PMID- 9603032
TI  - Modeling of recombinant yeast cells: reduction of phase space.
AB  - The mechanism of starch fermentation by recombinant Saccharomyces cerevisiae in
      batch reactor is studied. Experiments were carried in the presence and absence of
      oxygen, with different initial starch concentrations. A variety of data
      concerning biotic and abiotic phases are collected. Nonlinear data analysis
      techniques are used to determine the block diagram of the system under study.
      Data analysis and processing reported here, are believed to form a basis in
      further work in structured modeling of biological systems, recombinant yeast
      cultures in particular.

PMID- 9603033
TI  - Synovial tissues collected from rheumatoid patients undergoing total joint
      arthroplasty express markers for acute inflammation.
AB  - Rheumatoid arthritis is an autoimmune disease that causes inflammation mainly in
      synovial tissues. RA manifests as a chronic polyarthritis with intermittent acute
      inflammatory episodes. The inflammatory sites are characterized by infiltration
      of activated lymphocytes and macrophages into the synovial membrane, and the
      proliferation of synovial cells. The local production of a number of cytokines by
      proliferative synovial cells as well as by infiltrating cells appears to account
      for many of the pathological and clinical manifestations in rheumatoid arthritis.
      Tissues were collected from twelve RA patients undergoing joint replacement
      surgery. The synovium was collected and the cell types were identified, and
      markers for chronic and acute inflammatory mediators were measured. The cells
      types found in the synovium are capable of secreting cytokines which are capable
      of both acute inflammation (IL-1, IL-6, IL-8, MCP-1 and TNF), as well as chronic
      inflammation (IL-2, IL-10, and IL-4). The results obtained showed that the
      macrophages-derived acute inflammatory cytokines (IL-1, IL-6 and IL-8) were
      easily detected at levels of 22.6 +/- 12 pg/mg protein; 48.5 +/- 42 pg/mg
      protein, and 76 +/- 31 pg/mg protein; respectively. T-cell derived chronic
      inflammation cytokines (IL-2, IL-4 and IL-10) were rarely detected. Retrieved
      tissues that immunostained positive for IL-6, IL-1 and IL-8 also is suggestive of
      an acute inflammatory response. The results clearly demonstrate that the acute
      response may be responsible for the subsequent need for joint arthroplasties.

PMID- 9603034
TI  - Modeling and optimising alcohol production by fermentation of dextrose-xylose
      mixed feed using a fluorosensor.
AB  - Dextrose with differing amounts of xylose (mixed substrate medium) has been
      fermented at 28 degree Celsius with sacchromyces cerevisiae (Baker's Yeast) as
      seeding. The progress of the reaction was recorded by measuring the fluorescent
      signal due to intracellular reduced nicotinamide adenine di nucleotide (NADH)
      present in the cells with a Dr. Ingold (Switzerland) fluorosensor which has an
      excitation wavelength of 360 nm and measurement wavelength of 450 nm. The
      concentration of xylose in the xylose-dextrose feed was varied from 0.7% to 5.0%
      by weight. The optimum concentration of xylose at which the production of alcohol
      was a maximum was found to be 3.4 percent xylose. The fluorescent voltage data
      for different concentration of xylose fitted a first order model with an average
      absolute deviation of less than one percent. Development of this model is useful
      in design of model predictive controllers.

PMID- 9603035
TI  - Development of a microcomputer-based system to monitor healing from injury.
AB  - It is well documented that induction of electric current in bone not only
      prevents the bone loss of functional disuse, but also induces new bone formation.
      Moreover, the literature suggests that the skeletal response is optimal at a
      distinct frequency range 10-30 Hz. Indeed, even at peak strains, well below those
      typical of habitual physiological loading, applications of 30 Hz were shown to be
      osteogenic. This evidence supports the concept that inducing even very low
      strains may generate an effective osteogenic stimulus, provided that they are
      induced at optimal frequency (10 to 30 Hz). Bone appears to respond with greater
      selectivity and sensitivity to this frequency range of electrical stimulation.
      Inducing insulin-like growth factors, which are negatively charged, will provide
      the required electrical stimulus. Traditionally, the progression of the cellular
      events during trauma is normally followed by x-ray to determine a healing rate.
      Frequent use of this method can result in serious side effects to the vital and
      reproductive organs. The objective of this study is to develop a microcomputer
      based system to monitor the cellular events associated with healing. The system
      is capable of transmitting an electrical signal directly to the site of injury to
      improve the healing process and to monitor the progress of osteogenesis. The
      system consists of a base unit and implanted units. One implanted unit will be
      inserted in the femur with induced trauma and the other implant will be in the
      control femur. The base unit will transmit low frequency electromagnetic waves to
      the implanted units as well as receive periodic information about the ion
      movement in both femurs.

PMID- 9603036
TI  - A personal digital assistant for determination of fluid needs for burn patients.
AB  - In most instances, the treatment of major burn victims begins in the emergency
      room of the hospital closest to the accident site. It can be assumed that the
      emergency room personnel in most hospitals rarely see patients with major burns.
      Thus, their experience with burn fluid resuscitation is often limited. Yet it is
      critical that primary early treatment of burn injury with fluid resuscitation
      begin before the patient is admitted locally or transferred to a burn unit. To
      assist these individuals a fluid resuscitation calculation application has been
      developed to run on a hand-held personal digital assistant (Palm Pilot). This
      hand-held application is meant to assist in emergency situations where time is
      short, thoughtful computation is not possible, and a quick determination of fluid
      replacement therapy is important for the survival of the patient.

PMID- 9603037
TI  - Photorealistic speech agents and facially expressive robots.
AB  - In an ideal human-computer interface, the computer would be able to understand
      and use modalities such as speech, hearing, facial gestures and body language in
      as realistic and natural a manner as a human. This paper discusses two kinds of
      computer-to-human interaction techniques which involve computerizea facial
      gestures: the first is the graphics representation of the human face projected on
      a video display; the second is the physical embodiment of facial expressions
      using an android robot. These simulated facial gestures may be accompanied by
      computerized speech synthesis, voice recognition capability or machine vision for
      recognition of the facial expressions of the human viewer. The author reviews
      both major techniques, then discusses current and proposed applications of this
      methodology.

PMID- 9603038
TI  - Considerations for developing a clinical capnogram monitoring system.
AB  - Clinical monitoring and diagnostic systems may require the analysis of multiple
      physiologic signals to generate a diagnosis. The complexity of these systems is
      formidable for at least two reasons: clinical physiologic signals are noisy, and
      systems built around multiple signals may fail when any single signal is absent.
      In view of these limitations, we have been developing a clinical respiratory CO2
      waveform (capnogram) diagnostic system. The purpose of this system is to develop
      a differential diagnosis from a single signal for subsequent evaluation within
      the context of multiple single-signals. This paper will review the development
      issues which we have been confronting, and discuss the tools and methods which
      have been successful.

PMID- 9603039
TI  - Distributed neural networks for biomedical research.
AB  - To facilitate the application of neural networks in bio-medical sciences, we have
      developed a new client-server neural network concept that enhances user operation
      and reduces processing time. The client component allows users to enter all
      information required to create and control a complete neural network project. The
      server component provides the actual tools for neural network development. The
      server is able to distribute the burden of neural network processing among remote
      machines, if available. To date, the system has been applied successfully to
      problems in the of chromosome recognition and horse gait analysis domains.

PMID- 9603040
TI  - Saccade derivative filters and their clinical implications.
AB  - A saccade model is used to evaluate the accuracy of three derivative algorithms,
      the two-point central difference derivative filter, band-limited derivative
      filter and median derivative filter. Noise contaminated saccade simulations are
      used to compare the known velocity and acceleration waveforms with estimates from
      each of the three algorithms. The median derivative filter, a nonlinear
      differentiating digital filter, provides the best velocity estimates from an eye
      position signal. This filter has no impulse response function, eliminates Gibb's
      phenomena evident in all linear filters, and is easy to implement.

PMID- 9603041
TI  - Mechanical response of an artery using a standard nonlinear solid.
AB  - INTRODUCTION: The stress and deformation in an artery are determined from an
      axisymmetric analysis of thick-walled cylinder with a time-dependent internal
      pressure. The purpose is to understand how different constitutive, loading, and
      geometric conditions affect the stress and deformation state within the artery.
      MATERIALS AND METHODS: The equilibrium, compatibility, and constitutive equations
      are applied at N discretized points in the arterial wall, in an efficient scheme
      using Mathcad software on a desktop computer. The constitutive equations are a
      modification to a standard linear solid, so that one of the linear elements is
      nonlinear, and so that the 3-D response is anisotropic and dissipates energy only
      under deviatoric (shearing) stress states. Solution at each successive time
      increment requires inversion of a 6N by 6N matrix. RESULTS: The model reproduces
      experimental stress relaxation data with a correlation coefficient of 0.985 and
      can reproduce quasi-static stress strain data with equal accuracy. Features such
      as conditioning of the tissue are understood in terms of the time-dependent
      properties of the tissue. CONCLUSION: The program can produce transient and
      steady-state responses that closely mimic tissue response. The analysis allows
      for quick and stable determination of the stress and strain states for a variety
      of loading conditions.

PMID- 9603042
TI  - An elbow joint movement control model with visual feedback.
AB  - A motor program generator control model is proposed to simulate neuromuscular
      control. Three muscles (Biceps, Triceps, Brachialis) driving elbow joint flexion
      in a plane are simulated by integrating their nonlinear dynamic property and
      spinal neural circuitry. The motor descending commands are described by a visual
      feedback signal from the joint and an excitation signal for the motor neuron
      pool. The visual feedback signal mimics the gamma command whereas the excitation
      signal mimics another descending co-activation command. The gamma command is
      expressed as the output of a PID controller with the visual feedback error signal
      as the input. The gamma command and the motoneuron pool background activity are
      the inputs to the motoneuron pool model coupled with the Renshaw cell recurrent
      inhibitions. The output of the motoneuron pool model mimics the alpha command
      feeding directly to the muscle dynamics. A movement is produced by reducing the
      error signal between goal position and actual position and altering excitation
      signal properly. The simulation results show that a burst pattern of excitation
      signal and a PID controller can accurately trace the terminal goal and generate a
      smooth movement with a bell shaped velocity profile. The muscle activation
      signals have the characteristic similar to the smoothed EMG. Changing different
      parameters of the PID can cause the same effects as the stimulus pulse intensity
      or duration modulation.

PMID- 9603043
TI  - The development of a hybrid analog/digital retinal surgical laser system.
AB  - In the last few years the progress made in producing an integrated automated
      retinal surgical laser system has grown tremendously. Two different techniques
      have been developed in parallel: an analog and a digital system. Both the analog
      and digital systems are capable of tracking the retina while precisely placing
      lesions in desired locations. However, each system has its unique advantages and
      disadvantages to an automated surgical system. Current work has been conducted to
      integrate these two techniques to take full advantage of their unique
      capabilities. The goal of this research is to successfully integrate the systems
      to provide a better retinal surgical treatment for those individuals affected by
      diabetes, retinal tears, and other eye disorders.

PMID- 9603044
TI  - Integration of analog and digital retinal tracking and coagulation subsystems.
AB  - Laser photocoagulation is used by ophthalmologists to treat retinal disorders
      such as diabetic retinopathy and retinal breaks and tears. Currently, the
      procedure is performed manually and suffers from several drawbacks: it often
      requires many clinical visits, it is very tedious for both patient and physician,
      the laser pointing accuracy and safety margin are limited by a combination of the
      physician's manual dexterity and the patient's ability to hold their eye still,
      and there is a wide variability in retinal tissue absorption parameters. This
      paper describes progress in developing a computer-assisted robotic laser system
      that will rapidly and safely place multiple therapeutic lesions at desired
      locations on the retina in a few seconds.

PMID- 9603045
TI  - Laser therapy by noncoherent light field of radiation.
AB  - Conducted researches on study of interaction of radiation with blood have shown,
      that the interaction is the most effective for light with wavelengths in the
      range of 600-1000 nm that corresponds to the minimum absorption factor of the
      whole blood. Calculations show, that at interaction of radiation with blood
      considerably grows effective (electronic) temperature of biological environment,
      that results in sharp increase of speed of biochemical reactions. The absence of
      necessity of application of laser radiation coherence in lasertherapy permits to
      create high efficient noncoherent sources of light on the basis of the GaALAs(Zn)
      crystals, radiating with two maxima of wavelengths 675 and 900 nm. The radiation
      spectrum of GaALAs(Zn) crystals falls in the most favourable area of a blood
      absorption spectrum.

PMID- 9603046
TI  - Sources of error in monitoring high speed testing of vascular grafts.
AB  - Mechanical compliance issues are increasingly important in the design, testing,
      and manufacture of vascular grafts. This has to do with the observed relationship
      between long-term patency of implanted grafts and accurate compliance matching of
      those devices with the recipient natural vessels. Another important concern in
      this type of investigation has to do with the use of mock arteries during the
      testing of implantable medical products such as intravascular stents,
      stent/grafts, etc. At issue here are not simply the techniques used to monitor
      the static compliance of the vessels, but the dynamic properties which are in
      effect during the in vivo utilization of these devices. Perhaps of even more
      importance is understanding the high speed dynamic properties of these vessels so
      that a proper and reliable high-speed durability experiment might be designed.
      There is a natural tendency to adopt procedures that monitor outside dimensions
      of the graft or artery. The theoretical problem with this approach is the fact
      that compliance matching is a phenomenon associated with the inner lumen of the
      tube, whether it is hydrodynamic considerations in vascular graft testing or
      loading considerations in stent testing. Optical techniques such as lasers and
      ultrasound are encumbered by two physical motion phenomena unique to this
      approach. The first is simple jumping or movement of the tube due to vibrations.
      This problem can be overcome by high sampling rates. The second is more
      problematic and results in lengthening of the tube that has longitudinal as well
      as radial compliance. Both quantitative and qualitative examples will be
      examined. A comprehensive understanding of the sources of error encountered in
      various monitoring techniques is reviewed. These techniques will include lasers,
      dynamic internal compliance, ultrasound, and cantilevered beams.

PMID- 9603047
TI  - Heart rate variability during exercise in the horse.
AB  - High heart rate variability (HRV) has been associated with more efficient
      autonomic control, allowing more responsivity and sensitivity to changing
      environmental demands. Previous results from spectral analysis of interbeat
      intervals of equine heart rate (HR) indicated increased HRV, reflecting more
      effective vagal control of the heart. This study focuses on characterizing equine
      HR and HRV during increasing then decreasing physical demand. A non-invasive
      ambulatory monitoring system continuously records HR and HRV as horses exercise
      on a high speed equine treadmill at increasing then decreasing workloads. After a
      5 minute baseline, the horses walk, then trot, then canter or trot fast, return
      to the slower trot, then walk, and then remain quiet for a 5 minute recovery
      period. Results indicate a decrease of HRV and large individual differences in
      parasympathetic activity during exercise. Resulting patterns of HR fluctuation
      indicate a nonlinear dynamical approach may describe the task responses more
      completely than the more traditional models.

PMID- 9603048
TI  - Thermoregulation and cardiac variability: a time-frequency analysis.
AB  - High heart rate variability (HRV) has been associated with more efficient
      autonomic control, allowing more responsivity and sensitivity to changing
      environmental demands. A number of specific periodicities have been identified in
      the spectra of cardiac time series. A high frequency component related to
      respiratory sinus arrhythmia, a low frequency component related to blood pressure
      variability, and a very low frequency component thought to reflect
      thermoregulation have been reported in the literature. However, the source of the
      very low frequency component has not been extensively investigated in humans
      using non-invasive methods and analytic techniques that do not rely upon
      stationarity. We investigated HRV in response to both hot and cold thermal
      challenge in healthy adults using time-frequency analysis. This analytic
      technique does not rely upon signal stationarity. The results suggest that very
      low frequency power may reflect thermoregulation to ambient temperature changes.
      Implications for prediction of cardiac events are discussed.

PMID- 9603049
TI  - Higher order regularization techniques for inverse electrocardiography.
AB  - We have previously presented the generalized eigensystem (GES) approach as an
      alternative to truncated singular value decomposition and zero order Tikhonov
      regularization methods for the ill-conditioned inverse problem of
      electrocardiography. In this paper we extend our comparison of GES with Tikhonov
      regularization utilizing higher order regularizers applied to a realistic
      heart/torso geometry with measured epicardial and body surface potentials.
      Utilizing higher order regularizers the results from Tikhonov regularization more
      closely match those of the GES techniques.

PMID- 9603050
TI  - Hemodynamic consequences of replacing the aorta by vascular grafts simulated in a
      mathematical model.
AB  - OBJECTIVE: Replacing parts of the aorta by a noncompliant vascular prosthesis
      results in marked alterations of the aortic input impedance and influences
      arterial hemodynamics. We propose a mathematical model of circulation able to
      predict hemodynamic changes after simulation of vascular grafting. METHODS: Using
      a mathematical 128-branch model of the human arterial system a digitized aortic
      flow wave was chosen as the input signal to this system. After determination of
      the modules of elasticity of native vascular tissue and customary prostheses in
      technical experiments, replacement of any part of the aorta with a prosthesis was
      simulated by increasing the elasticity in the parts desired. RESULTS: During
      control conditions, the model displayed a physiologic distribution of flow and
      pressure waves throughout the arterial system. Simulated replacement of the aorta
      resulted in an increase of pressure amplitude and a partial loss of the aortic
      "Windkessel" function. Calculation of the aortic input impedance showed an
      increase of the characteristic impedance, while the peripheral resistance
      remained unaltered. CONCLUSION: This mathematical model of the arterial
      circulation proves to be useful to simulate hemodynamic changes after
      implantation of vascular grafts. The results of the model analysis are consistent
      with previous work done in experimental setups.

PMID- 9603051
TI  - Description of the ventriculoarterial interaction dynamics using recurrence plot
      strategies.
AB  - OBJECTIVE: The classical description of ventriculoarterial coupling by
      calculating the ratio between the effective arterial elastance Ea to the end
      systolic elastance Ees does not give insight into the underlying dynamics of the
      interaction between left-ventricular pressure (LVP) and aortic pressure (AOP) and
      flow (AOF). The aim of this study was to introduce a state space representation
      for the ventriculoarterial coupling and to quantify changes of the coupling
      state. METHODS: A ventriculoarterial state space orbit VAO was defined to be
      dependent on three variables: VAO = [LVP(t), AOP(t + delta t), AOF(t + delta t)].
      Changes in the coupling effect directly or indirectly on the time series of these
      parameters. They reflect the actual state of the cardiovascular system. The time
      delay delta t between the LVP and the aortic signals takes respect to the short
      delay between the heart action and the resulting waves in the arterial tree. The
      recurrence map of the VAO(i) (i = 1 .. N, N = number of points) is constructed by
      plotting the index i of every single point on the orbit (x-axis) against the
      indices of his 10 nearest neighbors (y-axis) in distance. The data were recorded
      in 9 anaesthetized pigs with a sample frequency of 512 Hz over a period of 6
      seconds using piezoelectric pressure sensors and a Doppler flowmeter. A control
      condition was compared to a total occlusion of the descending aorta as a strong
      artificial disturbance of ventriculoarterial interaction. The nonlinear
      parameters percent recurrence, percent determinism and the entropy were
      calculated from the plot. RESULTS: Periodic crossing points and forbidden zones
      in all plots identify the nonlinear character of the chosen variables. The
      recurrent patterns are less rigid for control conditions than for total
      occlusion. Entropy (2.3% rise) and determinism (24% rise) are significantly (p <
      0.003) increased. Total aortic occlusion leads to more complex time correlation
      patterns. CONCLUSIONS: These results may reflect the loss of an ideal coupling
      state leading to a more complex deterministic behavior of the overall regulatory
      system. Because recurrence plots do not impose rigid constraints on data set
      size, stationarity, or statistical distribution, we hypothesize that this
      technique might be useful to describe the nonlinear dynamics between left
      ventricle and arterial system.

PMID- 9603052
TI  - Simulation of human circulation at cardiopulmonary bypass.
AB  - This article describes a simulation model of the human circulatory system under
      extracorporeal circulation. The model is supposed to enable the design of a
      controller for heart-lung-machines, and to perform simulations of the
      controllers' behaviour. The controller should be able to control extracorporeal
      circulation based on the oxygen supply to individual organs. The model contains
      all important control mechanisms in the human circulation that maintain
      hemodynamics, and the influences of extracorporeal circulation to them. We
      considered the renin-angiotensin-system, the arterial local autoregulation and
      the autonomic nervous system. The behaviour of the most important hormone levels
      is reproduced. Furthermore, hemodynamics in the arterial tree is modeled with
      locally distributed pressure and flow parameters in 128 vessel segments to gain
      knowledge about the oxygen supply position of single internal organs. The
      influences of the special circumstances of an operation under extracorporeal
      circulation such as anesthesia or hypothermia are implemented in the model.
      Simulation results show that our model describes the behaviour of human
      circulation detailed enough to validate the designed controllers.

PMID- 9603053
TI  - A WEB based approach in biomedical engineering design education.
AB  - As part of the accreditation process for university engineering programs,
      students are required to complete a minimum number of design credits in their
      course of study, typically at the senior level. Many call this the capstone
      course. Engineering design is a course or series of courses that bring together
      concepts and principles that students learn in their field of study--it involves
      the integration and extension of material learned in their major toward a
      specific project. Most often, the student is exposed to system-wide analysis,
      critique and evaluation for the first time. Design is an iterative, decision
      making process in which the student optimally applies previously learned material
      to meet a stated objective. At the University of Connecticut, students work in
      teams of 3-4 members and work on externally sponsored projects. To facilitate
      working with sponsors, a WEB based approach is used for reporting the progress on
      projects. Students are responsible for creating their own WEB sites that support
      both html and pdf formats. Students provide the following deliverables: weekly
      progress reports, project statement, specifications, project proposal, interim
      report, and final report. A senior design homepage also provides links to data
      books and other resources for use by students. We are also planning distance
      learning experiences between two campuses so students can work on projects that
      involve the use of video conferencing.

PMID- 9603054
TI  - An application of digital network technology to medical image management.
AB  - With the advent of network technology, there is considerable interest within the
      medical community to manage the storage and distribution of medical images by
      digital means. Higher workflow efficiency leading to better patient care is one
      of the commonly cited outcomes [1,2]. However, due to the size of medical image
      files and the unique requirements in detail and resolution, medical image
      management poses special challenges. Storage requirements are usually large,
      which implies expenses or investment costs make digital networking projects
      financially out of reach for many clinical institutions. New advances in network
      technology and telecommunication, in conjunction with the decreasing cost in
      computer devices, have made digital image management achievable. In our
      institution, we have recently completed a pilot project to distribute medical
      images both within the physical confines of the clinical enterprise as well as
      outside the medical center campus. The design concept and the configuration of a
      comprehensive digital image network is described in this report.

PMID- 9603055
TI  - Data mining issues for improved birth outcomes.
AB  - Issues obstructing progress in data mining for improved health outcomes include
      data quality problems, data redundancy, data inconsistency, repeated measures,
      temporal (time-contextual) measures, and data volume. Related issues involve
      theoretical and technical problems involving uncertainty management, missing data
      and missing values, and matching appropriate data mining techniques to patient
      data sets. Results of data mining research in progress are reported for Duke
      University's perinatal database that contains nearly a decade of clinical patient
      data, 71,753 database (patient) records and 4-5000 variables per patient.

PMID- 9603056
TI  - Special considerations for WEB-based clinical database applications.
AB  - The Hospital Information System at the University of Missouri-Columbia Veterinary
      Medical Teaching Hospital is implementing a web-based interface to the existing
      Hospital Information System. The "stateless" nature of HTML forms introduces a
      number of special considerations that, though not immediately obvious,
      nevertheless apply to any multi-user database application. Problems including
      identifying sessions and users, dealing with abandoned sessions or use of the
      "Back" arrow on the browser, record locking across multiple forms, state
      variables, and flow through "utility" forms. General solutions to each of these
      problems have been devised and are presented here.

PMID- 9603057
TI  - Bringing a WEB-based interface to a hospital information system.
AB  - The Hospital Information System at the MU Veterinary Medical Teaching Hospital is
      a "home-grown" system written in MUMPS. The system has a "roll-and-scroll" user
      interface typical of terminal based systems from the 1970s and early 1980s. We
      are now introducing a new user interface that uses World Wide Web technology
      (HTML forms). Computers connected to the hospital's intranet can access the
      hospital system using the Web browser of the user's choice. The new user
      interface can run in parallel with the older interface (even on the same
      computer), and uses the same underlying database. This allows a smooth migration
      to the new interface which minimizes both user and programmer anguish. User
      acceptance has been good, and the ease and speed of development has been very
      promising.

PMID- 9603058
TI  - A review of localized tomography.
AB  - Localized computed tomography is the field of reconstructing an image of a
      portion of the internal structure of an object from an incomplete set of
      projections. Standard computed tomographic techniques require a full set of
      projections even when only a small portion of the object is of interest. The
      first localized tomographic technique was developed in the field of non
      destructive testing in 1981 by Soviet scientists. Since this initial work
      numerous other researchers have advanced the field of localized tomography in
      theoretical and applied areas. This paper reviews the diverse localized computed
      tomography field.

PMID- 9603059
TI  - Homologue matching using the Choquet integral.
AB  - Automated Giemsa-banded chromosome image research has been largely restricted to
      classification schemes associated with isolated chromosomes within metaphase
      spreads. In normal human metaphase spreads, there are 46 chromosomes occurring in
      homologous pairs for the autosomal classes, 1-22, and X chromosome for females.
      For optimizing automated human chromosome image analysis, many existing
      techniques assume cell normalcy. With many genetic abnormalities directly linked
      to structural and numerical aberrations of chromosomes within the metaphase
      spread, the two chromosome per class assumption may not be appropriate for
      anomaly analysis. At the University of Missouri, a data-driven homologue matching
      approach has been developed to identify all normal chromosomes within a metaphase
      spread from a selected class. Chromosome assignment to a specific class is
      initially based on neural networks, followed by banding pattern and centromeric
      index criteria checking, and concluding with homologue matching utilizing a
      density profile-based classifier, a shape profile-based classifier, and a binary
      band profile-based classifier. Based on preliminary results for the profile-based
      classifiers assigning chromosome 17, the Choquet integral is presented as an
      extension to the homologue matching approach. Experimental results are presented
      comparing the extended homologue matching approach to the transportation
      algorithm for identifying chromosome 21 within normal metaphase spreads.

PMID- 9603060
TI  - Automatic determination of patellofemoral kinematic parameters through X-ray
      image processing.
AB  - Examination of plain Merchant-view X-rays of the patellofemoral joint is often
      used to diagnose patellofemoral joint malalignment and to qualify the pathology.
      As digital image processing becomes more widespread, an image processing
      algorithm is being developed for medical personnel to easily display, manipulate
      and analyze digitized plain Merchant-view X-ray films on personal computers. The
      method provides measurement of the kinematic parameters: sulcus angle (SA),
      patellofemoral congruence angle (PFC), lateral patellar angle (LPA), patellar
      rotation angle (PR), and lateral patellar displacement (LPD). Smooth edges of the
      patella and the femur are obtained by using image enhancement, edge detection and
      morphological thinning techniques based on the thresholds chosen manually for
      boundary detection. Six landmarks for determining the kinematic parameters are
      marked automatically on the edges of patella and femur. Parameter measurements
      for twelve X-ray films of six patients are calculated for analysis and comparison
      with hand calculated parameters. The goal is develop an algorithm that can
      evaluate the geometry of the patellofemoral joint, and is cost effective.

PMID- 9603061
TI  - Scapulothoracic rhythm in normal male volunteers.
AB  - Dynamic pattern of Scapulothoracic rhythm during arm abduction in scapular plane
      is studied using computer-imaging technique. Aim of the study is to produce a
      reproducible and reliable way of calculating the scapular movement and
      glenohumeral movement using least possible roentgenographic exposure. Moving X
      ray screening picture of the shoulder joint is analysed using video capture
      computer programme and the images at different degrees of abduction are then
      analysed for scapular movement using computer aided designer and drafting
      software. Results were comparable to the authoritative shoulder analysis carried
      out in the past, the difference of radiation exposure, approximately 10 times
      less.

PMID- 9603062
TI  - Argon plasma electrosurgical coagulation.
AB  - Both argon plasma electrosurgical coagulation (APEC) and conventional
      electrosurgical fulguration (CEF) apply electrosurgical energy to the target
      tissue through a plasma. Presented here is a detailed examination of this
      process. Consideration of the fundamental processes and characteristics of
      plasmas and the various parameters they are dependent upon illuminates and
      explains the similarities and differences between APEC and CEF. Both APEC and CEF
      provide non-contact and self-limiting coagulation. The electrical and chemical
      differences between air and argon are, however, manifested in very different
      plasmas and tissue effects. Chief among these are the much greater working
      distance achievable with APEC, its uniformity of tissue effect and the softness
      of the eschar it produces. The variance of these characteristics and effects as
      functions of parameters under the control of the surgeon is examined both
      theoretically and experimentally. Measurements of tissue damage show that they
      vary with working distance, generator power, and time more controllably and
      predictably with APEC than with CEF. CEF is shown to have application for pin
      point coagulation while APEC excels at controlled coagulation of larger areas
      with greater uniformity of depth.

PMID- 9603063
TI  - Stability analysis of a controller for a high power ultrasonic actuator.
AB  - High power ultrasonic transducers for medical surgery require closed loop
      regulation of operating frequency and amplitude. This is a tutorial design paper
      which provides a description of the fundamental component properties and the
      criteria which are required to drive a power ultrasonic transducer. In addition,
      a classical root locus system analysis of the regulator servo in conjunction with
      requirements for idealizing individual blocks is also provided.

PMID- 9603064
TI  - Intercostal nerve nerve neuroma (PNS) implantation in spinal cord anastomosis
      bridging spinal cord transection--enhancement of central neurons (CNS) axonal
      regeneration.
AB  - The enhancement of axonal regeneration in the spinal cord transection is shown by
      implanting intercostal nerve neuroma with origin cephalic to spinal cord
      transection site. The nerve is implanted in the distal spinal cord near the
      transection site. The intercostal nerve peripheral portion is anchored in the
      distal spinal cord using a plasma clot suture. 2,3,4 Regeneration of (CNS) axons
      and (PNS) axons in the spinal cord transaction lesion demands care,
      rehabilitation, no infections, and maintenance of normal body functions. After a
      period of repair and rehabilitation "reflex" standing and walking developed in 26
      mature female dogs. Surgical section of the implanted nerve resulted in loss of
      standing and reflex walking and return to a paraplegic condition. 2,3,4,5
      Stimulation of the motor cortex and implanted intercostal nerve resulted in
      movements of the hind limbs of the standing and reflex walking dogs all having
      cord transection and intercostal nerve neuroma implantation. 2,3,4,5 The neuroma
      generates spontaneous electrical activity as unit discharges similar to seizure
      and epleptic activity. This activity has a role in spinal cord lesions in the
      induction of regeneration of axonal sprouting. 1,2,3,4,12,13,15

PMID- 9603065
TI  - Repair, reconstruction, regeneration and rehabilitation strategies to spinal cord
      injury.
AB  - The structural changes seen in the transected spinal cord followed by
      transplantation of the distal ends (neuroma) of intercostal nerve inserted into
      the spinal cord proximal and distal to the transection lesion site. This
      activates CNS axonal regeneration. 2,3,4 These changes refer to the plasticity in
      the nervous system following damage to the spinal cord. There is regeneration and
      growth and synapotogenesis and remodeling of synaptic connections, development of
      reflex activity in the denervated cord. Nerve growth factors and neurotrophic
      factors sustain and maintain a degree of functional integrity of structural
      neural circuitry. 2,3,4,13 The end result is standing, stepping, and reflex
      walking in 28 female mature dogs. 2,3,4,5 Electrical stimulation of the
      anastomosed intercostal nerves resulted in hind limb movements and recording of
      the electromyograms of the contracting muscles. Twenty-six control dogs and
      animals with behavioral depression are unable to follow rehabilitative procedures
      developed muscle atrophy, ankylosis of joints, decrease in bone density, decrease
      in reflex activity of the spinal cord distal to the transection. 2,3,4,5

PMID- 9603066
TI  - Impact of body size on women's military obstacle course performance.
AB  - The United States Military Academy uses an Indoor Obstacle Course Test (IOCT) to
      assess military-relevant physical fitness. There are both anaerobic and aerobic
      fitness components to this test. Recent attention has been focused on the
      apparent difficulty of heavier female cadets to succeed on the IOCT. The purpose
      of this study was to use allometric scaling to examine the effects of body weight
      (BW), fat-free mass (FFM), percent body fat (%BF), and fat mass (FM) on IOCT
      performance for female cadets. The sample included 38 female cadets who
      successfully completed the IOCT. Performance was defined by the time, T, to
      complete the entire course. FFM was determined via a three-site skinfold test.
      Allometric modeling was used to determine the exponent in the following index:
      T*BW2 such that the independent contributions of body size are partialled out.
      This analysis was used for all four independent variables simply by substituting
      BW with the other independent variables. The following exponents were found to be
      significant (p < 0.05): 0.45 +/- 0.13 for %BF and 0.24 +/- 0.12 for FM indicating
      that these independent variables play a significant role in female performance on
      the IOCT. For example, if a female cadet could decrease her %BF from 20% to 18%,
      which would be decrement of ten percent, then her estimated decrease in IOCT time
      is 4%. In addition, a trend (p = 0.06) was found for FFM meaning that as FFM
      increases, T decreases. We conclude that, among USMA female cadets, small
      decreases in %BF may be significantly advantageous to IOCT performance.

PMID- 9603067
TI  - Development of an underwater weighing system for determining body composition.
AB  - A system was developed to reduce some of the difficulties associated with
      hydrostatic (underwater) weighing, specifically the need for complete exhalation
      and the subjective approximation of weighing scale measurements. The exhalation
      portion of the weighing protocol is particularly difficult for many disabled
      individuals and has contributed to the lack of available body composition
      information for this population. The components of our system include a computer
      system, load cell, spirometer, breathing tube, logic and signal conditioning
      circuitry specially constructed for this system, and a software package developed
      for this project. In a preliminary test, the body fat percentages of fourteen
      subjects (six males and eight females, ages 21-32 years) were determined both
      with the standard method and with our system. A correlation of r = 0.967 was
      found between the two methods, with our system's precision ranging from 1.0 to
      1.3 body fat percentage points. The system could be used, for example, in
      developing a database for monitoring an individual's fitness or for making
      comparisons between groups (such as athlete to non-athlete).

PMID- 9603068
TI  - Computational contact analysis of joint congruency.
AB  - Joint contact analysis of the musculoskeletal system is an important biomedical
      research topic due to its significant clinical relevance. In this research, the
      finite element method was used to study the effect of joint congruencies (various
      radii, R1 and R2), contact area (angles theta), and contact stresses of articular
      joints (the far-field applied pressure, P = 10,000 Pa). In total, 12 joint
      congruency cases, ranging from R1/R2 = 100% (congruent) to R1/R2 = -100% (highly
      incongruent) were analyzed. The linear finite element (quasi-static/equilibrium)
      results show that peak contact stress delta r of a congruent joint (R1 = R2 theta
      = 90 degrees) is -13,068 Pa. However, with a slight change of joint congruency
      (R1/R2 = 99.7%), the contact area decreases dramatically (theta = 30 degrees) and
      leads to a much higher concentrated contact stress, delta r = -27,894 Pa. When
      R1/R2 = -100%, the finite element result shows that the contact region is only
      theta = 3 degrees and the associate peak contact stress delta r is -229,943 Pa.

PMID- 9603069
TI  - Differing effects of two-week suspension on male and female mouse bone
      metabolism.
AB  - The effects of suspension on bone histomorphometry during the first and second
      week of tail suspension are compared for male and female mice of the common
      inbred strain, the C57BL/6J. In male mice, significant changes in bone formation
      rate (BFR) were largely confined to the endocortical perimeter. BFR along the
      endocortical mid-diaphysis in the femora of suspended male mice was reduced 54.1%
      and 55.6% for the first and second week, respectively. In female mice, however,
      measured metabolic changes due to suspension occurred along the periosteal
      perimeter, where there was a decrease in BFR of 58.3% for the first week and
      60.9% for the second. The notable difference in the bone perimeter affected by
      suspension observed in male and female mice indicates a difference in the
      metabolic control of bone development in male and female C57BL/6J mice. More
      importantly, this may indicate a sex-based difference in preserving structural
      properties in the response of the skeleton to unloading.

PMID- 9603070
TI  - Therapeutic efficacy of corticosteroid injections in the acromioclavicular joint.
AB  - There is debate among orthopaedists about the efficacy of steroid therapy to
      treat painful joints. Using an uncontrolled, retrospective study, we examined the
      usefulness of local corticosteroid injections in thirty-one patients (twenty-four
      men, seven women) with isolated AC joint arthropathy. No patients had signs of
      impingement or rotator cuff disease. All injections were performed using a
      standardized technique with each patient receiving 1cc Celestone/Soluspan or
      Dexamethasone and 2cc Lidocaine. At an average follow-up of nineteen months,
      patients were asked to answer questions regarding activity of daily living,
      according to the American Shoulder and Elbow Surgeons (ASES) format, average
      level of pain, length of pain relief from steroid injection, and time to return
      to full activity. Four patients could not be contacted for follow-up questions
      and, therefore, were excluded from the study leaving twenty-seven patients. Pain
      and function improved in twenty-five of twenty-seven (93%) patients after
      injection. Mean duration of improvement was twenty days (range, two hours to
      three months). Two patients reported continued relief at 1.5 and two years after
      injection. Due to persistent, insidious pain, eighteen of twenty-seven (67%)
      patients underwent distal clavicle excision an average of four months after
      injection. Overall, twenty-two of twenty-seven (81%) patients failed to obtain
      long-term relief from the injection. The results of this study suggest that the
      administration of local corticosteroids into the AC joint may provide short-term
      pain relief, but does not alter the natural progression of disease.

PMID- 9603071
TI  - Positioning errors produced by persons with knee joint disease when vision is
      occluded.
AB  - This study examined the effect of occluding static vision on the ability of
      persons with knee joint disease and impaired position sense to actively reproduce
      knee angles in a one-legged standing position. The subjects, six women with knee
      joint disease, ages 54-75 years each performed a series of two knee repositioning
      tasks in the ranges of 20-40 degrees flexion on two different occasions, both
      with, and without visual feedback. On each occasion, the leg was marked with
      reflective markers and the resultant sagittal plane knee angles were
      photographed. Whilst the absolute differences between the criterion and the
      matching knee angles calculated from these records showed vision to have an
      effect on positioning accuracy (p = 0.04), there were no differences in mean
      absolute constant errors between the two experimental paradigms, indicating
      similar perceptual judgment in memory. However, variability in performance tended
      to be greater when vision was occluded (p = 0.08). These findings suggest that
      while visual sources of information may play a minor role in the knee positioning
      bias towards target overestimation apparent in this group, supplementary visual
      cues may help to promote more consistent positioning performance.

PMID- 9603072
TI  - Probability of valid gait data acquisition using currently available force
      plates.
AB  - A major difficulty in using force plates for gait analysis is to have a foot fall
      completely on the instrument while not having the other foot in contact with the
      same device. This translates into more trials (and time) required to obtain valid
      data. In order to estimate the probability of a successful trial, which is
      related to the overall number of trials required, the dimensional relationships
      between force plate, foot and gait cycle were investigated. In particular, it was
      analyzed how the dimensions of the plate, the size of foot, the step length and
      width affect the probability of having a successful trial when acquiring one or
      two subsequent foot falls using one or two force plates respectively. The
      equations obtained can also be used to estimate the force plate dimensions that
      allow for the minimum number of trials for a specific group of subjects. To
      illustrate this approach, commercially available force plate sizes were
      statistically evaluated using gait data collected in recent years at The Ohio
      State University Gait Laboratory from patients with different pathologies. The
      force plate length maximizing the probability of a successful trial was
      identified for this specific population.

PMID- 9603073
TI  - Functional analysis of monocyte subsets in surgical sepsis.
AB  - BACKGROUND: Sepsis still remains a major cause of death after surgery. Impaired
      monocyte (Mphi) function and disruption of monocyte (Mphi/T-cell interaction were
      shown to be crucial for the development of septic complications in these
      patients. It was the objective of the study to assess more insights in Mphi
      behavior in surgical sepsis by means of analysis of Fc receptor- and human
      leukocyte antigen DR (HLA-DR) expression in Mphi subsets, and to evaluate the
      kinetics of these changes. METHODS: In a prospective study, 20 septic patients
      and 10 healthy control subjects were included. Peripheral Mphi were isolated on
      consecutive days after onset of sepsis, and FcR positive (FcR+) and negative (FcR
      ) subsets were separated by rosetting with antibody-coated human erythrocytes.
      Cell surface receptor expression and in vitro cytokine production were used to
      determine the clinical importance of these subsets. RESULTS: A significant
      monocytosis (3.5-fold; p < 0.01) and suppression of HLA-DR receptor expression
      (35%, p < 0.01) which correlate with sepsis severity and outcome could be
      demonstrated. There was a significant increase of FcR+ subsets in sepsis compared
      with control subjects (60% vs. 24%; p < 0.05). In vitro stimulation of Mphi
      subsets and peripheral blood mononuclear cells revealed suppressed interferon
      gamma synthesis (p < 0.05 up to 0.01) from day 1 to day 5, elevated neopterin
      release (p < 0.05) on day 14 and increased synthesis rates of proinflammatory
      cytokines (e.g., interleukin-1beta); p < 0.05) predominantly in FcR+ subsets.
      CONCLUSIONS: Sepsis results in a significant monocytosis and suppression of HLA
      DR receptor expression, which are correlating with sepsis severity and outcome. A
      significant shift toward FcR+ Mphi subsets can be found. This subpopulation
      resembles the previously described "angry macrophage" that is characterized by
      high proinflammatory cytokine synthesis and suppressed antigen presentation and
      that contributes to a disruption of adequate Mphi/T-cell interaction, rendering
      the host anergic toward opportunistic infections. The extend of HLA-DR
      suppression and the shift toward FcR+ Mphi might characterize a high risk patient
      subpopulation, which could benefit from immunomodulatory strategies.

PMID- 9603074
TI  - Granulocyte colony-stimulating factor improves host defense to resuscitated shock
      and polymicrobial sepsis without provoking generalized neutrophil-mediated
      damage.
AB  - BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) increases production
      and release of neutrophil precursors and activates multiple functions of
      circulating polymorphonuclear neutrophils (PMNs). G-CSF has therapeutic effects
      in many experimental models of sepsis; its actions with superimposed reperfusion
      insults are unknown. In traumatic conditions, G-CSF could exacerbate unregulated,
      PMN-dependent injury to otherwise normal host tissue or, it could partially
      reverse trauma-induced immune suppression, which may improve long-term outcome.
      This study tested whether stimulating PMN proliferation and function with G-CSF
      during recovery from trauma+sepsis potentiated reperfusion injury or whether it
      improved host defense. METHODS: Anesthetized swine were subjected to cecal
      ligation and incision, 35% hemorrhage, and 1 hr of hypotension. Resuscitation
      consisted of intravenous G-CSF (5 microg/kg) or placebo followed by shed blood
      and 40 mL/kg of lactated Ringer's solution. The control group received laparotomy
      only. G-CSF or placebo was given daily. Animals were killed at 4 days. Observers,
      blind to the protocol, graded autopsy samples for localization of infection and
      quality of abscess wall formation. Data included complete blood count,
      granulocyte oxidative burst after phorbol myristate acetate stimulation in vitro
      (GO2B), bronchoalveolar lavage (BAL) cell count, BAL noncellular protein,
      lipopolysaccharide-stimulated tumor necrosis factor production in whole blood in
      vitro (lipopolysaccharide-tumor necrosis factor), and lung tissue myeloperoxidase
      (MPO). RESULTS: Neutrophilia and localization of infection, were significantly
      improved by G-CSF. Variables altered by G-CSF, though not significantly, showed
      GO2B potential increased by 50%, lipopolysaccharide-tumor necrosis factor
      decreased by 50%, and improved survival versus placebo (100% vs. 70%). G-CSF did
      not increase lung MPO, BAL cell count, or BAL protein. Both arterial and venous
      O2 saturations were unaltered. CONCLUSIONS: Our data show that G-CSF initiated at
      the time of resuscitation reduced the sequelae of posttrauma sepsis by increasing
      PMN proliferation and function without potentiating PMN-mediated lung reperfusion
      injury.

PMID- 9603075
TI  - Immune responses of splenectomized trauma patients to the 23-valent pneumococcal
      polysaccharide vaccine at 1 versus 7 versus 14 days after splenectomy.
AB  - OBJECTIVES: Pneumococcal polysaccharide vaccine is given after emergency
      splenectomy for trauma to lessen the risk of overwhelming postsplenectomy sepsis.
      This study was undertaken to determine optimal timing of vaccine administration
      as determined by serum type-specific polysaccharide antibody concentration titer
      and functional activity of the resulting antibodies. METHODS: Fifty-nine
      consecutive patients undergoing splenectomy after trauma were randomized to
      receive pneumococcal vaccine postoperatively at 1, 7, or 14 days. Immunoglobulin
      G serum antibody concentrations against serogroup 4 and serotypes 6B, 19F, and
      23F were measured before vaccination and 4 weeks postvaccination. Antibody
      concentrations were determined by enzyme-linked immunosorbent assay, and
      functional antibody by opsonophagocytosis. Results were compared with a normal
      adult control group (n = 12). RESULTS: Postvaccination enzyme-linked
      immunosorbent assay immunoglobulin G antibody concentrations for all serogroups
      and serotypes studied were not significantly different in splenectomized patients
      and control subjects. Postvaccination functional antibody activity was
      significantly reduced in early vaccination groups (serotype 6B excepted).
      However, with the exception of 19F, all titers for the 14-day group approached
      those of the control subjects (p > 0.05). Fold-increases of opsonophagocytic
      titers for serogroup 4 and serotypes 6B and 19F showed progressive increases with
      delay in vaccination. Except for serotype 23F, the number of postsplenectomy
      patients with opsonophagocytic titers <64 significantly decreased with a delay in
      vaccination (14 days). CONCLUSIONS: Postvaccination immunoglobulin G serum
      antibody concentrations were not significantly different from normal control
      subjects regardless of the time of vaccination (1, 7, or 14 days). Although
      concentrations approach normal, functional antibody activity was significantly
      lower. Better functional antibody responses against the serogroup and serotypes
      studied seemed to occur with delayed (14-day) vaccination.

PMID- 9603076
TI  - Circulating mediators in serum of injured patients with septic complications
      inhibit neutrophil apoptosis through up-regulation of protein-tyrosine
      phosphorylation.
AB  - BACKGROUND: The accumulation of neutrophils at inflammatory sites results in
      excessive release of toxic metabolites causing tissue injury. Proinflammatory
      cytokines may cause the breakdown of homeostasis of neutrophil numbers through
      inhibition of apoptosis. METHODS: Neutrophils were isolated from healthy humans
      and from patients with multiple injuries on day of admission and during septic
      complications. Apoptosis was quantitated using propidium iodide fluorescence and
      the TUNEL method. Tyrosine phosphorylation was measured by flow cytometry.
      RESULTS: Neutrophil apoptosis was decreased (33.3 +/- 5.5%; p < 0.05) in injured
      patients with sepsis compared with healthy humans (87.2 +/- 3.0%) and injured
      patients without sepsis (76.0 +/- 2.0%). Serum from injured patients with sepsis
      inhibited (p < 0.05) apoptosis of neutrophils from healthy humans in a dose
      dependent manner. Serum from healthy humans and from injured patients at
      admission was ineffective. Neutralization of granulocyte-colony stimulating
      factor, but not of granulocyte-macrophage-colony stimulating factor, in serum of
      injured patients with sepsis partially abrogated (+51.2%) serum induced
      prolongation of neutrophil life span. Reduction of neutrophil apoptosis was
      concomitant with increased tyrosine phosphorylation. CONCLUSIONS: Septic
      complications, but not the injury itself, result in inhibition of spontaneous
      neutrophil apoptosis. Circulating mediators seem to reduce neutrophil apoptosis
      through up-regulation of tyrosine phosphorylation.

PMID- 9603077
TI  - Prostaglandin E2 alterations during sepsis are partially mediated by endotoxin
      induced inhibition of prostaglandin 15-hydroxydehydrogenase.
AB  - Prostaglandin E2 (PGE2) is significantly elevated in the plasma of septic or
      injured patients and is thought to be a component of the resultant immune
      suppression associated with augmented rates of infection and mortality. Many
      studies have examined the effect of burn injury and sepsis on PGE2 synthesis.
      However, the effect of sepsis or burn injury on the expression of prostaglandin
      15-hydroxydehydrogenase (PGDH), the key enzyme responsible for PGE2 degradation,
      has not been explored. The aim of this study was to examine the effect of
      endotoxin treatment and/or burn injury on the expression of PGDH. Male BDF1 mice
      were assigned to four groups (n = 4/group): sham, lipopolysaccharide (LPS) (2.5
      mg/kg, Escherichia coli LPS, i.p.), burn (15% body surface area scald injury),
      and burn + LPS (15% body surface area + 2.5 mg/kg LPS, i.p.). Lung tissue was
      harvested at specific time points after treatment and subsequently was processed
      for total RNA and protein. Northern and Western blot analyses were used to
      examine differences in PGDH protein and mRNA expression. Total RNA was probed
      with the riboprobe for murine PGDH, and the 100,000 g protein fraction was
      immunoblotted using an rabbit antimurine PGDH antibody. PGDH was expressed in
      lung at t = 0 in both the saline and LPS-treated animals. A decrease in mRNA
      expression was initially observed at 2 hours after LPS treatment. The decrease
      was also significant (p < 0.05) at 3 hours after LPS and maximal decrease in mRNA
      and protein expression was observed at 6 hours. At 24 hours after LPS
      administration, the PGDH mRNA and protein expression was still significantly
      depressed to 49% of control expression. PGDH expression was similar and not
      statistically different in both burn and burn + LPS treatment at t = 0. At 2
      hours after LPS, PGDH mRNA expression in the burn + LPS treatment group had
      significantly decreased to 47% in comparison with the burn alone group. Maximal
      decrease in PGDH mRNA and protein expression in lung from burn + LPS was observed
      at 6 hours after LPS treatment. This change represents a 73% decrease in mRNA in
      comparison with the time-matched burn control. At 24 hours after LPS
      administration, PGDH mRNA but not protein expression in the lung from burn + LPS
      treated mice was still significantly decreased. In summary, LPS treatment alters
      PGDH mRNA expression at the transcriptional and protein levels. Consequently,
      sepsis-induced increases in PGE2 levels may not be only due to increased PGE2
      synthesis but also due to decreased PGDH expression and, hence, PGE2 degradation.

PMID- 9603078
TI  - Signaling of apoptotic lung injury by lipid hydroperoxides.
AB  - BACKGROUND: Acute lung injury is common after shock and sepsis, but the
      pathophysiology is unclear. Lipid hydroperoxide products including 4
      hydroxynonenal (HNE) increase significantly during these insults and may induce
      apoptosis. This study investigates the role of pathophysiologic concentrations of
      HNE on isolated lung biophysical function and apoptosis. METHODS: Male Sprague
      Dawley rat lungs were isolated and perfused with Krebs-Henseleit buffered
      solution for 120 minutes. Hydroxynonenal (50 micromol/L) or vehicle was added to
      the perfusate at 60 minutes. Lung elastance and perfusion pressure were
      determined. Perfusate glutathione and lactate dehydrogenase were determined at 30
      minute intervals. Genomic DNA was extracted for electrophoretic determination of
      apoptotic laddering. RESULTS: There were no differences in any parameter measured
      before HNE infusion. Lung edema increased significantly with HNE infusion; a
      trend increase in lung elastance and perfusion pressure was noted. DNA laddering
      characteristic of apoptosis was noted in HNE-treated lungs that was absent in
      control animals. CONCLUSION: Lipid hydroperoxide products formed during shock or
      sepsis may be causally related to lung injury. Low concentrations of a candidate
      metabolite, HNE, appear to induce significant lung injury and apoptosis, which
      may partially mediate lung injury during shock and sepsis.

PMID- 9603079
TI  - Endothelial cell injury, as quantified by the soluble thrombomodulin level,
      predicts sepsis/multiple organ dysfunction syndrome after blunt trauma.

PMID- 9603080
TI  - Increased skeletal muscle Na+, K+-ATPase activity as a cause of increased lactate
      production after hemorrhagic shock.
AB  - BACKGROUND: Lactate production after hemorrhagic shock may be produced by aerobic
      glycolysis, which has been linked to activity of the Na+/K+ pump in smooth muscle
      and other tissues. We tested whether increased muscle Na+/K+ pump activity after
      shock was linked to increased lactate production. METHODS: Male Sprague-Dawley
      rats were subjected to 1 or 2 hours of hemorrhagic shock and then resuscitated
      with shed blood and normal saline. After 24 hours, pairs of extensor digitorum
      longus muscles were preincubated for 30 minutes in Krebs buffer (95:5, O2:CO2)
      with 10 mmol/L glucose. One muscle served as a control and was incubated in
      buffer alone; the other was incubated in buffer with 1 mmol/L ouabain, an
      inhibitor of the Na+, K+-ATPase. Lactate, ADP, ATP, glycogen, and creatinine
      phosphate were determined. RESULTS: Under these well-oxygenated conditions,
      muscles from shocked rats produced about twice as much lactate as sham muscles.
      Inhibition of the Na+/K+ pump by ouabain significantly reduced lactate
      production. CONCLUSIONS: Hypoxia is unlikely to account for increased muscle
      lactate production after resuscitated hemorrhagic shock, because high lactate
      production persists under well-oxygenated incubation conditions. Inhibition of
      shock-induced lactate production by ouabain indicates energetic coupling of
      glycolysis to the Na+, K+-ATPase.

PMID- 9603081
TI  - Trauma mortality patterns in three nations at different economic levels:
      implications for global trauma system development.
AB  - BACKGROUND: Whereas organized trauma care systems have decreased trauma mortality
      in the United States, trauma system design has not been well addressed in
      developing nations. We sought to determine areas in greatest need of improvement
      in the trauma systems of developing nations. METHODS: We compared outcome of all
      seriously injured (Injury Severity Score > or = 9 or dead), nontransferred,
      adults managed over 1 year in three cities in nations at different economic
      levels: (1) Kumasi, Ghana: low income, gross national product (GNP) per capita of
      $310, no emergency medical service (EMS); (2) Monterrey, Mexico: middle income,
      GNP $3,900, basic EMS; and (3) Seattle, Washington: high income, GNP $25,000,
      advanced EMS. Each city had one main trauma hospital, from which hospital data
      were obtained. Annual budgets (in US$) per bed for these hospitals were as
      follows: Kumasi, $4,100; Monterrey, $68,000; and Seattle, $606,000. Data on
      prehospital deaths were obtained from vital statistics registries in Monterrey
      and Seattle, and by an epidemiologic survey in Kumasi. RESULTS: Mean age (34
      years) and injury mechanisms (79% blunt) were similar in all locations. Mortality
      declined with increased economic level: Kumasi (63% of all seriously injured
      persons died), Monterrey (55%), and Seattle (35%). This decline was primarily due
      to decreases in prehospital deaths. In Kumasi, 51% of all seriously injured
      persons died in the field; in Monterrey, 40%; and in Seattle, 21%. Mean
      prehospital time declined progressively: Kumasi (102 +/- 126 minutes) > Monterrey
      (73 +/- 38 minutes) > Seattle (31 +/- 10 minutes). Percent of trauma patients
      dying in the emergency room was higher for Monterrey (11%) than for either Kumasi
      (3%) or Seattle (6%). CONCLUSIONS: The majority of deaths occur in the
      prehospital setting, indicating the importance of injury prevention in nations at
      all economic levels. Additional efforts for trauma care improvement in both low
      income and middle-income developing nations should focus on prehospital and
      emergency room care. Improved emergency room care is especially important in
      middle-income nations which have already established a basic EMS.

PMID- 9603082
TI  - The impact of true partnership between a university Level I trauma center and a
      community Level II trauma center on patient transfer practices.
AB  - OBJECTIVE: To examine the effect of a clinical and administrative partnership
      with an academic urban Level I trauma center on the patient transfer practices at
      a suburban/rural Level II center. METHODS: Data for 2 years before affiliation
      (PRE) abstracted from inpatient charts and the trauma registry were compared with
      that for 2 years after (POST). The following data were collected: number of,
      reason for, and destination and demographics of transfers. Chi(2) test and t test
      analyses were used; p < 0.05 defined significance; data are mean +/- SEM.
      RESULTS: Transfer rate increased from 4% PRE to 6.9% (p = 0.001) POST with no
      significant difference in age, Glasgow Coma Scale score, Injury Severity Score,
      or Revised Trauma Score. Repatriation occurred in 12.8% POST (none PRE). The
      current Level I facility accepted 1.8% of all transfers PRE and 36.4% POST (p =
      0.0001). PRE/POST rates by reason are as follows: pediatric, 14.6%/9.0% (p =
      0.04); intensive care unit, 0.4%/1.7% (p = 0.13); complex orthopedic, 100%/0% (p
      = 0.005); vascular, 50%/0% (p = 0.008); spinal cord injury, 100%/100%; and
      ophthalmologic, 0%/100% (p = 0.005). CONCLUSIONS: In this experience of Level
      I/II partnership (1) transfer patterns were altered, (2) select patient cohort
      transfers decreased (pediatric, complex orthopedic, vascular), whereas others
      increased (aortic work-up), and (3) repatriation rates were low.

PMID- 9603083
TI  - Change in morbidity patterns after adoption of the American College of Surgeons
      complication coding system in a regional trauma center: results of a prospective
      study.

PMID- 9603084
TI  - Relationship of trauma patient volume to outcome experience: can a relationship
      be defined?
AB  - OBJECTIVES: Five years experience recorded in a multi-institutional pediatric
      trauma registry was analyzed to define the relationship between case volume and
      outcome as measured by mortality. METHODS: A total of 30,930 records with
      complete data were categorized by contributing hospital. Patients with fatal
      injury as indicated by an injury severity score of 75 or any abbreviated injury
      scale of 6 were excluded. Each center's experience was stratified by injury
      severity using injury severity score > or = 15 as indicative of severe injury.
      Centers were then classified as low volume (LV, 100-500 cases), mid volume (MV,
      501-1,000 cases), or high volume (HV, > 1,000 cases). Proportion of patients with
      severe injury (injury severity score > 15) and mortality were compared among
      groups using the chi(2) test with significance accepted at p < 0.05. Using the
      Pediatric Risk Indicator to adjust for mortality risk, the combined hospital
      experience of each volume group was further analyzed to assess performance with
      specific levels of increasing injury severity. RESULTS: Findings demonstrated a
      trend of increasing mortality with increasing volume, despite a consistent
      proportion of severe injury. Risk adjusted mortality for each volume class
      indicates best outcome in the mid level group. CONCLUSIONS: Regardless of overall
      volume of patients encountered, there is a consistent proportion of severe
      injury. The increasing mortality with the most severe injuries seen in the high
      volume centers may reflect overdemand on resources.

PMID- 9603085
TI  - Dedicated operating room for trauma: a costly recommendation.
AB  - BACKGROUND: A dedicated operating room (OR) for urgent trauma cases is suggested
      by the American College of Surgeons Committee on Trauma as a necessary component
      of a Level I or II trauma center. We describe a cost analysis of this
      recommendation. METHODS: Two models for staffing urgent trauma cases were
      constructed. Urgent trauma cases were defined as those taken to the OR within 30
      minutes of arrival. In one model the OR was available 24 hours a day with in
      hospital personnel. The second model used an out-of-hospital call schedule,
      assuming a patient-ready OR in 30 minutes. Costs and revenue per urgent case were
      calculated. A break-even analysis shows the number of cases required for costs to
      equal revenue. RESULTS: In the 24-hour model, the cost/urgent case is $14,288; in
      the call-schedule model $3,243. The number of cases to break even in the 24-hour
      model is 1210; in the call-schedule model 375. CONCLUSIONS: A call-schedule model
      is the least costly way to staff an OR for urgent trauma cases.

PMID- 9603086
TI  - The conundrum of the Glasgow Coma Scale in intubated patients: a linear
      regression prediction of the Glasgow verbal score from the Glasgow eye and motor
      scores.
AB  - BACKGROUND: The Glasgow Coma Scale (GCS), which is the foundation of the Trauma
      Score, Trauma and Injury Severity Score, and the Acute Physiology and Chronic
      Health Evaluation scoring systems, requires a verbal response. In some series, up
      to 50% of injured patients must be excluded from analysis because of lack of a
      verbal component for the GCS. The present study extends previous work evaluating
      derivation of the verbal score from the eye and motor components of the GCS.
      METHODS: Data were obtained from a state trauma registry for 24,565 unintubated
      patients. The eye and motor scores were used in a previously published regression
      model to predict the verbal score: Derived Verbal Score = -0.3756 + Motor Score *
      (0.5713) + Eye Score * (0.4233). The correlation of the actual and derived verbal
      and GCS scales were assessed. In addition the ability of the actual and derived
      GCS to predict patient survival in a logistic regression model were analyzed
      using the PC SAS system for statistical analysis. The predictive power of the
      actual and the predicted GCS were compared using the area under the receiver
      operator characteristic curve and Hosmer-Lemeshow goodness-of-fit testing.
      RESULTS: A total of 24,085 patients were available for analysis. The mean actual
      verbal score was 4.4 +/- 1.3 versus a predicted verbal score of 4.3 +/- 1.2 (r =
      0.90, p = 0.0001). The actual GCS was 13.6 + 3.5 versus a predicted GCS of 13.7
      +/- 3.4 (r = 0.97, p = 0.0001). The results of the comparison of the prediction
      of survival in patients based on the actual GCS and the derived GCS show that the
      mean actual GCS was 13.5 + 3.5 versus 13.7 + 3.4 in the regression predicted
      model. The area under the receiver operator characteristic curve for predicting
      survival of the two values was similar at 0.868 for the actual GCS compared with
      0.850 for the predicted GCS. CONCLUSIONS: The previously derived method of
      calculating the verbal score from the eye and motor scores is an excellent
      predictor of the actual verbal score. Furthermore, the derived GCS performed
      better than the actual GCS by several measures. The present study confirms
      previous work that a very accurate GCS can be derived in the absence of the
      verbal component.

PMID- 9603087
TI  - Hypothermic coagulopathy in trauma: effect of varying levels of hypothermia on
      enzyme speed, platelet function, and fibrinolytic activity.
AB  - BACKGROUND: The coagulopathy noted in hypothermic trauma patients has been
      variously theorized to be caused by either enzyme inhibition, platelet
      alteration, or fibrinolytic processes, but no study has examined the possibility
      that all three processes may simultaneously contribute to coagulopathy, but are
      perhaps triggered at different levels of hypothermia. The purpose of this study
      was to determine whether, at clinically common levels of hypothermia (33.0-36.9
      degrees C), there are specific temperature levels at which coagulopathic
      alterations are seen in each of these processes. METHODS: Of 232 consecutive
      adult trauma patients presenting to a Level I trauma center, 112 patients met the
      inclusion criteria of an Injury Severity Score of 9 or greater and time since
      injury of less than 2 hours. Of the included patients, 40 were normothermic and
      72 were hypothermic (> or =37 degrees C, n = 40; 36.9-36 degrees C, n = 29; 35.9
      35 degrees C, n = 20; 34.9-34 degrees C, n = 16; 33.9-33 degrees C, n = 7).
      Included patients were prospectively studied with thrombelastography adjusted to
      core body temperature. Additionally, PT, aPTT, platelets, CO2, hemoglobin,
      hematocrit, and Injury Severity Score were measured. RESULTS: Analysis by
      multivariate analysis of variance of the relationship between coagulation and
      temperature demonstrated that in hypothermic trauma patients, 34 degrees C was
      the critical point at which enzyme activity slowed significantly (p < 0.0001),
      and at which significant alteration in platelet activity was seen (p < 0.001).
      Fibrinolysis was not significantly affected at any of the measured temperatures
      (p > 0.25). CONCLUSIONS: Patients whose temperature was > or =34.0 degrees C
      actually demonstrated a significant hypercoagulability. Enzyme activity slowing
      and decreased platelet function individually contributed to hypothermic
      coagulopathy in patients with core temperatures below 34.0 degrees C. All the
      coagulation measures affected are part of the polymerization process of platelets
      and fibrin, and this process may be the mechanism by which the alteration in
      coagulation occurs.

PMID- 9603088
TI  - Reuse of external skeletal fixator components: effects on costs and
      complications.
AB  - BACKGROUND: Although many community hospitals and trauma centers reuse external
      fixator components, no published studies have examined the cost-effectiveness or
      the effect on the rate of complications of reuse. This study reports the
      preliminary results of a program for the reuse of selected components of external
      fixators at a trauma center. METHODS: After removal from the patient, fixators
      were cleaned and examined by a single nurse responsible for the program.
      Components in good repair were returned to the operating room stock for reuse,
      whereas those showing specific signs of wear were discarded. No component was
      used more than three times. The medical center charged patients a loaner fee
      equal to the hospital's cost for reusable components of external fixators. Data
      were collected for all fixators applied in the 15 months before and after
      institution of the program (69 and 65 fixators, respectively). RESULTS: The
      overall mean hospital charge for a fixator decreased 32% as a result of the reuse
      program (from $4,067 to $2,791). For the two fractures most commonly treated with
      external fixation, the distal radius and tibial plafond fractures, the mean
      charge decreased 44 and 29%, respectively. The mean hospital cost for a fixator
      decreased 34% as a result of the program (from $1,864 to $1,238). There were no
      differences in the rates of reoperation or complications before and after
      institution of the reuse program. No patient had mechanical failure of a new or
      reused fixator body. CONCLUSION: The preliminary results of this program are
      encouraging. We recommend that institutions reusing these devices develop
      specific programs outlining criteria for reuse and guidelines for reprocessing
      devices for reuse. The results of this study represent an important first step in
      the validation of the efficacy and safety of reuse of external fixator
      components.

PMID- 9603089
TI  - Treatment of humeral shaft fractures with humeral locked nail and comparison with
      plate fixation.
AB  - OBJECTIVE: To report the experience of a newly devised humeral locked nail in
      treating acute humeral shaft fractures and to compare its effectiveness with that
      of plate fixation. DESIGN AND METHODS: Data were collected on 48 acute humeral
      shaft fractures in 48 consecutive patients treated with humeral locked nails and
      compared with retrospective data on 25 fractures in 25 other patients treated
      with dynamic compression plates. The operation time, amount of blood transfusion,
      time to union, complications, and functional recovery were recorded and compared.
      The average follow-up time was 20.5 months for the nail group and 33.3 months for
      the plate group. Student's t test and Fisher's Exact Test were used for
      statistical analyses. RESULTS: Locked nailing had significantly shorter operation
      time and less blood transfusion than did plate fixation, 68 versus 93 minutes and
      0 versus 102 mL, respectively. Eventual union was achieved among all in the nail
      group and among all but one in the plate group. Union rate and time to union were
      not significantly different. In the plate group, three fractures had
      complications: one with implant loosening and nonunion, one with deep infection,
      and one with postoperative radial nerve palsy; the nail group had no
      complications. The difference in complication rates was statistically
      significant. In the nail group, one varus malunion and one intraoperative
      comminution occurred, without adverse consequences. Functional recovery was
      essentially the same in both groups for uncomplicated fractures. CONCLUSIONS:
      Humeral locked nailing offered a less invasive surgical technique and more
      favorable treatment results than did plate fixation. Correct nailing direction,
      precise surgical techniques, less bulky hardware, and stable transfixing screws
      are the keys to a successful treatment. Further prospective, randomized
      comparative study is warranted.

PMID- 9603090
TI  - Patients with gunshot wounds to the head do not require cervical spine
      immobilization and evaluation.
AB  - OBJECTIVE: The purpose of this study was to determine the incidence of indirect
      spinal column injury in patients sustaining gunshot wounds to the head. METHODS:
      A retrospective review of patient records and autopsy reports was conducted of
      patients admitted with gunshot wounds to the head between July of 1990 and
      September of 1995 were included. Those with gunshot wounds to the neck and those
      who were dead on arrival were excluded. RESULTS: A total of 215 patients were
      included in the study. Cervical spine clearance in 202 patients (93%) was
      determined either clinically, radiographically, or by review of postmortem
      results. No patients sustained indirect (blast or fall-related) spinal column
      injury. Three patients had direct spinal injury from bullet passage that were
      apparent from bullet trajectory. More intubation attempts occurred in patients
      with cervical spine immobilization (49 attempts in 34 patients with
      immobilization versus five attempts in four patients without cervical spine
      immobilization, p = 0.008). CONCLUSIONS: Indirect spinal injury does not occur in
      patients with gunshot wounds to the head. Airway management was compromised by
      cervical spine immobilization. Protocols mandating cervical spine immobilization
      after a gunshot wound to the head are unnecessary and may complicate airway
      management.

PMID- 9603091
TI  - Importance of a reliable admission Glasgow Coma Scale score for determining the
      need for evacuation of posttraumatic subdural hematomas: a prospective study of
      65 patients.
AB  - BACKGROUND: Patients who have an acute subdural hematoma with a thickness of 10
      mm or less and with a shift of the midline structures of 5 mm or less often can
      be treated nonoperatively. We wonder whether the knowledge of the clinical status
      both in the prehospital determination and on admission to the neurosurgical
      center can predict the need for evacuation of subdural hematomas as well as the
      computed tomographic (CT) parameters. METHODS: From January 1, 1994, to May 31,
      1996, 65 comatose patients harboring an acute subdural hematoma of 5 mm or more
      and not brain dead were admitted to our intensive care unit. Of the 65 patients,
      15 patients were initially managed conservatively according to a protocol based
      on clinical, CT, and intracranial pressure parameters. During the study period,
      the use of long-lasting paralytic agents has been eliminated to allow detection
      of clinical deterioration in the Glasgow Coma Scale (GCS) score from the
      prehospital determination to the hospital admission assessment. RESULTS: Of the
      15 patients initially managed conservatively, two were subsequently operated on
      because of evolving parenchymal hematomas. When comparing demographic, clinical,
      and CT parameters between the surgical group of patients and the patients
      initially conservatively treated, hematoma thickness (mean, 17.1 mm vs. 7.5 mm, p
      < 0.0001) and shift of the midline structures (mean, 12.8 mm vs. 4.7 mm, p <
      0.008) were predictive of the need for surgery. A statistically significant
      change in the GCS score between prehospital determination and admission
      assessment was shown in the surgical group of patients (mean GCS score, 8.4 vs.
      6.7, p < 0.01), and it was not present (mean GCS score, 7.3 vs. 7.2) in the
      patients initially conservatively treated. Functional outcomes were present in 23
      cases (35.4%); functional outcomes in the initially conservatively treated
      patients were reached by 10 patients (66.7%). CONCLUSIONS: Nonoperative
      management for selected cases of acute subdural hematomas is at least as safe as
      surgical management. GCS scoring at the scene and in the emergency room combined
      with early and subsequent CT scanning is crucial when making the decision for
      nonoperative management. This strategy requires that administration of long
      lasting sedatives and paralytic medications be avoided before the patient arrives
      at the neurosurgical center.

PMID- 9603092
TI  - Cytokines and adhesion molecules in elective and accidental trauma-related
      ischemia/reperfusion.
AB  - BACKGROUND: The major pathophysiologic role of cytokines such as tumor necrosis
      factor (TNF)-alpha, interleukin (IL)-1, and IL-6, as well as of the (soluble)
      adhesion molecules ICAM-1 and E-selectin, has been identified using different
      experimental models of ischemia/reperfusion injury. Moreover, in intensive care
      management, evaluation of these agents as diagnostic or prognostic tools is of
      great interest in ischemia/reperfusion injury caused by surgical or accidental
      trauma. For this reason, inflammatory mediators including those mentioned above
      were investigated in three different groups of surgical patients. METHODS: The
      first group (A, n = 13) comprised patients undergoing elective limb surgery
      without a tourniquet. The second group (B, n = 36) included patients subjected to
      limb surgery with a tourniquet. The third group (C, n = 30) was composed of
      accidental trauma patients who were retrospectively divided into those with and
      without multiple organ dysfunction (+MOD and -MOD, respectively) as defined by
      the Denver Score. Serial blood samples were taken during a 5-day (elective
      surgery) or 14-day (accidental trauma) observation period for monitoring of
      cytokines and soluble adhesion molecules. The clinical course and the degree of
      MOD were recorded daily. RESULTS: Only when a tourniquet was applied for a mean
      time of 105 minutes did elective limb surgery result in significantly increased
      serum levels of IL-6, IL,-1ra, and IL-10 but not TNF-RII. Yet, the increase in
      cytokine levels was not sufficient to cause an enhanced shedding of adhesion
      molecules, and both soluble ICAM-1 and soluble E-selectin remained unchanged in
      groups A and B throughout the 5-day observation period. In patients with multiple
      injuries (group C), all parameters increased early after trauma up to 10- to 20
      fold in comparison with the elective limb surgery patients in groups A and B.
      When the accidental trauma patients were divided according to the Denver Score
      for +MOD (n = 8, mean Injury Severity Score = 33.8) and -MOD (n = 22, mean Injury
      Severity Score = 31.2), a clear difference became evident in serum IL-6 and IL
      1ra levels within the first 4 days and in serum IL-10 levels for the first 2 days
      after trauma, with cytokine levels being significantly higher in the +MOD
      patients 3 to 4 days before the onset of MOD. Although highly elevated, TNF-RII
      levels did not differentiate between +MOD and -MOD at any time. The increase in
      serum cytokine levels was associated with a remarkable expression and shedding of
      ICAM-1 and E-selectin made obvious by significantly increased soluble serum ICAM
      1 levels in +MOD patients compared with the -MOD group between days 3 and 5 after
      trauma and increased soluble serum E-selectin levels between days 2 and 4 after
      trauma. CONCLUSION: The release of cytokines and soluble adhesion molecules into
      the circulation correlates well with the degree of trauma (elective surgery vs.
      accidental multiple trauma), depending on the extent of the associated
      ischemia/reperfusion injury. Both groups of mediators are also clearly related to
      the development of MOD in patients with multiple injuries with generalized
      ischemia/reperfusion injury caused by hemorrhagic shock. They may be predictive
      of patients at risk for MOD when measured early in the posttraumatic period.

PMID- 9603093
TI  - Percutaneous diagnostic peritoneal lavage using a Veress needle versus an open
      technique: a prospective randomized trial.
AB  - OBJECTIVE: To prospectively compare the speed, sensitivity, complications, and
      technical failures of percutaneous diagnostic peritoneal lavage (DPL) using a
      Veress needle versus open DPL. METHODS: One hundred seventy-six blunt trauma
      patients requiring DPL were prospectively randomized to undergo either open DPL
      using a standard technique or percutaneous DPL using an 18-gauge Veress needle to
      penetrate the peritoneal cavity, with the lavage catheter then being inserted
      over a guide wire. RESULTS: Mean time to successful placement of the lavage
      catheter for the percutaneous Veress needle technique was 2.73 minutes versus
      7.28 minutes for the open DPL technique (p < 0.001). Sixteen percent of open
      lavage procedures took more than 11 minutes; the majority (60%) of Veress needle
      lavage procedures took less than 2 minutes. There were no false-negative findings
      in either group, and there was one false-positive result in each group. A wound
      infection after an open DPL was the only complication. Poor return of lavage
      fluid (<200 mL) accounted for most technical failures; this was more prevalent
      with the percutaneous method (11.2%) than with the open technique (3.8%) (p <
      0.05). CONCLUSION: The percutaneous DPL method using a Veress needle is
      significantly faster than the open DPL method. The Veress needle lavage was as
      safe and as sensitive as the open lavage; however, technical failure occurred
      more frequently with the Veress needle lavage than with the open DPL.

PMID- 9603094
TI  - Incidence and significance of free fluid on abdominal computed tomographic scan
      in blunt trauma.
AB  - OBJECTIVE: To determine the incidence and significance of free fluid on abdominal
      CT in blunt trauma. DESIGN: Retrospective chart review. METHODS: All blunt trauma
      patients with an abdominal computed tomographic scan from August of 1993 to
      December of 1995 were identified from the trauma registry at a Level 1 trauma
      center. A total of 1,159 computed tomographic scans were performed; records of 18
      patients were excluded for incomplete records. Official reports of computed
      tomographic scans were reviewed for free fluid, solid organ injury, bladder
      injury, and pelvic fracture. RESULTS: Free fluid without solid organ injury was
      found in 3% (34 of 1141). Laparotomy was performed because of free fluid in 13
      patients. There were six small bowel injuries and one diaphragm injury for a
      therapeutic laparotomy rate of 54%. Ten patients had trace free fluid and did not
      undergo laparotomy; none had a missed small bowel injury. CONCLUSIONS: The
      presence of more than trace amounts of free fluid without solid organ injury in
      patients with blunt trauma is a strong indication for exploratory laparotomy.
      Patients with isolated trace amounts of free fluid can be safely observed.

PMID- 9603095
TI  - Computed tomography in the initial evaluation of hemodynamically stable patients
      with blunt abdominal trauma: impact of severity of injury scale and technical
      factors on efficacy.
AB  - BACKGROUND: Although computed tomography is used widely in evaluating injuries
      from blunt abdominal trauma, grading of injuries does not reliably predict the
      need for intervention. Objective reporting is essential to evaluate accuracy and
      facilitate patient triage. We established and tested a five-point grading system
      for overall severity of injury. METHODS: A total of 392 computed tomographic
      trauma cases were objectively classified according to the type and severity of
      abdominal injuries, by two experienced radiologists. Interobserver variability
      between the original interpretation and the consensus of the film reviewers was
      evaluated. The computed tomographic grading system was measured against rate of
      admission, exploratory laparotomy, and further imaging. RESULTS: Patients with
      higher grades of injury on computed tomography were increasingly likely to have
      surgical management (odds ratio, 3.99; 95% confidence interval, 1.86-8.58; p <
      0.0006), with sensitivity 100%, specificity 89.5% for level 2 injuries and
      higher. Although there was almost perfect agreement between the official
      interpretation and the reviewers' blinded consensus interpretation (raw agreement
      84%, weighted kappa 0.86), indeterminate studies were reduced from 23% (16 of 67)
      to 12% (8 of 67) on review: these were more likely to have metallic or motion
      artifacts (5 of 16 vs. 1 of 51 p < 0.002). CONCLUSIONS: Standardizing reporting
      of injuries enhances accuracy, and grading eliminates equivocation. Diagnostic
      certainty in computed tomography of blunt abdominal trauma is reduced by motion
      and metallic artifacts.

PMID- 9603096
TI  - Diagnostic validity of pulmonary artery catheterization for residents at an
      intensive care unit.
AB  - OBJECTIVE: To assess the amount of additional information provided by
      measurements derived from pulmonary artery catheter (PAC) use beyond that derived
      from clinical evaluation by intensive care residents. METHODS: One hundred forty
      nine consecutive patients undergoing right-heart catheterization were
      prospectively included in the study. Before inserting a PAC, physicians had to
      predict pulmonary arterial pressure (PAP), pulmonary capillary wedge pressure
      (PCWP), systemic vascular resistance index (SVRI), cardiac index (CI), mixed
      venous oxygen saturation (SvO2), oxygen delivery (DO2), oxygen consumption (VO2),
      and pulmonary shunt fraction (Qs/Qt) by selecting a given option on a
      questionnaire. Ranges of options were chosen to create clear clinical differences
      among them. RESULTS: The correct value was predicted in a median of 50% of cases
      (range, 45-63%). PAP was predicted correctly in 55%, PCWP in 46%, SVRI in 63%, CI
      in 62%, SvO2 in 45%, DO2 in 45%, VO2 in 51%, and Qs/Qt in 51%. A significant
      difference was found between estimated and measured values for all parameters (p
      < 0.01). No significant differences were detected between more and less
      experienced physicians. There was no significant difference between estimated and
      measured values with respect to the different courses of intensive care unit
      admissions or the different indications for PAC insertion. CONCLUSION: In a
      selected group of critically ill patients, the PAC adds valuable and clinically
      relevant information to clinical assessment in about 50% of cases. Its use should
      not be withheld in patients with unclear hemodynamic and metabolic profiles.

PMID- 9603097
TI  - Recipe for poor man's fibrin glue.

PMID- 9603098
TI  - In search of the optimal end points of resuscitation in trauma patients: a
      review.
AB  - Complete resuscitation from shock is one of the primary concerns of the surgeon
      taking care of injured patients. Traditionally, the return to normalcy of blood
      pressure, heart rate, and urine output has been the end point of resuscitation.
      Using these end points may leave a substantial number of patients, up to 50 to
      85% in some series, in "compensated" shock, which if it persists may ultimately
      lead to the death of the patient. Because of this potential other end points are
      being used and include supernormal values for oxygen transport variables (cardiac
      index, oxygen delivery, and oxygen consumption), lactate, base deficit, and
      gastric intramucosal pH. We believe that the current data support the use of
      lactate, base deficit, and/or gastric intramucosal pH as the appropriate end
      points of resuscitation of trauma patients. The goal should be to correct one or
      all of three of these markers of tissue perfusion to normal within the initial 24
      hours after injury.

PMID- 9603099
TI  - Tension pneumoperitoneum after blast injury: dramatic improvement in ventilatory
      and hemodynamic parameters after surgical decompression.
AB  - Tension pneumoperitoneum is a known although rare complication of barotrauma,
      which can accompany blast injury. We report two patients who suffered from severe
      pulmonary blast injury, accompanied by tension pneumoperitoneum, and who were
      severely hypoxemic, hypercarbic, and in shock. After surgical decompression of
      their pneumoperitoneum, respiratory and hemodynamic functions improved
      dramatically. Several mechanisms to explain this improvement are suggested. In
      such cases the release of the tension pneumoperitoneum is mandatory, and
      laparotomy with delayed closure can be contemplated.

PMID- 9603100
TI  - Successful emergency right pneumonectomy for deep laceration of the lung: case
      report.

PMID- 9603101
TI  - Pulmonary torsion of the right upper lobe after right middle lobectomy for a stab
      wound to the chest.

PMID- 9603102
TI  - Anterior ischemic optic neuropathy after hemorrhagic shock.

PMID- 9603103
TI  - Facial trauma from a snapped-back water ski towbar.

PMID- 9603104
TI  - Communicating bone cyst of the posterior fossa after craniocerebral erosion
      (growing fracture of the skull): case report.

PMID- 9603105
TI  - Gastric rupture and tension pneumoperitoneum complicating cardiopulmonary
      resuscitation: case report.

PMID- 9603106
TI  - Subtotal splenectomy for treatment of severe splenic injuries.
AB  - OBJECTIVE: The spleen is an organ of the defense system with important roles in
      filtering functions, phagocytosis, and immunoglobulin production. Septic
      phenomena are severe complications that may occur after total splenectomy. To
      avoid these adverse effects, the preservation of the spleen is indicated.
      However, in the presence of severe spleen damage, lesions of the splenic pedicle,
      or both, complete removal of the spleen has been considered unavoidable. METHODS:
      The present paper presents the preservation of the upper splenic pole supplied by
      the splenogastric vessels in six patients with severe injuries of the spleen and
      its pedicle. RESULTS: All patients had good postoperative courses. CONCLUSIONS:
      Subtotal splenectomy may be useful in the treatment of severe injuries of the
      distal part of the spleen, when the vessels of its pedicle are damaged, or both.

PMID- 9603107
TI  - We feel our system has been convicted without trial and respectfully ask, as
      stated in our article, that it be validated by an independent body of
      researchers.

PMID- 9603108
TI  - Posttraumatic right coronary artery aneurysm complicated with acute myocardial
      infarction shortly after blunt chest trauma.

PMID- 9603109
TI  - Is nitric oxide inhalation a "cosmetic" therapy in acute respiratory distress
      syndrome?

PMID- 9603110
TI  - The role of leukotriene modifiers in the treatment of asthma.

PMID- 9603111
TI  - Inhaled nitric oxide versus conventional therapy: effect on oxygenation in ARDS.
AB  - A randomized, controlled clinical trial was performed with patients with acute
      respiratory distress syndrome (ARDS) to compare the effect of conventional
      therapy or inhaled nitric oxide (iNO) on oxygenation. Patients were randomized to
      either conventional therapy or conventional therapy plus iNO for 72 h. We tested
      the following hypotheses: (1) that iNO would improve oxygenation during the 72 h
      after randomization, as compared with conventional therapy; and (2) that iNO
      would increase the likelihood that patients would improve to the extent that the
      FI(O2) could be decreased by > or = 0.15 within 72 h after randomization. There
      were two major findings. First, That iNO as compared with conventional therapy
      increased Pa(O2)/FI(O2) at 1 h, 12 h, and possibly 24 h. Beyond 24 h, the two
      groups had an equivalent improvement in Pa(O2)/FI(O2). Second, that patients
      treated with iNO therapy were no more likely to improve so that they could be
      managed with a persistent decrease in FI(O2) > or = 0.15 during the 72 h
      following randomization (11 of 20 patients with iNO versus 9 of 20 patients with
      conventional therapy, p = 0.55). In patients with severe ARDS, our results
      indicate that iNO does not lead to a sustained improvement in oxygenation as
      compared with conventional therapy.

PMID- 9603112
TI  - Effect of zafirlukast (Accolate) on cellular mediators of inflammation:
      bronchoalveolar lavage fluid findings after segmental antigen challenge.
AB  - The effect of zafirlukast (Z) to alter the inflammatory response to segmental
      antigen challenge (SAC) was assessed by bronchoalveolar lavage (BAL) in this
      double-blind, placebo-controlled, two-period, crossover trial in 11 allergic
      asthmatic patients. Patients with asthma and positive skin tests to antigen
      received 7 d of treatment with Z (20 mg twice daily) or placebo (P) during two
      trial periods 14 to 21 d apart. At steady state (Day 5), patients underwent SAC
      followed by BAL immediately after challenge and 48 h later. Purified alveolar
      macrophages were analyzed ex vivo for phorbol myristate acetate (PMA)-driven
      superoxide release. Results were analyzed by analysis of variance (ANOVA). Forty
      eight hours after SAC, Z therapy was associated with significantly reduced BAL
      lymphocytes and alcian blue-positive cells (presumably basophils) compared with P
      (p < 0.01), with a trend toward reduced numbers of alveolar macrophages (p =
      0.06). PMA-driven superoxide release by purified alveolar macrophages was
      significantly reduced 48 h after SAC in the Z versus P arms (p < 0.05). Reduction
      of basophil influx, mediator release, and cellular activation may be important in
      attenuating the late phase of asthma. Collectively, the data suggest that
      zafirlukast therapy alters cellular infiltration and activation associated with
      antigen challenge.

PMID- 9603113
TI  - Bronchial responsiveness and five-year FEV1 decline: a study in miners and
      nonminers.
AB  - Increased nonspecific bronchial responsiveness (NSBR) may be a risk factor for
      the development of chronic airflow obstruction. We evaluated this hypothesis in a
      cohort of 378 underground coal miners and working nonminers. Methacholine testing
      was performed at the beginning and end of a 5-yr study period. Spirometry was
      repeated at 6-mo intervals and individual 5-yr FEV1 slopes were calculated by
      linear regression. Relationships between FEV1 slopes and NSBR were examined using
      multiple linear regression models, controlling for FEV1 level, smoking, and
      mining. Increasing NSBR at the initial survey was associated with a somewhat
      greater rate of subsequent FEV1 decline. Methacholine responders at the final
      survey had a considerably increased rate of decline during the previous years.
      Responsiveness status changed over the 5 yr in 22% of the subjects. Both the
      development and persistence of increased NSBR were strongly associated with
      higher rates of FEV1 decline. In contrast, FEV1 declines were not accelerated
      among workers with increased NSBR that reverted to normal. Smoking and mining
      were both independently associated with FEV1 declines, but did not substantially
      modify the effect of NSBR. Due to its variability over time, NSBR testing
      predicts lung function decline only in some individuals, and its value as a
      prognostic test for chronic airway disorders is limited. Because improvement in
      bronchial hyperresponsiveness was associated with a reduction in the rate of FEV1
      loss, interventions directed at preventing or reducing nonspecific airway
      hyperresponsiveness should be investigated.

PMID- 9603114
TI  - Effects of L-NMMA and fluid loading on TNF-induced cardiovascular dysfunction in
      dogs.
AB  - We investigated the effects of N(omega)-monomethyl-L-arginine (L-NMMA) and fluid
      loading on tumor necrosis factor (TNF)-induced cardiovascular dysfunction in
      awake dogs. L-NMMA (40 mg x kg(-1) given intravenously over a period of 10 min,
      and followed by dosing at 40 mg x kg(-1) x h(-1) for 6 h) and TNF (20 or 45
      microg x kg(-1) given intravenously for 20 min), given alone or in combination,
      significantly decreased stroke volume, cardiac index, oxygen delivery, and left
      ventricular (LV) function plots over a period of 6 h. Of note was that the
      cardiac-depressant effects of TNF and L-NMMA given together were significantly
      less than additive. Thus, the combination was beneficial (or significantly less
      harmful to cardiac performance than expected), possibly because L-NMMA augmented
      cardiac preload as shown by significant increases in both pulmonary capillary
      wedge pressure (PCWP) and central venous pressure (CVP). Fluid challenges at 6 h
      (Ringer's solution at 80 ml x kg(-1) given over a period of 30 min) also
      significantly increased PCWP and CVP, and abolished the beneficial preload effect
      of L-NMMA on cardiac performance. Thus, after fluid loading, the cardiac
      depressant effects of TNF and L-NMMA given together became equal to the sum of
      those produced by TNF and L-NMMA given separately. Although L-NMMA significantly
      decreased serum nitrite/nitrate levels, TNF did not increase these end products
      of nitric oxide (NO) production relative to controls. Therefore, after preload
      abnormalities were eliminated with fluid loading, L-NMMA had no beneficial effect
      on TNF-induced cardiac depression, and TNF did not increase end products of NO
      production. These findings are not consistent with NO being the mechanism of TNF
      induced acute cardiac depression.

PMID- 9603115
TI  - Reduced gas transfer at rest and during exercise in school-age survivors of
      bronchopulmonary dysplasia.
AB  - School-age children who survive bronchopulmonary dysplasia (BPD) may have a
      permanent reduction in alveolar surface area that could limit gas transfer both
      at rest and during exercise. To test this hypothesis, 10 survivors of BPD, 10
      children born prematurely without BPD, and 10 healthy children born at term, 6 to
      9 yr of age, underwent treadmill exercise studies. During a three-phase protocol
      we measured intrabreath acetylene (C2H2) and carbon monoxide (CO) transfer,
      pulmonary function, and SaO2. Both at rest and during exercise, C2H2 transfer
      corrected for body surface area was lower in survivors of BPD than it was in
      children born prematurely without BPD or children born at term. With exercise the
      transfer of both gases increased sharply over resting values in children born
      prematurely and at term. In survivors of BPD C2H2 transfer with exercise did
      increase, but not as much as it did in control subjects, and corrected CO
      transfer did not change at all. In survivors of BPD and children born
      prematurely, FEV1 fell during recovery from exercise, but this did not correlate
      with C2H2 transfer or DL(CO)/VA. Thus, soluble gas transfer at rest and during
      acute exercise is reduced in children who survive BPD. This is likely explained
      either by long-term derangements in lung structure or residual right ventricular
      dysfunction affecting cardiac output.

PMID- 9603116
TI  - Cytochrome oxidase activity and mitochondrial gene expression in skeletal muscle
      of patients with chronic obstructive pulmonary disease.
AB  - Several recent studies have suggested that skeletal muscle bioenergetics are
      abnormal in patients with chronic obstructive pulmonary disease (COPD). This
      study investigates the activity of cytochrome oxidase (COX), the terminal enzyme
      in the mitochondrial electron transport chain, and the expression of two
      mitochondrial DNA genes related to COX (mRNA of subunit I of COX [COX-I] and the
      RNA component of the 12S ribosomal subunit [12S rRNA]), in quadriceps femoris
      muscle biopsies obtained from COPD patients with various degrees of arterial
      hypoxemia, and from healthy sedentary control subjects of similar age. The
      activity of COX was measured spectrophotometrically in fresh tissue at 37 degrees
      C with excess substrate. RNA transcripts were measured using reverse
      transcription and polymerase chain reaction. The measurements of mRNA COX-I and
      12S rRNA were normalized to the mRNA of actin, which is a housekeeping gene not
      influenced by hypoxia. We found that, compared with control subjects, COPD
      patients with chronic respiratory failure (PaO2 < 60 mm Hg) showed increased COX
      activity (p < 0.05). Further, the activity of COX was inversely related to
      arterial PO2 value (Rho -0.59, p < 0.01). The COX-I mRNA content was not
      different between patients and control subjects but patients with chronic
      respiratory failure had higher levels of 12S rRNA (p < 0.05), which were again
      inversely related to PaO2 (Rho -0.49, p < 0.05). These results indicate that the
      activity of COX is increased in skeletal muscle of patients with COPD and chronic
      respiratory failure, and they suggest that this is likely regulated at the
      translational level by increasing the number of mitochondrial ribosomes.

PMID- 9603117
TI  - Effect of exacerbation on quality of life in patients with chronic obstructive
      pulmonary disease.
AB  - Exacerbations occur commonly in patients with moderate or severe chronic
      obstructive pulmonary disease (COPD) but factors affecting their severity and
      frequency or effects on quality of life are unknown. We measured daily peak
      expiratory flow rate (PEFR) and daily respiratory symptoms for 1 yr in 70 COPD
      patients (52 male, 18 female, mean age [+/- SD] 67.5 +/- 8.3 yr, FEV1 1.06 +/-
      0.45 L, FVC 2.48 +/- 0.82 L, FEV1/FVC 44 +/- 15%, FEV1 reversibility 6.7 +/-
      9.1%, PaO2 8.8 +/- 1.1 kPa). Quality of life was measured by the St. George's
      Respiratory Questionnaire (SGRQ). Exacerbations (E) were assessed at acute visit
      (reported exacerbation) or from diary card data each month (unreported
      exacerbation). In 61 (87%) patients there were 190 exacerbations (median 3;
      range, 1 to 8) of which 93 (51%) were reported. There were no differences in
      major symptoms (increase in dyspnea, sputum volume, or purulence) or
      physiological parameters between reported and unreported exacerbations. At
      exacerbation, median peak flow fell by an average of 6.6 L/min (p = 0.0003).
      Using the median number of exacerbations as the cutoff point, patients were
      classified as infrequent exacerbators (E = 0 to 2) or frequent exacerbators (E =
      3 to 8). The SGRQ Total and component scores were significantly worse in the
      group that had frequent exacerbations: SGRQ Total score (mean difference = 14.8,
      p < 0.001), Symptoms (23.1, p < 0.001), Activities (12.2, p = 0.003), Impacts
      (13.9, p = 0.002). However there was no difference between frequent and
      infrequent exacerbators in the fall in peak flow at exacerbation. Factors
      predictive of frequent exacerbations were daily cough (p = 0.018), daily wheeze
      (p = 0.011), and daily cough and sputum (p = 0.009) and frequent exacerbations in
      the previous year (p = 0.001). These findings suggest that patient quality of
      life is related to COPD exacerbation frequency.

PMID- 9603118
TI  - Pulmonary artery remodeling differs in hypoxia- and monocrotaline-induced
      pulmonary hypertension.
AB  - In the present study we analyzed structural characteristics of muscular pulmonary
      arteries and arterioles in two classic models of pulmonary hypertension, the rat
      hypoxia and monocrotaline models. We hypothesized that an increase in medial
      cross-sectional area would result in reduction of the lumen area and that these
      parameters would correlate with the increase in pulmonary artery pressure (PAP).
      Four weeks after a single injection of monocrotaline (MCT) or after 4 wk of
      hypoxic exposure the rats were killed. Both MCT and chronic hypoxia induced right
      ventricular hypertrophy. In separate groups of rats both MCT and chronic hypoxia
      increased PAP. MCT increased the media cross-sectional area of pulmonary arteries
      with an external diameter between 30-100 microm and 101-200 microm and reduced
      the lumen area of pulmonary arteries with an external diameter between 101-200
      microm. Chronic hypoxia only slightly increased the media cross-sectional area
      without a change of the lumen area. Both MCT and hypoxia increased the percentage
      of partly muscularized and muscularized arterioles. The angiotensin-converting
      enzyme (ACE) inhibitor captopril (0.5 mg/kg/h) had no effect on MCT-induced
      pulmonary hypertension, right ventricular hypertrophy, and pulmonary artery
      remodeling. In chronic hypoxic rats it prevented an increase in medial cross
      sectional area of pulmonary arteries with an external diameter between 30-100
      microm and attenuated the increase in the percentage of muscularized arterioles,
      without any effect on the PAP. We conclude that MCT, in contrast to chronic
      hypoxia, induces structural changes of muscular pulmonary arteries with an
      external diameter between 101-200 microm which may contribute to an increased PAP
      and right ventricular hypertrophy. These data also suggest that angiotensin II
      plays a pivotal role in remodeling of pulmonary arteries in hypoxia but not in
      MCT-induced pulmonary hypertension.

PMID- 9603119
TI  - Inhibition of human airway sensitization by a novel monoclonal anti-IgE antibody,
      17-9.
AB  - We investigated the effect of a novel mouse IgG2b nonanaphylactogenic anti-human
      IgE antibody, 17-9, on allergen and histamine responses in passively sensitized
      human airways in vitro to determine the specific contribution of IgE to the
      sensitization process. Bronchial rings were sensitized with serum containing high
      levels of allergen-specific IgE (Dermatophagoides farinae), or with a hapten
      specific chimeric humanized IgE (JW8). There was a concentration-dependent
      contraction of serum-sensitized bronchial rings to D. farinae (517 +/- 188 mg
      tension at 10 U/ml, n = 8) that was not observed in nonsensitized controls. This
      response was practically abolished when tissues were sensitized in the presence
      of 100 microg/ml anti-IgE antibody 17-9 (54 +/- 20 mg). In tissues sensitized
      with the anti-NIP IgE, JW8, there was a concentration-dependent contraction to
      the specific antigen NIP-BSA (560 +/- 154 mg at 0.3 microg/ml, n = 5) that was
      not observed in nonsensitized control subjects and that was substantially
      inhibited when 17-9 was present in the sensitization buffer (124 +/- 109 mg). The
      inhibition with 17-9 was specific, as pretreatment with a non-IgE-specific IgG2b
      antibody did not affect allergen responses. Potency and maximal contractions to
      histamine in serum-sensitized tissues were significantly elevated compared with
      nonsensitized controls; this was not affected by the presence of 17-9 during
      sensitization (pEC50 = 5.1 +/- 0.2 versus 5.0 +/- 0.3 in tissues sensitized in
      the absence of 17-9). In tissues sensitized with JW8 there was no significant
      increase in responsiveness to histamine. We conclude that allergen responses in
      sensitized human airways are dependent on IgE levels in the sensitizing serum
      while nonspecific (hyper)responsiveness depends on serum factors other than IgE.
      Nonanaphylactogenic anti-human IgE antibodies effectively inhibit allergen
      responses of human airways in vitro but may not affect other factors inducing
      hyperresponsiveness.

PMID- 9603120
TI  - Once-weekly rifapentine-containing regimens for treatment of tuberculosis in
      mice.
AB  - The bactericidal activities of several once-weekly rifapentine (P)-containing
      combination regimens against Mycobacterium tuberculosis, and their ability to
      prevent the selection of rifampin (R)-resistant mutants, were compared with those
      of the standard six-times-weekly regimen consisting of R, isoniazid (H), and
      pyrazinamide (Z) in a mouse experiment. Mice were infected intravenously with 1.3
      x 10(7) cfu of M. tuberculosis strain H37Rv, and 8 wk of treatment began on Day
      14 after infection, when mice were randomly allocated to an untreated control
      group and nine treatment groups of 30 mice each. At the end of 8 wk of treatment,
      all the tested regimens showed promising bactericidal activities. Once-weekly P
      alone was less bactericidal than six-times-weekly R alone; likewise, the once
      weekly P-containing combined regimens were less bactericidal than the six-times
      weekly standard regimen. However, the difference in killing was about 1 log10,
      which represented only a fraction of the overall 4 log10 to 5 log10 magnitude of
      killing effects. The addition of streptomycin (S) improved the bactericidal
      effect of once-weekly PHZ, and the effect of once-weekly PHZS was further
      enhanced when it was preceded by 2 wk of daily HZS. The latter regimen achieved
      the same level of activity as the standard six-times-weekly regimen. All of the
      once-weekly P-containing combined regimens were able to prevent the selection of
      R-resistant mutants, whereas monotherapy with R or P selected resistant mutants
      in approximately 50% of animals.

PMID- 9603121
TI  - Systemic corticosteroids decrease the effectiveness of talc pleurodesis.
AB  - Corticosteroids can inhibit the inflammatory process and the formation of
      fibrosis. The purpose of this study was to determine whether the concurrent use
      of steroids at the time of talc-slurry pleurodesis would influence the
      development of the pleurodesis. One group of rabbits received an intrapleural
      injection of talc (400 mg/kg) and an intramuscular injection of triamcinolone
      (0.8 mg/kg) 1 d before talc instillation and weekly thereafter, whereas a control
      group received only talc. Ten rabbits in each group were killed at 6 h and at 1,
      2, 4, 7, 14, and 28 d after instillation. The mean volume of pleural fluid was
      significantly lower in the group receiving corticosteroids at 6 h through 4 d
      after talc slurry than in the other groups. The degree of pleural adhesion was
      significantly smaller in the group receiving corticosteroids from Day 2 through
      Day 28. At Day 28, all 10 rabbits that received talc only had a pleurodesis score
      of 3 or 4, whereas only four of the 10 rabbits that also received steroids had a
      pleurodesis score of 3 or 4. This study shows that the use of corticosteroids at
      the time of talc-slurry pleurodesis markedly decreases the inflammatory reaction
      to the talc, and essentially prevents a pleurodesis from developing.

PMID- 9603122
TI  - Segregation analysis of pulmonary function among families in the Framingham
      Study.
AB  - Familial aggregation of cross-sectional pulmonary function was examined in 5,003
      subjects from 1,408 families participating in the Framingham Study. Subjects, who
      were members of either the Original Cohort (recruited from 1948 to 1952) or the
      Offspring Cohort (recruited from 1971 to 1974), underwent spirometry at a mean
      age of 53 yr. The effects of age, height, weight, and smoking status on FEV1 were
      evaluated through linear-regression analysis, with separate models for men and
      women in each cohort. The gender- and cohort-specific standardized residual FEV1
      from these models was used as the phenotypic variable in familial correlation and
      segregation analyses to assess inheritance patterns. In models that assumed no
      major gene determining FEV1, correlation of pulmonary function was greater for
      mothers and offspring than for fathers and offspring (p[mo] = 0.190, p[fo] =
      0.112; p = 0.06), and sibling correlation exceeded parent-offspring correlation
      (p[sib] = 0.225; p < 0.01). By comparison with a general model, in which
      transmission probabilities and residual familial correlations are arbitrary,
      models that imposed a Mendelian gene were rejected (p < 0.001). A model with no
      parent-offspring transmission of a major factor, but with residual familial
      correlation, provided as good a fit as the general model, suggesting that
      environmental and/or polygenic genetic influences determine FEV1.

PMID- 9603123
TI  - Polycythemia impairs vasodilator response to acetylcholine in patients with
      chronic hypoxemic lung disease.
AB  - To investigate whether polycythemia associated with chronic hypoxemic lung
      disease (CHLD) increases vascular resistance by altering endothelium-derived
      nitric oxide (NO), we examined the responses to acetylcholine (ACh) infusions (5,
      10, and 15 mg/min) on hemodynamics and gas exchange in 21 patients with CHLD of
      varying severity. Patients were classified into two groups based on whether their
      hemoglobin (Hb) level was less or greater than 15.5 g/dl. In the normocythemic
      patients (Hb = 13.6 +/- 0.3 g/100 ml, n = 10), ACh decreased pulmonary artery
      pressure (Ppa) from 30 +/- 2 mm Hg 26 +/- 2 mm Hg (p < 0.01); pulmonary vascular
      resistance (PVR), from 5.1 +/- 0.4 U/m2 to 3.4 +/- 0.3 U/m2 (p < 0.001); systemic
      arterial pressure (Psa), from 111 +/- 4 mm Hg to 108 +/- 4 mm Hg (p < 0.05); and
      systemic vascular resistance (SVR), from 27 +/- 2 U/m2 to 22 +/- 2 U/m2 (p <
      0.01); and also increased the cardiac index (CI), from 3.8 +/- 0.2 to 4.7 +/- 0.3
      L/min/m2 (p < 0.001). PaO2 fell from 59 +/- 3 mm Hg to 48 +/- 3 mm Hg (p < 0.001)
      whereas venous admixture (Qs/Qt) rose from 32 +/- 4% to 44 +/- 4% (p < 0.01). In
      contrast, in patients with polycythemia (17.7 +/- 0.5 g/100 ml, n = 11) ACh
      failed to produce any changes in PaO2 (49 +/- 2 mm Hg versus 51 +/- 2 mm Hg, p =
      NS), Ppa (34 +/- 1 mm Hg versus 33 +/- 1 mm Hg, p = NS), PVR (6.7 +/- 0.9 U/m2
      versus 6.9 +/- 0.8 U/m2, p = NS) or Psa, but slightly increased the CI, from 3.6
      +/- 0.3 L/min/m2 to 3.9 +/- 0.3 L/min/m2 (p < 0.01), and Qs/Qt, from 40 +/- 4% to
      45 +/- 3% (p < 0.05). In the 21 patients, negative correlations with Hb
      concentrations were found for ACh-induced changes in PVR (r = -0.57, p < 0.01),
      Ppa (r = -0.46, p < 0.01), CI (r = -0.5, p < 0.05), PaO2 (r = -0.79, p < 0.01),
      and Qs/Qt (r = -0.79, p < 0.01). In the six polycythemic patients who received
      isovolemic hemodilution, with a decrease in Hb concentration from 18.6 +/- 0.9
      g/dl to 15.3 +/- 0.3 g/dl as a result, infusion of ACh, which was without effect
      before hemodilution, caused decreases in Ppa from 28 +/- 1 mm Hg to 23 +/- 1 mm
      Hg (p < 0.05) and in PVR from 5.7 +/- 0.8 U/m2 to 3.6 +/- 0.5 U/m2 (p < 0.02), as
      well as an increase in CI from 3.4 +/- 0.4 L/min/ m2 to 4.1 +/- 0.4 L/min/m2 (p <
      0.05). In contrast to ACh, inhaled NO (40 ppm) induced pulmonary vasodilation in
      both the normocythemic and polycythemic groups. Our results show that high
      hematocrit (Hct) levels inhibit endothelium-dependent vasodilation in response to
      ACh in patients with CHLD, possibly through inactivation of endothelial-derived
      NO by Hb.

PMID- 9603124
TI  - Detection of flow limitation with a nasal cannula/pressure transducer system.
AB  - We previously showed that upper airway resistance can be inferred from the
      inspiratory flow contour during continuous positive airway pressure (CPAP)
      titration in obstructive sleep apnea syndrome (OSAS). The present study examines
      whether similar information can be obtained from inspiratory flow measured by a
      nasal cannula/pressure transducer. Ten symptomatic patients (snoring, upper
      airway resistance syndrome [UARS], or OSAS) and four asymptomatic subjects
      underwent nocturnal polysomnography (NPSG) with monitoring of flow (nasal
      cannula) and respiratory driving pressure (esophageal or supraglottic catheter).
      For each breath the inspiratory flow signal was classified as normal, flattened,
      or intermediate by custom software. "Resistance" was calculated from peak
      inspiratory flow and pressure, and normalized to the resistance during quiet
      wakefulness. Resistance in all stages of sleep was increased for breaths with
      flattened (387 +/- 188%) or intermediate (292 +/- 163%) flow contour. In
      combination with apnea-hypopnea index (AHI), identification of "respiratory
      events," consisting of consecutive breaths with a flattened contour, allowed
      differentiation of symptomatic from asymptomatic subjects. Our data show that
      development of a plateau on the inspiratory flow signal from a nasal cannula
      identifies increased upper airway resistance and the presence of flow limitation.
      In patients with symptoms of excessive daytime somnolence and low AHI this may
      help diagnose the UARS and separate it from nonrespiratory causes of sleep
      fragmentation.

PMID- 9603125
TI  - A "closed" medical intensive care unit (MICU) improves resource utilization when
      compared with an "open" MICU.
AB  - We hypothesized that a "closed" intensive care unit (ICU) was more efficient that
      an "open" one. ICU admissions were retrospectively analyzed before and after ICU
      closure at one hospital; prospective analysis in that ICU with an open ICU nearby
      was done. Illness severity was gauged by the Mortality Prediction Model (MPM0).
      Outcomes included mortality, ICU length of stay (LOS), hospital LOS, and
      mechanical ventilation (MV). There were no differences in age, MPM0, and use of
      MV. ICU and hospital LOS were lower when "closed" (ICU LOS: prospective 6.1
      versus 12.6 d, p < 0.0001; retrospective 6.1 versus 9.3 d, p < 0.05; hospital
      LOS: prospective 19.2 versus 33.2 d, p < 0.008; retrospective 22.2 versus 31.2 d,
      p < 0.02). Days on MV were lower when "closed" (prospective 2.3 versus 8.5 d, p <
      0.0005; retrospective 3.3 versus 6.4 d, p < 0.05). Pooled data revealed the
      following: MV predicted ICU LOS; ICU organization and MPM0 predicted days on MV;
      MV and ICU organization predicted hospital LOS; mortality predictors were open
      ICU (odds ratio [OR] 1.5, p < 0.04), MPM0 (OR 1.16 for MPM0 increase 0.1, p <
      0.002), and MV (OR 2.43, p < 0.0001). We conclude that patient care is more
      efficient with a closed ICU, and that mortality is not adversely affected.

PMID- 9603126
TI  - Bronchoalveolar lavage cellularity: lone cryptogenic fibrosing alveolitis
      compared with the fibrosing alveolitis of systemic sclerosis.
AB  - Lone cryptogenic fibrosing alveolitis (CFA) is histologically identical to
      fibrosing alveolitis associated with systemic sclerosis (FASSc), but it has a
      much worse prognosis after matching for disease severity at presentation. The
      aims of this study were to gain insights into possible pathogenetic mechanisms
      contributing to this prognostic difference, by comparing bronchoalveolar lavage
      (BAL) cellularity in the two diseases, and to evaluate the relationships between
      BAL findings and the regional and global extent of disease, quantified by thin
      section computed tomography (CT) and lung function indices. Patients with CFA
      were distinguished by more extensive fibrosing alveolitis on CT (p < 0.02) and by
      higher counts of neutrophils (total per ml, p < 0.02; percentage p < 0.03) and
      eosinophils (total per ml, p < 0.002; percentages, p < 0.02) in BAL fluid. After
      adjustment for functional and morphologic measures of disease extent, eosinophil
      percentages and total counts were increased in CFA (p < 0.05 in all 12
      multivariate models), but they were not independently related to regional or
      global disease severity. Neutrophil percentages and total counts were virtually
      identical in CFA and FASSc in disease of comparable severity, and they increased
      with increasingly extensive lobar disease and global disease, as judged by CT, p
      < 0.0005 in all analyses. Neutrophil levels were more closely linked to the
      extent of disease on CT than to the severity of functional impairment, on
      univariate and multivariate analysis. The higher BAL eosinophil levels seen in
      CFA, compared with those seen in FASSc, after adjustment for disease extent,
      indicate that an eosinophilic influx may be linked to the pathogenesis of
      fibrosing alveolitis. By contrast, BAL neutrophil levels increase with
      increasingly extensive disease on CT, but they do not differ independently
      between CFA and FASSc, suggesting that neutrophil degradation products are
      unlikely to account for the excess mortality in CFA, compared with that in FASSc.

PMID- 9603127
TI  - Inhaled nitric oxide in acute respiratory distress syndrome: a pilot randomized
      controlled study.
AB  - This pilot randomized controlled clinical trial of patients with ARDS was
      implemented to study the impact of inhaled nitric oxide (inhNO) on lung function,
      morbidity, and mortality. Thirty patients with ARDS were randomly allocated to
      usual care or usual care plus inhNO. The optimal dose of inhNO was determined to
      be between 0.5 and 40 parts-per-million daily. All therapeutic interventions were
      standardized. ARDS resulted mainly from sepsis (25 of the 30). During the first
      24 h, the hypoxia score increased greatly in patients treated with inhNO +70.4 mm
      Hg (+59%) versus +14.2 mm Hg (+9.3%) for the control group (p = 0.02), venous
      admixture decreased from 25.7 to 15.2% in the inhNO group, and from only 19.4 to
      14.9% in the control group (p = 0.05). After the first day of therapy no further
      beneficial effect of inhNO was detected. Forty percent of the patients treated
      with inhNO were alive and weaned from mechanical ventilation within 30 d after
      randomization compared with 33.3% in the control group (p = 0.83). The 30-d
      mortality rate was similar in the two groups; most deaths (11 of 17) were due to
      multiple organ dysfunction syndrome. This study shows that inhNO, in this
      population, may improve gas exchange but does not affect mortality.

PMID- 9603128
TI  - General exercise training improves ventilatory and peripheral muscle strength and
      endurance in chronic airflow limitation.
AB  - We studied the impact of a 6-wk supervised, multimodality endurance exercise
      training program (EXT) on strength and endurance of ventilatory and peripheral
      muscles in patients with chronic airflow limitation (CAL), and determined whether
      potential improvements contributed to relief of exertional breathlessness (B) and
      perceived leg effort/discomfort (LE), respectively. Twenty breathless patients
      with stable CAL (FEV1 = 41 +/- 3% predicted; mean +/- SEM) were tested at 6-wk
      intervals at baseline, after a nonintervention control period (pre-EXT), and post
      EXT. Measurements included: pulmonary function tests (PFTs), maximal
      inspiratory/expiratory pressures (MIP, MEP), inspiratory muscle endurance
      (V(LIM)), quadriceps strength and endurance, exercise endurance, and submaximal
      cycle exercise with cardioventilatory and symptom responses. Measurements at
      baseline and pre-EXT were identical. Post-EXT, PFTs did not change; exercise
      endurance measured on the treadmill, cycle ergometer, arm ergometer, and by 6-min
      walk distance increased 40 +/- 8%, 43 +/- 10%, 12 +/- 5%, and 34 +/- 9%,
      respectively (p < 0.05); quadriceps strength increased 21 +/- 5% (p < 0.01); MIP
      and MEP increased 29 +/- 11% and 27 +/- 11%, respectively (p < 0.05); V(LIM)
      increased almost threefold (p < 0.05). At isotime near end-exercise, B, LE,
      carbon dioxide production (VCO2), oxygen consumption (VO2), ventilation, and
      breathing frequency (F) all fell after EXT (p < 0.05): deltaB correlated with
      deltaF (r = 0.58, p < 0.01). Increased MIP and V(LIM) did not correlate with
      improved breathlessness or exercise endurance. Similarly, changes in quadriceps
      strength and endurance did not correlate with changes in LE or exercise
      endurance. In conclusion, general nonspecific EXT improved ventilatory and
      peripheral muscle function in severe CAL, but such improvements did not appear to
      contribute significantly to reduced exertional symptoms and enhanced exercise
      performance.

PMID- 9603129
TI  - Bronchial microbial patterns in severe exacerbations of chronic obstructive
      pulmonary disease (COPD) requiring mechanical ventilation.
AB  - We carried out a comprehensive microbiological study of the upper and lower
      airways in patients with severe exacerbations of chronic obstructive pulmonary
      disease (COPD) requiring mechanical ventilation in order to describe microbial
      patterns and analyze their clinical significance. Quantitative cultures of
      tracheobronchial aspirates (TBAs), bronchoscopically retrieved protected specimen
      brush (PSB) and bronchoalveolar lavage fluid (BALF) at admission to the ICU and
      after 72 h, as well as serology for bacteria and respiratory viruses were
      performed. Fifty patients (mean age 68 +/- 8, 46 males) were studied
      prospectively. Potentially pathogenic microorganisms (PPMs) and/or a positive
      serology were present in 36 of 50 (72%) patients, including 12 (33%)
      polymicrobial cases. Only six (12%) had no pathogen in any sample in the absence
      of antimicrobial pretreatment. Microbial patterns corresponded to community
      acquired pathogens (Streptococcus pneumoniae, Haemophilus influenzae, and
      Moraxella catarrhalis) in 19 of 34 (56%) and to gram-negative enteric bacilli
      (GNEB), Pseudomonas, and Stenotrophomonas spp. in 15 of 34 (44%) of isolates.
      Chlamydia pneumoniae and respiratory viruses were found in 18% and 16% of
      investigations, respectively. Repeated investigation after 72 h in 19 patients
      with PPMs in the initial investigation revealed eradication of virtually all
      isolates of community-acquired pathogens and GNEB but persistence of three of
      five Pseudomonas spp. and both Stenotrophomonas spp. as well as the emergence of
      new GNEB, Pseudomonas and Stenotrophomonas spp. Clinical parameters neither
      predicted the presence of PPMs nor of GNEB and Pseudomonas/Stenotrophomonas spp.
      Nevertheless, severe pneumonia attributable to initially isolated pathogens
      occurred in two patients with severe COPD exacerbation. We conclude that
      pathogens were more frequently present than previously reported. The rate of GNEB
      and Pseudomonas/Stenotrophomonas spp. isolates was high. The presence of
      pathogens was clinically unpredictable. Thus, in this population of patients with
      severe exacerbations of COPD, it may be advisable to obtain respiratory samples
      and to treat according to diagnostic results. Further studies are warranted to
      clarify this issue.

PMID- 9603130
TI  - Human respiratory syncytial virus produces prolonged alterations of neural
      control in airways of developing ferrets.
AB  - A dysfunction of pathways that normally cause contraction or relaxation of
      airways has been proposed to explain heightened levels of responsiveness produced
      by various insults to the airway. For example, we previously reported (4) that
      infection of cotton rats with the human respiratory syncytial virus (HRSV) leads
      to a significant decrease in an airway's nonadrenergic noncholinergic inhibitory
      (NANCi) response shortly after the infection. In the present study we addressed
      the more chronic effects of HRSV infection on airway function in young ferrets
      during a period of rapid somatic growth. Animals 1 wk old received HRSV or
      uninfected cell culture medium intranasally. In vitro studies of airway function
      were performed on tracheal smooth muscle (TSM) segments at 4, 8, and 24 wk of
      age. To evaluate neurally mediated contractile responses, frequency-response
      curves to electrical field stimulation (EFS) were performed with results
      expressed in terms of the frequency causing 50% of the maximal contractile
      response (ES50). In addition, contractile responses of TSM to methacholine (MCh)
      were also assessed with results expressed as the concentration needed to produce
      50% of the maximal contractile response (EC50). To gauge NANCi responses, TSM was
      contracted with neurokinin A in the presence of atropine, propranolol, and
      indomethacin. Relaxant responses to EFS were assessed at frequencies from 5 to 30
      Hz, with results expressed as mean percent relaxation. We found increased
      contractile responses to EFS in infected animals compared with that in the
      control group in both 4- and 8-wk old animals (p = 0.001 and p = 0.008,
      respectively). This difference had resolved by 24 wk of age. There was no
      difference in TSM responses to MCh between the groups at any age. Although there
      were no NANCi responses in 4-wk-old ferrets from either group, NANCi responses
      were significantly decreased in 8-wk-old ferrets previously infected with HRSV in
      the first week of life (p = 0.0001). A significant difference persisted (p =
      0.008), albeit to a lesser degree, at 24 wk of age. These findings demonstrate
      that HRSV produces prolonged alterations of TSM function in ferret airways in
      vitro.

PMID- 9603131
TI  - Effect of route of breathing on response to exposure in a swine confinement
      building.
AB  - Exposure of naive subjects to swine buildings results in acute nasal, lung, and
      peripheral blood inflammatory responses with an increase in nonallergic airway
      responsiveness. Because nasal passages filter large particles and soluble gases
      and because swine building exposure results in an acute inflammatory response at
      this level, we questioned what effect breathing through or avoiding this route
      would have on local and systemic inflammation. Nine normal young men 23 to 37 yr
      of age were exposed for 5 h to a swine building, once breathing normally and once
      with the mouth occluded (n = 8) (Protocol 1) or the nose occluded (n = 4)
      (Protocol 2); three subjects participated in both protocols. For each protocol
      each subject underwent a methacholine challenge for PC20 measurement, a nasal
      lavage, venous blood puncture, and a bronchoalveolor lavage (BAL) once before and
      once after each swine building exposure. Bronchial responsiveness as measured by
      PC20 decreased in most subjects after swine building exposure and was not
      influenced by the route of breathing. Nasal lavage neutrophils increased tenfold
      after each swine exposure, except when the nose was occluded where no alteration
      was observed. Total BAL cells significantly increased after each exposure to the
      swine building, this increase was not modified by the route of breathing. In
      Protocol 1, white blood cells increased from a baseline level of 7.0 to 10.5 x
      10(9) cells/L after exposure with normal breathing and to 10.7 x 10(9) cells/L
      during nasal breathing exclusively. For Protocol 2, these respective values were:
      5.6, 11.7 and 10.4 x 10(9)/L. Interleukins 6 and 8 levels in BAL, nasal washes,
      and serum were increased by swine building exposure, except in the nasal wash
      when the nose was occluded. In conclusion, the lung and blood responses to
      exposure in a swine confinement building are not modified by the route of
      breathing, suggesting that nasal inflammation and filtration are not important in
      the process and that small respirable particles and/or gases may be responsible
      for these responses.

PMID- 9603132
TI  - Surface tension forces in sleep apnea: the role of a soft tissue lubricant: a
      randomized double-blind, placebo-controlled trial.
AB  - Upper airway obstruction in patients with sleep apnea may occur in the absence of
      a negative intraluminal upper airway pressure. We hypothesized that surface
      tension forces may play a role in the pathogenesis of obstructive sleep apnea
      (OSA), and that a topical soft tissue lubricant might reduce the severity of OSA.
      Ten male patients (age 49 +/- 10 yr [mean +/- SD]; body mass index [BMI] 31 +/- 5
      kg/m2) with OSA (apnea-hypopnea index [AHI] 17 +/- 9) were studied. The arousal
      index was lower with the lubricant treatment than with placebo (mean difference
      8; 95% CI 4 to 11 arousals/h; p = 0.001). The AHI was lower, in each of the 10
      patients, on the lubricant treatment than the placebo (mean change 10, 95% CI 6
      to 13; p = 0.0003). The lower AHI with lubricant as compared with placebo was
      present in both supine (mean difference 13; 95% CI 5 to 20; p = 0.006) and
      nonsupine (mean difference 6; 95% CI 0 to 12; p = 0.05) positions. There was no
      significant difference in sleep architecture between the lubricant and placebo
      treatments. Application of a topical lubricant consistently reduced the severity
      of OSA. This implies a pathogenetic role for surface tension forces in OSA, and a
      potential role for surface tension-reducing agents in the treatment of OSA.

PMID- 9603133
TI  - Assessment of airflow obstruction during CPAP by means of forced oscillation in
      patients with sleep apnea.
AB  - The forced oscillation technique (FOT) is a noninvasive method to measure
      respiratory resistance (Rrs) potentially useful for monitoring upper airway
      obstruction in patients with obstructive sleep apnea/hypopnea syndrome (SAHS).
      The aim of this work was to test the clinical suitability of FOT in assessing
      dynamic changes in airflow obstruction in patients with SAHS during continuous
      positive airway pressure (CPAP) and to investigate the CPAP dependence of Rrs.
      Forced oscillation (5 Hz) was applied to six male patients with SAHS submitted to
      CPAP titration procedure. Esophageal pressure was measured with a balloon-tipped
      catheter. Mid-inspiratory resistance (Rrs,i), mid-expiratory resistance (Rrs,e),
      and esophageal pressure swings (deltaPes) were computed for the respiratory
      events recorded at each CPAP level. Rrs,i decreased markedly and significantly
      from 36.0 +/- 4.0 cm H2O x s/L (mean +/- SEM) at baseline CPAP (4 cm H2O) to 13.1
      +/- 2.8 cm H2O x s/L at optimal CPAP (11.3 +/- 0.4 cm H2O). Rrs,e showed a faster
      decrease with increasing CPAP reaching normal values at approximately 8 cm H2O.
      Rrs,i was strongly correlated (r2 = 0.94) with deltaPes. Our results suggest that
      FOT can be used as an alternative to the esophageal balloon for assessing airflow
      obstruction in patients with SAHS and for CPAP titration. Moreover, FOT allows us
      to detect phasic changes in resistance within the breathing cycle.

PMID- 9603134
TI  - Tazanolast inhibits ozone-induced airway hyperresponsiveness in guinea pigs.
AB  - We studied the inhibitory effect of tazanolast, a selective mast-cell-stabilizing
      drug, on ozone-induced airway hyperresponsiveness in guinea pigs. Airway
      responsiveness to methacholine peaked at 2 h after ozone exposure (2.0 ppm for 2
      h) and the number of neutrophils in bronchoalveolar lavage (BAL) fluid continued
      to increase until 6 h. Tazanolast administered before ozone exposure at doses of
      30, 100, or 300 mg/kg inhibited ozone-induced airway hyperresponsiveness in a
      dose-dependent manner. However, tazanolast administered after ozone exposure did
      not inhibit the airway hyperresponsiveness. Tazanolast did not significantly
      change the cell distribution of BAL cells at 2 h after the exposure. We conclude
      that tazanolast significantly inhibits ozone-induced airway hyperresponsiveness
      in guinea pigs. This result suggests that mast cells may play an important role
      in its development.

PMID- 9603135
TI  - Limitations of a home characteristics questionnaire as a predictor of indoor
      allergen levels.
AB  - We examined associations between reported home characteristics and levels of
      indoor allergens in 499 homes of a birth cohort of children of allergic/asthmatic
      families from the Boston area. The risk of having dust mite allergen (Der f 1 or
      Der p 1) > or = 2 microg/g on the bedroom floor was highest in houses, but 16% of
      apartments had levels this high. Compared with that from smooth floors, dust from
      carpeted bedroom floors had 2.1 times the risk of dust mite allergen > or = 10
      microg/g, but levels exceeded 2 microg/g in 32% of uncarpeted floors. The risk of
      dust mite allergen > or = 10 microg/g of dust from plastic-encased mattresses was
      0.5 times that for cloth mattresses, but levels in 21% of plastic-encased
      mattresses were > or = 2 microg/g. In 93% of homes with and 3% of homes without
      cats, Fel d 1 was > or = 8 microg/g, but 34% of homes without cats had Fed d 1 >
      or = 1 microg/g. Cockroach allergen (Bla g 1 or Bla g 2) was > or = 2 U/g of
      kitchen dust in 26% of apartments and only 6% of houses, and it was detected in
      48% of homes with no reported signs of cockroaches in the previous 12 mo. Home
      characteristics reporting is a relatively weak predictor of the absence of
      allergen, and exposure can occur even when no cats are present, beds are encased
      in plastic, no carpets are present, and no signs of cockroaches have been
      reported.

PMID- 9603136
TI  - Endogenous nitric oxide and the pulmonary microvasculature in healthy sheep and
      during systemic inflammation.
AB  - Nitric oxide (NO) influences microvascular integrity. NO synthase inhibitors are
      regarded as therapeutic options, but their impact on the pulmonary
      microvasculature is not well defined. We studied the microvascular effects of the
      nonselective NO synthase inhibitor N(omega)-nitro L-arginine methylester (L-NAME)
      in healthy sheep and during systemic inflammation. Permeability analysis was
      performed in 30 adult ewes with chronic lung lymph fistulas and pulmonary venous
      occluders. Experiment 1: 20 sheep received Escherichia coli endotoxin
      (lipopolysaccharide, 10 ng/kg/min) for 32 h. After 24 h of endotoxemia, 10 sheep
      were given L-NAME (25 mg/kg), and 10 sheep received NaCl 0.9%. Experiment 2: six
      sheep were treated with L-NAME (25 mg/kg), and four animals received NaCl 0.9%.
      Endotoxin induced a phasic pulmonary microvascular response with early
      transiently increased endothelial permeability at 4 h and late normalization of
      microvascular integrity to large molecules after 24 h. At that time systemic
      vasodilation had occurred. L-NAME raised pulmonary artery pressure and pulmonary
      vascular resistance index without signs of increased permeability in either
      experiment. NO is involved in vascular tone in healthy sheep and during systemic
      inflammation, but it does not seem to play a role in the integrity of the
      pulmonary microvascular barrier function to large molecules.

PMID- 9603137
TI  - Cholestatic liver injury increases circulating TNF-alpha and IL-6 and mortality
      after Escherichia coli endotoxemia.
AB  - We employed a bile duct ligation (BDL) model of cholestatic liver injury to test
      the hypothesis that this form of preexisting hepatic dysfunction alters the
      kinetics of circulating TNF-alpha and IL-6 after Escherichia coli endotoxemia,
      thereby augmenting mortality and lung injury by a TNF-alpha:leukotriene (LT) axis
      of inflammation. Male rats were catheterized 13 d after BDL or sham surgery and
      studied while awake 18 to 24 h later. Cholestasis after BDL was confirmed by
      baseline serum bilirubin (BDL = 7.34 +/- 0.72 mg/dl, mean +/- SEM, n = 17 versus
      Sham = 0.25 +/- 0.07, n = 20; p < 0.005) and histopathology. Sham and BDL animals
      received E. coli lipopolysaccharide serotype O55:B5 (LPS, 5 mg/kg i.v.) or 0.9%
      NaCl (NS) ending at t = 0 and were monitored over 24 h for vital signs and
      hemodynamics. In parallel studies, lipoxygenase inhibition was performed using
      diethylcarbamazine or the 5-lipoxygenase activating-protein inhibitor MK-886.
      Blood was collected at baseline and at t = 1.5, 3.5, and 24 h for formed elements
      and for serum endotoxin, TNF-alpha, IL-6, bilirubin, and alanine aminotransferase
      (ALT). Organs were evaluated at 24 h for histopathology, including neutrophil
      (PMN) densities and wet/dry weight (W/D) ratios. Cholestasis reduced survival
      after otherwise nonlethal endotoxemia, with seven of 11 BDL + LPS rats dying
      within 24 h versus no deaths in BDL + NS (n = 6), Sham + LPS (n = 14), or Sham +
      NS (n = 6) animals (p < 0.01). Despite equivalent serum endotoxin between groups,
      circulating TNF-alpha was 8-fold higher in BDL + LPS than in Sham + LPS rats at
      1.5 and 3.5 h (p < 0.001), whereas serum TNF-alpha did not differ between BDL +
      NS and Sham + NS rats. IL-6 likewise was increased differentially by 1.5 h in BDL
      + LPS animals (11.98 +/- 2.42 ng/ml) versus Sham + LPS rats (3.05 +/- 0.58 ng/ml,
      p < 0.05). Hypothermia, bradycardic hypotension, and leukopenia were most severe
      and prolonged in BDL + LPS rats, which also had significantly higher ALT values,
      W/D ratios, and organ PMN counts. LT inhibition failed to reduce BDL-related
      differences in serum cytokines or survival after endotoxemia. Thus, cholestasis
      augments inflammatory responses to gram-negative endotoxemia, sensitizing the
      host to enhanced fluid flux in multiple organs and to mortality by a LT
      independent mechanism.

PMID- 9603138
TI  - The effects of 5-lipoxygenase inhibition by zileuton on platelet-activating
      factor-induced pulmonary abnormalities in mild asthma.
AB  - Platelet-activating factor (PAF) has been implicated in the pathogenesis of
      asthma. We investigated whether PAF-induced neutropenia and lung function
      disturbances are secondary to activation of the 5-lipoxygenase (5-LO) pathway
      with the consequent liberation of leukotrienes. The effect of a selective 5-LO
      inhibitor (zileuton) was examined in 10 mildly asthmatic patients (24 +/- 1 [mean
      +/- SE] yr; FEV1 = 94 +/- 4% predicted) before and after PAF inhalation, in a
      randomized, double-blind, placebo-controlled, crossover fashion. Patients were
      studied at baseline, 3 h after an oral single dose of zileuton (600 mg) or
      placebo, and then at 5 min, 15 min, and 45 min after PAF (18 microg) inhalation.
      Compared with vehicle, premedication with zileuton reduced both PAF-induced
      neutropenia at 5 min (by 43%) (p < 0.005) and the subsequent rebound neutrophilia
      at 15 min and 45 min (by 50% and 47%, respectively) (p < 0.025 each). In
      addition, at 5 min after PAF inhalation, zileuton attenuated increases in
      respiratory system resistance (Rrs) (by 39%) (p < 0.01) and in the alveolar
      arterial PO2 difference (A-a)PO2 (by 40%) (p < 0.05), and the decrease in PaO2
      (by 27%) (p < 0.005). The protective effect of zileuton against PAF-induced
      ventilation-perfusion (VA/Q) defects was shown by a parallel improvement
      (decrease) in an overall marker of VA/Q inequality (dispersion of retention minus
      excretion of inert gases corrected for dead space; DISP R-E.) (by 43%) 5 min
      after administration of PAF (p < 0.01). These findings indicate that PAF-induced
      systemic and pulmonary effects in patients with mild asthma are effectively
      mediated by the ongoing release of leukotrienes.

PMID- 9603139
TI  - Interleukin-8 and markers of neutrophil degranulation in pleural effusions.
AB  - In order to know the degree of interleukin-8 (IL-8) production in the pleural
      space and its relationship to neutrophil activation, IL-8, neutrophil elastase
      (NE), and myeloperoxidase (MPO) were assessed in blood and pleural fluid (PF) of
      219 patients with pleural effusions. Correlations between blood and PF IL-8, NE,
      and MPO were either absent or weak, except for IL-8 in transudates (r = 0.6745, p
      < 0.001). PF IL-8, NE, and MPO concentrations in cases of empyema were higher
      than in cases of effusion of other causes (p < 0.001). No significant differences
      in inflammatory markers were observed between parapneumonic and tuberculous
      fluids. IL-8, NE, and MPO levels in malignant, nonspecific, and transudative
      effusions were lower than in those due to infection, the lowest levels
      corresponding to transudates. No significant correlation was observed between PF
      IL-8 and neutrophil count in any group; in contrast, IL-8 was associated with NE
      and MPO in empyema (r = 0.7545, and r = 0.7283; p < 0.001), tuberculosis (r =
      0.4016, p = 0.008 and r = 0.6545, p < 0.001), and nonspecific effusions (r =
      0.3748, p = 0.007 and r = 0.3085, p = 0.028). Our results indicate that local
      production of markers of the nonspecific inflammatory response is high in both
      chronic and acute pleural infection, and suggest a role for IL-8 in the release
      of NE and MPO.

PMID- 9603140
TI  - Conductive and acinar lung-zone contributions to ventilation inhomogeneity in
      COPD.
AB  - We investigated ventilation inhomogeneity in patients with chronic obstructive
      pulmonary disease (COPD) through use of the multiple breath N2 washout test
      (MBW). From an alveolar slope analysis throughout the MBW, we derived two
      indices, S(cond) and S(acin), as a measure of ventilation inhomogeneity in
      conductive and acinar zones of the lungs, respectively (J. Appl. Physiol.
      1997;83:1807-1816). We evaluated the relationship of S(cond) and S(acin) to
      standard lung-function indices by means of a principal-components factor
      analysis, which linked correlated indices to independent factors accounting for
      81% of the total variance within the COPD group. S(acin) was linked to the so
      called acinar lung-zone factor, which also comprises diffusion capacity
      measurements. S(cond) was linked to the so-called conductive lung-zone factor,
      which also comprises specific airway conductance (S(Gaw)) and forced expiratory
      flows. FEV1 divided by FVC (FEV1/FVC) was the only variable linked to both the
      conductive and the acinar lung-zone factors. The fact that S(cond) and S(acin)
      were linked to independent factors provides statistical confirmation of the
      hypothesis that S(cond) and S(acin) reflect independent lung alterations, whereas
      FEV1/FVC behavior indicates a combined conductive and acinar contribution to
      airways obstruction.

PMID- 9603141
TI  - Effect of lung volume reduction surgery on diaphragm strength.
AB  - Since lung volume reduction surgery (LVRS) reduces end-expiratory lung volume, we
      hypothesized that it may improve diaphragm strength. We evaluated 37 patients for
      pulmonary rehabilitation and LVRS. Before and 8 wk after pulmonary
      rehabilitation, 24 patients had spirometry, lung volumes, diffusion capacity,
      incremental symptom limited maximum exercise test, 6-min walk test, maximal
      static inspiratory and expiratory mouth pressures, and transdiaphragmatic
      pressures during maximum static inspiratory efforts and bilateral supramaximal
      electrophrenic twitch stimulation measured. Twenty patients (including 7 patients
      who crossed over after completing pulmonary rehabilitation) had baseline
      measurements postrehabilitation, and 3 mo post-LVRS. Patients were 58 +/- 8 yr of
      age, with severe COPD and hyperinflation (FEV1, 0.69 +/- 0.21 L; RV, 4.7 +/- 1.4
      L). Nineteen patients had bilateral LVRS performed via median sternotomy and
      stapling, and 1 patient had unilateral LVRS via thorascopy with stapling. After
      rehabilitation, spirometry and DL(CO)/VA were not different, and lung volumes
      showed a slight worsening in hyperinflation. Gas exchange, 6-min walk distance,
      maximum oxygen uptake (VO2max), and breathing pattern during maximum exercise did
      not change after rehabilitation, but total exercise time was significantly
      longer. Inspiratory muscle strength (PImax, Pdi(max combined), Pdi(max sniff),
      Pdi(max), Pdi(twitch)), was unchanged after rehabilitation. In contrast, after
      LVRS, FVC increased 21%, FEV1 increased 34%, TLC decreased 13%, FRC decreased
      23%, and FRC(trapped gas) and RV decreased by 57 and 28%, respectively. PCO2 was
      lower (44 +/- 6 versus 48 +/- 6 mm Hg, p < 0.003) and 6-min walk distance
      increased (343 +/- 79 versus 250 +/- 89 m, p < 0.001), as did total exercise time
      during maximum exercise (9.2 +/- 1.9 versus 6.9 +/- 2.7 min, p < 0.01). Minute
      ventilation (29 +/- 8 versus 21 +/- 6 L/min, p < 0.001) and tidal volume (1.0 +/-
      0.33 versus 0.84 +/- 0.25 L, p < 0.001) during maximum exercise increased whereas
      respiratory rate was lower (28 +/- 6 versus 32 +/- 7 breaths/min, p < 0.02).
      Measurements of respiratory muscle strength (PImax, 74 +/- 28 versus 50 +/- 18 cm
      H2O, p < 0.002; Pdi(max combined), 80 +/- 25 versus 56 +/- 29 cm H2O, p < 0.01;
      Pdi(max sniff), 71 +/- 7 versus 46 +/- 27 cm H2O, p < 0.01; Pdi(twitch), 15 +/- 5
      versus 7 +/- 5 cm H2O, p < 0.01) were all greater post-LVRS. Inspiratory muscle
      workload as measured by Pdi TTI was lower following LVRS (0.07 +/- 0.02 versus
      0.09 +/- 0.03, p < 0.03). On multiple regression analysis, increases in PImax
      correlated significantly with decreases in RV and FRC(trapped gas) after LVRS (r
      = 0.67, p < 0.03). We conclude that LVRS significantly improves diaphragm
      strength that is associated with a reduction in lung volumes and an improvement
      in exercise performance. Future studies are needed to determine the relationship
      and stability of these changes over time.

PMID- 9603142
TI  - Abnormalities of gastric mucosal oxygenation in septic shock: partial
      responsiveness to dopexamine.
AB  - Splanchnic mucosal perfusion abnormalities have been implicated in the
      development of sepsis and multiorgan failure. We employed reflectance
      spectrophotometry for direct assessment of the microvascular hemoglobin oxygen
      saturation (HbiO2) and hemoglobin concentration (rel Hb(conc)) in the mucosa of
      the upper gastrointestinal tract. Owing to the high recording frequency together
      with a small catchment volume, assessment of spatial heterogeneity is enabled.
      Results were as follows: In healthy controls (n = 7), mean HbiO2 was 70.3 +/-
      2.1%, with narrow dispersion and near-Gaussian distribution of the histogram. In
      patients presenting with hyperdynamic septic shock (n = 15) mean HbiO2 was
      reduced to 51.0 +/- 1.6% in spite of high normal whole-body oxygen delivery, with
      tailing of the histogram to severely hypoxic values (18.4 % of data < 40%). In
      parallel, markedly reduced rel Hb(conc) values were recorded and the standardized
      intramucosal pH (pHi) was lowered to 7.25 +/- 0.01. Short-term infusion of
      dopexamine (2 microg/kg/min) caused a significant rise in HbiO2 and rel Hb(conc),
      whereas whole-body oxygen uptake and standardized pHi values were not altered. In
      conclusion, decreased oxygenation and tissue hemoglobin concentration, with the
      appearance of severely hypoxic microdomains, were noted in patients with
      hyperdynamic sepsis, strongly suggesting pronounced microcirculatory disturbances
      in this compartment. The partial responsiveness of these abnormalities to
      dopexamine warrants further elucidation.

PMID- 9603143
TI  - Lung volumes before and after lung volume reduction surgery: quantitative CT
      analysis.
AB  - The volume and severity of pulmonary emphysema in individual lungs were measured
      by means of quantitative computed tomography (CT) studies in 28 patients (14
      women, 14 men, median age 65 yr) who underwent either bilateral (n = 15) or
      unilateral (n = 13) lung volume reduction surgery (LVRS). Spirometric, total body
      plethysmographic, and CT data (at TLC and RV) were correlated before and after
      LVRS. Lung volumes determined by CT correlated well with volumes obtained by
      total body plethysmography (p < 0.0001). For individual lungs after LVRS, CT
      derived mean lung capacity decreased 13% and residual volume 20% (p < 0.00001 for
      each), while mean total functional lung volume (TFLV, defined as the volume of
      lung with CT attenuation greater than -910 Hounsfield units) increased 9% (p <
      0.01), and the mean ratio of the air space to tissue space volume (V(AS)/V(TS))
      decreased more at RV (23%) than at TLC (14%) (p < 0.0005 for each). In contrast,
      unilateral LVRS did not affect exhalation from the unoperated lung (2% reduction
      in RV, p = NS). The magnitude of the postoperative response (CT-derived TLC, RV,
      TFLV, V(AS)/V(TS)) of each operated lung was comparable for unilateral and
      bilateral LVRS. Thus, a lung's response to LVRS was independent from that of the
      contralateral lung. Moreover, postoperative alterations in TFLV and FEV1
      correlated significantly (r = 0.80, p < 0.0001), which suggests that the
      expansion of functioning tissue may contribute to the mechanism by which LVRS
      palliates airway obstruction.

PMID- 9603144
TI  - Appraising pulmonary edema using supine chest roentgenograms in ventilated
      patients.
AB  - The role of portable, anteroposterior, supine chest X-rays (CXRs) in
      distinguishing hydrostatic pulmonary edema (HPE) from permeability pulmonary
      edema (PPE) in mechanically ventilated patients is controversial. We
      prospectively obtained and evaluated such CXRs in 33 supine, mechanically
      ventilated intensive-care-unit patients with pulmonary artery catheters. Three
      chest radiologists independently reviewed CXRs without clinical information and
      recorded the cardiothoracic (CT) ratio, vascular pedicle width (VPW), and other
      radiographic features commonly used to evaluate pulmonary edema. Hydrostatic
      pulmonary edema was associated with a larger CT ratio (p < 0.001), subjective
      impressions of cardiomegaly (p < 0.01), and increased VPW (p = 0.02). There was a
      significant correlation between the pulmonary artery occlusion pressure and the
      VPW (r = 0.45, p = 0.0076) and CT ratio (r = 0.52, p = 0.0016), as well as
      between the VPW and CT ratio (r = 0.49, p = 0.0032). Despite this detailed
      evaluation of the CXRs, the mean accuracy of the radiologists' clinical diagnosis
      of HPE versus PPE was 41%, and 15 of 19 (79%) of PPE patients showed one or more
      roentgenographic signs of volume overload. Receiver-operating-characteristic
      curves were constructed to determine optimum cut-off values of VPW and CT ratio
      associated with HPE. Hydrostatic pulmonary edema was found to correlate best
      using a VPW > 63 mm coupled to a CT ratio > 0.52 (p = 0.027). With this
      combination of objective criteria, radiologists' diagnostic accuracy could have
      been increased to 73%. We therefore conclude that measurements of CT ratio and
      VPW correlate with pulmonary artery occlusion pressure in supine, mechanically
      ventilated patients. Distinction of hydrostatic from permeability pulmonary edema
      is difficult using portable, supine CXRs, but readily assessed radiologic signs
      may contribute to the correct diagnosis.

PMID- 9603145
TI  - Preliminary results of collapse therapy with plombage for pulmonary disease
      caused by multidrug-resistant mycobacteria.
AB  - Seven patients underwent collapse therapy with polystyrene sphere plombage for
      pulmonary disease caused by multidrug-resistant mycobacteria. Four patients were
      infected with multidrug-resistant strains of Mycobacterium tuberculosis, two with
      Mycobacterium xenopi, one with Mycobacterium avium. All patients were heavily
      pretreated before surgery, had extensive, bilateral cavitary disease and were
      considered unsuitable for resection because of extensive disease or functional
      respiratory impairment. Six patients had active disease at time of surgery.
      Collapse therapy with insertion of six to 18 spheres resulted in long-standing
      bacteriological conversion in six patients. Collapse therapy was unilateral in
      six and bilateral in one. No immediate postoperative complication or death was
      observed. Hospital stay was short (mean 12 d). Collapse therapy is a conservative
      alternative therapy in patients with pulmonary disease caused by multidrug
      resistant mycobacteria at high risk of treatment failure considered unsuitable
      for pulmonary resection.

PMID- 9603146
TI  - Lovastatin induces apoptosis in malignant mesothelioma cells.
AB  - Malignant mesothelioma causes profound morbidity and nearly universal mortality
      that is refractory to conventional treatment with aggressive surgery,
      radiotherapy, or chemotherapy. We report that pharmacologic concentrations of
      lovastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase
      inhibitor, induced apoptosis in human malignant mesothelioma cell lines.
      Mesothelioma cell viability was decreased in a dose-dependent manner by
      lovastatin (5 to 30 microM). These effects were not reversed by exogenous growth
      factors or cholesterol, but were reversed by addition of 100 microM mevalonate,
      confirming that lovastatin affected mesothelioma viability by inhibiting
      mevalonate synthesis. Lovastatin appeared to decrease mesothelioma viability by
      inducing apoptosis, as indicated by morphologic changes, histologic evidence of
      nuclear condensation and degeneration, and flow-cytometric analysis of DNA
      content. Lovastatin's effects on cell viability were partially reversed in the
      presence of farnesol, and treatment of mesothelioma cells with a specific
      farnesyl-protein transferase (FTP) inhibitor decreased cell viability and induced
      morphologic changes indistinguishable from those caused by lovastatin. In
      addition, lovastatin-treated cells showed translocation of ras guanosine
      triphosphate (GTP)-binding proteins from membrane to cytosolic fractions on
      Western blots, suggesting that lovastatin's effects on mesothelioma were mediated
      in part by disrupting acylation of GTP-binding proteins. Thus, lovastatin is a
      commercially available and clinically well-tolerated agent that reduces viability
      and induces apoptosis of mesothelioma cells, and may provide the basis for
      adjunctive treatments of patients with mesothelioma.

PMID- 9603147
TI  - Fixed maximal stroke index in patients after pneumonectomy.
AB  - Patients who have undergone pneumonectomy (PNX) show limited exercise capacity,
      partly attributable to an impaired stroke index (SI). To determine whether this
      limitation is due to deconditioning, we assessed exercise performance and
      cardiopulmonary function in seven patients after PNX (age: 59 +/- 2 yr, mean +/-
      SEM) and eight normal, healthy nonsmokers (52 +/- 3 yr) before and after an
      ergometer exercise training program for 30 min per day, 5 d per week, for 8 wk at
      65% of measured maximal O2 uptake. Lung volume, diffusing capacity of carbon
      dioxide (DL(CO)) and cardiac index (CI) were determined during steady-state
      exercise by a rebreathing method. Exercise endurance was measured at 80% of
      maximal power. As compared with normal subjects, patients who had had PNX showed
      diminished maximal oxygen uptake (VO2max), as well as diminished lung volumes,
      ventilatory capacities, and maximal cardiac and stroke indexes. After training,
      VO2max, endurance, and peripheral O2 extraction improved in both groups. However,
      maximal cardiac and stroke indexes increased only in normal subjects and not in
      patients. We conclude that an irreversibly fixed maximal SI is a major source of
      exercise limitation after PNX, probably because of pulmonary arterial
      hypertension and/or mechanical distortion of the cardiac fossa. Ventilatory
      impairment after PNX did not prevent a training-induced increase in VO2max.
      Exercise training confers significant functional benefit on postpneumonectomy
      patients by enhancing peripheral O2 extraction.

PMID- 9603148
TI  - Early alterations in intracellular and alveolar surfactant of the rat lung in
      response to endotoxin.
AB  - The aim of this study was to characterize early ultrastructural, biochemical, and
      functional alterations of the pulmonary surfactant system induced by Salmonella
      minnesota lipopolysaccharide (LPS) in rat lungs. Experimental groups were: (1)
      control in vitro, 150 min perfusion; (2) LPS in vitro, 150 min perfusion,
      infusion of 50 microg/ml LPS after 40 min; (3) control ex vivo, 10 min perfusion;
      (4) LPS ex vivo, lungs perfused for 10 min from rats treated for 110 min with 20
      mg/kg LPS intraperitoneally. Morphometry of type II pneumocytes showed that LPS
      increased stored surfactant. Lamellar bodies were increased in size, but
      decreased in numerical density, suggesting that giant lamellar bodies observed in
      LPS-treated lungs may result from fusion of normal bodies. Structural analysis of
      alveolar surfactant composition showed that LPS elicited an increase in lamellar
      body-like and multilamellar forms. Bronchoalveolar lavage (BAL) material from LPS
      treated lungs was decreased in phospholipids. BAL bubble surfactometer analysis
      showed a reduction in hysteresis area caused by LPS. We conclude that LPS leads
      to alterations of intracellular and alveolar surfactant within 2 h: fusion of
      lamellar bodies, reduction in surfactant secretion, and changes in alveolar
      surfactant transformation, composition, and function, which may contribute to the
      development of respiratory distress.

PMID- 9603149
TI  - High resolution imaging of the upper respiratory tract with optical coherence
      tomography: a feasibility study.
AB  - A need exists in respiratory medicine for a technology capable of identifying
      airway pathology on a micron scale. This study has demonstrated the feasibility
      of optical coherence tomography (OCT) for ultrahigh resolution imaging of the
      upper respiratory tract by in vitro studies of human tissue. OCT is a relatively
      new technique that can be used to noninvasively collect tomographic images of
      tissue microstructure with micron-scale resolution. OCT is analogous to
      ultrasound, measuring the intensity of infrared light rather than acoustical
      waves. Samples throughout the upper respiratory tract, from the epiglottis to the
      secondary bronchi, were imaged. The resulting images were compared with
      histopathology and verified the ability of OCT to delineate relevant structures
      such as the epithelium, mucosa, cartilage and its sublayers, and glands at a
      resolution higher than any clinical imaging technology. The ability of OCT to
      generate image resolution in the range close to that of histopathology in real
      time, as well as easy integration with small, relatively inexpensive endoscopes,
      low cost, and lack of a need for a transducing medium, supports the hypothesis
      that this optical technology could become a powerful modality in the diagnosis
      and management of a wide range of clinical respiratory pathology.

PMID- 9603150
TI  - Contribution of macrophages to pulmonary nitric oxide production in septic shock.
AB  - Bacterial lipopolysaccharide (LPS) is known to induce the expression of inducible
      nitric oxide synthase (iNOS) in the lung and to lead to increased pulmonary
      nitric oxide (NO) production. The contribution of various pulmonary cells to this
      phenomenon remains unclear. In this study, we used gadolinium chloride, a blocker
      of macrophage activation, to assess the role of macrophages in LPS-induced
      pulmonary NO production. Anesthetized, mechanically ventilated rats were injected
      with either saline or LPS (Escherichia coli endotoxin) and studied for 5 h. Two
      other groups of rats were pretreated 24 h earlier with gadolinium chloride.
      Unlike control rats, rats injected with LPS showed a progressive decline in
      arterial pressure and a several-fold rise in lung iNOS activity and exhaled NO
      concentration. Large numbers of alveolar macrophages also expressed iNOS after
      LPS injection. Gadolinium chloride pretreatment eliminated the rise in lung iNOS
      activity and protein expression and significantly attenuated the increase in
      pulmonary exhaled NO product, but it had no effect on arterial pressure. Fewer
      numbers of alveolar macrophages expressed iNOS protein after gadolinium
      pretreatment. We conclude that macrophage activation plays a critical role in
      enhancing NO production in the respiratory system, but it is of less importance
      in mediating hemodynamic alterations of acute endotoxemia.

PMID- 9603151
TI  - Upregulation of the PDGF-alpha receptor precedes asbestos-induced lung fibrosis
      in rats.
AB  - Platelet-derived growth factor-AA (PDGF-AA) and its matching alpha receptor (PDGF
      R alpha) are upregulated in rat lung fibroblasts (RLFs) after exposure to
      chrysotile asbestos fibers in vitro, which results in asbestos-induced RLF
      proliferation. We now report our in vivo observations, which show an increase in
      the expression of PDGF-R alpha mRNA, but not PDGF-beta receptor mRNA, in asbestos
      exposed rat lungs when compared with RNA from air-exposed (sham) and iron-exposed
      lungs. Western analysis of membrane preparations confirmed the observations on
      mRNA expression by demonstrating an increase in PDGF-R alpha peptide expression
      in the asbestos-exposed rat lungs, compared with that in the air-exposed lungs.
      Immunohistochemistry for the PDGF-R alpha was performed on air- and asbestos
      exposed rat lungs and revealed a clear increase in staining within interstitial
      and subepithelial compartments in the exposed animals. These observations, along
      with our previous report demonstrating an increase in the PDGF-AA isoform
      expression immediately after asbestos-exposure, suggest a scenario in which a
      potent lung mesenchymal cell mitogen, PDGF-AA, and its alpha-receptor are
      upregulated prior to the development of a fibroproliferative lung lesion, and
      thus may play a central role in the pathogenesis of asbestos-induced lung
      fibrosis.

PMID- 9603152
TI  - Airways involvement in rheumatoid arthritis: clinical, functional, and HRCT
      findings.
AB  - The aim of the present study was to assess the prevalence and characteristics of
      airways involvement in rheumatoid arthritis (RA) patients in the absence of
      interstitial lung disease. We prospectively evaluated, with high-resolution
      computed tomography (HRCT) and pulmonary function tests (PFTs), 50 patients with
      RA (nine males and 41 females; mean age: 57.8 yr), including 39 nonsmokers and 11
      smokers (mean cigarette consumption: 15.3 pack-yr) without radiographic evidence
      of RA-related lung changes. PFTs demonstrated airway obstruction (i.e., reduced
      FEV1/VC) in nine patients (18%) and small airways disease (SAD) (i.e., decreased
      FEF(25-75), defined as exceeding the predicted value by 1.64 residual SD [RSD] or
      more, and/or an increased phase III slope > 2 SD by single breath nitrogen
      washout) in four patients (8%). HRCT demonstrated bronchial and/or lung
      abnormalities in 35 cases (70%), consisting of air trapping (n = 16; 32%),
      cylindral bronchiectasis (n = 15; 30%), mild heterogeneity in lung attenuation (n
      = 10; 20%), and/or centrilobular areas of high attenuation (n = 3; 6%). Airway
      obstruction and SAD were correlated with the presence of bronchiectasis and
      bronchial-wall thickening (p = 0.003), and with bronchial infection (p = 0.01),
      but were unrelated to rheumatologic data. FEF(25-75) was reduced and the slope of
      phase III was increased in patients with airway changes on HRCT scans, whereas no
      PFT abnormalities were found in 13 of 15 patients with normal HRCT scans. HRCT
      depicted features of SAD in 20 of the 33 patients with normal PFTs. HRCT findings
      were unrelated to rheumatologic data. A high prevalence of airway abnormalities
      as assessed with HRCT and/or PFTs was observed in our RA population. HRCT appears
      to be more sensitive than PFTs for detecting small airways disease.

PMID- 9603153
TI  - Mechanisms in the pathogenesis of asbestosis and silicosis.

PMID- 9603154
TI  - Pulmonary edema complicating continuous intravenous prostacyclin in pulmonary
      capillary hemangiomatosis.
AB  - Continuous intravenous epoprostenol (prostacyclin) produces hemodynamic and
      symptomatic responses and improves survival in patients with severe primary
      pulmonary hypertension refractory to conventional medical therapy. However, it
      has been recently shown that short-term infusion of epoprostenol can produce
      pulmonary edema in pulmonary veno-occlusive disease, presumably because of
      increased pulmonary perfusion in the presence of downstream vascular obstruction.
      We describe two additional cases of pulmonary edema complicating continuous
      intravenous epoprostenol in patients displaying severe pulmonary hypertension and
      pulmonary capillary hemangiomatosis, a rare condition characterized by the
      proliferation of thin-walled microvessels in the alveolar walls. This report
      indicates that epoprostenol therapy should not be used in patients with severe
      pulmonary hypertension secondary to pulmonary capillary hemangiomatosis.

PMID- 9603155
TI  - Fatal air embolism in an airplane passenger with a giant intrapulmonary
      bronchogenic cyst.
AB  - Considering the large number of airplane passengers with a variety of medical
      conditions, the incidence of in-flight emergencies on commercial airline flights
      is low. Only few cases of pulmonary barotrauma in airplane passengers with prior
      lung pathologies have been reported. We present the unusual case of a female
      airplane passenger with a previously diagnosed asymptomatic giant intrapulmonary
      bronchogenic cyst who experienced fatal air embolism on a commercial airline
      flight. We believe that preventive surgical resection is mandatory in
      asymptomatic patients with large intrapulmonary cysts prior to exposure to even
      small alterations in ambient pressure as, for instance, prior to airplane flight
      or use of mountain cable cars. However, screening for pre-existent lung
      pathologies in the growing mass of commercial airline travelers is not justified.

PMID- 9603156
TI  - Successful pulmonary thromboendarterectomy in two patients with sickle cell
      disease.
AB  - Patients with sickle cell disease have been reported to have an increased risk of
      thromboembolism and pulmonary hypertension. Some of these patients may benefit
      from pulmonary thromboendarterectomy (PTE), a procedure that requires profound
      hypothermia, cardiopulmonary bypass, and periods of circulatory arrest, factors
      that may potentially increase the risk of sickling. Two patients with sickle cell
      disease (sickle-thalassemia [Hb S/beta+] and Hb SS) presented to the Pulmonary
      Vascular Center of UCSD Medical Center with significant shortness of breath and
      limitation of daily activities. Both of these patients were found to have
      surgically accessible chronic thromboembolic disease with pulmonary hypertension.
      PTE was performed in both patients using exchange transfusion, with avoidance of
      anemia, hypoxia, and acidosis. A successful outcome with resolution of pulmonary
      hypertension was achieved in both cases. To our knowledge this is the first
      report of patients with sickle cell disease who successfully underwent PTE for
      chronic thromboembolic pulmonary hypertension.

PMID- 9603157
TI  - Successful treatment with voriconazole of invasive aspergillosis in chronic
      granulomatous disease.
AB  - A 5-year-old boy with chronic granulomatous disease (CGD) was treated with
      amphotericin B for an invasive pulmonary Aspergillus nidulans infection. The
      infection progressed during 6 wk of treatment despite the addition of interferon
      gamma (IFN-gamma), filgrastim, and transfusions with donor granulocytes.
      Treatment with a novel antifungal triazole, voriconazole, resulted in an
      excellent clinical response.

PMID- 9603158
TI  - Effects of esophageal pressure monitoring on sleep architecture.

PMID- 9603159
TI  - Treatment with interleukin-4 prolongs allogeneic neonatal heart graft survival by
      inducing T helper 2 responses.
AB  - BACKGROUND: The T helper (Th) 2 cytokine interleukin (IL)-4 has been implicated
      as a major regulatory cytokine for the induction of transplant tolerance, but few
      studies have examined the capacity of IL-4 to induce tolerance. The effect of IL
      4 therapy alone or with low doses of anti-CD4 monoclonal antibody (mAb) therapy
      on survival of fully allogeneic PVG neonatal heart graft in adult DA rats was
      examined. METHODS: Rat recombinant (r) IL-4 was given at 30 microg (10(4) U)/kg
      daily intraperitoneally for 10 days and MRC OX35 (anti-CD4, nondepleting) or MRC
      OX81 (anti-IL-4) was given intraperitoneally on days 0, 3, 7, and 10.
      Semiquantitative reverse transcriptase-polymerase chain reaction was used to
      assay mRNA for cytokine in the graft, regional node and spleen and fluorescence
      activated cell sorting was used to assay alloantibody Ig isotypes. RESULTS:
      Grafts in rIL-4-treated rats survived a median period of 39 days (range, 28-52
      days), significantly longer than in both untreated and nontransfected Chinese
      hamster ovary-K1 supernatant-treated controls (median, 14 days; range, 10-16
      days, P=0.009). rIL-4 treatment with a suboptimal dose of anti-CD4 mAb prolonged
      median survival to 70 days (range, 63-80 days), which was longer than rIL-4
      treatment alone or anti-CD4 mAb alone (median, 36 days; range, 30-55 days;
      P<0.0045). Combining MRC OX81 with MRC OX35 therapy led to earlier rejection at a
      median period of 26 days (range, 20-28 days); MRC OX81 alone had no effect on
      graft survival. Alloantibody titers, especially IgG1, were higher in rIL-4
      treated animals and lower in anti-CD4 mAb-treated animals than in animals with
      normal rejection (P<0.05). IL-4 mRNA was increased in regional lymph nodes and
      spleen of the rIL-4-treated groups compared with all other groups, but there were
      no differences for IL-2, interferon-gamma, or IL-10. CONCLUSIONS: rIL-4 therapy
      markedly prolonged neonatal cardiac allograft survival, and, with anti-CD4
      therapy, it further prolonged survival. It induced IL-4 mRNA in lymphoid tissues
      and enhanced alloantibody production, especially IgG1, which demonstrated
      enhanced Th2 responses, but did not affect Th1 cytokines.

PMID- 9603160
TI  - The cellular basis of cardiac allograft rejection: VIII. Mechanisms underlying
      delayed allograft rejection in PVG C6-deficient rats.
AB  - BACKGROUND: The delayed allograft rejection in C6-deficient PVG C6- rats compared
      with normal PVG rats has been attributed to the lack of alloantibody activation
      of the membrane attack complex of complement. As T cells alone have been shown to
      effect graft rejection, we examined T-cell responses in PVG C6- rats. METHODS:
      The cellular infiltrate and its mRNA for cytokines and effector molecules in DA
      heart allografts to PVG and PVG C6- rats was compared by immunoperoxidase
      staining and semiquantitative reverse transcriptase polymerase chain reaction.
      The ability of pure populations of T cells or alloantibody to mediate DA heart
      graft rejection in irradiated (750 rads) PVG and PVG C6- rats was also compared.
      RESULTS: The median rejection time of DA heart allografts was 8 days in PVG rats
      and 17.5 days in PVG C6-. PVG C6- rats sensitized to DA by two skin grafts
      rejected DA heart grafts in 5-6 days. CD3+, CD4+, CD8+, interleukin-2 receptor
      positive T cell, macrophage, and natural killer cell infiltration, as well as
      class II major histocompatibility complex and intercellular adhesion molecule-1
      up-regulation, in grafts was similar in naive PVG and PVG C6- rats. mRNA for T
      helper 1 cytokine interleukin-2, interferon-gamma, tumor necrosis factor-beta,
      macrophage molecules tumor necrosis factor-alpha, and inducible nitric oxide
      synthase, as well as cytotoxic T-cell effector molecules perforin and granzyme A
      and B, were found to be the same in the grafts from both naive PVG and naive PVG
      C6- rats. Thus, there appeared to be no difference in the T-cell effector
      response between the PVG and PVG C6- groups. There were higher alloantibody
      titers in PVG C6- rats than in PVG hosts. Irradiation ablated rejection and
      alloantibody responses and reconstitution with naive T cells alone restored
      rejection in both PVG and PVG C6- rats. Irradiated rats given serum from PVG rats
      that had rejected DA grafts did not effect rejection of DA grafts even if given
      naive T cells. Sensitized T cells restored second set. CONCLUSIONS: PVG C6- rats
      have normal T-cell responses and can mediate allograft rejection in the absence
      of alloantibody. The failure of PVG C6- to reject allografts rapidly may be a
      result of the poor clearance of alloantisera leading to enhancement of graft
      survival rather than a critical role for complement and membrane attack complex
      in acute rejection.

PMID- 9603161
TI  - Peritransplant tolerance induction with anti-CD3-immunotoxin: a matter of
      proinflammatory cytokine control.
AB  - BACKGROUND: Tolerance is gaining momentum as an approach to reduce lifelong
      immunosuppressive therapy while improving transplant longevity. Anti-CD3
      immunotoxin (IT), FN18-CRM9, has potential to induce tolerance owing to its
      exceptional ability to deplete sessile lymph node T cells. However, if initiated
      at the time of transplantation, alpha-CD3-IT alone elicits a proinflammatory
      cytokine response, precluding establishment of tolerance. METHODS: Four groups of
      rhesus monkeys received kidney allografts and immunosuppression. Three groups
      received alpha-CD3-IT alone or alpha-CD3-IT supplemented with 15-deoxyspergualin
      (DSG) and/or methylprednisolone (MP). One group received alpha-CD3-monoclonal
      antibody with DSG and MP. Cytokines were measured by enzyme-linked immunosorbent
      assay. RESULTS: Supplementing peritransplant alpha-CD3-IT treatment with a brief
      course of DSG and MP promoted rejection-free kidney allograft acceptance in 75%
      of macaques followed for up to 550 days. Among those given alpha-CD3-IT alone or
      with MP, none were long-term survivors. Tolerance developed after alpha-CD3-IT,
      DSG, and MP treatment, but not when the unconjugated a-CD3 monoclonal antibody
      was substituted for IT. Systemic production of proinflammatory cytokines
      interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha induced after
      peritransplant alpha-CD3-IT was prevented only in animals given DSG. Despite high
      levels of interleukin (IL)-12 in the first month after transplant, tolerant
      recipients exhibited IL-12 resistance, as evidenced by baseline plasma levels of
      IFN-gamma but elevated IL-4. DSG was shown to inhibit IL-12-driven IFN-gamma
      production by a mechanism associated with inhibition of nuclear factor kappa-B.
      CONCLUSIONS: In this model, peritransplant induction of tolerance is promoted by
      efficient elimination of sessile lymph node T cells and control of the
      proinflammatory IFN-gamma response by a mechanism that appears to involve
      resistance to IL-12.

PMID- 9603162
TI  - Staphylococcus aureus nasal colonization and association with infections in liver
      transplant recipients.
AB  - BACKGROUND: Staphylococcus aureus has emerged as a leading cause of bacterial
      infections after liver transplantation. However, the role of nasal colonization
      in the development of S aureus infections has never been explored in liver
      transplant recipients. The objectives of this study were to determine whether
      nasal carriage of S aureus was a risk factor for S aureus infections in liver
      transplant recipients. METHODS: Over a 2-year period, 30 consecutive liver
      transplant recipients were studied. Beginning when the recipients were transplant
      candidates, nasal cultures were performed at each admission and monthly
      thereafter until discharge or death. RESULTS: Overall, 67% (20/30) of the
      patients were nasal carriers, 70% of the carriers had methicillin-resistant S
      aureus (MRSA), 15% had methicillin-sensitive S aureus, and 15% had both MRSA and
      methicillin-sensitive S aureus. Infections were significantly associated with the
      carrier state; 100% (9/9) of the infected patients were carriers as compared with
      50% (11/21) of the noninfected patients (P=0.01). All infections were a result of
      MRSA, and 56% (5/9) of the infections were bacteremia. Median time to the onset
      of S aureus infections was 16 days after transplant. Pulse field gel
      electrophoresis (with digestion of S aureus with SmaI restriction enzyme) in
      seven infected patients demonstrated that the isolates from the anterior nares
      matched the invasive isolates in all cases. A total of 43% (3/7) of these
      infected patients shared the same restriction pattern. CONCLUSION: MRSA
      colonization of the anterior nares was a significant predictor of MRSA infections
      in liver transplant recipients. Infections occurred only in those colonized with
      MRSA and were a result of the endogenously colonizing S aureus strains in all
      cases.

PMID- 9603163
TI  - An analysis of hepatic retransplantation in children.
AB  - BACKGROUND: The limited supply of organ donors has led some groups to reconsider
      the role of retransplantation. Historically, except for children with
      malignancies, extrahepatic sources of sepsis, or severe irreversible neurologic
      injuries, our institution has offered all children with failing liver grafts the
      option of retransplantation regardless of their current severity of illness. The
      purpose of this study was to examine the outcome of hepatic retransplantation in
      children in an attempt to identify factors predictive of outcome and to assess
      the results of our approach to retransplantation. METHODS: Between October 1984
      and December 1995, 314 children less than 15 years of age underwent a total of
      441 liver transplants. Data were obtained retrospectively by review of hospital
      records. RESULTS: With a mean follow-up period of 5.3+/-2.7 years, the overall
      patient survival rates at 1 and 5 years were 77.1% and 67.1%, respectively.
      Primary allograft survival rates were 65.6% and 56.5%, respectively. Of the 137
      patients who developed failure of their primary allograft, 92 underwent
      retransplantation (29.3% of all primary transplants). Both patient and allograft
      survival rates were significantly decreased after retransplantation (P<0.0001
      versus primary transplants). Univariate and multivariate analysis of
      retransplanted patients revealed only two factors that were statistically related
      to patient and graft survival: age at the time of retransplantation (P<0.02
      univariate and P<0.05 multivariate) and retransplantation with a reduced-size
      allograft (P<0.005 univariate and P<0.05 multivariate). In this series, the
      effect on patient survival of differences in medical condition as reflected by
      United Network for Organ Sharing (UNOS) status approached, but did not achieve,
      significance (P=0.08 for UNOS 1 versus UNOS 2 and 3). UNOS status did not affect
      graft survival. Neither the cause of primary allograft loss or the timing of
      retransplantation relative to the first transplant were related to outcome.
      CONCLUSIONS: These data demonstrate that the failure of primary hepatic
      allografts remains a major problem in pediatric liver transplantation and that
      the overall results of retransplantation were significantly worse than those
      associated with primary transplants. We have identified a group of children who
      experienced a significantly worse outcome after retransplantation. This group
      consisted of children less than 3 years of age retransplanted using reduced-size
      grafts. Based on this finding, we now attempt to avoid retransplanting young
      children with reduced-size grafts. By using this approach, we hope to be able to
      offer children the option of retransplantation with improved results and
      simultaneously minimize the negative impact on patients awaiting primary
      transplants.

PMID- 9603164
TI  - Timing and severity of initial hepatitis C recurrence as predictors of long-term
      liver allograft injury.
AB  - BACKGROUND: The majority of patients infected with hepatitis C virus (HCV)
      undergoing liver transplantation develop evidence of histologic recurrence, and
      multiple mechanisms are likely poised to affect long-term allograft injury. The
      purpose of this analysis was to study the hypothesis that histologic and
      biochemical features at the onset of HCV recurrence predict the long-term
      evolution of allograft hepatitis. METHODS: We studied 34 consecutive liver
      transplant recipients with evidence of histologic HCV recurrence and with a
      minimal histologic follow-up of 1 year (up to 6.2 years; mean: 696+/-83.2 days).
      Two-hundred and seventy-eight serial allograft biopsies (mean: 6.85+/-0.62 per
      patient, range: 4-21) were analyzed. The hepatic activity index was utilized to
      quantitate piecemeal necrosis, intralobular degeneration, portal inflammation,
      and hepatic fibrosis. The presence of hepatocyte ballooning degeneration and
      cholestasis was also assessed. RESULTS: Although there was no significant
      difference with regard to initial hepatic activity index scores between patients
      who ultimately developed allograft cirrhosis (group 1; n=8) versus those with
      milder hepatitis (group 2; n=26), the finding of ballooning
      degeneration/cholestasis was more frequent in the former group (P=0.04). The
      distribution of HCV genotypes, the mean follow-up after orthotopic liver
      transplantation, the mean number of allograft biopsy specimens per patient, basal
      immunosuppression, and incidence of rejection were comparable in both groups.
      Patients who ultimately developed allograft cirrhosis had significantly higher
      initial total bilirubin at the onset of histologic recurrence and peak total
      bilirubin (pT. Bili, the highest value in the ensuing month). Actuarial rates of
      moderate-to-severe allograft hepatitis were significantly greater in patients
      with pT. Bili > or = 3.5 mg/dl (P=0.004). Multiple regression analysis identified
      pT. Bili as the only independent predictor of allograft cirrhosis. CONCLUSIONS:
      Features at the onset of histologic HCV recurrence predict the natural history of
      allograft injury; specifically, marked, transient hyperbilirubinemia is
      associated with the subsequent development of allograft cirrhosis.

PMID- 9603165
TI  - Treatment of posttransplant hypertension by laparoscopic bilateral nephrectomy?
AB  - BACKGROUND: Hypertension is an important risk factor for the development of
      chronic graft failure and decreased graft and patient survival after renal
      transplantation. METHODS: Between September 1994 and August 1996, 14 patients
      underwent laparoscopic bilateral nephrectomy for treatment of drug-resistant
      hypertension after successful renal transplantation. Common causes of
      hypertension were largely excluded before bilateral nephrectomy. A scoring system
      was developed for comparison of different antihypertensive regimes. In this
      system, points were given according to type and dosage of each antihypertensive
      drug. RESULTS: At 6-month follow-up, all patients showed well-controlled blood
      pressure (median of mean arterial pressure: 104 vs. 130 mmHg preoperatively,
      P<0.001, n=14), and significantly fewer antihypertensive drugs were needed
      according to the scoring system (48.9+/-20.9 points vs. 105.9+/-23.5 points
      preoperatively, P<0.001, n=14). During laparoscopy, three conversions to open
      surgery were necessary. Postoperatively, four complications occurred. After
      laparoscopy, immunosuppression and other oral medication were given continuously.
      The hospital stay ranged between 3 and 6 days (median: 5 days). CONCLUSIONS: The
      results indicate that bilateral nephrectomy using the laparoscopic technique can
      be an effective alternative method for a selected group of patients with severe
      hypertension, which is unresponsive to conservative management after successful
      renal transplantation with regard to improving the long-term graft survival.

PMID- 9603166
TI  - Should all human immunodeficiency virus-infected patients with end-stage renal
      disease be excluded from transplantation? The views of U.S. transplant centers.
AB  - BACKGROUND: Human immunodeficiency virus (HIV)-infected patients have generally
      been excluded from transplantation. Recent advances in the management and
      prognosis of these patients suggest that this policy should be reevaluated.
      METHODS: To explore the current views of U.S. transplant centers toward
      transplanting asymptomatic HIV-infected patients with end-stage renal disease, a
      written survey was mailed to the directors of transplantation at all 248 renal
      transplant centers in the United States. RESULTS: All 148 responding centers said
      they require HIV testing of prospective kidney recipients, and 84% of these
      centers would not transplant an individual who refuses HIV testing. The vast
      majority of responding centers would not transplant a kidney from a cadaveric
      (88%) or a living donor (91%) into an asymptomatic HIV-infected patient who is
      otherwise a good candidate for transplantation. Among the few centers that would
      consider transplanting an HIV-infected patient, not a single center had performed
      such a transplant in the year prior to the survey. Most centers fear that
      transplantation in the face of HIV infection would be harmful to the individual,
      and some believe that it would be a waste of precious organs. CONCLUSIONS: The
      great majority of U.S. renal transplant centers will not transplant kidneys to
      HIV-infected patients with end-stage renal disease, even if their infection is
      asymptomatic. However, advances in the management of HIV infection and a review
      of relevant ethical issues suggest that this approach should be reconsidered.

PMID- 9603167
TI  - De novo collapsing glomerulopathy in renal allografts.
AB  - BACKGROUND: Collapsing glomerulopathy is a recently described form of glomerular
      injury characterized by capillary collapse and visceral epithelial
      hypercellularity associated with nephrotic range proteinuria and a rapid,
      progressive decline in renal function. The lesion has rarely been described in
      allografts. METHODS: We reviewed 892 allograft biopsies from a population of 1079
      recipients who received renal transplants between 1978 and 1996. RESULTS: Five
      cases of de novo collapsing glomerulopathy were identified (0.6% of biopsies;
      3.2% since 1993). None occurred before 1993. The patients were 31 to 66 years of
      age and they presented 6 to 25 months after transplantation. The 24-hr urinary
      protein ranged from 1.8 to 11.8 g. All patients and donors were negative for the
      human immunodeficiency virus and had no risk factors for human immunodeficiency
      virus infection. Diffuse or focal, global or segmental collapse of glomerular
      capillaries, swelling and hypercellularity of the visceral epithelium, hyaline
      arteriolosclerosis, and interstitial fibrosis were characteristic histologic
      features. Two cases had concomitant glomerular immune complex deposits.
      Progressive decline in allograft function occurred within 2-24 months after
      diagnosis, culminating in return to dialysis in all patients. CONCLUSION:
      Collapsing glomerulopathy can arise in renal allografts as a de novo disease.
      Although its pathogenesis remains to be clarified, it is important to distinguish
      this lesion in allografts as it can be associated with rapidly progressive graft
      failure.

PMID- 9603168
TI  - A new enzyme-linked immunosorbent assay to measure anti-endothelial antibodies
      after cardiac transplantation demonstrates greater inhibition of antibody
      formation by tacrolimus compared with cyclosporine.
AB  - BACKGROUND: Chronic rejection or transplant-associated coronary artery disease
      (TxCAD) is the most serious complication after human cardiac transplantation.
      Previous studies, using Western blotting, have shown formation of antibodies
      against endothelial antigens of 56 and 58 kDa, which are associated with early
      TxCAD. These antigens were later identified as being vimentin and its breakdown
      products. The aims of the present study were to devise a robust assay for
      detection of anti-vimentin antibodies and to compare antibody formation in
      patients taking different immunosuppressive drugs. METHODS: 106 sequential serum
      samples from 19 patients taking tacrolimus and 68 sera from 12 patients taking
      cyclosporine were examined by enzyme-linked immunosorbent assay (ELISA) for anti
      vimentin antibodies and Western blotting for reactivity against bands at 56/58
      kDa. Serum samples were taken before transplantation and at 1, 3, 6, 9, and 12
      months. RESULTS: The vimentin ELISA produced significantly higher numbers of
      positive episodes per patient (3.92+/-1.08) compared with use of Western blotting
      (2.54+/-0.52). Serum from patients taking tacrolimus contained significantly less
      antibodies measured by ELISA (15.8%) or Western blotting (6.5%) than sera from
      patients taking cyclosporine (46.8% for ELISA; P=0.001 and 21% by Western
      blotting, P=0.01). Intravascular ultrasound performed on six patients at 12
      months showed a correlation between anti-vimentin antibody formation and
      detection of early coronary disease. CONCLUSIONS: The results demonstrate first,
      that differences in antibody profiles produced by different immunosuppressive
      drugs, and second, that detection of anti-vimentin antibodies may be a
      noninvasive method of detecting disease activity in transplanted vessels.

PMID- 9603169
TI  - Gender-related assessment of cyclosporine/prednisolone/sirolimus interactions in
      three human lymphocyte proliferation assays.
AB  - BACKGROUND: Cyclosporine (CsA), prednisolone (Pred), and sirolimus (Sir) are
      immunosuppressive compounds inhibiting lymphocyte proliferation at the cytokine
      gene transcription (CsA and Pred) or signal transduction (Sir) levels. METHODS:
      Double- and triple-drug interactions were simultaneously studied using lectin
      induced proliferation of isolated cell lymphocytes (ICLP) and whole blood
      lymphocytes from men and women as well as two-way mixed lymphocyte reaction
      assays. Drug interactions were described with isobolograms and quantitated with
      the universal response surface approach by estimating the interaction parameter
      alpha. RESULTS: All compounds inhibited more than 89% of control proliferative
      responses. In each assay, CsA was less potent than Pred (3- to 14-fold) and Sir
      (5- to 11-fold). Sir was of similar or higher potency than Pred and 1.5-fold more
      potent in men than women. Pred was 1.4 times more potent in women but this was
      found only in the ICLP assay. All combinations were synergistic (alpha>0), with
      greater synergism found for combinations involving Sir, especially in the ICLP
      (alpha>13) and two-way mixed lymphocyte reaction (alpha>40) assays. Moreover, the
      Sir/Pred interaction in the ICLP assay was two to five times more synergistic in
      women, because their mean alpha was 56 compared with 13 in men. Double
      combination alpha values were able to reasonably describe CsA/Pred/Sir triple
      interaction effects. CONCLUSIONS: These studies indicate that CsA, Pred, and Sir
      act and synergistically interact in vitro, with gender and assay as additional
      factors, and that whole blood lymphocyte proliferation cultures are useful in
      assessing the nature and intensity of drug interactions.

PMID- 9603170
TI  - Transient complement inhibition plus T-cell immunosuppression induces long-term
      survival of mouse-to-rat cardiac xenografts.
AB  - BACKGROUND: The use of anti-B-cell and T-cell immunosuppressive agents leads to
      only a few weeks' survival of mouse-to-rat cardiac xenografts. METHODS: BALB/c
      cardiac xenografts were transplanted to Lewis rats treated with cyclosporine
      (CsA) and/or cobra venom factor (CVF). RESULTS: CsA alone did not prolong
      xenograft survival (2.2+/-0.4 days), whereas CVF alone led to minimal
      prolongation of survival (5.6+/-0.8 days) as compared with nontreated recipients
      (2.4+/-0.5 days). The combination of CsA plus CVF, the latter given for either 2
      days or 11 days, resulted in long-term survival of 14/16 hearts (> 100 days).
      Production of IgM elicited xenoreactive antibodies (EXA) peaked on day 4 after
      transplantation and decreased thereafter. Production of IgG EXA occurred only in
      the control group, whereas, in the CsA/CVF-treated group, IgG EXA were totally
      suppressed. Long-term surviving grafts showed (i) excellent preservation of
      morphology and minimal leukocyte infiltration, (ii) deposition of IgM, IgG and
      weak C3 deposition on the graft endothelium, (iii) low level infiltration by rat
      macrophages, (iv) replacement of mouse dendritic cells by class II+ rat
      macrophages, and (v) expression within endothelial and smooth muscle cells,
      macrophages, and myocytes of HO-1, a "protective gene" not seen in the rejected
      hearts. CONCLUSIONS: Our present findings suggest that long-term mouse-to-rat
      cardiac xenograft survival is induced by temporary suppression of C activation
      and sustained T-cell suppression leading to inhibition of IgG EXA production.
      Florid expression of a protective gene (HO-1) may contribute to survival.

PMID- 9603171
TI  - Role of intrathymic rat class II+ cells in maintaining deletional tolerance in
      xenogeneic rat-->mouse bone marrow chimeras.
AB  - BACKGROUND: Mixed xenogeneic bone marrow chimerism and tolerance can be induced
      in mice conditioned with a nonmyeloablative regimen followed by injection of T
      cell-depleted rat bone marrow cells. We hypothesized that, despite a gradual
      decline in rat hematopoiesis observed in these chimeras, as long as rat class II+
      antigen-presenting cells remain in their thymi, tolerance will persist as a
      result of deletion of donor-reactive thymocytes. METHODS: The level of chimerism
      and of mouse Vbeta5 and Vbeta11 T-cell deletion was followed over time. These
      results were correlated with the presence of rat class II+ cells in the thymus by
      immunohistochemistry and the presence of tolerance in long-term chimeras by in
      vivo and in vitro assays. RESULTS: (1) Proliferation and cytotoxicity assays, as
      well as skin graft survival, demonstrated the presence of specific tolerance to
      host and to donor rat, with normal reactivity to third-party rat and mouse
      stimulators, even as late as 85 weeks after bone marrow transplantation. (2) The
      absence of mature Vbeta5+ and Vbeta11+ host T cells in the thymus and periphery
      was always associated with the presence of rat class II+ cells in the thymus, and
      incomplete deletion of T cells expressing these Vbeta families was observed in
      thymi in which rat class II+ cells were not detectable. CONCLUSIONS: Donor
      specific T-cell tolerance is maintained during the period when donor-type
      reconstitution declines, and is most likely mediated by intrathymic clonal
      deletion of T cells that recognize antigens expressed on class II+ rat cells.

PMID- 9603172
TI  - Prevention of autoimmune destruction of syngeneic islet grafts in spontaneously
      diabetic nonobese diabetic mice by a combination of a vitamin D3 analog and
      cyclosporine.
AB  - BACKGROUND: Type 1 diabetes is characterized by the presence of an autoimmune
      memory, responsible for the destruction of even syngeneic islet grafts. This
      recurrence of autoimmunity is partly responsible for the need of extensive
      immunosuppression in pancreas and islet transplantation in type 1 diabetic
      patients. The aim of the study was to evaluate the capacity of a 20-epi-analog of
      vitamin D3, KH1060, both alone and in combination with cyclosporine (CsA) to
      prevent diabetes recurrence in syngeneic islet grafts in nonobese diabetic (NOD)
      mice. METHODS: Spontaneously diabetic NOD mice grafted with syngeneic islets
      (n=500) under the kidney capsule were treated with KH1060, CsA, or a combination
      of both drugs from the day before transplantation until recurrence or 60 days
      after transplantation. RESULTS: Vehicle-treated mice showed a recurrence of
      diabetes in 100% of cases (n=17) within 4 weeks. Treatment with high doses of CsA
      (15 mg/kg/day) or KH1060 (1 microg/kg/2 days) significantly prolonged islet
      survival (60 days and 50 days, respectively, versus 9.5 days in controls; P<0.001
      and P<0.0001). Mice treated with subtherapeutical doses of both drugs combined
      (KH1060 0.5 microg/kg/2 days + CsA 7.5 mg/kg/day) had significant prolongation of
      graft survival (48 days; P<0.001) and more importantly, four of five mice that
      were still normoglycemic 60 days after transplantation showed no recurrence after
      discontinuation of all treatment. Histology of the grafts of control and
      combination-treated mice demonstrated that graft infiltration and islet
      destruction were less severe in grafts of combination-treated mice. Cytokine mRNA
      analysis in the grafts 6 days after transplantation revealed a clear suppression
      of interleukin-12 and T helper 1 cytokines and higher levels of interleukin-4 in
      combination-treated mice. CONCLUSIONS: KH1060, an analog of 1,25(OH)2D3, delays
      autoimmune disease recurrence after syngeneic islet transplantation in NOD mice,
      both alone and especially in combination with CsA, possibly restoring tolerance
      to beta cells in 30% of cases.

PMID- 9603173
TI  - Long-term expression of the gene encoding green fluorescent protein in murine
      hematopoietic cells using retroviral gene transfer.
AB  - BACKGROUND: A major goal in retroviral-based gene therapy is to establish methods
      that allow for selection and tracking of transduced cell populations. Green
      fluorescent protein (GFP) may be useful for gene therapy applications because it
      is a naturally fluorescent protein that can be detected using conventional flow
      cytometers facilitating rapid analysis and purification of transduced cell
      populations. However, it is unknown whether GFP can be stably expressed in vivo,
      particularly in multiple bone marrow-derived cell lineages. METHODS: A murine
      retrovirus carrying the gene encoding GFP was used to infect murine bone marrow
      cells (BMCs). These studies were conducted to (1) directly determine whether GFP
      could be used as a marker of BMC transduction, (2) determine whether GFP is
      capable of being expressed in multiple bone marrow-derived hematopoietic cell
      lineages, and (3) determine whether GFP could be used to follow the fate of
      transduced cells in vivo. RESULTS: Infection of BMCs with retroviruses carrying
      the gene encoding GFP resulted in a fluorescent signal in viable transduced cells
      that was detectable by flow cytometry. Expression of GFP was detected in multiple
      bone marrow-derived cell lineages after transduction, including stem cell antigen
      positive (Sca-1+), lineage marker-negative (Lin-) cells. Using GFP as a
      selectable marker, we were able to enrich for transduced cells by cell sorting.
      Mice reconstituted with enriched populations of GFP+ cells showed a significant
      increase in the percentage of cells expressing GFP in the periphery when compared
      with mice reconstituted with unenriched transduced bone marrow. CONCLUSIONS:
      These data indicate that GFP can be used to select for transduced BMCs in vitro,
      expressed in multiple bone marrow-derived cell lineages, used to select
      transduced cells, and follow the fate of transduced cells long-term in vivo.

PMID- 9603174
TI  - CD30 expression identifies a functional alloreactive human T-lymphocyte subset.
AB  - BACKGROUND: CD30 is a member of the tumor necrosis factor/nerve growth factor
      receptor family and has been proposed as a marker of specific cytokine-producing
      subsets in humans. Previous studies have examined the expression of CD30 on
      established T helper type 1 and T helper type 2 cell clones and the function of
      CD30+ cells after mitogenic stimulation. In this study, we examined the
      development and function of CD30+ T cells generated in response to alloantigen.
      METHODS: Primary one-way mixed lymphocyte reactions were established, and the
      expression of CD30 on T lymphocytes was determined by immunofluorescence and flow
      cytometry. Fluorescence-activated cell sorting was utilized to define the
      cytokine profile of alloactivated CD30+ cells after restimulation with anti-CD3
      monoclonal antibodies or alloantigen. The effect of cyclosporine on the
      development of CD30+ cells, and on cytokines produced by CD30+ T lymphocytes, in
      response to alloantigen was determined. RESULTS: CD30+ T lymphocytes could be
      detected on day 2 of mixed lymphocyte reactions and continued to increase in
      number and proportion through day 6. Both CD4 and CD8 T cells expressed CD30
      after primary alloantigenic stimulation. CD30+ T cells are a subset of
      alloactivated T cells and are the major source of interferon-gamma and
      interleukin-5 produced in response to alloantigen. Cyclosporine partially, but
      not completely, inhibits the development of CD30+ cells, and has a greater effect
      on interferon-gamma production than on interleukin-5 production. CONCLUSIONS:
      CD30+ T lymphocytes may constitute an important immunoregulatory subset in human
      allograft rejection.

PMID- 9603175
TI  - Effect of cyclosporine and tacrolimus on the growth of Epstein-Barr virus
      transformed B-cell lines.
AB  - BACKGROUND: Transplant patients receiving immunosuppressive drugs are at
      increased risk for Epstein-Barr virus (EBV)-associated disorders including
      posttransplant lymphoproliferative disorder. The function of T lymphocytes, which
      are critical to preventing the expansion of EBV-infected B cells, is inhibited by
      immunosuppressive drugs. The purpose of this study was to determine whether
      immunosuppressive drugs have direct effects on EBV-infected B cells. METHODS: The
      growth and proliferation of EBV-infected spontaneous lymphoblastoid cell lines
      (SLCLs), cultured in the presence or absence of cyclosporine (CsA) and tacrolimus
      (TAC), were measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide and [3H]thymidine incorporation assays. The effect of CsA and TAC on the
      viability of SLCLs was determined by cell counts with trypan blue. Apoptosis of
      SLCLs was induced with an anti-Fas agonist monoclonal antibody in the presence or
      absence of CsA and TAC and measured by flow cytometry after terminal
      deoxynucleotidyl transferase end-labeling and propidium iodide staining. RESULTS:
      CsA and TAC, but not sirolimus, increased the growth of SLCLs. The increased
      growth in the presence of CsA and TAC was attributable to enhanced cell viability
      and not increased cell division of SLCLs. In addition, CsA and TAC inhibited Fas
      mediated apoptosis of SLCLs. CONCLUSIONS: CsA and TAC enhance the survival of EBV
      transformed B-cell lines. CsA and TAC promote or augment SLCL growth through
      protection from cell death but do not affect cell division. The inhibition of
      cell death by CsA and TAC may contribute to the expansion of EBV-infected cells
      in immunosuppressed individuals.

PMID- 9603176
TI  - T-cell and monocyte subsets, inflammatory molecules, rejection, and hemodynamics
      early after cardiac transplantation.
AB  - BACKGROUND: In the early period after cardiac transplantation, differential
      diagnosis of graft failure due to rejection, infection, and other causes is
      important but difficult. METHODS: In 22 consecutive patients undergoing heart
      transplantation, we prospectively determined levels of interleukin-6 as well as T
      cell and monocyte subsets at eight points in time during biopsy and right heart
      catheterization and within 12 hr of echocardiography during the first 3 months
      after transplantation. RESULTS: Worse hemodynamic parameters, as characterized by
      dichotomization according to median values (pulmonary capillary wedge pressure
      >10 mmHg, mean pulmonary arterial pressure > 18 mmHg, pulmonary vascular
      resistance > 115 dyn x sec x cm(-5), right atrial pressure > 5 mmHg, cardiac
      index <3 L/min/m2, early mitral deceleration time < 135 msec, and isovolumic
      relaxation time <80 msec), were associated with higher levels of interleukin-6, C
      reactive protein, polymorphonuclear cells, CD71+/CD14+ monocytes, and IgM levels
      and, in contrast, with lower levels of immunocompetence markers such as CD3+ T
      cells, CD4+ T cells, CD8+ T cells, CD3+/CD25+ T cells, CD4+/ CD45RO+ T cells, NK
      cells, and lower biopsy scores. CONCLUSION: Early after cardiac transplantation,
      elevated levels of inflammatory cells and soluble inflammatory molecules and
      lower levels of immunocompetence markers are associated with impaired allograft
      function in the absence of cellular rejection.

PMID- 9603177
TI  - Successful transplantation of porcine livers after warm ischemic insult in situ
      and cold preservation including postconditioning with gaseous oxygen.
AB  - BACKGROUND: In order to reduce the shortage of viable donor livers for organ
      transplantation, a method has been developed that allows even predamaged livers
      from nonheartbeating donors to be used as transplantable organs. METHODS: Porcine
      livers were harvested 45 min after cardiac arrest of the nonheparinized donor,
      preflushed with heparinized saline solution, and subsequently rinsed with
      University of Wisconsin solution, to which superoxide dismutase was added as an
      oxygen free radical scavenger. Thereafter, the livers were persufflated with
      gaseous oxygen via the venous vascular system while immersed in University of
      Wisconsin solution at 4 degrees C for 4 to 5 hr. RESULTS: After orthotopic
      transplantation, all of the livers conditioned with gaseous oxygen were able to
      support life-sustaining function during the whole observation period of 7 days
      post transplantation, while no survival of the recipients could be obtained
      without the described treatment. CONCLUSIONS: The present study establishes a new
      perspective for the use of ischemically altered livers from nonheartbeating
      donors for organ transplantation under clinical circumstances.

PMID- 9603178
TI  - Reconstruction of an abnormal hepatic vein in a donor liver: a case report.
AB  - In the era of worldwide organ shortage for liver transplantation, every effort
      must be made to use all potentially available livers. In this case report, we
      present a liver graft with abnormal left hepatic vein draining directly to the
      right atrium of the donor heart, which was discovered during back table
      preparation of a liver graft. The vein was reconstructed and the subsequent liver
      transplantation was successful. Five years after the transplantation, no signs of
      complications have emerged.

PMID- 9603179
TI  - Four cases of human herpesvirus 6 variant B infection after pediatric liver
      transplantation.
AB  - BACKGROUND: Little is known about human herpesvirus (HHV)-6 infection after liver
      transplantation. We present our experiences with four cases of HHV-6 infection
      after liver transplantation from living related donors. METHODS: Peripheral blood
      was collected from four donor and recipient pairs at the time of transplantation
      and biweekly from the recipients after transplantation. We attempted to isolate
      HHV-6 and measure antibody titers to HHV-6 and HHV-7. RESULTS: HHV-6 was isolated
      from four recipients approximately 2 weeks after transplantation. A significant
      rise in HHV-6 antibody titers was observed in four recipients at some point in
      their course, whereas HHV-7 antibody titers were increased in one recipient. Four
      isolates were variant B. When HHV-6 was isolated, all recipients had an
      unexplained fever. CONCLUSIONS: HHV-6 variant B infection after pediatric liver
      transplantation was confirmed. HHV-6 infection occurred approximately 2 weeks
      after transplantation. Moreover, there appears to be an association between HHV-6
      infection and unexplained fever.

PMID- 9603180
TI  - CD4 lymphocytopenia as a risk factor for skin cancers in renal transplant
      recipients.
AB  - BACKGROUND: Renal transplant recipients are at increased risk of developing skin
      cancer. It remains difficult to establish the actual influence of
      overimmunosuppression in the development of skin cancers. We investigated whether
      lymphocyte subset count may predict the risk of developing skin cancer in long
      term renal transplant recipients. METHODS: One hundred fifty long-term renal
      transplant recipients were followed for a mean period of 26 months. Each patient
      was examined at least annually by a dermatologist. Lymphocyte subsets were
      measured annually. RESULTS: Fifteen patients exhibited skin cancers. Patients
      with and without skin cancer did not differ in age, gender, transplant duration,
      hemodialysis duration before transplantation, immunosuppressive regimen, and
      serum creatinine concentration. CD4 cell counts were significantly lower in
      patients with skin cancers (330+/-179/mm3 vs. 503+/-338/mm3; P<0.01), whereas
      total lymphocyte and CD8 and CD19 cell counts were similar between the two
      groups. CONCLUSIONS: CD4 cell depletion is associated with skin cancer in long
      term renal transplant recipients.

PMID- 9603181
TI  - Hyperlipidemia in renal transplant recipients treated with sirolimus (rapamycin).
AB  - BACKGROUND: Sirolimus is an interesting immunosuppressive drug that does not seem
      to cause nephrotoxicity, neurotoxicity, or diabetogenicity, as commonly seen in
      patients treated with cyclosporine or tacrolimus. In this report, we describe a
      possible association between sirolimus and observed hyperlipidemia. METHODS:
      Serum levels of triglycerides and cholesterol were analyzed in 11 patients who
      participated in a pilot study evaluating the effect of oral sirolimus or placebo
      combined with cyclosporine and corticosteroids on the occurrence of acute renal
      transplant rejection. RESULTS: In four of nine patients given sirolimus,
      significantly increased serum triglyceride levels were seen, with peak levels
      occurring 2-4 months after transplantation and ranging between 11.7 and 42.0
      mmol/L (reference value <2.2 mmol/L). In two patients given placebo, the serum
      triglyceride levels remained below 5.0 mmol/L. After reduction or discontinuation
      of sirolimus, the serum triglyceride levels decreased within 1-2 months and after
      1-8 months levels had returned to their pretransplant values. A significant
      increase in serum cholesterol levels was seen in one of nine patients given
      sirolimus. CONCLUSION: It seems that long-term treatment with sirolimus in
      combination with cyclosporine and corticosteroids may increase the risk of
      hypertriglyceridemia.

PMID- 9603182
TI  - Preservation of immunological and colony-forming capacities of long-term (15
      years) cryopreserved cord blood cells.
AB  - BACKGROUND: Cryopreserved cord blood may be stored for decades before being used
      for allogeneic stem cell transplantation. Little is known about the effect of
      long-term cryopreservation in liquid nitrogen on the viability and function of
      cord blood cells. We examined the recovery, viability, clonogenic capacity, and T
      cell reactivity to HLA alloantigens of cord blood samples cryopreserved up to 15
      years. METHODS: Progenitor cell recoveries were studied by (colony-forming unit
      granulocyte-macrophage) clonogenic assays from 18 cord blood samples short-term
      frozen for 2-8 weeks and from 8 samples cryopreserved for 15 years. Proliferative
      and cytotoxic responses against HLA antigens of thawed cord blood mononuclear
      cells after short-term or long-term cryopreservation were tested in standard
      mixed lymphocyte cultures and cell-mediated lympholysis assays. RESULTS: After
      thawing, the mononuclear cell recovery from long-term frozen cord blood low
      density fractions averaged 80% (range, 64% to 92%). The presented data show that
      long-term frozen cord blood cells keep their clonogenic potential. No damaging
      effect was seen on the proliferative and cytotoxic capacities of long-term frozen
      cord blood T cells. CONCLUSIONS: The results support the possibility of long-term
      storage of progenitor cells from umbilical cord blood for future bone marrow
      reconstitution.

PMID- 9603183
TI  - Xenospecific CD8+ cytotoxic T lymphocyte generation: accessory function for CD4+
      T cells and natural killer 1.1+ cells.
AB  - BACKGROUND: Controversy exists as to whether natural killer (NK)1.1+ cells
      additionally support cytotoxic T lymphocyte (CTL) generation. We have previously
      demonstrated that mice generate a strong in vitro xenospecific CTL response in
      local popliteal lymph nodes (LN) to footpad immunizations with large numbers of
      human tumor cells. METHODS: In vivo depletion of various LN subsets using
      cytotoxic monoclonal antibodies was used to determine their relative importance
      in stimulating xenospecific CD8+ CTL responses to human Jurkat tumor cells.
      Depletion of functional NK cells in vivo was evidenced by the relative lack of
      NK1.1+ cells and NK activity in the spleens and LN of anti-NK1.1 monoclonal
      antibody-treated mice. CONCLUSION: Depletion of LN subsets indicated that CD4+ T
      cells were critical in generating an effective xenospecific CD8+ CTL response,
      but also suggested that NK1.1+ cells play a significant additional accessory role
      in the development of mouse anti-human xenospecific CTL.

PMID- 9603184
TI  - Commentary on ciprofloxacin-dependent superinduction of interleukin-2 synthesis
      and thymidine uptake.

PMID- 9603185
TI  - Treatment of graft-versus-host disease with photopheresis.

PMID- 9603186
TI  - Alopecia as a consequence of tacrolimus therapy.

PMID- 9603187
TI  - The cholinergic gene locus.
AB  - Messenger RNAs and the cognate gene(s) encoding choline acetyltransferase (ChAT)
      and the vesicular acetylcholine transporter (VAChT) have been cloned from mammals
      and several other animal classes in the last decade. These have provided
      molecular tools for investigating acetylcholine synthesis and packaging into
      synaptic vesicles, the genesis of cholinergic vesicles, and the development and
      senescence of the cholinergic nervous system. VAChT and ChAT have been found to
      share a common gene locus and regulatory elements for gene transcription. The
      cholinergic gene locus represents a previously undiscovered type of neuronal
      transcriptional unit controlling chemically coded neurotransmission. In vitro
      assays for the transport function of VAChT have shed light on the bioenergetics
      of amine accumulation in secretory vesicles. Manipulation of VAChT expression in
      vivo has demonstrated unequivocally the primacy of vesicular exocytosis as the
      mode of transmitting quanta of acetylcholine at the neuromuscular junction, as in
      vivo manipulation of acetylcholinesterase levels has demonstrated the importance
      of acetylcholine metabolism in the regulation of complex functions such as
      cognition. Light and electron microscopic visualization of VAChT, complementing
      previous ChAT immunohistochemistry, has improved understanding of the genesis and
      function of the cholinergic vesicle, neuron, and synapse. These advances should
      accelerate the development of "cholinergic" pharmacological and gene therapeutic
      approaches to treatment of human diseases that are associated with cholinergic
      surfeit and insufficiency.

PMID- 9603188
TI  - Cloning and chromosomal mapping of the murine norepinephrine transporter.
AB  - The norepinephrine (NE) transporter (NET), a target of many clinically prescribed
      antidepressants, regulates noradrenergic neurotransmission by efficiently
      clearing NE from synaptic spaces after release. To advance our understanding of
      NET gene structure, regulation, and potential associations with complex
      behavioral trait loci, we amplified a mouse norepinephrine transporter (mNET)
      cDNA from placenta total RNA and utilized mNET probes to isolate and characterize
      the mNET gene. Inferred translation of the major open reading frame of the mNET
      cDNA predicts a 617-amino acid protein with 12 putative membrane-spanning regions
      and 94% identity to human NET. The coding exons of the mNET cDNA were found to be
      spread across >36 kb of 129/Svj genomic DNA, with exon-intron boundaries bearing
      consensus gt/ag splice sites. Sequence upstream (202 bp) of the inferred
      translation initiation site matched the sequence of 5' rapid amplification of
      cDNA ends products from brain mRNA with no evidence for intervening introns and
      is preceded by a TATA box and canonical transcriptional regulatory elements that
      may play a role in mNET expression in vivo. Probes derived from mNET cDNA
      identified species-specific MspI restriction fragment length variations within
      the mNET gene that were utilized to position the gene (Slc6a5) to murine
      chromosome 8, one recombinant distal to D8Mit15. This site is within a recently
      defined quantitative trait locus defined for ethanol sensitivity in LSXSS
      recombinant inbred mice, Lore4. The status of Slc6a5 as a candidate gene for
      alcohol sensitivity is discussed with respect to studies noting ethanol-induced
      alterations in brain NE receptors, NE receptor-linked adenylate cyclase, and NE
      transport.

PMID- 9603189
TI  - Cloning, expression, and pharmacology of four human 5-hydroxytryptamine 4
      receptor isoforms produced by alternative splicing in the carboxyl terminus.
AB  - We report here the molecular cloning of three new splice variants of the human
      serotonin 5-hydroxytryptamine4 (h5-HT4) receptor, which we named h5-HT4(b), h5
      HT4(c), and h5-HT4(d). The sequence following the splicing site at Leu358 in the
      C-terminal tail of h5-HT4(b) displays a 74% protein identity with the same region
      in the long form of the rat 5-HT4 receptor (r5-HT4L) but is shorter by 18 amino
      acids compared to its rat counterpart. The splice variants h5-HT4(c) and h5
      HT4(d) are the first of their kind to be described in any animal species. The C
      terminus of h5-HT4(c) displays a high number of putative phosphorylation sites.
      The h5-HT4(d) isoform corresponds to an ultrashort form of the receptor, with a
      truncation two amino acids after the splicing site. Tissue distribution studies
      revealed some degree of specificity in the pattern of expression of the different
      isoforms within the human body. The four splice variants transiently expressed in
      COS-7 cells displayed an identical 5-HT4 pharmacological profile and showed a
      similar ability to stimulate adenylyl cyclase activity in the presence of 5-HT.
      The stimulatory pattern of cyclic AMP formation in response to the 5-HT4 agonist
      renzapride was found to be significantly different between h5-HT4(a) and the
      other h5-HT4 isoforms, indicating that the splice variants may differ in the way
      they trigger the signal transduction cascade following receptor activation.

PMID- 9603190
TI  - Functional analysis of a voltage-gated sodium channel and its splice variant from
      rat dorsal root ganglia.
AB  - Neurons of the dorsal root ganglia (DRG) express a diversity of voltage-gated
      sodium channels. From rat DRG we have cloned and functionally expressed a
      tetrodotoxin-sensitive sodium channel alpha subunit, NaCh6/Scn8a/rPN4, and a
      splice variant, rPN4a. Primary structure analysis shows NaCh6/Scn8a/rPN4 to be
      highly homologous (99%) to NaCh6 and most likely represents the same transcript.
      The splice variation in rPN4a is homologous in sequence and location to that of
      rat brain I. Tissue distribution analyzed by RT-PCR showed NaCh6/Scn8a/rPN4 to be
      expressed at its highest levels in rat brain, at moderate levels in spinal cord,
      and at lower levels in DRG, nodose ganglia, and superior cervical ganglia and to
      be absent from sciatic nerve, heart, and skeletal muscle. In contrast, rPN4a
      shows no expression in brain and low-level expression in spinal cord, whereas in
      DRG its expression is comparable to that of NaCh6/Scn8a/rPN4. Functional analysis
      of these channels expressed in Xenopus oocytes showed that NaCh6/Scn8a/rPN4 and
      rPN4a exhibited similar properties, with V(1/2) approximately -100 mV for steady
      state inactivation and V(1/2) approximately -40 mV for activation. rPN4a
      recovered from inactivation significantly faster than NaCh6/Scn8a/rPN4.
      NaCh6/Scn8a/rPN4 was inhibited by tetrodotoxin with an IC50 approximately 1 nM.
      Coexpression of the beta1 subunit accelerated inactivation kinetics, but the
      beta2 subunit was without effect.

PMID- 9603191
TI  - Effects of C-terminal truncation of the recombinant delta-opioid receptor on
      phospholipase C and adenylyl cyclase coupling.
AB  - Opioid receptors belong to the superfamily of guanine nucleotide binding (G)
      protein-coupled receptors. There is now growing evidence in support of a
      stimulatory coupling of opioid receptors to phospholipase C (PLC), via a
      pertussis toxin-sensitive G protein, leading to the generation of the second
      messenger inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]. We have generated two C
      terminal truncation mutants of the delta-opioid receptor lacking the final 15 or
      37 amino acids and examined their coupling to PLC and adenylyl cyclase. D
      [Pen(2,5)]-enkephalin (DPDPE) mediated Ins(1,4,5)P3 formation and cyclic AMP
      inhibition was measured in whole cells and assayed using radioreceptor mass
      assays. DPDPE produced a time- and dose-dependent increase in Ins(1,4,5)P3 mass
      formation in Chinese hamster ovary (CHO) cells expressing the delta(wt), delta15,
      and delta37 receptors. As the C terminus was truncated, the time to maximum
      stimulation (15 s in CHO delta(wt), 60 s in CHO delta15, and 120 s in CHO
      delta37) increased and removal of the C terminus resulted in a prompt return to
      basal Ins(1,4,5)P3 levels. Whereas the dose-response curves to Ins(1,4,5)P3
      formation and cyclic AMP inhibition remained largely unaffected by C-terminal
      truncation, there were large differences in the pEC/IC50 values, with cyclic AMP
      inhibition being the more potent, perhaps indicating G(i alpha) coupling to
      adenylyl cyclase and G(i beta/gamma) coupling to PLC. Collectively, these data
      indicate that the C terminus of the delta-opioid receptor is unimportant in the
      acute coupling to adenylyl cyclase but may have a role to play in PLC coupling.
      We hypothesize that an intact C terminus is required to allow normal "strong"
      coupling of receptor to Gi and that truncation weakens this link as reflected in
      an increased time to peak. In addition, if the coupling is weak, the acute
      response to agonist stimulation rapidly uncouples.

PMID- 9603192
TI  - Cloning and characterization of a mouse sigma1 receptor.
AB  - A cDNA clone (S2-1a) isolated from a mouse brain cDNA library, using a guinea pig
      sigma1 cDNA as probe, has high homology to the predicted protein sequence of the
      guinea pig (88%) and human (90%) sigma1 receptors. Northern analysis revealed a
      major mRNA of approximately 1.8 kb in a wide range of mouse tissues, with highest
      levels in brain, liver, kidney, and thymus. Southern analysis and chromosomal
      mapping in the mouse suggested a single-copy gene in region A5-B2 of chromosome
      4. Expression of the clone in MCF-7 and CHO cells led to a pronounced increase in
      (+)-[3H]pentazocine binding with a selectivity profile consistent with sigma1
      receptors. In vitro translation yielded a protein of approximately 28 kDa, as did
      transfection of a probe containing the hemagglutinin (HA) epitope (S2-1a.HA) into
      CHO cells, as determined by western analysis using an antibody directed against
      HA. (+)-[3H]-Pentazocine binding to immunopurified HA-tagged receptor
      demonstrated conclusively that S2-1a.HA encodes a high-affinity (+)
      [3H]pentazocine binding site with characteristics of a murine sigma1 receptor. An
      antisense oligodeoxynucleotide designed from S2-1a potentiated opioid analgesia
      in vivo.

PMID- 9603193
TI  - Glucocorticoid-dependent action of neural crest factor AP-2: stimulation of
      phenylethanolamine N-methyltransferase gene expression.
AB  - AP-2 is a vertebrate transcription factor expressed in neural crest cells and
      their derivative tissues, including the adrenal medulla, where epinephrine is
      produced. AP-2 is shown to stimulate expression of the gene encoding the
      epinephrine biosynthetic enzyme phenylethanolamine N-methyltransferase (PNMT).
      However, stimulation of the PNMT gene by AP-2 requires glucocorticoids and
      appears to be mediated through the interaction of AP-2 with activated type II
      glucocorticoid receptors. Mutation of AP-2 and/or glucocorticoid receptor binding
      elements within the PNMT promoter disrupts the ability of AP-2 and
      glucocorticoids to induce PNMT promoter activity. These findings suggest, in the
      case of PNMT, that AP-2 stimulates gene expression through a novel glucocorticoid
      dependent mechanism.

PMID- 9603194
TI  - Evidence of type I and type II transforming growth factor-beta receptors in
      central nervous tissues: changes induced by focal cerebral ischemia.
AB  - The peptides of the transforming growth factor-beta (TGF-beta) family transduce
      their signal through ligand-induced heteromeric complexes that consist of type I
      and type II serine/threonine kinases. Both TGF-beta receptors are abundant in
      many peripheral tissues, but clear evidence of their expression in cortical
      astrocytes and neurons has not been published so far. In this study, we
      investigated the expression of type I and type II TGF-beta receptors and their
      potential ligands (TGF-beta1, TGF-beta2, and TGF-beta3) in the CNS by using RT
      PCR and immunohistochemistry. Moreover, to further the study of those cell types
      that exhibit TGF-beta isoforms and related receptors, we examined through the use
      of RT-PCR whether cortical neurons and astrocytes in culture express the mRNAs
      for TGF-betas and their receptors. We show that the three TGF-beta isoform mRNAs
      are present in the CNS. However, although astrocytes in culture display all three
      isoforms, neurons in culture express only TGF-beta2. We have demonstrated that
      both type I and type II TGF-beta receptor mRNAs and proteins are present in the
      CNS and in cultures of cortical neurons and astrocytes. Thus, TGF-betas may act
      as autocrine and paracrine signals in the CNS between both neurons and astrocytes
      via the same receptor systems as those found in peripheral tissues. TGF-beta1 has
      been shown to be induced following hypoxic-ischemic brain injury and may play a
      critical role in the pathophysiology of degenerative processes in the CNS. In the
      present investigation, we confirmed that the expression of TGF-beta1 was
      increased markedly up until 24 h and thereafter was stable over the first 3 days
      following permanent occlusion of the middle cerebral artery in mice. However,
      whereas the expression of the type I TGF-beta receptor was not altered by the
      ischemic insult, the pattern of the type II TGF-beta receptors was modified
      dramatically in the ischemic area 3 days after the occlusion. These data show
      that, even if ligands are present, they may not be able to transduce their
      signal. Finally, the present study clearly demonstrates that a knowledge of the
      expression of ligand-specific receptors following brain injury is a fundamental
      step in clarifying the involvement of cytokines in neurodegenerative diseases.

PMID- 9603195
TI  - Bcl-2 protects against apoptosis in neuronal cell line caused by thapsigargin
      induced depletion of intracellular calcium stores.
AB  - The toxicity of thapsigargin, a selective inhibitor of endoplasmic reticular Ca2+
      ATPase, was investigated in GT1-7 cells, a murine hypothalamic cell line.
      Treatment of these cells with 50 or 100 nM thapsigargin greatly reduced cell
      viability at 24 and 48 h. These doses of thapsigargin induced a rapid rise in
      free cytosolic Ca2+ ([Ca2+]i), followed by a sustained increase. Addition of EGTA
      to chelate extracellular Ca2+ diminished somewhat the size of the initial
      increase of [Ca2+]i caused by thapsigargin, and abolished the sustained increase.
      The sustained increase could also be abolished by addition of La3+ and by SKF
      96365, a drug selective for receptor-mediated calcium entry, but not by verapamil
      or flunarizine. Pretreatment with 50 microM BAPTA/AM, a cytosolic Ca2+ chelator,
      inhibited the peak [Ca2+]i caused by thapsigargin but did not inhibit the
      sustained elevation of [Ca2+]i. Neither EGTA nor BAPTA/AM inhibited the cell
      death induced by thapsigargin. The cell death was characterized by DNA
      fragmentation ("laddering"), nuclear condensation and fragmentation, and was
      inhibited by protein synthesis inhibitor cycloheximide, all characteristic of
      apoptotic cell death. Overexpression of the protooncogene bcl-2 in GT1-7 cells
      inhibited significantly DNA fragmentation, nuclear condensation and
      fragmentation, and cell death induced by thapsigargin. However, Bcl-2 did not
      alter either basal [Ca2+]i or the elevation of [Ca2+]i induced by thapsigargin.
      Our results suggest that abnormal Ca2+ release from endoplasmic reticulum caused
      by thapsigargin induces GT1-7 death by apoptosis and that this effect does not
      depend on Ca2+ influx from the extracellular space. Bcl-2 inhibited apoptosis
      induced by thapsigargin, but the mechanism is unlikely to be inhibition of
      endoplasmic reticular Ca2+ release in GT1-7 neuronal cells.

PMID- 9603196
TI  - The c-erbA alpha protooncogene induces apoptosis in glial cells via a protein
      kinase C- and bcl-2-suppressible mechanism.
AB  - The c-erbA protooncogene encodes the thyroid hormone (3,5,3'-triiodothyronine;
      T3) receptor alpha1 (TR alpha1). c-erbA/TR alpha1 is expressed in many cell types
      including glial cells, particularly in the immature state. We show here by
      morphological and biochemical criteria that c-erbA induces apoptosis of glial
      B3.1 cells in serum-deprived conditions. This effect is mostly T3 independent.
      Growth factors such as platelet-derived growth factor, basic fibroblast growth
      factor, or transforming growth factor-alpha prevent B3.1 + TR alpha1 cell death.
      Protein kinase C (PKC) activators also prevent the apoptosis phenomenon, an
      effect that was blocked by the PKC-specific inhibitor GF109203X. Expression of an
      exogenous bcl-2 gene led also to B3.1 + TR alpha1 cell survival. Neither a series
      of inhibitors including GF109203X nor T3 inhibits bcl-2 action, indicating that
      bcl-2 blocks a downstream step in the death-promoting process. B3.1 + TR alpha1
      cell apoptosis is not blocked by caspase-1 or poly-ADP-ribosyltransferase
      inhibitors, suggesting that the activation of these classic pathways is not
      involved in the apoptotic mechanism. In addition, direct interaction with
      specific neuronal cells but not incubation with their conditioned medium inhibits
      also apoptosis of B3.1 + TR alpha1 cells. Our results show that c-erbA promotes
      an apoptotic process in glial B3.1 cells that is suppressible by PKC activation
      and bcl-2, probably by distinct mechanisms.

PMID- 9603197
TI  - Effects of a peptide analogue of the amphiphilic domain of the common
      neurotrophin receptor on nerve growth factor-mediated motility of human
      neuroblastoma cells.
AB  - Exposure of human neuroblastoma cells (IMR-32) to a peptide mimic of the
      cytoplasmic amphiphilic domain of the common neurotrophin receptor (p75NTR 367
      379) resulted in enhanced nerve growth factor (NGF)-mediated inhibition of cell
      invasion in vitro. The peptide also enhanced NGF-mediated neurite extension and
      GAP-43 gene expression but had no effect on NGF-mediated cell survival. These
      latter functional effects mimicked influences on NGF-mediated neurite growth in
      other trkA-positive cells as reported previously. NGF-dependent trkA
      phosphorylation was significantly enhanced by the presence of the peptide,
      whereas high-affinity binding of 125I-NGF, both NGF receptors mRNA and protein
      expression, and trkA dimer/monomer ratios were not influenced. The studies
      suggest that ligand-mediated trkA activation has differential effects on cell
      motility phenomena and that the amphiphilic domain of p75NTR has a role in this
      differential signaling.

PMID- 9603198
TI  - Defining responsiveness of avian cochlear neurons to brain-derived neurotrophic
      factor and nerve growth factor by HSV-1-mediated gene transfer.
AB  - The importance of individual members of the neurotrophin gene family for avian
      inner ear development is not clearly defined. Here we address the role of two
      neurotrophins, brain-derived neurotrophic factor (BDNF) and nerve growth factor
      (NGF), for innervation of the chicken cochlea. We have used defective herpes
      simplex virus type 1 (HSV-1) vectors, or amplicons, to express these
      neurotrophins in dissociated cultures of cochlear neurons. HSV-1-mediated
      expression of BDNF promotes neuronal survival similar to the maximal level seen
      by exogenously added BDNF and exceeds its potency to produce neurite outgrowth.
      In contrast, cochlear neurons transduced with an amplicon producing bioactive NGF
      show no response. These results confirm BDNF as an important mediator of
      neurotrophin signaling inside avian cochlear neurons. However, these neurons can
      be rendered NGF-responsive by transducing them with the high-affinity receptor
      for NGF, TrkA. This study underlines the usefulness of amplicons to study and
      modify neurotrophin signaling inside neurons.

PMID- 9603199
TI  - Possible involvement of phosphatidylinositol 3-kinase in regulated exocytosis:
      studies in chromaffin cells with inhibitor LY294002.
AB  - Several lines of evidence suggest that phosphorylated products of
      phosphatidylinositol play critical functions in the regulation of membrane
      trafficking along the secretory pathway. To probe the possible involvement of
      phosphatidylinositol 3-kinase (PI 3-kinase) in regulated exocytosis, we have
      examined its subcellular distribution in cultured chromaffin cells by
      immunoreplica analysis and confocal immunofluorescence. We found that the PI 3
      kinase heterodimer consisting of the regulatory and catalytic subunits was
      associated essentially with the subplasmalemmal cytoskeleton in both resting and
      nicotine-stimulated chromaffin cells. Attempts to immunoprecipitate PI 3-kinase
      with anti-phosphotyrosine antibodies failed, suggesting that the activity of PI 3
      kinase was not modulated by tyrosine phosphorylation and/or physical interaction
      with SH2-containing proteins in stimulated chromaffin cells. LY294002 [2-(4
      morpholinyl)-8-phenyl-4H-1-benzopyran-4-one], a potent inhibitor of PI 3-kinase,
      produced a dose-dependent inhibition of catecholamine secretion evoked by various
      secretagogues. Furthermore, cytochemical experiments with rhodamine-labeled
      phalloidin revealed that LY294002 blocked the disassembly of cortical actin in
      chromaffin cells stimulated by a depolarizing concentration of potassium. Our
      results suggest that PI 3-kinase may be one of the important regulatory
      exocytotic components involved in the signaling cascade controlling actin
      rearrangements required for catecholamine secretion.

PMID- 9603200
TI  - Prostaglandin E2 and 4-aminopyridine prevent the lipopolysaccharide-induced
      outwardly rectifying potassium current and interleukin-1beta production in
      cultured rat microglia.
AB  - Brain inflammation includes microglial activation and enhanced production of
      diffusible chemical mediators, including prostaglandin E2. Prostaglandin E2 is
      generally considered a proinflammatory molecule, but it also promotes neuronal
      survival and down-regulates some aspects of microglial activation. It remains
      unknown, however, if and how prostaglandin E2 prevents microglial activation. In
      primary culture, microglial activation is predicted by a characteristic pattern
      of whole-cell potassium currents and interleukin-1beta production. We
      investigated if prostaglandin E2 could alter these currents and, if so, whether
      these currents are necessary for microglial activation. Microglia were isolated
      from mixed cell cultures prepared from neonatal rat brains and exposed to 0-10
      microM prostaglandin E2 and lipopolysaccharide for 24 h. Currents were elicited
      by using standard patch-clamp technique, and interleukin-1beta production was
      measured by ELISA. Peak outward current densities in microglia treated with
      lipopolysaccharide plus prostaglandin E2 (10 nM) were reduced significantly from
      those of cells treated with lipopolysaccharide alone. Prostaglandin E2 and 4
      aminopyridine (a blocker of outward potassium currents) also significantly
      reduced interleukin-1beta production. Thus, although prostaglandin E2 is
      classified generally as a proinflammatory chemical, it has complex roles in brain
      inflammation that include preventing microglial activation, perhaps by reducing
      the outward potassium current.

PMID- 9603201
TI  - Multiple amphiphysin II splice variants display differential clathrin binding:
      identification of two distinct clathrin-binding sites.
AB  - Amphiphysin I and II are nerve terminal-enriched proteins that display src
      homology 3 domain-mediated interactions with dynamin and synaptojanin. It has
      been demonstrated that the amphiphysins also bind to clathrin, and we have
      proposed that this interaction may help to target synaptojanin and dynamin to
      sites of synaptic vesicle endocytosis. To understand better this potential
      functional role, we have begun to characterize clathrin-amphiphysin interactions.
      Using PCR from adult human cortex cDNA, we have cloned a number of amphiphysin II
      splice variants. In in vitro binding assays, the amphiphysin II splice variants
      display differential clathrin binding and define a 44-amino acid region mediating
      the interaction. Amphiphysin II truncation and deletion mutants identify two
      distinct clathrin-binding domains within this region: one with the sequence
      LLDLDFDP, the second with the sequence PWDLW. Both domains are conserved in
      amphiphysin I, and saturation binding analysis demonstrates that both sites bind
      clathrin with approximately equal affinity. The elucidation of clathrin as a
      splice-specific binding partner for amphiphysin II begins to address the
      potential functional role(s) for the multiple amphiphysin II splice variants and
      further supports an important function for clathrin-amphiphysin interactions in
      protein targeting during endocytosis.

PMID- 9603202
TI  - Intracellular free calcium dynamics in stretch-injured astrocytes.
AB  - We have previously developed an in vitro model for traumatic brain injury that
      simulates a major component of in vivo trauma, that being tissue strain or
      stretch. We have validated our model by demonstrating that it produces many of
      the posttraumatic responses observed in vivo. Sustained elevation of the
      intracellular free calcium concentration ([Ca2+]i) has been hypothesized to be a
      primary biochemical mechanism inducing cell dysfunction after trauma. In the
      present report, we have examined this hypothesis in astrocytes using our in vitro
      injury model and fura-2 microphotometry. Our results indicate that astrocyte
      [Ca2+]i is rapidly elevated after stretch injury, the magnitude of which is
      proportional to the degree of injury. However, the injury-induced [Ca2+]i
      elevation is not sustained and returns to near-basal levels by 15 min postinjury
      and to basal levels between 3 and 24 h after injury. Although basal [Ca2+]i
      returns to normal after injury, we have identified persistent injury-induced
      alterations in calcium-mediated signal transduction pathways. We report here, for
      the first time, that traumatic stretch injury causes release of calcium from
      inositol trisphosphate-sensitive intracellular calcium stores and may uncouple
      the stores from participation in metabotropic glutamate receptor-mediated signal
      transduction events. We found that for a prolonged period after trauma astrocytes
      no longer respond to thapsigargin, glutamate, or the inositol trisphosphate
      linked metabotropic glutamate receptor agonist trans-(1S,3R)-1-amino-1,3
      cyclopentanedicarboxylic acid with an elevation in [Ca2+]i. We hypothesize that
      changes in calcium-mediated signaling pathways, rather than an absolute elevation
      in [Ca2+]i, is responsible for some of the pathological consequences of traumatic
      brain injury.

PMID- 9603203
TI  - SCLIP: a novel SCG10-like protein of the stathmin family expressed in the nervous
      system.
AB  - Stathmin is a cytosolic phosphoprotein previously described as a ubiquitous relay
      integrating various signaling pathways. It is the generic element of a protein
      family in mammals as in Xenopus, including SCG10, a neuron-specific, growth
      associated protein, and RB3/XB3, related to the expression of differentiated
      functions of mature cells of the nervous system. In an extensive search for other
      members of the stathmin family, we identified cDNAs coding for two novel stathmin
      related proteins: (a) a cDNA from a rat striatum cDNA library codes for RB3", a
      splice variant of RB3, with an additional basic domain in its N-terminal region;
      and (b) another cDNA identified through a systematic search in EST databases
      codes for a novel protein, SCLIP, for "SCG10-like protein," displaying 70%
      identity with SCG10 and sharing the same domain organization, with an N-terminal
      domain likely involved in membrane attachment and a C-terminal stathmin-like
      domain. Northern blot analysis as well as in situ hybridization on 14-day rat
      embryos showed that SCLIP mRNA is expressed only in neural structures. SCLIP mRNA
      is expressed at comparable levels in neonatal and adult rat brain, suggesting a
      potential role not only in the acquisition, but also in the expression of
      differentiated neuronal functions.

PMID- 9603204
TI  - Geranylgeraniol overcomes the block of cell proliferation by lovastatin in C6
      glioma cells.
AB  - It is well documented that 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors
      prevent cultured mammalian cells from progressing through the cell cycle,
      suggesting a critical role for a mevalonate-derived product. Recently, it has
      been shown that free geranylgeraniol (GG-OH) and farnesol (F-OH) can be utilized
      by C6 glioma cells for protein isoprenylation. The ability of GG-OH and F-OH to
      restore protein geranylgeranylation or farnesylation selectively has enabled us
      to examine the possibility that mevalonate is essential for cell proliferation
      because it is a precursor of farnesyl pyrophosphate or geranylgeranyl
      pyrophosphate, the isoprenyl donors involved in the posttranslational
      modification of key regulatory proteins. In this study we report that GG-OH, as
      well as mevalonate, overcomes the arrest of cell proliferation of C6 glioma cells
      treated with lovastatin, as assessed by increased cell numbers and a stimulation
      in [3H]thymidine incorporation. The increase in cell number and [3H]thymidine
      incorporation were significantly lower when F-OH was added. Under these
      conditions [3H]mevalonate and [3H]GG-OH are actively incorporated into a set of
      isoprenylated proteins in the size range of small, GTP-binding proteins (19-27
      kDa) and a polypeptide with the molecular size (46 kDa) of the smaller isoform of
      2 ',3'-cyclic nucleotide 3'-phosphodiesterase. Analysis of the proteins
      metabolically labeled by [3H]mevalonate and [3H]GG-OH reveals the presence of
      labeled proteins containing geranylgeranylated cysteinyl residues. Consistent
      with geranylgeranylated proteins playing a critical role in the entry of C6 cells
      into the cell cycle, a (phosphonoacetamido)oxy derivative of GG-OH, a drug
      previously shown to interfere with protein geranylgeranylation, prevented the
      increase in cell number when mevalonate or GG-OH was added to lovastatin-treated
      cells. These results strongly suggest that geranylgeranylated proteins are
      essential for progression of C6 cells into the S phase of the cell cycle and
      provide the first evidence that the "salvage" pathway for the utilization of the
      free isoprenols is physiologically significant in the CNS.

PMID- 9603205
TI  - Toxicity of dopamine to striatal neurons in vitro and potentiation of cell death
      by a mitochondrial inhibitor.
AB  - Intrastriatal injections of the mitochondrial toxins malonate and 3
      nitropropionic acid produce selective cell death similar to that seen in
      transient ischemia and Huntington's disease. The extent of cell death can be
      attenuated by pharmacological or surgical blockade of cortical glutamatergic
      input. It is not known, however, if dopamine contributes to toxicity caused by
      inhibition of mitochondrial function. Exposure of primary striatal cultures to
      dopamine resulted in dose-dependent death of neurons. Addition of medium
      supplement containing free radical scavengers and antioxidants decreased neuronal
      loss. At high concentrations of the amine, cell death was predominantly
      apoptotic. Methyl malonate was used to inhibit activity of the mitochondrial
      respiratory chain. Neither methyl malonate (50 microM) nor dopamine (2.5 microM)
      caused significant toxicity when added individually to cultures, whereas
      simultaneous addition of both compounds killed 60% of neurons. Addition of
      antioxidants and free radical scavengers to the incubation medium prevented this
      cell death. Dopamine (up to 250 microM) did not alter the ATP/ADP ratio after a 6
      h incubation. Methyl malonate, at 500 microM, reduced the ATP/ADP ratio by
      approximately 30% after 6 h; this decrease was not augmented by coincubation with
      25 microM dopamine. Our results suggest that dopamine causes primarily apoptotic
      death of striatal neurons in culture without damaging cells by an early adverse
      action on oxidative phosphorylation. However, when combined with minimal
      inhibition of mitochondrial function, dopamine neurotoxicity is markedly
      enhanced.

PMID- 9603206
TI  - Cyclic AMP-elevating agents prevent oligodendroglial excitotoxicity.
AB  - Previously, we have demonstrated that cells of the oligodendroglial lineage
      express non-NMDA glutamate receptor genes and are damaged by kainate-induced Ca2+
      influx via non-NMDA glutamate receptor channels, representing oligodendroglial
      excitotoxicity. We find in the present study that agents that elevate
      intracellular cyclic AMP prevent oligodendroglial excitotoxicity. After
      oligodendrocyte-like cells, differentiated from the CG-4 cell line established
      from rat oligodendrocyte type-2 astrocyte progenitor cells, were exposed to 2 mM
      kainate for 24 h, cell death was evaluated by measuring activity of lactate
      dehydrogenase released into the culture medium. Released lactate dehydrogenase
      increased about threefold when exposed to 2 mM kainate. Kainate-induced cell
      death was prevented by one of the following agents: adenylate cyclase activator
      (forskolin), cyclic AMP analogues (dibutyryl cyclic AMP and 8-bromo-cyclic AMP),
      and cyclic AMP phosphodiesterase inhibitors (3-isobutyl-1-methylxanthine,
      pentoxifylline, propentofylline, and ibudilast). Simultaneous addition of both
      forskolin and phosphodiesterase inhibitors prevented the kainate-induced cell
      death in an additive manner. A remarkable increase in Ca2+ influx (approximately
      5.5-fold) also was induced by kainate. The cyclic AMP-elevating agents caused a
      partial suppression of the kainate-induced increase in Ca2+ influx, leading to a
      less prominent response of intracellular Ca2+ concentration to kainate. The
      suppressing effect of forskolin on the kainate-induced Ca2+ influx was partially
      reversed by H-89, an inhibitor of cyclic AMP-dependent protein kinase. In
      contrast to this, okadaic acid, an inhibitor of protein phosphatases 1 and 2A,
      brought about a decrease in the kainate-induced Ca2+ influx. We therefore
      concluded that cyclic AMP-elevating agents prevented oligodendroglial
      excitotoxicity by cyclic AMP-dependent protein kinase-dependent protein
      phosphorylation, resulting in decreased kainate-induced Ca2+ influx.

PMID- 9603207
TI  - CCAAT/enhancer binding protein beta is a neuronal transcriptional regulator
      activated by nerve growth factor receptor signaling.
AB  - CCAAT/enhancer binding protein beta (C/EBPbeta) is a transcriptional regulator of
      the basic leucine zipper family. By in situ hybridization analysis, we found that
      C/EBPbeta is widely expressed in the CNS of adult mice, including cells of the
      hippocampus and dentate gyrus and cerebellar Purkinje and granule cells.
      Expression of C/EBPbeta had also been reported in the PC12 cell line, which
      undergoes differentiation to neuron-like cells in response to nerve growth factor
      (NGF). We show that C/EBPbeta mRNA expression increases while protein levels
      decrease during differentiation of PC12 cells. In transactivation assays,
      C/EBPbeta activity was stimulated by NGF receptor signaling. Mutations of a
      phosphorylation site for mitogen-activated protein kinase in C/EBPbeta affected
      its capacity to transactivate in a promoter-specific manner. Our data identify
      the C/EBPbeta protein and gene as direct downstream targets of the NGF receptor
      and suggest a role for C/EBPbeta in neurotrophin signaling in the brain.

PMID- 9603208
TI  - High- and low-affinity alpha-[3H]amino-3-hydroxy-5-methylisoxazole-4-propionic
      acid ([3H]AMPA) binding sites represent immature and mature forms of AMPA
      receptors and are composed of differentially glycosylated subunits.
AB  - Quantitative alpha-[3H]amino-3-hydroxy-5-methylisoxazole-4-propionic acid
      ([3H]AMPA) binding autoradiography was performed on frozen-thawed sections from
      rat brain after preincubation at 0 or 35 degrees C for 1 h. Preincubation at 35
      degrees C instead of 0 degrees C resulted in a selective decrease of [3H]AMPA
      binding assayed at a low concentration of [3H]AMPA (50 nM) and an enhancement of
      binding at a high concentration (500 nM). The decrease in [3H]AMPA binding after
      preincubation at 35 degrees C was accompanied with the loss of the lighter
      organelles of P3 (microsomal) fractions. These organelles were found to contain a
      small subpopulation of AMPA/GluR receptors exhibiting a high affinity for
      [3H]AMPA (K(D) approximately 14 nM), whereas heavier organelles exhibited lower
      affinity for AMPA (K(D) approximately 190 nM). This small subpopulation of
      AMPA/GluR receptors contained almost exclusively a structurally distinct species
      of GluR2/3 subunits with an apparent molecular mass of 103.5 kDa (assessed with
      anti-GluR2/3, C-terminal antibodies). Experiments using two deglycosylating
      enzymes, N-glycopeptidase F and endoglycosidase H, clearly indicated that the
      103.5-kDa species represented a partially unglycosylated form of GluR2/3 subunits
      containing the high-mannose type of oligosaccharide moiety, whereas receptors
      present in synaptosomal fractions were composed of subunits with complex
      oligosaccharides. A similar result was obtained by using an antibody recognizing
      the N-terminal domain of GluR2(4). The same enzymatic treatment indicated that
      GluR1 subunits also exhibited a partially glycosylated form. These data indicate
      that high-affinity [3H]AMPA binding sites represent nonsynaptic, intracellular
      membrane-bound AMPA receptors that differ from synaptic receptors by at least the
      glycosylation state of GluR2 (and GluR1) subunits. In addition, our results
      provide a relatively simple way of assessing changes in two spatially and
      structurally distinct [3H]AMPA binding/GluR sites.

PMID- 9603209
TI  - Metabotropic glutamate receptor agonists potentiate cyclic AMP formation induced
      by forskolin or beta-adrenergic receptor activation in cerebral cortical
      astrocytes in culture.
AB  - The metabotropic glutamate receptor (mGluR) agonist 1-aminocyclopentane-1S,3R
      dicarboxylic acid (ACPD) potentiated the accumulation of cyclic AMP induced by
      either beta-adrenergic receptor stimulation (isoproterenol) or direct activation
      of adenylyl cyclase (AC) with forskolin in rat cerebral cortical astrocytes grown
      in a defined medium. In contrast, ACPD inhibits the cyclic AMP response in
      astrocytes cultured in a serum-containing medium. Pharmacological
      characterization indicated that a group I mGluR, of which only mGluR5 is
      detectable in these cells, is involved in the potentiation of cyclic AMP
      accumulation. Potentiation was elicited by mGluR I agonists [e.g., (R,S)-3,5
      dihydroxyphenylglycine (DHPG)], but not by mGluR II or III agonists; it was
      pertussis toxin resistant and abolished by procedures suppressing mGluR5 function
      (phorbol ester pretreatment or DHPG-induced receptor down-regulation).
      Nevertheless, it appears that products generated through the mGluR5 transduction
      pathway, such as elevated [Ca2+]i or activated protein kinase C (PKC), are not
      involved in the potentiation as it was not influenced by either the intracellular
      calcium chelator BAPTA-AM or the PKC inhibitor Ro 31-8220. An inhibitor of
      phospholipase C, U-73122, markedly attenuated mGluR5-activated phosphoinositide
      hydrolysis but did not significantly affect the DHPG potentiation of the cyclic
      AMP response. A mechanism is proposed in which the potentiating effect on AC
      could be mediated by free betagamma complex that is liberated after the agonist
      bound mGluR5 interacts with its coupled G protein.

PMID- 9603210
TI  - Multiple coupling of human D5 dopamine receptors to guanine nucleotide binding
      proteins Gs and Gz.
AB  - We have demonstrated previously that D1 dopamine receptors are coupled to both Gs
      alpha and Go alpha. We examine here the coupling between human D5 dopamine
      receptors and G proteins in transfected rat pituitary GH4C1 cells. Similar to D1
      receptors, cholera toxin treatment of cells reduced, but did not abolish, D5
      agonist high-affinity binding sites, indicating D5 receptors couple to both Gs
      alpha and cholera toxin-insensitive G proteins. The interaction between D5
      receptors and Gs alpha was confirmed by immunoprecipitation studies and by the
      ability of D5 receptors to stimulate adenylyl cyclase. Unlike D1 receptors, D5
      receptors did not display any pertussis toxin-sensitive G-protein coupling to Go
      alpha or Gi alpha. D5 receptors were also not coupled to Gq alpha and were unable
      to mediate phosphatidylinositol metabolism. Instead, D5 sites appeared to be
      coupled to an AIF(-)4-sensitive, N-ethylmaleimide-resistant G protein. Anti-Gz
      alpha caused immunoprecipitation of 24.2 +/- 5.2% of G protein-associated D5
      receptors, indicating coupling between D5 and Gz alpha. The coupling to Gz alpha
      was specific for D5 receptors, because similar associations were not detected
      between D1 receptors and Gz alpha.

PMID- 9603211
TI  - Restoration of norepinephrine and reversal of phenotypes in mice lacking dopamine
      beta-hydroxylase.
AB  - Mice with a targeted disruption of the dopamine beta-hydroxylase (DBH) gene are
      unable to synthesize norepinephrine (NE) and epinephrine. These mice have
      elevated levels of dopamine in most tissues, although the levels are only a
      fraction of those normally found for NE. It is noteworthy that NE can be restored
      to normal levels in many tissues after a single injection of the synthetic amino
      acid precursor of NE, L-threo-3,4-dihydroxyphenylserine (DOPS). In other tissues,
      NE can be restored to normal levels after multiple injections of DOPS, whereas in
      the midbrain and cerebellum, restoration of NE is limited to 25-30% of normal. NE
      levels typically peak approximately 5 h after DOPS administration and are
      undetectable by 48 h. Epinephrine levels are more difficult to restore. The
      elevated levels of dopamine fall modestly after injection of DOPS. S(-)
      Carbidopa, which does not cross the blood-brain barrier, inhibits aromatic L
      amino acid decarboxylase and effectively prevents restoration of NE by DOPS in
      the periphery, while allowing restoration in the CNS. Ptosis and reductions in
      male fertility, hind-limb extension, postdecapitation convulsions, and uncoupling
      protein expression in dopamine beta-hydroxylase-deficient mice are all reversed
      by DOPS injection.

PMID- 9603212
TI  - Recycling of synaptic vesicles at the frog neuromuscular junction in the presence
      of strontium.
AB  - In these experiments, we followed the exocytosis and endocytosis of synaptic
      vesicles with the vital dye FM1-43 and asked whether calcium is important for
      membrane retrieval at the frog neuromuscular junction. We replaced calcium with
      equimolar amounts of strontium and monitored the staining of recycling vesicles
      by inducing exocytosis with electrical stimulation. Trains of 2,400 (2 or 20 Hz)
      or 4,200 (20 Hz) pulses failed to induce FM1-43 internalization in the presence
      of strontium, but they did in the presence of calcium. This effect of strontium
      was not due to a decrease in exocytosis, because FM1-43 release was similar in
      the presence of calcium or strontium. The impairment in endocytosis, observed as
      inhibition of FM1-43 internalization, could be overcome by longer periods of
      stimulation (6,000 pulses at 2 or 20 Hz) in the presence of strontium (1.8 mM) or
      by increasing the extracellular concentration of strontium to 10 mM (2,400 action
      potentials at 20 Hz). It is suggested that endocytosis is dependent on calcium
      influx and that strontium is much less effective in replacing calcium for
      endocytosis than it is for exocytosis.

PMID- 9603213
TI  - Intraamniotic ethyl docosahexaenoate administration protects fetal rat brain from
      ischemic stress.
AB  - Studies were conducted on the prenatal rat given a single intraamniotic injection
      of ethyl docosahexaenoate (Et-DHA; 9.6-12 mmol per fetus) or subjected to an n-3
      fatty acid-deficient diet to assess the role of docosahexaenoate on oxidative
      stress during episodes of ischemia. A time-dependent decrease in the ability of
      brain slices from animals treated with Et-DHA to produce thiobarbituric acid
      reactive substance (TBARS), most pronounced after 1 day (from 58.1 +/- 4.22 to
      15.9 +/- 1.6 nmol/mg of DNA), was noticed on stimulation with Fe2+. Brain slices
      from fetuses treated for 1 day with Et-DHA and those from untreated fetuses
      produced TBARS levels of 46.7 +/- 6.5 and 114.8 +/- 10.8 nmol/mg of DNA,
      respectively, after a 20-min occlusion of the fetal-maternal circulation at
      embryonic day 20, suggesting a protective effect of Et-DHA. The protective effect
      of a single dose of Et-DHA in utero remained high up to 3 days after injection (p
      < 0.001) and was long-lasting, yet not significant, up to 3 days following birth.
      In agreement with a reduction in TBARS production by slices, the endogenous
      levels of TBARS in brains of Et-DHA-treated animals were lower than in the
      controls. Et-DHA-injected fetuses exhibited significantly higher levels of
      esterified DHA than the noninjected controls. n-3-deficient diet given to dams
      for 2 weeks before birth did not affect the levels of TBARS production in control
      fetal brain slices but abolished the increase caused by ischemia. Et-DHA
      administration for 24 h to n-3-deficient fetuses reduced the amount of TBARS
      produced by the fetal brain slices from 49.1 +/- 8.5 to 31.7 +/- 4.1 nmol/mg of
      DNA. A protective effect from oxidative damage after postischemic oxidative
      stress in fetal brain following DHA supplements is suggested, whereas the effect
      of n-3 fatty acid deficiency in this regard is more ambiguous.

PMID- 9603214
TI  - In vitro studies of ferritin iron release and neurotoxicity.
AB  - The increase in brain iron associated with several neurodegenerative diseases may
      lead to an increased production of free radicals via the Fenton reaction.
      Intracellular iron is usually tightly regulated, being bound by ferritin in an
      insoluble ferrihydrite core. The neurotoxin 6-hydroxydopamine (6-OHDA) releases
      iron from the ferritin core by reducing it to the ferrous form. Iron release
      induced by 6-OHDA and structurally related compounds and two other dopaminergic
      neurotoxins, 1-methyl-4-phenylpyridinium iodide (MPP+) and 1-trichloromethyl
      1,2,3,4-tetrahydro-beta-carboline (TaClo), were compared, to identify the
      structural characteristics important for such release. 1,2,4-Trihydroxybenzene
      (THB) was most effective in releasing ferritin-bound iron, followed by 6-OHDA,
      dopamine, catechol, and hydroquinone. Resorcinol, MPP , and TaClo were
      ineffective. The ability to release iron was associated with a low oxidation
      potential. It is proposed that a low oxidation potential and an ortho
      dihydroxyphenyl structure are important in the mechanism by which ferritin iron
      is mobilized. In the presence of ferritin, both 6-OHDA and THB strongly
      stimulated lipid peroxidation, an effect abolished by the addition of the iron
      chelator deferoxamine. These results suggest that ferritin iron release
      contributes to free radical-induced cell damage in vivo.

PMID- 9603215
TI  - Optical imaging of hippocampal neurons with a chloride-sensitive dye: early
      effects of in vitro ischemia.
AB  - We determined if changes in intraneuronal Cl- occur early after ischemia in the
      hippocampal slice. Slices from juvenile rats (14-19 days old) were loaded with
      the cell-permeant form of 6-methoxy-N-ethylquinolinium chloride (MEQ), a Cl(-)
      sensitive fluorescent dye. Real-time changes in intracellular chloride
      concentration ([Cl-]i) were measured with UV laser scanning confocal microscopy
      in multiple neurons within each slice. In vitro ischemia (26-28 degrees C, 10
      min) was confirmed by the loss of synaptic transmission (evoked field excitatory
      postsynaptic potentials) from pyramidal cells in area CA1. After ischemia and
      reoxygenation (10 min), MEQ fluorescence decreased significantly in CA1 pyramidal
      cells and interneurons. The decreased fluorescence corresponded to an ischemia
      induced increase in [Cl-]i of approximately 10 mM. Pretreatment with the GABA(A)
      gated Cl- channel antagonist picrotoxin (100 microM) blocked the ischemia-induced
      change in [Cl-]i. Analysis of the superfusates indicated that ischemia also
      caused a transient amino acid (GABA, glutamate, and aspartate) release that was
      maximal at approximately 10 min, returning to baseline shortly thereafter.
      Recovery from ischemia was confirmed by the return of synaptic transmission in
      area CA1, the return toward baseline of the ischemia-induced decrease in MEQ
      fluorescence, and exclusion of propidium iodide from MEQ fluorescent cells.
      Furthermore, pyramidal cells did not undergo cell swelling during this early
      phase of reoxygenation, as indicated by the volume-sensitive dye calcein. Thus,
      mild ischemia induces the accumulation of [Cl-]i secondary to GABA(A) receptor
      activation, in the absence of cellular swelling or death. In contrast,
      depolarization of the slice with K+ (50 mM) decreased MEQ fluorescence
      significantly but caused cell swelling. Picrotoxin did not prevent the K+-induced
      increase in [Cl-]i. It is possible that an increased [Cl-]i, following either an
      ischemic event or an episode of depolarization, would reduce the Cl- driving
      force and thereby limit synaptic transmission by GABA. To support this
      hypothesis, ischemia caused a reduction in the ability of the GABA agonist
      muscimol to increase [Cl-]i after 20-min reoxygenation.

PMID- 9603216
TI  - (-)-Deprenyl protects human dopaminergic neuroblastoma SH-SY5Y cells from
      apoptosis induced by peroxynitrite and nitric oxide.
AB  - In Parkinson's disease the cell death of dopamine neurons has been proposed to be
      mediated by an apoptotic death process, in which nitric oxide may be involved.
      This article reports the induction of apoptosis by nitric oxide and peroxynitrite
      in human dopaminergic neuroblastoma SH-SY5Y cells and the antiapoptotic activity
      of (-)-deprenyl. After the cells were treated with a nitric oxide donor, NOR-4,
      or a peroxynitrite donor, SIN-1, DNA damage was quantitatively studied using a
      single-cell gel electrophoresis (comet) assay. NOR-4 and SIN-1 induced DNA damage
      dose-dependently. Cycloheximide and alkaline treatment of the cells prevented the
      DNA damage, indicating that the damage is apoptotic and that it depends on the
      intracellular signal transduction. Superoxide dismutase and the antioxidants
      reduced glutathione and alpha-tocopherol protected the cells from the DNA damage.
      (-)-Deprenyl protected the cells from the DNA damage induced by nitric oxide or
      peroxynitrite almost completely. The protection by (-)-deprenyl was significant
      even after it was washed from the cells, indicating that (-)-deprenyl may
      activate the intracellular system against apoptosis. These results suggest that (
      )-deprenyl or related compounds may be neuroprotective to dopamine neurons
      through its antiapoptotic activity.

PMID- 9603217
TI  - Nitric oxide production and perivascular tyrosine nitration following focal
      ischemia in neonatal rat.
AB  - Oxygen free radicals and nitric oxide (NO.) have been proposed to be involved in
      acute CNS injury produced by cerebral ischemia; however, controversy remains
      regarding how they cause injury. Because superoxide generation is triggered
      during reperfusion, the cytotoxic oxidant peroxynitrite could be formed, but it
      is not known if this occurs. Dot blot and immunohistochemistry studies were
      performed on the magnitude and time course of tyrosine nitration and inducible NO
      synthase (NOS2) in the postischemic rat pup brain. Neonatal ischemia was induced
      by permanent left middle cerebral artery occlusion in association with 1-h
      occlusion of the left common carotid artery in 7-day-old Wistar pups.
      Nitrotyrosine (NT) immunoreactivity was evident in the blood vessels close to the
      cortical infarct at 48-72 h of recovery, and T lymphocytes were involved with
      this production. NOS2 immunoreactivity was seen in neutrophils in the same
      vessels and in the parenchyma at 72 h of recirculation. Whereas NT staining
      decreased with time, NOS2-positive neutrophils could be still detected in
      arachnoid vessels at 14 days of recirculation. We conclude that perivascular
      reactions mediated by peroxynitrite are important in the cascade of events that
      lead to brain oxidative stress in neonatal ischemia. Moreover, NO-related species
      may serve as a signaling function instead of directly mediating toxicity.

PMID- 9603218
TI  - Postischemic reperfusion induces alpha-fodrin proteolysis by m-calpain in the
      synaptosome and nucleus in rat brain.
AB  - A membrane cytoskeletal protein, fodrin, is a substrate for a Ca2+-dependent
      protease, calpain. It remains unknown whether mu-calpain or m-calpain is involved
      in the proteolysis of either alpha- or beta-fodrin and in what subcellular
      localization during ischemia and reperfusion of the brain. To address these
      issues, we examined the distribution of fodrin and calpain and the activities of
      calpain and calpastatin (endogenous calpain inhibitor) in the same subcellular
      fractions. Rat forebrain was subjected to ischemia by a combination of occlusion
      of both carotid arteries and systemic hypotension, whereas reperfusion was
      induced by releasing the occlusion. Immunoblotting, activity measurement, and
      casein zymography did not detect the presence of mu-calpain or a significant
      change of m-calpain level after ischemia or reperfusion. However, casein
      zymography revealed a unique Ca2+-dependent protease that was eluted with both
      0.18 and 0.40 M NaCl from a DEAE-cellulose column. Alpha- and beta-fodrins and m
      calpain were found to be rich in the synaptosomal, nuclear, and cytosolic
      subfractions by immunoblotting analysis. Reperfusion (60 min) following ischemia
      (30 min) induced selective proteolysis of alpha-fodrin, which was inhibited by a
      calpain inhibitor, acetylleucylleucylnorleucinal (400 microM, 1 ml, i.v.). The mu
      calpain-specific fragment of beta-fodrin was not generated during ischemia
      reperfusion, supporting the possibility of the involvement of m-calpain rather
      than mu-calpain in the alpha-fodrin proteolysis.

PMID- 9603219
TI  - Membrane instability, plasmalogen content, and Alzheimer's disease.
AB  - The normal stability of the cell membrane bilayer depends on its lipid
      composition being appropriate to the ambient (physiological) temperature, Tp.
      Membrane lipid composition may be altered by disease such that the bilayer is
      only stable at a new critical temperature, T*, which may differ from Tp. In
      Alzheimer's disease (AD) temporal cortex, a defect of lipid composition has
      previously been identified, namely, a decrease in the ratio of plasmalogen to
      nonplasmalogen ethanolamine glycerophospholipids. Furthermore, for AD temporal
      cortex neural membranes, T* << Tp, a finding confirmed in the present study in a
      larger series than previously, using a new method for obtaining T*. This
      inequality between T* and Tp has been proposed as a putative contributory
      pathogenetic mechanism leading to membrane destabilisation in AD brain. The
      plasmalogen deficiency could account for the change in T* in AD, as shown by
      experiments where T* was measured for artificial lipid mixtures simulating brain
      membranes with varying plasmalogen/nonplasmalogen ratios. The critical
      temperature was found to be very sensitive to small alterations in plasmalogen
      content.

PMID- 9603220
TI  - Functional changes in rat nigral GABA(A) receptors induced by degeneration of the
      striatonigral GABAergic pathway: an electrophysiological study of receptors
      incorporated into Xenopus oocytes.
AB  - Expression of rat brain gamma-aminobutyric acid type A (GABA(A)) receptors in
      Xenopus laevis oocytes can be achieved by injection of the oocytes with
      synaptosomes. This approach has now been applied to evaluate changes in the
      function of nigral GABA(A) receptors after degeneration of the striatonigral
      GABAergic pathway induced by the unilateral infusion of kainic acid into the rat
      striatum. Ten days after striatal injection, synaptosomal membranes were prepared
      from the substantia nigra and introduced into oocytes. Nigral GABA(A) receptors
      incorporated into the oocyte cell membrane were then characterized
      electrophysiologically under voltage-clamp conditions. The maximal amplitude of
      GABA-induced Cl- currents in oocytes injected with synaptosomes from denervated
      substantia nigra was twice that observed in oocytes injected with synaptosomes
      from control substantia nigra. The concentration of GABA required for the half
      maximal response did not differ between the two groups of oocytes. In addition,
      the potentiation of GABA-induced currents by the benzodiazepine diazepam (1
      microM) and the steroid derivative allopregnanolone (3 microM) was increased by
      approximately 65 and 60%, respectively, in oocytes injected with synaptosomes
      from denervated substantia nigra compared with those injected with control
      synaptosomes. The concentrations of diazepam and allopregnanolone giving half
      maximal responses were not affected by denervation. In contrast, the inhibitory
      effects of the benzodiazepine receptor inverse agonists FG 7142 (10 microM) and
      6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylic acid ethyl ester (1 microM)
      were reduced by 48 and 38%, respectively, after denervation. These results
      indicate that the up-regulation of nigral GABA(A) receptors induced by
      degeneration of the striatonigral GABAergic pathway is associated with an
      increased efficacy of positive allosteric modulators, such as benzodiazepines and
      steroids, and with a reduced efficacy of negative allosteric modulators such as
      beta-carbolines.

PMID- 9603221
TI  - Distinct effects of imipramine on 5-hydroxytryptamine uptake mediated by the
      recombinant rat serotonin transporter SERT1.
AB  - Tricyclic and nontricyclic serotonin [5-hydroxytryptamine (5-HT)] uptake
      inhibitors are widely used for the treatment of depression. Here, we show that
      both the tricyclic antidepressant imipramine and the nontricyclic antidepressant
      citalopram competitively inhibit 5-HT transport mediated by the recombinant rat 5
      HT transporter SERT1. For citalopram, the concentration producing half-maximal
      transport inhibition was in the same order of magnitude as its K(D) value
      determined by equilibrium binding. In contrast, the inhibitory potency of
      imipramine was more than one order of magnitude lower than its K(D) value. Our
      data are consistent with low-affinity imipramine binding occurring at or close to
      the substrate recognition site, which also binds citalopram. Occupation of the
      high-affinity imipramine binding site on SERT1 did not affect 5-HT transport but
      allosterically displaced citalopram from the substrate recognition site.
      Consequently, low concentrations of imipramine partially protected 5-HT transport
      from citalopram inhibition. This protection was only observed in the presence of
      Na+ because high-affinity imipramine binding is strictly sodium-dependent. Thus,
      depending on which of its binding sites on SERT1 is occupied, imipramine may
      exert distinct effects on 5-HT uptake mediated by the recombinant rat 5-HT
      transporter.

PMID- 9603222
TI  - Calmodulin modulates mitogen-activated protein kinase activation in response to
      membrane depolarization in PC12 cells.
AB  - In the absence of neurotrophic factors, chronic depolarization of plasma membrane
      has been shown to maintain several populations of primary neurons in culture. We
      report that in the PC12 cell line, depolarization causes Ca2+ influx through
      voltage-gated Ca2+ channels, which is able to stimulate extracellular-regulated
      kinase (ERK) activity. We studied which mediators were responsible for ERK
      activation resulting from increased levels of Ca2+ in the cytoplasm and found
      that calmodulin was involved in this process. The addition of W13, a calmodulin
      inhibitor, to the culture medium, prevented ERK activation when PC12 cells were
      depolarized. In addition, we show that high K+ treatment did not induce Trk A
      phosphorylation, thus excluding the possibility of Ca2+ operating through this
      receptor to activate the ERK signal transduction pathway. Moreover, although high
      K+ treatment is able to phosphorylate the epidermal growth factor receptor (EGFR)
      and thus to activate the ERK signal transduction pathway, we demonstrate that W13
      did not alter the state of EGFR phosphorylation in conditions that almost
      completely blocked ERK activation. These data suggest that calmodulin mediates
      ERK activation induced by increases in intracellular Ca2+ concentration in PC12
      cells by a mechanism that seems to be independent of Trk A and EGFR activation.

PMID- 9603223
TI  - Tyrosine hydroxylase in bovine adrenal chromaffin cells: angiotensin II
      stimulated activity and phosphorylation of Ser19, Ser31, and Ser40.
AB  - The aim of this study was to determine the effect of angiotensin II (AII) on
      tyrosine hydroxylase (TOH) activity and phosphorylation in bovine adrenal
      chromaffin cells (BACCs). We report here that stimulation of BACCs with AII (100
      nM) produced a significant increase in both TOH activity and phosphorylation over
      a period of 10 min. The increase in TOH activity was receptor-mediated. Tryptic
      phosphopeptide analysis by HPLC revealed that AII stimulated an increase in
      phosphorylation of three sites on TOH, Ser19, Ser31, and Ser40, with the largest
      increase being observed for Ser31 phosphorylation. Pretreatment of the cells with
      the protein kinase C inhibitor Ro 31-8220 (10 microM, 15 min) did not affect TOH
      activity or phosphorylation produced by AII. The inhibitor also did not affect
      the TOH activity or Ser40 phosphorylation produced by forskolin (10 microM, 10
      min). In contrast, Ro 31-8220 fully inhibited the TOH activation as well as Ser31
      and Ser40 phosphorylation of TOH produced by phorbol 12,13-dibutyrate (500 nM, 10
      min). Removal of extracellular Ca2+ from the incubation medium inhibited the AII
      induced TOH activity by 50% and significantly blocked Ser19 and Ser31
      phosphorylation but did not affect Ser40 phosphorylation in response to AII.
      These results indicate that AII activates a complex and perhaps novel signaling
      pathway leading to the phosphorylation and activation of TOH. The TOH activation
      by AII appears to be partially independent of Ser40 phosphorylation, suggesting a
      potentially important role for Ser31 phosphorylation.

PMID- 9603224
TI  - Regulation of neuroprotective action of vasoactive intestinal peptide in the
      murine developing brain by protein kinase C and mitogen-activated protein kinase
      cascades: in vivo and in vitro studies.
AB  - Intracerebral administration of the excitotoxin ibotenate to newborn mice induces
      white matter lesions mimicking periventricular leukomalacia, the most frequent
      brain lesion occurring in premature human babies. In this model, coinjection of
      vasoactive intestinal peptide prevents white matter lesions. In the present
      study, coadministration of ibotenate, vasoactive intestinal peptide, and
      selective transduction inhibitors showed that protein kinase C and mitogen
      associated protein kinase pathways were critical for neuroprotection. In vivo and
      in vitro immunocytochemistry revealed that vasoactive intestinal peptide
      activated protein kinase C in astrocytes and neurons, and mitogen-associated
      protein kinase in neurons. In vitro neuronal transduction activation was indirect
      and required medium conditioned by astrocytes in which protein kinase C had been
      activated by vasoactive intestinal peptide. Although vasoactive intestinal
      peptide did not prevent the initial in vivo appearance of white matter lesion, it
      promoted a secondary repair of this lesion with axonal regrowth. Through protein
      kinase C activation, vasoactive intestinal peptide also prevented ibotenate
      induced white matter astrocyte death. These data support the following
      hypothetical model: Vasoactive intestinal peptide activates protein kinase C in
      astrocytes, which promotes astrocytic survival and release of soluble factors;
      these released factors activate neuronal mitogen-associated protein kinase and
      protein kinase C, which will permit axonal regrowth.

PMID- 9603225
TI  - Host cell-specific folding of the neuronal nicotinic receptor alpha8 subunit.
AB  - Heterologous expression of the neuronal nicotinic acetylcholine receptor alpha8
      subunit in cultured mammalian cell lines has revealed that the correct folding of
      this protein is dependent on the host cell type. The alpha8 subunit, which is
      able to form homo-oligomeric ion channels when expressed in Xenopus oocytes,
      could be detected in all transfected cell lines by both immunoprecipitation and
      immunofluorescence microscopy with a monoclonal antibody that recognises a linear
      epitope. In contrast, the alpha8 subunit could be detected in some but not in all
      transfected cell lines with a monoclonal antibody that recognises a conformation
      sensitive epitope or by nicotinic radioligand binding. It is interesting that
      although correctly folded alpha8 protein could be detected in transfected rat
      pituitary (GH4C1) cells, only misfolded alpha8 protein could be detected in a
      large subpopulation of transfectants (transient or clonal stable isolates). We
      have also found that the protein encoded by a chimaeric cDNA (constructed from
      the N-terminal region of alpha8 and the C-terminal domain of the serotonin 5-HT3
      receptor subunit) is expressed efficiently, and in a conformation that binds
      alpha-bungarotoxin, in all cell types examined. These results, together with
      previous expression studies with the homo-oligomeric alpha7 subunit and hetero
      oligomeric nicotinic receptor subunit combinations, suggest that the cell
      specific folding described here is a phenomenon that may be characteristic of
      homo-oligomeric nicotinic receptors.

PMID- 9603226
TI  - Identification of lectin-purified neural glycoproteins, GPs 180, 116, and 110,
      with NMDA and AMPA receptor subunits: conservation of glycosylation at the
      synapse.
AB  - The postsynaptic apparatus is associated with a number of glycoproteins with
      apparent molecular masses of 180, 116, and 110 kDa, which are highly concentrated
      in and may be uniquely associated with this structure. These glycoproteins,
      purified by concanavalin A lectin-affinity chromatography, showed
      immunoreactivity in the present study with subunit-specific antibodies to
      glutamate receptors as follows: GP 180, NMDA receptor subunits NR2A/NR2B; GP 116,
      NMDA receptor NR1 (1a); and GP 110, pan-alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionate (pan-AMPA) receptors. Sensitivities to the glycosidases peptide N
      glycosidase F and endo-beta-N-acetylglucosaminidase H on both western blots and
      silver-stained gels suggested that the glutamate receptors were at least major
      constituents of the glycoprotein bands. Similar detailed glycosylation was
      observed for all three glycoproteins, with neutral oligosaccharides being
      dominant. Oligomannosidic glycans (with from five to nine mannoses) accounted for
      approximately 50% of the neutral sugars, with Man 5 (at almost 20% of the neutral
      sugars) always the major glycan. Other abundant neutral oligosaccharides were of
      the complex type. Similar sensitivities to peptide N-glycosidase F and endo-beta
      N-acetylglucosaminidase H were observed for cell line-expressed NMDA receptor
      subunits, suggesting that irrespective of the glycosylation processing available,
      the least highly processed oligosaccharides will be expressed. This may be
      indicative of glycosylation sites in these receptors that are inaccessible to the
      later processing enzymes and favours the oligomannosidic class of glycans in
      functional roles.

PMID- 9603227
TI  - Functional modulation of P2X2 receptors by cyclic AMP-dependent protein kinase.
AB  - It is generally believed that protein phosphorylation is an important mechanism
      through which the functions of voltage- and ligand-gated channels are modulated.
      The intracellular carboxyl terminus of P2X2 receptor contains several consensus
      phosphorylation sites for cyclic AMP (cAMP)-dependent protein kinase (PKA) and
      protein kinase C (PKC), suggesting that the function of the P2X2 purinoceptor
      could be regulated by the protein phosphorylation. Whole-cell voltage-clamp
      recording was used to record ATP-evoked cationic currents from human embryonic
      kidney (HEK) 293 cells stably transfected with the cDNA encoding the rat P2X2
      receptor. Dialyzing HEK 293 cells with phorbol 12-myristate 13-acetate, a PKC
      activator, failed to affect the amplitude and kinetics of the ATP-induced
      cationic current. The role of PKA phosphorylation in modulating the function of
      the P2X2 receptor was investigated by internally perfusing HEK 293 cells with 8
      bromo-cAMP or the purified catalytic subunit of PKA. Both 8-bromo-cAMP and PKA
      catalytic subunit caused a reduction in the magnitude of the ATP-activated
      current without affecting the inactivation kinetics and the value of reversal
      potential. Site-directed mutagenesis was also performed to replace the
      intracellular PKA consensus phosphorylation site (Ser431) with a cysteine
      residue. In HEK 293 cells expressing (S431C) mutant P2X2 receptors, intracellular
      perfusion of 8-bromo-cAMP or purified PKA catalytic subunit did not affect the
      amplitude of the ATP-evoked current. These results suggest that as with other
      ligand-gated ion channels, protein phosphorylation by PKA could play an important
      role in regulating the function of the P2X2 receptor and ATP-mediated
      physiological effects in the nervous system.

PMID- 9603228
TI  - Ontogeny and cellular localization of the pyruvate recycling system in rat brain.
AB  - The ontogeny of the cerebral pyruvate recycling pathway and the cellular
      localization of associated enzymes, malic enzyme (ME) and phosphoenolpyruvate
      carboxykinase (PEPCK), have been investigated using a combination of 13C NMR
      spectroscopy, enzymatic analysis, and molecular biology approaches. Activity of
      the pathway, using [1,2-(13)C2]acetate as a substrate, was detected by 13C NMR in
      brain extracts 3 weeks after birth, increasing progressively up to the third
      month of age. In whole-brain homogenates, ME activity increased to adult levels
      with the same time course as the recycling pathway. PEPCK activity was low during
      the first 2 weeks of life and decreased further toward adulthood. ME and PEPCK
      activity were found in primary cultures of astrocytes and in synaptosomal
      fractions of adult brain. Primary cultures of cortical neurons showed PEPCK
      activity but no detectable ME activity. The cytosolic ME gene was expressed in
      primary cultures of neurons and in astrocytes as well as in the neonatal and
      adult brain. The PEPCK gene was expressed both in primary cultures of cortical
      neurons and in astrocytes, but the level of its expression in the neonatal and
      adult brain was undetectable.

PMID- 9603229
TI  - Role of G protein betagamma subunits in muscarinic receptor-induced stimulation
      and inhibition of adenylyl cyclase activity in rat olfactory bulb.
AB  - In the olfactory bulb, muscarinic receptors exert a bimodal control on cyclic
      AMP, enhancing basal and Gs-stimulated adenylyl cyclase activities and inhibiting
      the Ca2+/calmodulin- and forskolin-stimulated enzyme activities. In the present
      study, we investigated the involvement of G protein betagamma subunits by
      examining whether the muscarinic responses were reproduced by the addition of
      betagamma subunits of transducin (betagamma(t)) and blocked by putative betagamma
      scavengers. Membrane incubation with betagamma(t) caused a stimulation of basal
      adenylyl cyclase activity that was not additive with that produced by carbachol.
      Like carbachol, betagamma(t) potentiated the enzyme stimulations elicited by
      vasoactive intestinal peptide and corticotropin-releasing hormone. RT-PCR
      analysis revealed the expression of mRNAs encoding both type II and type IV
      adenylyl cyclase, two isoforms stimulated by betagamma synergistically with
      activated Gs. In addition, betagamma(t) inhibited the Ca2+/calmodulin- and
      forskolin-stimulated enzyme activities, and this effect was not additive with
      that elicited by carbachol. Membrane incubation with either one of two betagamma
      scavengers, the GDP-bound form of the alpha subunit of transducin and the QEHA
      fragment of type II adenylyl cyclase, reduced both the stimulatory and inhibitory
      effects of carbachol. These data provide evidence that in rat olfactory bulb the
      dual regulation of cyclic AMP by muscarinic receptors is mediated by betagamma
      subunits likely acting on distinct isoforms of adenylyl cyclase.

PMID- 9603230
TI  - Transport is the primary determinant of glycine content in retinal neurons.
AB  - This study demonstrates that in mammalian and nonmammalian species it is possible
      to deplete selectively and reversibly retinal glycinergic neurons of their
      content of glycine by exposure to sarcosine, a competitive inhibitor of glycine
      transporter 1 (glyt-1). This observation was used as a tool to test the
      hypothesis that uptake of glycine rather than de novo synthesis is the main
      determinant of glycine content in retinal neurons. Isolated retinae were depleted
      of immunocytochemically detectable pools of glycine. Thereafter retinae were
      exposed either to physiological medium containing glycine or to medium lacking
      glycine but containing precursors for the synthesis of glycine. Retinae exposed
      to glycine-containing medium rapidly recovered their content of glycine, whereas
      retinae exposed to medium lacking glycine but containing serine, a substrate for
      synthesis of glycine, showed only a slow recovery of immunoreactivity for glycine
      in a few amacrine cells. These data indicate that uptake of glycine is the
      primary determinant of glycine content in most retinal glycinergic neurons. The
      origins of the extracellular pools of glycine remain to be identified; however,
      it is suggested that such glycine may be derived from the vitreous humor and that
      in turn this glycine may be derived from the peripheral circulation.

PMID- 9603231
TI  - Caspases mediate 6-hydroxydopamine-induced apoptosis but not necrosis in PC12
      cells.
AB  - The neurotoxin 6-hydroxydopamine (6-OHDA) induces apoptosis in the rat
      phaeochromocytoma cell line PC12. 6-OHDA-induced apoptosis is morphologically
      indistinguishable from serum deprivation-induced apoptosis. Exposure of PC12
      cells to a low concentration of 6-OHDA (25 microM) results in apoptosis, whereas
      an increased concentration (50 microM) results in a mixture of apoptosis and
      necrosis. We investigated the involvement of caspases in the apoptotic death of
      PC12 cells induced by 6-OHDA, using a general caspase inhibitor,
      benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (zVAD-fmk), and compared this
      with serum deprivation-induced apoptosis, which is known to involve caspases. We
      show that zVAD-fmk (100 microM) completely prevented the apoptotic morphology of
      chromatin condensation induced by exposure to either 6-OHDA (25 and 50 microM) or
      serum deprivation. Furthermore, cell lysates from 6-OHDA-treated cultures showed
      cleavage of a fluorogenic substrate for caspase-3-like proteases (caspase-2, 3,
      and 7), acetyl-Asp-Glu-Val-Asp-aminomethylcoumarin, and this was inhibited by
      zVAD-fmk. However, although zVAD-fmk restored total cell viability to serum
      deprived cells or cells exposed to 25 microM 6-OHDA, the inhibitor did not
      restore viability to cells exposed to 50 microM 6-OHDA. These data show the
      involvement of a caspase-3-like protease in 6-OHDA-induced apoptosis and that
      caspase inhibition is sufficient to rescue PC12 cells from the apoptotic but not
      the necrotic component of 6-OHDA neurotoxicity.

PMID- 9603232
TI  - The need for cautiously extrapolating results obtained with normal animals
      (healthy individuals) to depressed ones.

PMID- 9603233
TI  - Cellular and chemical events during enamel maturation.
AB  - This review focuses on the process of enamel maturation, a series of events
      associated with slow, progressive growth in the width and thickness of apatitic
      crystals. This developmental step causes gradual physical hardening and
      transformation of soft, newly formed enamel into one of the most durable
      mineralized tissues produced biologically. Enamel is the secretory product of
      specialized epithelial cells, the ameloblasts, which make this covering on the
      crowns of teeth in two steps. First, they roughly "map out" the location and
      limits (overall thickness) of the entire extracellular layer as a protein-rich,
      acellular, and avascular matrix filled with thin, ribbon-like crystals of
      carbonated hydroxyapatite. These initial crystals are organized spatially into
      rod and interrod territories as they form, and rod crystals are lengthened by
      Tomes' processes in tandem with appositional movement of ameloblasts away from
      the dentin surface. Once the full thickness of enamel has been formed,
      ameloblasts initiate a series of repetitive morphological changes at the enamel
      surface in which tight junctions and deep membrane infoldings periodically appear
      (ruffle-ended), then disappear for short intervals (smooth-ended), from the
      apical ends of the cells. As this happens, the enamel covered by these cells
      changes rhythmically in net pH from mildly acidic (ruffle-ended) to near
      physiologic (smooth-ended) as mineral crystals slowly expand into the "spaces"
      (volume) formerly occupied by matrix proteins and water. Matrix proteins are
      processed and degraded by proteinases throughout amelogenesis, but they undergo
      more rapid destruction once ameloblast modulation begins. Ruffle-ended
      ameloblasts appear to function primarily as a regulatory and transport epithelium
      for controlling the movement of calcium and other ions such as bicarbonate into
      enamel to maintain buffering capacity and driving forces optimized for surface
      crystal growth. The reason ruffle-ended ameloblasts become smooth-ended
      periodically is unknown, although this event seems to be crucial for sustaining
      long-term crystal growth.

PMID- 9603234
TI  - Molecular biological aspects of acquired bullous diseases.
AB  - Bullous diseases of the oral mucosa and skin were originally classified on the
      basis of clinical and histological criteria. The discovery of autoantibodies in
      some of these patients and the introduction of molecular biology have resulted in
      a new understanding of the pathological mechanisms of many of the bullous
      lesions. In this article, updated topics of the immune-mediated bullous lesions
      which involve oral mucosa and skin are reviewed. Pemphigus antigens, which are
      desmosomal-associated proteins and belong to the cadherin superfamily of cell
      adhesion proteins, have been isolated, and their genes have been cloned. The
      antigens which react with autoantibodies from patients with bullous pemphigoid,
      cicatricial pemphigoid, acquired epidermolysis bullosa, and linear IgA disease
      are all proteins of the hemidesmosome basement membrane complex. Interestingly,
      most of the antigens also appear to be the target for mutations seen in patients
      with the inherited type of epidermolysis bullosa in which bullous lesions are a
      prominent clinical feature.

PMID- 9603235
TI  - Immune defense mechanisms of the dental pulp.
AB  - Defense reactions of the dentin/pulp complex involve a variety of biological
      systems, in which the immune system plays a pivotal role. The knowledge of the
      organization and function of pulpal immunocompetent cells has been sparse, but in
      recent years a significant body of information of immune mechanisms in general
      has provided a footing for substantial new knowledge of the immune mechanisms of
      the dental pulp. The identification of pulpal dendritic cells (DCs) has generated
      research activities which have led to a concept of how an antigenic challenge may
      evoke a pulpal inflammatory response. Although DCs are not able to identify
      foreign antigens specifically, they provide necessary signals to activate T
      lymphocytes which in turn will orchestrate other immunocompetent cells to mount
      the local immune defense of the dental pulp. The purpose of this review is to
      accent the organization and function of pulpal DCs and other tissue and cellular
      components and to provide a basis for how they may interact to instigate pulpal
      defense mechanisms.

PMID- 9603236
TI  - Is all bone the same? Distinctive distributions and properties of non-collagenous
      matrix proteins in lamellar vs. woven bone imply the existence of different
      underlying osteogenic mechanisms.
AB  - The purpose of this review is to summarize recent functional and structural
      findings regarding non-collagenous matrix proteins in bone and teeth, to compare
      gene locations for bone and tooth matrix proteins with loci for hereditary
      skeletal diseases, and to present several provocative hypotheses which integrate
      this new information into a physiological context. Hypothesis I proposes that the
      molecular composition of rapidly deposited and mineralized woven bone, as well as
      the responsiveness of cells synthesizing woven bone to stimuli, is different from
      that for more slowly synthesized lamellar bone, implying the existence of
      distinctive osteogenic mechanisms. This review of recent research strongly
      supports this proposal. Briefly, the protein composition of woven bone matrix is
      enriched in acidic phosphoproteins BAG-75 and BSP, which are not expressed in
      lamellar bone, which is itself enriched in osteocalcin. De novo deposition and
      mineralization of woven bone occurs faster than in lamellar bone by means of a
      matrix-vesicle-assisted mechanism. Deposition of woven bone occurs at sites
      experiencing biomechanical strains higher than those experienced by lamellar
      bone. In addition, woven bone in metaphyseal regions is more susceptible to
      osteoclastic resorption after space flight, ovariectomy, and loss of
      weightbearing than is lamellar bone. Finally, osteoprogenitor cells responsive to
      parathyroid hormone reside in the metaphyseal region of long bones. Taken
      together, these findings suggest that Hypothesis I represents a useful paradigm
      for future studies. Specific functions mediated by most individual bone and tooth
      matrix proteins remain uncertain. A review of current literature suggests that
      the functionality of skeletal matrix proteins is expressed through specific
      binding sites composed of particular species-conserved structural motifs
      (Hypothesis 2). Examples include the previously recognized Asp-Ser-Ser motif of
      dentin phosphophoryns and the gamma-carboxyglutamic acid motif of matrix GLA
      protein and osteocalcin. A new polyacidic amino acid motif composed of
      consecutive Asp and Glu residues (n > 7) was defined in extracellular matrix
      components osteopontin, bone sialoprotein, and bone acidic glycoprotein-75 on the
      basis of strong functional analogies with similar polyacidic stretches in
      divalent metal storage proteins of the endoplasmic reticulum and sarcoplasmic
      reticulum. These structural motifs represent prime targets for future structure
      function studies in vivo and in vitro.

PMID- 9603237
TI  - Neuro-osteology.
AB  - Neuro-osteology stresses the biological connection during development between
      nerve and hard tissues. It is a perspective that has developed since associations
      were first described between pre-natal peripheral nerve tissue and initial
      osseous bone formation in the craniofacial skeleton (Kjaer, 1990a). In this
      review, the normal connection between the central nervous system and the axial
      skeleton and between the peripheral nervous system and jaw formation are first
      discussed. The early central nervous system (the neural tube) and the axial
      skeleton from the lumbosacral region to the sella turcica forms a unit, since
      both types of tissue are developmentally dependent upon the notochord. In
      different neurological disorders, the axial skeleton, including the pituitary
      gland, is malformed in different ways along the original course of the notochord.
      Anterior to the pituitary gland/sella turcica region, the craniofacial skeleton
      develops from prechordal cartilage, invading mesoderm and neural crest cells.
      Also, abnormal development in the craniofacial region, such as tooth agenesis, is
      analyzed neuro-osteologically. Results from pre-natal investigations provide
      information on the post-natal diagnosis of children with congenital developmental
      disorders in the central nervous system. Examples of these are myelomeningocele
      and holoprosencephaly. Three steps are important in clinical neuro-osteology: (1)
      clinical definition of the region of an osseous or dental malformation, (2)
      embryological determination of the origin of that region and recollection of
      which neurological structure has developed from the same region, and (3) clinical
      diagnosis of this neurological structure. If neurological malformation is the
      first symptom, step 2 results in the determination of the osseous region
      involved, which in step 3 is analyzed clinically. The relevance of future neuro
      osteological diagnostics is emphasized.

PMID- 9603238
TI  - Oviduct physiology and sperm/oviduct interactions: an introduction.

PMID- 9603239
TI  - Characteristics of an oviductal glycoprotein and its potential role in the
      fertilization process.

PMID- 9603240
TI  - The modulation of sperm function by the oviductal epithelium.

PMID- 9603241
TI  - The oviductal sperm reservoir in mammals: mechanisms of formation.

PMID- 9603242
TI  - Interleukin-1beta inhibits steroidogenic bioactivity in cultured rat ovarian
      granulosa cells by stimulation of progesterone degradation and inhibition of
      estrogen formation.
AB  - Interleukin (IL)-1beta is a putative regulator of ovulation and perhaps luteal
      function. In this work, we examine its actions on the steroidogenic cascade of
      the rat granulosa cell. Whereas treatment of immature granulosa cells with FSH
      for 72 h produced substantial increments in the accumulation of progesterone, the
      addition of IL-1beta produced dose-dependent inhibition of this FSH effect. Pulse
      labeling of cells with [3H]pregnenolone revealed IL-1beta to effect a decrease in
      the FSH-supported accumulation of [3H]progesterone while enhancing the
      accumulation of its proximal metabolite, [3H]20alpha-dihydroprogesterone. IL
      1beta was without effect on the activity levels of the progesterone-synthesizing
      enzymes, even though the corresponding transcripts were elevated. The effect of
      IL-1beta on some progesterone-degrading enzymes was negligible (5alpha-reductase)
      or modest (3alpha-hydroxysteroid dehydrogenase). In contrast, IL-1beta markedly
      stimulated both control and FSH-supported 20alpha-hydroxysteroid dehydrogenase
      activity (4.8- and 3.3-fold, respectively) and transcripts (16.4- and 7.5-fold,
      respectively). These data demonstrate an IL-1beta-mediated inhibition of
      gonadotropin-stimulated steroidogenesis via modulation of specific enzymes, and
      suggest a role for IL-1beta in mediating the observed decline of these bioactive
      hormones during ovulation and luteolysis.

PMID- 9603243
TI  - Puberty in the female tammar wallaby.
AB  - The growth and timing of female puberty in a seasonally breeding marsupial, the
      tammar wallaby, was examined in wild and captive animals. Puberty, defined as the
      time of first estrus and ovulation, can occur at any time of the year. Sixty
      percent of young wild females went through puberty in late October-November, 3 mo
      before the normal adult mating season in late January-February, but puberty was
      delayed in captive animals kept with a low ratio of males to females. During
      initial cycles, 19% of these captive animals were infertile as judged by failure
      to conceive. In the wild, puberty occurred well before the animals were fully
      grown (body weight 2.0+/-0.3 kg [mean+/-SD], n=23; adult females, 4.7+/-0.6 kg;
      n=34). Only 3% of animals with a body weight below 1.5 kg had ovulated. Thus,
      attainment of a minimum body weight was a key prerequisite associated with
      puberty. Progesterone concentrations in the peripheral plasma of prepubertal
      females were not significantly different from those of adult females during the
      nonbreeding season (prepubertal, 142+/-121 pg/ml, n=34; adult, 194+/-105 pg/ml,
      n=32, p > 0.05). However, there was a significant increase in progesterone (322+/
      242 pg/ml, n=32, p < 0.05) in the postpubertal females (ovulating but still < 3.5
      kg body weight) even though the corpus luteum was quiescent after its formation.
      There was no increase in plasma progesterone before the first estrus. These data
      confirm that estrus does not require a change in the progesterone:estradiol
      ratio, and that a "silent" ovulation does not precede the first estrus in this
      species, so that the onset of puberty coincides with the first behavioral estrus
      and ovulation, when the animals have reached a body weight of 2 kg. Although
      adult female tammars are strict seasonal breeders, with 6 mo of seasonal
      quiescence from the winter to the summer solstice, young females can go through
      puberty at any time of the year. The unique feature of the female tammar wallaby
      is that it does not become a seasonally breeding mammal until after puberty, when
      it has acquired a corpus luteum.

PMID- 9603244
TI  - Developmental changes in the basement membrane of the normal and hypothyroid
      postnatal rat testis: segmental localization of fibulin-2 and fibronectin.
AB  - To characterize developmental changes in the extracellular matrix of the
      postnatal rat testis in relationship to the timing of germ cell maturation, we
      immunolocalized fibulin-1, fibulin-2, and other matrix components in the testes
      of normal and propyl-thiouracil (PTU)-induced hypothyroid animals. Unlike
      laminin, nidogen, and perlecan, which were present in the seminiferous tubule
      basement membrane (BM) throughout postnatal development, fibulins were found to
      disappear from the postnatal tubule BM. Fibulin-1 was no longer detected after
      Day 5 whereas fibulin-2 became localized in a segmental manner within the BM of
      each seminiferous tubule on Days 10 and 15 and disappeared by Day 20. Fibronectin
      showed a segmental pattern in the level of immunostaining of the tubule BM on
      Days 10 and 15, with a more uniform staining seen at earlier and later ages.
      Collagen VI was initially confined to the interstitial matrix in the Day 5 testis
      and became progressively more closely associated with the seminiferous tubule BM
      at later stages. The disappearance of fibulin-2 and the BM-association of
      collagen VI were both delayed in the PTU-treated testes. The developmental
      changes in the staining patterns for fibulin-2 and fibronectin coincide with the
      adhesion and alignment of peritubular cells on the inner seminiferous tubule BM.
      The delay in maturation of the seminiferous tubule BM in the testes of PTU
      treated rats demonstrates a correlation between changes in the composition of the
      tubule BM and cellular development of the testis.

PMID- 9603245
TI  - Progesterone mediates its anti-mitogenic and anti-apoptotic actions in rat
      granulosa cells through a progesterone-binding protein with gamma aminobutyric
      acidA receptor-like features.
AB  - Progesterone (P4) inhibits small granulosa cell (GC) mitosis and large GC
      apoptosis. These actions are steroid specific and dose dependent and are
      inhibited by the progesterone receptor (PR) antagonist, RU-486. However, these
      cells do not express the nuclear PR but rather an ill-defined P4-binding protein
      (P4BP). This binding protein could function as a receptor and mediate P4's
      actions in GCs. Therefore, a series of studies was designed to characterize this
      P4BP. First, an antibody directed against the ligand-binding site of the nuclear
      PR was used in a Western blot analysis. This analysis revealed the presence of a
      60-kDa P4BP within ovarian and GC lysates as well as within an ovarian membrane
      preparation. This protein was not observed in lysates of cells derived from the
      ovarian surface epithelium. In addition, this P4BP was immunoprecipitated by an
      antibody to the alpha1 chain of the gamma aminobutyric acidA (GABA(A)) receptor,
      suggesting that the P4BP could be the ovarian GABA(A) receptor. Since activation
      of the rat ovarian GABA(A) receptor increases intracellular cAMP levels, GCs were
      cultured with control medium supplemented with either 8-bromo-cAMP (8-br-cAMP),
      P4, or muscimol (a GABA agonist). Increases in cAMP were detected by monitoring
      the cAMP-dependent phosphorylation of cAMP response element-binding protein
      (CREB). Phosphorylated CREB was not observed in control or P4-treated cultures,
      but it was detected in the majority of both small and large GCs exposed to either
      8-br-cAMP or muscimol. Since activation of the GABA(A) receptor with muscimol
      increases phosphorylated CREB but P4 does not, this study indicates that P4 does
      not activate the ovarian GABA(A) receptor. However, both bicuculline, a GABA(A)
      receptor antagonist, and the antibody to PR inhibited P4's ability to prevent
      both insulin-dependent mitosis and apoptosis. Collectively, these studies suggest
      that P4 mediates its anti-mitotic and anti-apoptotic effects through this 60-kDa
      P4BP, which has GABA(A) receptor-like properties and is localized within the
      surface membrane of GCs.

PMID- 9603246
TI  - Differential localization of fibroblast growth factor receptor-1, -2, -3, and -4
      in fetal, immature, and adult rat testes.
AB  - Fibroblast growth factors (FGFs) are essential for embryonic development and have
      been implicated in testis development and function. The effects of FGFs are
      mediated through four high-affinity receptors (FGFRs), which have different
      binding affinities for each of the ligands. We have used indirect avidin-biotin
      horseradish peroxidase-enhanced immunohistochemistry to localize FGFR-1, -2, -3,
      and -4 in fetal, immature, and adult rat testes. In the fetal testis,
      immunoreactivity for FGFR-1 was seen in gonocytes, Sertoli cells, Leydig cells,
      and mesenchyme, and FGFR-3 was localized in gonocytes. In the immature testis,
      FGFR-1 was localized to spermatogonia, and all four FGFRs were localized in
      pachytene spermatocytes, immature adultlike Leydig cells, and peritubular cells.
      In the adult testis epithelium, Sertoli cells were immunoreactive for FGFR-4, and
      germ cells were immunoreactive for all four FGFRs, with specific receptors
      localized to specific stages of germ cell development. In the adult testis
      interstitium, FGFR-1, -2, and -4 were localized in Leydig cells, and FGFR-1 and 
      4 were also localized in peritubular cells. The discrete cell- and stage-specific
      localization of FGFRs in the fetal, immature, and adult rat testis suggests that
      FGFs exert specific roles through these receptors in spermatogenesis, Leydig cell
      function, and testicular development.

PMID- 9603247
TI  - Molecular characterization and expression of two ovarian lipoprotein receptors in
      the rainbow trout, Oncorhynchus mykiss.
AB  - Partial cDNAs encoding two lipoprotein receptors were isolated and sequenced from
      the ovary in the rainbow trout (rt), Oncorhynchus mykiss. One of the cDNAs (rt
      LPR) contained the 5 domains characteristic of receptors belonging to the low
      density lipoprotein receptor superfamily. The second cDNA (rt-LP[OS]R) was
      similar to rt-LPR but lacked 105 base pairs encoding the O-linked sugar domain.
      The deduced amino acid sequences of the rt-LPR and rt-LP[OS]R had between 75% and
      80% identity with very-low-density lipoprotein and vitellogenin receptors of
      other species. The rt-lipoprotein receptor mRNAs were approximately 3.5 kilobases
      in size. The rt-LPR was expressed in both the ovary and somatic tissues, whereas
      the rt-LP[OS]R was ovary-specific. Messenger RNA for the lipoprotein receptor(s)
      was expressed at high levels in both pre-vitellogenic (< 0.3 mm) and early
      vitellogenic (up to 1 mm) follicles. Using reverse transcription-polymerase chain
      reaction, expression of rt-LPR and rt-LP[OS]R mRNA was also detected in larger
      vitellogenic follicles (up to 2.5 mm in diameter) but not in follicles in late
      vitellogenesis or in ovulated eggs. The sequence, ovary specificity, and pattern
      of ovarian expression of the rt-LPR mRNA suggest that it encodes the receptor
      that mediates vitellogenin uptake into the ovary.

PMID- 9603248
TI  - Expression of interferon regulatory factors one and two in the ovine endometrium:
      effects of pregnancy and ovine interferon tau.
AB  - Available evidence suggests that interferon tau (IFNtau), the signal for
      pregnancy recognition in ruminants, suppresses transcription of the estrogen
      receptor (ER) gene in the endometrial lumenal epithelium (LE) and superficial
      glandular epithelium (sGE) to prevent oxytocin receptor (OTR) expression and
      pulsatile release of luteolytic prostaglandin F2alpha. The IFN regulatory factors
      one (IRF-1) and two (IRF-2) are transcription factors induced by type I IFNs that
      activate and silence gene expression, respectively. The objectives of these
      studies were to determine effects of pregnancy and IFNtau on expression of
      immunoreactive IRF-1 and IRF-2 proteins in the ovine endometrium. In study one,
      IRF-1 and IRF-2 were not detected in the LE or sGE of cyclic ewes. In pregnant
      ewes, IRF-1 expression was detected transiently in the LE and sGE only on Days 11
      and 13, and IRF-2 was detected in these same epithelia on Days 13, 15, 17, and
      20. In study two, 36 ewes were fitted with uterine catheters on Day 5 of the
      estrous cycle, and one uterine horn was double-ligated at the base. Uterine horns
      of each ewe received twice-daily injections of either recombinant ovine IFNtau or
      control proteins beginning on Day 11 until hysterectomy at 1, 3, 6, 12, 24, 48,
      72, 96, or 120 h after initial injection. The IRF-1 was detected transiently in
      the endometrial LE and sGE only at 12 and 24 h in the uterine horn receiving
      IFNtau but not in those tissues receiving control proteins. The IRF-2 was
      expressed in the LE and sGE at 24 h and thereafter in the IFNtau-treated, but not
      control uterine horns. In control uterine horns, ER and OTR were first detected
      in the LE at 48 h and 72 h, respectively, and remained abundant thereafter. In
      horns receiving IFNtau, ER and OTR expression was not detected in the endometrial
      LE and sGE. Results suggest that IFNtau acts directly on the LE and sGE during
      pregnancy to sequentially induce IRF-1 and then IRF-2 gene expression, which is
      correlated temporally with an absence of ER and OTR. The ovine ER gene may
      contain an IFNtau-responsive element(s) that binds negative-acting, IFNtau
      inducible transcription factors, such as IRF-2, which silences transcription of
      the ER gene in the endometrial epithelium during maternal recognition of
      pregnancy.

PMID- 9603249
TI  - Differentiation of the corpus luteum of the mink (Mustela vison): mitogenic and
      steroidogenic potential of luteal cells from embryonic diapause and
      postimplantation gestation.
AB  - The mink corpus luteum (CL) involutes after ovulation and remains dormant,
      synthesizing low amounts of progesterone until reactivated to terminate embryonic
      diapause. We examined the mitotic and steroid synthetic capacity of luteal cells
      from the diapause and postimplantation phases of mink gestation. Cells from
      diapause divided in vitro, reaching confluence in 7-8 days. Three phenotypes were
      distinguishable: a fusiform cell in whorls, a hypertrophied epithelioid cell, and
      a small epithelioid cell. The first and second cell types divided in vitro after
      confluence, evidenced by localization of proliferating cell nuclear antigen
      (PCNA) in their nuclei. The small epithelioid cells were present in cell nests
      and showed no PCNA activity. Cells derived from reactivated CL did not reach
      confluence and had no PCNA activity. Progesterone accumulation was enhanced in
      luteal cells from diapause by LH, FSH, and dibutyryl (Bu2)cAMP, and by LH and
      (Bu2)cAMP in cells from reactivated CL. In luteal cells from the diapause phase
      of gestation, LH and (Bu2)cAMP induced increases in mRNA coding for steroidogenic
      acute regulatory protein, while cytochrome P450 side-chain cleavage enzyme mRNA
      was increased by prolactin, LH and (Bu2)cAMP. Cellular concentrations of 3beta
      hydroxysteroid dehydrogenase-delta5-4-isomerase mRNA were increased by prolactin
      and (Bu2)cAMP. Thus, luteinization in the mink CL does not engender exit from the
      cell cycle, as both fusiform and hypertrophied cells from diapause divide in
      vitro. Reactivation appears to represent terminal differentiation. LH is capable
      of stimulating steroidogenesis in vitro in luteal cells from diapause, and
      prolactin and LH appear to have both specific and overlapping stimulatory effects
      on the CL of this species.

PMID- 9603250
TI  - Granulosa cell apoptosis induced at the penultimate stage of follicular
      development is associated with increased levels of Fas and Fas ligand in the rat
      ovary.
AB  - Apoptosis of granulosa cells is the cellular mechanism of ovarian follicular
      atresia, and cytokines have been implicated as potential atretogenic factors. We
      therefore investigated the possible role of the cytokine Fas ligand (FasL) and
      its receptor Fas in apoptosis during ovarian follicular atresia induced by
      gonadotropin withdrawal. Immature rats pretreated with eCG were injected 24 h
      later with an antiserum generated against eCG (antibody group) or preimmune
      rabbit serum (control), and ovaries were removed 1 and 24 h after treatment. The
      eCG antiserum caused a dose-dependent inhibition of the significant increase in
      ovarian weight observed between 24 and 48 h after eCG treatment. In situ
      detection of fragmented DNA in histological sections identified cell death in
      atretic but not healthy small and medium-sized antral follicles of the antibody
      group. Cell death was distributed in a scattered pattern throughout the granulosa
      cell layer of small atretic follicles but was localized primarily in granulosa
      cells lining the antral cavity of atretic medium antral follicles.
      Immunohistochemistry of adjacent histological sections revealed intense positive
      immunostaining for Fas and FasL in granulosa cells of atretic small and medium
      antral follicles in a pattern coincidental to the localization of cell death.
      Intense FasL staining was evident in the theca cells of healthy small antral
      follicles. An increase in low molecular weight DNA (DNA "ladders") indicative of
      apoptosis was evident in granulosa cells of the antibody group. Western analysis
      demonstrated increased levels of both Fas and FasL in the granulosa cells of the
      antibody group. These results demonstrate that both Fas and FasL are present in
      ovarian granulosa cells and that FasL may be the signal that induces granulosa
      cell apoptosis during atresia at the penultimate stage of ovarian follicular
      development.

PMID- 9603251
TI  - Development of parthenogenetic and cloned ovine embryos: effect of activation
      protocols.
AB  - Preliminary experiments carried out on ovine oocytes were designed to establish
      correlations between activation protocols and subsequent rates of embryonic
      development. The best activation protocols were thereafter used in studies on
      ovine parthenogenesis and cloning. The first study established that chemical
      activators induce pronuclear development at a slightly higher rate than physical
      activation (ionomycin, 96%; ethanol, 95%; electro activation, 80%). Inhibition of
      second polar body extrusion and one single pronucleus were observed in the
      majority of the oocytes (approximately 90%) treated for 3 h with 6
      dimethylaminopurine (6-DMAP) following either ionomycin or ethanol activation.
      While over 80% of these oocytes cleaved after transfer to the oviducts of
      recipients, progression to the blastocyst stage was higher after ionomycin as
      compared with ethanol activation (58% vs. 19%). The ionomycin plus 6-DMAP
      activation protocol was used to produce parthenogenetic blastocysts whose
      subsequent development was monitored both by ultrasonography and by direct fetal
      examination. Over 70% of parthenogenotes were viable on Day 21 of pregnancy but
      dead by Day 25. The effects of 6-DMAP on nuclear remodeling and fetal development
      of cloned embryos was then investigated. Control cloned embryos underwent nuclear
      envelope breakdown (NEBD), premature chromatin condensation (PCC), and inhibition
      of DNA synthesis. By contrast, reconstructed embryos treated with 6-DMAP
      exhibited intact nuclear membranes, interphase chromatin, and no interference on
      DNA synthesis. Moreover, cloned embryos developed to blastocyst stage in higher
      percentage after 6-DMAP treatment (83% vs. 25%). We conclude that ionomycin
      followed by 6-DMAP incubation yields high percentages of diploid parthenogenetic
      embryos that develop to Day 25 before dying. Cloned embryos activated by the
      ionomycin-6-DMAP protocol develop readily to term.

PMID- 9603253
TI  - Evidence for a luteinizing hormone surge center in the hypothalamus of the pig.
AB  - Studies were conducted to determine whether there is an LH surge generator in the
      hypothalamus of the pig. In experiment 1, 157-day-old ovariectomized (OVX) gilts
      received 1.5 microg estradiol benzoate (EB)/kg BW i.m. every 12 h from 0 through
      24, 48, 72, or 96 h. Blood was sampled every 6 h from 3 to 36 h and every 3 h
      from 36 through 144 h. One of 3, 4 of 4, 4 of 4, and 2 of 3 gilts displayed an LH
      surge after treatment for 24, 48, 72, and 96 h, respectively. With the exception
      that time to maximum LH concentration was greater in gilts treated for 96 h than
      in those treated for 72 h (p < 0.05), parameters of the surge were similar among
      all gilts. In experiment 2a, an Alzet osmotic pump containing EB or vehicle was
      inserted s.c. behind an ear of 124-day-old OVX gilts, resulting in the following
      daily doses of EB: 0, 0.75, 1.50, or 3.00 microg/kg BW. Blood was sampled at 0,
      2, 4, 6, and 8 h and every 8 h thereafter through 168 h to evaluate surge
      secretion of LH, and every 15 min for 8 h starting at 168 h to evaluate pulsatile
      LH secretion. Zero of 3, 0 of 2, 3 of 3, and 3 of 3 gilts displayed an LH surge
      after 0, 0.75, 1.50, and 3.00 microg EB/kg BW, respectively. Parameters of the
      surge were similar among gilts. Pulsatile LH secretion, evaluated 7 days after
      pump insertion, was significantly suppressed for estradiol-treated gilts compared
      to controls. In experiment 2b, at 182 days of age, 10 gilts used in experiment 2a
      plus 2 additional gilts in the original group prepared but not used for
      experiment 2a, were randomly assigned in groups (n=3) to the following daily
      doses of EB: 0, 0.19, 0.38, or 0.75 microg/kg BW, administered again by osmotic
      pump. Treatment and blood-sampling schedules were the same as in experiment 2a.
      Zero, 0, 1, and 2 gilts displayed an LH surge after treatment with 0, 0.19, 0.38,
      and 0.75 microg EB/kg BW, respectively. Parameters of the surge were similar
      among gilts that displayed an LH surge. Pulsatile LH secretion was significantly
      suppressed for estradiol-treated gilts compared to controls. Thus, the LH surge
      resulted from positive feedback stimulation of a specific surge generator rather
      than attenuation or dissipation of negative feedback inhibition of estradiol on a
      pulse generator.

PMID- 9603252
TI  - Regulation of the progesterone receptor and estrogen receptor in decidua basalis
      by progesterone and estradiol during pregnancy.
AB  - In this study we examined the roles of progesterone (P4) and estradiol-17beta
      (E2) in regulation of the P4 receptor (PR) and estrogen receptor (ER) in the
      decidua basalis (DB) during stromal cell proliferation and regression (Days 10
      and 14 of pregnancy, respectively). Pregnant rats were ovariectomized (Ovx) on
      Day 8 or 12 and killed on Day 10 or 14, respectively, following treatment with
      P4, E2, or both. In some experiments, rats received pellets of the anti-progestin
      RU-486 on Day 9 and were killed 3, 6, 12, and 24 h later. Immunolocalization of
      PR and ER showed that both receptors decreased from Day 10 to Day 14. Histologic
      integrity of the placenta and DB were maintained only when P4 was present.
      Control and hormone-treated groups expressed established isoforms of PR and ER:
      PR-B, 110 kDa; PR-A, 80-90 kDa; PR-C, 64-60 kDa; ER-66, 66 kDa; and ER-49, 49
      kDa. On Day 10, expression of PR-A, PR-B, and ER-66 decreased 50-99% (p < 0.05)
      after Ovx or RU-486 treatment but was restored to control levels after Ovx by
      exogenous P4. On Day 14, PR-B and ER-66 declined 66-75% (p < 0.05) after Ovx and
      could not be restored by P4 treatment. Estrogen could not substitute for P4, and
      co-administration of E2 with P4 did not enhance the response over P4 alone. In
      contrast, PR-C was abundantly expressed on Days 10 and 14 in all treatment groups
      after Ovx and RU-486. P4 maintained PR mRNA and ER mRNA after Ovx. Thus,
      regression of the DB may be initiated via changes in relative expression of PR
      isoforms, which result in impaired stromal cell response to P4 action.

PMID- 9603254
TI  - Postovulatory ageing of mouse oocytes in vivo and premature centromere separation
      and aneuploidy.
AB  - Two paramount observations exist regarding aneuploidy in human oocytes: its
      association with maternal age and its more frequent occurrence during meiosis I.
      Numerous experimental studies have shown that fertilization of postovulatory aged
      oocytes is coupled with reproductive failure and cytogenetic aberrations in
      embryos. However, the basic cytogenetic defect(s) of aged oocytes that causes
      these abnormalities has not been adequately described. The objective of this
      study was to test the hypothesis that postovulatory oocyte ageing results in
      increased frequencies of premature centromere separation (PCS) in metaphase II
      (MII) oocytes and aneuploidy in zygotes. MII oocytes and one-cell zygotes were
      collected from superovulated mice at different times after ovulation and
      fertilization. Chromosomes were C-banded and analyzed for structural and
      numerical aberrations. The frequencies of PCS in oocytes significantly (p < 0.01)
      increased with time postovulation: 15 h (15 of 529, 2.8%), 20 h (82 of 627,
      13.1%), and 25 h (118 of 502, 23.5%). In zygotes, the frequencies of hyperploidy
      significantly (p < 0.01) increased with time post-fertilization: 0-4 h (0 of
      260), 4-8 h (5 of 212, 2.4%), and 8-12 h (8 of 262, 3.1%). These data support the
      hypothesis that postovulatory ageing results in elevated levels of PCS in oocytes
      and of aneuploidy in zygotes. The link between PCS and aneuploidy may be random
      segregation of sister chromatids during anaphase II.

PMID- 9603255
TI  - The lipoxygenase inhibitor, nordihydroguaiaretic acid, inhibits ovulation and
      reduces leukotriene and prostaglandin levels in the rat ovary.
AB  - Eicosanoids, the active metabolites of arachidonic acid, are grouped into
      cyclooxygenase products (prostaglandins [PGs] and thromboxanes) and lipoxygenase
      products (leukotrienes [LTs] and lipoxins). Numerous studies suggest a role for
      the lipoxygenase system in ovulation. The aim of this study was to further
      characterize the effects of lipoxygenase inhibition and the interactions of the
      lipoxygenase and cyclooxygenase systems in the rat ovary during ovulation. The
      lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA), was administered in
      vivo and in the isolated perfused rat ovary to determine its effect on ovulation
      rate. The in vivo study confirmed the inhibitory effect of NDGA, and in the
      perfusion experiments, NDGA caused a dose-dependent reduction in the ovulation
      rate. To further define the interaction between the lipoxygenase and
      cyclooxygenase systems, a second set of perfusions was performed with NDGA (10
      microM) and the combination of NDGA (10 microM) plus a nonselective
      cyclooxygenase inhibitor, indomethacin (10 microM). NDGA significantly reduced
      the number of ovulations compared to that in controls. The ovulation rate for the
      combination of NDGA+indomethacin was also significantly lower than in controls
      but not different from that in the NDGA-treated group. Steroidogenesis was
      decreased only in the NDGA+indomethacin perfusions. Ovarian tissue PGE2 and
      PGF2alpha levels in the NDGA-treated ovaries were significantly suppressed
      compared to those in controls. Almost a complete block of PGE2 and PGF2alpha was
      seen in the NDGA+indomethacin group. LTB4 levels in the 10-h-perfused ovarian
      tissues were significantly decreased by NDGA compared to those in control
      tissues. Furthermore, LTB4 (3 microg added twice) completely reversed the
      inhibitory effect of 0.1 microM NDGA on ovulation rate and partially reversed the
      effect of 10 microM NDGA in the perfusion model. These results demonstrate that
      the products of the lipoxygenase pathway, especially LTB4, are important in the
      process of ovulation in this cyclically ovulating species. The interconnected
      lipoxygenase and cyclooxygenase pathways may optimize ovulation and facilitate
      steroidogenesis.

PMID- 9603256
TI  - Seminal transforming growth factor beta1 stimulates granulocyte-macrophage colony
      stimulating factor production and inflammatory cell recruitment in the murine
      uterus.
AB  - Mating in rodents evokes an inflammatory-like reaction within the uterine
      endometrium, characterized by extensive infiltration and activation of
      macrophages, dendritic cells, and granulocytes. This response is initiated when
      seminal vesicle gland-derived factors in the ejaculate stimulate uterine
      epithelial cells to release proinflammatory cytokines including granulocyte
      macrophage colony-stimulating factor (GM-CSF). Experiments in which seminal
      vesicle secretions were fractionated by Sephacryl S-400 chromatography and
      assayed in vitro for GM-CSF-stimulating activity revealed that the seminal moiety
      coeluted with transforming growth factor beta1 (TGFbeta1) in the 150-440-kDa
      range and was neutralized by anti-TGFbeta1 antibodies. Comparable amounts of
      recombinant TGFbeta1 stimulated GM-CSF release in cultures of uterine epithelial
      cells from estrous mice and, when instilled into the uterine lumen, caused an
      increase in GM-CSF content and an infiltration of leukocytes into the endometrium
      similar to the postmating response. These results show that seminal vesicular
      fluid contains TGFbeta1 at levels sufficient to be the primary causative agent in
      the postmating inflammatory cascade through induction of GM-CSF synthesis by
      uterine epithelial cells. Seminal TGFbeta1 is thus implicated as a key factor in
      initiation of the remodeling events and immunological changes that occur in the
      uterus during the preimplantation period of pregnancy.

PMID- 9603257
TI  - Effects of glycosaminoglycans on the development of in vitro-matured and 
      fertilized porcine oocytes to the blastocyst stage in vitro.
AB  - We examined the effects of four glycosaminoglycans (GAGs) on the development of
      in vitro-matured (IVM) and -fertilized (IVF) porcine oocytes to the blastocyst
      stage. IVM and IVF oocytes were cultured in Whitten's medium supplemented with
      hyaluronic acid, chondroitin sulfate A, dermatan sulfate, or heparin at 38.5
      degrees C in an atmosphere of 5% CO2 in humidified air for up to 6 days. After 2
      days in culture, 28-34% of the inseminated oocytes cleaved to the 2- to 8-cell
      stage, and the GAGs showed no significant effect on development. After 6 days in
      culture, blastocysts were observed in all groups. The percentage of blastocysts
      was significantly higher in hyaluronic acid-supplemented medium (14%) than in
      dermatan sulfate-supplemented (5%), heparin-supplemented (2%), or nonsupplemented
      (2%) media. In addition, the percentage of blastocysts was significantly higher
      in chondroitin sulfate A-supplemented medium (11%) than in heparin-supplemented
      and nonsupplemented media, although the number of blastocysts in chondroitin
      sulfate A was not significantly different from that in hyaluronic acid- and
      dermatan sulfate-supplemented media. There were no significant differences in the
      mean number of nuclei per blastocyst cultured in any group. The effects of
      hyaluronic acid and chondroitin sulfate A on development to the blastocyst stage
      was examined at various concentrations. After 6 days in culture, development of
      IVM and IVF oocytes to the blastocyst stage was best supported in 0.5 mg/ml
      hyaluronic acid-supplemented (17%) and in 0.1 or 0.5 mg/ml chondroitin sulfate A
      supplemented (10% or 9%, respectively) media. It is concluded from these results
      that hyaluronic acid and chondroitin sulfate A supported the development of
      porcine oocytes matured and fertilized in vitro to the blastocyst stage.

PMID- 9603258
TI  - Gonadotropin-I and -II subunit gene expression of male striped bass (Morone
      saxatilis) after gonadotropin-releasing hormone analogue injection: quantitation
      using an optimized ribonuclease protection assay.
AB  - In fish, both gonadotropin (GtH)-I and -II are involved in the spermatogenic
      process, but the differential regulation of these hormones by GnRH is still
      poorly understood. To gain further insight into the GnRH regulation of GtH-I and 
      II gene expression in the male striped bass, we have developed and optimized a
      ribonuclease protection assay for the simultaneous measurement of all GtH subunit
      mRNAs in a single pituitary gland. The RNA extraction protocol enables the
      determination of GtH protein content in the same sample, thus enhancing the power
      of the method. Maturing striped bass males were injected intramuscularly with [D
      Ala6,Pro9Net]-LHRH (GnRHa) and sampled at 6 and 24 h postinjection. The mRNA
      levels of the alpha subunit and GtH-IIbeta increased after 6 h (4- and 6-fold,
      respectively), while the GtH-Ibeta mRNA levels increased only 2-fold after 24 h.
      Interestingly, GnRHa stimulation caused a significant increase in beta-actin mRNA
      levels. GnRHa treatment also resulted in a 2-fold decrease in pituitary GtH-II
      content, associated with a dramatic increase of plasma GtH-II levels from
      undetectable levels (< 0.2 ng/ml) to 13+/-2 ng/ml after 6 h. These results
      demonstrate that both GtH-Ibeta and -Ilbeta are expressed during striped bass
      spermatogenesis and that the two genes are subjected to differential regulation
      by GnRHa.

PMID- 9603259
TI  - Characteristics of prolonged dominant versus control follicles: follicle cell
      numbers, steroidogenic capabilities, and messenger ribonucleic acid for
      steroidogenic enzymes.
AB  - Cattle with low (subluteal) levels of plasma progesterone develop a persistent
      dominant follicle; plasma estradiol and LH pulse frequency are elevated, and
      fertility subsequent to the ovulation of a prolonged dominant follicle is
      compromised. The hypotheses were 1) that prolonged dominant follicles produce
      more estradiol because they have theca and granulosa cells with an enhanced
      capacity to produce androgen and estradiol, respectively, and 2) that these
      changes in steroidogenic capacity are paralleled by concomitant changes in mRNA
      for the appropriate steroidogenic enzymes. Prolonged dominant follicles were
      induced by treating Holstein heifers with exogenous progesterone via an
      intravaginal controlled internal drug-release device (CIDR) from Day 14 to 28 of
      the cycle. Prolonged dominant follicles were collected just before (CIDRb, Day
      28; n=4) or 24 h after (CIDRa, Day 29; n=4) CIDR removal, and their steroidogenic
      capacity was compared to that of growing, control dominant follicles obtained
      just before (CONTb, n=4) or 24 h after (CONTa, n=4) a luteolytic injection of
      prostaglandin F2alpha during the late luteal phase. After natural luteolysis,
      CIDR heifers maintained subluteal concentrations of progesterone (1-2 ng/ml) and
      had higher estradiol and LH pulse frequency than control heifers, as expected. In
      CIDR heifers, prolonged dominant follicles were present on the ovary for a longer
      time, reached a larger diameter, and had more granulosa cells and a larger mass
      of theca than dominant follicles from control heifers (p < 0.05). Concentrations
      of steroids in follicular fluid, estradiol secretion by granulosa cells in vitro,
      and levels of mRNA for steroidogenic enzymes in theca and granulosa cells
      provided no evidence for greater capacity of theca and granulosa cells of CIDR
      follicles to produce androgen and estradiol. In fact, follicular fluid estradiol
      and mRNA for P450 aromatase were higher after luteolysis than before in control
      animals (p < 0.05) but not after CIDR removal in treated animals. Therefore, the
      data do not support the hypotheses. Rather it is suggested that prolonged
      dominant follicles produce more estradiol because they have more granulosa cells
      and a larger mass of theca than control dominant follicles. In contrast,
      progesterone concentrations in the follicular fluid increased in CIDRa relative
      to CIDRb follicles (p < 0.05), a change that did not occur in control follicles;
      and granulosa cells from CIDRa follicles secreted more progesterone than
      granulosa cells from any other group. The increased capacity of CIDRa follicles
      to secrete progesterone suggests premature luteinization, which could contribute
      to decreased fertility in cattle that ovulate a prolonged dominant follicle.

PMID- 9603260
TI  - Autonomous cell death of mouse male germ cells during fetal and postnatal period.
AB  - Germ cell degeneration is common in mammalian testes during the developmental as
      well as the adult period. To investigate the extent and mechanisms of male germ
      cell death during fetal and neonatal life, the testes of mice at various fetal
      and postnatal ages extending from 13 days of gestation to 7 wk after birth were
      examined by electron microscopy and/or terminal deoxynucleotidyl transferase
      mediated dUTP nick end-labeling (TUNEL). Electron microscopy revealed that the
      number of cells with typical features of spermatogenic cell apoptosis was highest
      at 13 days of gestation, coinciding with the time of immigration of primordial
      germ cells into gonads. A second peak was observed around 10-13 days after birth
      when the first wave of spermatogenesis had started and active spermatogonial
      proliferation was present. Surprisingly, we found a significant number of dying
      cells around birth, which exhibited morphological features of necrotic death. In
      agreement with the results of electron microscopy, TUNEL staining revealed that
      the dying germ cells present around birth were TUNEL negative, while positive
      nuclei were abundant in the lumen of seminiferous tubules of testes of 10- to 13
      day-old mice. To investigate the mechanisms of induction of germ cell death, we
      examined the expression of Fas antigen immunohistochemically using rabbit
      antiserum raised against synthetic peptides for part of mouse Fas antigen. We
      found that among various developmental stages investigated, positive
      immunostaining for Fas antigen was present between 17 days of gestation and 1 day
      after birth, with the most intensive staining occurring on 17 days of gestation.
      Therefore, Fas-induced pathways may be implicated in embryonic male germ cell
      death, not prepubertal spermatogenic cell death.

PMID- 9603261
TI  - Shedding of a rat epididymal sperm protein associated with infertility induced by
      ornidazole and alpha-chlorohydrin.
AB  - The protein composition of epididymal fluid and sperm extracts of rats treated
      with the nitroimidazole compound ornidazole was investigated by two-dimensional
      gel electrophoresis. Epididymal luminal fluid from the corpus and cauda regions
      of male animals rendered infertile by ornidazole treatment contained a prominent
      protein (contraception-associated protein 1, CAP1) with a molecular mass of
      approximately 25 kDa and an isoelectric point (pI) of 5.8; it was not found in
      fluids, but was present in sperm, from fertile vehicle-fed rats. Infrared matrix
      assisted laser desorption/ionization mass spectrometry indicated that the
      molecular mass of CAP1 was 20420+/-120 daltons. Analysis of 17 amino acids
      demonstrated 49% homology to a diuretic hormone from an insect (Acheta
      domesticus). Densitometric quantitation of CAP1 on silver-stained gels indicated
      its presence in greater amounts in cauda than in corpus fluid from treated
      animals, whereas fluid from the rete testis lacked CAP1. In vitro incubations of
      tissue from the caput, corpus, and cauda epididymidal regions with
      [35S]methionine gave no hint that CAP1 was a secretion product of the epididymal
      epithelium. The absence of CAP1 from luminal fluid obtained from the sperm
      depleted corpus epididymidis of efferent duct-ligated ornidazole-fed rats
      suggested a spermatozoal origin. CAP1 was present in spermatozoa from the caput
      epididymidis but not from the rete testis in control animals. Less CAP1 was
      present in detergent extracts of cauda sperm from ornidazole-treated rats than in
      sperm from control animals, suggesting a contraceptive-related displacement of
      protein from sperm to fluid. The association of ornidazole- and alpha
      chlorohydrin-induced infertility with the presence of CAP1 in epididymal fluid,
      probably originating from spermatozoa, suggests a critical role for this protein
      in fertilization.

PMID- 9603262
TI  - Effects of interleukin (IL)-6 on luteinizing hormone- and IL-1beta-induced
      ovulation and steroidogenesis in the rat ovary.
AB  - Evidence that cytokines have important roles in ovulation is accumulating, with
      various cytokines having been found to influence the ovulatory cascade.
      Interleukin (IL)-6 is a pluripotent cytokine involved in inflammatory reactions,
      and it has been demonstrated in high concentrations in human ovarian follicular
      fluid and in vitro in secretions from the ovary. We set out to determine the
      effect this cytokine has on ovulation rate and steroidogenesis in the in vitro
      perfused rat ovary. Preovulatory ovaries were taken from eCG-primed animals, and
      ovulation was induced by LH (100 ng/ml) alone or in combination with cytokine.
      Ovaries in the IL-6/LH groups (IL-6 concentration of 0.19 nM or 1.9 nM) did not
      have ovulation rates different from ovaries in the LH-only group. Ovaries in the
      LH/IL-1beta group ovulated more oocytes than ovaries in the LH-only group (LH/IL
      1beta =11+/-1.8 oocytes; LH alone=4.9+/-1.1; p=0.015) and the IL-6/LH/IL-1beta
      group (LH/IL-1beta/IL-6 [0.19 nM]=4+/-1.40; LH/IL-1beta=11+/-1.8; p=0.009). We
      have found that 1) exogenous IL-6 did not significantly alter the LH-induced
      ovulation rate but significantly reduced the LH/IL-1beta-induced ovulation rate;
      2) exogenous IL-6 did not alter LH-induced progesterone levels measured at time
      points during the perfusion period, but the average increase in progesterone over
      basal level was stimulated by IL-6; 3) exogenous IL-6 did not affect LH-induced
      estradiol production; 4) exogenous IL-6 did not affect LH-induced androstenedione
      production but increased LH/IL-1beta-induced production; 5) exogenous IL-6 did
      not affect LH-induced prostaglandin E2 production. This study demonstrates that
      IL-6 does not play a role in regulating ovulation induced by LH in vitro but is
      capable of reducing LH/IL-1beta-enhanced ovulation rates. In addition, IL-6 may
      play a role in the regulation of ovarian steroid production.

PMID- 9603263
TI  - Expression pattern of phospholipid hydroperoxide glutathione peroxidase messenger
      ribonucleic acid in mouse testis.
AB  - To determine the expression pattern of phospholipid hydroperoxide glutathione
      peroxidase (PHGPx) mRNA in testes, Northern (3-, 8-, 40-, and 80-wk-old mice) and
      in situ (8-wk-old mice) hybridization analyses using digoxigenin-labeled RNA
      probes for PHGPx were performed in the testes of ICR mice. PHGPx mRNA in the
      mouse testes was first expressed at 3 wk of age, greatly increased at 8 wk, and
      persisted at the high level until 80 wk. According to in situ analysis, the PHGPx
      mRNA was expressed stage-specifically during spermatogenesis. It first appeared
      in pachytene spermatocytes of stage X, gradually increased in round spermatids
      during early spermiogenesis, and reached a peak in step 10-11 elongating
      spermatids. After step 12, PHGPx mRNA began to show a progressive decline in the
      spermatids and was weakly detected in step 16 spermatids. However, the signal was
      not detected in spermatogonia or early spermatocytes. On the other hand,
      according to in situ and reverse transcription-polymerase chain reaction
      analyses, PHGPx mRNA was also expressed in Leydig cells. These findings suggest
      that PHGPx in testes may be closely involved in spermatogenesis as well as having
      a general antioxidant function.

PMID- 9603264
TI  - Spatio-temporal pattern for expression of galectin-3 in the murine utero
      placental complex: evidence for differential regulation.
AB  - In mice, immunoreactive galectin-3 protein has previously been localized in
      uterine epithelial cells adjacent to implanting blastocysts as well as in the
      decidualized endometrium of implantation sites, uterine natural killer cells, and
      several types of placental trophoblast cells. Because galectin-3 is a soluble
      extracellular molecule, protein localization by immunohistochemical methods does
      not demonstrate its cellular origin. Therefore, the present study was undertaken
      to determine precisely which cell types in the utero-placental complex express
      galectin-3 mRNA. In situ hybridization results demonstrated that galectin-3 mRNA
      was expressed throughout the utero-placental complex in all cell types previously
      shown to contain immunoreactive protein, including uterine epithelium,
      decidualized endometrium, uterine natural killer cells, and placental
      trophoblasts. These results indicate that galectin-3 protein is not synthesized
      in a restricted cell type and translocated through the extracellular spaces to
      other tissue compartments. Furthermore, Northern blot analysis of total RNA
      prepared from separated fetal and maternal components of utero-placental
      complexes demonstrated different patterns of expression for galectin-3 mRNA in
      the uterus and placenta. Relative levels of galectin-3 mRNA peak at midgestation
      in the implantation site and during the second half of gestation remain elevated
      in the placenta but decline in the uterus. Separate mechanisms for regulating
      expression of galectin-3 on opposite sides of the feto-maternal interface are
      indicated.

PMID- 9603265
TI  - Expression of G1 cyclins and cyclin-dependent kinase-2 activity during terminal
      differentiation of cultured human trophoblast.
AB  - Cyclin-dependent kinases (Cdks) and their cyclin partners regulate mammalian cell
      proliferation and withdrawal from the cell cycle and, as such, control
      differentiation in many tissues. Studies were undertaken to examine the roles of
      cell cycle proteins in differentiating cytotrophoblasts. Cyclin E gene and
      protein expression was down-regulated after 24 h in cultured trophoblasts. Cdk2
      associated kinase activity was decreased after 96 h in culture as was the amount
      of cyclin E in complexes with Cdk2; however, levels of the Cdk inhibitor,
      p27Kip1, were significantly increased. In freshly isolated trophoblasts and in 24
      h cultures, the retinoblastoma gene product (pRb) was found in both the active
      and inactive forms, yet only hypophosphorylated, active pRb was present in
      syncytiotrophoblast. Thus, inactivation of Cdk2 through cyclin E down-regulation
      and increased p27Kip1 expression leads to an accumulation of active pRb in
      syncytiotrophoblast. Prevention of entry into S phase by hypophosphorylated pRb
      may allow trophoblasts to respond to signals that potentiate differentiation. Our
      studies suggest that regulation of G1-phase Cdk activity may be involved in the
      terminal differentiation process of cytotrophoblasts.

PMID- 9603266
TI  - Developmental expression and localization of the prolactin receptor (PRL-R) gene
      in ewe mammary gland during pregnancy and lactation: estimation of the ratio of
      the two forms of PRL-R messenger ribonucleic acid.
AB  - In this study, we have analyzed the developmental expression of the prolactin
      receptor (PRL-R) gene in the ewe mammary gland during pregnancy and lactation.
      Using Northern and slot-blot analysis and in situ hybridization, we showed that
      the level of PRL-R mRNA in mammary epithelial cells increased during the second
      half of pregnancy, decreased at the end of pregnancy, and remained relatively
      stable during lactation with a level above that observed at the beginning of
      pregnancy. As shown by RNase protection assay, the ratio of the long to the short
      form of the PRL-R mRNA was always above 1. This ratio increased between Day 70 of
      pregnancy and term and decreased progressively during lactation. The high level
      of PRL-R mRNA before the induction of alphaS1-casein gene expression suggests
      that PRL may be involved in the growth and development of the mammary gland. More
      precisely, the increase of the ratio of the long to the short form of the PRL-R
      during lactogenesis suggests that the latter form may have a dominant negative
      action in the activation of milk protein gene transcription. Thus the long/short
      form ratio of the PRL-R may play a key role in the shift between growth and
      differentiation of the mammary gland.

PMID- 9603267
TI  - Meiosis-activating sterol promotes resumption of meiosis in mouse oocytes
      cultured in vitro in contrast to related oxysterols.
AB  - The sterol 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol (FF-MAS
      [follicular-fluid meiosis-activating sterol]) from human follicular fluid has
      recently been identified as a compound that induces the resumption of meiosis. FF
      MAS and various oxysterols have been reported to transactivate the orphan
      receptor LXRalpha. The objective was to determine the biological activity of
      synthetic FF-MAS on the resumption of meiosis and final maturation of mouse
      oocytes in vitro. In order to evaluate whether LXRalpha might mediate FF-MAS
      action on the oocyte, we compared the capability of various compounds to activate
      LXRalpha-dependent transcription and to induce resumption of meiosis in the
      oocyte assay. Ovaries were isolated from immature mice primed with FSH 48 h
      before collection. Naked oocytes (NkO) and cumulus enclosed oocytes (CEO) were
      isolated from follicles. The oocytes were cultured in two groups, NkO and CEO,
      respectively, in media containing either 3 mM hypoxanthine, 5 microM IBMX, or
      0.100 mM dbcAMP to maintain the oocytes in the germinal vesicle stage. The
      resumption of meiosis was assessed by the frequency of germinal vesicle breakdown
      (GVBD) after 24 h of in vitro culture. FF-MAS overcame the meiotic inhibition by
      hypoxanthine in both the NkO group and CEO group in a dose-dependent manner
      within the concentration range 0.07-7 microM. FF-MAS displayed similar potency in
      all inhibitory agents used. Also, FF-MAS significantly increased the formation of
      polar bodies in both the CEO and NkO group. The oxysterols 22(R)
      hydroxycholesterol (a potent ligand for the LXRalpha receptor), 16
      hydroxycholesterol, 25-hydroxycholesterol, and 27-hydroxycholesterol, as well as
      cholesterol, were tested without any significant effect on maturation compared to
      that of controls. Oxysterols and FF-MAS were observed to activate LXRalpha. In
      conclusion, the results reported here clearly demonstrate that synthetic FF-MAS
      exclusively is capable of mediating resumption of meiosis in vitro in both NkO
      and CEO irrespective of the inhibitory substance used. In contrast, the
      oxysterols and cholesterol had no significant biological activity on this oocyte
      function, and consequently we found no correlation between LXRalpha activation
      and meiosis stimulation.

PMID- 9603268
TI  - Autocrine mediators are required to act on the embryo by the 2-cell stage to
      promote normal development and survival of mouse preimplantation embryos in
      vitro.
AB  - Autocrine mediators released by the early embryo are implicated in the support of
      embryo development. Their mechanisms and timing of action, however, are
      uncertain. This study shows that their action is necessary during the 2-cell
      stage of development, at which time they do not act as classical growth factors,
      having no impact on the rate of cell-cycle progression. Rather, they act as
      survival factors, protecting embryos from subsequent cell death. Culture of
      zygotes for the first 48 h after insemination (but not the first 24 h only) at a
      high concentration of 1 embryo/microl before transfer to a concentration of 1
      embryo/100 microl significantly improved development compared with culture at the
      lower concentration for 120 h. By contrast, if the initial 48 h of culture was at
      1 embryo/100 microl, subsequent culture at 1 embryo/microl caused no improvement.
      Platelet-activating factor (PAF) supplementation (0.186 microM) of media for the
      48-h period after insemination (but not 24 h only) improved the development of
      embryos cultured at low embryo concentrations (1 embryo/10 microl) even when
      transferred to PAF-free media for the subsequent 72-h culture period. The ability
      of PAF to mimic the effects of higher embryo density implicates embryo-derived
      PAF as one of the autocrine mediators stimulating early embryo development. The
      cell death that occurred at low embryo concentration had a mixed phenotype: some
      cells had lost membrane integrity whereas others had intact membranes but
      punctate or fragmented chromatin. It is concluded that the action of autocrine
      diffusible factors, including PAF, are necessary during the 2-cell stage for
      subsequent survival and normal development of embryos to the blastocyst stage.

PMID- 9603269
TI  - Synergistic effects of prostaglandin F2alpha and tumor necrosis factor to induce
      luteolysis in the pig.
AB  - There is ample evidence that prostaglandin F2alpha (PGF2alpha) is a luteolytic
      substance in sows, however, there is also some evidence that it may stimulate
      progesterone (P4) secretion in young corpora lutea (CL). In vitro studies also
      suggested that tumor necrosis factor alpha (TNF) is inhibitory to luteal cell P4
      and estradiol-17beta (E2) release. Since E2 is a strong luteotropic substance in
      porcine CL, we studied the effects of intraluteal application of PGF2alpha and
      TNF alone and in combination on the secretion of P4 and E2 in freely moving sows.
      Furthermore, the effects of intraluteal infusion of E2 and its stereoisomer,
      estradiol-17alpha, on luteal function, were also determined. Microdialysis
      systems were implanted into CL at Day 10 of the estrous cycle. After a 24-h
      recovery period, PGF2alpha (10(-6) M) or E2 (10(-6) M) was applied daily for 6 h
      into the CL. PGF2alpha caused a stimulation of E2 and P4, and E2 also stimulated
      P4 secretion at Days 11 and 12, but the stimulatory effect of both substances
      diminished as the CL approached luteolysis. Intraluteal TNF application resulted
      in a transient increase of P4 secretion, which was followed by a dramatic
      reduction of P4 release. When TNF-pretreated CL were exposed to PGF2alpha at Day
      11 of the estrous cycle, the prostaglandin was no longer able to stimulate but
      rather inhibited E2 and P4 secretion. Intraluteal application of estradiol
      17alpha had no effect on P4 secretion. These results are suggestive that the
      PGF2alpha-induced E2 secretion in young and middle-aged CL is stimulatory to P4
      secretion. Under the influence of macrophage-derived TNF production, E2 secretion
      is inhibited, and thereby PGF2alpha and TNF cause functional luteolysis.

PMID- 9603271
TI  - Generation of transgenic porcine chimeras using primordial germ cell-derived
      colonies.
AB  - In mice, two pluripotent cell lines, embryonic stem (ES) cells and embryonic germ
      (EG) cells, have been identified. We present here results indicating that porcine
      EG cell lines can be isolated, genetically transformed, and utilized to make
      transgenic chimeras. Briefly, primordial germ cells (PGCs) were isolated from Day
      25-27 fetuses and plated on STO feeder cells in Dulbecco's modified Eagle's
      medium:Ham's F-10 medium supplemented with 0.01 mM nonessential amino acids, 2 mM
      glutamine, 15% fetal bovine serum, 0.1 mM 2-mercaptoethanol, 40 ng/ml human stem
      cell factor, 20 ng/ml human basic fibroblast growth factor, and 20 ng/ml human
      leukemia inhibitory factor. For genetic transformation, cells were electroporated
      with a construct containing the green fluorescent protein under control of the
      cytomegalovirus promoter. After electroporation, cells were plated and later
      examined under fluorescein isothiocyanate excitation. Fluorescent colonies were
      selected for chimera generation. Blastocysts collected from gilts on Day 5 were
      injected with 10-15 transgenic PGC-derived cells and transferred into recipient
      gilts. Gilts were hysterectomized on Day 25, and fetal tissues were analyzed by
      Southern blotting. Three chimeras out of 20 fetuses analyzed were transgenic.
      Additionally, when one recipient gilt was allowed to go to term, one piglet with
      transgenic contribution was identified.

PMID- 9603270
TI  - Maturation in vitro of pig oocytes in protein-free culture media: fertilization
      and subsequent embryo development in vitro.
AB  - In the present study, attempts were made to develop a protein-free (PF) in vitro
      maturation (IVM) system for pig oocytes and to examine subsequent embryo
      development after in vitro fertilization. In experiment 1, four IVM media were
      tested: 1) control: North Carolina State University (NCSU) 23+10% porcine
      follicular fluid; 2) PF-NCSU: NCSU 23+0.1% polyvinyl alcohol (PVA)+1% amino
      acids; 3) PF-TCM: Tissue culture medium (TCM) 199+PVA; and 4) PF-WM: PF-Waymouth
      MB 752/1 medium (WM)+PVA. Oocytes were cultured in the respective media
      containing eCG and hCG (10 IU/ml each) for 20-22 h and then without hormonal
      supplements for an additional 20-22 h. After culture, the degree of cumulus
      expansion and frequency of nuclear maturation were determined. Some oocytes were
      coincubated with frozen-thawed spermatozoa for 5-6 h in modified Tris-buffered
      medium containing caffeine and BSA. In experiment 2, oocytes were matured in
      control, PF-TCM, and PF-WM, fertilized in vitro, and cultured for 144 h in NSCU
      23+BSA. Fewer (p < 0.01) oocytes reached metaphase II stage in PF-NCSU (45% vs.
      80-85%) than in the other media. Oocytes matured in control medium showed the
      most cumulus expansion, followed by those in PF-TCM and PF-WM; those in PF-NCSU
      showed very slight expansion. A lower (p < 0.05) penetration rate was obtained
      for oocytes matured in PF-NCSU than in the control medium (59% vs. 81%). In
      contrast to those in control (96%) and PF-TCM (93%), oocytes in PF-WM (65%)
      showed a lower male pronuclear formation. Compared to that in the control, a
      significantly lower (p < 0.05) cleavage rate was also observed for oocytes
      matured in PF-WM. Similar proportions of embryos developed to the blastocyst
      stage when oocytes were matured in control (22%) and PF-TCM (13%). These results
      indicate that pig oocytes can be successfully matured in a protein-free medium
      with subsequent development to the blastocyst stage.

PMID- 9603272
TI  - Who drops out of drug-user treatment research on women?
AB  - Attrition or dropping out is an important methodological issue in drug-user
      treatment research. The purpose of this study was to describe and explain the
      degree of subject attrition-more specifically, postinclusion attrition-within the
      context of a research demonstration project which focused on a women's sensitive
      approach to drug-user treatment. Demographic variables, psychosocial outcome
      measures, and two treatment variables were examined as possible predictors of
      attrition from research participation. Findings showed attrition rates increased
      from admission, peaked at 3-month follow-up, and then declined substantially by
      the 12-month follow-up period. A logistic regression analysis showed only
      treatment discharge status to significantly predict subject attrition.

PMID- 9603273
TI  - Cultural identification and substance use in North America--an annotated
      bibliography.
AB  - Level of identification with one's culture has long been thought to be a
      predictor of substance use among ethnic minority populations. However, cultural
      identification is a complex construct that has been difficult to capture in a
      coherent theoretical way. Additionally, the various theoretical approaches have
      led to numerous and divergent methods of measurement. Although measurement is
      becoming more sophisticated, the evidence for a link between cultural
      identification and drug use remains elusive. There is evidence that immigrants to
      a new culture do change their pattern of substance use to match that of the host
      culture, but the mechanism of that change is not well understood. That culture
      impacts behavior is without question although how culture operates specifically
      with respect to substance use will require further effort.

PMID- 9603274
TI  - Primary socialization theory. The role played by personal traits in the etiology
      of drug use and deviance. II.
AB  - Primary socialization theory proposes that drug use and deviant behaviors emerge
      from interactions with the primary socialization sources--the family, the school,
      and peer clusters. The theory further postulates that the individual's personal
      characteristics and personality traits do not directly relate to drug use and
      deviance, but, in nearly all cases, influence those outcomes only when they
      affect the interactions between the individual and the primary socialization
      sources. Interpretation of research results from the point of view of primary
      socialization theory suggests the following: 1) Characteristics such as
      depression, anxiety, and low self-esteem are related to drug use and deviance
      only when they have strong effects on the primary socialization process, i.e.,
      among younger children; 2) Traits such as anger, aggression, and sensation
      seeking are related to drug use and deviance because these traits are more likely
      to influence the primary socialization process at all ages; 3) The
      psychopathologies that are least likely to interfere with bonding with prosocial
      socialization sources, the anxieties and most of the affective disorders, are
      less likely to have comorbidity drug dependence; and 4) Psychopathologies such as
      oppositional disorder, conduct disorder, attention deficit disorder, and
      antisocial personality are more likely to interfere with primary socialization,
      and the literature shows that these syndromes are also most likely to have a dual
      diagnosis with drug dependency.

PMID- 9603275
TI  - Patients' perceptions of chamba (marijuana) use in Malawi.
AB  - This study examines the perceptions of the social aspects, triggers, and effects
      of chamba (marijuana) use among psychiatric patients at Zomba Mental Hospital in
      Malawi. Focus groups were used to elicit responses from 44 male and 10 female
      psychiatric patients about their perceptions of chamba use in Malawi. This study
      provides insight into these patients' perceptions of the triggers and effects of
      their chamba use, and it has implications for the development of treatment and
      prevention programs for chamba users in Malawi.

PMID- 9603276
TI  - Analgesic use disorders among orthopedic and chronic pain patients at a
      rehabilitation clinic.
AB  - Interviews were conducted with 265 orthopedic and chronic pain patients, using a
      structured diagnostic instrument (ADDIS/SUDDS) concerning their use of
      analgesics. Twenty-two percent of the patients met criteria for analgesic use
      disorders in accordance with DSM-III-R; 18.5% fulfilled DSM-IV criteria.
      Dextropropoxyphene was the most common analgesic prescribed and was used by 47%
      of the patients who met criteria for analgesic use disorders. It is concluded
      that patients with chronic pain using narcotic analgesics are at considerable
      risk of developing analgesic use disorders. Assessment of the use of analgesics
      should be offered to pain patients taking narcotic drugs.

PMID- 9603277
TI  - Desire for help among drug-using Mexican-American arrestees.
AB  - In a sample of 88 drug-using Mexican-American arrestees, we examined demographic
      factors, drug-problem severity indicators, and personal and social resources as
      correlates of self-reported desire for help with problems related to drug use.
      Ethnicity-related attitudes, perceptions, and experiences were among the factors
      tested. Among 35 potential correlates in this dataset, recognition of drug
      related interpersonal problems was the sole significant correlate of desire for
      help in a multivariate regression analysis. This finding was interpreted in
      comparison to previously identified correlates of Mexican-American drug users'
      desire for help specifically in the form of drug user treatment. We derive
      implications regarding drug-use-associated problem recognition and other
      potential determinants of help-seeking and success in drug user treatment among
      Mexican-American drug users.

PMID- 9603278
TI  - HIV infection risks among homeless, mentally ill, chemical misusing men.
AB  - This study attempts to identify the specific role that each of three conditions
      afflicting homeless, mentally ill, chemically misusing (HMICM) men plays in
      exposing these men to the risk of HIV infection. Three hundred and fifteen HMICM
      men (33 of whom were HIV+) were interviewed on intravenous drug use (IVDU) and
      sex practices. Two scales of risky IVDU practices and sex conducts were
      constructed and analyzed in relation to HIV status. The severity of homelessness,
      mental illness, and chemical misuse, then, were analyzed as possible predictors
      of risky IVDU and sex practices. Strong correlations were found between IVDU
      practices and HIV seropositivity, and between risky sex conduct and HIV
      seropositivity. Serious depression was the strongest predictor of risky IVDU
      practices. Prolonged homelessness was the condition most associated with risky
      sexual conduct. This study concludes that HMICM men are at high risk for HIV
      infection, stemming, predominately, from two conditions: depression, leading to
      risky IVDU practices, and homelessness, leading to risky sex conduct with two
      separate types of risky behavior.

PMID- 9603279
TI  - Laser-activated solid protein bands for peripheral nerve repair: an in vivo
      study.

PMID- 9603280
TI  - Monte Carlo simulations for EndoBronchial Photodynamic Therapy: the influence of
      variations in optical and geometrical properties and of realistic and eccentric
      light sources.
AB  - BACKGROUND AND OBJECTIVE: Light dosimetry for endobronchial photodynamic therapy
      is not very advanced to date. This study investigates the dependency of the
      fluence rate distribution in the bronchial wall on several parameters. STUDY
      DESIGN/MATERIALS AND METHODS: A Monte Carlo model is employed for the
      illumination of a cylindrical cavity by a linear diffuser to compute the fluence
      rate distribution in the tissue. The influence of optical and geometrical
      properties (e.g., the absorption coefficient of the bronchial mucosa and the
      diameter of the treated lumen) have been investigated, as well as the
      consequences of varying output characteristics of the diffusers. The optical
      properties used are those of ex vivo pig bronchial mucosa. RESULTS: With on-axis
      linear diffusers that can be modelled as a row of isotropic point sources, a
      constant fluence rate buildup factor can be employed for varying diffuser lengths
      and lumen diameters. Extreme off-axis placement of the diffuser causes a highly
      variable, considerable increase in the maximum fluence rate as well as a highly
      asymmetrical fluence rate profile on the circumference of the illuminated lumen.
      The fluence rate profiles resulting from illumination with realistic diffusers
      can be evaluated by implementing the measured radiance profiles of these
      diffusers in the model. The changes in fluence rate caused by variations in the
      optical properties of the bronchial mucosa could be accounted for by diffusion
      theory. This relationship can be used to extrapolate the ex vivo results to the
      clinical situation. CONCLUSION: A set of practical rules of thumb is presented
      that can help to estimate fluence rate distributions in clinical practice.

PMID- 9603281
TI  - Quantitative changes in collagen levels following 830-nm diode laser welding.
AB  - BACKGROUND AND OBJECTIVE: The actual mechanism by which laser irradiation welds
      tissue is presently unknown; however, collagen is a major constituent of tissue
      welded by laser irradiation. STUDY DESIGN/MATERIALS AND METHODS: Collagen was
      extracted from the abdominal aorta of Wistar rats by acetic acid extraction and
      repeated pepsin digestion after tissue welding (254 W/cm2) by using an 830-nm
      diode laser. The collagen levels were determined by using the Sircol Collagen
      Assay (Biocolor, Northern Ireland). RESULTS: Compared with untreated aorta, the
      collagen content of the treated vessel was obvious decreased (P < 0.001)
      immediately after laser irradiation. Levels then increased by day 3, with a peak
      at day 10 (P < 0.002). The collagen content returned to normal levels on day 30
      and remained at this level throughout the rest of the experimental period.
      CONCLUSION: These results suggest that a proportion of the collagen molecules in
      the vessel are denatured by the heat of the laser. Collagen synthesis is
      stimulated during the healing process after laser welding with the parameters
      used in the present study.

PMID- 9603283
TI  - Treating bullous lung disease with Holmium YAG laser in conjunction with fibrin
      glue and DEXON mesh.
AB  - BACKGROUND AND OBJECTIVE: Holmium YAG (Ho:YAG) laser energy is highly absorbed by
      water, and this property is useful to uniformly ablate pulmonary bullae. The
      current study summarizes the data of a 39-month follow-up of patients treated for
      bullae with a Ho:YAG laser. STUDY DESIGN/MATERIALS AND METHODS: We used a Ho:YAG
      laser from August 1994 to April 1997 to treat small pulmonary bullae in 50
      patients. For the first five patients, Ho:YAG laser ablation was followed by
      resection for histological assessment. In the next six patients, fibrin glue was
      applied following bullae ablation with the Ho:YAG laser. In all subsequent
      patients, a DEXON, (polyglycolic acid) mesh patch soaked in fibrin glue was
      employed after ablation. RESULTS: From the six patients receiving only the fibrin
      glue following laser ablation, delayed pneumothorax developed in one patient. In
      the subsequent 39 patients patched with DEXON mesh soaked in fibrin glue, none
      encountered delayed pneumothorax. CONCLUSION: The combined use of fibrin glue and
      Dexon mesh with the Ho:YAG laser may be an effective technique for treating
      bullous lung disease.

PMID- 9603282
TI  - 780 nm low power diode laser irradiation stimulates proliferation of keratinocyte
      cultures: involvement of reactive oxygen species.
AB  - BACKGROUND AND OBJECTIVE: The purpose of this study was to determine irradiation
      parameters of a 780 nm low power CW diode laser (6.5 mW) leading to enhanced
      proliferation of cultured normal human keratinocytes (NHK). The possible role of
      reactive oxygen species (ROS) in this response was evaluated. STUDY
      DESIGN/MATERIALS AND METHODS: NHK were exposed to a single dose of 0 to 3.6 J/cm2
      (0-180 sec) of irradiation. Proliferation parameters studied were: incorporation
      of 3H-thymidine during 6-24 hr following irradiation; percentage of dividing
      cells and number of cells, 24 hr and 48 hr following irradiation, respectively.
      RESULTS: Proliferation of NHK exposed to 0.45-0.95 J/cm2 was significantly
      enhanced by 1.3-1.9-folds relative to sham-irradiated controls, as inferred from
      parameters studied. Exposure to other energy densities was considerably less
      effective in enhancing proliferation parameters. Added enzymatic antioxidants,
      superoxide dismutase or catalase, scavenging superoxide anions and H2O2,
      suppressed this enhanced proliferation. Added scavengers (alpha-tocopherol
      acetate, scavenging lipid peroxidation, or sodium azide, histidine, mannitol,
      scavenging singlet oxygen, superoxide anions, and hydroxyl radicals,
      respectively), or N-acetyl cysteine, the thiol-reducing agent, suppressed the
      response, but to different extents. CONCLUSIONS: The results indicate that 780 nm
      low power diode laser irradiation enhanced keratinocytes proliferation in vitro,
      with an apparent involvement of ROS in this response, and comparably, might be
      used to promote their proliferation in vivo to enhance wound healing.

PMID- 9603284
TI  - Minocycline-induced hyperpigmentation: treatment with the Q-switched Nd:YAG
      laser.
AB  - BACKGROUND AND OBJECTIVE: Cutaneous hyperpigmentations are well-documented, but
      nevertheless rare side-effects of high-dose or long-term minocycline therapy. The
      pigmental changes, may last for years, even though therapy has been abrogated. To
      date, no safe and effective therapy has been described to target this
      cosmetically disturbing sequela. STUDY DESIGN/MATERIALS AND METHODS: A 57-year
      old female patient with extensive pigmental changes of the face due to long-term
      minocycline therapy was treated in eight consecutive sessions with the Q-switched
      Nd:YAG-laser (1,064-nm wavelength, 5- to 7-nsec impulse length). RESULTS: A 90%
      resolution of the pigmentation could be achieved after five treatments. After the
      last session the lesions were completely gone; no hypopigmentation scars, or
      other side-effects were observed. CONCLUSION: Treatment with the Q-switched
      Nd:YAG laser seems to be an effective, safe, and easily applicable strategy for
      the therapy of minocycline-induced hyperpigmentations.

PMID- 9603285
TI  - Acute results, complications, and effect of lesion characteristics on outcome
      with the solid-state, pulsed-wave, mid-infrared laser angioplasty system: final
      multicenter registry report. Holmium:YAG Laser Multicenter Investigators.
AB  - BACKGROUND AND OBJECTIVE: The solid-state, mid-infrared holmium:YAG laser (2.1
      microm wavelength) is a relatively new percutaneous device that has recently been
      evaluated in a multicenter study. Because of its unique wavelength and
      photoacoustic effects on atherosclerotic plaques, this laser may be useful in
      treatment of symptomatic patients with coronary artery disease. This study sought
      to evaluate the safety and efficacy of mid-infrared laser angioplasty in the
      treatment of coronary artery lesions. PATIENTS AND METHODS: Laser angioplasty was
      performed on 2,038 atherosclerotic lesions in 1,862 consecutive patients with a
      mean age of 61 +/- 11 years. Clinical indications included unstable angina (69%),
      stable angina (20%), acute infarction (6%), and positive exercise test (5%).
      Complex lesion morphology included eccentricity (62%), thrombus (30%), total
      occlusion (27%), long lesions (14%), and saphenous vein grafts (11%). RESULTS:
      This laser catheter alone successfully reduced stenosis (>20%) in 87% of lesions.
      With adjunct balloon angioplasty, 93% procedural success was achieved. The
      presence of thrombus within the target lesion was a predictor of procedural
      success (OR = 2.0 [95% confidence interval 2.0, 4.0], P = .04). Bifurcation
      lesions (OR = 0.5 [95% confidence interval 0.2, 1.0], P = .05) and severe
      tortuosity of the treated vessel (OR = 0.4 [95% confidence interval 0.2, 0.9], P
      = .02) were identified as significant predictors of decreased laser success.
      Calcium within the lesion was associated with reduced procedural success (OR =
      0.57 [95% confidence interval 0.34, 0.97], P = .03), and calcified lesions
      required significantly more energy pulses than noncalcified lesions (119 +/- 91
      pulses vs. 101 +/- 86 pulses, respectively, P = .0002). Complications included in
      hospital bypass surgery 2.5%, Q-wave myocardial infarction 1.2%, and death 0.8%.
      Perforation occurred in 2.2% of patients; major dissection in 5.8% of patients,
      and spasm in 12% of patients. No predictor of major complications was identified.
      Six-month angiographic restenosis was documented in 54% of patients, and clinical
      restenosis occurred in 34% of patients. CONCLUSION: Mid-infrared laser has a
      safety profile similar to that of other debulking devices. This laser may be
      useful in select patients presenting with acute ischemic syndromes associated
      with intracoronary thrombus; however, like other coronary lasers, it is limited
      by the need for adjunctive balloon angioplasty and/or stenting to achieve
      adequate final luminal diameter. No beneficial effects on reducing 6-month
      restenosis rates were observed.

PMID- 9603286
TI  - Bubble formation as primary interaction mechanism in retinal laser exposure with
      200-ns laser pulses.
AB  - BACKGROUND AND OBJECTIVE: Retinal laser photocoagulation is generally performed
      by laser pulses of a few hundred milliseconds. The tissue interaction mechanism
      is a pure thermal interaction mechanism. As pulse duration gets shorter,
      different, non-thermal interaction mechanisms start to appear. The time domain
      for a change of tissue interaction mechanism seems to be in the ns and micros
      range. The goal of this study was to characterize the tissue interaction
      mechanism with 200-ns laser pulses, which approximate the thermal relaxation time
      of single melanin granules. MATERIALS AND METHODS: The retinas of 19 eyes of 10
      rabbits were irradiated by 10 and 500 repetitive laser pulses (wavelength, 532
      nm; repetition rate, 500 Hz; pulse duration, 200 ns; per pulse energy, 0-120
      microJ; retinal spot size, 100 microm). The effects were evaluated by fluorescein
      angiography, ophthalmoscopy and by theoretical thermal calculations. Light
      microscopy and transmission electron microscopy were additionally performed on
      lesions irradiated by 500 pulses. RESULTS: Single pulse threshold energies for
      angiographic visibility were 3.5 microJ (10 pulses) and 2.1 microJ (500 pulses),
      for ophthalmoscopic visibility 9.0 microJ (10 pulses) vs. 8.6 microJ (500
      pulses). At energy levels above ophthalmoscopic visibility macroscopically
      visible bubble formation inside the retina could be observed. This occurred at
      energy levels of 35 microJ (10 pulses) vs. 17 microJ (500 pulses). Microscopic
      evaluation of lesions irradiated with 500 pulses and energies at the angiographic
      threshold showed a damage primarily to the RPE. Additional outer segment damage
      of the photoreceptors could be found. A gap between damaged RPE cells and the
      outer segments could be repeatedly found as well as damaged RPE cells, which were
      detached from intact Bruch's membrane. Temperature calculation shows that
      temperatures above 100 degrees C may exist around single melanin granules.
      CONCLUSION: The studies suggest that RPE damage may occur by bubble formation
      around single melanin granules.

PMID- 9603287
TI  - Neurobiology of the regenerating retina and its functional reconnection with the
      brain by means of peripheral nerve transplants in adult rats.
AB  - Axotomy-induced degradation of retinal ganglion cells (RGC) can be delayed if the
      destructive features of activated microglial cells are pharmacologically
      neutralized, and prevented if the axons are permitted to regrow into transplanted
      autologous peripheral nerve (PN) pieces. Axotomized central nervous system
      neurons, whose regenerating axons are guided to their natural target areas in the
      brain with the aid of PN grafts, are capable of establishing synaptic contacts
      with normal morphological and electrophysiological properties. This study was
      undertaken to 1) morphometrically characterize and classify the regenerating rat
      RGC, 2) examine target-dependent effects on survival of subsets of neurons, and
      3) investigate whether reconnected neurons are capable of restoring visual
      functions. In analogy to the normal rat retina, as a first step, the retrogradely
      labeled, regenerating RGC were categorized into five classes which are
      morphologically distinct and reminiscent of normal RGC correlates (called types
      RI, RII, RIII, Rdelta-cells, and displaced RGC). It appeared that all types of
      ganglion cells contributed proportionally to regeneration of axons.
      Transplantation of a PN graft which was not reconnected with a central target
      (blind-ending group) and monitoring of the extant neurons showed a progressive
      disappearance of the regenerating RGC, such that 6 months after surgery
      predominantly few, large cells survived. When the retinas were treated with
      macrophage/microglia inhibiting factor (MIF), and the regenerating axons were
      guided into the pretectum, predominantly large RGC of type RI survived. Guidance
      of the axons into their major natural target, the superior colliculus (SC),
      resulted in selective survival of many small, RII-like RGC. Calculation of the
      dendritic coverage factors for the major types of RGC revealed that dendrites of
      the most abundant, small cells of type RII overlapped uniformly and covered the
      retinal surface completely, whereas cells of types RI and RIII did not suffice
      for surface coverage. The results of this first part of the work suggest that
      combined suppression of axotomy-induced microglial activation and guidance of
      regenerating axons with a PN graft into central targets is a suitable technique
      to produce sufficient numbers of regenerating axons which may retrieve some
      functional properties. Target-specific neuronal contacts are likely involved in
      morphological stabilization and better survival of regenerating neurons. The
      second goal of this study was to analyze the functional significance of the
      reestablished synaptic contacts made by regenerated retinocollicular neurons.
      Adult rats were trained in a T- or Y-maze to obtain a food reward with the aid of
      visual cues. One of their optic nerves was transected and the regenerating axons
      were guided into the optic tract with a PN graft, to enable them to reinnervate
      the SC and thalamus. Postoperative testing of the animals showed a drastic
      improvement of visual perception. The protocol of denervation of the SC (prior
      to, simultaneous with, or with a delay with respect to fiber arrival) determined
      the performance of the animals. Rats belonging to the first two groups performed
      almost as well as they had before the transplantation. The functional integrity
      of the retina was assessed by electroretinography, which revealed typical rod
      spectral sensitivity at 380 and 500 nm but reduced responsiveness to
      illumination. In accordance, neuroanatomical assessment of the functionally
      relevant RGC revealed intact morphologies and multiple synaptic contacts both
      within the retina and within the SC. Neuroanatomical tracing of small contingents
      of axons throughout the regenerative pathway revealed a rough retinotopic
      arrangement within the graft and the area of termination. Thus, animals could
      discriminate between simplified vertical versus horizontal stripes, and visual
      evoked potentials were positive after grafting. (ABSTRACT TRUNCATED)

PMID- 9603288
TI  - Distribution and regulation of the optic nerve head tissue PO2.
AB  - We investigated the distribution and regulation of the optic nerve head (ONH)
      tissue partial pressure of oxygen (PO2) under various stimuli and the role of the
      nitric oxide in the ONH circulation. Tissue PO2 was measured using double
      barreled recess microelectrodes in the intact eyes of miniature pigs during
      normoxia, hyperoxia, hypoxia, variations of systemic blood pressure, and after
      inhibition of the endothelial nitric oxide synthesis by the administration of
      nitro-L-arginine. Measurements were performed in front of the ONH at
      intervascular and juxta-arteriolar areas and at a depth of 50 and 200 microm
      within the ONH at the center and the rim. During normoxia, PO2 was
      heterogeneously distributed in the ONH, higher close to the arterioles than in
      intervascular areas. Hyperoxia induced a significant increase of juxta-arteriolar
      tissue PO2, while in intervascular areas no change was noticed. Hypoxia did not
      modify intervascular tissue PO2 at 200 microm depth within the ONH. Variations of
      the systemic blood pressure did not induce any significant change in ONH tissue
      PO2. Similarly, no modification was noticed after the administration of nitro-L
      arginine. There is a remarkable autoregulatory capacity of the ONH circulation
      that may compensate for parameters such as hyperoxia, hypoxia, and variations of
      the systemic blood pressure. Endothelially derived nitric oxide inhibition does
      not modify the ONH tissue PO2, probably because the tissue PO2 is stabilized by
      compensatory regulation.

PMID- 9603289
TI  - PMMA model of steep central islands induced by excimer laser photorefractive
      keratectomy.
AB  - We designed a polymethyl methacrylate (PMMA) model of refractive steep central
      islands (CIs) induced by PRK. A standardized photorefractive ablation procedure
      was performed using seven different excimer lasers on test PMMA specimens
      including 70 flat plates and 98 convex contact lenses. The resulting surface was
      analyzed by high-resolution confocal microscopy and computerized videokeratoscopy
      using both TMS-1 and CAS-2000 systems. A total of 50 (54.9%) CIs were observed
      using computerized videokeratoscopy. The rate of occurrence of CIs was
      significantly reduced by shock wave absorption (P = 0.0001), aspiration of fumes
      (P = 0.0044), and smaller diameter ablation (P = 0.0296). The diameter of the
      CIIs was significantly increased for broad-beam mode ablation (P = 0.016) and for
      larger ablation zones, (P = 0.042). The refractive power of CIs was significantly
      increased in the absence of a shock wave absorption system (P = 0.001). Only 20
      (40%) of the CIs detected by the TMS-1 device were identified on CAS-2000 at a
      0.5 diopter (D) scale resolution level. Shock wave induced deformation and
      subsequent dynamic alteration of convection forces applied to emitted particles
      may be the primary mechanism underlying the formation of CIs after PRK,
      regardless of any biological response of the ablated tissue. Reported rates and
      characteristics of CIs may largely depend upon the specific design of
      videokeratoscopes.

PMID- 9603290
TI  - Effects of topical adrenergic agents on tissue circulation in rabbit and human
      optic nerve head evaluated with laser speckle tissue circulation analyzer.
AB  - The effects of topical adrenergic agents on the tissue circulation of the optic
      nerve head (ONH) were studied in animal and human eyes with use of a laser
      speckle tissue circulation analyzer. Drugs studied were nipradilol, a beta1-2
      blocker with weak alpha-blocking and nitroglycerinlike activities; bunazosin, a
      selective alpha1-blocker; carteolol, a beta1-2-blocker with intrinsic
      sympathomimetic activity; and betaxolol, a selective beta1-blocker. In the animal
      experiment, one eye each of nine albino rabbits received 0.25% nipradilol (N = 9)
      twice daily for 15 days or 0.01% bunazosin (N = 10) twice daily for 20 days; the
      fellow eye received the vehicle of each drug in a randomized masked design.
      Normalized blur (NB) in an area of ONH free of visible surface vessels, a
      quantitative index of peripheral blood velocity in ONH, was measured under
      general anesthesia before treatment and 2 hours after the last instillation on
      the 15th or 20th day. At 15 days, intraocular pressure and NB in the nipradilol
      treated eyes decreased by 4.3 mm Hg (P < 0.01) and increased by 15.9% (P < 0.01),
      respectively, while those in the vehicle-treated eyes showed little change. At 20
      days NB in both bunazosin- and vehicle-treated eyes showed little change, while
      intraocular pressure decreased only in the bunazosin-treated eyes (P < 0.01). In
      the human volunteer experiment NB was averaged over five pulses (mean NB) in both
      eyes before and 1.5, 3.0 and 4.5 hours after a 30 microL instillation of the
      vehicle of carteolol or betaxolol to serve as a control. Intraocular pressure,
      blood pressure and pulse rate were also measured. One week later a 30 microL drop
      of 2.0% carteolol (N = 6) or 0.5% betaxolol (N = 10) was instilled in one
      randomly chosen eye and the vehicle for each drug in the other eye, and those
      parameters were measured as above in a double-masked manner. In the carteolol
      experiment, mean NB in both eyes was significantly higher at 3 hours than it was
      in the control experiment (P < 0.05), while intraocular pressure was
      significantly lower in both eyes and blood pressure and pulse rate showed little
      change. In the betaxolol experiment, intraocular pressure at 1.5 hours and blood
      pressure at 4.5 hours were significantly lower than those in the control
      experiment (P < 0.05), while mean NB and pulse rate showed little change. In
      summary, using the laser speckle method we found that topical nipradilol and
      carteolol increase ONH blood velocity in rabbits and humans, respectively. This
      finding suggests that some topical beta-blockers used clinically may influence
      the ONH tissue circulation in patients and that this method may be used in
      clinical situations to assess the effect of various drugs on ONH circulation.

PMID- 9603291
TI  - Clinical and morphological response to UV-B irradiation after excimer laser
      photorefractive keratectomy.
AB  - This paper represents an update on a study that has been reported elsewhere (Nagy
      ZZ et al: Ophthalmology 104:375-380, 1997). The aim of the study was to evaluate
      the clinical and light- and electron-microscopic effects of ultraviolet-B (UV-B)
      exposure on the outcome of photorefractive keratectomy (PRK). A total of 42
      pigmented rabbits were used in the study. One eye from each of 12 rabbits
      received a 193 nm 45-microm deep (-5.0 diopters [D]) excimer laser PRK, one eye
      from each of 12 rabbits received a 135-microm deep (-15.0 D) excimer laser PRK,
      and one eye from each of 12 rabbits received a 270 microm deep (-30.0 D) excimer
      laser PRK. Twenty-one days after PRK, six of the laser-treated eyes from each
      group were exposed to 100 mJ/cm2 UV-B (280-320 nm). The other six rabbits from
      the PRK groups received no further treatment. One eye from each of six rabbits
      received only UV-B irradiation, serving as control. Subepithelial haze was
      evaluated before and after UV-B irradiation. Clinical changes were followed by
      laser tyndallometry, confocal corneal biomicroscopy, ultrasound biomicroscopy,
      and endothelial specular microscopy. Corneal morphology was assessed 4, 8, and 12
      weeks after UV-B exposure, employing light microscopic and transmission electron
      microscopic techniques (TEM). Eyes only exposed to 100 mJ/cm2 UV-B exhibited
      keratitis for 2 days, but showed no haze and were histologically normal at all
      time intervals. The PRK-UV-B-irradiated rabbit eyes exhibited a significant
      increase of stromal haze compared to the eyes receiving PRK alone; this
      phenomenon correlated with the depth of photoablation. The severity of clinical
      findings also correlated with the previously attempted photoablation depth; in
      PRK-UV-B-irradiated eyes the symptoms were much more serious than in eyes treated
      with PRK alone. Histologically, the main difference between the UV-B-irradiated
      and nonirradiated-post-PRK eyes was the presence of anterior stromal
      extracellular vacuolization in the UV-B-exposed eyes. The vacuolated foci were
      confined to the PRK treatment area, contained increased numbers of keratocytes
      and showed a disorganization of normal collagen lamellae. Transmission electron
      microscopy revealed activated keratocytes containing abundant rough endoplasmic
      reticulum, prominent Golgi zones, and extracellular vacuoles filled with
      amorphous material. The haze and morphological changes showed a tendency to
      incomplete resolution over a period of 12 weeks. Ultraviolet-B exposure during
      post-PRK stromal healing exacerbates and prolongs clinical symptoms and the
      stromal healing response, which is manifest biomicroscopically by augmentation of
      subepithelial haze. The findings suggest that excessive ocular UV-B exposure
      should be avoided during the period of post-PRK stromal repair and that UV-B may
      modulate the response of tissues to excimer 193 nm, and perhaps, other laser
      energy in general.

PMID- 9603292
TI  - Temperature-controlled CO2 laser tissue welding of ocular tissues.
AB  - Lasers can be used for binding tissues by welding, but the clinical application
      of this method has been limited by the difficulties in defining and maintaining
      the optimal conditions. Fiberoptic radiometry allows accurate remote temperature
      measurements for control of laser tissue welding. We evaluated the use of a
      temperature-controlled tissue welding system to close corneal and corneoscleral
      wounds. Eighty ex vivo bovine eyes were used for the determination of welding
      parameters optimal for corneal wound closure. A 4 mm central corneal cut was
      closed with use of a CO2 laser (600 mw, 0.9 mm spot size), with tissue
      temperatures ranging from 45-70 degrees C and welding time ranging from 1-30
      seconds. Wound strength was measured as burst pressure of the sealed wound. The
      welding parameters found to cause the strongest wound binding were used to weld a
      limbal incision of 4 mm in 10 adult albino rabbits. The fellow eye of each animal
      was used as a control, and the same wound was closed with one 10/0 mersilen
      suture. Two animals were killed immediately after the procedure, and the eyes
      were sent for histologic examination. Eight rabbits were followed for 1 month.
      Clinical examination and refraction were done 1 day, 1 week, 2 weeks, and 1 month
      after the procedure. Corneal topographic evaluations were done 1 week after the
      procedure. After 1 month the animals were killed and the eyes were examined
      histologically. The optimal results of wound binding by laser welding in the
      enucleated bovine eyes were achieved with 55-60 degrees C and at a welding time
      of 12-20 seconds. At these parameters the burst pressure of corneal wounds was 70
      mm Hg. All laser-welded limbal wounds in the rabbits were tightly closed at the
      end of procedure and during the follow-up period. The refractive results after
      laser welding were equal to those of the controlled suture-closed wound. Laser
      tissue welding combined with tissue temperature monitoring can be used to close
      corneal wounds.

PMID- 9603293
TI  - The efficacy of cooling on excimer laser photorefractive keratectomy in the
      rabbit eye.
AB  - We cooled the surface of the cornea to reduce the thermal damage by the excimer
      laser ablation and referred to this method as "cooling photorefractive
      keratectomy" (cooling PRK). We performed conventional PRK and cooling PRK on
      rabbits' eyes and measured the thermal change during laser ablation. We also
      examined the degree of subepithelial haze and the tissues with a light microscope
      and an electron microscope. Normal corneal temperature of live rabbit corneas was
      about 32 degrees C and it rose to 41 degrees C after 300 laser shots. However,
      when we cooled the rabbit corneas to 24 degrees C with continuous irrigation of
      chilled BSS PLUS solution before laser ablation, the temperature rose only to 34
      degrees C after the same ablation. Slit-lamp evaluation showed that more severe
      corneal haze occurred with the conventional PRK procedure. At 2 weeks
      postoperatively, the mean haze score was 1.77 +/- 0.87 in the conventional PRK
      and 0.87 +/- 0.38 in the cooling PRK (P < 0.01). Light-microscopy examination
      showed epithelial hyperplasia and fibroblasts, type III collagen, and heat shock
      protein-70 in the subepithelium of corneas with conventional PRK procedure than
      with cooling PRK. Under the electron microscope, more disruption of the layers of
      fibroblasts and collagen fibrils was observed in the conventional PRK procedure
      than that of the cooling PRK. In conclusion, the cooling of the corneal surface
      in PRK effectively reduces tissue damage related to subepithelial haze and may
      enable us to reduce the degree of myopic regression.

PMID- 9603294
TI  - Ocular blood flow velocities in patients with proliferative diabetic retinopathy
      after panretinal photocoagulation.
AB  - Color Doppler imaging allows for simultaneous two-dimensional anatomical imaging
      and Doppler measurement of blood-flow velocity. Because hemodynamic changes have
      been seen in diabetic patients after photocoagulation by other techniques, the
      author compared 25 eyes of 25 patients with proliferative diabetic retinopathy
      before and 6 months and 1 year after panretinal photocoagulation with a matched
      control group of 30 eyes of 30 healthy volunteers. The ophthalmic artery, short
      posterior ciliary artery, central retinal vessels, and vortex veins of all
      patients were examined, and the systolic, diastolic, and mean arterial velocities
      were measured. Panretinal photocoagulation was performed with these parameters:
      800-1000 spots, 0.1 second, 500 microm argon laser. The blood velocity was
      significantly lower in diabetic patients than in normals in the ophthalmic artery
      and the central retinal artery. After treatment, blood-flow velocities were
      significantly lower than before photocoagulation in the ophthalmic artery, the
      central retinal artery and the central retinal vein. No statistically significant
      differences were found between 6 months and 1 year after panretinal
      photocoagulation. No significant correlations were found between age and blood
      velocities in diabetics and healthy volunteers. Eyes with proliferative diabetic
      retinopathy showed lower ocular perfusion velocities than normals in the
      ophthalmic artery and the central retinal artery. Photocoagulation resulted in a
      reduction in ocular blood-flow velocities in the ophthalmic artery, the central
      retinal artery and the central retinal vein; these values did not change
      significantly during 1 year of follow-up.

PMID- 9603295
TI  - Expression of c-fos and c-jun mRNA following transient retinal ischemia: an
      approach using ligation of the retinal central artery in the rat.
AB  - The expression of the proto-oncogenes c-fos and c-jun was examined by in situ
      hybridization at various timepoints following transient retinal ischemia by means
      of ligation of the retinal central artery in the rat. Ischemia of 90-minute
      duration resulted in the degeneration of neurons in both the ganglion cell layer
      and the inner nuclear layer at 48 hours after reperfusion. The expression of c
      fos and c-jun messenger RNA throughout the entire inner nuclear layer was
      transiently coinduced following 90-minute retinal ischemia with a peak at 1 hour
      after reperfusion. This expression was also found in the ganglion cell layer at 3
      hours after reperfusion. Weak signals for c-fos and c-jun mRNA were observed at
      24 hours after reperfusion and returned to near control levels by 48 hours. c-jun
      protein expression was detected in the ganglion cell layer, the middle of the
      inner nuclear layer, and optic nerve head at 3 hours, but not 1 hour, after
      lethal ischemia/reperfusion; however, c-fos protein expression was not detected
      after reperfusion. Whereas no neuronal degenerative changes were found at 7 days
      after 30-minute ischemic retina, c-fos and c-jun messenger RNA were also induced
      at 1 hour postreperfusion. To our knowledge, this study is the first report to
      show expression patterns of immediate-early genes after retinal
      ischemia/reperfusion. These results suggest that changes in expression of c-fos
      and c-jun after transient retinal ischemia are similar to those after transient
      brain ischemia, and the selective occlusion of the central retinal artery will
      provide a useful model for studying ischemic neuronal degeneration in vivo in the
      rat retina.

PMID- 9603296
TI  - Comparison between functional characteristics of healthy and pathological human
      retinal Muller glial cells.
AB  - Enzymatically isolated, noncultured Muller glial cells from human organ donor and
      patient eyes were studied using the whole-cell-voltage-clamp and the patch-clamp
      technique. The patients suffered mainly from choroidal melanomas, retinal
      detachment due to proliferative vitreorentinopathy, glaucomas, and perforating
      eye injuries. The organ donor eyes were used as a source of corneas for corneal
      transplantation. Use of the human retinal tissue was approved by the Ethics
      Committee of the School of Medicine, University of Leipzig. Most of the patient
      Muller cells showed a marked or complete loss of inwardly rectifying K+ currents,
      causing a dramatic increase in the input resistance. The zero current potential
      of the patient Muller cells, which is equivalent to the membrane potential, was
      significantly reduced (depolarized) as compared with the donor Muller cells. In
      contrast to the K+ current loss, the Na+ current density was significantly higher
      in patient Muller cells than in donor Muller cells; the number of Muller cells
      depicting Na+ currents increased from 33% (3 pA/pF) in donor Muller cells to 85%
      (about 12pA/pF) in patient Muller cells. Application of glutamate to the Muller
      cells generated a glutamate-transporter-mediated current, such as that seen in
      other species. A highly significant increase was noted for the high-affinity Na+
      dependent glutamate-transporter-current density in patient Muller cells compared
      with donor cells. The application of gamma-aminobutyric acid (GABA) evoked, in
      addition to the GABA transporter currents already known from Muller cells of
      other mammalian species, GABA(A)-receptor mediated currents in human Muller
      cells. We found that GABA(A) receptors are expressed in human Muller cells, but
      not in other nonprimate mammals. Whether a difference exists between the GABA(A)
      current density in donor and patient Muller cells remains to be seen. The results
      concerning the disappearance of K+ currents and diminution of the membrane
      potential may demonstrate early glial changes that may possibly precede
      pathological neuronal changes, at least in retinas from eyes with choroidal
      melanomas. In later stages of the diseases, the glial changes may be deleterious
      for the neurons, because they could diminish glutamate uptake due to the
      depolarized membrane potential. However, increased extracellular glutamate
      concentration is toxic for most neurons.

PMID- 9603297
TI  - The influence of intraocular pressure and systemic oxygen tension on the
      intravascular pO2 of the pig retina as measured with phosphorescence imaging.
AB  - The intravascular oxygen tension (pO2) of the pig retina was determined by
      measuring the phosphorescence lifetime of an intravenously injected dye.
      Pseudocolor images of the intravascular retinal pO2 were obtained. The method is
      noninvasive except for the application of the dye. The measurement system was
      adapted to a fundus camera. The systemic arterial oxygen pressure (PaO2) as well
      as the intraocular pressure (IOP) were altered. In the measurements the pO2 of
      the choriocapillaris was close to the systemic PaO2. Under normoxia, the retinal
      veins showed a lower pO2 of about 40 mm Hg. We found evidence of an
      autoregulation of the retinochoroidal pO2. The retina and the optic nerve head
      showed an autoregulation of the intravascular pO2 at low IOP, but were more
      sensitive to a moderate elevation of the IOP of about 40 mm Hg, as compared to
      the choroidal pO2. The pO2 of the choriocapillaris seemed to change little until
      the considerably high IOP value of about 50 mm Hg was attained. This behavior is
      due to either the high perfusion reserve capacity of the choroid or to
      autoregulation. Although our experiments refer to the perfusion of the pig eye,
      the results provide indirect evidence that even during a glaucoma attack the
      human choroid might be able to maintain a reasonable oxygen supply to the retina,
      whereas the intravascular pO2 of the retinal vessels and of the optic nerve head
      decrease strongly. The adaptation to a fundus camera facilitates a future
      clinical application if a nontoxic dye can be developed.

PMID- 9603298
TI  - Experimentally induced steroid cataract in the rat: a scanning electron
      microscopic study.
AB  - To clarify the histopathological changes of experimentally induced steroid
      cataract in Brown-Norway rat eyes, a scanning electron microscopic study was
      performed. The biomicroscopic appearance of the cataracts, which was quite
      similar to that of human eyes, was induced by daily application, either topically
      or systemically, of prednisolone acetate for 12 months. A single dose of 2 Gy X
      ray was given to the right eyes of all the animals 2 weeks before drug
      administration. Twenty-seven rats were divided into three groups: a control group
      (CTL), a group receiving topically administered prednisolone (TOP), and a group
      receiving systemically administered prednisolone (SYS). In vivo observation was
      performed through a slit-lamp microscope, and the lens findings were documented
      and objectively analyzed by an anterior eye segment analysis system over a period
      of 12 months. At the end of the 12-month period, X-ray-irradiated right eyes in
      the CTL group showed some minor lens changes on biomicroscopy, and non-X-ray
      irradiated left eyes were almost normal. In the TOP and SYS groups, either with
      or without X-ray irradiation, lenses showed anterior and posterior subcapsular
      opacification; however, the grade and increase of lens opacification were higher
      and faster in the eyes with X-ray irradiation. Scanning electron microscopic
      findings of the three groups at the 12th month were as follows. In the CTL group,
      the X-ray-irradiated right eyes showed minor changes. In the TOP group, the X-ray
      irradiated right eyes showed marked damage in the lens fibers of the anterior and
      posterior cortices, while the nonirradiated left eyes showed minor changes. In
      the SYS group, the X-ray-irradiated right eyes showed prominent cataractous
      disorganization of lens fibers in the shallow anterior and posterior cortices,
      and the non-X-ray-irradiated lenses were almost the same as those in the TOP
      group. These findings might suggest that even a minimum invasion of a low dose of
      X-ray irradiation plays a cocataractogenic or syncataractogenic role during the
      formation of steroid cataracts.

PMID- 9603299
TI  - Photorefractive keratectomy and cataract.
AB  - Fifty male albino rabbits were studied. Ten animals served as controls. Forty
      animals were prepared to receive photorefractive keratectomy (PRK), including
      anesthesia, scraping of the corneal epithelial cells, etc. Twenty of these
      animals then received PRK with energy delivered by excimer laser (pulse rate = 20
      Hz, fluence 250 mJ/cm2; number of pulses = 6032; cumulative UV dose = 1508J/cm2).
      The other 20 animals were exposed to the same operating microscope light as the
      PRK-treated animals, but they did not receive PRK. All three groups were divided
      into halves: the first half was immediately analyzed at 0 time, and the second
      half was observed 1 year later. Samples of aqueous humor and lens were analyzed.
      The levels of reduced and oxidized glutathione, hydrogen peroxide, ascorbic acid,
      and malondialdehyde were determined. Excimer laser-induced ultrastructural
      modifications of the lens, verified through scanning electron microscopy, were
      studied at the same intervals. Immediately after PRK, the biochemical parameters
      studied, both in aqueous humor and in lens of treated animals, showed significant
      differences. One year later, the observed biochemical variations in lens were
      still present, whereas aqueous humor values did not significantly differ from
      control values. Ultrastructural abnormalities of the lens appeared only 1 year
      after PRK In the animals that received only the preparation for PRK the
      biochemical and ultrastructural differences did not significantly vary as
      compared to the data obtained from control animals. These findings suggest that
      the biochemical and ultrastructural lens alterations induced by PRK may represent
      events relevant to cataractogenesis in the rabbit.

PMID- 9603300
TI  - Proceedings: International Workshop on Consumption Measures and Models for Use in
      Policy Development and Evaluation. Bethesda, Maryland, USA. May 12-14, 1997.

PMID- 9603301
TI  - Measuring quantity, frequency, and volume of drinking.

PMID- 9603302
TI  - Measuring drinking context.

PMID- 9603303
TI  - Cultural and subgroup issues in measuring consumption.

PMID- 9603304
TI  - Measuring lifetime drinking histories.

PMID- 9603305
TI  - Special issues of measurement in longitudinal studies.

PMID- 9603306
TI  - Modeling the distribution and consequences of alcohol consumption.

PMID- 9603307
TI  - Evaluating competing models of alcohol-related harm.

PMID- 9603308
TI  - Towards guidelines for low-risk drinking: quantifying the short- and long-term
      costs of hazardous alcohol consumption.

PMID- 9603309
TI  - Measuring drinking practices: how far we've come and how far we need to go.

PMID- 9603310
TI  - Virus-encoded proteinases of the Flaviviridae.

PMID- 9603311
TI  - The molecular biology of arteriviruses.

PMID- 9603312
TI  - Tracing the origins of louping ill virus by molecular phylogenetic analysis.
AB  - The nucleotide and deduced amino acid sequences of louping ill (LI) virus
      isolates, collected from representative regions of the British Isles and Norway,
      were determined for either the entire envelope gene (20 isolates) or for a
      portion of the envelope gene that spans a hypervariable region and includes an LI
      virus specific marker sequence (53 isolates). Phylogenetic analysis reveals the
      presence of three major geographical populations of LI virus in the British
      Isles, viz. Irish, Welsh and British LI viruses, which all cause
      encephalomyelitis in animals, predominantly sheep, and co-habit the same tick
      population. British LI virus occurs throughout Scotland, England, Ireland and
      Norway. Irish and Welsh LI viruses occur only in Ireland and Wales, respectively.
      Phylogenetic analysis also predicts that LI virus initially emerged in Ireland
      and that a descendant was introduced into Great Britain via Wales and was
      subsequently transported to the borders of Scotland, from where it was dispersed
      throughout Scotland, northern England and Norway. More recently, the British LI
      virus was reintroduced into Ireland and also into south-west England. Dates of
      lineage divergence, calculated from the synonymous substitution rate, indicate
      that LI virus emerged in the British Isles less than 800 years ago and most LI
      virus dispersal occurred during the last 300 years. By combining these data with
      historical records it appears that livestock movement can be implicated in the
      dispersal of LI virus.

PMID- 9603313
TI  - Immune response in pigs vaccinated with plasmid DNA encoding ORF5 of porcine
      reproductive and respiratory syndrome virus.
AB  - The ORF5-encoded major envelope glycoprotein (GP5) of porcine reproductive and
      respiratory syndrome virus (PRRSV) is one of the three major structural proteins
      of this virus. While some porcine convalescent sera and monoclonal antibodies
      directed against GP4 and GP5 have the capacity to neutralize the virus in vitro,
      the protein specificity of porcine neutralizing sera has not yet been
      established. DNA immunization with a plasmid encoding GP5 of PRRSV, under the
      control of a human cytomegalovirus promoter, induced anti-GP5-specific
      neutralizing antibodies in pigs and BALB/c mice. The GP5 protein specificity of
      neutralizing sera was confirmed by immunoblotting and ELISA. Peripheral blood
      mononuclear cells obtained from DNA-vaccinated pigs underwent blastogenic
      transformation in the presence of E. coli-expressed recombinant ORF5-encoded
      protein, indicating the specificity of the cellular immune response to GP5.
      Following a massive intratracheal challenge with the virulent IAF-Klop strain of
      PRRSV, DNA-vaccinated pigs were protected from generalized viraemia and the
      development of typical macroscopic lung lesions that were observed in
      unvaccinated, virus-challenged controls, as well as in pigs that were immunized
      with E. coli-expressed GST-ORF5 recombinant fusion protein. Interstitial
      pneumonitis and broncho-alveolitis were remarkably milder in DNA-vaccinated
      animals. These results suggest that the GP5 of PRRSV is a good candidate for a
      subunit recombinant-type vaccine.

PMID- 9603314
TI  - Attenuation of neurovirulence of Theiler's murine encephalomyelitis virus strain
      GDVII is not sufficient to establish persistence in the central nervous system.
AB  - Virus recombinants constructed from Theiler's murine encephalomyelitis virus
      (TMEV) strain GDVII, which causes a rapidly fatal encephalitis in mice, and the
      less virulent BeAn, which persists in the murine central nervous system (CNS) and
      causes inflammatory demyelination, and a GDVII mutant deleted of 46 of 76 leader
      protein amino acids were analysed for virus persistence in the CNS. The two
      recombinant and mutant viruses principally contain GDVII sequences including the
      nucleotides encoding the polyprotein and 3' untranslated region. These viruses
      were found to replicate in the CNS of mice but they did not produce acute
      encephalitis or paralysis, i.e. they were attenuated in neurovirulence compared
      to the GDVII parent. More important, none of the viruses persisted in the mouse
      CNS nor caused chronic demyelination. Thus, attenuation of GDVII neurovirulence
      alone is not sufficient to establish TMEV persistence. This result is discussed
      in the context of a genomic determinant for persistence.

PMID- 9603315
TI  - Identification of a region of the rabies virus N protein involved in direct
      binding to the viral RNA.
AB  - In rabies virus, the ribonucleoprotein complex (RNP), the RNA genome (-) and the
      antigenome (+) are specifically coated by the viral nucleoprotein (N protein),
      forming the template for transcription and replication bythe viral RNA
      polymerase. This specific encapsidation starts at the 5' ends of the RNAs. To
      investigate domains of the N protein that govern binding specificity, we tested
      in vitro the ability of both full-length and truncated forms of the N protein to
      interact with a synthetic RNA probe corresponding to the 5' end of the
      antigenome. UV-LASER cross-linking, which covalently links RNA and proteins in
      intimate contact, showed that the entire N protein (450 aa) and the NH2-terminal
      376 aa (t42) contained all of the determinants for specific interaction. It was
      demonstrated by affinity chromatography that a peptide near the COOH terminus of
      t42 (position 298352), which is located in the most conserved region of
      Rhabdoviridae N proteins, bound directly to the viral RNA. However, no
      significant sequence similarity was detected between this peptide and known RNA
      binding proteins in the databases. This suggests both that N proteins may possess
      a new type of RNA binding motif and that protein folding contributes to the
      architecture of the RNA binding site.

PMID- 9603316
TI  - Differential receptor usage by measles virus strains.
AB  - Recently, we demonstrated that infection of cells with all measles virus (MV)
      strains tested was inhibited by antibodies against CD46, although not all strains
      caused downregulation of the MV receptor CD46 from the surface of human cells. We
      now show that infection of cells with MV strain WTFb, a variant of wild-type
      isolate WTF which has been isolated and propagated on human BJAB cells, is not
      inhibited by antibodies against CD46. In contrast, infection of cells with the
      closely related strain WTFv, a Vero cell-adapted variant of WTF, is inhibited by
      antibodies against CD46. This observation led us to investigate the interaction
      of these viruses and the vaccine strain Edmonston (Edm) with CD46 and target
      cells. Cellular receptors with high affinity binding for WTFb are present on BJAB
      cells, but not on transfected CD46-expressing CHO cells. In contrast to the Edm
      strain, virus particles and solubilized envelope glycoproteins of WTFb have a
      very limited binding capacity to CD46. Furthermore, we show that recombinant
      soluble CD46 either does not bind, or binds very weakly, to WTFb glycoproteins
      expressed on the cell surface. Our findings indicate that wild-type MV strain
      WTFb and vaccine strain Edm use different binding sites on human cells. In
      addition, the results suggest that MV strains may alternatively use CD46 and an
      unknown molecule as receptors, and that the degree of usage of both receptors may
      be MV strain-specific.

PMID- 9603317
TI  - Oral or parenteral administration of replication-deficient adenoviruses
      expressing the measles virus haemagglutinin and fusion proteins: protective
      immune responses in rodents.
AB  - The genes encoding the measles virus (MV) haemagglutinin (H) and fusion (F)
      proteins were placed under the control of the human cytomegalovirus immediate
      early promoter in a replication-deficient adenovirus vector. Immunofluorescence
      and radioimmune precipitation demonstrated the synthesis of each protein and
      biological activity was confirmed by the detection of haemadsorption and fusion
      activities in infected cells. Oral as well as parenteral administration of the H
      expressing recombinant adenovirus elicited a significant protective response in
      mice challenged with MV. While the F-expressing adenovirus failed to protect
      mice, cotton rats immunized with either the H- or F-expressing recombinant showed
      reduced MV replication in the lungs. Antibodies elicited in mice following
      immunization with either recombinant had no in vitro neutralizing activity,
      suggesting a protective mechanism involving a cell-mediated immune response. This
      study demonstrates the feasibility of using oral administration of adenovirus
      recombinants to induce protective responses to heterologous proteins.

PMID- 9603318
TI  - Variation in ATP requirement during influenza virus transcription.
AB  - The ATP requirement of influenza A virus RNA-dependent RNA polymerase was studied
      during in vitro transcription reactions. In complete transcription reactions, the
      Km for ATP was 10-fold higher than the Km values for the other NTPs. However,
      during transcription elongation the Km for ATP was as low as the Km values for
      the other NTPs, suggesting a special requirement for ATP during transcription
      initiation. Gel analysis of RNA products of transcription initiation reactions
      showed that the incorporation of AMP into nascent RNA was more efficient at
      positions 4, 6 and 7 relative to the template RNA than at position 5. The
      polymerase produced short, abortive transcripts with lengths corresponding to
      positions 3 and 4 relative to the template but never to position 5 or longer.
      These results suggest that incorporation of AMP at position 5 induces the
      influenza A virus polymerase to go through a transition from a transcription
      initiation to an elongation complex. This functional change of the polymerase
      complex rather than a requirement for ATP beta-gamma bond hydrolysis is the most
      likely reason for the particularly high Km for ATP during the early phase of
      transcription. This conclusion is supported by the fact that the ATP analogue
      ATPgammaS [adenosine 5'-O-(3-thiotriphosphate)] can efficiently replace ATP in in
      vitro transcription reactions and shows a comparable drop of Km between
      transcription initiation and elongation.

PMID- 9603319
TI  - Expression of ORF A1 of infectious bursal disease virus results in the formation
      of virus-like particles.
AB  - A recombinant vaccinia virus inducibly expressing ORF A1 of infectious bursal
      disease virus (IBDV) has been constructed and characterized. Cells infected with
      this recombinant virus express the IBDV polyprotein, which is proteolytically
      processed to give mature VP2, VP3, and VP4 polypeptides. An electron microscopy
      study revealed that the cytoplasm of cells infected with the recombinant virus
      contains abundant IBDV-like particles (VLP). These VLP form close-packed
      paracrystalline arrays that are specifically recognized by anti-IBDV antibodies.
      The size and morphology of purified VLP were found to be akin to those of
      authentic IBDV particles.

PMID- 9603320
TI  - Analysis of human immunodeficiency virus type 1 env and gag sequence variants
      derived from a mother and two vertically infected children provides evidence for
      the transmission of multiple sequence variants.
AB  - In order to investigate the transmission of human immunodeficiency virus type 1
      (HIV-1) from mother-to-child we have examined serial plasma RNA samples obtained
      from a mother over an eight year period spanning four pregnancies. Child 1 and 2
      (born January 1987 and June 1990) were uninfected whilst child 3 and 4 (born July
      1992 and February 1994) were HIV positive. Genetic variation was examined within
      the viral population of the mother and her two infected children for both the V3
      loop and flanking regions of the env gene and the p17 region of the gag gene. In
      one child (child 4) a highly homogeneous virus population was observed within
      both env and gag in contrast to the more heterogeneous virus population observed
      within the mother. Viral sequences of child 4 clustered within a single branch
      within the reconstructed phylogenetic tree. This is consistent with the
      transmission of a single maternal variant to the child in this case, which may
      indicate a selective process. By contrast, child 3 showed substantial genetic
      heterogeneity even within the first samples obtained shortly after birth.
      Sequences of child 3 clustered in two distinct groups within the phylogenetic
      tree and were separated by sequences of the mother. These results are not
      consistent with the selective transmission of a single maternal variant to the
      child in this case and we therefore propose that the infection within child 3 is
      the result of the transmission of multiple sequence variants to the child. All
      transmitted sequence variants were predicted to be of the macrophage-tropic,
      nonsyncytium-inducing (NSI) phenotype.

PMID- 9603321
TI  - Interaction and co-encapsidation of human immunodeficiency virus type 1 Gag and
      Vif recombinant proteins.
AB  - Human immunodeficiency virus type 1 (HIV-1) wild-type (WT) virion infectivity
      factor (Vif) protein (Vifwt) and full-length Gag precursor (Pr55Gag) were found
      to be co-encapsidated into extracellular, membrane-enveloped virus-like particles
      released by budding from Sf9 cells co-expressing the two recombinant proteins in
      trans, with an average copy number of 3.5+/-0.6 Vifwt per 100 Pr55Gag molecules.
      No preferential localization at the plasma membrane was observed for recombinant
      Vif in the absence of Gag expression, and a significant proportion of Vif
      accumulated within the nucleus. Two conserved motifs, W89RKRRY94 and
      P156KKIKP161, seemed to act as nuclear addressing signals. The Pr55Gag and Vifwt
      interacting domains were analysed by biopanning of a phage-displayed hexapeptide
      library. The Vif-binding domain, which spanned residues H421-T470 in Pr55Gag,
      corresponded to the C-terminal region of nucleocapsid (NC), including the second
      zinc finger, the intermediate spacer peptide sp2 and the N-terminal half of the
      p6 domain. Deletions in these Gag domains significantly decreased the Vif
      encapsidation efficiency, and complete deletion of NC abolished Vif
      encapsidation. In Vif, four discrete Gag-binding sites were identified, within
      residues T68-L81 (site I) and W89-P100 (site II) in the central domain, and
      within residues P162-R173 (III) and P177-M189 (IV) at the C terminus.
      Substitutions in site I and deletion of site IV were detrimental to Vif
      encapsidation, whereas substitution of basic residues for alanine in sites III
      and IV had a positive effect. The data suggest a direct intracellular Gag-Vif
      interaction and the occurrence of a Pr55Gag-mediated membrane-targeting pathway
      for Vif in Sf9 cells.

PMID- 9603322
TI  - A role for human immunodeficiency virus type 1 Vpr during infection of peripheral
      blood mononuclear cells.
AB  - Studies analysing human immunodeficiency virus type 1 replication in primary
      cells have demonstrated that Vpr, although dispensable, plays a role along with
      the matrix (MA) protein in allowing nuclear localization of viral preintegration
      complexes in non-dividing monocyte-derived macrophages (MDMs). In the current
      study, experimental infection conditions to analyse the role of Vpr,
      independently of MA, during infection of PHA/IL-2-stimulated peripheral blood
      mononuclear cells (PBMC) were designed. It was shown that the absence of Vpr
      results in a subtle effect on virus production in long-term infection. PCR
      analysis of the steps of virus retrotranscription during a single cycle of
      replication in stimulated PBMC revealed that the absence of Vpr alone correlates
      with an impairment in the nuclear localization of viral DNA. Our data indicate
      that Vpr is involved in the virus life-cycle during infection of dividing PBMC,
      presumably as it is during infection of MDMs.

PMID- 9603323
TI  - Nucleotide substitutions in the long terminal repeat are not required for
      development of neurovirulence by simian immunodeficiency virus strain mac.
AB  - The question of whether consensus nucleotide substitutions in the long terminal
      repeat (LTR) region of simian immunodeficiency virus strain mac (SIVmac) are
      important for neurovirulence was investigated in this report. Brains and lymph
      nodes from two macaques that developed AIDS and encephalitis following
      inoculation with two strains of neurovirulent SIVmac, and from one animal with
      AIDS but no neurological disease after inoculation with non-neurovirulent
      SIVmac239 were used. The 5' LTR regions from neurovirulent SIVmacR71/17E and
      SIVmac7F-Lu were amplified, cloned and sequenced and these sequences were
      compared to the LTRs amplified from three regions of the respective encephalitic
      brains and lymph nodes from macaques inoculated with each virus. The SIVmac7F-Lu
      and SIVmacR71/17E viruses had zero and three consensus substitutions,
      respectively, in the U3, R and U5 regions of the LTR compared to that of
      SIVmac239. The only consensus substitution in the LTR-gag region of the genome
      was a T to C change at position 829 within the tRNA binding site. The sequences
      amplified from the brain and lymph nodes of the two animals with AIDS and
      encephalitis were identical. This single common substitution in this region of
      the virus genome, the T to C substitution at position 829, was also found in the
      LTRs isolated from the brain and lymphoid organs from the macaque inoculated with
      SIVmac239. The virtual identity in nucleotide sequences in the LTR of the
      neurovirulent and non-neurovirulent viruses and in CNS and lymph tissues of
      animals inoculated with the viruses suggests that the LTR has no effect on the
      tissue tropisms of the viruses.

PMID- 9603324
TI  - Spacing between the enhancer and promoter of the long terminal repeat of a murine
      leukaemia retrovirus is required for transcriptional activation in T cells.
AB  - In T cells, transcriptional activation by the long terminal repeat (LTR) of the
      mink cell focus-forming murine leukaemia virus requires some spacing between the
      enhancer and promoter. A large size-range of intervening sequences (11-93 bp) is
      able to activate transcription efficiently. Neither a specific nucleotide
      sequence nor stereospecific alignment of the spacer is important.

PMID- 9603325
TI  - Characterization and phylogenetic analysis of a novel hepatitis D virus strain
      discovered by restriction fragment length polymorphism analysis.
AB  - The hepatitis D virus (HDV) genotypes in 46 HDV-infected patients and 12
      prostitutes were screened with Xhol restriction fragment length polymorphism
      (RFLP) analysis of reverse transcription PCR products of viral genomes and
      verified by phylogenetic analysis. The amplificates of three (6.5%) patients and
      two (17%) prostitutes showed a novel RFLP pattern different from those of the
      three known genotypes. Complete HDV genomic sequence identities between isolates
      with a novel RFLP and the HDV genotypes I, II and III were 72.3, 77.2 and 63.0%,
      respectively. Importantly, divergence was mostly seen in various regions related
      to replication or packaging. The novel isolates formed a monophyletic group (P <
      0.05) and were most closely related to genotype II.

PMID- 9603326
TI  - Interaction between hepatitis delta virus-encoded proteins and hepatitis B virus
      envelope protein domains.
AB  - Hepatitis delta virus (HDV) packaging requires prenylation of the HDV large
      protein (p27), as well as a direct protein-protein interaction between HDV
      proteins and hepatitis B virus (HBV) envelope protein domains. To investigate
      this interaction, we have analysed the binding capacity of baculovirus-expressed
      delta p24 and p27 proteins to synthetic peptides specific for the HBV envelope.
      Although a higher degree of binding was observed with p27, both p24 and p27 could
      bind HBV envelope peptides. One such peptide corresponded to residues 56-80
      located in the cytosolic loop of the small HBV envelope protein, and another
      corresponded to 23 carboxy-terminal residues of the pre-S1 specific to the large
      HBV envelope protein. This indicates that in addition to p27, p24 may contribute
      to packaging of HDV through a protein-protein interaction with HBV envelope
      domains, and that an interaction between the pre-S1 polypeptide and delta
      proteins may play a role in infectivity.

PMID- 9603327
TI  - In vitro activity of hepatitis B virus polymerase: requirement for distinct metal
      ions and the viral epsilon stem-loop.
AB  - Hepadnaviruses have a complex replication cycle which includes reverse
      transcription of the pregenomic RNA. The initial step in this process in
      hepatitis B virus (HBV) requires the viral polymerase to engage a highly stable
      region of secondary structure within the pregenomic RNA termed the epsilon stem
      loop. While reverse transcriptases belonging to the retrovirus family use a
      specific cellular tRNA as primer, HBV polymerase utilizes a tyrosine residue
      located within its own N terminus. Therefore, the first deoxyribonucleotide is
      covalently coupled to HBV polymerase prior to extension of the DNA strand by
      conventional reverse transcription. We have expressed HBV polymerase in a
      baculovirus and following purification have found it to be active with respect to
      protein-priming and reverse transcription of copurified RNA. Importantly, we
      found both of these processes to be critically dependent on the presence of the
      epsilon stem-loop. The metal ion preferences of HBV polymerase were also
      investigated for both the protein-priming and reverse transcription activities of
      this enzyme. Reverse transcription was dependent on magnesium, with an optimal
      concentration of 5 mM. However, protein-priming was strongly favoured by
      manganese ions and was optimal at a concentration of 1 mM. Thus, using manganese
      as sole source of metal ions our activity assay is restricted to the protein
      priming event and will allow the search for novel antivirals specifically
      blocking this unique mechanism.

PMID- 9603328
TI  - Calcium is required in reassembly of bovine papillomavirus in vitro.
AB  - Papillomaviruses are small DNA viruses which infect and induce benign warts and
      sometimes malignant tumours in the epithelium of the skin or mucosa. The viruses
      do not replicate in conventional tissue culture systems and little is known about
      the requirements for virus assembly. We investigated the effect of ethylene
      glycol-bis(aminoethyl ether)-tetraacetic acid (EGTA) and dithiothreitol (DTT)
      treatment on the stability of bovine papillomavirus type 1 (BPV-1) particles in
      vitro. Removal of calcium ions by 11 mM EGTA at pH 8.0 together with reduction of
      disulfide bonds by 15 mM DTT destabilized BPV particles. Electron microscopy
      examination of treated particles showed that the BPV particles had been disrupted
      to capsomeres. Addition of exogenous calcium ions to the disruption buffer
      prevented virus destabilization. Adding calcium to the disrupted BPV particles
      resulted in the reassembly of disrupted particles. The reassembled particles were
      morphologically similar to intact BPV virions. We further quantified the
      efficiency of reassembly by focus formation assay. We recorded 500-fold less
      infectivity for reassembled BPV and 4-fold less haemagglutination activity
      compared to untreated BPV, pointing towards a decrease in the amount of
      reassembled particles recovered.

PMID- 9603329
TI  - JC virusType 2: definition of subtypes based on DNA sequence analysis of ten
      complete genomes.
AB  - Five major genotypes of JC virus (JCV) have been defined based on nucleotide
      differences in the VP1 gene of the DNA sequence. These types are probably a
      result of virus evolution in geographically isolated population groups. One of
      the first genotypes identified, Type 2, was found to represent strains of Asian
      origin. In order to further define the spectrum within Type 2 strains, the entire
      5.1 kb genome of nine urinary strains of JCV was amplified by PCR with one pair
      of primers. These urine samples were obtained in the USA (California and New
      Mexico) from three European Americans, three Native Americans, two African
      Americans and one Hispanic American. The complete genome of an Asian JCV strain
      (Tokyo-1) isolated from progressive multifocal leukoencephalopathy (PML) brain in
      Japan was also sequenced. Here, we report the analysis of these ten DNA sequences
      and their deduced protein translations. Two phylogenetically distinct subtypes of
      Type 2 were found, 2A and 2B, which differ from each other by 0.8-1.1% of the
      coding region sequence. A 215 bp product amplified with primers in the VP1 gene
      contains enough sequence information to distinguish the major types and subtypes
      of JCV and is suitable for application in viral epidemiological studies. The
      investigation of these genomic variations is of special interest because JCV Type
      2 strains are found at a significantly higher frequency in brain tissue of
      patients with PML than would be predicted from their excretion in a control
      population.

PMID- 9603330
TI  - No evidence for a role of modified live virus vaccines in the emergence of canine
      parvovirus.
AB  - In this study the early evolution and potential origins of canine parvovirus
      (CPV) were examined. We cloned and sequenced the VP2 capsid protein genes of
      three German CPV strains isolated in 1979-1980, as well as two feline
      panleukopenia virus (FPV) vaccine viruses that were previously shown to have some
      restriction enzyme cleavage sites in common with CPV. Other partial VP2 gene
      sequences were obtained by amplifying CPV DNA from paraffin-embedded tissues of
      dogs which were early parvovirus disease cases in Germany in 1978-1979. Sequences
      were analysed with respect to their evolutionary relationships to other CPV and
      FPV isolates. Those analyses did not support the hypothesis that CPV emerged as a
      variant of an FPV vaccine virus. Neither did they reveal ancestral sequences
      among the very early CPV isolates examined. Other possible sources for the origin
      of CPV are examined, including the involvement of viruses from wild carnivores.

PMID- 9603331
TI  - Modified vaccinia virus Ankara undergoes limited replication in human cells and
      lacks several immunomodulatory proteins: implications for use as a human vaccine.
AB  - Modified virus Ankara (MVA) is a vaccinia virus (VV) strain that was attenuated
      by serial passage through chick embryo fibroblasts (CEFs) and contains six large
      genomic deletions compared with parental virus. MVA replicates well in CEFs, but
      poorly in most mammalian cells. Recombinant MVA is a promising human vaccine
      candidate due to its restricted host range, immunogenicity and avirulence in
      animal models, and excellent safety record as a smallpox vaccine. Here we present
      a further characterization of MVA and demonstrate that: (i) MVA can replicate,
      albeit poorly, in transformed human cell lines, but not in primary human
      fibroblasts although there is limited cell-to-cell spread; (ii) MVA is a potent
      inducer of type I interferon (IFN) from primary human cells, which may restrict
      virus spread in vivo; and (iii) unlike other VV strains, MVA does not express
      soluble receptors for IFN-gamma, IFN-alpha/beta, tumour necrosis factor and CC
      chemokines, but does express a soluble interleukin-1beta receptor. This provides
      a plausible and testable explanation for the good immunogenicity of MVA despite
      its poor replication in mammals. The implications of these findings for the use
      of MVA as a safe and immunogenic human vaccine candidate are discussed.

PMID- 9603332
TI  - Expression of African swine fever virus envelope protein j13L inhibits vaccinia
      virus morphogenesis.
AB  - The African swine fever virus (ASFV) strain Malawi LIL20/1 open reading frame
      (ORF) j13L was expressed in vaccinia virus (VV) from a strong synthetic late
      promoter as either a complete ORF (vSJ1) or lacking codons 1-31 (vSJ2). Each
      recombinant VV produced a small plaque which rapidly reverted to a normal size
      upon passage. The yield of infectious virus from a single cycle infection with
      vSJ1 or vSJ2 was reduced 50- to 100-fold compared to wild-type (wt) and a
      revertant virus (vSJ5) in which the j13L ORF was removed and the VV thymidine
      kinase gene restored. PCR analysis of nine spontaneous large plaque revertant
      viruses, recovered after passage of vSJ1 in BSC-40 cells, showed that six had
      lost the j13L ORF and the co-inserted beta-galactosidase gene. Three viruses
      retained the j13L and beta-galactosidase genes, but in each case the j13L protein
      was not expressed due to a different single base deletion near the 5' end of the
      j13L coding region which introduced a stop codon a short distance downstream. The
      formation of intracellular mature virus (IMV) and extracellular enveloped virus
      was reduced 50- to 75-fold in cells infected with vSJ1 compared to wt VV and
      revertant vSJ5. Electron microscopy showed aberrant IMV precursor structures in
      vSJ1-infected cells, and immunoelectron microscopy demonstrated that these
      structures contained j13L protein. These results indicate that expression of the
      j13L protein is toxic for VV replication due to interference with VV
      morphogenesis prior to IMV formation.

PMID- 9603333
TI  - Characterization of African swine fever virion proteins j5R and j13L: immuno
      localization in virus particles and assembly sites.
AB  - The j5R open reading frame (ORF) of the Malawi LIL 20/1 African swine fever virus
      (ASFV) isolate encodes a 111 amino acid protein with a putative transmembrane
      domain at the N terminus. Antisera raised against the predicted C-terminal
      peptide were used to identify the j5R protein by Western blotting in cells
      infected with ASFV or with recombinant vaccinia virus expressing the j5R ORF.
      This showed that the j5R protein migrates with an apparent molecular mass of 23
      25 kDa, depending on the virus isolate, on SDS-PAGE and is expressed late during
      ASFV infection. The localization in infected cells and in virions of the j5R
      protein, and that of a previously characterized virion protein, j13L, which also
      contains a putative transmembrane domain, were studied by immunofluorescence and
      immuno-electron microscopy. Both proteins were expressed at 8-10 h post-infection
      (p.i.) as small multiple perinuclear foci which coalesced to a single area
      indicative of the virus factory at 18 h p.i. At the ultrastructural level j5R and
      j13L were detected mainly on membrane-like structures within the virus factory
      and on virus particles, suggesting that they may be involved in particle
      assembly. Negative contrast immuno-electron microscopy of mature extracellular
      virions confirmed that they are also integral structural proteins.

PMID- 9603334
TI  - A conserved African swine fever virus right variable region gene, l11L, is non
      essential for growth in vitro and virulence in domestic swine.
AB  - The right variable region of the African swine fever virus (ASFV) genome is known
      to contain genes with functions involving virus virulence and host range in
      swine. A novel open reading frame, ORF l11L, which was absent in the non
      pathogenic, cell culture-adapted European isolate BA71V, was identified in the
      pathogenic African isolate Malawi Lil-20/1. The location of l11L in the right
      variable region, together with its absence in BA71V, suggested that l11L may have
      a function in virus virulence and/or host range. Here, we show that the l11L gene
      is highly conserved among pathogenic African, European and Caribbean ASFV field
      isolates and that it exists either in a short form, encoding a protein of 77-78
      amino acids (9.1 kDa) or in a longer form of 93-94 amino acids (11.1 kDa). The
      presence of two predicted membrane-spanning segments suggests that l11L is an
      integral membrane protein. RT-PCR analysis demonstrated that l11L mRNA is
      expressed late in the virus replication cycle. A recombinant l11L gene deletion
      mutant, deltal11L, was constructed from the ASFV isolate Malawi Lil-20/1 to
      examine gene function. Deletion of l11L did not affect virus replication in swine
      macrophage cell cultures nor virulence in domestic pigs, indicating that l11L is
      non-essential for growth in vitro and for virus virulence in domestic swine.

PMID- 9603335
TI  - The DNA sequence of equine herpesvirus-4.
AB  - The complete DNA sequence of equine herpesvirus-4 (EHV-4) strain NS80567 was
      determined. The genome is 145597 bp in size and consists of a long unique region
      (UL, 112398 bp) flanked by a short inverted repeat (TRL/IRL, 27 bp) linked to a
      short unique region (Us, 12789 bp) flanked by a substantial inverted repeat
      (TRs/IRs, 10178 bp). EHV-4 is predicted to contain 76 different genes; three of
      these are present twice in TRs/IRs, giving a total of 79 genes. The closely
      related virus equine herpesvirus-1 (EHV-1) also possesses 76 different genes
      corresponding to those of EHV-4, but has a total of 80 genes because four are
      present twice in TRs/IRs. Interpretations of the coding capacity of the EHV-4 and
      EHV-1 genomes were refined by comparing the complete DNA sequences.

PMID- 9603336
TI  - Equine herpesvirus-4 glycoprotein G is secreted as a disulphide-linked homodimer
      and is present as two homodimeric species in the virion.
AB  - Glycoprotein G (gG) homologues have been found in most alphaherpesviruses
      although little is known about their structure or function. In this study, three
      species of equine herpesvirus-4 (EHV-4) gG were identified: a full-length 68 kDa
      virion-associated species (gGVL), a 12 kDa virion-associated species (gGVS) and a
      60 kDa secreted species (gGS), detected in the medium of infected cells. gGS and
      gGVS appear to be proteolytic cleavage products of gGVL and correspond to the N-
      and C-terminal regions, respectively. It was shown that gGS and gGVL are
      similarly glycosylated possessing mostly N-linked complex-type carbohydrate side
      chains. Western blots of proteins separated under nonreducing conditions
      established that gGS is secreted as a 120 kDa glycoprotein while the virion
      associated species, gGVL and gGVS, are present in the virion as 140 and 20 kDa
      proteins, respectively. As gGS and gGVL do not appear to associate stably with
      other viral proteins, it is most likely that each species exists as a disulphide
      linked homodimer. Pulse-chase experiments indicated that gGVL is rapidly
      assembled as a homodimer prior to both carbohydrate side-chain maturation in the
      Golgi and proteolytic cleavage. Proteolytic cleavage of full-length gG occurs
      during or immediately after passage through the Golgi. Secreted and virion
      associated species of gG were identified in the closely related virus EHV-1 and
      were of similar molecular masses to the corresponding EHV-4 gG species.

PMID- 9603337
TI  - Localization of type-specific epitopes of herpes simplex virus type 2
      glycoprotein G recognized by human and mouse antibodies.
AB  - Glycoprotein G is a major target for the humoral immune response against herpes
      simplex virus (HSV) and a prototype antigen for type-specific serodiagnosis
      discriminating HSV-1 and HSV-2 infections. The mature part of HSV-2 glycoprotein
      G-2 (gG-2) contains a unique stretch suspected to mediate type specificity, and
      in addition a region homologous to HSV-1 glycoprotein G-1 (gG-1). Antigenic
      determinants of the mature gG-2 were mapped by testing the reactivity of mouse
      anti-gG-2 monoclonal antibodies (MAbs) and purified human anti-gG-2 antibodies
      with synthetic peptides coupled to cellulose membranes. The anti-gG-2 MAbs bound
      to four epitopes localized in a narrow cluster within a gG-2 segment delimited by
      amino acids (aa) 552 and 611. This cluster was located between the predicted O
      glycan-rich region and the transmembrane anchor sequence. The epitopes of the
      human anti-gG-2 antibodies were localized within three stretches of amino acids,
      two of which were overlapping with those recognized by anti-gG-2 MAbs. One of
      these stretches, delimited by aa 552 and 574, showed reactivity to all human HSV
      2 sera tested, but not to HSV-1 sera or to purified anti-gG-1 antibodies. Neither
      the anti-gG-2 MAbs nor the purified human anti-gG-2 antibodies were cross
      reactive to gG-1 peptides or HSV-1 antigen, although most of the epitopes were
      localized within the part of gG-2 which was homologous to gG-1. The findings
      concerning HSV-2 type-specific human antibody response to a defined stretch
      within gG-2 may be of importance for the further development of type
      discriminating serodiagnosis.

PMID- 9603338
TI  - Herpes simplex virus hepatitis in macrophage-depleted mice: the role of massive,
      apoptotic cell death in pathogenesis.
AB  - Infection with herpes simplex virus or hepatitis viruses can lead to fulminant
      hepatitis, but there is controversy about the underlying conditions needed for
      such disease. To investigate how the impairment of host defences might be
      involved, macrophages were depleted by administration of silica to mice before
      intravenous injection with herpes simplex virus type 1 (HSV-1). Such mice died
      rapidly and their livers were yellowish and shrunken (acute yellow atrophy), and
      occasionally grossly haemorrhagic. Small foci of apoptotic cells developed in the
      liver lobules; these rapidly became confluent and zonal over time. The overall
      lesion pattern was similar to massive hepatic necrosis, and there was extensive
      HSV replication in the liver lesions. In the liver, DNA fragmentation
      characteristic of apoptosis followed the time course of HSV-1 propagation. These
      findings suggest that one of the underlying conditions for fulminant viral
      hepatitis may be inadequate macrophage response, and that the massive hepatic
      damage, often defined as cell necrosis, may actually be apoptosis of liver cells
      subsequent to virus infection.

PMID- 9603339
TI  - Disruption of PML-associated nuclear bodies mediated by the human cytomegalovirus
      major immediate early gene product.
AB  - The PML gene product is associated with a defined nuclear structure (10-20 per
      cell) known variously as PML-bodies, ND10, PODs or Kr bodies. Certain conditions
      are known to compromise the integrity of PML-bodies; these include environmental
      stress (e.g. heat shock), a chromosomal translocation-associated acute
      promyelocytic leukaemia, and infection with certain viruses [including human
      cytomegalovirus (HCMV), herpes simplex virus type 1 and adenovirus]. Expression
      of the HCMV major immediate early (IE) protein (IE1(491aa)) is by itself
      sufficient to cause disruption of PML-bodies, resulting in the dispersal of the
      PML antigen uniformly throughout the nucleus. In uninfected cells undergoing
      mitosis PML is excluded from chromatin. However, both IE1(491aa) and PML were
      observed to associate with mitotic chromosomes in cells infected with HCMV or
      transfected with the IE1 gene. A series of in-frame IE1 deletion mutants was used
      in DNA transfection experiments to identify two large sequence elements (aa 132
      274 and the C-terminal aa 347-491) not required for dispersal of the PML antigen.
      However, a putative leucine-zipper domain (aa 105-139), a putative zinc-finger
      domain (aa 267-286) and exon 2 and 3 coding sequences (aa 6-85) were required.
      The association of the IE1 gene product with chromatin required an acidic domain
      near the C terminus (aa 421-486). The interaction of IE1(491aa) with chromatin
      was therefore not required for the disruption of PML-bodies. Exon 2 (aa 1-24) was
      shown to encode a nuclear localization signal.

PMID- 9603340
TI  - Chronic infection of human umbilical vein endothelial cells by human herpesvirus
      6.
AB  - Human herpesvirus-6 (HHV-6) exhibits a predominant tropism for CD4+ T
      lymphocytes, but can infect other components of the blood as well as surrounding
      tissue and organs. To understand the role of the endothelium in the transmission
      and haematogenous spread of this virus, human umbilical vein endothelial cells
      (HUVEC) were infected with HHV-6 and monitored for viral gene expression. The
      presence of both early and late viral antigens was demonstrated by indirect
      immunofluorescence in 37.6 and 6.5%, respectively, of HUVEC. However, attempts to
      detect the release of infectious virus were not successful, indicating infection
      is semipermissive in nature. Upon continued passage of infected HUVEC monolayers,
      HHV-6 antigen-positive cells persisted up to 27 days post-infection. Furthermore,
      the virus could be recovered from HUVEC monolayers that contained fewer than 1%
      antigen-positive cells by co-cultivation with peripheral blood mononuclear cells.
      Together, these findings suggest that endothelial cells may serve as a reservoir
      for harbouring HHV-6.

PMID- 9603342
TI  - Recombination between viral DNA and the transgenic coat protein gene of African
      cassava mosaic geminivirus.
AB  - Nicotiana benthamiana was transformed with three different constructs (pCRA1,
      pCRA2 and pJC1) containing the coat protein coding sequence of African cassava
      mosaic virus (ACMV). Transformed plants were inoculated with a coat protein
      deletion mutant of ACMV that induces mild systemic symptoms in control plants.
      Several inoculated plants of transgenic lines CRA1/3, CRA1/4, CRA2/1 and CRA2/2
      developed severe systemic symptoms typical of ACMV. DNA analysis revealed that,
      in these plants, recombination had occurred between the mutant viral DNA and the
      integrated construct DNA, resulting in the production of recombinant virus
      progeny with 'wild-type' characteristics. No reversion of mutant to 'wild-type'
      virus was observed in pJC1-transformed plants. Recombinant virus from several
      transgenic plants was analysed by PCR and parts of DNA A of virus progeny were
      cloned. Sequence analysis revealed that only a few nucleotides were changed from
      the published sequence.

PMID- 9603341
TI  - Overexpression, purification and helix-destabilizing properties of Epstein-Barr
      virus ssDNA-binding protein.
AB  - The Epstein-Barr virus (EBV) ssDNA-binding protein (SSB) encoded by the BALF2
      gene is one of the essential replication proteins in the lytic phase of EBV DNA
      replication. In order to obtain the amount of EBV SSB required for
      characterization, a recombinant baculovirus containing the complete sequence of
      the BALF2 open reading frame under the control of the baculovirus polyhedrin
      promoter was constructed. Insect cells infected with the recombinant virus
      produced a protein of 130 kDa, recognized by anti-BALF2 protein-specific
      polyclonal antibody. The overexpressed EBV SSB was purified homogeneously from
      the cytosolic fraction of the recombinant virus-infected cells. The purified
      protein displaced short DNA strands from their complementary sequences in the
      single-stranded form of M13. The helix-destabilizing activity was neutralized by
      the anti-BALF2 protein-specific antibody. Maximum unwinding occurred at EBV SSB
      concentrations exceeding saturation level of the DNA substrate. The DNA unwinding
      reaction mediated by the EBV SSB was highly cooperative and extremely rapid. The
      reaction displayed no directionality and required neither ATP nor MgCl2, two
      essential cofactors for DNA helicase activity. The helix-destabilizing property
      of the EBV SSB may function to melt out secondary structures on the ssDNA
      template, thereby facilitating the movement of the EBV DNA polymerase.

PMID- 9603343
TI  - Nucleic acid-binding properties and subcellular localization of the 3a protein of
      brome mosaic bromovirus.
AB  - Brome mosaic bromovirus (BMV) 3a protein is required for cell-to-cell movement of
      the virus in host plants. The BMV 3a protein (B3a) was produced in Escherichia
      coli using an expression vector. Gel retardation analysis and UV cross-linking
      experiments demonstrated that B3a bound single-stranded RNA cooperatively without
      sequence specificity. Binding competition analysis showed that B3a bound to
      single-stranded nucleic acids more strongly than to double-stranded nucleic
      acids. Deletion mutagenesis located a nucleic acid-binding domain to amino acids
      189-242. Western blot analysis of fractionated proteins of BMV-infected barley
      using monoclonal antibodies against B3a indicated that B3a may interact with
      membrane materials and form complexes in the cytoplasm. Immunogold labelling of
      thin sections of infected barley tissues revealed that B3a was associated with
      plasmodesmata and cytoplasmic inclusions.

PMID- 9603344
TI  - Immunological detection and mutational analysis of the RNA2-encoded nematode
      transmission proteins of pea early browning virus.
AB  - Pea early browning virus (PEBV) is transmitted between plants by root-feeding
      trichodorid nematodes. Mutagenesis studies have implicated two non-structural
      viral proteins in the transmission process. These two proteins [the 29 kDa
      ('29K') protein and the 23K protein] were expressed in bacteria and used to raise
      antibodies. In Western blotting experiments, the antibodies detected both of
      these virus proteins in leaves and roots of infected Nicotiana bethamiana and N.
      clevelandii plants. Periodate treatment of proteins transferred to nitrocellulose
      membranes suggested that the PEBV 23K protein may be glycosylated. A PEBV mutant
      was constructed lacking the complete 23K coding sequence. The mutant was able
      systemically to infect Nicotiana spp. but caused striking chlorotic ringspot leaf
      symptoms and stunting of both leaves and roots. These symptoms were absent in
      plants doubly-infected with the mutant and wild-type PEBV. The 23K gene deletion
      mutant was transmitted by nematodes at a much reduced frequency compared to wild
      type virus, indicating that the 23K protein is involved in but not essential for
      vector transmission. Western immuno-blot and ELISA experiments revealed that the
      reduction in the nematode-transmissibility of PEBV carrying mutations in the 23K
      gene did not result from interference in the expression of the 29K transmission
      protein or from gross changes in the titre of virus in the roots of infected
      plants.

PMID- 9603345
TI  - Nucleotide sequence and genome organization of grapevine leafroll-associated
      virus-2 are similar to beet yellows virus, the closterovirus type member.
AB  - The entire genome of grapevine leafroll-associated closterovirus-2 (GLRaV-2),
      except the exact 5' terminus, was cloned and sequenced. The sequence encompasses
      nine open reading frames (ORFs) which include, in the 5' to 3' direction, an
      incomplete ORF1a encoding a putative viral polyprotein and eight ORFs that encode
      proteins of 52 kDa (ORF1b), 6 kDa (ORF2), 65 kDa (ORF3), 63 kDa (ORF4), 25 kDa
      (ORF5), 22 kDa (ORF6), 19 kDa (ORF7) and 24 kDa (ORF8) respectively, and 216
      nucleotides of the 3' untranslated region. An incomplete ORF1a potentially
      encoded a large polyprotein containing the conserved domains characteristic of a
      papain-like protease, methyltransferase and helicase. ORF1b potentially encoded a
      putative RNA-dependent RNA polymerase. The expression of ORF1b may be via a +1
      ribosomal frameshift mechanism, similar to other closteroviruses. A unique gene
      array, which is conserved in other closteroviruses, was also identified in GLRaV
      2; it includes genes encoding a 6 kDa small hydrophobic protein, 65 kDa heat
      shock protein 70, 63 kDa protein of function unknown, 25 kDa coat protein
      duplicate and 22 kDa coat protein. Identification of ORF6 (22 kDa) as the coat
      protein gene was further confirmed by in vivo expression in E. coli and
      immunoblotting. Phylogenetic analysis comparing different genes of GLRaV-2 with
      those of other closteroviruses demonstrated a close relationship with beet
      yellows virus (BYV), beet yellow stunt virus and citrus tristeza virus. GLRaV-2
      is the only closterovirus, so far, that matches the genome organization of the
      type member of the group, BYV, and thus can be unambiguously classified as a
      definitive member of the genus Closterovirus.

PMID- 9603346
TI  - Nucleotide sequence of the 3'-terminal two-thirds of the grapevine leafroll
      associated virus-3 genome reveals a typical monopartite closterovirus.
AB  - The RNA genome of grapevine leafroll-associated closterovirus-3 (GLRaV-3) was
      cloned as a cDNA generated from GLRaV-3-specific dsRNA, and a partial genome
      sequence of 13154 nucleotides (nt) including the 3' terminus was determined. The
      sequenced portion contained 13 open reading frames (ORFs) potentially encoding,
      in the 5'-3' direction, proteins of > 77 kDa (ORF1a; helicase, HEL), 61 kDa
      (ORF1b; RNA-dependent RNA polymerase, RdRp), 6 kDa (ORF2), 5 kDa (ORF3, small
      transmembrane protein), 59 kDa (ORF4; heat shock protein 70, HSP70), 55 kDa
      (ORF5), 35 kDa (ORF6; coat protein, CP), 53 kDa (ORF7; diverged coat protein,
      CPd), 21 kDa (ORF8), 20 kDa (ORF9), 20 kDa (ORF10), 4 kDa (ORF11), 7 kDa (ORF12),
      and an untranslated region of 277 nt. ORF1b is probably expressed via a +1
      ribosomal frameshift mechanism, most similar to that of lettuce infectious
      yellows virus (LIYV). Phylogenetic analysis using various gene sequences (HEL,
      RdRp, HSP70 and CP) clearly demonstrated that GLRaV-3, a mealybug-transmissible
      closterovirus, is positioned independently from aphid-transmissible monopartite
      closteroviruses (beet yellows, citrus tristeza and beet yellows stunt) and
      whitefly-transmissible bipartite closterovirus (lettuce infectious yellows,
      LIYV). However, another alleged mealybug-transmissible closterovirus, little
      cherry virus, was shown to be more closely related to the whitefly-transmissible
      LIYV than to GLRaV-3.

PMID- 9603347
TI  - Molecular characterization and expression of the Trichoplusia ni granulovirus
      helicase gene.
AB  - A putative DNA helicase gene from the granulovirus of Trichoplusia ni (TnGV) was
      cloned, sequenced, and compared with the corresponding gene of several
      multinucleocapsid nucleopolyhedroviruses (MNPVs) including those from Autographa
      californica (AcMNPV), Orgyia pseudotsugata (OpMNPV), Bombyx mori (BmNPV), and
      Spodoptera exigua (SeMNPV). The TnGV helicase gene (p137) encoded a helicase of
      1158 amino acids with a predicted mass of 137 kDa. Comparison of p137 with AcMNPV
      p143 revealed 44.5% identity at the nucleotide level, and, respectively, 28.6%
      identity and 53.0% similarity at the amino acid level. Similar levels of identity
      and similarity were obtained when TnGV p137 was compared with the corresponding
      helicase genes of BmNPV, OpMNPV and SeMNPV. Using an antisense probe made from an
      internal 1.6 kb region of p137, a major transcript of approximately 3600 nt was
      detected by Northern blot analysis in fat body tissue from TnGV-infected larvae
      of T. ni. As both TnGV and AcMNPV replicate efficiently in larvae of T. ni, these
      results demonstrate that baculovirus putative DNA helicases which have diverged
      markedly can function efficiently in the same host. Three genes flanking TnGV
      p137, designated ORF68, ORF219 and ORF157, corresponded in order and orientation
      with AcMNPV ORFs 93, 94 and 96. However, the amino acid similarity between
      corresponding genes ranged from only 50.4 to 62.5%, providing further evidence
      that related baculovirus proteins which have diverged markedly can function
      efficiently in the same host.

PMID- 9603348
TI  - Size and components of poult yolk sacs.
AB  - An experiment was designed to examine the effects of strain of turkey, size of
      egg, and stage of embryonic development on yolk and yolk sac utilization. Sixty
      eggs from Nicholas and British United Turkeys of America (BUTA) breeders were
      selected within each of the weight categories 70 to 76, 80 to 86, and 90 to 96 g.
      These eggs were incubated under commercial conditions, and eggs selected at 0 or
      25 d incubation, at hatch, and 24 h posthatch and yolk and embryos were weighed
      and assayed for fat, protein, or fatty acids. Yolk weight declined from 23.7 g at
      setting to 4.66 g at hatch and subsequently to 2.87 g, 24 h posthatch. Yolk
      weight was affected by strain and egg weight and a number of significant (P <
      0.05) interactions were observed. Nicholas strain birds yielded the largest
      yolks, with the strain difference being most pronounced for the largest egg
      weight category. Larger turkey eggs contained more water, such that at 24 h
      posthatch there was double the amount of residual water in the yolk sac. At 24 h
      posthatch, the Nicholas poults had more water available in the residual yolk. Egg
      weight had little effect on lipid reserve in the yolk or yolk sac after 25 d
      incubation. Fatty acid profile of yolk lipids changed little throughout
      incubation. A number of strain differences are seen in fatty acid profile in the
      yolk during utilization, although these are quite small and may not be of
      sufficient magnitude to account for any strain differences seen in early poult
      viability or growth. Data suggests that the poult and chick may be different in
      metabolism of various lipid fractions, although in general nutrient utilization
      by the poult follows a fairly well established sequence of events.

PMID- 9603349
TI  - Effects of glucose in drinking water on the changes in whole blood viscosity and
      plasma osmolality of broiler chickens during high temperature exposure.
AB  - This study was conducted to elucidate the influence of glucose in drinking water
      on whole blood viscosity and plasma osmolality of broilers during high
      temperature exposure. Two groups of birds, which had ad libitum access to either
      a 4% glucose-water solution (Group G) or tap water (Group W), were exposed
      simultaneously to 30 C from 0300 h for 12 h each day for 3 d. During the
      experimental period, Group G birds had greater metabolic energy intake and body
      weight gain than Group W. Hematocrit and whole blood viscosity decreased
      significantly at 30 C compared to controls at 20 C in Group W, whereas, in Group
      G, no changes were found for these two variables. Plasma osmolality also
      decreased at 30 C compared to 20 C in Group W, whereas no change was noted in
      this variable in Group G. However, at 20 C, plasma osmolality was significantly
      higher in Group W than in Group G, but no difference was observed between the two
      groups at 30 C. Plasma protein concentration decreased during exposure to 30 C in
      both groups, but the decrease tended to be greater in Group W than in Group G.
      These results suggest that glucose intake may alleviate the influence of heat
      stress on whole blood viscosity and plasma osmolality.

PMID- 9603350
TI  - Evaluation of transgenic event 176 "Bt" corn in broiler chickens.
AB  - A 38-d feeding study evaluated whether standard broiler diets prepared with
      transgenic Event 176-derived "Bt" corn (maize) grain had any adverse effects on
      male or female broiler chickens as compared to diets prepared with nontransgenic
      (isogenic) control corn grain. No statistically significant differences in
      survival or BW were observed between birds reared on mash or pelleted diets
      prepared with transgenic corn and similar diets prepared using control corn.
      Broilers raised on diets prepared from the transgenic corn exhibited
      significantly better feed conversion ratios and improved yield of the Pectoralis
      minor breast muscle. Although it is not clear whether this enhanced performance
      was attributable to the transgenic corn per se, or due to possible slight
      differences in overall composition of the formulated diets, it was clear that the
      transgenic corn had no deleterious effects in this study.

PMID- 9603351
TI  - The effects of dexamethasone immunosuppression on turkey osteomyelitis complex in
      an experimental Escherichia coli respiratory infection.
AB  - Six hundred male turkeys were maintained in floor pens for 5 wk at which time
      half of the birds were given three intramuscular injections of 2 mg/kg BW of
      dexamethasone (DEX) on alternating days. On the day of the third DEX injection,
      the left thoracic air sac of each bird was injected with sterile tryptose
      phosphate broth (TPB) or with TPB containing approximately 1 x 10(2), 1 x 10(3),
      1 x 10(4), or 1 x 10(5) cfu of Escherichia coli. All mortalities and birds
      necropsied at 14 and 15 d postchallenge were scored for air
      sacculitis/pericarditis (AS) and turkey osteomyelitis complex (TOC). Cumulative
      mortality and AS score were both increased by either DEX treatment or E. coli.
      Although TOC incidence was significantly increased by the lowest titer of E. coli
      inoculation, increasing the number of bacteria inoculated did not increase TOC
      incidence due to increased mortality before TOC lesions developed. The DEX
      treatment by itself increased TOC incidence and there was a synergistic
      interaction between DEX treatment and E. coli on TOC incidence. Both DEX
      treatment and E. coli significantly decreased BW. Relative weights of liver,
      heart, and spleen were significantly increased by both E. coli and DEX, whereas
      both treatments significantly decreased relative weight of the bursa of
      Fabricius. The number of positive bacterial isolations from tissue and the
      heterophil to lymphocyte ratio were increased by both DEX treatment and E. coli
      challenge. These results suggest that stress-induced immunosuppression may be
      involved in the etiology of TOC, and that bacterial respiratory infection can
      lead to the development of TOC lesions.

PMID- 9603352
TI  - Research notes: ELISPOT assay for detection of antibody secreting cells to
      infectious bursal disease virus in chickens.
AB  - The ELISPOT assay was used to enumerate antibody secreting cells (ASC) in spleens
      of chickens infected with infectious bursal disease virus (IBDV). In the first
      experiment, chickens were orally challenged with IBDV. Spleens were collected 14
      d later and used for ELISPOT assay. The assay detected 16 to 28 IgG ASC per 10(6)
      splenocytes and 3 to 6 IgM ASC per 10(6) splenocytes. In the second experiment,
      chickens were vaccinated against IBDV and orally challenged with IBDV 14 d after
      vaccination. Spleens were collected 7 d postchallenge. The ELISPOT assay detected
      18 to 128 IgG ASC per 10(6) splenocytes and 4 to 6 IgM ASC per 10(6) splenocytes.
      The results indicated that the ELISPOT assay can be used to measure isotype
      specific antibody responses to IBDV or other avian pathogens.

PMID- 9603353
TI  - Effects and interactions of dietary levels of vitamins A and E and
      cholecalciferol in broiler chickens.
AB  - Four experiments were conducted to determine the effects and interactions of
      feeding different levels of vitamins A, cholecalciferol (vitamin D3), and E on
      broiler chicks. In Experiment 1, chicks were fed marginal vitamin D3 (500 IU/kg)
      and increasing dietary levels of vitamin A (5,000, 10,000, 20,000, 40,000,
      80,000, and 160,000 IU/kg). Bone ash was reduced by 10,000 IU/kg of vitamin A in
      the diet and at vitamin A levels above 20,000 IU/kg of diet body weight was
      reduced. In Experiment 2, two levels of vitamin A (1,500 and 15,000 IU/kg) and
      six levels of vitamin E (10, 500, 1,000, 2,500, 5,000, and 10,000 IU/kg) were
      added to the basal diet. High levels of vitamins A and E significantly (P <
      0.001) reduced bone ash. The vitamin A x E interaction was significant (P < or =
      0.05) for rickets. In Experiment 3, the same two levels of vitamin A as
      Experiment 2 and six levels of vitamin D3 (500, 1,000, 1,500, 2,000, 2,500, and
      3,000 IU/kg) were added to the basal diet that contained 10,000 IU/kg of vitamin
      E. Body weight and bone ash were increased by increasing vitamin D3 with a
      corresponding reduction (P < or = 0.05) in rickets. In Experiment 4, three levels
      of vitamin A (1,500, 15,000, and 45,000 IU/kg), three levels of vitamin D3 (500,
      1,500, and 2,500 IU/kg), and three levels of vitamin E (10, 5,000, and 10,000
      IU/kg) were added to the basal diet. Significant negative responses (P < or =
      0.05) to increasing dietary vitamin A were observed for bone ash, rickets, and
      plasma and liver vitamin E. A significant (P < 0.001) increase in bone ash and
      plasma calcium with a corresponding reduction in rickets was observed by
      increasing vitamin D3. Increasing dietary vitamin E adversely affected (P < or =
      0.01) bone ash, plasma calcium, and plasma and liver vitamin A concentrations.
      These results indicate the need for making feed with the proper ratios of
      vitamins A, D3, and E.

PMID- 9603354
TI  - Using acid insoluble ash marker ratios (diet:digesta) to predict digestibility of
      wheat and barley metabolizable energy and nitrogen retention in broiler chicks.
AB  - Routine bioassay measurements of AME or N retention of broiler diets require
      measurements of gross energy (GE) or N and an acid insoluble ash marker in diet,
      excreta, or ileal digesta. These measurements of GE and N are time-consuming and
      expensive in comparison to measurements of added or natural occurring levels of
      acid insoluble ash. Data from bioassay measurements of AME and N retention of 138
      wheat and 97 barley samples (with or without enzyme) were used to develop
      prediction equations relying on measurements of one that uses acid insoluble ash
      of diet, excreta or ileal digesta and GE and N of diet only; and a second
      equation using only acid insoluble ash of diet, excreta, or ileal digesta. The
      prediction equations demonstrate that part of or all of routine bomb calorimetry
      measurements for GE used to determine AME of wheat- or barley-based diets could
      be eliminated if a prediction error of 80 kcal/kg ME or less were acceptable. The
      prediction of N retention as compared to AME, based in part or totally on acid
      insoluble ash measurements, was less accurate; the prediction errors were equal
      to 2.3 and 6.5% for wheat- and barley-based diets, respectively. Ongoing research
      to improve the determination (speed, ease, and accuracy) of acid insoluble ash
      could provide a useful method to assess feeding value of ingredients and
      commercial poultry diets.

PMID- 9603355
TI  - Moderate excess of dietary protein increases breast meat yield of broiler chicks.
AB  - Two factorial experiments were carried out to evaluate the effects of dietary
      protein level, expressed as energy to protein (E:P) ratio, on yields of carcass
      and breast and on abdominal fat pad weight of male broiler chicks at 43 and 57 d
      of age. Two diets similar in their energy content and differing markedly in their
      protein content, in which the E:P ratios were lower and identical to the NRC
      (1994) recommendations, were used in Experiment 1. Four diets, the combination of
      two energy and two protein levels, in which the E:P ratios were lower and
      identical to the recommendations, were used in Experiment 2. There were no
      differences in feed intake or weight gain until 42 d of age between broilers fed
      the diets with the low and those fed the recommended E:P ratio. However, feed
      efficiency of the former was consistently and significantly (P < 0.05) higher.
      The high-energy diets did not affect feed intake but significantly improved
      weight gain between 7 and 28 d of age and feed efficiency until 42 d of age. In
      both experiments, carcass yield was not affected by dietary E:P ratio at 43 d of
      age; however, at 57 d of age it was increased significantly by the low E:P ratio
      in Experiment 1 and in birds fed the high energy diet in Experiment 2. On a
      factorial basis, the effect of the low E:P ratio on increasing yield was
      significant only in Experiment 1. The high dietary energy level increased carcass
      yield only at 43 d of age, but on a factorial basis its effect was significant.
      Carcass yield was significantly (P < 0.001) higher at 57 than at 43 d of age. In
      both experiments, breast meat yield was negatively correlated with dietary E:P
      ratio, a significant factorial effect. The difference in this variable between
      broilers fed the diets containing the low and the recommended E:P ratio was
      significant, at both ages in Experiment 1, and only at 57 d of age in Experiment
      2. Breast meat yield was not affected by dietary energy level, and it was
      significantly (P < 0.001) higher at 57 than at 43 d of age. Relative abdominal
      fat pad weight was increased significantly by increasing dietary E:P ratio.
      Dietary energy level and age did not affect this variable. The relationship
      between abdominal fat pad weight and breast meat yield within the treatments
      tended (in most of the cases not significantly) to be negative. However, this
      negative relationship was significant, at both ages, when the analysis was
      carried out with the pooled data at each age. It is concluded that the optimal
      E:P ratio for maximal breast meat yield for broiler chicks, particularly at 57 d
      of age, may be below the NRC (1994) recommendations.

PMID- 9603356
TI  - The effect of dietary protein level on the lysine and arginine requirements of
      growing chickens.
AB  - Comparisons were made of the growth and carcass fat responses to dietary lysine
      and of the lysine requirements of 1-wk-old broiler chickens receiving diets
      containing either 18, 20, 23 or 25% protein. Similar comparisons were made of the
      responses elicited by dietary arginine in diets containing 18 or 23% dietary
      protein. The responses to lysine supplementation and the lysine requirements of
      chicks receiving 23 or 25% protein diets were similar. In comparing the 18 or 20%
      to the 23% protein diet, the initial responses of growth and feed efficiency to
      dietary lysine were augmented, but the maximal weight gain diminished as dietary
      protein decreased, leading to a decrease in the lysine requirements. The amounts
      of extractable carcass fat or abdominal fat pad increased as dietary protein was
      lowered and, in general, were reduced either by lysine or arginine
      supplementation. Percentage of pectoral muscle increased slightly with dietary
      arginine and protein supplementation. The results suggest that when total dietary
      amino acid level is reduced, the requirements for the individual amino acid
      decrease due to growth retardation resulting from single or multiple amino acid
      deficiencies. Single amino acid supplementation of low protein diet is more
      effective in improving the amino acid balance than supplementation of high
      protein diets, resulting in a further decrease in the requirements.

PMID- 9603357
TI  - Requirement of the laying hen for apparent fecal digestible lysine.
AB  - A study was conducted to determine the requirement for lysine of a White Leghorn
      strain of hens with a body weight of approximately 1,600 g. Before starting the
      experiment, apparent fecal digestibility of amino acids of the basal diet was
      determined in an in vivo digestibility trial with six individually housed hens.
      The basal diet used was based on corn and soybean meal and contained 0.65% total
      and 0.49% apparent fecal digestible lysine. To the basal diet, seven graded dose
      levels (0.04, 0.08, 0.12, 0.16, 0.20, 0.24, and 0.28%) of lysine as L-Lysine x
      HCl were added. The experimental diets were fed for 12 wk, covering the early
      stage of laying from 24 to 36 wk of age. Each experimental diet was fed to 60
      individually caged housed birds. The dietary lysine requirement was found to be
      higher for maximizing efficiency of feed utilization than for obtaining maximum
      egg mass yield. Based on the feed conversion efficiency and at an egg mass yield
      of 57 g/hen-d, the requirement for total lysine was estimated to be about 900
      mg/hen-d. From the results of the digestibility trial, it was calculated that the
      estimated requirement for total lysine was equivalent to 720 mg apparent fecal
      digestible lysine per hen-day.

PMID- 9603358
TI  - Effects of amino acid restriction during starter and grower periods on subsequent
      performance and incidence of leg disorders in two strains of male large white
      turkeys.
AB  - Male turkeys of two commercial Large White strains (Nicholas 88, BUT 6) were
      subjected to growth restriction by means of reducing amino acid (AA) content of
      diets to a minimum of 75% of NRC (1994) suggested levels. There were three
      periods when diets containing 75% of NRC recommended AA for that age period were
      fed ad libitum: 0 to 3 wk, 0 to 6 wk, or 6 to 12 wk. A fourth (control) group was
      not restricted in AA content at any time. When turkeys were not fed the AA
      restricted diets they were fed diets formulated to meet a minimum of 100, 110, or
      120% of NRC (1994) AA recommendations, which resulted in a 3 x 4 factorial
      arrangement of treatments with three AA levels by four restriction times. Four
      pens of 12 males each were fed each AA by restriction time combination. At 18 wk,
      all birds were scored individually for leg condition and representative samples
      of turkeys were processed for parts yield. Birds fed restricted diets from 0 to 6
      or 6 to 12 wk had significantly lower BW at 18 wk than control birds. Birds fed
      the restricted diets from 0 to 3 wk did not differ significantly in 18-wk BW
      compared to control birds but the magnitude of difference was similar to that
      observed at the end of the restriction period. Feed utilization was not improved
      by early AA restriction. Restricting early growth resulted in a significantly
      higher incidence of birds with no leg disorders and a lower incidence of birds
      with moderate leg disorders than control birds. Feeding higher AA levels during
      realimentation resulted in a greater severity of leg disorders. Breast meat yield
      was depressed significantly as severity of early restriction increased.
      Increasing dietary AA above NRC (1994) recommended levels generally improved
      performance during realimentation but was not able to compensate for reduced
      gains during restriction.

PMID- 9603359
TI  - Research notes: Sodium bicarbonate supplementation in diets for guinea fowl
      raised at high environmental temperatures.
AB  - An experiment was designed to verify the effect of dietary NaHCO3 supplementation
      on performance of guinea fowl raised under high environmental temperatures (23.8
      to 33.9 C) and average relative humidity of 78.7%. One hundred and forty guinea
      fowl in their final period of growth (56 to 84 d of age) were allotted to
      individual wire cages. Five isocaloric (3,000 kcal ME/kg) 16% CP diets based on
      corn and soybean meal and containing 0, 0.6, 1.2, 1.8, and 2.4% sodium
      bicarbonate were fed to the birds. The experiment followed a randomized block
      design with 28 birds per treatment (14 of each sex) with each bird being
      considered as one repetition. Results showed that weight gain, feed intake, feed
      conversion, mortality, blood pH, carcass yield, and carcass composition were not
      affected (P > 0.05) by dietary sodium bicarbonate supplementation. Weight gain,
      feed intake, feed conversion, carcass moisture, and fat content, however, were
      significantly (P < 0.05) affected by sex. Females showed 17.49% better weight
      gain, 7.16% greater feed intake, and 9.6% better feed conversion than males.
      These differences were exacerbated at supplementation levels of 1.2 and 1.8%
      sodium bicarbonate in the diet. Male birds showed carcass moisture values
      significantly (P < 0.05) greater than those of female birds; the opposite
      occurred with carcass fat levels. The use of sodium bicarbonate in levels up to
      2.4% of the diet did not affect the performance of guinea fowl raised under the
      environmental conditions registered in this study.

PMID- 9603360
TI  - Sex identification of turkey embryos using a multiplex polymerase chain reaction.
AB  - A considerable portion of the W chromosome in Gallinaceous birds consists of
      tandem repetitive DNA. In the turkey, a 0.4-kb PstI element is repeated about
      10,000 times in the female diploid genome but is undetectable as such a unit in
      males. In this study a multiplex polymerase chain reaction was developed to
      identify the sex of turkeys based upon the PstI repeat. The technique utilized
      two pairs of primers, the first pair was designed to amplify a region of the PstI
      repetitive element, resulting in the production of a 177-bp fragment in females.
      The other pair was designed to amplify a region of the adenosine triphosphate
      (ATP) synthase gene, present in both males and females. The simultaneous use of
      all four primers in the same reaction resulted in the coamplification of a 177-bp
      and a 250-bp fragment in females and a 250-bp fragment in males. This technique
      was used to verify the sex of 45 adults of known sex and to identify the sex of
      74 embryos from Day 5 to hatch. This procedure is rapid and permits the sexing of
      many embryos in a short time. The ability to sex early embryos can facilitate
      studies on avian sex determination.

PMID- 9603361
TI  - The use of India ink and 51Cr-labeled microspheres in examining the function of
      the yolk stalk as a passageway between the yolk sac and intestine in posthatch
      broiler chicks.
AB  - India ink and radioactive 51Cr-labeled microspheres were used in separate trials
      to examine the role of the yolk stalk lumen as a distinct pathway between the
      yolk sac and gut through the first 5 d of posthatch growth in broiler chicks.
      Throughout this period, India ink was able to pass from the yolk sac through the
      yolk stalk and into the intestine, but was not able to pass from the intestine
      into the yolk stalk or yolk sac. Furthermore, labeled microspheres moved from the
      yolk sac via the yolk stalk into the gut; which caused the total counts per
      minute of the intestine, yolk stalk, and excreta to progressively increase. It
      was concluded that India ink and 51Cr-labeled microspheres were useful materials
      in establishing that the yolk stalk provides a direct one-way passage by which
      material in the yolk sac may move into the intestine of broiler chicks during the
      first 5 d after hatching.

PMID- 9603362
TI  - Sexual dimorphism in broiler chick embryos and embryonic muscle development in
      late incubation.
AB  - Studies were conducted to compare the weights and the characteristics of the
      Pectoralis superficialis, Semimembranosus, and Gastrocnemius of male and female
      chicken embryos at 16 and 20 d of incubation. Male embryos were significantly
      heavier than females at 16 d of incubation, but not at 20 d. The cross-sectional
      area of myofibers in the P. superficialis of 20-d-old female embryos was greater
      than that of males and the area of Semimembranosus myofibers was greater at 16
      and 20 d. The Semimembranosus apparent myofiber number of 16-d-old male embryos
      was greater than of females (P = 0.002). There was a significant increase in
      apparent myofiber number in this muscle between 16 and 20 d of incubation but
      there was no sex difference at 20 d. The number of Type I myofibers per 30,000
      microm2 area of the Gastrocnemius of 20-d-old male embryos was greater than that
      in females (P = 0.06). There were no significant sex differences in the protein
      concentration, DNA concentration, or protein:DNA ratio in the muscles at either
      age when data were pooled across the whole population. There were significant
      differences in these characteristics between sire families and in some sire
      families significant sex differences were noted. The protein:DNA ratio of the
      muscles increased between 16 and 20 d of incubation and the mitotic index
      decreased. These data suggest that the muscles of male embryos have more but
      smaller, myofibers than females, which may be responsible for the sex difference
      in embryo weight and provide the framework for the greater posthatching muscle
      growth.

PMID- 9603363
TI  - The effect of thermal preslaughter stress on the susceptibility of broiler
      chickens differing with respect to growth rate, age at slaughter, blood
      parameters, and ascites mortality, to hemorrhages in muscles.
AB  - In this study we investigated the occurrence of hemorrhages in four groups of
      electrically stunned broilers, differing with respect to growth rate, age at
      slaughter, hemodynamic parameters, and ascites mortality. In addition, the effect
      of three thermal preslaughter conditions on hemorrhage occurrence in thigh and
      breast muscles was studied. Broilers were either reared at a thermoneutral or low
      temperature regimen, and were either restricted in their feed consumption or
      consumed feed ad libitum. Prior to slaughter the broilers were exposed for 2 +/-
      0.5 h to either cold (4 +/- 2 C, RH 100%), moderate (19 +/- 2 C, RH: 70 to 80%),
      or warm (30 +/- 2 C, RH: 60 to 70%) conditions. There was no effect of rearing
      group, nor was there an interaction between rearing group and preslaughter
      condition on hemorrhage scores in the thighs or breasts. Preslaughter conditions
      only affected hemorrhage scores in the left thigh. Scores were highest in
      broilers exposed to moderate preslaughter conditions. These data indicate that
      the cause of hemorrhages in muscles is multifactorial. Hemorrhage severity was
      not diminished in broilers retarded in growth. Pathological hemodynamic
      adaptations to low rearing temperatures, leading to ascites, did not increase
      hemorrhage severity, neither upon exposure to moderate nor to cold or warm
      preslaughter conditions.

PMID- 9603364
TI  - Protein-to-film adhesion as examined by amino analysis of protein binding to
      three different packaging films.
AB  - A weak protein solution extracted from chicken breast meat was exposed to three
      types of packaging materials. The crude myofibrillar protein solution (12.0 mg
      protein/mL buffer) was suspended in a 0.6M NaCl/NaPO4 buffer, then placed in bags
      made from either polyethylene (nonbinding film), a nylon blend (binding film), or
      Surlyn (binding film). Two separate experiments were conducted to determine the
      effects of exposure time at a constant temperature and varying endpoint exposure
      temperatures on the amount of bound protein by amino acid analysis. Bound amino
      acids were quantified and grouped by class based on functional side group. It was
      theorized that differences in the amount of bound amino acid class was linked to
      the mechanism by which the meat-to-film binding occurs. The protein solution was
      sealed in bags and held in a water bath for 5 s, 20 min, 40 min, and 60 min at
      25.8 C for the timed experiment and heated from 25.8 C to 40, 55, 70, and 80 C
      for the temperature experiment. Protein adhesion occurred due to exposure of the
      solution to all films at 25.8 C. Greater protein adhesion was found in the two
      binding films than in the nonbinding film after 60 min of exposure. Heating the
      protein solution increased adhesion for the Surlyn film and showed a clear
      delineation in the degree of binding between the film types. Surlyn bound the
      most protein, followed by the nylon blend and then polyethylene. Bound protein
      increased in the Surlyn film with heating to 80 C, whereas the polyethylene did
      not show an increase in the amount of bound protein. Increases in binding
      observed between 55 and 80 C for Surlyn may be associated with transitional and
      conformational changes in muscle proteins that affect the adhesion of meat to the
      film surface.

PMID- 9603365
TI  - Broiler skin color as affected by organic acids: influence of concentration and
      method of application.
AB  - Color of broiler skin was evaluated after exposure to organic acids under various
      concentrations and simulated potential plant application conditions. Breast skin
      from chilled broiler carcasses was treated with acetic (AA), citric (CA), lactic
      (LA), malic (ML), mandelic (MN), propionic (PA), or tartaric (TA) acids at 0.5,
      1, 2, 4, and 6% concentrations. Each acid and concentration was applied in
      simulated dip (23 C for 15 s), scalder (50 C for 2 min), and immersion chiller (1
      C for 60 min) conditions. A tap water control was included with each application
      method. Objective color values of L* (lightness), a* (redness), and b*
      (yellowness) were measured before and after the treatments to calculate color
      differentials under a factorial arrangement of organic acids and concentrations.
      Skin lightness increased (P < 0.01) in simulated chiller as compared to dip and
      scalder applications. Skin redness was reduced significantly in scalder, and
      yellowness in dip and scalder applications, respectively. In simulated dip
      application, with the exception of PA, all acids decreased lightness and
      increased redness and yellowness values. Propionic acid had little affect on
      lightness and redness values, but decreased yellowness values. In simulated
      scalder application, with the exception of PA, all acids decreased lightness with
      increasing concentration. The redness values changed little in scalder
      application. However, yellowness values were increased with all acids, except for
      PA, which decreased yellowness values. In simulated chiller conditions, all
      acids, except for PA, decreased lightness and redness and increased yellowness
      values. Propionic acid increased lightness and decreased yellowness values
      significantly in chiller conditions. Alterations in skin color should be taken
      into account in the selection and application of organic acids as carcass
      disinfectants.

PMID- 9603366
TI  - Influence of time off feed on broiler viscera weight, diameter, and shear.
AB  - The influence of time off feed on broiler viscera weight, intestinal diameter,
      and shear was studied by subjecting market-age male broilers (42, 44, or 48 d) to
      incremental feed withdrawal periods (0, 6, 12, 18, or 24 h). Body weight was
      determined prior to feed withdrawal and at the time of processing. After
      slaughter, scalding, and defeathering, the abdominal cavity was opened. Diameter
      and shear of the proventriculus-ventriculus junction, jejunum, and ileum segments
      were measured, as were gallbladder length and width. Thoracic and abdominal
      viscera, liver, and ventriculus weights were determined, and liver surface color
      was measured. Percentage body weight loss increased with longer feed withdrawal
      periods, as viscera, liver, and ventriculus weights decreased. Gallbladder length
      increased with time off feed, whereas its width did not change. Diameter of the
      proventriculus-ventriculus junction, jejunum, and ileum decreased with longer
      feed withdrawal periods. Shear values for the proventriculus-ventriculus
      junction, jejunum, and ileum were not influenced by time off feed. Positive
      correlations (P < 0.05 and r > 0.4) between viscera weight and intestinal
      diameter were detected. Correlations between all measured parameters and shear
      values were not significant. Liver color measurements indicated that longer feed
      withdrawal periods resulted in significant linear decreases in L* (lightness),
      +a* (redness), and +b* (yellowness). Longer feed withdrawal periods decreased
      viscera weight and intestinal diameter, which would lower the potential for
      cutting the intestine during automated evisceration. However, the resulting
      greater gallbladder length (5 mm) would increase the possibility of bile
      contamination during evisceration.

PMID- 9603367
TI  - Sodium lactate affects sensory and objective characteristics of tray-packed
      broiler chicken breast meat.
AB  - The objective of this study was to determine the antimicrobial properties of
      sodium lactate solutions adjusted to various pH values. The effectiveness of
      sodium lactate increases with increased concentrations; however, there are off
      flavor development problems associated with increasing concentrations of sodium
      lactate above 2.0%. This study evaluated the effects of 2% sodium lactate
      treatments, adjusted to various pH values, on sensory characteristics,
      instrumental texture, and microbial populations of tray-packed broiler breast
      meat. Breast meat was treated with either tap water (pH 7.85) or 2% sodium
      lactate solutions (pH 7.30, 5.50, 5.00, 4.50, and 4.00) and stored at 2 +/- 1 C
      for 12 d. Approximately 15% of the panelists reported acidic aftertastes in
      samples treated with pH 5.00 sodium lactate solutions, and 10% of the panelists
      reported slight sodium or metallic off-flavor in all samples treated with sodium
      lactate. Instrumental texture measurements were similar (P > 0.05) for all
      treatments. Sodium lactate (pH 7.30 and 5.50) enhanced (P < 0.05) cooking yields
      and retarded the growth of spoilage bacteria (pH 5.50 and 5.00). Due to the
      development of severe discoloration and intense acidic off-odors and -flavors,
      testing was not conducted on samples treated with pH 4.50 and 4.00 sodium lactate
      solutions.

PMID- 9603368
TI  - Assessment of the protein quality of the smooth muscle myofibrillar and
      connective tissue proteins of chicken gizzard.
AB  - The objective of this study was to assess the protein quality of the myofibrillar
      and connective tissue proteins of chicken gizzard. Protein fractions were
      isolated from White Leghorn chicken gizzards and quantified by detailed amino
      acid analysis. This quantification involved repeated extractions of ground
      gizzards first with Triton X-100, then with low ionic strength imidazole-buffered
      saline (pH 7.1), followed by either 2% SDS or by 5 M guanidine hydrochloride. The
      total soluble intracellular protein fraction averaged 86.3% of the total protein
      and the insoluble extracellular connective tissue proteins comprised the
      remaining 13.7%. These fractions differed significantly in their essential amino
      acid (EAA) profiles, with the soluble intracellular fraction having the highest
      percentage EAA9 (48.6 to 49.0%) and the insoluble connective tissue fraction
      varying from 20.8 to 23%, compared to the FAO/WHO reference pattern value of
      33.9% for a 2- to 5-yr-old child. Calculated protein efficiency ratios (PER) for
      intracellular proteins averaged 3.02 compared with a value of 1.65 for the
      extracellular matrix proteins. These results provide an accurate assessment of
      the protein quality of smooth muscle proteins of chicken gizzard and may prove
      valuable for industrial control of the amount of connective tissue added to
      formulations of meats and poultry products.

PMID- 9603369
TI  - Descending auditory pathways in the adult male zebra finch (Taeniopygia guttata).
AB  - Here, we examine the connectivity of two previously identified telencephalic
      stations of the auditory system of adult zebra finches, the neostriatal "shelf"
      that underlies the high vocal center (HVC) and the archistriatal "cup" adjacent
      to the robust nucleus of the archistriatum (RA). We used different kinds of
      neuroanatomical tracers to visualize the projections from the shelf to the HVC.
      In addition, we show that the shelf projects to the cup and that the cup projects
      to thalamic, midbrain, and pontine nuclei of the ascending auditory pathway. Our
      observations extend to songbirds anatomical features that are found in the
      auditory pathways of a nonoscine bird, the pigeon (Wild et al. [1993] J. Comp.
      Neurol. 337:32-62), and we suggest that the descending auditory projections found
      in mammals may also be a general property of the avian brain. Finally, we show
      that the oscine song control system is closely apposed to auditory pathways at
      many levels. Our observations may help in understanding the evolution and
      organization of networks for vocal communication and vocal learning in songbirds.

PMID- 9603370
TI  - Integrin alpha1 localization in murine central and peripheral nervous system.
AB  - The distribution of neurons expressing integrin alpha1 subunit protein
      (INTalpha1) was examined in adult mouse tissues of not only the central nervous
      system, but also the sympathetic ganglia, and the adrenal gland by
      immunohistochemistry and immunoelectron microscopy. INTalpha1-positive neurons
      were observed in most tissues examined, and most of them were found to coexpress
      tyrosine hydroxylase (TH) except for Purkinje cells and hippocampal neurons.
      Expression of INTalpha1 was also observed in the malpositioned cortical neurons
      in reeler mutants, and appeared not to be affected by the aberrant cell migration
      of the reeler cortical neurons. In situ hybridization showed that the expression
      of INTalpha1 mRNA was correlated with synthesis of the INTalpha1 protein in each
      case, and this finding indicated that expression of the protein was controlled by
      transcriptional regulation of the INTalpha1 gene.

PMID- 9603371
TI  - GABAergic axon terminals at perisomatic and dendritic inhibitory sites show
      different immunoreactivities against two GAD isoforms, GAD67 and GAD65, in the
      mouse hippocampus: a digitized quantitative analysis.
AB  - Glutamic acid decarboxylase (GAD), the gamma-aminobutyric acid (GABA)-synthetic
      enzyme, consists of two isoforms, GAD67 and GAD65. Although distributions of the
      two GAD isoforms at the somatic level are known to be heterogeneous among
      different subpopulations of GABAergic neurons, those at the synaptic level have
      not been investigated. In order to analyze quantitatively the two GAD-isoform
      immunoreactivities in axon terminals, we combined confocal laser scanning
      microscopy with digitized image analysis to measure the gray levels of
      immunofluorescent signals for the two GAD isoforms in a large number of
      individual boutons in each hippocampal and dentate layer of the mouse. Synaptic
      boutons exhibited lamina-specific immunoreactivities against the GAD isoforms.
      Boutons in the principal cell layers (stratum pyramidale of the hippocampus
      proper and the granule cell layer of the dentate gyrus) showed more intense
      immunoreactivity against GAD67 than those in the dendritic layers (strata
      lacunosum-moleculare, radiatum, and oriens of the hippocampus proper and the
      molecular layer of the dentate gyrus). By contrast, boutons in the dendritic
      layers showed more intense immunoreactivity against GAD65 than those in the
      principal cell layers. Such differential distributions could be correlated to the
      GAD-isoform immunoreactivities in the axon terminals originating from parvalbumin
      containing neurons, a particular subpopulation of hippocampal GABAergic neurons
      mainly innervating the perisomatic domain of principal neurons. In addition to
      previously reported physiological and pharmacological differences between the
      GABAergic synapses on perisomatic domain and those on distal dendrites, the
      present results suggest a functional differentiation of GABAergic synapses
      between these two inhibitory sites.

PMID- 9603372
TI  - Light and electron microscopic study of neuronal nitric oxide synthase
      immunoreactive neurons in the rat subiculum.
AB  - Neurons in the rat subiculum that are capable of producing nitric oxide were
      studied by using an antibody to the neuronal isoform of nitric oxide synthase
      (nNOS). In the light microscope, the staining pattern with the nNOS antibody
      closely resembled that seen following histochemical processing with nicotinamide
      adenine dinucleotide phosphate diaphorase. Immunostained neurons were found in
      all layers, and, in addition, large dendrites in the apical dendrite layer were
      also immunopositive. Although a few immunolabelled cells had the typical
      morphology of interneurons, most were found to have the characteristics of
      pyramidal neurons. In the subiculum, these immunoreactive pyramidal neurons were
      concentrated mainly in the most superficial cell layers and closest to the CA1
      region, but pyramidal neurons in the CA1 layer of the hippocampus were
      consistently immunonegative. Immunopositive profiles in the subiculum were
      studied in the electron microscope and compared with unlabelled structures.
      Ultrastructural criteria suggest that both pyramidal and nonpyramidal subicular
      neurons are immunopositive for nNOS. Large, spiny dendrites and smaller, varicose
      dendrites were found to be immunoreactive for nNOS. Vesicle-containing profiles
      were probably presynaptic axons, and immunopositive boutons were seen to make
      symmetrical and asymmetrical synaptic contacts.

PMID- 9603373
TI  - Effects of whisker trimming on GABA(A) receptor binding in the barrel cortex of
      developing and adult rats.
AB  - Both sensory deprivation and blockade of gamma-aminobutyric acid A (GABA(A))
      receptors result in signs of cortical disinhibition. To investigate whether down
      regulation of GABA(A) receptors could underlie effects of sensory deprivation,
      [3H]muscimol binding was assessed in rat whisker barrels after chronic whisker
      trimming. Vibrissae in row C or rows A,B,D, and E were trimmed during certain
      developmental periods. When whiskers were trimmed for the first 6 postnatal
      weeks, [3H]muscimol binding was 8.3% lower in deprived barrel rows than in
      adjacent nondeprived rows (P < 0.001). The effect may be somewhat selective for
      GABA(A) receptors because there was no evident change in N-methyl-D-aspartate
      (NMDA) receptors as indicated by [3H]MK-801 binding. Ten weeks after whiskers
      were allowed to regrow, the decrease in [3H]muscimol binding was partly reversed
      (P < 0.002), leaving a 3.3% decrease (P < 0.001). These declines in GABA(A)
      receptors could contribute to persisting electrophysiological signs of reduced
      inhibition in similarly deprived barrel neurons (Simons and Land [1987] Nature
      326:694-697). A 6-week deprivation beginning in adulthood resulted in a 7.7%
      decrease (P < 0.001), indicating that the effect is not restricted to an early
      critical period. In rats trimmed for the first 10 postnatal days, [3H]muscimol
      binding declined 2.3% (P < 0.05), which is a small change compared with the
      magnitude of the developmental peak; thus, normal whisker input apparently is not
      required for the developmental increase in GABA(A) receptors. The present study
      suggests that sensory input can regulate cortical GABA(A) receptors in adulthood
      and during ontogeny. Down-regulation of cortical GABA(A) receptors may be a
      compensatory mechanism that serves to disinhibit the reduced sensory input.

PMID- 9603374
TI  - Nitric oxide synthase in the thoracic ganglia of the locust: distribution in the
      neuropiles and morphology of neurones.
AB  - Nitric oxide signaling is implicated in olfactory and visual pathways within the
      insect brain. In contrast, little is known about the distribution and function of
      nitric oxide synthase (NOS) in the ventral nerve cord. This study uses NADPH
      diaphorase histochemistry to describe the anatomy of NOS-containing neurones and
      the neuropilar distribution of NOS in the thoracic nerve cord of the locust. It
      is shown for the first time that mechanosensory neuropiles receive innervation
      from NOS-containing interneurones. Different cells innervate exteroceptive and
      proprioceptive projection neuropiles. In the projection neuropiles of tactile
      afferents, a dense meshwork of NOS-containing fibres is formed by collaterals of
      paired intersegmental axons that run through the entire thoracic nerve cord,
      innervating exclusively these exteroceptive neuropiles. In neuropile areas where
      proprioceptive afferents terminate, stained fibres are comparatively sparse and
      originate from local interneurones. The prothoracic ganglion showed strongly
      stained dense fibres in the dorsal neuropile that were not seen in the other
      neuromeres. This differential NOS-expression can be related to the branching
      pattern of a ventral group of neurones that was different in each neuromere. All
      thoracic neuromeres and the abdominal neuromeres A2 and A3 of the metathoraic
      ganglion contained a previously undescribed type of unpaired median neurone with
      bilaterally ascending and descending intersegmental projections that stained
      strongly for NOS. The distribution of NOS found in this study suggests a novel
      role for nitric oxide in an early stage of mechanosensory information processing
      in all thoracic neuromeres and an additional role in the prothoracic ganglion,
      which might be related to behavioural specializations of the forelegs.

PMID- 9603375
TI  - Localization of the clustering protein gephyrin at GABAergic synapses in the main
      olfactory bulb of the rat.
AB  - The tubulin-binding protein gephyrin is essential for the formation of
      postsynaptic glycine-receptor clusters in cultured spinal neurons. In addition,
      there is increasing evidence that gephyrin can also be present at nonglycinergic
      synapses. Here we analyzed immunocytochemically the subcellular localization of
      gephyrin in the main olfactory bulb of the rat and compared its distribution with
      that of gamma-aminobutyric acid (GABA) and of two major GABA(A)-receptor
      subunits. Gephyrin was selectively localized to the postsynaptic side of
      symmetric synaptic junctions, where the presynaptic terminals contained GABA.
      Moreover, gephyrin colocalized extensively with the alpha1 and gamma2 subunits of
      the GABA(A) receptor. In contrast, gephyrin was not detected at presumed
      glutamatergic synapses. These results indicate that gephyrin is not uniquely
      associated with glycine receptors, but can also be found at distinct GABAergic
      synapses. Thus, they raise the possibility that gephyrin is involved in anchoring
      certain GABA(A)-receptor subtypes in the postsynaptic membrane.

PMID- 9603376
TI  - Telencephalic connections in the Pacific hagfish (Eptatretus stouti), with
      special reference to the thalamopallial system.
AB  - The pallium of hagfishes (myxinoids) is unique: It consists of a superficial
      "cortical" mantle of gray matter which is subdivided into several layers and
      fields, but it is not clear whether or how these subdivisions can be compared to
      those of other craniates, i.e., lampreys and gnathostomes. The pallium of
      hagfishes receives extensive secondary olfactory projections (Wicht and Northcutt
      [1993] J. Comp. Neurol. 337:529-542), but there are no experimental data on its
      nonolfactory connections. We therefore investigated the pallial and dorsal
      thalamic connections of the Pacific hagfish. Injections of tracers into the
      pallium labeled many cells bilaterally in the olfactory bulbs. Other pallial
      afferents arise from the contralateral pallium, the dorsal thalamic nuclei, the
      preoptic region, and the posterior tubercular nuclei. Descending pallial
      efferents reach the preoptic region, the dorsal thalamus, and the mesencephalic
      tectum but not the motor or premotor centers of the brainstem. Injections of
      tracers into the dorsal thalamus confirmed the presence of reciprocal
      thalamopallial connections. In addition, these injections revealed that there is
      no "preferred" pallial target for the ascending thalamic fibers; instead,
      ascending thalamic and secondary olfactory projections overlap throughout the
      pallium. The mesencephalic tectum and tegmentum, which receive afferents from a
      variety of sensory sources, are interconnected with the dorsal thalamus; thus,
      ascending nonolfactory sensory information may reach myxinoid pallia via a tectal
      thalamic-telencephalic route. A comparative analysis of pallial organization
      reveals that the subdivisions of the pallium in gnathostomes (i.e., medial,
      dorsal, and lateral pallia) cannot be recognized with certainty in hagfishes.

PMID- 9603377
TI  - Isthmotectal connections in plethodontid salamanders.
AB  - In the plethodontid salamander species Plethodon jordani and Hydromantes
      italicus, the morphology and connectivity of isthmic cells were investigated by
      means of intracellular staining with biocytin. Dendritic arborization, axonal
      pathways, and size and morphology of telodendritic structures in the fiber layers
      of the optic tectum were determined. The latter were studied electron
      microscopically. The majority of isthmic neurons project to both tectal
      hemispheres, each cell forming telodendritic structures of different extent in
      the ipsilateral and contralateral hemisphere. These structures are column-like
      with diameters of about 60 microm. The ipsilateral terminals extend through
      layers 1-3 of the tectal white matter and intermingle with terminals of
      contralateral retinal afferents in layers 1-3, as well as with ipsilateral
      retinal afferents in layer 3. The corresponding contralateral telodendritic
      structures are confined to layer 1 and are not in direct contact with ipsilateral
      retinal afferents in layer 3. Both telodendritic structures are located in the
      rostral two-thirds of the optic tectum, which are binocularly innervated. The
      rostrocaudal and mediolateral sites of isthmic telodendra are in register with
      the direct retinal map in each tectal hemisphere. Few isthmic cells project to
      the caudal one-third of the optic tectum, which is monocularly driven. These
      cells form only one axonal terminal in the ipsilateral tectal hemisphere. Size
      and structure of these ipsilateral terminals are similar to the ipsilateral
      telodendra of bilaterally projecting isthmic neurons.

PMID- 9603378
TI  - Fellowship accreditation in cornea and external disease.

PMID- 9603379
TI  - Ocular allergy: the Third Annual Thygeson Lecture, presented at the Ocular
      Microbiology and Immunology Group Meeting, October 25, 1997.

PMID- 9603380
TI  - Superficial hypertrophic dendriform epitheliopathy post-keratoplasty.
AB  - PURPOSE: To describe a distinct and unusual superficial dendriform keratopathy
      that can be seen in postkeratoplasty eyes. METHOD: Three Caucasian women in their
      sixth decade of life were referred to the Corneal and External Disease Service at
      the University of California, Davis, and underwent penetrating keratoplasty for
      different diagnoses. After keratoplasty, hypertrophic dendriform epithelial
      lesions were observed. These were refractory to debridement as well as topical
      antibiotic and steroid combinations. Immunofluorescent antibody testing was
      performed in all cases to rule out herpetic infection, and the patients were
      treated with nonpreserved lubricants and medications to eliminate medication
      toxicity as the cause of the lesions. RESULTS: All three patients in this series
      developed raised, hypertrophic epithelial lesions after keratoplasty, which were
      refractory to therapy. Comfort and mild increase in visual acuity were restored
      with the use of thin, moderate water content therapeutic contact lenses.
      CONCLUSIONS: Superficial hypertrophic dendriform epitheliopathy is a distinct
      syndrome that occurs postkeratoplasty in patients with preexisting chronic ocular
      inflammation, tear dysfunction, and/or lid disease exacerbated by the toxic
      effects of postoperative topical medication.

PMID- 9603381
TI  - Retrospective analysis of a novel method of transscleral suture fixation for
      posterior-chamber intraocular lens implantation in the absence of capsular
      support.
AB  - PURPOSE: To determine the safety and efficacy of an alternative method for
      transscleral fixation of a secondary posterior-chamber intraocular lens (pcIOL)
      during penetrating keratoplasty. METHODS: Eighty-nine eyes that underwent
      secondary pcIOL implantation by using a modified transscleral suture-fixation
      technique during penetrating keratoplasty were retrospectively evaluated. The
      surgical technique used suture fixation to the surface of the sclera 5 mm
      posterior to the limbus, with the knot buried beneath Tenon's capsule and
      conjunctiva. Patient records were reviewed for postoperative complications,
      including suture erosion, pcIOL subluxation, vitreous hemorrhage, and retinal
      detachment. Mean follow-up was 24.4 months, with a range of 4-68 months. RESULTS:
      All eyes had successful fixation of their pcIOL immediately after surgery. Three
      (3.3%) eyes had graft failure. Six (6.7%) of 89 eyes showed evidence of suture
      erosion or partial exposure. Postoperative suture breakage occurred in two (2.2%)
      eyes. Posterior-segment complications included retinal detachment in one (1.1%)
      eye, vitreous hemorrhage in one (1.1%) eye, and limited choroidal hemorrhage in
      two (2.2%) eyes. Median visual acuity at 1-year follow-up was 20/70 (range, 20/25
      to light perception). CONCLUSION: This transscleral fixation technique provides a
      straightforward alternative to previously described techniques. Suture erosion,
      IOL dislocation, and posterior-segment complications occurred at relatively low
      rates compared with other pcIOL implantation techniques.

PMID- 9603382
TI  - Repeatability and agreement of two corneal-curvature assessments in keratoconus:
      keratometry and the first definite apical clearance lens (FDACL). CLEK Study
      Group. Collaborative Longitudinal Evaluation of Keratoconus.
AB  - PURPOSE: This study was conducted to determine the agreement and test-retest
      repeatability of two methods for measuring corneal curvature in keratoconus:
      keratometry and the First Definite Apical Clearance Lens (FDACL). Our interest in
      the FDACL procedure stems from the important contact lens-fitting information and
      documentation of disease progression provided by the FDACL trial lenses and
      observation of fluorescein patterns. METHODS: The Collaborative Longitudinal
      Evaluation of Keratoconus (CLEK) Study is an observational study that has
      enrolled 1,209 keratoconus patients to characterize the progression of
      keratoconus, to determine factors associated with its progression, and to assess
      its impact on quality of life. Ten percent of the patients were randomly selected
      at baseline for a retest examination. The baseline examination, which included
      keratometry and FDACL, was repeated in this sample. The FDACL is the flattest
      lens in the standardized CLEK trial lens set that vaults the apex of the cone.
      FDACL provides an estimate of the sagittal height of the cone. RESULTS: The
      correlation of FDACL with the steep keratometric reading (r = 0.89; p = 0.0001)
      and the flat keratometric reading (r = 0.83; p = 0.0001) were high. Test-retest
      repeatability as measured by the intraclass correlation coefficient (ICC) was
      high: FDACL ICC, 0.97; steep keratometric reading ICC, 0.96; and flat
      keratometric reading ICC, 0.95. Test-retest repeatability of FDACL remained high
      in advanced disease. CONCLUSION: FDACL provides a repeatable new procedure for
      determining disease severity in keratoconus.

PMID- 9603383
TI  - Etiology of immune stromal (interstitial) keratitis.
AB  - PURPOSE: We compared the etiologies of immune stromal keratitis (ISK), also known
      as interstitial keratitis (IK), in a recent group of patients with active and
      inactive ISK. METHODS: We reviewed the charts of 97 patients seen in the cornea
      clinic at the University of Minnesota from 1985 through 1994. Fifty-five patients
      were classified as having active ISK, defined by stromal inflammation without
      ulceration within 1 year of presentation. Forty-two patients were identified as
      having inactive ISK, defined by evidence of past stromal inflammation including
      stromal scarring, stromal thinning, ghost vessels, and reduplication of
      Descemet's membrane without active inflammation for the 1 year before
      presentation. We determined the etiology of the ISK by careful review of the
      patient's ocular examination, as well as medical and laboratory workup. Patients
      were labeled with the diagnosis of idiopathic ISK if no identifiable etiology was
      found. RESULTS: Herpes simplex virus (HSV) accounted for 71.4% of unilateral
      active ISK. Idiopathic accounted for 14.3%, and varicella-zoster virus accounted
      for 8.6% in this group. HSV was the etiologic factor of 50.0% of inactive
      unilateral cases, whereas 33.3% were idiopathic. Sixty percent of cases of
      bilateral, active ISK were from idiopathic causes. Syphilis was the cause of
      48.5% of bilateral inactive cases. In this group, 33.3% were from idiopathic
      causes. CONCLUSION: Although syphilis has been recognized for many years as the
      cause of 90% of cases of ISK, this is no longer true. We demonstrated that active
      ISK is most commonly caused by HSV or is idiopathic and that, although syphilis
      is the leading cause of inactive, bilateral ISK, it is responsible for only 18.6%
      of total cases.

PMID- 9603384
TI  - Comparison of ciprofloxacin and ofloxacin using human corneal susceptibility
      levels.
AB  - PURPOSE: We compared the in vitro susceptibility of gram-positive bacteria to
      ciprofloxacin and ofloxacin using human corneal susceptibility levels. METHODS:
      The concentrations of ciprofloxacin and ofloxacin that can be attained in 99% of
      human corneas (Cornea99) after topical administration were calculated
      statistically from reported data. The minimal inhibitory concentrations (MICs)
      were determined for 95 corneal isolates of gram-positive bacteria (51
      Staphylococcus aureus, 16 Streptococcus pneumoniae, 16 Streptococcus viridans
      group, and 12 coagulase-negative staphylococci). Susceptibility was interpreted
      by comparing the MICs with the respective Cornea99 for each antibiotic. Time-kill
      studies of representative gram-positive bacteria were tested using the Cornea99
      and the maximal corneal concentrations reported for ciprofloxacin and ofloxacin.
      RESULTS: The Cornea99 of ciprofloxacin and ofloxacin were calculated to be 3.57
      microg/ml (n = 22) and 2.22 microg/ml (n = 20), respectively. The reported mean
      corneal concentrations of ciprofloxacin (6.90 +/- 6.20 microg/ml) and ofloxacin
      (5.71 +/- 6.15 microg/ml) were comparable (p = 0.54). All gram-positive bacteria
      were equally susceptible to ciprofloxacin and ofloxacin (p = 0.54) based on the
      Cornea99. The time-kill studies determined that 8-24 h were required for both
      ciprofloxacin and ofloxacin to reach bactericidal levels. CONCLUSION:
      Ciprofloxacin and ofloxacin demonstrated comparable penetration into the cornea
      and provided equivalent in vitro efficacy against representative gram-positive
      bacteria. Time-kill studies indicated that 8-24 h of continual corneal
      concentrations of ciprofloxacin and ofloxacin were necessary in this study to
      reduce susceptible gram-positive bacteria by 99.9%.

PMID- 9603385
TI  - Homozygotic patient with betaig-h3 gene mutation in granular dystrophy.
AB  - PURPOSE: This study investigated patients with granular dystrophy and identified
      a homozygotic patient and his family with a mutation in the betaig-h3 gene.
      METHODS: Genomic DNAs were extracted from leukocytes of the peripheral blood of
      the proband, his parents, and his grandmother. All had granular dystrophy.
      Genomic DNAs from 50 unrelated normal volunteers were used as controls. Exon 4 of
      betaig-h3 gene was amplified and analyzed by direct sequence. Clinical data were
      collected. RESULTS: A single-base-pair transition was detected. This was a
      substitution of G to A of the second nucleotide position of codon 124 in the
      betaig-h3 gene that led to a replacement of histidine for arginine (Arg124His,
      CGC-->CAC). This mutation was the precise one previously reported for Avellino
      dystrophy. Although the proband was homozygotic for the mutant alleles, his
      grandmother, and parents were heterozygotic for these alleles. No sequence
      modification in the codon 124 from 50 nonaffected control individuals was
      detected. Clinical findings of the proband were severe. Keratectomies were
      performed for both his eyes 5 times for a 24-year period. His grandmother and
      parents showed mild clinical symptoms, had a few annular granules in the
      subepithelial stroma, and maintained good visual acuities. CONCLUSION: Arg124His
      mutation of the betaig-h3 gene was found in a pedigree with granular dystrophy.
      This mutation was the precise one previously reported for Avellino dystrophy.
      This fact shows an existence of Avellino form in Japanese. Homozygotic patient
      for mutant gene showed severe symptoms and an early onset.

PMID- 9603386
TI  - Efficacy of ophthalmic solutions to detach adhering Pseudomonas aeruginosa from
      contact lenses.
AB  - PURPOSE: To compare the efficacies of two all-in-one contact lens (CL) cleaning
      solutions and a detergent mixture on the detachment of a pathogenic bacterium
      adhering to two types of contact lenses in the absence and presence of a tear
      film. METHODS: Bacterial-detachment studies were carried out in a parallel-plate
      flow chamber. Rigid gas permeable (RGP) CLs with and without a tear film were
      fixed on the bottom plate of the flow chamber. After adhesion of Pseudomonas
      aeruginosa no. 3, bacterial detachment was stimulated by perfusing the system
      either with an all-in-one CL-cleaning solution, for soft contact lenses (SCL
      solution) and for rigid lenses (RCL solution), or with a detergent mixture of
      0.25% (wt/vol) sodium lauryl sulfate (SLS) and 0.2% sodium methyl cocoyl taurate
      (Tauranol). In addition, the all-in-one RCL-cleaning solution supplemented with
      0.025% (wt/vol) SLS and 0.02% (wt/vol) Tauranol was evaluated. A surface physical
      chemical analysis of the lenses before and after application of the solutions was
      done to determine whether remnants of the ophthalmic solutions or detergents
      could be found adsorbed to the CL surfaces. RESULTS: Both all-in-one CL-cleaning
      solutions stimulated minor bacterial detachment from CL surfaces with or without
      a tear film. The SLS/Tauranol detergent mixture, however, removed < or = 95% of
      the adhering P. aeruginosa cells, whereas the RCL-cleaning solution supplemented
      with detergents also stimulated significant detachment. Surface physical-chemical
      analysis clearly demonstrated the presence of a tear film on the CL surfaces, but
      remnants neither of the ophthalmic solutions nor of the detergents could be
      found. CONCLUSION: Ophthalmic solutions are not effective in stimulating
      detachment of adhering bacteria from CL surfaces. Supplementing of an all-in-one
      CL-cleaning solution with only small amounts of detergents yielded a solution
      much more effective in stimulating bacterial detachment while leaving no
      detectable remnants of the ophthalmic solution or of the detergents on the CL
      surfaces.

PMID- 9603387
TI  - Implantation of PHEMA keratoprostheses after alkali burns in rabbit eyes.
AB  - PURPOSE: We have previously examined histologically the healing of a PHEMA core
      and-skirt keratoprosthesis (the Chirila KPro) as a full-thickness implant in
      healthy animal corneas. The present study was carried out to determine whether a
      diseased cornea could also generate biocolonization of the skirt region of a
      KPro. METHODS: Ten KPros were placed as full-thickness corneal implants under
      conjunctival flaps in 10 alkali-burned rabbit corneas. Histological findings at
      intervals from 2 weeks to 6 months postoperatively were compared with earlier
      findings in 10 rabbits that had received identical KPros without prior alkali
      injury. RESULTS: Despite severe corneal injury and the reduced keratocyte
      population present, there were no clinically detected complications in 60%.
      Histological findings established that, compared with healthy host tissue, skirt
      biocolonization and KPro-cornea healing after an alkali burn were impaired, with
      evidence of epithelial downgrowth in 40%. One animal required euthanasia earlier
      than the planned end point, but no KPro extrusions occurred. CONCLUSION:
      Biocolonization of a KPro skirt is reduced but not prevented in an alkali-induced
      corneal inflammation model. Although no extrusions occurred, close follow-up and
      anticollagenolytic medication would be required to minimize the complication
      rate.

PMID- 9603388
TI  - Increased expression of fibrillin-1 in human corneas with bullous keratopathy.
AB  - PURPOSE: To characterize the expression of fibrillins, microfibril components, in
      human corneas with pseudophakic/aphakic (PBK/ABK) bullous keratopathy. METHODS:
      Normal and PBK/ABK corneas were stained by immunofluorescence for fibrillin-1 and
      -2. The expression of fibrillin-1 messenger RNA (mRNA) was studied by
      semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and
      Southern analysis. RESULTS: Only fibrillin-1 was detected in normal and diseased
      corneas. As described previously, in normal corneas, it was found in the limbal
      stroma and basement membrane (BM) and in the peripheral corneal epithelial BM for
      a short distance near the limbus. Central corneal BM, stroma, and Descemet's
      membrane were negative. All PBK/ABK corneas were positive for fibrillin-1, which
      was detected in fibrillar deposits at the endothelial face of Descemet's
      membrane, in the epithelial BM, subepithelial fibrosis areas, and posterior
      collagenous layer. By RT-PCR, low levels of fibrillin-1 mRNA were detected in
      normal corneas, and they increased significantly in PBK/ABK corneas. CONCLUSION:
      The deposition of fibrillin-1, together with tenascin-C, in PBK/ABK corneas may
      be part of an abnormal fibrotic/wound-healing process that occurs during the
      development of postsurgical corneal edema with the formation of bullae and
      posterior collagenous layer.

PMID- 9603389
TI  - Effects of PDGF on the migration of rabbit corneal fibroblasts and epithelial
      cells.
AB  - PURPOSE: We investigated the effects of human platelet-derived growth factor
      (PDGF) isomers on the migration of rabbit corneal fibroblasts and epithelial
      cells in the presence or absence of fibronectin (FN). METHODS: A modified
      Boyden's chamber method was used to detect cell migration. Cells placed in the
      inner chamber were incubated with PDGF in the outer chamber at 37 degrees C at 24
      h. In addition, epithelial cells were incubated in the presence or absence of FN.
      The migrated cells were stained and the cell number counted under a microscope.
      Checkerboard analysis was used to distinguish chemotaxis from chemokinesis.
      RESULTS: Natural PDGF and PDGF-BB enhanced the migration of corneal fibroblasts,
      whereas PDGF-AA did not. As for corneal epithelial cells, all the isomers of PDGF
      enhanced the migration, but only in the presence of FN, as in the absence of FN
      or at a low concentration gradient of FN, there was no enhanced cell migration. A
      checkerboard assay demonstrated that PDGF-BB had a chemotactic effect on the
      migration of corneal fibroblasts and epithelial cells, whereas PDGF-AA had a
      chemotactic effect on only corneal epithelial cells. CONCLUSION: These results
      suggest that PDGF is involved in corneal wound healing by stimulating the
      migration of corneal epithelial cells in the presence of FN and fibroblasts.

PMID- 9603390
TI  - Novel splice variants of human tenascin-C mRNA identified in normal and bullous
      keratopathy corneas.
AB  - PURPOSE: Pseudophakic/aphakic bullous keratopathy (PBK/ABK) human corneas
      accumulate an extracellular matrix glycoprotein tenascin-C (TN-C), an important
      modulator of cell adhesion and migration. Here, the purpose was to identify
      specific TN-C mRNA splice variants in normal and PBK/ABK human corneas. METHODS:
      Conventional and semiquantitative reverse transcription-polymerase chain reaction
      (RT-PCR) with primers to alternatively spliced (insertional) and constitutive
      fibronectin type II-like repeats of TN-C was used. Splice variants were
      identified by cloning and sequencing of RT-PCR products or by Southern blot
      analysis. RESULTS: The majority of corneal TN-C mRNA species corresponded to
      relatively small forms of the protein. Four previously unidentified TN-C mRNA
      splice variants were found in normal and PBK/ABK corneas that contained
      insertional repeats A1+A2+B+D, A1+A2+D, A1+B+D, or A1+D. Variants with
      insertional repeats A1+A2 or A1, previously described in mouse and rat, were also
      identified in human corneas. Semiquantitative RT-PCR showed that novel TN-C mRNA
      variants were dramatically elevated in PBK/ABK compared to normal corneas.
      CONCLUSION: TN-C protein was found in PBK/ABK but not in normal corneas; however,
      both normal and diseased corneas contained mRNA for 15 different TN-C isoforms.
      PBK/ABK corneas had elevated levels of six relatively small TN-C mRNA variants
      including five novel ones. These specific isoforms may adversely affect adhesion
      and migration of corneal cells thus contributing to the exacerbation of PBK/ABK.

PMID- 9603391
TI  - Bee sting of the cornea: a case report.

PMID- 9603392
TI  - Staphylococcal endophthalmitis following cataract extraction in a patient with
      Darier's disease.
AB  - PURPOSE: To report staphylococcal endophthalmitis following cataract extraction
      in a patient with Darier' s disease. METHODS: A 67-year-old man presented with
      decreased visual acuity OD and hypopyon 3 days status post-cataract extraction
      with intraocular lens placement. The patient was hospitalized and placed on
      topical and intravenous antibiotics. A diagnostic vitreous tap, pars plana
      vitrectomy, and intravitreal antibiotic installation were performed. RESULTS:
      Vitreal tap cultures indicated Staphylococcus epidermidis. His clinical status
      improved after vitrectomy and antibiotic therapy. The same bacteria was cultured
      from the patient's eyelids. CONCLUSIONS: The source of the S. epidermidis was the
      skin lesions on the patient's face and eyelids. Darier's disease is an
      exfoliative hyperkeratotic skin disease that affects all areas on the body except
      the buttocks. Although clean, sterile surgical techniques were followed, the risk
      of endophthalmitis following intraocular surgery in a patient with Darier's
      disease may be increased due to his or her dermatologic condition.

PMID- 9603393
TI  - Terrien's marginal degeneration associated with erythema elevatum diutinum.
AB  - PURPOSE: To describe a patient with Terrien's marginal degeneration associated
      with a chronic skin disease, erythema elevatum diutinum. METHODS: A 27-year-old
      woman with peripheral thinning of her left cornea associated with adjacent
      conjunctival and episcleral inflammation was clinically examined. RESULTS:
      Episodes of worsening skin lesions were associated with development of
      inflammation in her left eye. Administration of sulfones was effective for
      reducing both skin and ocular inflammation. CONCLUSION: Erythema elevatum
      diutinum should be considered an underlying systemic disease of Terrien's
      marginal degeneration.

PMID- 9603394
TI  - Is polyhexamethylene biguanide alone effective for Acanthamoeba keratitis?

PMID- 9603395
TI  - Pyoderma gangrenosum and necrotising sclerokeratitis.

PMID- 9603396
TI  - Reduction in the frequency of transplant-related complications in patients with
      chronic myeloid leukemia undergoing BMT preconditioned with a new, non
      myeloablative drug combination.
AB  - A radiation-free, non-myeloablative, myelosuppressive protocol, containing
      dibromomannitol and cytosine arabinoside, that remarkably reduced the frequency
      of transplant-related complications, such as veno-occlusive liver disease (VOLD),
      severe mucositis, bacterial sepsis, hemorrhagic cystitis, interstitial
      pneumonitis, has been applied in 19 CML patients, allotransplanted from identical
      siblings. Five patients were in accelerated phase. Acute GVHD developed in two
      patients and chronic GVHD occurred in 66% of patients. Follow-up was 3 to 7 1/2
      years. Although only eight patients were under 30 years of age, and only two
      patients had a history of less than 1 year, the leukemia-free survival was 82%.
      There were four hematological relapses. The reduction in post-BMT complications
      has greatly enhanced quality of life. The nurses reported significant reduction
      of work-load. Savings in eliminating the need for irradiation, parenteral
      nutrition, and several antibiotics are also remarkable. The remarkable reduction
      of certain transplant-related complications shows some advantage against
      busulphan-preconditioning.

PMID- 9603397
TI  - Analysis of peripheral blood CD34+ cells mobilized with granulocyte colony
      stimulating factor (G-CSF) using a long-term culture system.
AB  - G-CSF administered to healthy volunteers at a dose of 3 microg/kg for 5 days
      mobilized colony-forming units granulocyte-macrophage (CFU-GM), burst-forming
      units-erythroid (BFU-E), and long-term culture-initiating cells (LTC-IC) to a
      maximal level on day 4 or 5. To determine the number of primitive hematopoietic
      progenitors in the peripheral blood, mononuclear cells (MNCs) or CD34+ cells were
      cultured in a long-term culture (LTC) system. We defined the colonies produced by
      cells during LTC at week 2 as differentiated progenitors and those at week 5 as
      primitive progenitors. G-CSF administered to healthy volunteers increased the
      number of differentiated progenitors from day 4 and primitive progenitors on days
      3-5. Enriched CD34+ cells from healthy volunteers treated with G-CSF (PB-G) or
      without it (PB-SS), and patients treated with chemotherapy plus G-CSF (PB-CG)
      were subjected to LTC for 7 weeks. PB CD34+ cells from PB-G contained less
      primitive progenitors than those from PB-CG. Therefore, in healthy donors
      administered G-CSF at a dose of 3 microg/kg, the number of PB CD34+ cells should
      be harvested as much as possible to perform allogeneic peripheral blood stem cell
      transplantation (PBSCT).

PMID- 9603398
TI  - Flt 3 ligand, MGDF, Epo and G-CSF enhance ex vivo expansion of hematopoietic cell
      compartments in the presence of SCF, IL-3 and IL-6.
AB  - The aim of the study is to define the ability of Flt3 ligand, MGDF, Epo and G-CSF
      to modulate the expansion of different hematopoietic compartments in association
      with a basic cocktail of SCF + IL-3 + IL-6 (S36). CD34+ cells from normal bone
      marrow were cultured in stroma-free, serum-free medium for 10 days. Using various
      concentrations of cytokines, total cells could be expanded up to 5200-fold, CD34+
      cells up to 78-fold, CFU-GM up to 143-fold, BFU-E up to 46-fold, CFU-MK up to six
      fold and LTC-IC up to four-fold. The results were assessed by multiparametric
      analysis of variance. Three factors had a significant stimulatory effect on the
      late precursor compartment: Epo (P < 10(-5)), G-CSF (P=5 x 10(-3)) and FL (P=10(
      5)). Two were critical for CD34+ cell expansion: FL (P=4 x 10(-5)) and Epo (P=6 x
      10(-5)), while two were critical for BFU-E expansion: MGDF (P=8 x 10(-4)) and FL
      (P=0.017). FL strongly stimulated CFU-GM expansion (P < 10(-5)), whereas none of
      the growth factors studied had any effect on CFU-MK. FL (P=10(-4)) and MGDF
      (P=0.002) were essential to obtain high levels of expansion of LTC-IC as
      determined in limiting dilution assays. In the light of the above results showing
      a preferential effect on the expansion of precursor cells (3080-fold), CD34+
      cells (53-fold), CFU-GM (134-fold), BFU-E (46-fold) and LTC-IC (five-fold), the
      combination SCF, IL-3, IL-6, FL, MGDF, Epo and G-CSF was chosen as a putative
      cytokine cocktail for further studies on long-term culture. Sustained production
      of precursor cells, progenitor cells, LTC-IC and E-LTC-IC for up to 100 days
      reflects the persistence of very primitive stem cells. This suggests that these
      populations are probably able to undergo self-renewal divisions. The above
      combination of cytokines meets the required criterion for potential clinical
      application, which may be defined as an effective capacity to expand all cell
      compartments, using as the starting material high concentrations of low purity
      CD34+ cells.

PMID- 9603399
TI  - Monitoring soluble interleukin-2 receptor levels in related and unrelated donor
      allogenic bone marrow transplantation.
AB  - Acute graft-versus-host disease (GVHD) is effected by donor T lymphocytes which
      have been stimulated by host antigens. Activated donor T lymphocytes express
      interleukin-2 receptor (IL-2R), which is comprised of three subunits (alpha,
      beta, gamma). During activation, the a IL-2R subunit (CD25) is shed from the
      receptor complex and can be measured in the circulation. Soluble IL-2Ralpha (sIL
      2R) levels are increased in states of immune activation including GVHD, and could
      theoretically be used as a guide to therapy. Since IL-2Ralpha expression is an
      early marker of T cell activation, we investigated: (1) if an increase in sIL-2R
      is specific for acute GVHD; and (2) if serial sIL-2R levels can identify patients
      with early GVHD, prior to the onset of clinical tissue damage (effector
      function). Weekly sIL-2R levels were monitored in 36 patients undergoing matched
      related (n=23) or matched unrelated (n=13) allogeneic bone marrow transplantation
      (BMT). There was no significant difference in sIL-2R levels between matched
      related and matched unrelated recipients. Patients with acute GVHD (n=19, 53%)
      demonstrated higher sIL-2R levels, than those without during weeks 2 and 3 post
      BMT (P=0.02 and 0.04, Mann-Whitney U test, two-tailed). In patients with acute
      GVHD, the rise in sIL-2R preceded the clinical signs of GVHD (16/19 patients).
      However, patients with sepsis demonstrated a trend towards higher sIL-2R levels
      at week 1 and significantly greater levels by week 4 (P=0.02). Furthermore,
      patients with veno-occlusive disease (VOD) (25%) also had significantly higher
      sIL-2R levels at week 2 (P=0.03). We conclude that although sIL-2R levels
      increase in patients with acute GVHD, similar increases are seen in patients with
      VOD and/or sepsis and therefore, as a single biochemical marker, we find that
      serial measurements of sIL-2R lacks sufficient specificity to guide GVHD therapy.

PMID- 9603400
TI  - High-dose cyclophosphamide, etoposide and carboplatin with autologous bone marrow
      support for metastatic breast cancer: long-term results.
AB  - We report long-term results of high-dose cyclophosphamide, etoposide and
      carboplatin with ABMT in 20 patients with metastatic breast cancer. Median age of
      the group was 41 years, ECOG performance status = 0 in 18 patients and 1 in two
      patients. Twelve patients had received adjuvant chemotherapy. Predominant sites
      of metastases were lung (eight), chest wall (four), liver (four), bone (three)
      and lymph nodes (three). Response to pretransplant chemotherapy was complete (CR)
      in four patients, partial (PR) in 10 patients and stable (SD) in five patients.
      After high-dose chemotherapy eight patients were in CR, six PR, four SD and one
      progressive disease. Two patients died of regimen-related toxicities (candidal
      sepsis and alveolar hemorrhage). With a median follow-up period of 55 months
      (minimum 48 months), 12 patients have died of recurrent breast cancer, one died
      of toxicity of salvage chemotherapy, two are alive with disease, two are alive
      and free of progressive disease. One patient with relapsed disease was lost to
      follow-up. Median event-free survival is 6 months and median overall survival is
      17 months. All three of the long-term disease-free survivors had predominantly
      nodal disease. Two of these three patients presented with metastatic disease and
      received high-dose chemotherapy with ABMT as part of initial therapy for breast
      cancer; two of three attained CR to standard-dose cytoreductive therapy; none
      received doxorubicin-containing adjuvant chemotherapy.

PMID- 9603401
TI  - Autologous stem cell transplantation (ASCT) for poor prognostic Hodgkin's disease
      (HD): comparative results with two CBV regimens and importance of disease status
      at transplant.
AB  - Clinical outcome of 47 consecutive patients with advanced HD who underwent ASCT
      in our Department was analyzed retrospectively. Median age was 28 years (28 males
      and 19 females). At transplant, 15 (32%) patients were in CR (five in first CR
      after two chemotherapy regimens and 10 in second CR), eight (17%) in PR (seven
      without a prior CR), 22 (51%) had relapsing disease (19 with sensitive relapse)
      and two had primary refractory disease. The CVB regimen with two different
      schedules was used: 22 (47%) patients received standard CBV (CY 6 g/m2, BCNU 300
      mg/m2 and etoposide 600 mg/m2) and 25 (53%) received an increased CBV dose (CY
      7.2 g/m2, BCNU 440 mg/m2 and etoposide 2 g/m2). Antitumor response for 28
      evaluable patients was similar for both CBV regimens: 87 and 75% (P=0.39). At 7.2
      years, actuarial overall survival (OS), progression-free survival (PFS) and event
      free survival (EFS) for the whole series were 51.7+/-8%, 34+/-9% and 28+/-8%,
      with a median follow-up for the surviving patients of 3 years (0.7-7.6). No
      differences in these survival functions according to the CBV regimen used were
      observed (P=0.57). A history of a prior CR (P=0.003), duration of first CR >1
      year (P=0.04), absence of bulky nodal disease at transplant (P=0.054), absence of
      extranodal disease at transplant (P=0.01), and a CR status at transplant
      (P=0.0006) were associated with a better PFS on univariant analysis. On
      multivariate analysis, only CR status at transplant remained significant
      (P=0.05). When patients in second CR at transplant and those in first sensitive
      relapse were analyzed separately, no differences in clinical characteristics or
      in treatment received pretransplant were observed; however, PFS was significantly
      different (P=0.01). In conclusion, CR status at transplant is useful in
      identifying 'good risk' patients and is necessary to obtain the greatest benefit
      from ASCT independent of the CBV regimen used.

PMID- 9603402
TI  - Early intensive therapy with autologous stem cell transplantation in advanced
      Hodgkin's disease: retrospective analysis of 158 cases from the French registry.
AB  - This retrospective study was undertaken to evaluate cure rates, toxicity and late
      effects of early intensive therapy followed by autologous stem cell
      transplantation (ASCT) in patients with advanced Hodgkin's disease (HD). One
      hundred and fifty-eight cases of ASCT registered in the French database (SFGM)
      were retrospectively analyzed. Disease status at the time of ASCT was first
      partial response (PR) in 85, first complete remission (CR1) in 45 or primary
      refractory in 28 cases. The median time interval between diagnosis and ASCT was 7
      months (range 4-13). At the time of analysis in December 1995, 121/158 patients
      (76.6%) were alive, including 111 (70.2%) in continuous CR with a median follow
      up for surviving patients of 46 months (range 8-123). Peri-ASCT toxic death rate
      was 3%, and the actuarial risk of new malignancies was 4.9% at 5 years. The
      cumulative probability of 5-year overall survival (OS) was 75.2% for the entire
      group of patients, 80.6% for the chemosensitive ones, and 33.9% for the primary
      refractory (chemosensitive vs refractory, P < 0.0001). The cumulative probability
      of 5-year event-free survival (EFS) was 66.1% for the entire group of patients,
      73.7% for the chemosensitive ones, and 26.1% for the primary refractory
      (chemosensitive vs refractory, P < 0.0001). The only significant prognostic
      factor for both OS and EFS was disease status at the time of ASCT. Early ASCT in
      advanced HD is feasible, with a low risk of toxicity and without a higher rate of
      late effects compared with conventional treatment. Results achieved in
      chemosensitive patients at the time of transplantation lay the basis of future
      prospective randomized trials comparing ACST as front-line treatment to
      conventional treatment in high-risk cases.

PMID- 9603403
TI  - Megatherapy in children with high-risk Ewing's sarcoma in first complete
      remission.
AB  - To improve the prognosis of patients with metastatic or high-risk localized
      sarcoma in first CR, we explored the role of consolidation therapy with
      megatherapy and hematopoietic rescue. From 1986 to 1995, of 72 patients with
      Ewing's sarcoma from three pediatric departments, 30 were diagnosed as high-risk
      patients. Of these 30 patients, six did not achieve complete remission and four
      refused megatherapy and received multimodal treatment (chemotherapy + surgery
      and/or radiotherapy). The remaining 20 patients received megatherapy. There were
      15 males and five females with a median age of 10.8 years (range 2-18 years).
      Five patients had metastatic disease at initial diagnosis, nine patients had
      primary tumor in the pelvis and 13 had a tumor volume greater than 100 ml.
      Overall disease-free survival was 62.7+/-11%; 40+/-21.9% for those with
      metastatic disease, 76.2+/-12.2% for those with tumor volume greater than 100 ml
      and 64.8+/-16.5% for those with tumor in pelvic bones. In conclusion, megatherapy
      has improved the outcome of this group of patients relative to that expected
      following conventional therapy.

PMID- 9603404
TI  - Influence of ultraviolet-B irradiation on engraftment, graft-versus-host disease
      and graft-versus-leukemia effect in a rat model for allogeneic bone marrow
      transplantation.
AB  - Ultraviolet-B (UVB) irradiation is known to inhibit lymphocyte activity and
      consequently to reduce the incidence of graft-versus-host disease (GVHD) in
      experimental models for allogeneic bone marrow transplantation (BMT). GVHD is
      frequently associated with morbidity and mortality, but also with the beneficial
      graft-versus-leukemia (GVL) effect, demonstrated by a reduction in the incidence
      of leukemia relapse. In this study, we investigated whether UVB treatment of
      allogeneic T cells could prevent GVHD while sparing the beneficial GVL effect
      following allogeneic BMT in the Brown Norway myelocytic leukemia (BNML) rat model
      analogous to human acute myelocytic leukemia (AML). The dose of UVB required to
      abolish lethal GVHD in the rat allogeneic BMT model (WAG/Rij donors into BN
      recipients) was 4000 J/m2. However, this UVB dose simultaneously abrogated all
      GVL activity mediated by the T cells in the graft, while the radio-protective
      capacity of rat BM cells was strongly reduced. The number of allogeneic BM cells
      required to protect lethally irradiated BN rats was increased 50 to 100-fold. It
      is concluded that UVB acts as a non-selective form of T cell inactivation, and
      that UVB pretreatment of an allogeneic marrow graft is unlikely to be useful
      clinically as a preventive measure for GVHD, since other means of reduction of
      the number of functional T cells are less damaging to bone marrow stem cells.

PMID- 9603405
TI  - The levels of soluble P-selectin, von Willebrand factor and thrombomodulin in
      patients with neurological complications after allogeneic bone marrow
      transplantation.
AB  - We encountered two patients with uncommon neurological manifestations after
      allogeneic bone marrow transplantation (BMT), which occurred with rapid elevation
      of the leukocyte count at engraftment. Both patients then developed severe acute
      graft-versus-host disease (GVHD). To investigate the pathogenesis, we measured
      the levels of soluble P-selectin, von Willebrand factor (vWF) and thrombomodulin
      (TM), which reflect endothelial damage. The P-selectin, vWF and TM levels in the
      patients with (n=2) and without (n=5) neurotoxicity were, respectively, 168.5+/
      52.5 ng/ml vs 27.7+/-3.9 ng/ml, 6.7+/-0.15 FU/ml vs 3.42+/-0.41 FU/ml and 459+/
      37% vs 189.4+/-32.4% (mean+/-s.d.). All three parameters were much higher in the
      patients with neurological complications. These results suggest that
      neurotoxicity after BMT may be related to endothelial damage.

PMID- 9603406
TI  - Coagulation abnormalities and thrombotic microangiopathy following bone marrow
      transplantation from HLA-matched unrelated donors in patients with hematological
      malignancies.
AB  - Thrombotic microangiopathy is a well-known heterogeneous disorder that occurs as
      a complication of allogenic bone marrow transplantation (BMT). We evaluated 12
      consecutive patients receiving HLA-matched unrelated BMT and 12 consecutive
      recipients of HLA-identical related BMT for the development of bone marrow
      transplantation-associated thrombotic microangiopathy (BMT-TM) on days 30 and 60
      following BMT. A diagnosis was made in four of 12 (33.3%) unrelated compared to
      none of 12 (0%) HLA-identical cases. Levels of serum lactic dehydrogenase (LDH),
      fibrin degraded products (FDP) and de novo thrombocytopenia were elevated in
      eight of 12 patients (66.7%) receiving unrelated donor BMT, and none of the
      patients receiving related donor BMT. Our findings suggest clinical or
      subclinical microangiopathic changes may occur frequently in unrelated donor BMT.
      FDP elevation is possibly an important marker of microangiopathic changes as
      early complications of BMT.

PMID- 9603407
TI  - Luteinizing hormone-releasing hormone analogue: leuprorelin acetate for the
      prevention of menstrual bleeding in premenopausal women undergoing stem cell
      transplantation.
AB  - Prevention of uterine bleeding after stem cell transplantation was attempted in
      30 consecutive premenopausal women affected by hematological malignancies. This
      was with luteinizing hormone-releasing hormone (LHRH) leuprorelin acetate depot
      3.75 mg administered subcutaneously at least 30 days before the conditioning
      regimen and then 28 days after the first dose. Complete prevention resulted in
      all but one patient (96.5%) during the phase of profound thrombocytopenia. No
      side-effects related to leuprorelin were observed. All patients developed
      amenorrhea after transplantation. Gonadal function was periodically assessed by
      means of luteinizing hormone (LH), follicular stimulating hormone (FSH) and
      estradiol serum levels. Hormone levels were consistent with menopause in all
      patients. After transplantation, patients required hormone replacement with
      estroprogestinics or estrogens alone when indicated. Leuprorelin is highly
      effective in preventing uterine bleeding in premenopausal women undergoing stem
      cell transplantation and has an excellent toxicity profile and virtually no
      interface with hemostatic balance and hepatic function. The role of leuprorelin
      in gonadal protection is currently unclear and deserves further investigations.

PMID- 9603408
TI  - An unusual marrow transplant complication: cardiac myxoma.
AB  - We report a right atrial myxoma which suddenly developed in a thalassemic patient
      after allogeneic bone marrow transplantation. The tumor was first detected by
      echocardiography on day +47 after transplant and the patient underwent surgical
      removal of the myxoma on day +103. The post-operative course was uneventful, and
      at more than 3 years from the event, he is alive and well, cured from his
      congenital disease, with no detectable intra-cardiac tumor. The onset of the
      myxoma in the early post-transplant period and the extremely high velocity of
      growth suggest a possible relationship of this condition with the
      immunosuppressive status.

PMID- 9603409
TI  - Glutamine and vitamin E in the treatment of hepatic veno-occlusive disease
      following high-dose chemotherapy.
AB  - Hepatic veno-occlusive disease (VOD) of the liver is a common complication
      following high-dose cytotoxic therapy for bone marrow transplantation (BMT).
      Liver injury is believed to occur following free radical damage to endothelial
      cells of the sinusoids and small hepatic veins. Glutathione the main antioxidant
      of the cytosol becomes depleted following chemotherapy. Animal studies have shown
      that glutamine infusions can maintain glutathione levels and protect against free
      radical injury. We present two cases of established VOD successfully treated with
      intravenous glutamine (as dipeptide) and oral vitamin E. Although both cases have
      possible confounding factors we believe that these give support to the notion
      that glutamine/vitamin E may have a role in the prophylaxis and treatment of VOD.
      Further formal trials are indicated.

PMID- 9603410
TI  - Successful allogeneic bone marrow transplant for chronic myeloid leukaemia
      despite previous interferon-induced cardiomyopathy.
AB  - We report a patient with CML who developed a reversible dilated cardiomyopathy
      with cardiac failure following 10 months of IFN therapy. Despite the previous
      cardiomyopathy, he tolerated subsequent allogeneic BMT without any adverse
      cardiac events. Reversible IFN-induced cardiomyopathy should not be considered a
      contraindication to bone marrow transplantation.

PMID- 9603411
TI  - Hyperleukocytosis and retinal hemorrhages after chemotherapy and Filgrastim
      administration for peripheral blood progenitor cell mobilization.
AB  - A 49-year-old man with mantle cell lymphoma received 2.5 g/m2 of cyclophosphamide
      and 900 mg/m2 of etoposide followed by 10 microg/kg/day of Filgrastim for PBPC
      mobilization. This was complicated by marked hyperleukocytosis and retinal
      hemorrhages. The patient's symptoms improved gradually following leukopheresis.
      To the best of our knowledge, this is the first report describing this
      complication in patients undergoing PBPC mobilization. Early recognition of
      symptoms is important in order to stop Filgrastim and initiate immediate
      leukapheresis.

PMID- 9603412
TI  - Successful use of extracorporeal membrane oxygenation (ECMO) during BMT for SCID.
AB  - An 8-month-old girl with SCID presented with severe bronchiolitis. She received
      an HLA-identical sibling BMT without conditioning or GVHD prophylaxis. She
      deteriorated despite mechanical ventilation but had normal cardiac, hepatic and
      renal function. ECMO was instituted on day +3 and subsequent improvement was seen
      concurrently with emergence of CD4+ cells on day +11. She was taken off ECMO on
      day +18 and suffered a left-sided stroke evidenced by a dense left hemiplegia.
      She was extubated on day +25 and weaned from supplemental oxygen on day +36 and
      at day +100 has recovered strength in her extremities. This is the first
      successful use of ECMO as a bridge to engraftment in a BMT patient.

PMID- 9603413
TI  - Acquired autoimmune thrombocytopenia post-bone marrow transplantation for severe
      combined immunodeficiency.
AB  - Children with severe combined immunodeficiency (SCID) have profoundly diminished
      humoral and cellular immunity resulting in death during infancy unless immune
      reconstitution occurs by bone marrow transplantation (BMT). Thrombocytopenia post
      bone marrow transplantation can be seen in relation to infection, graft-versus
      host disease (GVHD) and rarely, as an autoimmune phenomenon due to immune
      dysregulation. We report two cases of severe AITP following BMT for SCID. Both
      cases developed large intracerebral hemorrhages from which one died. Autoimmune
      thrombocytopenia in this setting can be life-threatening and we recommend early
      and active intervention.

PMID- 9603414
TI  - Anticardiolipin antibodies and thromboembolism after BMT.
AB  - We describe a 4-month-old child who developed unusual thrombotic complications
      following allogeneic BMT for Omenn syndrome, a form of SCID. Eight weeks after
      the procedure the child suffered a major cerebrovascular accident and developed
      acute pulmonary hypertension in association with persistently elevated
      anticardiolipin antibody titres. It is postulated that central line-derived
      microemboli caused these serious thrombotic complications in the context of an
      evolving hypercoaguable state.

PMID- 9603415
TI  - Bone marrow transplantation in Shwachman-Diamond syndrome: report of two cases
      and review of the literature.
AB  - Patients with Shwachman-Diamond syndrome (SDS) have an increased frequency of
      myelodysplasia and leukemic transformation. We described two patients who
      received allogeneic stem cell transplantation and developed multiple
      complications, including seizure, hyperglycemia and renal tubular acidosis. A
      review of the literature showed that patients with SDS appeared to have an
      increased incidence of various transplant-associated problems. These patients
      frequently have underlying organ dysfunction and should be managed with extreme
      caution when treated with allogeneic stem cell transplantation.

PMID- 9603416
TI  - Secondary leukaemia characterised by monosomy 7 occurring post-autologous stem
      cell transplantation for AML.
AB  - Secondary leukaemia has rarely been reported as a complication of autologous stem
      cell transplantation for AML. We report two cases of AML who presented with well
      characterised cytogenetic abnormalities at presentation: t(8;21) and t(15;17)
      respectively, and who, after achieving complete morphological and cytogenetic
      remissions post-autograft, developed MDS/AML associated with monosomy 7. This
      secondary change is most frequently seen following alkylating agent therapy for
      solid tumours. The secondary leukaemia seen in our patients may thus be due to
      exposure of the residual stem cells to the alkylating agents used in the
      transplant conditioning.

PMID- 9603417
TI  - Bone marrow transplantation from a cadaveric donor.
AB  - A 2.5-year-old girl with neurogenic Gaucher's disease was transplanted with donor
      bone marrow from her HLA-compatible 12-year-old brother whose marrow was
      harvested 30 min post-mortem, after he suffered a severe head and neck injury.
      The marrow was stored in liquid nitrogen for 30 days prior to infusion. The post
      transplantation period was uneventful with good engraftment and no signs of graft
      versus-host disease. Currently, 6 months post-allogeneic bone marrow
      transplantation (alloBMT), analysis of both bone marrow and blood samples by PCR
      documented only cells of donor origin. This case demonstrates the feasibility of
      cadaveric marrow as a source of donor cells. To our knowledge, this patient is
      the only survivor of alloBMT from a cadaveric donor.

PMID- 9603418
TI  - Fatal chronic relapsing thrombotic thrombocytopenic purpura following autologous
      bone marrow transplantation for chronic myeloid leukemia.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a severe and potentially fatal
      syndrome increasingly reported shortly after allogeneic bone marrow
      transplantation. We report a 49-year-old patient who developed a recurrent and
      ultimately fatal form of TTP late after autotransplant for chronic myeloid
      leukemia.

PMID- 9603419
TI  - Paracrine and autocrine regulation of vascular endothelial growth factor during
      tissue differentiation in the quail.
AB  - The expression of vascular endothelial growth factor (VEGF) has been described to
      coincide both temporally and spatially with angiogenesis suggesting a role as a
      paracrine stimulator of endothelial cells. We have used digoxigenin labelled RNA
      probes to VEGF and the VEGF receptor-2 (Quek1) to investigate the relationship
      between VEGF expression and vascular events in quail embryos from day 1 to 13 of
      incubation. Furthermore, the effect of exogenously applied VEGF was studied in
      day 4 quail embryos using polyclonal anti-VEGF antibodies. Expression of VEGF
      mRNA was observed in day 1 and 2 embryos in regions of active angiogenesis and
      hemangiopoiesis. VEGF mRNA expression was found at high levels in the ventral
      aspect of the neural tube and Quek1 mRNA expression in the accompanying
      endothelial cells of day 3 embryos, suggesting a function in brain angiogenesis.
      However, in the neural tube, thyroid gland and cartilaginous skeleton VEGF mRNA
      was expressed at least 1 day before the ingrowth of vessels, suggesting that
      additional mechanisms are involved in control of angiogenesis. This is supported
      by the observation that application of VEGF165 into the midbrain induced
      dilatation of perineural vessels, while the intraneural vessels remained almost
      unaffected. Expression of VEGF mRNA was also observed at high levels in podocytes
      during all stages, indicative of its importance in glomerular development and
      function. The results of the present study indicate that as angiogenesis occurred
      in other tissues and organs (day 13 metanephros, dorsal third of the day 7 neural
      tube, skeletal muscle, and many mesodermal compartments), there was concurrent
      paracrine expression of VEGF mRNA and Quek1 mRNA. One noteable exception was the
      hepatocytes of the developing liver which appeared to remain VEGF-negative
      throughout the study. However, a small number of endothelial cells within liver
      sinuses, and additionally within the kidney and the elastic arteries, expressed
      VEGF mRNA. These results suggest that VEGF may also act as an autocrine mediator
      of angiogenesis, possibly as a result of localised tissue hypoxia.

PMID- 9603420
TI  - Differential progenitor dispersal and the spatial origin of early neurons can
      explain the predominance of single-phenotype clones in the chick hindbrain.
AB  - Clonal analysis of the chick embryo hindbrain has shown that during the first 48
      hr of neurogenesis the large majority of neural progenitor cells generate clones
      of neurons of only a single major phenotype or of only closely related
      phenotypes. This is despite considerable spatial intermixing of diverse neuronal
      phenotypes at these stages of development and suggests that phenotype may be
      decided early in mitotic precursors and remembered through several subsequent
      rounds of division and dispersal (Lumsden et al. [1994] Development 120:1581
      1589). Here we have used fate-mapping and clonal analysis to study
      neuroepithelial cell dispersal and mixing in the early hindbrain and discuss this
      data in relation to the generation of single phenotype neuronal clones. We find
      that dispersal is not uniform throughout the dorsoventral axis of the neural
      tube, but is highly dependent on position along that axis. Neuronal identity is
      related to the spatial origin and, hence, environment of the cell, and the
      spatial intermixing of diverse neuronal phenotypes at HH stage 20 is largely the
      result of circumferential neuronal migration as medially born branchial motor
      neurons migrate laterally while the more laterally born mlf neurons migrate
      medially. Constraints on the dispersal of clonally related progenitors, in
      particular those that lie adjacent to the floor plate, may serve to restrict the
      fate of these cells to the generation of only one major neuronal phenotype, i.e.,
      motor neurons.

PMID- 9603421
TI  - Collagen type IX and developmentally regulated swelling of the avian primary
      corneal stroma.
AB  - A critical event in avian corneal development occurs when the acellular primary
      stroma swells and becomes populated by mesenchymal cells that migrate from the
      periphery. These cells then deposit the mature stromal matrix that exhibits the
      unique features necessary for corneal function. Our previous work correlated the
      disappearance of collagen type IX immunoreactivity at stage 27 (5 1/2-6 days)
      with matrix swelling and invasion. To investigate further the mechanism of this
      disappearance, we employed immunohistochemistry after tissue fixation with
      Histochoice, a non-crosslinking fixative, immunoblot analysis of protein
      extracts, and gel substrate chromatography (zymography) to detect endogenous
      proteolytic activity. We found that corneas fixed in Histochoice retain
      immunoreactivity for type IX collagen for 1-2 days after corneal swelling. This
      immunoreactivity, however, becomes extractable from tissue sections of unfixed
      corneas at the time of initiation of stromal swelling and mesenchymal cell
      invasion. Immunoblot analysis confirmed that, following swelling,
      immunoreactivity for collagen IX decreased substantially in corneas, but not in
      the vitreous body, which served as a comparison. Analysis of ammonium sulfate
      (AS) fractions of such extracts indicated that, at the time of swelling, much of
      the immunoreactivity for type IX collagen in cornea shifted from the AS
      precipitate (containing high molecular weight molecules) to the AS supernatant
      (containing smaller fragments). In contrast, collagen IX immunoreactivity from
      the vitreous was precipitated by ammonium sulfate throughout the period of study.
      Collagen type II, a major fibrillar collagen in both the corneal stroma and
      vitreous, remained in the high molecular weight fraction at all times examined.
      Zymography detected the presence of the latent (proenzyme) form of gelatinase A
      (MMP-2) before corneal swelling and invasion (4 days), and both the latent and
      active forms of the enzyme after corneal swelling. This suggests tissue-specific,
      developmentally regulated proteolysis of collagen IX as a trigger for corneal
      matrix swelling.

PMID- 9603422
TI  - Differential preimplantation regulation of two mouse homologues of the yeast SWI2
      protein.
AB  - Epigenetic regulation of gene expression through modification of chromatin
      organization is an important mechanism in the development of eucaryotic
      organisms. We investigated the developmentally regulated expression of the mouse
      mBRG1 and mbrm genes, which are homologous to the yeast SWI2 gene. Both proteins
      are involved in chromatin remodeling as components of the mammalian SWI/SNF
      complex. The analysis was performed at a time in mouse development when the
      formation of a functional zygotic nucleus is closely linked to extensive
      chromatin modifications. Reverse transcription-polymerase chain reaction (RT-PCR)
      analysis in mature oocytes and through the first cleavage stages showed that both
      genes were highly expressed as maternal products but that they subsequently
      exhibited considerable differences in their level of expression when the
      transition to zygotic transcription occurred. Immunodetection of the two proteins
      with specific antibodies paralleled the RT-PCR analysis. The mBRG1 protein was
      present throughout preimplantation development, whereas zygotic mbrm was clearly
      detectable only when differentiation first occurs at the blastocyst stage. At
      this stage, mbrm was restricted to the inner cell mass. Cell type-specific
      expression of mbrm was also observed after in vitro differentiation of embryonic
      stem cells. These results indicate that the two murine homologues of SWI2 have
      substantially different roles in chromatin organization during the onset of
      embryonic development.

PMID- 9603423
TI  - G1-phase regulators, cyclin D1, cyclin D2, and cyclin D3: up-regulation at
      gastrulation and dynamic expression during neurulation.
AB  - Gastrulation in rodents is associated with an increase in the rate of growth and
      with the start of differentiation within the embryo proper. In an effort to
      understand the role played by the cell cycle control in these processes,
      expression of cyclin D1, D2, and D3--three major positive regulators of the G1/S
      transition--has been investigated by in situ hybrization and RT-PCR. Cyclin D1
      and D2 transcripts are first detected in the epiblast at gastrulation, when a
      proliferative burst occurs, and subsequently in its differentiated derivatives
      within the embryo proper, indicating that activation of their expression takes
      place prior to the differentiation of epiblast progenitors. In contrast, cyclin
      D3 transcript is undetectable in the epiblast itself and its expression is
      activated exclusively in extraembryonic tissues of both epiblast and trophoblast
      origin. During neurulation, expression of each cyclin D RNA is dynamically
      regulated along the anterior-posterior axis. In the hindbrain, cyclin D1 and D2
      show distinct segment-specific restricted expression and this pattern is
      conserved between mouse and chick. These results strongly suggest that D-type
      cyclins act as developmental regulators.

PMID- 9603424
TI  - Suppression of fibroblast growth factor 2 expression by antisense
      oligonucleotides inhibits embryonic chick neural retina cell differentiation and
      survival in vivo.
AB  - During retinal differentiation, fibroblast growth factor 2 (FGF2) expression
      increases in retinal neurons following the sequential appearance of the neuronal
      layers. The function of the developmental increase of endogenous FGF2 in the
      developing chick retina was investigated by using an antisense strategy, using
      both optic vesicle cultures and in ovo-intravitreal microinjections. The former
      model allowed us to study the consequences of FGF2 down-regulation on early
      ganglion cell differentiation, whereas, in the latter model, subsequent
      development stages and terminal maturation of the retina were studied. FGF2
      inhibition resulted in reduced ganglion cell differentiation, as visualized by
      the expression of the ganglion cell-specific RA4 and Islet-1 markers in optic
      vesicle cultures. Eyes intravitreally injected with the FGF2-specific antisense
      oligonucleotide exhibited profound retinal differentiation defects: thinning of
      the ganglion and outer nuclear (photoreceptors) cell layers and increased cell
      death in ganglion cell and inner nuclear layers. These results indicate that the
      loss of endogenous FGF2 cannot be compensated for in the retina and suggest that,
      although many other sources of FGF exist in the eye, the main role of the
      increase in endogenous FGF2 observed during retinal development is to
      intrinsically stimulate neuron differentiation and to protect neurons against
      cell death.

PMID- 9603425
TI  - Postgastrulation effects of fibroblast growth factor on Xenopus development.
AB  - We have investigated postgastrulation functions of FGFs in Xenopus development by
      the implantation of heparin beads soaked in FGF2 to various positions at various
      stages. Anterior implantations show different effects depending on whether they
      are made to early neurulae or to later stages. At stage 13-14 there is a total or
      partial suppression of anterior structures including the forebrain, eyes, and
      midbrain. From stage 15 onwards there is no loss of anterior parts but there is a
      change in the structure of the eye such that the neural retina remains continuous
      with the wall of the diencephalon and the territories normally forming the optic
      stalk and pigment epithelium instead become neural retina. Posterior
      implantations cause a disruption of somite segmentation without affecting the
      differentiation of muscle cells. This is associated with a prolongation of the
      uniform expression of X-Delta-2 during the phase of segmental determination.
      There is also an induction of ectopic otocysts, which can lie either ipsilateral
      or contralateral to the FGF-bead. The results are discussed in terms of the known
      late expression domains of the various Xenopus FGFs, and of the late functions of
      FGFs in higher vertebrates. They provide new evidence for a role of endogenous
      FGFs in the development of the eye, somites, and otocysts.

PMID- 9603426
TI  - Gscl, a gene within the minimal DiGeorge critical region, is expressed in
      primordial germ cells and the developing pons.
AB  - Gscl, a paired-type homeobox gene, has been implicated in the pathology of
      DGS/VCFS by virtue of its genomic location and its structural similarity to the
      Gsc gene family. Immunohistochemical and in situ studies were performed to
      examine the expression pattern of this gene during embryonic development. A
      polyclonal antibody, generated to the full-length protein and shown to be
      specific for GSCL by both Western blotting and immunofluorescence, was used for
      immunohistochemical localization. Both in situ and antibody staining localized
      GSCL expression to a cluster of cells in the pons region of the developing brain.
      This GSCL expression pattern showed partial overlap with that of Pax6. More
      detailed immunohistochemistry revealed the GSCL in primordial germ cells during
      migration from the epithelium of the hindgut and later as they colonize the
      developing gonads. GSCL was not detected in tissues affected in DGS/VCSF.

PMID- 9603427
TI  - Chicken winged-helix transcription factor cFKH-1 prefigures axial and
      appendicular skeletal structures during chicken embryogenesis.
AB  - The cDNA cFKH-1 encodes a chicken winged helix/forkhead domain transcription
      factor that presents a dynamic expression pattern during chicken embryogenesis.
      Transcripts accumulate predominantly in early paraxial mesoderm, developing
      somites, and within mesenchymal precursors of skeletal structures. cFKH-1 RNA is
      first detected in the developing mesoderm of HH stage 6 embryos. During
      subsequent development cFKH-1 RNA accumulates in a dorsal domain of the anterior
      presomitic mesoderm and later in all cells of the epithelial somites before it
      becomes limited to the sclerotome when somites compartmentalise. cFKH-1
      expression persists in the sclerotome, forming the vertebrae and in mesenchymal
      condensations in limb buds that will give rise later to the appendicular bones.
      In differentiated chondrocytes and definitive bone structures, however, cFKH-1
      expression is down-regulated. Additional expression domains are found in
      mesenchyme of branchial arches and the head, in the dorsal aorta, and weakly in
      the endocardium. Based on its expression pattern and the structure of the
      forkhead DNA-binding domain cFKH-1 constitutes a chicken relative to the murine
      family of fkh-1/MF1 and MFH-1 factors. The embryonic expression of the cFKH-1
      gene defines distinct mesodermal domains and suggests that it may regulate gene
      expression in mesenchymal cell lineages that will form cartilage in trunk and
      limb buds.

PMID- 9603428
TI  - Fate map of the developing chick face: analysis of expansion of facial primordia
      and establishment of the primary palate.
AB  - Developing facial primordia change shape substantially in stages leading up to
      primary palate formation. We investigated expansion of cell populations within
      each of the four facial primordia of chick embryos between HH-stages 20 and 28,
      by using DiI labelling. Populations of cells centred around the nasal pits in the
      upper face, the midline of the paired mandibular primordia in the lower face, and
      at sites of fusion contribute most to overall expansion. Abundant Msx-1
      transcripts are found in regions of high expansion, and Fgf-8 transcripts are
      seen in ectoderm associated with some of these regions. Many cell populations
      display preferential expansion along one axis. Maxillary and mandibular primordia
      cell populations expand along the proximodistal axis, whereas at the distal tip
      of the frontonasal mass, cell populations expand mediolaterally. Thus outgrowth
      occurs at the tips of mandibular and maxillary primordia, but at the base of the
      frontonasal mass. At regions where adjacent primordia abut each other, we found
      bidirectional movement of cells between primordia, unidirectional movement or
      could detect no movement at all. Regions of highest expansion in each primordium
      have the highest percentage of S phase labelled cells. Cell death occurs in some
      regions of low expansion but it seems likely that cell rearrangements and
      intercalations also contribute to shaping. These rearrangements could be
      associated with stretching of the primordia by neighbouring tissues. Treatment of
      chick embryos with retinoic acid causes clefts of the primary palate (Tamarin et
      al. [1984] J. Embryol. Exp. Morphol. 84:105-123). We found a decrease in
      expansion of cell populations that normally contribute to primary palate
      formation but surprisingly little ectopic cell death. Expansion of other cell
      populations in the treated upper face was more even rather than directed. This
      further supports the idea that tension exerted by neighbouring tissues plays a
      major role in global shaping of the upper face.

PMID- 9603429
TI  - Monoclonal antibody against adult marrow-derived mesenchymal stem cells
      recognizes developing vasculature in embryonic human skin.
AB  - We have described previously a monoclonal antibody (SH2) that specifically
      recognizes undifferentiated mesenchymal progenitor cells isolated from adult
      human bone marrow. These cells, which we operationally refer to as mesenchymal
      stem cells, have the capacity to differentiate and form distinct mesenchymal
      tissues such as bone and cartilage when the isolated cells are placed in the
      appropriate in vivo or in vitro environment. We report here the partial
      biochemical characterization of the antigen recognized by the SH2 antibody.
      Metabolically radiolabelled adult marrow-derived mesenchymal stem cells in
      culture were extracted and immunoprecipitated with the SH2 antibody. The purified
      antigen migrated as a single band of 90 kDa after sodium dodecyl sulfate
      polyacrylamide gel electrophoresis was performed under reducing conditions. The
      SH2-immunoprecipitated protein exhibited a molecular weight band shift after
      removal of N-linked oligosaccharides. We investigated the expression of the SH2
      antigen, along with the endothelial markers factor VIII-related antigen and Ulex
      europaeus I (UEA-I) lectin during specific developmental periods in human dermal
      embryogenesis and in the postnatal period through aged adults. Frozen sections of
      human embryonic, fetal, or postnatal skin ranging from 8 weeks estimated
      gestational age (EGA) through 84 years of age were immunostained or double
      immunolabelled with antibodies SH2, UEA-I, or factor VIII-related antigen
      followed by second antibodies with fluorescent markers. Positive cell surface
      reactivity with the SH2 antibody was seen in cells in the vascular plane in the
      earliest specimens (day 55 EGA) corresponding to the late cellular dermis period.
      During the period of the cellular to fibrous transition, in which the initiation
      of appendage development occurs, most SH2-reactive cells colocalized with
      vasculature markers UEA-I and factor VIII-related antigen, although there was a
      subset of cells recognized by SH2 antibody that did not colocalize with the
      endothelial markers. In contrast to the endothelial markers UEA-I and factor VIII
      related antigen, in which the number of immunopositive cells became more
      prominent with age and maturation of the dermis, the frequency of cells that
      contained the SH2-reactive antigen diminished with age. The SH2 reactivity
      evident in embryonic, fetal, and early postnatal periods was not observed in
      human skin specimens taken from adults greater than 30 years old. These
      observations support the hypothesis that the SH2 antigen is a cell surface marker
      of developing microvasculature and may play a role in dermal embryogenesis and
      angiogenesis.

PMID- 9603430
TI  - Isolation of the zebrafish homologues for the tie-1 and tie-2 endothelium
      specific receptor tyrosine kinases.
AB  - Several characteristics of the zebrafish embryo make it an attractive model in
      which to study the development of the cardiovascular system. The utility of the
      zebrafish as a model of mammalian vascular development will depend on the
      conservation of molecular and morphogenetic mechanisms of vessel growth. Here, we
      report the cloning of the zebrafish homologues of the endothelium-specific
      receptor tyrosine kinases tie-1 and tie-2. The Z tie-2 clone represents the first
      report of a full-length zebrafish endothelium-specific gene. The zebrafish tie
      family members have significant structural homology with their murine and human
      counterparts. In addition, like the murine tie-1 and tie-2 genes, expression was
      found predominantly in endothelial cells. At 24-hr postfertilization (HPF), Z tie
      1 was expressed in all observed populations of endothelial cells. Interestingly,
      Z tie-2 exhibited a similar, although slightly more restricted, expression
      pattern. Taken together, these data strongly suggest that mechanisms of vascular
      development are highly conserved across species and that zebrafish will continue
      to be a useful model for the investigation of vertebrate embryonic vascular
      development.

PMID- 9603431
TI  - Transcriptional interferences at the Hoxa4/Hoxa5 locus: importance of correct
      Hoxa5 expression for the proper specification of the axial skeleton.
AB  - We have previously described a Hoxa5 mutant mouse line in which specification of
      axial identity is perturbed and viability is markedly reduced. In the present
      study, we assay the Hoxa5 mutation in different genetic backgrounds and carry out
      a complete analysis of skeletal transformations. Although Hoxa5 is expressed over
      a large domain during embryogenesis, homeotic transformations of the axial
      skeleton are confined between cervical vertebra C3 and thoracic vertebra T2,
      which corresponds to the specific expression domain of the major Hoxa5
      transcript. Loss of Hoxa5 function also affects the formation of the acromion in
      the appendicular skeleton. Disruption of the adjacent Hoxa4 gene leads to similar
      homeotic transformations of the cervicothoracic vertebrae. To discriminate the
      respective role of each gene, we generated transheterozygous animals carrying
      inactivated Hoxa4 and Hoxa5 alleles on different chromosomes. Compound
      heterozygous mutants exhibit homeotic transformations in the cervicothoracic
      transition region more reminiscent to those observed in Hoxa5 homozygous mutants.
      Although the Hoxa5 mutation does not significantly affect Hoxa4 expression, the
      pattern of Hoxa5 expression is impaired in cis by the Hoxa4 mutation,
      specifically in the cervicothoracic region of the prevertebral column. The
      expression of Hoxa5 in this particular domain is also perturbed by the Hoxa5
      mutation itself, raising the possibility of regional autoregulation. Altogether,
      these results demonstrate the crucial role of Hoxa5 in the specification of the
      cervical and upper thoracic region of the skeleton and establish the importance
      of its correct expression for the proper patterning of the embryo.

PMID- 9603432
TI  - Three-dimensional analysis of the developing pituitary gland in the mouse.
AB  - Prenatal development of the mouse pituitary gland was analyzed in three
      dimensions by using confocal laser-scanning microscopy. In any wholemount
      preparation of the fetal pituitary gland from day 10 to day 18,
      immunofluorescence of laminin was observed in the deeper regions of the organ and
      demarcated the boundary of the epithelial tissue from the surrounding mesenchyme.
      Three-dimensional capillary networks in the fetal pituitary gland at day 13, day
      15, and day 18 were visualized clearly by perfusing the blood vessels with an
      fluorescein isothiocyanate-labelled gelatin solution. During days 12-14, cellular
      plates protruded from the anterior wall of the pituitary anlage and extended
      toward the base of the infundibulum. At the same time, the mesenchyme situated
      among the cellular plates separated from the surrounding mesenchyme except at the
      anteroventral portion of the anlage. In a posterior wall of the anlage,
      intercellular depositions of laminin were found among the epithelial cells, some
      of which reached the laminin sheet in the basement membrane of the anlage. From
      days 15-18, the pituitary gland enlarged, and the mesenchyme spread radially from
      the median anteroventral portion to the lateral, posterior, and dorsal regions
      and finally expanded throughout the entire organ. At the periphery, the
      mesenchyme in the pituitary gland connected with that surrounding the capsule.
      Laminin was still found in the intercellular spaces between the epithelial cells,
      and most of the intercellular depositions of laminin were combined with the
      laminin sheet in the epithelial basement membrane. An abundance of vessels
      entered the organ from its anteroventral portion, spread, and connected with one
      another throughout the gland, similar to the distribution of mesenchyme.
      Intercellular laminin would induce the polarization of the contacting epithelial
      cells, resulting in rearrangement of the epithelial cells. The mesenchyme might
      spread in the pituitary gland, providing the intercellular laminin a foothold, in
      order to cleave the epithelial cell mass into lobules. The development of
      capillary nets in the adenohypophysis corresponded well with that of the
      mesenchyme. Because laminin localizes mainly in the basement membrane in the
      fetal organs, immunostaining of laminin clearly indicates the boundary between
      epithelial tissue and the mesenchyme. Three-dimensional observation of laminin in
      wholemount preparation is very useful for studying morphogenesis.

PMID- 9603433
TI  - Molecular basis of type III hyperlipoproteinemia in Germany.
AB  - Type III hyperlipoproteinemia (HLP) is usually associated with homozygosity for
      apolipoprotein (apo) E2 (Arg112 --> Cys, Arg158 --> Cys). This common apo E
      isoform is defective in its binding to lipoprotein receptors. However, other rare
      mutations in the apo epsilon gene may also, in part dominantly, predispose to the
      disease. In order to assess the prevalence of rare apo E variants and mutations
      in the apo epsilon gene in Germany, we examined apo epsilon genotypes by
      restriction isotyping (RI) and apo E phenotypes by isoelectric focusing (IEF) in
      107 German patients with type III HLP. Concordance between apo epsilon genotype
      and apo E phenotype was observed in 101 subjects (94.4%). Six individuals (5.6%)
      had genotypes and phenotypes other than E2/2. One subject was apparently
      homozygous for apo E2 by IEF, but heterozygous for epsilon3/2 by RI. Sequencing
      of the apo epsilon gene disclosed a hitherto undescribed point mutation (TGG -->
      TGA) at the third position of the codon for amino acid 20 (Trp), introducing a
      premature termination codon. This is the first study demonstrating that in the
      German population type III HLP is mainly associated with homozygosity for apo E2
      (Arg112 --> Cys, Arg158 --> Cys) and that discrepancies between apo epsilon
      genotype and apo E phenotype are rare in this genetic condition.

PMID- 9603434
TI  - Haplotype analysis of two recurrent CDKN2A mutations in 10 melanoma families:
      evidence for common founders and independent mutations.
AB  - Germ-line mutations in CDKN2A have been shown to predispose to cutaneous
      malignant melanoma. We have identified 2 new melanoma kindreds which carry a
      duplication of a 24bp repeat present in the 5' region of CDKN2A previously
      identified in melanoma families from Australia and the United States. This
      mutation has now been reported in 5 melanoma families from 3 continents: Europe,
      North America, and Australasia. The M53I mutation in exon 2 of CDKN2A has also
      been documented in 5 melanoma families from Australia and North America. The aim
      of this study was to determine whether the occurrence of the mutations in these
      families from geographically diverse populations represented mutation hotspots
      within CDKN2A or were due to common ancestors. Haplotypes of 11 microsatellite
      markers flanking CDKN2A were constructed in 5 families carrying the M53I mutation
      and 5 families carrying the 24bp duplication. There were some differences in the
      segregating haplotypes due primarily to recombinations and mutations within the
      short tandem-repeat markers; however, the data provide evidence to indicate that
      there were at least 3 independent 24bp duplication events and possibly only 1
      original M53I mutation. This is the first study to date which indicates common
      founders in melanoma families from different continents.

PMID- 9603435
TI  - W474C amino acid substitution affects early processing of the alpha-subunit of
      beta-hexosaminidase A and is associated with subacute G(M2) gangliosidosis.
AB  - Mutations in the HEXA gene, encoding the alpha-subunit of beta-hexosaminidase A
      (Hex A), that abolish Hex A enzyme activity cause Tay-Sachs disease (TSD), the
      fatal infantile form of G(M2) gangliosidosis, Type 1. Less severe, subacute
      (juvenile-onset) and chronic (adult-onset) variants are characterized by a broad
      spectrum of clinical manifestations and are associated with residual levels of
      Hex A enzyme activity. We identified a 1422 G-->C (amino acid W474C) substitution
      in the first position of exon 13 of HEXA of a non-Jewish proband who manifested a
      subacute variant of G(M2) gangliosidosis. On the second maternally inherited
      allele, we identified the common infantile disease-causing 4-bp insertion, +TATC
      1278, in exon 11. Pulse-chase analysis using proband fibroblasts revealed that
      the W474C-containing alpha-subunit precursor was normally synthesized, but not
      phosphorylated or secreted, and the mature lysosomal alpha-subunit was not
      detected. When the W474C-containing alpha-subunit was transiently co-expressed
      with the beta-subunit to produce Hex A (alphabeta) in COS-7 cells, the mature
      alpha-subunit was present, but its level was much lower than that from normal
      alpha-subunit transfections, although higher than in those cells transfected with
      an alpha-subunit associated with infantile TSD. Furthermore, the precursor level
      of the W474C alpha-subunit was found to accumulate in comparison to the normal
      alpha-subunit precursor levels. We conclude that the 1422 G-->C mutation is the
      cause of Hex A enzyme deficiency in the proband. The resulting W474C substitution
      clearly interferes with alpha-subunit processing, but because the base
      substitution falls at the first position of exon 13, aberrant splicing may also
      contribute to Hex A deficiency in this proband.

PMID- 9603436
TI  - Identification of three novel mutations in human EYA1 protein associated with
      branchio-oto-renal syndrome.
AB  - The Branchio-oto-renal (BOR) syndrome is an autosomal dominant disorder
      characterized by branchial clefts, preauricular sinuses, hearing loss, and renal
      anomalies. Recent studies have shown that mutations in EYA1 are associated with
      BOR. However, the underlying molecular mechanisms by which mutations in the EYA1
      gene cause BOR syndrome are unknown. We have investigated 12 unrelated Caucasian
      families for mutations by heteroduplex analysis and direct sequencing of products
      from the polymerase chain reaction. In this study, we identified two novel
      frameshift deletions and a single base substitution that introduces a stop codon
      mutation in the C-terminal region of the EYA1 gene. No obvious relationships were
      observed between the nature of the mutations and the variable clinical features
      associated with BOR syndrome.

PMID- 9603437
TI  - A family with attenuated familial adenomatous polyposis due to a mutation in the
      alternatively spliced region of APC exon 9.
AB  - A family is presented with attenuated familial adenomatous polyposis of variable
      phenotype. The clinical features range from sparse right-sided polyposis and
      cancer in the proximal colon at the age of 34 to pan-colonic polyposis and cancer
      at the age of 68. Rectal sparing is common to all affected members. Heteroduplex
      analysis detected bands of altered mobility in exon 9 of the APC gene in all
      affected family members. Subsequently, a frameshift mutation was found in the
      alternatively spliced region of exon 9 at codon 398 which resulted in a stop
      signal 4 codons downstream. Alternatively spliced transcripts that delete the
      mutation were readily amplified from normal colonic mucosa and therefore create a
      mechanism for the attenuated phenotype seen in this family.

PMID- 9603438
TI  - Assessment of pyrin gene mutations in Turks with familial Mediterranean fever
      (FMF).
AB  - Familial Mediterranean fever (FMF) is an autosomal recessive disease clinically
      characterized by recurrent short self-limited attacks of fever accompanied by
      peritonitis, pleurisy, and arthritis and can lead to amyloidosis and renal
      failure in the longer term. It is prevalent mainly in non-Ashkenazi Jews,
      Armenians, Turks, and Arabs. Due to the lack of an accurate diagnostic test,
      patients often experience years of attacks and invasive diagnostic procedures
      before the correct diagnosis is made and adequate treatment is begun. Recently,
      the gene responsible for FMF, denoted pyrin, has been cloned, and three disease
      mutations have been described (French FMF Consortium, 1997; International FMF
      Consortium, 1997). In the current study we assessed the spectrum of mutations in
      this gene in 16 unrelated families of Turkish origin. The three previously
      reported missense mutations (Met-Ile at codon 680, Met-Val at codon 694, and Val
      Ala at codon 726) accounted for 29 of the 34 disease alleles. In one patient in
      whom no disease mutation was identified, the clinical picture was atypical enough
      to raise questions regarding the diagnosis. These results imply that the origin
      of FMF in Turkey is heterogeneous, that molecular diagnosis of FMF is possible in
      the majority of cases and clinically helpful, and that delineation of the
      undiscovered disease mutation(s) in the remaining cases remains a high priority.

PMID- 9603439
TI  - Molecular pathology of galactosialidosis in a patient affected with two new
      frameshift mutations in the cathepsin A/protective protein gene.
AB  - Galactosialidosis is a recessively inherited lysosomal storage disease
      characterized by the combined deficiency of neuraminidase and beta-galactosidase
      secondary to the genetic deficiency of cathepsin A/protective protein. In
      lysosomes, cathepsin A forms a high-molecular-weight complex with beta
      galactosidase and neuraminidase that protects these enzymes against
      intralysosomal proteolysis. In a patient affected with late infantile form of
      galactosialidosis, we found two new cathepsin A mutations, a two-nucleotide
      deletion, c517delTT and an intronic mutation, IVS8+9C-->G resulting in abnormal
      splicing and a five-nucleotide insertion in the cathepsin A cDNA. Both mutations
      cause frameshifts and result in the synthesis of truncated cathepsin A proteins,
      which, as suggested by structural modeling, are incapable of dimerization,
      complex formation, and catalysis. However, enzymatic assays, gel-filtration, and
      Western blot analysis of the patient's cultured skin fibroblast extracts showed
      the presence of a small amount of normal-size, catalytically active cathepsin A
      and cathepsin A-beta-galactosidase 680 kDa complex, suggesting that a low amount
      of cathepsin A mRNA is spliced normally and produces the wild-type protein. This
      may contribute to the relatively mild phenotype of the patient and illustrates
      the importance of critically comparing molecular results with clinical and
      biochemical phenotypes.

PMID- 9603440
TI  - Fluorescent chemical cleavage of mismatches for efficient screening of the factor
      VIII gene.
AB  - The detection of mutations in large and complex genes represents a practical
      challenge in research and diagnostic laboratories. Available methods are either
      time-consuming or lack sensitivity. Mutation detection in the factor VIII gene,
      responsible for haemophilia A, is hampered by its large size, its many exons, and
      the high frequency of de novo mutations that result in different mutations in
      unrelated patients. For an exhaustive analysis of mutations in the factor VIII
      gene, we established a nonradioactive screening method based on chemical cleavage
      of mismatches (CCM). PCR-fragments of approximately 1 kb were generated from
      genomic DNA (exon 14) or after reverse transcription from mRNA isolated from
      blood cells. Some modifications have been made to improve the CCM strategy.
      First, using a fluorescent tag, the method gains safety and flexibility. Second,
      fluorescent detection allows an accurate sizing of digested fragments when
      measured on an automated DNA sequencer. Third, by labelling both 5' ends of the
      PCR-fragment, the detection rate is virtually 100%. Finally, in the case of an X
      linked disease, samples from two patients can be mixed, which reduces the
      workload without losing information. In a pilot experiment, mutations were
      detected in 20 of 20 patients. In this series, three small insertions, two small
      deletions, one nonsense mutation, 13 missense mutations, and one splice mutation
      were found. Fifteen of these mutations are new. Thus virtually all kind of
      mutations are detectable by this method. Moreover, the analysis of the gene can
      be completed in 2 days.

PMID- 9603441
TI  - Approach to the management of bleeding esophageal varices: role of somatostatin.
AB  - Various treatment strategies have been used to control variceal bleeding,
      including drugs, esophageal tamponade, endoscopic sclerotherapy (ES), endoscopic
      variceal ligation, transjugular intrahepatic portosystemic shunt and emergency
      surgery. None of these procedures are ideal and treatment frequently requires a
      combination of techniques. Sclerotherapy is one of the most widely used methods
      to control variceal bleeding; however, success is largely dependent on an
      experienced endoscopist. Vasoactive drugs act by decreasing pressure and blood
      flow in the gastroesophageal collaterals and they offer the advantage of being
      administered by inexperienced personnel. Drugs currently used in the treatment of
      variceal hemorrhage include vasopressin, terlipressin, somatostatin and
      octreotide. In the clinical studies to date, somatostatin was more effective than
      vasopressin and as effective as terlipressin in the control of bleeding
      esophageal varices (BEV), with an improved safety profile. In contrast,
      octreotide has shown conflicting results and more data are required to support
      the drug in this indication. More recently the ABOVE (Acute Bleeding Esophageal
      Variceal Episodes) study has provided further evidence that early administration
      of vasoactive drugs such as somatostatin is significantly more effective than
      placebo in the overall control of acute BEV episodes in cirrhotic patients
      undergoing ES. Therefore, the administration of a vasoactive drug as early as
      possible before emergency sclerotherapy is recommended for the effective
      management of BEV.

PMID- 9603442
TI  - Re: Gerrow JD et al. Results of the National Dental Examining Board of Canada
      written examination and implications for certification. J Dent Educ 1997;61:921
      927.

PMID- 9603443
TI  - Application of the diligence inventory in dental education.
AB  - The fifty-five-item Diligence Inventory for Higher Education (DI-HE) was applied
      to a new subject group--190 dental students. After item and factor analysis, a
      fifty-item (four subscale) inventory best reflected this group. The DI-HE's split
      half reliability was 0.81 (p < 0.001), the reliability coefficient for the pre-
      and post-test was 0.68 (p < 0.01), and the correlation coefficient alpha was
      0.90. The DI-HE scores were high, with no statistical differences among the four
      classes. Overall, significant relationships were found between grade point
      averages (GPAs) and DI-HE total and subscale scores, with r values as high as
      0.44. While female students' DI-HE scores were significantly higher (p = 0.023)
      than male students' scores, no correlations between DI-HE scores and GPAs for
      females were found. The results suggest that DI-HE may be useful for assessment
      purposes in professional education.

PMID- 9603444
TI  - Review of current tenure policies and their relation to junior dental faculty.
AB  - The nature of tenure eligibility requirements for faculty has changed in recent
      years. The purpose of this study was to review the current tenure policies among
      U.S. dental schools. A five-page, sixteen-item survey was mailed to fifty-three
      U.S. dental schools. The survey produced thirty-seven completed questionnaires
      for a response rate of 70 percent. Among the results of the survey were: a) the
      most prevalent probationary period was seven years; b) faculty were expected to
      have a minimum of six to 15 publications to obtain tenure; c) only 39 percent of
      schools were perceived to offer a financial guarantee along with the award of
      tenure; and d) 69 percent of the schools offered an alternative track for
      selected full-time faculty.

PMID- 9603445
TI  - How competent do our graduates feel?
AB  - As part of a review of the undergraduate curriculum to assess its relevance for a
      future general practitioner, a survey of self-perceived competency at graduation
      based on the competency list developed by the Association of Canadian Faculties
      of Dentistry was circulated to recent graduates and the graduating class. The
      overall response was 67.5 percent, and revealed that approximately 70 percent of
      the respondents felt well prepared in approximately 69 percent of the
      competencies. These were the common "bread and butter" items of dentistry, such
      as basic restorative dentistry, examination, diagnosis, treatment planning, local
      anaesthesia, and scaling. Those areas reported as less well-prepared for included
      financial and personnel management, performance of soft-tissue biopsies, and
      management of chronic orofacial pain. Clarification of the raw survey results in
      focus groups was needed to uncover specific details that could lead to remedial
      action in problem areas.

PMID- 9603446
TI  - Trends in predoctoral education in geriatric dentistry.
AB  - Historically, education in geriatric dentistry has been limited in both quantity
      and quality. More recently, a number of educational initiatives have been
      developed in response to the growing number of older adults and their changing
      oral health status and dental treatment needs. A survey of U.S. and Canadian
      dental schools examined curriculum trends and assessed the effectiveness of
      educational initiatives and the value of AADS/AoA geriatric dental curricular
      materials. All schools responded. Compared to previous reports, more schools had
      geriatric didactic course(s), clinical rotations, and faculty with geriatric
      dental training. Fifty-eight percent of dental schools support geriatric
      dentistry in their budgets. The primary barriers to program expansion continue to
      be the lack of trained faculty members, a crowded curriculum, and fiscal
      concerns.

PMID- 9603447
TI  - Geriatric education in dental hygiene programs.
AB  - This study examined the current status of geriatric curricula in dental hygiene
      programs in both the United States and Canada and was comprised of a twenty-six
      item survey sent to dental hygiene programs. Responses (82 percent) revealed
      didactic requirements in 89 percent of programs and clinical requirements in 54.2
      percent of programs surveyed. Mean didactic clock hours were ten (+/- 8.2), while
      clinical clock hours were 21.8 (+/- 27.5). Specific geriatric courses were found
      in only 18.8 percent of programs, while 81.2 percent integrated geriatrics with
      other coursework. Both clinical (98.8 percent) and didactic courses (81.5
      percent) were taught primarily by dental hygiene faculty. Clinical experiences
      were primarily provided at extramural sites (79 percent). Half of schools
      surveyed (49.5 percent) felt their geriatric curriculum was less than optimal.
      The authors conclude that current levels of geriatric dental hygiene education
      may not meet the increasing demands of this growing population.

PMID- 9603448
TI  - Somatic mutation in autoantibody-associated VH genes of circulating IgM+IgD+ B
      cells.
AB  - Naive B cells expressing IgM and IgD on their surface have no or little somatic
      mutations in V genes. We have demonstrated that the human IgM+IgD+B cell clone (0
      81), which expresses nephritogenic idiotypes, produces IgM anti-DNA antibodies
      which show monospecificity to DNA. Using a DNA probe which specifically links to
      the VH gene of antibody 0-81, we identified the counterpart germ-line V gene of 0
      81, V3-7, which appears to be used by pathogenic autoantibodies in humans. Clone
      0-81, which may belong to naive B cells in terms of cell phenotype, uses a
      somatically mutated V3-7 gene. We further studied DNA sequences of V3-7 genes in
      circulating IgM+IgD+B cells from normal subjects and patients with systemic lupus
      erythematosus (SLE). The results revealed that rearranged V3-7 genes in IgM+IgD+B
      cells from patients with SLE contained somatically mutated sequences at
      significantly increased frequencies. These data indicate an abnormal maturation
      of B cells in autoimmune states that may be associated with an escape of self
      reactive B cells from the elimination process in the germinal center.

PMID- 9603449
TI  - The Ick protein tyrosine kinase is not involved in antibody-mediated CD4 (CDR3
      loop) signal transduction that inhibits HIV-1 transcription.
AB  - Monoclonal antibodies (mAb) that bind to the immunoglobulin CDR3-like region in
      the D1 domain of the CD4 molecule can inhibit the HIV-1 life cycle in CD4
      positive T cells and lymphoblastoid cell lines at the stage of transcription.
      This antiviral effect requires the integrity of the cytoplasmic tail of CD4 which
      is known to act as a signal transduction region through its association with the
      protein tyrosine kinase (PTK) p56lck. In this study, we investigated the putative
      role of this PTK in transducing inhibitory signals that act on HIV-1 replication
      after triggering by anti-CDR3-like region antibody treatment of infected T cell
      lines. CEM (CD4+/p56lck + inducible), MT2 (CD4+/p56lck - repressed), HSB-2 (CD4
      /p56lck + constitutively), HSB-2 WTCD4 (CD4+/p56lck + constitutively), HSB-2
      CD4.402 (CD4+ truncated form which lacks the cytoplasmic domain/p56lck +
      constitutively), and HSB-2 CD4mut (CD4+ unable to bind lck/p56lck +
      constitutively) were exposed to HIV-1 and cultured in medium supplemented with an
      anti-CDR3-like region-specific antibody or a control anti-CD4 mAb which does not
      inhibit HIV-1 transcription. We found that CDR3-loop-mediated inhibitory signals
      are efficiently transduced in CD4-positive cells which demonstrate a constitutive
      activation of p56lck or in CD4-positive cells lacking p56lck expression.
      Moreover, inhibitory signals were transduced in HSB-2 CD4mut cells expressing a
      cell surface CD4 with a double cysteine mutation in its cytoplasmic tail that
      renders the molecule unable to bind p56lck, but not HSB-2 CD4.402 cells
      expressing a truncated form of CD4 which lacks the cytoplasmic domain. These
      results indicate that the p56lck plays no direct role in this process and
      suggests the existence of another signaling partner for CD4.

PMID- 9603450
TI  - The 3' part of the immunoglobulin kappa locus of the mouse.
AB  - A detailed restriction map of a 430-kb contig comprising the single Ckappa, the 5
      Jkappa and the adjoining 22 Vkappa gene segments is presented. The first 12
      Vkappa genes following the JkappaCkappa region belong to the Vkappa21 family, the
      subsequent ones to the closely related families Vkappa8 and Vkappal 9/ 28.
      Previous difficulties in cloning all Vkappa21 genes can now be explained by the
      presence of a duplicated region in this part of the locus. The structure was
      established by analysis of yeast artificial chromosome, bacterial artificial
      chromosome and cosmid clones and by the so-called long template PCR technique.
      The distance between Ckappa and the proximal Vkappa21 gene is 22 kb and the
      average distances between the Vkappa genes are about 20 kb. Of the 12 Vkappa21
      genes 5 were sequenced for the first time and 8 of the 12 genes were found to be
      expressed. Of the 10 Vkappa8 and Vkappa19/28 germline genes 9 are new; expression
      products of 8 of the 10 genes were known. The known 5', 3' polarities allow to
      specify for the 22 Vkappa genes whether they are rearranged to the JkappaCkappa
      element by a deletion or an inversion mechanism. Also the formation of
      interesting rearrangement products in classical cell lines as MPC11, MOPC41 and
      PC 7043 can be explained now. The non-Vkappa sequence L10 whose rearrangement by
      inversion has been described earlier (Hoechtl and Zachau, Nature 1983. 302: 260
      263) was now localized downstream of JkappaCkappa.

PMID- 9603451
TI  - PMA/ionomycin induces Ig kappa 3' enhancer activity which is in part mediated by
      a unique NFAT transcription complex.
AB  - The Ig kappa 3' enhancer is required for high levels of Ig kappa gene expression.
      We now show that kappa 3' enhancer function increases five- to eightfold after
      stimulation of primary murine B cells with phorbol 12-myristate 13-acetate (PMA)
      and the calcium ionophore ionomycin. In the presence of cyclosporin A this
      induction is almost halved, suggesting that transcription factors of the NFAT
      family contribute to kappa 3' enhancer induction. Indeed, we identify a novel
      NFAT binding site which is required for full enhancer function. We find that this
      site is transcriptionally active in stimulated B cells, T cells and fibroblasts
      and that both PMA and ionomycin are required for maximal induction. Time course
      analysis of the components of the protein-DNA complex in primary lymphocytes
      reveals that both NFATp and NFATc are present in the complex after 15 min, while
      only NFATc is detectable after 4 h. This suggests that NFATc plays the dominant
      role in controlling long-term responses of this transcription factor family.
      Furthermore, JunB, JunD, FosB and cFos form part of the DNA-protein complex in
      Bal-17 B cells. Complex formation as well as transcriptional activity can also be
      induced by crosslinking of surface Ig. We have, thus, identified a unique NFAT
      complex in B cells that contributes to Ig kappa gene expression.

PMID- 9603452
TI  - Cyclosporin A increases IFN-gamma production by T cells when co-stimulated
      through CD28.
AB  - Despite its calcineurin-inhibiting properties, cyclosporin A (CsA) can not
      inhibit IL-2 production when T cells are co-stimulated by CD80/CD86 on the
      antigen-presenting cells. We studied the in vitro effect of CsA on IFN-gamma
      production. Anti-CD3 monoclonal antibody (mAb) was used as the primary stimulus
      for activation of purified human T cells. A stimulating anti-CD28 mAb, or CD80 or
      CD86 on stably transfected P815 cells, provided the co-stimulatory signal. IL-2
      production was hardly affected by CsA under these stimulating conditions, while
      IFN-gamma (at the protein and mRNA level) was markedly stimulated by CsA. The use
      of anti-CD3 or phorbol 12-myristate 13-acetate with ionomycin as the primary
      stimulus, together with costimulation through either CD28 or CD2 using
      transfectants with the appropriate ligands, allowed us to demonstrate that the
      resistance of IFN-gamma production to inhibition by CsA required both CD3 and
      CD28 triggering. Inhibition of IL-10 production, and to a lesser degree of IL-4
      production, by CD4+ cells was responsible for the enhancement of IFN-gamma
      production in the presence of CsA. In conclusion, IFN-gamma production by CD28-co
      stimulated CD4+ T cells is resistant to inhibition by CsA and can even be
      facilitated by CsA as a result of removing a negative regulatory signal which is
      mainly IL-10 mediated. This finding might have implications for immunosuppressive
      strategies based upon the use of CsA.

PMID- 9603453
TI  - Surface expression of TRAIL/Apo-2 ligand in activated mouse T and B cells.
AB  - Like other members of the TNF family, TRAIL/Apo-2 ligand induces apoptosis in
      sensitive target cells in a caspase-dependent fashion. We recently found that
      TRAIL may be constitutively expressed on the surface of mouse and human tumor
      cells of T and B origin. To define the pattern of TRAIL expression in normal
      immune cells, freshly isolated splenocytes, Concanavalin A/IL-2-activated T cells
      and lipopolysaccharide-activated B cells were analyzed by surface staining with
      or without secondary stimulation. Activated, but not resting, CD3+ cells
      expressed TRAIL in an activation-dependent fashion. Conversely, freshly isolated
      B220+ cells displayed surface TRAIL and CD95L that were retained following
      activation. Restimulation with the protein kinase C activator phorbol 12
      myristate 13-acetate and the calcium ionophore ionomycin or an agonistic anti-CD3
      monoclonal antibody induced significant up-regulation of surface TRAIL and CD95L
      in CD3+, TCRalphabeta cells with CD4+ or CD8+ phenotype. Similarly to CD95L,
      TRAIL up-regulation was protein synthesis dependent and cyclosporin A sensitive.
      These results indicate that both TRAIL and CD95L are displayed on the cell
      surface of activated immune cells and may thus represent complementary effector
      pathways in the regulatory functions of T and B cells.

PMID- 9603454
TI  - The myelin basic protein-specific T cell repertoire in Lewis rats: T cell
      receptor diversity is influenced both by intrathymic milieu and by extrathymic
      peptide presentation.
AB  - In the Lewis rat, the T lymphocyte response to guinea pig myelin basic protein
      (MBP) is focused almost exclusively on epitopes nested in the MBP peptide
      sequence p68-88, and is dominated by T cell receptors (TCR) using Vbeta8.2 gene
      elements, together with short N(D)N regions. Here we analyzed MBP-specific TCR
      from Lewis T cells differentiating in chimeric thymuses of Lewis rat/SCID mouse
      chimeras, in the absence of an intact rat thymic microenvironment (SCID(FL)
      mice). In these T cells, the TCR Vbeta repertoire is broad, N(D)N regions are
      significantly longer, and contain regular rates of template-independent N
      nucleotides. In striking contrast, a Vbeta8.2 biased TCR repertoire and few N
      region inserts are seen in p68-88-specific, Lewis rat-derived T cells
      differentiating in the complete rat thymic microenvironment provided by chimeric
      SCID mice bearing embryonic Lewis thymus grafts (SCID(FL/FT) mice). A T cell
      repertoire resembling the one in SCID(FL) mice is used by T cells of intact Lewis
      rats following immunization with a truncated epitope of MBP, p69-86. Also this
      selection generates a broad TCR Vbeta pattern with long N(D)N regions, and higher
      numbers of N nucleotides. These results show that both intrathymic repertoire
      selection, and extrathymic peptide priming exert profound effects on the TCR
      usage in the anti-MBP response of Lewis rats.

PMID- 9603455
TI  - IL-4-producing NK T cells are biased towards IFN-gamma production by IL-12.
      Influence of the microenvironment on the functional capacities of NK T cells.
AB  - NK T cells are an unusual T lymphocyte subset capable of promptly producing
      several cytokines after stimulation, in particular IL-4, thus suggesting their
      influence in Th2 lineage commitment. In this study we demonstrate that, according
      to the cytokines present in the microenvironment, NK T lymphocytes can
      preferentially produce either IL-4 or IFN-gamma. In agreement with our previous
      reports showing that their IL-4-producing capacity is strikingly dependent on IL
      7, CD4-CD8-TCRalphabeta+ NK T lymphocytes, obtained after expansion with IL-1
      plus granulocyte-macrophage colony-stimulating factor, produced almost
      undetectable amounts of IL-4 or IFN-gamma in response to TCR/CD3 cross-linking.
      However, the capacity of these T cells to produce IFN-gamma is strikingly
      enhanced when IL-12 is added either during their expansion or the anti-CD3
      stimulation, while IL-4 secretion is always absent. A similar effect of IL-12 on
      IFN-gamma production was observed when NK T lymphocytes were obtained after
      expansion with IL-7. It is noteworthy that whatever cytokines are used for their
      expansion, IL-12 stimulation, in the absence of TCR/CD3 cross-linking, promotes
      consistent IFN-gamma secretion by NK T cells without detectable IL-4 production.
      Experiments in vivo demonstrated a significant upregulation of the capacity of NK
      T cells to produce IFN-gamma after anti-CD3 mAb injection when mice were
      previously treated with IL-12. In conclusion, we provide evidence that the
      functional capacities of NK T cells, which ultimately will determine their
      physiological roles, are strikingly dependent on the cytokines present in their
      microenvironment.

PMID- 9603456
TI  - A lymphocyte-specific CC chemokine, secondary lymphoid tissue chemokine (SLC), is
      a highly efficient chemoattractant for B cells and activated T cells.
AB  - Secondary lymphoid tissue chemokine (SLC) is a CC chemokine expressed mainly in
      lymph nodes, appendix and spleen, and specifically chemotactic for lymphocytes
      (Nagira et al., J. Biol. Chem. 1997. 272: 19518-19524). Here, we carried out
      transendothelial migration assays to determine the classes and subsets of
      lymphocytes migrating toward SLC. SLC attracted freshly isolated B cells with
      high efficiency and T cells modestly. Thus, SLC is the first CC chemokine with a
      strong chemotactic activity on fresh B cells. Among T cell types and subsets, SLC
      broadly attracted CD4+ and CD8+ cells, CD45RO- (naive) and CD45RO+ (memory)
      cells, and CD26high (activated) and CD26low- (resting) cells. SLC also attracted
      both L-selectin+ and L-selectin- subpopulations of various T cell subsets and B
      cells. Furthermore, mitogenic stimulation strongly enhanced migratory responses
      of T cells and B cells toward SLC. By in situ hybridization, SLC mRNA was
      detected in the cortical parafollicular regions (the T cell areas) of a lymph
      node and an appendix. Collectively, SLC may be a basic chemokine supporting
      homeostatic migration of a broad spectrum of lymphocytes into the secondary
      lymphoid tissues. SLC may also be involved in immune responses by inducing highly
      efficient migration of T and B cells following antigenic stimulation.

PMID- 9603457
TI  - MHC class II-associated invariant chain peptide replacement by T cell epitopes:
      engineered invariant chain as a vehicle for directed and enhanced MHC class II
      antigen processing and presentation.
AB  - Proteolysis of the invariant chain (li) leads to the generation of abundant MHC
      class II-associated invariant chain peptides (CLIP), which bind in the MHC class
      II binding groove via supermotifs in a manner similar to that of antigenic
      peptides. We have engineered an li vector with the capacity to express any
      antigenic peptide of interest instead of CLIP, for T cell stimulation. When
      peripheral blood mononuclear cells (PBMC) were pulsed with li hybrids encoding T
      cell epitopes of tetanus toxin or acetylcholine receptor, stimulation of T cells
      was dramatically enhanced compared to stimulation after priming with either the
      native or recombinant proteins. Site-specific insertion of antigenic sequences
      into the CLIP region promoted enhanced antigenicity of li hybrids which were
      shown to be processed intracellularly in a chloroquine-sensitive compartment.
      Naturally processed T helper epitopes were visualized directly on the surface of
      PBMC and identified as analogs of CLIP associated with MHC class II molecules.
      This novel li vector provides a flexible and efficient system for the delivery of
      defined peptide epitopes to T cells which might be useful in the development of
      specific vaccines and in the study of intracellular processing.

PMID- 9603458
TI  - Sequential production of IL-2, IFN-gamma and IL-10 by individual staphylococcal
      enterotoxin B-activated T helper lymphocytes.
AB  - Upon primary activation, T helper (Th) cell populations express different
      cytokines transiently and with different kinetics. Stimulation of naive murine
      splenic Th cells with the bacterial superantigen Staphylococcus aureus
      enterotoxin B (SEB) in vitro results in expression of IL-2, IFN-gamma and IL-10
      with fast, intermediate and slow kinetics, respectively. This first report of a
      functional analysis of cells separated alive according to cytokine expression
      shows that these cytokines are not produced by different Th cell subpopulations,
      but can be expressed sequentially by individual Th cells. Th cells, activated
      with SEB for 1 day and isolated according to expression of IL-2, using the
      cellular affinity matrix technology, upon continued stimulation with SEB later
      secrete most of the IFN-gamma and IL-10. Likewise, after 2 days of SEB culture,
      cells expressing IFN-gamma, separated according to specific surface-associated
      IFN-gamma as detected by magnetofluorescent liposomes, 1 day later secrete IL-10.
      Thus, individual Th1 cells can contribute to the control of their own IFN-gamma
      expression by sequential expression of first IL-2, supporting their
      proliferation, and later IL-10, down-regulating the production of IFN-gamma
      inducing monokines and limiting the pro-inflammatory effects of IFN-gamma.

PMID- 9603459
TI  - The nature of antigen in the eye has a profound effect on the cytokine milieu and
      resultant immune response.
AB  - The eye is endowed with a number of mechanisms that protect it from immune
      mediated injury. One such mechanism, termed anterior chamber-associated immune
      deviation (ACAID), evokes the antigen-specific, systemic down-regulation of Th1
      responses to antigen inoculated into the anterior chamber of the eye. ACAID has
      been correlated with the selective production of IL-10 by the antigen-presenting
      cells (APC) and the development of a cross-regulatory Th2-like response. A small
      subset of antigens do not induce ACAID, but instead provoke IL-12 and normal Th1
      immunity. Remarkably, all soluble antigens tested are capable of inducing ACAID;
      only cell-associated antigens do not induce ACAID. We hypothesized that the
      nature of antigen plays a decisive role in the resultant immune response. This
      hypothesis was tested with two well-characterized antigens, ovalbumin (OVA) and
      SV40 large T antigen (SV40 Lg T Ag). The soluble forms of OVA and SV40 Lg T Ag
      induced ACAID in both in vivo and in vitro models of the eye. In contrast, the
      particulate forms of these antigens, i.e. OVA passively absorbed onto inert latex
      beads (OVA-latex) and SV40 Lg T Ag expressed in two different cell lines, 99E1
      and SV-T2, did not induce ACAID in either in vivo or in vitro models of the eye.
      In addition, the cytokine profiles of ocular APC pulsed with OVA or OVA-latex
      showed that soluble OVA induced the production of IL-10, whereas OVA-latex
      induced the production of IL-12. These data suggest that the nature of the
      antigen in the eye, whether soluble or particulate, is a crucial determinant in
      the resultant immune response. Moreover, they suggest a mechanism in which
      soluble antigens preferentially induce the release of ACAID-inducing IL-10
      whereas particulate antigens preferentially induce the release of Th1-inducing IL
      12 by responding APC.

PMID- 9603460
TI  - CD28 co-stimulation is intact and contributes to prolonged ex vivo survival of
      hyporesponsive synovial fluid T cells in rheumatoid arthritis.
AB  - In rheumatoid arthritis (RA), T cells in the inflamed joint are considered to
      play a crucial role in the pathogenesis. However, despite the fact that synovial
      T cells have an activated memory phenotype, they are functionally suppressed upon
      combined CD3 and CD28 stimulation. Here, we analyzed the contribution of both CD3
      and CD28 to the hyporesponsiveness of synovial T cells in RA. In contrast to the
      low CD3 responsiveness of synovial fluid (SF) T cells compared to peripheral
      blood (PB) T cells, the CD28 co-stimulatory response was observed to be
      unaffected. Hyporesponsiveness of SF T cells has previously been associated with
      decreased levels of intracellular glutathione (GSH), an antioxidant and regulator
      of the intracellular redox state. Treatment of SF T cells with N-acetylcysteine,
      an antioxidant and replenisher of GSH, selectively improved CD3-induced
      responses, while leaving CD28 responsiveness unaffected. These data show that the
      CD3 pathway is highly sensitive to intracellular GSH alterations, whereas CD28
      responsiveness is relatively refractory. Furthermore, in support for a functional
      role of CD28 co-stimulation, it was demonstrated that CD28 ligation acted in
      synergy with the IL-2 receptor gamma chain signaling cytokine IL-15 in the
      enhancement of the ex vivo survival of SF T cells. These data indicate that CD28
      co-stimulatory capacity of SF T cells, in contrast to CD3 stimulation, remains
      intact despite an altered intracellular redox state. Thereby, CD28 stimulation
      may contribute to the persistence of T cells at the site of inflammation, which
      might be of relevance in the pathogenesis of RA.

PMID- 9603461
TI  - Development of T cell precursor activity in the murine fetal liver.
AB  - The generation of T cell precursors in the liver of murine embryos was studied.
      The total number of T cell precursors in the liver was measured in thymic organ
      cultures by a limiting dilution assay. Sixty T cell precursors were detected in
      the liver at day 11 of gestation. By day 12 the number of precursors showed a 20
      fold increase, half of which could be explained by in situ proliferation as
      ascertained by a fetal liver organ culture assay. By day 13 a further 2-3-fold
      increase was observed. Whereas the number of total liver cells continued to
      increase, that of T cell precursors declined in the following days, suggesting a
      massive exit of these cells after day 13. The capacity to generate a TCRB
      repertoire in the cells was evaluated by a PCR assay. T cell precursors in day 11
      fetal liver developed a TCRB repertoire at day 8 of culture. The cells from days
      12-15 developed an identically diverse repertoire by day 6, suggesting that day
      11 precursors are more immature than those of later days. A mechanism for
      yielding a single wave of T cell precursors in the fetal liver is discussed with
      a proposed model.

PMID- 9603462
TI  - Anaphylatoxin C3a but not C3a(desArg) is a chemotaxin for the mouse macrophage
      cell line J774.
AB  - Varying results have been published regarding the functional reactivity of
      different cell types, including human monocytes, to the anaphylatoxin C3a and its
      degradation product C3a(desArg). To further delineate the functions of C3a and
      C3a(desArg) on this cell type we used the murine macrophage (Mo) cell line
      J774A.1 which is known to respond to the anaphylatoxin C5a. J774 cells
      specifically bound fluorescein isothiocyanate-labeled recombinant human C3a
      (rC3a). The cells migrated along rC3a concentration gradients in a dose-dependent
      manner with an optimal concentration of about 3 nM (rC5a:7 nM) and a half-maximal
      effective concentration (EC50) of about 1.2 nM (rC5a: 2 nM). The degradation
      product rC3a(desArg) was devoid of chemotactic activity. mRNA for the recently
      cloned G protein-coupled mouse high-affinity C3a receptor (C3aR) was detected in
      J774 cells, suggesting that this receptor represents the binding site for C3a on
      J774 Mo. In support of the specific nature of C3a-stimulated cellular mobility,
      RBL-2H3 transfectants expressing the human C3aR were also shown to migrate along
      gradients of rC3a (optimal concentration about 8 nM; EC50 about 3.5 nM) whereas
      rC3a(desArg) was again inactive. In summary, our findings demonstrate for the
      first time a specific, receptor-mediated chemoattraction of cells of the
      monocytic lineage to the anaphylatoxin C3a which may contribute to the
      accumulation of Mo at sites of inflammation.

PMID- 9603463
TI  - Suppression of spontaneous uveoretinitis development by non-immunopathogenic
      peptide immunization.
AB  - BALB/c nude mice which are grafted with thymus tissue from fetal F344 rats
      beneath the renal capsule (hereafter referred to as TG nude mice) spontaneously
      develop uveoretinitis as well as other organ-localized autoimmune diseases.
      Active immunization with an interphotoreceptor retinoid-binding protein (IRBP)
      derived peptide, amino acids 518-529 (P518-529), induced rapid development and
      high incidence of uveoretinitis, whereas immunization with another amino acid
      fragment, 1182-1194 (P1182-1194), inhibited the disease process. P1182-1194- or
      P518-529-specific T cell lines were established from TG nude mice. Although both
      were of CD4+ type, P518-529-specific T cells expressed Vbeta8 TCR while Vbeta6
      expression was evident in the P1182-1194-specific cells. P518-529-specific T
      cells produced IL-2 and IFN-gamma, but not IL-4 or IL-10, whereas P1182-1194
      specific T cells produced IL-4 and IL-10, but not IL-2 or IFN-gamma Adoptive
      transfer of these peptide-specific T cells into naive BALB/c nude mice resulted
      in development of uveoretinitis only in the P518-529 case. Furthermore, mice
      receiving both T cell types simultaneously did not exhibit uveoretinitis. The
      results indicate that the amino acid fragment of IRBP, P518-529, is uveitogenic
      and immunogenic in TG nude mice and induces Th1-type T cells related to
      uveoretinitis, whereas the amino acid fragment 1182-1194 is immunogenic but not
      uveitogenic, inducing Th2-type T cells which are involved in inhibition of this
      pathological response in TG nude mice.

PMID- 9603464
TI  - Enforced expression of human bcl-2 in CD4+ T cells enhances human herpesvirus 7
      replication and induction of cytopathic effects.
AB  - The cytopathic effects (CPE) resulting from the infection of CD4+ T cells by
      human herpes-virus 7 (HHV-7) comprises two major mechanisms: generation of large
      polyploid cells, which eventually undergo necrotic lysis, and apoptosis,
      predominantly occurring in small mononucleated cells. To dissect the relative
      contribution of these two phenomena to the overall cytopathicity of HHV-7 in
      vitro, we have investigated the effect of acute HHV-7 infection on SupT1 CD4+ T
      cell lines stably transfected either with the bcl-2 anti-apoptotic gene or with
      the control vector. Overexpression of Bcl-2 protein by these cells was associated
      with a progressive decline of the total number of viable cells, and a relative
      increase of enlarged polyploid cell. Of note, the size of polyploid cells was
      significantly greater in SupT1 cells overexpressing bcl-2 than in cells
      transfected with the control vector. In addition, bcl-2 expression accelerated
      the kinetics of an acute spreading of HHV-7 infection, as determined by HHV-7
      specific indirect immunostaining revealed by either fluorescence microscopy or
      flow cytometry. Our results indicate that inhibition of apoptosis in HHV-7
      infected cultures greatly favors the process of polyploidization and represents a
      major mechanism to maximize viral transmission.

PMID- 9603465
TI  - Two B cell subpopulations have distinct recirculation characteristics.
AB  - This report describes two subpopulations of B cells in sheep. These
      subpopulations have distinct recirculation characteristics and tissue
      distributions. Phenotypically the populations are distinguished by their
      differential expression of the complement receptors, CD21 (CR2) and CD11b/CD18
      (CR3). CD11b+ B cells are surface (s)IgMhi, co-express CD11c but are L-selectin
      negative. They populate the splenic marginal zone but are absent from splenic and
      ileal Peyer's patch (IPP) follicles and both afferent and efferent lymph
      compartments. Fluorescent tracing experiments showed that the CD11b+ B cells are
      non-recirculating as they did not appear in lymph after intravenous inoculation
      but are restricted to the blood and spleen. The CD11b-negative population
      expresses a conformational determinant of CD21 that is recognized by the
      monoclonal antibody Du 2-74. These cells are sIgMlo and co-express L-selectin.
      They populate the splenic and IPP follicles, are absent from the splenic marginal
      zone and are the only B cells in afferent lymph, efferent lymph and all lymph
      nodes. Fluorescence tracing experiments showed that the CD21 B cells are
      recirculating cells with their entry into efferent lymph being detectable by 16 h
      and peaking at 24-30 h. These data suggest that there are at least two lineages
      of B cells in the sheep with different phenotypic, functional and recirculation
      characteristics.

PMID- 9603466
TI  - Somatic hypermutation of the T cell receptor V beta gene in microdissected
      splenic white pulps from HIV-1-positive patients.
AB  - Somatic mutation of rearranged immunoglobulin V genes occurs in germinal centers
      (GC), resulting in affinity maturation of the immune response. Rearranged T cell
      receptor (TCR) genes were thought to be excluded from this process despite
      similarities in their gene structure. Somatic mutations were found among TCR V
      alpha (TCRAV) chains of antigen-specific T cells localized in GC of mice. Here,
      somatically mutated TCR V beta 3 (TCRBV) chains are identified among
      microdissected splenic white pulps from HIV-positive individuals. Both the
      frequency and the nature of the base substitutions were found to be similar to
      those of mutated immunoglobulin VH genes. This was true for intrinsic mutations
      in the TCR framework regions as well as for mutations underlying selective
      pressures in the TCRBV5 gene segment. The concentration of mutations and a
      preference for replacement mutations in complementarity determining regions of
      expanded clones were indicative of a positive selection process.

PMID- 9603467
TI  - IL-12-induced up-regulation of NKRP1A expression in human NK cells and consequent
      NKRP1A-mediated down-regulation of NK cell activation.
AB  - IL-12, in contrast to IL-2, strongly up-regulated the expression of the NKRP1A
      lectin molecule on human NK cells. This effect appeared to be specific for NKRP1A
      as the expression of other functional NK cell surface molecules such as CD16 and
      different killer inhibitory receptors (KIR) including CD158a and CD158b, p70 and
      p140 were not affected by culture in IL-12. In addition, we found that polyclonal
      or clonal NK cell populations derived in the presence of IL-2 displayed an
      increased expression of NKRP1A after culture in IL-12. The IL-12-induced NKRP1A
      expression was time and dose dependent, reaching a maximum by 7 days of culture
      in the presence of 2 ng/ml IL-12 and it was inhibited by the addition of anti-IL
      12 monoclonal antibody. The IL-12-dependent NKRP1A up-regulation was abrogated by
      the incubation of NK cells with actinomycin D, thus suggesting that IL-12 induces
      de novo transcription of NKRP1A mRNA. Functional analysis revealed that the
      engagement of the NKRP1A molecule in IL-12- but not in IL-2-cultured NK cells
      leads to a strong inhibition of the cytolytic activity induced by cross-linking
      of CD16 or p46, a recently described NK cell-specific triggering surface
      molecule. Our findings suggest that IL-12 up-regulates the expression of NKRP1A
      which, in turn, can regulate NK cell activation induced via different triggering
      pathways. This would imply that NKRP1A-mediated functions may be regulatd by the
      cytokine microenvironment that NK cells may encounter at inflammatory sites.

PMID- 9603468
TI  - Thymocyte activation induces the association of the proto-oncoprotein c-cbl and
      ras GTPase-activating protein with CD5.
AB  - Studies of knockout mice indicate that the glycoprotein CD5, which is expressed
      on Tcells, most thymocytes and a subset of B cells, down-regulates TCR- and B
      cell receptor (BCR)-mediated signaling. CD5 is associated with the TCR and BCR,
      and is phosphorylated on cytoplasmic tyrosine residues following antigen receptor
      ligation. Cross-linking of CD5 or pervanadate stimulation of thymocytes induces
      the association of a 120-kDa tyrosine-phosphorylated protein with CD5. The proto
      oncoprotein c-cbl associates with CD5 in pervanadate-stimulated thymocytes, and
      reprecipitation analysis demonstrates that the major proportion of CD5-associated
      pp120 is c-cbl. The GTPase-activating protein for ras (ras GAP), which is not
      tyrosine phosphorylated following CD5 cross-linking, associates with CD5 in
      pervanadate-stimulated thymocytes. Using tyrosine-phosphorylated peptides we show
      that ras GAP interacts in an SH2-mediated manner with the phosphorylated Y429SQP
      sequence of CD5. Both c-cbl and ras GAP have been proposed to suppress receptor
      mediated signaling, and may contribute to CD5-mediated suppression of TCR or BCR
      signaling.

PMID- 9603470
TI  - Transfer of antigen between dendritic cells in the stimulation of primary T cell
      proliferation.
AB  - Primary proliferative T cell responses require stimulation with antigen-pulsed
      dendritic cells (Ag-DC). Here we show that for optimal stimulation, dendritic
      cells (DC) not exposed directly to antigen are also required. Ag-DC added to DC
      depleted T cells caused negligible primary stimulation; adding back DC resulted
      in stimulation. These effects were seen using the contact sensitizer fluorescein
      isothiocyanate (FITC), FITC conjugated to ovalbumin (FITC-OVA) or influenza virus
      as antigens. DC co-cultured with Ag-DC (using FITC or FITC-OVA) acquired antigen
      indicating that antigen was transferred between DC. DC that acquired antigen
      secondarily were separated by cell sorting and stimulated primary T cell
      proliferation directly. DC were also pulsed with FITC, washed thoroughly and
      incubated overnight. Supernatants contained shed antigen since DC incubated in
      these supernatants acquired antigen as indicated by flow cytometry. DC acquiring
      the shed antigen also stimulated T cell proliferation although the stimulation
      was not as effective as that seen when cell contact between DC and antigen
      bearing DC occurred. Thus, in primary stimulation, activation of T cells may
      occur when there is an antigen gradient between Ag-DC and DC and the mechanisms
      underlying these effects are now being sought. We propose that this unique
      interaction between antigen-presenting cells may be a paradigm for self/non-self
      discrimination.

PMID- 9603469
TI  - Soluble antigen therapy induces apoptosis of autoreactive T cells preferentially
      in the target organ rather than in the peripheral lymphoid organs.
AB  - The administration of soluble myelin proteins is an effective way of down
      regulating the inflammation in the central nervous system (CNS) in experimental
      autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. To
      shed more light on the mechanism of this antigen-specific therapy, we determined
      the effect of the intraperitoneal (i.p.) injection of soluble myelin basic
      protein (MBP) on Tcell apoptosis in the CNS and peripheral lymphoid organs of
      Lewis rats with EAE induced by inoculation with MBP and complete Freund's
      adjuvant. In particular we assessed the level of apoptosis of Vbeta8.2+ Tcells,
      which constitute the predominant encephalitogenic MBP-reactive T cell population
      in the Lewis rat. The daily i.p. injection of MBP for 3 days from the onset of
      neurological signs inhibited the further development of neurological signs of
      EAE. Using two-color flow cytometry we found that a single i.p. injection of MBP
      increased the level of apoptosis of the Vbeta8.2+ T cell population in the CNS to
      26.2% compared to 7.4% in saline-treated rats and 7.6% in ovalbumin-treated rats.
      In contrast, treatment with MBP did not increase the level of apoptosis of the
      Vbeta8.2+ population in the popliteal lymph node draining the inoculation site
      (1.4%) or in the spleen (1.6%) above that occurring in saline-treated rats (1.6%
      and 1.1%, respectively). Limiting dilution analysis revealed that the frequency
      of T cells reactive to the major encephalitogenic epitope, MBP72-89, was
      decreased in the CNS but not in the popliteal lymph node by this treatment. Three
      color flow cytometry in MBP-treated rats demonstrated that CNS Vbeta8.2+ T cells
      expressing Fas (CD95) and Fas ligand were highly vulnerable to apoptosis compared
      to Vbeta8.2+ Tcells not expressing these proteins. We conclude that the i.p.
      injection of MBP increases the spontaneously occurring Fas-mediated activation
      induced apoptosis of autoreactive T cells in the CNS in EAE and that this
      contributes to the therapeutic effect of the injection.

PMID- 9603471
TI  - Inhibition of TCR/CD3-mediated signaling by a mutant of the hematopoietically
      expressed G16 GTP-binding protein.
AB  - We have investigated the role of the hematopoietically expressed G16 GTP-binding
      protein on T cell activation. We constructed transfectants of Jurkat T cells that
      express a function-deficient mutant of G alpha 16 predicted to prevent activation
      of this G protein. Upon stimulation with anti-CD3 epsilon antibodies, mutant G
      alpha 16 transfectants display a profound defect in the production of IL-2 and IL
      10, as well as in the expression of CD69. In contrast, the phorbol 12-myristate
      13-acetate (PMA)-induced IL-10 production and CD69 expression, and the ionomycin
      plus PMA-induced IL-2 production are not affected. Consistent with the reduction
      in cytokine production is the inhibition of early signaling events in the mutant
      G alpha 16-expressing cells. There are significant reductions in anti-epsilon
      induced tyrosine phosphorylation of zeta, epsilon, ZAP-70, and phospholipase C
      gamma 1, as well as in intracellular Ca2+ mobilization. In accordance with the
      effects on tyrosine phosphorylation is the reduction of TCR/CD3-mediated Fyn and
      Lck activities in G alpha 16 mutant cells. Even though the mechanism through
      which the G alpha 16 mutant mediates inhibition of T cell activation is not
      known, the data suggest a model where G proteins become activated upon TCR/CD3
      engagement and regulate the activation of tyrosine kinases and subsequent
      downstream signaling events that lead to the activation of cytokine genes.

PMID- 9603472
TI  - Down-regulation of surface antigens recognized by systemic lupus erythematosus
      antibodies on embryonal cells following differentiation and exposure to
      corticosteroids.
AB  - We have previously suggested that anti-DNA antibodies present in systemic lupus
      erythematosus patients can bind directly to tissues as a result of cross
      reactivity with embryonal tissue-based antigens. Here we have analyzed the
      interaction between polyclonal and monoclonal mouse and human lupus
      autoantibodies and an embryonal cell line. We report that a murine embryonal stem
      cell line (ES) expresses a surface antigen which is recognized by mouse and human
      lupus autoantibodies. This surface antigen is down-regulated following maturation
      of the cells or incubation with corticosteroids. Adhesion molecules may serve as
      the target membrane antigen in ES cells since preincubation with these antibodies
      decreases the ability of ES cells to adhere to the plate.

PMID- 9603473
TI  - Expression in cytotoxic T lymphocytes of a single-chain anti-carcinoembryonic
      antigen antibody. Redirected Fas ligand-mediated lysis of colon carcinoma.
AB  - In the MD45 mouse cytotoxic T lymphocyte (CTL) hybridoma cell line, we have
      expressed a chimeric receptor, consisting of the single-chain variable domains
      (scFv) of anti-carcinoma embryonic antigen (CEA) mAb linked to Fcgamma receptor
      (FcgammaR) chain via a CD8 hinge. Transfected MD45 subclones lysed CEA-positive
      human colon carcinoma cell lines in an antigen-specific and FasL-dependent
      manner. The degree of lysis correlated with the level of chimeric receptor
      expressed on transduced MD45 subclones. The requirement for an intact Y65TGL
      motif in the signaling gamma chain suggested that interaction of the chimeric
      receptor with target cell CEA induced the cytotoxicity of MD45-scFv subclones.
      However, MD45 expressing a Y65F mutant chimera still displayed minor levels of
      lysis following PMA stimulation, suggesting that PMA could bypass gamma chain
      induction of functional FasL. Pretreatment of Fas-resistant CEA-positive colon
      carcinoma target cells with IFN-gamma increased their sensitivity of MD45-scFv
      subclones and FasL-mediated lysis. This study has demonstrated the successful
      activation of FasL function via a chimeric receptor introduced into lymphocytes
      and the susceptibility of human colon carcinoma to combined cytokine and CTL
      treatment.

PMID- 9603474
TI  - Influence of extracellular matrix proteins on the development of cultured human
      dendritic cells.
AB  - The development of dendritic cells (DC) is still only partly understood. Recently
      established culture systems using CD34+ cells or monocytes as precursor cells for
      the generation of DC indicate the necessity of pro-inflammatory cytokines for
      their development. In vivo the contact to other cells or to the proteins of the
      extracellular matrix might also be essential for their development. In our
      experiments we used granulocyte-macrophage colony-stimulating factor- and IL-4
      treated human monocytes as precursor cells to investigate the interaction of DC
      at different maturation stages with the matrix proteins fibronectin, collagen
      type I and collagen type IV. We demonstrate a strong beta1-integrin-mediated
      adherence of immature DC to fibronectin that is lost completely during
      maturation. The binding to collagen type I was less strong but induced a
      maturation of the precursor cells. After 3 days of culture on this protein, the
      cells showed all features of fully matured DC such as expression of CD83 and an
      excellent allostimulatory capacity. The reason for this effect was shown to be
      the induction of TNF-alpha production by the DC themselves. In contrast to the
      adhesion to fibronectin, the maturation and the cytokine production of DC induced
      by collagen type I could not be inhibited by blocking of beta1-integrins. These
      results indicate that proteins of the extracellular matrix play an important role
      in the development and function of human DC.

PMID- 9603475
TI  - Role of natural killer cells and TCR gamma delta T cells in acute autoimmune
      encephalomyelitis.
AB  - To elucidate the role of NK cells and TCR gamma delta+ T cells in acute
      experimental autoimmune encephalomyelitis (EAE) induced in Lewis rats, the
      distribution, number and function of these cells were studied using several
      methods. Immunohistochemical and flow cytometric analysis revealed that a certain
      number of NK cells (17 of the total inflammatory cells) infiltrated the central
      nervous system (CNS) at the peak stage of EAE and were mainly located in the
      perivascular region. On the other hand, virtually no TCR gamma delta+ T cells
      were found in the CNS. NK-T (NKR-P1+TCR alpha beta+) cells were few and did not
      increase in number in the CNS and lymphoid organs. In the cytotoxic assay using
      YAC-1 cells, effector cells isolated from the spleen of rats at the peak of EAE
      showed essentially the same cytotoxicity as those isolated from normal controls
      although the total number of NK cells decreased to one fifth of that of normal
      rats. Furthermore, in vivo administration of anti-NK cell (3.2.3 and anti-asialo
      GM1), but not of anti-TCR gamma delta (V65), antibodies exacerbated the clinical
      features of EAE and induced fatal EAE in some rats. These findings suggest that
      NK cells play a suppressive role in acute EAE whereas TCR gamma delta+ T cells
      are not involved in the development of or recovery from the disease.

PMID- 9603476
TI  - ChemR23, a putative chemoattractant receptor, is expressed in monocyte-derived
      dendritic cells and macrophages and is a coreceptor for SIV and some primary HIV
      1 strains.
AB  - Leukocyte chemoattractants act through a rapidly growing subfamily of G protein
      coupled receptors. We report the cloning of a novel human gene encoding an orphan
      receptor (ChemR23) related to the C3a, C5a and formyl Met-Leu-Phe receptors, and
      more distantly to the subfamilies of chemokine receptors. ChemR23 transcripts
      were found to be abundant in monocyte-derived dendritic cells and macrophages,
      treated or not with LPS. Low expression could also be detected by reverse
      transcription-PCR in CD4+ T lymphocytes. The gene encoding ChemR23 was assigned
      by radiation hybrid mapping to the q21.2-21.3 region of human chromosome 12,
      outside the gene clusters identified so far for chemoattractant receptors. Given
      the increasing number of chemoattractant receptors used by HIV-1, HIV-2 and SIV
      as coreceptors, ChemR23 was tested in fusion assays for potential coreceptor
      activity by a range of viral strains. None of the tested HIV-2 strains made use
      of ChemR23 as a coreceptor, but several SIV strains (SIVmac316, SIVmac239,
      SIVmacl7E-Fr and SIVsm62A), as well as a primary HIV-1 strain (92UG024-2) used it
      efficiently. ChemR23 therefore appears as a coreceptor for immunodeficiency
      viruses that does not belong to the chemokine receptor family. It is also a
      putative chemoattractant receptor relatively specific for antigen-presenting
      cells, and it could play an important role in the recruitment or trafficking of
      these cell populations. Future work will be required to identify the ligand(s) of
      this new G protein-coupled receptor and to define its precise role in the
      physiology of dendritic cells and macrophages.

PMID- 9603477
TI  - Characterization of the CD55 (DAF)-binding site on the seven-span transmembrane
      receptor CD97.
AB  - CD97 is an activation-induced antigen on leukocytes which belongs to a new group
      of seven-span transmembrane (7-TM) molecules, designated EGF-TM7 family. Family
      members, including EMR1 and F4/80, are characterized by an extended extracellular
      region with several N-terminal epidermal growth factor-like (EGF) domains.
      Alternative splicing of CD97 results in isoforms possessing either three (EGF1,
      2, 5), four (EGF1, 2, 3, 5) or five EGF domains (EGF1, 2, 3, 4, 5). We recently
      identified decay accelerating factor (DAF, CD55), a regulatory protein of the
      complement cascade, as a cellular ligand of the smallest isoform. Employing
      mutants of CD97(EGF1, 2, 5) in which the EGF domains have been systematically
      deleted, we here demonstrate the necessity of at least three tandemly linked EGF
      domains for the interaction with CD55. Consistent with the involvement of
      different EGF domains, monoclonal antibodies directed against the first EGF
      domain as well as the removal of Ca2+, for which binding sites exist in the
      second and fifth EGF domain, blocked binding to CD55. Compared to CD97(EGF1, 2
      ,5) the larger isoforms CD97(EGF1, 2, 3, 5) and CD97(EGF1, 2, 3, 4, 5) have a
      significantly lower affinity for CD55. Thus, alternative splicing may regulate
      the ligand specificity of CD97 and probably other members of the EGF-TM7 family.

PMID- 9603478
TI  - VCAM-1 is internalized by a clathrin-related pathway in human endothelial cells
      but its alpha 4 beta 1 integrin counter-receptor remains associated with the
      plasma membrane in human T lymphocytes.
AB  - Lymphocyte extravasation involves a step(s) of de-adhesion to allow trans- and
      subendothelial migration in response to inflammatory signals. We show here that
      ligated VCAM-1 was rapidly internalized (t1/2 14.5 min) in ECV 304 endothelial
      cells and in TNF-alpha-primed human umbilical vein-derived endothelial cells
      (t1/2 11.2 min). The process required energy (ATP), intracellular Ca2+, an intact
      cytoskeletal network and active protein kinases. The internalization of VCAM-1
      involved a clathrin-dependent pathway based on the observations that 1) it was
      inhibited in cells treated with lysosomotropic agents or with a hypertonic
      concentration of sucrose, and 2) internalized VCAM-1 colocalized with clathrin.
      In contrast, the cross-linked alpha 4 beta 1 integrin counter-receptor of VCAM-1
      remained associated with the plasma membrane of purified peripheral T and Jurkat
      cells. Our results suggest a model where VCAM-1 would initially participate in
      the retention of T cells to the endothelium by binding alpha 4 beta 1 integrin.
      Lymphocyte de-adhesion would be facilitated as a result of the internalization of
      VCAM-1. The persistent cell surface expression of alpha 4 beta 1 integrin would
      allow the migrating T cells to interact with and receive signal(s) from its
      fibronectin ligand of the extracellular matrix.

PMID- 9603479
TI  - IL-10-mediated suppression of TNF-alpha production is independent of its ability
      to inhibit NF kappa B activity.
AB  - IL-10 has a well-characterized anti-inflammatory role that includes the
      suppression of inflammatory cytokine (e.g. TNF-alpha) production by
      monocytic/macrophage cells. Both transcriptional and post
      transcriptional/translational mechanisms have been proposed to explain this
      process. In this study we observed that IL-10 inhibited nuclear NF kappa B DNA
      binding activity without affecting I kappa B degradation or translocation of NF
      kappa B subunits to the nucleus. While the suppression of NF kappa B in 70Z/3 pre
      B cells correlated with suppression of NF kappa B transcriptional activity and
      expression of surface IgM, it did not correlate with the production of TNF-alpha
      mRNA or protein in RAW 264.7 macrophages. Similar observations in the macrophages
      were made with a second anti-inflammatory cytokine, IL-4. Therefore we conclude
      that although IL-10 or IL-4 can suppress NF kappa B activity, this appears to
      have little effect on the expression of the TNF-alpha gene and is unlikely to be
      the basis of the anti-inflammatory effects of these cytokines.

PMID- 9603480
TI  - Interleukin-6 functions in autoimmune encephalomyelitis: a study in gene-targeted
      mice.
AB  - The encephalitogenic peptide pMOG 35-55 from the myelin oligodendrocyte
      glycoprotein was used to induce experimental autoimmune encephalomyelitis (EAE)
      in H-2b mice with the interleukin-6 (IL-6) gene intact or disrupted. The IL-6+/+
      mice developed a chronic form of EAE ascending paralysis, whereas the IL-6-/-
      mice were resistant to the disease. Injections of recombinant IL-6 following pMOG
      immunization induced severe disease in the IL-6-/- mice. Histological examination
      of brain and spinal cord sections showed that the perivascular infiltration of
      inflammatory cells evident in IL-6+/+ mice was absent in the IL-6-/- animals and
      could be restored by exogenous IL-6 administration. Anti-MOG antibody levels were
      much lower in the IL-6-/- mice, but were not restored to high levels by IL-6
      injections which elicited the development of pMOG 35-55-induced EAE. T
      lymphocytes reactive to the pMOG antigen were recovered from lymph nodes of both
      types of mice and Tcell lines could be established from both. Adoptive transfer
      of Tcell lines from IL-6+/+ mice induced EAE in the mice with the intact IL-6
      gene but less in the IL-6-deficient mice, indicating that the resistant phenotype
      cannot be explained solely by lack of encephalitogenic Tcells. The absence of
      cell infiltrates in the brain and spinal cords of IL-6-/- mice upon adoptive
      transfer of the pathogenic Tcells from IL-6+/+ mice is consistent with a function
      of IL-6 in the local perivascular inflammatory process.

PMID- 9603481
TI  - Demonstration of identical expanded clones within both CD8+CD28+ and CD8+CD28- T
      cell subsets in HIV type 1-infected individuals.
AB  - In HIV-1-infected individuals, the CD8+CD28- T cell subset is considerably
      expanded and is frequently the largest subset of T cells found in peripheral
      blood. It has been assumed, but not proven, that CD8+CD28- T cells derive from
      CD8+CD28+ T cells in vivo. To further study the ontogeny of CD8+CD28- T cells, we
      have performed analyses of the complementarity determining region 3 (CDR3) of the
      TCRB of CD8+CD28+ and CD8+CD28- T cells from the peripheral blood of HIV-1
      infected individuals. When cells from the same individual were compared, expanded
      peaks in CDR3 length analysis within a given BV family were frequently observed
      at the same location in both CD8+ subsets (p < 0.001). Sequencing of cDNA
      corresponding to dominant peaks revealed the presence of identical expanded CD8+
      T cell clones within both the CD28+ and CD28- subsets on eight of nine attempts.
      Our results show that CD8+CD28+ and CD8+CD28- T cells are phenotypic variants of
      the same lineage, most likely evolving from CD8+CD28+ to end-stage CD8+CD28- T
      cells.

PMID- 9603482
TI  - Plasmodium falciparum: detection of polymorphisms in the dihydrofolate reductase
      and dihydropteroate synthetase genes by PCR and restriction digestion.
AB  - With the spread of resistance to chloroquine, the combination of sulphadoxine and
      pyrimethamine is growing in importance for the treatment of infection with the
      malaria parasite Plasmodium falciparum. Mutations in the dhfr gene of P.
      falciparum have been associated with resistance to pyrimethamine. Recently,
      several polymorphisms have been identified in the P. falciparum dhps gene which
      may correlate with sulphadoxine-resistance. Simple and rapid tests have been
      developed to detect these polymorphisms, using PCR followed by restriction
      digestion. These tests can accurately identify all the polymorphisms described to
      date at codons 16, 51, 59, 108, and 164 in the dhfr gene and those at codons 436,
      437, 540, 581, and 613 in the dhps gene. A nested system has been developed which
      allows the accurate detection of these polymorphisms in samples of fingerprick
      blood collected on glass fiber membranes and filter papers, some with very low
      parasitaemias.

PMID- 9603483
TI  - Hypoxanthine, guanine, xanthine phosphoribosyltransferase activity in
      Cryptosporidium parvum.
AB  - All parasitic protozoa examined to date are incapable of de novo synthesis of
      purine nucleotides and rely on salvage mechanisms for survival. We have
      identified hypoxanthine, guanine, xanthine phosphoribosyl-transferase activities
      in crude cell-free extracts of Cryptosporidium sporulated oocysts utilizing
      radiolabeled substrates. Guanine, hypoxanthine, and xanthine were converted to
      their corresponding mononucleotides with specific activities of 346, 280, and 108
      nmol/min/mg protein, respectively. The conversion of the radiolabeled purines was
      examined in the presence of another, unlabeled, purine base. These competition
      assays showed that both hypoxanthine and guanine were capable of inhibiting
      conversion of hypoxanthine, guanine, and xanthine to the corresponding
      nucleotides. Xanthine had a much lower inhibitory effect on the conversion of
      guanine and hypoxanthine to the nucleotides, whereas adenine had no effect at
      all. Autoradiographic studies of Cryptosporidium-infected Madin-Darby canine
      kidney (MDCK) cells showed that radiolabeled hypoxanthine, guanine, and adenine
      were primarily incorporated by intracellular Cryptosporidium as well as by MDCK
      nuclei. No apparent incorporation of xanthine by either host cells or
      intracellular parasites occurred. Radiolabeled glycine and formate were
      incorporated only into the nuclei of MDCK cells, suggesting a lack of de novo
      synthesis of purine nucleotides in Cryptosporidium. Radiolabeled hypoxanthine and
      guanine were also incorporated by excysting Cryptosporidium sporozoites.
      Altogether, our results indicate the presence of HPRTase, GPRTase, and XPRTase
      activities. These activities may play an important role in purine salvage, and
      may localize to a single HGXPRTase enzyme, as in the case of Eimeria, Toxoplasma,
      and Plasmodium.

PMID- 9603484
TI  - Strongyloides venezuelensis: binding of orally secreted adhesion substances to
      sulfated carbohydrates.
AB  - Adhesion substances produced by adult worms of Strongyloides venezuelensis bound
      strongly to hepin-Sepharose beads after incubation at 37 degrees C for 1 h. This
      binding was completely inhibited by highly sulfated carbohydrates such as soluble
      heparin, dextran surfate, fucoidan, and pentosan polysulfate. Chondroitin sulfate
      E and chondroitin sulfate A inhibited to a lesser degree and chondroitin sulfate
      C and dextran did not inhibit significantly. Carbohydrate moieties as well as the
      number and position of negatively charged sulfate groups of sulfated glycans were
      important determinants for the interaction between sulfated carbohydrates and
      adhesion substances. Adhesion substances of S. venezuelensis adult worms also
      bound to negatively charged rat red blood cells. The binding was significantly
      inhibited by heparin but not by mono- or disaccharides. Thus the intraction
      between red cells and adhesion substances was electrostatic in nature, but did
      not involve lectin-sugar interactions.

PMID- 9603485
TI  - Trypanosoma brucei: comparison of circulating strains in an endemic and an
      epidemic area of a sleeping sickness focus.
AB  - Human sleeping sickness in East Africa is characterized by periods of long-term
      endemicity interspersed with short-term epidemics. The factors generating these
      huge changes are largely uncharacterized but probably reflect complex
      interactions among socioeconomic factors, ecological factors, and the movement
      and diversity of trypanosome strains. To investigate the role of trypanosome
      strains in the generation of these epidemics, we addressed two important
      questions. (1) Are the trypanosome strains circulating within a focus the same
      during times of endemicity and during an epidemic? (2) How stable are trypanosome
      strains within a single animal reservoir host? Using restriction fragment length
      polymorphism analysis of repetitive DNA, we have examined the relationship
      between Trypanosoma brucei isolates, taken from the Busoga focus of human
      sleeping sickness, during an endemic period (Busia, Kenya, 1993-1994) and stocks
      isolated during an epidemic period (Tororo, Uganda, 1988-1990). We show that
      similar strains, including human infective strains, are circulating in domestic
      cattle (the most significant animal reservoir) in both epidemic and endemic areas
      of the Busoga focus. Furthermore, we show the important finding that individual
      animals harbor the same genotype of T. brucei for a period of time and may be
      clonal for a given parasite strain.

PMID- 9603486
TI  - Trypanosoma cruzi: impact of clonal evolution of the parasite on its biological
      and medical properties.
AB  - Trypanosoma cruzi populations are subdivided into natural clones that can exhibit
      considerable genetic differences. It has been proposed that T. cruzi clonal
      structure has a major impact on this parasite's biological properties. The
      present work aims at testing this hypothesis. Twenty-one stocks isolated from
      various ecological cycles, places, and hosts were characterized by multilocus
      enzyme electrophoresis (MLEE) with 22 genetic loci and random amplification of
      polymorphic DNA (RAPD) with 10 primers on the one hand and by 14 different
      biological parameters on the other hand. These parameters were related to: (i)
      growth kinetics of epimastigotes and amastigotes; (ii) infection of culture cells
      by amastigotes; (iii) viability of extracellular trypomastigotes; or (iv)
      sensitivity of epimastigotes, trypomastigotes, and amastigotes to Benznidazole
      and Nifurtimox. MLEE and RAPD results exhibited parity to each other, as
      previously noted (M. Tibayrenc, K. Neubauer, C. Barnabe, F. Guerrini, D.
      Skarecky, and F. J. Ayala, 1993, Proceedings of the National Academy of Sciences
      of the USA 90, 1335-1339), and showed that the 21 stocks were distributed into
      three main genetic groups, 19/20, 32, and 39, corresponding to the major clones
      19, 20, 32, and 39 previously described on the basis of 15 isozyme loci. Most
      biological parameters showed a strong correlation to the genetic distances
      evaluated from either MLEE or RAPD, which favors the working hypothesis. The only
      exception came from drug sensitivity estimated on trypomastigote forms. The
      overall results made it possible to firmly reject the null hypothesis that there
      is no relationships between evolutionary distances and biological differences in
      T. cruzi natural clones.

PMID- 9603487
TI  - Plasmodium falciparum: influence of malarial and host erythrocyte skeletal
      protein interactions on phosphorylation in infected erythrocytes.
AB  - Phosphorylation of components of the erythrocyte membrane skeleton has major
      effects on the physical properties of the membrane. Infection of red cells by the
      protozoan parasite Plasmodium falciparum leads to a marked increase in the level
      of phosphorylation of red cell protein 4.1 and the insertion into the red cell
      skeleton of parasite-encoded phosphoproteins, including the mature-parasite
      infected erythrocyte surface antigen (MESA). Because of the tight association of
      MESA with protein 4.1, we set out to determine the importance of this interaction
      and that of other parasite-encoded skeletal-associated proteins to
      phosphorylation of the infected red cell membrane. Our results show that neither
      MESA nor protein 4.1 is required for phosphorylation of its binding partner.
      Further, phosphorylation of MESA and protein 4.1 occurs independently of the
      presence of knobs, the expression of PfHRP1, or cytoadherence phenotype. In
      contrast to previous studies, we were unable to detect a change in the molecular
      weight of protein 4.1 in erythrocytes infected with cytoadherent parasite lines.
      In red cells infected with parasites expressing PfHRP1 (K+), MESA and protein 4.1
      are substrates for a kinase with the inhibitor profile of a casein kinase.
      Surprisingly, however, when we examined phosphorylation of MESA and protein 4.1
      in K(-)-infected erythrocytes, we found that casein kinase I and II inhibitors
      had no, or greatly reduced, effectiveness, and in fact, phosphorylation of these
      two proteins was enhanced in some instances.

PMID- 9603489
TI  - Leishmania amazonensis: long-term cultivation of axenic amastigotes is associated
      to metacyclogenesis of promastigotes.
AB  - Axenic Leishmania amazonensis cultures were obtained (with 2 years of follow-up)
      in Schneider's medium at pH 5.5 and a temperature of 32 degrees C.
      Differentiation of promastigotes into amastigotes is directly associated with the
      metacyclogenesis rate of the original promastigotes. Promastigote cultures
      containing different percentages of metacyclic forms, as evaluated by the
      complement lysis test, resulted in axenic amastigote cultures containing a
      variable amount of undifferentiated forms. We observed that a culture originally
      containing a large amount of metacyclic forms (73%) underwent a complete
      differentiation process, resulting in a 100% amastigote culture with no
      promastigote forms. All other cultures (with a decreasing amount of metacyclic
      forms: 50% and fewer) failed to differentiate completely, resulting in cultures
      with increasing percentages of promastigote contamination. The
      amastigote/promastigote rate in these cultures has been maintained at the same
      level thus far. The axenic Leishmania amazonensis amastigotes were cryopreserved,
      thawed as such, and successfully cultivated under appropriately defined growth
      conditions.

PMID- 9603488
TI  - Plasmodium yoelii: differences in the transcription of the 235-kDa rhoptry
      protein multigene family in lethal and nonlethal lines.
AB  - We have compared the transcription of the 235-kDa rhoptry protein (p235)
      multigene family in the lethal (YM) and nonlethal (17X) lines of the rodent
      malaria parasite Plasmodium yoelii. This protein is thought to be involved in
      erythrocyte invasion by the parasite. Using a PCR-based approach we demonstrated
      that both lines have similar p235 families. However, RT-PCR analysis revealed
      that this similarity is not evident at the level of transcription, with the
      lethal line not transcribing a whole subset of its p235 gene repetoire. Specific
      anti-p235 immune pressure induces differences in invasion properties of the
      lethal line; we were, however, unable to detect any changes in the transcription
      pattern of the p235 genes associated with this event.

PMID- 9603491
TI  - Entamoeba histolytica HM1:IMSS: hemoglobin-degrading neutral cysteine proteases.
AB  - Entamoeba histolytica HMI:IMSS trophozoites were able to utilize human hemoglobin
      but not hemin as a sole iron source to grow in vitro. Proteases from crude
      extracts of E. histolytica degraded human, porcine, and bovine hemoglobins at pH
      7.0. These proteolytic activities were found by electrophoresis in SDS
      polyacrylamide gels copolymerized with hemoglobin, with apparent molecular
      weights of 116, 82, and 21 kDa, the 82-kDa protein being the most active protease
      against this substrate. The proteases were classified in the cysteine group since
      the activities were inhibited by l-trans-epoxysuccinylleucylamido(4
      guanidino)butane, p-hydroxymercuribenzoate, iodoacetate, and N-ethylmaleimide and
      activated with dithiothreitol. Other pathogenic strains of E. histolytica showed
      the same pattern of hemoglobinases. These hemoglobin-degrading proteases could be
      playing an important role in iron acquisition by E. histolytica.

PMID- 9603490
TI  - Trypanosoma brucei: molecular cloning and stage-regulated expression of a malate
      dehydrogenase localized to the mitochondrion.
AB  - African trypanosomes exhibit dramatic developmental changes in carbohydrate and
      energy metabolism, with cytochrome-mediated respiration playing an important role
      only in the insect stages. The parasites possess three isozymes of malate
      dehydrogenase, each of which has a different subcellular localization and,
      likely, a distinct metabolic role. We have cloned and characterized a cDNA
      encoding one of these malate dehydrogenases. Epitope tagging and transfection
      experiments demonstrate that the corresponding protein is localized to the
      mitochondrion and that an intact amino terminus is required for proper
      compartmentalization. The abundance of transcript is developmentally regulated,
      with higher levels in procyclic stage parasites.

PMID- 9603492
TI  - Plasmodium falciparum: thrombospondin mediates parasitized erythrocyte band 3
      related adhesin binding.
AB  - Plasmodium falciparum-parasitized red cells attach to endothelial cells through
      several receptor-adhesin pairs. One of the adhesins on the surface of malaria
      infected red blood cell is the modified band 3 molecule. We tested a synthetic
      peptide (HPLQKTY) based on a peptidic sequence of human band 3 protein to
      determine whether CD36 or thrombospondin is a receptor for the band 3-related
      adhesin. Although both CD36 and thrombospondin can bind parasitized cells
      independently, the HPLQKTY peptide and a monoclonal antibody (3H3) that
      recognizes the HPLQKTY sequence blocked only the adhesion of parasitized red
      cells to thrombospondin. The binding of thrombospondin, but not CD36, to the
      immobilized multiple antigen peptide-conjugated HPLQKTY was dependent on the
      concentration of the immobilized peptide. It would appear therefore, that
      thrombospondin is a receptor for the band 3-related cytoadhesion of parasitized
      erythrocytes.

PMID- 9603493
TI  - Prolonged oviposition decreases the ability of the parasitoid Leptopilina
      boulardi to suppress the cellular immune response of its host Drosophila
      melanogaster.
AB  - The cellular immune response of Drosophila against metazoan parasites is
      characterized by the production of melanotic capsules comprised mostly of host
      blood cells (hemocytes). During the latter part of the ovipositional period of
      the cynipid wasp parasitoid Leptopilina boulardi, eggs are deposited into host
      larvae of Drosophila melanogaster that are more susceptible to destruction by
      melanotic encapsulation than are eggs laid earlier. The increase in parasitoid
      mortality is attributed to a decline in the wasp's ability to suppress the host
      immune response. The decrease in active immune suppression is dependent on the
      reproductive physiology of the wasp, and this correlates with the extent of her
      prior ovipositional experience and not on her chronological age nor on the number
      of eggs remaining in the ovarioles. Such females with prior ovipositional
      experience which lack the ability to immune suppress infect far fewer hosts than
      females with no prior ovipositional experience. The reluctance of experienced
      wasps to infect hosts is not due to egg depletion, but instead is attributed to a
      depletion in immune suppressive substances. Perhaps by ovipositional restraints,
      retaining eggs that would otherwise become encapsulated reduces selection
      pressure in host populations for specific immune reactivity.

PMID- 9603495
TI  - Plasmodium gallinaceum: differential killing of some mosquito stages of the
      parasite by insect defensin.
AB  - We examined several insect antimicrobial peptides to study their effect on
      Plasmodium gallinaceum zygotes, ookinetes, oocysts, and sporozoites. Only two
      insect defensins-Aeschna cyanea (dragon fly) and Phormia terranovae (flesh fly)
      had a profound toxic effect on the oocysts in Aedes aegypti and on isolated
      sporozoites. The defensins affected the oocysts in a time-dependent manner.
      Injecting the peptide into the hemolymph 1 or 2 days after an infectious blood
      meal had no significant effect on prevalence of infection or relative oocyst
      density per mosquito. When injected 3 days after parasite ingestion, the relative
      oocyst density was significantly reduced. Injection on day 4 or later damaged the
      developing oocysts, although the oocysts density per mosquito was not
      significantly different when examined on day 8. The oocysts were swollen or had
      extensive internal vacuolization. The peptides had no detectable effect on the
      early stages of the parasite: the zygotes and ookinetes tested in vitro. Both the
      defensins were highly toxic to isolated sporozoites in vitro as indicated by
      disruption of the membrane permeability barrier, a change in morphology, and loss
      of motility. In contrast to the toxicity of cecropin and magainin for mosquitoes,
      defensin, at concentrations that kill parasites, is not toxic to mosquitoes,
      suggesting that defensin should be studied further as a potential molecule to
      block sporogonic development of Plasmodium.

PMID- 9603494
TI  - Hymenolepsis diminuta: mucosal mastocytosis and intestinal smooth muscle
      hypertrophy occur in tapeworm-infected rats.
AB  - The mechanisms mediating motility changes during noninvasive tapeworm infection
      have not been characterized. In contrast, host intestinal motility changes during
      invasive nematode infection are mediated by mucosal mast cells (MMC). The purpose
      of this study was to examine and the correlate onset of myoelectric alterations 8
      days after initial tapeworm infection with changes in intestinal morphology, MMC
      numbers, and MMC secretory activity. Segments of the small intestine, the
      tapeworms normal habitat, along with stomach, colon, and bladder were taken from
      tapeworm-infected and control rats. Tissues were fixed and stained to identify
      MMC and for morphologic measurement. Tapeworm-infected and uninfected rats with
      chronically implanted intestinal electrodes were treated with ketotifen, a mast
      cell stabilizer, and in vivo myoelectric activity monitored. In tapeworm-infected
      rats, the muscularis externa, on day 20 postinfection, and crypts of Lieberkuhn,
      on day 26 postinfection, from the entire small intestine appeared thickened or
      deeper, respectively. Increased muscularis thickness was due to smooth muscle
      hypertrophy in both the circular and the longitudinal muscle layers. Mucosal
      mastocytosis was first observed on day 26 postinfection and occurred only in the
      ileum of tapeworm-infected rats. Pharmacologic stabilization of mast cells with
      ketotifen did not prevent onset of enteric myoelectric alterations during
      tapeworm infection. Stomach, colon, and bladder MMC numbers and tissue dimensions
      were not different between Hymenolepis diminuta-infected rats and uninfected
      controls. Initiation of myoelectric alterations 8 days after infection precedes
      and may be a contributing factor to the onset of both smooth muscle hypertrophy
      and mucosal mastocytosis. Taken together, our data indicate that mast cells are
      not an initiating factor nor chronic stimulus maintaining intestinal myoelectric
      alterations during H. diminuta infection.

PMID- 9603496
TI  - Encephalitozoon intestinalis: humoral responses in interferon-gamma receptor
      knockout mice infected with a microsporidium pathogenic in AIDS patients.
AB  - IFN-gamma receptor knockout mice and wild-type mice were infected per os with
      Encephalitozoon intestinalis. Both groups developed an infection that was chronic
      in the mutant mice whereas it was only transient in wild-type mice. The infection
      of mutant mice was characterized by the continual shedding of spores in feces,
      splenomegaly, the enlargement of the biliary tract, and the occurrence of
      numerous nodules in the liver and in the small intestine wall. The humoral
      response was studied by ELISA, IFA, and Western blotting. ELISA titers of anti-E.
      intestinalis antibodies of IgG, IgM, and IgA isotypes were higher in IFN-gamma
      R0/0 mice than in wild-type mice and they increased in time after infection.
      Levels of IgG2a were inferior to those of IgG1 in mutant mice in contrast to wild
      type mice. High levels of parasite specific antibodies were accompanied by an
      increase in type 2 cytokines (IL-4 and IL-10) secretion in the duodenum of IFN
      gamma R0/0 mice. The E. intestinalis spore wall was recognized by IgM, IgG, and
      IgA from all infected mice whereas the extruded polar tube only reacted with IgG
      and IgA from IFN-gamma R0/0 mice after 45 days of the infection. IFN-gamma R0/0
      mice IgG and IgA reacting with polar tube identified also a series of proteins
      which could be components of this structure. On the proteins recognized by all
      infected mice sera, two were first recognized by IgM at day 15 and then by IgG at
      day 30 in wild-type (WT) mice. The persistent reactivity of all proteins in
      mutant mice is consistent with the chronicity of the infection in these animals;
      in contrast, their resorption at day 30 in WT animals corroborates the transient
      character of the infection in these mice. The correlation between the evolution
      of the proteic pattern and the development of the infection provides evidence of
      the validity of this murine model to study human microsporidiosis. Indeed the
      reported results confirm the potential value of serological methods for
      diagnosing E. intestinalis infection in immunocompetent and in immunocompromised
      human subjects, for elucidating the age pattern of the microsporidiosis and also
      for identifying risk groups.

PMID- 9603497
TI  - Chromatin organization during the nuclear division stages of live Entamoeba
      histolytica trophozoites.

PMID- 9603498
TI  - Plasmodium falciparum: ribosomal P2 protein gene expression is independent of the
      developmentally regulated rRNAs.

PMID- 9603499
TI  - Plasmodium falciparum: the importance of IgM in the rosetting of parasite
      infected erythrocytes.

PMID- 9603500
TI  - Salivary gland lysate from the sand fly Lutzomyia longipalpis suppresses the
      immune response of mice to sheep red blood cells in vivo and concanavalin A in
      vitro.

PMID- 9603501
TI  - Toxoplasma gondii: a paraformaldehyde-insensitive diaphorase activity acts as a
      specific histochemical marker for the single mitochondrion.

PMID- 9603502
TI  - A hypothesis for the tissue specificity of nematode parasites.
AB  - Recent work from Riddle and coworkers has shown that in the free-living soil
      nematode, Caenorhabditis elegans, the decision to become a developmentally
      arrested, dispersal form known as the dauer ("enduring") larva is controlled, at
      least in part, by transcription of a wild-type allele at the daf-7 locus. daf-7
      mutants are "constitutive dauers." Using this model as a general paradigm for
      nematode development, I propose that many nematode parasites behave as though
      they were daf-7 mutants. This will ensure developmental arrest at the L3 stage. I
      further propose that these organisms obtain the daf-7 gene product required for
      reentry into the developmental pathway from the mammalian host and that their
      tissue localization is dictated by the daf-7 homologue that is uniquely
      recognized by the cognate receptor.

PMID- 9603503
TI  - Problems with media gatekeepers.

PMID- 9603504
TI  - UN agency chief seeks advice from environment groups.

PMID- 9603505
TI  - Company aims to beat NIH human genome efforts.

PMID- 9603506
TI  - Australia's research budget to remain flat for three years.

PMID- 9603507
TI  - German chemicals giant to focus on life sciences.

PMID- 9603508
TI  - Cancer 'cure' article stirs up hot debate.

PMID- 9603510
TI  - Italian defeatism unwarranted.

PMID- 9603511
TI  - Out of order.

PMID- 9603513
TI  - Transcription sans TBP.

PMID- 9603512
TI  - The fraud of Abderhalden's enzymes.

PMID- 9603514
TI  - Cocaine and the serotonin saga.

PMID- 9603515
TI  - Imprinted gene in postnatal growth role.

PMID- 9603516
TI  - Life-support system benefits from noise.

PMID- 9603517
TI  - Sphenoid shortening and the evolution of modern human cranial shape.
AB  - Crania of 'anatomically modern' Homo sapiens from the Holocene and Upper
      Pleistocene epochs differ from those of other Homo taxa, including Neanderthals,
      by only a few features. These include a globular braincase, a vertical forehead,
      a dimunitive browridge, a canine fossa and a pronounced chin. Humans are also
      unique among mammals in lacking facial projection: the face of the adult H.
      sapiens lies almost entirely beneath the anterior cranial fossa, whereas the face
      in all other adult mammals, including Neanderthals, projects to some extent in
      front of the braincase. Here I use radiographs and computed tomography to show
      that many of these unique human features stem partly from a single,
      ontogenetically early reduction in the length of the sphenoid, the central bone
      of the cranial base from which the face grows forward. Sphenoid reduction,
      through its effects on facial projection and cranial shape, may account for the
      apparently rapid evolution of modern human cranial form, and suggests that
      Neanderthals and other archaic Homo should be excluded from H. sapiens.

PMID- 9603518
TI  - Regulation of leaf initiation by the terminal ear 1 gene of maize.
AB  - Higher plants elaborate much of their architecture post-embryonically through
      development initiated at the tips of shoots. During vegetative growth, leaf
      primordia arise at predictable sites to give characteristic leaf arrangements, or
      phyllotaxies. How these sites are determined is a long-standing question that
      bears on the nature of pattern-formation mechanisms in plants. Fate-mapping
      studies in several species indicate that each leaf primordium becomes organized
      from a group of 100-200 cells on the flank of the shoot apex. Although molecular
      studies indicate that the regulated expression of specific homeobox genes plays
      some part in this determination process, mechanisms that regulate the timing and
      position of leaf initiation are less well understood. Here we describe a gene
      from maize, terminal ear 1. Patterns of expression of this gene in the shoot and
      phenotypes of mutants indicate a role for terminal ear 1 in regulating leaf
      initiation. The tel gene product contains conserved RNA-binding motifs,
      indicating that it may function through an RNA-binding activity.

PMID- 9603519
TI  - Neonatal lesions of the medial temporal lobe disrupt prefrontal cortical
      regulation of striatal dopamine.
AB  - The effects of early brain damage are often, but not always, milder than the
      effects of comparable damage in adults, depending on the age at which injury
      occurred, the region of the brain damaged, and the brain functions involved.
      Studies of the impact of early brain damage have generally focused on functions
      primarily associated with the neural structures injured, even though the
      development and function of distant but interconnected neural systems might also
      show effects. Here we examine the regulation of striatal dopamine by the
      dorsolateral prefrontal cortex, in adult monkeys that had had either neonatal or
      adult lesions of the medial-temporal lobe and in normal animals. We use
      microdialysis to measure the dopamine response in the caudate nucleus after the
      infusion of amphetamine into the dorsolateral prefrontal cortex. Normal animals
      and those with adult lesions showed a reduction in dopamine overflow; in
      contrast, monkeys with neonatal lesions showed increased dopamine release. Thus,
      early injury to the primate medial-temporal lobe disrupts the normal regulation
      of striatal dopamine activity by the dorsolateral prefrontal cortex during
      adulthood. Early focal lesions may have substantial and long-lasting impacts on
      the function of a distant neural system.

PMID- 9603520
TI  - Control of spatial orientation in a mollusc.
AB  - The main function of postural nervous mechanisms in different species, from
      mollusc to man, is to counteract the force of gravity and stabilize body
      orientation in space. Here we investigate the basic principles of postural
      control in a simple animal model, the marine mollusc Clione limacina. When
      swimming, C. limacina maintains its vertical orientation because of the activity
      of the postural neuronal network. Driven by gravity-sensing organs (statocysts),
      the network causes postural corrections by producing tail flexions. To understand
      how this function occurs, we studied network activity by using a new method. We
      used an in vitro preparation that consisted of the central nervous system
      isolated with the statocysts. Output signals from the network (electrical
      activity of tail motor neurons) controlled an electrical motor which rotated the
      preparation in space. We analysed the activity of individual neurons involved in
      postural stabilization under opened or closed feedback loop. When we closed this
      artificial feedback loop, the network stabilized the vertical orientation of the
      preparation. This stabilization is based on the tendency of the network to
      minimize the difference between the activities of the two antagonistic groups of
      neurons, which are driven by orientation-dependent sensory inputs.

PMID- 9603521
TI  - Increased vulnerability to cocaine in mice lacking the serotonin-1B receptor.
AB  - There is increasing evidence that genetic factors can influence individual
      differences in vulnerability to drugs of abuse. Serotonin (5-hydroxytryptamine, 5
      HT), acting through many receptors can modulate the activity of neural reward
      pathways and thus the effects of various drugs of abuse. Here we examine the
      effects of cocaine in mice lacking one of the serotonin-receptor subtypes, the 5
      HT1B receptor. We show that mice lacking 5-HT1B display increased locomotor
      responses to cocaine and that they are more motivated to self-administer cocaine.
      We propose that even drug-naive 5-HT1B-knockout mice are in a behavioural and
      biochemical state that resembles that of wild-type mice sensitized to cocaine by
      repeated exposure to the drug. This altered state might be responsible for their
      increased vulnerability to cocaine.

PMID- 9603522
TI  - Frizzled signalling controls orientation of asymmetric sense organ precursor cell
      divisions in Drosophila.
AB  - During metazoan development, cell-fate diversity is brought about, in part, by
      asymmetric cell divisions. In Drosophila, bristle mechanosensory organs are
      composed of four different cells that originate from a single precursor cell, pI,
      after two rounds of asymmetric division. At each division, distinct fates are
      conferred on sister cells by the asymmetric segregation of Numb, a negative
      regulator of Notch signalling. Here we show that the orientation of the mitotic
      spindles and the localization of the Numb crescent follow a stereotyped pattern.
      Mitosis of pI is orientated parallel to the anteroposterior axis of the fly. We
      show that signalling mediated by the Frizzled receptor polarizes pI along this
      axis, thereby specifying the orientation of the mitotic spindle and positioning
      the Numb crescent. The mitoses of the two cells produced by mitosis of pI are
      orientated parallel and orthogonal, respectively, to the division axis of pI.
      This difference in cell-division orientation is largely independent of the
      identity of the secondary precursor cells, and is regulated by Frizzled
      independent mechanisms.

PMID- 9603523
TI  - The molecular elasticity of the extracellular matrix protein tenascin.
AB  - Extracellular matrix proteins are thought to provide a rigid mechanical anchor
      that supports and guides migrating and rolling cells. Here we examine the
      mechanical properties of the extracellular matrix protein tenascin by using
      atomic-force-microscopy techniques. Our results indicate that tenascin is an
      elastic protein. Single molecules of tenascin could be stretched to several times
      their resting length. Force-extension curves showed a saw-tooth pattern, with
      peaks of force at 137pN. These peaks were approximately 25 nm apart. Similar
      results have been obtained by study of titin. We also found similar results by
      studying recombinant tenascin fragments encompassing the 15 fibronectin type III
      domains of tenascin. This indicates that the extensibility of tenascin may be due
      to the stretch-induced unfolding of its fibronectin type III domains. Refolding
      of tenascin after stretching, observed when the force was reduced to near zero,
      showed a double-exponential recovery with time constants of 42 domains refolded
      per second and 0.5 domains per second. The former speed of refolding is more than
      twice as fast as any previously reported speed of refolding of a fibronectin type
      III domain. We suggest that the extensibility of the modular fibronectin type III
      region may be important in allowing tenascin-ligand bonds to persist over long
      extensions. These properties of fibronectin type III modules may be of widespread
      use in extracellular proteins containing such domain.

PMID- 9603524
TI  - Regulation of adenovirus alternative RNA splicing by dephosphorylation of SR
      proteins.
AB  - SR proteins are a family of essential splicing factors required for early
      recognition of splice sites during spliceosome assembly. They also function as
      alternative RNA splicing factors when overexpressed in vivo or added in excess to
      extracts in vitro. SR proteins are highly phosphorylated in vivo, a modification
      that is required for their function in spliceosome assembly and splicing
      catalysis. Here we show that SR proteins purified from late adenovirus-infected
      cells are inactivated as splicing enhancer or splicing repressor proteins by
      virus-induced dephosphorylation. We further show that the virus-encoded protein
      E4-ORF4 activates dephosphorylation by protein phosphatase 2A of HeLa SR proteins
      and converts their splicing properties into that of SR proteins purified from
      late adenovirus-infected cells. Taken together, our results suggest that E4-ORF4
      is an important factor controlling the temporal shift in adenovirus alternative
      RNA splicing. We conclude that alternative pre-mRNA splicing, like many other
      biological processes, is regulated by reversible protein phosphorylation.

PMID- 9603525
TI  - Function of TAF(II)-containing complex without TBP in transcription by RNA
      polymerase II.
AB  - Initiation of transcription of a gene from a core promoter region by RNA
      polymerase II requires the assembly of several initiation factors to form a
      preinitiation complex. Assembly of this complex is thought to be nucleated
      exclusively by the sequence-specific binding of the TFIID transcription factor
      complex, which is composed of the TATA-binding protein (TBP) and TBP-associated
      factors (TAF(II)s), to the different promoters. Here we isolate and characterize
      a new multiprotein complex that does not contain either TBP or a TBP-like factor
      but is composed of several TAF(II)s and other proteins. This complex can replace
      TFIID on both TATA-containing and TATA-lacking promoters in in vitro
      transcription assays. Moreover, an anti-TBP antibody that inhibits TBP- and TFIID
      dependent transcription does not inhibit activity of this new complex. These
      results indicate that TBP-free RNA polymerase II mediated transcription may be
      able to occur in mammalian cells and that multiple preinitiation complexes may
      play an important role in regulating gene expression.

PMID- 9603526
TI  - Future of proposed tobacco settlement looks hazy.

PMID- 9603527
TI  - Problems on the pathway from risk assessment to risk reduction.

PMID- 9603528
TI  - Blood pressure gene at the angiotensin I-converting enzyme locus: chronicle of a
      gene foretold.

PMID- 9603529
TI  - Evidence for association and genetic linkage of the angiotensin-converting enzyme
      locus with hypertension and blood pressure in men but not women in the Framingham
      Heart Study.
AB  - BACKGROUND: There is controversy regarding the association of the angiotensin
      converting enzyme deletion-insertion (ACE D/I) polymorphism with systemic
      hypertension and with blood pressure. We investigated these relations in a large
      population-based sample of men and women by using association and linkage
      analyses. METHODS AND RESULTS: The study sample consisted of 3095 participants in
      the Framingham Heart Study. Blood pressure measurements were obtained at regular
      examinations. The ACE D/I polymorphism was identified by using a polymerase chain
      reaction assay. In logistic regression analysis, the adjusted odds ratios for
      hypertension among men for the DD and DI genotypes were 1.59 (95% confidence
      interval [CI], 1.13 to 2.23) and 1.18 (95% CI, 0.87 to 1.62), respectively,
      versus II (chi2 P=.02). In women, adjusted odds ratios for the DD and DI
      genotypes were 1.00 (95% CI, 0.70 to 1.44) and 0.78 (95% CI, 0.56 to 1.09),
      respectively (P=.14). In linear regression analysis, there was an association of
      the ACE DD genotype with increased diastolic blood pressure in men (age-adjusted
      P=.03, multivariate-adjusted P=.14) but not women. Quantitative trait linkage
      analyses in 1044 pairs of siblings, by using both ACE D/I and a nearby
      microsatellite polymorphism of the human growth hormone gene, supported a role of
      the ACE locus in influencing blood pressure in men but not in women. CONCLUSIONS:
      In our large, population-based sample, there is evidence for association and
      genetic linkage of the ACE locus with hypertension and with diastolic blood
      pressure in men but not women. Our data support the hypothesis that ACE, or a
      nearby gene, is a sex-specific candidate gene for hypertension. Confirmatory
      studies in other large population-based samples are warranted.

PMID- 9603530
TI  - Variation in the region of the angiotensin-converting enzyme gene influences
      interindividual differences in blood pressure levels in young white males.
AB  - BACKGROUND: The renin-angiotensin system regulates blood pressure through its
      effects on vascular tone, renal hemodynamics, and renal sodium and fluid balance.
      METHODS AND RESULTS: Using data from a large population-based sample of 1488
      siblings having a mean age of 14.8 years and belonging to the youngest generation
      of 583 randomly ascertained three-generation pedigrees from Rochester, Minn, we
      carried out variance components-based linkage analyses to evaluate the
      contribution of variation in four renin-angiotensin system gene regions
      (angiotensinogen, renin, angiotensin I-converting enzyme, and angiotensin II
      receptor type 1) to interindividual variation in systolic, diastolic, and mean
      arterial pressure. We rejected the null hypothesis that allelic variation in the
      region of the angiotensin-converting enzyme (ACE) gene does not contribute to
      interindividual blood pressure variability. After conditioning on measured
      covariates, variation in this region accounted for 0%, 13% (P=0.04), and 16%
      (P=0.04) of the interindividual variance in systolic, diastolic, and mean
      arterial pressures, respectively. These estimates were even greater in a subset
      of subjects with a positive family history of hypertension (0%, 29% [P=0.005],
      and 32% [P<0.005], respectively). In sex-specific analyses, genetic variation in
      the region of the ACE gene significantly influenced interindividual blood
      pressure variation in males (37% for SBP [P=0.03], 38% for DBP [P=0.04], and 53%
      for MAP [P<0.005]) but not in females. CONCLUSIONS: Although it is possible that
      variation in a gene near the ACE gene may explain the observed results, knowledge
      about the physiological involvement of ACE in blood pressure regulation supports
      the proposition that the ACE gene itself influences blood pressure variability in
      a sex-specific manner.

PMID- 9603531
TI  - Angiotensin-converting enzyme DD genotype and cardiovascular disease in
      heterozygous familial hypercholesterolemia.
AB  - BACKGROUND: Controversy exists as to whether the deletion/deletion genotype (DD)
      of the ACE gene polymorphism increases the risk of myocardial infarction (MI).
      Studies have suggested that the ACE DD genotype is associated with increased
      plaque instability. We hypothesized that the ACE DD genotype may increase the
      risk of myocardial infarction and coronary heart disease (CHD) in patients with
      heterozygous familial hypercholesterolemia (FH) or familial defective
      apolipoprotein B-100 (FDB) who, as a group, are at high risk of having lipid-rich
      plaques in their coronary arteries. METHODS AND RESULTS: We determined the ACE
      genotypes and incidence of MI or surgical intervention for CHD in 213 adult
      patients with heterozygous FH or FDB. The incidence of MI in 35 male patients who
      carried the ACE DD genotype was 2.5 times that observed in male patients with the
      II or DI genotypes, and the incidence of CHD in male patients with the DD
      genotype was 2.2 times higher than in those who had ACE DI+II. The potential
      effects of ACE genotype on CHD could not be directly compared in female patients
      because of a disparity in the smoking history of the genotypic groups. From
      logistic regression analysis, the estimated odds ratio associated with the ACE DD
      genotype was 2.57 for MI and 2.21 for CHD adjusted for age, sex, and smoking
      history. CONCLUSIONS: The ACE DD genotype is associated with an increased risk of
      MI and CHD in patients with heterozygous FH or FDB. Determination of the ACE
      genotype in asymptomatic FH and FDB patients provides an additional means to
      identify those patients at greatest risk for the premature development of CHD.

PMID- 9603532
TI  - Effects of lowering average of below-average cholesterol levels on the
      progression of carotid atherosclerosis: results of the LIPID Atherosclerosis
      Substudy. LIPID Trial Research Group.
AB  - BACKGROUND: Cholesterol lowering in patients with above-average cholesterol
      levels has been shown to reduce the progression of atherosclerosis and lower the
      risk of coronary heart disease events. However, there has been uncertainty about
      the effects of cholesterol lowering in patients with average or below-average
      cholesterol levels. METHODS AND RESULTS: In this study, 522 patients with a
      history of myocardial infarction or unstable angina and with baseline levels of
      total cholesterol between 4 and 7 mmol/L (mean, 5.7 mmol/L) were randomized to
      treatment with a low fat diet plus pravastatin (40 mg daily) or to a low fat diet
      plus placebo. Treatment with pravastatin reduced the levels of total cholesterol
      by 19%, LDL cholesterol by 27%, apolipoprotein B by 19%, and triglycerides by 13%
      (all 2P<.0001) and increased apolipoprotein A1 and HDL cholesterol levels by 4%
      (both 2P<.0005), in comparison with placebo. Carotid atherosclerosis was assessed
      from B-mode ultrasound measurements of the common carotid artery. After 4 years,
      mean carotid wall thickness had increased by 0.048 mm (SE=0.01) in the placebo
      group and declined by 0.014 mm in the pravastatin-treated group (SE=0.01) (2P for
      difference <.0001). The effect of treatment on wall thickness was similar in
      three groups classified by tertiles of total cholesterol at baseline, with mean
      levels of 4.8, 5.7, and 6.6 mmol/L, respectively (2P for interaction >.8).
      CONCLUSIONS: Treatment with pravastatin reduced the development of carotid
      atherosclerosis among patients with coronary heart disease and a wide range of
      pretreatment cholesterol levels. Treatment with this agent prevented any
      detectable increase in carotid wall thickening over 4 years of follow-up.

PMID- 9603533
TI  - Role of the preaxillary flora in pacemaker infections: a prospective study.
AB  - BACKGROUND: Infection remains a severe complication after pacemaker implantation.
      The purpose of our prospective study was to evaluate the role of the local
      bacteriologic flora in its occurrence. METHODS AND RESULTS: Specimens were
      collected at the site of implantation for culture from the skin and the pocket
      before and after insertion in a consecutive series of patients who underwent
      elective permanent pacemaker implantation. Microorganisms isolated both at the
      time of insertion and of any potentially infective complication were compared by
      using conventional speciation and ribotyping. There were 103 patients (67 men and
      36 women) whose age ranged from 16 to 93 years (mean+/-SD, 67+/-15). At the time
      of pacemaker implantation, a total of 267 isolates were identified. The majority
      (85%) were staphylococci. During a mean follow-up of 16.5 months (range, 1 to
      24), infection occurred in four patients (3.9%). In two of them, an isolate of
      Staphylococcus schleiferi was recognized by molecular method as identical to the
      one previously found in the pacemaker pocket. In one patient, Staphylococcus
      aureus, an organism that was absent at the time of pacemaker insertion, was
      isolated. In another patient, a Staphylococcus epidermidis was identified both at
      the time of pacemaker insertion and when erosion occurred; however, their
      antibiotic resistance profiles were different. CONCLUSIONS: This study strongly
      supports the hypothesis that pacemaker-related infections are mainly due to local
      contamination during implantation. S schleiferi appears to play an underestimated
      role in infectious colonization of implanted biomaterials and should be regarded
      as an important opportunistic pathogen.

PMID- 9603534
TI  - Antibiotic prophylaxis for permanent pacemaker implantation: a meta-analysis.
AB  - BACKGROUND: Infection remains a serious complication after permanent pacemaker
      implantation. Antibiotic prophylaxis is frequently prescribed at the time of
      insertion to reduce its incidence, although results of well-designed, controlled
      studies are lacking. METHODS AND RESULTS: We performed a meta-analysis of all
      available randomized trials to evaluate the effectiveness of antibiotic
      prophylaxis to reduce infection rates after permanent pacemaker implantation.
      Reports of trials were identified through a Medline, Embase, Current Contents,
      and an extensive bibliography search. Trials that met the following criteria were
      included: (1) prospective, randomized, controlled, open or blind trials; (2)
      patients assigned to a systemic antibiotic group or a control group; (3) end
      point events related to any infection after pacemaker implantation: wound
      infection, septicemia, pocket abscess, purulent secretion, right infective
      endocarditis, inflammatory signs, a positive culture, septic pulmonary embolism,
      or repeat operation for an infective complication. Seven trials met the inclusion
      criteria. They included 2023 patients with established permanent pacemaker
      implantation (new implants or replacements). The incidence of end point events in
      control groups ranged from 0% to 12%. The meta-analysis suggested a consistent
      protective effect of antibiotic pretreatment (P=.0046; common odds ratio: 0.256,
      95% confidence interval: 0.10 to 0.656). CONCLUSIONS: Results of the present meta
      analysis suggest that systemic antibiotic prophylaxis significantly reduces the
      incidence of potentially serious infective complications after permanent
      pacemaker implantation. They support the use of prophylactic antibiotics at the
      time of pacemaker insertion to prevent short-term pocket infection, skin erosion
      or septicemia.

PMID- 9603535
TI  - Contrast media-enhanced magnetic resonance imaging visualizes myocardial changes
      in the course of viral myocarditis.
AB  - BACKGROUND: The course of tissue changes in acute myocarditis in humans is not
      well understood. Diagnostic tools currently available are unsatisfactory. We
      tested the hypothesis that inflammation is reflected by signal changes in
      contrast-enhanced magnetic resonance imaging (MRI). METHODS AND RESULTS: We
      assessed 44 consecutive patients with symptoms of acute myocarditis. Nineteen
      patients met the inclusion criteria revealing ECG changes, reduced myocardial
      function, elevated creatine kinase, positive troponin T, serological evidence for
      acute viral infection, exclusion of coronary heart disease, and positive
      antimyosin scintigraphy. We studied these patients on days 2, 7, 14, 28, and 84
      after the onset of symptoms. We obtained ECG-triggered, T1-weighted images before
      and after application of 0.1 mmol/kg gadolinium. We measured the global relative
      signal enhancement of the left ventricular myocardium related to skeletal muscle
      and compared it with measurements in 18 volunteers. The global relative
      enhancement was higher in patients on days 2 (4.8+/-0.3 [mean+/-SE] versus 2.5+/
      0.2; P<.0001); 7 (4.7+/-0.5, P<.0001); 14 (4.6+/-0.5, P<.0002); and 28 (3.9+/
      0.4, P=.009) but not on day 84 (3.1+/-0.3; P=NS). On day 2, the enhancement was
      focal, whereas at later time points, the enhancement was diffuse. In patients
      with evidence of ongoing disease, the values remained elevated. CONCLUSIONS:
      Acute myocarditis evolves from a focal to a disseminated process during the first
      2 weeks after onset of symptoms. Contrast media-enhanced MRI visualizes the
      localization, activity, and extent of inflammation and may serve as a powerful
      noninvasive diagnostic tool in acute myocarditis.

PMID- 9603536
TI  - Evolution and resolution of long-term cardiac memory.
AB  - BACKGROUND: Cardiac memory (CM) refers to T-wave changes induced by ventricular
      pacing or arrhythmia that accumulate in magnitude and duration with repeated
      episodes of abnormal activation. We report herein the kinetics of long-term CM
      and its association with the ventricular action potential. METHODS AND RESULTS:
      Dogs were paced from the ventricles at rates of 110 to 120 bpm for approximately
      3 weeks. CM characterized by gradual sinus rhythm T vector rotation toward the
      paced QRS vector evolved in all dogs regardless of pacing site (left ventricular
      [LV] anterior apex or base, posterior LV, or right ventricular free wall).
      Cardiac hemodynamics and myocardial flow (microsphere studies) were unaltered by
      the pacing. Recovery time for the memory T wave to return to control increased
      with duration of the previous pacing. The protein synthesis inhibitor
      cycloheximide markedly (P<.05) and reproducibly attenuated evolution of CM. When
      pacing was performed from the atrium, CM did not occur. Standard microelectrode
      techniques were used to study action potential from the LV free wall of control
      and CM dogs. CM was associated with increased action potential duration in
      epicardial and endocardial but not midmyocardial cells, significantly altering
      the transmyocardial gradient for repolarization. CONCLUSIONS: CM is a dynamic
      process for which the final T vector is predicted by the paced QRS vector and
      which is associated with significant changes in epicardial and endocardial but
      not midmyocardial cell action potential duration, such that the transmural
      gradient of repolarization is altered. It is unaccompanied by evidence of altered
      hemodynamics or flow, requires a change in pathway of activation, and appears to
      require new protein synthesis.

PMID- 9603537
TI  - Beta3-integrins rather than beta1-integrins dominate integrin-matrix interactions
      involved in postinjury smooth muscle cell migration.
AB  - BACKGROUND: Smooth muscle cell (SMC) migration is a vital component in the
      response of the arterial wall to revascularization injury. Cell surface integrin
      extracellular matrix interactions are essential for cell migration. SMCs express
      both beta1- and beta3-integrins. In this study, we examined the relative
      functional roles of beta1- and beta3-integrin-matrix interactions in postinjury
      SMC migration. METHODS AND RESULTS: Flow cytometry and fluorescence microscopy of
      migrating SMCs immunostained with anti-beta1 and anti-alpha(v)beta3/5 antibodies
      (Abs) revealed expression of both beta1- and beta3-integrins, with beta1 observed
      as linear streaks and beta3 found in focal contacts. In a scrape-wound migration
      assay, anti-beta1 Abs (92.0+/-10.7% of control, P=.1) and 0.5 mmol/L linear RGD
      (105+/-5% of control, P=.2) did not alter SMC migration at 48 hours after injury.
      Beta3-blockade, however, via Abs (anti-beta3/5 35.7+/-4.5% of control, anti-beta3
      61+/-12% of control, both P<.001) and cyclic RGD (0.5 mmol/L) (12+/-10% of
      control, P<.001) decreased migration. Neither beta1- nor beta3-inhibition altered
      postinjury [3H]thymidine incorporation. In the rat carotid injury model, local
      adventitial polymer-based delivery of radiolabeled linear or cyclic RGD led to
      uptake and retention of label, for both peptides, over a 72-hour period after
      injury. Local arterial wall beta1-blockade via polymer-based delivery of linear
      RGD had no effect on SMC migration at 4.5 days (11.5+/-3.2 versus 12.8 SMCs per
      x600 field [control], P=.6) or on neointimal thickening at 14 days (I/M area
      ratio, 0.664+/-0.328 versus 1.179+/-0.324 [control], P=.6) after injury. In
      contrast, local beta3-blockade via cRGD limited migration (0.8+/-0.8 versus
      12.8+/-4.4 SMCs per x600 field [control], P<.01) and thickening (I/M area ratio,
      0.004+/-0.008 versus 1.179+/-0.324 [control], P<.01). CONCLUSIONS: In postinjury
      migrating SMCs, beta3- rather than beta1-integrin-matrix interactions are of
      greater functional significance in adhesive processes essential for SMC migration
      in vitro and in vivo. Blockade of dominant SMC integrin (beta3)-matrix
      interactions may be a valuable approach for limiting injury-induced SMC migration
      and late arterial renarrowing.

PMID- 9603538
TI  - Effects of procainamide on wave-front dynamics during ventricular fibrillation in
      open-chest dogs.
AB  - BACKGROUND: There is increasing evidence that both functional reentrant wave
      fronts and multiple wavelets are present during ventricular fibrillation (VF).
      However, the effects of procainamide on the characteristics of activation waves
      during VF are poorly understood. METHODS AND RESULTS: Seven dogs were studied;
      six underwent subendocardial chemical ablation procedures. A plaque with 317 to
      480 bipolar electrodes was sutured to the right ventricular free wall, and the
      patterns of activation were registered with a computerized mapping system. VF was
      electrically induced, and the patterns of activation were registered at baseline
      and during procainamide infusion (serum concentration, 9.3+/-1.9 microg/mL).
      Among the six dogs that had their subendocardium ablated, reentrant wave fronts
      were present in 6 of the 108 runs of VF at baseline and in 6 of the 100 runs of
      VF during procainamide infusion. By analyzing the wave fronts, we found that the
      cycle length, refractory period, conduction velocity, and wavelength at baseline
      were 101+/-9 ms, 54+/-5 ms, 0.93+/-0.21 mm/ms, and 51+/-16 mm, respectively, and
      during procainamide infusion, values became 125+/-11 ms (P<.001), 119+/-7 ms
      (P<.001), 0.42+/-0.02 mm/ms (P<.001), and 50+/-4 mm (P=.8), respectively. The
      vast majority of the activation waves do not form organized reentry. These
      activation waves broke up more frequently at baseline than during procainamide
      administration. The number of activation waves was 7.25+/-1.39 s(-1) x cm(-2) at
      baseline and 4.45+/-1.80 s(-1) x cm(-2) during procainamide administration
      (P<.001). The dog without subendocardial ablation had similar results.
      CONCLUSIONS: Procainamide decreases the number of wavelets during VF by
      preventing spontaneous wave breaks. This represents a novel mechanism of
      antiarrhythmic drug action.

PMID- 9603539
TI  - Prediction of coronary heart disease using risk factor categories.
AB  - BACKGROUND: The objective of this study was to examine the association of Joint
      National Committee (JNC-V) blood pressure and National Cholesterol Education
      Program (NCEP) cholesterol categories with coronary heart disease (CHD) risk, to
      incorporate them into coronary prediction algorithms, and to compare the
      discrimination properties of this approach with other noncategorical prediction
      functions. METHODS AND RESULTS: This work was designed as a prospective, single
      center study in the setting of a community-based cohort. The patients were 2489
      men and 2856 women 30 to 74 years old at baseline with 12 years of follow-up.
      During the 12 years of follow-up, a total of 383 men and 227 women developed CHD,
      which was significantly associated with categories of blood pressure, total
      cholesterol, LDL cholesterol, and HDL cholesterol (all P<.001). Sex-specific
      prediction equations were formulated to predict CHD risk according to age,
      diabetes, smoking, JNC-V blood pressure categories, and NCEP total cholesterol
      and LDL cholesterol categories. The accuracy of this categorical approach was
      found to be comparable to CHD prediction when the continuous variables themselves
      were used. After adjustment for other factors, approximately 28% of CHD events in
      men and 29% in women were attributable to blood pressure levels that exceeded
      high normal (> or =130/85). The corresponding multivariable-adjusted attributable
      risk percent associated with elevated total cholesterol (> or =200 mg/dL) was 27%
      in men and 34% in women. CONCLUSIONS: Recommended guidelines of blood pressure,
      total cholesterol, and LDL cholesterol effectively predict CHD risk in a middle
      aged white population sample. A simple coronary disease prediction algorithm was
      developed using categorical variables, which allows physicians to predict
      multivariate CHD risk in patients without overt CHD.

PMID- 9603540
TI  - Medical and cellular implications of stunning, hibernation, and preconditioning:
      an NHLBI workshop.

PMID- 9603541
TI  - Images in cardiovascular medicine. Giant coronary fistula.

PMID- 9603542
TI  - Images in cardiovascular medicine. Noninvasive diagnosis of anomalous origin of
      the left main coronary artery from the pulmonary artery.

PMID- 9603543
TI  - Passive smoking and coronary heart disease in women.

PMID- 9603544
TI  - A prospective study of passive smoking and coronary heart disease.

PMID- 9603545
TI  - Passive smoking and coronary heart disease.

PMID- 9603546
TI  - Passive smoking and coronary heart disease.

PMID- 9603547
TI  - Angiotensin II and coronary sympathetic vasodilation.

PMID- 9603548
TI  - Functional evaluation of lipid-lowering therapy by pravastatin.

PMID- 9603549
TI  - Primary prevention of coronary heart disease: guidance from Framingham: a
      statement for healthcare professionals from the AHA Task Force on Risk Reduction.
      American Heart Association.

PMID- 9603550
TI  - Controversies in the diagnosis and management of craniosynostosis: a panel
      discussion.
AB  - This introductory article summarizes and comments on a group of four papers based
      in part on a panel discussion of craniosynostosis (CS) held at the 53rd annual
      meeting of the American Cleft Palate-Craniofacial Association. The purpose of
      this panel was to review the differential diagnosis of CS and the evidence for
      increased intracranial pressure (ICP) and developmental problems in CS patients.
      First, a correct diagnosis must be made, with true synostosis being
      differentiated from positional deformities and other normal variants. Second,
      medical indications must be balanced against the risks of operating on CS
      patients. Release of fused sutures is commonly undertaken to avoid increased ICP,
      although studies of ICP in infants and children with CS are hampered by a lack of
      normative data and by difficulties with measurement techniques. A subgroup of
      children with isolated craniosynostosis may have increased ICP, which can be
      deleterious to brain function. Longitudinal studies of children with isolated CS
      suggest an increased risk of mental retardation and learning disorders; surgical
      release of the suture may not diminish this risk. Patients with metopic suture
      fusion appear to be particularly at risk. These findings must be confirmed with a
      larger sample size. These uncertainties raise ethical issues and complicate
      medical decision-making for the infant with CS. A trusting and truthful
      relationship between the parents and the professional is necessary for a balanced
      discussion of the best interests of the child. All patients with confirmed
      synostosis should be followed for evidence of progressive deformity, intracranial
      hypertension, and neurodevelopmental problems.

PMID- 9603551
TI  - Intracranial pressure in single-suture craniosynostosis.
AB  - In this paper, we review the incidence of increased intracranial pressure in
      children with single-suture craniosynostosis. The major studies in this area are
      presented, along with their limitations. A rational treatment plan including
      multidisciplinary team management is recommended. All patients with proven
      synostosis should be followed closely, whether or not surgery is chosen.
      Continued clinical and basic science research are necessary to further clarify
      the ramifications of asymptomatic elevations of intracranial pressure in these
      patients.

PMID- 9603552
TI  - Mental development and learning disorders in children with single suture
      craniosynostosis.
AB  - OBJECTIVE: This study examined the global intellectual development and
      presence/absence of learning disorders in children with nonsyndromic metopic,
      sagittal, and unilateral coronal synostosis who had early surgery (under 1 year
      of age), late surgery (over 1 year of age), or no surgery to correct the
      synostosis across three time periods. DESIGN: The design was longitudinal.
      Children were assessed at initial team evaluation, 1 year after surgery or
      initial evaluation if surgery was not performed, and annually thereafter.
      PARTICIPANTS: Participants included 84 consecutively evaluated patients. Seventy
      two children were evaluated at Time 1 (T1), 8 months; 57 at Time 2 (T2), 21
      months; and 39 at Time 3 (T3), 50 months. Data on learning disorders or mental
      retardation were available on 34 children who were school age. MAIN OUTCOME
      MEASURES: The Mental Development Index from the Bayley Scales of Infant
      Development was the main outcome measure for T1 and T2. The General Cognitive
      Index from the McCarthy Scales of Children's Abilities was the main outcome
      measure for T3. Learning disorders were determined from school and clinical
      records. RESULTS: Repeated measures analyses of variance found no statistical
      differences in the development of children based on diagnosis or surgical status
      across time. Base rate of mental retardation at T1 was consistent with normative
      data; however, the incidence of retardation was two to three times the expected
      rate at T2 and T3. Learning disorders were present in 47% of school-age children
      who were not retarded. Chi-square analysis showed no significant differences
      between rates of retardation or learning disorders based on surgical status.
      CONCLUSIONS: Most children with nonsyndromic craniosynostosis obtain
      developmental quotients within the normal range in infancy. Rates of retardation
      may increase relative to normative expectations as children mature. A high rate
      of learning disorders was identified. Results are preliminary due to sample size.

PMID- 9603553
TI  - The differential diagnosis of abnormal head shapes: separating craniosynostosis
      from positional deformities and normal variants.
AB  - The correct differential diagnosis of an abnormal head shape in an infant or a
      child is vital to the management of this common condition. Establishing the
      presence of craniosynostosis, which warrants surgical correction, versus non
      synostotic causes of head deformity, which do not, is not always straightforward.
      This paper deals with three groups of abnormal head shape that may cause
      diagnostic confusion: the spectrum of metopic synostosis; the dolichocephaly of
      prematurity versus sagittal synostosis; and the differential diagnosis of
      plagiocephaly. Special emphasis has been placed on the problem of posterior
      plagiocephaly, in the light of recent evidence demonstrating that lambdoid
      synostosis has been overdiagnosed. Metopic synostosis presents as a wide spectrum
      of severity. Although only severe forms of the disorder are corrected surgically,
      all cases should be monitored for evidence of developmental problems. The
      dolichocephalic head shape of preterm infants is non-synostotic in origin and is
      managed nonsurgically. The scaphocephalic head shape resulting from sagittal
      synostosis requires surgical intervention for correction. Posterior plagiocephaly
      may be due to unilambdoid synostosis or positional molding, which have very
      different clinical and imaging features. True lambdoid synostosis is rare. Most
      cases of posterior plagiocephaly are due to positional molding, which can usually
      be managed nonsurgically. Regardless of the suture(s) involved, all children with
      confirmed craniosynostosis should be monitored for increased intracranial
      pressure and developmental problems.

PMID- 9603554
TI  - The treatment of craniosynostosis: an ethical perspective.
AB  - The parents of children with craniofacial deformity have expectations that cannot
      always be reasonably met in a world of clinical uncertainty. In order to bridge
      the "reality gap," the members of the cranofacial team must be open and honest in
      discussing the known harms and benefits of a proposed treatment, so that a
      relationship of trust evolves between the health care professional and the
      patient/parent. It is only through this trust that a truthful implementation of
      consent, within its moral framework, can be achieved. This, in turn, requires an
      analysis of the outcomes of the various options for treatment as well as evidence
      that the cranofacial team is able to provide high standards of care. All this
      leads to the ethical imperative of respecting the right of parents to make an
      informed choice and allowing them to see that their child is treated in a way
      that provides maximum benefit and minimum harm.

PMID- 9603555
TI  - Temporal characteristics of velopharyngeal function in children.
AB  - OBJECTIVE: This investigation was designed to examine the performance of children
      with normal speech on temporal aspects of aerodynamic tasks related to
      velopharyngeal closure. DESIGN: The investigation was a descriptive evaluation of
      variability in aerodynamic features related to velopharyngeal function during
      multiple repetitions of the word "hamper." SETTING: Children without speech or
      velopharyngeal difficulties were seen in an experimental laboratory setting for
      the evaluation procedures. PARTICIPANTS: Twenty-seven subjects were recruited for
      the experiment. Three subjects were rejected because of behavioral difficulties,
      and the remaining 24 subjects were subdivided into 4 groups of 6 children (3
      males and 3 females) aged 3, 6, 9, and 12 years. The children, who were from
      local schools and day care centers, volunteered to participate in the experiment.
      All of the children had age-appropriate speech, language, and hearing abilities,
      as determined by screening tests administered by one of the examiners (L.T.).
      MAIN OUTCOME MEASURES: Mean and variability of pressure-flow measures of peak
      intraoral air pressure and peak nasal airflow and the temporal measures
      accompanying each air pressure or airflow pulse were evaluated for the age groups
      of children examined in the experiment. RESULTS: The aerodynamic procedures
      employed to evaluate velopharyngeal closure during speech were reliable for use
      with young children. There was a numerical trend toward decreased duration of the
      temporal parameters with increasing age. Thus, children demonstrated durational
      values similar to those previously reported for normal-speaking adults. In
      general, peak oral air pressure and nasal airflow values were like those of
      previous investigations and demonstrated low variability across all age groups of
      children tested. CONCLUSIONS: The data from the present investigation provide a
      preliminary base for comparison of temporal features of velopharyngeal closure
      for the aerodynamic evaluation of children with impaired velopharyngeal function.

PMID- 9603556
TI  - Short-term cost-effectiveness analysis of presurgical orthopedic treatment in
      children with complete unilateral cleft lip and palate.
AB  - OBJECTIVE: The aim of this article was to investigate cost-effectiveness in cleft
      palate treatment using cost-effectiveness of presurgical orthopedic treatment
      (PSOT) as an example. DESIGN: A three-center randomized clinical trial compared
      PSOT with non-PSOT for children with unilateral cleft lip and palate (UCLP,
      n=52). PATIENTS: The inclusion criteria for the trial were: complete UCLP, no
      other malformations, born at term, both parents Caucasian, trial entrance
      preferably within 2 weeks after birth, and informed consent by the parents.
      INTERVENTIONS: PSOT was performed by means of a passive plate according to Hotz
      and Gnoinski. MAIN OUTCOME MEASURE: The short-term cost-effectiveness of PSOT was
      based on the time taken for the surgical lip closure procedure. Medical and
      nonmedical costs until surgical lip closure at 18 weeks of age were analyzed.
      RESULTS: The durations of the surgical lip closure procedures did not differ
      significantly (57.2 minutes for PSOT and 56.4 minutes for non-PSOT). The mean
      medical cost for PSOT treatment was US$852. The non-PSOT treatment group had a
      significantly different mean medical cost (US$304). Mean travel costs and
      indirect nonmedical costs were US$128 and US$231 for PSOT and US$79 and US$130
      for non-PSOT, respectively. CONCLUSIONS: The combination of a clinical trial and
      an economic evaluation makes it possible to relate effects to costs involved in
      treatment alternatives. Longer-term costs and effects will be incorporated into
      an extended cost-effectiveness analysis to determine the cost-effectiveness of
      PSOT.

PMID- 9603557
TI  - Effects of presurgical orthopedic treatment in infants with complete bilateral
      cleft lip and palate.
AB  - OBJECTIVE: To align the protruding premaxilla in infants with bilateral cleft lip
      and palate (BCLP), an intraoral appliance (i.e., Hotz plate) and an extraoral
      appliance consisting of a band covering the head and elastics are used as a
      presurgical orthopedic treatment in our clinic. The aim of this study was to
      analyze the configuration and position of the premaxilla and the vomer in infants
      with BCLP and to investigate the factors generating deviation and bending of the
      vomer and twisting of the premaxilla. PATIENTS: Palatal casts were obtained
      serially from 10 infants with complete BCLP from 1 to 3 months of age.
      MEASUREMENTS: These casts were automatically measured using a highly accurate
      contact-type measuring apparatus. After three-dimensional wire frame models
      generated from the serial casts were automatically superimposed, the magnitude
      and direction of the shift were calculated. A discriminant analysis was used for
      investigation of predictor variables generating the twisting or bending vomer.
      RESULTS AND CONCLUSIONS: The vomer was found to be bent in two infants and the
      premaxilla was twisted in three infants. In the infants whose vomers were bent,
      the magnitude of the posterior shift of the premaxilla was greater than that of
      the inferior shift. A discriminant analysis indicated that at 1 month of age, a
      greater inclination and a smaller deviation of the vomer and a longer distance
      between the cleft edges of the lateral segments had a tendency to be associated
      with bending of the vomer or twisting of the premaxilla.

PMID- 9603558
TI  - Maxillary arch dimensions in bilateral cleft lip and palate from birth until four
      years of age in boys.
AB  - OBJECTIVE: To describe the development of maxillary arch dimensions in children
      with bilateral cleft lip and palate (BCLP) during the first 4 years of life and
      to compare it with that in noncleft children. DESIGN: This was a retrospective,
      mixed-longitudinal study. SETTING: The study was conducted at the Cleft Palate
      Center of the University Hospital of Nijmegen. SUBJECTS: The sample consisted of
      26 boys with BCLP who were born between 1976 and 1990 and treated at the
      University Hospital of Nijmegen. Data for a control group of 34 noncleft boys
      were collected at the University Hospital of Amsterdam. METHOD: Palatal arch
      dimensions were digitized on dental casts. A comparison between BCLP and noncleft
      dimensions was made at fixed time intervals. RESULTS: At birth, anterior and
      posterior arch widths as well as arch depths were significantly larger in
      children with BCLP. After 7 months (lip closure), anterior arch width and arch
      depth diminished considerably in the cleft group. After 12 months (palatoplasty),
      a slight decrease in posterior arch width was observed, and arch depths showed
      slight catch-up growth. At 4 years of age, anterior arch width was significantly
      narrower and anterior arch depth was shorter in children with BCLP than in
      control subjects. Posterior arch width was significantly wider. CONCLUSIONS:
      During the first 4 years of life, maxillary arch dimensions in children with BCLP
      show a unique development that is significantly different from that in noncleft
      children.

PMID- 9603559
TI  - Changes in craniofacial development due to modifications of the treatment of
      unilateral cleft lip and palate.
AB  - OBJECTIVE: The objective of this study was to evaluate the craniofacial
      morphology of children with unilateral cleft lip and palate (UCLP) resulting from
      differing management protocols practiced in Prague from 1945 to 1976. DESIGN: The
      craniofacial morphologies of four groups of patients were compared. Two groups
      were assessed retrospectively (individuals born from 1945 to 1963), and two
      groups were followed on a longitudinal basis (individuals born from 1966 to
      1976). SETTING: The study was conducted at the Cleft Lip and Palate Center at the
      Department of Plastic Surgery, Prague, which has a catchment area population of 6
      million. PATIENTS: The subjects were a consecutive series of adult males (n = 84)
      who had complete UCLP without associated malformations. INTERVENTIONS: Patients
      born from 1945 to 1955 did not receive centralized orthodontic therapy. From 1945
      to 1965, the alveolar process in the area of the cleft was not surgically
      repaired. Primary bone grafting was used for the group born from 1965 to 1972,
      and primary periosteoplasty was used in the subsequent period. Throughout the
      period covered by the study, the palate was operated on by pushback and
      pharyngeal flap surgery. From 1945 to 1965, the lip was repaired initially
      according to Veau, and later according to Tennison and Randall, and during this
      time, fixed appliances were used for orthodontic treatment. RESULTS: The results
      for the period from 1945 to 1955 are characterized by mandibular overclosure with
      anterior crossbite. Centralized orthodontic treatment in the later period
      improved sagittal jaw relations due to the posterior displacement of the mandible
      and an edge-to-edge bite was attained, but maxillary retrusion was unchanged.
      Primary bone grafting increased retrusion of the maxilla, which was compensated
      by further posterior displacement of the mandible. An edge-to-edge bite was also
      obtained. Primary periosteoplasty reduced maxillary retrusion, and the marked
      proclination of the upper dentoalveolar component with fixed appliances resulted
      in a positive overjet. It was no longer necessary to push the mandible back to
      the extent required in bone grafting. CONCLUSION: Effective orthodontic treatment
      made the greatest contribution to improved facial development. It allowed
      compensation of maxillary retrusion by changes in the position of the mandible or
      by proclination of the upper dentoalveolar component with fixed appliances. The
      applied surgical methods using primary bone grafting caused deterioration of the
      anterior growth of the maxilla.

PMID- 9603560
TI  - The oral health of children with clefts--a review.
AB  - A review of the studies of the caries prevalence and periodontal health of
      patients with cleft lip and palate (CLP) revealed that only five investigations
      of caries prevalence in CLP patients included children. One reported that CLP
      children did not have a higher caries prevalence in the permanent dentition,
      whereas more recent studies have reported a higher caries prevalence in both the
      primary and permanent dentitions of CLP children than in those of noncleft
      children. However, there is wide variation in the teeth examined and the method
      of presenting data on caries prevalence. Six papers have reported on the
      periodontal health of adult CLP patients, and only one has done so on that of
      children. The adult CLP patients had poorer oral hygiene and more gingivitis, but
      there is no conclusive evidence that they have a higher risk of developing
      periodontal disease. No data on the oral hygiene of CLP children were available,
      but it has been emphasized that they have significantly more gingivitis than
      noncleft children, especially in the maxillary anterior teeth.

PMID- 9603561
TI  - Birth weight, body length, and cranial circumference in newborns with cleft lip
      or palate.
AB  - OBJECTIVE: This paper reports on birth weight, body length, body mass index, and
      cranial circumference at birth of infants with cleft lip and/or palate born
      between 1973 and 1992. METHODS: Data were obtained from two nationwide Swedish
      health registries. Infants with syndromes, twins, and infants with immigrant
      parentage were excluded from the study. Comparisons were made with all singleton
      births with the same exclusion criteria (n = 2,031,140). RESULTS: The body
      dimensions of infants with isolated cleft lip (n = 865) were found not to differ
      from those of control subjects, but infants with isolated cleft palate (n = 811)
      or cleft lip and palate (n = 1139) were found to be lighter and shorter than
      control subjects. Also, infants with the Pierre Robin sequence (n = 121) had a
      tendency to be lighter and shorter than control subjects, but these differences
      did not reach statistical significance despite the large study population.

PMID- 9603562
TI  - Mobius syndrome with dental involvement: a case report and literature review.
AB  - The clinicopathological findings on a 17-year-old female with the Mobius/Moebius
      syndrome are reported. The signs and symptoms of this neuromuscular condition
      include congenital bilateral or unilateral palsies of the facial and abducens
      cranial nerves and a broad scope of multisystem abnormalities. A case of
      unilateral deficiencies of cranial nerves VI and VII, congenital ectrodactyly of
      toes, and multiple congenitally missing primary and permanent teeth is reported.
      A review of the literature reveals various ideas regarding the diversity of
      symptoms and the etiology of the syndrome. The purpose of this article is to
      report oral manifestations, such as congenitally missing teeth, associated with
      Mobius syndrome.

PMID- 9603564
TI  - Are women's health needs really "special"?

PMID- 9603563
TI  - Median cleft of the lower lip associated with lip pits and cleft of the lip and
      palate.
AB  - OBJECTIVE: In this case report, we present an unusual combination of three
      congenital malformations: median cleft of the lower lip, lip pits, and unilateral
      cleft of the lip and palate without familial occurrence. CONCLUSIONS: From an
      etiological point of view, this combination of malformations could have happened
      during the late embryogenic period. Why this combination is uncommon is not
      known.

PMID- 9603565
TI  - Patient satisfaction and outcomes in alcohol and drug abuse treatment.

PMID- 9603566
TI  - Use of a new outcome scale to determine best practices.

PMID- 9603567
TI  - Implementing psychosocial rehabilitation with long-term patients in a public
      psychiatric hospital.

PMID- 9603568
TI  - An open letter to utilization review workers.

PMID- 9603569
TI  - Mothers with mental illness: I. The competing demands of parenting and living
      with mental illness.
AB  - OBJECTIVE: The purpose of this study is to understand the parenting experiences
      of women with mental illness from the perspectives of mothers and case managers
      employed by the state department of mental health. METHODS: Six focus groups of
      mothers and five focus groups of case managers met to discuss the problems facing
      mothers with mental illness and to recommend solutions. Focus-group transcripts
      were coded and items grouped by themes in qualitative analyses to explore the
      conflicts mothers face in meeting the dual challenges of parenting and living
      with mental illness. RESULTS: Mothers and case managers identified sources of
      conflict in four thematic categories: the stigma of mental illness, day-to-day
      parenting, managing mental illness, and custody of and contact with children.
      CONCLUSIONS: Many of the issues of mothers with mental illness are generic to all
      parents; others are specific to the situation of living with mental illness.
      Mothers with mental illness must play a role in developing standards for clinical
      care and the research agenda in this area.

PMID- 9603570
TI  - Mothers with mental illness: II. Family relationships and the context of
      parenting.
AB  - OBJECTIVE: This study explores the experiences of mothers with mental illness
      regarding their family relationships. METHODS: Six focus groups of mothers with
      mental illness and five focus groups of case managers met to discuss problems
      facing mothers with mental illness and to recommend solutions. Focus groups were
      audiotaped, and transcripts were coded and analyzed qualitatively to describe
      ways in which husbands and partners, grandparents, and other family members
      contribute to the context of parenting for mothers with mental illness. RESULTS:
      Mothers with mental illness and case managers described a range of relationships
      and attitudes of family members and provided examples of the ways in which family
      members contribute both positively and negatively to parenting. CONCLUSIONS:
      Although family members may seem to be natural supports for mothers with mental
      illness, their involvement in the context of parenting may not be entirely
      positive. The contributions of family members to the context of parenting for
      mothers with mental illness must be considered by treatment providers if
      unintentional negative outcomes are to be avoided.

PMID- 9603572
TI  - Duty-related and sexual stress in the etiology of PTSD among women veterans who
      seek treatment.
AB  - OBJECTIVE: The stressful experiences of women serving in the military have been a
      focus of increasing concern. A model of the impact of stress related to military
      duty and stress related to sexual abuse and harassment on the development of
      posttraumatic stress disorder (PTSD) among female veterans was evaluated.
      METHODS: Structural equation modeling was applied to data from 327 women treated
      in a VA clinical program for women with stress disorders. The model was a
      chronological one and included variables related to the women's premilitary
      experience, their military service, and their postmilitary experience. RESULTS:
      Altogether 48 percent of the sample served overseas, and 12 percent were exposed
      to enemy fire. A total of 63 percent reported experiences of physical sexual
      harassment during military service, and 43 percent reported rape or attempted
      rape. Both duty-related and sexual stress were found to contribute separately and
      significantly to the development of PTSD. Sexual stress was found to be almost
      four times as influential in the development of PTSD as duty-related stress.
      Postmilitary social support played a highly significant mediational role between
      sexual stress during military service and development of PTSD. CONCLUSIONS:
      Women's exposure to sexual stress in the military is much more prevalent than
      previously believed. It is particularly toxic for the development of PTSD.
      Correct assessment is essential to effective treatment.

PMID- 9603571
TI  - Mentally ill mothers who have killed: three cases addressing the issue of future
      parenting capability.
AB  - Many parents with severe and chronic mental illness lose custody of their
      children due to child abuse or neglect. These children may linger in foster care
      for long periods of time until decisions about custody are made. Recent proposals
      to shorten the time that children remain in the foster care system include the
      use of categories of abuse to guide decisions about custody. One proposal has
      been to "fast-track" cases involving parents with long-standing mental disorders
      by automatically terminating parental rights. This approach assumes that a severe
      and chronic mental disorder is incompatible with safe parenting. This report
      describes three cases of mentally ill mothers who lost custody of their children
      after they killed someone. The mothers were nonetheless found to be at low risk
      for future child maltreatment and violence according to evaluation with two
      current methodologies, Parenting Risk Assessment and Risk of Violence Assessment.
      The cases question the assumption that mental illness is incompatible with safe
      parenting and underscore the fact that evaluation of the parenting competency of
      mentally ill parents is rarely clear-cut.

PMID- 9603573
TI  - Age, ethnicity, and comorbidity in a national sample of hospitalized alcohol
      dependent women veterans.
AB  - OBJECTIVE: Treatment patterns in a national sample of hospitalized women veterans
      diagnosed with alcohol dependence were identified with the goal of improving
      health services to women veterans with alcohol-related disorders. METHODS:
      Information from VA's patient treatment file for fiscal year 1993 was used to
      identify 854 women veterans diagnosed with alcohol dependence. Of that group, 546
      received a primary diagnosis of alcohol dependence, and 308 received a secondary
      diagnosis of alcohol dependence after they sought treatment for other health
      problems. Chi square tests and multivariate logistic regression analyses were
      used to examine relationships between the sociodemographic profiles of these
      women and the types of services they received. RESULTS: The study population's
      largest age group (49 percent) was 30 to 39 years old. Fifty-two percent of the
      women were divorced or separated, and 62 percent were Caucasian. The overwhelming
      majority of comorbid diagnoses were of psychiatric disorders. Overall, only 47
      percent of the 854 patients received formal treatment for their alcohol disorder,
      and only 34 percent completed alcohol treatment. Women over age 60 were
      significantly less likely than women in other age groups to enter or complete
      formal treatment. Native-American women were significantly more likely than
      Caucasians or African Americans to receive formal alcohol treatment services.
      CONCLUSIONS: The results indicate a need for targeting interventions more
      effectively in certain groups of women veterans diagnosed with alcoholism. Low
      completion rates also suggest a need for greater incentives for patients to
      complete treatment programs.

PMID- 9603574
TI  - Use of dialectical behavior therapy in a partial hospital program for women with
      borderline personality disorder.
AB  - Dialectical behavior therapy, an outpatient psychosocial treatment for
      chronically suicidal women with borderline personality disorder, has been adapted
      for use in a partial hospital program for women. Patients attend the program for
      a minimum of five days of individual and group therapy, and full census is 12
      women. About 65 percent of participants meet at least three criteria for
      borderline personality disorder, and most have suicidal and self-injurious
      behavior. Their comorbid diagnoses include trauma-related diagnoses and anxiety
      disorders, severe eating disorders, substance abuse, and depression. The partial
      hospital program is linked to an aftercare program offering six months of
      outpatient skills training based on dialectical behavior therapy. Both programs
      focus on teaching patients four skills: mindfulness (attention to one's
      experience), interpersonal effectiveness, emotional regulation, and distress
      tolerance. Two years of operation of the women's partial hospital program
      provides promising anecdotal evidence that dialectical behavioral therapy, an
      outpatient approach, can be effectively modified for partial hospital settings
      and a more diverse population.

PMID- 9603575
TI  - A service for women with schizophrenia.
AB  - A program for women with schizophrenia that combines inpatient, outpatient, and
      outreach services is described. The program was established at the Clarke
      Institute of Psychiatry at the University of Toronto in 1995. Services include a
      comprehensive patient and family assessment, with subsequent recommendations to
      the treating clinician about differential diagnosis, psychopharmacologic and
      psychosocial treatments, and patient management during pregnancy and early
      parenthood. Other components of the program are home-based outreach services,
      substance abuse counseling, instruction of new mothers and parenting training,
      sex education, relationship-focused groups, and self-protection in an urban
      environment to prevent victimization. The clinic has established liaisons with
      pediatricians and gynecologists in the community to provide care to clinic
      patients. Linkages have also been established with agencies and facilities to
      fill gaps in the service spectrum, such as fitness programs and leisure
      activities and children's aid and protection.

PMID- 9603576
TI  - The effect of victimization on clinical outcomes of homeless persons with serious
      mental illness.
AB  - OBJECTIVE: The study examined the prevalence and correlates of criminal
      victimization and the relationship between victimization and client outcomes for
      homeless clients with mental illness. METHODS: Subjects were clients in community
      treatment programs participating in the Access to Community Care and Effective
      Services and Supports (ACCESS) program of the Center for Mental Health Services.
      Data were obtained through interviews conducted at program entry and at three and
      12 months after entry with ACCESS clients in 18 sites during the first year of
      program operation (N = 1,839). Self-reports of victimization during the past two
      months as well as data on sociodemographic, health, and social adjustment
      indicators were obtained at each time point. Multiple regression was used to
      determine both the correlates of victimization among this population and the
      effect of recent victimization on client outcomes three and 12 months after
      program entry. RESULTS: Forty-four percent of the clients were the victims of at
      least one crime during the two months before entering the program. Women were
      significantly more likely than men to have been victimized. Multivariate analysis
      showed that the more severe the client's psychotic symptoms, alcohol abuse, and
      criminal history, the more likely he or she was to have been victimized. Recent
      victimization had a significant impact on client outcomes in terms of increased
      homelessness and decreased quality of life. Victimization shortly before program
      entry was also the single most important predictor of victimization at both
      follow-up points. CONCLUSIONS: These findings suggest the critical need for
      service providers who work with homeless people with serious mental illness to
      assess the extent to which they have been victims of crime and to address issues
      of victimization and safety along with psychiatric and social adjustment
      problems.

PMID- 9603577
TI  - Sources of diagnostic uncertainty for chronically psychotic cocaine abusers.
AB  - OBJECTIVE: This study determined the sources and frequency of diagnostic
      uncertainty for patients with chronic psychosis and active cocaine abuse or
      dependence and assessed the usefulness of prospective follow-up in clarifying
      diagnosis. METHODS: A total of 165 male patients with chronic psychoses and
      cocaine abuse or dependence on inpatient units of a Veterans Affairs medical
      center were evaluated using the Structured Clinical Interview for DSM-III-R (SCID
      R), urine tests, hospital records, and interviews with collateral sources. An
      algorithm allowing key SCID-R items and diagnostic criteria to be designated as
      provisionally met or uncertain was applied, resulting in a provisional diagnosis
      and a list of alternate diagnoses. The assessment was repeated 18 months later in
      an attempt to resolve diagnostic uncertainty. RESULTS: In 30 cases (18 percent),
      initial assessment produced a definitive diagnosis, including 21 cases of
      schizophrenia, six of schizoaffective disorder, and three of psychostimulant
      induced psychotic disorder. In the other 135 cases, a definitive diagnosis could
      not be reached because of one or more sources of diagnostic uncertainty,
      including insufficient periods of abstinence (78 percent), poor memory (24
      percent), and inconsistent reporting (20 percent). Reassessment at 18 months led
      to definitive diagnoses in 12 additional cases. CONCLUSIONS: It was frequently
      difficult to distinguish schizophrenia from chronic substance-induced psychoses.
      Rather than concluding prematurely that psychotic symptoms are, or are not,
      substance induced, clinicians should initiate treatment of both psychosis and the
      substance use disorder in uncertain cases. The persistence or resolution of
      psychosis during abstinence and additional history from the stabilized patient or
      collateral sources may clarify the diagnosis.

PMID- 9603578
TI  - County funding of mental health services in a rural state.
AB  - Relationships between funding for mental illness in Iowa counties and county
      wealth, political activism, need for public services, rural culture, and policy
      makers' attitudes were examined. Counties with fewer people, lower proportions of
      persons with college education, higher proportions of rural and elderly
      residents, higher rates of poverty, and a higher proportion of income from farms
      spent less money on mental health services. Regression analysis indicated that
      the size of the county population and the proportion of persons receiving
      Medicaid funds explained 96 percent of the variation between county budgets.

PMID- 9603579
TI  - Depression screening scores during residential drug treatment and risk of drug
      use after discharge.
AB  - Depression is a highly prevalent disorder among patients in residential drug
      treatment, and the prognosis for recovery from chemical dependency among
      depressed persons is uncertain. This report presents one-year follow-up data on
      alcohol, cocaine, and marijuana use among patients who completed the Center for
      Epidemiologic Studies Depression Scale (CES-D) during their inpatient stay in one
      of 12 residential treatment programs in the Midwest. At 12-month follow-up, CES-D
      scores in the depressed range were significantly associated with risk of relapse
      for alcohol and marijuana use, but not for cocaine use.

PMID- 9603580
TI  - Preventive health care for mentally ill women.
AB  - Utilization of preventive medical care was compared for two low-income groups--47
      women with serious mental illness in an urban mental health center and 17 women
      patients at a primary care center. Appropriate preventive care was defined as at
      least one physical examination, a Pap test, and a breast examination in the past
      five years and a mammogram if the patient was over age 40. Receipt of preventive
      care by women in both settings was similar. Histories of physical and sexual
      abuse were prevalent in both groups, and a history of abuse was associated with
      less frequent receipt of preventive care. Results indicate that procedures to
      identify and provide services to women with abuse histories should be further
      developed.

PMID- 9603582
TI  - Recovered memories.

PMID- 9603581
TI  - Placebo in research on schizophrenia.

PMID- 9603583
TI  - Unworkable guidelines.

PMID- 9603584
TI  - Cytokines--the compounds of the nineties: where is it leading?

PMID- 9603585
TI  - Carbon dioxide and apnea: common knowledge and common sense.

PMID- 9603586
TI  - Interleukin-10 production during and after upper abdominal surgery.
AB  - STUDY OBJECTIVE: To evaluate the influence of major abdominal surgery on the
      plasma levels of interleukin-10 (IL-10). DESIGN: Prospective study. SETTING:
      University hospital. PATIENTS: 10 ASA physical status I and II patients
      undergoing upper abdominal surgery. INTERVENTIONS: All patients received combined
      general-epidural anesthesia with isoflurane and nitrous oxide, after insertion of
      an epidural catheter at T8-T9 dosed with 1.5% lidocaine. MEASUREMENTS AND MAIN
      RESULTS: Plasma interleukin-6 (IL-6), interleukin-8 (IL-8), and IL-10 levels were
      determined with an enzyme-linked immunosorbent assay at preanesthesia, 0, 2, and
      4 hours during surgery, and at the end of surgery, followed by sampling on the
      morning of postoperative days 1 (POD1) and 3 (POD3). Before anesthesia and at 0
      hours of surgery, IL-10 was not detected. In all ten patients, the plasma levels
      of IL-10 showed significant elevations and achieved their maximal value 4 hours
      after the skin incision (p < 0.05 vs. baseline). The plasma IL-10 levels returned
      to preanesthesia levels on POD3. The plasma levels of IL-6 and IL-8 also
      increased in the perioperative period. The peak cytokine levels correlated (r =
      0. 915, p = 0.0001 for IL-6 vs. IL-8; r = 0.82, p = 0.025 for IL-6 vs. IL-10; and
      r = 0.641, p = 0.06 for IL-8 vs. IL-10). The peak plasma IL-10 levels
      significantly correlated with the amount of intraoperative blood loss (r = 0.69,
      p < 0.05). CONCLUSIONS: In patients undergoing major abdominal surgery, plasma IL
      10 levels were elevated during and after operation. IL-10 may modulate the
      inflammatory responses in the perioperative period.

PMID- 9603587
TI  - Carbon dioxide dynamics during apneic oxygenation: the effects of preceding
      hypocapnia.
AB  - STUDY OBJECTIVE: To compare the rate of increase of arterial carbon dioxide
      tension (PaCO2) during apneic oxygenation preceded by acute respiratory
      hypocapnia with that during apnea preceded by respiratory eucapnia. DESIGN:
      Randomized, prospective, single crossover study. SETTING: Operating room at a
      teaching hospital. PATIENTS: 19 ASA physical status I, II, and III patients
      requiring general endotracheal anesthesia and invasive monitoring for elective
      surgery. INTERVENTIONS: Two ventilatory states preceding apneic oxygenation were
      studied in each patient. The first respiratory state was established using
      controlled mechanical ventilation in the stable, anesthetized patient, followed
      by a 5-minute period of apneic oxygenation. Arterial and mixed central venous
      blood gas samples were obtained simultaneously prior to and at 1-minute intervals
      during apnea. Ventilatory parameters were then changed to establish the second
      respiratory state. During the subsequent period of apnea, the study was repeated
      as above. MEASUREMENTS AND MAIN RESULTS: Arterial and mixed central venous
      partial pressure of carbon dioxide (pCO2) levels were measured. A greater
      increase in PaCO2 was found during the first minute of apneic oxygenation in the
      hypocapneic group compared with the eucapneic group. The venoarterial gradient of
      pCO2 was also greater in the hypocapneic group prior to apnea. CONCLUSIONS: Acute
      hypocapnia compared with eucapnia prior to apneic oxygenation is associated with
      a greater rise in PaCO2 in the anesthetized patient. This finding may be due in
      part to widening of the venoarterial gradient of pCO2.

PMID- 9603588
TI  - Effects of cisatracurium in children during halothane-nitrous oxide anesthesia.
AB  - STUDY OBJECTIVE: To determine the neuromuscular blocking effect and recovery
      profile of cisatracurium besylate in children after administration of a bolus
      dose that was twice the estimated dose required to produce 95% of the maximum
      effect (2 x ED95; 0.08 mg/kg) followed by an infusion during halothane-nitrous
      oxide anesthesia. STUDY DESIGN: Open-label study. SETTING: Teaching hospital.
      PATIENTS: 30 male and female (ASA physical status I and II) patients, 2 to 10
      years of age, scheduled for elective surgery of low to moderate risk.
      INTERVENTIONS: After induction of general anesthesia, patients received
      cisatracurium 0.08 mg/kg administered over 5 to 10 seconds. For surgical
      procedures requiring neuromuscular block for at least 60 minutes, a second bolus
      dose of cisatracurium 0.02 mg/kg was administered after the first response to a
      train-of-four stimuli (T1) recovered to 25% of baseline. When T1 was 5% of
      baseline after the second dose, a 3 microg/kg/min infusion of cisatracurium was
      initiated and titrated to maintain 89% to 99% block for the duration of the
      surgery. For procedures requiring neuromuscular block of less than 60 minutes,
      one or more maintenance doses of 0.02 mg/kg cisatracurium were administered when
      T1 was 25% of baseline after the preceding dose. In 10 patients, recovery was
      facilitated with edrophonium 1.0 mg/kg administered when T1 was 26% to 48% of the
      final baseline. MEASUREMENTS AND MAIN RESULTS: Evoked muscular response at the
      adductor pollicis was measured by electromyography. With 0.08 mg/kg, onset time
      (mean +/- SEM) was 4.1 +/- 0.4 minutes, and clinically effective duration was
      27.3 +/- 0.9 minutes. Mean 5% to 95% and 25% to 75% recovery indices were 28.4 +/
      2. 7 minutes and 11.2 +/- 0.8 minutes, respectively. The mean infusion rate
      necessary to maintain 89% to 99% T1 suppression for 17 to 145 minutes was 1.7
      microg/kg/min. After termination of infusion, the mean 5% to 95% and 25% to 75%
      recovery indices were similar to those after a single bolus dose, and time to 95%
      recovery was 30.4 +/- 3.0 minutes. After administration of edrophonium, full
      recovery (T4:T1 > or = 70%) occurred in 1.5 +/- 0.4 minutes. No clinically
      significant changes in heart rate or blood pressure were noted during the first 5
      minutes after administration of cisatracurium 0.08 mg/kg. CONCLUSIONS:
      Cisatracurium provided maximal neuromuscular block, cardiovascular stability, and
      predictable recovery at the doses tested. In view of this finding, cisatracurium
      should be a useful intermediate-duration neuromuscular blocking drug for children
      during general anesthesia.

PMID- 9603589
TI  - Comparison of acceleromyography and electromyography in vecuronium-induced
      neuromuscular blockade with xenon or sevoflurane anesthesia.
AB  - STUDY OBJECTIVES: To compare acceleromyography (AMG) and electromyography (EMG)
      with xenon or sevoflurane anesthesia during vecuronium-induced neuromuscular
      blockade. DESIGN: Prospective randomized study. SETTING: University hospital.
      PATIENTS: 28 ASA physical status I and II adult patients presenting for elective
      surgery. INTERVENTIONS: Patients received vecuronium for neuromuscular blockade
      and either xenon (n = 11) or sevoflurane (n = 17) anesthesia. MEASUREMENTS AND
      MAIN RESULTS: The first twitch depression, which was expressed as a ratio of the
      first twitch to that obtained before the blocking drug was administered (T1/Tc),
      was measured simultaneously by AMG and EMG. T1/Tc as measured by AMG consistently
      demonstrated greater depression than that by EMG during recovery. The limits of
      agreement were unacceptably wide, suggesting that T1/Tc obtained by AMG is a poor
      predictor of T1/Tc as measured by EMG. Such relations were not affected by the
      anesthetic (xenon or sevoflurane) used. CONCLUSION: AMG and EMG-cannot be used
      interchangeably with either xenon or sevoflurane anesthesia.

PMID- 9603590
TI  - Evaluation of anxiolysis and pain associated with combined peri- and retrobulbar
      eye block for cataract surgery.
AB  - STUDY OBJECTIVES: To evaluate five different preoperative anxiolytic regimens in
      cataract surgery performed under regional anesthesia; to quantify the pain
      associated with combined peri- and retrobulbar injection (PRBI) of local
      anesthetic drugs; and to describe a technique of painless eye block. DESIGN:
      Randomized, double blind, placebo-controlled study. SETTING: Private clinic.
      PATIENTS: 376 ASA I and II patients presenting for cataract surgery.
      INTERVENTIONS: Patients were extensively briefed by the nursing staff on the
      various procedures. Of the 376 study patients, 136 preferred to have no
      anxiolytic drug. The remaining 240 patients were randomly allocated to one of six
      groups to receive either 3 mg of bromazepam, 6 mg of bromazepam, 0.5 mg of
      alprazolam, 1 mg of alprazolam, 5 mg of diazepam, or a placebo on a double-blind
      protocol. All patients received a standard combined peri- and retrobulbar eye
      block (PRBB) before surgery. MEASUREMENTS AND MAIN RESULTS: Anxiety at various
      stages of the procedure and PRBB were measured on visual analog scale (0-10).
      PRBB pain was compared with pain of intravenous (i.v.) cannula placement. On
      admission, anxiety of the 136 patients who preferred no anxiolytic premedication
      was significantly less than that of the 240 patients assigned to one of the six
      treatment groups (p < 0.05). There was no difference between the six treatment
      groups in reported anxiety before surgery (p > 0.05) except for Group 1 (3 mg
      bromazepam), where anxiety increased before and during PRBB administration (p <
      0.05). In all six treatment groups, anxiety decreased significantly 30 minutes
      after medication was administered (p < 0.05). For the total group, 61.18% of
      patients reported more or equal pain associated with the placement of the 20
      gauge i.v. cannula than by the PRBB. Of the patients who received medication, 94%
      stated that, should they require another eye operation, they would like the same
      anxiolytic treatment. No patient requested general anesthesia for their next
      operation or to be rendered unconscious for PRBB. CONCLUSIONS: 1. There was
      interpersonal variation in the level of preoperative anxiety. 2. In patients who
      were anxious, the anxiolytic drugs and placebo decreasedanxiety although the
      level of anxiety did not differ between the anxiolytic drugs or between placebo
      and the anxiolytic drugs. The only difference was in Group 1 patients (3 mg
      promazepam), who reported slightly increased anxiety before and during PRBB
      administration (p < 0.05). 3. Placement of the PRBB is less painful than the
      insertion of a 20 g i.v. cannula.

PMID- 9603591
TI  - Ondansetron in the prophylaxis of postoperative vomiting: a meta-analysis.
AB  - STUDY OBJECTIVES: To assess the efficacy of ondansetron and the incidence of
      headache when used as prophylaxis for postoperative vomiting. DATA SOURCES:
      Studies were identified using MEDLINE (January 1990 to July 1997) with the key
      words: "vomiting," "ondansetron," and "surgery" and/or "anesthesia." STUDY
      SELECTION: All prospectively randomized trials in which ondansetron and placebo
      had been administered for prevention of postoperative vomiting. DATA EXTRACTION:
      Data on patient numbers, gender and ages, drug dosage, outcomes (incidence of
      vomiting and incidence of headache), time of outcome (up to 8 hrs or up to 48 hrs
      postoperatively), and baseline risk for vomiting according to type of surgical
      intervention were extracted. MAIN RESULTS: 48 trials involving 12,078 patients
      (10,390 adults and 1688 children) met the selection criteria. No evidence was
      found that the drug became more effective at doses larger than 4 mg. The dose of
      8 mg was not statistically demonstrated to be superior (p = 0.558), while that of
      1 mg was barely effective. The meta-analysis indicated that when the incidence of
      vomiting is elevated (e.g., the combined average of the placebo groups of 48%),
      on the statistical (i.e., hypothetical) grounds of six patients being treated
      with 4 mg of ondansetron, one will not vomit due to the treatment and, of the
      rest, two patients would have vomited despite the treatment and three patients
      would not have vomited anyway. The overall incidence of headache was 7.05% in
      ondansetron groups versus 6.16% in placebo groups. CONCLUSIONS: While ondansetron
      is an effective antiemetic with minimal adverse effects, the data obtained on the
      numbers needed to be treated calculation for prophylaxis of postoperative
      vomiting should be considered in future cost-effective strategies of
      postoperative management.

PMID- 9603592
TI  - Effect of controlled hypotension combined with hemodilution on gastric intramural
      pH.
AB  - STUDY OBJECTIVE: To evaluate the effect of controlled hypotension combined with
      hemodilution on gastric intramural pH in the clinical setting. DESIGN:
      Randomized, prospective study. SETTING: Inpatient surgery at Nagasaki Rosai
      Hospital. PATIENTS: 30 ASA physical status I and II patients scheduled for total
      hip arthroplasty. INTERVENTIONS: Patients were randomly divided into two groups.
      Group A (n = 15) received controlled hypotension with mild hemodilution. Group B
      (n = 15) received controlled hypotension with moderate hemodilution. Hemodilution
      was carried out after induction of anesthesia. Drawn blood was replaced with 6%
      hydroxyethyl starch solution. Final hematocrit values were 32 +/- 2% (mean +/-
      SD) in Group A and 23 +/- 2% in Group B. Controlled hypotension was induced with
      prostaglandin E1 (PGE1) to maintain mean arterial blood pressure at 55 mmHg for
      80 minutes. MEASUREMENTS AND MAIN RESULTS: Measurements included gastric
      intramural pH (pHi), arterial blood pH (pHa), and plasma lactate. These indices
      were measured before hemodilution, after hemodilution, 80 minutes after starting
      hypotension, 60 minutes after recovery from hypotension, and on the first
      postoperative day. The value of pHi was measured by tonometry. The pHa and
      lactate values showed no change in either Group A or Group B throughout the time
      course. Gastric pHi values showed no change in Group A throughout the time
      course. The pHi value in Group B showed a significant decrease from 7.420 +/-
      0.028 to 7.339 +/- 0.034 (p < 0.05) after hemodilution, while it showed no
      further decrease at 80 minutes after starting hypotension (7.331 +/- 0.039) and
      60 minutes after recovery from hypotension (7.330 +/- 0.048). CONCLUSION: The
      results suggest that moderate hemodilution, such as 23% of hematocrit value,
      might impair oxygenation in gastrointestinal mucosa, whereas controlled
      hypotension induced by PGE1 combined with the hemodilution would not increase
      this impairment.

PMID- 9603594
TI  - Considerations in placement of right internal jugular cannulas.
AB  - This case report describes a patient who had paroxysmal ventricular bigeminy of
      an unrecognized etiology. After 24 hours of observation, it was noted that the
      patient's head position correlated with the bigeminy. A single-lumen infusion
      catheter, which had been placed through an internal jugular cannula, was
      transduced and demonstrated a ventricular pressure waveform. This catheter was
      removed and the ectopy resolved. The factors associated with this arrhythmia are
      discussed.

PMID- 9603593
TI  - Anesthetic management of a patient with myasthenia gravis during hypothermic
      cardiopulmonary bypass.
AB  - The anesthetic management of a patient with myasthenia gravis (MG) who underwent
      cardiac surgery with hypothermic cardiopulmonary bypass (CPB) is described. Using
      total intravenous anesthesia with propofol and a moderate dose fentanyl, the
      variations of neuromuscular function and serum anti-acetylcholine receptor
      antibody concentration were examined in relation to hypothermic CPB in the
      absence of muscle relaxants. The anesthetic technique used may have helped to
      avoid the risks incidental to muscle relaxants in this patient with MG undergoing
      hypothermic CPB.

PMID- 9603595
TI  - Difficult intubation from gastroesophageal reflux disease in adults.
AB  - Two cases of difficult intubation are presented. Both cases presented with red
      swollen arytenoids, swollen false vocal cords, and subglottic stenosis. Tracheal
      intubation could not be achieved for these reasons. Both patients were placed on
      gastrointestinal prokinetic drugs and histamine-two blocker, as a diagnosis of
      gastroesophageal reflux disease (GERD) was made. In one case, follow-up by an
      otolaryngotic surgeon showed reversal of the above findings. In the other case,
      one tracheal intubation was achieved eventually. GERD occurs frequently.
      Clinicians need to maintain a high index of suspicion for GERD-related airway
      changes so as to avoid potential difficult intubations.

PMID- 9603596
TI  - Large pulmonary embolus without systemic hemodynamic consequences during cemented
      hip arthroplasty.
AB  - A case is presented in which a large embolus was detected passing through the
      right side of the heart during total hip arthroplasty. Although tricuspid
      regurgitation and an elevated right ventricular pressure resulted, there was no
      perturbation in systemic hemodynamics or gas exchange. The emboli detected during
      total hip arthroplasty are most likely composed of fat. No specific treatment is
      required, although heightened vigilance for disturbances in systemic hemodynamics
      is important.

PMID- 9603598
TI  - Sympathetically mediated pain after reduction mammoplasty: an unusual
      complication.
AB  - We present a case report of a patient who developed an unusual bilateral breast
      pain syndrome after a reduction mammoplasty. Her symptoms and physical
      examination findings resolved after four stellate ganglion blocks, of which two
      on each side were performed over a period of 2 weeks. The case serves to alert
      clinicians to the possibility of a patient developing a sympathetically mediated
      pain syndrome after reduction mammoplasty.

PMID- 9603597
TI  - Propofol anesthesia for cesarean section successfully managed in a patient with
      moyamoya disease.
AB  - We report a case of general anesthesia in a 25 year-old female patient with
      moyamoya disease who presented for cesarean section. General anesthesia was
      induced with propofol 100 mg, succinylcholine 50 mg, and nicardipine 1 mg
      intravenously (i.v.), and maintained with 60% nitrous oxide in oxygen. Just after
      the clamp of the umbilical cord, propofol 10 mg/kg/hr following propofol 50 mg
      pentazocine 15 mg vecuronium 8 mg, and methylergometrine maleate 0.2 mg were
      given i.v. The rate of infusion of propofol was reduced to 8 mg/kg/hr 10 minutes
      after the clamp and reduced to 6 mg/kg/hr 20 minutes after the clamp. Additional
      pentazocine 15 mg was given i.v. Blood pressure was maintained between 110 and
      145 systolic, and 50 and 85 diastolic mmHg, and end-tidal carbon dioxide was
      between 34 and 36 mmHg. No postoperative deterioration of the patient's
      neurologic findings occurred. For the anesthetic management of moyamoya disease
      patients, especially in delivery, it is important to avoid hemodynamic changes
      and to maintain cerebral blood flow (CBF). We used propofol for hemodynamic
      stability and avoided hyperventilation so as to maintain CBF. We successfully
      managed the patient perioperatively.

PMID- 9603599
TI  - Early extubation and neurologic examination following combined carotid
      endarterectomy and coronary artery bypass grafting using remifentanil.
AB  - Carotid endarterectomy (CEA) and coronary artery bypass grafting (CABG) as a
      combined procedure is occurring with increasing frequency. CEA-CABG incurs the
      morbidity of both procedures, and considerations for this procedure include
      anesthetic techniques that provide hemodynamic stability and prompt emergence
      from anesthesia. We present, to our knowledge, the first reported use in a
      combined CEA-CABG of the novel opioid remifentanil as a component of the
      anesthetic technique to achieve these goals. Remifentanil allows for early
      neurologic evaluation without sacrificing the hemodynamic stability of
      traditional, high-dose opioid techniques.

PMID- 9603600
TI  - Aortic stenosis with end-stage liver disease: prioritizing surgical and
      anesthetic therapies.
AB  - A 48-year-old man with end-stage liver disease and aortic stenosis (AS), was
      being evaluated for liver transplantation. This report focuses on the question of
      which medical problem to correct first, the end-stage liver disease or the AS.
      Risk factors for surgical correction of AS and liver transplantation are reviewed
      and discussed, and the surgical and anesthetic management strategies for this
      patient are outlined.

PMID- 9603601
TI  - Patient safety and scented pediatric anesthesia facemasks.

PMID- 9603602
TI  - Patient safety and scented pediatric anesthesia facemasks.

PMID- 9603603
TI  - Lighted stylet as an aid to blind tracheal intubation via the LMA.

PMID- 9603604
TI  - Bags of air.

PMID- 9603605
TI  - Coronary artery aneurysm complicating a coronary artery fistula: management by
      transesophageal echocardiography.

PMID- 9603606
TI  - Genome-wide search for genes affecting the risk for alcohol dependence.
AB  - Alcohol dependence is a leading cause of morbidity and premature death. Several
      lines of evidence suggest a substantial genetic component to the risk for
      alcoholism: sibs of alcoholic probands have a 3-8 fold increased risk of also
      developing alcoholism, and twin heritability estimates of 50-60% are reported by
      contemporary studies of twins. We report on the results of a six-center
      collaborative study to identify susceptibility loci for alcohol dependence. A
      genome-wide screen examined 291 markers in 987 individuals from 105 families. Two
      point and multipoint nonparametric linkage analyses were performed to detect
      susceptibility loci for alcohol dependence. Multipoint methods provided the
      strongest suggestions of linkage with susceptibility loci for alcohol dependence
      on chromosomes 1 and 7, and more modest evidence for a locus on chromosome 2. In
      addition, there was suggestive evidence for a protective locus on chromosome 4
      near the alcohol dehydrogenase genes, for which protective effects have been
      reported in Asian populations.

PMID- 9603607
TI  - Evidence for genetic linkage to alcohol dependence on chromosomes 4 and 11 from
      an autosome-wide scan in an American Indian population.
AB  - To identify specific genes affecting vulnerability or resistance, we performed a
      whole-autosomal genome scan for genetic linkage to alcohol dependence in a
      Southwestern American Indian tribe. Genotypes at 517 autosomal microsatellite
      loci and clinical evaluations were available for 152 subjects belonging to
      extended pedigrees and forming 172 sib-pairs. Highly suggestive evidence for
      linkage emerged for two genomic regions using two- and multipoint sib-pair
      regression methods; both regions harbored neurogenetic candidate genes. The best
      evidence is seen with D11S1984 (nominal P = 0.00007, lod approximately equal to
      3.1) on chromosome 11p, in close proximity to the DRD4 dopamine receptor and
      tyrosine hydroxylase (TH) genes. Good evidence is seen with D4S3242 (nominal P =
      0.0002, lod approximately equal to 2.8) on chromosome 4p, near the beta1 GABA
      receptor gene. Interestingly, three loci in the alcohol dehydrogenase gene
      cluster on chromosome 4q showed evidence for linkage with two-point analyses, but
      not multipoint analysis.

PMID- 9603608
TI  - Clinical description of an adult male with psychosis who showed FMR1 gene
      methylation mosaicism.
AB  - Unstable trinucleotide repeat DNA contained in numerous genes has been proposed
      as the underlying mechanism in the clinical phenomenon of genetic anticipation in
      fragile X syndrome and other neurodegenerative diseases. No clear evidence has
      been found for the role of these abnormal trinucleotide repeat expansion
      containing genes in schizophrenia or other psychiatric disorders. This report
      describes an adult male with psychosis who was later found to have methylation
      mosaicism of the FMR1 gene. We discuss history, examination, and investigation
      which led to the diagnosis and treatment response of this patient.

PMID- 9603609
TI  - Analysis of a novel functional polymorphism within the promoter region of the
      serotonin transporter gene (5-HTT) in Brazilian patients affected by bipolar
      disorder and schizophrenia.
AB  - It has been suggested that the serotonin transporter (5-hydroxytryptamine
      transporter or 5-HTT) may be involved in the pathogenesis of affective disorders.
      Recently, Collier et al. (1996) found that the frequency of the low-activity
      short variant (s) of the 5-HTT-linked polymorphic region (5-HTTLPR) was higher
      among patients with affective disorders than in normal controls. However, since
      the observed level of significance was not high, they suggest that these findings
      should be replicated in independent samples. We have analyzed 86 unrelated
      patients (47 with bipolar disorder and 39 with schizophrenia) and 98 normal
      controls from the Brazilian population for the 5-HTTLPR. Statistical analysis
      revealed that the genotypes (LL, Ls, ss) as well as the estimated allele
      frequencies (L,s) did not differ significantly among the three studied groups or
      between bipolar and normal controls. In addition, although not statistically
      significant, the genotype ss in our sample was less frequent among our bipolar
      patients than in our normal controls (12.8% versus 16.3%) which is the opposite
      of what was found by Collier et al. (24% versus 18%) in the European study.
      Although it will be important to extend the present analysis in a larger sample,
      our preliminary results suggest that the 5-HTTLPR does not seem to play a major
      role in the genetics of bipolar and schizophrenic disorders at least in this
      group of Brazilian psychiatric patients.

PMID- 9603610
TI  - Possible association of a cholecystokinin promotor polymorphism (CCK-36CT) with
      panic disorder.
AB  - We searched for mutations in the CCK gene in panic disorder with single-strand
      conformational polymorphism (SSCP) analysis of the three exons and promotor
      region of the gene. We found a C-->T transition at position -36 (CCK(-36C-->T))
      in a GC box, a binding site for transcription factor Sp1, in the promotor region.
      The allele frequency was 0.168 (95% CI, 0.116-0.221) in 98 persons with panic
      disorder and 0.083 (95% CI, 0.059-0.107) in 247 geographically matched,
      unscreened controls. A transmission disequilibrium test based on panic disorder
      as the affected phenotype was nonsignificant (chi2 = 0.93), but when panic
      disorder or attacks were considered as affected, statistically significant
      transmission disequilibrium was detected (chi2 = 4.00, P < 0.05). Linkage
      analysis was uninformative. In exploratory analyses to search for clinical
      correlations, the "T" allele was found in 59% of 22 persons with panic attacks
      but not panic disorder, compared with 31% of those who met the criteria for panic
      disorder. An association between the CCK polymorphism and panic disorder cannot
      be considered established due to the inconsistencies in the results noted above,
      but if the provisional association can be replicated, the findings are consistent
      with CCK(-36C-->T) being a disease-susceptibility allele that alone is neither
      necessary nor sufficient to cause panic disorder but that increases vulnerability
      by acting epistatically.

PMID- 9603611
TI  - Behavioral phenotypes: conceptual and methodological issues.
AB  - Specific behavioral patterns associated with chromosomal and genetic disorders
      are being recognized more frequently. The hope is that the demonstration of a
      behavioral phenotype with a particular syndrome may lead to the isolation of the
      behavior's genetic determinants. Three issues are considered here: the problem of
      defining a behavioral phenotype, the difficulty of demonstrating the existence of
      a behavioral phenotype, and the likelihood of characterizing etiologically
      important genes. Although there are many impediments to success, the value of
      recognizing behavioral phenotypes within a diagnostic syndrome is emphasized, and
      examples are given of how this may lead to isolating behavioral genes.

PMID- 9603612
TI  - Mutation screening of the dopamine D1 receptor gene in Tourette's syndrome and
      alcohol dependent patients.
AB  - We report a single stranded conformational polymorphism (SSCP) analysis of the
      coding region of the dopamine D1 receptor (DRD1) in Tourette's syndrome (n = 50)
      and control (n = 50) subjects. Tourette's syndrome populations with comorbidity
      for attention deficit-hyperactivity disorder (AD-HD) (n = 35) and obsessive
      compulsive disorder (OCD) (n = 30) were also screened. As a related study, we
      also screened patients diagnosed with alcohol dependence (n = 72). The present
      study discovered no DRD1 coding region mutations in any of the Tourette's
      syndrome or alcohol dependent patients. One silent mutation, a C for a T at
      Ile49, was discovered in one control subject. The non-polymorphic structure of
      the DRD1 gene among the Tourette's syndrome, Tourette's syndrome comorbid with AD
      HD and OCD and the alcohol dependent populations screened by SSCP suggests that
      coding region mutations of the DRD1 gene are unlikely to contribute to the
      inheritance of these disorders.

PMID- 9603613
TI  - No association of the tryptophan hydroxylase gene with bipolar affective
      disorder, unipolar affective disorder, or suicidal behaviour in major affective
      disorder.
AB  - Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of 5
      hydroxytryptamine (5-HT). An association study in bipolar affective disorder I or
      unipolar major affective disorder was performed by using a Bfa I restriction site
      polymorphism within intron 7 of the tryptophan hydroxylase gene. A total of 118
      bipolar, 125 unipolar, and 437 control subjects were used in the study (1:3.7
      bipolar:control, 1:3.5 unipolar:control). There were no significant differences
      in TPH allele or genotype frequencies between the affective disorder and control
      groups. In addition, bipolar and/or unipolar subjects with or without a history
      of suicide attempts were compared for the TPH polymorphism. No significant
      differences were found between suicidal and non-suicidal groups in major
      affective disorder, in contrast to a previous study suggesting an association of
      this polymorphism with a history of suicide attempts among alcoholic violent
      offenders.

PMID- 9603614
TI  - Integrating clinical and laboratory data in genetic studies of complex
      phenotypes: a network-based data management system.
AB  - The identification of genes underlying a complex phenotype can be a massive
      undertaking, and may require a much larger sample size than thought previously.
      The integration of such large volumes of clinical and laboratory data has become
      a major challenge. In this paper we describe a network-based data management
      system designed to address this challenge. Our system offers several advantages.
      Since the system uses commercial software, it obviates the acquisition,
      installation, and debugging of privately-available software, and is fully
      compatible with Windows and other commercial software. The system uses relational
      database architecture, which offers exceptional flexibility, facilitates complex
      data queries, and expedites extensive data quality control. The system is
      particularly designed to integrate clinical and laboratory data efficiently,
      producing summary reports, pedigrees, and exported files containing both
      phenotype and genotype data in a virtually unlimited range of formats. We
      describe a comprehensive system that manages clinical, DNA, cell line, and
      genotype data, but since the system is modular, researchers can set up only those
      elements which they need immediately, expanding later as needed.

PMID- 9603615
TI  - D2 and D4 dopamine receptor polymorphisms and personality.
AB  - The relationship of various dimensions of temperament, measured by the
      Tridimensional Personality Questionnaire (TPQ), to polymorphisms of the D2
      dopamine receptor (DRD2) and D4 dopamine receptor (DRD4) genes was determined in
      119 healthy Caucasian boys who had not yet begun to consume alcohol and other
      drugs of abuse. Total Novelty Seeking score of the TPQ was significantly higher
      in boys having, in common, all three minor (A1, B1, and Intron 6 1) alleles of
      the DRD2 compared to boys without any of these alleles. Boys with the DRD4 7
      repeat (7R) allele also had a significantly higher Novelty Seeking score than
      those without this allele. However, the greatest difference in Novelty Seeking
      score was found when boys having all three minor DRD2 alleles and the DRD4 7R
      allele were contrasted to those without any of these alleles. Neither the DRD2
      nor the DRD4 polymorphisms differentiated total Harm Avoidance score. Whereas
      subjects having all three minor DRD2 alleles had a significantly higher Reward
      Dependence 2 (Persistence) score than subjects without any of these alleles, no
      significant difference in this personality score was found between subjects with
      and without the DRD4 7R allele. In conclusion, DRD2 and DRD4 polymorphisms
      individually associate with Novelty Seeking behavior. However, the combined DRD2
      and DRD4 polymorphisms contribute more markedly to this behavior than when these
      two gene polymorphisms are individually considered.

PMID- 9603616
TI  - Nonparametric linkage does not provide strong evidence for linkage to APOE in a
      large Alzheimer's kindred.

PMID- 9603617
TI  - On cognitive variability in velocardiofacial syndrome: profound mental
      retardation and autism.

PMID- 9603618
TI  - Modeling NMR chemical shifts: a comparison of charge models for solid state
      effects on 15N chemical shift tensors.
AB  - This paper presents results from applying different point charge models to take
      into account intermolecular interactions to model the solid state effects on the
      15N NMR chemical shifts tensors. The DFT approach with the BLYP gradient
      corrected exchange correlation functional has been used because it can include
      electron correlation effects at a reasonable cost and is able to reproduce 15N
      NMR chemical shifts with reasonable accuracy. The results obtained with the point
      charge models are compared with the experimental data and with results obtained
      using the cluster model, which includes explicitly neighboring molecular
      fragments. The results show that the point charge models can take into account
      solid state effects at a cost much lower than the cluster methods.

PMID- 9603620
TI  - Wide frequency range 31P relaxation in the ion conducting glass LiPO3.
AB  - Spin-lattice relaxation studies on the stationary 31P nucleus have been performed
      in order to investigate to which extent the dynamics of the mobile lithium ions
      are reflected in the behavior of the glassy network. The temperature dependence
      of the 31P relaxation, which is governed by the heteronuclear dipole-dipole
      interaction between lithium and phosphorus, can be described in terms of a
      Gaussian distribution of activation energies and that over a wide frequency range
      from about 34 kHz to 81 MHz. A relaxation rate maximum, which provides useful
      information about correlation times and activation energies of the lithium-ion
      diffusion process, could only be observed in the rotating frame relaxation
      measurements.

PMID- 9603619
TI  - Kinetics of 1H --> 31P cross-polarization in human trabecular bone.
AB  - Bloch-decay and cross-polarization (CP) 31P nuclear magnetic resonance (NMR)
      spectra of healthy human trabecular bone were acquired under magic-angle spinning
      (MAS) at 3 kHz. A single peak at 3.1 ppm was detected. Variable-contact time 1H -
      > 31P CP experiments revealed three signal components growing at various rates.
      The fast, moderate and slow components were assigned and assessed in P atom % to
      proton-rich (24%), hydroxyapatite (58%) and proton-deficient (18%) phosphate
      domains, respectively. Examination of CP kinetics is useful for the chemical
      characterization of bone tissue.

PMID- 9603621
TI  - Potassium tetracyanoplatinate (II) trihydrate (K2Pt(CN)4 x 3H2O) studied by high
      resolution solid state 13C MAS NMR.
AB  - Prudent analysis of the solid state 13C MAS NMR spectra of polycrystalline
      K2Pt(CN)4 x 3H2O (KTCP)- reveals that in crystals of this compound there are two
      types of carbon nuclei with slightly different 13C chemical shift tensors,
      contrary to what is found for the solution NMR spectrum and previous static
      powder NMR studies on this compound and the high resolution solid state NMR
      studies on other similar compounds. The 13C MAS spectra measured at different
      rotor spinning speeds are satisfactorily simulated though the use of a newly
      developed computer program based on a novel density matrix formulation. The
      present method is eminently successful even though the spectra are rather
      complicated because of (1) the relatively large anisotropies of the chemical
      shift tensors; (2) the high-order dipolar interactions between 13C and 14N nuclei
      because of the strong quadrupolar coupling constants of 14N nuclei; and (3) the
      indirect J-coupling between the 13C and 195Pt. The principal elements as well as
      their orientations of the two 13C chemical shift tensors are evaluated from the
      spectral simulations.

PMID- 9603622
TI  - Triple, quintuple and higher order multiple quantum MAS NMR of quadrupolar
      nuclei.
AB  - The optimization of the coherence transfers involved in five, seven and nine
      quantum versions of the recently discovered MQMAS technique, is analysed
      numerically. Data reported in this paper may serve as starting parameters for the
      experiment set up. An analysis of the intensity and resolution given by each type
      of experiment is performed, which confirms the need to use very high rf fields
      for MQ transfers. It follows that five-quantum is achievable rather easily but
      the use of seven and nine-quantum MAS experiments becomes increasingly difficult
      due to the demand for high rf power and decreasing sensitivity. The advantages of
      using the z-filter MQMAS method with respect to a two-pulse sequence are
      analysed. The method for qualitatively and quantitatively interpret the MQMAS
      spectra is described. The nature of the spinning side bands along the multiple
      quantum dimension is explained. It is shown that the rotor synchronization can be
      conveniently used to eliminate these side bands, but only for 3QMAS experiments.
      The use of the multiple-quantum method in combination with static samples and
      VAS, DAS and DOR techniques is finally discussed.

PMID- 9603623
TI  - Study of fast switching processes due to electric and magnetic fields--an NMR
      approach.
AB  - Solid state NMR techniques have been developed to investigate dynamic molecular
      effects (e.g., molecular reorientations) due to simultaneously applied external
      electric fields on electrically sensitive materials such as liquid crystals (LC),
      liquid crystalline polymers (LCP) and polymeric electrets. Such effects can be
      observed only on relatively thin systems (10-200 microm). That means that many
      scans are necessary to achieve a sufficiently high signal-to-noise-ratio in the
      spectra (500-1000 scans). If the material is also magnetically sensitive, the
      electric field can be used to orient molecules in a starting orientational state
      and by switching-off the voltage to access fast reorientation processes in the
      magnetic field B0. Until now, the behaviour of orientable molecular systems under
      the influence of electric fields has been investigated by means of a more or less
      quasistatic approach (LCP: 100 V, electrets: 1 kV) in equilibrium states. The
      achievable time resolution depends on the desired signal-to-noise-ratio. For the
      case of proton NMR this means a time resolution of about 10 min. However, very
      often switching processes occur on a much shorter time scale. Using conventional
      techniques it is impossible to observe fast (ca. 100 micros) electrically or
      magnetically induced reorientation processes. In this work, we present a concept
      to overcome the problems outlined above and to extend the area of our current in
      situ NMR investigations on thin electrically-switched or poled polymeric layers.
      The basic idea is to include synchronized electric pulses during the NMR
      experiment using the preparation and/or mixing periods of a 1D or 2D pulse
      sequence for the application of an orienting field (electric or magnetic) and to
      use the reversibility of the molecular switching phenomenon to achieve a
      sufficient signal-to-noise-ratio. The techniques extend the range of possible
      investigations from about 100 micros to approximately T1 for correlated spectra
      (and to longer times of applied fields for uncorrelated spectra). Results are
      shown for a nematic LC and a nematic polymer having a similar side chain.

PMID- 9603624
TI  - Double resonance experiments in a single resonance probe: detecting 23Na-51V
      dipolar interactions in sodium vanadates.
AB  - 23Na-[51V] double resonance TRAPDOR experiments are presented on two different
      sodium vanadates. This is the first time that the heteronuclear dipolar
      interaction between nuclei, whose Larmor frequencies lie within a range of 0 to 3
      MHz is detected in order to monitor connectivity and internuclear distance
      information in these systems.

PMID- 9603625
TI  - 14N NMR in AlN and BN.
AB  - A characterisation by 14N NMR of the binary nitrides AlN and BN is presented.
      Both the static and magic angle spinning (MAS) lineshapes have been investigated
      in order to determine, or set upper limits on, the nuclear quadrupole coupling
      (Cq) at the nitrogen site. Additional data are given for the Cq values at the Al
      and B sites. A comparison is made with other similar (mainly wurtzite) binary
      compounds for which Cq is known at each atomic site.

PMID- 9603626
TI  - Imaging of laser-polarized solid xenon.
AB  - The enhanced spin polarization produced by optical pumping of gaseous
      rubidium/xenon samples has made possible a number of recent experiments in
      nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance imaging
      (MRI). Here we report MRI of laser-polarized xenon in the solid phase at low
      temperature. Due to the high xenon density in the solid phase and the enhanced
      spin polarization, it is possible to achieve high intensity and spatial
      resolution of the image. Signals were observed from xenon films solidified onto
      the glass container walls and not from an enclosed chili pepper.

PMID- 9603627
TI  - Varicella-related deaths among children--United States, 1997.
AB  - During the first quarter of 1998, the Texas Department of Health and the Iowa
      Department of Public Health notified CDC of three fatal cases of varicella
      (chickenpox) that occurred in children during 1997. All three children were
      unvaccinated. Two children contracted chickenpox from unvaccinated siblings, and
      the mode of exposure was unknown for the third. This report summarizes these
      cases and indicates that varicella-related deaths continue to occur among
      children in the United States despite the availability of vaccine and
      recommendations for its use in all susceptible children.

PMID- 9603628
TI  - Pregnancy-related death associated with heparin and aspirin treatment for
      infertility, 1996.
AB  - In 1996, a 38-year-old nulliparous woman died from complications of a cerebral
      hemorrhage. She was approximately 9 weeks' pregnant with triplets at the time of
      her death. The patient had undergone in vitro fertilization (IVF) and was being
      treated with anticoagulants (heparin and aspirin) and intravenous immunoglobulin
      at the time of her death. This report summarizes the investigation of this case
      by state and county health departments with assistance from CDC.

PMID- 9603629
TI  - Population-based survey for drug resistance of tuberculosis--Mexico, 1997.
AB  - The World Health Organization (WHO) estimates that 90 million cases of
      tuberculosis (TB), resulting in 30 million deaths, will occur during the 1990s.
      To address this problem, WHO has recommended a comprehensive strategy of directly
      observed treatment, short-course (DOTS). Although DOTS results in cure rates of >
      or =80%, the worldwide emergence of strains of Mycobacterium tuberculosis (MTB)
      resistant to antimycobacterial agents threatens this strategy for TB control. In
      1994, WHO and the International Union Against Tuberculosis and Lung Disease
      (IUATLD) proposed the establishment of a global surveillance program to monitor
      drug resistance. In 1997, the Secretary of Health of Mexico, in collaboration
      with CDC, developed and implemented a national survey of drug resistance for TB
      as part of the global project on TB drug resistance. This report describes study
      results for three states in Mexico (Baja California, Oaxaca, and Sinaloa) and
      presents the first population-based TB drug-resistance data available for that
      country.

PMID- 9603630
TI  - Public Health Service guidelines for the management of health-care worker
      exposures to HIV and recommendations for postexposure prophylaxis. Centers for
      Disease Control and Prevention.
AB  - This report updates and consolidates all previous PHS recommendations for the
      management of health-care workers (HCWs) who have occupational exposure to blood
      and other body fluids that may contain human immunodeficiency virus (HIV); it
      includes recommendations for HIV postexposure prophylaxis (PEP) and discusses the
      scientific rationale for PEP. The decision to recommend HIV postexposure
      prophylaxis must take into account the nature of the exposure (e.g., needlestick
      or potentially infectious fluid that comes in contact with a mucous membrane) and
      the amount of blood or body fluid involved in the exposure. Other considerations
      include pregnancy in the HCW and exposure to virus known or suspected to be
      resistant to antiretroviral drugs. Assessments of the risk for infection
      resulting from the exposure and of the infectivity of the exposure source are key
      determinants of offering PEP Systems should be in place for the timely evaluation
      and management of exposed HCWs and for consultation with experts in the treatment
      of HIV when using PEP.

PMID- 9603631
TI  - Selecting antibacterial agents for the control of surgical infection: mini
      review.
AB  - An analysis of the recent literature on the control of surgical infections
      confirms the role of antimicrobial agents which guarantee valid perioperative
      antisepsis in both clean and clean-contaminated surgery. Current chemotherapy is
      able to check serious postoperative infectious complications by reducing the risk
      of septic shock with use of a glycopeptide-aminoglycoside-betalactam combination
      together with anti-inflammatory drugs.

PMID- 9603632
TI  - Immunopharmacology of oral betalactams.
AB  - Among the oral beta-lactam antibiotics only cefaclor has demonstrated a
      consistent in vitro and in vivo immunopharmacological effect which favors
      phagocytic chemotaxis and antimicrobial potential by inducing a T-helper 1 or pro
      inflammatory response. Together with cefpimizole, cefaclor significantly reduces
      the minimum bactericidal concentration (MBC) against some bacterial species when
      cultured together with a suspension of polymorphonuclear leukocytes, as opposed
      to some other oral beta-lactams, co-amoxiclav and cefixime, which do not show
      this effect. The pro-inflammatory component of cefaclor's activity explains the
      clinical success of this antibiotic in a high percentage of cases, even when
      laboratory tests indicate in vitro resistance by the pathogen.

PMID- 9603633
TI  - Imipenem resistance in aerobic gram-negative bacteria.
AB  - A prospective study was undertaken to observe the emergence of resistance to
      imipenem, if any, among aerobic gram-negative bacteria. A total of 736 isolates
      were tested during 1994-95 and less than 1% of them were resistant to imipenem,
      whereas the next year ('95-'96) the rate increased to 11 of the 903 isolates
      tested. The resistant isolates during '94-'95 were all Stenotrophomonas
      maltophilia whereas the spectrum of resistant bacterial species increased in '95
      '96 to include Pseudomonas aeruginosa, Burkholderia cepacia, Acinetobacter
      calcoaceticus, Enterobacter cloacae, Proteus mirabilis and Morganella morganii
      with a tendency to an increase in the minimum inhibitory concentration (MIC) in
      the later part of the year. A majority (72%) of the resistant isolates were from
      patients with burns, and burn wounds were most frequently infected with such
      organisms. These data suggest that over a period of time aerobic gram-negative
      bacteria may develop resistance to imipenem and the pool of such bacteria
      increases with extensive use of the drug. Non-fermentative aerobic bacteria tend
      to develop resistance faster with widespread dissemination than
      Enterobacteriaceae. Hospital Burn Units are a potential source of development of
      such resistance.

PMID- 9603634
TI  - Susceptibility to new beta-lactams of enterobacterial extended-spectrum beta
      lactamase (ESBL) producers and penicillin-resistant Streptococcus pneumoniae in
      Mexico.
AB  - The activities of several beta-lactam antimicrobial agents, aminoglycosides and
      ciprofloxacin, were determined against 62 clinical isolates of enterobacteria
      resistant to oxyimino cephalosporins (extended-spectrum beta-lactamase
      producers), collected during 1991 to 1993, and 16 penicillin-resistant invasive
      isolates of Streptococcus pneumoniae collected during 1994-1996. The numbers and
      percentages of susceptible enterobacterial strains to tested antibiotics were:
      imipenem 60 (97%), ciprofloxacin 57 (92%), cefepime 56 (90%), cefpirome 34 (55%),
      aztreonam 13 (21%), cefotaxime 7 (11%), ceftazidime 0 (0%), amikacin 11 (18%) and
      gentamicin 16 (26%). Despite the fact that these strains had never been exposed
      previously to cefepime or cefpirome, the susceptibility was 90% and 55%,
      respectively. No penicillin-resistant strains of S. pneumoniae were susceptible
      to cefotaxime, imipenem or cefepime. Only one strain was susceptible to
      ceftazidime and 4 (25%) were susceptible to cefpirome. Erythromycin showed the
      greatest activity with 12 (75%) susceptible strains.

PMID- 9603635
TI  - Meropenem compared with ceftazidime in the empiric treatment of acute severe
      infections in hospitalized children. Italian Pediatric Meropenem Study Group.
AB  - In a multicenter, randomized, open comparison of meropenem to ceftazidime as
      empiric treatment of severe acute infections, 185 children (1 mo-15 years old,
      mean 65.4 mo) were enrolled. Meropenem (20 mg/kg t.i.d. i.v.) was given to 98 and
      ceftazidime (10-30 mg/kg t.i.d. i.v.) to 87 children, generally for 5 to 10 days
      (mean: 6.9 for meropenem and 7.5 for ceftazidime). Clinical response was
      evaluated at the beginning and at the end of therapy and 4 weeks later (follow
      up). Clinical response was deemed satisfactory at the end of therapy in 96.7% of
      the patients treated with meropenem and in 95.3% of those who received
      ceftazidime without any statistically significant difference. One relapse
      occurred in a meropenem-treated patient at the follow-up clinical assessment. The
      baseline infecting organism was eradicated or presumed eradicated at the end of
      therapy in 14/16 patients treated with meropenem and in 14/15 treated with
      ceftazidime. The incidence of drug-related adverse events (mostly a slight
      increase in liver enzymes) was 9.2% in the meropenem group and 4.6% in the
      ceftazidime group. Our data show that meropenem is as effective as ceftazidime in
      the empiric treatment of severe infections in infants and children.

PMID- 9603636
TI  - Treatment of obstetric and gynecologic infections with meropenem: comparison with
      imipenem/cilastatin.
AB  - The aim of this study was to compare the clinical and bacteriologic efficacy of
      meropenem with imipenem/cilastatin in the treatment of obstetric and gynecologic
      infections. This was a controlled, multicenter, randomized study with two
      parallel groups and a follow-up period of up to 4 weeks. A total of 105 hospital
      in-patients requiring antibacterial parenteral therapy were enrolled, 52 in the
      meropenem group and 53 in the imipenem/cilastatin group. Both drugs were
      administered at 0.5 g every 8 hours, by slow intravenous infusion over 20-30
      minutes; for meropenem the administration by intravenous bolus injection (over
      approximately 5 minutes) was allowed. The mean duration of therapy was 5 days for
      both treatments. At the end of treatment, all 46 evaluable patients in the
      meropenem treatment group had a satisfactory clinical response, while in the
      imipenem/cilastatin group 5/49 patients were clinical failures. The difference
      between the treatment groups in clinical response was statistically significant
      (100% vs 89.8%; p=.026). A similar result was seen in the intention-to-treat
      analysis (98% vs 84.6%; p=0.017). Both treatments were well tolerated, but fewer
      meropenem patients experienced treatment-related adverse events in comparison
      with imipenem/cilastatin (11.5% vs 15.1%).

PMID- 9603637
TI  - Efficacy and safety of norfloxacin 800 mg once-daily versus norfloxacin 400 mg
      twice-daily in the treatment of uncomplicated urinary tract infections in women:
      a double-blind, randomized clinical trial.
AB  - Norfloxacin 400 mg twice-a-day has proven to be effective and safe in the
      treatment of uncomplicated urinary tract infections (UTI). Since previous
      pharmacokinetic studies demonstrate the feasibility of using norfloxacin 800 mg
      once-daily, and this scheme is assumed to improve patient compliance, a double
      blind randomized clinical trial was performed to compare the efficacy and safety
      of norfloxacin 800 mg once-daily (Group A) versus norfloxacin 400 mg twice-daily
      (Group B) in the treatment of adult female UTI for a 7-10 day period. Eighty-six
      adult women with clinical symptoms and urinary sediment signs suggestive of UTI
      were enrolled. In Group A, treatment was clinically assessed as effective in
      95.3% and bacteriologically effective in 92.0% of the patients. In Group B,
      clinical and bacteriological efficacy was 100% and 95.5%, respectively.
      Differences between groups are not statistically significant. Adverse events were
      reported by 14.0% of patients in Group A and 9.6% in Group B (difference not
      statistically significant). There was one withdrawal due to dizziness. In this
      study, norfloxacin 800 mg once-a-day was as effective and safe as norfloxacin 400
      mg twice-a-day in the treatment of uncomplicated urinary tract infections in
      women.

PMID- 9603638
TI  - Fatal suppurative mesenteric thrombophlebitis caused by an Enterococcus faecalis
      highly resistant to aminoglycosides: case report.
AB  - A 56-year old man with non-Hodgkin's lymphoma and biliary tract endoprosthesis,
      developed chronic bacteremia caused by Enterococcus faecalis with high-level
      resistance to gentamicin and streptomycin. The sources of bacteremia were a
      device-associated biliary tract infection, a suppurative thrombophlebitis of the
      confluence of the superior mesenteric vein with the splenic vein as well as
      multiple liver and pancreatic abscesses. Despite antibiotic therapy and multiple
      drainages of abscesses, the patient died due to overwhelming infection.

PMID- 9603639
TI  - Successful meropenem therapy of a brain abscess and meningitis arising from acute
      purulent otomastoiditis: case report.
AB  - We describe a case of a 25-year-old female with an acute left otomastoiditis,
      accompanied by a left temporal extradural abscess with moderate perifocal edema
      and meningitis. Intravenous meropenem (2 g 8-hourly) and intravenous
      methylprednisolone (40 mg once daily) were commenced empirically. Teicoplanin
      (400 mg once daily intravenously) was added after 5 days when culture results
      were available. Teicoplanin was discontinued on day 25 but meropenem and
      methylprednisolone were continued for a further 15 days, after which the abscess
      completely resolved without sequelae. No treatment-induced adverse effects or
      seizures were observed. Thus, in selected patients, antibacterials (in
      conjunction with a corticosteroid) may be successfully used without surgery to
      treat brain abscesses and in such circumstances meropenem is a useful option for
      empiric therapy.

PMID- 9603640
TI  - Optimal duration of chemotherapy in small cell lung cancer: a randomized study of
      4 versus 6 cycles of cisplatin-etoposide.
AB  - With the purpose of investigating whether the 6-course standard dose treatment of
      etoposide-platinum (EP) in small cell lung cancer could be reduced to 4 courses
      without compromising patient's survival, 70 patients were randomized to receive
      either 4 or 6 cycles of etoposide 120 mg/m2 i.v. days 1-3 and cisplatin 80 mg/m2
      day 1. With the intention of comparing these two durations as primary treatment
      policies, patients were randomized on admission and not after the fourth course.
      From the 69 evaluable patients 34 received EPx4 cycles and 35 EPx6 cycles.
      Objective response for EPx4 was achieved by 21 patients (62%, 95% CI 44%-78%)
      compared to 24 patients (69%, 95% CI 51%-83%) of the EPx6 group. Median times to
      progression were 6 mo (4-19) and 7 mo (4-40) respectively (P=0.06) in the two
      groups. Median survivals were 8.5 mo (4-28.5) and 9.5 mo (4-51) (p=0.04)
      respectively. No differences in the survival of limited-disease patients were
      shown with 10.5 mo (6-28.5) and 12 mo (8-51) respectively, in the two groups.
      Patients with extensive disease had a trend favoring prolonged chemotherapy with
      a median survival of 9 mo (5-16) versus 6.5 mo (4-16.5) for those in the EPx4
      group (p=0.09). Toxicity was not significantly more severe in the EPx6 group. In
      conclusion, patients achieving complete response within 4 cycles may not need
      continued chemotherapy, but patients with extensive disease may benefit from 2
      more cycles.

PMID- 9603641
TI  - Old and new chemokines. Pharmacological regulation of chemokine production and
      receptor expression: mini-review.

PMID- 9603642
TI  - CD8+ T lymphocyte-derived chemokines and other HIV-suppressive factors: mini
      review.

PMID- 9603643
TI  - Tachykinin receptors are present on human monocytes and play a role in rheumatoid
      arthritis.

PMID- 9603645
TI  - The role of IL-12 in the induction of an immune response to a tumor/self peptide:
      prevention and reversion of anergy.

PMID- 9603644
TI  - Role of peroxynitrite and poly (ADP-ribose) synthetase on cellular energy
      depletion in carrageenan-induced pleurisy.

PMID- 9603646
TI  - Induction of protective Th1 responses to Candida albicans by antifungal therapy
      alone or in combination with an interleukin-4 antagonist.

PMID- 9603647
TI  - Hepatocyte growth factor protects the liver against hepatitis C virus in patients
      on regular hemodialysis.

PMID- 9603648
TI  - Mechanism of renal damage in systemic autoimmune disorders.

PMID- 9603649
TI  - Suppression of adjuvant arthritis in rats by intraperitoneal Mycobacterium
      butyricum.

PMID- 9603650
TI  - Chronic viral hepatitis and interferon treatment: clinical experience in a series
      of 200 Italian patients.

PMID- 9603651
TI  - Therapeutic monitoring of tacrolimus in pediatric and adult transplanted
      patients.

PMID- 9603652
TI  - Association between the circadian course of endogenous noradrenaline and the
      hematopoietic cell cycle in mouse bone marrow.

PMID- 9603653
TI  - Modulation of intracellular calcium in human neutrophils by peripheral
      benzodiazepine receptor ligands.

PMID- 9603654
TI  - Does antiepileptic therapy affect immune response?

PMID- 9603656
TI  - Molecular biological methods for characterizing drug-metabolizing enzymes in
      hepatic and extrahepatic tissues.
AB  - Drug metabolism influences the pharmacotoxicological properties of a vast array
      of compounds and is controlled by a complex system of drug-metabolizing enzymes.
      A thorough understanding of this system allows the more effective development of
      therapeutic drugs as well as a significant improvement of risk assessment. The
      early identification of optimal therapeutic problems relating to drug metabolism
      could reduce the development costs for pharmaceuticals. Recently, techniques
      using transgenes have become available for this purpose. In these approaches the
      genetic information for the enzyme under investigation is expressed in vitro or
      in vivo, following gene transfer. This approach is called 'heterologous
      expression'. This article illustrates some examples in which molecular biological
      methods have been used to analyze those enzymes which control the
      pharmacotoxicological properties of drugs. Particular emphasis has been placed on
      the use of these methods to characterize extrahepatic drug-metabolizing enzymes
      such as those in the skin.

PMID- 9603655
TI  - Glucocorticoids: regulation of gene expression and apoptosis.

PMID- 9603657
TI  - Effects of systemic treatment with liarozole on cutaneous inflammation, epidermal
      proliferation and differentiation in extensive plaque psoriasis.
AB  - Liarozole is a novel inhibitor of the enzyme cytochrome P450 which has inhibitory
      effects on the 4-hydroxylation of retinoic acid. Previous studies have shown that
      liarozole is effective in the treatment of psoriasis. We performed an
      immunohistochemical study on the lesional skin from 7 patients with extensive
      plaque psoriasis, who were treated with systemic liarozole 75 mg BID for a period
      of at least 2 months. The effects of liarozole treatment on clinical and
      histological parameters were investigated. In particular, the effect of liarozole
      on the integrin markers CD11b and CD18 was studied. For immunohistochemistry,
      three consecutive biopsies were taken: before treatment, after 4, and after 8
      weeks of treatment. Clinical scores and side effects were recorded before and
      during treatment. The medication was well tolerated and only mild side effects
      were reported, which were comparable with hypervitaminosis A. After 2 months of
      treatment a statistically significant decrease of the extent of body involvement
      was observed. In the psoriatic plaque, markers for epidermal proliferation and
      cutaneous inflammation decreased, and markers for epidermal differentiation
      increased to values comparable to normal skin. The first therapeutic effects in
      the psoriatic plaque occurred after 4 weeks of treatment, and consisted of a
      decreased induration, accompanied by a decrease of the total number of
      inflammatory infiltrate cells and a decreased epidermal ICAM-1 expression.
      Already after 4 weeks of treatment, a decrease of CD11b-positive cells was
      observed. Subsequently, after 8 weeks of treatment recruitment of cycling
      epidermal cells and the number of involucrin-positive cell layers decreased. The
      present study demonstrates that liarozole treatment of psoriasis results in a
      reduction of aspects of cutaneous inflammation and subsequently a reduction of
      epidermal proliferation and promotion of differentiation. After 4 weeks of
      treatment, effects are observed on the epidermal ICAM-1 expression and on the
      CD11b-positive cell population.

PMID- 9603658
TI  - Relevance of hairless mouse as an experimental model of percutaneous penetration
      in man.
AB  - Since their first description in 1850, hairless mice have been widely used in
      scientific research. One major aspect of their use is skin pharmacology in
      general and skin penetration studies in particular. The term 'hairless mouse'
      does not distinguish a unique animal: it is a collective, descriptive name for a
      large group of different strains of various genetic origin. It is therefore
      important to precisely define the strain of mice used in a study. The available
      information on comparative penetration studies in man and in hairless mouse is
      sometimes contradictory. Some compounds will penetrate in an almost similar
      manner, whereas others differ in at least one logarithmic order, the human skin
      being the less permeable. Skin permeability is influenced, among others, by the
      physicochemical qualities of the compound under investigation. To obtain a
      clearer view on the suitability of the hairless mouse model in skin penetration
      studies, it should be useful to study this issue prospectively in a systematic
      fashion.

PMID- 9603659
TI  - In vivo human skin barrier modulation by topical application of fatty acids.
AB  - The in vivo effects of fatty acids on skin barrier function were assessed by
      measuring: (i) transepidermal water loss (TEWL), (ii) diffusion lag times for
      hexyl nicotinate (HN), and (iii) irritant skin response using laser Doppler
      velocimetry (LDV) in combination with visual scoring. Two classes of fatty acids
      have been investigated: straight-chain saturated fatty acids (SFA), having 6-12
      carbon atoms, and unsaturated fatty acids (UFA): oleic, linoleic, alpha-linolenic
      and arachidonic acids. It has been reported that these acids can enhance the
      permeation of various compounds across the skin. After topical and occlusive
      application as a solution in propylene glycol (PG) for 3 h on the volar arm of
      human subjects, SFA only caused a slight irritation and increase in TEWL. The
      diffusion lag times of HN were reduced by the application SFA to the same extent
      as and not more than by the application of the pure solvent PG. In contrast, the
      application of UFA caused a significant increase in TEWL and LDV (irritation)
      responses. The TEWL values after oleic acid application were higher than those
      observed for the other three acids, while the irritation potential of arachidonic
      acid was the highest among UFA. As with SFA, sites treated with UFA did not show
      significantly different lag times of HN diffusion from PC-treated sites. The data
      suggest that the degree of irritation and the degree of barrier modulation for
      fatty acids are not necessarily correlated.

PMID- 9603660
TI  - Iron overload augments 7,12-dimethylbenz(a)anthracene-initiated and 12-O
      tetradecanoylphorbol-13-acetate-promoted skin tumorigenesis.
AB  - Reactive oxygen species and free radicals have been implicated in the multistep
      cutaneous chemical carcinogenesis. Much of the experimental evidence in this
      regard is indirect and is based on observations that prooxidant status usually
      enhances and antioxidant treatments generally inhibit tumor yield. Iron overload
      is known to enhance peroxidative damage and cause oxidative stress. In this
      study, we report that iron overload augments 12-O-tetradecanoylphorbol-13-acetate
      (TPA)-mediated cutaneous tumor promotion. Female Swiss mice were subjected to
      iron overload by injecting 1 mg iron/ mouse/day consecutively for 2 weeks. Tumors
      were initiated by applying a single dose of 7,12-dimethylbenz(a)anthracene and
      promoted with twice weekly applications of TPA for 20 weeks and the appearance of
      first tumor (latency period), percent incidence and number of tumors per mouse
      were recorded. It has been observed that the level of iron in involved (tumor
      bearing) skin was about fourfold higher as compared to uninvolved (non-tumor)
      skin of iron overload animals and about tenfold higher as compared to the iron
      level in the skin of normal animals. When compared to the iron-unloaded control
      group, the iron overload mice showed an increased incidence of tumors. In iron
      overload animals, the tumors appeared 3 weeks earlier and also the number of
      tumors per mouse was significantly higher (2.5-fold). These data indicate that
      iron overload augments TPA-mediated tumor promotion. We propose that oxidative
      stress generated by iron overload may be responsible for the augmentation of
      cutaneous tumorigenesis.

PMID- 9603661
TI  - Effects of cetirizine dihydrochloride on human lymphocytes in vitro: evaluation
      of chromosome aberrations and sister chromatid exchanges.
AB  - The ability of cetirizine dihydrochloride, an antihistaminic agent, to induce
      chromosome aberrations as well as sister chromatid exchanges (SCEs) was evaluated
      in human lymphocyte cultures treated in vitro. The following concentrations were
      tested: 25, 50, 75, 100 and 200 micrograms/ml. The results of our study revealed
      that cetirizine dihydrochloride is capable of inducing chromosome aberrations, at
      least at the higher concentrations studied, 100 and 200 micrograms/ml. The
      majority of aberrations was of chromatid type. Cetirizine is also a weak inducer
      of SCEs. Further studies are now warranted in order to define the in vivo
      cytogenetic activity of cetirizine in humans.

PMID- 9603662
TI  - Effect of Avene spring water on the activation of rat mast cell by substance P or
      antigen.
AB  - The biological activity of Avene water from two different springs ('Sainte Odile'
      and 'Val d'Orb') was studied in vitro on rat peritoneal mast cell activation. A
      dilution-dependent inhibition of both histamine and prostaglandin D2 antigen
      induced release was observed when cells were preincubated with both Avene spring
      waters. They also inhibited histamine release triggered by substance P. The
      ability of Avene water to inhibit mast cell activation in vitro may be related
      with its antiallergic and anti-inflammatory properties and its use in
      hydrotherapy.

PMID- 9603663
TI  - Bioequivalence of topical dermatological dosage forms--methods of evaluation of
      bioequivalence. AAPS/FDA Workshop on 'Bioequivalence of Topical Dermatological
      Dosage Forms-- Methods of Evaluating Bioequivalence', September 4-6, 1996,
      Bethesda, Md.

PMID- 9603664
TI  - An update on vitamin D3 analogues in the treatment of psoriasis.
AB  - Vitamin D3 analogues have revolutionized the topical treatment of psoriasis
      during the last decade. The mode of action of this ligand for the vitamin D3
      receptor is via modulation of the transcription of genes with vitamin D3 response
      elements in their promoter region. Vitamin D3 analogues cause inhibition of
      various aspects of cutaneous inflammation and epidermal proliferation with
      enhancement of normal keratinization. In vivo, active vitamin D3 analogues proved
      to have a substantial antipsoriatic effect. Calcipotriol (50 micrograms/g in
      ointment or cream), tacalcitol (4 micrograms/g in ointment) and calcitriol (3
      micrograms/g in ointment) have been shown to have an antipsoriatic effect in
      placebo-controlled studies. The most extensive body of information on comparative
      studies and on combination therapies is available for the analogue calcipotriol.
      So far, calcipotriol is available as a routine treatment in most countries,
      whereas tacalcitol has been registered in Japan and some European countries. From
      the available data in the literature we may conclude that calcipotriol is a first
      line treatment for psoriasis and is advantageous in the combination with several
      other antipsoriatic treatments such as topical corticosteroids, PUVA, cyclosporin
      and acitretin. Tacalcitol 4 micrograms/g as a once-daily principle is effective
      in psoriasis. Comparative studies will indicate the position of the existing and
      new vitamin D3 analogues.

PMID- 9603665
TI  - Validation of freeze-drying to visualize percutaneous 3H-estradiol transport: the
      influence of skin hydration on the efficacy of the method.
AB  - A study was made of the validity of freeze-drying to visualize the distribution
      of 3H-estradiol in human stratum corneum after topical application of a dry dose,
      a patch or a buffer solution. Each of these donor formulations was applied to
      human dermatomed skin for 24 h using Franz permeation cells. Subsequently, small
      pieces of skin were subjected to cryofixation, freeze-drying, osmium tetroxide
      vapor fixation, Spurr resin embedding and electron microscopic autoradiography.
      Stratum corneum from dry dose and patch application experiments was well
      preserved by freeze-drying, allowing an accurate localization of 3H-estradiol. In
      contrast, stratum corneum from buffer solution experiments suffered from
      cryofixation artifacts due to excessive hydration of the skin. The corresponding
      autoradiographs showed strong redistribution of 3H-estradiol. Thus, the
      visualization method under investigation has its limitations regarding the
      hydration level of the skin.

PMID- 9603666
TI  - In vivo noninvasive evaluation of hairless rat skin after high-voltage pulse
      exposure.
AB  - Short high-voltage pulses have recently been shown to dramatically increase and
      expedite transdermal drug transport via a mechanism hypothesized to involve
      electroporation. This study addresses tolerance issues of the method in vivo in
      hairless rat. Chromametry, transepidermal water loss (TEWL), laser Doppler
      flowmetry (LDF) and corneometry were jointly used for noninvasive sensing of skin
      biophysical parameters. Slight increases in skin redness, TEWL and LDF values
      followed the application of electric pulses. The changes in skin capacitance were
      nonsignificant. The magnitude of the alterations depended on the electrical
      features of the pulses. When compared to iontophoresis, high-voltage pulses did
      not induce stronger alterations of skin functions. This report provides the first
      in vivo demonstration of the safety of the high-voltage pulses proposed for
      transdermal delivery.

PMID- 9603667
TI  - Percutaneous absorption of methylprednisolone aceponate following topical
      application of Advantan lotion on intact, inflamed and stripped skin of male
      volunteers.
AB  - Six healthy, elderly volunteers received three topical treatments with Advantan
      lotion containing 0.1% of methylprednisolone aceponate (MPA, CAS 86401-95-8) on
      intact, inflamed and stripped skin in a consecutive fashion at weekly intervals.
      The lotion (O/W emulsion) containing 14C-MPA (specific radioactivity 1.8 MBq/mg
      MPA) was applied in an area dose of 5 mg lotion/cm2 on a marked area of 100 cm2
      on the back for 24 h. Inflammation was caused by UV-B irradiation at 3 MED 6 h
      prior to the treatment with the test preparation. Removal of stratum corneum was
      performed by 20-fold adhesive tape stripping. The concentration of radioactivity
      was measured in the plasma and in the urine up to 7 days following each
      treatment. The concentration of radioactivity in the plasma did not exceed the
      limit of detection of 1.5 ng MPA Eq/ml at any time point. The percutaneous
      absorption was assessed from the cumulated excretion of radiolabelled substances
      in the urine corrected for biliary excretion. Less than 0.5% of the dose was
      percutaneously absorbed through intact skin and through inflamed skin. After
      removal of the penetration barrier ('stripping') the percutaneous absorption
      increased to 15.4 +/- 7.7% of the applied dose.

PMID- 9603668
TI  - Effects of mometasone furoate on human keratinocytes and fibroblasts in vitro.
AB  - The long-term treatment of inflammatory skin diseases with topical
      glucocorticoids is limited by their side effects such as skin atrophy, delayed
      wound healing and striae distensae. Mometasone furoate (MF) is a newly
      synthesized glucocorticoid with the advantage of increasing efficacy and reducing
      the number of adverse effects. The aim of our study was to compare the effects of
      MF and conventional fluorinated corticosteroids on a human keratinocyte cell line
      (HaCat) and human skin fibroblasts in vitro. Monolayer cultures of these cell
      lines were exposed to different concentrations of the active compounds for 5 days
      to analyze the influence on morphology and proliferation. Chemotaxis of HaCat
      cells and fibroblasts was studied in blind-well Boyden chambers using collagen
      type I and fibroblast-conditioned medium as a chemoattractant. Additionally,
      fibroblasts were used to investigate the contraction of collagen gels since
      lattice contraction appears to model the contraction of skin wounds. All
      glucocorticoids tested influenced fibroblast and keratinocyte proliferation in a
      dose-dependent manner, yet the effect was clearly more marked with fluorinated
      corticosteroids than with MF. Similar effects were obtained using the chemotaxis
      assay. At low concentrations (10(-9) M) MF exerted almost no influence, while the
      conventional fluorinated substances inhibited direct migration significantly.
      Contraction of collagen gels was inhibited completely by betamethasone valerate
      at high concentrations (10(-5)-10(-3) M), but only partially inhibited by MF at
      its highest concentration (10(-3) M). Although MF reveals high anti-inflammatory
      activity similar to that known for conventional fluorinated derivatives of
      corticosteroids, the study shows that MF has less effect in the tested in vitro
      systems. Therefore, it remains to be seen whether these data might indicate the
      possibility of a dissociation between the inflammatory activity and the
      inhibition of the biosynthetic capacities of fibroblasts and keratinocytes by
      modification of the steroidal structure of corticosteroids.

PMID- 9603669
TI  - Histometric assessment of the age-related skin response to 2-hydroxy-5-octanoyl
      benzoic acid.
AB  - Only a handful of topical products have been shown to limit or improve age
      related skin damage. 2-Hydroxy-5-octanoyl benzoic acid, also designated beta
      lipohydroxyacid (beta-LHA), is among the active molecules claiming such effects.
      The present randomized placebo-controlled double-blind study was undertaken to
      evaluate the effects of beta-LHA in young and older women. Both groups responded
      to the beta-LHA-containing formulation, although to different degrees according
      to age and the biologic parameter considered. Topically applied 1% beta-LHA
      formulation was associated with several changes, the most conspicuous ones being
      epidermal thickening and dendrocytic hyperplasia. The constellation of biologic
      modifications remained within physiological limits, close to the characteristics
      of young skin. It is inferred that topical beta-LHA can cause a significant
      improvement in some epidermal and dermal manifestations of ageing.

PMID- 9603671
TI  - [The 38th annual meeting of the Japanese Respiratory Society. Kumamoto City,
      Japan. March 30-31, April 1, 1998. Abstracts].

PMID- 9603670
TI  - Microsomes, drug oxidation, and clinical pharmacology. Satellite symposium
      following the 2nd Congress of the European Association for Clinical Pharmacology
      and Therapeutics (EACPT).

PMID- 9603672
TI  - Toward an improved behavioral medicine.
AB  - Never before have the challenges for behavioral medicine been more exciting or
      more urgent. Because most health problems have their roots in behavioral causes,
      the role of behavioral medicine is paramount in public health. The challenges
      focus both on issues related to the way researchers interact, set priorities, and
      conduct research, as well as priority areas for future research. The principles
      include a need for more theoretical diversity and critique of theory, more
      inclusiveness, more cost-consciousness, an acceptance of failure as a fundamental
      part of behavioral science, and a greater commitment to international health. The
      priorities encompass a greater focus on basic behavioral science, more attention
      to the study of risk perception, more study of the problems of children and aging
      populations, and an urgent need for proven, proactive interventions.
      Actualization of these principles could help behavioral medicine researchers and
      practitioners to achieve a much greater impact in improving the public's health
      both in the U.S. and abroad.

PMID- 9603673
TI  - Beyond good and bad coping: a multidimensional examination of coping with pain in
      persons with rheumatoid arthritis.
AB  - This article examines the utility of using a multidimensional instrument to
      assess pain coping in two samples of persons with rheumatoid arthritis (total N =
      378). The predictive validity of the newly developed Vanderbilt Multidimensional
      Pain Coping Inventory (VMPCI), which assesses eleven distinct coping strategies,
      was compared to that of the previously validated Vanderbilt Pain Management
      Inventory (VPMI), which assesses the two broad dimensions of active and passive
      coping. In both samples, the VMPCI demonstrated reliable incremental validity
      over the VPMI in predicting both positive and negative psychological adjustment,
      and the predictive ability of the VPMI was highly redundant with that of the
      VMPCI. Moreover, using the VMPCI, both positive and negative adjustment were
      related to multiple coping strategies in ways that could not be revealed by the
      VPMI. These results offer considerable validation to the VMPCI and illustrate the
      value of assessing coping multidimensionally.

PMID- 9603674
TI  - Coping strategies and laboratory pain in children with sickle cell disease.
AB  - Studies have found that coping strategies are significant predictors of pain
      report, health care use, and psychosocial adjustment in children with sickle cell
      disease (SCD); however, the mechanisms of the relationship are not clear. In this
      study, 41 children with SCD completed a laboratory pain task to analyze their
      pain perception under standardized conditions. Sensory decision theory analyses
      were used to analyze the pain perception data. Children and their parents also
      completed measures of coping strategies and adjustment. Hierarchical regression
      analyses controlling for the child's age indicated that children who reported
      using active cognitive and behavioral coping strategies had a lower tendency to
      report pain during the laboratory pain task. Results are discussed in terms of
      the utility of using laboratory pain models with children and the need for future
      intervention studies to target coping strategies in children with SCD pain.

PMID- 9603675
TI  - Health beliefs, personality, and adherence in hemodialysis patients: an
      interactional perspective.
AB  - Research examining the main effects of health beliefs and personality on medical
      regimen adherence has yielded inconsistent results. This study tested the
      hypothesis that health beliefs and personality predict adherence in an
      interactive manner. Components of the Health Beliefs Model, Conscientiousness (C)
      from the NEO-Five Factor Inventory, and regimen adherence were assessed in a
      sample of 70 in-center hemodialysis patients. In a hierarchical regression
      analysis, the interaction of health beliefs and C failed to explain a significant
      portion of the variance in interdialysis weight gain, a measure of adherence to
      fluid restrictions, after controlling for demographic characteristics. The
      interaction did significantly predict individual differences in serum phosphorus
      levels, a measure of diet and medication adherence. The effect was primarily
      attributable to the interaction of C and perceived severity. However, the
      combination of high C and high perceived severity was associated with poorer
      patient adherence. Such a pattern may be the result of defective coping patterns
      associated with high levels of anxious arousal and has implications for
      therapeutic interventions targeted at modifying health beliefs among chronically
      ill patients following prescribed medical regimens.

PMID- 9603676
TI  - Correlates of HIV risk appraisal in women.
AB  - This study examined the relationship of safer sex behavior practices, knowledge
      of acquired immunodeficiency syndrome (AIDS), social norms, and familiarity with
      persons infected with the human immunodeficiency virus (HIV) with HIV risk
      appraisal in women. Risk appraisal was measured by perceived susceptibility and
      seriousness of AIDS. The AIDS Risk Reduction Model was used to construct a
      salient framework for this descriptive, correlational survey in which 208 urban
      women of mixed ethnicity residing in areas with high rates of sexually
      transmitted diseases/AIDS participated. Behavior, knowledge, and social norms,
      contributed significant amounts of variance to perceived susceptibility but none
      of the independent variables contributed significant amounts of variance in
      perceived seriousness. Overall findings indicate that risk behaviors are commonly
      reported. AIDS knowledge is incomplete, and denial of risk is pronounced.

PMID- 9603677
TI  - Cigarette smoking predicts development of depressive symptoms among U.S.
      adolescents.
AB  - To examine whether adolescent cigarette smoking predicts the development of
      depressive symptoms, we used a longitudinal follow-up survey of 6,863 adolescents
      ages 12 to 18 in the U.S. who did not report notable depressive symptoms at
      baseline. This study used a self-report measure of six depressive symptoms
      experienced within the past twelve months at follow-up as the outcome of
      interest. Results indicated that 11.5% developed notable depressive symptoms at
      follow-up. There were marked gender differences with 15.3% of girls developing
      notable depressive symptoms compared to 8.1% of boys. Gender differences in
      depressive symptoms were consistent across all age groups and were apparent by
      the age of twelve. For both genders, smoking status was the most significant
      predictor of developing notable depressive symptoms. Several other risk factors
      including involvement in organized athletics, availability of social support, and
      personality characteristics were also found to be associated with development of
      depressive symptoms. Adolescent cigarette smoking may have marked health
      consequences in terms of depressive symptoms. The reduction of cigarette smoking
      among adolescents should be a focus of depression prevention interventions. In
      addition, the development of gender-specific components of prevention
      interventions may be warranted.

PMID- 9603678
TI  - Perceptions of control, physical exercise, and psychological adjustment to breast
      cancer in South African women.
AB  - Psychological adjustment and locus of control were measured in 257 South African
      women both with and without breast cancer. Adjustment was defined as positive
      affect, negative affect, the balance between the two, satisfaction with various
      domains of life, and an overall sense of well-being. Health locus of control was
      measured separately for internal, external, and chance loci. The instrument's
      reliability was comparable to that reported for U.S. norms. The women with breast
      cancer reported significantly lower affect and had lower internal and higher
      external and chance perceptions of control. The more invasive the surgical
      treatment, the greater the negative impact on adjustment. Data suggested that
      using written instructions to stress the importance of exercise to rebuild arm
      strength immediately following the surgery had a long-lasting positive impact on
      affect. Side of intervention was also related to psychological adjustment.
      Significant differences across racial groups were found for both adjustment and
      health locus of control.

PMID- 9603679
TI  - Anger suppression, reactivity, and hypertension risk: gender makes a difference.
AB  - The present study investigated gender-related differences in cardiovascular
      reactivity and the role of anger inhibition and risk for future hypertension.
      Tonic blood pressure served as an index of hypertension risk. Twenty-eight female
      and 26 male college students with high and low normal blood pressure were
      recruited on the basis of their mean arterial pressure. Continuous measures of
      heart rate and blood pressure were taken while participants carried out a series
      of behavioral manoeuvres including mental arithmetic, interpersonal challenge, a
      frustrating psychomotor test, and the cold pressor test. Participants also
      completed inventories assessing trait anxiety, trait anger, anger expression, and
      Type A. The results are in concordance with previous findings and show higher
      cardiovascular reactivity in men than in women and in subjects at risk for
      hypertension. Within the male group, a combination of hypertension risk and anger
      suppression led to the highest reactivity, whereas in female subjects,
      differences in anger-in had no effect on reactivity. The implications of these
      results are discussed in light of sex differences in cardiovascular morbidity and
      mortality.

PMID- 9603680
TI  - Physiological and physical concomitants of caregiving: introduction.

PMID- 9603681
TI  - Chronic stress modulates the virus-specific immune response to latent herpes
      simplex virus type 1.
AB  - We compared 71 family caregivers of dementia sufferers and 58 control subjects on
      three different immune measures relevant to latent herpes simplex virus Type 1
      (HSV-1) infection: neutralizing antibody titers, antibody titers to a total viral
      antigen, and a proliferative memory T-cell response. Caregivers had significantly
      higher antibody titers to the total viral antigen and a poorer HSV-1 specific T
      cell response than controls, but no significant difference in neutralizing
      antibody titers between groups was observed. These data provide additional
      evidence that psychological stress can modulate a virus-specific immune response
      associated with caregiving.

PMID- 9603682
TI  - Alzheimer caregiver stress: basal natural killer cell activity, pituitary-adrenal
      cortical function, and sympathetic tone.
AB  - The association between Alzheimer caregiving and natural killer (NK) cell
      activity and basal plasma levels of adrenocorticotropic hormone (ACTH), cortisol,
      beta-endorphin, prolactin, epinephrine, norepinephrine, and neuropeptide Y was
      determined in 100 spousal Alzheimer caregivers and 33 age- and gender-comparable
      control volunteers upon intake into a study of the psychological and physiologic
      impact of caregiving. The relationship between these physiologic measures and
      individual characteristics such as age, gender, medical status, severity of
      stress, severity of depressive symptoms, and caregiver burden was tested. In
      addition, the association between NK activity and alterations of the
      neuroendocrine measures was investigated. As compared to controls, the Alzheimer
      caregivers had similar levels of NK activity and of basal plasma neuroendocrine
      hormones and sympathetic measures. While older age and male gender status were
      associated with increased levels of ACTH, neither medical caseness, severity of
      life stress, nor severity of depressive symptoms was associated with alterations
      in any of the multiple physiologic domains. Classification of Alzheimer caregiver
      burden identified caregivers who were mismatched in terms of the amount of care
      they were required to provide and the amount of respite time received. The
      mismatched caregivers had significantly higher basal plasma ACTH but no change in
      other physiological measures, as compared to non-mismatched caregivers. NK
      activity was negatively correlated with plasma levels of neuropeptide Y but not
      with any of the other neuroendocrine measures. Based on this cross-sectional
      evaluation of NK activity and neuroendocrine and sympathetic measures, we
      conclude that most Alzheimer caregivers do not show evidence of altered basal
      physiology.

PMID- 9603683
TI  - Enhancing physical and psychological functioning in older family caregivers: the
      role of regular physical activity.
AB  - Although informal caregiving among older adults creates a range of physical and
      psychological burdens for the caregiver, little research has been directed at
      evaluating strategies for preserving caregivers physical functioning in addition
      to their psychological well-being. The purpose of the current research was to
      examine, through population-based survey sampling procedures, levels of physical
      activity and related health practices and preferences among a random sample of
      older family caregivers; evaluate, using an experimental design, the feasibility
      of initiating a four-month supervised home-based moderate-intensity physical
      activity regimen among older family caregivers; and explore the potential effects
      of physical activity on anger expression, caregiver burden, and related
      psychological outcomes in this population. The results suggest that: (a) physical
      inactivity is a prevalent risk factor among family caregivers that requires
      systematic attention; (b) a significant proportion of family caregivers of both
      sexes are interested in improving their physical activity levels, especially
      through programs that do not require ongoing attendance at a class or group; and
      (c) supervised home-based programs that focus on brisk walking and similar
      moderate-intensity physical activities appear to be both feasible and potentially
      beneficial in health (e.g. ambulatory blood pressure) as well as mental health
      (e.g. anger expression) areas.

PMID- 9603684
TI  - Longitudinal analysis of multiple indicators of health decline among spousal
      caregivers.
AB  - The hazards for experiencing major health events were studied longitudinally
      among 150 spousal caregivers of Alzheimer's disease (AD) patients and 46 married
      control participants. Based on longitudinal assessments from one to six years,
      the hazards of reaching any of three health events (extended physical illness or
      disability > 1 month, unhealthy medical rating from a nurse interview, or
      hospitalization) were not significantly different in a group comparison of
      caregivers to controls (Cox proportional hazards assumption, p > .05). However,
      there was a trend [X2(1, N = 107) = 3.13, p = .08] for caregivers to have a
      greater hazard for serious illness. Among caregivers only, a greater hazard for
      reaching at least one of these health events was associated with providing more
      activities of daily living (ADL) assistance [X2(1, N = 125) = 3.83, p = .05] but
      not with problem behaviors of the AD patient (p > .05). These results suggest
      that providing extensive ADL assistance may have health implications for spousal
      AD caregivers, while caregiving, per se, does not. Furthermore, these physical
      health impacts of caregiving may be best characterized using multidimensional
      assessments. Contrary to our guiding hypothesis, caregivers encountering more
      problem behaviors of their AD spouse were less likely to be hospitalized, X2(1, N
      = 145) = 5.88, p = .02. This finding may reflect a reluctance by caregivers to
      schedule necessary medical care when their spouses are most problematic, and this
      may have further long-term health implications for caregivers.

PMID- 9603685
TI  - Health effects of caregiving: the caregiver health effects study: an ancillary
      study of the Cardiovascular Health Study.
AB  - We propose that two related sources of variability in studies of caregiving
      health effects contribute to an inconsistent pattern of findings: the sampling
      strategy used and the definition of what constitutes caregiving. Samples are
      often recruited through self-referral and are typically comprised of caregivers
      experiencing considerable distress. In this study, we examine the health effects
      of caregiving in large population-based samples of spousal caregivers and
      controls using a wide array of objective and self-report physical and mental
      health outcome measures. By applying different definitions of caregiving, we show
      that the magnitude of health effects attributable to caregiving can vary
      substantially, with the largest negative health effects observed among caregivers
      who characterize themselves as being strained. From an epidemiological
      perspective, our data show that approximately 80% of persons living with a spouse
      with a disability provide care to their spouse, but only half of care providers
      report mental or physical strain associated with caregiving.

PMID- 9603686
TI  - Research on physiological and physical concomitants of caregiving: where do we go
      from here?
AB  - This article discusses the current state of research on the physiological and
      physical concomitants of caregiving. We offer recommendations about theoretical,
      empirical, and treatment issues that researchers should consider in future
      investigations. Important theoretical issues include specifying acute and chronic
      stress in caregiving research. Empirical issues include sample selection, home
      versus clinic assessments, the use of experimental probes, moderating and
      mediating variables, and measurement issues (problems with self-report of health,
      medical records, physical exams, and lab assessments). Finally, we note that
      investigators should use this newfound knowledge to target interventions to
      specific subsets of vulnerable caregivers. In this way, basic research into
      caregiving, as a model of chronic human stress, can provide more focused
      approaches to benefit both caregivers and patients.

PMID- 9603687
TI  - Detecting panic disorder in emergency department chest pain patients: a validated
      model to improve recognition.
AB  - OBJECTIVE: To develop and validate a detection model to improve the probability
      of recognizing panic disorder in patients consulting the emergency department for
      chest pain. METHODS: Through logistic regression analysis, demographic, self
      report psychological, and pain variables were explored as factors predictive of
      the presence of panic disorder in 180 consecutive patients consulting an
      emergency department with a chief complaint of chest pain. The detection model
      was then prospectively validated on a sample of 212 patients recruited following
      the same procedure. RESULTS: Panic-agoraphobia (Agoraphobia Cognitions
      Questionnaire, Mobility Inventory for Agoraphobia), chest pain quality (Short
      Form McGill Pain Questionnaire), pain loci, and gender variables were the best
      predictors of the presence of panic disorder. These variables correctly
      classified 84% of chest pain subjects in panic and non-panic disorder categories.
      Model properties: sensitivity 59%; specificity 93%; positive predictive power
      75%; negative predictive power 87% at a panic disorder sample prevalence of 26%.
      The model correctly classified 73% of subjects in the validation phase.
      CONCLUSION: The scales in this model take approximately ten minutes to complete
      and score. It may improve upon current physician recognition of panic disorder in
      patients consulting for chest pain.

PMID- 9603688
TI  - Eating behavior following stress in women with and without bulimic symptoms.
AB  - OBJECTIVE: This study examined the effects of an interpersonal stressor on
      subsequent calorie intake in females with (N = 20) and without (N = 20)
      significant bulimic symptomatology. METHOD: Subjects participated in two
      laboratory sessions that differed according to experimental condition (stress
      versus no stress), completed self-report measures of mood and anxiety before and
      after the experimental task, and were provided with an array of snack foods after
      each session. RESULTS: Counter to the hypothesis, women with bulimic symptoms did
      not differentially increase their intake when exposed to stress. However, results
      for the intake of each macronutrient indicated that both bulimic and control
      women increased their consumption of carbohydrates following the stressor. Thus,
      stress was related to increased carbohydrate consumption by all subjects but did
      not differentially affect the consumption of women with bulimic symptoms.
      CONCLUSIONS: It may be that women with bulimic symptoms are not differentially
      vulnerable to eating in response to stress or that current laboratory paradigms
      are unable to detect differences in eating following a stressor.

PMID- 9603689
TI  - Social relationships and immune processes in HIV seropositive gay and bisexual
      men.
AB  - This three-year longitudinal study assessed the association between social
      relationships and human immunodeficiency virus (HIV) progression in individuals
      at risk for morbidity and mortality due to acquired immune deficiency syndrome
      (AIDS). Two-hundred five HIV seropositive men without AIDS completed measures of
      social integration and loneliness at baseline. Blood samples used to assess CD4 T
      lymphocyte levels were collected at baseline and at six-month intervals for a
      three-year follow-up period. Contrary to expectation, lower levels of baseline
      loneliness predicted more rapid declines in CD4 levels over the follow-up period.
      This association was independent of baseline CD4 values, negative affect, and
      health practices. A series of mediational analyses revealed that sexual behavior,
      medication use, bereavement, coping, and a number of other variables were not
      mechanisms through which loneliness affected the immune system. Loneliness was
      not associated with time to AIDS diagnosis or time to AIDS-related mortality.
      These findings are consistent with the emerging view that social relationships
      can have deleterious, as well as protective, influences on health outcomes.

PMID- 9603690
TI  - Functional decline in the elderly: evidence for direct and stress-buffering
      protective effects of social interactions and physical activity.
AB  - Advances in medical technology and improvements in health behavior have greatly
      increased the proportion of Americans who survive into old age. Consequently,
      identifying environmental and behavioral factors that enhance or protect the
      health and functional capacity of older adults is an important goal. This study
      investigated the extent to which social interactions and physical activity can
      protect older adults from the declines in functional ability that typically occur
      with age and the extent to which they buffer the negative effects of widowhood on
      physical functioning. Data were from the Longitudinal Study of Aging, a six-year
      follow-up of over 7,000 respondents in the 1984 National Health Interview Survey.
      Using individual growth curve models which examine the effects of predictor
      variables on change over time, this study investigated how physical activity,
      social interactions, and widowhood are related to the rate of change in
      functional health over a six-year period. Results suggested that physical
      activity and social interactions each exerted independent effects on functional
      decline. In addition, physical activity and social interactions buffered the
      effects of widowhood on functional decline, especially in men who died before the
      end of the study. Results suggest a need for health promotion programs to
      encourage both physical and social activities in the elderly.

PMID- 9603691
TI  - A dual pathway model of daily stressor effects on rheumatoid arthritis.
AB  - This study evaluated the initial promise of a dual-pathway conceptual model
      linking daily event stressors to rheumatoid arthritis (RA) disease activity
      through changes in immune system activation and mood. Fifty individuals, who were
      studied on five occasions two weeks apart, reported daily event stressors on the
      Daily Life Experience Checklist, daily mood on an abbreviated version of the
      Profile of Mood States-B, and daily joint pain on the Rapid Assessment of Disease
      Activity in Rheumatology. Serial clinical examinations comprised ratings of joint
      tenderness and swelling, and blood drawn during exams was analyzed for
      sedimentation rate (an indicator of systemic inflammation) and soluble
      interleukin-2 receptors (a marker of immune system activation known to correlate
      with RA disease activity). Across-person analyses failed to establish links from
      daily event stressors to either disease activity or composites of joint pain and
      joint inflammation when associations were adjusted for the effect of neuroticism
      on self-report measures. Pooled within-person analyses, however, were generally
      consistent with the relations predicted by the dual-pathway model. Increases in
      daily event stressors during the week preceding each clinical exam were
      associated with increased joint pain (regardless of changes in mood). At the same
      time, increased daily stressors were indirectly associated with decreased joint
      inflammation through reduction in levels of soluble interleukin-2 receptors. The
      dual-pathway model, which may be limited to short-term psychological and
      psychoimmunologic processes, underscores the importance of distinguishing
      potentially opposing effects of stress on pain versus inflammation in individuals
      with rheumatoid arthritis.

PMID- 9603692
TI  - Psychosocial determinants of health care utilization in sickle cell disease
      patients.
AB  - This article reviews the literature on psychosocial factors associated with
      sickle cell disease and health care utilization. The Health Belief Model is
      proposed as a framework that may help guide our understanding about how these
      variables influence health care utilization. Since the existing literature on
      psychosocial variables and health care utilization among sickle cell disease
      patients is scant, studies from related behavioral medicine research will be
      presented as a basis for future research. This review suggests that identifying
      modifiable psychosocial variables associated with utilization could aid in the
      development of interventions aimed at reducing utilization and thereby reducing
      health care costs.

PMID- 9603693
TI  - The association between anger and hostility and risk factors for coronary heart
      disease in children and adolescents: a review.
AB  - We reviewed the published literature on the association between anger and
      hostility and risk factors, both physiologic and behavioral, for coronary heart
      disease (CHD) in youth. The rationale for this review is based on observations
      that pathology and risk factors associated with CHD in adults, as well as
      patterns of expressing anger and hostility, often begin in childhood and
      adolescence; hence, it is imperative that we better understand the relationship
      between anger and CHD risk factors in young people if we are to develop
      interventions to change risk factor profiles. The first section discusses
      development of CHD risk factors and describes studies of the pathologic
      precursors of CHD that demonstrate the early age of onset for pathologic changes,
      the tracking of physiologic and behavioral risk factors from youth to adulthood,
      and the young age of initiation of behavioral risk factors associated with CHD.
      The second section discusses both the development and tracking of the constructs
      of anger and hostility. The third section provides a review of the epidemiologic
      studies that assess the association between anger or hostility and both
      physiologic and behavioral CHD risk factors among school-age children. The final
      section provides an analysis and synthesis of the preceding sections and makes
      suggestions for further research.

PMID- 9603694
TI  - Making cardiovascular disease prevention a reality.

PMID- 9603695
TI  - Diet and cardiovascular disease prevention: what works?
AB  - Diet is routinely recommended as the primary strategy for the prevention and
      treatment of high blood cholesterol. The National Cholesterol Education Program
      (NCEP), the American Heart Association (AHA), and a host of other health and
      medical organizations have advocated a diet low in total and saturated fat and
      cholesterol for reducing risk of cardiovascular disease. What is the evidence
      supporting these guidelines and the expected efficacy of dietary treatment? There
      is growing awareness that despite well-documented rationale for the dietary
      approach, many eligible patients are not routinely prescribed dietary treatment,
      and among those who are, there is limited response. What are the obstacles in
      implementing effective dietary intervention for prevention of cardiovascular
      disease? What are both the theoretical and practical limitations to achieving
      long-term adherence to diet and what strategies have been shown to be most
      effective? A review of the data surrounding these diet-lipid relationships is
      presented along with recently tested and promising behavioral approaches to
      facilitating patient adherence.

PMID- 9603696
TI  - Smoking cessation: principles and practice based upon the AHCPR Guideline, 1996.
      Agency for Health Care Policy and Research.
AB  - Cigarette smoking remains the leading preventable cause of morbidity and
      premature mortality in the United States. Although the vast majority of smokers
      come in contact with the health care system on a regular basis, clinical smoking
      cessation interventions happen infrequently and in a non-systematic manner. In
      1996, the Agency for Health Care Policy and Research (AHCPR) "Smoking Cessation
      Clinical Practice Guideline" provided detailed clinical practice recommendations
      based on a review of some 3,000 articles in the research literature and dozens of
      supporting meta-analyses. This article presents a simple four-step model for
      clinical smoking cessation interventions, including systematic identification of
      smoking status, brief cessation advice from clinicians, assessment of patient
      motivation, and detailed assistance for those willing to stop smoking. It also
      provides the empirical basis for the AHCPR Guideline recommendations.

PMID- 9603697
TI  - Exercise and its role in the prevention and rehabilitation of cardiovascular
      disease.
AB  - The purpose of this article is to review the beneficial effects of regular
      exercise in the primary and secondary prevention of coronary artery disease
      (CAD). Epidemiologic studies indicate that a physically inactive life-style is
      associated with twice the risk of developing CAD. The magnitude of risk is
      similar to that of other modifiable risk factors. Meta-analysis of studies of
      cardiac rehabilitation after myocardial infarction demonstrate that cardiac
      rehabilitation participants lower their risk of death by 20% to 25% compared to
      controls. Exercise training results in several beneficial physiological changes
      including an increase in exercise endurance, higher resting and exercise stroke
      volumes, lower resting and submaximal exercise heart rates, and increased
      capillary density and oxidative enzyme capacity in skeletal muscle. In patients
      with established CAD, exercise training improves symptoms of angina and
      congestive heart failure and attenuates the severity of exercise-induced
      ischemia. Regular exercise can favorably modify other risk factors, but the
      benefits are modest. Reductions in systolic and diastolic blood pressure readings
      average 6 to 9 mm Hg; decreases in total and low-density lipoprotein (LDL)
      cholesterol approximate 5 to 10 mg/dL; and increases in high-density lipoprotein
      (HDL) cholesterol approximate 2 mg/dL. Exercise training as a sole intervention
      does not appear to enhance smoking cessation. Regular exercise does improve
      psychosocial well-being. Most studies of physical activity have enrolled
      predominantly middle-aged men; however, available evidence suggests similar
      cardiovascular benefits for women, the elderly, and children and youth. Physical
      activity levels decrease substantially during the school-age-adolescent
      transition in both males and females. More than half of the adult population is
      sedentary or inactive. Collectively, accumulated data suggest the need for both
      individualized/high-risk and population-based approaches to increasing physical
      activity across the life span.

PMID- 9603698
TI  - Behavioral issues in the efficacy versus effectiveness of pharmacologic agents in
      the prevention of cardiovascular disease.
AB  - A number of pharmacologic interventions are now recommended for the prevention of
      cardiovascular disease, based on the results of randomized controlled trials.
      These include antihypertensive drugs, lipid-lowering agents, antiplatelet and
      anticoagulant drugs, estrogen replacement therapy, beta-blockers, and angiotensin
      converting enzyme (ACE) inhibitors. It is likely that additional pharmacologic
      interactions will soon be proven efficacious. Despite the strength of this
      evidence and the development of clinical guidelines incorporating their use, a
      surprisingly low proportion of patients are actively treated with these agents.
      There may be a variety of explanations for this, including barriers at the level
      of the patient, health care provider, and health care institution. Finally, a
      number of questions remain as to the optimal combination of interventions, both
      behavioral and pharmacologic, which will yield maximal reduction in risk. The
      description of factors which reduce the effectiveness of pharmacologic
      interventions below the efficacy demonstrated in randomized clinical trials
      should be a fertile area for epidemiologic and behavioral research.

PMID- 9603699
TI  - Compliance with cardiovascular disease prevention strategies: a review of the
      research.
AB  - The efficacy of cardiovascular risk-reduction programs has been established.
      However, the extent to which risk-reduction interventions are effective may
      depend on adherence. Non-compliance, or non-adherence, may occur with any of the
      recommended or prescribed regimens and may vary across the treatment course.
      Compliance problems, whether occurring early or late in the treatment course, are
      clinically significant, as adherence is one mediator of the clinical outcome.
      This article, which is based on a review of the empirical literature of the past
      20 years, addresses compliance across four regimens of cardiovascular risk
      reduction: pharmacological therapy, exercise, nutrition, and smoking cessation.
      The criteria for inclusion of a study in this review were: (a) focus on
      cardiovascular disease risk reduction; (b) report of a quantitative measure of
      compliance behavior; and (c) use of a randomized controlled design. Forty-six
      studies meeting these criteria were identified. A variety of self-report,
      objective, and electronic measurement methods were used across these studies. The
      interventions employed diverse combinations of cognitive, educational, and
      behavioral strategies to improve compliance in an array of settings. The
      strategies demonstrated to be successful in improving compliance included
      behavioral skill training, self-monitoring, telephone/mail contact, self-efficacy
      enhancement, and external cognitive aids. A series of tables summarize the
      intervention strategies, compliance measures, and findings, as well as the
      interventions demonstrated to be successful. This review reflects the progress
      made over two decades in compliance measurement and research and, further,
      advances made in the application of behavioral strategies to the promotion of
      cardiovascular risk reduction.

PMID- 9603700
TI  - Psychologic and social aspects of cardiovascular disease.
AB  - In summarizing the evidence, it becomes apparent that several psychologic and
      social variables are related to coronary heart disease (CHD). Coronary prone
      behavior pattern, in particular the hostility component, appears to be related to
      the development and perhaps expression of CHD, whereas it is not reliably related
      to outcomes after CHD is manifest. Depression clearly has been shown to be
      related to outcomes after CHD has declared itself. Lack of social ties appears to
      be related to mortality, whereas emotional social support has been shown to be
      related to recovery from coronary events. It also seems apparent that there are
      subsets of vulnerable individuals who might be best served by targeted
      interventions. Interventions are proposed as suggested by the prevailing
      evidence.

PMID- 9603701
TI  - Delivering clinical preventive services is a systems problem.
AB  - A steadily increasing number of research trials and prevention advocates are
      identifying the practice environment as the main source of both problems and
      solutions to the improved delivery of clinical preventive services. Although
      these sources are correctly focusing on office systems as solutions, there is a
      tendency to focus on only parts of a system and to relate this to just one or a
      few related preventive services. However, the effort required to set up and
      maintain an office system makes it difficult to justify doing so for a single
      clinical activity. The process and system thinking of Continuous Quality
      Improvement (CQI) theory suggests that there may be both efficiency and
      effectiveness advantages to the concept of all clinical preventive services being
      served by a single system with many interrelated component processes. Such a
      system should be usable for all age groups. This system and its literature base
      are described. The feasibility of applying this concept is being tested in a
      randomized controlled trial in 44 primary care clinics in Minnesota and
      Wisconsin.

PMID- 9603702
TI  - Examination of changes in interpersonal stress as a factor in disease
      exacerbations among women with rheumatoid arthritis.
AB  - OBJECTIVE: This study examined the effects of change in interpersonal stress on
      disease activity among 41 women with rheumatoid arthritis (RA). METHODS: Measures
      of everyday stressful events and perceived stress were collected weekly for
      twelve weeks and related to disease activity in a series of pooled time-series
      regression analyses. RESULTS: Increases in the number of interpersonal stressors
      in the same week and one week prior were associated with increases in disease
      activity. Pain from joint tenderness also was significantly related to a decrease
      in stressful events one week later. A subgroup of 20 patients showed a
      significant increase in interpersonal stress from baseline during the course of
      the study. For this group, significant elevations in DR + CD3 cells, sIL-2R,
      clinician's rating of disease, and self-reports of joint tenderness were found
      during the week of increased interpersonal stress. CONCLUSIONS: Interpersonal
      stress appears to be associated with increases in disease activity among RA
      patients.

PMID- 9603703
TI  - Helplessness, self-efficacy, cognitive distortions, and depression in multiple
      sclerosis and spinal cord injury.
AB  - The aim of this study was to determine if learned helplessness, self-efficacy,
      and cognitive distortions would predict depression in a sample of 80 individuals
      with multiple sclerosis (MS) and 80 individuals with a spinal cord injury (SCI).
      As MS and SCI usually present with disparate disease courses and etiologies, a
      secondary objective was to determine if individuals with MS would exhibit greater
      levels of helplessness, cognitive distortions, and depression and lower levels of
      self-efficacy than those with SCI. Results indicated that helplessness and self
      efficacy significantly predicted depression for both the MS and SCI groups after
      controlling for confounding variables. Cognitive distortions had no independent
      effect, indicating that cognitive distortions may have caused feelings of
      helplessness and low self-efficacy and, in this way, had indirect effects on
      depression. The MS group exhibited significantly greater levels of depression and
      helplessness and significantly lower levels of self-efficacy than the SCI group.
      It was hypothesized that it may have been the combination of an unpredictable
      course of disease activity and the possibility of being affected by MS in many
      different ways that produced greater feelings of depression, helplessness, and
      low self-efficacy in the MS group.

PMID- 9603704
TI  - Consensus analysis: reliability, validity, and informant accuracy in use of
      American and Mandarin Chinese pain descriptors.
AB  - A quantitative method for validating qualitative interview results and checking
      sample parameters is described and illustrated using common pain descriptions
      among a sample of Anglo-American and mandarin Chinese patients and dentists
      matched by age and gender. Assumptions were that subjects were members of a
      sociocultural group (e.g. ethnic or professional/lay) and answered questions
      independently about a monotonic domain (e.g. pain). Subjects answered 18
      true/false items derived from and selected to reflect pain perceptions consistent
      with published and unpublished interview data. Estimates of consistency in use of
      descriptors within groups, validity of description, accuracy of individuals
      compared with others in their group, and minimum required sample size were
      calculated using Cronbach's alpha, factor analysis, and Bayesian probability.
      Ethnic and professional differences within and across groups were also tested
      using multidimensional scaling (MDS) and hypothesis testing. Consensus
      (consistency of subject response by group) was .99 among Anglo-Americans and .97
      among Chinese. Mean subject accuracy was .81 for Americans and .57 for Chinese,
      indicating the need for larger numbers of Chinese to supplement each others'
      statements. However, larger numbers of subjects were recruited than actually
      required for each ethnic group at .95 confidence limits. MDS showed similarities
      in use of descriptors within ethnic groups, while there were differences (p <
      .001) between Chinese and American groups. Use of covalidating questionnaires
      that reflect results of qualitative interviews are recommended in order to
      estimate sample parameters such as intersubject agreement, individual subject
      accuracy, and minimum required sample sizes.

PMID- 9603706
TI  - Listening to women. The Audit Commission National Survey of Women's Views.

PMID- 9603705
TI  - Minority women and tobacco: implications for smoking cessation interventions.
AB  - Quitting smoking is the single most important preventive health behavior a woman
      can perform to significantly reduce her chances of morbidity and premature
      mortality. Minority women are an extremely important population to target for
      smoking cessation intervention. Rates and risk factors for cardiovascular
      diseases and cancer are markedly higher among women of certain minority groups.
      In addition, smoking prevalence rates in women of some ethnic groups are elevated
      relative to the majority population of women, and specific groups have displayed
      slower rates of decline in smoking. Furthermore, minority women tend to have less
      access and appear to be less responsive to smoking cessation programs aimed at
      the majority culture. Thus, consideration of the practical and cultural needs of
      ethnic minority women is imperative when designing smoking intervention programs.
      This article describes the smoking behaviors of African-American, American Indian
      and Native Alaskan, Asian and Pacific Islander, and Hispanic women smokers, in
      order to gain a greater understanding of the treatment needs of these women.
      Information on prevalence rates and smoking patterns, barriers to quitting, and
      findings from intervention studies within each population are reviewed as well as
      recommendations for smoking cessation treatment.

PMID- 9603707
TI  - The future of the midwifery profession.

PMID- 9603708
TI  - Effective communication: sharpening your skills.

PMID- 9603709
TI  - Minor disorder.

PMID- 9603710
TI  - Labour of love.

PMID- 9603711
TI  - The persistent OP. Can maternal position rotate the baby?

PMID- 9603712
TI  - Miscarriage.

PMID- 9603714
TI  - Report writing in midwifery.

PMID- 9603713
TI  - Vitamins and pregnancy: teenagers' beliefs.

PMID- 9603715
TI  - Sweeping the membranes.

PMID- 9603716
TI  - Rewriting the rules.

PMID- 9603717
TI  - Assertiveness. An essential tool for the midwife.

PMID- 9603718
TI  - Crossed wires.

PMID- 9603719
TI  - Environmental contributions to the obesity epidemic.
AB  - The current epidemic of obesity is caused largely by an environment that promotes
      excessive food intake and discourages physical activity. Although humans have
      evolved excellent physiological mechanisms to defend against body weight loss,
      they have only weak physiological mechanisms to defend against body weight gain
      when food is abundant. Control of portion size, consumption of a diet low in fat
      and energy density, and regular physical activity are behaviors that protect
      against obesity, but it is becoming difficult to adopt and maintain these
      behaviors in the current environment. Because obesity is difficult to treat,
      public health efforts need to be directed toward prevention.

PMID- 9603720
TI  - The search for human obesity genes.
AB  - Understanding of the genetic influences on obesity has increased at a tremendous
      rate in recent years. By some estimates, 40 to 70 percent of the variation in
      obesity-related phenotypes in humans is heritable. Although several single-gene
      mutations have been shown to cause obesity in animal models, the situation in
      humans is considerably more complex. The most common forms of human obesity arise
      from the interactions of multiple genes, environmental factors, and behavior, and
      this complex etiology makes the search for obesity genes especially challenging.
      This article discusses the strategies currently being used to search for human
      obesity genes and recent promising results from these efforts.

PMID- 9603721
TI  - Signals that regulate food intake and energy homeostasis.
AB  - Feeding behavior is critical for survival. In addition to providing all of the
      body's macronutrients (carbohydrates, lipids, and proteins) and most
      micronutrients (minerals and vitamins), feeding behavior is a fundamental aspect
      of energy homeostasis, the process by which body fuel stored in the form of
      adipose tissue is held constant over long intervals. For this process to occur,
      the amount of energy consumed must match precisely the amount of energy expended.
      This review focuses on the molecular signals that modulate food intake while
      integrating the body's immediate and long-term energy needs.

PMID- 9603722
TI  - Strategies and potential molecular targets for obesity treatment.
AB  - Obesity is an increasingly prevalent and important health problem. Although
      treatment is available, the long-term maintenance of medically significant weight
      loss (5 to 10 percent of initial body weight) is rare. Since 1995 there has been
      an explosion of research focused on the regulation of energy balance and fat
      mass. Characterization of obesity-associated gene products has revealed new
      biochemical pathways and molecular targets for pharmacological intervention that
      will likely lead to new treatments. Ideally, these treatments will be viewed as
      adjuncts to behavioral and lifestyle changes aimed at maintenance of weight loss
      and improved health.

PMID- 9603724
TI  - Extracting primordial density fluctuations 
AB  - The combination of detections of anisotropy in cosmic microwave background
      radiation and observations of the large-scale distribution of galaxies probes the
      primordial density fluctuations of the universe on spatial scales varying by
      three orders of magnitude. These data are found to be inconsistent with the
      predictions of several popular cosmological models. Agreement between the data
      and the cold + hot dark matter model, however, suggests that a significant
      fraction of the matter in the universe may consist of massive neutrinos.

PMID- 9603723
TI  - Eating disorders: progress and problems.
AB  - Recent research on Anorexia Nervosa and Bulimia Nervosa has yielded an
      increasingly detailed understanding of the range of biological and psychological
      abnormalities associated with these eating disorders. Inherited vulnerabilities,
      cultural pressures, and adverse individual and family experiences all appear to
      contribute to the onset of extreme dieting, binge eating, and purging. Once
      initiated, these behaviors give rise to multiple physiological disturbances, some
      of which may serve to perpetuate the illness. Although there have been
      substantial advances in the management of Bulimia Nervosa, the goal of offering
      effective treatment to all individuals with eating disorders remains elusive.
      This article reviews current thinking on the etiology and treatment of the two
      major eating disorders and a related syndrome, Binge Eating Disorder.

PMID- 9603725
TI  - Phase-matched generation of coherent soft X-rays 
AB  - Phase-matched harmonic conversion of visible laser light into soft x-rays was
      demonstrated. The recently developed technique of guided-wave frequency
      conversion was used to upshift light from 800 nanometers to the range from 17 to
      32 nanometers. This process increased the coherent x-ray output by factors of
      10(2) to 10(3) compared to the non-phase-matched case. This source uses a small
      scale (sub-millijoule) high repetition-rate laser and will enable a wide variety
      of new experimental investigations in linear and nonlinear x-ray science.

PMID- 9603726
TI  - Electrical conductivity of olivine, wadsleyite, and ringwoodite under upper
      mantle conditions 
AB  - Geophysical models show that electrical conductivity in Earth's mantle rises
      about two orders of magnitude through the transition zone in the depth range 410
      to 660 kilometers. Impedance measurements obtained on Mg1.8Fe0.2SiO4 olivine,
      wadsleyite, and ringwoodite at up to 20 gigapascals and 1400 degreesC show that
      the electrical conductivities of wadsleyite and ringwoodite are similar and are
      almost two orders of magnitude higher than that of olivine. A conductivity-depth
      profile to 660 kilometers, based on these laboratory data, shows a conductivity
      increase of almost two orders of magnitude across the 410-kilometer
      discontinuity; such a profile favors a two-layer model for the upper mantle.
      Activation enthalpies of 1.2 to 1.7 electron volts permit appreciable lateral
      variations of conductivity with lateral temperature variations.

PMID- 9603727
TI  - In situ discovery of graphite with interstellar isotopic signatures in a
      chondrule-free clast in an L3 chondrite 
AB  - Optical and scanning electron microscopy of a chondrule-free clast in the
      unequilibrated L3 chondrite Khohar revealed a spherical object consisting of an
      aggregate of small ( approximately 2- micrometer diameter), Ni-poor (0.5 to 2.89
      weight percent) metal particles and fine-grained graphite (<1-micrometer
      diameter). The graphite has large D and 15N excesses (deltaD approximately 1500
      per mil and delta15N approximately 1300 per mil) with two isotopically distinct
      signatures: N rich with a high D/H ratio and N poor with a high 15N/14N ratio.
      These excesses are the largest D and 15N excesses observed in situ in a well
      characterized phase in a meteorite. The isotopic characteristics are suggestive
      of an interstellar origin, probably by ion-molecule reactions at low temperature
      in the interstellar molecular cloud from which the solar system formed. The
      structure and nonchondritic composition of the metal particles suggest they did
      not form under equilibrium conditions in the solar nebula.

PMID- 9603728
TI  - Eclogitic diamond formation at jwaneng: No room for a recycled component 
AB  - Eclogitic diamonds have a large range of delta13C values, whereas peridotitic
      diamonds do not. Paired delta15N-delta13C-N variations in 40 eclogitic diamonds
      from the Jwaneng kimberlite in Botswana show that neither the influence of
      recycled biogenic carbon nor the global and primordial heterogeneity of mantle
      carbon are likely for the origin of the large delta13C range; the data instead
      support a fractionation process. It is proposed that carbonatitic mantle melts
      from which diamonds crystallize undergo different evolutions before diamond
      precipitation, when percolating through either a peridotite or an eclogite. These
      different evolutions, reflecting the presence or absence of olivine, can account
      for their respective delta13C distributions.

PMID- 9603729
TI  - Multiple-step melting in two-dimensional hexatic liquid-crystal films 
AB  - An unexpected three-stage melting transition has been observed in two-dimensional
      (2D) free-standing liquid-crystal films by in situ electron-diffraction and
      optical-reflectivity measurements. These data suggest the existence of two phases
      between the 2D solid and liquid: a hexatic phase and, at a higher temperature, an
      intermediate liquid phase with hexatic-like positional correlations (
      approximately 40 angstroms) but no long-range orientational order. Previous high
      resolution heat-capacity measurements have revealed a divergent-like anomaly at
      the hexatic-liquid transition that sharply contradicts the predictions of 2D
      melting theories. The observation of an intermediate isotropic phase may alter
      our understanding of 2D melting and lead to reconciliation between current
      experiments and theories.

PMID- 9603730
TI  - Helical superstructures from charged Poly(styrene)-Poly(isocyanodipeptide) block
      copolymers 
AB  - Amphiphilic block copolymers containing a poly(styrene) tail and a charged
      helical poly(isocyanide) headgroup derived from isocyano-L-alanine-L-alanine and
      isocyano-L-alanine-L-histidine were prepared. Analogous to low-molecular mass
      surfactants, these block copolymers self-assembled in aqueous systems to form
      micelles, vesicles, and bilayer aggregates. The morphology of these aggregates
      can be controlled by variation of the length of the poly(isocyanide) block, the
      pH, and the anion-headgroup interactions. The chirality of the macromolecules
      results in the formation of helical superstructures that have a helical sense
      opposite to that of the constituent block copolymers. The great variety of
      morphologies displayed by these block copolymers and the fact that they are
      easily accessible from poly(styrene) and different types of peptides open new
      opportunities for applications in the fields of life and materials sciences.

PMID- 9603731
TI  - Identification of water ice on the Centaur 1997 CU26.
AB  - Spectra of the Centaur 1997 CU26 were obtained at the Keck Observatory on 27
      October 1997 (universal time). The data show strong absorptions at 1.52 and 2.03
      micrometers attributable to water ice on the surface of 1997 CU26. The
      reflectance spectrum of 1997 CU26 is matched by the spectrum of a mixture of low
      temperature, particulate water ice and spectrally featureless but otherwise red
      colored material. Water ice dominates the spectrum of 1997 CU26, whereas methane
      or methane-like hydrocarbons apparently dominate the spectrum of the Kuiper belt
      object 1993 SC, perhaps indicating different origins, thermal histories, or both
      for these two objects.

PMID- 9603732
TI  - Impairment of mycobacterial immunity in human interleukin-12 receptor deficiency.
AB  - In humans, interferon gamma (IFN-gamma) receptor deficiency leads to a
      predisposition to mycobacterial infections and impairs the formation of mature
      granulomas. Interleukin-12 (IL-12) receptor deficiency was found in otherwise
      healthy individuals with mycobacterial infections. Mature granulomas were seen,
      surrounded by T cells and centered with epithelioid and multinucleated giant
      cells, yet reduced IFN-gamma concentrations were found to be secreted by
      activated natural killer and T cells. Thus, IL-12-dependent IFN-gamma secretion
      in humans seems essential in the control of mycobacterial infections, despite the
      formation of mature granulomas due to IL-12-independent IFN-gamma secretion.

PMID- 9603733
TI  - Severe mycobacterial and Salmonella infections in interleukin-12 receptor
      deficient patients.
AB  - Interleukin-12 (IL-12) is a cytokine that promotes cell-mediated immunity to
      intracellular pathogens by inducing type 1 helper T cell (TH1) responses and
      interferon-gamma (IFN-gamma) production. IL-12 binds to high-affinity beta1/beta2
      heterodimeric IL-12 receptor (IL-12R) complexes on T cell and natural killer
      cells. Three unrelated individuals with severe, idiopathic mycobacterial and
      Salmonella infections were found to lack IL-12Rbeta1 chain expression. Their
      cells were deficient in IL-12R signaling and IFN-gamma production, and their
      remaining T cell responses were independent of endogenous IL-12. IL-12Rbeta1
      sequence analysis revealed genetic mutations that resulted in premature stop
      codons in the extracellular domain. The lack of IL-12Rbeta1 expression results in
      a human immunodeficiency and shows the essential role of IL-12 in resistance to
      infections due to intracellular bacteria.

PMID- 9603734
TI  - Optimizing sound features for cortical neurons.
AB  - The brain's cerebral cortex decomposes visual images into information about
      oriented edges, direction and velocity information, and color. How does the
      cortex decompose perceived sounds? A reverse correlation technique demonstrates
      that neurons in the primary auditory cortex of the awake primate have complex
      patterns of sound-feature selectivity that indicate sensitivity to stimulus edges
      in frequency or in time, stimulus transitions in frequency or intensity, and
      feature conjunctions. This allows the creation of classes of stimuli matched to
      the processing characteristics of auditory cortical neurons. Stimuli designed for
      a particular neuron's preferred feature pattern can drive that neuron with higher
      sustained firing rates than have typically been recorded with simple stimuli.
      These data suggest that the cortex decomposes an auditory scene into component
      parts using a feature-processing system reminiscent of that used for the cortical
      decomposition of visual images.

PMID- 9603735
TI  - Correction of deafness in shaker-2 mice by an unconventional myosin in a BAC
      transgene.
AB  - The shaker-2 mouse mutation, the homolog of human DFNB3, causes deafness and
      circling behavior. A bacterial artificial chromosome (BAC) transgene from the
      shaker-2 critical region corrected the vestibular defects, deafness, and inner
      ear morphology of shaker-2 mice. An unconventional myosin gene, Myo15, was
      discovered by DNA sequencing of this BAC. Shaker-2 mice were found to have an
      amino acid substitution at a highly conserved position within the motor domain of
      this myosin. Auditory hair cells of shaker-2 mice have very short stereocilia and
      a long actin-containing protrusion extending from their basal end. This
      histopathology suggests that Myo15 is necessary for actin organization in the
      hair cells of the cochlea.

PMID- 9603736
TI  - Association of unconventional myosin MYO15 mutations with human nonsyndromic
      deafness DFNB3.
AB  - DFNB3, a locus for nonsyndromic sensorineural recessive deafness, maps to a 3
      centimorgan interval on human chromosome 17p11.2, a region that shows conserved
      synteny with mouse shaker-2. A human unconventional myosin gene, MYO15, was
      identified by combining functional and positional cloning approaches in searching
      for shaker-2 and DFNB3. MYO15 has at least 50 exons spanning 36 kilobases.
      Sequence analyses of these exons in affected individuals from three unrelated
      DFNB3 families revealed two missense mutations and one nonsense mutation that
      cosegregated with congenital recessive deafness.

PMID- 9603737
TI  - Continuity in evolution: on the nature of transitions.
AB  - To distinguish continuous from discontinuous evolutionary change, a relation of
      nearness between phenotypes is needed. Such a relation is based on the
      probability of one phenotype being accessible from another through changes in the
      genotype. This nearness relation is exemplified by calculating the shape
      neighborhood of a transfer RNA secondary structure and provides a
      characterization of discontinuous shape transformations in RNA. The simulation of
      replicating and mutating RNA populations under selection shows that sudden
      adaptive progress coincides mostly, but not always, with discontinuous shape
      transformations. The nature of these transformations illuminates the key role of
      neutral genetic drift in their realization.

PMID- 9603738
TI  - Noggin, cartilage morphogenesis, and joint formation in the mammalian skeleton.
AB  - Noggin is a bone morphogenetic protein (BMP) antagonist expressed in Spemann's
      organizer. Murine Noggin is expressed in condensing cartilage and immature
      chondrocytes, as are many BMPs. In mice lacking Noggin, cartilage condensations
      initiated normally but developed hyperplasia, and initiation of joint development
      failed as measured by the expression of growth and differentiation factor-5. The
      maturation of cartilage and Hoxd expression were unaffected. Excess BMP activity
      in the absence of Noggin antagonism may enhance the recruitment of cells into
      cartilage, resulting in oversized growth plates; chondrocytes are also refractory
      to joint-inducing positional cues.

PMID- 9603739
TI  - Professional and practice development plans for primary care teams. Life after
      the postgraduate education allowance.

PMID- 9603740
TI  - The health of adult Europe. Combating inequalities involves measuring what
      counts.

PMID- 9603741
TI  - Applying research evidence to individual patients. Evidence based case reports
      will help.

PMID- 9603742
TI  - Renegotiating medicine's contract with patients. The GMC is leading the way.

PMID- 9603743
TI  - Medical ethics and law as a core subject in medical education. A core curriculum
      offers flexibility in how it is taught-but not that it is taught.

PMID- 9603744
TI  - Adverse socioeconomic conditions in childhood and cause specific adult mortality:
      prospective observational study.
AB  - OBJECTIVE: To investigate the association between social circumstances in
      childhood and mortality from various causes of death in adulthood. DESIGN:
      Prospective observational study. SETTING: 27 workplaces in the west of Scotland.
      SUBJECTS: 5645 men aged 35-64 years at the time of examination. MAIN OUTCOME
      MEASURES: Death from various causes. RESULTS: Men whose fathers had manual
      occupations when they were children were more likely as adults to have manual
      jobs and be living in deprived areas. Gradients in mortality from coronary heart
      disease, stroke, lung cancer, stomach cancer, and respiratory disease were seen
      (all P<0.05), generally increasing from men whose fathers had professional and
      managerial occupations (social class I and II) to those whose fathers had
      semiskilled and unskilled manual occupations (social class IV and V). Relative
      rates of mortality adjusted for age for men with fathers in manual versus non
      manual occupations were 1.52 (95% confidence interval 1.24 to 1.87) for coronary
      heart disease, 1.83 (1.13 to 2. 94) for stroke, 1.65 (1.12 to 2.43) for lung
      cancer, 2.06 (0.93 to 4. 57) for stomach cancer, and 2.01 (1.17 to 3.48) for
      respiratory disease. Mortality from other cancers and accidental and violent
      death showed no association with fathers' social class. Adjustment for adult
      socioeconomic circumstances and risk factors did not alter results for mortality
      from stroke and stomach cancer, attenuated the increased risk of coronary heart
      disease and respiratory disease, and essentially eliminated the association with
      lung cancer. CONCLUSIONS: Adverse socioeconomic circumstances in childhood have a
      specific influence on mortality from stroke and stomach cancer in adulthood,
      which is not due to the continuity of social disadvantage throughout life.
      Deprivation in childhood influences risk of mortality from coronary heart disease
      and respiratory disease in adulthood, although an additive influence of adulthood
      circumstances is seen in these cases. Mortality from lung cancer, other cancer,
      and accidents and violence is predominantly influenced by risk factors that are
      related to social circumstances in adulthood.

PMID- 9603745
TI  - Occupational class and cause specific mortality in middle aged men in 11 European
      countries: comparison of population based studies. EU Working Group on
      Socioeconomic Inequalities in Health.
AB  - OBJECTIVES: To compare countries in western Europe with respect to class
      differences in mortality from specific causes of death and to assess the
      contributions these causes make to class differences in total mortality. DESIGN:
      Comparison of cause of death in manual and non-manual classes, using data on
      mortality from national studies. SETTING: Eleven western European countries in
      the period 1980-9. SUBJECTS: Men aged 45-59 years at death. RESULTS: A north
      south gradient was observed: mortality from ischaemic heart disease was strongly
      related to occupational class in England and Wales, Ireland, Finland, Sweden,
      Norway, and Denmark, but not in France, Switzerland, and Mediterranean countries.
      In the latter countries, cancers other than lung cancer and gastrointestinal
      diseases made a large contribution to class differences in total mortality.
      Inequalities in lung cancer, cerebrovascular disease, and external causes of
      death also varied greatly between countries. CONCLUSIONS: These variations in
      cause specific mortality indicate large differences between countries in the
      contribution that disease specific risk factors like smoking and alcohol
      consumption make to socioeconomic inequalities in mortality. The mortality
      advantage of people in higher occupational classes is independent of the precise
      diseases and risk factors involved.

PMID- 9603746
TI  - Prevalence of serious eye disease and visual impairment in a north London
      population: population based, cross sectional study.
AB  - OBJECTIVE: To estimate the magnitude of serious eye disorders and of visual
      impairment in a defined elderly population of a typical metropolitan area in
      England, and to assess the frequency they were in touch with, or known to, the
      eye care services. DESIGN: Cross sectional survey using two stage cluster random
      sampling. SETTING: General practices in north London. SUBJECTS: Random sample of
      people aged 65 and older, drawn from a defined population of elderly people
      registered with 17 general practice groups. MAIN OUTCOME MEASURES: Proportions
      and population prevalence estimates were determined for visual acuity, assessed
      with the person's own spectacles (if any), classified into four categories:
      prevalence of cataract, age related macular degeneration, and refractive error
      causing visual impairment and of definite primary open angle glaucoma; and status
      of contact with eye services. RESULTS: 1547 of 1840 (84%) eligible people were
      examined. The population prevalence of bilateral visual impairment (visual acuity
      <6/12) was 30%, of which 72% was potentially remediable. 92 of these 448 cases
      (21%) had visual acuity <6/60 ("blindness") in one or both eyes. Prevalence of
      cataract causing visual impairment was 30%; 88% of these people were not in touch
      with the eye services. The prevalence of vision impairing, age related macular
      degeneration was 8% and of glaucoma (definite cases) was 3%. Three quarters of
      the people with definite glaucoma were not known to the eye services.
      CONCLUSIONS: Untreated visual impairment and eye disorders affect a substantial
      proportion of people aged 65 years and older. These findings should contribute to
      the setting up of future strategies for preservation of sight and eye health
      services in general.

PMID- 9603747
TI  - Following up outpatients by telephone: pilot study.

PMID- 9603749
TI  - Alternative definitions 

PMID- 9603748
TI  - Varying efficacy of Helicobacter pylori eradication regimens: cost effectiveness
      study using a decision analysis model.
AB  - OBJECTIVE: To determine how small differences in the efficacy and cost of two
      antibiotic regimens to eradicate Helicobacter pylori can affect the overall cost
      effectiveness of H pylori eradication in duodenal ulcer disease. DESIGN: A
      decision analysis to examine the cost effectiveness of eight H pylori eradication
      strategies for duodenal ulcer disease with and without 13C-urea breath testing to
      confirm eradication. MAIN OUTCOME MEASURES: Cumulative direct treatment costs per
      100 patients with duodenal ulcer disease who were positive for H pylori. RESULTS:
      In model 1 the strategy of omeprazole, clarithromycin, and metronidazole alone
      was the most cost effective of the four strategies assessed. The addition of the
      13C-urea breath test and a second course of omeprazole, clarithromycin, and
      metronidazole achieved the highest eradication rate (97%) but was the most
      expensive (62.63 pounds per patient). The cost of each additional effective
      eradication was 589.00 pounds (incremental cost per case) when compared with the
      cost of treating once only with omeprazole, clarithromycin, and metronidazole;
      equivalent to the cost of a patient receiving ranitidine for duodenal ulcer
      relapse for more than 15 years. Eradication strategies of omeprazole,
      amoxycillin, and metronidazole were less cost effective than omeprazole,
      clarithromycin, and metronidazole alone. In model 2 the addition of the 13C-urea
      breath test after treatment, and maintenance treatment, increased the cost of all
      the strategies and reduced the cost advantage of omeprazole, clarithromycin, and
      metronidazole alone. CONCLUSION: Small differences in efficacy can influence the
      comparative cost effectiveness of strategies for eradicating H pylori. Of the
      strategies tested the most cost effective (omeprazole, clarithromycin, and
      metronidazole alone) was neither the least expensive (omeprazole, amoxycillin,
      and metronidazole alone) nor the most effective (omeprazole, clarithromycin, and
      metronidazole with further treatment for patients found positive for H pylori on
      13C-urea breath testing). Cost effectiveness should be an important part of
      choosing an eradication strategy for H pylori.

PMID- 9603750
TI  - The anatomy of a clinical information system.

PMID- 9603752
TI  - Netlines 

PMID- 9603751
TI  - Doing as they are told 

PMID- 9603753
TI  - Twenty year cough in a non-smoker.

PMID- 9603754
TI  - Scurvy in patients with cancer.

PMID- 9603755
TI  - The new NHS: safeguards secured 

PMID- 9603756
TI  - Economic evaluation in health: a thumb nail sketch.

PMID- 9603757
TI  - Matching demand and supply fairly and efficiently.

PMID- 9603758
TI  - Health needs assessment. Whose priorities? Listening to users and the public.

PMID- 9603759
TI  - Data support extended use of levonorgestrel intrauterine systems.

PMID- 9603760
TI  - Are sex and death related? Study failed to adjust for an important confounder.

PMID- 9603761
TI  - Cancer in the offspring of radiation workers. Connection between leukaemia and
      radiation needs to be considered.

PMID- 9603762
TI  - Cognitive impairment and survival in very elderly people. Mini-mental state
      examination may not test cognitive function adequately.

PMID- 9603763
TI  - Medical students may not like statistics, but as doctors they will 

PMID- 9603764
TI  - Effect of moderate alcohol consumption on lp(a) lipoprotein concentrations.
      Reduction is supported by other studies.

PMID- 9603765
TI  - Information "Nuggets" are not easy to find quickly.

PMID- 9603766
TI  - Interventions to treat shoulder pain. Review was overly negative.

PMID- 9603768
TI  - Sir francis avery jones 

PMID- 9603767
TI  - Suspension of consultant raises serious issues.

PMID- 9603769
TI  - GMC starts consultation on SHO training 

PMID- 9603770
TI  - What kind of memory? 

PMID- 9603771
TI  - Papa, nicole, and the guideline industry 

PMID- 9603773
TI  - Dispelling the myths about addiction: strategies to increase understanding and
      strengthen research 

PMID- 9603772
TI  - Fear of tuberculosis 

PMID- 9603775
TI  - Effect of lifetime socioeconomic position on mortality varies with cause of death

PMID- 9603774
TI  - Shell-shock: A history of the changing attitude to war neurosis 

PMID- 9603777
TI  - Untreated visual impairment is common in elderly people 

PMID- 9603776
TI  - Socioeconomic inequalities for specific diseases show north-south gradient in
      europe 

PMID- 9603778
TI  - Cost effectiveness should count in choosing a strategy for eradicating
      helicobacter pylori 

PMID- 9603779
TI  - Clinical information system based on the individual patient 

PMID- 9603780
TI  - Ribonuclease-gold labels heparin in human mast cell granules. New use for an
      ultrastructural enzyme affinity technique.
AB  - We evaluated an enzyme affinity-gold ultrastructural technique designed to
      identify RNA-rich structures, based on an RNase-gold (R-G) probe in human mast
      cells (HMCs). As expected, the R-G technique labeled RNA-containing ribosomes and
      nucleoli in HMCs. The heparin-rich secretory granules in HMCs were also labeled.
      Extensive studies revealed that HMCs isolated from lung or skin and sustained in
      short-term cultures, derived de novo in growth factor-supplemented cord blood
      cell cultures, or present in vivo in multiple sites all shared this property. We
      performed a large number of controls designed to examine the HMC granule binding
      characteristics of gold alone, of irrelevant protein- or enzyme-gold reagents, of
      the role of charge and enzyme activity after various enzyme digestions, after
      blocking with macromolecules, after exposure to inhibitors of RNase, of heparin,
      or to irrelevant enzyme inhibitors, including staining of macromolecule
      containing test agar blocks and a variety of combined absorption and digestion
      experiments of the binding of R-G to HMC granules. These studies established that
      the R-G method detected heparin in this site in conventionally prepared, well
      preserved electron microscopic samples. These findings demonstrate a new use for
      this enzyme affinity-gold technique in mast cell biology, based on the known
      property of heparin as an inhibitor of RNase.

PMID- 9603781
TI  - Rat endocrine pancreatic development in relation to two homeobox gene products
      (Pdx-1 and Nkx 6.1).
AB  - We studied the distribution of the homeodomain proteins Pdx-1 and Nkx 6.1 in the
      developing rat pancreas. During early development, nuclear staining for both Pdx
      1 and Nkx 6.1 occurred in most epithelial cells of the pancreatic anlage.
      Subsequently, Nkx 6.1 became more beta-cell-restricted, and Pdx-1 also occurred
      in other islet cell types and in the duodenal epithelium. During early pancreatic
      development, cells co-storing insulin and glucagon were regularly detected. The
      vast majority of these did not possess nuclear staining for either Pdx-1 or Nkx
      6.1. Subsequently, cells storing insulin only appeared. Such cells displayed
      strongly Pdx-1- and Nkx 6.1-positive nuclei. Therefore, Nkx 6.1, like Pdx-1, may
      be an important factor in pancreatic development and in mature insulin cell
      function.

PMID- 9603782
TI  - Homeobox gene product Nkx 6.1 immunoreactivity in nuclei of endocrine cells of
      rat and mouse stomach.
AB  - The homeobox gene product Nkx 6.1 is of unknown function but is expressed in the
      pancreas and the antropyloric mucosa of the stomach. In the adult pancreas, Nkx
      6.1 possesses an insulin cell-restricted distribution, whereas its localization
      in the stomach is unknown. We now show that the vast majority of serotonin
      producing enterochromaffin cells of the antropyloric mucosa contain Nkx 6. 1
      immunoreactive nuclei. In addition, a subpopulation of cells co-storing serotonin
      and gastrin display Nkx 6.1-positive nuclei. Such cells have been postulated to
      represent precursors of mature gastrin and serotonin cells. The nuclei of the co
      storing cells have previously also been found to be positive for another
      homeodomain protein, Pdx-1. Pdx-1-deficient animals were therefore investigated
      and were found to be devoid of Nkx 6.1-positive nuclei. Our data show that Pdx-1
      is needed for Nkx 6.1 expression and suggest a role for Nkx 6.1 in the maturation
      of gastrin- and serotonin-positive precursor cells.

PMID- 9603783
TI  - ADAM-10 message is expressed in human articular cartilage.
AB  - The depletion of the pericellular and territorial matrices in articular cartilage
      is considered to be one of the earliest events in pathobiology of osteoarthritis
      (OA). A newly discovered family of proteins with a disintegrin-like and
      metalloproteinase-like domain (ADAM) may be involved in matrix degradation as
      well as in cell-cell and cell-matrix interactions. The purpose of this study was
      to determine by in situ hybridization whether human articular chondrocytes from
      newborn, normal adult, and OA cartilages express messenger RNA for ADAM-10, one
      of the members of this family, and by semiquantitative RT-PCR to compare the
      levels of this expression. The results confirmed the expression of ADAM-10 by
      human articular chondrocytes and revealed the highest levels of expression in the
      continuously remodeling cartilage of newborns and the most fibrillated areas of
      OA cartilage, especially the regions of cell clusters. Importantly, ADAM-10 mRNA
      expression was evident in tissues with the greatest loss of Safranin O staining
      from the territorial and interterritorial matrix of the chondrocytes. Messenger
      RNA was upregulated in OA tissue compared to the age-matched normal cartilage, as
      detected by RT-PCR. Upregulated levels of ADAM-10 mRNA expression appear to be
      related to the degree of cartilage damage and/or degradation, which suggests a
      potential role for at least one member of this new family in the cartilage matrix
      destruction accompanying OA.

PMID- 9603784
TI  - Cytochemical demonstration of oxidative damage in Alzheimer disease by
      immunochemical enhancement of the carbonyl reaction with 2,4
      dinitrophenylhydrazine.
AB  - Formation of carbonyls derived from lipids, proteins, carbohydrates, and nucleic
      acids is common during oxidative stress. For example, metal-catalyzed, "site
      specific" oxidation of several amino acid side-chains produces aldehydes or
      ketones, and peroxidation of lipids generates reactive aldehydes such as
      malondialdehyde and hydroxynonenal. Here, using in situ 2,4
      dinitrophenylhydrazine labeling linked to an antibody system, we describe a
      highly sensitive and specific cytochemical technique to specifically localize
      biomacromolecule-bound carbonyl reactivity. When this technique was applied to
      tissues from cases of Alzheimer disease, in which oxidative events including
      lipoperoxidative, glycoxidative, and other oxidative protein modifications have
      been reported, we detected free carbonyls not only in the disease-related
      intraneuronal lesions but also in other neurons. In marked contrast, free
      carbonyls were not found in neurons or glia in age-matched control cases.
      Importantly, this assay was highly specific for detecting disease-related
      oxidative damage because the site of oxidative damage can be assessed in the
      midst of concurrent age-related increases in free carbonyls in vascular basement
      membrane that would contaminate biochemical samples subjected to bulk analysis.
      These findings demonstrate that oxidative imbalance and stress are key elements
      in the pathogenesis of Alzheimer disease.

PMID- 9603785
TI  - Placental lactogen-I (PL-I) target tissues identified with an alkaline
      phosphatase-PL-I fusion protein.
AB  - The rat placenta expresses a family of genes related to prolactin (PRL). Target
      tissues and physiological roles for many members of the PRL family have yet to be
      determined. In this investigation we evaluated the use of an alkaline phosphatase
      (AP) tag for monitoring the behavior of a prototypical member of the PRL family,
      placental lactogen-I (PL-I). A probe was generated consisting of a fusion protein
      of human placental AP and rat PL-I (AP-PL-I). The AP-PL-I construct was stably
      expressed in 293 human fetal kidney cells, as was the unmodified AP vector that
      served as a control. AP activity was monitored with a colorimetric assay in
      conditioned medium from transfected cells. Immunoreactivity and PRL-like
      biological activities of the AP-PL-I fusion protein were demonstrated by
      immunoblotting and the Nb2 lymphoma cell proliferation assay, respectively. AP-PL
      I specifically bound to tissue sections known to express the PRL receptor,
      including the ovary, liver, and choroid plexus. Binding of AP-PL-I to tissues was
      specific and could be competed with ovine PRL. The results indicate that AP is an
      effective tag for monitoring the behavior of PL-I and suggest that this labeling
      system may also be useful for monitoring the actions of other members of the PRL
      family.

PMID- 9603786
TI  - Differential localization of cysteine protease inhibitors and a target cysteine
      protease, cathepsin B, by immuno-confocal microscopy.
AB  - The cystatin superfamily of cysteine protease inhibitors and target cysteine
      proteases such as cathepsin B have been implicated in malignant progression. The
      respective cellular/extracellular localization of cystatins and cysteine
      proteases in tumors may be critical in regulating activity of the enzymes.
      Confocal microscopy has enabled us to demonstrate the differential localization
      of cystatins and cathepsin B in an embryonic liver cell line and an invasive
      hepatoma cell line. In both, stefins A and B were distributed diffusely
      throughout the cytoplasm, whereas cystatin C was distributed in juxtanuclear
      vesicles. Stefin A and cystatin C, but not stefin B, were present on the cell
      surface. Cystatin C was found on the top surfaces of both cell lines, whereas
      stefin A was found only on the top surface of the embryonic liver cells.
      Cathepsin B staining was concentrated in perinuclear vesicles in the embryonic
      liver cells. In the hepatoma cells, staining for cathepsin B was also present in
      vesicles adjacent to the cell membrane and on localized regions of the bottom
      surface. Such a disparate distribution of cathepsin B and its endogenous
      inhibitors may facilitate proteolysis by the hepatoma cells and thereby
      contribute to their invasive phenotype.

PMID- 9603787
TI  - An in situ hybridization histochemistry technique allowing simultaneous
      visualization by the use of confocal microscopy of three cellular mRNA species in
      individual neurons.
AB  - We present a specific and sensitive method for simultaneous detection of three
      mRNA species in individual neurons. The method relies on the use of riboprobes
      labeled with [35S]-UTP, digoxigenin-UTP, or biotin-UTP. The nonradioactive probes
      were sequentially revealed by incubation with anti-digoxigenin immunoglobulins or
      streptavidin conjugated to peroxidase, followed by the use of fluorochrome
      labeled tyramides as peroxidase substrates. The radioactive probe was revealed by
      conventional autoradiography. There was no interaction among the different probes
      or the various detection systems. We demonstrate the use of this method by
      illustrating on laser scanning confocal microscopy the co-localization of the
      mRNAs coding for corticotropin-releasing factor (CRF), arginine vasopressin
      (AVP), or peptidylglycine alpha-amidating monooxygenase (PAM) in rat hypothalamic
      paraventricular nucleus (PVN) and its modulation by endogenous glucocorticoids.
      Our results suggest that this method could be used not only to study the
      regulation of the hypothalamo-pituitary-adrenal axis but also in various models
      in which mRNAs are present at low concentrations.

PMID- 9603788
TI  - Flow cytometric assay of cytochemically demonstrated NAD(P)H oxidoreductase
      (diaphorase) activities.
AB  - The tetrazolium salt 5-cyano-2,3-di-p-toluyl-tetrazolium chloride (CTC), yielding
      a fluorescent formazan on reduction, was used to measure NAD(P)H oxidoreductase
      activity. In this study, optimal conditions for the flow cytometric technique
      were determined empirically with tissue culture cell lines and mouse Ehrlich
      ascites cells. Applying a coupled reaction procedure, NADH and NADPH as
      substrates of the oxidoreductases to be measured are generated endogenously by
      lactate or glucose-6-phosphate dehydrogenase, respectively. The results were
      evaluated by combining spectrophotometry and flow cytometry. We obtained integral
      activities for each group of NADH and NADPH oxidoreductases. Furthermore, by
      counterstaining the DNA with DAPI, followed by bivariate analysis of flow
      cytometric data, our assay gives a detailed distribution of enzyme activities of
      all cells, even in subgroups present in heterogeneous cell populations.
      Therefore, this protocol permits the study of NAD(P)H oxidoreductase activities
      in ex vivo tumor samples in which mixed cellular populations may be present.

PMID- 9603789
TI  - A histochemical approach to correlative light and electron microscopic detection
      of acidic glycoconjugates by a sensitized high iron diamine method.
AB  - A sensitized high iron diamine method is among the reliable and useful
      histochemical means of detecting acidic glycoconjugates by light microscopy.
      Because the final reaction products obtained using this method are heavy metals,
      it can be applied to specimens for visualization by both light and electron
      microscopy. In this study the high iron diamine method was utilized successfully
      as a correlative light and electron microscopic method for detection of acidic
      glycoconjugates.

PMID- 9603791
TI  - Staining of the midbody by an anti-digoxin-specific antibody.
AB  - Using RNA in situ hybridization to reveal cytoplasmic localization patterns of
      mRNAs in cultured cells, we noted unexpected staining of a cytoplasmic component
      in telophase cells. Control experiments revealed that the anti-digoxin-specific
      antibody was responsible for this staining. Because the staining was observed
      only at a position where both daughter cells are still connected, we identified
      the stained component as the midbody. This was confirmed by double staining of
      cells with anti-digoxin and anti-alpha-tubulin antibodies. We concluded that anti
      digoxin-specific antibody shows crossreactivity with a component present in the
      midbody.

PMID- 9603790
TI  - Rapid synthesis of biotin-, digoxigenin-, trinitrophenyl-, and fluorochrome
      labeled tyramides and their application for In situ hybridization using CARD
      amplification.
AB  - A one-step procedure for the synthesis of different tyramide conjugates, which
      can be utilized in the catalyzed reporter deposition (CARD) amplification system,
      is described. Succinimidyl esters of biotin, digoxigenin, and of the
      fluorochromes fluorescein, rhodamine, aminomethylcoumarine acetic acid, and Cy3
      were coupled to tyramine in dimethylformamide (DMF) adjusted to a pH of 7.0-8.0
      with triethylamine (TEA). The coupling reaction can be performed within 2 hr and
      the reaction mixture can be applied without further purification steps.
      Furthermore, trinitrophenyl (TNP)-tyramide was prepared by adding 2,4,6,
      trinitrobenzenesulfonic acid to tyramine dissolved in either MilliQ/DMF basified
      with TEA or in an NaHCO3 (pH 9.5) buffer. A subsequent precipitation of the TNP
      tyramide resulted in a high-yield isolation of this conjugate. The synthesized
      tyramide conjugates were applied successfully in single- and multiple-target in
      situ hybridization (ISH) procedures to detect both repetitive and single-copy DNA
      target sequences in cell preparations with high efficiency. The described
      approach provides an easy and fast method to prepare a variety of tyramide
      conjugates in bulk amounts at relatively low cost.

PMID- 9603792
TI  - Localization of apoptotic cells in the human epidermis by an in situ DNA nick end
      labeling method using confocal reflectant laser microscopy.
AB  - We describe an immunohistochemical method that allows the detection of apoptotic
      cells in human epidermis by use of confocal laser reflectance and antibody
      immunogold-silver complexes. For this purpose, the site of free 3'-OH DNA ends
      was detected by the reflectance from heavy metal products (anti-digoxigenin
      antibody-immunogold-silver complexes) instead of 3, 3'-diaminobenzidine (DAB)
      reaction products in the conventional in situ nick end-labeling of DNA strand
      breaks (ISEL) technique. Localization of double-stranded DNA was demonstrated by
      the autofluorescence of methyl green. The ISEL technique using confocal
      reflectant laser microscopy (CRLM) clearly showed the most intense reflectance in
      the nuclei of granular cells, in contrast to only a weaker reflectance in those
      of basal cells. On the other hand, the extent of autofluorescence of methyl green
      was significantly more intense in the nuclei of basal cells and showed a
      reciprocal relation to that of the reflectance. Therefore, granular cells were
      most prone to apoptosis and did not contain double-stranded DNA, as indicated by
      the lack of stainability with methyl green. In addition, this method
      demonstrating the simultaneous localization of both free 3'-OH DNA ends and
      double-stranded DNA proved to have a wide range of applications, including the
      study of other DNA autolytic processes.

PMID- 9603793
TI  - Nonoccupational exposure to chrysotile asbestos and the risk of lung cancer.
AB  - BACKGROUND: Heavy industrial exposure to asbestos causes lung cancer and
      mesothelioma, but it remains unknown whether much lower environmental exposure to
      asbestos also causes these cancers. Nevertheless, regulatory agencies, including
      the Environmental Protection Agency (EPA), have assessed the risk of lung cancer
      by extrapolating known risks from past industrial exposure to asbestos to today's
      much lower environmental asbestos levels (roughly 100,000 times lower). We also
      tested the EPA's model for predicting the risk of asbestos-induced lung cancer in
      a population of women with relatively high levels of nonoccupational exposure to
      asbestos. METHODS: Mortality among women in 2 chrysotile-asbestos-mining areas of
      the province of Quebec was compared with mortality among women in 60 control
      areas, and age-standardized mortality ratios were derived. With the help of an
      expert panel, we estimated past exposure to asbestos among women in the mining
      areas and used these data with the EPA's model to predict the relative risk of
      lung cancer. We then compared this prediction with the observed mortality ratios.
      RESULTS: On the basis of the estimated exposure in the asbestos-mining areas, a
      relative risk of death due to lung cancer of 2.1 was predicted by the EPA's
      model, amounting to about 75 excess deaths from lung cancer in this population.
      By contrast, we calculated a standardized mortality ratio of 1.0 and a
      standardized proportionate mortality ratio of 1.1 (P> 0.05), suggesting that
      there were between 0 and 6.5 excess deaths from lung cancer among the women with
      nonoccupational exposure to asbestos. Seven deaths from pleural cancer were
      observed (relative risk=7.63; P<0.05). CONCLUSIONS: We found no measurable excess
      risk of death due to lung cancer among women in two chrysotile-asbestos-mining
      regions. The EPA's model overestimated the risk of asbestos-induced lung cancer
      by at least a factor of 10.

PMID- 9603794
TI  - Lack of efficacy of light reduction in preventing retinopathy of prematurity.
      Light Reduction in Retinopathy of Prematurity (LIGHT-ROP) Cooperative Group.
AB  - BACKGROUND: Hospital-nursery lighting has been suggested as a factor in causing
      retinopathy of prematurity. Despite ongoing debate, a causal relation has not
      been established. METHODS: We conducted a prospective, randomized, multicenter
      study of the effects of light reduction on 409 premature infants with birth
      weights of less than 1251 g and gestational ages of less than 31 weeks. Two
      hundred five infants were exposed to reduced light, and 204 to typical nursery
      lighting. The amount of light reaching the infants' eyes was reduced within 24
      hours after birth by placing goggles on the infants that reduced visible-light
      exposure by 97 percent and ultraviolet-light exposure by 100 percent. The babies
      wore the goggles until 31 weeks' postconceptional age or 4 weeks after birth,
      whichever was longer. Once the goggles were removed, ophthalmologists masked to
      the treatment assignments assessed the infants for retinopathy of prematurity at
      least biweekly for up to 13 weeks. RESULTS: There were 188 infants in the group
      that wore goggles and 173 in the control group who survived and were available
      for follow-up. The mean birth weights were 906 g in the goggles group and 914 g
      in the control group; the mean gestational ages were 27.4 weeks and 27.2 weeks,
      respectively. The mean ambient-light level adjacent to the infants' faces was 399
      lux for the goggles group and 447 lux for the control group. Retinopathy of
      prematurity was diagnosed in 102 infants (54 percent) in the goggles group and
      100 (58 percent) in the control group (relative risk, 0.9; 95 percent confidence
      interval, 0.8 to 1.1; P=0.50). CONCLUSIONS: A reduction in ambient-light exposure
      does not alter the incidence of retinopathy of prematurity.

PMID- 9603795
TI  - Association of mutations in the apolipoprotein B gene with hypercholesterolemia
      and the risk of ischemic heart disease.
AB  - BACKGROUND: Familial hypercholesterolemia leads to premature ischemic heart
      disease and is often caused by mutations in the gene for the low-density
      lipoprotein receptor. Mutations in the apolipoprotein B gene, which encodes a
      ligand for this receptor, may also result in this phenotype. METHODS: We studied
      the genotypes of 9255 women and men from the general population, 948 patients
      with ischemic heart disease, and 36 patients with familial hypercholesterolemia,
      all from Denmark, for three mutations in the apolipoprotein B gene: Arg3500Gln,
      Arg3531Cys, and Arg3500Trp. RESULTS: The prevalence of heterozygotes in the
      general population was 0.08 percent (95 percent confidence interval, 0.03 to 0.16
      percent) for both the Arg3500Gln and the Arg3531Cys mutations, and 0.00 percent
      (95 percent confidence interval, 0.00 to 0.18 percent) for the Arg3500Trp
      mutation. Among carriers of the Arg3500Gln mutation, cholesterol levels were
      significantly higher than among noncarriers in the general population - by 100 mg
      per deciliter (2.6 mmol per liter) among carriers in the general population, 154
      mg per deciliter (4.0 mmol per liter) among patients with ischemic heart disease,
      and 172 mg per deciliter (4.5 mmol per liter) among patients with familial
      hypercholesterolemia. Heterozygous carriers of the Arg3500Gln mutation were
      significantly more common among patients with ischemic heart disease (odds ratio,
      7.0; 95 percent confidence interval, 2.2 to 22; P=0.003) and patients with
      familial hypercholesterolemia (odds ratio, 78; 95 percent confidence interval, 16
      to 388; P=0.001) than in the general population. Heterzygous carriers of the
      Arg3531Cys mutation in the general population did not have higher-than-normal
      plasma cholesterol levels or an increased risk of ischemic heart disease (odds
      ratio; 1.4; 95 percent confidence interval, 0.2 to 11; P=0.54). CONCLUSIONS: The
      Arg3500Gln mutation in the apolipoprotein B gene, which is responsible for
      familial defective apolipoprotein B-100 and is present in approximately 1 in 1000
      persons in Denmark, causes severe hypercholesterolemia and increases the risk of
      ischemic heart disease.

PMID- 9603796
TI  - Transient angiolymphoid hyperplasia and Kaposi's sarcoma after primary infection
      with human herpesvirus 8 in a patient with human immunodeficiency virus
      infection.

PMID- 9603797
TI  - Images in clinical medicine. Achilles'-tendon xanthoma in familial
      hypercholesterolemia.

PMID- 9603798
TI  - Eosinophilia.

PMID- 9603799
TI  - Neuropathies associated with paraproteinemia.

PMID- 9603801
TI  - Asbestos--still a carcinogen.

PMID- 9603802
TI  - Preventing blindness in premature infants.

PMID- 9603803
TI  - Must good HMOs go bad? Second of two parts. The search for checks and balances.

PMID- 9603804
TI  - Mercury methylation by interspecies hydrogen and acetate transfer between
      sulfidogens and methanogens.
AB  - Cocultures of Desulfovibrio desulfuricans and Methanococcus maripaludis grew on
      sulfate-free lactate medium while vigorously methylating Hg2+. Individually,
      neither bacterium could grow or methylate mercury in this medium. Similar
      synergistic growth of sulfidogens and methanogens may create favorable conditions
      for Hg2+ methylation in low-sulfate anoxic freshwater sediments.

PMID- 9603805
TI  - The contribution of caseins to the amino acid supply for Lactococcus lactis
      depends on the type of cell envelope proteinase.
AB  - The ability of caseins to fulfill the amino acid requirements of Lactococcus
      lactis for growth was studied as a function of the type of cell envelope
      proteinase (PI versus PIII type). Two genetically engineered strains of L. lactis
      that differed only in the type of proteinase were grown in chemically defined
      media containing alphas1-, beta-, and kappa-caseins (alone or in combination) as
      the sources of amino acids. Casein utilization resulted in limitation of the
      growth rate, and the extent of this limitation depended on the type of casein and
      proteinase. Adding different mixtures of essential amino acids to the growth
      medium made it possible to identify the nature of the limitation. This procedure
      also made it possible to identify the amino acid deficiency which was growth rate
      limiting for L. lactis in milk (S. Helinck, J. Richard, and V. Juillard, Appl.
      Environ. Microbiol. 63:2124-2130, 1997) as a function of the type of proteinase.
      Our results were compared with results from previous in vitro experiments in
      which casein degradation by purified proteinases was examined. The results were
      in agreement only in the case of the PI-type proteinase. Therefore, our results
      bring into question the validity of the in vitro approach to identification of
      casein-derived peptides released by a PIII-type proteinase.

PMID- 9603806
TI  - Isolation and characterization of pediocin AcH chimeric protein mutants with
      altered bactericidal activity.
AB  - A collection of pediocin AcH amino acid substitution mutants was generated by PCR
      random mutagenesis of DNA encoding the bacteriocin. Mutants were isolated by
      cloning mutagenized DNA into an Escherichia coli malE plasmid that directs the
      secretion of maltose binding protein-pediocin AcH chimeric proteins and by
      screening transformant colonies for bactericidal activity against Lactobacillus
      plantarum NCDO955 (K. W. Miller, R. Schamber, Y. Chen, and B. Ray, 1998. Appl.
      Environ. Microbiol. 64:14-20, 1998). In all, 17 substitution mutants were
      isolated at 14 of the 44 amino acids of pediocin AcH. Seven mutants (N5K, C9R,
      C14S, C14Y, G37E, G37R, and C44W) were completely inactive against the pediocin
      AcH-sensitive strains L. plantarum NCDO955, Listeria innocua Lin11, Enterococcus
      faecalis M1, Pediococcus acidilactici LB42, and Leuconostoc mesenteroides Ly. A
      C24S substitution mutant constructed by other means also was inactive against
      these bacteria. Nine other mutants (K1N, W18R, I26T, M31T, A34D, N41K, H42L,
      K43N, and K43E) retained from <1% to approximately 60% of wild-type activity when
      assayed against L. innocua Lin11. One mutant, K11E, displayed approximately 2. 8
      fold-higher activity against this indicator. About one half of the mutations
      mapped to amino acids that are conserved in the pediocin-like family of
      bacteriocins. All four cysteines were found to be required for activity, although
      only C9 and C14 are conserved among pediocin-like bacteriocins. Several basic
      amino acids as well as nonpolar amino acids located within the hydrophobic C
      terminal region also were found to be important. The mutations are discussed in
      the context of structural models that have been proposed for the bacteriocin.

PMID- 9603807
TI  - Two nearly identical aromatic compound hydrolase genes in a strong
      polychlorinated biphenyl degrader, Rhodococcus sp. strain RHA1.
AB  - The two 2-hydroxy-6-oxohepta-2,4-dienoate (HOHD) hydrolase genes, etbD1 and
      etbD2, were cloned from a strong polychlorinated biphenyl (PCB) degrader,
      Rhodococcus sp. strain RHA1, and their nucleotide sequences were determined. The
      etbD2 gene was located in the vicinity of bphA gene homologs and encoded an
      enzyme whose amino-terminal sequence was very similar to the amino-terminal
      sequence of the HOHD hydrolase which was purified from RHA1. Using the etbD2 gene
      fragment as a probe, we cloned the etbD1 gene encoding the purified HOHD
      hydrolase by colony hybridization. Both genes encode a product having 274 amino
      acid residues and containing the nucleophile motif conserved in alpha/beta
      hydrolase fold enzymes. The deduced amino acid sequences were quite similar to
      the amino acid sequences of the products of the single-ring aromatic hydrolase
      genes, such as dmpD, cumD, todF, and xylF, and not very similar to the amino acid
      sequences of the products of bphD genes from PCB degraders, including RHA1. The
      two HOHD hydrolase genes and the RHA1 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoate
      (HPDA) hydrolase gene, bphD, were expressed in Escherichia coli, and their
      relative enzymatic activities were examined. The product of bphD was very
      specific to HPDA, and the products of etbD1 and etbD2 were specific to HOHD. All
      of the gene products exhibited poor activities against the meta-cleavage product
      of catechol. These results agreed with the results obtained for BphD and EtbD1
      hydrolases purified from RHA1. The three hydrolase genes exhibited similar
      induction patterns both in an RNA slot blot hybridization analysis and in a
      reporter gene assay when a promoter probe vector was used. They were induced by
      biphenyl, ethylbenzene, benzene, toluene, and ortho-xylene. Strain RCD1, an RHA1
      mutant strain lacking both the bphD gene and the etbD2 gene, grew well on
      ethylbenzene. This result suggested that the etbD1 gene product is involved in
      the meta-cleavage metabolic pathway of ethylbenzene.

PMID- 9603808
TI  - The gal genes for the Leloir pathway of Lactobacillus casei 64H.
AB  - The gal genes from the chromosome of Lactobacillus casei 64H were cloned by
      complementation of the galK2 mutation of Escherichia coli HB101. The pUC19
      derivative pKBL1 in one complementation-positive clone contained a 5.8-kb DNA
      HindIII fragment. Detailed studies with other E. coli K-12 strains indicated that
      plasmid pKBL1 contains the genes coding for a galactokinase (GalK), a galactose 1
      phosphate-uridyltransferase (GalT), and a UDP-galactose 4-epimerase (GalE). In
      vitro assays demonstrated that the three enzymatic activities are expressed from
      pKBL1. Sequence analysis revealed that pKBL1 contained two additional genes, one
      coding for a repressor protein of the LacI-GalR-family and the other coding for
      an aldose 1-epimerase (mutarotase). The gene order of the L. casei gal operon is
      galKETRM. Because parts of the gene for the mutarotase as well as the promoter
      region upstream of galK were not cloned on pKBL1, the regions flanking the
      HindIII fragment of pKBL1 were amplified by inverse PCR. Northern blot analysis
      showed that the gal genes constitute an operon that is transcribed from two
      promoters. The galKp promoter is inducible by galactose in the medium, while
      galEp constitutes a semiconstitutive promoter located in galK.

PMID- 9603809
TI  - Comparison of gas chromatography and mineralization experiments for measuring
      loss of selected polychlorinated biphenyl congeners in cultures of white rot
      fungi.
AB  - Two methods were used to compare the biodegradation of six polychlorinated
      biphenyl (PCB) congeners by 12 white rot fungi. Four fungi were found to be more
      active than Phanerochaete chrysosporium ATCC 24725. Biodegradation of the
      following congeners was monitored by gas chromatography: 2,3-dichlorobiphenyl,
      4,4'-dichlorobiphenyl, 2,4',5-trichlorobiphenyl (2,4',5-TCB), 2,2',4,4'
      tetrachlorobiphenyl, 2,2',5,5'-tetrachlorobiphenyl, and 2,2',4,4',5,5'
      hexachlorobiphenyl. The congener tested for mineralization was 2,4',5-[U-14C]TCB.
      Culture supernatants were also assayed for lignin peroxidase and manganese
      peroxidase activities. Of the fungi tested, two strains of Bjerkandera adusta
      (UAMH 8258 and UAMH 7308), one strain of Pleurotus ostreatus (UAMH 7964), and
      Trametes versicolor UAMH 8272 gave the highest biodegradation and mineralization.
      P. chrysosporium ATCC 24725, a strain frequently used in studies of PCB
      degradation, gave the lowest mineralization and biodegradation activities of the
      12 fungi reported here. Low but detectable levels of lignin peroxidase and
      manganese peroxidase activity were present in culture supernatants, but no
      correlation was observed among any combination of PCB congener biodegradation,
      mineralization, and lignin peroxidase or manganese peroxidase activity. With the
      exception of P. chrysosporium, congener loss ranged from 40 to 96%; however,
      these values varied due to nonspecific congener binding to fungal biomass and
      glassware. Mineralization was much lower, </=11%, because it measures a complete
      oxidation of at least part of the congener molecule but the results were more
      consistent and therefore more reliable in assessment of PCB biodegradation.

PMID- 9603810
TI  - Reduction of the 2,2'-Azinobis(3-ethylbenzthiazoline-6-sulfonate) cation radical
      by physiological organic acids in the absence and presence of manganese 
AB  - Laccase is a copper-containing phenoloxidase, involved in lignin degradation by
      white rot fungi. The laccase substrate range can be extended to include
      nonphenolic lignin subunits in the presence of a noncatalytic cooxidant such as
      2, 2'-azinobis(3-ethylbenzthiazoline-6-sulfonate) (ABTS), with ABTS being
      oxidized to the stable cation radical, ABTS.+, which accumulates. In this report,
      we demonstrate that the ABTS.+ can be efficiently reduced back to ABTS by
      physiologically occurring organic acids such as oxalate, glyoxylate, and
      malonate. The reduction of the radical by oxalate results in the formation of
      H2O2, indicating the formation of O2.- as an intermediate. O2.- itself was shown
      to act as an ABTS.+ reductant. ABTS.+ reduction and H2O2 formation are strongly
      stimulated by the presence of Mn2+, with accumulation of Mn3+ being observed.
      Additionally, 4-methyl-O-isoeugenol, an unsaturated lignin monomer model, is
      capable of directly reducing ABTS.+. These data suggest several mechanisms for
      the reduction of ABTS.+ which would permit the effective use of ABTS as a laccase
      cooxidant at catalytic concentrations.

PMID- 9603812
TI  - Spreadsheet method for evaluation of biochemical reaction rate coefficients and
      their uncertainties by weighted nonlinear least-squares analysis of the
      integrated monod equation 
AB  - A convenient method for evaluation of biochemical reaction rate coefficients and
      their uncertainties is described. The motivation for developing this method was
      the complexity of existing statistical methods for analysis of biochemical rate
      equations, as well as the shortcomings of linear approaches, such as Lineweaver
      Burk plots. The nonlinear least-squares method provides accurate estimates of the
      rate coefficients and their uncertainties from experimental data. Linearized
      methods that involve inversion of data are unreliable since several important
      assumptions of linear regression are violated. Furthermore, when linearized
      methods are used, there is no basis for calculation of the uncertainties in the
      rate coefficients. Uncertainty estimates are crucial to studies involving
      comparisons of rates for different organisms or environmental conditions. The
      spreadsheet method uses weighted least-squares analysis to determine the best-fit
      values of the rate coefficients for the integrated Monod equation. Although the
      integrated Monod equation is an implicit expression of substrate concentration,
      weighted least-squares analysis can be employed to calculate approximate
      differences in substrate concentration between model predictions and data. An
      iterative search routine in a spreadsheet program is utilized to search for the
      best-fit values of the coefficients by minimizing the sum of squared weighted
      errors. The uncertainties in the best-fit values of the rate coefficients are
      calculated by an approximate method that can also be implemented in a
      spreadsheet. The uncertainty method can be used to calculate single-parameter
      (coefficient) confidence intervals, degrees of correlation between parameters,
      and joint confidence regions for two or more parameters. Example sets of
      calculations are presented for acetate utilization by a methanogenic mixed
      culture and trichloroethylene cometabolism by a methane-oxidizing mixed culture.
      An additional advantage of application of this method to the integrated Monod
      equation compared with application of linearized methods is the economy of
      obtaining rate coefficients from a single batch experiment or a few batch
      experiments rather than having to obtain large numbers of initial rate
      measurements. However, when initial rate measurements are used, this method can
      still be used with greater reliability than linearized approaches.

PMID- 9603811
TI  - Towards a biocatalyst for (S)-styrene oxide production: characterization of the
      styrene degradation pathway of Pseudomonas sp. strain VLB120.
AB  - In order to design a biocatalyst for the production of optically pure styrene
      oxide, an important building block in organic synthesis, the metabolic pathway
      and molecular biology of styrene degradation in Pseudomonas sp. strain VLB120 was
      investigated. A 5.7-kb XhoI fragment, which contained on the same strand of DNA
      six genes involved in styrene degradation, was isolated from a gene library of
      this organism in Escherichia coli by screening for indigo formation. T7 RNA
      polymerase expression experiments indicated that this fragment coded for at least
      five complete polypeptides, StyRABCD, corresponding to five of the six genes. The
      first two genes encoded the potential carboxy-terminal part of a sensor, named
      StySc, and the complete response regulator StyR. Fusion of the putative styAp
      promoter to a lacZ reporter indicated that StySc and StyR together regulate
      expression of the structural genes at the transcriptional level. Expression of
      styScR also alleviated a block that prevented translation of styA mRNA when a
      heterologous promoter was used. The structural genes styA and styB produced a
      styrene monooxygenase that converted styrene to styrene oxide, which was then
      converted to phenylacetaldehyde by StyC. Sequence homology analysis of StyD
      indicated a probable function as a phenylacetaldehyde dehydrogenase. To assess
      the usefulness of the enzymes for the production of enantiomerically pure styrene
      oxide, we investigated the enantiospecificities of the reactions involved.
      Kinetic resolution of racemic styrene oxide by styrene oxide isomerase was
      studied with E. coli recombinants carrying styC, which converted styrene oxide at
      a very high rate but with only a slight preference for the S enantiomer. However,
      recombinants producing styrene monooxygenase catalyzed the formation of (S)
      styrene oxide from inexpensive styrene with an excellent enantiomeric excess of
      more than 99% at rates up to 180 U g (dry weight) of cells-1.

PMID- 9603813
TI  - Occurrence of a sequence in marine cyanophages similar to that of T4 g20 and its
      application to PCR-based detection and quantification techniques.
AB  - Viruses are ubiquitous components of marine ecosystems and are known to infect
      unicellular phycoerythrin-containing cyanobacteria belonging to the genus
      Synechococcus. A conserved region from the cyanophage genome was identified in
      three genetically distinct cyanomyoviruses, and a sequence analysis revealed that
      this region exhibited significant similarity to a gene encoding a capsid assembly
      protein (gp20) from the enteric coliphage T4. The results of a comparison of gene
      20 sequences from three cyanomyoviruses and T4 allowed us to design two
      degenerate PCR primers, CPS1 and CPS2, which specifically amplified a 165-bp
      region from the majority of cyanomyoviruses tested. A competitive PCR (cPCR)
      analysis revealed that cyanomyovirus strains could be accurately enumerated, and
      it was demonstrated that quantification was log-linear over ca. 3 orders of
      magnitude. Different calibration curves were obtained for each of the three
      cyanomyovirus strains tested; consequently, cPCR performed with primers CPS1 and
      CPS2 could lead to substantial inaccuracies in estimates of phage abundance in
      natural assemblages. Further sequence analysis of cyanomyovirus gene 20 homologs
      would be necessary in order to design primers which do not exhibit phage-to-phage
      variability in priming efficiency. It was demonstrated that PCR products of the
      correct size could be amplified from seawater samples following 100x
      concentration and even directly without any prior concentration. Hence, the use
      of degenerate primers in PCR analyses of cyanophage populations should provide
      valuable data on the diversity of cyanophages in natural assemblages. Further
      optimization of procedures may ultimately lead to a sensitive assay which can be
      used to analyze natural cyanophage populations both quantitatively (by cPCR) and
      qualitatively following phylogenetic analysis of amplified products.

PMID- 9603814
TI  - Development of a genetic transformation system for an alga-lysing bacterium.
AB  - Four marine bacteria, Alteromonas sp. strains A27, A28, A29, and A30, that lyse
      the diatom Skeletonema costatum NIES-324 were isolated from coastal seawater
      samples. They were also able to lyse the diatoms Thalassiosira sp. and Eucampia
      zodiacs and the raphidophycean flagellate Chattonella antiqua. Cryptic indigenous
      plasmids, designated pAS28 and pAS29, were detected in Alteromonas sp. strains
      A28 and A29, respectively. These plasmids appeared to be similar based on size
      and restriction site analysis. A shuttle vector that replicates in Escherichia
      coli and Alteromonas sp. strain A28 was constructed by fusing pAS28 and E. coli
      vector pCRIIc. The 16-kbp chimeric plasmid, designated pASS1, had the ability to
      transform strain A28 at a frequency of 10(6) transformants per microg of DNA.
      Deletion analysis of pASS1 showed that the 4.7-kb EcoRI-HindIII region of pAS28
      was essential for plasmid maintenance in strain A28. This EcoRI-HindIII fragment
      contained an open reading frame which appeared to encode a 708-amino-acid
      protein.

PMID- 9603815
TI  - Effects of above-optimum growth temperature and cell morphology on
      thermotolerance of Listeria monocytogenes cells suspended in bovine milk.
AB  - The thermotolerances of two different cell forms of Listeria monocytogenes
      (serotype 4b) grown at 37 and 42.8 degrees C in commercially pasteurized and
      laboratory-tyndallized whole milk (WM) were investigated. Test strains, after
      growth at 37 or 42.8 degreesC, were suspended in WM at concentrations of
      approximately 1.5 x 10(8) to 3.0 x 10(8) cells/ml and were then heated at 56, 60,
      and 63 degrees C for various exposure times. Survival was determined by
      enumeration on tryptone-soya-yeast extract agar and Listeria selective agar, and
      D values (decimal reduction times) and Z values (numbers of degrees Celsius
      required to cause a 10-fold change in the D value) were calculated. Higher
      average recovery and higher D values (i.e., seen as a 2.5- to 3-fold increase in
      thermotolerance) were obtained when cells were grown at 42.8 degrees C prior to
      heat treatment. A relationship was observed between thermotolerance and cell
      morphology of L. monocytogenes. Atypical Listeria cell types (consisting
      predominantly of long cell chains measuring up to 60 micron in length) associated
      with rough (R) culture variants were shown to be 1.2-fold more thermotolerant
      than the typical dispersed cell form associated with normal smooth (S) cultures
      (P </= 0.001). The thermal death-time (TDT) curves of R-cell forms contained a
      tail section in addition to the shoulder section characteristic of TDT curves of
      normal single to paired cells (i.e., S form). The factors shown to influence the
      thermoresistance of suspended Listeria cells (P </= 0.001) were as follows:
      growth and heating temperatures, type of plating medium, recovery method, and
      cell morphology. Regression analysis of nonlinear data can underestimate survival
      of L. monocytogenes; the end point recovery method was shown to be a better
      method for determining thermotolerance because it takes both shoulders and tails
      into consideration. Despite their enhanced heat resistance, atypical R-cell forms
      of L. monocytogenes were unable to survive the low-temperature, long-time
      pasteurization process when freely suspended and heated in WM.

PMID- 9603816
TI  - Construction of an efficient biologically contained pseudomonas putida strain and
      its survival in outdoor assays 
AB  - Active biological containment systems consist of two components, a killing
      element designed to induce cell death and a control element which modulates the
      expression of the killing function. We constructed a mini-Tn5 transposon bearing
      a fusion of the Plac promoter to the gef killing gene and a fusion of the Pm
      promoter to the lacI gene plus the positive regulator of the Pm promoter, the
      xylS gene. This mini-Tn5 transposon was transferred to the chromosome of
      Pseudomonas putida CMC4, and in culture this strain survived in the presence of 3
      methylbenzoate (an XylS effector) and committed suicide in the absence of this
      aromatic compound. The rate of killing escape was on the order of 10(-8) per cell
      and per generation. This contained strain and an uncontained control strain were
      used in outdoor tests performed in the spring-summer and autumn-winter periods to
      determine their survival in planted and unplanted soils with and without 3
      methylbenzoate. In unplanted soils the numbers of both the contained strain and
      the uncontained strain per gram of soil tended to decrease, but the numbers of
      the contained strain decreased faster in soils without 3-methylbenzoate. The
      decrease in the number of CFU per gram of soil was faster in the spring-summer
      period than in the autumn-winter period. In planted soils survival in the
      rhizosphere and survival in bulk soil were studied. In the rhizosphere the
      uncontained control strain tended to become established at levels on the order of
      10(5) to 10(6) CFU/g of soil regardless of the presence of 3-methylbenzoate. In
      the bulk soil the numbers of bacterial cells were 2 to 3 orders of magnitude
      lower. In planted soils the contained strain tended to disappear, but this
      tendency was more pronounced in the absence of 3-methylbenzoate and occurred
      faster in the summer assay than in the winter assay. We found no evidence of
      dispersal of the test strains outside the experimental plots.

PMID- 9603817
TI  - Isolation, characterization, molecular gene cloning, and sequencing of a novel
      phytase from Bacillus subtilis.
AB  - The Bacillus subtilis strain VTT E-68013 was chosen for purification and
      characterization of its excreted phytase. Purified enzyme had maximal phytase
      activity at pH 7 and 55 degrees C. Isolated enzyme required calcium for its
      activity and/or stability and was readily inhibited by EDTA. The enzyme proved to
      be highly specific since, of the substrates tested, only phytate, ADP, and ATP
      were hydrolyzed (100, 75, and 50% of the relative activity, respectively). The
      phytase gene (phyC) was cloned from the B. subtilis VTT E-68013 genomic library.
      The deduced amino acid sequence (383 residues) showed no homology to the
      sequences of other phytases nor to those of any known phosphatases. PhyC did not
      have the conserved RHGXRXP sequence found in the active site of known phytases,
      and therefore PhyC appears not to be a member of the phytase subfamily of
      histidine acid phosphatases but a novel enzyme having phytase activity. Due to
      its pH profile and optimum, it could be an interesting candidate for feed
      applications.

PMID- 9603819
TI  - Female fertility and mating type distribution in a south african population of
      fusarium subglutinans f. sp. pini 
AB  - Fusarium subglutinans f. sp. pini is the causal agent of pitch canker disease of
      pines. The initial occurrence of F. subglutinans f. sp. pini in South Africa was
      limited to a single nursery, and isolates from this population are capable of
      reproducing sexually. We determined the effective population number, Ne, of this
      population by using mating type and male/hermaphrodite polymorphisms as
      indicators. The effective population number for mating type, Ne(mt), is 99% of
      the count (total population), and that for male/hermaphrodite status, Ne(f), is
      42 to 46% of the count (total population). The number of strains that can
      function as the female parent limits the effective population number of this
      population. If this population is stable, then, depending upon assumptions about
      mutation and selection, sexual reproduction need occur only once per 26 to 153
      asexual generations to maintain this level of sexual fertility.

PMID- 9603818
TI  - Genes for 2,4,5-trichlorophenoxyacetic acid metabolism in Burkholderia cepacia
      AC1100: characterization of the tftC and tftD genes and locations of the tft
      operons on multiple replicons.
AB  - Burkholderia cepacia AC1100 uses the chlorinated aromatic compound 2, 4,5
      trichlorophenoxyacetic acid (2,4,5-T) as a sole source of carbon and energy. The
      enzyme which converts the first intermediate in the pathway, 2,4,5
      trichlorophenol, to 5-chlorohydroquinone has been purified and consists of two
      subunits of 58 and 22 kDa, encoded by the tftC and tftD genes (48). A degenerate
      primer was designed from the N terminus of the 58-kDa polypeptide and used to
      isolate a clone containing the tftC and tftD genes from a genomic library of
      AC1100. The derived amino acid sequences of tftC and tftD show significant
      homology to the two-component monooxygenases HadA of Burkholderia pickettii,
      HpaBC of Escherichia coli, and HpaAH of Klebsiella pneumonia. Expression of the
      tftC and tftD genes appeared to be induced when they were grown in the presence
      of 2,4,5-T, as shown by RNA slot blot and primer extension analyses. Three sets
      of cloned tft genes were used as probes to explore the genomic organization of
      the pathway. Pulsed-field gel electrophoresis analyses of whole chromosomes of B.
      cepacia AC1100 demonstrated that the genome is comprised of five replicons of
      4.0, 2.7, 0.53, 0.34, and 0.15 Mbp, designated I to V, respectively. The tft
      genes are located on the smaller replicons: the tftAB cluster is on replicon IV,
      tftEFGH is on replicon III, and copies of the tftC and the tftCD operons are
      found on both replicons III and IV. When cells were grown in the absence of 2,4,5
      T, the genes were lost at high frequency by chromosomal deletions and
      rearrangements to produce 2,4,5-T-negative mutants. In one mutant, the tftA and
      tftB genes translocated from one replicon to another, with the concomitant loss
      of tftEFGH and one copy of tftCD.

PMID- 9603820
TI  - Genotypic characterization of Bradyrhizobium strains nodulating endemic woody
      legumes of the Canary Islands by PCR-restriction fragment length polymorphism
      analysis of genes encoding 16S rRNA (16S rDNA) and 16S-23S rDNA intergenic
      spacers, repetitive extragenic palindromic PCR genomic fingerprinting, and
      partial 16S rDNA sequencing.
AB  - We present a phylogenetic analysis of nine strains of symbiotic nitrogen-fixing
      bacteria isolated from nodules of tagasaste (Chamaecytisus proliferus) and other
      endemic woody legumes of the Canary Islands, Spain. These and several reference
      strains were characterized genotypically at different levels of taxonomic
      resolution by computer-assisted analysis of 16S ribosomal DNA (rDNA) PCR
      restriction fragment length polymorphisms (PCR-RFLPs), 16S-23S rDNA intergenic
      spacer (IGS) RFLPs, and repetitive extragenic palindromic PCR (rep-PCR) genomic
      fingerprints with BOX, ERIC, and REP primers. Cluster analysis of 16S rDNA
      restriction patterns with four tetrameric endonucleases grouped the Canarian
      isolates with the two reference strains, Bradyrhizobium japonicum USDA 110spc4
      and Bradyrhizobium sp. strain (Centrosema) CIAT 3101, resolving three genotypes
      within these bradyrhizobia. In the analysis of IGS RFLPs with three enzymes, six
      groups were found, whereas rep-PCR fingerprinting revealed an even greater
      genotypic diversity, with only two of the Canarian strains having similar
      fingerprints. Furthermore, we show that IGS RFLPs and even very dissimilar rep
      PCR fingerprints can be clustered into phylogenetically sound groupings by
      combining them with 16S rDNA RFLPs in computer-assisted cluster analysis of
      electrophoretic patterns. The DNA sequence analysis of a highly variable 264-bp
      segment of the 16S rRNA genes of these strains was found to be consistent with
      the fingerprint-based classification. Three different DNA sequences were
      obtained, one of which was not previously described, and all belonged to the B.
      japonicum/Rhodopseudomonas rDNA cluster. Nodulation assays revealed that none of
      the Canarian isolates nodulated Glycine max or Leucaena leucocephala, but all
      nodulated Acacia pendula, C. proliferus, Macroptilium atropurpureum, and Vigna
      unguiculata.

PMID- 9603821
TI  - Bsn-t alleles from french field strains of agaricus bisporus 
AB  - In the Agaricus bisporus desert population in California, the dominant Bsn-t
      allele determines the production of tetrasporic basidia and homokaryotic spores
      (n) that characterize a heterothallic life cycle. Strains belonging to a French
      population have the Bsn-b/b genotype that results in bisporic basidia that
      produce heterokaryotic spores (n + n) which characterize a pseudohomothallic life
      cycle. More recombination occurs in the tetrasporic population than in the
      bisporic population. In France, tetrasporic strains are rare. For two such
      isolates, Bs 261 and Bs 423, we determined the life cycle, the heritability of
      the tetrasporic trait, the amount of variation in the recombination rate, and the
      haploid fruiting ability. We found that (i) Bs 261 was heterothallic, (ii) Bs 423
      was homokaryotic and homothallic, (iii) Bs 261 was Bsn-t/b, (iv) recombination on
      a segment of chromosome I depended on the genotype at BSN, (v) some of the
      homokaryotic offspring of Bs 261 and all of the progeny of Bs 423 were able to
      fruit, (vi) Bs 261 and Bs 423 were closely related, and (vii) Bs 423 was
      partially intersterile with other strains of the species.

PMID- 9603823
TI  - Fate of residual lignin during delignification of kraft pulp by trametes
      versicolor 
AB  - The fungus Trametes versicolor can delignify and brighten kraft pulps. To better
      understand the mechanism of this biological bleaching and the by-products formed,
      I traced the transformation of pulp lignin during treatment with the fungus.
      Hardwood and softwood kraft pulps containing 14C-labelled residual lignin were
      prepared by laboratory pulping of lignin-labelled aspen and spruce wood and then
      incubated with T. versicolor. After initially polymerizing the lignin, the fungus
      depolymerized it to alkali-extractable forms and then to soluble forms. Most of
      the labelled carbon accumulated in the water-soluble pool. The extractable and
      soluble products were oligomeric; single-ring aromatic products were not
      detected. The mineralization of the lignin carbon to CO2 varied between
      experiments, up to 22% in the most vigorous cultures. The activities of the known
      enzymes laccase and manganese peroxidase did not account for all of the lignin
      degradation that took place in the T. versicolor cultures. This fungus may
      produce additional enzymes that could be useful in enzyme bleaching systems.

PMID- 9603822
TI  - Influence of reduced water activity on lactose metabolism by lactococcus lactis
      subsp. cremoris At different pH values 
AB  - The influence of reduced water activity (aw) on lactose metabolism by Lactococcus
      lactis subsp. cremoris 2254 and 2272 was studied at different pH values. In
      control incubations (aw, 0.99) with nongrowing cells in pH-controlled phosphate
      buffer, the levels of carbon recovered as L-(+)-lactate were 92% at pH 6.1 and
      5.3 and 78% at pH 4.5. However, the levels of recovery decreased to approximately
      50% at all pH values tested when the aw was 0.88 (with glycerol as the
      humectant). When growing cells in broth controlled at pH 6.3 were used, a
      reduction in the aw from 0.99 to 0.96 resulted in a decrease in the level of
      lactose carbon recovered as L-(+)-lactate from 100 to 71%. Low levels of L-(+)
      lactate carbon recovery (<50%) were also observed with cells resuspended in pH
      uncontrolled reconstituted skim milk at aw values of 0.99 and 0. 87 and in young
      cheese curds. The missing lactose carbon could not be accounted for by acetate,
      ethanol, formate, acetaldehyde, or pyruvate. Attempts were made to determine
      where the missing lactose carbon was diverted to under the stress conditions
      used. Some of the missing lactose carbon was recovered as galactose (0.1 to 2.5
      mM) in culture supernatants. Decreasing either the aw or the pH resulted in
      increased galactose accumulation by nongrowing cells; adjusting both
      environmental factors together potentiated the effect. The sensitivities of the
      two lactococcal strains tested were different; strain 2272 was more prone to
      accumulate galactose under stress conditions. A methyl pentose(s) and additional
      galactose were found in acid-hydrolyzed supernatants from cultures containing
      both growing and nongrowing cells, indicating that a saccharide(s) rich in these
      components was formed by lactococci under low-aw and low-pH stress conditions.

PMID- 9603824
TI  - Low-frequency horizontal transfer of an element containing the chlorocatechol
      degradation genes from Pseudomonas sp. strain B13 to Pseudomonas putida F1 and to
      indigenous bacteria in laboratory-scale activated-sludge microcosms.
AB  - The possibilities for low-frequency horizontal transfer of the self-transmissible
      chlorocatechol degradative genes (clc) from Pseudomonas sp. strain B13 were
      investigated in activated-sludge microcosms. When the clc genes were transferred
      into an appropriate recipient bacterium such as Pseudomonas putida F1, a new
      metabolic pathway for chlorobenzene degradation was formed by complementation
      which could be selected for by the addition of mono- or 1, 4-dichlorobenzene
      (CB). Under optimized conditions with direct donor-recipient filter matings, very
      low transfer frequencies were observed (approximately 3.5 x 10(-8) per donor per
      24 h). In contrast, in matings on agar plate surfaces, transconjugants started to
      appear after 8 to 10 days, and their numbers then increased during prolonged
      continuous incubation with CB. In activated-sludge microcosms, CB-degrading (CB+)
      transconjugants of strain F1 which had acquired the clc genes were detected but
      only when strain B13 cell densities of more than 10(5) CFU/ml could be maintained
      by the addition of its specific growth substrate, 3-chlorobenzoate (3CBA). The
      CB+ transconjugants reached final cell densities of between 10(2) and 10(3)
      CFU/ml. When strain B13 was inoculated separately (without the designated
      recipient strain F1) into an activated-sludge microcosm, CB+ transconjugants
      could not be detected. However, in this case a new 3CBA-degrading strain appeared
      which had acquired the clc genes from strain B13. The effects of selective
      substrates on the survival and growth of and gene transfer between bacteria
      degrading aromatic pollutants in a wastewater ecosystem are discussed.

PMID- 9603825
TI  - Effects of pyruvate decarboxylase overproduction on flux distribution at the
      pyruvate branch point in Saccharomyces cerevisiae.
AB  - A multicopy plasmid carrying the PDC1 gene (encoding pyruvate decarboxylase; Pdc)
      was introduced in Saccharomyces cerevisiae CEN. PK113-5D. The physiology of the
      resulting prototrophic strain was compared with that of the isogenic prototrophic
      strain CEN.PK113-7D and an empty-vector reference strain. In glucose-grown shake
      flask cultures, the introduction of the PDC1 plasmid caused a threefold increase
      in the Pdc level. In aerobic glucose-limited chemostat cultures growing at a
      dilution rate of 0.10 h-1, Pdc levels in the overproducing strain were 14-fold
      higher than those in the reference strains. Levels of glycolytic enzymes
      decreased by ca. 15%, probably due to dilution by the overproduced Pdc protein.
      In chemostat cultures, the extent of Pdc overproduction decreased with increasing
      dilution rate. The high degree of overproduction of Pdc at low dilution rates did
      not affect the biomass yield. The dilution rate at which aerobic fermentation set
      in decreased from 0.30 h-1 in the reference strains to 0.23 h-1 in the Pdc
      overproducing strain. In the latter strain, the specific respiration rate reached
      a maximum above the dilution rate at which aerobic fermentation first occurred.
      This result indicates that a limited respiratory capacity was not responsible for
      the onset of aerobic fermentation in the Pdc-overproducing strain. Rather, the
      results indicate that Pdc overproduction affected flux distribution at the
      pyruvate branch point by influencing competition for pyruvate between Pdc and the
      mitochondrial pyruvate dehydrogenase complex. In respiratory cultures (dilution
      rate, <0.23 h-1), Pdc overproduction did not affect the maximum glycolytic
      capacity, as determined in anaerobic glucose-pulse experiments.

PMID- 9603826
TI  - Cometabolism of 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene by Pseudomonas
      acidovorans M3GY grown on biphenyl.
AB  - 1,1-Dichloro-2,2-bis(4-chlorophenyl)ethylene (DDE), a toxic breakdown product of
      1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT), has traditionally been
      viewed as a dead-end metabolite: there are no published reports detailing
      enzymatic ring fission of DDE by bacteria in either soil or pure culture. In this
      study, we investigated the ability of Pseudomonas acidovorans M3GY to transform
      DDE and its unchlorinated analog, 1,1-diphenylethylene (DPE). While strain M3GY
      could grow on DPE, cells grown on DPE as a sole carbon source could not degrade
      DDE. Cells grown on biphenyl, however, did degrade DDE. Mass balance analysis of
      [14C]DDE showed transformation of more than 40% of the recoverable radioactivity.
      Nine chlorinated metabolites produced from DDE were identified by gas
      chromatography-mass spectrometry-Fourier-transform infrared spectrometry (GC-MS
      FTIR) from cultures grown on biphenyl. Recovery of these metabolites demonstrates
      that biphenyl-grown cells degrade DDE through a meta-fission pathway. This study
      provides a possible model for biodegradation of DDE in soil by biphenyl-utilizing
      bacteria.

PMID- 9603827
TI  - Role of Streptococcus thermophilus MR-1C capsular exopolysaccharide in cheese
      moisture retention.
AB  - Recent work by our group has shown that an exopolysaccharide (EPS)-producing
      starter pair, Streptococcus thermophilus MR-1C and Lactobacillus delbrueckii
      subsp. bulgaricus MR-1R, can significantly increase moisture retention in low-fat
      mozzarella (D. B. Perry, D. J. McMahon, and C. J. Oberg, J. Dairy Sci. 80:799
      805, 1997). The objectives of this study were to determine whether MR-1C, MR-1R,
      or both of these strains are required for enhanced moisture retention and to
      establish the role of EPS in this phenomenon. Analysis of low-fat mozzarella made
      with different combinations of MR-1C, MR-1R, and the non-EPS-producing starter
      culture strains S. thermophilus TA061 and Lactobacillus helveticus LH100 showed
      that S. thermophilus MR-1C was responsible for the increased cheese moisture
      level. To investigate the role of the S. thermophilus MR-1C EPS in cheese
      moisture retention, the epsE gene in this bacterium was inactivated by gene
      replacement. Low-fat mozzarella made with L. helveticus LH100 plus the non-EPS
      producing mutant S. thermophilus DM10 had a significantly lower moisture content
      than did cheese made with strains LH100 and MR-1C, which confirmed that the MR-1C
      capsular EPS was responsible for the water-binding properties of this bacterium
      in cheese. Chemical analysis of the S. thermophilus MR-1C EPS indicated that the
      polymer has a novel basic repeating unit composed of D-galactose, L-rhamnose, and
      L-fucose in a ratio of 5:2:1.

PMID- 9603828
TI  - Enzymological characteristics of the hyperthermostable NAD-dependent glutamate
      dehydrogenase from the archaeon Pyrobaculum islandicum and effects of denaturants
      and organic solvents.
AB  - NAD-dependent glutamate dehydrogenase (L-glutamate:NAD oxidoreductase,
      deaminating; EC 1.4.1.2) was purified to homogeneity from a crude extract of the
      continental hyperthermophilic archaeon Pyrobaculum islandicum by two successive
      Red Sepharose CL-4B affinity chromatographies. The enzyme is the most
      thermostable NAD-dependent dehydrogenase found to date; the activity was not lost
      after incubation at 100 degrees C for 2 h. The enzyme activity increased linearly
      with temperature, and the maximum was observed at ca. 90 degrees C. The enzyme
      has a molecular mass of about 220 kDa and consists of six subunits with identical
      molecular masses of 36 kDa. The enzyme required NAD as a coenzyme for L-glutamate
      deamination and was different from the NADP-dependent glutamate dehydrogenase
      from other hyperthermophiles. The Km values for NAD, L-glutamate, NADH, 2
      oxoglutarate, and ammonia were 0.025, 0.17, 0.0050, 0.066, and 9.7 mM,
      respectively. The enzyme activity was significantly increased by the addition of
      denaturants such as guanidine hydrochloride and some water-miscible organic
      solvents such as acetonitrile and tetrahydrofuran. When fluorescence of the
      enzyme was measured in the presence of guanidine hydrochloride, a significant
      emission spectrum change and a shift in the maximum were observed but not in the
      presence of urea. These results indicate that this hyperthermophilic enzyme may
      have great potential in applications to biosensor and bioreactor processes.

PMID- 9603830
TI  - Variants of smooth Salmonella enterica serovar Enteritidis that grow to higher
      cell density than the wild type are more virulent.
AB  - Salmonella enterica serovar Enteritidis that grows to a higher cell density (SE
      HCD) than wild type while retaining O-chain lipopolysaccharide was isolated by
      transforming wild type serovar Enteritidis with the cell density sensor plasmid
      pSB402 and selecting for bioluminescence. A luminescent strain, SE-HCD, that
      emitted light in proportion with cell density and opacity through stationary
      phase was isolated. After a peak cell density of 1.5 x 10(11) CFU/ml was
      observed, luminescence decreased, although opacity continued to increase.
      Scanning electron microscopy revealed that changes in luminescence and opacity
      past peak cell density were associated with lysis of a swarming hyperflagellated
      coccobacillary cell type and emergence of a 10-to-30-fold-elongated rod cell type
      that lacked cell surface structures. Vigorous aeration was required to induce
      this dramatic cellular differentiation. The virulence of two isogenic variants
      with different patterns of light emission at an opacity of 0.2 after the culture
      was diluted 10-fold (1/10 OD) was assessed in animal models. Whereas SE-HCD1
      killed 70% of 6-day-old chicks challenged subcutaneously, the same dose of SE
      HCD2 did not kill any chicks. Conversely, subcutaneous challenge of hens with SE
      HCD2 contaminated eggs five and seven times more often, respectively, than did SE
      HCD1 or wild type serovar Enteritidis. Intravenous challenge with SE-HCD2
      contaminated 22% of eggs versus 0. 5% with wild type, depressed egg production
      for 4 weeks, and caused clinical signs of Gallinarum Disease (Fowl Typhoid) in
      hens. SE-HCD2 produced no contaminated eggs following oral infection, whereas
      wild type contaminated 1.3% of eggs. Thus, SE-HCD2 is better at contaminating
      eggs than wild type, but only by parenteral challenge. These results suggest that
      it may be possible to separate luminescent serovar Enteritidis into groups that
      infect different age groups and organs and contaminate eggs.

PMID- 9603831
TI  - Structure of a microbial community in soil after prolonged addition of low levels
      of simulated acid rain 
AB  - Humus samples were collected 12 growing seasons after the start of a simulated
      acid rain experiment situated in the subarctic environment. The acid rain was
      simulated with H2SO4, a combination of H2SO4 and HNO3, and HNO3 at two levels of
      moderate acidic loads close to the natural anthropogenic pollution levels of
      southern Scandinavia. The higher levels of acid applications resulted in
      acidification, as defined by humus chemistry. The concentrations of base cations
      decreased, while the concentrations of exchangeable H+, Al, and Fe increased.
      Humus pH decreased from 3.83 to 3.65. Basal respiration decreased with decreasing
      humus pH, and total microbial biomass, measured by substrate-induced respiration
      and total amount of phospholipid fatty acids (PLFA), decreased slightly. An
      altered PLFA pattern indicated a change in the microbial community structure at
      the higher levels of acid applications. In general, branched fatty acids, typical
      of gram-positive bacteria, increased in the acid plots. PLFA analysis performed
      on the bacterial community growing on agar plates also showed that the relative
      amount of PLFA specific for gram-positive bacteria increased due to the
      acidification. The changed bacterial community was adapted to the more acidic
      environment in the acid-treated plots, even though bacterial growth rates,
      estimated by thymidine and leucine incorporation, decreased with pH. Fungal
      activity (measured as acetate incorporation into ergosterol) was not affected.
      This result indicates that bacteria were more affected than fungi by the
      acidification. The capacity of the bacterial community to utilize 95 different
      carbon sources was variable and only showed weak correlations to pH. Differences
      in the toxicities of H2SO4 and HNO3 for the microbial community were not found.

PMID- 9603829
TI  - Effects of midgut-protein-preparative and ligand binding procedures on the toxin
      binding characteristics of BT-R1, a common high-affinity receptor in Manduca
      sexta for Cry1A Bacillus thuringiensis toxins.
AB  - The identity of the physiologically important Cry1A receptor protein(s) in the
      lepidopteran Manduca sexta has been a matter of dispute due to the multiple
      proteins which bind the Cry1Ac toxin. Cry1Aa, Cry1Ab, and Cry1Ac exhibit
      essentially identical toxicities toward M. sexta larvae and show a high degree of
      sequence and presumed structural identities. These similarities make it likely
      that there is a common mechanism of toxicity in these lepidopteran-specific
      toxins in terms of both mode of action and the receptor proteins through which
      these toxins exert their lepidopteran-specific toxicity. Investigators in our
      laboratory previously demonstrated that the cloned 210-kDa glycoprotein BT-R1
      binds all three Cry1A toxins (T. P. Keeton and L. A. Bulla, Jr., Appl. Environ.
      Microbiol. 63:3419-3425, 1997). This protein remains a common binding protein
      even after being subjected to various midgut membrane preparation and processing
      protocols. The method used to isolate proteins from the M. sexta larval midgut in
      no significant way affects the results of ligand binding and vacuum blotting
      experiments, and we have been unable to detect specific, high-affinity binding of
      any Cry1A toxin to Cry1Ac binding proteins other than BT-R1. Alterations in blot
      substrate and blocking, hybridization, and washing buffers support these
      conclusions. Collectively, these results indicate that in M. sexta the cadherin
      like BT-R1 protein is a common high-affinity receptor protein for the Cry1A
      family of toxins.

PMID- 9603832
TI  - Reduction of soluble iron and reductive dissolution of ferric iron-containing
      minerals by moderately thermophilic iron-oxidizing bacteria 
AB  - Five moderately thermophilic iron-oxidizing bacteria, including representative
      strains of the three classified species (Sulfobacillus thermosulfidooxidans,
      Sulfobacillus acidophilus, and Acidimicrobium ferrooxidans), were shown to be
      capable of reducing ferric iron to ferrous iron when they were grown under oxygen
      limitation conditions. Iron reduction was most readily observed when the isolates
      were grown as mixotrophs or heterotrophs with glycerol as an electron donor; in
      addition, some strains were able to couple the oxidation of tetrathionate to the
      reduction of ferric iron. Cycling of iron between the ferrous and ferric states
      was observed during batch culture growth in unshaken flasks incubated under
      aerobic conditions, although the patterns of oxidoreduction of iron varied in
      different species of iron-oxidizing moderate thermophiles and in strains of a
      single species (S. acidophilus). All three bacterial species were able to grow
      anaerobically with ferric iron as a sole electron acceptor; the growth yields
      correlated with the amount of ferric iron reduced when the isolates were grown in
      the absence of oxygen. One of the moderate thermophiles (identified as a strain
      of S. acidophilus) was able to bring about the reductive dissolution of three
      ferric iron-containing minerals (ferric hydroxide, jarosite, and goethite) when
      it was grown under restricted aeration conditions with glycerol as a carbon and
      energy source. The significance of iron reduction by moderately thermophilic iron
      oxidizers in both environmental and applied contexts is discussed.

PMID- 9603834
TI  - Development of a probiotic cheddar cheese containing human-derived Lactobacillus
      paracasei strains.
AB  - Cheddar cheese was manufactured with either Lactobacillus salivarius NFBC 310,
      NFBC 321, or NFBC 348 or L. paracasei NFBC 338 or NFBC 364 as the dairy starter
      adjunct. These five strains had previously been isolated from the human small
      intestine and have been characterized extensively with respect to their probiotic
      potential. Enumeration of these strains in mature Cheddar cheese, however, was
      complicated by the presence of high numbers (>10(7) CFU/g of cheese) of
      nonstarter lactic acid bacteria, principally composed of lactobacilli which
      proliferate as the cheese ripens. Attempts to differentiate the adjunct
      lactobacilli from the nonstarter lactobacilli based on bile tolerance and growth
      temperature were unsuccessful. In contrast, the randomly amplified polymorphic
      DNA method allowed the generation of discrete DNA fingerprints for each strain
      which were clearly distinguishable from those generated from the natural flora of
      the cheeses. Using this approach, it was found that both L. paracasei strains
      grew and sustained high viability in cheese during ripening, while each of the L.
      salivarius species declined over the ripening period. These data demonstrate that
      Cheddar cheese can be an effective vehicle for delivery of some probiotic
      organisms to the consumer.

PMID- 9603833
TI  - Structure of the beta-galactosidase gene from Thermus sp. strain T2: expression
      in Escherichia coli and purification in a single step of an active fusion
      protein.
AB  - The nucleotide sequence of both the bgaA gene, coding for a thermostable beta
      galactosidase of Thermus sp. strain T2, and its flanking regions was determined.
      The deduced amino acid sequence of the enzyme predicts a polypeptide of 645 amino
      acids (Mr, 73,595). Comparative analysis of the open reading frames located in
      the flanking regions of the bgaA gene revealed that they might encode proteins
      involved in the transport and hydrolysis of sugars. The observed homology between
      the deduced amino acid sequences of BgaA and the beta-galactosidase of Bacillus
      stearothermophilus allows us to classify the new enzyme within family 42 of
      glycosyl hydrolases. BgaA was overexpressed in its active form in Escherichia
      coli, but more interestingly, an active chimeric beta-galactosidase was
      constructed by fusing the BgaA protein to the choline-binding domain of the major
      pneumococcal autolysin. This chimera illustrates a novel approach for producing
      an active and thermostable hybrid enzyme that can be purified in a single step by
      affinity chromatography on DEAE-cellulose, retaining the catalytic properties of
      the native enzyme. The chimeric enzyme showed a specific activity of 191,000 U/mg
      at 70 degrees C and a Km value of 1.6 mM with o-nitrophenyl-beta-D
      galactopyranoside as a substrate, and it retained 50% of its initial activity
      after 1 h of incubation at 70 degrees C.

PMID- 9603835
TI  - Characterization of metabolites in the biotransformation of 2,4,6-trinitrotoluene
      with anaerobic sludge: role of triaminotoluene.
AB  - The present study describes the biotransformation of 2,4,6-trinitrotoluene (TNT)
      (220 microM) by using anaerobic sludge (10%, vol/vol) supplemented with molasses
      (3.3 g/liter). Despite the disappearance of TNT in less than 15 h, roughly 0.1%
      of TNT was attributed to mineralization (14CO2). A combination of solid-phase
      microextraction-gas chromatography-mass spectrometry and liquid chromatography
      mass spectrometry identified two distinctive cycles in the degradation of TNT.
      One cycle was responsible for the stepwise reduction of TNT to eventually produce
      triaminotoluene (TAT) in relatively high yield (160 microM). The other cycle
      involved TAT and was responsible for the production of azo derivatives, e.g.,
      2,2',4,4'-tetraamino-6,6'-azotoluene (2,2',4, 4'-TA-6,6'-azoT) and 2,2',6,6'
      tetraamino-4,4'-azotoluene (2,2',6, 6'-TA-4,4'-azoT) at pH 7.2. These azo
      compounds were also detected when TAT was treated with the anaerobic sludge but
      not with an autoclaved sludge, suggesting the biotic nature of their formation.
      When the anaerobic conditions in the TAT-containing culture medium were removed
      by aeration and/or acidification (pH 3), the corresponding phenolic compounds,
      e.g., hydroxy-diaminotoluenes and dihydroxy-aminotoluenes, were observed at room
      temperature. Trihydroxytoluene was detected only after heating TAT in water at
      100 degrees C. When 13CH3-labeled TNT was used as the N source in the above
      microcosms, we were unable to detect 13C-labeled p-cresol or [13CH3]toluene,
      indicating the absence of denitration or deamination in the biodegradation
      process. The formation and disappearance of TAT were not accompanied by
      mineralization, suggesting that TAT acted as a dead-end metabolite.

PMID- 9603836
TI  - Rapid and reliable identification of food-borne yeasts by Fourier-transform
      infrared spectroscopy.
AB  - Computer-based Fourier-transform infrared spectroscopy (FT-IR) was used to
      identify food-borne, predominantly fermentative yeasts. Dried yeast suspensions
      provided the films suitable for FT-IR measurement. Informative windows in the
      spectrum were selected and combined to achieve optimal results. A reference
      spectrum library was assembled, based on 332 defined yeast strains from
      international yeast collections and our own isolates. All strains were identified
      with conventional methods using physiological and morphological characteristics.
      In order to assess identification quality, another 722 unknown yeast isolates not
      included in the reference spectrum library were identified both by classical
      methods and by comparison of their FT-IR spectra with those of the reference
      spectrum library. Ninety-seven and one-half percent of these isolates were
      identified correctly by FT-IR. Easy handling, rapid identification within 24 h
      when starting from a single colony, and a high differentiation capacity thus
      render FT-IR technology clearly superior to other routine methods for the
      identification of yeasts.

PMID- 9603837
TI  - Isolation and characterization of a dibenzofuran-degrading yeast: identification
      of oxidation and ring cleavage products.
AB  - We characterized the ability of a yeast to cleave the aromatic structure of the
      dioxin-like compound dibenzofuran. The yeast strain was isolated from a dioxin
      contaminated soil sample and identified as Trichosporon mucoides. During
      incubation of glucose-pregrown cells with dibenzofuran, six major metabolites
      were detected by high-performance liquid chromatography. The formation of four
      different monohydroxylated dibenzofurans was proven by comparison of analytical
      data (gas chromatography-mass spectrometry) with that for authentic standards.
      Further oxidation produced 2, 3-dihydroxydibenzofuran and its ring cleavage
      product 2-(1-carboxy methylidene)-2,3-dihydrobenzo[b]furanylidene glycolic acid,
      which were characterized by mass spectrometry and 1H nuclear magnetic resonance
      spectroscopy. These two metabolites are derived from 2-hydroxydibenzofuran and 3
      hydroxydibenzofuran, as shown by incubation experiments using these
      monohydroxylated dibenzofurans as substrates.

PMID- 9603838
TI  - Hemoglobin biosynthesis in Vitreoscilla stercoraria DW: cloning, expression, and
      characterization of a new homolog of a bacterial globin gene.
AB  - In the strictly aerobic, gram-negative bacterium Vitreoscilla strain C1, oxygen
      limited growth conditions create a more than 50-fold increase in the expression
      of a homodimeric heme protein which was recognized as the first bacterial
      hemoglobin (Hb). The recently determined crystal structure of Vitreoscilla Hb has
      indicated that the heme pocket of microbial globins differs from that of
      eukaryotic Hbs. In an attempt to understand the diverse functions of Hb-like
      proteins in prokaryotes, we have cloned and characterized the gene (vgb) encoding
      an Hb-like protein from another strain of Vitreoscilla, V. stercoraria DW.
      Several silent changes were observed within the coding region of the V.
      stercoraria vgb gene. Apart from that, V. stercoraria Hb exhibited interesting
      differences between the A and E helices. Compared to its Hb counterpart from
      Vitreoscilla strain C1, the purified preparation of V. stercoraria Hb displays a
      slower autooxidation rate. The differences between Vitreoscilla Hb and V.
      stercoraria Hb were mapped onto the three-dimensional structure of Vitreoscilla
      Hb, which indicated that the four changes, namely, Ile7Val, Ile9Thr, Ile10Ser,
      and Leu62Val, present within the V. stercoraria Hb fall in the region where the A
      and E helices contact each other. Therefore, alteration in the relative
      orientation of the A and E helices and the corresponding conformational change in
      the heme binding pocket of V. stercoraria Hb can be correlated to its slower
      autooxidation rate. In sharp contrast to the oxygen-regulated biosynthesis of Hb
      in Vitreoscilla strain C1, production of Hb in V. stercoraria has been found to
      be low and independent of oxygen control, which is supported by the absence of a
      fumarate and nitrate reductase regulator box within the V. stercoraria vgb
      promoter region. Thus, the regulation mechanisms of the Hb-encoding gene appear
      to be quite different in the two closely related species of Vitreoscilla. The
      relatively slower autooxidation rate of V. stercoraria Hb, lack of oxygen
      sensitivity, and constitutive production of Hb suggest that it may have some
      other function(s) in the cellular physiology of V. stercoraria DW, together with
      facilitated oxygen transport, predicted for earlier reported Vitreoscilla Hb.

PMID- 9603840
TI  - Growth of geobacter sulfurreducens with acetate in syntrophic cooperation with
      hydrogen-oxidizing anaerobic partners 
AB  - Pure cultures of Geobacter sulfurreducens and other Fe(III)-reducing bacteria
      accumulated hydrogen to partial pressures of 5 to 70 Pa with acetate, butyrate,
      benzoate, ethanol, lactate, or glucose as the electron donor if electron release
      to an acceptor was limiting. G. sulfurreducens coupled acetate oxidation with
      electron transfer to an anaerobic partner bacterium in the absence of ferric iron
      or other electron acceptors. Cocultures of G. sulfurreducens and Wolinella
      succinogenes with nitrate as the electron acceptor degraded acetate efficiently
      and grew with doubling times of 6 to 8 h. The hydrogen partial pressures in these
      acetate-degrading cocultures were considerably lower, in the range of 0.02 to
      0.04 Pa. From these values and the concentrations of the other reactants, it was
      calculated that in this cooperation the free energy change available to G.
      sulfurreducens should be about -53 kJ per mol of acetate oxidized, assuming
      complete conversion of acetate to CO2 and H2. However, growth yields (18.5 g of
      dry mass per mol of acetate for the coculture, about 14 g for G. sulfurreducens)
      indicated considerably higher energy gains. These yield data, measurement of
      hydrogen production rates, and calculation of the diffusive hydrogen flux
      indicated that electron transfer in these cocultures may not proceed exclusively
      via interspecies hydrogen transfer but may also proceed through an alternative
      carrier system with higher redox potential, e.g., a c-type cytochrome that was
      found to be excreted by G. sulfurreducens into the culture fluid. Syntrophic
      acetate degradation was also possible with G. sulfurreducens and Desulfovibrio
      desulfuricans CSN but only with nitrate as electron acceptor. These cultures
      produced cell yields of 4.5 g of dry mass per mol of acetate, to which both
      partners contributed at about equal rates. These results demonstrate that some
      Fe(III)-reducing bacteria can oxidize organic compounds under Fe(III) limitation
      with the production of hydrogen, and they provide the first example of rapid
      acetate oxidation via interspecies electron transfer at moderate temperature.

PMID- 9603839
TI  - Transcriptional activation of the Aspergillus nidulans gpdA promoter by osmotic
      signals.
AB  - A differentially expressed gpdA cDNA clone was isolated from NaCl-adapted
      Aspergillus nidulans (FGSC359) and identified as glyceraldehyde-3-phosphate
      dehydrogenase (gpdA) on the basis of its nucleotide sequence. The level of gpdA
      RNA substantially increased in cultures gradually adapted to NaCl but was greatly
      reduced in cultures exposed briefly to a high concentration of NaCl. A pyrG
      auxotroph of A. nidulans (A773) was cotransformed with a gpdA-uidA construct and
      a plasmid containing the Neurospora crassa pyr4 gene as a selectable marker. One
      pyrG+ beta-glucuronidase-positive (GUS+) transformant was selected, and stable
      integration of the gpdA-uidA construct into the genome was confirmed by Southern
      blot analysis. Gradual adaptation to increasing concentrations of NaCl resulted
      in an increase in GUS activity to 2.7-fold. GUS activity was reduced after a 2-h
      exposure of an unadapted culture to 2 M NaCl but gradually increased to a maximum
      of twofold after 24 h. GUS activity also increased by 8.4-fold in Na2SO4-adapted
      cultures, 4.9-fold in polyethylene glycol-adapted cultures, and 7.5-fold in KCl
      adapted cultures. These results are consistent with the hypothesis that the A.
      nidulans gpdA promoter is transcriptionally activated by osmotic signals.

PMID- 9603841
TI  - Effect of temperature oscillation on insect cell growth and baculovirus
      replication 
AB  - Temperature oscillation can enhance cell viability of sf9 insect cells and
      baculovirus production of occlusion bodies (OB) and extracellular virus (ECV)
      compared with constant temperature in stationary culture and suspension culture.
      The optimal oscillation range was 24 to 28 degreesC. At this temperature
      oscillation, the viability of uninfected and infected sf9 cells can be maintained
      much longer than at 28 degreesC. Although the rate of virus infection was a
      little low at 24 to 28 degreesC, the final cell infectivity was similar to that
      at a constant temperature of 28 degreesC. The production of OB was increased from
      13.4 to 17.4/cell in stationary culture and from 13.9/cell to 18.1/cell in
      suspension culture. The titer of ECV was increased from 87 to 114 PFU/cell in
      stationary culture and from 79 to 114 PFU/cell in suspension culture.

PMID- 9603842
TI  - New unstable variants of green fluorescent protein for studies of transient gene
      expression in bacteria.
AB  - Use of the green fluorescent protein (Gfp) from the jellyfish Aequorea victoria
      is a powerful method for nondestructive in situ monitoring, since expression of
      green fluorescence does not require any substrate addition. To expand the use of
      Gfp as a reporter protein, new variants have been constructed by the addition of
      short peptide sequences to the C-terminal end of intact Gfp. This rendered the
      Gfp susceptible to the action of indigenous housekeeping proteases, resulting in
      protein variants with half-lives ranging from 40 min to a few hours when
      synthesized in Escherichia coli and Pseudomonas putida. The new Gfp variants
      should be useful for in situ studies of temporal gene expression.

PMID- 9603843
TI  - Establishment of new genetic traits in a microbial biofilm community.
AB  - Conjugational transfer of the TOL plasmid (pWWO) was analyzed in a flow chamber
      biofilm community engaged in benzyl alcohol degradation. The community consisted
      of three species, Pseudomonas putida RI, Acinetobacter sp. strain C6, and an
      unidentified isolate, D8. Only P. putida RI could act as a recipient for the TOL
      plasmid. Cells carrying a chromosomally integrated lacIq gene and a lacp-gfp
      tagged version of the TOL plasmid were introduced as donor strains in the biofilm
      community after its formation. The occurrence of plasmid-carrying cells was
      analyzed by viable-count-based enumeration of donors and transconjugants. Upon
      transfer of the plasmids to the recipient cells, expression of green fluorescence
      was activated as a result of zygotic induction of the gfp gene. This allowed a
      direct in situ identification of cells receiving the gfp-tagged version of the
      TOL plasmid. Our data suggest that the frequency of horizontal plasmid transfer
      was low, and growth (vertical transfer) of the recipient strain was the major
      cause of plasmid establishment in the biofilm community. Employment of scanning
      confocal laser microscopy on fixed biofilms, combined with simultaneous
      identification of P. putida cells and transconjugants by 16S rRNA hybridization
      and expression of green fluorescence, showed that transconjugants were always
      associated with noninfected P. putida RI recipient microcolonies. Pure colonies
      of transconjugants were never observed, indicating that proliferation of
      transconjugant cells preferentially took place on preexisting P. putida RI
      microcolonies in the biofilm.

PMID- 9603844
TI  - Mycobacterium avium bacilli grow saprozoically in coculture with Acanthamoeba
      polyphaga and survive within cyst walls.
AB  - Protozoans are gaining recognition as environmental hosts for a variety of
      waterborne pathogens. We compared the growth of Mycobacterium avium, a human
      pathogen associated with domestic water supplies, in coculture with the free
      living amoeba Acanthamoeba polyphaga with the growth of M. avium when it was
      separated from amoebae by a 0.1-micron-pore-size polycarbonate membrane (in a
      parachamber). Although viable mycobacteria were observed within amoebal vacuoles,
      there was no significant difference between bacterial growth in coculture and
      bacterial growth in the parachamber. This suggests that M. avium is able to grow
      saprozoically on products secreted by the amoebae. In contrast, Legionella
      pneumophila, a well-studied intracellular parasite of amoebae, multiplied only in
      coculture. A comparison of amoebae infected with L. pneumophila and amoebae
      infected with M. avium by electron microscopy demonstrated that there were
      striking differences in the locations of the bacteria within amoebal cysts. While
      L. pneumophila resided within the cysts, M. avium was found within the outer
      walls of the double-walled cysts of A. polyphaga. These locations may provide a
      reservoir for the bacteria when environmental conditions become unfavorable.

PMID- 9603845
TI  - Randomly amplified polymorphic DNA PCR analysis of bovine Cryptosporidium parvum
      strains isolated from the watershed of the Red River of the North.
AB  - Cryptosporidium parvum is a protozoan parasite that causes the disease
      cryptosporidiosis in a variety of mammals, including neonatal calves and humans.
      Millions of oocysts are shed during acute cryptosporidiosis, and zoonotic
      transmission is inferred, though not proven, to be a general phenomenon. Very
      little is known about the degree of strain variation exhibited by bovine and
      human isolates, though such knowledge would enable the amount of bovine-to-human
      transmission to be more precisely analyzed. This research was initiated to
      determine whether variations exist among bovine strains isolated from a localized
      geographic area, the watershed of the Red River of the North. Sixteen strains
      were isolated and compared to each other and to two human and two calf strains
      from Australia by randomly amplified polymorphic DNA PCR. A statistical analysis
      of the data indicated that the isolates belonged to four different groups of
      strains.

PMID- 9603846
TI  - Estimation of nitrifying bacterial activities by measuring oxygen uptake in the
      presence of the metabolic inhibitors allylthiourea and azide 
AB  - The effects of two metabolic inhibitors on an enriched nitrifying biomass during
      incubation for short periods of time were investigated by determining
      respirometric measurements. Allylthiourea (86 &mgr;M) and azide (24 &mgr;M) were
      shown to be strong, selective inhibitors of ammonia and nitrite oxidation,
      respectively. Consequently, a differential respirometry method for estimating
      nitrifying and heterotrophic bacterial activities within a mixed biomass is
      proposed.

PMID- 9603847
TI  - Antagonistic activity of Lactobacillus plantarum C11: two new two-peptide
      bacteriocins, plantaricins EF and JK, and the induction factor plantaricin A.
AB  - Six bacteriocinlike peptides (plantaricin A [PlnA], PlnE, PlnF, PlnJ, PlnK, and
      PlnN) produced by Lactobacillus plantarum C11 were detected by amino acid
      sequencing and mass spectrometry. Since purification to homogeneity was
      problematic, all six peptides were obtained by solid-phase peptide synthesis and
      were tested for bacteriocin activity. It was found that L. plantarum C11 produces
      two two-peptide bacteriocins (PlnEF and PlnJK); a strain-specific antagonistic
      activity was detected at nanomolar concentrations when PlnE and PlnF were
      combined and when PlnJ and PlnK were combined. Complementary peptides were at
      least 10(3) times more active when they were combined than when they were present
      individually, and optimal activity was obtained when the complementary peptides
      were present in approximately equal amounts. The interaction between
      complementary peptides was specific, since neither PlnE nor PlnF could complement
      PlnJ or PlnK, and none of these peptides could complement the peptides
      constituting the two-peptide bacteriocin lactococcin G. Interestingly, PlnA,
      which acts as an extracellular signal (pheromone) that triggers bacteriocin
      production, also possessed a strain-specific antagonistic activity. No
      bacteriocin activity could be detected for PlnN.

PMID- 9603848
TI  - Effects of manganese peroxidase on residual lignin of softwood kraft pulp 
AB  - Manganese peroxidase treatment lowered the kappa number of kraft pulp and
      increased the alkali extractability of the residual lignin but did not directly
      solubilize it. This indicates that MnP partially oxidizes the lignin in the pulp
      but does not degrade it to soluble fragments.

PMID- 9603850
TI  - Detection of Toxoplasma gondii oocysts in drinking water.
AB  - The world's largest outbreak of waterborne toxoplasmosis occurred in a
      municipality in the western Canadian province of British Columbia. When drinking
      water emerged as a possible source of infection during the outbreak
      investigation, a laboratory method was needed to attempt detection of the
      parasite, Toxoplasma gondii. The method developed was based on the current U.S.
      Environmental Protection Agency method for detection of Cryptosporidium oocysts.
      Collection of large-volume drinking water samples and cartridge filter processing
      were unchanged, although identification of Toxoplasma oocysts in the filter
      retentate was carried out by using a previously described rodent model.
      Validation of the method developed was tested by using oocysts from a well
      characterized Toxoplasma strain.

PMID- 9603849
TI  - Culture conditions control expression of the genes for aflatoxin and
      sterigmatocystin biosynthesis in Aspergillus parasiticus and A. nidulans.
AB  - High temperature and nitrate supported gene expression for sterigmatocystin
      biosynthesis in Aspergillus nidulans; ammonium did not. Homologous genes for
      aflatoxin biosynthesis in A. parasiticus showed the opposite transcript
      expression pattern, suggesting that the two mycotoxins are regulated differently.
      The aflR gene is postulated to require additional genetic elements to effect its
      own activation by the different culture conditions. A patulin polyketide synthase
      (PKS) gene was found to be regulated differently than the aflatoxin PKS. Thus,
      the biosyntheses of structurally similar compounds in these two fungi appear to
      be regulated very differently.

PMID- 9603851
TI  - Method detection limits of PCR and immunofluorescence assay for Cryptosporidium
      parvum in soil.
AB  - We determined and compared the method detection limits (MDLalpha) of a PCR and an
      immunofluorescence assay (IFA) for detection of Cryptosporidium parvum oocysts in
      soils. Based on the MDLalpha and the quantitative nature and stability of the
      IFA, PCR analysis is not a useful screening step for soil studies of oocyst
      transport.

PMID- 9603852
TI  - Detection of Cyclospora cayetanensis in wastewater.
AB  - Cyclospora cayetanensis causes diarrheal disease worldwide without a confirmed
      mode of transmission. Wastewater was examined for the presence of this organism.
      Oocysts were detected microscopically, and their identity was confirmed by
      molecular techniques. These findings verify that current techniques can isolate
      Cyclospora oocysts and suggest that fecally contaminated water may act as a
      vehicle of transmission.

PMID- 9603853
TI  - Evaluation of lacticin 3147 and a teat seal containing this bacteriocin for
      inhibition of mastitis pathogens.
AB  - Lacticin 3147 is a broad-spectrum bacteriocin produced by Lactococcus lactis
      subsp. lactis DPC3147 which is bactericidal against a range of mastitis-causing
      streptococci and staphylococci. In this study, both lacticin 3147 and the
      lantibiotic nisin were separately incorporated into an intramammary teat seal
      product. The seal containing lacticin 3147 exhibited excellent antimicrobial
      activity and might form the basis of an improved treatment for the prevention of
      mastitis in dry cows.

PMID- 9603854
TI  - Phosphoenolpyruvate phosphomutase activity in an L-phosphonoalanine-mineralizing
      strain of burkholderia cepacia 
AB  - A strain of Burkholderia cepacia isolated by enrichment culture utilized L-2
      amino-3-phosphonopropionic acid (phosphonoalanine) at concentrations up to 20 mM
      as a carbon, nitrogen, and phosphorus source in a phosphate-insensitive manner.
      Cells contained phosphoenolpyruvate phosphomutase activity, presumed to be
      responsible for cleavage of the C---P bond of phosphonopyruvate, the
      transamination product of L-phosphonoalanine; this was inducible in the presence
      of phosphonoalanine.

PMID- 9603855
TI  - Computation of the electrical double layer properties of semipermeable membranes
      in multicomponent electrolytes 
AB  - A methodology is presented for calculating of the surface potential, Donnan
      potential, and ion concentration profiles for semipermeable microbial membranes
      that is valid for an arbitrary electrolyte composition. This model for surface
      potential, Donnan potential, and charge density was applied to recently reported
      experimental data for gram-positive bacteria, including Bacillus brevis,
      Rhodococcus opacus, Rhodococcus erythropolis, and Corynebacterium species. These
      calculations show that previously unconsidered trace amounts of divalent and
      trivalent cations at very low concentrations (10(-6) M) can have significant
      effects on the calculated surface and Donnan potentials, at ionic strengths of I
      </= 0.01 M, and that these effects need to be considered in accurate modeling of
      microbial surface. In addition, the calculated ion concentration profiles show
      that owing to the relatively high surface charges that can develop in microbial
      membranes, electrostatic effects can act to significantly concentrate divalent
      (factors of 5 x 10(3)) and trivalent (factors of 2 x 10(4)) cations within the
      bacterial cell wall. Comparison of the calculated concentration factors with
      those derived from experiments shows that a significant fraction of the uptake of
      metal by bacteria can be explained by the proposed electrostatic model.

PMID- 9603856
TI  - Kinetics of acetate oxidation by two sulfate reducers isolated from anaerobic
      granular sludge 
AB  - Kinetic parameters of acetate oxidation were determined for the sulfate reducers
      Desulforhabdus amnigenus and Desulfobacca acetoxidans. Based on these parameters,
      both sulfate reducers seem to be able to outcompete Methanosaeta spp. for acetate
      in acetate-fed anaerobic bioreactors. Mixed-substrate studies showed that D.
      amnigenus degraded acetate and hydrogen simultaneously but preferred lactate,
      propionate, and ethanol over acetate.

PMID- 9603857
TI  - Impact on arbuscular mycorrhiza formation of pseudomonas strains used as
      inoculants for biocontrol of soil-borne fungal plant pathogens 
AB  - The arbuscular mycorrhizal symbiosis, a key component of agroecosystems, was
      assayed as a rhizosphere biosensor for evaluation of the impact of certain
      antifungal Pseudomonas inoculants used to control soil-borne plant pathogens. The
      following three Pseudomonas strains were tested: wild-type strain F113, which
      produces the antifungal compound 2,4-diacetylphloroglucinol (DAPG); strain
      F113G22, a DAPG-negative mutant of F113; and strain F113(pCU203), a DAPG
      overproducer. Wild-type strain F113 and mutant strain F113G22 stimulated both
      mycelial development from Glomus mosseae spores germinating in soil and tomato
      root colonization. Strain F113(pCU203) did not adversely affect G. mosseae
      performance. Mycelial development, but not spore germination, is sensitive to 10
      &mgr;M DAPG, a concentration that might be present in the rhizosphere. The
      results of scanning electron and confocal microscopy demonstrated that strain
      F113 and its derivatives adhered to G. mosseae spores independent of the ability
      to produce DAPG.

PMID- 9603858
TI  - Seasonal abundance of lysogenic bacteria in a subtropical estuary 
AB  - Seasonal changes in the abundance of inducible lysogenic bacteria in a eutrophic
      estuarine environment were investigated over a 13-month period. Biweekly water
      samples were collected from Tampa Bay, Fla., and examined for prophage induction
      by mitomycin C treatment. At the conclusion of the study, we determined that
      52.2% of the samples displayed prophage induction, as indicated by significant
      increases in viral direct counts compared with uninduced controls. Samples that
      displayed prophage induction occurred during the warmer months (February through
      October), when surface water temperatures were above 19 degreesC, and no
      induction was observed in November, December, or January. This study presents
      clear evidence that there is seasonal variation in the number of inducible
      lysogenic bacteria in an estuarine environment.

PMID- 9603859
TI  - Myoglobin as an inhibitor of exopeptidases from lactobacillus sake 
AB  - The effects of myoglobin on exopeptidases of Lactobacillus sake were determined.
      Inhibition of the aminopeptidases increased as the myoglobin concentration
      increased; aminopeptidase 3 was the most affected (90% inhibition).
      Aminopeptidases 1, 2, and 4 showed similar inhibition levels (around 60%).
      Myoglobin did not affect tripeptidase activity. Thus, myoglobin could limit amino
      acid generation in meat systems.

PMID- 9603860
TI  - Isolation of a bacterial strain with the ability to utilize the sulfonated azo
      compound 4-carboxy-4'-sulfoazobenzene as the sole source of carbon and energy.
AB  - A bacterial strain (strain S5) which grows aerobically with the sulfonated azo
      compound 4-carboxy-4'-sulfoazobenzene as the sole source of carbon and energy was
      isolated. This strain was obtained by continuous adaptation of "Hydrogenophaga
      palleronii" S1, which has the ability to grow aerobically with 4
      aminobenzenesulfonate. Strain S5 probably cleaves 4-carboxy-4'-sulfoazobenzene
      reductively under aerobic conditions to 4-aminobenzoate and 4-aminobenzene
      sulfonate, which are mineralized by previously established degradation pathways.

PMID- 9603861
TI  - Bioencapsulation of two different vibrio species in nauplii of the brine shrimp
      (Artemia franciscana) 
AB  - Two groups of nauplii from the brine shrimp (Artemia franciscana) were enriched
      with different bacteria, and the dynamics of bacterial uptake by the nauplii were
      observed. This study showed that the efficiency of Artemia nauplii in
      bioencapsulating bacteria strongly depends on the type of bacteria used, time of
      exposure, and status (live or dead) of the bacteria.

PMID- 9603862
TI  - The atzABC genes encoding atrazine catabolism are located on a self-transmissible
      plasmid in Pseudomonas sp. strain ADP.
AB  - Pseudomonas sp. strain ADP initiates atrazine catabolism via three enzymatic
      steps, encoded by atzA, -B, and -C, which yield cyanuric acid, a nitrogen source
      for many bacteria. In-well lysis, Southern hybridization, and plasmid transfer
      studies indicated that the atzA, -B, and -C genes are localized on a 96-kb self
      transmissible plasmid, pADP-1, in Pseudomonas sp. strain ADP. High-performance
      liquid chromatography analyses showed that cyanuric acid degradation was not
      encoded by pADP-1. pADP-1 was transferred to Escherichia coli strains at a
      frequency of 4.7 x 10(-2). This suggests a potential molecular mechanism for the
      dispersion of the atzABC genes to other soil bacteria.

PMID- 9603863
TI  - Desulfurization of dibenzothiophene and diesel oils by a newly isolated gordona
      strain, CYKS1 
AB  - A dibenzothiophene (DBT)-desulfurizing bacterial strain was isolated and
      identified as Gordona strain CYKS1. Strain CYKS1 was found to transform DBT to 2
      hydroxybiphenyl via the 4S pathway and to be able to also use organic sulfur
      compounds other than DBT as a sole sulfur source. Its desulfurization activity
      was susceptible to sulfate repression. Active resting cells for desulfurization
      could be prepared only in the early growth phase. When two types of diesel oils,
      middle distillate unit feed (MDUF) and light gas oil (LGO) containing various
      organic sulfur compounds including DBT, were treated with resting cells of strain
      CYKS1 for 12 h, the total sulfur content significantly decreased, from 0.15%
      (wt/wt) to 0.06% (wt/wt) for MDUF and from 0.3% (wt/wt) to 0.25% (wt/wt) for LGO.
      The newly isolated strain CYKS1 is considered to have good potential for
      application in the biodesulfurization of fossil fuels.

PMID- 9603864
TI  - Control of photosystem formation in Rhodobacter sphaeroides.

PMID- 9603866
TI  - Paradoxical enhancement of the activity of a bacterial multidrug transporter
      caused by substitutions of a conserved residue.
AB  - Substitution of threonine or serine for the evolutionary conserved intramembrane
      proline P347 of the Bacillus subtilis multidrug transporter Bmr significantly
      increases the toxin-effluxing activity of Bmr without affecting its abundance in
      the cell. In cocultivation experiments, we demonstrate that although the mutant
      T347 Bmr is advantageous to cells growing in the presence of a toxin, the wild
      type P347 Bmr is advantageous under the conditions of nutritional limitation.
      This may explain why Bmr has evolved the way it did, that is, with proline at
      position 347. These observations provide a basis for speculating that the
      evolution of Bmr has been determined by its presently unidentified natural
      function rather than by its ability to expel diverse toxins from the cell.

PMID- 9603865
TI  - FtsI and FtsW are localized to the septum in Escherichia coli.
AB  - The localization of FtsI (PBP3), a penicillin-binding protein specifically
      required for cell division in Escherichia coli, was investigated by
      immunofluorescence microscopy and found to localize to the septum. The
      localization of FtsI was not observed in ftsZ or ftsA mutants, indicating that it
      was dependent on the prior localization of these proteins. Addition of
      furazlocillin, a specific inhibitor of FtsI, prevented localization of FtsI even
      though FtsZ and FtsA localization occurred. Interestingly, the localization of
      FtsN was also prevented by furazlocillin. FtsZ displayed limited localization in
      furazlocillin-treated cells, whereas it was efficiently localized in FtsI
      depleted cells. FtsW, another essential cell division protein, was also localized
      to the septum.

PMID- 9603867
TI  - Expression of the transposase gene tnpA of Tn4652 is positively affected by
      integration host factor.
AB  - Tn4652 is a derivative of the toluene degradation transposon Tn4651 that belongs
      to the Tn3 family of transposons (M. Tsuda and T. Iino, Mol. Gen. Genet. 210:270
      276, 1987). We have sequenced the transposase gene tnpA of transposon Tn4652 and
      mapped its promoter to the right end of the element. The deduced amino acid
      sequence of tnpA revealed 96.2% identity with the putative transposase of Tn5041.
      Homology with other Tn3 family transposases was only moderate (about 20 to 24%
      identity), suggesting that Tn4652 and Tn5041 are distantly related members of the
      Tn3 family. Functional analysis of the tnpA promoter revealed that it is active
      in Pseudomonas putida but silent in Escherichia coli, indicating that some P.
      putida-specific factor is required for the transcription from this promoter.
      Additionally, tnpA promoter activity was shown to be modulated by integration
      host factor (IHF). The presence of an IHF-binding site upstream of the tnpA
      promoter enhanced the promoter activity. The positive role of IHF was also
      confirmed by the finding that the enhancing effect of IHF was not detected in the
      P. putida ihfA-deficient strain A8759. Moreover, the Tn4652 terminal sequences
      had a negative effect on transcription from the tnpA promoter in the ihfA
      defective strain. This finding suggests that IHF not only enhances transcription
      from the tnpA promoter but also alleviates the negative effect of terminal
      sequences of Tn4652 on the promoter activity. Also, an in vitro binding assay
      demonstrated that both ends of Tn4652 bind IHF from a cell lysate of E. coli.

PMID- 9603868
TI  - Enhanced secretory production of a single-chain antibody fragment from Bacillus
      subtilis by coproduction of molecular chaperones.
AB  - Formation of inclusion bodies is a major limiting factor for secretory production
      of an antidigoxin single-chain antibody (SCA) fragment from Bacillus subtilis. To
      address this problem, three new strains with enhanced production of molecular
      chaperones were constructed. WB600BHM constitutively produces the major
      intracellular molecular chaperones in an appropriate ratio without any heat shock
      treatment. This strain reduced the formation of insoluble SCA by 45% and
      increased the secretory production yield by 60%. The second strain, WB600B[pEPP],
      overproduces an extracytoplasmic molecular chaperone, PrsA. An increase in the
      total yield of SCA was observed. The third strain, WB600BHM[pEPP], coproduces
      both intracellular and extracytoplasmic molecular chaperones. This led to a
      further reduction in inclusion body formation and a 2.5-fold increase in the
      secretory production yield. SCA fragments secreted by this strain were
      biologically active and showed affinity to digoxin comparable to the affinity of
      those secreted by strains without overproduction of molecular chaperones.
      Interestingly, accumulation of a pool of periplasmic SCA was observed in the PrsA
      overproducing strains. This pool is suggested to represent the secreted folding
      intermediates in the process of achieving their final configuration.

PMID- 9603869
TI  - Effects of iron and temperature on expression of the Pseudomonas aeruginosa
      tolQRA genes: role of the ferric uptake regulator.
AB  - The tolQRA genes have been recently identified in Pseudomonas aeruginosa PAO. In
      this study, we examined the effect of iron and temperature on tolQRA expression.
      A promoterless lacZ gene was introduced downstream of plasmid-encoded tolQ and
      tolA, and expression was monitored by measuring beta-galactosidase activity of
      cultures. Addition of 25 microM FeCl3 to the culture medium reduced tolQRA
      expression by 50 to 60% in PAO but by only 25% in the fur mutant PAO A4. Northern
      hybridization analysis revealed that iron regulation occurs at the level of
      transcription and involves the P. aeruginosa ferric uptake regulator (Fur).
      Primer extension analysis was used to identify the proposed transcriptional start
      site of tolA. Although a putative Fur box was identified 20 bp upstream of the
      proposed start site, purified Fur did not bind to the tolA or tolQR promoter
      regions in an in vitro gel retardation assay. Therefore, iron regulation of the
      tol genes appears to involve an intermediate regulatory gene. Expression of tolQR
      and tolA was optimal at 37 degrees C and was reduced by 40 to 50% when cultures
      were grown at either 42 or 25 degreesC. Growth in high-iron medium at 25 degrees
      C further reduced tolQR and tolA expression.

PMID- 9603870
TI  - Purification and characterization of thin pili of IncI1 plasmids ColIb-P9 and
      R64: formation of PilV-specific cell aggregates by type IV pili.
AB  - Thin pili of the closely related IncI1 plasmids ColIb-P9 and R64 are required
      only for liquid mating and belong to the type IV family of pili. They were
      sedimented by ultracentrifugation from culture medium in which Escherichia coli
      cells harboring ColIb-P9- or R64-derived plasmids had been grown, and then the
      pili were purified by CsCl density gradient centrifugation. In negatively stained
      thin pilus samples, long rods with a diameter of 6 nm, characteristic of type IV
      pili, were observed under an electron microscope. Gel electrophoretic analysis of
      purified ColIb-P9 thin pili indicated that thin pili consist of two kinds of
      proteins, pilin and the PilV protein. Pilin was demonstrated to be the product of
      the pilS gene. Pilin was first synthesized as a 22-kDa prepilin from the pilS
      gene and subsequently processed to a 19-kDa protein by the function of the pilU
      product. The N-terminal amino group of the processed protein was shown to be
      modified. The C-terminal segments of the pilV products vary among six or seven
      different types, as a result of shufflon DNA rearrangements of the pilV gene.
      These PilV proteins were revealed to comprise a minor component of thin pili.
      Formation of PilV-specific cell aggregates by ColIb-P9 and R64 thin pili was
      demonstrated and may play an important role in liquid mating.

PMID- 9603871
TI  - Distal cleavage of 3-chlorocatechol by an extradiol dioxygenase to 3-chloro-2
      hydroxymuconic semialdehyde.
AB  - A 2,3-dihydroxybiphenyl 1,2-dioxygenase from the naphthalenesulfonate-degrading
      bacterium Sphingomonas sp. strain BN6 oxidized 3-chlorocatechol to a yellow
      product with a strongly pH-dependent absorption maximum at 378 nm. A titration
      curve suggested (de)protonation of an ionizable group with a pKa of 4.4. The
      product was isolated, purified, and converted, by treatment with diazomethane, to
      a dimethyl derivative and, by incubation with ammonium chloride, to a picolinic
      acid derivative. Mass spectra and 1H and 13C nuclear magnetic resonance (NMR)
      data for these two derivatives prove a 3-chloro-2-hydroxymuconic semialdehyde
      structure for the metabolite, resulting from distal (1,6) cleavage of 3
      chlorocatechol. 3-Methylcatechol and 2,3-dihydroxybiphenyl are oxidized by this
      enzyme, in contrast, via proximal (2,3) cleavage.

PMID- 9603872
TI  - Molecular characterization of the gene encoding the DNA gyrase A subunit of
      Streptococcus pneumoniae.
AB  - The gene encoding the DNA gyrase A subunit of Streptococcus pneumoniae was cloned
      and sequenced. The gyrA gene codes for a protein of 822 amino acids homologous to
      the gyrase A subunit of eubacteria. Translation of the gene in an Escherichia
      coli expression system revealed a 92-kDa polypeptide. A sequence-directed DNA
      curvature was identified in the promoter region of gyrA. The bend center was
      mapped and located between the -35 and -10 regions of the promoter. Primer
      extension analysis showed that gyrA transcription initiates 6 bp downstream of an
      extended -10 promoter. The possible implications of the bent DNA region as a
      regulatory element in the transcription of gyrA are discussed.

PMID- 9603873
TI  - Adaptive mutagenesis at ebgR is regulated by PhoPQ.
AB  - Adaptive mutations are mutations that occur in nondividing or very slowly
      dividing microbial cells during prolonged nonlethal selection and that are
      specific to the challenge of the selection in the sense that the only mutations
      that can be detected are those that provide a growth advantage to the cell. The
      phoPQ genes encode a two-component positively acting regulatory system that
      controls expression of at least 25 to 30 genes in Escherichia coli and Salmonella
      typhimurium. PhoPQ responds to a variety of environmental stress signals
      including Mg2+ starvation and nutritional deprivation. Here I show that
      disruption of phoP or phoQ by Tn10dCam significantly reduces the adaptive
      mutation rate to ebgR, indicating that the adaptive mutagenesis machinery is
      regulated, directly or indirectly, by phoPQ. The finding that it is regulated
      implies that adaptive mutagenesis does not simply result from a failure of
      various error correction mechanisms during prolonged starvation.

PMID- 9603874
TI  - Genes essential for nod factor production and nodulation are located on a
      symbiotic amplicon (AMPRtrCFN299pc60) in Rhizobium tropici.
AB  - Amplifiable DNA regions (amplicons) have been identified in the genome of
      Rhizobium etli. Here we report the isolation and molecular characterization of a
      symbiotic amplicon of Rhizobium tropici. To search for symbiotic amplicons, a
      cartridge containing a kanamycin resistance marker that responds to gene dosage
      and conditional origins of replication and transfer was inserted in the
      nodulation region of the symbiotic plasmid (pSym) of R. tropici CFN299.
      Derivatives harboring amplifications were selected by increasing the
      concentration of kanamycin in the cell culture. The amplified DNA region was
      mobilized into Escherichia coli and then into Agrobacterium tumefaciens. The 60
      kb symbiotic amplicon, which we termed AMPRtrCFN299pc60, contains several
      nodulation and nitrogen fixation genes and is flanked by a novel insertion
      sequence ISRtr1. Amplification of AMPRtrCFN299pc60 through homologous
      recombination between ISRtr1 repeats increased the amount of Nod factors.
      Strikingly, the conjugal transfer of the amplicon into a plasmidless A.
      tumefaciens strain confers on the transconjugant the ability to produce R.
      tropici Nod factors and to nodulate Phaseolus vulgaris, indicating that R.
      tropici genes essential for the nodulation process are confined to an ampliable
      DNA region of the pSym.

PMID- 9603875
TI  - Identification and characterization of MAE1, the Saccharomyces cerevisiae
      structural gene encoding mitochondrial malic enzyme.
AB  - Pyruvate, a precursor for several amino acids, can be synthesized from
      phosphoenolpyruvate by pyruvate kinase. Nevertheless, pyk1 pyk2 mutants of
      Saccharomyces cerevisiae devoid of pyruvate kinase activity grew normally on
      ethanol in defined media, indicating the presence of an alternative route for
      pyruvate synthesis. A candidate for this role is malic enzyme, which catalyzes
      the oxidative decarboxylation of malate to pyruvate. Disruption of open reading
      frame YKL029c, which is homologous to malic enzyme genes from other organisms,
      abolished malic enzyme activity in extracts of glucose-grown cells. Conversely,
      overexpression of YKL029c/MAE1 from the MET25 promoter resulted in an up to 33
      fold increase of malic enzyme activity. Growth studies with mutants demonstrated
      that presence of either Pyk1p or Mae1p is required for growth on ethanol. Mutants
      lacking both enzymes could be rescued by addition of alanine or pyruvate to
      ethanol cultures. Disruption of MAE1 alone did not result in a clear phenotype.
      Regulation of MAE1 was studied by determining enzyme activities and MAE1 mRNA
      levels in wild-type cultures and by measuring beta-galactosidase activities in a
      strain carrying a MAE1::lacZ fusion. Both in shake flask cultures and in carbon
      limited chemostat cultures, MAE1 was constitutively expressed. A three- to
      fourfold induction was observed during anaerobic growth on glucose. Subcellular
      fractionation experiments indicated that malic enzyme in S. cerevisiae is a
      mitochondrial enzyme. Its regulation and localization suggest a role in the
      provision of intramitochondrial NADPH or pyruvate under anaerobic growth
      conditions. However, since null mutants could still grow anaerobically, this
      function is apparently not essential.

PMID- 9603876
TI  - Posttranscriptional modifications in 16S and 23S rRNAs of the archaeal
      hyperthermophile Sulfolobus solfataricus.
AB  - Posttranscriptional modification is common to many types of RNA, but the majority
      of information concerning structure and function of modification is derived
      principally from tRNA. By contrast, less is known about modification in rRNA in
      spite of accumulating evidence for its direct participation in translation. The
      structural identities and approximate molar levels of modifications have been
      established for 16S and 23S rRNAs of the archaeal hyperthermophile Sulfolobus
      solfactaricus by using combined chromatography-mass spectrometry-based methods.
      Modification levels are exceptionally high for prokaryotic organisms, with
      approximately 38 modified sites in 16S rRNA and 50 in 23S rRNA for cells cultured
      at 75 degrees C, compared with 11 and 23 sites, respectively, in Escherichia
      coli. We structurally characterized 10 different modified nucleosides in 16S
      rRNA, 64% (24 residues) of which are methylated at O-2' of ribose, and 8 modified
      species in 23S rRNA, 86% (43 residues) of which are ribose methylated, a form of
      modification shown in earlier studies to enhance stability of the polynucleotide
      chain. From cultures grown at progressively higher temperatures, 60, 75, and 83
      degrees C, a slight trend toward increased ribose methylation levels was
      observed, with greatest net changes over the 23 degrees C range shown for 2'-O
      methyladenosine in 16S rRNA (21% increase) and for 2'-O-methylcytidine (24%) and
      2'-O-methylguanosine (22%) in 23S rRNA. These findings are discussed in terms of
      the potential role of modification in stabilization of rRNA in the thermal
      environment.

PMID- 9603877
TI  - Activation and repression of transcription at the double tandem divergent
      promoters for the xylR and xylS genes of the TOL plasmid of Pseudomonas putida.
AB  - The xylR and xylS genes are divergent and control transcription of the TOL
      plasmid catabolic pathways for toluene metabolism. Four promoters are found in
      the 300-bp intergenic region: Pr1 and Pr2 are constitutive sigma70-dependent
      tandem promoters that drive expression of xylR, while expression of the xylS gene
      is driven from Ps2, a constitutive sigma70-dependent promoter, and by the
      regulatable sigma54 class Ps1 promoter. In Ps1 the XylR targets (upstream
      activator sequences [UASs]) overlap the Pr promoters, and two sites for
      integration host factor (IHF) binding are located at the region from positions -2
      to -30 (-2/-30 region) and the -137/-156 region, the latter overlapping the Pr
      promoters. When the XylR protein binds to the UASs in the absence of effector, it
      represses expression from Pr promoters. In the XylR-plus background and in the
      absence of an effector, the level of expression from Ps1 is low, although
      detectable, whereas Ps2 is active. In this background and in the presence of an
      effector, XylR increases autorepression. In a sigma54-deficient Pseudomonas
      putida background, no expression occurred from Ps1 regardless of the presence of
      an effector. However, in the presence of an effector, the amount of RNA produced
      from Pr promoters was almost undetectable. This finding suggests that when no
      transcription occurred at the Ps1 promoter, clearance of XylR from the UASs was
      almost negligible. In this background, expression from Ps2 was very high
      regardless of the presence of an effector; this finding suggests that RNA
      polymerase containing sigma54 modulates expression from the downstream Ps2
      sigma70-dependent promoter. In a P. putida IHF-minus background and in the
      presence of effector, Ps1 expression was the highest found; in contrast, the
      basal levels of this promoter were the lowest observed. This finding suggests
      that IHF acts in vivo as a repressor of the sigma54-dependent Ps1 promoter. In an
      IHF-deficient host background, expression from Ps2 in the presence of effector
      was negligible. Thus, binding of RNA polymerase containing sigma54 at the
      upstream promoter may modulate expression from the Ps2 promoter.

PMID- 9603878
TI  - Nonnative proteins induce expression of the Bacillus subtilis CIRCE regulon.
AB  - The chaperone-encoding groESL and dnaK operons constitute the CIRCE regulon of
      Bacillus subtilis. Both operons are under negative control of the repressor
      protein HrcA, which interacts with the CIRCE operator and whose activity is
      modulated by the GroESL chaperone machine. In this report, we demonstrate that
      induction of the CIRCE regulon can also be accomplished by ethanol stress and
      puromycin. Introduction of the hrcA gene and a transcriptional fusion under the
      control of the CIRCE operator into Escherichia coli allowed induction of this
      fusion by heat shock, ethanol stress, and overproduction of GroESL substrates.
      The expression level of this hrcA-bgaB fusion inversely correlated with the
      amount of GroE machinery present in the cells. Therefore, all inducing conditions
      seem to lead to induction via titration of the GroE chaperonins by the increased
      level of nonnative proteins formed. Puromycin treatment failed to induce the
      sigmaB-dependent general stress regulon, indicating that nonnative proteins in
      general do not trigger this response. Reconstitution of HrcA-dependent heat shock
      regulation of B. subtilis in E. coli and complementation of E. coli groESL
      mutants by B. subtilis groESL indicate that the GroE chaperonin systems of the
      two bacterial species are functionally exchangeable.

PMID- 9603879
TI  - Evidence for a conjugation-like mechanism of DNA transfer in Helicobacter pylori.
AB  - Many strains of Helicobacter pylori are naturally competent for transformation in
      vitro. Since there is a high degree of genetic variation among H. pylori strains,
      we sought to determine whether mechanisms of DNA exchange other than
      transformation exist in these organisms. Studies were done with H. pylori cells
      that each were resistant to two different antibiotics; the procedure used
      involved mating of cells on plates or in broth, in the absence or presence of
      DNase. In each experiment, such matings produced progeny with the markers of both
      parents. Examination of the full resistance profile and random arbitrarily primed
      DNA PCR (RAPD-PCR) profiles of the progeny indicated that DNA transfer was
      bidirectional. DNase treatment reduced but did not eliminate transfer; only the
      presence of both DNase and a membrane separating the cells did so. For progeny
      derived from matings in the presence of DNase, antibiotic resistance and RAPD
      profiles indicated that transfer was unidirectional. DNase-treated cell-free
      supernatants also did not transform, ruling out transduction. These experiments
      indicate that both a DNase-sensitive mechanism (transformation) and a DNase
      resistant conjugation-like mechanism involving cell-to-cell contact may
      contribute to DNA transfer between H. pylori cells.

PMID- 9603880
TI  - DNA synthesis and viability of a mutT derivative of Escherichia coli WP2 under
      conditions of amino acid starvation and relation to stationary-phase (adaptive)
      mutation.
AB  - Escherichia coli WP2 bacteria with an ochre amino acid auxotrophy show no
      evidence of growth during the first few days after plating at densities above
      10(8) on plates lacking the required amino acid. They lose viability for some
      days, and then a subpopulation recovers and there is cell turnover. At very low
      plating densities (around 10(2) per plate), almost every cell will eventually
      form a small but visible colony. At intermediate plating densities (10(6) to
      10(7) per plate), there is an immediate increase in the number of viable
      bacteria. The results are consistent with a model that assumes that growth is
      dependent on trace amounts of tryptophan or a tryptophan-complementing substance
      and that death is due to extracellular toxic species in the medium, including
      active oxygen species. Mutations in mutT bacteria under these conditions result
      from incorporation of 7,8-dihydro-8-oxo-dGTP into DNA and thus largely reflect
      DNA synthesis associated with the increase in the number of viable cells at the
      initial density used (10(7) per plate). We show that the increase in cell number
      and much of this DNA synthesis can be eliminated by the presence of 10(8)
      scavenger bacteria and by removal of early-arising mutant colonies that release
      the required amino acid. The synthesis that remains is equivalent to less than a
      quarter of a genome per day and is marginally reduced, if at all, in a polA
      derivative. We cannot exclude the possibility that this residual DNA synthesis is
      peculiar to mutT bacteria due to transcriptional leakiness, although there is no
      evidence that this is a major problem in this strain. If such DNA synthesis also
      occurs in wild-type bacteria, it may well be important for adaptive mutation
      since use of a more refined agar in selective plates both eliminated the initial
      increase in cell number seen at low density (10(7) per plate) and reduced the
      rate of appearance of mutants at plating densities above 10(8) per plate.

PMID- 9603881
TI  - glkA is involved in glucose repression of chitinase production in Streptomyces
      lividans.
AB  - Chitinase production in Streptomyces lividans is induced by chitin and repressed
      in the presence of glucose. A mutant of S. lividans TK24, strain G015, which was
      defective in glucose repression of chitinase production, was obtained by
      screening colonies for zones of clearing on colloidal chitin agar plates
      containing 1.0% (wt/vol) glucose. The transcriptional analysis of chiA in G015
      with xylE, which encodes catechol 2,3-dioxygenase, as a reporter gene showed that
      the transcription from the chiA promoter of S. lividans TK24 occurred regardless
      of the presence of glucose. G015 was resistant to 2-deoxyglucose (2-DOG) and did
      not utilize glucose as a sole carbon source. When a DNA fragment containing glkA,
      a gene for glucose kinase, of Streptomyces coelicolor A3(2) was introduced into
      strain G015 on a low-copy-number plasmid, the sensitivity to 2-DOG, the ability
      to utilize glucose, and the glucose repression of chitinase production were
      restored. These results indicate that glkA is involved in glucose repression of
      chitinase production in S. lividans TK24.

PMID- 9603882
TI  - Characterization of the hca cluster encoding the dioxygenolytic pathway for
      initial catabolism of 3-phenylpropionic acid in Escherichia coli K-12.
AB  - We have identified, cloned, and sequenced the hca cluster encoding the
      dioxygenolytic pathway for initial catabolism of 3-phenylpropionic acid (PP) in
      Escherichia coli K-12. This cluster maps at min 57.5 of the chromosome and is
      composed of five catabolic genes arranged as a putative operon (hcaA1A2CBD) and
      two additional genes transcribed in the opposite direction that encode a
      potential permease (hcaT) and a regulator (hcaR). Sequence comparisons revealed
      that while hcaA1A2CD genes encode the four subunits of the 3-phenylpropionate
      dioxygenase, the hcaB gene codes for the corresponding cis-dihydrodiol
      dehydrogenase. This type of catabolic module is homologous to those encoding
      class IIB dioxygenases and becomes the first example of such a catabolic cluster
      in E. coli. The inducible expression of the hca genes requires the presence of
      the hcaR gene product, which acts as a transcriptional activator and shows
      significant sequence similarity to members of the LysR family of regulators.
      Interestingly, the HcaA1A2CD and HcaB enzymes are able to oxidize not only PP to
      3-(2,3-dihydroxyphenyl)propionate (DHPP) but also cinnamic acid (CI) to its
      corresponding 2, 3-dihydroxy derivative. Further catabolism of DHPP requires the
      mhp-encoded meta fission pathway for the mineralization of 3
      hydroxyphenylpropionate (3HPP) (A. Ferrandez, J. L. Garcia, and E. Diaz, J.
      Bacteriol. 179:2573-2581, 1997). Expression in Salmonella typhimurium of the mhp
      genes alone or in combination with the hca cluster allowed the growth of the
      recombinant bacteria in 3-hydroxycinnamic acid (3HCI) and CI, respectively. Thus,
      the convergent mhp- and hca-encoded pathways are also functional in S.
      typhimurium, and they are responsible for the catabolism of different
      phenylpropanoid compounds (3HPP, 3HCI, PP, and CI) widely available in nature.

PMID- 9603884
TI  - Novel temperature-sensitive mutants of Escherichia coli that are unable to grow
      in the absence of wild-type tRNA6Leu.
AB  - Escherichia coli has only a single copy of a gene for tRNA6Leu (Y. Komine et al.,
      J. Mol. Biol. 212:579-598, 1990). The anticodon of this tRNA is CAA (the wobble
      position C is modified to O2-methylcytidine), and it recognizes the codon UUG.
      Since UUG is also recognized by tRNA4Leu, which has UAA (the wobble position U is
      modified to 5-carboxymethylaminomethyl-O2-methyluridine) as its anticodon,
      tRNA6Leu is not essential for protein synthesis. The BT63 strain has a mutation
      in the anticodon of tRNA6Leu with a change from CAA to CUA, which results in the
      amber suppressor activity of this strain (supP, Su+6). We isolated 18 temperature
      sensitive (ts) mutants of the BT63 strain whose temperature sensitivity was
      complemented by introduction of the wild-type gene for tRNA6Leu. These tRNA6Leu
      requiring mutants were classified into two groups. The 10 group I mutants had a
      mutation in the miaA gene, whose product is involved in a modification of tRNAs
      that stabilizes codon-anticodon interactions. Overexpression of the gene for
      tRNA4Leu restored the growth of group I mutants at 42 degrees C. Replacement of
      the CUG codon with UUG reduced the efficiency of translation in group I mutants.
      These results suggest that unmodified tRNA4Leu poorly recognizes the UUG codon at
      42 degreesC and that the wild-type tRNA6Leu is required for translation in order
      to maintain cell viability. The mutations in the six group II mutants were
      complemented by introduction of the gidA gene, which may be involved in cell
      division. The reduced efficiency of translation caused by replacement of the CUG
      codon with UUG was also observed in group II mutants. The mechanism of
      requirement for tRNA6Leu remains to be investigated.

PMID- 9603883
TI  - Cascade regulation of dimethyl sulfoxide reductase (dor) gene expression in the
      facultative phototroph Rhodobacter sphaeroides 2.4.1T.
AB  - Under anaerobic-dark growth conditions, in the presence of the alternative
      electron acceptor dimethyl sulfoxide (DMSO) or trimethylamine N-oxide (TMAO),
      Rhodobacter sphaeroides 2.4.1(T) respires anaerobically using the molybdoenzyme
      DMSO reductase (DMSOR). Genes encoding DMSOR and associated proteins are encoded
      by genes of the dor locus. Previously, we demonstrated that the expression of
      DMSOR is regulated by both the oxygen status of the cell via the FnrL protein and
      by the presence of DMSO or TMAO, presumably through the DorS-DorR two-component
      sensor-regulator system. Here we further investigate expression of the dor genes
      through the use of transcriptional lacZ fusions to the dorS, dorR, and dorC
      promoters. The expression of dorC::lacZ was strongly induced by the absence of
      oxygen and presence of DMSO. In accordance with our previous findings of DMSOR
      activity, dorC::lacZ expression was reduced by up to one-third when cells were
      grown photosynthetically in the presence of DMSO with medium or high light,
      compared to the expression observed after anaerobic-dark growth. The induction of
      dorC::lacZ expression in the presence of DMSO was dependent on the DorS and DorR
      proteins. Expression of the dorS and dorR genes was also induced in the absence
      of oxygen. In an FnrL mutant, dorS::lacZ expression was not induced when oxygen
      tensions in the media were lowered, in contrast to what occurred in the wild-type
      strain. The expression of dorS::lacZ and dorR::lacZ was dependent on the DorS and
      DorR proteins themselves, suggesting the importance of autoregulation. These
      results demonstrate a cascade regulation of dor gene expression, where the
      expression of the regulatory proteins DorS and DorR governs the downstream
      regulation of the dorCBA operon encoding the structural proteins of DMSOR.

PMID- 9603885
TI  - Translation of the flagellar gene fliO of Salmonella typhimurium from putative
      tandem starts.
AB  - The flagellar gene fliO of Salmonella typhimurium can be translated from an AUG
      codon that overlaps the termination codon of fliN (K. Ohnishi et al., J.
      Bacteriol. 179:6092-6099, 1997). However, it had been concluded on the basis of
      complementation analysis that in Escherichia coli a second start codon 60 bp
      downstream was the authentic one (J. Malakooti et al., J. Bacteriol. 176:189-197,
      1994). This raised the possibility of tandem translational starts, such as occur
      for the chemotaxis gene cheA; this possibility was increased by the existence of
      a stem-loop sequence covering the second start, a feature also found with cheA.
      Protein translated from the first start codon was detected regardless of whether
      the second start codon was present; it was also detected when the stem-loop
      structure was disrupted or deleted. Translation from the second start codon,
      either as the natural one (GUG) or as AUG, was not detected when the first start
      and intervening sequence were intact. Nor was it detected when the first codon
      was attenuated (by conversion of AUGAUG to AUAAUA; in S. typhimurium there is a
      second, adjacent, AUG) or eliminated (by conversion to CGCCGC); disruption of the
      stem-loop structure still did not yield detectable translation from the second
      start. When the entire sequence up to the second start was deleted, translation
      from the second start was detected provided the natural codon GUG had been
      converted to AUG. A fliO null mutant could be fully complemented in swarm assays
      whenever the first start and intervening sequence were present, regardless of the
      state of the second start. Reasonably good complementation occurred when the
      first start and intervening sequence were absent provided the second start was
      intact, either as AUG or as GUG; thus translation from the GUG codon must have
      been occurring even though protein levels were too low to be detected. The
      translated intervening sequence is rather divergent between S. typhimurium and E.
      coli and corresponds to a substantial cytoplasmic domain prior to the sole
      transmembrane segment, which is highly conserved; the sequence following the
      second start begins immediately prior to that transmembrane segment. The
      significance of the data for FliO is discussed and compared to the equivalent
      data for CheA. Attention is also drawn to the fact that given an optimal ribosome
      binding site, AUA can serve as a fairly efficient start codon even though it
      seldom if ever appears to be used in nature.

PMID- 9603886
TI  - Mutational analysis of the TnrA-binding sites in the Bacillus subtilis nrgAB and
      gabP promoter regions.
AB  - Transcription of the Bacillus subtilis nrgAB promoter is activated during
      nitrogen-limited growth by the TnrA protein. A common inverted repeat,
      TGTNAN7TNACA (TnrA site), is centered 49 to 51 bp upstream of the transcriptional
      start sites for the TnrA-regulated nrgAB, gabP P2, and nas promoters.
      Oligonucleotide-directed mutagenesis of the nrgAB promoter region showed that
      conserved nucleotides within the TnrA site, the A+T-rich region between the two
      TnrA half-sites, and an upstream A tract are all required for high-level
      activation of nrgAB expression. Mutations that alter the relative distance
      between the two half-sites of the nrgAB TnrA site abolish nitrogen regulation of
      nrgAB expression. Spacer mutations that change the relative distance between the
      TnrA site and -35 region of the nrgAB promoter reveal that activation of nrgAB
      expression occurs only when the TnrA site is located 49 to 51 bp upstream of the
      transcriptional start site. Mutational analysis of the conserved nucleotides in
      the gabP P2 TnrA site showed that this sequence is also required for nitrogen
      regulated gabP P2 expression. The TnrA protein, expressed in an overproducing
      Escherichia coli strain, had a 625-fold-higher affinity for the wild-type nrgAB
      promoter DNA than for a mutated nrgAB promoter DNA fragment that is unable to
      activate nrgAB expression in vivo. These results indicate that the proposed TnrA
      site functions as the binding site for the TnrA protein. TnrA was found to
      activate nrgAB expression during late exponential growth in nutrient sporulation
      medium containing glucose, suggesting that cells become nitrogen limited during
      growth in this medium.

PMID- 9603887
TI  - D-Alanylcardiolipin, a major component of the unique lipid pattern of Vagococcus
      fluvialis.
AB  - Motile group N streptococci, classified as Vagococcus fluvialis, have been
      isolated from cows' udders, human and animal feces, river water, and seawater.
      They possess an unusual membrane lipid and fatty acid pattern. We isolated and
      characterized 13 polar lipids, 8 of them also found in other gram-positive
      bacteria: mono- and dihexosyldiacylglycerol, an acylated and a glycerophosphate
      substituted derivative of the latter, cardiolipin, phosphatidylglycerol, D
      alanylphosphatidylglycerol, and L-lysylphosphatidylglycerol. Besides them, we
      characterized two rare compounds, bis(acylglycero)phosphate and alpha-D
      glucopyranosylcardiolipin, and two compounds so far not detected in nature, D
      alanylbis(acylglycero)phosphate and D-alanylcardiolipin. The concomitant
      occurrence of four aminoacyl phospholipids in one organism is another unique
      finding. Substituted cardiolipins represent a novel lipid class: in vagococci, D
      alanylcardiolipin is a major membrane lipid component, contributing 11 and 26
      mol% of total lipids in the exponential and stationary phases of growth,
      respectively. The vagococcal lipids contain even-numbered straight-chain
      saturated and cis-monounsaturated fatty acids, but the cis-monoenic acids belong
      to the omega-9 series and not the omega-7 series, found in enterococci,
      lactococci, and streptococci.

PMID- 9603888
TI  - A regulatory mutant of Hansenula polymorpha exhibiting methanol utilization
      metabolism and peroxisome proliferation in glucose.
AB  - Mutant LGM-128 of Hansenula polymorpha harbors the recessive mutation glr2-1
      which confers a complex pleiotropic phenotype, the major feature of which is the
      metabolically unnecessary induction of methanol utilization metabolism (C1
      metabolism) during growth on glucose, whether or not methanol is in the medium.
      Therefore, in this mutant, peroxisomes are formed and proliferate upon
      cultivation in glucose-containing media. In these media, LGM-128 shows induction
      levels of C1 metabolism that are similar to those observed in methanol-containing
      media. This indicates that GLR2 controls the repression-derepression process
      stimulated by glucose and that the induction process triggered by methanol plays
      only a minor role in activating C1 metabolism. Cultivating LGM-128 in methanol
      and then transferring it to glucose media revealed that active degradative
      processes occur, leading to the disappearance of C1 metabolism. This observation
      suggests that, although stimulated by glucose, the two processes are controlled
      by elements which are, at least in part, distinct. Finally, glr2-1 does not
      affect ethanol repression, suggesting that in H. polymorpha the two repressing
      circuits are separated.

PMID- 9603889
TI  - A spore coat protein, CotS, of Bacillus subtilis is synthesized under the
      regulation of sigmaK and GerE during development and is located in the inner coat
      layer of spores.
AB  - The spore coat of Bacillus subtilis has a unique morphology and consists of
      polypeptides of different sizes, whose synthesis and assembly are precisely
      regulated by a cascade of transcription factors and regulatory proteins. We
      examined the factors that regulate cotS gene expression and CotS assembly into
      the coat layer of B. subtilis by Northern blot and Western blot analysis.
      Transcription of cotS mRNA was not detected in sporulating cells of sigmaK and
      gerE mutants by Northern blot analysis. By Western blot analysis using anti-CotS
      antibody, CotS was first detected in protein samples solubilized from wild-type
      cells at 5 h after the start of sporulation. CotS was not detected in the
      vegetative cells and spores of a gerE mutant or in the spores of mutants
      deficient in sigmaE, sigmaF, sigmaG, or sigmaK. CotS was detected in the
      sporangium but not in the spores of a cotE mutant. The sequence of the promoter
      region of cotS was similar to the consensus sequences for binding of sigmaK and
      GerE. These results demonstrate that sigmaK and GerE are required for cotS
      expression and that CotE is essential for the assembly of CotS in the coat.
      Immunoelectron microscopic observation using anti-CotS antibody revealed that
      CotS is located within the spore coat, in particular in the inner coats of
      dormant spores.

PMID- 9603890
TI  - Phylogeny of dissimilatory sulfite reductases supports an early origin of sulfate
      respiration.
AB  - Microorganisms that use sulfate as a terminal electron acceptor for anaerobic
      respiration play a central role in the global sulfur cycle. Here, we report the
      results of comparative sequence analysis of dissimilatory sulfite reductase (DSR)
      genes from closely and distantly related sulfate-reducing organisms to infer the
      evolutionary history of DSR. A 1.9-kb DNA region encoding most of the alpha and
      beta subunits of DSR could be recovered only from organisms capable of
      dissimilatory sulfate reduction with a PCR primer set targeting highly conserved
      regions in these genes. All DNA sequences obtained were highly similar to one
      another (49 to 89% identity), and their inferred evolutionary relationships were
      nearly identical to those inferred on the basis of 16S rRNA. We conclude that the
      high similarity of bacterial and archaeal DSRs reflects their common origin from
      a conserved DSR. This ancestral DSR was either present before the split between
      the domains Bacteria, Archaea, and Eucarya or laterally transferred between
      Bacteria and Archaea soon after domain divergence. Thus, if the physiological
      role of the DSR was constant over time, then early ancestors of Bacteria and
      Archaea already possessed a key enzyme of sulfate and sulfite respiration.

PMID- 9603891
TI  - Escherichia coli clone Sonnei (Shigella sonnei) had a chromosomal O-antigen gene
      cluster prior to gaining its current plasmid-borne O-antigen genes.
AB  - O antigen is part of the lipopolysaccharide present in the outer membrane of gram
      negative bacteria. The surface-exposed O antigen is subject to selection by the
      host immune system, which may account for the maintenance of many different O
      antigen forms. Characteristically, all genes specific to O-antigen synthesis are
      clustered in a region close to the his and gnd genes on the chromosome of
      Escherichia coli and related species. Shigella sonnei, essentially a clone of E.
      coli (E. coli clone Sonnei), is an important human pathogen and is unusual in
      that its O-antigen gene cluster is located on a plasmid. Our results suggest that
      it once had a normal chromosomal O-antigen gene cluster which has been largely
      deleted. We suggest that the O antigen encoded by the plasmid-borne genes offered
      a selective advantage in adapting to a new environment and that the chromosomal O
      antigen genes were eventually inactivated. We also identified, by PCR and
      sequencing, a potential ancestor of E. coli Sonnei among the 166 known E. coli
      serotype strains.

PMID- 9603893
TI  - Determining the optimal thymidine concentration for growing Thy- Escherichia coli
      strains.
AB  - Changes of thymidine concentration in the growth medium affect the chromosome
      replication time of Thy- strains without at the same time causing a detectable
      difference in the growth rate (R. H. Pritchard and A. Zaritsky, Nature 226:126
      131, 1970). Consequently, the optimal thymidine concentration cannot be
      determined by ascertaining which concentration produces the highest growth rate.
      Here we present a method for determining the optimal thymidine concentration of
      any Thy- Escherichia coli strain. Using this method, we found that the E. coli
      "wild-type" strain MG1655 has a partial Thy- phenotype.

PMID- 9603892
TI  - Role of the multidrug efflux systems of Pseudomonas aeruginosa in organic solvent
      tolerance.
AB  - Multidrug efflux pumps with a broad substrate specificity make a major
      contribution to intrinsic and acquired multiple antibiotic resistance in
      Pseudomonas aeruginosa. Using genetically defined efflux pump mutants, we
      investigated the involvement of the three known efflux systems, MexA-MexB-OprM,
      MexC-MexD-OprJ, and MexE-MexF-OprN, in organic solvent tolerance in this
      organism. Our results showed that all three systems are capable of providing some
      level of tolerance to organic solvents such as n-hexane and p-xylene. Expression
      of MexAB-OprM was correlated with the highest levels of tolerance, and indeed,
      this efflux system was a major contributor to the intrinsic solvent tolerance of
      P. aeruginosa. Intrinsic organic solvent tolerance was compromised by a
      protonophore, indicating that it is substantially energy dependent. These data
      suggest that the efflux of organic solvents is a factor in the tolerance of P.
      aeruginosa to these compounds and that the multidrug efflux systems of this
      organism can accommodate organic solvents, as well as antibiotics.

PMID- 9603894
TI  - Multidrug resistance following expression of the Escherichia coli marA gene in
      Mycobacterium smegmatis.
AB  - Expression of the Escherichia coli multiple antibiotic resistance marA gene
      cloned in Mycobacterium smegmatis produced increased resistance to multiple
      antimicrobial agents, including rifampin, isoniazid, ethambutol, tetracycline,
      and chloramphenicol. Cloned marR or marA cloned in the antisense direction had no
      effect. Resistance changes were lost with spontaneous loss of the plasmid bearing
      marA. A MarA mutant protein, having an insertional mutation within either of its
      two alpha-helices of the first putative helix-turn-helix domain, failed to
      produce the multiresistance phenotype in E. coli and M. smegmatis, indicating
      that this region is critical for MarA function. These results strongly suggest
      that E. coli marA functions in M. smegmatis and that a mar-like regulatory system
      exists in this organism.

PMID- 9603895
TI  - In vitro synthesis of multicopy single-stranded DNA, using separate primer and
      template RNAs, by Escherichia coli reverse transcriptase.
AB  - A minor population of wild strains of Escherichia coli contains a retron, a
      retroelement responsible for the synthesis of multicopy single-stranded DNA
      (msDNA). The retron is a genetic element consisting of the gene for reverse
      transcriptase (RT) and the msr-msd region under a single promoter. A single RNA
      transcript from the msr-msd region serves not only as a template but also as a
      primer for msDNA synthesis. Here, using a cell-free system with purified RT from
      retron Ec73, we examined whether the reaction can occur in a bimolecular reaction
      with use of separately expressed msr and msd transcripts. DNA sequencing of the
      cell-free product revealed that the sequence of the 5'-end region was identical
      to that of msDNA-Ec73, indicating that the cDNA synthesis was primed from the 2'
      OH group of the specific internal G residue of the primer RNA, identical to the
      branching G residue in the RNA molecule of msDNA-Ec73. The present results raise
      an intriguing possibility for a role of bacterial retrons in vivo, the
      possibility that cellular mRNAs can be converted into cDNAs in retron-harboring
      cells if the mRNAs contain a sequence complementary to the sequence directly
      upstream of the branching G residue of the msr RNA transcript.

PMID- 9603896
TI  - Characterization of chemotactic responses and flagella of Hyphomicrobium strain
      W1-1B.
AB  - Motile swarmer cells of Hyphomicrobium strain W1-1B displayed positive
      chemotactic responses toward methylamine, dimethylamine, and trimethylamine but
      did not display significant chemotactic responses towards methanol and arginine.
      Electron micrographs of negatively stained intact flagellar filaments indicated a
      novel striated surface pattern. The flagella were composed of two proteins of 39
      and 41 kDa. Neither protein was a glycoprotein as determined by Schiff's staining
      and by enzyme immunoassay. Protein fingerprints visualized from silver-stained
      polyacrylamide gels and Western blots of protease-digested samples indicated that
      the two proteins were similar but not identical. Monoclonal antibodies prepared
      to the complex flagella of Rhizobium meliloti cross-reacted with the striated
      flagella of Hyphomicrobium strain W1-1B; however, these antibodies did not cross
      react with smooth-surface flagella. These results suggest that complex and
      striated flagella possess homologous epitope regions.

PMID- 9603897
TI  - A Tn7-like transposon is present in the glmUS region of the obligately
      chemoautolithotrophic bacterium Thiobacillus ferrooxidans.
AB  - The region downstream of the Thiobacillus ferrooxidans ATCC 33020 atp operon was
      examined, and the genes encoding N-acetylglucosamine-1-uridyltransferase (glmU)
      and glucosamine synthetase (glmS) were found. This atpEFHAGDC-glmUS gene order is
      identical to that of Escherichia coli. The T. ferrooxidans glmS gene was shown to
      complement E. coli glmS mutants for growth on minimal medium lacking glucosamine.
      A Tn7-like transposon, Tn5468, was found inserted into the region immediately
      downstream of the glmS gene in a manner similar to the site-specific insertion of
      transposon Tn7 within the termination region of the E. coli glmS gene. Tn5468 was
      sequenced, and Tn7-like terminal repeat sequences as well as several open reading
      frames which are related to the Tn7 transposition genes tnsA, tnsB, tnsC, and
      tnsD were found. Tn5468 is the closest relative of Tn7 to have been characterized
      to date. Southern blot hybridization indicated that a similar or identical
      transposon was present in three T. ferrooxidans strains isolated from different
      parts of the world but not in two Thiobacillus thiooxidans strains or a
      Leptospirillum ferrooxidans strain. Since T. ferrooxidans is an obligately
      acidophilic autotroph and E. coli is a heterotroph, ancestors of the Tn7-like
      transposons must have been active in a variety of physiologically different
      bacteria so that their descendants are now found in bacteria that occupy very
      different ecological niches.

PMID- 9603898
TI  - Analysis of cis-acting elements required for bfpA expression in enteropathogenic
      Escherichia coli.
AB  - bfpA expression in enteropathogenic Escherichia coli is regulated by growth
      medium, temperature, and ammonium concentration and requires the BfpT protein
      (also called PerA), a member of the AraC family of transcriptional activators.
      Site-directed and PCR random mutagenesis, as well as deletion analysis of the
      bfpA upstream regulatory region, supported assignment of the promoter elements
      and demonstrated that the cis-acting elements that mediate BfpT-dependent
      regulation of bfpA are located between positions -85 and -46. Interestingly, this
      region shares 73% identity with a 40-bp-long AT-rich tract located upstream of
      the bfpT gene, which is essential for bfpT autoregulation.

PMID- 9603899
TI  - Activation and repression of transcription by differential contact: two sides of
      a coin.

PMID- 9603900
TI  - The activation of glycogen synthase by insulin switches from kinase inhibition to
      phosphatase activation during adipogenesis in 3T3-L1 cells.
AB  - The effects of insulin and platelet-derived growth factor (PDGF) on glycogen
      synthase activation were compared in 3T3-L1 fibroblasts and adipocytes. In the
      fibroblasts, PDGF elicited a stronger phosphorylation of mitogen-activated
      protein kinase (MAPK) and AKT than did insulin. Both agents caused a comparable
      stimulation of receptor autophosphorylation, MAPK, and phosphatidylinositol 3
      kinase (PI3-K) activation in the adipocytes. However, adipogenesis resulted in
      the uncoupling of PI3-K activation by PDGF from subsequent AKT phosphorylation.
      The relative contributions of glycogen synthase kinase-3 (GSK-3) inactivation and
      protein phosphatase-1 (PP1) activation in the regulation of glycogen synthase in
      both cell types were evaluated. Insulin and PDGF caused a small increase in
      glycogen synthase a activity in the fibroblasts. Additionally, both agents caused
      a similar inhibition of GSK-3, while having no effect on PP1 activity. Following
      differentiation, insulin treatment resulted in a 5-fold stimulation of glycogen
      synthase, whereas PDGF was without effect. Both agents caused a comparable
      inhibition of GSK-3 activity in the adipocytes, whereas only insulin activated
      PP1. Finally, wortmannin completely blocked the stimulation of PP1 by insulin in
      3T3-L1 adipocytes, indicating that PI3-K inhibition can impinge on PP1
      activation. Cumulatively these results suggest that the weak activation of
      glycogen synthase in 3T3-L1 fibroblasts is mediated by GSK-3 inactivation,
      whereas in the more metabolically active adipocytes, the insulin-specific
      activation of glycogen synthase is mediated by PP1 activation.

PMID- 9603901
TI  - Functional coupling of phosphatidylinositol 4,5-bisphosphate to inositol 1,4,5
      trisphosphate receptor.
AB  - The inositol 1,4,5-trisphosphate receptor (InsP3R) plays a key role in
      intracellular Ca2+ signaling. InsP3R is activated by InsP3 produced from
      phosphatidylinositol 4,5-bisphosphate (PIP2) by phospholipase C cleavage. Using
      planar lipid bilayer reconstitution technique, we demonstrate here that rat
      cerebellar InsP3R forms a stable inhibitory complex with endogenous PIP2.
      Disruption of InsP3R-PIP2 interaction by specific anti-PIP2 monoclonal antibody
      resulted in 3-4-fold increase in InsP3R activity and 10-fold shift in apparent
      affinity for InsP3. Exogenously added PIP2 blocks InsP3 binding to InsP3R and
      inhibits InsP3R activity. Similar results were obtained with a newly synthesized
      water soluble analog of PIP2, dioctanoyl-(4,5)PIP2, indicating that insertion of
      PIP2 into membrane is not required to exert its inhibitory effects on the InsP3R.
      We hypothesize that the functional link between InsP3R and PIP2 described in the
      present report provides a basis for a local, rapid, and efficient coupling
      between phospholipase C activation, PIP2 hydrolysis, and intracellular Ca2+ wave
      initiation in neuronal and non-neuronal cells.

PMID- 9603902
TI  - Helicobacter pylori generates superoxide radicals and modulates nitric oxide
      metabolism.
AB  - During studies of the bactericidal action of nitric oxide (NO), we found that it
      reversibly inhibited the respiration of Escherichia coli and irreversibly
      inhibited the respiration of Helicobacter pylori. Peroxynitrite, a reaction
      product of NO and superoxide, irreversibly inhibited the respiration of both H.
      pylori and E. coli. H. pylori, but not E. coli, generated substantial amounts of
      superoxide radicals. These results suggest that NO directly inhibits the
      respiration of E. coli whereas it rapidly reacts with endogenously generated
      superoxide radicals in H. pylori. The resulting peroxynitrite inactivates the
      respiration of H. pylori.

PMID- 9603903
TI  - Monoamine oxidase contains a redox-active disulfide.
AB  - Mitochondrial monoamine oxidases A and B (MAO A and MAO B) are ubiquitous
      homodimeric FAD-containing oxidases that catalyze the oxidation of biogenic
      amines. Both enzymes play a vital role in the regulation of neurotransmitter
      levels in brain and are of interest as drug targets. However, little is known
      about the amino acid residues involved in the catalysis. The experiments reported
      here show that both MAO A and MAO B contain a redox-active disulfide at the
      catalytic center. The results imply that MAO may be a novel type of disulfide
      oxidoreductase and open the way to characterizing the catalytic and chemical
      mechanism of the enzyme.

PMID- 9603904
TI  - The vacB gene required for virulence in Shigella flexneri and Escherichia coli
      encodes the exoribonuclease RNase R.
AB  - vacB, a gene previously shown to be required for expression of virulence in
      Shigella and enteroinvasive Escherichia coli, has been found to encode the 3'-5'
      exoribonuclease, RNase R. Thus, cloning of E. coli vacB led to overexpression of
      RNase R activity, and partial deletion or interruption of the cloned gene
      abolished this overexpression. Interruption of the chromosomal copy of vacB
      eliminated endogenous RNase R activity; however, the absence of RNase R by itself
      had no effect on cell growth. In contrast, cells lacking both RNase R and
      polynucleotide phosphorylase were found to be inviable. These data indicate that
      RNase R participates in an essential cell function in addition to its role in
      virulence. The identification of the vacB gene product as RNase R should aid in
      understanding how the virulence phenotype in enterobacteria is expressed and
      regulated. On the basis of this information we propose that vacB be renamed rnr.

PMID- 9603905
TI  - A type II phosphoinositide 3-kinase is stimulated via activated integrin in
      platelets. A source of phosphatidylinositol 3-phosphate.
AB  - We have observed that aggregation of human platelets, caused by activation of
      integrin alphaIIb beta3 and its consequent binding of fibrinogen, stimulates a
      novel pathway for synthesis of phosphatidylinositol 3,4bisphosphate, thereby
      activating protein kinase B/Akt. Such synthesis depends upon both the generation
      of phosphatidylinositol 3-phosphate (PtdIns3P), which is sensitive to wortmannin
      (IC50 7 nM) and calpain inhibitors, and the phosphorylation of PtdIns3P by
      PtdIns3P 4-kinase. We now report that a recently characterized C2 domain
      containing phosphoinositide 3-kinase isoform (HsC2-PI3K) is present in platelets
      and a leukemic cell line (CHRF-288) derived from megakaryoblasts, and is likely
      to be responsible for the stimulated synthesis of PtdIns3P observed in platelets.
      HsC2-PI3K, identifiable by Western blotting and immunoprecipitatable activity, is
      sensitive to wortmannin (IC50 6-10 nM), requires Mg2+, and shows strong
      preference for PtdIns over PtdIns4P or phosphatidylinositol 4,5-bisphosphate as
      substrate. HsC2-PI3K is activated severalfold when platelets aggregate in an
      alphaIIb beta3-dependent manner or when platelet or CHRF-288 lysates are
      incubated with Ca2+. Activation is prevented by calpain inhibitors. CHRF-288,
      which cannot undergo activation of alphaIIb beta3 and thereby aggregate in
      response to platelet agonists, do not generate PtdIns3P or activate HsC2-PI3K
      under conditions that stimulate other phosphoinositide 3-kinases. HsC2-PI3K may
      thus be an important effector for integrin-dependent signaling.

PMID- 9603906
TI  - Inactivation of human manganese-superoxide dismutase by peroxynitrite is caused
      by exclusive nitration of tyrosine 34 to 3-nitrotyrosine.
AB  - Peroxynitrite has recently been implicated in the inactivation of many enzymes.
      However, little has been reported on the structural basis of the inactivation
      reaction. This study proposes that nitration of a specific tyrosine residue is
      responsible for inactivation of recombinant human mitochondrial manganese
      superoxide dismutase (Mn-SOD) by peroxynitrite. Mass spectroscopic analysis of
      the peroxynitrite-inactivated Mn-SOD showed an increased molecular mass because
      of a single nitro group substituted onto a tyrosine residue. Single peptides that
      had different elution positions between samples from the native and peroxynitrite
      inactivated Mn-SOD on reverse-phase high performance liquid chromatography were
      isolated after successive digestion of the samples by staphylococcal serine
      protease and lysylendopeptidase and subjected to amino acid sequence and
      molecular mass analyses. We found that tyrosine 34 of the enzyme was exclusively
      nitrated to 3-nitrotyrosine by peroxynitrite. This residue is located near
      manganese and in a substrate O-2 gateway in Mn-SOD.

PMID- 9603907
TI  - Gain-of-function Chinese hamster ovary mutants LEC18 and LEC14 each express a
      novel N-acetylglucosaminyltransferase activity.
AB  - LEC18 and LEC14 cells are gain-of-function glycosylation mutants isolated from
      Chinese hamster ovary cells for resistance to pea lectin. Structural studies have
      shown that LEC18 cells synthesize complex N-glycans with a GlcNAc residue linked
      at the O-6 position of the core GlcNAc (Raju, T. S., Ray, M. K., and Stanley, P.
      (1995) J. Biol. Chem. 270, 30294-30302), whereas LEC14 cells synthesize complex N
      glycans with a GlcNAc residue linked at the O-2 position of the core beta-linked
      Man residue (Raju, T. S., and Stanley, P. (1996) J. Biol. Chem. 271, 7484-7493).
      Both modifications are novel and have not been reported in glycoproteins from any
      other source. We now show that, in both LEC18 and LEC14 cells, GlcNAc transfer is
      mediated by a distinct N-acetylglucosaminyltransferase (GlcNAc-T) activity. The
      LEC18 activity, termed GlcNAc-TVIII, transfers GlcNAc to GlcNAcbeta1-O-pNP and to
      a GlcNAc-terminating, biantennary, complex N-glycan, with or without a core
      fucose. By contrast, the LEC14 transferase, termed GlcNAc-TVII, does not have
      significant activity with simple acceptors, and transfers GlcNAc preferentially
      to a GlcNAc-terminating biantennary glycopeptide that contains a core fucose
      residue. The acceptor specificities and other biochemical properties of GlcNAc
      TVII and GlcNAc-TVIII differ from previously characterized GlcNAc-transferases
      including GlcNAc-TIII, indicating that they represent new members of the
      mammalian GlcNAc-T group of transferases.

PMID- 9603908
TI  - Cot kinase activates tumor necrosis factor-alpha gene expression in a cyclosporin
      A-resistant manner.
AB  - Cot kinase is a protein serine/threonine kinase, classified as a mitogen
      activated protein kinase kinase kinase, implicated in T lymphocyte activation.
      Here we show that an increase in Cot kinase expression promotes tumor necrosis
      factor-alpha (TNF-alpha) production in Jurkat T cells stimulated by soluble anti
      CD3 or by low concentrations of phorbol 12,13-dibutyrate (PDBu) and calcium
      ionophore. Overexpression of Cot kinase in Jurkat cells activates TNF-alpha gene
      expression. Cot kinase promotes TNF-alpha promoter activation to a similar extent
      as calcium ionophore and PDBu or soluble anti-CD28 and PDBu. Neither phorbol
      esters nor calcium ionophore can replace Cot kinase on TNF-alpha promoter-driven
      transcription. Expression of a dominant negative form of Cot kinase inhibits TNF
      alpha promoter activation induced by stimulation with either calcium ionophore
      and PDBu, soluble anti-CD28 and PDBu, or soluble anti-CD3 and PDBu. TNF-alpha
      promoter-driven transcription by Cot kinase is partially mediated by MAPK/ERK
      kinase and is cyclosporin A-resistant. Cot kinase increases at least the AP-1 and
      AP-2 response elements. These data indicate that Cot kinase plays a critical role
      in TNF-alpha production.

PMID- 9603909
TI  - A new class of phosphotransferases phosphorylated on an aspartate residue in an
      amino-terminal DXDX(T/V) motif.
AB  - When incubated with their substrates, human phosphomannomutase and L-3
      phosphoserine phosphatase are known to form phosphoenzymes with chemical
      characteristics of an acyl-phosphate. The phosphorylated residue in
      phosphomannomutase has now been identified by mass spectrometry after reduction
      of the phosphoenzyme with tritiated borohydride and trypsin digestion. It is the
      first aspartate in a conserved DVDGT motif. Replacement of either aspartate of
      this motif by asparagine or glutamate resulted in complete inactivation of the
      enzyme. The same mutations performed in the DXDST motif of L-3-phosphoserine
      phosphatase also resulted in complete inactivation of the enzyme, except for the
      replacement of the second aspartate by glutamate, which reduced the activity by
      only about 40%. This suggests that the first aspartate of the motif is also the
      phosphorylated residue in L-3-phosphoserine phosphatase. Data banks contained
      seven other phosphomutases or phosphatases sharing a similar, totally conserved
      DXDX(T/V) motif at their amino terminus. One of these (beta-phosphoglucomutase)
      is shown to form a phosphoenzyme with the characteristics of an acyl-phosphate.
      In conclusion, phosphomannomutase and L-3-phosphoserine phosphatase belong to a
      new phosphotransferase family with an amino-terminal DXDX(T/V) motif that serves
      as an intermediate phosphoryl acceptor.

PMID- 9603910
TI  - Direct inhibition of the pancreatic beta-cell ATP-regulated potassium channel by
      alpha-ketoisocaproate.
AB  - The ATP-regulated potassium (KATP) channel plays an essential role in the control
      of insulin release from the pancreatic beta-cell. In the present study we have
      used the patch-clamp technique to study the direct effects of alpha
      ketoisocaproate on the KATP channel in isolated patches and intact pancreatic
      beta-cells. In excised inside-out patches, the activity of the KATP channel was
      dose-dependently inhibited by alpha-ketoisocaproate, half-maximal concentration
      being approximately 8 mM. The blocking effect of alpha-ketoisocaproate was fully
      reversible. Stimulation of channel activity by the addition of ATP/ADP (ratio 1)
      did not counteract the inhibitory effect of alpha-ketoisocaproate. In the
      presence of the metabolic inhibitor sodium azide, alpha-ketoisocaproate was still
      able to inhibit single channel activity in excised patches and to block whole
      cell KATP currents in intact cells. No effect of alpha-ketoisocaproate could be
      obtained on either the large or the small conductance Ca2+-regulated K+ channel.
      Enzymatic treatment of the patches with trypsin prevented the inhibitory effect
      of alpha-ketoisocaproate. Based on these observations, it is unlikely that the
      blocking effect of alpha-ketoisocaproate is due to an unspecific effect on K+
      channel pores. Leucine, the precursor of alpha-ketoisocaproate, did not affect
      KATP channel activity in excised patches. Our findings are compatible with the
      view that alpha-ketoisocaproate not only affects the beta-cell stimulus secretion
      coupling by generation of ATP but also by direct inhibition of the KATP channel.

PMID- 9603911
TI  - Molecular mechanisms of promoter regulation of the gp34 gene that is trans
      activated by an oncoprotein Tax of human T cell leukemia virus type I.
AB  - We investigated the molecular mechanism of transcriptional activation of the gp34
      gene by the Tax oncoprotein of human T cell leukemia virus type I (HTLV-I). gp34
      is a type II transmembrane molecule belonging to the tumor necrosis factor family
      and is constitutively expressed on HTLV-I-producing cells but not normal resting
      T cells. The transcriptional regulatory region of the gp34 gene was activated by
      HTLV-I Tax in the human T cell line Jurkat, in which endogenous gp34 is induced
      by Tax. Sequence analysis demonstrated that two NF-kappaB-like elements (1 and 2)
      were present in the regulatory region. Both NF-kappaB-like elements were able to
      bind to NF-kappaB or its related factor(s) in a Tax-dependent manner.
      Chloramphenicol acetyltransferase assays indicated that NF-kappaB-like element 1
      was Tax-responsive, although the activity was lower than that the native
      promoter. NF-kappaB-like element 2 elevated promoter activity when combined with
      NF-kappaB-like element 1, indicating cooperative function of the elements for
      maximum promoter function. Unlike typical NF-kappaB elements, the NF-kappaB-like
      elements in gp34 were not activated by treatment of Jurkat cells with phorbol
      ester despite induction of the NF-kappaB-like binding activity. Chloramphenicol
      acetyltransferase reporter assays using the region upstream of the NF-kappaB-like
      elements identified an upstream region that reduced transcription from cognate
      and noncognate core promoters in a Tax-independent manner. Our results imply
      complex regulation of expression of the gp34 gene and suggest implication of gp34
      in proliferation of HTLV-I infected T cells.

PMID- 9603912
TI  - Requirements for the adaptor protein role of dihydrolipoyl acetyltransferase in
      the up-regulated function of the pyruvate dehydrogenase kinase and pyruvate
      dehydrogenase phosphatase.
AB  - The dihydrolipoyl acetyltransferase (E2 component) is a 60-mer assembled via its
      COOH-terminal domain with exterior E1-binding domain and two lipoyl domains (L2
      then L1) sequentially connected by mobile linker regions. E2 facilitates markedly
      enhanced function of the pyruvate dehydrogenase kinase (PDK) and pyruvate
      dehydrogenase phosphatase (PDP). Human E2 structures were prepared with only one
      lipoyl domain (L1 or L2) or with alanines substituted at the sites of lipoylation
      (Lys-46 in L1 or Lys-173 in L2). The L2 domain and its lipoyl group were shown to
      be essential for markedly enhanced PDP function and were required for greatly up
      regulated PDK function. The complete absence of the L1 domain reduced the
      enhancements of both of these activities but not the maximal effector-stimulated
      PDK activity through acetylation of L2. With nonlipoylated L2 present, lipoylated
      L1 supported a lesser enhancement in PDK function with significant stimulation
      upon acetylation of L1. Prevention of L1 lipoylation in K46AE2 removed this
      competitive L1 role and enhanced L2-facilitated PDK activity beyond that of
      native E2 when PDK activity was measured in the absence or in the presence of
      stimulatory effectors. Thus, the E2-L2 domain has a paramount role in
      facilitating enhanced PDK and PDP function but inclusion of E2-L1 domain, even in
      a noninteracting (nonlipoylated) form, contributes to the marked elevation of
      these activities.

PMID- 9603913
TI  - Inhibition by platelet-activating factor of Src- and hepatocyte growth factor
      dependent invasiveness of intestinal and kidney epithelial cells.
      Phosphatidylinositol 3'-kinase is a critical mediator of tumor invasion.
AB  - This study was designed to characterize platelet-activating factor receptor (PAF
      R) expression and function in normal and cancerous human colonic epithelial
      cells. PAF-R gene transcripts were analyzed by reverse transcription-polymerase
      chain reaction and Southern blot, using three sets of primers corresponding
      either to the coding region of the human PAF-R sequence (polymerase chain
      reaction product: 682 base pairs (bp)) or to the leukocyte- and tissue-type
      transcripts of 166 and 252 bp, respectively. An elongated splice variant was
      identified in the 5'-untranslated region of the tissue-type PAF-R transcript (334
      bp) in colonic epithelial crypts and tumors. In human colonic PCmsrc cells
      transformed by c-src oncogene, the hepatocyte growth factor (HGF)-dependent
      invasiveness of collagen gels was abolished by 0.1 microM PAF and restored by the
      PAF-R antagonists WEB2086 and SR27417. PAF blocked HGF-induced tyrosine
      phosphorylation of p125 focal adhesion kinase. The phosphatidylinositol 3'-kinase
      (PI3'-K) inhibitors wortmannin and LY294002 totally blocked the HGF-induced
      invasion. Similar effects were observed in ts-srcMDCK kidney epithelial cells
      transformed by a v-Src temperature-sensitive mutant: (i) PAF and wortmannin
      exerted additive inhibitory effects on Src-induced invasion and (ii) activated
      and dominant negative forms of p110alpha PI3'-K, respectively, amplified and
      abrogated the Src- and HGF-dependent invasiveness of parental and ts-srcMDCK
      cells. We also provided the first evidence for the contribution of rapamycin
      insensitive, pertussis toxin-dependent G-protein pathways to the integration of
      the signals emerging from activated Met and PAF receptors. These results indicate
      that PI3'-K is a critical transducer of invasiveness and strongly suggest that
      PAF exerts a negative control on invasion by inhibiting this signaling pathway. A
      possible beneficial role of PAF analogs on tumor invasion is therefore proposed.

PMID- 9603914
TI  - Minor modifications of a cholecystokinin-B/gastrin receptor non-peptide
      antagonist confer a broad spectrum of functional properties.
AB  - The development of non-peptide agonists for peptide hormone receptors would
      markedly expand the treatment options for a large number of diseases. However,
      difficulty in identifying non-peptide molecules which possess intrinsic activity
      has been a major obstacle in achieving this goal. At present, most of the known
      non-peptide ligands for peptide hormone receptors appear in standard functional
      assays to be antagonists. Here, we report that a constitutively active mutant of
      the human cholecystokinin-B/gastrin receptor, Leu325 --> Glu, offers the
      potential to detect even trace agonist activity of ligands which, at the wild
      type receptor isoform, appear to lack efficacy. The enhanced functional
      sensitivity of the mutant receptor enabled us to detect intrinsic activity of L
      365,260, an established non-peptide antagonist for the cholecystokinin-B/gastrin
      receptor. Extending from this observation, we were able to demonstrate that minor
      structural modifications could convert L-365, 260 into either: (i) an agonist or
      (ii) an inverse agonist (attenuates ligand-independent signaling). The ability to
      confer functional activity to small non-peptide ligands suggests that the
      properties of endogenous peptide hormones can be mimicked, and even extended, by
      considerably less complex molecules.

PMID- 9603915
TI  - Calnexin associates with monomeric and oligomeric (disulfide-linked) CD3delta
      proteins in murine T lymphocytes.
AB  - The antigen-binding receptor expressed on most T lymphocytes consists of
      disulfide-linked clonotypic alphabeta heterodimers noncovalently associated with
      monomeric CD3gamma,delta,epsilon proteins and disulfide-linked zeta zeta
      homodimers, collectively referred to as the T cell antigen receptor (TCR)
      complex. Here, we examined and compared the disulfide linkage status of newly
      synthesized TCR proteins in murine CD4(+)CD8(+) thymocytes and splenic T cells.
      These studies demonstrate that CD3delta proteins exist as both monomeric and
      oligomeric (disulfide-linked) species that differentially assemble with
      CD3epsilon subunits in CD4(+)CD8(+) thymocytes and splenic T cells.
      Interestingly, unlike previous results on glucose trimming and TCR assembly of
      CD3delta proteins in splenic T cells (Van Leeuwen, J. E. M., and K. P. Kearse
      (1996) J. Biol. Chem. 271, 9660-9665), we found that glucose residues were not
      invariably removed from CD3delta glycoproteins prior to their assembly with
      CD3epsilon subunits in CD4(+)CD8(+) thymocytes. Finally, these studies show that
      calnexin associates with both monomeric and disulfide-linked CD3delta proteins in
      murine T cells. The data in the current report demonstrate that CD3delta proteins
      exist as both monomeric and disulfide-linked molecules in murine T cells that
      differentially associate with partner TCR chains in CD4(+)CD8(+) thymocytes and
      splenic T cells. These results are consistent with the concept that folding and
      assembly of CD3delta proteins is a function of their oxidation state.

PMID- 9603916
TI  - The INS 5' variable number of tandem repeats is associated with IGF2 expression
      in humans.
AB  - The minisatellite DNA polymorphism consisting of a variable number of tandem
      repeats (VNTR) at the human INS (insulin gene) 5'-flanking region has
      demonstrated allelic effects on insulin gene transcription in vitro and has been
      associated with the level of insulin gene expression in vivo. We now show that
      this VNTR also has effects on the nearby insulin-like growth factor II gene
      (IGF2) in human placenta in vivo and in the HepG2 hepatoma cell line in vitro. We
      show that higher steady-state IGF2 mRNA levels are associated with shorter
      alleles (class I) than the longer class III alleles in term placentae. In vitro,
      reporter gene activity was greater from reporter gene constructs with IGF2
      promoter 3 in the presence of class I alleles than from those with class III.
      Taken together with the documented transcriptional effects on the insulin gene,
      we propose that the VNTR may act as a long range control element affecting the
      expression of both INS and IGF2. The localization of a type 1 diabetes
      susceptibility locus (IDDM2) to the VNTR itself suggests that either or both of
      these genes may be involved in the biologic effects of IDDM2.

PMID- 9603917
TI  - Novel subunit composition of a renal epithelial KATP channel.
AB  - Unique ATP-inhibitable K+ channels (KATP) in the kidney determine the rate of
      urinary K+ excretion and play an essential role in extracellular K+ balance.
      Here, we demonstrate that functionally similar low sulfonylurea affinity KATP
      channels are formed by two heterologous molecules, products of Kir1.1a and cystic
      fibrosis transmembrane conductance regulator (CFTR) genes. Co-injection of CFTR
      and Kir1.1a cRNA into Xenopus oocytes lead to the expression of K+ selective
      channels that retained the high open probability behavior of Kir1.1a but acquired
      sulfonylurea sensitivity and ATP-dependent gating properties. Similar to the KATP
      channels in the kidney but different from KATP channels in excitable tissues, the
      Kir1.1a/CFTR channel was inhibited by glibenclamide with micromolar affinity.
      Since the expression of Kir1.1a and CFTR overlap at sites in the kidney where the
      low sulfonylurea affinity KATP are expressed, our study offers evidence that
      these native KATP channels are comprised of Kir1.1a and CFTR. The implication
      that Kir subunits can interact with ABC proteins beyond the subfamily of
      sulfonylurea receptors provides an intriguing explanation for functional
      diversity in KATP channels.

PMID- 9603918
TI  - Pressure-induced dissociation of carbamoyl-phosphate synthetase domains. The
      catalytically active form is dimeric.
AB  - Carbamoyl-phosphate synthetase consists of an amidotransferase domain or subunit
      (GLN) that hydrolyzes glutamine and transfers the ammonia to the synthetase
      component (CPS) where the biosynthetic reaction occurs. The CPS domain is
      composed of two homologous subdomains, CPS.A and CPS.B, that catalyze different
      ATP-dependent reactions involved in carbamoyl phosphate synthesis. When the
      individual CPS.A and CPS.B subdomains were individually cloned and expressed in
      Escherichia coli (Guy, H. I., and Evans, D. R. (1996) J. Biol. Chem. 271, 13762
      13769), they were found to be functionally equivalent and could each
      independently catalyze carbamoyl phosphate synthesis. The proposal was advanced
      that, although the monomers could catalyze the individual partial reactions,
      overall synthesis of carbamoyl phosphate required a homodimer of CPS.A or CPS.B.
      To test this hypothesis, the GLN-CPS.B dimer was reversibly dissociated at 1500
      bar in a high pressure cell. Dissociation was accompanied by a loss of both
      glutamine- and ammonia-dependent CPSase activity. Activity was recovered once the
      protein was returned to atmospheric pressure. If the sample was cross-linked
      before exposure to high pressure, there was no dissociation and no loss of
      biosynthetic activity. In contrast, the bicarbonate-dependent ATPase and the
      carbamoyl phosphate-dependent ATP synthetase activities were largely unaffected
      by pressure-induced dissociation. These experiments confirmed the hypothesis that
      the synthesis of carbamoyl phosphate requires the concerted action of the two
      active sites within the homodimer.

PMID- 9603919
TI  - Role of beta112 Cys (G14) in homo- (beta4) and hetero- (alpha2 beta2) tetramer
      hemoglobin formation.
AB  - In order to assess the role of beta112 Cys in homo- and hetero-tetrameric
      hemoglobin formation, we expressed four beta112 variants (beta112Cys-->Asp,
      beta112Cys-->Ser, beta112Cys-->Thr, and beta112Cys-->Val) and studied assembly
      with alpha chains in vitro. beta112 Cys is normally present at beta1 beta2 and
      alpha1 beta1 interaction sites in homo- (beta4) and hetero-tetramers (alpha2
      beta2). beta4 formation in vitro was influenced by the amino acid at beta112.
      beta112 Asp completely inhibited formation of homo-tetramers, whereas beta112 Ser
      showed only slight inhibition. In contrast, beta112 Thr or Val enhanced homo
      tetramer formation compared with betaA chains. Association constants for homo
      tetramer formation increased in the order of beta112Cys-->Ser, betaA, beta112Cys-
      >Thr, and beta112Cys-->Val, whereas the value for beta112Cys-->Asp was zero under
      the same conditions. These beta112 changes also affected in vitro alpha2 beta2
      hetero-tetramer formation. Order of alpha2 beta2 formation under limiting alpha
      globin chain conditions showed Hb betaC112S > Hb A > Hb S = Hb betaC112T = Hb
      betaC112V >>> Hb betaC112D. Hb beta112D can form tetrameric hemoglobin, but this
      beta112 change promotes dissociation into alpha and beta chains instead of alpha
      beta dimer formation upon dilution. These results indicate that amino acids at
      alpha1 beta1 interaction sites such as beta112 on the G helix play a key role in
      stable alpha beta dimer formation. Our findings suggest, in addition to
      electrostatic interaction between alpha and beta chains, that dissociation of
      beta4 homo-tetramers to monomers and hydrophobic interactions of the beta112
      amino acid with alpha chains governs stable alpha1 beta1 interactions, which then
      results in formation of functional hemoglobin tetramers. Information gained from
      these studies should increase our understanding of the mechanism of assembly of
      multi-subunit proteins.

PMID- 9603920
TI  - Transcription from the thyroid hormone-dependent promoter of the Xenopus laevis
      thyroid hormone receptor betaA gene requires a novel upstream element and the
      initiator, but not a TATA Box.
AB  - The thyroid hormone receptor (TR) beta genes in Xenopus laevis are regulated by
      thyroid hormone in all organs of an animal during metamorphosis. This
      autoregulation appears to be critical for systematic transformations of different
      organs as a tadpole is transformed into a frog. To understand this
      autoregulation, we have previously identified a thyroid hormone response element
      in the hormone-dependent promoter of the X. laevis TRbetaA gene. We report here
      the detailed characterization of the promoter. We have now mapped the
      transcription start site and demonstrated the existence of an initiator element
      at the start site critical for promoter function. More important, our deletion
      and mutational experiments revealed a novel upstream DNA element that is located
      125 base pairs upstream of the start site and that is essential for active
      transcription from the promoter. Promoter reconstitution experiments showed that
      this novel element does not function as an enhancer, but acts as a core promoter
      element, which, together with the initiator, directs accurate transcription from
      the promoter. Finally, we provide evidence for the existence of a protein(s) that
      specifically recognizes this element. Our studies thus demonstrate that the
      TRbetaA promoter has a unique organization consisting of an initiator and a novel
      upstream promoter element. Such an organization may be important for the
      ubiquitous but tissue-dependent temporal regulation of the gene by thyroid
      hormone during amphibian metamorphosis.

PMID- 9603922
TI  - A soluble major histocompatibility complex class I peptide-binding platform
      undergoes a conformational change in response to peptide epitopes.
AB  - Class I major histocompatibility complexes (MHC) are heterotrimeric structures
      comprising heavy chains (HC), beta2-microglobulin (beta2-m), and short antigenic
      peptides of 8-10 amino acids. These components assemble in the endoplasmic
      reticulum and are released to the cell surface only when a peptide of the
      appropriate length and sequence is incorporated into the structure. The binding
      of beta2-m and peptide to HC is cooperative, and there is indirect evidence that
      the formation of a stable heterotrimer from an unstable HC:beta2-m heterodimer
      involves a peptide-induced conformational change in the HC. Such a conformational
      change could ensure both a strong interaction between the three components and
      also signal the release of stably assembled class I MHC molecules from the
      endoplasmic reticulum. A peptide-induced conformational change in HC has been
      demonstrated in cell lysates lacking beta2-m to which synthetic peptides were
      added. Many features of this conformational change suggest that it may be
      physiologically relevant. In an attempt to study the peptide-induced
      conformational change in detail we have expressed a soluble, truncated form of
      the mouse H-2Db HC that contains only the peptide binding domains of the class I
      molecule. We have shown that this peptide-binding "platform" is relatively stable
      in physiological buffers and undergoes a conformational change that is detectable
      with antibodies, in response to synthetic peptides. We also show that the
      structural features of peptides that induce this conformational change in the
      platform are the same as those required to observe the conformational change in
      full-length HC. In this respect, therefore, the HC alpha1 and alpha2 domains,
      which together form the peptide binding site of class I MHC, are able to act
      independently of the rest of the molecule.

PMID- 9603921
TI  - Free ricin A chain, proricin, and native toxin have different cellular fates when
      expressed in tobacco protoplasts.
AB  - The catalytic A subunit of ricin can inactivate eukaryotic ribosomes, including
      those of Ricinus communis where the toxin is naturally produced. How such plant
      cells avoid intoxication has remained an open question. Here we report the
      transient expression of a number of ricin A chain-encoding cDNA constructs in
      tobacco protoplasts. Ricin A chain entered the endoplasmic reticulum lumen, where
      it was efficiently glycosylated, but it was toxic to the cells and disappeared
      with time in a brefeldin A-insensitive manner, suggesting reverse translocation
      to the cytosol and eventual degradation. Proricin (the natural precursor form
      containing A and B chains joined together by a linker sequence) was glycosylated,
      transported to the vacuole, and processed to its mature form, but was not toxic.
      Free ricin A chain and proricin were not secreted, whereas free ricin B chain was
      found entirely in the extracellular medium. The coexpression of ricin A and B
      chains resulted in the formation of disulfide-linked, transport-competent
      heterodimers, which were secreted, with a concomitant reduction in the observed
      cytotoxicity. These results suggest that the production of ricin as a precursor
      is essential for its routing to the vacuole and for protection of ricin-producing
      cells.

PMID- 9603923
TI  - The C-terminal domain of matrilin-2 assembles into a three-stranded alpha-helical
      coiled coil.
AB  - Matrilin-2 is a member of von Willebrand factor A containing extracellular matrix
      proteins in which the cDNA-derived sequence shows similar domain organization to
      cartilage matrix protein/matrilin-1, but information on the protein structure is
      limited. Here we studied the oligomerization potential of a synthetic peptide NH2
      ENLILFQNVANEEVRKLTQRLEEMTQRMEALENRLKYR-COOH corresponding to the C-terminal
      sequence of mouse matrilin-2. The central portion of this sequence shows a
      periodicity of hydrophobic residues occupying positions a and d of a heptad
      pattern (abcdefg)n, which is characteristic for alpha-helical coiled-coil
      proteins. Circular dichroism spectroscopy revealed a high alpha-helical content,
      and the shape of the spectra is indicative for a coiled-coil conformation.
      Chemical cross-linking and size exclusion chromatography suggest a homotrimeric
      configuration. Thermal denaturation in benign buffer shows a single cooperative
      transition with DeltaH0 = -375 kJ/mol. Melting temperatures Tm varied from 38 to
      51 degreesC within a concentration range of 10 to 85 microM, which is about 35
      degreesC lower than determined for a peptide corresponding to the C-terminal
      domain of matrilin-1. The data suggest that despite the low sequence identity
      within this region, matrilin-2 will form a homotrimer as matrilin-1 does.

PMID- 9603924
TI  - Human xenomitochondrial cybrids. Cellular models of mitochondrial complex I
      deficiency.
AB  - The subunits forming the mitochondrial oxidative phosphorylation system are coded
      by both nuclear and mitochondrial genes. Recently, we attempted to introduce
      mtDNA from non-human apes into a human cell line lacking mtDNA (rho degrees), and
      succeeded in producing human-common chimpanzee, human-pigmy chimpanzee, and human
      gorilla xenomitochondrial cybrids (HXC). Here, we present a comprehensive
      characterization of oxidative phosphorylation function in these cells.
      Mitochondrial complexes II, III, IV, and V had activities indistinguishable from
      parental human or non-human primate cells. In contrast, a complex I deficiency
      was observed in all HXC. Kinetic studies of complex I using decylubiquinone or
      NADH as limiting substrates showed that the Vmax was decreased in HXC by
      approximately 40%, and the Km for the NADH was significantly increased (3-fold, p
      < 0.001). Rotenone inhibition studies of intact cell respiration and pyruvate
      malate oxidation in permeabilized cells showed that 3 nM rotenone produced a mild
      effect in control cells (0-10% inhibition) but produced a marked inhibition of
      HXC respiration (50-75%). Immunoblotting analyses of three subunits of complex I
      (ND1, 75 and 49 kDa) showed that their relative amounts were not significantly
      altered in HXC cells. These results establish HXC as cellular models of complex I
      deficiency in humans and underscore the importance of nuclear and mitochondrial
      genomes co-evolution in optimizing oxidative phosphorylation function.

PMID- 9603925
TI  - T cell activation through the CD43 molecule leads to Vav tyrosine phosphorylation
      and mitogen-activated protein kinase pathway activation.
AB  - CD43, the most abundant membrane protein of T lymphocytes, is able to initiate
      signals that lead to Ca2+ mobilization and interleukin-2 production, yet the
      molecular events involved in signal transduction pathway of the CD43 molecule are
      only beginning to be understood. We have shown recently that cross-linking CD43
      on the cell surface of human T lymphocytes with the anti-CD43 monoclonal antibody
      L10 leads to CD43-Fyn kinase interactions and to Fyn phosphorylation on tyrosine
      residues. This interaction seems to be mediated by the SH3 domain of Fyn and a
      proline-rich sequence located in the cytoplasmic domain of CD43. Here we show
      that CD43-specific activation of human T lymphocytes induced tyrosine
      phosphorylation of the adaptor protein Shc and of the guanine exchange factor
      Vav, as well as the formation of a macromolecular complex that comprises Shc,
      GRB2, and Vav. CD43 ligation resulted in enhanced formation of Vav.SLP-76
      complexes and in the activation and nuclear translocation of ERK2. Cross-linking
      of the CD43 molecule in 3T3-CD43(+) cells induced luciferase activity from a
      construct under the control of the Fos serum responsive element. Altogether,
      these data suggest that the mitogen-activated protein kinase pathway is involved
      in CD43-dependent interleukin-2 gene expression.

PMID- 9603926
TI  - Integrins regulate the association and phosphorylation of paxillin by c-Abl.
AB  - The c-Abl proto-oncogene is a non-receptor tyrosine kinase whose activity and
      localization are regulated by integrins. Cell adhesion to fibronectin triggers
      the transient recruitment of c-Abl from the nucleus to focal adhesions and
      activation of its tyrosine kinase. To investigate the integrin regulation of c
      Abl, proteins that interact with c-Abl following cell adhesion were assayed.
      Several proteins that were phosphorylated on tyrosine were found to transiently
      co-precipitate with c-Abl during cell adhesion, and one was identified as the
      focal adhesion protein paxillin. Abl also became transiently phosphorylated in
      response to cell adhesion. In addition, paxillin was found to serve as substrate
      for the adhesion-activated c-Abl kinase. These results suggest that c-Abl may
      mediate effects of integrins on cell functions by phosphorylating paxillin.

PMID- 9603927
TI  - Cysteine scanning of the surroundings of an alkali-ion binding site of the
      glutamate transporter GLT-1 reveals a conformationally sensitive residue.
AB  - Glutamate transporters remove this transmitter from the extracellular space by
      cotransport with three sodium ions and a proton. The cycle is completed by
      translocation of a potassium ion in the opposite direction. Recently we have
      identified two adjacent amino acid residues of the glutamate transporter GLT-1
      that influence potassium coupling. Using the scanning cysteine accessibility
      method we have now explored the highly conserved region surrounding them.
      Replacement of each of the five consecutive residues 396-400 by cysteine
      abolished transport activity but at several other positions the substitution is
      tolerated. One residue, tyrosine 403, was identified where cysteine substitution
      renders the transporter sensitive to modification by positively charged
      methanethiosulfonate derivates in a sodium-protectable fashion. In the presence
      of sodium, the nontransported glutamate analogue dihydrokainate potentiated the
      covalent modification, presumably by binding to the glutamate site and locking
      the protein in a conformation in which tyrosine 403 is accessible from the
      external bulk medium. In contrast, transported substrates significantly slowed
      the reaction, suggesting that during the transport cycle residue 403 becomes
      occluded. On the other hand, transportable substrates are not able to protect
      Y403C transporters against N-ethylmaleimide, which is highly permeant but unable
      to modify cysteine residues buried within membrane proteins. These results
      indicate that tyrosine 403 is alternately accessible from either side of the
      membrane, consistent with its role as structural determinant of the potassium
      binding site.

PMID- 9603928
TI  - Phospholamban domain Ib mutations influence functional interactions with the Ca2+
      ATPase isoform of cardiac sarcoplasmic reticulum.
AB  - Alanine-scanning mutagenesis of amino acids 21-30, forming cytoplasmic domain Ib
      in phospholamban (PLN), revealed that mutation to Ala of Asn27, Gln29, and Asn30
      results in gain of inhibitory function. In an earlier study (Kimura, Y.,
      Kurzydlowski, K., Tada, M. , and MacLennan, D. H. (1997) J. Biol. Chem. 272,
      15061-15064), gain of function in PLN transmembrane domain II mutants was
      correlated with pentamer destabilization, leading to proposals that the PLN
      monomer is the active inhibitory species, that dissociation of the PLN pentamer
      is one determinant of PLN inhibitory function and that dissociation of the
      PLN.cardiac sarco(endo)plasmic Ca2+-ATPase isoform (SERCA2a) complex is a second
      determinant. Because each of the new domain Ib mutants contained a normal ratio
      of pentamer to monomer in SDS-polyacrylamide gel electrophoresis, gain of
      function must have resulted from mechanisms other than destabilization of
      pentameric structure. Evidence that domain Ib and domain II mutants act through
      different sites and different mechanisms was provided by a monomeric double
      mutant, N30A/I40A, in which the enhanced inhibitory function of each single
      mutant was additive. Evidence for an alteration in stability of the PLN/SERCA2a
      heterodimer was obtained in a study of double mutant N27A/N34A in which
      inhibitory function was regained by combining a gain of function, domain Ib
      mutation with a loss of function domain II mutation. These results support the
      proposal that PLN inhibition of SERCA2a involves, first, depolymerization of PLN
      and, second, the formation of inhibitory interactions between monomeric PLN and
      SERCA2a.

PMID- 9603929
TI  - Recognition sites of 3'-OH group by T7 RNA polymerase and its application to
      transcriptional sequencing.
AB  - When analyzing the elongation mechanisms in T7 RNA polymerase (T7 RNAP)by using
      site-directed mutagenesis and a protein expression system, we identified the
      recognition sites of the rNTP 3'-OH group in T7 RNAP. On the basis of three
      dimensional crystal structure analysis, we selected and analyzed six candidate
      sites interacting with the 3'-OH group of rNTP in T7 RNAP. We found that the Phe
      644 and Phe-667 sites are responsible for the high selectivity of T7 RNAP for
      rNTPs. Also, we constructed the protein mutations of these residues, F644Y and
      F667Y, which display a >200-fold higher affinity than the wild type for 3'-dNTPs.
      These findings indicate that the phenylalanine residues of 644 and 667
      specifically interact with the 3'-OH group. Thus, these mutants, F644Y and F667Y,
      with incorporation of 3'-dNTP terminators, which is similar to native rNTPs, can
      offer low backgrounds and equal intensities of the sequencing ladders in our
      method, called "transcriptional sequencing. "

PMID- 9603930
TI  - A kinetic analysis of the oligonucleotide-modulated ATPase activity of the
      helicase domain of the NS3 protein from hepatitis C virus. The first cycle of
      interaction of ATP with the enzyme is unique.
AB  - Hepatitis C virus (HCV) helicase (E) formed spectrofluorometrically detectable
      complexes with a 16-mer and HF16 (a 16-mer with 5'-hexachlorofluoresceinyl
      moiety). The interaction of helicase with these effectors was investigated by
      kinetic techniques to determine if the complexes were kinetically competent for
      ATP hydrolysis. kcat values with the 16-mer and HF16 were 2.7 and 36 s-1,
      respectively. The maximal value of the rate constant for the approach of an
      intermediate to the steady-state level has to be at least 4-fold greater than
      kcat for it to be kinetically competent. This value was 1.2 s-1 with HF16 and
      "E.ATP" and was 1.82 s-1 with ATP and E.HF16. These values were too small for
      formation of these intermediates to be kinetically competent in ATP hydrolysis.
      Dissociation of "E.HF16. ATP" (0.34 s-1) was also too slow to contribute
      significantly to catalysis. Furthermore, the Km of E.HF16 for ATP (3 mircoM) was
      significantly less than the Km for ATP hydrolysis at a saturating concentration
      of HF16 (320 microM). HCV helicase has two nucleotide-binding sites per monomer.
      If the fluorescence changes observed were associated with structure changes
      preceding steady-state catalysis (isomerization), pre-steady-state data could be
      reconciled with the turnover data. Data for the 16-mer yielded similar
      conclusions.

PMID- 9603931
TI  - Redox properties of tryptophan tryptophylquinone enzymes. Correlation with
      structure and reactivity.
AB  - The pH dependence of the redox potentials for the oxidized/reduced couples of
      methylamine dehydrogenase (MADH) and aromatic amine dehydrogenase (AADH) were
      determined. For each enzyme, a change of -30 mV/pH unit was observed, indicating
      that the two-electron transfer is linked to the transfer of a single proton. This
      result differs from what was obtained from redox studies of a tryptophan
      tryptophylquinone (TTQ) model compound for which the two-electron couple is
      linked to the transfer of two protons. This result also distinguishes the redox
      properties of the enzyme-bound TTQ from those of the membrane-bound quinone
      components of respiratory and photosynthetic electron transfer chains that
      transfer two protons per two electrons. This difference is attributed to the
      accessibility of TTQ to solvent in the enzymes. One of the quinol hydroxyls is
      shielded from solvent and thus is not protonated. The unusual property of TTQ
      enzymes of stabilizing the anionic form of the reduced quinol is important for
      the reaction mechanism of MADH because it allows stabilization of physiologically
      important reaction intermediates. Examination of the extent to which
      disproportionation of the MADH and AADH semiquinones occurred as a function of pH
      revealed that the equilibrium concentration of semiquinone increased with pH.
      This indicates that the proton transfer is linked to the semiquinone/quinol
      couple. Therefore, the quinol is singly protonated, and the semiquinone is
      unprotonated and anionic. It was also shown that the oxidation-reduction midpoint
      potential for AADH is 20 mV less positive than that of MADH over the range of pH
      values that was studied and that the TTQ semiquinone of AADH was less stable than
      that of MADH. This may be explained by differences in the active site
      environments of the two enzymes, which modulate their respective redox
      properties.

PMID- 9603932
TI  - Cyclic nucleotide regulation of type-1 plasminogen activator-inhibitor mRNA
      stability in rat hepatoma cells. Identification of cis-acting sequences.
AB  - Type-1 plasminogen activator-inhibitor (PAI-1) is a major physiologic inhibitor
      of plasminogen activation. Incubation of HTC rat hepatoma cells with the cyclic
      nucleotide analogue, 8-bromo-cAMP, causes a dramatic increase in tissue-type
      plasminogen activator activity secondary to a 90% decrease in PAI-1 mRNA.
      Although 8-bromo-cAMP causes a modest decrease in PAI-1 transcription, regulation
      is primarily the result of a 3-fold increase in the rate of PAI-1 mRNA
      degradation. To determine the cis-acting sequences required for cyclic nucleotide
      regulation, we have stably transfected HTC cells with chimeric genes containing
      sequences from the rat PAI-1 cDNA and the mouse beta-globin gene and examined the
      effect of cyclic nucleotides on the decay rate of these transcripts. The mRNA
      transcribed from the beta-globin gene is stable and not cyclic nucleotide
      regulated, whereas the transcript from a construct containing the beta-globin
      coding region and the PAI-1 3'-untranslated region (UTR) is destabilized in the
      presence of 8-bromo-cAMP, suggesting that this response is mediated by sequences
      in the PAI-1 3'-UTR. Analyses by deletion of sequences from this chimeric
      construct indicate that, whereas more than one region of the PAI-1 3'-UTR can
      confer cyclic nucleotide responsiveness, the 3'-most 134-nucleotide sequence
      alone is sufficient to do so. Insertion of PAI-1 sequences within the beta-globin
      3'-UTR confirms that the 3'-most 134 nucleotides of PAI-1 mRNA can confer cyclic
      nucleotide regulation of stability on a heterologous transcript, suggesting that
      this sequence may play a major role in hormonal regulation of PAI-1 mRNA
      stability.

PMID- 9603933
TI  - The phosphate carrier from yeast mitochondria. Dimerization is a prerequisite for
      function.
AB  - Wild type phosphate carrier (PIC) from Saccharomyces cerevisiae and recombinant
      PIC proteins with different C-terminal extensions were expressed in Escherichia
      coli as inclusion bodies. From these, PIC was isolated with the detergent sodium
      lauroyl sarcosinate in a form, partially monomeric and unfolded. This PIC
      associates to stable dimers after exchanging the detergent to the polyoxyethylene
      detergent C12E8 and dialysis. Combining two differently tagged monomers of PIC
      and following this with affinity chromatography yields defined homo- and
      heterodimeric forms of PIC, which are all fully active after reconstitution. As a
      member of the mitochondrial carrier family PIC is supposed to function as a
      homodimer. We investigated its dimeric nature in the functionally active state
      after reconstitution. When reconstituting PIC monomers a sigmoidal dependence of
      transport activity on the amount of inserted protein is observed, whereas
      insertion of PIC dimers leads to a linear dependence. Heterodimeric PIC
      constructs consisting of both an active and an inactivated subunit do not
      catalyze phosphate transport. In contrast, reconstitution of a mixture of active
      and inactive monomeric subunits led to partially active carrier. These
      experiments prove (i) that PIC does not function in monomeric form, (ii) that PIC
      dimers are stable both in the solubilized state and after membrane insertion, and
      (iii) that transport catalyzed by PIC dimers involves functional cross-talk
      between the two monomers.

PMID- 9603934
TI  - Photoinactivation of fluorescein isothiocyanate-modified Na,K-ATPase by 2'(3')-O
      (2,4,6-trinitrophenyl)8-azidoadenosine 5'-diphosphate. Abolition of E1 and E2
      partial reactions by sequential block of high and low affinity nucleotide sites.
AB  - The Na,K-ATPase activity of the sodium pump exhibits apparent multisite kinetics
      toward ATP, a feature that is inherent to the minimal enzyme unit, the alpha beta
      protomer. We have argued that this should arise from separate catalytic and
      noncatalytic sites on the alpha beta protomer as fluorescein isothiocyanate
      (FITC) blocks a high affinity ATP site on all alpha subunits and yet the modified
      Na, K-ATPase retains a low affinity response to nucleotides (Ward, D. G., and
      Cavieres, J. D. (1996) J. Biol. Chem. 271, 12317-12321). We now find that 2'(3')
      O-(2,4,6-trinitrophenyl)8-azido-adenosine 5'-diphosphate (TNP-8N3-ADP), a high
      affinity photoactivatable analogue of ATP, can inhibit the K+-phosphatase
      activity of the FITC-modified enzyme during assays in dimmed light. The
      inhibition occurs with a Ki of 140 microM at 20 mM K+; it requires the adenine
      ring as 2'(3')-O-(2,4 6-trinitrophenyl) (TNP)-UDP or TNP-uridine are less potent
      and 2,4,6-trinitrobenzene-sulfonate is ineffective. Under irradiation with UV
      light, TNP-8N3-ADP inactivates the K+-phosphatase activity of the fluorescein
      enzyme and also its phosphorylation by [32P]Pi. The photoinactivation process is
      stimulated by Na+ or Mg2+, and is inhibited by K+ or excess TNP-ADP. In the
      presence of 50 mM Na+ and 1 mM Mg2+, TNP-8N3-ADP photoinactivates with a K0.5 of
      15 microM. Furthermore, TNP-8N3-ADP photoinactivates the FITC-modified,
      solubilized alpha beta protomers, even more effectively than the membrane-bound
      fluorescein-enzyme. These results strongly suggest that catalytic and allosteric
      ATP sites coexist on the alpha beta protomer of Na,K-ATPase.

PMID- 9603935
TI  - Myocyte enhancer factor 2 (MEF2)-binding site is required for GLUT4 gene
      expression in transgenic mice. Regulation of MEF2 DNA binding activity in insulin
      deficient diabetes.
AB  - We have previously demonstrated that important regulatory elements responsible
      for regulated expression of the human GLUT4 promoter are located between -1154
      and -412 relative to transcription initiation (Olson, A. L., and Pessin, J. E.
      (1995) J. Biol. Chem. 270, 23491-23495). Through further analysis of this
      promoter regulatory region, we have identified a perfectly conserved myocyte
      enhancer factor 2 (MEF2)-binding domain (-CTAAAAATAG-) that is necessary, but not
      sufficient, to support tissue-specific expression of a chloramphenicol
      acetyltransferase reporter gene in transgenic mice. Biochemical analysis of this
      DNA element demonstrated the formation of a specific DNA-protein complex using
      nuclear extracts isolated from heart, hindquarter skeletal muscle, and adipose
      tissue but not from liver. DNA binding studies indicated that this element
      functionally interacted with the MEF2A and/or MEF2C MADS family of DNA binding
      transcription factors. MEF2 DNA binding activity was substantially reduced in
      nuclear extracts isolated from both heart and skeletal muscle of diabetic mice,
      which correlated with decreased transcription rate of the GLUT4 gene. MEF2
      binding activity completely recovered to control levels following insulin
      treatment. Together these data demonstrated that MEF2 binding activity is
      necessary for regulation of the GLUT4 gene promoter in muscle and adipose tissue.

PMID- 9603936
TI  - Transcription factor IIA derepresses TATA-binding protein (TBP)-associated factor
      inhibition of TBP-DNA binding.
AB  - The interaction of the general transcription factor (TF) IIA with TFIID is
      required for transcription activation in vitro. TFIID consists of the TATA
      binding protein (TBP) and TBP associated factors (TAFIIs). TFIIA binds directly
      to TBP and stabilizes its interaction with TATA-containing DNA. In this work, we
      present evidence that TAFIIs inhibit TBP-DNA and TBP-TFIIA binding, and that
      TFIIA stimulates transcription, in part, by overcoming this TAFII-mediated
      inhibition of TBP-DNA binding. TFIIA mutants modestly compromised for interaction
      with TBP were found to be significantly more defective in forming complexes with
      TFIID. Subtle changes in the stability or conformation of the TFIIA-TBP complex
      resulted in a failure of TFIIA to overcome TAFII-mediated inhibition of TBP-DNA
      binding and transcription function. Inhibition of TBP-DNA binding by TAFIIs could
      be partially relieved by limited proteolysis of TFIID. Proteolysis significantly
      stimulated TFIIA-TFIID-TATA binding in both electrophoresis mobility shift assay
      and DNase I footprinting but had little effect on complexes formed with TBP.
      Recombinant TAFII250 inhibits TBP-DNA binding, whereas preincubation of TFIIA
      with TBP prevents this inhibition. Thus, TFIIA competes with TAFII250 for access
      to TBP and alters the TATA binding properties of the resulting complex.
      Transcriptional activation by Zta was enhanced by temperature shift inactivation
      of TAFII250 in the ts13 cell line, suggesting that TAFII250 has transcriptional
      inhibitory activity in vivo. Together, these results suggest that TAFIIs may
      regulate transcription initiation by inhibiting TBP-TFIIA and TBP-DNA complex
      formation.

PMID- 9603937
TI  - Identification of a new Pyk2 isoform implicated in chemokine and antigen receptor
      signaling.
AB  - Pyk2 is a protein tyrosine kinase that links G-protein-coupled receptors,
      inflammatory cytokines, and extracellular stimuli that elevate intracellular
      calcium concentration with activation of the mitogen-activated protein kinase
      pathways and regulation of ion channel functions. Here we describe the
      identification, cloning, and characterization of a new isoform of Pyk2 (Pyk2-H)
      that is generated by alternative RNA splicing. Pyk2-H is mainly expressed in
      hematopoietic cells including T-cells, B-cells, and natural killer cells.
      Engagement of T-cell or B-cell antigen receptors leads to rapid tyrosine
      phosphorylation of Pyk2-H. Pyk2-H is also activated in response to the chemokines
      RANTES and macrophage inflammatory protein-1beta in T cells. In addition, we show
      that glutathione S-transferase fusion proteins containing the carboxyl termini of
      Pyk2 and Pyk2-H bind to a different set of tyrosine-phosphorylated proteins in
      thymus lysates. Specific expression of Pyk2-H and its activation by antigens or
      chemokines in hematopoietic cells may contribute toward the generation of cell
      type-specific signals involved in host immune responses.

PMID- 9603938
TI  - RNA molecules that bind to and inhibit the active site of a tyrosine phosphatase.
AB  - Protein tyrosine phosphatases (PTPases) are essential proteins in many cellular
      processes. In vitro selection was used to evolve high affinity RNA aptamers to
      the Yersinia PTPase from two random pools varying in length. Selected aptamers
      from the two different pools share a 21-residue conserved sequence. They bind to
      their target with dissociation constants of 18 and 28 nM and inhibit the enzyme
      with IC50 values of 10 and 35 nM, but do not bind a related PTPase. Modification
      of the PTPase's active site cysteine with the alkylating agent iodoacetate
      results in a loss of binding affinity. These experiments suggest that the
      selected aptamers act by binding at or near the active site and might therefore
      be useful in defining the interactions between PTPases and their targets.

PMID- 9603939
TI  - Phosphorylation and inhibition of rat glucocorticoid receptor transcriptional
      activation by glycogen synthase kinase-3 (GSK-3). Species-specific differences
      between human and rat glucocorticoid receptor signaling as revealed through GSK-3
      phosphorylation.
AB  - Transcriptional activation by the glucocorticoid receptor (GR) is regulated by
      both glucocorticoid binding and phosphorylation. The rat GR N-terminal
      transcriptional regulatory domain contains four major phosphorylation sites:
      threonine 171 (Thr171), serine 224 (Ser224), serine 232 (Ser232), and serine 246
      (Ser246). We have previously demonstrated that Ser224 and Ser232 are
      phosphorylated by cyclin-dependent kinases, while Ser246 is phosphorylated by the
      c-Jun N-terminal kinase. We report here that the remaining GR phosphorylation
      site, Thr171, is a target for glycogen synthase kinase-3 (GSK-3) in vitro and in
      cultured mammalian cells. Increasing GSK-3 activity through its overexpression in
      cultured cells inhibits GR transcriptional enhancement, an effect dependent upon
      Thr171. Correspondingly, overexpression of a constitutively active form of the
      GSK-3 inhibitor, protein kinase B/Akt, increases GR transcriptional enhancement.
      Overexpression of GSK-3 had no effect on GR-mediated transcriptional repression
      of AP1-dependent gene expression. Importantly, transcriptional activation by the
      human GR (hGR), which contains an alanine (Ala150) at the position equivalent to
      Thr171 in rat GR, is not affected by GSK-3 overexpression. Introduction of a
      threonine residue at this position (A150T) establishes GSK-3-mediated inhibition
      of hGR transcriptional activation. These findings demonstrate species-specific
      differences in GR signaling, as revealed through GSK-3 phosphorylation, which
      suggests that GR function in rodents may not fully recapitulate receptor action
      in humans and that hGR is capable of adopting the GSK-3 signaling pathway through
      a somatic mutation.

PMID- 9603940
TI  - DNA ligase I selectively affects DNA synthesis by DNA polymerases delta and
      epsilon suggesting differential functions in DNA replication and repair.
AB  - The joining of single-stranded breaks in double-stranded DNA is an essential step
      in many important processes such as DNA replication, DNA repair, and genetic
      recombination. Several data implicate a role for DNA ligase I in DNA replication,
      probably coordinated by the action of other enzymes and proteins. Since both DNA
      polymerases delta and epsilon show multiple functions in different DNA
      transactions, we investigated the effect of DNA ligase I on various DNA synthesis
      events catalyzed by these two essential DNA polymerases. DNA ligase I inhibited
      replication factor C-independent DNA synthesis by polymerase delta. Our results
      suggest that the inhibition may be due to DNA ligase I interaction with
      proliferating cell nuclear antigen (PCNA) and not to a direct interaction with
      the DNA polymerase delta itself. Strand displacement activity by DNA polymerase
      delta was also affected by DNA ligase I. The DNA polymerase delta holoenzyme
      (composed of DNA polymerase delta, PCNA, and replication factor C) was inhibited
      in the same way as the DNA polymerase delta core, strengthening the hypothesis of
      a PCNA interaction. Contrary to DNA polymerase delta, DNA synthesis by DNA
      polymerase epsilon was stimulated by DNA ligase I in a PCNA-dependent manner. We
      conclude that DNA ligase I displays different influences on the two multipotent
      DNA polymerases delta and epsilon through PCNA. This might be of importance in
      the selective involvement in DNA transactions such as DNA replication and various
      mechanisms of DNA repair.

PMID- 9603941
TI  - Isolation and characterization of the Saccharomyces cerevisiae LPP1 gene encoding
      a Mg2+-independent phosphatidate phosphatase.
AB  - The DPP1-encoded diacylglycerol pyrophosphate (DGPP) phosphatase enzyme accounts
      for half of the Mg2+-independent phosphatidate (PA) phosphatase activity in
      Saccharomyces cerevisiae. The LPP1 (lipid phosphate phosphatase) gene encodes a
      protein that contains a novel phosphatase sequence motif found in DGPP
      phosphatase and in the mouse Mg2+-independent PA phosphatase. A genomic copy of
      the S. cerevisiae LPP1 gene was isolated and was used to construct lpp1Delta and
      lpp1Delta dpp1Delta mutants. A multicopy plasmid containing the LPP1 gene
      directed a 12.9-fold overexpression of Mg2+-independent PA phosphatase activity
      in the S. cerevisiae lpp1Delta dpp1Delta double mutant. The heterologous
      expression of the S. cerevisiae LPP1 gene in Sf-9 insect cells resulted in a 715
      fold overexpression of Mg2+-independent PA phosphatase activity relative to
      control insect cells. The Mg2+-independent PA phosphatase activity encoded by the
      LPP1 gene was associated with the membrane fraction of the cell. The LPP1 gene
      product also exhibited lyso-PA phosphatase and DGPP phosphatase activities. The
      order of substrate preference was PA > lyso-PA > DGPP. Like the dpp1Delta mutant,
      the lpp1Delta mutant and the lpp1Delta dpp1Delta double mutant were viable and
      did not exhibit obvious growth defects. Biochemical analyses of lpp1Delta,
      dpp1Delta, and lpp1Delta dpp1Delta mutants showed that the LPP1 and DPP1 gene
      products encoded nearly all of the Mg2+-independent PA phosphatase and lyso-PA
      phosphatase activities and all of the DGPP phosphatase activity in S. cerevisiae.
      Moreover, the analyses of the mutants showed that the LPP1 and DPP1 gene products
      played a role in the regulation of phospholipid metabolism and the cellular
      levels of phosphatidylinositol and PA.

PMID- 9603942
TI  - Chromogranin A induces a neurotoxic phenotype in brain microglial cells.
AB  - Chromogranin A (CGA) belongs to a multifunctional protein family widely
      distributed in secretory vesicles in neurons and neuroendocrine cells. Within the
      brain, CGA is localized in neurodegenerative areas associated with reactive
      microglia. By using cultured rodent microglia, we recently described that CGA
      induces an activated phenotype and the generation of nitric oxide. These findings
      led us to examine whether CGA might affect neuronal survival, expression of
      neurofilaments, and high affinity gamma-aminobutyric acid uptake in neurons
      cultured in the presence or absence of microglial cells. We found that CGA was
      unable to exert a direct toxic effect on neurons but provoked neuronal injury and
      degeneration in the presence of microglial cells. These effects were observed
      with natural and recombinant CGA and with a recombinant N-terminal fragment
      corresponding to residues 1-78. CGA stimulated microglial cells to secrete heat
      stable diffusible neurotoxic agents. CGA also induced a marked accumulation of
      nitric oxide and tumor necrosis factor-alpha by microglia, but we could not
      establish a direct correlation between the levels of nitric oxide and tumor
      necrosis factor-alpha and the neuronal damage. The possibility that CGA
      represents an endogenous factor that triggers the microglial responses
      responsible for the pathogenesis of neuronal degeneration is discussed.

PMID- 9603943
TI  - Multiple proteins binding to a GATA-E box-GATA motif regulate the erythroid
      Kruppel-like factor (EKLF) gene.
AB  - Erythroid Kruppel-like factor (EKLF) is a zinc finger transcription factor
      required for beta-globin gene expression and is implicated as one of the key
      factors necessary for the fetal to adult switch in globin gene expression. In an
      effort to identify factors involved in the expression of this important erythroid
      specific regulatory protein, we have isolated the mouse EKLF gene and
      systematically analyzed the promoter region. Initially, a reporter construct with
      1150 base pairs of the EKLF 5'-region was introduced into transgenic mice and
      shown to direct erythroid-specific expression. We continued the expression
      studies in erythroid cells and have identified a sequence element consisting of
      two GATA sites flanking an E box motif. The three sites act in concert to elevate
      the transcriptional activity of the EKLF promoter. Each site is essential for
      EKLF expression indicating that the three binding sites do not work additively,
      but rather function as a unit. We further show that GATA-1 binds to the two GATA
      sites and present evidence for binding of another factor from erythroid cell
      nuclear extracts to the E box motif. These results are consistent with the
      formation of a quaternary complex composed of an E box dimer and two GATA-1
      proteins binding at a combined GATA-E box-GATA activator element in the distal
      EKLF promoter.

PMID- 9603944
TI  - Analysis of the structural requirements for lysosomal membrane targeting using
      transferrin receptor chimeras.
AB  - The sorting of membrane proteins to the lysosome requires tyrosine- or dileucine
      based targeting signals. Recycling receptors have similar signals, yet these
      proteins seldom enter the latter stages of the endocytic pathway. To determine
      how lysosomal and internalization signals differ, we prepared chimeric molecules
      consisting of the cytoplasmic tails of CD3 gamma-chain, lysosomal acid
      phosphatase, and lysosomal-associated membrane glycoprotein-1, each fused to the
      transmembrane and extracellular domains of the transferrin receptor (TR). Each
      chimera was expressed on the cell surface and rapidly internalized. Metabolic
      pulse-chase experiments showed that the CD3 gamma-chain and lysosomal acid
      phosphatase chimeras, unlike the lysosomal-associated membrane glycoprotein
      chimera, were rapidly degraded in a post-Golgi compartment following normal
      glycosylation. Transplantation of signals from CD3 gamma-chain and lysosomal acid
      phosphatase into the TR cytoplasmic tail in place of the native signal, Y20TRF23,
      indicated that each signal was sufficient to promote endocytosis but not
      lysosomal targeting of the resulting mutant. Transplantation of two CD3 signals
      at specific sites in the TR cytoplasmic tail or a single tyrosine-based signal in
      a truncated TR tail, however, was sufficient to promote lysosomal targeting. Our
      results therefore suggest that the relative position of the signal within the
      cytoplasmic tail is a critical feature that distinguishes lysosomal targeting
      signals from internalization signals.

PMID- 9603945
TI  - Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL.
AB  - TRAIL is a tumor necrosis factor-related ligand that induces apoptosis upon
      binding to its death domain-containing receptors, DR4 and DR5. Two additional
      TRAIL receptors, TRID/DcR1 and DcR2, lack functional death domains and function
      as decoy receptors for TRAIL. We have identified a fifth TRAIL receptor, namely
      osteoprotegerin (OPG), a secreted tumor necrosis factor receptor homologue that
      inhibits osteoclastogenesis and increases bone density in vivo. OPG-Fc binds
      TRAIL with an affinity of 3.0 nM, which is slightly weaker than the interaction
      of TRID-Fc or DR5-Fc with TRAIL. OPG inhibits TRAIL-induced apoptosis of Jurkat
      cells. Conversely, TRAIL blocks the anti-osteoclastogenic activity of OPG. These
      data suggest potential cross-regulatory mechanisms by OPG and TRAIL.

PMID- 9603946
TI  - Purification and characterization of a novel ceramidase from Pseudomonas
      aeruginosa.
AB  - We report here a novel type of ceramidase of Pseudomonas aeruginosa AN17 isolated
      from the skin of a patient with atopic dermatitis. The enzyme was purified 83,400
      fold with an overall yield of 21.1% from a culture supernatant of strain AN17.
      After being stained with a silver staining solution, the purified enzyme showed a
      single protein band, and its molecular mass was estimated to be 70 kDa on SDS
      polyacrylamide gel electrophoresis. The enzyme showed quite wide specificity for
      various ceramides, i.e. it hydrolyzed ceramides containing C12:0-C18:0 fatty
      acids and 7-nitrobenz-2-oxa-1, 3-diazole-labeled dodecanoic acid, and not only
      ceramide containing sphingosine (d18:1) or sphinganine (d18:0) but also
      phytosphingosine (t18:0) as the long-chain base. However, the enzyme did not
      hydrolyze galactosylceramide, sulfatide, GM1, or sphingomyelin, and thus was
      clearly distinguished from a Pseudomonas sphingolipid ceramide N-deacylase (Ito,
      M., Kurita, T., and Kita, K. (1995) J. Biol. Chem. 270, 24370-24374). This
      bacterial ceramidase had a pH optimum of 8.0-9.0, an apparent Km of 139 microM,
      and a Vmax of 5.3 micromol/min/mg using N-palmitoylsphingosine as the substrate.
      The enzyme appears to require Ca2+ for expression of the activity. Interestingly,
      the 70-kDa protein catalyzed a reversible reaction in which the N-acyl linkage of
      ceramide was either cleaved or synthesized. Our study demonstrated that
      ceramidase is widely distributed from bacteria to mammals.

PMID- 9603947
TI  - Caenorhabditis elegans contains two distinct acid sphingomyelinases.
AB  - Mounting evidence supports a role for acid sphingomyelinase (ASM) in cellular
      stress signaling. Only murine and human sphingomyelinases have been defined at
      the molecular level. These enzymes are the products of a conserved gene and at
      the amino acid level share 82% identity. In this study, we show that the nematode
      Caenorhabditis elegans possesses two ASMs, termed ASM-1 and ASM-2 encoded by two
      distinct genes, but lacks detectable neutral sphingomyelinase activity. The C.
      elegans ASMs are about 30% identical with each other and with the human and
      murine enzymes. The conserved regions include a saposin-like domain, proline-rich
      domain, and a putative signal peptide. In addition, 16 cysteines distributed
      throughout the molecules, and selected glycosylation sites, are conserved. The
      expression of these genes in C. elegans is regulated during development. Asm-1 is
      preferentially expressed in the embryo, whereas asm-2 is predominantly expressed
      in postembryonic stages. When transfected as Flag-tagged proteins into COS-7
      cells, ASM-1 is found almost entirely in a secreted form whereas only 20% of ASM
      2 is secreted. Only the secreted forms display enzymatic activity. Furthermore,
      ASM-2 requires addition of Zn2+ to be fully active, whereas ASM-1 is active in
      the absence of cation. C. elegans is the first organism to display two ASMs. This
      finding suggests the existence of an ASM gene family.

PMID- 9603948
TI  - Met-195 of the cholecystokinin-A receptor interacts with the sulfated tyrosine of
      cholecystokinin and is crucial for receptor transition to high affinity state.
AB  - Sulfation of the tyrosine at the seventh position from the C terminus of
      cholecystokinin (CCK) is crucial for CCK binding to the CCK-A receptor. Using
      three-dimensional modeling, we identified methionine 195 of the CCK-A receptor as
      a putative amino acid in interaction with the aromatic ring of the sulfated
      tyrosine of CCK. We analyzed the role played by the two partners of this
      interaction. The exchange of Met-195 for a leucine caused a minor decrease (2. 8
      fold) on the affinity of the high affinity sites for sulfated CCK-9, a strong
      drop (73%) of their number, and a 30-fold decrease on the affinity of the low and
      very low affinity sites for sulfated CCK-9, with no change in their number. The
      mutation also caused a 54-fold decrease of the potency of the receptor to induce
      inositol phosphates production. The high affinity sites of the wild-type CCK-A
      receptor were highly selective (800-fold) toward sulfated versus nonsulfated CCK,
      whereas low and very low affinity sites were poorly selective (10- and 18-fold).
      In addition, the M195L mutant bound, and responded to, sulfated CCK analogues
      with decreased affinities and potencies, whereas it bound and responded to
      nonsulfated CCK identically to the wild-type receptor. Thus, Met-195 interacts
      with the aromatic ring of the sulfated tyrosine to correctly position the
      sulfated group of CCK in the binding site of the receptor. This interaction is
      essential for CCK-dependent transition of the CCK-A receptor to a high affinity
      state. Our data should represent an important step toward the identification of
      the residue(s) of the receptor in interaction with the sulfate moiety of CCK and
      the understanding of the molecular mechanisms that govern CCK-A receptor
      activation.

PMID- 9603949
TI  - Coagulation factor XIIIa undergoes a conformational change evoked by glutamine
      substrate. Studies on kinetics of inhibition and binding of XIIIA by a cross
      reacting antifibrinogen antibody.
AB  - Coagulation factor XIIIa, plasma transglutaminase (endo-gamma-glutamine:epsilon
      lysine transferase EC 2.3.2.13) catalyzes isopeptide bond formation between
      glutamine and lysine residues and rapidly cross-links fibrin clots. A monoclonal
      antibody (5A2) directed to a fibrinogen Aalpha-chain segment 529-539 was
      previously observed from analysis of end-stage plasma clots to block fibrin alpha
      chain cross-linking. This prompted the study of its effect on nonfibrinogen
      substrates, with the prospect that 5A2 was inhibiting XIIIa directly. It
      inhibited XIIIa-catalyzed incorporation of the amine donor substrate
      dansylcadaverine into the glutamine acceptor dimethylcasein in an uncompetitive
      manner with respect to dimethylcasein utilization and competitively with respect
      to dansylcadaverine. Uncompetitive inhibition was also observed with the
      synthetic glutamine substrate, LGPGQSKVIG. Theoretically, uncompetitive
      inhibition arises from preferential interaction of the inhibitor with the enzyme
      substrate complex but is also found to inhibit gamma-chain cross-linking. The
      conjunction of the uncompetitive and competitive modes of inhibition indicates in
      theory that this bireactant system involves an ordered reaction in which docking
      of the glutamine substrate precedes the amine exchange. The presence of substrate
      enhanced binding of 5A2 to XIIIa, an interaction deemed to occur through a C
      terminal segment of the XIIIa A-chain (643-658, GSDMTVTVQFTNPLKE), 55% of which
      comprises sequences occurring in the fibrinogen epitope Aalpha-(529-540)
      (GSESGIFTNTKE). Removal of the C-terminal domain from XIIIa abolishes the
      inhibitory effect of 5A2 on activity. Crystallographic studies on recombinant
      XIIIa place the segment 643-658 in the region of the groove through which
      glutamine substrates access the active site and have predicted that for
      catalysis, a conformational change may accompany glutamine-substrate binding. The
      uncompetitive inhibition and the substrate-dependent binding of 5A2 provide
      evidence for the conformational change.

PMID- 9603950
TI  - The eukaryotic UDP-N-acetylglucosamine pyrophosphorylases. Gene cloning, protein
      expression, and catalytic mechanism.
AB  - A search of the yeast data base for a protein homologous to Escherichia coli UDP
      N-acetylglucosamine pyrophosphorylase yielded UAP1 (UDP-N-acetylglucosamine
      pyrophosphorylase), the Saccharomyces cerevisiae gene for UDP-N-acetylglucosamine
      pyrophosphorylase. The Candida albicans and human homologs were also cloned by
      screening a C. albicans genomic library and a human testis cDNA library,
      respectively. Sequence analysis revealed that the human UAP1 cDNA was identical
      to previously reported AGX1. A null mutation of the S. cerevisiae UAP1 (ScUAP1)
      gene was lethal, and when expressed under the control of ScUAP1 promoter, both C.
      albicans and Homo sapiens UAP1 (CaUAP1 and HsUAP1) rescued the ScUAP1-deficient
      S. cerevisiae cells. All the recombinant ScUap1p, CaUap1p, and HsUap1p possessed
      UDP-N-acetylglucosamine pyrophosphorylase activities in vitro. The yeast Uap1p
      utilized N-acetylglucosamine-1-phosphate as the substrate, and together with
      Agm1p, it produced UDP-N-acetylglucosamine from N-acetylglucosamine-6-phosphate.
      These results demonstrate that the UAP1 genes indeed specify eukaryotic UDP
      GlcNAc pyrophosphorylase and that phosphomutase reaction precedes uridyltransfer.
      Sequence comparison with other UDP-sugar pyrophosphorylases revealed that amino
      acid residues, Gly112, Gly114, Thr115, Arg116, Pro122, and Lys123 of ScUap1p are
      highly conserved in UDP-sugar pyrophosphorylases reported to date. Among these
      amino acids, alanine substitution for Gly112, Arg116, or Lys123 severely
      diminished the activity, suggesting that Gly112, Arg116, or Lys123 are possible
      catalytic residues of the enzyme.

PMID- 9603951
TI  - Structure and expression of the orphan nuclear receptor SHP gene.
AB  - To determine the organization of the orphan nuclear receptor SHP gene (Seol, W.,
      Choi, H.-S., and Moore, D.D. (1996) Science 272, 1336-1339), genomic clones were
      isolated from human and mouse genomic libraries. The SHP gene was composed of two
      exons interrupted by a single intron spanning approximately 1.8 kilobases in
      human and 1.2 kilobases in mouse. Genomic Southern blot analysis and fluorescence
      in situ hybridization of human metaphase chromosomes indicated that the SHP gene
      is located at the human chromosome 1p36.1 subband. The 5'-flanking regions of
      human and mouse SHP genes were highly conserved, showing 77% homology in the
      region of approximately 600 nucleotides upstream from the transcription start
      site. Primer extension analysis was carried out to determine the transcription
      start site of human SHP to 32 nucleotides downstream of a potential TATA box. The
      human SHP gene was specifically expressed in fetal liver, fetal adrenal gland,
      adult spleen, and adult small intestine. As expected from this expression
      pattern, the activity of the mouse SHP promoter measured by transient
      transfection was significantly higher in the adrenal-derived Y1 cells than HeLa
      cells.

PMID- 9603952
TI  - Coordinate transcription and physical linkage of domains in surfactin synthetase
      are not essential for proper assembly and activity of the multienzyme complex.
AB  - Bacterial peptide synthetases have two common features that appear to be strictly
      conserved. 1) The enzyme subunits are co-regulated at both transcriptional and
      translational level. 2) The organization of the different enzymatic domains
      constituting the enzyme fulfills the "colinearity rule" according to which the
      order of the domains along the chromosome parallels their functional hierarchy.
      Considering the high degree of conservation of these features, one would expect
      that mutations such as transcription uncoupling and domain dissociations,
      deletions, duplications, and reshuffling would result in profound effects on the
      quality and quantity of synthesized peptides. To start testing this hypothesis,
      we designed two mutants. In one mutant, the operon structure of surfactin
      synthetase was destroyed, thus altering the concerted expression of the enzyme
      subunits. In the other mutant, the thioesterase domain naturally fused to the
      last amino acid binding domain of surfactin was physically dissociated and
      independently expressed. When the lipopeptides secreted by the mutant Bacillus
      subtilis strains were purified and characterized, they appeared to be expressed
      approximately at the same level of the wild type surfactin and to be identical to
      it, indicating that specific domain-domain interactions rather than coordinated
      transcription and translation play the major role in determining the correct
      assembly and activity of peptide synthetases.

PMID- 9603953
TI  - The functions of five distinct mammalian phospholipase A2S in regulating
      arachidonic acid release. Type IIa and type V secretory phospholipase A2S are
      functionally redundant and act in concert with cytosolic phospholipase A2.
AB  - We examined the relative contributions of five distinct mammalian phospholipase
      A2 (PLA2) enzymes (cytosolic PLA2 (cPLA2; type IV), secretory PLA2s (sPLA2s;
      types IIA, V, and IIC), and Ca2+-independent PLA2 (iPLA2; type VI)) to
      arachidonic acid (AA) metabolism by overexpressing them in human embryonic kidney
      293 fibroblasts and Chinese hamster ovary cells. Analyses using these
      transfectants revealed that cPLA2 was a prerequisite for both the calcium
      ionophore-stimulated immediate and the interleukin (IL)-1- and serum-induced
      delayed phases of AA release. Type IIA sPLA2 (sPLA2-IIA) mediated delayed AA
      release and, when expressed in larger amounts, also participated in immediate AA
      release. sPLA2-V, but not sPLA2-IIC, behaved in a manner similar to sPLA2-IIA.
      Both sPLA2s-IIA and -V, but not sPLA2-IIC, were heparin-binding PLA2s that
      exhibited significant affinity for cell-surface proteoglycans, and site-directed
      mutations in residues responsible for their membrane association or catalytic
      activity markedly reduced their ability to release AA from activated cells.
      Pharmacological studies using selective inhibitors as well as co-expression
      experiments supported the proposal that cPLA2 is crucial for these sPLA2s to act
      properly. The AA-releasing effects of these sPLA2s were independent of the
      expression of the M-type sPLA2 receptor. Both cPLA2, sPLA2s-IIA, and -V were able
      to supply AA to downstream cyclooxygenase-2 for IL-1-induced prostaglandin E2
      biosynthesis. iPLA2 increased the spontaneous release of fatty acids, and this
      was further augmented by serum but not by IL-1. Finally, iPLA2-derived AA was not
      metabolized to prostaglandin E2. These observations provide evidence for the
      functional cross-talk or segregation of distinct PLA2s in mammalian cells in
      regulating AA metabolism and phospholipid turnover.

PMID- 9603954
TI  - Rapamycin inhibition of the G1 to S transition is mediated by effects on cyclin
      D1 mRNA and protein stability.
AB  - The immunosuppressant rapamycin has been shown previously to inhibit the G1/S
      transition in several cell types by prolonging the G1 phase of the cell cycle.
      This process appears to be controlled, in part, by the rapamycin-sensitive FK506
      binding protein-rapamycin-associated protein-p70 S6 kinase (p70(S6k)) pathway and
      the cyclin-dependent kinases (Cdk). We now show that in serum-stimulated NIH 3T3
      cells, rapamycin treatment delays the accumulation of cyclin D1 mRNA during
      progression through G1. Rapamycin also appears to affect stability of the
      transcript. The combined transcriptional and post-transcriptional effects of the
      drug ultimately result in decreased levels of cyclin D1 protein. Moreover,
      degradation of newly synthesized cyclin D1 protein is accelerated by rapamycin, a
      process prevented by inclusion of the proteasome inhibitor, N-acetyl-Leu-Leu
      norleucinal. The overall effect of rapamycin on cyclin D1 leads, in turn, to
      impaired formation of active complexes with Cdk4, a process which triggers
      retargeting of the p27(Kip1) inhibitor to cyclin E/Cdk2. In view of this novel
      experimental evidence, we discuss a possible mechanism for the rapamycin-induced
      cell cycle arrest at the G1/S transition.

PMID- 9603955
TI  - Proteolytic enzymes from larvae of the fire ant, Solenopsis invicta. Isolation
      and characterization of four serine endopeptidases.
AB  - The imported red fire ant (Solenopsis invicta) is a problematic pest in the
      Southern United States. The stages of development for these ants are as follows:
      egg, 1st, 2nd, 3rd, and 4th instar larvae, prepupae, pupae, and adult. The 4th
      instar larvae plays an important role in the survival of the colony in that it is
      totally responsible for the digestion of solid foods and the source of nutrients
      for the queen and adult workers. In our studies we have been successful in
      purifying and characterizing four proteinases from the 4th instar larvae. Based
      on substrate specificity, they appear to represent two chymotrypsin-like and two
      elastase-like proteinases. These are referred to as Soli C1, Soli C2, Soli E1,
      and Soli E2, with molecular masses of 25, 28, 23, and 24 kDa, respectively, based
      on SDS-PAGE. All enzymes were inhibited by diisopropyl fluorophosphate, a general
      serine class inhibitor. Various synthetic substrates with either Phe or Val in
      the P1 position, were readily cleaved by Soli C1/C2 or E1/E2, respectively. Each
      enzyme has been characterized as to pH optimum, pH stability, isoelectrofocusing
      and susceptibility to inhibition by a broad range of natural and synthetic
      proteinase inhibitors. Such compounds may prove useful for the development of
      insecticides to control fire ant infestation.

PMID- 9603956
TI  - Domain mapping of human apurinic/apyrimidinic endonuclease. Structural and
      functional evidence for a disordered amino terminus and a tight globular carboxyl
      domain.
AB  - We recently described the pre-steady state enzymatic binding kinetics of
      apurinic/apyrimidinic endonuclease (AP endo). In this report we describe the
      domain structure of the enzyme in solution determined by mild protease digestion
      in the presence and absence of substrate, product, and an efficient competitive
      inhibitor (HDP). AP endo is a 35.5-kDa protein with a high degree of homology to
      its prokaryotic counterpart, exonuclease III (Exo III), except for the amino
      terminus, which is lacking in the prokaryotic enzyme. The entire conserved region
      plus an additional 20 residues unique to the eukaryotic enzyme was inaccessible
      to trypsin and V8 protease, indicating that it forms a tight globular structure.
      In contrast, the amino-terminal 35 residues were readily accessible to all the
      proteases investigated, leading us to conclude that they associate poorly with
      the rest of the structure and constitute a highly fluid region. When AP endo was
      boiled with SDS and cooled prior to the addition of V8 protease, several acidic
      residues within the globular domain became protease-accessible, indicating rapid
      renaturation except along the nuclease fold with restoration of globular
      conformation for the carboxyl two-thirds of the molecule. Of all the proteases
      tested, only chymotrypsin was able to cleave internal to the globular portion
      without prior denaturation. Although AP endo cleaved with chymotrypsin retained
      full enzymatic activity, the activity was lost when the digested peptides were
      recovered after denaturation by heat and/or boiling in SDS, precipitation, and
      renaturation or when fragments were recovered from an SDS gel and renatured.
      Thus, the protein is probably held together strongly by noncovalent interactions
      that maintain enzymatic function after protease nicking. The three major
      chymotrypsin cleavage sites, Tyr-144, Leu-179, and Leu-205, became strikingly
      less accessible to protease digestion in the presence of abasic site-containing
      DNA. Since the three residues form a spherical triangle on the surface of the
      molecule on one side of the nuclease fold, there must be multiple means by which
      DNA containing an abasic site associates with the enzyme. The most likely
      explanation is that substrate and product, both of which were present during
      proteolysis, bind differently to the enzyme. Finally, the two cysteine residues
      thought to be involved in the redox reaction of AP endo with Jun protein were
      entirely inaccessible to proteolysis even after prolonged exposure of AP endo to
      reducing agents. Consequently, if AP endo plays a role in the physiological
      function of Jun, it must undergo major conformational changes in the process.
      Alternatively, the two cysteines could maintain an appropriate conformation such
      that other residues participate directly in the redox activity.

PMID- 9603957
TI  - Porcine submaxillary mucin forms disulfide-linked multimers through its amino
      terminal D-domains.
AB  - COS-7 cells expressing 1,360 residues from the amino terminus of porcine
      submaxillary mucin were used to determine whether this region, containing the D1,
      D2, and D3 domains, is involved in forming mucin multimers. Analysis of the
      proteins immunoprecipitated from the medium of transfected cells by reducing SDS
      gel electrophoresis showed a single N-glycosylated protein with no indication of
      proteolytically processed forms. Without prior reduction, only two proteins,
      corresponding to monomeric and disulfide-linked trimeric species, were observed.
      The expressed protein devoid of N-linked oligosaccharides also formed trimers,
      but was secreted from cells in significantly less amounts than glycosylated
      trimers. Pulse-chase studies showed that the disulfide-linked trimers were
      assembled inside the cells no earlier than 30 min after protein synthesis
      commenced and after the intracellular precursors were N-glycosylated. Trimer
      formation was inhibited in cells treated with brefeldin A, monensin, chloroquine,
      or bafilomycin A1, although only brefeldin A prevented the secretion of the
      protein. These results suggest that trimerization takes place in compartments of
      the Golgi complex in which the vacuolar H+-ATPase maintains an acidic pH.
      Coexpression in the same cells of the amino-terminal region and the disulfide
      rich carboxyl-terminal domain of the mucin showed that these structures were not
      disulfide-linked with one another. Cells expressing a DNA construct encoding a
      fusion protein between the amino- and carboxyl-terminal regions of the mucin
      secreted disulfide-linked dimeric and high molecular weight multimeric species of
      the recombinant mucin. The presence of monensin in the medium was without effect
      on dimerization, but inhibited the formation of disulfide-linked multimers. These
      studies suggest that disulfide-linked dimers of mucin are subsequently assembled
      into disulfide-linked multimers by the amino-terminal regions. They also suggest
      that the porcine mucin forms branched disulfide-linked multimers. This ability of
      the amino-terminal region of mucin to aid in the assembly of multimers is
      consistent with its amino acid identities to the amino-terminal region of human
      von Willebrand factor, which also serves to form disulfide-linked multimers of
      this protein.

PMID- 9603958
TI  - Novel galactose-binding proteins in Annelida. Characterization of 29-kDa tandem
      repeat-type lectins from the earthworm Lumbricus terrestris.
AB  - Novel type lectins were found in the phylum Annelida, i.e. in the earthworm,
      tubifex, leech, and lugworm. The lectins (29-31 kDa) were extracted from the
      worms without the use of detergent and purified by affinity chromatography on
      asialofetuin-agarose. On the basis of the partial primary structures of the
      earthworm Lumbricus terrestris 29-kDa lectin (EW29), degenerate primers were
      synthesized for use in the reverse transcriptase-polymerase chain reaction. An
      amplified 155-base pair fragment was used to screen a cDNA library. Four types of
      full-length clones were obtained, all of which encoded 260 amino acids, but which
      were found to differ at 29 nucleotide positions. Since three of them resulted in
      non-silent substitutions, EW29 mRNA was considered to be a mixture of at least
      three distinct polynucleotides encoding the following proteins: Ala44-Gln197
      Ile213 (clone 5), Gly44-Gln197-Val213 (clone 7), and Ala44-His197-Ile213 (clones
      8 and 9; different at the nucleotide level, but encoding an identical
      polypeptide). Genomic polymerase chain reaction using DNA from a single worm
      revealed that the single worm already had four sets of cDNAs. The EW29 protein
      showed two features. First, the lectin was composed of two homologous domains
      (14,500 Da) showing 27% identity with each other. When each of the domains was
      separately expressed in Escherichia coli, the C-terminal domain was found to bind
      to asialofetuin-agarose as strongly as the whole protein, whereas the N-terminal
      domain did not bind and only retardation was observed. EW29 was found to exist as
      a monomer under non-denaturing conditions. It had significant hemagglutinating
      activity, which was inhibited by a wide range of galactose-containing
      saccharides. Second, EW29 contained multiple short conserved motifs, "Gly-X-X-X
      Gln-X-Trp." Similar motifs have been found in many carbohydrate-recognizing
      proteins from an extensive variety of organisms, e.g. plant lectin ricin B-chain
      and Clostridium botulinum 33-kDa hemagglutinin. Therefore, these carbohydrate
      recognition proteins appear to form a protein superfamily.

PMID- 9603959
TI  - Stimulation of the DNA-dependent protein kinase by poly(ADP-ribose) polymerase.
AB  - The DNA-dependent protein kinase (DNA-PK) is a heterotrimeric enzyme that binds
      to double-stranded DNA and is required for the rejoining of double-stranded DNA
      breaks in mammalian cells. It has been proposed that DNA-PK functions in this DNA
      repair pathway by binding to the ends of broken DNA molecules and phosphorylating
      proteins that bind to the damaged DNA ends. Another enzyme that binds to DNA
      strand breaks and may also function in the cellular response to DNA damage is the
      poly(ADP-ribose) polymerase (PARP). Here, we show that PARP can be phosphorylated
      by purified DNA-PK, and the catalytic subunit of DNA-PK is ADP-ribosylated by
      PARP. The protein kinase activity of DNA-PK can be stimulated by PARP in the
      presence of NAD+ in a reaction that is blocked by the PARP inhibitor 1, 5
      dihydroxyisoquinoline. The stimulation of DNA-PK by PARP-mediated protein ADP
      ribosylation occurs independent of the Ku70/80 complex. Taken together, these
      results show that PARP can modify the activity of DNA-PK in vitro and suggest
      that these enzymes may function coordinately in vivo in response to DNA damage.

PMID- 9603960
TI  - Role of tyrosine kinase activity of epidermal growth factor receptor in the
      lysophosphatidic acid-stimulated mitogen-activated protein kinase pathway.
AB  - Recent evidence indicates that the epidermal growth factor (EGF) receptor
      mediates a branch of lysophosphatidic acid (LPA)-induced signal transduction
      pathways that activate mitogen-activated protein (MAP) kinase. However, it is
      unclear whether the intrinsic tyrosine kinase activity of EGF receptor is
      involved. We previously showed that reactive oxygen species (ROS) were involved
      in the LPA-stimulated MAP kinase pathway. Here, we identify tyrosine
      phosphorylation of EGF receptor as an LPA signaling step that requires ROS. To
      evaluate the role of the tyrosine kinase activity of EGF receptor in the LPA
      stimulated MAP kinase pathway, we examined the effects of an EGF receptor
      specific tyrosine kinase inhibitor, PD158780. PD158780 potently inhibited the LPA
      stimulated MAP kinase kinase 1/2 (MKK1/2) activation and EGF receptor tyrosine
      phosphorylation in HeLa cells, while it had no detectable effect on c-Src kinase
      activity. PD158780 also inhibited LPA-induced MKK1/2 activation and DNA synthesis
      in NIH 3T3 cells. Furthermore, we compared LPA-stimulated MKK1/2 and MAP kinase
      activation, transcriptional activity of the c-fos promoter, and DNA synthesis in
      B82L cells, which lack endogenous EGF receptor, and B82L cells expressing kinase
      defective or wild-type human EGF receptor. Results obtained from analysis of
      these cell lines suggest that the EGF receptor tyrosine kinase contributes to the
      LPA-stimulated MAP kinase activation, c-fos transcription, and mitogenesis.

PMID- 9603961
TI  - Disulfide bonds in the extracellular calcium-polyvalent cation-sensing receptor
      correlate with dimer formation and its response to divalent cations in vitro.
AB  - Extracellular calcium/polyvalent cation-sensing receptors (CaR) couple to G
      proteins and contain highly conserved extracellular cysteine residues.
      Immunoblotting of proteins from rat kidney inner medullary collecting duct
      endosomes with CaR-specific antibodies reveals alterations in the apparent
      molecular mass of CaR depending on protein denaturation conditions. When
      denatured by SDS under nonreducing conditions, CaR migrates as a putative dimeric
      species of 240-310 kDa. This is twice the predicted molecular mass of the CaR
      monomer observed after SDS denaturation in the presence of sulfhydryl-reducing
      agents. In sucrose density gradients, Triton X-100-solubilized CaR sediments as a
      220-kDa complex, not explainable by binding of G proteins to CaR monomers.
      Treatment of Triton-soluble CaR with divalent (Ca2+, Mg2+) and trivalent (Gd3+)
      metal ion CaR agonists, but not monovalent ions (Na+), partially shifts the
      electrophoretic mobility of CaR under reducing conditions from a predominantly
      monomeric to this putative dimeric species on immunoblots in a manner similar to
      their rank order of functional potency for CaR activation (Gd3+ >> Ca2+ > Mg2+).
      This Ca2+ effect is blocked by pretreatment with N-ethylmaleimide. We conclude
      that disulfide bonds present in CaRs mediate formation of dimers that are
      preserved in Triton X-100 solution. In addition, CaR exposure to Ca2+ induces
      formation of additional disulfide bonds within the Triton-soluble CaR complex.

PMID- 9603962
TI  - Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a
      common effector mechanism.
AB  - The present study identifies the operation of a signal tranduction pathway in
      mammalian cells that provides a checkpoint control, linking amino acid
      sufficiency to the control of peptide chain initiation. Withdrawal of amino acids
      from the nutrient medium of CHO-IR cells results in a rapid deactivation of p70
      S6 kinase and dephosphorylation of eIF-4E BP1, which become unresponsive to all
      agonists. Readdition of the amino acid mixture quickly restores the
      phosphorylation and responsiveness of p70 and eIF-4E BP1 to insulin. Increasing
      the ambient amino acids to twice that usually employed increases basal p70
      activity to the maximal level otherwise attained in the presence of insulin and
      abrogates further stimulation by insulin. Withdrawal of most individual amino
      acids also inhibits p70, although with differing potency. Amino acid withdrawal
      from CHO-IR cells does not significantly alter insulin stimulation of tyrosine
      phosphorylation, phosphotyrosine-associated phosphatidylinositol 3-kinase
      activity, c-Akt/protein kinase B activity, or mitogen-activated protein kinase
      activity. The selective inhibition of p70 and eIF-4E BP1 phosphorylation by amino
      acid withdrawal resembles the response to rapamycin, which prevents p70
      reactivation by amino acids, indicating that mTOR is required for the response to
      amino acids. A p70 deletion mutant, p70Delta2-46/DeltaCT104, that is resistant to
      inhibition by rapamycin (but sensitive to wortmannin) is also resistant to
      inhibition by amino acid withdrawal, indicating that amino acid sufficiency and
      mTOR signal to p70 through a common effector, which could be mTOR itself, or an
      mTOR-controlled downstream element, such as a protein phosphatase.

PMID- 9603963
TI  - Differential expression and association of calcium channel alpha1B and beta
      subunits during rat brain ontogeny.
AB  - Calcium functions as an essential second messenger during neuronal development
      and synapse acquisition. Voltage-dependent calcium channels (VDCC), which are
      critical to these processes, are heteromultimeric complexes composed of alpha1,
      alpha2/delta, and beta subunits. beta subunits function to direct the VDCC
      complex to the plasma membrane as well as regulate its channel properties. The
      importance of beta to neuronal functioning was recently underscored by the
      identification of a truncated beta4 isoform in the epileptic mouse lethargic (lh)
      (Burgess, D. L., Jones, J. M., Meisler, M. H., and Noebels, J. L. (1997) Cell 88,
      385-392). The goal of our study was to investigate the role of individual beta
      isoforms (beta1b, beta2, beta3, and beta4) in the assembly of N-type VDCC during
      rat brain development. By using quantitative Western blot analysis with anti
      alpha1B-directed antibodies and [125I-Tyr22]omega-conotoxin GVIA (125I-CTX)
      radioligand binding assays, we observed that only a small fraction of the total
      alpha1B protein present in embryonic and early postnatal brain expressed high
      affinity 125I-CTX-binding sites. These results suggested that subsequent
      maturation of alpha1B or its assembly with auxiliary subunits was required to
      exhibit high affinity 125I-CTX binding. The temporal pattern of expression of
      beta subunits and their assembly with alpha1B indicated a developmental pattern
      of expression of beta isoforms: beta1b increased 3-fold from P0 to adult, beta4
      increased 10-fold, and both beta2 and beta3 expression remained unchanged. As the
      beta component of N-type VDCC changed during postnatal development, we were able
      to identify both immature and mature forms of N-type VDCC. At P2, the relative
      contribution of beta is beta1b > beta3 >> beta2, whereas at P14 and adult the
      distribution is beta3 > beta1b = beta4. Although we observed no beta4 associated
      with the alpha1B at P2, beta4 accounted for 14 and 25% of total alpha1B/beta
      subunit complexes in P14 and adult, respectively. Thus, of the beta isoforms
      analyzed, only the beta4 was assembled with the rat alpha1B to form N-type VDCC
      with a time course that paralleled its level of expression during rat brain
      development. These results suggest a role for the beta4 isoform in the assembly
      and maturation of the N-type VDCC.

PMID- 9603964
TI  - alpha-enolase, a novel strong plasmin(ogen) binding protein on the surface of
      pathogenic streptococci.
AB  - The plasmin(ogen) binding property of group A streptococci is incriminated in
      tissue invasion processes. We have characterized a novel 45-kDa protein
      displaying strong plasmin(ogen) binding activity from the streptococcal surface.
      Based on its biochemical properties, we confirmed the identity of this protein as
      alpha-enolase, a key glycolytic enzyme. Dose-dependent alpha-enolase activity,
      immune electron microscopy of whole streptococci using specific antibodies, and
      the opsonic nature of polyclonal and monoclonal antibodies concluded the presence
      of this protein on the streptococcal surface. We, henceforth, termed the 45-kDa
      protein, SEN (streptococcal surface enolase). SEN is found ubiquitously on the
      surface of most streptococcal groups and serotypes and showed significantly
      greater plasmin(ogen) binding affinity compared with previously reported
      streptococcal plasminogen binding proteins. Both the C-terminal lysine residue of
      SEN and a region N-terminal to it play a critical role in plasminogen binding.
      Results from competitive plasminogen binding inhibition assays and cross-linking
      studies with intact streptococci indicate that SEN contributes significantly to
      the overall streptococcal ability to bind plasmin(ogen). Our findings, showing
      both the protected protease activity of SEN-bound plasmin and SEN-specific immune
      responses, provide evidence for an important role of SEN in the disease process
      and post-streptococcal autoimmune diseases.

PMID- 9603965
TI  - Histone acetylation is required to maintain the unfolded nucleosome structure
      associated with transcribing DNA.
AB  - Nucleosomes associated with transcribing chromatin of mammalian cells have an
      unfolded structure in which the normally buried cysteinyl-thiol group of histone
      H3 is exposed. In this study we analyzed transcriptionally active/competent DNA
      enriched chromatin fractions from chicken mature and immature erythrocytes for
      the presence of thiol-reactive nucleosomes using organomercury-agarose column
      chromatography and hydroxylapatite dissociation chromatography of chromatin
      fractions labeled with [3H]iodoacetate. In mature and immature erythrocytes, the
      active DNA-enriched chromatin fractions are associated with histones that are
      rapidly highly acetylated and rapidly deacetylated. When histone deacetylation
      was prevented by incubating cells with histone deacetylase inhibitors, sodium
      butyrate or trichostatin A, thiol-reactive H3 of unfolded nucleosomes was
      detected in the soluble chromatin and nuclear skeleton-associated chromatin of
      immature, but not mature, erythrocytes. We did not find thiol-reactive
      nucleosomes in active DNA-enriched chromatin fractions of untreated immature
      erythrocytes that had low levels of highly acetylated histones H3 and H4 or in
      chromatin of immature cells incubated with inhibitors of transcription
      elongation. This study shows that transcription elongation is required to form,
      and histone acetylation is needed to maintain, the unfolded structure of
      transcribing nucleosomes.

PMID- 9603966
TI  - Mutating a region of HIV-1 reverse transcriptase implicated in tRNA(Lys-3)
      binding and the consequences for (-)-strand DNA synthesis.
AB  - Recently, tRNALys-3 was cross-linked via its anticodon loop to human
      immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) between residues
      230 and 357 (Mishima, Y., and Steitz, J. A. (1995) EMBO J. 14, 2679-2687).
      Scanning the surface of this region identified three basic amino acids Lys249,
      Arg307, and Lys311 flanking a small crevice on the p66 thumb subdomain outside
      the primer-template binding cleft. To assess an interaction of this region with
      the tRNA anticodon loop, these p66 residues were altered to Glu or Gln. p66
      subunits containing K249Q, K311Q, K311E, and a dual R307E/K311E mutation formed a
      stable dimer with wild type p51. All mutants showed reduced affinity for tRNALys
      3 and supported significantly less (-)-strand DNA synthesis from this primer than
      the parental heterodimer. In contrast, these variants efficiently synthesized HIV
      1 (-)-strand strong-stop DNA from oligonucleotide primers and had minimal effect
      on RNase H activity, retaining endonucleolytic and directed cleavage of an
      RNA/DNA hybrid. Structural features of binary RT.tRNALys-3 complexes were
      examined by in situ footprinting, via susceptibility to 1, 10-phenanthroline
      copper-mediated cleavage. Unlike wild type RT, mutants p66(K311Q)/p51 and
      p66(K311E)/p51 failed to protect the tRNA anticodon domain from chemical
      cleavage, indicating a significant structural alteration in the binary RT.tRNA
      complex. These results suggest a crevice in the p66 thumb subdomain of HIV-1 RT
      supports an interaction with the tRNALys-3 anticodon loop critical for efficient
      (-)-strand DNA synthesis.

PMID- 9603967
TI  - Analysis of the Gs/mitogen-activated protein kinase pathway in mutant S49 cells.
AB  - Heterotrimeric G protein-coupled receptors can activate the mitogen-activated
      protein kinase (MAPK) cascade. Recent studies using pharmacological inhibitors or
      dominant-negative mutants of signaling molecules have advanced our understanding
      of the pathways from G protein-coupled receptors to MAPK. However, molecular
      genetic analysis of these pathways is inadequate in mammalian cells. Here, using
      the well characterized Gsalpha- and protein kinase A-deficient S49 mouse lymphoma
      cells, we provide the molecular genetic evidence that Gsalpha is responsible for
      transducing the beta-adrenergic receptor signal to MAPK in a protein kinase A
      dependent pathway involving Rap1 and Raf (but not Ras) molecules.

PMID- 9603968
TI  - Muscarinic acetylcholine receptors activate expression of the EGR gene family of
      transcription factors.
AB  - In order to search for genes that are activated by muscarinic acetylcholine
      receptors (mAChRs), we used an mRNA differential display approach in HEK293 cells
      expressing m1AChR. The zinc-finger transcription factor genes Egr-1, Egr-2, and
      Egr-3 were identified. Northern blot analyses confirmed that mRNA levels of Egr
      1, Egr-2, and Egr-3 increased readily after m1AChR stimulation and that a maximum
      was attained within 50 min. At that time, Egr-4 mRNA was also detectable. Western
      blots and electromobility shift assays demonstrated synthesis of EGR-1 and EGR-3,
      as well as binding to DNA recognition sites in response to m1AChR activation.
      Activation of m1AChR increased transcription from EGR-dependent promoters,
      including the acetylcholinesterase gene promoter. Activity-dependent regulation
      of Egr-1 mRNA expression and EGR-1 protein synthesis was also observed in cells
      expressing m2, m3, or m4AChR subtypes. Increased EGR-1 synthesis was mimicked by
      phorbol myristate acetate, but not by forskolin, and receptor-stimulated EGR-1
      synthesis was partially inhibited by phorbol myristate acetate down-regulation.
      Together, our results demonstrate that muscarinic receptor signaling activates
      the EGR transcription factor family and that PKC may be involved in intracellular
      signaling. The data suggest that transcription of EGR-dependent target genes,
      including the AChE gene, can be under the control of extracellular and
      intracellular signals coupled to muscarinic receptors.

PMID- 9603969
TI  - Cholecystokinin decreases intestinal hexose absorption by a parallel reduction in
      SGLT1 abundance in the brush-border membrane.
AB  - The dual lumenaly and vascularly perfused small intestine was used to determine
      the mechanism by which cholecystokinin octapeptide (CCK-8) decreases the rate of
      glucose absorption. With CCK-8 in the vascular perfusate the rate of 3-O-methyl-D
      glucose absorption decreased, whereas the rate of D-fructose absorption was
      unaffected. The substrate pool size within the tissue during steady-state
      transport, in the presence and absence of CCK-8, was estimated by compartmental
      analysis of the 3-O-methyl-D-glucose washout into the vascular bed. When CCK-8
      was included in the vascular perfusate, the absorptive cell pool size decreased
      when compared with untreated tissue. Both the steady-state hexose absorption data
      and the washout studies indicated that the locus of action of CCK-8 was the SGLT1
      transporter located in the brush-border membrane. The SGLT1 protein abundance in
      isolated brush-border membranes, as quantified by Western blotting, showed a
      decrease that paralleled the decrease in the steady-state transport rate induced
      by CCK-8. These results indicate that CCK-8 diminishes the rate of intestinal
      hexose absorption by decreasing SGLT1 protein abundance in the brush-border
      membrane of the rat jejunum and therefore provides evidence for acute enteric
      hormonal regulation of the rate of glucose absorption across the small intestine.

PMID- 9603970
TI  - Sphingomyelin synthase, a potential regulator of intracellular levels of ceramide
      and diacylglycerol during SV40 transformation. Does sphingomyelin synthase
      account for the putative phosphatidylcholine-specific phospholipase C?
AB  - Sphingomyelin synthase (SMS), an enzyme involved in sphingomyelin (SM) and
      ceramide metabolism, can potentially regulate, in opposite directions, the levels
      of ceramide and diacylglycerol. In this study SMS activity was investigated in
      normal and SV40-transformed human lung fibroblasts (WI38). The addition of [3H]C2
      ceramide to cells resulted in a time-dependent formation of [3H]C2-SM. At 24 h
      after treatment, normal WI38 cells cleared 17% of [3H]C2-ceramide producing
      [3H]C2-SM, which accounted for 13% of total radioactivity. On the other hand,
      SV40-transformed cells cleared 45% of [3H]C2-ceramide and produced C2-SM, which
      accounted for 24% of total radioactivity. This enhanced production of C2-SM was
      also supported by an increase in the total SMS activity of cells (measured in
      vitro), such that SV40-transformed cells had SMS activity of 222 pmol/mg of
      protein/h, whereas wild type cells had 78 pmol/mg of protein/h of activity.
      Additional studies aimed at examining the SMS activity directed at ceramide
      produced in the plasma membrane. Treatment of cells with exogenous bacterial
      sphingomyelinase (SMase) for 25 min resulted in cleavage of 90-95% of total SM
      and the concomitant generation of ceramide. After bacterial SMase treatment, wild
      type WI38 cells cleared ceramide very slowly (19.2 pmol of ceramide/nmol of
      phosholipid Pi after 6 h of incubation) and hardly regenerated any SM. On the
      other hand, SV40-transformed cells cleared ceramide much faster (41.1 pmol/nmol
      of Pi after 6 h of incubation) and regenerated approximately 80% of the original
      SM. These results show that the enhanced SMS activity of transformed cells is
      particularly pronounced when ceramide is produced in the plasma membrane.
      Finally, several observations led us to consider the relationship of SMS to the
      "putative" phosphatidylcholine-specific phospholipase C (PC-PLC). We, therefore,
      tested the effects of D609, a purported PC-PLC-specific inhibitor on the activity
      of SMS. D609 inhibited SMS activity in vitro. In addition, cellular studies
      showed that SMS activity was dramatically inhibited by concentrations of D609
      used previously to study PC-PLC (10-50 microg/ml). These results suggest SMS as
      an important biochemical target for D609, and they raise the distinct possibility
      that many of the roles of PC-PLC, especially in cell transformation, may be
      attributable to SMS.

PMID- 9603971
TI  - Bidirectional regulation of p38 kinase and c-Jun N-terminal protein kinase by
      insulin-like growth factor-I.
AB  - We have previously shown that insulin-like growth factor I (IGF-I) activation of
      the IGF-I receptor rescues SH-SY5Y human neuroblastoma cells from high glucose
      mediated programmed cell death (PCD). In the current study, we further explored
      the potential points in the cell death cascade where IGF-I receptor activation
      may afford neuroprotection. As an initial step, we examined the effects of the
      PCD stimulus, high glucose, on stress-activated protein kinases, specifically the
      two mitogen-activated protein kinases p38 kinase and c-Jun N-terminal kinase
      (JNK). High glucose treatment activated the tyrosine phosphorylation of both p38
      kinase and JNK in a dose- and time-dependent fashion. We next examined the
      effects of IGF-I on JNK and p38 kinase under normoglycemic and hyperglycemic
      conditions. IGF-I activated p38 kinase alone and had additive effects on glucose
      induced p38 kinase phosphorylation. In contrast, IGF-I inhibited glucose
      activation of JNK phosphorylation and JNK activity. IGF-I also inhibited the
      glucose-induced nuclear translocation of JNK, but did not effect glucose-induced
      translocation of p38 kinase. Finally, IGF-I inhibition of JNK phosphorylation was
      blocked by the mitogen-activated protein kinase/extracellular signal-regulated
      kinase inhibitor, PD98059. Collectively, these data imply cross-talk between the
      mitogen-activated protein kinase pathway and JNK and suggest that IGF-I
      activation of mitogen-activated protein kinases interferes with JNK activation
      and protects cells from PCD.

PMID- 9603972
TI  - Calcium signaling by cyclic ADP-ribose, NAADP, and inositol trisphosphate are
      involved in distinct functions in ascidian oocytes.
AB  - ADP-ribosyl cyclase catalyzes the synthesis of two structurally and functionally
      different Ca2+ releasing molecules, cyclic ADP-ribose (cADPR) from beta-NAD and
      nicotinic acid-adenine dinucleotide phosphate (NAADP) from beta-NADP. Their Ca2+
      mobilizing effects in ascidian oocytes were characterized in connection with that
      induced by inositol 1,4,5-trisphosphate (InsP3). Fertilization of the oocyte is
      accompanied by a decrease in the oocyte Ca2+ current and an increase in membrane
      capacitance due to the addition of membrane to the cell surface. Both of these
      electrical changes could be induced by perfusion, through a patch pipette, of
      nanomolar concentrations of cADPR or its precursor, beta-NAD, into unfertilized
      oocytes. The changes induced by beta-NAD showed a distinctive delay consistent
      with its enzymatic conversion to cADPR. The cADPR-induced changes were inhibited
      by preloading the oocytes with a Ca2+ chelator, indicating the effects were due
      to Ca2+ release induced by cADPR. Consistently, ryanodine (at high concentration)
      or 8-amino-cADPR, a specific antagonist of cADPR, but not heparin, inhibited the
      cADPR-induced changes. Both inhibitors likewise blocked the membrane insertion
      that normally occurred at fertilization consistent with it being mediated by a
      ryanodine receptor. The effects of NAADP were different from those of cADPR.
      Although NAADP induced a similar decrease in the Ca2+ current, no membrane
      insertion occurred. Moreover, pretreatment of the oocytes with NAADP inhibited
      the post-fertilization Ca2+ oscillation while cADPR did not. A similar Ca2+
      oscillation could be artificially induced by perfusing into the oocytes a high
      concentration of InsP3 and NAADP could likewise inhibit such an InsP3-induced
      oscillation. This work shows that three independent Ca2+ signaling pathways are
      present in the oocytes and that each is involved in mediating distinct changes
      associated with fertilization. The results are consistent with a hierarchical
      organization of Ca2+ stores in the oocyte.

PMID- 9603973
TI  - Regulation of type II renal Na+-dependent inorganic phosphate transporters by
      1,25-dihydroxyvitamin D3. Identification of a vitamin D-responsive element in the
      human NAPi-3 gene.
AB  - Vitamin D is an important regulator of phosphate homeostasis. The effects of
      vitamin D on the expression of renal Na+-dependent inorganic phosphate (Pi)
      transporters (types I and II) were investigated. In vitamin D-deficient rats, the
      amounts of type II Na+-dependent Pi transporter (NaPi-2) protein and mRNA were
      decreased in the juxtamedullary kidney cortex, but not in the superficial cortex,
      compared with control rats. The administration of 1,25-dihydroxyvitamin D3 (1,25
      (OH)2D3) to vitamin D-deficient rats increased the initial rate of Pi uptake as
      well as the amounts of NaPi-2 mRNA and protein in the juxtamedullary cortex. The
      transcriptional activity of a luciferase reporter plasmid containing the promoter
      region of the human type II Na+-dependent Pi transporter NaPi-3 gene was
      increased markedly by 1,25-(OH)2D3 in COS-7 cells expressing the human vitamin D
      receptor. A deletion and mutation analysis of the NaPi-3 gene promoter identified
      the vitamin D-responsive element as the sequence 5'-GGGGCAGCAAGGGCA-3'
      nucleotides -1977 to -1963 relative to the transcription start site. This element
      bound a heterodimer of the vitamin D receptor and retinoid X receptor, and it
      enhanced the basal transcriptional activity of the promoter of the herpes simplex
      virus thymidine kinase gene in an orientation-independent manner. Thus, one
      mechanism by which vitamin D regulates Pi homeostasis is through the modulation
      of the expression of type II Na+-dependent Pi transporter genes in the
      juxtamedullary kidney cortex.

PMID- 9603975
TI  - Inhibitory effects of expanded GAA.TTC triplet repeats from intron I of the
      Friedreich ataxia gene on transcription and replication in vivo.
AB  - Friedreich ataxia (FRDA) is associated with the expansion of a GAA. TTC triplet
      repeat in the first intron of the frataxin gene, resulting in reduced levels of
      frataxin mRNA and protein. To investigate the mechanisms by which the intronic
      expansion produces its effect, GAA.TTC repeats of various lengths (9 to 270
      triplets) were cloned in both orientations in the intron of a reporter gene.
      Plasmids containing these repeats were transiently transfected into COS-7 cells.
      A length- and orientation-dependent inhibition of reporter gene expression was
      observed. RNase protection and Northern blot analyses showed very low levels of
      mature mRNA when longer GAA repeats were transcribed, with no accumulation of
      primary transcript. Replication of plasmids carrying long GAA.TTC tracts
      (approximately 250 triplets) was greatly inhibited in COS-7 cells compared with
      plasmids carrying (GAA.TTC)9 and (GAA.TTC)90. Replication inhibition was five
      times greater for the plasmid whose transcript contains (GAA)230 than for the
      plasmid whose transcript contains (UUC)270. Our in vivo investigation revealed
      that expanded GAA.TTC repeats from intron I of the FRDA gene inhibit
      transcription rather than post-transcriptional RNA processing and also interfere
      with replication. The molecular basis for these effects may be the formation of
      non-B DNA structures.

PMID- 9603974
TI  - Molecular cloning and expression of GDP-D-mannose-4,6-dehydratase, a key enzyme
      for fucose metabolism defective in Lec13 cells.
AB  - Subsets of mammalian cell surface oligosaccharides contain specific fucosylated
      moieties expressed in lineage- and/or temporal-specific patterns. The functional
      significance of these fucosylated structures is incompletely defined, although
      there is evidence that subsets of them, represented by the sialyl Lex
      determinant, are important participants in leukocyte adhesion and trafficking
      processes. Genetic deletion of these fucosylated structures in the mouse has been
      a powerful tool to address functional questions about fucosylated glycans.
      However, successful use of such approaches can be problematic, given the
      substantial redundancy in the mammalian alpha-1,3-fucosyltransferase and alpha
      1,2-fucosyltransferase gene families. To circumvent this problem, we have chosen
      to clone the genetic locus encoding a mammalian GDP-D-mannose-4,6-dehydratase
      (GMD). This enzyme generates GDP-mannose-4-keto-6-D-deoxymannose from GDP
      mannose, which is then converted by the FX protein (GDP-4-keto-6-D-deoxymannose
      epimerase/GDP-4-keto-6-L-galactose reductase) to GDP-L-fucose. GMD is thus
      imperative for the synthesis of all fucosylated oligosaccharides. An expression
      cloning approach and the GMD-deficient CHO host cell line Lec13 were used to
      generate a population of cDNA molecules enriched in GMD cDNAs. This enriched
      plasmid population was then screened using a human expressed sequence tag (EST
      AA065072) with sequence similarity to an Arabidopsis thaliana GMD cDNA. This
      approach, together with 5'-rapid amplification of cDNA ends, yielded a human cDNA
      that complements the fucosylation defect in the Lec13 cell line. Northern blot
      analyses indicate that the GMD transcript is absent in Lec13 cells, confirming
      the genetic deficiency of this locus in these cells. By contrast, the transcript
      encoding the FX protein, which forms GDP-L-fucose from the ketosugar intermediate
      produced by GMD, is present in increased amounts in the Lec13 cells. These
      results suggest that metabolites generated in this pathway may participate in the
      transcriptional regulation of the FX protein and possibly the GMD protein. The
      results also suggest that the genomic structure encoding GMD in Lec13 cells
      likely has a defect different from a point mutation in the coding region.

PMID- 9603976
TI  - Enhanced binding of azidothymidine-resistant human immunodeficiency virus 1
      reverse transcriptase to the 3'-azido-3'-deoxythymidine 5'-monophosphate
      terminated primer.
AB  - Human immunodeficiency virus type 1 is resistant to 3'-azido-3'-deoxythymidine
      (AZT) when four amino acid substitutions (D67N, K70R, T215F, and K219Q) are
      present simultaneously in its reverse transcriptase. Wild-type and AZT-resistant
      reverse transcriptases show identical binding to a 3'-azido-3'-deoxythymidine 5'
      monophosphate (AZTMP)-terminated primer/RNA template. On DNA templates, the
      equilibrium dissociation constant (KD) for primer/template and AZT-resistant
      reverse transcriptase (RT) (KD = 4.1 nM) is similar to that of the wild-type
      enzyme (KD = 6.2 nM). However, koff is 4-25-fold lower for the AZT-resistant
      enzyme than for the wild-type enzyme, depending on the nucleotide and the
      template. The kinetic decay of a wild-type RT/primer/AZTMP-terminated DNA
      template complex is biphasic. Seventy percent of the initial complex decays with
      a rate constant greater than 0.05 s-1, and 30% with a rate constant of 0.0017 s
      1. Decay of an AZT-resistant RT/AZTMP-terminated primer/DNA template complex is
      monophasic, with a rate constant of 0.0018 s-1. The last two nucleotides at the
      3' end of the AZTMP-terminated DNA primer in complex with AZT-resistant RT, but
      not wild-type RT, and a DNA template are protected from exonuclease digestion,
      suggesting that enhanced binding of the 3' end of the AZTMP-terminated DNA primer
      to reverse transcriptase is involved in the mechanism of AZT resistance by human
      immunodeficiency virus type 1.

PMID- 9603977
TI  - The ATPase activity of Myr3, a rat myosin I, is allosterically inhibited by its
      own tail domain and by Ca2+ binding to its light chain calmodulin.
AB  - We purified Myr3 (third unconventional myosin from rat), a mammalian "amoeboid"
      subclass myosin I, from rat liver. The heavy chain of purified Myr3 is associated
      with a single calmodulin light chain. Myr3 exhibits K/EDTA-ATPase and Mg-ATPase
      activity. The Mg-ATPase activity is stimulated by increasing F-actin
      concentrations in a complex triphasic manner similar to the Mg-ATPase activity of
      myosin I molecules from protozoa. Although purified Myr3 was observed to cross
      link actin filaments, it bound in an ATP regulated manner to F-actin, and no
      evidence for a nucleotide-independent high affinity actin binding site that could
      explain the triphasic activation pattern was obtained. Micromolar concentrations
      of free Ca2+ reversibly inhibit the Mg-ATPase activity of Myr3 by binding to its
      light chain calmodulin, which remains bound to the Myr3 heavy chain irrespective
      of the free Ca2+ concentration. Polyclonal antibodies and Fab fragments directed
      against the tail domain were found to stimulate the Mg-ATPase activity. A similar
      stimulation of the Myr3 Mg-ATPase activity is observed upon proteolytic removal
      of the very C-terminal SH3 domain. These results demonstrate that Myr3 is subject
      to negative regulation by free calcium and its own tail domain and possibly
      positive regulation by a tail-domain binding partner.

PMID- 9603978
TI  - Autocrine/paracrine determinants of strain-activated brain natriuretic peptide
      gene expression in cultured cardiac myocytes.
AB  - The application of mechanical strain leads to activation of human brain
      natriuretic peptide gene promoter activity, a marker of hypertrophy, in cultured
      neonatal rat ventricular myocytes. We have used a combination of transient
      transfection analysis and reverse transcriptase-polymerase chain reaction to
      examine the role of locally produced factors in contributing to this activation.
      Conditioned media from strained, but not static, cultures led to a dose-dependent
      increase in human brain natriuretic peptide gene promoter activity. This increase
      was completely blocked by losartan or BQ-123, implying a role for angiotensin and
      endothelin as autocrine/paracrine mediators of the response to strain. Inclusion
      of the same antagonists in the cultures themselves led to only partial inhibition
      (approximately 60%), whereas inclusion of exogenous endothelin or angiotensin II
      resulted in amplification of the strain response. Angiotensin II and endothelin
      appear to be arrayed in series in the regulatory circuitry; the angiotensin
      response was blocked by BQ-123, whereas the endothelin response was unaffected by
      losartan. Mechanical strain was also shown to stimulate expression of the
      endogenous angiotensinogen, angiotensin-converting enzyme, and endothelin genes
      in this system. Collectively, these data indicate that locally generated
      angiotensin II and endothelin, acting in series, play an important
      autocrine/paracrine role in mediating strain-dependent activation of cardiac
      specific gene expression.

PMID- 9603979
TI  - RAP46 is a negative regulator of glucocorticoid receptor action and hormone
      induced apoptosis.
AB  - RAP46 was first identified by its ability to bind the glucocorticoid receptor. It
      has since been reported to bind several cellular proteins, including the anti
      apoptotic protein Bcl-2, but the biological significance of these interactions is
      unknown. Here we show that RAP46 binds the hinge region of the glucocorticoid
      receptor and inhibits DNA binding and transactivation by the receptor. We further
      show that overexpression of RAP46 in mouse thymoma S49.1 cells inhibits
      glucocorticoid-induced apoptosis. Conversely, glucocorticoid-induced apoptosis
      and transactivation were enhanced after treating S49.1 cells with the
      immunosuppressant rapamycin, which down-regulates cellular levels of BAG-1, the
      mouse homolog of RAP46. The effect of rapamycin can, however, be overcome by
      overexpression of RAP46. These results together identify RAP46 as a protein that
      controls glucocorticoid-induced apoptosis through its negative regulatory action
      on the transactivation property of the glucocorticoid receptor.

PMID- 9603980
TI  - Galpha12 and Galpha13 stimulate Rho-dependent tyrosine phosphorylation of focal
      adhesion kinase, paxillin, and p130 Crk-associated substrate.
AB  - We examined whether constitutively active mutants of the Galpha proteins Galpha12
      and Galpha13, which together comprise the G12 subfamily of Galpha proteins,
      induce Rho-dependent tyrosine phosphorylation of the focal adhesion proteins p125
      focal adhesion kinase, paxillin, and p130 Crk-associated substrate. We report
      that transient expression of the constitutively active mutants of Galpha12 or of
      Galpha13 in human embryonic kidney 293 cells stimulates tyrosine phosphorylation
      of a set of proteins of Mr of 110,000-130,000, 97,000, and 60,000-70,000. We
      identified p125 focal adhesion kinase, paxillin, and p130 Crk-associated
      substrate as prominent tyrosine-phosphorylated proteins in human embryonic kidney
      293 cells expressing constitutively active Galpha12 and Galpha13. In common with
      the increased tyrosine phosphorylation of these proteins mediated by mitogens
      acting through heptahelical receptors, the Galpha12- and Galpha13-mediated
      increase in tyrosine phosphorylation is blocked by cytochalasin D, which
      specifically disrupts the actin cytoskeleton, and by the Clostridium botulinum C3
      exoenzyme, which ADP-ribosylates and inactivates Rho. Our results support the
      hypothesis that Galpha12 and Galpha13 activate Rho and suggest that Galpha12 and
      Galpha13 may mediate the tyrosine phosphorylation of p125 focal adhesion kinase,
      paxillin, and p130 Crk-associated substrate.

PMID- 9603981
TI  - Molecular characterization of an anchor protein (AKAPCE) that binds the RI
      subunit (RCE) of type I protein kinase A from Caenorhabditis elegans.
AB  - Classical A kinase anchor proteins (AKAPs) preferentially tether type II protein
      kinase A (PKAII) isoforms to sites in the cytoskeleton and organelles. It is not
      known if distinct proteins selectively sequester regulatory (R) subunits of type
      I PKAs, thereby diversifying functions of these critical enzymes. In
      Caenorhabditis elegans, a single type I PKA mediates all aspects of cAMP
      signaling. We have discovered a cDNA that encodes a binding protein (AKAPCE) for
      the regulatory subunit (RCE) of C. elegans PKAICE. AKAPCE is a novel, highly
      acidic RING finger protein composed of 1,280 amino acids. It binds RI-like RCE
      with high affinity and neither RIIalpha nor RIIbeta competitively inhibits
      formation of AKAPCE.RCE complexes. The RCE-binding site was mapped to a segment
      of 20 amino acids in an N-terminal region of AKAPCE. Several hydrophobic residues
      in the binding site align with essential Leu and Ile residues in the RII
      selective tethering domain of prototypic mammalian AKAPs. However, the RCE
      binding region in AKAPCE diverges sharply from consensus RII-binding sites by
      inclusion of three aromatic amino acids, exclusion of a highly conserved Leu or
      Ile at position 8 and replacement of C-terminal hydrophobic amino acids with
      basic residues. AKAPCE.RCE complexes accumulate in intact cells.

PMID- 9603983
TI  - Activation by autophosphorylation or cGMP binding produces a similar apparent
      conformational change in cGMP-dependent protein kinase.
AB  - Binding of cyclic nucleotide to or autophosphorylation of cGMP-dependent protein
      kinase (PKG) activates this kinase, but the molecular mechanism of activation for
      either process is unknown. Activation of PKG by cGMP binding produces a
      conformational change in the enzyme (Chu, D.-M., Corbin, J. D., Grimes, K. A.,
      and Francis, S. H. (1997) J. Biol. Chem. 272, 31922-31928; Zhao, J., Trewhella,
      J., Corbin, J., Francis, S., Mitchell, R., Brushia, R., and Walsh, D. (1997) J.
      Biol. Chem. 272, 39129-31936). In the present studies, activation of type Ibeta
      PKG by either autophosphorylation or cGMP-binding alone causes (i) an
      electronegative charge shift on ion exchange chromatography, (ii) a similar
      increase ( approximately 3.5 A) in the Stokes radius as determined by gel
      filtration chromatography, and (iii) a similar decrease in the mobility of the
      enzyme on native gel electrophoresis. Consistent with these results, cGMP binding
      increases the rate of phosphoprotein phosphatase-1 catalyzed dephosphorylation of
      PKG which is autophosphorylated only at Ser-63 (not activated); however,
      dephosphorylation of PKG that is highly autophosphorylated (activated) is not
      stimulated by cGMP. The combined results suggest that activation of PKG by either
      autophosphorylation or cGMP binding alone produces a similar apparent elongation
      of the enzyme, implying that either process activates the enzyme by a similar
      molecular mechanism.

PMID- 9603982
TI  - Constitutive activation of endocytosis by mutation of myoA, the myosin I gene of
      Aspergillus nidulans.
AB  - Class I myosins function in cell motility, intracellular vesicle trafficking and
      endocytosis. Recently, it was shown that class I myosins are phosphorylated by a
      member of the p21-activated kinase (PAK) family. PAK phosphorylates a conserved
      serine or threonine residue in the myosin heavy chain. Phosphorylation at this
      site is required for maximal activation of the actin-activated Mg2+-ATPase
      activity in vitro. This serine or threonine residue is conserved in all known
      class I myosins of microbial origin and in the human and mouse class VI myosins.
      We have investigated the in vivo significance of this phosphorylation by mutating
      serine 371 of the class I myosin heavy chain gene myoA of Aspergillus nidulans.
      Mutation to glutamic acid, which mimics phosphorylation and therefore activation
      of the myosin, results in an accumulation of membranes in growing hyphae. This
      accumulation of membranes results from an activation of endocytosis. In contrast,
      mutation of serine 371 to alanine had no discernible effect on endocytosis. These
      studies are the first to demonstrate the in vivo significance of a regulatory
      phosphorylation on a class I myosin. Furthermore, our results suggest that MYOA
      has two functions, one dependent and one independent of phosphorylation.

PMID- 9603984
TI  - Regulation and function of DNA methylation in vertebrates.
AB  - In vertebrates, genomic DNA is often methylated at the 5th position of cytosine
      in the sequence of CpG, and this is the only chemical modification that genomic
      DNA of vertebrates allows under physiological conditions. During evolution,
      vertebrates acquired CpG methylation as a new tool for controlling gene
      expression in addition to the varieties of transcription factors. In mammals, the
      methylation pattern of genomic DNA is erased and reset in germ line and at the
      early stage of embryogenesis. Maintenance-type methylation activity ensures
      clonal transmission of the lineage-specific methylation pattern in somatic cells.
      The methylation pattern is dynamic and changes during cell differentiation. Prior
      to the expression of tissue-specific genes, specific sites of the promoters are
      demethylated. In general, the methylation of a gene suppresses its expression.
      However, not much is known about the mechanisms that regulate the methylation
      state and the gene expression by DNA methylation.

PMID- 9603985
TI  - Sequence-function relationships of prokaryotic and eukaryotic
      galactosyltransferases.
AB  - Galactosyltransferases are enzymes which transfer galactose from UDP-Gal to
      various acceptors with either retention of the anomeric configuration to form
      alpha1,2-, alpha1,3-, alpha1,4-, and alpha1, 6-linkages, or inversion of the
      anomeric configuration to form beta1, 3-, beta1,4-, and beta1-ceramide linkages.
      During the last few years, several (c)DNA sequences coding for
      galactosyltransferases became available. We have retrieved these sequences and
      conducted sequence similarity studies. On the basis of both the nature of the
      reaction catalyzed and the protein sequence identity, these enzymes can be
      classified into twelve groups. Using a sensitive graphics method for protein
      comparison, conserved structural features were found in some of the
      galactosyltransferase groups, and other classes of glycosyltransferases,
      resulting in the definition of five families. The lengths and locations of the
      conserved regions as well as the invariant residues are described for each
      family. In addition, the DxD motif that may be important for substrate
      recognition and/or catalysis is demonstrated to occur in all families but one.

PMID- 9603986
TI  - Mitochondria-targeting sequence, a multi-role sorting sequence recognized at all
      steps of protein import into mitochondria.
AB  - The intracellular sorting of newly synthesized precursor proteins (preproteins)
      to mitochondria depends on the "mitochondria-targeting sequence" (MTS), which is
      located at the amino termini of the preproteins. MTS is required, however, not
      only for targeting newly synthesized preproteins to mitochondria, but also for
      all the following steps along the mitochondrial protein import pathway. MTS of
      nascent preproteins is first recognized by a cytoplasmic molecular chaperone,
      MSF, and then by Tom70 and Tom20 of the mitochondrial outer membrane receptor
      complex, Tom5 and Tom40 of the outer membrane protein translocation machinery,
      Tim23 of the inner membrane protein translocation machinery, and finally the
      processing peptidase, MPP, in the matrix. MTS is a multi-role sorting sequence
      which specifically interacts with various components along the mitochondrial
      protein import pathway. Recognition of MTS at multiple steps during the import of
      preproteins may contribute to the strict sorting of proteins destined for
      mitochondria.

PMID- 9603987
TI  - Efficient induction of hepatocyte spheroids in a suspension culture using a water
      soluble synthetic polymer as an artificial matrix.
AB  - The preparation of hepatocyte spheroids by adding a water-soluble synthetic
      polymer as an artificial matrix was performed in a cell suspension system. Cell
      aggregation was promoted without cytotoxicity by adding Eudragit (a copolymer of
      methacrylic acid and methylmethacrylate) to the culture medium. Spheroid-like
      cell aggregates, whose liver functions were enhanced, were effectively formed in
      the presence of 0.1% Eudragit, independent of the cultural substratum. Moreover,
      the mass preparation of spheroids could be achieved with a high production yield
      by means of a suspension culture in a spinner flask. In this case, the polymer
      protected the cells from damage due to agitation. The spheroids induced with
      Eudragit expressed high liver functions, such as albumin secretion, ammonia
      removal, and urea synthesis. On histological observation, the spheroids showed a
      well-developed cell adhesion apparatus and bile canaliculi. In addition, a higher
      calcium ion concentration in the cells of spheroids was observed compared with in
      monolayer cells.

PMID- 9603988
TI  - VIP induces the translocation and degradation of the alpha subunit of Gs protein
      in rat pituitary GH4C1 cells.
AB  - It has been shown that G proteins are potential regulatory molecules in the
      transmembrane signaling cascade. The aim of this study was to examine the
      possibility of equivalent G-protein redistribution and/or down-regulation in a
      target cell upon agonist stimulation. Short-term (0-80 min) incubation of rat
      pituitary GH4C1 cells with vasoactive intestinal peptide (VIP, 0.1 microM)
      induced a decrease in the levels of Gsalpha in the membrane fraction, whereas
      immunoblot analysis and reconstitution assay of adenylyl cyclase clearly showed
      an increase in the amount of Gsalpha in the supernatant (cytosolic) fraction. The
      VIP-induced release of G proteins alpha subunits from membranes was specific for
      Gsalpha. The VIP-dependent release of Gsalpha from membranes was blocked by a VIP
      receptor antagonist, (N-Ac-Tyr,D-Phe)-GRF(1-29)-NH2 (10 microM). Pituitary
      adenylate cyclase-activating polypeptide (PACAP) also stimulated the release of
      Gsalpha from membranes of GH4C1 cells. Furthermore, prolonged exposure of cells
      to VIP (0.1 microM) for 2-24 h caused a 21-40% decrease in Gsalpha from membranes
      and a 6% increase in total Gsalpha in the cytosolic fraction. The effect of VIP
      was dose-dependent with ED50 values of 81.6+/-20.0 nM for down-regulation and
      2.5+/-0.3 nM for translocation of Gsalpha. Concurrent treatment of GH4C1 cells
      with VIP and cycloheximide indicated that suppression of protein synthesis de
      novo did not mimic the effect of VIP. Moreover, the chase experiment of 35S
      labeled Gsalpha clearly demonstrated a more rapid rate of decay in the cells
      maintained in the presence of the agonist. These data indicate that VIP-receptor
      activates Gsalpha protein and induces the release of Gsalpha from membranes along
      with its down-regulation in cellular levels.

PMID- 9603989
TI  - Existence of two isoforms of extracellular signal-regulated kinase in fish.
AB  - Full-length cDNAs for extracellular signal-regulated kinases (ERK1 and ERK2) were
      isolated from a carp ovary cDNA library. The deduced amino acid sequences of carp
      ERK1 (cERK1) and ERK2 (cERK2) exhibited high degrees of homology to the known
      sequences of the ERK group. Northern blot analysis showed that cERK1 mRNA was not
      expressed in a tissue-specific manner, though the level of expression of cERK2
      mRNA varied among tissues. Western blot analysis of the brain, kidney, and ovary
      confirmed the expression of cERK1 and cERK2 in carp. Our findings indicate that
      two isoforms of ERK, ERK1 and ERK2, exist in fish.

PMID- 9603990
TI  - Recognition of allylic substrates in Sulfolobus acidocaldarius geranylgeranyl
      diphosphate synthase: analysis using mutated enzymes and artificial allylic
      substrates.
AB  - We examined the substrate specificity of two mutated geranylgeranyl diphosphate
      synthases, I-9 and I-11, with respect to several artificial substrates. These
      mutated enzymes have replacements in the amino acid sequences from positions 170
      to 173, which are thought to be a part of the putative substrate binding region.
      The wild-type enzyme catalyzes the condensation of IPP with a series of (2E)-3
      methyl-2-alkenyl diphosphates to give products with carbon numbers between 14 and
      21. On the other hand, the mutated enzymes show lower activities for artificial
      substrates with short alkyl chains than those of the wild-type enzyme though the
      carbon numbers of the products are similar to those in the case of the wild-type.
      The mutated enzyme I-11 never accepts artificial substrates shorter than C8.
      Analysis of additional mutated enzymes revealed that the characteristics of the
      mutated enzymes arise from a few substitutions within positions 171 to 173. These
      results indicate that the amino acids in the positions 171 to173 of the
      geranylgeranyl diphosphate synthase from Sulfolobus acidocaldarius are involved
      in recognition of short allylic substrates, such as dimethylallyl diphosphate,
      but not in recognition of the chain length of the products.

PMID- 9603991
TI  - Enhancement of retroviral gene transduction on a dish coated with a cocktail of
      two different polypeptides: one exhibiting binding activity toward target cells,
      and the other toward retroviral vectors.
AB  - CH-296, a recombinant fragment of human fibronectin (FN) composed of the cell
      binding domain (C-domain), heparin-binding domain II (H-domain), and CS1 site,
      enhances the retrovirus-mediated gene transduction (GT) of hematopoietic stem
      cells. The RGD sequence in the C-domain is recognized by a variety of cell types
      through integrin VLA-5, and the LDV sequence in the CS1-site is recognized by
      integrin VLA-4. Retrovirus particles were also found to bind to the H-domain.
      Consequently, the CH-296 fragment can enhance GT through binding to both
      retrovirus particles and target cells that express integrins VLA-5 and/or VLA-4.
      In this study, we found that the GT efficiency can be maintained at levels
      comparable to that of CH-271, a FN fragment similar to CH-296 but lacking the CS1
      site, when a cocktail of separated functional domains of CH-271 is used. When a
      dish was coated with a mixture of the C-domain and H-domain (molar ratio, 1:10),
      the GT efficiency of NIH3T3 cells reached the same level as that of the mother
      fragment, CH-271. The H-domain in the cocktail can be replaced with other virus
      binding components, polylysine, FGF, and the insulin-binding domain of ColV,
      without the loss of GT efficiency. With other than FN fragments, a cocktail of
      erythropoietin and polylysine caused higher GT efficiency of Epo-receptor
      expressing TF-1 cells than in the case of each component alone.

PMID- 9603992
TI  - Two distinct upstream regions are involved in expression of the catalase gene in
      Schizosaccharomyces pombe in response to oxidative stress.
AB  - The DNA region responsible for the induction of the catalase gene of
      Schizosaccharomyces pombe in response to oxidative stress was determined by
      constructing a series of deletions in the 5'-flanking region of the gene. Cells
      having deletion -672 (numbered with the transcription start site as +1) to -111
      showed no significant difference in catalase expression from the wild-type cells.
      Cells having deletion -672 to -89 showed reduced basal expression of the catalase
      mRNA, but retained the ability of induction in response to oxidative stress.
      Cells having deletion -672 to -55 completely lost the ability to express the
      catalase mRNA. These results suggested that two regions, -89 to -55 and -111 to 
      89, are involved in expression of the catalase gene. The DNA region of -89 to -55
      overlapped with the Atf1 binding sequence. The Atf1 is a bZIP transcription
      factor with an important role in stress response under the control of the Spc1
      mitogen activated protein (MAP) kinase. Introduction of the atf1(-) or spc1(-)
      mutation into the mutant having a deletion in -672 to -89 completely abolished
      the expression of the catalase mRNA. This result indicated that the Spc1-Atf1
      cascade is involved in expression of the catalase gene through the region of -89
      to -55. In mutants spc1(-) and atf1(-), basal expression and induction by
      hydrogen peroxide of catalase mRNA were observed. These results revealed that not
      only the Atf1 binding site but also another DNA element independent of the Spc1
      Atf1 pathway is involved in the expression of the catalase gene in response to
      oxidative stress in S. pombe. Proteins that bound specifically to each DNA
      element existed in the cell extract of the wild-type S. pombe.

PMID- 9603993
TI  - Molecular characterization of the mouse mtprd gene, a homologue of human TPRD:
      unique gene expression suggesting its critical role in the pathophysiology of
      Down syndrome.
AB  - We and others recently isolated a human TPRD gene, possessing a motif of the
      tetratricopeptide repeat (TPR), from the Down syndrome-critical region (DCR) of
      chromosome 21q22.2. In this study, we isolated a mouse homologue of TPRD cDNA,
      mtprd, and examined its expression profile in mouse embryos. The gene was mapped
      to mouse chromosome 16C3.3-4, consistent with the location of DCR, and encodes
      1,979 amino acid residues with 76% identity to TPRD. The mtprd protein has three
      units of the TPR motif with 91% homology to TPRD. The protein also has two
      regions homologous to several matrix proteins with 86 and 70% identities to those
      of TPRD. Several splicing variants of the 5' portion of the open reading frame of
      mtprd were identified by RT-PCR and sequencing of mRNAs. In situ hybridization
      showed that mtprd is ubiquitously expressed in mouse embryos but predominantly in
      the central nervous system, including the telencephalon, mesencephalon, and
      metencephalon. These results suggest that the TPRD gene is one of the genes
      responsible for not only the morphological anomalies but also the neurological
      abnormalities observed in Down syndrome. The presence of splicing variants
      indicates that the protein may also have several isoforms in mice.

PMID- 9603995
TI  - Induction of apoptosis by phosphatidylserine.
AB  - Treatment of Chinese hamster ovary (CHO) cells with phosphatidylserine (PS)
      caused cell death in a dose-dependent manner. Other phospholipids, such as
      phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and
      phosphatidic acid, had no effect on cell viability. The cells incubated with PS
      became round and underwent a dramatic reduction of cellular volume while
      maintaining the membrane containment of cellular contents. The PS-treatment
      induced chromatin condensation and extensive DNA fragmentation, with a pattern
      characteristic of internucleosomal fragmentation on agarose gel electrophoresis.
      These results indicate that PS-treatment induces apoptosis of CHO cells. This
      apoptosis-inducing activity was highly specific for PS, and neither of the
      synthetic PS analogs 1,2-diacyl-sn-glycero-3-phospho-D-serine (D-PS) and 2,3
      diacyl-sn-glycero-1-phospho-L-serine induced apoptosis. Analysis using
      fluorescence-labeled phospholipids showed that both PS and D-PS were taken up
      equally and then transported to intracellular membranes, suggesting that the PS
      specific induction of apoptosis was not the result of its specific
      internalization. These observations suggest that certain molecules which may
      recognize the stereo-specific configuration of PS are involved in the apoptotic
      process triggered by PS.

PMID- 9603994
TI  - The roles of individual cysteine residues of Sendai virus fusion protein in
      intracellular transport.
AB  - The role of intramolecular disulfide bonds in the fusion (F) protein of Sendai
      virus was studied. The 10 cysteine residues were changed to serine residues using
      site-directed mutagenesis. None of the cysteine mutant F proteins reacted with a
      monoclonal antibody specific for the mature conformation of the F protein, but
      eight of ten mutants reacted with an immature conformation-specific monoclonal
      antibody. The transport of these mutant proteins to the cell surface was
      drastically reduced. All of the cysteine mutant F proteins remained sensitive to
      endoglycosidase H (endo H) for 3 h after their synthesis. Moreover, cell surface
      transport of the hemagglutinin-neuraminidase (HN) protein co-expressed with each
      of these cysteine mutant F proteins was also reduced. These results suggest that
      all cysteine residues participate in the formation of intramolecular disulfide
      bonds, that co-translational disulfide bond formation is crucial to the correct
      folding and intracellular transport of the F protein, and that interaction of the
      F and HN proteins takes place intracellulary.

PMID- 9603996
TI  - Intracellular localization of migration inhibitory factor-related protein (MRP)
      and detection of cell surface MRP binding sites on human leukemia cell lines.
AB  - The migration inhibitory factor-related proteins (MRPs) MRP-8 and MRP-14 were
      detected in differentiated human leukemia cell lines (THP-1 and HL-60) by
      immunocytochemical analysis. They were induced and colocalized in the cytoplasm
      and in lesser amounts in the nucleus when THP-1 and HL-60 cells were induced to
      differentiate by 1alpha,25-dihydroxyvitamin D3 or retinoic acid. In a search for
      a protein capable of binding MRPs, both MRPs were individually produced in insect
      cells (Sf21) infected with recombinant baculovirus. The purified recombinant MRPs
      were electrophoretically and antigenically indistinguishable from the native
      proteins, and their ability to form the MRP8/14 complex was retained. The
      presence of MRP binding sites was investigated by a binding assay using
      recombinant MRPs and specific monoclonal antibodies. MRP binding sites were
      detected on the cell membrane of the human leukemia cell lines THP-1, Raji, and
      MOLT-4. HL-60 cells treated with 1alpha, 25-dihydroxyvitamin D3 did not express
      MRP binding sites on the cell membrane, but a high level of MRPs accumulated in
      the cells. The occurrence of MRP binding sites on the cell surface of leukemia
      cell lines of monocyte and lymphocyte origin suggests that MRPs, released from
      neutrophils under certain conditions, may contribute to the activation and
      recruitment of effector cells to inflammatory lesions.

PMID- 9603997
TI  - Identification of genes affecting lycopene formation in Escherichia coli
      transformed with carotenoid biosynthetic genes: candidates for early genes in
      isoprenoid biosynthesis.
AB  - Although isopentenyl diphosphate is a precursor of isoprenoids in Escherichia
      coli, the genes and enzymes involved in its biosynthesis have not been
      identified. Thus, we tried to isolate E. coli mutants deficient in the
      biosynthesis and their complementary genes by use of an artificial phenotypic
      screening system employing three carotenoid biosynthetic genes, crtE, crtB, and
      crtI. Cells were mutagenized with ethylmethanesulfonate, then transformed with a
      plasmid for expression of the carotenogenic genes. Mutants deficient in
      biosynthesis of isopentenyl diphosphate were expected to form white colonies,
      because they are unable to produce enough lycopene, whereas wild-type cells form
      red colonies. Among large numbers of red colonies, we identified 117 white
      colonies. Next, we transformed each mutant with an E. coli genomic library.
      Twenty-nine complementary genes that restore red color of host colonies were
      isolated. A homology search and further complementation study using subcloned
      genes revealed that the true complementary genes encode isopentenyl diphosphate
      isomerase, subunits of ATP synthase, enzymes of the Krebs cycle, some aldehyde
      dehydrogenases, phosphate acetyltransferase, and enzymes which relate to the
      biosynthesis of ubiquinones and menaquinones. Two unknown genes were also found,
      designated elb1 and 2, which may be involved in the early steps of isoprenoid
      biosynthesis.

PMID- 9603998
TI  - Chemical modification of L-phenylalanine oxidase from Pseudomonas sp. P-501 by
      phenylglyoxal. Identification of one essential arginyl residue.
AB  - L-Phenylalanine oxidase from Pseudomonas sp. P-501 was irreversibly inactivated
      by the arginine-specific reagents, phenylglyoxal (PGO) and p-hydroxyphenylglyoxal
      (HPG). The inactivation by PGO and HPG follows pseudo-first-order kinetics with
      second-order rate constants of 10.6 and 15.1 M-1.min-1, respectively, and a
      single arginyl residue was modified specifically. The effective protection by
      substrate L-phenylalanine against the inactivation by these reagents strongly
      suggests that the arginyl residue is located in the substrate binding site.
      SDS/PAGE analysis of the enzyme modified with [14C]PGO revealed that the arginyl
      residue was in the beta subunit of the enzyme. The fragment containing the 14C
      labeled arginyl residue was purified from the enzymatic digests of the labeled
      beta subunit by HPLC and sequenced. The modification of Arg-35 in the beta
      subunit was identified. The sequence around Arg-35 shows homology to the
      corresponding regions of tryptophan-2-monooxygenases.

PMID- 9603999
TI  - Fluorescence resonance energy transfer between points on tropomyosin and actin in
      skeletal muscle thin filaments: does tropomyosin move?
AB  - Fluorescence resonance energy transfer (FRET) spectroscopy has been used to
      determine spatial relationships between residues on tropomyosin and actin in
      reconstituted muscle thin filament, and to detect a positional change of
      tropomyosin relative to actin on the thin filament in the presence and absence of
      Ca2+ ions. In addition to Cys-190 which is a single cysteine residue in rabbit
      skeletal muscle alpha-tropomyosin, a new site, Cys-87 which is a unique cysteine
      residue in a mutant alpha-tropomyosin, was labeled with a resonance energy donor
      molecule, 5-(2-iodoacetylaminoethyl)aminonaphthalene 1-sulfonic acid (IAEDANS).
      On the other hand, Gln-41, Lys-61, Cys-374, and the ATP-binding site of actin
      were selectively labeled with acceptor probes: fluorescein cadaverine,
      fluorescein 5-isothiocyanate, 4-dimethyl-aminophenylazophenyl 4'-maleimide, and
      TNP-ATP (or TNP-ADP), respectively. The distances between probes attached to
      position 87 of the mutant tropomyosin and Gln-41, Lys-61, Cys-374, or the
      nucleotide-binding site of actin on the reconstituted thin filament in the
      presence of Ca2+ ion were measured to be 43.2, 49.7, 45.4, and 35.2 A,
      respectively, and the distance between probes attached to position 190 of
      tropomyosin and Gln-41 or the nucleotide-binding site of actin were 51.6 and 43.1
      A, respectively. The transfer efficiencies between these donor and acceptor
      molecules were large, so that the efficiency should be very sensitive to changes
      in distance between probes attached to tropomyosin and actin. However, the
      transfer efficiency did not change appreciably upon removal of Ca2+ ions,
      suggesting that tropomyosin does not change its position on the reconstituted
      thin filament in response to a change in Ca2+ ion concentration. The present
      results do not support the notion of tropomyosin movement on skeletal muscle thin
      filaments as proposed in the steric blocking theory.

PMID- 9604000
TI  - Properties, sequence, and synthesis in Escherichia coli of 1-aminocyclopropane-1
      carboxylate deaminase from Hansenula saturnus.
AB  - The plant hormone ethylene is generated from a unique precursor, 1
      aminocyclopropane-1-carboxylate (ACC). In previous studies, ACC deaminase, which
      degrades ACC to alpha-ketobutyrate and ammonia, was found in four strains of
      Pseudomonas, characterized, and sequenced. To verify the wider distribution of
      ACC deaminase in microorganisms, we purified and sequenced ACC deaminase from the
      yeast Hansenula saturnus. The purified enzyme was active toward ACC, D-serine and
      dl-coronamic acid, indicating the same stereospecificity as the Pseudomonas
      enzyme, but unlike the bacterial enzyme it was not active toward beta-chloro-D
      alanine and O-acetyl-D-serine. Analyses of peptides from proteolytic digests of
      the purified and modified ACC deaminase covered more than 90% of its amino acid
      sequence and showed a blocked N-terminal residue as N-acetylserine. A cDNA
      encoding the ACC deaminase was isolated from H. saturnus cells incubated in alpha
      aminoisobutyrate medium, and sequenced. The yeast enzyme has 441 amino acid
      residues, of which 60 to 63% are identical to those of reported Pseudomonas
      enzymes. The open reading frame encoding ACC deaminase was subcloned into pET-11d
      and expressed in Escherichia coli BL21 (DE3) as an active enzyme.

PMID- 9604001
TI  - Changes of gene expression by lysophosphatidylcholine in vascular endothelial
      cells: 12 up-regulated distinct genes including 5 cell growth-related, 3
      thrombosis-related, and 4 others.
AB  - Lysophosphatidylcholine (lysoPC), a component of oxidatively modified
      lipoproteins, is present in atherosclerotic lesions, and its proatherogenic
      properties have been demonstrated. To gain an insight into lysoPC-mediated
      endothelial gene expression, we applied nonradioactive differential display
      analysis of mRNA from lysoPC-treated and untreated human umbilical vein
      endothelial cells. We identified 12 up-regulated distinct genes including 5 cell
      growth-related genes (two phosphatases CL100 and B23/hVH-3, gravin, activating
      transcription factor-4, and heparin-binding epidermal growth factor-like growth
      factor), 3 thrombosis-related genes (plasminogen activator inhibitor-1, tissue
      plasminogen activator, and thrombomodulin), and 4 others (stanniocalcin, NAD
      dependent methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate
      cyclohydrolase, BENE, and reducing agents and tunicamycin-responsive protein). We
      isolated a full-length cDNA of human gravin. The cDNA sequence of gravin was
      homologous with rat mitogenic regulatory gene or rat protein kinase C binding
      protein and substrate, suggesting that gravin would regulate cell growth. Thus,
      lysoPC apparently accelerates atherosclerosis by regulating the expression of a
      wide variety of genes. Our data suggest the involvement in atherogenesis of the
      genes hitherto regarded as atherosclerosis-unrelated.

PMID- 9604003
TI  - Cyanocysteine-mediated molecular dissection of dihydrofolate reductase:
      occurrence of intra- and inter-molecular reactions forming a peptide bond.
AB  - During a cyanocysteine-mediated dissection study of dihydrofolate reductase, a
      peptide fragment with a molecular mass of 18 Da less than expected was found as a
      major reaction product when the dissection reaction was applied to a Lys
      cyanocysteine linkage. Detailed characterization of the dissection products by
      protease digestion, peptide sequencing, liquid chromatography/electrospray
      ionization mass spectrometry, and capillary electrophoresis suggested that the by
      product was generated via a lactam ring formation through the intramolecular
      nucleophilic attack of the epsilon-amino group on the carbonyl carbon of the Lys
      cyanocysteine linkage. We have also demonstrated the occurrence of intermolecular
      attack of an alpha-amino group of glycine on the carbonyl carbon of the X
      cyanocysteine linkage to form a new X-Gly linkage, which should be a useful
      reaction for specific modification of proteins at the C-terminal.

PMID- 9604002
TI  - Clusters of basic amino acids in midkine: roles in neurite-promoting activity and
      plasminogen activator-enhancing activity.
AB  - The removal of N-terminally located clusters of basic amino acids (N-tail) or C
      terminally located clusters of basic amino acids (C-tail) from the midkine (MK)
      molecule severely reduced its neurite-promoting activity. However, experiments
      involving chemically synthesized MK derivatives revealed that the roles of the N
      tail and C-tail were mostly indirect ones, i.e. they probably maintain the steric
      arrangements of the N-terminal and C-terminal halves. In particular, the C
      domain, which is the C-terminal half devoid of the C-tail, retained considerable
      neurite-promoting activity when it was uniformly coated on a dish. The removal of
      the N-tail or C-tail also reduced the enhancing activity of plasminogen activator
      (PA) in aortic endothelial cells, although the effect was lower. There are two
      heparin-binding sites in the C-domain, Clusters I and II. A mutation in Cluster I
      [R78-->Q] affected the PA-enhancing activity only slightly, and a mutation in
      Cluster II [K83K84-->QQ] abolished the activity, while both mutations are known
      to reduce the neurite-promoting activity moderately. Therefore, the two heparin
      binding sites in the C-domain play different roles in these two activities.
      Indeed, heparin exhibited different effects on these two activities. We also
      observed that intact MK was required for ordered neurite-promotion along the path
      of MK; one possible interpretation of this is that the N-terminal half is
      necessary for the stability of the molecule. Furthermore, K76 and K99 were found
      to be required for the secretion of MK; i.e. mutants in which one of these K
      residues was changed to Q were produced in the host cells, but not found in the
      medium.

PMID- 9604004
TI  - Contribution of tryptophan residues to the structural changes in perfringolysin O
      during interaction with liposomal membranes.
AB  - Perfringolysin O (theta-toxin) is a cholesterol-binding and pore-forming toxin
      that shares with other thiol-activated cytolysins a highly conserved sequence,
      ECTGLAWEWWR (residues 430-440), near the C-terminus. To understand the membrane
      insertion and pore-forming mechanisms of the toxin, we evaluated the contribution
      of each Trp to the toxin conformation during its interaction with liposomal
      membranes. Circular dichroism (CD) spectra of Trp mutant toxins indicated that
      only Trp436 has a significant effect on the secondary structure, and that Trp436,
      Trp438, and Trp439 make large contributions to near-UV CD spectra. Quenching the
      intrinsic Trp fluorescence of the wild-type and mutant toxins with brominated
      lecithin/cholesterol liposomes revealed that Trp438 and probably Trp436, but not
      Trp439, contributes to toxin insertion into the liposomal membrane. Near-UV CD
      spectra of the membrane-associated mutant toxins indicated that both Trp438 and
      Trp439 are required for the CD peak shift from 292 to 300 nm, a signal related to
      theta-toxin oligomerization and/or pore formation, suggesting a conformational
      change around Trp438 and Trp439 in these processes.

PMID- 9604005
TI  - Properties of glutamate racemase from Bacillus subtilis IFO 3336 producing poly
      gamma-glutamate.
AB  - We found glutamate racemase activity in cell extracts of Bacillus subtilis IFO
      3336, which abundantly produces poly-gamma-glutamate. The highest activity was
      obtained in the early stationary phase of growth. The racemase was purified to
      homogeneity. The enzyme was a monomer with a molecular mass of about 30 kDa and
      required no cofactor. It almost exclusively catalyzed the racemization of
      glutamate; other amino acids, including alanine and aspartate but not
      homocysteinesulfinate, were inactive as either substrates or inhibitors. Although
      the Vmax value of the enzyme for L-glutamate is 21-fold higher than that for D
      glutamate, the Vmax/Km value for L-glutamate is almost equal to that for the D
      enantiomer. The racemase gene, glr, was cloned into Escherichia coli cells and
      sequenced. The racemase was overproduced in the soluble fraction of the E. coli
      clone cells with the substitution of ATG for TTG, the initial codon of the glr
      gene. D-Amino acid aminotransferase activity was not detected in Bacillus
      subtilis IFO 3336 cells. B. subtilis CU741, a leuC7 derivative of B. subtilis
      168, showed lower glutamate racemase activity and lower productivity of poly
      gamma-glutamate than B. subtilis IFO 3336. These results suggest that the
      glutamate racemase is mainly concerned in D-glutamate synthesis for poly-gamma
      glutamate production in B. subtilis IFO 3336.

PMID- 9604006
TI  - Development-dependent expression of complex-type sugar chains specific to mouse
      brain.
AB  - We previously detected a fucosylagalactobiantenna with a bisecting GlcNAc residue
      (BA-2) and one lacking the GlcNAc residue linked to the Manalpha1-3 residue of BA
      2 (BA-1), which were enriched specifically in mouse brain [Shimizu, H., Ochiai,
      K., Ikenaka, K., Mikoshiba, K., and Hase, S. (1993) J. Biochem. 114, 334-338].
      Pyridylamino sugar chains were prepared from mouse brains of various ages, and BA
      1 and BA-2 were quantified after separation by HPLC. In cerebrum, BA-1 was
      scarcely expressed in newborn brain but gradually increased in amount during
      development, while expression of BA-2 reached a maximum 1 week after birth
      followed by a rapid decrease; in adult mice, the amount of BA-1 was almost the
      same as that of BA-2. In cerebellum, expression of BA-1 was lower than that of BA
      2 at all stages. Glycoproteins with the BA-1 and BA-2 structures were enriched in
      the membrane fraction, and the glycoproteins solubilized were purified by lectin
      affinity chromatography and gel filtration. The results indicated that BA-1 and
      BA-2 occurred in glycoproteins of more than 20 kDa in cerebellum, but most BA-1
      and BA-2 were found in a 80-200 kDa fraction in cerebrum. These results show that
      the two brain-specific sugar chains are developmentally regulated and linked to
      the membrane-associated glycoproteins of subcellular organellas.

PMID- 9604007
TI  - Flagellin-containing membrane vesicles excreted from Vibrio alginolyticus mutants
      lacking a polar-flagellar filament.
AB  - Polar flagellum-defective mutants (Pof- Laf-) have been isolated from a lateral
      flagella-defective mutant (Pof+ Laf-). Among these Pof- Laf- mutants, polar
      filamentless mutants, which have the hook structure but not the filament, were
      identified by electron microscopy. Their hooks were covered with a sheath
      structure which is contiguous to the outer membrane. The filament proteins,
      flagellins, were shed into the culture medium of these mutants. These flagellins
      could be sedimented by high-speed centrifugation even after heat or low pH
      treatment whereas the depolymerized flagellin of the Pof+ strain was degraded by
      these treatments. After Triton X-100 treatment, most flagellin of the
      filamentless mutants could no longer be sedimented, and was degraded. We observed
      vesicle-like structures on the tips of the hooks and in the flagellin fraction
      sedimented by high speed centrifugation. These results suggest that flagellin of
      the filamentless mutants is not assembled into the tip of the hook, but is
      excreted together with a membrane structure which is probably the sheath of polar
      flagella.

PMID- 9604008
TI  - Functional interactions between nuclear receptors recognizing a common sequence
      element, the direct repeat motif spaced by one nucleotide (DR-1).
AB  - Direct repeat motifs composed of two hexamer half-sites spaced by a single
      nucleotide (DR-1) are recognized by several members of the nuclear hormone
      receptor superfamily. We examined, by means of gene transfection assays, the
      interplay between the DR-1-binding nuclear receptors commonly expressed in liver,
      peroxisome proliferator-activated receptor alpha (PPARalpha), hepatocyte nuclear
      factor-4 (HNF-4), and chicken ovalbumin upstream transcription factor I (COUP
      TFI). Both PPARalpha and HNF-4 efficiently bound to the acyl-CoA oxidase gene
      enhancer element, but PPARalpha exhibited much stronger transactivation than HNF
      4. As a result, HNF-4 suppressed the gene-activating function of PPARalpha, when
      they were expressed together, due to competition for a common binding site. On
      the other hand, HNF-4, but not PPARalpha, effectively bound to the apolipoprotein
      CIII gene element, and activated gene transcription. PPARalpha had no effect even
      when co-expressed with HNF-4. COUP-TFI bound to both elements, and suppressed the
      gene activation by PPARalpha and HNF-4. Thus, these nuclear receptors have
      individual functions in gene regulation, and exhibit complex compound effects
      when they co-exist.

PMID- 9604009
TI  - Diversity of the troponin C genes during chordate evolution.
AB  - To elucidate the diversity of troponin C (TnC) during chordate evolution, we
      determined the organization of TnCs from the amphioxus, the lamprey, and the
      frog. Like the ascidian, the amphioxus possesses a single gene of TnC, and the
      fundamental gene structure is identical with the ascidian TnC. However, because
      alternative splicing does not occur in amphioxus, the potential for generation of
      TnC isoforms through this event arises only in the ascidian lineage. From the
      frog Xenopus laevis, two distinct cDNAs encoding fTnC isoforms and a single
      s/cTnC cDNA were determined. The duplication of the fTnC gene may be a character
      of only Xenopus or closely related species. The lamprey possesses two cDNAs each
      encoding fTnC and s/cTnC. The lamprey is the earliest diverged species among
      vertebrates, and thus it is supposed that the presence of both fTnC and s/cTnC is
      universal among vertebrate species, and that the gene duplication might have
      occurred at a vertebrate ancestor after the protochordate/vertebrate divergence.
      The position of the 4th intron is 3.24/0 in protochordate TnC genes, but at 3.
      11/2 in vertebrate fTnCs and s/cTnCs. It is suggested that the 4th intron sliding
      might have occurred prior to the gene duplication.

PMID- 9604010
TI  - Multiple DNA elements for sterol regulatory element-binding protein and NF-Y are
      responsible for sterol-regulated transcription of the genes for human 3-hydroxy-3
      methylglutaryl coenzyme A synthase and squalene synthase.
AB  - The expression of the human SREBP-2 gene is transcriptionally regulated in a
      cooperative manner by sterol regulatory element-binding proteins (SREBPs) and the
      general transcription factor NF-Y [Sato, R., Inoue, J., Kawabe, Y., Kodama, T.,
      Takano, T., and Maeda, M. (1996) J. Biol. Chem. 271, 26461-26464]. To understand
      the sterol-dependent transcriptional regulation by these factors in detail, we
      have examined the regulation of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG
      CoA) synthase and squalene synthase genes, whose promoters have multiple
      potential sterol regulatory elements (SRE, SREBP binding site) and NF-Y binding
      sites. The promoter of the human HMG CoA synthase gene was cloned, sequenced, and
      functionally characterized by means of reporter gene assays. The results indicate
      that an inverted CCAAT box, two SRE motifs and two Sp1 sites localized in a 90-bp
      region coordinately regulate the transcription. In the case of the human squalene
      synthase promoter, two SRE motifs and an inverted CCAAT box between the motifs
      localized in a 51-bp region are responsible for the sterol-regulated
      transcription of the gene. Gel mobility shift assay reveals that these two
      inverted CCAAT boxes are recognized by NF-Y. The involvement of multiple
      responsive elements in the transcription of HMG CoA synthase and squalene
      synthase seems to induce a higher level of sterol-dependent regulation (3.5 to 5.
      8-fold) compared with that of the SREBP-2 promoter, which contains a single pair
      of SRE motif and CCAAT box (1.8 to 2.6-fold). Reporter gene assays using
      constructs containing various nucleotide spacing lengths between the SRE motif
      and the CCAAT box demonstrate that the 16 to 20-bp spacing range is required for
      maximal transcriptional regulation. These results agree with the findings that
      the distances between the two motifs in the known sterol responsive elements in
      several genes, including the human HMG CoA synthase and squalene synthase genes,
      are in this range.

PMID- 9604011
TI  - Evidence for involvement of two isoforms of Syk protein-tyrosine kinase in signal
      transduction through the high affinity IgE receptor on rat basophilic leukemia
      cells.
AB  - Recent evidence suggests a critical role for Syk in mast cell activation upon
      high affinity IgE receptor (FcepsilonRI) aggregation. A rat basophilic leukemia
      cell line, RBL-2H3, expresses similar levels of two Syk isoforms that differ with
      respect to the presence of a 23-amino acid insert within the "linker" region
      located between the second Src homology 2 and the catalytic domain. Although they
      exhibit comparable intrinsic enzymatic activity, functional differences between
      the two isoforms are unknown. Here we report that the deleted Syk isoform can
      mediate signal transduction in RBL-2H3 cells. Aggregation of chimeric kinase,
      consisting of either form of Syk fused to the transmembrane and extracellular
      domains of guinea pig type II IgG Fc receptor, on RBL transfectants resulted in
      degranulation, release of leukotrienes, and enhanced gene expression of tumor
      necrosis factor-alpha. The chimeras as well as phospholipase C-gamma1 and Vav
      became tyrosine-phosphorylated upon aggregation of chimeras. We also found that
      both Syk isoforms from transiently transfected COS-7 cells were capable of
      binding to phosphorylated FcepsilonRI, and their kinase activities were similarly
      up-regulated in the presence of tyrosine-phosphorylated synthetic peptides based
      on the sequence of the gamma subunit of FcepsilonRI. Thus, these results
      establish that both isoforms of Syk can mediate signal transduction in mast cells
      and suggest that the 23-amino acid insert in the linker region of Syk may not be
      obligatory for FcepsilonRI signaling.

PMID- 9604012
TI  - Glycolaldehyde-modified low density lipoprotein leads macrophages to foam cells
      via the macrophage scavenger receptor.
AB  - It was shown that proteins modified with advanced glycation end products (AGE)
      are effectively endocytosed by macrophages or macrophage-derived cells in vitro,
      and immunohistochemical studies involving anti-AGE antibodies demonstrated the
      accumulation of AGE-modified proteins (AGE-proteins) in macrophage-derived foam
      cells in human atherosclerotic lesions in situ, suggesting the involvement of AGE
      modified LDL in the atherogenic process in vivo. To examine this suggestion, LDL
      was modified with glycolaldehyde, a highly reactive intermediate of the Maillard
      reaction. Physicochemically, glycolaldehyde-modified LDL (GA-LDL) was
      characterized by increases in negative charge, fluorescence intensity, and
      reactivity to anti-AGE antibodies, properties highly similar to those of AGE
      proteins. The cellular interaction of GA-LDL with mouse peritoneal macrophages
      showed that GA-LDL was specifically recognized and endocytosed, followed by
      lysosomal degradation. The endocytic uptake of GA-LDL by these cells was
      competitively inhibited by acetylated LDL (acetyl-LDL), and the endocytic
      degradation of acetyl-LDL was also competed for by GA-LDL. Furthermore,
      incubation of GA-LDL with these macrophages and Chinese hamster ovary cells
      overexpressing the macrophage scavenger receptor (MSR), but not with peritoneal
      macrophages from MSR-knockout mice, led to the intracellular accumulation of
      cholesteryl esters (CE). These results raised the possibility that AGE-modified
      LDL, if available in situ, is taken up by macrophages mainly via MSR and then
      contributes to foam cell formation in early atherosclerotic lesions.

PMID- 9604013
TI  - Further support for disabled students and veterinarians.

PMID- 9604014
TI  - Concerns regarding retrospective study of reported scrapie in sheep.

PMID- 9604015
TI  - Are nylon ties guaranteed?

PMID- 9604016
TI  - Response to letter regarding vaccination of cats.

PMID- 9604017
TI  - Response to letter regarding vaccination of cats.

PMID- 9604018
TI  - Feasibility of international somatic cell count standards.

PMID- 9604019
TI  - What is your diagnosis? Focal osteolysis involving the third and fourth
      metacarpal bones.

PMID- 9604020
TI  - Theriogenology question of the month. Azoospermia associated with 79,XXY
      chromosome complement (canine Klinefelter's syndrome).

PMID- 9604021
TI  - Expenditures of US pet-owning households for veterinary medical products and
      services purchased from veterinarians, 1987 to 1996.

PMID- 9604022
TI  - Public awareness of rabies and compliance with pet vaccination laws in
      Connecticut, 1993.
AB  - OBJECTIVE: To determine the degree of public awareness of rabies and compliance
      with cat and dog vaccination laws in Connecticut in 1993. DESIGN: Monthly
      telephone surveys. SAMPLE POPULATION: 1,810 households. PROCEDURE: A telephone
      interview was conducted, using rables-related questions contained in the
      Behavioral Risk Factor Surveillance System, with an adult member from households
      randomly selected statewide by telephone number. Results of the surveys for the
      year were aggregated, and weighted data were analyzed. RESULTS: Ninety percent of
      respondents had heard about rabies during the preceding year, and 84% considered
      it a problem in Connecticut. Forty-seven percent of households surveyed owned
      dogs or cats. Ninety-three percent of dogs and 80% of cats were reported to be
      vaccinated against rabies. Twenty-two percent of households with cats had at
      least 1 cat that was not current on rabies vaccination. CLINICAL RELEVANCE: In
      Connecticut, an epizootic of rabies in raccoons was accompanied by a high degree
      of awareness of rabies and rate of reported vaccination of dogs and cats.
      However, vaccination of cats was less common than that of dogs. Public education
      efforts should emphasize the necessity to vaccinate cats and to avoid contact
      with unknown cats in rabies epizootic or enzootic areas. A surveillance system
      can be used to help evaluate public health programs.

PMID- 9604023
TI  - Reliability of the hip distraction index in two-month-old German shepherd dogs.
AB  - OBJECTIVE: To determine whether distraction index (DI), a measure of passive hip
      joint laxity, at 2 months of age was predictive of DI at 4 or 12 months of age in
      German Shepherd Dogs. DESIGN: Prospective cohort study. ANIMALS: 45 German
      Shepherd Dogs. PROCEDURE: DI was measured at 2, 4, and 12 months of age. At the
      same times, a standard ventrodorsal radiographic projection of the pelvis with
      the hip joints extended was obtained and examined for evidence of degenerative
      joint disease (DJD). To facilitate radiographic positioning, dogs were sedated or
      anesthetized. RESULTS: DI at 2 months of age was not significantly correlated
      with DI at 4 or 12 months of age. However, DI at 4 months of age was correlated
      with DI at 12 months of age. The proportion of dogs with DI > or = 0.3 at 12
      months of age that had radiographic evidence of DJD by 12 months of age (13/22;
      59%) was significantly greater than the proportion of dogs with DI < 0.3 at 12
      months of age that had radiographic evidence of DJD by 12 months of age (1/9;
      11%). CLINICAL IMPLICATIONS: For German Shepherd Dogs, DI at 2 months of age was
      not sufficiently reliable to predict DI at 4 and 12 months of age; however, DI at
      4 and 12 months of age were comparable. We recommend that, for German Shepherd
      Dogs, DI not be measured before 4 months of age and that particularly for
      breeding dogs, DI be remeasured after maturity to confirm DI obtained at earlier
      ages. Studies including other breeds of dogs should be done to determine the
      youngest reliable age to initiate hip joint screening.

PMID- 9604024
TI  - Effect of storage conditions on cortisol, total thyroxine, and free thyroxine
      concentrations in serum and plasma of dogs.
AB  - OBJECTIVE: To determine for dogs stability of cortisol, thyroxine (T4), and free
      thyroxine (fT4) in plasma and serum stored in glass or plastic tubes at -20, 4,
      25, and 37 C. DESIGN: Prospective study. ANIMALS: Phase I, 7 Greyhounds; Phase
      II, 6 mixed-breed dogs. PROCEDURE: Phase I: blood was obtained after
      administration of thyroid-stimulating hormone and adrenocorticotropin. Serum and
      plasma samples from each dog were divided into 8 aliquots, 4 in glass and 4 in
      plastic tubes. A pair of aliquots, 1 in plastic and 1 in glass, were stored at 
      20, 4, 25, or 37 C for 5 days and then assayed for hormones. Phase II: blood was
      obtained without prior stimulation. For fT4 determination, serum from each dog
      was placed in plastic or glass tubes, assayed immediately, stored at -20 C for 5
      days, and reassayed. Aliquots from each dog were also stored for 1 day at 4 or 25
      C and then assayed. Samples for cortisol determination were handled as in phase
      I. RESULTS: Phase I: there was no effect of tube type (glass vs plastic) on
      cortisol. Cortisol concentrations decreased after storage in serum at 4, 25, and
      37 C, and in plasma at 37 C, compared with storage at -20 C. There was no effect
      of sample type (serum or plasma) on T4. Thyroxine concentrations increased after
      storage at 37 C in glass, compared with storage at -20 C. The fT4 concentrations
      were lower in serum than plasma after storage at -20 C. Concentrations of fT4
      increased after storage at 37 C in glass, compared with storage at -20 C. Phase
      II: the fT4 concentrations did not change after storage in any condition. There
      was no effect of tube type on cortisol concentrations. Serum cortisol
      concentrations decreased after storage at 37 C, compared with storage at -20 C.
      CLINICAL IMPLICATIONS: For cortisol, cooling of plasma is not necessary, but
      serum should be shipped cold. For T4 and fT4, serum is sufficient; contained
      within plastic tubes, samples can be shipped without cooling if assayed within 5
      days.

PMID- 9604025
TI  - Comparison of serum cortisol concentrations in clinically normal dogs after
      administration of freshly reconstituted versus reconstituted and stored frozen
      cosyntropin.
AB  - OBJECTIVE: To evaluate the biological stability of reconstituted cosyntropin
      after storage at -20 C for 2, 4, and 6 months. DESIGN: Prospective study.
      ANIMALS: 10 clinically normal dogs. PROCEDURE: Serum cortisol concentrations in
      dogs were determined before and 1 hour after administration of freshly
      reconstituted cosyntropin (synthetic ACTH) or cosyntropin that had been
      reconstituted and stored frozen at -20 C in plastic syringes for 2, 4, and 6
      months. Cosyntropin was administered at 5 micrograms/kg (2.3 micrograms/lb) of
      body weight, i.v. RESULTS: Baseline serum cortisol concentrations were similar at
      each sampling time. Compared with the effects of freshly reconstituted
      cosyntropin, administration of cosyntropin that had been frozen did not have a
      significantly different effect on serum cortisol concentrations. CLINICAL
      IMPLICATIONS: Cosyntropin can be reconstituted and stored frozen at -20 C in
      plastic syringes for 6 months with no adverse effects on bioactivity of the
      polypeptide.

PMID- 9604026
TI  - Effect of time of sample collection on serum thyroid-stimulating hormone
      concentrations in euthyroid and hypothyroid dogs.
AB  - OBJECTIVE: To determine effect of time of sample collection on serum thyrotropin
      (canine thyroid-stimulating hormone [cTSH]) concentrations in euthyroid and
      hypothyroid dogs. DESIGN: Prospective study. ANIMALS: 6 healthy adult euthyroid
      dogs, 6 adult Beagles with 131iodine-induced hypothyroidism before and during
      administration of levothyroxine sodium, and 6 adult dogs with naturally
      developing hypothyroidism. PROCEDURE: Healthy euthyroid dogs were identified.
      Hypothyroidism was induced by administration of 131sodium iodide and confirmed by
      thyroid-stimulating hormone testing. These dogs then received levothyroxine for
      30 days. Naturally developing hypothyroidism was diagnosed on the basis of
      clinical signs, low serum thyroxine (T4) concentrations, and high cTSH
      concentrations or abnormal results on a thyrotropin-releasing hormone response
      test. Samples for measurement of cTSH and T4 concentrations were obtained at 2
      hour intervals from 8 AM to 8 PM. RESULTS: Mean (+/- SD) serum cTSH
      concentrations for healthy dogs, dogs with induced hypothyroidism before and
      during treatment, and dogs with naturally developing hypothyroidism were 0.11 +/-
      0.08, 3.31 +/- 1.30, 0.08 +/- 0.07, and 0.55 +/- 0.27 ng/ml, respectively.
      Diurnal variation in cTSH concentrations was not detected. Clinically important
      random fluctuations in cTSH concentrations were detected for dogs with naturally
      developing hypothyroidism. CLINICAL IMPLICATIONS: Sample collection time does not
      appear to predictably influence cTSH concentrations; however, dogs with naturally
      developing hypothyroidism may have random fluctuations in cTSH concentrations.

PMID- 9604027
TI  - Owner experiences with home use of a gastrostomy tube in their dog or cat.
AB  - OBJECTIVE: To describe owner experiences with gastrostomy tubes used at home.
      DESIGN: Telephone survey. ANIMALS: 20 cats and 5 dogs. PROCEDURE: Owner's
      opinions obtained by phone interview. RESULTS: Although 32% (8/25) of owners were
      initially reluctant to feed their cat or dog through the gastrostomy tube, 92%
      (22/24) of owners became comfortable with the procedure. Eighty-four percent
      (21/25) of owners were able to feed their dog or cat unassisted; 16% (4/25)
      required another person to help. Median time required for feeding was 19.8
      minutes. Ninety-six percent (24/25) of owners believed their dog or cat was
      comfortable with the procedure. Eighty-four percent (21/25) of owners experienced
      complications or difficulties. Most problems involved bandage maintenance,
      administration of food through the syringe and tube, or acquisition of syringes
      and special foods. Ninety-six percent (22/23) of owners would be willing to use a
      gastrostomy tube again. CLINICAL IMPLICATIONS: Most owners had positive
      experiences with the feeding experience and would be willing to use gastrostomy
      tube feeding again. Difficulties encountered by owners were not serious and could
      be avoided by specific client instruction.

PMID- 9604028
TI  - Extramedullary plasmacytoma in the trachea of a dog.
AB  - A 10-year-old spayed female mixed-breed dog was examined because of acute
      inspiratory dyspnea. Radiography and tracheoscopy revealed a discrete, solitary
      mass originating from the membranous portion of the trachea at the level of the
      thoracic inlet. Tracheal resection and anastomosis were performed, and on
      histologic examination of the resected tissue, extramedullary plasmacytoma was
      diagnosed. Although tracheal tumors are rare in dogs, they should be considered
      during evaluation of dogs with signs of airway obstruction. Prognosis is
      excellent for dogs with extramedullary plasmacytoma in which surgical excision is
      complete.

PMID- 9604029
TI  - Association between long periods without high-speed workouts and risk of complete
      humeral or pelvic fracture in thoroughbred racehorses: 54 cases (1991-1994).
AB  - OBJECTIVE: To determine whether a two-month or longer period without official
      high-speed workouts (lay-up) is associated with humeral or pelvic fracture in
      Thoroughbred racehorses. DESIGN: Reprospective study. ANIMALS: Thoroughbred
      racehorses in California that were euthanatized because of a complete humeral or
      pelvic fracture. PROCEDURE: Age, sex, activity, number of lay-ups, number of days
      from a race or official timed workout to fracture, number of days from end of
      last lay-up to fracture, mean duration of lay-ups, and total number of days in
      race training were compared between horses with humeral fractures and horses with
      pelvic fractures. A case-crossover study was used to estimate relative risk for
      fracture of the humerus or pelvis occurring within hazard periods of 10 and 21
      days following lay-up, compared with periods following more regular participation
      in official racing or timed workout events. RESULTS: Horses with pelvic fractures
      were more often female, older, and had 0 or > or = 2 lay-ups. Horses with humeral
      fractures were typically 3-year-old males that had 1 lay-up. Horses with pelvic
      fractures had more total days in race training, fewer days from last exercise
      event to fracture, and a greater number of days from end of last lay-up to
      fracture than horses with humeral fractures. Return from lay-up was strongly
      associated with risk for humeral fracture during hazard periods of 10 and 21 days
      (relative risk = 71 and 45, respectively). CLINICAL IMPLICATIONS: Risk of humeral
      fracture may be reduced if horses are cautiously reintroduced into race training
      after lay-up.

PMID- 9604030
TI  - Dietary control of exertional rhabdomyolysis in horses.
AB  - OBJECTIVE: To determine whether feeding a low-carbohydrate, high-fat diet would
      decrease severity of exercise-induced muscle injury in horses with exertional
      rhabdomyolysis. ANIMALS: 19 horses with a history of exertional rhabdomyolysis.
      DESIGN: Case series. PROCEDURE: Specimens of the semitendinosus or
      semimembranosus muscle were obtained for histologic examination, and serum
      creatine kinase (CK) and aspartate transaminase (AST) activities 4 hours after
      exercise were determined. Horses were then fed a low-carbohydrate, high-fat diet,
      and serum CK and AST activities 4 hours after exercise were reevaluated at
      approximately monthly intervals for 3 to 6 months. RESULTS: Serum CK and AST
      activities 4 hours after exercise were high before any change in diet. All 19
      horses had evidence of chronic myopathic change and abnormal glycogen
      accumulation in muscle biopsy specimens; 11 horses also had evidence of complex
      polysaccharide accumulation. Adaptation to diet change required approximately 3
      to 6 months. Sixteen horses did not have any episodes of exertional
      rhabdomyolysis after 3 to 6 months of diet change, and 3 horses had mild episodes
      of exertional rhabdomyolysis following either a reduction in dietary fat intake
      or restriction in exercise. Postexercise serum CK and AST activities 3 to 6
      months after the change in diet were significantly less than initial values.
      CLINICAL IMPLICATIONS: Results indicated that exertional rhabdomyolysis may be a
      result of abnormal carbohydrate metabolism in some horses. Feeding a diet with
      low carbohydrate and high fat content may reduce severity of exercise-induced
      injury in some horses with exertional rhabdomyolysis.

PMID- 9604031
TI  - Adrenal insufficiency in a neonatal foal.
AB  - A 3-day-old female Pinto was admitted with profuse watery diarrhea and severe
      hypovolemic shock. After 1 week of intensive care, the foal developed seizures
      associated with profound serum electrolyte abnormalities suggestive of
      hypoadrenocorticism. Treatment with prednisone and isotonic saline (0.9% NaCl)
      solution led to prompt clinical response. Premature withdrawal of prednisone
      resulted in relapse of clinical signs. A diagnosis of adrenal insufficiency was
      made on the basis of clinical signs, electrolyte abnormalities, low baseline
      cortisol concentration, and lack of response to administration of exogenous
      adrenocorticotropin. Two months later, adrenocortical function was normal and the
      foal was doing well clinically. Clinical signs of acute adrenal insufficiency in
      neonatal foals can be confused with other conditions, such as septicemia,
      enteritis, and ruptured urinary bladder. A persistently low serum sodium-to
      potassium ratio associated with CNS malfunction should warrant investigation of
      adrenal gland function. Acute hypoadrenocorticism in foals may be reversible.

PMID- 9604032
TI  - Type-II renal tubular acidosis and ventricular tachycardia in a horse.
AB  - A 14-year-old Arabian mare was admitted for lethargy, anorexia, and low fecal
      output. On the basis of laboratory, physical examination, and
      electrocardiographic findings, diagnoses of type-II renal tubular acidosis (RTA),
      impaction of the large colon, and ventricular tachycardia were made. Diagnosis of
      type-II RTA was based on measurement of a low fractional excretion value for
      potassium and fractional excretion value for sodium within the reference range.
      In contrast, horses with type-I RTA have high fractional excretion values for
      sodium and fractional excretion values for potassium within reference ranges.
      Treatment consisted of intravenous and oral administration of sodium bicarbonate,
      intravenous administration of fluids, and oral administration of mineral oil and
      docusate sodium. Acidosis improved, and ventricular tachycardia resolved with
      resolution of acidosis. Oral administration of bicarbonate was continued after
      discharge. The mare had several relapses, which were associated with anorexia and
      low intake of supplemental bicarbonate. The mare was found dead 2 months after
      discharge.

PMID- 9604033
TI  - Pulsed dye laser lithotripsy for treatment of urolithiasis in two geldings.
AB  - Transendoscopic pulsed dye laser lithotripsy was effective in the treatment of
      calcium carbonate urothlithiasis in 2 adult geldings. Perineal urethrotomy
      provided convenient access for standing transendoscopic lithotripsy and
      evacuation of a large cystic calculus in one gelding. In the second horse, an
      obstructive urethral calculus was fragmented and removed by a transurethroscopic
      approach. Pulsed dye laser lithotriptor is effective in fragmentation of the most
      common form (calcium carbonate) of uroliths in horses and may be performed in
      standing horses with reduced surgical invasiveness and trauma to the urinary
      tract, compared with conventional approaches. The principle disadvantages include
      cost of the procedure, which is comparable to laparocystotomy, and the time delay
      required to make arrangements for use of the pulsed dye laser lithotriptor.

PMID- 9604034
TI  - Higher prevalence of mental disorders in socioeconomically deprived urban areas
      in The Netherlands: community or personal disadvantage?
AB  - OBJECTIVE: Major mental disorders occur more frequently in deprived urban areas.
      This study examines whether this occurs for all mental disorders, including less
      serious ones. It further assesses whether such a concentration can be explained
      by the socioeconomic status (SES) of the residents concerned or that a cumulation
      of problems in deprived areas reinforces their occurrence. DESIGN: Mental
      disorders were assessed by means of the General Health Questionnaire (GHQ) among
      4892 residents. Additional data were obtained on area deprivation, and on
      individual SES. Multilevel logistic regression models were used to take the
      hierarchical structure of the data into account, residents being nested in
      boroughs. SETTING: General population of the city of Amsterdam, the Netherlands.
      MAIN OUTCOME MEASURE: Prevalence of an increased (> or = 2) score on the GHQ, 12
      item version. RESULTS: Mental disorders occur more frequently in deprived areas
      but this can be explained by the lower SES of the residents concerned.
      CONCLUSIONS: The cumulation of mental disorders in deprived urban areas is mainly
      a result of a concentration of low SES people in these areas. Contextual factors
      of deprived urban areas give hardly any additional risk above that resulting from
      a low individual SES.

PMID- 9604035
TI  - Material standard of living, social class, and the prevalence of the common
      mental disorders in Great Britain.
AB  - STUDY OBJECTIVE: To test the hypothesis that poor material standard of living is
      independently associated with the prevalence of the common mental disorders after
      adjusting for occupational social class, and to estimate the population impact of
      poor material standard of living on the prevalence of these disorders. DESIGN:
      Cross sectional survey. Prevalence of the common mental disorders was assessed
      using the General Health Questionnaire, a self administered measure of
      psychiatric morbidity. PARTICIPANTS: 9064 adults aged 16-75 living in private
      households in England, Wales, and Scotland. MAIN RESULTS: The common mental
      disorders were significantly associated with poor material standard of living,
      including low household income (OR 1.24, 95% CI 1.00, 1.54) and not saving from
      income (OR 1.29, 95% CI 1.15, 1.45), after adjusting for occupational social
      class and other potential confounders. An independent association was also found
      with occupational social class of the head of household among women, but not men,
      after adjusting for material standard of living. The adjusted population
      attributable fraction for poor material standard of living (using a five item
      index) was 24.0%. CONCLUSIONS: Like mortality and physical morbidity, common
      mental disorders are associated with a poor material standard of living,
      independent of occupational social class. These findings support the view that
      recent widening of inequalities in material standards of living in the United
      Kingdom pose a substantial threat to health.

PMID- 9604036
TI  - Role of childhood health in the explanation of socioeconomic inequalities in
      early adult health.
AB  - STUDY OBJECTIVE: To examine the contribution of childhood health to the
      explanation of socioeconomic inequalities in health in early adult life. DESIGN:
      Retrospective data were used, which were obtained from a postal survey in the
      baseline of a prospective cohort study (the Longitudinal Study on Socio-Economic
      Health Differences in the Netherlands). Adult socioeconomic status was indicated
      by educational level, while health was indicated by perceived general health.
      Childhood health was measured by self reported periods of severe disease in
      childhood. Relations were analysed using logistic regression models. The
      reduction in odds ratios of "less than good" perceived general health for
      different educational groups after adjustment for childhood health was used to
      estimate the contribution of childhood health. SETTING: The population of the
      city of Eindhoven and surroundings in the south east of the Netherlands in 1991.
      PARTICIPANTS: 2511 respondents, aged 25-34 years, men and women, of Dutch
      nationality, were included in the analysis. MAIN RESULTS: There was a clear
      association between childhood health and adult health, as well as an association
      between childhood health and adult socioeconomic status. Approximately 5% to 10%
      of the increased risk of the lower socioeconomic groups of having a "less than
      good" perceived general health can be explained by childhood health. CONCLUSIONS:
      Childhood health contributes to the explanation of socioeconomic inequalities in
      early adult health. Although this contribution is not very large, it cannot be
      ignored and has to be interpreted largely in terms of selection on health.

PMID- 9604037
TI  - Role of body mass index in the prediction of all cause mortality in over 62,000
      men and women. The Italian RIFLE Pooling Project. Risk Factor and Life
      Expectancy.
AB  - STUDY OBJECTIVE: To evaluate the relation of body mass index (BMI) to short-term
      mortality in a large Italian population sample. DESIGN: Within the Italian RIFLE
      pooling project, BMI was measured in 47 population samples made of 32,741 men and
      30,305 women ages 20-69 years (young 20-44, mature 45-69). Data on mortality were
      collected for the next six years. MAIN OUTCOME MEASURES: Age adjusted death rates
      in quintile classes of BMI and Cox proportional hazards models with six year all
      causes mortality as end point, BMI as covariate and age, smoking, systolic blood
      pressure as possible confounders were computed. Multivariate analysis was tested
      in all subjects and after the exclusion of smokers, early (first two years)
      deaths, and both categories. RESULTS: The univariate analysis failed to
      demonstrate in all cases a U or inverse J shaped relation. The Cox coefficients
      for the linear and quadratic terms of BMI proved significant for both young and
      mature women. The minimum of the curve was located at 27.0 (24.0, 30.0, 95%
      confidence limits, CL) and 31.8 (25.5, 38.2, 95% CL) units of BMI, for young and
      mature women respectively. Similar findings were obtained even when exclusion
      were performed. No relation was found for young men while for mature adult men
      only the model for all subjects retained significant curvilinear relation
      (minimum 29.3; 22.4, 36.2, 95% CL). CONCLUSION: These uncommon high values of BMI
      carrying the minimum risk of death seems to be in contrast with weight
      guidelines. A confirmation of these findings in other population groups might
      induce the consideration of changes in the suggested healthy values of BMI.

PMID- 9604038
TI  - Weather temperatures and sudden infant death syndrome: a regional study over 22
      years in New Zealand.
AB  - STUDY OBJECTIVE: To examine and identify relationships between the sudden infant
      death syndrome (SIDS) and environmental temperature in Canterbury, New Zealand.
      DESIGN: A retrospective epidemiological study combining details of regional
      hourly temperature and reported SIDS cases. SETTING: Canterbury, New Zealand,
      between 1968 and 1989 inclusively. PARTICIPANTS: All infants reported as dying
      from SIDS within the Canterbury region. MAIN RESULTS: The SIDS incidence
      increased after months with prolonged colder minimum temperatures, confirming the
      seasonality of SIDS. After adjusting for this seasonality, days that showed
      little change in hourly temperature and days with warmer minimum temperatures
      recorded were seen to have a significantly increased the incidence of SIDS. No
      evidence was found for other relationships between the SIDS incidence and various
      measures of daily temperatures on the day of death, over the preceding eight days
      or between these days. Infants aged 12 weeks and over were more susceptible to
      SIDS on days when small hourly temperature changes were recorded than their
      younger counterparts; no other age differences emerged. CONCLUSIONS: This study
      confirmed that the incidence of SIDS is affected by seasonality and temperature
      on the day of death. In particular, after a prolonged period of cold minimum
      temperatures, infants were most at risk from SIDS on days on which either a
      warmer minimum temperature or little hourly variation in temperature were
      recorded. No other daily or lagged daily temperature factor (lagged up to eight
      days before the day of death) was statistically associated with the SIDS
      incidence. It is suspected that the inconsistent previously published lag effect
      findings actually describe some other phenomenon such as parental behaviour or
      infant thermoregulation.

PMID- 9604039
TI  - Impaired mobility and impaired working capacity among foreign born people and
      native born Swedes.
AB  - OBJECTIVE: The aim of this study is to analyse the influence of country of birth
      and attained level of education, on impaired mobility and impaired working
      capacity adjusted for age, sex, and other background variables. SETTING: Sweden.
      DESIGN: A random sample of 5798 men and 6072 women ages 55-74 years were
      interviewed face to face by Statistics Sweden 1986-1993. Dependent variable:
      impaired mobility and impaired working capacity. INDEPENDENT VARIABLES: sex, age,
      country of birth (Swedes, Finns, Western countries, south Europeans, and all
      others), attained level of education, marital status, form of tenure, and social
      network. This study was designed as a cross sectional study. The data were
      analysed with unconditional logistic regression in main effect models. The
      results are shown as odds ratios (OR) with 95% confidence intervals (CI).
      RESULTS: In general, poor health, defined as impaired working capacity or
      impaired mobility, proved to be more frequent among foreign born people and in
      all socially disadvantaged groups such as those with a low educational status,
      people renting a dwelling or with a poor social network. Impaired working
      capacity and impaired mobility were more frequent among female "all others". The
      impaired mobility among men and women born in south Europe was high with OR =
      2.65 (CI = 1.34, 5.25) and OR = 3.17 (CI = 1.44, 7.00) in the full model. Men and
      women from Finland and all other countries had high risks for impaired mobility
      when adjusted for all background variables. Finnish men and south European women
      had the highest odds ratios for impaired working capacity. There was a clear
      gradient between educational status and impaired working capacity, with the
      highest odds ratios for men and women, 2.39 and 1.92, with a low attained level
      of education, when adjusting for the independent variables. CONCLUSION: Country
      of birth and educational status are two important independent factors with
      influence on poor health defined as impaired mobility and impaired working
      capacity in age 55-74.

PMID- 9604040
TI  - Is forced dextrality an explanation for the fall in the prevalence of
      sinistrality with age? A study in northern England.
AB  - OBJECTIVES: The fall in the prevalence of left handedness with age has been
      attributed to either premature mortality or a cohort effect of forced dextrality.
      Evidence for forced dextrality was sought to differentiate between these
      competing theories. DESIGN: 6097 Edinburgh handedness inventories were used to
      calculate laterality quotients (LQ) with and without the questions relating to
      writing and drawing. These questions might be expected to be most influenced by
      forced dextrality. SETTING: The study was performed in a small industrial town in
      Lancashire, UK. PARTICIPANTS: Using the British family practitioner service where
      over 95% of the population are registered with a general practitioner a response
      rate of 82.17% was obtained with respect to the Edinburgh Inventory. RESULTS:
      Questions about writing and drawing on the Edinburgh Inventory contributed to the
      positivity (right handedness) of the mean LQ, but equally across the ages. When a
      negative LQ was used to define left handedness the prevalence of left handedness
      fell from 11.2% at age 15 to 4.4% at age 70. Removal of the questions about
      writing and drawing caused the prevalence of left handedness to fall from 10.5%
      at age 15 to 4.95% at age 70. CONCLUSIONS: Less than 20% of the fall in the
      prevalence of left handedness was accounted for by questions relating to writing
      and drawing. The fall in the prevalence of sinistrals in older age groups is not
      adequately explained by cohort effects of forced dextrality on the writing hand.

PMID- 9604041
TI  - Impact of diabetic retinopathy screening on a British district population: case
      detection and blindness prevention in an evidence-based model.
AB  - OBJECTIVES: To quantify case detection and blindness prevention attainable
      through screening for diabetic retinopathy in a district population. DESIGN:
      Literature review including a pooled estimate of screening test sensitivity, and
      quantitative modelling, including sensitivity analyses. SETTING AND PATIENTS: The
      diabetic population of a typical district health authority or health board. MAIN
      RESULTS: Evidence suggests that in a British general practice based diabetic
      population, prevalence of retinopathy requiring treatment would be between 1% and
      6%; annual incidence of blindness among diabetics with retinopathy requiring
      treatment would be between 6% and 9%; sensitivity of screening tests in detecting
      retinopathy requiring treatment would be between 50% and 88%; and treatment could
      prevent 77% of expected cases of blindness. Of those screened, about 4% would be
      correctly detected as requiring treatment during an initial screening round, but
      this yield could decrease to about 1% in subsequent annual screening rounds. Of
      those treated, about 6% would be prevented from going blind within a year of
      treatment and 34% within 10 years of treatment. CONCLUSIONS: Screening and early
      treatment of diabetic retinopathy can prevent substantial disability. The
      effectiveness and efficiency of screening could be enhanced by improving the
      performance of current tests or increasing use of mydriatic retinal photography,
      and by increasing uptake, particularly among diabetics at greatest risk.

PMID- 9604042
TI  - Economic burden of environmental tobacco smoke on Hong Kong families: scale and
      impact.
AB  - STUDY OBJECTIVE: To examine the financial cost of doctor consultations for cough,
      phlegm, and wheeze in children living in a home where family members smoke
      compared with those not exposed to environmental tobacco smoke. To model these
      costs to provide the Territory of Hong Kong with estimates of potentially
      avoidable health care resource use. DESIGN: Cross sectional questionnaire survey.
      SUBJECTS AND SETTING: All children (10,615) in classes primary 3 to 6 (aged 8-13
      years) attending 27 schools in two districts of Hong Kong in 1992 and their
      parents. MEASUREMENTS AND MAIN RESULTS: Doctor consultations during the previous
      three months for symptoms of either cough, phlegm or wheeze were higher in
      younger children, ranging from 22.9% in 8 year olds to 8.4% in those aged 12 or
      over. For those children living in homes with one, or more than one, smoker
      category (there were four categories of smokers: father, mother, siblings,
      others), the adjusted odds ratios (95% confidence intervals) for a doctor
      consultation for any of these symptoms were 1.15 (1.01, 1.31) and 1.38 (1.14,
      1.67) respectively. Using US$15 as the minimum cost incurred per consultation,
      the expected direct cost per annum per child of doctor consultations was 14%
      higher for children living in a one smoker category home and 25% for two or more
      compared with exposure to no smokers in the home. Using these values on a
      territory wide basis, the annual avoidable direct cost associated with exposure
      to tobacco smoke in children from birth to 12 years of age ranged from US$338,042
      to US$991,591. CONCLUSIONS: Exposure to environmental tobacco smoke not only
      provides a respiratory health risk for children but also an avoidable excess cost
      to the family's financial resources and health service providers.

PMID- 9604043
TI  - Effect of varying the time frame for COOP-WONCA functional health status charts:
      a nested randomised controlled trial in Bristol, UK.
AB  - STUDY OBJECTIVES: To investigate whether changing the stated time frame for COOP
      WONCA charts has any effect on responses. Specifically, to assess the effect of
      attempting to avoid the situation where the time frame crosses the onset of an
      acute episode. DESIGN: A randomised controlled trial of two time frames, nested
      within a main trial comparing early discharge with a hospital at home scheme
      against routine discharge policy. The time frames compared were the standard two
      weeks (four for the pain chart) and a shorter period of 48 hours for all seven
      charts. SETTING: Acute hospital wards in Frenchay Healthcare Trust and the Avon
      Orthopaedic Centre in Bristol. PARTICIPANTS: Patients entered into the main
      trial, who were medically stable, in need of continued rehabilitative care but
      suitable for discharge to hospital at home. MAIN RESULTS: A total of 200 patients
      were randomised, 106 to the shorter time frame, 94 to the standard charts. No
      clear differences were observed between the two groups for the proportion failing
      to self complete the charts. For the (seven) chart scores, only pain was
      statistically significantly different between the time frames (Mann-Whitney p =
      0.0085; proportion reporting moderate or severe pain 19% higher in the standard
      group, 95% confidence intervals 5% to 33%). For both this chart and that for
      change in health, however, there was evidence of greater differences between the
      versions of the chart among those admitted more recently (p values for relevant
      interactions 0.004 and < or = 0.001 respectively). CONCLUSIONS: While the present
      findings give some support for the wide applicability of the standard version,
      there is sufficient evidence here to indicate that the time frame may influence
      the results, particularly for patients with a recent acute episode. In the
      absence of further data, then, it would seem prudent to consider a shorter time
      frame for such patients, especially if the aim is to assess current health status
      or to measure changes over a comparatively short period of time, or both.

PMID- 9604044
TI  - Validity and accuracy of interview and diary data on children's medical
      utilisation in The Netherlands.
AB  - STUDY OBJECTIVE: To assess the validity and accuracy of children's medical
      utilisation estimates from a health interview and diary and the possible
      consequences for morbidity estimates. The influence of recall bias and respondent
      characteristics on the reporting levels was also investigated. DESIGN: Validity
      study, with the medical record of the general practitioner (GP) as gold standard.
      In a health interview and three week diary estimates of medical utilisation of
      children were asked and compared with a GP's medical record. SETTING: General
      community and primary care centre in the Netherlands. PARTICIPANTS: Parents of
      1,805 children and 161 GPs. MAIN RESULTS: The sensitivity of the interview (0.84)
      is higher than the diary (0.72), while specificity and kappa are higher in the
      diary (0.96; 0.64) than in the interview (0.91; 0.5-8). Recall bias, expressed as
      telescoping and heaping, is present in the interview data. Prevalence estimates
      of all morbidity are much higher in the interview, except for skin problems.
      Compared with a parental diary more consultations are reported exclusively by the
      GP for children from ethnic minorities (OR 1.6), jobless (OR 2.3), and less
      educated mothers (OR 2.6). CONCLUSIONS: Estimates of medical utilisation rates of
      children are critically influenced by the method of data collection used.
      Interviews are prone to introduce recall bias, while diaries should only be used
      in populations with an adequate level of literacy. It is recommended that medical
      records are used, as they produce most consistent estimates.

PMID- 9604045
TI  - Physical activity and predisposition for hip fractures: a review.
AB  - Studies on the association between physical activity and hip fractures are
      reviewed. All the studies, which comprise four follow-up studies, one nested case
      control study and 17 case-control studies, suggest a protective effect of
      physical activity with regard to hip fractures. The association is strong and
      consistent with physical activity in leisure, weaker with respect to physical
      activity at work. The association is present for physical activity from childhood
      to adult age, and it is consistent in study populations from the USA, Australia,
      Asia and Northern and Southern Europe, in spite of very different hip fractures
      incidences in these populations. The magnitude of the association is difficult to
      assess because of varying criteria for exposure, but to be among the physically
      active seems to reduce the risk of later hip fracture by up to 50%. It seems that
      even daily chores, such as climbing stairs and walking, protect against hip
      fracture.

PMID- 9604047
TI  - Asynchrony between the rates of standing height gain and bone mass accumulation
      during puberty.
AB  - During puberty, the marked increased in both standing height and bone mass appear
      to be dissociated in time, the former occurring earlier than the latter. However,
      the age or pubertal stage at which this dissociation is maximal in girls as
      opposed to boys, and whether this dissociation is similar at all parts of the
      skeleton, are not clearly established. Standing height and bone mineral mass, as
      assessed by measuring areal bone mineral density (BMD), at the levels of the
      lumbar spine, femoral neck and midfemoral shaft, were measured in 98 females and
      100 males between the ages of 9 and 19 years twice at a 1-year interval. In
      males, the greatest difference between height and BMD gains occurred in the 13-14
      year age group and was more pronounced for the lumbar spine and femoral neck than
      for the midfemoral shaft. In females, the greatest difference was detectable at a
      younger age (11-12 year age group) and appeared to be of a lower magnitude than
      in males. In both genders, the maximal difference occurred during the period of
      peak height velocity, which corresponded to the pubertal stages P2-P3. Such a
      dissociation between the rates of statural growth and mineral mass accrual could
      define a state of relatively low bone mass and contribute to the higher incidence
      of fracture known to occur at the age and/or pubertal stage when this
      dissociation is maximal.

PMID- 9604046
TI  - Demonstration of cellular aging and senescence in serially passaged long-term
      cultures of human trabecular osteoblasts.
AB  - The proliferative capacity and cellular and biochemical characteristics of human
      trabecular bone osteoblasts were analysed throughout their replicative lifespan
      in vitro. Like several other cell types, human osteoblasts demonstrated a typical
      Hayflick phenomenon of cellular aging comprising a period of rapid proliferation
      until cumulative population doubling level (CPDL) 22 to 24, followed by a phase
      of slow growth and the final cessation of cell division at CPDL 32 to 34.
      Comparing young cells (less than 20% lifespan completed) and old cells (more than
      90% lifespan completed) revealed a progressive increase in population doubling
      (PD) time, a decrease in attachment frequency, a decrease in the number of S
      phase positive cells, a decrease in the rates of DNA, RNA and protein synthesis,
      an increase in the protein content per cell and an increased proportion of
      senescence-specific beta-galactosidase positive cells. While osteoblastic
      production of collagen type I decreased progressively during aging, alkaline
      phosphatase activity dropped rapidly after the first few passages and then
      remained constant during the rest of the proliferative lifespan, Significant
      morphological changes from thin and spindle-shaped early passage young cells to
      large, flattened and irregularly shaped late passage old cells full of
      intracellular debris were observed. In comparison, osteoblasts established from
      an osteoporotic bone sample showed a maximum CPDL of less than 5, had a longer PD
      time and exhibited abnormal senescent morphology. Thus, we have demonstrated for
      the first time that human osteoblasts, like several other diploid cell types,
      have a limited proliferative capacity in vitro and undergo aging and senescence
      as measured by various cellular and biochemical markers. In addition, preliminary
      studies show that cells from osteoporotic bone have a severely reduced
      proliferative capacity. This model of bone cell aging facilitates study of the
      molecular mechanisms of osteoblast senescence as well as factors related to
      osteoblast dysfunction in patients with osteoporosis.

PMID- 9604048
TI  - Associations of vitamin C, calcium and protein with bone mass in postmenopausal
      Mexican American women.
AB  - We investigated the associations of vitamin C, calcium and protein intakes with
      bone mass at the femoral neck and lumbar spine in postmenopausal Mexican American
      women. Bone mass was measured by dual-energy X-ray absorptiometry (DXA) and
      expressed as areal (BMD, g/cm2) and volumetric (bone mineral apparent density or
      BMAD, g/cm3) bone mineral density. Diet was assessed using a modified version of
      the National Cancer Institute Food Questionnaire, which was administered by
      trained bilingual interviewers familiar with Mexican dietary practices. Data
      gathered from 125 subjects were analyzed using multiple linear regression
      analysis with age, body mass index (BMI), acculturation, years of estrogen use,
      physical activity, total energy intake, and the nutrient of interest as
      independent variables. Neither calcium nor calcium/protein ratio was associated
      with bone mineral density. There was evidence of a positive association between
      dietary vitamin C intake and femoral neck BMD (beta = 0.0002 g/cm2 per mg/day, SE
      = 0.00006, p < 0.05), but vitamin C was not associated with lumbar spine bone
      mass. Further investigation of the role of vitamin C in skeletal health is
      warranted.

PMID- 9604049
TI  - Ovariectomy in the rat induces a rapid increase in the urinary excretion of
      hydroxylysine glycosides and non-reducible crosslink residues.
AB  - The ovariectomized rat is the most commonly used animal model of human
      postmenopausal osteoporosis, exhibiting a high rate of bone turnover with
      resorption exceeding formation. At present, bone turnover is quantified directly
      by dynamic histomorphometry. The aim of the present study was to determine
      whether the measurement of the urinary output of some specific bone collagen
      catabolites--pyridinolines and hydroxylysine glycosides--could be used to
      indirectly monitor the initial phase of bone turnover increase in ovariectomized
      90-day-old rats. Ninety-day-old female rats were randomly divided into three
      groups (n = 6): ovariectomized, sham-operated and non-treated controls. Urine
      samples (24 h) were collected 6 days before surgery and twice weekly for the 4
      weeks following ovariectomy. Urinary excretion of pyridinoline (PYD),
      deoxypyridinoline (DPD), glucosyl-galactosyl-hydroxylysine (GGHYL) and galactosyl
      hydroxylysine (GHYL) were measured. As expected, ovariectomy was associated with
      a significant decrease in bone mineral density in both the proximal tibial and
      distal femoral metaphysis. Compared with both sham-operated and control animals,
      ovariectomized rats showed significant increases in PYD, GGHYL, and GHYL urinary
      output 8 days after surgery and in DPD output after 15 days. These changes were
      maintained throughout the study. The results confirm that measurement of the
      urinary excretion of pyridinolines and hydroxylysine glycosides represents a
      powerful tool for detecting the onset of bone turnover in ovariectomized 90-day
      old rats.

PMID- 9604051
TI  - Three-year longitudinal study with quantitative ultrasound at the hand phalanx in
      a female population.
AB  - A longitudinal study was conducted to assess the value of quantitative ultrasound
      (QUS) measurement in predicting the risk of fracture and to evaluate how QUS
      parameters change with ageing and the climacteric. A group of 211 female subjects
      underwent assessment by QUS at the distal metaphysis of the first phalanx of the
      last four fingers of the hand on two occasions 3 years apart. The subjects were
      selected from outpatients attending the orthopaedic clinic, provided they were
      not affected by metabolic disease or under treatment with drugs known to
      interfere with bone metabolism. In vivo the coefficient of variation and the
      standardized coefficient of variation of the QUS device were respectively 0.5%
      and 3.5%. The correlation between the values of the amplitude-dependent speed of
      sound (AD-SoS) in the two measurements was r = 0.92. In 77.3% of the subjects
      during the observation period we recorded a reduction in AD-SoS. During the study
      22 fractures were observed in peripheral sites, 8 of which were associated with
      'low-energy trauma'. By multiple logistic regression analysis we found that the
      relative risk of fracture for a 1 SD reduction in AD-SoS was 1.5 (95% CI 1.1-1.7)
      (p < 0.03). The percentage of low-energy fractures significantly increased among
      those subjects with an AD-SoS value lower than 1850 m/s (T-score < -3.5) at the
      first examination (p <0.0001). QUS investigation proved to be especially
      sensitive to hormonal changes associated with the climacteric: we observed a mean
      decrease of 56 m/s in the AD-SoS for women who entered the menopause between the
      first and the second QUS test (average time since menopause 2 years), as against
      10 m/s in subjects remaining premenopausal. In a group of 146 subjects with
      'normal' Ad-SoS at the first examination, we observed a significant reduction in
      AD-SoS only after 40 years of age. This study demonstrates that measurement of
      the AD-SoS at the phalanx is reproducible, can be employed to assess the risk of
      fracture, and is able to detect age-related alterations in bone tissue.

PMID- 9604052
TI  - Is the metatarsal fracture in postmenopausal women an osteoporotic fracture? A
      cross-sectional study on 113 cases.
AB  - To evaluate whether metatarsal fracture in postmenopausal women can be related to
      osteoporosis, a sample of 113 postmenopausal women with metatarsal fracture due
      to minor trauma were recruited. Demographic and clinical data were compared with
      a control group of 339 healthy age-matched women and with a sample of 224 women
      with wrist fracture. In all women, bone mineral density (BMD) was measured at the
      lumbar spine by dual-energy X-ray absorptiometry. The average age of the
      metatarsal fracture group was slightly lower than that of the wrist fracture
      group (56.9 vs 58.4 years). Women with metatarsal and wrist fracture had a
      significantly higher age at menarche, lower age at menopause and lower body mass
      index when compared with controls. In both fracture groups BMD was significantly
      lower compared with controls. In stepwise logistic regression models, factors
      associated with metatarsal fracture risk were age at menopause (odds ratio [OR]
      0.86; 95% confidence interval [CI] 0.81-0.92) and BMD (OR per -1 SD 2.44; CI 1.92
      3.11). Factors associated with wrist fracture risk included age at menopause (OR
      0.89; CI 0.84-0.93) and BMD (OR per -1 SD 2.65; CI 2.17-3.24). The similarities
      existing in risk factors and their estimates between a well-recognized
      osteoporotic fracture such as wrist fracture and metatarsal fracture, support the
      hypothesis that the latter can be included among osteoporotic fractures.

PMID- 9604050
TI  - Longitudinal evaluation of a bone resorption marker in elderly subjects.
AB  - The variability over time in the excretion of a bone resorption metabolite
      (collagen type I N-telopeptide crosslink, NTx) was evaluated in a cohort of
      community-dwelling elderly men and women (mean age 73 years). Three annual 24-h
      urine samples were collected. NTx concentration was measured using an established
      ELISA. Total (24-h) NTx excretion as well as Ntx/creatinine concentration were
      compared. Men had a significantly lower excretion of NTx/creatinine than women
      who were not on hormone replacement therapy. Overall, the within-subject long
      term coefficient of variability for Ntx/creatinine was 26%. The correlation
      coefficient between the samples taken a year apart was higher for the 24-h NTx
      excretion (r = 0.66) than for the 24-h creatinine excretion (r = 0.51). The
      consistency of NTx excretion over time was also evaluated in all 93 subjects with
      three yearly samples using Kendall's rank correlation method; the resulting
      coefficient of concordance was 0.78 (significant at the 0.01 level). These
      results indicate that while NTx excretion varies in subject samples collected
      over a period of 2 years, this variability is not much greater than the daily
      variation reported for NTx and other bone metabolism markers. The relative
      reproducibility of NTx excretion over time in this age group was also evident in
      the coefficient of concordance. The results provide support for stratifying
      subjects according to level of bone resorption and identifying those subjects
      with high turnover who may be at greater risk of osteoporotic fracture.

PMID- 9604053
TI  - Effect of osteoarthritis in the lumbar spine and hip on bone mineral density and
      diagnosis of osteoporosis in elderly men and women.
AB  - To determine in the elderly the effect of osteoarthritis on bone mineral density
      (BMD) and on diagnosis of osteoporosis, lumbar spine and hip were radiographed
      and BMD measured by dual-energy X-ray absorptiometry (DXA) in 120 men and 314
      women, aged 60-99 years. Prevalence and severity of osteoarthritis were scored on
      osteophytes, joint space narrowing and bone sclerosis. Ultrasound measurements
      were also made at the heel to examine whether osteoarthritis at hip or lumbar
      spine influence bone at this remote site. Osteophytes were the commonest feature,
      with men having a higher prevalence than women, and lumbar spine having more
      disease than hip. Lumbar spine osteophytes affected 75% of men and 61.1% of
      women, and hip osteophytes affected 31.7% of men and 27.4% of women. Stepwise
      multiple regression analysis using age, weight, height, osteophytes, sclerosis
      and joint space narrowing indicated that lumbar osteophytes explained 16.6% of
      variation in lumbar spine BMD in women, and 22.4% in men. Hip osteophytes had a
      minimal effect on hip BMD, accounting for only 2.2% of variation in women, and
      none in men. Sclerosis and joint narrowing had little effect on BMD at lumbar
      spine or hip. Indirect effects of osteoarthritis on BMD were small and
      inconsistent across genders. Lumbar spine osteophytes in men explained 3.1% of
      hip BMD variation and 6% of variation in speed of sound at the heel, whereas hip
      osteophytes in women explained 2.2% of lumbar spine BMD variation. Osteoporosis
      at the hip, defined as BMD < 2.5 SD of the young normal mean, was present in
      33.1% of women and 25.8% of men, whereas, at the lumbar spine it was present in
      only 24.2% of women and 4.2% of men. However, in women and men free of spinal
      osteoarthritis, 37.7% of women and 10% of men had osteoporosis. We conclude that
      lumbar spine osteophytes affect most subjects over the age of 60 years, and
      contribute substantially to lumbar spine BMD measured in the anteroposterior
      position by DXA. The effect is largely direct by virtue of osteophytes being
      included in the BMD measurement. However, a small indirect effect on remote
      skeletal sites is also present. Diagnosis of osteoporosis and assessment of
      osteoporotic fracture risk in the elderly should be based on hip BMD and not on
      anteroposterior lumbar spine, unless spinal osteoarthritis has been excluded.

PMID- 9604054
TI  - Evaluation of the European Spine Phantom in a multi-centre clinical trial.
AB  - The European Spine Phantom (ESP) has recently been developed as a universal
      standard for instruments measuring bone density. The ESP is composed of three
      semi-anthropomorphic hydroxyapatite vertebrae of varying densities surrounded by
      soft tissue equivalent plastic designed to resemble human bone and soft tissue
      when scanned on bone densitometers. In multi-centre studies it is particularly
      important to verify that each participating bone densitometer is performing in a
      stable and linear fashion. The aim of this study was to evaluate the ESP within
      the context of a multi-centre clinical trial. Eighteen centres in the UK and
      Canada with dual-energy X-ray absorptiometry (DXA) instruments (Lunar DPX, DPX
      alpha and DPX-L) participated in the study. The ESP was scanned 10 times on each
      instrument without repositioning using standardized protocols. The precision of
      the bone mineral density (BMD) measurements (LI-3) expressed as a coefficient of
      variation ranged from 0.4% to 1.1% (mean 0.7%). The mean BMD of each instrument
      was expressed as a percentage difference from the overall mean and ranged from 
      1.33% to 1.33%. Linear regression analysis showed that all instruments behaved in
      a linear fashion across the range of densities with correlation coefficients all
      > or = 0.999 and standard errors of the estimate < 1.5% of the mean BMD ESP
      value. The data from this study demonstrate that the ESP is a useful phantom for
      assessing the linearity, stability and differences between DXA instruments from
      one manufacturer.

PMID- 9604055
TI  - Effect of sodium fluoride on the prevention of corticosteroid-induced
      osteoporosis.
AB  - To investigate whether sodium fluoride (NaF) is able to prevent bone loss in
      patients treated with corticosteroids (Cs), we performed a randomized double
      masked, placebo-controlled trial with 44 Cs-treated patients without established
      osteoporosis, defined as the absence of previous peripheral fractures and
      vertebral deformities on radiographs. The effects of NaF (25 mg twice daily) and
      placebo on the bone mineral density (BMD) of the lumbar spine and hips were
      compared at baseline and at 6, 12, 18 and 24 months. After 2 years, the BMD of
      the lumbar spine had decreased in the placebo group by 3.0% (95% CI: -4.9% to 
      1.0%; p < 0.01); in the NaF group there was a statistically insignificant
      increase in BMD of 2.2% (95% CI: -0.8% to +5.3%). The difference in the changes
      in BMD between the two groups was +5.2% (95% CI: +1.8% to +8.6%; p < 0.01). In
      the hips, BMD had decreased after 2 years in both groups: in the placebo group by
      -3.0% (95% CI: -5.0% to -1.0%; p < 0.05) and in the NaF group by 3.8% (95% CI: 
      6.1% to -1.5%; p < 0.01). The difference in the changes in BMD between the two
      groups was not significant: +0.8% (95% CI: -2.1% to +3.8%). Three vertebral
      deformities were observed in the placebo group and one in the NaF group
      (insignificant difference), while no peripheral fractures occurred during the
      study period. It is concluded that in Cs-treated patients without established
      osteoporosis NaF prevents bone loss in the lumbar spine but does not have a
      positive effect on the BMD of the hips.

PMID- 9604056
TI  - Implementation of an osteoporosis research program with a mobile dual-energy X
      ray absorptiometry unit: the Montana/Wyoming experience.
AB  - To expedite recruitment, and subject participation, for a large clinical
      osteoporosis therapy trial utilizing the bisphosphonate ibandronate, an
      integrated network of 13 satellite clinical sites was developed, linked by a
      mobile clinic vehicle transporting a dual-energy X-ray absorptiometry (DXA) unit.
      A predominantly rural area of the United States (Montana, northern Wyoming) was
      accessed for the project, due to the large pool of potential subjects living in
      this area who were not yet involved in osteoporosis clinical studies. The results
      of the project to date (through 10 months) confirm the feasibility of such a
      study design, with 1774 subjects screened by DXA for the study, and 280 (15.8%)
      accepted. The mobile DXA unit has functioned according to specifications for a
      stationary DXA machine, with the stability of spine phantom measurements over 10
      months assessed as a coefficient of variation of 0.46%. The success of the
      project validates the concept of performing clinical osteoporosis therapy trials
      in previously underutilized rural community settings, facilitated by a satellite
      site network and mobile clinic.

PMID- 9604057
TI  - Consensus development statement on osteoporosis.

PMID- 9604058
TI  - Doors of perception.

PMID- 9604059
TI  - Assimilation: central and peripheral effects.
AB  - Assimilation and contrast have opposite effects: Contrast leads to an increase of
      perceived differences between neighbouring fields, whereas assimilation leads to
      a reduction. It is relatively easy to demonstrate these effects, but the precise
      localisation of these effects in the perceptual system is not yet possible. In an
      experiment the strength of assimilation effects was modified by adding spatial
      noise. By varying the localisation in perceived space of the added noise (by
      presentation of the noise pattern with different binocular disparities) the
      masking effect of this noise can be influenced. Masking caused by binocularly
      disparate noise is less than masking caused by binocularly non-disparate noise.
      It is concluded that the effect at least partly occurs beyond the (binocular)
      locus of separation in different depth planes. A similar approach, involving
      moving noise, is also presented. Finally, several demonstrations show that images
      that are peripherally similar can give rise to differences in the perceived
      amount of assimilation. These effects further indicate that a central mechanism
      is involved in assimilation.

PMID- 9604060
TI  - Depth perception during diplopia is direct.
AB  - Although depth is experienced with targets at large disparities when they are
      seen as double or diplopic, whether that depth is as direct as with fused targets
      has been a matter of considerable uncertainty. Researchers have often claimed
      that judgments of the depth of diplopic targets during simple near/far tasks rely
      upon indirect associations with eye-muscle proprioception or a copy of the
      vergence drive signal. We designed a four-alternative task that could not be
      performed without a direct appreciation of depth. Observers judged the depths of
      each of two Gabor stereo pairs presented simultaneously. Disparities were always
      above each observer's measured diplopia threshold. The signs of the disparities
      were varied independently and observers reported the perceived depth near and far
      for each target. Our results demonstrate conclusively that depth during diplopia
      requires neither proprioception nor an efferent copy but is direct.

PMID- 9604061
TI  - The effect of depth rotation on object identification.
AB  - Five experiments are reported in which the time to verify the name of different
      three-dimensional common objects shown rotated in depth was investigated. Views
      of computer-generated images of elongated objects rotated in steps of 30 degrees
      along six axes of rotation were used as stimuli. A significant main effect of
      view was found in all experiments. This effect was initially attributed to the
      relatively slower verification times to the end-on views of objects but further
      analysis revealed that views 30 degrees off the end-on views were significantly
      slower to verify than other views. Objects with gravitational uprights yielded
      the same effects as objects without gravitational uprights. The results were not
      dependent on practice with the stimuli prior to the experiment or on repeated
      exposure of the views during the experiment. Also, there was no benefit found for
      the identification of shaded over silhouetted images of objects when shown in
      more-conventional views but unconventional views were more recognisable when
      shaded than when silhouetted. Last, initial verification times for familiar views
      of a set of novel objects were faster than for unfamiliar views even when the
      views were unconventional. With practice on unfamiliar views, however, the same
      function relating view to verification time found for familiar objects was found
      for the novel objects. The results suggest that for recognition purposes visual
      memory stores discrete views of objects but it characteristically favours a
      canonical range of views of elongated objects that are based on the salient
      geometry of the objects so that more unconventional or foreshortened views are
      less readily recognised.

PMID- 9604062
TI  - Global orientation disrupts the detection of a similar local orientation.
AB  - Two experiments were carried out with organised displays in order to examine the
      role of similarity between global and local orientation in visual search. In both
      experiments, distractors were organised to form a diagonal line of plus or minus
      45 degrees. In experiment 1, target displays were presented tachistoscopically.
      Participants searched for a target letter 'Q' among distractor letters 'O'. In
      experiment 2, participants performed a heterogeneity task with target line
      segments that could have an orientation of either plus or minus 45 degrees. The
      target appeared partly or completely inside a distractor circle. In both
      experiments, the target was more difficult to detect when the critical feature
      aligned with the slope of the global diagonal than when the feature did not
      align. Taken together, the two experiments suggested a sequential global-to-local
      processing in which the orientation of the global figure disrupts the detection
      of a similar local orientation.

PMID- 9604063
TI  - What represents a face? A computational approach for the integration of
      physiological and psychological data.
AB  - Empirical studies of face recognition suggest that faces might be stored in
      memory by means of a few canonical representations. The nature of these canonical
      representations is, however, unclear. Although psychological data show a three
      quarter-view advantage, physiological studies suggest profile and frontal views
      are stored in memory. A computational approach to reconcile these findings is
      proposed. The pattern of results obtained when different views, or combinations
      of views, are used as the internal representation of a two-stage identification
      network consisting of an autoassociative memory followed by a radial-basis
      function network are compared. Results show that (i) a frontal and a profile view
      are sufficient to reach the optimal network performance; and (ii) all the
      different representations produce a three-quarter view advantage, similar to that
      generally described for human subjects. These results indicate that although
      three-quarter views yield better recognition than other views, they need not be
      stored in memory to show this advantage.

PMID- 9604064
TI  - Face recognition with multi-tone and two-tone photographic negatives.
AB  - The effects of photographic negatives on face recognition are often studied in
      two different ways--faces are learned and tested in photographic negatives (NN)
      or the contrast is reversed between learning and testing, i.e. they are learned
      in positives and tested in negatives (PN) or vice versa (NP). We have examined
      recognition performance for faces under these three conditions along with a
      control condition where faces were learned and tested in positives (PP). Using
      multi-tone face images, we found that the effect of photographic negatives was
      more pronounced in PN and NP than in NN. No differences were found between PN and
      NP or between NN and PP. When two-tone face images were used, recognition
      performance was worse in all conditions, except PP, when compared to the multi
      tone counterparts. Our results show that contrast incongruency between learning
      and testing is the predominant factor affecting performance and that deficits in
      sensory coding or retention of negative face images are unlikely to be major
      factors. The advantage of multi-tone over two-tone negatives can be attributed to
      preserved facial information carried by the high-spatial-frequency components of
      the image.

PMID- 9604065
TI  - The psychophysics of J-R-L Delboeuf (1831-1896).
AB  - Delboeuf's writings on psychophysics are little known nowadays. The object of
      this paper is to describe the psychological contributions of this eminent Belgian
      psychologist of the second half of the 19th century. A true pioneer of
      experimental psychology, his work on psychophysics began in 1865 at the
      University of Gand (Ghent) but was not published until 1873 and following years.
      His work in this area is characterised on the one hand by the adoption of a
      logarithmic law relating sensation strength to stimulus strength, but which
      differed from that of Fechner; and on the other hand by the utilisation of a
      psychophysical technique based on brightness contrast (now called the 'bisection
      method'). Even though, Delboeuf was classified by Fechner in his later writings
      as an opponent of his beliefs. Delboeuf was nevertheless one of his least
      virulent critics and the only psychologist of that era to have adopted a
      logarithmic law. Delboeuf's work is not only of historic interest; his original
      ideas possess sufficient interest for present-day psychophysicists to reexamine
      them.

PMID- 9604066
TI  - Loss of a forest: perceptual fading and filling-in of static texture patterns.
AB  - Fading and filling-in of static texture patterns is demonstrated with the use of
      a matrix of Chinese characters with vertical or oblique line components. An
      asymmetric effect is demonstrated by exchanging foreground and background
      characters.

PMID- 9604067
TI  - The illusion of The Future.

PMID- 9604068
TI  - The rise of asthma and atopy.

PMID- 9604070
TI  - CMV infection is associated with transplant renal artery stenosis.
AB  - Transplant renal artery stenosis (TRAS) is a significant cause of graft
      dysfunction, with no clearly defined aetiology. Evidence suggests a role for
      cytomegalovirus (CMV) infection in cardiac transplant vasculopathy and in native
      coronary artery restenosis after angioplasty. We investigated the relationship
      between CMV infection after renal transplantation and subsequent development of
      TRAS. Of 917 patients receiving renal transplants at a single centre from 1978 to
      1994, 75 had TRAS diagnosed by angiography. Each was paired with a control
      transplanted patient with no TRAS, matched for age, sex, year of transplant and
      number of grafts. Incidence of CMV infection between transplantation and the time
      of diagnosis of TRAS was assessed in both groups, using clinical and serological
      criteria to assign patients to three groups: definite CMV infection (CMV-DEF),
      possible infection (CMV-POSS) and no evidence of infection (CMV-NUL). CMV-DEF was
      significantly more common in TRAS than in controls (36 vs. 12, respectively, p <
      0.001) and CMV-NUL was less common (TRAS 15, controls 33). We have previously
      reported an increased incidence of acute rejection in patients with TRAS. The
      subset of patients with no rejection episodes also had significantly more CMV-DEF
      cases in the TRAS group (54%) than in controls (10%) (p = 0.002). The data are
      consistent with the hypothesis that CMV infection can contribute to the
      development of TRAS. The relationship between CMV and TRAS did not arise from an
      excess of anti-rejection treatment in the TRAS group. CMV-induced large-vessel
      damage in immunosuppressed patients may occur through local infection and the
      mitogenic actions of viral gene products within cells of the vessel wall.

PMID- 9604069
TI  - Asthma and allergy--disorders of civilization?

PMID- 9604071
TI  - Hypoglycaemia on and after admission in Kenyan children with severe malaria.
AB  - We investigated the pathophysiology of hypoglycaemia in severe malaria in African
      children, especially the potential importance of glycerol as a substrate for
      gluconeogenesis, and whether substrate limitation contributes to hypoglycaemia in
      severe disease. Of 171 children with moderate or severe malaria, 16% were
      hypoglycaemic on admission, while at least 9% of children with severe malaria
      treated with quinine and a concurrent 4% dextrose infusion had a definite episode
      of hypoglycaemia after admission. Blood levels of gluconeogenic precursors are as
      high (alanine and lactate) or higher (glycerol) in those with either
      hypoglycaemia on or after admission as they are in children never having an
      episode of hypoglycaemia. Among children with severe malaria, however, those
      having a definite episode of hypoglycaemia at some stage are more acidotic and
      have greater evidence of renal impairment than those who are never hypoglycaemic
      (mean base excess -14.4 vs. -7.2, p < 0.001, mean creatinine 97 vs. 64, p < 0.001
      and mean urea 8.1 vs. 5.8, p = 0.03, respectively). These data do not support a
      role for reduced gluconeogenic substrate supply in the pathogenesis of
      hypoglycaemia in severe childhood malaria, but do support the hypothesis that
      gluconeogenesis is impaired. Commonly-used bedside blood glucose monitoring
      devices may overestimate blood glucose measurements in the normal range, and
      paradoxically may also seriously overestimate the frequency of hypoglycaemia.

PMID- 9604072
TI  - Tumour necrosis factor alpha as a predictor of impaired peak leg blood flow in
      patients with chronic heart failure.
AB  - Tumour necrosis factor alpha (TNF alpha) is increased in patients with cardiac
      cachexia, a condition associated with reduced peripheral blood flow both at rest
      and after interventions causing vasodilation. By contrast, in patients with
      chronic heart failure (CHF), higher TNF levels are associated with a greater
      capacity for vasodilation in the arm. To clarify the relationship between
      peripheral blood flow and TNF in CHF, we studied the relation between TNF alpha
      and blood flow in the leg (plethysmography, post maximal exercise and 5 min
      ischaemia) in 34 patients (age 63 +/- 2 years, ejection fraction 29 +/- 3%, peak
      VO2 16.6 +/- 1.1 ml/kg/min, mean +/- SEM). Peak leg blood flow correlated
      significantly with total TNF alpha (r = 0.68, p < 0.0001, peak VO2 (r = 0.54),
      and soluble TNF receptors 1 (r = 0.56) and 2 (r = 0.52, all p < 0.002). TNF
      alpha, soluble TNF receptors 1 and 2 and aldosterone correlated with peak blood
      flow independently of age, ejection fraction, peak VO2 and functional NYHA class.
      TNF alpha was the only parameter that showed strong correlations for peak blood
      flow in all clinically relevant subgroups (severe vs. mild, ischaemic vs.
      dilated, cachectic vs. non-cachectic patients). This study shows a close and
      inverse relationship between peak leg blood flow and the plasma concentration of
      TNF alpha, suggesting a pathophysiological role for TNF alpha in reducing peak
      peripheral blood flow in CHF.

PMID- 9604073
TI  - Management of intracerebral lesions in patients with HIV: a retrospective study
      with discussion of diagnostic problems.
AB  - A total of 95 patients who presented in 1994 and 1995 with focal brain lesions at
      a London HIV centre were studied retrospectively. Patients were allocated to
      "definite" or "presumed" diagnostic categories of toxoplasma encephalitis (TE),
      primary CNS lymphoma (PCNSL) or progressive multifocal leukoencephalopathy (PML),
      based on strict criteria. The number in each category was: TE, 20; PCNSL, 9; PML,
      7; presumed TE, 12; presumed PCNSL, 8 and presumed PML, 17. There were 20
      patients in whom a diagnosis could not be made, and there were three non-HIV
      diagnoses. Demographic data, features at presentation and routine CSF analysis
      were not discriminatory in making a diagnosis. Toxoplasma titres were a median of
      1:256 in those with TE compared to 1:16 in all other groups (p < 0.001) and those
      with TE were less likely to be on toxoplasma prophylaxis compared to those with
      PCNSL (p < 0.002). Survival with TE (median of 446 days) was significantly longer
      than survival in all other groups. Survival with either confirmed or presumed PML
      was similar. The problems of diagnosis of focal brain lesions in HIV patients are
      discussed and a management flow chart for mass lesions is proposed.

PMID- 9604074
TI  - Churg-Strauss syndrome in a district hospital.
AB  - Published series on Churg-Strauss syndrome (CSS) come from tertiary referral
      centres. We retrospectively studied 23 patients with CSS (18 male) seen over 14
      years (1982-1995) in a District General Hospital serving a population of 500,000.
      Mean age of onset of vasculitis was 57, 10-19 years older than in previous
      series. The commonest clinical features were asthma (22) and eosinophilia > 1.5 x
      10(9)/l (21). Systemic vasculitis involving two or more extrapulmonary organs
      occurred in 22 patients, with specific organ involvement of nervous system (18),
      joints (13), muscles (13), lungs (11), skin (11), kidneys (11), heart (10), and
      bowel (7). Various classification systems were applied including the Lanham
      criteria, which were met in 19 patients; the American College of Rheumatology
      criteria, met in 14; Churg and Strauss criteria, met in four; and the Chapel Hill
      Consensus definition, met only in two. ANCA was detected in 10/17 patients where
      measured. Treatment included corticosteroids (21), cyclophosphamide (8),
      azathioprine (9), immunoglobulin (2), and methotrexate (1). During follow-up six
      patients died, two due to myocardial vasculitis (mean age 52 years), three due to
      infection (mean age 80 years), and one cause unknown. Significant long-term
      disability was due to asthma in five and neuropathy in six.

PMID- 9604075
TI  - The outcome of bleeding duodenal ulcer in the era of H2 receptor antagonist
      therapy.
AB  - We studied 2119 patients presenting with duodenal ulcer as sole lesion, in the
      period 1976-1993, the era of H2 receptor antagonist (H2RA) therapy, prior to the
      introduction of Helicobacter pylori eradication. We used clinical assessment and
      serial check endoscopy to investigate the incidence of bleeding at presentation
      (group I, n = 286, 13.5%), the long-term outcome in this group and in that
      presenting with pain alone (group II, n = 1833, 87%) with respect to ulcer
      recurrence and bleeding, and the effect of H2RA maintenance therapy. Most
      patients were treated with H2RA, principally cimetidine. In group I, seven
      patients died early on; 38 had urgent surgery, of whom six died post-operatively.
      The remainder were treated; five immediately re-bled, of whom three were operated
      on. On follow-up, 98/227 group I patients relapsed, 21 (21%) of whom rebled.
      Relapse in group II was 1017/1668, with only 42 (4%) bleeding (p < 0.001). In
      patients without maintenance treatment, relapse was markedly higher (50/78 group
      I, 529/742 group II), but group II still bled significantly less (20% group I vs.
      3% group II). Relapse on maintenance was: 48/149 with five (10%) rebleeding in
      group I, and 488/926 with five (1%) bleeding in group II (p < 0.001). Despite the
      introduction of H2RA therapy, patients presenting with haemorrhage still have a
      risk of bleeding at ulcer relapse about 7-fold higher than that for those
      presenting with pain alone.

PMID- 9604076
TI  - Atypical chest pain: looking beyond the heart.
AB  - Chest pain is common, and tends to be overinvestigated. Patients with normal
      coronary anatomy have a low mortality, but remain significantly incapacitated. We
      discuss ways of improving the management of such patients. An early diagnosis of
      a non-cardiac cause of pain should be made, ideally by the general practitioner,
      taking account of risk factors for cardiac as well as psychological disorders,
      the quality of the pain, the patient's concerns and worries and the presence of
      stressful life events. The minimum of investigation should be performed.
      Cardiological referral should be considered for patients with a high a priori
      risk of ischaemic heart disease. Otherwise referral, if necessary, should be to a
      gastroenterologist, psychiatrist or clinical psychologist, as appropriate.
      Treatment options are medications with musculoskeletal or oesophageal activity,
      simple or repeated reassurance, cognitive therapy, psychiatric drugs, and
      respiratory retraining. We suggest that a multidisciplinary chest-pain clinic may
      improve the care of such patients.

PMID- 9604077
TI  - Natural kinds, the clinician-researcher and psychiatric diagnoses.

PMID- 9604078
TI  - A patient with falciparum malaria and bilateral gangrene of the feet who
      developed arrhythmia/ventricular fibrillation after quinine therapy.

PMID- 9604079
TI  - The Walrus and the Carpenter.

PMID- 9604080
TI  - The motion vision of the blind and the modularity of consciousness.
AB  - Humans blinded by lesions of the primary visual receiving cortex, area V1, can
      sometimes see certain attributes of the visible world, and in particular motion,
      crudely but consciously. This article examines why and enquires into the insights
      to be drawn from such a study.

PMID- 9604081
TI  - London at war.

PMID- 9604082
TI  - The role of the expert witness in medical negligence actions.

PMID- 9604083
TI  - The evolution of the medical facilities in British motor racing, 1964 until 1990.

PMID- 9604084
TI  - Radiation in the public eye: for better or for worse?

PMID- 9604085
TI  - Silastic breast implants--the medicolegal position (summary).

PMID- 9604086
TI  - Lettsomian Lecture. Intestinal fistula--a surgeon's nightmare: a physiologist's
      dream.

PMID- 9604087
TI  - Primary care initiatives in rural Hampshire. A vision for health care.

PMID- 9604088
TI  - Information technology for the technologically incompetent.

PMID- 9604089
TI  - Public health care: dragonfly or dinosaur?

PMID- 9604090
TI  - The annual oration "the doctors' charter".

PMID- 9604092
TI  - A Bosnian diary.

PMID- 9604093
TI  - Sir John McNee bequest. Outcome of both cardiovascular and gastrointestinal
      surgical intervention in Down's syndrome.

PMID- 9604094
TI  - Rod photoresponses in 6-week and 4-month-old human infants.
AB  - Rod-only electroretinograms (ERGs) were recorded from 6-week and 4-month-old
      normal human infants. The leading edge of the rod a-wave was fitted with a model
      of the activation phase of phototransduction to provide estimates of S (a
      sensitivity parameter) and RmP3 (the maximum saturated photoreceptor response) at
      each of the investigated ages. Both S and RmP3 increased over the first postnatal
      months but followed different developmental time courses with S approaching adult
      like values sooner than RmP3. The changes in S and RmP3 can be interpreted within
      the context of a model incorporating the combined effects of increased levels of
      rhodopsin and the changing structure of the rod outer segment during development.

PMID- 9604096
TI  - Visual half-field development in children: detection of colour-contrast-defined
      forms.
AB  - Recently we have shown that children's ability to perceive motion-defined forms
      shows an asymmetry in the left and right visual half-fields which disappears in
      adulthood. The present study is focused on the visual half-field development of
      colour contrast vision in the same group of subjects. It was found that colour
      contrast thresholds for the detection of colour-contrast-defined forms decrease
      with age to reach adult values around puberty. This improvement of colour
      contrast vision with age is attributed to the maturation of cortical mechanisms.
      However, in contrast to a visual half-field asymmetry for motion detection during
      childhood, no visual half-field differences were observed for colour contrast
      detection in children.

PMID- 9604095
TI  - Interactions between global motion and local binocular rivalry.
AB  - Binocular rivalry is thought to arise from a low-level cortical site. Experiment
      1 evaluates this claim with respect to local and global motion processing by
      using a multiple-aperture motion stimulus and measuring the predominance of
      global coherence while one of the component gratings is engaged in rivalry.
      Results show that rivalry suppression of the component grating precludes global
      coherence. Presumable, suppression prevents the component motion signal from
      advancing to higher-level global motion areas, suggesting rivalry occurs between
      local and global motion processing. However, feedback from higher-level
      mechanisms might exert an influence on binocular rivalry and thus Experiment 2
      measures how the predominance of a local target engaged in binocular rivalry with
      a competing local stimulus is affected when the target forms part of a globally
      coherent motion stimulus. The augmented level of target predominance during
      global motion relative to local motion indicates that higher-level motion
      mechanisms can feedback and influence the binocular rivalry process. Together,
      these data imply a looping hierarchy of motion processing stages, with rivalry
      suppression transpiring at an intermediate level and subject to feedback from
      higher-level motion areas.

PMID- 9604097
TI  - Visual half-field development in children: detection of motion-defined forms.
AB  - It is widely accepted that the maturation of the extrastriate cortex is not
      completed before late puberty. To gain insight into the functionality of the
      extrastriate cortex during normal development, we tested a group of 21 children
      (age 6-16 years) on their ability to detect motion-defined forms. With a two
      alternative forced-choice procedures we determined thresholds and visual half
      field asymmetries (i.e., left vs right) for detection of relative motion. It was
      found that children had higher thresholds than adults. Furthermore, children had
      more difficulty with the detection of motion in the left than right half-field,
      whereas the control group of 33 adults (age 21-55 years) performed similarly in
      both visual half-fields. These results are discussed in the light of a
      hemispheric asymmetry in the maturation of the extrastriate cortex.

PMID- 9604098
TI  - Stereoscopic segregation of transparent surfaces and the effect of motion
      contrast.
AB  - Stereoscopic segregation in depth was studied using two superimposed
      frontoparallel surfaces displayed in dynamic random dot stereograms. The two
      patterns were positioned symmetrically in front of and behind a binocular
      fixation point. They were either stationary, or they could move relative to each
      other. Sensitivity for segregation was established by adding gaussian distributed
      disparity noise to the disparities specifying the two planes, and finding the
      noise amplitude that gave threshold segregation performance. Observers easily
      segregate the two surfaces for disparity differences between approximately 6 and
      30-40 arcmin. Motion contrast, which by itself provides no cue to perform the
      task, greatly improves sensitivity for segregation. Noise tolerance rises by a
      factor of two or more when the patterns move at different speeds, or in different
      (frontoparallel) directions. The effect increases with directional difference,
      but the optimal directional difference deviated from 180 deg. The optimal speed
      varies with disparity difference. Thus, motion and disparity must interact in
      order to resolve the two transparent planes.

PMID- 9604099
TI  - Attentional selection by distractor suppression.
AB  - Selective attention was studied in displays containing singletons popping out for
      their odd form or color. The target was defined as the form-singleton, the
      distractor as the color-singleton. The task was to discriminate the length of a
      longer line inside the target. Target-distractor similarity was controlled using
      a threshold measurement as dependent variable in experiments in which distractor
      presence vs absence, bottom-up vs top-down selection (through knowledge of target
      features), and target-distractor distance were manipulated. The results in the
      bottom-up condition showed that length threshold was elevated when a distractor
      was present and that this elevation progressively increased as the number of
      distractors was increased from one to two. This set-size effect was not accounted
      by the hypothesis that selective attention intervenes only at the stage of
      decision before response. Selective attention produced a suppressive surround in
      which discriminability of neighboring objects was strongly reduced, and a larger
      surround in which discriminability was reduced by an approximately constant
      amount. Different results were found in the top-down condition in which target
      discriminability was unaffected by distractor presence and no effect of target
      distractor distance was found. On the other hand, response times in both bottom
      up and top-down conditions were slower the shorter the target-distractor distance
      was. On the basis of the experimental results, selective attention is a parallel
      process of spatial filtering at an intermediate processing level operating after
      objects have been segmented. This filtering stage explores high level
      interactions between objects taking control on combinatorial explosion by
      operating over only a limited spatial extent: it picks out a selected object and
      inhibits the neighboring objects; then, non-selected objects are suppressed
      across the overall image. When no feature-based selection is available in the
      current behavior, this filtering influences perception in decreasing
      discriminability of non-selected objects. When feature-based selection is
      available, spatial interactions are set before stimulus arrival, hence only the
      unmatching objects have their discriminability diminished.

PMID- 9604100
TI  - The effect of photon noise on the detection of white flashes.
AB  - Thresholds for detecting brief, white, foveal test flashes drop abruptly within
      0.2 sec of the offset of a white adapting field. The magnitude of the abrupt drop
      is proportional to the square root of field intensity (square root of I) correct
      for bleaching and dark light. Thresholds are then stable out to 1.6 sec for 200
      msec tests, or recover only slightly for 20 msec tests. These results exclude
      some simple deterministic models in which Weber-like gain controls in the
      luminance pathway are assumed to recover exponentially in the dark, but can be
      explained parsimoniously if turning off the field abolishes photon-driven noise,
      improving the S/N ratio while leaving visual responsivity virtually unaltered.
      This theory was first put forward by Krauskopf and Reeves [(1980) Vision
      Research, 20, 193-196] for S-cone thresholds; it implies that the Weber law for
      increment thresholds is not due to a single gain control, but rather expresses
      the product of two distinct square root of I factors, adjustment of responsivity
      and photon-driven noise. Removal of the noise, not recovery of gain, permits
      thresholds to fall in early dark adaptation.

PMID- 9604101
TI  - Luminance contrast and spatial-frequency tuning of the transient-vergence system.
AB  - Vergence has transient components that are stimulated by brief presentations of
      stimuli at large disparities (up to several degrees). The question that we have
      addressed is what stimulus features are encoded by this system. A competition
      paradigm [Jones & Kerr, (1972)]. Vision Research, 12, 1425-1430) was used in
      which three gabors were presented. A single Gabor was presented to the fovea of
      one eye and two gabors, 2.5 deg to either side of the fovea, to the other; one of
      which, when paired with the single Gabor defined a convergent direction, the
      other a divergent direction. First we determined if increasing the luminance
      contrast of the Gabor pair whose disparity was opposite to the observer's
      response-bias direction (variable-contrast pair) relative to the remaining Gabor
      (reference) could alter the observer's response direction. Secondly, we
      determined if the contrast required for such a change in response was affected by
      the relative spatial frequency of the convergent and divergent Gabors. The
      reference Gabor was held at 2 cpd and the variable Gabor pair was varied between
      5.6 and 0 (a gaussian) cpd. Results demonstrated that increasing the luminance
      contrast of the variable pair relative to the reference Gabor could alter the
      observer's response direction, even when the contrast of only one of the variable
      pair Gabors was increased. The luminance contrast required for this change to
      occur was directly related to the spatial frequency of the variable pair over the
      entire frequency range tested. Vergence responses were preferentially made to
      lower spatial frequencies, even when a low spatial frequency was pared with a
      high one. We conclude that transient-vergence responses are not reduced by mixed
      contrasts (i.e. no contrast-paradox effect) and appear to be mediated by a system
      that employs a single lowpass sensitive channel.

PMID- 9604102
TI  - Extraction of perceptually salient contours by striate cortical networks.
AB  - We present a cortical-based model for computing the perceptual salience of
      contours embedded in noisy images. It has been suggested that horizontal intra
      cortical connections in primary visual cortex may modulate contrast detection
      thresholds and pre-attentive "pop-out". In our model, horizontal connections
      mediate context-dependent facilitatory and inhibitory interactions among oriented
      cells. Strongly facilitated cells undergo temporal synchronization; and
      perceptual salience is determined by the level of synchronized activity. The
      model accounts for a range of reported psychophysical and physiological effects
      of contour salience. In particular, the model proposes that intrinsic properties
      of synchronization account for the increased salience of smooth, closed contours.
      Application of the model to real images is demonstrated.

PMID- 9604103
TI  - A model of neuronal responses in visual area MT.
AB  - Electrophysiological studies indicate that neurons in the middle temporal (MT)
      area of the primate brain are selective for the velocity of visual stimuli. This
      paper describes a computational model of MT physiology, in which local image
      velocities are represented via the distribution of MT neuronal responses. The
      computation is performed in two stages, corresponding to neurons in cortical
      areas V1 and MT. Each stage computes a weighted linear sum of inputs, followed by
      rectification and divisive normalization. V1 receptive field weights are designed
      for orientation and direction selectivity. MT receptive field weights are
      designed for velocity (both speed and direction) selectivity. The paper includes
      computational simulations accounting for a wide range of physiological data, and
      describes experiments that could be used to further test and refine the model.

PMID- 9604105
TI  - Posterior tibial tendon insufficiency. Its Diagnosis, Management, and Treatment.
AB  - Posterior tibial tendon dysfunction, once thought to be a rare clinical entity,
      has been observed to be a major cause of acquired flatfoot deformity in adults.
      Several risk factors have been identified, ranging from inflammatory conditions
      to obesity. A physical examination using a series of tests, including the single
      limb rise, first-metatarsal rise sign, and the "too-many-toes" sign, used in
      combination with selected radiographic imaging techniques, allows classification
      of the severity of disease. This staging system then serves as the basis for
      formulating the treatment options, which include nonoperative as well as
      operative alternatives. Conservative treatment involves rest, anti-inflammatory
      medication, orthotic devices, and modifications to shoes. Operative options are
      numerous and include primary tendon repair, tendon transfer, osteotomies, and
      arthrodesis.

PMID- 9604104
TI  - Microperimetry of localized retinal nerve fiber layer defects.
AB  - The aim of this study was to determine the sensitivity of retinal areas involved
      in a localized retinal nerve fiber layer (RNFL) defect and to assess correlations
      between microperimetry and the standard full threshold central 30 deg visual
      field test. Twenty-five patients with focal RNFL defects, evaluated by means of
      Argon-blue scanning laser ophthalmoscopy (SLO), underwent an automated 30 deg
      central visual field examination and a microperimetry with SLO. Microperimetry
      was performed according to standard procedures (infrared laser for fundus
      imaging; HeNe laser for 10 candles/m2 background illumination, fixation aid and
      generation of stimuli; manual fundus tracking). The size of stimuli was Goldmann
      III with 0.1 sec duration. In eyes with focal RNFL defects a deep microperimetric
      scotoma of at least 5 dB was found in 12 cases and a mild scotoma (1-4 dB) in 13
      cases. These scotomas were mainly located throughout the whole defect or grouped
      in the temporal or nasal sides of the defect and were characterized by sharp and
      well-defined borders. With automated perimetry, a scotoma, defined by a single
      point depression of at least 10 dB or a depression of at least 5 dB in two or
      more contiguous points corresponding to the RNFL, defect, was found in only 14
      out of 25 eyes with microperimetric defect. Focal RNFL defects correspond to
      localized areas of depressed retinal sensitivity as evaluated by microperimetry.
      The close correspondence between structural and microperimetric findings suggests
      that, in hypertensive eyes also, localized RNFL defects correspond to visual
      dysfunction possibly associated with substantial atrophy of ganglion cells.

PMID- 9604106
TI  - Avascular necrosis in systemic lupus erythematosus: clinical associations and a
      47-year perspective.
AB  - Twenty-six of 488 (5%) patients with systemic lupus erythematosus followed in a
      private practice developed clinically evident, symptomatic avascular necrosis.
      Avascular necrosis was significantly associated with hypertension, pleural
      effusions, cerebritis, nephritis, anemia, and earlier age of disease onset. No
      association with anticardiolipin antibodies or thromboembolic disease was
      observed. Avascular necrosis is usually observed in active, severe lupus.

PMID- 9604107
TI  - The effect of surface coating of femoral prostheses implanted without cement: a 2
      to 4-year follow-up study.
AB  - A randomized, concurrently controlled, prospective, single-blinded, multicenter
      study was done to evaluate the effect of proximal surface coating of a femoral
      prosthesis on clinical and radiographic results of cementless total hip
      arthroplasty (THA). The Profile femoral prosthesis (DePuy, Warsaw, IN), an
      anatomic titanium alloy stem, was used in one of three configurations: (1)
      smooth, (2) porous coated, or (3) hydroxyapatite (HA) coated. Ninety-one cases
      were enrolled in the study, with seven cases lost to follow-up and 79 cases
      available for clinical review with 24- to 48-month follow-up. The study shows
      that HA-coated stems performed as well, if not better than, porous-coated or
      smooth stems. Results show HA-costed stems with statistically superior total
      Harris hip scores (microHA = 96.0) than smooth stems (microS = 85.1) (Student's t
      test, P = 0.004). This was primarily due to differences between the functional
      score of the two groups (microHA - 31.6; microS = 27.9, P = 0.003). Porous-coated
      stems were intermediate in performance (microPC = 89.8), with hip scores that
      were statistically indistinguishable from both smooth and HA-coated stems. Our
      data support the hypothesis that clinical differences exist and are attributable
      to the type of surface coating used for the cementless femoral components in THA.

PMID- 9604108
TI  - Saline injection technique to confirm pedicle screw path: a cadaveric study.
AB  - Pedicle screws are frequently misdirected during placement, which may lead to
      complications such as pedicle fracture, inadequate biomechanical strength, and
      neurologic deficit. Roentgenographic confirmation and manual probing are
      important but are not 100% accurate. We have developed a simple saline injection
      technique to assist in confirming the correct path of the pedicle screw prior to
      its insertion. In this study, five fresh frozen cadaveric spines were dissected
      from T-12 to L-5, and a total of 60 data points were recorded. Saline injection
      tests confirmed 31 of 32 (97%) drill paths that were in the pedicles. Two
      specimens were used to intentionally misdirect the pedicle drill path to
      determine the rate of false-negative results. Pedicle drilling was misdirected
      medially, laterally, superiorly, and and inferiorly (six of each). There were a
      total of 24 intentional and four unintentional, radiographically confirmed missed
      drillings of the pedicle. Of the 28 misdirected pedicle paths, the saline
      injection test correctly diagnosed the problem in 23 (82%) cases. Seven
      misdirected drillings were falsely negative by the injection test (five superior
      and two inferior directions). This study shows that a simple saline injection
      test can be a useful adjunct in confirming a correct pedicle path in 97% of the
      cases. If an incorrect path has been created, false-negative tests are possible
      in 18% of the cases.

PMID- 9604109
TI  - The role of the abductor pollicis brevis in opposition.
AB  - The abductor pollicis brevis muscle is the most significant of the thenar
      intrinsics with respect to providing palmar abduction and pronation of the thumb.
      While limited, even clinically acceptable, function may be exhibited in its
      absence, the abductor pollicis brevis is required for full opposition (thumb tip
      to base of small finger).

PMID- 9604110
TI  - Skin necrosis complicating functional bracing.
AB  - We report a complication associated with functional bracing of a metacarpal shaft
      fracture that required operative intervention. A 30-year-old man with a closed,
      dorsally angulated, metacarpal shaft fracture of the right ring finger was
      treated with a functional brace. During brace immobilization, the patient
      developed full-thickness skin necrosis on the dorsum of the right hand. The
      patient underwent surgical debridement of the ulcerated area and fracture
      stabilization with an intramedullary Kirschner wire. Patients treated with a
      metacarpal brace should be instructed to release the strap every 5 to 6 hours for
      a short period to allow restoration of blood flow to the potentially ischemic
      skin.

PMID- 9604111
TI  - Castleman's disease in the extremity.
AB  - Castleman's disease is an uncommon entity that is characterized by lymphoid
      hyperplasia with two variants: the hyaline vascular type and the plasma cell
      type. We present a case affecting the lower extremity, an extremely rate site of
      the disease.

PMID- 9604113
TI  - Predicting intramedullary nail length.

PMID- 9604112
TI  - Masked rotatory subluxation of the atlas associated with fracture of the
      clavicle: a clinical and biomechanical analysis.
AB  - We report on two children who developed a fixed rotatory subluxation of the
      atlantoaxial joint due to torticollis being attributed to a fractured clavicle.
      Appropriate treatment was delayed for weeks to months; only after the fractured
      clavicle had healed and the torticollis persisted was the problem identified.
      Persisting rotatory subluxation also predisposes to further anterior displacement
      of C-1 due to an increased moment arm created by the forward displacement of the
      center of gravity of the head. The association of atlantoaxial subluxation should
      always be considered in children presenting with a clavicular fracture and an
      acute torticollis.

PMID- 9604114
TI  - Pavlovian conditioning of sexual interests in human males.
AB  - Pavlovian conditioning of the human male sexual response may be involved in the
      ontogenetic development of sexual interests and may be responsible for individual
      differences. We attempted to demonstrate Pavlovian conditioning of sexual
      interests in a nonclinical sample of adult males. Ten participants were exposed
      to 11 pairings of a slide of a moderately attractive, partially nude female adult
      (TARGET) and a highly arousing videotape depiction of heterosexual sexual
      interactions (US). Ten other participants were exposed to 11 presentations of the
      TARGET alone. Participants exposed to the TARGET-US contingency showed a 10%
      relative increase in sexual arousal to the TARGET; participants exposed to the
      TARGET-ALONE contingency showed an 11% relative decrease in sexual arousal to the
      TARGET. This group difference is interpreted as resulting from both conditioning
      and habituation.

PMID- 9604115
TI  - Effects of physical appearance on masculine trait ratings of boys and girls with
      gender identity disorder.
AB  - University students, masked to group status, rated the physical appearance of
      boys and girls with gender identity disorder (GID) and same-sex controls using
      traits with stereotypical masculine connotations (for boys: all-boy, handsome,
      masculine, and rugged; for girls: handsome, masculine, rugged, and tomboyish).
      Three traits (all-boy, masculine, and rugged) were judged to be significantly
      less characteristic of the boys with GID as compared to the same-sex controls;
      for the fourth trait (handsome), the inverse result was obtained. All four traits
      (handsome, masculine, rugged, and tomboyish) were judged to be significantly more
      characteristic of the girls with GID as compared to the same-sex normal and/or
      clinical controls. These results were the inverse of the results obtained in two
      previous experiments, in which traits with stereotypical feminine connotations
      were used (Fridell et al., 1996; Zucker et al., 1993). Taken together, the
      results suggest that boys and girls with GID have a sex-typed physical appearance
      that distinguishes them from same-sex controls. Possible determinants of these
      differences are discussed.

PMID- 9604116
TI  - Sleepsex: a variant of sleepwalking.
AB  - Sexual acts performed by a sleeping subject have been rarely reported. Two cases
      are now presented involving sexual behavior performed while asleep. The first
      case involves the hitherto unreported association of sleepsex with sleepeating.
      The second case concerns a rarely reported act of sexual battery by a known
      sleepwalker, and the use of somnambulism as a legal defense. Sexual behavior in
      sleep may be pleomorphic and more common than realized in both the patient and
      normal populations.

PMID- 9604118
TI  - Sex and the quality of life in Denmark.
AB  - From a representative sample of 2460 Danish citizens, ages 18 to 88, anonymous
      answers were obtained to a 317-item quality-of-life (QL) questionnaire, which
      included five questions on sexuality. Among the respondents in the sample, 1.2%
      reported they were bisexual and 0.9% homosexual. Although sexual problems were
      found in all age groups, lack of a suitable sex partner and inability to achieve
      orgasm were more common among the young and erectile dysfunction more common
      among the old. Most frequent problems among the women were reduced sexual desire
      (11.2%) and the lack of a suitable sex partner (4.9%), and among the men, the
      lack of a suitable sex partner (7.3%) and erectile dysfunction (5.4%). The QL of
      persons with sexual problems was from 1.2 to 19.1% lower than the population mean
      (as expressed in terms of this mean). The intermediate sized covariation between
      sexual problems and the QL suggests that such problems can be symptoms of a
      reduced QL rather than medical problems to be tackled through medical
      intervention or sex therapy proper. Implications for a quality-of-life-sensitive
      clinical practice are discussed.

PMID- 9604117
TI  - Australian and South African undergraduates' HIV-related knowledge, attitudes,
      and behaviors.
AB  - To understand safe sex behavior in two countries which have been differentially
      affected by the HIV/AIDS epidemic, the present study compared the AIDS-related
      knowledge, attitudes, and behaviors of 920 heterosexual undergraduate students in
      Australia and 228 heterosexual undergraduate students in South Africa. South
      African students were found to have significantly less knowledge about HIV/AIDS,
      and significantly less favorable attitudes toward safe sex behavior than their
      Australian counterparts. They were also more likely to report that they have
      avoided various groups of people for fear of contracting AIDS. Experience from
      Australia over the period 1986-1995 suggests that significant improvements in the
      AIDS-related knowledge, attitudes, and behaviors of South African undergraduates
      are achievable.

PMID- 9604119
TI  - The frequency of sexual dysfunctions in patients attending a sex therapy clinic
      in north India.
AB  - Analyzed data on 1000 consecutive patients with sexual disorders attending the
      psychosexual clinic at the All India Institute of Medical Sciences. The majority
      of patients were educated males between 21 and 30 years of age, belonging to the
      middle class. There was a slight preponderance of married patients. Fifty-two
      percent of patients had premarital or extramarital sexual contact; less than 5%
      had had homosexual contact; 10% had no sexual contact. Most patients had more
      than one complaint. Premature ejaculation (77.6%) and nocturnal emission (71.3%)
      were the most frequent problems followed by a feeling of guilt about masturbation
      (33.4%) and small size of the penis (30%). Erectile dysfunction was a complaint
      of 23.6%. Excessive worry about nocturnal emission, abnormal sensations in the
      genitals, and venereophobia was reported in 19.5, 13.6, and 13% of patients,
      respectively. Only 36 female patients attended the clinic with their spouses.

PMID- 9604120
TI  - Carrier-mediated intestinal absorption of valacyclovir, the L-valyl ester prodrug
      of acyclovir: 1. Interactions with peptides, organic anions and organic cations
      in rats.
AB  - The mechanism of intestinal transport of valacyclovir (VACV), the L-valyl ester
      prodrug of acyclovir, was investigated in rats using an in situ intestinal
      perfusion technique. VACV demonstrates an oral bioavailability that is three to
      five time greater than acyclovir, concentration dependent, and saturable in
      humans. Homogenate and perfused buffer stability results demonstrated that VACV
      was increasingly unstable with increasing pH. VACV was converted to ACV in a
      concentration dependent manner during a single pass through the intestinal
      segment. Perfusions were performed at 37 degrees C, pH 6.5, and under iso-osmotic
      conditions (290 +/- 10 mOsm L-1). Intestinal outlet concentrations were corrected
      for VACV that was converted to ACV during the perfusion. The effective
      dimensionless intestinal permeability (P*e) of VACV was concentration dependent,
      saturable (intrinsic Km = 1.2 +/- 0.7 mM), and significantly reduced (p < 0.05)
      in the presence of peptide analogues (amoxicillin, ampicillin, cefadroxil, and
      cephradine), by the organic anion, p-amino hippuric acid and by the organic
      cation quinine. VACV transport was not inhibited by classical nucleoside
      competitive substrates or inhibitors or by valine. These results suggest that
      H(+)-oligopeptide, H(+)-organic cation, and organic anion transporters are
      involved in the small intestinal uptake of VACV. The permeability of VACV in the
      colon was very low, indicating that VACV is predominantly absorbed from the small
      intestine. VACV P*e was not altered in the presence of glucose-induced convective
      fluid flow, suggesting that carrier-mediated, transcellular uptake is the
      predominant absorption pathway of VACV in rat small intestine. Based on these
      results, the oral bioavailability of VACV appears to be significantly influenced
      by the preabsorptive conversion of VACV to the poorly absorbed ACV, by the
      involvement of multiple transporters in VACV small-intestinal uptake, and by the
      low permeability of VACV in the colon.

PMID- 9604121
TI  - Pharmacokinetics and tissue distribution of a new carbapenem DA-1131, after
      intravenous administration to mice, rats, rabbits and dogs.
AB  - The pharmacokinetic parameters including tissue distribution and/or biliary
      excretion of DA-1131, a new carbapenem, were evaluated after intravenous (iv)
      administration to mice, rats, rabbits, and dogs. After i.v. administration to
      mice (20, 50, 100, and 200 mg kg-1), rats (50, 100, 200, and 500 mg kg-1),
      rabbits (20, 50, 100, and 200 mg kg-1), and dogs (10, 20, 50, 100, and 200 mg kg
      1), the pharmacokinetic parameters of DA-1131 seemed to be independent of DA-1131
      doses studied in all four animal species. However, the renal clearance of
      percentage of i.v. dose of DA-1131 excreted in 24 h urine as unchanged drug
      decreased significantly in rabbits (from 200 mg kg-1) and dogs (from 100 mg kg-1)
      due to reduced kidney function induced by DA-1131. The creatinine clearance
      decreased significantly in rabbits at 200 mg kg-1 compared with that in the
      control rabbits (0.466 versus 4.31 mL min-1 kg-1). Renal active secretion of DA
      1131 was observed in rabbits and was less considerable in rats, but renal active
      reabsorption of DA-1131 was observed in dogs. Although DA-1131 was widely
      distributed in all tissues studied in mice (20-200 mg kg-1), rats (200 mg kg-1),
      rabbits (50 mg kg-1), and dogs (50 mg kg-1) affinity of DA-1131 for tissues was
      low: the tissue-to-plasma concentration ratios were greater than unity only in
      the kidney and/or liver. The low affinity of DA-1131 for tissues was also
      supported by relatively low values of the apparent volume of distribution at
      steady state in rats (147-187 mL kg-1), rabbits (91.7-148 mL kg-1), and dogs 243
      298 mL kg-1). The contribution of biliary excretion of unchanged DA-1131 to
      nonrenal clearance of DA-1131 seemed to be minor in rats (200 mg kg-1) and dogs
      (50 mg kg-1); the percentages of i.v. dose excreted in 8 h bile as unchanged DA
      1131 were 1.76 and 2.71% after i.v. administration of the drug to rats and dogs,
      respectively.

PMID- 9604122
TI  - Interspecies pharmacokinetic scaling of a new carbapenem, DA-1131, in mice, rats,
      rabbits and dogs, and prediction of human pharmacokinetics.
AB  - The total body clearance (CI), renal clearance (CIr), and apparent volume of
      distribution at steady state (Vss) of DA-1131, a new carbapenem, after
      intravenous (iv) administration of the drug, 50 mg kg-1, to mice, rats, rabbits,
      and dogs were analysed as a function of species body weight (W) using the
      allometric equation for interspecies scaling, and were used to predict these
      parameters in humans. Significant linear relationships were obtained between
      log[CI (L h-1)] and log[W (kg)] (r = 0.995; p = 0.00503), log [CI, (L h-1)] and
      log [W (kg)] (r = 0.998; p = 0.0429), and log [Vss (L)] and log [W (kg)] (r =
      0.987; p = 0.0126). The corresponding allometric equations were CI = 0.706W 0811,
      CIr = 0.318W 0.888, an V88 = 0.194W 0981. These allometric equations were
      extrapolated to predict the CI and Vss for DA-1131 in humans based on 70 kg body
      weight. The CI and Vss for humans predicted from the four animal data well fitted
      to regression lines of animal data. Interspecies scale-up of plasma concentration
      time data for the four species using a complex Dedrick plot resulted in similar
      profiles. In addition, the concentration in plasma-time profile predicted that
      the DA-1131 data obtained from laboratory animals could be utilized to generate
      preliminary estimates of the pharmacokinetic parameters in humans. These
      parameters can serve as guidelines for better planning of clinical studies.

PMID- 9604123
TI  - The effect of age on the pharmacokinetics of valsartan.
AB  - Twelve young (mean age 23 years, range 18-28) and 12 elderly (mean age 76 years,
      range 65-89) volunteers were given a single oral dose of 80 mg valsartan after an
      overnight fast. Each group consisted of six male and six female subjects. Mean
      systemic exposure to valsartan was higher in the elderly when compared with the
      young (AUC(0-24 h), 52% increase and AUC(0-infinity), 70% increase). Variability,
      as shown by the coefficient of variation (CV), was larger for the elderly
      subjects and ANOVA of the log transformed AUC showed a significant difference
      between the two groups. This difference was largely brought about by five elderly
      subjects (one male, four females), whose AUC was about 2-fold higher than the
      rest of the group. For the remaining elderly subjects, plasma valsartan AUC was
      similar to that observed for the young volunteers. This higher systemic exposure
      in five of the elderly subjects is not thought to be of clinical relevance when
      data from the patient population are considered. Other covariates--such as body
      weight, comedication, creatinine clearance, valsartan kinetics (absorption rate,
      distribution, and elimination)--did not explain the higher AUC in this subset of
      the elderly group. Data from the present study were compared with population
      kinetic data obtained from larger clinical trials including hypertensive patients
      in all age groups. Using this population approach, there was no difference in the
      pharmacokinetics of valsartan between male and female patients. Also, a
      relationship between plasma clearance of valsartan and age was established. The
      median age of patients in the hypertensive pool was 55 years. For an average 70
      year-old patient, plasma clearance of valsartan is predicted to fall by 22%
      compared with an average 55-year-old. For the population this difference is not
      sufficient to warrant initial dose adjustment based on age per se. The covariate
      age, does not completely explain the variability in the pharmacokinetics of
      valsartan within the general population. The treatment was well tolerated.

PMID- 9604124
TI  - Artemisinin pharmacokinetics in healthy adults after 250, 500 and 1000 mg single
      oral doses.
AB  - Eight healthy male, Vietnamese subjects were administered 1 x 250, 2 x 250, and 4
      x 250 mg artemisinin capsules in a cross-over design with randomized sequence
      with a 7-day washout period between administrations. The inter-individual
      variability in artemisinin pharmacokinetics was large with parameter coefficient
      of variation (CV) typically between 50-70%. The parameter with the smallest
      variability was the elimination half-life (CV approximately equal to 30-40%).
      Analysis of variance indicated also a large intra-subject variability. (CV, or =
      24%) for the dose-normalized area under the plasma concentration-time curve
      (AUC/dose). The pharmacokinetic results suggested artemisinin to be subject to
      high pre-systemic extraction. Artemisinin half-life could not predict the extent
      of in vivo exposure to the drug, there being no correlation between half-life and
      oral clearance. Artemisinin oral plasma clearance was about 400 L h-1 exhibiting
      a slight decrease with dose, although the effect was weak. Thus results from
      studies using different artemisinin doses may, within the studied dose range, be
      compared without the complication of disproportionate changes in drug exposure
      with varying dose levels. Half-lives appeared to increase with dose. An observed
      period effect in the analysis of variance was tentatively associated with time
      dependency in artemisinin pharmacokinetics. There was a high correlation between
      artemisinin plasma concentrations determined at various time-points after drug
      administration and the AUCs after the 500 and 1000 mg doses, but less so after
      the 250 mg dose. This may show a tentative approach to assess the systemic
      exposure of the patients to artemisinin from the determination of artemisinin
      plasma concentrations in one or two plasma samples only. Artemisinin was well
      tolerated with no apparent dose or time dependent effects on blood pressure,
      heart rate or body temperature.

PMID- 9604125
TI  - Lack of renal secretion of carbenicillin in rats: poor affinity to the organic
      anion transporter at renal brush border membrane.
AB  - The renal secretion of carbenicillin (CBPC) was studied in rats. The results
      obtained in the in vivo study indicated very poor renal secretion of CBPC in
      rats, which was entirely different from those observed in humans and rabbits. In
      humans and rabbits, significant and stereoselective renal secretion of CBPC was
      observed in vivo. In order to verify the poor renal secretion of CBPC in rats,
      the transport characteristics of the organic anion transporters were studied in
      vitro using basolateral and brush border membrane vesicles. Transport of p
      aminohippuric acid (PAH) into the basolateral membrane vesicles (BLMVs) was
      inhibited by CBPC, indicating that the organic anion transporter located at the
      BLM may have affinity to CBPC. In contrast, the transport of PAH into the brush
      border membrane vesicles (BBMVs) was not inhibited by CBPC, suggesting that the
      organic anion transporter located at the BBM may not have affinity to CBPC.
      Similar results were obtained for sulbenicillin (SBPC). Since CBPC and SBPC exist
      as di-anions at physiological pH, the organic anion transporter located at the
      rat renal BBM may not exhibit affinity to water-soluble di-anions, which in turn
      will result in poor renal secretion of these compounds.

PMID- 9604126
TI  - The influence of food on the disposition of the antiepileptic rufinamide in
      healthy volunteers.
AB  - The effect of food on the pharmacokinetics of the antiepileptic rufinamide was
      investigated in healthy volunteers. Twelve subjects were treated with single pre
      oral doses of 600 mg of rufinamide after overnight fasting or a fat and protein
      rich breakfast. Mean (+/- S.D.) areas under the plasma concentration-time curves
      (AUCs) of the unchanged compound were 57.2 (16) micrograms mL-1 h when given to
      the fasted volunteers and 81.7 (22.2) micrograms mL-1 h (p = 0.0001) when given
      after the breakfast. The average AUC was increased by 44% when rufinamide was
      given with food and the maximum concentration (Cmax) by about 100%. The time at
      which Cmax was reached (tmax) was shorter (8 h in fasted conditions and 6 h in
      fed after breakfast); the terminal half-life was not influenced by concomitant
      intake of food.

PMID- 9604127
TI  - Rationale for influx enhancement versus efflux blockade to increase drug exposure
      to the brain.
AB  - Various methods of optimizing brain exposure to polar compounds have been
      examined. However, direct comparisons of the potential efficacy of these methods
      have not been forthcoming. The present study utilized a mathematical approach to
      compare the efficacy of two pharmacologic methods of improving brain drug
      distribution: uptake enhancement and efflux blockade. In the present simulation
      study, the pharmacokinetics of a hypothetical marker and modifier were described
      by differential equations. The relationship between modifier effect on marker
      uptake into, or efflux from, the brain and modifier concentration in serum
      (uptake enhancement) or brain tissue (efflux blockade) was described by the Hill
      equation. Uptake enhancement increased both the rate and extent of marker
      penetration into the brain. Efflux blockade resulted in delayed attainment of
      maximum marker concentration, and prolonged marker residence, in brain tissue.
      Under all conditions and doses examined, uptake enhancement was more effective
      than efflux blockade in maximizing brain tissue exposure to the marker. Although
      development of agents that enhance uptake of polar compounds may be limited by
      the potential deleterious effects of blood-brain barrier disruption, use of this
      approach in theory could represent a significant advancement in the treatment of
      brain disorders.

PMID- 9604128
TI  - Metabolic changes of acetaminophen after intravenous administration to rats
      pretreated with 2-(allylthio)pyrazine.

PMID- 9604129
TI  - A 21 point unifying hypothesis on the etiology and treatment of multiple
      sclerosis.
AB  - Multiple sclerosis (MS) is postulated to be a cell mediated autoimmune disease
      directed against central nervous system myelin components. Our understanding of
      the disease has been enhanced by a number of factors: 1) advances in our
      understanding of the immune system; 2) clinical trials which are beginning to
      identify treatments which can affect MS; 3) a better understanding of the
      clinical features of MS; and 4) advances in MRI imaging of the brain. Based on
      the current state of knowledge, this paper proposes a 21 point unifying
      hypothesis on the etiology and treatment of the disease. This hypothesis makes a
      series of assumptions, many of which are unproven, and is presented as a
      framework from which to investigate and treat the disease, not as a established
      biology. It is hypothesized that the underlying pathogenesis of MS is related to
      an inappropriate class of immune response against myelin antigens favoring
      proinflammatory Th1 versus anti-inflammatory Th2 or Th3 type responses.
      Environmental and genetic factors predispose toward MS by affecting the class of
      response and effectiveness of treatment is also related to how it impacts on this
      common final pathway. Because of epitope spreading, there is not one autoantigen
      involved in MS and the progressive form of MS differs immunologically from the
      relapsing remitting form. Viruses trigger and perpetuate MS, although MS is not
      related to a persistent viral infection. Because MS is a multifactorial disease,
      there are clinical and perhaps immunological subtypes of MS and a single type of
      treatment is unlikely to control the disease in all patients. Thus, there will be
      responders and non-responders to each effective therapy and ultimately
      combination therapy will be required to cure the disease.

PMID- 9604130
TI  - Ischemic neuronal injury is ameliorated by astrocyte activation.
AB  - BACKGROUND: The motivation of this study was to more precisely define the in vivo
      role of astrocytes in forebrain ischemia. Controversy exists in the literature as
      to whether they protect or injure neurons in this setting. METHODS: Astrocytes in
      the rat hippocampus were disabled with stereotactic administration of a
      gliotoxin, ethidium bromide, 3 days prior to induction of forebrain ischemia. The
      extent of neuronal injury in this group was compared to a control category
      receiving intrahippocampal saline only. RESULTS: Saline-injected animals
      demonstrated decreased hippocampal CA1 sector injury, and increased gliosis on
      the side of the injection compared to the contralateral side (P < 0.01) or
      ethidium bromide-treated animals (P < 0.05). CONCLUSIONS: The results suggest
      that activated astrocytes are protective to neurons subjected to an ischemic
      insult. This may result from their ability to elaborate neurotrophic factors,
      buffer potassium and metabolize a variety of neurotransmitters.

PMID- 9604131
TI  - The course of post-traumatic amnesia: three little words.
AB  - OBJECTIVE: To provide a simple means of "real time" recognition of emergence from
      post-traumatic amnesia (PTA). METHODS: Ninety-one patients with traumatic brain
      injury (PBI); 53 minor (GCS 13-15), 19 moderate (GCS 9-12), 18 severe (GCS 3-8).
      Twenty-seven control subjects treated at two regional trauma units for their
      acute phase and followed in a hospital-based research institute were studied
      prospectively. Subjects were examined repeatedly following injury with the
      Galveston Orientation and Amnesia Test (GOAT) and tests of their ability to learn
      and retain new information. Word triplets balanced for concreteness and frequency
      were presented. Immediate and 24-hour recall were tested. If 24-hour recall was
      imperfect, recognition was tested by presenting the 3 target words and 6
      distracters. The target words were then re-presented and recall was tested the
      next day. The time intervals to first perfect recognition and first free perfect
      recall were compared with the patients' first GOAT score of 75 or greater on 2
      successive days. Simple line drawings of common objects were also presented to
      the subjects using an identical paradigm. The outcome measures were GOAT, 3-word
      recognition and recall, 3 picture recognition and recall. RESULTS: For all
      categories of head injury severity, the median interval to perfect free recall of
      words followed the achievement GOAT criterion by a significant interval. The mean
      GOAT scores for perfect 3-word recall and recognition corresponding to minor,
      moderate and severe injuries were 97, 90 and 88, and 97, 76 and 68 respectively.
      The recognition and recall of pictures preceded the recognition and recall of
      words by approximately 1 day. CONCLUSIONS: The orientation measures of the GOAT
      that contain material that the patient knew prior to injury obscure the
      determination of recovery of continuous memory and should be tested separately.
      Three-word recall which is simpler to administer than the GOAT is a more reliable
      measure of emergence from PTA. For patients who are dysphasic or who do not share
      a common language with the examiner, 3-picture recognition and recall may
      substitute for word recognition and recall.

PMID- 9604132
TI  - Prevalence of cerebral palsy in Alberta.
AB  - BACKGROUND: In spite of scattered reports to the contrary, concern is continually
      expressed that the frequency of cerebral palsy has not decreased with modern
      perinatal/neonatal care. Overall, epidemiological information on cerebral palsy
      is scant. The generally accepted prevalence is 2 to 2.5 per thousand school-age
      children. METHODS: A population-based record linkage study of a presently living
      cohort of 96,359 children born from April, 1985 through March, 1988 and followed
      over an eight-year tracking period captured the diagnostic codes for all fee-for
      service physician claims, all hospital separations and individual birth data from
      the Department of Vital Statistics of the Government of Alberta. The ICD-9 code
      "343" was used to identify subjects. The childhood prevalence and frequency by
      birthweight-specific sub-groups of cerebral palsy after age three years
      (congenital, 229 [92.3%]; probable acquired 19 [7.7%]) were identified giving an
      overall prevalence of 2.57 per 1000. Seventy percent were diagnosed before their
      third birthday. Cohort prevalence of cerebral palsy for low birthweight children
      (< 2500 grams) was 17.7, very low birthweight (< 1500 grams), 78.5; and extremely
      low birthweight (< 1000 grams), 98.4. Low birthweight children made up just over
      one-third of cases in this study. CONCLUSIONS: Cerebral palsy continues to affect
      a significant number of children suggesting the prevalence of cerebral palsy has
      not decreased. The proportion of affected children with low birthweight in this
      study is less than that reported in the literature.

PMID- 9604133
TI  - Epidemiology and direct economic impact of hydrocephalus: a community based
      study.
AB  - BACKGROUND: The cost of care for hydrocephalic patients is not well established.
      METHODS: This retrospective study for the years 1990-1996 analyzed the cost of
      surgical intervention and hospitalization of hydrocephalic patients in the
      community-based setting of Manitoba, Canada, with a stable population of 1.138
      million. RESULTS: The number of discharges with a primary diagnosis of
      hydrocephalus was greater than 200 annually. The mean duration of hospital stay
      was 12.4 to 21.9 days, depending on the etiology of hydrocephalus. Approximately
      80 shunt procedures were performed annually. The total annual cost of care,
      excluding outpatient costs and chronic non-hospital based costs which could not
      be determined accurately, was estimated to be CDN$ 3.5 million in this community.
      CONCLUSIONS: Hydrocephalus is a chronic condition which puts substantial monetary
      demands on society and therefore deserves greater attention.

PMID- 9604134
TI  - A case-referent study of extrapyramidal signs (preparkinsonism) in rural
      communities of Israel.
AB  - BACKGROUND: In previous studies we reported an increased prevalence of
      Parkinson's disease in several kibbutzim of Southern Israel (cluster kibbutzim).
      Subsequent studies revealed a significant prevalence of subjects presenting
      extrapyramidal signs (preparkinsonism) in the same kibbutzim. On follow-up
      worsening of these signs was observed in some of the older subjects, some of them
      actually being diagnosed as suffering from 1-Dopa responsive Parkinson's disease.
      The current study was designed to evaluate possible etiologic factors for the
      development of preparkinsonism. METHODS: 317 subjects over the age of 40, living
      in five kibbutzim were examined and interviewed. 95 subjects presenting
      extrapyramidal signs were compared with 95 control subjects. They were matched
      for age, sex and length of residence in the kibbutz. Odds ratios were computed to
      identify exposure variables for logistic regression analyses. Detectors for
      carbamates and organic phosphates were applied at different sites of these
      kibbutzim. RESULTS: The severity and frequency of the extrapyramidal signs were
      higher in the older age groups, more in the "cluster", than in other kibbutzim. A
      very strong association was found between field crop work exposure, particularly
      cotton, and preparkinsonism (p = 0.0007) and a slightly weaker association for
      landscape work. The detectors picked up abundant pesticide traces (carbamates and
      organic phosphates) in the residential areas fairly distant from sites of aerial
      spray. CONCLUSIONS: We assume a chronic passive exposure of the residents in
      these kibbutzim to pesticides, in addition to any occupational exposures.

PMID- 9604136
TI  - Episodic cluster headache in a community: clinical features and treatment.
AB  - OBJECTIVE: To study the clinical features and treatment given to episodic cluster
      headache patients in the Calgary region. PATIENTS: Fifty-one (51) patients who
      responded to a media campaign, had previously been diagnosed by their family
      physicians, and who met International Headache Society (IHS) criteria for
      episodic cluster headache, formed the population for this study. METHODS: The
      media campaign consisted of newspaper advertisements and radio publicity
      including physician interviews and talk shows. Patients were required to complete
      by 200-item questionnaire detailing clinical features and treatment of their
      cluster headache syndrome. Each patient was also interviewed by our research
      nurse for clarification and proper completion of questionnaire. RESULTS: Fifty
      one percent (51%) of our patients had short headache attacks lasting one hour or
      less. Almost one-half (45%) had three or four attacks per 24 hour period. Eighty
      six percent (86%) had been referred to a neurologist. Sixty-nine percent (69%)
      had never used oxygen, but of those who had, one-half were still using it.
      Sumatriptan by injection had been tried by 26% of patients and of these, 93%
      considered it effective. Subcutaneous dihydroergotamine had been tried by 8%. For
      prophylaxis, 41% had tried methysergide, 31% prednisone, and 4% verapamil. Many
      patients had been prescribed migraine prophylactic drugs which are ineffective
      for cluster headache, and some had also undergone dental procedures or nasal and
      sinus surgeries. CONCLUSIONS: Many cluster headache patients had not, to their
      knowledge, been prescribed or used the best symptomatic and prophylactic
      treatments for cluster headache. This should be addressed through educational
      programs and through making up-to-date information on the treatment of cluster
      headache readily available to physicians and patients.

PMID- 9604135
TI  - Outcome evaluation of gabapentin as add-on therapy for partial seizures. "NEON"
      Study Investigators Group. Neurontin Evaluation of Outcomes in Neurological
      Practice.
AB  - OBJECTIVE: The safety, tolerability, efficacy, and impact on quality of life of
      gabapentin (Neurontin) as adjunctive therapy to carbamazepine (CBZ) and/or
      phenytoin (PHT) was assessed in epileptic patients with partial seizures.
      METHODS: NEON (Neurontin Evaluation of Outcomes in Neurological Practice) was an
      open-label, prospective, multicentre study conducted in patients on a stable dose
      of CBZ and/or PHT and experiencing an average of up to 4 complex partial seizures
      with or without secondary generalization per month, with no seizure-free months.
      The treatment lasted 20 weeks. Gabapentin was started at 400 mg/day and was
      individually titrated to effective tolerable dose up to 2400 mg/day. Quality of
      life was evaluated using the QOLIE-10 questionnaire. RESULTS: A total of 141
      patients were enrolled at 36 sites; 114 patients were evaluable for efficacy
      analyses. The mean maintenance dose of gabapentin was 1600 mg/day (range = 300
      3200). A decrease of 50% or more in frequency of complex partial + secondary
      generalized seizures was observed in 81 (71%) patients (p = 0.0001). Fifty two
      (46%) patients were seizure-free during the last 8 weeks of treatment. A
      significant improvement (p < 0.05) was observed in 5 of the 10 questions of the
      QOLIE-10, as well as in the composite QOL score (p = 0.0002). The most frequent
      adverse events included somnolence (16%), dizziness (9%), and asthenia (6%).
      Twenty-five (18%) patients prematurely discontinued the study, 16 (11%) of them
      due to adverse events. CONCLUSIONS: This study indicates that treatment with
      gabapentin as adjunctive therapy to standard antiepileptic drugs in this group of
      patients not only provides significant improvement in seizure control, but also
      has a positive impact on quality of life. The clinical benefits in efficacy,
      safety and tolerability demonstrated at 20 weeks are sustained, and no tolerance
      develops with gabapentin in longer term use.

PMID- 9604137
TI  - In-patient treatment of chronic daily headache using dihydroergotamine: a long
      term follow-up study.
AB  - BACKGROUND: The treatment of chronic daily headache (CDH) due to medication
      overuse remains a common and difficult problem. For selected patients refractory
      to outpatient management we have used a treatment protocol using
      dihydroergotamine (DHE) as introduced by Raskin, during a brief (typically 48
      hours) in-patient stay. While many studies have documented the short-term
      efficacy of the DHE protocol, there are limited data on its long-term effects.
      The purpose of this study was to evaluate quality of life, at three months post
      treatment and the present time. METHODS: A retrospective chart review of all
      patients admitted for the DHE protocol from 1991 to 1996 revealed 174 cases. Of
      these, 132 patients were interviewed by phone. RESULTS: The DHE protocol was
      shown to decrease headache frequency, severity, headache medication use, and
      absences from work both at three months and the time of interview. CONCLUSION:
      This study has the largest patient base and the longest follow-up period for the
      use of DHE for CDH. The results confirm that the DHE protocol is helpful in
      breaking the cycle of CDH, although the long-term outcomes of this study are more
      conservative than other studies have reported.

PMID- 9604138
TI  - Migraine-like symptoms triggered by occipital lobe seizures: response to
      sumatriptan.
AB  - BACKGROUND: The relationship of ictal and post-ictal cephalic pain to migraine
      remains debatable. We hereby report 2 patients, a 27-year-old woman and 41-year
      old man were referred for assessment of migraine of 10 years and 4 years
      duration, respectively. The man described a recent episode of "vacant stare" and
      the woman has sensitivity to bright colours and light. Neurological examination,
      visual field testing, CAT scan, MRI scan, and prolonged EEG recordings were
      accomplished for each patient. RESULTS: The man had a spontaneous seizure with
      ictal discharge arising from the right occipital lobe. Bilateral occipital
      spikes, associated with palinopsia was triggered in the woman by photic
      stimulation. Both patients developed post-ictal headaches with symptoms similar
      to their migraines. The symptoms subsided following treatment with oral
      sumatriptan. CONCLUSION: Migraine-like symptoms occurring following occipital
      lobe seizures may share similar pathophysiological substrates with idiopathic
      migraine. Serotonergic mechanisms may be implicated.

PMID- 9604139
TI  - Hydrocephalus: obliterated perimesencephalic cisterns and the danger of sudden
      death.
AB  - OBJECTIVE: We reported a possible risk factor which could identify patients with
      chronic hydrocephalus who are risk for sudden death. METHODS: A retrospective
      review of medical records and computed tomographic (CT) scans was conducted on
      three patients with chronic hydrocephalus who suffered acute cardiorespiratory
      arrest without those signs which are normally associated with a progressive
      worsening of hydrocephalus. RESULTS: All three of these patients were awake and
      communicative shortly before the life threatening or terminal event. All had
      experienced some recent worsening of neurologic signs or symptoms, but none had
      shown a progressive impairment of consciousness or major neurologic decline
      ordinarily associated with life threatening elevation of intracranial pressure.
      Absence of the perimesencephalic cisterns on head CT scans done prior to or just
      after the life threatening event was the only new radiologic finding common to
      all these patients. CONCLUSIONS: The absence of the perimesencephalic cisterns in
      an awake and alert patient with severe hydrocephalus indicates that the patient
      may be at risk for neurogenic cardiorespiratory failure. In such cases,
      (especially when there has been a recent, albeit mild, change in neurologic signs
      or symptoms), the neurologist should urge emergency ventriculostomy or shunting
      for the hydrocephalus.

PMID- 9604140
TI  - Conservative treatment of acute spontaneous spinal epidural hematoma.
AB  - BACKGROUND: In cases of acute spontaneous epidural hematoma producing
      neurological deficits, emergency surgical evacuation is the standard treatment.
      METHODS: Such a case is presented in which complete resolution of neurological
      deficits occurred without surgical intervention. RESULTS: This is the fifth
      reported case of complete recovery in a patient managed conservatively. In most
      reports, significant and sustained neurological recovery had occurred with 12
      hours of impairment of walking. CONCLUSION: In cases of acute spontaneous spiral
      epidural hematoma in which neurological deterioration is followed by early and
      sustained recovery, non-operative therapy may be considered.

PMID- 9604141
TI  - Hemorrhagic necrotic schwannoma presenting as purulent meningitis.
AB  - BACKGROUND: Intracranial schwannoma involving the XIIth cranial nerve is rare. We
      report an unusual clinical presentation and pathological verification of a
      schwannoma, which had become haemorrhagic and necrotic, simulating acute purulent
      meningitis. METHODS: A literature review of intracranial tumors presenting as
      acute purulent meningitis, with emphasis on schwannomas, was undertaken. RESULTS:
      Few cases of hypoglossal schwannoma have been reported; the association with
      purulent meningitis has not been previously documented. CONCLUSION: In patients
      presenting with sterile purulent meningitis, a necrotic tumor should be
      considered as a possible etiology.

PMID- 9604142
TI  - Congenital entrapment of the lateral cutaneous nerve of the calf presenting as a
      personal sensory neuropathy.
AB  - OBJECTIVE: Presentation of an unusual case of congenital entrapment of the
      lateral cutaneous nerve of the calf (LCNC) mimicking a peroneal sensory
      neuropathy. METHODS: We report the case of as 16-year-old girl with a 3 year
      history of progressive tingling, numbness and pain in her right calf precipitated
      by athletic activities involving repeated flexion and extension of the knee. A
      Tinel's sign was present over the common peroneal nerve in the distal popliteal
      fossa but absent at the fibular neck. Motor and sensory examination of the common
      peroneal nerve was normal as were electrophysiological studies and MRI. RESULTS:
      At surgery, the LCNC, a sensory branch of the common peroneal nerve, was
      entrapped at a point where it pierced the tendon of the biceps femoris muscle.
      Transection of the part of the tendon overlying the LCNC resulted in complete and
      permanent relief of symptoms. SIGNIFICANCE AND CONCLUSION: The proximal location
      of the Tinel's sign, absence of motor or sensory deficits and normal
      electrophysiology suggested, preoperatively, that this was not an entrapment of
      the common peroneal nerve at the fibular neck but rather a more proximal
      abnormality likely involving only a part of the peroneal nerve or one of its
      sensory branches. As a result, the more proximal exposure of the peroneal nerve
      within the popliteal fossa revealed entrapment of the neuropathy of the common
      peroneal nerve or one of its branches, due to a normal nerve piercing an
      otherwise normal tendon. Secondly, there are no previously reported cases of
      surgically documented compression of the LCNC in an otherwise normal patient
      (i.e. non-diabetic).

PMID- 9604143
TI  - Pharmacokinetics of KW-4679 in the elderly: single-dose and multiple-dose trials.
AB  - We evaluated the pharmacokinetics of KW-4679, a new antiallergic agent, in the
      elderly in trials of both single and multiple dosing. In the single-dose trial,
      the pharmacokinetics of a single dose of 10 mg KW-4679 in elderly male subjects
      was compared with those in young male subjects. In the multiple-dose trial
      lasting 6 consecutive days with elderly male subjects, the pharmacokinetics of
      the last dose of 10 mg KW-4679 were compared with those of the first dose to
      evaluate the accumulation of KW-4679 and/or its metabolites. In the single-dose
      trial, the maximum concentration and the area under the concentration time curve
      of KW-4679 in the elderly subjects were significantly greater than those in the
      young subjects, while the apparent total body clearance was significantly lower
      in the elderly subjects. There was no significant difference in the fraction of
      KW-4679 excreted in the urine between the elderly and the young subjects. The
      renal clearance of KW-4679 in the elderly subjects was significantly lower than
      that in the young subjects. Although the renal clearance was correlated with the
      creatinine clearance, the renal clearance was significantly greater than the
      creatinine clearance, suggesting that this agent undergoes renal tubular
      secretion. In the multiple-dose trial, all pharmacokinetic parameters examined,
      except the maximum concentration, showed no difference between the first and the
      last administration. No accumulation of KW-4679 or its metabolites could be
      detected in the elderly subjects examined in the 6-day multiple-dose trial,
      though the present results suggest the dose should be reduced in the elderly
      subjects who have lower creatinine clearance.

PMID- 9604144
TI  - Multicenter trial comparing tramadol and morphine for pain after abdominal
      surgery.
AB  - Seventy patients (40 male, 30 female), mean (SD) age 60.8 +/- 13.7 years were
      treated with parenteral morphine (10 mg/1 ml ampul) or tramadol (100 mg/2 ml
      ampul) to verify their analgesic effects in pain following abdominal surgery. The
      multicenter trial followed an open, controlled experimental design between
      patients, randomized within the centers. The drugs were given by intramuscular
      injection, as requested by patients, starting in the postoperative period when
      pain was more than 70 mm, assessed on a visual analog scale. Patients were
      allowed up to six ampuls of tramadol or morphine in the 24-h trial but in the
      first 4 h, if they asked for supplementary analgesic, only diclofenac (75 mg in a
      3-ml ampul) was allowed. Both test drugs gave rapid and constant pain relief.
      After the first dose, pain intensity was reduced 36.2% with tramadol, and 51%
      with morphine; the pain-free interval was similar for both treatments. The
      quality of sleep and the number of hours of sleep the night after surgery were
      similar for both groups. Tramadol was tolerated better, giving rise to no
      untoward reactions; with morphine there was one case of mild respiratory
      depression. In abdominal surgery, therefore, tramadol given by intramuscular
      injection has postoperative analgesic activity similar to morphine, but is better
      tolerated.

PMID- 9604145
TI  - Inhibition by nimesulide of prostaglandin production in rat macrophages.
AB  - We have investigated the inhibitory action of nimesulide (4-nitro-2
      phenoxymethanesulfonanilide) on release of prostaglandin E2 (PGE2) from rat
      peritoneal exudated macrophages (macrophages) and its mechanism of action. PGE2
      release from macrophages stimulated with opsonized zymosan (OPZ) were increased
      in the 20 h after stimulation, whereas no significant increase was noted in PGE2
      release from unstimulated macrophages. Nimesulide caused a weak inhibition of
      PGE2 release from macrophages at 15 min after OPZ stimulation as compared with
      indomethacin, but nimesulide caused approximately the same strong inhibition as
      indomethacin at 10 h after OPZ stimulation. Cellular cyclooxygenase (COX)
      activity in macrophage at 10 h after OPZ stimulation was increased approximately
      seven times the COX activity in macrophages before OPZ stimulation. Nimesulide
      caused approximately the same strong inhibition of cellular COX activity as
      indomethacin at 10 h after OPZ stimulation. COX-1 mRNA was expressed in
      macrophages irrespective of OPZ stimulation, but COX-2 mRNA was expressed only
      after OPZ stimulation, and COX-2 protein was simultaneously induced. Nimesulide
      affected neither the levels of COX-1 mRNA and COX-2 mRNA at 4 h after OPZ
      stimulation nor the levels of COX-2 protein at 10 h after OPZ stimulation. In
      contrast, actinomycin D caused strong inhibition of COX-2 mRNA expression and
      protein induction. These results suggest that inhibition by nimesulide of PGE2
      release from macrophages, namely inflammatory cells, would be neither due to
      inhibition of COX-2 mRNA expression nor COX-2 induction, but to the selective
      inhibition of COX-2 activity itself.

PMID- 9604146
TI  - Effect of magnesium pyridoxal 5-phosphate glutamate on vascular reactivity in
      experimental hypercholesterolemia.
AB  - Hypercholesterolemia is known to affect the responsiveness of various blood
      vessels to endogenous and to exogenous vasoactive agents. Of particular interest
      is the increased responsiveness to vasoconstrictors, e.g., 5-hydroxy tryptamine
      and noradrenaline, and the decreased reactivity towards vasodilators, e.g.,
      acetylcholine. This, together with the development of arteriosclerosis, could
      play an important role in the progression of many vascular complications, such as
      hypertension and coronary heart disease. Magnesium pyridoxal 5-phosphate
      glutamate (MPPG) has been shown to effectively reduce serum lipids in animals and
      in man, and to retard the progression of atherosclerotic lesions in experimental
      animals. It was therefore considered of interest to investigate the reactivity of
      both the aorta and the renal artery to different vasoactive substances in
      hypercholesterolemic rabbits under the influence of MPPG as well as the effect of
      such substances on the blood pressure of the anesthetized animals. The rabbits
      were fed a high cholesterol diet for 2 months, followed by MPPG for 1 month,
      while keeping the rabbits on the same diet. One batch of animals was used for
      blood pressure recording and testing drug effects, and another was used for
      testing the responsiveness of their aortae and renal arteries to the different
      mediators. In hypercholesterolemic rabbits, treatment with MPPG tended to
      normalize the increased responsiveness of the blood pressure to the
      vasoconstrictors: noradrenaline and angiotensin and the diminished sensitivity to
      histamine and acetylcholine. For the isolated arteries, however, MPPG did not
      significantly affect the responses to noradrenaline nor potassium chloride, but
      tended to normalize responses to clonidine and acetylcholine. It could be
      concluded from the present findings that the high cholesterol diet induces
      changes in vascular reactivity which are possibly related to endothelial and/or
      receptor sensitivity changes. Treatment with MPPG helps to reverse these changes
      and to restore normal vascular reactivity, a fact that could have important
      clinical implications in the management of cardiovascular diseases.

PMID- 9604147
TI  - The possible "chondroprotective" effect of the unsaponifiable constituents of
      avocado and soya in vivo.
AB  - An experimental in vivo model for studying cartilage destruction has been used to
      study the possible chondroprotective effect of the unsaponifiable constituents of
      avocado, soya and their combination at a ratio of 1:2. The method consists of
      implanting rat articular cartilage wrapped in cotton subcutaneously in mice,
      treating the animals daily for 2 weeks with the preparations in question, then
      sacrificing the animals and measuring some biochemical parameters related to
      cartilage integrity. The chosen parameters involved the glycosaminoglycan and
      hydroxyproline content of the cartilage, as well as the hydroxyproline content of
      beta-D-glucosaminidase activity of the granulomatous tissue induced by the cotton
      covering the cartilage. The unsaponifiables of both avocado and soya
      significantly reduced the degenerative changes induced by the granuloma tissue on
      the implanted cartilage in control animals as reflected by the preservation of
      the glycosaminoglycan and hydroxyproline content, and also reduced the
      proliferation of hydroxyproline and beta-D-glucosaminidase activity of the
      granulomatous tissue. The effect was even more marked when animals were treated
      with the combination of the two unsaponifiables at a 1:2 ratio. The preservation
      of the cartilage from destruction may have been associated with a diminished
      release of inflammatory mediators due to the effects of the unsaponifiables. In
      this context, the results point to a possible "chondroprotective" effect of these
      agents in vivo. This is in keeping with previous reports of chondroprotection by
      these unsaponifiables in vitro. The effect of the fixed dose combination in the
      1:2 ratio was dose dependent.

PMID- 9604148
TI  - Evaluation of kinetic parameters of natural phytoalexin in resveratrol orally
      administered in wine to rats.
AB  - In view of the increasing interest in the biological activity of resveratrol, one
      of the components of red wine which is considered to be one of the main
      ingredients responsible for the beneficial effect of wine on human health, we
      have studied plasma kinetics and tissue bioavailability of this compound after
      red wine oral administration in rats. Plasma pharmacokinetics after oral
      administration of resveratrol could be described by an open one- or two
      compartment model. Tissue concentrations show a significant cardiac
      bioavailability, and a strong affinity for the liver and kidneys.

PMID- 9604149
TI  - The evolution of the distal radio-ulnar joint.
AB  - The pectoral girdle and the distal radio-ulnar joint have evolved over a period
      of 400 million years. Clinical circumstances exist that may represent atavistic
      development in modern man. Current understanding of this complex area does not
      explain all clinical situations.

PMID- 9604150
TI  - Osseous anatomy and articular relationships about the distal ulna.
AB  - The distal radio-ulnar joint (DRUJ) has a bony anatomy that contributes very
      little to stability. This article discusses the osseous anatomy about the distal
      end of the ulna. The structures that support the stability of the DRUJ, such as
      the triangular fibrocartilage complex, the tendon sheath of the extensor carpi
      ulnaris, the pronator quadratus muscle, and other tendons on the ulnar side of
      the wrist are reviewed.

PMID- 9604151
TI  - Soft-tissue anatomy and relationships about the distal ulna.
AB  - The author investigates the complex anatomic relationship between the ulnar head
      and adjacent osseous structures (radius and carpus). Special attention is
      directed to the orientation and shape of the articular surfaces the constraining
      effects of specific membranes and ligaments (radio-ulnar and ulnocarpal), the
      shock-absorbing function of the triangular fibrocartilage, and the dynamic action
      of specific muscles (pronator quadratus and extensor carpi ulnaris) The anatomy
      of other nonstabilizing structures (meniscus homologue and prestyloid recess) is
      also discussed.

PMID- 9604152
TI  - Clinical examination of the distal ulna and surrounding structures.
AB  - A complete understand of the anatomy of the ulnar aspect of the wrist and the
      potential pathologies that may afflict it is the key to making an accurate
      diagnosis, ordering appropriate ancillary studies, and providing comprehensive
      patient management for problems in the region. This article focuses on the
      clinical examination of the skeletal, articular, and soft-tissue components about
      the distal ulna. Differentiation of distal ulnar maladies from more proximal
      conditions producing ulnar wrist symptoms is also reviewed.

PMID- 9604153
TI  - Imaging modalities for study of the distal ulnar region.
AB  - Judicious use of diagnostic imaging maximizes the diagnostic capabilities of the
      surgeon treating the distal radio-ulnar joint (DRUJ). A good clinical history and
      clinical examination are necessary to direct the selection of appropriate imaging
      studies. Plain radiographs are almost always the first imaging examination. More
      advanced imaging techniques are costly and may provide only limited information.
      This article discusses imaging modalities useful for assessment of the DRUJ and
      the area around it.

PMID- 9604154
TI  - The management of acute fractures involving the distal radio-ulnar joint and
      distal ulna.
AB  - The acute management of fractures involving the distal radio-ulnar joint and
      distal ulna is controversial. The primary goal is recognition and differentiation
      between stable and unstable fracture patterns. Although an operative approach is
      adopted in the treatment of these injuries, the optimal management protocol
      awaits good prospective randomized studies.

PMID- 9604155
TI  - Injuries about the distal ulna in children.
AB  - This article examines several types of injuries about the distal ulna that appear
      in children. Ulnar styloid fractures are relatively common and tend not to have
      the deforming potential of Salter-Harris-type injuries. Physeal injuries with
      their potential for long-term growth impairment and functional limitation are
      potentially the most serious. Chronic stress injuries at the distal ulna, as seen
      in competitive gymnasts, and chronic late disruption of the distal radio-ulnar
      joint are also discussed.

PMID- 9604156
TI  - A systematic approach to handling the distal radio-ulnar joint in cases of
      malunited distal radius fractures.
AB  - The distal radio-ulnar joint (DRUJ) is often the site of persistent symptoms
      after malunion of distal radius fractures. These malunions alter load transfer
      across the ulnocarpal joint, disturb DRUJ kinematics, and result in joint
      incongruity at the sigmoid notch. Treatment of distal radius malunions must not
      only correct position of the radial platform and joint incongruity but also
      restore anatomic relationship at the DRUJ. A systematic approach to the surgical
      reconstruction of these multiplanar deformities using clinical and radiographic
      parameters is outlined.

PMID- 9604157
TI  - Ulnocarpal abutment. Treatment options.
AB  - Ulnocarpal abutment presents a significant clinical challenge. In the last two
      decades, the anatomy of the ulnar side of the wrist and the pathophysiology of
      ulnocarpal abutment have been defined more clearly. Based on this greater
      understanding, a variety of treatments have been devised. This article reviews
      the current methods of treatment of ulnocarpal abutment.

PMID- 9604158
TI  - The indications for and techniques and outcomes of ablative procedures of the
      distal ulna. The Darrach resection, hemiresection, matched resection, and Sauve
      Kapandji procedure.
AB  - Several ablative procedures exist for the treatment of distal radio-ulnar joint
      arthritis. This article describes the indications, techniques, pitfalls, and
      outcomes for the four most popular procedures: Darrach, hemiresection
      interposition, Sauve-Kapandji, and matched ulnar resection. The authors explain
      their personal algorithm for treatment selection, emphasizing patient
      requirements versus the physiologic characteristics of each procedure.

PMID- 9604159
TI  - Salvage procedures after failed surgery about the distal ulna.
AB  - This article discusses four types of salvage procedures that may offer a
      successful means of treating patients after failed distal ulnar surgery. The
      procedures include distal radio-ulnar joint fusion, the Sauve-Kapandji procedure,
      creation of a one-bone forearm, and massive resection of the distal ulna.

PMID- 9604160
TI  - The role of operative arthroscopy for the diagnosis and treatment of lesions
      about the distal ulna.
AB  - Operative arthroscopy of the wrist compliments the physical examination and
      radiographic imaging to improve diagnosis and treatment of lesions about the
      distal ulna. This article reviews the relevant anatomy, biomechanics, and
      classification of acute and degenerative lesions of the triangular fibrocartilage
      complex (TFCC). Minimally invasive diagnostic and management techniques for TFCC
      tears are described in detail.

PMID- 9604161
TI  - Treatment of acute and chronic instability of the distal radio-ulnar joint.
AB  - This article discusses the joint mechanics and the anatomy of the forearm with
      respect to understanding instability of the distal radio-ulnar joint. Acute and
      chronic instability are reviewed, and treatments are discussed.

PMID- 9604162
TI  - Disorders of the forearm axis.
AB  - Forearm pronosupination is a complex, integrated activity that demands
      specialized function of all structures between the elbow and wrist. This article
      describes the forearm axis as a comprehensive concept to unify these
      relationships. The anatomy and biomechanics of the forearm axis are reviewed.
      Pathologies that affect the entire axis are summarized.

PMID- 9604163
TI  - Inflammatory and traumatic tendinopathies about the ulnar wrist.
AB  - Tendinopathy about the ulnar aspect of the wrist may involve either extensor or
      flexor structures and has a variety of causes. Although relatively less common
      than intra-articular pathology, disorders of these superficial structures must
      not be neglected when performing a physical examination of the ulnar wrist or
      developing a differential diagnosis for patients with ulnar wrist pain.

PMID- 9604164
TI  - Brief communication: a software solution for reducing startle eyeblink responses.
AB  - We examined the viability of a software-based spectral method for reducing
      acoustic startle eyeblink responses. Fifteen young adults were presented with a
      95 dB burst of white noise for 50 ms while they viewed slides that varied in
      affective valence. The startle EMG responses were analyzed using a discrete
      Fourier transform software-based spectral method. A significant linear trend was
      found between slide valence and startle amplitude, replicating previous work.
      Subjects' startle responses became more augmented as the content of the slides
      became more unpleasant. The advantages of software-based solutions for reducing
      startle EMG responses are discussed.

PMID- 9604165
TI  - The development of interlimb coordination during bimanual finger tapping.
AB  - Normal subjects aged 7-25 years were asked to tap the index fingers of both
      hands: a) in four different patterns of interlimb coordination; b) at two
      different response frequencies; and c) both before and after the entraining
      metronome was turned off. The outcome variables of primary interest were the
      within-subject variability of interresponse intervals (IRI) as an index of timing
      precision; and deviations from prescribed response frequency, as an index of
      temporal tracking accuracy. Stability of timing precision and accuracy of
      temporal tracking increased significantly from 7 to 9 and from 9 to 11 years,
      with only minor advances thereafter. There were significant right-left
      performance asymmetries in all bimanual tasks; variability of IRI and deviations
      from prescribed rate were greater at the faster of the two response frequencies
      tested; and stability of IRI and accuracy of temporal tracking were greater with
      than without the metronome. Stability of IRI and accuracy of temporal tracking
      were strongly correlated in some bimanual tasks. The findings are discussed in
      terms of the two major theoretical perspectives on human brain-behavior
      relationships that have specifically addressed the issue of bimanual
      coordination.

PMID- 9604166
TI  - Activity and passive-avoidance learning in cobalt-injected rats.
AB  - A wide range of cognitive-behavioral sequelae, including memory deficits, results
      from hard metal disease in humans. Cobalt is a common component in the
      manufacture of hard metals and is a biologically active, toxic substance. This
      study examined the effects of cobalt exposure in rats. Results showed decreased
      exploratory behavior and a trend for higher-dose subjects to show decreased
      passive avoidance learning. No significant differences in active maze learning
      were found. These results indicate the value of further explorations of the
      cognitive-behavioral effects of cobalt exposure and suggest a number of
      methodological cautions.

PMID- 9604167
TI  - Quantified EEG in patients with vertigo of central or peripheral origin.
AB  - Computerized EEG frequency analysis was performed in 18 patients with peripheral
      vestibular dysfunction (PVD), 17 patients with central vestibular dysfunction
      (CVD) and 22 aged matched controls. Increase in the relative theta activity in
      the centrotemporal region was found in patients with PVD. The decrease of
      centroparietal beta activity in both groups of patients, as compared to controls,
      did not reach statistical significance. We conclude that quantified EEG may be a
      sensitive method to show changes of cortical electrical activity in patients with
      vertigo, reflecting the imbalance in afferent vestibular input to the cortex.

PMID- 9604168
TI  - Reversal of a body image disorder (macrosomatognosia) in Parkinson's disease by
      treatment with AC pulsed electromagnetic fields.
AB  - Macrosomatognosia refers to a disorder of the body image in which the patient
      perceives a part or parts of his body as disproportionately large.
      Macrosomatognosia has been associated with lesions in the parietal lobe,
      particularly the right parietal lobe, which integrates perceptual-sensorimotor
      functions concerned with the body image. It has been observed most commonly in
      patients with paroxysmal cerebral disorders such as epilepsy and migraine. The
      Draw-a-Person-Test has been employed in neuropsychological testing to identify
      disorders of the body image. Three fully medicated elderly Parkinsonian patients
      who exhibited, on the Draw-a-Person Test, macrosomatognosia involving the upper
      limbs are presented. In these patients spontaneous drawing of the figure of a man
      demonstrated disproportionately large arms. Furthermore, it was observed that the
      arm affected by tremor or, in the case of bilateral tremor, the arm showing the
      most severe tremor showed the greatest abnormality. This association implies that
      dopaminergic mechanisms influence neuronal systems in the nondominant right
      parietal lobe which construct the body image. After receiving a course of
      treatments with AC pulsed electromagnetic fields (EMFs) in the picotesla flux
      density applied transcranially, these patients' drawings showed reversal of the
      macrosomatognosia. These findings demonstrate that transcranial applications of
      AC pulsed EMFs affect the neuronal systems involved in the construction of the
      human body image and additionally reverse disorders of the body image in
      Parkinsonism which are related to right parietal lobe dysfunction.

PMID- 9604169
TI  - Clinical role and mechanisms of action of analgesic nitrous oxide.
AB  - We give a brief history and development of the use of analgesic nitrous oxide in
      various clinical situations, emphasizing the very important difference between
      analgesic and anesthetic concentrations of the gas. We give evidence for the
      opioid nature of analgesic nitrous oxide and the probable role that these opioid
      properties play in its clinical effects. Its uniqueness among the opioids arises
      from its ability to safely stimulate both mu and kappa opioid receptors thereby
      modulating these systems, which are at times antagonistic to each other. These
      opposing systems appear to be particularly important during addictive withdrawal.
      We also discuss the possible relationship existing between nitric and nitrous
      oxide.

PMID- 9604170
TI  - The effects of cadmium and experimental diabetes on VEP spectral data and lipid
      peroxidation.
AB  - Fifty-two healthy swiss male albino rats, aged three months were used in this
      study. They were divided into four groups: Control (C), diabetic (D), Cadmium
      (Cd) and diabetic + Cadmium (D + Cd) groups. Diabetic condition was induced in D
      and D + Cd groups by administration of alloxane (5 mg/100 g). After this
      treatment, Cd and D + Cd groups were injected with CdCl2 i.p. (2 mg/kg/week). At
      the end of the two months of experimental period, flash visual evoked potentials
      (FVEPs) of four groups were recorded and amplitude spectral analysis was computed
      by transient response-frequency characteristics (TRFC) method. Significant
      amplitude decrement was found in 2-4 Hz frequency band of D + Cd group in
      comparison with C group. On the other hand, our data showed that Cd treatment and
      diabetic condition caused a significant increase of lipid peroxidation in kidney,
      brain, retina and lens.

PMID- 9604171
TI  - Fast and slow reaction time changes reflected in ERP brain function.
AB  - A number of studies have examined the average late component Event Related
      Potential (ERP) and Reaction Time (RT) in response to multiple target stimuli
      (across-trial averages). This study demonstrates within-trial differences in ERP
      brain function associated with relatively fast and slow RTs in 50 normal
      subjects. A conventional auditory oddball paradigm (with a 1 ISI) was employed.
      Increased ERP N100 and N200 amplitude (and decreased P200 amplitude), as well as
      earlier P200, N200 and P300 latency were found in the fast compared with the slow
      ERP subaverages. These results show the potential to elucidate temporal and
      spatial dynamics of brain function associated with changes in performance, in
      conventional "cognitive" paradigms applicable to both health and disease states.

PMID- 9604172
TI  - Different temporal stability and partial independence of EEG asymmetries from
      different locations: implications for laterality research.
AB  - In order to investigate a possible regional specificity of activation asymmetries
      of different parts of the cortex and the stability of these asymmetries across
      time and conditions, EEG was recorded during rest and stimulation conditions in a
      large sample of right-handed university students (n = 60). Recordings were made
      in two sessions (interval between sessions 2-4 weeks). In the first session two
      rest periods were conducted (interval 30 min) and one under stimulation. In the
      second session EEG was again recorded at rest. Reliability analyses show that the
      long-term stability of orbitofrontal asymmetries is markedly lower than that of
      dorsolateral, temporal, and parietal scores. Intercorrelations of EEG asymmetries
      at different electrode positions suggest that anterior and posterior EEG
      asymmetries are largely independent measures of cortical laterality. Both this
      partial independence of activation asymmetries and the differences in temporal
      stability underscore the significance of the anterior-posterior dimension in
      laterality research and may be one reason for several contradictory observations
      in studies on brain laterality.

PMID- 9604173
TI  - EEG alpha phase at stimulus onset significantly affects the amplitude of the P3
      ERP component.
AB  - Analysis of the relationship between prestimulus EEG alpha phase and the
      subsequent ERP has proved difficult because of the non-Euclidean nature of phase
      measurements. In this study, we employed a conventional P3 templating method of
      single-trial analysis to identify the P3 component in target auditory oddball
      data from 25 normals. As in previous studies, the absence or near absence of P3
      from a subset of single-trials was clearly demonstrated. We investigated this
      phenomenon to determine whether those single-trials with a large P3 had a
      different prestimulus alpha phase from those with a small or no P3. Statistical
      analysis of phase required the use of circular statistical analysis and the
      development of a new form of topographic mapping, circular topography. The alpha
      phase at stimulus onset in single-trials with a large P3 was significantly
      different from that in single-trials with a small or no P3 (p = .02).

PMID- 9604174
TI  - Functional perimetry combined with topographical VEP analysis.
AB  - The processing of visual input depends on the position of the visual stimuli in
      the visual field. Based on the anatomical structure of the retina and the cortex,
      the function and perception vary with the location in the visual field. Due to
      the low signal-to-noise ratio, electrophysiological recordings in human subjects
      commonly have to use large stimuli and, therefore, yield poor spatial resolution.
      The combination of the method of quasi-simultaneous stimulation of many small
      (1.5 degrees x 1.5 degrees squares) visual field elements by binary m-sequences
      and topographical recordings allowed us to reconstruct the potential maps
      elicited at each of 54 visual field locations independently. Twenty-two normal
      subjects participated in the experiments and observed monocularly a stimulation
      field of 13.5 degrees x 9 degrees filled with the 54 squares. Mean luminance was
      6.5 cd/m2 and contrast was 95%. The EEG was recorded in 30 channels with a dense
      array of electrodes over the occipital brain areas. Individual noise levels of
      the subjects were estimated and significant signals were analyzed quantitatively.
      We determined three components between 90 ms and 220 ms latency. Both global
      field power (GFP) and topography of the components were affected by retinal
      stimulus location, showing a significant decline of GFP with retinal
      eccentricity. Our data demonstrate that even small retinal targets may evoke
      brain activity which can be recorded simultaneously. Scalp field topography
      depends critically on the exact stimulus location within the foveal and
      parafoveal retinal areas while response strength mainly depends on eccentricity.

PMID- 9604175
TI  - QEEG assisted neuropsychological evaluation of autism.
AB  - The present case study utilizes neuropsychological procedures, quantitative
      electroencephalography (QEEG) and magnetic resonance imaging (MRI) to identify
      neural substrates of "autism" in a 25 year old Caucasian male. A priori
      hypotheses formed from a neuropsychological evaluation were supported by data
      from QEEG and MRI. Specifically, the neuropsychological evaluation was suggestive
      of left anterior deactivation and right frontal activation. Consistent with these
      results, QEEG data revealed relative activation of the right frontal region,
      while MRI results were suggestive of multiple small focal areas over the left
      frontal region and a teardrop shaped area of low attenuation across the right
      frontal region. The possible relation of right cerebral dysfunction and autism is
      discussed.

PMID- 9604176
TI  - Searching for the meaning of the Category Test and the Wisconsin Card Sort Test:
      a comparative analysis.
AB  - The Category Test (CT) and the Wisconsin Card Sort Test (WCST) have long been the
      major instruments used for the assessment of "frontal lobe" brain damage. These
      tests have often been used interchangeably by clinicians. However, research to
      date has disagreed on the extent to which these tests can be interpreted in a
      similar manner. The current paper examined the interrelationships between the
      tests in 112 mixed brain injured clients. The results showed relatively small
      correlations between the tests in the range of .4 to .6 which were eliminated
      when age, education, premorbid IQ (Vocabulary) and spatial skills (Block Design)
      were used as covariates. Regression analyses showed clear differences in which
      WAIS-R tests predicted each test, while factor analysis revealed little overlap
      between the tests except for a small relationship between the number of WCST
      categories completed and CT errors. The CT appeared to reflect spatial and
      spatial analysis skills while the WCST reflected verbal analysis and sequential
      skills. The results clearly indicate that the tests are not interchangeable and
      do not reflect the same underlying cognitive skills nor can they be interpreted
      in the same manner for neuropsychological purposes.

PMID- 9604177
TI  - Memory abilities during normal aging.
AB  - One hundred and five normal subjects from 20 to 89 years old, and with a minimum
      of six years of formal education were selected. Subjects were divided into seven
      age ranges, with 15 subjects in each group. The following tests were individually
      administered: (1) Wechsler Memory Scale (WMS) (Wechsler, 1945); (2) Serial Verbal
      Learning (Ardila, Rosselli & Puente, 1994; Ardila & Ostrosky, 1991); (3) The Rey
      Osterrieth Complex Figure (ROCF) (Osterrieth, 1944) (copy, immediate, and delayed
      reproduction); (4) Corsi's blocks (Milner, 1971) (forwards and backwards); and
      (5) Rivermead Behavioural Memory Test (Wilson, Cockburn, & Baddeley, 1985). This
      last test may be considered as a functional or ecological memory test. All test
      scores declined across ages between 4.1% and 76.6%. In all the tests, excepting
      Digits, standard deviations increased with age. It was observed that the youngest
      subjects could retain about three-fourths of the information presented, whereas
      the oldest retained around one-third of this information. About half of the test
      significantly correlated with the Rivermead Behavioral Memory Test. A factor
      analysis revealed four different factors accounting for 63.3% of the variance. A
      single nonverbal memory factor accounted for over 40% of the variance.

PMID- 9604178
TI  - Pelvic joint dysfunctions, lifting injuries, and testicular pain.

PMID- 9604179
TI  - Screening for carpal tunnel syndrome in the workplace.

PMID- 9604180
TI  - Occupational and environmental medicine competencies--v 1.0. The American College
      of Occupational and Environmental Medicine Panel to Define the Competencies of
      Occupational and Environmental Medicine.

PMID- 9604181
TI  - Cardiovascular disease morbidity in an Iowa law enforcement cohort, compared with
      the general Iowa population.
AB  - It remains uncertain if law enforcement officers experience an elevated
      cardiovascular disease morbidity and, if so, whether their profession contributes
      to this incidence. Consequently, the self-reported incidence of cardiovascular
      disease (CVD) (coronary heart disease, myocardial infarction, stroke, coronary
      artery bypass graft surgery, angioplasty) and CVD risk factors (age, diabetes,
      elevated body mass index (> or = 27.8 kg.m-2), hypercholesterolemia,
      hypertension, tobacco use) in 232 male retirees, > or = 55 years of age, from the
      Iowa Department of Public Safety were compared with 817 male Iowans of similar
      age. CVD incidence was higher in the law enforcement officers than the general
      population (31.5% vs 18.4%, P < 0.001). Using multiple logistic regression,
      factors found to be associated with CVD included the law enforcement profession
      (odds ratio [OR] = 2.34; 95% confidence interval [95% CI] = 1.5-3.6),
      hypercholesterolemia (OR = 2.37; 95% CI = 1.7-3.3); diabetes (OR = 2.22; 95% CI =
      1.4-3.6), hypertension (OR = 1.79; 95% CI = 1.3-2.5), tobacco use (OR = 1.67; 95%
      CI = 1.07-2.6), and age (OR = 1.06; 95% CI = 1.03-1.08). These results suggest
      that employment as a law enforcement officer is associated with an increased
      cardiovascular disease morbidity and this relationship persists after considering
      several conventional risk factors.

PMID- 9604182
TI  - Do psychological factors predict changes in musculoskeletal pain? A prospective,
      two-year follow-up study of a working population.
AB  - Our aim was to determine the predictive value of some psychometric instruments
      for the development and persistence of musculoskeletal pain. In 452 subjects,
      pain in the shoulder, neck, and low back during the preceding year was assessed
      at baseline, one year, and two years' follow-up. Psychological distress,
      depression, self-efficacy beliefs, subjective work prognosis, disability, and
      work characteristics were assessed at baseline. The best predictor of future pain
      was disability. The psychometric measures did not predict changes in pain. The
      explanatory power of the variables in the multivariate analyses was low.
      Perceived disability in persons with musculoskeletal symptoms should be
      acknowledged early. The traditional research paradigm focusing on a few
      hypothetically relevant variables does not take into account the reflective,
      dynamic, reciprocal nature of human behavior during the process of recovery from
      or development of a pain problem.

PMID- 9604183
TI  - Tumor necrosis factor-alpha and interleukin-8 release from U937 human mononuclear
      cells exposed to zinc oxide in vitro. Mechanistic implications for metal fume
      fever.
AB  - Respiratory exposure to zinc oxide results in metal fume fever, a flu-like
      illness characterized by dose-dependent increases in pulmonary tumor necrosis
      factor-alpha (TNF) and interleukin-8 (IL-8). To examine whether mononuclear cells
      are a source of these proinflammatory cytokines, we exposed U937 cells to zinc
      oxide in vitro. Cell culture supernatant TNF and IL-8 was measured after 3, 8,
      and 24 hours of exposure to zinc oxide in varying concentrations. Zinc oxide
      exposure in vitro led to TNF release in a dose-dependent manner at 3, 8, and 24
      hours (analysis of variance [ANOVA] P = 0.0001). IL-8 demonstrated a
      statistically significant zinc exposure response at 8 hours (ANOVA P = 0.005) and
      24 hours (ANOVA P = 0.02). IL-8 at 8 hours correlated with 3-hour TNF levels (r =
      0.52, P = 0.04). These data demonstrate that in vitro zinc oxide exposure
      stimulates U937 mononuclear cells to release TNF and IL-8 consistent with in vivo
      observations in metal fume fever.

PMID- 9604184
TI  - Chronic diffuse interstitial fibrosis of the lung in uranium miners.
AB  - Many uranium miners have been disabled by and died of pulmonary fibrosis that was
      not recognized as an occupational disease. A review of animal studies,
      complications from whole body irradiation, pulmonary function, and mortality
      studies of uranium miners led us to suspect radiation-induced chronic diffuse
      interstitial fibrosis in miners who had inhaled excessive radon progeny. A
      selected group of uranium miners (22) with severe respiratory disease (but no
      rounded nodules in chest films) were studied. Lung tissue from five disclosed
      severe diffuse interstitial fibrosis, with "honeycomb lung" in all. Some also had
      small anthrasilicotic nodules and birefringent crystals. Although quartz crystals
      probably contributed, we concluded that the predominant injurious agent in these
      cases was alpha particles from radon progeny. This disease, after a long latent
      period, usually results in pulmonary hypertension, shortness of breath, and death
      by cardiopulmonary failure.

PMID- 9604185
TI  - Medical surveillance for hematological disorders among active and retired oil
      refinery workers.
AB  - Ten-year (1985-1995) results of an expanded medical surveillance program of 2475
      active employees and retirees of an oil refinery and petrochemical complex in
      Illinois are presented. At the end of the program, 116 participants with
      persistent abnormalities of complete blood cell count had been referred for
      hematologic evaluation, and most were found to have benign conditions. Fifteen of
      the 116 were referred for bone marrow and cytogenetic studies. All of the
      referred active employees (seven) were found to have completely normal bone
      marrows with no evidence of any myelopathic process. Among the eight retirees,
      two had normal bone marrows, one was diagnosed with Philadelphia chromosome
      positive chronic myelogenous leukemia, one declined to participate, and four were
      diagnosed to have myelodysplastic syndrome (MDS) of various subtypes. A total of
      eight cases of MDS were identified, including six cases among program
      participants and two cases among nonparticipants. The MDS standardized incidence
      ratio of 1.26 (95% confidence interval = 0.54-2.47) was not statistically
      significant, and there was virtually no increase of MDS in persons less than 80
      years of age (4 observed and 3.8 expected). This MDS increase was entirely from
      program participants, probably because of intensive follow-up and diagnostic
      screening. Routine surveillance of complete blood cell count information did not
      identify any new cases of leukemia or MDS in active employees. These findings
      suggest that the utility of expanded medical surveillance program in this
      population is very limited.

PMID- 9604186
TI  - Long-term health and employment outcomes of occupational asthma and their
      determinants.
AB  - Occupational asthma is common, yet little is known about long-term outcomes in
      the United States. A case series of 55 (of 72) occupational asthma patients were
      interviewed in follow-up 31 (+/- 15) months after removal from the cause to
      evaluate asthma severity and employment outcomes. Standard criteria were used to
      rate severity. At follow-up, 54 subjects (98%) had active asthma, of which 26
      cases (47%) were "severe." Multivariate analysis showed increased risk of
      "severe" asthma for women (odds ratio [OR] = 13.8; 95% confidence interval [95%
      CI] = 1.3 to 151.7) and industrial sector workers (OR = 11.9; 95% CI = 1.3 to
      109.8). Thirty-eight subjects (69%) were unemployed, risk being greater for those
      with "severe" asthma (OR = 20.9; 95% CI = 1.9 to 229.8) and for those without a
      college degree (OR = 7.3; 95% CI = 1.2 to 43.4). These results indicate that
      occupational asthma is disabling and probably irreversible for most patients
      referred to a specialty clinic, despite prolonged removal from causative agents.
      Women, industrial workers, and those with severe asthma or lack of a college
      degree appear to be at risk for worse outcomes. Greater efforts at primary and
      secondary prevention should lessen the burden of long-term illness and
      unemployment due to occupational asthma.

PMID- 9604187
TI  - Elevation of zinc protoporphyrin levels in lead workers with iron-sufficient
      microcytosis.
AB  - Zinc protoporphyrin (ZPP) measurement is a required test under the Occupational
      Safety and Health Administration's lead standard. However, there is no mention of
      the influence of hemoglobinopathy on the ZPP test value. We undertook a
      retrospective laboratory review of 382 employees at the Argonne National
      Laboratory who had been subjects in a lead surveillance program since 1982. A
      total of 321 samples were analyzed, after female subjects and samples with
      abnormally high bilirubin levels were excluded. A group with low mean red blood
      cell volume (MCV; less than 80.0 fL) was compared with a group with normal MCV
      (greater or equal to 80.0 fL). A statistically significant difference was noted
      in ZPP (P < 0.007) and total bilirubin (P < 0.0003) values of two groups. There
      was no statistically significant difference noted in age, lead levels, or iron
      levels between the two groups. Abnormally high ZPP levels may occur in
      individuals with hemoglobinopathies. Only a minor part of this elevation could be
      explained by the higher bilirubin levels.

PMID- 9604188
TI  - Tuberculosis risk in funeral home employees.
AB  - In order to estimate the risk of tuberculosis infection among employees in the
      funeral service industry, we conducted a risk-assessment study of a convenience
      sample of funeral home employees. Study participants completed a risk-assessment
      questionnaire and underwent tuberculin skin testing. Of 864 employees tested, 101
      (11.7%) had a reactive tuberculin skin test. Reactivity to the tuberculin skin
      test was significantly associated with job category; funeral home employees with
      a present or past history of embalming deceased-human remains were twice as
      likely to be reactive as were non-embalming personnel (14.9% versus 7.2%, P <
      0.01). Reactivity was also associated with age, gender, race, past history of
      close contact with a person diagnosed with tuberculosis, and work history. After
      controlling for age and other factors, tuberculin reactivity was found to be
      associated in embalming personnel with the number of years spent performing
      embalmings (> or = 20), and, in non-embalming personnel, with a history of close
      contact with infected individuals. Based on these results, it is recommended that
      funeral home employees who routinely embalm cadavers undergo annual tuberculin
      skin testing, receive initial training on tuberculosis prevention, and wear
      respiratory protection when preparing known tuberculosis cases.

PMID- 9604189
TI  - Arthroscopic intra- and extra-articular anterior cruciate ligament reconstruction
      with gracilis and semitendinosus tendons.
AB  - Numerous surgical procedures have been developed and used for anterior cruciate
      ligament (ACL) reconstruction. Patellar tendon is probably the most common graft
      used, but gracilis and semitendinous tendons present some interesting advantages:
      small incision, large graft when doubled, characteristics close to ACL, rapid
      harvest. We describe a combined intra- and extra-articular arthroscopic ACL
      reconstruction using hamstring tendons which includes some original steps. The
      tendons are harvested, leaving the distal insertion intact, and sutured together.
      After drilling of the tibial tunnel, an over-the-top arrangement is formed,
      creating a groove in the posterolateral aspect of the femur. The tendons are then
      fixed with double staples in the groove, and their remaining part is fixed
      distally to Gerdy's tubercle passing under the fascia, but over the lateral
      collateral ligament (LCL). This technique ensures sufficient strength in the
      graft and permits correction of any associated instability, because of the
      presence of the extra-articular portion of the tendons. Furthermore, the over-the
      top arrangement reduces trauma and possible pitfalls related to tunnel
      construction and permits isometry of the extra-articular portion to be
      established. Forty patients involved in sports activity were prospectively
      selected and evaluated at a minimum 2 years' follow-up. IKDC score and Lysholm
      score were used for clinical evaluation, and the KT-2000 was used for
      instrumental laxity measurements. Resumption of sport and time to that point were
      recorded as well as Tegner activity score. We had 92.5% normal and fairly normal
      knees according to IKDC score and only 7.5% abnormal knees. Mean Lysholm score
      was 95. Mean Tegner score was 7.2. KT-2000 showed a mean injured/uninjured
      difference of 2.1 mm. In all, 90% of patients resumed sports at the same level,
      67.5% in 3-4 months and 27.5% in 4-6 months. The highly satisfactory results of
      this series with no major complications confirm the reliability of this technique
      and the possibility of guaranteeing functional behaviour in the knee.

PMID- 9604190
TI  - Double semitendinosus anterior cruciate ligament reconstruction: 10-year results.
AB  - In a series of 30 consecutive patients who suffered from chronic instability of
      the knee joint, reconstruction of the torn anterior cruciate ligament was
      performed with a looped semitendinosus tendon, reinforced by an extra-articular
      anterolateral procedure. Of these 30, 27 could be followed up 9-11 years after
      the operation. The evaluation included the International Knee Documentation
      Committee (IKDC) questionnaire and was completed by testing with a Kneelax
      arthrometer at 132 N and by anteroposterior standing X-ray, in order to evaluate
      the degenerative changes. At the time of the check-up: 96% of the study group
      considered that they had normal or nearly normal knees, and 81% had recovered to
      the same sports activity level as before their injury. The degenerative changes
      noted at the index operation did not progress notably, except in two cases.
      Laxities of 7 knees were normal, with a side-to-side difference of less than 2
      mm; 15 were nearly normal, with a mean difference of 3.45 mm; and 5 were
      abnormal, with a mean difference of 6.2 mm. The study shows that the procedure is
      efficient in restoring a satisfactory stability for most patients and stabilises
      the evolution of the degenerative lesions as shown by standing X-ray.

PMID- 9604191
TI  - Closing patellar tendon defects after anterior cruciate ligament reconstruction:
      absence of any benefit.
AB  - The most common graft in anterior cruciate ligament (ACL) surgery involves using
      the central one-third of the patellar tendon. Knowledge concerning the
      postoperative disability after harvesting the patellar tendon is, however,
      limited. The aim of this study was to evaluate the impact patellar tendon suture
      and bone grafting of the patellar bone defect might have in terms of functional
      outcome and patellofemoral pain after harvesting the bone-tendon-bone graft,
      compared with leaving the harvested site non-sutured and non-grafted. Sixty
      patients, scheduled for arthroscopically assisted ACL reconstruction, were
      randomly allocated to two groups. In group I, suture of the patellar tendon and
      bone grafting of the patellar defect were performed. In group II, the tendon gap
      and the patellar defect were left open. Preoperatively, there was no significant
      difference between the groups when comparing objective knee stability, as
      measured with a KT-1000 laxity meter, Lysholm score, Tegner activity level, IKDC
      score, or patello-femoral pain score. Both groups had a significantly improved
      Lysholm score at the 2-year follow-up, without any difference between them.
      Tegner's activity level was significantly lower at follow-up, compared with the
      pre-injury level in both groups. The patellofemoral pain score improved
      significantly after the reconstruction, without any difference between the
      groups. Ultrasonography did not reveal any difference between the groups in terms
      of healing of the tendon gap. This study revealed no differences in donor site
      morbidity, functional outcome, patellofemoral pain score or knee joint stability
      between the two treatment groups. The conclusion is that suture of the patellar
      tendon and bone grafting of the patellar defect do not improve the functional
      results or reduce donor site morbidity after arthroscopically assisted ACL.

PMID- 9604192
TI  - No benefit of bracing on the early outcome after anterior cruciate ligament
      reconstruction.
AB  - Forty patients were prospectively investigated to evaluate the effects of
      bandaging after reconstructive surgery of the anterior cruciate ligament (ACL).
      For the 6 weeks of the postoperative course, the operated knee was bandaged in 20
      patients (group A) and braced in the other 20 patients (group B). The isokinetic
      torque for extension and flexion (Cybex) and the range of motion (ROM) were
      investigated after 6, 12, 24 and 52 weeks postoperatively. At 24 weeks and 1 year
      postoperatively the stability of the knee joint (KT-1000) as well as the clinical
      outcome ('Orthopadische Arbeitsgemeinschaft Knie') were evaluated. No
      statistically significant differences between the two groups were found for the
      extension and flexion strengths. Free ROM was achieved significantly earlier in
      group A than in group B. No statistically significant differences regarding the
      stability of the operated knee joint nor the early outcome were found between the
      two groups. This study demonstrated that the renunciation of using a brace had no
      adverse effect on the early outcome with respect to stability and function. On
      the contrary, bracing seems not to be mandatory after ACL reconstruction when the
      central third of the patellar tendon is used.

PMID- 9604193
TI  - Articular cartilage homeostasis after anterior cruciate ligament reconstruction.
AB  - Several factors may be responsible for osteoarthritis after anterior cruciate
      ligament (ACL) reconstruction. The detrimental effect of the surgical technique
      may explain part of the progression of the pathologic process. In this study, the
      effect of ACL reconstruction on articular cartilage was investigated by measuring
      proteoglycan fragments (PF) in synovial fluid collected from patients who had
      undergone this operation. Synovial samples were obtained from 44 patients with
      chronic ACL deficiency aged 26 +/- 7 years preoperatively, and from some of them,
      samples were collected for monitoring at 1 month (n = 22), 3 months (n = 17), 6
      months (n = 18) and 12s month (n = 18). Synovial fluid taken from 12
      contralateral asymptomatic knees of 12 patients (not necessarily opposite knees
      of ACL-deficient cases) served as controls. Preoperative values were
      significantly larger than controls (P < 0.05). PF level reached its maximum value
      in the 1st month (P < 0.05) and then gradually decreased. It was significantly
      lower than preoperative values at 6 and 12 months but still greater than controls
      (P < 0.05). It seems that surgical trauma affects cartilage metabolism for the
      first 3 months postoperatively. Although reconstruction of the ACL contributes to
      articular cartilage homeostasis, a complete return to normal values cannot be
      achieved in 1st postoperative year at least in knees with chronic ACL deficiency.
      Long-term monitoring is needed to see whether these findings are early signs of
      osteoarthritis. Further studies may more clearly demonstrate the effect of the
      surgical procedure on knees with acute and subacute ACL deficiency.

PMID- 9604194
TI  - Interference screw fixation of hamstring vs patellar tendon grafts for anterior
      cruciate ligament reconstruction.
AB  - The present study was designed to investigate the fixation strength of a
      quadruple semitendinosus-gracilis graft compared with a middle-third bone
      patellar tendon-bone graft using a new interference screw developed to fix
      hamstrings grafts for ACL reconstructions (RCL Smith & Nephew Donjoy). Five pairs
      of human cadaveric knees from donors with a mean age of 43 (range 33-52) years
      were used. One knee of each pair was randomly allocated to be reconstructed on
      the femoral side with a semitendinosus-gracilis graft from the same donor using
      RCL screw fixation. As the control, the contralateral knee was correspondingly
      reconstructed with a bone-patellar tendon-bone graft using the same interference
      screw. The grafts were pulled out at a velocity of 30 mm/s by an axially applied
      load using a MTS machine. The mean (SD) failure load for the bone-patellar tendon
      bone graft fixations was 505 (25) N, 110% stronger than the mean failure load for
      the semitendinosus-gracilis graft fixations, which was 240 (47) N (P = 0.003).
      The stiffness for the patellar tendon-bone graft fixations was 46 (11) N/mm, 120%
      stiffer than the semitendinosus-gracilis graft fixations, which was 22 (11) N/mm
      (P = 0.01). This study shows that the interference screw principle used for ACL
      reconstructions with hamstrings tendons is inferior to that for bone-patellar
      tendon-bone reconstructions although the screw was developed especially for soft
      tissue fixation in bone tunnels.

PMID- 9604195
TI  - Primary reconstruction of the medial collateral ligament in combined injury of
      the medial collateral and anterior cruciate ligaments. Short-term results.
AB  - We describe our experiences with 22 patients who underwent acute surgical
      intervention for complete combined injury of the anterior cruciate ligament (ACL)
      and medial collateral ligament (MCL) in our hospital. In all patients, an
      arthroscopically guided repair of the MCL was performed, while the torn ACL was
      treated non-surgically. Primary reconstruction of the MCL in patients with
      complete disruptions of the MCL complex as well as the ACL reduces combined
      anteromedial instability to an isolated problem of the ACL. As a result of this
      treatment, the condition of 15 of 22 knees was improved, after an average
      duration of follow-up of 2 and a half years. In conclusion, our treatment
      strategy of an immediate repair of the MCL and reconstruction of the ACL when
      conservative treatment has failed seems safe and effective.

PMID- 9604196
TI  - Use of the International Knee Documentation Committee guidelines to assess
      outcome following anterior cruciate ligament reconstruction.
AB  - The purpose of this project was to determine if guidelines established by the
      International Knee Documentation Committee (IKDC) could distinguish differences
      in outcome, as indicated by the patients' subjective rating of knee function
      following ACL reconstruction, and to determine if all subgroups included in the
      IKDC rating system contribute to the prediction of the overall final IKDC rating.
      A total of 133 patients undergoing ACL reconstruction were evaluated according to
      IKDC guidelines 1-5 years postoperatively. Each subject was rated in each of four
      subgroups on the IKDC scale: patient subjective assessment, symptoms, range of
      motion (ROM), and laxity. The worst rating for the subgroups defined the overall
      final rating. The outcome from the patient's perspective was determined by asking
      them to rate the function of their knee on a scale from 0 to 100 with 100 being
      the level of function before injury. Average length of follow-up was 3.2 years
      (range 1.1-6.3 years). ANOVA indicated that the patients' subjective rating of
      knee function on a scale from 0 to 100 differed according to the overall final
      IKDC rating (F = 16.1, P < 0.001). The average subjective rating of knee function
      for those with a normal IKDC rating was 95.2, nearly normal was 91.2, abnormal
      was 84.9, and severely abnormal was 75.4. The average subjective rating of knee
      function for those who were severely abnormal was significantly different from
      those rated normal, nearly normal, and abnormal, and the average subjective
      rating for those who were abnormal was significantly different from those who
      were normal or nearly normal. There was no significant difference in average
      subjective rating between those who were rated as normal or nearly normal.
      Regression analysis indicated that all four subgroups contributed significantly
      to the prediction of the final IKDC rating (r2 = 0.70), but the majority of the
      variance (62%) was accounted for by symptoms and laxity. These results appear to
      indicate that the IKDC guidelines are useful for describing the outcome following
      ACL reconstruction. Further testing of the IKDC guidelines is necessary to
      determine if they are capable of detecting a change in the patients over time
      following treatment and/or surgery of the knee.

PMID- 9604197
TI  - Ligament force and joint motion in the intact ankle: a cadaveric study.
AB  - The aims of this study were to measure the forces in the anterior talofibular
      ligament (ATFL) and calcaneofibular ligament (CFL) and the motion in the
      tibiotalar and subtalar joints during simulated weight-bearing in eight cadaver
      ankle specimens. An MTS test machine was used to apply compressive loads to
      specimens held in a specially designed testing apparatus in which the ankle
      position (dorsiflexion-plantarflexion and supination-pronation) could be varied
      in a controlled manner. The forces in the ATFL and CFL were measured with buckle
      transducers. Tibiotalar motion and total ankle joint motion were measured with an
      instrumented spatial linkage. The specimens were positioned sequentially at 10
      degrees dorsiflexion, neutral, and 10 degrees and 20 degrees plantarflexion, and
      this sequence was repeated at 15 degrees supination, neutral
      pronation/supination, and 15 degrees pronation. Force and motion measurements
      were recorded in each of these positions with and without a 375 N compressive
      load simulating weight-bearing. From 10 degrees dorsiflexion to 20 degrees
      plantarflexion, all motion occurred in the tibiotalar joint. In contrast, the
      ratio of subtalar motion to tibiotalar motion was 3:1 for supination-pronation
      and 4:1 for internal-external rotation. Inverse loading patterns were observed
      for the ATFL and CFL from plantarflexion to dorsiflexion. Compressive loading did
      not affect CFL tension, but it magnified the pattern of increasing ATFL tension
      with plantarflexion. The largest increase in ATFL force was observed in
      supination and plantarflexion with a compressive load (76 +/- 23 N), whereas CFL
      tension mainly increased in supination and dorsiflexion with a compressive load
      (109 +/- 28 N). In conclusion, the results showed that the ATFL acted as a
      primary restraint in inversion, where injuries typically occur (combined
      plantarflexion, supination and internal rotation). Also, the subtalar joint was
      of primary importance for normal supination-pronation and internal-external
      rotation.

PMID- 9604198
TI  - Subtalar arthroscopy--indications and surgical technique.
AB  - Subtalar arthroscopy was performed in 18 patients with different diagnoses. Among
      standard portals the anterolateral ventral (ALV) portal was used for the
      arthroscope and the posterolateral dorsal (PLD) portal for instrumentation. In 4
      patients the subtalar arthroscopy was used only for diagnostic purposes. In 14
      patients arthroscopic surgery was carried out in the same session. The surgical
      procedures were partial synovectomy in 5 patients, resection of a loose body in 3
      patients, a subtalar fusion in 3 patients, debridement of the tarsal sinus in 2
      patients, and a resection of an unfused os trigonum in 1 patient. Subtalar
      arthroscopy is a standardised and reproducible procedure with new diagnostic and
      minimally invasive therapeutic options. We expect this procedure to become
      established in foot surgery in the near future.

PMID- 9604199
TI  - Surgical treatment of pectoralis major rupture in athletes.
AB  - Complete rupture of the pectoralis major muscle, first described by Patissier in
      1822, is a rare sports injury. Less than 100 cases have been reported in the
      literature since 1822. In this study, we describe our surgical technique and
      summarize our results and experience of the surgical treatment of pectoralis
      major rupture. Seven athletes (4 wrestlers, 2 handball players, 1 body-builder)
      were surgically treated in our department from 1981 to 1996. During the follow-up
      examination, five patients had excellent and two had good results, and six
      athletes could return to sports activity at their preoperative level. Among our
      patients we emphasize that of a wrestler, who had suffered an acute rupture, and
      3 months after the surgery he won an Olympic gold medal. According to the
      literature and our experience, we suggest that only surgical repair of the acute
      pectoralis major rupture will result in both complete recovery and restoration of
      the full strength of the muscle, essential for active athletes.

PMID- 9604200
TI  - Anatomy of the proximal musculotendinous junction of the adductor longus muscle.
AB  - Injuries to the adductor longus commonly occur in the proximal part of the muscle
      tendon unit, close to the insertion site on the pubic bone. Ultrasonography,
      magnetic resonance imaging (MRI) and surgery have been helpful in localising the
      lesions, but the exact anatomy of the musculotendinous junction (MTJ) and
      insertion of the muscle remain unclear. We studied the anatomical features of the
      MTJ and measured the dimensions of the tendinous insertion into the pubic bone on
      37 cadavers: 18 men and 19 women. The medial boundaries were the longest part of
      the tendon bilaterally in women, while the lateral aspect of the left muscle was
      greater in men. Tendinous fibres were predominantly found on the anterior
      surface, while the posterior surface consisted mainly of muscle tissue. The MTJ
      was clearly demarcated. There were several types of anomalies present which
      partially explains the difficulty in localising the site of injury and highlights
      the importance of individualized treatment.

PMID- 9604201
TI  - Gilles Bousquet.

PMID- 9604202
TI  - Cadherin-defined segments and parasagittal cell ribbons in the developing chicken
      cerebellum.
AB  - In the developing chicken cerebellar cortex, three cadherins (Cad6B, Cad7, and R
      cadherin) are expressed in distinct parasagittal segments that are separated from
      each other by ribbons of migrating interneurons and granule cells which express R
      cadherin and Cad7, respectively. The segment/ribbon pattern is respected by the
      expression of other types of molecules, such as engrailed-2 and SC1/BEN/DM-GRASP.
      The cadherin-defined segments contain young Purkinje cells which are connected to
      underlying nuclear zones expressing the same cadherin, thereby forming
      parasagittal cortico-nuclear zones of topographically organized connections. In
      addition, R-cadherin-positive mossy fiber terminals display a periodic pattern in
      the internal granular layer. In this layer, Cad7 and R-cadherin are associated
      with synaptic complexes. These results suggest that cadherins play a pivotal role
      in the formation of functional cerebellar architecture by providing a three
      dimensional scaffold of adhesive information.

PMID- 9604203
TI  - Utrophin mRNA expression in muscle is not restricted to the neuromuscular
      junction.
AB  - Utrophin is normally present exclusively in synaptic regions of skeletal muscle
      fibers, although it is expressed extrasynaptically in certain pathological
      situations, where it has been proposed to compensate for the absence of
      dystrophin in Duchenne muscular dystrophy patients and mdx mice. Recently there
      have been conflicting reports regarding the preferential expression of utrophin
      mRNA at the neuromuscular junction. Using in situ hybridization with RNA probes,
      we show a clear accumulation of autoradiographic labeling at more than 90% of
      neuromuscular junctions (identified by histochemical demonstration of
      cholinesterase activity). The intensity of this labeling is proportional to the
      number of junctional myonuclei in the section. Some clusters of labeling were
      found associated with nonmuscle nuclei (e.g., blood vessels, nerves), where
      utrophin is present. In addition, labeling for utrophin mRNA was associated with
      about 25% of extrajunctional myonuclei, where the protein is not present. The
      mean labeling per nucleus at junctional myonuclei was at least 10 times greater
      than at extrajunctional myonuclei. We discuss the possible regulatory mechanisms
      involved in the heterogeneous expression of utrophin mRNA in skeletal muscle.

PMID- 9604204
TI  - Dystonin is essential for maintaining neuronal cytoskeleton organization.
AB  - The mouse neurological mutant dystonia musculorum (dt) suffers from a hereditary
      sensory neuropathy. We have previously described the cloning and characterization
      of the dt gene, which we named dystonin (Dst). We had shown that dystonin is a
      neural isoform of bullous pemphigoid antigen 1 (Bpag1) with an N-terminal actin
      binding domain. It has been shown previously that dystonin is a cytoskeletal
      linker protein, forming a bridge between F-actin and intermediate filaments.
      Here, we have used two different antibody preparations against dystonin and
      detected a high-molecular-weight protein in immunoblot analysis of spinal cord
      extracts. We also show that this high-molecular-weight protein was not detectable
      in the nervous system of all dt alleles tested. Immunohistochemical analysis
      revealed that dystonin was present in different compartments of neurons--cell
      bodies, dendrites, and axons, regions which are rich in the three elements of the
      cytoskeleton (F-actin, neurofilaments, and microtubules). Ultrastructural
      analysis of dt dorsal root axons revealed disorganization of the neurofilament
      network and surprisingly also of the microtubule network. In this context it is
      of interest that we observed altered levels of the microtubule-associated
      proteins MAP2 and tau in spinal cord neurons of different dt alleles. Finally, dt
      dorsal root ganglion neurons formed neurites in culture, but the cytoskeleton was
      disorganized within these neurites. Our results demonstrate that dystonin is
      essential for maintaining neuronal cytoskeleton integrity but is not required for
      establishing neuronal morphology.

PMID- 9604205
TI  - Organizing effects of rapsyn on neuronal nicotinic acetylcholine receptors.
AB  - Targeting receptors to appropriate locations on the cell surface is a critical
      task for neurons. We have examined the possibility that rapsyn controls the
      distribution of nicotinic receptors on neurons as it does nicotinic receptors on
      muscle fibers. Cotransfection of QT6 cells with rapsyn and neuronal nicotinic
      receptor cDNA constructs produced receptor aggregates or clusters that
      codistributed in part with rapsyn protein. Though all nicotinic receptor subtypes
      tested were affected by rapsyn, receptors containing the alpha 7 gene product
      were among the most responsive. In addition, rapsyn caused a portion of the
      nicotinic receptors containing alpha 7 subunits to become resistant to
      solubilization with nonionic detergent and to display a marked increase in
      metabolic stability. The results are consistent with rapsyn linking the receptors
      to cytoskeletal elements and suggest that it may play an organizing role
      determining the fate and location of nicotinic receptors on neurons.

PMID- 9604206
TI  - LAR tyrosine phosphatase receptor: a developmental isoform is present in neurites
      and growth cones and its expression is regional- and cell-specific.
AB  - Transgenic mice and Drosophila mutant studies demonstrate that the leukocyte
      common antigen-related (LAR) protein tyrosine phosphatase (PTPase) receptor is
      required for formation of neural networks. We assessed the hypothesis that
      alternative splicing of the LAR extracellular region contributes to this function
      by establishing temporospatial expression patterns of LAR isoforms containing an
      alternatively spliced extracellular nine amino acid segment (LAR alternatively
      spliced element-c; LASE-c). LASE-c was present in multiple alternatively spliced
      and truncated LAR transcripts. In contrast to LAR isoforms without LASE-c, levels
      of LAR transcripts and protein isoforms containing LASE-c were primarily present
      during development, suggesting a mechanism for developmental regulation of LAR
      function. In situ analysis demonstrated increasingly region- and cell-specific
      expression of LASE-c during maturation. Immunostaining revealed LASE-c-containing
      LAR protein along neurites and in growth cones. The discovery of highly
      regulated, temporospatial extracellular domain alternative splicing of LAR-type
      PTPase receptors points to a novel mechanism by which these receptors might
      influence network formation.

PMID- 9604207
TI  - Alternative splicing of human NrCAM in neural and nonneural tissues.
AB  - Neural cell adhesion molecule NrCAM exists in a variety of isoforms as a result
      of alternative splicing of individual exons during RNA processing. In this report
      we demonstrate that many of the alternative splicing events described for chick
      are conserved in man and describe a novel variant of NrCAM cDNA. Furthermore, we
      show that NrCAM is expressed at significant levels outside the nervous system; in
      particular in pancreas, adrenal glands, and placenta and that expression in both
      brain and other tissues is accompanied by a very variable pattern of exon
      utilization in fetal and adult cells.

PMID- 9604208
TI  - Changes in epidermal growth factor receptor expression and competence to generate
      glia regulate timing and choice of differentiation in the retina.
AB  - Previous studies demonstrated that the level of epidermal growth factor receptors
      (EGF-Rs) expressed by progenitor cells in the newborn (P0) rat retina was
      limiting for the generation of Muller glial cells but not for proliferation. To
      determine whether EGF-R signaling biases cells to generate a specific cell type
      or regulates more general processes during progenitor cell development, we have
      introduced extra copies of the EGF-R into progenitor cells at earlier stages (E15
      and E18), when different cell types are produced. We show that progenitor cells
      in early embryonic retina (E15) normally express lower levels of EGF-Rs than
      progenitor cells in later retina (E18 and P0). Whereas lower levels of
      stimulation of endogenous and virally transduced EGF-Rs enhanced proliferation,
      higher levels reduced proliferation, resulting in premature differentiation. At
      E15, very few EGF-R-Infected progenitor cells differentiated prematurely into
      Muller glial cells, unlike E18 and P0 cells, even when they were exposed to an
      older retinal environment. Higher levels of EGF-R-mediated signaling alone
      therefore do not specify a glial fate, indicating that competence to generate
      glia is temporally regulated by additional mechanisms. The differences in EGF-R
      expression observed among retinal progenitor cells at distinct developmental
      stages may instead help to define signaling thresholds which delay or accelerate
      their differentiation.

PMID- 9604209
TI  - The neuron-glia signal beta neuregulin induces sustained CREB phosphorylation on
      Ser-133 in cultured rat Schwann cells.
AB  - beta neuregulins (also called NDF, GGF, ARIA, and heregulins) are neuron-derived
      molecules that are likely to be responsible for Schwann cell precursor survival,
      proliferation, and maturation in vivo and in vitro. Although the receptors to
      which beta neuregulins bind have been defined, little is known about the
      transcription factors these important ligands activate. Using antibodies,
      quantitative imaging methods and Western blotting, we show that beta neuregulin
      induces a high level of phosphorylation of the transcription factor cyclic AMP
      response element binding protein (CREB) on Ser-133 in cultured rat Schwann cells
      and that the phosphorylation is prolonged over several hours. In contrast,
      neurotrophins, CNTF, FGF-2, EGF, and TGF beta induce little or no phosphorylation
      of CREB despite the fact that receptors for these factors are present on Schwann
      cells. As expected CREB phosphorylation was detected following cAMP elevation,
      and it was also induced by elevation of cytoplasmic Ca2+, endothelin 1, and PDGF
      BB. The signal was lower than that seen in response to beta neuregulin, and
      transient, unlike the sustained CREB activation induced by beta neuregulin. Our
      results suggest that the sustained phosphorylation of CREB on Ser-133 may
      contribute to the broad spectrum of effects that beta neuregulins have on cells
      of the Schwann cell lineage and that the CREB pathway may be important for
      transduction of neuregulin signals in Schwann cells.

PMID- 9604210
TI  - Role of G-proteins and second messenger systems in the plasticity of a defensive
      reflex in the common snail.
AB  - Enzymatic methods were used to demonstrate an increase in the activity of G
      proteins and protein kinase A in the brain of the common snail at early stages of
      learning. There were no differences in the activity of G-proteins in the brain
      between young (unable to learn) and adult snails. Snail brain protein kinase C
      activity was unchanged compared to controls 20-40 minutes after the end of the
      training procedure. It is concluded that cAMP-dependent phosphorylation and cAMP
      dependent activation of early gene expression have active roles in learning in
      the snail. The question of the role of additional intracellular regulatory
      systems in learning in the snail is discussed.

PMID- 9604211
TI  - Responses of cortical neurons to microiontophoretic application of acetylcholine
      to their dendrites.
AB  - Spike responses of neurons to the microiontophoretic application of acetylcholine
      to the soma and the dendrites were studied. The somatic and dendritic membranes
      had virtually equal sensitivity to acetylcholine. Only activatory responses were
      seen, which were most typical of spontaneously active neurons. Muscarinic
      activation induced spike responses with equal latent periods and equal
      intensities on application of acetylcholine to dendrites and the soma. It is
      suggested that intracellular chemical signaling is involved in the propagation of
      cholinergic excitation via dendrites.

PMID- 9604212
TI  - Nootropic agent vinpocetine blocks delayed rectified potassium currents more
      strongly than high-threshold calcium currents.
AB  - A two-microelectrode potential clamping method was used on isolated common snail
      neurons to measure high-threshold Ca2+ and delayed rectified K+ currents.
      Addition of the nootropic agent vinpocetine (VPC) to the bathing solution rapidly
      and reversibly inhibited both types of current. The effects of VPC were dose
      dependent and were independent of the test stimulus voltage. Maximum blockade of
      the Ca2+ current averaged 27% at a VPC concentration of 600 microM. Maximum
      blockade of the K+ current averaged 76% at a VPC concentration of 30 microM. It
      is concluded that K+ channels are more likely targets of VPC than Ca2+ channels.

PMID- 9604213
TI  - Studies of long-term potentiation and depression of inhibitory transmission by
      mathematical modeling of post-synaptic processes.
AB  - A mathematical model of posttetanic processes launched by rhythmic stimulation of
      the excitatory and inhibitory inputs to the dendritic spine of a pyramidal neuron
      in hippocampal field CA3 was used to study conditions for modifying the
      efficiency of the inhibitory input. The level of dephosphorylation of GABAa and
      GABAb receptors, which determines the GABA sensitivity of these receptors, was
      shown to depend on the Ca(2+)-dependent ratio of active protein kinases and
      protein phosphatases; the level of dephosphorylation decreased monotonically as
      the intracellular Ca2+ increased. Posttetanic increases and decreases in the Ca2+
      concentration, as compared with the level achieved during the previous
      stimulation, led to increases or decreases respectively in the number of
      dephosphorylated GABA receptors and to induction of long-term potentiation and
      depression, respectively, in the efficiency of inhibitory transmission. The
      extent of the modification effect depended on the ratio of the quantities of
      inhibitory and excitatory mediators in the synaptic cleft. At very low or very
      high GABA concentrations, modification of inhibitory transmission was
      insignificant.

PMID- 9604214
TI  - Comparison of the effects of dopamine agonists on self-stimulation of the
      hypothalamus with lesioning of mesolimbic brain structures in rats reared in
      conditions of social isolation.
AB  - Initial and phenamine-stimulated frequencies of self-stimulation of the lateral
      hypothalamus were not significantly different in rats reared in communities and
      in conditions of social isolation. Unilateral lesioning of the ventral tegmental
      area and the medial prefrontal cortex in early ontogenesis increased phenamine
      sensitivity only in isolated rats. The dopamine receptor agonist apomorphine, at
      a dose of 0.05 mg/kg, which affects presynaptic receptors, inhibited the self
      stimulation response in intact group-reared animals and in rats reared in
      isolation, by 21-23%. Stimulation of the ventral tegmental area did not change,
      while stimulation of the medial prefrontal cortex doubled the sensitivity of rats
      to apomorphine in animals reared in isolation (at doses of 0.05 and 0.5 mg/kg).
      Conditions of partial sensory and complete species isolation resulted in the
      development of a state of presynaptic receptor hypersensitivity of dopamine
      receptors in mesocorticolimbic brain systems in rats.

PMID- 9604216
TI  - Neuronal network simulating the simultaneous contrast of equiluminant colors.
AB  - A vector model for the simultaneous contrast of equiluminant colors is proposed.
      The main characteristics of simultaneous color contrast are associated with the
      interaction of the test and induction fields. The mechanisms of color contrast
      depend on the activity of neurons which subtract excitation arising in analogous
      neurons of the test and induction fields. Signals from the "subtractor" neurons
      pass via local inputs to "adder" neurons. Selective color detectors are excited
      by contributions from the adder neurons. When the induction and test fields are
      of identical color and their excitation vectors coincide, the color of the test
      field depends on neurons excited only in the test field, and the induction field
      has no effect on the color of the test field. When the test and induction fields
      are of different color tone or saturation, the color of the induction field
      affects the color of the test field such that the excitation vector of the test
      field diverges from the excitation vector of the induction field. This model can
      be used for analysis of neurophysiological and psychophysiological studies of
      color contrast.

PMID- 9604215
TI  - Duration of the persistence of movement activity in rats induced by single
      injections of haloperidol.

PMID- 9604217
TI  - Mechanism of organization of different types of directed movements.
AB  - This article considers the mechanism for construction of movements in biological
      systems as a means of reducing excess degrees of freedom of a motor organ. It is
      suggested that each type of excess of degrees of freedom is reduced by one of the
      hierarchically coordinated systems of motor control. Detailed consideration is
      given to mechanisms for reducing the dynamic excess of a motor organ, the
      kinematic excess associated with polyarticular motor organs, and the kinematic
      excess of the desired trajectory. A functional scheme is developed for a motor
      control system which reduces these excess degrees of freedom, and the control
      processes for various types of movement were studied by computer modeling.

PMID- 9604218
TI  - Effects of a number of short peptides isolated from the brain of the hibernating
      ground squirrel on the EEG and behavior in rats.
AB  - Intracerebroventricular administration of the peptides kyotorphin (Tyr-Arg),
      neokyotorphin (Thr-Ser-Lys-Tyr-Arg), and Asp-Tyr at doses of 4 and 8 micrograms
      altered the behavior of rats in a manner similar to that seen after similar
      administration of brain fractions from hibernating ground squirrels (Citellus
      undulatus), which contained these peptides; there were increases in orientational
      reactions, increases in the frequency of stereotypical scratching movements,
      grooming, yawning, hiccuping, and sneezing. Animals became drowsy after 15-20
      min. Peptides and brain fractions also had similar effects on the EEG of rats.
      Brain fractions reduced theta and alpha rhythms and enhanced delta and beta
      frequencies. Increases in delta waves were seen with all peptides (a 4-microgram
      dose of kyotorphin produced alternating increases and reductions in the delta
      rhythm). Inhibition of theta and alpha rhythms after administration of Asp-Tyr
      and kyotorphin was more transient than after brain fractions. Increases in beta
      frequencies were seen only after administration of 8 micrograms of Asp-Tyr, the
      smaller dose not producing this effect.

PMID- 9604219
TI  - Effect of stimulation of the lateral hypothalamus on the correlation of neuron
      spike activity in the rabbit neocortex.
AB  - Cross-correlation and autocorrelation histograms were constructed with the aim of
      studying correlated spike activity of neurons in the visual and sensorimotor
      regions of both hemispheres of the rabbit brain before and after stimulation of
      the right and left lateral hypothalamic regions, which generates food-motivated
      responses. Stimulation of the left hypothalamus produced larger rearrangements in
      correlated neuron firing than stimulation of the right hypothalamus. Stimulation
      of the left hypothalamus, unlike that of the right hypothalamus, was followed by
      significant increases in the numbers of pairs of left hemisphere neocortical
      neurons with linked activity, and also induced the sequential firing of neurons
      in a particular defined order: sensorimotor cortex cells fired first, followed by
      visual cortex neurons after delays of up to 120 msec. It is concluded that
      cortical interhemisphere asymmetry in conditions of hunger is associated with
      nonuniform functioning of the right and left lateral hypothalamic regions.

PMID- 9604220
TI  - Contrasting of synaptic signals by simultaneous modification of excitatory and
      inhibitory inputs.
AB  - Conditions facilitating long-term contrasting of interneuronal connections were
      studied using a mathematical model of posttetanic Ca(2+)-dependent postsynaptic
      processes in pyramidal neurons of hippocampal field CA3. These studies
      demonstrated that modified inhibition selectively facilitates. long-term
      potentiation of the efficiency of one of the interneuronal connections when the
      presynaptic neuron discharges at a given frequency for a short time, while
      connections formed from the same postsynaptic cell with other presynaptic neurons
      undergo long-term depression. The mechanism underlying this contrasting may
      involve long-term depression of the efficiency of disynaptic inhibitory
      transmission to the rhythmically stimulated input, even when the efficiency of
      monosynaptic excitatory transmission at the same input is low and undergoes
      minimal potentiation. When the "common" inhibitory neuron is simultaneously
      activated by various presynaptic cells. heterosynaptic potentiation of inhibitory
      transmission can simultaneously develop at the other inputs of the postsynaptic
      cell, without change in the efficiency of excitatory transmission, which leads to
      long-term depression of the efficiency of the connections between other
      excitatory neurons and the postsynaptic cell.

PMID- 9604221
TI  - Long-term posttetanic changes in the background activity of neurons in both
      hemispheres.

PMID- 9604223
TI  - Assessment of contrast sensitivity in kittens after the critical developmental
      period.
AB  - Spatial contrast sensitivity was measured in kittens aged 6, 9, and 12 months and
      in adult cats. Cats had to open one of two small windows, which had a photograph
      of a grid, in order to obtain food reinforcement. The nonreinforced stimulus was
      a photograph of a uniform field of the same mean luminance. Visual acuity was
      constant in kittens aged 6 to 12 months. However, six-month-old kittens had low
      contrast sensitivity at low spatial frequencies (< 0.6 cycles/degree). At the age
      of nine months, contrast sensitivity over this range increased, though the level
      seen in adult cats was reached only at the age of 12 months. It is suggested that
      the increase in contrast sensitivity occurring after the critical developmental
      period in kittens reflects maturation of higher-order cortical fields involved in
      the process of recognition.

PMID- 9604222
TI  - Functional importance of alpha-activity in the visual cortex during recognition
      of images and movement.
AB  - Twenty-seven studies were carried out on the recognition of the shapes of
      geometrical figures of different sizes by healthy adults, on the recognition of
      the direction of movement of a light spot within the field of vision, and of
      visual illusions produced by rhythmic visual stimulation. Tachystoscopic
      presentation of figures and the onset of movement were synchronized with
      different phases of the EEG alpha-rhythm in the occipital region. In controls,
      stimuli were presented without a shift in the alpha-rhythm. Recognition improved
      significantly when small figures were presented at relatively late phases of the
      alpha-wave and when large figures (up to 9 degrees) were presented at relatively
      early phases. Recognition of the side and direction of apparent movement (in the
      left or right halves of the visual field and centrifugal or centripetal) depended
      on the phase of the alpha-wave only for nonuniform (accelerating or decelerating,
      depending on direction) movement, allowing for the cortical magnification factor.
      Centrifugal movements in experiments were recognized better than in controls,
      while centripetal movements were recognized worse, and elicited a relatively long
      latency movement response. Diffuse rhythmic light stimulation at the alpha-rhythm
      frequency produced the illusory percept of a ring or circle in 11 of 12 subjects.
      The optimal stimulation frequency for this was tightly connected with the
      dominant alpha-rhythm frequency, with a correlation coefficient of 0.86. The link
      between these effects and the propagation of the wave process through the visual
      cortex, as reflected by the EEG alpha-rhythm, is discussed. The data support the
      hypothesis of Pitts and McCulloch [29], which proposes scanning of the visual
      cortex by a wave process operating at the frequency of the alpha-rhythm, which
      reads information from the visual cortex.

PMID- 9604224
TI  - Effect of electrical stimulation of the mamillary nuclei of the hypothalamus on
      skin vessel permeability in intact and capsaicin-treated rats.
AB  - Stimulation of the mamillary nuclei of the rat hypothalamus induced increases in
      the permeability of forelimb skin microvessels. This effect was not seen in rats
      stimulated after administration of capsaicin at a dose (150 mg/kg) sufficient to
      deplete vasoactive neuropeptides from the peripheral nerve terminals of capsaicin
      sensitive neurons. These data indicate a role for the mamillary nuclei in central
      mechanisms modulating the effector functions of primary capsaicin-sensitive
      neurons.

PMID- 9604225
TI  - Agonistic behavior during stress prevents the development of learned helplessness
      in rats.
AB  - Male Wistar rats were subjected to unavoidable electrical pain stimulation either
      in individual cages or in pairs. During the procedure, rats stressed in pairs
      fought. After 48 h, rats were tested in a shuttle box for the ability to develop
      active avoidance responses. The proportion of escape and avoidance responses was
      significantly lower in rats stressed individually as compared with intact animals
      and animals stressed in pairs. Plasma corticosterone was assayed one day later,
      at rest and after dexamethasone administration. There were no significant
      differences in resting corticosterone level between groups of animals.
      Administration of dexamethasone significantly reduced the plasma corticosterone
      level in intact rats and in animals stressed in pairs, but not in rats stressed
      individually. Thus, agonistic behavior during unavoidable stress prevents the
      development of pathological changes in adaptive behavior and the endocrine
      system.

PMID- 9604226
TI  - Asymmetry of the internal connections of the striate cortex of the cat in the
      projection zone of the center of the field of vision.
AB  - Studies were carried out on the organization of the internal connections of the
      striate cortex in cats in the projection zone of the center (0-5 degrees) of the
      field of vision by microintophoretic application of horseradish peroxidase to
      electrophysiologically identified orientational columns. The area containing
      neurons showing retrograde labeling in most cases extended in the mediolateral
      direction. Labeled cells were located in the upper (II, III) and lower (V, VI)
      layers of the cortex, and the shapes and orientations of the areas containing
      labeled neurons in these layers coincided. Spatial asymmetry was detected in the
      distribution of labeled neurons relative to the orientational column studied.
      Labeled cells were located predominantly medial to the columns, regardless of the
      distance from the projection of the area centralis. Considering the visuotopical
      map of field 17, the asymmetry detected here provides evidence that neurons in
      orientational columns have more extensive connections with neurons of the
      peripheral part of the cortex. An asymmetrical distribution of "silent" 2 zones
      around the receptive fields of neurons in orientational columns is suggested, and
      that these appear to receive influences from the periphery of the visual field.

PMID- 9604228
TI  - [Individual outcome monitoring of TSH receptor antibody level for predicting the
      prognosis of Graves' disease].
AB  - AIM: This retrospective study is intended to provide further information on the
      controversially discussed ability of a Thyrotropin Receptor Antibody (TRAb)
      monitoring for predicting the outcome of Graves' disease. METHOD: The study is
      based on 1480 blood samples of 346 patients (292 female, 54 male; age among 9 and
      91 years) suffering from Graves' disease. A comparison between the TRAb levels
      and the serum free thyroid hormones as well as the basal thyrotropin was
      performed in the entire collective, in the group of non-treated patients and in
      182 individual courses. RESULTS: Even in comparable states of function, the
      individual TRAb levels were quite divergent. In the group with persistent
      dysfunction, they initially varied between 6 and 482 U/l (normal range < 15 U/l).
      A global evaluation of the particular groups hence did not show any correlation
      between the functional disorder and the respective TRAb levels. However, when
      considering the individual courses, a distinct dependence upon the development of
      the TRAb could be observed. As the limit for separating the group suffering from
      persistent malfunction or recurrence and the collective in remission, a decline
      of the individual TRAb level below 50% of the initial value has proven to be most
      suitable. This was observed in 94% of all remissions. In 90% of all relapsed
      patients, we either found persistent high TRAb levels (i.e. a maximum decrease
      down to 50% of the initial value) or another increase of the TRAb levels. The
      positive and negative predictive values of the method are 97% and 58%,
      respectively. CONCLUSION: The outcome of Graves' disease depends on the
      individual changes of the TRAb levels rather than on their absolute values. In
      case of persistent TRAb, you have to expect a continuing dysfunction or a
      recurrence.

PMID- 9604227
TI  - [Determination of factors affecting the therapeutic outcome of radioiodine
      therapy in patients with Graves' disease].
AB  - AIM: Of this study was to determine whether success of radioiodine therapy (RIT)
      in Graves' disease depends on thyroid volume, function, thyroideal receptor
      antibodies (TRAK), thyreostasis, therapeutic dosage, 131I uptake, or effective
      half-life. METHOD: 78 patients received an average of 626 +/- 251 MBq of iodine
      131 orally for thyroid ablation. 60 were assessed for successful therapy 3 months
      after RIT. RESULTS: In patients showing hyperthyreosis or a TRAK value > 11 U/l
      at the beginning of RIT, a significantly lower therapeutic dosage and effective
      iodine half-life were found than in non-hyperthyreotic patients or patients with
      TRAK < or = 11 U/l. Patients with a thyroid volume < or = 25 ml showed a
      significantly lower 131I uptake, but a significantly higher relative uptake (131I
      uptake/ volume) than patients with a thyroid volume > 25 ml. All failures were
      treated thyreostatically during RIT and showed a significantly lower therapeutic
      iodine dosage and relative uptake, as well as a significantly higher thyroid
      volume than patients with a successful therapy. RIT caused a thyroid volume
      reduction of 44%, with therapy failures showing a significantly lower volume
      reduction. Patients who received a therapeutic dosage of < or = 250 Gy showed
      significantly worse results than did those who had received > 250 Gy. Only one
      case of therapy failure received a dosage > 250 Gy, while 50% of failures
      received dosages > 200 Gy but < 250 Gy. Multivariate analyses (MANOVA, factor
      analyses) showed thyreostasis as the decisive negative factor for a successful
      course of therapy. CONCLUSIONS: Since most treatment failures occurred in
      patients under thyreostatic medication we recommend raising the target dosage to
      250 Gy for these cases.

PMID- 9604229
TI  - [Euthyroid goiter with and without functional autonomy in the euthyroid phase: a
      comparison].
AB  - AIM: Analysis of functional autonomy in euthyroid goitre. METHODS: In an area of
      moderate iodine deficiency 163 goitrous patients without and 179 with functional
      autonomy all clinically euthyroid were compared by sex, age, signs and symptoms,
      sonographic results, qualitative and quantitative scintigraphy without and with
      suppression, TRH test, hormone concentrations and iodine excretion in the urine.
      RESULTS: Age, signs and symptoms, thyroid volume and structure did not contribute
      sufficiently to diagnosis. To detect functional autonomy quantitative
      scintigraphy under suppression was superior to the TRH test. Increased hormone
      concentrations were observed in 15% of patients with functional autonomy. A
      global 99mTc thyroid uptake of > or = 3% under suppression indicates a higher
      risk of spontaneous hyperthyroidism. It was present in 20% of patients with
      functional autonomy. CONCLUSION: To diagnose and treat adaequately functional
      autonomy in euthyroid goitre quantitative scintigraphy, determination of TSH and
      hormone concentrations are inevitable.

PMID- 9604230
TI  - [Combination therapy of endemic goiter with two different thyroxine/iodine
      combinations].
AB  - AIM: Of this study was to investigate the extent of thyrotropin (TSH) suppression
      and volume reduction in combination therapy of endemic goitre. We compared an
      individually adapted dose of thyroxine with a fixed dose. METHODS: 105 patients
      of a multicenter study (randomised, single blinded, controlled) received daily a
      weight-adjusted LT4-dose in combination with 150 micrograms iodide (group A) or a
      fixed combination of 100 micrograms LT4 plus 100 micrograms iodide (group B),
      respectively. At the beginning and after 12 weeks TSH-levels and goitre volume
      were examined. RESULTS: Although the amount of thyrotropin suppression showed no
      differences in both groups, there were more patients in the weight-adjusted
      treatment group with completely suppressed thyrotropin serum concentrations (p <
      0.05). Both groups showed a reduction of goitre volume of 24% CONCLUSION: A
      weight-adjusted LT4-dose of 1.4 micrograms/kg body weight often leads to
      subclinical hyperthyroidism. To obtain low TSH-levels without complete
      suppression LT4-doses of 1.0 microgram/kg body weight plus 150 micrograms iodide
      are probably sufficient.

PMID- 9604231
TI  - Influence of radioiodine therapy on urinary iodine excretion.
AB  - AIM: In 214 patients with benign thyroid diseases the time-course of urinary
      iodine excretion (UIE) was investigated in order to identify changes after
      radioiodine therapy (RITh). METHOD: UIE was measured photometrically (cerium
      arsenite method) and related to urinary creatinine on the first and last day of
      the radioiodine test and then three days, seven days, four weeks, and six months
      after 131I administration. RESULTS: As compared with the level found immediately
      before radioiodine therapy, median UIE had almost doubled four weeks after
      therapy and was still significantly elevated six months after therapy. This
      increase correlated significantly with the target volume as measured by
      scintigraphy and sonography. CONCLUSIONS: The persistent elevation of UIE for
      months after RITh is a measure of treatment-induced damage to thyrocytes.
      Therefore, in view of the unfavourable kinetics of iodine that follow it, RITh
      should if possible be given via a single-dose regime.

PMID- 9604232
TI  - [Exposure of relatives of patients after stationary radioiodine therapy by
      inhalation of 131I in their homes].
AB  - AIM: From a model of iodine metabolism exhalation coefficients shall become
      derived to calculate 131I exhalation by patients after a radioiodine treatment.
      The validity of these exhalation coefficients shall be reviewed by whole body
      activity measurements of relatives of patients, who inhaled the radioiodine
      exhaled by the patients in their homes. The exposure of relatives to patients of
      a nuclear medical ward after release by exhalation of iodine-131 is investigated.
      METHODS: Iodine 131I-activity of 17 relatives to patients who had to undergo a
      radioiodine therapy became measured in a whole body counter only a few days after
      release of the patient from the nuclear medical ward. The results of the
      measurements have been compared with the results of calculations according to the
      model of iodine metabolism. RESULTS: The calculated values of incorporated
      radioiodine in the relatives of the patient at time of measurement (Amodel)
      correlate with the measured whole body activity (AGK) according to the
      regression: Amodel = AGK -47.3 (r2 = 0.959). This relation holds if 2.1
      micrograms of iodine become exhaled per day of the 60 micrograms of iodine which
      are the daily intake of iodine by food. The exposure of all relatives did never
      exceed 100 microSveff. Using the same model parameters the effective dose
      equivalent of the relatives to our patients rises up to 6.5 mSv under ambulant
      radio therapy condition. CONCLUSION: The daily exhalation of 131I is able to be
      calculated by a mathematical model of iodine metabolism. After staying of
      patients at least 3 days in a nuclearmedical ward the exposure of relatives of
      patients in their home does not exceed the value of 100 microSveff by inhalation
      of iodine-131. This are 10% of the limit of 1 mSveff according to the
      Recommendations of the Commission on Radiological Protection (ICRP 60).
      Radioiodine therapy outside of a hospital and "iodine therapy tourisme" of German
      patients to other countries cannot be accepted.

PMID- 9604234
TI  - Taking the "idio" out of "idiosyncratic": predicting torsades de pointes.

PMID- 9604233
TI  - [Measurement of incorporation in family members of radioiodine therapy patients
      after therapy of benign thyroid diseases].
AB  - AIM: Patients exhale I-131 after radioiodine therapy. In this study we quantify
      the amount of radioactivity and resulting thyroid doses found in people living in
      close contact to patients treated with I-131 after their release from a therapy
      ward. METHODS: For 31 relatives of 25 patients treated with I-131 the
      incorporation was monitored using the thyroid probe of a whole body counter.
      These values are used for a determination of thyroid doses. RESULTS: 11 of the 31
      monitored persons had a thyroid activity of less than the minimal detectable
      activity of 13 Bq. The mean value of the remaining 20 people was 104 Bq in the
      thyroid resulting in a mean thyroid dose of 0.2 mSv (Maximum: 2 mSv). CONCLUSION:
      The intake of I-131 for persons in close contact to patients after dismissal from
      a therapy ward is low. In no case an effective dose exceeding 1 mSv was observed.

PMID- 9604235
TI  - An optimized AV delay algorithm for patients with intermittent atrioventricular
      conduction.
AB  - Detection and promotion of an intermittent atrioventricular (AV) conduction is
      the objective of an AV delay hysteresis algorithm in dual chamber pacemaker (DDD)
      pacing. The AV delay following an atrial event is automatically extended by a
      programmable interval (AV hysteresis interval) if the previous cycle showed
      spontaneous AV conduction, i.e., a ventricular event was detected within the
      previous AV delay. An automatic search mode scans for spontaneous ventricular
      events during the hysteresis interval: a single AV delay extension (equal to the
      programmed AV delay hysteresis) will occur after a successive, programmable
      number of AV cycles with ventricular pacing. If a spontaneous AV conduction is
      present, the AV delay will remain extended by the hysteresis interval. Our first
      results in 17 patients with intermittent AV block disclosed a satisfactorily
      working algorithm with effective reduction of ventricular stimuli. In relation to
      the underlying conduction disturbance and pacemaker settings, the majority of our
      patients showed a reduction of ventricular pacing events up to 90% without any
      adverse hemodynamic or electrophysiological changes. Based on clinical (promotion
      of a physiological activation and contraction sequence) and technical (reduction
      of power consumption) advantages, the AV hysteresis principle could be of
      incremental value for future dual chamber pacing in patients with intermittent
      complete heart block.

PMID- 9604236
TI  - Electrocardiographic and clinical predictors of torsades de pointes induced by
      almokalant infusion in patients with chronic atrial fibrillation or flutter: a
      prospective study.
AB  - The aim of this study was to identify predictors of torsades de pointes (TdP) in
      patients with atrial fibrillation (AF) or flutter exposed to the Class III
      antiarrhythmic drug almokalant. TdP can be caused by drugs that prolong
      myocardial repolarization. One hundred patients received almokalant infusion
      during AF (infusion 1) and 62 of the patients during sinus rhythm (SR) on the
      following day (infusion 2). Thirty-two patients converted to SR. Six patients
      developed TdP. During AF, T wave alternans was more common prior to infusion
      (baseline) in patients developing TdP (50% vs 4%, P < 0.01). After 30 minutes of
      infusion 1, the TdP patients exhibited a longer QT interval (493 +/- 114 vs 443
      +/- 54 ms [mean +/- SD], P < 0.01), a larger precordial QT dispersion (50 +/- 74
      vs 27 +/- 26 ms, P < 0.05), and a lower T wave amplitude (0.12 +/- 0.21 vs 0.24
      +/- 0.16 mV, P < 0.01). After 30 minutes of infusion 2, they exhibited a longer
      QT interval (672 +/- 26 vs 489 +/- 74 ms, P < 0.001), a larger QT dispersion in
      precordial (82 +/- 7 vs 54 +/- 52 ms, P < 0.01) and extremity leads (163 +/- 0 vs
      40 +/- 34 ms, P < 0.001), and T wave alternans was more common (100% vs 0%, P <
      0.001). Risk factors for development of TdP were at baseline: female gender,
      ventricular extrasystoles, and treatment with diuretics; and, after 30 minutes of
      infusion: sequential bilateral bundle branch block, ventricular extrasystoles in
      bigeminy, and a biphasic T wave. Patients developing TdP exhibited early during
      almokalant infusion a pronounced QT prolongation, increased QT dispersion, and
      marked morphological T wave changes.

PMID- 9604237
TI  - An algorithm for automatic measurement of stimulation thresholds: clinical
      performance and preliminary results.
AB  - We have developed an algorithmic method for automatic determination of
      stimulation thresholds in both cardiac chambers in patients with intact
      atrioventricular (AV) conduction. The algorithm utilizes ventricular sensing, may
      be used with any type of pacing leads, and may be downloaded via telemetry links
      into already implanted dual-chamber Thera pacemakers. Thresholds are determined
      with 0.5 V amplitude and 0.06 ms pulse-width resolution in unipolar, bipolar, or
      both lead configurations, with a programmable sampling interval from 2 minutes to
      48 hours. Measured values are stored in the pacemaker memory for later retrieval
      and do not influence permanent output settings. The algorithm was intended to
      gather information on continuous behavior of stimulation thresholds, which is
      important in the formation of strategies for programming pacemaker outputs.
      Clinical performance of the algorithm was evaluated in eight patients who
      received bipolar tined steroid-eluting leads and were observed for a mean of 5.1
      months. Patient safety was not compromised by the algorithm, except for the
      possibility of pacing during the physiologic refractory period. Methods for
      discrimination of incorrect data points were developed and incorrect values were
      discarded. Fine resolution threshold measurements collected during this study
      indicated that: (1) there were great differences in magnitude of threshold
      peaking in different patients; (2) the initial intensive threshold peaking was
      usually followed by another less intensive but longer-lasting wave of threshold
      peaking; (3) the pattern of tissue reaction in the atrium appeared different from
      that in the ventricle; and (4) threshold peaking in the bipolar lead
      configuration was greater than in the unipolar configuration. The algorithm
      proved to be useful in studying ambulatory thresholds.

PMID- 9604238
TI  - Reproducibility of tilt table testing in patients with vasovagal syncope and its
      relation to variations in autonomic nervous system activity.
AB  - To assess the variability of head-up tilt table testing, 35 patients with
      vasovagal syncope, shown by a positive tilt table test, underwent a second test 1
      week later. Also, on the day before each test, spectral and time-domain indexes
      of heart rate variability were derived from Holter recordings to examine the
      stability of autonomous nervous system activity in these patients. Fifteen
      healthy volunteers served as a control group and also underwent two tilt table
      tests with prior Holter monitoring. Twenty-one (60%) of the 35 patients had a
      second positive test. None of the patients in the control group experienced
      syncope during either of the tests. The heart rate variability measures in the
      control group varied slightly from 1 day to the other, in contrast to the
      syncopal patients, where only low frequency spectral power and the mean of all 5
      minute standard deviations of RR intervals showed comparable behavior. The
      indexes which reflect parasympathetic activity exhibited significant fluctuations
      in the syncopal patients. These fluctuations were due entirely to the patients
      who did not reproduce the outcome of the tilt table test, where high
      parasympathetic tone was associated with the positive test and normal
      parasympathetic tone with the negative test. In contrast, the patients with two
      positive tests had high parasympathetic tone during both test periods, with low
      individual variability. In conclusion, patients with vasovagal syncope show
      variations in vagal autonomic tone and appear to be more prone to syncope when
      their parasympathetic tone is elevated.

PMID- 9604239
TI  - Systolic and diastolic function with alternate and combined site pacing in the
      right ventricle.
AB  - We hypothesized that pacing at two ventricular sites simultaneously would
      activate the myocardium more rapidly and improve ventricular function. We studied
      the effect of pacing at the right ventricular outflow tract (RVOT) and the RV
      apex (RVA) on systolic and diastolic function. In 14 patients with a reduced
      systolic ejection fraction < 40% (mean EF 32% +/- 4%) we measured RV pressures,
      left ventricular pressures, EF, cardiac output, peak dP/dt, peak negative dP/dt,
      and the time constant of relaxation, Tau, during intrinsic rhythm, atrial pacing
      and DVI pacing at the RVA, the RVOT, and both RV sites combined in random order.
      Repeated measures analysis of variance showed no significant differences in any
      of these parameters. The highest absolute values of dP/dt were observed during
      sinus rhythm and the lowest with RVA pacing. This parameter tended to improve
      progressively with pacing in the RVOT and at both sites. Peak negative dP/dt
      showed a similar nonsignificant trend. CONCLUSION: These data suggest that in
      patients with poor LV function, there may be subtle improvements in diastolic and
      systolic function with pacing in the RVOT and at combined sites in the RV
      compared to traditional RVA pacing.

PMID- 9604240
TI  - Physiology of the escape rhythm after radiofrequency atrioventricular junctional
      ablation.
AB  - The physiology of the escape rhythm (ER) and its response to pharmacological
      modulation under varying autonomic conditions were studied 48 patients undergoing
      radiofrequency ablation of the atrioventricular junction (AVJ) for refractory
      atrial fibrillation. The QRS morphology and cycle length (CL) of the baseline ER
      were measured 15 minutes postablation. The CL of the ER was measured in response
      to doses of isoproterenol, atropine, adenosine, lidocaine, and verapamil. The ER
      QRS was narrow (QRS < 120 ms) in 20 patients and wide (QRS > 120 ms) in 28
      patients. Of the 28 patients with wide QRS ER, 11 patients had a new bundle
      branch block (8 patients new right bundle branch block [RBBB] and 2 patients new
      left bundle branch block [LBBB]). The ERCL was similar in both narrow and wide
      ERs (1,593 +/- 376 ms and 1,516 +/- 296 ms, P = 0.44). In 23 patients receiving
      isoproterenol infusion, the ER CL decreased with increasing doses from 1 mcg/min
      to 2 mcg/min (1,378 +/- 200 to 1,240 +/- 229 ms, P < 0.001), but did not decrease
      further at 3 mcg/min (1,201 +/- 192 ms, P = 0.48 vs 2 mg/min). Seven patients
      received 0.02 mg/kg of atropine, and ER decreased significantly (1,572 +/- 408 ms
      to 1,319 +/- 333 ms, P = 0.028). In 30 patients who received intravenous boluses
      of adenosine (6-18 mg), the ER did not change significantly. In 28 patients who
      received 150 mg of lidocaine, the ER increased from 1,462 +/- 286 ms to 1,715 +/-
      467 ms (P < 0.001), and one patient developed transient asystole. Nineteen
      patients received 7.5 mg of verapamil, and the ER did not change (1,488 +/- 313
      ms to 1,513 +/- 666 ms, P = 0.80). There was no significant difference in
      response to isoproterenol, adenosine, lidocaine, or verapamil between the
      patients with wide and narrow QRS ERs. We conclude that patients may have stable
      ERs immediately following AVJ ablation even when a wide complex ER results. The
      ER is responsive to sympathetic stimulation and vagal blockade. The ER is
      prolonged after lidocaine but not after verapamil, suggesting response to sodium
      but not to calcium channel blockade. These data are consistent with an ER
      originating in the distal compact AV node or proximal His bundle.

PMID- 9604241
TI  - The effect of inducing ventricular fibrillation with 50-Hz pacing versus T wave
      stimulation on the ability to defibrillate.
AB  - When testing an ICD, there are at least two techniques for inducing ventricular
      fibrillation: (1) high frequency (approximately equal to 50 Hz) pacing; and (2) a
      single T wave stimulus. It is generally assumed that these two methods yield
      similar results. This study directly tested this assumption. In six dogs, one
      defibrillation electrode was placed in the right ventricular (RV) apex and the
      second was placed cutaneously on the left thorax. All defibrillation and T wave
      stimuli were biphasic between these two electrodes. Pacing was monophasic from
      the tip of the RV catheter to the cutaneous patch. The voltage which
      defibrillates 50% of the time (DF50) was measured using a 10-step Bayesian up
      down method. Observations for two DF50 measurements were randomly interleaved.
      For one DF50 measurement, fibrillation was induced with 99 pacing stimuli at a 20
      ms pacing interval (50-Hz pacing). For the second DF50 measurement, fibrillation
      was induced with a single defibrillation shock of approximately 1/2 J delivered
      at a time corresponding to the peak of the T wave in the lead II electrogram (T
      wave stimuli). The average DF50 when measured after fibrillation induced with 50
      Hz pacing was 379 +/- 54.6 V, as compared to 382 +/- 50.3 V when fibrillation was
      induced with T wave stimuli. The difference of 3 V was not statistically
      significant. If these results are confirmed in humans, it is reasonable to assume
      that the efficacy of a defibrillation shock is the same whether T wave stimuli or
      50-Hz pacing are used to induce fibrillation.

PMID- 9604242
TI  - Long-term performance of bipolar epicardial atrial pacing using an active
      fixation bipolar endocardial lead.
AB  - Bipolar epicardial leads are not yet widely available for atrial use. Since
      September 1986, we have used a bipolar active fixation endocardial lead (Cardiac
      Pacemakers model number's 4266, 4268, and 4269) as a bipolar epicardial atrial
      lead by attaching the corkscrew tip to the atrial surface and imbricating atrial
      tissue around the more proximal electrode. A total of 77 bipolar epicardial
      atrial leads have been implanted using this approach in 72 patients with
      congenital heart disease (ages 3 months to 38.7 years; mean 8.9 +/- 8.8 years).
      Indications for atrial pacing included AV block (n = 46), sinus node dysfunction
      (n = 17), and antitachycardial pacing (n = 9). Indications for epicardial pacing
      included the presence of an intracardiac right to left shunt (n = 33),
      concomitant cardiac surgery (n = 26), surgeon preference (n = 7), and lack of
      transvenous access to the atrial endocardium (n = 6). Follow-up (median 23
      months; mean 28.0 +/- 23.1 months; range 1-78 months) data beyond 1 month
      postimplantation were available for 44 leads. Atrial sensing was > or = 2.0 mV
      for 26 leads (59%) with sensing possible at > or = 0.75 mV for 42 leads (95%).
      Threshold data were available at 5 V for 37 leads and at 2.5 V for 36 leads with
      mean pulse width thresholds measuring 0.21 +/- 0.33 ms and 0.34 +/- 0.34 ms,
      respectively. Two leads failed (high capture thresholds at 5 days [n = 1], lead
      fracture at 42 months [n = 1]; one of which was replaced. Four additional leads
      were replaced electively (marginal thresholds [n = 1], intermittent phrenic nerve
      stimulation [n = 1], damaged during subsequent surgery [n = 1], clinically
      irrelevant insulation break [n = 1]) concomitant with additional cardiac surgery.
      Until a commercially available lead is developed and released, improvisation with
      a bipolar active fixation endocardial lead as a bipolar epicardial atrial lead is
      a reasonable approach to providing bipolar atrial sensing and pacing in patients
      for whom endocardial pacing is contraindicated.

PMID- 9604243
TI  - Spontaneous reinitiation of atrial fibrillation following transvenous atrial
      defibrillation.
AB  - Spontaneous reinitiation of atrial fibrillation (AF) has not been systematically
      looked at in patients undergoing transvenous AF. This study involved 11 patients,
      the mean age 60 +/- 8 years, 3 male and 8 female, in whom transvenous atrial
      defibrillation successfully converted AF to sinus rhythm. Eight patients had
      paroxysmal AF and three patients had chronic persistent AF for 4 weeks or more.
      Four patients were taking antiarrhythmic medications at the time of testing.
      Multipolar transvenous catheters were positioned inside the coronary sinus, right
      atrium, and the right ventricle. Atrial defibrillation testing was performed
      using the METRIX atrial defibrillation system in nine patients and the Ventritex
      HVSO2 in the remaining two patients. A total of 64 therapeutic shocks (range 3
      11) were delivered in the 11 patients, and 31 of these successfully converted AF
      to sinus rhythm. In four patients spontaneous AF was reinitiated following 12
      successful transvenous atrial defibrillation episodes. The mean time to
      reinitiation of AF following shock delivery and restoration of sinus rhythm was
      8.26 +/- 5.25 seconds, range 1.8-19.9 seconds. All 12 episodes of spontaneous AF
      were preceded by a spontaneous premature atrial complex. The coupling interval of
      the premature atrial complexes was 443 +/- 43 ms, range 390-510 ms. None of the
      patients taking antiarrhythmic medications or those demonstrating no premature
      atrial complexes had spontaneous reinitiation of AF. In conclusion, spontaneous
      reinitiation of AF can occur in a significant proportion of patients with AF
      undergoing transvenous atrial defibrillation. This phenomenon is preceded by the
      occurrence of atrial premature complex. Findings of this study may have
      significant clinical implications.

PMID- 9604244
TI  - Importance of pacemaker noise reversion as a potential mechanism of pacemaker-ICD
      interactions.
AB  - Numerous types of interactions between pacemakers and implantable cardioverter
      defibrillators (ICDs) have been described. Pacemaker outputs preventing
      appropriate detection of ventricular tachycardia or ventricular fibrillation by
      the ICD is one of the more serious. Asynchronous pacemaker activity during
      ventricular arrhythmias may be caused by either nonsensing of the arrhythmia or
      by noise reversion, which is an algorithm that causes the pacemaker to switch to
      asynchronous pacing when repetitive sensing at a high rate occurs. We analyzed
      the mechanisms underlying asynchronous pacemaker activity in ventricular
      arrhythmias using pacemaker telemetry during the arrhythmia. Thirty-nine induced
      arrhythmias from 26 different procedures in 19 patients with both pacemakers and
      ICDs were analyzed. Of the 39 arrhythmias, asynchronous pacemaker activity
      occurred in 16. The underlying mechanism was nonsensing in 4 episodes and noise
      reversion in 12 episodes. Clinically significant interference with detection
      arose on three occasions. Conditions favoring the occurrence of noise reversion
      include specific pacemaker models, arrhythmia cycle lengths in the range causing
      noise reversion of the individual pacemaker model, long noise sampling periods,
      and VVI pacing mode. Noise reversion can be diagnosed by telemetering the
      pacemaker marker channel during ventricular arrhythmias as a part of routine
      pacemaker-ICD interaction evaluation. It can be prevented or minimized by
      programming short ventricular refractory periods or using pacemakers with short
      retriggerable refractory periods.

PMID- 9604245
TI  - Heart rate variability in passive tilt test: comparative evaluation of
      autoregressive and FFT spectral analyses.
AB  - The dynamic response of the autonomic nervous system during tilting is assessed
      by changes in the low (LF) and high frequency (HF) components of the RR series
      power spectral density (PSD). Although results of many studies are consistent,
      some doubts related to different methodologies remain. Specifically, the
      respective relevance of autoregressive (AR) and fast Fourier transform (FFT)
      methods is often questioned. Beat-to-beat RR series were recorded during 90
      degrees passive tilt in 18 healthy subjects (29 +/- 5 years, eight females). FFT
      based (50% overlap, Hanning window) and AR-based (Levinson-Durbin algorithm) PSDs
      were calculated on the same RR intervals. Powers in very low frequency (VLF: <
      0.04 Hz), LF (0.04-0.15 Hz), and HF (0.15-0.40 Hz) bands were calculated either
      by spectrum integration (FFT and ARIN), by considering the highest AR component
      in each band (ARHP), or by summation of all AR components (ARAP). LF and HF raw
      powers (ms2) were normalized by total power (%P) and by total power after removal
      of the VLF component (nu). AR and FFT total powers were not different, regardless
      of body position. In supine condition, when compared to ARHP and ARAP, FFT
      underestimated VLF and overestimated LF, whereas in tilt position FFT
      overestimated HF and underestimated LF. However, supine/tilt trends were
      consistent in all methods showing a clear reduction of HF and a less marked
      increase of LF. Both normalization procedures provided a significant LF increase
      and further magnified the HF decrease. Results obtained with ARIN were remarkably
      close to those obtained with FFT. In conclusion, significant differences between
      AR and FFT spectral analyses do exist, particularly in supine position.
      Nevertheless, dynamic trends provided by the two approaches are consistent.
      Normalization is necessary to evidence the LF increase during tilt.

PMID- 9604246
TI  - Rhythm management in atrial fibrillation--with a primary emphasis on
      pharmacologic therapy: Part 3.
AB  - Atrial fibrillation (AF) is the most common, sustained, symptomatic
      tachyarrhythmia that clinicians are called upon to manage. Management strategies
      include ventricular rate control coupled with anticoagulation, versus restoration
      and maintenance of sinus rhythm. Rate control may be achieved pharmacologically,
      with agents that impair AV nodal conduction directly and/or by increasing
      parasympathetic/sympathetic balance, or by modifying or ablating the AV nodal
      region anatomically. Rhythm control may be achieved by electrical or
      pharmacologic conversion followed by maintenance of sinus rhythm by pharmacologic
      (or occasionally ablative) therapies. This article will present current
      approaches to rate and rhythm control issues in atrial fibrillation. Parts 1 and
      2, published previously, dealt with rate control and with the restoration of
      sinus rhythm. Part 3, the current article, details the selection process of
      choosing a therapy to maintain sinus rhythm, including the likelihood of success,
      the risks of therapy, and individualization of therapy as dependent upon the
      nature of the structural heart disease present. It also discusses
      nonpharmacologic approaches that have been recently developed or are undergoing
      development. One suggested drug selection algorithm is provided.

PMID- 9604247
TI  - Adulterous tachycardia: what is the mechanism?

PMID- 9604248
TI  - Long-term memory monitoring in infant tachycardias.
AB  - Evaluation and detection of pathological tachycardias in infants sometimes is
      difficult. Noninvasive recording of the infant's ECG at the time of symptoms
      forms the mainstay of diagnosis, although invasive electrophysiological testing
      may be required. Accurate rhythm diagnosis is central to successful treatment.
      The advent of high capacity ambulatory memory monitoring makes it possible to
      record ECG signals, as well as apnea data. We present two cases of infant
      tachycardia studied by memory monitor. These devices yield good quality ECG
      signals and may provide information regarding a particular rhythm disturbance.

PMID- 9604249
TI  - One-to-two atrioventricular conduction causing nonreentrant tachycardia:
      successful treatment with radiofrequency ablation.
AB  - The anatomical substrate for AV nodal reentrant tachycardia (AVNRT) is well known
      and is due to anterograde conduction through a slow conducting pathway and
      retrograde conduction using a fast conducting pathway. In this report, we
      describe a patient with AVNRT who also presented with frequent episodes of
      paroxysmal nonreentrant tachycardia due to the occurrence of two conducted
      ventricular beats for each sinus depolarization. Palpitations and arrhythmias
      were abolished after radiofrequency ablation of the slow pathway.

PMID- 9604250
TI  - Radiofrequency catheter ablation of idiopathic left ventricular tachycardia
      originating in the left anterior fascicle.
AB  - Radiofrequency catheter ablation has been used to treat idiopathic left
      ventricular tachycardia with high success rates. The majority of reported cases
      have exhibited the typical findings of right bundle branch block morphology with
      left axis deviation and originate from within or near the left posterior
      fascicle. We report a case of idiopathic left ventricular tachycardia originating
      from within or near the left anterior fascicle, which was successfully ablated
      using a local Purkinje potential as a guide.

PMID- 9604251
TI  - Role of transesophageal echocardiography in the diagnosis of infected retained
      pacing lead.
AB  - A 68-year-old woman had a transvenous pacemaker implanted 6 years ago. One year
      after the procedure the pulse generator was removed due to generator site
      infection. Efforts to remove the lead resulted in fracture of the tip, which was
      abandoned in the right cardiac cavities. After this the patient suffered
      intermittent episodes of fever and chills, which responded to antibiotic therapy.
      At her recent admission, transesophageal echocardiography revealed a large mass
      attached to the free end of the fractured lead suggestive of the existence of a
      vegetation on the pacing lead. The diagnosis was confirmed at surgery.

PMID- 9604252
TI  - Pacemaker lead fracture due to twiddler's syndrome.

PMID- 9604253
TI  - Sotalol associated torsades de pointes tachycardia in a 15-month-old child:
      successful therapy with magnesium aspartate.
AB  - Torsades de points (Tdp) is a form of ventricular tachycardia, and its occurrence
      in childhood is very rare. In adult patients treated with sotalol, Tdp has been
      reported to the occur with an incidence of 2%-4%. In children who are treated
      with sotalol, occurrence of Tdp has been reported in only a single case. A 15
      month-old girl with Wolff-Parkinson-White syndrome developed recurrent syncopal
      attacks. She had been treated with sotalol 1.5 mg/kg daily since shortly after
      birth because of recurrent episodes of paroxysmal supraventricular tachycardia.
      ECG monitoring exhibited frequent Tdp tachycardia. Serum electrolyte levels were
      normal. Echocardiographic analysis excluded a structural heart defect and did not
      show any signs of myocardial infection. Sotalol treatment was stopped and an
      infusion with lidocaine was started. Despite this therapy the Tdp continued.
      Magnesium aspartate was then administered, which immediately stopped the Tdp. As
      no other reason was evident, Tdp in this child has to be judged as a
      proarrhythmia related to sotalol therapy.

PMID- 9604254
TI  - Unusual approach of a pacemaker electrode in a patient with a silent superior
      vena cava syndrome.
AB  - A man with a history of bilateral pectoral pocket infection and subsequent
      pacemaker implantation with a screw-in epicardial lead was referred because of
      increasing lead impedance. Venography revealed bilateral total occlusion of the
      subclavian and innominate veins with extensive collateral formation in this
      asymptomatic patient. Both internal jugular veins were also totally occluded.
      Because repeated pacemaker implantation using epicardial leads resulted in
      increasing lead impedance of the ventricular lead within 1 year after implant, an
      alternative approach was found using the superior caval vein with minimal
      invasive thoracotomy for single lead VDD pacing.

PMID- 9604255
TI  - Transiliac vein approach to a permanent pacemaker implantation after aortic valve
      reoperation.
AB  - This article describes the case of a 71-year-old woman in whom a permanent
      pacemaker implantation was performed through an iliac vein because of superior
      vena cava obstruction after aortic valve reoperation. During a 6-month follow-up,
      the patient did well and the pacemaker performance was satisfactory.

PMID- 9604256
TI  - Technical aspects of the CPI Vigor DR device.

PMID- 9604257
TI  - An implanted cardioverter defibrillator [ICD].

PMID- 9604258
TI  - A case-control study on bovine tuberculosis in the Veneto Region (Italy).
AB  - A case-control study was undertaken to provide information about the role of some
      husbandry practices and farm characteristics in the epidemiology of bovine
      tuberculosis in the Veneto Region. Twenty-seven breeding herds where a positive
      result to the single intradermal cervical tuberculin test was confirmed by post
      mortem examination were compared with seventy-four herds which had been free of
      the disease for at least three years. Epidemiological information was collected
      on farms. The factors taken into account in the study were chosen on the basis of
      their epidemiological plausibility and of the local livestock characteristics.
      Multiple logistic regression was applied to analyse the data. Factors identified
      as possibly involved in increasing the risk of bovine tuberculosis in the Veneto
      Region were the presence of mixed (dairy and beef) enterprises (OR = 4.9, P =
      0.001) and of cattle purchase (OR = 5.8; P = 0.003). Other factors (such as herd
      size, housing system, summer mountain pasture, possible contact with wild
      animals, and indirect contacts with other herds) did not appear to significantly
      contribute to tuberculosis presence in this area. The results of this case
      control study support the hypothesis that in the Veneto Region bovine
      tuberculosis infection is still associated with classical risk factors both
      (directly or indirectly) related to cattle movements.

PMID- 9604260
TI  - Qualitative interaction between the observer and the observed in veterinary
      epidemiology.
AB  - The phenomenon of qualitative interaction between the research activity and the
      studied object exists in veterinary epidemiology, as in all observation-based
      disciplines. Observational studies carried out under farm conditions strongly
      involve the farmers and the farm's usual advisors in the data collection. This
      leads to various biological and sociological interactions between the observer
      and the observed that can modify the results of the study. Some methodological
      considerations are proposed in order to consider such qualitative interaction,
      from the designing of the study through to the interpretation of the results.
      Examples are presented to illustrate these ideas.

PMID- 9604259
TI  - Milk production and reproduction during a subclinical bovine herpesvirus 1
      infection on a dairy farm.
AB  - This study describes an outbreak of bovine herpesvirus 1 (BHV1) infections in a
      dairy herd with special reference to disease symptoms, reproductive performance
      and milk production losses. The study was carried out with a dairy herd
      consisting of 98 lactating animals. All animals were housed in the same freestall
      barn with intensive contact between all animals. An outbreak of BHV1 was induced
      by injecting three seropositive cows with dexamethasone. During the outbreak, no
      clinical signs were observed in any of the newly infected animals. At the time of
      infection, a significant drop in milk production was noted in animals that were
      initially-seronegative. The production loss was estimated at approximately 9.5 1
      per infected animal during the infectious period of 14 days. None of the pregnant
      cows aborted because of BHV1 infection. During 50 days before BHV1 circulation,
      there was a significant decrease in the number of successful inseminations in
      both seronegative and seropositive animals. Therefore, it is doubtful that early
      pregnancies were terminated by BHV1 infection. The proportion of successful
      inseminations during the BHV1 circulation in this herd, and in the period
      thereafter, did not significantly differ from the baseline period.

PMID- 9604261
TI  - The dependence of kappa on attribute prevalence when assessing the repeatability
      of questionnaire data.
AB  - The objective of this paper was to illustrate the dependence of the kappa
      statistic on the underlying population prevalence of a measured outcome, and the
      related difficulties in interpreting kappa values for assessing the repeatability
      of survey data. An example was taken from a test-retest study of the
      repeatability of a questionnaire administered to dairy producers in Ontario,
      Canada. Ten producers completed two questionnaires, which contained numerous
      identical questions. Kappa was used to assess repeatability between the
      questionnaires for questions with responses which were measured on a dichotomous
      scale. The magnitude of the kappa statistic is shown to be a function of the
      prevalence of the trait measured by a question as well as the number of
      discordant responses.

PMID- 9604262
TI  - Risk factors for existence of Bovine Herpes Virus 1 antibodies on nonvaccinating
      Dutch dairy farms.
AB  - A more closed farming system may prevent introduction of infectious diseases on
      dairy farms and can be a good starting point for control of these diseases. Data
      were available on the presence of Bovine Herpes Virus 1 (BHV1) antibodies in bulk
      milk and/or blood samples of Dutch dairy farms. Furthermore, information about
      the possible risk factors for introduction of infectious diseases was collected
      on 214 of these dairy farms. Data of 107 farms which had been never vaccinated
      against BHV1 remained for the analysis. A positive BHV1 status on these 107 farms
      could only be caused by introduction of BHV1. Risk factors for introduction of
      BHV1 on the farms were quantified using logistic regression. BHV1-positive farms
      purchased cattle and participated in cattle shows more often compared with BHV1
      negative farms. A BHV1-positive farm also had more (professional) visitors in the
      barn who used farm clothing less often. The BHV1-positive farms were found to be
      situated closer to other cattle farms compared with the BHV1-negative farms.

PMID- 9604264
TI  - Design and implementation of the United States National Animal Health Monitoring
      System 1995 National Swine Study.
AB  - The United States Department of Agriculture's National Animal Health Monitoring
      System 1995 National Swine Study was designed to estimate management, health and
      productivity parameters on pig operations in the United States. Sixteen major
      swine-producing states that accounted for nearly 91% of June 1, 1995 swine
      inventory and nearly three-fourths of United States swine producers were included
      in the study. In the initial phase of the study, National Agricultural Statistics
      Service enumerators collected information from 1477 producers involved in all
      phases of swine production (farrowing, nursery, and grower/finisher). Of these,
      405 operations with > or = 300 finisher pigs (with at least one finisher pig > or
      = 54 kg) participated in the subsequent component of the study, which involved on
      farm visits by state and federal veterinary medical officers and animal health
      technicians, and which concentrated on the grower/finisher phase of production.
      Of those eligible to take part in the second phase of the study, participation
      was higher among independent producers (48.3%) than among contract producers
      (15.3%). Participation was also higher among operations that used advanced record
      keeping systems (such as record cards for individual breeding hogs or a computer
      based record-keeping system). Thus, study results could have been influenced by
      response biases. As a biosecurity measure, 40.5 +/- 2.1% of operations restricted
      entry to employees only. For operations that permitted non-employees to enter the
      premises, relatively few enforced other biosecurity measures on visitors (0.4 +/-
      0.1% required feed-delivery personnel and livestock handlers to shower before
      entering the premises; 3.3+/- 0.9% required a footbath; and 7.0 +/- 1.5% required
      feed-delivery personnel and livestock handlers not to have visited another
      operation with pigs on that day). The most common method of waste storage (used
      by 49.9 +/- 3.8% of operations with > or = 300 finisher pigs) was below-floor
      slurry or deep pit.

PMID- 9604263
TI  - Effect of controlling natural field-tick infestation on the growth of N'Dama and
      Gobra zebu cattle in the Gambia.
AB  - The effect of tick infestations on liveweight gain (LWG) was assessed by
      comparison of weight changes in flumethrin-treated N'Dama and Gobra zebu cattle
      (16-20 months old) with respective control groups submitted to natural tick
      challenge over 1 year. Flumethrin was applied monthly, fortnightly or weekly.
      Preventive treatments against anaplasmosis, babesiosis and trypanosomosis were
      given. Mortality rate was recorded and post-mortem examinations carried out. In
      both treated and control animals, significantly fewer Hyalomma spp. and Amblyomma
      variegatum were found on N'Dama than on Gobra zebu cattle. Both breeds are
      equally susceptible to Rhipicephalus senegalensis infestation. Total annual tick
      burdens did not cause significant differences in LWG between acaricide-treated
      and control cattle in either breeds. LWG was also not affected during or after
      the annual peak of tick infestation (composed mainly by A. variegatum and R.
      senegalensis). Equally-high mortality (35%), due to unidentified causes, was
      recorded in acaricide-treated and control Gobra cattle; mortality in N'Dama
      cattle was 7.5%. In both breeds, about the 90% of mortality occurred at the end
      of the dry season. Breed differences in tick burden confirm previous results. If
      tick-borne infections do not influence LWG or mortality, then it is concluded
      that intensive tick control is not justifiable in Gambian livestock.

PMID- 9604265
TI  - Word search performance for diagnoses of equine surgical colics in free-text
      electronic patient records.
AB  - The objectives of the current project were to: (1) identify limitations of search
      sensitivity and positive predictive value (PPV) for free-text surgical diagnoses
      included in electronic patient records maintained at the University of
      California, Davis, Veterinary Medical Teaching Hospital (VMTH), (2) develop
      procedural or programmable recommendations for removing these limitations, and
      (3) provide guidelines for effective search strategies for users performing
      aggregate searches using the VMTH clinical information system. Search sensitivity
      corresponds to detection sensitivity (the capacity of a search term to 'identify'
      a relevant document) and search PPV indicates the proportion of retrieved
      documents that are relevant. All horses submitted to the VMTH for a
      gastrointestinal (GI) disorder requiring surgical intervention in 1995 were
      identified using procedure codes for billing purposes and stored in the
      electronic patient record. Patient records and surgical reports were reviewed for
      causes of GI disorders, and variation in naming of these disorders. Key word
      searches were performed for four GI disorders, and search performance was
      evaluated by estimating search sensitivity and PPV. Search sensitivity ranged
      from 33% to 98%, and PPV ranged from 2% to 74%. The procedural recommendation
      that would likely have the greatest influence on minimizing these search
      limitations would be more uniform naming of GI disorders. This would free
      searchers from having to anticipate all of the exact word combinations that could
      be used in the relevant documents, and also minimize retrieval of irrelevant
      documents.

PMID- 9604266
TI  - Associations between behavioural indicators of "stress" in weaner pigs and
      respiratory lesions at slaughter.
AB  - The aim of the study was to investigate associations on the individual-pig level
      between eight behavioural indicators of 'stress' (defined in a very general
      sense), in seven to eight-week old piglets four weeks after weaning and the
      occurrence of atrophic rhinitis (AR) and chronic pleuritis (CP) at slaughter. The
      study was designed as a cohort study, including 512 pigs from two commercial
      farms. With one exception Actinobacillus pleuropneumoniae serotype 2 (App2)
      infection was not associated with any of the behaviour patterns observed. Using
      random-effects logistic regression, weak statistical associations, positive as
      well as negative, were found between the performance of several behaviour
      patterns and the two pathological lesions. This suggests the existence of
      biological associations between oral behaviour patterns in young pigs and the
      health status later in life. However, the results were not consistent between
      specific oral behaviour patterns or between the two herds indicating that the
      associations found are either due to chance or reflect the existence of herd
      specific confounders. Therefore, results based on studies within only one herd
      should not be generalized to other herds without care. Behavioural observations
      on seven- to eight-week-old piglets on the basis of the present investigation
      cannot be recommended for use as early predictors of AR or CP at slaughter.
      Further studies are needed in order to elucidate causal relations between
      behaviour and health.

PMID- 9604267
TI  - Herd size and sero-prevalence of Salmonella enterica in Danish swine herds: a
      random-effects model for register data.
AB  - The association between herd size and sero-prevalence of Salmonella was assessed
      in a random-effects model with herd size, county and date of slaughter as fixed
      effects. A total of 510,915 meat-juice samples from 14,593 herds located in 13
      counties in Denmark was included in the study. A random-effects model was
      developed from separate models for smaller strata of data from herds with
      approximately equal sizes. The combined model was analysed and the results
      reported. Herd size was positively associated with the sero-prevalence of
      Salmonella enterica, but the size of the association was biologically of little
      importance, because the within-herd and the between-herd variations were
      relatively large in comparison. The relative magnitudes of the variance
      components indicated that factors associated with both the herd level and the pig
      level could be important in the prediction of seroprevalence of S. enterica.

PMID- 9604268
TI  - Vietnamese trials with a thermostable Newcastle disease vaccine (strain I2) in
      experimental and village chickens.
AB  - The Australian I2 strain of Newcastle disease virus was tested as a vaccine in
      the laboratory and in Vietnamese villages. The infectivity litre of lyophilised
      vaccine fell less than 1 log10 unit on storage for 6 days at 26-32 degrees C.
      Vaccine stored at similar temperatures induced high levels of immunity in
      laboratory chickens after storage for 17 days and in village chickens after
      storage for 21 days. I2 vaccine protected for at least 24 weeks after
      vaccination, and for 16 weeks after application in drinking water. Under
      laboratory conditions, I2 vaccine given by eye drop spread by contact to
      unvaccinated chickens, inducing in them both an antibody response and protective
      immunity. In villages, chickens vaccinated by eye drop, chickens receiving
      vaccine on food and chickens in contact with vaccinated chickens all resisted
      artificial challenge 6 weeks after vaccination. There were no adverse reactions
      to vaccination. Strain I2 was judged to be thermostable, avirulent and
      immunogenic, and suitable for use as a vaccine under village conditions.

PMID- 9604269
TI  - Biannual anthelmintic treatments in village Djallonke sheep in The Gambia:
      effects on productivity and profitability.
AB  - An on-farm deworming trial was conducted between 1991 and 1995 on traditionally
      managed Djallonke sheep in The Gambia to assess the impact on productivity and
      profitability of prophylactic biannual anthelmintic treatments- Fifteen private
      flocks with an average of 25 animals per flock participated in the experiment.
      Half of each flock was dewormed twice a year while the other half served as the
      control group. The two productivity traits that were significantly improved by
      the treatment scheme tested were the number of lambs per lambing which increased
      from 1.11 +/- 0.31 (Mean +/- S.D.) to 1.19 +/- 0.39 and the number of lambings
      per year which improved from 1.04 +/- 0.53 to 1.22 +/- 0.47. The mortality and
      weight at 12 months were not significantly affected by the treatment. Monitoring
      of sheep sales in the flocks and on surrounding markets allowed the calculation
      of a rate of return to the treatment scheme tested of 246%. Despite large
      variations in returns. The scheme studied is recommended as over 90% of the
      adopting farmers would yield positive returns to their investment.

PMID- 9604270
TI  - Risk factors for infection with verocytotoxigenic Escherichia coli in cattle on
      Ontario dairy farms.
AB  - Risk factors for prevalent infection with verocytotoxigenic Escherichia coli
      (VTEC) were studied in a random sample of 886 cows and 592 calves under 3 months
      of age on 80 randomly selected dairy farms in southern Ontario. Fecal-culture
      supernatants from each animal were screened for verocytotoxicity using a Vero
      cell assay (VCA) and for verocytotoxin (VT) genes by a polymerase chain reaction
      (PCR) procedure. Up to 20 F. colt isolates from positive samples were tested for
      VT production using VCA and PCR. VTEC isolates were serotyped. Farm managers were
      interviewed using a standardized questionnaire to obtain information on farm- and
      individual animal-level management practices and characteristics. There was a
      significant (P < 0.001) positive association between age of calves and their VTEC
      infection status, and calves were significantly more likely to be infected than
      cows. The proportion of calves infected on the farm was positively associated
      with both the use of regular pails for feeding calves (as opposed to nipple
      bottles or nipple pails) and bringing new animals into the herd in the previous
      year.

PMID- 9604271
TI  - Ten-year survival of Finnish lower limb amputees.
AB  - Data on mortality for the ten years following lower limb amputation were obtained
      from all the 16 surgical units in Southern Finland and the National Social
      Insurance Institution. In Southern Finland during the period 1984-1985,
      amputations of the lower limb were performed on 705 patients, of whom 382 (54%)
      were women and 323 (46%) men. The majority of the amputations, 47% were performed
      for vascular diseases and 41% were performed for diabetes mellitus. The overall
      survival was 62% at one year after amputation, 49% at two years, 27% at five
      years and 15% at ten years. The median survival after amputation was 1 yr 5 mth
      for the women and 2 yr 8 mth for the men. Of the arteriosclerotics, 43% died
      within one postoperative year while 43% lived longer than two years and 23%
      longer than five years. The median survival of arteriosclerotics was 1 yr 6 mth.
      The corresponding figure for patients with diabetes was 1 yr 11 mth. Of the
      diabetics, 38% died within one postoperative year while 47% lived longer than two
      years and 20% longer than five years. Of the trauma patients, 86% lived longer
      than five years and 71% longer than ten years. Of the trans-femoral amputees, 54%
      lived longer than one year, 36% over two years, 18% over five years and 8% over
      ten years. The corresponding figures for trans-tibial amputees were 70%, 53%, 21%
      and 4%. Many elderly vascular and diabetic patients undergoing amputation have a
      reduced physiological reserve and high mortality. The more proximal the
      amputation, the greater the risk that the patient will never be able to walk or
      that the duration of use of the prosthesis will be short. If a prosthesis seems
      to be a reasonable option for the elderly amputee, any delays in prosthetic
      fitting should be avoided in older age groups.

PMID- 9604272
TI  - Three dimensional measurements of pelvic tilt in trans-tibial amputations: the
      effects of pelvic tilt on trunk muscles strength and characteristics of gait.
AB  - The aim of this study was to determine the degree of pelvic tilt in the three
      dimensions, the trunk muscle strength and effects on gait in trans-tibial
      amputated patients. This study comprised of 22 unilateral trans-tibial amputated
      patients who were seen at the authors' Prosthetics and Orthotics Laboratory for
      the purpose of prosthetic provision. Measurements were made using plurimeter and
      caliper and gait observations were made by video camera. In the sagittal and
      horizontal planes respectively the pelvic tilt was measured to be 12 degrees and
      5.73 degrees, and such measurements in relation to the trunk extensor and flexor
      muscles were shown to be statistically significant (p < 0.05). On the contrary,
      the same could not be said for frontal plane measurements. In addition, in 9
      cases excessive knee flexion was noted during the stance phase having a direct
      influence on the pelvic tilt (p < 0.05).

PMID- 9604273
TI  - Biomedical gait evaluation of the immediate effect of orthotic treatment for
      flexible flat foot.
AB  - Flexible flat foot subjects attending the prosthetics and orthotics units come
      with prescriptions from orthopaedic surgeons for arch supports. Usually a pair of
      thermoformed plastic inserts are fabricated and fitted to treat the patients.
      However the effect of the orthotic treatment is not yet clear. A motion analysis
      system with two video cameras placed on the lateral and rear sides of the subject
      together with one force platform was used to investigate the immediate effects of
      the orthotic treatment. The force platform collected force data and the two
      cameras captured two-dimensional displacement data of the lower limb. Eight
      subjects, all having an arch index (AI) larger than 3.0 participated in the
      study. For each subject, three successful steps on the force platform were
      videotaped for both the shod (with shoe only) and the orthotic (with shoe and
      orthosis) conditions. The kinetic variables were normalized to individual body
      weight and averaged for each subject. A Paired t-test was conducted to analyse
      sample means of matched pairs between the shod and the orthotic conditions. The
      results showed changes in displacement data with relatively little change in the
      collected force data. The modified UCBL shoe insert evaluated significantly
      affected the orientation and movements of the subtalar joint, ankle joint and
      knee joint. These immediate effects reduced the degree and duration of abnormal
      pronation during the stance phase and thus had the potential for decreasing
      strain in the plantar ligaments and reducing abnormal tibial rotation which may
      be therapeutic for the foot.

PMID- 9604274
TI  - Primary metatarsalgia: the influence of a custom moulded insole and a rockerbar
      on plantar pressure.
AB  - The effects of a custom moulded insole and a rockerbar on peak pressure and force
      impulse as well as on pain scores in subjects with a history of metatarsalgia
      were studied. In addition the subjects' preference for the type of intervention
      was determined. Forty-two subjects with a history of primary metatarsalgia were
      selected. They were all provided with the same brand of extra depth shoes with a
      ready made insole. The effect of custom moulded insoles, a rockerbar and the
      interaction between the two interventions were studied by testing the four
      possible combinations: ready made insole without a rockerbar, ready made insole
      with a rockerbar, custom moulded insole without a rockerbar and custom moulded
      insole with rockerbar. At the most important region, the central distal forefoot,
      a rockerbar caused a decrease in force impulse of 15.1% and a decrease in peak
      pressure of 15.7%. The custom moulded insole produced a decrease of 10.1% in
      force impulse and of 18.2% in peak pressure. Pain scores were significantly lower
      for interventions with a custom moulded insole, while the rockerbar showed no
      influence on pain scores. Subjects with pain preferred a custom moulded insole
      more often than subjects without pain. Decrease of peak pressure or force impulse
      was not correlated to pain scores. The use of either a custom moulded insole or a
      rockerbar produced an important decrease of peak pressure and force impulse at
      the central distal forefoot and, therefore, either is suitable in any situation
      which a decrease of pressure is vital.

PMID- 9604275
TI  - Test apparatus for the measurement of the flexibility of ankle-foot orthoses in
      planes other than the loaded plane.
AB  - Previous publications have reported on the flexibility of ankle-foot orthoses
      (AFO) only in the same plane as the applied load. This paper reports on a test
      apparatus developed to detect the flexibility of an AFO in 5 degrees of freedom
      when subjected to a plantar/dorsiflexion moment, a medial/lateral moment or a
      torque. A moment applied to an AFO in one plane induces angulation and
      translation in all planes.

PMID- 9604276
TI  - Biomechanical evaluation of the Milwaukee brace.
AB  - Although, the history of orthotic treatment for idiopathic scoliosis goes back
      more than fifty years, the mechanism of curve control by spinal orthosis is still
      controversial. Hypothetical explanations have been provided but few, if any, have
      been tested clinically. This study aims at the biomechanical evaluation of a
      spinal orthosis (Milwaukee brace) in order to improve understanding about the
      mechanism of curves control in orthotic movement. From the results of the study,
      the change of the interface pressure between the patient's body and thoracic pad,
      and the tension of the thoracic strap were highly correlated (r = 0.84) as
      patients performed different lying postures and daily activities. Lying on the
      thoracic pad is found to have the highest correctional force among different
      lying postures that may be favourable for preventing curve deterioration. The
      findings indicate that an increase in tension of the thoracic strap will increase
      the interface pressure on the thoracic pad and thus increase the resultant force
      exerted on the patient's body by the thoracic pad. Care must be taken as an
      excessive strap tension will increase discomfort and restrict body shifting
      exercises. The results also suggest that in scoliosis with thoracic lordosis, a
      short outrigger (small pulling angle of the thoracic strap) should be used as it
      will decrease the anteriorly directed force component so as to prevent
      exaggerating the thoracic lordosis.

PMID- 9604277
TI  - Seated-popliteal weight bearing prosthesis for a bilateral amputee.
AB  - Bilateral lower limb amputees suffer from a lack of stability when seated without
      prostheses due to lack of ground reaction forces through the stumps. In patients
      for whom ambulation is not a realistic goal, the seated-popliteal weight bearing
      prosthesis provides a solution for stability when seated in a wheelchair, without
      the problem of tibial pressure experienced with patellar-tendon-bearing
      prostheses.

PMID- 9604278
TI  - Toxins of Amanita phalloides.
AB  - The most poisonous mushroom toxins are produced by Amanita phalloides (death
      cap). The occurrence and chemistry of three groups of toxins (amatoxins,
      phallotoxins and virotoxins) are summarized. The concentration and distribution
      of toxins in certain species are variable, with the young fruit body containing
      lower, and the well-developed fungus higher concentrations, but there is a high
      variability among specimens collected in the same region. Regarding phallotoxins,
      the volva (the ring) is the most poisonous. The most important biochemical effect
      of amatoxins is the inhibition of RNA polymerases (especially polymerase II).
      This interaction leads to a tight complex and the inhibition is of a non
      competitive type. Non-mammalian polymerases show little sensitivity to amanitins.
      The amatoxins cause necrosis of the liver, also partly in the kidney, with the
      cellular changes causing the fragmentation and segregation of all nuclear
      components. Various groups of somatic cells of emanation resistance have been
      isolated, including from a mutant of Drosophila melanogaster. The phallotoxins
      stimulate the polymerization of G-actin and stabilize the F-actin filaments. The
      interaction of phallotoxins occurs via the small, 15-membered ring, on the left
      side of the spatial formula. The symptoms of human poisoning and the changes in
      toxin concentrations in different organs are summarized. Conventional therapy
      includes: (1) stabilization of patient's condition with the correction of
      hypoglycaemia and electrolytes; (2) decontamination; and (3) chemotherapy with
      different compounds. Finally, certain antagonists and protective compounds are
      reviewed, bearing in mind that today these have more of a theoretical than a
      practical role.

PMID- 9604279
TI  - Present of a toxin in the salivary glands of the marine snail Cymatium
      intermedius that targets nicotinic acetylcholine receptors.
AB  - Presence of a toxin in the salivary glands of the marine snail Cymatium
      intermedius that targets nicotinic acetylcholine receptors. Toxicon 36, 25-29,
      1998.-We present evidence of a neurotoxin from the salivary glands of Cymatium
      intermedius that displays acetylcholine-like effects on vertebrate (mouse ileum)
      and invertebrate (molluscan smooth muscle; molluscan heart; leech body wall)
      tissues. These effects were completely blocked by (+)-tubocurarine (10-100 muM)
      but not by atropine (up to 200 muM) suggesting that the toxin targets nicotinic
      like acetylcholine receptors. This affirms the proposal that this genus may
      overcome their prey with a paralytic secretion.

PMID- 9604280
TI  - Isolation, characterization and biological properties of two kinin-like peptides
      (peptide-S and peptide-r) from Scaptocosa raptoria venom.
AB  - Two peptides with kinin-like biological properties were isolated by
      chromatography on a Sephadex G-10 column followed by high-performance liquid
      chromatography, from the venom of the spider Scaptocosa raptoria. The isolated
      peptides (peptide-S and peptide-R) were shown to cause contraction on the
      isolated guinea-pig ileum at amounts equivalent to those shown by bradykinin.
      Both peptides relaxed the isolated rat duodenum, increased the capillary
      permeability, caused decreasing and biphasic effect of the arterial blood
      pressure in conscious rats and induced oedema in the rat paw. The peptides had
      activity and structural similarities to other peptides (kinin-like) isolated from
      venoms. The complete amino acid analysis gave peptide-S a structure with 36 amino
      acid residues and peptide-R 22 amino acid residues. The mol. wts were estimated
      to be in the range of 4000 and 2870, respectively.

PMID- 9604281
TI  - Identification and characterization of novel sodium channel toxins from the sea
      anemone Anthopleura xanthogrammica.
AB  - Six new toxins from the sea anemone Anthopleura xanthogrammica were identified
      using a molecular biological approach. Five of these novel isoforms resemble the
      47 residue type I long polypeptides native to Anthopleura elegantissima,
      Anthopleura fuscoviridis and Anemonia sulcata, while one appears to be chimera of
      the two previously identified 49 residue toxins native to A. xanthogrammica. Four
      of these toxins were expressed in bacteria, purified and characterized by ion
      flux assays in RT4-B and N1E-115 cell lines expressing the cardiac and neuronal
      Na channel isoforms, respectively. The novel 47 residue toxin isoforms form a new
      subclass within the A. xanthogrammica neurotoxin family, although they are
      related to previously described anemone toxins. One of the three 47 residue
      toxins characterized, PCR2-10, enhances veratridine-dependent sodium uptake,
      displaying a K0.5 of 329 nM and 1354 nM in RT4-B and N1E-115 cell lines,
      respectively. The novel 49 residue toxin, PCR3-7, interacts with the sodium
      channel with even higher affinity, enhancing sodium uptake with a K0.5 of 47 nM
      and 108 nM in RT4-B and N1E-115 cells, respectively.

PMID- 9604282
TI  - Inhibition of habutobin activities by habu antivenom.
AB  - This study investigated whether habu antivenom inhibits the clotting activity of
      habutobin, a thrombin-like enzyme from Trimeresurus flavoviridis venom. Habu
      antivenom, which is available as a commercial antibody against the crude venom of
      T. flavoviridis, has been used to treat envenoming by T. flavoviridis (the habu
      snake). The present study was undertaken to determine whether habu antivenom
      inhibits the activities of habutobin, which involve digestion of the A alpha
      chain and release of fibrinopeptide A (FPA) in rabbit fibrinogen. The results of
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated that habu
      antivenom inhibited the habutobin-induced digestion of the A alpha chain in
      rabbit fibrinogen. The results of FPA measurements using competitive enzyme
      linked immunoassay (CELIA) revealed that habu antivenom inhibited the release of
      FPA from rabbit fibrinogen induced by habutobin. In addition, a correlation was
      noted between the digestion of the A alpha chain and release of FPA from rabbit
      fibrinogen. Analysis of the inhibition kinetics of habu antivenom against the
      habutobin activity yielded a competitive double-reciprocal plot.

PMID- 9604283
TI  - Some pharmacological studies of venom from the inland taipan (Oxyuranus
      microlepidotus).
AB  - The present study was designed to obtain a basic pharmacological profile of venom
      from the inland taipan (Oxyuranus microlepidotus). Venom (0.05-50 micrograms/ml)
      produced dose-dependent contractions in guinea-pig ileum, which could not be
      reproduced upon second administration. The cyclooxygenase inhibitor indomethacin
      (1 microM), a preceding anaphylactic response induced by egg albumin and
      inactivation of phospholipase A2 (PLA2) by incubation with 4-bromophenacyl
      bromide (1.8 mM) all significantly inhibited responses to venom (0.5
      micrograms/ml). Venom (0.5 micrograms/ml) caused inhibition of stimulation
      induced contractions in the prostatic segment of rat vas deferens which was not
      significantly affected by the alpha 2-adrenoceptor antagonist idazoxan (0.3
      microM). Venom (10 micrograms/ml) caused time-dependent inhibition of the rat
      electrically stimulated phrenic nerve-diaphragm preparation, positive inotropic
      and chronotropic responses in rat isolated atria and relaxation in rat
      endothelium-denuded and -intact isolated aortae. In endothelium-intact aortae,
      the nitric oxide synthase inhibitor N-nitro-L-arginine (NOLA, 0.1 mM)
      significantly inhibited the response to venom (10 micrograms/ml). Venom (50
      micrograms/kg, i.v.) caused an immediate drop in blood pressure followed by
      cardiovascular collapse in anaesthetised rats. Venom (10 micrograms/kg, i.v.)
      caused a gradual fall in blood pressure which was sometimes accompanied by a
      temporary cessation of respiration. A PLA2 assay detected the presence of PLA2 in
      the venom. These results suggest that the venom contains a component capable of
      causing the synthesis of arachidonic acid metabolites and a component capable of
      relaxing vascular smooth muscle. The inhibitory effect on the phrenic nerve
      diaphragm is probably due to the previously identified neurotoxin (paradoxin).

PMID- 9604284
TI  - The three-dimensional structures of two toxins from snake venom throw light on
      the anticoagulant and neurotoxic sites of phospholipase A2.
AB  - The three-dimensional structures of the class II anticoagulant phospholipase A2
      (PLA2) toxin RVV-VD from the venom of Russell's viper, Vipera russelli russelli,
      and the class I neurotoxic PLA2 Notechis II-5 from the, Australian tiger snake,
      Notechis scutatus scutatus, were determined to 2.2 A and 3.0 A resolution,
      respectively. Both enzymes are monomeric and consist of 121 and 119 residues,
      respectively. A comparison of ten class I/II PLA2 structures showed, among other
      differences, that the beta-sheet of these enzymes (residues 76-83) is about 90
      degrees less twisted in class I than in class II PLA2s. This, along with the
      insertion of some residues in the region 57-59 in class I enzymes (the elapid
      loop), could be the main reason for the significant difference in the
      anticoagulant and (presynaptic) neurotoxic properties between the two classes of
      PLA2. It seems apparent from sequence and structural comparisons that the toxic
      site of PLA2 responsible for the strong anticoagulancy of these toxins consists
      of a negatively charged part, Glu53, together with a positively charged ridge of
      lysine residues free for intermolecular interactions. These lysines differ
      between the two classes of PLA2.

PMID- 9604285
TI  - Pharmacokinetics of 125I-labelled Walterinnesia aegyptia venom and its
      distribution of the venom and its toxin versus slow absorption and distribution
      of IGG, F(AB')2 and F(AB) of the antivenin.
AB  - A three-compartment open pharmacokinetic model best fitted the data obtained
      following the i.v. injection of the venom, toxin and the immunoglobulin fractions
      into either rabbits or mice. The venom and toxin, however, possessed
      pharmacokinetic characteristics that were significantly different from the
      immunoglobulin fractions. The venom and toxin had very highly significantly
      greater disposition rate constants to the shallow and deep tissue compartments
      and overall elimination rate constant from the central compartment than any of
      the immunoglobulin fractions. This was reflected in other pharmacokinetic
      parameters, including highly significantly smaller areas under the curve (AUC)
      and highly significantly greater volumes of the central compartment (Vc), shallow
      tissue compartment (Vt shallow), deep tissue compartment (Vt deep) and total body
      clearance (TBC). In rabbits, F(ab')2 possessed the fastest disposition rate
      constants and the shortest distribution half-lives, while Fab showed the slowest
      disposition rate constants and the longest distribution half-lives. The same
      picture occurred in mice except that the values for Fab were between those of
      F(ab')2 and IgG. The time needed by the venom and toxin to reach maximum tissue
      concentration (tmax) ranged between 7 and 15 min and 60 and 180 min for the
      shallow and deep tissue compartments, respectively. The immunoglobulin fractions
      required 8-26-fold these times to attain tmax; F(ab')2 was the fastest to achieve
      its maximal concentration. Following i.m. injection, very fast absorption of
      venom and toxin took place, with the toxin reaching tmax within 5-20 min and 90%
      of the injected dose absorbed within 60 min. The bioavailability factor (F) was
      0.82 and 0.88 for the venom and toxin, respectively. Fab had an F-value of 0.36
      and required 4.3 and 47.4-fold the time taken by the venom and toxin to achieve
      tmax. The calculated values of F for F(ab')2 and IgG were 0.25 and 0.26,
      respectively. In the physiologically based pharmacokinetics (PBPK), the venom and
      toxin reached tmax in the different organs studied very rapidly while the
      immunoglobulin fractions required several-fold this time to attain tmax. F(ab')2
      possessed the highest CPmax, the smallest AUC and the shortest t1/2 beta in the
      different tissues; Fab had values between F(ab)2 and IgG. It is concluded that
      F(ab')2 possesses pharmacokinetic characteristics that render it most suitable
      for use in serotherapy of snake and scorpion envenoming. It should be injected
      i.v. in doses higher than calculated neutralizing doses to compensate for the
      slow rate of distribution. Because of slow and incomplete absorption, the i.m.
      injection of the immunoglobulin fractions would be of little value in
      serotherapy.

PMID- 9604286
TI  - Characterisation of the effects of depolarising toxins on nerve terminal action
      potentials: apparent block of presynaptic potassium currents.
AB  - Previous studies showed that toxic phospholipases A2 (Pa-8 and Pa-10F) from the
      venom of Pseudechis australis, the Australian king brown snake, reduced
      acetylcholine release at mouse neuromuscular junctions and depressed motor nerve
      terminal action potentials [Fatehi et al. (1994a), Toxicon 32, 1559-1572], and it
      was postulated that these toxins induced their effect on the action potential
      waveforms through nerve terminal depolarisation. To test this hypothesis, the
      effects of Pa-11 (another phospholipase A2 from the venom of Pseudechis
      australis), and the known depolarising agents. myotoxin a, from the venom of the
      rattlesnake. Crotalus viridis viridis, and ouabain on these waveforms were
      compared with the changes induced in the nerve terminal action potentials by Pa-8
      and Pa-10F. The experiments were performed on the isolated mouse triangularis
      sterni preparation, using extracellular recordings. Pa-11 (0.1 microM) decreased
      the component of nerve terminal action potential related to Na+ and K+ currents
      to about 80% and 40% of control, respectively, after 60 min. Myotoxin alpha (5
      microM) and ouabain (50 microM) produced similar, time-dependent changes in the
      nerve terminal action potential. These effects are similar to those produced by
      Pa-8 and Pa-10F, and are consistent with a slow but partial loss of membrane
      potential at the nerve terminal. In addition, whole-cell patch-clamp recording
      was employed to investigate possible direct actions of Pa-8. Pa10F and Pa-11 on
      Na+ and K+ currents in NG108 and PC12 cells in culture. None of these toxins (0.8
      microM) reduced the Na+ and K+ currents in these cells. There was also no
      displacement of [125I]alpha-dendrotoxin bound to voltage-sensitive potassium
      channels on rat synaptosomal membranes induced by Pa-8, Pa-10F and Pa-11 (up to
      100 microM). These results support the hypothesis that the alteration of nerve
      terminal waveforms by these toxic phospholipases A2 is mediated by nerve terminal
      depolarisation.

PMID- 9604287
TI  - Characterization of a fibrinogen-clotting enzyme from Trimeresurus stejnegeri
      venom, and comparative study with other venom proteases.
AB  - Trimeresurus stejnegeri venom which contains TSV-PA (a specific plasminogen
      activator sharing 60-70% sequence homology with venom fibrinogen-clotting
      enzymes), also possesses fibrinogen-clotting activity in vitro. A fibrinogen
      clotting enzyme (stejnobin) has been purified to homogeneity by gel filtration
      and ion-exchange chromatography on a Mono-Q column. It is a single-chain
      glycoprotein with a mol. wt of 44,000. The NH2-terminal amino acid sequence of
      stejnobin shows great homology with venom fibrinogen-clotting enzymes and TSV-PA.
      Like TSV-PA, stejnobin was able to hydrolyse several chromogenic substrates.
      Comparative study of substrate specificities of stejnobin and other venom
      proteases purified in our laboratory was carried out on five chromogenic
      substrates. Stejnobin clotted human fibrinogen with a specific activity of 122
      NIH thrombin-equivalent units/mg protein. However, stejnobin did not act on other
      blood coagulation factors, such as factor X, prothrombin and plasminogen.
      Diisopropyl fluorophosphate and phenylmethanesulfonyl fluoride inhibited its
      activity, whereas ethylenediamine tetracetic acid had no effect on it, indicating
      that it is a serine protease. Although stejnobin showed strong immunological
      cross-reaction with polyclonal antibodies raised against TSV-PA, it was
      interesting to observe that, unlike the case of TSV-PA, these antibodies did not
      inhibit the amidolytic and fibrinogen-clotting activities of stejnobin.

PMID- 9604288
TI  - Effects of Pallas' viper (Agkistrodon halys pallas) venom on blood coagulation
      and characterization of a prothrombin activator.
AB  - The action of Pallas' viper (Agkistrodon halys pallas) venom on blood coagulation
      was examined in vitro and a strong anticoagulant effect was observed. This action
      was abolished after treatment with a specific inhibitor of phospholipase A2
      activity (p-bromophenacyl bromide), revealing a procoagulant action in low
      concentrations of treated venom (around 1 microgram/ml). The effect of the venom
      on haemostasis was further characterized by measuring its ability to activate
      purified blood coagulation factors. It is concluded that A. halys pallas venom
      contains prothrombin activation activity. A prothrombin activator (aharin) was
      purified from the venom by Sephadex G-75 gel filtration and ion-exchange
      chromatography on a Mono-Q column. It consisted of a single polypeptide chain,
      with a mol. wt of 63,000. Purified aharin possessed no amidolytic activity on
      chromogenic substrates. It did not act on other blood coagulation factors, such
      as factor X and plasminogen, nor did it cleave or clot purified fibrinogen. The
      prothrombin activation activity of aharin was readily inhibited by
      ethylenediamine tetracetic acid (a metal chelator), but specific serine protease
      inhibitors such as diisopropyl fluorophosphate and phenylmethanesulfonyl fluoride
      had no effect on it. These observations suggest that, like those prothrombin
      activators from Echis carinatus and Bothrops atrox venoms, the prothrombin
      activator from A. halys pallas venom is a metalloproteinase.

PMID- 9604289
TI  - Variability of bothrojaracin isoforms and other venom principles in individual
      jararaca (Bothrops jararaca) snakes maintained under seasonally invariant
      conditions.
AB  - Bothrojaracin (BJC) is a potent thrombin inhibitor isolated from the venom of
      Bothrops jararaca. Venoms from individual snakes have been shown to vary in BJC
      content, and more than one molecular variant (isoform) has been identified in the
      same venom. In order to determine whether the production of this protein and its
      isoforms varies under seasonally invariant conditions, an analysis was made of
      BJC isolated from venoms collected individually once a month for 10 months from
      two female B. jararaca snakes kept under conditions of constant temperature and
      photoperiod. The crude venom from each individual snake exhibited a
      characteristic pattern of protein bands on sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis (SDS-PAGE), with no noticeable variation throughout the
      collecting period. BJC from individual venoms was purified by gel filtration on
      Sephacryl S-200 followed by an affinity column (PPACK-thrombin Sepharose). BJC
      content and other activities such as phospholipase A2, azocaseinolytic activity
      and inhibition of thrombin-induced platelet aggregation varied considerably among
      the samples. Purified BJC from both snakes inhibited fibrin coagulation and
      migrated as a single band of 27,000 mol. wt on SDS-PAGE. However, the BJC pattern
      on non-denaturing PAGE differed between the two snakes, with four to six bands
      per sample each month, which were all recognized by polyclonal anti-BJC
      antibodies. The isoelectric focusing pattern of BJC was also characteristic for
      each snake, with only minor differences throughout the collecting period. These
      results indicate that under seasonally invariant conditions: (1) there was a
      considerable variation over the 10-month period in the production of BJC and
      other important venom activities such as phospholipase A2 and proteinases; (2)
      individual B. jararaca snakes produced a distinctive array of BJC isoforms; and
      (3) despite quantitative differences, there were essentially no qualitative
      differences in the production of BJC isoforms by individual snakes during the 10
      month period.

PMID- 9604290
TI  - The role of ionic strength on the enhancement of the hemolytic activity of
      sticholysin I, a cytolysin from Stichodactyla helianthus.
AB  - Sticholysin I (St I) is a potent cytolytic polypeptide purified from the
      Caribbean sea anemone Stichodactyla helianthus. The hemolytic activity of
      sticholysin is potentiated by its preincubation at high ionic strengths. In the
      present work the mechanism of the potentiating action of the medium ionic
      strength on the toxin hemolytic capacity is investigated. It is suggested that
      preincubation with high saline concentration induces a transition of St I to a
      more relaxed conformation that facilitates the lytic process.

PMID- 9604291
TI  - The fate and acute toxicity of aflatoxin B1 in the mastomys and rat.
AB  - The fate and acute toxicity of aflatoxin B1 (AFB1) were studied in the mastomys
      (Praomys coucha) and compared with Fischer rats. The experiment regarding the
      fate of [3H]AFB1 showed that the radioactivity was excreted mainly through the
      feces, more rapidly in the mastomys than in the rat, regardless of whether
      [3H]AFB1 was given orally or intravenously. The levels of radioactivity bound to
      the liver DNA were lower in the mastomys than in the rat, indicating that the
      levels of AFB1 binding to the macromolecules in the liver were lower in the
      mastomys. Consistent with such differences in the fate of AFB1 between the two
      species, the mastomys were far more resistent to the acute effects of AFB1 than
      were the rats. Oral administration of AFB1 at a dose of 1.0 mg/kg to rats caused
      marked microscopic changes in the liver, involving hepatic necrosis and
      proliferation of bile ducts, but at a dose of 4.0 mg/kg to mastomys caused no
      pathological changes in the liver or kidneys, and at a dose of 10.0 mg/kg caused
      only glycogen deposition in hepatic cells in a limited area. The observed
      differences in susceptibility to the toxic effects of AFB1 and in the fate of
      AFB1 between the two species are in accord with our previous finding that liver
      cytosol in the mastomys inhibits microsome-mediated AFB1-DNA binding in vitro
      more strongly than in rat liver.

PMID- 9604293
TI  - Okadaic acid production from the marine dinoflagellate Prorocentrum belizeanum
      Faust isolated from the Belizean coral reef ecosystem.
AB  - A species of epiphytic Prorocentrum (Dinophyta, Prorocentrales, collected from
      the macroalga Dictyota dichotoma, was brought into culture. Based on
      morphological characteristics, this isolate was identified as Prorocentrum
      belizeanum. Analysis of the culture extract using high-performance liquid
      chromatography and liquid chromatography-mass spectrometry indicated the
      production of okadaic acid, a toxic polyether linked with the human diseases,
      diarrhetic shellfish poisoning and ciguatera fish poisoning.

PMID- 9604292
TI  - Polybitoxins: a group of phospholipases A2 from the venom of the neotropical
      social wasp paulistinha (Polybia paulista).
AB  - The neotropical wasp Polybia paulistinha is very aggressive and endemic in south
      east Brazil, where it frequently causes stinging accidents. By using gel
      filtration on Sephadex G-200, followed by ion-exchange chromatography on DEAE
      Cellulose under a pH gradient, a group of four toxins (designated as polybitoxins
      I, II, III and IV) presenting phospholipase A2 (PLA2) activities was purified.
      These toxins are dimeric with mol. wts ranging from 115,000 to 132,000 and formed
      by different subunits. The four toxins contain very high sugar contents attached
      to their molecules (22-43% w/w) and presented different values of pH optimum from
      7.8 to 9.0; when dissociated, only residual catalytic activities were maintained.
      The catalytic activities of polybitoxins (from 18 to 771 mumoles/mg per minute)
      are lower than that of PLA2 from Apis mellifera venom and hornetin from Vespa
      basalis. The polybitoxins presented a non-linear steady-state kinetic behavior
      for the hydrolysis of phosphatidylcholine at pH 7.9, compatible with the negative
      co-operativity phenomena. All of the polybitoxins were very potent direct
      hemolysins, especially the polybitoxins-III and IV, which are as potent as the
      lethal toxin from V. basalis and hornetin from Vespa flavitarsus, respectively;
      polybitoxin-IV presented hemolytic action 20 times higher than that of PLA2 from
      A. meliferra, 17 times higher than that of neutral PLA2 from Naja nigricolis and
      about 37 times higher than that of cardiotoxin from Naja naja atra venom.

PMID- 9604294
TI  - Viper venom-induced inflammation and inhibition of free radical formation by pure
      compound (2-hydroxy-4-methoxy benzoic acid) isolated and purified from anantamul
      (Hemidesmus indicus R. BR) root extract.
AB  - The present investigation explored the possible venom neutralizing effect of a
      pure compound (2-hydroxy-4-methoxy benzoic acid) isolated and purified from the
      methanolic root extract of Hemidesmus indicus R.Rr. 2-OH-4-MeO benzoic acid
      possessed potent anti-inflammatory, antipyretic and antioxidant properties. The
      compound effectively neutralized inflammation induced by Vipera russelli venom in
      male albino mice and reduced cotton pellet-induced granuloma in rats. The
      compound produced a significant fall in body temperature in yeast-induced pyrexia
      in rats but did not change the normothermic body temperature. The compound
      effectively neutralized viper venom-induced changes in serum phosphatase and
      transaminase activity in male albino rats. It also neutralized free radical
      formation as estimated by TBAPS and superoxide dismutase activities. The
      antisnake venom activity of the pure compound is partly mediated through the
      above physiological process.

PMID- 9604295
TI  - Comparison of the immunogenicity of wasp venom peptides with or without
      carbohydrate moieties.
AB  - Three synthetic vespulakinin analogues either with or without carbohydrate
      moieties and mastoparan B isolated from Vespa basalis venom were investigated for
      their immunogenic activity and solution conformation. Mice immunized with these
      wasp venom peptides, with the exception of (Gal alpha)Thr3, (Gal alpha)Thr4
      vespulakinin 1, showed positive antibody responses. However, the response
      elicited by mastoparan B was much higher than those induced by vespulakinin
      analogues. The class of antibody induced by these peptides was identified as an
      IgG1 isotype with kappa-light chain, suggesting stimulation of a T-cell-dependent
      immune response by these peptides. According to the circular dichroism spectra of
      these peptides, the structures of the vespulakinin analogues in solution were
      largely unordered, while mastoparan B exhibited a conformation rich in alpha
      helices. The presence of carbohydrate moieties and the rather random structure in
      vespulakinins may interfere with T-cell recognition of the peptides, leading to
      lower immune responses.

PMID- 9604297
TI  - Bibliography of toxinology.

PMID- 9604296
TI  - The antinociceptive effect of Crotalus durissus terrificus snake venom is mainly
      due to a supraspinally integrated response.
AB  - The antinociceptive effect of Crotalus durissus terrificus snake venom,
      previously demonstrated in the hot-plate test, was investigated in mice using the
      tail-flick model. The venom, administered by the intraperitoneal, subcutaneous or
      oral route, did not modify the basal latency time to the noxious stimulus and the
      association of the venom with morphine did not alter the opioid analgesic effect
      of this drug. These data indicate that the antinociceptive effect of the venom is
      mainly due to a supraspinally integrated response.

PMID- 9604298
TI  - Metabolism of Zaleplon by human hepatic microsomal cytochrome P450 isoforms.
AB  - 1. The metabolism of Zaleplon (CL-284,846; ZAL) has been studied in human liver
      microsomal preparations and in cDNA-expressed human cytochrome P450 (CYP)
      isoforms. 2. Human liver microsomes catalysed the NADPH-dependent N-deethylation
      of ZAL to DZAL (CL-284,859), but not to two other known in vivo metabolites,
      namely M1 (CL-345,644) and M2 (CL-345,905). Sigmoidal kinetic plots were observed
      for ZAL deethylation indicating positive cooperativity. 3. The metabolism of ZAL
      to DZAL was determined in a characterized bank of 24 human liver microsomal
      preparations. Good correlations (r2 = 0.734-0.937) were observed with caffeine 8
      hydroxylase, diazepam 3-hydroxylase, dextromethorphan N-demethylase and
      testosterone 2 beta-, 6 beta- and 15 beta-hydroxylase activities, which are all
      catalysed by CYP3A isoforms. In contrast, poor correlations (r2 = 0.152-0.428)
      were observed for enzymatic markers for CYP1A2, CYP2A6, CYP2C9/10, CYP2D6, CYP2E1
      and CYP4A9/11. 4. The metabolism of ZAL to DZAL in human liver microsomes was
      inhibited to 6-15% of control by 5-50 microM of the mechanism-based CYP3A
      inhibitor troleandomycin. Whereas some inhibition of DZAL formation was observed
      in the presence of 200 microM diethyldithiocarbamate, 5-50 microM furafylline, 2
      20 microM sulphaphenazole, 50-500 microM S-mephenytoin and 1-10 microM quinidine
      had little effect. 5. Using human B-lymphoblastoid cell microsomes containing
      cDNA-expressed CYP isoforms, ZAL was metabolized to DZAL by CYP3A4, hut not to
      any great extent by CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and
      CYP2E1. 6. In contrast with ZAL, the NADPH-dependent N-deethylation of M2 to M1
      proceeded at only a very low rate with both human liver microsomes and cDNA
      expressed CYP3A4. 7. In summary, by correlation analysis, chemical inhibition
      studies and the use of cDNA-expressed CYPs, ZAL N-deethylation to DZAL in human
      liver appears to be catalysed by CYP3A isoforms.

PMID- 9604299
TI  - Effect of cold and warm ischaemia on drug metabolism in isolated hepatocytes and
      slices from human and monkey liver.
AB  - 1. The influence of short-term cold storage in University of Wisconsin organ
      preservation solution (UW) on the ability to metabolize lidocaine, testosterone
      and 7-ethoxycoumarin in isolated human and cynomolgus monkey (Macaca
      fascicularis) hepatocytes and liver slices has been investigated. 2. The human
      liver tissue was obtained from two different sources, i.e. healthy liver tissue
      from patients undergoing partial hepatectomy because of metastases of colorectal
      carcinoma (PH livers) and donor tissue remaining as surgical waste after reduced
      size or split liver transplantation (Tx livers). Tx livers were perfused in situ
      with ice-cold UW avoiding warm ischaemia. This in contrast with PH livers, where
      the operation caused warm ischaemia for 5-90 min. 3. Liver slices and hepatocytes
      from cynomolgus monkey liver showed comparable metabolic rates for the substrates
      tested, indicating that all hepatocytes in the slice are participating in the
      biotransformation of the substrates. These monkey liver preparations can be
      stored up to 18 h with only a slight loss of their metabolic capacity. 4. Liver
      slices and isolated hepatocytes from the Tx livers as well as isolated cells from
      the PH livers could also be stored up to 18 h without losing metabolic capacity.
      However, for liver slices prepared from PH livers cold storage is not
      recommended, because metabolic function was reduced by approximately 40% after 18
      h.

PMID- 9604300
TI  - Use of precision-cut rat liver slices for studies of xenobiotic metabolism and
      toxicity: comparison of the Krumdieck and Brendel tissue slicers.
AB  - 1. In this study we have compared freshly cut and cultured precision-cut rat
      liver slices produced by the Krumdieck and Brendel-Vitron tissue slicers. 2. No
      significant differences were observed in levels of protein, potassium, total
      glutathione (i.e. GSH and GSSG), reduced glutathione (GSH) and cytochrome P450
      and activities of 7-ethoxyresorufin O-deethylase and 7-benzoxyresorufin O
      debenzylase in freshly cut rat liver slices produced by the two tissue slicers.
      However, levels of oxidized glutathione (GSSG) were significantly greater in
      liver slices produced with the Brendel-Vitron tissue slicer. 3. Precision-cut rat
      liver slices produced with both tissue slicers were cultured for 0 (i.e. a 1-h
      preincubation), 24 and 72 h in a dynamic organ culture system in an atmosphere of
      either 95% 02/5% CO2 or 95% air/5% CO2. 4. Apart from small differences in
      glutathione levels in 0 and 24 h cultured liver slices, no significant
      differences were observed in the parameters measured between liver slices
      prepared with both tissue slicers and cultured in both gas phases. 5. With liver
      slices produced by both tissue slicers 50 microM sodium arsenite produced a
      greater induction of heat shock protein 70 levels in slices cultured for 24 h in
      a high oxygen than in an air atmosphere. 6. These results suggest that both
      tissue slicers can readily produce precision-cut liver slices for studies of
      xenobiotic metabolism and toxicity. However, the data suggest that for any given
      application of precision-cut tissue slices it is desirable to establish optimal
      culture conditions

PMID- 9604301
TI  - 19F-NMR and directly coupled HPLC-NMR-MS investigations into the metabolism of 2
      bromo-4-trifluoromethylaniline in rat: a urinary excretion balance study without
      the use of radiolabelling.
AB  - 1. The metabolic fate and urinary excretion of 2-bromo-4-trifluoromethylaniline
      has been studied in rat using 19F-NMR spectroscopic and directly coupled HPLC-NMR
      MS methods. The compound was dosed to Sprague-Dawley rats (50 mg kg-1, i.p.) and
      urine collected over 0-8, 8-24 and 24-48 h post-dosing. 2. A total urinary
      recovery of 53.5 +/- 7.0% of the dose was achieved up to 48 h after dosing. The
      major metabolite in the urine was identified as 2-amino-3-bromo-5
      trifluoromethylphenylsulphate accounting for a total of 35.7 +/- 6.2% of the
      dose. 3. Further metabolites detected were 2-bromo-4
      trifluoromethylphenylhydroxylamine-1V-glucuronide (9.7 +/- 0.2% of the dose), 2
      bromo-4-trifluoromethylaniline-N-glucuronide (3.0 +/- 0.3%) and 2-amino-3-bromo-5
      trifluoromethylphenylglucuronide (2-St 0-4). Minor metabolites, including 2-bromo
      4-trifluoromethylphenylhydroxylamine-O-glucuronide, 2-amino-3-bromo-5
      trifluoromethylphenol and 2-bromo-4-trifluoromethylphenylsulphamate, in total
      accounted for 2.3 +/- 0.9% of the dose. 4. Directly coupled HPLC-NMR-MS and 19F
      NMR spectroscopy proved to be efficient techniques for the unequivocal and rapid
      determination of the urinary metabolic fate and excretion balance of fluorinated
      xenobiotics without the need for radiolabelling.

PMID- 9604302
TI  - In vitro biotransformation of flavonoids by rat liver microsomes.
AB  - 1. Sixteen naturally occurring flavonoids were investigated as substrates for
      cytochrome P450 in uninduced and Aroclor 1254-induced rat liver microsomes.
      Naringenin, hesperetin, chrysin, apigenin, tangeretin, kaempferol, galangin and
      tamarixetin were all metabolized extensively by induced rat liver microsomes but
      only to a minor extent by uninduced microsomes. No metabolites were detected from
      eriodictyol, taxifolin, luteolin, quercetin, myricetin, fisetin, morin or
      isorhamnetin. 2. The identity of the metabolites was elucidated using lc-ms and
      1H-nmr, and was consistent with a general metabolic pathway leading to the
      corresponding 3',4'-dihydroxylated flavonoids either by hydroxylation or
      demethylation. Structural requirements for microsomal hydroxylation appeared to
      be a single or no hydroxy group on the B-ring of the flavan nucleus. The presence
      of two or more hydroxy groups on the B-ring seemed to prevent further
      hydroxylation. The results indicate that demethylation only occurs in the B-ring
      when the methoxy group is positioned at C4', and not at the C3'-position. 3. The
      CYP1A isozymes were found to be the main enzymes involved in flavonoid
      hydroxylation, whereas other cytochrome P450 isozymes seem to be involved in
      flavonoid demethylation.

PMID- 9604303
TI  - Linkage between the distribution of mutations in the CYP2C18 and CYP2C19 genes in
      the Japanese and Caucasian.
AB  - 1. Two different types of genetic polymorphisms in each of CYP2C18 and CYP2C19
      genes were examined and compared with respect to their frequencies in
      distribution in liver DNA of 39 Japanese and 45 Caucasians. 2. Individuals who
      were classified into CYP2C19m1 (as detected with SmaI digestion) in exon 5 of
      CYP2C19 gene were found to display a CYP2C18m1 polymorphism (as detected with
      DdeI digestion) in the 5'-flanking region of CYP2C18 gene in Japanese and
      Caucasian populations. The Japanese subjects who were classified into CYP2C19m2
      (as detected with BamHI digestion) in exon 4 of CYP2C19 gene were found to have a
      CYP2C18m2 genetic polymorphism (as detected with Tsp509I digestion) in exon 2 of
      CYP2C18 gene. None of the Caucasians had the CYP2C18m2 nor CYP2C19m2 alleles. 3.
      Frequencies in two types (C416T in exon 3, A1061C in exon 7) of CYP2C9 genetic
      polymorphism were found to be independent to those of CYP2C18 and CYP2C19 genetic
      polymorphisms in these samples. 4. Thus, the results suggest that the CYP2C18
      gene is localized very closely to the CYP2C19 gene on the same human chromosome.

PMID- 9604304
TI  - Disposition kinetics of cobalt mesoporphyrin in mouse, rat, monkey and dog.
AB  - 1. Radiometric and UV analyses indicated > 95% unchanged cobalt mesoporphyrin
      (CoMP) in plasma after i.v. or i.m. administration. Blood clearance of CoMP is <
      2% of hepatic blood flow in mouse and rat, and < 0.5% of hepatic blood flow in
      monkey and dog. CoMP elimination t1/2 ranged from 3.1 to 9.9 days in animals
      after i.v. administration. 2. CoMP is highly (> 99.5%) bound to plasma proteins,
      but has low affinity for blood cells (Kp < 0.15). The volume of CoMP distribution
      (Vss < 0.91/kg) is reflective of a distribution to total body water following
      i.v. administration to mouse, rat, monkey and dog. 3. [14C]CoMP reached highest
      levels in rat tissue between 1 and 4 days following i.m. injection. Liver, kidney
      cortex, lymph node, adrenal and spleen demonstrated greatest uptake of
      radiolabel. Concentration in tissues was readily detectable at 60 days post-dose.
      4. CoMP was slowly absorbed after i.m. administration showing dose-dependent
      pharmacokinetics. The major route of radiolabel elimination was faecal excretion
      (54% of dose) in rat after an i.m. dose of [14C]CoMP. Approximately 1% of the 14C
      dose was recovered in the urine over 7 days post-dose. 5. As a polar
      metalloporphyrin, CoMP has low clearance, restricted tissue distribution and long
      elimination t1/2 in the laboratory animals.

PMID- 9604305
TI  - Symbolic addition in protein electron crystallography--a method for finding
      projected helices.
AB  - The crystal structure of orthorhombic bacteriorhodopsin was determined in
      projection by direct methods from electron diffraction amplitudes, assuming that,
      after re-scaling the problem, the Fourier transform of projected alpha-helices
      could be modeled by atomic scattering factors. A basic set comprising two origin
      defining phases, two phase values from sigma 1 triple estimates and an algebraic
      unknown (resolved early in the phase determination) was extended to a total set
      of 20 terms, with only two errors. Five helix sites were observed in the first
      potential map and, after three cycles of Fourier refinement, the rest of the
      asymmetric unit was found. The overall phase accuracy was 47 degrees or 22
      degrees for the 25 most intense reflections.

PMID- 9604306
TI  - Bis(acetylacetonato-O,O')(eta 4-trans-2,4-hexadiene)ruthenium(II) 1/6-ethanol
      solvate.
AB  - The title compound, [Ru(C5H7O2)2(C6H10)].1/6C2H6O, has a pseudo-octahedrally
      coordinated RuII center, where two coordination sites are occupied by a diene
      ligand. The diene ligand exhibits a eta 4-trans-diene coordination mode. The
      compound crystallizes in space group R3, incorporating disordered ethanol in
      cylindrical voids.

PMID- 9604307
TI  - 4-Nitro-1-(trimethylsilylethynyl)benzene.
AB  - The title molecule, C11H13NO2Si, lies on a mirror plane, with only one methyl
      group lying out of plane. The C[symbol: see text]C triple bond has a length of
      1.199 (4) A. Bond angles Si-C[symbol: see text]C and C[symbol: see text]C-C(Ar)
      are 177.9 (3) and 178.0 (3) degrees, respectively. The Si-Csp3 bond lengths are
      1.831 (4) and 1.838 (3) A, while the Si-Csp distance is 1.839 (3) A.

PMID- 9604308
TI  - Mephentermine hemisulfate monohydrate: an adrenergic agent.
AB  - The title molecule, a hydrated hemisulfate salt of ethyl(2-methyl-1-phenyl-2
      propyl)ammonium, C11H18N+.0.5SO4(2-).H2O, consists of a phenethylamine skeleton
      in which the N atom is protonated. There are two molecules in the asymmetric
      unit, with the S atom of the SO4(2-) ion lying on a pseudo-twofold axis. The
      ethylamine side chain is in an extended conformation in both the symmetry
      independent molecules. The distance of the N atom from the centre of the benzene
      ring is 5.1 A for molecule 1 and 5.3 A for molecule 2. The packing is stabilized
      by N-H...O and O-H...O hydrogen bonds.

PMID- 9604309
TI  - Thiophene-2-carbaldehyde N-(2,4-dinitrophenyl)-N-methylhydrazone.
AB  - Molecules of the title compound, C12H10N4O4S, are linked through intermolecular
      hydrogen bonds to form a dimeric structure. The crystal structure of the dimer is
      stabilized by two intermolecular hydrogen bonds of the C-H...O type. The C...O
      intermolecular contact distance is 3.339(3) A, and the C=N and N-N distances are
      1.279(2) and 1.371(7) A, respectively. One O atom of the 2-nitro group is
      disordered over two sites.

PMID- 9604310
TI  - Phenolphthalein and 3',3"-dinitrophenolphthalein.
AB  - Phenolphthalein, C20H14O4, crystallized in the noncentrosymmetric space group
      Pna2(1) with two crystallographically inequivalent molecules. Each of these is
      linked to four others of its own type by four hydrogen bonds having
      Odonor...Oacceptor distances ranging from 2.631 (4) to 2.787 (4) A. While chains
      of hydrogen bonds propagate in a number of directions in this structure, cyclic
      hydrogen bonding is not observed. 3',3"-Dinitrophenolphthalein, C20H12N2O8,
      crystallized in the centrosymmetric space group Pbcn with a single molecule in
      the asymmetric unit. Each molecule is linked to three others by four hydrogen
      bonds having Odonor...Oacceptor distances ranging from 2.572 (4) to 3.274 (3) A.
      Although chains of hydrogen bonds are prominent in this structure, cyclic
      hydrogen bonding also occurs and forms dimers. As expected on the basis of the
      excess of potential acceptor O atoms over donors in both structures, significant
      C-H...O interactions are also abundant.

PMID- 9604311
TI  - Concepts in imaging and microscopy: color image processing for microscopy.
AB  - Digital image analysis has long been applied to monochrome images from the light
      microscope. Using these techniques one can locate, measure, identify, and count
      the objects of interest in a microscope field of view. Since microscope images
      often contain color information of interest, it is now becoming more common to
      analyze the spectral content of images as well. Although most of the digital
      imaging techniques developed for monochrome microscopy work well with color
      images, there are a few considerations specific to the analysis of multispectral
      imagery. These include obtaining a properly balanced multicolor digital image,
      specifying the color components of the image, and compensating for imperfect
      separation among the color channels.

PMID- 9604312
TI  - Vestimentiferan on a whale fall.
AB  - Discovery of chemosynthetic communities associated with whale bones led to the
      hypothesis that whale falls may serve as stepping-stones for faunal dispersal
      between disjunct hydrothermal vents and cold seeps on the ocean floor (1). The
      initial observation was followed by a faunal inventory that revealed a diverse
      assemblage of microbes and invertebrates, supported by chemoautotrophic
      production, living in close proximity to whale remains (2, 3). To date, the
      conspicuous absence from whale falls of vestimentiferan tubeworms (a predominant
      constituent of eastern Pacific vent and seep habitats) has been a major objection
      to the stepping-stone hypothesis (4-5). We report the first evidence of a
      vestimentiferan tubeworm associated with a whale fall (Fig. 1). The tubeworm,
      Escarpia spicata, was identified by morphological criteria and DNA sequence data
      from a portion of the mitochondrial cytochrome oxidase C subunit I (COI) gene.
      Additionally, the bacterial endosymbiont in the tubeworm possessed a 16S rRNA
      gene that was similar to that of endosymbionts from vestimentiferans in
      sedimented cold-seep environments.

PMID- 9604313
TI  - Characterization of Aplysia attractin, the first water-borne peptide pheromone in
      invertebrates.
AB  - Although animals in the genus Aplysia are solitary during most of the year, they
      form breeding aggregations during the reproductive season. The aggregations
      contain both mating and egg-laying animals and are associated with masses of egg
      cordons. The egg cordons are a source of pheromones that establish and maintain
      the aggregation, but none of the pheromonal factors have been chemically
      characterized. In these studies, specimens of Aplysia were induced to lay eggs,
      the egg cordons collected and eluted, and the eluates fractionated by C18
      reversed-phase HPLC. Four peak fractions were bioassayed in a T-maze. All four
      increased the number of animals attracted to a nonlaying conspecific and were
      thus subjected to compositional and microsequence analysis. Each contained the
      same NH2-terminal peptide sequence. The full-length peptide ("attractin") was
      isolated from the albumen gland, a large exocrine organ that packages the eggs
      into a cordon. The complete 58-residue sequence was obtained, and it matched that
      predicted by an albumen gland cDNA. Mass spectrometry showed that attractin is 21
      wt.% carbohydrate as the result of N-linked glycosylation. T-maze bioassays
      confirmed that the full-length peptide is attractive. Attractin is the first
      water-borne peptide pheromone characterized in molluscs, and the first in
      invertebrates.

PMID- 9604314
TI  - A major protein precursor of zebra mussel (Dreissena polymorpha) byssus: deduced
      sequence and significance.
AB  - The zebra mussel is a nonindigenous invader of North American lakes and rivers
      and one of the few freshwater bivalve molluscs having a byssus--a sclerotized
      organ used by the mussel for opportunistic attachment to hard surfaces. We have
      sequenced a foot-specific cDNA whose composite protein sequence was deduced from
      a series of overlapping but occasionally nonidentical cDNA fragments. The overall
      deduced sequence matches tryptic peptides from a major byssal precursor protein-
      Dreissena polymorpha foot protein 1 (Dpfp1). The calculated mass of Dpfp1 is 49
      kDa; but this is known to be extensively hydroxylated and O-glycosylated during
      maturation. Purified native Dpfp1 analyzed using matrix-assisted laser-desorption
      ionization mass spectrometry with time-of-flight indicates that the protein
      occurs as at least two size variants with masses of 48.6 and 54.5 kDa. In all
      probability, the sequence variants reported in this study are related to the
      larger mass variant. Dpfp1 has a block copolymer-like structure defined by two
      consensus motifs that are sharply segregated into domains. The N-terminal side of
      Dpfp1 has 22 tandem repeats of a heptapeptide consensus (P-[V/E]-Y-P-[T/S/delta]
      [K/Q]-X); the C-terminal side has 16 repeats of a tridecapeptide motif (K-P-G-P-Y
      D-Y-D-G-P-Y-D-K). Both consensus repeats are unique, with some limited homology
      to other proteins functioning in tension: marine mussel adhesives, plant
      extensins, titin, and trematode eggshell precursors.

PMID- 9604315
TI  - Synthesis and anti-trypanosomal activity of novel 5-nitro-2-furaldehyde and 5
      nitrothiophene-2-carboxaldehyde semicarbazone derivatives.
AB  - Several novel semicarbazones derivatives were prepared from 5-nitro-2-furaldehyde
      or 5-nitrothiophene-2-carboxaldehyde, and tested in vitro as potential anti
      trypanosomal agents. The compounds were prepared in good to excellent yields in 2
      3 steps from readily available starting materials. Some derivatives were found to
      be active against Trypanosoma cruzi with an activity similar to that of
      Nifurtimox.

PMID- 9604316
TI  - Prodrugs. Part 3. 2-Formylphenyl esters of indomethacin, ketoprofen and ibuprofen
      and 6-substituted 2-formyl and 2-acylphenyl esters of aspirin.
AB  - The synthesis and study of a novel series of potential prodrugs of indomethacin,
      ketoprofen, ibuprofen and aspirin are reported. 2-Formylphenyl esters of the
      NSAIDs, together with two 6-substituted 2-formyl and two 2-acylphenyl aspirins
      and 4-formylphenyl indomethacin, have been prepared. A study of their alkaline
      and neutral hydrolysis shows that these compounds, with the exception of 2
      acetylphenyl aspirin, act as true prodrugs of the NSAIDs, giving the NSAID and
      acylphenol. The rates of hydrolysis and activation parameters indicate that the 2
      acylphenyl esters employ an intramolecular catalytic route. The 2-formylphenyl
      esters were more potent as anti-inflammatory agents than the parent compounds in
      the carragheenan-induced paw oedema test.

PMID- 9604317
TI  - Synthesis and preliminary pharmacological investigation of some 2-[4
      (dialkylaminoalkoxy)phenyl]benzotriazoles and their N-oxides.
AB  - A set of 2-[4-(dialkylaminoalkoxy)phenyl]benzotriazoles and corresponding N
      oxides was prepared. In a preliminary pharmacological investigation concerning
      some of these compounds, several in vitro and in vivo activities were shown. At
      concentrations in the range of 3-10 microM all tested compounds strongly
      inhibited (50-100%) the guinea pig ileum contractions induced either electrically
      or by means of several agonists; of particular interest was the antagonism to
      leukotriene D4. Compound 5b inhibited platelet aggregation induced by thromboxane
      A2, PAF and ADF (but not by arachidonic acid) and increased the bleeding time in
      mice. Compounds 5b and 6b protected mice from potassium cyanide hypoxia and
      exerted anti-hypercholesterolemic action; the first compound produced a ratio
      between HPL and total serum cholesterol concentrations below 0.92, thus
      indicating a potential anti-atherogenic activity.

PMID- 9604318
TI  - Synthesis and anti-microbial activity of some imidazo[1',2':5,6]pyrimido[4,5
      c]pyridazines and related heterocycles.
AB  - The synthesis of the title heterocycles was achieved using 3-amino-5,6
      diphenylpyridazine-4-carbonitrile (4) as a starting material. This compound was
      converted into the corresponding 4-imidazolinyl derivative 5 which was then
      subjected to cyclization reactions to afford the title compounds.

PMID- 9604319
TI  - 2-Mercapto-propylamine: radiopharmacology in mice, pharmacokinetic studies in
      mice and in rats, mutagenicity and differential distribution between tissues and
      EMT6 tumour in mice.
AB  - Radiopharmacological studies conducted with 2-mercapto-propylamine (2MPA), a
      methylated derivative of cysteamine, indicated a good efficiency in whole body
      irradiated mice as observed over a period of 9 months. Its efficacy was also
      checked for supralethal irradiations of restricted body parts: in the brain and
      the rectum. The diffusion of 14C-labelled 2MPA was assessed by an
      autoradiographic study and measurement of its distribution in the main organs in
      mice. 2MPA penetrated the blood brain barrier but concentrated preferentially in
      the liver, kidney and skin. Fixation on plasmatic proteins was much lower in rats
      than in mice but urinary and faecal eliminations were of the same order for the
      two species. An important biliary excretion of 2MPA or its metabolites in rats
      combined with their lack in the faeces underlies an entero-hepatic cycle. A
      differential diffusion of 2MPA between normal tissues in mice and EMT6 tumours
      was clearly revealed by autoradiographic observations. The ability of 2MPA to
      trap 2,2'-diphenyl 1-picryl hydrazyl, an organic free radical, was checked by in
      vitro studies. Its performance indicated that 2MPA acted at least as a free
      radical scavenger. Ames test demonstrated that 2MPA whatever the dose employed
      was not a mutagenic agent. Pharmacological and pharmacokinetical observations
      provided a better understanding of the activity of this drug.

PMID- 9604320
TI  - Characterization and applications of human epidermis reconstructed in vitro on de
      epidermized derma.
AB  - In recent years in vitro models have been developed to avoid the use of animals
      in cutaneous toxicological studies. Submerged human keratinocyte cultures in
      vitro could be so far employed as an alternative to animal testing and a good
      correlation between skin irritation and cytotoxicity has been demonstrated.
      Nevertheless, these submerged cultures are lacking in the stratum corneum which
      acts as a barrier to chemical toxicity, so that this type of culture is far from
      the in vivo situation. A better alternative method seems to be the use of in
      vitro reconstructed skin at the air-liquid interface that closely resembles the
      in vivo situation. In this work, in a first step we have characterized human
      epidermis reconstructed in vitro on de-epidermized derma (DED) after a two-week
      air exposure. Human skin reconstituted in vitro on DED was histologically similar
      to the in vivo skin. A stratified epidermis including the stratum corneum was
      obtained. The presence of basal lamina as well as of various important markers
      for epidermal differentiation (involucrin, K10 keratin, and filaggrin) were
      revealed. In a second step we have tested the cytotoxic and morphological effects
      of four surfactants on our model. A good rank correlation has been shown to exist
      between the irritation potency of surfactants on our model and reported ocular
      irritancy in vivo. From our results, in vitro reconstituted human skin could
      represent an attractive model for irritancy testing and could be an in vitro
      replacement for animal testing.

PMID- 9604321
TI  - Quinoxaline chemistry. Part 9. Quinoxaline analogues of trimetrexate (TMQ) and 10
      propargyl-5,8-dideazafolic acid (CB 3717) and its precursors. Synthesis and
      evaluation of in vitro anticancer activity.
AB  - Eighteen quinoxalines bearing a methyleneanilino or
      methyleneaminobenzoylglutamate group on position 6 of the ring and various
      lipophilic substituents on positions 2 and 3 were prepared in order to discover
      if their structural analogy with both trimetrexate (TMQ) and 10-propargyl-5,8
      dideazafolic acid (CB 3717) might display in vitro anticancer activity. Among
      these, 12 compounds were selected at the National Cancer Institute, Bethesda, MD,
      USA; they exhibited moderate (4b,d,i,l,m and 8) to strong (4f,h and 5a,e) cell
      growth inhibition at a concentration of 10(-4) M. Interesting selectivities were
      also recorded between 10(-8) and 10(-6) M. These analogues proved to be less
      potent inhibitors of tumor cells than other classical and non-classical
      antifolate analogues previously described by us.

PMID- 9604322
TI  - Quinoxaline chemistry. Part 10. Quinoxaline 10-oxa-analogues of trimetrexate
      (TMQ) and of 5,8-dideazafolic acid. Synthesis and evaluation of in vitro
      anticancer activity.
AB  - Among twenty-eight novel compounds (twenty-two 2,3-disubstituted-6-[(substituted
      phenoxy)methyl-quinoxalines and six 4-[(2,3-disubstituted-quinoxalin-6
      yl)methoxy]benzoylglutamates ) only thirteen were selected at NCI for evaluation
      of their in vitro anticancer activity. The results have shown that compounds
      3l,c,b,e and 4b were endowed with significantly high values of percent tumor
      growth inhibition on several tumor cell lines at 10(-4) M, while compound 3t was
      characterized by a high selectivity, being still strongly inhibiting on three
      cell lines at 10(-5) M. Comparison of the presently observed activity with that
      of the previously described aza-analogues confirms that the effected isosteric
      substitution is highly valuable in some cases.

PMID- 9604323
TI  - Synthesis and in vitro anticancer activity evaluation of biscarbamic esters of
      2,3-bis(hydroxymethyl)-1-methyl-7- and 7,8-substituted-benzo[g]indoles.
AB  - A series of various bis(hydroxymethyl) carbamate derivatives of 7-mono- and 7,8
      disubstituted-1-methyl-benzo[g]indoles was prepared in order to evaluate their
      cytostatic and cytotoxic activities in vitro. Compounds 2a-h showed significant
      tumor growth inhibition activity and were more potent than the 4,5
      dihydrobenzo[g]indole analogues previously described. Compound 2a was the most
      active in this series, showing high activity and selectivity for some human
      cancer cell lines in the National Cancer Institute screen.

PMID- 9604324
TI  - Synthesis of N-(4-aryl-1-piperazinylbutyl)-substituted 7,8-benzo-1,3
      diazaspiro[4,5]decane-2,4-dione derivatives with potential anxiolytic activity.
AB  - Continuing our studies connected with the design of new anxiolytics we have now
      synthesized a series of new compounds, derivatives of 7,8-benzo-1,3
      diazaspiro[4,5]decane-2,4-dione bearing a 4-aryl-1-piperazinylbutyl group
      attached to the imide nitrogen. One single compound was submitted to the 5-HT1A
      receptor binding assay and found to display the expected--though rather weak-
      receptorial affinity.

PMID- 9604325
TI  - Simultaneous variation of temperature and gradient steepness for reversed-phase
      high-performance liquid chromatography method development. I. Application to 14
      different samples using computer simulation.
AB  - The optimized reversed-phase HPLC separation of 14 different samples is reported,
      based on simultaneous changes in temperature and gradient steepness. Four
      experimental runs are required for each sample, following which preferred
      conditions can be predicted using computer simulation software (DryLab). The
      overall accuracy and effectiveness of this method development approach is
      discussed, with particular attention to the use of resolution maps provided by
      the software. These maps are useful for maximizing resolution for the total
      sample, for optimizing the separation of a smaller number of selected sample
      compounds, and as an initial step in the separation of more demanding samples.

PMID- 9604326
TI  - Simultaneous variation of temperature and gradient steepness for reversed-phase
      high-performance liquid chromatography method development. II. The use of further
      changes in conditions.
AB  - The preceding paper (Part I) suggests that simply optimizing temperature and
      gradient steepness will often provide an adequate reversed-phase HPLC separation.
      In some cases, however, this procedure will prove unsuccessful, and then further
      method-development experiments (involving change in other separation conditions)
      will be required. One strategy is to change a variable other than temperature or
      gradient steepness, followed by re-optimization of the latter two variables. The
      present paper examines the application of this approach with the aid of computer
      simulation to several samples.

PMID- 9604327
TI  - Use of compact, porous units with immobilized ligands with high molecular masses
      in affinity chromatography and enzymatic conversion of substrates with high and
      low molecular masses.
AB  - Different ligands with high molecular masses are immobilized on compact, porous
      separation units and used for affinity chromatography. In subsequent experiments
      different enzymes are immobilized and used for converting substrates with low and
      high molecular masses. Disk or tube with immobilized concanavalin A (ConA) are
      used as model systems for lectin affinity chromatography. The enzyme glucose
      oxidase is used as a standard protein to test the ConA units. Subsequently
      glycoproteins from plasma membranes of rat liver are separated, using units with
      immobilized ConA. The enzyme dipeptidyl peptidase i.v., which is used as a model
      protein in the experiments, is enriched about 40-fold in a single step, with a
      yield of over 90%. The results are only slightly better than those obtained with
      ConA when it is immobilized on bulk supports. The important improvement lies in
      the reduction of separation time to only 1 h. Experiments concerning the
      isolation of monoclonal antibodies against clotting factor VIII (FVIII) are
      carried out on disks, combining anion-exchange chromatography and protein A
      affinity chromatography as a model for multidimensional chromatography. Both IgG
      (bound to the protein A disk) and accompanying proteins (bound to the anion
      exchange disk) from mouse ascites fluid are retarded and eluted separately. With
      the immobilized enzymes invertase and glucose oxidase (GOX) the corresponding
      substrates with low molecular masses, saccharose and glucose, are converted. It
      is shown that the amount of immobilized enzyme and the concentration of the
      substrate are responsible for the extent of the conversion, whereas the flow
      rates used in the experiments have no effect at all. The influence of
      immobilization chemistry was investigated with GOX. Indirect immobilization with
      ConA as spacer proved to be the best alternative. With trypsin, immobilized on a
      disk, substrates with high molecular masses are digested in flow-through. For
      optimal digestion the proteins have to be denatured in the buffer for sodium
      dodecyl sulfate-polyacrlyamide gel electrophoresis prior to application. In
      contrast to the conversion of substrates with low molecular masses, flow-rates
      play an important part in conversion of substrates with high molecular masses.
      With lower flow-rates a higher degree of digestion is achieved.

PMID- 9604328
TI  - Salt-promoted adsorption of proteins onto amphiphilic agarose-based adsorbents.
      II. Effects of salt and salt concentration.
AB  - The effects of different types of salts and salt concentrations on the
      selectivity in the adsorption of serum proteins have been compared for the
      amphiphilic agarose-based adsorbents Phenyl-Sepharose, Octyl-Sepharose, butyl
      agarose and mercaptopyridine-derivatized agarose. By use of multivariate
      analysis, the complex interrelationships for the different combined effects were
      evaluated. From these analyses conclusions about similarities and/or
      dissimilarities in the mechanisms involved in adsorption of proteins on
      respective adsorbent were made.

PMID- 9604329
TI  - Transcription factor-green fluorescent protein chimeric fusion proteins and their
      use in studies of DNA affinity chromatography.
AB  - A new plasmid, pJ22, was produced by introducing the enhanced green fluorescent
      protein (GFP) coding sequence into the pET28 plasmid while retaining much of the
      multiple cloning site. This new plasmid was then used to produce a chimeric
      fusion protein containing the DNA-binding region of the rat liver CAAT enhancer
      binding protein (C/EBP) fused to the COOH-terminus of GFP. This new GFP-C/EBP
      fusion protein also contains (His)6 to facilitate purification by Ni(2+)-agarose
      and several other useful features. The plasmid and protein were developed to
      allow us to more rapidly investigate the DNA-Sepharose affinity chromatography of
      transcription factors. The GFP-C/EBP protein is virtually identical in its DNA
      binding properties to a well-characterized, bacterially expressed protein called
      C/EBP 62 which has been shown to mimic rat wild-type C/EBP DNA-binding. GFP-C/EBP
      also binds to DNA-Sepharose which contains the CAAT element and is eluted by a
      salt gradient. Salt-dependent elution was highly temperature-dependent over the
      range of 4-19 degrees C. Since temperature-dependent DNA-binding has also been
      reported for other DNA-binding proteins, this may also occur with other
      transcription factors. DNA-affinity chromatography gave higher purity than that
      obtained by Ni(2+)-agarose chromatography and chromatography on the same DNA
      Sepharose column at two different temperatures resulted in the greatest
      purification, to near homogeneity. This temperature-dependent affinity
      chromatography provides an important new approach to transcription factor
      purification.

PMID- 9604330
TI  - New chemically modified polymeric resin for solid-phase extraction of pesticides
      and phenolic compounds from water.
AB  - A new chemically modified polymeric resin, with an o-carboxybenzoyl moiety, is
      developed to be used in the on-line solid-phase extraction (SPE) of some
      pesticides and phenolic compounds from aqueous samples, in order to obtain better
      breakthrough volumes than other commercial sorbents. The chemical introduction of
      this moiety improves the efficiency of SPE by providing better surface contact
      with aqueous samples. This synthesized sorbent enables higher volumes of sample
      to be concentrated for determining polar compounds. When analyzing real samples,
      tap and river waters, different quantities of sulphite were added to decrease the
      initial band due to fulvic and humic acids. The matrix peaks decreased and there
      were no losses in the studied compounds observed when 500 and 1000 microliters of
      10% Na2SO3 solution for every 100 ml of sample were added to tap and river water,
      respectively.

PMID- 9604331
TI  - Determination of acidic herbicides using liquid chromatography with pneumatically
      assisted electrospray ionization mass spectrometric and tandem mass spectrometric
      detection.
AB  - Liquid chromatography-pneumatically assisted electrospray mass spectrometry with
      negative ionization has been used for the determination of acidic herbicides in
      ground water. Eighteen pesticides or pesticide degradation products belonging to
      several different groups of acidic herbicides (phenoxy acids, sulfonylureas,
      phenols, etc.) were covered in the study. Optimization of electrospray inlet
      conditions is described as well as results from investigations of the linearity
      of the detector response. Conditions for tandem mass spectrometry (MS-MS)
      detection of characteristic daughter ions formed by collision-induced
      dissociation (CID) of the parent ion are described and a comparison of obtainable
      instrument detection limits by single MS and MS-MS was made. Detection limits
      using MS in the selected ion monitoring (SIM) mode were generally in the order of
      1 microgram/l or below, whereas detection limits were three-four times higher
      using MS-MS detection. A principle of analysis is proposed based on single
      quadrupole MS as a method for quantitative determination followed by verification
      of positive findings by CID MS-MS. Application of the method for detecting acidic
      herbicides residues in a "real-world" ground water sample is demonstrated.

PMID- 9604332
TI  - Determination of chlorobenzenes in water by solid-phase extraction and gas
      chromatography-mass spectrometry.
AB  - A method is described which permits the trace analysis of 10 chlorobenzenes in
      aqueous samples. Chlorobenzenes were extracted from water samples by solid-phase
      extraction with a C18 cartridge and analysis was carried out by gas
      chromatography-mass spectrometry in the selected-ion monitoring mode. The
      recovery and precision of the method were evaluated by extraction of spiked
      reagent-grade water at concentration levels of 0.1, 1.0 and 10.0 micrograms/l.
      This method was applied to the determination of chlorobenzenes in tap, ground and
      river water. By preparing 200 ml of environmental water samples, the detection
      limits of the compounds studied were in the range of 0.010-0.042 microgram/l.

PMID- 9604333
TI  - Analysis of nonpolar heterocyclic amines in cooked foods and meat extracts using
      gas chromatography-mass spectrometry.
AB  - Heat processing of muscle foods gives rise to the formation of mutagenic and
      carcinogenic heterocyclic amines, often at ng/g levels. A gas chromatographic
      mass spectrometric (GC-MS) technique was introduced for the analysis of nonpolar
      heterocyclic amines in common cooked meats, pan residues, and meat extracts after
      solid-phase extraction. The mutagenic heterocyclic amines 3-amino-1,4-dimethyl-5H
      pyrido[4,3-b]indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2),
      2-amino-9H-pyrido[2,3-b]indole (A alpha C) and 2-amino-3-methyl-9H-pyrido[2,3
      b]indole (MeA alpha C) were identified in several samples in amounts up to 8
      ng/g. Also the comutagenic substances 1-methyl-9H-pyrido [3,4-b]indole (harman)
      and 9H-pyrido[3,4-b]indole (norharman) were detected in the samples in amounts up
      to almost 200 ng/g. The GC-MS method can be applied without derivatisation of the
      sample. The technique offers high chromatographic efficiency, yielding detection
      limits for pure references in the range 0.1-2 ng per injection.

PMID- 9604334
TI  - Separation of polycyclic aromatic hydrocarbon metabolites by gamma-cyclodextrin
      modified micellar electrokinetic chromatography with laser-induced fluorescence
      detection.
AB  - Using a modified micellar buffer consisting of gamma-cyclodextrin (gamma-CD) and
      sodium dodecyl sulfate (SDS), we have obtained separations of hydroxy-polycyclic
      aromatic hydrocarbons (hydroxyPAHs). These compounds are oxidative products of
      mammalian PAH metabolism. The analytes were detected with a commercial laser
      induced fluorescence (LIF) detector. A number of hydroxyPAH isomers could be
      separated by changes in gamma-CD concentration. Baseline resolution of 12
      hydroxyPAHs was obtained using 30 mM borate, 60 mM SDS and 40 mM gamma-CD. The
      particular site substitution of the hydroxy group can produce changes in the
      hydroxyPAH fluorescence spectrum, and the effect of optical filter selection was
      studied for the LIF detection. The mass detection limits were in the (0.08-0.5) x
      10(-15) mol range. To our knowledge, this is the first report of the separation
      of metabolic products of PAHs (and several positional isomers) using gamma-CD and
      micellar electrokinetic chromatography.

PMID- 9604335
TI  - Direct determination of biogenic amines in wine by integrating continuous flow
      clean-up and capillary electrophoresis with indirect UV detection.
AB  - A flow-injection manifold for automating the determination of biogenic amines in
      wine using capillary electrophoresis (CE) with indirect UV detection was
      developed. The ensuing method involves clean-up and solid-phase extraction (SPE)
      of the target analytes in the sample. Various treatments involving different SPE
      minicolumns were tested and compared. The C18 minicolumn was chosen to
      concentrate the amines following addition of ammonium chloride and ammonium
      hydroxide as buffer to neutralize them. Additions of amine standards were used to
      determine recoveries. Biogenic amines can be separated and detected after SPE
      with limits of detection in the range 0.05-0.1 microgram ml-1 by using 4 mM
      copper(II) sulphate, formic acid and 18-crown-6 as running buffer. All the amines
      studied are eluted within 15 min under the optimum conditions established. The
      overall process was successfully used to identify biogenic amines in various
      types of wine from different Spanish regions.

PMID- 9604336
TI  - Cationic beta-cyclodextrin derivative for chiral separations.
AB  - A novel hepta-substituted beta-cyclodextrin bearing the methoxyethylamine group
      linked to the upper cyclodextrin rim was successfully used as a chiral selector
      for enantiomeric separation of non-steroidal anti-inflammatory drugs (NSAIDs) and
      phenoxypropionic acid herbicides (PPAHs). Separation parameters such as pH and
      concentration were found to have major influences on enantiomeric resolution of
      the NSAIDs and PPAHs. Results indicate that heptakis(6-methoxyethylamine-6-deoxy)
      beta-cyclodextrin [beta-CD-OMe (VII)] performs exceptionally well for the
      enantiomeric resolution of NSAIDs: indoprofen and fenoprofen (Rs = 11 and 14,
      respectively). In addition, baseline enantiomeric separation of a mixture of six
      pairs of PPAHs was achieved in under 30 min. Compared to other cationic beta
      cyclodextrins reported in the literature, the beta-CD-OMe (VII) showed improved
      selectivity for both classes of the aforementioned anionic racemates.

PMID- 9604337
TI  - Multidimensional counter-current chromatographic system and its application.
AB  - A multidimensional counter-current chromatographic system was set up for the
      first time with two sets of high-speed counter-current chromatography
      instruments. This system was successfully applied to the preparative separation
      of isorhamnetin, kaempferol and quercetin from crude flavone aglycones of Ginkgo
      biloba L. and Hippophae rhamnoides L. with a two-phase solvent system composed of
      chloroform-methanol-water (4:3:2, v/v/v).

PMID- 9604338
TI  - Metabolism of carbofuran by Aspergillus niger and Fusarium graminearum.
AB  - Metabolism of carbofuran in pure liquid cultures of A. niger and F. graminearum
      was investigated. Carbofuran and its metabolites were analyzed by HPLC and TLC.
      The average recoveries of carbofuran, 3-hydroxycarbofuran, 3-ketocarbofuran, and
      3-ketocarbofuran phenol from fungi media were found to be 88.65, 86.19, 75.48,
      and 80.48%, while their detection limits were 0.035, 0.031, 0.015 and 0.140 ppm,
      respectively. The data showed that A. niger was capable of degrading carbofuran
      more faster than F. graminearum. Carbofuran disappeared biexponentially from the
      liquid culture media of both fungi. The terminal half-life values of carbofuran
      were 10.4 and 12 days in the media of A. niger and F. graminearum, respectively.
      The amounts of carbofuran reached 15.56 and 19.71% of the applied dose after 21
      days in case of A. niger and F. graminearum, respectively. Carbofuran was
      biotransformed to 3-hydroxycarbofuran, 3-ketocarbofuran, and 3-ketocarbofuran
      phenol. The percentages of the major metabolite, 3-hydroxycarbofuran were 47.72
      and 7.77% in case of A. niger and F. graminearum after 21 days, respectively.

PMID- 9604339
TI  - Personal and environmental air sampling of methyl bromide during experimental
      greenhouse fumigation.
AB  - In this investigation methyl bromide, a widely used soil fumigant, was
      investigated with respect to workers exposure and environmental fortification at
      the greenhouses of Thessaloniki area, Northern Greece. By means of personal and
      environmental air sampling through charcoal, methyl bromide concentration was
      measured by gas chromatography using a capillary OV-1 column at 45 degrees C and
      flame ionization detector (FID). Personal air sampling for two workers showed
      that the levels of exposure to methyl bromide were 89 and 92 mg/m3 respectively.
      These values exceeded the safety limits. The mean maximum and mean minimum
      concentrations in the environmental air samples inside the greenhouse, for 8
      hours duration, were 142 mg/m3 and 4 mg/m3, respectively. These concentrations
      were determined within four and eleven days after the application of methyl
      bromide.

PMID- 9604340
TI  - Some applications of solid phase micro extraction (SPME) in the analysis of
      pesticide residues in food.
AB  - The Solid Phase Micro-Extraction (SPME) technique was applied to analyze
      chlorpropham in potatoes and amitraz in honey. The homogenized sample, suspended
      in water and stirred, was extracted with a 100 microns thick polidimetylsiloxane
      fiber and desorbed into the injection port of a gas chromatograph/mass
      spectrometer (quadrupole) operating in single ion monitoring. Sensitivities down
      to 0.01 mg/Kg and linear responses in the range of 0.01-0.1 mg/Kg were obtained.
      The results of SPME pesticide residue analysis in potatoes corresponded to those
      obtained with a traditional multiresidue method.

PMID- 9604341
TI  - The effect of compression ratio and release time on the categorical rating of
      sound quality.
AB  - Two experiments were carried out to determine how manipulating the compression
      ratio and release time of a single-band wide dynamic range hearing aid affects
      sound quality. In experiment I, compression ratio was varied over the range from
      linear to 10:1 (low compression threshold, attack time = 5 ms, release time = 200
      ms). In experiment II, compression ratios of 1.5, 2, and 3:1 were combined with
      release times of 60, 200, and 1000 ms (attack time = 5 ms). Twenty listeners with
      sensorineural hearing loss rated the clarity, pleasantness, background noise,
      loudness, and the overall impression of speech-in-noise (Ventilation, Apartment,
      Cafeteria) processed through a compression hearing aid. Results revealed that
      increasing compression ratio caused decreases in ratings on all scales.
      Increasing release time caused ratings of pleasantness to increase, and ratings
      of background noise and loudness to decrease. At the 3:1 compression ratio,
      increasing the release time caused increases in ratings of clarity, pleasantness,
      and overall impression, and a decrease in background noise. Significant
      correlations were found between scales. Regression analysis revealed that the
      contributions of the scales of clarity, pleasantness, background noise, and
      loudness to the prediction of overall impression differed as a function of the
      competing noise condition.

PMID- 9604342
TI  - Focusing and steering through absorbing and aberrating layers: application to
      ultrasonic propagation through the skull.
AB  - The time-reversal process is applied to focus pulsed ultrasonic waves through the
      human skull bone. The aim here is to treat brain tumors, which are difficult to
      reach with classical surgery means. Such a surgical application requires precise
      control of the size and location of the therapeutic focal beam. The severe
      ultrasonic attenuation in the skull reduces the efficiency of the time reversal
      process. Nevertheless, an improvement of the time reversal process in absorbing
      media has been investigated and applied to the focusing through the skull [J.-L.
      Thomas and M. Fink, IEEE Trans. Ultrason. Ferroelectr. Freq. Control 43, 1122
      1129 (1996)]. Here an extension of this technique is presented in order to focus
      on a set of points surrounding an initial artificial source implanted in the
      tissue volume to treat. From the knowledge of the Green's function matched to
      this initial source location a new Green's function matched to various points of
      interest is deduced in order to treat the whole volume. In a homogeneous medium,
      conventional steering consists of tilting the wave front focused on the
      acoustical source. In a heterogeneous medium, this process is only valid for
      small angles or when aberrations are located in a layer close to the array. It is
      shown here how to extend this method to aberrating and absorbing layers, like the
      skull bone, located at any distance from the array of transducers.

PMID- 9604343
TI  - An adaptive noise reduction stethoscope for auscultation in high noise
      environments.
AB  - Auscultation of lung sounds in patient transport vehicles such as an ambulance or
      aircraft is unachievable because of high ambient noise levels. Aircraft noise
      levels of 90-100 dB SPL are common, while lung sounds have been measured in the
      22-30 dB SPL range in free space and 65-70 dB SPL within a stethoscope coupler.
      Also, the bandwidth of lung sounds and vehicle noise typically has significant
      overlap, limiting the utility of traditional band-pass filtering. In this study,
      a passively shielded stethoscope coupler that contains one microphone to measure
      the (noise-corrupted) lung sound and another to measure the ambient noise was
      constructed. Lung sound measurements were made on a healthy subject in a
      simulated USAF C-130 aircraft environment within an acoustic chamber at noise
      levels ranging from 80 to 100 dB SPL. Adaptive filtering schemes using a least
      mean-squares (LMS) and a normalized least-mean-squares (NLMS) approach were
      employed to extract the lung sounds from the noise-corrupted signal.
      Approximately 15 dB of noise reduction over the 100-600 Hz frequency range was
      achieved with the LMS algorithm, with the more complex NLMS algorithm providing
      faster convergence and up to 5 dB of additional noise reduction. These findings
      indicate that a combination of active and passive noise reduction can be used to
      measure lung sounds in high noise environments.

PMID- 9604344
TI  - Spectral-ripple representation of steady-state vowels in primary auditory cortex.
AB  - Responses to various steady-state vowels were recorded in single units in the
      primary auditory cortex (AI) of the barbiturate-anaesthetized ferret. Six vowels
      were presented (/a/, /epsilon/, 2 different /i/'s, and 2 different /u/'s) in a
      natural voiced and a synthetic unvoiced mode. In addition, the responses to
      broadband stimuli with a sinusoidally shaped spectral envelope (called ripple
      stimuli) were recorded in each cell, and the response field (RF), which consists
      of both excitatory and inhibitory regions, was derived from the ripple transfer
      function. We examined whether the vowel responses could be predicted using a
      linear ripple analysis method [Shamma et al., Auditory Neurosci. 1, 233-254
      (1995)], i.e., by cross correlating the RF of the single unit, and the smoothed
      spectral envelope of the vowel. We found that for most AI cells (71%) the
      relative responses to natural vowels could be predicted on the basis of this
      method. Responses and prediction results for unvoiced and voiced vowels were very
      similar, suggesting that the spectral fine structure may not play a significant
      role in the neuron's response to the vowels. Predictions on the basis of the
      entire RF were significantly better than based solely on best frequency (BF) (or
      "place"). These findings confirm the ripple analysis method as a valid method to
      characterize AI responses to broadband sounds as we proposed in a previous paper
      using synthesized spectra [Shamma and Versnel, Auditory Neurosci. 1, 255-270
      (1995)].

PMID- 9604345
TI  - Within-channel gap detection using dissimilar markers in cochlear implant
      listeners.
AB  - Temporal gap detection thresholds were measured between perceptually dissimilar
      electrical markers in cochlear implant listeners. Both markers were presented to
      the same electrode pair. The amplitude and pulse rate of the first marker were
      fixed, and gap thresholds were measured as a function of either the pulse rate or
      the amplitude of the second marker. In either case, U-shaped functions were
      obtained, with lowest gap thresholds occurring when the two markers were similar
      in both amplitude and pulse rate. Because the two markers were presented to the
      same electrode pair, the data cannot be accounted for on the basis of across
      channel interactions. It is hypothesized that when different markers are used,
      the perceptual discontinuity from the first marker to the second is similar to
      the sensation of a brief gap, and dominates the gap detection process. Thus, gap
      threshold functions with electrically dissimilar markers serve more as indicators
      of perceptual distance between the markers and less as measures of temporal
      resolution.

PMID- 9604346
TI  - Analysis of the performance of a model-based optimal auditory signal processor.
AB  - Traditionally, psychophysical data have been predicted either by constructing
      models of the peripheral auditory system or by applying signal detection theory
      (SDT). Frequently, the theoretical detection performance predicted by SDT is
      greater than that observed experimentally and a nonphysiologically based
      "internal noise" source is often added to the system to compensate for the
      discrepancy. A more appropriate explanation may be that traditional SDT
      approaches either incorporate little or no physiology or make simplifying
      assumptions regarding the density functions describing the physiological data. In
      the work presented here, an integrated approach, which combines SDT and a
      physiologically based model of the human auditory system, is proposed as an
      alternate method of quantifying detection performance. To validate this approach,
      the predicted detection performance for a simultaneous masking task is compared
      to predictions obtained from traditional methods and to experimental data.
      Additionally, the sensitivity of the integrated method is thoroughly
      investigated. The results suggest that by combining SDT with a physiologically
      based auditory model, thereby capitalizing on the strengths of each individual
      method, the previously observed discrepancies can be partially explained as the
      result of physical processes inherent in the auditory system rather than
      unspecified "internal noise" and more accurate predictions of psychophysical
      behavior can be obtained.

PMID- 9604347
TI  - Beneficial effects of notched noise on intensity discrimination in the region of
      the "severe departure".
AB  - Intensity discrimination for a 6-kHz sinusoidal pedestal was measured in quiet
      and in the presence of a noise background. In the first experiment, the level of
      a 30-ms pedestal was fixed at 45 dB SPL and presented in the temporal and
      spectral center of a 110-ms notched noise. For a noise spectrum level of between
      0 and 15 dB the noise produced a substantial reduction in the Weber fraction,
      i.e., an improvement in detectability, compared to the condition without the
      noise. The second experiment showed that, unlike the situation with notched
      noise, narrow-noise produced no performance improvement, suggesting that the
      effect is dependent on noise frequency components outside the critical band of
      the pedestal. The third experiment showed that the improvement also occurred for
      a 6-ms pedestal presented in a 10-ms gap between two bursts of notched noise. The
      experiment rules out an explanation for the effect of the noise in terms of
      suppression on the basilar membrane. Finally, the effect was shown to decrease as
      the gap between the noise bursts was increased, in a manner at least broadly
      consistent with the decay of the temporal excitation pattern. It is suggested
      that the improvement in intensity discrimination in notched noise is due to an
      across-frequency comparison mechanism similar to "profile analysis," perhaps
      operating on a temporally smoothed central representation of the stimulus.

PMID- 9604348
TI  - Auditory filter nonlinearity at 2 kHz in normal hearing listeners.
AB  - Auditory filters broaden with increasing level. Using a recently developed method
      of fitting filter shapes to notched-noise masking data that explicitly models the
      nonlinear changes in filter shape across level, results at 2 kHz from 9 listeners
      over a wide range of levels and notch widths are reported. Families of
      roex(p,w,t) filter shapes lead to models which account well for the observed
      data. The primary effect of level is a broadening in the tails of the filter as
      level increases. In all cases, models with filter parameters depending on probe
      level fit the data much better than masker-dependent models. Thus auditory filter
      shapes appear to be controlled by their output, not by their input. Notched-noise
      tests, if performed at a single level, should use a fixed probe level. Filter
      shapes derived in this way, and normalized to have equal tail gain, are highly
      reminiscent of measurements made directly on the basilar membrane, including the
      degree of compression evidenced in the input-output function.

PMID- 9604349
TI  - Modeling interaural-delay sensitivity to frequency modulation at high
      frequencies.
AB  - Interaural-delay sensitivity to high-frequency (> or = 3 kHz) sinusoidal
      frequency-modulated (SFM) tones is examined for rates from 25 to 800 Hz and
      depths of -12 to 18 dB. Comparison is made to thresholds obtained for sinusoidal
      amplitude-modulated (SAM) tones for the same observers and modulation rates. Both
      SAM and SFM threshold-by-rate functions are U-shaped with optimum sensitivity to
      SFM tones occurring at higher rates (fm = 200-400 Hz) compared to those for SAM
      tones (fm = 100-200 Hz). Effects of modulation depth were examined for rates from
      50 to 300 Hz. In all cases thresholds improved considerably with increasing
      modulation depth. It is also shown that a hybrid dichotic signal composed of an
      SFM tone presented to one ear and an SAM tone to the other, can perceptually fuse
      and be lateralized, with the contingency that both stimuli have equal modulation
      rates but not necessarily equal carrier frequencies. Using bandpass noise to
      restrict off-frequency listening, it was shown that for this stimulus, observers
      can use information from filters either below or above the carrier frequency.
      Consistent with FM-to-AM conversion from cochlear bandpass filtering, several
      important differences between the SAM- and SFM-tone data can be predicted from a
      nonstationary stochastic model of binaural interaction whose parameters are
      uniquely determined from the SAM-tone data.

PMID- 9604350
TI  - Forward masked excitation patterns in multielectrode electrical stimulation.
AB  - Across-channel interactions in multi-electrode cochlear implant patients may be
      critical to their performance in the natural auditory environment. One measure of
      channel interaction can be obtained using forward masking. The patterns of
      threshold shift were obtained as a function of the separation between masker and
      probe electrode pairs in four Nucleus-implanted patients with varying levels of
      speech recognition. In the three subjects with better speech recognition (N4, N7,
      and N13), the masking patterns showed the least parameter dependence. In the
      subject with the lowest speech scores (N3), the masking patterns showed the
      greatest dependence on masker level and on probe delay. Masking as a function of
      masker level also reflected these differences: N3's functions showed the greatest
      changes for different probe delays. Similar rates of recovery were observed in
      the three good performers (time constant approximately 70 ms). In contrast,
      subject N3's recovery function shows a more rapid recovery. These data indicate
      that channel interaction is individually variable and parameter dependent, both
      of which may play a role in the perception of dynamic stimuli in the natural
      auditory environment.

PMID- 9604351
TI  - The masking-level difference in low-noise noise.
AB  - In experiment 1 NoSo and NoS pi thresholds for a 500-Hz pure tone were obtained
      in a low-fluctuation masking noise and a high-fluctuation masking noise for six
      normal-hearing listeners. The noise bandwidth was 10 Hz. In agreement with
      previous investigations, the NoSo thresholds were lower in low-fluctuation noise
      than in high-fluctuation noise. For three listeners, NoS pi thresholds were
      similar for the two types of noise, while for the other three listeners, Nos pi
      thresholds were higher for low-fluctuation noise than for high-fluctuation noise.
      In experiment 2, the masker was created by amplitude modulating a 500-Hz pure
      tone by a 0-10-Hz low-pass noise. The degree of masker fluctuation was controlled
      by adjusting the average modulation depth (100%, 63%, 40%, and 25%). The signal
      was a 10-Hz-wide noise centered on 500 Hz. Results were similar to those of
      experiment 1: for the NoSo conditions, signal detection improved with decreasing
      degree of fluctuation, and for NoS pi conditions, the results were subject
      dependent. For three listeners, NoS pi thresholds were again similar in the two
      types of noise, while for the other three listeners, NoS pi thresholds were again
      higher in low-fluctuation noise than in high-fluctuation noise. The results
      showed that a high degree of masker fluctuation sometimes facilitates NoS pi
      detection. It is possible that the binaural detection mechanism utilizes the
      relatively good signal-to-noise ratios that occur in the low power or "dip"
      regions of fluctuating masker waveforms.

PMID- 9604352
TI  - The influence of stimulus envelope and fine structure on the binaural masking
      level difference.
AB  - A masking level difference (MLD) paradigm was used to investigate the influence
      of stimulus envelope and stimulus fine-structure characteristics on monaural and
      binaural hearing. The degree of masker envelope fluctuation was manipulated by
      selecting narrow-band noises (50 Hz) on a continuum of values of the normalized
      fourth moment of the envelope. The noises were specified as low-noise noise
      (LNN), medium-noise noise (MNN), and high-noise noise (HNN). Fine-structure cues
      were studied by measuring thresholds at 500 and 4000 Hz, regions in which the
      availability of such cues to the auditory system differ substantially. In
      addition, thresholds were measured for Gaussian noise maskers (GN) and for
      maskers having a flat magnitude spectrum, termed equal-magnitude noise (EMN)
      maskers. The results indicated lower NoSo thresholds for LNN than for the other
      four masker types. Furthermore, there were no differences in threshold for
      maskers having moderate and high degrees of envelope fluctuation (MNN and HNN).
      The NoS pi thresholds were not significantly different across masker type and
      were characterized by large individual differences among the seven listeners. The
      results are considered in relation to models of monaural and binaural processing.
      Consistent with previous reports, the results indicate that binaural detection
      depends on interaural differences in the stimulus envelope and fine structure at
      low frequencies and changes in the envelope at high frequencies.

PMID- 9604353
TI  - Masker fluctuation and the masking-level difference.
AB  - Previous work suggests that, for some listeners, masker fluctuation may be
      advantageous for NoS pi detection. This study tested the hypothesis that the
      benefit of masker fluctuation to binaural analysis is based on the ability to
      take advantage of epochs of low masker energy in the fluctuating masker where the
      cues underlying binaural signal detection are more salient. The hypothesis was
      evaluated using the time-domain version of COSS analysis derived by Buus et al.
      [J. Acoust. Soc. Am. 99, 2288-2297 (1996)] which measures the perceptual weight
      applied by a listener within a relatively brief time window as a function of the
      masker level during the window. The results indicated a dependency of signal
      detection on short-term masker level in the NoS pi condition but not in the NoSo
      condition. This finding supports a new perspective indicating that binaural
      signal detection depends upon the envelope of a masker in a way that is
      fundamentally different from that typically associated with monaural detection.

PMID- 9604354
TI  - Spontaneous classification of complex tones at high and ultrasonic frequencies in
      the bat, Megaderma lyra.
AB  - Megaderma lyra, a bat species using harmonically structured calls for
      echolocation, exploits the spectral content of its echoes for texture
      discrimination. It is the aim of the present study to test according to which
      sensory qualities harmonic complex tones are spontaneously classified by this
      bat. The applied experimental paradigm is especially adapted to the preference of
      M. lyra to use absolute pitch cues. Three animals were trained in a 2-AFC
      procedure to classify three-component stimuli as low or high, with all their
      harmonics below or above a pure tone reference of 33 kHz, respectively. Later,
      the original tones were interspersed with "incomplete" test stimuli, with their
      fundamentals (and lower harmonics) missing. These were ambiguous in that their
      possible virtual, i.e., collective pitches were below the reference whereas their
      pure tone pitches were above it. Bat 1 classified 22 of 23 test stimuli with
      missing fundamentals between 5.3 and 28.3 kHz according to their collective
      pitches, whereas bat 2 judged all presented ambiguous tones on the basis of their
      pure tone pitches. Bat 3 failed the pitch control criterion which is why in this
      case results cannot be interpreted unequivocally. The implications of these
      findings are discussed with respect to the bats' behavioral context, as well as
      to psychoacoustical models of the formation of the pitch of complex tones.

PMID- 9604355
TI  - The pitch of a mistuned harmonic: evidence for a template model.
AB  - A harmonic of a periodic complex tone can be heard out as a separate entity if
      the harmonic is slightly mistuned from its correct frequency. Pitch matching
      experiments show that the pitch of such a mistuned harmonic differs
      systematically from its frequency. The shift in pitch is found to be an
      exaggeration of the frequency mistuning. This article considers two classes of
      model for the pitch shift. In the first class are tonotopically local interaction
      models which attribute the pitch shift to interactions between the mistuned
      harmonic and neighboring harmonics, where the neighborhood is established by
      peripheral filtering. The second class of model attributes the pitch shift to a
      contrast between the mistuned harmonic and a broadband harmonic template. This
      article describes six pitch matching experiments using complex tones having
      spectral gaps, strategically chosen to compare local interaction and template
      models. The results show that when a competition is set up between local
      interactions and a template, the template proves to be dominant. A parallel
      between the pitch shifts of mistuned harmonics and periodicity pitch, also
      attributed to a harmonic template, is seen as the frequency range of the mistuned
      harmonic is changed. Tonotopically local influences are evident in several
      experiments, but they are of secondary importance.

PMID- 9604356
TI  - Monaural phase discrimination by macaque monkeys: use of multiple cues.
AB  - Research examining the discrimination of monaural phase change has suggested that
      temporal envelope shape, which varies with phase, may be an important cue. Much
      of that research employed stimuli consisting of three components, a center
      frequency (Fc), which is varied in phase, and an upper and lower sideband
      separated from the carrier by some frequency (delta F). As the phase of the
      center component is varied, both temporal envelope and temporal fine structure
      change. The present research explored the salience of both envelope and fine
      structure as cues in a phase discrimination task. Monkeys were trained to report
      detection of a change from a three-tone complex with 90 degrees starting phase
      for the center component to one in which the starting phase was smaller. In
      general, for the values of Fc tested, thresholds for phase change decreased as
      delta F increased. When tested with comparison stimuli that had a temporal
      envelope closely matched to that of the standard, but 0 degree starting phase,
      subjects had difficulty discriminating these stimuli from the standard for
      smaller delta F, but readily discriminated them at larger delta F values. These
      findings suggest that temporal envelope is a critical cue in discrimination of
      three-tone complexes on the basis of the starting phase of the center component
      at small values of delta F, but that other cues are used at larger delta F
      values.

PMID- 9604357
TI  - Lateralization and binaural discrimination of patients with pontine lesions.
AB  - Lateralization and just-noticeable difference (jnd) measurements relative to the
      center were tested in a large group of patients with pontine lesions caused
      either by stroke or multiple sclerosis. Stimuli included binaural clicks, and low
      and high-frequency narrow-band noise bursts. Two major types of abnormalities
      were revealed in the lateralization performances: perception of all stimuli,
      regardless of interaural differences (time and/or level) in the center of head
      (center-oriented), or lateralization of all stimuli to one side or the other of
      the head (side-oriented). The only significant correlation between jnd and
      lateralization performances was that an elevated jnd was always manifested in
      abnormal lateralization, while abnormality in lateralization did not necessarily
      indicate an abnormal jnd. Center-oriented lateralization was observed either for
      both interaural differences or only for one of them, and was found in both MS and
      stroke patients. All side-oriented stroke patients were similarly unable to
      center binaural stimuli for both time and level cues, whereas only one MS patient
      had this abnormality for interaural time differences, while his level performance
      was normal. More abnormalities were detected in the narrow band stimuli tests,
      although in some cases performance was more degraded for click stimuli.
      Lateralization tasks with high-frequency stimuli were more sensitive detectors of
      abnormality than jnd for any kind of stimulus, or lateralization tasks with low
      frequency stimuli or clicks.

PMID- 9604358
TI  - Spectro-temporal factors in two-dimensional human sound localization.
AB  - This paper describes the effect of spectro-temporal factors on human sound
      localization performance in two dimensions (2D). Subjects responded with saccadic
      eye movements to acoustic stimuli presented in the frontal hemisphere. Both the
      horizontal (azimuth) and vertical (elevation) stimulus location were varied
      randomly. Three types of stimuli were used, having different spectro-temporal
      patterns, but identically shaped broadband averaged power spectra: noise bursts,
      frequency-modulated tones, and trains of short noise bursts. In all subjects, the
      elevation components of the saccadic responses varied systematically with the
      different temporal parameters, whereas the azimuth response components remained
      equally accurate for all stimulus conditions. The data show that the auditory
      system does not calculate a final elevation estimate from a long-term (order 100
      ms) integration of sensory input. Instead, the results suggest that the auditory
      system may apply a "multiple-look" strategy in which the final estimate is
      calculated from consecutive short-term (order few ms) estimates. These findings
      are incorporated in a conceptual model that accounts for the data and proposes a
      scheme for the temporal processing of spectral sensory information into a dynamic
      estimate of sound elevation.

PMID- 9604359
TI  - Acoustic, aerodynamic, physiologic, and perceptual properties of modal and vocal
      fry registers.
AB  - The purpose of the study was to examine the acoustic, aerodynamic, physiologic,
      and perceptual characteristics of modal and vocal fry production. Twenty normal
      speakers (10 males, 10 females) participated in the study. Speech material
      included four sustained vowels (/i/, /a/, /ae/, /u/), and syllable strings of
      /pi/ repetitions produced in both modal and vocal fry registers. Acoustic data
      (fundamental frequency, jitter, shimmer, and signal-to-noise ratio), aerodynamic
      data (airflow and air pressure), and electroglottographic (EGG) data were
      obtained simultaneously. Results demonstrated considerable differences across
      voice parameters for the modal and vocal fry registers. Fundamental frequency was
      significantly lower in vocal fry than in modal register for both males and
      females, however, significant gender differences existed only in modal register.
      For both males and females, measurements of jitter and shimmer were significantly
      higher and signal to noise ratio was significantly lower in vocal fry. In
      addition, airflow rate in modal register was almost three times as high as the
      airflow rate in vocal fry register during sustained vowel production. During
      syllable string production, subglottal air pressure values in modal register were
      approximately 1.5 times higher than that in the vocal fry register. In general,
      these data emphasize that the aeromechanical mechanisms of vocal fold vibratory
      behavior are substantially different between modal and vocal fry registers. A
      model of vocal fry phonation is presented to account for the present results.

PMID- 9604360
TI  - "How to milk a coat:" the effects of semantic and acoustic information on phoneme
      categorization.
AB  - This study examined the effect of sentence context and local acoustic structure
      on phoneme categorization. Target stimuli from a 10-step GOAT-COAT continuum,
      differing only on a temporal cue for voice onset time (VOT), were embedded in
      carrier sentences that biased interpretation toward either "goat" or "coat."
      While subjects listened to the sentences they also responded as quickly as
      possible to a visual probe by indicating whether the probe matched the target
      stimulus they heard. Results showed that the interaction of VOT and sentence
      context significantly affected both identification and RT for stimuli near the
      perceptual boundary; the identification function showed a boundary shift in favor
      of the biased context and peak response times for each context reflected the
      shifted identification boundaries. In addition, response times were faster for
      identification of stimuli near the category boundary when responses were
      congruent, rather than incongruent with the sentence context. The response time
      differences for congruent versus incongruent responses in the boundary region are
      interpreted as depending on the results of initial phonological analysis;
      potentially ambiguous categorizations may be subject to additional evaluation in
      which a context-congruent response is both preferred and available earlier.

PMID- 9604362
TI  - An analysis of the effect of basilar membrane nonlinearities on noise
      suppression.
AB  - Computational models of the peripheral auditory system have largely modeled
      basilar membrane (BM) mechanics as a linear filter-bank-like entity. Recent
      mathematical work on the nature of auditory system noise suppression allows us to
      analyze and argue for the incorporation of BM nonlinearities into these models.
      This analysis shows that vowel perception improves with increasing presence of BM
      nonlinearities whereas consonant perception degrades with increasing influence of
      BM nonlinearities. Experimental results on tones and real speech corrupted by
      noise corroborate the analysis as well as suggest a novel approach to speech
      processing.

PMID- 9604361
TI  - Auditory-visual speech recognition by hearing-impaired subjects: consonant
      recognition, sentence recognition, and auditory-visual integration.
AB  - Factors leading to variability in auditory-visual (AV) speech recognition include
      the subject's ability to extract auditory (A) and visual (V) signal-related cues,
      the integration of A and V cues, and the use of phonological, syntactic, and
      semantic context. In this study, measures of A, V, and AV recognition of medial
      consonants in isolated nonsense syllables and of words in sentences were obtained
      in a group of 29 hearing-impaired subjects. The test materials were presented in
      a background of speech-shaped noise at 0-dB signal-to-noise ratio. Most subjects
      achieved substantial AV benefit for both sets of materials relative to A-alone
      recognition performance. However, there was considerable variability in AV speech
      recognition both in terms of the overall recognition score achieved and in the
      amount of audiovisual gain. To account for this variability, consonant confusions
      were analyzed in terms of phonetic features to determine the degree of redundancy
      between A and V sources of information. In addition, a measure of integration
      ability was derived for each subject using recently developed models of AV
      integration. The results indicated that (1) AV feature reception was determined
      primarily by visual place cues and auditory voicing + manner cues, (2) the
      ability to integrate A and V consonant cues varied significantly across subjects,
      with better integrators achieving more AV benefit, and (3) significant intra
      modality correlations were found between consonant measures and sentence
      measures, with AV consonant scores accounting for approximately 54% of the
      variability observed for AV sentence recognition. Integration modeling results
      suggested that speechreading and AV integration training could be useful for some
      individuals, potentially providing as much as 26% improvement in AV consonant
      recognition.

PMID- 9604363
TI  - Acoustic anisotropy in bovine cancellous bone.
AB  - This paper presents the experimental results on the acoustic anisotropy in bovine
      cancellous bone. The propagation of both fast and slow longitudinal waves in
      bovine cancellous bone was experimentally examined in relation to the structural
      anisotropy, or the trabecular arrangement. Propagation speeds of the fast and
      slow waves were measured as a function of the propagation angle to the trabecular
      alignment, and theoretically estimated by use of Biot's theory for an isotropic
      medium.

PMID- 9604364
TI  - Comments on "A re-examination of risk estimates from the NIOSH Occupational Noise
      and Hearing Survey" [J. Acoust. Soc. Am. 101, 950-963 (1997)].

PMID- 9604365
TI  - Species differences of distortion-product otoacoustic emissions: comment on
      "Interpretation of distortion product otoacoustic emission measurements. I. Two
      stimulus tones" [J. Acoust. Soc. Am. 102, 413-429 (1997)].

PMID- 9604366
TI  - Social and economic dimensions of environmental policy: lead poisoning as a case
      study.

PMID- 9604367
TI  - Health services research and systemic lupus erythematosus: a reciprocal
      relationship.
AB  - Many other statistical and epidemiologic approaches have been used in studies of
      systemic lupus erythematosus. Many of these, such as multivariate analysis and
      cost-benefit analysis, have substantially added to our understanding of the
      disease. However, in these instances it has been a clear application of the
      technique to a clinical problem. In the four areas I described, there was a
      convergence of clinical dilemmas and methodologic improvements, with the clinical
      problem actually contributing to the development of the methodologic technique
      used to address the question. In conclusion, major methodologic advancements in
      health services research and clinical epidemiology have developed pari passu with
      studies of the natural history of systemic lupus erythematosus. In some
      circumstances the clinical questions drove methodologic innovation and in other
      cases the methodologic studies were rapidly adopted and adapted to clinical
      investigation. It is unlikely that this was happenstance. We can anticipate that
      future investigations in lupus will utilize innovative techniques in health
      services research.

PMID- 9604368
TI  - Current perspectives on the function of sleep.

PMID- 9604369
TI  - Animal fat and cholesterol may have helped primitive man evolve a large brain.

PMID- 9604370
TI  - Optimization and utilization of the atomic force microscope for living systems.

PMID- 9604371
TI  - Molecular image of a myosin motion.

PMID- 9604372
TI  - Looking at the bright side of photobleaching: analysis of intracellular protein
      dynamics by confocal microscopy.

PMID- 9604373
TI  - Imaging drug therapy and pH in gastrointestinal tissue with confocal and two
      photon microscopy.

PMID- 9604374
TI  - 3-D microscopy to assess bone healing around dental implants.

PMID- 9604375
TI  - Measurement of trabecular length in archaeological lumbar vertebrae using close
      range photogrammetry.

PMID- 9604376
TI  - Infectious disease electron microscopy for 30 years without negative incident ...
      why?

PMID- 9604377
TI  - Investigation of foreign substances in food.

PMID- 9604378
TI  - The effect of surface modification of mechanical aortic valves on
      thrombogenicity.

PMID- 9604379
TI  - Ultrastructural lesions in mammalian cells after neptunium-237 intoxication:
      radiological or chemical lesions?

PMID- 9604380
TI  - Quantitative backscattered electron imaging and analysis of urinary stones.

PMID- 9604381
TI  - Immune ultrastructural evidence of lymphocytic antigen binding by Lyme disease
      spirochetes.

PMID- 9604383
TI  - Human cerebellar cortex studied in scanning electron microscopy.

PMID- 9604382
TI  - Confocal laser scanning microscopy and scanning electron microscopy of cerebellar
      glomeruli.

PMID- 9604384
TI  - Apoptosis and cancer: a multiple technical approach to different experimental
      models.

PMID- 9604385
TI  - Immunogold staining for Bcl-xL and morphological analysis of rat and human
      vascular smooth muscle cells undergoing apoptosis induced by c-myc or
      staurosporine.

PMID- 9604386
TI  - Scanning electron microscopy and transmission electron microscopy aspects of the
      synergistic antitumor activity of vitamin C/vitamin K3 combinations against human
      T24 bladder carcinoma: another kind of cell death?

PMID- 9604387
TI  - Characterization of the early events in vitamin C and K3-induced death of human
      bladder tumor cells.

PMID- 9604388
TI  - Radiation-induced apoptosis in B lymphocytes and immunosuppression in chickens:
      its use in clinical diagnosis.

PMID- 9604389
TI  - Chemoradiotherapy for esophageal cancer.

PMID- 9604390
TI  - Centrosome instability in cells during aging.

PMID- 9604391
TI  - Confocal laser scanning microscopy of chondrocytes in vitro: cytoskeletal protein
      changes after quinolone treatment.

PMID- 9604393
TI  - Use of methylmethacrylate to study the microangioarchitecture of spleen and the
      diabetic retina in mice and rats.

PMID- 9604392
TI  - Scanning electron microscopic demonstration of surface and subsurface enzymes in
      rat endometrium during the estrous cycle.

PMID- 9604394
TI  - Laser-induced ultrastructural changes of neutrophils in lung inflammation.

PMID- 9604395
TI  - High-resolution electron microscopy of human enamel sections prepared with
      focused ion beam system.

PMID- 9604396
TI  - Comparative morphologic study of calcospherites between continuously growing
      teeth and uncontinuously growing teeth.

PMID- 9604397
TI  - Age-related changes in the remodeling of the nasoalveolar clivus of common
      chimpanzees as revealed through scanning electron microscopy.

PMID- 9604398
TI  - Bone growth rate and relative mineralization density during space flight.

PMID- 9604399
TI  - An electron microscopy study of the adherence of Bifidobacterium bifidum to human
      intestinal Caco-2 cells in vitro.

PMID- 9604400
TI  - Microstructure and chemical composition of human gallstones before and after
      dissolution: cathodoluminescence studies.

PMID- 9604401
TI  - Different technical approaches to the study of apoptotic micronuclei.

PMID- 9604402
TI  - Nuclear pore complex disassembly and nuclear envelope breakdown during mitosis
      may occur by both nuclear envelope vesicularisation and dispersion throughout the
      endoplasmic reticulum.

PMID- 9604403
TI  - The fine and three-dimensional observations on the basal plate surface and
      anchoring villi in mature human placenta.

PMID- 9604404
TI  - Localization of left-handed Z-RNA in the outer cortical secondary fiber cells of
      the adult dog crystalline lens.

PMID- 9604406
TI  - Primary care research: the MRC's proposals.

PMID- 9604405
TI  - R&D in primary care--an NHS priority.

PMID- 9604407
TI  - General practice research: deaths and entrances.

PMID- 9604408
TI  - An evaluation of practice nurses working with general practitioners to treat
      people with depression.
AB  - BACKGROUND: The diagnosis and treatment of depression constitutes a significant
      component of a general practitioner's workload. A pilot study has suggested that
      the practice nurse may have an important contribution to make in the care of
      patients with depression. AIM: To evaluate an extended role for practice nurses
      in improving the outcome of depression through two specially-designed interviews
      running in parallel. METHOD: Two naturalistic, random allocation studies took
      place concurrently over four months. Study 1 evaluated the effectiveness of
      standardized psychiatric assessment by a practice nurse and feedback of
      information to the general practitioner (GP). Study 2 evaluated the above
      assessment and feedback combined with nurse-assisted follow-up care. Twenty
      general practices participating in the Medical Research Council General Practice
      Research Framework took part in the study. Subjects included general practice
      attenders identified as depressed by their GP. The main outcome measures were a
      change in Beck Depression Inventory (BDI) scores and in the proportion of
      patients fulfilling DSM-III criteria for major depression. RESULTS: A total of
      577 patients were recruited; 516 [89% (95% CI = 86-92%)] were rated as depressed
      on the BDI and 474 [82% (95% CI = 79-85%)] met criteria for DSM-III major
      depression. Altogether, 524 (91%) patients completed follow-up at four months.
      All groups of patients showed improvement, but no difference in the rate of
      improvement was shown for the nurse intervention groups. BDI mean scores fell
      from 18.54 (95% CI = 17.53-20.06) to 11.53 (95% CI = 10.02-13.04) in Study 1, and
      from 21.01 (95% = CI 20.26-21.86) to 10.62 (95% CI = 9.73-11.51) in Study 2. The
      proportion of patients fulfilling criteria for DSM-III major depression in Study
      1 fell from 80% (95% CI = 73-87%) to 30% (95% CI = 22-38%), and in Study 2 from
      80% (95% CI = 76-84%) to 27% (95% CI = 23-31%). Prescription rates of
      antidepressant medication were higher than expected, ranging between 63% and 76%
      in the two studies. CONCLUSION: There was an increase in the rate of
      antidepressant prescription, but no additional benefit could be adduced for
      patients who received a nurse intervention.

PMID- 9604409
TI  - Everyday symptoms in childhood: occurrence and general practitioner consultation
      rates.
AB  - BACKGROUND: Fewer than 20% of all illnesses that occur in the home require the
      attention of a general practitioner (GP). Whether specific illnesses in children
      are more likely to need the attention of a GP is poorly understood, as is the
      influence of various other factors. Health diaries are the most suitable method
      of collecting comprehensive information about children's health problems at home
      and in general practice simultaneously. AIM: To investigate the occurrence of,
      and consultation rates for, specific symptoms in childhood in relation to age,
      sex, birth order, and place of residence of the child, and season of the year.
      METHOD: The parents of 1805 children kept a health diary over three weeks and
      recorded symptoms and consultation behaviour. The symptoms were later combined
      into illness episodes. RESULTS: Over three weeks, colds/flu (157/1000 children)
      and respiratory symptoms (114/1000 children) occurred most frequently. More young
      children (0-4 years) suffered from illness generally. Eleven per cent of all
      illness episodes required the attention of a GP. Consultation rates differed
      greatly according to symptoms. A GP was consulted most often for ear (36%) and
      skin (28%) problems, and least often for headaches (2%) and tiredness (1%).
      Regardless of symptoms, young children (0-4 years) were taken to a GP twice as
      often as older children (10-14 years). CONCLUSIONS: This study emphasizes the
      enormous amount of illness that occurs in children and the fact that more than
      80% of all illnesses are dealt with by parents without reference to the
      professional health care system.

PMID- 9604410
TI  - General practice patients' beliefs about their symptoms.
AB  - BACKGROUND: Patients' beliefs about symptoms are major influences on consultation
      and its consequences. However, little information is available about the beliefs
      of patients when they consult their general practitioner (GP). AIM: To describe
      and quantify the range of beliefs of patients about their symptoms before
      consultation, and to test the hypothesis that patients who attribute symptoms to
      stress or lifestyle would expect less benefit than others from physical medicine
      but more from lifestyle change and emotional support. METHOD: Interviews with 100
      patients attending one of two general practices were used to form a
      questionnaire, which was completed by 406 patients attending one of three general
      practices in contrasting areas of Greater London. This measured the frequency of
      specific beliefs about the causes of their symptoms and about effective forms of
      help. Patients were seen before their consultation. RESULTS: The most common
      aetiological beliefs concerned stress and lifestyle. In general, the mechanisms
      underlying symptoms were thought to be disturbances in bodily functioning rather
      than pathological processes. The most valued form of help was explanation and
      discussion of symptoms. Nevertheless, about half the patients expected benefit
      from medication and only slightly fewer from hospital investigation or treatment.
      Patients who attributed symptoms to stress or lifestyle were no less likely to
      expect help from medication or specialist referral, but they were more likely to
      see benefit in explanation and counselling or lifestyle change. CONCLUSIONS:
      These findings suggest hypotheses for future research into the effects that
      patients' attributions of their symptoms to stress and lifestyle have on their
      health care demands, emphasize the importance of routinely assessing patients'
      beliefs on consulting the GP, and provide information that can help to direct
      this assessment in the individual case.

PMID- 9604411
TI  - GP documentation of obesity: what does it achieve?
AB  - BACKGROUND: Obesity is a major and increasing health problem in the United
      Kingdom, and, until recently, the government health promotion package for general
      practice reimbursed general practitioners for documenting obesity. Despite poor
      evidence for effectiveness of interventions in primary care, documentation of
      obesity could possibly improve patient awareness and knowledge, or provide public
      health information. AIM: To assess patient perception of obesity and its health
      risk, and the accuracy of estimating obesity using patient information. METHOD:
      Subjects were consecutive attenders to a general practitioner (GP) at a single
      urban practice in the South and West Region. Outcome measures were 'measured'
      body mass index (BMI) calculated from measured weight and height, 'estimated' BMI
      using patient information, and patient perception of obesity and the health risks
      of obesity. RESULTS: There is good correlation between 'estimated' and 'measured'
      BMI (intraclass correlation 0.91). Estimated BMI is lower than measured BMI (mean
      0.77 lower), and the difference increases with age and level of BMI: for BMIs of
      < 20, 20-24.99, 25-29.99, and > or = 30 the mean differences (estimated-measured)
      were -0.06, -0.46, -0.98 and -1.72 respectively. Estimated obesity (BMI > 30) is
      reasonably sensitive (70%), specific (99%), and predictive (93% positive
      predictive value) of measured obesity (kappa 0.78). All obese subjects are aware
      that they are overweight, and most of them (78%, 95% confidence interval 66-88%)
      are aware that their weight is a health risk. CONCLUSION: Obese patients
      attending GPs' surgeries are likely to know if they are overweight, or could
      easily estimate from their knowledge of height and weight that they were
      overweight with reasonable accuracy. Obese subjects also know that their weight
      carries health risks. Thus, measurement of obesity in the general population is
      not likely to improve risk assessment or patient knowledge significantly. Without
      evidence for effective intervention or improved decision-making in primary care,
      reimbursement guidelines linked to the documentation of obesity in the population
      are probably an inefficient use of resources.

PMID- 9604412
TI  - Frequency of patients' consulting in general practice and workload generated by
      frequent attenders: comparisons between practices.
AB  - BACKGROUND: Patients who attend frequently may present a problem for general
      practitioners (GPs) in several ways. The frequency of patients' consulting,
      comparisons between practices, and the effect of frequent consulting on the
      clinical workload have not been quantified previously. AIMS: To examine the
      distribution of the number of consultations per patient in four general
      practices. To estimate the clinical workload generated by frequent attenders. To
      model the data to demonstrate the contribution of age, sex, and practice on the
      likelihood of attending frequently. METHOD: Analysis and modelling of a validated
      data set of date records of consultations collected routinely over a 41-month
      period from four practices in and around Leeds, representing 44,146 patients and
      470,712 consultations. RESULTS: A minority of patients consulted with extreme
      frequency. All practices had similar distributions but varied with respect to the
      numbers of frequent attenders, and the frequencies of their consulting. The most
      frequent 1% of attenders accounted for 6% of all consultations, and the most
      frequent 3% for 15% of all consultations. Females and older people were more
      likely to be frequent attenders. CONCLUSION: Frequent attenders have an important
      effect on GPs clinical workload. Between one in six and one in seven
      consultations are with the top 3% of attenders. Further research is needed to
      explain the behaviour underpinning frequent attendance in order to identify
      appropriate management strategies; such strategies could have an important effect
      on clinical workload.

PMID- 9604413
TI  - Can GPs audit their ability to detect psychological distress? One approach and
      some unresolved issues.
AB  - BACKGROUND: General practitioners (GPs) should be able to detect psychological
      distress in their patients. However, there is much evidence of underperformance
      in this area. The principle of clinical audit is the identification of
      underperformance and amelioration of its causes, but there appear to be few
      evaluated models of audit in this area of clinical practice. AIM: To evaluate the
      feasibility of auditing GPs' performance as detectors of psychological distress.
      Specific objectives were to test a model of the audit cycle in the detection of
      psychological distress by GPs; to research GP perceptions of prior audit activity
      in this area and the validity of the instruments used to measure GP performance;
      and to research GP perceptions of the value of this specific approach to the
      audit of their performance and the particular value of different aspects of the
      model in terms of its impact on clinician behaviour. METHOD: Prospective
      controlled study of an audit cycle of GP detection of psychological distress.
      Nineteen GP principals used a self-directed educational intervention involving
      measurement of their performance, followed by data feedback and review of
      selected videotaped consultations. Qualitative data on GP views of audit in this
      area of clinical activity were collected before and after the quantitative data
      collection. RESULTS: The study shows that the GP cohort had not previously
      considered auditing their performance as detectors of psychological distress.
      They found the instruments of measurement and the model of audit acceptable.
      However, they also suggested modifications that might be educationally more
      effective and make the audit more practical. These included smaller patient
      numbers and more peer contact. The implications of the study for a definitive
      model of audit in this area are discussed. CONCLUSION: Effective audit of GP
      performance in detection of psychological distress is possible using validated
      instruments, and GP performance can be improved by educational intervention. GPs
      in this study appear more motivated by individual case studies and reflection
      through video analysis on undiagnosed patients than by quantitative data feedback
      on their performance. This study therefore supports other evidence that clinical
      audit has most impact when quantitative data is coupled with clinical examples
      derived from patient review.

PMID- 9604414
TI  - Why do some patients not cash their prescriptions?
AB  - BACKGROUND: A small number of studies have used different methodologies to
      measure primary non-compliance, but they have not established the reasons for
      patients not cashing their prescriptions. It has been suggested that the number
      of uncashed prescriptions is a measure of the quality of doctor-patient
      communication, but this hypothesis remains untested. AIM: To establish the
      feasibility of obtaining data on a sensitive subject from patients by interview
      and to seek patients' reasons for not cashing prescriptions using qualitative
      data. METHOD: Questionnaire administered to 1000 consecutive patients attending
      surgery, followed by interview with those patients who indicated that they had
      not cashed the index prescription. RESULTS: The response rate was 93.5%. Twenty
      two patients were included in the study. There was wide variation in the number
      of uncashed prescriptions issued by each doctor (1-13). A total of nine out of 22
      patients reported that their medication was cheaper over the counter and obtained
      it in this way; 13 out of 22 did not obtain their medication. Five patients
      indicated that cost was a factor in not obtaining their medication. Other factors
      included the doctor's permission not to cash the prescription, poor understanding
      of the illness, and the wish to maintain control. CONCLUSION: It is feasible to
      ask patients about aspects of their behaviour that may indicate, or cause,
      difficulties in the doctor-patient relationship. Prescribing behaviour varies
      widely between doctors and, although cost is a factor in determining whether a
      prescription will be cashed, other variables, such as the patient's desire to
      maintain control over the illness, may be more important.

PMID- 9604415
TI  - Victims of violence and the general practitioner.
AB  - BACKGROUND: Violent crime is on the increase in Britain, with 17% of the 15
      million incidents of crime reported in 1991 being of a violent nature. Although
      there is some information on the role of accident and emergency departments for
      victims who sustain physical injury, little is known about the role of the
      general practitioner (GP) in managing the acute and longer-term sequelae of
      violence. AIM: To examine the links between experiencing physical of sexual
      assault and seeking help from GPs in London. METHOD: A cross-sectional survey of
      all adult attendees in one large group practice was carried out. The main outcome
      measures were prevalence of assault, reporting to the doctor and other people,
      and scores on the General Health Questionnaire (GHQ) and the Impact of Events
      scale. RESULTS: Of the 195 people who took part, 33 (17%) reported a physical or
      sexual assault in the previous year. Women were three times more likely than men
      to report any type of assault. Women rarely spontaneously disclosed these
      experiences to the GP and yet the experience of violence was associated with
      higher levels of distress, as measured on the GHQ and the Impact of Events Scale.
      CONCLUSIONS: Assault is a relatively common event in the lives of people who
      consult their GP. Doctors could help these patients through gaining an awareness
      of the problem and by fostering links with voluntary services, such as victim
      support schemes, which can provide support, practical assistance, and advice on
      compensation claims and legal procedures.

PMID- 9604416
TI  - Teenage health and the practice nurse: choice and opportunity for both?
AB  - Teenage health issues and the means to address them have caused increasing
      concern over recent years. This study investigated the involvement and training
      of practice nurses, the topics raised during consultations with teenagers, and
      the comfort of the practice nurses in dealing with these topics. Data were
      collected using a postal questionnaire survey (response rate 80.6%). Expansion of
      the role of the practice nurse in teenage health may be appropriate but needs to
      be supported by training.

PMID- 9604417
TI  - Patient satisfaction with referral to hospital: relationship to expectations,
      involvement, and information-giving in the consultation.
AB  - Information is needed as to how general practitioners (GPs) can best satisfy
      their patients when they are being referred to hospital. This study demonstrates
      the importance of involving patients in decision making and of giving them
      information.

PMID- 9604418
TI  - Sleep patterns of a rural elderly population.
AB  - A complaint of sleep disturbance may be subjective, requiring education and
      reassurance, but it may also indicate underlying morbidity. Elderly people expect
      to sleep six to eight hours each night. Many accept fragmentation of sleep and
      night-time waking as a normal part of ageing.

PMID- 9604419
TI  - Vocational training and beyond--listening to voices from a void.
AB  - This paper is written from the viewpoint of a doctor who has recently undergone
      general practice vocational training, and has first-hand experience of some of
      the opportunities, difficulties, and uncertainties facing doctors at this stage
      of their careers. The literature on vocational training and the issues concerning
      young doctors are explored in the light of concerns that recruitment into general
      practice is falling, that registrars may feel lost in a 'void' at the end of
      training, and that the 'new world' of post-training work brings problems for many
      new general practitioners (GPs). Instead of a traditional partnership, one of the
      authors (RB) chose a salaried, educationally oriented introduction to inner-city
      general practice. Some innovative, educational schemes, which are aiming to
      improve the appeal of general practice, are discussed.

PMID- 9604420
TI  - Genital warts and cervical screening.

PMID- 9604421
TI  - Primary care of patients with schizophrenia.

PMID- 9604422
TI  - Folic acid supplements.

PMID- 9604423
TI  - One-to-one teaching with pictures.

PMID- 9604424
TI  - Blepharitis.

PMID- 9604425
TI  - Helicobacter pylori infection: an overview.
AB  - For many decades the dictum 'no acid, no ulcer' dominated thinking on the
      pathogenesis of peptic ulcer. When I was a medical student, not surprisingly, the
      standard therapy for a peptic ulcer was an antacid possibly combined with
      carbenoxolone. As a medical registrar, I was involved in the early studies with
      H2-receptor antagonists which, at the time, many of us believed would lead to the
      removal of peptic ulceration as a clinically important disease. It was soon
      evident, however, that ulcers returned rapidly when the H2-receptor antagonist
      was withdrawn and the concept of maintenance therapy was born. Within about 5
      years of the launch of the first H2-receptor antagonist, cimetidine, two major
      developments occurred namely the discovery of Helicobacter pylori and the
      characterisation of the proton pump with the development of drugs to inhibit its
      action. The discovery of H. pylori not only turned the aetiopathogenesis of
      peptic ulceration on its head but soon emerged as a major factor in the causation
      of gastric cancer and mucosa associated lymphocytic tissue (MALT) gastric
      lymphoma. The potential clinical impact of this organism continues to expand,
      with suggestions that it might be involved in growth retardation in children and
      possibly a factor in the development of ischaemic heart disease. The high
      prevalence of this organism worldwide presents clinicians and other healthcare
      workers with a formidable challenge with regard to its control at a population
      level.

PMID- 9604426
TI  - Helicobacter biology--discovery.
AB  - The presence of gastric spirochaetal organisms was first documented over a
      century ago. Though repeatedly reported in the medical literature, it was felt
      that these spiral bacteria were merely contaminants and the reports were
      generally ignored by the medical community. On 22 October 1982, at a meeting of
      the Royal Australian College of Physicians, successful culture of these
      'Campylobacterlike organisms' from gastric biopsy specimens was reported for the
      first time. Moreover, it was shown that their presence was associated with
      gastritis and, possibly, with peptic ulceration. The subsequent discovery of the
      pivotal role of Helicobacter pylori in a wide range of conditions has
      revolutionised our understanding of gastroduodenal diseases. Improvements in
      diagnostic and therapeutic options, combined with the gradual acceptance of the
      aetiological role of an infective agent in peptic disease, have led to a
      remarkable change in the management of gastroduodenal conditions in the past
      decade.

PMID- 9604427
TI  - Helicobacter--species classification and identification.
AB  - The genus Helicobacter was created in 1989 with H. pylori as the type species.
      Since then the genus has expanded to include about 18 species. Some species were
      reclassified from Campylobacter, but most were newly discovered microorganisms
      from gastric or intestinal sites in mammalian host animals. The essential
      property of almost all helicobacters is the presence of sheathed flagella. Most
      species possess strong ureolytic ability, particularly those associated with
      gastric mucosa, and exhibit considerable diversity in cell morphology with
      respect to cell length, number and location of flagella, and presence of
      periplasmic fibrils. H. pylori has a global distribution and infects human
      gastric mucosa exclusively but there is some evidence for infection in cats.
      Genomes of isolates from different individuals are unusual in their diversity in
      gene order and sequences within individual genes. 'H. heilmannii' is another
      gastric spiral shaped organism less frequently infecting humans but commonly
      found in cat and dog gastric tissue. H. felis is important in the mouse model of
      infection. A range of conventional phenotypic tests as well as some new PCR based
      assays are available for identifying isolates of Helicobacter from clinical
      specimens.

PMID- 9604428
TI  - Helicobacter pylori--molecular genetics and diagnostic typing.
AB  - The genome of H. pylori is 1.68-1.73 Mb in size and contains a relatively low GC
      content (an average of 32.5 mol%). Physical and genetic maps of five H. pylori
      strains (NCTC 11637, NCTC 11638, NCTC 11639, UA 802 and UA 861) have been
      constructed and the complete genome sequence of strain 26695 has been determined.
      At least 50 genes, some of which play important roles in the physiology and
      pathogenicity of the bacterium, have been cloned. Marked genomic sequence
      variability has evolved from stain to strain demonstrated by random arrangement
      of 17 known genes on the chromosome and frequent mutations within individual
      genes. Based on such variability, sensitive and efficient molecular tying
      techniques such ribotyping, AR-PCR, PCR-RFLP, PCR-DNA sequencing and PFGE-RFLP
      have been developed and widely applied in both epidemiological and clinical
      studies of this pathogen. Subtypes of vacA (encoding a vacuolating cytotoxin) and
      the intermediate forms of a pathogenicity island (the cag region) have been
      identified in different H. pylori strains and these individual vacA subtypes are
      associated with specific clinical manifestations of H. pylori infection. Further
      studies on relationships between the genetic diversity and pathogenicity of H.
      pylori strains would lead to the development of novel and efficient therapeutic
      strategies for eradication of this microorganism.

PMID- 9604429
TI  - Epidemiology of Helicobacter pylori: acquisition, transmission, population
      prevalence and disease-to-infection ratio.
AB  - This article focuses on factors relating to acquiring Helicobacter pylori,
      including re-acquiring H. pylori infection after successfully treatment. It
      considers variables that increase the risk of infection and explores the chances
      that an infected individual will develop symptomatic disease.

PMID- 9604430
TI  - Clinical science of Helicobacter pylori infection: ulcers and NSAIDs.
AB  - It is now clear that Helicobacter pylori is a major aetiological factor in peptic
      ulcer disease. About 95% of patients with duodenal ulcers and perhaps 80% of
      patients with gastric ulcers are infected with this bacterium and its eradication
      greatly diminishes recurrence of these ulcers. Many patients are still not
      receiving the benefit of this treatment, however. Most patients who have peptic
      ulcers without H. pylori infection are taking non-steroidal anti-inflammatory
      drugs (NSAIDs), although this may not be recognised or admitted. Such patients
      have to be managed by withdrawal of these agents or by giving protective agents
      such as misoprostol. If H. pylori is present in a patient who develops an ulcer
      whilst taking NSAIDs, it remains unclear whether it is beneficial to eradicate
      the infection, but this seems advisable in case the ulcer is due to the infection
      in that particular patient.

PMID- 9604431
TI  - Helicobacter pylori infection and non-ulcer dyspepsia.
AB  - Epidemiological, pathophysiological and therapeutic studies have been carried out
      in order to try and establish whether an association between H. pylori infection
      and non-ulcer dyspepsia exists. A meta-analysis of pooled data showed that the
      prevalence of H. pylori infection in dyspepsia was higher than in controls (odds
      ratio 2.3), but this may be explained by selection bias. No convincing symptom
      profiles have been found to be associated with the infection, and there have been
      no consistent observations regarding the effects of the infection on
      gastroduodenal motility or sensation. Clinical trials in adults have been
      equivocal. Although a recent meta-analysis identified an overall benefit of H.
      pylori therapy, only selected trials could be included. Some studies have
      suggested that significant symptom improvement requires up to 12 months follow-up
      to be documentable. Little relevant paediatric clinical trial data are available.
      While it is possible that H. pylori may be responsible for symptoms in a small
      proportion of patients with non-ulcer dyspepsia and in some of these cases anti
      H. pylori therapy may be beneficial, this remains to be established.

PMID- 9604432
TI  - Helicobacter pylori infection and cancer.
AB  - This paper will briefly review the evidence for the role of Helicobacter pylori
      infection in the aetiology of gastric cancer and consider the implications of
      this relationship. The critical issue of whether H. pylori eradication may play a
      part in a strategy for the prevention of gastric cancer will then be discussed.
      Although this paper will largely be concerned with epidemiological evidence, it
      should be emphasised that an understanding of the mechanistic basis to the H.
      pylori-cancer relationship is also advancing rapidly and this area will be
      reviewed in the paper by Correa elsewhere in this issue.

PMID- 9604433
TI  - Helicobacter pylori infection and gastric lymphoma.
AB  - Gastric lymphoma of mucosa associated lymphoid tissue (MALT) has characteristic
      clinicopathological features that are different from nodal-type B cell lymphomas.
      Before a lymphoma can arise within the stomach, MALT has to be acquired as part
      of a response to an immunological stimulus. In most instances, gastric MALT is
      acquired in response to infection by Helicobacter pylori. There are several
      features of MALT lymphoma, such as plasma cell differentiation and follicular
      colonisation, that suggest that these lymphomas, although demonstrated on the
      basis of clonality studies to be neoplastic, retain some immunological drive. In
      vitro studies have shown that co-culturing cells derived from low grade MALT
      lymphomas with H. pylori results in tumour cell proliferation in a T cell
      dependant manner. Clinical studies have taken this discovery further and shown
      that patients with early low grade gastric MALT lymphoma treated with anti
      Helicobacter therapy can show regression of their tumours. It is now generally
      accepted that eradication of H. pylori is a central component of the management
      of MALT lymphoma.

PMID- 9604434
TI  - Non-gastrointestinal consequences of Helicobacter pylori infection.
AB  - Evidence relating H. pylori to non-gastrointestinal disease is sparse and
      inconclusive. Suggested mechanisms whereby infection might increase
      cardiovascular risk include release of acute-phase reactants including
      fibrinogen, reduction of HDL cholesterol, elevation of homocysteine levels and
      immunological cross-reactivity between bacterial and human heat shock proteins.
      Six published studies relating H. pylori seropositivity to various measures of
      ischaemic heart disease (IHD)-angiography, acute myocardial infarction, angina
      symptoms, or electro-cardiographic abnormalities-are all consistent with a modest
      (up to 2-fold) elevation in risk of IHD among infected subjects after adjustment
      for age, socioeconomic status and conventional cardiovascular risk factors. The
      pooled odds ratio from 1 longitudinal, 3 case-control and 2 cross-sectional
      studies is 1.4 (95% confidence interval 1.1-1.8). Further large-scale
      longitudinal studies are required to quantify the predictive value of
      seropositivity, to clarify the causal interpretation and to assess the underlying
      mechanisms for any link between H. pylori infection and ischaemic heart disease.

PMID- 9604435
TI  - Clinical significance of Helicobacter infection in children.
AB  - Helicobacter pylori infection of the gastric mucosa causes chronic gastritis and
      is associated with peptic ulcer disease and gastric carcinoma. These are
      conditions which usually occur in adult life. However, H. pylori is an infection
      which is mainly acquired in childhood. The overall prevalence of H. pylori in
      children is 10% in developed countries but can be as high as 30-40% in children
      from lower socio-economic groups. In developing countries, the prevalence of H.
      pylori in children ranges from 80-100%. H. pylori gastritis does not appear to be
      associated with symptoms in children in the absence of duodenal ulcer disease. H.
      pylori infection is present in the vast majority of children with duodenal ulcer
      disease and, as in adults, eradication of the organism results in long-term
      healing of duodenal ulceration. H. pylori infection acquired in childhood is now
      considered to be a significant risk factor for the development of gastric
      carcinoma. The World Health Organization has classified H. pylori as a Group 1
      carcinogen. Specific epidemiological questions which need to be answered in
      children include the age at which infection is acquired, specific risk factors
      for infection, the mode of transmission and the risk of reinfection following
      treatment. Recently, a one week treatment regimen using colloidal bismuth
      subcitrate, metronidazole and clarithromycin has been shown to be effective in
      treating children, but compliance is important. Currently there are no guidelines
      on the need to treat children and a consensus is urgently required on this issue.

PMID- 9604436
TI  - H. pylori virulence factors.
AB  - Among people infected with Helicobacter pylori, the virulence of the infecting
      strain is a major determinant of who develops disease. Strains producing
      vacuolating cytotoxin activity are more commonly isolated from people with peptic
      ulcers than without. The gene encoding the toxin, vacA, varies between strains,
      especially in its signal sequence and mid regions. vacA genotype influences
      cytotoxin activity, and signal sequence type correlates closely with peptic
      ulceration. Infection with strains possessing cagA (cytotoxin associated gene A)
      is more common among people with peptic ulceration or gastric adenocarcinoma than
      without. cagA is a marker for the cag pathogenicity island, which includes genes
      necessary for the enhanced inflammation induced by pathogenic strains.
      Serological detection of infection with cagA+ strains is at present the best
      practical test for virulence. However, before a strategy of screening and
      selective treatment can be considered, it is important to assess whether cagA-
      strains are entirely non-pathogenic.

PMID- 9604437
TI  - Interactions between H. pylori infection, gastric acid secretion and anti
      secretory therapy.
AB  - There is evidence of a two-way interaction between gastric acid secretion and H.
      pylori-associated gastritis. Gastric acid secretion influences the density of H.
      pylori colonisation, its distribution within the stomach and the severity of the
      mucosal inflammatory response to the infection. In addition, H. pylori gastritis
      alters gastric acid secretion. In subjects with a predominant antral gastritis,
      it increases acid secretion predisposing to duodenal ulcer, whereas in others
      with predominant body gastritis, acid secretion is impaired and the subjects have
      an increased risk of gastric cancer. The two-way interaction between acid
      secretion and H. pylori gastritis is observed when H. pylori-positive subjects
      are treated with proton pump inhibitor agents. The inhibition of acid secretion
      induces a body gastritis and this inflammation of the body mucosa inhibits acid
      secretion thus augmenting the anti-secretory effect of the drug. In this article,
      we discuss the interaction between gastric acid secretion and H. pylori gastritis
      and its importance in determining disease outcome.

PMID- 9604439
TI  - Carcinogenesis, apoptosis and cell proliferation.
AB  - Biological agents, especially viruses, have been linked to the carcinogenesis
      process in major human cancers, especially lymphomas (retroviruses),
      hepatocarcinomas (hepatitis viruses) and carcinomas of the female genital organs
      (papilloma viruses). Chronic infection and inflammation have long been suspected
      to play a role in human carcinogenesis. Helicobacter pylori is the first
      bacterial infection recognized as a human carcinogen, essentially on the basis of
      epidemiological evidence of causality. Contrary to most other recognized human
      carcinogens, experimental evidence of carcinogenesis is lacking. As a
      consequence, mechanistic explanations of H. pylori carcinogenesis at this point
      in time are hypothetical.

PMID- 9604438
TI  - Helicobacter pylori and gastric inflammation.
AB  - H. pylori infection leads to gastric inflammation, characterised histologically
      by surface epithelial degeneration and infiltration of the gastric mucosa by
      acute and chronic inflammatory cells. H. pylori adherence, the production of a
      vacuolating cytotoxin and bacterial enzymes all contribute to epithelial damage.
      Recruitment and activation of immune cells in the underlying mucosa involves H.
      pylori chemotaxins, epithelial-derived chemotactic peptides (chemokines) such as
      IL-8 and GRO-alpha, and pro-inflammatory cytokines liberated by mononuclear
      phagocytes (TNF alpha, IL-1 and IL-6) as part of non-specific immunity. Antigen
      specific cellular immunity results in a predominant Th1 lymphocyte response with
      an increase in IFN-gamma secreting T-helper cells, whilst humoral responses lead
      to the production of anti-H. pylori antibodies and complement activation. The
      complex network of cytokines implicated in these inflammatory responses include
      counter-regulatory elements such as IL-10 which may serve to damp down
      inflammation. Molecular mimicry of host structures by H. pylori, with the
      generation of specific immunity directed against self-antigens may also
      contribute to host injury. Progress in molecular biology has revealed
      considerable genomic diversity amongst H. pylori strains, with cag+ bacteria
      being associated with increased chemokine and cytokine responses and more severe
      degrees of gastric inflammation. Strain hetereogeneity may contribute towards the
      wide spectrum of disease manifestations encountered in clinical practice.

PMID- 9604440
TI  - Animal models for host-pathogen interaction studies.
AB  - There is no model of Helicobacter pylori infection that exactly mimics the human
      diseases. In a particular, there are no good models of ulceration or gastric
      adenocarcinoma. Patterns of gastritis induced in the animals tend to be
      lymphocytic and lack the neutrophil infiltration typical of H. pylori infection
      in the adult. However, the animal models are starting to provide valuable
      information with respect to factors involved in the colonisation of the gastric
      mucosa and the importance of host factors in the development of gastric atrophy,
      as well as making possible the screening of potential therapeutic agents and
      vaccine candidates. Models include gnotobiotic piglets, primates, cats, dogs,
      ferrets and a range of rodents. Recent advances in the mouse models mean that
      they will allow us to dissect bacterial host interactions in a novel manner due
      to the availability of a wide range of immunological reagents and numerous mutant
      or transgenic strains.

PMID- 9604441
TI  - Microbiological and serological diagnostic tests for Helicobacter pylori: an
      overview.
AB  - Different invasive and non-invasive diagnostic tests are available for the
      diagnosis of H. pylori in the individual patient. In practice, endoscopic tests
      are best for a primary diagnosis of H. pylori infection because endoscopy allows
      assessment of treatment indications. The new rapid urease tests may help the
      clinician in treatment decision-making. Culture is currently not recommended for
      routine evaluation, but it is becoming increasingly important in certain
      populations with higher prevalence of drug resistance, since it allows testing
      for susceptibility to antibiotics. Serological testing has been recommended for
      initial pre-endoscopy or pre-treatment screening in dyspeptic patients. However,
      several current 'in-office' tests appear insufficiently accurate or would need
      further validation before being recommended for use in clinical management
      strategies at a primary care level. The urea breath tests are best suited to
      confirm eradication early after treatment, while laboratory serology tests are of
      limited use, since 6 months are required before a result can be obtained. The
      serological office tests cannot be used for post-treatment assessment of H.
      pylori status.

PMID- 9604442
TI  - Clinical practice--breath tests.
AB  - The underlying principle of the two non-invasive radio-labelled urea breath tests
      is similar. Both are positive when the patient's stomach is colonised by
      Helicobacter pylori because the organism's urease enzyme splits the orally
      administered urea isotope to labelled CO2 which is then detected in the expired
      breath. The tests thus reflect active infection and are ideally suited to
      monitoring the success or failure of different eradication therapies as well as
      studying rates of acquisition and re-infection/late recrudescence post treatment.
      [13C]-urea should always be used in children since it is the stable non
      radioactive isotope but the [14C]-urea breath test is suitable for most adults,
      since the dose of radioactivity is minimal.

PMID- 9604443
TI  - Current regimens for treatment of Helicobacter pylori infection.
AB  - The aim of treatment of Helicobacter pylori is eradication of the bacterium from
      the foregut. Treatment is difficult because of the bacterium's habitat and
      acquired resistance to commonly used antibiotics. Dual therapy, the 2 week
      combination of omeprazole or ranitidine bismuth citrate and either amoxycillin or
      clarithromycin, eradicates H. pylori in 50-80% of patients. Classical triple
      therapy is commonly associated with side effects, is highly dependent on
      patient's compliance, and is significantly less effective in the presence of
      metronidazole-resistant strains of H. pylori, where eradication may be 50%. One
      week, twice daily, proton pump inhibitor (PPI)-based triple therapy regimens
      eradicate about 90% of H. pylori and are associated with mild side effects.
      Second line regimens include 7 days treatment with omeprazole and 3 times daily
      amoxycillin and metronidazole or a PPI-based quadruple therapy regimen. In some
      cases, the bacterium defeats all attempts at eradication.

PMID- 9604444
TI  - Antibiotic resistance in Helicobacter pylori infection.
AB  - Resistance to antibiotics is considered as the primary reason for failure of
      eradication therapies. Resistance to clarithromycin is due to a decrease in
      binding to the ribosomes associated with a point mutation on the 23S rRNA. Its
      rate in Europe varies from 0-15%, with 5% in the UK. The resistance influences
      dramatically the success of the treatments. Resistance to metronidazole is due to
      a lack of reduction of this compound whose genetic basis is still unknown. The
      resistance rate in Europe varies from 10-50%, with 25% in the UK. It influences
      the success of treatments to a lesser extent than clarithromycin resistance. The
      initial eradication treatment can be prescribed without testing for
      susceptibility and must include a combination of two antibiotics, while stressing
      the importance of compliance to the patient. In case of failure, susceptibility
      testing must be performed. Few data are currently available on alternative
      therapeutic strategies when H. pylori is resistant to both clarithromycin and
      metronidazole.

PMID- 9604445
TI  - Clinical practice--strategies for management of dyspepsia.
AB  - If every person, particularly the young with dyspepsia, were initially tested for
      Helicobacter pylori and treated if positive and re-assured if negative, a
      substantial proportion of endoscopies could be saved, and it is difficult to
      conceive how this would add to the expense of managing dyspepsia if most H.
      pylori positive dyspeptics are going to receive treatment after endoscopy in any
      event. An algorithm for the management of dyspepsia is proposed.

PMID- 9604446
TI  - Vaccine development against infection with Helicobacter pylori.
AB  - Infection with Helicobacter pylori, is one of the most prevalent infections world
      wide, where approximately 50% of adults in the developed world and over 90% of
      inhabitants in the developing world are infected. Chronic infection with H.
      pylori is the cause of gastritis, peptic ulcer disease and is a risk factor for
      gastric adenocarcinoma. Recent studies have demonstrated the suitability of an
      immunization strategy in the prevention and treatment of H. pylori infection, and
      the potential for management of disease. Mucosal administration of purified
      recombinant sub-unit proteins of H. pylori, together with a mucosal adjuvant, has
      identified urease to be highly efficacious in prophylactic and therapeutic animal
      model studies, and show partial therapeutic activity in humans. Several other
      antigens are also effective, and the recent sequencing of the H. pylori genome
      has led to an intensive effort in antigen discovery. Other research has centered
      on the identification of novel approaches for delivery, and the immunological
      mechanisms underlying protective immunity. In this review, preclinical data and
      the results of early-stage clinical trials and directions for future research on
      Helicobacter vaccines are described.

PMID- 9604447
TI  - Is there a rationale for eradication of Helicobacter pylori? Cost-benefit: the
      case for.
AB  - Screening and treating the community for Helicobacter pylori would have seemed
      inconceivable 5 years ago. This has now become a real possibility given that H.
      pylori is a major risk factor for gastric carcinoma. Screening should not be
      introduced, however, before the costs and benefits of the programme are
      established. It has been estimated that 1:30-1:60 of the UK population die from
      an H. pylori related disease. If treating H. pylori were to reduce premature
      mortality, then this would be a persuasive argument for a screening strategy. The
      financial costs of screening and treating H. pylori are significant but this
      would be partially offset by savings that would accrue from reducing dyspepsia in
      the community. Indeed, decision analysis models suggest H. pylori screening is
      cost-effective. The potential benefits are enormous and prospective randomised
      trials are urgently required to establish whether such a programme is worthwhile.

PMID- 9604448
TI  - Helicobacter pylori eradication cost-benefit: the case against.
AB  - Helicobacter pylori is an important human pathogen, implicated in the
      pathogenesis of peptic ulcer disease, gastric cancer, and perhaps also in other
      non-gastrointestinal disease. There is little doubt that in peptic ulcer disease
      at least, there is a strong argument for its eradication on both clinical and
      economic terms. The majority of subjects infected with Helicobacter pylori never
      develop clinically overt disease, and it is this group that the clinical and
      financial benefit of eradication needs to be closely examined.

PMID- 9604449
TI  - The effects of UVB plus calcipotriol on systemic calcium homeostasis in patients
      with chronic plaque psoriasis.
AB  - We studied the effects of combining topical calcipotriol, used at the maximal
      licensed dose, and narrow-band short wave ultraviolet light (TL01) on systemic
      calcium homeostasis in the treatment of chronic plaque psoriasis. Patients were
      randomized in an open fashion to receive either UVB alone, UVB plus 100 g of
      calcipotriol (50 micrograms/g) ointment per week or calcipotriol ointment alone
      (100 g/week). With the exception of a slight increase in serum phosphate in the
      group receiving combination therapy (from 0.92 to 1.22 mmol/l; P = 0.046), no
      differences were observed between or within the groups. Psoriasis area and
      severity scores (PASI) improved to a greater extent in those patients receiving
      both UVB and calcipotriol (P = 0.045). The combination of UVB and calcipotriol is
      a safe, effective treatment for chronic plaque psoriasis.

PMID- 9604450
TI  - Cutaneous non-epidermotropic lymphoma associated with human immunodeficiency
      virus infection.
AB  - A case of pure non-epidermotropic cutaneous lymphoma in a human immunodeficiency
      virus-infected patient is reported following a viral opportunistic infection
      [cytomegalovirus (CMV) hepatitis]. The lymphoid infiltrate was Epstein-Barr virus
      and CMV negative with a CD30-positive T-cell phenotype. Molecular analysis
      demonstrated T cell receptor gene rearrangement, but a non-aggressive disease
      course was noted supporting a cautious therapeutic approach in this case.

PMID- 9604452
TI  - Neutrophilic dermatoses associated with myeloid malignancy.
AB  - The neutrophilic dermatoses are significantly associated with myeloid
      malignancies. We now describe the clinical and histological features of 11
      patients with these disorders, namely Sweet's syndrome in three cases, pyoderma
      gangrenosum in two, and neutrophilic eccrine hidradenitis in one; there were also
      five others which could not be categorised as recognised entities. Our
      observations, as well as those from a review of the literature, support the
      hypothesis that in the neutrophilic dermatoses associated with myeloid
      malignancy, a common mechanism may be involved.

PMID- 9604451
TI  - Lichen myxoedematosus associated with human immunodeficiency virus infection-
      report of two cases and review of the literature.
AB  - Lichen myxoedematosus (LM), or papular mucinosis, is an uncommon papular eruption
      caused by the dermal deposition of mucin. Three clinical forms can be
      distinguished, namely localised, disseminated (involving more than one site), and
      generalised LM, the last is called scleromyxoedema, and demonstrates erythema and
      skin sclerosis. Paraproteinaemia, often consisting of an abnormal IgG with lambda
      light chains, is usually present in patients with LM. Visceral involvement has
      also been documented. An association between LM and human immunodeficiency virus
      (HIV) infection has been reported recently. We now describe two further HIV
      positive patients with LM and present a review of the literature regarding this
      association.

PMID- 9604453
TI  - Cutaneous granulomatous vasculitis after herpes zoster infection showing
      polyarteritis nodosa-like features.
AB  - Various cutaneous lesions have been described after herpes zoster infection, such
      as lymphomas, pseudolymphoma and granulomatous conditions (granuloma annulare,
      tuberculoid granuloma, sarcoidosis). However, granulomatous vasculitis is an
      extremely rare sequel. We now describe a case of superficial granulomatous
      vasculitis with deep 'polyarteritis nodosa (PAN)-like' arteritis that developed
      after herpes zoster infection. Polymerase chain reaction did not detect genome of
      the herpes virus. We suggest that this condition could be an immune response to
      viral proteins.

PMID- 9604454
TI  - Subungual squamous cell carcinoma in Darier's disease.
AB  - We report the first case of subungual squamous cell carcinoma in a patient with
      Darier's disease (keratosis follicularis). The presence of human papillomavirus
      DNA was confirmed, consistent with its probable role in carcinogenesis at this
      site. The role of an altered immune state is discussed as an additional factor.
      Squamous cell carcinomas may be overlooked when they occur among the other
      cutaneous manifestations and complications of Darier's disease. A solitary,
      ulcerating nail bed lesion warrants biopsy to exclude squamous cell carcinoma.

PMID- 9604455
TI  - Disseminated superficial actinic porokeratosis occurring in two members of an
      Asian family.
AB  - Disseminated superficial actinic porokeratosis (DSAP) is a genodermatosis which
      usually affects fair-skinned individuals at sites of chronic sun exposure,
      although the face is usually spared. We now report the occurrence of this
      condition in a Pakistani mother and her 13-year-old daughter, both predominantly
      with facial lesions.

PMID- 9604456
TI  - Enlarging congenital haemangioma in an adult--a new entity?
AB  - We report the case of a 39-year-old woman with a persistent congenital vascular
      lesion, which unusually is continuing to enlarge. Histologically, the lesion is a
      thin-walled haemangioma with numerous mast cells. Currently, the precise
      mechanism of vessel proliferation in such lesions is unknown, but it is important
      in the pathogenesis of both haemangiomas and other dermatological conditions, as
      well as in wound healing and the formation of tumour metastases. We discuss
      various angiogenic factors with particular reference to the putative role of the
      mast cell in the pathogenesis of haemangiomas.

PMID- 9604457
TI  - Thymoma-associated cutaneous graft-versus-host-like reaction.
AB  - A 47-year-old man presented with diarrhoea, acquired hypogammaglobulinaemia and a
      cutaneous graft-versus-host-like reaction in association with a spindle cell
      thymoma. Graft-versus-host reactions usually occur following allogeneic
      transplantation or transfusion of immunocompetent lymphoid cells but have been
      described rarely in the context of a thymoma.

PMID- 9604458
TI  - Acquired perforating dermatosis and diabetic nephropathy--a case report and
      review of the literature.
AB  - A case of acquired perforating dermatosis associated with diabetic nephropathy is
      described. The case is unusual in that the dermatosis first developed
      approximately 1 year after renal transplantation rather than at a time when renal
      function was more severely impaired or during haemodialysis. There was a partial
      response to treatment with isotretinoin but the use of this drug was limited by
      the development of hyperlipidaemia. The relevant literature is reviewed.

PMID- 9604459
TI  - Hypomelanosis of Ito with unusual associations.
AB  - Hypomelanosis of Ito (HOI) is a neurocutaneous disorder which clinically is a
      well-characterised disease, in which chromosomal instability may be a component.
      Various neurological and other non-cutaneous malformations have been reported in
      association with the characteristic swirling pattern of hypopigmentation. We
      report two cases of this rare condition, one with hitherto unreported
      associations.

PMID- 9604460
TI  - Thalidomide-induced toxic pustuloderma.
AB  - We report a case of toxic pustuloderma secondary to thalidomide in a patient with
      severe nodular prurigo. To our knowledge this is the first reported case. With
      the increasing use of thalidomide for a variety of dermatological conditions it
      is clearly important that this rare side-effect now be recognised.

PMID- 9604461
TI  - PUVA photocarcinogenesis in Cheshire.

PMID- 9604462
TI  - Gianotti-Crosti syndrome as a presenting sign of EBV-induced acute infectious
      mononucleosis.

PMID- 9604463
TI  - Prolonged remission of urticaria pigmentosa following topical steroid therapy
      under hydrocolloid occlusion.

PMID- 9604464
TI  - A case of urticarial drug eruption from loxoprofen sodium.

PMID- 9604465
TI  - Occupational lung diseases and global occupational health on the Net.
AB  - Occupational lung disease is a major area of concern in occupational health,
      exhibiting a diverse panorama across countries. While pneumoconiosis is deemed to
      be the most common occupational disease in many developing countries, emphasis is
      shifting towards asbestos-related lung diseases and occupational asthma in
      industrialized countries. Following the Occupational Health for All strategies
      set forth by the World Health Organization, we propose that a model system based
      upon the Global Health Network can serve as an effective vehicle towards the
      prevention of occupational lung diseases on a global scale. It has the potential
      to: (1) enhance transmission of data and collaboration with the primary health
      care system in disease surveillance; (2) strengthen research and information
      transfer and (3) promote education and training at all levels of prevention, with
      a possible application to the interpretation of chest radiograms.

PMID- 9604466
TI  - A five-year study comparing early retirements on medical grounds in ambulance
      personnel with those in other groups of health service staff. Part I: Incidences
      of retirements.
AB  - The objective of this study was to compare morbidity between ambulance staff and
      other groups of health service workers, to facilitate planning of occupational
      health (OH) services. A retrospective study of employees of The Eastern Health
      and Social Services Board, Northern Ireland was conducted. Subjects were 181 men
      and 353 women assessed at OH between 1988-92 and found eligible (on the basis of
      permanent incapacity) to apply for early retirement on medical grounds (EROMG).
      Ambulance personnel showed a high rate of EROMG (55.9/1,000 per annum) both
      compared with previous ambulance studies (5.7-22.5/1,000), and with other groups
      in the present study (manual 24.8/1,000, nursing 5.9/1,000 and non-manual
      2.6/1,000). Indirect standardization was used to correct for age-sex differences
      between groups, by deriving standardized early retirement ratios (SERR).
      Ambulance and manual staff showed high SERRs (636, CI = 558-714 and 164, CI = 149
      179), whereas nursing and non-manual staff showed low SERRs (91, CI = 75-107 and
      38, CI = 25-52), (all results except that for nursing staff being significant at
      p < 0.001). There is evidence that ambulance staff are a group with high
      morbidity, and thus deserving of particular attention in terms of preventative
      and health promotional activities. Other issues requiring consideration in
      relation to ambulance staff are redeployment and lowering of the retirement age.

PMID- 9604467
TI  - Employers' awareness and compliance with occupational health and safety
      regulations in Taiwan.
AB  - An investigation of employers' awareness and compliance with occupational health
      and safety (OHS) regulations was conducted in a representative group of employers
      randomly selected from the manufacturing industry in Taiwan. A total of 1,003
      employers were interviewed by trained public health personnel. Ten questions
      related to perceptions of general OHS and five practices on OHS regulations were
      measured. The results of this study show that the employers were better aware of
      their responsibility for posting safety warnings, personal protection and
      providing safety and health equipment. They were less aware of their
      responsibility in minimizing injuries and accidents in the workplace and in not
      hiring someone who was found unfit for a certain job from pre-employment physical
      examination. Less than half of employers knew about regulations of environmental
      monitoring and even fewer had heard of Material Safety Data Sheets. Level of
      education and size of the plant were highly associated with employers' awareness
      of OHS and the awareness was the most significant predictor in the five practices
      of OHS regulations in this study. Promotion of employers' awareness of OHS in
      small sized industries in particular, is warranted to enhance better compliance,
      and a focus for these efforts is identified by this investigation.

PMID- 9604468
TI  - The prevalence of work-related upper limb disorders in a printing factory.
AB  - The association between problems of the upper limb and the workplace is complex.
      A large printing manufacturer in the North West of England sought the advice of
      both a surgeon, specializing in problems of the upper limb and an ergonomist in
      an attempt to control the frequency of these abnormalities amongst its workforce.
      The prevalence of these problems prior to and after the introduction of a number
      of recommendations was collated and the results are discussed. Effectively the
      introduction of sensible and sympathetic modifications to the workplace appeared
      to reduce the number of upper limb disorders.

PMID- 9604469
TI  - Biomarkers, screening and ethics.
AB  - Rapid scientific advances, such as those in biomarker technology, have made a
      significant impact on the ethics and practice of occupational health. Biomarkers
      are extensively used in occupational health practice. In the pre-employment
      stage, preventive or predictive testing can be performed. Preventive testing aims
      to avert accidents that may occur if a medically unfit worker undertakes a job
      that he is unable to perform. For safety sensitive jobs, routine testing of a
      worker's functional capacity in the actual job would suffice in most cases.
      However, a recently quotes application of a test is the screening for mutations
      of the cardiac myosin-heavy chain and troponin genes among asymptomatic persons
      with a family history of sudden death from hypertrophic obstructive
      cardiomyopathy. Predictive testing hopes to forecast the risk of a worker
      developing an illness. The aims may vary. One aim may be to exclude a susceptible
      worker from working in a hazardous environment. Another aim may be to avoid
      employment of a worker who is likely to develop an illness which could lead to
      higher employer health care costs. A pertinent question to consider is whether
      the test undertaken is to benefit the individual or to fulfil some administrative
      or financial need. Among exposed workers, screening may be conducted for
      biomarkers of exposure or effect. As the aim is to prevent the onset of clinical
      illness, the physician must take responsibility for initiating requests for
      screening. The appropriate response to the effect of technical and societal
      advances on ethics is the updating of ethical guidelines by the profession.
      However, in the context of unvalidated biomarkers being used for screening, it
      may be necessary to require a regulatory body to ensure that the tests are
      accurate and effective, and that they are not used to discriminate against
      individuals.

PMID- 9604470
TI  - Job strain and cardiovascular risk factors among members of the Danish
      parliament.
AB  - Sudden cardiovascular events among well-known politicians attract much attention-
      from the mass media and from the public. No previous studies have assessed the
      job strain profile and level of known cardiovascular risk factors among
      parliamentary politicians. The study was carried out within the frameworks of the
      Copenhagen City Heart Study. Some 102 members of the Danish parliament (70 men
      and 32 women) agreed to participate, giving a response rate of 55%. Three sex-
      and age-matched participants were drawn for each politician from the Copenhagen
      City Heart Study. In addition to the completion of large questionnaires on health
      and working conditions, all participants had a thorough examination, including
      measurements of height and weight and blood pressure and the drawing of a venous
      blood sample for the determination of serum lipids, ApolipoproteinA1 and
      ApolipoproteinB and fibrinogen. Job strain factors and established cardiovascular
      risk factors were the main outcome factors. Politicians reported much higher job
      demands, but also much more influence on their job than others. Politicians
      smoked less, consumed more wine, had higher levels of ApolipoproteinA1, and were
      taller. With respect to other major cardiovascular risk factors, serum lipids,
      blood pressure and physical activity, there was no difference between politicians
      and controls. Politicians had greater job demands, but also more control over
      their job than others, indicating that the job strain phenomenon should not
      increase their risk of cardiovascular disease. Other cardiovascular risk factors,
      job related or conventional, which were unevenly distributed between politicians
      and controls all favoured politicians. In conclusion, politicians had a more
      beneficial cardiovascular risk factor profile than a matched random sample from a
      comparable background population.

PMID- 9604471
TI  - Assess workers' needs and preferences first before planning a physical fitness
      programme: findings from a polytechnic institute in Singapore.
AB  - Workplace physical fitness programmes are usually poorly attended because the
      activities do not meet workers' needs. We investigated leisure-time physical
      activity and its relation to sociodemographic characteristics and cardiovascular
      risk factors in a polytechnic institute in Singapore before planning a physical
      fitness programme. Low leisure-time physical activity (defined as no activity or
      engaging in physical activity less than once per week) was more prevalent among
      older women, married workers, smokers and men with unhealthy dietary habits. The
      type of physical activity varied with age and gender, with a preference for
      walking by women and older men and jogging by younger men. Low physical activity
      was significantly associated with sickness absence and self-reported stress in
      women and higher values of triglycerides and low density lipoprotein cholesterol
      in men. This survey helps to identify target groups for physical fitness
      programmes and determine leisure-time physical activities specific to workers'
      preferences by age and gender.

PMID- 9604472
TI  - Life-style related health promotion needs in oil refinery employees.
AB  - This report describes the screening procedure used in the assessment of health
      promotion needs in a group of oil refinery employees (n = 885). The aim of the
      study was to assess the life-style related health promotion needs before
      initiating an intervention programme study. The frequency of different health
      promotion needs and their distribution according to age, gender and employee
      group were examined, as well as the factors explaining different health promotion
      needs. The assessment was based on laboratory tests and questionnaires covering
      the target areas of physical activity and fitness, dietary habits, overweight,
      blood pressure, serum lipids, smoking, alcohol consumption, sleep, mental health,
      and musculoskeletal symptoms. Life-style related health promotion needs were
      frequent. Self-assessed health was strongly associated with health promotion
      needs in most of the ten target areas and also with the total number per person
      of areas with health promotion needs. Health promotion needs were also associated
      with such demographic variables as age, gender, basic education, and vocational
      training. If health promotion activities are provided to employees in a company,
      assessment of individual needs is necessary to find the employees with the
      greatest need of health promotion actions. This study presents one method of
      screening, although certain simplification is needed to make it fit into the
      daily routines. The contents of health promotion activities could also vary
      according to the differences related to age and gender observed in health
      promotion needs of the target population.

PMID- 9604473
TI  - The renewed mission of the occupational physician: to be or not to be a doctor?

PMID- 9604474
TI  - A cluster of haematuria cases in a pesticide-manufacturing plant.
AB  - In a pesticide manufacturing and formulating facility, 10 employees out of 48
      were shown to have haematuria on dipstick testing. They included seven of the 27
      production workers, all of whom had worked in both of two particular areas prior
      to the commencement of the routine urine testing. Five of the seven production
      workers with haematuria underwent further investigations, and in all five the
      haematuria was glomerular in origin. Two underwent renal biopsy, which showed
      irregular attenuation of the glomerular basement membrane (GBM) but no
      abnormality by light microscopy. Immunofluorescence studies were negative. This
      case series of glomerular haematuria is not readily explained by chance, false
      positive dipstick testing, or a recognizable non-occupational cause. Thin GBM
      disease, which is a benign condition, appears the likely explanation. Thin GBM
      disease is usually an autosomal dominant condition, but clustering of these
      genotypes in this small population is improbable.

PMID- 9604475
TI  - Reality checks, CME and the pursuit of professionalism.

PMID- 9604476
TI  - Needlestick injuries among female veterinarians: frequency, syringe contents and
      side-effects.
AB  - In a mixed-mode survey of all 1970-80 female graduates of all US veterinary
      colleges, information was obtained regarding several health, personal and
      occupational factors including data on occupational needlestick events. Among the
      2,532 survey respondents, 1,620 reported one or more needlesticks after
      graduation from veterinary college (64.0% of all respondents). A total of 2,663
      stick events were reported, although the descriptions of each puncture event
      varied in quality/completeness, probably due in large part to their retrospective
      nature. Substances most often injected include vaccines, antibiotics,
      anaesthetics and animal blood. Of the 438 sticks resulting in at least one side
      effect (16.4% of all sticks), 337 were classified as mild and localized at the
      site of injection (12.4% of all sticks, approximately 77% of sticks producing a
      side-effect), with 18 characterized as severe and systemic (0.7% of all sticks,
      approximately 4% of sticks producing a side-effect). One accidental self
      injection of a prostaglandin compound resulted in a spontaneous abortion,
      heightening awareness that occupational needlesticks may also represent a serious
      human reproductive health hazard. The estimated overall needlestick injury rate
      for this group of health care professionals was 9.3 sticks per 100 person-years
      (PYs) of practice, comparable to reported rates among health care workers such as
      nurses, laboratory technicians and hospital housekeeping staff. Accounting for
      underreporting of the stick events, the actual injury rate is likely to be at
      least 20 sticks per 100 PYs. When stick rates were estimated by clinical practice
      type (small animal, large animal and mixed practice), all-small-animal and mixed
      practice veterinarians demonstrated the highest rates, with all-large-animal
      practitioners demonstrating a rate lower by about 40%.

PMID- 9604477
TI  - Mixed-mode survey of female veterinarians yields high response rate.
AB  - In a recent study of female veterinarians, a subgroup of health professionals
      growing rapidly in number, the authors employed a mixed-mode survey design in
      targeting the cohort of women graduating from all US veterinary colleges during
      the 11-year period 1970-80 (n = 2,997). The questionnaire elicited information on
      a variety of health and occupational factors and required 35 minutes on average
      to complete. In the first stage, a modified version of Dillman's Total Design
      Method for mailed, self-administered questionnaires was employed, yielding a
      response rate of 82.9%. In the second stage, a telephone interview of all mail
      non-respondents was attempted, yielding a response rate here of only 30.1%, but
      increasing the overall response rate among those contacted to 90.2%. Non
      respondents differed little from mail (early) or telephone (late) respondents
      with respect to year of graduation and geographic region of veterinary college
      attendance. Gentle probing of telephone non-respondents suggested the personal
      nature of some questions and the amount of time required to answer all questions
      were the main reasons they chose not to participate. It therefore appears that
      conventional survey techniques may be successfully employed in health studies of
      health professionals, particularly if issues of great concern to the target
      population are addressed.

PMID- 9604478
TI  - Improving mental well-being in the workplace.
AB  - Occupational physicians, who are in a key position to influence company policy on
      mental health, have limited access to education on mental health. This paper
      discusses the results of a postal survey of occupational physicians that was
      designed to identify the mental health information needs of occupational
      physicians, determine the way in which this information should be disseminated
      and measure the extent to which occupational physicians encounter mental health
      problems in the workplace.

PMID- 9604479
TI  - Survey of occupational health problems in an operational military environment.
AB  - 16 Armoured Field Ambulance provided primary and secondary medical care to
      British troops in Bosnia from April to October 1996. Patients presenting at both
      levels were reviewed and categorized into occupational illness, non-occupational
      disease and non-occupational injury. The results show that occupational illness
      was a small but significant component of primary care (8%) with non-occupational
      injury accounting for < 1%. In secondary care, the more serious nature of the
      occupational disease seen is shown in that it accounted for 38% of all admissions
      and 44% of the 149 patients who had to be evacuated from theatre for further
      treatment. Non-occupational injury represented 8% of admissions and 13% of
      evacuations.

PMID- 9604480
TI  - Enzyme exposure, smoking and lung function in employees in the detergent industry
      over 20 years. Medical Subcommittee of the UK Soap and Detergent Industry
      Association.
AB  - This study was undertaken to examine the long term relationship between lung
      function, smoking and exposure to enzymes in the detergent industry. A total of
      731 male workers from five locations in the United Kingdom were subject to
      respiratory health surveillance including lung function testing over a period of
      4-20 years. Exposure groups were defined by job history. Significantly different
      rates of fall in FEV1 and FVC with time were found by geographical location and
      by smoking habit, but there were no consistent trends with enzyme exposure.

PMID- 9604481
TI  - Musculoskeletal complaints in lock assemblers, testers and inspectors.
AB  - The objectives of this study were to determine the prevalence of musculoskeletal
      complaints in a population of lock assemblers in the West Midlands; to follow one
      group over 12 months and to explore the relationship between survey data,
      sickness absence information and claims experience. An adapted Nordic
      Musculoskeletal Questionnaire was used to determine annual and weekly prevalence
      and annual disability rates for musculoskeletal complaints. There was no
      statistically significant difference in complaints between the six companies,
      apart from an increased reporting of neck (p < 0.001), upper back (p < 0.001) and
      hip (p < 0.05) symptoms at one company (Site 4) during the week prior to the
      study. When the study was repeated at Site 4 one year later, new employees had
      significantly fewer complaints of neck and elbow discomfort over the previous
      year and week, but no difference in wrist complaints was reported. This survey of
      lock assemblers has highlighted high levels of self-reported upper limb
      complaints when compared to other referent groups of workers.

PMID- 9604482
TI  - Exploring the need for an occupational health service for those working in
      primary care.
AB  - A research nurse interviewed 55 practice staff in 11 general practices to
      ascertain their views about their needs for occupational health care. In a second
      parallel study, a specialist in occupational medicine undertook an in-depth audit
      of occupational health provision in five other general practices with respect to
      the organization, the health and safety process, the services and the working
      environment. In the first study, the majority of practice staff reported the need
      for various aspects of occupational health care, particularly stress at work. In
      the second study, general practitioners and practice managers possessed a basic
      awareness of occupational health matters such as Health and Safety legislation,
      but their limited knowledge was not translated into effective management. General
      practice staff did not know where to obtain occupational health advice; most
      practices had no policies or procedures in place to manage health and safety.
      Both studies illustrate the need for expert occupational health advice in primary
      care.

PMID- 9604483
TI  - Respiratory disease in workers exposed to colophony solder flux fumes: continuing
      health concerns.
AB  - The objectives of this study were to establish the prevalence of respiratory,
      eye, nose and throat symptoms of likely work-relation in workers exposed to
      colophony solder flux fumes and to assess their lung function. A cross-sectional
      study was conducted in four medium-sized electronics firms in which control
      measures to capture solder flux fume were absent or visibly ineffective. All
      female solders and women working adjacent to soldering stations completed an
      administered questionnaire concerning symptoms, work history and current
      soldering frequency. Measurements were made of their forced vital capacity (FVC)
      and forced expiratory volume in one second (FEV1) during the course of a working
      shift, using a Vitallograph-Compact portable spirometer. Using weekly hours of
      soldering as a crude index of current exposure, workers were classified into high
      (> or = 37 h/wk) and low (< or = 20 h/wk) exposure groups, and their health
      responses were compared in the analysis. Individuals with symptoms suggestive of
      work-related asthma were also asked to provide serial peak flow measurements over
      a further 2-week period, and adequate returns were charted and read by two
      physicians experienced in the diagnosis of occupational asthma. Data were
      collected on 152 female workers (overall participation rate = 97%). Symptoms of
      recurrent, persistent wheeze and/or chest tightness were reported by 75 (49%) of
      interviewees; 36 (24%) gave a history typical of occupational asthma and six more
      (4%) a history of pre-existing asthma worsened at work. Twenty-one (14%) of the
      workforce complained of recurrent breathlessness on moderate exertion; 41 workers
      (27%) had work-related symptoms of the nose or throat and 25 (16%) had work
      related eye symptoms. The odds ratios for 'all wheeze', shortness of breath, and
      work-related eye, nose and chest symptoms were all significantly greater (raised
      about 4-5 fold) in women who soldered > or = 37 h/wk when compared with those
      soldering < or = 20 h/wk. After adjustment by logistic regression for atopy, age
      and smoking status even higher risk estimates were generally obtained. The odds
      ratios (OR) and 95% confidence intervals (CI) for high vs. low were: for 'all
      wheeze', OR = 7.2, CI = 2.5-20.7; for work-related eye symptoms, OR = 5.2, CI =
      1.4-19.8; for work-related nasal symptoms, OR = 4.0, CI = 1.4-11.1 and for
      occupational asthma symptoms, OR = 5.2, CI = 1.4-14.2. Mean FEV1 and FVC
      percentage difference from expected were slightly lower in full-time solderers
      than in part-time solderers, but the differences were not significant. Thirty
      seven of the 51 workers (73%) who were asked to carry out serial peak flow
      measurements completed an adequate return: 27 of these records confirmed the
      presence of asthma, and in all of the cases the history suggested onset post
      dating employment in soldering. Eleven peak flow records were indicative of
      occupational asthma. The health problems associated with colophony solder flux
      were documented over 18 years ago, but are still clearly apparent in situations
      where adequate control has not been achieved.

PMID- 9604484
TI  - Interpretation of the trace metal analysis profile for patients occupationally
      exposed to metals.
AB  - Trace element profile analysis detects and quantifies the presence of several
      metals simultaneously at low concentrations in the body. In occupational
      medicine, it may be used to monitor exposure or to evaluate suspected toxicity.
      Clinical interpretation is often difficult because, with the exception of lead
      and possibly cadmium, there is little firm information on toxicity thresholds.
      For these tests, the reference ranges typically reflect low levels of exposure in
      the general population and it is expected that workers handling metals in
      occupations such as welding and industries such as steelmaking will have higher
      levels. Interpretation requires some knowledge of the toxicokinetics of the metal
      of interest and the preferred medium for analysis for each: serum, whole blood or
      urine (preferably 24-hour collection). Trends are often more informative than
      concentrations at one time. Trace element values are reported together with a
      reference range which must be distinguished from the normal range of other
      clinical tests. As a practical matter, the greatest interpretation problems tend
      to be found with manganese because serum levels have a poor correlation with both
      recent exposure and neurological symptoms. Molybdenum and vanadium are often
      found to be elevated among workers exposed to metals who show no evidence of
      clinical illness. Interpretation of the trace element profile analysis overall
      when an elevation occurs generally requires close attention to the pattern of
      elevation, clinical context, absolute and relative magnitude of the elevation and
      knowledge of the exposure history.

PMID- 9604485
TI  - Concomitant alveolitis and asthma following exposure to triphenylmethane
      triisocyanate.
AB  - A 36-year-old man was admitted to hospital with increasing breathlessness. He had
      been exposed to triphenylmethane triisocyanate. Pulmonary function tests
      demonstrated physiological abnormalities consistent with both asthma and
      alveolitis. Exposure to less common isocyanates may not be immediately apparent.
      Asthma developing after isocyanate exposure is well recognized. Pneumonitis is a
      relatively rare complication. Measurement of gas transfer may be helpful in the
      investigation of isocyanate toxicity.

PMID- 9604486
TI  - Morbidity, mortality and the media.

PMID- 9604487
TI  - Bioequivalence study of two capsule formulations of omeprazole.
AB  - Bioequivalency of Omeraz, a test-product of Arab Pharmaceutical Manufacturing
      Company (Jordan) and Losec, a reference product by Astra (Sweden), was evaluated
      by a randomised crossover study on 22 healthy male volunteers. Serum
      concentrations of omeprazole were measured by an HPLC assay. There were no
      statistically significant differences between the two products in terms of serum
      profile and pharmacokinetic parameters including AUC, Cmax, Tlag, Tmax, MRT, Ke
      and T1/2. The AUC ratios (Omeraz/Losec) for 24 hours and for infinity were
      respectively 1.02 with a 90% C.L. of 0.88-1.16 and 1.00 with a 90% C.L. of 0.88
      1.14. The two products may be considered as bioequivalent in terms of the extent
      of absorption as indicated by the AUC ratios. However, the confidence limits of
      Cmax fall outside the FDA accepted range.

PMID- 9604488
TI  - [Usage modeling test in aerosols formulations].
AB  - Authors emphasize the importance of "usage-modelling" test concerning the
      uniformity of doses in the case of aerosol formulations, containing propellants
      or supplied with atomising devices. Weight measurement was carried out to
      identify the uniformity of doses per actuation keeping non-use periods in the
      case of water-based solutions with different density and suspension containing
      HFC propellants. It can be concluded that uniformity of doses--applying non-use
      periods during the testing time--significantly depends on the composition, the
      density of the formulation and the spraying mechanism of the atomising device.

PMID- 9604489
TI  - [Effect of imidazole antifungal agents on colony formation by murine bone marrow
      CFUc (colony forming units in culture].
AB  - In spite of modern antifungal therapy, the prognosis of systemic mycoses in
      neutropenic patients is usually poor without recovery of neutrophil counts. So,
      even a minor myelotoxicity might be a significant disadvantage of any drug used
      for the treatment of neutropenic patients with fungal infections. Since "Colony
      Forming Units in culture" (CFUc), the common progenitors of granulocytes and
      macrophages, are supposed to be a major target of agents damaging bone marrow, we
      studied the inhibitory effect of four imidazole antifungal drugs to colony
      formation by murine CFUc in vitro. Clotrimazole, econazole, miconazole or
      ketoconazole were added to soft agar bone marrow cell cultures at final
      concentrations of 1 to 30 mg/l at the beginning of the 7 day culture period. A
      dose-dependent inhibitory effect on colony formation by CFUc was observed with
      all imidazole drugs studied. The 50 percent inhibitory concentrations (IC50s)
      were 3.54 mg/l for clotrimazole, 8.07 mg/l for econazole, 14.04 mg/l for
      miconazole, and 16.11 mg/l for ketoconazole. Human pharmacokinetic data available
      in the literature on these drugs may help to assess the potential in vivo
      relevance of our results. The serum levels of clotrimazole and econazole, even
      after oral administration, remain lower than those found to inhibit colony
      formation by murine bone marrow in our experiments. Taking into consideration
      that clotrimazole and econazole are used only topically in the clinical practice,
      our data do not suggest any clinically significant suppression of bone marrow by
      these two drugs. Intravenous administration of high doses of miconazole, however,
      may result in serum concentrations approaching the IC50 for colony formation by
      murine bone marrow cells in vitro. As for ketoconazole, it may suppress the
      proliferation of murine bone marrow progenitor cells in vitro at concentrations
      produced in vivo by high doses (12.5-18 and 30-50 mg/l after 400 or 600 mg,
      respectively). The serum levels produced by a daily dose of 200 mg ketoconazole
      (about 4 mg/l), however, did not reduce significantly the number of colonies in
      murine bone marrow cultures. Our present results warrant further studies of the
      myelotoxicity of miconazole and ketoconazole in vivo in mice with neutropenia
      induced by cytostatic agents.

PMID- 9604490
TI  - [Determination of the end-point of naproxen sodium granules in Glatt VG-WS-CD
      high-shear granulator fluid bed dryer equipment].
AB  - Determination of the end-point of granulation in the Glatt VG-600-WS-CD-120 high
      shear granulator-fluid dryer is presented. The method of the determination based
      on measuring of the impeller motor current during the granulation operation. The
      influencing parameters during the granulation of naproxen-sodium on granule
      quality are also shown. Reproductibility of the acceptable granule-quality in
      serial producing is documented.

PMID- 9604491
TI  - Study of local anaesthetics. Part 139. Preformulation study of N-[2-(2
      heptyloxyphenylcarbamoyloxy)-ethyl] dimethylammonium chloride.
AB  - In the course of the drug form development of substance XIX B (N-[2-(2
      heptyloxyphenylcarbamoyloxy)-ethyl] dimethylammonium chloride [1]) the influence
      of auxiliary substance, namely glycerol (GL), propylene glycol (PG) and sorbitol
      (SO), used in the form of 5, 10, 15 and 20% solution, on the surface tension,
      partition coefficient, viscosity and liberation from aqueous solutions was
      studied. These parameters can influence the bioavailability. The obtained results
      show that as an optimal additive 5% SO may be used since this ensured maximal
      amount of liberated substance XIX B.

PMID- 9604492
TI  - [Effects of drugs on re-excitability of synapses of isolated frog ganglia].
AB  - Effects of different pharmacons on the non-excitable period (NEP) and on the
      relative excitable period (REP) was studied in the sympathetic ganglionic
      synapses of the frog (Rana esculenta). Using paired stimulation we demonstrated
      that hexamethonium, magnesium, pempidine, tetraethylammonium (TEA) and d
      tubocurarine chlorides significantly prolonged both NEP and REP at ganglion
      blocking threshold concentrations. Their maximum effect occurred within 30-60 min
      after the start of the exposition. Hemicholine and neostigmine prolonged only NEP
      but not REP while lidocaine influenced neither period applying continuous
      repeated stimulation at low frequencies (0.1-12.5 Hz). TEA showed no effect,
      however, at higher frequencies (14.3-20.0 Hz) it exerted a frequency-dependent
      depressant effect on the amplitude of the compound action potential.

PMID- 9604493
TI  - Private versus NHS?

PMID- 9604495
TI  - Independent and private dentistry.

PMID- 9604494
TI  - The British Association for the Study of Community Dentistry.

PMID- 9604496
TI  - Links between dental and general health.

PMID- 9604497
TI  - Links between dental and general health.

PMID- 9604498
TI  - Working towards a reduction in absenteeism.

PMID- 9604499
TI  - Funding for secondary care.

PMID- 9604500
TI  - Success of OCSE examinations.

PMID- 9604501
TI  - Success of OCSE examinations.

PMID- 9604502
TI  - GDS funding and NHS dentistry.

PMID- 9604503
TI  - An unusual case of hyperdontia [corrected].
AB  - The presence of supernumerary teeth is not uncommon but there have been very few
      documented cases of bilateral maxillary and mandibular supernumeraries distal to
      third molars. This case study looks at the frequency of and complications arising
      from supernumeraries as well as specifically covering the presentation and
      subsequent removal in practice of five supernumeraries distal to third molars.
      Good and thorough radiographs are essential for correct diagnosis.

PMID- 9604504
TI  - Advances in periodontal diagnosis. 8. Commercial diagnostic kits based on GCF
      proteolytic and hydrolytic enzyme levels.
AB  - Biomarkers of periodontal disease activity may be obtained from potential
      proteolytic and hydrolytic enzymes of inflammatory cell origin. Commercial
      diagnostic tests and those under development are discussed along with their
      advantages and disadvantages.

PMID- 9604505
TI  - Unexplained physical symptoms in dental patients.
AB  - Physical symptoms for which there is no adequate organic pathology may be
      psychological in origin. The concept of somatisation described in this paper may
      be helpful in understanding these unexplained symptoms. Two case histories
      describe unusual physical symptoms that occurred following dental treatment and
      the role of somatisation in their development.

PMID- 9604506
TI  - Substantial variation in the provision of sedation for primary dental care.

PMID- 9604507
TI  - Dental caries is concentrated in the first permanent molars.

PMID- 9604508
TI  - The perception of dental diseases prior to the advent of modern dentistry needs
      re-appraisal.

PMID- 9604509
TI  - Sedation in primary dental care: an investigation in two districts of northern
      England.
AB  - OBJECTIVE: To determine the current provision of sedation in primary dental care
      and investigate the knowledge and attitudes of dental practitioners and others on
      the use of sedation. DESIGN: Qualitative interviews and postal questionnaire
      survey. SETTING: Health districts of Bradford (West Yorkshire) and South Durham,
      UK in 1996. SUBJECTS AND MATERIALS: 15 key individuals associated with NHS
      primary dental services were interviewed. Questionnaires were sent to all 260 NHS
      general dental practitioners and community dental service clinicians. RESULTS:
      208 questionnaires (80%) were returned. 42% of respondents reported current
      sedation use, with oral administration the favoured technique (26%). Significant
      differences were found between districts for intravenous sedation use (7%
      Bradford, 41% South Durham, P < 0.001). Almost all participants agreed the value
      of sedation in dental care for adults and children, for nervous, phobic patients
      or in association with unpleasant forms of treatment and 45% of dentists felt
      that provision should be expanded. Training, availability of referral services,
      finance and patient demand were seen as encouraging factors. CONCLUSIONS:
      Substantial variations in sedation provision between the two districts were
      associated with teaching at the nearest dental schools. Innovative use of
      resources could help the expansion of provision supported in this study.

PMID- 9604510
TI  - Dental caries in 12-year-old children and the effectiveness of dental services in
      Salford, UK in 1960, 1988 and 1997.
AB  - OBJECTIVE: To investigate the dental health of 12-year-old children and the
      effectiveness of dental services in 1997 and compare the results with studies
      carried out in 1960 and 1988. BASIC RESEARCH DESIGN: Analytical survey using a
      one in five random sample of children in all seven secondary schools in Salford
      UK. Standard clinical criteria were used. SETTING: Clinical examinations were
      carried out in school. PARTICIPANTS: 65 boys and 49 girls were examined. OUTCOME
      MEASURES: Caries experience expressed as DMFT, Restorative Index and Care Index.
      RESULTS: The boys and girls both had a mean DMFT of 1.65. (95% confidence
      intervals were 1.18-2.12 for the boys and 1.16-2.14 for the girls.) This compared
      with means of 2.34 (1.85-2.83) for boys and 3.40 (2.63-4.17) for girls in 1988,
      and 6.04 (5.65-6.43) and 6.54 (6.09-7.00), respectively in 1960. The prevalence
      of caries fell least in first permanent molar teeth. The Care Index for the boys
      was 22.0 in 1960, 51.4 in 1988 and 31.5 in 1997. The pattern was similar for the
      girls for whom the values were 19.5, 48.6 and 32.2 respectively. The boys'
      Restorative Index scores (modified to include fissure sealants) were 25.7 in
      1960, 58.5 in 1988 and 57.1 in 1997. The girls' scores were 23.9, 53.7 and 58.0.
      CONCLUSIONS: Caries has declined considerably in Salford since 1960. More of the
      total disease was concentrated in first permanent molar teeth in 1997. Indices,
      which measure the effectiveness of dental services, show that a greater
      proportion of overall disease was being treated in 1988 than in 1960 or 1997.

PMID- 9604511
TI  - Dental pain and suffering prior to the advent of modern dentistry.
AB  - In Prehistoric and Mediaeval times few dentitions in this country remained intact
      much after the age of 40-45 years. The point is made that dental caries and
      periodontal disease played little part in this early disintegration and it is
      unlikely that the population of this time suffered severely with their teeth. A
      change in dietary habits in the late seventeenth and early eighteenth century
      measurably increased the lifespan of the dentition, but also radically altered
      the prevalence of caries. This change is likely to have been responsible for a
      vast increase in dentally-related pain and suffering which was only capable of
      being tackled as a social problem by the advent of modern dentistry.

PMID- 9604512
TI  - A survey examining the attitudes of general dental practitioners toward change in
      undergraduate dental education.
AB  - AIM: To determine the attitudes of general dental practitioners toward aspects of
      change in undergraduate dental education. DESIGN: Descriptive postal survey using
      a cross-sectional random sample of general dental practitioners administered in
      1997. SUBJECTS: 689 general dental practitioners practising in five regions of
      England with close proximity to a dental school selected by a one in two
      stratified random sample. RESULTS: Response rate: 70%. The questionnaire was both
      valid and reliable with an internal consistency reliability coefficient of 0.84.
      Responses identified strong support for preparing dental students for the wider
      role of the dentist and an emphasis toward self-directed learning. Other themes
      emerging from the investigation included support for learning to work as part of
      a dental team and for students to have experience of general dental practice
      early on in the undergraduate course. CONCLUSIONS: These responses have
      implications for curriculum design, syllabus, teaching methods, resources and
      staff development for dental schools in the UK.

PMID- 9604513
TI  - Web site of the month.

PMID- 9604514
TI  - An attachment theory approach to treatment of the difficult patient.
AB  - This article reviews the role of attachment in difficult-to-treat patients. It is
      suggested that difficulty often arises in the treatment of these patients because
      of their inadequate understanding of mental functioning in themselves and in
      others. The capacity to mentalize is seen as a function of early attachment
      relationships. Vulnerability introduced by insecure attachment is frequently
      compounded by a history of intense trauma, leading these patients to defensively
      inhibit their capacity to think about mental states in their abusers, which then
      generalizes to other attachment relationships. The clinical implications of this
      model are discussed.

PMID- 9604515
TI  - Complex cognitive therapy treatment for personality disorder patients.
AB  - Preliminary studies have found cognitive therapy to be a promising treatment for
      personality disorder patients. Therapy is based on an individualized formulation
      of the case and is generally much more complex and potentially more lengthy than
      the treatment for patients with Axis I disorders alone. Modifications of
      treatment include a greater focus on the therapeutic relationship, increased
      emphasis on developmental events, variations in session structure, and
      utilization of specialized strategies to alter dysfunctional beliefs and
      compensatory behavioral strategies.

PMID- 9604516
TI  - Algorithms for pharmacological treatment of personality dimensions: symptom
      specific treatments for cognitive-perceptual, affective, and impulsive-behavioral
      dysregulation.
AB  - A pharmacological approach to treating patients with personality disorders (PD)
      is based on evidence that some dimensions of personality are mediated by
      variations in neurotransmitter physiology and are responsive to medication
      effects. Target symptoms for pharmacotherapy in the PD patient are derived from
      expressions of cognitive-perceptual, affective, and impulsive-behavioral
      dysregulation of central neurotransmitter functions. Pharmacotherapy is directed
      at state symptoms during periods of acute decompensation and at trait
      vulnerabilities, which represent the diathesis to future episodes. A basic
      assumption of this approach is that neurotransmitter biology transcends Axis I
      and Axis II definitions and that closely related symptoms may share a common
      pathophysiology, independent of categorical definition. A common pathophysiology
      implies the possibility of shared responsiveness to medication. Using a
      dimensional definition of symptom domains, the author has developed treatment
      algorithms for cognitive-perceptual symptoms, affective dysregulation, and
      impulsive-behavioral dyscontrol in personality disorder patients.

PMID- 9604517
TI  - Outcome research on the psychosocial treatment of personality disorders.
AB  - This brief overview of outcome research on psychosocial treatment of personality
      disorders first examines difficulties in using existing classifications of
      abnormal personality. A summary is offered of uncontrolled investigations of the
      treatment of personality disorders, a few controlled studies, and literature on
      the impact of comorbid personality disorder on treatment of Axis I
      symptomatology. The conclusions take into account the particular challenges of
      these disorders in the current health care context.

PMID- 9604518
TI  - Addiction: a new paradigm.
AB  - The older view of addiction was that people became addicted because they were
      ignorant of the risks of addiction, they were unhappy, or they lacked healthy
      opportunities. Once addicted, they were hooked by physical dependence, causing
      them to continue use despite wanting to quit. The new paradigm of addiction
      focuses on reward and the powerful experience of falling in love with the feeling
      that addictive behaviors produce. Potential addicts seek brain reward and are
      heedless of the risks, of which they are seldom ignorant. Withdrawal is largely
      irrelevant. The problem of addiction is the power of brain reward. The new view
      of addiction has important implications for prevention, treatment, public policy,
      and medical treatment with controlled substances.

PMID- 9604519
TI  - Evolution of wraparound services at The Menninger Clinic.
AB  - The authors focus on the development of a wraparound program at The Menninger
      Clinic. This program explores alternatives to long-term hospitalization and
      residential treatment and provides comprehensive community-based services. After
      describing the history and evolution of this program, the authors highlight its
      current components (i.e., diagnostic understanding; assessment of the client's
      and family's strengths; identification of helpful functions of hospital or
      residential placement; crisis planning; family-centered community team; flexible
      funding; criteria for evaluating the plan's success). Each of these components
      contributes to a process that provides a high level of individualized treatment
      outside a hospital or residential setting. This process has provided a format for
      collaborating with families, community providers, schools, and managed care
      companies. It also integrates an understanding of developmental psychopathology
      with solution-focused, pragmatic approaches to behavior change.

PMID- 9604520
TI  - Transactions of the Topeka Psychoanalytic Society.

PMID- 9604521
TI  - An outbreak of viral gastroenteritis on board a cruise liner.

PMID- 9604522
TI  - House of Lords inquiry into antimicrobial resistance.

PMID- 9604523
TI  - Acute flaccid paralysis and the eradication of poliomyelitis.

PMID- 9604525
TI  - Intussusception.

PMID- 9604524
TI  - AIDS and HIV infection in the United Kingdom: monthly report.

PMID- 9604526
TI  - Pattern of intussusception at Gondar, Ethiopia.
AB  - Thirty three intussusception cases operated at the Gondar College of Medical
      Sciences hospital are presented. Thirteen of them were infants and the rest older
      children and adults. Clinical presentation, preoperative management, type of
      intussusception, cause, surgical procedures, and outcome are analysed.

PMID- 9604527
TI  - Comparative study of psychiatric morbidity among workers at a paint factory in
      Nigeria.
AB  - Inspite of numerous reports on the neurobehavioural effects of paints, there have
      been no such studies from Nigeria, where there are now many paint factories. The
      general aim of this study was, to assess the prevalence of specific psychiatric
      morbidity among workers in a large paint manufacturing factory. Using the
      Psychiatric Assessment Schedule (PAS), 60 workers (mean age, 38.1) directly
      involved in paint manufacture, 60 administrative staff (mean age 41.1) in the
      factory, and 60 postal workers (mean age 37.7) were assessed. Although higher
      proportions of factory workers (80%), and postal workers (73.3%) had positive PAS
      scores compared with administrators (36.7%), there were no significant
      differences in mean PAS scores across the groups. Two subjects each of factory
      workers (agoraphobia and dysthymia) and postal workers (dysthymia and generalised
      anxiety) fulfilled DSM-IIIR criteria for specific diagnosis. However, the paint
      workers had a wider spread of PAS symptoms, were significantly more likely to
      experience the symptoms constituting neurasthenia, had many more psychological
      complaints, experienced a wider variety of spontaneously reported symptoms, and
      constituted the most frequent users of health services. They had no knowledge of
      the possible mental health effects of exposure to paint. This level of distress
      is comparable to many reported findings.

PMID- 9604528
TI  - Malaria prevalence and use of self-protection measures against mosquitoes in Suba
      District, Kenya.
AB  - Malaria prevalence and status among other diseases were assessed in Suba
      District, Kenya, using data from past parasitological surveys and hospital
      records of clinically-diagnosed cases. A short prospective survey was also
      carried out to determine the methods people used for self protection against
      mosquito bites. Malaria was the leading cause of morbidity, constituting 42-48%
      of all illnesses clinically diagnosed at two health centres over a two-year
      period. Other common endemic diseases included infections of the upper
      respiratory and urinary tracts. The highest monthly number of malaria cases were
      recorded in July of each year. Malaria parasite rates in blood samples from
      people examined at 14 screening centres ranged from 24.4% to 99% over a distance
      of about 25 kilometres. The most popular method of self-protection against
      mosquitoes was mosquito nets followed by mosquito (pyrethrum-based) coils. Other
      methods included insecticidal sprays and smoke from plants traditionally
      associated with mosquito repellence.

PMID- 9604529
TI  - Prevalence of intestinal parasites in Kenyans with dyspepsia.
AB  - Dyspepsia and intestinal worm infestation are both common clinical conditions in
      a developing country like Kenya and thus this study was designed to look at the
      correlation between the two in a referral gastroenterology clinic at Kenyatta
      National Hospital. One hundred and twenty five patients with dyspepsia had their
      stool, duodenal aspirate and duodenal biopsy analysed for evidence of intestinal
      parasites. Seven (5.6%) were found to have various types of intestinal parasites
      with giardia lamblia comprising 42.8% of worms isolated. 71.4% of patients with
      dyspepsia and worm infestation had their symptoms improved after deworming, but
      the low prevalence of intestinal parasite in dyspeptic patients makes routine
      deworming not cost effective. Stool examination had the best yield for intestinal
      parasites.

PMID- 9604530
TI  - Prevalence of psychiatric morbidity among convicted inmates in a Nigerian prison
      community.
AB  - Studies of psychiatric morbidity in Nigerian prisons have not involved assessment
      for specific psychiatric disorders. The general aim of this study was to
      highlight the prevalence of psychiatric morbidity among convicted inmates at a
      medium security prison in Nigeria. In a one month period in 1996, 100 inmates
      (93% males, mean age, 31.4 years) of the prison in Benin City, were assessed,
      using the General Health Questionnaire (GHQ-30) and the Psychiatric Assessment
      Schedule (PAS). The 34 subjects who scored upto GHQ-30 cut-off, four, had
      specific axis I DSM III-R diagnoses, including, schizophrenia in two, major
      depression in two in recurrent mild depression in twenty one, generalised anxiety
      disorder in eight and somatisation disorder in one. On axis II, six subjects had
      antisocial personality disorder while another subject had probable mild mental
      retardation. On Axis III, 15 subjects had chronic physical illnesses, including
      one with epilepsy. Twenty five inmates had past histories of drug abuse prior to
      imprisonment, including cannabis (11%) and alcohol (13%). Total PAS scores were
      significantly predicted only by GHQ scores and length of stay in prison. There
      was no association between offence committed and psychiatric morbidity. Most
      subjects with psychiatric morbidity developed these illnesses while in prison.
      The findings differed from the situation in developed countries where personality
      disorders and substance use are much more prevalent. The fairly high level of
      psychiatric disorders underscores the need to improve medical services in the
      prison.

PMID- 9604531
TI  - Role of a general surgeon in obstetrics and gynaecology in a rural setting.
AB  - In a rural hospital in northern Nigeria, general surgeons performed 217 obstetric
      and gynaecologic operations over a five-year period. These operations were
      responsible for 23% of all operations at the hospital. Emergency operations were
      most frequent with caesarean section accounting for 90%. Eighty five per cent of
      the caesarean sections were performed for cephalopelvic dysproportion. The
      complications encountered were mostly septic complications, predominantly in
      patients who had caesarean section for obstructed labour. The overall mortality
      was 5.1% and neonatal mortality from caesarean section was 4.8%. It is concluded
      that in the abscence of an obstetrician and gynaecologist general surgery
      experience is required to manage obstetric and gynaecologic problems in rural
      areas. Such experience should be considered when recruiting doctors for rural
      hospitals in developing countries.

PMID- 9604532
TI  - Urinary tract stone disease in Nairobi.
AB  - At the Kenyatta National Hospital (KNH) and other private hospitals in Nairobi
      urinary stone disease is not being correctly diagnosed. Over a 15 year period
      (1980-1995) only 56 patients have been confirmed to have urinary tract stones out
      of the expected number of 220 patients. The age range was 10-60 years. The peak
      age was 30-40 years. Pain and haematuria were the commonest presenting symptoms.
      Ultrasonography and plane abdominal radiology were the commonest methods of
      diagnosis. Open surgery and endoscopic stone removal were the commonest modes of
      management. Extracorporeal shortwave lithotripsy (ESWL) has recently been
      introduced into the Nairobi Hospital, but was not functional at the time of this
      study. Percutaneous nephrolithotomy (PCNL) is possible but has not been
      adequately used due to lack of correct equipment. Septicaemia and haemorrhage
      were the commonest complications of the open surgery.

PMID- 9604533
TI  - Anthropometric profile of a black population of the Cape Peninsula in South
      Africa.
AB  - This study describes the anthropometry of an urban black population living in the
      Cape Peninsula, South Africa. A random sample of 986 selected adults aged 15-64
      years and 163 children aged three to six years, included data on heights,
      weights, and mid-upper arm circumferences and calculation of the body mass index
      (BMI). The mean height of men was 168.3 cm and that of women 158.3 cm. Mean
      weight, BMI and mid-upper arm circumference for men were 66.2 kg, 23.4 and 28.1
      cm and for women 69.8 kg, 27.8 and 30.6 cm respectively. The prevalence of
      underweight in men (BMI < 20) was 19% and in women (BMI < 19) 3.7%; 22% of the
      men were overweight (BMI > or = 25) and 7.9% obese (BMI > or = 30), while 36.4%
      of women were overweight (BMI > or = 24) and 34.4% obese (BMI > or = 30). More
      than half of the women above the age of 35 years were obese. Anthropometry of the
      three to six year old children was calculated for stunting, wasting and
      underweight, expressed in terms of the National Centre for Health Statistics
      standards, and revealed co-existing evidence of growth retardation and wasting
      with emergent obesity. These findings suggest that a part of this community, who
      may have been nutritionally deprived during childhood, has moved from
      undernutrition to extreme overnutrition without having achieved optimal
      nutritional status. Complexities that need to be considered when planning
      strategies to address malnutrition in the black South African population are
      identified.

PMID- 9604534
TI  - Socio-demographic characteristics of family planning clients and their possible
      influence on contraception in Malawi.
AB  - In a survey of family planning clients at the central Teaching Hospital,
      Blantyre, between July 1 and December 31, 1993, to determine their social,
      biological and reproductive profiles, contraceptive awareness and previous use,
      766 new clients were recruited and interviewed by means of partially structured
      questionnaire. Their mean age was 27 years, with a range of 15-43 years.
      Adolescents formed 10.1% and those above 35 years of age were 17.1%. 91.3% were
      married. While 12.6% had no formal education, 29.7% had secondary school
      education and higher. Their mean parity and living children were 3.6 and 3.1
      respectively. The mean desired fertility was 4.5. 93.3% of all clients had live
      births in their last pregnancies. Contraceptive awareness was quite high, about
      98.0%. However, only 30.9% had ever-used contraceptives before then. When these
      are looked at against a background of the corresponding situations in the
      country, it appears that the individuals seeking, accepting and using
      contraceptives in Malawi, are better off in the various aspects of life, thus
      suggesting their possible influence on contraceptive use. There is need to review
      the national family planning programme, address the contraceptive needs of
      adolescents and women aged above 35 years, improve formal female education,
      change the prevailing socio-cultural and traditional beliefs and practices which
      affect women adversely, thus empowering them over affairs of their health.

PMID- 9604535
TI  - Relationship between exposure to tobacco smoke and bronchial asthma in children:
      a review.
AB  - Asthma is a common chronic childhood disease yet not much is known about factors
      that determine its outcome. Cigarette smoke has been associated with lung cancer
      in adults but its effects on children has hitherto been underestimated and not
      well studied. Cigarette smoke has been noted through various research studies to
      influence the development and or the exacerbation of asthma in childhood.
      Furthermore the prevalence of childhood asthma is higher among the children of
      smoking parents, more so when both parents are smokers as compared to those of
      non-smoking parents. Corroborative evidence indicates elevated urine cotinine
      levels amongst children of smoking parents than those of non-smoking parents.
      There is a corresponding increase in prevalence and exacerbation of asthma
      symptoms among children with raised urine cotinine levels than those with low
      levels. The presence of other risk factors increases the risk of development and
      exacerbation of bronchial asthma in children exposed to tobacco smoke than those
      not exposed. Cigarette smoking is on the increase, especially in developing
      countries due to aggressive advertising and exportation by the tobacco industry
      from developed countries. International legislation is needed to regulate the
      production and exportation of tobacco products. However, this may be resisted by
      the influential tobacco industry and may not get the support from the developing
      countries due to economic gains from the sale of tobacco products. This scenario
      poses major health problems for the developing countries in the future.

PMID- 9604536
TI  - Primary malignant melanoma of the anorectum: case report.
AB  - A thirty year old Nigerian female presented with a large and advanced anorectal
      malignant melanoma. She had been treated for over eighteen months at a rural
      hospital for a mistaken diagnosis of haemorrhoids. The patient died before any
      form of treatment could be carried out. The rarity of this disease in the black
      Africa is highlighted and the characteristics of the disease briefly reviewed.
      The importance of digital and protoscopic rectal examination in patients bleeding
      per rectum is emphasised.

PMID- 9604537
TI  - Transient focal neurological deficits in patients with hypoglycaemia and
      hyperglycaemia: report of four cases.
AB  - A case of hypoglycaemia and three cases of hyperglycaemia presenting with focal
      neurological deficits are presented. The focal presentations were hemiparesis and
      focal convulsion that returned to normal upon correction of the blood sugar.
      Elderly patients not uncommonly present with transient focal neurologic deficits
      related to abnormalities in blood sugar levels. In these patients correction of
      blood sugar levels per se may ameliorate symptoms and signs making it unnecessary
      to investigate for cerebrovascular disease. In diabetic patients on insulin or
      oral hypoglycaemic agents focal neurologic deficit should alert the clinician on
      the possibility of hypoglycaemia.

PMID- 9604538
TI  - Kleine-Levin syndrome: case report.
AB  - A case of Kleine-Levin syndrome in a fourteen year old junior high school female
      student is described. The episodic disorder was characterised by excessive sleep,
      voracious appetite, irritability, confusion and electro-encephalographic changes.
      Remission was spontaneous. Prospects for organic aetiology, differential
      diagnosis, and the importance of early detection are discussed.

PMID- 9604540
TI  - Routine antibiotics for snake bite.

PMID- 9604539
TI  - Amoebic liver abscess in pregnancy: report of two cases.
AB  - Amoebic liver abscess is a rare complication of pregnancy. It however, carries
      significant morbidity and because the diagnosis is often delayed, physicians in
      developing countries need to be reminded of its possibility when patients present
      with right lower chest and abdominal pain. This study presents the clinical
      reports of two cases in which the diagnosis was delayed and review the literature
      on amoebic liver abscess in pregnancy.

PMID- 9604541
TI  - Haemolysin production by environmental isolates of Vibrio parahaemolyticus from
      Andamans.
AB  - Sixty marine water samples were collected from various coastal sites around Port
      Blair at different times during August 1996 to July 1997. The specimens were
      subjected to standard procedure for isolation and identification of V.
      parahaemolyticus. Forty four V. parahaemolyticus isolates were detected from
      these specimens and all showed clear haemolysis on Wagatsuma agar plates. The
      haemolytic activity was abolished by heating the culture supernatants at 60
      degrees C for 10 min and enhanced when plates were kept at 4 degrees C. When
      isolates were subjected to PCR assay for tdh gene, only one showed the presence
      of the gene. The results indicate the existence of pathogenic V. parahaemolyticus
      in the marine environment of these islands.

PMID- 9604542
TI  - HLA antigen profile in pulmonary tuberculosis patients & their spouses.
AB  - HLA-A, -B, -DR and -DQ antigen profile was studied in pulmonary tuberculosis
      patients (n = 209) and their spouses (family contacts; n = 50) and healthy
      volunteers (n = 72). An increased frequency of HLA-A-10, B7, B15, DR2 and DQ1 was
      seen in the pulmonary-TB (PTB) patients when compared to the total control
      subjects (n = 122). However, a significant increase was seen only with HLA-DR2 (P
      < 0.001; Pc < 0.01; Relative Risk 2.3) and -DQ1 (P < 0.005; Pc < 0.015; Relative
      Risk 2.8). Among the spouses and the corresponding patients, a similar increase
      of HLA-DR2 was seen. A decreased frequency of HLA-A19, B8, B17, B35, DR5 and DR6
      were seen in PTB as compared to control groups. The present study suggested that
      HLA-DR2 and DQ1 genes/gene products may be associated with the susceptibility to
      tuberculosis either alone or in combination with other HLA or non-HLA genes.

PMID- 9604544
TI  - Proteinase activity & virulence of Entamoeba histolytica on passage through
      hamster liver.
AB  - This study was undertaken to determine the enzymatic differences in the process
      of increasing the degree of virulence in E. histolytica successively passaged in
      hamster liver. Substrate gel electrophoresis was used to compare proteinase
      banding patterns under reducing conditions from whole cell lysates of one axenic
      E. histolytica (strain HM1:IMSS) and five xenic isolates of the same strain of E.
      histolytica passaged five times through hamster liver. Trophozoites successively
      passaged in hamster liver showed in supernatants, major bands in the 56-97 kDa
      region whereas only the axenic strain produced additional band at 34 KDa.
      Inoculation of amoebic trophozoites into hamster led to progressive increase in
      proteinase activity of supernatants as well as increased virulence of amoebae;
      proteinase activity of amoebae showed an excellent correlation with their
      virulence. All the infected animals died when activity of proteinase was 0.152 mg
      of protein.

PMID- 9604543
TI  - Projection of HIV infection in Calcutta.
AB  - Starting with the base year of 1991, the HIV infection projection for 1992-99 for
      the total, as well as various high-risk sub-populations of Calcutta, the first of
      its kind is provided. These projections are based on statistical methodology
      developed in this paper. Our methodology for spread of HIV infection takes into
      account various social interactions and practices and also uses available data.
      Rates of these interactions and practices and estimates of demographic parameters
      used in making projections were obtained primarily from surveys and census data.
      Since one of these estimated rates, that of HIV transmission rate through
      heterosexual encounters between an infected and an uninfected had a large range,
      we have provided two sets of projections based on the largest of these rates
      (worst-case scenario) and another that is consistent with the available data. The
      total projection of the number of HIV infected cases in Calcutta for 1999 is
      between 49,000 and 1,26,000. Separate projections are also provided for high-risk
      sub-groups. Among these, the sex workers expectedly will continue to manifest the
      highest numbers of newly infected cases. The temporal rate of increase in
      prevalence is projected to be alarmingly higher in the general population than
      even among sex workers, although the actual prevalence will continue to be the
      lowest in the general population compared to all other sub-groups of the
      population.

PMID- 9604545
TI  - The influence of alpha-thalassaemia on the haematological & clinical expression
      of sickle cell disease in western India.
AB  - We evaluated the clinical and haematological features of 29 sickle cell anaemia
      patients with associated alpha-thalassaemia and 22 sickle cell homozygotes with a
      normal alpha-globin genotype from western India. The presence of alpha
      thalassaemia resulted in significantly higher haemoglobin (Hb), haematocrit
      (HCT), red blood cells counts (RBC) and haemoglobin A2 (HbA2) levels but lower
      mean cell haemoglobin (MCH) and mean cell volume (MCV). The clinical presentation
      in these patients was also milder with fewer episodes of painful crisis, chest
      syndromes, infections, requirement of hospitalization and blood transfusions.
      However, splenomegaly was more common as compared to the patients with a normal
      alpha-globin genotype. It is evident from the present study that alpha
      thalassaemia could be an important genetic factor modulating the clinical
      expression and haematological severity of sickle cell anaemia in this region.

PMID- 9604546
TI  - Utility of XY-amelogenin gene primers for detection of sex chromosomes.
AB  - The utility of polymerase chain reaction (PCR) amplification of amelogenin gene
      as a reliable and rapid means of determination of sex chromosomes was tested in
      20 patients of X-linked disorders (Duchenne muscular dystrophy, haemophilia and
      Wiscott-Aldrich and Hunter's syndromes), 12 of intersex (testicular feminization
      syndrome, male pseudohermaphrodites, true hermaphrodites) and 21 of congenital
      adrenal hyperplasia. Of these, 26 (49%) cases were for prenatal diagnosis of X
      linked diseases and congenital adrenal hyperplasia (CAH). The presence of X and Y
      chromosomes was determined within 24 h of receiving the samples. The results were
      in conformity with cytogenetic studies in all instances. The analysis of
      amelogenin gene proved helpful in the diagnosis and management of these patients.

PMID- 9604547
TI  - Correlation of clinical profile of myotonic dystrophy with CTG repeats in the
      myotonin protein kinase gene.
AB  - The molecular genetic analyses (PCR and Southern hybridization) of Indian
      patients with myotonic dystrophy (DM) were carried out to determine the degree of
      repeat expansion and an attempt was made to correlate the repeat number with
      disease severity. A scoring system based on the salient clinical features was
      devised to objectively assess the disease severity. The repeat expansion was seen
      in 11 of 12 patients examined and showed an inverse correlation with the age of
      onset confirming the phenomenon of anticipation. This was further established in
      the two pedigrees studied, clearly demonstrating both clinical and genetic
      anticipation. The clinical severity score, however, did not correlate well with
      the repeat number. Nonetheless, such molecular genetic analyses may have immense
      value as a screening procedure to identify premutations as well as in prenatal
      diagnoses.

PMID- 9604548
TI  - Structural relationships among dimensions of the DSM-IV anxiety and mood
      disorders and dimensions of negative affect, positive affect, and autonomic
      arousal.
AB  - Using outpatients with anxiety and mood disorders (N = 350), the authors tested
      several models of the structural relationships of dimensions of key features of
      selected emotional disorders and dimensions of the tripartite model of anxiety
      and depression. Results supported the discriminant validity of the 5 symptom
      domains examined (mood disorders: generalized anxiety disorder, GAD; panic
      disorder; obsessive-compulsive disorder; social phobia). Of various structural
      models evaluated, the best fitting involved a structure consistent with the
      tripartite model (e.g., the higher order factors, negative affect and positive
      affect, influenced emotional disorder factors in the expected manner). The latent
      factor, GAD, influenced the latent factor, autonomic arousal, in a direction
      consistent with recent laboratory findings (autonomic suppression). Findings are
      discussed in the context of the growing literature on higher order trait
      dimensions (e.g., negative affect) that may be of considerable importance to the
      understanding of the pathogenesis, course, and co-occurrence of emotional
      disorders.

PMID- 9604549
TI  - Implicit and explicit memory for shape, body weight, and food-related words in
      patients with anorexia nervosa and nondieting controls.
AB  - Twelve patients with anorexia nervosa and 12 control participants watched a
      series of 64 words. There were 4 word types: anorexia related, positive,
      negative, and neutral. The last 3 types were anorexia unrelated. Anorexia-related
      words had the same affective valence as the neutral control words. Next, the
      participants completed an explicit memory test (cued recall) and an implicit
      memory test (word stem completion). Results showed a strong explicit memory bias
      for anorexia-related words for patients with anorexia nervosa but not for
      nondieting controls. There was no evidence for a similar bias in implicit memory.
      Results are discussed in the context of cognitive biases in psychopathology.

PMID- 9604550
TI  - Attributional style and self-esteem: the prediction of emotional distress
      following a midterm exam.
AB  - A midterm design was used to determine whether students' attributional style for
      negative achievement events interacts with self-esteem and a lower-than-expected
      exam grade to predict changes in measures of specific and nonspecific depression
      and anxiety. Participants were 141 students who completed baseline measures of
      attributional style and self-esteem, as well as affective measures on several
      occasions before and after receipt of midterm grades. A pessimistic attributional
      style for negative events interacted with self-esteem and outcome to predict
      residual changes in a combined measure of nonspecific distress and anxious
      arousal (marginal trend) but not a combined measure of specific depressive
      symptoms. Unexpectedly, the greatest residual increases in distress occurred
      among low-self-esteem pessimists who experienced a nonfailure outcome. These
      effects did not appear to be mediated by changes in hopelessness.

PMID- 9604551
TI  - The structure and stability of common mental disorders (DSM-III-R): a
      longitudinal-epidemiological study.
AB  - The latent structure and stability of 10 common mental disorders were examined in
      a birth cohort at ages 18 and 21. A 2-factor model, in which some disorders were
      presumed to reflect internalizing problems and others were presumed to reflect
      externalizing problems, provided a more optimal fit to the data than either a 1-
      or a 4-factor model. To a significant extent, persons in the sample retained
      their relative positions on the latent factors across the 3-year period from age
      18 to age 21. Results offer potential clarification of the meaning of comorbidity
      in psychopathology research by suggesting that comorbidity may results from
      common mental disorders being reliable, covariant indicators of stable,
      underlying "core psychopathological processes."

PMID- 9604552
TI  - Electrodermal activity and obstetric complications in schizophrenia.
AB  - The pregnancy and birth records of 79 schizophrenic patients, from whom adult
      electrodermal data were available, were systematically evaluated for obstetric
      complications using 34 criteria of nonoptimality in pregnancy, delivery, and
      postpartum periods. Patients with many obstetric complications had lower levels
      of electrodermal activity. For frequency of skin conductance responses and
      spontaneous fluctuations in skin conductance, the association was more evident
      for women than for men. However, the ratio of stimulus-elicited to spontaneous
      skin conductance responses showed a reliable association with obstetric
      complications without any gender differences. The relationship between obstetric
      complications and electrodermal activity was interpreted in terms of
      neurodevelopmental insults resulting in structural brain abnormalities
      interfering with orienting and electrodermal activity.

PMID- 9604553
TI  - Profiles in discouragement: two studies of variability in the time course of
      smoking withdrawal symptoms.
AB  - Research has suggested that the time course of the smoking withdrawal syndrome is
      fairly invariant across smokers and that smoking withdrawal symptoms are weakly
      related to relapse. Withdrawal data from 2 clinical trials of the nicotine patch
      were analyzed to evaluate these characterizations. In both studies, patients were
      clustered according to the shapes of their withdrawal profiles across 8 weeks of
      treatment. In each study, 3 clusters with distinct temporal patterns of
      withdrawal symptomatology emerged. Clusters included both abstinent and lapsing
      patients, and patch dose was unrelated to cluster membership. Patients with
      "atypical" patterns of smoking withdrawal (e.g., late symptomatic elevations)
      were more likely to relapse than patients who showed a gradual elimination of
      withdrawal. Withdrawal shape, duration, and severity all contributed
      significantly to the prediction of relapse. Measures of negative affect closely
      tracked withdrawal symptoms over time within clusters. Topics for future smoking
      withdrawal research are discussed.

PMID- 9604554
TI  - The relation between personality and anxiety: findings from a 3-year prospective
      study.
AB  - The authors tested the extent to which the personality dimensions of neuroticism,
      extraversion, and psychoticism (H. J. Eysenck & S. B. G. Eysenck, 1975)
      prospectively predicted global anxiety (assessed by items from the Brief Symptom
      Inventory: L. R. Derogatis & M. S. Spencer, 1982). The authors also examined
      prospective relations among these personality dimensions and depression to
      evaluate the specificity of findings. Participants were 466 young adults,
      primarily undergraduate students, assessed twice over a 3-year interval. An
      interaction between neuroticism and extraversion predicted both global anxiety
      and depression 3 years later. Findings indicated that personality, in particular
      the combination of high neuroticism and low extraversion, may play an important
      predisposing, etiological role in anxiety. Interpretations and implications of
      the predictive importance of the Neuroticism x Extraversion interaction in
      anxiety are discussed, and further speculations about the relation between
      anxiety and depression are put forth.

PMID- 9604555
TI  - On the relation of dieting and bingeing in bulimia nervosa.
AB  - The continuum model of bulimia nervosa suggests that dieting plays a major role
      in the etiology and maintenance of bulimia. However, a previous study (M. R. Lowe
      et al., 1996) recently found no relationship between dieting intensity and binge
      eating problems in nonclinical participants differing widely in eating and weight
      concerns. The present study extended these findings by examining the relationship
      between dieting and bingeing among individuals with bulimia. Three samples of
      individuals diagnosed with bulimia were divided into frequent and infrequent
      weight-loss dieters and were compared on multiple measures of binge eating. No
      diet-binge relationship was found in 1 sample, whereas in the other 2 samples
      frequent dieters binged less than infrequent dieters. These results raise new
      questions about the continuum model of bulimia and suggest that weight-loss
      dieting may not play as prominent a role in the maintenance of bulimia as it does
      in its initiation.

PMID- 9604556
TI  - Identifying dissociative identity disorder: a self-report and projective study.
AB  - This study compared 21 female adult psychiatric patients diagnosed with
      dissociative identity disorder (DID) with 21 female adult nondissociative
      psychiatric patients to determine whether DID patients exhibit a distinguishing
      set of clinical features, and perceptual, attentional, and cognitive processes.
      Participants were assessed with the Dissociative Disorders Interview Schedule to
      assess diagnostic status. Group scores on the Dissociative Experiences Scale,
      Tellegen Absorption Scale, Childhood Trauma Questionnaire, Brief Symptom
      Inventory, and the Rorschach test were compared. DID participants reported
      earlier and more severe childhood trauma, more dissociative symptoms, and a
      greater propensity for altered states of consciousness. The DID participants also
      exhibited increased projective and imaginative activity, a diminished ability to
      integrate mental contents, a complex and driven cognitive style, and a highly
      unconventional view of reality.

PMID- 9604557
TI  - Automatic activation and strategic avoidance of threat-relevant information in
      social phobia.
AB  - The authors examined the hypothesis that abnormalities in activation and
      inhibition of threat-relevant information may account for information-processing
      biases in social anxiety. Individuals with generalized social phobia (GSP) and
      nonanxious controls were presented with sentences ending in homographs and in
      nonhomographs and were asked to make decisions about a cue word that followed
      each sentence. Half of the homographs had a social-threat implication. Longer
      response latency to make decisions about sentences ending in homographs compared
      with sentences ending in nonhomographs is thought to reflect activation of the
      inappropriate meaning of the homographs. Results revealed that GSPs showed
      initial activation of inappropriate meanings of socially relevant homographs
      followed by later inhibition of these meanings. These findings are consistent
      with a vigilance-avoidance model of information processing of threat-relevant
      information in social phobia.

PMID- 9604558
TI  - Response intensity in content-specific fear conditioning comparing 20% versus 13%
      CO2-enriched air as unconditioned stimuli.
AB  - This study examined the relation between the intensity of CO2-induced
      psychophysiological responses and content-specific fear conditioning. Sex
      balanced groups of undergraduates (N = 96) were assigned to 1 of 3 conditioned
      stimuli (CSs) differing in fear-relevance, and within each CS, to either 20% or
      13% CO2-enriched air (unconditioned stimuli [UCS]). Several psychophysiological
      measures were assessed before, during, and following conditioning phases.
      Consistent with expectation, electrodermal and cardiac conditioned responses were
      larger and more resistant to extinction when associated with fear-relevant
      compared with fear-irrelevant stimuli, and this overall effect of fear-relevance
      was more robust to the more intense UCS. Severity and frequency of DSM-IV
      (Diagnostic and Statistical Manual of Mental Disorders, 4th ed.) panic symptoms
      also varied reliably with UCS intensity, and women reported more distress and
      symptoms than men. Overall, the findings suggest that content-specific fear
      conditioning is mediated, in part, by the intensity of the bodily response. The
      authors discuss clinical and theoretical implications for understanding fear
      onset in the absence of obvious environmental pain or trauma.

PMID- 9604559
TI  - Comorbid mental disorders: implications for treatment and sample selection.
AB  - Disorders from the Diagnostic and Statistical Manual of Mental Disorders (3rd
      ed., rev.; American Psychiatric Association, 1987) were assessed in a birth
      cohort of 961 young adults. Comorbid cases exceeded single-disordered cases in
      chronic history of mental illness, use of treatments, physical health problems,
      functional interference in daily life, and impaired adaptation across domains
      such as work, education, health, and social-support networks. Single-disorder
      cases were also more impaired than nondisordered cases, but comorbid cases were
      the most severely impaired. Our findings suggest that (a) samples that
      underrepresent comorbidity (pure single-disorder cases or student samples) will
      underestimate effect sizes for relations between a disorder and its correlates,
      whereas samples that overrepresent comorbidity (clinical or adjudicated samples)
      will overestimate effect sizes, (b) comorbidity is accompanied by complications
      that challenge treatment planning, compliance, and coordination of service
      delivery, and (c) comorbidity is associated with physical, educational, and
      economic problems that make it a broad societal concern.

PMID- 9604560
TI  - Effects of false weight feedback on mood, self-evaluation, and food intake in
      restrained and unrestrained eaters.
AB  - Restrained and unrestrained eaters were weighted 5 lb (2.27 kg) heavier or 5 lb
      lighter than their actual weight or were not weighed at all. Unrestrained eaters
      and restrained eaters who were told they weighed 5 lb less were not affected by
      the false weight feedback. However, restrained eaters who were informed that they
      weighted 5 lb more reported lower self-esteem, less positive moods, and more
      negative moods than did restrained eaters in the other 2 conditions. Furthermore,
      restrained eaters who were led to believe that they weighed heavier ate
      significantly more food during a subsequent "taste test" than did each of the
      other groups. Restrained eaters who believed that they were heavier experienced
      lowered self-worth and a worsening of mood that led them to relinquish their
      dietary restraint and overindulge in available food. Implications for patients
      with eating disorders are discussed.

PMID- 9604561
TI  - Depressive personality: associations with DSM-III-R mood and personality
      disorders and negative and positive affectivity, 30-month stability, and
      prediction of course of Axis I depressive disorders.
AB  - The authors addressed 5 issues bearing on the validity of the construct of
      depressive personality disorder (DPD): its relationship with the Diagnostic and
      Statistical Manual of Mental Disorders (3rd ed., rev.; American Psychiatric
      Association, 1987) mood and personality disorders and normal personality
      dimensions of negative and positive affectivity, its stability over 30-months,
      and its impact on the course of Axis I depressive disorders. Two samples were
      used: 156 outpatients with mood disorders, personality disorders, or both, and
      267 of their 1st-degree relatives. The association between DPD and dysthymia was
      fairly modest, whereas the associations with major depression and the personality
      disorders were quite low. DPD was moderately correlated with both negative and
      positive affectivity; however, it contributed unique information beyond that
      available from the 2 emotional superfactors. Finally, DPD was moderately stable
      over a 30-month period and was associated with a poorer course of depression.

PMID- 9604562
TI  - Manual and saccadic reaction time with constant and variable preparatory
      intervals in schizophrenia.
AB  - Saccadic reaction time (RT) has been shown to be unimpaired in schizophrenia.
      Could this be due to its not requiring controlled information processing? The
      authors gave 49 schizophrenia patients and 34 controls manual and saccadic RT
      tasks with preparatory intervals of 1, 3, and 5 s given in regular and irregular
      sequences. If saccades require mainly automatic processes, they should not be
      affected by variations in the preparatory interval that are mediated by
      controlled processing. The manual task showed typical slower RT and larger
      preparatory interval effects in patients than in controls. Although the saccadic
      task showed significant effects of both the preparatory interval and the
      preparatory interval on the preceding trial similar in kind to those in manual
      RT, there were no group differences in these or in RT. The results are attributed
      to greater stimulus-response compatibility in the saccadic task, which puts fewer
      demands on working memory.

PMID- 9604563
TI  - Thirty-month naturalistic follow-up study of early-onset dysthymic disorder:
      course, diagnostic stability, and prediction of outcome.
AB  - Dysthymic disorder (DD) is defined and distinguished from major depressive
      disorder (MDD) largely on the basis of its course. Surprisingly, however, there
      have been few prospective, longitudinal studies of the naturalistic course of DD.
      This article reports the major findings from a prospective, longitudinal 30-month
      follow-up study of 86 outpatients with early-onset DD (EOD) and 39 outpatients
      with episodic MDD. Follow-up assessments included the Longitudinal Interval
      Follow-Up Evaluation and Hamilton Rating Scale for Depression. Compared with
      patients with episodic MDD, patients with EOD exhibited less improvement from the
      baseline evaluation and were more symptomatic at follow-up. Only 39% of patients
      with EOD recovered from DD during the follow-up period. The diagnosis of DD was
      fairly stable, with 52% of the EOD group meeting full criteria for DD at follow
      up. These data provide prospective confirmation of the chronic course of DD.

PMID- 9604564
TI  - Depressive personality characteristics: state dependent concomitants of
      depressive disorder and traits independent of current depression.
AB  - Depressive personality disorder (DPD) characteristics may reflect both state
      dependent concomitants and traits independent of current depression. In all, 30
      clinically, 30 formerly, and 30 never depressed participants were given the
      Diagnostic Interview for Depressive Personality (J. G. Gunderson, K. A. Phillips,
      J. Triebwasser, & R. M. A. Hirschfeld, 1994). Negative reactivity,
      remorsefulness, a limited capacity for fun, gloominess, pessimism, difficulty
      being critical or angry, unassertiveness, self-denial, and seriousness
      differentiated depressed and nondepressed participants, indicating that they are
      primarily concomitants of depression. Self-criticalness differentiated formerly
      from never depressed participants after subclinical symptoms were controlled,
      suggesting that it is a trait independent of current depression. Low self-esteem,
      feeling burdened, and counterdependency manifested both state and trait
      components. If DPD is placed on Axis II, it should be defined by traits at least
      partly independent of depression.

PMID- 9604565
TI  - Expressed emotion, attributions, and schizophrenia symptom dimensions.
AB  - Using a sample of 40 Anglo American family members of schizophrenic patients, the
      present study replicates and lends cross-cultural support for an attribution
      affect model of expressed emotion (EE). Consistent with attribution theory, the
      authors found that highly critical relatives (high-EE) viewed the illness and
      associated symptoms as residing more within the patient's personal control as
      compared with less critical relatives (low-EE). A content analysis classified the
      types of behaviors and symptoms most frequently criticized by relatives. Symptoms
      reflecting behavioral deficits (e.g., poor hygiene) were found to be criticized
      more often than symptoms reflecting behavioral excesses (e.g., hallucinations).
      In line with an attribution-affect framework, relatives may be less tolerant of
      behavioral deficits because they are viewed as intentional, whereas behavioral
      excesses are easily recognized as core symptoms of mental illness.

PMID- 9604566
TI  - Pragmatic directions and children's word learning.
AB  - The present study tested the hypothesis that children as young as two use what
      adults tell them about meaning relations when they make inferences about new
      words. 18 two-year-olds (mean age 2;2) and 18 three-year-olds (mean age 3;2)
      learned two new terms (a) with instructions either (i) to treat one term as a
      superordinate to the other, or (ii) to replace one term with another; and (b)
      with no instruction given about how two new words might be related. Children were
      attentive to both kinds of instructions or pragmatic directions, and made use of
      them in their word-learning. When they received no instruction relating the two
      new words, they resorted to a range of coping strategies to assign and relate
      meanings to each other. These findings support the view that children's learning
      of new word meanings is guided by the pragmatic directions adults offer.

PMID- 9604567
TI  - Generic noun phrases in mother-child conversations.
AB  - Generic noun phrases (e.g. Tigers are fierce) are of interest for their semantic
      properties: they capture 'essential' properties, are timeless, and are context
      free. The present study examines use of generic noun phrases by preschool
      children and their mothers. Mother-child pairs were videotaped while looking
      through a book of animal pictures. Each page depicted either a single instance of
      a particular category (e.g. one crab) or multiple instances of a particular
      category (e.g. many crabs). The results indicated a striking difference in how
      generics vs. non-generics were distributed, both in the speech of mothers and in
      the speech of preschool children. Whereas the form of non-generic noun phrases
      was closely linked to the structure of the page (i.e. singular noun phrases were
      used more often when a single instance was presented; plural noun phrases were
      used more often when multiple instances were presented), the form of generic noun
      phrases was independent of the information depicted (e.g. plural noun phrases
      were as frequent when only one instance was presented as when multiple instances
      were presented). We interpret the data as providing evidence that generic noun
      phrases differ in their semantics and conceptual organization from non-generic
      noun phrases, both in the input to young children and in children's own speech.
      Thus, this simple linguistic device may provide input to, and a reflection of,
      children's early developing notion of 'kinds'.

PMID- 9604568
TI  - Subject-verb agreement in Brazilian Portuguese: what low error rates hide.
AB  - This study focuses on the acquisition of subject-verb agreement in Brazilian
      Portuguese. A quantitative analysis of the data produced by a Brazilian child
      between the ages of 3;02.07 and 3;04.08 is presented. The overall error rate is
      low. However, a further and more detailed analysis reveals important contrasts
      both in the frequency of production of different verb inflections (as regards the
      person/number variables within the verb morphological system) and in the rate of
      subject-verb agreement errors associated with them. Our findings not only suggest
      that subject-verb agreement may be acquired piecemeal, but also that the learning
      of particular verb inflections may itself be a gradual process. Alternatives to
      the idea of rule-governed production--such as the child's reproducing frozen
      subject-verb strings previously produced by adults and blending different frozen
      strings into novel combinations--are discussed as processes which can shed some
      light on the pattern of both erroneous and correct production shown by this
      child.

PMID- 9604569
TI  - On the characterization of a chain shift in normal and delayed phonological
      acquisition.
AB  - Several theoretical and descriptive challenges are presented by children's
      phonological substitution errors which interact to yield the effect of a chain
      shift. Drawing on an archival study of the sound systems of five children (ages
      3;5 to 4;0) with normal development and 47 children (ages 3;4 to 6;8) with
      phonological delay, one such chain shift, namely the replacement of target
      /theta/ by [f] and the replacement of /s/ by [theta], was identified in the
      speech of six children from the two subgroups. Different derivational and
      constraint-based accounts of the chain shift were formulated and evaluated
      against the facts of change and the children's presumed perceptual abilities. An
      adequate account in either framework was found to require the postulation of
      underspecified and, in some instances, nonadult-like underlying representations.
      Such representations were able to reconcile within a single-lexicon model the
      presumed production/perception dilemma commonly associated with acquisition.
      Continuity was also preserved by limiting underlying change to just those lexical
      items which exhibited a change phonetically.

PMID- 9604570
TI  - Why are some verbs learned before other verbs? Effects of input frequency and
      structure on children's early verb use.
AB  - This study investigated the extent to which the nature of verb input accounts for
      the order in which children acquire verbs. We assessed the nature of verb input
      using a combined sample of the speech of 57 mothers addressing their Stage I
      children. We assessed the order of verb acquisition using as our database a
      combined sample of those children's speech 10 weeks later and using as our
      measure of order of acquisition the frequency of verb occurrence. The first set
      of analyses established the validity of this measure of acquisition order by
      comparing it with order of acquisition data obtained from checklist and diary
      data. The second set of analyses revealed that three properties of the input were
      significant predictors of the order of acquisition of the 25 verbs that were the
      focus of this study. The predictive properties of input were the total frequency,
      final position frequency, and diversity of syntactic environments in which the
      verbs appeared. These findings suggest that the way verbs appear in input
      influences their ease of acquisition. More specifically, the effect of syntactic
      diversity in input provides support for the syntactic bootstrapping account of
      how children use structural information to learn the meaning of new verbs.

PMID- 9604571
TI  - The prevalence and the weakness of an early name mapping preference.
AB  - An empirical puzzle regarding toddlers' fast mapping motivated the current
      investigation. Whereas children between 1;10 and 2;1 have shown only a modest
      rate of mapping novel nouns onto unfamiliar rather than familiar objects, a very
      high rate has been observed in those between 1;4 and 1;8 (Mervis & Bertrand,
      1991). Study 1 examined whether young two-year-olds (N = 40, mean age = 2;1)
      might map at a higher rate when tested with procedures unique to Mervis &
      Bertrand's assessment--strong corrective feedback rather than mild positive non
      contingent feedback; large sets of test objects rather than pairs; presentation
      of easier tests first. Only the first variable affected performance in a manner
      that could solve the puzzle. Unfamiliar kinds were selected at a much higher rate
      under corrective (0.86) than non-contingent (0.57) feedback. Although nearly
      every child in the non-contingent group chose correctly on the first trial, many
      failed to do so thereafter. In Study 2, rather than presenting a test word to the
      children (N = 16, mean age = 2;2), the experimenter merely asked for 'the one I
      want'. Unfamiliar kinds were selected much less often than in Study 1, suggesting
      that at least one lexical principle proposed in the literature underlies the noun
      mapping preference. Changes over trials in the two studies indicated that the
      noun mapping preference is quite prevalent, but unless initial choices are
      strongly reinforced, an increase in the salience of familiar kinds after the
      first trial lures some children into error. Consistent with this analysis,
      toddlers in Study 3 (N = 24, mean age = 2:1) who received non-contingent strong
      acceptance for their noun mapping decisions, selected unfamiliar kinds more often
      than those who had received non-contingent mild acceptance in Study 1.

PMID- 9604572
TI  - Communicative styles of mothers interacting with their preschool-age children: a
      factor analytic study.
AB  - The aim of this study was to determine if mothers display identifiably different
      communicative styles in their interaction with their normally developing two- to
      five-year-old children. In order to investigate this issue an extensive coding
      system was developed, which assessed the structural organization and the
      communicative function of the speech of 71 mothers as they interacted with their
      children. By means of factor analysis three maternal communicative styles were
      distinguished: non-intervening, explaining and directing. In the non-intervening
      style there is no direct pressure from the mother on the child to respond
      verbally. The explaining mother is primarily concerned with providing information
      to her child in a way that gives the child little opportunity to take the
      speaking turn. The directing mother is mainly engaged in directing the child's
      behaviour by means of verbal control. The internal consistency of the three
      communicative styles appeared to be both satisfactory and related to relevant
      child and mother features.

PMID- 9604573
TI  - Phonological and acoustic bases for earliest grammatical category assignment: a
      cross-linguistic perspective.
AB  - Maternal infant-directed speech in Mandarin Chinese and Turkish (two mother-child
      dyads each; ages of children between 0;11 and 1;8) was examined to see if cues
      exist in input that might assist infants' assignment of words to lexical and
      functional item categories. Distributional, phonological, and acoustic measures
      were analysed. In each language, lexical and functional items (i.e. syllabic
      morphemes) differed significantly on numerous measures. Despite differences in
      mean values between categories, distributions of values typically displayed
      substantial overlap. However, simulations with self-organizing neural networks
      supported the conclusion that although individual dimensions had low cue
      validity, in each language multidimensional constellations of presyntactic cues
      are sufficient to guide assignment of words to rudimentary grammatical
      categories.

PMID- 9604574
TI  - Young children's understanding of promising: methodological considerations.
AB  - In her inceptive study of promising, Astington (1988) found that five-year-olds
      failed to distinguish promises from predictions when judging story characters'
      utterances. Instead, their responses were based on whether the promised event had
      actually occurred. There is reason to believe, however, that the children's poor
      performance was an artefact of Astington's procedures. We tested this possibility
      with 32 children (mean age 5;8: range 5;7-6;2) by including several variations of
      Astington's procedures, but found no effects on the pattern of results. This
      suggests that Astington's findings are an accurate reflection of the
      developmental course of knowledge about promising.

PMID- 9604575
TI  - Polymerization shrinkage and polymerization shrinkage stress in polymer-based
      restoratives.
AB  - OBJECTIVES: This paper is intended to contribute to the recognition and
      understanding of problems related to polymerization shrinkage. DATA SOURCES:
      Scientific publications of relevance with regard to this subject were critically
      reviewed. STUDY SELECTION: The dimensional changes which develop during the
      curing of resin composites and glass polyalkenoate cements are studied, with
      special reference to methods of determining shrinkage, shrinkage stress and
      stress relief. CONCLUSIONS: As no method for handling the adhesive restorative
      materials has yet been described which guarantees a leakproof restoration, the
      practitioner has to accept the problem of polymerization shrinkage and
      destructive shrinkage stress. Only a proper understanding of the mechanisms that
      cause these problems and the techniques that may reduce their effects will enable
      the practitioner to derive maximum benefit from the application of resin
      composites and glass polyalkenoate cements in restorative dentistry.

PMID- 9604576
TI  - The dentin substrate: structure and properties related to bonding.
AB  - OBJECTIVES: Dentin is a vital, hydrated composite material with structural
      components and properties that vary with location. These variations are reviewed
      along with alterations by physiological and pathological changes that allow
      classification into various forms of dentin. Structural characteristics and
      mechanical properties are reviewed and the limitations of our understanding of
      structure-property relationships for normal and modified forms of dentin are
      discussed with respect to their impact on dentin bonding. Recent progress in
      methods available to study dentin and its demineralization are emphasized with
      their promise to increase our understanding of dentin properties and structure.
      DATA SOURCES: Recent microstructural studies, focusing on scanning electron
      microscopy, atomic force microscopy and X-ray tomographic microscopy are
      included. A review of fundamental studies with emphasis on microstructurally
      sensitive methods, and prior reviews of basic mechanical properties are included
      with discussion of their correlation to composition and structure. STUDY
      SELECTION AND CONCLUSIONS: Emphasis in this work was placed on the major
      structural components of the tissue, including the collagen based organic matrix
      and its mineral reinforcement, the distribution of these components and their
      microstructural organization as related to mechanical properties and response to
      demineralization. Little information is included on biochemical and developmental
      studies or on non-collagenous proteins and other organic components for which
      limited understanding is available with respect to their role in structure
      property relations and influence on bonding. In spite of the fact that the
      complexity of dentin precluded a comprehensive review, it is clear that local
      structural variations influence properties and impact nearly all preventive and
      restorative dental treatments. Much more work is needed in order to understand
      differences between vital and non-vital dentin, and dentin from extracted teeth.
      Although our knowledge is rudimentary in certain areas, increasingly
      sophisticated methods of studying dentin should provide the necessary information
      to model structure-property relations, optimize dentin bonding, and improve many
      aspects of preventive and restorative dentistry.

PMID- 9604577
TI  - Benefits and disadvantages of tooth-coloured alternatives to amalgam.
AB  - OBJECTIVES: To give the practising dentist scientifically based data to assist
      him/her in the responsible decision-making process necessary to weigh the options
      available to the patient if she/he prefers not to have an amalgam placed. DATA
      SOURCES: Based on the literature and on the research work, which was done in the
      author's department, the indications and limitations of the known alternatives of
      amalgam were formulated. DESCRIPTION OF ALTERNATIVES TO AMALGAM: With the
      exception of cast gold restorations, all alternatives require the strict use of
      adhesive techniques. When compared with similar amalgam restorations, placing
      composite restorations (if they are indicated) takes approximately 2.5 times
      longer because complex incremental techniques are needed. Despite all the
      efforts, direct composite restorations placed in large cavities still show
      unacceptable amounts of marginal openings. Tooth-coloured inlays are a better
      alternative for large restorations. These restorations must be inserted with
      adhesive techniques. With composite inlays it is difficult to achieve a composite
      composite bond. Ceramic inlays may be micromechanically bonded to the luting
      composite. They all show clinically a good marginal behaviour and the use of
      ultrasonic energy may further simplify the application technique of aesthetic
      inlays. STUDY SELECTION: Papers describing the different techniques were used as
      a base for the corresponding chapter. To assess and compare the longevity of the
      different restoration types, literature data were used. We limited ourselves to
      papers reporting at least 5-year clinical data. Longitudinal, clinically
      controlled studies were preferred. However, to be more complete, retrospective,
      cross sectional studies were also included. LONGEVITY OF POSTERIOR RESTORATIONS:
      Amalgam shows excellent longevity data with studies up to 20 years. The average
      annual failure rate is 0.3-6.9%. Posterior composites are in the same range (0.5
      6.6%), however, the study times are much shorter (max. 10 years). For tooth
      coloured inlays much less data are available. Longevity is reported up to 6 years
      with annual failure rates of 0.6-5%. CONCLUSIONS: All aesthetic alternatives to
      amalgam require more complex procedures and more time. If cost benefit
      considerations are a concern, amalgam is still the most convenient restorative
      material for posterior teeth.

PMID- 9604578
TI  - Artificial salivas for in vitro studies of dental materials.
AB  - OBJECTIVES: An artificial saliva (AS) of defined composition is necessary for
      testing the performance of materials that serve in the mouth as natural saliva is
      too variable. The chemistry involved is critically important. Many AS recipes can
      be found in the literature, but the stability of tooth material, i.e.
      hydroxyapatite (HAP), in most of these has not been addressed. In fact, few
      contain all major ionic components with concentrations in the physiological
      range. The aim of the present study was (a) to review reported AS formulae from
      their inception in 1931 to date, (b) to compare the stability of HAP in various
      reported AS, and (c) to investigate the individual effects of ionic components
      present in the reported formulae on the stability of HAP. METHODS: A computer
      algorithm, RAMESES, for solving multiple equilibrium equations, was employed for
      all calculations. RESULTS: There was a marked difference between two groups, i.e.
      those with and without the presence of Ca; those with Ca were supersaturated with
      respect to HAP in the physiological pH range, the saturation pH ranging from
      about 4.5 to 6.0. There was also an approximately 180-fold range in solubility at
      pH 7, due to the individual effects of components such as phosphate, carbonate
      and citrate. Acetate, lactate and sulphate showed smaller effects, others have no
      appreciable effect. CONCLUSIONS: All components and equilibria of relevance to
      saliva must be included in the system for detailed models. Continued systematic
      development of a standardized AS is essential.

PMID- 9604579
TI  - 3D-FEA of osseointegration percentages and patterns on implant-bone interfacial
      stresses.
AB  - OBJECTIVES: The degree of osseointegration and its patterns are important for the
      success of implants. 3D-FEA was used to determine interfacial stresses on a
      single tooth implant (IMZ) for four degrees of osseointegration (100, 75, 50 and
      25%), and five patterns at 50% osseointegration (locally alternating, coronal
      only, apical only, facial only and lingual only). METHODS: The implant was
      restored with a metal-ceramic crown and subjected to 10 MPa axial or oblique
      applied stress. Resolved stresses were examined at four heights along the implant
      bone interface. RESULTS: The degree of osseointegration did not affect resolved
      stress levels or distributions. Oblique loads elevated interfacial stresses 5 to
      20 times. Stresses were always higher at the bone crest. CONCLUSIONS:
      Osseointegration patterns with crestal bone reduced both crestal and apical
      stresses. Apical only osseointegration produced much higher apical stresses.
      Crestal osseointegration and axial loads minimized overall stress.

PMID- 9604580
TI  - patients' satisfaction with different types of veneer restorations.
AB  - OBJECTIVES: The aim of this study was to measure the satisfaction of patients
      with respect to the aesthetics of veneer restorations (VRs) and to identify
      potential factors influencing their satisfaction. MATERIALS AND METHODS: One
      hundred and eighty VRs of three different types (direct composite, indirect
      composite and porcelain) were placed on anterior teeth. Patients were asked to
      fill in questionnaires at baseline and at one- and two-year recalls. RESULTS: At
      baseline the overall satisfaction was 76%, after two years this was 78%. The
      variable 'type of VR' was the only factor measured that had a significant
      influence on the satisfaction of the patient. At the two-year evaluation patients
      with porcelain VRs were more satisfied than those with direct composite VRs (P <
      0.05). CONCLUSIONS: From the results of this study it is concluded that
      differences in clinical procedures had no effect on satisfaction. Also the number
      of VRs had not influenced the level of satisfaction. After two years a
      significant difference was observed for the variable 'type of VR', with the best
      results for porcelain.

PMID- 9604581
TI  - Iodinated methacrylate copolymers as X-ray opaque denture base acrylics.
AB  - OBJECTIVES: The purpose of this study was to evaluate novel iodinated
      methacrylate copolymers as X-ray opaque denture base resins. METHODS: The
      synthesis of specific monomers and suspension copolymerization with methyl
      methacrylate to produce copolymer beads. The resulting beads were processed in an
      identical manner to standard PMMA to produce test-pieces for mechanical testing.
      RESULTS: Samples prepared from beads containing 25 wt% of the iodinated copolymer
      exhibited an X-ray opacity equivalent to that exhibited by a similar thickness of
      aluminium. Furthermore, the appearance and mechanical properties were comparable
      to standard PMMA, while thermal stability proved superior. CONCLUSION: These
      novel iodinated methacrylate monomers show promise not only as polymerizable
      additives to methyl methacrylate to produce an X-ray opaque denture base but also
      as thermally stable copolymerizable additives to other applications where X-ray
      opacity would be advantageous.

PMID- 9604582
TI  - On mentors, epitaphs & patients. What it takes to become a beloved physician.

PMID- 9604583
TI  - All bull. part II: Just "B Kool".

PMID- 9604584
TI  - Assisted hatching of embryos by micromanipulation for human in vitro
      fertilization: UAMS experience.
AB  - In vitro fertilization and embryo transfer (IVF) is utilized as a treatment for
      infertile couples who cannot conceive with standard therapy. Assisted hatching
      (AH) is a procedure whereby an opening is made in the zona pellucida of the
      embryos, thereby increasing the probability of implantation and pregnancy. AH is
      beneficial in patients with elevated FSH levels, older than age 38 or those who
      failed IVF repeatedly. Success rates after IVF with AH at the University of
      Arkansas for Medical Sciences (UAMS) compares favorably with rates achieved by
      other centers in the USA. Pregnancy rates after IVF with AH in patients older
      than 38 years is approximately 20% compared to a pregnancy rate of 10% in
      patients who did not have AH. This report summarizes the UAMS experience with IVF
      and AH.

PMID- 9604585
TI  - Mental health in Arkansas.

PMID- 9604586
TI  - Hypertension and asthma. An AFMC project.

PMID- 9604587
TI  - Vasodepressor syncope.

PMID- 9604588
TI  - Tickborne diseases in Arkansas.

PMID- 9604589
TI  - DNA vaccines.

PMID- 9604590
TI  - Biparietal diameter, fetal maturity, and body weight in rural Tanzanian newborns.
AB  - The biparietal diameter (BPD) in 202 rural Tanzanian newborns was measured and
      correlated to maturity and body weight. The mean BPD at birth was 9.0 cm. The
      average body weight was 2642 g. Fetal maturity was determined by Petrussa score,
      serving as an estimate for gestational age. The mean gestational age of the 202
      newborns was 39 weeks. The average body weight of the mature babies (gestational
      age 38-40 weeks) was 2765 g. All babies less than 38 weeks of gestation were born
      with a low birth weight (LBW < or = 2500 g) except for one. The LBW-babies
      comprised 34 per cent of the total births. About two-thirds of all LBW-babies (62
      per cent) were born small for date, only 38 per cent preterm. Regression analysis
      of the data set was performed resulting in significant models of estimates of
      gestational age and body weight from BPD as well as body weight from gestational
      age. In a baby older than 35 weeks of gestation a body weight of more than 1500 g
      can be expected. With regard to maturity (> or = weeks) and body weight (> or =
      1500 g) there is a good chance of survival when the BPD exceeds 7.5 cm. The
      analysis of our data denotes that tables from industrialized countries relating
      gestational age to sonographically measured BPD are not applicable for
      pregnancies in developing countries.

PMID- 9604591
TI  - Sickle cell disease in Bahrain: coexistence and interaction with glucose-6
      phosphate dehydrogenase (G6PD) deficiency.
AB  - The object was to determine the frequency of glucose-6-phosphate dehydrogenase in
      Bahraini individuals with HbS as compared to those without HbS. Haemolysates of
      erythrocytes from 310 Bahraini individuals attending Health Centres were
      obtained, electrophoresed on cellulose acetate at PH 8.2-8.6, and stained for
      G6PD. HbS was present in 125 individuals (study group) and in 185 only HbA was
      present (control group). G6PD deficiency (very low to undetectable) was
      identified in 59 samples (47 per cent) of the study group and 35 (19 per cent) of
      the control group. A positive correlation between G6PD deficiency and HbS is
      present in Bahraini individuals tested. This is similar to the situation in the
      Eastern Province of Saudi Arabia. We speculate that the observation could be
      explained on the basis of historic endemicity of Falciparum malaria in both
      regions on the East coast of the Saudi Peninsula.

PMID- 9604592
TI  - Clinical manifestations of HIV infection in children at Enugu, Nigeria.
AB  - Three-hundred-and-fifty-eight (358) pediatric patients below 16 years of age were
      screened for suspected human immunodeficiency virus (HIV) infection between
      October 1989 and September 1996. Eighty-three (23 per cent) were confirmed
      positive. However, adequate clinical data were obtained retrospectively in only
      63 patients. Twenty-three (37 per cent) of the patients presented with features
      corresponding to WHO case definition of Paediatric Acquired Immunodeficiency
      syndrome (AIDS) in Africa. Vertical mode of infection was documented in 13 (30
      per cent) of them while 30 (68 per cent) were infected through blood transfusion.
      The main clinical features at presentation were generalised lymphadenopathy (59
      per cent), persistent or recurrent fever (51 per cent), progressive weight loss
      or poor weight gain (51 per cent), chronic diarrhoea (38 per cent), various skin
      manifestations (37 per cent), persistent cough (32 per cent), and oral
      candidiasis (19 per cent). Six patients died during the initial admission, while
      majority were lost to follow-up.

PMID- 9604593
TI  - Neuroblastoma in children: a 10-year experience in Saudi Arabia.
AB  - Twenty children with biopsy-proven neuroblastoma were diagnosed and treated
      between 1984 and 1994 at King Fahd Hospital of the University in Al-Khobar, Saudi
      Arabia. There were 12 males and eight females with a ratio of 1.5/1. The median
      age at diagnosis was 3 years. Clinical staging showed: Stage I, 0 per cent; Stage
      II, 30 per cent; Stage III, 30 per cent; Stage IV, 35 per cent, Stage IVs, 5 per
      cent. Primary sites of involvement included: adrenal 55 per cent retroperitoneal,
      15 per cent; thoracic, 10 per cent, cervical, 5 per cent; pharyngeal, 5 per cent;
      lumbar, 5 per cent; unknown, 5 per cent. Pathological features showed:
      neuroblastoma, 70 per cent; ganglio neuroblastoma, 25 per cent; ganglioneuroma, 5
      per cent. Clinical presentation revealed: abdominal swelling, 55 per cent; fever,
      40 per cent; weight loss, 35 per cent; anorexia, 25 per cent; proptosis, 20 per
      cent; opsomyoclonus, 5 per cent; skin nodules, 5 per cent; diarrhoea, 5 per cent.
      Twenty four-hour urine collection showed high level of VMA in 13 (65 per cent)
      patients. Follow-up was from 6 months-10 years (median 5 years). disease-free
      survival at 2 years were as followed: Stage II, 100 per cent; Stage III, 66 per
      cent; Stage IV, 14 per cent; Stage IVs, 100 per cent.

PMID- 9604594
TI  - Congenital hypothyroid screening: the Oman experience.
AB  - In September 1991, a pilot scheme was inaugurated to screen all babies born at
      the Royal and Khoula Hospitals for congenital hypothyroidism (CHT). By December
      1995, 36,000 babies were screened and 16 cases of congenital hypothyroidism were
      diagnosed. This suggests an incidence of 1:2200 which is higher than the reported
      incidence in Caucasian populations and similar to the incidence reported from
      Saudi Arabia. This report summarizes our experience for the first 5 years.

PMID- 9604595
TI  - Members of the throat microflora among infants with different feeding methods.
AB  - Normal throat microflora have an important role of antagonistic activity against
      pathogenic bacteria. We studied members of throat microflora of 30 exclusively
      breastfed, 15 mixed-fed and 15 exclusively formula-fed infants at the age of 1
      month. All infants harboured alpha haemolytic Streptococcus. The incidence of
      gamma Streptococcus and coagulase negative Staphylococcus's isolation from
      breastfed infants was higher. We also found that coagulase negative
      Staphylococcus is one of three predominant bacterial species in breastfed
      infants.

PMID- 9604596
TI  - Risk factors for the occurrence of bancroftian filariasis infection in children
      living in endemic areas of northeast of Brazil.
AB  - The objective of this study was to identify biological and social risk factors
      for the occurrence of microfilaraemia in a population of 1464 children of both
      sexes aged 5-14 years, living in two highly endemic areas of Recife a city in the
      northeast of Brazil. A survey was performed from December 1990 to July 1991 and
      the microfilaraemia was examined by the thick-drop technique using 45 microliters
      of peripheral blood. Information was obtained about use of bednet, length of time
      living in area and number of occupants per household. Risk was quantified by the
      crude and adjusted Odds Ratio. The 95 per cent confidence interval, Likelihood
      Ratio Statistics, and P value were used to test the statistical significance. An
      association was established between microfilaraemia in children and adolescents,
      and age, number of individuals per household, the presence of microfilaraemic
      adults in the household, length of time living in the area, and bednet use.
      Maternal microfilaraemia was not found to be a risk factor for the occurrence of
      microfilaraemia in offspring. These results allow the identification of children
      with a greater risk of microfilaraemia. In addition, these findings highlight the
      role of the household environment in the transmission process.

PMID- 9604597
TI  - Respiratory syncytial virus infection in infants hospitalized with respiratory
      illness in northern Jordan.
AB  - During the winter seasons of 1993 and 1994, a total of 256 nasopharyngeal
      aspirates (NPA) from infants aged less than 1 year old admitted to the pediatric
      ward of Princess Rahma Hospital, northern Jordan, with bronchiolitis and/or
      pneumonia, were tested for the presence of respiratory syncytial virus (RSV)
      using direct immunofluorescence assay (DFA) and cell culture (CC). Of the 256
      specimens, 129 (50 per cent) were found positive by both DFA and CC, whereas 24
      specimens (9 per cent) and 16 specimens (6 per cent) were found positive by DFA
      and CC, respectively. In an evaluation of the collected NPA specimens detected by
      DFA, a sensitivity of 89 per cent and a specificity of 78 per cent were
      demonstrated. These data suggest that virus isolation in CC is still important
      for the diagnosis of RSV, although DFA is a valuable, rapid diagnostic assay.

PMID- 9604598
TI  - Age and sex are important factors in determining normal retinol levels.
AB  - Cut-off levels for serum retinol levels of 20 micrograms/dl for marginal and 10
      micrograms/dl for definite deficiency have been advocated and extensively used in
      population studies. However, the blood serum levels of retinol of the newborn are
      known to be very low and although the age dependency of the retinol binding
      protein has been described, the normal levels of serum retinol at different ages
      have not been reported from larger series. While studying poor populations of
      young infants in Lahore, Pakistan, we thought it necessary to try to achieve
      appropriate reference values by analysing the levels of serum retinol of
      expatriates from the Indian subcontinent who live in the affluent United Arab
      Emirates, where retinol deficiency is not seen either at the hospital or the
      community levels. We have studied material, cord blood, infantile and adult
      levels of retinol and found a highly significant age relationship of serum
      retinol levels. During very early infancy the 'normal' mean is below what has
      been considered deficiency. This is new information and important in the
      evaluation of retinol status of individuals as well as populations. In addition,
      we found lower levels in women, pregnant or non-pregnant, than those in adult
      men. This sex difference in adults was not seen in infants. We recommend a cut
      off level for deficiency of 10 micrograms/dl, but only for those above 1 month of
      postnatal age.

PMID- 9604599
TI  - Viral aetiology and epidemiology of acute respiratory infections in hospitalized
      Saudi children.
AB  - A total of 1429 Saudi children of either sex and under 5 years of age who were
      admitted to King Khalid University Hospital, Riyadh during a three year period
      (April 1993-March 1996) with complaints suggestive of acute respiratory tract
      infections (ARTI) were investigated for viral aetiology of the infection. Viruses
      could be detected in 522 (37 per cent) cases with respiratory syncytial virus
      (RSV) the most commonly detected (79 per cent) followed by parainfluenza type 3
      (8 per cent). Detection of influenza A, B and adenoviruses accounted for 6 per
      cent, 3 per cent and 2 per cent respectively. Except for parainfluenza virus type
      3 the peak of activity of the respiratory viruses was during the winter months
      (October-February). Parainfluenza virus type 3 could be detected all year round
      but epidemics can occur in the hottest months of the year (June-August) when the
      temperature can exceed 40 degrees C. Association between clinical manifestation,
      type of causative agent, and age was evaluated in 137 infected Saudi children in
      the first year of the study (April 1993-March 1994). The majority of our cases
      presented with bronchiolitis (58 per cent) while only 26 per cent had
      bronchopneumonia. There was a significant association between bronchiolitis and
      lower age groups (0-6 months), with RSV as the major causative agent of
      bronchiolitis cases (88 per cent).

PMID- 9604600
TI  - Epidemiology of systemic candidiasis in a tertiary care neonatal unit.
AB  - 143 neonates were diagnosed to have acquired systemic candidiasis out of a total
      4530 admissions (3.2 per cent) to the neonatal intensive care unit (NICU) during
      a period of 6 1/2 years from January 1990 to June 1996. Mean age at onset was
      10.4 days, mean birth weight 1454 g, and mean gestation was 31.7 weeks. Ninety
      four per cent were premature, 95 per cent low birth weight (LBW), and all had
      undergone peripheral vein catheterization and had received broad spectrum
      antibiotics, except one, prior to the diagnosis. Fifty-eight per cent were
      ventilated and 15 per cent received parenteral nutrition. Persistent/recurrent
      pneumonia, apnoea, lethargy, high gastric aspirates, and abdominal distension
      were the common clinical manifestations. Candida tropicalis, C. albicans, and C.
      guillermondii were the most common isolates. Blood and urine were the predominant
      sites for isolation of Candida. Fluconazole was the most used antifungal agent,
      with 24 per cent resistance against it. Fifty per cent of babies died due to all
      causes. Of all the deaths, two-thirds were Candida related. Candida-attributable
      deaths occurred in 24 cases (17 per cent).

PMID- 9604601
TI  - Malaria prevalence and outcome in the in-patients of the Paediatric Department of
      the State Specialists Hospital (SSH), Maiduguri, Nigeria.
AB  - Of 4651 admissions between February 1995 and February 1996, 1043 had a presumed
      diagnosis of malaria. Six hundred and twenty-seven cases were confirmed by thick
      blood film examinations. The highest prevalence was in October (124/480
      admissions) and the lowest in March (12/303). Sixty-five children died while 562
      survived, 12 with defects. The first treatment in 422 children was chloroquine,
      in 143 quinine, in 59 halofantrin, and in three pyrimethamine with sulfadoxine
      (Fansidar). 23/422 patients started on chloroquine were switched to halofantrine,
      two to quinine. A higher mortality was associated with coma, convulsions,
      hepatosplenomegaly, pulmonary congestion, jaundice, haemoglobinuria, bladder
      paralysis, anuria. Anaemia and fever were more severe and hypoglycaemia more
      frequent in children who died than in children who survived (packed cell volume
      18.5 +/- 7.1 per cent vs. 25.6 +/- 7.6 per cent, p < 0.001; temperature 39 +/-
      1.1 degrees C vs. 38.7 +/- 0.9 degrees C, p < 0.05; random blood sugar < 40
      mg/100 ml; 76 vs. 22 per cent, p < 0.01). There was no difference in the median
      age, pretreatment duration, and prevalence of diarrhoea and sickle cell disease.
      The male to female ratio was 1.5:1 in the surviving children vs. 1:1.03 in the
      dead.

PMID- 9604602
TI  - Breastfeeding practices in urban Riyadh.
AB  - Three hundred and forty-seven mother-infant pairs attending a well baby clinic in
      a University Hospital in Riyadh were interviewed on the type of feeding given to
      their infants. The objective was to assess the latest trend of infant feeding
      practices in an urban population and to compare present trends and their
      significance with previous reports. Results showed that 32.4 per cent of infants
      at 3 months and 22.1 per cent of infants at 6 months were exclusively breastfed;
      18.2, 48.4, and 65.4 per cent were exclusively bottle fed at 3 months, 6 months,
      and 1 year respectively. Weaning foods were added between 3 and 6 months to a
      very high percentage of infants. Insufficient breast milk and refusal of breast
      by the infant were among the most common reasons for introduction of bottle
      feeds.

PMID- 9604603
TI  - Serum magnesium levels in protein-energy malnutrition.
AB  - Serum magnesium levels were measured by atomic absorption spectrophotometry in 46
      malnourished and 12 healthy children, aged 3 months to 5 years. The nutritional
      status of children was classified in relation to weight for age and height for
      age using the Indian Academy of Pediatrics and the Waterlow classifications,
      respectively. NCHS data were used for the purposes of comparison. Serum magnesium
      levels were significantly low in children with moderate (weight for age 61-70 per
      cent) and severe (weight < or = 60 per cent) malnutrition, and in children with
      marked linear growth retardation (height for age < 85 per cent). Nearly half of
      the marasmic children had serum magnesium levels in the hypomagnesemic range
      (below 1.56 mg/dl). Serum magnesium levels had significant correlations with
      height for age and serum albumin.

PMID- 9604604
TI  - Immunological response to primary and secondary measles vaccination among school
      age children in Malatya, Turkey.

PMID- 9604606
TI  - Clinical profile and Japanese encephalitis viral serological screening of
      children with acute encephalitis in Varanasi, India.

PMID- 9604605
TI  - Concentration of total serum IgE in parasitized children and the effects of the
      antiparasitic therapy on IgE levels.

PMID- 9604607
TI  - Neonatal purpura fulminans due to homozygous protein C deficiency.

PMID- 9604608
TI  - On the other hand.

PMID- 9604609
TI  - Values.

PMID- 9604610
TI  - The effect of a paraprofessional home visiting program on utilization of prenatal
      care.

PMID- 9604611
TI  - Incidence of acute appendicitis confirmed by histopathologic diagnosis.
AB  - The annual incidence of acute appendicitis by gender, age, and race in Sedgwick
      County, Kansas was lower than values reported in most other communities. However,
      the trends of peak incidence during the second decade, male predominance among
      all races, and the highest incidence in Caucasians also were noted in the current
      study. The rates of perforation and gangrenous appendicitis were significantly
      higher in the elderly. No association was noted between the presence of fecalith
      and acute appendicitis or perforation. A better understanding of the etiology of
      acute appendicitis may explain the trends and differences in the incidence of
      acute appendicitis observed.

PMID- 9604612
TI  - Patient visits to small rural emergency rooms.

PMID- 9604613
TI  - Insulinoma.

PMID- 9604614
TI  - Regionalization of trauma care: a necessity for Kansas.

PMID- 9604615
TI  - Serous cystadenofibroma arising in an ectopic ovary.

PMID- 9604616
TI  - Dealing with grown children of elderly patients.

PMID- 9604617
TI  - Thoughts on surgical practice in a rural setting.

PMID- 9604618
TI  - Oral rehydration therapy for pediatric gastroenteritis.

PMID- 9604619
TI  - KMS president's inaugural address.

PMID- 9604620
TI  - KMSA president's inaugural address.

PMID- 9604622
TI  - The physician in changing times.

PMID- 9604621
TI  - De-frauded?

PMID- 9604623
TI  - Coronary artery ectasia.
AB  - Coronary artery ectasia is an uncommon expression of coronary artery
      atherosclerosis and other diseases. It occurs in about 1.4 percent of the adult
      population. It is not distinguishable from obstructive coronary artery disease in
      severity of angina, clinical presentation, electrocardiograms, mortality, or
      outcome of coronary artery surgery. Although there is debate, treatment is
      indicated in the form of chronic warfarin anticoagulation to prevent coronary
      thrombus formation and its sequelae. Aspirin therapy may suffice in asymptomatic
      individuals.

PMID- 9604625
TI  - Splenosis: a report of ovarian stromal involvement.

PMID- 9604624
TI  - A multi-state outbreak of Salmonella serotypes Infantis and Anatum-Kansas and
      Missouri, 1997.

PMID- 9604626
TI  - Pulmonary ossification in association with congenital protein C deficiency.
AB  - A case of diffuse pulmonary ossification in association with congenital protein C
      deficiency is presented. We propose that multiple pulmonary thrombi secondary to
      a long-term hypercoagulable state produced pulmonary ischemia that predisposed to
      intralveolar ossification.

PMID- 9604627
TI  - A clinical approach to proper nutrition in the elderly.
AB  - Cost-effective evaluation and management of nutritional needs remains an ongoing
      challenge to those caring for older adults. Further elucidation of the factors
      that influence appetite and intake is needed, as is continuing research regarding
      the effects of various nutritional interventions upon clinically important
      outcomes.

PMID- 9604629
TI  - Mercury spills: an under-recognized hazard.

PMID- 9604630
TI  - [The best treatment in tinnitus: good advice and good psychological care].

PMID- 9604631
TI  - [New guidelines for treatment of neonatal asphyxia. Pure oxygen is not suitable,
      narrower time limits for resuscitation].

PMID- 9604632
TI  - [Internet, the information flow and the clinical everyday].

PMID- 9604633
TI  - [Genetic causes of schizophrenia are overemphasized].

PMID- 9604634
TI  - [Feared risk factors in connection with calcium antagonists are not to be
      dismissed].

PMID- 9604635
TI  - [Hippocrates' ethics--the interpretation was unfairly criticized].

PMID- 9604636
TI  - [Acupuncture worth trying in severe tinnitus].
AB  - The article consists in a report of a study of 22 patients with disabling
      tinnitus, performed to elucidate the effects of a 3-month course of acupuncture
      (15 treatments) on the severity of tinnitus and on quality of life (QOL), as
      compared with those of individualised physiotherapy. The study was designed as a
      prospective, randomised, cross-over study with a follow-up period of one year
      after the final treatment. Treatment effects were evaluated in terms of the
      patients' VAS (visual analogue scale) ratings and answers to questionnaires,
      including the NHP (Nottingham Health Profile), regarding the impact of tinnitus
      on different aspects of QOL. Baseline NHP scores showed tinnitus patients to
      manifest pronounced depressive characteristics. Acupuncture was found to yield
      immediate relief, both in terms of loudness and disturbance of the tinnitus, and
      significant improvement in QOL (NHP) for three months after the conclusion of
      treatment. Although many patients in the subgroup with concurrent muscle tension
      reported beneficial effects of individualised physiotherapy, such treatment
      yielded no significant reduction of tinnitus loudness or disturbance due to
      tinnitus, and no improvement in NHP scores. In both treatment groups, however,
      both annoyance due to tinnitus and QOL scores had returned to pretreatment levels
      at one-year follow-up. Thus, the results suggest tinnitus patients to manifest
      depressive characteristics, and that acupuncture may yield temporary improvement
      in terms of tinnitus relief and QOL.

PMID- 9604637
TI  - [An old instruction book for people with eating disorders].

PMID- 9604638
TI  - [Two sides of patients with eating disorders. One wants to get better, the other
      resists].
AB  - Anorexia and bulimia nervosa patients often require long-term treatment. The
      efficacy of different treatment approaches is insufficiently known, and for many
      years well-defined treatment goals were lacking. However, treatment studies are
      being published, or are under way. In this paper, the authors attempt to
      summarize the current state-of-knowledge in the field of eating disorder
      treatment.

PMID- 9604639
TI  - [More and more patients with more severe illnesses are being rehabilitated at
      home].

PMID- 9604640
TI  - [Newly discovered estrogen receptor. New therapeutic possibilities in
      postmenopausal symptoms, osteoporosis, cancer of the breast and prostate].
AB  - A previously unknown oestrogen receptor, ER beta, has recently been isolated. ER
      beta is expressed in many important target tissues for oestrogen (i.e., prostate,
      ovary, testis, and the cardiovascular and central nervous systems), and probably
      mediates many of the effects of oestrogens in the human body. Moreover, ER beta
      represents an interesting target for drug development, and ligands specific for
      the respective receptor subtype may offer interesting possibilities for the
      treatment of postmenopausal symptoms, and breast and prostate cancer, without
      many of the hitherto adverse side effects, such as the increased risk of
      endometrial cancer associated with hormone replacement therapy.

PMID- 9604641
TI  - [Factors affecting health of immigrant and refugee children].

PMID- 9604642
TI  - [Trauma and vulnerability among children. New knowledge necessitates conceptual
      revision].
AB  - How are we to understand a child's development--both the potentiating and
      inhibiting factors? The past two decades have witnessed intensive research both
      on mental trauma and its possible effects on the child's developing brain, and on
      the importance of risk factors and protective factors in children's development
      and health. Research in these two fields has been conducted concurrently and has
      yielded new, important, and in many cases complementary, information. To promote
      the general availability and clinical applicability of these advances in our
      knowledge, it is necessary to modify our conceptual approach, basing it on the
      child's perspective instead.

PMID- 9604643
TI  - [Estonian ambulances--Dr. Finlay with a blue light].

PMID- 9604645
TI  - Is ignorance bliss? Could jury trial survive investigation?

PMID- 9604644
TI  - The effectiveness of juries and the use of the civil courts in the control of
      crime--the emperor's new clothes?

PMID- 9604646
TI  - The case for jury research.

PMID- 9604647
TI  - Trying criminal cases without juries.

PMID- 9604648
TI  - Leave the jury alone.

PMID- 9604649
TI  - Remedying harm: civil and criminal justice.

PMID- 9604650
TI  - 'Community safety': the use of civil courts by local authorities and the police
      to control criminal behaviour.

PMID- 9604651
TI  - Involuntary disclosure of private medical records to the defence in criminal
      proceedings.
AB  - This article concerns the law and procedure governing the production and
      disclosure to an accused of medical and therapeutic records in the hands of third
      parties, not part of the Crown's case against the accused. Following a brief
      analysis of the medico-legal issues involved, this article examines recent
      statutory changes regarding involuntary disclosure to an accused by third parties
      of private records in their possession.

PMID- 9604652
TI  - Return to special: an examination of the characteristics of patients who returned
      to Ashworth special hospital.
AB  - Sixteen patients were returned to Ashworth in a one-year period (five second
      admissions, 10 failed leave of absence and one warrant of recall) making up 31%
      of admissions for the year. Demographic details and reasons for return were
      collected. Fifty per cent of patients had a clinical diagnosis of personality
      disorder. Reasons for return included relapse of psychosis, persistent
      transgression of boundaries, aggression or threatened aggression, unsuitable
      placements and failure to progress towards discharge.

PMID- 9604653
TI  - An analysis of a recent criminal trial involving sexual misconduct with a child,
      alcohol abuse and a successful sleepwalking defence: arguments supporting two
      proposed new forensic categories.
AB  - The final judgment from a recent criminal trial in the British Columbia (Canada)
      Supreme Court is summarized and discussed. The trial involved sexual misconduct
      with a child, excessive alcohol use, and a successful 'sleepwalking (SW) defence'
      (non-insane automatism). Our comments on this trial provide an opportunity to
      present our arguments buttressing two newly proposed forensic categories: (i)
      parasomnia with continuing danger as a non-insane automatism, which originally
      was proposed for cases involving recurrent, sleep-related violence, but which can
      also be applied to SW cases involving sleep-related sexual misconduct and alcohol
      abuse (and other high-risk self-abusive behaviours); (ii) (intermittent) state
      dependent continuing danger, an intermediate category within the 'continuing
      danger' concept, with the core feature being that a person acquitted of a
      criminal charge on the basis of the 'SW defence' (or some other parasomnia
      defence), in which the SW episode was provoked by a high-risk behaviour (e.g.
      alcohol intoxication) should bear full legal culpability for any future episode
      that was provoked by a recurrence of the high-risk behaviour--provided that the
      individual had wilfully engaged in that behaviour.

PMID- 9604654
TI  - Dowry death: implications of law.
AB  - The giving of dowry on marriage is a widespread custom in India, but the attitude
      of society towards this practice is neither uniform nor consistent. 'Dowry death'
      is the result of a unique form of violence suffered by Indian women. The existing
      legal provisions relating to dowry and dowry deaths are summarized, and the role
      of the Indian Penal Code is discussed. Case reports are presented.

PMID- 9604655
TI  - Reproducibility of within-subject breath alcohol analysis.
AB  - Random samples from normal distributions are an important assumption for many
      statistical methods. The present study evaluates this assumption with regard to
      quantitative breath alcohol analyses. Eight individuals (six male and two female)
      consumed alcoholic beverages and subsequently provided replicate (n ranging from
      22 to 69) breath samples to an infrared breath alcohol instrument within short
      time intervals. The serially collected data were treated with several descriptive
      and inferential methods. Descriptive results among the eight individuals
      included: mean 0.0420-0.1175 g/210 L, SD 0.0008-0.0045 g/210 L and CV: 1.9%-4.7%.
      Statistical tests for normality showed seven of the distributions to be
      reasonably normal (p > or = 0.25) and the other marginal (p = 0.051). A test for
      runs about the median showed random results (p > or = 0.10) for four individuals
      and non-random (p < or = 0.01) for the other four. The results suggest an
      individual's breath alcohol measurement, when appropriately collected and
      analysed, should be considered a random sample from a normal within-subject
      distribution. The existing variability in breath alcohol analysis, due largely to
      biological and sampling considerations, is acceptably minimized to warrant
      forensic application.

PMID- 9604656
TI  - The Intoximeter 3000 and the four minute fallacy.
AB  - Claims that breath alcohol values measured on the Lion Intoximeter 3000 are
      invalid if the machine clock is incorrect by more than four minutes have been
      shown to be technically incorrect. A study involving measurement of simulated
      breath alcohol levels with various Intoximeter 3000 clock times shows no
      variation within normal tolerances for breath alcohol values.

PMID- 9604657
TI  - The khat users: a study of khat chewing in Liverpool's Somali men.
AB  - This study reports the demographic and social characteristics and level of
      psychological dysfunction in regular khat users compared with matched non-users.
      The results indicate that khat users resemble non-users on a number of
      psychosocial variables and GHQ scores, with no evidence to suggest higher
      morbidity amongst users. The two groups appear to differ only in the level of
      their use of nicotine and also in their perception of the harmful effects
      associated with khat use.

PMID- 9604658
TI  - Exploration of a Durkheimian theory of suicide and homicide in Australia and New
      Zealand.
AB  - A time-series study of suicide and homicide rates in Australia and New Zealand
      from 1950-85 provided limited support for Durkheim's theory of suicide and no
      support for Henry and Short's theory of the relationship between suicide and
      homicide. The need for rival theories is discussed.

PMID- 9604659
TI  - Non-accidental injury inflicted on a child with an air weapon.
AB  - A case of non-accidental injury to an infant caused by the discharge of an air
      pistol is presented, the first such case to be reported. A two-month-old baby was
      shot at close range by his father with a .177 air pistol. A false account of the
      cause of the injury was given by the father and initially supported by the
      mother. The pellet penetrated the skin in the centre of the child's forehead and
      lodged in the anterior wall of the sagittal sinus. It was removed under general
      anaesthetic and the child made an uncomplicated recovery. The father was
      subsequently convicted and jailed for the assault. The relevant literature on air
      weapon injuries and bizarre forms of child abuse is discussed.

PMID- 9604660
TI  - Sudden death in a child due to rare endocranial neoformation.
AB  - A case of unexpected death in a six-year-old child, who died after a period of
      non-specific symptoms and clinical signs, is described. The cause of death was a
      pilocytic astrocytoma of the pontocerebellar angle, rare with regard to location
      and histology. The authors have reviewed the literature, which was scanty.

PMID- 9604662
TI  - Getting from 16 to 17.

PMID- 9604663
TI  - Medicare identifies claim denials.

PMID- 9604661
TI  - Self-inflicted bite injuries associated with intracerebral haemorrhages.
AB  - A case of self-inflicted bite injuries of the fingers with an episode of small
      intracerebral haemorrhages is presented. There were many injuries on the right
      fingers. The tip of the right forefinger was bitten off, and some small pieces of
      the finger had been aspirated and swallowed. This unusual case seemed to be an
      emotional response to pain from cerebral episode.

PMID- 9604664
TI  - The peer review privilege: what documents are protected from discovery in
      litigation.

PMID- 9604665
TI  - Recent developments in electronic medical records.
AB  - Human factors engineering principles will guide the development of future EMR
      systems. Physicians will use wireless palmtop computers to record patient data so
      that the computer does not come between the physician and patient in routine
      encounters. With few exceptions, the pieces for this type of system are available
      today, but not in one package. I believe EMR developers have recognized the
      ubiquity and power of the Internet. Because of advances in computers, software,
      and telecommunications reliability, solutions using thin-client technology will
      lower the cost of EMRs to physicians.

PMID- 9604666
TI  - Radiology quiz #17. Pneumoperitoneum.

PMID- 9604667
TI  - Arterial vascular remodeling: the endothelial cell's central role.
AB  - Atherosclerosis is a focal chronic inflammatory fibroproliferative disease of the
      arterial intima caused by the retention of modified low density lipoproteins and
      hemodynamic stress. Paradoxically, this inflammatory fibroproliferative complex
      process of repair and healing can become destructive resulting in the remodeling
      of the arterial vessel wall creating lumen narrowing and ischemia to the involved
      tissues and organs. In this paper the central role of the endothelial cell is
      discussed and it is demonstrated how the remodeling within the intima can lead to
      plaque rupture and thrombosis with arterial occlusion. The role of the injurious
      stimuli, the response of the endothelial cell, and the adaptive changes within
      the intima are discussed in relation to arterial vascular remodeling. Intimal
      vessel wall remodeling and its relation to the development, progression, and
      final fate of the atherosclerotic plaque cannot be overemphasized.

PMID- 9604668
TI  - Gender differences in depressive symptoms among Spanish elderly.
AB  - The aim of this study is to describe gender differences in depressive
      symptomatology among an elderly Spanish population and to see whether women are
      more at risk than men and whether the effects of known risk factors for
      depression differ between the genders. Data come from the study Envejecer en
      Leganes (Growing Old in Leganes), where a representative sample of community
      residing elderly was screened by an at-home interview for high depressive
      symptomatology using the Center for Epidemiologic Studies Depression Scale (CES
      D). Sociodemographic characteristics, health status, Activities of Daily Living
      and Instrumental Activities of Daily Living, disability, social support, and
      locus of control were measured as possible correlates of depressive symptoms.
      Screening was completed in 1116 subjects. The prevalence of high depressive
      symptomatology varied, being 19.6% for men and 46% for women (OR = 3.4; 95% CI =
      2.6; 4.5). In addition to gender, comorbidity, low emotional support from
      children, lack of a confidant, few social activities, and a sense of lack of
      control were independently associated with high levels of depressive symptoms.
      None of the interactions of gender by the known risk factors of depression was
      significant. Although the prevalence of depressive symptomatology is higher in
      women than in men, the known risk factors do not totally explain the difference
      between genders in this population of Spanish elderly. This difference could be
      due to the cultural definitions of gender roles that have affected them
      throughout their lives.

PMID- 9604669
TI  - The association of psychiatric diagnosis with weather conditions in a large urban
      homeless sample.
AB  - Assessment of psychiatric disorders encounters unique complexities in homeless
      populations. Although the use of structured diagnostic instruments has
      significantly improved research methodology in this area, questions remain about
      the validity of using cross-sectional diagnostic methods derived from studies of
      more general populations. In particular, the validity of structured diagnostic
      instruments in the assessment of schizophrenia, depression, drug use disorder,
      and antisocial personality disorder (ASPD) in homeless populations has been
      questioned. The purpose of this study was to examine the association of
      psychiatric diagnoses with the weather. It was hypothesized that self-report of
      psychiatric illness may be affected by prevailing weather conditions. Nine
      hundred homeless subjects randomly sampled from St. Louis shelters, day centers,
      and unsheltered locations were interviewed over a 1-year period. Official average
      daily temperature and amount of precipitation on the day of each subject's
      interview were compared with lifetime and current psychiatric diagnoses
      ascertained by the Diagnostic Interview Schedule. Similar analyses were performed
      in general population data from the Epidemiologic Catchment Area study. The study
      found that among homeless men, inclement weather on the day of interview was
      associated with lifetime and current diagnoses of major depression, lifetime drug
      use disorder, lifetime diagnosis of ASPD, and current alcohol use disorder. These
      findings, however, were not present in homeless women and not reflected in the
      general population. The results, although limited, suggest that weather may
      confound cross-sectional, standardized methods of psychiatric diagnosis in
      homeless men. Weather-related factors among homeless men are associated with
      ascertainment of both lifetime and current diagnosis of major depression, as well
      as lifetime drug use disorder and ASPD and current alcohol use disorder. Possible
      interpretations of these findings are discussed, with implications for
      intervention strategies for psychiatric disorders in the larger context of
      homelessness and social problems.

PMID- 9604670
TI  - Seasonal variations in hospital admissions for affective disorders by gender and
      ethnicity.
AB  - Hospital admission statistics for depression and mania have shown significant
      seasonal patterns. The present investigation was conducted to establish the
      pervasiveness of the impact of seasons on mood disorder presentation at
      Birmingham (52 degrees North) by gender and ethnicity. Non-mood disorder
      admissions were examined as a control to determine the specificity of any
      seasonal variation to affective illness. Case notes for 992 admissions, during
      January-December 1995 inclusive, to an inpatient unit were reviewed
      retrospectively. Admission data were broken down by gender and into three ethnic
      groups: Asian, white and black. Seasonality in admissions for depression, bipolar
      disorder and non-mood disorders was tested by gender and ethnicity. Admission
      frequencies for depression showed significant seasonal pattern, with the
      incidence of depression being highest in winter. Total admissions, bipolar and
      non-mood disorders did not show any significant seasonal variability. A gender
      effect was evident on seasonality of admissions for affective illness, with
      significant winter peak for depression and summer peak for bipolar disorder in
      women only. The Asian group was the only ethnic group that showed significant
      seasonal variation in depression, with a greater number of depressive episodes in
      winter. Environmental variables were related significantly to the incidence of
      mood disorders. Specific seasonal effect for affective illness was evidenced by
      the non-existence of seasonality in other psychiatric disorders. The reverse
      seasonal pattern for depression and mania suggests a maladaptive response of
      vulnerable individuals to specific functions of seasons.

PMID- 9604671
TI  - Patterns of psychiatric hospital service use in Finland: a national register
      study of hospital discharges in the early 1990s.
AB  - We were interested in studying the possible concurrent changes in the psychiatric
      inpatient population during a rapid phase of deinstitutionalisation, and severe
      economic recession with a record level unemployment rate, and after the amendment
      of the mental health legislation. Although there were 4540 fewer beds in the
      psychiatric hospitals in 1993 compared to 1990, the rate of patient admissions
      remained the same. There was a significant increase in readmissions (P < 0.001)
      to the psychiatric hospitals, and particularly in multiple (three or more)
      readmissions among new inpatients (P < 0.001). The prevalence of inpatients with
      major depression increased by 0.2/1000 in the whole cohort and by 0.12/1000 among
      first-timers from 1990 to 1993 (P < 0.001). In addition, the rate of involuntary
      admissions decreased significantly (P < 0.001).

PMID- 9604672
TI  - Mortality among psychiatric patients referred to the mental health services in
      Valencia.
AB  - The rate of survival and causes of mortality in a cohort of 2103 psychiatric
      patients registered on a psychiatric case register and followed up for 7 years
      are compared with those of a general population sample (n = 2382) randomly
      extracted from the municipal census in Valencia (Spain). Using multivariate
      analysis by Cox regression, patients suffering organic psychoses and those
      diagnosed with drug abuse or dependency exhibited a greater risk of death than
      the general population for the total causes of death; no interaction was found
      between sociodemographic variables and psychiatric pathology. In terms of the
      causes of death, and controlling for the effect of age and sex, organic psychoses
      involved a greater risk of death due to cardiovascular and respiratory causes,
      and a greater risk of non-natural deaths than the general population.
      Schizophrenia and related conditions, the abuse of alcohol/ other drugs, and
      neurosis/personality disorders all presented a higher risk of death from liver
      disease. The major affective disorders involved a greater risk of death due to
      suicide or accidents. The study concludes with a discussion of the possible
      explanations of these results.

PMID- 9604673
TI  - HIV infection and suicide risk: an epidemiological inquiry among male homosexuals
      in Switzerland.
AB  - Conflicting results have been published about suicidality among HIV+ subjects;
      part of the alleged increased risk may be linked to premorbid risk factors such
      as drug addiction and homosexuality. In order to cope with these confounding
      factors, we assessed the degree of suicidal ideation in a sample of Swiss male
      homo- and bisexuals, comparing HIV- and HIV+ subjects. A total of 164 subjects
      returned a self-administered, home-completed questionnaire, which had been
      circulated among homosexuals in the French speaking part of Switzerland. Suicidal
      ideation was assessed through Poldinger's scale. Serostatus was known for 149
      subjects, among whom 65 were HIV+. A high rate of suicide attempts was found
      among homosexuals, both HIV- and HIV+. Scores on Poldinger's scale are
      significantly, though moderately, higher among HIV+ subjects, and this finding
      seems to be a direct consequence of HIV infection.

PMID- 9604674
TI  - Risk factors for suicidal ideation in psychiatric patients.
AB  - Sociodemographic and clinical risk factors for suicidal ideation have been less
      studied than risk factors for parasuicide and suicide. No reports on associations
      between therapy satisfaction and suicidal ideation among psychiatric patients
      have been published. In this study we compared a group of patients with suicidal
      ideation (n = 84) with a randomly selected group of nonsuicidal patients (n =
      166) in community-based psychiatric services. Patients with suicidal ideation
      felt a need for psychiatric treatment more often than nonsuicidal patients. They
      were also more likely to receive antidepressive medication, and weekly therapy
      sessions were more common among them. A wish to change therapist (OR 15.6, 95% CI
      3.6-67.8), hopeless future orientation (OR 14.8, 95% CI 4.5-48.9), severe
      depression as evaluated by the Beck Depression Inventory (OR 14.0, 95% CI 4.3
      45.2) and dysthymia (OR 12.8, 95% CI 1.7-97.3) were the factors most strongly
      associated with suicidal ideation in multivariate analysis. A wish to change
      therapist is an expression of therapy dissatisfaction, which may therefore be
      among the factors most strongly associated with suicidal ideation in psychiatric
      patients. To help prevent suicidality among psychiatric patients special
      attention to therapy factors is needed.

PMID- 9604675
TI  - [Laparoscopic cholecystectomy as an ambulatory intervention?].

PMID- 9604676
TI  - [Here are we now--status after 25 years].

PMID- 9604677
TI  - [Determination of the expected day of delivery--ultrasound has not been shown to
      be more accurate than the calendar method].
AB  - It has been claimed that the expected day of delivery (EDD) determined on the
      basis of an ultrasound scan is more accurate than using a calendar method. The
      aim of this paper is to assess the evidence in support of this claim. A critical
      review of the methodologically best research revealed that among women with
      regular cycles and know first day of the last menstrual period, Naegele's rule
      predicted the EDD to be 3.3 days too early, on average, whereas prediction based
      on ultrasound scans was 2.0 days too late. The standard deviations of the two
      distributions were the same. After correction for the systematic biases, the two
      methods of prediction were thus equally precise. It is concluded that the EDD
      should be calculated by adding 283 days to the date of the last period rather
      than by adding 280 days. For women with regular cycles and known first day of the
      last menstrual period, ultrasound dating does not lead to a more precise
      prediction.

PMID- 9604678
TI  - [Treatment of primary low-grade gastric lymphomas with eradication of
      Helicobacter pylori].
AB  - There is evidence associating Helicobacter pylori (HP) with both mulosa
      associated lymphoid tissue (MALT) and MALT-lymphoma. Recently, three studies
      including 65 patients have shown that the eradication of HP can lead to
      regression in about 60-70% of primary low-grade gastric B-cell MALT-lymphomas.
      Prolonged follow-up will be necessary to see whether these remissions are
      lasting, and whether eradication of HP in combination with conventional therapy
      is more effective than either of these treatments alone. Until then we recommend
      that HP is eradicated in these lymphomas before referral to standard treatment
      with chemotherapy and/or radiotherapy.

PMID- 9604679
TI  - [Ambulatory laparoscopic cholecystectomy. Feasibility and convalescence].
AB  - The purpose was to describe feasibility of and convalescence after laparoscopic
      cholecystectomy in a day case set up in this prospective, open, and descriptive
      study. Fifty consecutive patients referred for elective cholecystectomy
      participated. An overnight stay was planned for 13 patients, (12 because they
      lived alone, one because of pulmonary disease ASA III). The operation was in all
      cases performed under combined epidural-general anaesthesia. The primary issues
      were duration of hospital stay, reasons for delayed discharge, frequencies of
      nausea and vomiting, as well as duration of convalescence and reasons for
      postponement of return to work or recreational activities. Twenty-six patients
      (of 37 candidates for day case surgery) were discharged on the day of surgery and
      16 on the first postoperative day. Eleven patients had nausea, and three vomited
      during the first three postoperative hours. Pain was the most common contributory
      reason for overnight stay (17 patients, eight of these being planned day-case
      patients who stayed overnight). The patients were recommended to resume work and
      recreational activities after 48 hours, but 35 patients did not observe this
      recommendation. The median number of days off work or recreational activity was
      four days (2-8), including the day of surgery. Pain was the most common
      contributory reason (19 patients). CONCLUSIONS: Laparoscopic cholecystectomy can
      be performed as an outpatient operation in more than half of all patients, in
      approximately 70% of patients not living alone, and with only 15% of the patients
      requiring more than one over-night stay. Postoperative pain is the primary reason
      for both delayed discharge and prolonged convalescence. Up to one week's duration
      of convalescence is recommended.

PMID- 9604680
TI  - [Incidence and prevalence of symptomatic celiac disease among adults in Denmark].
AB  - The purpose was: 1) to determine annual incidence rates of adult coeliac disease,
      2) to calculate the risk of having developed coeliac disease in adult life, and
      3) to calculate the life time prevalence by five-year birth cohorts. All patients
      fulfilling defined criteria for adult coeliac disease living in the county of
      Copenhagen and diagnosed during the years 1976-1991 were included. The reference
      population consisted of 503,283 subjects. The overall incidence had been stable
      during the period, and was 1.27/10(5). The figures for females and males were
      1.55/10(5) and 0.96/10(5), respectively (p = 0.04). The median (range) age at the
      time of diagnosis was 40.1 (16-81). Age specific incidence rates varied
      considerably, with the peak rate located in the middle-aged population. The
      incidence rates were influenced by age at diagnosis (p = 0.01) and sex (p =
      0.04), but not by the year when diagnosed. For a subject aged 89 years, the risk
      was 0.88/1000. The overall prevalence was 45.9/10(5). In conclusion, this
      incidence/prevalence is one of the lowest reported, and is definitely lower than
      prevalences reported from our neighbouring Scandinavian countries. Nothing points
      to higher incidence rates being present in Danish adults to compensate for the
      previously demonstrated very low rates in Danish children.

PMID- 9604682
TI  - [Helicobacter pylori infection and socioeconomic factors among adult Danes].
AB  - The aim of this study was to examine the relationship between housing conditions,
      educational level, occupational factors, and serologically diagnosed acute and
      chronic Helicobacter pylori infection. IgG, IgM, and IgA antibodies against
      Helicobacter pylori were measured by ELISA techniques in sera obtained from a
      random sample of 3589 Danes participating in a population study. Poor social
      status (odds ratio 2.2 [1.7-3.0]), short duration of schooling (odds ratio 2.0
      [1.3-2.5]), lack of vocational training/education (odds ratio 1.4 [1.2-1.7]),
      unskilled work (odds ratio 1.7 [1.2-2.5]), and high work-related energy
      expenditure (odds ratio 1.4 [1.1-1.9]) increased the likelihood of chronic
      Helicobacter pylori infection. Chronic Helicobacter pylori infection was
      frequently found in people with a history of living abroad. Increased levels
      solely of IgM antibodies to H. pylori, interpreted as a sign of acute infection,
      were found more often in people who were divorced (odds ratio 2.3 [1.2-4.4]) or
      unmarried (odds ratio 2.0 [1.1-3.8]) and in people who worked long hours (odds
      ratio 2.0 [1.1-4.0]). In conclusion, educational and occupational factors relate
      to the likelihood of chronic Helicobacter pylori infection in adults. The rate of
      acute Helicobacter pylori infection is probably increased in single adults.

PMID- 9604681
TI  - [Pediatric colonoscopy].
AB  - The procedure and results of 50 colonoscopies performed over a three-year period
      on a group of 43 children (range: 0.3-16 yr; median: 9 yr) are described. The
      main indications were evaluation for, or control of already known, chronic
      inflammatory bowel disease (n = 38) and rectal bleeding (n = 8). Following verbal
      and written information the children were admitted one to two days before the
      procedure for bowel preparation. Children < 10 years old received general
      anaesthesia during the colonoscopy (n = 25) and most children > or = 10 years old
      received an intravenous sedation with pethidine and midazolam (n = 25). In only
      one case was intravenous sedation not successful. The coecum was visualised in
      96% and the terminal ileum intubated in 77% (when intended) of the endoscopies.
      The most important results obtained were establishment of the diagnosis of
      inflammatory bowel disease in 21 of 30 suspected cases and the removal of a polyp
      in two cases. At the time of colonoscopy a "best guess" diagnosis of either
      ulcerative colitis or Crohn's disease often predicted the histological diagnosis,
      but endoscopy tended to underestimate the severity and extent of the inflammation
      as compared to microscopy. There were no complications. We conclude that
      colonoscopy performed according to our recommendations is a safe and informative
      procedure for evaluation of the large bowel and terminal ileum in children with
      intestinal disease.

PMID- 9604683
TI  - [Pulmonary vasculitis as an extraintestinal manifestation in ulcerative
      coliltis].
AB  - Pulmonary complications are rarely reported in association with ulcerative
      colitis. Our patient had ulcerative colitis, diagnosed three decades earlier.
      Following a relapse of his ulcerative colitis, the patient developed bloodstained
      sputum. Chest CT-scan showed signs of pulmonary tissue infiltration indicating
      pulmonary vasculitis. No causative agent for this clinical condition was found.
      Testing for ANCA showed the vasculitis to most likely be secondary to his
      ulcerative colitis. The lung lesions responded to corticosteroid therapy within a
      week, and the following chest CT-scan was normal.

PMID- 9604684
TI  - [A new therapeutic strategy in sore throat?].

PMID- 9604685
TI  - [Gene manipulated food--a health hazard?].

PMID- 9604686
TI  - [The status article on arterial and venous diagnostics published in the Ugeskrift
      for Laeger 1997; 159: 7293-301].

PMID- 9604687
TI  - [Mivacurium. A non-depolarizing neuromuscular blocking agent with short-lasting
      effect].

PMID- 9604688
TI  - [Pulmonary adverse effects caused by salazosulfapyridine].

PMID- 9604689
TI  - Injury visits to hospital emergency departments: United States, 1992-95.
AB  - OBJECTIVES: This report describes ambulatory care visits for injuries to hospital
      emergency departments in the United States. Statistics are presented on selected
      patient, hospital, and visit characteristics. METHODS: The data presented in this
      report were collected in the National Hospital Ambulatory Medical Care Survey
      (NHAMCS) over a period of 4 years from 1992 through 1995. The NHAMCS is a
      national probability survey of visits to hospital emergency and outpatient
      departments of non-Federal, short-stay, and general hospitals in the United
      States. Sample data were combined across years and weighted to produce annual
      estimates. RESULTS: From 1992 through 1995, an estimated 147 million visits for
      injuries were made to hospital emergency departments in the United States, an
      average of 36.8 million visits per year with an annual utilization rate of 14.3
      visits per 100 persons. Persons 15-24 years had a higher rate of injury-related
      emergency department visits compared with other age groups. The injury visit rate
      was higher in the Midwest than in the South or West. Injury visits represented
      37.8 percent of all visits to hospital emergency departments but 53.5 percent of
      all visits for children between 5 and 14 years and 48.5 percent of all visits for
      persons 15-24 years. Open wounds accounted for the largest proportion of injuries
      (22.0 percent). The leading external causes of injuries included falls, being
      struck by or striking against a person or object, and motor vehicle traffic
      injuries. For all ages, 6.3 percent of the injury visits had a disposition of
      admission for inpatient care, while almost one-quarter of injury visits by
      persons 65 years and over resulted in hospitalization. ED visits caused by
      poisonings or firearm injuries were more likely to result in hospitalization
      compared with other causes.

PMID- 9604690
TI  - Studies of the effect of physical and chemical interactions of cellulose ethers
      and sulfonamides in tablets on the drug release.
AB  - The paper reports results of the studies of sulfonamide tablets obtained by the
      incorporation in hydrophilic carrier (Cellulose ether). The rate of sulfonamide
      release was determined by the paddle method. The occurrence of physical and
      chemical interactions of sulfonamides and cellulose ethers in the solid phase was
      confirmed by X-ray diffraction and thermal (TG and DSC) studies. The influence of
      these interactions on the sulfonamide release from the tablets was analyzed.

PMID- 9604691
TI  - Adaptation of the cytokinesis-block technique for genotoxicity assay on L929 cell
      line.
AB  - The in vitro micronucleus assay was used as a method for evaluation of
      chromosomal damage in L929 cells. Known genotoxins were used to induce
      micronuclei: bleomycin the direct acting agent, and cyclophosphamide the
      substance which requires metabolic activation. The cytokinesis-block technique
      and the use of exogenous metabolizing system is precisely described.

PMID- 9604692
TI  - The in vitro study on genotoxic activity of adriamycin and bleomycin in cells of
      mice with different catalase and superoxide dismutase activity.
AB  - Genotoxic activity of adriamycin and bleomycin in embryo cells from mice
      differing in anti-oxidant enzymes activity was investigated. The catalase
      activity in cultured in vitro embryo cells of C3H mice was 2.3-fold and
      superoxide dismutase 2.5-fold higher than of C57BL/10 mice. For genotoxicity
      evaluation, the micronucleus test in vitro was used. The results obtained
      indicated that the frequency of micronucleated cells in untreated C3H cultures
      was higher than in C57BL/10 cell cultures. The increase in micronuclei formation
      after treatment with adriamycin and bleomycin was higher in C57BL/10 than in C3H
      cells as compared with micronuclei in untreated cultures. The higher frequency of
      micronucleated cells in treated versus untreated C57BL/10 than C3H cell cultures
      may be caused by lower activity of anti-oxidant enzymes in C57BL/10 cells. It may
      suggest that DNA damage caused by adriamycin and bleomycin resulted from action
      of active oxygen species.

PMID- 9604693
TI  - Induction of cytochromes P4502B1/2B2 by some antiepileptic drugs in rat liver.
AB  - The effects of phenobarbital (PB), carbamazepine (CBZ) and diazepam (DZ) on total
      hepatic cytochrome P450, cytochromes P4502B1/2B2 contents and aminopyrine N
      demethylase activity was investigated. Adult male rats were treated per os with
      PB (80 mg/kg/day), CBZ (75 mg/kg/day) or DZ (90 mg/kg/day) for 3 consecutives
      days. Carbamazepine and phenobarbital produced significant increase of the
      contents of total cytochrome P450 and cytochromes P4502B1/2B2 as well as
      aminopyrine N-demethylase activity. In contrast, diazepam decreased the total
      hepatic cytochrome P450 content. This drug did not affect the level of
      cytochromes P4502B1/2B2 but increased aminopyrine N-demethylase activity
      comparing to the control animals.

PMID- 9604694
TI  - Effect of carbamazepine on cytochromes P4502B 1/2B2 in rats exposed to high
      environmental temperature.
AB  - The combined effect of carbamazepine (CBZ) and raised environmental temperature
      on total hepatic cytochrome P450 and on cytochromes P4502B1/2B2 contents was
      investigated. Carbamazepine produced significant increase of the contents of
      total cytochrome P450 and cytochromes P4502B1/2B2 in rats exposed to 21 degrees C
      and 28 degrees C. In contrast exposure of rats of 35 degrees C decreased
      induction capacity of carbamazepine.

PMID- 9604695
TI  - Syntheses of some new 4-chloro-2-mercapto-N(4H-1,2,4-triazol-3-yl)
      benzenesulphonamide with potential anticancer or anti-HIV activity.
AB  - 4-Chloro-2-mercapto-5-R1-N-(4-R2-4H-1,2,4-triazol-3-yl) benzenesulphonamide [VIII
      XIV] were prepared from the corresponding 4-chloro-3(R2-amino)-5-R1-1,1-dioxo
      1,4, 2-benzodithiazines [I-VII] then compd. [VIII-X] were S-carboxyalkylated to
      the corresponding 2-?5-chloro-4-methyl-2-[4-R2-4H-1,2,4-triazol-3-yl)aminosulphon
      yl] phenylthio?alkanoic acids [XVII-XXVI]. Preliminary screening of anti HIV-1
      and anticancer activity of compd. [XI,XII,XVII] was conducted.

PMID- 9604696
TI  - Synthesis of new N-substituted benzodiazepine derivatives with potential
      anxiolytic activity.
AB  - In continuation of the development of antipsychotic and anxiolytic agents with a
      reduced propensity toward extrapyramidal side-effects, a series of N-aminoalkyl
      derivatives of (s)-(+)-2,3-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11
      (10H, 11aH)-dione was prepared. Evaluation of these compounds in revealed a very
      low affinity for 5-HT1A receptor.

PMID- 9604697
TI  - Clinical gait analysis in biomechanics.

PMID- 9604698
TI  - Prevention through postural energization of spinal structures; treatment through
      percutaneous discectomy.

PMID- 9604699
TI  - European standards for wheelchairs. Complying with the medical devices directive.

PMID- 9604700
TI  - A new tool for minor-access surgery.

PMID- 9604701
TI  - Augmented reality systems for medical applications.

PMID- 9604702
TI  - Noninvasively measuring blood glucose using saliva.

PMID- 9604703
TI  - Exploring in vivo blood flow dynamics.

PMID- 9604704
TI  - Compression of skin tumor images.

PMID- 9604705
TI  - Automation of colonoscopy. Part II: Visual-control aspects.

PMID- 9604706
TI  - Estimating regularity in epileptic seizure time-series data. A complexity-measure
      approach.

PMID- 9604707
TI  - Studying the mechanics of left ventricular contraction.
AB  - Several interesting aspects of the ESPVR have been discussed in this study,
      including: a) A possibility to introduce, in an explicit manner, the active force
      of the myocardium in the formalism describing the PVR of the left ventricle. b) A
      possibility to express the ventriculo-arterial coupling by using the ratio
      Emax/eam in a way to distinguish between the normal physiological state and the
      mildly or severely depressed state of the heart. The possibility of also
      expressing this coupling by using directly different areas under ESPVR has been
      indicated. A third method, not discussed here, is to use the windkessel model
      (see [27, 53]). c) The relationship between oxygen consumption and all the areas
      under ESPVR. d) A possible mechanism of adaptation to short- or long-term
      variation in load condition by changing ESPVR in a way to create an SWR (see Fig.
      4 and Table 2). e) A possibility to use different areas under ESPVR for clinical
      diagnostic purposes (see [20]); an example for SWR and SWR/SW is given in Table.
      2. f) A possibility of noninvasive clinical application of various results of
      this study. Item (f) depends on the possibility of noninvasive measurement of the
      left ventricular pressure, which has been reported by Bourguignon and Wagner
      [61], and Sato, et al. [62]. Noninvasive measurement of left ventricular
      dimensions has been discussed by Teichholz, et al. [63], Grassman, et al. [64],
      Dumesnil et al [65], Dumesnil and Shoucri [66, 67]. Measurement of ESPVR from one
      loop of the contraction cycle has also been discussed by Takeuchi, et al. [68]
      and Nakamoto, et al. [69]. Further readings can be found in [70] and [71]. The
      list of references is not exhaustive, but has been chosen to illustrate various
      related aspects of the topics discussed.

PMID- 9604708
TI  - Electrothermally-assisted capsular shift.
AB  - The marriage of biomedical instrumentation and patient care has once again proven
      itself successful. The ETAC is a new procedure with various potential
      applications. Despite its embryonic stage, this procedure is being used by a
      handful of shoulder surgeons who are cautiously pursuing new and improved ways to
      prevent the common and debilitating diagnosis of shoulder instability. Follow-up
      thus far is short, and the current literature lacks studies that compare the time
      honored conventional standard of open stabilization to this new procedure.
      However, those surgeons who have been using this device are optimistic about its
      role in the future repair of shoulder injuries.

PMID- 9604709
TI  - An inexpensive light source for oncologic photodynamic therapy.

PMID- 9604710
TI  - How did Georg Simon Ohm do it?

PMID- 9604711
TI  - Radiofrequency interference with medical devices. A technical information
      statement.
AB  - The past few years have seen increased reports that medical devices, such as
      pacemakers, apnea monitors, electrically powered wheelchairs, etc., have failed
      to operate correctly because of interference from various emitters of
      radiofrequency energy. This condition is called radiofrequency interference
      (RFI). The consequences of these failures range from inconvenience to serious
      injuries and death. Reasons for this problem are twofold: 1) increasing numbers
      of electronically controlled medical devices with inadequate electronic
      protection against RFI, and 2) a significant increase in the number of RF sources
      in the environment. Medical devices are widely used outside the hospital and may
      be attached to, or implanted in, patients. Portable wireless communications
      equipment, including cellular phones, handheld transceivers, and vehicle-mounted
      transceivers, comprise one of the largest sources of RFI. Some medical devices
      are especially sensitive to the type of digital modulation that some of the
      wireless communications devices utilize. The prevailing international standard
      for the RF immunity of medical devices is the 1993 revision of the International
      Electro-technical Commission (IEC) Standard IEC 60601-1-2. This standard sets a
      minimum immunity level of 3 volts per meter (V/m) in the 26-1000 MHz frequency
      range. For non-life supporting devices, testing is required only at the specific
      frequencies of 27.12, 40.68, and 915 MHz. Technology exists to protect, or
      "harden," most medical devices from RF fields that are much more intense than the
      3 V/m level specified in present RFI standards. Most of these techniques,
      including shielding, grounding, and filtering, are not costly if they are
      incorporated into the initial design of the electronics system. COMAR recommends
      that the various parties involved in the manufacture and use of RFI-prone medical
      devices take steps to avoid serious RFI problems that may lead to safety hazards.
      Medical device manufacturers should design and test their products to ensure
      conformance with current RFI standards and educate the users of their devices
      about the possible symptoms of potential RFI. If there exists the possibility of
      RFI problems to medical devices, steps should be taken to ensure that all sources
      of RF energy be kept at a sufficient distance.

PMID- 9604712
TI  - Effects of chronic treatment with indomethacin at clinically relevant doses on
      intestinal tissue 6-keto prostaglandin F1 alpha and leukotriene B4 level in
      relation to gastroenteropathy.
AB  - This study investigated the effects of indomethacin at clinically relevant doses
      and its chronic usage on intestinal pathology, survival time and intestinal
      tissue 6-keto prostaglandin F1 alpha and leukotriene B4 level in rats during
      various periods with different doses. Indomethacin was administered ranging from
      0.625 to 5 mg/kg. When used in doses of 0.625 and 1.25 mg/kg, indomethacin caused
      no apparent intestinal lesions or death during a treatment period of 30 days. On
      the other hand, all rats died in 7 days when 5 mg/kg of indomethacin was given.
      Mortality rate reached 53.3% in seven days in the group where 3.75 mg/kg
      indomethacin was given. The minimal dose of indomethacin, which induced
      intestinal ulcer and death, was 2.5 mg/kg. The main pathological findings were
      intestinal ulcers, but no macroscopic and microscopic changes were observed in
      the stomach. Intestinal tissue 6-keto prostaglandin F1 alpha and leukotriene B4
      levels were quantified by enzyme immunoassay after homogenisation and extraction
      of tissue. In dose-dependent studies, only the dose of indomethacin, 3.75 mg/kg,
      significantly inhibited intestinal tissue 6-keto prostaglandin F1 alpha levels
      during seven days application period (197.39 +/- 24.26 vs 383.66 +/- 46.68 ng/g
      tissue, treatment vs control). 2.5 mg/kg of indomethacin caused no intestinal
      ulceration on 4th day, however, it significantly inhibited intestinal tissue 6
      keto prostaglandin F1 alpha levels on 4th day in time-dependent studies (190.3 +/
      26.62 vs 383.66 +/- 46.68 ng/g tissue, treatment vs control). Neither dose
      dependent nor time-dependent indomethacin administration changed intestinal
      tissue leukotriene B4 level. The results of this study indicated that
      indomethacin produced enteropathy rather than gastropathy when used chronically
      in clinically relevant doses in rats. Inhibition of prostaglandin synthesis,
      which was estimated by quantification of intestinal tissue 6-keto prostaglandin
      F1 alpha level, seemed not to be a prerequisite for its enteropathic effect.

PMID- 9604713
TI  - Activation of transcription factors and IL-8 expression in neutrophils stimulated
      with lipopolysaccharide from Porphyromonas gingivalis.
AB  - DNA binding activity of NF-kappa B and AP-1 were examined in neutrophils
      stimulated with LPS purified from P. gingivalis, a major pathogenic bacteria of
      periodontitis lesion. Porphyromonas gingivalis LPS enhanced the activity reaching
      a peak at a concentration of 500 ng/ml in the absence of serum. The NF-kappa B
      activation stimulated with 10 ng/ml of P. gingivalis LPS was suppressed
      approximately 44% by treatment of neutrophils with anti-CD14 antibody under the
      presence of serum. Increase in the steady-state IL-8 mRNA level was concomitantly
      observed by stimulation of neutrophils with 500 ng/ml of P. gingivalis LPS under
      the absence of serum. These results indicate that P. gingivalis LPS activates NF
      kappa B and AP-1 in both serum-dependent and -independent manners, followed by
      increased IL-8 transcription in neutrophils, and suggested a role for P.
      gingivalis LPS in IL-8 synthesis by neutrophils in inflamed gingiva and GCF.

PMID- 9604714
TI  - Oxidation of the mesangial matrix metalloproteinase-2 impairs gelatinolytic
      activity.
AB  - Glomerulosclerosis is characterized by an accumulation of mesangial extracellular
      matrix. Oxygen radicals are strongly implicated in glomerular injury but it is
      unclear by what mechanism they could modulate matrix turnover dynamics. We
      evaluated whether oxidation of the 72 kD mesangial matrix metalloproteinase-2
      (MMP-2), the major mesangial matrix-degrading enzyme, could alter its
      gelatinolytic activity. Oxidation of the MMP-2 using a FeCl3/ascorbate system
      resulted in impaired ability to degrade [3H]gelatin compared to control. Samples
      were also subjected to SDS-PAGE gelatin substrate zymography. At the 72 kD
      position a significant impairment of gelatinolytic activity of oxidized samples
      was observed, a decrease attenuated by coincubation of samples with the
      FeCl3/ascorbate system plus the radical spin trap N-tert-butyl-alpha
      phenylnitrone suggesting specificity of oxidative changes in the decrease in
      enzymatic activity. These data represent the first report demonstrating that
      oxidation of the MMP-2 diminishes its activity and suggest a previously
      undescribed mechanism by which oxygen radicals may contribute to altered turnover
      of extracellular matrix.

PMID- 9604715
TI  - Enhancement of the effect of methotrexate on collagen II induced arthritis in
      mice by nicotinamide.
AB  - Treatment with a combination of 10 mg/kg i.p. methotrexate and 100 mg/kg i.p.
      nicotinamide inhibits the development of collagen II induced arthritis in male
      DBA/1 X B.10(4R) mice, as assessed by the arthritic index and whole blood
      chemiluminescence. The effect is much more pronounced than with either
      methotrexate or nicotinamide alone at the same concentrations. Determination of
      GOT and GPT levels in the blood revealed that the treatment causes no toxic side
      effects on the liver.

PMID- 9604717
TI  - Arachidonic acid (AA) and tetradecanoylphorbol acetate (TPA) exert systemic
      effects when applied topically in the mouse.
AB  - We studied the systemic actions of topically applied arachidonic acid (AA) and
      tetradecanoylphorbol acetate (TPA) in the mouse. AA or TPA-induced ear edema,
      increases in vascular permeability, eicosanoid levels, neutrophil and mononuclear
      influx were determined in both phlogogen-treated and contralateral vehicle
      treated ear of each mouse and were compared with vehicle-treated ears from
      control mice. Edema and vascular permeability increases appeared only in AA- or
      TPA-applied ears. Moreover, in contralateral ears from AA-treated mice an
      increase in 6-keto-PGF1 alpha and LTB4 was found. Only LTB4 increased in the
      contralateral ear after TPA. Contralateral ears from AA- or TPA-treated mice also
      showed a significant increase in MPO levels. The increased levels of 6-keto-PGF1
      alpha but not those of LTB4 in contralateral ears were reduced by indomethacin
      applied simultaneously with the phlogogen. AA also increased plasma and serum
      levels of LTB4, but not those of 6-keto-PGF1 alpha. In contrast, TPA increased
      plasma and serum levels of 6-keto-PGF1 alpha and LTB4. The results show that both
      AA and TPA applied topically exert systemic effects.

PMID- 9604716
TI  - Binding of latent matrix metalloproteinase 9 to fibrin: activation via a plasmin
      dependent pathway.
AB  - The binding of two matrix metalloproteinases (MMP) to fibrin was evaluated. MMP-2
      (72-kDa) and MMP-9 (92-, 130-, and 225-kDa) were selected since both contain a
      fibronectin-like region and fibronectin binds fibrin. Gelatin zymography
      indicated selective and dose dependent binding of MMP-9 to fibrin. No MMP-2
      binding to fibrin occurred. Densitometry revealed that the 130- and 225-kDa forms
      demonstrated similar sigmoidal binding profiles whereas 92-kDa uptake was
      hyperbolic. Fibronectin and TIMP-1 competition studies indicated that the
      fibronectin and C-terminal MMP-9 domains, respectively, were not involved with
      fibrin binding. The MMP-9 collagen-like region may be of regulatory significance
      since type I and II fibrillar and type IV basement membrane collagens
      demonstrated fibrin binding. During fibrinolysis, latent fibrin-bound MMP-9 was
      processed to lower molecular weight forms consistent with proteolytic activation.
      This process was inhibited by epsilon-aminocaproic acid, indicating a plasmin
      dependent pathway. The significance of these findings to procoagulant activity
      and MMP-mediated extracellular matrix destruction during inflammation and tumor
      invasion and metastasis is discussed.

PMID- 9604718
TI  - Keratinocyte growth factor decreases pulmonary edema, transforming growth factor
      beta and platelet-derived growth factor-BB expression, and alveolar type II cell
      loss in bleomycin-induced lung injury.
AB  - Keratinocyte growth factor (KGF), a potent growth factor for type II pneumocytes
      and Clara cells, has been shown to prevent the end-stage pulmonary fibrosis and
      mortality in a rat model of bleomycin-induced lung injury. In this study,
      protective effects of KGF were explored during the earlier course of bleomycin
      induced lung injury by studying protein exudation in alveolar edema fluids,
      pulmonary expression of transforming growth factor-beta (TGF beta) and platelet
      derived growth factor-BB (PDGF-BB), and changes in type II pneumocytes and Clara
      cells after i.t. (intratracheal) bleomycin injection following KGF- or saline
      pretreatment in rats. Total protein in bronchoalveolar lavage (BAL) fluids after
      bleomycin injury from KGF-pretreated rats was significantly lower than the levels
      in saline-pretreated rats. TGF beta protein in BAL fluids which peaked at day 3
      after i.t. bleomycin in saline-pretreated lungs was not significantly increased
      at any time points in KGF-pretreated rats. PDGF-BB protein in whole lung tissues
      of KGF-pretreated rats also remained near normal throughout the course after i.t.
      bleomycin, in contrast to the significant increase in saline-pretreated rats.
      Numbers of type II pneumocytes and Clara cells in KGF-pretreated lungs after a
      high dose of bleomycin were close to the normal in intact lungs. At the same dose
      of bleomycin injury, type II pneumocytes in saline-pretreated lungs were markedly
      decreased, while the number of Clara cells in these rats was relatively preserved
      as the pre-injury level. In conclusion, KGF prevents bleomycin-induced end-stage
      pulmonary injury and mortality probably at least partly by decreasing protein
      rich pulmonary edema, protein expression of fibrogenic cytokines TGF beta and
      PDGF-BB, and type II cell loss during the course of lung injury.

PMID- 9604720
TI  - Role of the medical director of the operating room.

PMID- 9604719
TI  - In vivo recruitment of neutrophils: consistent requirements for L-arginine and
      variable requirements for complement and adhesion molecules.
AB  - The current studies examined the mechanisms of neutrophil recruitment into the
      rat peritoneal cavity following injection of glycogen and into rat lungs
      following alveolar deposition of IgA immune complexes or airway instillation of
      phorbol ester (PMA). Unexpectedly, in each model a requirement for L-arginine for
      neutrophil recruitment was demonstrated, since administration of the L-arginine
      analogue, NG-monomethyl L-arginine acetate (L-NMA), greatly reduced neutrophil
      accumulation as assessed by quantitation of neutrophils in peritoneal exudates
      and bronchoalveolar lavage fluids, and by lung myeloperoxidase content. In the
      case of IgA immune complex deposition, lung recruitment of neutrophils was also
      suppressed by soluble recombinant human complement receptor-1 (sCR1) and antibody
      to CD18 but not by antibody to E-selection. In contrast, neutrophil accumulation
      following airway instillation of PMA exhibited, surprisingly, no requirement for
      complement but requirements for both E-selection and CD18. These data demonstrate
      variable requirements for complement, E-selectin and CD18 but a consistent
      requirement for L-arginine for neutrophil recruitment. These findings provide
      evidence suggesting that L-arginine or its derivatives regulate neutrophil
      recruitment.

PMID- 9604721
TI  - Association of operating room nurses.

PMID- 9604722
TI  - Defining measurable OR-PR scheduling, efficiency, and utilization data elements:
      the Association of Anesthesia Clinical Directors procedural times glossary.

PMID- 9604723
TI  - Management concepts in the operating room suite.

PMID- 9604724
TI  - Financial and materiel management.
AB  - Hospitals have to purchase new technology, update equipment, and replenish
      supplies continually to meet the needs of patients and the medical and nursing
      staff in a sound financial way. Thus, inventories must be maintained accurately
      and adequately with proper controls. Awareness of the cost of capital and
      operational supplies is essential to meeting budget allocations. With or without
      centralized buying, the MM department has the expertise to assist every
      department in purchasing to meet its needs and in setting and resetting inventory
      levels for its supplies. Explanations and formulas for handling capital equipment
      and regular supplies and some formats have been presented to facilitate the
      process. Because OR items are both expensive and numerous and OR storage space
      the most costly space in the hospital, physicians and nurse managers must
      understand the financial processes and inventory management and educate their
      staffs in these matters.

PMID- 9604725
TI  - Strategies to control anesthetic practice costs.

PMID- 9604726
TI  - Miscellaneous operational issues in the operating room.
AB  - As physicians in the OR suite, anesthesiologists' interests extend beyond the
      technical issues of rendering anesthesia care, and a number of topics germane to
      problems in the OR and anesthesia department have been covered. More and more
      anesthesiology practices are locating outside the "safety" zone of the hospital;
      thus, it becomes encumbent on the physicians working in those environments to be
      aware of the regulations, safety standards, and hazards in order to provide a
      safe environment for their patients and to run a well-managed OR suite.

PMID- 9604727
TI  - Outcomes measurement in the operating room suite.
AB  - The objectives of quality improvement in the OR include improved perioperative
      care of the patient and OR efficiency, decreased hospital length of stay, and
      decreased costs. We submit that multidisciplinary outcome measurement is a
      prerequisite for coordinated outcomes management to achieve quality patient care
      in an effective, efficient, and financially responsible way, and we provide a
      guide to do so. The data obtained by such cross-discipline study can identify the
      need for patient, family, and/or staff education, improved interaction and
      collaboration across disciplines, revision of clinical paths, and improved
      hospital systems as well as benchmarking the performance of the OR against local
      or national standards.

PMID- 9604728
TI  - Comprehensive strategies for developing a performance appraisal system for the
      operating room.

PMID- 9604729
TI  - Comparative study on the clinical efficacy of theophylline variable serum
      concentrations therapy and round-the-clock therapy.
AB  - Depending on the administration method, highly effective therapeutic variable
      serum concentrations (VSC) of theophylline can be attained only in the time range
      of frequent asthma attacks. We used an oral sustained-release theophylline
      preparation in seven patients with bronchial asthma (two males and five females;
      mean age: 38.7 years) who had required more than two admissions per year due to
      bronchial asthma attacks, despite being treated with round-the-clock (RTC)
      therapy of theophylline and inhalation of steroids. We examined the annual
      frequency of admissions and the peak expiratory flow rate (PEFR) in remission.
      Even though no difference was noted in the serum concentrations of theophylline
      in the morning (the time range of attack) between RTC therapy and VSC therapy,
      the mean number of admissions during VSC therapy was 1.14, compared with 3.86
      recorded during RTC therapy (p < 0.001). PEFR in remission showed a significant
      improvement with VSC therapy, compared with PEFR recorded during RTC therapy (p <
      0.05). VSC therapy proved to be useful for patients who failed to attain
      favorable control of asthma attacks by RTC therapy.

PMID- 9604730
TI  - Tramadol in the fibromyalgia syndrome: a controlled clinical trial versus
      placebo.
AB  - This study assessed the analgesic action of tramadol compared with placebo in
      patients suffering from fibromyalgia syndrome. Twelve patients (11 females, one
      male) were treated according to a double-blind crossover experimental design.
      Each patient, after signing informed consent, was randomly allocated to either
      tramadol (100 mg ampul in 100 ml given intravenously in 15 min doses) or placebo
      for a single dose treatment. At the second visit, patients crossed over to the
      other drug for a further single dose treatment. There was a wash-out period of 1
      week. Nine patients completed the study, while in three cases (two tramadol, one
      placebo) the study was discontinued due to the onset of side effects. The
      assessment of efficacy, carried out at the baseline and 15 min and 2 hours after
      administration of each dose, involved the use of a visual analog scale (VAS 100
      mm) for spontaneous pain and pressure dolorimetry (kg/cm2) at 12 "symptomatic"
      tender points and nine "control" tender points for fibromyalgic pain. During the
      first treatment cycle effective control of spontaneous pain was achieved with
      tramadol, which determined a reduction of 20.6% while with the placebo
      spontaneous pain increased by 19.8%. With pressure dolorimetry there were no
      clinically important differences observed after either active treatment or
      placebo. The contrasting results found in the present study could be a stimulus
      for the organization of new projects, which may lead to the identification of an
      optimal therapeutic approach for fibromyalgic patients, also using tramadol for
      long periods.

PMID- 9604731
TI  - The postoperative analgesic efficacy and safety of piroxicam (FDDF) and naproxen
      sodium.
AB  - The aim of the present study was to compare the analgesic efficacy of piroxicam
      FDDF (fast dissolving dosage form) with naproxen sodium, following bilateral
      removal of impacted third molars. A double-blind, randomized, crossover,
      analgesic trial was carried out on 40 patients undergoing surgical removal of one
      lower third molar at each visit. The analgesic efficacy of a single dose regimen
      of piroxicam-FDDF (40 mg, Feldene Flash, Pfizer, Turkey) was compared with
      naproxen sodium (550 mg, Anaprotab, Sanli, Turkey). Pain intensity was measured
      on a category-rating scale during the 8-h period after drug administration. Each
      patient evaluated the efficacy of the study medication at 15, 30, 45, 60, 90 and
      120 min, and then hourly for up to 8 h of drug ingestion. Additional key efficacy
      measures were also determined (pain intensity difference [PID], sums of pain
      intensity difference [SPID], total pain relief [TOTPAR], peak pain relief, number
      of observations at which pain was half-relieved, overall evaluation of study
      medication effectiveness, and time to medication with a back-up analgesic). The
      data were analyzed by paired Student's t-test and one-way analysis of variance
      (ANOVA). Results are expressed as means +/- SEM, and p < 0.05 was taken as
      statistically significant. The PID and pain relief scores of the piroxicam-FDDF
      group were significantly greater than those for the naproxen sodium group at 15,
      30, 45 and 60 min (p < 0.01). After 90 min to 8 h, no statistical significance
      was revealed among the two test groups (p > 0.05). The peak pain relief, maximal
      analgesic effect, SPID, TOTPAR values, adjusted mean number of observations with
      pain at least half-relieved, and the final overall evaluation records were all
      superior for piroxicam-FDDF (p < 0.05). The results of this study clearly show
      that the analgesic efficacy of piroxicam-FDDF is superior to naproxen sodium in
      the treatment of pain following oral surgery for the removal of impacted third
      molars.

PMID- 9604732
TI  - Liver toxicity profile in gold-treated Egyptian rheumatoid arthritis patients.
AB  - The objective was to evaluate the rationale for liver needle biopsy versus blood
      liver functional tests in monitoring the incidence of hepatotoxicity in Egyptian
      rheumatoid arthritic patients treated with gold compounds. Forty patients (12
      males, 28 females) were randomly selected out of 258 Egyptian rheumatoid
      arthritic patients treated with sodium auro-thiomalate during the past 4 years.
      The minimum duration of treatment was 40 weeks. The methods used were firstly,
      liver function tests (serum glutamic-oxaloacetic transaminase, serum glutamic
      pyruvic transaminase, total serum bilirubin and total serum albumin) before,
      weekly during and after administration of sodium auro-thiomalate. Secondly, a
      needle liver biopsy was conducted by using the tru-cut needle. Then liver
      histology was graded according to Roenigk for grading liver toxicity. Viral
      hepatitis markers (hepatitis B surface antigen, anti-hepatitis C virus were done
      for monitoring viral hepatitis. Finally, the liver tissue contents of heavy
      metals were counted in the cases that showed grade IIIB histological changes. The
      results showed that none of the studied cases developed any clinically
      significant liver disease during the course of chrysotherapy. Blood liver
      function tests were of normal value throughout the course of drug administration.
      According to Roenigk grading, 20 patients (50%) showed grade I liver changes, and
      the other 20 patients showed liver changes of grades II and III (four grade II,
      eight grade IIIA, and another eight grade IIIB). None of the patients showed
      grade IV liver changes. It was concluded that blood liver tests are not the most
      sensitive methods to detect hepatotoxicity in gold-receiving Egyptian rheumatoid
      arthritic patients. Needle liver biopsy is not superior in detecting liver
      toxicity, compared with routine laboratory liver function tests, because of its
      complications. Rheumatoid arthritic patients with a potential risk of clinically
      significant liver disease should not be exposed to the risk of gold salt therapy.
      Pretreatment HLA-DR genetic typing may be a good detector for rheumatoid
      arthritic patients with potential risk of hepatotoxicity.

PMID- 9604733
TI  - Galactosaminoglucuronoglycan sulphate in the treatment of osteoarthritis:
      clinical efficacy and tolerance of oral and intra-articular administrations.
AB  - The clinical efficacy and the tolerance of galactosaminoglucuronoglycan sulphate
      (GGGS), administered both orally and intra-articularly were evaluated for the
      treatment of generalized and localized osteoarthritis (OA). The study included
      154 patients: 52 treated orally with GGGS, observed during three periods of three
      consecutive months of therapy followed by eight weeks of withdrawal, 52 treated
      only with non-steroidal anti-inflammatory drugs (NSAIDs), and 50 patients treated
      two times in a year with a total of twelve (6 x 2) knee intra-articular weekly
      injections. The tolerance to GGGS was excellent, and the monitoring of the
      clinical measurements revealed a significant improvement of the articular data
      with a decreasing of NSAID's consumption.

PMID- 9604734
TI  - Current concepts of diabetes mellitus.

PMID- 9604735
TI  - The epidemiology of diabetes mellitus and diabetic retinopathy.
AB  - An apparent epidemic of diabetes is occurring in adults worldwide. This trend
      seems to be associated with socioeconomic and lifestyle changes. The population
      of developing countries and some communities within developing countries are at
      higher risk. Diabetic eye disease and its complications, especially diabetic
      retinopathy, are a leading cause of blindness and visual dysfunction in adults in
      economically developed societies. Epidemiological studies of the impact of
      diabetic eye disease in developing countries are scarce. Risk factors for the
      development and progression of diabetic retinopathy include, among others,
      hyperglycemia, genetic factors, race, duration of the disease, arterial
      hypertension, and proteinuria.

PMID- 9604736
TI  - The cornea in diabetes mellitus.
AB  - Diabetes mellitus has a significant effect on morphological, metabolic,
      physiological, and clinical aspects of the cornea. Morphological changes are
      manifest in the corneal epithelium, epithelial basement membrane and basement
      membrane complexes, stroma, and endothelium. The homeostasis of these structures
      can be altered by diabetes in both the non-stressed and the stressed cornea,
      causing myriad primary and postoperative manifestations. The polyol pathway
      appears to be involved in some of the pathophysiology mechanisms leading to these
      clinical entities and appears also to play a role in the treatment of some
      diabetic pathological processes associated with diabetes mellitus.

PMID- 9604737
TI  - The lens and cataract in diabetes.

PMID- 9604738
TI  - Diabetes mellitus and glaucoma.

PMID- 9604739
TI  - Angiogenic factors in diabetic ocular disease: mechanisms of today, therapies for
      tomorrow.

PMID- 9604740
TI  - Retinal blood flow in diabetes.

PMID- 9604741
TI  - Screening for diabetic retinopathy.

PMID- 9604742
TI  - Diabetic retinopathy treatment trials: a review.

PMID- 9604743
TI  - Vitrectomy for complications of diabetic retinopathy.

PMID- 9604744
TI  - Orbital pathology associated with diabetes mellitus.
AB  - Diabetes mellitus may be associated with or result in diverse orbital and adnexal
      problems. It may include mild manifestations, such as blepharoptosis,
      blepharitis, xanthomas, increased tear-film glucose levels, and calcification of
      the trochlear apparatus. More severe findings involve third, fourth, and sixth
      cranial neuropathies. Finally, the physician always should be alert for the
      possibility of orbital infections in the diabetic population, especially the life
      threatening rhinocerebral mucormycosis.

PMID- 9604745
TI  - Ocular findings in children with diabetes.

PMID- 9604746
TI  - Influence of pregnancy on the evolution of diabetic retinopathy.

PMID- 9604748
TI  - Neuroophthalmological manifestations of diabetes mellitus.

PMID- 9604747
TI  - Anesthesia for the diabetic patient undergoing ophthalmological procedures.

PMID- 9604749
TI  - Diabetes 2000.

PMID- 9604750
TI  - Preimplantation genetics.

PMID- 9604751
TI  - Preimplantation diagnosis of thalassemias.
AB  - PURPOSE: Preimplantation genetic diagnosis (PGD) is an important option for
      couples at risk of having children with beta-globin mutations to avoid selective
      abortions of affected fetuses following prenatal diagnosis. METHODS: We performed
      PGD for thalassemia in 12 clinical cycles (IVS1-110, and IVS-745 mutations) using
      biopsy of the first and second polar bodies (PBs) extruded from oocytes during
      maturation and fertilization, coupled with nested polymerase chain reaction
      analysis and restriction digestion. RESULTS: A total of 118 oocytes was obtained,
      of which 78 had results for both the first and the second PBs. This resulted in
      the selection and transfer of 30 unaffected embryos (2.5 embryos per cycle). To
      avoid a possible misdiagnosis due to allele dropout (ADO), we have also
      introduced simultaneous detection of two highly polymorphic linked markers, a
      short tandem repeat immediately at the 5' end of the globin gene and HUMTH01
      which is a syntenic short tandem repeat. The application of multiplex polymerase
      chain reaction of the beta-globin gene and linked polymorphic markers enabled
      detection of ADO in five first PBs, thus avoiding the transfer of potentially
      affected embryos resulting from their corresponding oocytes. CONCLUSIONS:
      Confirmation studies of the embryos resulting from the oocytes predicted to
      contain an affected gene confirmed the diagnosis in 98% of the cases, thus
      demonstrating the accuracy and reliability of PB PGD of thalassemia mutations.
      The application of PB analysis in six patients resulted in two ongoing
      pregnancies with a thalassemia-free fetus already confirmed in both of them by
      prenatal diagnosis.

PMID- 9604752
TI  - Epigenetic influences on oocyte developmental competence: perifollicular
      vascularity and intrafollicular oxygen.
AB  - PURPOSE: Studies indicating that the developmental competence of the human oocyte
      is influenced by the level of intrafollicular oxygen are described. METHODS:
      Perifollicular vascularity and dissolved oxygen content were determined by color
      Doppler ultrasonography and analysis of follicular fluid at ovum retrieval,
      respectively, in stimulated cycles for in vitro fertilization. RESULTS:
      Differences in the degree of perifollicular vascularity correlate with
      differences in the dissolved oxygen content of the corresponding follicular
      fluid. Oocytes with cytoplasmic and chromosomal disorders and embryos with
      multinucleated blastomeres and limited developmental ability were derived
      predominantly from underoxygenated follicles. Findings from several studies
      indicate that embryos with the highest implantation potential originate from
      follicles that are well-vascularized and oxygenated. CONCLUSIONS: Follicular
      vascularity and oxygen content appear to be important determinants of oocyte
      competence. Possible causes of differences in follicle-specific vascularity and
      the potential effects of severe hypoxia on the normality of molecular and
      cellular processes during follicle growth and preovulatory development are
      discussed.

PMID- 9604753
TI  - Recent progress in mammalian cloning.
AB  - PURPOSE: Our purpose was to review recent progress in the use of nuclear transfer
      technology to produce genetically identical mammals. METHODS: A literature review
      was conducted. RESULTS: The reasons for cloning nonhuman mammals are manyfold
      including commercial, biomedical, and basic research applications. Individual
      steps in the nuclear transfer process are itemized, along with a detailed
      description of the specific approaches used in the production of Dolly, NETI, and
      DITTO. The potential application of nuclear transfer in the treatment of human
      infertility is also considered, along with bioethical concerns. Finally, insights
      are provided concerning the future application of cloning technology in rhesus
      macaques. CONCLUSIONS: The cloning of a lamb (Dolly) from an adult, mammary gland
      cell coupled with the successful production of rhesus monkeys (NETI and DITTO) by
      nuclear transfer of embryonic cells marks the beginning of a "Golden Age" in the
      development and application of somatic cell cloning technology in mammals.

PMID- 9604754
TI  - Genetics of human sperm.
AB  - PURPOSE: Chromosome abnormalities in sperm were studied by fluorescence in situ
      hybridization to determine the frequency and distribution of abnormalities in
      normal men and the effect of donor age on the frequency of abnormalities. Studies
      of chemotherapy and infertility patients assessed any increased risk in these
      populations. METHODS: Multicolor fluorescence in situ hybridization was performed
      on the sperm samples to assess aneuploidy frequencies for chromosomes 1, 2, 4, 9,
      12, 13, 15, 16, 18, 20, 21, X, and Y as well as "sex ratios" and frequencies of
      diploid sperm. RESULTS: Most chromosomes yielded disomy estimates of
      approximately 0.1%, whereas the frequencies for chromosome 21 and the sex
      chromosomes were significantly elevated. The only chromosome to show a
      significant paternal age effect was YY disomy. Chemotherapy patients did not have
      an increased risk of aneuploid sperm 2-13 years after treatment. Infertility
      patients had an increased risk of disomy for chromosome 1, 13, 21, and XY.
      CONCLUSIONS: Multicolor fluorescence in situ hybridization analysis allows
      comparison of sperm from various populations of men and has demonstrated that
      infertile patients have a significant increase in the frequency of aneuploid
      sperm.

PMID- 9604755
TI  - The control of mammalian female meiosis: factors that influence chromosome
      segregation.

PMID- 9604756
TI  - Allele dropout in polar bodies and blastomeres.
AB  - PURPOSE: Because allele dropout (ADO) is frequently observed in single-cell
      polymerase chain reaction analysis, it is important to develop a method for
      efficient detection of ADO, in order to avoid possible misdiagnosis in
      preimplantation diagnosis. METHODS: We introduced a simultaneous amplification of
      mutant genes and linked polymorphic markers, such as a 4-bp repeat (GATT) at the
      3' end of intron 6 in the cystic fibrosis (CF) gene and a short tandem repeat at
      the 5' end of the beta-globin gene. Three types of single heterozygous cells were
      studied for the amplification of both alleles, including 150 blastomeres, 1615
      fibroblasts, and 170 first polar bodies, obtained from patients at risk for
      having children with cystic fibrosis (delta F-508 mutation) or sickle cell
      disease. RESULTS: ADO rates of as high as 33.3% for delta F-508 mutation and
      22.8% for beta-globin gene were observed in single blastomeres, compared to 7.1
      and 7.7% in single fibroblasts and 5.9 and 9.6% in first polar bodies,
      respectively. The application of simultaneous amplification of the above linked
      polymorphic markers allowed detection of more than half of the cases of ADO in
      blastomeres (19.4% for cystic fibrosis and 12.3% for beta-globin gene) and almost
      all ADOs in polar bodies, particularly when the two-step sequential analysis of
      the first and second polar body was applied in preimplantation diagnosis of
      single gene disorders. CONCLUSIONS: Simultaneous amplification of linked
      polymorphic markers in single-cell DNA analysis of single-gene defects is an
      efficient method for avoiding the risk of misdiagnosis in preimplantation
      diagnosis.

PMID- 9604757
TI  - Comparison of FISH PRINS, and conventional and fluorescent PCR for single-cell
      sexing: suitability for preimplantation genetic diagnosis.
AB  - PURPOSE: Although conventional polymerase chain reaction (PCR) was the first
      method used for sexing in preimplantation genetic diagnosis, fluorescent in situ
      hybridization (FISH) has become the method of choice. Recently two new
      techniques, primed in situ synthesis (PRINS) and fluorescent PCR, have been
      developed. This study compares the reliability and accuracy of these four
      techniques in single cells. RESULTS: In buccal cells, fluorescent PCR and FISH
      had similar reliability (94 and 93%) and accuracy (97 and 96%) rates. The
      reliability and accuracy of PRINS (91 and 25%) and conventional PCR (79 and 89%)
      were lower. In human blastomeres, FISH and fluorescent PCR had similar
      reliability (100%, 717; 95%, 190/201) rates. Accuracy rates were 71% (517) and
      99% (188/190) for FISH and fluorescent PCR, respectively, however, too few
      blastomeres were analyzed by FISH for meaningful comparison. However, when these
      data are compared with published data, the method of choice for blastomere sexing
      appears to be fluorescent PCR. CONCLUSIONS: Flouroscent PCR has major
      implications for PGD.

PMID- 9604758
TI  - Rapid trisomy diagnosis (21, 18, and 13) using fluorescent PCR and short tandem
      repeats: applications for prenatal diagnosis and preimplantation genetic
      diagnosis.
AB  - PURPOSE AND METHODS: Prenatal diagnosis of fetal trisomies is usually performed
      by cytogenetic analysis from amniotic fluid. This requires lengthy laboratory
      procedures and high costs and is unsuitable for large-scale screening of pregnant
      women. An alternative method, which is rapid and inexpensive and may potentially
      be suitable for diagnosing trisomies even from single fetal cells, is the
      fluorescent polymerase chain reaction (F-PCR) using polymorphic small tandem
      repeats (STRs). RESULTS: In this paper we present data demonstrating that
      fluorescent PCR amplification of STRs can be used for rapid diagnosis of trisomy
      21, trisomy 18, and trisomy 13 and can be successfully applied to both prenatal
      diagnosis and diagnosis of single cells. This study also reports significant
      numbers of prenatal diagnoses using quantitative fluorescent PCR. CONCLUSIONS: We
      believe that further studies of greater numbers of samples will determine the
      absolute reliability of this technique. These results also provide a model for
      trisomy diagnosis from single cells using multiple STR markers for either
      preimplantation genetic diagnosis or, potentially, diagnosis from fetal cells
      isolated from maternal blood.

PMID- 9604759
TI  - Chromosomal mosaicism in cleavage-stage human embryos and the accuracy of single
      cell genetic analysis.
AB  - PURPOSE: Our purpose was to assess the effect of chromosomal mosaicism in
      cleavage-stage human embryos on the accuracy of single-cell analysis for
      preimplantation genetic diagnosis. METHODS: Multicolor fluorescence in situ
      hybridization with X, Y, and 7 or X, Y, 7, and 18 chromosome-specific probes was
      used to detect aneuploidy in cleavage-stage human embryos. RESULTS: Most nuclei
      were diploid for the chromosomes tested but there was extensive mosaicism
      including monosomic, double-monosomic, nullisomic, chaotic, and haploid nuclei.
      CONCLUSIONS: Identification of sex by analysis of a single cleavage-stage nucleus
      is accurate but 7% of females are not identified. One or both parental
      chromosomes 7 were absent in at least 6.5% of the nuclei. With autosomal
      recessive conditions such as cystic fibrosis, carriers would be misdiagnosed as
      normal or affected. With autosomal dominant conditions, failure to analyze the
      affected parents allele (1.6-2.5%) would cause a serious misdiagnosis and
      analysis of at least two nuclei is necessary to reduce errors.

PMID- 9604760
TI  - Preimplantation genetic diagnosis of human embryos for Marfan's syndrome.
AB  - PURPOSE: Single-cell nested polymerase chain reaction (PCR) and Ddel endonuclease
      digestion were used to detect the presence of a Marfan's syndrome mutation in
      human preimplantation embryos derived from in vitro fertilization (IVF). These
      procedures were conducted to eliminate the possibility of transmission of the
      affected allele from the father to his offspring. The mutation on chromosome 15
      is transmitted as an autosomal dominant trait, and the chance of having a child
      affected with the disease is 50%. METHODS: A couple presented to the Program for
      In Vitro Fertilization, Reproductive Surgery and Infertility for preimplantation
      genetic diagnosis. IVF was performed and embryo biopsy was done on day 3 embryos.
      Single blastomeres were removed from embryos and subjected to nested PCR analysis
      and endonuclease digestion to detect a Marfan's syndrome mutation located on
      chromosome 15 inherited from the father. RESULTS: Thirteen oocytes were injected
      with spermatozoa using intracytoplasmic sperm injection, and nine fertilized
      normally. Following embryo biopsy and polymerase chain reaction amplification
      Ddel endonuclease digestion, five embryos were detected that were positive for
      the mutation. The four non-affected embryos were transferred to the uterus,
      resulting in a healthy and normal ongoing pregnancy.

PMID- 9604761
TI  - Preimplantation diagnosis of common aneuploidies by the first- and second-polar
      body FISH analysis.
AB  - PURPOSE: A low pregnancy rate in in vitro fertilization (IVF) patients of
      advanced maternal age may be caused by aneuploidies originating from non
      disjunction in the first or second meiotic divisions. We introduced genetic
      testing of oocytes by sampling and fluorescent in situ hybridization (FISH)
      analysis of the first and second polar bodies, to avoid fertilization and
      transfer of aneuploid oocytes in IVF patients of advanced maternal age. METHODS:
      Three hundred and sixty-three IVF patients 34 years and older participated in the
      study. Using micromanipulation procedures, the first and second polar bodies were
      removed following their extrusion from the oocytes and studied by FISH, using
      probes specific for chromosomes 13, 18, and 21 to detect oocytes with common
      aneuploidies. RESULTS: Of a total of 538 IVF cycles, 3250 oocytes were available
      for FISH analysis, with conclusive FISH results in 2742 oocytes (84.3%). As many
      as 1102 (40%) of oocytes were predicted to be aneuploid and not transferred. Of
      1640 embryos predicted to be normal, 1145 were transferred in 467 treatment
      cycles, resulting in 107 pregnancies (23%), from which 67 healthy children have
      been born, 32 pregnancies spontaneously aborted, and 15 pregnancies are ongoing
      after being confirmed normal by prenatal diagnosis. CONCLUSIONS: Preimplantation
      diagnosis by first- and second-polar body FISH analysis allows us to avoid the
      age-related risk of common aneuploidies in IVF patients of advanced maternal age.

PMID- 9604763
TI  - Incidence of chromosomal abnormalities from a morphologically normal cohort of
      embryos in poor-prognosis patients.
AB  - PURPOSE: Preimplantation genetic diagnosis of aneuploidy was performed on the
      embryos yielded by 70 poor-prognosis patients, with the aim of transferring those
      with a normal chromosomal complement, thus possibly increasing the chances of
      pregnancy. METHODS: Multicolor fluorescence in situ hybridization (FISH) was
      applied for the simultaneous detection of chromosomes X, Y, 13, 16, 18, and 21.
      Inclusion criteria were (1) a maternal age of 36 years or older (n = 33), (2)
      three or more previous in vitro fertilization cycles (n = 20), and (3) an altered
      karyotype (n = 17). RESULTS: A total of 412 embryos underwent FISH, resulting in
      234 (57%) that were chromosomally abnormal. Euploid embryos were available for
      transfer in 59 patients, generating 19 pregnancies (32%), with an implantation
      rate of 19.9%. CONCLUSIONS: High rates of chromosomally abnormal embryos in poor
      prognosis patients can determine repeated in vitro fertilization failures when
      embryo selection is performed on the basis of morphological criteria alone.
      Hence, the FISH analysis could represent the prevailing approach for the
      identification of embryos possessing full potential for developing to term.

PMID- 9604762
TI  - Spontaneous abortions are reduced after preconception diagnosis of
      translocations.
AB  - PURPOSE: Preimplantation genetic diagnosis of translocations has seldom been
      attempted. Recently, a genetic test based on analyzing polar bodies at the
      methaphase stage, following fluorescent in situ hybridization with commercially
      available whole-chromosome painting DNA probes has been presented. Here we report
      the use of this method in seven couples in whom the female was a carrier of one
      of these balanced translocations: 45,XX,der (13q;14q)(q10;q10) (two cases),
      46,XX,t(4;14)(p15.3;q24), 45,XX,der(14q;21q) (q10;q10), 46,XX,t(7;20)(q22;q11.2),
      46,XX,t(9,11)(p24;q12), 46,XX,t(14;18)(q22;q11), and 46,XX,t(3;8)(q11;q11).
      METHODS: The original method was improved in two ways. First, centromeric probes
      for one or both chromosomes involved in the translocation were added to avoid
      misdiagnosis caused by possible confusion of first polar body monovalent
      chromosomes (with two chromatids each) with single chromatids. Second, for cases
      with terminal translocations where commercially available probes do not cover
      telomere sequences, a telomere probe labeling the translocated fragment was
      added. RESULTS: A total of 26 abnormal, 18 balanced, and 22 normal eggs was
      detected. Nine normal and seven balanced embryos were transferred, resulting in
      eight (50%) implanting, of which one spontaneously aborted. To date, the
      remainder have produced karyotypically normal or balanced babies and ongoing
      pregnancies. The rate of spontaneous abortions after preimplantation genetic
      diagnosis (12.5%) was significantly reduced (P < 0.001) compared to natural
      cycles in the same patients (95%). CONCLUSIONS: With the above improvements, the
      test can characterize any translocation of maternal origin and produce a high
      pregnancy rate and an apparently low frequency of spontaneous abortion.

PMID- 9604765
TI  - Preimplantation diagnosis by FISH: the Rambam experience.
AB  - PURPOSE: Our purpose was to summarize our experience gained using fluorescence in
      situ hybridization for preimplantation diagnosis at the Rambam Medical Center.
      METHODS: Seventy-three embryos (29 cycles) were analyzed for preimplantation
      diagnosis for the following indications: advanced maternal age (> 39 years), X
      linked diseases, poor-quality embryos, repeated failure in vitro fertilization
      cycles and fast-dividing embryos. An additional 38 embryos with unequal pronuclei
      size were examined for ploidy. Biopsy of embryonic blastomeres was performed at
      the six- to eight-cell stage. Five fluorescence probes, for chromosomes X, Y, 13,
      18, and 21, were applied for ploidy detection. RESULTS: Eighty-four (87%)
      blastomeres of the 73 embryos analyzed showed clear signals. Six of the
      blastomeres were lost during spreading. Two of the embryos were destroyed
      following biopsy. No nucleus was found in five of the blastomeres, while in nine,
      more than one nucleus was verified. Transfer was performed in 10 patients (32
      embryos). Two pregnancies were achieved. Two healthy babies were born. Fifty
      seven percent of the fast-dividing embryos demonstrated normal signals. In two
      groups of embryos of unequal pronuclei size following conventional insemination
      and intracytoplasmic sperm injection, 50 and 11.4% demonstrated normal signals.
      CONCLUSIONS: The efficiency of fluorescence in situ hybridization for aneuploidy
      detection is 87 and 97% for autosomes and gonosomes, respectively. The
      preimplantation genetic diagnosis is suitable for selected in vitro fertilization
      cases including fast-dividing embryos and embryos with unequal pronuclei size
      following regular in vitro fertilization.

PMID- 9604764
TI  - Successful use of a laser for human embryo biopsy in preimplantation genetic
      diagnosis: report of two cases.
AB  - PURPOSE: The use of Tyrode's acid to drill the zona pellucida for embryo biopsy
      is the most widely used methodology in preimplantation genetic diagnosis. Instead
      of this, we propose the use of a 1.48-micron diode noncontact laser, which is
      quicker, simpler, and safer. METHODS: The laser beam was tangentially guided to
      the zona pellucida of the embryo. Depending on zona pellucida measurement, two to
      four consecutive shots of 8-22 msec were necessary to drill the zona pellucida of
      the 13 embryos biopsied for two patients (hemophilia carriers). RESULTS: Female
      embryos were replaced into the uterus of the patients (1.5 embryos/replacement).
      One single pregnancy was established (33.3% implantation rate). Coculture of
      untransferable embryos showed a blastocyst rate of 66.7% (4/6) for male embryos
      and 25% (1/4) for abnormal ones. CONCLUSIONS: These results demonstrate the
      safety and usefulness of laser methodology in preimplantation genetic diagnosis.

PMID- 9604766
TI  - FISH preimplantation diagnosis of chromosome aneuploidy in recurrent pregnancy
      wastage.
AB  - PURPOSE: Our purpose was to detect aneuploidy for chromosomes 13, 16, 18, 21, 22,
      X, and Y in preimplantation embryos from patients with a history of unexplained
      recurrent miscarriage. METHODS: Three patients with a history of unexplained
      recurrent spontaneous abortion were included in this study. Embryos were biopsied
      at the eight-cell stage, individually fixed on slides, and processed for
      fluorescent in situ hybridization (FISH). A multiple FISH protocol for seven
      chromosomes pairs (13, 16, 18, 21, 22, X, and Y) has been developed. RESULTS: A
      total of 39 embryos was studied with the multiple FISH protocol developed.
      Successful analysis of the biopsied embryos was achieved within the time limits
      usually allowed in a preimplantation diagnosis program. Analysis of the
      blastomeres showed that 17 embryos were chromosomally normal for the probes used,
      16 embryos were aneuploid, and in 6 embryos no informative results were obtained.
      CONCLUSIONS: In the patients studied, a large proportion of embryos (41%)
      exhibited chromosomal abnormalities for the probes used. Preimplantation
      diagnosis to screen for chromosome abnormalities could be a feasible approach to
      improve the possibility of successful pregnancy in these couples.

PMID- 9604767
TI  - Simultaneous detection of chromosomes X, Y, 13, 18, and 21 by fluorescence in
      situ hybridization in blastomeres obtained from preimplantation embryos.
AB  - PURPOSE: Simultaneous fluorescence in situ hybridization (FISH) was used in a
      preimplantation genetic diagnosis program to determine which embryos were normal
      for chromosomes X, Y, 13, 18, and 21. METHODS: Single blastomeres were disrupted
      and attached to glass slides using acetic acid and ethanol. Using a ratio mixture
      of chromosome enumeration DNA probes in combination with locus-specific
      identifier DNA probes, FISH was performed for the identification of chromosomes
      X, Y, 13, 18, and 21. RESULTS: Fourteen couples enrolled in IVF produced 134
      embryos for biopsy. Blastomeres subjected to five-color FISH revealed that 22% of
      embryos were normal for chromosomes X, Y, 13, 18, and 21. In addition, 52% were
      abnormal and no results could be detected for 25%. Twelve couples underwent
      embryo transfer, two couples did not receive embryos due to lack of any normal
      embryos, and three couples became pregnant. CONCLUSIONS: The simultaneous
      detection of five-color FISH is a feasible method to detect aneuploidy in
      preimplantation embryos from women of advanced maternal age.

PMID- 9604768
TI  - Do alterations in the sex ratio occur at fertilization? A case report using
      fluorescent in situ hybridization.
AB  - PURPOSE: The mechanisms by which the sex ratio might be altered at fertilization
      were reviewed, following a case of preimplantation gender analysis revealing a
      significantly skewed proportion of male-to-female embryos. METHODS: The case of a
      known carrier of X-linked hydrocephalus with a history of three affected male
      pregnancies is presented. Her husband's family history consisted of a strong
      increase in the number of males relative to females. She had four cycles of
      stimulated in vitro fertilization, with sex chromosome analysis using fluorescent
      in situ hybridization (FISH) on suitable cleavage-stage embryos. The difference
      in the sex ratio of normal male-to-female embryos was compared using a
      significance probabilities test for sex ratio. The sex ratio of sperm from a
      semen sample from the male partner was determined by FISH. RESULTS: Fifty embryos
      were suitable for analysis. A significantly higher number of normal male (n = 20)
      than normal female (n = 8) embryos was obtained (P < 0.05). The FISH assessment
      of the husband's semen analysis revealed no alteration in the normal X:Y ratio.
      CONCLUSIONS: As the sperm analysis revealed a normal X:Y ratio, an alteration in
      the embryo sex ratio might be explained by the preferential binding of Y-bearing
      sperm to the oocyte, an oocyte-related "discouragement" of binding of X-bearing
      sperm, or a postfertilization event.

PMID- 9604769
TI  - Spectral imaging in preconception/preimplantation genetic diagnosis of
      aneuploidy: multicolor, multichromosome screening of single cells.
AB  - PURPOSE: Our purpose was to evaluate the utility of spectral imaging for
      multicolor, multichromosome enumeration in human interphase cell nuclei. METHODS:
      Chromosome-specific probes labeled with different fluorochromes or nonfluorescent
      haptens were obtained commercially or prepared in-house. Metaphase spreads,
      interphase lymphocytes, or blastomeres cells were hybridized with either 7 or 11
      distinctly different probes. Following 46 hr of hybridization, slides were washed
      and detected using either a filter-based quantitative image processing system
      (QUIPS) developed in-house or a commercial spectral imaging system. RESULTS: The
      filter-based fluorescence microscope system is preferred for simultaneous
      detection of up to seven chromosome targets because of its high sensitivity and
      speed. However, this approach may not be applicable to interphase cells when 11
      or more targets need to be discriminated. Interferometer-based spectral imaging
      with a spectral resolution of approximately 10 nm allows labeling of chromosome
      specific DNA probes with fluorochromes having greatly overlapping emission
      spectra. This leads to increases in the number of fluorochromes or fluorochrome
      combinations available to score unambiguously chromosomes in interphase nuclei.
      CONCLUSIONS: Spectral imaging provides a significant improvement over
      conventional filter-based microscope systems for enumeration of multiple
      chromosomes in interphase nuclei, although further technical development is
      necessary in its application to embryonic blastomeres. When applied to
      preconception/preimplantation genetic diagnosis, presently available probes for
      spectral imaging are expected to detect abnormalities responsible for 70-80% of
      spontaneous abortions caused by chromosomal trisomies.

PMID- 9604770
TI  - Role of the Ped gene and apoptosis genes in control of preimplantation
      development.
AB  - PURPOSE: The properties of the mouse Ped gene and the genes that mediate
      apoptosis in mediating preimplantation embryonic survival were reviewed. METHODS:
      Preimplantation mouse oocytes and embryos were evaluated microscopically and
      biochemically for rate of development, degree of fragmentation, and gene
      expression to correlate these characteristics with embryo mortality, Biochemical
      assays included PCR for DNA analysis, RT-PCR for mRNA analysis, immuno-PCR for
      protein analysis, and TUNEL assay for assessment of apoptosis. RESULTS: Using the
      mouse as a model system we have identified a gene that controls the rate of
      development, the Ped gene. The Ped gene product is a class Ib major
      histocompatibility complex protein called the Qa-2 antigen. Research to
      understand the molecular mechanisms of Ped gene action and to identify the human
      homologue of the Ped gene is under way. We have also shown using the mouse model,
      that fragmented embryos show the morphological and biochemical characteristics of
      apoptosis. Genes in the two major gene families that regulate apoptosis, the
      caspase and Bcl-2 families, are expressed in mouse oocytes and preimplantation
      embryos. CONCLUSIONS: Preimplantation embryonic survival depends on two major
      morphological parameters: rate of development and degree of fragmentation. A fast
      rate of development and a low degree of fragmentation lead to a better chance of
      producing live offspring. Both rate of development and degree of fragmentation
      are genetically controlled, the former by the Ped gene and the latter most likely
      by genes that mediate apoptosis. It seems probable that regulation of apoptosis
      will prove to be a major mechanism that mediates oocyte and preimplantation
      embryonic survival.

PMID- 9604771
TI  - Sequence analysis of libraries from individual human blastocysts.
AB  - PURPOSE: It has recently become possible to construct cDNA libraries from
      individual human blastocysts to investigate the expression of embryonic genes in
      human preimplantation development. We have previously reported the expression of
      beta-actin, CD-59, and homeobox OCT-3 and identified almost-complete homology of
      sequences to human histone 3.1 and human ribosome protein S25. In the present
      paper, our further sequencing analysis of cDNA libraries from single human
      blastocysts is described. METHODS: cDNA libraries were constructed from 13
      blastocysts. Sequence analysis was performed in 120 clones from one of these cDNA
      libraries with fragments of 50 to 1000 bp. Their sequence identity was analyzed
      using the expressed sequence tag (EST) database. RESULTS: The presence of two
      housekeeping genes, hexokinase I and serine/threonine phosphorylase, and four
      other ESTs was demonstrated, the identity of which, with particular gene
      expression in preimplantation development, has not yet been established.
      CONCLUSIONS: The data demonstrate the usefulness of constructing cDNA libraries
      from individual human blastocysts and their values in the analysis of genetic
      expression in human preimplantation development.

PMID- 9604772
TI  - The construction of cDNA libraries from human single preimplantation embryos and
      their use in the study of gene expression during development.
AB  - PURPOSE: The construction and application of polymerase chain reaction (PCR)
      based cDNA libraries from unfertilized human oocytes and single preimplantation
      stage embryos are described. The purpose of these studies is to provide a readily
      available resource for the study of gene expression during human preimplantation
      development. METHODS: Rapid, reproducible, and efficient procedures for the
      construction of PCR-based cDNA libraries from fewer than 10 cells were first
      developed in small populations of fibroblast cells. We then constructed cDNA
      libraries from eight unfertilized oocytes and single two-cell, -4-cell, -7-cell,
      and blastocyst-stage embryos. Differential display PCR using the libraries as
      template allows the analysis of stage-specific expression of embryonic genes.
      Genomic libraries are also prepared from parental samples (cumulus cells and
      sperm) corresponding to the individual embryo generating the cDNA library.
      RESULTS: The complexities (between 10(5) and 10(6) clones) of the human embryo
      libraries indicate that they may represent the entire active gene population at
      these early stages of human development. Nucleotide sequence analyses of random
      clones showed the presence of a variety of transcripts, such as the human
      transposable element. LINE-1, Alu repeat sequences, housekeeping genes, and
      tissue-specific genes, (e.g., alpha-globin, FMR-1, and interleukin-10). Also
      present at the expected frequency are the ubiquitous cytoskeletal elements, beta
      actin, keratin-18, and alpha-tubulin. In addition to cDNAs corresponding to known
      expressed sequence tags (ESTs) in the GenBank and dbEST databases, a high
      proportion of novel sequences was also detected. Several cDNAs were detected only
      at specific stages of preimplantation development by the differential display
      analysis. CONCLUSIONS: PCR-based cDNA libraries from single human preimplantation
      embryos provide a new and important resource for the identification and study of
      novel genes or gene families. As such, they will increase our basic understanding
      of the molecular control of human development. In the clinical context, the
      libraries identify the time of onset of specific genes, and hence the diseases
      resulting from mutation of these genes, and provide information about new methods
      of preimplantation diagnosis. The molecular analysis of early gene transcription
      in human embryogenesis may be expected to lead to advances in contraception,
      assisted reproduction, and preimplantation genetic diagnosis.

PMID- 9604773
TI  - Evolutionary classification of homeodomains.
AB  - PURPOSE AND METHODS: We performed multiple comparisons between available amino
      acid (aa) sequences of homeodomain(HOM)-containing proteins from a wide spectrum
      of animals to create an evolutionary classification of the proteins. RESULTS:
      Based on results of statistical and special computational analyses of over 500
      homeodomain aa sequences (HOMs) a novel system of concepts describing complex
      structural correlations between homologous proteins is proposed. This system
      includes such notions as differentiated isofunctionality of aa, chemotype,
      stereotype, local functional motifs, gradual conservativeness of aa positions,
      and group-specific domain patterns, as well as major categories of the
      evolutionary classification of HOMs (Division, Type, Branch, Class, Family,
      Series, Variety, Sort). Using this approach, a complete structural systematics of
      HOMs belonging to proteomes of eukaryotic animals is proposed. CONCLUSIONS: The
      proposed structural classification of HOMs is in full agreement with the bulk of
      experimental data revealing complex functional similarities and differences among
      HOMs in terms of their expression patterns in developing embryos. It turn, this
      classification can provide answers regarding homology among homeodomains when
      experimental data are conflicting.

PMID- 9604774
TI  - Therapeutical approaches to transmissible spongiform encephalopathies (TSE): the
      case of amphotericin-B.

PMID- 9604775
TI  - Monoclonal antibodies in clinical applications.

PMID- 9604776
TI  - Induction of lymphomonocyte activation by HIV-1 glycoprotein gp120. Possible role
      in AIDS pathogenesis.
AB  - Dysfunction of cytokine secretion pattern has been suggested to play a central
      role in the immunopathogenesis of HIV infection. In fact a shift of T helper cell
      functions from a Th1-type to TH0- or TH2-type has been observed in HIV-1 infected
      subjects undergoing disease progression. The inhalance of cytokine network is
      accompanied by persistent activation of the immune system, impaired ability to
      mount a proper activation response (anergy), and priming to apoptosis. Extensive
      investigation during the last decade has been conducted on the influence of HIV-1
      gp120 or of its precursor gp160 on several lymphocyte and monocyte functions.
      Gp120 is able to rise intracellular calcium concentration and to induce the
      formation of inositol triphosphate, can block mitogen- or antigen-driven T cell
      activation, can induce altered cytokine production by activated PBMC
      subpopulations, determines impaired cytotoxicity and chemotactic response to
      antigens, interferes with the activity of antigen presenting cells, enhances or
      induces apoptosis, stimulates polyclonal B cell activation and induces or up
      modulates a number of cytokines, including IL-6. TNF, IL-1-alpha and -beta, IL-10
      and IL-8. Furthermore, both IFN-alpha and -gamma, as well as several markers of
      IFN activity, such as beta 2-microglobulin and neopterin, are induced in gp120
      stimulated PBMC. However, neither IL-4 (Th2-type) nor IL-2 (Th1-type), nor DNA
      synthesis are activated by gp120. On the other hand gp120-stimulated PBMC express
      increased IL-2 receptors, and can be induced by exogenous IL-2 to proliferate,
      suggesting that they are in a state of at least partial activation. According to
      this hypothesis, other activation markers, both early (such as CD69), and late
      (such as CD45RO and CD71), are induced by gp120, but this even partial activation
      does not lead to the ability of PBMC to support productive infection by HIV-1,
      unless in the presence of exogenous IL-2. The HIV-induced cytokines can influence
      HIV infection either directly, by up- or down-modulating virus replication, or
      indirectly, by modulating the expression of cellular molecules. In fact, during
      the budding process, the HIV envelope captures a number of cell membrane
      proteins, including cytokine receptors such as IL-2R, adhesion molecules such as
      LFA-1, ICAM-1, -2, HLA Class I and II, as well as cell lineage markers. Gp120
      induced cytokines, particularly IFN-gamma, upmodulate the cellular expression of
      intercellular adhesion molecules, such as ICAM-1. We have shown that the IFN
      gamma-driven increase of the expression of ICAM-1 by cells chronically infected
      with HIV-1 can be transmitted to the virus progeny, resulting in phenotypic
      alteration of the virus, and leading to the expansion of its host cell spectrum
      to CD4-negative cells expressing the appropriate ligands, i.e. LFA-1.
      Intercellular adhesion molecules are also involved in the cell-mediated
      transmission of HIV infection, and the increased ICAM-1 expression induced by IFN
      gamma determines a stimulation of the transmission of HIV from abortively
      infected endothelial cells to permissive CD4 lymphocytes. On the whole, these
      data indicate that HIV, or its soluble products such as gp120, can modify several
      PBMC functions, by inducing a number of cytokines and a partial state of immune
      activation. It is possible that the gp120-driven changes of PBMC functions are
      not only an epiphenomenon of HIV infection, but rather, it is likely that they
      can participate in the immunopathological events responsible for disease
      progression.

PMID- 9604777
TI  - Correlation between IL-12 and IL-2 blood levels in the metastatic neoplastic
      disease: a possible inhibitory feedback system regulating their secretion.
AB  - Despite the great importance of IL-2 and IL-12 in activating the anticancer
      immune response in humans, cancer-related physiopathology of their secretion
      needs to be better investigated. IL-2 blood levels have been proven to decrease
      in the advanced neoplastic disease, whereas preliminary data would suggest an
      enhanced secretion of IL-12 in metastatic cancer patients. This study was
      performed to analyze IL-2 levels in relation to those of IL-12 in metastatic
      solid neoplasms. The study included 40 untreated metastatic cancer patients.
      Serum levels of both IL-2 and IL-12 were measured by ELISA. Abnormally low blood
      levels of IL-2 and elevated values of IL-12 were observed in 16/40 and in 18/40
      patients, respectively. Moreover, patients with IL-2 deficiency showed
      significantly higher mean levels of IL-12 than patients with normal values of IL
      2. This preliminary result, by showing an increased secretion of IL-12 in
      advanced cancer patients with IL-2 endogenous deficiency, would suggest the
      existance of a possible feedback mechanism operating between macrophage release
      of IL-12 and T lymphocyte secretion of IL-2.

PMID- 9604778
TI  - Is there a correlation between tumor necrosis factor alpha and soluble p-55
      receptor plasma levels in advanced gastrointestinal cancer patients?
AB  - Studies have shown an increased spontaneous TNF alpha production, and the 24-
      rhythmicity of TNF blood concentration in patients with advanced cancer. The
      present study investigates whether diurnal rhythmicity of endogenous TNF alpha is
      associated with the induction of circulating sTNF Rp55 in advanced
      gastrointestinal neoplasm. The levels of endogenous TNF alpha and sTNF Rp55 in
      serum were measured at 8 a.m., 2 p.m., 6 p.m., 10 p.m., 2 a.m., and again at 8
      a.m. RESULTS: There is circadian rhythm in the secretion of endogenous TNF alpha
      in patients with advanced gastrointestinal cancer, however no diurnal rhythm of
      sTNF Rp55 was observed. Since it has been suggested that human tumors susceptible
      to TNF alpha may escape destruction by secreting or inducing the secretion of
      sTNF Rp55 to block the effects of TNF alpha, the possibility that the observed
      fluctuations could also reflect the complexation of a proportion of the receptor
      molecules with their ligand should be considered.

PMID- 9604779
TI  - Reactivation of a normal endogenous secretion of interleukin-2 in metastatic
      cancer patients by a chronic subcutaneous injection of interleukin-2.
AB  - It is known that advanced cancer patients may show abnormally low levels of IL-2.
      The immunotherapy with IL-2 can induce objective tumor regressions, but at
      present there are no data about the influence of a chronic exogenous IL-2
      administration on endogenous secretion of IL-2. This preliminary study was
      performed to evaluate whether a prolonged IL-2 injection may be able to correct
      an eventual IL-2 endogenous deficiency in cancer patients. The study included 10
      metastatic renal cancer patients, who underwent an immunotherapeutic cycle
      consisting of IL-2 at 6 million IU/day subcutaneously for 6 days/week for 4
      weeks. Serum levels of IL-2 evaluated on venous blood samples collected before
      and 21 days after the end of IL-2 injection. Before the onset of treatment,
      abonormally low levels of IL-2 were seen in 6/10 patients. In patients with
      response or stable disease, mean levels of IL-2 observed 21 days after IL-2 cycle
      were significantly higher than those seen before therapy, whereas no difference
      occurred in those who progressed. This preliminary study would suggest that a
      prolonged subcutaneous injection of low-dose IL-2 may correct an eventual IL-2
      endogenous deficiency in advanced cancer patients.

PMID- 9604780
TI  - Classification of retinal damage by a neural network based system.
AB  - The objective of this research is to provide an ophthalmologist with a helpful
      system, capable of classifying a degree of patients' retinal hemorrhage. The
      system is composed of four modules: (a) data acquisition module, (b) image
      Database module, (c) image processing module, (d) image classification module.
      The system was trained with a modular neural network on a set of 25 images, and
      tested on a set of 160 images. A training performance of greater than 95% was
      achieved. The classifying part of the system showed 79% recognition accuracy.
      Since the testing images were taken from independent sources, we assume that the
      system should also provide an accurate classification of other image types.

PMID- 9604781
TI  - The combination of specimen tracking with an advanced AutoLog in a laboratory
      information system.
AB  - The ability to provide timely laboratory results is an important aspect of
      quality which must be continually monitored. In order to complete all testing
      before the maximum turnaround time requirements are exceeded, laboratorians need
      to have immediate and automatic access to the location of specimens and the
      status of tests ordered on each specimen. Any such automated approach must be
      able to monitor continually the status of work in progress, while simultaneously
      linking it to a specimen tracking (history) system that allows real-time tracing
      of the path of specimens through all laboratory operations. The authors have
      greatly advanced the capabilities of the AutoLog technology and have added to it
      a tracking system that captures specimen movement with minimum user assistance.
      This has been accomplished without the need to implement total process
      automation.

PMID- 9604782
TI  - HIS/BUI: a conceptual model for bottom-up integration of hospital information
      systems.
AB  - Many successful applications of information systems have been introduced and
      implemented in hospitals. However, the integration of these applications into a
      cohesive hospital-wide information system has proved to be more complicated to
      develop and difficult to accomplish than expected. This paper introduces HIS/BUI,
      a framework for bottom-up integration of hospital information systems, and
      demonstrates its application through a real-life case scenario. The scope of the
      proposed framework is the integration of heterogeneous clinical, administrative,
      and financial information elements of a hospital into a unified system
      environment. Under the integrated architecture, all existing local applications
      are preserved and interconnected to an information hub that serves as a central
      medical and administrative data warehouse.

PMID- 9604783
TI  - Prevalence of subacute patients in acute care: results of a study of VA
      hospitals.
AB  - Subacute care is a transitional level of care for medically stable patients who
      no longer require daily diagnostic/invasive care but require more intensive care
      than is typical in a skilled care facility. A Congressionally mandated study was
      undertaken to determine the number of VA patients with subacute needs being cared
      for in acute care. InterQual, Inc. subacute care criteria were retrospectively
      applied to 858 medical and surgical admissions from 43 VA hospitals. Over one
      third contained at least one subacute day; with an average length of stay (LOS)
      of 12.7 days (SD = 12.4); of which 6.8 days were subacute. Patients with these
      admissions had significantly longer LOSs, were older, and were more likely to die
      or to be discharged to a nursing home. Diagnoses with subacute days included
      COPD, pneumonia, joint replacement, and cellulitis. Future studies should develop
      clinical pathways to prospectively manage admissions with subacute needs and then
      evaluate their effectiveness.

PMID- 9604784
TI  - Community-based medical systems advancement in a hospital-primary health care
      centre in Crete, Greece: concepts, methods, and the new role of the general
      practitioner.
AB  - Modern health systems research and development emphasize the transition from
      hospital to primary health care. Importantly, this transition is projected to be
      coordinated and interactive, as facilitated, e.g., by improved information
      systems and collaboration between the involved parties, including Universities
      and health authorities. An ideal combination of this might accordingly be offered
      by a synthesis of a basic hospital and primary health care center in an area of
      suitable site, size, and structure. We believe that our institution, Nosokomion
      Neapolis, in; the moderate-size Cretan township of Neapolis (New-city) offers an
      interesting model example of this, because of its affiliation with the University
      of Heraklion and its international and EU-supported project status. In the
      present report we want to emphasize the elements that are particularly well
      suited and manageable and in many ways both opportunistic and conscientious "back
      to the future" instances of a successful Hospital/Primary Health Care
      integration. Specifically, we think that the advantages in local area
      epidemiology, prevention, and quality assurance are apparent, and nurture a-
      rather renewed that new-role of the general practitioner as both a holistic
      population doctor and a health systems researcher for the year 2,000 and beyond.

PMID- 9604785
TI  - An expert system for assigning patients into clinical trials based on Bayesian
      networks.
AB  - Assigning patients into clinical trials is a knowledge and data intensive task.
      Eligibility determination for entry into a clinical trial is based upon specific
      inclusion and exclusion criteria. This paper investigates the use of an excerpt
      system to assist the physician through this task. This expert system uses
      Bayesian networks, a probabilistic method that can take advantage of pre-existing
      statistical knowledge. The paper also describes the feasibility of such a system
      by presenting the implementation of three clinical protocols. The experimental
      results reveal that the approach is feasible. The system gives correct
      eligibility scores when all evidence is available but also predicts eligibility
      when there is missing evidence. The system directs the physician to the protocols
      the patient is most eligible for, according to the current evidence. The system
      has the ability of learning its prior and conditional probabilities (expert
      knowledge) from training examples.

PMID- 9604786
TI  - Autoimmunity and AIDS. A commentary.

PMID- 9604787
TI  - Patterns of delivery of radiation therapy in an inner-city population of head and
      neck cancer patients: an analysis of compliance and end results.
AB  - A retrospective analysis of survival rate of patients treated for head and neck
      cancers in a radiation oncology department at an innercity hospital (UMDNJ,
      Newark, NJ) was performed. Eligible patients received either postoperative or
      definitive radiation therapy and had no distant metastases. The records of
      patients treated from 1984-1989 were screened and 78 met the above criteria.
      Total dose of radiation, fraction size, number of fractions given, and overall
      duration of treatment were determined. Tumor registry data was used to evaluate
      patient status. Two patients who died prior to completing radiation treatments
      were excluded and seven patients were lost to follow up. Therefore, the outcomes
      and treatments of 69 patients were analyzed. There were two categories of
      noncompliant patients, those whose treatment duration was in excess of 20% of the
      prescription, and those whose treatments were discontinued against medical
      advice. The overall five year survival of the compliant group was 38%, and 12%
      for the noncompliant group (p < 0.05). The mean survival time for the compliant
      group was 24.2 months and 12.6 months for the noncompliant group (p < 0.05).
      Forty-seven per cent of the patients were compliant. Compliant rates for men and
      women were 46% and 48%, respectively. African-Americans, who made up 71% of the
      patients analyzed, had a compliance rate of 45%. Caucasians, who made up 22%, had
      a compliance rate of 47%. The stage at presentation, and therefore prognosis, did
      not alter compliance rates. Sixty-nine per cent of the patients analyzed had
      stage III or stage IV disease. This patient group had a compliance rate of 48%,
      which did not statistically differ from the earlier stage patient group which had
      a compliance rate of 54%. The length of patient survival from head and neck
      cancer is related to compliance to radiation treatment. Compliance appears to be
      directly related to better overall survival and mean survival time. Compliance to
      treatment does not seem to depend on patient sex, race, or prognosis.

PMID- 9604788
TI  - Expression of cyclins D1 and E in human colon adenocarcinomas.
AB  - Cyclins D1 and E play critical roles in the progression of cells through the G1
      phase of the cell cycle. Amplification and/or overexpression of the cyclin D1
      gene and aberrant expression of cyclin E have been described in several forms of
      human cancer. In the present study, we examined the expression of these two genes
      by Western, Northern and Southern blot analyses in a series of primary human
      colon carcinomas of various stages and degrees of differentiation and in paired
      adjacent normal mucosa samples, and also in a series of human colon carcinoma
      cell lines. About 50% of the colon carcinomas displayed a two to five fold
      increase in the expression of cyclin D1 mRNA and protein, when compared with the
      paired normal mucosa samples. Six out of eight carcinomas examined showed a four
      to nine fold increase in cyclin E mRNA and about 50% of the carcinomas displayed
      a two to three fold increase in cyclin E protein. Low molecular weight cyclin E
      related proteins were observed in four out of ten carcinomas. These changes in
      cyclins D1 and E occurred in both early and late stage tumors. Three of the six
      cell lines examined displayed a high expression of cyclin D1 mRNA and protein. A
      very high level of cyclin E mRNA expression was seen in HCT116 cells and this was
      associated with the presence of low molecular weight cyclin E-related proteins.
      None of the primary colon carcinomas nor the six cell lines examined displayed
      amplification of either the cyclin D1 or cyclin E genes. Thus, an aberrant
      expression of both cyclins D1 and E occurs in a significant fraction of human
      colon carcinomas.

PMID- 9604789
TI  - Serum beta-2-microglobulin in patients with multiple myeloma treated with alpha
      interferon.
AB  - In ten patients with multiple myeloma (MM), serum beta-2-microglobulin (B2M)
      levels were monitored in order to clarify the influence of alpha interferon (IFN)
      administration. Despite decreases in M-protein and the absence of renal
      dysfunction, the levels of serum B2M were sustained above those prior to
      melphalan-prednisolone and IFN therapy in seven patients with MM for six months.
      Serum B2M did not increase in ten patients with MM treated only by melphalan
      prednisolone. Furthermore, serum B2M levels in a patient who achieved a complete
      response were sustained above her prior level and returned to normal after
      cession of IFN therapy. Our study suggests that the serum B2M level is increased
      by treatment with IFN, and does not prove the condition of the disease.

PMID- 9604790
TI  - Reduced serum T3 level in a patient with nodular goiter and cardiac myxoma.
AB  - We report the unusual case of an 87-year-old woman with cardiac myxoma and
      adenomatous goiter. She exhibited slight elevations of serum interleukin-6 (IL
      6), but levels of thyroid hormones such as T3, free T3 and free T4 were all
      abnormally low. Interleukin-6 may potentiate the alteration of thyroid
      metabolism.

PMID- 9604791
TI  - Interferon-alpha therapy alters glucose metabolism in patients with chronic
      hepatitis B.
AB  - Although interferon alpha (IFN alpha) has been widely used for therapy of chronic
      hepatitis B, no prospective studies have examined the changes in glucose
      metabolism during IFN alpha therapy in patients with chronic hepatitis B. To
      study the effects of IFN alpha on glucose metabolism in patients with chronic
      hepatitis B, we prospectively examined glucose tolerance in 11 patients with
      chronic hepatitis B before and four weeks after the start of IFN alpha therapy.
      Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities
      were improved after the therapy, compared with before (p < 0.05, respectively).
      The levels of blood sugar at 30 min and 90 min in a 75 g-oral glucose tolerance
      test (OGGT), fasting immunoreactive insulin (IRI) and IRI at 90 min in a 75 g
      OGTT were decreased (p < 0.05, respectively). Response patterns in 75 g-OGGT
      before therapy were two patients with a normal pattern, eight with a borderline
      pattern and one with a diabetic pattern. However, those after therapy were
      changed to six with a normal pattern, three with a borderline pattern and one
      with a diabetic pattern. The results of the present study suggest that IFN alpha
      therapy improves hepatic necro-inflammation in patients with chronic hepatitis B,
      and that IFN alpha alters glucose metabolism in these patients.

PMID- 9604792
TI  - Changes in glucose tolerance after interferon-alpha therapy in patients with
      chronic hepatitis C.
AB  - Interferon alpha (IFN alpha) has been widely used as therapy for chronic
      hepatitis C. However, changes in glucose metabolism during IFN alpha therapy in
      patients with chronic hepatitis C remain unknown. To study the effects of IFN
      alpha on glucose tolerance in patients with chronic hepatitis C, we prospectively
      examined glucose tolerance in 15 patients with chronic hepatitis C before and
      four weeks after the start of IFN alpha therapy. Serum bilirubin, albumin,
      aspartate aminotransferase (AST) and alanine aminotransferase (ALT) improved
      after the therapy compared with before (p < 0.05, respectively), while levels of
      fasting blood sugar, blood sugar at 30 min in 75 g-oral glucose tolerance test
      (OGGT) and fasting immunoreactive insulin (IRI) decreased (p < 0.05,
      respectively); insulinogenic index (II) also increased (p < 0.05). Response
      patterns in 75 g OGGT before therapy were: four patients in normal pattern, five
      in a borderline pattern and four in a diabetic pattern, whereas those after
      therapy were changed to four in a normal pattern, and eight in a borderline
      pattern. Changes in AST between before and after therapy were correlated with
      those in blood glucose at 30 min in a 75 g-OGGT (r = +0.648, p = 0.042). Although
      interferons have been reported to impair glucose tolerance in viral infection,
      the results of the present study indicate that hepatic functional recovery may be
      associated with improved glucose tolerance in patients with chronic hepatitis C
      treated with IFN alpha.

PMID- 9604794
TI  - Missed opportunities: ALT and anti-HBc as surrogate tests for hepatitis.
AB  - ALT and anti-HBc came into use in the US as surrogate tests for non-A, non-B
      hepatitis by 1986-1987, generally using cutoffs at 50-60 IU/L. We studied the
      usefulness of anti-HBc, and of ALT at different cutoffs as surrogate tests for
      hepatitis C virus, recording and analyzing the ALT, anti-HBc, HBsAg, and RIBA
      results of 175 non-autologous blood donations in 1993 and 1994 that had positive
      second generation screening tests for anti-HCV. ALT levels of 1014 blood
      donations also were studied. Only 93 of 175 anti-HCV-positive donations were RIBA
      positive. Of these, anti-HBc would have excluded 23%, an ALT cutoff at 60 IU/L
      would have excluded 42% and an ALT cutoff at 40 IU/L would have excluded 70%
      (plus 5.6% of all donations). Both tests together would have been better than
      either alone. No tests for HBsAg were positive. ALT and anti-HBc clearly were
      useful surrogate tests for hepatitis C. If they had been used sooner and with
      lower ALT cutoffs, many people would have avoided post-transfusion hepatitis in
      the years before anti-HCV testing was available.

PMID- 9604793
TI  - Autoimmune hepatitis types IIa and IV in young men.
AB  - Two young men with autoimmune hepatitis types IIa and IV are reported here. These
      rare types of the disease could be diagnosed by using the diagnostic criteria for
      scoring of autoimmune hepatitis established by the International Group.

PMID- 9604795
TI  - Effect of fosinopril sodium on early carotid atherosclerosis in diabetic patients
      with hypertension.
AB  - An increased thickness of the carotid artery wall is thought to be a sign of
      early atherosclerosis. We have investigated the effects of fosinopril sodium in
      asymptomatic diabetic hypertensive subjects on the 12-month progression of
      arterial wall thickness. Forty non-insulin-dependent diabetics with hypertension
      and without hyperlipidemia were studied. After a 4-week run-in-diet phase, oral
      fosinopril sodium was administered (20 mg once daily) to 20 patients randomly
      selected, while 20 subjects were treated only with diet. The two groups were
      matched for age, sex, body mass index (BMI), duration of diabetes and glycemic
      control. Arterial wall thickness was measured as the mean of the maximum intimal
      media thickness (IMT) in 16 carotid segments by B-mode ultrasound. The IMT
      increase over 12 months was 4.3% in the fosinopril sodium group vs 15.1% in
      subjects with diet. We conclude that fosinopril sodium treatment may be useful in
      decreasing the progression rate.

PMID- 9604796
TI  - Activated protein C resistance assay as a screening test for thromboembolic
      disposition.
AB  - An activated partial thromboplastin time (APTT) based method was developed to
      determine the anticoagulant response in patient plasma to added purified
      activated protein C (APC). On the other hand, Bertina et al. (1994) reported that
      one point mutation of amino acid 506 in the factor V was observed in such APC
      resistance patients. APC resistance for blood samples with known abnormal
      findings on the coagulation test also may be determined. Coagmaster II for the
      APTT assay system (Sankyo, Tokyo, Japan) was employed. The APC resistance assay
      system was a useful reagent as a screening test for lupus anticoagulant (LA), in
      addition to APC resistance.

PMID- 9604797
TI  - Leg ulceration and the cholesterol embolus.
AB  - An important and frequently overlooked cause of leg ulcers are cholesterol
      emboli. A 79-year-old woman with a non-healing leg ulcer is described. The
      diagnosis of cholesterol embolism was made with the aid of a deep biopsy of the
      ulcer and serial sectioning of the specimen. This report serves to illustrate the
      importance of considering cholesterol embolism when evaluating a chronic leg
      ulcer, and the diagnostic value of proper biopsy techniques.

PMID- 9604798
TI  - A survey regarding the factors that influence bone mineral density among female
      high school students.
AB  - In our study of the relationship between bone mineral density (BMD) and physical
      constitution (height and weight) of the female students, those weighing more than
      the Japanese national average displayed higher BMD values compared with students
      weighing less than the national average, indicating significant differences.
      Those students who indicated the onset of the menstrual function at 10-11 years
      of age, exhibited significantly higher BMD values than students who had not yet
      begun menarche. At the same time, students having higher BMD values, considered
      themselves to be tending toward obesity because of their heavier weight, and were
      pursuing a tendency toward following weight-reduction diets. Although one can
      understand the mentality of adolescent female students being conscious of better
      physical proportions, they need suitable advice regarding adequate nutrition.

PMID- 9604799
TI  - Effects of TNF-alpha injection into the ovary on blood progesterone concentration
      in pseudopregnant rabbits.
AB  - To examine the effects of TNF-alpha on luteal functions, TNF-alpha was injected
      into the ovary of rabbits on the 7th day of pseudopregnancy (Day 7). The animals
      were laparotomized under general anesthesia, and 1 x 10(4) IU TNF-alpha dissolved
      in PBS was injected into the ovary. On Days 8 and 10, the blood progesterone (P)
      concentration was determined. The mean blood P level was 10.31 ng before the
      administration of TNF-alpha on Day 7. On Day 8, the mean blood P level was 11.22
      ng in the control group, while it was markedly reduced to 1.29 ng in the TNF
      alpha administration group. On Day 10, the mean blood P level was 6.80 ng in the
      control group and 5.49 ng in the TNF-alpha group. These results suggest that the
      capacity for P secretion of the corpus luteum, which reached a degenerative stage
      by TNF-alpha administration, can be recovered.

PMID- 9604800
TI  - The clinical spectrum of the primary hyperoxalurias and their treatment.

PMID- 9604801
TI  - The molecular basis of alanine: glyoxylate aminotransferase mistargeting: the
      most common single cause of primary hyperoxaluria type 1.
AB  - The autosomal recessive disease primary hyperoxaluria type 1 (PH1) is caused by a
      deficiency of the liver-specific intermediary metabolic enzyme alanine:glyoxylate
      aminotransferase (AGT). In a third of all Caucasian PH1 patients, disease in
      caused by an unparalleled intracellular phenomenon in which AGT is mistargeted
      from one group of intracellular organelles (the peroxisomes) to another (the
      mitochondria) where it is unable to work properly. The aberrant localisation of
      AGT in PH1 is caused by the combination of a common Pro 11-->Leu amino acid
      polymorphism which generates a functionally weak mitochondrial targeting signal
      (MTS) and a rare Gly170-->Arg mutation which in combination with the Pro11-->Leu
      polymorphism enhances the functional efficiency of this MTS by slowing AGT
      folding and dimerization. Elucidation of the molecular basis of AGT mistargeting
      not only provides an explanation for the mode of action of the most common
      mutation found in PH1, but also highlights the different structural requirements
      for protein import into peroxisomes and mitochondria.

PMID- 9604802
TI  - Experience in prenatal diagnosis of primary hyperoxaluria type 1.
AB  - Prenatal diagnosis of primary hyperoxaluria type 1 (PH1) using DNA-based
      techniques has been performed in 22 pregnancies from 21 families to date. The
      outcome of these diagnoses were: 2 affected, 14 carriers and 4 normal fetuses. In
      2 families, only partially informative at the time of testing, a clear diagnosis
      could not be made and in one of these cases the presence of disease could not be
      excluded. The methods, which use a combination of linked polymorphisms and
      detection of the two most common mutations, have a diagnostic accuracy of > 99%
      and can be performed in the first trimester of pregnancy.

PMID- 9604803
TI  - Identification of new mutations in primary hyperoxaluria type 1 (PH1).
AB  - Primary hyperoxaluria type 1 (PH1) is caused by deficiency of the hepatic
      peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT). The AGXT gene,
      which codes for the 392 amino acid protein, has been mapped to chromosome 2q37.3.
      In order to identify new mutations in the AGXT gene we studied 79 PH1 patients
      using single strand conformation polymorphism analysis. In addition to a cluster
      of new mutations in exon 7 we report five novel mutations in exons 2, 4, 5, 9 and
      10. These are T444C, G640A, G690A, 1008-1010delGCG and G1171A. These five new
      mutations contribute to our knowledge of the AGXT gene. Their possible
      consequences for PH1 phenotype and enzyme activity are discussed.

PMID- 9604804
TI  - Molecular analysis of the AGXT gene in Italian patients with primary
      hyperoxaluria type 1 (PH1).
AB  - Specimens were collected from 22 Italian patients with primary hyperoxaluria type
      1 (PH1). Ten of them had already been analyzed by molecular biology. To clarify
      the molecular characteristics of the AGXT gene disease responsible for PH1, DNA
      samples were examined for known mutations by hybridisation of PCR products with
      Sequence Specific Oligonucleotides (PCR-SSO). We planned to identify new
      mutations of the AGXT gene by heteroduplex analysis followed by direct
      sequencing. We had already standardized a) the conditions for the amplification
      of the 11 exons of AGXT, b) the PCR-SSO technique and c) the heteroduplex
      analysis of amplified products. Preliminary results demonstrated that the AGXT
      mutations described in previous studies were found only in 40% of the examined
      Italian patients with PH1. The remaining 60% of mutations should be characterised
      in future studies.

PMID- 9604805
TI  - Biochemical approach to diagnosis and differentiation of primary hyperoxalurias:
      an update.
AB  - The hyperoxaluria syndromes can be differentiated by the assessment of associated
      abnormalities in generation and urine excretion of metabolically related
      molecules. Based on the experience gained in our laboratory during the last
      decade, we have developed a comprehensive diagnostic work-up, which includes
      measurements of oxalate, glycolate and L-glycerate in plasma, urine and dialysis
      fluids, and an assay for AGT activity on liver biopsy. The availability of
      reliable assays for each of these parameters is indispensable for the recognition
      and differentiation of hyperoxalurias. Patients suspected to have abnormalities
      in oxalate metabolism are first screened by analysing spot urines and serum, and
      subsequently are subjected to more extensive studies using properly pre-treated
      blood samples and 24-hour urine collection. AGT activity, in the case of PH1, is
      assayed on few milligrams liver specimen by using a sensitive chromatographic
      procedure. Pertinent biochemistries will also assist in the long-term medical
      follow-up of these patients and in view of the choice of renal replacement or
      transplantation strategies.

PMID- 9604806
TI  - Primary hyperoxaluria type 2: enzymology.
AB  - Deficiency of the enzyme D-glycerate dehydrogenase (D-GDH) which also has
      glyoxylate reductase (GR) activity, is believed to be the underlying cause of
      primary hyperoxaluria type 2 (PH2). We have established the reaction kinetics of
      this enzyme in human liver and using these parameters have developed a microassay
      for the measurement of D-GDH and GR on needle liver biopsies obtained from
      patients with suspected primary hyperoxaluria. Tissue distribution studies of the
      two enzyme activities suggest that more than one enzyme with D-GDH activity is
      present in human tissues and the one with associated GR activity is mainly
      confined to the liver. The clinical significance of these findings for diagnosis
      and treatment is discussed.

PMID- 9604807
TI  - Pharmacological approaches in the treatment of primary hyperoxaluria.
AB  - Drug therapy receives scant attention as a treatment mode for primary
      hyperoxaluria (PH). Currently, pyridoxine is the only drug in the arsenal and
      only a minority of PH1 patients respond to it. In this report a pathway
      describing the synthesis of glyoxylate, the major precursor of oxalate, is
      proposed and potential drugs that may be effective in inhibiting hepatic oxalate
      synthesis are discussed. One of these, (L)-oxothiazolidine-4-carboxylate (OTZ),
      is currently undergoing evaluation in a Phase II clinical trial. It is suggested
      that an ideal drug may be an antisense oligonucleotide that blocks the expression
      of glycolate oxidase, a key enzyme in hepatic oxalate synthesis.

PMID- 9604808
TI  - The results of combined liver/kidney transplantation for primary hyperoxaluria
      (PH1) 1984-1997. The European PH1 transplant registry report. European PH1
      Transplantation Study Group.
AB  - Between 1984 and 1987 thirty European Centres reported 87 liver transplants
      (usually in combination with a renal transplant) in 80 patients with an
      underlying diagnosis of Primary Hyperoxaluria (PH1). Mean age of onset of first
      symptoms was 5.4 +/- 7.9 years with a mean delay to diagnosis of 4.2 +/- 6.3
      years. The mean age at transplantation was 17.3 +/- 11.7 years with a mean
      duration of dialysis of 3.1 +/- 3.1 years. There was a family history in 43% of
      cases. Following transplantation one, two and five year patient survival rates
      were 88%, 80% and 72% and graft survival rates were 82%, 78% and 62% at the same
      time intervals. Patients who had been on dialysis for less than two years at the
      time of transplant were more likely to be assessed as being in good general
      condition at the time of transplantation and had better survival than those who
      had been on dialysis for longer time periods and carne to transplantation with
      evidence of marked systemic oxalosis. Combined liver/kidney transplantation
      appears to give excellent results in patients with PH1 although the results are
      poor when transplantation is delayed until advanced systemic oxalosis has
      developed. The registry will continue to collect and analyse data from patients
      undergoing liver/kidney grafting for PH1.

PMID- 9604809
TI  - Recent data on results of isolated kidney or combined kidney/liver
      transplantation in the U.S.A. for primary hyperoxaluria.
AB  - Renal transplant for primary hyperoxaluria (PH) has been problematic. K/L-Tx is
      used almost exclusively in Europe. In USRDS data 235 patients had PH diagnosed at
      ESRD, another 47 found later. Since 1994, there were 176, since our modern
      management protocol, 96 under age 55. Of 82 non-K/L-Tx, 40 of 49 were alive after
      K-Tx, 14 of 33 without Tx. By lifetable analysis, survival was better for K-Tx
      (85% at 5 yrs, 75% at 10 yrs) than for non-Tx patients (40% at 5 yrs, 75% at 10
      yrs) (P < .001). First Tx graft lifetable survival was 70% for LRD, 50% for CAD
      Tx at 3 yrs, both 40-45% at 5 years (N.S.). Twenty-eight K/L-Tx PH patients from
      the UNOS database had projected survival 50% at 5 yrs. Overall, transplant is
      better for patient survival than no transplant. While curative, K/L-Tx still has
      considerable risk in the U.S., but could follow failed K-Tx. Confirmation of PH
      and ruling out B6 sensitivity must precede K/L-Tx to justify its risk. Post Tx
      management for K/L-Tx must follow protocols developed to prevent oxalate
      recurrence for K-Tx.

PMID- 9604810
TI  - Preemptive liver transplantation in primary hyperoxaluria type 1: timing and
      preliminary results.
AB  - Preemptive isolated liver transplantation (PLTX) can cure the metabolic defect in
      primary hyperoxaluria type 1 (PH1) but there are no uniformally accepted
      recommendations concerning the timing of this transplantation procedure. We have
      performed PLTX successfully in 4 children (age 3-9 years) with PH1 with no
      mortality or morbidity due to the transplantation procedure. Plasma and urinary
      oxalate levels normalised rapidly and renal function remained stable including
      one patient with advanced chronic renal failure who showed a stable course for
      more than 24 months. Although treatment must be individualised in this severe
      metabolic disorder and PLTX has to be viewed as invasive procedure, we feel PLTX
      should be offered and discussed not too late in the treatment of PH1 to prevent
      or at least delay the progression to end stage renal disease and systemic
      oxalosis.

PMID- 9604811
TI  - Pyridoxine-responsive PH1: treatment.
AB  - Owing to the rarity of PH, the efficacy of pyridoxine therapy has only been
      tested in very small series of patients. From two recent reports including 18
      patients, 50% of patients would be unresponsive to pyridoxine whereas oxaluria
      would be normalized in 20% of patients and somewhat reduced-but not to normal
      level-in the remaining 30%. In a few aneodotical cases pyridoxine administration
      was reported to improve kidney function in patients with renal failure secondary
      to hyperoxaluria. It is reminded that megadoses of pyridoxine (0.5 to 6 g daily)
      may induce severe sensory neuropathy.

PMID- 9604812
TI  - Unusual morphology of calcium oxalate calculi in primary hyperoxaluria.
AB  - Primary hyperoxaluria (PH) is a severe inherited disease induced by an enzymatic
      deficiency responsible for high endogenous production of oxalate. Oxalate ions
      are excreted by the kidney where they can form an insoluble salt with calcium
      ions, thus inducing urinary stones, crystal deposition in the tubular lumen and
      renal parenchyma leading to nephrocalcinosis and renal failure. Eighty-seven
      calculi from 63 PH patients with primary hyperoxaluria were analyzed and compared
      to 24,130 calculi from unselected consecutive stone formers referred to our
      laboratory between January 1977 and December 1996. All stones were analyzed
      according to a protocol including morphological examination of both surface and
      cross-section, and sequential infrared identification of the crystalline phases.
      A typical aspect of both surface and section corresponding to morphological type
      Ic according to our proposed classification (Daudon et al. Scanning Microsc 1993,
      7:1081-1106) was observed in all patients but two whereas only two type Ic stones
      were observed among patients without primary hyperoxaluria. The latter two
      patients suffered from severe inflammatory bowel disease and developed heavy
      hyperoxaluria following extensive ileal resection. We conclude that evidence of
      type Ic morphology is a simple, cheap and fast tool to detect diseases with heavy
      hyperoxaluria such as primary hyperoxaluria.

PMID- 9604813
TI  - Clinical expression and long-term outcomes of primary hyperoxaluria types 1 and
      2.
AB  - Primary hyperoxaluria, types 1 and 2, are rare disorders. Much of the information
      in the literature has been derived from case reports and data registries limited
      to patients requiring dialysis and/or transplantation. We present a single-center
      experience of 42 patients and 437 patient years of clinical experience with
      primary hyperoxaluria. Median age at onset of symptoms for patients with type 1
      PH was 9 years, type 2 15.7 years. Sixty-four percent of the patients were less
      than 15 years of age at onset of symptoms. There was no correlation between urine
      oxalate excretion rates and age at onset of symptoms. Stone forming activity was
      greater in patients with type 1 PH than type 2. Ten patients presented initially
      with ESRD, and an additional seven developed ESRD during the course of follow-up.
      ESRD occurred in 54 percent of the patients with type 1 and 12 percent of
      patients with type 2 PH. Eight patients received nine renal allografts, five
      patients received combined kidney/liver transplants, and one patient received a
      hepatic allograft only. Ten of the transplanted patients were surviving at the
      time of the most recent follow up. Eight of them have functioning renal grafts
      and four have functioning hepatic grafts. There have been no deaths since 1988
      among the 32 patients followed since that time. These data may suggest a broad
      range of clinical expression of primary hyperoxaluria. With current management
      strategies, outcomes are more favorable than has been reflected in previous
      literature.

PMID- 9604814
TI  - Oxalate uptake in fetal rat myoblasts.
AB  - Oxalate uptake was studied in fetal rat myoblasts to attempt to define the
      characteristics of oxalate transport in myocardial cells. Oxalate uptake was
      found to be time, temperature and pH dependent and was inhibited by metabolic
      inhibitors (Dinitrophenol and iodoacetamide). Inhibition of oxalate uptake by
      4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) suggested transport by
      an anion exchange mechanism. Both chloride and sulfate inhibited oxalate uptake
      suggesting competition by both ions for a combined transporter. Although medium
      calcium concentration and calcium ionophores had no effect on oxalate uptake, the
      calcium channel blocker, nifedipine, significantly decreased oxalate uptake.
      Diacylglycerol (DAG) stimulated oxalate uptake, while forskolin had no effect.
      These studies suggest that myocardial cells transport oxalate by a mechanism
      similar to that described in renal epithelial cells. The uptake of oxalate by
      myocardial cells raises questions about the physiologic role of oxalate in
      myocardial cells and the mechanism of cardiac problems in primary hyperoxaluria.

PMID- 9604815
TI  - Mechanisms of oxalate cellular transport in idiopathic calcium nephrolithiasis.

PMID- 9604816
TI  - Oxalate and calcium oxalate crystals are injurious to renal epithelial cells:
      results of in vivo and in vitro studies.
AB  - Calcium oxalate (CaOx) nephrolithiasis was induced in male Sprague-Dawley rats by
      administration of 0.75% ethylene glycol. Urinary excretion of lactate
      dehydrogenase (LDH) was used as a marker of cellular injury. Lipid peroxides
      (LP), as marker for free radical injury, were measured as malondialdehyde (MDA)
      in urine and the kidneys. Urinary oxalate (Ox), LDH, LP, CaOx crystals, and renal
      LP and CaOx crystal deposits were examined on day 0, 5, 30 and 60 of the
      experiment. There were significant differences between control and experimental
      rats in all the parameters except LDH which did not show a significant increase
      after 15 days. Subconfluent cultures of MDCK and LLCPK1 cells were exposed to
      various concentrations of oxalate and/or 500 fg/ml CaOx crystals. Cell viability
      was assayed by trypan blue exclusion, cellular injury was determined by measuring
      LDH in the media, and free radical injury was measured as MDA contents of the
      cells. On exposure to both Ox and/or CaOx crystals trypan blue exclusion
      decreased and LDH and MDA increased significantly in both tissue cultures. LLC
      PK1 appeared more sensitive. The results indicate that both oxalate and calcium
      oxalate crystals are injurious to renal epithelial cells in the kidneys as well
      as in culture.

PMID- 9604817
TI  - Hyperoxaluria in patients with idiopathic calcium nephrolithiasis.
AB  - We studied 476 patients with idiopathic renal calcium stone disease (286 M, 190
      F) while they ate their customary diets. Each subject collected a 24-hour urine
      sample and completed a dietary diary for a 3-day period. Daily urinary oxalate
      excretion (M 0.24 +/- 0.15 mg/dl, F 0.23 +/- 0.15 mg/dl) and nutrient intake
      values were calculated and multiple regression analyses were performed. Daily
      urinary oxalate excretion was significantly (p < 0.001) related to urinary volume
      (R = 0.24), vitamin C intake (R = 0.33) and body mass index (R = 0.37) and
      inversely related to calcium intake (R = -0.35). We conclude that urinary oxalate
      reflects endogenous oxalate production, presumably related to body size, but also
      intestinal absorption of oxalate, related to dietary intake and to the effect of
      dietary calcium intake which reduces intestinal oxalate absorption.

PMID- 9604818
TI  - A serum oxalate assay using chemiluminescence detection, adapted to a paediatric
      population.

PMID- 9604819
TI  - Eye movements: pathophysiology, examination and clinical importance.
AB  - The ocular motor system finds, focuses, fixates and follows objects to ensure
      optimal vision as we move through our environment. To see clearly, images must be
      held steady on the retina. If images move across the retina at more than a few
      degrees per second they appear blurred. Thus, one function of eye movements is to
      hold images of the world steady on the retina, and this is accomplished by the
      gaze-holding mechanisms--fixation, vestibular and optokinetic. Visual acuity is
      best at the fovea, and so a second function of eye movements is to change the
      line of sight so that the image of an object of interest is brought to and held
      close to this part of the retina. This second group of eye movements, the gaze
      shifting mechanisms, comprise saccades, smooth pursuit and vergence. The net
      result of gaze-holding and gaze-shifting mechanisms working properly together is
      clear, binocular vision. Conversely, if these movements are not working together,
      our view of the world becomes compromised by double-vision, blurred vision or
      oscillopsia, the sensation that the seen environment is jumping. The anatomic
      substrate for each functional class of eye movements is now well defined. This
      means that specific abnormalities on the eye movement examination may provide
      clues to the underlying pathology, and suggest strategies for treatment of a
      variety of neurological disorders.

PMID- 9604820
TI  - Biological and behavioral correlates of stroke and depression.
AB  - Stroke is the third leading cause of death in the United States. Depression
      following stroke is a major problem as it can increase the morbidity. A greater
      understanding of the biological and behavioral correlates of stroke and
      depression enhances the practice of neuroscience nurses interacting with stroke
      patients. There is an ongoing debate as to whether patients with left or right
      sided lesions have higher rates of depression. Current research suggests
      neurochemical correlates of stroke and depression; however, behavioral problems
      do relate, to a large extent, to the different behavioral manifestations seen in
      left and right-sided lesions. Furthermore, these biological and behavioral
      correlates have important implications for assessment and treatment modalities.

PMID- 9604821
TI  - Patient management of cerebral origin spasticity with intrathecal baclofen.
AB  - Controlled, continuous intrathecal infusion of baclofen injection relieves severe
      spasticity for a wide range of patients. This therapy has become a standard
      treatment option in spasticity management programs. Multidisciplinary teams,
      coordinated by an experienced neuroscience practitioner, provide treatment in
      five phases. Experience from clinical trials and commercial use of this treatment
      provides a guide for others who are initiating this therapy at their facility.
      Further prospective research is needed to accurately determine best clinical
      practice guidelines for cost effective use of this therapy.

PMID- 9604822
TI  - Quality of life: effect of reduced spasticity from intrathecal baclofen.
AB  - Severe, uncontrolled spasticity resulting from spinal cord injury (SCI) and
      multiple sclerosis (MS) can have a profound effect on the patient's ability to
      function and thus, their quality of life. Spasticity can be dramatically reduced
      by the continuous infusion of baclofen into the lumbar subarachnoid space using a
      drug delivery system. The aim of this study was to explore the effect of reduced
      spasticity on quality of life using intrathecal baclofen therapy. Twenty-five
      patients with intractable spasticity treated with intrathecal baclofen
      participated in this prospective study. Spasticity was measured using the
      Ashworth and spasm scales. Quality of life was measured using the Ferrans and
      Powers Quality of Life Index (QLI) and the Sickness Impact Profile (SIP). The
      mean spasm score decreased significantly from 2.6 at baseline to 0.5 after one
      year (Friedman test; p = 0.000017). The mean Ashworth score decreased
      significantly from 3.78 at baseline to 1.48 after one year, (Friedman test; p =
      0.00000014). Though total QLI scores were not significantly different when
      comparing baseline with one year, the SIP revealed significant changes in the
      total score as well as the physical and psychosocial subscales. It is likely the
      QLI did not demonstrate improvement in quality of life due to the emphasis of
      this tool on nonphysical domains. A qualitative analysis of two open-ended
      questions revealed positive statements about the change in quality of life when
      spasticity is well-controlled. Measuring changes in quality of life after
      specific interventions is a difficult task, requiring an accurate operational
      definition of the concept and valid instruments for measurement.

PMID- 9604823
TI  - Serum phenytoin levels of patients on gastrostomy tube feeding.
AB  - Serum phenytoin levels of two groups of brain-injured patients on gastrostomy
      tube (GT) feeding were retrospectively examined. In the first group (group C =
      clamped, n = 13), GT was clamped for one hour after the phenytoin dose (2-3 doses
      per day), and in the second group (group NC = not clamped, n = 9) GT feedings
      were continued without interruption. Mean +/- SD of the serum phenytoin levels
      was 14.4 +/- 4.7 micrograms/ml for group C, and 9.2 +/- 6.8 micrograms/ml for
      group NC. When serum phenytoin levels were adjusted for decreased serum albumin
      levels, the results were 19.8 +/- 6.4 micrograms/ml for group C and 11.7 +/- 7.9
      micrograms/ml for group NC. Statistical analysis showed a significant difference
      between the means in both the phenytoin and adjusted phenytoin levels between the
      two groups (p < 0.05). No significant difference was found in phenytoin dosage
      per kg of body weight, protein intakes, calcium, magnesium and sodium per 24
      hours between the means for the two groups. Results of this study suggest that
      clamping the GT for one hour after the phenytoin dose results in higher serum
      levels of the drug.

PMID- 9604824
TI  - Spirituality: the missing link.
AB  - Comprehensive nursing care for the patient is a goal of nursing. Attending to the
      spiritual needs of a patient is an issue that nurses should identify as a need
      and yet may be overlooked. Research regarding spirituality and the reasons for
      nurses intervention or nonintervention are examined. Presented along with the
      research are methods, questions and interventions the practitioner may use at the
      bedside to enhance this area of their practice.

PMID- 9604825
TI  - My journey with amyotrophic lateral sclerosis.

PMID- 9604826
TI  - Nuclear cardiology, Part II: Scintigraphic evaluation of cardiac function.
AB  - OBJECTIVE: Different methods are currently available to assess cardiac function,
      especially left ventricular ejection fraction, using either planar or tomographic
      imaging, first-pass or equilibrium techniques, and blood-pool or myocardial
      perfusion agents. This is the second article of a four-part series on nuclear
      cardiology. In this article the authors review the most widely used
      radiopharmaceuticals and methodologies.

PMID- 9604827
TI  - Radiopharmaceuticals for bone malignancy therapy.
AB  - OBJECTIVE: This continuing education article reviews radionuclide bone therapy
      agents that are available commercially and introduces agents that are being
      evaluated for future use. Currently these agents are used to provide pain
      palliation from metastases to bone. Future applications may include adjuvant
      therapy to surgery or external beam treatment. After reading this paper, the
      reader should be able to: (a) describe the desirable characteristics of
      radionuclide bone therapy agents; (b) compare and contrast radiopharmaceuticals
      available for bone therapy; and (c) state the clinical applications of
      radionuclide bone therapy agents.

PMID- 9604828
TI  - Effects of in vitro versus in vivo red cell labeling on image quality in
      gastrointestinal bleeding studies.
AB  - OBJECTIVE: Both in vivo and in vitro red cell labeling methods are available for
      performing gastrointestinal bleeding studies. While in vitro labeling has been
      shown to result in higher binding efficiency, no comparison of clinical image
      quality has been reported between those techniques. This study compares in vivo
      and in vitro methods using both subjective and objective measurements of image
      quality. METHODS: A consecutive series of gastrointestinal bleeding studies
      performed on 23 patients using in vivo labeling was compared to a series of 23
      studies using in vitro labeling. Images at 30 min postinjection were randomized
      and analyzed by two observers. Subjective evaluation of image quality, as well as
      renal activity, was based on a comparison of femoral vein and inferior vena cava
      activity to adjacent background using numerical scores with a scale of 0-3. Image
      quality using the subjective scores was further classified as acceptable and
      poor. Target-to-background measurements of femoral vein to adjacent soft tissue
      in the thigh and inferior vena cava to adjacent abdominal background also were
      made. RESULTS: In vitro label subjective image quality was acceptable in 87% and
      91% of cases for vascular and renal activity, respectively, but only 35% and 52%
      for in vivo labeling. In vitro label target-to-background ratios were
      significantly better than in vivo label for the femoral vein and inferior vena
      cava, as well as for the subjective assessment of vascular image quality, but not
      for renal activity. CONCLUSION: In vitro red cell labeling improves clinical
      image quality as compared with in vivo labeling. Both subjective and objective
      measurements of image quality are useful for comparing the results of labeling
      methods.

PMID- 9604829
TI  - An unusual case of a tibial metastasis as the clinical presentation of
      bronchogenic adenocarcinoma.
AB  - A patient with initial complaints of leg pain and difficulty walking was found to
      have a large right tibial metastatic tumor and poorly differentiated
      adenocarcinoma of the lung. Findings from total-body bone scintigraphy include a
      large area of increased uptake in the proximal half of the right tibia with a
      photon-deficient area medially, and focal areas of uptake in a right rib, in the
      femoral neck and the left ileum. An irregular area of increased uptake in the
      left lung mass was shown by thoracic bone SPECT. This is an unusual case of a
      tibial metastasis as the first clinical presentation of bronchogenic
      adenocarcinoma.

PMID- 9604830
TI  - Dose calibrator assay of iodine-123 and indium-111 with a copper filter.
AB  - OBJECTIVE: The accurate measurement of radionuclides in a dose calibrator can be
      affected by container geometry especially for low-energy photons. This study
      investigated the effectiveness of using copper filtration for selective
      absorption of low-energy x-rays during the measurement of 123I and 111In to
      minimize variations in measurement as a function of geometry. METHODS: Copper
      absorbers of varying thickness were used to define the absorption profile of low
      energy x-rays in the 20- to 50-keV energy window with 125I and a gamma
      scintillation spectrometer. Iodine-123 and 111In standards were assayed in a dose
      calibrator, with and without a copper filter positioned in the ion chamber well,
      to determine new isotope calibration settings for these nuclides with the copper
      filter. Samples of 123I and 111In, of constant activity but various volumes, were
      assayed in 1-ml, 3-ml and 10-ml plastic syringes and a 10-ml glass vial with and
      without copper filtration to assess the influence of geometry on the accuracy of
      measurement. RESULTS: A copper thickness of 0.6 mm removed 99.5% of 125I photons
      in the 20- to 50-keV window and significantly reduced the low-energy component of
      123I and 111In. Activity measurements of 123I and 111In in the dose calibrator
      varied with container type and volume without copper filtration but were
      essentially unchanged when a copper filter was used. CONCLUSION: A copper filter
      > or = 0.6 mm thick eliminates the need for geometry correction factors for
      measuring 123I and 111In with the dose calibrator.

PMID- 9604831
TI  - Suggestion for cause of substandard radiolabeling of red blood cells using
      UltraTag.

PMID- 9604832
TI  - An accurate and inexpensive gamma camera-based system for wipe testing.

PMID- 9604833
TI  - Stopping the smoker's rush.

PMID- 9604835
TI  - The heart of the matter--treating the depressed cardiac patient.

PMID- 9604834
TI  - Improving functioning in patients with Alzheimer's.

PMID- 9604836
TI  - Psychotropic prescription rate rises, despite failure to diagnose.

PMID- 9604837
TI  - Cross-ethnic variations in the care of psychiatric patients: a review of
      contributing factors and practice considerations.
AB  - The number of ethnic minority persons in the United States is increasing faster
      than that of the Caucasian population. This means that nurses will be caring for
      an increasingly diverse patient pool. Ethnic differences have been discovered to
      play a role in the efficacy of psychoactive medication. These differences result
      from a number of biological as well as non biological factors. Nurses have a
      professional obligation to be aware and sensitive to differential response to
      treatment.

PMID- 9604838
TI  - Inpatient group psychotherapy: the role of the staff nurse.
AB  - Inpatient groups are inherently different from outpatient groups and require
      modification in approach. Patients' needs, staff interests and expertise, and the
      needs of the health care system are major driving forces in the development of
      inpatient groups. A co-therapy model helps to achieve a balance between skills
      and abilities of the therapist.

PMID- 9604839
TI  - Assessing mental status in persons with mental retardation.
AB  - When assessing a client, avoid abstract questions, instead ask concrete, open
      ended questions. All clients should be assessed for risk of suicide, elopement,
      or a danger to self or others. Be aware of underlying causes or confounding
      variables that may affect a client's mental status.

PMID- 9604840
TI  - Nursing issues related to post-transplant patients and their families.
AB  - Transplant patients are at risk for developing post-transplant psychiatric
      problems, most commonly delirium, depression, and anxiety. Transplantation
      imposes a significant impact on patients, as well as family members. Therefore,
      the psychological needs of the family unit should be addressed. The advanced
      practice nurse (APN) functioning as a clinician, educator, consultant, or
      researcher has the knowledge and clinical skills to provide continuity of care
      for patients and family members during the transplant process.

PMID- 9604841
TI  - Camp nursing: an opportunity for meeting psychiatric mental health needs.
AB  - The camp nurse used many therapeutic interventions that enhanced growth of
      campers. Having a broad goal to build therapeutic alliances in each interaction
      with others helped the nurse in this experience to accomplish many unforeseen
      positive health outcomes. Each encounter can become an opportunity for growth by
      the participants. Camp nursing is truly an invigorating experience when the nurse
      enters the work place with a positive view that each person displays a variety of
      strengths. Through listening and providing encouragement, the nurse is able to
      assist campers to arrive at answers to difficult issues and leave the experience
      achieving growth and development.

PMID- 9604842
TI  - Reading The Operation: television, realism, and the possession of medical
      knowledge.

PMID- 9604843
TI  - Visual knowledge in medicine and popular film.

PMID- 9604844
TI  - "Fixing" Katie and Eilish: medical documentaries and the subjection of conjoined
      twins.

PMID- 9604845
TI  - From exploitation to self-reflection: representing persons with psychiatric
      disabilities in documentary film.

PMID- 9604846
TI  - Repellent subjects: Hollywood censorship and surgical images in the 1930s.

PMID- 9604847
TI  - The temple of healing: reflections from a physician at the movies.

PMID- 9604848
TI  - Atomic bomb cinema: illness, suffering, and the apocalyptic narrative.

PMID- 9604849
TI  - Ebola goes pop: the filovirus from literature into film.

PMID- 9604850
TI  - Cepharanthine inhibits proliferation of cancer cells by inducing apoptosis.
AB  - Cepharanthine, a biscoclaurine alkaloid extracted from Stephania cepharantha
      Hayata was examined for a possible apoptosis-inducing effect in murine P388
      doxorubicin-sensitive (P388/S) and -resistant (P388/DOX) cells. A significant
      increase in LDH release from cells was observed after P388/S and P388/DOX cells
      had been exposed to cepharanthine for 24 h. Cepharanthine (10 micrograms/ml)
      markedly induced apoptosis in resistant cells after 6 h and 24 h. By the means of
      agarose electrophoresis the DNA ladder was detected in cell lines treated with
      cepharanthine for 24 h. Cepharanthine (1-10 micrograms/ml) also induced the
      production of reactive oxygen species in P388/DOX cells, while no such
      cepharanthine-induced increase in reactive oxygen species was observed in P388/S
      cells. Flow cytometry analysis showed a high level of Fas-antigen expression in
      P388/DOX cells treated with cepharanthine. Furthermore, we found that the
      inhibitition of DNA and protein synthesis caused by cepharanthine (10
      micrograms/ml) was more significant in resistant cells than in sensitive cells.
      Cepharanthine had no effect on the GSH content of P388/S and P388/DOX cells. Our
      experimental results suggest that cepharanthin can induce apoptosis both in
      P388/S and P388/DOX cells, especially in the latter. Apoptosis induced by
      cepharanthine may be implicated in the production of reactive oxygen species and
      Fas-antigen expression in tumor cells.

PMID- 9604851
TI  - Effects of certain resorcinol derivatives on the tyrosinase activity and the
      growth of melanoma cells.
AB  - Effects of certain resorcinol derivatives on tyrosinase activity, melanin
      formation and some other biological activities were studied in order to develop a
      new, potent depigmentor and/or antimelanoma drug. NKO-09, having isopentyl group
      in position 6 of resorcinal, exhibited a more potent effect than the compounds
      which have methyl (NKO-10), ethyl (NKO-11), hexyl (KOM-14), octyl (NKO-14), decyl
      (NKO-19), dodecyl (NKO-15) and tetradecyl (NKO-16) group in inhibiting the
      tyrosinase activities (both tyrosine hydroxylation and dopa oxidation). NKO-09
      was more potent than hydroquinone in inhibiting the tyrosine hydroxylation;
      furthermore, NKO-09 inhibited the dopa oxidation different from hydroquinone. In
      the studies on melanin formation, protein synthesis and the growth of the
      melanoma cells, NKO-09 caused the most potent effect among the test compounds,
      except for the growth of the melanoma cells. KOM-14 was more potent than NKO-09
      in the antimelanoma activity, and its effect was superior than that of 5
      fluorouracil. From these findings, it is suggested that NKO-09 and KOM-14 can be
      used as an efficacious depigmentor and antimelanoma drug, respectively.

PMID- 9604852
TI  - Paclitaxel, bropirimine and linomide: effect on growth inhibition in a murine
      prostate cancer model by different growth regulatory mechanisms.
AB  - Paclitaxel, bropirimine and linomide therapy was evaluated in a murine prostate
      cancer model. All drugs were effective in impeding tumor growth but the
      mechanisms of action varied. Paclitaxel inhibited bcl-2 expression suggesting an
      apoptotic mechanism. Bropirimine, while inhibiting bcl-2 expression also
      significantly depressed tumor necrosis factor-alpha (TNF-alpha) expression. In
      the bropirimine treated group there was also a correlation between angiogenesis
      and cyclin D expression. Finally, linomide significantly decreased angiogenesis.
      Since the mechanism of action of these drugs differ, combining them at lower
      doses might maintain therapeutic efficacy while reducing toxicity.

PMID- 9604853
TI  - The natriuretic activity of the K+ channel blocker U-37883A displays an ADH
      dependence.
AB  - We reported previously that K+ channel blockers induce diuresis and natriuresis
      in conscious and anesthetized rats. Free-water clearance studies suggested that
      K+ channel blockers inhibit NaCl reabsorption in the thick ascending limb (TAL)
      by blocking K+ recycling through a low-conductance, usually open, apical ATP
      sensitive K+ channel. In the present study, we measured the effect of U-37883A
      (15 mg/kg, i.v.) on Na+ reabsorption in rats preconditioned to alter ADH levels.
      In water-loaded animals with suppressed ADH levels, U-37883A was 50% less
      natriuretic than in saline-loaded rats. Infusion of ADH to water-loaded rats
      restored the natriuretic response to a level comparable to saline-loaded rats.
      Loss of natriuretic efficacy was not secondary to changes in GFR or renal
      perfusion pressure since GFRs did not vary before or after drug administration in
      any of the respective groups. Decreases in blood pressure were not significantly
      different in saline-loaded, water-loaded and water-loaded/ADH rats. The
      natriuretic response of U-37883A as varied by ADH levels may be the first
      observation, in vivo, to support the observation that the cotransporter in TAL
      can exist in two modes as previously observed in vitro by Hebert and colleagues.

PMID- 9604854
TI  - Inhibition of glycine-induced current by morphine in nucleus tractus solitarii
      neurones of guinea pigs.
AB  - We studied the effect of morphine on the current induced by glycine in acutely
      dissociated nucleus tractus solitarii (NTS) neurones of guinea pigs, by use of
      the whole-cell patch clamp technique. Morphine inhibited 30 microM glycine
      induced current (Igly), without affecting the current caused by 30 microM GABA.
      The effect of morphine was concentration-dependent, with a maximal effect at 1
      mM, and reversible. The half-maximum inhibitory concentration of morphine was 30
      microM. The effect of morphine was not depressed by naloxone, an opioid
      antagonist. Furthermore, the effect was not substantially affected by
      methiothepin, a 5-HT1 antagonist, ketanserin, a 5-HT2 antagonist and MDL-72222, a
      5-HT3 antagonist. Morphine at 30 microM shifted the concentration-response curve
      for Igly to the right without affecting the maximum value. The effect of morphine
      on Igly showed no use-dependence. The results indicate that morphine inhibits
      Igly in the NTS neurones, and further suggest that morphine at the concentration
      used may act on the glycine receptor-ionophore complex, but not on the Cl-channel
      of the complex.

PMID- 9604856
TI  - Pharmacodynamic methods for investigating antiasthma drugs in healthy volunteers.
AB  - The investigation of bronchoactive drugs in healthy volunteers may be divided
      into studies on the drug effects on basal airway calibre, the effects on induced
      bronchoconstriction and the examination of the pharmacokinetic and side effect
      profile of new chemical entities. In the studies presented in this paper, whole
      body plethysmography was used to assess the pharmacological activity of three new
      development compounds. In the first example, bronchodilatation was measured after
      administration of an anticholinergic drug. In two further examples, the bronchial
      effects were studied in asthma models in which an increase in airflow resistance
      was produced using inhaled methacholine and platelet activating factor (PAF). The
      method applied in these tests allowed the antagonistic effects of drugs on the
      constrictor effect of individual agents to be followed. Antiasthmatic drugs can
      also have a systemic effect on different physiological and biochemical
      parameters. These parameters can be applied as useful tools in the determination
      of the pharmacological activity of a given drug, irrespective of the conventional
      methods used to evaluate the efficacy of bronchodilators by the degree of
      bronchial muscular relaxation. A complex nonbronchial model is shown in order to
      demonstrate how it is possible to identify the pharmacologically effective dose
      of a new beta 2-adrenoceptor agonist.

PMID- 9604855
TI  - Urinary excretion of acetazolamide in healthy volunteers after short- and long
      term exposure to high altitude.
AB  - Acetazolamide is recommended for the prophylaxis of acute mountain sickness
      symptoms which sets in on climbing to high altitudes (H) above 2,500 m. It is
      primarily excreted unchanged in urine. In a previous study, we reported on the
      changes in urinary excretion of meperidine and its metabolite normeperidine on
      exposure to high altitude. In this study, we investigated the effect on urinary
      excretion of acetazolamide. The study was carried out in three groups of 12
      healthy male volunteers each: at sea level (group L), these same volunteers the
      day after arrival at high altitude of 4,360 m (group HA), and subjects residing
      for approximately 10 months at high altitude (group HC). Urine was collected for
      the periods of 0-2, 2-4, 4-8, 8-12, 12-24 and 24-36 h after peroral
      administration of a single 250 mg dose. Urinary pH was measured and the
      concentrations of acetazolamide were determined. There were no significant
      changes observed in the amount of acetazolamide excreted in urine over 36 h. The
      urinary pH ranged from 4.5 to 7.8 for L, from 4.2 to 6.9 for HA and from 3.1 to
      6.7 for HC. The Fel (fraction eliminated unchanged in urine) was calculated from
      the amount excreted in 36 h in urine and dose, assuming a bioavailability of 1
      based on literature data. No significant changes in Fel were seen.

PMID- 9604857
TI  - Delayed auditory feedback during smoking cessation.
AB  - Delays between speech production and hearing, delayed auditory feedback (DAF),
      reduce speech and reading rates. Smoking cessation in heavy smokers causes
      subjective reports of difficulty in concentration, decrements in cognitive
      performance, and EEG changes. The purpose of the present study was to determine
      if tobacco cessation disrupts linguistic processing as modeled by the DAF
      paradigm. Smokers (n = 14) were tested on 3 d of ad libitum smoking and 3 d no
      smoking. At each session, they read a word list (24 words) and a story (about 57
      words) with and without delay (220 msec). The delay significantly decreased
      reading speed of the story from 3.4 to 2.9 words per second (wps) and of list
      from 2.1 to 1.7 wps. However, tobacco cessation had no significant effect on
      reading speed and no interaction with DAF. Although tobacco withdrawal slows
      performance on cognitive tasks, linguistic processing modeled by DAF is
      preserved. DAF may prove useful for the study of other drug classes and drug
      withdrawal states.

PMID- 9604858
TI  - Effect of differently processed coffee on the gastric potential difference and
      intragastric pH in healthy volunteers.
AB  - The gastric irritation potential of orally administered coffee (150 ml) was
      investigated in four healthy volunteers by continuous measurement of gastric
      potential difference (GPD) and intragastric pH. Furthermore, serum gastrin
      concentrations were measured up to 45 min after administration of the coffee. One
      of the coffees, untreated, had to be compared with a pretreated coffee. The
      evaluation of the target parameters Reiz-Index, AUB, Pdmax and ttot revealed a
      significant difference between untreated coffee and specially treated coffee: the
      improved coffee processing produced significantly less mucosal irritation.
      Regarding the intragastric pH, no significant differences between the treatments
      were observed and no stimulation of gastric acid secretion following coffee was
      measurable. No consistent effect on serum gastrin concentration was seen: two of
      the four subjects had a steep increase in serum gastrin following administration
      with a clear difference between the differently processed coffees, whereas the
      other two subjects showed no change in serum gastrin. The results of this pilot
      study confirm the findings of former experiments on the reliability of continuous
      transmural GPD measurement when investigating the mucosal irritation potential of
      barrier breakers.

PMID- 9604859
TI  - Losartan in Cushing's syndrome.
AB  - Eleven patients with Cushing's syndrome were included in the study. They
      maintained their usual sodium intake and received a single oral dose of 50 mg of
      the angiotensin II antagonist receptor losartan for 3 days. Losartan treatment
      resulted in stimulation of active renin and decrease of plasma and urinary
      kallikrein activity. Both systolic and diastolic blood pressure decreased
      independently of baseline level of active renin. The relationship between
      kallikrein and renin-angiotensin system are discussed.

PMID- 9604860
TI  - Protein kinase C activation and the development of diabetic complications.
AB  - Recent studies have identified that the activation of protein kinase C (PKC) and
      increased diacylglycerol (DAG) levels initiated by hyperglycemia are associated
      with many vascular abnormalities in retinal, renal, and cardiovascular tissues.
      Among the various PKC isoforms, the beta- and delta-isoforms appear to be
      activated preferentially in the vasculatures of diabetic animals, although other
      PKC isoforms are also increased in the renal glomeruli and retina. The glucose
      induced activation of PKC has been shown to increase the production of
      extracellular matrix and cytokines; to enhance contractility, permeability, and
      vascular cell proliferation; to induce the activation of cytosolic phospholipase
      A2; and to inhibit Na+-K+-ATPase. The synthesis and characterization of a
      specific inhibitor for PKC-beta isoforms have confirmed the role of PKC
      activation in mediating hyperglycemic effects on vascular cells, as described
      above, and provide in vivo evidence that PKC activation could be responsible for
      abnormal retinal and renal hemodynamics in diabetic animals. Transgenic mice
      overexpressing PKC-beta isoform in the myocardium developed cardiac hypertrophy
      and failure, further supporting the hypothesis that PKC-beta isoform activation
      can cause vascular dysfunctions. Interestingly, hyperglycemia-induced oxidative
      stress may also mediate the adverse effects of PKC-beta isoforms by the
      activation of the DAG-PKC pathway, since treatment with D-alpha-tocopherol was
      able to prevent many glucose-induced vascular dysfunctions and inhibit DAG-PKC
      activation. Clinical studies are now in progress to determine whether PKC-beta
      inhibition can prevent diabetic complications.

PMID- 9604861
TI  - Small amounts of fructose markedly augment net hepatic glucose uptake in the
      conscious dog.
AB  - Fructose activates glucokinase by releasing the enzyme from its inhibitory
      protein in liver. To examine the importance of acute activation of glucokinase in
      regulating hepatic glucose uptake, the effect of intraportal infusion of a small
      amount of fructose on net hepatic glucose uptake (NHGU) was examined in 42 h
      fasted conscious dogs. Isotopic ([3-3H] and [U-14C]glucose) and arteriovenous
      difference methods were used. Each study consisted of an equilibration period (
      90 to -30 min), a control period (-30 to 0 min), and a
      hyperglycemic/hyperinsulinemic period (0-390 min). During the latter period,
      somatostatin (489 pmol x kg(-1) x min(-1)) was given, along with intraportal
      insulin (7.2 pmol x kg(-1) x min(-1)) and glucagon (0.5 ng x kg(-1) x min(-1)).
      In this way, the liver sinusoidal insulin level was fixed at four times basal
      (456 +/- 60 pmol/l), and liver sinusoidal glucagon level was kept basal (46 +/- 6
      ng/l). Glucose was infused through a peripheral vein to create hyperglycemia
      (12.5 mmol/l plasma). Hyperglycemic hyperinsulinemia (no fructose) switched net
      hepatic glucose balance (micromoles per kilogram per minute) from output (11.3 +/
      1.4) to uptake (14.7 +/- 1.7) and net lactate balance (micromoles per kilogram
      per minute) from uptake (6.5 +/- 2.1) to output (4.4 +/- 1.5). Fructose was
      infused intraportally at a rate of 1.7, 3.3, or 6.7 micromol x kg(-1) x min(-1),
      starting at 120, 210, or 300 min, respectively. In the three periods, portal
      blood fructose increased from <6 to 113 +/- 14, 209 +/- 29, and 426 +/- 62
      micromol/l, and net hepatic fructose uptake increased from 0.03 +/- 0.01 to 1.3
      +/- 0.4, 2.3 +/- 0.7, and 5.1 +/- 0.6 micromol x kg(-1) x min(-1), respectively.
      NHGU increased to 41 +/- 3, 54 +/- 5, and 69 +/- 8 micromol x kg(-1) x min(-1),
      respectively, and net hepatic lactate output increased to 11.0 +/- 3.2, 15.3 +/-
      2.7, and 22.4 +/- 2.8 micromol x kg(-1) x min(-1) in the three fructose periods,
      respectively. The amount of [3H]glucose incorporated into glycogen was equivalent
      to 69 +/- 3% of [3H]glucose taken up by the liver. These data suggest that
      glucokinase translocation within the hepatocyte is a major determinant of hepatic
      glucose uptake by the dog in vivo.

PMID- 9604862
TI  - Glucose-6-phosphate and Ca2+ sequestration are mutually enhanced in microsomes
      from liver, brain, and heart.
AB  - Microsomes prepared from three rat tissues were examined for their ability to
      import glucose-6-phosphate (G-6-P). Microsomes from liver, which possess a high
      level of glucose-6-phosphatase activity, were compared with those from cerebral
      cortex and cardiac muscle, which are not involved in the export of glucose and in
      which glucose-6-phosphatase activity is relatively low. In all three, a selective
      permeability to G-6-P was detected by light scattering. However, the sugar
      phosphate specificity of the transport process differed. G-6-P was able to
      enhance ATP-dependent Ca2+ sequestration in all three types of microsomes. In
      addition, enzymatic detection of G-6-P after the rapid filtration of microsomes
      determined that, in the absence of Ca2+ and ATP, a level of intramicrosomal G-6-P
      approaching a passive equilibrium with the extramicrosomal G-6-P concentration
      was rapidly achieved in all three tissues. However, under conditions in which
      Ca2+ was being actively accumulated, the intramicrosomal levels of G-6-P exceeded
      the equilibrium value by three- to fourfold. This enhanced sequestration was not
      observed in the presence of Ca2+ or ATP alone or in the presence of a Ca2+
      ionophore or an inhibitor of the microsomal Ca2+ ATPase. These data are
      consistent with a selective import pathway into the endoplasmic/sarcoplasmic
      reticulum for G-6-P independent of glucose-6-phosphatase activity. In addition,
      they suggest an alternate explanation for the enhanced sequestration of Ca2+ by
      the endoplasmic/sarcoplasmic reticulum of intact cells seen when extracellular
      glucose is increased.

PMID- 9604863
TI  - Development and regulation of glucose-6-phosphatase gene expression in rat liver,
      intestine, and kidney: in vivo and in vitro studies in cultured fetal
      hepatocytes.
AB  - The mRNA and the activity of glucose-6-phosphatase (Glc-6-Pase) were present in
      the liver, kidney, and small intestine of 15-day-old suckling rats, but were
      absent from the stomach, colon, lung, white and brown adipose tissues, muscle,
      heart, brain, and spleen. The mRNA encoding Glc-6-Pase was present in the liver
      of 21-day-old fetal rats and increased markedly immediately after birth. From 5
      days after birth to the end of the suckling period, it returned to 50% of the
      level found in the liver of 48-h starved adult rats. When rats were weaned at 21
      days onto a high-carbohydrate, low-fat (HCLF) diet, the concentration of liver
      Glc-6-Pase mRNA was markedly increased. In the fetal rat jejunum, the activity
      and mRNA of Glc-6-Pase were very low. It increased during the 5 days after birth
      and then declined to reach very low levels. Neither mRNA nor activity of Glc-6
      Pase was present in the fetal kidney. They appeared and increased slowly during
      the suckling period to reach maximal levels 15 days after birth and then remained
      constant. Weaning onto the HCLF diet did not change the Glc-6-Pase gene
      expression, neither in the jejunum nor in the kidney. The regulation of Glc-6
      Pase gene expression by hormones and nutrients was studied in cultured
      hepatocytes from 20-day-old rat fetuses. Bt2cAMP stimulated the Glc-6-Pase gene
      expression in a dose-dependent manner. This probably resulted from an increased
      gene transcription since the half-life of the transcript was not affected by
      dibutyryl cAMP (Bt2cAMP). The Bt2cAMP-induced Glc-6-Pase mRNA accumulation was
      antagonized by insulin in a dose-dependent manner. Long-chain fatty acids
      (LCFAs), but not medium-chain fatty acids, induced the accumulation of Glc-6-Pase
      mRNA and the stabilization of the transcript. The peroxisome proliferator,
      clofibrate, induced a threefold increase in Glc-6-Pase mRNA concentration. Both
      stimulation of Glc-6-Pase mRNA by LCFAs and clofibrate were inhibited by insulin.
      Increasing concentrations of glucose (from 0 to 20 mmol/l) did not affect the
      Bt2cAMP-induced Glc-6-Pase gene expression. By contrast, high glucose
      concentration (25 mmol/l) markedly induced the Glc-6-Pase gene expression in fed
      adult rat hepatocytes. The difference in the response to glucose between fetal
      and adult rat hepatocytes is discussed. We conclude that the rapid increase in
      hepatic Glc-6-Pase mRNA levels that accompanies the fetal-to-neonatal transition
      in the rat is triggered by the reciprocal change in circulating insulin and LCFA
      concentrations, coupled to the rise in liver cAMP concentration.

PMID- 9604864
TI  - Hypothalamic corticotropin-releasing hormone is a mediator of the anorexigenic
      effect of leptin.
AB  - Leptin, ob gene product, inhibits feeding behavior and stimulates energy
      expenditure in rodents. Corticotropin-releasing hormone (CRH) and neuropeptide Y
      (NPY), which act in the hypothalamus to influence energy homeostasis, may mediate
      the anorexic effect of leptin. The present studies were undertaken to examine the
      possible involvement of hypothalamic CRH in the anorexigenic action of leptin in
      male Wistar rats. Recombinant leptin (2 microg/rat), microinjected into the third
      ventricle, inhibited food intake at 2 h by 33.3% (P < 0.01) in rats that were
      deprived of food for 18 h. The intracerebroventricular injection of 2 microg
      leptin also increased hypothalamic CRH content (P < 0.05) at 2 h after its
      administration. Simultaneous intracerebroventricular administration of 5
      microg/rat alpha-helical CRH 9-41 (alpha-hCRH), a CRH antagonist, with 2
      microg/rat leptin attenuated the anorexic effect of leptin by 2 h. In contrast,
      single intracerebroventricular injection of alpha-hCRH did not affect food
      consumption in food-deprived rats. These results implicate hypothalamic CRH as an
      important mediator of the anorexic effect of leptin in food-deprived rats.

PMID- 9604865
TI  - Induction of GAD65-specific regulatory T-cells inhibits ongoing autoimmune
      diabetes in nonobese diabetic mice.
AB  - IDDM is a T-cell-mediated autoimmune disease in which the insulin-producing beta
      cells are destroyed. The disease process is complex, involving the recognition of
      several beta-cell autoantigens. One of these, GAD65, appears to have a critical
      and not fully defined role in IDDM in humans and in the NOD mouse. We provide
      evidence that an ongoing diabetogenic response in NOD mice can be suppressed
      after intravenous administration of GAD65, but not by other beta-cell
      autoantigens. Furthermore, suppression of the diabetogenic response is mediated
      by the induction of GAD65-specific CD4+ regulatory T-cells. Finally, cytokine
      analysis indicates that these CD4+ regulatory T-cells have a T-helper 2
      phenotype.

PMID- 9604866
TI  - Reconstitution of glucotoxic HIT-T15 cells with somatostatin transcription factor
      1 partially restores insulin promoter activity.
AB  - We have reported that chronic culture of HIT-T15 cells in medium containing
      supraphysiologic glucose concentrations (11.1 mmol/l) causes a decrease in
      insulin mRNA levels, insulin content, and insulin release. Furthermore, decreases
      in insulin gene transcription and binding activity of two essential beta-cell
      transcription factors, somatostatin transcription factor-1 (STF-1; also known as
      GSTF, IDX-1, IPF-1, PDX-1, and GSF) and RIPE-3b1 activator, are associated with
      this glucotoxic effect. In this study, we observed that the loss of RIPE-3b1
      occurs much earlier (79% decrease at passage [p]81) than the loss of STF-1 (65%
      decrease at p104), with abolishment of both factors by p122. Since the STF-1, but
      not the RIPE-3b1 activator, gene has been cloned, we examined its restorative
      effects on insulin gene promoter activity after reconstitution with STF-1 cDNA.
      Basal insulin promoter activities normalized to early (p71-74) passage cells
      (1.000 +/- 0.069) were 0.4066 +/- 0.093 and 0.142 +/- 0.034 for intermediate
      (p102-106) and late (p118-122) passage cells, respectively. Early, intermediate,
      and late passage cells, all chronically cultured in medium containing 11.1 mmol/l
      glucose, were transfected with STF-1 alone or cotransfected with E2-5, an E-box
      factor known to be synergistically associated with STF-1. Compared with basal
      levels, we observed a trend toward an increase in insulin promoter activity in
      intermediate passage cells with STF-1 transfection (1.43-fold) that became a
      significant increase when E2-5 was cotransfected (1.78-fold). In late passage
      cells, transfection of STF-1 alone significantly stimulated a 2.2-fold increase
      in the insulin promoter activity. Cotransfection of STF-1 and E2-5 in late
      passage cells stimulated insulin promoter activity 2.8-fold, which was 40% of the
      activity observed in early passage cells. Control studies in glucotoxic betaTC-6
      cells deficient in RIPE-3b1 activator but not STF-1 did not demonstrate an
      increase in insulin promoter activity after STF-1 transfection. We conclude that
      loss of RIPE-3b1 activity precedes loss of STF-1 activity in glucotoxic HIT-T15
      cells and that defective promoter activity can be partially restored by STF-1
      transfection and predict that eventual cloning of the RIPE-3b1 gene will allow
      cotransfection studies with both factors that will allow full reconstitution of
      insulin promoter activity.

PMID- 9604867
TI  - Atypical protein kinase C isozyme zeta mediates carbachol-stimulated insulin
      secretion in RINm5F cells.
AB  - Carbachol-stimulated insulin release in the RINm5F cell is associated with
      elevation of the cytosolic Ca2+ concentration ([Ca2+]i) through mobilization of
      Ca2+ from thapsigargin-sensitive intracellular stores and with the generation of
      diacylglycerol (DAG). Thus carbachol activates phospholipase C, and this was
      thought to be the means by which it stimulates insulin secretion. However, when
      the elevation of [Ca2+]i was blocked by thapsigargin, the effect of carbachol to
      stimulate insulin release was unchanged. Thus the effect of carbachol to increase
      [Ca2+]i was dissociated from the stimulation of release. When the role of protein
      kinase C (PKC) was examined, carbachol-stimulated insulin release was found to be
      unaffected by phorbol ester-induced downregulation of PKC, using 12-O
      tetradecanoylphorbol-13-acetate (TPA), and by the PKC inhibitors staurosporine,
      bisindolylmaleimide, and 1-O-hexadecyl-2-O-methylglycerol (AMG-C16). These
      treatments abolished the stimulation of release by TPA. Thus the carbachol
      activation of PKC appeared also to be dissociated from the stimulation of insulin
      release. However, when the activation of several different PKC isozymes was
      studied, an atypical PKC isozyme, zeta, was found to be translocated by
      carbachol. By Western blotting analysis, carbachol selectively translocated the
      conventional PKC isozymes alpha and beta (the activation of which is dependent on
      Ca2+ and DAG) from the cytosol to the membrane. Carbachol also translocated the
      atypical PKC isozyme zeta, which is insensitive to Ca2+, DAG, and phorbol esters.
      The PKC inhibitors staurosporine, bisindolylmaleimide, and AMG-C16 blocked the
      stimulated translocation of PKC-alpha and -beta, but not that of PKC-zeta.
      Prolonged treatment of the cells with TPA downregulated PKC-alpha and -beta, but
      not PKC-zeta. Under all these conditions, carbachol-stimulated insulin release
      was unaffected. However, a pseudosubstrate peptide inhibitor specific for PKC
      zeta inhibited the translocation of PKC-zeta and 70% of the carbachol-stimulated
      insulin secretion. The data indicate that carbachol-stimulated insulin release in
      RINm5F cells is mediated to a large degree by the activation of the atypical PKC
      isozyme zeta.

PMID- 9604868
TI  - Leptin secretion from subcutaneous and visceral adipose tissue in women.
AB  - Upper body obesity is a risk factor for type 2 diabetes. Little is known about
      the regulation of body fat distribution, but leptin may be involved. This study
      examined the secretion of leptin in subcutaneous and omental fat tissue in 15
      obese and 8 nonobese women. Leptin secretion rates were two to three times higher
      in subcutaneous than in omental fat tissue in both obese and nonobese women (P <
      0.0001 and P < 0.001, respectively). There was a positive correlation between BMI
      and leptin secretion rates in both subcutaneous (r = 0.87, P < 0.0001) and
      omental (r = 0.74, P < 0.0001) fat tissue. Furthermore, leptin secretion rates in
      subcutaneous and omental fat tissue correlated well with serum leptin levels (r =
      0.84, P < 0.0001 and r = 0.73, P = 0.001, respectively), although in multivariate
      analysis, the subcutaneous leptin secretion rate was the major regressor for
      serum leptin (F = 42). Subcutaneous fat cells were approximately 50% larger than
      omental fat cells, and there was a positive correlation between fat cell size and
      leptin secretion rate in both fat depots (r = 0.8, P < 0.01). Leptin (but not
      gamma-actin) mRNA levels were twofold higher in subcutaneous than in omental fat
      tissue (P < 0.05). Thus the subcutaneous fat depot is the major source of leptin
      in women owing to the combination of a mass effect (subcutaneous fat being the
      major depot) and a higher secretion rate in the subcutaneous than in the visceral
      region, which in turn could be due to increased cell size and leptin gene
      expression.

PMID- 9604869
TI  - Arteriolar reactivity in conscious diabetic rats: influence of aminoguanidine
      treatment.
AB  - The effect of 6 weeks' streptozotocin (STZ)-induced (70 mg/kg) diabetes and
      aminoguanidine (AG) treatment (50 mg/kg s.c. or 250-750 mg/l given in drinking
      water) on arteriolar reactivity to vasoactive substances was investigated in
      conscious rats. Studies were performed in untreated control rats (n = 13), STZ
      induced diabetic rats (n = 11), AG-treated control rats (n = 12), and AG-treated
      diabetic rats (n = 12). Rats were provided with a dorsal microcirculatory chamber
      that allowed intravital microscopy of striated muscle arterioles of varying
      diameter (A1, large; A2, intermediate; and A3, small arterioles) in conscious
      animals. The mean arterial pressure (MAP) and arteriolar diameter responses to
      intravenous infusion of the following drugs were examined: the endothelium
      dependent vasodilator acetylcholine (ACh; 3, 10, and 30 microg x kg(-1) x min(
      1)), the potassium-channel opener levcromakalim (LC; 30 microg/kg), and the
      vasoconstrictor agents ANG II (0.1 and 0.3 microg x kg(-1) x min(-1)) and
      norepinephrine (NE; 0.2, 0.6, and 2.0 microg x kg(-1) x min(-1)). Baseline MAP
      was lower in both diabetic groups versus the nondiabetic groups (P < 0.05). AG
      treatment had no influence on baseline MAP. The absolute change in MAP after drug
      infusion tended to be lower in the diabetic rats than in their nondiabetic
      littermates. Arteriolar vasodilatory responses to ACh and LC were attenuated in
      the diabetic animals (1 +/- 7 vs. 19 +/- 7% [P < 0.05] and 7 +/- 3 vs. 34 +/- 8%
      [P < 0.01] in A2, respectively). AG treatment of diabetic animals did not prevent
      the development of this disturbance. Vasoconstrictor responses were not
      influenced by the diabetic state. In the intermediate arterioles of AG-treated
      control rats, a hyperresponse was observed after ANG II infusion (-10 +/- 2 vs. 
      2 +/- 2%; P < 0.05) and a hyporesponse was observed after ACh and LC infusion (2
      +/- 3 and 15 +/- 6%, respectively; P < 0.05 vs. untreated control rats). These
      data indicate that 6 weeks of experimental diabetes is associated with a
      decreased endothelium-dependent and -independent vasodilatation. AG treatment had
      no beneficial effect on this disturbance.

PMID- 9604870
TI  - Octreotide prevents the early increase in renal insulin-like growth factor
      binding protein 1 in streptozotocin diabetic rats.
AB  - The early renal growth in streptozotocin (STZ)-induced diabetic rats is preceded
      by a transient rise in renal tissue insulin-like growth factor (IGF)-I
      concentration. Administration of the long-acting somatostatin analog octreotide
      to STZ diabetic rats inhibits the early increase in kidney IGF-I and the increase
      in kidney size without affecting metabolic control. We studied the effects of
      octreotide treatment on the intrarenal IGF axis at 2 and at 7 days after the
      induction of STZ diabetes. Two days after induction of diabetes, kidney IGF-I was
      increased from 850 +/- 43 ng/g tissue in controls to 1,648 +/- 165 ng/g tissue (P
      < 0.001) in diabetic animals. The diabetes-associated increase in renal IGF-I 48
      h after STZ injection was totally prevented by octreotide (IGF = 780 +/- 57 ng/g
      tissue). However, 7 days after the induction of diabetes, kidney IGF-I was
      similar to that of control and was not affected by octreotide. No difference in
      serum IGF-I was observed between controls and diabetic rats after 2 days of
      diabetes; however, octreotide treatment resulted in a significant decrease of
      serum IGF-I after 2 days when compared with control rats (P < 0.05). Renal IGF-I
      mRNA was significantly decreased to the same extent in both diabetic groups 2 and
      7 days after the induction of diabetes, while renal IGF-I receptor (IGF-IR) mRNA
      was unchanged in rats from either group. Two days after induction of diabetes,
      renal insulin-like growth factor binding protein (IGFBP)-1 mRNA and 30-kDa IGFBPs
      (containing IGFBP-1) increased by 186 and 192%, respectively, in untreated
      diabetic animals compared with controls. Octreotide treatment prevented the
      diabetes-associated rise in renal IGFBP-1 mRNA and protein. However, 7 days after
      the induction of diabetes, renal IGFBP-1 mRNA and protein were similarly
      increased in both octreotide-treated or untreated diabetic rats. Renal IGFBP-3
      gene expression and protein and IGFPB-5 mRNA remained unchanged after 2 and 7
      days of diabetes when treated or untreated with octreotide. We conclude that the
      well-known inhibitory effect of octreotide on the early increase in renal IGF-I
      concentration and renal size in diabetes may be mediated through a direct effect
      on renal IGFBP-1 levels.

PMID- 9604871
TI  - High glucose induces alteration of gap junction permeability and phosphorylation
      of connexin-43 in cultured aortic smooth muscle cells.
AB  - Gap junction is thought to have a crucial role in maintaining tissue homeostasis.
      We examined the effect of a high glucose level on gap junctional intercellular
      communication (GJIC) activity in cultured vascular smooth muscle cells (VSMCs)
      using the fluorescent dye transfer method. After a 48-h incubation with 22 mmol/l
      glucose (high glucose level), GJIC activity of VSMCs was significantly reduced
      compared with incubation with 5.5 mmol/l glucose (normal glucose level) (P <
      0.05). Treatment of the cells with 12-O-tetradecanoylphorbol-13-acetate (TPA; 5 x
      10(-8) mol/l), a protein kinase C (PKC) activator, for 1 h also reduced GJIC
      activity (P < 0.01). In addition, treatment of the cells with calphostin C, a
      specific PKC inhibitor, for 3 h completely restored the GJIC activity inhibited
      by the high glucose level. Western blot analysis showed that connexin 43 (Cx43),
      which is the major functional protein of gap junction, is present in
      multiphosphorylated forms: a nonphosphorylated form (P0) and phosphorylated forms
      (P1, P2, and P3). Incubation of VSMCs with a high glucose level significantly
      increased the density ratio of P3/P0 compared with a normal glucose level (P <
      0.05). Similarly, treatment of the cells with TPA significantly increased the
      P3/P0 ratio compared with controls (P < 0.01). In addition, the increase in the
      P3/P0 density ratio induced by a high glucose level was restored to the control
      level by both staurosporine and calphostin C. These results suggest that the high
      glucose level induced the inhibition of GJIC activity in cultured VSMCs through
      excessive phosphorylation of Cx43, mediated by PKC activation. This may
      contribute to the development of the macroangiopathy associated with diabetes.

PMID- 9604872
TI  - Insulin increases endothelin-1-evoked intracellular free calcium responses by
      increased ET(A) receptor expression in rat aortic smooth muscle cells.
AB  - While insulin is known to promote vascular smooth muscle (VSM) relaxation, it
      also enhances endothelin-1 (ET-1) secretion and action in conditions such as
      NIDDM and hypertension. We examined the effect of insulin pretreatment on
      intracellular free calcium ([Ca2+]i) responses to ET-1 in cultured aortic smooth
      muscle cells (ASMCs) isolated from Sprague-Dawley (SD) rats and measured ET(A)
      receptor characteristics and ET-1-evoked tension responses in aorta obtained from
      insulin-resistant, hyperinsulinemic Zucker-obese (ZO) and control Zucker-lean
      (ZL) rats. Pretreatment of rat ASMCs with insulin (10 nmol/l for 24 h) failed to
      affect basal [Ca2+]i levels but led to a significant increase in peak [Ca2+]i
      response (1.7-fold; P < 0.01) to ET-1. The responses to IRL-1620 (an ET(B)
      selective agonist), ANG II, and vasopressin remained unaffected. ET-1-evoked peak
      [Ca2+]i responses were significantly attenuated by the inclusion of the ET(A)
      antagonist, BQ123, in both groups. The ET(B) antagonist, BQ788, abolished [Ca2+]i
      responses to IRL-1620 but failed to affect the exaggerated [Ca2+]i responses to
      ET-1. Saturation binding studies revealed a twofold increase (P < 0.01) in
      maximal number of binding sites labeled by 125I-labeled ET-1 in insulin
      pretreated cells and no significant differences in sites labeled by 125I-labeled
      IRL-1620 between control and treatment groups. Northern blot analysis revealed an
      increase in ET(A) mRNA levels after insulin pretreatment for 20 h, an effect that
      was blocked by genistein, actinomycin D, and cycloheximide. Maximal tension
      development to ET-1 was significantly greater (P < 0.01), and microsomal binding
      studies using [3H]BQ-123 revealed a twofold higher number of ET(A) specific
      binding sites (P < 0.01) in aorta from ZO rats compared with that of ZL rats.
      These data suggest that insulin exaggerates ET-1-evoked peak [Ca2+]i responses
      via increased vascular ET(A) receptor expression, which may contribute to
      enhanced vasoconstriction observed in hyperinsulinemic states.

PMID- 9604873
TI  - Constitutive nitric oxide synthase expression in retinal vascular endothelial
      cells is suppressed by high glucose and advanced glycation end products.
AB  - It has been suggested that increased production of nitric oxide (NO), a potent
      endothelium-derived vasodilator, may be responsible for increased blood flow in
      the retinal and renal vascular beds in early diabetes. However, NO-mediated
      vasodilation has been reported as impaired in diabetes, and there is evidence
      that the synthesis and release of NO by the vascular endothelium may be flawed in
      this condition. We examined the effect of high ambient glucose and exposure to
      exogenous glycated proteins on NO synthesis in cultured retinal microvascular
      endothelial cells (RMECs), using a polarographic sensor to measure released NO
      gas. Nitrite (the stable end product of the reaction between NO and molecular
      oxygen) was measured in tissue culture supernatants. The expression of vascular
      endothelial constitutive nitric oxide synthase (eNOS), which is responsible for
      NO synthesis in endothelial cells, was studied by Western blot analysis and
      Northern hybridization experiments. A dose-dependent reduction of NO synthesis by
      RMECs occurred 5 days after exposure to 15 and 25 mmol/l glucose, and
      concomitantly we found that accumulation of nitrite in culture supernatants of
      high-glucose exposed cells was also reduced. Coincubation of endothelial cells
      with inhibitors of protein kinase C (PKC) increased the accumulation of nitrite
      but did not restore it to the levels obtained when cells were cultured in 5
      mmol/l glucose. The expression of eNOS by RMECs was markedly reduced by 5 days of
      exposure to 25 mmol/l glucose and glycated albumin. This study implicates the PKC
      pathway, which is known to be upregulated on exposure to high ambient glucose
      concentrations, as a possible factor in the inhibition of eNOS expression in
      RMECs. This study also suggests that glycated proteins may be involved in the
      pathogenesis of vascular endothelial dysfunction by modulating the nitric oxide
      synthase (NOS)/NO pathway in retinal vascular endothelial cells.

PMID- 9604874
TI  - Postprandial triglyceride response in visceral obesity in men.
AB  - Although metabolic disturbances are often observed in obese patients, increased
      accumulation of visceral adipose tissue (AT) has been shown to be more closely
      associated with high fasting triglyceride (TG) and insulin levels as well as with
      low HDL cholesterol concentrations than with excess body fatness per se.
      Interestingly, the fasting concentration of plasma TGs has been shown to be an
      important determinant of the magnitude and duration of the postprandial TG
      response. Yet little is known about the respective contributions of obesity
      versus excess visceral AT to the variation in postprandial TG clearance. In the
      present study, we examined potential differences in postprandial triglyceride
      rich lipoprotein (TRL) responses in subjects characterized by high versus low
      levels of visceral AT. In a sample of 43 men (mean age: 41.3 +/- 9.6 years), we
      found that both excess body fat and visceral obesity were associated with
      increased postprandial TG responses in total TRL (r = 0.33-0.45). We also found a
      strong relationship between fasting plasma TG levels and postprandial total TRL
      TG concentrations (r = 0.79, P < 0.0001). When matched for total body fat mass,
      individuals with high levels of visceral AT (> or =130 cm2; n = 10) as assessed
      by computed tomography were characterized by increased medium- and small-TRL-TG
      responses (P < 0.05) compared with subjects with low visceral AT accumulation
      (<130 cm2; n = 10). Moreover, this elevated response of small-TRL triglycerides
      noted in men with high levels of visceral AT was not accompanied by a concomitant
      increased retinyl palmitate response in this TRL fraction, suggesting that
      visceral obesity in men is accompanied by higher postprandial VLDL production
      than is found in obese men with lower levels of visceral AT. Increased
      postprandial insulin and free fatty acid (FFA) responses were also noted in men
      with high levels of visceral AT. Finally, postheparin plasma lipoprotein lipase
      activity was negatively correlated with the total-TRL-TG response in a subsample
      of 32 individuals (r = -0.37, P < 0.05). The results of the present study suggest
      that visceral obesity is associated with an impaired postprandial TG clearance.
      Furthermore, the exaggerated postprandial FFA response observed in subjects with
      high visceral AT suggests that visceral obesity may contribute to fasting and
      postprandial hypertriglyceridemia by altering FFA metabolism in the postprandial
      state.

PMID- 9604875
TI  - Effects of sorbitol dehydrogenase deficiency on nerve conduction in experimental
      diabetic mice.
AB  - In this report, we made use of sorbitol dehydrogenase (SDH)-deficient mutant mice
      (C57BL/LiA) to test whether there is a close correlation between the level of
      polyol accumulation and the degree of reduction in motor nerve conduction
      velocity (MNCV) associated with diabetes. The C57BL/LiA mouse has SDH deficiency
      due to a G-to-A mutation at the +1 position of intron 8, thus producing only
      aberrant SDH transcripts. These C57BL/LiA mice should have higher levels of
      polyol accumulation in the peripheral nerve because of the inability to further
      metabolize sorbitol to fructose. Here, we confirm by Western blot analysis and
      high-performance liquid chromatography that these mice lack SDH in the sciatic
      nerve and other various tissues, whereas normal mice possess SDH. These C57BL/LiA
      mice do not display any obvious phenotype that includes peripheral neuropathy in
      the normal laboratory environment and breed normally as described previously,
      although the tissues that normally contain SDH accumulate more sorbitol. This
      finding suggested that C57BL/LiA mouse strain is a valid model for studying the
      role in diabetic neuropathy of the polyol pathway, which consists of two enzymes
      aldose reductase for converting glucose to sorbitol and SDH for converting
      sorbitol to fructose. Sorbitol levels in the sciatic nerve of diabetic C57BL/10N,
      nondiabetic, and diabetic C57BL/LiA mice were increased 4.3-, 16.6-, and 38.1
      fold, respectively, above that of nondiabetic C57BL/10N. The fructose level in
      the sciatic nerve was increased 2.4-fold in diabetic C57BL/10N mice compared with
      that of nondiabetic and diabetic C57BL/LiA mice. Diabetic SDH-deficient mice
      showed an MNCV reduction similar in magnitude to that of diabetic C57BL/10N mice,
      despite greater nerve sorbitol accumulation and the lack of fructose in the
      former. The present data suggest that the levels of sorbitol and fructose in the
      sciatic nerve of mice do not correlate with the severity of MNCV deficit
      associated with diabetes.

PMID- 9604876
TI  - Hepatocyte nuclear factor 1alpha coding mutations are an uncommon contributor to
      early-onset type 2 diabetes in Ashkenazi Jews.

PMID- 9604877
TI  - Exclusion of the hepatocyte nuclear factor 4alpha as a candidate gene for late
      onset NIDDM linked with chromosome 20q.

PMID- 9604878
TI  - Variant in the regulatory subunit of phosphatidylinositol 3-kinase (p85alpha):
      preliminary evidence indicates a potential role of this variant in the acute
      insulin response and type 2 diabetes in Pima women.

PMID- 9604879
TI  - Insulin receptor substrate-2 amino acid polymorphisms are not associated with
      random type 2 diabetes among Caucasians.

PMID- 9604880
TI  - The Deutsche Nicotinamide Intervention Study: an attempt to prevent type 1
      diabetes. DENIS Group.
AB  - On the basis of the positive outcome of animal experiments, several large placebo
      controlled trials are underway and aiming for the first time at the prevention of
      an immune-mediated disease, type 1 diabetes. The first of these trials, The
      Deutsche Nicotinamide Intervention Study (DENIS), evaluated the clinical efficacy
      of high doses of nicotinamide in children at high risk for IDDM. Nicotinamide has
      been shown to protect beta-cells from inflammatory insults and to improve
      residual beta-cell function in patients after onset of IDDM. Individuals at high
      risk for developing IDDM within 3 years were identified by screening the siblings
      (age 3-12 years) of patients with IDDM for the presence of high titer (> or =20
      Juvenile Diabetes Foundation [JDF] U) islet cell antibodies. Probands (n = 55)
      were randomized into placebo and nicotinamide (slow release, 1.2 g x m(-2) x day(
      1)) receiving groups and followed prospectively in a controlled clinical trial
      using a sequential design. Rates of diabetes onset were similar in both groups
      throughout the observation period (maximum 3.8 years, median 2.1 years). This
      sequential design provides a 10% probability of a type II error against a
      reduction of the cumulative diabetes incidence at 3 years from 30 to 6% by
      nicotinamide. The trial was terminated when the second sequential interim
      analysis after the eleventh case of diabetes showed that the trial had failed to
      detect a reduction of the cumulative diabetes incidence at 3 years from 30 to 6%
      (P = 0.97). The group receiving nicotinamide exhibited decreased first-phase
      insulin secretion in response to intravenous glucose (P = 0.03). No other side
      effects were observed. We conclude that in this subgroup of diabetes-prone
      individuals at very high risk and with an assumed rapid disease progression,
      nicotinamide treatment did not cause a major decrease or delay of diabetes
      development. However, the data do not exclude the possibility of a less strong,
      but potentially meaningful, risk reduction in this cohort, or a major clinical
      effect of nicotinamide in individuals with less risk of progression to IDDM than
      studied here.

PMID- 9604881
TI  - MODY1 mutation Q268X in hepatocyte nuclear factor 4alpha allows for dimerization
      in solution but causes abnormal subcellular localization.
AB  - Recent studies have shown that mutations in the hepatocyte nuclear factor (HNF)
      4alpha gene give rise to maturity-onset diabetes of the young, type 1 (MODY1).
      HNF-4, an orphan member of the nuclear receptor superfamily, contains a DNA
      binding domain (DBD) and a putative ligand-binding domain (LBD) that can act
      independently of each other. The first MODY1 mutation identified creates a stop
      codon at amino acid 268 in the LBD of HNF-4 (Q268X) that leaves the DBD intact,
      suggesting that the mutant protein may retain some of the properties of the wild
      type protein. To determine the functional properties of this mutant, we
      constructed HNF4.Q268X and tested it in vitro and in vivo for DNA binding,
      protein dimerization, and transactivation activity. Results of an electrophoretic
      mobility shift assay showed that HNF4.Q268X neither binds DNA alone nor binds it
      as a dimer with wild-type HNF-4 (HNF4.wt). In contrast, a co-immunoprecipitation
      assay showed that HNF4.Q268X is capable of dimerizing in solution with HNF4.wt.
      Transient transfection assays, however, indicated that HNF4.Q268X does not affect
      transactivation by HNF4.wt in vivo, supporting the argument against a dominant
      negative effect. Additional results suggest that the lack of a dominant negative
      effect could be due to a striking differential subcellular localization of the
      HNF4.Q268X protein: HNF4.Q268X could be extracted from transfected cells only
      when treated with SDS. Taken together, our results suggest that the MODY1
      phenotype is due to a loss of functional HNF-4 protein that is aggravated in
      tissues that express relatively low amounts of HNF-4, such as pancreas.

PMID- 9604882
TI  - CPRF4a, a novel plant bZIP protein of the CPRF family: comparative analyses of
      light-dependent expression, post-transcriptional regulation, nuclear import and
      heterodimerisation.
AB  - Several DNA-binding proteins with conserved basic region/leucine zipper domains
      (bZIP) have been isolated from parsley. They all recognise defined ACGT
      containing elements (ACEs), including ACE(PcCHSII) in the Light Regulatory Unit
      LRU1 of the CHS promoter which confers light responsiveness. A new member of this
      Common Plant Regulatory Factor (CPRF) family, designated CPRF4a, has been cloned,
      which displays sequence similarity to HBP-1a from wheat, as well as to other
      plant bZIP proteins. CPRF4a specifically binds as a homodimer to ACE(PcCHSII) and
      forms heterodimers with CPRF1 but not with CPRF2. In adult parsley plants, CPRF2
      and CPRF4a mRNAs are found in all tissues and organs in which the chalcone
      synthase gene CHS is expressed. In protoplasts from suspension cultured cells, UV
      irradiation (290-350 nm) did not cause an increase in levels of CPRF1, CPRF2, or
      CPRF4a mRNA, whereas the corresponding CPRF proteins accumulated within 15 min of
      light treatment. Furthermore, the rapid light-mediated increase of CPRF proteins
      was insensitive to transcriptional inhibitors, suggesting that a post
      transcriptional mechanism controls CPRF accumulation. CPRFs as well as
      Arabidopsis thaliana G-box binding factors (GBFs) are selectively transported
      from the cytosol into the nucleus, as shown in an in vitro nuclear transport
      system prepared from evacuolated parsley protoplasts, indicating that cytosolic
      compounds are involved in regulated nuclear targeting of plant bZIP factors.

PMID- 9604883
TI  - Detection of nptII (kanamycin resistance) genes in genomes of transgenic plants
      by marker-rescue transformation.
AB  - We have developed a novel system for the sensitive detection of nptII genes
      (kanamycin resistance determinants) including those present in transgenic plant
      genomes. The assay is based on the recombinational repair of an nptII gene with
      an internal 10-bp deletion located on a plasmid downstream of a bacterial
      promoter. Uptake of an nptII gene by transformation restores kanamycin
      resistance. In Escherichia coli, promoterless nptII genes provided by
      electroporation were rescued with high efficiency in a RecA-dependent
      recombinational process. For the rescue of nptII genes present in chromosomal
      plant DNA, the system was adapted to natural transformation, which favours the
      uptake of linear DNA. When competent Acinetobacter sp. BD413 (formerly A.
      calcoaceticus) cells containing the mutant nptII gene on a plasmid were
      transformed with DNA from various transgenic plants carrying nptII as a marker
      gene (Solanum tuberosum, Nicotiana tabacum, Beta vulgaris, Brassica napus,
      Lycopersicon esculentum), kanamycin-resistant transformants were obtained roughly
      in proportion to the concentration of nptII genes in the plant DNA. The rescue of
      nptII genes occurred in the presence of a more than 6 x 10(6)-fold excess of
      plant DNA. Only 18 ng of potato DNA (2.5 x 10(3) genome equivalents, each with
      one copy of nptII) was required to produce one kanamycin-resistant transformant.
      These experiments and others employing DNA isolated from soil samples demonstrate
      that the system allows reliable and highly sensitive monitoring of nptII genes in
      transgenic plant DNA and in DNA from environmental sources, such as soil, without
      the need for prior DNA amplification (e.g. by PCR).

PMID- 9604884
TI  - Mms4, a putative transcriptional (co)activator, protects Saccharomyces cerevisiae
      cells from endogenous and environmental DNA damage.
AB  - mms4-1 is one of several Saccharomyces cerevisiae mutants that exhibit an
      increased sensitivity to methyl methanesulfonate (MMS), but not to UV or X-rays.
      We have isolated the MMS4 gene by functional complementation of the MMS-sensitive
      phenotype in the mms4-1 strain. The MMS4 gene encodes a 691-amino acid, 78.7-kDa
      protein. The deduced Mms4 protein does not show significant homology to any of
      the known proteins in the database. However, several putative functional domains
      suggest that it may be a nuclear protein capable of interacting with other
      proteins. Examination of the mms4delta mutant phenotype indicates that the
      mutation not only sensitizes DNA to methylating and ethylating agents, but also
      to other DNA damage that blocks DNA replication. However, the mms4delta mutant
      appears to be more sensitive to chronic treatment than to acute treatment by DNA
      damaging agents. Furthermore, the spontaneous mutation rate increases
      significantly in the mms4delta mutant. Mms4 alone, when fused to a Gal4 DNA
      binding domain, is able to activate P(GAL1)-lacZ and P(GAL1)-HIS3 reporter genes
      in a two-hybrid system; the Mms4 transactivation domain maps to the highly acidic
      N-terminal region. These results collectively suggest that Mms4 may function as a
      transcriptional (co)activator and play an important role in DNA repair and/or
      synthesis.

PMID- 9604885
TI  - Nuclear protein import, but not mRNA export, is defective in all Saccharomyces
      cerevisiae mutants that produce temperature-sensitive forms of the Ran GTPase
      homologue Gsp1p.
AB  - A series of ts mutations in the GSP1 gene of Saccharomyces cerevisiae was
      isolated by error-prone PCR. A total of 25 ts gsp1 strains was obtained. Each of
      these mutants showed between one and seven different amino acid alterations. In
      several of these ts gsp1 strains, the same amino acid residues in Gsp1p were
      repeatedly mutated, indicating that our screen for ts gsp1 mutations was
      saturating. All of the ts gsp1 strains isolated had a defect in nuclear protein
      import, but only 16 of the 25 ts gsp1 strains had a defect in mRNA export. Thus,
      Gsp1p is suggested to be directly involved in nuclear protein import, but not in
      mRNA export. Following release from alpha-factor arrest, 11 of the ts gsp1
      mutants arrested in G1; the remainder did not show any specific cell-cycle
      arrest, at 37 degrees C, the nonpermissive temperature. While the mutants that
      are defective in both mRNA export and protein import have a tendency to arrest in
      G1, there was no clear correlation between the cell cycle phenotype and the
      defects in mRNA export and nuclear protein import. Based on this, we assume that
      Ran/Gsp1p GTPase regulates the cell cycle and the nucleus/cytosol exchange of
      macromolecules through interactions with effectors that were independent of each
      other, and are differentially affected by mutation.

PMID- 9604886
TI  - The Saccharomyces cerevisiae SOM1 gene: heterologous complementation studies,
      homologues in other organisms, and association of the gene product with the inner
      mitochondrial membrane.
AB  - The small nuclear gene SOM1 of Saccharomyces cerevisiae was isolated as a
      multicopy suppressor of a mutation in the IMP1 gene, which encodes the
      mitochondrial inner membrane peptidase subunit 1 (Imp1). Analysis revealed that
      Som1 and Imp1 are components of a mitochondrial protein export system, and
      interaction between these two proteins is indicated by the genetic suppression
      data. Here we describe the identification of a gene from Kluyveromyces lactis,
      which restores respiratory function to a S. cerevisiae SOM1 deletion mutant at 28
      degrees C. The sequence of the K. lactis gene predicts a protein product of 8.1
      kDa, comprising 71 amino acid residues, with a putative mitochondrial signal
      sequence at its N-terminus. The protein is 50% identical to its S. cerevisiae
      counterpart. The expression pattern of a homologous sequence in Leishmania major
      suggests a more general role for SOM1 in mitochondrial biogenesis and protein
      sorting. The various Som1 proteins exhibit a highly conserved region and a
      remarkable pattern of cysteine residues. A protein of the expected size was
      transcribed and translated in vitro. The Som1 protein was detected in fractions
      of S. cerevisiae enriched for mitochondria and found to be associated with the
      inner mitochondrial membrane.

PMID- 9604888
TI  - Temporal profiles of appearance of DNase I hypersensitive sites associated with
      the ovine beta-lactoglobulin gene differ in sheep and transgenic mice.
AB  - The ovine milk protein beta-lactoglobulin is expressed in a distinct temporal
      pattern during lactogenesis. This expression pattern is reflected in the temporal
      profile of appearance of DNase I hypersensitive sites (HS) associated with the
      beta-lactoglobulin gene in the mammary gland. Specifically, HSIV and HSV are
      present prior to the first major increase in expression, which occurs at mid
      pregnancy, while HSI displays the converse profile, being detected after mid
      pregnancy and during lactation. The extent of DNase I digestion at HSIII,
      encompassing the promoter region, reflects the level of beta-lactoglobulin
      expression. In transgenic mouse mammary chromatin, beta-lactoglobulin transgenes
      display the same set of DNase I hypersensitive sites as in sheep mammary
      chromatin. The temporal profile, however, differs from that seen in sheep:
      notably, HSIV and HSV are detected during lactation. The fact that beta
      lactoglobulin transgenes lacking HSIV and HSV are expressed but display a reduced
      transcription rate per integrated copy is compatible with a functional role for
      these regions. This suggests that HSIV and HSV may increase the likelihood of
      high-level transgene expression.

PMID- 9604887
TI  - Functional analysis of an interspecies chimera of acyl carrier proteins indicates
      a specialized domain for protein recognition.
AB  - The nodulation protein NodF of Rhizobium shows 25% identity to acyl carrier
      protein (ACP) from Escherichia coli (encoded by the gene acpP). However, NodF
      cannot be functionally replaced by AcpP. We have investigated whether NodF is a
      substrate for various E. coli enzymes which are involved in the synthesis of
      fatty acids. NodF is a substrate for the addition of the 4'-phosphopantetheine
      prosthetic group by holo-ACP synthase. The Km value for NodF is 61 microM, as
      compared to 2 microM for AcpP. The resulting holo-NodF serves as a substrate for
      coupling of malonate by malonyl-CoA:ACP transacylase (MCAT) and for coupling of
      palmitic acid by acyl-ACP synthetase. NodF is not a substrate for beta-keto-acyl
      ACP synthase III (KASIII), which catalyses the initial condensation reaction in
      fatty acid biosynthesis. A chimeric gene was constructed comprising part of the
      E. coli acpP gene and part of the nodF gene. Circular dichroism studies of the
      chimeric AcpP-NodF (residues 1-33 of AcpP fused to amino acids 43-93 of NodF)
      protein encoded by this gene indicate a similar folding pattern to that of the
      parental proteins. Enzymatic analysis shows that AcpP-NodF is a substrate for the
      enzymes holo-ACP synthase, MCAT and acyl-ACP synthetase. Biological
      complementation studies show that the chimeric AcpP-NodF gene is able
      functionally to replace NodF in the root nodulation process in Vicia sativa. We
      therefore conclude that NodF is a specialized acyl carrier protein whose specific
      features are encoded in the C-terminal region of the protein. The ability to
      exchange domains between such distantly related proteins without affecting
      conformation opens exciting possibilities for further mapping of the functional
      domains of acyl carrier proteins (i. e., their recognition sites for many
      enzymes).

PMID- 9604889
TI  - Tdd-3, a tRNA gene-associated poly(A) retrotransposon from Dictyostelium
      discoideum.
AB  - The full-length 5218-bp sequence of the mobile genetic element Tdd-3 from
      Dictyostelium discoideum is described. Tdd-3 encodes two overlapping open reading
      frames (ORFs) flanked by non-redundant, untranslated regions. The deduced amino
      acid sequence of ORF2 is homologous to reverse transcriptases (RTs) encoded by
      the class of poly(A) retrotransposons. ORF2 also encodes a putative protein
      domain related to the family of apurinic/apyrimidinic (AP) endonucleases, whose
      retroelement-encoded homologs have recently been proposed to represent the
      integrase function of poly(A) retrotransposons. Comparison of several genomic Tdd
      3 copies revealed that element insertion is orientation specific and occurs about
      100 bp downstream of tRNA genes in the D. discoideum genome. These properties of
      Tdd-3 suggest that the element is a tRNA gene-associated poly(A) retroelement
      present in the D. discoideum genome. Analysis of several cloned cDNAs derived
      from Tdd-3-specific plus strand RNAs indicate that the element is transcribed and
      polyadenylated during the growth of D. discoideum cells.

PMID- 9604890
TI  - Switch-domain mutations in the Saccharomyces cerevisiae G protein alpha-subunit
      Gpa1p identify a receptor subtype-biased mating defect.
AB  - The response to pheromone in Saccharomyces cerevisiae involves a heterotrimeric G
      protein composed of Gpa1p (alpha subunit), Ste4p (beta) and Ste18p (gamma). The
      switch II region of G alpha subunits is involved in several protein-protein
      interactions and an intrinsic GTPase activity. To investigate the role of this
      region of Gpa1p, we have analyzed the effect of switch II mutations. The Q323
      analog in G alpha subunits and Ras is implicated in GTP hydrolysis. Mutation of
      the Q323 residue of Gpa1p resulted in constitutive activation of the pheromone
      response pathway and eliminated the ability to interact with Ste4p, consistent
      with a defect in GTPase activity. Mutation of residue A59 of Ras and the
      analogous G alphas residue has had quite different effects. The analogous Gpa1p
      G321T mutation resulted in phenotypes consistent with a less severe GTPase
      defect, but also led to an unexpected mating phenotype: mating was decreased in
      both mating types, but the defect was 1000-fold more severe in alpha cells than
      in a cells. In addition the G321T mutation resulted in an unusual pheromone
      response phenotype. We discuss the possibility that these phenotypes may reflect
      a differential role for the switch II region in activation by the a- and alpha
      factor receptors.

PMID- 9604891
TI  - Characterization of a Drosophila homologue of the 160-kDa subunit of the cleavage
      and polyadenylation specificity factor CPSF.
AB  - Processing of the 3' end of mRNA precursors depends on several proteins. The
      multisubunit cleavage and polyadenylation specificity factor (CPSF) is required
      for cleavage of the mRNA precursor as well as polyadenylation. CPSF interacts
      with the cleavage stimulatory factor complex (CstF), and this interaction
      increases the specificity of binding. Following cleavage downstream of the AAUAAA
      site, CPSF and poly(A) polymerase (PAP) are required for efficient
      polyadenylation. Recently, it has been shown that 160-kDa subunit of CPSF
      interacts directly with the 77-kDa subunit of CstF, which is homologous to the
      product encoded by the Drosophila gene su(f), and with PAP. Here we report the
      cloning and characterization of a Drosophila homologue of CPSF-160. The 1329
      amino acid dCPSF protein exhibits about 45% and 20% sequence identity,
      respectively, to its mammalian and yeast counterparts over its entire length. We
      show that the CPSF homologue is expressed throughout development and that CPSF is
      essential for viability. Mutations in the cpsf gene did not alter the phenotype
      of homozygous su(f) mutations, suggesting that, for most genes, processing of 3'
      termini is not sensitive to small changes in cpsf and su(f) dosage.

PMID- 9604892
TI  - Identification of a sodium chloride-regulated promoter in Lactococcus lactis by
      single-copy chromosomal fusion with a reporter gene.
AB  - An integration vector, pORI13, was developed to screen in Lactococcus lactis for
      expression signals induced by changes in the environment and to assay
      transcriptional activity of genes in single copy. The plasmid carries a
      promoterless Escherichia coli lacZ gene preceded by a start codon, a lactococcal
      ribosome binding site, and a multiple cloning site. Chromosomal Sau3AI fragments
      of L. lactis MG1363 DNA were cloned in pORI13 using a RepA+ E. coli as host. The
      resulting bank of plasmids was used for Campbell-type integration into the
      chromosome of L. lactis MG1363. The relatively large size of the chromosomal
      fragments used increases the chance of retaining complete genes in the targeted
      region. Screening of integrants in the presence of 0.3 M NaCl resulted in the
      isolation of a clone (NS3) in which expression of lacZ was dependent on the
      concentration of chloride ions.

PMID- 9604893
TI  - Deletion of the Saccharomyces cerevisiae gene RAD30 encoding an Escherichia coli
      DinB homolog confers UV radiation sensitivity and altered mutability.
AB  - The dinB gene of Escherichia coli is an SOS-inducible gene of unknown function.
      Its mode of regulation and the amino acid sequence similarity of the predicted
      DinB protein to the UmuC protein of E. coli both suggest a role in cellular
      responses to DNA damage and probably in error-prone repair. Proteins with
      sequence similarity to DinB have been predicted from genes cloned from various
      prokaryotic and eukaryotic organisms, including Caenorhabditis elegans. Here we
      present the phenotypic characterization of a haploid Saccharomyces cerevisiae
      strain deleted for the ORF YDR419W, encoding a yeast DinB homolog. The deletion
      mutant is viable but is moderately sensitive to killing following exposure to
      ultraviolet (UV) radiation. Hence, we have named the gene RAD30. Steady-state
      levels of RAD30 transcripts are increased following UV irradiation. UV-induced
      locus-specific reversion of an ochre allele (arg4-17) is reduced in the rad30
      deletion mutant. However, enhanced mutability was observed following treatment
      with the alkylating agent methylmethanesulfonate (MMS). Spontaneous mutability
      was also slightly increased. We conclude that RAD30 encodes an accessory function
      involved in DNA repair and mutagenesis. We speculate that the relatively weak
      phenotype and the opposite effects on mutability as a function of the type of DNA
      damage involved may derive from a functional redundancy of yeast proteins which
      facilitate replicative bypass of non-coding DNA lesions.

PMID- 9604895
TI  - Regulatory concerns at various phases of drug development.

PMID- 9604894
TI  - A gene, yaeQ, that suppresses reduced operon expression caused by mutations in
      the transcription elongation gene rfaH in Escherichia coli and Salmonella
      typhimurium.
AB  - RfaH is a specialised transcription elongation protein. We isolated from a
      Salmonella typhimurium rfaH suppressor strain a gene that complements in trans
      the attenuated transcription of the hlyCABD hemolysin operon caused by an rfaH
      mutation. The gene is homologous to the uncharacterised Escherichia coli gene
      yaeQ. YaeQ did not increase hlyCABD-encoded hemolysin activity in the RfaH+ wild
      type, nor did it increase the level of RfaH protein. YaeQ also complements a
      rfaH::Tn5 null mutation, indicating that it compensates for loss of RfaH function
      without interaction between the two proteins.

PMID- 9604897
TI  - Investigational new drug applications: the role of the preclinical dossier.

PMID- 9604896
TI  - The challenge of regulating development and approval of drugs with pleiotropic
      action in cardiovascular disease.

PMID- 9604898
TI  - Early efficacy and safety studies.

PMID- 9604899
TI  - Methods and endpoint issues in clinical development of lipid-acting agents with
      pleiotropic effects.

PMID- 9604900
TI  - Efficacy and safety in Phase II trials.

PMID- 9604901
TI  - Guidelines for methods to determine efficacy and safety of drugs acting on the
      gastrointestinal tract. The international union of pharmacology (IUPHAR).

PMID- 9604902
TI  - Guidelines for approval of anti-obesity drugs affecting atherosclerosis and/or
      lipids. The international union of pharmacology (IUPHAR).

PMID- 9604903
TI  - Requirements and methods for documenting diet uniformity and compliance in drug
      development trials.

PMID- 9604904
TI  - Potential stifling effects of pharmaco-economics and regulatory policies.

PMID- 9604905
TI  - Evaluation of lipoproteins/apolipoproteins as therapeutic agents for the
      treatment of vascular and nonvascular disease.

PMID- 9604906
TI  - Use of apolipoprotein parameters and endpoints in drug development and approval
      processes.

PMID- 9604907
TI  - Documentation of efficacy of drugs affecting apoptosis and other atheroma-related
      mechanisms.

PMID- 9604908
TI  - Basic requirements for investigational new drug and new drug application approval
      for an antioxidant compound in cardiovascular disease.

PMID- 9604909
TI  - Inclusion of lipoprotein subfractions among efficacy parameters.

PMID- 9604910
TI  - Requirements for claims of favorable effects on serum lipids by oral antidiabetic
      agents.

PMID- 9604911
TI  - Clinical trial assessment of lipid-acting drugs in diabetic patients.

PMID- 9604912
TI  - Guidelines for trials of gene therapy and somatic gene therapy in cardiovascular
      disease.

PMID- 9604913
TI  - Recommendations for Phase IV studies in the development of lipid-lowering drugs.

PMID- 9604914
TI  - Phase III and Phase IV trials: noninvasive assessment of efficacy endpoints in
      vessel walls.

PMID- 9604915
TI  - Relation of angiographic and ultrasound assessment of plaque progression to
      clinical outcomes.

PMID- 9604916
TI  - Assessment of effects of lipid-lowering drugs on hemostasis.

PMID- 9604917
TI  - The role of the central clinical laboratory in the development of drugs for the
      treatment of cardiovascular disease by the modification of lipoprotein
      concentrations.

PMID- 9604918
TI  - Guidance for industry: over-the-counter treatment of hypercholesterolemia. The
      international union of pharmcaology (IUPHAR).

PMID- 9604919
TI  - Update on the U.S. Food and Drug Administration regulatory approach to over-the
      counter cholesterol-lowering drugs.

PMID- 9604920
TI  - What kinds of data should be available to probe the effects of nutrients, food
      supplements or vitamins on serum lipoprotein levels and/or atherosclerosis?

PMID- 9604921
TI  - What kinds of studies should be required to probe efficacy and safety of drugs in
      special populations?

PMID- 9604923
TI  - New twists in gene regulation by glucocorticoid receptor: is DNA binding
      dispensable?

PMID- 9604922
TI  - Should separate endpoint trials be required for all lipid-lowering drugs acting
      by the same mechanism?

PMID- 9604924
TI  - Floral induction and florigen.

PMID- 9604925
TI  - PDZ proteins organize synaptic signaling pathways.

PMID- 9604926
TI  - A Notch affair.

PMID- 9604927
TI  - The Drosophila Fab-7 chromosomal element conveys epigenetic inheritance during
      mitosis and meiosis.
AB  - Polycomb group (PcG) and trithorax group (trxG) gene products are responsible for
      the maintenance of repressed and active expression patterns of many
      developmentally important regulatory genes including the homeotic genes. In
      Drosophila embryos, Polycomb protein and the trxG protein GAGA factor colocalize
      at the Fab-7 DNA element of the bithorax complex. In transgenic lines, the Fab-7
      element induces extensive silencing on a flanking GAL4-driven lacZ reporter and
      mini-white genes. However, a short single pulse of GAL4 during embryogenesis is
      sufficient to release PcG-dependent silencing from the transgene. Such an
      activated state of Fab-7 is mitotically inheritable through development and can
      be transmitted in a GAL4-independent manner to the subsequent generations through
      female meiosis. Thus, Fab-7 is a switchable chromosomal element, which can convey
      memory of epigenetically determined active and repressed chromatin states.

PMID- 9604928
TI  - The C. elegans protein EGL-1 is required for programmed cell death and interacts
      with the Bcl-2-like protein CED-9.
AB  - Gain-of-function mutations in the Caenorhabditis elegans gene egl-1 cause the HSN
      neurons to undergo programmed cell death. By contrast, a loss-of-function egl-1
      mutation prevents most if not all somatic programmed cell deaths. The egl-1 gene
      negatively regulates the ced-9 gene, which protects against cell death and is a
      member of the bcl-2 family. The EGL-1 protein contains a nine amino acid region
      similar to the Bcl-2 homology region 3 (BH3) domain but does not contain a BH1,
      BH2, or BH4 domain, suggesting that EGL-1 may be a member of a family of cell
      death activators that includes the mammalian proteins Bik, Bid, Harakiri, and
      Bad. The EGL-1 and CED-9 proteins interact physically. We propose that EGL-1
      activates programmed cell death by binding to and directly inhibiting the
      activity of CED-9, perhaps by releasing the cell death activator CED-4 from a CED
      9/CED-4-containing protein complex.

PMID- 9604929
TI  - DNA binding of the glucocorticoid receptor is not essential for survival.
AB  - Transcriptional regulation by the glucocorticoid receptor (GR) is essential for
      survival. Since the GR can influence transcription both through DNA-binding
      dependent and -independent mechanisms, we attempted to assess their relative
      importance in vivo. In order to separate these modes of action, we introduced the
      point mutation A458T into the GR by gene targeting using the Cre/loxP system.
      This mutation impairs dimerization and therefore GRE-dependent transactivation
      while functions that require cross-talk with other transcription factors, such as
      transrepression of AP-1-driven genes, remain intact. In contrast to GR-/- mice,
      these mutants termed GRdim are viable, revealing the in vivo relevance of DNA
      binding-independent activities of the GR.

PMID- 9604930
TI  - The DHR78 nuclear receptor is required for ecdysteroid signaling during the onset
      of Drosophila metamorphosis.
AB  - Pulses of ecdysteroids direct Drosophila through its life cycle by activating
      stage- and tissue-specific genetic regulatory hierarchies. Here we show that an
      orphan nuclear receptor, DHR78, functions at the top of the ecdysteroid
      regulatory hierarchies. Null mutations in DHR78 lead to lethality during the
      third larval instar with defects in ecdysteroid-triggered developmental
      responses. Consistent with these phenotypes, DHR78 mutants fail to activate the
      mid-third instar regulatory hierarchy that prepares the animal for metamorphosis.
      DHR78 protein is bound to many ecdysteroid-regulated puff loci, suggesting that
      DHR78 directly regulates puff gene expression. In addition, ectopic expression of
      DHR78 has no effects on development, indicating that its activity is regulated
      post-translationally. We propose that DHR78 is a ligand-activated receptor that
      plays a central role in directing the onset of Drosophila metamorphosis.

PMID- 9604931
TI  - The interpretation of position in a morphogen gradient as revealed by occupancy
      of activin receptors.
AB  - Xenopus blastula cells activate different mesodermal genes as a concentration
      dependent response to activin, which behaves like a morphogen. To understand how
      cells recognize morphogen concentration, we have bound naturally labeled activin
      to cells and related this to choice of gene activation. We find that the
      increasing occupancy of a single receptor type can cause cells to switch gene
      expression. Cells sense ligand concentration by the absolute number of occupied
      receptors per cell (100 and 300 molecules of bound activin induce Xbra and Xgsc,
      respectively, i.e., 2% and 6% of the total receptors) and not by a ratio of
      occupied to unoccupied receptors. The long duration of occupancy explains a
      previously described ratchet effect. Our results suggest a new concept of
      morphogen gradient formation and interpretation that is particularly well suited
      to the needs of early development.

PMID- 9604932
TI  - MAP kinase signaling specificity mediated by the LIN-1 Ets/LIN-31 WH
      transcription factor complex during C. elegans vulval induction.
AB  - The let-23 receptor/mpk-1 MAP kinase signaling pathway induces the vulva in C.
      elegans. We show that MPK-1 directly regulates both the LIN-31 winged-helix and
      the LIN-1 Ets transcription factors to specify the vulval cell fate. lin-31 and
      lin-1 act genetically downstream of mpk-1, and both proteins can be directly
      phosphorylated by MAP kinase. LIN-31 binds to LIN-1, and the LIN-1/LIN-31 complex
      inhibits vulval induction. Phosphorylation of LIN-31 by MPK-1 disrupts the LIN
      1/LIN-31 complex, relieving vulval inhibition. Phosphorylated LIN-31 may also act
      as a transcriptional activator, promoting vulval cell fates. LIN-31 is a vulval
      specific effector of MPK-1, while LIN-1 acts as a general effector. The
      partnership of tissue-specific and general effectors may confer specificity onto
      commonly used signaling pathways, creating distinct tissue-specific outcomes.

PMID- 9604933
TI  - Genetic analysis of the mechanisms controlling target selection: complementary
      and combinatorial functions of netrins, semaphorins, and IgCAMs.
AB  - The molecular mechanisms controlling the ability of motor axons to recognize
      their appropriate muscle targets were dissected using Drosophila genetics to add
      or subtract Netrin A, Netrin B, Semaphorin II, and Fasciclin II alone or in
      combination. Fas II and Sema II are expressed by all muscles where they promote
      (Fas II) or inhibit (Sema II) promiscuous synaptogenesis. NetB is expressed by a
      subset of muscles where it attracts some axons and repels others. However, growth
      cones in this system apparently do not rely solely on single molecular labels on
      individual targets. Rather, these growth cones assess the relative balance of
      attractive and repulsive forces and select their targets based on the
      combinatorial and simultaneous input of multiple cues.

PMID- 9604934
TI  - The indeterminate gene encodes a zinc finger protein and regulates a leaf
      generated signal required for the transition to flowering in maize.
AB  - Flowering in plants is a consequence of the transition of the shoot apex from
      vegetative to reproductive growth in response to environmental and internal
      signals. The indeterminate1 gene (id1) controls the transition to flowering in
      maize. We show by cloning the id1 gene that it encodes a protein with zinc finger
      motifs, suggesting that the id1 gene product functions as a transcriptional
      regulator of the floral transition. id1 mRNA expression studies and analyses of
      transposon-induced chimeric plants indicate that id1 acts non-cell-autonomously
      to regulate the production of a transmissible signal in the leaf that elicits the
      transformation of the shoot apex to reproductive development. These results
      provide molecular and genetic data consistent with the florigen hypothesis
      derived from classical plant physiology studies.

PMID- 9604935
TI  - Phosphorylation of the MAP kinase ERK2 promotes its homodimerization and nuclear
      translocation.
AB  - The MAP kinase ERK2 is widely involved in eukaryotic signal transduction. Upon
      activation it translocates to the nucleus of the stimulated cell, where it
      phosphorylates nuclear targets. We find that nuclear accumulation of
      microinjected ERK2 depends on its phosphorylation state rather than on its
      activity or on upstream components of its signaling pathway. Phosphorylated ERK2
      forms dimers with phosphorylated and unphosphorylated ERK2 partners. Disruption
      of dimerization by mutagenesis of ERK2 reduces its ability to accumulate in the
      nucleus, suggesting that dimerization is essential for its normal ligand
      dependent relocalization. The crystal structure of phosphorylated ERK2 reveals
      the basis for dimerization. Other MAP kinase family members also form dimers. The
      generality of this behavior suggests that dimerization is part of the mechanism
      of action of the MAP kinase family.

PMID- 9604936
TI  - Crystal structure of the catalytic domain of the human cell cycle control
      phosphatase, Cdc25A.
AB  - Cdc25 phosphatases activate the cell division kinases throughout the cell cycle.
      The 2.3 A structure of the human Cdc25A catalytic domain reveals a small
      alpha/beta domain with a fold unlike previously described phosphatase structures
      but identical to rhodanese, a sulfur-transfer protein. Only the active-site loop,
      containing the Cys-(X)5-Arg motif, shows similarity to the tyrosine phosphatases.
      In some crystals, the catalytic Cys-430 forms a disulfide bond with the invariant
      Cys-384, suggesting that Cdc25 may be self-inhibited during oxidative stress. Asp
      383, previously proposed to be the general acid, instead serves a structural
      role, forming a conserved buried salt-bridge. We propose that Glu-431 may act as
      a general acid. Structure-based alignments suggest that the noncatalytic domain
      of the MAP kinase phosphatases will share this topology, as will ACR2, a
      eukaryotic arsenical resistance protein.

PMID- 9604937
TI  - Transcriptional fidelity and proofreading by RNA polymerase II.
AB  - We have addressed whether the intrinsic 3'-->5' nuclease activity of human RNA
      polymerase II (pol II) can proofread during transcription in vitro. In the
      presence of SII, a protein that stimulates the nuclease activity, pol II
      quantitatively removed misincorporated nucleotides from the nascent transcript
      during rapid chain extension. The basis of discrimination between the correct and
      incorrect base was the slow addition of the next nucleotide to the mismatched
      terminus. Incorporation of inosine monophosphate inhibited next nucleotide
      addition by a similar magnitude as a mismatched base. We used this finding to
      demonstrate that addition of SII to a transcription reaction dramatically altered
      the RNA base content, reflecting the stable incorporation of more "correct" (GMP)
      and fewer "incorrect" (IMP) nucleotides.

PMID- 9604938
TI  - Molecular basis of lysosomal enzyme recognition: three-dimensional structure of
      the cation-dependent mannose 6-phosphate receptor.
AB  - Targeting of newly synthesized lysosomal hydrolases to the lysosome is mediated
      by the cation-dependent mannose 6-phosphate receptor (CD-MPR) and the insulin
      like growth factor II/cation-independent mannose 6-phosphate receptor (IGF-II/CI
      MPR). The two receptors, which share sequence similarities, constitute the P-type
      family of animal lectins. We now report the three-dimensional structure of a
      glycosylation-deficient, yet fully functional form of the extracytoplasmic domain
      of the bovine CD-MPR (residues 3-154) complexed with mannose 6-phosphate at 1.8 A
      resolution. The extracytoplasmic domain of the CD-MPR crystallizes as a dimer,
      and each monomer folds into a nine-stranded flattened beta barrel, which bears a
      striking resemblance to avidin. The distance of 40 A between the two ligand
      binding sites of the dimer provides a structural basis for the observed
      differences in binding affinity exhibited by the CD-MPR toward various lysosomal
      enzymes.

PMID- 9604939
TI  - Nuclear access and action of notch in vivo.
AB  - The Drosophila Notch (N) gene encodes a conserved single-pass transmembrane
      receptor that transduces extracellular signals controlling cell fate. Here, we
      present evidence that the intracellular domain of Notch gains access to the
      nucleus in response to ligand, possibly through a mechanism involving proteolytic
      cleavage and release from the remainder of the protein. In addition, our results
      suggest that signal transduction by Notch depends on the ability of the
      intracellular domain, particularly the portion containing the CDC10 repeats, to
      reach the nucleus and to participate in the transcriptional activation of
      downstream target genes.

PMID- 9604940
TI  - Dangers of delay of initiation of either thrombolysis or primary angioplasty in
      acute myocardial infarction with increasing use of primary angioplasty.
AB  - We observed treatment delays and suboptimal outcomes when beginning to treat
      patients with acute myocardial infarction (AMI) with primary angioplasty. Of the
      37 patients treated during a 12-month period, 12 (32%) required either emergency
      bypass surgery or died. Delayed time intervals to balloon reperfusion (mean 134
      minutes) probably contributed to these adverse outcomes, with hemodynamic
      instability requiring pressors or intra-aortic balloon pumping in 15 patients, 12
      (75%) before the first balloon inflation. Eleven of the 12 patients with
      significant adverse outcomes required such intervention. As angioplasty use
      increased, time intervals to thrombolysis in those not treated with angioplasty
      increased from an average of 29 minutes (53% treated less than the national
      standard of 30 minutes) to 39 minutes (32% treated <30 minutes, p <0.001). During
      the last 2 months of the study period, the time intervals had increased to 48
      minutes (14% treated <30 minutes, p <0.0001). There was no change in thrombolytic
      time intervals at a local community hospital that did not offer primary
      angioplasty. Emergency Department physician confusion about the best therapy
      (angioplasty or thrombolysis) was documented in the medical records in 42% of
      cases (53 of 127). Confusion regarding therapy of AMI led to unacceptable delays
      in the administration of thrombolytic agents and probably contributed to the
      adverse outcomes in patients receiving primary angioplasty.

PMID- 9604941
TI  - Effects of aspirin on angiotensin-converting enzyme inhibition and left
      ventricular dilation one year after acute myocardial infarction.
AB  - There are conflicting reports on the interaction of aspirin with angiotensin
      converting enzyme inhibitors in heart failure and systemic hypertension. A post
      hoc analysis of the Captopril and Thrombolysis Study (CATS) study was conducted.
      At randomization, 94 patients (31.5%) took aspirin. In patients who took aspirin,
      the cumulative alpha-hydroxy butyrate dehydrogenase release was 1,151 +/- 132
      IU/L in patients randomized to captopril compared with 1,401 +/- 136 IU/L in
      patients randomized to placebo (difference -250 +/- 189 [95% confidence interval
      (CI) -620 to 120]). This difference was comparable to the difference in patients
      who did not use aspirin (-199 +/- 147 [95% CI -488 to 897]). One year after acute
      myocardial infarction, an increase in left ventricular end-diastolic volume index
      of 2.2 +/- 3.0 ml/m2 in captopril-treated and 1.9 +/- 2.9 ml/m2 in placebo
      treated patients was observed in patients who took aspirin (difference 0.4 +/-
      4.2 [95% CI -8.2 to 8.9]). This difference was also comparable to the difference
      in patients who did not take aspirin (2.2 +/- 3.8 [95% CI -5.2 to 9.7]). One year
      after acute myocardial infarction, patients who did take aspirin had a mean
      change in LV end-diastolic volume index of 2.1 +/- 2.1 ml/m2 compared with 8.4 +/
      1.9 ml/m2 in patients who did not use aspirin (p = 0.02). Thus, aspirin does not
      attenuate the acute and long-term effects of angiotensin-converting enzyme
      inhibition after acute myocardial infarction, but independently reduces LV
      dilation after myocardial infarction.

PMID- 9604942
TI  - Electrocardiographic and clinical predictors of acute myocardial infarction in
      patients with unstable angina pectoris.
AB  - Among patients with unstable angina pectoris (UAP), those who have non-ST
      elevation acute myocardial infarction (AMI) are at higher risk for subsequent
      adverse events. To determine predictors of AMI in patients with UAP, we studied
      consecutive nonreferral patients with UAP or AMI admitted from the emergency
      department to the intensive care or telemetry units of an urban teaching hospital
      over 1 year. There were 280 study patients (mean age 66 years, 1/3 women); 24%
      had AMI at presentation, whereas 76% had UAP without evidence of AMI. Thresholds
      of > or = 3 involved leads (odds ratio [OR] 3.3; 95% confidence intervals [CI]
      1.6 to 6.9) and > or = 0.2 mV (OR 5.1; 95% CI 2.2 to 11.6) of ST depression on
      the presenting electrocardiogram were strongly associated with AMI. The
      multivariate predictors of AMI were reported duration of symptoms >4 hours (OR
      3.8; 95% CI 1.9 to 7.3), absence of prior revascularization (OR 3.5; 95% CI 1.6
      to 7.5), absence of beta-blocker use before presentation (OR 2.8; 95% CI 1.3 to
      5.8), and presence of new ST depression (OR 2.8; 95% CI 1.4 to 5.7). Using the 4
      multivariate predictors, a prediction rule was developed. The percentages of
      patients with AMI when 0, 1, 2, 3, or 4 characteristics were present,
      respectively, were 7%, 6%, 24%, 46%, and 83% (p <0.001). A similar prediction
      rule developed from the Thrombolysis In Myocardial Ischemia III trial was
      validated in our cohort. Among patients with UAP, electrocardiographic and
      clinical variables can help immediately identify those at high risk for AMI at
      presentation.

PMID- 9604943
TI  - Howard Bertram Burchell, MD: a conversation with the editor. Interview by William
      C. Roberts.

PMID- 9604944
TI  - Structural constriction of the artery wall contributes to stenosis severity in
      unstable angina.
AB  - Eight consecutive patients with unstable angina underwent intravascular
      ultrasound imaging of the culprit artery with measurements recorded at the
      stenosis and at an adjacent reference site. In all patients, total artery cross
      sectional area was smaller at the stenosis site than at the reference site,
      indicating that a structural change in the artery wall due to a constrictive
      process appears to contribute to the worsening of stenosis severity associated
      with unstable angina.

PMID- 9604945
TI  - Left atrial appendage function assessed by transesophageal echocardiography
      before and on the day after elective cardioversion for nonvalvular atrial
      fibrillation.
AB  - We investigated left atrial appendage function by transesophageal
      echocardiography, on the day after external electrical cardioversion to sinus
      rhythm, in 41 patients with nonvalvular atrial fibrillation. After cardioversion,
      appendage contraction synchronized with the electrical and mechanical activity of
      the atrium, which was restored in about 70% of the patients.

PMID- 9604946
TI  - Causes and consequences of discontinuation of the implantable cardioverter
      defibrillator therapy in non-terminally ill patients.
AB  - Infection and implantable cardioverter-defibrillator shocks are important
      contributing factors to discontinuation of cardioverter-defibrillator therapy in
      non-terminally ill patients. These patients are at a high risk of sudden cardiac
      death despite continued antiarrhythmic drug therapy.

PMID- 9604947
TI  - Diagnostic accuracy of stress thallium-201 tomography in patients with left
      ventricular hypertrophy.
AB  - Two hundred patients with echocardiographically proven left ventricular
      hypertrophy underwent quantitative stress thallium tomography. The overall
      sensitivity and specificity were high (84% and 82%, respectively).

PMID- 9604948
TI  - Comparison of plasma neurohormones in congestive heart failure patients with
      atrial fibrillation versus patients with sinus rhythm.
AB  - Plasma atrial natriuretic peptide and endothelin are further elevated in patients
      with congestive heart failure and atrial fibrillation, compared to those with
      sinus rhythm. The higher plasma endothelin suggests that vasoconstriction is an
      important mechanism for hemodynamic compensation in these patients.

PMID- 9604949
TI  - A four-minute submaximal constant work rate exercise test to assess
      cardiovascular functional class in chronic heart failure.
AB  - To develop a submaximal constant work rate exercise test able to grade
      cardiovascular dysfunction in patients with chronic heart failure, 80 patients
      and 59 control subjects performed a symptom-limited incremental exercise test and
      a constant work rate exercise test at a fixed work rate (50 W for 4 minutes). The
      time constant of VO2 at the start of constant work rate exercise and time for gas
      exchange ratio (respiratory exchange ratio) to equal 1 were independent
      predictors of cardiovascular functional class and correctly classified the
      functional class in 89 +/- 9% and 83 +/- 11% of patients, respectively.

PMID- 9604950
TI  - Echocardiographic evaluation of left ventricular systolic function in the Down
      syndrome.
AB  - Left ventricular systolic function was evaluated by echo-Doppler in 22 Down
      syndrome patients without congenital heart disease. Although they had evident
      left ventricular hyperkinesia, this did not appear to reflect intrinsic
      abnormalities of myocardial properties but a reduced afterload.

PMID- 9604951
TI  - Effect of pulmonary artery stenoses on the cardiopulmonary response to exercise
      following repair of tetralogy of Fallot.
AB  - Data from exercise tests, echocardiograms, and lung perfusion scans were analyzed
      to determine whether the excessive minute ventilation (VE) often encountered
      among patients with tetralogy of Fallot is due to ventilation-perfusion mismatch
      secondary to branch pulmonary artery stenoses. Patients with branch PA stenoses
      had lower peak oxygen consumptions and higher VE during exercise than did
      patients without stenoses, and a strong correlation existed between the degree of
      pulmonary blood flow maldistribution on lung perfusion scan and the amount of
      excessive VE during exercise.

PMID- 9604952
TI  - In vitro Doppler assessment of pressure gradients across modified Blalock-Taussig
      shunts.
AB  - The relation between flow velocity and the pressure decrease is evaluated in
      Blalock-Taussig shunts used in congenital heart surgery and is related to the
      flow conditions and geometries of the shunts studied. The authors propose that
      the flow conditions within the shunt as well as shunt dimensions need to be taken
      into account when using Doppler velocimetry to predict pressure drops across
      these shunts.

PMID- 9604953
TI  - The heart at necropsy in centenarians.
AB  - Cardiac findings at necropsy are described in 6 patients aged 100 to 103 years of
      age. Although 4 had considerably narrowed coronary arteries at necropsy, none had
      apparent clinical evidence of myocardial ischemia or congestive heart failure
      during life.

PMID- 9604954
TI  - Effects of acute cigarette smoking on endothelium-dependent arterial dilatation
      in normal subjects.
AB  - The effects of acute cigarette smoking on endothelial function were evaluated in
      the brachial artery of 10 nonsmoking healthy subjects. Endothelial dysfunction
      observed after cigarette smoking is a phenomenon lasting at least 60 minutes and
      does not appear to be attenuated with repeat exposure.

PMID- 9604955
TI  - Test-retest reproducibility of maximum cardiac output by Doppler
      echocardiography.
AB  - Test-retest reproducibility of stroke volume and cardiac output using Doppler
      echocardiography was examined during maximum cycle exercise in 13 young men. A
      coefficient of variation of 8.5% and 8.1% and intraclass correlation coefficient
      of 0.90 and 0.91 for maximum stroke volume and cardiac output, respectively,
      indicate a high degree of reproducibility using this technique.

PMID- 9604956
TI  - Exercise performance and chronotropic response in heart failure patients with
      implantable left ventricular assist devices.
AB  - During metabolic stress testing, 9 of 20 patients with left ventricular assist
      devices exhibited a lag in peak device rate by < or = 85% of peak native heart
      rate (group I), with peak device rates of 118 +/- 9 beats/min compared with group
      II, in which peak device rate nearly equaled peak native rates. Peak systolic
      blood pressure was significantly greater in group II than group I, but there was
      no significant difference in peak oxygen consumption, anaerobic threshold, or
      peak flows.

PMID- 9604957
TI  - Prevalence and effects of cardiac rehabilitation on depression in the elderly
      with coronary heart disease.
AB  - Depression is a prevalent condition in coronary patients and is associated with
      increased morbidity and mortality following major coronary events. We measured
      the prevalence of depressive symptoms in 268 elderly coronary patients 4 to 6
      weeks following a major coronary event and assessed its modulation by outpatient
      cardiac rehabilitation and found that cardiac rehabilitation resulted in a
      significant reduction in the prevalence and severity of this disorder.

PMID- 9604958
TI  - Heterogeneity of prognosis in patient subsets treated by primary coronary
      angioplasty during acute myocardial infarction.
AB  - Among 377 patients consecutively treated with primary coronary angioplasty for
      acute myocardial infarction, in-hospital mortality was higher in patients
      ineligible than in patients eligible for thrombolysis (14.4% vs 7.8%, p <0.05).
      It remained dismal (75.9%) in patients with cardiogenic shock, but was similar in
      lytic-eligible patients and in those who were ineligible because of an increased
      bleeding risk (7.8% vs 7.2%, p = NS), and was zero in patients with nondiagnostic
      electrocardiograms.

PMID- 9604960
TI  - Aortic hypoplasia in homozygous familial hypercholesterolemia.
AB  - Diagnosis of hypoplastic aortic root with ultrafast computed tomography provides
      important clinical information in homozygous familial hypercholesterolemic
      patients with supravalvular aortic stenosis.

PMID- 9604959
TI  - Significance of development of late potentials after anterior wall acute
      myocardial infarction despite successful primary angioplasty of the left anterior
      descending coronary artery.
AB  - We classified 33 patients with a first anterior infarction and single-vessel
      disease who had undergone successful primary angioplasty and had a patent infarct
      related artery into groups based on the development of late potentials. Left
      ventricular function improved between 1 and 3 months after angioplasty only in
      patients without late potentials; the development of late potentials after acute
      anterior infarction was associated with prolonged left ventricular dysfunction
      despite successful revascularization with primary angioplasty.

PMID- 9604961
TI  - Aerobic and myocardial demands of lawn mowing in patients with coronary artery
      disease.
AB  - Lawn mowing approximates 4 to 6 METs and may evoke heart rate and systolic blood
      pressure responses that approach and exceed those attained during maximal
      exercise testing. The excessive cardiac demands may be deceptively camouflaged by
      the moderate aerobic requirements and perceived effort.

PMID- 9604962
TI  - Baseline serum total cholesterol and coronary heart disease incidence in African
      American women (the NHANES I epidemiologic follow-up study). National Health and
      Nutrition Examination Survey.
AB  - Proportional-hazards analyses for African-American women aged 25 to 74 revealed a
      variable association of coronary heart disease risk with baseline serum total
      cholesterol (after adjusting for age fifth vs first quintile: RR = 1.62, 95%
      confidence interval [CI] 0.89 to 2.98, p = 0.12; after adjusting for age,
      systolic blood pressure, body mass index, smoking, history of diabetes, low
      education, and low family income: RR = 1.88, 95% CI 1.02 to 3.45, p = 0.04).
      Perhaps due to the relatively small number of events, the association of serum
      total cholesterol with coronary heart disease incidence in African-American women
      was not consistently significant.

PMID- 9604963
TI  - Relation of left atrial spontaneous echo contrast with prethrombotic state in
      atrial fibrillation associated with systemic hypertension, idiopathic dilated
      cardiomyopathy, or no identifiable cause (lone).
AB  - To investigate the association of left atrial (LA) spontaneous echo contrast with
      the hemostatic state in nonrheumatic atrial fibrillation (AF), we examined the
      plasma levels of prothrombin fragment 1+2 and fibrinopeptide A in 73 patients
      with chronic nonrheumatic AF undergoing transesophageal echocardiography and 38
      age-matched normal subjects. The results support the theory that LA spontaneous
      echo contrast in nonrheumatic AF is associated with a hypercoagulable state,
      especially in patients with marked LA spontaneous echo contrast.

PMID- 9604964
TI  - Clinical efficacy of the wearable cardioverter-defibrillator in acutely
      terminating episodes of ventricular fibrillation.
AB  - The findings of our initial study demonstrate for the first time the ability to
      terminate induced VT/VF reliably (100% of all episodes) by a single, monophasic
      230-J shock delivered by the Wearable Cardioverter-Defibrillator (WCD). Although
      limited by sample size, our data suggest the WCD could be used as a feasible
      bridge to definitive implantation of an implantable cardioverter-defibrillator in
      patients in whom risk stratification for sudden death is not completed.

PMID- 9604965
TI  - Frequency of neurologic complications following carotid sinus massage.
AB  - Carotid sinus massage is a useful procedure in diagnosis and treatment. A
      standard technique with applied exclusion criteria causes infrequent neurologic
      complications (11 in 16,000), most of which are transient and result in full
      recovery.

PMID- 9604966
TI  - Comparison between echocardiographic subtraction method and first-pass
      radionuclide ventriculography for measuring right ventricular volume after
      operative "repair" of patients with tetralogy of Fallot.
AB  - In the long-term follow-up of patients after repair of tetralogy of Fallot,
      monitoring right ventricular function is mandatory. The echocardiographic
      subtraction method proposed by Tomita seems to be easily applicable to a
      pediatric age population and accurate enough to be included in the longitudinal
      surveillance of such a group of patients.

PMID- 9604967
TI  - Effect of suture closure of coronary artery fistula on aneurysmal coronary artery
      and myocardial ischemia.
AB  - This study indicates the importance of coronary angiography and myocardial
      scintigraphy on long-term follow-up of patients after surgery for coronary
      arterial fistula in view of the progression to coronary artery obstruction and
      myocardial ischemia.

PMID- 9604968
TI  - Impact of injection rate on the Thrombolysis in Myocardial Infarction (TIMI)
      trial frame count.
AB  - A mechanical injection was used to determine the impact of injection rate on the
      TIMI frame count. The 1.0-ml/s increase in hand injection rates from the 10th to
      90th percentiles for angiographers is associated with a minor decrease of <2
      frames that is <7% of the corrected TIMI frame count.

PMID- 9604969
TI  - Supravalvular aortic stenosis in aortic dissection.
AB  - Supravalvular aortic stenosis is a rare complication of aortic dissection. We
      report on echocardiographic and magnetic resonance observations in 2 cases of
      aortic dissection with false lumen thrombosis of the ascending aorta and severe
      narrowing of the true lumen.

PMID- 9604970
TI  - Interventional therapeutic procedures in patients with a preexisting dual site
      right atrial pacing system for refractory atrial fibrillation.
AB  - This report illustrates the complexity of internal atrial defibrillation and
      implantable cardioverter-defibrillator therapy in patients with dual site atrial
      pacing systems.

PMID- 9604971
TI  - Marked left ventricular hypertrophy in children on tacrolimus (FK506) after
      orthotopic liver transplantation.
AB  - Although the cardiac effects of tacrolimus (FK506) have not been well documented,
      clinical cases of children on FK506 who developed hypertrophic obstructive
      cardiomyopathy have been reported. We report 2 cases of marked concentric
      hypertrophy of the left ventricular myocardium found at autospy in children on
      FK506.

PMID- 9604972
TI  - Can we be faithful to the Hippocratic oath in the era of managed care?

PMID- 9604973
TI  - Progressive sensorineural hearing loss and a widened vestibular aqueduct in
      Pendred syndrome.
AB  - Pendred syndrome is an autosomal recessive inherited disorder. Obligatory
      features are profound deafness in childhood and defective organic binding of
      iodine in the thyroid gland. Therefore, goiter is a common symptom. Hypoplasia of
      the cochlea is another feature. Recently, the gene for Pendred syndrome was
      identified. We describe a boy whose sensorineural hearing loss in both ears
      progressed rapidly from about 50 to 60 dB at the age of 3 years and 3 months to
      more than 100 dB at the age of 4 years and 4 months. This loss was preceded by a
      medical history of a progressive hearing loss. The progressive nature of the
      hearing loss motivated a search for the cause. Dysplasia of the cochlea and a
      widened vestibular aqueduct were found. The results of thyroid function tests
      were normal, but he had an elevated level of thyroglobulin. The diagnosis of
      Pendred syndrome was confirmed by the positive results of a potassium perchlorate
      test, indicating defective organic binding of iodine in the thyroid gland. It is
      possible that the widened vestibular aqueduct was responsible for the increase in
      the hearing impairment. Aside from the branchio-otorenal syndrome, Pendred
      syndrome is the only other known genetic disorder with a widened vestibular
      aqueduct. If a child has progressive sensorineural deafness and a widened
      vestibular aqueduct, it is important to consider a diagnosis of Pendred syndrome.
      A widened vestibular aqueduct may help to elucidate the pathophysiologic
      characteristics of hearing loss in these genetic types of deafness in childhood.

PMID- 9604974
TI  - Air bag deployment and hearing loss.

PMID- 9604975
TI  - Vestibular evoked myogenic potentials in patients with acoustic neuromas.
AB  - BACKGROUND: To diagnose acoustic neuromas (ANs), the auditory brainstem response
      test and the caloric test have been used in addition to magnetic resonance
      imaging. The auditory brainstem response and the caloric tests mainly reflect
      functions of the auditory pathway, ie, the cochlear nerve and the superior
      vestibular nerve, respectively. Because the vestibular evoked myogenic potential
      (VEMP) has been thought to originate in the inferior vestibular nerve, we
      hypothesized that the VEMP could provide different information from the auditory
      brainstem response and the caloric test and that it could be helpful in
      diagnosing ANs. In other words, we hypothesized that the VEMP could provide
      information concerning inferior vestibular nerve involvement in patients with
      ANs. OBJECTIVE: To find out if the VEMP could be useful in classifying ANs
      according to the involved nerves. DESIGN: We reviewed preoperative clinical
      tests, including VEMPs, in 21 patients (8 men, 13 women) with ANs confirmed
      surgically and histopathologically, comparing them with VEMPs in 8 normal
      subjects (5 men, 3 women). RESULTS: Whereas the first positive-negative peak of
      the VEMP, P13-N23, was ipsilaterally present on stimulation of the unaffected
      side in all patients with ANs and both sides in all normal subjects, it was
      absent on the affected side in 15 patients (71%) and significantly decreased in
      amplitude in 2 patients (9%). Thus, 17 (80%) of the 21 patients showed abnormal
      VEMPs. Three patients had abnormal VEMPs although they had normal caloric
      responses. Three patients had abnormal caloric responses although they had normal
      VEMPs. CONCLUSION: These results suggest that the VEMP could be useful for the
      diagnosis of AN, especially for classifying ANs according to the involved nerves.

PMID- 9604976
TI  - Effect of fluticasone in severe polyposis.
AB  - OBJECTIVES: To investigate the effect of intranasal corticosteroids in the
      treatment of polyps in patients with severe polyposis listed for surgical
      treatment and to determine the treatment effect on the progression of the
      disease. DESIGN: A double-blind, randomized, parallel-group, placebo-controlled,
      12-week study at a single center. SETTING: A tertiary referral center in London,
      England. PATIENTS: Thirty-four patients with severe polyposis listed for
      endoscopic surgical treatment. INTERVENTION: By random allocation, fluticasone
      propionate aqueous nasal spray (FPANS), 200 microg twice a day; beclomethasone
      dipropionate aqueous nasal spray, 200 microg twice a day; or placebo nasal spray
      twice a day was administered. Patients received 2 actuations to each nostril in
      the morning and in the evening. MAIN OUTCOME MEASURES: Efficacy end points were
      the need for polypectomy at the end of treatment, the results of acoustic
      rhinometry, the polyp score, the peak nasal inspiratory flow rate, and an
      assessment of symptoms. RESULTS: The polyp score was significantly decreased in
      the FPANS-treated group (P < or = .01). The nasal cavity volume was significantly
      increased in both the FPANS-treated group and the group receiving beclomethasone
      compared with placebo (P < or = .01) at the end of treatment. The percentage
      change in the mean morning peak nasal inspiratory flow rate was greater in the
      FPANS-treated group, with a significant effect observed at week 2 (P = .01).
      Nasal blockage was significantly decreased in both active groups compared with
      the group receiving placebo. No significant difference was observed between the
      treatment groups in the number of patients requiring polypectomy. CONCLUSIONS:
      Fluticasone and beclomethasone aqueous nasal sprays are effective in treating the
      symptoms of severe nasal polyps. There was some evidence that the group treated
      with FPANS responded more quickly to intervention and that the magnitude of the
      response was greater than in the group receiving beclomethasone.

PMID- 9604977
TI  - An approach to fulminant invasive fungal rhinosinusitis in the immunocompromised
      host.
AB  - OBJECTIVE: To examine the pathogenesis of fulminant invasive fungal
      rhinosinusitis to determine factors that may affect patient survival. METHODS:
      Retrospective chart review of 25 patients treated for invasive fungal
      rhinosinusitis over a 10-year period at an academic tertiary referral center.
      Evaluation of the medical and surgical records, radiographic studies, surgical
      pathology specimens, and culture results allowed for a multifactorial comparison
      between survivors and nonsurvivors. Survivors were patients who left the hospital
      with the invasive fungal disease stable or cured. RESULTS: Fungal invasion often
      occurs within the nasal cavity (92% of patients), most commonly at the middle
      turbinate (62% of patients receiving biopsy). Survivors had complete surgical
      resection more often than nonsurvivors (90% vs 0%), and were more likely to
      respond to granulocyte colony-stimulating factor than nonsurvivors (100% vs 0% of
      those treated). CONCLUSIONS: Rigid nasal endoscopy with frozen section biopsy of
      suspicious nasal lesions and high-incidence areas (ie, middle turbinate) allows
      for the timely diagnosis of invasive fungal rhinosinusitis. Survival improves if
      the disease is limited to the nasal or sinus cavities, which may represent an
      earlier stage of disease. Favorable prognostic signs include the ability to
      achieve a complete surgical resection and a positive response to granulocyte
      colony-stimulating factor in the neutropenic patient.

PMID- 9604978
TI  - Sensorineural hearing loss in children after liver transplantation.
AB  - OBJECTIVE: To investigate risk factors for sensorineural hearing loss (SNHL) in
      children after liver transplantation. DESIGN: Retrospective medical record
      review. SETTING: Pediatric tertiary care hospital. PATIENTS: One hundred twenty
      five consecutive children who received liver transplants between March 1, 1987,
      and June 30, 1996. MAIN OUTCOME MEASURES: The presence of SNHL (bone conduction
      threshold of >35 dB of hearing loss in at least 1 frequency) and the cause of the
      liver abnormality in all 125 patients. In addition, among the subset of children
      who had biliary atresia and underwent transplantation before 2 years of age, the
      total dose (milligrams per kilogram of body weight) of aminoglycoside antibiotic
      medications (tobramycin sulfate, gentamicin sulfate, and amikacin sulfate) and of
      intravenous loop diuretic agents (furosemide) was compared between children with
      and without SNHL. RESULTS: Audiologic evaluations were available for 66 of 125
      patients, 15 (12%) of whom have SNHL. Of 5 survivors with the short-bowel
      syndrome, 4 have severe to profound SNHL. Of 46 children who have biliary atresia
      and who underwent transplantation before 2 years of age, 8 (17%) have SNHL. Among
      the 26 evaluable children with biliary atresia undergoing liver transplantation
      before 2 years of age, logistic regression analysis revealed that the most
      important risk factor for SNHL was the cumulative dose of amikacin (P = .05).
      CONCLUSIONS: Children receiving liver transplants are at an increased risk for
      SNHL. Those with the short-bowel syndrome have the greatest prevalence of SNHL.
      Among the subset of children with biliary atresia receiving liver transplants
      before 2 years of age, statistical analysis demonstrates a dose-response
      relationship between the receipt of amikacin and the occurrence of SNHL.

PMID- 9604979
TI  - Transnasal endoscopic repair of congenital choanal atresia: long-term results.
AB  - OBJECTIVE: To evaluate the short- and long-term success of the repair of
      congenital choanal atresia using the transnasal endoscopic approach with and
      without power instruments. DESIGN AND SETTING: Retrospective case series in a
      tertiary care center. PATIENTS: Fifteen patients with either unilateral or
      bilateral congenital choanal atresia were treated using the transnasal endoscopic
      approach. Postoperative stenting was used in all 15 patients. INTERVENTIONS: The
      senior surgeon (C.W.G.) currently uses the transnasal endoscopic drill-out
      technique. We describe our experience and long-term follow-up of 15 patients (9
      with unilateral atresia, 5 with bilateral atresia, and 1 with unilateral
      stenosis) who were treated with the use of the transnasal endoscopic technique
      during a 7-year period. In 8 patients, the transnasal endoscopic technique was
      performed using conventional biting instruments, and in 7 patients, the
      transnasal endoscopic technique with power instruments was used. MAIN OUTCOME
      MEASURE: The patency of the surgical repair of congenital choanal atresia by the
      transnasal endoscopic approach. RESULTS: Of 14 patient procedures, 12 remained
      patent. One patient required minor debridement of granulation tissue 1 week
      following stent removal, and 1 patient required surgical transnasal revision 2
      months after the primary procedure, with a patent result after the second
      procedure. Despite patent choanae being achieved, 1 patient died of cardiac
      anomalies 8 months after the atresia repair. CONCLUSIONS: The transnasal
      endoscopic route offers excellent visualization of the posterior choana and,
      hence, the ability to open the defect widely with a high surgical success rate.
      Newer powered instrumentation further enhances the ability to perform this
      technique cleanly.

PMID- 9604980
TI  - S-phase fraction as a predictor of prognosis in juvenile respiratory
      papillomatosis.
AB  - OBJECTIVE: To determine whether DNA ploidy and the S-phase fraction are
      predictive of the clinical course in children with recurrent respiratory
      papillomatosis. DESIGN: Masked compression of DNA analysis findings to the
      clinical course of the disease. SETTING: Tertiary referral center. PATIENTS: All
      pediatric patients treated for recurrent respiratory papillomatosis at our
      institution between 1989 and 1995 who had adequate follow-up and whose primary
      biopsy specimen was available for examination. Fifty-five patients met these
      criteria. METHODS: Information was collected from the case notes on the patient's
      age at presentation, sex, sites of disease, duration of active disease, and
      frequency of operative interventions. Flow cytometric analysis was performed on
      the archival paraffin-embedded primary biopsy specimen obtained at the initial
      surgical excision, providing DNA content and percentages of S-phase cells. The
      investigators who performed the DNA analysis were masked to the clinical course.
      RESULTS: The age of the patients at presentation ranged from 3 months to 16
      years. Thirty patients had involvement in more than 1 anatomical site. The
      disease in 10 patients had spread to the distal tracheobronchial tree. The
      patients underwent a total of 1124 procedures, with a frequency range of 7 to 27
      per year. All cell populations studied were diploid. The percentage of S-phase
      cells was significantly higher in the primary biopsy specimen from patients with
      disease characterized by more frequent recurrences, multiple sites, and distal
      extension (P<.05). In multiple regression analysis, the S-phase fraction was
      found to be an independent and powerful prognostic factor for aggressive disease.
      CONCLUSIONS: The S-phase fraction may be predictive of the clinical course in
      patients with juvenile respiratory papillomatosis. Prospective studies are needed
      to assess the diagnostic and clinical value of our primary results and to
      determine whether DNA analysis can assist in identifying patients at increased
      risk for an aggressive clinical course.

PMID- 9604981
TI  - Results of esophageal biopsies performed during triple endoscopy in the pediatric
      patient.
AB  - BACKGROUND: Endoscopic examination (direct laryngoscopy and bronchoscopy) is the
      method of choice for diagnosis of respiratory symptoms of unknown cause in
      children. However, gastroesophageal reflux is being recognized increasingly often
      as a cause of pediatric respiratory symptoms and is difficult to diagnose on the
      basis of findings from direct laryngoscopy and bronchoscopy. In cases in which
      gastroesophageal reflux was included in the differential diagnosis, we
      additionally performed esophagoscopy with esophageal mucosal biopsies.
      OBJECTIVES: To determine the feasibility, safety, and efficacy of routinely
      performing esophageal biopsies during triple endoscopy in children. METHODS:
      Twenty-four children ranging in age from 2 weeks to 10 years were referred for
      airway evaluation. Under general anesthesia, children underwent direct
      laryngoscopy and bronchoscopy and esophagoscopy with mucosal biopsy. RESULTS:
      Esophageal mucosa biopsy specimens were quickly and safely obtained during
      endoscopic evaluation. There were no complications. Reflux esophagitis was
      present in 54% of biopsy specimens, as suggested by basal cell hyperplasia,
      papillary elongation, and/or inflammatory cell infiltrates. CONCLUSION:
      Gastroesophageal reflux is often difficult to diagnose in the pediatric
      population. When direct laryngoscopy and bronchoscopy is performed during
      examination of the child with airway symptoms, the addition of esophagoscopy with
      mucosal biopsies will safely and quickly provide data regarding the potential
      contribution of gastroesophageal reflux.

PMID- 9604982
TI  - Gastroesophageal reflux in patients with subglottic stenosis.
AB  - OBJECTIVES: To determine the incidence of gastroesophageal reflux in patients
      with subglottic stenosis (SGS) and to determine if upper esophageal reflux occurs
      in addition to lower esophageal reflux in these patients. DESIGN: Esophageal pH
      probe studies were reviewed in patients diagnosed as having SGS. SETTING: A
      tertiary care pediatric medical center. PATIENTS: All patients diagnosed as
      having SGS between January 1990 and July 1996 who had undergone monitoring with
      an overnight esophageal pH probe. Seventy-four patients qualified for the study.
      All 74 patients underwent lower probe testing, and 55 of the 74 underwent dual
      (upper and lower) probe testing. MAIN OUTCOME MEASURES: The percent of time a pH
      measurement of less than 4.0 was recorded in the upper and lower esophagus. A
      lower probe pH measurement of less than 4.0 more than 10% of the study time was
      considered high risk for developing reflux-associated pathologic symptoms. A
      lower probe pH measurement of less than 4.0 for 5% to 10% of the study time was
      considered a marginal risk for developing reflux-associated pathologic symptoms.
      Upper probe criteria for reflux-associated symptoms have not been established.
      Therefore, patients were grouped as having a pH of less than 4.0 in the upper
      esophagus for 0%, 0.1% to 0.9%, 1.0% to 1.9%, 2.0% to 3.0%, or more than 3% of
      the study time. RESULTS: Thirty-seven of the 74 patients who underwent lower
      probe testing had a pH of less than 4.0 more than 5% of the study time, and 24
      had a pH of less than 4.0 more than 10% of the study time. Twelve of the 55
      patients who underwent upper probe testing had no measurable reflux; 27 of the 55
      had a pH of less than 4.0 more than 1% of the study time; 14 had a pH of less
      than 4.0 more than 2% of the study time, and 11 had a pH of less than 4.0 more
      than 3% of the study time. CONCLUSIONS: Gastroesophageal reflux is frequently
      present in patients with SGS. Gastric contents frequently reach the upper and
      lower esophagus in these patients. In addition, the high incidence of
      gastroesophageal reflux in these patients suggests that it may play a role in the
      development of SGS. The possible effect of gastroesophageal reflux on the
      surgical repair of SGS requires further study.

PMID- 9604983
TI  - Use of a rapid intraoperative parathyroid hormone assay in the surgical
      management of parathyroid disease.
AB  - OBJECTIVE: To evaluate the utility of a rapid intraoperative parathyroid hormone
      (PTH) immunoradiometric assay in the surgical management of parathyroid disease,
      particularly with reference to limiting extent of cervical exploration. DESIGN:
      Nonrandomized prospective study. SETTING: Academic tertiary care center.
      PATIENTS: Forty-three consecutive patients undergoing parathyroid exploration for
      adenoma or hyperplasia had rapid PTH assays performed from blood drawn at
      induction and 7 minutes after resection of all hyperfunctioning parathyroid
      tissue. OUTCOME MEASURES: Excision of all hyperfunctioning parathyroid tissue as
      assessed by bilateral neck exploration, postoperative normalization of serum
      calcium and PTH levels, and resolution of clinical symptoms. RESULTS: The
      intraoperative rapid PTH assay accurately reflected whether all hyperfunctioning
      parathyroid tissue was excised in every patient. In 41 patients, all
      hyperfunctioning parathyroid tissue was resected at the time of surgery and
      confirmed by a corresponding decrease in the intraoperative postexcision rapid
      PTH determination as well as by subsequent normalization of postoperative serum
      calcium and PTH levels and resolution of clinical symptoms. In 2 patients, the
      postexcision rapid PTH assay determination was not consistent with removal of all
      hyperfunctioning parathyroid disease and both patients demonstrated persistent
      hyperparathyroidism postoperatively. CONCLUSIONS: The intraoperative rapid PTH
      assay may be of significant benefit in permitting directed unilateral parathyroid
      explorations for adenoma when combined with preoperative localization with a
      technetium-99m sestamibi scan. Additionally, the rapid PTH assay has proved to be
      of benefit in confirming excision of all hyperfunctioning parathyroid tissue in
      patients with multiple gland hyperplasia, particularly those who may harbor
      ectopic parathyroid tissue.

PMID- 9604984
TI  - Costs of posttreatment surveillance for patients with upper aerodigestive tract
      cancer.
AB  - OBJECTIVES: To determine the range of recommended follow-up strategies for
      patients with upper aerodigestive tract cancer treated with curative intent and
      to estimate the cost of follow-up. DESIGN: Economic analyses of the costs
      associated with 31 follow-up strategies (12 generic and 19 site specific)
      identified from a MEDLINE search of the literature for 1978 to 1997 and a search
      of major textbooks. Generic strategies are not specific for site or histology and
      are exclusive of strategies designed for the rare patient, ie, patients who would
      not be considered average in terms of clinical characteristics. Charge data
      obtained from the Part B Medicare Annual Data File and the Hospital Outpatient
      Bill File were used as a proxy for cost. SETTING: Ambulatory care. MAIN OUTCOME
      MEASURES: Nationwide Medicare-allowed charges and an actual-charge proxy for 5
      years of surveillance after treatment for upper aerodigestive tract cancer.
      RESULTS: Medicare-allowed charges for 5-year follow-up ranged from a low of $739
      to a high of $14,079 for the generic and site-specific strategies combined and
      from $739 to $4646 for the 12 generic strategies alone. When Medicare-allowed
      charges were converted to a proxy for actual charges using a conversion ratio of
      1.62, the range was $1198 to $22,807 for all strategies combined (a 19-fold
      difference in charges) and $1198 to $7597 for the generic strategies alone (a 5
      fold difference in charges). CONCLUSIONS: Charges vary extensively across
      surveillance strategies, particularly if site-specific strategies are considered,
      although the potential benefit of more intensive, higher-cost strategies on
      survival or quality of life has yet to be demonstrated.

PMID- 9604985
TI  - Primary malignant lymphoma of the parotid gland.
AB  - OBJECTIVES: To document the clinicopathologic features of primary malignant
      lymphoma of the parotid gland based on analysis of our cases and to compare the
      results with similar studies in the literature. DESIGN: Retrospective,
      nonrandomized case study. SETTING: Academic, tertiary medical center. PATIENTS:
      Forty-one consecutive cases of malignant lymphomas of the parotid gland were
      identified among 820 patients who had undergone parotid surgery during the course
      of 22 years. Thirty-three (80%) of these were primary lymphomas and were included
      in the study. Eight (20%) occurred in patients with a history of malignant
      lymphoma and were therefore excluded. INTERVENTION: Diagnosis was established by
      open parotid biopsy in 8 patients, superficial lobectomy in 23, and total
      parotidectomy in 2. After diagnosis, lymphomas were staged and treated with local
      irradiation and/or chemotherapy. RESULTS: Fifteen men and 18 women aged 26 to 100
      years (mean, 66 years) had an enlarging painless mass on initial examination.
      Seven (21%) had an underlying autoimmune disease and 20 (61%) had Ann Arbor stage
      1 disease at diagnosis. Of 25 patients available for a minimum 2-year follow-up,
      16 (64%) were alive with or without disease. Histological grade was the only
      prognostic feature associated with outcome (P<.01). CONCLUSIONS: Our study, when
      viewed collectively with those in the literature, indicates that malignant
      lymphomas of the parotid gland are uncommon and often not suspected clinically.
      The disease affects both sexes equally and is unusual before the age of 50 years.
      Most are B-cell, non-Hodgkin lymphomas, and about 80% of patients have Ann Arbor
      stage I or II disease at diagnosis.

PMID- 9604986
TI  - Increased mutagen sensitivity in patients with head and neck cancer is less
      pronounced in patients with nasopharyngeal carcinoma.
AB  - BACKGROUND: Mutagen sensitivity tested with bleomycin sulfate can determine a
      susceptible phenotype, which is relevant only in organs and tissues that have
      direct contact with the external environment. Patients with head and neck cancers
      have more mutagen sensitivity than control subjects without cancer, and the
      hypersensitive phenotype has a risk for the development of a second primary
      cancer. Head and neck cancers, however, represent a heterogeneous group of
      neoplasm. The biological behavior of nasopharyngeal carcinoma (NPC) and other
      head and neck cancers differs. OBJECTIVE: To evaluate the difference in mutagen
      sensitivity among patients without cancer, patients with NPC, patients with oral
      or oropharyngeal cancer (ORC), and patients with laryngeal or hypopharyngeal
      cancer (LHC). DESIGN: Peripheral blood was cultured at 37 degrees C, using 5%
      carbon dioxide, for 72 hours. After 67 hours of incubation, bleomycin in a
      concentration of 30 IU/L was added to induce chromatid breaks. The number of
      chromatid breaks per cell was scored in 50 metaphases of cultured lymphocytes and
      compared in the 4 groups. SUBJECTS: Patients with histologically proven squamous
      cell carcinoma of the mucosa of the upper digestive tract, which included 3
      groups: patients with NPC, patients with ORC, and those with LHC. Control
      subjects were hospital inpatients with no tumor history. There were 35 patients
      in each group. RESULTS: The mean (+/-SD) number of breaks per cell in the control
      group and in the groups with NPC, ORC, and LHC were 0.80 (+/-0.32), 1.03 (+/
      0.45), 1.30 (+/-0.44), and 1.35 (+/-0.46), respectively. All the cancer groups
      had significantly higher mean breaks per cell and a higher prevalence of
      hypersensitivity than the control group. Patients with NPC had a significantly
      lower mean number of breaks per cell than the group with ORC or that with LHC.
      CONCLUSIONS: Patients with NPC had less mutagen sensitivity than those with ORC
      or LHC. Our results support the clinical and epidemiological findings of a
      difference between NPC and other head and neck cancers. Environmental factors
      might play a less pronounced role in the carcinogenesis of NPC.

PMID- 9604987
TI  - Regional lymph node metastasis from cutaneous squamous cell carcinoma.
AB  - OBJECTIVE: To characterize clinical presentation and prognostic factors in
      patients with histologically proven regional lymph node metastasis from cutaneous
      squamous cell carcinoma of head and neck origin. DESIGN: Retrospective,
      nonrandomized case series. SETTING: Tertiary referral center. PATIENTS: Forty
      five patients treated between 1984 and 1995 with regional metastatic squamous
      cell carcinoma of cutaneous head and neck origin. INTERVENTION: Forty-one
      patients underwent neck dissection (20 with parotidectomy) and 4 patients
      underwent parotidectomy alone. Thirty-six patients (80%) received postoperative
      radiation therapy with a mean dose of 60 Gy (range, 34-71 Gy). MAIN OUTCOME
      MEASURES: Recurrences and survival by univariate analysis using the Kaplan-Meier
      product-limit method. The log-rank test was used to evaluate prognostic
      significance of clinical variables. RESULTS: Follow-up ranged from 2 months to 10
      years (mean, 21 months). Compared with historical controls, a greater percentage
      of patients in our population with regional lymph node metastasis had primary
      lesions greater than 2 cm in diameter and 4 mm deep. Overall 2- and 5-year
      survival rates were 33% and 22%, respectively, while 5-year disease-free survival
      rate was 34%. Clinical staging of the neck proved to be the only factor of
      prognostic value (P<.01). Treatment failures occurred in 22 patients.
      CONCLUSIONS: For the small subset of patients with regional metastasis from
      cutaneous squamous cell carcinoma, survival remains poor despite multimodality
      treatment. Clinical stage of the neck was the only factor that predicted outcome.

PMID- 9604988
TI  - Eating and weight changes following chemoradiation therapy for advanced head and
      neck cancer.
AB  - OBJECTIVE: To describe the functional outcomes of weight loss and eating
      following a targeted chemoradiation protocol consisting of a selective supradose
      of intra-arterial cisplatin (150 mg/m2 per week for 4 weeks) with parenteral
      sodium thiosulfate and external-beam irradiation (1.8-2.0 Gy per fraction per day
      for 35 days). SUBJECTS AND DESIGN: Forty-seven patients with advanced head and
      neck cancer treated with a targeted chemoradiation protocol were monitored for
      weight and eating status before treatment and as long as 18 months after
      treatment. RESULTS: A statistically significant weight loss (P<.001) occurred
      during the targeted chemoradiation protocol, with a mean weight ratio of 90% of
      the starting weight. The ability to eat also declined, with an increase in
      reported swallowing difficulties and a need for percutaneous endoscopic
      gastrostomy tubes from 4 (9%) to 12 (26%). There were no significant changes in
      weight after the initial weight loss. Tumor stage and nodal involvement had no
      effect on weight loss. At the start of treatment, 18 patients (38%) reported
      normal eating and 4 (8%) required a feeding tube. By 18 months after treatment,
      41 (87%) were eating normally, 34 (72%) reported normal eating, and 6 (13%)
      required a percutaneous endoscopic gastrostomy tube. CONCLUSIONS: Patients
      undergoing a targeted chemoradiation protocol for head and neck cancer lost about
      10% of their pretreatment weight and had a decline in eating ability. Difficulty
      swallowing during the treatment may be due to adverse effects such as mucositis
      and nausea. By 18 months after therapy, most were able to eat normally and
      maintain their weight.

PMID- 9604989
TI  - Laryngeal obstructing saccular cysts: a review of this disease and treatment
      approach emphasizing complete endoscopic carbon dioxide laser excision.
AB  - Airway-obstructing saccular cysts in adults are rare laryngeal anomalies.
      Treatment with tracheotomy may be needed for control of the airway, often
      followed by marsupialization of the cyst wall. Unfortunately, recurrence rates
      are high following marsupialization. We describe 2 patients with saccular cysts
      obstructing the airway and discuss airway management and the results following
      complete endoscopic carbon dioxide laser excision. Both patients had normal voice
      and swallowing function postoperatively and are disease free.

PMID- 9604990
TI  - Radioisotope scanning of the thyroid gland prior to thyroglossal duct cyst
      excision.

PMID- 9604991
TI  - Imaging quiz case 1. Osteoma of the ethmoidal sinus.

PMID- 9604992
TI  - Imaging quiz case 2. Branchial cleft cyst.

PMID- 9604993
TI  - Helper T lymphocyte precursor frequency analysis in alloreactivity detection.
AB  - The utility of IL-2 secreting helper T lymphocyte precursors (HTLp) frequency
      testing has been evaluated for detecting alloreactivity. The frequency of HTLp
      was approached by limiting dilution assay. High HTLp frequency was detected in 20
      out of 30 HLA matched unrelated pairs (67%). The comparison of HTLp and CTLp
      (cytotoxic T lymphocyte precursors) frequencies in HLA matched unrelated pairs
      showed that the two examinations are not fully alternative in detecting
      alloreactivity. This could suggest the utility of combined testing of both HTLp
      and CTLp frequencies for alloreactivity assessment. In contrast, five positive
      HTLp values were only found among 28 HLA genotypic identical siblings (18%).
      Previous CTLp limiting dilution studies showed very low or undetectable CTLp
      frequency results in that group. For that, HTLp assay remains to be the only
      cellular in vitro technique detecting alloreactivity in these combinations.

PMID- 9604994
TI  - The effect of protein kinase C inhibitors on invasion of human ovary cancer
      cells.
AB  - In the present work we tested whether invasiveness of ovarian carcinoma cells
      could be considered as protein kinase C (PKC) dependent process. The migration
      and invasion studies were performed in Transwell chambers. Staurosporine,
      sphingosine and tamoxifen were used as PKC inhibitors. Also the effect of
      prolonged treatment with TPA was the subject of observation. The obtained results
      indicated that invasion understood as three step process (attachment, migration
      and matrix degradation) was affected by PKC inhibitors. The detailed studies,
      however, showed that attachment and matrix degradation ability of ovarian cancer
      cells was not changed by PKC inhibitors as opposed to migration which was, at
      least partly, regulated by protein kinase C.

PMID- 9604995
TI  - The significance of anti-sialyl-Tn antibodies in patients with colorectal and
      breast cancer.
AB  - The sera of 54 individuals with colorectal or breast cancer, and 50 healthy
      volunteers were assayed for the presence of anti-bovine submaxillary mucin
      antibodies using an enzyme linked immunoassay. The serum levels of these
      antibodies were found to be significantly lower in people with breast (p < 0.001)
      or colorectal cancer (p < 0.001) with respect to healthy individuals. Within the
      colorectal cancer group the presence of antibodies was significantly lower in
      those individuals with poorly differentiated tumors compared to other
      histological grades (p < 0.05), but did not correlate with the presence of local
      or distant metastases or anatomical location of the tumor (p > 0.05). No
      correlation was found with respect to the age of the patient and the level of
      anti-sialyl-Tn antibodies (p > 0.05). Competition analysis with the anti-sialyl
      Tn monoclonal antibody 3C2 indicated that the activity against bovine
      submaxillary mucin was primarily due to specificity for the sialyl-Tn epitope of
      the glycoprotein. In contrast to findings with other tumor associated antigens,
      we could find no evidence of an increase in the level of antibodies against this
      epitope.

PMID- 9604996
TI  - Soluble TNF receptors release by polymorphonuclear cells and the serum levels in
      breast cancer patients before and after treatment.
AB  - Soluble cytokine receptors by binding to circulating cytokines play an important
      role in the regulation of immune response of the host. Measurement of their
      release may be helpful in the evaluation of cytokine-mediated reactions in
      patients with cancer disease. Soluble tumor necrosis factor receptors (sTNF-Rs)
      in the culture supernatants of PMNs and in the sera obtained from patients with
      breast cancer were determined. The examinations were carried out before and after
      treatment involving surgery and chemotherapy. The highest concentrations of
      sTNFRp55 and sTNFRp75 were observed in the culture supernatants of PMNs from
      patients before any treatment, the lower concentrations of them were found in the
      supernatants of PMNs after treatment. Sera from breast cancer patients presented
      increased levels of sTNFRp55 and sTNFRp75. Surgery treatment resulted in higher
      concentrations of sTNFRp55 and sTNFRp75. Decreased sTNF-Rs serum levels were
      obtained in patients after adjuvant chemotherapy. Different ability of PMNs to
      the release of TNF-regulatory proteins-sTNFRs appears to confirm PMNs
      participation in TNF-mediated reactions of the host during malignant process via
      sTNF-Rs release.

PMID- 9604997
TI  - The value of CYFRA 21-1, a new tumor marker, in nasopharyngeal carcinoma.
AB  - CYFRA 21-1 (CYFRA) is a newly-developed tumor marker which is useful in
      evaluating non-small cell lung carcinoma, especially the squamous cell type. The
      purpose of this study was to assess the clinical value of CYFRA in patients with
      nasopharyngeal carcinoma (NPC). Serum levels of CYFRA (CIS bio-International,
      France) were measured in 80 patients with untreated NPC. The histologic diagnosis
      of all patients was confirmed by biopsy. Twenty two (27.5%) of the tumors were
      classified as undifferentiated carcinoma, and 58 (72.5%) as squamous cell
      carcinoma. All patients with malignancy were classified according to the
      International Union Against Cancer (UICC) TNM classification system. In addition,
      77 patients without evidence of neoplasm were included as controls. The cut-off
      value of CYFRA, determined at the 95th percentile of the standard Gaussian
      variate of controls, was 2.48 ng/ml. The results show that (1) the mean values of
      serum CYFRA in patients with NPC were significantly higher than those in the
      control subjects, (2) the overall diagnostic sensitivity of CYFRA in patients
      with NPC is 58.75%, (3) there was no significant difference between the CYFRA
      concentrations in patients with squamous cell carcinoma and those in patients
      with undifferentiated carcinoma, and that (4) there was good correlation between
      CYFRA values and the tumor stage. There is a statistical difference between T1-T2
      patients and T3-T4 patients, and between N0 to N1 patients and N2 to N3 patients.
      Our results suggest that the CYFRA test may have a potential clinical role as a
      valuable test in patients with NPC.

PMID- 9604998
TI  - Characterization of two new permanent glioma cell lines 8-MG-BA and 42-MG-BA.
AB  - The establishment and characterization of two permanent glioma cell lines (8-MG
      BA and 42-MG-BA) are described. Both cell lines were derived from the human
      glioblastoma multiforme. Analyzed cells were within the passage 200 to 220. The
      cells in both cultures showed similar morphology. In majority they consisted from
      flat polygonal cells. Growth kinetic studies demonstrated a population doubling
      time of 20 to 24 h in cell line 8-MG-BA and 48 to 54 h in cell line 42-MG-BA. The
      cell lines showed different hyperdiploid karyotypes. The immunofluorescence
      staining was performed for glial fibrillary acidic protein (GFAP) and vimentin.
      In the culture 8-MG-BA only a small amount of cells showed the GFAP-positive
      staining. At confluent 42-MG-BA culture the GFAP-positive cells reached 50 to 70%
      of all cells. Vimentin was found in all glioma cells in both cultures.

PMID- 9604999
TI  - Antitumor action of bovine seminal ribonuclease. Cytostatic effect on human
      melanoma and mouse seminoma.
AB  - This paper reports on the antitumor activity of BS RNase on human melanoma and
      mouse seminoma. Human melanoma cells established in culture were extremely
      susceptible to BS RNase, administered in concentrations ranging from 1-100
      microg/ml. Concentrations of BS RNase over 10 microg/ml caused complete
      inhibition of cell growth. Bovine pancreatic ribonuclease (RNase A), a prototype
      of the ribonuclease superfamily, did not exert any effect under these conditions.
      Based on our previous results, athymic mice bearing human melanoma or mouse
      seminoma were treated with intratumoral administration of BS RNase (12.5 mg/kg
      b.w.). This dose was injected for five consecutive days excluding weekends. The
      intratumoral administration of BS RNase to nude mice bearing human melanoma
      showed a significant antitumor effect. There were no tumors seen in eighty
      percent of mice treated for three weeks, and tumors in the other mice diminished
      significantly. After some delay the tumors started to regrow. Prolonging of the
      treatment to five weeks had a similar effect. The effect of BS RNase on mouse
      seminoma was well pronounced. Five to seven doses of BS RNase were sufficient to
      eliminate tumors in all treated mice. However, as in the previous experiment, the
      growth of tumor tissue later reappeared.

PMID- 9605000
TI  - Granulocyte colony-stimulating factor demonstrates antitumor activity in melanoma
      model in mice.
AB  - Granulocyte colony-stimulating factor (G-CSF) was found to exert antitumor
      activity against murine MmB16 melanoma when administered intratumorally. However,
      subcutaneous administration of this cytokine at a site distant from the growing
      tumor did not show any antitumor effects. G-CSF did not influence the
      proliferative activity of MmB16 in vitro. Intraperitoneal administration of G-CSF
      resulted in decreased secretion of nitric oxide (NO) by peritoneal macrophages
      and their decreased tumoricidal activity against MmB16.

PMID- 9605001
TI  - Signal-averaged ECG in patients after anthracycline therapy for childhood cancer.
AB  - Late cardiac complications after anthracycline therapy is an increasingly common
      problem among survivors of childhood cancer. Routine clinical examination may be
      normal, but subclinical cardiac abnormalities, which may progress with time, are
      documented in high percentage of these patients. Microstructural myocardial
      alterations may result in production of micropotential level signals (late
      potentials, LP) and altered frequency components of signal-averaged ECGs (SAECG).
      SAECG abnormalities are valuable in risk stratification of patients with various
      heart diseases culminating in fatal arrhythmias or heart failure. Forty-five
      pediatric oncologic patients (mean age 14.4 +/- 4.1 years) were included in the
      study. SAECG was performed 3 months-12 years (median 5.5 years) following
      completion of anthracycline therapy. The total cumulative doses of anthracyclines
      were 90-555 (median 230) mg/m2. The control group consisted of 30 healthy age
      matched volunteers. LP were present in six (13.3%) patients after anthracycline
      therapy at 40 Hz high-pass filter setting. Using frequency-domain analysis within
      the QRS complex, area ratio 1 (area of 20 to 50 Hz/area of 0 to 20 Hz) and area
      ratio 2 (area of 40 to 100 Hz/area of 0 to 40 Hz) were calculated. Twenty (44.4%)
      and fourteen (31.1%) had abnormal values in area ratios 1 and 2, respectively,
      within the QRS complex. Area ratios 1 and 2 of patients after anthracycline
      therapy were significantly higher than those in control group (p = 0.0187 and p =
      0.0043). Our preliminary results suggest that chemotherapy with anthracyclines,
      even in low dosage, is associated with increased incidence of SAECG
      abnormalities. The potential of this simple, noninvasive method to detect
      subclinical anthracycline-induced myocardial alterations and facilitate
      prognostic stratification of cancer survivors is promising, however, the clinical
      value of SAECG remains to be established in a larger and a longer study.

PMID- 9605002
TI  - Granisetron in repeated cycles of chemotherapy with platinum.
AB  - The aim of the present study was to assess the antiemetic efficacy of granisetron
      in repeated cycles of chemotherapy with platinum derivatives. The study included
      50 patients (28 females, 22 males; aged 17-72, mean age 51 years). From 2 to 5
      cycles of chemotherapy with cisplatin or carboplatin were performed. Granisetron
      was administered intravenously at a dose of 3 mg, 5 minutes before commencement
      of cytostatic chemotherapy. In case of 2 episodes of vomiting and severe nausea 2
      additional doses of granisetron were given. Total control of emesis was achieved
      in 60% of patients after the first cycle of chemotherapy, and this percentage did
      not change significantly over the 5 cycles of chemotherapy. There were no
      differences in the antiemetic efficacy of granisetron in relation to patient sex
      up to cycle III, while in cycles IV and V a tendency towards less efficacy in
      females was observed. The adverse effects (headache, dizziness) were observed
      with the same frequency in the first 3 cycles of chemotherapy, while these were
      absent in cycles IV and V. Severe side effects were recorded only in cycle I,
      after that they were less expressed. In conclusion, granisetron is highly
      effective in prevention of emesis, induced by platinum derivatives and its
      efficacy is maintained over repeated cycles of chemotherapy. The toxicity of
      granisetron is mostly expressed in the first cycle, while after that it decreases
      significantly.

PMID- 9605003
TI  - The impact of diagnosis and treatment on the quality of life in breast cancer
      patients.
AB  - Over the past years, quality of life (QOL) in patients with breast cancer has
      continued to be a noteworthy area of research. The diagnosis and management of
      cancer can have a major impact on every aspect of a patient's QOL. Sixteen women
      with breast cancer (during chemotherapy and 4 months after adjuvant chemotherapy)
      and 15 healthy women controls underwent 42-item QOL questionnaire in eight
      dimensions which assessed general well-being, physical symptoms and activity,
      sleep disturbance, appetite, sexual dysfunction, cognitive functions, medical
      interaction, social participation, and work performance. The subjects were asked
      to choose only one of five predefined constant options, which were scored from
      one to five in a Likert scale with multiple options, and total QOL scores were
      obtained. Although the total QOL score was not statistically different between
      the groups (p > 0.05), general well-being, physical symptoms and activity, and
      sleep disturbance showed significant regression in breast cancer patients
      compared to the controls (p < 0.05). Appetite (p < 0.02) and physical symptoms
      and activity (p < 0.05) significantly improved in the group after chemotherapy
      compared to the group during chemotherapy.

PMID- 9605004
TI  - Differential display of RNA from tumorigenic and nontumorigenic variants of
      hamster cells transformed with avian sarcoma virus.
AB  - Differential display technique was applied to study expression of RNA in
      tumorigenic and nontumorigenic cell variants of avian sarcoma virus transformed
      hamster cells. Methodical conditions were worked out, which allowed identifying a
      cDNA fragment of an unknown gene expressed in nontumorigenic cell variant only.
      Its role in tumor suppression remains to be determined.

PMID- 9605005
TI  - Treatment of rat gliomas with recombinant retrovirus harboring Herpes simplex
      virus thymidine kinase suicide gene.
AB  - The retrovirus vector containing Herpes simplex virus type 1 thymidine kinase
      (HSVtk) gene was constructed. The vector was transfected into the packaging cell
      line PG13. It was shown that individual transfected cells differ in the
      production of recombinant retrovirus and in their susceptibility to be killed by
      ganciclovir. Recombinant retrovirus with a gibbon envelope was able to transduce
      the HSVtk gene into rat glioma cells. In vivo studies confirmed the ability of
      intraperitoneal ganciclovir administration to influence subcutaneous and
      intracerebral tumors developed after injection of C6 rat glioma cells with
      subsequent injection of HSVtk retrovirus producing cells.

PMID- 9605006
TI  - Quantitative immunocytofluorometry--new parameters for the definition of leukemia
      cells.
AB  - In our study we used for definition of leukemia/lymphoma cells a new parameter
      which allows the enumeration of mean fluorescence intensity expressed by the
      number of antigen molecules per cell. Quantitative immunofluorescence using
      calibration microbeads was performed in 36 patients with different acute and
      chronic lymphoid and myeloid leukemia and in 19 healthy volunteers. We showed
      that quantitative immunophenotyping allowed the definition of aberrant marker
      densities on neoplastic cells. We demonstrated under- and overexpression of CD8
      marker in CD3/CD4/CD8 complex in T acute lymphatic leukemia and T non-Hodgkin's
      lymphoma and T leukemia of large granular lymphocytes as compared to normal
      counterparts. We pointed out that certain antigens (e. g. CD10, CD4, CD24) were
      expressed at different levels on different cell subsets (CD10 in early B-acute
      lymphatic leukemia and coexpressed in T-acute lymphatic leukemia, CD4 on T cells
      and monocytes, CD24 on B cells and granulocytes in chronic myeloid leukemia). We
      showed that quantitative immune fluorescence could provide new data contributing
      to a more precise definition of cell differentiation. We documented the
      significant difference between antigen density of early and late markers in B
      cell and myeloid malignancies. Further, we demonstrated that quantitative immune
      phenotyping could help in determination of exact definition of pathologic clone
      in morphologically immature leukemia population and showed that parameters of
      this method are also convenient for cytoplasmic marker evaluation. In our study
      we were able to demonstrate that CD45 quantitative expression appeared to be a
      more informative parameter than its percentage of antigen-positive cells as a
      measure of antigen expression only and we pointed out that low and high CD45
      densities enabled to differentiate between pathological clone and residual
      healthy population in examined sample. We showed that quantitative immune
      phenotyping could be another important parameter for definition of leukemia
      phenotype suitable for detection of minimal residual disease.

PMID- 9605007
TI  - The relationship between argyrophilic proteins and some immunophenotypic markers
      in acute leukemia cells.
AB  - This study reports the immunophenotypic features of a series of 62 selected acute
      leukemia patients with increased incidence of argyrophilic proteins (AgNORs) at
      the time of initial diagnosis. Peripheral blood and bone marrow cells of patients
      with T-ALL, B-precursor ALL and AML were studied. The method of silver staining
      was used to determine the number of AgNORs per cell. Cell surface markers were
      detected by a standard immunofluorescence assay. To demonstrate the relationship
      between AgNOR quantity and cell proliferation, the expression of activation and
      proliferation antigens CD38 and CD71 was investigated. To characterize the
      immunophenotype and the discrete stages of differentiation, the wide panel of
      antibodies against lymphoid, myeloid and non-lineage specific antigens was used.
      The number of AgNORs at diagnosis ranged from 3.05 to 6.70. Immunophenotypic
      analysis showed a variation in CD38 and CD71 expression among different leukemia
      subtypes. CD71 antigen was more expressed in T-ALL than in B-precursor ALL or in
      AML. Notable was the relationship between increased AgNOR quantity and antigens
      that characterize the immaturity of leukemic cells. The association with CD7,
      CD2, CD5 (without CD3 membrane expression) and CD34 in T blasts was evident. High
      positivity of CD19, CD10, CD34 and HLA-DR in relation to the increased amount of
      AgNORs in B-lineage ALL was observed. The vast majority of AML patients with high
      numbers of AgNORs simultaneously expressed CD13, CD33, CD34 and HLA-DR. One third
      of AML cases coexpressed T cell marker CD7. In conclusion, the presence of
      increased numbers of AgNORs at diagnosis might reflect the dependence on an early
      stage of leukemia cell differentiation.

PMID- 9605008
TI  - Inhibitory effect of radiosensitizer AK-2123 on experimental hepatic metastases
      and Ca2+ active transport.
AB  - A triazole group radiosensitizer AK-2123 is shown to inhibit considerably the
      growth of hepatic metastases induced by the intrasplenic injection of colon
      adenocarcinoma cells in syngenic mice. Even an extremely low dose of the drug
      exhibits the antimetastatic effect. It is shown that AK-2123 injected at
      therapeutic dose inhibits active transport of calcium ions by the (Ca2+-Mg2+)
      dependent ATP-ase. The antimetastatic effect of AK-2123 is suggested to be
      related, at least partially, to the inhibition of the active calcium transport.

PMID- 9605009
TI  - Human multidrug-resistant (MRP,p190) myeloid leukemia HL-60/ADR cells in vitro:
      resistance to the mevalonate pathway inhibitor lovastatin.
AB  - Mevalonate pathway inhibitor lovastatin inhibited proliferation of human
      multidrug-resistant promyelocytic leukemia HL-60/ADR cells in vitro, with MRP
      gene coded p190 mediated drug resistance, to a markedly lesser extent than that
      of the parental drug sensitive HL-60 cells and also that of the other human
      multidrug resistant (MDR-1, P-glycoprotein) myeloid leukemia cell line HL-60/VCR.
      The sensitivity of the examined human leukemia cell lines to the cytostatic
      activity of lovastatin correlated approximately with the potential of lovastatin
      to induce the characteristic cell cycle alteration (i.e. the accumulation of
      lovastatin-treated cells in the G0/G1 phase of the cell cycle). The P
      glycoprotein positive HL-60/VCR cells and the parental drug sensitive HL-60 cells
      were more sensitive to this cell cycle alteration than the HL-60/ADR multidrug
      resistant leukemia cells with MRP drug resistance. Lovastatin (72 hours, 20
      micromol) induced apoptosis and cell necrosis in HL-60 cells, apoptosis but not
      cell necrosis in HL-60/VCR cells and neither apoptosis nor necrosis in HL-60/ADR
      cells.

PMID- 9605010
TI  - The intermediate filaments and prognostically oriented morphological
      classification in ductal breast carcinoma.
AB  - The expression of cytokeratins 7, 8, 14, 18, 19 and vimentin was examined in 100
      cases of ductal invasive breast carcinomas. While the predominantly diffuse
      immunohistological positivity of simple epithelia cytokeratins 7 (in 93), 8 (in
      100), 18 (in 100) and 19 (in 97) cases represents a constant feature of these
      tumors, cytokeratin 14 was detected in only 36 cases which were mostly of low
      grade and in a focal pattern. Vimentin positivity was found in 53 intermediate
      and high grade tumors and, again the pattern was also rarely diffuse. The ductal
      carcinomas can be grouped into four classes according to vimentin and cytokeratin
      14 immunoreactivity. This grouping correlates well with tumor grade and with
      simple histological classification of ductal breast carcinoma, consisting of the
      low, intermediate and high malignancy categories, as proposed here. The types
      ofductal carcinomas can be sorted into prognostically different subgroups,
      according to ICD-O morphologic terminology and commonly adopted results of
      morphologic and prognostic studies.

PMID- 9605011
TI  - Searching for a functional analogy between yeast Pso4 and bacterial RecA proteins
      in induced mitotic recombination.
AB  - The pso4-1 mutant of S. cerevisiae is phenotypically similar to the recA mutant
      of E. coli; it is sensitive to DNA cross-linking agents and defective in both
      recombination and mutagenesis. In this paper we have measured the effect of the
      recA gene expression on the frequency of mitotic crossing-over and mitotic gene
      conversion in response to DNA damage induced by photoactivated 8-methoxypsoralen
      (8-MOP + UVA), ultraviolet radiation (UV) and N-methyl-N'-nitro-N
      nitrosoguanidine (MNNG). The diploid pso4-1 mutant and the repair wild type
      strain were transformed with the multicopy plasmid carrying the recA gene placed
      under the control of the ADH1 promoter. The results showed that RecA is not able
      to restore block in induced mitotic recombination in pso4-1 cells after DNA
      damaging agents used. Thus RecA protein is not able to substitute Pso4 protein in
      homologous mitotic recombination indicating that they have probably different
      functions in this process.

PMID- 9605012
TI  - Measurement of DNA strand breakage and DNA repair induced with hydrogen peroxide
      using single cell gel electrophoresis, alkaline DNA unwinding and alkaline
      elution of DNA.
AB  - Three techniques: single cell gel electrophoresis (SCGE), alkaline elution of DNA
      (AE), and alkaline DNA unwinding (ADU) were chosen to compare the sensitivity
      among these methods in detection of DNA damage and repair in human diploid VH10
      cell line after short-term exposure to hydrogen peroxide. Using SCGE technique a
      dose-dependent increase in DNA migration was found in cells exposed to hydrogen
      peroxide in concentration range from 10 micromol/l to 100 micromol/l. Alkaline
      DNA unwinding method detected increased level of single strand breaks (ssb) in
      concentration range from 25 micromol/l to 100 micromol/l of H2O2, and alkaline
      elution of DNA estimated increased DNA elution rate from concentration 50
      micromol/l of H2O2. In a time course study to evaluate the kinetics of DNA
      repair, both SCGE and ADU techniques showed that the repair of DNA strand breaks
      is very rapid; the level of ssb in treated cells has returned to near the
      background level within two hours. After this time damage remaining in the DNA
      was in the form of oxidised bases as revealed the incubation of treated cells
      with specific DNA repair endonuclease, formamidopyrimidine-DNA glycosylase.

PMID- 9605013
TI  - Polarographic testing of carcinogenicity of some chemotherapeutics.
AB  - This work is devoted to the study of polarographic reduction of three antibiotic
      compounds including adriamycin, chloramphenicol and erythromycin and of a
      synthetic antibacterial chemotherapeutic compound--5-nitrofurantoin. The
      polarographic reduction was performed in the strictly anhydrous N,N
      dimethylformamide with or without alpha-lipoic acid (LA) by the means of DC
      polarography. The values of half-wave potentials E1/2 and parameter of potential
      carcinogenicity were determined for the all compounds. Adriamycin was reduced
      during the five-step process, other compounds were reduced in two steps. The
      presence of LA in a polarographic solution resulted in a new polarographic one
      electron wave in the range of -1.120 V to -1.790 V vs. SCE possessing a diffuse
      and reversible character. Its height is linearly dependent on the LA
      concentration in solution. The highest parameter of potential carcinogenicity tg
      alpha was determined for adriamycin (0.575) which belongs among compounds
      classified by WHO as "probably carcinogenic to humans". The lowest determined
      value of parameter tg alpha belonged to 5-nitrofurantoin (0.290) which has not
      yet been included into the IARC classification.

PMID- 9605014
TI  - Plasma selenium concentration in patients with stomach and colon cancer in the
      Upper Silesia.
AB  - Plasma selenium concentration was assessed in 44 patients with cancer of the
      gastrointestinal tract (19 subjects with stomach cancer and 25 with colon cancer)
      and 25 age-matched healthy control subjects. Selenium concentration was
      determined by the fluorometric method. The observed plasma selenium
      concentrations in gastrointestinal cancer patients (37.0 +/- 11.05 ng Se/ml or
      38.4 +/- 12.6 ng Se/ml in stomach or colon cancer patients, respectively) were
      significantly lower as compared to the healthy age-matched control group (51.4 +/
      14.4 ng Se/ml). The diagnosed low selenium status may be considered as a high
      risk for cancer development.

PMID- 9605015
TI  - Mechanisms and prevention of pneumonia in the elderly.
AB  - Pneumonia is not only a major cause of death for elderly persons, but also
      imposes substantial personal morbidity and burdens on the health care system. An
      understanding of the pathogenesis of this serious illness could allow us to
      devise methods for curbing the incidence and severity of the disease.
      Pathophysiological issues and preventative measures are the subject of this
      review.

PMID- 9605016
TI  - Frequency of chromosome 7 gain in human breast cancer cells: correlation with the
      number of metastatic lymph nodes and prognosis.
AB  - Trisomy 7 has been reported in various malignant neoplasms, but there are no
      reports in breast cancer. In order to evaluate the contribution of chromosome 7
      gain to breast cancer, we investigated the relationship of numerical abberation
      of chromosome 7 with clinicopathological variables and prognosis in seventy-nine
      breast cancer cases (invasive carcinomas) using the technique of fluorescence in
      situ hybridization (FISH) on paraffin-embedded sections. A significant
      correlation of the frequency of cells with extra copies of chromosome 7 (percent
      polysomy 7 cell score) was found with tumor size, regional lymph node status, tnm
      stage, histological extension, estrogen receptor (ER), and DNA ploidy. The number
      of metastatic lymph nodes was positively correlated with percent polysomy 7 cell
      score (correlation coefficient=0.623, p < 0.01). Furthermore, cases with a high
      percent polysomy 7 cell score had a shorter disease-free survival and overall
      survival times, especially in the lymph node-positive group. It was demonstrated
      that percent polysomy 7 cell value was closely associated with lymph node
      metastasis and prognosis and might be a useful prognostic predictor of breast
      cancer patients.

PMID- 9605017
TI  - Immunohistochemical analysis of matrix proteolytic enzymes in the periprosthetic
      tissue in the patients with loosening prostheses.
AB  - Regional periprosthetic bone resorption plays an important role of prosthesis
      loosening. In order to study the possible mechanisms of loosening, we
      investigated the presence of matrix proteolytic enzymes in the periprosthetic
      tissue by immunohistochemical technique in 72 patients undergoing revision
      operation of loosened joint prosthesis, including 22 males and 50 females and
      aged from 19 to 88 years (mean, 61.7 years). Thirty-nine patients had a loosened
      hip prosthesis (18 males and 21 females) whereas 33 patients had a loosened knee
      prosthesis (4 males and 29 females). Tissue specimens collected during revision
      surgery underwent thin slide sections and H & E staining, and were observed under
      light microscopy and polarized-light microscopy. The results showed many
      macrophages, histiocytes, fibroblasts, as well as many phagocytosed metal debris
      and polyethylene debris in the periprosthetic tissues, suggesting an active bone
      resorption. Furthermore, we used immunohistochemical techniques to detect the
      distribution of matrix proteolytic enzymes in periprosthetic tissue, including
      lysosome enzymes (cathepsin B, cathepsin D and cathepsin G), and matrix
      metalloproteinase (MMPs, MMP-1, MMP-2, MMP-3). The immunostaining were classified
      as strong positivity, > 70% positive cells; moderate positivity, 20-70% positive
      cells; weak/negative, < 20% positive cells. The results showed that cathepsin B,
      cathepsin D and cathepsin G were found in most fibroblasts and macrophage-like
      cells, including multinuclear giant cells and epithelioid cells. MMPs were found
      in most fibroblasts and macrophage-like cells, as well as a scant amount in the
      extracellular matrix. These enzymes were also found in or around blood vessels,
      the endothelial cells in the richly vascularized tissue. All negative controls
      showed no staining. The results of immunoreactive staining ranged from 61.1% to
      68.1% of strong to moderate positivity. Since these enzymes were related to the
      degradation of matrix protein, they may be related to the periprosthetic bone
      resorption. The further clinical significance needs further investigation.

PMID- 9605018
TI  - Growth hormone improves mouse embryo development in vitro, and the effect is
      neutralized by growth hormone receptor antibody.
AB  - We investigated whether growth hormone(GH) may influence the development of mouse
      embryo in vitro using recombinant GH and anti-growth hormone receptor(GHR)
      antibody. When mouse two-cell-stage embryos were cultured with GH, 5, 10 mIU/ml,
      the rates of formation of both blastocysts and of hatched blastocysts from two
      cell-stage embryos were significantly higher than in the medium without GH. The
      number of blastomeres from blastocyst treated with GH, 2, 5 and 10 mIU/ml, was
      significantly higher than those cultured without GH. When cultured blastocysts
      were implanted in recipient uteri, a significantly higher implantation rate was
      found for the GH-treated(10 mIU/ml) mouse embryos than for controls. To confirm
      the GH effect, anti-GHR monoclonal antibody MAb5 was employed to neutralize the
      action of GH through GHR. Two-cell-stage mouse embryos were cultured with GH, 10
      mIU/ml, and anti-GHR antibody, and as a control, embryos were cultured with GH
      alone. Both the rate of formation of blastocysts from two-cell-stage embryos and
      the number of blastomeres were significantly decreased in groups exposed to anti
      GHR antibody. Results indicate that GH may be important to early embryonic
      development, acting through GHR. GH may help to obtain good quality embryos and
      improve the implantation rate in IVF programs.

PMID- 9605019
TI  - Detection of Mycobacterium tuberculosis in preserved tuberculous lymph nodes by
      polymerase chain reaction.
AB  - We evaluated the usefulness of three types of polymerase chain reaction (PCR)
      targeting 16S rRNA, protein antigen b and IS6110 in detecting Mycobacterium
      tuberculosis in preserved tuberculous lymph nodes. The detection limit of all PCR
      methods was 100 colony forming unit (CFU) of M. tuberculosis in tissue. The test
      samples included eight paraffin-embedded tuberculous lymph nodes containing
      microscopical epithelioid cell granuloma with caseous necrosis and Langhans giant
      cells. Although acid-fast stained organisms in lymph node tissue were not
      detected in any sample, all three types of PCR tests were positive in four of
      eight lymph nodes. Our results suggest that PCR is not only a rapid and sensitive
      diagnostic method for tuberculous lymphadenitis, but also clinically significant
      in retrospective study for detecting M. tuberculosis even in some preserved lymph
      node tissues without evidence of acid-fast stained organisms.

PMID- 9605020
TI  - Relation between histological intensity of transforming growth factor-beta
      isoforms in human osteosarcoma and the rate of lung metastasis.
AB  - Even though adjuvant chemotherapy has improved the 5-year survival rate of
      osteosarcoma patients, a significant percentage of patients eventually die from
      lung metastasis. Since transforming growth faCtor-beta (TGF-beta) has been
      demonstrated to be related to the tumor progression, we investigated the clinical
      implications of the presence of TGF-beta isoforms in 16 human osteosarcoma
      tissue. There were 10 males and 6 females with a mean age of 20.8 years of age
      (range, 8 to 57 years). Biopsied specimen before chemotherapy was fixed in 10%
      formalin, demineralized and followed by paraffin embedding. The locations of
      tumor included femur (10), tibia (3), humerus (1), fibula (1), and ilium (1).
      Histologic subtypes included osteoblastic (11), chondroblastic (2), and
      fibroblastic (3). All patients were followed for a minimum of 1 year (range 12 to
      44 months) or to the development of lung metastasis. Five patients (31.3%)
      developed subsequent lung metastasis during the follow up. We used
      immunohistochemistry technique to investigate the presence of the TGF-beta
      isoforms in osteosarcoma tissue and its relationship to the subsequent pulmonary
      metastasis. The results showed the presence of one or more TGF-beta isoforms in
      tumor cells in osteosarcoma tissues (13 of 16, 81.3%) in all of the subtypes.
      However, minimal presence of TGF-beta isoforms was shown in the tumor bone
      matrix. The expression of TGF-beta1 or TGF-beta3 isoforms was associated with a
      higher rate of subsequent lung metastasis (p < 0.05, chi-square test). Further
      research is warranted to determine the utility of routine TGF-beta analysis in
      the clinical practice.

PMID- 9605021
TI  - Fertilization potential and qualitative characteristics of human spermatozoa
      after short-term cryostorage at 5 degrees C in two different TEST-yolk buffer
      preparations.
AB  - Use of the media TEST-yolk buffer (TYB) in semenology today enables the short
      term incubation and cryostorage of spermatozoa and its subsequent use in the
      various assisted reproductive technologies (ART). Preparation of TYB media
      involves the addition of egg yolk (20% v/v) to a physiological solution of the
      zwitterion buffers TES and Tris. The TYB is usually thermoprecipitated to remove
      the majority of the egg yolk globules and other macromolecules from the medium.
      However, removal of these egg yolk constituents could possibly eliminate or
      reduce essential factors that could enhance the sperm viability and fertilization
      potential after short-term dilution and storage. Improvements in the quality of
      the TYB could add greater benefits to those techniques employed in the various
      forms of ART. The objectives of the investigation were 1) to study the sperm
      qualitative characteristics following short-term cryostorage at 5 degrees C in
      either thermoprecipitated (T-TYB) or non-thermoprecipitated (NT-TYB), and 2) to
      compare the fertilizing potential of spermatozoa stored for 24 hours at 5 degrees
      C in the two TYB preparations. In Experiment 1, semen specimens from 15 patients
      were collected, assessed and split into two aliquots. Sperm specimens were
      processed by diluting 1:1 (v/v) with the T-TYB or NT-TYB, followed by
      centrifugation and reconstitution of the specimen to its initial volume with the
      corresponding TYB medium. Sperm specimens were cryostored for 1, 2, 24, 48 and 72
      hours. Samples were taken at each interval and placed in a 37 degrees C water
      bath and allowed to warm for 15 minutes after each cryostorage interval. Semen
      specimens were assessed for percentage and grade of motility. The results of this
      study indicated that, although the NT-TYB yielded better results than the T-TYB,
      overall those differences were not statistically significant. In Experiment 2,
      the fertilization potential of spermatozoa recovered after 24 hours of
      cryostorage in the two TYB preparations and further prepared via filtration, was
      assessed by the sperm penetration assay (SPA) using zona-free hamster oocytes.
      The average penetration rate (PR) and penetration index (PI) were significantly
      better for the NT-TYB than for the T-TYB. The PR was 54% vs. 25%, and the PI 0.78
      and 0.27 for spermatozoa incubated in the NT-TYB vs. T-TYB. The range of
      penetration was also much lower for the T-TYB (6 to 100%) preparation when
      compared to the NT-TYB (22 to 100%). The highest penetrator showed 100% for both
      preparations. However, the lowest penetrator showed 6% for the T-TYB and 22% for
      the NT-TYB. The data obtained in this study suggest that both TYB preparations
      can be employed in short-term cryostorage (5 degrees C) of human spermatozoa and
      can adequately maintain the qualitative characteristics of those spermatozoa. The
      data also showed that the NT-TYB preparation yielded sperm samples of higher
      fertilization potential, thus possibly establishing the superior usefulness of
      the NT-TYB in an ART program.

PMID- 9605022
TI  - Effect of rolling bed on decubitus in bedridden nursing home patients.
AB  - Decubitus is one of the most difficult management problems encountered in
      bedridden elderly patients. Relief of pressure over decubitus is the most
      important principle of the management. We developed a rolling air cushion bed
      which turns the patient to a 15-degree inclined lateral position with an
      inflating ripple mattress, a longitudinally aligned air inflatable tube. The
      position of the patients was changed between right and left laterals and to
      supine every 15 minutes automatically. Nineteen bedridden patients with decubitus
      used the rolling air cushion bed for 3 months and 12 bedridden patients with
      decubitus used a conventional bed and had their position changes every 2 hours by
      care givers. Severity of decubitus was divided into 4 grades and the decubitus
      significantly improved from 2.8 (S.E. 0.2) to 2.0 (S.E. 0.3) after 3 months in
      patients using the rolling air cushion bed, while in patients with conventional
      beds it changed from 3.0 (S.E. 0.2) to 3.2 (S.E. 0.2) (not statistically
      significant). We suggest that the rolling air cushion bed would be beneficial to
      decubitus relief in bedridden elderly and may relieve labor by care givers.

PMID- 9605023
TI  - The painful reality of hunger.

PMID- 9605025
TI  - Efficacy of peripherally inserted central venous catheters placed in noncentral
      veins.
AB  - BACKGROUND: Peripherally inserted central venous catheters (PICCs) are commonly
      used intravenous access devices in children. Although PICCs are intended to be
      placed in central veins, many fail to reach this location. These noncentral PICCs
      are used for administration of medications and isotonic solutions. OBJECTIVES: To
      examine the efficacy of noncentral PICCs for completion of therapy, the
      complications associated with their use, and the effectiveness of noncentral
      PICCs as compared with PICCs placed in a central vein. DESIGN: A prospective
      cohort study of children in whom PICCs were inserted, from January 1, 1994, to
      January 1, 1996. SETTING: A university-affiliated teaching institution. MAIN
      OUTCOME MEASUREMENT: Completion of intravenous therapy. RESULTS: A total of 587
      PICCs were studied. Thirty-nine percent of PICCs were placed in noncentral veins.
      Centrally placed PICCs had significantly longer catheter duration compared with
      those placed noncentrally (16.6 vs 11.4 days, respectively). However, central and
      noncentral PICCs had similar therapy completion rates (73% and 69%,
      respectively). Catheter failure because of occlusion and accidental dislodgment
      were similar for central and noncentral PICCs. Likewise, complications caused by
      exit-site infection, phlebitis, and catheter-associated sepsis were also similar
      for catheters in the 2 locations. Catheter survival curves were similar for
      central and noncentral PICCs. CONCLUSIONS: Our study demonstrates that PICCs
      placed in noncentral veins provide reliable and safe intravenous access for
      administration of many medications and isotonic solutions for about 2 weeks'
      duration. The placement of PICCs in central veins may be restricted to those
      children who need central vascular access because of the type of intended
      therapy.

PMID- 9605024
TI  - A quantitative review of mortality and developmental disability in extremely
      premature newborns.
AB  - OBJECTIVES: To summarize the literature on mortality rates and prevalences of
      major neurodevelopmental disabilities and to examine trends of these outcomes
      over time in extremely premature neonates. DATA SOURCES: MEDLINE was used to
      search the English literature for studies published since 1970 reporting on both
      mortality and disability in infants born at or before 26 weeks' gestation
      (extremely immature [EI] cohort), with a birth weight of 800 g or less (extremely
      small [ES] cohort), or subgroups of these. STUDY SELECTION: Studies were included
      in the analysis if all of the following were reported: mortality; direct
      examination of 75% or more of the survivors; and the proportion of patients with
      at least 1 of the following disabilities: cerebral palsy, mental retardation,
      blindness, and deafness. Studies reporting cohorts included as a subset of
      cohorts in another study were excluded. Forty-two studies providing mortality and
      disability data for 20 cohorts of 4116 EI infants and 38 cohorts of 4345 ES
      infants born after 1972 met the inclusion criteria. DATA EXTRACTION: Data were
      abstracted from all studies that met these criteria by two of us (J.M.L. and
      D.E.W.), independently; the data were then cross-checked to ensure accuracy.
      RESULTS: Survival averaged 41% for EI infants and 30% for ES infants, and it
      increased significantly with time. In contrast to mortality, the prevalences of
      major neurodevelopmental disabilities among survivors have not changed over time.
      The most common major disability was mental retardation, found in 14% of EI and
      ES survivors. Cerebral palsy was found in 12% of EI survivors and 8% of ES
      survivors, blindness was found in 8% of EI and ES survivors, and deafness was
      found in 3% of EI and ES survivors. Overall, 22% of EI survivors and 24% of ES
      survivors were classified as having at least 1 major disability. Each 100 EI or
      ES livebirths yielded 7 children with major disabilities; this prevalence was
      correlated with survival across cohorts. CONCLUSIONS: The prevalence of
      disabilities had not changed among EI or ES survivors with increasing survival.
      However, increasing survival of these infants has resulted in a steadily
      increasing prevalence of children with disabilities.

PMID- 9605026
TI  - Families' recommendations for improving services for children with chronic
      conditions.
AB  - BACKGROUND: Little research has been done on services and programs for children
      with chronic conditions and their families from the perspective of family
      caregivers from diverse cultural backgrounds. OBJECTIVE: To identify
      recommendations that urban caregiving families from 3 major ethnocultural
      backgrounds have for improving the care of children with chronic conditions (ie,
      chronic illnesses and disabilities involving physical health impairments).
      DESIGN: Qualitative, community-based study. SETTING: General community.
      PARTICIPANTS: The volunteer convenience sample included 21 African American, 20
      Hispanic, and 22 European American families from 2 midwestern cities who care for
      school-aged children with chronic conditions. METHODS: In-home semistructured
      interviews were conducted with each child's family caregivers. Content analytic
      techniques were used to identify and classify 275 recommendations from 63
      families. RESULTS: Families focused on the following 4 topics: (1) improving the
      quality of health care services; (2) decreasing barriers to services and
      programs; (3) improving the training that health care professionals, families,
      and the public receive about chronic conditions and their management; and (4)
      improving the quality and availability of community-based services. Families from
      all 3 ethnic groups had similar recommendations for improving services and
      programs; however, several African American and Hispanic families also suggested
      making information more culturally relevant and resources more accessible to
      families from diverse cultural backgrounds. CONCLUSIONS: The findings indicate
      that further work needs to be done to deliver care that is, indeed, family
      centered and culturally sensitive. Families' recommendations provide information
      that health care professionals and policymakers can use to transform rhetoric
      about family-centered care into action.

PMID- 9605027
TI  - Adolescent girls and pelvic inflammatory disease: experience and practices of
      emergency department pediatricians.
AB  - OBJECTIVE: To describe the experience and practices of emergency department
      pediatricians in the United States related to the diagnosis and management of
      pelvic inflammatory disease (PID) in adolescent girls and to compare this
      experience with Centers for Disease Control and Prevention recommended management
      guidelines. DESIGN: National telephone survey. SUBJECTS: One hundred four
      pediatricians randomly selected from the 659 members of the Section on Emergency
      Medicine of the American Academy of Pediatrics. Response rate was 56%. MEASURES:
      A 42-item structured interview questionnaire assessed physician demographics,
      practice characteristics, PID diagnosis and management, and attitudes about
      sexually transmitted diseases in adolescents. RESULTS: Fifty-one (94%) of 54
      emergency department pediatricians had diagnosed PID in adolescents at least once
      within the past 2 years, and 35 (69%) had diagnosed PID, on average, once per
      month or more. Less than half the pediatricians (23/51 [45%]) routinely
      recommended hospital admission for adolescents with PID as suggested by the
      Centers for Disease Control and Prevention, and among those treating adolescents
      with PID as outpatients,just over half (20/37 [54%]) arranged close follow-up
      within 72 hours of initiating antibiotic treatment. Although most emergency
      department pediatricians routinely suggested condom use (47/54 [87%]) and human
      immunodeficiency virus testing (34/54 [63%]) after diagnosing a sexually
      transmitted disease, a minority routinely provided contraceptive counseling
      (23/54 [43%]) or written partner notification (17/54 [31%]). Approximately two
      thirds of pediatricians surveyed indicated that they thought that the care of an
      adolescent with a sexually transmitted disease should be different from that of
      an adult (35/54 [65%]) and that this age group was more prone to medical
      complications (38/54 [70%]). CONCLUSIONS: The results of this survey suggest that
      emergency department pediatricians frequently diagnose PID in adolescent girls
      and understand the high risk of medical complications in this age group, but
      their management is often less aggressive than that recommended by Centers for
      Disease Control and Prevention guidelines and sexually transmitted disease
      experts.

PMID- 9605028
TI  - A community outreach lead screening program using capillary blood collected on
      filter paper.
AB  - OBJECTIVE: To test whether a method of fingerstick blood sample collection onto
      filter paper could be used as an alternative screening method in the field in
      settings where environmental lead contamination is a high risk. METHOD: Members
      of the Pediatric Mobile Team of Children's Hospital of Michigan, Detroit,
      collected paired venous and capillary blood samples from 120 children, aged 6
      months to 6 years, who presented for services at any of 7 sites located in
      decaying neighborhoods of older sections of Detroit. All samples were analyzed
      for lead content by graphite furnace atomic absorption spectrometry. RESULTS:
      When filter paper samples with blood lead levels of 0.48 micromol/L (10
      microg/dL) or higher were compared with matched venous samples, the concordance
      coefficient was 0.96. The sensitivity and specificity of the filter paper samples
      relative to the venous samples for a cutoff of 0.48 micromol/L (10 microg/dL) or
      higher were 94% and 99%, respectively, with a positive predictive value of 97%.
      However, at a cutoff of 0.72 micromol/L (15 microg/dL), the sensitivity and
      specificity dropped to 75% and 98%, respectively, with filter paper samples
      underreporting blood lead values. At any cutoff point (0.48, 0.72, or 0.96
      micromol/L [10, 15, or 20 microg/dL]), the filter paper method was highly
      specific for lead. CONCLUSIONS: Capillary filter paper sampling is an accurate
      and practical alternative to venous sampling for blood lead screening using 0.48
      micromol/L (10 microg/dL) as the cutoff. The filter paper method predicts levels
      of 0.72 micromol/L (15 microg/dL) or higher less well. The cause of divergent
      values above 0.72 micromol/L (15 microg/dL) is not clear. Environmental
      contamination of capillary filter paper, however, does not seem to be an
      explanation.

PMID- 9605029
TI  - Evaluation of a clinic-based program to promote book sharing and bedtime routines
      among low-income urban families with young children.
AB  - OBJECTIVE: To evaluate a program of anticipatory guidance in which pediatric
      residents and nurse practitioners in a continuity practice gave parents books for
      their young children along with developmentally appropriate educational materials
      describing why and how to share the books and promoting reading as part of a
      bedtime routine. STUDY DESIGN: Comparison of 2 cross-sectional groups using
      consecutive, structured, face-to-face or telephone interviews of parents. One
      group was a historical control or a comparison group (group 1). The other was the
      intervention group (group 2), which included families who had received 2 books
      and educational materials for the children as part of the program to promote book
      sharing and bedtime routines. SUBJECTS: Before the institution of the program to
      promote book sharing and bedtime routines, the parents in 51 families with
      healthy children 12 to 38 months of age who regularly attended continuity clinics
      conducted by the house staff were interviewed; these families constituted group
      1. Group 1 included a low-income population of Hispanic, African American, and
      non-Hispanic white families. Group 2 included 100 families with similar
      sociodemographic characteristics with healthy 12- to 38-month-old children who
      had received 2 books and educational materials at all 6- to 36-month well-child
      visits as part of the program. RESULTS: The intervention was found to be
      effective in promoting child-centered literacy activities. When asked openended
      questions, 4 (8%) of the parents in group 1 and 21 (21%) of the parents in group
      2 said 1 of their child's 3 favorite activities included books (P=.04); 11 (22%)
      of the parents in group 1 and 42 (42%) of the parents in group 2 said 1 of their
      3 favorite activities with their child was book sharing (P=.01); and 10 (20%) of
      the parents in group 1 and 35 (35%) of the parents in group 2 said that they
      share books 6 or 7 times a week at bedtime (P =.05). By mentioning 1 of these 3
      important child-centered book-sharing activities, 17 (33%) of the parents in
      group 1 and 69 (69%) of the parents in group 2 (P <.001) demonstrated positive
      child-centered literacy orientation . A multiple logistic regression analysis
      controlling for parental education, ethnicity, and reading habits, as well as for
      the sex and age of the children, found child-centered literacy orientation more
      likely to be present in group 2 than in group 1 families, with an odds ratio (OR)
      of 4.7 (95% confidence interval [CI], 2.1-10.5; P<.001). Book sharing as part of
      a bedtime routine was more frequent in group 2 (mean+/-SD, 3.9+/-2.6 nights per
      week) than in group 1 (mean+/-SD, 2.5+/-2.7 nights per week; P=.002); however, no
      significant differences in prolonged bedtime struggles, parent-child co-sleeping,
      frequent night waking, or how children fell asleep were found between the groups.
      Instead, in multivariate analysis, bedtime struggles occurred more often with
      younger parents (P=.03) and fewer children at home (P=.02), while parent-child co
      sleeping (P<.001) and frequent night waking (P=.04) were less likely to occur
      when children usually fell asleep alone in their own beds. CONCLUSIONS: This
      simple and inexpensive intervention by pediatric house staff, consisting of the
      provision of children's books and educational materials at well-child visits,
      resulted in increased enjoyment of and participation in child-centered book
      related activities in low-income families. Primary care providers (ie, physicians
      and nurse practitioners) serving underserved pediatric populations may have a
      unique opportunity to promote child-centered literacy in at-risk groups.

PMID- 9605030
TI  - Sun protection by families at the beach.
AB  - BACKGROUND: During the last decade, results of surveys of adults showed an
      increase in sun protection knowledge, a slight decline in the attitude that
      having a tan was healthy, widespread sunscreen use as the principal method of
      solar protection, and an increase in sunburning. METHODS: During the summer of
      1996, observers recorded the sun protection activities of 352 family groups as
      they arrived at the beach and did concurrent interviews. RESULTS: Ninety-eight
      percent of families using sunscreen applied it after arrival at the beach and it
      was the dominant form of sun protection used. Usually, the adult woman provided
      the sunscreen and applied it to a child before applying it to herself. The median
      delay in application from arrival at the beach to application to the last family
      member was 51 minutes. Wearing either a hat, shirt, or sunscreen by 1 adult was
      associated with wearing the same item by at least 1 child in the family group
      (hat, P<.001; shirt, P<.001; sunscreen, P<.001). Children's sunscreen use was
      associated with having fair skin and a parent who used it. CONCLUSIONS: Because
      those with fair skin type are more likely to use sunscreen and to burn after
      short periods of exposure, delay in sunscreen application may cause sunburns.
      While solar protection has become part of routine beach behaviors for most
      families, there is room for improvement with better application of sunscreen;
      more use of clothing, especially hats; and seeking shade.

PMID- 9605031
TI  - Development of a research child growth reference and its comparison with the
      current international growth reference.
AB  - OBJECTIVE: To better characterize childhood growth and further assess potential
      limitations of the current National Center for Health Statistics and World Health
      Organization international growth reference. DESIGN: The LMS method was used for
      curve fitting to summarize the changes in height and weight distributions by 3
      curves representing the skewness (L), median (M), and coefficient of variation
      (S). A series of polynomial regression procedures was applied to smooth the L, M,
      and S curves. SETTING: Subset data from 18 states contributing clinic data to the
      Centers for Disease Control and Prevention Pediatric Nutrition Surveillance
      System were used for this research reference. METHODS: We chose only those
      clinics in which the height and weight distributions of children closely matched
      with those of the first and second National Health and Nutrition Examination
      Surveys. RESULTS: Unlike the current international growth reference, the new
      reference has no disjunction at 24 months of age because it is based on a single
      data source for children aged 0 to 59 months. The reference also better
      characterizes the growth for infants than the current international reference, a
      fact we demonstrated with data from the National Health and Nutrition Examination
      Surveys, Pediatric Nutrition Surveillance System 1995, and the Davis Area
      Research on Lactation, Infant Nutrition, and Growth studies. CONCLUSIONS: The
      current National Center for Health Statistics and World Health Organization
      international growth reference needs to be updated. The methods used in this
      study will be useful to evaluate other data sets and to evaluate future
      modifications of growth references.

PMID- 9605032
TI  - Deletion 22q11: a newly recognized cause of behavioral and psychiatric disorders.
AB  - BACKGROUND: Chromosome 22q11 deletion (del22q11), the most common microdeletion
      syndrome, causes a wide spectrum of clinical disorders. Recent studies have
      suggested that significant psychiatric and behavioral disturbances occur in up to
      60% of these individuals. OBJECTIVE: To illustrate the spectrum of behavioral and
      psychiatric abnormalities associated with del22q11 and the subtle nature of its
      associated physical findings. PATIENTS AND METHODS: Case series describing
      psychiatric and behavioral findings in 3 patients with del22q11. RESULTS AND
      CONCLUSIONS: Behavioral and psychiatric problems are common in patients with
      del22q11 syndrome. Because the physical manifestations of the disorder are so
      variable and may be subtle, the behavioral and psychiatric manifestations may be
      the presenting problem. Providers must therefore consider del22q11 as a potential
      diagnosis in children and adults with behavioral and psychiatric problems.
      Furthermore, behavioral and psychiatric problems need to be looked for when
      caring for children and adolescents with a known diagnosis of del22q11.

PMID- 9605033
TI  - Management of lead poisoning from ingested fishing sinkers.
AB  - OBJECTIVE: To describe what is to our knowledge the first reported case of lead
      poisoning from ingested fishing sinkers in an 8-year-old boy for whom whole bowel
      irrigation and colonoscopy were required. LITERATURE REVIEW: All relevant
      literature on plumbism from other swallowed foreign bodies, including curtain
      weights, bullets, shot, and other unusual sources, is reviewed and discussed.
      CONCLUSIONS: Lead screening is advocated in any child presenting with a history
      of pica or foreign-body ingestion, especially presentations involving abdominal
      pain, weight loss, and emesis. Conservative management of retained foreign bodies
      containing lead is not recommended with persistently high lead levels. Medical
      and surgical intervention should be considered.

PMID- 9605034
TI  - Hunger in midwestern inner-city young children.
AB  - OBJECTIVE: To determine the characteristics of hunger in young children who
      attend ambulatory pediatric clinics in a midwestern city. DESIGN: Consecutive
      sample. SETTING: Ambulatory pediatric clinics of an inner-city teaching hospital.
      PARTICIPANTS: English-speaking caregivers of 2578 children younger than 5 years.
      MAIN OUTCOME MEASURE: Structured survey measures of hunger, family
      characteristics, assistance program use, child feeding practices, and
      anthropometrics. RESULTS: In this population, 171 (6.6%) were hungry, and 842
      (32.7%) were at risk for hunger. Hunger status was associated with increased age
      (P<.001), decreased maternal education level (P=.013), maternal nonwhite race
      (P<.002), a history of homelessness (P<.001), and parental unemployment (P<.001).
      Hunger status was associated with use of Aid to Families with Dependent Children
      (P<.001) and food stamps (P<.001) but not with participation in The Special
      Supplemental Nutrition Program for Women, Infants, and Children (WIC). Results of
      anthropometrics indicated that mean growth percentiles were no different between
      hunger categories. CONCLUSIONS: Housing, dietary, and family characteristics are
      identifiable risk factors for early childhood hunger. Hunger cannot be
      identified, however, using anthropometrics. It is disconcerting that fewer hungry
      children and children at risk for hunger participate in WIC compared with other
      programs. These data suggest the potential for more aggressive identification and
      intervention at the primary care and social service levels to benefit hungry
      children.

PMID- 9605035
TI  - Pediatric residents: are they ready to use computer-aided instruction?
AB  - OBJECTIVE: To assess pediatric residents' readiness to use computer-aided
      instruction (CAI). DESIGN: Survey. SETTING: Pediatric residency program based in
      a tertiary care children's hospital. PARTICIPANTS: Four pediatric residency
      classes. ASSESSMENT INSTRUMENT: Self-administered questionnaire. MAIN OUTCOME
      MEASURES: Residents' access to computers and the Internet, experience with CD-ROM
      and World Wide Web computer tutorials, and attitudes toward CAI. Responses were
      stratified by age, training level, sex, and previous computer education. RESULTS:
      Fifty-one (69%) of the residents owned a computer. Men were more likely than
      women to own a computer (20 [87%] of 23 men vs 31 [61%] of 51 women; P=.02).
      Medical education software was used by 18 (28%) of 65, but only 2 (4%) of 74 had
      ever purchased CAI. Twenty-seven (36%) of 74 regularly accessed medical education
      World Wide Web sites. Nineteen (26%) of 74 had never accessed the Internet. Of
      those who had, 50 (91%) of 55 continued to do so at least weekly. Eighteen (95%)
      of the 19 residents who had never accessed the Internet were female (P=.005). Men
      were twice as likely to have Internet access at home (P=.01) and were more likely
      to regularly visit medical education World Wide Web sites (P=.02). Attitudes
      toward CAI were positive. Most respondents would be willing to use CAI developed
      at their institution. Most residents ranked CAI ahead of printed teaching
      materials but behind personal teaching by a pediatrician. Attitudes did not
      differ by sex. CONCLUSION: Despite positive attitudes toward CAI, pediatric
      residents are not yet universally ready to use CAI.

PMID- 9605036
TI  - Radiological case of the month. Torsed ovary with a dermoid cyst.

PMID- 9605037
TI  - Picture of the month. Hand-foot-and-mouth disease.

PMID- 9605038
TI  - Pathological case of the month. Chromosome 10 qter deletion syndrome.

PMID- 9605039
TI  - Pathological case of the month. Primary hepatic malignant tumor with rhabdoid
      features.

PMID- 9605040
TI  - Aluminum toxicity.

PMID- 9605041
TI  - Vinyl miniblinds and childhood lead poisoning.

PMID- 9605042
TI  - Growth in tobacco promotion overstated.

PMID- 9605043
TI  - One-year outcomes of diabetic versus nondiabetic patients with non-Q-wave acute
      myocardial infarction treated with percutaneous transluminal coronary
      angioplasty.
AB  - Risk factors and outcomes associated with non-Q-wave myocardial infarction (MI)
      in diabetics and nondiabetics were analyzed for 376 consecutive patients, 77 with
      diabetes (20%) and 299 nondiabetics (80%), who had non-Q-wave MI and had
      percutaneous transluminal coronary angioplasty (PTCA) performed before discharge
      from hospital during the period from January 1992 to February 1996. Diabetics
      were slightly older (64 +/- 10 years vs 61 +/- 12 years, p <0.053), had more
      prior coronary artery bypass grafting (CABG) surgery (27% vs 12%, p <0.001), and
      hypertension (77% vs 49%, p <0.001). There was no significant difference in
      unstable angina, saphenous vein graft PTCA, single versus multiple vessel
      disease, or history of MI. PTCA success rates for diabetics versus nondiabetics
      were similar (96% vs 97%, p = NS). In-hospital complications such CABG, recurrent
      MI, repeat PTCA, stroke, and death were not statistically significant between the
      2 groups. At 1-year follow-up, survival in diabetics (92%) was similar to
      nondiabetics (94%, p = NS), although event-free survival (PTCA, CABG, MI, death)
      was worse in diabetics (55% vs 67% for nondiabetics, p <0.05). Although diabetic
      patients with non-Q-wave MI represent a cohort with more risk factors for poor
      outcome, aggressive in-hospital revascularization with PTCA results in an
      excellent short-term outcome as well as 1-year survival similar to the
      nondiabetic patients. However, total events at 1-year follow-up are more common
      in the diabetic patients, suggesting that more aggressive screening and therapy
      in follow-up may be warranted, and that a diabetic with non-Q-wave MI will
      require increased utilization of cardiovascular resources in the first year after
      the event.

PMID- 9605044
TI  - Predictive value of planar 18F-fluorodeoxyglucose imaging for cardiac events in
      patients after acute myocardial infarction.
AB  - This long-term study examines the predictive value of planar myocardial 18F
      fluorodeoxyglucose (FDG) imaging for cardiac events after acute myocardial
      infarction (AMI). From December 1989 to April 1991, 59 consecutive patients with
      AMI had undergone planar rest thallium-201 (Tl-201)/FDG imaging for viability
      assessment; 53 (42 men) were included in this study. Mean follow-up was 47 +/- 15
      months. Cardiac events were defined as cardiac-related death, reinfarction, late
      revascularization, and unstable angina pectoris. A mismatch pattern was defined
      as a FDG uptake exceeding Tl-201 uptake by > or = 20%. A concordant reduction in
      flow and metabolism was defined as a match. In the mismatch group (n = 39) were
      19 events versus 1 event in the match group (n = 14) (p <0.009). In the mismatch
      group were 5 cardiac deaths, 3 reinfarctions, 7 late revascularizations, and 4
      patients had unstable angina pectoris. There was 1 cardiac death in the match
      group. The event-free rate estimated using Kaplan Meier curves for patients with
      and without a mismatch was significantly different (p = 0.018). The relative risk
      for patients with a mismatch for developing a future cardiac event was estimated
      at 7.8 versus patients with a match. Thus, planar myocardial FDG imaging shortly
      after AMI has important prognostic significance for prediction of future cardiac
      events. Patients with a mismatch shortly after AMI have a high risk for future
      cardiac events on medical therapy.

PMID- 9605045
TI  - Higher T-wave amplitude associated with better prognosis in patients receiving
      thrombolytic therapy for acute myocardial infarction (a GUSTO-I substudy). Global
      Utilization of Streptokinase and Tissue plasminogen Activator for Occluded
      Coronary Arteries.
AB  - Increased T-wave amplitude is one of the earliest electrocardiographic (ECG)
      changes following coronary artery occlusion. Therefore, higher T waves in the
      presenting electrocardiogram should represent earlier time to treatment and thus
      be associated with lower mortality following thrombolytic therapy. However, T
      wave amplitude has never been evaluated as a prognostic marker in this setting.
      We examined clinical outcomes in 3,317 patients with acute myocardial infarction
      (AMI) who underwent thrombolysis in the Global Utilization of Streptokinase and t
      PA for Occluded Coronary Arteries (GUSTO-I) Study. Patients were classified as
      either those with high T waves or those with low T waves. Higher T waves were
      defined as those >98th percentile of the upper limit of normal. T-wave amplitude
      was also evaluated as a continuous variable according to infarct location
      (maximum T-wave amplitude) and as the amount of excess T-wave amplitude above
      normal (excess T-wave amplitude). Patients with higher T waves had lower 30-day
      mortality than those without (5.2% vs 8.6%, p = 0.001) and were less likely to
      develop congestive heart failure (15% vs 24%, p <0.001) or cardiogenic shock
      (6.1% vs 8.6%, p = 0.023). Higher maximum T-wave amplitude and excess T-wave
      amplitude were predictive of lower 30-day mortality (chi-square = 67, p <0.001
      and chi-square = 33, p <0.001, respectively). These differences remain
      significant after controlling for other prognostic baseline ECG variables. In
      addition, T-wave amplitude added prognostic significance after controlling for
      time to treatment. T-wave amplitude, an often-overlooked component of the
      electrocardiogram, can add significant prognostic information in initial
      evaluation of patients with AMI.

PMID- 9605046
TI  - Effects of verapamil on indexes of heart rate variability after acute myocardial
      infarction.
AB  - In patients with previous myocardial infarction (MI), depressed heart rate
      variability (HRV) may reflect a reduction in vagal activity and lead to cardiac
      electrical instability. Interventions designed to increase HRV may be of clinical
      interest. Data on the effects of calcium antagonists on HRV in post-MI patients
      are very limited. The aim of our study was to assess the effects of verapamil on
      HRV and on the sympathovagal balance after MI. Fifty consecutive patients with a
      first MI, stable sinus rhythm, and left ventricular ejection fraction >0.40 were
      studied. Each patient underwent two 24-hour Holter recordings, 1 at baseline and
      another after 4 days of treatment with verapamil retard (180 mg 2 times daily).
      Time and frequency domain parameters of HRV were analyzed. All time domain
      measurements increased significantly after verapamil: the standard deviation of
      all NN intervals (SDNN) from 87.1 +/- 31.4 to 98.1 +/- 30.3 ms (p <0.05) and the
      log-transformed percentage of pairs of adjacent NN intervals that differ >50 ms
      (pNN50) from 0.57 +/- 0.42 to 0.76 +/- 0.45 (p <0.01). The standard deviation of
      the averages of RR interevals (SDANN) (75.9 +/- 30.1 vs 86.3 +/- 29.4 ms, p
      <0.05), root-mean-square of successive differences between RR intervals (rMSSD)
      (23.0 +/- 11.7 and 28.1 +/- 13.1 ms, p <0.01), and the triangular HRV index (28.3
      +/- 9.6 vs 23.4 +/- 8.6, p <0.001) also increased. A significant inverse
      correlation was found between improvement in HRV indexes induced by verapamil and
      baseline values. Spectral analysis showed a significant increase in high
      frequency power of 58.5% without changes in low and very low components. With
      normalized units, significant reductions in low-frequency power and low- to high
      frequency ratio were observed. Diabetic patients did not show any significant
      changes in HRV on administration of verapamil. These findings indicate that
      verapamil, administered during the subacute phase of MI, improves both global and
      short-period indexes of HRV and induces a shift in the sympathetic
      parasympathetic interaction toward vagal predominance. This effect may contribute
      to an explanation of the beneficial effects of verapamil that have been reported
      in post-MI patients.

PMID- 9605047
TI  - Pericardial effusion after primary percutaneous transluminal coronary angioplasty
      in first Q-wave acute myocardial infarction.
AB  - To evaluate the incidence and clinical significance of infarction-associated
      pericardial effusion in patients with successful primary percutaneous
      transluminal coronary angioplasty, we studied 214 consecutive patients with a
      first Q-wave acute myocardial infarction. Based on 9 clinical variables,
      multivariate analysis was performed to determine the important variables related
      to the occurrence of pericardial effusion. Pericardial effusion was detected by
      echocardiography in 45 patients (21%); pericardial rub (p <0.001), number of
      advanced asynergic segments (p <0.001), ventricular aneurysmal motion (p = 0.03),
      and pulmonary capillary wedge pressure (p = 0.04) were found to be the important
      variables related to pericardial effusion. Among 45 patients with pericardial
      effusion, 29 patients with no pericardial rub had significantly higher pulmonary
      capillary wedge pressure than those with pericardial rub, whereas 16 patients
      with pericardial rub had a higher incidence of angiographic no reflow and
      ventricular aneurysmal motion than those without pericardial rub. Patients with
      pericardial effusion and a pericardial rub had a higher mortality rate than those
      without pericardial effusion (19% vs 3%; p = 0.02). Thus, pericardial effusion is
      still a relatively common clinical finding after primary percutaneous
      transluminal coronary angioplasty, and those with pericardial effusion and a
      pericardial rub were associated with more severe transmural myocardial damage and
      higher in-hospital mortality.

PMID- 9605048
TI  - A comparison of percutaneous transluminal coronary angioplasty in the Department
      of Veterans Affairs and in the private sector in the State of Washington.
AB  - Coronary angioplasty is performed > 1,000 times daily in a variety of health care
      settings in the public and private sectors in the USA. How outcomes for this
      procedure differ in the Department of Veterans Affairs and the private sector is
      unknown. The purpose of this study was to compare outcomes of coronary
      angioplasty performed in hospitals in the Department of Veterans Affairs and the
      State of Washington. This study used administrative data from the Department of
      Veterans Affairs patient treatment file (n = 8,326) and the State of Washington
      episode of illness file (n = 6,666) and included men who underwent coronary
      angioplasty in 1993 and 1994. Outcomes included (1) in-hospital mortality and
      mortality at 10 and 30 days after hospital admission, and (2) the use of coronary
      artery bypass surgery at similar intervals. Patients with a principal diagnosis
      of acute myocardial infarction were analyzed separately. Men in the Department of
      Veterans Affairs had more comorbid conditions than their counterparts in
      Washington State, and the length of hospital stay was longer in the former group.
      After using logistic regression to adjust for patient differences, mortality
      rates for the 2 groups of patients with acute myocardial infarction were similar,
      although bypass surgery was used more frequently in patients in Washington State.
      For patients without myocardial infarction, hospital and 10-day mortality did not
      differ with respect to health care system, and the use of bypass surgery
      subsequent to angioplasty was similar. In the Department of Veterans Affairs,
      most hospitals had low institutional caseloads (< 150 procedures per year),
      whereas > 40% of Washington State hospitals performed > or = 300 procedures per
      year. Although there were greatly differing institutional caseloads, mortality
      and the need for early bypass surgery were similar in the 2 systems.

PMID- 9605049
TI  - A new criterion combining ST/HR slope and deltaST/deltaHR index for detection of
      coronary artery disease in patients on digoxin therapy.
AB  - We evaluated the clinical value of a new index combining deltaST/delta heart rate
      (HR) index and ST/HR slope for diagnosing coronary artery disease (CAD) in
      patients on digoxin therapy. Exercise treadmill tests were performed by 72
      patients on digoxin therapy. Simple HR-adjusted indexes of ST-segment depression
      during exercise (deltaST/deltaHR index) and the decline calculated from the final
      12 data points relating ST-segment depression to HR (ST/HR slope) were
      determined. A new index was obtained by subtracting the deltaST/deltaHR index
      from the ST/HR slope. On thallium scintigraphy, 37 of the 72 patients showed
      reversible perfusion defects related to the diseased coronary artery. The new
      index derived from this ST-HR relation was 4.1 +/- 3.6 microV/beats/min in the
      ischemic group and 1.3 +/- 1.0 microV/beats/min in the group of patients without
      ischemia (p <0.0001). An ST-HR relation > or = 1.5 was found in 33 of the 37
      patients in the ischemic group, and in 7 of the 35 patients without ischemia (p
      <0.0001). The sensitivity of this criterion for prediction of myocardial ischemia
      was 89%, the specificity was 80%, and the predictive accuracy was 85%. Thus, this
      new ST-HR index is useful for detecting CAD in patients on digoxin therapy.

PMID- 9605050
TI  - Coronary vascular remodeling in association with endothelial dysfunction.
AB  - Vascular remodeling has been demonstrated in advanced and early coronary artery
      disease. Whereas the endothelium may play a role in the adaptive process of
      vascular remodeling, it is not known if this process occurs in association with
      changes in coronary blood flow reserve. Early coronary atherosclerosis is
      characterized by endothelial dysfunction which is manifested by an abnormal
      coronary blood flow in response to the endothelium-dependent vasodilator
      acetylcholine. This study was designed to test the hypothesis that coronary
      vascular remodeling occurs in association with coronary endothelial dysfunction
      early in the development of coronary atherosclerosis. Thirty-six patients found
      to have normal coronary angiograms or mild coronary artery disease were studied.
      Acetylcholine was infused into the left anterior descending artery. Patients were
      divided into 2 groups based on their coronary blood flow response to
      acetylcholine. Intravascular ultrasound measurements of the proximal left
      anterior descending diameter and area were obtained. Vessel diameter and area
      were measured at the external elastic membrane and indexed to body surface area.
      Vessel diameter and area were greater in patients with abnormal than normal
      responses to acetylcholine (5.2 +/- 0.3 mm and 19.5 +/- 0.9 mm2 vs 3.9 +/- 0.3 mm
      and 12.3 +/- 1.0 mm2; p <0.02, respectively). This difference persisted when
      measurements were indexed to body surface area. The current study suggests in
      vivo in humans that coronary vascular remodeling characterized by enlargement of
      the proximal coronary arteries occurs in association with endothelial dysfunction
      early in the course of coronary artery disease.

PMID- 9605051
TI  - Direct medical costs of coronary artery disease in the United States.
AB  - To generate current incidence-based estimates of the direct medical costs of
      coronary artery disease (CAD) in the United States, a Markov model of the
      economic costs of CAD-related medical care was developed. Risks of initial and
      subsequent CAD events (sudden CAD death, fatal/nonfatal acute myocardial
      infarction [AMI], unstable angina, and stable angina) were estimated using new
      Framingham Heart Study risk equations and population risk profiles derived from
      national survey data. Costs were assumed to be those related to treatment of
      initial and subsequent CAD events ("event-related") and follow-up care ("nonevent
      related"), respectively. Cost estimates were derived primarily from national
      public-use databases. First-year direct medical costs of treating CAD events are
      estimated to be $17,532 for fatal AMI, $15,540 for nonfatal AMI, $2,569 for
      stable angina, $12,058 for unstable angina, and $713 for sudden CAD death.
      Nonevent-related direct costs of CAD treatment are estimated to be $1,051
      annually. The annual incidence of CAD in the United States is estimated at
      616,900 cases, with first-year costs of treatment totaling $5.54 billion. Five-
      and 10-year cumulative costs in 1995 dollars for patients who are initially free
      of CAD are estimated at $9.2 billion and $16.5 billion, respectively; for all
      patients with CAD, these costs are estimated to be $71.5 billion and $126.6
      billion, respectively. The direct medical costs of CAD create a large economic
      burden for the United States health-care system.

PMID- 9605052
TI  - A predictive instrument for coronary artery aneurysms in Kawasaki disease. US
      Multicenter Kawasaki Disease Study Group.
AB  - To construct a predictive instrument for developing coronary artery abnormalities
      in patients with acute Kawasaki disease treated with aspirin and intravenous
      gamma globulin within the first 10 days of illness, data available from a
      multicenter database of patients with acute Kawasaki disease were analyzed. A
      development data set (n = 212) was used to construct a sequential risk
      classification instrument based on easily measured baseline laboratory test
      results and temperature. The instrument was then validated in 3 test data sets (n
      = 192, 264, and 92, respectively). Risk factors used in the sequential
      classification instrument included baseline neutrophil and band counts,
      hemoglobin concentration, platelet count, and temperature on the day after
      infusion of intravenous gamma globulin. In the development data set, the
      instrument classified 123 of 212 patients (58%) as low risk; none developed
      coronary artery abnormalities. Among 89 patients classified as high risk, 3 of 36
      female (8.3%) and 9 of 53 male patients (17.0%) developed coronary artery
      abnormalities. The instrument performed similarly in the 3 test data sets; no
      patient in any data set classified as low risk developed coronary artery
      abnormalities. This simple instrument allows the clinician to identify within 1
      day of treatment low-risk children in whom extensive and frequent cardiac testing
      may be unnecessary, as well as high-risk children who require closer monitoring
      and may be candidates for additional therapies.

PMID- 9605053
TI  - Safety of oral propafenone in the treatment of arrhythmias in infants and
      children (European retrospective multicenter study). Working Group on Pediatric
      Arrhythmias and Electrophysiology of the Association of European Pediatric
      Cardiologists.
AB  - This study was designed to assess adverse effects of oral propafenone in a large
      number of pediatric patients. Retrospective data from 27 European centers
      covering 772 patients treated with oral propafenone were analyzed. The following
      arrhythmias were treated: reentrant supraventricular tachycardia in 388 patients,
      atrial ectopic tachycardia in 66, junctional ectopic tachycardia in 39, atrial
      flutter in 21, ventricular premature complexes in 140, ventricular tachycardia in
      78, and other arrhythmias in 39 patients. Two hundred forty-nine patients (32.3%)
      had structural heart disease. Significant electrophysiologic side effects and
      proarrhythmia were found in 15 of 772 patients (1.9%): sinus node dysfunction in
      4, complete atrioventricular block in 2, aggravation of supraventricular
      tachycardia in 2, acceleration of ventricular rate during atrial flutter in 1,
      ventricular proarrhythmia in 5, and unexplained syncope in 1 patient. Cardiac
      arrest or sudden death occurred in 5 of 772 patients (0.6%): 2 patients had
      supraventricular tachycardia due to the Wolff-Parkinson-White syndrome and a
      normal heart; the remaining 3 patients had structural heart disease. Overall,
      adverse cardiac events were more common in the presence (12 of 249 patients,
      4.8%) than in the absence (8 of 523 patients, 1.5%) of structural heart disease
      (p <0.01). There was no difference between patients treated for supraventricular
      and ventricular arrhythmias. Thus, propafenone is a relatively safe drug for the
      treatment of several pediatric tachyarrhythmias. Proarrhythmic effects seem to be
      less frequent than those reported for encainide or flecainide and occur
      predominantly in patients with structural heart disease.

PMID- 9605054
TI  - Mechanical dysfunction of the left atrium and the left atrial appendage following
      cardioversion of atrial fibrillation and its relation to total electrical energy
      used for cardioversion.
AB  - In 39 patients undergoing electrical cardioversion for atrial fibrillation (AF),
      we examined the effect of total electrical energy used for cardioversion on
      postcardioversion peak left atrial (LA) rapid filling velocity (A) and the atrial
      emptying fraction, and recovery of LA effective mechanical atrial function
      (defined as peak A velocity > or = 0.50 m/s), as assessed by transthoracic
      echocardiography. In a subset of 27 patients who underwent pre- and
      postcardioversion transesophageal echocardiography, we assessed the relation
      between total electrical energy and LA appendage filling and emptying velocities
      and spontaneous echo contrast. Patients were randomized to receive an initial
      shock of 1.5 J/kg based on body weight, or 2.5, 3.5, 5 J/kg, or 360 J, followed
      sequentially by higher shock intensities until sinus rhythm was achieved.
      Patients were classified into 4 groups based on quartiles of total energy
      delivered for cardioversion. Conversion to sinus rhythm was associated with a
      significant decrease in the LA appendage filling velocities (0.42 +/- 0.20 m/s vs
      0.29 +/- 0.14 m/s; p = 0.002) and LA appendage emptying velocities (0.40 +/- 0.22
      m/s vs 0.29 +/- 0.18 m/s; p = 0.03), but no change in the incidence of
      spontaneous echo contrast (61% vs 70%, p = 0.08). The 4 groups of patients did
      not differ with respect to postcardioversion LA appendage filling velocities, LA
      appendage emptying velocities, incidence of spontaneous echo contrast, or
      worsening of spontaneous echo contrast. Similarly, the change in LA appendage
      filling and emptying velocities associated with cardioversion was not different
      between the groups. Furthermore, postcardioversion peak A velocity and atrial
      emptying fraction and recovery of effective mechanical atrial function were
      similar between the 4 groups. These results suggest that in patients undergoing
      electrical cardioversion for AF, the total electrical energy used for
      cardioversion has no effect on the mechanical function of the left atrium or LA
      appendage following cardioversion.

PMID- 9605055
TI  - Loss of adrenergic control of the force-frequency relation in heart failure
      secondary to idiopathic or ischemic cardiomyopathy.
AB  - This study was designed to determine whether the force-frequency effect on
      myocardial contractility, known to be importantly regulated by the adrenergic
      nervous system in experimental animals, can be enhanced by beta-adrenergic
      receptor stimulation in patients with heart failure. Animal experiments have
      demonstrated that the positive force-frequency relation in most mammals is
      subject to enhancement by beta-adrenergic receptor stimulation during exercise or
      infusion of a beta-receptor agonist. In animal models of heart failure, this
      regulatory mechanism generally is lost. The response to progressive increases in
      heart rate to 150 to 160 beats/min by right atrial pacing before and during
      dobutamine infusion was studied in 3 relatively normal subjects and in 5 patients
      with severe dilated cardiomyopathy. Left ventricular (LV) pressure and its first
      derivative (LV dP/dt(max)) were measured with a micromanometer, and the time
      constant of LV relaxation was assessed. The slopes of the relations between heart
      rate and LV dP/dt(max) in control subjects were positive at baseline and the mean
      slope increased substantially and significantly during dobutamine infusion. In
      patients with heart failure, the heart rate versus LV dP/dt(max) relations were
      depressed and flattened without a descending limb. Dobutamine infusion shifted
      this relation upward slightly, without increase in mean slope, indicating lack of
      amplification. The rate of isovolumic relaxation significantly decreased as heart
      rate increased at baseline and was further shortened by dobutamine. In patients
      with heart failure, a depressed and flattened relation between heart rate and LV
      dP/dt(max) (force-frequency effect) did not show the amplification of myocardial
      contractility by beta-adrenergic stimulation observed in the normal heart. This
      abnormality in control of the force-frequency relation undoubtedly plays an
      important role in the impairment of cardiac function during exercise in heart
      failure.

PMID- 9605056
TI  - Left atrial mechanical adaptation to long-standing hemodynamic loads based on
      pressure-volume relations.
AB  - Left atrial (LA) adaptation during the development of left ventricular (LV)
      dysfunction is not fully understood. We performed echocardiographic assessment of
      LA volumes simultaneously with recordings of pulmonary wedge pressures in 60
      patients. Twenty patients had no structural or functional LV abnormalities, 20
      had a recent myocardial infarction with LV dysfunction, and 20 suffered from
      congestive heart failure (CHF). Pressure-volume loops were obtained at baseline
      and during increases in LA pressure produced by normal saline infusion. LA
      afterload was estimated by the effective LV elastance (E(LV)). Atrioventricular
      coupling was calculated by the E(LV)/E(es) ratio (where E(es) is the end-systolic
      elastance). E(es) increased in patients with myocardial infarction (0.80 +/- 0.09
      mm Hg/ml, p <0.001), whereas it decreased in patients with CHF (0.22 +/- 0.05 mm
      Hg/ml, p <0.001) compared with controls (0.61 +/- 0.07 mm Hg/ml). Similarly,
      stroke workload increased in patients with myocardial infarction (60.7 +/- 7.3 mm
      Hg x ml, p <0.001), whereas it decreased in patients with CHF (25.4 +/- 2.2 mm Hg
      x ml, p <0.001) compared with controls (44.8 +/- 5.5 mm Hg x ml). In all patients
      LA stiffness (slope of the relation of the filling portion of the pressure-volume
      loop) was increased compared with controls (controls: 0.13 +/- 0.04, patients
      with myocardial infarction: 0.22 +/- 0.05, and patients with CHF: 0.27 +/- 0.05
      mm Hg/ml, p <0.001 for both comparisons). Moreover, the E(LV)/E(es) ratio
      increased gradually as LV function deteriorated (controls: 1.06 +/- 0.10,
      patients with myocardial infarction: 1.35 +/- 0.16, and patients with CHF: 6.90
      +/- 0.84, p <0.001). Thus, early in heart failure, LA pump function is augmented
      but LA stiffness increases and work mismatch occurs. With further progression of
      LV dysfunction, LA pump function decreases as a result of increased afterload
      imposed on the LA myocardium.

PMID- 9605057
TI  - Usefulness of transesophageal echocardiography in predicting mortality and
      morbidity in stroke patients without clinically known cardiac sources of embolus.
AB  - This study tested the hypothesis that stroke patients without a cardiac source of
      embolism suspected by clinical examination can be risk stratified by
      transesophageal echocardiography. Forty ischemic stroke patients without atrial
      fibrillation, prosthetic valves, ejection fraction < 20%, or recent myocardial
      infarction underwent multiplane transesophageal echocardiography: 24 (designated
      high risk) had > or = 1 of the following: left heart thrombus, vegetation, mass
      or spontaneous echo contrast, mobile ascending aortic or arch debris, patent
      foramen ovale, atrial septal defect or aneurysm, mitral annular calcification,
      mitral valve thickening, prolapse or mitral valve strands. End points were death,
      recurrent stroke, transient ischemic attack, myocardial infarction or peripheral
      embolism. Thirty-eight patients (95%) (23 high, 15 low risk) were followed for 14
      +/- 8 months: 9 (24%) died of vascular causes including 4 who had a cardiac cause
      of death and 5 who had fatal strokes. Eight had recurrent strokes (4 nonfatal)
      and 1 nonfatal myocardial infarction occurred. Cardiovascular survival was
      predicted by transesophageal echocardiography: survival rates were 92% (low risk)
      and 63% (high risk) at 24 months (p = 0.036). Left atrial enlargement was
      independently associated with death from stroke (fatal stroke occurred in 25% of
      those with atrial enlargement compared to 8% of those with normal atrial
      dimension, p < or = 0.03), as was left atrial spontaneous echo contrast (50% died
      vs 9% without contrast, p < or = 0.03). Left ventricular hypertrophy and aortic
      atherosclerosis were both associated with the risk of recurrent stroke (30% of
      patients with ventricular hypertrophy had recurrent stroke compared to 10% with
      normal wall thickness (p < or = 0.05); 30% with aortic atherosclerosis had a
      recurrent stroke compared to none with a normal aorta (p < or = 0.05). Thus,
      transesophageal echocardiography clearly identifies patients at a high risk for
      cardiovascular mortality and morbidity after stroke despite an unsuspected source
      of embolism by clinical examination.

PMID- 9605058
TI  - Cardiac output responses during exercise in volume-expanded heart transplant
      recipients.
AB  - The mechanisms responsible for immediate adjustments in cardiac output at onset
      of exercise, in the absence of neural drive, are not well defined in heart
      transplant (HT) recipients. Seven male HT recipients (mean +/- SD 57 +/- 6 years)
      and 7 age-matched sedentary normal control subjects (mean age 57 +/- 5 years)
      performed constant load cycle exercise at 40% of peak power output (Watts).
      Cardiac output and plasma norepinephrine were determined at rest and every 30
      seconds during the first 5 minutes of exercise and at minutes 6, 8, and 10. All
      subjects were admitted to the General Clinical Research Center for determination
      of plasma volume. After 3 days of equilibration to a controlled and standardized
      diet, plasma volume was measured using a modified Evans Blue Dye (T-1824)
      dilution technique. Heart rate at rest was higher in the HT group (105 +/- 12 vs
      74 +/- 6 beats/min), but during submaximum exercise, heart rates in the control
      group increased more rapidly (p < or = 0.05) and to a greater magnitude (54 +/-
      7% vs 17 +/- 4% above rest). Stroke volume at rest was lower in HT recipients (45
      +/- 4 vs 68 +/- 9 ml) but was significantly augmented immediately after onset of
      exercise (30 seconds) and the relative increase was greater than controls at peak
      exercise (61% vs 38% greater than baseline). Cardiac output at rest was within
      the normal range in both groups (4.58 +/- 0.27 vs 4.94 +/- 0.40 L/min). Relative
      increases in cardiac output were similar (p > or = 0.05) for the HT (106 +/- 12%)
      and control groups (97 +/- 10%). Plasma norepinephrine did not become
      significantly greater than resting values until approximately 4 minutes after
      onset of exercise in both groups. Blood volume, normalized for body weight, was
      12% greater in the HT group. Thus, HT recipients with expanded blood volume (12%)
      augment stroke volume immediately after the onset of exercise. Plasma
      norepinephrine levels contribute negligibly to the rapid adjustment in cardiac
      output. Rather, we speculate that abrupt on-transit increases in stroke volume
      are due to augmented venous return, secondary to expanded blood volume.

PMID- 9605059
TI  - Value of a Doppler-derived index combining systolic and diastolic time intervals
      in predicting outcome in primary pulmonary hypertension.
AB  - Primary pulmonary hypertension is characterized by elevated pulmonary arterial
      pressure and vascular resistance, frequently producing right heart failure and
      death. Therefore, the Doppler right ventricular (RV) index, which is a measure of
      global RV function, could be a useful predictor of outcome in primary pulmonary
      hypertension. The Doppler RV index, defined as the sum of isovolumic contraction
      time and isovolumic relaxation time divided by ejection time, was retrospectively
      measured in 53 patients (38 women, aged 45 +/- 14 years) with primary pulmonary
      hypertension. Ejection time was measured from the pulmonary outflow velocity
      signal. The sum of isovolumic contraction time and isovolumic relaxation time was
      obtained by subtracting ejection time from the duration of tricuspid
      regurgitation. The Doppler RV index tended to be elevated (median 0.83) compared
      with normal ranges. Normal Doppler RV index was 0.28 +/- 0.04. After a mean
      follow-up duration of 2.9 years, 4 patients underwent lung transplantation and 30
      patients died; the cause was cardiac in 28, noncardiac in 1, and uncertain in 1.
      Univariately, the Doppler RV index (chi-square 20.7, p <0.0001), severity of
      tricuspid regurgitation (chi-square 8.2, p = 0.004), treatment with calcium
      blockers (chi-square 6.6, p = 0.01), heart rate (chi-square 5.1, p = 0.02), and
      symptom status (chi-square 4.9, p = 0.03) were associated with adverse outcome
      (cardiac deaths and lung transplantation). However, only the Doppler RV index and
      treatment with calcium blockers were independent predictors within the
      multivariate model. Our results indicate that the Doppler RV index is a useful
      predictor of adverse outcome in patients with primary pulmonary hypertension.

PMID- 9605060
TI  - Predicting coronary aneurysms in Kawasaki disease.
AB  - Intravenous immunoglobulin is used to prevent coronary artery involvement in
      patients with acute Kawasaki disease. In this issue of the journal, Beiser et al
      provide a scoring system that is invoked 24 hours after gamma globulin therapy to
      predict risk for coronary involvement. This instrument would be useful for
      pediatric cardiologists and pediatricians in planning later management of
      patients with Kawasaki disease and counseling parents regarding long-term
      outcome.

PMID- 9605061
TI  - Effects of ergotamine on myocardial blood flow in migraineurs without evidence of
      atherosclerotic coronary artery disease.
AB  - The effects of intravenous ergotamine (0.25 mg) on basal and hyperemic
      (dipyridamole) myocardial blood flow (MBF), measured with positron emission
      tomography and H2(15)O, were assessed in 15 migraineurs in a double-blind,
      randomized, placebo controlled, crossover study. Ergotamine produced a 27%
      reduction in hyperemic MBF (2.62 +/- 0.11 vs 3.72 +/- 1.05 ml x min(-1) x g(-1);
      p <0.05), a 31% reduction in the coronary vasodilator reserve (1.81 +/- 0.50 vs
      2.71 +/- 1.15; p <0.01), and a 55% increase in minimal coronary resistance (42.2
      +/- 15 vs 26.7 +/- 8 mm Hg x min x ml(-1) x g(-1); p <0.001), suggesting
      vasoconstriction of the coronary microcirculation.

PMID- 9605062
TI  - Long-term prognosis of 210 patients who underwent coronary angiography before 40
      years of age.
AB  - We report on a follow-up of 210 patients who underwent coronary angiography
      before age 40. We found that young patients with normal coronary arteries have an
      excellent prognosis, whereas those with single-vessel disease have an unfavorable
      outcome resembling that of patients with multivessel disease.

PMID- 9605063
TI  - More on an infant with acute pulmonary toxicity during amiodarone therapy.

PMID- 9605064
TI  - From Ann Arbor to Russia with love: reflections of a little green frog.

PMID- 9605065
TI  - The relationship of ischemia-reperfusion injury of transplanted lung and the up
      regulation of major histocompatibility complex II on host peripheral lymphocytes.
AB  - OBJECTIVES: This study was designed to examine the relationship between ex vivo
      preservation time of the transplanted lung and the extent of injury and to relate
      this to the severity of rejection with and without allogenicity. METHODS: Single
      lung transplantation was performed on two groups of domestic swine. Group A (n =
      7) and group B (n = 6) had ex vivo preservation times of 4 and 15 hours,
      respectively, at 4 degrees C hypothermia. Group C (n = 6) underwent 2 hours of
      warm ischemia via dissection and isolation of the left lung with ligation of its
      bronchial artery and crossclamping of the left pulmonary artery, vein, and
      bronchus without explantation. Assessment measures included lung function,
      antioxidant enzyme activities in the plasma and lung tissue, levels of
      inflammatory mediators in the recipient plasma, and quantification of major
      histocompatibility complex II HLA-DR-beta on host peripheral lymphocytes.
      RESULTS: All groups demonstrated increases in interleukin-10, lung weight, and
      HLA-DR-1beta expression and decreases in lung-tissue antioxidant enzyme
      activities, gas exchange, and lung compliance. There was a strong positive
      correlation between ex vivo preservation time and the expression of HLA-DR-beta
      and a negative correlation between ischemic time and lung-tissue superoxide
      dismutase. CONCLUSIONS: These results suggest that the intensity of the host
      immunogenic response is related to the severity of ischemia-reperfusion injury
      and is independent of tissue incompatibility and/or the type of ischemic insult.
      We conclude that the extension of ex vivo preservation time may predispose the
      transplanted lung to more severe rejection.

PMID- 9605066
TI  - Cardiopulmonary bypass is associated with early allograft dysfunction but not
      death after double-lung transplantation.
AB  - OBJECTIVES: To assess the effect of cardiopulmonary bypass on allograft function
      and recipient survival in double-lung transplantation. METHODS: Retrospective
      review of 94 double-lung transplantations. RESULTS: Cardiopulmonary bypass was
      used in 37 patients (CPB); 57 transplantations were accomplished without bypass
      (no-CPB). Bypass was routinely used for patients with pulmonary hypertension (n =
      27) and for two recipients undergoing en bloc transplantation. Cardiopulmonary
      bypass was required in eight (12.3%) of the remaining 65 patients. Mean ischemic
      time was longer in the CPB group (346 vs 315 minutes, p = 0.04). The CPB group
      required more perioperative blood (11.4 vs 6.0 units, p = 0.01). Allograft
      function, assessed by the arterial/alveolar oxygen tension ratio, was better in
      the no-CPB group at 12 and 24 hours after operation (0.54 vs 0.39 at 12 hours, p
      = 0.002; and 0.63 vs 0.38 at 24 hours, p = 0.001). The CPB group had more severe
      pulmonary infiltrates at both 1 and 24 hours (p = 0.005). Diffuse alveolar damage
      was more common in the CPB group (69% vs 35%, p = 0.002). Median duration of
      intubation was longer in the CPB group (10 days) than in the no-CPB group (2
      days, p = 0.002). The 30-day mortality rate (13.5% vs 7.0% in the CPB and no-CPB
      groups) and 1-year survival (65% vs 67%, CPB and no-CPB) were not significantly
      different. CONCLUSIONS: In the absence of pulmonary hypertension, cardiopulmonary
      bypass is only occasionally necessary in double-lung transplantation. Bypass is
      associated with substantial early allograft dysfunction after transplantation.

PMID- 9605067
TI  - Triple immunosuppression reduces mononuclear cell infiltration and prolongs graft
      life in pig-to-newborn baboon cardiac xenotransplantation.
AB  - OBJECTIVE: Pig hearts transplanted into unmedicated newborn baboons do not
      undergo hyperacute rejection by preformed xenoantibody and complement. These
      grafts are rejected at days 3 to 4 in association with the infiltration of
      macrophages and natural killer cells. We investigated whether an
      immunosuppressive regimen used widely in cardiac allotransplantation could reduce
      this cellular response and prolong xenograft life. METHODS: Ten newborn baboons
      underwent heterotopic pig cardiac xenotransplantation. Five baboons were
      immunosuppressed with mycophenolate mofetil (100 mg/kg), methylprednisolone
      acetate (0.8 mg/kg), and cyclosporine A (INN: ciclosporin; 10 mg/kg). Xenograft
      rejection was studied by light microscopy and immunofluorescence. The induced
      humoral response to porcine xenoantigens was documented by enzyme-linked
      immunosorbent assay using synthetic alpha-1,3-galactosyl epitopes coupled to
      bovine serum albumin. RESULTS: Graft life was extended from a mean of 3.6 +/- 0.5
      days (n = 5) to a mean of 6.2 +/- 1.1 days (n = 5, p = 0.01). In comparison with
      controls, explanted grafts from medicated baboons demonstrated reduced
      infiltration with natural killer cells and macrophages, but increased evidence of
      complement-mediated rejection substantiated by increased deposition of
      immunoglobulin M, complement, and fibrin. In all baboons receiving transplants,
      levels of both immunoglobulin M and immunoglobulin G anti-galactose were
      significantly increased after transplantation, with immunoglobulin G levels
      remaining persistently elevated. CONCLUSIONS: These results indicate that
      cyclosporine-based triple immunosuppression marginally prolonged xenograft
      survival and appears to have reduced the natural killer cell and macrophage
      infiltrates. The immunosuppressive protocol, however, was not adequate to prevent
      the induced immunoglobulin M humoral response and prevent complement-mediated
      graft injury.

PMID- 9605068
TI  - Vascular endothelial growth factor expression in non-small-cell lung cancer:
      prognostic significance in squamous cell carcinoma.
AB  - BACKGROUND: Recently, some studies have focused on the tumor angiogenesis and its
      prognostic value. We studied the expression of vascular endothelial growth
      factor, microvessel counts, and serum concentrations of vascular endothelial
      growth factor to investigate their association with clinicopathologic factors and
      prognosis in non-small-cell lung cancer. METHODS: The expression of vascular
      endothelial growth factor was determined by an immunohistochemical analysis from
      91 paraffin specimens of completely resected non-small-cell lung cancers using
      anti-growth factor polyclonal antibody. Microvessel staining was performed by
      immunohistochemical analysis with anti-factor VIII-related antigen polyclonal
      antibody. Measurement of the serum concentrations of vascular endothelial growth
      factor used the sandwich enzyme-linked immunosorbent assay technique. RESULTS:
      Expression of vascular endothelial growth factor was detected in 48 of the 91
      tumors. The positive ratio was significantly higher in patients with
      adenocarcinoma than in those with squamous cell carcinoma. The microvessel counts
      were significantly higher in the patients with nodal metastasis than in those
      without nodal metastasis. The serum concentrations of vascular endothelial growth
      factor were also significantly higher in the patients with T3-4 disease than in
      those with T1-2 disease. The microvessel counts were closely associated with
      expression of vascular endothelial growth factor. The prognosis of patients with
      a positive growth factor ratio was significantly worse than that of the patients
      with a negative ratio (p = 0.002), especially in squamous cell carcinoma.
      According to a multivariate analysis, only nodal status and expression of
      vascular endothelial growth factor were found to be independent prognostic
      factors. CONCLUSIONS: The expression of vascular endothelial growth factor was
      one of the most important prognostic factors in completely resected non-small
      cell lung cancer, especially in squamous cell carcinoma.

PMID- 9605069
TI  - Clinical analysis of small-sized peripheral lung cancer.
AB  - OBJECTIVE: In Japan, with the initiation of the lung cancer screening program,
      small-sized peripheral lung cancer in which the diameter is 2 cm or less has been
      increasing. The purpose of this study is to determine the clinicopathologic
      behavior of small-sized lung cancer. METHODS: Four hundred ninety-six patients
      with cT1 N0, peripheral, resected non-small-cell lung cancer, who were operated
      on between 1980 and 1996, were selected, grouped by tumor diameter or histologic
      type, and then analyzed for clinicopathologic behavior. On the basis of measured
      diameter roentgenographically, the patients were divided into two groups; group c
      S with lesions 2 cm or less in diameter and group c-L with lesions 2.1 to 3 cm in
      diameter. RESULTS: Lymph node metastasis was recognized in 18% of group c-S, in
      23% of group c-L, and in 21% for the entire clinical group. The rate of those
      with the progressive state was 19% in group c-S and 26% in group c-L. The 5-year
      survival was 79.5% in group c-S and 69.3% in group c-L (i.e., there was a
      significant difference between the two groups). CONCLUSION: Compared with the
      patients with lesions 2.1 to 3 cm in diameter, the patients with small-sized lung
      cancer had a milder progressive state and a better prognosis.

PMID- 9605070
TI  - Artificial placenta--a need for fetal surgery?

PMID- 9605071
TI  - A new artificial placenta with a centrifugal pump: long-term total extrauterine
      support of goat fetuses.
AB  - PURPOSE: We tried long-term total extrauterine support of goat fetuses at high
      pump flow, which was pulsatile and synchronized with the cardiac cycle and at low
      oxygen tension in the umbilical artery and vein by use of the new artificial
      placenta. METHOD: This system consisted of an arteriovenous extracorporeal
      membrane oxygenation using umbilical artery and vein and a thermoregulated water
      bath. Five goat fetuses (125 +/- 0.7 days of gestation, 2.0 +/- 0.9 kg) were
      incubated in lactated Ringer's solution. Mean pump flow rate ranged from 113 +/-
      16 to 193 +/- 13 ml/min/kg, and umbilical arterial oxygen tension was maintained
      at 20 +/- 3 to 23 +/- 5 mm Hg for five fetuses. RESULT: Blood gas analysis
      echocardiogram showed that fetal circulation and sufficient oxygen consumption
      could be maintained, and fetal extrauterine support conditions were made as
      similar as possible to physiologic circulatory conditions. We achieved long-term
      extrauterine support of goat fetuses up to 237 hours (mean 137 +/- 58 hours).
      CONCLUSION: We believe that this system can be used for experimental models of
      the fetus and will come into clinical application for fetal extrauterine support
      systems and backup systems for fetal operations.

PMID- 9605072
TI  - Atrioventricular valve function after single patch repair of complete
      atrioventricular septal defect in infancy: how early should repair be attempted?
AB  - BACKGROUND: Though repair of complete atrioventricular septal defect in infancy
      has become routine at most centers, it is not unusual for very young infants to
      be managed medically because of concerns about the fragility of the
      atrioventricular valve tissue. METHODS: Since July 1992, seventy-two infants have
      undergone primary repair of complete atrioventricular septal defects at a median
      age of 3.9 months (40% < 3 months). A single-patch technique was used in all
      patients. The cleft was closed completely in 61 patients and partially (n = 10)
      or not at all (n = 1) in select patients at risk for valve stenosis. Left
      atrioventricular valve annuloplasty was performed in 18 patients. On the basis of
      transesophageal echocardiographic findings, 10 patients were returned to bypass
      for revision of the valve repair. RESULTS: There was one early death in a patient
      with single left papillary muscle, no early reoperations, and no new permanent
      arrhythmias. Only three patients had moderate left atrioventricular valve
      regurgitation at discharge. During a median follow-up of 24 months, there was one
      late death and five reoperations for left atrioventricular valve regurgitation (n
      = 2) and/or systemic outflow obstruction (n = 4). Follow-up left atrioventricular
      valve regurgitation was moderate in three patients, mild in 14, and none/trace in
      54. Age had no relation to postoperative atrioventricular valve regurgitation,
      death, or reoperation. CONCLUSIONS: Despite concerns about fragility of valve
      tissue in very young patients, excellent results can be achieved with meticulous
      techniques. From neonates to older infants, age at repair does not influence
      outcome or valve function.

PMID- 9605073
TI  - Neonatal thymectomy: does it affect immune function?
AB  - OBJECTIVE: The purpose of this study was to determine whether thymectomy in the
      newborn has a negative effect on immune function. METHODS: Twenty-five neonates
      (<30 days) who had thymectomy at congenital heart repair were prospectively
      studied to determine immune function. The percentage of T-cell subtypes including
      CD3 (all T cells), CD4 (helper T cells), and CD8 (suppressor T cells) was
      determined. In six patients, further testing of CD4 cells was done to determine
      whether they were newly formed, recent thymic emigrants (CD4, CD45, and RA+), or
      older educated lymphocytes (CD4, CD45, and RO+). Response to the mitogen
      phytohemagglutinin and to tetanus toxoid were determined, as were antibody titers
      to tetanus. Samples were drawn before the thymectomy, at approximately 3 months
      after immunization and at 1 year. Ten age-matched control patients were tested.
      At follow-up, parents were asked about infections. RESULTS: Prethymectomy T-cell
      subsets were all normal and comparable to controls. At 12 months, the percent of
      CD3 was significantly less than in the control group (48% +/- 3% versus 64% +/-
      2% [mean +/- standard error of the mean]; p < 0.01) as was CD4 (31% +/- 2% versus
      46% +/- 2% [mean +/- standard error of the mean]; p = < 0.01). CD8 did not drop.
      Surprisingly, the percent of CD4 that were recent thymic emigrants did not
      decrease significantly (50% +/- 8% versus 60% +/- 6% [mean +/- standard error of
      the mean]; p = not significant). Lymphocyte blastogenesis to phytohemagglutinin
      and tetanus toxoid and antibody to tetanus were all normal at 12 months. No
      patient required readmission for infection, and there were the expected number of
      minor infectious events (median 3; 95% confidence interval 1,4). CONCLUSION:
      Thymectomy in neonates results in a modest but significant decrease in T
      lymphocyte levels, but there is no compromise in immune function.

PMID- 9605074
TI  - Endothelial dysfunction in cerebral microcirculation during hypothermic
      cardiopulmonary bypass in newborn lambs.
AB  - OBJECTIVES: Inflammatory stimuli or mechanical stresses associated with
      hypothermic cardiopulmonary bypass could potentially impair cerebrovascular
      function, resulting in inadequate cerebral perfusion. We hypothesize that
      hypothermic cardiopulmonary bypass is associated with endothelial or vascular
      smooth muscle dysfunction and associated cerebral hypoperfusion. Therefore we
      studied the cerebrovascular response to endothelium-dependent vasodilator,
      acetylcholine, endothelium-independent nitric oxide donor, sodium nitroprusside,
      and vasoactive amine, serotonin, in newborn lambs undergoing hypothermic
      cardiopulmonary bypass (nasopharygeal temperature = 18 degrees C). METHODS:
      Studies were performed on 13 newborn lambs equipped with a closed cranial window,
      allowing for direct visualization of surface pial arterioles. Six animals were
      studied while undergoing hypothermic cardiopulmonary bypass, whereas seven served
      as nonbypass, warm (37 degrees C) controls. Pial arteriolar caliber (range = 111
      to 316 microm diameter) was monitored using video microscopy. RESULTS: Topical
      application of acetylcholine caused a dose-dependent increase in arteriolar
      diameter in the control group that was absent in animals undergoing hypothermic
      cardiopulmonary bypass. Hypothermic cardiopulmonary bypass did not alter the
      vasodilation in response to sodium nitroprusside. Furthermore, the contractile
      response to serotonin was fully expressed during hypothermic cardiopulmonary
      bypass. CONCLUSIONS: The specific loss of acetylcholine-induced vasodilation
      suggests endothelial cell dysfunction rather than impaired ability of vascular
      smooth muscle to respond to nitric oxide. It is speculated that loss of
      endothelium-dependent regulatory factors in the cerebral microcirculation during
      hypothermic cardiopulmonary bypass may enhance vasoconstriction, and impaired
      cerebrovascular function may be a basis for associated neurologic injury during
      or after hypothermic cardiopulmonary bypass.

PMID- 9605075
TI  - Growth of the right ventricle after successful transcatheter pulmonary valvotomy
      in neonates and infants with pulmonary atresia and intact ventricular septum.
AB  - OBJECTIVES: Since 1990, transcatheter pulmonary valvotomy has become an
      alternative to surgical valvotomy in the management of neonates and infants with
      pulmonary atresia and intact ventricular septum. We sought to determine whether
      right ventricular growth after transcatheter pulmonary valvotomy is commensurate
      with body growth. METHODS: Laser or radiofrequency-assisted balloon valvotomy was
      attempted in 12 neonates and infants with pulmonary atresia and intact
      ventricular septum. Tricuspid and mitral valve dimensions were measured
      retrospectively on the cross-sectional echocardiograms performed before the
      procedure and during follow-up. Z-values were used to standardize tricuspid valve
      dimensions with body size. RESULTS: The atretic pulmonary valve was successfully
      perforated and dilated in nine of 12 patients. Five of these nine patients
      required additional transcatheter or surgical procedures to augment the pulmonary
      blood flow. Of six survivors, five are regularly followed up with a median follow
      up of 60 months (range 37 to 68 months). All five have two-ventricle circulation,
      two of the five patients requiring surgical enlargement of the right ventricular
      outflow tract with or without closure of the atrial septal defect.
      Echocardiographic tricuspid valve dimensions and Z-values before transcatheter
      valvotomy tended to be smaller in the patients who died than in the survivors. In
      the survivors, the absolute tricuspid valve dimensions increased after valvotomy
      but the Z-values tended to decrease or stayed constant. CONCLUSIONS:
      Transcatheter valvotomy is a good alternative to surgical valvotomy in patients
      with pulmonary atresia and intact ventricular septum. Two-ventricle circulation
      can be achieved despite subnormal right ventricular growth.

PMID- 9605076
TI  - Protein-losing enteropathy after the Fontan operation: an international
      multicenter study. PLE study group.
AB  - OBJECTIVE: This multicenter study retrospectively analyzes the data on 114
      patients with protein-losing enteropathy after Fontan-type surgery. Special
      attention was given to the different treatment strategies used and their effect
      on outcome. METHODS AND RESULTS: In 35 participating centers 3029 Fontan
      operations were performed. The incidence of protein-losing enteropathy in the
      survivors was 3.7%. The median age at Fontan-type surgery was 8.2 years (range:
      0.6 to 32.9 years). Median age at diagnosis of protein-losing enteropathy was
      11.7 years with a median time interval between surgery and diagnosis of 2.7 years
      (range: 0.1 to 16.4 years). Most patients had edema (79%) and effusions (75%).
      Hemodynamic data revealed a mean right atrial pressure of 17 +/- SD 5.3 mm Hg
      with a cardiac index of 2.4 +/- 0.8 L/min/m2. Medical treatment only (n = 52)
      resulted in a complete resolution of symptoms in 25%, no improvement in 29%, and
      death in 46%. Surgical treatment (n = 52) was associated with relief of protein
      losing enteropathy in 19%, no improvement in 19%, and death in 62%. In 13
      patients 16 percutaneous interventions were performed. This resulted in
      symptomatic improvement after 12 interventions and no improvement after 4
      interventions. CONCLUSIONS: We conclude that the current treatment of protein
      losing enteropathy after Fontan operation is associated with a very high
      mortality and morbidity rate. Preventive strategies and new therapeutic
      approaches are necessary.

PMID- 9605077
TI  - Mechanical valves in the pulmonary position: a reappraisal.
AB  - OBJECTIVES: To evaluate midterm results of mechanical valves in pulmonary
      position in patients with pulmonary regurgitation and right ventricular
      dysfunction as an alternative to bioprostheses. PATIENTS: Mechanical valves (six
      tilting disc valves and two bileaflet valves) were implanted in eight patients
      previously operated on for tetralogy of Fallot (n = 7) and truncus arteriosus (n
      = 1), with severe right ventricular dysfunction caused by massive pulmonary
      regurgitation. RESULTS: All patients survived prosthesis implantation and are
      currently well. At follow-up (3 months to 9 years), they do not show signs of
      valve failure, and right ventricular function has dramatically improved in all
      but one, who still shows moderate ventricular hypokinesia. CONCLUSION: After
      operative correction of congenital heart defects in selected patients who show
      severe dysfunction of the right ventricle caused by pulmonary
      regurgitation/stenosis, mechanical valves may represent an alternative to
      bioprosthetic valves. The selection of the valve type is still a matter of
      debate. However, according to literature data, complications seem to have
      occurred only in patients with bileaflet mechanical valves in the pulmonary
      position, whereas no thromboembolic episodes or valve failure is reported in
      subjects with tilting disc valves in the right ventricular outflow. Tilting disc
      valves might perform better in the right ventricular outflow than bileaflet
      valves.

PMID- 9605078
TI  - Late results of a valve-preserving operation in patients with aneurysms of the
      ascending aorta and root.
AB  - OBJECTIVES: There is still no agreement about the best method of dealing with
      malfunction of the aortic valve caused by aneurysm or dissection of the aortic
      root. The experience, rationale, and development of a valve-preserving technique
      introduced and used since 1979 is described. METHODS: During this period 158
      patients (78% of all patients undergoing resection of aneurysm of the ascending
      aorta) were operated on using this technique. Their ages ranged from 2 to 72
      years (mean 46.6 years). Of the patients 107 were male and 51 were female. A
      total of 68 patients had skeletal manifestations of Marfan's syndrome. The
      original disease was chronic aneurysm of the ascending aorta or root in 92
      (58.2%), chronic dissection in 17 (10.8%), and acute dissection in 49 (31%)
      patients. One hundred eleven additional procedures were performed in 84 patients.
      In all there were five early deaths (4.6% +/- 2%) in the 109 patients with
      chronic aneurysm and one death in the 103 patients operated on electively (0.97%
      +/- 0.9%). Actuarial survival for patients operated on for chronic aneurysm was
      93.3%, 88.0%, 79.0%, and 57.9% at 1, 5, 10, and 15 years and 96.8%, 91.2%, 82.0%,
      and 60.0% for those operated on electively. Actuarial survival for patients
      operated on for acute dissection was 72.8%, 63.4%, and 53.3% at 1, 5, and 10
      years. The probability of needing reoperation was 3.0% +/- 2%, 11% +/- 0.5%, and
      11% +/- 0.5% at 1, 5, and 10 years. There were no instances of infective
      endocarditis or thromboembolic complications except in two patients operated on
      early in the series who had cusp extension. No anticoagulants were used.
      Echocardiography showed reduction in left ventricular end-systolic and end
      diastolic dimensions, which was maintained. At the end of follow-up trivial or no
      aortic regurgitation was demonstrated in 63.6%, mild to moderate in 33.3%, and
      severe in 3%. CONCLUSIONS: Valve-sparing operations are possible in a large
      proportion of patients with aneurysms of the ascending aorta and the medium and
      long-term results are encouraging.

PMID- 9605079
TI  - Ten years of experience with the modified Ross procedure.
AB  - BACKGROUND: To assess the full root modification of the Ross procedure, we
      examined operative and long-term results. METHODS: We retrospectively reviewed
      145 patients (118 men and 27 women) operated on from March 1987 through April
      1997. Ages ranged from 17 to 68 years. Primary diagnosis was aortic stenosis in
      43 patients (29.6%) and aortic regurgitation in 62 patients (42.8%). There was
      mixed disease (stenosis and regurgitation) in 40 patients (29.6%) of whom the
      vast majority had predominant stenosis. RESULTS: Early death was 7 of 145
      patients (4.8%). Twelve patients had 14 significant complications (8.5%). There
      were four late deaths. Overall patient survival is 90.5% +/- 3.1% at 5 years and
      84.5% +/- 14.1% at 7 years. Endocarditis occurred in three patients-two on the
      autograft and one on the pulmonary homograft. Three patients had cerebrovascular
      accidents. In 5 of 132 patients (3.8%) reoperations were required on the
      autograft. Freedom from autograft reoperation was 93.9% +/- 3.1% at 5 years and
      88.6% +/- 6.4% at 7 years. Echocardiographic follow-up reveals more than mild
      aortic regurgitation in only nine patients, including the five patients in whom
      reoperations were required. Seven of 11 patients with active endocarditis at the
      time of the operation had adverse outcomes. CONCLUSIONS: Ten years' experience
      with the modified Ross procedure has shown excellent results with regard to short
      and long-term morbidity and death. It is the procedure of choice for young
      patients who need aortic valve replacement but should be used with caution in the
      setting of active endocarditis.

PMID- 9605080
TI  - Minimally invasive port-access coronary artery bypass grafting with early
      angiographic follow-up: initial clinical experience.
AB  - OBJECTIVE: New techniques for minimally invasive coronary artery bypass grafting
      have recently emerged. The purpose of this study was to determine the safety and
      efficacy of Port-Access (Heartport, Inc., Redwood City, Calif.) coronary
      revascularization and to evaluate with angiography the early graft patency rate
      with this new approach. METHODS: From October 1996 to May 1997, 31 patients
      underwent Port-Access coronary artery bypass grafting with an anterior
      minithoracotomy and endovascular-occlusion cardiopulmonary bypass. There were 26
      men and 5 women with a mean age of 62 years (range 42 to 82 years). Fifteen
      patients underwent single bypass; 12 patients underwent double bypass, and 4
      patients underwent triple bypass. Bypass conduits included the left internal
      thoracic artery (n = 30), right internal thoracic artery (n = 2), radial artery
      (n = 10), and saphenous vein (n = 6). Three sequential grafts were used.
      Angiographic studies of the bypass grafts were performed in 27 of 31 patients
      (87%). RESULTS: There were no deaths, neurologic deficits, myocardial
      infarctions, or aortic dissections. Conversion to sternotomy was not required in
      any case. There were two reoperations for bleeding, one reoperation for
      tamponade, and one reoperation for pulmonary embolus. Postoperative angiography
      revealed anastomotic patency of the left internal thoracic artery to left
      anterior descending artery in 26 of 26 grafts (100%) with overall anastomotic
      patency in 43 of 44 grafts (97.7%). CONCLUSION: These results demonstrate that
      Port-Access coronary artery bypass can be performed accurately and safely with
      acceptable morbidity. This approach allows for multivessel revascularization on
      an arrested, protected heart with excellent anastomotic precision and
      reproducible early graft patency.

PMID- 9605081
TI  - Heparinization on pericardial substitutes can reduce adhesion and epicardial
      inflammation in the dog.
AB  - OBJECTIVE: Primary concerns about currently available pericardial substitutes
      include adhesion and epicardial reaction. The purpose of this study is to
      evaluate host reaction to pericardial substitutes with and without incorporating
      slow heparin release. METHODS: To avoid biologic variation among these
      pericardial patches, we made a composite of six membranes. The composite membrane
      consisted of epoxy-fixed patches with (1) or without (2) ionically bound heparin,
      a glutaraldehyde-fixed patch with (3) or without (4) ionically bound heparin, an
      expanded polytetrafluoroethylene patch (5), and a polyester polymeric patch (6).
      Ten recipient dogs weighing from 12 to 19 kg (mean 13.6 kg) were used to assess
      the composite membranes as pericardial substitutes. The implanted composite
      membranes were retrieved 1 week (one dog), 2 weeks (one dog), 4 weeks (one dog),
      8 weeks (one dog), and 12 weeks (six dogs) after implantation. RESULTS: Overall,
      the synthetic patches had a more notable inflammatory reaction than the biologic
      patches with or without ionically bound heparin. The heparin-bound patches caused
      significantly less inflammation than their nonheparinized counterparts. The
      heparinized porcine patches cross-linked with different compounds were found to
      have less fibrous formation than the nonheparinized patches and the synthetic
      patches. CONCLUSIONS: Heparinized pericardial substitutes may cause less adhesion
      and inflammatory reaction than nonheparinized material.

PMID- 9605082
TI  - Long-term results of heart valve replacement with the Edwards Duromedics
      bileaflet prosthesis: a prospective ten-year clinical follow-up.
AB  - OBJECTIVE: The Edwards Duromedics valve (Baxter Healthcare Corp., Edwards
      Division, Santa Ana, Calif.) was designed with a self-irrigating hinge mechanism
      to reduce thromboembolic complications. After good initial clinical results,
      distribution was suspended in 1988 after reports of valve fracture after 20,000
      valves had been implanted. The manufacturer conducted extensive studies to
      improve the Edwards Duromedics and reintroduced a modified version, which is
      available as Edwards Tekna. The purpose of the study was the evaluation of long
      term results of the original Edwards Duromedics that might be important for the
      current version, the Edwards Tekna valve. METHODS: A prospective clinical 10-year
      follow-up was performed of 508 patients who underwent valve replacement with the
      Edwards Duromedics valve in the aortic (n = 268), mitral (n = 183), and aortic
      and mitral (n = 56) position. RESULTS: The perioperative mortality rate was 6.9%;
      follow-up was 98% complete, comprising 3648 patient-years for a mean follow-up of
      86 months (range: 33 to 144 months). The actuarial freedom from complications at
      the 10-year follow-up and the incidence rate (percent per patient-year) were as
      follows: late mortality rate, 69.2% +/- 2.4% (3.5% per patient-year);
      thromboembolism, 90.7% +/- 1.6% (0.96% per patient-year); anticoagulation-related
      hemorrhage, 87.7% +/- 1.7% (1.34% per patient-year); prosthetic valve
      endocarditis, 96.7% +/- 0.09% (0.38% per patient-year); valve-related mortality
      rate, 89.3% +/- 1.6% (1.21% per patient-year); valve failure, 86.2% +/- 1.85%
      (1.54% per patient-year); and valve-related morbidity and mortality rate, 71.1%
      +/- 2.3% (3.2% per patient-year). Three leaflet escapes were observed (one
      lethal, two successful reoperations; 99.1% +/- 0.05% freedom, 0.08% per patient
      year). All patients functionally improved (86% in New York Heart Association
      classes I and II), and incidence of anemia was insignificant. CONCLUSIONS: These
      results confirm that the Edwards Duromedics valve shows excellent performance
      concerning thromboembolism, hemolysis, and functional improvement and will serve
      as a reference for the last version, the Edwards Tekna valve, where comparable
      long-term data are currently not available.

PMID- 9605083
TI  - Repair of nonsevere rheumatic aortic valve disease during other valvular
      procedures: is it safe?
AB  - OBJECTIVE: To investigate the long-term performance of aortic valve repair, we
      analyzed the results obtained in a 22-year period in patients who underwent
      repair of nonsevere rheumatic aortic valve disease during other valvular
      procedures. METHODS: Fifty-three patients (mean 40 +/- 11.6 years of age) with
      predominant rheumatic mitral valve disease had concomitant aortic valve disease
      in association with serious tricuspid valve disease in 25 of them.
      Preoperatively, aortic valve disease was considered moderate in 47.2% of the
      patients and mild in 52.8%. All patients underwent reparative techniques of the
      aortic valve (free edge unrolling, 44; subcommissural annuloplasty, 40;
      commissurotomy, 36) at the time of mitral or mitrotricuspid valve surgery. The
      completeness of follow-up during the closing interval was 100%, with a mean
      follow-up of 18.8 years (range 8 to 22.5 years). RESULTS: Hospital mortality rate
      was 7.5%. Of 49 surviving patients, 26 (53.1%) died during late follow-up. The
      actuarial survival curve including hospital mortality was 35.4% +/- 8.7% at 22
      years. For patients who underwent mitral and aortic valve surgery, the actuarial
      survival curve at 22 years was 32.3% +/- 13%, whereas for patients who had a
      triple-valve operation the survival was 37.0% +/- 10.1% (p = 0.07). Twenty-five
      patients underwent an aortic prosthetic valve replacement. Actuarial free from
      aortic structural deterioration and valve-related complications at 22 years was
      25.3% +/- 9.3% and 12.7% +/- 4.8%, respectively. CONCLUSIONS: Long-term
      functional results of reparative procedures of nonsevere aortic valve disease in
      patients with predominant rheumatic mitral valve disease have been inadequate at
      22 years of follow-up. According to these data, conservative operations for
      rheumatic aortic valve disease do not seem appropriate.

PMID- 9605084
TI  - Characteristics of adrenoceptors in the human radial artery: clinical
      implications.
AB  - OBJECTIVES: The radial artery has been suggested to be spastic. Endogenous and
      exogenous catecholamines and the use of beta-blockers may be related to radial
      artery spasm, but the characteristics of adrenoceptors in this artery are
      unknown. This study was designed to characterize the alpha- and beta-adrenoceptor
      in the human radial artery. METHODS: Ring segments of the radial artery (n = 59)
      taken from patients undergoing coronary artery bypass grafting were studied in
      organ chambers. Alpha-adrenoceptor agonists (norepinephrine, methoxamine, and
      UK14304) and antagonists (phentolamine hydrochloride [INN: phentolamine],
      prazosin, and yohimbine) were used to characterize the alpha-adrenoceptor. Beta
      adrenoceptor function was studied in U46619-precontracted rings in response to
      isoproterenol (INN: isoprenaline). RESULTS: Norepinephrine induced 6.9 +/- 0.6 gm
      (80.6% +/- 6.8% of the contraction by 100 mmol/L KCl), and this was almost fully
      inhibited by phentolamine hydrochloride (10 micromol/L, p < 0.0001). The
      contraction force induced by methoxamine (2.9 +/- 0.8 gm) was abolished by 0.5
      micromol/L prazosin (p = 0.017). The contraction force induced by UK14304 (1.7 +/
      0.4 gm) was abolished by 1 micromol/L yohimbine. In contrast to the porcine
      coronary artery used as the control (fully relaxed to isoproterenol), radial
      artery rings did not have significant relaxation (1.1% +/- 0.8%). CONCLUSIONS:
      The human radial artery is an alpha-adrenoceptor-dominant artery with little beta
      adrenoceptor function. The use of beta-blockers will not likely evoke the spasm
      of the radial artery. Furthermore, the radial artery has a dominant alpha1
      adrenoceptor function, but the postjunctional alpha2-adrenoceptor is also
      functional. Circulating catecholamines will mainly contract the human radial
      artery by activation of the alpha1-adrenoceptors and to a lesser extent also by
      alpha2-adrenoceptors.

PMID- 9605085
TI  - Can retrograde perfusion mitigate cerebral injury after particulate embolization?
      A study in a chronic porcine model.
AB  - OBJECTIVE: We assessed the impact on histologic and behavioral outcome of an
      interval of retrograde cerebral perfusion after arterial embolization, comparing
      retrograde cerebral perfusion with and without inferior vena caval occlusion with
      continued antegrade perfusion. METHODS: Sixty Yorkshire pigs (27 to 30 kg) were
      randomly assigned to the following groups: antegrade cerebral perfusion control;
      antegrade cerebral perfusion after embolization; retrograde cerebral perfusion
      control; retrograde cerebral perfusion after embolization; retrograde cerebral
      perfusion with inferior vena cava occlusion, retrograde cerebral perfusion with
      inferior vena cava occlusion control, and retrograde cerebral perfusion with
      inferior vena cava occlusion after embolization. After cooling to 20 degrees C, a
      bolus of 200 mg of polystyrene microspheres 250 to 750 (microm diameter (or
      saline solution) was injected into the isolated aortic arch. After 5 minutes of
      antegrade cerebral perfusion, 25 minutes of antegrade cerebral perfusion,
      retrograde cerebral perfusion, or retrograde cerebral perfusion with inferior
      vena cava occlusion was instituted. After the operation, all animals underwent
      daily assessment of neurologic status until the time of death on day 7. RESULTS:
      Aortic arch return, cerebral vascular resistance, and oxygen extraction data
      during retrograde cerebral perfusion showed differences, suggesting that more
      effective flow occurs during retrograde cerebral perfusion with inferior vena
      cava occlusion, which also resulted in more pronounced fluid sequestration.
      Microsphere recovery from the brain revealed significantly fewer emboli after
      retrograde cerebral perfusion with inferior vena cava occlusion. Behavioral
      scores showed full recovery in all but one control animal (after retrograde
      cerebral perfusion with inferior vena cava occlusion) by day 7 but were
      considerably lower after embolization, with no significant differences between
      groups. The extent of histopathologic injury was not significantly different
      among embolized groups. Although no histopathologic lesions were present in
      either the antegrade cerebral perfusion control group or the retrograde cerebral
      perfusion control group, mild significant ischemic damage occurred after
      retrograde cerebral perfusion with inferior vena cava occlusion even in control
      animals. CONCLUSIONS: Although effective washout of particulate emboli from the
      brain can be achieved with retrograde cerebral perfusion with inferior vena cava
      occlusion, no advantage of retrograde cerebral perfusion with inferior vena cava
      occlusion after embolization is seen from behavioral scores,
      electroencephalographic recovery, or histopathologic examination; retrograde
      cerebral perfusion with inferior vena cava occlusion results in greater fluid
      sequestration and mild histopathologic injury even in control animals. Retrograde
      cerebral perfusion with inferior vena cava occlusion shows clear promise in the
      management of embolization, but further refinements must be sought to address its
      still worrisome potential for harm.

PMID- 9605086
TI  - Disappearance of glycoprotein Ib from the platelet surface in pericardial blood
      during cardiopulmonary bypass.
AB  - OBJECTIVES: Several investigators have reported decreased expression of
      glycoprotein Ib on the platelet surface during coronary artery bypass grafting,
      but others could not confirm this finding. Because platelet glycoprotein Ib
      functions as an adhesion receptor for von Willebrand factor and other adhesive
      proteins, this decreased expression may explain excessive postoperative blood
      loss. In this study the expressions of glycoprotein Ib and other platelet
      activation markers were studied in the systemic and pericardial blood of seven
      patients undergoing coronary artery bypass grafting. Pericardial blood was
      recently shown to have high activation levels of fibrinolytic and coagulation
      pathways; we hypothesized that this local blood activation might be paralleled by
      extensive platelet activation and associated disappearance of glycoprotein Ib.
      METHODS: Expression of platelet surface antigens was determined by whole-blood
      double-label flow cytometry. RESULTS: Glycoprotein Ib expression in systemic
      blood decreased 10% (p = 0.03) from preoperative levels at the start of
      cardiopulmonary bypass and 30% (p = 0.04) before release of the aortic
      crossclamp. Expression in pericardial blood at these times decreased by 50% and
      51%, respectively (p = 0.003, p = 0.009). No changes were observed in the
      expression of the platelet activation antigens CD62P (P-selectin, indicating
      platelet alpha-granular release) and CD63 (indicating lysosomal release) or in
      binding of monoclonal antibody PAC-1 (detecting the fibrinogen-binding receptor
      conformation of the glycoprotein IIb-IIIa complex). CONCLUSION: Glycoprotein Ib
      disappeared from the platelet surface during bypass grafting, most notably in
      pericardial blood. No increased expression of CD62P, CD63, or PAC-1 was found,
      indicating the absence of general platelet activation.

PMID- 9605087
TI  - Prospective, randomized trial comparing blood and oxygenated crystalloid
      cardioplegia in reoperative coronary artery bypass grafting.
AB  - OBJECTIVES: Reoperative coronary artery bypass grafting presents unique
      challenges for myocardial preservation. The purpose of this study was to compare
      oxygenated blood cardioplegia with oxygenated crystalloid cardioplegia during
      reoperative coronary artery bypass grafting using transesophageal
      echocardiography to assess regional wall motion of the left ventricle before and
      after cardiopulmonary bypass. METHODS: Sixty-one patients undergoing reoperative
      coronary artery bypass grafting were prospectively randomized to receive
      oxygenated blood cardioplegia or oxygenated crystalloid cardioplegia delivered
      with a combined antegrade-retrograde technique. Transgastric short axis views of
      the left ventricle were made with transesophageal echocardiography during the
      operation before cardiopulmonary bypass and immediately after cardiopulmonary
      bypass. Regional wall motion was graded by a blinded observer, and before
      cardiopulmonary bypass scores were compared with after cardiopulmonary bypass
      scores. RESULTS: No significant differences were found in the change in regional
      wall motion score from before cardiopulmonary bypass to after cardiopulmonary
      bypass between the blood and crystalloid cardioplegia groups. CONCLUSIONS: This
      study found blood and crystalloid cardioplegia to be equally efficacious for
      myocardial preservation during reoperative coronary artery bypass grafting.

PMID- 9605088
TI  - Down-regulation of surface monocyte lipopolysaccharide-receptor CD14 in patients
      on cardiopulmonary bypass undergoing aorta-coronary bypass operation.
AB  - OBJECTIVES: Major operative trauma like aorta-coronary bypass operation may lead
      to postoperative immunodisturbance, putting the patient at an increased risk for
      infection and sepsis. The monocyte/macrophage system and the endotoxin receptor
      CD14 are important in the early recognition and elimination of invading bacteria.
      The aim of this study was to analyze changes in membrane-associated CD14 and
      soluble CD14 during and after cardiac involving cardiopulmonary bypass. METHODS:
      We studied numbers of leukocytes, monocytes, and monocyte subpopulations,
      expression of monocyte membrane-associated CD14 and plasma levels of soluble CD14
      in 10 patients (63 +/- 8 years of age), who underwent elective cardiopulmonary
      bypass. RESULTS: Cardiopulmonary bypass induced marked postoperative monocytosis,
      which was maximal 20 hours after the operation (485 +/- 242 cells/microl before,
      1080 +/- 264 cells/microl 20 hours after surgery). Expression of membrane
      associated CD14 on classical CD14++ monocytes decreased significantly by 40%,
      reaching a nadir 20 hours after surgery (p < 0.05). At the time of maximal
      membrane-associated CD14 suppression, the levels of soluble CD14 measured by
      enzyme-linked immunosorbent assay were clearly increased (3.2 +/- 1.0 microg/ml
      before versus 5.6 +/- 1.0 microg/ml 20 hours after, p < 0.001). No significant
      change of the percentage of small (alpha) and large (beta) forms of soluble CD14
      was found. CONCLUSIONS: Cardiopulmonary bypass leads to reduced membrane
      associated CD14 expression on peripheral blood monocytes and increased levels of
      soluble CD14 through shedding or secretion of membrane-associated CD14 from the
      cell surface. These findings indicate that bypass is associated with significant
      monocyte activation.

PMID- 9605089
TI  - Heparinless cardiopulmonary bypass with active-site blocked factor IXa: a
      preliminary study on the dog.
AB  - OBJECTIVE: Cardiopulmonary bypass is a potent stimulus for activation of
      procoagulant pathways. Heparin, the traditional antithrombotic agent, however, is
      often associated with increased perioperative blood loss because of its multiple
      sites of action in the coagulation cascade and its antiplatelet and
      profibrinolytic effects. Furthermore, heparin-mediated immunologic reactions
      (that is, heparin-induced thrombocytopenia) may contraindicate its use.
      Cardiopulmonary bypass with a selective factor IXa inhibitor was tested to see
      whether it could effectively limit bypass circuit/intravascular space thrombosis
      while decreasing extravascular bleeding, thereby providing an alternative
      anticoagulant strategy when heparin may not be safely administered. METHODS:
      Active site-blocked factor IXa, a competitive inhibitor of the assembly of factor
      IXa into the factor X activation complex, was prepared by modification of the
      enzyme's active site by the use of dansyl glutamic acid-glycine-arginine
      chlormethylketone. Twenty mongrel dogs (five were given standard
      heparin/protamine; 15 were given activated site-blocked factor IXa doses ranging
      from 300 to 600 microg/kg) underwent 1 hour of hypothermic cardiopulmonary
      bypass, and blood loss was monitored for 3 hours after the procedure. RESULTS:
      Use of activated site-blocked factor IXa as an anticoagulant in cardiopulmonary
      bypass limited fibrin deposition within the extracorporeal circuit as assessed by
      scanning electron microscopy, comparable with the antithrombotic effect seen with
      heparin. In contrast to heparin, effective antithrombotic doses of activated site
      blocked factor IXa significantly diminished blood loss in the thoracic cavity and
      in an abdominal incisional bleeding model. CONCLUSION: These initial studies on
      the dog suggest that administration of activated site-blocked factor IXa may be
      an effective alternative anticoagulant strategy in cardiopulmonary bypass when
      heparin is contraindicated, affording inhibition of intravascular/extracorporeal
      circuit thrombosis with enhanced hemostasis in the surgical wound.

PMID- 9605090
TI  - Prevention of cellular edema directly caused by hypothermic cardioplegia: studies
      in isolated human and rabbit atrial myocytes.
AB  - OBJECTIVES: This study tested the hypothesis that edema during hypothermic
      cardioplegia is caused by the hypotonicity of the perfusate at cold temperatures.
      METHODS: The volume of isolated human and rabbit atrial myocytes was measured by
      video microscopy under nonischemic conditions. Each cell served as its own
      control. RESULTS: After equilibration in 37 degrees C physiologic buffer
      (Tyrode's solution), exposure to 9 degrees C St. Thomas' Hospital solution for 20
      minutes caused human atrial cells to swell by 20% and rabbit atrial cells to
      swell by 10%. Cell volume fully recovered on rewarming in 37 degrees C
      physiologic solution. Cell swelling was due to the composition of St. Thomas'
      Hospital solution rather than hypothermia alone. Exposure to 9 degrees C
      physiologic solution did not significantly affect cell volume. Swelling of
      myocytes was largely prevented by replacing most of the Cl- in St. Thomas'
      Hospital solution with an impermeant anion so that the product of the
      concentrations of K+ and Cl- were the same as in the physiologic solution.
      CONCLUSIONS: This study suggests that cell swelling during hypothermic
      cardioplegia is caused in part by the composition of the cardioplegic solution.
      The volume of cardiac myocytes appears to follow a Donnan equilibrium in the
      cold, and the perfusate KCl product determines water movement. Thus, the tonicity
      of hyperkalemic cardioplegic solutions can be adjusted to a physiologic value by
      replacing most Cl- by an impermeant anion. Following this simple principle, a
      reformulation of cardioplegic solutions may be able to minimize iatrogenic
      myocardial edema.

PMID- 9605091
TI  - Prevention of cell swelling with low chloride St. Thomas' Hospital solution
      improves postischemic myocardial recovery.
AB  - OBJECTIVE: In isolated myocytes cardioplegia-induced cell swelling can be
      prevented by lowering the KCl product by replacing Cl- with an impermeant ion.
      This study tested the hypothesis that Cl- substitution in St. Thomas' Hospital
      cardioplegic solution would result in superior myocardial protection in the
      intact, blood-perfused heart. METHODS: Using a parabiotic, isolated rabbit heart
      Langendorff model, hearts were exposed to 1 hour of hypothermic (10 degrees to 12
      degrees C), global ischemia followed by 30 minutes of reperfusion. Isosmotic
      cardioplegia was administered as a single 50 ml bolus of either standard St.
      Thomas' Hospital solution ([K+]o x [Cl-]o = 2566.4 (mmol/L)2) or low Cl- St.
      Thomas' Hospital solution ([K+]o x [CI-]o = 700 (mmol/L)2). Chloride was replaced
      by a large, impermeant ion, methanesulfonate. Postreperfusion systolic function
      and atrioventricular conduction times were measured before ischemia and after
      reperfusion. RESULTS: Hearts receiving low Cl- St. Thomas' Hospital cardioplegia
      demonstrated significantly better postischemic functional recovery (74% +/- 3%)
      compared with those treated with standard high Cl- St. Thomas' Hospital solution
      (55% +/- 4%, p = 0.003). In addition, atrioventricular conduction times remained
      normal in the low Cl- group but were significantly prolonged in the St. Thomas'
      Hospital group. CONCLUSIONS: Lowering the KCl product of St. Thomas' Hospital
      solution makes it isotonic with plasma and prevents cellular edema. This
      ameliorates the detrimental functional and electrophysiologic sequelae of
      hypothermic, hyperkalemic cardioplegia.

PMID- 9605092
TI  - Hemodilution and whole body oxygen balance during normothermic cardiopulmonary
      bypass in dogs.
AB  - OBJECTIVE: The purpose of this study was to determine the minimum hematocrit
      value that can support whole body oxygen consumption during normothermic
      cardiopulmonary bypass. The effect of hemodilution on peripheral resistance,
      whole body oxygen delivery, and oxygen consumption was determined over a range of
      hematocrit values. METHODS: Measurements were obtained during 38 degrees C
      cardiopulmonary bypass with progressive normovolemic hemodilution (hematocrit
      value 40% to 9%) in nine dogs. Dextran 70 (6%) was used as a diluent. Anesthesia
      consisted of high-dose fentanyl and midazolam. A mean arterial pressure of 60 mm
      Hg was maintained throughout cardiopulmonary bypass via increases in pump flow.
      RESULTS: Progressive hemodilution was associated with a decreasing total
      peripheral resistance. During normothermic cardiopulmonary bypass with a whole
      blood prime, the whole body oxygen consumption approximated values previously
      reported in dogs under nonbypass conditions. Oxygen delivery and whole body
      oxygen uptake were maintained between a hematocrit value of 39% and 25%.
      Significant decreases for both were seen when the hematocrit value was reduced to
      18% and below. CONCLUSIONS: A hematocrit level greater than 18% was needed to
      maintain systemic oxygen delivery and consumption during warm cardiopulmonary
      bypass. The critical hematocrit value may be higher under bypass than nonbypass
      conditions because the flow increases that are practical during cardiopulmonary
      bypass do not approximate those seen in response to hemodilution of the intact
      circulation. Finally, the critical hematocrit value for the body may be higher
      than that required for the brain during warm cardiopulmonary bypass.

PMID- 9605093
TI  - Reversal of iatrogenic myocardial edema and related abnormalities of diastolic
      properties in the pig left ventricle.
AB  - OBJECTIVE: This study examines the resolution of iatrogenic edema and related
      changes in systolic and diastolic properties in the intact pig left ventricle.
      METHODS: The coronary arteries were perfused for 50 to 60 seconds with diluted
      blood (hematocrit value 10% +/- 1%, edema group, n = 5) or whole blood
      (hematocrit value 28% +/- 1%, control group, n = 6) infused into the aortic root
      during aortic crossclamping in conditioned, anesthetized pigs. After whole blood
      reperfusion, preload reduction by vena caval occlusion was used to define
      systolic and diastolic properties at 15-minute intervals. Left ventricular
      pressure and conductance, aortic flow, and two-dimensional echocardiography were
      recorded. RESULTS: Left ventricular mass (wall volume) in the edema group
      increased significantly compared with that in control pigs after crossclamp
      removal. Mass returned to preperfusion levels after 45 minutes. The ventricular
      stiffness constant (beta) increased significantly in the edema group versus the
      control group, returning to baseline by 30 minutes. The diastolic relaxation
      constant (tau) and base constant (alpha) did not differ between groups. There was
      no significant change in contractility. CONCLUSION: Increases in left ventricular
      mass and diastolic stiffness induced by coronary perfusion with hemodiluted blood
      resolve after 45 minutes of whole blood perfusion in pigs. This study defines
      physiologic effects of edema in the normal heart while eliminating most common
      confounding experimental errors.

PMID- 9605094
TI  - Echocardiographic and surgical correlation of pericardial effusions in patients
      with malignant disease.

PMID- 9605096
TI  - Long-term survival after resection of a mediastinal metastasis from a renal cell
      carcinoma.

PMID- 9605095
TI  - Successful esophageal tracheobronchoplasty for combined tracheal and bronchial
      traumatic rupture.

PMID- 9605097
TI  - Aortic valve-preserving procedure for enlargement of the left ventricular outflow
      tract and mitral anulus.

PMID- 9605098
TI  - Inverted left atrial appendage.

PMID- 9605099
TI  - Is cervical involvement a sign of incurable disease in cancer of the thoracic
      esophagus?

PMID- 9605100
TI  - Interruption of normothermic cardioplegia and its effects on myocardial
      preservation.

PMID- 9605101
TI  - Bleeding reduction in cardiac surgery: a combined approach.

PMID- 9605102
TI  - Whither goes the alveolar macrophage? Another small chapter is written on the
      localized response of this crucial cell.

PMID- 9605103
TI  - Assessment of the hepatic circulation in humans: new concepts based on evidence
      derived from a D-sorbitol clearance method.
AB  - D-Sorbitol (SOR) is safe, is easy to measure, and has an exceptionally high
      extraction ratio in the normal liver of 0.93+/-0.05 (mean+/-SD). Together with
      the general interest in hepatic hemodynamics, these facts motivated us to review
      the usefulness of this compound for the assessment of liver plasma flow in
      humans. We concluded that in subjects without liver disease the nonrenal
      clearance of SOR-measured noninvasively-very closely approximates hepatic plasma
      flow. Because of its lower and more variable extraction ratio, indocyanine green
      should no longer be used without hepatic vein catheterization. Even in patients
      with cirrhosis, SOR exhibits higher hepatic extraction ratios than indocyanine
      green. To fully explore the potential of SOR in the evaluation of such patients
      attention needs to be paid to the complex changes in architecture and function
      occurring in this disease. In cirrhotics the noninvasively measured nonrenal
      clearance of SOR presumably approximates the flow through intact and capillarized
      sinusoids (functional flow) and reflects the amount of blood having functional
      contact with hepatocytes. The theoretic background of the method, its accuracy,
      further research needs, and potentials of various approaches are discussed in
      detail.

PMID- 9605104
TI  - Markers and determinants of progression of HIV-1 infection.

PMID- 9605105
TI  - Apoptosis induction in synovial fibroblasts by ceramide: in vitro and in vivo
      effects.
AB  - Several lipid second messengers are important mediators of extracellular signals.
      Among them ceramide, which is formed by cell membrane sphingomyelin, influences
      the apoptotic signal pathway through Fas antigen. We examined the apoptotic
      effect of cell-permeable C2-ceramide on rheumatoid synovial fibroblasts in vitro
      and in vivo. Exposure of cultured human rheumatoid synovial fibroblasts to C2
      ceramide for 24 hours produced internucleosomal DNA fragmentation and morphologic
      changes characteristic of apoptosis. This C2-ceramide-mediated apoptosis was dose
      dependent as confirmed by analysis of cytosolic oligonucleosome-bound DNA of
      treated synovial fibroblasts. We also demonstrated that intra-articular
      administration of C2-ceramide into Fas-deficient MRL lpr/lpr mice produced a
      profound reduction of synovial hyperplasia within 24 hours. In situ nick end
      labeling analysis confirmed the induction of apoptosis in synovial lining cells.
      Our results indicate that C2-ceramide may function as a potent inducer of
      apoptosis in the synovium and suggest that pharmacologically-induced apoptosis
      may be useful as a new therapeutic modality for rheumatoid arthritis.

PMID- 9605106
TI  - Chemotaxis of alveolar macrophages in response to signals derived from alveolar
      epithelial cells.
AB  - We have postulated that alveolar epithelial cells (AEC) play a critical role in
      local regulation of alveolar macrophage (AM) recruitment and activation for host
      defense in the lung. The present study explores the effects of conditioned medium
      from AEC (AEC-CM) on the migration of AM, using a Boyden chamber assay. AEC-CM
      was chemotactic for AM, with peak activity observed with a 1:10 dilution. We
      previously showed that rat AEC express the chemokines RANTES (regulated on
      activation, normal T expressed and secreted) and monocyte chemoattractant protein
      1 (MCP-1) as well as granulocyte-macrophage colony-stimulating factor (GM-CSF).
      Neutralizing antibodies to RANTES and to MCP-1 and immunoprecipitation of GM-CSF
      decreased the chemotactic activity of AEC-CM by 58%, 29%, and 47%, respectively.
      Similar levels of chemotaxis were found in response to recombinant RANTES, MCP-1,
      and GM-CSF. In each instance the optimal dose was very low (0.01 to 0.1 ng/ml),
      with diminished chemotaxis at higher doses. Peritoneal macrophages (PM) also
      migrated in response to AEC-CM and each of the recombinant cytokines; however, AM
      were much more sensitive to AEC-CM, RANTES, and GM-CSF than were PM. AM migrated
      preferentially from medium conditioned by unstimulated AEC toward supernatants
      from interleukin 1alpha-stimulated AEC. Therefore, AEC may control the
      distribution of AM through the creation of local chemotactic gradients and are
      likely to play a critical role in the host response to low-level antigen entry
      into the peripheral lung.

PMID- 9605107
TI  - Essential carbamoyl-amino acids formed in vivo in patients with end-stage renal
      disease managed by continuous ambulatory peritoneal dialysis: isolation,
      identification, and quantitation.
AB  - Carbamoyl-amino acids (C-AA) are formed by reaction of amino acids with cyanate,
      which is spontaneously formed from urea at body temperature and pH. In vivo
      derivatized C-AA are not measured by the usual amino acid analysis methods, which
      require a free amino group for derivatization. Free-amino acids (F-AA) but no C
      AA were found in the postabsorptive plasma of eight normal persons with blood
      urea nitrogen (BUN) levels ranging from 9 to 16 mg/dl. In a longitudinal study of
      postprandial plasma (n=43), essential amino acids, both C-AA and F-AA, were
      isolated and quantified by reverse-phase high-pressure liquid chromatography in
      six patients with end-stage renal disease who were managed by continuous
      ambulatory peritoneal dialysis. The mean BUN was 61 mg/dl (range, 36 to 79
      mg/dl). In uremia, removal of F-AA from the essential amino acid pool to form C
      AA is measured by the ratio of C-AA to F-AA (carbamoylation index (CI)). Using
      the mean value for each essential amino acid, the CIs were as follows: leucine,
      4; valine, 3.3; isoleucine, 11.4; threonine, 9; lysine, 2; methionine, 3.5;
      histidine, 3.5; phenylalanine, 0.5; and tyrosine, 1.3. Carbamoylation of F-AA may
      account, in part, for the lower than normal levels of F-AA in patients with
      uremia. The derivatized amino group of C-AA interferes with formation of a
      peptide bond in protein synthesis, which requires an underivatized amino acid. A
      decrease in the F-AA pool available for protein synthesis and anabolism in the
      presence of C-AA may provide additional contributing factors for the development
      of malnutrition in uremia.

PMID- 9605108
TI  - Hepatic inflammatory responses to alphaalpha-cross-linked hemoglobin infusion in
      rats.
AB  - Cross-linked hemoglobin (alphaalpha-Hb) may be a useful red blood cell substitute
      if it can be administered safely. However, cell-free hemoglobin has inherent
      properties that may cause oxidant-mediated toxicity. We investigated whether
      alphaalpha-Hb induces oxidative or inflammatory responses that lead to liver
      damage. alphaalpha-Hb (0.5 or 1.0 gm/kg) was infused into rats, and indices of
      liver injury, inflammation, and oxidative stress were examined. Although focal
      hepatic necrosis was noted at 24 hours, plasma alanine aminotransferase activity
      was not increased and lesions were resolved by 48 hours. Modest neutrophil
      accumulation in hepatic vessels, but not sinusoids, occurred at 24 hours. Heme
      oxygenase-1 (HO-1) protein and activity were induced in a dose- and time
      dependent manner, with maximal induction at 24 hours. Plasma tumor necrosis
      factor-alpha levels were not significantly increased. Additional cytokine- and
      oxidant-mediated events such as nuclear transcription factor-kappaB activation
      and nitric oxide synthase induction were not observed. These results suggest that
      alphaalpha-Hb-derived products such as heme and ferric iron (Fe3+), potent
      inducers of HO-1, are responsible for increasing HO-1. HO-1 induction may be a
      protective response by the liver to metabolize excess heme and Fe3+, thereby
      providing antioxidative products to counter the potentially damaging oxidants
      produced by Fe3+-catalyzed reactions.

PMID- 9605109
TI  - Chronic ethanol administration causes oxidative stress in the rat pancreas.
AB  - There is increasing evidence implicating oxidative stress in the pathogenesis of
      both acute and chronic pancreatitis. Because ethanol is a major cause of
      pancreatitis in Western society, the aim of this study was to determine whether
      chronic ethanol administration results in oxidative stress in the pancreas.
      Twelve pairs of rats were fed a diet containing ethanol as 36% of calories or an
      isocaloric control diet for 4 weeks. Ethanol feeding resulted in a 46% increase
      in pancreatic malondialdehyde (p=0.006). In addition, total pancreatic
      glutathione was increased by 22% (p=0.005). These biochemical changes occurred in
      the absence of histologic evidence of inflammation or necrosis, implying that the
      observed oxidative stress is a primary phenomenon rather than part of an
      inflammatory response.

PMID- 9605110
TI  - Beneficial effects of chronic administration of dietary omega-3 polyunsaturated
      fatty acids in dogs with renal insufficiency.
AB  - Dietary supplementation with polyunsaturated fatty acids (PUFA) alters the course
      of experimental renal disease in rats. However, chronic renal disease in other
      laboratory animals and in human beings frequently responds differently to
      experimental manipulations. We investigated the effects of variations in dietary
      PUFA composition on the chronic course of induced renal disease in dogs. Two
      months after 15/16 nephrectomy, dogs were randomly divided into three groups of
      seven animals each. For the next 20 months, each group of dogs was fed a low-fat
      basal diet supplemented with one of three sources of lipid to achieve a final
      concentration of 15% added fat. Fat sources provided omega-3 PUFA (menhaden fish
      oil, group FO), omega-6 PUFA (safflower oil, group SO), or saturated fatty acids
      (beef tallow, group BT). Throughout the dietary trial, the magnitude of
      proteinuria and the plasma concentrations of creatinine, cholesterol, and
      triglyceride were lower in group FO. The mean overall glomerular filtration rate
      was 0.89+/-0.18 ml/min per kilogram of body weight in group SO, a value that was
      significantly less (p < 0.05) than the corresponding values for groups BT and FO
      (1.21+/-0.18 and 1.43+/-0.20 ml/min/kg, respectively). Renal interstitial
      fibrosis also was significantly elevated in group SO. The extents of mesangial
      matrix expansion, glomerulosclerosis, and renal interstitial cellular infiltrate
      were similar in groups BT and SO, but lower (p < 0.05) in group FO. We conclude
      that supplementation with omega-6 PUFA enhanced renal injury; supplementation
      with omega-3 PUFA was renoprotective.

PMID- 9605111
TI  - Atherogenic lipoproteins enhance mesangial cell expression of platelet-derived
      growth factor: role of protein tyrosine kinase and cyclic AMP-dependent protein
      kinase A.
AB  - Mesangial cell proliferation and extracellular matrix accumulation are
      fundamental in the pathogenesis of glomerulosclerosis. Platelet-derived growth
      factor (PDGF) is a major cytokine involved in mesangial cell proliferation, and
      its increased expression is seen in glomerular injury. Atherogenic lipoproteins
      stimulate mesangial cell proliferation and induce glomerular injury in
      experimental animals. We examined the effect of low-density lipoprotein (LDL) and
      its more atherogenic oxidized forms, minimally modified LDL (mm-LDL) and oxidized
      LDL (ox-LDL) on mesangial cell PDGF mRNA expression. Incubation with 2.5 to 25
      microg/ml LDL or mm-LDL for 1 to 4 hours stimulated mesangial cell PDGF mRNA
      expression (mm-LDL 2 to 3 times greater than LDL); ox-LDL had no effect.
      Similarly, both LDL and mm-LDL induced mesangial cell DNA synthesis (mm-LDL 1.5
      to 2 times greater). In further studies evaluating key associated intracellular
      signal transduction mechanisms, the protein tyrosine kinase (PTK) inhibitors
      herbimycin and genistein markedly decreased basal and lipoprotein-induced PDGF
      mRNA expression. Both pertussis toxin and isoproterenol, cyclic AMP-generating
      substances, stimulated PDGF mRNA expression. Preincubation with H-8 or H-89,
      cyclic AMP-dependent protein kinase A (PKA) inhibitors, blocked the lipoprotein
      induced PDGF message, whereas preincubation with calphostin C, a protein kinase C
      inhibitor, did not alter LDL- or mm-LDL-mediated PDGF mRNA expression. These data
      suggest that the accumulation of atherogenic lipoproteins and their endogenous
      oxidized forms within the glomerulus may regulate mesangial cell PDGF expression
      and related cellular responses. These events appear to be modulated by signal
      transduction pathways involving PTK and PKA.

PMID- 9605112
TI  - Mitochondrial respiratory enzymes are a major target of iron toxicity in rat
      heart cells.
AB  - Our previous studies in iron-loaded rat heart cells showed that in vitro iron
      loading results in peroxidative injury, manifested in a marked decrease in rate
      and amplitude of heart cell contractility and rhythmicity, which is correctable
      by treatment with deferoxamine (DF). In the present studies we explored the role
      of mitochondrial damage in myocardial iron toxicity. Iron loading by 24-hour
      incubation with 0.36 mmol/L ferric ammonium citrate resulted in a decrease in the
      activity of nicotinamide adenine dinucleotide (NADH)-cytochrome c oxidoreductase
      (complex I+III) to 35.3%+/-11.2% of the value in untreated controls; of succinate
      cytochrome c oxidoreductase (complex II+III) to 57.4%+/-3.1%; and of succinate
      dehydrogenase to 63.5%+/-12.6% (p < 0.001 in all cases). The decrease in activity
      of other mitochondrial enzymes, including NADH-ferricyanide reductase, succinate
      ubiquinone oxidoreductase (complex II), cytochrome c oxidase (complex IV), and
      ubiquinol cytochrome c oxidoreductase (complex III), was less impressive and
      ranged from 71.5%+/-15.8% to 91.5%+/-14.6% of controls. That the observed loss of
      respiratory enzyme activity was a specific effect of iron toxicity was clearly
      demonstrated by the complete restoration of enzyme activities by in vitro iron
      chelation therapy. Sequential treatment with iron and doxorubicin caused a loss
      of complex I+III and complex II+III activity that was greater than that seen with
      either agent alone but was only partially correctable by DF treatment.
      Alterations in cellular adenosine triphosphate measurements paralleled very
      closely the changes observed in respiratory complex activity. These findings
      demonstrate for the first time the impairment of cardiac mitochondrial
      respiratory enzyme activity caused by iron loading at conditions formerly shown
      to produce severe abnormalities in contractility and rhythmicity.

PMID- 9605113
TI  - Valve disease associated with chronic intake of fenfluramines.

PMID- 9605114
TI  - Cutting edge: signals from the B lymphocyte antigen receptor regulate MHC class
      II containing late endosomes.
AB  - The B lymphocyte response to protein Ag is dependent upon the successful
      presentation to T cells of Ag-derived, MHC class II-restricted peptides. The B
      cell Ag receptor (BCR) facilitates this process by internalizing ligand and
      delivering it to specialized compartment(s) (MHC class II peptide-loading
      compartments (MIIC)) where it is processed into peptides and loaded onto MHC
      class II. In addition to efficiently targeting Ag, the BCR can provide tyrosine
      kinase-dependent signals that augment the presentation of Ag, possibly by
      enhancing the generation of immunogenic peptides. However, the mechanism by which
      this occurs is unclear. Herein, we report that the BCR signals a reorganization,
      fusion, and acidification of an MHC-like compartment into an invariant chain- and
      MHC class II-rich complex of large vesicles. This complex becomes the primary
      target for endocytosed receptors. These data suggest that signals generated by
      the BCR regulate the site of Ag processing.

PMID- 9605115
TI  - Cutting edge: novel RNA ligands able to bind CD4 antigen and inhibit CD4+ T
      lymphocyte function.
AB  - The value of high affinity-specific reagents in immunology is exemplified by the
      use of mAbs. Recent in vitro selection methods suggested that oligonucleotides
      may provide a useful alternative, especially where Abs have been insufficient
      thus far. We used a systematic evolution of ligands by exponential enrichment
      (SELEX) procedure to derive high affinity oligonucleotide ligands (aptamers)
      recognizing CD4. These RNase-resistant aptamers bound with high affinity and
      specificity as demonstrated using BIAcore (Stevenage, U.K.) technology. They also
      bound native CD4 on rat lymphocytes and specifically interfered with labeling by
      high affinity mAbs. All aptamers recognized the same binding site in the CDR2
      like region in domain 1 of CD4. The applicability of these aptamers for
      immunologic studies was clearly demonstrated by their ability to block a fully
      allogeneic MLR in a CD4-specific manner. The high affinity and stability of
      aptamers point to their value in the analysis and functional manipulation of the
      immune system.

PMID- 9605116
TI  - Adenovirus-mediated transfer of viral IL-10 gene inhibits murine collagen-induced
      arthritis.
AB  - IL-10 is a potent anti-inflammatory cytokine that has received growing attention
      for its therapeutic potential. We examined the efficiency of adenoviral-mediated
      gene transfer of IL-10 on the incidence and severity of murine collagen-induced
      arthritis (CIA). Male DBA1 mice immunized with collagen II were treated by
      systemic administration of 10(9) plaque-forming units of replication-defective
      adenoviral vector expressing viral IL-10 (vIL-10) on day 30, when clinical
      symptoms of arthritis start. The transgene was shown to inhibit the onset of CIA,
      to decrease severity, and profoundly suppress the overall joint histopathology of
      the experimental arthritis. Significant IL-10 concentrations were obtained in the
      serum of injected animals for 7 days. Inhibition of arthritis was enhanced by
      administration of increasing doses of adenovirus-vIL-10. In addition, the local
      immunosuppressive effect of gene-delivered vIL-10 could be neutralized by a
      monoclonal anti-vIL-10 Ab. The CIA symptoms in the group treated with the same
      construct expressing inactive vIL-10 (vIL-10 mut) were similar to those in
      untreated animals. Our data indicate that a single systemic administration of an
      adenoviral vector encoding vIL-10 may be a good candidate to suppress arthritis.

PMID- 9605117
TI  - Early preferential stimulation of gamma delta T cells by TNF-alpha.
AB  - Although recent findings indicate that gamma delta T cells influence both early
      innate and Ag-specific adaptive host responses, it has remained unclear what
      triggers gamma delta T cell reactivity. Investigating very early T cell
      activation in mouse and human models of bacterial infection, we measured CD69
      expression as an indicator of early cellular activation. Both murine alpha beta
      and gamma delta T cells responded polyclonally to systemic bacterial infections,
      and to LPS. However, gamma delta T cells responded more strongly to the bacteria
      and to LPS. In vitro LPS-stimulated human T cells showed a similar differential
      response pattern. We identified TNF-alpha as mediator of the early differential T
      cell activation, and of differential proliferative responses. The stronger
      response of gamma delta T cells to TNF-alpha was correlated with higher inducible
      expression levels of TNF-Rp75. Among unstimulated splenocytes, more gamma delta T
      cells than alpha beta T cells expressed CD44 at high levels. The data suggest
      that TNF-Rp75 determines the differential T cell reactivity, and that most gamma
      delta T cells in the normal spleen are present in a presensitized state. As TNF
      alpha stimulates activated T cells, it may early preferentially connect gamma
      delta T cell functions with those of cells that produce this cytokine, including
      activated innate effector cells and Ag-stimulated T lymphocytes.

PMID- 9605119
TI  - Killer cell inhibitory receptors for MHC class I molecules regulate lysis of
      melanoma cells mediated by NK cells, gamma delta T cells, and antigen-specific
      CTL.
AB  - NK cells and T cells express killer cell inhibitory receptors (KIR) recognizing
      polymorphic MHC class I molecules. Although prior studies have established that
      MHC class I can protect normal and transformed hematopoietic cells from NK cell
      lysis, the role of MHC class I on the recognition of solid tumors has been
      controversial. In this study, we investigated whether interactions of KIR with
      their ligands on melanoma tumor cells could inhibit tumor cell lysis by NK and
      gamma delta T cell clones. Ligation of the NK cell receptor KIR3DL1 by HLA-Bw4
      allotypes resulted in inhibition of cytotoxicity against HLA-B*4403-transfected
      melanomas as well as against melanomas endogenously expressing HLA-Bw4 allotypes.
      Similarly, interactions of KIR2DL2 or KIR2DL3 (KIR2DL2/3) with HLA-Cw3-related
      allotypes on melanomas resulted in decreased tumor cell lysis. We also
      investigated whether signaling via KIR affected melanoma recognition by CTL.
      Introduction of KIR3DL1 molecules into HLA-A*0201-restricted gp100-specific CTL
      resulted in inhibition of lysis of gp100+ melanomas co-expressing HLA-A*0201 and
      HLA-Bw4 allotypes. These results suggest that disrupting interactions of KIR with
      their ligands on tumor cells in vivo may enhance antitumor responses mediated by
      both innate and adaptive immune effector cells.

PMID- 9605118
TI  - CD95 (Fas)-based, superantigen-dependent, CD4+ T cell-mediated down-regulation of
      human in vitro immunoglobulin responses.
AB  - Naturally occurring microbial superantigens (SAg) have been implicated in several
      human idiopathic disorders, and a compelling argument for the role of SAg in
      autoantibody-associated disorders, such as systemic lupus erythematosus, has been
      proposed. To test the effects of SAg on human in vitro Ig responses, CD4+ T cell
      + B cell cultures were stimulated with graded doses of staphylococcal enterotoxin
      B (SEB). Ig-secreting cell (IgSC) responses were very weak in CD4+ T cell + B
      cell cultures stimulated with SEB at the optimal mitogenic concentration (high
      dose SEB; 100 ng/ml) but were strong in parallel cultures stimulated with low
      dose SEB (0.01 ng/ml). High dose SEB actually enhanced B cell differentiation in
      the presence of CD4+ T cell soluble helper factors as long as the B cells were
      prevented from physically contacting the CD4+ T cells. However, when cell-cell
      contact between CD4+ T cells and B cells was permitted, high dose, but not low
      dose, SEB promoted increased CD4+ T cell-mediated B cell apoptosis with resulting
      decreases in viable CD20+ B cells and IgSC. High dose, but not low dose, SEB
      triggered increased levels of soluble CD95 ligand, and down-regulation of IgSC
      responses and incremental apoptosis of activated B cells were prevented by
      antagonist anti-CD95 mAb. This strongly suggests that CD4+ T cell-mediated CD95
      based killing of activated B cells plays a major role in controlling SEB-driven
      IgSC responses. Defects in SAg-based down-regulation may contribute to autoimmune
      disorders such as SLE.

PMID- 9605120
TI  - In vivo inflammatory response to a prototypic B cell superantigen: elicitation of
      an Arthus reaction by staphylococcal protein A.
AB  - Staphylococcal protein A (SpA) is representative of a new class of Ags, the B
      cell superantigens (SAgs). These SAgs, unlike conventional Ags, bind to the Fab
      regions of Ig molecules outside their complementarity-determining regions. In
      addition, B cell SAgs can react with a substantial amount of a host's serum Igs
      by virtue of their ability to interact with many members of an entire variable
      heavy chain (VH) or variable light chain gene family. For example, SpA reacts
      with the Fabs of most human Igs using heavy chains from the VH3 gene family
      (VH3+). Members of this gene family are expressed on 30 to 60% of human
      peripheral B cells. We sought to determine whether the interaction of a B cell
      SAg with its reactive Igs can elicit immune complex-mediated tissue injury. Using
      the Arthus reaction in rabbits as an in vivo model of immune complex-mediated
      tissue inflammation, we demonstrated that untreated rabbits, which were
      administered SpA intradermally (i.d.), do not develop a cutaneous inflammatory
      response. However, when rabbits were pretreated i.v. with human IgG (hIgG), i.d.
      injections of SpA induced an inflammatory response with the classical histologic
      features of an Arthus reaction. To determine whether this Arthus-like response
      occurred via a B cell superantigenic mechanism, the rabbits were pretreated with
      VH3-depleted hIgG and then were administered SpA i.d. We found that the induction
      of a prominent inflammatory response by SpA was dependent upon the presence of
      VH3+ molecules in the hIgG pretreatment. These results provide compelling
      evidence that an interaction of the B cell SAg, SpA, with its reactive (VH3+)
      IgGs leads to an immune complex-mediated inflammatory response in vivo.

PMID- 9605121
TI  - Two types of anti-TL (thymus leukemia) CTL clones with distinct target
      specificities: differences in cytotoxic mechanisms and accessory molecule
      requirements.
AB  - TCRalphabeta CTL clones recognizing mouse thymus leukemia (TL) Ags were
      established and categorized into two groups: those killing any TL+ target cells
      (type I) and those killing only TL+ Con A blasts (type II). Cold target
      inhibition assays showed that the antigenic determinant(s) recognized by type II
      clones are expressed not only on TL+ Con A blasts but also on other TL+ target
      cells. The relation of the target specificity to the killing machinery and the
      accessory molecules involved in cytotoxicity were therefore analyzed using four
      representative clones selected from each type. Of the target cells tested, Fas
      was only expressed on Con A blasts, indicating that Fas ligand (FasL)-dependent
      cytotoxicity is limited to such cells. All four type II and one of four type I
      clones expressed FasL on the surface, while both types contained perforin in the
      cytoplasm. Blocking studies using neutralizing anti-FasL mAbs and concanamycin A
      (CMA), a selective inhibitor of the perforin pathway, suggested that type I
      clones kill target cells by way of perforin, while type II clones kill TL+ Con A
      blasts through FasL together with perforin. For their cytotoxicity, type I CTLs
      require a signal through CD8, while type II require LFA-1/ICAM-1 interactions.
      Type II clones also need a co-stimulatory signal through an unknown molecule for
      perforin-dependent cytotoxicity. These results taken together suggest that the
      difference in the target specificity of anti-TL CTL clones is due to variation in
      the killing machineries and the dependence on accessory molecules.

PMID- 9605122
TI  - Generation of an MHC class II-restricted T cell epitope by extracellular
      processing of hepatitis delta antigen.
AB  - Hepatitis delta virus is a human pathogen that is responsible for a severe form
      of hepatitis affecting hepatitis B envelope Ag carriers. We have previously
      identified a series of hepatitis delta Ag (HDAg) epitopes that are recognized by
      CD4+ T cell clones isolated from infected subjects. Herein, we show that the
      presentation of soluble HDAg to CD4+ T cell clones that are specific for the
      HDAg(106-121) epitope was exceptionally unaffected by the inhibition of the APC
      processing machinery when APCs were fixed with glutaraldehyde before Ag pulsing
      or treated with chloroquine or brefeldin A. Interestingly, 5 h of pulsing was
      strictly required for the efficient presentation of the HDAg(106-21) epitope by
      fixed APCs, suggesting that some form of extracellular processing had occurred.
      Indeed, fixed APCs were able to present HDAg after only 1 h of pulsing when HDAg
      was preincubated with serum for 5 h. More important, presentation was completely
      abrogated when Ag was previously incubated in medium containing serum in the
      presence of a potent inhibitor of trypsin activity such as the secretory
      leukoprotease inhibitor. These results show that HDAg may undergo extracellular
      processing and suggest that the generation of immunogenic epitopes directly by
      serum proteases could play a role in the immune response against hepatitis delta
      virus during infection.

PMID- 9605123
TI  - Two T cell epitopes from the M5 protein of viable Streptococcus pyogenes engage
      different pathways of bacterial antigen processing in mouse macrophages.
AB  - We studied the mechanisms of MHC class II-restricted bacterial Ag processing of
      the surface fibrillar M5 protein from viable Streptococcus pyogenes in murine
      macrophages. Two previously defined T cell epitopes were studied using T cell
      hybridomas specific for 308-319/Ad, associated with the cell wall on the surface
      of streptococci, and 17-31/Ed, located at the protruding amino terminus of M5.
      Studies with metabolic inhibitors showed that slow (1 h) processing of M5 308-319
      occurred in late endosomes and was dependent on newly synthesized MHC class II
      molecules and microtubules and on communications between early and late
      endosomes, consistent with engagement of the classical MHC class II processing
      pathway. In contrast, fast (15 min) bacterial Ag processing of 17-31 occurred in
      early endosomes independently of newly synthesized MHC class II molecules and
      microtubules and of trafficking between early and late endosomes, consistent with
      the recycling MHC class II processing pathway. Finally, bacterial Ag processing
      of the epitopes exhibited differential sensitivity to blocking with anti-MHC
      class II Abs. Thus, two T cell epitopes of a single protective Ag from the
      surface of whole bacteria are routed to distinct MHC class II processing
      pathways.

PMID- 9605124
TI  - Expression of complement receptors 1 and 2 on follicular dendritic cells is
      necessary for the generation of a strong antigen-specific IgG response.
AB  - Two mechanisms could account for the impaired humoral immune response found in
      Cr2-/- mice. The absence of complement receptors 1 and 2 (CR1, CR2) on B cells
      could affect their activation. Alternatively, impaired Ag trapping by follicular
      dendritic cells (FDC) could affect B cell maturation into Ig-secreting or memory
      B cells. To compare the roles of CR1 and CR2 on B cells vs FDC in this abnormal
      response, bone marrow (BM) chimeric mice were generated and immunized with
      specific T-dependent Ags. The primary and secondary Ab response was measured.
      Cr2+/+ animals reconstituted with a Cr2-/- BM generated a diminished but
      detectable humoral immune response compared with controls. When injected with
      preformed immune complexes (IC), these mice maintained follicular IC
      localization. Cr2-/- animals reconstituted with a Cr2+/+ BM had an initial rise
      in the Ab titer, but were unable to maintain it as shown by a pronounced decrease
      in the IgG titer. This defect persisted during the secondary immune response.
      Follicular IC trapping was also impaired. Despite the abnormal Ab response,
      germinal center formation was retained in all of the chimeric animals. These
      experiments are the first to demonstrate an absolute requirement for CR1 and CR2
      expression on FDC in the generation of a normal humoral immune response.

PMID- 9605125
TI  - Generation, persistence, and modulation of Th0 effector cells: role of autocrine
      IL-4 and IFN-gamma.
AB  - Many studies have classified CD4 responses into either Th1-like or Th2-like,
      based on cytokine secretion profiles, but little significance has been placed on
      Th0 cells. This has largely resulted from studies that suggested that Th0
      populations primarily comprise individual Th1 and Th2 cells. Here, we show that
      priming of Ag-specific naive CD4 cells with moderate dose IL-4 generates a Th0
      population that is evident after 3 days in vitro and becomes prevalent after
      successive encounters with Ag over a 9-day period. By intracellular cytokine
      staining, the majority (>60%) of effector cells generated in this way produce
      either IL-4, IFN-gamma and IL-2, or IL-4 and IFN-gamma without IL-2. Endogenous
      IFN-gamma secreted over the initial 3 days of culture was critical for generating
      Th0 cells, since neutralization allowed IL-4 to induce differentiation into Th2
      like cells. Successive encounters with Ag were required for generating Th0 cells,
      and their stability and persistence were governed by the balance of endogenous IL
      4 and IFN-gamma secreted during the later stages of differentiation. Studies
      blocking Fas-induced cell death showed that this process played no role in Th0
      cell generation, and differential death of committed Th1 or Th2 cells was not
      required for Th0 persistence. These data suggest that Th0 cells can be as
      prevalent as Th1- or Th2-like cells after naive CD4 activation, that the relative
      levels of autocrine IL-4 and IFN-gamma are important to the lack of commitment,
      and that not all cells are predestined to the Th1 or Th2 phenotypes early in the
      response.

PMID- 9605126
TI  - Autocrine and paracrine apoptosis are mediated by differential regulation of Fas
      ligand activity in two distinct Jurkat T cell populations.
AB  - Fas ligand (FasL) produced by activated T cells mediates autocrine-induced
      apoptosis to limit T cell expansion. To investigate the regulation of FasL
      activity, Jurkat cells were stably transfected with a 2.3-kb fragment of human
      FasL promoter that controlled the expression of a GFP reporter gene. Two
      populations of Jurkat cells with different levels of GFP expression were
      obtained. One population constitutively expressed high levels of GFP (GFP+),
      while the other population expressed low levels of GFP (GFP-). The level of GFP
      expression in the two populations correlated with their levels of FasL
      transcription and its functional activity. Autocrine regulation of apoptosis was
      demonstrated by increased FasL activity after stimulation of GFP- cells with anti
      CD3, phorbyl myristyl acetate plus ionomycin, or Con A. Paracrine regulation of
      apoptosis was suggested by the induction of apoptosis of GFP- cells after
      coculture with unstimulated GFP+ cells. GFP+ cells exhibited a decreased
      sensitivity to FasL-mediated apoptosis compared with GFP- cells. Furthermore, the
      cell surface expression of Fas and CD4 was lower on GFP+ cells than GFP- cells,
      whereas the expression of CD45RO was higher. A decreased level of IL-2 was
      produced by GFP+ cells after phorbyl myristyl acetate and ionomycin stimulation.
      Our results indicate that a subpopulation of T cells that express low levels of
      FasL and IL-2, which are responsive to up-regulation of these molecules after
      activation, can undergo apoptosis either by suicide after activation or by a
      paracrine pathway mediated by T cells that constitutively express higher levels
      of FasL.

PMID- 9605127
TI  - Testosterone and IL-6 requirements for human C-reactive protein gene expression
      in transgenic mice.
AB  - In vitro, IL-6 is the main inducer of the human C-reactive protein (CRP) gene,
      and IL-1 and steroids can enhance this effect. However, in mice, IL-6 is
      necessary but not sufficient for induction of the human CRP transgene, and
      testosterone is required for its constitutive expression by males. To examine the
      relative contributions of testosterone and IL-6 in the regulation of CRP gene
      expression, we produced CRP-transgenic (CRPtg), IL-6-deficient (IL-6-/-) mice.
      Male CRPtg/IL-6-/- mice expressed CRP constitutively, but CRP levels were not
      increased after injection of LPS. However, acute-phase CRP levels were attained
      after injection of IL-6. In contrast, female CRPtg/IL-6-/- mice did not express
      CRP constitutively or after administration of LPS, IL-6, IL-1, or IL-6 plus IL-1.
      Like males, testosterone-treated CRPtg/IL-6-/- females expressed CRP
      constitutively, and their transgene responded to injection of IL-6. The
      endogenous acute-phase protein serum amyloid P (SAP) was expressed constitutively
      equally by male and female IL-6-/- mice, responded minimally to LPS, and did not
      respond to either IL-6 or IL-1 alone. Acute-phase levels of SAP were induced in
      IL-6-/- mice by injection of IL-6 together with IL-1 or LPS. We conclude that in
      vivo, both constitutive and IL-6-dependent acute-phase expression of the CRP
      transgene require testosterone. In contrast, testosterone is not required for
      expression of the SAP gene, which requires IL-1 plus IL-6 for acute-phase
      induction.

PMID- 9605128
TI  - Macrophages induce cellular immunity by activating Th1 cell responses and
      suppressing Th2 cell responses.
AB  - Differentiation of naive CD4+ T cells (Th0) into Th1 or Th2 cells determines
      whether antigen will raise a cellular or a humoral immune response. The
      maturation pathway chosen by the Th0 cell is often decisive for the outcome of
      disease and depends among others on the (co-)stimulatory attributes of the APC
      and the nature and abundance of cytokines provided by the APC and the
      microenvironment. In this study, we used macrophages, loaded ex vivo with
      antigen, for inciting Th0 activation and differentiation in vivo. The macrophages
      were derived from a clonal, immortalized population that both functionally and
      phenotypically expressed features characteristic of mature macrophages. Injection
      into syngeneic mice of IFN-gamma-treated, Ag-loaded macrophages induced a primary
      T cell response, indicated by the occurrence of a proliferative response in vitro
      after restimulation of splenocytes with Ag. Analysis of the accompanying cytokine
      secretion revealed high numbers of IFN-gamma-producing Th1 cells and only a few
      IL-4-secreting Th2 cells. This dominance of Th1 cells had functional
      implications, reflected in the high titer of Th1 cell-dependent IgG2 Abs and the
      absence of IgG1, characteristic of humoral immunity. Moreover, administration of
      Ag-loaded macrophages to mice with an ongoing Th1/Th2 response resulted in a
      complete suppression of IgG1 production, whereas IgG2 levels remained unaffected.
      These results demonstrate that macrophages exert APC activity in the organism,
      strongly skew primary responses to cellular immunity, and in addition suppress an
      already generated Th2-dependent humoral response, thus characterizing these cells
      as Th1-oriented APC.

PMID- 9605129
TI  - Perforin and IFN-gamma are involved in the antitumor effects of antibody-targeted
      superantigens.
AB  - The bacterial superantigen staphylococcal enterotoxin A (SEA) is a potent inducer
      of cytokine production and cytotoxic T cell responses. To target a T cell attack
      against tumor cells we have genetically engineered a fusion protein of SEA and
      the Fab part of the tumor-reactive mAb C215. Injection of this Fab-SEA fusion
      protein to mice carrying lung metastases of the poorly immunogenic B16 melanoma
      transfected with the C215 Ag resulted in infiltration of cytokine-producing T
      cells, perforin-containing CTL, and a marked tumor elimination. Fab-SEA therapy
      induced substantial levels of IFN-gamma and TNF-alpha in serum. In the present
      study we have characterized the molecular mechanisms of the antitumor effect
      induced by Fab-SEA treatment in vivo. Neutralization of cytokines by specific Abs
      demonstrated a major role for IFN-gamma in the suppression of tumor growth. In
      addition, a minor contribution of TNF-alpha was recorded. Injections of Fab-SEA
      into normal mice induced strong CTL activity but failed to promote cytotoxic
      function in perforin knockout mice. Also, a markedly reduced therapy was noted in
      perforin knockout mice, implicating a role for CTL in Fab-SEA-mediated tumor
      eradication. The data suggest that Fab-SEA-targeted T cells may suppress tumor
      growth by both perforin-dependent cytotoxicity and local release of cytokines
      such as IFN-gamma. The latter mechanism may have an important role in cytostatic
      effects against Ag-negative bystander tumor cells.

PMID- 9605130
TI  - 1,25-dihydroxyvitamin D3 is a positive regulator for the two anti
      encephalitogenic cytokines TGF-beta 1 and IL-4.
AB  - Previously we demonstrated that 1,25-dihydroxyvitamin D3 blocks the progression
      of relapsing encephalomyelitis. We now propose that 1,25-dihydroxyvitamin D3
      blocks these autoimmune symptoms by stimulating the differentiation and/or
      function of cells that inhibit the encephalitogenic process. To support this
      belief, we have found that 1,25-dihydroxyvitamin D3 administration to mice
      increases IL-4 transcripts by 3- to 25-fold and TGF-beta 1 transcripts by 4- to
      24-fold. Similarly, IL-4 and TGF-beta 1 transcripts were higher in the central
      nervous system of 1,25-dihydroxyvitamin D3-treated mice compared with controls.
      The number of cells recoverable from the lymph nodes of 1,25-dihydroxyvitamin D3
      treated mice was only 50% that of controls. Overall, 1,25-dihydroxyvitamin D3
      treatment causes a net loss in the total number of lymphocytes while the number
      of IL-4 and TGF-beta 1 transcripts increased. The systemic and local increase in
      the expression of these two anti-inflammatory cytokines by 1,25-dihydroxyvitamin
      D3 may be responsible for the ability of this drug to block encephalomyelitis.

PMID- 9605131
TI  - Central nervous system microglial cell activation and proliferation follows
      direct interaction with tissue-infiltrating T cell blasts.
AB  - Central nervous system (CNS)-resident macrophages (microglia) normally express
      negligible or low level MHC class II, but this is up-regulated in graft-vs-host
      disease (GvHD), in which a sparse CNS T cell infiltrate is observed. Relative to
      microglia from the normal CNS, those from the GvHD-affected CNS exhibited a 5
      fold up-regulation of characteristically low CD45, MHC class II expression was
      increased 10- to 20-fold, and microglial cell recoveries were enhanced
      substantially. Immunohistologic analysis revealed CD4+ alphabetaTCR+CD2+ T cells
      scattered infrequently throughout the CNS parenchyme, 90% of which were blast
      cells of donor origin. An unusual clustering of activated microglia expressing
      strongly enhanced levels of CD11b/c and MHC class II was a feature of the GvHD
      affected CNS, and despite the paucity of T lymphocytes present, activated
      microglial cell clusters were invariably intimately associated with these T
      cells. Moreover, 70% of T cells in the CNS were associated with single or
      clustered MHC class II+ microglia, and interacting cells were predominantly deep
      within the tissue parenchyme. Approximately 3.7% of the microglia that were
      freshly isolated from the GvHD-affected CNS were cycling, and proliferating cell
      nuclear Ag-positive microglia were detected in situ. Microglia from GvHD-affected
      animals sorted to purity by flow cytometry and cultured, extended long complex
      processes, exhibited spineous processes, and were phagocytic and highly motile.
      These outcomes are consistent with direct tissue macrophage-T cell interactions
      in situ that lead to activation, proliferation, and expansion of the responding
      tissue-resident cell.

PMID- 9605132
TI  - Topical FK506 suppresses cytokine and costimulatory molecule expression in
      epidermal and local draining lymph node cells during primary skin immune
      responses.
AB  - Recently, it has been shown that the immunosuppressive macrolide lactone, FK506,
      exerts good therapeutic efficacy in inflammatory skin diseases. The aim of this
      study was to analyze the influence of topical FK506 on molecular (IL-1alpha, IL
      1beta, IL-2, IL-4, IL-12 p35, IL-12 p40, macrophage inflammatory protein-2 (MIP
      2), granulocyte-macrophage CSF (GM-CSF), TNF-alpha, and IFN-gamma) and cellular
      (I-A+/CD80+, I-A+/CD54+, I-A+/CD69+, I-A+/B220+, and CD4+/CD25+) events in
      epidermal (EC) and local draining lymph node (LNC) cells during primary contact
      hypersensitivity responses. Cytokine mRNA levels for IL-1alpha, IL-1beta, GM-CSF,
      TNF-alpha, MIP-2, and IFN-gamma in EC and for IL-2, IL-4, IL-12 p35, IL-12 p40,
      and IFN-gamma in LNC were increased and resulted in significant LNC proliferation
      during oxazolone-induced contact hypersensitivity. Topical FK506 treatment dose
      dependently suppressed oxazolone-induced LNC proliferation. This effect was
      correlated with decreased IL-1alpha, IL-1beta, GM-CSF, TNF-alpha, MIP-2, and IFN
      gamma mRNA expression within the epidermis and decreased IL-12 p35 and p40 mRNA
      expression in LNC. Further analysis of the LNC cytokine pattern revealed that the
      production of both Thl (IFN-gamma and IL-2) and Th2 (IL-4) cytokines was
      dramatically impaired after topical FK506 treatment. Flow cytometric analysis
      showed that topical FK506 decreased the population of epidermis-infiltrating CD4+
      T cells and suppressed the expression of CD54 and CD80 on I-A+ EC and LNC during
      hapten-induced contact hypersensitivity. Furthermore, topical FK506 profoundly
      impaired oxazolone-induced up-regulation of CD25 expression on CD4+ LNC and
      dramatically decreased hapten-induced expansion of I-A+/B220+ and I-A+/CD69+ LNC
      subsets. In conclusion, these results give new insights into the mechanisms of
      action of topical FK506 treatment.

PMID- 9605133
TI  - Increased threshold for TCR-mediated signaling controls self reactivity of
      intraepithelial lymphocytes.
AB  - To examine the effect of self Ag on activation requirements of TCR-alphabeta
      intestinal intraepithelial lymphocytes (IELs), we utilized the 2C transgenic (Tg)
      mouse model specific for a peptide self Ag presented by class I MHC, H-2Ld.
      CD8alpha alpha and CD4-CD8- IELs from syngeneic (H-2b, self Ag-) and self Ag
      bearing (H-2b/d, self Ag+) strains were examined for their ability to respond in
      vitro to P815 (H-2d) cell lines expressing the endogenous antigenic peptide,
      p2Ca. Proliferation, cytokine production, and CTL activity were elicited in IEL T
      cells isolated from self Ag- H-2b mice when stimulated with P815 cells expressing
      basal levels of self Ag. These responses were enhanced following the addition of
      exogenous p2Ca peptide and ectopic expression of the costimulatory molecule, B7
      1. By comparison, IEL from self Ag-bearing mice failed to respond to basal levels
      of self Ag presented by P815 cells even in the presence of B7-1-mediated
      costimulation. However, the addition of increasing amounts of exogenous p2Ca
      peptide induced a response from the in vivo "tolerized" T cells. These results
      suggest that exposure to self Ag in vivo increased the threshold of TCR
      activation of Ag-exposed self-reactive IELs. The dependence of increased signal 1
      to activate self-reactive IELs suggests a defect in TCR signaling that may
      maintain self tolerance in vivo. These data suggest that conditions that overcome
      signal 1 IEL defects may initiate autoreactive responses in the intestine.

PMID- 9605134
TI  - Alternative metabolic states in murine macrophages reflected by the nitric oxide
      synthase/arginase balance: competitive regulation by CD4+ T cells correlates with
      Th1/Th2 phenotype.
AB  - Activated murine macrophages metabolize L-arginine via two main pathways that are
      catalyzed by the inducible enzymes nitric oxide synthase (iNOS) and arginase. We
      have previously shown that CD4+ T cell-derived cytokines regulate a competitive
      balance in the expression of both enzymes in macrophages; Thl-type cytokines
      induce iNOS while they inhibit arginase, whereas the reverse is the case for Th2
      type cytokines. Here we addressed the regulation of both metabolic pathways by
      CD4+ T cells directly. Macrophages were used as APCs for established Th1 and Th2
      T cell clones as well as for in vitro polarized Th1 or Th2 T cells of transgenic
      mice bearing an MHC class II-restricted TCR. Both systems revealed a similar
      dichotomy in the macrophages; Th1 T cells led to an exclusive induction of iNOS,
      whereas Th2 T cells up-regulated arginase without inducing iNOS. Arginase levels
      induced by Th2 T cells far exceeded those inducible by individual Th2 cytokines.
      Similarly, high arginase levels could be induced by supernatants of Th2 cells
      stimulated in various ways. Ab blocking experiments revealed the critical
      importance of IL-4 and IL-10 for arginase up-regulation. Finally, strong
      synergistic effects between IL-4/IL-13 and IL-10 were observed, sufficient to
      account for the extraordinarily high arginase activity induced by Th2 cells. Our
      results suggest that the iNOS/arginase balance in macrophages is competitively
      regulated in the context of Th1- vs Th2-driven immune reactions, most likely by
      cytokines without the requirement for direct cell interaction.

PMID- 9605135
TI  - Rapamycin inhibits the generation of graft-versus-host disease- and graft-versus
      leukemia-causing T cells by interfering with the production of Th1 or Th1
      cytotoxic cytokines.
AB  - Rapamycin (RAPA), an inhibitor of cytokine responses, is under investigation in
      humans for graft-vs-host disease (GVHD) prevention. The mechanisms responsible
      for GVHD prevention are unknown. We show that RAPA is more effective in
      inhibiting CD8+ or TCR gammadelta+ than CD4+ T cell-mediated murine GVHD. To
      determine how RAPA inhibited GVHD, thoracic duct lymphocytes (TDL) were isolated
      from recipients of allogeneic donor grafts. Compared with controls, RAPA-treated
      recipients had a marked decrease in donor TDL T cell number between days 5 and 24
      posttransplant. CD8+ T cell expansion was preferentially inhibited. RAPA
      inhibited Th1 or Th1 cytotoxic (Tc1) cytokines, but not Th2 or Tc2, cell
      generation. In situ mRNA hybridization also showed that TDL T cells from RAPA
      treated mice had a lower frequency of granzyme B+ cells, indicating that RAPA
      inhibited the generation of CTL capable of mediating cytolysis through the
      release of granzyme B. In another system, RAPA was found to inhibit the GVL
      response of delayed donor lymphocyte infusions. Since CD8+ T cells are the
      primary effectors in this system, these data suggest that RAPA directly
      interfered with GVL effector cell expansion or function. We conclude that RAPA is
      effective in inhibiting Th1 or Tc1 cytokine production and CD8+ and
      TCRgammadelta+ T cell-mediated GVHD, but abrogates GVL.

PMID- 9605136
TI  - Regulation of cell morphology in B lymphocytes by IL-4: evidence for induced
      cytoskeletal changes.
AB  - Lymphocyte activation is often accompanied by changes in cell morphology, for
      example, in cell adhesion or motility. IL-4 is a cytokine exerting many effects
      on B lymphocytes. In this study, we show that stimulation with LPS in combination
      with IL-4, but not LPS or IL-4 alone, results in a pronounced dendritic
      morphology of B cells. Using a culture system in which Abs directed to B cell
      surface markers are immobilized on the tissue culture plastic, we find that cell
      spreading can be mediated by a variety of Abs, including anti-CD44, -CD23, -LFA
      1, -VLA-4, -ICAM-1, and -Ig. B cells stimulated with anti-Ig Abs plus IL-4, or
      anti-CD40 Abs in the presence or absence of IL-4, are also induced to spread,
      while IL-2, IL-5, or IL-10 in combination with LPS or alone fail to induce this.
      Spreading correlates with induction of tight cell aggregation. It is sensitive to
      cytochalasin B, indicating a requirement for intact actin cytoskeleton. CD44 is
      selectively detected in the detergent-insoluble fraction of cell lysates prepared
      from LPS plus IL-4-stimulated B cell cultures after Ab cross-linking of CD44,
      suggesting a membrane protein-cytoskeleton interaction. Interestingly, electron
      microscopy studies reveal induction of microvilli-like structures on LPS plus IL
      4-stimulated blasts, suggesting that IL-4 can influence cell morphology on an
      ultra-structural level. In summary, our data show that stimulation with LPS plus
      IL-4 or ligation of CD40 is capable of inducing dramatic morphologic changes in
      murine B cells, which correlates with in vitro induction of strong cell adhesion.

PMID- 9605137
TI  - Overexpression of p65 and c-Jun substitutes for B7-1 costimulation by targeting
      the CD28RE within the IL-2 promoter.
AB  - The role of Rel and activation protein-1 (AP-1) in IL-2 promoter activity in B7-1
      and leukocyte function-associated Ag-3 (LFA. 3)-costimulated T cells has been
      evaluated. We demonstrate that overexpression of c-Jun but not c-Fos increases IL
      2 promoter activity in both B7-1- and LFA-3-costimulated Jurkat T cells.
      Cotransfection of both c-Jun and c-Fos substitutes for B7-1 costimulation in
      driving an activation protein-1 response element but not for the IL-2 promoter.
      Overexpression of Rel proteins demonstrated that p65-expressing Jurkat cells
      transcribed equally well a nuclear factor kappabeta reporter construct when
      costimulated with B7-1 or LFA-3, but transcription of IL-2 promoter or CD28
      response element (CD28RE)-driven reporters was superior in B7-1-costimulated
      cells. Combined expression of c-Jun and p65 induced vigorous transcription of IL
      2 promoter- and CD28RE-driven reporter constructs in both LFA-3- and B7-1
      costimulated Jurkat cells. Mutating the CD28RE but not the upstream nuclear
      factor kappabeta-binding site in the IL-2 promoter reduced B7-1-driven
      transcription >90%. The results implicates a major role of the CD28RE in the
      integration of p65/c-Jun-mediated transcription within the IL-2 promoter. We
      suggest that the transition from an autocrine LFA-3-driven immune response to a
      B7--induced paracrine immune response involves the activation of c-Jun and p65,
      which target the CD28RE region of the IL-2 promoter.

PMID- 9605138
TI  - Alloreactive T cells that do not require TCR and CD8 coengagement are present in
      naive mice and contribute to graft rejection.
AB  - Class I alloreactive CTL populations have been defined as either CD8 dependent or
      CD8 independent, based upon their ability to kill target cells in the presence of
      Ab to CD8. The CD8-dependent population uses CD8 in a coreceptor role with the
      TCR, and mutations in the class I molecule that destroy the CD8 binding site
      abrogate CTL killing, even if the target cell expresses other allelic forms of
      class I molecules with an intact binding site for CD8. The CD8-independent
      population apparently does not require CD8, as Ab to CD8 has no effect on the
      ability of these cells to kill appropriate target cells. We have isolated a third
      population of CTL that is inhibited by the addition of CD8 Ab yet can kill target
      cells that express the alloantigenic molecule incapable of binding CD8, provided
      that the target cells also express non antigenic class I molecules that contain
      an intact binding site for CD8. We refer to these cells as CD8 bystander
      dependent CTL. Many (10 of 12) of these CTL were able to kill H-2Kb-expressing
      transfectants of T2 cells, consistent with the idea that they recognize a peptide
      independent determinant that may be expressed at a high density on the cell
      surface. These CD8 bystander-dependent CTL are only readily detectable in vitro
      when spleen cells from mice primed in vivo with a skin graft are used.

PMID- 9605139
TI  - Identification of a dynamic intracellular reservoir of CD86 protein in peripheral
      blood monocytes that is not associated with the Golgi complex.
AB  - In the process of developing a cancer immunotherapy strategy, we have identified
      and characterized a novel intracellular reservoir of CD86 protein in peripheral
      blood monocytes. This observation emerged from studies aimed at using retrovirus
      vectors to genetically modify tumor cells to express the costimulatory proteins
      CD80 and CD86. Retrovirus-mediated expression of CD80 and CD86 in T
      lymphoblastoid CEM cells resulted in an unexpected intracellular focal
      concentration of both proteins in the genetically modified cells. By extending
      these studies to an analysis of CD80 and CD86 expression in PBMC, we observed
      that endogenous CD86 expression in peripheral blood monocytes also involved a
      similar intracellular focal concentration of the protein. The intracellular
      concentration of CD86 in monocytes was not due to storage within the Golgi
      apparatus, and required intact microtubules to retain structural integrity.
      Furthermore, as the intensity of CD86 fluorescence increased on monocytes as a
      function of time in vitro, the intracellular focal concentration correspondingly
      decreased. These results are consistent with antegrade CD86 transport from an
      intracellular reservoir to the cell surface membrane. In this report, we detail
      the intracellular and membrane localization studies with tumor cell lines and
      PBMC, and describe the temporal relationship between intracellular storage and
      trafficking of CD86 to the cell surface membrane in peripheral blood monocytes.
      We hypothesize that this intracellular reservoir allows rapid and sustained
      deployment of an important costimulatory molecule to the monocyte surface
      membrane during initiation and maturation of the cell-mediated immune response.

PMID- 9605140
TI  - Susceptibility and resistance to antigen-induced apoptosis in the thymus of
      transgenic mice.
AB  - Injection of TCR transgenic mice with antigenic peptide results in the deletion
      of immature thymocytes expressing the transgenic TCR. We have analyzed this
      process in mice transgenic for a TCR (F5) that recognizes a peptide from the
      influenza nucleoprotein (NP68). To determine whether deletion of immature
      thymocytes is the result of specific recognition of the antigenic peptide by the
      thymocytes or mature T cell activation, bone marrow chimeric mice were generated
      using a mixture of cells from F5 transgenic and nontransgenic mice. Injection of
      these mice with antigenic peptide leads to the preferential depletion of F5
      transgenic thymocytes, whereas nontransgenic thymocytes remain largely
      unaffected. Furthermore, exposure of F5 fetal thymic lobes to peptide leads to
      thymocyte deletion even though no mature single positive T cells are present at
      this stage. These data suggest that Ag-induced death of immature thymocytes is
      due to peptide-specific recognition, although activated mature T cells appear to
      potentiate such deletion. Further administration of antigenic peptide to F5 mice
      results in the appearance of double-positive thymocytes that are resistant to Ag
      or anti-CD3-induced apoptosis. These data suggest a change in the ability of the
      cells to signal through the TCR-CD3 complex, resembling the state of anergy
      induced in peripheral T cells following chronic exposure to Ag.

PMID- 9605141
TI  - Calreticulin and calnexin interact with different protein and glycan determinants
      during the assembly of MHC class I.
AB  - Before peptide binding, a variety of endoplasmic reticulum (ER) proteins are
      associated with class I including calnexin, TAP, calreticulin, and tapasin.
      Although the selective functions of any one of these ER proteins have been
      difficult to define, individually or in combination they perform two general
      chaperone functions for class I. They promote assembly of the class I
      heterotrimeric molecule (heavy (H) chain, beta2m, and peptide) and they retain
      incompletely assembled complexes in the ER. In this study, we present evidence
      that calreticulin clearly differs from calnexin in how it associates with class
      I. Regarding the structural basis of the association, the oligosaccharide moiety
      in the alpha1 domain and the amino acid residue at position 227 in the alpha3
      domain were both found to be critical for the interaction of class I with
      calreticulin. Interestingly, calreticulin displayed sensitivity to class I
      peptide binding even in TAP-deficient human or mouse cells. Thus, calreticulin is
      clearly more specific than calnexin in the structures and conformation of the
      class I molecule with which it can interact.

PMID- 9605142
TI  - T cells expressing receptors of different affinity for antigen ligands reveal a
      unique role for p59fyn in T cell development and optimal stimulation of T cells
      by antigen.
AB  - Signaling from the TCR involves the protein tyrosine kinase p59fyn (Fyn).
      Previous studies have shown that T cell development occurs normally in Fyn-/-
      mice. In this study, we investigated the requirement for Fyn in the development
      and function of T cells expressing either the transgenic 2C TCR, with high
      affinity for its Ag ligand, or the transgenic H-Y TCR, representative of a low
      affinity TCR. Although Fyn was not essential for positive selection of thymocytes
      expressing either the 2C or the H-Y TCR, it facilitated the down-regulation of
      the heat-stable Ag in positively selected CD4-CD8+ thymocytes in both 2C and H-Y
      mice. Negative selection of thymocytes expressing the H-Y TCR also occurs
      efficiently in Fyn-/- mice. However, in Fyn-/- mice, there was a preferential
      survival of thymocytes that expressed higher levels of the CD8 coreceptor and the
      transgenic TCR. Positively selected CD4-CD8+ thymocytes and peripheral T cells
      expressing either the 2C or the H-Y TCR differed in their requirement of Fyn for
      optimal proliferation responses to stimulation by antigenic ligands. Whereas 2C
      Fyn-/- or 2C Fyn+/+ thymocytes and peripheral T cells responded optimally to
      stimulation by the specific Ag, H-Y Fyn-/- thymocytes and peripheral T cells were
      hyporesponsive compared with Fyn+/+ cells. Significantly, in response to a
      defined low affinity ligand, both 2C Fyn-/- thymocytes and peripheral T cells
      required Fyn for optimal response to Ag stimulation. Thus, Fyn plays a role
      during thymocyte development and is required for optimal responses to low
      affinity/avidity ligands.

PMID- 9605143
TI  - Identification of the immunodominant T cell epitope of p38, a major egg antigen,
      and characterization of the epitope-specific Th responsiveness during murine
      schistosomiasis mansoni.
AB  - A recently cloned major Schistosoma mansoni egg Ag p38 induced and elicited
      strong Th1-type responsiveness in mice of H-2k haplotype. Now, we have identified
      the immunodominant T cell epitope of p38 and analyzed the dynamics of epitope
      specific Th responsiveness during murine schistosomiasis mansoni. Overlapping
      recombinant and synthetic peptides that encompassed the full-length 354 amino
      acid of p38 were tested for proliferation and cytokine production in peptide- or
      p38-sensitized mice. The immunodominant T cell epitope of p38 that elicited
      pulmonary granuloma formation was localized within peptide P4 (amino acids 235
      249). The P4-specific cytokine response of splenocytes that had been sensitized
      s.c. with p38, P4 or soluble egg Ags in IFA, or i.p. with 3000 eggs was
      predominantly as the Th1 type, with strong IL-2 and IFN-gamma, but trace amounts
      of IL-4 and IL-5 secretion. At 6.5 wk of infection, splenocytes and mesenteric
      lymph node cells responded to p38/P4 peptides with predominantly Th1-type
      responsiveness. This response did not switch to a Th2-type pattern from 8 wk
      onwards; rather, it underwent down-modulation. Moreover, the hepatic granuloma
      lymphocytes at 6.5 wk responded to p38/P4 predominantly with Th1-type cytokine
      production, indicating that they participate in early granuloma formation. From 8
      wk onwards an immune deviation to the p38-specific response was observed that was
      manifested by rising IgG1, IgE, and IgG2a Ab production as opposed to declining
      Th1- and Th2-type cytokine secretion.

PMID- 9605144
TI  - IL-12 promotes drug-induced clearance of Mycobacterium avium infection in mice.
AB  - The intracellular pathogen Mycobacterium avium is a major cause of opportunistic
      infection in AIDS patients and is difficult to manage using conventional
      chemotherapeutic approaches. In the current study, we describe a strategy for the
      treatment of M. avium in T cell-deficient hosts based on the simultaneous
      administration of antibiotics and the immunomodulatory cytokine IL-12. In
      contrast to SCID mice, which were partially resistant, animals lacking a
      functional IL-12 p40 gene were found to be highly susceptible to M. avium
      infection, suggesting that the cytokine can control bacterial growth even in
      immunodeficient mice. Indeed, rIL-12 that was injected into infected SCID mice in
      high doses caused small but significant reductions in splenic pathogen loads.
      Moreover, a lower dose of IL-12, when combined with the antimycobacterial drugs
      clarithromycin or rifabutin, induced a decrease in bacterial numbers that was
      significantly greater than that resulting from the administration of the cytokine
      or drug alone. A similar synergistic effect of IL-12 and antibiotics was seen
      when immunocompetent mice were treated with the same regimen. The activity of IL
      12 in these experiments was shown to be dependent upon the induction of
      endogenous IFN-gamma. Nevertheless, IFN-gamma itself, even when given at a higher
      dose than IL-12, failed to significantly enhance antibiotic clearance of
      bacteria. Together these findings suggest that IL-12 may be a particularly potent
      adjunct for chemotherapy of M. avium infection in immunocompromised individuals
      and may result in more effective control of the pathogen without the need for
      increased drug dosage.

PMID- 9605145
TI  - IL-5-dependent immunity to microfilariae is independent of IL-4 in a mouse model
      of onchocerciasis.
AB  - Th2 lymphocyte responses under the control of IL-4 and IL-5 are frequently
      associated with protective responses to parasitic helminths. Studies on the role
      of these cytokines in acquired resistance to parasitic nematodes indicate that,
      in the case of gastrointestinal nematodes, immunity is mediated by IL-4, while
      immunity to tissue-dwelling nematodes is dependent on IL-5. Here we investigate
      the role of IL-5 and eosinophils in protective immunity to Onchocerca
      microfilariae in IL-4-deficient mice. In the absence of IL-4, and despite the up
      regulation of Th1-type responses, immunity remains dependent on IL-5 and
      eosinophils. Protection was unaffected by the absence of Ab in B cell-deficient
      mice, confirming that IL-5 is not acting via either B cell differentiation, Ag
      presentation, or isotype switching mechanisms. These data demonstrate the
      dissociation of IL-4 and IL-5 in a functional model of protective immunity to a
      tissue dwelling nematode and cast doubt on the role of IL-4 in the generation of
      CD4+ T cell-mediated, IL-5-dependent immunity to Onchocerca microfilariae.
      Importantly, they also segregate T cell-mediated mechanisms of protective
      immunity from those characterized in ocular pathologic responses in
      onchocerciasis, which are dependent on IL-4.

PMID- 9605146
TI  - Role of the hypothalamic pituitary adrenal axis and IL-6 in stress-induced
      reactivation of latent herpes simplex virus type 1.
AB  - Hyperthermic stress induces reactivation of herpes simplex virus type 1 (HSV-1)
      in latently infected mice and also stimulates corticosterone release from the
      adrenals via activation of the hypothalamic pituitary adrenal axis. In the
      present study, we tested the hypothesis that stress-induced elevation of
      corticosterone potentiates HSV-1 reactivation in latently infected mice. Because
      of the putative role of IL-6 in facilitating HSV-1 reactivation in mice, the
      effect of hyperthermic stress and cyanoketone treatment on IL-6 expression in the
      trigeminal ganglion was also measured. Preadministration of cyanoketone, a
      glucocorticoid synthesis inhibitor, blocked the stress-induced elevation of
      corticosterone in a dose-dependent manner. Furthermore, inhibition of
      corticosterone synthesis was correlated with reduced levels of HSV-1 reactivation
      in latently infected mice. Hyperthermic stress elicited a transient rise in IL-6
      mRNA levels in the trigeminal ganglion, but not other cytokine transcripts
      investigated. In addition, there was a significant reduction in MAC-3+, CD8+, and
      DX5+ (NK cell marker) cells in the trigeminal ganglion of latent HSV-1-infected
      mice 24 h after stress. Cyanoketone blocked the stress-induced rise in IL-6 mRNA
      and protein expression in the trigeminal ganglion latently infected with HSV-1.
      Collectively, the results indicate that the activation of the hypothalamic
      pituitary adrenal axis plays an important role in stimulating IL-6 expression and
      HSV-1 reactivation in the trigeminal ganglion following hyperthermic stress of
      mice.

PMID- 9605147
TI  - Fas ligand-induced apoptosis of infected human macrophages reduces the viability
      of intracellular Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis-specific cytolytic activity is mediated mostly by
      CD4+CTL in humans. CD4+CTL kill infected target cells by inducing Fas (APO
      1/CD95)-mediated apoptosis. We have examined the effect of Fas ligand (FasL)
      induced apoptosis of human macrophages infected in vitro with M. tuberculosis on
      the viability of the intracellular bacilli. Human macrophages expressed Fas and
      underwent apoptosis after incubation with soluble recombinant FasL. In
      macrophages infected either with an attenuated (H37Ra) or with a virulent (H37Rv)
      strain of M. tuberculosis, the apoptotic death of macrophages was associated with
      a substantial reduction in bacillary viability. TNF-induced apoptosis of infected
      macrophages was coupled with a similar reduction in mycobacterial viability,
      while the induction of nonapoptotic complement-induced cell death had no effect
      on bacterial viable counts. Infected macrophages also showed a reduced
      susceptibility to FasL-induced apoptosis correlating with a reduced level of Fas
      expression. These data suggest that apoptosis of infected macrophages induced
      through receptors of the TNF family could be an immune effector mechanism not
      only depriving mycobacteria from their growth environment but also reducing
      viable bacterial counts by an unknown mechanism. On the other hand, interference
      by M. tuberculosis with the FasL system might represent an escape mechanism of
      the bacteria attempting to evade the effect of apoptosis.

PMID- 9605149
TI  - T cell- and NK cell-independent inhibition of hepatic metastases by systemic
      administration of an IL-12-expressing recombinant adenovirus.
AB  - IL-12 is a potent immunoregulatory cytokine that has been shown to mediate tumor
      regression in a variety of tumor models. We describe the construction of AdCMV-IL
      12, a recombinant adenovirus that encodes both subunits of IL-12 under
      transcriptional control of the CMV promoter. This recombinant virus efficiently
      infects a wide variety of cell types leading to the production of high levels of
      biologically active IL-12. Because the liver is a primary site of infection after
      i.v.-administered adenovirus, we tested the therapeutic efficacy of this virus in
      a murine hepatic metastasis tumor model. Systemic administration of AdCMV-IL-12
      dramatically inhibited the formation of 3-day Renca hepatic metastases (mean of
      16 metastases per liver) compared with the control virus AdCMV-betagal (mean of
      209) or vehicle alone (mean of 272). Histologic analysis indicated that
      metastatic growth inhibition was accompanied by a dramatic perivascular
      infiltrate consisting of T cells, macrophages, and neutrophils. Therapeutic
      efficacy was not diminished in animals depleted of CD4+ or CD8+ T cells, or in
      SCID mice, even after NK cell ablation. In the latter case, a hepatic
      perivascular infiltrate composed of macrophages and neutrophils was observed
      after AdCMV-IL-12-treatment, while numerous activated Kupffer cells were noted in
      the hepatic parenchyma. Analysis of therapy-induced changes in hepatic gene
      expression demonstrated increased levels of IP-10 and Mig RNAs, but no increase
      in iNOS, Fas, or FasL RNA levels was observed. Our data suggest a model of
      metastatic growth inhibition mediated by nonlymphocyte effector cells including
      macrophages and neutrophils and that may involve anti-angiogenic chemokines.

PMID- 9605148
TI  - Treponema pallidum and Borrelia burgdorferi lipoproteins and synthetic
      lipopeptides activate monocytic cells via a CD14-dependent pathway distinct from
      that used by lipopolysaccharide.
AB  - Lipoproteins of Treponema pallidum and Borrelia burgdorferi possess potent
      proinflammatory properties and, thus, have been implicated as major
      proinflammatory agonists in syphilis and Lyme disease. Here we used purified B.
      burgdorferi outer surface protein A (OspA) and synthetic lipopeptides
      corresponding to the N-termini of OspA and the 47-kDa major lipoprotein immunogen
      of T. pallidum to clarify the contribution of CD14 to monocytic cell activation
      by spirochetal lipoproteins and lipopeptides. As with LPS, mouse anti-human CD14
      Abs blocked the activation of 1,25-dihydroxyvitamin D3-matured human
      myelomonocytic THP-1 cells by OspA and the two lipopeptides. The existence of a
      CD14-dependent pathway was corroborated by using undifferentiated THP-1 cells
      transfected with CD14 and peritoneal macrophages from CD14-deficient BALB/c mice.
      Unlike LPS, cell activation by lipoproteins and lipopeptides was serum
      independent and was not augmented by exogenous LPS-binding protein. Two
      observations constituted evidence that LPS and lipoprotein/lipopeptide signaling
      proceed via distinct transducing elements downstream of CD14: 1) CHO cells
      transfected with CD14 were exquisitely sensitive to LPS but were
      lipoprotein/lipopeptide nonresponsive; and 2) substoichiometric amounts of
      deacylated LPS that block LPS signaling at a site distal to CD14 failed to
      antagonize activation by lipoproteins and lipopeptides. The combined results
      demonstrate that spirochetal lipoproteins and lipopeptides use a CD14-dependent
      pathway that differs in at least two fundamental respects from the well
      characterized LPS recognition pathway.

PMID- 9605150
TI  - IFN-gamma priming up-regulates IFN-stimulated gene factor 3 (ISGF3) components,
      augmenting responsiveness of IFN-resistant melanoma cells to type I IFNs.
AB  - IFN-stimulated gene factor 3 (ISGF3) mediates transcriptional activation of IFN
      sensitive genes (ISGs). The component subunits of ISGF3, STAT1alphabeta, STAT2,
      and p48-ISGF3gamma, are tyrosine phosphorylated before their assembly into a
      complex. Subsequently, the ISGF3 complex is translocated to the nucleus. We have
      recently established that the responsiveness of human melanoma cell lines to type
      I IFNs correlates directly with their intracellular levels of ISGF3 components,
      particularly STAT1. In the present study, we show that pretreating IFN-resistant
      melanoma cell lines with IFN-gamma (IFN-gamma priming) before stimulation with
      type I IFN also results in increased levels of ISGF3 components and enhanced DNA
      binding activation of ISGF3. In addition, IFN-gamma priming of IFN-resistant
      melanoma cell lines increased expression of type I IFN-induced ISG products,
      including ISG54, 2'-5'-oligoadenylate synthase, HLA class I, B7-1, and ICAM-1
      Ags. Furthermore, IFN-gamma priming enhanced the antiviral effect of IFN-beta on
      the IFN-resistant melanoma cell line, MM96. These results support a role for IFN
      gamma priming in up-regulating ISGF3, thereby augmenting the responsiveness of
      IFN-resistant melanoma cell lines to type I IFN and providing a molecular basis
      and justification for using sequential IFN therapy, as proposed by others, to
      enhance the use of IFNs in the treatment of melanoma.

PMID- 9605151
TI  - The role of CD14 in signaling mediated by outer membrane lipoproteins of Borrelia
      burgdorferi.
AB  - Borrelia burgdorferi possesses membrane lipoproteins that exhibit stimulatory
      properties and, consequently, have been implicated in the pathology related to
      Lyme disease. As CD14 has been shown to mediate signaling by a number of lipid
      modified bacterial products, the involvement of CD14 in signaling mediated by two
      B. burgdorferi lipoproteins, outer surface protein A (OspA) and OspC, was
      determined. Lipoprotein-mediated induction of nuclear factor-kappaB nuclear
      translocation and production of IL-8 and IL-6 in HUVEC was enhanced in the
      presence of serum or soluble rCD14. CD14-specific Abs that block LPS-mediated
      signaling also inhibited lipoprotein-dependent signaling in HUVEC and
      neutrophils. The formation of stable complexes between OspA and CD14 was
      demonstrated by native gel electrophoresis. LPS was found to compete with OspA
      for binding with CD14, suggesting that LPS and OspA bind similar regions on CD14.
      The similarity in binding was further supported by the finding that a mutant
      soluble CD14, lacking the LPS binding site, did not facilitate lipoprotein
      signaling, nor did it form a complex with OspA. Binding of OspA to CD14 was
      dependent on the lipid modification, as unlipidated OspA did not form a complex
      with CD14 or stimulate cells. In contrast, the lipopeptide remaining after
      proteinase K digestion both formed a complex with CD14 and retained stimulatory
      properties. These findings indicate that CD14 facilitates bacterial lipoprotein
      signaling in mammalian cells.

PMID- 9605152
TI  - FTY720, a novel immunosuppressant, induces sequestration of circulating mature
      lymphocytes by acceleration of lymphocyte homing in rats. II. FTY720 prolongs
      skin allograft survival by decreasing T cell infiltration into grafts but not
      cytokine production in vivo.
AB  - FTY720, a novel immunosuppressant, prolonged the survival of WKAH skin allografts
      transplanted into MHC-incompatible F344 rats. In this allograft model, the median
      survival time of the control group was 7 days, whereas those of the groups given
      FTY720 orally at 0.1 mg/kg and cyclosporin A (CsA) at 10 mg/kg were 10.5 and 11
      days, respectively. In contrast, FTY720 (0.1 mg/kg) combined with CsA (10 mg/kg)
      synergistically prolonged allograft survival with a median survival time
      exceeding 70 days. To elucidate the mechanisms of this remarkable synergistic
      effect, mRNA expressions of IL-2 and IFN-gamma and that of CD3 (delta-chain),
      which reflects T cell infiltration, in allografts were temporally analyzed using
      a semiquantitative PCR method. In WKAH skin allografts, mRNA levels of IL-2, IFN
      gamma, and CD3 were increased as compared with isograft controls, peaking on days
      4 to 5. CsA (10 mg/kg) significantly inhibited elevations of IL-2 and IFN-gamma
      mRNA, while slightly inhibiting that of CD3 mRNA in allografts. On the contrary,
      FTY720 (0.1 mg/kg) markedly inhibited the elevation of CD3 mRNA, while slightly
      inhibiting those of IL-2 and IFN-gamma mRNA. FTY720 (0.1 mg/kg) combined with CsA
      (10 mg/kg) almost completely suppressed the intragraft expressions of mRNA for IL
      2, IFN-gamma, and CD3. Immunohistochemical staining and flow cytometric analysis
      also confirmed that FTY720 decreased T cell infiltration into allografts. From
      these results, the synergistic effect of FTY720 combined with CsA on prolongation
      of allograft survival is presumably based on the respective inhibitions of T cell
      infiltration and cytokine production in grafts.

PMID- 9605153
TI  - A pathogenic role of IL-12 in blood-stage murine malaria lethal strain Plasmodium
      berghei NK65 infection.
AB  - We studied whether the infection with a blood-stage murine malaria lethal
      Plasmodium berghei NK65 induces IL-12 production, and if so, how the IL-12
      production is involved in the protection or pathogenesis. The infection of
      C57BL/6 mice enhanced mRNA expression of IL-12 p40 and also IFN-gamma, IL-4, and
      IL-10 in both spleen and liver during the early course of the infection. It also
      enhanced the mRNA expression of TNF-alpha, Fas ligand, and cytokine-inducible
      nitric oxide synthase. Increased IL-12 p40 production was also observed in the
      culture supernatant of spleen cells and in sera of infected mice. In addition,
      the infection caused massive liver injury with elevated serum glutamic
      oxaloacetic transaminase and serum glutamic-pyruvic transaminase activities and
      body weight loss. Treatment of these infected mice with neutralizing mAb against
      IL-12 prolonged the survival and diminished the liver injury with reduced
      elevation of serum serum glutamic-oxaloacetic transaminase and serum glutamic
      pyruvic transaminase activities and decreased body weight loss. However, the anti
      IL-12 treatment did not affect parasitemia, and all these mice eventually died.
      Similar results were obtained when infected mice were treated with neutralizing
      mAb against IFN-gamma. Moreover, anti-IL-12 treatment greatly reduced the
      secretion and mRNA expression of IFN-gamma in both spleen and liver. These
      results suggest that the lethal P. berghei NK65 infection induces IL-12
      production and that the IL-12 is involved in the pathogenesis of liver injury via
      IFN-gamma production rather than the protection.

PMID- 9605154
TI  - Control of Leishmania major infection in mice lacking TNF receptors.
AB  - TNF participates in the induction of nitric oxide (NO) production and macrophage
      activation, leading to the elimination of intracellular pathogens. We previously
      found that TNF receptor p55-deficient mice (TNFRp55-/-) control replication of
      Leishmania major in vivo but fail to resolve their lesions. Here we report that
      mice lacking the p75 receptor (TNFRp75-/-) or both receptors (TNFRp55p75-/-),
      also control parasite replication, albeit mice lacking the p55 receptor (either
      TNFRp55-/- or TNFRp55p75-/-) are delayed in their elimination of L. major
      compared with controls. All TNF receptor-deficient mice developed a Thl-type
      immune response and up-regulated inducible NO synthase (iNOS) mRNA gene
      expression in lesions during infection. Thus, neither TNF receptor appears to be
      absolutely required for NO production or elimination of L. major in vivo. In
      vitro, however, while macrophages from naive TNFRp75-/- mice could be activated
      to produce NO and kill L. major, we observed a defect in NO production and
      parasite killing by resident peritoneal macrophages from naive TNFRp55-/- or
      TNFRp55p75-/- mice. However, when macrophages were elicited with leishmanial Ag
      from 4-wk-infected TNFRp55-/- or TNFRp55p75-/- mice, they produced NO and were
      leishmanicidal. These data suggest that the TNFRp75 plays no essential role in L.
      major infection in mice and that the p55 receptor may be required for optimal
      macrophage activation. However, the results also show that a mechanism exists by
      which macrophages can be primed in vivo during L. major infection to produce NO
      and kill L. major in the absence of signaling through either of the TNF
      receptors.

PMID- 9605155
TI  - Nonopsonic and opsonic association of Mycobacterium tuberculosis with resident
      alveolar macrophages is inefficient.
AB  - The association of Mycobacterium tuberculosis with alveolar macrophages (Mphi) in
      a serum-free environment is a crucial first step in the pathogenesis of this
      facultative intracellular pathogen. We present data demonstrating that freshly
      explanted alveolar Mphi do not efficiently bind M. tuberculosis in a serum-free
      system, although a small subpopulation of these Mphi (10-15%) can bind
      mycobacteria. In contrast, almost 100% of a peritoneal Mphi population bind
      mycobacteria under the same conditions. The poor binding of mycobacteria by
      alveolar Mphi does not reflect a general inability to associate with particles;
      binding and ingestion of latex beads and zymosan particles were comparable with
      that seen with peritoneal Mphi. Resident alveolar Mphi did not efficiently bind
      mycobacteria in the presence of serum and expressed poorly several Mphi surface
      receptors, including CR3. Furthermore, we demonstrate that bovine surfactant
      protein A does not enhance the association of M. tuberculosis with alveolar Mphi.
      Differentiation of alveolar Mphi in vitro resulted in increased expression of
      Mphi surface receptors and an increased capacity to bind mycobacteria in the
      presence and absence of serum. Evidence is presented that opsonic binding of M.
      tuberculosis by differentiated alveolar Mphi is mediated by complement and CR3,
      and that the poor binding by resident alveolar Mphi is due to their poor
      expression of CR3. The receptor mediating nonopsonic binding of M. tuberculosis
      to differentiated alveolar Mphi was not unequivocally identified in this study,
      but could also be CR3.

PMID- 9605156
TI  - Differential requirement for CD4 help in the development of an antigen-specific
      CD8+ T cell response depending on the route of immunization.
AB  - Previous studies in our laboratory have shown that DBA/2 mice injected i.p. with
      syngeneic P815 tumor cells transfected with the HLA-CW3 gene (P815-CW3) showed a
      dramatic expansion of activated CD8+CD62L- T cells expressing exclusively the
      Vbeta10 segment. We have used this model to study the regulatory mechanisms
      involved in the development of the CW3-specific CD8+ response, with respect to
      different routes of immunization. Whereas both intradermal (i.d.) and i.p.
      immunization of DBA/2 mice with P815-CW3 cells led to a strong expansion of
      CD8+CD62L-Vbeta10+ cells, only the i.d. route allowed this expansion after
      immunization with P815 cells transfected with a minigene coding for the antigenic
      epitope CW3 170-179 (P815 miniCW3). Furthermore, depletion of CD4+ T cells in
      vivo completely abolished the specific response of CD8+CD62L-Vbeta10+ cells and
      prevented the rejection of P815-CW3 tumor cells injected i.p., whereas it did not
      affect CD8S+CD62L-Vbeta10+ cell expansion after i.d. immunization with either
      P815-CW3 or P815 miniCW3. Finally, the CW3-specific CD8+ memory response was
      identical whether or not CD4+ T cells were depleted during the primary response.
      Collectively, these results suggest that the CD8+ T cell response to P815-CW3
      tumor cells injected i.p. is strictly dependent upon recognition of a helper
      epitope by CD4+ T cells, whereas no such requirement is observed for i.d.
      injection.

PMID- 9605157
TI  - Heparin-binding protein (CAP37) is internalized in monocytes and increases LPS
      induced monocyte activation.
AB  - Previous studies have shown that the neutrophil-derived heparin-binding protein
      (HBP), also known as CAP37 or azurocidin, potentiates the LPS-induced release of
      proinflammatory cytokines (TNF-alpha, IL-1, and IL-6) from isolated human
      monocytes. To date, the mechanisms by which HBP enhances LPS-induced monocyte
      activation have not been elucidated, and it is not known whether HBP also
      increases the LPS-induced production of other bioactive substances. We studied
      human monocytes activated by recombinant human HBP and LPS and their interaction
      with the LPS receptor CD14. We hypothesized that the stimulatory effect of HBP on
      the LPS-induced release of proinflammatory mediators from monocytes was mediated
      by specific binding of HBP to monocytes, which resulted in an up-regulation of
      CD14. Our results demonstrated that HBP alone (10 microg/ml) stimulated the
      production of TNF-alpha from isolated monocytes. In addition, HBP had an additive
      effect on LPS-induced production of TNF-alpha and PGE2, suggesting a generalized
      monocyte activation. We used flow cytometry to demonstrate that HBP had a high
      affinity to monocytes but not to the LPS receptor CD14, and experiments performed
      at 4 degrees C indicated an energy-dependent step in this process. Confocal
      microscopy showed that monocytes internalize HBP within 30 min. These data
      suggest that mechanisms other than increased CD14 expression are responsible for
      the enhanced release of TNF-alpha or PGE2 in response to HBP and LPS.

PMID- 9605158
TI  - Reversible expression of tryptases and chymases in the jejunal mast cells of mice
      infected with Trichinella spiralis.
AB  - It is has been established that mouse mast cells (MCs) can reversibly alter their
      expression of serglycin proteoglycans and the homologous granule chymases that
      have been designated mouse MC protease (mMCP)-1, mMCP-2, and mMCP-5 in vivo.
      Nevertheless, it remained to be determined whether these immune cells could
      modify their expression of other chymases and the granule tryptases mMCP-6 and
      mMCP-7. As assessed immunohistochemically, we now show that MCs reversibly change
      their expression of the recently described chymase mMCP-9 and both tryptases as
      these cells traverse the jejunum during the amplification and regression stages
      of the reactive MC hyperplasia. In noninfected mice, most jejunal MCs reside in
      the submucosa and express mMCP-6 and mMCP-7, but not mMCP-9 or the chymase mMCP
      2. During the inductive phase of the helminth-induced inflammation, when the
      jejunal MCs move from the submucosa to the tips of the villus, the MCs briefly
      express mMCP-9, cease expressing mMCP-6 and mMCP-7, and then express mMCP-2.
      During the recovery phase of the inflammation, jejunal MCs cease expressing mMCP
      2 and then express varied combinations of mMCP-6, mMCP-7, and mMCP-9 as they move
      from the tips of the villus back toward the submucosa. In other model systems,
      mMCP-6 elicits neutrophil extravasation, and mMCP-7 regulates fibrin deposition
      and fibrinogen-mediated signaling events. Thus, the ability of a jejunal MC to
      reversibly alter its tryptase expression during an inflammatory event has
      important functional implications.

PMID- 9605159
TI  - Sulfonylureas inhibit cytokine-induced eosinophil survival and activation.
AB  - Eosinophils play a key role in the pathogenesis of asthma and other allergic
      inflammatory diseases. We have previously shown that treatment of eosinophils
      with lidocaine preferentially inhibits IL-5-induced survival. This inhibition
      cannot be overcome by increasing concentrations of IL-5 and is not due to the
      blocking of Na+ channels by lidocaine. Here we report that one class of K+
      channel blockers, the sulfonylureas, inhibits eosinophil survival in a manner
      similar to lidocaine. The sulfonylurea glyburide inhibits eosinophil survival
      even at high concentrations of IL-5. In contrast, increasing concentrations of IL
      3 or granulocyte-macrophage CSF overcome glyburide inhibition. Glyburide also
      blocks cytokine-induced eosinophil superoxide production. Similar results were
      seen with the sulfonylureas tolbutamide and glipizide. Interestingly, the effects
      of glyburide are not antagonized by the ATP-sensitive K+ channel openers
      cromakalim, pinacidil, or diazoxide. Although Scatchard analysis of [3H]glyburide
      binding to eosinophil membranes indicated that the high affinity sulfonylurea
      receptor (SUR1) is not present on eosinophils, human eosinophils do express mRNA
      homologous to the sulfonylurea receptor family, in keeping with the presence of a
      sulfonylurea receptor. Finally, coculture of eosinophils with combinations of
      glyburide, lidocaine, and dexamethasone resulted in synergistic inhibition of
      cytokine-mediated eosinophil survival and superoxide production. These results
      have intriguing clinical implications for the treatment of eosinophil-associated
      diseases.

PMID- 9605160
TI  - Mast cells enhance eosinophil survival in vitro: role of TNF-alpha and
      granulocyte-macrophage colony-stimulating factor.
AB  - Mast cell-eosinophil interactions in allergy have not yet been completely
      defined. To determine whether mast cells influence eosinophil survival, human
      peripheral blood eosinophils were incubated with rat peritoneal mast cell
      sonicate. After 3 days, viable eosinophils in medium were 21.3% compared with 44%
      with mast cell sonicate. Like sonicate, supernatants of compound 48/80-activated
      mast cells enhanced eosinophil survival, demonstrating that the factor(s)
      involved is stored preformed and rapidly released. Increased eosinophil survival
      was due to an inhibition of apoptosis (morphologic analysis; annexin V/PI).
      Neutralizing Abs to granulocyte-macrophage CSF (GM-CSF), but not to IL-3 or IL-5,
      decreased by 61.7% the enhancing effect on eosinophil viability. Eosinophils are
      the source of GM-CSF since its release in the culture medium was inhibited by
      their incubation with the mast cell sonicate together with dexamethasone. In
      addition, eosinophils incubated with the sonicate expressed mRNA for GM-CSF. To
      partially characterize the mast cell-derived factor(s) increasing eosinophil
      survival, the sonicate was heated (56 degrees C/30 min or 100 degrees C/10 min)
      or preincubated with antihistamines or with anti-TNF-alpha-neutralizing Abs. Most
      of the activity was heat labile. TNF-alpha was found to be predominantly (70%)
      responsible, while histamine had no role. Mast cell sonicate also caused
      eosinophils to release eosinophil peroxidase and to display morphologic signs of
      activation. In conclusion, we have demonstrated that mast cells enhance
      eosinophil survival in part through their activation to produce and release the
      autocrine survival cytokine GM-CSF.

PMID- 9605161
TI  - Cloning and characterization of mouse vascular adhesion protein-1 reveals a novel
      molecule with enzymatic activity.
AB  - Human vascular adhesion protein-1 (VAP-1) is a sialylated endothelial cell
      adhesion molecule mediating the initial L-selectin-independent interactions
      between lymphocytes and endothelial cells in man. In this work we cloned and
      characterized mouse VAP-1 (mVAP-1) and produced an anti-mVAP-1 mAb against a
      recombinant mVAP-1 fusion protein. The isolated cDNA encodes a novel 84.5-kDa
      mouse molecule. The anti-mVAP-1 mAb stained high endothelial venules in
      peripheral lymph nodes, and smooth muscle cells and lamina propria vessels in
      gut. During immunoblotting, this anti-mVAP-1 mAb recognized a 110/220-kDa Ag,
      suggesting that mVAP-1 is a dimer. Since mVAP-1 has significant sequence identity
      to members of a family of enzymes called the copper-containing amine oxidases, we
      showed that mVAP-1 possesses monoamine oxidase activity. Thus, mVAP-1 is the
      first mouse membrane-bound amine oxidase identified at the molecular level. Based
      on the 83% identity between the isolated cDNA and human VAP-1 cDNA, the
      expression pattern, the molecular mass, and the enzyme activity against
      monoamines, the cloned molecule represents a mouse homologue of human VAP-1.
      Cloning of mVAP-1 provides a valuable tool for in vivo studies of the
      significance of VAP-1 for lymphocyte-endothelial cell interactions and of the
      possible relationship between leukocyte adhesion and amine oxidase activity.

PMID- 9605162
TI  - Human beta 2-glycoprotein I binds to endothelial cells through a cluster of
      lysine residues that are critical for anionic phospholipid binding and offers
      epitopes for anti-beta 2-glycoprotein I antibodies.
AB  - Beta 2-Glycoprotein I (beta 2GPI) is a phospholipid-binding protein recognized by
      serum autoantibodies from the anti-phospholipid syndrome both in cardiolipin- and
      beta 2GPI-coated plates. We found that: 1) recombinant wild-type beta 2GPI bound
      to HUVEC and was recognized by both human monoclonal IgM and affinity-purified
      polyclonal IgG anti-beta 2GPI anti-phospholipid syndrome Abs; and 2) a single
      amino acid change from Lys286 to Glu significantly reduced endothelial adhesion.
      Double and triple mutants (from Lys284,287 to Glu284,287, from Lys286,287 to
      Glu286,287, and from Lys284,286,287 to Glu284,286,287) completely abolished
      endothelial binding. A synthetic peptide (P1) spanning the sequence Glu274-Cys288
      of the beta 2GPI fifth domain still displayed endothelial adhesion. Another
      peptide (P8), identical with P1 except that Cys281 and Cys288 were substituted
      with serine residues, did not bind to HUVEC. Anti-beta 2GPI Abs, once bound to P1
      adhered to HUVEC, induced E-selectin expression and up-regulated IL-6 secretion.
      Control experiments conducted with irrelevant Abs as well as with the P8 peptide
      did not show any endothelial Ab binding nor E-selectin and IL-6 modulation. Our
      results suggest that: 1) beta 2GPI binds to endothelial cells through its fifth
      domain; 2) the major phospholipid-binding site that mediates the binding to
      anionic phospholipids is also involved in endothelial binding; 3) HUVEC provide a
      suitable surface for beta 2GPI binding comparable to that displayed by anionic
      phospholipids dried on microtiter wells; and 4) the formation of the complex
      between beta 2GPI and the specific Abs leads to endothelial activation in vitro.

PMID- 9605163
TI  - Coengagement of ICAM-3 and Fc receptors induces chemokine secretion and spreading
      by myeloid leukocytes.
AB  - ICAM-3 is expressed at high levels on myeloid leukocytes, but its function on
      these cells is unknown. We tested the hypothesis that it transduces outside-in
      proinflammatory signals using immobilized mAbs to engage ICAM-3 on freshly
      isolated human monocytes and neutrophils. Two immobilized Abs that recognize
      epitopes in the extracellular domain 1 of ICAM-3, which is critical for
      recognition by the alphaL/beta2 integrin, potently induced secretion of MIP
      1alpha, IL-8, and MCP-1 by monocytes and triggered IL-8 secretion by neutrophils.
      These chemokines are products of immediate-early genes that are induced when
      myeloid cells are activated. Chemokine secretion induced by "triggering" Abs was
      greater than that induced by isotype-matched immobilized Abs against ICAM-1, ICAM
      2, PECAM-1, control Igs, or immobilized control proteins. Coengagement of ICAM-3
      and Fc receptors (FcgammaRI or FcgammaRII) was required for maximal chemokine
      secretion by monocytes. Microscopy documented that there is also dramatic
      spreading of monocytes when surface ICAM-3 is engaged by immobilized Abs.
      Spreading was induced by Fab and F(ab')2 fragments of triggering anti-ICAM-3 mAb,
      demonstrating direct outside-in signaling, but was not required for chemokine
      secretion. These experiments indicate that ICAM-3 may transmit outside-in signals
      when it is engaged by beta2 integrins during myeloid cell-cell interactions in
      inflammatory lesions. Binding of Fc receptors by Ig in the local environment can
      amplify the responses.

PMID- 9605164
TI  - Prevention and treatment of experimental autoimmune encephalomyelitis by CNI
      1493, a macrophage-deactivating agent.
AB  - Multiple sclerosis (MS) and its animal model, experimental autoimmune
      encephalomyelitis (EAE), are characterized by episodic neurologic dysfunction,
      perivascular mononuclear cell inflammation occurring mainly in white matter, and
      demyelination. Strong circumstantial evidence supports the conclusion that
      macrophage activation and local production of proinflammatory cytokines are
      necessary for disease induction and lesion formation. We now report that CNI
      1493, a small m.w. compound, which inhibits macrophage activation and subsequent
      proinflammatory cytokine production, suppresses EAE induced in the genetically
      susceptible SJL/J mouse. Treatment with 5 mg/kg/day completely suppressed mild
      disease (clinical index of 1.6 +/- 0.5 in the untreated group as compared with
      0.0 +/- 0.0 for the treated group) and significantly reduced acute disease
      (clinical index of 4.3 +/- 0.7 in the untreated group as compared with 0.5 +/-
      0.3 for the treated group). Suppression of clinical manifestations of the disease
      correlated with a significant decrease in histopathology and proinflammatory
      cytokine expression at the lesion site. Moreover, drug treatment during the
      chronic phase resulted in amelioration of clinical signs. The data presented here
      should prove useful in developing novel chemotherapeutic approaches for the
      treatment of MS.

PMID- 9605166
TI  - Potassium leakage during the apoptotic degradation phase.
AB  - The subcellular compartmentalization of ions is perturbed during the process of
      apoptosis. In this work, we investigated the impact of K+ on the apoptotic
      process in thymocytes and T cell hybridoma cells. Irrespective of the death
      inducing stimulus (glucocorticoids, topoisomerase inhibition, or Fas
      crosslinking), a significant K+ outflow was observed during apoptosis, as
      determined on the single-cell level by means of the K+-sensitive fluorochrome,
      benzofuran isophtalate. This loss of cytosolic K+ only occurs in cells that have
      completely disrupted their inner mitochondrial transmembrane potential.
      Inhibition of this mitochondrial transmembrane potential loss by Bcl-2 or by
      specific inhibitors acting on the mitochondrial permeability transition pore
      (bongkrekic acid, cyclosporin A) prevents K+ leakage. K+ drops at the same stage
      at which cells expose phosphatidylserine residues on the outer leaflet of the
      membrane and reduce the levels of nonoxidized glutathione, but before they
      hyperproduce reactive oxygen species, undergo massive Ca2+ influx, shrink, and
      lyse. In a cell-free system of apoptosis, isolated nuclei exposed to the
      supernatant of mitochondria that have undergone permeability transition only
      manifest chromatinolysis when the K+ concentration is lowered from physiologic to
      apoptotic levels. Accordingly, massive DNA fragmentation causing subdiploidy is
      confined to cells that have undergone K+ leakage. Together, these data point to
      the step-wise acquisition of membrane dysfunction in apoptosis and indicate an
      important role for the disruption of normal K+ homeostasis in apoptotic
      degradation. Derepression of endonucleases due to low K+ concentrations may be a
      decisive prerequisite for end-stage DNA fragmentation.

PMID- 9605165
TI  - Interaction of vaccinia virus complement control protein with human complement
      proteins: factor I-mediated degradation of C3b to iC3b1 inactivates the
      alternative complement pathway.
AB  - Vaccinia virus complement control protein (VCP) is a virulence determinant of
      vaccinia virus that helps protect the virus from the complement attack of the
      host. To characterize the interaction of VCP with C3 and C4 and understand the
      mechanism by which VCP inactivates complement, we have expressed VCP in a yeast
      expression system and compared the biologic activity of the purified protein to
      that of human factor H and complement receptor 1 (CR1). Recombinant VCP bound to
      C3 and the proteolytically cleaved form of C3 (C3b), but not to the 135,300-m.w.
      fragment of C3 generated using elastase (C3c) and the 35,000-m.w. fragment of C3
      generated using elastase (C3d) and inhibited both the classical and alternative
      pathways of complement activation. Although rVCP was less effective at inhibiting
      the alternative pathway than factor H or CR1, it was more effective than factor H
      at inhibiting the classical pathway. Unlike factor H, rVCP was unable
      discriminate between alternative pathway-mediated lysis of rabbit and sheep E. A
      comparison of the cofactor activity in factor I-mediated cleavage of C3b
      suggested that in contrast to factor H and CR1, which displayed cofactor activity
      for the three sites, rVCP displayed cofactor activity primarily for the first
      site, leading to generation of C3b cleaved by factor I between Arg1281-Ser1282
      (iC3b1). Its cofactor activity for C4b cleavages was similar to that of soluble
      complement receptor type 1. Purification and functional analysis of iC3b1 showed
      that it was unable to interact with factor B to form the alternative pathway C3
      convertase, C3b,Bb. These results suggest that the interaction of VCP with C3 is
      different from that of factor H and CR1 and that VCP-supported first cleavage of
      C3b by factor I is sufficient to render C3b nonfunctional.

PMID- 9605167
TI  - Novel C5a receptor antagonists regulate neutrophil functions in vitro and in
      vivo.
AB  - Novel recombinant human C5a receptor antagonists were discovered through
      modification of the C terminus of C5a. The C5a1-71T1M,C27S,Q71C monomer, (C5aRAM;
      CGS 27913), was a pure and potent functional antagonist. The importance of a C
      terminal cysteine at position 71 to antagonist properties of C5aRAM was confirmed
      by studying C5a1-71 derivatives with replacements of Q71, C5a derivatives of
      various lengths (70-74) with C-terminal cysteines, and C5a derivatives of various
      lengths (71-74) with Q71C replacements. The majority of C5a1-71Q71 derivatives
      were agonists (C5a-like) in the human neutrophil C5a-induced intracellular
      calcium mobilization assay. The C5a1-71Q71C derivative was an antagonist. C5a
      derivatives of lengths 73 and 74 with C-terminal cysteines were agonists, while
      lengths 70 to 72 were antagonists. C5a derivatives of lengths 72, 73, and 74 with
      Q71C replacements were agonists, while, again, C5a1-71Q71C was an antagonist.
      C5aRAM and its adducts, including its dimer, C5aRAD (CGS 32359), were pure
      antagonists. Additionally, CSaRAM and CSaRAD inhibited binding of 125I-labeled
      recombinant human C5a to neutrophil membranes (Ki = 79 and 2 pM, respectively),
      C5a-stimulated neutrophil intracellular calcium mobilization (8 and 13 nM), CD11b
      integrin up-regulation (10 and 1 nM), superoxide generation (182 and 282 nM),
      lysozyme release (1 and 2 microM), and chemotaxis (11 and 7 microM). In vivo,
      intradermal injection of C5aRAM inhibited C5a-induced dermal edema in rabbits.
      Furthermore, a 5-mg/kg i.v. bolus of C5aRAD significantly inhibited C5a-induced
      neutropenia in micropigs when challenged with C5a 30 min after C5aRAD
      administration. C5aRAM and C5aRAD are novel, potent C5a receptor antagonists
      devoid of agonist or proinflammatory activity with demonstrated efficacy in vitro
      and in vivo.

PMID- 9605168
TI  - Differential regulation of chemoattractant-stimulated beta 2, beta 3, and beta 7
      integrin activity.
AB  - Leukocyte adhesion to endothelium and extravasation are dynamic processes that
      require activation of integrins. Chemoattractants such as IL-8 and FMLP are
      potent activators of leukocyte integrins. To compare the chemoattractant
      stimulated activation of three integrins, alpha 4 beta 7, alpha L beta 2, and
      alpha V beta 3, in the same cellular context, we expressed an IL-8 receptor (IL
      8RA) and FMLP receptor (FPR) in the lymphoid cell line JY. Chemoattractants
      induced a rapid increase in alpha L beta 2- and alpha V beta 3-dependent JY
      adhesion within 5 min, and it was sustained for 30 min. In contrast, stimulation
      of alpha 4 beta 7-dependent adhesion was transient, returning to basal levels by
      30 min. The activation profiles of the integrins were similar regardless of
      whether IL-8 or FMLP was used for induction. We also demonstrate that alpha 4
      beta 7-dependent adhesion was uniquely responsive to the F actin-disrupting agent
      cytochalasin D and the protein kinase C (PKC) inhibitor chelerythrin. While alpha
      V beta 3- and alpha L beta 2-mediated cell adhesion was significantly reduced by
      cytochalasin D, alpha 4 beta 7-mediated adhesion was enhanced. Chelerythrin
      inhibited both the IL-8 and PMA activation of alpha L beta 2 and alpha V beta 3.
      In contrast, inducible alpha 4 beta 7 activity was unaffected, and basal activity
      was increased. These findings demonstrate that the mechanism of alpha 4 beta 7
      regulation by chemoattractants is different from that of alpha L beta 2 and alpha
      V beta 3 and that it appears to involve distinct cytoskeletal and PKC
      dependencies. In addition, PKC activity may be a positive or negative regulator
      of integrin-dependent adhesion.

PMID- 9605169
TI  - The role of two distinct endothelial molecules, vascular adhesion protein-1 and
      peripheral lymph node addressin, in the binding of lymphocyte subsets to human
      lymph nodes.
AB  - Lymphocyte binding to high endothelial venules (HEV) in noninflamed peripheral
      lymph nodes (PLN) relies heavily on two endothelial adhesion molecules called
      vascular adhesion protein-1 (VAP-1) defined by mAb 1B2 and the peripheral lymph
      node addressins (PNAd) defined by mAb MECA-79. Data from several different groups
      indicate that these two molecules share several characteristics in expression,
      biochemical structure, and function, raising the possibility that VAP-1 may be
      identical to the 170- and 90-kDa species of PNAd glycoproteins. In this study, we
      show that many PLN HEV coexpress these two molecules. In parallel SDS-PAGE
      analyses, the m.w. of the 90- and 170-kDa forms of these molecules are
      indistinguishable. Nevertheless, we show by different metabolic labelings, by
      reciprocal cross-precipitations, and by immunofluorescence stainings of newly
      established VAP-1 transfectants that the 90- and 170-kDa species of PNAd and VAP
      1 are distinct molecules. In functional terms, VAP-1 is strikingly selective in
      mediating PLN HEV adhesion of CD8-positive, but not of CD4-positive T cells. In
      contrast, PNAd contributes to the adhesion of both CD4-positive and CD8-positive
      cells to these vessels. Together, these data show that initial adhesion of CD8
      positive lymphocytes to PLN HEV requires a PNAd- and a VAP-1-dependent step that
      are both essential and may occur simultaneously or sequentially.

PMID- 9605170
TI  - IL-4-induced eosinophil accumulation in rat skin is dependent on endogenous TNF
      alpha and alpha 4 integrin/VCAM-1 adhesion pathways.
AB  - IL-4 has been implicated in the pathogenesis of a number of allergic inflammatory
      disease states where the accumulation of eosinophils is a prominent feature. The
      aim of the present study was to use an isotopic in vivo model to investigate the
      ability of recombinant rat IL-4 in inducing eosinophil accumulation in rat skin.
      111In-eosinophil accumulation in response to intradermally injected IL-4 was
      measured during 0 to 4 h, 24 to 28 h, and 48 to 52 h. Accumulation was detected
      during the first two periods, but not at the later time point. The accumulation
      during 24 to 28 h, which was dose dependent, was investigated in detail.
      Administration i.v. of an anti-rat VCAM-1 mAb, but not an anti-rat ICAM-1 mAb,
      inhibited the accumulation of 111In-eosinophils induced by IL-4 (maximum
      inhibition, 80%). Further, when the 111In-eosinophils were pretreated in vitro
      with an anti-beta 2 integrin mAb, an anti-alpha 4 integrin mAb, or a combination
      of both mAbs, before their injection into recipient rats, the IL-4-induced cell
      accumulation was inhibited by 63, 60, and 74%, respectively. Finally,
      coadministration of IL-4 with the soluble TNF receptor (p55)-IgG fusion protein
      significantly reduced the 111In-eosinophil accumulation induced by the cytokine,
      and TNF-alpha was detected in IL-4-injected skin sites by both immunostaining and
      bioassay. Our results demonstrate that IL-4 is a potent inducer of eosinophil
      accumulation in vivo, the response being dependent on the endogenous generation
      of TNF-alpha, beta 2 integrins, and alpha 4 integrin/VCAM-1 interactions.

PMID- 9605171
TI  - Receptors for the anaphylatoxin C5a (CD88) on human mesangial cells.
AB  - In these studies, we determined whether there are receptors for the anaphylatoxin
      C5a (C5aR, CD88) on human mesangial cells (HMC). To prepare Abs to C5aR, we first
      synthesized an immunogenic peptide spanning residues 8-32 of the molecule, and
      this peptide was used to immunize rabbits. Anti-C5aR antiserum, but not preimmune
      serum, stained fixed and unfixed HMC in culture. By Western blotting anti-C5aR,
      Abs identified a 49.6-kDa protein in HMC. By reverse-transcription PCR, a cDNA
      product of 558 bp was amplified corresponding to the expected size of C5aR cDNA.
      A cDNA of the same size was amplified simultaneously from human PBL. Restriction
      mapping of the products amplified from HMC and from PBL gave restriction
      fragments of the same size. Incubation of HMC with increasing doses of C5a caused
      a progressive increase in the levels of the transcription factors activator
      protein-1 (AP-1) and cAMP response element binding protein (CREB), but C5a had no
      effect on the level of nuclear factor-kappaB (NF-kappaB). The effects of C5a on
      AP-1 were concentration and time dependent and peaked after 60 min. In contrast,
      the C5a metabolite C5adesArg had no significant effect on AP-1 levels.
      Preincubation of HMC with rabbit anti-C5aR antiserum inhibited partially the
      effect of C5a on AP-1. However, anti-C5aR Abs alone had no appreciable effects on
      AP-1. C5a caused a significant up-regulation of mRNA for the early response genes
      c-jun and c-fos on HMC. These results provide evidence for the presence of C5aR
      in adult HMC in culture and indicate that, after binding to C5aR, the
      anaphylatoxin C5a causes significant up-regulation of certain transcription
      factors and early response genes.

PMID- 9605172
TI  - Soluble IL-15 receptor alpha-chain administration prevents murine collagen
      induced arthritis: a role for IL-15 in development of antigen-induced
      immunopathology.
AB  - IL-15 has recently been detected in the synovium of patients with rheumatoid
      arthritis. IL-15-activated T cells induce significant TNF-alpha synthesis by
      macrophages via a cell contact-dependent mechanism, suggesting a key regulatory
      role for IL-15. Here, we report that the administration of a soluble fragment of
      IL-15Ralpha into DBA/1 mice, profoundly suppressed the development of collagen
      induced arthritis. This was accompanied in vitro by marked reductions in Ag
      specific proliferation and IFN-gamma synthesis by spleen cells from treated mice
      compared with control mice and in vivo by a significant reduction in serum anti
      collagen Ab levels. These data directly demonstrate a pivotal role for IL-15 in
      the development of inflammatory arthritis and also suggest that antagonists to IL
      15 may have therapeutic potential in rheumatic diseases.

PMID- 9605174
TI  - The Fas counterattack in vivo: apoptotic depletion of tumor-infiltrating
      lymphocytes associated with Fas ligand expression by human esophageal carcinoma.
AB  - Various cancer cell lines express Fas ligand (FasL) and can kill lymphoid cells
      by Fas-mediated apoptosis in vitro. FasL expression has been demonstrated in
      several human malignancies in vivo. We sought to determine whether human
      esophageal carcinomas express FasL, and whether FasL expression is associated
      with increased apoptosis of tumor-infiltrating lymphocytes (TIL) in vivo, thereby
      contributing to the immune privilege of the tumor. Using in situ hybridization
      and immunohistochemistry, respectively, FasL mRNA and protein were colocalized to
      neoplastic esophageal epithelial cells in all esophageal carcinomas (squamous, n
      = 6; adenocarcinoma, n = 2). The Extent of FasL expression was variable, with
      both FasL-positive and FasL-negative neoplastic regions occurring within tumors.
      TIL were detected by immunohistochemical staining for the leukocyte common Ag,
      CD45. FasL expression was associated with a mean fourfold depletion of TIL when
      compared with FasL-negative areas within the same tumors (range 1.6- to 12-fold,
      n = 6,p < 0.05). Cell death of TIL was detected by dual staining of CD45
      (immunohistochemistry) and DNA strand breaks (TUNEL, terminal deoxynucleotidyl
      transferase-mediated dUTP nick end labeling). There was a mean twofold increase
      in detectable cell death among TIL in FasL-positive areas compared with FasL
      negative areas (range 1.6- to 2.4-fold, n = 6, p < 0.05). In conclusion, we
      demonstrate a statistically significant, quantitative reduction of TIL
      concomitant with significantly increased TIL apoptosis within FasL-expressing
      areas of esophageal tumors. Our findings suggest Fas-mediated apoptotic depletion
      of TIL in response to FasL expression by esophageal cancers, and provide the
      first direct, quantitative evidence to support the Fas counterattack as a
      mechanism of immune privilege in vivo in human cancer.

PMID- 9605176
TI  - Design and validation of a new image analysis method for automatic quantification
      of interstitial fibrosis and glomerular morphometry.
AB  - Interstitial fibrosis and morphologic changes in kidney glomeruli, the structural
      effects of many diseases, lead to significant pathologic alterations. A reliable
      and objective method to accurately quantify the extent of interstitial fibrosis
      and the degree of alteration in glomerular morphology is needed for both clinical
      practice and experimental work. The morphometric methods of quantification
      described to date are time-consuming and require trained personnel. This article
      describes the design and validation of an image analysis-based application
      (Fibrosis HR) for automatically and rapidly quantifying interstitial fibrosis and
      glomerular morphology in the same tissue section stained with Sirius red. The
      image processing algorithms described herein automatically segment interstitial
      fibrosis and mesangial matrix using automatic thresholding and morphologic
      filtering. The glomerular region is extracted by a simple interactive step and an
      automatic mathematical morphology algorithm, whereas the glomerular tuft is
      automatically segmented with automatic thresholding and a sequence of Boolean and
      mathematical morphology operations. All extracted areas are automatically
      quantified in absolute (microm2) and relative (%) values. For validation of this
      method, interstitial fibrosis, mesangial matrix, and glomerular and glomerular
      tuft areas were manually segmented and their quantifications statistically
      compared with those obtained automatically. Statistical analyses showed
      significant intra- and interoperator variability in manual segmentation of
      interstitial fibrosis, mesangial matrix, and glomerular tuft areas. Automatic
      quantifications of the same areas did not differ significantly from their mean
      manual evaluations. There was no significant intra- or interoperator variability
      in the interactive identification of the glomerular region. In conclusion,
      Fibrosis HR produces robust, fully reproducible, accurate, objective, and
      reliable quantifications, which facilitate the evaluation of in vivo experimental
      models of renal interstitial and glomerular pathologies and improve the accuracy
      of clinicopathologic analyses of renal diseases in human biopsies.

PMID- 9605175
TI  - The effect of deletion of the V3 loop of gp120 on cytotoxic T cell responses and
      HIV gp120-mediated pathogenesis.
AB  - New strategies for improving the efficacy of HIV vaccines are of significant
      importance. In this study, we analyzed the effect of deletion of the
      hypervariable V3 loop of gp120 on envelope (env)-specific CTL responses in PBMC
      of HIV-infected individuals. We showed increased CTL activities against conserved
      epitopes of the env glycoprotein in cultures induced with the AV3 mutant compared
      with those stimulated with the full-length env gene products. In contrast to the
      wild-type env, the AV3 mutant-expressing cells were resistant to Ab-dependent
      cell-mediated cytotoxicity, formed no syncytia, and neither underwent nor induced
      apoptosis in CD4+ cells. Thus, the AV3 mutant may redirect immune responses
      toward conserved epitopes of gp160, has longer expression time due to increased
      resistance to Ab-dependent cell-mediated cytotoxicity, and does not trigger
      cytopathic effects associated with apoptosis and syncytium formation. This
      approach may apply to other Ags of HIV, where deletions of highly variable or
      immunosuppressive epitopes may improve the efficacy of HIV vaccines.

PMID- 9605173
TI  - Theiler's virus infection of genetically susceptible mice induces central nervous
      system-infiltrating CTLs with no apparent viral or major myelin antigenic
      specificity.
AB  - Intracranial infection of susceptible mice with Theiler's virus results in
      persistent infection and spinal cord demyelination similar to human multiple
      sclerosis. While central nervous system infiltrating lymphocytes (CNS-ILs) in
      these mice display no virus-specific CTL activity, the cells were found to be
      activated killers using a specificity-independent assay. We previously
      demonstrated that the depletion of T cells in persistently infected mice
      significantly decreases demyelinating disease. Consequently, we have investigated
      the killing pathways employed by CNS-ILs that are isolated from persistently
      infected animals, the relative contribution of CD4 and CD8 cells in the
      generation of these CTLs, and the reactivity of this cell population to two
      putative autoantigens in the CNS. In vitro or in vivo manipulation of T cell
      populations using Abs or genetic knockout strategies demonstrate that the
      cytotoxic activity is primarily mediated by CD8+ T cells, and that perforin is an
      important molecule in the effector pathway. Since effector functions in infected
      mice were not inhibited by the depletion of CD4 cells with mAb but was blocked
      genetically in CD4 knockout mice, CD4+ T cells appear to play a helper role in
      the generation of CD8+ CTLs. We found no evidence of autoimmune-mediated
      demyelination, as the CD8+ CTLs were not reactive to two major myelin
      autoantigens, myelin basic protein and proteolipid protein. Our finding that CNS
      ILs that are isolated from mice susceptible to persistent virus infection are
      neither specific for virus or myelin autoantigens is consistent with the
      possibility that CD8+ CTLs mediate CNS damage as a result of nonspecific
      activation by virus.

PMID- 9605178
TI  - Serum amyloid A protein induces production of matrix metalloproteinases by human
      synovial fibroblasts.
AB  - Serum amyloid A (SAA) is a precursor protein for amyloid A, which is a
      constituent for amyloid fibrils in secondary amyloidosis. To determine the role
      of SAA in the articular destruction in patients with rheumatoid arthritis (RA),
      we investigated the effects of SAA on the production of matrix metalloproteinases
      (MMPs) by rheumatoid synovial fibroblasts. SAA stimulated rheumatoid synovial
      fibroblasts to produce MMP-2 and MMP-3 in a dose-dependent manner. Pretreatment
      of synovial fibroblasts with cycloheximide prevented SAA-mediated MMP-2 and MMP-3
      secretion. When SAA-containing media were immunodepleted by anti-SAA-specific
      antibody, SAA-mediated MMP secretion was also abrogated. The level of MMP-3 mRNA
      was increased in SAA-stimulated synovial fibroblasts compared with that of
      control cells. Our data indicate that SAA is a potent inducer of MMPs in the RA
      synovium and may play a critical role in the degradation of extracellular matrix
      in the rheumatoid joint.

PMID- 9605177
TI  - Anti-inflammatory and antisecretory potential of histidine in Salmonella
      challenged mouse small intestine.
AB  - Challenge of mouse small intestinal loops with Salmonella typhimurium invoked the
      accumulation of luminal fluid, acute inflammation, and extensive structural
      damage to the small intestinal mucosa, as determined by histology and electron
      microscopy. Intraperitoneal and intestinal luminal injection of L-histidine, a
      known antioxidant, reduced the amount of fluid accumulating in the intestinal
      lumen and protected the intestinal tissue from S. typhimurium-induced damage. The
      reduction in S. typhimurium-induced fluid accumulation by L-histidine was
      specific for the L-enantiomer because D-histidine had no significant protective
      effect. Efficacy of L-histidine in protecting the infected intestinal tissue was
      attributed to the capacity of the imidazole ring to scavenge reactive oxygen
      species (ROS) generated by cells in the intestine during the acute inflammatory
      response. Glutathione levels were markedly reduced in S. typhimurium-challenged,
      inflamed intestinal tissues as a result of ROS generation. Importantly, after
      dosing the S. typhimurium-challenged mice with L-histidine, the glutathione
      content of the small intestinal tissue was not significantly different from mock
      challenged controls. Further evidence favoring this mechanism included the
      capacity of L-histidine to scavenge ROS produced as a result of
      lipopolysaccharide (LPS) exposure of mononuclear cells (U937), as demonstrated
      with a redox-sensitive fluorescent dye (2'7'-dichlorodihydrofluorescein [DCF]).
      Addition of L-histidine, and to a lesser extent D-histidine, to the culture media
      of U937 cells before LPS exposure, resulted in a significant dose-dependent
      reduction in LPS-induced intracellular DCF fluorescence, as measured
      quantitatively by flow cytometry. The potential therapeutic value of anti
      inflammatory drugs containing an L-histidine-like structure could protect
      infected mucosal tissues irrespective of microbial etiology.

PMID- 9605180
TI  - L-selectin(-/lo) and diabetogenic T cells are similarly distributed in
      prediabetic and diabetic nonobese diabetic mice.
AB  - We have previously shown that in the nonobese diabetic (NOD) mouse, an
      experimental model for autoimmune insulin-dependent diabetes, spleen diabetogenic
      T cells are contained within the T-cell subpopulation that express no or low
      levels of L-selectin. This phenotype characterizes activated/memory T cells. In
      the present study, we have compared the distribution of autoreactive T cells to
      that of L-selectin -/lo T cells in prediabetic and diabetic mice.
      Activated/memory T cells were found in decreasing concentrations in the bone
      marrow (BM), spleen, peritoneum, lymph nodes, and blood. This distribution
      correlated perfectly with that of T cells capable of transferring diabetes into
      syngeneic nondiabetic recipients. In diabetic mice, the highest levels of
      diabetogenic cells were observed in the spleen and BM. The peritoneum and lymph
      nodes contained intermediate frequencies of autoreactive cells. In the peripheral
      blood, the number of autoreactive T cells was variable, usually low; in some
      cases, they were undetectable. These cells were rare in the thymus. Diabetes
      transferring cells were present in the spleen and BM of prediabetic mice. In
      these animals, diabetogenic cells were present in the blood circulation with
      frequencies higher than in diabetic mice, suggesting that after disease onset,
      when almost all target beta cells have disappeared, the recirculation of
      autoreactive cells is greatly decreased and finally stops. These observations:
      (a) suggest that T cells from BM of prediabetic and diabetic patients may be a
      better source of diabetogenic cells than the blood for analyzing diabetes
      associated responses or for generating diabetogenic T-cell clones, and (b) point
      up the risk of using healthy autoimmune-prone donors for BM transplantation.

PMID- 9605182
TI  - Alleviation of monocrotaline-induced pulmonary hypertension by antibodies to
      monocyte chemotactic and activating factor/monocyte chemoattractant protein-1.
AB  - Administration of monocrotaline (MCT) causes pulmonary vascular lesions
      consisting of monocyte/macrophage infiltration in the early phase and medial
      thickening in pulmonary arteries and arterioles associated with pulmonary
      hypertension (PH) in the later phase. However, the molecular mechanism of
      monocyte/macrophage infiltration and its roles remain elusive. Herein, we have
      evaluated the role of a potent monocyte chemotactic and activating
      chemokine/monocyte chemoattractant protein-1 (MCAF/MCP-1) in MCT-induced PH in
      rats. A single injection of MCT induced PH at Day 21, as evidenced by increases
      in the ratio of right ventricular to left ventricular and septum weights
      (RV/LV+S) and right ventricular systolic pressure (RVSP). A significant increase
      in macrophage number in lungs started at Day 14, reaching a maximum at Day 21.
      MCAF/MCP-1 levels in bronchoalveolar lavage fluids were elevated significantly at
      Day 14 and remained high until Day 28, whereas plasma MCAF/MCP-1 levels increased
      at Day 7, returning to normal levels by Day 21. Immunoreactive MCAF/MCP-1
      proteins were mainly detected in macrophages in alveoli and in perivascular
      regions of pulmonary arterioles and venules. Intravenous administration of anti
      MCAF/MCP-1 antibodies with MCT significantly decreased macrophage infiltration
      and eventually reduced the increases in RV/LV+S and RVSP, as well as medial
      thickening of pulmonary arterioles. Thus, MCAF/MCP-1 is essentially involved in
      MCT-induced PH by recruiting and activating macrophages.

PMID- 9605183
TI  - Platelet endothelial cell adhesion molecule-1 expression modulates endothelial
      cell migration in vitro.
AB  - Endothelial cell migration is an important process that occurs during embryonic
      vasculogenesis and angiogenesis, wound healing, and tumor growth and metastasis,
      and after denudation injury following angioplasty and bypass grafting. Mechanisms
      regulating this process involve a complex interplay of cytoskeletal
      reorganization, cell-cell adhesion, and cell-extracellular matrix interactions.
      Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) is constitutively
      expressed in endothelial cells, leukocytes, monocytes, lymphocytes, and
      platelets. PECAM-1 undergoes dynamic dephosphorylation during endothelial cell
      migration in vitro and during vasculogenesis in the murine conceptus. In
      transfected 3T3 cells, in cultured endothelial cells, and in the murine conceptus
      undergoing vasculogenesis, the tyrosine phosphorylation state of PECAM-1 Y686
      correlates with the migratory state of the cells. In the present study, we
      investigate the role of PECAM-1 in modulating endothelial cell migration in vitro
      using retroviral transduction of c-myc epitope-tagged, wild-type, Y686 to F
      mutated PECAM-1 and extracellular domain-deleted PECAM-1 constructs in
      endothelial cells devoid of endogenous PECAM-1 (ECV304 cells) and in endothelial
      cells expressing high levels of endogenous PECAM-1 (bovine aortic endothelial
      cells, BAEC). In ECV304 cells, the expression of wild-type PECAM-1 inhibited
      migration rates, whereas in BAEC, overexpression of wild-type PECAM-1 had no
      effect. Expression of Y686 to F-mutated PECAM-1 or extracellular domain-deleted
      PECAM-1 in BAEC increased migration rates. These data support the concept that
      endothelial cell migration is modulated, in part, by a balance between PECAM-1
      cytoplasmic domain-mediated "inside-out" and "outside-out" signaling resulting
      from PECAM-1-mediated cell-cell interactions and integrin-extracellular matrix
      interactions.

PMID- 9605181
TI  - Analysis of the cytokine network among tumor necrosis factor alpha, interleukin
      1beta, interleukin-8, and interleukin-1 receptor antagonist in monosodium urate
      crystal-induced rabbit arthritis.
AB  - In the present study, we analyzed the cytokine network among TNFalpha, IL-1beta,
      IL-8, and IL-1 receptor antagonist (IL-1Ra) in a rabbit experimental model of
      acute gout. The production of TNFalpha in synovial fluids reached the peak at 2
      hours after the intra-articular injection of monosodium urate (MSU) crystals. The
      production of IL-1beta and IL-8 reached the first peak at 2 hours and the second
      peak at 9 and 12 hours, respectively. The production of endogenous IL-1Ra reached
      the peak at 9 hours. The source of TNFalpha and the first phase of IL-8 was
      synovial cells, whereas infiltrating leukocytes were the source of the second
      phase of IL-8 and also of IL-1beta and IL-1Ra. The production of TNFalpha was not
      altered by either anti-lL-8 IgG or IL-1Ra. The first IL-1beta peak was reduced
      only with a combination of anti-TNFalpha mAb and anti-lL-8 IgG, whereas the
      second peak was significantly reduced by either inhibitor. The first IL-8 peak
      was not altered with anti-TNFalpha mAb or IL-1 Ra, whereas the second IL-8 peak
      was reduced with IL-1Ra. Anti-TNFalpha mAb or anti-lL-8 IgG significantly reduced
      the peak level of endogenous IL-1Ra. These cytokine inhibitors also attenuated
      the maximal leukocyte accumulation at 9 hours, but not the initial phase, which
      occurred within 2 hours. These results provide evidence that IL-8 and TNFalpha
      were responsible for the production of IL-1beta and IL-1Ra, and that IL-1beta was
      responsible for the second phase of IL-1beta and IL-8 production. Our data also
      suggest that the initial and the maximal phases of leukocyte influx are
      differently regulated. Finally, the intravenous injection of colchicine inhibited
      neutrophil infiltration without affecting the production of TNFalpha or the first
      peak of IL-8, suggesting that colchicine inhibits MSU crystal-induced arthritis
      by directly inhibiting the migration of neutrophils.

PMID- 9605179
TI  - Immune response against human primary malignant melanoma: a distinct cytokine
      mRNA profile associated with spontaneous regression.
AB  - Spontaneous regression of melanoma lesions is thought to be the result of an
      efficient immune response against melanoma cells in vivo. The outcome of immune
      responses is critically influenced by a complex network of interacting cytokines
      present in the local microenvironment. Analysis of cytokine gene transcription in
      melanoma lesions exhibiting or lacking a sufficient anti-tumor immune response
      thus may help to define cytokines or cytokine combinations critical to the
      development of this immune response. In the present study, we have investigated
      an extended panel of cytokine and cytokine receptor genes by reverse
      transcription-PCR and in situ hybridization in regressive and progressive primary
      human cutaneous melanoma samples. Whereas the presence of a lymphocyte infiltrate
      in tissue samples was associated with a TH1 cytokine mRNA profile (TNF-alpha, INF
      gamma, IL12p35, IL12p40, IL2Rbeta, and IL2Rgamma), clinically and histologically
      regressive samples exhibited additionally increased transcript levels for GM-CSF,
      IL2, and IL15. mRNAs of TH2 cytokines IL4 and IL5 were detected only in a minor
      portion of progressive melanoma samples and regressive melanoma lesions. These
      results were further supported by comparison of progressive with regressive
      regions in three melanoma samples. Again, regressive regions contained higher
      transcript levels for GM-CSF, IL2, and IL15. In comparison to cutaneous
      metastatic melanoma lesions, regressive melanomas also overexpressed the same
      cytokine mRNA profile. These results provide evidence for an association of
      spontaneous regression with increased transcript levels for the cytokine
      combination GM-CSF, IL2, and IL15 in malignant melanoma. This cytokine
      combination could be relevant for experimental anti-tumor immune response studies
      and for immunotherapeutic and gene transfer studies in the treatment of melanoma
      patients.

PMID- 9605184
TI  - The interleukin-4/interleukin-13 receptor of human synovial fibroblasts:
      overexpression of the nonsignaling interleukin-13 receptor alpha2.
AB  - Interleukin (IL)-4 and IL-13 are known to bind to shared heteromultimeric
      receptor complexes of variable composition. Given the many regulatory effects of
      IL-4 and IL-13 on synovial cells, we aimed to characterize their IL-4/IL-13
      receptor (R). Cultivated synovial fibroblasts expressed transcripts for IL
      4Ralpha and IL-13Ralpha1, the human homolog of the recently cloned mouse IL-13R,
      but not the common gamma-chain of the IL-2R. In particular, IL-13Ralpha2 mRNA,
      encoding a different IL-13R recently cloned from human renal carcinoma cells, was
      expressed at a strikingly high level. Correspondingly, a predominant protein
      migrating at 65 to 75 kd was cross-linked by iodinated IL-13 and was not cross
      competed by an excess of unlabeled IL-4. However, by flow cytofluorometry, IL
      13Ralpha1 (detected by the anti-lL-13Ralpha1 mAb 65) and IL-4Ralpha (detected by
      the mAb S697) were expressed at similar low density. Radioligand binding studies
      revealed for both cytokines approximately 300 receptors/cell with similar high
      affinity. An additional class of IL-13Rs was identified after occupation of the
      shared high-affinity receptors by the nonsignaling, double-mutant IL-4121R-->D,
      124Y-->D (RY-IL-4). In these experiments, 1251-IL-13 bound to a single receptor
      population with a Kd of approximately 300 pM and approximately 5000 sites/cell,
      matching the published affinity of monomeric IL-13Ralpha2 when expressed in COS7
      cells. RY-IL-4 blocked the IL-4- and IL-13-mediated vascular cell adhesion
      molecule (VCAM)-1 expression and Stat6 activation, suggesting that the large
      number of high-affinity IL-13Ralpha2 monomers are silent receptors, likely
      representing a decoy target for IL-13.

PMID- 9605186
TI  - Immunohistochemical analysis of the T-cell receptor beta-chain variable regions
      expressed by T lymphocytes infiltrating primary human melanoma.
AB  - The T-cell receptor beta-chain variable (TCRBV) region repertoire expressed by
      tumor-infiltrating lymphocytes was characterized by immunohistochemical analysis
      using a panel of 18 monoclonal antibodies on cryosectioned specimens of 14
      primary vertical growth phase (VGP) melanomas with a T-cell infiltrate
      histopathologically defined as brisk or nonbrisk. T lymphocytes present in the
      VGP of all patients displayed a restricted T-cell receptor usage, with a pattern
      of reactivity similar in brisk versus nonbrisk infiltrates. No evidence of
      restriction was found in the extra-VGP lymphocytic infiltrates, when available,
      within the same specimen. Furthermore, the repertoire of TCRBV expressed in nodal
      metastases was similar to that of the corresponding primary melanomas in the two
      cases tested. The results obtained by this in situ analysis indicate that the
      TCRBV repertoire in VGP is determined by a preferential migration of T
      lymphocytes, possibly indicative of an immune response to melanoma-associated
      antigens.

PMID- 9605185
TI  - A monocyte chemotactic factor, S19 ribosomal protein dimer, in phagocytic
      clearance of apoptotic cells.
AB  - HL-60 cells derived from a human promyelocytic leukemia underwent apoptosis by
      heat treatment. When the heat-treated HL-60 cells were injected into guinea pig
      skin, monocyte/macrophage infiltration was observed 24 or 36 hours later, and the
      apoptotic cells were phagocytically cleared by 48 hours after their injection.
      The infiltration and clearance patterns were quite different from those observed
      in injection of necrotic or boil-fixed HL-60 cells. The apoptotic cells released
      a monocyte chemotactic factor in vitro 24 hours after the heat treatment. The
      chemotactic factor generated was identified as the cross-linked homodimer of S19
      ribosomal protein by its immunologic and physicochemical properties. A serine
      protease that inactivates the monocyte chemotactic factor was also released from
      the apoptotic cells 30 hours after the heat treatment. A super infusion of this
      protease into the skin where the apoptotic cells had been injected diminished the
      number of infiltrated monocytes. The present results indicate an important role
      of the S19 ribosomal protein dimer in the phagocytic clearance of apoptotic
      cells.

PMID- 9605189
TI  - Allele-specific-polymerase chain reaction: a novel method for investigation of
      the imprinted insulin-like growth factor II gene.

PMID- 9605188
TI  - A functional assay for intercellular, junctional communication in cultured human
      lung carcinoma cells.

PMID- 9605190
TI  - Immunohistochemical detection of the DNA repair enzyme O6-methylguanine-DNA
      methyltransferase in formalin-fixed, paraffin-embedded astrocytomas.

PMID- 9605187
TI  - Different susceptibility of mice to immune-mediated cholangitis induced by
      immunization with carbonic anhydrase II.
AB  - Carbonic anhydrase II (CA-II), an enzyme that catalyzes hydration of carbon
      dioxide to bicarbonate and hydrogen ions, is located exclusively in
      cholangiocytes in the liver. Recently, patients with autoimmune cholangitis have
      been reported to have serum antibodies to CA-II. Moreover, active immunization of
      susceptible mice with CA-II results in inflammation of submandibular glands,
      where CA-II is also expressed. In the present study, we attempted to produce
      cholangitis by immunization with CA-II using two strains of mice with different
      potential susceptibilities. Balb/c and DBA/1J mice were immunized with a dose of
      human CA-II (100 microg) intraperitoneally every other week on three occasions.
      One week after the final immunization, mice were killed and blood and tissue
      samples harvested. Light and electron microscopic evaluation for inflammation was
      performed under coded identification. After immunization of Balb/c mice, numerous
      mononuclear cells, mostly CD4-positive T cells, appeared around bile ducts;
      lymphocyte invasion between cholangiocytes was also seen. Inflammation was not
      observed outside the liver. Morphologic evidence of cholangitis was observed in 8
      (53.3%) of 15 Balb/c mice and in 3 (20%) of 15 DBA/1 J mice. In the control mice
      immunized with bovine serum albumin (BSA), cholangitis was observed in only 1
      (6.7%) of 15 Balb/c mice and none of 15 DBA/1J mice. Balb/c mice immunized with
      CA-II had statistically significant cholangitis compared with those immunized
      with BSA (p < 0.01), whereas DBA/1J did not show a significant difference from
      controls. Balb/c mice immunized with CA-II showed specific antibody production
      after immunization, whereas DBA/1J mice immunized with CA-II had anti-CA-II
      antibody even in preimmune sera. Adoptive transfer of splenocytes from CA-II
      immunized Balb/c mice resulted in cholangitis in two (66.7%) of three Balb/c
      recipients. These data strongly suggest that the cholangitis can be induced by CA
      II immunization in susceptible strains of mice.

PMID- 9605191
TI  - Lessons on learning.

PMID- 9605192
TI  - Differences in clinical experiences of ADN and BSN students.
AB  - Prior research has suggested that clinical experience for nursing students is
      stressful. Concern about making an error and harming the patient, limited
      knowledge and skills for practice, and difficulties in interacting with the
      teacher and others in the clinical setting are some of the stressors reported by
      students. Few studies have compared these stresses and the clinical experiences
      in general between students in associate degree (ADN) and baccalaureate (BSN)
      nursing programs. The purposes of this research were to compare the clinical
      experiences of ADN and BSN students at different levels in the programs and
      describe these experiences from the students' perspectives. As such, both
      quantitative and qualitative data were collected from 415 students in ADN and BSN
      programs in the Midwest. The ADN students reported significantly higher stress in
      clinical practice than BSN students (t = 2.16, p < .05). The stress experienced
      by ADN and BSN students in clinical practice increased as they progressed through
      the programs. The semester prior to graduation was the most stressful time in
      terms of clinical practice for both ADN and BSN students. The instructor was the
      predominant stressor reported by students in ADN programs across all levels of
      the curriculum. Among BSN students, the most prevalent stresses were coping with
      demands associated with patient care and the clinical teacher. The findings
      highlight the important role of the clinical faculty in both types of nursing
      programs.

PMID- 9605194
TI  - Portfolio: authentic assessment in the age of the curriculum revolution.
AB  - This article provides an extensive review of the literature on portfolio use in
      education. There is a gap in the literature related to portfolio use in nursing
      education. Portfolios are one method of authentic assessment, showing evidence of
      student growth and achievement over time. Development of the student portfolio
      promotes collaboration between student and faculty. The Integrated Proficiency
      Criterion (IPC) framework is one proposed method for portfolio development and
      evaluation, using Benner's stages of proficiency and NLN criteria for
      accreditation of baccalaureate nursing programs.

PMID- 9605193
TI  - Development of an instrument to measure caring peer group interactions.
AB  - The purpose of this study was to develop psychometric properties of the Peer
      Group Caring Interaction Scale (PGCIS) designed to measure caring during informal
      peer interactions as experienced by undergraduate nursing students. The PGCIS has
      two subscales that address caring peer behaviors and interactional events during
      which students assist their peers in the resolution of specific needs. PGCIS
      psychometric properties were developed using data from 873 junior students
      enrolled at 87 BSN schools of nursing. Internal consistency reliability was
      demonstrated for the 9-item Caring Behaviors and the 7-item Giving Assistance
      subscales with a coefficient alpha of .91 for each. Findings from an exploratory
      factor analysis supported the two subscale structure of the PGCIS. The PGCIS
      scores correlated positively with scores on the Intimacy subscale of the
      Organization Climate Description Questionnaire (OCDQ) and the Peer Group
      Interaction Scale and inversely with scores on the OCDQ Disengagement subscale.
      The findings from this study provide beginning support for the PCGIS as a valid
      and reliable approach to the measurement of caring in academic settings.
      Additional studies are recommended to continue the psychometric evaluation of
      this instrument.

PMID- 9605195
TI  - The reticent student: implications for nurse educators.
AB  - Nursing education has recently begun to shift to a more emancipatory learning
      format. In accord with Freire, many nursing classrooms currently use dialogical
      teaching approaches as an integral part of the education process. There are many
      students unable to share in the process of dialogue because of reticence.
      Reticence is a personality quality in which a person is reluctant to speak. While
      dialogue appears to be a way to promote learning and is intended to result in
      emancipation for students, it may result in subjugation for the shy, reticent
      student. The literature does not provide information regarding the impact of
      reticence on the student in higher education, particularly the student in a
      professional program. This article discusses the impact of reticence on the
      learning experiences of nursing students and the effects of classroom dynamics
      and teaching methodologies used with nursing students.

PMID- 9605196
TI  - Clinical placement and correlates affecting student attitudes toward the elderly.

PMID- 9605197
TI  - Students' philosophical assumptions and psychology in the classroom.
AB  - The current study investigated the underlying philosophical assumptions, or world
      views, that undergraduate nursing students bring to the psychology classroom. It
      was hypothesized that students would most prefer mechanistic explanations of
      behavior, explanations derived from an analytical, linear, cause-and-effect
      model. It was also hypothesized that they would least prefer contextualistic
      explanations of behavior, i.e., explanations derived from a synthetic,
      subjective, and relational model. Forty female hospital-based RN students
      completed a modified version of the World Hypothesis Scale. As predicted, they
      were significantly more likely to endorse mechanistic explanations and less
      likely to endorse contextualistic explanations. Because teaching psychology lends
      itself to a contextualistic approach in which a variety of models for
      understanding behavior are explored, the study of psychology can be one way to
      increase nursing students' critical thinking skills.

PMID- 9605199
TI  - Integrating self-care into nursing education.
AB  - The didactic and clinical components of the mental health curriculum content
      within a school of nursing in the southeastern United States were revised to
      integrate a self-care focus. The major learning modalities used were group
      process dynamics and a structured psychoeducation approach. A six-hour per
      quarter credit course was divided into three parts: theory, laboratory, and
      clinical. Students averaged 3 hours in class, 2 hours in a simulated college
      laboratory, and 7 hours at a clinical site per week for one quarter. Theoretical
      concepts were taught during class time; self-care activities and concepts were
      taught in the college laboratory; and clinical time was devoted to practicing
      self-care through patient-nurse interactions and group work. Nurse educators may
      use this study to guide curriculum development in fostering caring models of
      nursing education.

PMID- 9605198
TI  - Recognizing a post-traumatic stress disorder in a nursing student.

PMID- 9605200
TI  - Experiential learning of clinical skills by beginning nursing students:
      "coaching" project by fourth-year student interns.
AB  - To fulfill the requirements for the internship program, fourth-year academic
      nursing students participated in a leadership program and became coaches for
      novice students who were beginning their first clinical rotations in the
      hospital. The concept of coaching is recognized in theory, research, and clinical
      education as an educational tool, which provides mutual benefits for the coachee
      and the coach. The project lasted 12 weeks, 2 clinical days per week. The coaches
      served as a source of support and knowledge and assisted in problem solving for
      the beginning students. As nurse educators who oversaw the project, the authors
      summarized the program as it was developed and implemented at the Assaf HaRofeh
      School of Nursing including problems, revisions, and final conclusions and
      discussion.

PMID- 9605201
TI  - Improving nursing education classroom environments.
AB  - This study describes the first use of a classroom environment questionnaire with
      a class in nursing education. An instructor of nursing students monitored classes
      using such a questionnaire. The questionnaire used was the College and University
      Classroom Environment Inventory and it was used to obtain practical and useful
      information about the learning environment in two different classes.
      Collaborative changes were made in the classes to improve the classroom
      environment and consequently the learning situation. Any instructor of nursing
      students could use this same process with this instrument.

PMID- 9605202
TI  - International Symposium on Lycopene and Tomato Products in Disease Prevention: an
      introduction.

PMID- 9605203
TI  - Overview of lycopene, carotenoids, and disease prevention.

PMID- 9605204
TI  - Nutrient content of tomatoes and tomato products.
AB  - During the last half-century, the fruit of the cultivated tomato (Lycopersicon
      esculentum), commonly considered a vegetable, has become a popular and highly
      consumed food in the United States. Production of tomatoes in the United States
      ranks second only to potatoes. As a consequence, tomatoes and tomato-based foods
      provide a convenient matrix by which nutrients and other health-related food
      components can be supplied to human beings. Tomatoes and tomato products are rich
      sources of folate, vitamin C, and potassium. Relative to phytonutrients, the most
      abundant in tomatoes are the carotenoids. Lycopene is the most prominent
      carotenoid followed by beta-carotene, gamma-carotene and phytoene as well as
      several minor carotenoids. The antioxidant activity of lycopene as well as
      several other carotenoids and their abundance in tomatoes makes these foods rich
      sources of antioxidant activity. The provitamin A activity of beta- and gamma
      carotene, their modest levels in tomato products, and the high consumption of
      these foods results in a rich supply of vitamin A activity from tomato-based
      foods. Tomatoes also contain several other components that are beneficial to
      health, including vitamin E, trace elements, flavonoids, phytosterols, and
      several water-soluble vitamins.

PMID- 9605205
TI  - Lycopene stability during food processing.
AB  - Accumulating epidemiological evidence continues to show that lycopene, found in
      tomatoes, grapefruits and watermelons, is associated with a reduced risk of
      developing certain chronic diseases and cancers. With respect to lycopene in
      tomato products, the effect of thermal processing on its stability has not yet
      been rigorously addressed. This paper assesses the effect of several different
      heat treatments on lycopene's isomeric distribution in a variety of tomato
      products, as well as in organic solvent mixtures containing all-trans lycopene.
      Experimental results indicate that in contrast to beta-carotene, lycopene
      remained relatively resistant to heat-induced geometrical conversion during
      typical food processing of tomatoes and related products. The presence of fat,
      the change in percentage of solids, and the severity of heat treatment were not
      contributing factors in the formation of lycopene isomers in tomato products,
      except at extreme conditions not regularly employed in the food industry or
      during food preparation. However, lycopene in organic solvent isomerized readily
      as a function of time even in the absence of light and the presence of
      antioxidants. These findings suggest that while lycopene is stable in the tomato
      matrix, sample handling techniques should be carefully evaluated to minimize the
      formation of lycopene cis isomers in organic solutions.

PMID- 9605206
TI  - Factors influencing the uptake and absorption of carotenoids.

PMID- 9605207
TI  - Lycopene uptake and tissue disposition in male and female rats.
AB  - Epidemiologic and clinical studies suggest that tomato consumption may reduce the
      risk of cancer. Lycopene, a hydrocarbon carotenoid, is the major carotenoid in
      tomatoes and, as a potent singlet oxygen quencher, has been considered by some to
      be the biologically active agent responsible for the reduction of cancer risk
      associated with tomato consumption. However, little is known concerning lycopene
      absorption or biological activity in rodent models of cancer. Therefore, the
      present study was designed to provide information regarding the uptake and tissue
      disposition of lycopene and related carotenoid after feeding a diet containing a
      carotenoid mixture extracted from tomatoes (Betatene). Betatene was added to the
      diet at 2.3, 0.9, 0.45, 0.23, 0.09 and 0 (mM/kg diet) and fed to male and female
      Fischer-344 rats for a period of 10 weeks. Using reverse phase HPLC methods, it
      was found that approximately 55% of administered lycopene was excreted in the
      feces. In both males and females, lycopene concentrations were highest in the
      liver (120-42 microg/g wet wt.); physiologically significant levels were detected
      in prostate (97-47 ng/g), lung (227-134 ng/g), mammary gland (309-174 ng/g) and
      serum (285-160 ng/ml). Tissue concentrations were related to dose with the
      exception of serum, and differences between males and females were minimal. Other
      carotenoids present in Betatene (i.e., phytoene, phytofluene, z-carotene and beta
      carotene) were also absorbed and stored in the liver. These results indicate that
      lycopene, when incorporated into the semipurified AIN-76A diet, is absorbed in
      both male and female rats in a dose-related manner and can be detected at
      nanogram levels in a variety of target organs.

PMID- 9605208
TI  - Human studies on bioavailability and plasma response of lycopene.

PMID- 9605209
TI  - Lycopene: antioxidant and biological effects and its bioavailability in the
      human.
AB  - Lycopene is a non-provitamin A carotenoid present in human blood and tissues. The
      major dietary sources of lycopene for the human are tomatoes and tomato products.
      Protective effects of a lycopene-rich diet on some types of cancer were suggested
      on the basis of epidemiological studies. There are several biochemical mechanisms
      potentially underlying the protective effects of lycopene. These include
      antioxidant activity such as the quenching of singlet oxygen and the scavenging
      of peroxyl radicals, induction of cell-cell communication, and growth control. In
      vitro and in vivo studies support this assumption. Dietary lycopene is absorbed
      and distributed in the human organism, but its bioavailability depends on various
      factors such as food processing or coingestion of fat. Little is known about the
      metabolism of lycopene. Potentially biologically active oxidation products of
      lycopene have been identified in human plasma.

PMID- 9605210
TI  - Mediterranean epidemiological evidence on tomatoes and the prevention of
      digestive-tract cancers.
AB  - Tomatoes have been estimated as the second most important source of vitamin C,
      after oranges, in an Italian population. We have therefore considered the
      relationship between tomato intake and the risk of digestive tract cancers using
      data from a series of case-control studies conducted in Italy between 1983 and
      1992, and including 317 histologically confirmed, incident cases of cancer of the
      oral cavity and pharynx, 85 of the esophagus, 723 of the stomach, 955 of the
      colon, and 629 of the rectum, and a total of 2879 controls admitted for acute,
      non-neoplastic conditions, unrelated to long-term modifications of diet.
      Multivariate odds ratios (OR) and 95% confidence intervals (CI) for subsequent
      quartiles of intake of tomatoes were derived, after allowance for age, sex, study
      center, education, smoking, alcohol drinking, and total calorie intake. There was
      a consistent pattern of protection for all sites. The ORs for the highest
      consumption quartile were 0.65 (95% CI 0.4-1.0) for oral cavity, pharynx, and
      esophagus, 0.43 (95% CI 0.3-0.6) for stomach, 0.39 (95% CI 0.3-0.5) for colon,
      and 0.42 (95% CI 0.3-0.6) for rectum. Another study of colorectal cancer, based
      on 1,953 cases and 4,154 controls, conducted between 1992 and 1996 and using a
      more detailed food frequency questionnaire, confirmed that tomato intake was
      significantly protective on colorectal cancer risk, even after allowance for
      several potential confounding factors, including measures of body mass index,
      calorie intake, and physical activity. The ORs for the highest consumption
      quintile were 0.79 (95% CI 0.6-0.9) for colon, and 0.71 (95% CI 0.5-0.9) for
      rectal cancer. The beneficial effect of tomatoes observed in these
      epidemiological studies may be due to the fact that they constitute one of the
      most specific features of the Mediterranean diet. This has both a scientific and
      a public health relevance.

PMID- 9605211
TI  - Tomatoes, lycopene, and prostate cancer.

PMID- 9605212
TI  - Evaluation of the evidence on the role of tomato products in disease prevention.
AB  - During the last 30 years, research in the field of nutrition and chronic disease
      causation has led to exciting, significant progress in providing an understanding
      of specific risk factors and chemopreventive agents. The major health problems
      considered are cardiovascular diseases and the nutritionally linked cancers,
      including those in the stomach, colon, breast, prostate, ovary, and endometrium.
      The major elements considered were salt, type and amount of fat, and heterocyclic
      amines formed during cooking. Bran cereal fiber, as well as vegetables, fruits,
      and tea have been shown to inhibit the complex processes of initiation and
      development of these diseases. One aspect involved in initiation and development
      of both cardiovascular diseases and the cancers noted are abnormal oxidative
      processes leading to the generation of hydroxy radicals and peroxy compounds. In
      part, the protective role of vegetables, fruits, and tea is to provide
      antioxidant vitamins and specific polyphenols that display a powerful inhibition
      in oxidative reactions. Epidemiological studies as well as laboratory
      experimentation have yielded sound data and evidence in support of the fact that
      vegetables, fruits, and tea and specific antioxidants therein account
      mechanistically for inhibition. Geographic pathology has provided important data
      that populations with a regular intake of tomato products, such as in the
      Mediterranean region, have a lower incidence of the chronic diseases noted. The
      current Symposium is considering the varied mechanisms of action of tomato
      products in general, and one of the active principles, lycopene. Cooking is a
      factor in releasing the desirable antioxidants from tomatoes. Cooked tomato
      products may be preferable to the raw vegetable or juices derived from tomatoes
      bearing on absorption of the active principles. Optimally, absorption of
      lycopene, a highly lipid-soluble chemical, is improved in the presence of a
      small, but essential amount of oil or fat. Research in the field of nutrition and
      health has shown that monounsaturated oils such as olive oil or canola oil are
      most desirable, since such oils do not increase the risk of atherosclerosis,
      coronary heart disease, or the nutritionally linked cancers. The International
      Symposium on tea conducted in 1991 has provided worldwide interest in research on
      the beneficial effects of tea. It is now hoped that the present Symposium,
      dealing with another inexpensive and readily available food, tomatoes, will
      enhance interest in and funding for additional research, to underwrite future
      recommendations for possibly enhanced production and use of tomato-derived
      nutritional elements, with the goal of application to the prevention of major
      chronic diseases, the treatment of which is costly and often ineffective.

PMID- 9605213
TI  - A.J. Ladman: managing editor of The Anatomical Record, 1968-1998.
AB  - In the period 1906-1998, The Anatomical Record has had only six managing editors.
      One of these individuals, A.J. Ladman, served in this capacity for 30 years,
      almost a full third of the history of this journal up to 1998. Ladman received
      his Ph.D. degree from Indiana University in 1952, was at Harvard for 9 years
      (1952-1961) and at the University of Tennessee from 1961-1964. He became
      professor and chairman of the Department of Anatomy at the University of New
      Mexico School of Medicine in 1964. In April 1968, Ladman was appointed managing
      editor of The Anatomical Record by the American Association of Anatomists (AAA).
      He brought energy and innovative ideas to the journal and would apply those in
      the changes he instituted over the years of his tenure. In April 1998, after 30
      years of exemplary service to this journal and to the AAA, Ladman passed the
      responsibility on to Roger Markwald. During his career, and in addition to his
      editor's work, he conducted research on an impressively wide range of topics,
      served as an elected officer in several professional organizations, and was
      founding chair of anatomy at New Mexico. He went to Hahnemann in 1981, served as
      Dean of the School of Allied Health Professions (1981-1986), and is currently
      adjunct professor of neurobiology and anatomy. The AAA expresses its sincere
      appreciation to A.J. Ladman for his excellent stewardship of The Anatominal
      Reord.

PMID- 9605215
TI  - Spinal segment range of motion as a function of in vitro test conditions: effects
      of exposure period, accumulated cycles, angular-deformation rate, and moisture
      condition.
AB  - BACKGROUND: The purpose of this study was to thoroughly evaluate the relationship
      of possible mechanical and environmental conditions in the testing of spinal
      joint segments, including ambient-temperature exposure, accumulated test cycles,
      angular-deformation rate, and moisture condition on the motion characteristics of
      joints, with the example of isolated spinal segments. METHODS: In one test,
      controlled loading was applied to six motion segments every 8 hours in each of
      the primary anatomical directions while moisture was held constant. In a second
      test, 18 specimens were divided equally into moisture-static, air-exposed, and
      slowly irrigated groups and loaded to 500 cycles. In a third test, a similar
      sample was tested over a range of angular-deformation rates (0.6-5.1
      degrees/second). RESULTS: Range of motion (ROM) increased steadily with ambient
      temperature exposure time, resulting in a 10% change at about 20 hours but was
      most stable in the moisture-static group over both accumulated load cycles and
      loading rate changes. CONCLUSIONS: The most critical factor for functional
      testing of spinal segments appears to be length of exposure.

PMID- 9605214
TI  - Altered expression of glutamate transporter GLAST mRNA in rat brain after
      photochemically induced focal ischemia.
AB  - BACKGROUND: The neurotransmitter glutamate is involved in fast excitatory
      synaptic transmission in the mammalian brain. Glutamate released from presynaptic
      terminals must be removed rapidly from the synaptic cleft by high affinity,
      sodium-dependent glutamate transporters to keep the extracellular glutamate
      concentration low to protect neuron from glutamate excitotoxicity, which is the
      major pathological mechanism of brain ischemia. GLAST is one of the identified
      four subtypes of the glutamate transporter system and has been suggested to play
      an important role in some pathological conditions. But until recently, very
      little information existed the concerning relationship between GLAST expression
      and cerebral ischemia. METHODS: Nonradioactive in situ hybridization was employed
      to evaluate the changes of glutamate transporter GLAST mRNA expression in rat
      cerebral cortex and hippocampus following photochemically induced focal cortical
      ischemia. RESULTS: GLAST mRNA expression in cerebral pyramid cells below the
      infarcted area did not change at 3 h, significantly decreased at 12 h, recovered
      to the control level at 24 h, and significantly increased at 72 h following the
      ischemic lesion. No changes in GLAST mRNA expression were observed in all
      subfields of the hippocampal complex. CONCLUSIONS: The present findings suggest
      that the time-course changes of GLAST mRNA expression after ischemia may be
      correlated with the pathogenesis of photosensitive ischemic brain damage.

PMID- 9605216
TI  - M. levator ani in the rat: does it really lift the anus?
AB  - BACKGROUND: There is a good deal of confusion about the denomination of the
      pelvic floor muscles of the rat in the literature. By carefully dissecting and
      observing tail and visceral movements and pressure measurements in the vagina,
      rectum, and urethra during electrical stimulation, we studied the anatomy and
      function of the different muscles and searched for similarities with the human
      anatomy. RESULTS: We found some degree of similarity between the M. pubococcygeus
      and M. iliococcygeus muscles in both species. The M. levator ani in the rat
      resembles in gross anatomy the M. puborectalis in man, but the insertion and
      function are different. More specifically, stimulation of the M. levator ani led
      to only a negligible pressure rise in the rectum and no lifting of the rectum or
      anus. CONCLUSIONS: The M. pubococcygeus and the M. iliococcygeus share
      similarities with their homologues in the human. The M. levator ani, which is
      present only in the male rat, reveals some anatomical resemblance with the human
      M. puborectalis but has a different insertion and function. Because it does not
      lift the anus during contraction, its denomination as M. levator ani seems
      unjustified. Because of its principal sexual function, its fixation to the
      bulbus, and its sensitivity to testosterone, naming this muscle M.
      bulbocavernosus dorsalis would indeed seem more logical.

PMID- 9605217
TI  - Articular cartilage collagen birefringence is altered concurrent with changes in
      proteoglycan synthesis during dynamic in vitro loading.
AB  - INTRODUCTION: The articular cartilage collagen network and proteoglycans are
      subject to changes in deteriorating joint diseases. In this study, we exposed
      articular cartilage plugs to cyclic loading and investigated the properties of
      collagen network and proteoglycans in different zones of the articular cartilage.
      METHODS: Articular cartilage full-depth plugs were exposed in vitro to 4.1 MPa
      cyclic (0.5 Hz) loading for 1 to 20 hr and investigated using quantitative
      microscopic methods (i.e., polarized light microscopy, microspectrophotometry,
      and autoradiography). RESULTS: The loading caused packing or condensation of the
      tissue. In histological sections, the height of uncalcified articular cartilage
      decreased by an average of 12.8% (range, 4 to 19.7%). Loading increased the
      birefringence of collagen in the superficial cartilage (P < 0.05), with
      thickening of the zone up to 41.4% at 20 hr. The thickness of the intermediate
      zone increased also (22% at 1 hr and 434% at 20 hr). Concomitantly, the
      birefringence (P < 0.05) and the thickness of the deep zone decreased (18.5 to
      27.8%). Loading for 4 hr increased the 35S-sulphate incorporation of the
      cartilage explants by an average of 67% (P < 0.05). The increase was most
      significant in the deep cartilage. A simultaneous increase was observed in the
      proteoglycan concentration of the cartilage; the staining intensity with safranin
      O increased by 8.8% (P < 0.05). After 8 hr loading, this stimulation decreased;
      at 20 hr, loading caused a clear inhibitory effect on proteoglycan synthesis in
      the superficial zone. DISCUSSION: According to these results, the chosen loading
      regimen increased the thickness and collagen orientation in the superficial zone.
      In contrast, the thickness and birefringence in the deep cartilage were reduced.
      The proteoglycan metabolism of chondrocytes was first stimulated deep in the
      cartilage, but as the loading continued, the effect proved to be inhibitory
      (especially in the superficial part of uncalcified cartilage).

PMID- 9605218
TI  - Effects of a low-protein diet on prolactin- and growth hormone-producing cells in
      the rat pituitary gland.
AB  - BACKGROUND: It is well known that an unbalanced diet induces various changes in
      the pituitary gland. However, little attention has been paid to the molecular
      aspects of this perturbation. We studied the influence of a low-protein diet
      (LPD) on the prolactin (PRL) and growth hormone (GH) cells in the rat pituitary
      gland using immunohistochemical staining and in situ hybridization. MATERIALS:
      Rats aged 20 days were fed a diet containing 27% protein or one with 8% protein
      (LPD) for 30 days. Pituitary glands were obtained and subjected to either
      immunohistochemistry or in situ hybridization. Quantitative morphological
      analysis was then conducted to determine cell number and area as well as the
      percentage of cells stained by the respective antisera and/or cDNA probe in each
      experimental group. RESULTS: The average sectional areas of both PRL- and GH
      producing cells in the LPD group were smaller in size than those in the controls.
      The cell numbers per unit area (mm2) of PRL-positive cells and PRL mRNA-positive
      cells were 3,596.5 and 3,948.6, respectively, in the LPD group, and 3,179.6 and
      4,888.5, respectively, in the controls. The numbers per unit area of GH-positive
      cells and GH mRNA-positive cells in the LPD group were similar (2,252.3 and
      2,224.4), as compared to 2,161.3 and 1,684.2, respectively, in the well-fed rats.
      Whereas PRL-positive cells comprised about 27% of the total number of cells in
      both animal groups, those given the LPD contained a lower percentage (29%) of PRL
      mRNA-positive cells as compared to the controls (44%). On the other hand, GH mRNA
      positive cells numbered about 15% of the total cell population both animal
      groups; however, the malnourished rats contained a lower percentage (16%) of GH
      positive cells than did their well-fed counterparts (20%). CONCLUSIONS: Taken
      together, these results indicate that in the rat pituitary gland, administration
      of an LPD reduced the size of PRL- and GH-positive cells as well as
      differentially affecting a subpopulation of the PRL mRNA-positive cells and the
      GH-positive cells.

PMID- 9605220
TI  - Morphometry of human coronary arterial trees.
AB  - BACKGROUND: Some groups, including ours, have been generating arterial tree
      models using constrained constructive optimization (CCO). Arterial trees have
      been grown to arbitrary resolution without input of anatomical data. We performed
      this study to learn about the shortcomings that might have resulted from
      neglecting the anatomical data in CCO models. METHODS: In a total of 450 segments
      obtained from 4 human cast hearts, the ratio ofbifurcating daughter segment radii
      (O < Sbif = r(2)/r(1) < 1) was examined, which corresponds to the split of the
      total flow of the mother segment. For any complete bifurcation, where the radii
      of the parent segments and the radii of daughters were known, the area expansion
      ratio was computed (Aexp = [r(1)2 + r(2)2]/r(parent)2). RESULTS: The bifurcating
      ratio was found to be distributed in a nonnormal fashion, with a median of 0.76.
      The average area expansion ratio Aexp, characterizing the change of cross
      sectional area of the vasculature from proximal to distal, was 0.93+/-0.26. The
      'rate of branching' (d(i)/(d(0)) was defined by the segment diameter relative to
      the diameter of the root segment. Averaging the rate of branching over segments
      within each bifurcation level resulted in a decreasing function of bifurcation
      level. CONCLUSIONS: This article provides new experimental data on branching
      geometry of coronary arteries (i.e., the trees evaluated in this study are purely
      delivering rather than conveying). Based on these facts, we suggest that the
      analytical bifurcation law in CCO might be replaced by the bifurcation rule
      obeyed on a stochastic basis only.

PMID- 9605219
TI  - Coordinated capillary and myocardial growth in response to thyroxine treatment.
AB  - BACKGROUND: Thyroid hormone-induced cardiac hypertrophy is a model of enhanced
      physiological growth and angiogenesis. This study addressed the growth and
      geometry of the capillary bed in relation to the development of cardiac
      hypertrophy. METHODS: Thyroxine was administered daily (0.2 mg/kg, s.c.) for 5 or
      10 days to Fischer 344 rats. After obtaining ventricular function and hemodynamic
      data, the hearts were perfuse fixed, and specimens from the left ventricle (LV)
      were subjected to image analysis to determine indices of capillary growth.
      RESULTS: After 5 days of treatment, prior to cardiac enlargement, capillary
      length density was significantly greater in the epimyocardium of the thyroxine
      rats than in the controls (saline injected). Most of the increase could be
      attributed to an increase in capillary numerical density, but some enhancement in
      capillary profile axial ratio suggests that enhanced tortuosity or formation of
      oblique channels also occurred. After 10 days of treatment, all capillary
      parameters (length, volume, and surface densities) were similar to the controls
      despite a 30% enlargement of the LV. We estimate that total LV capillary length
      increased by 14% during the first 5 days and by 9% during the next 5 days of
      treatment. CONCLUSIONS: These findings indicate that capillary angiogenesis
      precedes the development of ventricular enlargement due to thyroxine
      administration. Therefore, angiogenesis in this model is not stimulated by the
      presence of hypertrophy.

PMID- 9605221
TI  - Parapagus conjoined twin Holstein calf.
AB  - BACKGROUND: Conjoined twins with a doubling of all cranial structures, having two
      vertebral columns along their entire body length yet with a single pelvis, have
      not been described in the literature. The cause of conjoined twinning is
      incompletely understood; however, two main theories (fission and fusion) have
      been proposed and disputed. METHODS: A dicephalus, tetrabrachius (parapagus)
      conjoined twin Holstein heifer calf was studied. RESULTS: Two normal heads were
      present on two necks. The twins were fused in the thoracic region. There were
      four forelimbs and an abnormal orientation of ribs. Two separate vertebral
      columns along the length of the animal ended with two tails. There was a single
      pelvis, and only two hindlimbs were present. The musculature of the medial
      forelimbs was complete but abnormally positioned. Some medial structures, caudal
      to the thorax, failed to develop in these twins. There were two hearts, each one
      supplying one half of the body. The cranial vasculature was doubled and normal.
      Caudally there were two aortas, each supplying the respective half of the twin.
      The right caudal vena cava drained all caudal parts of the body while the left
      caudal vena cava drained only the liver. There were two sets of lungs. Each twin
      had a separate esophagus that entered a separate stomach. The right abomasum
      (fourth stomach chamber) was herniated through the diaphragm into the thoracic
      cavity. The two duodenums from each stomach fused distal to the pyloric
      sphincters. Caudal to this point of fusion, all structures of the digestive and
      urogenital systems were single. The calf had a single anus and vulva.
      CONCLUSIONS: The anatomical findings in this twin suggest a fission event
      followed by fusion of parallel embryonic axes.

PMID- 9605222
TI  - Glomerular number and size: facts and artefacts.
AB  - This review article is concerned with clinical and experimental data on
      glomerular number and size and includes a critical discussion of the relevant
      stereological methods. There is considerable evidence supporting the view that
      the size of the glomerular filter, in toto, is related to the inception and
      development of glomerular disease. Major divergences from the filter size are
      incompatible with normal structure and function. Furthermore, the hypothesis has
      been put forward that there exists a subset of individuals with minor divergences
      from the norm that is more susceptible to glomerular disease than the general
      population. Stereological methods for estimating glomerular number and mean
      glomerular size could be applied to set standard values. In addition, if the
      above hypothesis is confirmed, then they could identify on biopsy specimens the
      patients that belong to cohorts at risk of developing glomerular disease.
      Unfortunately, despite the development of new, robust methods for particle
      counting and size determination, such as the fractionator and the dissector, no
      universal standards of glomerular number and size have been agreed on to date.
      The major difficulties depend on 1) establishing a standard protocol of tissue
      acquisition and processing and 2) defining possible variations across age, sex,
      and ethnic subgroups. The considerable effort required to overcome these
      difficulties should be rewarded, however, by important advances in the
      understanding of the morphogenesis of glomerular disease and in the diagnostic
      and prognostic yield of renal biopsy.

PMID- 9605223
TI  - Intercellular material in the basal and lateral folds of parotid serous cells in
      four species of bats.
AB  - BACKGROUND: Basal folds are slender plications at the basal surface of acinar
      cells in the salivary glands of many mammalian species. These largely organelle
      free folds increase the surface area of the basal plasmalemma manyfold and are
      unquestionably involved in the translocation of organic and inorganic molecules
      and water into the acinar cells. METHODS: Specimens of salivary glands were
      obtained from over 230 species of live-trapped bats from major areas of the
      globe. Tissues for electron microscopy were fixed and processed by conventional
      means. RESULTS: A number of the bat species examined had dense material in the
      intercellular spaces between basal and lateral folds of serous cells in the
      parotid gland. This intercellular material was particularly prominent in three
      species of New World bats, viz., Pteronotus parnellii, P quadridens, and
      Phyllostomus latifolius, and in one species of Old World bats, Chalinolobus
      argentatus. This dense material, which has a farinaceous texture, appears not to
      pass through tight junctions, so it is excluded from the lumina of intercellular
      canaliculi and acini. The dense material originates in the acinar cells--it is
      carried to the membranes of the folds via coated vesicles, which empty their
      dense content by exocytosis into the intercellular space. Similar dense material
      is present in the intercellular spaces of the basal labyrinth of striated ducts
      in the two species of Pteronotus. The manner in which this material accumulates
      in the striated duct is unclear. CONCLUSIONS: Although the function of the
      intracellular dense material is undetermined, it appears to be placed
      strategically to influence molecular traffic into acinar cells or to modulate the
      paracellular pathway. From a comparative evolutionary perspective, we hypothesize
      that, in bats, the combination of basal folds and extracellular densities is
      associated with insectivory. Similar morphologies appear to be lacking in
      frugivorous or nectarivorous species.

PMID- 9605224
TI  - Effect of orthodontic appliance reactivation during the period of peak expansion
      in the osteoclast population.
AB  - BACKGROUND: Delays in the appearance ofosteoclasts at compression sites occur
      following orthodontic appliance reactivation when this is done during the period
      of osteoclast recruitment. This study examined changes in alveolar bone after
      appliance reactivation at a time coinciding with the peak expansion of the
      osteoclast population following the first appliance activation. METHODS:
      Orthodontic appliances were activated with 40 g on maxillary molars followed by a
      reactivation with the same force after 4 days in one group and sham reactivation
      in the other. Rats were killed at 0, 1, 3, 6, and 10 days thereafter. Orthodontic
      movement was measured cephalometrically. TRAP and interleukin-1 alpha (IL-1alpha)
      were measured biochemically, and changes in osteoclasts and root resorption were
      assessed at both compression and tension sites histomorphometrically. RESULTS:
      Teeth in the reactivated group displayed more initial displacement than controls
      but no more tooth movement 10 days following appliance reactivation. Also,
      increases in osteoclast numbers and surface percent, as well as alveolar bone
      Tartrate-resistant acid phosphatase (TRAP), became evident in the treated animals
      only 10 days after reactivation. However, IL-1alpha was elevated in alveolar bone
      within 1 hr following appliance reactivation but returned to baseline by day 1.
      There were no treatment-related difference in nuclear number per osteoclast or
      trabecular surface per osteoclast. Significant treatment-related increases in
      root resorption were evident at compression sites by day 10. CONCLUSIONS: These
      findings indicate that after appliance reactivation during the height of
      osteoclastic stimulation, a second cohort of osteoclasts can be recruited, but
      only after a delay of several days. This delay is not due to a failure to produce
      IL-1alpha in the tissues.

PMID- 9605225
TI  - Morphological characteristics and distribution pattern of the arterial vessels in
      human cerebral cortex: a scanning electron microscope study.
AB  - BACKGROUND: The human cerebral cortex is supplied by vessels that arise from the
      pial arteries. These vessels give rise to a dense vascular network that is highly
      interconnected. Cortical arteries have been classified in different categories.
      Both their angioarchitectonic pattern and anatomical structures involved in their
      regulation are not fully understood. METHODS: Twelve fresh human brains were
      studied by scanning electron microscopy of vascular corrosion casts. RESULTS:
      Four types of arterial vessels in the cerebral cortex--short, middle, long, and
      transcortical--were identified. The cortical vascular network was formed by
      several interconnected clusters of vessels, which were arranged in four vascular
      layers parallel to the pial surface and characterized by different vascular
      densities. The greatest vascular density corresponded to the middle and deep
      vascular layers. Circular constrictions were found at the origin of cortical
      arteries and at their branching sites, probably related to vascular sphincters.
      Connections between cortical arteries were observed at their initial course.
      Plastic strips, occasionally related to constrictions, were observed around both
      middle and long cortical arteries. Other plastic structures, morphologically
      similar to pericytes, were found around capillary vessels. CONCLUSIONS: The blood
      supply to the human cerebral cortex depends on the short, middle, and long
      cortical arteries, which give rise to a highly anastomosed capillary network.
      There exist vascular connections between pial arteries and occasionally between
      cortical arteries. Blood flow autoregulation is probably mediated by smooth
      muscle cells at the arteriolar level and by pericytes at the capillary level,
      through endothelial connections.

PMID- 9605227
TI  - Ultrastructure of the binary parotid glands in the free-tailed bat, Tadarida
      thersites. I. Principal parotid gland.
AB  - BACKGROUND: Many species of bats have two sets of submandibular glands, principal
      and accessory. The accessory gland may resemble the principal one but more often
      shows wide morphological divergence. The free-tailed bat, Tadarida thersites, is
      very unusual in that it has two sets of parotid glands rather than binary
      submandibular glands. We studied the ultrastructure of the principal parotid
      gland to establish a baseline for comparison with the accessory parotid. METHODS:
      Two specimens of adult free-tailed bats, one male and one female, were live
      trapped in western Kenya. Parotid glands were fixed for electron microscopy using
      a protocol expressly designed for field fixation and then embedded by
      conventional means. RESULTS: Histologically, the principal parotid is a typical
      serous gland. The secretory granules of the endpiece cells have an unusual
      substructure in that they contain variable numbers of lucent halos and one or
      several spherules. Intercalated duct cells contain a significant number of dense,
      serous-like granules. Striated ducts have the usual basal configuration of
      mitochondria and folded plasma membranes, but the supranuclear cytoplasm contains
      many small, dense granules, so that these ducts resemble the granular convoluted
      tubules found in the submandibular glands of many families of rodents. The apices
      of the duct cells have a peculiar contour--the luminal surfaces obliquely
      invaginate into the apical cytoplasm, so that in thin section the luminal
      membranes appear to be underlaid by a layer of vacuoles. CONCLUSION: Although the
      principal parotid gland of the free-tailed bat shows some distinctive, species
      specific ultrastructural features, it basically is similar to the parotid gland
      in two other molossid bats, Tadarida brasiliensis and Molossus molossus. The
      distinctive features in the principal parotid gland of T. thersites might relate
      to its feeding on hard-bodied insects and perhaps to the production of lysozyme.

PMID- 9605226
TI  - Cytologic evidence for mechanisms of K+ transport and genesis of Hensen bodies
      and subsurface cisternae in outer hair cells.
AB  - A system commonly termed the tubulocisternal endoplasmic reticulum (TCER), but
      designated here the canalicular reticulum (CR), occurs selectively in ion
      transporting epithelia, in which it is interpreted as facilitating the
      transcellular diffusion of ions. Mechanoelectrical transduction in the cochlear
      outer hair cells (OHCs) depends on the apical influx and the subsequent
      basolateral efflux of K+. Cytologic structures that possibly mediate K+ transport
      in gerbil OHCs were investigated here. METHODS: Cochleas were fixed primarily
      with glutaraldehyde and secondarily with reagents for demonstrating TCER or were
      fixed with a ferrocyanide-osmium tetroxide solution to preserve intracellular
      membranes. The distribution of membranous structures retained with these
      techniques was examined by using electron microscopy. RESULTS: Secondary fixation
      with osmium tetroxide-ferrocyanide permitted ultrastructural demonstration in
      OHCs of increased numbers of Hensen bodies and newly detected membranous systems,
      including CR, linear cisternae, small clusters of cytosolic vesicles and
      complexes of canaliculi, segmented cisternae, and mitochondria. CR filling an
      apical stratum beside and below the cuticular plate and contacting laterally the
      uppermost subsurface cisternae (SSC) was situated to sequester and transport the
      apical K+ influx that attends the acoustically generated receptor potential and
      the silent current. The close association of CR with numerous, highly developed
      Golgi bodies exclusively in the apex of the cell suggested genesis of CR from
      Golgi cisternae. Nonbranching, linear cisternae occupied a lower cell stratum and
      spread from CR laterally to a more inferior region of the SSC. Small clusters of
      vesicles in the central cytosol resembled Hensen bodies in their envelopment by
      branching canaliculi and segmented cisternae in close association with
      mitochondria. Viewing the vesicles in Hensen bodies and the small clusters as
      functioning like most other cytoplasmic vesicles in transport of cell membrane
      permitted the interpretation that these vesicles move nascent membrane from the
      canalicular-mitochondrial complex to the SSC. Other small clusters of vesicles
      contacted the innermost layer of the SSC, often at cisterna-depleted foci in
      which the vesicles appeared to either replenish the SSC or arise in the course of
      its turnover. Proximity of multivesicular bodies and lysosomes to small vesicle
      clusters in foci of depleted SSC implicated the lysosomes in digesting vesicles
      released from the SCC. Populations of unique, large, lysosome-like bodies and of
      small, dense bodies in the upper cytosol of OHCs appeared to be involved in
      different catabolic pathways mediating the turnover ofSSC, CR, and other
      structures. CONCLUSIONS: Cochlear OHCs contain previously unrecognized membranous
      organelles that facilitate ion transport and presumably contribute thereby to
      mechanoelectrical transduction. Vesicles in small clusters and Hensen bodies
      arise from complexes of canaliculi, cisternae, and mitochondria and contribute
      membrane to the genesis of the SSC.

PMID- 9605228
TI  - Ultrastructure of the binary parotid glands in the free-tailed bat, Tadarida
      thersites. II. Accessory parotid gland.
AB  - BACKGROUND: Many bat species have an extra set of major salivary glands. In some
      species, the accessory glands are quite similar to the principal one, but in
      others they may be radically different. Accessory glands usually are associated
      with the submandibular gland, but the free-tailed bat, Tadarida thersites, also
      has an accessory parotid gland. In the present study, we compared the accessory
      parotid gland with its principal counterpart. METHODS: Salivary glands were
      removed from two specimens of free-tailed bats, one of each sex, that had been
      live-trapped in western Kenya and immersion-fixed in a specially formulated
      mixture designed for field fixation. Once back in the laboratory, the tissue was
      further prepared for electron microscopy by conventional means. RESULTS: The
      secretory endpieces consist of serous tubules composed of typical serous cells
      that contain numerous dense granules. In contrast, the intralobular duct system
      shows a radical departure from normal. These ducts are enormous in caliber, their
      lumina measuring greater than 100 microm in diameter. They appear to arise by
      amalgamation of the homologues of intercalated and striated ducts into
      macroducts. The walls of the macroducts consist of intermingled patches of simple
      cuboidal and simple columnar epithelia that occasionally include a tuft cell and
      are underlaid by an almost continuous layer of myoepithelium. A few cells have
      some modified basal striations, but most cells display a cytological organization
      that differs radically from either of their two putative ancestral cell types.
      Both tall and short epithelial macroduct cells have a paranuclear collection of
      ovate mitochondria and aggregates of what presumably are peroxisomes. Macroduct
      cells in both the female and male are pervaded by a system of tubular smooth
      endoplasmic reticulum (SER). In the female, the SER gives rise to membranous
      whorls that consist of numerous plies. As the macroducts approach their termini,
      a single row of small dense secretory granules appears just beneath their luminal
      surface. At the lobular periphery, the ducts taper down to become excretory ducts
      of normal dimensions. CONCLUSIONS: An accessory parotid gland occurs in T.
      thersites, but apparently is absent in the related species, T. brasiliensis. The
      ultrastructural data are consistent with a possible steroidogenic function,
      although other features of the gland might relate to the elaboration of a
      secretory product associated with feeding on chitinous beetles. The macroducts
      conceivably function as reservoirs of preformed saliva.

PMID- 9605229
TI  - Transendoscopic chemical ablation of progressive ethmoidal hematomas in standing
      horses.
AB  - OBJECTIVE: To examine the response of horses with progressive ethmoidal hematoma
      (PEH) to intralesional injection of 4% formaldehyde solution. STUDY DESIGN: Nasal
      passages of horses affected with PEH were examined endoscopically at different
      intervals to determine the effects of intralesional injection of formaldehyde
      solution. ANIMALS: 21 horses with PEH. METHODS: PEHs were injected
      transendoscopically with 4% formaldehyde solution. Horses were examined
      endoscopically and retreated at different intervals until the PEH was eliminated
      or was so small that reinjection was not possible. RESULTS: Lesions diminished
      significantly in size or were eliminated after 1 to 18 injections (median, 5;
      mean, 7.0 +/- 5.62). Seventeen lesions (60.7%) resolved completely after 1 to 18
      injections (median, 5; mean, 7.2 +/- 5.71). Five lesions decreased markedly in
      size but did not resolve after receiving 1 to 18 injections (median, 5; mean, 7.6
      +/- 6.66). Injection of these lesions was discontinued 4.0 to 25.1 months
      (median, 9.5; mean, 11.02 +/- 8.446) after the first injection. The PEH of one
      horse was removed surgically after one injection. Three horses, one with
      bilateral PEH, were lost to follow-up. One horse developed signs of laminitis. No
      other complications were observed. CONCLUSIONS: Horses with a PEH can be treated
      effectively by transendoscopic, intralesional injection of 4% formaldehyde
      solution. CLINICAL RELEVANCE: Ablation of PEH using formaldehyde solution avoids
      general anesthesia and problems associated with ablation by conventional surgery
      or laser.

PMID- 9605231
TI  - The effect of triple pelvic osteotomy on the articular contact area of the hip
      joint in dysplastic dogs: an in vitro experimental study.
AB  - OBJECTIVE: To investigate the effect of triple pelvic osteotomy (TPO) on
      articular contact area and acetabular coverage of dysplastic hip joints in dogs.
      STUDY DESIGN: Articular contact area and femoral head coverage by the acetabulum
      were computed in vitro in normal and dysplastic canine hips. The effect of TPO on
      articular contact and coverage was then analyzed in the dysplastic hips. Sample
      Population-Five normal and six dysplastic canine cadaver specimens. METHODS:
      Contact area and coverage of loaded hips were computed using serial computed
      tomography scan images before and after TPO. Three angles of acetabular
      ventroversion (AVV) were studied (20 degrees, 30 degrees, and 40 degrees). Using
      a custom-designed hinge plate, angles of spontaneous hip reduction in dysplastic
      hips were compared with previously recorded angles of reduction determined by the
      Ortolani test. RESULTS: Contact area significantly increased from 0 degrees to 30
      degrees of AVV, then remained virtually unchanged. Coverage significantly
      increased from 0 degrees to 20 degrees of AVV. Both contact and coverage of
      normal hips were similar, yet significantly smaller than those of dysplastic hips
      once reduction had occurred. The experimental angles of reduction were
      significantly smaller and poorly correlated with the angles of reduction
      determined by the Ortolani test. Although coverage continued to increase with
      AVV, the actual joint contact area did not significantly vary after relocation of
      the femoral head. CONCLUSIONS: This study suggests that increasing AVV beyond 20
      degrees does not significantly improve the beneficial effects of TPO and
      therefore should be carefully weighed against increased risks of postoperative
      complications associated with large angles of AVV.

PMID- 9605230
TI  - Circumferential suture of the mitral annulus for correction of mitral
      regurgitation in dogs.
AB  - OBJECTIVE: To develop a method for reducing mitral regurgitation in dogs by
      positioning and tightening a circumferential suture around the mitral valve
      annulus. STUDY DESIGN: Description of clinical cases. ANIMALS: 15 dogs with
      spontaneous mitral valve disease, annular dilation, and refractory congestive
      heart failure treated between 1962 and 1994. METHODS: A composite suture material
      was constructed using braided Teflon-impregnated polyester sternotomy suture,
      barium sulfate thread, and Silastic tubing. Through a left lateral thoracotomy,
      the suture was positioned around the mitral annulus by passing it through the
      coronary sinus, right atrium, and underneath the left coronary arteries before
      tightening it. RESULTS: Six dogs died during surgery because of hemorrhage from
      the left atrium, coronary sinus, or left coronary artery. Three dogs died
      postoperatively because of coronary artery compression by the suture.
      Satisfactory suture placement was achieved in six dogs, three of which were long
      term survivors (6 to 26 months) before they were euthanatized for noncardiac
      reasons. CONCLUSIONS: Reduction of mitral annulus diameter with a circumferential
      purse-string suture does not require cardiopulmonary bypass. The surgery is
      technically difficult, and detailed knowledge of coronary artery anatomy is
      required. The current suture design is inexpensive, radiopaque, and
      biocompatible; no special instruments are required for placement. CLINICAL
      RELEVANCE: Mitral regurgitation is the most common cardiovascular disorder in
      dogs and the most common cause of congestive heart failure. Annular dilation
      occurs as a consequence of mitral regurgitation. Placement and tightening of a
      circumferential suture around the mitral annulus reduces the degree of mitral
      regurgitation.

PMID- 9605232
TI  - Congenital interruption of the portal vein and caudal vena cava in dogs: six case
      reports and a review of the literature.
AB  - OBJECTIVE: To describe six dogs with congenital abnormalities involving the
      portal vein, caudal vena cava, or both. ANIMALS: Six client-owned dogs with
      congenital interruption of the portal vein or the caudal vena cava, or both.
      METHODS: Portal vein and caudal vena cava anatomy was evaluated by contrast
      radiography and visualization at surgery. Vascular casts or plastinated specimens
      were obtained in three animals. RESULTS: Portal blood shunted into the caudal
      vena cava in four dogs and the left hepatic vein in one. Two of these five dogs
      also had interruption of the caudal vena cava with continuation as azygous vein,
      as did an additional dog, in which the portal vein was normally formed. Portal
      vein interruption was present in 5 of 74 (6.8%) dogs with congenital
      portosystemic shunts evaluated at the Veterinary Teaching Hospital during the
      study period. CONCLUSIONS: Serious malformations of the abdominal veins were
      present in more than 1 in 20 dogs with single congenital portosystemic shunts.
      CLINICAL RELEVANCE: Veterinarians involved in diagnosis and surgery for
      portosystemic shunts should be aware of these potential malformations, and portal
      vein continuity should be evaluated in all dogs before attempting shunt
      attenuation.

PMID- 9605233
TI  - Short-term hemodynamic evaluation of circumferential mitral annuloplasty for
      correction of mitral valve regurgitation in dogs.
AB  - OBJECTIVE: To determine the short-term hemodynamic effects associated with
      circumferential mitral annuloplasty (CMA) in dogs with mitral regurgitation.
      STUDY DESIGN: Prospective experimental study. Animals-Seven healthy adult mongrel
      dogs. METHODS: Mitral regurgitation was surgically induced, and annular dilation
      occurred. Echocardiography and cardiac catheterization were used to determine
      forward ejection fraction (FEF), regurgitant fraction (RF), pulmonary capillary
      wedge pressure (PCWP), and annular diameter before and immediately after CMA in
      five dogs. FEF and RF were also evaluated 7 days after annuloplasty. RESULTS:
      Mean annular diameter and PCWP were significantly reduced immediately after CMA.
      Significant increases in FEF of 19% and 22% were shown immediately and 7 days
      after CMA. Significant reductions in RF of 19% and 22% were also shown
      immediately and 7 days after annuloplasty. CONCLUSIONS: Sustained hemodynamic
      benefits and a reduction in annular diameter were achieved by CMA in a canine
      model of mitral regurgitation. CLINICAL IMPLICATIONS: CMA may be a suitable
      treatment for heart failure because of mitral regurgitation when early signs of
      cardiovascular decompensation persist despite appropriate medical management.

PMID- 9605234
TI  - Mechanical comparison of two external fixator clamp designs.
AB  - OBJECTIVE: To compare two external fixation clamp designs for their ability to
      resist movement of a fixation pin in relation to the connecting rod. STUDY
      DESIGN: Two designs of external fixator clamps were attached to connecting rods
      mounted on a jig for mechanical testing. Fixator pins were placed perpendicular
      to the connecting rod. A mechanical testing machine was used to deflect each 3.2
      mm pin at a distance that was 25 mm from the center of the clamp bolt. Both clamp
      designs were tightened to 4.4, 6.1, and 7.8 newton-meters (N x m) torque, and
      loads were applied in a position ramp through 4 mm and resisting loads were
      measured. Two clamp orientations were used during load application, such that the
      deflection of the pin tended to tighten the clamp bolt or tended to loosen the
      clamp bolt. The tests were videotaped to determine mode of failure. Comparisons
      of the load/displacement curves for the two external fixator clamp designs were
      made using nonlinear equational curve fitting methods. The resultant plateau and
      rise coefficients were compared using analysis of variance. RESULTS: Slippage of
      the pin in relation to the clamp occurred with the Kirschner-Ehmer clamp
      tightened to 4.4, 6.1, and 7.8 N x m, and slipping of the pin in relation to the
      clamp occurred with the experimental clamp design tightened to 4.4 and 6.1 N x m
      but not to 7.8 N m. At 7.8 N x m, the 3.2-mm pin deformed plastically with the
      experimental clamp design. Increasing the torque of the clamp bolt resulted in
      superior plateau coefficients for both clamp designs. At each level of tightness
      and in each clamp orientation to applied pin load, the experimental clamp design
      provided greater plateau coefficients than did the Kirschner-Ehmer clamp design.
      At 7.8 N x m of tightness, the Kirschner-Ehmer clamp and bolt bent, whereas only
      slight plastic deformation of the experimental clamp design occurred.
      CONCLUSIONS: The experimental external fixator clamp was more secure in resisting
      fixator pin movement at all levels of tightening compared with the Kirschner
      Ehmer-type external fixator clamp. At 7.8 N x m of tightening, the new clamp
      design did not allow slippage of the pin within the clamp. CLINICAL SIGNIFICANCE:
      The experimental external fixator clamp should result in greater rigidity of
      fixator configurations, in addition to providing design features that allow
      addition of a clamp between two installed clamps, sleeved predrilling of pilot
      holes for all pins, measurement of pin depth, and placement of positive profile
      pins at all sites.

PMID- 9605235
TI  - Hinged Ilizarov external fixation for correction of antebrachial deformities.
AB  - OBJECTIVE: To evaluate hinged circular external fixation for correction of
      antebrachial deformities in dogs. STUDY DESIGN: Uncontrolled clinical trial.
      ANIMAL POPULATION: Seven client-owned dogs. METHODS: Six dogs had one radius
      corrected and one dog had both radii corrected. Preoperative planning included
      measurement of the craniocaudal and mediolateral angular deformities, rotational
      deformity, length deficit, origin of deformity, graphical or mathematical
      determination of the amplitude and direction of the actual limb deformity, and
      frame assembly. RESULTS: Preoperatively, function and cosmesis were assessed to
      be fair to poor in all dogs. Deformity correction started 48 to 60 hours
      postoperatively and ranged from 0.46 mm to 1.36 mm twice daily. Hospitalization
      time ranged from 4 to 6 days. Corrections were mostly made by the owners, at
      home. Lengthening and angular correction ranged from 3 to 38 mm and 18 degrees to
      48 degrees. Mean residual deformities were 2.7% of radial length and 2.7 degrees.
      The time duration with the circular external fixators in place ranged from 29 to
      71 days. Two additional surgeries were necessary in one dog because of wire
      breakage. Mean follow-up was 40 months. Long-term function and cosmesis were good
      to excellent in all dogs. CONCLUSION: Although complications were present in six
      of seven dogs, the outcome of hinged Ilizarov external fixation was successful in
      all dogs treated for deformities of the antebrachium. CLINICAL RELEVANCE: Despite
      complex preoperative planning, the placement of hinged circular external fixators
      is straightforward, and allows precise correction of complex antebrachial
      deformities with minimal tissue trauma.

PMID- 9605236
TI  - Results of transsphenoidal hypophysectomy in 52 dogs with pituitary-dependent
      hyperadrenocorticism.
AB  - OBJECTIVE: To evaluate microsurgical transsphenoidal hypophysectomy in dogs with
      pituitary-dependent hyperadrenocorticism (PDH). STUDY DESIGN: Prospective study
      to evaluate the results (survival and disease-free interval, remission,
      recurrence) and complications of microsurgical transsphenoidal hypophysectomy by
      clinical follow-up, computed tomography (CT), and urinary corticoid-to-creatinine
      (C/C) ratios in dogs with PDH. The effect of surgical experience was investigated
      by comparing results of hypophysectomy cases 1 through 26 and 27 through 52.
      ANIMALS OR SAMPLE POPULATION: 52 dogs with PDH. RESULTS: Preoperative CT enabled
      accurate assessment of pituitary size (24 nonenlarged and 28 enlarged) and
      localization relative to intraoperative anatomic landmarks. Treatment failures
      included procedure-related mortalities (five dogs) and incomplete
      hypophysectomies (four dogs). The 1-year estimated survival rate was 84% (95%
      confidence interval [CI], 71% to 92%). The 2-year estimated survival rate was 80%
      (95% CI, 65% to 90%). In 43 dogs, the hyperadrenocorticism went into remission.
      Hyperadrenocorticism recurred in five dogs. The 1-year estimated relapse-free
      fraction was 92% (95% CI, 76% to 97%). The main complications were transient,
      mild, postoperative hypernatremia; transient reduction or cessation of tear
      production (25 eyes in 18 dogs); permanent (five dogs) or prolonged (nine dogs)
      diabetes insipidus; and secondary hypothyroidism. Normal tear production had
      resumed in all but one case after a median period of 10 weeks. In the second case
      series (27 through 52), the hospitalization period was shorter, the number of dry
      eyes fewer, the survival fraction greater, and the postoperative mortality lower
      than in the first series. In 15 dogs in which remission was obtained,
      postoperative CT images suggested the presence of small pituitary remnants; in 1
      of these, hyperadrenocorticism recurred. In 46 dogs, the histological diagnosis
      was pituitary adenoma. CONCLUSIONS: Microsurgical transsphenoidal hypophysectomy
      in dogs with PDH is an effective method of treatment in specialized veterinary
      institutions having access to advanced pituitary imaging techniques.
      Postoperative CT findings do not correlate well with remission or subsequent
      recurrence of hyperadrenocorticism. CLINICAL RELEVANCE: The neurosurgeon
      performing hypophysectomies must master a learning curve and must be familiar
      with the most frequent complications of the operation to recognize them as early
      as possible and to treat them immediately and effectively. Urinary C/C ratios are
      sensitive indicators for the assessment of remission and recurrence of
      hyperadrenocorticism.

PMID- 9605238
TI  - Single-stage revision using an uncemented, porous-coated, anatomic endoprosthesis
      in two dogs: case report.
AB  - OBJECTIVE: To describe the clinical and radiographic features of septic and
      aseptic failure of two femoral endoprostheses and their successful revision.
      STUDY DESIGN: Case report. ANIMALS OR SAMPLE POPULATION: Two skeletally mature
      male research dogs. METHODS: An uncemented porous-coated anatomic (PCA)
      endoprosthesis was implanted in a single-stage revision procedure after thorough
      debridement and lavage of the femoral canal. An autogenous cancellous bone graft
      was used in dog 2 (aseptic loosening). Serial clinical and radiographic
      examinations were performed postoperatively. The dogs were euthanatized 1 year
      (dog 1) and 2 years (dog 2) after revision surgery, and necropsy was performed.
      High-resolution contact radiographs and histopathologic evaluation of femoral
      sections were obtained. RESULTS: The cause of implant failure was septic
      loosening in dog 1 and aseptic loosening in dog 2. In both dogs, clinical
      function returned to normal after revision. Serial radiographic assessment after
      revision documented disappearance of the bone pedestal and the periprosthetic
      lucency. Cancellous hypertrophy seen adjacent to the proximal porous-coated
      region of the implants provided radiographic evidence of bony fixation.
      Histological evaluation of femoral sections documented successful implant
      integration with bone and fibrous tissue. CONCLUSION: Revision with an uncemented
      implant in a single-stage procedure was successful in the two dogs described in
      this report. CLINICAL RELEVANCE: This report provides a detailed description of
      the clinical course and serial radiographic assessment of septic and aseptic
      loosening of two femoral endoprostheses. Single-stage revision is a potential
      treatment for either condition as demonstrated by the successful outcome in these
      two dogs.

PMID- 9605237
TI  - Surgical management of multiple congenital intrahepatic shunts in two dogs: case
      report.
AB  - OBJECTIVE: To present details of an unusual type of portosystemic shunt and its
      surgical management in two dogs. ANIMALS: Two young dogs that had a tentative
      diagnosis of a portosystemic shunt on the basis of clinical signs and serum
      biochemical abnormalities. Abdominal ultrasonography and contrast portography
      demonstrated multiple intrahepatic shunts. In both cases, the multiple shunts
      arose from a single branch of the portal vein. OUTCOME: It was possible to locate
      and attenuate flow through the shunts via a transportal venotomy under conditions
      of hepatic vascular occlusion. Clinical and biochemical abnormalities resolved
      after surgery in both dogs. Postoperative sonography revealed complete
      obliteration of the shunt plexus in one of the dogs.

PMID- 9605239
TI  - Neuromuscular effects of doxacurium chloride in isoflurane-anesthetized dogs.
AB  - OBJECTIVE: To determine the neuromuscular effects of doxacurium chloride and to
      construct a dose-response curve for the drug in isoflurane-anesthetized dogs.
      DESIGN: Randomized, controlled trial. ANIMALS: Six healthy, adult, mixed-breed
      dogs (five female, one male) weighing 24.8 +/- 2.8 kg. METHODS: Anesthesia was
      induced with isoflurane in oxygen and maintained with 1.9% to 2.3% end-tidal
      isoflurane concentration. PaCO2 was maintained between 35 and 45 mm Hg with
      mechanical ventilation. Mechanomyography was used to quantitate the evoked twitch
      response of the paw after supramaximal train-of-four stimulation of the
      superficial peroneal nerve. After baseline values were recorded, the dogs
      received one of three doses of doxacurium (2.0, 3.5, 4.5 microg/kg of body
      weight) or a saline placebo intravenously in random order. All dogs received all
      treatments with at least 7 days between studies. After drug administration, the
      degree of maximal first twitch depression compared with baseline (T1%) was
      recorded. Dose-response relations of doxacurium were plotted in log dose-probit
      format and analyzed by linear regression to determine effective dose (ED50 and
      ED90) values for doxacurium. RESULTS: The median log dose-probit response curve
      showed good data correlation (r = .999) with estimates of the ED50 (2.1
      microg/kg) and ED90 (3.5 microg/kg) for doxacurium in isoflurane-anesthetized
      dogs. Mean +/- SD values for T1% (first twitch tension compared with baseline) at
      maximal depression after drug administration, onset (time from drug
      administration to maximal depression of T1%), duration (time from maximal
      depression of T1% to 25% recovery of T1%), and recovery (time from 25% to 75%
      recovery of T1%) times were 92% +/- 4%, 40 +/- 5 minutes, 108 +/- 31 minutes, and
      42 +/- 11 minutes for dogs treated with 3.5 microg/kg of doxacurium and 94% +/-
      7%, 41 +/- 8 minutes, 111 +/- 33 minutes, and 37 +/- 10 minutes for dogs treated
      with 4.5 microg/kg of doxacurium. CONCLUSION AND CLINICAL RELEVANCE: We conclude
      that doxacurium is a long-acting neuromuscular blocking agent with a slow onset
      of action. Doxacurium can be used to provide muscle relaxation for long surgical
      procedures in isoflurane-anesthetized dogs. Interpatient variability,
      particularly of duration of drug action, may exist in the neuromuscular response
      to the administration of doxacurium in dogs.

PMID- 9605241
TI  - The effect of cocaine on mitogen-induced lymphyocyte proliferation in pregnant
      women.
AB  - Cocaine use during pregnancy is associated with increased risk of sexually
      transmitted diseases, including syphilis and HIV. Many sociological and economic
      factors related to cocaine use have been shown to contribute to this increased
      risk. Cocaine may also affect immunological function thereby increasing risk for
      sexually transmitted diseases. The objective of this study was to determine if
      cocaine suppresses mitogen-induced lymphocyte proliferation in pregnant women.
      Peripheral blood mononuclear cells were obtained from 39 pregnant women.
      Lymphocyte proliferation was stimulated with concanavalin A (conA, 1 microg/mL).
      Cocaine was added at time zero to one set of cultures and at 0, 24, and 48 hr to
      a second set of cultures (to correct for cocaine degradation in culture). Three
      doses of cocaine were used: 0.1, 1 and 10 microg/mL. The cells were pulsed with 1
      microCi 3H thymidine at 72 hr and harvested 19 hr after addition of the isotope.
      Lymphocyte proliferation, as determined by radioactivity (cpm) was assessed.
      Cocaine had no statistically significant effect on conA-stimulated lymphocyte
      proliferation when added at time = 0 or when added daily. Cocaine, in
      concentrations similar to those found in clinical experiments with drug users,
      does not suppress in vitro concanavalin A-induced lymphocyte proliferation in
      cells obtained from pregnant women.

PMID- 9605240
TI  - The effects of equivalent doses of tromethamine or sodium bicarbonate in healthy
      horses.
AB  - OBJECTIVE: To describe the effects of tromethamine, a putative treatment for
      metabolic acidosis, and to compare its biochemical effects with those of sodium
      bicarbonate. DESIGN: Randomized intervention study with repeated measures.
      ANIMALS: 16 healthy horses, 3 to 17 years old, weighing 391 to 684 kg. METHODS:
      Ten horses received 3 mEq/kg tromethamine and six received 3 mEq/kg sodium
      bicarbonate. Samples of venous blood and cerebrospinal fluid (CSF) were collected
      at intervals before and after drug administration. Heart rate and breathing rate
      were also recorded at intervals. RESULTS: Median standard base excess increased
      significantly (P < .05) from baseline immediately after both bicarbonate and
      tromethamine. These increases were not significantly different between
      treatments. Standard base excess returned toward baseline but remained
      significantly increased 3 hours after infusion of either treatment. After
      tromethamine, there was a significant decrease in plasma sodium concentration
      that lasted for at least 90 minutes. After sodium bicarbonate, no change in
      plasma sodium concentration was detected. Both sodium bicarbonate and
      tromethamine increased carbon dioxide tension in venous blood and CSF. Despite
      venous alkalemia, the pH of CSF decreased after both treatments. CONCLUSIONS:
      Tromethamine and sodium bicarbonate have similar alkalinizing ability.
      Tromethamine causes hyponatremia, whereas both tromethamine and sodium
      bicarbonate increase carbon dioxide tension in venous blood and CSF. CLINICAL
      RELEVANCE: If hyponatremia, hypercarbia, and acidosis of the CSF occur after
      tromethamine is given to horses with existing metabolic acidosis, some of the
      potential advantages of tromethamine may prove theoretical rather than practical.

PMID- 9605242
TI  - Grief support programs: patients' use of services following the loss of a desired
      pregnancy and degree of implementation in academic centers.
AB  - Limited information is available concerning what resources to offer and how to
      best counsel patients after the loss of a desired pregnancy. The Touching Hearts
      Program at the University of Iowa offers support for such patients and their
      families. We reviewed responses to a questionnaire (n=128) sent to families who
      received support from the program. Data was evaluated using descriptive
      statistics or Pearson's Chi-square. A p value of <0.05 was considered
      statistically significant. Sixty-four percent of patients reported visiting with
      the chaplain, 67% had their baby blessed or baptized, and 80% held a funeral or
      memorial service. Ninety-two percent of patients were offered private time with
      their baby, and 87% elected to do so. While 66% of patients felt they had
      adequate time with their child, 85% indicated they would have appreciated
      additional opportunities to see their baby. Resources offered by the Touching
      Hearts Program were highly utilized by patients. Changes in health care may
      decrease funding for such programs, however, high patient utilization indicates a
      need for grief support programs at facilities involved in management of abnormal
      pregnancies. A survey of academic centers showed that the vast majority offer
      similar programs to their patients.

PMID- 9605243
TI  - Successful tocolysis: does cervical change affect time to delivery?
AB  - Generally, it is preferable to tocolyze patients with idiopathic preterm labor
      (PTL). Little information is available about ultimate outcomes after successful
      tocolysis. Our objective is to evaluate the relationship between cervical change
      after the initiation of tocolysis and the delay in time to delivery in patients
      with preterm labor. A historical analysis of all patients with successful
      tocolysis after PTL between January 1992 and December 1993 was undertaken. The
      patients were then placed in one of three categories (regression, unchanged, or
      progression) based on cervical change after the initiation of tocolysis. Various
      demographic pregnancy characteristics and pregnancy outcome data were analyzed.
      One hundred and twenty-six patients had successful tocolysis and met the
      admission criteria. Patients who had cervical progression had shorter delay to
      delivery, delivered at an earlier gestational age (31.7 weeks compared to 34.0
      and 34.1 weeks, respectively, p < 0.05), and were more likely to deliver before
      35 weeks (88% compared to 50.0 and 55.0%, respectively, p < 0.05). Also, neonates
      remained in the hospital longer and were more likely to have respiratory distress
      syndrome when compared to the other two groups. Patients who had cervical
      progression after the initiation of tocolysis are more likely to deliver
      prematurely, had a shorter delay to delivery, and delivered lower birth weight
      infants than did patients whose cervix regressed or remained unchanged. In our
      population, patients who had successful tocolysis had a preterm delivery rate of
      59.5% before the 35th week of gestation.

PMID- 9605244
TI  - Antepartum bilateral ovarian vein thrombosis: magnetic resonance imaging
      diagnosis.
AB  - Antepartum cases of ovarian vein thrombosis are extremely rare and often
      misdiagnosed. A 22-year-old nullipara at 29 weeks' gestation presented with right
      lower quadrant pain and fever. Sonography revealed a tubular, hypoechoic mass. At
      laparotomy, a noninflamed appendix was found and a 2 x 4 cm retroperitoneal mass
      was palpated near the right ureter. Postoperative magnetic resonance imaging
      (MRI) revealed bilateral thrombosis of the ovarian veins with caval extension.
      Therapeutic anticoagulation was achieved, but the patient underwent cesarean
      delivery 4 days later due to active labor and malpresentation. Postoperative MRI
      showed no extension of the thrombi, and her postpartum course was otherwise
      unremarkable. MRI is a valuable, noninvasive tool in the diagnosis of venous
      thrombi in pregnancy.

PMID- 9605245
TI  - Usefulness of coagulation studies and blood banking in patients with symptomatic
      placenta previa.
AB  - We conducted this study to ascertain the usefulness of coagulation studies and
      blood bank utilization in the patient with symptomatic placenta previa. During a
      2-year interval, 97 patients with uterine bleeding due to placenta previa
      diagnosed > or = 24 weeks' gestation were evaluated. The following studies were
      routinely obtained: complete blood count including platelet count, fibrinogen,
      prothrombin time, and a Kleihauer-Betke test. A type and cross-match was sent to
      the blood bank, and blood availability was maintained for all patients throughout
      the course of hospitalization. For 92 of 97 patients the laboratory values and
      need for immediate blood availability were analyzed. No abnormal prothrombin
      times or Kleihauer-Betke tests were found. There was one low fibrinogen value in
      a patient with a normal complete blood count. The initial hematocrits ranged from
      16.5 to 40.0%, and the initial hemoglobins ranged from 5.5 to 14.1 mg/dL. Five
      patients had platelet counts of < or = 150 k/mm3 (range 75 to 149 k/mm3).
      Fourteen patients (14.6%) required transfusion, two received their transfusion
      antepartum and 12 received perioperative transfusion with a cesarean delivery.
      During this time period, only two patients required emergent delivery within 1 hr
      of presentation to the hospital. One patient had delayed seeking medical
      attention for more than 3 hr prior to admission despite significant hemorrhage.
      Coagulation studies and Kleihauer-Betke tests have limited utility in the
      symptomatic patient with uterine bleeding from placenta previa. Continuous
      availability of cross-matched blood in the antepartum period appears unnecessary
      as no patients in this investigation were transfused emergently.

PMID- 9605247
TI  - The effect of nifedipine on urinary excretion of calcium in preeclampsia.
AB  - Our objective was to determine if maternal urinary calcium excretion is altered
      during treatment of mild preeclampsia remote from term with the calcium channel
      blocker nifedipine. One hundred forty-eight women with mild preeclampsia were
      randomly allocated to treatment with either bed rest alone (n=64) or in
      combination with nifedipine (n=84) at 26-36 weeks' gestation. All women had 24 hr
      urine samples collected for creatinine clearance and calcium excretion
      determination prior to therapy and during treatment. There was no difference in
      gestational age at the time of urine collection between the two groups. There
      were no differences in 24-hr creatinine clearance and calcium excretion between
      the groups prior to therapy. When followed longitudinally, there was a
      significant reduction in calcium excretion within each group (p=0.0005 control
      group, p <0.0001 nifedipine group). Further, a significant reduction in calcium
      excretion was noted following nifedipine therapy (62+/-94 mg Ca/24 hr) compared
      to the control group (143+/-153 mg Ca/24 hr), p <0.001. Consistent with previous
      studies, we have shown that progressive hypocalciuria is a feature of
      preeclampsia. Further, urinary calcium excretion decreased despite nifedipine
      therapy. Altered urinary calcium excretion may be less reflective of the
      progression in severity of preeclampsia in patients treated with nifedipine.

PMID- 9605249
TI  - Mandibular arteriovenous malformation in pregnancy.
AB  - Benign vascular lesions, such as hemangiomas of childhood, arteriovenous
      malformations (AVMs) and venous malformations, are uncommon and have been found
      in a variety of organs throughout the body. Vascular lesions of bone are found
      most often in the vertebral column. Vascular tumors of the mandible are rare. We
      report a case of a mandibular AVM found in a pregnant woman at 35 weeks'
      gestation. A pregnant woman presented at 35 weeks' gestation with right-sided jaw
      pain and was found to have a pulsatile mass on the internal surface of the right
      mandible in the area of the premolars. Profuse bleeding of the lesion required
      emergent selective arterial embolization of a vascular tumor of the mandible,
      which resulted in successful occlusion of the vessels. Uncomplicated vaginal
      delivery followed induction of labor. Excision and reconstructive surgery
      occurred 1 week postembolization. Pathology confirmed an AVM. Mandibular AVMs are
      rare vascular tumors that, when correctly diagnosed, can be successfully managed
      during pregnancy. Whether or not vascular or hormonal changes associated with
      pregnancy can exacerbate a preexisting AVM is debatable.

PMID- 9605248
TI  - Maternal serum uric acid levels in preeclamptic women with multiple gestations.
AB  - Our study was designed to determine serum uric acid levels and establish
      clinically useful cutoff values for the diagnosis of preeclampsia in twin and
      triplet gestations. We reviewed the medical records of 129 multiple gestations
      with serum uric acid levels available. Fifty-five twin gestations were
      complicated by preeclampsia, 51 were not. Fifteen triplet gestations were
      complicated by preeclampsia, and 8 were not. Preeclampsia was defined as a
      persistent blood pressure > or =140/90 mmHg, and proteinuria, or elevated liver
      enzymes, thrombocytopenia, or eclamptic seizure. Receiver operating
      characteristic curves were generated for twin and triplet gestations. Serum uric
      acid levels at different stages of gestation in twin gestations were determined.
      Maternal serum uric acid levels in preeclamptic twin and triplet gestations were
      significantly higher than those in nonpreeclamptics. Serum uric acid levels at
      varying gestational ages were significantly higher in preeclamptic twin
      gestations than in nonpreeclamptics. Maternal serum uric acid levels of 6.3 mg/dL
      and 6.8 mg/dL were found to be the most useful cutoff values for the diagnosis of
      preeclampsia in twin and triplet gestations, respectively. We conclude that
      compared to nonpreeclamptics, preeclamptic women with multiple gestations had
      significantly higher serum uric acid levels. Mean serum uric acid levels based on
      gestational age should be justified for the diagnosis of preeclampsia in multiple
      gestations.

PMID- 9605250
TI  - Plasma and erythrocyte profiles of nonesterified polyunsaturated fatty acids
      during normal pregnancy and labor.
AB  - This study was undertaken to determine the plasma and erythrocyte profiles of
      metabolically important nonesterified polyunsaturated fatty acids (PUFA), that
      is, free fatty acids, in each trimester of pregnancy and in labor. Blood was
      drawn from patients in the first, second, and third trimester and in labor.
      Nonesterified polyunsaturated fatty acids were extracted from erythrocytes with
      chloroform and methanol. The PUFAs from erythrocytes and plasma were then
      measured in their methylester form using high performance liquid chromatography
      (HPLC). Plasma levels of all PUFAs were similar in each trimester of pregnancy
      but levels of linoleic and linolenic acids were higher in laboring patients.
      Plasma levels of linoleic and arachidonic acid in the n-6 pathway (range 40 to
      162 mg/L plasma) were higher than linolenic, eicosapentaenoic, and
      docosahexaenoic acids measured in the n-3 pathway (range 2.1 to 12.8 mg/L
      plasma). PUFA levels in erythrocytes were generally higher in the second
      trimester (range 2.6 to 79.7 mg/100-microL spun erythrocytes). In these
      erythrocytes, docosahexaenoic acid in the n-3 pathway and linoleic and
      arachidonic acids in the n-6 pathways were present in the highest amounts.
      Polyunsaturated fatty acids appear to be absorbed and mobilized in increasing
      amounts in plasma and erythrocytes with advancing gestational age and labor. This
      activity appears to be most pronounced in the second trimester. Further
      investigations into PUFA metabolism and the mechanisms which govern it could lead
      to a better understanding of the role of these important substances in normal and
      abnormal pregnancies as well as in the initiation of labor.

PMID- 9605246
TI  - Circulating thrombomodulin levels and clinical correlates in pregnant diabetics.
AB  - The object of this study was to investigate the relationship of thrombomodulin
      (TM) and glycosylated hemoglobin (HbA1C) in pregnant diabetics and to determine
      clinical correlates. We performed a prospective cohort study of 53 patients: 25
      women with insulin-dependent diabetes (group 1) and 28 with gestational diabetes
      (group 2). Group 1 underwent monthly determinations of HbA1C and TM. Group 2
      underwent determination at 36 weeks of gestation. There was a significant
      difference in HbA1C between groups 1 and 2 (p=0.0005), but there was no
      difference in TM. There was no correlation between TM and HbA1C. TM levels
      correlated positively with serum creatinine (r=0.46, p=0.002), proteinuria
      (r=0.48, p=0.007), and duration of diabetes (r=0.41, p=0.042). TM was
      significantly higher in diabetics of advanced White Classification (p=0.008).
      With good control, TM does not appear to be elevated in a diabetic pregnancy. TM
      may be a marker of endothelial damage that correlates more with duration of
      diabetes and renal disease than with HbA1C, which reflects short-term control.

PMID- 9605252
TI  - Correlation of urine and serum benzoylecgonine levels in pregnant women.
AB  - The objective of this study was to evaluate the correlation between urine and
      serum benzoylecgonine (BE) levels in pregnant women who use crack cocaine. Ten
      women who had recently smoked crack cocaine were recruited from a prenatal
      substance abuse clinic to participate in this study. Urine and serum were
      obtained concurrently for quantitative determination of BE, (the major metabolite
      of cocaine), using gas chromatography/mass spectrometry. Pearson correlation was
      used for statistical analysis. The median reported interval since most recent
      crack use was 35 hours (range 9.5 to 63 hr). The median gestational age of the
      subjects was 31 weeks (range 22 to 38 weeks). Urine benzoylecgonine levels ranged
      from 1038 ng/mL to 1,950,563 ng/mL and serum BE levels ranged from 2.5 to 3074.3
      ng/mL. Pearson correlation for urine and serum BE levels was 0.92, p < 0.001.
      This is the first study to report the correlation between urine and serum BE
      levels in pregnant women who use crack cocaine.

PMID- 9605251
TI  - Perinatal factors predicting severe intracranial hemorrhage.
AB  - The objective of this paper is to determine the importance of perinatal factors
      predicting occurrence of severe intracranial hemorrhage (ICH) in premature
      newborns. A post-hoc analysis of a previously published randomized, double
      blinded, prospective trial was performed. Logistic regression analysis was used
      to assess the importance of obstetrical variables and umbilical cord blood
      coagulation studies and acid-base status in predicting severe ICH (grades 3 and
      4). The trial lasted 42 months; 401 pregnant women were invited to participate
      and 48 declined. The most important predictors of severe ICH in order of
      decreasing significance were: gestational age at delivery (p=0.0001), duration of
      painful labor (p=0.0077), duration of antenatal antibiotic therapy (p=0.0203),
      maternal age (p=0.0247), and factor X activity in umbilical cord blood
      (p=0.0302). Mode of delivery, cord blood acid-base, and coagulation status did
      not correlate with severe ICH. The majority of severe ICHs were late in onset;
      only two of 31 were known to have occurred in the first 24 hr of life.
      Gestational age, duration of painful labor, duration of antibiotic therapy, and
      maternal age were the most important predictors of severe ICH.

PMID- 9605253
TI  - A case of mosaic tetrasomy 12p (Pallister-Killian Syndrome) diagnosed prenatally:
      comparison of chromosome analyses of various cells obtained from the patient.
AB  - A pregnant woman was referred to our hospital at the 29th week of gestation with
      the symptom of polyhydramnios; diaphragmatic herniation of the fetus was
      suspected. Fetal chromosome anlaysis was performed using fibroblasts obtained by
      aminocentesis, and mosaicism of 46,XX and isochromosome of 12p were diagnosed.
      Out of 50 karyotyped cells, 19 (38.0%) showed the tetrasomy of the isochromosome
      of 12p. The mother vaginally delivered a baby girl who died just after delivery.
      The analysis of cord blood lymphocytes revealed only 0.5% incidence of tetrasomy
      of 12p. The incidence of tetrasomy was 8.0% for the placental chorionic villi,
      48.0% for the fibroblasts obtained from the umbilical cord, and 70.0% for the
      skin fibroblasts. Thus, the diagnosis of Pallister-Killian Syndrome (PKS) is
      confirmed by mosaicism of i(12p), that is, the affected patients exhibit tissue
      specific mosaicism, with the abnormal karyotype expression in limited
      lymphocytes, but marked in fibroblasts.

PMID- 9605254
TI  - Hereditary cholestasis with lymphoedema (Aagenaes syndrome, cholestasis
      lymphoedema syndrome). New cases and follow-up from infancy to adult age.

PMID- 9605255
TI  - Aspirin-induced gastritis, like Helicobacter pylori-induced gastritis disinhibits
      acid secretion in humans: relation to cytokine expression.
AB  - BACKGROUND: Helicobacter pylori infection contributes to hypergastrinemia and
      hypersecretion of acid by blocking inhibitory reflex pathways to gastrin and
      parietal cells normally activated by antral distention. Our aim was to
      investigate whether a similar blockade of inhibitory responses could be provoked
      by inducing gastritis with aspirin, thus implicating a common inflammatory
      component, possibly a proinflammatory cytokine(s). METHODS: We studied the
      effects of antral distention on stimulated acid secretion and gastrin release in
      H. pylori-negative volunteers, before and after 3 days of aspirin therapy (2 g
      daily). Immediately before the examinations, the severity of gastric mucosal
      injury was evaluated macroscopically and histologically, and the production of
      interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha, and
      interferon (IFN)-gamma was determined by immunohistochemistry. RESULTS: Most
      subjects had severe gastric injury after aspirin therapy, resulting in a
      substantially increased production of IL-1beta, IL-6, and IL-8 but not of TNF
      alpha and IFN-gamma in the antral mucosa. In these subjects the acid-inhibitory
      response was abolished or markedly reduced. Conversely, aspirin therapy failed to
      affect the gastrin release in all subjects studied. CONCLUSIONS: The
      disinhibition of acid secretion in response to antral distention is a joint
      feature of the gastritis induced by aspirin and H. pylori infection, possibly
      related to the increased production of IL-1beta, IL-6, and IL-8. The H. pylori
      related hypergastrinemia apparently has a different background.

PMID- 9605256
TI  - Effect of Helicobacter pylori infection on gastric juice pH.
AB  - BACKGROUND: How Helicobacter pylori infection affects gastric acid secretion is
      still unclear. METHODS: Gastric juice pH, ammonia concentration in gastric juice,
      serum gastrin level, and grade of gastritis in accordance with the Sydney System
      were determined for patients with gastric ulcer (GU) and duodenal ulcer (DU)
      before and after treatment with lansoprazole and amoxicillin, and results were
      compared with those of H. pylori-negative controls. RESULTS: Scores for H. pylori
      density, atrophy, metaplasia, and activity of gastritis in the corpus were higher
      in patients with GU, especially those with proximally located GU, than in those
      with DU. Gastric juice pH was significantly higher in GU patients than in DU
      patients and controls. After H. pylori eradication, gastric juice pH and serum
      gastrin levels in both GU and DU patients were significantly decreased to control
      levels. In patients without eradication, no significant changes in these factors
      were observed. CONCLUSIONS: These findings suggest that H. pylori infection and
      gastritis in the corpus suppress acid secretion and increase gastric juice pH,
      resulting in hypergastrinemia, and that eradication of H. pylori normalizes acid
      secretion and serum gastrin levels.

PMID- 9605262
TI  - Disappearance of gastric mucosa-associated lymphoid tissue in coeliac patients
      after gluten withdrawal.
AB  - BACKGROUND: Mucosa-associated lymphoid tissue (MALT) develops in gastric mucosa
      in response to chronic antigenic stimulation, such as Helicobacter pylori
      infection. However, reactive lymphoid follicles have been found also in the
      stomach of H. pylori-negative coeliac patients, suggesting that other
      environmental factors may be involved in MALT genesis. The aim of our study was
      to evaluate the effects of gluten withdrawal in H. pylori-negative coeliac
      patients with gastric MALT. METHODS: We studied 23 H. pylori-negative untreated
      coeliac patients with gastric MALT. All patients underwent determination of
      antigliadin (AGA) and antiendomysium antibodies (EMA) and upper endoscopy with
      multiple biopsies in duodenum, gastric corpus, and antrum. Lymphoid follicles and
      H. pylori status were assessed by histopathologic and enzymatic analysis. All
      patients were started on a gluten-free diet and were reevaluated after 12 months.
      To consider their adherence to the gluten-free diet we relied on direct patient
      questioning. Thirteen patients who had strictly adhered to the gluten-free diet
      constituted our study group. Ten patients who had not strictly adhered to gluten
      withdrawal from their diet constituted the control group. RESULTS: Regression of
      MALT was obtained in 9 of 13 (69%) patients who strictly followed the gluten-free
      diet; in the control group MALT disappeared in 2 of 10 (20%) patients (P=0.0361).
      DISCUSSION: Disappearance of reactive lymphoid follicles in the gastric mucosa of
      H. pylori-negative coeliac patients after gluten withdrawal suggests that
      antigens related to alimentary gluten may constitute persistent stimuli for
      development of gastric MALT in coeliac patients.

PMID- 9605261
TI  - Substance P in the gastrointestinal tract of non-obese diabetic mice.
AB  - BACKGROUND: Gut dysmotility occurs in most diabetics. Substance P is a
      neurotransmitter that plays an important role in regulating gastrointestinal
      motility. The present investigation was carried out to evaluate the possible role
      of this neurotransmitter in the pathogenesis of dysmotility in diabetics.
      METHODS: Pre-diabetic and diabetic female non-obese diabetic (NOD) mice aged 22
      24 weeks were studied. As controls, BALB/CJ mice of the same age and sex were
      used. Substance P concentrations in tissue extracts from the antrum, duodenum,
      and colon were determined with radioimmunoassay. Substance P-immunoreactive nerve
      elements and endocrine cells were identified by immunocytochemistry and
      quantified with computerized image analysis. RESULTS: Substance P levels in the
      antrum of both pre-diabetic and diabetic NOD mice were significantly lower than
      those of controls. In the duodenum and colon substance P levels were higher than
      those of the controls in both pre-diabetics and diabetic NOD mice. The relative
      volume density of substance P-immunoreactive nerve fibres in the colon of
      diabetic NOD mice was significantly decreased. There was no statistically
      significant difference between pre-diabetic and diabetic NOD mice and controls
      with regard to the relative volume density of substance P immunoreactive nerve
      fibres in the antrum and duodenum. In the antrum the number of substance P
      immunoreactive cells decreased significantly in both pre-diabetic and diabetic
      NOD mice. In the duodenum and colon the numbers of these cells in NOD mice did
      not differ from those of controls. CONCLUSIONS: The changes in substance P
      contents in various parts of the gastrointestinal tract of NOD mice seem to be
      primary to the onset of diabetes. The decreased antral substance P contents in
      NOD mice seems to be caused by structural change in the mucosal endocrine cells.
      In the small and large intestine the increase in substance P levels appears to be
      caused by change in the physiologic activities of the nerve element and/or
      endocrine cells rather than by structure changes. The abnormalities observed here
      in an animal model for diabetes type I might have relevance for the
      gastrointestinal dysmotility displayed in human diabetes.

PMID- 9605258
TI  - A rat model of chronic Helicobacter pylori infection. Studies of epithelial cell
      turnover and gastric ulcer healing.
AB  - BACKGROUND: Our aim was to infect rats with Helicobacter pylori and to study the
      effects of the infection on the gastric mucosa in normal and in ulcer-operated
      rats. METHODS: A mouse-adapted H. pylori (cagA-, VacA-) strain was inoculated
      into 23 rats. Another 20 uninfected rats served as controls. Two months later a
      gastric ulcer was induced in some rats. The animals were killed 3, 6, or 15 days
      after the ulcer operation. Tissues were taken for histology and for culture of H.
      pylori. Serum antibodies were determined. RESULTS: All inoculated rats were
      infected by H. pylori after 2 months, mainly in the antrum. In these rats a mild
      to moderate chronic inflammation and a significantly increased frequency of
      apoptotic cells were observed in the antrum and in the ulcer margin, the ulcer
      healing was delayed, and the serum level of H. pylori-specific Ig was increased.
      CONCLUSIONS: H. pylori infection in rats was successful and was accompanied by a
      mild to moderate mucosal inflammation. Gastric ulcer healing was delayed in
      infected rats, probably due to the inflammation and the increased apoptosis in
      epithelium.

PMID- 9605257
TI  - Accuracy of seven different tests for the diagnosis of Helicobacter pylori
      infection and the impact of H2-receptor antagonists on test results.
AB  - BACKGROUND: In this study we compared the accuracy of seven diagnostic tests in
      diagnosing Helicobacter pylori infection. METHODS: Over 1 year 351 consecutive
      dyspeptic patients were tested for H. pylori infection by means of antral biopsy
      specimens for the rapid urease test (RUT), culture, microscopy (acridine stain),
      and the laboratory urease test (LUT) and, in addition, with 14C urea breath test
      (UBT), IgG serology, and IgA serology (Orion Diagnostica Pyloriset New EIA-G and
      New EIA-A). The criterion for H. pylori infection was a minimum of three positive
      tests. Before being tested, 38% of the patients had used an H2-receptor
      antagonist (H2RA). RESULTS: Two-hundred and twenty-four patients (64%) were H.
      pylori-positive. The sensitivity and specificity of the tests were as follows
      (percentages): RUT, 85, 99; culture, 93, 100; microscopy, 81, 98; LUT, 80, 100;
      UBT, 95, 95; IgG serology, 99, 91; and IgA serology, 88, 91. The accuracy of the
      RUT and LUT was reduced in patients receiving H2RA therapy (P=0.04 and 0.01,
      respectively). CONCLUSIONS: Culture, UBT, and IgG serology were all superior to
      the other four tests in diagnosing H. pylori infection. Invasive urease-based
      tests were less accurate in patients receiving H2RAs.

PMID- 9605259
TI  - Processing-independent analysis in the diagnosis of gastrinomas.
AB  - BACKGROUND: This study evaluates whether a new analytic principle, processing
      independent analysis (PIA), offers better specificity and sensitivity than the
      conventional gastrin radioimmunoassay in the diagnosis of gastrinomas. METHODS:
      Plasma concentrations of alpha-amidated gastrins and the total progastrin product
      were measured with radioimmunoassay and with PIA, respectively, in 512 samples
      taken for gastrin measurement and in a selected group of gastrinoma patients
      (n=10). RESULTS: Among the 512 patients were 9 with gastrinomas. In plasma from
      these patients the median degree of amidation (ratio of alpha-amidated gastrins
      to total progastrin product) was 75% (range, 25-98%), whereas in the other groups
      the medians varied from 41% to 86%. In the second group of gastrinoma patients
      all had a degree of amidation of less than 50%. CONCLUSIONS: In screening for
      gastrinomas PIA offered no diagnostic advantages in comparison with conventional
      gastrin radioimmunoassay. However, in selected patients who in spite of normal or
      slightly increased concentrations of amidated gastrins were still suspected of
      having gastrinoma, additional measurement of the total progastrin product showed
      incomplete processing of progastrin and thus proved helpful in establishing the
      diagnosis.

PMID- 9605263
TI  - Role of reactive oxygen species in Salmonella typhimurium-induced enterocyte
      damage.
AB  - BACKGROUND: Reactive oxygen species (ROS) are potent mediators of inflammatory
      cell-mediated tissue destruction and may be of pathophysiologic importance in
      Salmonella typhimurium-induced tissue damage. METHODS: In this study the ligated
      rat ileal loops were injected with Salmonella live culture or toxin. The ROS
      generation was detected by measuring the mucosal myeloperoxidase (MPO) activity;
      the enterocyte xanthine oxidase (XO) activity, and the chemiluminescence response
      of gut macrophages. The enterocyte damage was estimated by measuring the extent
      of lipid peroxidation and cell viability. RESULTS: Treatment with Salmonella live
      culture or toxin resulted in an increase in the mucosal MPO activity, the
      enterocyte XO activity, and the chemiluminescence response of macrophages.
      Treated loop enterocytes had an increased extent of lipid peroxidation and
      decreased cell viability. Cell viability was also decreased when the enterocytes
      were co-cultured with macrophages isolated from the treated loops. Lipid
      peroxidation decreased, and cell viability increased in the presence of
      superoxide dismutase (SOD) or catalase. CONCLUSIONS: The S. typhimurium-mediated
      intestinal infection is accompanied by an increased generation of ROS, which may
      induce the lipid peroxidation of the enterocyte membrane, thereby leading to a
      loss of cell viability.

PMID- 9605260
TI  - Implications of gastric topical bioactive peptides in ammonia-induced acute
      gastric mucosal lesions in rats.
AB  - BACKGROUND: Ammonia, one of the pathogenic factors in Helicobacter pylori-induced
      mucosal injury, induces acute mucosal lesions in the rat glandular stomach.
      METHODS: The effect of ammonia administered intragastrically on gastric peptides
      was investigated in urethane-anesthetized rats. RESULTS: Gastric mucosal lesions
      were observed 5 min after 0.3% ammonia (4 ml/kg, intragastrically).
      Immunoreactive endothelin-1 (ET-1) and immunoreactive thyrotropin-releasing
      hormone (TRH) concentrations in the gastric wall decreased significantly 2 min
      and 5 min after ammonia, respectively. A significant increase in gastric juice
      immunoreactive ET-1 and TRH levels was reciprocally observed. The severity of
      gastric mucosal injury and changes in gastric immunoreactive ET-1 and TRH
      concentrations were shown to be concentration-dependent 30 min after ammonia.
      Atropine (5 mg/kg, intraperitoneally, -20 min) prevented ammonia-induced injury
      accompanied by a block of changes in gastric immunoreactive ET-1 and TRH
      concentrations. BQ-485 (ET(A) receptor antagonist; 2 mg/kg, subcutaneously) also
      abolished ammonia-induced lesions and gastric immunoreactive TRH changes.
      CONCLUSIONS: These findings suggested that gastric ET-1 and TRH play a role in
      ammonia-induced gastric mucosal injury mediated via a muscarine and an ET(A)
      receptor.

PMID- 9605264
TI  - The influence of apoptosis on intestinal barrier integrity in rats.
AB  - BACKGROUND: Apoptosis is a critical step responsible for maintaining the cellular
      balance between proliferation and death and for controlling tumorigenesis.
      Although an increase in intestinal apoptotic cells has been considered to be
      associated with the pathogenesis of gastrointestinal injury, little is understood
      concerning the role of apoptosis in the development of intestinal barrier
      dysfunction. METHODS: Apoptosis induced by intraperitoneal injection of
      doxorubicin in rats was evaluated by transmission electron microscopy and the
      TUNEL histochemistry method. Treatment with deoxy-D-glucose (a glycolytic pathway
      inhibitor) or cycloheximide (a protein synthesis inhibitor) was performed after
      doxorubicin challenge. Passage of human serum albumin from blood to the
      intestinal interstitium and the intestinal lumen or from the intestine to the
      intestinal interstitium and blood was evaluated by means of albumin clearance.
      RESULTS: A significant increase in gut water content, albumin flux, and
      bidirectional clearance of albumin accompanied by apoptotic epithelial cell
      increase was noted in doxorubicin-challenged rats treated with saline. The
      increase in endothelial and epithelial permeability and the increase of apoptosis
      could partly be prevented by treatment with deoxy-D-glucose or cycloheximide.
      CONCLUSION: Doxorubicin-increased epithelial apoptosis within the intestine
      occurs simultaneously with increased bidirectional permeability of the intestinal
      barrier, probably associated with both glycolytic and protein synthesis pathways.
      Apoptosis may thus play a role in the pathogenesis of intestinal barrier
      dysfunction.

PMID- 9605269
TI  - Gallbladder motility after duodenum-preserving resection of the pancreas head.

PMID- 9605265
TI  - Low symptomatic load in Crohn's disease with surgery and medicine as
      complementary treatments.
AB  - BACKGROUND: The treatment of Crohn's disease has changed owing to the recognition
      of its chronicity. Medical maintenance treatment and limited resections have
      evolved as major concepts of management, regarded as complementary, and both aim
      at reducing the symptoms. METHODS: We investigated the symptomatic load in
      Crohn's disease as reflected in a cross-sectional study of the symptom index,
      physicians' assessment, and the patients' perception of health. A cohort of 212
      patients from the primary catchment area and 125 referred patients were studied.
      RESULTS: Of catchment area patients, 83% were receiving medication, and the
      annual rate of abdominal surgery was 5.7%. Corresponding figures for the referred
      patients were 82% and 10.3%. According to the symptom index, 87% of catchment
      area patients were in remission or had only mild symptoms; according to the
      physicians' assessment, 90% were. The patients' median perception of health was
      90% of perfect health according to the visual analogue scale. The figures were
      similar for referred patients, except that referrals were considered more
      diseased by the physician. CONCLUSION: The great majority of patients with
      Crohn's disease are able to live in remission or experience only mild symptoms.

PMID- 9605267
TI  - Role of interleukin-10 in a murine model of dextran sulfate sodium-induced
      colitis.
AB  - BACKGROUND: Increased production of proinflammatory cytokines is characteristic
      of both animal models of experimental colitis and human inflammatory bowel
      disease. This study was designed to characterize the functional role of
      interleukin (IL)-10 in a murine model of experimental colitis. METHODS: Cytokine
      profiles were analyzed in animals with dextran sulfate sodium-induced colitis.
      The effect of treatment with IL-10 or anti-IL-10 antibodies on colonic cytokine
      production in vitro and tissue damage in vivo were evaluated. RESULTS: After the
      induction of colitis, there was a time-dependent increase in tissue tumor
      necrosis factor-alpha and IL-1beta levels, followed by a peak of the IL-10 level.
      The production of tumor necrosis factor-alpha and IL-1beta by cultured colonic
      tissues was inhibited by addition of IL-10, and conversely, it was enhanced by
      anti-IL-10. Treatment with IL-10 resulted in a marked improvement in intestinal
      inflammation. Blocking endogenous IL-10 was found to cause a modest exacerbation
      of inflammation. CONCLUSIONS: These results show that IL-10 has a functional role
      in regulating colonic inflammation during experimental colitis.

PMID- 9605266
TI  - Listeria monocytogenes in Crohn's disease.
AB  - BACKGROUND: In an immunohistochemical study a higher rate of reactivity of
      intestinal tissues to the antibody against Listeria monocytogenes was reported in
      Crohn's disease as compared with controls. METHODS: Seventy-six intestinal
      tissues, either therapeutically resected or biopsied, from 31 patients with
      Crohn's disease, 20 with ulcerative colitis, and 21 with non-inflammatory bowel
      disease were studied. DNA extracted from intestinal tissues by proteinase K
      treatment was used for nested polymerase chain reaction (PCR), using two sets of
      primers. PCR products were analyzed with agarose gel electrophoresis and
      subsequent Southern blot analysis. RESULTS: Our amplification system could detect
      9 pg of L. monocytogenes DNA. L. monocytogenes was detected in only one sample,
      that from a patient with ulcerative colitis. CONCLUSIONS: Our study does not
      support the etiologic significance of L. monocytogenes in Crohn's disease.

PMID- 9605270
TI  - Surgical-site infections after coronary artery bypass graft surgery:
      discriminating site-specific risk factors to improve prevention efforts.

PMID- 9605271
TI  - Comparison of vancomycin and cefuroxime for infection prophylaxis in coronary
      artery bypass surgery.
AB  - OBJECTIVE: To investigate clinically significant differences between vancomycin
      and cefuroxime for perioperative infection prophylaxis in coronary artery bypass
      surgery. DESIGN: A total of 884 patients were randomized prospectively to receive
      either cefuroxime (444) or vancomycin (440) and were assessed for infectious
      complications during hospitalization and 1 month postoperatively. SETTING: A
      university hospital. RESULTS: The overall immediate surgical-site infection rate
      was 3.2% in the cefuroxime group and 3.5% in the vancomycin group (difference, 
      0.3; 95% confidence interval, -2.6-2.1). CONCLUSIONS: The data suggest that
      vancomycin has no clinically significant advantages over cephalosporin in terms
      of antimicrobial prophylaxis. We suggest that cefuroxime (or first-generation
      cephalosporins, which were not studied here) is a good choice for infection
      prophylaxis in connection with coronary artery bypass surgery in institutions
      without methicillin-resistant Staphylococcus aureus problems. In addition to the
      increasing vancomycin-resistant enterococci problem, the easier administration
      and usually lower price of cefuroxime make it preferable to vancomycin.

PMID- 9605268
TI  - Predictive factors influencing the therapeutic response to diuretic treatment of
      ascites in nonazotemic cirrhotic patients.
AB  - BACKGROUND: A low-sodium diet and diuretics, although widely used, are not always
      the most satisfactory therapy for treatment of ascites in nonazotemic patients
      with liver cirrhosis. The objective of this investigation was to analyze various
      predictive factors influencing the therapeutic response to diuretic treatment of
      ascites in these patients. METHODS: Twenty-seven patients with nonazotemic liver
      cirrhosis and ascites were initially treated with spironolactone, 200 mg/day. If
      no response was observed, furosemide was added at 40-120 mg/day. Before and
      during the diuretic therapy 30 clinical and laboratory variables were
      investigated as possible predictive factors influencing the therapeutic response
      to diuretics. The renal arterial resistive index (RI) (reflecting renal vascular
      resistance) was estimated with duplex Doppler ultrasonography. RESULTS: Sixteen
      of the 27 patients (59%) responded to spironolactone alone, whereas 6 patients
      (22%) responded to combined diuretic therapy with spironolactone and furosemide.
      Five patients (19%) did not respond to diuretic treatment. Eight of the 30
      variables analyzed were statistically significant as possible predictive factors
      influencing the diuretic response: previous episodes of ascites and
      gastrointestinal hemorrhage, the presence of peripheral edema, the amount of
      ascites, plasma renin activity, plasma aldosterone concentrations, urinary sodium
      excretion, and renal interlobar arterial RI. In all patients who had diuretic
      resistant ascites, renal interlobar arterial RI was greater than 0.70. Only 9% of
      patients who responded satisfactorily to diuretic therapy had interlobar arterial
      RI greater than 0.70. CONCLUSIONS: According to our results, consideration for
      combining the clinical findings with noninvasively measured renal arterial RI
      using duplex Doppler ultrasonography would be mandatory in identifying a subgroup
      of cirrhotic patients with ascites who are at high risk for diuretic
      unresponsiveness.

PMID- 9605272
TI  - Risk features for surgical-site infections in coronary artery bypass surgery.
AB  - OBJECTIVE: To identify preoperative and perioperative features that may lead to a
      risk of surgical-site infection (SSI) after coronary artery bypass surgery.
      DESIGN: 884 patients who underwent coronary artery bypass grafting in 1992 and
      1993 were studied. The associations between 23 preoperative and perioperative
      features and the presence of SSI at the donor site or in the chest area were
      evaluated by univariate analysis followed by multivariate logistic regression
      analysis. SETTING: A university hospital. RESULTS: 172 patients (19.5%) either
      had an SSI recorded before discharge or had received antibiotics prescribed for a
      suspected SSI during the 1-month surveillance period after discharge.
      Multivariate logistic regression analysis showed an extreme body mass index (BMI;
      P=.015), female gender (P=.023), and chronic obstructive pulmonary disease (COPD;
      P=.030) to be independent risk features for SSI. The donor site was infected in
      136 patients (15.4%), an event for which female gender (P=.003) was the only
      independent risk feature. Forty-seven patients (5.3%) had an SSI of the chest
      area, with diabetes (P=.003) and extreme BMI (P=.010) as independent risk
      features. CONCLUSION: Extreme BMI, female gender, and COPD are highly significant
      independent predictors of the development of SSI. Female gender is a risk feature
      specifically for SSI at the donor site, whereas diabetes and extreme BMI predict
      it in the chest area.

PMID- 9605273
TI  - Vancomycin control measures at a tertiary-care hospital: impact of interventions
      on volume and patterns of use.
AB  - OBJECTIVE: Evaluate vancomycin prescribing patterns in a tertiary-care hospital
      before and after interventions to decrease vancomycin utilization. DESIGN:
      Before/after analysis of interventions to limit vancomycin use. SETTING: 420-bed
      academic tertiary-care center. INTERVENTIONS: Educational efforts began August
      10, 1994, and involved lectures to medical house staff followed by mailings to
      all physicians and posting of guidelines for vancomycin use on hospital
      information systems. Active interventions began November 15, 1994, and included
      automatic stop orders for vancomycin at 72 hours, alerts attached to the medical
      record, and, for 2 weeks only, computer alerts to physicians following each
      vancomycin order. Parenteral vancomycin use was estimated from the hospital
      pharmacy database of all medication orders. Records of a random sample of 344
      patients receiving vancomycin between May 1, 1994, and April 30, 1995, were
      reviewed for an indication meeting published guidelines. RESULTS: Vancomycin
      prescribing decreased by 22% following interventions, from 8.5 to 6.8 courses per
      100 discharges (P<.05). The estimated proportion of vancomycin ordered for an
      indication meeting published guidelines was 36.6% overall, with no significant
      change following interventions. However, during the 2 weeks that computer alerts
      were in place, 60% of vancomycin use was for an approved indication. CONCLUSIONS:
      Parenteral vancomycin prescribing decreased significantly following
      interventions, but the majority of orders still were not for an indication
      meeting published guidelines. Further improvement in the appropriateness of
      vancomycin prescribing potentially could be accomplished by more aggressive
      interventions, such as computer alerts, or by targeting specific aspects of
      prescribing patterns.

PMID- 9605274
TI  - Total and attributable costs of surgical-wound infections at a Canadian tertiary
      care center.
AB  - OBJECTIVE: To determine the total and attributable costs of surgical-wound
      infections in a Canadian teaching hospital. DESIGN: Retrospective incidence
      series study with chart review and examination of resource utilization
      attributable to wound infection. The charts of inpatients with wound infections
      were examined using the Appropriateness Evaluation Protocol (AEP), a validated
      chart review instrument designed to determine appropriateness of care, modified
      for wound infections. SETTING: A university referral center in Canada. PATIENTS:
      Medical records were abstracted from patients with wound infections who underwent
      an inpatient clean or clean-contaminated procedure during 1991. MEASUREMENTS:
      During the wound-infection treatment period, the hospital costs associated with
      providing care were tabulated for all inpatient days and for outpatient and
      emergency visits. Costs taken into account included nursing salary and benefits,
      nonphysician professional services, operating room time, laboratory, pharmacy,
      supplies, ancillary tests, and hotel costs. RESULTS: We identified 108 wound
      infections. Twenty-two patients required 28 surgical procedures related to a
      wound infection. Inpatient days totalled 1,116, costing $394,337. Fifty-five
      emergency and 42 clinic visits occurred, costing $27,193. By applying the AEP to
      the inpatient days, 833 days, or 10.2 days per case, were directly attributable
      to the wound infection. The hospital costs for inpatient care attributable to
      wound infections were $321,533 in total, or $3,937 per infection. Costs were
      distributed as follows: nursing, 51%; hotel, 14%; pharmacy, 10%; laboratory, 9%;
      emergency and outpatient clinic, 6%; professional services, 5%; operating room,
      3%; and ancillary tests, 2%. CONCLUSIONS: Wound infections contribute markedly to
      extra days of hospitalization and related costs. The AEP method is applied easily
      to determine attributable days of care and costs of wound infections, which are
      necessary to calculate the cost-benefit of infection control programs.

PMID- 9605275
TI  - Comparing nosocomial infection rates among surgical intensive-care units: the
      importance of separating cardiothoracic and general surgery intensive-care units.
AB  - Among surgical intensive-care units (ICUs), we assessed differences in risk
      adjusted nosocomial infection rates between cardiothoracic (CT) and general
      surgery ICUs, using National Nosocomial Infection Surveillance data from 1987 to
      1995. Device-associated rates and average length of stay were significantly lower
      in CT ICUs. Comparisons of risk-adjusted nosocomial infection rates among CT ICUs
      should be made separately from rates from general surgery ICUs.

PMID- 9605276
TI  - Disinfection of hospital rooms contaminated with vancomycin-resistant
      Enterococcus faecium.
AB  - Sixteen percent of hospital room surfaces remained colonized by vancomycin
      resistant enterococci (VRE) after routine terminal disinfection. Disinfection
      with a new "bucket method" resulted in uniformly negative cultures. Conventional
      cleaning took an average of 2.8 disinfections to eradicate VRE from a hospital
      room, while only one cleaning was required with the bucket method.

PMID- 9605279
TI  - Postdischarge surgical-site surveillance.

PMID- 9605278
TI  - Progress of US hospitals in implementing TB control programs.

PMID- 9605280
TI  - Surveillance of unexplained illness and death.

PMID- 9605283
TI  - Historical aspects of the study of malformations in The Netherlands.
AB  - The collection of malformed ("teratological") specimens of man and other mammals
      of Gerardus Vrolik (1775-1859) and his son Willem Vrolik (1801-1863), dating from
      the beginning of the 19th century, continues to function as a central part of the
      Department of Anatomy and Embryology in the Academic Medical Center at the
      University of Amsterdam. Recently, many specimens in the collection were
      reexamined, using radiographic, CT scan, and MRI methods. In order to provide
      background information concerning Dutch teratological research and anatomical
      cabinets, some aspects of the history of Dutch morphology during the 17th-19th
      centuries are briefly described in this paper. Special attention is paid to the
      scientific work and cabinet of Frederik Ruijsch (1638-1731), who sold this
      cabinet to Czar Peter the Great; Bernard Siegfried Albinus (1697-1770); Wouter
      van Doeveren (1733-1783), Andreas Bonn (1738-1818), and Sebald Justinus Brugmans
      (1763-1819), who sold or donated parts of their collections of malformed
      specimens to Leiden University; Petrus Camper (1722-1789) and Jan Bleuland (1756
      1838), whose collections are still in the Department of Anatomy at Groningen
      University and the Departments of Anatomy and Pathology of Utrecht University;
      and Gerard and Willem Vrolik.

PMID- 9605284
TI  - Congenital anomalies in the teratological collection of Museum Vrolik in
      Amsterdam, The Netherlands. I: Syndromes with multiple congenital anomalies.
AB  - The Museum Vrolik collection of the Department of Anatomy and Embryology of the
      University of Amsterdam, founded by Gerardus Vrolik (1775-1859) and his son
      Willem Vrolik (1801-1863), consists of more than 5,000 thousand specimens of
      human and animal anatomy, embryology, pathology, and congenital anomalies.
      Recently, the collection of congenital anomalies was recatalogued and redescribed
      according to contempory syndromological views. The original descriptions, as far
      as preserved, were compared with the clinical and radiographical findings. In 13
      specimens the following multiple congenital anomalies (MCA) syndromes were
      diagnosed: acrofacial dysostosis, Apert syndrome, Brachmann-De Lange syndrome,
      ichthyosis congenita gravis, Jarcho-Levin syndrome, Meckel syndrome, oro-facio
      digital syndrome type IV, Roberts syndrome, Smith-Lemli-Opitz syndrome, Treacher
      Collins syndrome, and trisomy 13. It appeared that the founders of the museum
      studied and described several of these syndromes many years before they became
      established as such. In some specimens a reliable diagnosis is still pending. The
      use of additional diagnostical techniques, such as MRI, CT scanning, and
      fluorescence in situ hybridization, in these specimens is currently being
      investigated.

PMID- 9605277
TI  - Statistical quality control methods in infection control and hospital
      epidemiology, Part II: Chart use, statistical properties, and research issues.
AB  - This is the second in a two-part series discussing and illustrating the
      application of statistical process control (SPC) in hospital epidemiology. The
      basic philosophical and theoretical foundations of statistical quality control
      and their relation to epidemiology are emphasized in order to expand the mutual
      understanding and cross-fertilization between these two disciplines. Part I
      provided an overview of the philosophy and general approach of SPC, illustrated
      common types of control charts, and provided references for further information
      or statistical formulae. Part II now discusses alternate possible SPC approaches,
      statistical properties of control charts, chart-design issues and optimal control
      limit widths, some common misunderstandings, and more advanced issues. The focus
      of both articles is mostly nonmathematical, emphasizing important concepts and
      practical examples rather than academic theory and exhaustive calculations.

PMID- 9605281
TI  - SHEA's response to proposed OSHA TB exposure rule.

PMID- 9605287
TI  - Segregation analysis in nonsyndromic holoprosencephaly.
AB  - Holoprosencephaly (HPE) is a developmental defect due to a failure of cleavage of
      the forebrain. The brain malformations are usually associated with facial
      anomalies. From a series of 258 HPE records involving at least one affected
      child, 97 cases in 79 families with nonsyndromic and nonchromosomal HPE were
      selected. The male:female ratio was 0.87. A high degree of familial aggregation
      was observed in 23/79 families (29%). A segregation analysis performed in the 79
      nuclear families led to the conclusion that the transmission of nonsyndromic HPE
      is compatible with an autosomal dominant mode of inheritance. Under this
      hypothesis, the penetrance was estimated as 82% for major types (alobar,
      semilobar, lobar) and 88% when major and minor types (atypical) were included.
      The proportion of sporadic cases was estimated to be 68%. This genetic model
      allows a prediction of the recurrence risk after an isolated case of 13% for
      major types and 14% when minor types are included.

PMID- 9605285
TI  - Congenital anomalies in the teratological collection of Museum Vrolik in
      Amsterdam, The Netherlands. II: Skeletal dysplasias.
AB  - The Museum Vrolik collection of the Department of Anatomy and Embryology of the
      University of Amsterdam, founded by Gerardus Vrolik (1775-1859) and his son
      Willem Vrolik (1801-1863), consists of more than five thousand specimens of human
      and animal anatomy, embryology, pathology, and congenital anomalies. Recently,
      the collection of congenital anomalies was recatalogued and redescribed according
      to contempory syndromological views. The original descriptions, as far as
      preserved, were compared with the clinical and radiographical findings. In 18
      specimens the following skeletal dysplasias were diagnosed: achondrogenesis,
      achondroplasia, Blomstrand chondrodysplasia, Majewski syndrome, osteodysplastic
      primordial dwarfism, osteogenesis imperfecta type I, osteogenesis imperfecta type
      II, and thanatophoric dysplasia with and without cloverleaf skull. Radiography
      did not yield a diagnosis in 4 specimens. The use of additional diagnostical
      techniques, such as MRI and CT scanning and fluorescence in situ hybridization in
      these specimens, is currently being investigated.

PMID- 9605286
TI  - Novel transthyretin missense mutation (Thr34) in an Italian family with
      hereditary amyloidosis.
AB  - We report on the genetic and molecular characterisation of an Italian family with
      a late-onset, autosomal dominant transthyretin amyloidosis. The transthyretin
      gene was analysed by polymerase chain reaction (PCR), restriction generating PCR,
      and sequencing, allowing us to discover in one allele a novel point mutation. It
      consists of a G to C transversion at position 1692 of the genomic sequence,
      leading to a Thr for Arg substitution at the position 34 of the polypeptidic
      chain. This mutation is associated with a severe sensory-motor peripheral
      neuropathy and a restrictive cardiomyopathy.

PMID- 9605289
TI  - Medullary cystic kidney disease with hyperuricemia and gout in a large Cypriot
      family: no allelism with nephronophthisis type 1.
AB  - We describe a large Cypriot family with an interstitial type of nephropathy,
      inherited as an autosomal dominant trait that led to end stage renal failure
      between 51 to 78 years of age (mean 62.2 years). Twenty-three people are known to
      be affected, but several younger relatives with normal renal function may remain
      undiagnosed because of the absence of precise clinical and laboratory diagnostic
      criteria. This nephropathy is associated with medullary renal cysts,
      hypertension, hyperuricemia, and gout. Several relatives have typical medullary
      cystic disease (MCD), while in the others the findings are compatible with this
      diagnosis. Due to the similarity of clinical and pathologic findings, earlier
      reports had suggested that MCD may be allelic to autosomal recessive familial
      juvenile nephronophthisis, which was mapped recently to chromosome band 2q13.
      Linkage analysis of the present family with a closely linked marker excluded
      linkage to the above locus. Linkage was also excluded to the PKD1 locus of adult
      polycystic kidney disease type 1, and up to 5 cM on either side, on chromosome
      16. We suggest that because of the element of hyperuricemia and gout found in
      this family, although with reduced penetrance, it may represent a variant of
      autosomal dominant MCD of the adult type. This variability may be the result of
      allelic or locus heterogeneity. Molecular genetic approaches including linkage
      analysis on appropriate families will certainly assist in classifying such
      related genetically heterogeneous disorders.

PMID- 9605294
TI  - Craniosynostosis and marfanoid habitus without mental retardation: report of a
      third case.

PMID- 9605291
TI  - Del(14)(q22.1q23.2) in a patient with anophthalmia and pituitary hypoplasia.
AB  - Only few cases with an interstitial deletion of chromosome 14 have been described
      so far. We report on a 21-month-old girl with an interstitial deletion of the
      long arm of chromosome 14, del(14)(q22.1q23.2). She presented with bilateral
      anophthalmia, absent left external auditory canal, facial asymmetry,
      microretrognathia, hypotonia, and psychomotor retardation. Skeletal X-rays showed
      lambdoid craniosynostosis, a very small sella turcica and cervical vertebral
      anomalies. Brain MRI showed the absence of the optic chiasm, an hypoplastic
      pituitary gland, and cortical atrophy. No cardiac or abdominal malformations were
      found. Two other patients with a similar deletion, (del(14)(q22.1q23) and
      del(14)(q22.1q22.3)), are described. Both presented with bilateral anophthalmia
      and absent pituitary or hypogonadism. These three cases suggest that the region
      14q22 is important for eye and pituitary development. Interestingly, the human
      BMP-4 gene, a member of the TGF-beta superfamily, maps to 14q22-q23 and may play
      a role in pituitary and eye development.

PMID- 9605282
TI  - Museums, antiquarian books, and modern teratology.

PMID- 9605290
TI  - The facioscapulohumeral muscular dystrophy (FSHD1) gene affects males more
      severely and more frequently than females.
AB  - We investigated 52 families of patients with facioscapulohumeral muscular
      dystrophy (FSHD1), including 172 patients (104 males and 68 females). Among 273
      DNA samples which were analyzed with probe p13E-11, 131 (67 males and 64 females)
      were shown to carry an EcoRI fragment smaller than 35 kb; 114 among them were
      examined clinically and neurologically. Results of the present investigation
      showed that: a) there is no molecular evidence for autosomal or X-linked
      recessive inheritance of FSHD1; b) an excess of affected males, which is
      explained by a significantly greater proportion of females than males among
      asymptomatic cases and a significantly greater proportion of affected sons than
      daughters observed in the offspring of asymptomatic mothers; c) the penetrance of
      the FSHD1 gene until age 30 was estimated as 83% for both sexes but was
      significantly greater for males (95%) than for females (69%); d) new mutations
      occur significantly more frequently in females than males among somatic/germinal
      mosaic cases; and e) severely affected cases originated more often through new
      mutations or were transmitted through maternal than through paternal lines
      including somatic/germinal mothers. These observations have important
      implications for understanding the molecular mechanisms responsible for FSHD1 and
      for genetic and prognostic counseling according to the gender of the affected
      patient.

PMID- 9605292
TI  - Heteroallelic monozygotic twins and triplets.

PMID- 9605293
TI  - Achondroplasia associated with Down syndrome.

PMID- 9605288
TI  - Vertical transmission of the Ohdo blepharophimosis syndrome.
AB  - Ohdo blepharophimosis syndrome (OBS) is a multiple congenital anomalies-mental
      retardation syndrome composed of blepharophimosis, ptosis, dental hypoplasia,
      partial deafness, and mental retardation. Previously reported cases of OBS have
      been sporadic except for the report by Ohdo et al. [1986, J Med Genet 23:242-244]
      that described two affected sisters and a first cousin favoring autosomal
      recessive inheritance. The original report by Ohdo et al. [1986] may reflect
      nonpenetrance of an autosomal dominantly inherited disorder or genetic
      heterogeneity of OBS. We report on a child and the mother who have
      blepharophimosis, ptosis, dental anomalies, mild hearing loss, and mental
      retardation. Chromosome analysis in both showed a balanced paracentric inversion
      of the long arm of chromosome 9, which was also present in two phenotypically
      normal sibs of the mother. This is the first report of vertical transmission of
      OBS suggestive of autosomal dominant inheritance. X-linked dominant and
      mitochondrial inheritance are other possible modes of inheritance.

PMID- 9605295
TI  - Who is responsible for making medical decisions?

PMID- 9605296
TI  - Impact of transfusion guidelines on neonatal transfusions.
AB  - BACKGROUND: Preterm infants with birth weights (BW) <1250 gm are given multiple
      blood transfusions either for replacement of blood loss or for correction of
      symptomatic anemia of prematurity. OBJECTIVE: To assess the effectiveness of
      transfusion guidelines in reducing the number of transfusions given to infants
      with BW <1250 gm. METHODS: This cohort study was conducted at the regional
      teaching medical center with level III obstetric and neonatal services. Preterm
      infants with BW <1250 gm and gestational age <32 weeks were admitted to the
      neonatal intensive care unit during a period of 6 months before and after
      implementation of transfusion guidelines. The final sample size constituted 39
      infants before guidelines (BG) and 41 infants after guidelines (AG). The primary
      outcome measure was the total number and volume of transfusions given per infant
      in the first 2 weeks of life and before discharge from the nursery. RESULTS: We
      observed a significant reduction in the mean number (4.7 to 2.7, p = 0.003) and
      volume (52 ml to 30 ml, p = 0.0005) of transfusions given per infant in the first
      2 weeks of life, as well as a definite trend toward reduction in the total number
      (10.5 to 8.0, p = 0.08) and volume (156 ml to 119 ml, p = 0.07) of transfusions
      given before discharge in the BG versus AG, respectively. When all the
      transfusions given to the 41 infants in the AG group were analyzed for compliance
      with guidelines, 96% (313 of 328) were observed to be in compliance. CONCLUSION:
      This study shows that transfusion guidelines are effective in decreasing the
      number of transfusion given to infants with BW <1250 gm. An indirect benefit of
      guidelines contributing to a reduced number of transfusions may be a heightened
      awareness to decrease blood losses.

PMID- 9605297
TI  - Role of renal ultrasonography in the management of pyelonephritis in pregnant
      women.
AB  - OBJECTIVE: The objective of this study was to determine the usefulness of renal
      ultrasonography in pregnant women with pyelonephritis. STUDY DESIGN: A
      retrospective review was done of hospital records of 171 consecutive pregnant
      women admitted to the hospital over a 7-year period with the diagnosis of
      pyelonephritis. RESULTS: Urine cultures were positive in all but one of the women
      and intravenous antibiotics were administered in all cases. Renal ultrasonography
      was done in 75 (43.9%) of the women and results found to be normal in 26 (34.7%)
      of them. The renal pelvis was dilated mildly (6 to 10 mm) in 25 (33.3%),
      moderately (11 to 15 mm) in 16 (21.3%), and severely (> or = 16 mm) in 8 (10.7%)
      patients. Duplicated collecting systems and renal calculi were each found in 2
      (2.7%) patients. All patients were treated conservatively with no need for
      ureteral stents. Three of the patients with severe hydronephrosis were first seen
      at term and delivery was therefore induced. There was no difference in maternal
      characteristics and outcome of pregnancy between women who underwent renal
      ultrasonography and those who did not. However, the duration of hospitalization
      was significantly longer (p < 0.02) for women in whom renal ultrasonography was
      performed (mean +/- SD, 5.8 +/- 1.7 vs 4.1 +/- 1.3 days). CONCLUSION: Renal
      ultrasonography is of limited benefit in pregnant women with pyelonephritis,
      because these imaging studies only rarely modify management and do not
      significantly affect pregnancy outcome.

PMID- 9605298
TI  - Survival and subsequent outcome to five years of age for infants with birth
      weights less than 801 grams born from 1983 to 1989.
AB  - OBJECTIVE: To determine the neurodevelopmental status for 5-year-old survivors
      with birth weights (BW) <801 gm born in the 1980s and to assess differences in
      outcome for those born from 1986 to 1989 compared with those born from 1983 to
      1985. STUDY DESIGN: This investigation was a longitudinal follow-up of all
      infants with BW from 450 to 800 gm born at one of two hospitals in Kansas City,
      Mo., between January 1983 and December 1989. Medical records were reviewed at
      discharge to determine obstetric and neonatal interventions and complications.
      Neurodevelopmental outcome was assessed by a multidisciplinary evaluation at 60
      +/- 3 months old. Multiple logistic regression analyses were used to determine
      factors statistically associated with survival and long-term outcome. RESULTS:
      The percentage of infants surviving to hospital discharge was not different
      between periods. From 1986 to 1989, there were more infants with BW <601 gm and
      <26 weeks' gestational age. Survival was greater for gestational age categories >
      or = 24 weeks. BW, gestational age, female gender (p < 0.0001), and birth era (p
      < 0.01) were each independently significantly associated with improved survival.
      At 5 years of age, there were no significant outcome differences between birth
      era cohorts. Overall, approximately 21% of infants had severe disabilities. Long
      term outcome was significantly influenced by the occurrence of intracranial
      hemorrhage and socioeconomic status. CONCLUSION: For infants with BW <801 gm,
      survival of infants > or = 24 weeks' gestational age was greater in 1986 to 1989
      compared with 1983 to 1985, although the 5-year neurodevelopmental outcome was
      not different between groups. The significant impact of social risk status on
      outcome suggests that factors outside the intensive care nursery must be
      addressed to improve long-term outcome.

PMID- 9605299
TI  - Accuracy of primary bedside neonatal nurse-generated score for neonatal acute
      physiology (SNAP) scores.
AB  - OBJECTIVE: To determine whether 24-hour SNAP scores generated from data gathered
      by primary bedside nurses agreed with the SNAP scores of one trained research
      nurse. STUDY DESIGN: Primary bedside nurses (n = 50) in a level III private
      nursery collected data necessary for generating 24-hour SNAP scores on 60
      consecutively admitted inborn neonates who lived at least 24 hours. The amount of
      time required for data collection and scoring was also determined. SNAP scores
      and the time required to generate them were compared with the unit research
      nurse's SNAP scores and time required to generate them on the same 60 patients.
      The Wilcoxon rank test and Spearman's rank correlation were used for statistical
      analyses. RESULTS: SNAP scores generated from primary bedside nursing data did
      not differ from those of the research nurse's SNAP scores (11.7 +/- 0.8 vs 11.4
      +/- 0.9 [mean +/- SEM], p = 0.7), and they correlated well over a wide range of
      SNAP scores (r = 0.93, p = 0.0001). Primary bedside nurses required more time (15
      +/- 0.7 vs 3.0 +/- 0.08 minutes, p = 0.0001) to generate SNAP scores than the
      research nurse. CONCLUSION: Primary bedside level III nurses can accurately
      obtain data for SNAP scores during 8- to 12-hour shifts.

PMID- 9605300
TI  - Nosocomial sepsis in the neonatal intensive care unit.
AB  - OBJECTIVE: To evaluate the risk factors for nosocomial sepsis among infants
      hospitalized in 23 neonatal intensive care units. METHODS: Risk factors for
      nosocomial sepsis among 5760 admissions are analyzed by birth weight groups, <1
      kg, 1 to 1.5 kg, and >1.5 kg. A Cox hazard regression model was used to evaluate
      further detail in the two lower weight groups. RESULTS: Use of corticosteroids
      had no effect on the incidence of nosocomial sepsis in the two lower weight
      categories although it was significant among the >1.5 kg infants. In a simple Cox
      model, significant risk factors included lowest birth weight category,
      ventilatory support, and presence of a central venous catheter. The complex Cox
      model revealed that an increase in total days of presence of central arterial
      catheter, use of antibiotics, and ventilatory support were significant but that
      total days of presence of a central venous catheter was not. A model for Candida
      sepsis revealed as a risk factor an increase in total days of use of antibiotics
      before infection. CONCLUSIONS: The risk for infection associated with presence of
      a central venous catheter is the same for each day of exposure (i.e., the same
      risk on day 5 of presence of the line as on day 30), but the risk associated with
      ventilatory support increases over time. Candida sepsis is associated with
      prolonged antibiotic use before the first episode of nosocomial sepsis and not
      with birth weight group.

PMID- 9605301
TI  - Perinatal toxicology screening: comparison of various maternal and neonatal
      samples.
AB  - OBJECTIVES: Because cocaine metabolites are concentrated in amniotic fluid, we
      designed this study to assess the usefulness of amniotic fluid and that of
      neonatal gastric aspirate for perinatal drug screening and to compare the
      concentration of cocaine metabolites in various maternal and neonatal specimens.
      STUDY DESIGN: We compared the reliability of various maternal and neonatal
      specimens for detecting drug exposure and the concentration of cocaine
      metabolites in these specimens. RESULTS: Our data showed that screening for
      perinatal drug abuse with any single specimen leads to false-negative results.
      Drug screening with neonatal amniotic fluid, gastric aspirate, or cord blood did
      not improve the reliability of perinatal drug screening. CONCLUSION: Testing more
      than one type of body fluid may increase the reliability of perinatal drug
      screening.

PMID- 9605307
TI  - Evaluation of neonates born with intrauterine growth retardation: review and
      practice guidelines.
AB  - Intrauterine growth retardation affects approximately 10% of live-born infants.
      Causes of intrauterine growth retardation are heterogeneous, and frequently the
      care of these infants poses a diagnostic and therapeutic challenge. Diagnosis of
      impaired fetal growth is an area in which close collaboration among the
      obstetrician, pediatrician, and dysmorphologist is essential for proper care of
      these newborns. It is axiomatic that the best way to care for these infants is to
      establish an accurate diagnosis prenatally or soon after birth and to manage on
      that basis. An algorithm for evaluation and management of intrauterine growth
      retardation that is based on available empiric data is presented. These
      guidelines are intended to guide medical practice and not to replace clinical
      judgment.

PMID- 9605303
TI  - Establishing a noise measurement protocol for neonatal intensive care units.
AB  - OBJECTIVES: To compare three noise exposure measurement methods and determine the
      effect of location within the nursery, time of day, day of week, shift, and
      activities such as nursing shift change and physicians' rounds on noise
      measurements. STUDY DESIGN: We performed a noise distribution survey, central
      site measurements, and quadrant area measurements in our nursery. The
      measurements made were sound pressure level and hourly LEQ, LMAX, and L10.
      RESULTS: The noise distribution survey method was least useful because steady
      state noise sources were the exception. Differences between central site and
      quadrant area measurements were minimal. There was no significant effect of time
      of day, shift change, or physician rounds on the noise measurements. CONCLUSIONS:
      In an open nursery with excessive noise levels central site measurements over a
      relatively short time accurately reflect the noise exposure. A protocol for
      measuring noise exposure in the neonatal intensive care unit is appended.

PMID- 9605305
TI  - Placental blood sampling: an aid to the diagnosis of neonatal sepsis.
AB  - OBJECTIVE: To determine the usefulness of placental blood cultures in
      establishment of the diagnosis of early onset sepsis. STUDY DESIGN: Babies born
      to mothers with suspected intraamniotic fluid infection had blood cultures
      obtained from a branch of the umbilical vein on the fetal surface of the placenta
      immediately after delivery. The babies at highest risk (n = 35) had subsequent
      neonatal blood cultured from a peripheral vein (group 1), whereas 26 newborns at
      a lower risk did not (group 2). A group of 20 term babies born after
      uncomplicated labor and vaginal delivery or by elective cesarean delivery served
      as control subjects. RESULTS: Placental blood cultures were more often positive
      for pathogens in group 1 (7 of 35; 20%; 0.09 to 0.36) than in group 2 (0 of 26; 0
      to 0.11) or control subjects (0 of 20; 0 to 0.14; p < 0.02). Within group 1,
      placental blood cultures were more often positive (7 of 35; 20%; 0.09 to 0.36)
      than subsequent neonatal blood cultures (1 of 35; 3%; 0 to 0.15; p < 0.05).
      Contaminants were cultured in 3 of 81 (4%; 01 to 0.11) placental samples (all
      from group 1) compared with 1 of 35 (3%; 0 to 0.11) neonatal samples (difference
      not significant). CONCLUSIONS: A carefully obtained culture of placental blood
      may be a useful addition or substitute for neonatal blood culturing in newborns
      at risk for early-onset sepsis by virtue of maternal risk factors.

PMID- 9605306
TI  - C-reactive protein levels in the extremely premature infant: case studies and
      literature review.
AB  - Sepsis continues to be a significant source of morbidity and mortality in the
      neonatal intensive unit. At the same time, we need to contain medical costs and
      prevent the rapid growth of resistant organisms by limiting unnecessary
      antibiotic use. Among laboratory indexes studied as indirect indicators of the
      presence and resolution of infection and inflammation, C-reactive protein (CRP)
      has gained more recent widespread use. CRP usually increases in a delayed manner
      with the onset of inflammation and decreases as inflammation resolves. We follow
      serial CRP values in our neonatal intensive care unit from the start of a sepsis
      evaluation until antibiotic therapy is withdrawn. We describe two extremely low
      birth weight patients who improved clinically with therapy and whose CRP levels
      normalized in the face of continued positive blood cultures. The implications for
      the use of CRP in deciding when to halt therapy in premature infants are
      discussed.

PMID- 9605302
TI  - Labor and delivery in nulliparous women who present with an unengaged fetal head.
AB  - OBJECTIVE: We assessed the relation of fetal station in early labor to subsequent
      patterns of dilation and descent and to the probability of cesarean delivery.
      STUDY DESIGN: We evaluated 132 nulliparous women who were in spontaneous latent
      phase labor with singleton, vertex-presenting, term fetuses. For each
      participant, pertinent variables relating to labor characteristics and mode of
      delivery and newborn characteristics were recorded. Labor curves were drawn and
      analyzed. RESULTS: Of the 132 participants, 29 (22%) presented with an engaged
      fetal head, and 103 (78%) presented with an unengaged fetal head. In the
      unengaged group, 15 (11%) presented with a floating fetal head (-3 station or
      above), and 88 (67%) presented with a dipping fetal head (-2 or -1 station). A
      floating head in latent-phase labor conferred a longer second stage (p = 0.02), a
      trend to more active-phase labor disorders (p = 0.06), and a greater risk of
      cesarean delivery. Overall, 12 patients (9%) underwent primary cesarean section:
      2 (6.9%) from the engaged group, 6 (6.8%) from the dipping group, and 4 (27%)
      from the floating group (p = 0.042). CONCLUSION: Most nulliparous women in this
      study presented in labor with an unengaged fetal head. Those with a floating
      fetal head demonstrated higher rates of cesarean section than those with dipping
      or engaged heads in early labor.

PMID- 9605304
TI  - Pediatric coverage of the delivery room: an analysis of manpower utilization.
AB  - OBJECTIVES: To determine the frequency and pattern of pediatric calls to the
      delivery room and the actual type of medical care administered to the newborn in
      the delivery room. STUDY DESIGN: This was a prospective observational study of
      2554 births in a university-affiliated tertiary care hospital. Existing protocols
      required the attendance of a pediatric resident or neonatal fellow at all
      deliveries other than uncomplicated vaginal term births. The pediatrician's
      activity in the delivery room was characterized as either "medical care" or
      "minimal care." Results were analyzed by diagnostic category. RESULTS:
      Pediatricians attended 646 of the deliveries (25%). Medical care was administered
      in 204 of the deliveries, representing 31% of the time they were at a delivery
      and 8% of all deliveries. The three major indications for pediatric delivery room
      attendance were cesarean sections (n = 253; 39%), presence of meconium in
      amniotic fluid (n = 117; 18%), and vacuum deliveries (n = 117; 18%). Medical care
      was required only in 1 of 56 cases of elective repeat cesarean sections, in 1 of
      20 cases of a cesarean section for nonprogress of labor, and in 1 of 38 cases
      when thin meconium was present. In contrast, medical care was needed in 52 of 81
      (64%) cases of cesarean sections for fetal distress, in 11 of 11 (100%) of the
      cesarean sections for multiple births, and in 67 of 89 (85%) cases of thick
      meconium (p < 0.05). There was a need for medical attendance after the birth in
      less than 1% of 1908 cases for which the pediatrician was not initially called to
      delivery room. CONCLUSION: Because their medical skills were needed only one of
      three times that pediatricians were called to the delivery room, and then mostly
      in specific risk situations, more selective use of pediatric manpower for
      delivery room coverage may lead to a more efficient use of medical resources
      without any apparent increase in patient morbidity.

PMID- 9605311
TI  - Special imaging casebook. Mediastinal foregut cyst.

PMID- 9605309
TI  - Pulmonary cyst caused by septic emboli in the preterm infant.
AB  - A pulmonary cyst appeared in a growing preterm infant. The presumptive diagnosis
      was septic pulmonary embolism associated with the central venous catheter. The
      infant was successfully treated with antibiotic therapy and removal of the
      central venous catheter.

PMID- 9605308
TI  - Chondrodysplasia punctata with retinal colobomas: radiographic findings.

PMID- 9605310
TI  - Umbilical cord blood gas casebook. Interpreting umbilical cord blood gases, II.

PMID- 9605313
TI  - Calculated electrostatic gradients in recombinant human H-chain ferritin.
AB  - Calculations to determine the electrostatic potential of the iron storage protein
      ferritin, using the human H-chain homopolymer (HuHF), reveal novel aspects of the
      protein. Some of the charge density correlates well with regions previously
      identified as active sites in the protein. The three-fold channels, the putative
      ferroxidase sites, and the nucleation sites all show expectedly negative values
      of the electrostatic potential. However, the outer entrance to the three-fold
      channels are surrounded by regions of positive potential, creating an
      electrostatic field directed toward the interior cavity. This electrostatic
      gradient provides a guidance mechanism for cations entering the protein cavity,
      indicating the three-fold channel as the major entrance to the protein. Pathways
      from the three-fold channels, indicated by electrostatic gradients on the inner
      surface, lead to the ferroxidase center, the nucleation center and to the
      interior entrance to the four-fold channel. Six glutamic acid residues at the
      nucleation site give rise to a region of very negative potential, surrounding a
      small positively charged center due to the presence of two conserved arginine
      residues, R63, in close proximity (4.9 A), suggesting that electrostatic fields
      could also play a role in the nucleation process. A large gradient in the
      electrostatic potential at the 4-fold channel gives rise to a field directed
      outward from the internal cavity, indicating the possibility that this channel
      functions to expel cations from inside the protein. The 4-fold channel could
      therefore provide an exit pathway for protons during mineralization, or iron
      leaving the protein cavity during de-mineralization.

PMID- 9605314
TI  - Motifs and structural fold of the cofactor binding site of human glutamate
      decarboxylase.
AB  - The pyridoxal-P binding sites of the two isoforms of human glutamate
      decarboxylase (GAD65 and GAD67) were modeled by using PROBE (a recently developed
      algorithm for multiple sequence alignment and database searching) to align the
      primary sequence of GAD with pyridoxal-P binding proteins of known structure.
      GAD's cofactor binding site is particularly interesting because GAD activity in
      the brain is controlled in part by a regulated interconversion of the apo- and
      holoenzymes. PROBE identified six motifs shared by the two GADs and four proteins
      of known structure: bacterial ornithine decarboxylase, dialkylglycine
      decarboxylase, aspartate aminotransferase, and tyrosine phenol-lyase. Five of the
      motifs corresponded to the alpha/beta elements and loops that form most of the
      conserved fold of the pyridoxal-P binding cleft of the four enzymes of known
      structure; the sixth motif corresponded to a helical element of the small domain
      that closes when the substrate binds. Eight residues that interact with pyridoxal
      P and a ninth residue that lies at the interface of the large and small domains
      were also identified. Eleven additional conserved residues were identified and
      their functions were evaluated by examining the proteins of known structure. The
      key residues that interact directly with pyridoxal-P were identical in ornithine
      decarboxylase and the two GADs, thus allowing us to make a specific structural
      prediction of the cofactor binding site of GAD. The strong conservation of the
      cofactor binding site in GAD indicates that the highly regulated transition
      between apo- and holoGAD is accomplished by modifications in this basic fold
      rather than through a novel folding pattern.

PMID- 9605315
TI  - Hinge bending within the cytokine receptor superfamily revealed by the 2.4 A
      crystal structure of the extracellular domain of rabbit tissue factor.
AB  - Tissue factor (TF), a member of the cytokine receptor superfamily, is the
      obligate cofactor of coagulation factor VIIa (FVIIa), and has a pivotal role in
      initiating the extrinsic pathway of blood coagulation through formation of the TF
      x FVIIa complex. The crystal structure of the extracellular portion of rabbit TF
      has been solved at 2.35 A resolution and refined to a crystallographic R-value of
      19.1% (free R-value, 27.7%). Like the human homologue, the extracellular portion
      consists of two fibronectin type III domains connected by a short alpha-helical
      segment. Unexpectedly, the two molecules in the crystallographic asymmetric unit
      differ in their relative domain-domain orientation, revealing unsuspected hinge
      motion consisting of a rotation of about 12.7 degrees around an axis intersecting
      the linker segment at residue 106. Superposition of rabbit tissue factor with
      free and bound human tissue factor allows for the detection of an identical,
      albeit smaller, hinge motion in human TF induced upon binding of FVIIa. This
      raises the possibility that a very similar hinge axis may be present in other
      members of the cytokine receptor superfamily.

PMID- 9605316
TI  - Crystal structures of the Klenow fragment of Thermus aquaticus DNA polymerase I
      complexed with deoxyribonucleoside triphosphates.
AB  - The crystal structures of the Klenow fragment of the Thermus aquaticus DNA
      polymerase I (Klentaq1) complexed with four deoxyribonucleoside triphosphates
      (dNTP) have been determined to 2.5 A resolution. The dNTPs bind adjacent to the O
      helix of Klentaq1. The triphosphate moieties are at nearly identical positions in
      all four complexes and are anchored by three positively charged residues, Arg659,
      Lys663, and Arg587, and by two polar residues, His639 and Gln613. The
      configuration of the base moieties in the Klentaq1/dNTP complexes demonstrates
      variability suggesting that dNTP binding is primarily determined by recognition
      and binding of the phosphate moiety. However, when superimposed on the Taq
      polymerase/blunt end DNA complex structure (Eom et al., 1996), two of the
      dNTP/Klentaq1 structures demonstrate appropriate stacking of the nucleotide base
      with the 3' end of the DNA primer strand, suggesting that at least in these two
      binary complexes, the observed dNTP conformations are functionally relevant.

PMID- 9605312
TI  - Refolding rate of stability-enhanced cytochrome c is independent of thermodynamic
      driving force.
AB  - N52I iso-2 cytochrome c is a variant of yeast iso-2 cytochrome c in which
      asparagine substitutes for isoleucine 52 in an alpha helical segment composed of
      residues 49-56. The N52I substitution results in a significant increase in both
      stability and cooperativity of equilibrium unfolding, and acts as a "global
      suppressor" of destabilizing mutations. The equilibrium m-value for denaturant
      induced unfolding of N52I iso-2 increases by 30%, a surprisingly large amount for
      a single residue substitution. The folding/unfolding kinetics for N52I iso-2 have
      been measured by stopped-flow mixing and by manual mixing, and are compared to
      the kinetics of folding/unfolding of wild-type protein, iso-2 cytochrome c. The
      results show that the observable folding rate and the guanidine hydrochloride
      dependence of the folding rate are the same for iso-2 and N52I iso-2, despite the
      greater thermodynamic stability of N52I iso-2. Thus, there is no linear free
      energy relationship between mutation-induced changes in stability and observable
      refolding rates. However, for N52I iso-2 the unfolding rate is slower and the
      guanidine hydrochloride dependence of the unfolding rate is smaller than for iso
      2. The differences in the denaturant dependence of the unfolding rates suggest
      that the N52I substitution decreases the change in the solvent accessible
      hydrophobic surface between the native state and the transition state. Two
      aspects of the results are inconsistent with a two-state folding/unfolding
      mechanism and imply the presence of folding intermediates: (1) observable
      refolding rate constants calculated from the two-state mechanism by combining
      equilibrium data and unfolding rate measurements deviate from the observed
      refolding rate constants; (2) kinetically unresolved signal changes ("burst
      phase") are observed for both N52I iso-2 and iso-2 refolding. The "burst phase"
      amplitude is larger for N52I iso-2 than for iso-2, suggesting that the
      intermediates formed during the "burst phase" are stabilized by the N52I
      substitution.

PMID- 9605318
TI  - Two "unrelated" families of ATP-dependent enzymes share extensive structural
      similarities about their cofactor binding sites.
AB  - Two proteins, D-alanine:D-alanine ligase and cAMP-dependent protein kinase, share
      a remarkable degree of structural convergence despite having different three
      dimensional folds and different enzymatic functions. Here we report that as many
      as 103 residues from 10 segments form two identical super-secondary structures
      between which the cofactor ATP is bound. The cofactor, two bound metal cations,
      and several water molecules form a large network of electrostatic and hydrophobic
      interactions common to both enzymes, and these are mediated by the similar
      placement of equivalent amino acids within the common supersecondary structures.

PMID- 9605317
TI  - The role of polar interactions in the molecular recognition of CD40L with its
      receptor CD40.
AB  - CD40 Ligand (CD40L) is transiently expressed on the surface of T-cells and binds
      to CD40, which is expressed on the surface of B-cells. This binding event leads
      to the differentiation, proliferation, and isotype switching of the B-cells. The
      physiological importance of CD40L has been demonstrated by the fact that
      expression of defective CD40L protein causes an immunodeficiency state
      characterized by high IgM and low IgG serum levels, indicating faulty T-cell
      dependent B-cell activation. To understand the structural basis for CD40L/CD40
      association, we have used a combination of molecular modeling, mutagenesis, and X
      ray crystallography. The structure of the extracellular region of CD40L was
      determined by protein crystallography, while the CD40 receptor was built using
      homology modeling based upon a novel alignment of the TNF receptor superfamily,
      and using the X-ray structure of the TNF receptor as a template. The model shows
      that the interface of the complex is composed of charged residues, with CD40L
      presenting basic side chains (K143, R203, R207), and CD40 presenting acidic side
      chains (D84, E114, E117). These residues were studied experimentally through site
      directed mutagenesis, and also theoretically using electrostatic calculations
      with the program Delphi. The mutagenesis data explored the role of the charged
      residues in both CD40L and CD40 by switching to Ala (K143A, R203A, R207A of
      CD40L, and E74A, D84A, E114A, E117A of CD40), charge reversal (K143E, R203E,
      R207E of CD40L, and D84R, E114R, E117R of CD40), mutation to a polar residue
      (K143N, R207N, R207Q of CD40L, and D84N, E117N of CD40), and for the basic side
      chains in CD40L, isosteric substitution to a hydrophobic side chain (R203M,
      R207M). All the charge-reversal mutants and the majority of the Met and Ala
      substitutions led to loss of binding, suggesting that charged interactions
      stabilize the complex. This was supported by the Delphi calculations which
      confirmed that the CD40/CD40L residue pairs E74-R203, D84-R207, and E117-R207 had
      a net stabilizing effect on the complex. However, the substitution of hydrophilic
      side chains at several of the positions was tolerated, which suggests that
      although charged interactions stabilize the complex, charge per se is not crucial
      at all positions. Finally, we compared the electrostatic surface of TNF/TNFR with
      CD40L/CD40 and have identified a set of polar interactions surrounded by a wall
      of hydrophobic residues that appear to be similar but inverted between the two
      complexes.

PMID- 9605319
TI  - A thioredoxin fusion protein of VanH, a D-lactate dehydrogenase from Enterococcus
      faecium: cloning, expression, purification, kinetic analysis, and
      crystallization.
AB  - The gene encoding the vancomycin resistance protein VanH from Enterococcus
      faecium, a D-lactate dehydrogenase, has been cloned into a thioredoxin expression
      system (pTRxFus) and expressed as a fusion protein. The use of several other
      expression systems yielded only inclusion bodies from which no functional protein
      could be recovered. Experiments to remove the thioredoxin moiety by enterokinase
      cleavage at the engineered recognition site under a variety of conditions
      resulted in nonspecific proteolysis and inactivation of the protein. The intact
      fusion protein was, therefore, used for kinetic studies and crystallization
      trials. It has been purified to greater than 90% homogeneity by ammonium sulfate
      precipitation followed by phenyl Sepharose chromatography. Based on k(cat)/KM for
      pyruvate, it is 20% as active as native VanH. Michaelis constants for NADPH,
      NADH, and pyruvate, of approximately 3.5 microM, 19.0 microM, and 1.5 mM,
      respectively, were comparable to those reported for the native VanH (Bugg TDH et
      al., 1991, Biochemistry 30:10408-10415). Like native VanH, maximum activity of
      the fusion protein requires the presence of an anion (phosphate or acetate),
      however, in addition, a strongly reducing environment is needed for optimal
      efficacy. Competitive inhibition constants for ADP-ribose, NAD+, and oxamate have
      also been determined. Crystallization by hanging drop vapor diffusion produced
      two different crystal forms, one hexagonal and the other tetragonal. Flash-frozen
      crystals of the tetragonal form diffracted to 3.0 A resolution at a synchrotron
      radiation source.

PMID- 9605320
TI  - Reactivation of thermally inactivated pre-beta-lactamase by DnaK, DnaJ, and GrpE.
AB  - To understand the role of the 23-amino acid signal sequence in the folding and
      stability of beta-lactamase, the precursor and a mutant beta-lactamase with a 19
      amino acid signal sequence deletion were synthesized in vitro using an
      Escherichia coli cell-free coupled transcription/translation system.
      Approximately 30% of the newly synthesized full-length precursor and 60% of the
      deletion mutant polypeptides were terminated and released from the ribosomes as
      active enzyme. Activity of the pre-beta-lactamase, but not the mutant, was
      unstable at 37 degrees C, suggesting that the signal sequence causes the enzyme
      to unfold. This inactivation was independent of ATP. Pre-beta-lactamase activity
      was stabilized by lowering the temperature to 30 degrees C. Furthermore, addition
      of the molecular chaperones DnaK/J and GrpE, in the presence of ATP and Mg2+,
      restored the activity of the temperature-inactivated precursor. The precursor
      formed a stable complex with DnaK and GrpE. Both ATP and DnaJ were required for
      recovery of enzymatic activity, indicating that DnaJ may bind transiently to the
      complex. These results suggest that the signal sequence of the pre-beta-lactamase
      causes a temperature-dependent unfolding of the synthesized enzyme and that
      DnaK/J and GrpE interact with unfolded pre-beta-lactamase to promote refolding of
      the protein into its native, enzymatically active conformation.

PMID- 9605321
TI  - Topology of sarcoplasmic reticulum Ca2+-ATPase: an infrared study of thermal
      denaturation and limited proteolysis.
AB  - Sarcoplasmic reticulum Ca2+-ATPase structure and organization in the membrane has
      been studied by infrared spectroscopy by decomposition of the amide I band.
      Besides the component bands assignable to secondary structure elements such as
      alpha-helix, beta-sheet, etc...., two unusual bands, one at 1,645 cm(-1) in H2O
      buffer and the other at 1,625 cm(-1) in D2O buffer are present. By perturbing the
      protein using temperature and limited proteolysis, the band at 1,645 cm(-1) is
      tentatively assigned to alpha-helical segments located in the cytoplasmic domain
      and coupled to beta-sheet structure, whereas the band at 1,625 cm(-1) arises
      probably from monomer-monomer contacts in the native oligomeric protein. The
      secondary structure obtained is 33% alpha-helical segments in the transmembrane
      plus stalk domain; 20% alpha-helix and 22% beta-sheet in the cytoplasmic domain
      plus 19% turns and 6% unordered structure. Thermal unfolding of Ca2+-ATPase is a
      complex process that cannot be described as a two-state denaturation. The results
      obtained are compatible with the idea that the protein is an oligomer at room
      temperature. The loss of the 1,625 cm(-1) band upon heating would be consistent
      with a disruption of the oligomers in a process that later gives rise to
      aggregates (appearance of the 1,618 cm(-1) band). This picture would also be
      compatible with early results suggesting that processes governing Ca2+
      accumulation and ATPase activity are uncoupled at temperatures above 37 degrees
      C, so that while ATPase activity proceeds at high rates, Ca2+ accumulation is
      inhibited.

PMID- 9605322
TI  - The observation of chaperone-ligand noncovalent complexes with electrospray
      ionization mass spectrometry.
AB  - Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) was
      applied for the study of noncovalent chaperone SecB-ligand complexes produced in
      solution and examined in the gas phase with the aid of electrospray ionization
      (ESI). Since chaperone proteins are believed to recognize and bind only with
      ligands with nonnative tertiary structure, this work required careful unfolding
      of the ligand and subsequent reaction with the intact chaperone (the noncovalent
      tetrameric protein, SecB). A high denaturant concentration was employed to
      produce nonnative structures of the OppA, and microdialysis of the resulting
      solutions containing the chaperone-ligand complexes was carried out to rapidly
      remove the denaturant prior to analysis. Multistage mass spectrometry was
      essential to the successful study of these complexes since the initial mass
      spectra indicated extensive adduction that precluded mass measurements, even
      after microdialysis. However, low energy collisional activation of the ions in
      the FTICR trap proved useful for adduct removal, and careful control of
      excitation level preserved the intact complexes of interest, revealing a 1:1
      SecB:OppA stoichiometry. To our knowledge, these results present the first direct
      observation of chaperone-ligand noncovalent complexes and the highest molecular
      weight heterogeneous noncovalent complex observed to date by mass spectrometry.
      Furthermore, these results highlight the capabilities of FTICR for the study of
      such complex systems, and the development of a greater understanding of chaperone
      interactions in protein export.

PMID- 9605323
TI  - Isolation and characterization of a DnaJ-like protein in rats: the C-terminal 10
      kDa domain of hsc70 is not essential for stimulating the ATP-hydrolytic activity
      of hsc70 by a DnaJ-like protein.
AB  - A DnaJ-like protein, RDJ1, was isolated from a rat brain cDNA library. The
      protein is predicted to have 397 amino acid residues and shares 99% identity to
      that of HDJ2, a human DnaJ-like protein. RDJ1 was also shown to rescue the
      temperature-sensitive lethality of a strain containing a mutated cytosolic DnaJ
      in yeast, ydj1-151. Fragments containing the J-domain of RDJ1 either with or
      without the G/F motif were expressed in Escherichia coli. The purified proteins
      stimulated the ATPase activity of hsc70 and of the 60-kDa N-terminal fragment of
      hsc70. These results imply that RDJ1 can interact with the N-terminal 60-kDa
      fragment of hsc70 to activate ATP hydrolysis by hsc70.

PMID- 9605324
TI  - Calorimetric analyses of the interaction between SecB and its ligands.
AB  - SecB is a chaperone in Escherichia coli dedicated to export of proteins from the
      cytoplasm to the periplasm and outer membrane. It functions to bind and deliver
      precursors of exported proteins to the translocation apparatus before they fold
      into their native structures, thus maintaining them in a competent state for
      translocation across the membrane. The natural ligands of SecB are precursor
      proteins containing leader sequences. There are numerous reports in the
      literature indicating that SecB does not specifically recognize the leader
      peptides. However, two published investigations have concluded that the leader
      peptide is the recognition element (Watanabe M, Blobel G. 1989. Cell 58:685-705;
      Watanabe M, Blobel G. 1995. Proc Natl Acad Sci USA 92:10133-10136). In this work
      we use titration calorimetry to show that SecB binds two physiological ligands,
      which contain leader sequences, with no higher affinity than the same molecules
      lacking their leader sequences. Indeed, for one ligand the presence of the leader
      sequence reduces the affinity. Therefore, it can be concluded that the leader
      sequence provides no positive contribution to the binding energy.

PMID- 9605325
TI  - What should the Z-score of native protein structures be?
AB  - The Z-score of a protein is defined as the energy separation between the native
      fold and the average of an ensemble of misfolds in the units of the standard
      deviation of the ensemble. The Z-score is often used as a way of testing the
      knowledge-based potentials for their ability to recognize the native fold from
      other alternatives. However, it is not known what range of values the Z-scores
      should have if one had a correct potential. Here, we offer an estimate of Z
      scores extracted from calorimetric measurements of proteins. The energies
      obtained from these experimental data are compared with those from computer
      simulations of a lattice model protein. It is suggested that the Z-scores
      calculated from different knowledge-based potentials are generally too small in
      comparison with the experimental values.

PMID- 9605326
TI  - The role of tyrosine 121 in cofactor binding of 5-aminolevulinate synthase.
AB  - 5-Aminolevulinate synthase (EC 2.3.1.37) is the first enzyme in the heme
      biosynthesis in nonplant eukaryotes and some prokaryotes. It functions as a
      homodimer and requires pyridoxal 5'-phosphate as an essential cofactor. Tyr-121
      is a conserved residue in all known sequences of 5-aminolevulinate synthases.
      Further, it corresponds to Tyr-70 of Escherichia coli aspartate aminotransferase,
      which has been shown to interact with the cofactor and prevent the dissociation
      of the cofactor from the enzyme. To test whether Tyr-121 is involved in cofactor
      binding in murine erythroid 5-aminolevulinate synthase, Tyr-121 of murine
      erythroid 5-aminolevulinate synthase was substituted by Phe and His using site
      directed mutagenesis. The Y121F mutant retained 36% of the wild-type activity and
      the Km value for substrate glycine increased 34-fold, while the activity of the
      Y121H mutant decreased to 5% of the wild-type activity and the Km value for
      glycine increased fivefold. The pKa1 values in the pH-activity profiles of the
      wild-type and mutant enzymes were 6.41, 6.54, and 6.65 for wild-type, Y121F, and
      Y121H, respectively. The UV-visible and CD spectra of Y121F and Y121H mutants
      were similar to those of the wild-type with the exception of an absorption
      maximum shift (420 --> 395 nm) for the Y121F mutant in the visible spectrum
      region, suggesting that the cofactor binds the Y121F mutant enzyme in a more
      unrestrained manner. Y121F and Y121H mutant enzymes also exhibited lower affinity
      than the wild-type for the cofactor, reflected in the Kd values for pyridoxal 5'
      phosphate (26.5, 6.75, and 1.78 microM for Y121F, Y121H, and the wild-type,
      respectively). Further, Y121F and Y121H proved less thermostable than the wild
      type. Taken together, these findings indicate that Tyr-121 plays a critical role
      in cofactor binding of murine erythroid 5-aminolevulinate synthase.

PMID- 9605327
TI  - Synthesis, physicochemical characterization, and crystallization of a putative
      retro-coiled coil.
AB  - An artificial HIV enhancer-binding polypeptide has recently been dimerized by
      covalently linking it to the leucine zipper motif of the yeast transcriptional
      activator GCN4 (Liu N et al., 1997, Eur Biophys J 25:399-403). Although it seemed
      that the dimerization of this peptide could be best achieved by the use of the
      retro sequence of the leucine zipper, this approach was not implemented in the
      original construct. As the first step toward the synthesis of a basic region
      retro leucine zipper HIV enhancer-binding fusion protein, we have now prepared
      the retro version of the leucine zipper (r-LZ35) and performed initial
      physicochemical characterization. Circular dichroism and sedimentation
      equilibrium studies showed that, at concentrations < 100 microM, the retro
      peptide was an unstructured monomer. At higher concentrations, however, the
      monomer was in equilibrium with a tetramer and, at 1 mM, the retro peptide was
      almost fully helical. N-terminal extension of the retro peptide by the tripeptide
      Cys-Gly-Gly resulted in a 38-residue polypeptide that could be covalently
      dimerized by forming a disulfide bond between two chains to give the peptide (r
      LZ38)2. Even in the low micromolar concentration range peptide (r-LZ38)2 formed a
      stable, noncovalent, helical dimer as revealed by circular dichroism and
      sedimentation equilibrium in the presence and absence of guanidinium chloride. (r
      LZ38)2 has been crystallized and X-ray structural analysis is under way. The
      disulfide-crosslinked retro-leucine zipper may lend itself to interesting protein
      structural studies, including protein design. The present work also highlights
      the structural and functional potential of retro proteins in general.

PMID- 9605328
TI  - Mutational analysis of the active site of indoleglycerol phosphate synthase from
      Escherichia coli.
AB  - Indoleglycerol phosphate synthase catalyzes the ring closure of 1-(2
      carboxyphenylamino)-1-deoxyribulose 5'-phosphate to indoleglycerol phosphate, the
      fifth step in the pathway of tryptophan biosynthesis from chorismate. Because
      chemical synthesis of indole derivatives from arylamino ketones requires drastic
      solvent conditions, it is interesting by what mechanism the enzyme catalyzes the
      same condensation reaction. Seven invariant polar residues in the active site of
      the enzyme from Escherichia coli have been mutated directly or randomly, to
      identify the catalytically essential ones. A strain of E. coli suitable for
      selecting and classifying active mutants by functional complementation was
      constructed by precise deletion of the trpC gene from the genome. Judged by
      growth rates of transformants on selective media, mutants with either S58 or S60
      replaced by alanine were indistinguishable from the wild-type, but R186 replaced
      by alanine was still partially active. Saturation random mutagenesis of
      individual codons showed that E53 was partially replaceable by aspartate and
      cysteine, whereas K114, E163, and N184 could not be replaced by any other
      residue. Partially active mutant proteins were purified and their steady-state
      kinetic and inhibitor binding constants determined. Their relative catalytic
      efficiencies paralleled their relative complementation efficiencies. These
      results are compatible with the location of the essential residues in the active
      site of the enzyme and support a chemically plausible catalytic mechanism. It
      involves two enzyme-bound intermediates and general acid-base catalysis by K114
      and E163 with the support of E53 and N184.

PMID- 9605329
TI  - Characterization of Escherichia coli thioredoxin variants mimicking the active
      sites of other thiol/disulfide oxidoreductases.
AB  - Thiol/disulfide oxidoreductases like thioredoxin, glutaredoxin, DsbA, or protein
      disulfide isomerase (PDI) share the thioredoxin fold and a catalytic disulfide
      bond with the sequence Cys-Xaa-Xaa-Cys (Xaa corresponds to any amino acid).
      Despite their structural similarities, the enzymes have very different redox
      properties, which is reflected by a 100,000-fold difference in the equilibrium
      constant (K(eq)) with glutathione between the most oxidizing member, DsbA, and
      the most reducing member, thioredoxin. Here we present a systematic study on a
      series of variants of thioredoxin from Escherichia coli, in which the Xaa-Xaa
      dipeptide was exchanged by that of glutaredoxin, PDI, and DsbA. Like the
      corresponding natural enzymes, all thioredoxin variants proved to be stronger
      oxidants than the wild-type, with the order wild-type < PDI-type < DsbA-type <
      glutaredoxin-type. The most oxidizing, glutaredoxin-like variant has a 420-fold
      decreased value of K(eq), corresponding to an increase in redox potential by 75
      mV. While oxidized wild-type thioredoxin is more stable than the reduced form
      (delta deltaG(ox/red) = 16.9 kJ/mol), both redox forms have almost the same
      stability in the variants. The pH-dependence of the reactivity with the
      alkylating agent iodoacetamide proved to be the best method to determine the pKa
      value of thioredoxin's nucleophilic active-site thiol (Cys32). A pKa of 7.1 was
      measured for Cys32 in the reduced wild-type. All variants showed a lowered pKa of
      Cys32, with the lowest value of 5.9 for the glutaredoxin-like variant. A
      correlation of redox potential and the Cys32 pKa value could be established on a
      quantitative level. However, the predicted correlation between the measured delta
      deltaG(ox/red) values and Cys32 pKa values was only qualitative.

PMID- 9605330
TI  - Assembly and crystallization of the complex between the human T cell coreceptor
      CD8alpha homodimer and HLA-A2.
AB  - A strategy for overexpression in Escherichia coli of the extracellular
      immunoglobulin domain of human CD8alpha was devised using codon usage alterations
      in the 5' region of the gene, designed so as to prevent the formation of
      secondary structures in the mRNA. A fragment of CD8alpha, comprising residues 1
      120 of the mature protein, excluding the signal peptide and the membrane-proximal
      stalk region, was recovered from bacterial inclusion bodies and refolded to
      produce a single species of homodimeric, soluble receptor. HLA-A2 heavy chain,
      beta2-microglobulin and a synthetic peptide antigen corresponding to the pol
      epitope from HIV-1 were also expressed in E. coli, refolded and purified.
      CD8alpha/HLA-A2 complexes were formed in solution and by co-crystallization with
      a stoichiometry of one CD8alpha alpha dimer to one HLA-A2-peptide unit.

PMID- 9605331
TI  - Homologues of 26S proteasome subunits are regulators of transcription and
      translation.
AB  - Single copies of an alpha-helical-rich motif are demonstrated to be present
      within subunits of the large multiprotein 26S proteasome and eukaryotic
      initiation factor-3 (eIF3) complexes, and within proteins involved in
      transcriptional regulation. In addition, p40 and p47 subunits of eIF3 are shown
      to be homologues of the proteasome subunit Mov34, and transcriptional regulators
      JAB1/pad1. Finally, the proteasome subunit S5a and the p44 subunit of the basal
      transcription factor IIH (TFIIH) are identified as homologues. The presence of
      homologous, and sometimes identical, proteins in contrasting functional contexts
      suggests that the large multisubunit complexes of the 26S proteasome, eIF3 and
      TFIIH perform overlapping cellular roles.

PMID- 9605334
TI  - Baseline length and automated fitting of denaturation data.
AB  - To understand relationships between protein sequence and stability, we often
      compare data from proteins that differ by the substitution of one amino acid.
      Frequently, an amino acid change causes the cooperative denaturation transitions
      to shift to lower temperatures, diminishing the signal from the native state.
      Here we show that apparent stability changes, i.e., the free energy of
      denaturation, deltaGD, can also be caused by a deficiency of points in the low
      temperature end of the transition. In addition, we suggest a method for
      overcoming this problem.

PMID- 9605332
TI  - Crystal structures of two mutants that have implications for the folding of
      bovine pancreatic ribonuclease A.
AB  - The Tyr92-Pro93 peptide group of bovine pancreatic ribonuclease A (RNase A)
      exists in the cis conformation in the native state. From unfolding/refolding
      kinetic studies of the disulfide-intact wild-type protein and of a variant in
      which Pro93 had been replaced by Ala, it had been suggested that the Tyr92-Ala93
      peptide group also exists in the cis conformation in the native state. Here, we
      report the crystal structure of the P93A variant. Although there is disorder in
      the region of residues 92 and 93, the best structural model contains a cis
      peptide at this position, lending support to the results of the kinetics
      experiments. We also report the crystal structure of the C[40, 95]A variant,
      which is an analog of the major rate-determining three-disulfide intermediate in
      the oxidative folding of RNase A, missing the 40-95 disulfide bond. As had been
      detected by NMR spectroscopy, the crystal structure of this analog shows disorder
      in the region surrounding the missing disulfide. However, the global chain fold
      of the remainder of the protein, including the disulfide bond between Cys65 and
      Cys72, appears to be unaffected by the mutation.

PMID- 9605333
TI  - Crystallization and preliminary X-ray diffraction analysis of gingipain R2 from
      Porphyromonas gingivalis in complex with H-D-Phe-Phe-Arg-chloromethylketone.
AB  - Gingipain R2 is a 50 kDa proteinase from the oral pathogenic bacterium
      Porphyromonas gingivalis. This proteinase, which displays no significant sequence
      homology to any protein previously analyzed by X-ray crystallography, has been
      crystallized using the vapor diffusion method. Two different crystal forms were
      obtained from a solution containing polyethylene glycol (MW 8,000) (space group
      P2(1)2(1)2(1)) or magnesium sulfate (space group R3) as precipitating agent.
      Complete diffraction data sets have been collected up to 2.0 and 2.9 A
      resolution, respectively. Cell dimensions are a = 51.9 A, b = 79.9 A, and c =
      99.6 A (P2(1)2(1)2(1)), and a = b = 176.6 A, and c = 143.4 A (R3). Considerations
      of the possible values of Vm accounts for the presence of one monomer per
      asymmetric unit in the case of the orthorhombic crystal form, whereas the
      rhombohedral crystal form, together with the analysis of the self-rotation
      function, could accommodate a tetramer in the asymmetric unit.

PMID- 9605335
TI  - Production, crystallization, and preliminary X-ray analysis of the human MHC
      class Ib molecule HLA-E.
AB  - HLA-E is the first human class Ib major histocompatibility complex molecule to be
      crystallized. HLA-E is highly conserved and almost nonpolymorphic, and has
      recently been shown to be the first specialized ligand for natural killer cell
      receptors. In functional studies, HLA-E is unlike the class Ia MHC molecules in
      having tightly restricted peptide binding specificity. HLA-E binds a limited set
      of almost identical leader sequence peptides derived from class Ia molecules and
      presents these at the cell surface for recognition by natural killer cell
      receptors. We now show that the extracellular region of HLA-E forms a stable
      complex with beta2 microglobulin and can be refolded around synthetic peptide.
      Crystals of this complex formed slowly over four to six months in the presence of
      ammonium sulphate. The crystals diffract to 2.85 A with space group P3(1)21 and
      unit cell dimensions a = 182.2 A, b = 182.2 A, c = 88.4 A.

PMID- 9605336
TI  - Development of AMPA-selective glutamate receptors in the auditory brainstem of
      the barn owl.
AB  - AMPA receptor specific antibodies were used to study the distribution and
      development of glutamate receptor subtypes (GluR1-4) in nucleus magnocellularis,
      angularis, laminaris, and the superior olive of the barn owl. Each nucleus in the
      adult barn owl expresses characteristic levels of AMPA receptor subtypes, and all
      are enriched in the subunits associated with rapid desensitization (GluR2 and 4).
      In the auditory hindbrain of the barn owl, the levels of expression of all AMPA
      receptors were very low at the time of hatching. In all nuclei, the level of
      GluR1 immunoreactivity was low to undetectable at all ages studied. In the
      cochlear nuclei, angularis and magnocellularis, levels of GluR2/3 and GluR4
      immunoreactivity increased over the first 2 weeks after hatching, coinciding with
      the morphological maturation of auditory nerve terminals in NM. In the nucleus
      laminaris and in the superior olive, GluR2/3 and GluR4 immunoreactivity reached
      adult-like patterns by 3 weeks after hatching. Thus, adult-like patterns of
      immunoreactivity appeared at least 1 month before the end of the sensitive period
      in all nuclei studied.

PMID- 9605337
TI  - Neuronal degeneration in the gerbil brainstem is associated with spongiform
      lesions.
AB  - Spongiform lesions arise in dendrites and glia in the brainstem of domestic
      Mongolian gerbils. Most pronounced within the cochlear nucleus (CN), this
      disorder is dynamic and progressive; the lesions increase in number, size, and
      extent with age. It has not been clear whether these spongioid lesions either
      cause or are associated with significant neural degeneration. In contrast, feral
      Mongolian gerbils (wild-trapped in Tuva) and their offspring show few spongiform
      lesions. The Tuvan gerbils provide an appropriate within-species control. We
      compared degeneration in the brainstem of domestic and Tuvan gerbils using the
      amino-cupric-silver (ACS) stain of de Olmos et al. [(1994) Neurotoxicol.
      Teratol., 16:545-561]. Positive histologic controls were provided by cerebellar
      stab wounds in domestic gerbils and by unilateral kainic acid injections into the
      CN of Tuvan gerbils. The ACS stain revealed extensive degeneration of axons,
      terminals, dendrites, and neurons in the brainstem of domestic gerbils.
      Neurodegeneration was most pronounced in the CN and was coextensive with
      spongiform lesions. Neurodegeneration was also seen in the trapezoid body,
      lateral lemniscus, and inferior colliculus, but was less pronounced than in the
      CN. The cerebellar stab wounds resulted in silver-stained Purkinje cells
      restricted to the stab wound local region. Kainic acid produced extensive
      neuronal and spongiform degeneration of the injected CN that was very similar to
      that spontaneously occurring in domestic gerbils. In contrast, the non-injected
      CN of Tuvan gerbils showed no neuronal or spongiform degeneration with the ACS
      stain. We conclude that, in domestic gerbils, the naturally occurring spongiform
      lesions of the CN and the accompanying neurodegeneration are both results of a
      common mechanism, most probably excitotoxic.

PMID- 9605338
TI  - Long-term degeneration in the cochlear nerve and cochlear nucleus of the adult
      chinchilla following acoustic overstimulation.
AB  - Adult chinchillas were exposed once to an octave-band noise, centered at 4 kHz,
      and allowed to survive for 16 days or for 1, 2, 4, and 8 months. Axonal
      degeneration was mapped in the cochlear nucleus, using the Nauta-Rasmussen silver
      method, and related to hair cell damage and to loss of myelinated nerve fibers in
      the osseous spiral lamina of the cochlea. Axonal degeneration in the dorsal
      cochlear nucleus had already reached a peak by 16 days and disappeared after 1
      month. Meanwhile, myelinated nerve fiber degeneration in the cochlea extended
      basally, followed 2 weeks to 2 months later by spread of axonal degeneration into
      the corresponding high-frequency region of the ventral cochlear nucleus. Axonal
      degeneration occurred early in the low-frequency region of the ventral cochlear
      nucleus, followed 2-4 weeks later by spread of myelinated fiber degeneration into
      more apical regions of the cochlea. New degeneration of axons in the cochlear
      nerve and in the ventral cochlear nucleus continued to occur for up to 8 months
      after stimulation. These findings imply that plastic changes in the central
      auditory pathways could play a role in the long-term effects of cochlear damage
      and acoustic overstimulation, possibly leading to a chronic neurodegenerative
      condition in the ear and in the brain.

PMID- 9605339
TI  - Differential distribution of NMDA receptor subunit mRNA in the rat cochlear
      nucleus.
AB  - The distribution and expression of mRNAs for different subunits of the N-methyl-D
      aspartate receptor (NMDAR) were examined in the cochlear nucleus (CN) of the rat
      using radioactive in situ hybridization methods. Heavy labeling for NMDAR1
      subunit mRNA was observed in all major CN neuronal types with lower labeling for
      NMDAR2A, 2B, 2C, and 2D mRNA. Silver grain counting was used to compare
      expression of different NMDAR2 subunits between six of the major CN cell types.
      Small cells of the small cell cap/shell area had the highest expression of
      NMDAR2A-C subunit mRNAs of the cell types assessed. These small cells as well as
      fusiform and corn cells of the dorsal cochlear nucleus had higher NMDAR2C than
      other NMDAR2 subunits, providing these neuron types with a distinct expression
      pattern or profile. The other three cell types assessed, spherical bushy cells,
      granule cells, and octopus cells had relatively equivalent levels of NMDAR2A-C
      subunit expressions, providing a second distinct profile. NMDAR2D mRNA had low
      expression in all six cell types assessed.

PMID- 9605340
TI  - Localization of neurotrophin-3-like immunoreactivity in the rat cochlear nucleus.
AB  - Immunohistochemistry as well as immunohistofluorescence were used to investigate
      the distribution of the neurotrophin-3 (NT3) in the adult rat cochlear nucleus.
      We found a widespread distribution of NT3 immunolabeled neurons throughout the
      three divisions of this nucleus. NT3-like immunoreactivity was clearly population
      specific, with some cell groups heavily (various small neurons and granule cells)
      or moderately (large neurons of the ventral cochlear nucleus) stained, while
      others remained negative (a major fraction of medium and large neurons of the
      dorsal cochlear nucleus). Double-labeling experiments were performed using
      antibody against the glial fibrillary acid protein, a classic marker for mature
      astrocytes. This colocalization study revealed that NT3 immunoreactivity was also
      present in a subpopulation of astrocytes, particularly in the glia limitans and
      their projections. Numerous small cells also colocalized NT3 together with the
      glial marker in the granule cell domain and in the molecular cell layer of the
      dorsal cochlear nucleus. These results suggest that NT3 may exist in widespread
      populations of adult cochlear nucleus neurons as well as in glial cells. This
      abundant distribution of NT3-like immunoreactivity implies that this neurotrophin
      may have an important role in the continued maintenance of mature cochlear
      nucleus and makes it an attractive candidate for playing a role in regulation or
      stabilization of neuronal circuits in this nucleus.

PMID- 9605341
TI  - Calcium-binding proteins and GABA reveal spatial segregation of cell types within
      the developing lateral superior olivary nucleus of the ferret.
AB  - Chemical characteristics of developing neurons in the superior olivary complex of
      the ferret were analyzed using immunohistochemical methods. The present report of
      calcium-binding proteins in the developing and adult superior olivary complex
      shows distinct distribution patterns for parvalbumin, calbindin, and calretinin
      in the lateral superior olivary nucleus (LSO) of the developing ferret that
      correspond to distribution patterns for different projection cell types and
      neurotransmitters. In the neonate, there was an initial complementary
      distribution of calcium-binding proteins between the shell and core of the body
      of the developing LSO. Parvalbumin and calbindin-immunoreactive cells were
      present in the shell, whereas calretinin-immunoreactive cells were restricted to
      the core of the LSO. Gamma amino butyric acid (GABA), but not glycine,
      immunoreactive cells were distributed similarly in the shell of the LSO in the
      neonate. There were, in addition, reciprocal medial-to-lateral gradients of
      parvalbumin and calbindin-immunoreactive cells in the LSO shell of the neonate.
      These complementary patterns in the LSO were transient, however, and by the end
      of the second postnatal week, each calcium-binding protein differed markedly in
      its cellular distribution in the superior olive, including the LSO. GABA
      immunoreactive cells also were restricted transiently to the shell of the LSO in
      neonates. The radial segregation of transient calcium-binding expression in LSO
      cells was orthogonal to the medial-to-lateral axis in the LSO and, therefore,
      parallels fibrodendritic layers and presumed isofrequency planes of the LSO. The
      early postnatal segregation of calcium-binding proteins in the isofrequency axis
      was congruent with the gradients of contralateral and ipsilateral projection cell
      types in adult LSO. It seems likely that developmental mechanisms regulate
      expression of calcium-binding protein and neurotransmitter phenotypes and that
      these mechanisms operate in development within the isofrequency axis as well as
      along the tonotopic axis of this auditory nucleus.

PMID- 9605342
TI  - Development of N-methyl-D-aspartate receptor subunit immunoreactivity in the
      neonatal gerbil cochlear nucleus.
AB  - The distribution of immunoreactivity for the ionotropic N-methyl-D-aspartate
      (NMDA) receptor subunits was mapped in the cochlear nucleus of postnatal day (P)
      7, P14, P21, and P28 gerbils. Frozen sections and serial plastic sections of
      tissue were incubated with antibodies to NMDAR1 (NR1), NMDAR2A (NR2A), NMDAR2A/B
      (NR2A/B), and NMDAR2B (NR2B). An overall diffuse stain was noted at P7 for NR1
      and NR2A/B. Staining of neuronal somata in the dorsal cochlear nucleus molecular
      layer and fusiform cell layer, the posteroventral cochlear nucleus octopus cell
      area, and the anteroventral cochlear nucleus increased from P7 to P28. Staining
      of the neuropil (the unresolved mass of processes and axons, excluding only
      neuronal somata and distinctly stained proximal dendrites) of the deep dorsal
      cochlear nucleus and posteroventral cochlear nucleus showed a steady decrease,
      while molecular layer neuropil remained moderately stained. The NR2A antibody
      produced a distinctive staining of dendrites in the dorsal cochlear nucleus deep
      and fusiform cell layers seen first at P14 with increasing dendritic lengths
      stained at P21 and P28. Giant neurons of the deep dorsal cochlear nucleus were
      the most conspicuous somata stained by the NR2A. Their stained dendrites spanned
      much of the dorsal cochlear nucleus deep and fusiform cell layers and even
      extended into the octopus cell area of the posteroventral cochlear nucleus.
      Dendritic staining was also present in caudal and rostral posteroventral cochlear
      nucleus, first distinguishable at P14 and becoming increasingly strong. The
      Chemicon polyclonal NR2B antibody produced glial staining especially prominent in
      the caudal posteroventral cochlear nucleus and the dorsal cochlear nucleus
      fusiform cell layer, most intense at P7 and subsequently decreasing, although not
      disappearing, in all areas through P28. The Molecular Probes (Eugene, OR)
      polyclonal NR2B produced a light granular staining pattern over a number of
      somata but no glial staining. Neuropil staining was not prominent with either
      NR2B antibody. Differences in changes of neonatal immunoreactivity patterns in
      different populations of cochlear nucleus neuronal somata and dendrites for NR1,
      NR2A, NR2A/B, and NR2B suggest that alterations in some receptor composition is
      occurring over the period spanning the onset of hearing.

PMID- 9605343
TI  - Afferent regulation of glycine receptor distribution in the gerbil LSO.
AB  - Synaptic activity plays an important role in many aspects ofneuronal development,
      particularly the expression of proteins. In this study, the influence of
      inhibitory and excitatory afferents on the development of glycine receptor
      density in the lateral superior olive (LSO) of Mongolian gerbils was
      investigated. Afferent activity was manipulated by removing one or both cochleas
      at postnatal day 7, prior to the onset of sound-evoked responses. Due to the
      anatomy of the LSO, these manipulations result in either excitatory denervation,
      inhibitory denervation, or both. The density of glycine receptors in the LSO was
      determined at 21 days postnatal. Glycine receptors were either labeled with
      tritiated strychnine (3H-SN) or with an antibody directed against gephyrin, a
      protein closely associated with the receptor complex. Antibody binding was used
      to quantify the differential glycine receptor density between the medial limb
      (high frequency area) and the lateral limb (low frequency area) of the LSO. 3H-SN
      was used to quantify the amount of glycine receptors in each part of the LSO in
      control and experimental animals. In addition, changes in neuron density and
      neuron cross-sectional area were quantified following cochlear ablations. In
      control animals, the amount of glycine receptors is about 2- to 3-fold higher in
      the high-frequency than in the low-frequency region. In bilaterally ablated
      animals, the same density of glycine receptors was measured in the high- and low
      frequency region. Unilateral ablations had no significant effect on glycine
      receptor distribution, either ipsi- or contralateral to the ablation. The neuron
      cross-sectional area decreased about 30% in the ipsilateral LSO of unilaterally
      ablated animals and in bilaterally ablated animals. However, alterations of soma
      density and cross-sectional area were similar in the high- and low-frequency
      projection region. These results suggest that the distribution of glycine
      receptors is only changed when excitatory and inhibitory afferents have been
      denervated.

PMID- 9605344
TI  - Immunohistochemical evaluation of cholinergic neurons in the rat superior olivary
      complex.
AB  - The cholinergic system in the rat superior olivary complex (SOC) was evaluated by
      immunohistochemistry for choline acetyltransferase (ChAT) and vesicular
      acetylcholine transporter (VAChT) and histochemistry for acetylcholinesterase
      (AChE). ChAT-positive somata were found mostly in the lateral superior olive
      (LSO) and ventral nucleus of the trapezoid body (VNTB). In the LSO, there were
      both rostral-caudal and medial-lateral gradients in concentration of ChAT
      positive somata; the highest concentration was in the middle of the rostral
      caudal extent and the most medial part. The estimated total number of ChAT
      positive neurons in the LSO was similar to previous estimates of the total number
      of lateral olivocochlear neurons. Two groups of ChAT-positive somata were found
      in the VNTB: a dorsolateral group of larger, multipolar, and more darkly labeled
      neurons and a ventromedial group of smaller, oval, and more lightly labeled
      neurons, which was about 5 times as numerous. There was a caudal-to-rostral
      increase in number of neurons in each group. VAChT immunoreactivity,
      predominantly localized in puncta, was seen in LSO, VNTB, and LNTB, and, to a
      lesser extent, in other parts of the SOC. VAChT-positive somata were also found
      in the VNTB and medial LSO. This distribution pattern of VAChT was generally
      similar to that of ChAT. AChE labeling had a similar appearance to ChAT labeling
      in the VNTB but differed in the LSO, where AChE labeling was lighter and
      associated more with neuropil than with somata.

PMID- 9605345
TI  - Cortical cholinergic dysfunction after human head injury.
AB  - Loss of cholinergic neurotransmission is implicated in memory impairment and
      cognitive dysfunction after head injury. The aim of the present study was to
      investigate presynaptic markers, particularly in relation to cholinergic
      neurotransmission in human postmortem brain from patients who died following a
      head injury and age-matched controls. Choline acetyltransferase activity and high
      affinity nicotinic receptor binding sites were assayed in the inferior temporal
      gyrus, cingulate gyrus, and superior parietal cortex of 16 head-injured patients
      and 8 controls. Synaptophysin immunoreactivity was determined in the left
      cingulate gyrus from the same patient groups. In the head-injured group, choline
      acetyltransferase activity was consistently reduced in each cortical region
      compared to control subjects. The presence of a subdural haematoma and a
      prolonged survival period after head injury tended to be associated with lower
      choline acetyltransferase activity. In contrast to the marked reduction in
      choline acetyltransferase activity, nicotine receptor binding was unchanged in
      head-injured compared to control patients. Synaptophysin immunoreactivity in the
      cingulate gyrus was reduced by approximately 30% (p < 0.05) in the head-injured
      group compared to controls. Correlation of choline acetyltransferase activity
      with synaptophysin immunoreactivity indicated there is a deficit of cholinergic
      presynaptic terminals in postmortem human brain following head injury.

PMID- 9605346
TI  - Hyperglycemia increases neurological damage and behavioral deficits from post
      traumatic secondary ischemic insults.
AB  - The effects of post-traumatic administration of glucose 2.0 g/kg was compared to
      saline infusion with and without control of brain temperature at 37 degrees C on
      behavioral and histological measures of brain injury after controlled cortical
      impact injury complicated by a secondary ischemic insult. The glucose infusion
      increased blood glucose concentration from 114 +/- 4 to 341 +/- 76 mg/dl prior to
      the secondary ischemic insult. The resulting outcome measures were significantly
      worse in the glucose infusion group than in either control group. Mortality rate
      was significantly increased by the glucose administration, from 0% to 55% (p <
      0.001). The median contusion volume was increased from 7.9 to 64.2 by glucose
      administration (p < 0.001) and the neuronal loss in the CA1 and CA3 areas of the
      hippocampus were greater in the glucose infusion group. In the animals that
      survived for the 2 weeks of behavioral studies, the duration of beam balance was
      shorter; the percent of animals that could balance on the beam for at least 60 s
      was less, the percent of animals that could perform the beam-walking task was
      less, and the length of time required to find the platform in the Morris water
      maze task was longer in the glucose infusion group. These studies demonstrate
      that the infusion of glucose after the cortical impact injury significantly
      increases the damage caused by post-traumatic ischemic insults. The adverse
      effect on neurological outcome could not be explained by the temperature effects
      of glucose infusion.

PMID- 9605347
TI  - Moderate hypothermia for 48 hours after temporary epidural brain compression
      injury in a canine outcome model.
AB  - In a previous study with this dog model, post-insult hypothermia of 31 degrees C
      for 5 h prevented secondary intraventricular pressure (IVP) rise, but during 35
      degrees C or 38 degrees C, one-half of the dogs developed delayed IVP rise to
      brain death. We hypothesized that 31 degrees C extended to 48 h would prevent
      brain herniation. Using epidural balloon inflation, we increased contralateral
      IVP to 62 mm Hg for 90 min. Controlled ventilation was to 72 h and intensive care
      to 96 h. Group 1 dogs (n = 10) were normothermic controls (37.5 degrees C). Group
      2 dogs (n = 10) were surface-cooled from 15 to 45 min of balloon inflation and
      maintained at moderate hypothermia (31 degrees C) to 48 h. Rewarming was from 48
      to 72 h. Four additional dogs of hypothermia Group 2 had to be excluded from
      analysis for pneumonia and/or bleeding diathesis. After balloon deflation, IVP
      increased to 20 mm Hg or greater at 154 +/- 215 (range 15-720) min following the
      insult in Group 1 and at 1394 +/- 1191 (range 210-3420) min in Group 2 (p =
      0.004), still during 31 degrees C but without further increase during
      hypothermia. Further IVP rise led to brain death in Group 1 in 6 of 10 dogs at 44
      +/- 18 (range 21-72) h (all during controlled ventilation); and in Group 2, in 6
      of 10 dogs at 87 +/- 11 (range 72-96) h (p = 0.001), all after rewarming, during
      spontaneous breathing. Survival to 96 h was achieved by 4 of 10 dogs in Group 1,
      and by 7 of 10 dogs in Group 2 (NS). Three of the six brain deaths in Group 2
      occurred at 96 h. The macroscopically damaged brain volume was only numerically
      smaller in Group 2. The vermis downward shift was 6.8 +/- 3.5 mm in Group 1,
      versus 4.7 +/- 2.2 mm in Group 2 (p = 0.05). In an adjunctive study, in 4
      additional normothermic dogs, hemispheric cerebral blood flow showed post-insult
      hypoperfusion bilaterally but no evidence of hyperemia preceding IVP rise to
      brain death. In conclusion, in this model, moderate hypothermia during and for 48
      h after temporary epidural brain compression can maintain a low IVP during
      hypothermia but cannot prevent lethal brain swelling after rewarming and may
      cause coagulopathy and pulmonary complications.

PMID- 9605348
TI  - Increased free radical production due to subdural hematoma in the rat: effect of
      increased inspired oxygen fraction.
AB  - Acute subdural hematoma (ASDH) complicates about 15%-20% of severe head injury
      patients and is one of the major causes for bad outcome, yet the pathomechanisms
      involved are not well understood. This study has employed a recently developed
      technique to determine whether ASDH induces free radicals in the underlying
      brain. We also studied the effect of increased inspired oxygen fraction (FiO2) on
      free radical production, both in the normal rat brain and after ASDH induction.
      Twelve male Sprague Dawley rats were studied over 5 h (2 h of FiO2 = 30%, 3 h of
      FiO2 = 100%). Hydroxyl radical production was measured with microdialysis using
      the salicylate trapping technique by quantitating the 2,3 dihydroxy benzoic acid
      (2,3 DHBA) and 2,5 dihydroxy benzoic acid (2,5 DHBA), degradation products, in
      either noninjured brain (n = 6) or after ASDH (n = 6). Both 2,3 DHBA and 2,5 DHBA
      increased significantly by 39% and 108%, respectively, after the induction of the
      SDH (p < 0.05). By increasing the FiO2 to 100%, 2 h after ASDH induction, the 2,3
      DHBA and 2,5 DHBA further increased only slightly (ns). After increasing the FiO2
      to 100% in the noninjured group, the mean level of 2,3 DHBA increased by 56% (p =
      0.06, ns). The level of 2,5 DHBA in the dialysate increased significantly by 56%
      (p < 0.05), when the FiO2 was increased to 100% ASDH results in a significant
      increase in free radical production. At the same time, prolonged increase in FiO2
      does not lead to further increase in free radical production in the injured
      brain.

PMID- 9605349
TI  - Disruption of MAP-2 immunostaining in rat hippocampus after traumatic brain
      injury.
AB  - The effects of diffuse brain injury on dendritic morphology in rat hippocampus
      and cortex were examined in this study using the recently described impact
      acceleration model of traumatic brain injury (Marmarou et al., 1994). Dendritic
      structure was visualized using immunostaining of microtubule associated protein-2
      (MAP-2). Brains were studied 24, 48, and 72 h after brain injury. Results from
      immunohistochemistry and light microscopy indicated a time-dependent disruption
      of dendritic cytoarchitecture in the CA1 subregion and in the hilus of the
      hippocampus but not in the dentate gyrus or CA3 subregion. Similar disruption was
      observed in the cortical mantle overlying the hippocampus. Although disruption of
      dendritic structure was observed at 24 h, the most severe damage was at 48 h
      after injury with evidence of at least partial recovery of MAP-2 immunostaining
      by 72 h. In the most severe damage, dendrites appeared to be fragmented,
      scattered, and unaligned, consisting of irregularly spaced and darkly stained
      swollen segments. A mixed pattern of immunostaining was observed in somata of
      hilar cells, with some appearing normal while others stained only faintly,
      appearing to have lost their typical polygonal shape. Semiquantitative rankings
      confirmed these qualitative findings. Immediate post-injury behavioral
      evaluations of injury severity were compared to the degree of disruption of MAP-2
      immunostaining. The results of this study indicate that diffuse brain injury is
      associated not only with axonal damage but also with injury to dendrites.

PMID- 9605350
TI  - Relationship between severity of spinal cord injury and abnormalities in
      neurogenic cardiovascular control in conscious rats.
AB  - Abnormal sympathetic tone after spinal cord injury (SCI) initially results in
      hypotension and is subsequently associated with autonomic dysreflexia
      characterized by paroxysmal hypertension and bradycardia in response to noxious
      or visceral stimuli. To evaluate the effect of a clinically relevant compression
      model of SCI on cardiovascular control in the early postinjury period, we
      monitored arterial pressure (AP) and heart rate under control resting conditions
      and after visceral stimulation (colon distension) in conscious rats for 1 week
      after clip compression injury of the cord at T5. Rats were randomly allocated
      into 4 groups (n = 8 each): sham-operated, 20, 35, and 50 g injuries. Only the 50
      g injury was associated with significant hypotension (73 +/- 4 mmHg) at 1 day
      post-SCI when compared to sham-injured rats (91 +/- 3 mmHg). In control rats,
      colon distention caused a transient pressor response of 16 +/- 3 mmHg and
      tachycardia. In rats with 20 g 35 g, and 50 g injuries, colon distension 1 day
      after SCI increased AP by 8 +/- 2, 15 +/- 3, and 21 +/- 1 mmHg, respectively. The
      hypertensive response correlated with injury severity (r = 0.75; p < 0.0001) and
      was associated with bradycardia. By 7 days after SCI, only rats with 50 g cord
      injuries experienced hypertension with reflex bradycardia with visceral
      stimulation. These data show that dysfunctional cardiovascular control after SCI
      is correlated with the severity of injury. Mild and moderate compressive SCI
      result in transient cardiovascular abnormalities which normalize by 1 week. In
      contrast, more severe injuries are associated with neurogenic hypotension and
      autonomic dysreflexia.

PMID- 9605351
TI  - Assessment of lower urinary tract functional deficit in rats with contusive
      spinal cord injury.
AB  - Traumatic spinal cord injury (SCI) produces lower urinary tract (LUT) dysfunction
      that has been studied in surgical transection models. Our aim was to assess LUT
      functional deficit in a clinically relevant model of incomplete SCI to
      investigate how partial preservation of supraspinal connections might affect LUT
      dysfunction. Standardized weight-drop contusion (10 g x 2.5 cm) or complete
      transection, was produced at T8 in female Sprague-Dawley rats. Behavioral tests
      were used to assess hind limb sensorimotor function at Day 1 after surgery and
      weekly thereafter. The urometric experiments were conducted on groups (n = 7) of
      uninjured rats and on injured rats during Weeks 1 and 2 after SCI (before and
      after spontaneous voiding was established) as well as Week 2 after a complete
      transection (n = 3). Under anesthesia, the bladder was continuously perfused with
      saline. Changes in bladder pressure and external urethral sphincter (EUS)
      electrical activity were monitored. The bladder was then dissected and weighed
      and both the bladder and spinal cord were fixed for pathoanatomical analyses. Our
      results indicate that several aspects of LUT dysfunction after contusive SCI were
      similar to transection, e.g., reduction of voiding efficiency (approximately 5%
      of normal value), decrease in inter-contraction interval (47%), increase in
      bladder capacity (8-fold), and weight (4.6-fold). One aspect appeared different
      from transection--partial recovery from acute bladder/sphincter dyssynergia.
      Because the coordination of bladder and EUS function is mediated by brainstem
      pathways, partial recovery of synergy after SCI was likely due to sparing of some
      relevant bulbospinal projections as was confirmed by retrograde transneuronal
      viral tracing.

PMID- 9605352
TI  - Interconnectedness of anatomy.

PMID- 9605353
TI  - Reorganization of NIH's neuroscience study sections: part of a larger integration
      plan.

PMID- 9605354
TI  - The 1997 R.R. Bensley Award: Lisa Anne Elferink, Wayne State University.

PMID- 9605355
TI  - 1997 Basmajian/Williams & Wilkins Award: Gary M. Mawe, University of Vermont.

PMID- 9605356
TI  - The Charles Judson Herrick Award: Carla B. Green, University of Virginia.

PMID- 9605357
TI  - Keith Roberts Porter: a modern Malpighi.

PMID- 9605358
TI  - The education and training of anatomy graduate students in the biomedical
      sciences in the twenty-first century.

PMID- 9605359
TI  - Receptor crosstalk: communication through cell signaling pathways.
AB  - The response of cells to extracellular stimuli is mediated in part by a number of
      intracellular signal transduction pathways. The frequent lack of a one-to-one
      correlation between receptor activation and intracellular responses, such as
      predictable nuclear transcription events, is perplexing. This lack of
      correlation, however, suggests that various signaling pathways intersect and
      crosstalk to modify and influence the biological outcome of a specific
      extracellular signal. In this review, the basic pathways and aspects of signal
      transduction are laid out, and known sites of crosstalk are discussed. A clearer
      understanding of receptor and cell signaling pathways and levels of crosstalk
      should provide insight into the paradoxes that underlie both imprecision and
      predictability in signal transduction.

PMID- 9605360
TI  - The Visible Human Dataset: the anatomical platform for human simulation.
AB  - One goal of a medical school education is to teach the anatomy of the living
      human. With the exception of some surface anatomy, the morphology education that
      goes on during a surgical procedure, and patient observation, live human anatomy
      is most often taught by simulation. Medical anatomy courses utilize cadavers to
      approximate the live human. Case-based curricula simulate a patient and present
      symptoms, signs, and history to mimic reality for the future practitioner.
      Radiology has provided images of the morphology, function, and metabolism of
      living humans but with images foreign to most novice observers. With the Visible
      Human database, computer simulation of the live human body will provide
      revolutionary transformations in anatomical education.

PMID- 9605361
TI  - Stroke: anatomy of a catastrophic event.
AB  - Subarachnoid hemorrhage (SAH) resulting from the rupture of a cerebral aneurysm
      represents one major cause of stroke. SAH may be followed by a spontaneous severe
      contraction of major cerebral arteries, a condition referred to as cerebral
      vasospasm. Vasospasm may result in brain ischemia or actual tissue death. This
      constrictive vascular state is devastating, remains largely untreatable, and is a
      major cause of morbidity and mortality in SAH patients. Approximately 30,000
      Americans are affected by this condition each year. The overall death rates are
      25%, and significant neurological complications occur in 50% of individuals who
      survive the initial bleed. This report highlights some of the important aspects
      of this vascular disease.

PMID- 9605362
TI  - Can we predict who will vomit after surgery?

PMID- 9605364
TI  - The discriminating power of a risk score for postoperative vomiting in adults
      undergoing various types of surgery.
AB  - BACKGROUND: Recently, we have demonstrated that the probability of postoperative
      vomiting (PV) following ENT surgery with inhalational anaesthetics can be
      predicted using a risk score. This score is based on gender, age, smoking status,
      history of motion sickness or postoperative nausea and vomiting and the duration
      of anaesthesia. Therefore, it is of interest whether this score is also accurate
      in predicting PV in patients undergoing different types of surgery. METHODS:
      Inpatients scheduled for bone, vascular, general or eye surgery were included in
      a prospective survey for PV over 24 h. Data of 1091 patients were analyzed, of
      which 542 were used for the validation of the previously constructed risk score
      (Score I). The data of the remaining 549 patients were used to evaluate the risk
      factors that contribute to PV in this setting and to develop a new score (Score
      II). The discriminating power of both scores to predict PV was tested in the
      validation set (n=542) and compared by calculating the area under the receiver
      operating characteristic (ROC) curves. RESULTS: The area under the ROC curve of
      Score I was 0.77 (SD 0.024). Risk factors for PV in the evaluation set were
      female gender, young age, history of motion sickness or postoperative nausea and
      vomiting and the type of surgery. The area under the curve of Score II was 0.75
      (SD 0.026) and was not significantly different from Score I (P=0.57). CONCLUSION:
      Score I was accurate in predicting PV in patients after most types of surgery
      with volatile anaesthetics, which suggests that this score might be useful for
      other centres as well.

PMID- 9605363
TI  - A risk score to predict the probability of postoperative vomiting in adults.
AB  - BACKGROUND: The aim of this study was to identify factors most relevant for
      postoperative vomiting (PV) and to develop a risk score to predict the
      probability of PV. METHODS: Adult inpatients scheduled for elective ear, nose and
      throat (ENT) surgery under general anaesthesia were offered to participate in a
      prospective study for PV over 24 h. No prophylactic antiemetics were used. The
      data of 1137 patients were randomized and split into an evaluation set (n=553)
      and a validation set (n=584). The evaluation set was subjected to logistic
      regression analysis to quantify the relative impact of anaesthetic, surgical and
      individual factors and to develop a risk score. The score was then tested by
      applying it to the validation set. The area under a receiver operation
      characteristic (ROC) curve was calculated and the predicted and actual incidences
      of patients were correlated. RESULTS: In the evaluation set, patient-related
      factors (female gender, young age, non-smoking, history of PV or motion sickness)
      and a high duration of anaesthesia were independent risk factors for PV. The
      probability of PV could be estimated from the equation: PV=1/(1+exp(-z)) where
      z=1.28 (gender)-0.029 (age)-0.74 x (smoking)+0.63 x (history of PV or motion
      sickness)+0.26 x (duration)-0.92. In the validation set this score achieved an
      area under the ROC-curve of 0.78 and the actual incidence correlated strongly
      with the predicted risks (R2=0.93, P<0.001). CONCLUSION: The data suggest that
      the probability of PV following ENT surgery under inhalational anaesthesia with
      low-dose opioids can be predicted by a score mainly based upon patient-related
      risk factors.

PMID- 9605365
TI  - Effects of esmolol on haemodynamic response to CO2 pneumoperitoneum for
      laparoscopic surgery.
AB  - BACKGROUND: Carbon dioxide (CO2) pneumoperitoneum for laparoscopic surgery
      increases arterial pressures, systemic vascular resistance and heart rate and
      decreases urine output. METHODS: In this double-blind randomized study esmolol,
      an ultrashort-acting beta1-adrenoceptor antagonist was compared with
      physiological saline (control) in 28 patients undergoing laparoscopic surgery in
      standardized 1 MAC isoflurane anaesthesia. Alfentanil infusion was used to
      prevent the increase of mean arterial pressure more than 25% from baseline.
      RESULTS: Esmolol effectively prevented the pressor response to induction and
      maintenance of CO2 pneumoperitoneum. Significantly (P<0.001) less alfentanil was
      needed in the esmolol group than in the control group. Urine output was higher
      (P<0.05) and plasma renin activity (P<0.01) and urine N-acetyl-beta-D
      glucosaminidase levels lower in the esmolol group when compared with the control
      group. CONCLUSIONS: Esmolol blunts the pressor response to induction and
      maintenance of pneumoperitoneum and may protect against renal ischaemia during
      pneumoperitoneum.

PMID- 9605366
TI  - Effects of intravenous anesthetics on bacterial elimination in human blood in
      vitro.
AB  - BACKGROUND: Since anesthetics are widely used in critically ill patients, this
      study investigates anesthetic effects on neutrophil and monocyte function
      concerning bacterial elimination in human whole blood. METHODS: The effects of
      thiopental (20 and 200 microg/ml), propofol (5 and 50 microg/ml), midazolam (0.15
      and 1.5 microg/ml) and ketamine (3 and 30 microg/ml) on elimination of
      Escherichia (E.) coli from whole blood were investigated in vitro after
      incubation for 1 h in both clinical (1) (n=10) and 10-fold higher (h) (n=11)
      concentrations. These data were compared to neutrophil and monocyte phagocytosis
      (1; n=6) and burst activity (1; n=10, h; n=11), measured by flow cytometry. To
      enable quantification of the clearance process, a defined number of 10(5) colony
      forming units of E. coli were added to the blood assays and bacterial growth was
      determined. RESULTS: All anesthetics delayed bacterial clearance from the blood
      in the 10-fold concentration (P<0.05). Thiopental (1+h) and propofol (h)
      suppressed neutrophil (59+/-3% and 38+/-6%) and monocytic (45+/-6% and 30+/-11%)
      oxidative burst (P<0.01). Phagocytosis was reduced even after propofol (1) in
      polymorphonuclear leukocytes (PMN) (34+/-9%; P<0.05) and monocytes (35+/-11%).
      Ketamine (h) prolonged bacterial elimination (P<0.01), which did correlate with
      inhibition of monocytic phagocytosis, by 26+/-14%. Midazolam application (h)
      resulted in an inhibition of PMN-respiratory burst by 19+/-6% (P<0.05) and
      impaired bacterial clearance (P<0.05). CONCLUSION: Thiopental, propofol,
      midazolam and ketamine affect E. coli clearance and neutrophil and monocyte
      oxidative burst and phagocytosis in vitro only in high concentrations, while
      thiopental inhibited monocytic burst and propofol impaired PMN phagocytosis even
      in clinically used concentrations. These data suggest that i.v. anesthetics in
      concentrations recommended for general anesthesia seem to have minor influence on
      the investigated host defense mechanisms.

PMID- 9605367
TI  - Influence of premedication with diazepam or morphine on the induction dose of
      eltanolone.
AB  - BACKGROUND: This study examined the influence of premedication with morphine or
      diazepam on the dose of eltanolone, a steroidal intravenous anaesthetic agent,
      required to induce anaesthesia. METHODS: Two hundred and sixteen patients, aged
      18 to 65 years, were randomly assigned to receive premedication with diazepam 10
      mg orally, morphine 10 mg intramuscularly, or placebo. The double-dummy technique
      was used to maintain blinding. Eltanolone 0.16-0.75 mg x kg(-1) was given
      intravenously over 20 s. At the commencement of injection patients were
      instructed to begin counting; if the patient ceased counting within 120 s and
      failed to respond to commands to continue, anaesthesia was considered to have
      been induced. The dose required to anaesthetise 50% of patients (ED50) was
      determined by logistic regression. RESULTS: The ED50 (95% confidence interval) of
      eltanolone in patients who received placebo premedication was 0.31 (0.27-0.34) mg
      x kg(-1). It was reduced slightly and nonsignificantly by premedication with
      diazepam, to 0.27 (0.24-0.30) mg x kg(-1), or morphine, to 0.26 (0.23-0.29) mg x
      kg(-1). Involuntary movement occurred in 65% of placebo premedicated patients.
      Its incidence was not significantly reduced by diazepam (57%), but was
      significantly (P<0.001) reduced by morphine (37%). Morphine premedication was,
      however, associated with a significant (P<0.01) increase in the incidence of
      apnoea (21%) compared to placebo premedicated patients (4%). CONCLUSION:
      Premedication with diazepam or morphine had little influence on the dose of
      eltanolone required to induce anaesthesia.

PMID- 9605368
TI  - Prognostic importance of automated ST-segment monitoring after coronary artery
      bypass graft surgery.
AB  - BACKGROUND: Automated ST-segment monitors are widely used in cardiac surgery
      units. The purpose of this study was to determine if cardiac morbidity and
      mortality, after CABG surgery, are predicted by ECG ST-segment changes on
      automated monitors. METHOD: One hundred patients, who underwent CABG, were
      included in this prospective study. ST-segment deviations were recorded by an
      automated ST monitor, in the ICU, for 24 h after surgery. A reversible ST
      depression of more than 0.1 mV or a ST elevation of more than 0.2 mV and for at
      least 1 min were considered as significant episodes. Adverse cardiac outcomes
      were defined as: myocardial infarction (MI), severe left ventricular failure,
      ventricular fibrillation (VF) and cardiac-related death. RESULTS: Sixty patients
      (group 1) presented significant episodes of ST deviation (6+/-5 episodes per
      patient). Forty patients (group 2) were free from ST changes. Eight patients from
      group 1 had postoperative adverse cardiac outcomes: 5 MI, 2 VF and 1 cardiac
      related death. Patients from group 2 were all free from adverse cardiac outcomes.
      Automated ST-segment analysis during the first 24 h had a positive predictive
      value of 13% and a negative predictive value of 100%. CONCLUSION: Automated ST
      analysis is a non-invasive, sensitive and very easy-to-use monitoring system to
      screen patients who may develop myocardial ischemia and cardiac complications
      after CABG surgery.

PMID- 9605369
TI  - The effects of nitric oxide inhalation on respiratory mechanics and gas exchange
      during endotoxaemia in the pig.
AB  - BACKGROUND: In the adult respiratory distress syndrome, nitric oxide (NO)
      inhalation improves oxygenation through reducing ventilation-perfusion
      mismatching, but detailed information on the pulmonary effects of NO inhalation
      in septic shock is scarce. The present study investigated the effects of inhaled
      NO on alveolar dead space (Vdalv) and venous admixture as well as on respiratory
      system compliance (Crs) and respiratory system resistance (Rrs) in a porcine
      model of septic shock. Protective effects of NO are discussed. METHODS: Thirteen
      anaesthetised and ventilated pigs were given an infusion of endotoxin for an
      observation time of 220 min to induce acute lung injury (ALI). In the NO-early
      group (n=6), an inhalation of 60 ppm NO was started simultaneously with the
      endotoxin infusion and continued for 190 min. In 7 control/NO-late animals, 60
      ppm NO was administered for 30 min following 190 min of endotoxin infusion.
      Haemodynamics, single-breath CO2-, pressure-, and flow signals were recorded.
      RESULTS: Endotoxin induced haemoconcentration, pulmonary vasoconstriction, and a
      decrease in Crs, while venous admixture, Vdalv, and Rrs increased. In the NO
      early group, the pulmonary vasoconstriction was attenuated, no increase in
      pulmonary venous admixture or in Vdalv was seen before cessation of NO, and the
      improvements in oxygenation outlasted the NO inhalation. In the control/NO-late
      group, the NO inhalation reversed the changes in dead space and venous admixture.
      NO had no effect on the changes in respiratory mechanics. CONCLUSION: In porcine
      ALI, 60 ppm NO diminishes pulmonary vasoconstriction and improves gas exchange by
      reducing pulmonary venous admixture and alveolar dead space, but does not prevent
      a fall in Crs. NO inhalation may help prevent long-lasting pulmonary failure.

PMID- 9605370
TI  - Percutaneous dilatational tracheostomy versus conventional surgical tracheostomy.
      A clinical randomised study.
AB  - BACKGROUND: As no clinical randomised studies have previously been performed
      comparing complications with the Ciaglia Percutaneous Dilatational Tracheostomy
      Introducer Set (PDT) and conventional surgical tracheostomy (TR), we designed a
      study with the aim of comparing the efficacy and safety of the two techniques.
      METHODS: Sixty patients selected for elective tracheostomy were randomised for
      either PDT (30 patients) or TR (30 patients). All patients had general
      anaesthesia and were ventilated with 100% oxygen. Furthermore, lidocaine with
      epinephrine 1% (3-5 ml) was used for local analgesia and to minimise bleeding
      during the procedure. RESULTS: The median time for insertion of the tracheostomy
      tube was 11.5 min (range 7-24 min) in the PDT group and 15 min (range 5-47 min)
      in the TR group (P<0.01). Complications during the procedure were cuff puncture
      of the endotracheal tube in 5 cases in the PDT group. Minor bleeding was
      encountered in 6 cases in the PDT group as opposed to 24 cases in the TR group
      (P<0.01), major bleeding in none versus 2 cases, respectively. In 8 cases in the
      PDT group, increased resistance to insertion of the tracheostomy tube was met by
      further dilatation. During the post-tracheostomy period, complications occurred
      with minor bleeding in 2 cases in the PDT group as opposed to 9 cases in the TR
      group (P<0.05), and major bleeding was encountered in 1 case in each group. Minor
      infections were encountered in 3 cases in the PDT group as opposed to 11 cases in
      the TR group (P<0.01). Major infection was encountered in none versus 8 cases,
      respectively (P<0.01). CONCLUSION: Our results indicate that the percutaneous
      dilatational tracheostomy technique performed with the Ciaglia Introducer Set is
      effective, safe and superior to conventional surgical tracheostomy as immediate
      complications as well as complications with the tracheostomy tube in situ are
      fewer and of less severity.

PMID- 9605371
TI  - Increased platelet microvesicle formation is associated with mortality in a
      porcine model of endotoxemia.
AB  - BACKGROUND: Gram-negative sepsis in humans and endotoxemia in pigs induce the
      formation of platelet microvesicles. These microvesicles are active in
      homeostasis and may thus contribute to the outcome in patients with activated
      coagulation and fibrinolysis. We decided to prospectively evaluate the effects of
      endotoxemia on microvesicle formation and some common physiologic variables
      against survival in a porcine model. METHODS: Nineteen included pigs were
      anesthetized, monitored and subjected to an infusion of E. coli endotoxin.
      Microvesicle formation was determined by flow cytometry. RESULTS: The formation
      of microvesicles was significantly increased in the 6 pigs that died during
      endotoxin exposure. This increased formation became significant from the 3rd hour
      of endotoxemia. Microvesicle formation did not increase in surviving endotoxemic
      pigs. Cardiac index, mean arterial blood pressure, base excess and systemic
      vascular resistance index were distinctly reduced in the animals that died as
      compared to those surviving the endotoxemic period. CONCLUSION: The increased
      formation of platelet microvesicles seems to be associated with poor prognosis in
      porcine endotoxemia. Since microvesicles are active in coagulation, they may
      contribute to the derangement of the coagulation system caused by endotoxemia.
      Different degrees of microvesicle formation may reflect inter-individual
      responses to a given challenge.

PMID- 9605372
TI  - The inflammatory cytokine response after autotransfusion of shed mediastinal
      blood.
AB  - BACKGROUND: The inflammatory response in patients undergoing cardiac surgery with
      cardiopulmonary bypass is well known and increased levels of inflammatory
      cytokines have been shown. High levels of cytokines have been reported in blood
      drained from the surgical field. The present study aimed to elucidate whether
      autotransfusion of shed mediastinal blood in itself causes increased cytokine
      levels in coronary artery bypass graft (CABG) patients. METHODS: A prospective,
      randomized controlled study was performed in 23 patients having elective
      uncomplicated CABG. Autotransfusion of shed mediastinal blood was done every hour
      for 18 h in group I. In group II, the shed mediastinal blood was accumulated for
      4 h in the cardiotomy reservoir and then autotransfused every hour for the next
      14 h. Plasma levels of tumour necrosis factor-alpha (TNFalpha) and interleukin
      (IL)-1alpha, IL-1beta, IL-6 were measured. In vitro study of cytokine production
      was performed with or without stimulation (phytohaemagglutinin (PHA) and
      Escherichia coli (E. coli) lipopolysaccharide (LPS)). RESULTS: We found high
      levels of IL-6 in the shed mediastinal blood. However, autotransfusion of shed
      mediastinal blood did not lead to increased level of cytokines (TNFalpha, IL
      1alpha, IL-1beta and IL-6) in plasma in group I nor in group II. In vitro study
      showed activation of the leucocytes in the shed mediastinal blood with a
      significantly increased production of TNFalpha and IL-6 both in the stimulated
      and non-stimulated samples. CONCLUSION: Shed mediastinal blood contains high
      levels of IL-6. However, autotransfusion of shed mediastinal does not cause
      measurable elevations in plasma levels of IL-6. In vitro study shows that
      autotransfusion activates leucocytes, which may enhance production of
      inflammatory cytokines.

PMID- 9605373
TI  - Dose-dependent suppression of the neutrophil respiratory burst by lidocaine.
AB  - BACKGROUND: Oxygen radical production is thought to be fundamental to the
      pathogenesis of post-ischaemic reperfusion injury which is routinely managed with
      lidocaine. Attention has, therefore, focused on the suppression of the neutrophil
      respiratory burst with a therapeutic endpoint. The widest application of
      lidocaine remains in local analgesia. METHODS: A standard chemiluminescence
      technique was used to assess the human neutrophil leukocyte response to
      increasing doses of lidocaine in the presence or absence of particulate
      hydroxyapatite. RESULTS: No reduction of oxygen radical production was seen at
      the drug concentration of 1 mg/ml. A clear, concentration-dependent inhibition
      was seen at 2 mg/ml, 3 mg/ml, 4 mg/ml and 8 mg/ml concentrations. These drug
      concentrations may be reached at or near the site of injection in local
      anaesthetic use. CONCLUSION: Lidocaine showed profound anti-inflammatory action
      in this experimental system. Controlled studies in the clinical setting would
      identify the optimal analgesic and anti-inflammatory dosage, whilst preserving
      host defence without compromising tissue repair.

PMID- 9605374
TI  - Comparison of transarterial and multiple nerve stimulation techniques for an
      initial axillary block by 45 mL of mepivacaine 1% with adrenaline.
AB  - BACKGROUND: The single-injection axillary block is rapidly performed but gives
      unpredictable results. Axillary block by multiple nerve stimulation technique
      (MNS) gives better results, but takes longer to perform. Transarterial (TA)
      injections of high doses of local anaesthetics are very successful. This double
      blind study compared both block effectiveness and anaesthesiologic time
      consumption in 100 patients, having an axillary block by either TA or MNS
      techniques. METHODS: 45 mL of 1% mepivacaine with adrenaline 5 microg/mL was used
      in each patient. Five mL was injected subcutaneously. In the TA group, 20 mL was
      injected deep to, and 20 mL superficial to the axillary artery. In the MNS group,
      four terminal motor nerves were electrolocated in the axilla, and injected with
      10 mL each. Analgesia was assessed every 10 min and when needed supplemented
      after 30 min. The block was considered successful when analgesia was present in
      all sensory nerve areas distal to the elbow. RESULTS: MNS group required 10+/-2
      min (mean+/-1 SD) for the initial block performance compared with 7+/-2 min for
      TA group, P<0.001. Latency of the initial block was shorter and the frequency of
      supplemental analgesia lower in the MNS group (mean 17 min and 12%), than in the
      TA group (25 min and 38%, respectively), P<0.001. All incomplete blocks were
      successfully supplemented by electrolocating the unblocked nerves. However, the
      total time to obtain 100% success rate was shorter in the MNS group (30 min),
      than in the TA group (38 min), P<0.001. The adverse effects (accidental
      intravascular injections and axillary haematomas) were fewer in the MNS group.
      CONCLUSION: In the hands of anaesthetists experienced in nerve electrolocation,
      the MNS technique of an initial axillary block by four separate injections of 10
      mL of mepivacaine produces faster and more extensive block than the TA technique
      by two separate injections of 20 mL. Hence, the MNS technique requires fewer
      supplementary blocks and results in faster patient readiness for surgery than the
      TA technique.

PMID- 9605375
TI  - Comparison of analgesic efficacy of oxycodone and morphine in postoperative
      intravenous patient-controlled analgesia.
AB  - BACKGROUND: Morphine has been the standard opioid in patient-controlled analgesia
      (PCA). Oxycodone, the analgesic potency of which in i.v. administration has been
      suggested to be slightly greater than that of morphine, has not yet been studied
      for its efficacy in PCA. METHODS: Fifty patients, undergoing a plastic
      reconstruction of the breast or a major operation of the vertebrae, such as
      lumbar spinal fusion, used PCA for postoperative pain. Patients were randomized
      to receive either morphine 45 microg/kg or oxycodone 30 microg/kg as i.v. bolus
      doses. Patients were assessed for pain with a visual analogue scale (VAS) and
      side effects at 3, 9 and 24 h. Venous blood samples for the measurement of plasma
      concentration of oxycodone and that of morphine and its metabolites were taken.
      RESULTS: In this study patients needed, on average, the same amount of oxycodone
      and morphine in the recovery room and on the ward. There was no difference in the
      quality of analgesia (VAS) or incidence of side effects, such as nausea,
      vomiting, pruritus and urinary retention. The plasma concentrations of morphine-6
      glucuronide showed that this metabolite might contribute to the analgesia
      resulting from morphine administration. CONCLUSIONS: The same dose of intravenous
      oxycodone and morphine administered by PCA pump was needed for immediate
      postoperative analgesia. The two drugs appear to be equipotent.

PMID- 9605376
TI  - Neurolytic thoracic paravertebral block in cancer pain. A clinical report.
AB  - BACKGROUND: Paravertebral block has successfully been used in the treatment of
      acute and chronic pain. The duration of paravertebral block could theoretically
      be prolonged by using neurolytic agents. METHODS: We retrospectively analyzed the
      results of neurolytic paravertebral blocks performed in 7 patients suffering from
      intense cancer-related thoracic pain. Thirty-seven spinal nerve roots were
      blocked during 20 visits. Nerve roots were identified by eliciting paresthesia
      radiating to the painful area. Each root was blocked separately. After test block
      using 0.5% bupivacaine, the paravertebral blocks were performed with 1-4 ml of 7%
      phenol in aqua. RESULTS: No technical failures or complications were recorded in
      the patient files. Pain relief lasted over 2 months after 4 visits (20%), from 1
      week to 1 month after 5 visits (25%), and less than 1 week after a single visit
      (5%). After 9 visits (45%), the results were poor with no significant pain
      relief. CONCLUSION: Neurolytic paravertebral block with phenol doses used in our
      patients appears to have only limited use. Some patients with pain restricted to
      a small number of thoracic segments may benefit from its use. Because of
      complication risks, this technique should be limited to intractable pain in
      cancer patients with poor prognosis.

PMID- 9605377
TI  - Near fatal intoxication with controlled-release morphine tablets in a depressed
      woman.
AB  - BACKGROUND: A 46-year-old woman suffering from a reactive depression was admitted
      to the emergency room in coma and with severe respiratory failure. She later
      developed cardiovascular instability and general convulsions. Two days following
      admission the patient had no respiratory effort but was able to communicate in
      writing that she had ingested a large amount of controlled-release morphine
      tablets. Following treatment with naloxone she was successfully weaned from the
      respirator the next day. METHODS: Sampling for determination of plasma and urine
      concentrations of morphine and its metabolites morphine-3-glucuronide (M3G) and
      morphine-6-glucuronide (M6G) was started 60 h after the presumed time of intake
      and continued up to 8 days after admission. RESULTS: The initial plasma
      concentrations of morphine, M3G and M6G were 2160, 13100 and 2330 nM,
      respectively, compatible with a lethal dose in an opioid-naive patient. The
      urinary recovery of morphine, M3G and M6G corresponded to 6.8 mmol, equivalent to
      an oral intake of at least 2500 mg. CONCLUSION: The plasma concentrations of
      morphine and morphine metabolites documented in this case, indicative of
      considerable absorption of drug, demonstrate that prolonged observation is
      necessary following intoxications with controlled-release morphine tablets. This
      case also highlights the importance of continuous follow-up of oral morphine
      therapy, so that unused drug is not left unaccounted for in the patient's home.

PMID- 9605378
TI  - Effect of an endotoxin-removing column containing immobilized polymyxin B fiber
      in a patient with septic shock from gram-positive infection.
AB  - A 67-yr-old patient with septic shock caused by gram-positive infection fell into
      circulatory collapse. Direct hemoperfusion with an endotoxin-removing column was
      then carried out for 120 min. As a result, blood pressure and systemic vascular
      resistance increased significantly during this therapy. Cardiac output changed
      from hyperdynamic to normodynamic, and plasma endotoxin level decreased. After
      this treatment, the patient recovered. From this experience, we consider that the
      endotoxin-removing column may be effective for septic shock patients.

PMID- 9605379
TI  - Methemoglobinemia induced by methylene blue pertubation during laparoscopy.
AB  - Methylene blue is used to check tubal patency during laparoscopy. A case of
      methemoglobinemia which was induced by methylene blue is presented.
      Methemoglobinemia is usually treated with methylene blue; however, in patients
      with glucose-6-phosphate dehydrogenase deficiency, methylene blue can induce
      methemoglobinemia.

PMID- 9605380
TI  - Hemodynamic response to infra-renal aortic cross-clamping.

PMID- 9605381
TI  - Is epidural morphine and bupivacaine safe on surgical wards?

PMID- 9605382
TI  - Differential development of early hypertension in heterozygous transgenic
      TGR(mREN2)27 rats.
AB  - The aim of the study was to determine blood pressures in young heterozygous
      transgenic rats harbouring the Ren-2 mouse gene, TGR(mREN2)27, and to examine the
      association between blood pressure and plasma renin-angiotensin parameters during
      the conscious state. Two litters of heterozygous TGR(mREN2)27 rats and their
      normotensive Sprague-Dawley reference animals were bred in our laboratory.
      Cardiovascular phenotypes and blood, for the evaluation of plasma renin
      angiotensin-system parameters, were obtained via arterial catheters in conscious
      rats 4 weeks after birth. Blood pressure values showed a high degree of
      interindividual variability and significant litter differences in the group of
      transgenic animals ranging from normotensive tohypertensive values. Plasma
      prorenin levels were markedly increased in TGR(mREN2)27, whereas both active
      renin and angiotensin II plasma concentrations were reduced independently from
      hypertension. Plasma prorenin levels in litter 2 of transgenic animals which
      exhibited significantly elevated blood pressures were significantly higher as
      compared to those of litter 1 which showed blood pressures that were not
      significantly different from SD. These data demonstrate that the development of
      hypertension in heterozygous TGR(mREN2)27 takes place in the fourth week of
      postnatal life and exhibits large interindividual variability. Moreover,
      development of early hypertension in young heterozygous TGR(mREN2)27 is
      associated with higher plasma prorenin levels.

PMID- 9605383
TI  - Ambulatory systolic blood pressure is related to the deletion allele of the
      angiotensin I converting enzyme gene in young normotensives with parental history
      of hypertension.
AB  - The aim of the present study was to evaluate the relationship between the
      angiotensin I converting enzyme (ACE) gene polymorphism and ambulatory blood
      pressure in young normotensive males with (n=45) and without (n=100) family
      history of hypertension. Twenty-four hour and daytime systolic blood pressure was
      significantly higher in subjects with a parental history of hypertension.
      Ambulatory blood pressure values did not differ significantly across ACE
      genotypes in subjects with negative family history of hypertension. In subjects
      with a parental history of hypertension, there was a significant positive
      association between the D allele of the ACE gene polymorphism and 24-h, daytime
      and nighttime systolic blood pressure. For twenty-four hour systolic blood
      pressure there was an average 9 mmHg difference between subjects with DD and II
      genotypes. The results indicate that in normotensive subjects with a genetic
      predisposition to hypertension, ambulatory systolic blood pressure is related to
      the D allele of the ACE gene.

PMID- 9605384
TI  - Renal protective effects of efonidipine in partially nephrectomized spontaneously
      hypertensive rats.
AB  - We investigated the effects of a calcium antagonist, efonidipine, which was
      reported to dilate not only afferent arterioles but also efferent alterioles, on
      progression of renal failure in salt-loaded partially nephrectomized
      spontaneously hypertensive rats (SHR). Forty-four SHR's with 5 of 6 nephrectomy
      were divided into four groups: group 1 as control (n=20); group 2, efonidipine
      treated (n=8); group 3, enalapril-treated (n=8); and group 4, nifedipine-treated
      (n=8). The rats were given these drugs and a high-salt diet (5% NaCl) for 8
      weeks. During the experiment, systolic blood pressure (SBP) and daily urinary
      protein excretion were measured every 2 weeks. At the end of the study, serum
      creatinine was determined, and renal tissues were obtained for light microscopic
      examination. SBP was markedly reduced by 8-week antihypertensive treatment.
      (control, 267+/-7 mmHg; efonidipine, 181+/-7 mmHg; enalapril, 200+/-12 mmHg;
      nifedipine, 184+/-6 mmHg). Glomerular sclerosis developed markedly in the control
      group, but was partially prevented in all treated groups. Similarly, urinary
      protein excretion (UPE) was suppressed by efonidipine (180+/-16 mg/day) and
      enalapril (186+/-16 mg/day vs. 301+/-28 mg/day for control). In contrast,
      nifedipine failed to prevent the increase in urinary protein excretion (258+/-22
      mg/day). In conclusion, efonidipine attenuates SBP increase and ameliorates
      glomerular injury as well as nifedipine and enalapril. Furthermore, beneficial
      effects of efonidipine, but not nifedipine, on proteinuria suggest that different
      mechanisms mediate the improvement of proteinuria; one possible mechanism could
      be efferent arteriolar dilation, not reported in nifedipine.

PMID- 9605385
TI  - Circulating plasma prekallikrein and tissue kallikrein in normotensive and
      hypertensive humans: effects of angiotensin II infusion.
AB  - Kinins lower blood pressure but the stimuli leading to kinin generation and their
      origin are less well known. We administered angiotensin II in graded infusion
      doses to patients with primary hypertension and normotensive controls to study
      the effects of on circulating kallikreins. Angiotensin II infusion did not
      significantly alter plasma prekallikrein or tissue kallikrein levels and the
      plasma levels and their changes did not correlate with blood pressure levels or
      changes. In the normotensive group prekallikrein levels and renin activity
      correlated negatively with urinary sodium and chloride excretion during basal
      conditions and partially during the infusion. U-tissue kallikrein concentration
      increased in the normotensive group. Thus, acute elevation of blood pressure
      induced by angiotensin II does not activate the circulating kallikrein-kinin
      systems. Data rather indicate that the circulating kallikrein-kinin systems may
      be related to alterations in volume and sodium balance and that these mechanisms
      may be altered in primary hypertension.

PMID- 9605386
TI  - Effects of adenosine deaminase inhibition on blood pressure in old spontaneously
      hypertensive rats.
AB  - Adenosine is an ubiquitously occurring endogenous nucleoside that via cell
      surface receptors exerts multiple antihypertensive actions, and mediates a number
      of biological responses that may reduce cardiovascular disease risk. Therefore
      modulation of endogenous levels of adenosine may offer beneficial effects in
      hypertension. The objective of this study was to determine whether inhibition of
      adenosine deaminase lowers blood pressure in spontaneously hypertensive rats
      (SHR). We investigated the effects of erythro-9-(2-hydroxyl-3-nonyl) adenine
      (EHNA), an adenosine deaminase inhibitor, on hemodynamic and renal parameters in
      16-week-old and 36-week-old SHR and normotensive Wistar Kyoto rats (WKY) and in
      36-week-old SHR and WKY pretreated with 1,3-dipropyl-8-p-sulfopheznylxanthine
      (DPSPX, an adenosine antagonist that does not enter the brain and is restricted
      to the extracellular space). Adenosine deaminase inhibition with EHNA (10 mg/kg,
      iv.) produced a marked fall in arterial blood pressure in older (MABP 162.0+/-7.6
      mmHg and 120.7+/-11.7 mmHg for baseline and EHNA period, respectively; p<0.01),
      but not younger, SHR, whereas no effects on blood pressure were observed in age
      matched normotensive WKY rats. EHNA did not affect renal hemodynamic and
      excretory function in any of six groups of animals. DPSPX blocked the
      antihypertensive effects of EHNA, suggesting that the effects of EHNA on blood
      pressure are mediated via peripheral adenosine receptors. Further studies are
      required to elucidate why inhibition of adenosine deaminase lowers blood pressure
      only in older SHR. The present data suggest that inhibition of adenosine
      deaminase may provide beneficial effects in older hypertensives and lead us to
      propose that design and use of extracellular adenosine deaminase inhibitors may
      offer cardiovascular protection in hypertension.

PMID- 9605387
TI  - Mitochondrial energy metabolism in the left ventricular tissue of spontaneously
      hypertensive rats: abnormalities in both adeninenucleotide and phosphate
      translocators and enzyme adenylate-kinase and creatine-phosphokinase activities.
AB  - The aim of this study was to investigate the oxidative phosphorylation and
      additional adenosinetriphosphate (ATP) production mechanisms in mitochondria
      isolated from hypertrophied left ventricles of spontaneously hypertensive rats
      (SHR). Measurements of adenosinediphosphate (ADP)/ ATP and inorganic phosphate
      (Pi) carrier activities showed a significant reduction of Vmax values thus
      suggesting a general decrease of ATP supply in the hypertrophied ventricles.
      Investigation of mitochondrial enzyme activities showed 45% and 90% increases of
      adenylate-kinase and 80% and 110% increases of creatine-phosphokinase in 5- and
      24-week-old SHR, before and after the development of the hypertensive state,
      respectively. The abnormalities found in SHR at the mitochondrial level suggest a
      profound rearrangement of energy production mechanisms in this model of left
      ventricular hypertrophy; whether the defects are determined genetically, and then
      worsen with the hypertensive state, remains to be determined.

PMID- 9605388
TI  - Regulation of gene expression by neurotransmitters in the central nervous system.

PMID- 9605389
TI  - Slowly progressive pure word deafness.
AB  - Among the reports of primary progressive aphasia, there are few about patients
      who exhibited progressive pure word deafness with detailed auditory and
      radiological examination as well as neuropsychological assessment. We describe a
      67-year-old right-handed man who exhibited slowly progressive pure word deafness
      over a period of 9 years without exhibiting any other cognitive or mental
      deterioration. Magnetic resonance imaging of his brain revealed generalized
      cortical atrophy, particularly in the left superior temporal region. Auditory
      examination revealed severe disability in discriminating each syllable or mora of
      Japanese words despite adequate auditory acuity. He also showed impairment in
      temporal auditory discrimination assessed by the click fusion test and the click
      counting test. His ability to discriminate meaningful environmental sounds was
      mildly impaired. We discuss the pathophysiology of slowly progressive pure word
      deafness over a period of many years which was not complicated by other language
      or cognitive dysfunctions.

PMID- 9605390
TI  - Muscle pathology in the early stage of Guillain-Barre syndrome.
AB  - Although many studies have been performed on nervous tissue pathology in Guillain
      Barre syndrome (GBS), much less is known about pathological changes in skeletal
      muscle in this disorder. We have studied muscle biopsies from 5 patients with
      GBS, 5 patients with amyotrophic lateral sclerosis (control A), and 5 patients
      with polyarteritis nodosa (control B). We also examined muscle obtained after
      death from 7 patients without neurologic or muscular diseases (control C). By
      light microscopy, all specimens from patients with GBS exhibited necrosis and/or
      phagocytosis, none of which was observed in the other three controls. Neither
      small angulated fibers nor small group atrophy was found in patients with GBS and
      in control C, by contrast with controls A and B. Ultrastructurally, filamentous
      bodies, subsarcolemmal aggregates of mitochondria, accumulation of glycogen
      particles, and concentric laminated bodies were present much more frequently in
      patients with GBS than in all controls. Only GBS patients showed cytoplasmic
      bodies. These observation suggests that there is muscle involvement in the early
      stage of GBS and that these muscle changes may have an intimate and important
      relationship to the pathogenesis of GBS.

PMID- 9605391
TI  - Mitochondrial DNA analysis in ocular myopathy. Observations in 29 Portuguese
      patients.
AB  - We analyzed 29 patients with progressive external ophthalmoparesis (PEO) either
      alone or as part of a multisystem disorder. Ragged-red fibers were very abundant
      (10-20%) in 15 patients, and many of them were also cytochrome c oxidase
      negative. Biochemical analysis of the respiratory chain showed partial defects of
      single or multiple complexes in 18 patients (64%). Eleven PEO patients (38%)
      harbored single large-scale mtDNA deletions in muscle, which averaged 5.4 kb in
      size and 47% in relative abundance. One PEO patient harbored the A3243G mutation
      (MELAS mutation) in muscle (63%). Our findings, the first reported in Portuguese
      patients, confirm that single large-scale mtDNA deletions are a significant cause
      of PEO. Although ophthalmoparesis was the main clinical feature in the majority
      of patients, the clinical spectrum is broad, ranging from severe encephalopathy
      of childhood to a milder, though disabling, muscle weakness in adults.

PMID- 9605392
TI  - Analysis of creatine kinase activity in 504 patients with proximal spinal
      muscular atrophy types I-III from the point of view of progression and severity.
AB  - Mild to moderately elevated creatine kinase (CK) activity is a frequent
      biochemical finding in proximal spinal muscular atrophy (SMA). In a collaborative
      study on all types of childhood and juvenile onset SMA, we analysed the CK
      activity of 504 SMA patients (138 type I, 127 type II, 144 type IIIa, and 95 type
      IIIb patients). Under the assumption of a lognormal distribution of CK activity
      as the most appropriate statistical model, CK levels were transformed into
      logarithms and compared by standard deviation scores = CK-SDS (log). CK activity
      was statistically different between early and later onset SMA: in SMA I and II,
      about one-third of patients showed CK-SDS (log) >2 SD, the analysis of the means
      did not show significant differences. In SMA III, CK-SDS (log) was significantly
      higher (p < 0.01) than in the two other groups, which was most pronounced in SMA
      IIIb. More than 90% of SMA IIIb patients showed CK-SDS (log) values >2 vs. 57% in
      SMA IIIa. As similar values were obtained for a subgroup of 100 patients in whom
      the diagnosis of autosomal recessive SMA was confirmed by a deletion of the
      telomeric copy of the survival motor neuron gene, our results can be considered
      representative for SMA I-III. There was no correlation between CK level and
      disease duration. The fact that patients were ambulatory or chair-bound had no
      influence on CK activity in type III SMA. There was no sex influence in SMA I, II
      and IIIa. The observed higher male values in the group SMA IIIb are most likely
      the result of a lack of female patients with onset after puberty.

PMID- 9605393
TI  - Herpes simplex virus myelitis: clinical manifestations and diagnosis by the
      polymerase chain reaction method.
AB  - Herpes simplex virus (HSV) myelitis has previously been reported to be a form of
      acute ascending necrotizing myelitis caused by HSV type 2 (HSV-2). We studied
      neurological symptoms, clinical course, magnetic resonance imaging (MRI)
      findings, and diagnosis by polymerase chain reaction (PCR) methods in 9 patients
      with HSV myelitis. In 6 cases, disease onset was marked by sensorimotor
      disturbances of lower extremities and urinary disturbances, with the transverse
      myelopathy gradually ascending to the cervicothoracic spinal cord level. The
      other 3 cases showed transverse myelopathy without an ascending pattern. Six
      cases showed acute progression, while 3 cases showed a subacute course. There
      were 2 cases with recurrent episodes. Three patients recovered, however, in the
      remaining 6 patients severe sequelae such as paraplegia persisted despite
      antiviral therapy. MRI showed a hyperintense lesion on T2-weighted images.
      Gadolinium enhancement was observed in 2 cases, and 1 case showed a hyperintense
      lesion both on T1- and on T2-weighted images, suggesting hemorrhagic necrosis.
      HSV-2 was detected by PCR techniques in all 6 cases with an ascending pattern.
      HSV-1 DNA was detected in 2 and HSV-2 DNA in 1 of the 3 cases with a nonascending
      pattern. Our findings demonstrate diverse clinical manifestations of HSV
      myelitis.

PMID- 9605394
TI  - Type A behavior and stroke: high tenseness dimension may be a risk factor for
      cerebral infarction.
AB  - Although type A behavior (TAB) has been shown to be related to coronary heart
      disease, the relationship between TAB and stroke was rarely investigated. We
      studied TAB in stroke patients with the use of the questionnaire developed by
      Eysenck and Fulker that has 4 subdimensions: Tenseness, Ambition, Activity, and
      Unrepressed. The questionnaire was administered to 224 patients with acute stroke
      and 100 controls. The patients were further classified as having cerebral
      infarction (large vessel infarction and small vessel infarction), and
      intracerebral hemorrhage. We found that, among the 4 subdimensions, only the
      Tenseness score was significantly higher in patients with cerebral infarction but
      not in those with intracerebral hemorrhage compared to the controls. On subgroup
      analysis, Tenseness score was higher in patients with large vessel infarction but
      not in those with small vessel infarction than in those with intracerebral
      hemorrhage or controls. The association of high Tenseness score with cerebral
      infarction (and large vessel infarction) remained significant after multiple
      logistic analysis adjusting various risk factors such as hypertension, diabetes
      mellitus, cigarette smoking and habitual alcohol drinking. Our data suggest that
      a high Tenseness dimension of TAB may be an independent risk factor for ischemic
      stroke, probably associated with atherogenesis.

PMID- 9605395
TI  - Medial medullary infarction with restricted sensory symptom.
AB  - Sensory abnormalities in patients with medial medullary infarction (MMI) usually
      involve half of the patient's body and extremities. We report 3 patients with
      restricted sensory symptoms due to MMI. Patient 1 had sensory symptoms restricted
      to the contralateral foot secondary to an infarct selectively involving the
      ventral portion of the medial lemniscus that probably corresponds to leg
      representing area. Patient 2 had restricted sensory changes over the
      contralateral perioral area caused by lesions predominantly involving the
      posterior part of the medulla that may have affected a part of the ascending
      trigeminal tract. Patient 3 had sensory symptoms limited to the upper part of his
      body and the arms (pseudosyringomyelia pattern) due to bilateral MMI that may
      have resulted from the ventral-dorsal difference in the severity of the lesion.
      These patients illustrate that restricted sensory abnormalities can occur in
      patients with MMI. Our MRI-clinical correlation study is consistent with the
      previously reported sensory topography of the medial lemniscus and the ascending
      trigeminal tract: the leg-representing area is located ventrally in the medial
      lemniscus whereas the perioral-representing area is situated most medially in the
      ascending trigeminal tract.

PMID- 9605396
TI  - Combined immunoglobulin and azathioprine in multiple sclerosis.
AB  - In an attempt to prevent exacerbations of multiple sclerosis, immunoglobulin
      therapy was combined with azathioprine (AZA). Intravenous immunoglobulin (i.v.IG)
      2 g/kg was given in divided doses over 3 consecutive days followed by monthly
      booster doses (0.2 g/kg) for 3 years to 38 patients with relapsing-remitting
      multiple sclerosis (MS). In the 34 patients who completed the trial, the relapse
      rate decreased (from 1.7 relapses per year to 0 during the 3-year trial period).
      The Kurtzke Expanded Disability Status Scale decreased from 3.4 +/- 0.72 to 3.0
      +/- 0.70. The results suggest that combined i.v.IG and AZA suppress the ongoing
      pathologic process in relapsing-remitting MS.

PMID- 9605397
TI  - Pattern of presentation of multiple sclerosis in Saudi Arabia: analysis based on
      clinical and paraclinical features.
AB  - We studied 89 MS patients comprising 38 males and 51 females seen over a 10-year
      period. The hospital frequency was 25/100,000 patients. The diagnosis was mainly
      clinical and was supported by neuroimaging, cerebrospinal fluid analysis and
      neurophysiological tests. Sixty-five patients (73%) were Saudis and the peak age
      of onset was in the third decade. Fifty-two patients (58.4%) had clinically
      definite MS, 17 (19.1%) had laboratory-supported definite MS, 15 (16.9%) were
      clinically probable MS cases and the remaining 5 (5.6%) had laboratory-supported
      probable MS. The mean age at onset of Saudi patients (25.9 years) was lower than
      that of the non-Saudis (29.4 years; p < 0.001). Involvement of the pyramidal
      system was the commonest mode of presentation. The clinical course was relapsing
      remitting in 60.7%, progressive-relapsing in 20.2% and primary progressive in
      19.1%. The number of systems involved was significantly associated with the
      duration of disease (p < 0.001). The demographic features and the variability of
      clinical presentation of Saudi MS patients is similar to the results from
      neighbouring countries. Combination of clinical features and paraclinical tests
      is essential for accurate determination of extent of dissemination and for
      unmasking clinically silent lesions.

PMID- 9605398
TI  - Acute porphyric neuropathy during pregnancy--effect of haematin therapy.

PMID- 9605399
TI  - Is 75 years too old for carotid endarterectomy? Perioperative mortality and
      stroke risk rates in a series of 80 symptomatic and asymptomatic surgically
      treated patients.

PMID- 9605400
TI  - Long-term treatment of chronic relapsing inflammatory demyelinating
      polyradiculoneuropathy: combination of corticosteroids, plasma exchange, and
      intravenous immunoglobulins.

PMID- 9605401
TI  - MRI of skeletal muscles in autosomal recessive hereditary motor and sensory
      neuropathy with focally folded myelin sheaths.

PMID- 9605402
TI  - A broadening view of recombinational DNA repair in bacteria.
AB  - Recombinational DNA repair is both the most complex and least understood of DNA
      repair pathways. In bacterial cells grown under normal laboratory conditions
      (without a DNA damaging treatment other than an aerobic environment), a
      substantial number (10-50%) of the replication forks originating at oriC
      encounter a DNA lesion or strand break. When this occurs, repair is mediated by
      an elaborate set of recombinational DNA repair pathways which encompass most of
      the enzymes involved in DNA metabolism. Four steps are discussed: (i) The
      replication fork stalls and/or collapses. (ii) Recombination enzymes are
      recruited to the location of the lesion, and function with nearly perfect
      efficiency and fidelity. (iii) Additional enzymatic systems, including the
      phiX174-type primosome (or repair primosome), then function in the origin
      independent reassembly of the replication fork. (iv) Frequent recombination
      associated with recombinational DNA repair leads to the formation of dimeric
      chromosomes, which are monomerized by the XerCD site-specific recombination
      system.

PMID- 9605404
TI  - DNA polymerase epsilon encoded by cdc20+ is required for chromosomal DNA
      replication in the fission yeast Schizosaccharomyces pombe.
AB  - BACKGROUND: DNA polymerase II (PolII), the homologue of mammalian DNA polymerase
      epsilon, is essential for chromosomal DNA replication in the budding yeast
      Saccharomyces cerevisiae and also participates in S-phase checkpoint control. An
      important issue is whether chromosomal DNA replication in other eukaryotes,
      including the fission yeast Schizosaccharomyces pombe--in which the
      characteristics of replication origins are poorly defined--also requires DNA
      polymerase epsilon. It has been shown that DNA polymerase epsilon is not required
      for the in vitro replication of SV40 DNA by human cell extracts. RESULTS: We have
      cloned and sequenced S. pombe pol2+, which is identical to the cell-cycle gene
      cdc20+, encoding the catalytic polypeptide of DNA polymerase epsilon (Pol
      epsilon). The predicted amino acid sequence of Pol epsilon is highly homologous
      to that of S. cerevisiae PolII and human Pol epsilon. Consistent with this, the
      Pol epsilon polypeptide was recognized by polyclonal antibodies against S.
      cerevisiae PolII holoenzyme (PolII*). The terminal morphology of cells containing
      the disrupted pol2 gene was similar to that of DNA replication mutant cells and
      cdc20 mutant cells. Furthermore, the Pol epsilon activity from temperature
      sensitive S. pombe cdc20 mutant cells was temperature-sensitive, and chromosomal
      DNA replication in the mutant cells was inhibited at the restrictive
      temperatures. CONCLUSION: These data strongly suggest that Pol epsilon is
      required for normal chromosomal DNA replication in S. pombe, as is PolII in S.
      cerevisiae. Thus, eukaryotic chromosomal DNA is replicated differently from that
      of viral SV40 DNA.

PMID- 9605403
TI  - Characterization of RecA1332 in vivo and in vitro. A role for alpha-helix E as a
      liaison between the subunit-subunit interface and the DNA and ATP binding domains
      of RecA protein.
AB  - BACKGROUND: The RecA protein of Escherichia coli is essential for homologous
      recombination and induction of the SOS response. RecA has three cysteines located
      at positions 90, 116 and 129. Chemical modification of these residues abolishes
      ATP hydrolysis and repressor cleavage, and causes a reduction in the DNA strand
      exchange and DNA strand annealing activities. Several mutants at each of these
      positions were isolated and partially characterized. One of these, recA1332,
      replaces cysteine 129 with methionine. Although this is a relatively conservative
      mutation based on hydrophobicity, recA1332 was completely defective for DNA
      repair but the purified protein was active for ATPase in vitro. RESULTS: In vivo,
      strains containing this mutant allele were shown to be defective when assayed for
      all RecA-dependent activities. In vitro, RecA1332 protein possessed DNA-dependent
      ATP hydrolysis activity that showed an increased sensitivity to inhibition by
      monovalent cations, and whose k(cat) was reduced 3- to 12-fold. In addition,
      RecA1332 was unable to use oligodeoxyribonulceotides as ssDNA cofactors in the
      ATPase reaction. RecA1332 showed altered binding to single- and double-stranded
      DNA and, although it was able to perform DNA strand exchange, it was slowed in
      its ability to both form joint molecule intermediates and to convert these
      species to product. CONCLUSIONS: Our results are consistent with a defect in
      intermolecular interactions between RecA monomers. We propose that alpha-helix E
      (which includes C129M) is a liaison that connects the subunit-subunit
      interactions to DNA and ATP binding, thereby creating filament stability and
      cooperativity.

PMID- 9605405
TI  - Sendai virus C proteins are categorically nonessential gene products but
      silencing their expression severely impairs viral replication and pathogenesis.
AB  - BACKGROUND: The P/C mRNA of Sendai virus (SeV), a prototypic member of the family
      Paramyxoviridae in the Mononegavirales superfamily comprising a large number of
      nonsegmented negative strand RNA viruses, encodes a nested set of accessory
      proteins, C', C, Y1 and Y2, referred to collectively as C proteins, initiating,
      respectively, at ACG/81 and AUGs/114, 183, 201 in the +1 frame relative to the
      ORF of phospho (P) protein, the smaller subunit of RNA polymerase. Among them, C
      is the major species expressed in infected cells at a molar ratio which is
      several-fold higher than the other three. However, their function has remained an
      enigma. It has not even been established whether or not the C proteins are
      essential for viral replication. Many other viruses in Mononegavirales encode C
      like proteins, but their roles also remain to be defined. RESULTS: By taking
      advantage of a recently developed reverse genetics system to recover infectious
      SeV from cDNA, we created mutants in which C protein frames were variously
      silenced. C/C'(-) viruses which did not express C and C', but did express Y1 and
      Y2, were severely attenuated in replication in tissue culture cells of various
      species and tissues, as well as in embryonated chicken eggs. More notably, they
      were almost totally incapable of growing productively in--and hence nonpathogenic
      for mice--the natural host. Both gene expression and genome replication appeared
      to be impaired in C/C'(-) viruses. Additionally silencing the Y1 and Y2
      expression was also possible, and a critically impaired but viable clone, the 4C(
      ) virus, was isolated which expressed none of the four C proteins. CONCLUSION:
      SeV C proteins are categorically nonessential gene products, but greatly
      contribute to full replication capability in vitro and are indispensable for in
      vivo multiplication and pathogenesis. This study represents the first
      comprehensive functional assessment of the accessary C protein for
      Mononegavirales.

PMID- 9605406
TI  - Identification of receptors and Smad proteins involved in activin signalling in a
      human epidermal keratinocyte cell line.
AB  - BACKGROUND: Activin A is a multifunctional protein, which is a member of the
      transforming growth factor-beta (TGF-beta) superfamily. Smad proteins have
      recently been shown to transduce signals for the TGF-beta superfamily of
      proteins, and Smad2 was implicated in activin signalling in Xenopus embryos.
      RESULTS: We identified the receptors and Smad proteins activated by activin A in
      a human epidermal keratinocyte cell line, HaCaT. The major activin receptors
      expressed on HaCaT cells were activin type II receptor (ActR-II) and activin type
      IB receptor (ActR-IB). We have also shown that in HaCaT cells, activin A induced
      the phosphorylation of Smad3 and, to a lesser extent, of Smad2. On the other
      hand, TGF-beta induced an efficient phosphorylation of both Smad2 and Smad3.
      Activin A preferentially induced the nuclear translocation of Smad3 in HaCaT
      cells, whereas TGF-beta strongly induced the nuclear translocation of Smad2, as
      well as other Smads. Moreover, a constitutively active form of ActR-IB
      efficiently stimulated the formation of a heteromeric complex between Smad3 and
      Smad4 in COS cells transfected with Smad cDNAs. CONCLUSIONS: These results
      suggest that activin A binds to a receptor complex of ActR-II and ActR-IB, and
      preferentially activates Smad3 in HaCaT human keratinocytes.

PMID- 9605407
TI  - Random mutagenesis of human estrogen receptor ligand binding domain identifies
      mutations that decrease sensitivity to estradiol and increase sensitivity to a
      diphenol indene-ol compound: basis for a regulatable expression system.
AB  - We have used low fidelity polymerase chain reaction amplification to generate
      mutations in the human estrogen receptor ligand binding domain (LBD). Screening
      of libraries of mutants in yeast revealed a variety of phenotypic changes
      including decreased responsiveness to estradiol and increased responsiveness to
      synthetic compounds. Identification of the mutations responsible for these
      phenotypic changes indicated discrete regions of the LBD that are important for
      human estrogen receptor function. Cumulative rounds of mutagenesis and screening
      allowed us to produce a mutant estrogen receptor that was of reversed specificity
      as compared with the wild type LBD, in that it was more responsive to a diphenol
      indene-ol than to estradiol. This mutant may form the basis of a useful
      regulatable expression system in mammalian cells.

PMID- 9605408
TI  - Estrogen regulation of transforming growth factor-alpha in ovarian cancer.
AB  - Transforming growth factor alpha (TGFalpha) may be induced by estrogen in
      estrogen responsive systems and can contribute to the growth-modulatory effects
      of this hormone. To test whether TGFalpha contributes to estrogen-regulated
      growth in ovarian cancers, we have compared the effects of 17beta-estradiol (E2)
      and TGFalpha in a range of ovarian carcinoma cell lines. Addition of E2 to the
      estrogen receptor (ER)-positive cell lines (PE01, PE04 and PE01CDDP) produced a 2
      4 fold increase in TGFalpha protein concentrations in media conditioned by the
      cells. Both E2 and TGFalpha stimulated the growth of the PE01 and PE04 lines and
      inhibited the growth of the PE01CDDP line. Furthermore, the E2-mediated growth
      effects could be reversed by an epidermal growth factor (EGF) receptor-targeted
      antibody. E2 also down-regulated EGF receptor expression in ER-positive cell
      lines. In a series of primary ovarian tumors, higher concentrations of ER were
      associated with an increased percentage of tumors expressing TGFalpha mRNA and a
      decreased percentage expressing EGF receptor protein. All these data are
      consistent with E2 increasing production of TGFalpha in ER-positive ovarian
      cancer and this in turn acting through the EGF receptor to modulate growth in an
      autocrine manner.

PMID- 9605409
TI  - Human progesterone receptor A and B isoforms in CHO cells. I. Stable transfection
      of receptor and receptor-responsive reporter genes: transcription modulation by
      (anti)progestagens.
AB  - A hormone-dependent transcription modulation system was established on the basis
      of a two-step transfection procedure of the human progesterone receptor isoforms
      (hPR-A and hPR-B, respectively) and a progesterone receptor-responsive reporter
      (MMTV-Luc). In the first step, stable transfection of the hPR-A and hPR-B isoform
      encoding cDNAs was performed in the steroid receptor-negative CHO K1 cell line.
      Individual clones were characterized for hPR-isoform expression with respect to
      Western immuno-blotting, transcriptional activation and hormone binding. With
      respect to the latter characteristic, individual hPR-isoforms demonstrated
      similar dissociation constants (Kd for hPR-A: 0.5 +/- 0.3 and hPR-B: 0.8 +/- 0.3
      nM, respectively) irrespective of the amount of receptor isoform expressed (Bmax
      varying from 4.1 to 33.2 nM). The Kd values observed for individual hPR-isoforms
      were comparable to those found for human breast tumor MCF-7 cells (Kd for hPR-A +
      hPR-B: 0.6 +/- 0.3 nM). In the second step, hPR-isoform expressing CHO clones
      were supertransfected with a MMTV-Luc reporter construct resulting in permanent
      cell lines useful for testing the activity of natural and synthetic steroids in
      their ability to modulate gene transcription. Both isoform-specific reporter cell
      lines responded in a similar ranking order towards different progesterone
      reference compounds such as Org 2058, progesterone (Prog), R5020, norethisterone
      (NE), and medroxy progesterone acetate (MPA). Moreover, a good correlation was
      observed between the relative binding affinity (RBA) and the transcriptional
      activation potency of these compounds towards the individual hPR-isoforms. The
      latter correlation could not only be demonstrated for the progestagenic agonist
      reference compounds but was also observed for the progestagenic antagonist
      reference compounds like Org 33628, Org 31710, RU 38486 and ZK 98299. The major
      difference observed between the individual PR-isoforms was related to the degree
      of stimulation of the reporter gene (MMTV-based) within the cellular CHO context.
      Therefore, these cell lines can be used for the determination and quantitation of
      the activity of (anti)progestagenic compounds in vitro but may also be useful to
      predict the activity of compounds in vivo (see also II Comparison of binding,
      transactivation and ED50 values of several synthetic (anti) progestagens in vitro
      in CHO and MCF-7 cells and in vivo in rabbits and rats).

PMID- 9605411
TI  - Production and characterization of group-specific monoclonal antibodies
      recognizing nonamidated, glycine- and taurine-amidated ursodeoxycholic acid 7-N
      acetylglucosaminides.
AB  - Ursodeoxycholic acid 7-N-acetylglucosaminides (UDCA 7-NAGs) are novel conjugated
      metabolites whose urine levels are expected to be a specific diagnostic index for
      primary biliary cirrhosis. To obtain a specific antibody which is useful for
      developing immunochemical analytical methods of UDCA 7-NAGs, a variety of
      monoclonal antibodies have been generated. Spleen cells from an A/J mouse, which
      had been immunized with a conjugate of nonamidated UDCA 7-NAG and bovine serum
      albumin, were fused with P3/NS1/1-Ag4-1 myeloma cells. After screening by an
      enzyme-linked immunosorbent assay (ELISA) using a beta-galactosidase-labeled
      antigen, thirteen kinds of antibody-secreting hybridoma clones were established.
      Binding properties of these monoclonal antibodies were investigated in detail by
      ELISA. One of these antibodies, Ab-#8 (gamma1, kappa) had the most favorable
      characteristics for clinical application, which was group-specific to the 7-NAG
      conjugates of nonamidated, glycine- and taurine-amidated UDCAs providing a highly
      sensitive dose-response curve for each conjugate (midpoint 17 pg per assay for
      nonamidated UDCA 7-NAG). Cross-reactivities with eleven kinds of bile acids,
      including some potential interfering metabolites as UDCA 3-sulfate, were
      negligibly low. By using direct ELISA based on Ab-#8, daily urinary excretion
      rates of UDCA 7-NAGs of two healthy subjects were determined to be 1030 and 469
      microg as GUDCA 7-NAG equivalent.

PMID- 9605410
TI  - Human progesterone receptor A and B isoforms in CHO cells. II. Comparison of
      binding, transactivation and ED50 values of several synthetic (anti)progestagens
      in vitro in CHO and MCF-7 cells and in vivo in rabbits and rats.
AB  - The human progesterone receptor A and B isoforms (hPR-A and hPR-B) were stably
      transfected in Chinese Hamster Ovary (CHO) cells in the presence or absence of
      the mouse mamma tumor virus (MMTV) promoter and luciferase (LUC) reporter gene.
      In this way four stably transfected CHO cell lines, i.e. hPR-A, hPR-B, hPR-A-MMTV
      LUC and hPR-B-MMTV-LUC cells, were prepared. hPR-A and -B isoforms were compared
      by binding and transactivation analysis for 14 progestagens and 7
      antiprogestagens. Thereby Org 2058 was used as standard in both agonistic and
      binding assays and Org 31710 in antagonistic assays. The obtained data were
      compared with relative binding affinities (RBA) for both hPR-A and -B, which are
      present in human breast tumor MCF-7 cells, and with biopotency estimations with
      McPhail tests in rabbits and ovulation inhibition and pregnancy interruption
      tests in rats. The relative binding affinities of 14 progestagens and 7
      antiprogestagens towards hPR-A, hPR-B or hPR-A/B of either CHO or MCF-7 cells
      were highly correlated with respect to ranking. This was also shown by the high
      correlation coefficients between the RBA's of hPR-B and hPR-A in CHO cells (r =
      0.983) and between those of hPR-B of CHO and hPR A/B of MCF-7 cells (r = 0.957).
      The transactivation data of the 14 progestagens and 7 antiprogestagens for the
      hPR-B-MMTV-LUC cells were compared with those for hPR-A-MMTV-LUC cells and showed
      no differences between both cell lines with exception of the progestagens Org
      32704 and 33766 and the antiprogestagen Org 33245. Therefore only the relative
      agonistic activities (RAA) and relative antagonistic activities (RANTA) of hPR-B
      MMTV-LUC cells were compared with RBA values of hPR-B, showing a high similarity
      in ranking for the tested compounds, and high correlation coefficients of r =
      0.91 and r = 0.97, respectively. Remarkably, RBA's were 1.6 fold higher than
      RAA's and RANTA's. These in vitro RBA, RAA and RANTA values for hPR-B were
      checked for their pharmacological relevance by in vivo biopotency measurements
      with the 14 progestagens and 7 antiprogestagens in rabbits and rats. The in vitro
      binding and transactivation potencies of progestagens appeared to be very
      predictive for in vivo analysis on endometrium proliferation in rabbits in the
      McPhail test with correlation coefficients of r = 0.81 and r = 0.87, while
      ovulation inhibition in rats correlated less well with r = 0.516 and r = 0.65. On
      the other hand, the antiprogestagenic potencies found with binding and
      transactivation assays had a good correlation with the potencies in the pregnancy
      interruption test in rats for all antiprogestagens tested, being r = 0.849 and r
      = 0.744, respectively. In conclusion, the binding and transactivation potencies
      for the tested compounds in hPR-A and -B containing cell lines showed in general
      a good resemblance. The transactivation studies with hPR-B-MMTV-LUC cells
      indicated that ranking of compounds was fairly identical to binding analysis and
      could be used for pre-screening of the (anti)-progestagenic bioactivity in the
      McPhail test in rabbits, the ovulation inhibition test and the pregnancy
      interruption test in rats. Therefore this transactivation assay can replace
      binding assays. Moreover, direct pre-screening of agonists, antagonists and
      partial antagonists is even possible in this in vitro bioassay, making
      transactivation assays for a particular class of chemical compounds to a valuable
      pre-screening tool for in vivo studies.

PMID- 9605412
TI  - PNU 157706, a novel dual type I and II 5alpha-reductase inhibitor.
AB  - PNU 157706 is a novel dual inhibitor of 5alpha-reductase (5alpha-R), the enzyme
      responsible for the conversion of testosterone (T) to 5alpha-dihydrotestosterone
      (DHT). Tested on a crude preparation of human or rat prostatic 5alpha-R, PNU
      157706 caused enzyme inhibition with IC50 values of 20 and 34 nM, respectively,
      compared to the values of 32 and 58 nM shown by finasteride. Furthermore, PNU
      157706 was highly potent in inhibiting human recombinant 5alpha-R type I and II
      isozymes, showing IC50 values of 3.9 and 1.8 nM and, therefore, it was several
      folds more potent than finasteride (IC50 values of 313 and 11.3 nM), particularly
      on the type I isozyme. PNU 157706 was shown to have no binding affinity for the
      rat prostate androgen receptor (RBA 0.009% that of DHT). In adult male rats, a
      single oral dose of 10 mg/kg of PNU 157706 caused a marked and longer lasting
      reduction of prostatic DHT than did finasteride (at 24 h inhibition by 89 and
      47%, respectively). In prepubertal, T- or DHT-implanted castrated rats, PNU
      157706, given orally for 7 days at the dose of 10 mg/kg/day, markedly reduced
      ventral prostate weight in T- but not in DHT-implanted animals, thus showing to
      be devoid of any anti-androgen activity. In adult rats treated orally for 28
      days, PNU 157706 resulted markedly more potent (16-fold) than finasteride in
      reducing prostate weight, the ED50 values being 0.12 and 1.9 mg/kg/day,
      respectively. These results indicate that PNU 157706 is a promising, potent
      inhibitor of both type II and I human 5alpha-R with a very marked antiprostatic
      effect in the rat.

PMID- 9605413
TI  - Coronary artery and cultured aortic smooth muscle cells express mRNA for both the
      classical estrogen receptor and the newly described estrogen receptor beta.
AB  - Estrogens exhibit potent anti-atherogenic effects through mechanisms which may
      involve direct effects on the artery. The existence of the classical estrogen
      receptor (ERalpha) in vascular tissues has been established. Recently a new
      estrogen receptor (ERbeta) has been discovered which represents a distinct gene
      product with homology to the classical ERalpha. The purpose of the present study
      was to determine if ERbeta mRNA is expressed in vascular tissues of female and
      male primates. Oligonucleotide primers were developed for the specific RT-PCR
      amplification of ERalpha or ERbeta mRNA. RT-PCR products of the appropriate size
      for ERalpha and for ERbeta were observed after amplification of RNA isolated from
      coronary arteries of both male and female cynomolgus monkeys. Similar results
      were obtained from cultured aortic smooth muscle cells and from monkey
      reproductive tissues such as ovary and uterus. The relative expression of ERbeta
      to ERalpha mRNA was greatest in ovary, on the same order of magnitude in monkey
      vascular tissues and uterus, while the human breast cancer cell line MCF-7
      exhibited a very low level of ERbeta relative to ERalpha. Sequence analysis of
      isolated RT-PCR products showed >95% similarity between the monkey and the
      published human sequences for both ERalpha and ERbeta. These findings suggest
      that estrogen may influence vascular gene expression not only through classical
      ERalpha but also through the newly described ERbeta. These findings also
      demonstrate the potential for targeting of these receptors in males for
      prevention or treatment of heart disease.

PMID- 9605414
TI  - Effect of the dual 5alpha-reductase inhibitor PNU 157706 on the growth of dunning
      R3327 prostatic carcinoma in the rat.
AB  - PNU 157706 [N-(1,1,1,3,3,3-hexafluorophenylpropyl)-3-oxo-4-aza-5alpha-androst-1
      ene-17beta-carboxamide] is a novel, potent and selective dual 5alpha-reductase
      inhibitor. We have investigated its effect on tumor growth, endocrine organ
      weights and prostatic dihydrotestosterone (DHT) content in rats bearing the
      androgen dependent Dunning R3327 prostatic carcinoma. Animals with tumor
      diameters of about 1 cm were treated orally for 9 weeks with PNU 157706 (2 and 10
      mg/kg/day, 6 days a week) or they were castrated, to check the hormone
      responsiveness of the tumor. PNU 157706 was effective at both doses tested in
      reducing tumor growth (53 and 51% inhibition at 2 and 10 mg/kg/day,
      respectively), while castration caused higher inhibition (82%) of tumor growth. A
      marked reduction of ventral prostate weight occurred in rats treated with both
      doses of PNU 157706 (75 and 78%) or castrated (91%). Seminal vesicle weight was
      also reduced by PNU 157706 administration (56 and 61% inhibition), whereas
      testes, adrenal, thymus and pituitary weights were not affected. Prostatic DHT
      content was markedly suppressed (85 and 91%) in PNU 157706 treated rats, compared
      to 95% suppression caused by castration. These data support a possible role of
      dual 5alpha-reductase inhibitors in the hormonal therapy of prostatic cancer.

PMID- 9605415
TI  - Binding characteristics of novel nonsteroidal antiestrogens to the rat uterine
      estrogen receptors.
AB  - Tamoxifen (TAM), the only antiestrogen currently available for the endocrine
      therapy of breast cancer behaves as a mixed agonist/antagonist of estrogen
      action, thus limiting its therapeutic potential. We report the binding
      characteristics of a novel series of nonsteroidal antiestrogens to the rat
      uterine estrogen receptor. As measured by competition studies, the affinity of EM
      652, the active metabolite of the prodrug EM-800, for the estrogen receptor is 7
      11 times higher than that of 17beta-estradiol (E2), ICI 182780, and hydroxy
      tamoxifen (OH-TAM), the active metabolite of Tamoxifen. EM-652 is 20x more potent
      than ICI 164384 and Droloxifene while it is 400 times more potent than Toremifene
      in displacing [3H]E2 from the rat uterine estrogen receptor. On the other hand,
      the prodrug EM-800 and Tamoxifen have respectively 150-fold and 410-fold less
      affinity for the estrogen receptor than the pure antiestrogen EM-652. No
      significant binding of EM-652, EM-800, TAM or OH-TAM was observed to the rat
      uterine progesterone receptor at concentrations up to 10,000 nM except for TAM
      that caused a 50% displacement of labeled R5020 at 4000 nM. No significant
      binding of EM-652 or EM-800 was observed on the rat ventral prostate androgen
      receptor or the rat uterine progesterone receptor. The present data demonstrate
      the high affinity and specificity of the new antiestrogen, EM-652, for the rat
      uterine estrogen receptor. The antiestrogen EM-652 thus becomes the compound
      having the highest known affinity for the estrogen receptor. Due to its unique
      potency and its pure antiestrogenic activity already demonstrated in many
      systems, this antiestrogen could well offer an important advance for the
      endocrine therapy of breast cancer, uterine cancer, and other estrogen-sensitive
      diseases in women.

PMID- 9605416
TI  - Effects of tea polyphenols and flavonoids on liver microsomal glucuronidation of
      estradiol and estrone.
AB  - Administration of 0.5 or 1% lyophilized green tea (5 or 10 mg tea solids per ml,
      respectively) as the sole source of drinking fluid to female Long-Evans rats for
      18 days stimulated liver microsomal glucuronidation of estrone, estradiol and 4
      nitrophenol by 30-37%, 15-27% and 26-60%, respectively. Oral administration of
      0.5% lyophilized green tea to female CD-1 mice for 18 days stimulated liver
      microsomal glucuronidation of estrone, estradiol and 4-nitrophenol by 33-37%, 12
      22% and 172-191%, respectively. The in vitro addition of a green tea polyphenol
      mixture, a black tea polyphenol mixture or (-)-epigallocatechin gallate inhibited
      rat liver microsomal glucuronidation of estrone and estradiol in a concentration
      dependent manner and their IC50 values for inhibition of estrogen metabolism were
      approximately 12.5, 50 and 10 microg/ml, respectively. Enzyme kinetic analysis
      indicates that the inhibition of estrone glucuronidation by 10 microM (-)
      epigallocatechin gallate was competitive while inhibition by 50 microM (-)
      epigallocatechin gallate was noncompetitive. Similarly, several flavonoids
      (naringenin, hesperetin, kaempferol, quercetin, rutin, flavone, alpha
      naphthoflavone and beta-naphthoflavone) also inhibited rat liver microsomal
      glucuronidation of estrone and estradiol to varying degrees. Naringenin and
      hesperetin displayed the strongest inhibitory effects (IC50 value of
      approximately 25 microM). These two hydroxylated flavonoids had a competitive
      mechanism of enzyme inhibition for estrone glucuronidation at a 10 microM
      inhibitor concentration and a predominantly noncompetitive mechanism of
      inhibition at a 50 microM inhibitor concentration.

PMID- 9605417
TI  - The measurement of the isoflavone daidzein by time resolved fluorescent
      immunoassay: a method for assessment of dietary soya exposure.
AB  - We report a novel method for the measurement of urinary daidzein that is suitable
      for assessment of dietary soya exposure. The method incorporates the following
      features: (i) a highly specific monoclonal antibody to daidzein (clone 4E4)
      raised through the 7 position of daidzein and (ii) a europium labeled ovalbumin
      daidzein conjugate. In the present format, dilute urine samples of subjects who
      ingested soy milk are hydrolyzed with beta-glucuronidase for 30 min on rabbit
      anti-mouse coated plates. Afterwards, the specific monoclonal antibody to
      daidzein, clone 4E4, and europium labeled ovalbumin daidzein conjugate are added.
      After 1 h incubation, the wall bound fluorescence of europium is measured by time
      resolved fluorescence and is inversely proportional to the concentration of
      daidzein over the range 0.1-10 ng daidzein/well. The method demonstrates good
      sensitivity, precision and comparability with the chemical method GC-FID. Unlike
      the chemical method, the present immunoassay technique for daidzein is applicable
      for the measurement of large amounts of samples in epidemiological studies for
      the assessment and monitoring of human exposure to soya food.

PMID- 9605418
TI  - Adaptive response to DNA-damaging agents: a review of potential mechanisms.
AB  - The study of the adaptive response, i.e. a reduced effect from a higher
      challenging dose of a stressor when a smaller inducing dose had been applied a
      few hours earlier, has opened many new vistas into the mechanisms by which cells
      can adapt to hazardous environments. Although the entire chain from the initial
      event, supposedly the presence of DNA damage, to the end effect, presumably
      improved DNA repair, has not been fully elucidated, many individual links have
      been postulated. Initial elements--following the still unknown signal for the
      presence of radiation damage--are various kinases (protein kinase C and stress
      activated protein kinases), which, in turn, induce early response genes whose
      products initiate a cascade of protein-DNA interactions that regulate gene
      transcription and ultimately result in specific biological responses. These
      responses include the activation of later genes that can promote production of
      growth factors and cytokines, trigger DNA repair, and regulate progress through
      the cell cycle. Indeed, there appears to be a relation between the induction of
      the adaptive response and the effects of radiation and cytostatic agents on the
      cell cycle, although these effects, especially the G1 delay, occur at much higher
      doses than the adaptive response, and one may not indiscriminately extrapolate
      mechanisms responsible for cell cycle changes observed at high doses, e.g. for
      radiation in the order of grays, to those involved in the adaptive responses at
      much lower doses, i.e. some tens of milligrays.

PMID- 9605419
TI  - Regulation of cellular and system function by activin.
AB  - Activin is an important molecule that regulates hormonogenesis, cellular
      homeostasis (divide or die pathways), and differentiation programs
      (developmentally and in adult cells). The cellular mechanisms that integrate an
      activin signal into a physiological response include a binary receptor complex
      and tandem serine threonine kinases, intracellular signal mediators, and nuclear
      transcription factors. Activin antagonists (inhibins) and bioneutralizing binding
      proteins (follistatins) act as gating molecules to ensure accurate delivery of
      activin signals to cellular machinery. Correct execution of an activin cue
      intracellularly permits actions as fundamental as embryonic mesoderm development,
      neuronal survival, hematopoietic function, and reproductive cyclicity. Absent or
      incorrect activin signaling results in phenotypes as catastrophic as embryonic
      lethality, tumor formation, and infertility. The general ways in which a cell
      senses and responds to an activin signal will be reviewed in the first part of
      this paper. The role of this ligand in reproductive function will also be
      examined as a specific example of activin activity.

PMID- 9605420
TI  - Inhibition of nuclear factor kappaB by direct modification in whole cells-
      mechanism of action of nordihydroguaiaritic acid, curcumin and thiol modifiers.
AB  - This study was set up to investigate the mechanism of four inhibitors of
      interleukin-1(IL-1)-alpha and tumor necrosis factor-(TNF)alpha activated nuclear
      factor kappaB (NFkappaB) in whole cells. The compounds fall into two classes: the
      first comprised two chain-breaking antioxidants, curcumin (diferulolylmethane)
      and nordihydroguaiaritic acid. The second class were two thiol-modifying agents,
      N-ethylmaleimide (NEM) and 2-chloro-1,3dinitrobenzene (CDNB). Both sets of
      compounds were found to inhibit NFkappaB in tumour necrosis factor-activated
      Jurkat T lymphoma cells and interleukin 1-activated EL4.NOB-1 thymoma cells as
      determined by electrophoretic mobility shift assay using a specific NFkappaB DNA
      probe. In unstimulated cells the compounds were found to modify NFkappaB prior to
      chemical dissociation with sodium deoxycholate. They also inhibited DNA binding
      by NFkappaB when added to nuclear extracts from stimulated cells. Both of these
      effects occurred over a concentration range comparable to that which inhibited
      cytokine-activated NFkappaB in intact cells. All four agents were found to react
      directly with the p50 subunit of NFkappaB. However, only the antioxidants,
      curcumin and nordihydroguaiaritic acid (NDGA) were found to inhibit IkappaBalpha
      degradation activated by tumour necrosis factor-alpha. These results suggest that
      NFkappaB itself is susceptible to direct inhibition by a range of pharmacological
      agents. Furthermore, curcumin and nordihydroguaiaritic acid inhibit NFkappaB by
      interfering with IkappaBalpha degradation and reacting with p50 in the NFkappaB
      complex. These findings are likely to be useful in the attempt to develop agents
      which inhibit NFkappaB-dependent gene transcription.

PMID- 9605421
TI  - Suppression of inflammatory responses by surfactin, a selective inhibitor of
      platelet cytosolic phospholipase A2.
AB  - Surfactin inhibits platelet and spleen cytosolic 100 kDa phospholipase A2 (PLA2).
      In contrast, this same compound enhances rat platelet group II PLA2 activity by
      approximately 2-fold and slightly increases group I PLA2 activity from porcine
      pancreas and Naja naja venom in vitro. Surfactin does not affect a Ca2+ 
      independent PLA2 partially purified from bovine brain. Thus, this compound
      inhibits selectively the cytosolic form of PLA2. Based on in vitro studies
      utilizing preincubation of surfactin with the enzyme, dialysis, and increased
      concentrations of substrates, the inhibitory effect of surfactin appears to be
      due to a direct interaction with the enzyme. Linear regression analysis of the
      linear portion of a concentration-response curve reveals an IC50 of 8.5 microM.
      To further determine the inhibitory pattern, a Dixon plot was constructed to show
      that the inhibition by surfactin is competitive, but not uncompetitive, with an
      inhibition constant of Ki = 4.7 microM in 50 mM Tris-HCl buffer, pH 8.0, at 37
      degrees. Surfactin blocked non-stimulated and calcium ionophore A23187-stimulated
      release of arachidonic acid from monkey kidney CV-1 cells, which contain a
      cytosolic 100 kDa PLA2 as the major activity, as shown in an anionic exchange
      DEAE-5PW high performance liquid chromatography profile and western blotting
      analysis. Surfactin ameliorated inflammation induced by several chemicals. That
      is, it exhibited in vivo anti-inflammatory activity in several tested
      inflammatory reactions including 12-O-tetradecanoylphorbol-13-acetate (TPA)
      induced mouse ear edema, carrageenan-induced rat paw edema, and acetic acid
      induced mouse writhing. These results demonstrate that surfactin is a selective
      inhibitor for cytosolic PLA2 and a putative anti-inflammatory agent through the
      inhibitory effect produced by direct interaction with cytosolic PLA2, and that
      inhibition of cytosolic PLA2 activity may suppress inflammatory responses.

PMID- 9605422
TI  - Mechanisms of inhibition of the thioredoxin growth factor system by antitumor 2
      imidazolyl disulfides.
AB  - The interactions of a series of 2-imidazolyl disulfide antitumor compounds with
      the thioredoxin reductase(TR)/thioredoxin (hTrx) redox system have been studied.
      Disulfides III-2 (n-butyl 2-mercaptoimidazolyl disulfide) and VI-2 (ethyl 2
      mercaptoimidazolyl disulfide) were substrates for reduction by TR with Km values
      of 43 and 48 microM. Disulfides IV-2 (1-methylpropyl 2-mercaptoimidazolyl
      disulfide) and DLK-36 (benzyl 2-mercaptoimidazolyl disulfide) were competitive
      inhibitors of the reduction of hTrx by TR with Ki values of 31 microM. None of
      the disulfides were substrates for reduction by human glutathione reductase. The
      disulfides caused reversible thioalkylation of hTrx at the redox catalytic site
      as shown by the fact that there was no thioalkylation of a mutant hTrx where both
      the catalytic site Cys32 and Cys35 residues were replaced by Ser. In addition,
      the disulfides caused a slower irreversible inactivation of hTrx as a substrate
      for reduction by TR, with half-lives for III-2 of 30 min, for IV-2 of 4 hr, and
      for IX-2 (t-butyl 2-mercaptoimidazolyl disulfide) of 24 hr. This irreversible
      inactivation of hTrx occurred at concentrations of the disulfides an order of
      magnitude below those that inhibited TR, and involved the Cys73 of hTrx, which is
      outside the conserved redox catalytic site, as shown by the resistance to
      inactivation of a mutant hTrx where Cys73 was replaced by Ser. Electrophoretic
      and mass spectral analyses of the products of the reaction between the disulfides
      and hTrx show that modification of 1-3 Cys residues of the protein occurred in a
      concentration-dependent fashion. The disulfides inhibited the hTrx-dependent
      proliferation of MCF-7 breast cancer cells with IC50 values for III-2 and IV-2 of
      0.2 and 1.2 microM, respectively. The results show that although the catalytic
      sites of TR and hTrx are reversibly inhibited by the 2-imidazolyl disulfides, it
      is the irreversible thioalkylation of Cys73 of hTrx by the disulfides that most
      probably accounts for the inhibition of thioredoxin-dependent cell growth by the
      disulfides.

PMID- 9605423
TI  - Different moieties of tautomycin involved in protein phosphatase inhibition and
      induction of apoptosis.
AB  - The effects of tautomycin and its derivatives on protein phosphatases PP1 and
      PP2A and their apoptosis-inducing activity toward human leukemia Jurkat cells
      were examined, and the relationship between chemical structure and function was
      discussed. Among the compounds we examined, tautomycin was the most potent
      inhibitor and the most effective inducer of apoptosis. It inhibited PP1 and PP2A
      enzymatic activity concentration-dependently with IC50 values of 20 and 75 pM,
      respectively, in the presence of 0.01% Brij-35, and an LC50 value of 1 microM.
      Esterification of the anhydride moiety of tautomycin markedly increased the IC50
      for the protein phosphatases. The C1'-C7' fragment of tautomycin had no
      inhibitory effect, but the fragment containing the C22-C26 moiety was inhibitory.
      These results suggest that the C22-C26 moiety is essential for inhibition of
      protein phosphatase activity and that the anhydride moiety enhances the
      inhibition. However, the esterification of the anhydride did not decrease, nor
      did the inclusion of the C22-C26 moiety increase the apoptosis-inducing activity.
      On the other hand, the C1-C18 moiety of tautomycin was essential for induction of
      apoptosis, and the conformation and the arrangement of functionalities of the C18
      C26 carbon chain affected the apoptosis activity. However, modification of C1
      C18, C1-C21, or C1-C26 compounds had little effect on phosphatase inhibitory
      activity. Our results strongly suggest that different moieties of tautomycin are
      involved in protein phosphatase inhibition and induction of apoptosis.

PMID- 9605424
TI  - Drug glucuronidation by human renal UDP-glucuronosyltransferases.
AB  - The UDP-glucuronosyltransferases catalyse the conjugation of glucuronic acid to a
      wide variety of endobiotics and xenobiotics, representing one of the major
      conjugation reactions in the conversion of both exogenous (e.g. drugs and
      pesticides) and endogenous compounds (e.g. bilirubin and steroid hormones). The
      liver is the major site of glucuronidation, however a number of extrahepatic
      tissues exhibit particular UDP-glucuronosyltransferase activities. The present
      study was undertaken to assess the human renal UDP-glucuronosyltransferase
      system. Enzymatic analysis of human kidney showed that a limited number of UDP
      glucuronosyltransferase isoforms were expressed in this tissue. However the level
      of renal UGT activity towards the anaesthetic propofol was higher compared with
      human liver. The glucuronidation of propofol is catalysed by UGT1A8/9 suggesting
      higher levels of this isoform in the kidney. Immunoblot analysis revealed two
      major UDP-glucuronosyltransferase immunopositive bands to be present in human
      kidney as compared to four major bands in human liver. The human kidney was
      capable of conjugating various structurally diverse drugs and xenobiotics.

PMID- 9605425
TI  - Inhibition of the cyclic AMP signaling cascade and nuclear factor binding to CRE
      and kappaB elements by cannabinol, a minimally CNS-active cannabinoid.
AB  - Immune suppression by cannabinoids has been widely demonstrated in a variety of
      experimental models. The identification of two major types of G-protein-coupled
      cannabinoid receptors expressed on leukocytes, CB1 and CB2, has provided a
      putative mechanism of action for immune modulation by cannabinoid compounds.
      Ligand binding to both receptors negatively regulates adenylate cyclase, thereby
      lowering intracellular cyclic AMP (cAMP) levels. In the present studies, we
      demonstrated that cannabinol (CBN), a ligand that exhibits higher binding
      affinity for CB2, modulates immune responses and cAMP-mediated signal
      transduction in mouse lymphoid cells. Direct addition of CBN to naive cultured
      splenocytes produced a concentration-dependent inhibition of lymphoproliferative
      responses to anti-CD3, lipopolysaccharide, and phorbol-12-myristate-13
      acetate/ionomycin stimulation. Similarly, a concentration-related inhibition of
      the in vitro anti-sheep red blood cell IgM antibody forming cell response was
      also observed by CBN. Evaluation of cAMP signaling in the presence of CBN showed
      a rapid and concentration-related inhibition of adenylate cyclase activity in
      both splenocytes and thymocytes. This decrease in intracellular cAMP levels
      produced by CBN resulted in a reduction of protein kinase A activity,
      consequently leading to an inhibition of transcription factor binding to the cAMP
      response element and kappaB motifs in both cell preparations. Collectively, these
      results demonstrate that CBN, a cannabinoid with minimal CNS activity, inhibited
      both cAMP signal transduction and immune function, further supporting the
      involvement of CB2 receptors in immune modulation by cannabimimetic agents.

PMID- 9605426
TI  - Anthracycline antibiotic blockade of SV40 T antigen helicase action.
AB  - We previously showed that anthracycline antibiotics potently block SV40 large T
      antigen helicase; in the present study, we describe the kinetics and the
      structure-activity characteristics of this process. The concentration vs effect
      data for helicase blockade were fitted by the Hill equation to yield nearly
      parallel log-concentration effect curves for a series of active anthracycline
      antibiotics. The effective concentration for 50% helicase blockade (EC50) values
      ranged from 0.34 microM for daunorubicin to 40.8 microM for 3'
      deaminodaunorubicin. Clinically inactive 3'-N-acyl anthracyclines produced no
      blockade. The Hill constants for the blockade ranged from 1.1 to 1.6 for the
      entire series of active anthracyclines, indicating no positive cooperativity and
      suggesting that a single molecule of bound drug is sufficient to block helicase
      action. The EC50 values for several clinically effective anthracyclines showed a
      relationship to the average DNA binding constants for these drugs, and Lineweaver
      Burk analysis of the blockade kinetics indicated non-competitive inhibition. The
      kinetics of the blockade indicated that the anthracycline, DNA, and helicase form
      a ternary complex that is irreversible under the reaction conditions. This
      mechanism may be central to the cytotoxic and anti-cancer activities of
      anthracycline antibiotics and may be useful in understanding the enzymatic
      mechanism of DNA helicase action.

PMID- 9605427
TI  - Ligand efficacy and potency at recombinant alpha2 adrenergic receptors: agonist
      mediated [35S]GTPgammaS binding.
AB  - Alpha-2 adrenergic receptors (alpha2 AR) mediate incorporation of guanosine 5'-O
      (gamma-thio)triphosphate ([35S]GTPgammaS) into isolated membranes via receptor
      catalyzed exchange of [35S]GTPgammaS for GDP. In the current study, we used
      [35S]GTPgammaS incorporation to characterize the intrinsic activity and potency
      of agonists and antagonists at the cloned mouse alpha2a/d and human alpha2a,
      alpha2b, and alpha2c ARs. Full agonists increased [35S]GTPgammaS binding to
      membranes by 2- to 3-fold. Antagonists did not increase [35S]GTPgammaS binding
      but competitively inhibited agonist-stimulated [35S]GTPgammaS binding. Compounds
      with intrinsic activities less than that of the full agonists norepinephrine (NE)
      or epinephrine (EPI) were capable of antagonizing agonist-stimulated
      [35S]GTPgammaS binding. The agonistic properties of a number of alpha2 AR ligands
      were characterized at each alpha2 AR subtype. The rank order of agonist potency
      for selected compounds at the human receptors (with intrinsic activity compared
      with NE, defined as 1.0) was: alpha2a: Dexmedetomidine (0.73) > guanabenz (0.38)
      > UK-14304 (1.02) > clonidine (0.32) > ST-91 (0.63) > NE (1.00). alpha2b:
      Dexmedetomidine (1.10) > clonidine (0.18) > guanabenz (0.71) > NE (1.00) > ST-91
      (0.44) > UK-14304 (0.59). alpha2c: Dexmedetomidine (1.03) > NE (1.00) > UK-14304
      (0.75) > ST-91 (0.32) > or = clonidine (0.23) >> guanabenz (0). This report
      provides a functional characterization of adrenergic receptor ligands at human
      and mouse alpha2a/d AR. It also illustrates the utility of [35S]GTPgammaS
      incorporation as a functional marker of receptor activation.

PMID- 9605428
TI  - Identification and characterization of a novel delta6/delta5 fatty acid
      desaturase inhibitor as a potential anti-inflammatory agent.
AB  - The anti-inflammatory properties of essential fatty acid deficiency or n-3
      polyunsaturated fatty acid supplementation have been attributed to a reduced
      content of arachidonic acid (AA; 20:4 n-6). An alternative, logical approach to
      depleting AA would be to decrease endogenous synthesis of AA by selectively
      inhibiting the delta5 and/or the delta6 fatty acid desaturase. High-throughput
      radioassays were developed for quantifying delta5, delta6, and delta9 desaturase
      activities in vitro and in vivo. CP-24879 (p-isopentoxyaniline), an aniline
      derivative, was identified as a mixed delta5/delta6 desaturase inhibitor during
      the screening of chemical and natural product libraries. In mouse mastocytoma
      ABMC-7 cells cultured chronically with CP-24879, there was a concentration
      dependent inhibition of desaturase activity that correlated with the degree of
      depletion of AA and decreased production of leukotriene C4 (LTC4). Production of
      LTC4 was restored by stimulating the cells in the presence of exogenous AA,
      indicating that endogenous AA was limiting as substrate. In the livers of mice
      treated chronically with the maximally tolerated dose of CP-24879 (3 mg/kg,
      t.i.d.), combined delta5/delta6 desaturase activities were inhibited
      approximately 80% and AA was depleted nearly 50%. These results suggest that
      delta5 and/or delta6 desaturase inhibitors have the potential to manifest an anti
      inflammatory response by decreasing the level of AA and the ensuing production of
      eicosanoids.

PMID- 9605429
TI  - Effects of chemical inducers on human microsomal epoxide hydrolase in primary
      hepatocyte cultures.
AB  - Human microsomal epoxide hydrolase (mEH; EC 3.3.2.3) is an important
      biotransformation enzyme and potential risk determinant for pathologies such as
      cancer and teratogenesis. Currently, the effects of chemical exposures on human
      mEH gene expression are largely unknown, but they may constitute a unique
      modifier of disease susceptibility. To examine this issue, we exposed cultures of
      primary human hepatocytes isolated from seven donors to prototypic chemical
      inducers [such as phenobarbital (PB), polyaromatic hydrocarbons, dexamethasone,
      butylated hydroxyanisole, and ciprofibrate]. Basal levels of mEH RNA and protein
      were detected readily in untreated cells. Chemical treatment of cultured
      hepatocytes resulted in variable mEH RNA and protein expression, but, in general,
      only modest modulatory effects were detected following these exposures. The
      maximum increase in mEH RNA expression observed was approximately 3.5-fold
      following Arochlor 1254 exposure. Immunochemical levels of mEH protein were
      quantified for all treatment groups in three cultures and demonstrated less
      overall variation and, in general, a lack of concordance with corresponding mEH
      RNA levels. Cytochrome P450 (CYP) 1A2 and 3A mRNA levels were measured before and
      following exposure to beta-naphthaflavone and PB, respectively, to permit
      independent evaluation of hepatocyte inducer responsiveness. Substantial
      increases in RNA expression levels for both the CYP1A2 and CYP3A genes
      demonstrated that the hepatocyte cultures were robust and highly responsive to
      inducer treatment. These results indicate that the mEH gene in human hepatocytes
      is only modestly responsive to chemical exposures.

PMID- 9605430
TI  - Inhibitory effect of mast cell-mediated immediate-type allergic reactions in rats
      by spirulina.
AB  - We investigated the effect of spirulina on mast cell-mediated immediate-type
      allergic reactions. Spirulina dose-dependently inhibited the systemic allergic
      reaction induced by compound 48/80 in rats. Spirulina inhibited compound 48/80
      induced allergic reaction 100% with doses of 100-1000 microg/g body weight, i.p.
      Spirulina (10-1000 microg/g body weight, i.p.) also significantly inhibited local
      allergic reaction activated by anti-dinitrophenyl (DNP) IgE. When rats were
      pretreated with spirulina at a concentration ranging from 0.01 to 1000 microg/g
      body weight, i.p., the serum histamine levels were reduced in a dose-dependent
      manner. Spirulina (0.001 to 10 microg/mL) dose-dependently inhibited histamine
      release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti
      DNP IgE. The level of cyclic AMP in RPMC, when spirulina (10 microg/mL) was
      added, transiently and significantly increased about 70-fold at 10 sec compared
      with that of control cells. Moreover, spirulina (10 microg/mL) had a significant
      inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-alpha production.
      These results indicate that spirulina inhibits mast cell-mediated immediate-type
      allergic reactions in vivo and in vitro.

PMID- 9605431
TI  - Interruption of estradiol signal transduction by 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) through disruption of the protein phosphorylation pathway in
      adipose tissues from immature and mature female rats.
AB  - At doses of 10-115 microg/kg, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
      decreased body and adipose tissue weights of mature female rats. Doses below 10
      microg TCDD/kg decreased body and adipose tissue weights of immature, but not
      mature females. Doses of 2 and 10 microg TCDD/kg decreased adipose tissue
      epidermal growth factor receptor (EGFR) binding activity 5 and 7 days later in
      immature and mature females, respectively. At these times, there was a decrease
      in the activities of tyrosine kinase (TK), mitogen-activated protein kinase
      (MAP2K), and protein kinase A (PKA). In mature females, estradiol (E2, 15
      microg/kg) increased TK and PKA activities and decreased MAP2K activity. In
      immature females, E2 decreased TK and PKA activities but not MAP2K activity. TCDD
      abolished the stimulatory effect of E2 on TK and PKA in mature females, and in
      immature females TCDD potentiated the negative effect of E2 on all three kinases.
      TCDD decreased binding of [3H]E2 to cytosolic and nuclear estrogen receptors
      (ERs) of mature and immature females, and antagonized the stimulatory effect of
      E2 on ER binding activity. E2 increased DNA binding activity of the estrogen
      response element (ERE) and activator protein-1, and TCDD antagonized this effect.
      Geldanamycin, an inhibitor of Src tyrosine kinase, reduced the effects of TCDD on
      body and adipose tissue weights. Geldanamycin antagonized the effects of TCDD on
      EGFR binding activity and TK activity. In cell-free preparations, TCDD
      antagonized E2 action on TK activity in mature females, as well as E2 action on
      PKA activity in immature females. We hypothesize that TCDD antagonizes E2 action
      in female adipose tissues through disruption of common cytosolic signal
      transduction pathways.

PMID- 9605432
TI  - Tumor selective delivery of 5-fluorouracil by capecitabine, a new oral
      fluoropyrimidine carbamate, in human cancer xenografts.
AB  - Capecitabine (N4-pentyloxycarbonyl-5'-deoxy-5-fluorocytidine) is a novel
      fluoropyrimidine carbamate that is converted to 5-fluorouracil (5-FUra) by three
      enzymes located in the liver and tumors; the final step is the conversion of 5'
      deoxy-5-fluorouridine (5'-dFUrd) to 5-FUra by thymidine phosphorylase in tumors.
      The present study compared the efficacy of capecitabine and 5-FUra at their
      maximum tolerated doses in CXF280, HCT116, COLO205, and WiDr human colon cancer
      xenograft models, and measured subsequent 5-FUra and 5'-dFUrd levels in tumors
      and in the plasma and muscle. Capecitabine was effective in the first three
      models, whereas 5-FUra was effective only in CXF280, which is a cell line highly
      susceptible to fluoropyrimidines. In the three susceptible models, 5-FUra AUCs in
      tumors after capecitabine administration were 210 to 303 nmol x hr/g, whereas
      those after 5-FUra administration were 8.54 to 13.1 nmol x hr/g. In addition,
      capecitabine gave higher levels of 5-FUra AUC in tumors than in plasma (114- to
      209-fold higher) and muscle (21.6-fold higher), whereas 5-FUra was not
      selectively distributed to tumors. In the refractory model, WiDr, 5-FUra AUC in
      tumors after capecitabine administration was only 62.8 nmol x hr/g, although the
      level of the intermediate metabolite 5'-dFUrd was high (AUC: 695 nmol x hr/g).
      The ratio of 5-FUra/5'-dFUrd levels in the WiDr tumors was 0.09, which was 23.8
      fold lower than that in the HCT116 tumors. The mechanism of resistance would be
      the inefficient conversion of 5'-dFUrd to 5-FUra by thymidine phosphorylase in
      tumors. Thus, capecitabine might show its high efficacy as a result of delivering
      high levels of 5-FUra selectively to the tumors.

PMID- 9605433
TI  - Inhibition of recombinant human mitochondrial aldehyde dehydrogenase by two
      intermediate metabolites of disulfiram.
AB  - Disulfiram is used in aversion therapy for alcoholism. S-Methyl-N,N
      diethylthiocarbamate (MeDTC) sulfoxide, a potent inhibitor of the target enzyme
      mitochondrial aldehyde dehydrogenase (ALDH2), is thought to be the principal
      active metabolite of disulfiram in vivo. We examined the effects on recombinant
      human ALDH2 of two intermediate metabolites of disulfiram, S-methyl-N,N
      diethyldithiocarbamate (MeDDC) sulfoxide and MeDDC sulfine. MeDDC sulfoxide was a
      potent inhibitor of ALDH2 with an IC50 of 2.2 +/- 0.5 microM (mean +/- SD, N = 4)
      after preincubation with enzyme for 30 min. MeDDC sulfine was a relatively weak
      inhibitor of ALDH2 under the same conditions with an IC50 value of 62 +/- 14
      microM. The inhibition of ALDH2 by both compounds was irreversible and did not
      require the cofactor NAD. The latter finding demonstrates that inactivation of
      ALDH2 is independent of the dehydrogenase activity of the enzyme. GSH blocked
      almost completely the inhibition by 20 microM of MeDDC sulfoxide and greatly
      diminished the inhibition by 200 microM of MeDDC sulfine. Inactivation by MeDDC
      sulfoxide was time dependent. MeDTC sulfoxide was a more potent inhibitor of
      recombinant human ALDH2 (IC50 = 1.4 +/- 0.3 microM after preincubation for 15
      min) than either of the intermediate metabolites, and its inhibition was
      unaffected by GSH. Our results suggest that these newer intermediate metabolites
      of disulfiram, especially the more potent MeDTC sulfoxide, have the potential to
      inhibit the target enzyme ALDH2 in patients receiving disulfiram. However, until
      the significance of the interactions of the inhibitors with GSH is more fully
      understood, the contribution of MeDDC sulfine and MeDDC sulfoxide to the
      pharmacological effects of disulfiram in vivo is uncertain.

PMID- 9605434
TI  - Modulation of ceramide-activated protein phosphatase 2A activity by low molecular
      weight aromatic compounds.
AB  - Protein phosphatase 2A (PP2A) is one of the most important and abundant
      serine/threonine phosphatases in mammalian tissues and plays a role in gene
      expression, cell division, and signal transduction. PP2A is activated by
      ceramide, which is produced by the hydrolysis of membrane sphingomyelin in
      response to a variety of stress-related stimuli. To further study the role of
      ceramide-mediated signal transduction in cellular processes such as senescence
      and apoptosis, we designed and synthesized a series of low molecular weight
      aromatic compounds, mainly of the isoquinolone and tetralone classes, and
      evaluated their ability to inhibit enzymes known to be activated by ceramide.
      Those enzymes studied were ceramide-activated protein kinase, protein kinase C
      zeta and PP2A. Of these, only PP2A was found to be inhibited. A few of the
      compounds inhibited both ceramide-activated as well as basal PP2A activity. In
      addition, several of the compounds activated PP2A by up to 300% above basal
      enzyme activity, but only in the presence of ceramide. Thus, modulation (both
      inhibition and activation) of the catatylic activity of ceramide-activated PP2A
      is demonstrated by certain low molecular weight aromatic compounds.

PMID- 9605435
TI  - Relationship between nitric oxide and prostaglandins in carrageenin pleurisy.
AB  - The correlation between endogenous nitric oxide (NO) generation and prostaglandin
      biosynthesis was studied in rat carrageenin pleurisy induced by the injection of
      0.2 mL of 1% lambda-carrageenin into the pleural cavity. The pleural exudate was
      collected at 4 hr and the amounts of NO2- + NO3- (NOx) and prostaglandin E2
      (PGE2) measured. The NOx present in the inflammatory exudate was determined by
      measuring the NO2- with the Griess reaction, after the reduction of NO3- to NO2-
      using acid-washed cadmium powder. PGE2 was measured by radioimmunoassay. The NO
      synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 1-3-10 mg/kg
      subcutaneously) reduced NOx by 20 +/- 7%, 41 +/- 6% and 55 +/- 9% (P < 0.01) and
      PGE2 by 9 +/- 6%, 41 +/- 11% and 74 +/- 9% (P < 0.001). Conversely, L-arginine
      (300 mg/kg SC) increasedNOx by 39 +/- 7% (P < 0.01) and PGE2 by 78 +/- 6% (P <
      0.001). The NO scavenger haemoglobin (Hb), coinjected into the pleural cavity (3
      mg/site) with carrageenin, produced a parallel inhibition of NOx (65 +/- 16%, P <
      0.001) and PGE2 (71 +/- 18%, P < 0.001). The soluble guanylate cyclase inhibitor
      methylene blue (Mb; 2 mg/site) had no effect. Moreover haemoglobin, but not
      methylene blue, was able to significantly suppress the L-arginine-induced
      increase of both NOx and PGE2. In each pleural exudate, independently from the
      animal treatment, the amount of NOx was highly correlated to the amount of PGE2
      (r = 0.93, P < 0.001). These results suggest that in rat carrageenin pleurisy the
      modulation of the L-arginine:NO pathway results in a parallel modulation of
      prostaglandin biosynthesis. The interaction between cyclooxygenase and the NO
      pathway may represent an important mechanism for the modulation of the
      inflammatory response.

PMID- 9605436
TI  - Induction of spermidine/spermine N1-acetyltransferase in human cancer cells in
      response to increased production of reactive oxygen species.
AB  - Reactive oxygen species (ROS) are involved in a number of disease states where
      they are believed to be responsible for cellular damage. In this study we
      examined the effect of ROS generation on polyamine catabolism. Treatment of human
      breast cancer cells with either H2O2 or hyperoxia increased the activity of
      spermidine/spermine N1-acetyltransferase (SSAT). These increases occurred before
      any significant signs of cellular injury. Agents known to decrease the production
      of reactive oxygen species such as dimethylthiourea and o-phenanthroline
      prevented the increase in SSAT activity indicating ROS involvement in the
      induction process. These results suggest that induction of SSAT may be a
      protective response to oxidative stress in mammalian cells facilitating removal
      of polyamines from the cell to prevent their toxic accumulation.

PMID- 9605437
TI  - Flavonoid-induced ability of minimally modified low-density lipoproteins to
      support lymphocyte proliferation.
AB  - Low-density lipoprotein (LDL) peroxidation appears to be involved in
      atherogenesis. We studied the ability of minimally modified LDL (MM-LDL) to be
      used by proliferating lymphocytes and the effects of antioxidant flavonoids on
      this lipoprotein. MM-LDL were obtained by storing LDL at 4 degrees for 1 month,
      which resulted in a decrease in lipophilic antioxidants and an increased
      susceptibility to oxidation when incubated with cells. MM-LDL were not cytotoxic;
      however, in cells treated with lovastatin that require cholesterol for cell
      growth, they were much less efficient than fresh LDL in sustaining proliferation
      as determined by [3H]thymidine incorporation into DNA. Pure quercetin and grape
      derived beverages restored proliferation in the presence of MM-LDL and prevented
      the apoptosis otherwise induced by lovastatin. These effects of flavonoids
      correlated with their activity in inhibiting LDL peroxidation. The results
      demonstrate that potent antioxidants, such as flavonoids, protect MM-LDL from
      lipoperoxidation and preserve their ability to efficiently deliver cholesterol to
      cells.

PMID- 9605438
TI  - The cyclosporine A-induced decrease in rat renal calbindin-D28kDa protein as a
      consequence of a decrease in its mRNA.
AB  - Cyclosporine A (CsA) is a potent immunosuppressant with the drawback of renal
      side-effects. We recently reported that relatively high doses of CsA markedly
      decreased the calcium-binding protein calbindin-D28kDa in kidneys of male Wistar
      rats, and showed that this decrease could be associated with some of the drug
      induced adverse renal effects. To investigate the events leading to this
      decrease, the calbindin-D28kDa mRNA level in kidneys of rats treated with 15 or
      50 mg/kg/day CsA for 12 days was analysed by reverse transcription followed by
      polymerase chain reaction. At both doses, a marked dose-dependent decrease in the
      calbindin-D28kDa mRNA level was found, one very similar to the decrease measured
      in the calbindin-D28kDa protein abundance. Thus, the CsA-mediated down-regulation
      of the renal calbindin-D28kDa protein is most likely the result of a decrease in
      the calbindin-D28kDa mRNA level.

PMID- 9605439
TI  - Gene amplification and increased expression of the reduced folate carrier in
      transport elevated K562 cells.
AB  - The molecular bases for the 6-fold elevated methotrexate transport capacity of
      K562.4CF cells (Matherly et al., Cancer Res. 51: 3420-3426, 1991) were studied
      with reduced folate carrier (RFC) cDNA, genomic, and antibody probes. Southern
      analysis showed that RFC gene copies were increased (approximately 4- to 5-fold)
      in K562.4CF over wild-type K562 cells. Fluorescence in situ hybridization using a
      genomic RFC probe confirmed the localization of the RFC gene to the q-arm of
      chromosome 21. In K562.4CF cells, the frequent loss of a normal copy of
      chromosome 21 (61% of metaphases) was accompanied by RFC gene amplification and
      translocations of amplified RFC gene fragments to several (2 to 6) different
      chromosomal loci not seen in wild-type cells. Particularly intense RFC signals
      were mapped to homogeneously staining regions in chromosomes 2 and 15. Increased
      RFC gene copies were accompanied by a similar increase in the major 3.1 kb RFC
      transcript by northern blotting and an approximately 7-fold elevated level of the
      broadly migrating (80-95 kDa) RFC protein on a western blot probed with an RFC C
      terminal peptide antibody. These results demonstrate that selection of cells with
      a growth-limiting concentration of reduced folates (0.4 nM of leucovorin) is
      sufficient to promote chromosomal aberrations, including gene amplification and
      translocations that result in increased RFC expression and folate transport.

PMID- 9605440
TI  - Breech delivery: the value of X-ray pelvimetry.
AB  - OBJECTIVE: The study was conducted to compare maternal and neonatal outcome of
      two groups of nulliparae with breech presentations, who were selected for vaginal
      delivery by protocols differing only in their use of X-ray pelvimetry. STUDY
      DESIGN: We reviewed all term singleton breech deliveries of nulliparous patients
      who were eligible for vaginal trial of labour in our Centre between 1992 and
      1994. In Group A (n=85) X-ray pelvimetry was performed, and in Group B (n=70) it
      was not. Obstetric management was otherwise similar. Admission to the two
      departments was on alternate days. RESULTS: The rate of caesarean section was
      similar in both groups (Group A, 36.4% vs. Group B, 42.8%; P>0.05), however, the
      indications for caesarean section differed. Neonatal outcome was similar in both
      groups. Maternal febrile morbidity was higher in Group B patients, especially
      those who underwent caesarean section after a trial of labour. CONCLUSION: X-ray
      pelvimetry in nulliparae with breech presentation is associated with reduced
      maternal febrile morbidity, but does not improve neonatal outcome.

PMID- 9605441
TI  - Elevated interleukin-8 concentrations in amniotic fluid of mothers whose neonates
      subsequently develop bronchopulmonary dysplasia.
AB  - OBJECTIVE: To determine if an intrauterine sub-clinical inflammatory process is a
      risk factor for the development of bronchopulmonary dysplasia. METHODS: A cohort
      study was conducted in patients who met the following criteria: (1) Singleton
      gestation; (2) preterm labor or preterm premature rupture of the membranes; (3)
      amniocentesis for microbiologic studies of the amniotic fluid and (4) delivery
      between 24 and 28 weeks of gestation. Bronchopulmonary dysplasia was defined as
      the need for supplemental oxygen for 28 days or longer after birth, associated
      with compatible chest radiographic findings. Amniotic fluid interleukin-8, was
      measured using a specific immunoassay. Logistic regression analysis and bootstrap
      procedure were used for statistical purposes. RESULTS: Forty-seven patients met
      the inclusion criteria for this study. Among these patients, the prevalence of
      bronchopulmonary dysplasia was 23.4% (11/47). Amniotic fluid culture was positive
      in 21 out of 47 (44.7%) patients. Median (range) amniotic fluid interleukin-8
      concentration was higher in patients whose neonates subsequently developed
      bronchopulmonary dysplasia than in those who did not (17 [9.8-583.7] ng ml(-1)
      versus 9.6 [0.91-744] ng ml(-1), P=0.057). An amniotic fluid IL-8 level greater
      than 11.5 ng ml(-1) was far more common in mothers whose fetuses went on to
      develop bronchopulmonary dysplasia than in those who did not (10/11 [90.9%]
      versus 17/36 [47%]; P=0.01). This relationship remained significant even after
      correcting for the effect of gestational age and birthweight (Odds ratio: 11.9;
      P<0.05). CONCLUSION: Sub-clinical intrauterine inflammation is a risk factor for
      the subsequent development of bronchopulmonary dysplasia. We propose that in
      utero aspiration of fluid with high concentration of pro-inflammatory mediators
      may contribute to the lung injury responsible for the development of
      bronchopulmonary dysplasia.

PMID- 9605442
TI  - Study of the variations of the cesarean sections rate in the Rhone-Alpes region
      (France): effect of women and maternity service characteristics.
AB  - OBJECTIVE: To analyze the variations of the rate of prophylactic cesarean
      sections and cesarean sections during labor according to the women's and
      maternity services' characteristics. STUDY DESIGN: The study population was a
      sample of 8470 women having delivered in one of the 86 maternity services of the
      Rhone-Alpes region (France) in 1990. The women's characteristics were risk
      factors for pregnancy or delivery. The maternity services' characteristics
      included those describing the service structure and the mode of recruitment. For
      the statistical analysis we used a two-level logistic model. RESULTS: After
      taking into account the women's characteristics, there remained a variation
      between the maternity services. This variation was in part explained by the type
      of recruitment of the maternity service. When the proportion of women with a
      previous cesarean section or a dystocia increased in the maternity service the
      cesarean sections rate decreased in women presenting similar characteristics.
      CONCLUSION: Thus, the maternity services which receive many "at risk" women tend
      to have higher cesarean section rates than the others. However, in comparison
      with women presenting similar characteristics, these same maternity services tend
      to perform fewer cesarean sections.

PMID- 9605443
TI  - Perinatal outcome of singleton term breech deliveries.
AB  - OBJECTIVE: To assess neonatal morbidity and mortality in singleton term infants
      delivered in breech presentation and to find a possible correlation between
      outcome and mode of delivery. STUDY DESIGN: Case study of 306 singleton, term (37
      42 weeks), breech deliveries, that took place between 1989 and 1994 in one
      perinatal centre. RESULTS: 170 infants were delivered vaginally, 72 by elective
      and 64 by secondary cesarean section. Even after application of strict selection
      criteria -- i.e. prior pelvic assessment by staff obstetricians, an estimated
      birth weight of 2500-4000 g -- and with staff supervision, vaginal delivery
      turned out to be associated with a significantly higher incidence of low
      umbilical artery pH values and neonatal care unit admissions as compared to
      elective cesarean section. Five infants suffered mechanical trauma. One neonatal
      death occurred in the vaginal delivery group. CONCLUSION: The results of this
      retrospective study of 306 singleton term breech deliveries imply that even after
      strict selection of patients, vaginal delivery is associated with increased
      neonatal morbidity in comparison to elective cesarean section.

PMID- 9605444
TI  - The prediction of preeclampsia: reassessment of clinical value of increased
      plasma levels of fibronectin.
AB  - OBJECTIVE: To determine whether assessment of plasma fibronectin in primigravidae
      could predict the pregnant women expected to become preeclamptic. METHODS: We
      performed a prospective blinded analysis of 156 apparently normotensive
      primigravidae in an outpatient clinic. Blood samples were taken at 6 week
      intervals from the 18th week and immediately after delivery or at the onset of
      preeclampsia. Plasma fibronectin was evaluated by ELISA. Evolution with
      gestational age was studied using regression curves. RESULTS: We had 148 normal
      primigravidae (592 determinations). In three women, increased fibronectin
      anticipated preeclampsia by 3-4 weeks. Five women showed high levels only at the
      onset of preeclampsia. Sensitivity, specificity, positive and negative predictive
      values of increased fibronectin levels were 37.5% (95% CI=3.3-71.7), 96.6% (95%
      CI=93.7-99.6), 37.5% (95% CI=3.3-71.7) and 96.6% (95% CI=93.7-99.6),
      respectively. CONCLUSIONS: This study shows that plasma fibronectin levels could
      represent a specific marker for preeclampsia. Its sensitivity has to be improved
      but its high negative predictive value strongly argues against the development of
      preeclampsia within the next 4 weeks after the blood sampling.

PMID- 9605445
TI  - Routine revision of uterine scar after cesarean section: has it ever been
      necessary?
AB  - Although a trial of labor after cesarean section (VBAC) is successful and
      relatively safe, few studies have directly addressed the necessity of routine
      transcervical revision of uterine scar after prior cesarean section. We performed
      a longitudinal study of 3469 women who had VBAC. In all patients, uterine scar
      integrity was examined immediately after placental expulsion. The detection rate
      of uterine scar dehiscence or rupture was 0.23% (8/3469). Only one woman with
      complete uterine rupture needed immediate laparotomy for severe hemorrhage. Out
      of seven patients (0.2%), who had evidence of uterine dehiscence, three underwent
      explorative laparotomy. In conclusion, the potential benefit of routine
      examination of uterine scar after VBAC is doubtful. Transcervical revision should
      be performed only in symptomatic patients.

PMID- 9605446
TI  - Immunomodulation induced by intrauterine transfusions.
AB  - Intrauterine transfusion (IUT) therapy offers a unique model to study the
      immunological consequences of fetal exposure to donor alloantigens. IUT can
      result in immediate and short effects. Directly after IUT a relative leukocytosis
      was observed, which was evenly distributed among the different leukocyte subsets.
      After the course of IUT treatment a memory response against donor antigens was
      generated. This was also reflected by an increase in CD3/CD45RO+ T-cells and
      modulation of T cell receptor Vbeta (TCRBV) repertoire. However, a long term
      clinical follow-up study on IUT patients who received this treatment in the
      1960's revealed no evidence of serious side effects. Furthermore, persistence of
      donor leukocytes and in vitro immunomodulation could not be observed.

PMID- 9605447
TI  - Aspects of food and fluid intake during labour. Policies of midwives and
      obstetricians in The Netherlands.
AB  - OBJECTIVE: This study outlines the current policies on food and fluid intake
      during labour in The Netherlands and discusses the pro's and con's of food
      restriction. STUDY DESIGN: 50 midwives and 30 obstetricians were asked about
      their actual policy on food and fluid-intake during labour. RESULTS: A
      restrictive policy during normal labour is followed by 20% of the midwives and
      14% of the obstetricians. About 75% leaves the decision on food and fluid-intake
      to the women themselves. CONCLUSIONS: Despite the non-restrictive policy in The
      Netherlands, the mortality due to the Mendelson-syndrome is not higher than in
      countries where a restrictive policy is followed. During normal labour there are
      no conclusive reasons for food or fluid-restriction. From a metabolic point of
      view it is hypothesized that the intake of energy-rich substrates may have a
      positive influence on labour progression. Further study on the subject seems
      indicated.

PMID- 9605448
TI  - Fetal plasma levels of circulating endothelial cell adhesion molecules in normal
      and preeclamptic pregnancies.
AB  - OBJECTIVE: Circulating levels of endothelial cell adhesion molecules are elevated
      in women with preeclampsia. The aim of the present study was to determine levels
      of these molecules in the fetal circulation of normal pregnancies and pregnancies
      complicated by preeclampsia. STUDY DESIGN: Fetal plasma samples from the
      umbilical vein and peripheral maternal plasma and serum sample were collected at
      delivery from women with preeclampsia and women with normal pregnancy. Women with
      non-proteinuric pregnancy-induced hypertension (PIH) were excluded from the
      study. A sandwich ELISA technique was employed to quantitate concentrations of
      soluble ICAM-1 (CD54), VCAM-1 (CD106), and E-selectin (CD62E). RESULTS: The
      normal values of soluble endothelial cell adhesion molecules in the fetal
      circulation were determined as 162+/-45 ng/ml for ICAM-1, 1612+/-582 ng/ml for
      VCAM-1, and 154+/-58 ng/ml for E-selectin. They were found to markedly differ
      from the corresponding normal values in the maternal circulation (sICAM-1: 247+/
      65 ng/ml; sVCAM-1: 715+/-170 ng/ml; sE-selectin: 34+/-14 ng/ml). The
      concentrations of sICAM-1, sVCAM-1, and sE-selectin were significantly elevated
      in women with preeclampsia compared to healthy control pregnant women. In
      contrast, there was no difference in the circulating fetal concentrations of
      these molecules between normal pregnancies and pregnancies complicated by
      preeclampsia. CONCLUSIONS: Normal values of sICAM-1, sVCAM-1, and sE-selectin in
      fetal circulation are markedly different from the values obtained for healthy
      adults. Plasma concentrations of these molecules are elevated in women with
      preeclampsia but not in the fetal circulation of preeclamptic pregnancies
      suggesting that based on the analysis of soluble adhesion molecules the fetal
      circulation may not be affected by the factor(s) that lead to disturbed
      endothelial cell function in women with preeclampsia.

PMID- 9605449
TI  - The usefulness of a weight gain spurt to identify women who will develop
      preeclampsia.
AB  - OBJECTIVE: The usefulness of adaptive centiles for weight gain as well as sudden
      weight gain spurts in identifying women who will develop preeclampsia was
      assessed. METHODS: A study sample of 99 women who developed preeclampsia and a
      control sample of 675 women with normal pregnancies, were randomly selected.
      Weight gain spurts were identified by the upper bound of adaptive maternal weight
      centiles. Average changes in weight between successive clinic visits were also
      assessed. RESULTS: Weight gain exceeding the 90th percentile of the adaptive
      centiles resulted in estimated sensitivity and specificity of 52% and 66% and
      weight gain >0.9 kg per week between visits in 76% and 29% respectively. Of women
      who would develop preeclampsia identified by the adaptive chart, 62.0% exhibited
      abnormal weight gain prior to the onset of abnormal clinical findings.
      CONCLUSIONS: A sudden weight gain spurt is a far from reliable sign of impending
      preeclampsia. This reason for weighing women at antenatal visits appears to be
      unfounded.

PMID- 9605450
TI  - Placental anatomy, fetal demise and therapeutic intervention in monochorionic
      twins and the transfusion syndrome: new hypotheses.
AB  - OBJECTIVE: Monochorionic twins with circulatory sharing have an incompletely
      understood response to acute hemodynamic events. We relate placental vascular
      anatomy with, first, the response to (a) acute fetal demise and (b) laser
      interrupted placental anastomoses and, second, the efficacy of current and
      possibly future therapeutic interventions in twin-twin transfusion syndrome.
      DESIGN: Hemodynamic response to acute fetal demise and laser interrupted
      anastomoses is analysed using the model previously developed for monochorionic
      twins. Efficacy of therapeutic interventions in twin-twin transfusion syndrome is
      analysed by combining the estimated incidence of placental anastomotic patterns
      with three previously proposed pathophysiologic mechanisms. RESULTS: Fetal demise
      may cause sequelae for the co-twin in all anastomotic patterns except
      unidirectional arteriovenous and single venovenous anastomoses which are
      predicted to be hemodynamically harmless. In twin-twin transfusion syndrome,
      laser interruption of all anastomoses mitigates further transfusion. This is of
      benefit for the twins in equally but not in unequally shared placentas. Analysis
      predicts that approximately 75% fetal survival could be achieved interrupting
      only arteriovenous anastomoses. Amniocentesis may only prolong pregnancies that
      lack progressively increasing discordance, assuming that placental anastomoses
      remain patent following polyhydramnios. This proposed mechanism of action
      predicts current therapeutic efficacy accurately and could explain the
      significantly higher reported serious morbidity compared with laser (15/81 = 19+/
      5% versus 4/146=3%, P=0.00004). However, if therapeutic interventions could match
      the syndrome's individual placental anatomy, the analysis suggests approximately
      10-15% laser related mortality (premature rupture of membranes) and <3% severe
      morbidity could possibly become achievable goals. CONCLUSION: Our predictions
      allow clinical testing. This information may contribute to an improved management
      of monochorionic twins.

PMID- 9605451
TI  - Emergency cervical cerclage: a study between duration of cerclage in situ with
      gestation at cerclage, herniation of forewater, and cervical dilatation at
      presentation.
AB  - OBJECTIVE: To investigate the effectiveness of emergency cerclage in prolonging
      pregnancy and its effect on pregnancy outcome in patients with cervical
      incompetence. STUDY DESIGN: Retrospective review of patients who had emergency
      cervical cerclage performed for cervical incompetence. 19 patients between 16 and
      30 weeks' gestation with (1) cervical effacement, (2) cervical dilatation of at
      least 1 cm, (3) herniation of intact fetal membranes through the cervical os, (4)
      absence of established labor, and (5) absence of clinical evidence of infection
      were studied. The duration of cerclage in situ, gestation at delivery and birth
      weight were analyzed. RESULTS: The mean duration of cerclage in situ was 47.5+/
      48.6 days. The mean gestation at delivery was 30.5+/-6.6 weeks and the mean birth
      weight was 1730+/-1105 grams. The duration of cerclage in situ was significantly
      longer when the procedure was performed at or before 20 weeks' gestation (Mann
      Whitney U test, P<0.02), or when there had been no herniation of forewater (HFW)
      at the time of presentation (Mann-Whitney U test, P<0.05). CONCLUSIONS: Gestation
      at cerclage and the presence of herniation of forewater (HFW) at presentation of
      cervical incompetence significantly affect the duration of emergency cerclage in
      situ.

PMID- 9605452
TI  - Reconsidering menorrhagia in gynecological practice. Is a 30-year-old definition
      still valid?
AB  - OBJECTIVE: To determine whether the 30-year-old definition of menorrhagia
      (menstrual blood loss of 80 ml or more) is still valid in gynecological practice
      today. STUDY DESIGN: Of 313 Dutch women, recruited from gynecological practice,
      the menstrual blood loss of one bleeding episode was objectively measured and
      related to the women's hemoglobin concentrations as well as their serum ferritin
      levels. Also, the 95th percentile of menstrual blood loss was calculated of women
      with normal hematological parameters, representing an upper normal limit.
      RESULTS: The percentage of women suffering from anemia exceeded the overall mean
      above 120 ml of menstrual blood loss. The 95th percentile of menstrual blood loss
      of women with normal hemoglobin concentrations (12 g/dl or above) and with normal
      serum ferritin levels (16 microg/l or above) was 115 ml. CONCLUSION: The risk of
      developing anemia from heavy menstrual bleeding is substantially increased at a
      menstrual blood loss level of 120 ml, and not, like the current definition of
      menorrhagia suggests, at 80 ml.

PMID- 9605453
TI  - Histocompatibility antigen studies in women with recurrent miscarriages and
      Mullerian uterine anomalies.
AB  - OBJECTIVE: To determine whether the HLA alleles DR1, DR3, DR4 and DR10 which have
      been suggested to be risk markers for unexplained recurrent miscarriages also
      play a part in women with recurrent miscarriages with Mullerian uterine fusion
      anomalies. STUDY DESIGN: HLA-DR typing was undertaken in 28 women with recurrent
      miscarriage who had been surgically treated for Mullerian anomalies and in 360
      controls. In the study group, outcome of pregnancies after surgery was correlated
      to the results of the HLA typing. RESULTS: In the study group, 61% were positive
      for HLA-DR1, -DR3, -DR4 or -DR10 compared with 65% of the controls (not
      significantly different). Among patients positive for these HLA risk markers, 64%
      of the pregnancies after surgery miscarried compared with 13% in those negative
      (P<0.005, RR for miscarriage=4.8, 95% CI= 1.3-18.0). CONCLUSION: The proposed
      risk HLA markers for unexplained recurrent miscarriage also seem to display a
      negative impact on pregnancy outcome in patients with recurrent miscarriages with
      Mullerian uterine anomalies.

PMID- 9605454
TI  - Drastic elevation of serum CA125, CA72-4 and CA19-9 levels during menses in a
      patient with probable endometriosis.
AB  - Levels of CA125, CA72-4 and CA19-9, serum markers for ovarian cancer, were
      measured throughout menstrual cycles in a patient with probable pelvic
      endometriosis. The patient had CA125 levels >1000 U ml(-1), CA72-4>10 U ml(-1)
      and CA19-9>150 U ml(-1) during but not after menses (P<0.01). In luteal phase and
      premenstrual phase, the levels of these markers seemed to return normal ranges,
      although CA125 remained over the upper normal limit. Knowledge that a
      physiological elevation of these markers may occur during menses might avoid
      misinterpretation.

PMID- 9605455
TI  - Evaluation of cervical dysplasia treatment by large loop excision of the
      transformation zone (LLETZ). Does completeness of excision determine outcome?
AB  - OBJECTIVES: To evaluate the therapeutic and diagnostic potential of large loop
      excision of the transformation zone (LLETZ) in the management of cervical
      dysplasia (CD) when colposcopy is satisfactory; to determine if there is a
      relationship between completeness of excision and outcome. STUDY DESIGN: Ninety
      loop diathermies performed in the management of CD were studied prospectively.
      RESULTS: Eighty (88.89%) were indicated due to a high grade CD, 7 (7.78%) due to
      a low grade CD and 3 LLETZ (3.35%) due to a cytology-biopsy discordance. The
      margins were free of disease on 69 occasions (76.67%); on 15 (16.67%) the margins
      were affected by the disease and on 6 (6.67%) they were not evaluable. Using the
      Kaplan-Meier approach to survival analysis, the cumulative probability of
      continuing free of disease at the end of our study (36 months) was 0.89. In the
      margins free of disease group, patients stayed free of disease for an average of
      32.98 months, and the cumulative probability of continuing free of disease at 36
      months was 0.97. In the affected-margins group, patients stayed free of disease
      for an average of 20.91 months and the cumulative probability of continuing free
      of disease at 36 months dropped to 0.70. In the unevaluable-margins group,
      patients stayed free of disease for an average of 19.50 months and the cumulative
      probability of continuing free of disease at 36 months dropped still further to
      0.67. Applying the Mantel-Cox Log-Rank Test we obtained differences among these
      three groups that are statistically significant (P<0.005). CONCLUSIONS: LLETZ
      could be considered the treatment of choice for CD when colposcopy is
      satisfactory, as it is effective, simple, fast, inexpensive, unaggressive, and of
      low morbidity. It also permits adequate pathology reporting. When a pathology
      report states that the margins of the specimen are not free of disease or are not
      evaluable, special caution in follow-up may be warranted.

PMID- 9605456
TI  - Complete remission of brain metastases from ovarian carcinoma with carboplatin.
AB  - Central nervous system involvement by epithelial ovarian carcinoma is rare. We
      report the case of a 49 year old woman with stage IV serous carcinoma of the
      ovary who developed multiple cerebral and cerebellar metastases 7 months after
      achieving complete response to platin-based chemotherapy. Eight courses of
      carboplatin (400 mg/m2) were administered and after the second cycle complete
      remission of the brain deposits occured. The treatment afforded rapid subjective
      and objective relief and was associated with a good quality of life. Abdominal
      recurrent disease was diagnosed 22 months after treatment for brain involvement.
      Paltin-based chemotherapy was reinstated, but the patient died from progressive
      adbominal disease without any sign of cerebral involvement and any neurological
      symptomatology. Carboplatin should be considered for the treatment of ovarian
      carcinoma metastatic to the brain.

PMID- 9605457
TI  - Ovarian mixed germ cell tumor comprising polyembryoma and choriocarcinoma.
AB  - Both polyembryoma and choriocarcinoma are exceedingly rare germ cell tumors of
      the ovary, and a mixed germ cell tumor containing both neoplastic components has
      not been described. Recently we encountered such a case.

PMID- 9605458
TI  - The apparent late half-life of human chorionic gonadotropin (hCG) after surgical
      treatment for ectopic pregnancy. A new approach to diagnose persistent
      trophoblastic activity.
AB  - OBJECTIVE: The disappearance kinetic of human chorionic gonadotropin (hCG)
      follows a biexponential decay with a rapid initial fall followed later by a slow
      disappearance. This kinetic is characterised by two half-lives: an early and a
      late. The objective of this study was to determine if and which half-life could
      be used clinically to detect persistent trophoblast after conservative surgery in
      patients with ectopic pregnancy. DESIGN: Retrospective analysis of patients
      having undergone salpingostomy by laparoscopy for an ectopic tubal pregnancy
      between January 1990 and October 1993. SETTING: Gynaecology Department of an
      University Hospital. PATIENTS: 104 women with diagnosed tubal ectopic pregnancy
      were treated by salpingostomy performed under laparoscopy. In seven cases,
      persistent trophoblast was diagnosed on the basis of plateauing or increasing
      peripheral hCG values. MAIN RESULTS: From the individual disappearance curves of
      hCG we calculated the early half-life (early T0.5, from samples obtained between
      0 and 48 h postsurgery) and the late half-life (late T0.5, from samples obtained
      between 2 and 7 days postsurgery). Late T0.5 but not early T0.5 were
      significantly (P<0.0001 and P=0.416 respectively) longer in women (n =7) in whom
      a persistent trophoblast was diagnosed. Early T0.5 was dependant on the
      preoperative value of hCG, whereas late T0.5 was independent. We propose to use
      late T0.5 as a parameter to follow ectopic pregnancies after treatment.

PMID- 9605459
TI  - A computer based, temperature controlled bipolar electrocoagulation system: II.
      Optimal temperature and coagulation time.
AB  - OBJECTIVE: A computer based, temperature controlled bipolar coagulation system
      has been developed. This system was evaluated for its efficiency on
      electrocoagulation of rabbit uterine horns at a low temperature. STUDY DESIGN: In
      purpose to find an optimal setting, rabbit uterine horns were coagulated at
      various temperature and time. They were examined histologically and
      histochemically up to six weeks after coagulation. RESULTS: Electrocoagulation at
      90 degrees C for 30 s induced a total occlusion of the lumen when examined six
      weeks later. CONCLUSION: This coagulation system with low temperature is
      sufficient for a total occlusion of uterine lumen in the rabbit.

PMID- 9605461
TI  - Laparoscopic adnexal preservation in a patient with complete torsion--a case
      report.
AB  - OBJECTIVE: Laparoscopic adnexal preservation in a patient with complete torsion.
      STUDY DESIGN: Laparoscopy was performed in a 20-year-old nulliparous patient with
      a 24-h history of lower abdominal pain. RESULTS: Torsion of the left adnexa was
      diagnosed and detorsion was performed. After detorsion the patient reported
      complete resolution of pain. At second look laparoscopy blood supply of the left
      adnexa was completely normalized and a cystadenofibroma was excised with
      preservation of the ovary. CONCLUSIONS: Complete torsion of adnexa associated
      with edema and ischemia can be treated by laparoscopic detorsion.

PMID- 9605460
TI  - Hyaluronic acid plus heparin for improved efficacy in prevention of adhesion
      formation in rat uterine horn model.
AB  - OBJECTIVE: To determine the effectiveness of hyaluronic acid (HA) and heparin
      [unfractioned heparin (UH) or low molecular weight heparin (LMWH)] combination in
      reducing adhesion formation in a rat uterine horn model. STUDY DESIGN:
      Prospective, randomized, comparative study in a rat model was done in Surgical
      Research Laboratory, Erciyes University. A standard lesion was created by
      unipolar electrocautery in 120 uterine horns of total 60 female Wistar-Albino
      rats. Animals were then randomly assigned into four groups, each consisting of 15
      animals: (1) control, no adjuvant given; (2) HA, 1 ml of 0.4% solution given onto
      each horn preoperatively; (3) HA, 1 ml of 0.4% solution given preoperatively plus
      1 ml of UH given postoperatively; (4) HA, 1 ml of 0.4% solution given before
      injury plus 1 ml of LMWH given after injury. A second-look laparotomy was
      performed two weeks after surgery. The number of horns with adhesion was
      determined and a scoring system applied. RESULT(S): The number of horns without
      adhesion formation was significantly higher in HA plus UH (P<0.05) and HA plus
      LMWH (P<0.01) groups compared to control group. The extent, severity and total
      scores of adhesion formation were also found to be significantly reduced in other
      groups when compared to control group. Combination of HA plus UH and HA plus LMWH
      significantly reduced all adhesion scores compared to HA alone. But a direct
      comparison of the ability of HA plus UH versus HA plus LMWH in reducing adhesion
      scores in the rat uterine horn yielded an insignificant difference. CONCLUSION:
      Administration of HA before injury followed by UH or LMWH given after injury has
      been documented to improve the efficacy of HA alone in reducing adhesion
      formation.

PMID- 9605462
TI  - Is baby too warm? The use of infant clothing, bedding and home heating in
      Victoria, Australia.
AB  - Overheating of infants has been associated with a raised risk for sudden infant
      death syndrome (SIDS). Data on the use of heating, bedding and clothing and other
      measures affecting the thermal environment of 4 week old infants were collected
      at a home interview for infants of women born in Australia (Anglo-Celtic
      background), in Southern Europe, in Asia and of women who had a planned out-of
      hospital birth. These groups have different risks of SIDS not explained by the
      classic social and perinatal risk factors nor associated with the currently
      promoted 'new' risk factors. Thermal insulation of the infant's bedding and
      clothing and excess thermal insulation (for any observed room temperature) were
      calculated. Bed sharing differed significantly between the groups as did the use
      of a sheepskin, tucking in firmly, the closing of doors and windows and the use
      of heating in the infant's room. After stratifying by bed sharing practice and
      season of interview, it was found that bed sharing infants had more thermal
      insulation than those sleeping alone irrespective of season of interview. Infants
      sleeping alone in the Asian-born and Southern European-born groups were kept
      warmer than infants in the other two groups. Cultural factors appear to affect
      the thermal environment in which infants are raised. Some bed sharing infants in
      all four groups were inappropriately warm, particularly in colder weather, but
      this was more likely in the Asian-born (low risk) group than in the home birth
      (high risk) group. These results do not explain the differences in SIDS incidence
      between the groups.

PMID- 9605463
TI  - The relationship of fetal serum markers of bone metabolism to gestational age.
AB  - The aim of this study is to determine the pattern of fetal bone metabolism by
      measuring umbilical cord levels of carboxy terminal pro-peptide of type I pro
      collagen (PICP) and cross-linked carboxyterminal telopeptide of type I collagen
      (ICTP). PICP and ICTP directly monitors the rate of bone formation and
      resorption, respectively. Samples were obtained at the time of delivery from 20
      healthy women with pregnancies at different gestations. There is a significant
      inverse correlation between fetal levels of PICP and ICTP, and gestation (PICP r=
      0.504, p=0.023; ICTP r=-0.713, p < 0.001), and between ICTP and birth weight (r=
      0.466, p=0.038), but the birth weight effect is a function of gestational age.
      Therefore, both bone formation and resorption decrease with gestational age.
      Although contrary to the suggestion that fetal ossification increases at the end
      of pregnancy, such changes may be due to the shift from growth to maintenance.

PMID- 9605464
TI  - Developmental characteristics in sustained fetal tachycardia in 30 to 41 weeks of
      gestation.
AB  - The aim of the present study is to reveal gestational age-related changes in
      sustained foetal tachycardia (SFT). 24 h fetal heart rate (FHR) recordings were
      made on 102 normal pregnant women in 30-41 weeks of gestation. SFT was defined as
      an increase for 20 or more beats per minute from the FHR-baseline persisting for
      more than 20 min. In the results, SFTs in 38-39 weeks started during night-time
      (1900-0700) more frequently than during day-time (0700-1900) (P < 0.01, by chi
      square test). The rate and duration were 0% and 0 min in 30-31 weeks of
      gestation, and increased to 85% and 114 min in 40-41 weeks, respectively. Two
      critical points were detected by a piecewise linear regression analysis: in the
      rate between 34-35 weeks and 36-37 weeks, and in the duration between 38-39 to 40
      41 weeks. We conclude that gestational age-related changes in SFT depend on the
      developmental stages.

PMID- 9605465
TI  - Infant temperament and child-rearing stress: birth order influences.
AB  - The relationship between an infant's temperamental difficulty and the mother's
      child-rearing stress was investigated in a sample of 128 children. Children's
      temperament was assessed by the Revised Infant Temperament Questionnaire (RITQ)
      at 6-7 months, and by the Toddler Temperament Scale (TTS) at 18 months. The
      mothers' child-rearing stress was assessed by a self-report questionnaire. At the
      children's age of 18 months, mothers of difficult children reported higher child
      rearing stress than mothers of easy children. Although difference in the level of
      child-rearing stress reflecting birth order was not evident at either 6-7 months
      or 18 months, the proportion of child-rearing stress which could be explained by
      the children's temperament was highest for mothers of first-borns when their
      children were 18 months old.

PMID- 9605466
TI  - Computer-assisted analysis of fetal movements in intrauterine growth retardation
      (IUGR).
AB  - A quantitative analysis of various fetal activities (mouth, eye and gross body
      movements) was made in 10 IUGR human fetuses. The aim of the study was to see
      whether IUGR fetuses move differently to normal fetuses. Each real-time
      ultrasound recording lasted 1 h and the analysis of various activities was
      carried out during replay of video recordings by means of a specially designed
      computer program. The following aspects have been investigated: (1) incidence,
      duration and interval for each of the fetal activities described; (2) the
      relationship between incidence, duration and interval for each single activity;
      (3) the correlations between the different activities. The results were compared
      with a group of 10 fetuses from normal pregnancies. On quantitative evaluation no
      clear effects due to uncomplicated IUGR could be detected except for median
      duration of eye movements, which turned out to be longer in the IUGR group. The
      evaluation of correlations between the characteristics (incidence, duration and
      interval) of each activity showed a positive correlation between incidence and
      duration of mouthing movements in the IUGR group, not found in the normal group.
      The study of the correlation between different fetal activities has shown an
      inverse correlation between mouthing and other activities in the normal fetuses,
      not found in the IUGR group. We conclude that in mildly affected fetuses with no
      evidence of hypoxia, there are no quantitative differences compared to normal
      fetuses in terms of the motility studied. The only differences found were in
      relation to the performance of such activities and they could reflect a
      dysfunction of the central nervous system resulting from a metabolic disturbance.

PMID- 9605467
TI  - Cerebral metabolic response to hypoglycemia in severe intrauterine growth
      retarded rat pups.
AB  - This study was to examine the effects of hypoglycemia on the brain metabolism of
      severe intrauterine growth retardation (IUGR) rat pups. IUGR pups were produced
      by ligating one of the uterine arteries of the dams. The pups on the opposite
      uterine horn were used as the control. They were delivered by cesarean section on
      day 21 and received regular insulin 5 units/kg or equivalent volume of normal
      saline at 40 min of age. The plasma glucose, lactate, blood gas values and brain
      glucose, lactate, and ATP contents were determined at 5 and 100 min of age. The
      IUGR pups had higher plasma and brain lactate concentrations than the control
      throughout the study period. They had lower plasma glucose, oxygen and pH values,
      brain glucose and ATP contents than control at 5 min of age. Despite insulin
      induced hypoglycemia, brain ATP contents of the IUGR recovered to normal levels
      at 100 min of age when the oxygenation and pH improved. These data indicate that
      the brain energy metabolism of IUGR rat pups was suppressed by asphyxia and
      hypoglycemia. However, even in the continuing presence of hypoglycemia, brain
      energy metabolism returned to normal. The recovery is probably related to better
      oxygenation and utilization of alternative energy fuels, such as lactate.

PMID- 9605468
TI  - Free amino acid distribution inside the first trimester human gestational sac.
AB  - The trophoblast functions of nutrient transport and protein synthesis generate
      high concentrations of amino acids in the placenta and in fetal blood during the
      second half of pregnancy, but little is known about these metabolic processes in
      embryonic and early fetal periods. The aim of this study is to compare the
      distribution of amino acids inside the first trimester gestational sac. Free
      amino acid concentrations were measured in homogenates of placental villi, in
      samples of coelomic and amniotic fluid, and in the maternal serum from 17 normal
      pregnancies between 7 and 11 weeks of gestation. Significant positive
      relationships between maternal serum and placental tissue were found for 10 amino
      acids, indicating that active amino acid transport and accumulation by the human
      syncytiotrophoblast occurs as early as 7 weeks of gestation. The transplacental
      flux of most amino acid transport from maternal blood to the exocoelomic cavity
      was against a concentration gradient. The highest placental amino acid
      concentrations were found for taurine, glutamic acid, glycine and alanine. The
      amniotic fluid contained lower mean concentration of all amino acids than
      coelomic fluid and maternal serum. The concentration distribution of individual
      amino acids in coelomic and amniotic fluid were related indicating a passive
      transfer through the amniotic membrane. A coelomic-maternal gradient was observed
      in 19 out of 24 amino acids measured and positive correlations were found between
      maternal serum and coelomic fluid for concentrations of alpha-aminobutyric acid,
      tyrosine and histidine, suggesting that these amino acids are only partially
      retained and/or transferred more rapidly by the early placenta.

PMID- 9605469
TI  - The childhood scars of newborn intensive care.
AB  - Many of the techniques used in newborn intensive care damage the skin and may
      lead to scarring. We have investigated a cohort of consecutive survivors of
      newborn intensive care for the presence of scars. Ninety of the original 100
      children between the ages of 8 and 9 years were examined in detail by a single
      observer--the number, site and severity of the scars were noted and compared with
      the findings when the children were 2 years old. There was an overall reduction
      in the number of scars with time, regardless of gestational age. Scars from
      needlemarks were reduced by 41% and those from intravenous accidents by 70%,
      compared with those seen at 2 years. Scars from chest drains were still visible,
      in two cases requiring corrective surgery. Nine children and their families found
      that the scars caused them embarrassment. The only scars which did not usually
      improve with time and which were often judged to be worse cosmetically were those
      caused by surgery.

PMID- 9605470
TI  - Neonatal neurological examination as a predictor of neuromotor outcome at 4
      months in term low-Apgar-score babies in Zimbabwe.
AB  - The predictive value of the neonatal neurological examination (NNE) adapted from
      Prechtl, was investigated in 139 term Zimbabwean infants born with an Apgar score
      of five or less at 5 min. At 4 months, seven infants had died and 13 were lost to
      follow-up, leaving 119 infants to undergo the Infant Motor Screen (IMS). Eighty
      eight infants were diagnosed as normal, six as suspect and 25 as abnormal at
      screening. The sensitivity, specificity, positive predictive value and negative
      predictive value of the NNE were 94%, 55%, 42% and 96%, respectively. Seventeen
      (14%) infants had developed microcephaly at 4 months and 13 (77%) of them scored
      abnormal on the IMS. Twenty-three of the 48 (48%) infants who had convulsions
      within 48 h of birth, were diagnosed as abnormal (P < 0.0001). The NNE proved to
      be very sensitive in detecting neurodevelopmental abnormalities in the neonatal
      period and the five abnormal syndromes derived from the NNE were able to
      correctly identify 94% of the abnormal infants.

PMID- 9605471
TI  - Heterodimer SRP9/14 is an integral part of the neural BC200 RNP in primate brain.
AB  - BC200 RNA is a brain-specific, small non-messenger RNA with a somatodendritic
      localization in primate neurons and a constituent of a ribonucleoprotein (RNP)
      complex. The primary and secondary structure of the 5' domain of BC200 RNA
      resembles that of the Alu domain of 7SL RNA, which is an integral part of the
      signal recognition particle (SRP). This would predict that similar proteins bind
      to this defined domain of both RNA species in vitro and in vivo. The data
      presented in this paper reveal that a protein that binds BC200 RNA in vivo is
      immunoreactive with antibodies against SRP9. This further supports the notion
      that the 5' domain of the BC200 RNA can fold into structures similar to the SRP
      Alu domain and, as a result, bind identical or similar proteins in vivo. The SRP9
      protein binds only as dimer with SRP14 protein to the Alu domain of 7SL RNA to
      form a subdomain that, in SRP, is functional in translation arrest. Therefore,
      our data also indicate that the neuronal BC200 RNP is a candidate for regulating
      decentralized protein biosynthesis in dendrites, possibly with a mechanism that
      resembles translation arrest of the SRP.

PMID- 9605472
TI  - Neuronal apoptosis in rats is accompanied by rapid impairment of cellular
      respiration and is prevented by scavengers of reactive oxygen species.
AB  - Apoptosis of cerebellar granule cells induced by potassium withdrawal is
      accompanied by a very rapid decrease in both cell and mitochondrial respiration
      supported by glucose and succinate, respectively. The respiratory control ratio,
      which is an index of oxidative phosphorylation and therefore reflects the ability
      of mitochondria to produce ATP, is reduced by 50% within the first 2 h after the
      beginning of apoptosis, insulin-like growth factor I (IGF-I), actinomicin D or
      cycloheximide, previously reported to inhibit apoptosis, fully prevent the
      impairment of cellular respiration while scavengers of reactive oxygen species
      partially inhibit apoptosis and restore cellular respiration.

PMID- 9605473
TI  - Osteogenic protein-1 and related bone morphogenetic proteins regulate dendritic
      growth and the expression of microtubule-associated protein-2 in rat sympathetic
      neurons.
AB  - Osteogenic protein-1 (OP-1) is expressed in the developing nervous system and it
      has been found to induce dendritic growth in sympathetic neurons. To further
      characterize this phenomenon, the effects of OP-1 were compared to those of other
      members of the bone morphogenetic protein (BMP) family of growth factors.
      Recombinant human OP-1, BMP-6, BMP-2 and the Drosophila 60A protein induced
      dendritic growth in rat sympathetic neurons in a concentration-dependent manner
      with EC50-values of 1.8, 1.0, 1.7 and 2.7 ng/ml, respectively. In contrast, BMP-3
      and cartilage-derived morphogenetic protein-2 (CDMP-2) as well as other classes
      of growth factors were inactive at concentrations up to 50 ng/ml. The dendritic
      growth induced by OP-1, BMP-6, BMP-2 and 60A was accompanied by increased
      expression of microtubule-associated protein-2 (MAP2) without changes in the
      expression of the phosphorylated forms of the M and H neurofilament subunits.
      These results suggest that several members of the BMP family have the capacity to
      regulate the morphological development of sympathetic neurons and that they may
      act by induction of specific cytoskeletal proteins.

PMID- 9605474
TI  - In rat hippocampal slices, NMDA receptor-mediated EPSPs are more sensitive to
      hypoxia than AMPA receptor-mediated EPSPs.
AB  - In slices kept at 33 degrees C, N-methyl-D-aspartate (NMDA) receptor- and (+/-)
      alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor-mediated
      field excitatory post-synaptic potentials (EPSPs) were pharmacologically isolated
      in CA1. Both types of EPSPs were reversibly blocked by 3 min of hypoxia (95%
      N2/5% CO2); but NMDA receptor-mediated EPSPs were consistently blocked earlier
      and recovered later than AMPA receptor-mediated EPSPs, recorded in the same
      slice. This difference may be due to inactivation of NMDA receptors by hypoxia
      induced acidity and/or rise in internal [Ca2+].

PMID- 9605475
TI  - Age-related changes in nicotinic acetylcholine receptor subunits alpha4 and beta2
      messenger RNA expression in postmortem human frontal cortex and hippocampus.
AB  - Age-related changes in nicotinic acetylcholine receptor (nAChR) subunit alpha4
      and beta2 messenger RNA (mRNA) expression in the postmortem human frontal cortex
      and hippocampus was investigated using the reverse transcription-polymerase chain
      reaction (RT-PCR). In the frontal cortex, both alpha4 and beta2 subunit mRNA
      expression decreased with age. In the hippocampus, alpha4 subunit mRNA expression
      was unaltered, while beta2 subunit mRNA expression significantly decreased with
      age. These findings suggest that nAChR transcription decreases during aging with
      differing vulnerability between subunits and brain regions, which could in part
      contribute to the reduction in cognitive functions seen in the elderly.

PMID- 9605476
TI  - Effects of ethylene glycol tetraacetic acid, A23187 and calmodulin, calcium
      activated neutral proteinase antagonists on melatonin secretion in perifused
      chick pineal gland.
AB  - We have recently described, using perifused pineal glands, that calcium influx
      participates in the activation of chick pineal gland. This study shows that the
      loss of perifused chick pineal gland activity is a complex process which seems to
      involve the release of calcium from intracellular stores, calmodulin and calcium
      activated neutral protease (CANP). Pineal glands were perifused with Krebs medium
      (controls) or with Krebs medium plus the drugs ethylene glycol tetraacetic acid
      (EGTA; calcium chelator), A23187 (calcium ionophore), EGTA plus A23187 (extra
      intra cellular calcium chelation), trifluoperazine and CGS9343B (calmodulin
      inhibitors), and E-64 (CANP inhibitor) at the time of the natural peak of
      melatonin release. When EGTA or A23187 were added to the perifusion medium, no
      effects were observed. On the other hand, when the calcium chelator EGTA plus
      A23187 (free extra and intracellular calcium levels were dramatically decreased),
      trifluoperazine, CGS 9343B or E-64 were added to the perifusion medium melatonin
      synthesis increased significantly and was sustained for 8 h. We propose a
      prominent role for calcium output from intracellular stores in regulating
      melatonin production primarily by acting on Ca-calmodulin and calcium-activated
      neutral protease.

PMID- 9605477
TI  - Relationship between fluctuations in the cerebral hemoglobin oxygenation state
      and neuronal activity under resting conditions in man.
AB  - Simultaneous measurements by near-infrared spectroscopy and
      electroencephalography were performed during 15-min resting periods in nine
      healthy adult brains. The peak frequencies of the frontal and occipital rhythms
      varied with the time course like the hemoglobin oxygenation state. Changes in the
      amount of oxygenated hemoglobin in the frontal region by more than 50% of the
      maximum resting variation range were accompanied by changes in peak frequency at
      the electrode position between two optodes. The results suggest that spontaneous
      neuronal activity is responsible for fluctuations in the hemoglobin oxygenation
      state in the resting state.

PMID- 9605478
TI  - Sprouting of the serotonergic afferents into striatum after selective lesion of
      the dopaminergic system by MPTP in adult mice.
AB  - Neonatal destruction of the nigrostrial dopaminergic (DA) system with 6
      hydroxydopamine leads to serotonergic (5-HT) hyperinnervation of the striatum.
      However, it is not clear whether this occurs in adult animals. We investigated
      whether serotonergic sprouting occurs in adult mice subjected to bilateral lesion
      of the DA system by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The
      effects of the lesion were evaluated using a new rotarod test and
      immunohistochemistry. One hundred days after the last MPTP lesion, there was a
      clear bilateral serotonergic hyperinnervation throughout the striatum.
      Additionally, those mice showing the highest reductions in striatal tyrosine
      hydroxylase (TH) immunoreactivity and in rotarod performance showed the highest
      density of serotonergic innervation (116% increase). The functional consequences
      of this process in Parkinson's disease and secondary parkinsonism remain to be
      clarified.

PMID- 9605479
TI  - Training improves the adaptation to changing visual conditions in maintaining
      human posture control in a test of sinusoidal oscillation of the support.
AB  - Balance control relies on somesthetic, visual and vestibular afferences, their
      central processing, and adequate motor responses. We studied the consequences on
      postural control of the suppression of visual afferences by eye closure, during a
      dynamic posturographic test in six sportsmen and 14 non-sportsmen. Suppression of
      visual afferences during the test led to a prolongation of the pattern initially
      recorded with eyes open, followed by a transitory adaptive pattern, then a
      typical eyes closed pattern. Repetition of the test showed a progressively longer
      persistence of the eyes open pattern and disappearance of the adaptive one. This
      evolution was significantly faster in sportsmen. This progressively longer
      duration of the eyes open pattern may be explained by the intervention of short
      term memory. Our data further indicate that training improves adaptive posture
      control.

PMID- 9605480
TI  - Alteration of myo-inositol monophosphatase in Alzheimer's disease brains.
AB  - myo-Inositol monophosphatase (E.C.3.1.3.25) catalyzes the hydrolysis of myo
      inositol 1-phosphate in the presence of Mg2+ at a physiologic pH to form free myo
      inositol, maintaining a supply that represents the precursor for inositol
      phospholipid second messenger signaling systems. In the present study the
      activity and protein level of myo-inositol monophosphatase were investigated in
      samples from normal human and Alzheimer's disease (AD) postmortem brains. The
      separation profile on Sephadex G-100 gel filtration chromatography revealed one
      major form of myo-inositol monophosphatase in crude extracts from both normal
      human and AD brains. In AD brains myo-inositol monophosphatase activity and its
      protein level were significantly higher than in control brains. The activity of
      myo-inositol monophosphatase per enzyme molecule was similar in control and AD
      brains. These results suggest that myo-inositol monophosphatase is upregulated in
      AD, probably reflecting compensatory mechanisms concerned with phospholipid
      metabolism.

PMID- 9605481
TI  - Metabolic disturbances in hippocampal slices of fetal guinea pigs during and
      after oxygen-glucose deprivation: is nitric oxide involved?
AB  - The aim of this study was to investigate the role of nitric oxide in metabolic
      disturbances induced in brain tissue of fetal guinea pigs by oxygen-glucose
      deprivation. Experiments were performed on hippocampal slices so as to exclude
      the effects of nitric oxide on the cardiovascular system. Metabolic disturbances
      were assessed by measuring changes in energy metabolism and protein synthesis
      after different periods of oxygen-glucose deprivation (OGD). Ten min after OGD of
      40 min duration, the concentration of cGMP in tissue slices rose from 1.35 +/-
      0.38 to 18.6 +/- 1.04 pmol/mg protein (P < 0.05). This rise was almost completely
      inhibited by the addition of 100 microM N-nitro-L-arginine (NNLA), indicating
      that NO-synthase was strongly activated after OGD in fetal brain tissue. However,
      addition of NNLA improved neither protein synthesis nor energy metabolism
      measured 12 h after OGD. Thus, nitric oxide does not appear to contribute
      directly to processes leading to metabolic disturbances induced by transient
      ischemia in immature brain tissue.

PMID- 9605482
TI  - Binocular behavior of split-brain cats which have previously learned monocularly
      opposite visual discriminations.
AB  - Twelve adult split-brain cats were tested binocularly in visual tasks which had
      been previously learned monocularly in a two-choice paradigm. Eight experimental
      cats learned two opposite tasks with two eyes because contingencies of
      reinforcement changed with the open eye. Four control cats learned the same tasks
      but contingencies of reinforcement did not change with the open eye and therefore
      they learned the same problems with the two eyes. Thereafter, cats were submitted
      binocularly to the same tasks but in a free-choice paradigm. Experimental cats
      showed extinction of the discriminative response in 12 out of 16 binocular
      testings; in four the extinction criterion was not reached. In control cats no
      extinction behavior was observed in seven out of eight testings. It is suggested
      that extinction of the discriminative response in experimental cats could be
      caused by an inhibitory effect build-up because the two hemispheres attempted to
      control binocular behavior in opposite ways. Alternatively, these cats may
      develop a response alternative to discrimination in which one hemisphere takes
      the control of subcortical motor and/or attentional centers. In four testings no
      extinction was recorded for experimental cats and it is likely that control of
      those centers shifted from one hemisphere to the other every few trials.

PMID- 9605483
TI  - Suppression of somatosensory evoked potentials by nitric oxide synthase
      inhibition in rats: methodological differences.
AB  - We have previously shown that topically applied N(G)-nitro-L-arginine (L-NNA), a
      nitric oxide synthase (NOS) inhibitor, suppressed both somatosensory evoked
      potentials (SEPs) and vascular responses during sciatic nerve stimulation in
      rats. Due to the normal tight coupling between cerebral blood flow and neuronal
      activity, we surmise that the vascular response attenuation may be secondary to
      the SEP decrease. However, a recent study, in which SEPs were recorded with a
      'non-contact' electrode placed longitudinally across the cranial window without
      touching the cortex, did not find a SEP decrease following NOS inhibition. In the
      present study, we compared SEPs recorded with 'contact' and 'non-contact'
      electrodes. Regardless of stimulation methods (sciatic nerve or hindpaw), an
      electrode in contact with the pial surface overlying the hindlimb somatosensory
      cortex recorded a steady SEP decline during I-NNA application. In contrast, a
      'non-contact' electrode did not detect a significant SEP change in the presence
      of I-NNA. The present results thus confirm the attenuation of SEPs by NOS
      inhibition.

PMID- 9605484
TI  - Effect of acute, but not chronic ethanol treatment on somatostatin secretion in
      rat hypothalamic neurons.
AB  - To examine the possible involvement of somatostatin in growth hormone
      modifications induced by ethanol, we examined: (1) the effects of chronic ethanol
      exposure of cultured hypothalamic neurons on somatostatin content and mRNA
      levels; (2) the acute effect of ethanol on somatostatin release stimulated by N
      methyl-D-aspartate (NMDA). The results showed that 8 days of ethanol exposure (10
      100 mM) did not decrease somatostatin content or somatostatin mRNA levels.
      Ethanol treatment alone had no significant effect on cell morphology or on
      protein content. In contrast, acute application of ethanol in 8 day-old cultures
      significantly reduced (50 mM) or completely blocked (100 mM) somatostatin release
      elicited by 50 microM NMDA without modifying basal release. We conclude that
      chronic ethanol treatment to concentrations up to 100 mM has no effect on
      somatostatin biosynthesis in fetal rat hypothalamic neurons, while weaker
      concentrations decrease NMDA-induced somatostatin release.

PMID- 9605485
TI  - Melatonin protects nigral dopaminergic neurons from 1-methyl-4-phenylpyridinium
      (MPP+) neurotoxicity in rats.
AB  - In the present study, the in vivo neuroprotective effects of melatonin, as an
      antioxidant, were assessed in Sprague-Dawley rats with a unilateral lesion of
      substantia nigra (SN) caused by a stereotaxic injection of neurotoxin, 1-methyl-4
      phenylpyridinium (MPP+). When expressed as a percentage ratio of lesioned to
      intact side, increased lipid peroxidation product (malondialdehyde, MDA, 117% of
      control) and decreased tyrosine hydroxylase (TH) enzyme activity (60% of control)
      in SN were observed 4 h after MPP+ lesion. In contrast, however, melatonin
      treatment prevented MPP+ neurotoxicity by the almost complete recovery of MDA
      (99% of control) and TH levels (96% of control), indicating the potent
      antioxidative effects of melatonin. In addition, further reduction of TH enzyme
      activity (52% of control) was seen 1 week after MPP+ infusion. Continuous (twice
      a day for 5 days), not acute (4 h) treatment with melatonin produced the partial,
      but not statistically significant, recovery of TH enzyme activity (71% of
      control), when sacrificed 1 week after MPP+ lesion. Taken together, the present
      results support the hypothesis that melatonin may provide the useful therapeutic
      strategies for the treatment of oxidative stress-induced neurodegenerative
      disease such as Parkinson's disease (PD).

PMID- 9605486
TI  - Cell kinetics of surgically induced spinal open neural tube defect in chick
      embryos.
AB  - In an attempt to understand cell kinetics of open neural tube defects (ONTDs) in
      the embryonic stages, chronological changes of cell proliferation and cell death
      patterns in the surgically induced spinal ONTDs of chick embryos were
      investigated using proliferating cell nuclear antigen (PCNA) staining and
      terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP)
      nick end labeling (TUNEL) method. ONTDs were induced at Hamburger and Hamilton
      stages 17-19. Compared with the control group, the surgery group showed a lower
      PCNA labeling index for 5 days after surgery and demonstrated more TUNEL-positive
      cells at 6 h, 3 and 5 days after surgery. Decreased cell proliferation and
      enhanced apoptosis were seen in the ventral as well as in the dorsal spinal cord.
      These results partly explain the functional deficits of ONTDs.

PMID- 9605487
TI  - A live non-neurovirulent herpes simplex virus vector expresses beta-galactosidase
      in the nervous system of the Wistar and Sprague-Dawley strain rat for a prolonged
      period.
AB  - We have constructed a live non-neurovirulent herpes simplex virus vector
      expressing beta-galactosidase under the control of the latency associated
      transcript promoter without inducing inflammation. Pathogenicity of the
      recombinant virus (betaH1) was not observed in the cutaneous, intravenous and
      intracerebral infection in mice. When betaH1 was inoculated at the caudate
      putamen of rats, beta-galactosidase activity was observed in neurons at the
      inoculation site and its projecting frontal cortex. Expression of beta
      galactosidase was observed in the neurons of the innervating dorsal root ganglia
      45 days after inoculation of betaH1 into the hind paws of the rats. Neither
      inflammation nor tissue destruction was observed in both neural tissues in this
      study. Thus this non-neurovirulent recombinant virus is a suitable vector for
      expressing the foreign genes in the nervous system for the prolonged period.

PMID- 9605488
TI  - One-to-one synchronization between the cardiac sympathetic nerve stimuli and
      heart beats in rats.
AB  - One-to-one synchronization of heart rate to the cardiac sympathetic nerve stimuli
      was observed in Sprague-Dawley rats. Propranolol and L-propranolol, but not D
      propranolol, blocked 1:1 synchronization evoked by the nerve stimulation. Thus,
      1:1 synchronization is entirely ascribable to neurally released norepinephrine.
      When a single volley was applied to the cardiac sympathetic nerve, there was a
      significant abbreviation of the respective cardiac cycle at which the stimulus
      fell. The mean latency was 33.1 +/- 2.29 ms (mean +/- SE). The extent of the
      abbreviation of the cardiac cycle was linearly correlated to the interval between
      P wave and a nerve stimulus. These results ensure that the effect of the
      sympathetic nerve stimulation is phase dependent and that the sympathetic nerve
      can entrain the heart beat as well as the parasympathetic nerve can.

PMID- 9605489
TI  - Differences in the effects of zolpidem and diazepam on recurrent inhibition and
      long-term potentiation in rat hippocampal slices.
AB  - We used the CA1 region of rat hippocampal slices to compare the effects of non
      benzodiazepine zolpidem, which binds preferentially to the omega1 sites of gamma
      aminobutyric acid A (GABA(A)) receptors, and of benzodiazepine diazepam, which
      binds equipotently to the omega1 and omega2 sites, on the hippocampal inhibitory
      mechanism and on long-term potentiation (LTP), a possible cellular mechanism for
      memory. First, 1 microM diazepam had an enhancing effect on recurrent inhibition
      by alveus stimulation of orthodromically-induced population spikes, but 1 microM
      zolpidem had no significant effect. Second, 1 microM diazepam blocked LTP
      induction of the population spikes, whereas 1 microM zolpidem had no such effect.
      Only at a higher concentration of 10 microM, zolpidem had a significant effect on
      recurrent inhibition and LTP. These findings suggest that only the omega2 sites
      are mainly involved in modulation of the hippocampal inhibitory mechanism and
      LTP, and that the low affinity of zolpidem for the omega2 sites may account for
      less memory impairment caused by zolpidem than by benzodiazepines.

PMID- 9605490
TI  - Spinocerebellar Purkinje cells and rat forelimb postures: a direction-dependent
      activity.
AB  - On anesthetized adult rats, we examined the possibility that the discharges of
      spinocerebellar Purkinje cells (PCs) are modulated by passive limb positioning.
      The rat forelimb was passively placed in four different sagittal positions while
      the simple spike spontaneous activity of single PCs was recorded; recordings
      started 5 s after the reaching of the posture and the forelimb remained at each
      position for at least 30 s. Although the activity of the PCs did not reflect the
      forelimb position, it showed hysteresis that depended in a cosine fashion on the
      direction of the preceding movement. This implies that the directional
      sensitivity of spinocerebellar PCs is persistent, since the activity levels were
      almost constant throughout the recording time.

PMID- 9605491
TI  - The antiepileptic drug AWD 131-138 stimulates different recombinant isoforms of
      the rat GABA(A) receptor through the benzodiazepine binding site.
AB  - Recombinant gamma-aminobutyric acid A (GABA(A)) receptors of the subunit
      compositions alpha1beta2gamma2, alpha1beta3gamma2, alpha2beta2gamma2,
      alpha3beta2gamma2 and alpha5beta2gamma2 were expressed in Xenopus oocytes in a
      functionally active form. At all subunit combinations, AWD 131-138 dose
      dependently stimulated GABA currents. At 10 microM AWD 131-138, this allosteric
      stimulation amounted in average to about 12-21% of the maximal stimulation
      achieved using diazepam. The threshold of stimulation was about 0.3-1.0 microM.
      One micrometer of the benzodiazepine antagonist flumazenil (Ro 15-1788)
      counteracted the current stimulation by 10 microM AWD 131-138, indicating that
      this drug acts at the binding site for benzodiazepines.

PMID- 9605492
TI  - Sympathectomy does not affect the early ectopic discharge from myelinated fibres
      in ferret inferior alveolar nerve neuromas.
AB  - Ectopic neural activity from damaged axons is thought to contribute to the
      development of sensory disorders following nerve injury. Here we have studied the
      role of sympathetic fibres in the generation or potentiation of this abnormal
      activity by determining the effect of predegenerating these fibres. Twelve adult
      ferrets were used in the study and six of them underwent sympathectomy by removal
      of the left superior cervical ganglion. Electrophysiological recordings were made
      from myelinated axons in fine filaments dissected from the inferior alveolar
      nerve, 3 days after it had been ligated further distally, and the level of
      spontaneous activity and mechanical sensitivity was determined. There was no
      significant difference between the level or characteristics of spontaneous
      activity, or the level of mechanical sensitivity, in the two groups of animals.
      We conclude that, in this animal model, the absence of sympathetic nerve fibres
      does not affect the development or characteristics of ectopic neural activity in
      the early period following nerve injury.

PMID- 9605493
TI  - The phosphorylated isoform of microtubule associated protein 1B (MAP1B) is
      expressed in the visual system of the tench (Tinca tinca, L) during optic nerve
      regeneration.
AB  - By using Western blot analysis and immunohistochemistry we have demonstrated that
      microtubule associated protein 1B (MAP1B)-phos is present in growing and
      regenerating axons of retinal ganglion cells of fish (Tinca tinca, L). We have
      found that the levels of MAP1B-phos substantially increase in regenerating optic
      nerves. Our observations suggest that MAP1 B-phos plays an important role in
      regeneration processes in the central nervous system (CNS) of the fish. These
      results are compared in the present paper with that found in the regenerating
      peripheral nervous system (PNS) of mammals.

PMID- 9605494
TI  - Light of domestic intensity produces phase shifts of the circadian oscillator in
      humans.
AB  - Twelve subjects have been studied in a chamber that isolated them from external
      noise and lighting. After several control days, one group (n = 6) was subjected
      to 18 x 27-h 'days' and the other to 11 x 30-h 'days'. Sleep was in the dark, and
      awake times were spent in normal domestic lighting (150-500 lux). Rectal
      temperature and wrist actimetry were measured throughout, and the phase of the
      circadian oscillator was inferred from that of the temperature data, purified to
      remove direct effects of activity. During the experimental 'days' the rhythms
      showed a mean period of 24.4 h. A detailed examination of the phase shifts from
      one day to the next showed that small advances and delays were superimposed upon
      this drift. Moreover, the mean size and direction of these shifts depended upon
      the time of exposure to lighting relative to the temperature minimum, as would be
      predicted from a phase-response curve.

PMID- 9605495
TI  - Modulation of cell responses to horizontal disparities by ocular vergence in the
      visual cortex of the awake Macaca mulatta monkey.
AB  - Horizontal retinal disparity is the most important cue for stereopsis. However,
      accurate stereoscopic perception requires additional information on fixation
      distance. The ocular vergence angle may provide information on fixation distance
      and therefore may be used to calibrate horizontal disparities. We studied the
      responses of cells from cortical visual area V1 of one macaca mulatta monkey to
      dynamic random dot stereograms at different ocular vergence angles. We observed
      that in about half of cells sensitive to horizontal disparity the vergence angle
      modifies the cell responses to horizontal disparities. These results suggest that
      vergence angle may be used to calibrate horizontal disparities for fixation
      distance.

PMID- 9605497
TI  - Central administration of a nitric oxide synthase inhibitor causes pressor
      responses via the sympathetic nervous system and the renin-angiotensin system in
      Wistar rats.
AB  - The central roles of nitric oxide (NO) in regulations of the blood pressure and
      heart rate were examined in anesthetized rats. Intracerebroventricular (i.c.v.)
      injection of Nomega-nitro-L-arginine methyl ester (L-NAME) caused dose-dependent
      increase in the blood pressure and heart rate. The pressor response of the blood
      pressure to L-NAME (2 micromol, i.c.v.) was reduced by L-arginine (5 micromol,
      i.c.v). Pretreatment with a ganglionic blocker, pentolinium (10 mg/kg, i.v.),
      significantly inhibited both pressor responses induced by L-NAME (2 micromol,
      i.c.v). The later pressor response of the blood pressure to L-NAME was also
      inhibited by the angiotensin II AT-1 blocker losartan (10 mg/kg, i.v). These
      results suggest that the response of the blood pressure to L-NAME is mediated by
      both the sympathetic nervous system and the renin-angiotensin system.

PMID- 9605496
TI  - Human apolipoprotein E accelerates microtubule polymerization in vitro.
AB  - Apolipoprotein E (apoE) is a 34-kDa protein implicated in Alzheimer's disease
      (AD) that has recently been identified in neuronal cytoplasm. In cultured
      neurons, the two major isoforms of apoE (E3 and E4) differentially affect neurite
      extension, microtubule formation, and the ratio of polymerized to depolymerized
      tubulin. We therefore examined the effects of apoE3 and apoE4 on microtubule
      assembly in vitro. ApoE3 and apoE4 equally accelerated microtubule polymerization
      under conditions of slow microtubule assembly. Controls comprising apolipoprotein
      A1, bovine serum albumin, trypsin inhibitor, and boiled apoE had no effect,
      demonstrating specificity of the apoE effect. The ability of both apoE isoforms
      to accelerate microtubule assembly in vitro suggests that isoform-specific
      differences in neurite extension may result from differences in the uptake,
      intracytoplasmic transport, or metabolism of these isoforms.

PMID- 9605498
TI  - Circadian expression of serotonin N-acetyltransferase mRNA in the rat retina.
AB  - To investigate the molecular mechanism of the melatonin rhythm in the mammalian
      retina, we examined the temporal mRNA expression pattern of serotonin N
      acetyltransferase (arylalkylamine N-acetyltransferase, AA-NAT; the rate-limiting
      enzyme in melatonin synthesis) in the rat retina. Northern blot analysis showed
      that in a daily light-dark cycle retinal AA-NAT mRNA was low during the day and
      increased more than threefold at night, and this daily rhythm persisted even in
      constant darkness. These findings suggest that AA-NAT mRNA expression in the rat
      retina is regulated by an endogenous circadian clock.

PMID- 9605499
TI  - Age-related decline of F3/contactin in rat hippocampus.
AB  - F3/Contactin (F3), a neural adhesion molecule, is known to be involved in
      developmental and regenerative processes in the brain. We have investigated age
      related change in the expression of F3 mRNA and protein in the Wistar rat brain
      using immunohistochemistry and in situ hybridization. From 3 months to 24 months,
      no obvious change in the amount of F3 protein was observed in cerebral cortex,
      hippocampus and cerebellum. However, in 30-month-old rats a significant decrease
      in F3 protein was found in the hippocampus. A specific decrease of density of F3
      immunostaining and F3 mRNA expression was observed in the pyramidal neurons of
      CA1 and the granule cells in dentate gyrus. The specific decrease of F3 in the
      hippocampus at late stage of aging may be related to memory deficient in old age.

PMID- 9605500
TI  - Cerebrospinal fluid homovanillic acid levels are not reduced in early
      corticobasal degeneration.
AB  - To investigate the contribution of nigral degeneration to the development of
      parkinsonism in the early stages of corticobasal degeneration (CBD), we measured
      the cerebrospinal fluid (CSF) levels of homovanillic acid (HVA) in patients with
      early CBD (n = 5), and compared the levels with those in patients with early
      Parkinson's disease (n = 11) and in normal subjects (n = 13). The mean CSF HVA
      level in the early CBD group (33.1 +/- 6.0 ng/ml) did not differ significantly
      from that in the control group (37.1 +/- 12.7 ng/ml), whereas that in the early
      Parkinson's disease group (19.0 +/- 7.6 ng/ml) was reduced significantly (P <
      0.001). This result suggests that neuronal cell loss in the substantia nigra and
      presynaptic nigrostriatal dopaminergic neuron dysfunction are mild in the early
      stages of CBD.

PMID- 9605501
TI  - Influence of monovalent cations on yeast cytoplasmic and vacuolar pH.
AB  - The effects of monovalent cations on the internal pH of yeast were studied. Our
      former procedure was modified, inducing maximal alkalinization of the cells with
      100 mM-NH4OH instead of Tris base. The pH values were lower than reported before
      (Pena et al., J. Baceteriol. 1995 177, 1017-1022). With glucose as substrate, the
      internal cytoplasmic pH reached higher values when incubating at an external pH
      of 6.0, as compared to pH 4.0. Monovalent cations added approximately 5 min after
      glucose produced a further increase in the internal pH, which was higher at a
      previous incubation pH of 4.0 than that observed at pH 6.0. The selectivity of
      the changes followed a similar order to that of the transport system for
      monovalent cations. When incubating cells with glucose for more than 30 min, the
      initial changes of the internal pH appeared to be regulated by the cell. However,
      under the fluorescence microscope, it was observed that pyranine, which was
      confined to the cytoplasm during the first 15 min, was progressively concentrated
      in the vacuole. By studying the fluorescence changes of cells electroporated and
      then incubated with glucose or glucose plus potassium, we could follow the
      internal pH of this organelle, obtaining values within the range reported by
      other authors. Also, in cells preincubated with glucose for 60 min, and
      electroporated afterwards, the fluorescence of pyranine, which only entered the
      cytoplasm, allowed us to measure the pH of this compartment, showing that it was
      more alkaline than the vacuole. Moreover, the cytoplasmic pH increased upon
      addition of glucose or potassium. The vacuolar pH, on the other hand, increased
      upon addition of potassium after glucose, but decreased upon addition of glucose.
      In addition, incubation of the cells with glucose with or without pyranine
      produced vesiculation of the vacuole.

PMID- 9605502
TI  - Induced expression of the Candida albicans multidrug resistance gene CDR1 in
      response to fluconazole and other antifungals.
AB  - The Candida albicans CDR1 gene encodes a member of the ABC-type family of
      multidrug transporters which has been shown to be involved in azole resistance.
      Using an in-frame gene fusion between the CDR1 open reading frame and the green
      fluorescent protein allele yEGFP3, an optimized derivative for its use in C.
      albicans, we show here how the CDR1-yEGFP3 gene expression is induced in response
      to azoles as well as to other structurally unrelated drugs like cycloheximide.
      Moderate increases were observed for calcofluor, canavanine, 5'-fluorcytosine,
      cilofungin and caffeine, while no induction was found for the antifungals benomyl
      and amphotericin B or hydrogen peroxide at subinhibitory concentrations. The use
      of confocal microscopy enabled us to localize the Cdr1p fusion protein at the
      cell periphery, thus suggesting a cytoplasmic membrane localization. These
      results suggest deregulation of CDR1 gene as a putative mechanism for the
      generation of azole resistance in this clinically important pathogenic fungus.

PMID- 9605503
TI  - Identification of YHR019 in Saccharomyces cerevisiae chromosome VIII as the gene
      for the cytosolic asparaginyl-tRNA synthetase.
AB  - Exploiting the asparagine auxotrophy of the Saccharomyces cerevisiae mutant
      strain 8556a, we have isolated the gene for the cytosolic asparaginyl-tRNA
      synthetase (AsnRS) of S. cerevisiae, by functional complementation of the
      mutation affecting this strain. The isolated gene could be identified to the open
      reading frame YHR019, called DED81, located on chromosome VIII. The mutant gene
      from the 8556a strain, asnrs-1, was amplified from genomic DNA by PCR. This gene
      contains a point mutation, leading to the replacement of a glycine residue by a
      serine in a region of the protein probably important for the asparaginyl
      adenylate recognition. The protein encoded by YHR019 is very similar to cytosolic
      AsnRS from other eukaryotic sources. In a phylogenetic analysis based on AsnRS
      sequences from various organisms, the eukaryotic sequences were clustered.
      Expression of YHR019 in Escherichia coli demonstrated that a yeast AsnRS activity
      was produced. The recombinant enzyme was purified to homogeneity in three
      chromatography steps. We showed that the recombinant S. cerevisiae AsnRS was able
      to charge unfractionated yeast tRNA, but not E. coli tRNA, with asparagine.

PMID- 9605504
TI  - Deletion of transmembrane domain 12 of CDR1, a multidrug transporter from Candida
      albicans, leads to altered drug specificity: expression of a yeast multidrug
      transporter in baculovirus expression system.
AB  - Cdr1p, an ATP-binding cassette transporter from the pathogenic yeast Candida
      albicans, confers resistance to several unrelated drugs including anti-Candida
      drugs (Prasad et al., 1995b). We demonstrate that the deletion of 237 bp (79 aa)
      from the 3' end of CDR1 (which encompasses the transmembrane domain (TM) 12 of
      the putative transporter) did not result in the total loss of its ability to
      efflux cytotoxic agents. While the expression of deltaCDR1 in yeast resulted in
      impaired sensitivity to drugs like cycloheximide, anisomycin, sulfomethuron
      methyl and antifungal nystatin, its ability to confer resistance remained
      unaltered to drugs such as o-phenanthroline, 4-nitroquinoline-N-oxide, cerulenin,
      azoles, oligomycin, erythromycin, and benomyl. Similar to human MDR1p. Cdr1p
      might also have localized drug binding sites in TM 12, but that might not be the
      case for all the drugs. The TM 12 deletion also did not lead to any significant
      impairment in NTPase activities. Both ATPase and UTPase activities of complete
      Cdr1p and deltaCdr1p were not significantly altered, as was the case with respect
      to their ability to efflux Rh123 and steroid hormone like [3H]-beta-estradiol. To
      further dissect the functionality of Cdr1p, its truncated version was
      overexpressed in a baculovirus-insect cell expression system. The synthesis of
      deltaCdr1p in Sf9 cells was temporally regulated as a function of the baculovirus
      polyhedrin gene promoter. The Sf9 derived deltaCdr1p was approximately 130 kDa,
      which was lower than the expected size, probably due to the differences in
      glycosylation. This, however, did not affect the functionality of deltaCdr1p. The
      deletion of TM 12 did not affect the targeting of the protein and deltaCdr1p was
      exclusively localized in plasma membrane of Sf9 cells as detected by
      immunofluorescence. The expression of deltaCdr1p in the baculovirus-insect
      expression system generated a high drug-stimulated plasma membrane-bound ATPase
      activity which was not demonstrable when deltaCdr1p was expressed in yeast.

PMID- 9605506
TI  - An improved protocol for the preparation of yeast cells for transformation by
      electroporation.
AB  - Pretreatment of yeast cells with lithium acetate (LiAc) and dithiothreitol (DTT)
      enhances the frequency of transformation by electroporation. The method shows
      improvements of 6-67-fold in wild-type strains derived from commonly used
      Saccharomyces cerevisiae genetic backgrounds. In addition, 15-300-fold
      improvement in transformation frequency was achieved with several mutant strains
      of S. cerevisiae that transformed poorly by conventional procedures. Both DTT and
      lithium acetate were necessary for maximal transformation frequencies.
      Pretreatment with lithium and DTT also resulted in an approximately 3-5-fold
      increase in the electroporation transformation frequency of the pathogenic fungus
      Candida albicans.

PMID- 9605505
TI  - A family of laboratory strains of Saccharomyces cerevisiae carry rearrangements
      involving chromosomes I and III.
AB  - In order to study meiotic segregation of chromosome length polymorphism in yeast,
      we analysed the progeny of a cross involving two laboratory strains FL100trp and
      YNN295. Analysis of the parental strains led us to detect an important length
      polymorphism of chromosomes I and III in FL100trp. A reciprocal translocation
      involving 80 kb of the left arm of chromosome III and 45 kb of the right arm of
      chromosome I was shown to be the cause for the observed polymorphism in this
      strain. The characterization of the translocation breakpoints revealed the
      existence of a transposition hot-spot on chromosome I: the sequence of the
      translocation joints on chromosomes I and III suggests that the mechanism very
      likely involved homologous recombination between Ty2 transposable elements on
      each chromosome. Analysis of FL100, FL200 and FL100trp ura, which are related to
      FL100trp, shows that this reciprocal translocation is present in some of the
      strains of the FL series, whereas the parental strain FL100 does not carry the
      same rearrangement. We evidenced instead the duplication of 80 kb of chromosome
      III on chromosome I and a deletion of 45 kb of the right arm of chromosome I in
      this strain, indicating that secondary events might have taken place and that the
      strain currently named FL100 is not the common ancestor of the FL series.

PMID- 9605507
TI  - Cloning and sequencing of a cDNA encoding a copper-zinc superoxide dismutase
      enzyme from the marine yeast Debaryomyces hansenii.
AB  - Cu-Zn superoxide dismutase (SOD-1) is a ubiquitously occurring eukaryotic enzyme
      with a variety of important effects on respiring organisms. A gene (dhsod-1)
      encoding a Cu-Zn superoxide dismutase of the marine yeast Debaryomyces hansenii
      was cloned using mRNA by the RT-PCR technique. The deduced amino-acid sequence
      shows approximately 70% homology with that of cytosolic superoxide dismutase from
      Saccharomyces cerevisiae and Neurospora crassa, as well as lower homologies
      (between 55 and 65%) with the corresponding enzyme of other eukaryotic organisms,
      including human. The gene sequence encodes a protein of 153 amino acids with a
      calculated molecular mass of 15-92 kDa, in agreement with the observed
      characteristics of the purified protein from D. hansenii.

PMID- 9605508
TI  - Homolog of a-factor receptor gene in Saccharomyces exiguus.
AB  - Homologs of Saccharomyces cerevisiae STE3, a-factor receptor gene were detected
      from S. exiguus NFRI 3539 by low stringency Southern hybridization. This strain
      might have at least two types of homolog. One of these homologs, designated as e
      STE3 was cloned. Its nucleotide sequence revealed 60% identity to STE3. The
      putative protein coding region consisted of 453 amino acid residues. The amino
      acid sequence identity between STE3 and e-STE3 was 62% and that of the N-terminal
      303 amino acid residues considered to be the pheromone binding domain was 79%.

PMID- 9605509
TI  - A 9359 bp fragment from the right arm of Saccharomyces cerevisiae chromosome VII
      includes the FOL2 and YTA7 genes and three unknown open reading frames.
AB  - In the framework of the EU programme for systematic sequencing of the
      Saccharomyces cervisiae genome we determined the sequence of a 9359 bp fragment
      of the right arm of chromosome VII. Five open reading frames (ORFs) of at least
      300 nucleotides were found in this region. YGR267c encodes a protein with
      significant similarity to the enzyme GTP-cyclohydrolase I, that controls the
      first step in the biosynthetic pathway leading to various pterins and shows a
      high degree of sequence conservation from bacteria to mammals. We have recently
      demonstrated (Nardese et al., 1996) that YGR267c corresponds to the FOL2 gene,
      previously localized in the same chromosomal region by genetic mapping. The
      protein deduced from YGR270w belongs to the superfamily of putative ATPases
      associated with diverse cellular activities. It corresponds to the YTA7 gene, a
      member of a set of yeast genes coding for putative ATPases with high similarity
      to constituents of the 26S protease. The three ORFs YGR266w, YGR268c and YGR269w
      encode putative products of unknown function, with neither significant similarity
      to proteins in databases nor recognizable domains. YGR268c and YGR269w are
      partially overlapping ORFs: YGR268c seems to correspond to a real gene. whereas
      YGR269w is probably a fortuitous ORF.

PMID- 9605510
TI  - Current awareness on yeast.

PMID- 9605511
TI  - Transcriptional regulation of the glycoprotein hormone alpha-subunit gene by
      pituitary adenylate cyclase-activating polypeptide (PACAP) in alphaT3-1 cells.
AB  - We showed previously that pituitary adenylate cyclase-activating polypeptide
      (PACAP) increases glycoprotein hormone alpha-subunit gene expression and
      secretion in alphaT3-1 cells. We have now used 5'-flanking deletion and clustered
      point mutations of the mouse alpha-subunit promoter fused to the luciferase (LUC)
      reporter gene in transient transfection assays to further characterize the cell
      signaling pathways and sequences involved in responsiveness to PACAP. PACAP
      stimulated LUC activity at a lower concentration than VIP, supporting the notion
      that PACAP acts through type 1 receptors. The effect of PACAP on LUC activity was
      observed by 2 h, peaked at 4-12 h, and persisted until at least 20 h. alphaT3-1
      cells were transfected with mouse alpha-LUC constructs truncated at -507, -424, 
      288, -205, -146, and -133, and treated with PACAP, a cell-permeable cAMP analog
      (8Br-cAMP), phorbol myristate acetate (PMA), or control medium. Transcriptional
      activation by PACAP was highest with the -288 and -205 mouse alpha-LUC vectors (7
      8-fold stimulation) and decreased significantly with truncation of the 5'
      flanking region to -146 or -133. The pattern of alpha-subunit stimulation by cAMP
      closely paralleled that of PACAP. With PMA, stepwise decrements in LUC activity
      were observed between -507 and -424 and, especially, -424 and -288, and there was
      no further loss of activity with deletion to -205, -146, or -133. Clustered point
      mutations in the pituitary glycoprotein hormone basal element (-337 to -330) or
      the gonadotropin-releasing hormone response element (GnRH-RE)(-406 to -399) of
      the -507 to +46 mouse alpha-promoter significantly (P < 0.05) increased and
      decreased, respectively, PACAP's effect on transcriptional activity. These
      results indicate that there are several regions of the mouse alpha-subunit
      promoter that mediate responsiveness to PACAP. The co-localization of PACAP and
      cAMP responsiveness as well as the results of studies involving specific
      inhibitors of protein kinase A (H-89) or protein kinase C (PKC)
      (bisindolylmaleimide) suggests that the action of PACAP on alpha-subunit
      transcription is mediated primarily by the protein kinase A (PKA) pathway.

PMID- 9605512
TI  - Beta receptor isoforms are not essential for thyroid hormone-dependent
      acceleration of PCP-2 and myelin basic protein gene expression in the developing
      brains of neonatal mice.
AB  - In rat pups, thyroid hormone dependent brain development coincides with the
      appearance of the thyroid hormone receptor (TR)beta1 isoform. This finding led to
      the suggestion that TRbeta1 plays an essential role in brain development. The
      recent availability of a mouse TRbeta knockout strain allowed us to test this
      possibility by determining whether TRbeta is essential for the normal
      developmental pattern of expression of two thyroid hormone regulated brain genes,
      myelin basic protein (MBP), and Purkinje cell protein 2 (Pcp-2). Northern
      analysis of total mRNA from the brains of wild-type mice established that, as in
      the rat pup, the initial rate of rise of the MBP and Pcp-2 mRNA is slowed in the
      hypothyroid state. Supporting the effectiveness of TRbeta gene deletion was the
      finding that the thiiodothyronine (T3) nuclear binding capacity in the livers and
      brains of knockout animals was consistent with the fractional contribution of
      TRbeta1 to total binding capacity in the wild-type tissues. Further, no TRbeta1
      could be detected by isoform-specific immunoprecipitation of nuclear receptor
      extracts. However, deletion of the functional TRbeta in the TRbeta knockout mice
      did not affect the normal ontogeny of expression of the Pcp-2 and MBP genes in
      the postnatal pup. We conclude that TRbeta is not essential for the normal
      developmental expression of these T3 dependent brain genes.

PMID- 9605513
TI  - Glucocorticoids suppress basal (but not interleukin-1-supported) ovarian
      phospholipase A2 activity: evidence for glucocorticoid receptor-mediated
      regulation.
AB  - Ovulation may constitute a cyclic, inflammatory-like process, wherein the
      increased expression of interleukin (IL)-1 and the biosynthesis of prostaglandins
      may be established corollaries. In this communication we hypothesize that
      glucocorticoids, potent anti-inflammatory principles, may exert an antiovulatory
      effect by interfering with ovarian IL-1-driven prostaglandin biosynthesis. To
      test this hypothesis, we examined the effect of treatment with dexamethasone on
      the activity of ovarian phospholipase A2 (PLA2), the event-limiting enzyme in
      prostaglandin biosynthesis, and on the gene expression pattern of secretory and
      cytosolic PLA2 (sPLA2 and cPLA2, respectively). Whole ovarian dispersates from
      immature rats were cultured under serum-free conditions for 48 h in the absence
      or presence of dexamethasone. At the conclusion of this culture period, PLA2
      activity was determined in cell sonicates and conditioned media. Parallel probing
      for sPLA2 and cPLA2 transcripts was also undertaken using a solution
      hybridization/RNAse protection assay. Treatment of whole ovarian dispersates with
      dexamethasone produced a significant (P < 0.005) decrease in basal cellular and
      extracellular PLA2 activity to 27 and 40% of controls, respectively. A 5-fold
      decrease in the basal steady state levels of sPLA2 (but not cPLA2) transcripts
      was also noted. Co-treatment with dexamethasone produced complete inhibition of
      IL-1-stimulated cPLA2 transcripts but not of IL-1-supported cellular and
      extracellular PLA2 activity or sPLA2 transcripts. A glucocorticoid receptor
      antagonist (RU486), blocked the ability of dexamethasone to inhibit basal sPLA2
      transcripts and extracellular PLA2 activity. The inhibitory effect of
      dexamethasone proved glucocorticoid-specific in that aldosterone and 17beta
      estradiol were without effect. Taken together, these observations suggest that
      dexamethasone is capable of inhibiting basal (but not IL-1-supported) ovarian
      PLA2 activity, a glucocorticoid receptor-mediated effect due, in part, to a
      decrease in sPLA2 gene expression. Our findings further suggest that sPLA2 and
      cPLA2 are differentially regulated and that they may well differ in their
      relative contribution to ovarian prostaglandin biosynthesis in general and to
      PLA2 activity in particular. To the extent that IL-1 plays a central role in the
      ovulatory process, these findings argue against the view that the chronic
      anovulatory state induced by glucocorticoid excess is due, if only in part, to
      suppression of ovarian IL-1-dependent PLA2 activity.

PMID- 9605514
TI  - Progesterone can participate in down-regulation of the luteinizing hormone
      receptor gene expression and function in cultured murine Leydig cells.
AB  - The intratesticular concentration of progesterone (P) rises up to the micromolar
      range during high-dose luteinizing hormone (LH)/hCG stimulation. The aim of this
      study was to examine whether P is involved in the concomitant down-regulation of
      the LH receptor (R) function. The effects were tested in a mouse Leydig tumor
      cell line (mLTC-1) and in Percoll-purified adult mouse Leydig cells. Pre
      incubation of the mLTC-1 cells for 48 h with P (1-10 micromol/l) decreased in
      dose-dependent fashion their specific binding of [125I]iodo-hCG as well as the
      hCG-induced cAMP production (down to 65 and 40% respectively, of controls, P <
      0.01). Similar effect of P on hCG-induced cAMP production was observed in adult
      mouse Leydig cells following a 24 h incubation in the presence of P (0.3-10
      micromol/l). In addition, P treatment significantly inhibited the expression of a
      transiently transfected murine LHR promoter (715 or 950 bp of the 5' untranslated
      region)-luciferase fusion constructs in mLTC-1 cells (down to 50% of control, P <
      0.01). In accordance, a 6-12 h culture in the presence of 5-10 micromol/l of P
      showed significant down-regulatory effects on the steady state levels of LHR-mRNA
      in mLTC-1 cells. These inhibitory effects of P on the LHR expression and function
      were mimicked by similar concentrations of cortisol, but not by testosterone or
      estradiol. Blocking the steroid synthesis of mLTC-1 cells with 86 micromol/l of
      aminoglutethimide (AMG) partially reversed the down-regulating effect of hCG on
      the LHR-mRNA. Moreover, a 24 h culture in the presence of AMG showed an up
      regulating effect on expression of the LHR promoter-luciferase constructs, and
      including hCG (50 microg/l) in the culture medium enhanced this effect. Hence, in
      the absence of steroidogenesis, hCG up-regulates the LHR promoter expression. In
      conclusion, we present here a novel short-loop regulatory mechanism in murine
      Leydig cells where P exerts a negative effect on LHR expression and function.
      Since Leydig cell P production is dramatically increased during high-dose
      stimulation with LH/hCG, due to blockade of C21 steroid side chain cleavage, the
      present findings offer a function for this steroid in the LHR down-regulation.

PMID- 9605515
TI  - Residual bodies and IL-1alpha stimulate expression of mRNA for IL-1alpha and IL-1
      receptor type I in cultured rat Sertoli cells.
AB  - The cytokine interleukin (IL)-1alpha may be produced both by Sertoli cells and
      immature male germ cells from rat and is thought to play a role in autocrine
      and/or paracrine regulation of the spermatogenesis. The localization of IL-1
      receptors in seminiferous tubules is unknown. In this study we found a
      constitutive expression of IL-1 receptor type I (IL-I RI) mRNA in cultured
      Sertoli cells and peritubular cells from rat, whereas no such transcripts were
      observed in immature germ cells (pachytene spermatocytes and round spermatids).
      An autostimulation of IL-1alpha mRNA synthesis has previously been described in
      other cell types. Stimulation of Sertoli cells with recombinant IL-1alpha for 0-7
      h resulted in a rapid increase in both IL-1alpha and IL-1 RI mRNA. When Sertoli
      cells were cultured with residual bodies for 0-48 h, mRNA levels for both IL
      1alpha and IL-1 RI were increased in a biphasic manner. We suggest that
      phagocytosis of residual bodies triggers an autocrine IL-1alpha loop in Sertoli
      cells where both IL-1alpha and one of its receptors are stimulated.

PMID- 9605516
TI  - Nuclear orphan receptors COUP-TFII and Ear-2: presence in oxytocin-producing
      uterine cells and functional interaction with the oxytocin gene promoter.
AB  - We have previously demonstrated that the oxytocin (OT) gene is expressed in the
      rat uterine epithelium and that its expression is upregulated in vivo and in
      vitro by estrogen. This hormonal regulation is mediated by a hormone response
      element (HRE) located in the OT gene promoter. Here we show that the same OT-HRE
      is also capable of interacting with two novel members of the orphan nuclear
      receptor family, rat COUP-TFII and Ear-2, and that this interaction antagonizes
      the estrogenic induction of the OT promoter. By Northern blot analysis and
      immunocytochemistry, using specific cDNA probes and antibodies, respectively, we
      demonstrate furthermore that both orphan receptors are expressed in uterine
      epithelial cells. Therefore, the present findings indicate that uterine OT gene
      expression is under stimulatory as well as inhibitory influences which are both
      mediated by the same HRE. More detailed analysis of the sequences necessary for
      estrogen receptor action and for orphan receptor action, using site-directed
      mutagenesis, revealed that the specific recognition sequences are overlapping but
      distinct: whereas the (imperfect) palindromic structure of the HRE constitutes
      the estrogen response element (ERE), orphan receptor action relies on an
      underlying direct TGACC repeat which forms part of the OT-HRE structure and
      overlaps with the estrogen response element.

PMID- 9605517
TI  - Immunolocalization of stanniocalcin in human kidney.
AB  - Stanniocalcin (STC) is a mammalian polypeptide hormone that appears to play a
      role in mineral metabolism through its regulatory effects on renal phosphate
      transport. In this report we have characterized tissue-derived STC in humans and
      found it to be a glycosylated, disulfide-linked dimer, with similar physical and
      chemical properties to baculovirus-expressed hormone. The hormone was localized
      to principal and alpha-intercalated cells in the distal half of the nephron. This
      is the first homologous demonstration of STC proteins and cells in human tissue.

PMID- 9605518
TI  - Expression of a fusion gene consisting of the mouse growth hormone-releasing
      hormone gene promoter linked to the SV40 T-antigen gene in transgenic mice.
AB  - Limited information is available concerning the regulation of growth hormone
      releasing hormone (GHRH) gene expression in the hypothalamus, largely because of
      the lack of a suitable cellular model. In an attempt to immortalize hypothalamic
      GHRH-producing neurons, we have generated a transgenic mouse model which
      expresses the simian virus 40 (SV40) T-antigen gene (Tag) under the control of
      the GHRH gene promoter. The transgene contains approximately 5 kb of mouse GHRH
      gene sequences, including 3.5 kb of the 5'-flanking region, the entire
      hypothalamic exon 1 and 1.5 kb of intron 1, fused to the SV40 Tag gene. This
      construct was microinjected into fertilized oocytes. Fourteen of 96 mice born had
      integrated the transgene. These mice were fertile and showed no signs of central
      or peripheral tumors. The pattern of expression of the SV40 Tag gene was analyzed
      in four different transgenic lines by RT-PCR. The tissues tested include:
      hypothalamus, pituitary, cortex, cerebellum, spinal cord, adrenal, testis, spleen
      and lung. Transgene expression was consistently detected in the hypothalamus of
      all lines. In addition, SV40 Tag expression was also detected in the hypothalamus
      by Northern blot analysis in two of the transgenic lines. SV40 Tag expression was
      also detected in the testis of all transgenic lines by RT-PCR. This result was
      not expected since the GHRH gene sequences present in the transgene do not
      include the testis-specific transcription initiation site previously described.
      This suggests that GHRH gene expression in the mouse testis can be directed by
      regulatory sequences located downstream of the testis specific transcription
      start site. We conclude that the promoter region of the GHRH gene included in
      this construct contains the regulatory elements necessary to drive hypothalamic
      and testis expression in vivo. In addition, all mice from one of the transgenic
      lines developed cataracts in both eyes. SV40 Tag expression was detected not only
      in eyes with cataracts, but also, to a lesser extent, in eyes from other
      transgenic lines. Furthermore, the endogenous GHRH gene was found to be expressed
      in the eyes of normal mice.

PMID- 9605519
TI  - Comparison of the functional properties of three different truncated thyroid
      hormone receptors identified in subjects with resistance to thyroid hormone.
AB  - The tau4 domain in the extreme carboxyl (C) terminal region of thyroid hormone
      receptor (TR) is important to transactivation. We identified three truncated
      TRbeta1s with 11 (F451X), 13 (E449X) and 16 (C446X) amino acid deletions within
      this domain in subjects with resistance to thyroid hormone (RTH). F451X and C446X
      were found in a 6-year-old Japanese girl and a 31-year-old American male,
      respectively, who had both severe mental retardation. E449X was identified in a
      16-year-old Japanese boy with no remarkable clinical symptoms except for goiter.
      Transient expression study revealed that all three mutants had negligible T3
      binding and transcriptional activities. Each mutant TRbeta1 exhibited not only
      very strong dominant negative activity against wild TRbeta1, but also marked
      silencing activity. Interestingly, the dominant negative activity and silencing
      activity were significantly stronger in F451X than in E449X and C446X (P < 0.05).
      Gel-shift experiments revealed no apparent differences in homodimer formations of
      wild-type or mutant TRbeta1 proteins and in heterodimer formations with retinoid
      X receptor (RXR). These observations indicate that the tau4 domain affects
      diverse TR functions, and that the region between 11 and 13 C-terminal amino
      acids influences ligand-independent TR functions, including dominant negative and
      silencing activities. The central nervous system involvement is not necessarily
      determined by the dominant negative potency of the mutant TRbeta1 and other
      environmental or genetic factors may influence the RTH manifestations.

PMID- 9605520
TI  - Insulin receptor substrate 1 antisense expression in an hepatoma cell line
      reduces cell proliferation and induces overexpression of the Src homology 2
      domain and collagen protein (SHC).
AB  - In mammalian cells, the insulin receptor substrate 1 protein (IRS-1) is a
      specific substrate for insulin and IGF-1 receptor tyrosine kinases which is
      involved in mediating metabolic and mitogenic actions of insulin and IGFs. In
      order to determine if IRS-1 is also essential in a chicken derived hepatoma cell
      line (LMH cells), IRS-1 gene has been invalidated in these cells. For this, we
      subcloned chicken IRS-1 gene in an antisense orientation into a mammalian
      expression vector driven by the cytomegalovirus early promoter. LMH cells were
      stably transfected with this construct or with the empty vector carrying only the
      neomycin resistance gene and selected for cIRS-1 expression. One subclone, C2,
      showed a complete repression of cIRS-1 expression at both protein and mRNA
      levels. Proliferation of C2 cells was dramatically reduced (54%) compared with
      Neo(r) cells. Furthermore this reduction was accompanied by a decrease in insulin
      dependent [3H]thymidine incorporation, indicating a reduction in DNA synthesis.
      Insulin-dependent [U-14C]glucose incorporation into cellular lipids was also
      significantly reduced in C2 cell line suggesting an alteration in lipogenesis. In
      wild type LMH cells, SHC which is involved in Ras pathway, also served as a
      substrate for insulin receptor tyrosine kinase. In C2 cells, SHC expression, its
      association with the insulin receptor and its tyrosine phosphorylation were
      largely increased. Two forms of the regulatory subunit of PI 3-kinase were
      present: p85 and p55 forms. Furthermore, C2 cells displayed increased basal
      phosphatidylinositol (PI) 3'-kinase activity. This report demonstrates a role for
      cIRS-1 in the metabolic and mitogenic actions of insulin in LMH cells. However,
      the overexpression of cIRS-1 antisense did not completely abolish cell
      proliferation. This may be explained by the exacerbation of an alternative
      pathway that only partly compensate for the knocking out of cIRS-1 gene: the
      overexpression of SHC.

PMID- 9605521
TI  - Prolactin induces expression of FGF-2 and a novel FGF-responsive NonO/p54nrb
      related mRNA in rat lymphoma cells.
AB  - The rat Nb2-11C lymphoma cell line expresses high affinity prolactin (PRL)
      receptors, and requires lactogenic hormones for survival and proliferation. We
      have applied differential display to identify genes which are differentially
      induced in Nb2-11C cells following PRL stimulation, or which are constitutively
      expressed in the PRL-independent Nb2-Sp cells. In the present study we
      characterized a clone (22c.2) which was expressed in Nb2-Sp cells, and in Nb2-11C
      cells given PRL for 3 h but not in untreated cells. The 279 bp cDNA had 95%
      homology with the 3' end of the murine 2.6 kb FGF-inducible gene 14 (FIN14). When
      clone 22c.2 was used to screen a Nb2-Sp cDNA library to obtain a longer cDNA, a
      unique 1039 bp clone PNR (Prolactin-responsive/ NonO-Related) was isolated,
      subcloned and sequenced. The deduced amino acid sequence encoded by the PNR open
      reading frame had significant homology with a family of RNA- and DNA-binding
      proteins which include the human polypyrimidine tract-binding protein (PTB)
      associated splicing factor (PSF), the murine non-POU-domain-containing octamer
      binding protein (NonO) and the human NonO homologue p54nrb. Nb2-11C cells
      expressed three PNR-related mRNA transcripts of 2.5, 3.0 and > 10 kb. Expression
      of the 2.5 and 3.0 kb transcripts were increased at least 4-fold within 3 h of
      PRL treatment. PNR expression was also significantly stimulated within 3 h by
      addition of FGF-2 to either Nb2-11C or Nb2-Sp cells, although alone FGF-2 was not
      mitogenic for either cell line. Reverse transcription-polymerase chain reaction
      (RT-PCR) confirmed the expression of both FGF-2 and FGF receptor mRNA in Nb2
      cells. raising the possibility of an autocrine or paracrine function for FGF-2 in
      lymphoma cells. Furthermore, PRL rapidly stimulated the expression of FGF-2 mRNA
      in a time- and dose-dependent manner in both Nb2-11C and Nb2-Sp cells. FGF-2
      expression was increased within 1 h and was maintained at a high level for at
      least 10 h following treatment with 2 ng/ml PRL. Western blotting with anti-FGF2
      antisera demonstrated PRL stimulation of intracellular accumulation, but not
      secretion of immunoreactive FGF-2. The observation of PRL-responsive expression
      of FGF-2 in Nb2 cells suggests a previously unrecognized pathway for PRL action
      in lymphoid cells.

PMID- 9605522
TI  - Saccade-induced activity of dorsal lateral geniculate nucleus X- and Y-cells
      during pharmacological inactivation of the cat pretectum.
AB  - The influence of neurons projecting from the pretectal nuclear complex to the
      ipsilateral dorsal lateral geniculate nucleus (LGNd) was investigated in awake
      cats. Responses from relay cells in the A-laminae of the LGNd were
      extracellularly recorded and analyzed during saccadic eye movements and visual
      stimulation in association with reversible inactivation of the ipsilateral
      pretectum with the GABA agonist, muscimol. Pretectal inactivation (PTI) resulted
      in spontaneous nystagmic eye movements in the dark with slow phases directed away
      from the injected side. In the control situation, all Y-cells and about two
      thirds of X-cells were excited during saccades or saccade-like visual stimulation
      but one third of X-cells were inhibited. During PTI all recorded X-cells were
      inhibited, either during saccades or saccade-like visual stimulation. The PTI
      associated inhibition was stronger than in inhibited X-cells in control
      experiments only during saccades but not during stimulation with a moving pattern
      while the eyes were stationary. In Y-cells a reduction in the response peak width
      at half-height was seen during PTI, again only during saccades but not during
      stimulation with a moving pattern. These results indicate that during saccades
      the pretecto-geniculate pathway has a stronger influence on X LGNd relay cells
      than on Y-cells. The findings are discussed in terms of saccadic suppression and
      postsaccadic facilitation.

PMID- 9605523
TI  - Role of the low-affinity NGF receptor (p75) in survival of retinal bipolar cells.
AB  - We have examined the role of neurotrophins in promoting survival of mammalian rod
      bipolar cells (RBC) in culture. Retinas taken from 8- to 10-day-old Long-Evans
      rats were dissociated and cultured in media supplemented with either nerve growth
      factor (NGF), neurotrophin-3 (NT-3), brain-derived neurotrophic factor (BDNF),
      ciliary neurotrophic factor (CNTF), or basic fibroblast growth factor (FGF-2).
      Survival was measured by the number of cells that were immunoreactive for alpha-,
      beta-, gamma-PKC, a bipolar cell-specific marker. Compared to untreated cultures,
      CNTF had no effect on RBC survival, while NGF and NT-3 increased survival only
      slightly. BDNF, however, increased survival by approximately 300%. Similar
      results were obtained with FGF-2. Both nerve growth factor (NGF) and an antibody
      (anti-REX) which interferes with binding to the 75-kD low-affinity neurotrophin
      receptor (p75NTR) eliminated BDNF-promoted survival, but had no effect on FGF-2
      mediated survival. Interestingly, p75NTR was expressed by retinal glia (Muller
      cells), but not by the bipolar cells themselves, providing for the possibility
      that BDNF might induce Muller cells to produce a secondary factor, perhaps FGF-2,
      which directly rescues RBCs. In support of this hypothesis, an antibody that
      neutralizes FGF-2 attenuated the trophic effects of BDNF, and dramatically
      reduced survival in cultures with no added growth factors, indicating that there
      may be an endogenous source of FGF-2 that promotes survival of RBCs in culture.
      We suggest that BDNF increases production or release of FGF-2 by binding to
      p75NTR on Muller cells.

PMID- 9605524
TI  - Responses of ganglion cells to contrast steps in the light-adapted retina of the
      tiger salamander.
AB  - The impulse discharge of single ganglion cells was recorded extracellularly in
      superfused eyecup preparations of the tiger salamander (Ambystoma tigrinum).
      Contrast flashes (500 ms) were applied at the center of the receptive field while
      the retina was light adapted to a background field of 20 cd/m2. The incidence of
      cell types in a sample of 387 cells was: ON cells (4%), OFF cells (28%), and
      ON/OFF cells (68%). Quantitative contrast/response measurements were obtained for
      83 cells. On the basis of C50, the contrast necessary to evoke a half-maximal
      response, ON/OFF cells fell into 3 groups: (1) Positive Dominant (26%), (2)
      Balanced (23%), and (3) Negative Dominant (51%). Positive Dominant cells tended
      to be relatively contrast insensitive. On the other hand, many Negative Dominant
      cells showed remarkably low C50 values and very steep contrast/response curves.
      Contrast gain to negative contrast averaged 8.5 impulses/s/% contrast, some four
      times greater than that evoked by positive contrast. In most ON/OFF cells, the
      latency of the first spike evoked by a negative contrast step was much shorter
      (40-100 ms) than that evoked by a positive contrast step of equal contrast. OFF
      cells typically showed higher C50 values, larger dynamic ranges, and longer
      latencies than those of Negative Dominant ON/OFF cells. Thus, different pathways
      or mechanism apparently mediate the off responses of OFF and ON/OFF cells. In
      sum, the light-adapted retina of the tiger salamander is strongly biased in favor
      of negative contrast, as shown by the remarkably high contrast sensitivity and
      faster response of Negative Dominant cells, the remarkably low incidence of ON
      cells, and the insensitivity of Positive Dominant cells. Some possible underlying
      influences of bipolar and amacrine cells are discussed.

PMID- 9605525
TI  - Response latencies of cells in the cat's lateral geniculate nucleus are less
      variable during burst than tonic firing.
AB  - We measured the variability in latency of the first spike seen in cells of the
      cat's lateral geniculate nucleus following the onset of a visual stimulus. We
      found that, in each of the 11 cells tested, this variability was significantly
      lower during burst than during tonic firing. We suggest that this difference
      confers an advantage in signal detection during burst compared to tonic firing.
      This complements other reported advantages of burst firing for signal detection
      seen in signal-to-noise ratios and in the ability to efficiently drive
      postsynaptic cells.

PMID- 9605526
TI  - Laminar differences in the spatiotemporal structure of simple cell receptive
      fields in cat area 17.
AB  - Previous studies of cat visual cortex have shown that the spatiotemporal (S-T)
      structure of simple cell receptive fields correlates with direction selectivity.
      However, great heterogeneity exists in the relationship and this has implications
      for models. Here we report a laminar basis for some of the heterogeneity. S-T
      structure and direction selectivity were measured in 101 cells using stationary
      counterphasing and drifting gratings, respectively. Two procedures were used to
      assess S-T structure and its relation to direction selectivity. In the first, the
      S-T orientations of receptive fields were quantified by fitting response temporal
      phase versus stimulus spatial phase data. In the second procedure, conventional
      linear predictions of direction selectivity were computed from the amplitudes and
      phases of responses to stationary gratings. Extracellular recording locations
      were reconstructed histologically. Among direction-selective cells, S-T
      orientation was greatest in layer 4B and it correlated well (r = 0.76) with
      direction selectivity. In layer 6, S-T orientation was uniformly low, overlapping
      little with layer 4B, and it was not correlated with directional tuning. Layer 4A
      was intermediate in S-T orientation and its relation (r = 0.46) to direction
      selectivity. The same laminar patterns were observed using conventional linear
      predictions. The patterns do not reflect laminar differences in direction
      selectivity since the layers were equivalent in directional tuning. We also
      evaluated a model of linear spatiotemporal summation followed by a static
      nonlinear amplification (exponent model) to account for direction selectivity.
      The values of the exponents were estimated from differences between linearly
      predicted and actual amplitude modulations to counterphasing gratings. Comparing
      these exponents with another exponent--that required to obtain perfect matches
      between linearly predicted and measured directional tuning--indicates that an
      exponent model largely accounts for direction selectivity in most cells in layer
      4, particularly layer 4B, but not in layer 6. Dynamic nonlinearities seem
      essential for cells in layer 6. We suggest that these laminar differences may
      partly reflect the differential involvement of geniculocortical and intracortical
      mechanisms.

PMID- 9605527
TI  - Regulation of cGMP-dependent current in On bipolar cells by calcium/calmodulin
      dependent kinase.
AB  - The metabotropic receptor mGluR6 is localized to the dendrites of On bipolar
      cells and mediates synaptic input from photoreceptors. The binding of glutamate
      to the receptor activates a phosphodiesterase (PDE), which then hydrolyzes cGMP.
      A nonselective cationic conductance, believed to be gated directly by cGMP, is
      turned off as a result of the fall in cGMP levels, and the cell hyperpolarizes.
      Here we present evidence for regulation of the conductance by an additional
      mechanism that it is independent of cGMP. Whole-cell recordings were obtained
      from On bipolar cells in slices of tiger salamander retina. Dialysis of cells
      with 1 microM KN-62 or 10 microM KN-93, two inhibitors of type II calmodulin
      dependent protein kinase (CaMKII), depressed cGMP-dependent currents. This
      depression persisted when hydrolysis of cGMP was prevented with IBMX, a broad
      spectrum PDE inhibitor, suggesting that CaMKII acts downstream from the PDE in
      the cascade. The depression of cGMP-dependent currents was probably not due to a
      direct interaction of the inhibitors with the channels as neither 1 microM KN-62
      or 10 microM KN-93 was found to have any effect on cyclic nucleotide-gated
      channels when applied directly to excised patches of rod outer segments. We
      propose that phosphorylation by CaMKII may be an important mechanism for
      regulating the cGMP-dependent conductance of On bipolar cells.

PMID- 9605528
TI  - Effects of bicarbonate versus HEPES buffering on measured properties of neurons
      in the salamander retina.
AB  - Electrophysiological studies of the isolated retina involve perfusing the tissue
      with a physiological Ringer's. Organic pH buffers such as HEPES have become
      increasingly popular in recent years because for many purposes they offer a
      convenient and reliable alternative to the more traditional bicarbonate/CO2. In
      this paper, however, we report that important functional properties of rods,
      bipolar cells, and horizontal cells in the salamander, Ambystoma tigrinum, are
      sensitive to the choice of buffer and, in the case of horizontal cells, that
      sensitivity is acute. In bicarbonate/CO2 Ringer's, the dark potential of the
      horizontal cell was typically near -50 mV and saturating light caused it to
      hyperpolarize to about -75 mV. On switching to HEPES-buffered Ringer's at the
      same pH, horizontal cells depolarized in darkness to about -20 mV, close to the
      chloride equilibrium potential, and the kinetics of their light responses
      changed. The cone-driven components of light responses increased in size relative
      to rod-driven components. Saturating lights still hyperpolarized the cells to -75
      mV, however. Horizontal cells, being coupled via gap junctions, form a syncytium
      and syncytial length constants, measured in bicarbonate/CO2 Ringer's, were
      generally in the range 150-225 microm. On switching to HEPES-buffered Ringer's,
      length constants increased substantially to 250-330 microm. All these changes
      were reversible. We discuss our findings within the context of the cell's ability
      to regulate its internal pH.

PMID- 9605529
TI  - Visual acuity losses in pigeons with lesions of the nucleus of Edinger-Westphal
      that disrupt the adaptive regulation of choroidal blood flow.
AB  - Choroidal blood flow (ChBF) in birds is regulated by a neural circuit whose
      components are the retina, the suprachiasmatic nucleus, the medial division of
      the Edinger-Westphal nucleus (EWM), the ciliary ganglion, and the choriod. We
      have previously shown that lesions of EWM appear to result in pathological
      alterations in the retina. To determine whether EWM lesions also lead to altered
      visual functions, we have examined the effects of EWM lesions on visual acuity in
      pigeons. Bilateral lesions of EWM were made electrolytically, and visual acuity
      for high-contrast, square-wave gratings was determined behaviorally about 1 year
      later and compared to that of a group of pigeons that had received sham lesions
      of EW about 1 year prior to acuity testing. Because lesions targeting EWM
      invariably resulted in damage to the adjoining lateral part of the Edinger
      Westphal nucleus (EWL), which controls pupillary constriction and accommodation,
      two additional control groups were studied. In one such control group, bilateral
      lesions in the area pretectalis (AP), which innervates the pupillary control part
      of EWL and thereby controls pupillary constriction, were made and the effects on
      visual acuity determined about 1 year later. In the second such control group,
      the effects of acute accommodative and pupillary dysfunction on acuity were
      studied in pigeons made cycloplegic. The accuracy of all lesions was later
      confirmed histologically. The mean acuities of birds with AP lesions (9.1+/-1.4
      cycles/deg) and sham lesions (7.1+/-1.5 cycles/deg) were not significantly
      different from normal, based on published normative data on pigeons. In contrast,
      pigeons with lesions that completely destroyed EW bilaterally showed visual
      acuity (2.7+/-0.1 cycles/deg) that was well below the acuity of the sham and AP
      lesion control groups. The acuity of the cycloplegic pigeons (4.8+/-0.3
      cycles/deg) and one pigeon with a nearly complete bilateral EWL but a unilateral
      EWM lesion (6.4 cycles/deg) indicated that only about half of the loss with a
      bilateral EW lesion could be attributed to accommodative dysfunction. Thus,
      bilateral destruction of EWM appears to have led to a loss in visual acuity. This
      conclusion suggests that disruption of adaptive neural regulation of ChBF may
      impair visual function. Destruction of EWM was, however, associated with damage
      to the somatic components of the oculomotor and trochlear nuclei. The possibility
      cannot be excluded that such damage also contributed to the acuity loss.

PMID- 9605530
TI  - Effect of early monocular enucleation upon ocular dominance columns and
      cytochrome oxidase activity in monkey and human visual cortex.
AB  - We examined cytochrome oxidase (CO) activity in striate cortex of four macaque
      monkeys after monocular enucleation at ages 1, 1, 5, and 12 weeks. These animal
      experiments were performed to guide our interpretation of CO patterns in
      occipital lobe specimens obtained from two children who died several years after
      monocular enucleation during infancy for tumor. In the macaques, the ocular
      dominance columns were labelled by injecting [3H]proline into the remaining eye.
      After enucleation at age 1 week, ocular dominance columns were eliminated in
      layer IVc(beta), resulting in a uniform pattern of autoradiographic label and CO
      staining. However, columns could still be seen in wet, unstained sections and
      with the Liesegang silver stain. Autoradiographs through layers IVc(alpha) and
      IVa showed residual, shrunken columns belonging to the missing eye, indicating
      that enucleation has less drastic effects in these layers. In the two human
      cases, enucleation at age 1 week also resulted in uniform CO staining in layer
      IVc. In the macaque after enucleation at age 5 weeks, ocular dominance columns
      belonging to the missing eye were severely narrowed, but still occupied 20% of
      layer IVc(beta). CO revealed wide, dark columns alternating with thin, pale
      columns in layer IVc(beta). The CO pattern and the columns labelled by
      autoradiography matched perfectly. After enucleation at age 12 weeks, only mild
      shrinkage of ocular dominance columns occurred. Enucleation at ages 1, 5, and 12
      weeks did not alter the pattern of thin-pale-thick-pale stripes in V2. The main
      findings from this study were that (1) CO histochemistry accurately labels the
      boundaries of columns in layer IVc(beta) of macaque striate cortex after early
      monocular enucleation, making it a suitable technique for defining the critical
      period for plasticity of ocular dominance columns in human striate cortex; (2)
      enucleation causes more severe shrinkage of ocular dominance columns than eyelid
      suture; (3) early monocular enucleation obliterates ocular dominance columns in
      layer IVcbeta, but their pattern remains visible in wet sections and with the
      Liesegang stain; and (4) enucleation does not affect CO staining in V2.

PMID- 9605531
TI  - Processing of first- and second-order motion signals by neurons in area MT of the
      macaque monkey.
AB  - Extrastriate cortical area MT is thought to process behaviorally important visual
      motion signals. Psychophysical studies suggest that visual motion signals may be
      analyzed by multiple mechanisms, a "first-order" one based on luminance, and a
      "second-order" one based upon higher level cues (e.g. contrast, flicker). Second
      order motion is visible to human observers, but should be invisible to first
      order motion sensors. To learn if area MT is involved in the analysis of second
      order motion, we measured responses to first- and second-order gratings of single
      neurons in area MT (and in one experiment, in area V1) in anesthetized, paralyzed
      macaque monkeys. For each neuron, we measured directional and spatio-temporal
      tuning with conventional first-order gratings and with second-order gratings
      created by spatial modulation of the flicker rate of a random texture. A minority
      of MT and V1 neurons exhibited significant selectivity for direction or
      orientation of second-order gratings. In nearly all cells, response to second
      order motion was weaker than response to first-order motion. MT cells with
      significant selectivity for second-order motion tended to be more responsive and
      more sensitive to luminance contrast, but were in other respects similar to the
      remaining MT neurons; they did not appear to represent a distinct subpopulation.
      For those cells selective for second-order motion, we found a correlation between
      the preferred directions of first- and second-order motion, and weak correlations
      in preferred spatial frequency. These cells preferred lower temporal frequencies
      for second-order motion than for first-order motion. A small proportion of MT
      cells seemed to remain selective and responsive for second-order motion. None of
      our small sample of V1 cells did. Cells in this small population, but not others,
      may perform "form-cue invariant" motion processing (Albright, 1992).

PMID- 9605532
TI  - Spectral and polarization sensitivity of photocurrents of amphibian rods in the
      visible and ultraviolet.
AB  - Photocurrents from isolated rods of adults and sub-adults of three species of
      amphibians, Rana pipiens, Ambystoma tigrinum, and Xenopus laevis, were measured
      with suction pipette electrodes. The intensity for a half-maximal response was
      0.91+/-0.48 photons microm(-2) flash(-1) (mean +/- S.D., 10-ms flashes) for Rana,
      0.92+/-0.44 for Ambystoma, and 6.14+/-1.33 for Xenopus. The mean number of
      photoisomerizations at half-saturation was 22+/-12 for Rana, 50+/-24 for
      Ambystoma, and 221+/-48 for Xenopus. The photocurrent per photoisomerization is
      several times smaller in Xenopus rods than in the other two species. Spectral
      sensitivity was measured from 277-737 nm with light polarized both parallel and
      perpendicular to the planes of the membrane disks. Dichroism fell in the near UV
      and was absent in the region of absorption by tryptophan and tyrosine. Maximum
      sensitivity of Rana was at 503.9+/-2.6 nm (n = 86), and of Ambystoma, 505.8+/-1.8
      nm (n = 24). Animals from these same batches that were sampled by HPLC had no 3
      dehydroretinal (retinal2). Xenopus containing about 94% retinal2 and 6% retinal1
      had lambda(max) at 519.3+/-2.7 nm (n = 11). Spectral position of the beta-band,
      estimated by the method of Stavenga et al. (1993), appears to be at longer
      wavelengths in amphibian photoreceptors than in other vertebrates. Fits of log
      sensitivity to a normalized-frequency template that tracks the long-wavelength
      tail of the alpha-band (Lamb, 1995) show that the rod pigments of Rana and
      Ambystoma are slightly narrower than those found in the photoreceptors of fish
      and mammals.

PMID- 9605533
TI  - The selective impairment of the perception of first-order motion by unilateral
      cortical brain damage.
AB  - First-order (Fourier) motion consists of stable spatiotemporal luminance
      variations. Second-order (non-Fourier) motion consists instead of spatiotemporal
      modulation of contrast, flicker, or spatial frequency. In spite of extensive
      psychophysical and computational analysis of the nature and relationship of these
      two types of motion, it remains unclear whether they are detected by the same
      mechanism or whether separate mechanisms are involved. Here we report the
      selective impairment of first-order motion, on a range of local and global motion
      tasks, in the contralateral visual hemifield of a patient with unilateral brain
      damage centered on putative visual areas V2 and V3 in the medial part of the
      occipital lobe. His perception of second-order motion was unimpaired. As his
      disorder is the obverse of that reported after damage in the vicinity of human
      visual area MT (V5), the results support models of motion processing in which
      first- and second-order motion are, at least in part, computed separately at the
      extrastriate cortical level.

PMID- 9605534
TI  - The thalamo-hyperstriatal system is established by the time of hatching in chicks
      (Gallus gallus): a cholera toxin B subunit study.
AB  - Connections of the thalamo-hyperstriatal system of hatchling chicks were
      investigated using multiple injections of cholera toxin B subunit (CTb) in the
      wulst. In the diencephalon, cells with CTb-like immunoreactivity (CTb-LI) were
      seen bilaterally in n. dorsolateralis anterior thalami, pars lateralis dorsalis
      and ventralis, n. dorsolateralis anterior thalami, pars magnocellularis, and pars
      lateralis rostralis. Within this complex, more CTb-LI cells were observed in the
      ventral portions of the ipsilateral side, whereas more labeled cells were found
      in the dorsolateral portions of the contralateral side. Moreover, CTb-LI cells
      were seen bilaterally in n. superficialis magnocellularis. In the nonvisual
      thalamic structures, numerous CTb-LI cells were seen in n. dorsolateralis
      anterior thalami, pars medialis and n. dorsolateralis posterior thalami. In the
      ventral thalamus, intense CTb-LI fibers/terminals were present in the external
      half of the external laminae of n. geniculatus lateralis, pars ventralis.
      Moderate to minor concentrations of fibrous labeling were found in n.
      intercalatus thalami and n. ventrolateral thalami. Moreover, efferent projections
      of the wulst were evident in the most ventral half of the optic tectum and the
      pretectal areas. The latter included n. pretectalis medialis, n. spiriformis
      medialis, n. principalis precommissuralis, n. lentiformis mesencephali, pars
      magnocellularis, and n. superficialis synecephali. Also, CTb-LI fibers were seen
      in n. basal optic root. The present study provides strong evidence that neuronal
      connections of the thalamo-hyperstriatal system are well established by the time
      of hatching. Additionally, efferent projections from the wulst to the
      diencephalic, mesencephalic, and pretectal structures are evident.

PMID- 9605535
TI  - V4 lesions in macaques affect both single- and multiple-viewpoint shape
      discriminations.
AB  - The role of cortical area V4 in complex shape discriminations was studied by
      testing the effects of V4 lesions in macaques on the ability to visually
      discriminate between images of three-dimensional (3D) objects from different
      viewpoints. Stimuli were presented in pairs in the lower left or lower right
      visual field quadrants about 4 deg from the fovea, and the monkeys judged on each
      trial whether the two views were of the same or of different objects. Object
      similarity was varied to determine a threshold shape difference. V4 lesions
      caused profound, retinotopic, and apparently permanent disruptions of
      discrimination, regardless of whether the images represented single or multiple
      viewpoints. In V4 lesioned portions of the visual field, monkeys could
      discriminate objects only when they differed much more grossly in shape than was
      true in control locations. These effects of the lesion were virtually identical
      for discriminations that had been learned before lesions were placed and for
      those learned afterwards. As in previous studies, V4 lesions elevated contrast
      thresholds by approximately a factor of two, but control observations showed that
      this was not the basis of the disruption of shape discrimination. Manipulation of
      cues to shape showed that in control locations, monkeys maintained excellent
      shape discrimination despite a variety of stimulus alterations, whereas in V4
      lesioned areas their performance was easily disrupted. This finding suggests that
      V4 may support visual shape discriminations by facilitating the use of multiple
      visual cues. However, the fact that single-viewpoint and multiple-viewpoint
      discriminations were similarly affected indicates that the disruption was not
      specific to 3D shape discrimination, but may apply to a variety of subtle
      discriminations.

PMID- 9605536
TI  - ON direction-selective ganglion cells in the rabbit retina: dendritic morphology
      and pattern of fasciculation.
AB  - ON direction-selective (DS) ganglion cells were identified by
      electrophysiological recordings in DAPI labeled, isolated rabbit retinas. Their
      responses to a flashing spot were sustained. Their responses to moving stimuli
      were strong in the preferred direction and weak in the null direction. Injection
      of the recorded cells with Lucifer yellow revealed that the cells had a distinct
      dendritic morphology, consistent with that described previously (Buhl & Peichl,
      1986; Amthor et al., 1989; Famiglietti, 1992a). When neighboring cells were
      injected, an extensive dendritic co-fasciculation was observed. The pattern of
      fasciculation restricts the possible synaptic connections of the ON DS cell.

PMID- 9605537
TI  - Morphology of human retinal ganglion cells with intraretinal axon collaterals.
AB  - Ganglion cells with intraretinal axon collaterals have been described in monkey
      (Usai et al., 1991), cat (Dacey, 1985), and turtle (Gardiner & Dacey, 1988)
      retina. Using intracellular injection of horseradish peroxidase and Neurobiotin
      in in vitro whole-mount preparations of human retina, we filled over 1000
      ganglion cells, 19 of which had intraretinal axon collaterals and wide-field,
      spiny dendritic trees stratifying in the inner half of the inner plexiform layer.
      The axons were smooth and thin (approximately 2 microm) and gave off thin (<1
      microm), bouton-studded terminal collaterals that extended vertically to
      terminate in the outer half of the inner plexiform layer. Terminal collaterals
      were typically 3-300 microm in length, though sometimes as long as 700 microm,
      and were present in clusters, or as single branched or unbranched varicose
      processes with round or somewhat flattened lobular terminal boutons 1-2 microm in
      diameter. Some cells had a single axon whereas other cells had a primary axon
      that gave rise to 2-4 axon branches. Axons were located either in the optic fiber
      layer or just beneath it in the ganglion cell layer, or near the border of the
      ganglion cell layer and the inner plexiform layer. This study shows that in the
      human retina, intraretinal axon collaterals are associated with a morphologically
      distinct ganglion cell type. The synaptic connections and functional role of
      these cells are not yet known. Since distinct ganglion cell types with
      intraretinal axon collaterals have also been found in monkey, cat, and turtle,
      this cell type may be common to all vertebrate retinas.

PMID- 9605538
TI  - Localization of gephyrin and glycine receptor subunit immunoreactivity in the
      rabbit retina.
AB  - Being utilized by over 40% of the amacrine cells, glycine is considered to be a
      major inhibitory neurotransmitter in the retinas of all vertebrate species
      examined. Localization of gephyrin, which is a 93-kD peripheral membrane glycine
      receptor-associated anchoring protein, has been used in several studies to
      identify the sites of glycinergic interactions in the retina and other regions of
      the central nervous system. Recent studies have shown that gephyrin colocalizes
      with GABA(A) receptors which, like those for glycine, are also inhibitory amino
      acid receptors usually associated with a chloride channel. In the present study,
      we have used two antibodies which recognize either gephyrin (mAb7a), or the alpha
      and beta subunits of the glycine receptor (mAb4a) in order to determine to what
      extent gephyrin is associated with glycine receptors in the mammalian retina.
      Single-label studies showed extensive punctate staining throughout most of the
      inner plexiform layer with each antibody. Double labeling showed that nearly 90%
      of the glycine receptor sites were also immunoreactive for gephyrin. However,
      nearly 60% of the total punctae immunoreactive for gephyrin were not stained for
      glycine receptors. This distinction was most pronounced in the most proximal
      inner plexiform layer where only 24% of the gephyrin-immunoreactive sites were
      glycine receptor positive. This study suggests that although most glycine
      receptors in the rabbit retina colocalize with the anchoring protein gephyrin, a
      significant proportion of the gephyrin-labeled sites are not associated with
      glycine receptors. In light of studies showing gephyrin association with GABA(A)
      receptor subunits, the localization of gephyrin may be indicative of chloride
      mediated inhibitory amino acid transmission in general and not solely that of
      glycinergic. Given several studies which show that bipolar cells express glycine
      receptors and respond to glycine but do not express gephyrin, the 10% of glycine
      receptors not colocalized with gephyrin shown in the present study may represent
      a subtype of glycine receptors found on bipolar cells which do not require
      gephyrin for the functional clustering of receptor subunits.

PMID- 9605539
TI  - A glial palisade delineates the ipsilateral optic projection in Monodelphis.
AB  - In developing marsupials, the path taken through the optic chiasm by
      ipsilaterally projecting retinal ganglion cells is complicated. Just prior to
      entry into the chiasm, ganglion cells destined for the ipsilateral optic tract
      separate from the remainder of axons by turning abruptly downwards to take a
      position in the ventral part of the optic nerve. In this report, it is shown that
      a discrete population of about 10-15 large glial cells transiently form a linear
      array across the prechiasmatic part of the optic nerve, precisely at this axon
      turning point. The distinct morphology of these cells and their novel location
      may reflect a specialized role in axon guidance.

PMID- 9605540
TI  - Effects of signal sequences on the secretion of hen lysozyme by yeast:
      construction of four secretion cassette vectors.

PMID- 9605541
TI  - Structural studies on an inhibitory antibody against Thermus aquaticus DNA
      polymerase suggest mode of inhibition.
AB  - TP7, an antibody against Thermus aquaticus DNA polymerase I (TaqP), is used as a
      thermolabile switch in 'hot start' variations of PCR to minimize non-specific
      amplification events. Earlier studies have established that TP7 binds to the
      polymerase domain of TaqP, competes with primer template complex for binding and
      is a potent inhibitor of the polymerase activity of TaqP. We report
      crystallographic determination of the structure of an Fab fragment of TP7 and
      computational docking of the structure with the known three-dimensional structure
      of the enzyme. Our observations strongly suggest that the origin of inhibitory
      ability of TP7 is its binding to enzyme residues involved in DNA binding and
      polymerization mechanism. Although criteria unbiased by extant biochemical data
      have been used in identification of a putative solution, the resulting complex
      offers an eminently plausible structural explanation of biochemical observations.
      The results presented are of general significance for interpretation of docking
      experiments and in design of small molecular inhibitors of TaqP, that are not
      structurally similar to substrates, for use in PCR. Structural and functional
      similarities noted among DNA polymerases, and the fact that several DNA
      polymerases are pharmacological targets, make discovery of non-substrate based
      inhibitors of additional importance.

PMID- 9605542
TI  - Recurrence quantification analysis in structure-function relationships of
      proteins: an overview of a general methodology applied to the case of TEM-1 beta
      lactamase.
AB  - Protein structure-function relationships have been increasingly scrutinized by a
      variety of correlational and information theoretic measures. In an effort to
      extend this methodology, a technique originally developed in non-linear science,
      recurrence quantification analysis, was combined with traditional principal
      components analysis to study a large number (56) of TEM-1 beta-lactamase mutants.
      The hydrophobicity profiles corresponding to the primary structure of 13
      naturally occurring mutations partially impairing function, together with 43
      artificial non-tolerated mutations were subjected to discriminant analysis,
      derived from the results of recurrence quantification analysis, coupled to a
      principal exponents extraction. Eleven (85%) of the naturally occurring mutants
      and 36 (84%) of the artificial mutants were correctly classified (p < 0.0001). We
      conclude that this technique may be useful in protein engineering and, in
      general, in structure-function studies of biopolymers.

PMID- 9605543
TI  - A molecular mechanism for toxin block in N-type calcium channels.
AB  - A series of highly toxic snail venoms, the omega-conotoxins, have been shown to
      bind selectively, and often irreversibly to the N-type voltage-gated calcium
      channel alpha-1 subunit. The most potent of these is known as omega-conotoxin
      GVIA from the species Conus geographus, a marine snail that has been responsible
      for a number of human fatalities. Using theoretical techniques we present a
      plausible binding model of the conotoxin to a loop region of the channel. Our
      model of the toxin binding region also contains a possible EF-hand motif and we
      suggest that this Ca2+ binding domain lies on the ion permeation pathway, a
      possible Ca2+ recruitment site.

PMID- 9605545
TI  - Engineering subtilisin YaB: restriction of substrate specificity by the
      substitution of Gly124 and Gly151 with Ala.
AB  - The 3-D structure of subtilisin YaB was computer modelled using the structures of
      subtilisin BPN', subtilisin Carlsberg and thermitase as templates. Gly124 and
      Gly151 located on both sides of the waist of the S1 pocket were selected for site
      directed mutagenesis based on the modelled structure. The mutated ale genes
      coding for the mutant subtilisin YaB were expressed in Bacillus subtilis DB104.
      All of the G124 and G151 series of mutants exhibited an increase of relative
      catalytic activity for elastin-orcein against casein and myofibrillar proteins.
      The S1 substrate specificity of G124A, G124V and G151A mutants were assessed
      using various carbobenzoxy-amino acid-nitrophenyl esters and succinyl-Ala-Ala
      (Pro or Val)-(Ala, Phe or Leu)-p-nitroanilide [AA(P/V) (A/F/L)]. While G124A and
      G124V mutants hydrolyzed only Ala and Gly esters, G151A mutant hydrolyzed Ala,
      Leu and Gly esters. The G124A and G124V mutants did not hydrolyze AAPF and AAPL.
      However, these two mutants hydrolyzed AAPA and AAVA with kcat/Km values
      approximately 3-10-fold higher than those of the wild-type enzyme. The G151A
      mutant did not hydrolyze AAPF, but hydrolyzed AAPL, AAPA and AAVA with kcat/Km
      values approximately 1-4-fold higher than those of the wild-type enzyme. These
      results clearly indicate that the S1 substrate specificity of G124A and G124V
      mutants was restricted to Ala and Gly, and G151A mutant to Ala, Gly and Leu.

PMID- 9605544
TI  - The role of Glu259 in Escherichia coli elongation factor Tu in ternary complex
      formation.
AB  - Determination of the crystal structure of the ternary complex formed between
      elongation factor Tu:GTP and aminoacylated tRNA revealed three regions of
      interaction between elongation factor Tu and tRNA. The structure indicates that
      the conserved glutamic acid at position 271 in Thermus aquaticus EF-Tu could be
      involved in the binding of the 3' CCA-Phe end of the aminoacylated tRNA.
      Therefore, the corresponding residue, Glu259, of Escherichia coli EF-Tu was
      mutated into alanine, aspartic acid, glutamine and tyrosine, in order to
      substantiate the crystallographic structural evidence and to obtain further
      knowledge of the importance of this residue. All of the mutated proteins showed
      nucleotide binding properties similar to the wild type. In addition the GTPase
      activities were similar to the wild type. The mutation of Glu259 to either
      alanine or aspartic acid resulted in a reduced strength of interaction with tRNA,
      while mutation to tyrosine abolished completely the interaction with tRNA.
      Finally, mutation to glutamine resulted in an elongation factor Tu variant
      behaving like the wild type. In conclusion, the environment around the site
      binding the CCA-Phe end of the tRNA is very restricted spatially and chemically
      so that only a residue with almost the same size and chemical properties as
      glutamic acid fulfils the requirements with regard to size, salt bridge-formation
      potential and maintenance of the backbone conformation at the 259 position.

PMID- 9605546
TI  - Mutations to alter Aspergillus awamori glucoamylase selectivity. I. Tyr48Phe49-
      >Trp, Tyr116-->Trp, Tyr175-->Phe, Arg241-->Lys, Ser411-->Ala and Ser411-->Gly.
AB  - Glucoamylase mutations to reduce isomaltose formation from glucose condensation
      and thus increase glucose yield from starch hydrolysis were designed to produce
      minor changes in the active site at positions not totally conserved. Tyr175-->Phe
      and Ser411-->Gly glucoamylases had catalytic efficiencies on DP 2-7
      maltooligosaccharides like those of wild-type glucoamylase, while the catalytic
      efficiencies of Tyr116-->Trp, Arg241-->Lys and Ser411-->Ala glucoamylases were
      reduced by about half and Tyr48Phe49-->Trp glucoamylase had little remaining
      activity. Tyr175-->Phe, Ser411-->Ala and Ser411-->Gly glucoamylases had decreased
      ratios of the initial rate of isomaltose formation from glucose condensation to
      that of glucose formation from maltodextrin hydrolysis at both 35 and 55 degrees
      C compared with wild-type glucoamylase. Arg241-->Lys glucoamylase had a very
      similar ratio, while Tyr116-->Trp glucoamylase had a higher ratio. The highest
      glucose yields from maltodextrin hydrolysis were by the mutant glucoamylases
      having the lowest ratios of initial rates of isomaltose formation to glucose
      formation and this predicted high glucose yields better than the ratio of
      catalytic efficiency for maltose hydrolysis to that for isomaltose hydrolysis.

PMID- 9605547
TI  - Mutations to alter Aspergillus awamori glucoamylase selectivity. II. Mutation of
      residues 119 and 121.
AB  - Mutations Ser119-->Glu, Ser119-->Gly, Ser119-->Trp, Gly121-->Ala and Gly121-
      >Ala/Ser411-->Gly were constructed in glucoamylase to change substrate
      specificity. Mutation Ser411-->Gly was already known to decrease glucoamylase
      selectivity toward isomaltose formation and to increase peak glucose yield. All
      mutated glucoamylases had slightly lower specific activities on maltose than on
      wild-type glucoamylase. Ser119-->Glu, Ser119-->Gly and Ser119-->Trp glucoamylases
      were about as active on isomaltose and DP 4-7 maltooligosaccharides as wild-type
      glucoamylase. Gly121-->Ala and Gly121-->Ala/Ser411-->Gly glucoamylases were less
      active. At 55 degrees C Ser119-->Glu, wild-type, Ser119-->Trp, Ser119-->Gly,
      Gly121-->Ala and Gly121-->Ala/Ser411-->Gly glucoamylases had progressively higher
      peak glucose yields, generally in the opposite order to their activities. There
      was also an inverse correlation between peak glucose yield and ratio of initial
      rate of isomaltose production from glucose condensation to that of glucose
      production from maltodextrin hydrolysis. The effect of mutations Gly121-->Ala and
      Ser411-->Gly was not additive in predicting the effect of the double mutation on
      the ratio or on peak glucose yield.

PMID- 9605548
TI  - Pancreatic lipase-related protein type I: a specialized lipase or an inactive
      enzyme.
AB  - The existence of pancreatic lipase-related protein 1 (PLRP1) in vertebrates has
      been postulated based on the screening of pancreatic cDNA libraries from
      different species. In this paper, we report the presence of variable amounts of
      PLRP1 relative to colipase-dependent lipase (PL) in adults from several species.
      Only a very low lipase activity could be detected for native or recombinant PLRP1
      using a large variety of substrates and conditions. Interestingly, this activity
      is dependent on the presence of bile salts and colipase and PLRP1 is shown to
      possess the same affinity as PL for colipase. Modelling investigations revealed
      some interesting differences between PLRP1 and PL, notably concerning
      substitutions in the C-terminal domain which might affect the bending motion of
      this domain relative to the N-terminal domain in PLRP1. The potential impact of
      these differences on the lack of lipase activity of PLRP1 was investigated using
      chimeric proteins designed by C-terminal domain exchange between dog PLRP1 and
      horse PL. Analysis of the catalytic properties of the chimera clearly indicated
      that the C-terminal domain exchange neither inactivates the horse enzyme nor
      results in an active dog PLRP1. From these findings, it can be concluded that the
      PLRP1 C-terminal domain is fully functional with respect to colipase binding. The
      lack of lipase activity or the still undetermined function of PLRP1 is likely to
      result mainly from particular features of the N-terminal domain.

PMID- 9605549
TI  - Engineering the steroid-specificity of an anti-17beta-estradiol Fab by random
      mutagenesis and competitive phage panning.
AB  - We have employed random mutagenesis and phage display to improve the steroid
      specificity of an anti-17beta-estradiol Fab fragment. The VH domain was mutated
      using error-prone PCR; the mutation rate was controlled by adjusting the number
      of effective duplications. A phage library of 2 x 10(6) independent mutants was
      generated, each mutant containing on average 24 amino acid changes. We selected
      for decreased testosterone (TES) cross-reactivity by adding a large excess TES as
      a competitor to the panning reactions. After four panning rounds, the cross
      reactivities of the individual mutant clones ranged from 19 to 4%, showing up to
      20-fold improvement over the original value (78%). Estradiol affinities were
      mainly unchanged. Sequencing of the VH regions revealed two hot spots, one
      located around Ser32 in CDR1 and the other around Thr52A in CDR2, while no
      mutations were found in CDR3. Although most clones had multiple mutations, it was
      possible to deduce the residues relevant to the improved specificity by comparing
      the sequences and binding data of the mutants. We demonstrated that controlled
      error-prone PCR mutagenesis is a rapid method to identify such key residues,
      lending itself to the scanning of 'lead' positions for further mutagenesis by
      other methods.

PMID- 9605550
TI  - Enhancement of opioid inhibition of GABAergic synaptic transmission by cyclo
      oxygenase inhibitors in rat periaqueductal grey neurones.
AB  - Cyclo-oxygenase (COX) inhibitors potentiate opioid inhibition of GABAergic
      synaptic transmission in rat periaqueductal grey (PAG) (Vaughan et al., 1997). In
      the present study, the relative contribution of cyclo-oxygenase-1 (COX-1) and COX
      2 inhibition to this phenomenon was examined by use of whole-cell patch clamp
      recordings in brain slices. The mu-receptor partial agonist morphine (10 microM)
      had little effect on GABAergic synaptic transmission. Morphine reduced the
      frequency of spontaneous miniature inhibitory postsynaptic currents (m.i.p.s.cs)
      by 13%. The nonselective COX inhibitor, indomethacin, produced a dose-dependent
      potentiation of the morpine inhibition of m.i.p.s.c. frequency (maximum
      inhibition 42%, IC50=6 nM). More selective COX-2 inhibitors produced a similar
      potentiation of the morphine inhibition of m.i.p.s.c. frequency; however, at
      greater concentrations (IC50=57 nM piroxicam, 1.7 microM DFU). Maintaining slices
      in the protein synthesis inhibitor cycloheximide (1 microM), to prevent COX-2
      induction, had no effect on the potentiation action of DFU (10 microM). These
      results demonstrate that the potentiation of opioid inhibition of GABAergic
      synaptic transmission in PAG is largely a result of inhibition of COX-1 activity.
      These findings suggest that COX-1, rather than COX-2 inhibition, mediates the
      synergistic analgesic actions of opioids and non-steroidal anti-inflammatory
      drugs (NSAIDs) in the midbrain PAG.

PMID- 9605551
TI  - The effect of a secreted form of beta-amyloid-precursor protein on intracellular
      Ca2+ increase in rat cultured hippocampal neurones.
AB  - 1. The effects of secreted forms of beta-amyloid-precursor proteins (APP(S)s) on
      the intracellular Ca2+ concentration ([Ca2+]i) were investigated in rat cultured
      hippocampal neurones. APP695S, a secretory form of APP695, attenuated the
      increase in [Ca2+]i evoked by glutamate. In addition, APP695S itself evoked an
      increase in [Ca2+]i in 1 or 2 day-cultured hippocampal cells, but not in 7 to 13
      day-cultured cells. 2. Eighty-one percent of neurones which were
      immunocytochemically positive for microtubule-associated protein 2 responded to
      APP695S with an increase in [Ca2+]i. 3. APP695S induced a transient rise in
      [Ca2+]i even in the absence of extracellular Ca2+ and produced an elevation in
      inositol-1,4,5-trisphosphate (IP3) in a concentration-dependent manner from 100
      to 500 ng ml(-1). In the presence of extracellular Ca2+, APP695S caused a
      transient rise in [Ca2+]i followed by a sustained phase at high [Ca2+]i,
      suggesting Ca2+ entry from the extracellular space. 4. The [Ca2+]i elevation was
      mimicked by amino terminal peptides of APPs, but not by carboxy terminal
      peptides. 5. These results taken together suggest that APP695S induces an
      increase in [Ca2+]i in hippocampal neurones through an IP3-dependent mechanism
      that changes according to the stage of development.

PMID- 9605552
TI  - Two imidazoquinoxaline ligands for the benzodiazepine site sharing a second low
      affinity site on rat GABA(A) receptors but with the opposite functionality.
AB  - 1. Imidazoquinoxaline PNU-97775 and imidazoquinoline PNU-101017 are
      benzodiazepine site ligands with a second low affinity binding site on GABA(A)
      receptors, the occupancy of which at high drug concentrations reverses their
      positive allosteric activity via the benzodiazepine site, and may potentially
      minimize abuse liability and physical dependence. 2. In this study we discovered,
      with two imidazoquinoxaline analogues, that the functionality of the second site
      was altered by the nitrogen substituent on the piperazine ring moiety: PNU-100076
      with a hydrogen substituent on the position produced a negative allosteric effect
      via the second low affinity site, like the parent compounds, while PNU-100079
      with a trifluoroethyl substituent produced a positive allosteric response. 3.
      These functional characteristics were monitored with Cl- currents measurements in
      cloned rat alphaxbeta2gamma2 subtypes of GABA(A) receptors expressed in human
      embryonic kidney 293 cells, and further confirmed in rat cerebrocortical
      membranes containing complex subtypes of GABA(A) receptors with binding of [35S]
      TBPS, which is a high affinity ligand specific for GABA(A) receptors with
      exquisite sensitivity to allosteric modulations. 4. This structure-functional
      relationship could be exploited to further our understanding of the second
      allosteric site of imidazoquinoxaline analogues, and to develop more effective
      benzodiazepine site ligands without typical side effects associated with those
      currently available on the market.

PMID- 9605553
TI  - Endothelial dysfunction and metabolic control in streptozotocin-induced diabetic
      rats.
AB  - 1. The aim of this work was to study the influence of the metabolic control,
      estimated by the levels of glycosylated haemoglobin in total blood samples
      (HbA1c), in developing vascular endothelial dysfunction in streptozotocin-induced
      diabetic rats. Four groups of animals with different levels of insulin treatment
      were established, by determining HbA1c values in 5.5 to 7.4%, 7.5 to 9.4%, 9.5 to
      12% and > 12%, respectively. 2. The parameters analysed were: (1) the endothelium
      dependent relaxations to acetylcholine (ACh) in isolated aorta and mesenteric
      microvessels; (2) the vasodilator responses to exogenous nitric oxide (NO) in
      aorta: and (3) the existence of oxidative stress by studying the influence of the
      free radical scavenger superoxide dismutase (SOD) on the vasodilator responses to
      both ACh and NO. 3. In both isolated aortic segments and mesenteric microvessels,
      the endothelium-mediated concentration-dependent relaxant responses elicited by
      ACh were significantly decreased when the vessels were obtained from diabetic
      animals but only with HbA1c values higher than 7.5%. There was a high correlation
      between HbA1c levels and the impairment of ACh-induced relaxations, measured by
      pD2 values. 4. The concentration-dependent vasorelaxant responses to NO in
      endothelium-denuded aortic segments were significantly reduced only in vessels
      from diabetic animals with HbA1c values higher than 7.5%. Again, a very high
      correlation was found between the HbA1c values and pD2 for NO-evoked responses.
      5. In the presence of SOD, the responses to ACh or NO were only increased in the
      segments from diabetic rats with HbA1c levels higher than 7.5%, but not in those
      from non-diabetic or diabetic rats with a good metabolic control (HbA1c levels
      <7.5%). 6. These results suggest the existence of: (1) a close relation between
      the degree of endothelial dysfunction and the metabolic control of diabetes,
      estimated by the levels of HbA1c; and (2) an increased production of superoxide
      anions in the vascular wall of the diabetic rats, which is also related to the
      metabolic control of the disease.

PMID- 9605554
TI  - The role of central melanocortin receptors in the activation of the hypothalamus
      pituitary-adrenal-axis and the induction of excessive grooming.
AB  - 1. In accord with previous studies intracerebroventricular (i.c.v.) injections of
      ACTH1-24 (1 microg) induced a display of excessive grooming, and increased the
      plasma concentrations of ACTH and corticosterone. Pituitary-adrenal activation
      was blocked by pretreatment with dexamethasone, indicating that the effect of the
      (i.c.v.) injected peptide was not caused by a peripheral effect on the adrenal
      cortex. 2. Doses of 1 and 3 microg of a non-selective melanocortin-3/4-receptor
      antagonist (SHU 9119), or of 5 and 10 microg of a selective melanocortin-4
      receptor antagonist ([D-Arg8]ACTH4-10), coadministered (i.c.v.) with 1 microg
      ACTH1-24, inhibited the ACTH1-24-induced activation of the hypothalamus-pituitary
      adrenal-axis and excessive grooming. 3. In addition, several doses of the
      selective melanocortin-3-receptor agonist Lys-gamma2-MSH were centrally
      administered, but neither neuroendocrine, nor excessive grooming responses were
      observed. 4. These results imply that the melanocortin-4-receptor, and not the
      melanocortin-3-receptor, is involved in the ACTH1-24-induced rise in plasma
      levels of ACTH and corticosterone, and excessive grooming.

PMID- 9605555
TI  - Ca2+ mobilization in the aortic endothelium in streptozotocin-induced diabetic
      and cholesterol-fed mice.
AB  - 1. Experiments were performed to compare Ca2+ mobilization in the aortic
      endothelium in streptozotocin (STZ)-induced diabetic and cholesterol-fed mice
      with that in age-matched controls. 2. The intracellular free Ca2+ ([Ca2+]i) in
      the fura PE-3 loaded endothelium of aortic rings was dose-dependently increased
      by cumulative administration of acetylcholine (ACh). ACh caused a transient rise
      in [Ca2+]i in Ca2+-free medium. The ACh-induced increase in [Ca2+]i in normal or
      Ca2+-free medium was significantly weaker in both STZ-induced diabetic and
      cholesterol-fed mice. 3. The weaker [Ca2+]i response in Ca2+-containing medium in
      STZ-induced diabetic and cholesterol-fed mice was normalized by chronic
      administration of cholestyramine. 4. The increased low density lipoprotein (LDL)
      levels seen in both STZ-induced diabetic and cholesterol-fed mice were normalized
      by the same chronic administration of cholestyramine (300 mg kg(-1), p.o. daily
      for 10 weeks). Chronic administration of cholestyramine had no effect on the
      plasma glucose level. 5. Lysophosphatidylcholine (LPC) decreased the [Ca2+]i
      responses to ACh in the aortic endothelium from normal mice. 6. These results
      suggest that ACh increases both Ca2+ influx and Ca2+ release from storage in the
      aortic endothelium. The weaker [Ca2+]i influx seen in the endothelium of aortae
      from both STZ-induced diabetic and cholesterol-fed mice was improved by the
      chronic administration of cholestyramine, and we suggest that this improvement is
      due, at least in part, to a lowering of the plasma LDL level. It is further
      suggested that LPC may have an important influence over Ca2+ mobilization in the
      endothelium.

PMID- 9605556
TI  - The adrenergic, cholinergic and NANC nerve-mediated contractions of the female
      rabbit bladder neck and proximal, medial and distal urethra.
AB  - 1. The nerve-mediated contraction of the female rabbit bladder neck and different
      portions of the urethra (proximal, medial and distal) was studied in vitro by
      electrical stimulation (50 V, 30 Hz, 0.05 ms width, trains of 5 s every 5 min) by
      use of a superfusion system. 2. The amplitude (Emax) and the duration (Dmax) of
      the stimulated contraction were studied in the four tissues. The Emax value was
      significantly higher in distal urethra (2.07+/-0.15 g) compared to the bladder
      neck (1.08+/-0.10 g), proximal urethra (0.73+/-0.07 g) and medial urethra (0.87+/
      0.07 g). In contrast, the Dmax value appeared slightly but significantly lower
      (P<0.05) in distal urethra (68.5+/-2.3 s) than in bladder neck (76.7+/-6.0 s),
      proximal urethra (84.5+/-5.0 s) and medial urethra (81.3+/-3.5 s). 3. Cocaine (1
      microM) significantly increased the basal Emax values in medial and distal
      urethra and the basal Dmax values in the four tissues. 4. Prazosin (1 microM)
      significantly reduced E max value in proximal, medial and distal urethra and Dmax
      value in bladder neck and proximal urethra. Atropine (1 microM) also
      significantly reduced Emax values in bladder neck and proximal urethra and
      reduced Dmax value in bladder neck, but not in other tissues. Yohimbine (0.1
      microM) was devoid of effect in the four tissues. 5. The association of prazosin
      (1 microM) and atropine (1 microM) did not modify the Emax and the Dmax values of
      the electrically-induced contractions, except in proximal urethra and in bladder
      neck where an additive inhibitory effect (on Emax only) was observed compared to
      prazosin and atropine alone. 6. The residual contractile response after combined
      treatment with prazosin and atropine was significantly diminished by tetrodotoxin
      (TTX; 1 microM) but not completely abolished. These NANC contractions were
      insensitive to P2X-purinoceptor desensitization by continuous tissue perfusion
      with alpha,beta-methylene ATP (30 microM). 7. These results demonstrate that
      bladder neck and proximal urethra are mainly innervated by the parasympathetic
      nervous system, whereas medial and distal urethras are to a greater extent under
      the control of the sympathetic innervation. The residual responses, insensitive
      to prazosin and atropine, may indicate a NANC innervation in the four tissues.
      However, the nature of the NANC neurotransmitter remains to be identified.

PMID- 9605557
TI  - Differential responses of pulmonary arteries and veins to histamine and 5-HT in
      lung explants of guinea-pigs.
AB  - 1. The mechanisms by which histamine and 5-HT differentially contract pulmonary
      arteries and veins are unclear. In lung explants from 26 guinea-pigs, we compared
      responses of pulmonary arteries and vein to histamine, 5-HT and KCI, and examined
      potential determinants for the differential responses. Lungs were filled with
      agarose, sectioned into approximately 1 mm thick slices, and vascular luminal
      areas measured by image analysis. 2. Histamine and 5-HT produced a concentration
      dependent constriction in arteries and veins, greater in the latter. KCl
      constricted arteries and veins equally. 3. The histamine H1 antagonist
      chlorpheniramine (10(-4) M) abolished contractions to histamine; the H2
      antagonist cimetidine enhanced maximal responses and sensitivity of arteries and
      veins to histamine, and diminished the differences between their maximal
      responses; the NO synthase inhibitor Nomega-nitro-L-arginine (L-NOARG) increased
      the maximal responses of arteries and veins, and the differences between their
      responses; indomethacin had no effect. 4. Contractions to 5-HT were abolished in
      arteries and markedly reduced in veins by the 5-HT2 antagonist ketanserin (10(-4)
      M); L-NOARG potentiated the maximal responses of arteries but not of veins;
      indomethacin increased the maximal responses of arteries but reduced them in
      veins. 5. By morphometry, arteries had a greater medial thickness and luminal
      diameter than veins. 6. The data suggest that in guinea-pigs, H2 receptors are
      responsible for the differential contractile responses of pulmonary arteries and
      veins to histamine, whereas endothelium-derived vasoactive substances are
      responsible for their differential contractile responses to 5-HT.

PMID- 9605558
TI  - Effect of melatonin in the rat tail artery: role of K+ channels and endothelial
      factors.
AB  - 1. The role of endothelial factors and potassium channels in the action of the
      pineal hormone melatonin to potentiate vasoconstrictor responses was investigated
      in the isolated perfused tail artery of the rat. 2. Melatonin (100 nM)
      potentiated contractile responses to both adrenergic nerve stimulation and alpha1
      adrenoceptor stimulation by phenylephrine. After removal of the endothelium,
      melatonin no longer caused potentiation. 3. The potentiating effect of melatonin
      was also lost when nitric oxide synthase was inhibited with L-NAME (10 nM). Thus
      potentiating effects depend on the presence of nitric oxide released by the
      endothelium. However, melatonin did not affect relaxation responses to
      acetylcholine in endothelium-intact arteries, nor did melatonin modulate relaxing
      responses to sodium nitroprusside in endothelium-denuded arteries. While
      melatonin does not appear to modulate agonist-induced release of nitric oxide nor
      its effect, melatonin may modulate nitric oxide production induced by flow and
      shear stress. 4. When the Ca2+-activated K+ channel opener, NS 1619 (10 microM),
      was present, potentiating effects of melatonin were restored in endothelium
      denuded vessels. However, addition of the opener of ATP-sensitive K+ channels,
      cromakalim (3 microM), did not have the same restorative effect. Furthermore,
      addition of a blocker of Ca2+-activated K+ channels, tetraethylammonium (1 mM),
      significantly attenuated potentiating effects of melatonin. These findings
      support the hypothesis that melatonin inhibits the activity of large conductance
      Ca2+-activated K+ channels to produce its potentiating effects. 5. Thus in the
      rat perfused tail artery, potentiation of constriction by melatonin depends on
      the activity of both endothelial factors and Ca2+-activated K+ channels. Our
      findings suggest that melatonin inhibits endothelial K+ channels to decrease flow
      induced release of nitric oxide as well as block smooth muscle K+ channels to
      enhance vascular tone.

PMID- 9605559
TI  - Age and region-dependent contraction to alpha-adrenoceptor agonists in rat and
      guinea-pig isolated trachea.
AB  - 1. The influence of age and of region on alpha-adrenoceptor-mediated contraction
      to (-)-adrenaline and (-)-noradrenaline was examined in rat (4-136 weeks) and
      guinea-pig (2-156 weeks) isolated tracheal ring preparations with particular
      emphasis on the early (up to 12 weeks) maturation phase. 2. In rat tracheal
      rings, significant regional variation was observed with respect to maximal (-)
      adrenaline-induced contraction, such that the greatest activity was seen in ring
      preparations from the laryngeal end of the trachea. Tracheal rings from the
      carinal end responded very poorly or were unresponsive to (-)-adrenaline,
      depending on animal age. These regional differences were seen across the age
      range. The potencies of (-)-adrenaline and (-)-noradrenaline remained unchanged
      with respect to animal age, but the maximum contractile tension that developed in
      response to these agonists increased with increasing animal age in all regions of
      the trachea. 3. In guinea-pig isolated tracheal tissue, maximum contractile
      responses (Emax) to (-)-adrenaline and (-)-noradrenaline remained unchanged with
      increasing animal age. In addition, there was no evidence for a region-dependence
      in the responsiveness of tracheal tissue to alpha-adrenoceptor-mediated
      contraction in this species. 4. In both guinea-pig and rat isolated tracheal
      tissue, alpha-adrenoceptor-mediated contraction appeared to involve the
      activation of alpha1-adrenoceptors.

PMID- 9605560
TI  - PYY-preferring receptor in the dorsal vagal complex and its involvement in PYY
      stimulation of gastric acid secretion in rats.
AB  - 1. Microinjection of peptide YY (PYY, 7-46 pmol) into the dorsal vagal complex
      (DVC) stimulated gastric acid secretion in urethane-anaesthetized rats. Using a
      variety of neuropeptide Y (NPY) and PYY derivatives, we characterized the
      pharmacological profile of the receptor mediating the acid secretory response to
      PYY. 2. [Pro34]rat(r)/porcine(p)PYY and [Pro34]human(h)PYY (23-117 pmol),
      microinjected unilaterally into the DVC resulted in a similar maximal increase in
      net acid secretion reaching 68+/-11 and 89+/-31 micromol 90 min(-1) respectively.
      3. Rat/hNPY and pNPY (47 pmol) microinjected into the DVC induced a similar net
      gastric acid secretion (27+/-8 and 23+/-8 micromol 90 min(-1) respectively) and a
      higher dose (116 pmol) tended to reduce the response. 4. Pancreatic polypeptide
      (PP, 4-46 pmol), [Leu31,Pro34]r/hNPY (47 and 117 pmol) and the Y2 selective
      agonists, hPYY3-36, pNPY5-36 and PNPY13-36 (25-168 pmol) microinjected into the
      DVC failed to influence basal gastric acid secretion. 5. The rank order of
      potency of PYY > or = [Pro34]r/pPYY = [Pro34]hPYY> r/hNPY = pNPY to stimulate
      gastric acid secretion upon injection into the DVC and the ineffectiveness of PP,
      [Leu31,Pro34]NPY and C-terminal NPY/PYY fragments suggest that a PYY-preferring
      receptor subtype may be involved in mediating the stimulating effect.

PMID- 9605561
TI  - Preservation of vascular function in rat mesenteric resistance arteries following
      cold storage, studied by small vessel myography.
AB  - 1. The use of isolated blood vessels to investigate the physiological and
      pharmacological control of the vasculature is limited by the requirement to use
      freshly isolated vessels. Hence, the aim of this study was to determine whether
      vascular smooth muscle and endothelial cell function could be preserved in
      resistance arteries by storing them in physiological salt solution (PSS) at 4
      degrees C. 2. Third order mesenteric resistance arteries (mean internal diameter
      237+/-6 microm) were dissected from the mesenteric bed of male Cob-Wistar rats.
      The vessel segments were mounted in a small vessel myograph for measurement of
      isometric tension, and equilibrated at their optimum resting force. Contractile
      responses to noradrenaline (NA; 1 x 10(-9) - 3 x 10(-5) M), phenylephrine (PE, 1
      x 10(-9)-3 x 10(-5) M), potassium chloride (KCI; 2.5-140 mM) and endothelin (ET
      1, 1 x 10(-11)-3 x 10(-7) M) and relaxant responses to acetylcholine (ACh; 1 x
      10(-9) - 3 x 10(-5) M) and 3-morpholinosydnonimine (SIN-1; 1 x 10(-9) - 1 x 10(
      4) M) were obtained in arteries, immediately after dissection (day 0) and
      following one to four days storage (day 1-day 4). 3. All arteries produced
      concentration-dependent contractions in response to each of the vasoconstrictors.
      There were no significant differences in the magnitude or sensitivity (pD2) of
      the vasoconstrictor responses between fresh and stored vessels. 4. Arteries
      precontracted with NA to approximately 80% of the maximum response, relaxed in a
      concentration-dependent manner in response to ACh and SIN-1. Vessel storage for
      up to three days resulted in no change in response to ACh or SIN-1. 5. Vessels
      analysed after four days of storage demonstrated a significant increase in
      sensitivity to ACh and SIN-1 (-logIC50 (M) values; ACh; day 0, 7.46+/-0.13 vs day
      4, 7.97+/-0.11, P<0.01 and SIN-1; day 0, 4.87+/-0.10 vs day 4, 5.52+/-0.08,
      P<0.01). There was also a significant increase in the maximum relaxant response
      to ACh after four days of storage (% relaxation; day 0, 92.65+/-2.84 vs day 4,
      100.36+/-0.36, P<0.05). 6. These results demonstrate that small resistance
      arteries remain viable if stored in PSS at 4 degrees C for up to four days, with
      no loss in endothelial cell function. The altered sensitivity to the vasodilators
      on day 4 suggests that vessels should only be stored for up to three days
      following dissection for analysis of functional responses.

PMID- 9605562
TI  - Characterization of 5-HT receptors mediating constriction of porcine carotid
      arteriovenous anastomoses; involvement of 5-HT1B/1D and novel receptors.
AB  - 1. It was previously shown that porcine cranial arteriovenous anastomoses (AVAs)
      constrict to 5-hydroxytryptamine (5-HT), ergotamine, dihydroergotamine, as well
      as sumatriptan and that sumatriptan acts exclusively via 5-HT1B/1D receptors. The
      present study was devoted to establish the contribution of 5-HT1B/1D receptors in
      the constriction of AVAs elicited by 5-HT (in presence of 0.5 mg kg(-1)
      ketanserin), ergotamine and dihydroergotamine in anaesthetized pigs. 2.
      Intracarotid infusion of 5-HT (2 microg kg(-1) min(-1)) and intravenous doses of
      ergotamine (2.5-20 microg kg(-1)) and dihydroergotamine (3-100 microg kg(-1))
      reduced AVA and increased nutrient blood flows and vascular conductances. The
      vasodilator response to 5-HT, observed mainly in the skin and ear, was much more
      prominent than that of the ergot alkaloids. 3. Treatment with the 5-HT1B/1D
      receptor antagonist GR127935 (0.5 mg kg(-1), i.v.) significantly attenuated both
      ergot-induced AVA constriction and arteriolar dilatation, whereas GR127935 only
      slightly affected the carotid vascular effects of 5-HT. 4. The results suggest
      that 5-HT constricts carotid AVAs primarily via receptors, which seem to differ
      from those (5-HT1B/1D) stimulated by sumatriptan. The ergot alkaloids produce AVA
      constriction for a substantial part via 5-HT1B/1D receptors, but also stimulate
      unidentified receptors. Both these non-5-HT1B/1D receptors may be targets for the
      development of novel antimigraine drugs. 5. The moderate vasodilator response to
      the ergot derivatives seems to be mediated, at least in part, by 5-HT1B/1D
      receptors, whereas the arteriolar dilatation caused by 5-HT may be mediated by
      other, possibly 5-HT7 receptors.

PMID- 9605563
TI  - Modulation by 5-HT1A receptors of the 5-HT2 receptor-mediated tachykinin-induced
      contraction of the rat trachea in vitro.
AB  - 1. In the Fisher 344 rat, tachykinins have been shown to cause the release of 5
      hydroxytryptamine (5-HT) from airway mast cells, which then causes direct smooth
      muscle activation as well as the release of acetylcholine from cholinergic
      nerves. The aim of the present study was to examine the modulatory effects of 5
      HT receptors on the neurokinin A (NKA)-induced release of endogenous 5-HT and
      airway smooth muscle contraction in the isolated Fisher 344 rat trachea. 2. The
      selective 5-HT2 receptor antagonist ketanserin (0.1 microM) produced an almost
      complete inhibition of the contractions caused by NKA (n=4, P<0.0001, two-way
      ANOVA), and a significant rightward shift of the concentration-response curve to
      5-HT (n=8, P<0.001, two-way ANOVA). 3. The partial agonist for 5-HT1A receptors,
      8-OH-DPAT (1 microM), and the full agonist for 5-HT1 receptors, 5-CT (0.3
      microM), potentiated the submaximal contractions induced by the 5-HT2 receptor
      agonist alpha-methyl-5-HT (0.1 microM) (n=4; P<0.005 and P<0.05, respectively). 8
      OH-DPAT (1 microM), as well as the 5-HT1A receptor antagonists pMPPI, SDZ 216525
      and NAN-190 (0.1 microM each), caused significant inhibition of the tracheal
      contractions induced both by NKA (10 nM-3 microM) and 5-HT (10 nM-10 microM) (n=4
      10). This suggests that activation of 5-HT1A receptors potentiates the 5-HT2
      receptor-mediated contractions. 4. SDZ 216525 (0.1 microM) significantly reduced
      the maximal contraction produced by 1 microM NKA (n=10, P< 0.001), without
      affecting the release of endogenous 5-HT. These data rule out the involvement of
      a 5-HT1A receptor-mediated positive feedback mechanism of the 5-HT release from
      mast cells. 5. Even in the presence of atropine (1 microM), 8-OH-DPAT (1 microM)
      further reduced the maximal NKA-induced contraction (n=4, P<0.0001), while the
      contractions of the rat isolated trachea induced by electrical field stimulation
      and the concentration-response curve to carbachol were unaffected by pMPPI (0.1
      microM), SDZ 216525 (0.1 microM), NAN-190 (0.1 microM) and 8-OH-DPAT (1 microM)
      (n=4-6). These data demonstrate that the 5-HT1A receptor-mediated potentiation of
      contractile responses is not due to nonspecific inhibition of airway smooth
      muscle contraction or to modulation of postganglionic nerve activation. 6. The
      selective 5-HT1B/1D receptor antagonist GR 127935, the selective 5-HT3 receptor
      antagonist tropisetron and the selective 5-HT4 receptor antagonists SB 204070 and
      GR 113808 (0.1 microM each) had no effect on the concentration-response curve for
      NKA (n=6-10), ruling out the involvement of 5-HT1B/1D, 5-HT3 and 5-HT4 receptors.
      7. The alpha-adrenoreceptor antagonist phentolamine (1 microM) had no effect on
      the 5-HT-induced contractions (n=4), ruling out the involvement of alpha
      adrenoreceptors. 8. In conclusion, the tachykinin-induced contraction of the F334
      rat isolated trachea is mediated by the stimulation of 5-HT2 receptors.
      Activation of 5-HT1A receptors located on airway smooth muscle potentiates the
      direct contractile effects of 5-HT2 receptor activation. The 5-HT1B/1D, 5-HT3 and
      5-HT4 receptors are not involved in the NKA-induced contraction of rat airways.

PMID- 9605564
TI  - Purinoceptor subtypes mediating contraction and relaxation of marmoset urinary
      bladder smooth muscle.
AB  - 1. The effects of adenosine triphosphate (ATP), adenosine diphosphate (ADP),
      alpha,beta-methylene-ATP (alpha,beta-MeATP) and 2-methylthio-ATP (2-MeSATP) on
      longitudinally orientated smooth muscle strips from marmoset urinary bladder were
      investigated by use of standard organ bath techniques. 2. After being mounted in
      superfusion organ baths, 66.7% (n=249) of marmoset detrusor smooth muscle strips
      developed spontaneous tone, 48.2% of all strips examined developed tone
      equivalent to greater than 0.1 g mg(-1) of tissue and were subsequently utilized
      in the present investigation. 3. On exposure to ATP, muscle strips exhibited a
      biphasic response, a rapid and transient contraction followed by a more prolonged
      relaxation. Both responses were found to be concentration-dependent. ADP and 2
      MeSATP elicited a similar response (contraction followed by relaxation), whereas
      application of alpha,beta-MeATP only produced a contraction. The potency order
      for each effect was alpha,beta-MeATP> >2-MeSATP> ATP>ADP (contractile response)
      and ATP=2-MeSATP> or = ADP> > alpha,beta-MeATP (relaxational response). 4.
      Desensitization with alpha,beta-MeATP (10 microM) abolished the contractile phase
      of the response to ATP, but had no effect on the level of relaxation evoked by
      this agonist. On the other hand, the G-protein inactivator, GDPbetaS (100 microM)
      abolished only the relaxation response to ATP. Suramin (general P2 antagonist,
      100 microM) shifted both the contractile and relaxation ATP concentration
      response curves to the right, whereas cibacron blue (P2Y antagonist, 10 microM)
      only antagonized the relaxation response to ATP. In contrast, the adenosine
      receptor antagonist, 8-phenyltheophylline (10 microM), had no effect on the
      relaxation response curve to ATP. 5. Incubation with tetrodotoxin (TTX, 3 microM)
      or depolarization of the muscle strip with 40 mM K+ Krebs failed to abolish the
      relaxation to ATP. In addition, neither Nomega-nitro-L-arginine (L-NOARG, 10
      microM) nor methylene blue (10 microM) had any effect on the relaxation response
      curve. However, tos-phe-chloromethylketone (TPCK, 3 microM), an inhibitor of
      cyclicAMP-dependent protein kinase A (PKA), significantly (P<0.01) shifted the
      curve for the ATP-induced relaxation to the right. 6. It is proposed that
      marmoset detrusor smooth muscle contains two receptors for ATP, a classical P2X
      type receptor mediating smooth muscle contraction, and a P2Y (G-protein linked)
      receptor mediating smooth muscle relaxation. The results also indicate that the
      ATP-evoked relaxation may occur through the activation of cyclicAMP-dependent
      PKA.

PMID- 9605565
TI  - Ribavirin uptake by human erythrocytes and the involvement of
      nitrobenzylthioinosine-sensitive (es)-nucleoside transporters.
AB  - 1. The major toxicity associated with oral therapy with ribavirin is anaemia,
      which has been postulated to occur as a result of accumulation of ribavirin
      triphosphate interfering with erythrocyte respiration. The objective of this
      study was to determine the mechanism by which ribavirin enters into erythrocytes.
      2. Entry into human erythrocytes was examined by measuring influx rates of [3H]
      ribavirin alone and with the inhibitor nitrobenzylthioinosine (NBMPR), and by
      investigating the inhibitory effects of nucleoside and nucleobase permeants on
      ribavirin transport, by use of inhibitor oil-stop methods. Transport mechanisms
      were further characterized by assessment of substrates to cause countertransport
      of ribavirin in preloaded erythrocytes, and by measuring the effects of ribavirin
      on [3H]-NBMPR binding to erythrocyte membranes. 3. Human erythrocytes had a
      saturable influx mechanism for ribavirin (Km at 22 degrees C of 440+/-100 microM)
      which was inhibited by nanomolar concentrations of NBMPR (IC50 0.99+/-0.15 nM).
      Nucleosides also inhibited the influx of ribavirin (adenosine more effective than
      uridine) but the nucleobases hypoxanthine and adenine had no effect. In addition,
      uridine caused the countertransport of ribavirin in human erythrocytes. Entry of
      ribavirin into horse erythrocytes, a cell type that lacks the NBMPR-sensitive
      (es) nucleoside transporter, proceeded slowly and via a pathway that was
      resistant to NBMPR inhibition. Ribavirin was a competitive inhibitor of adenosine
      influx (mean Ki 0.48+/-0.14 mM) and also inhibited NBMPR binding to erythrocyte
      membranes (mean Ki 2.2+/-0.39 mM). 4. These data indicate that ribavirin is a
      transported permeant for the es nucleoside transporter of human erythrocytes.
      There was no evidence for ribavirin entering cells via a nucleobase transporter.

PMID- 9605566
TI  - Serine-O-sulphate transport by the human glutamate transporter, EAAT2.
AB  - 1. Expression of the recombinant human excitatory amino aid transporters, EAAT1
      and EAAT2, in Xenopus laevis oocytes allows electrogenic transport to be studied
      under voltage clamp conditions. 2. We have investigated the transport of the
      pharmacological substrate, L-serine-O-sulphate transport by EAAT1 and EAAT2. The
      EC50 values for L-serine-O-sulphate transport by EAAT2 showed a steep voltage
      dependence, increasing from 152+/-11 microM at - 100 mV to 1930+/-160 microM at 0
      mV. In contrast to EAAT2, EC50 values for L-serine-O-sulphate transport by EAAT1
      were relatively constant over the membrane potential range of - 100 mV to 0 mV.
      The EC50 values for L-glutamate and D-aspartate transport, by EAAT2, were also
      relatively constant over this membrane potential range. 3. Chloride ions
      modulated the voltage-dependent changes in EC50 values for transport by EAAT2.
      This effect was most apparent for L-serine-O-sulphate transport, and to a lesser
      extent for L-glutamate and not at all for D-aspartate transport by EAAT2. 4.
      Extracellular sodium and proton concentrations also modulated the voltage
      dependence of L-serine-O-sulphate EC50 values for EAAT2. 5. We speculate that
      these different properties of L-serine-O-sulphate transport by EAAT2 compared to
      other substrates may be due to the much stronger acidity of the sulphate group of
      L-serine-O-sulphate compared to carboxyl groups of L-glutamate or D-aspartate. 6.
      These results highlight some of the differences in the way different glutamate
      transporter subtypes transport substrates. This may be used to understand further
      the transport process and develop subtype selective inhibitors of glutamate
      transport.

PMID- 9605567
TI  - The effects of nifedipine and other calcium antagonists on the glibenclamide
      sensitive K+ currents in smooth muscle cells from pig urethra.
AB  - 1. The effects of nifedipine on both levcromakalim-induced membrane currents and
      unitary currents in pig proximal urethra were investigated by use of patch-clamp
      techniques (conventional whole-cell configuration and cell-attached patches). 2.
      Nifedipine had a voltage-dependent inhibitory effect on voltage-dependent Ba2+
      currents at - 50 mV (Ki=30.6 nM). 3. In current-clamp mode, subsequent
      application of higher concentrations of nifedipine (> or =30 microM) caused a
      significant depolarization even after the membrane potential had been
      hyperpolarized to approximately -82 mV by application of 100 microM
      levcromakalim. 4. The 100 microM levcromakalim-induced inward current
      (symmetrical 140 mM K+ conditions, -50 mV) was inhibited by additional
      application of three different types of Ca antagonists (nifedipine, verapamil and
      diltiazem, all at 100 microM). In contrast, Bay K 8644 (1 microM) possessed no
      activating effect on the amplitude of this glibenclamide-sensitive current. 5.
      When 100 microM nifedipine was included in the pipette solution during
      conventional whole-cell recording at -50 mV, application of levcromakalim (100
      microM) caused a significant inward membrane current which was suppressed by 5
      microM glibenclamide. On the other hand, inclusion of 5 microM glibenclamide in
      the pipette solution prevented levcromakalim from inducing an inward membrane
      current. 6. The levcromakalim-induced K+ channel openings in cell-attached
      configuration were suppressed by subsequent application of 5 microM glibenclamide
      but not of 100 microM nifedipine. 7. These results suggest that in pig proximal
      urethra, nifedipine inhibits the glibenclamide-sensitive 43 pS K+ channel
      activity mainly through extracellular blocking actions on the K+ channel itself.

PMID- 9605568
TI  - Contribution of K+ channels and ouabain-sensitive mechanisms to the endothelium
      dependent relaxations of horse penile small arteries.
AB  - 1. Penile small arteries (effective internal lumen diameter of 300 600 microm)
      were isolated from the horse corpus cavernosum and mounted in microvascular
      myographs in order to investigate the mechanisms underlying the endothelium
      dependent relaxations to acetylcholine (ACh) and bradykinin (BK). 2. In arteries
      preconstricted with the thromboxane analogue U46619 (3-30 nM), ACh and BK
      elicited concentration-dependent relaxations, pD2 and maximal responses being
      7.71+/-0.09 and 91+/-1 % (n=23), and 8.80+/-0.07 and 89+/-2% (n=24) for ACh and
      BK, respectively. These relaxations were abolished by mechanical endothelial cell
      removal, attenuated by the nitric oxide (NO) synthase (NOS) inhibitor, NG-nitro-L
      arginine (L-NOARG, 100 microM) and unchanged by indomethacin (3 microM). However,
      raising extracellular K+ to concentrations of 20-30 mM significantly inhibited
      the ACh and BK relaxant responses to 63+/-4% (P<0.01, n=7) and to 59+/-4%
      (P<0.01, n=6), respectively. ACh- and BK-elicited relaxations were abolished in
      arteries preconstricted with K+ in the presence of 100 microM L-NOARG. 3. In
      contrast to the inhibitor of ATP-sensitive K channels, the blockers of Ca2+
      activated K+ (K(Ca)) channels, charybdotoxin (30 nM) and apamin (0.3 microM),
      each induced slight but significant rightward shifts of the relaxations to ACh
      and BK without affecting the maximal responses. Combination of charybdotoxin and
      apamin did not cause further inhibition of the relaxations compared to either
      toxin alone. In the presence of L-NOARG (100 microM), combined application of the
      two toxins resulted in the most effective inhibition of the relaxations to both
      ACh and BK. Thus, pD2 and maximal responses for ACh and BK were 7.65+/-0.08 and
      98+/-1%, and 9.17+/-0.09 and 100+/-0%, respectively, in controls, and 5.87+/-0.09
      (P<0.05, n=6) and 38+/-11% (P<0.05, n=6), and 8.09+/-0.14 (P<0.01, n=6) and 98+/
      1% (n=6), respectively, after combined application of charybdotoxin plus apamin
      and L-NOARG. 4. The selective inhibitor of guanylate cyclase, 1H
      [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 5 microM) did not alter the
      maximal responses to either ACh or BK, but slightly decreased the sensitivity to
      both agonists, deltapD2 being 0.25+/-0.07 (P<0.05, n=6) and 0.62+/-0.12 (P< 0.01,
      n=6) for ACh and BK, respectively. Combined application of ODQ and charybdotoxin
      plus apamin produced further inhibition of the sensitivity to both ACh
      (deltapD2=1.39+/-0.09, P<0.01, n=6) and BK (1.29+/-0.11, P<0.01, n=6), compared
      to either ODQ or charybdotoxin plus apamin alone. 5. Exogenous nitric oxide (NO)
      present in acidified solutions of sodium nitrite (NaNO2) and S-nitrosocysteine
      (SNC) both concentration-dependently relaxed penile resistance arteries, pD2 and
      maximal responses being 4.84+/-0.06 and 82+/-3% (n=12), and 6.72+/-0.07 and 85+/
      4% (n=19), respectively. Charybdotoxin displaced to the right the dose-relaxation
      curves for both NO (deltapD2 0.38+/-0.06, P<0.01, n=6) and SNC (deltapD2 0.50+/
      0.10, P<0.01, n=5), whereas apamin only reduced sensitivity (deltapD2=0.35+/
      0.12, P<0.05, n=5) and maximum response (65+/-9%, P<0.05, n=6) to SNC. ODQ
      shifted to the right the dose-relaxation curves to both NO and SNC. The relaxant
      responses to either NO or SNC were not further inhibited by a combination of ODQ
      and charybdotoxin or ODQ and charybdotoxin plus apamin, respectively, compared to
      either blocker alone. 6. In the presence of 3 microM phentolamine, 5 microM
      ouabain contracted penile resistance arteries by 50+/-6% (n=17) of K-PSS, but did
      not significantly change the relaxant responses to either ACh, BK or NO. However,
      in the presence of L-NOARG ouabain reduced the ACh- and BK-elicited relaxation
      from 94+/-3% to 16+/-5% (P<0.0001, n=6), and from 98+/-2% to 13+/-3% (P<0.0001,
      n=5), respectively. Combined application of ODQ and ouabain inhibited the
      relaxations to NO from 92+/-2% to 26+/-3% (P<0.0001, n=6). 7. The present results
      demonstrate that the endothelium-dependent relaxations of penile small arteries
      involve the release of NO and a non-NO non-prostanoid factor(s) which probably
      hyperpolarize(s) smooth muscle by two different mechanisms: an increased
      charybdotoxin and apamin-sensitive K+ conductance and an activation of the Na+
      K+ATPase. These two mechanisms appear to be independent of guanylate cyclase
      stimulation, although NO itself can also activate charybdotoxin-sensitive K+
      channels and the Na+-K+ pump through both cyclic GMP-dependent and independent
      mechanisms, respectively.

PMID- 9605569
TI  - Endothelin receptors mediating contraction of rat and human pulmonary resistance
      arteries: effect of chronic hypoxia in the rat.
AB  - 1. We examined the endothelin (ET) receptors mediating contractions to ET-1, ET-3
      and sarafotoxin S6c (SX6c) in rat pulmonary resistance arteries by use of peptide
      and non-peptide ET receptor antagonists. Changes induced by pulmonary
      hypertension were examined in the chronically hypoxic rat. The effect of the
      mixed ET(A)/ET(B) receptor antagonist SB 209670 on endothelin-mediated
      contraction was also examined in human pulmonary resistance arteries. 2. In rat
      vessels, the order of potency for the endothelin agonists was SX6c = ET-3 > ET-1
      (pEC50 values in control rats: 9.12+/-0.10, 8.76+/-0.14 and 8.12+/-0.04,
      respectively). Maximum contractions induced by ET-3 and ET-1 were increased in
      vessels from chronically hypoxic rats. 3. The ET(A) receptor antagonist FR 139317
      (1 microM) had no effect on the potency of ET-1 in any vessel studied but
      abolished the increased response to ET-1 in the chronically hypoxic vessels. The
      ET(A) receptor antagonist BMS 182874 (1 microM) increased the potency of ET-1 in
      control rat vessels without effecting potency in the pulmonary hypertensive rat
      vessels. 4. Bosentan (non-peptide mixed ET(A)/ET(B) receptor antagonist)
      increased the potency of ET-1 in control rat vessels but was without effect in
      the pulmonary hypertensive rat vessels. Bosentan (1 microM) inhibited responses
      to SX6c in control and chronically hypoxic rat vessels with pKb values of 5.84
      and 6.11, respectively. The ET(B) receptor antagonist BQ-788 (1 microM) did not
      inhibit responses to ET-1 in any vessel tested but did inhibit responses to both
      SX6c and ET-3 (pKb values in control and chronically hypoxic rat vessels
      respectively: SX6c 7.15 and 7.22; ET-3: 6.68 and 6.89). BQ-788 (1 microM) added
      with BMS 182874 (10 microM) did not inhibit responses to ET-1 in control vessels
      but caused a significant inhibition of responses to ET-1 in chronically hypoxic
      preparations. 5. SB 209670 inhibited responses to ET-1 in both control and
      chronically hypoxic vessels with pKb values of 7.36 and 7.39, respectively. SB
      209670 (0.1 and 1 microM) virtually abolished responses to ET-1 in the human
      pulmonary resistance artery. 6. In conclusion, in rat pulmonary resistance
      arteries, vasoconstrictions induced by ET-1, SX6c and ET-3 are mediated
      predominantly by activation of an ET(B)-like receptor. However, lack of effect of
      some antagonists on ET-1 induced vasoconstriction suggests that ET-1 stimulates
      an atypical ET(B) receptor. The increase in potency of ET-1 in the presence of
      some antagonists suggests the presence of an inhibitory ET(A)-like receptor. The
      influence of this is reduced, or absent, in the chronically hypoxic rats.
      Increased responses to ET-1 are observed in the chronically hypoxic rat and may
      be mediated by increased activation of ET(A) receptors. SB 209670 is unique in
      its potency against responses to ET-1 in both control and chronically hypoxic
      rats, as well as human, isolated pulmonary resistance arteries.

PMID- 9605570
TI  - Neuroregulation of mucus secretion by opioid receptors and K(ATP) and BK(Ca)
      channels in ferret trachea in vitro.
AB  - 1. Opioid agonists inhibit neurogenic mucus secretion in the airways. The
      mechanism of the inhibition is unknown but may be via opening of potassium (K+)
      channels. We studied the effect on neurogenic secretion in ferret trachea in
      vitro of the OP1 receptor (formerly known as delta opioid receptor) agonist [D
      Pen2,5]enkephalin (DPDPE), the OP2 receptor (formely kappa) agonist U-50,488H,
      the OP3 receptor (formerly micro) agonist [D-Ala2, N-Me-Phe, Gly-ol5]enkephalin
      (DAMGO), the ATP-sensitive K+ (K(ATP)) channel inhibitor glibenclamide, the large
      conductance calcium activated K+ (BK(Ca)) channel blocker iberiotoxin, the small
      conductance K(Ca) (SK(Ca)) channel blocker apamin, the K(ATP) channel opener
      levcromakalim, a putative K(ATP) channel opener RS 91309, and the BK(Ca) channel
      opener NS 1619. Secretion was quantified by use of 35SO4 as a mucus marker. 2.
      Electrical stimulation increased tracheal secretion by up to 40 fold above sham
      stimulated levels. DAMGO or DPDPE (10 microm each) significantly inhibited
      neurogenic secretion by 85% and 77%, respectively, effects which were reversed by
      naloxone. U-50,488H had no significant inhibitory effect on neurogenic secretion,
      and none of the opioids had any effect on ACh-induced or [Sar9]substance P
      induced secretion. 3. Inhibition of neurogenic secretion by DAMGO or DPDPE was
      reversed by iberiotoxin (3 microM) but not by either glibenclamide or apamin (0.1
      microM each). Iberiotoxin alone did not affect the neurogenic secretory response.
      4. Levcromakalim, RS 91309 or NS 1619 (3 nM-3 microM) inhibited neurogenic
      secretion with maximal inhibitions at 3 microM of 68%, 72% and 96%, respectively.
      Neither levcromakalim nor RS 91309 at any concentration tested significantly
      inhibited acetylcholine (ACh)-induced secretion, whereas inhibition (60%) was
      achieved at the highest concentration of NS 1619, a response which was blocked by
      iberiotoxin. 5. Inhibition of neurogenic secretion by levcromakalim (3 microM) or
      RS 91309 (30 nM) was inhibited by glibenclamide but not by iberiotoxin. In
      contrast, inhibition by NS 1619 (30 nM and 3 microM) was blocked by iberiotoxin
      but not by glibenclamide. 6. We conclude that, in ferret trachea in vitro, OP1 or
      OP3 opioid receptors inhibit neurogenic mucus secretion at a prejunctional site
      and that the mechanism of the inhibition is via opening of BK(Ca) channels.
      Direct opening of BK(Ca) channels or K(ATP) channels also inhibits neurogenic
      mucus secretion. In addition, opening of BK(Ca) channels inhibits ACh-evoked
      secretion of mucus. Drugs which open BK(Ca) channels may have therapeutic anti
      secretory activity in bronchial diseases in which neurogenic mechanisms and mucus
      hypersecretion are implicated in pathophysiology, for example asthma and chronic
      bronchitis.

PMID- 9605571
TI  - Pharmacological characterization of muscarinic receptors in the uterus of
      oestrogen-primed and pregnant rats.
AB  - 1. Radioligand binding and contractility studies were undertaken to determine the
      subtype/s of muscarinic receptors present in uteri of oestrogen-treated and late
      pregnant rats. 2. Competition binding studies with uterine membrane preparations
      and [3H]-QNB (quinuclidinyl benzilate) provided negative log dissociation
      constants (pKi) for each antagonist as follows; oestrogen-treated - atropine
      (7.98) > or = himbacine (7.83) > methoctramine (7.52) > or =
      hexahydrosiladiphenidol (HHSiD; 7.32) > or = 5,11-dihydro- 11-[[[2-[2 -
      [(dipropylamino)methyl] - 1 piperidinyl]ethyl]amino] - carbonyl] - 6H-pyrido-[2,3
      b][1,4]- benzodiazepin-6-one (AF-DX 384; 7.10)> 11 -[[2- [(diethylamino)methyl]-1
      piperidinyl]-acetyl]5,11-dihydro-6H-pyridol+ ++]2,3,-b][1,4]benzodiazepin-6-one
      (AF-DX 116, 6.77)>pirenzepine (6.17); late pregnant atropine (8.05)> or
      =methoctramine (7.95)> or =himbacine (7.71)> or =HHSiD (7.52)> or =AF-DX 384
      (7.34)>AF-DX 116 (6.72)>pirenzepine (6.18). 3. The potency of carbachol in
      causing uterine contraction was similar in preparations from pregnant and non
      pregnant animals (pD2=5.57 and 5.46, respectively). Each muscarinic antagonist
      caused parallel, rightward shifts of carbachol concentration-response curves. The
      pA2 estimates were: oestrogen-treated - atropine (9.42)> himbacine (8.73) HHSiD
      (8.68) methoctramine (8.49)> or =AF-DX 384 (7.91)> or =AF-DX 116 (7.36)> or
      =pirenzepine (7.26); late pregnant atropine (9.48)>himbacine (8.37)> or = HHSiD
      (8.22) > or =methoctramine (8.01) > or =AF-DX 116 (7.73)> or = AF-DX 384 (7.44)>
      or = pirenzepine (6.92). 4. The relative pKi estimates for antagonists obtained
      in membrane preparations from oestrogen-treated rats suggest the presence of
      muscarinic M2 subtypes. In functional studies pA2 values indicated the additional
      presence of muscarinic M3 receptor or, possibly an atypical receptor subtype. The
      similarity between pKi and pA2 estimates obtained in uteri from oestrogen-treated
      and pregnant animals, respectively, indicates that pregnancy does not affect
      myometrial muscarinic receptors in the rat.

PMID- 9605572
TI  - Effects of adrenomedullin and calcitonin gene-related peptide on contractions of
      the rat aorta and porcine coronary artery.
AB  - 1. Effects of adrenomedullin and alpha-calcitonin gene-related peptide (CGRP) on
      the contractions and cytosolic Ca2+ concentrations ([Ca2+]i) of the rat aorta and
      porcine coronary artery were investigated. Characteristics of the receptors
      mediating the effects of adrenomedullin and alpha-CGRP were also investigated. 2.
      Adrenomedullin and alpha-CGRP caused a concentration-dependent relaxation in the
      rat aorta contracted with noradrenaline. The IC50 values for adrenomedullin and
      alpha-CGRP were 2.4 nM and 4.0 nM, respectively. The relaxant effects of these
      peptides were abolished by removal of the endothelium and significantly
      attenuated by an inhibitor of nitric oxide synthase, NG-monomethyl-L-arginine (L
      NMMA, 100 microM), but not by a cyclo-oxygenase inhibitor, indomethacin (10
      microM). 3. Adrenomedullin and alpha-CGRP increased the endothelial [Ca2+]i in
      the rat aorta with endothelium, whereas they did not change [Ca2+]i in the smooth
      muscle. 4. An antagonist of the CGRP1 receptor, CGRP (8-37), antagonized the
      relaxant effects of alpha-CGRP and the beta-isoform of CGRP (beta-CGRP) but not
      those of adrenomedullin in the rat aorta. 5. In the porcine coronary artery
      contracted with U46619, adrenomedullin and alpha-CGRP caused a concentration
      dependent relaxation with an IC50 of 27.6 and 4.1 nM, respectively. Removal of
      the endothelium altered neither the IC50 values nor the maximal relaxations
      induced by adrenomedullin or alpha-CGRP. When the artery was contracted with high
      K+ solution (72.7 mM), these peptides caused a small relaxation. 6.
      Adrenomedullin and alpha-CGRP increased cyclic AMP content and decreased the
      smooth muscle [Ca2+]i in the porcine coronary artery. 7. CGRP (8-37)
      significantly antagonized the relaxant effects of adrenomedullin and alpha-CGRP
      in the porcine coronary artery. However, it had little effect on the relaxations
      induced by the beta-isoform of CGRP (beta-CGRP). 8. These results suggest that in
      the rat aorta, adrenomedullin and alpha-CGRP increase the endothelial [Ca2+]i,
      activate nitric oxide synthase and release nitric oxide, without a direct
      inhibitory action on smooth muscle. In the porcine coronary artery, in contrast,
      adrenomedullin and alpha-CGRP directly act on smooth muscle, increase cyclic AMP
      content, decrease the smooth muscle [Ca2+]i and inhibit contraction. The rat
      aortic endothelium seems to express the CGRP receptor which is sensitive to alpha
      CGRP, beta-CGRP and CGRP (8-37) and the adrenomedullin specific receptor. The
      porcine coronary smooth muscle, in contrast, seems to express two types of CGRP
      receptor; one of which is sensitive to alpha-CGRP, CGRP (8-37) and adrenomedullin
      and the other is sensitive only to beta-CGRP.

PMID- 9605573
TI  - Agonistic properties of alniditan, sumatriptan and dihydroergotamine on human 5
      HT1B and 5-HT1D receptors expressed in various mammalian cell lines.
AB  - 1. Alniditan, a novel migraine abortive agent, is a potent 5-HT1B/5-HT1D receptor
      agonist of nM affinity. We compared the agonistic properties of alniditan,
      sumatriptan and dihydroergotamine on the cloned human 5-HT1B receptor expressed
      at 200 fmol mg(-1) protein (Bmax) in non-induced L929sA cells, at 740 fmol mg(-1)
      protein in HEK 293 and at 2300 fmol mg(-1) protein in mIFNbeta-induced L929sA
      cells, and on the human cloned 5-HT1D receptor expressed in C6 glioma cells (Bmax
      780 fmol mg(-1) protein). 2. Sodium butyrate treatment increased the expression
      level of human (h)5-HT1B receptors in HEK 293 cells and h5-HT1D receptors in C6
      glioma cells approximately 3 fold, the binding affinities of [3H]-5-HT and [3H]
      alniditan were unaffected. 3. Agonistic properties were evaluated based on
      inhibition of cyclic AMP accumulation in the cells after stimulation of adenylyl
      cyclase by forskolin or isoproterenol. Alniditan, sumatriptan and
      dihydroergotamine were full agonists at the hS-HT1B receptor (IC50 values were
      1.7, 20 and 2 nM, respectively in HEK 293 cells) and hS-HT1D receptors (IC50
      values of 1.3, 2.6 and 2.2 nM, respectively). At the h5-HT1B receptor the agonist
      potency of the compounds slightly increased with higher receptor density. The
      opposite was seen for antagonists (ocaperidone, risperidone and ritanserin). 4.
      This comparative study demonstrated that alniditan was 10 times more potent than
      sumatriptan at the h5-HT1B receptor, and twice as potent at the h5-HT1D receptor.
      Dihydroergotamine was more potent an agonist at the h5-HT1B receptor when
      expressed at high and low level in L929sA cells (but not in HEK 293 cells), and
      was less potent at the hS-HT1D receptor.

PMID- 9605574
TI  - Effects of CGS 21680, a selective A2A adenosine receptor agonist, on cardiac
      output and vascular resistance in acute heart failure in the anaesthetized rat.
AB  - 1. The effects of CGS 21680, a selective A2A adenosine receptor agonist, on
      cardiac output, blood pressure, mean circulatory filling pressure (Pmcf),
      arterial and venous resistances, heart rate and left ventricular end-diastolic
      pressure were assessed in rats with acute heart failure by means of coronary
      artery occlusion. 2. Animals (n=6 in each group) were divided into five groups:
      group I, sham-operated vehicle-treated (0.9% saline; 0.018 mL min(-1)); groups II
      V, subject to coronary artery occlusion and treated with vehicle (0.9% saline;
      0.018 ml min(-1)) and CGS 21680 (0.1, 0.3 and 1.0 microg kg(-1) min(-1)),
      respectively. Haemodynamic measurements were taken one hour after completion of
      surgery, ninety minutes after coronary artery occlusion (except in group I), and
      fifteen minutes after infusion of saline or CGS 21680. 3. Baseline haemodynamic
      measurements before occlusion were found not to differ significantly between the
      different groups of animals. However, after occlusion, cardiac output, rate of
      rise in left ventricular pressure (+ dP/dt) and blood pressure were significantly
      reduced when compared to corresponding values in sham-operated animals. In
      addition, occlusion of the coronary artery resulted in a significant elevation in
      venous resistance, Pmcf and left ventricular end-diastolic pressure as compared
      to corresponding values in sham-operated animals. 4. Infusion with CGS 21680 at
      the highest dose significantly reduced blood pressure, arterial resistance and
      left ventricular end-diastolic pressure when compared to occluded vehicle-treated
      animals (group II). Administration of CGS 21680 at the highest dose also
      significantly increased cardiac output (28%) and heart rate (10%) in comparison
      to occluded vehicle-treated animals. In addition, the highest dose of CGS 21680
      significantly reduced Pmcf (9%) and venous resistance (62%) in comparison to
      occluded vehicle-treated animals. Administration of CGS 21680 did not
      significantly affect +dP/dt when compared to occluded vehicle-treated animals. 5.
      The results from the present investigation indicate that occlusion of the
      coronary artery in rats results in a state of heart failure characterized by
      reduced arterial pressure and cardiac output, and increased venous resistance,
      Pmcf and left ventricular end-diastolic pressure. Administration of CGS 21680 to
      animals with acute heart failure resulted in increased cardiac output which was
      due to reduced venous resistance, as well as increased heart rate.

PMID- 9605575
TI  - Pharmacological characterization of CGRP receptors mediating relaxation of the
      rat pulmonary artery and inhibition of twitch responses of the rat vas deferens.
AB  - 1. CGRP receptors mediating vasorelaxation of the rat isolated pulmonary artery
      and inhibition of contractions of the rat isolated prostatic vas deferens were
      investigated using CGRP agonists, homologues and the antagonist CGRP8-37. 2. In
      the pulmonary artery, human (h)alpha-CGRP-induced relaxation of phenylephrine
      evoked tone was abolished either by removal of the endothelium or by NG-nitro-L
      arginine (10(-5) M). The inhibitory effect of NG-nitro-L-arginine was
      stereoselectively reversed by L- but not by D-arginine (10(-4) M). Thus, CGRP
      acts via nitric oxide released from the endothelium. 3. In the endothelium-intact
      artery, halpha-CGRP, hbeta-CGRP and human adrenomedullin (10(-10) - 3 x 10(-7)
      M), dose-dependently relaxed the phenylephrine-induced tone with similar potency.
      Compared with halpha-CGRP, rat amylin was around 50 fold less potent, while
      [Cys(ACM2,7)] halpha-CGRP (10(-7) - 10(-4) M) was at least 3000 fold less potent.
      Salmon calcitonin was inactive (up to 10(-4) M). 4 Human alpha-CGRP8-37 (3 x 10(
      7) - 3 x 10(-6) M) antagonized halpha-CGRP (pA2 6.9, Schild plot slope 1.2+/-0.1)
      and hbeta-CGRP (apparent pKB of 7.1+/-0.1 for halpha-CGRP8-37 10(-6) M) in the
      pulmonary artery. Human beta-CGRP8-37 (10(-6) M) antagonized halpha-CGRP
      responses with a similar affinity (apparent pKB 7.1+/-0.1). Human adrenomedullin
      responses were not inhibited by halpha-CGRP8-37 (10(-6) M). 5. In the prostatic
      vas deferens, halpha-CGRP, hbeta-CGRP and rat beta-CGRP (10(-10) - 3 x 10(-7) M)
      concentration-dependently inhibited twitch responses with about equal potency,
      while rat amylin (10(-8) - 10(-5) M) was around 10 fold less potent and the
      linear analogue [Cys(ACM2,7)] halpha-CGRP was at least 3000 fold weaker. Salmon
      calcitonin was inactive (up to 10(-4) M). 6 The antagonist effect of halpha-CGRP8
      37 (10(-5) 3 x 10(-5)) in the vas deferens was independent of the agonist, with
      pA2 values against halpha-CGRP of 6.0 (slope 0.9+/-0.1), against hbeta-CGRP of
      5.8 (slope 1.1+/-0.1), and an apparent pKB value of 5.8+/-0.1 against both rat
      beta-CGRP and rat amylin. Human beta-CGRP8-37 (3 x 10(-5) - 10(-4) M)
      competitively antagonized halpha-CGRP responses (pA2 5.6, slope 1.1+/-0.2). The
      inhibitory effect of halpha-CGRP on noradrenaline-induced contractions in both
      the prostatic and epididymal vas deferens was antagonized by halpha-CGRP8-37 (pA2
      5.8 and 5.8, slope 1.0+/-0.2 and 1.0+/-0.3, respectively). 7 The effects of
      halpha-CGRP and halpha-CGRP8-37 in both rat pulmonary artery and vas deferens
      were not significantly altered by pretreatment with peptidase inhibitors
      (amastatin, bestatin, captopril, phosphoramidon and thiorphan, all at 10(-6) M).
      The weak agonist activity of [Cys(ACM2,7)] halpha-CGRP in the vas deferens was
      not increased by peptidase inhibitors. 8 These data demonstrate that two
      different CGRP receptors may exist in the rat pulmonary artery and vas deferens,
      a CGRP1 receptor subtype in the rat pulmonary artery (CGRP8-37 pA2 6.9), while
      the lower affinity for CGRP8-37 (pA2 6.0) in the vas deferens is consistent with
      a CGRP2 receptor.

PMID- 9605576
TI  - Involvement of calcitonin gene-related peptide (CGRP) receptors in insulin
      induced vasodilatation in mesenteric resistance blood vessels of rats.
AB  - 1. The vascular effect of insulin in the mesenteric resistance blood vessel and
      the role of calcitonin generelated peptide (CGRP)-receptor in insulin-induced
      vascular responsiveness were investigated in rats. 2. The mesenteric vascular
      beds isolated from Wistar rats were perfused with Krebs solution, and perfusion
      pressure was measured with a pressure transducer. In preparations contracted by
      perfusion with Krebs solution containing methoxamine in the presence of
      guanethidine, the perfusion of insulin (from 0.1 to 3000 nM) caused a
      concentration-dependent decrease in perfusion pressure due to vasodilatation. The
      pD2 value and maximum relaxation (%) were 6.94+/-0.22 and 43.9+/-5.2,
      respectively. 3. This vasodilator response to insulin was unaffected by 100 nM
      propranolol (beta-adrenoceptor antagonist) plus 100 nM atropine (muscarinic
      cholinoceptor antagonist), 100 microM L-NG-nitroarginine (nitric oxide synthase
      inhibitor), 1 microM ouabain (Na+-K+ ATPase inhibitor), or 1 microM glibenclamide
      (ATP sensitive K+-channel inhibitor). 4. In preparations without endothelium,
      perfusion of insulin produced a marked vasodilatation. The pD2 value and maximum
      relaxation (%) were 7.62+/-0.21 and 81.0+/-4.6, respectively, significantly
      greater than in preparations with intact endothelium. 5. The vasodilator
      responses to insulin in the preparations without endothelium were significantly
      inhibited by CGRP[8 37], a CGRP receptor antagonist, whereas pretreatment with
      capsaisin, a toxin for CGRP-containing nerves, did not affect insulin-induced
      vasodilatation. 6. These results suggest that insulin induces non-adrenergic, non
      cholinergic and endothelium-independent vasodilatation, which is partially
      mediated by CGRP receptors.

PMID- 9605577
TI  - Effect of trans-resveratrol, a natural polyphenolic compound, on human
      polymorphonuclear leukocyte function.
AB  - 1. Polymorphonuclear leukocytes (PMN) may contribute to the pathogenesis of acute
      coronary heart disease (CHD). 2. Epidemiological and laboratory evidence suggests
      that red wine, by virtue of its polyphenolic constituents, may be more effective
      than other alcoholic beverages in reducing the risk of CHD mortality. 3 The aim
      of the present study was to investigate the effects of trans-resveratrol (3,4',5
      trihydroxy-trans-stilbene), a polyphenol present in most red wines, on functional
      and biochemical responses of PMN, upon in vitro activation. 4. trans-Resveratrol
      exerted a strong inhibitory effect on reactive oxygen species produced by PMN
      stimulated with 1 microM formyl methionyl leucyl phenylalamine (fMLP) (IC50 1.3+/
      0.13 microM, mean+/-s.e.mean), as evaluated by luminol-amplified
      chemiluminescence. 5. trans-Resveratrol prevented the release of elastase and
      beta-glucuronidase by PMN stimulated with the receptor agonists fMLP (1 microM,
      IC50 18.4+/-1.8 and 31+/-1.8 microM), and C5a (0.1 microM, IC50 41.6+/-3.5 and
      42+/-8.3 microM), and also inhibited elastase and beta-glucuronidase secretion
      (IC50 37.7+/-7 and 25.4+/-2.2 microM) and production of 5-lipoxygenase
      metabolites leukotriene B4 (LTB4), 6-trans-LTB4 and 12-trans-epi-LTB4 (IC50 48+/
      7 microM) by PMN stimulated with the calcium ionophore A23187 (5 microM). 6.
      trans-Resveratrol significantly reduced the expression and activation of the
      beta2 integrin MAC-1 on PMN surface following stimulation, as revealed by FACS
      analysis of the binding of an anti-MAC-1 monoclonal antibody (MoAb) and of the
      CBRM1/5 MoAb, recognizing an activation-dependent epitope on MAC-1. Consistently,
      PMN homotypic aggregation and formation of mixed cell-conjugates between PMN and
      thrombin-stimulated fixed platelets in a dynamic system were also prevented by
      transresveratrol. 7. These results, indicating that trans-resveratrol interferes
      with the release of inflammatory mediators by activated PMN and down-regulates
      adhesion-dependent thrombogenic PMN functions, may provide some biological
      plausibility to the protective effect of red wine consumption against CHD.

PMID- 9605578
TI  - Sex differences in the relative contributions of nitric oxide and EDHF to agonist
      stimulated endothelium-dependent relaxations in the rat isolated mesenteric
      arterial bed.
AB  - 1. We have used the isolated, buffer-perfused, superior mesenteric arterial bed
      of male and female rats to assess the relative contributions of nitric oxide (NO)
      and the endothelium-derived hyperpolarizing factor (EDHF) to endothelium
      dependent relaxations to carbachol. 2. Carbachol caused dose-related relaxations
      of methoxamine-induced tone in mesenteric vascular beds from male rats described
      by an ED50(M) of 0.43+/-0.15 nmol and a maximum relaxation (Rmax(M) of 89.6+/
      1.2% (n=28) which were not significantly different from those observed in
      mesenteries from female rats (ED50(F)=0.72+/-0.19 nmol and Rax(F)=90.7+/-0.9%;
      n=22). 3. In the males, the addition of 100 microM NG-nitro-L-arginine methyl
      ester (L-NAME) caused the dose-response curve to carbachol to be significantly
      (P<0.001) shifted to the right 15 fold (ED50(M)=6.45+/-3.53 nmol) and
      significantly (P<0.01) reduced Rmax(M) (79.7+/-2.8%, n=13). By contrast, L-NAME
      had no effect on vasorelaxation to carbachol in mesenteries from female rats
      (ED50(f)= 0.89+/-0.19 nmol, Rmax(F)=86.9+/-2.3%, n=9). 4. Raising tone with 60 mM
      KCl significantly reduced the maximum relaxation to carbachol in mesenteries from
      male rats 2 fold (Rmax(M)=40.3+/-9.2%, n=4; P<0.001) and female rats by 1.5 fold
      (Rmax(F)=55.3+/-3.3%, n=6; P<0.001), compared with methoxamine-induced tone. The
      potency of carbachol was also significantly reduced 1.2 fold in preparations from
      males (ED50(M)=0.87+/-0.26 nmol; P<0.01) but not the females (ED50(F)=4.04+/-1.46
      nmol). In the presence of both 60 mM KCl and L-NAME, the vasorelaxation to
      carbachol was completely abolished in mesenteries from both groups. 5. The
      cannabinoid receptor antagonist SR141716A (1 microM), which is also a putative
      EDHF antagonist, had no significant effect on the responses to carbachol in
      mesenteries from males or females (ED50(M)=1.41+/-0.74 nmol, Rmax(M)=89.4+/-2.5%,
      n=7; ED50(F)=2.17+/-0.95 nmol, Rmax(F)=89.9+/-1.8%, n=9). In mesenteries from
      male rats, in the presence of 100 microM L-NAME, SR141716A significantly (P<0.05)
      shifted the dose-response curve to carbachol 8 fold further to the right than
      that seen in the presence of L-NAME alone (ED50(M)= 53.8+/-36.8 nmol) without
      affecting Rmax(M) (72.4+/-4.8%, n=10). In mesenteries from female rats, the
      combined presence of L-NAME and SR141716A, significantly (P < 0.01) shifted the
      dose-response curve to carbachol 7.5 fold, (ED50(F)=6.66+/-2.46 nmol), as
      compared to L-NAME alone and significantly (P<0.001) decreased Rmax(F) (70.1+/
      5.5%, n=8). 6. Vasorelaxations to the nitric oxide donor sodium nitroprusside
      (SNP), to the endogenous cannabinoid, anandamide (a putative EDHF) and to the ATP
      sensitive potassium channel activator, levcromakalim, did not differ
      significantly between male and female mesenteric vascular beds. 7. The continuous
      presence of sodium nitroprusside (SNP; 20-60 nM) had no effect on vasorelaxation
      to carbachol in mesenteries from either males or females. In the presence of L
      NAME, SNP significantly (P<0.05) reduced the potency of carbachol 6 fold, without
      affecting the maximal relaxation in mesenteries from male rats (ED50(M)=40.9+/
      19.6 nmol, Rmax(M)=79.4+/-2.5%, n=11). Similarly in mesenteries from female rats,
      the ED50(F) was also significantly (P<0.01) increased 7 fold (6.24+/-2.02 nmol),
      while the Rmax(F) was unaffected (81.9+/-11.0%; n=4). 8 The results of the
      present investigation demonstrate that the relative contributions of agonist
      stimulated NO and EDHF to endothelium-dependent relaxations in the rat isolated
      mesenteric arterial bed, differ between males and females. Specifically, although
      both NO and EDHF appear to contribute towards endothelium-dependent relaxations
      in males and females, blockade of NO synthesis alone has no effect in the female.
      This suggests that EDHF is functionally more important in females; one possible
      explanation for this is that in the absence of NO, the recently identified
      ability of EDHF to compensate for the loss of NO, is functio

PMID- 9605579
TI  - Effect of chronic m-CPP on locomotion, hypophagia, plasma corticosterone and 5
      HT2C receptor levels in the rat.
AB  - 1. The present study examined 5-HT2C receptor agonist-induced behavioural
      tolerance and 5-HT2C receptor down-regulation in adult rat brain. The effect of
      chronic subcutaneous infusion of the 5-HT2C receptor agonist, m
      chlorophenylpiperazine (m-CPP, 10 mg kg(-1), day(-1)), for 14 days was examined
      on daily food intake, the ability of acute m-CPP (2.5 mg kg(-1), i.p.) to induce
      hypolocomotion in a novel arena and elevate plasma corticosterone levels and on
      ex vivo cortical [3H]-mesulergine binding and hippocampal 5-HT2C receptor protein
      levels. 2. Before chronic infusion, m-CPP (2.5 mg kg(-1), i.p.) attenuated the
      number of turns and rears made in a novel open field arena. In contrast, while m
      CPP still elicited this hypolocomotion following 14 days, saline infusion, no
      such hypolocomotion occurred in rats given chronic m-CPP (10 mg kg(-1) day(-1)),
      indicating that almost complete tachyphylaxis of this behaviour occurred with
      chronic 5-HT2C receptor agonist injection. 3. During chronic infusion of m-CPP,
      rats consumed less food per day than saline-treated controls. Acute challenge
      with m-CPP following two weeks, treatment still attenuated food intake over the
      next four hours (by 43% and 30%, respectively from that on the previous day) in
      saline and m-CPP infusion groups, showing that only partial tolerance to 5-HT2C
      receptor agonist-induced hypophagia occurred. 4. In naive home cage rats, plasma
      corticosterone was elevated in a dose-dependent manner 35 min after m-CPP
      injection (0.5, 1 and 3 mg kg(-1), i.p.) but levels were comparable to control
      values 16 h after m-CPP (2, 5 and 10 mg kg(-1), i.p.). Sixteen hours after a
      single m-CPP injection (2.5 mg kg(-1), i.p.), plasma corticosterone levels were
      comparable in a group of rats which had received 14 days infusion of m-CPP or
      saline. However, following a similar acute m-CPP injection (2.5 mg kg(-1), i.p., 
      16 h) in rats previously infused for 14 days with m-CPP, plasma corticosterone
      levels were lower than those in a separate group which received no chronic
      infusions (but only acute m-CPP injection), even though the plasma m-CPP levels
      were comparable in both groups. The data are consistent with the proposal that
      chronic m-CPP induced some down-regulation of hypothalamic 5-HT2C receptors which
      contribute, in a tonic manner, to plasma corticosterone secretion under the
      conditions investigated. 5. Chronic m-CPP infusion reduced the amount of [3H]
      mesulergine binding (by 27%, without altering the KD) in membranes prepared from
      parietal/occipital/temporal cortex (under conditions to exclude binding to 5-HT2A
      receptors) and 5-HT2C receptor protein-like immunoreactive levels measured by
      radioimmunoassay in the hippocampus by 38%, confirming that 5-HT2C receptor down
      regulation had occurred. 6. Even after 14 days m-CPP infusion only partial
      behavioural tolerance and 5-HT2C receptor down-regulation were observed, which
      may vary in different brain regions of the rat. Thus the hypophagia produced by m
      CPP may involve activation of 5-HT2C receptors in the hypothalamus, where there
      is a greater receptor reserve or which are more resistant to agonist-induced down
      regulation than 5-HT2C receptors in limbic areas (striatum and nucleus accumbens)
      mediating m-CPP-induced hypolocomotion.

PMID- 9605580
TI  - Involvement of protein kinases in the induction of NO synthase II in human DLD-1
      cells.
AB  - 1. Protein phosphorylation is involved in the induction of nitric oxide synthase
      II (NOS II, iNOS) in several types of animal cells. Here we have investigated the
      possible involvement of major protein kinases in the induction of NOS II
      expression in human DLD-1 cells. 2. In DLD-1 cells, interferon--gamma alone
      induced a submaximal NOS II expression; a cytokine mixture consisting of
      interferon-gamma, tumour necrosis factor-alpha and interleukin-1beta produced
      maximal NOS II induction. 3. Activators of protein kinase A (forskolin, 8
      dibutyryl-cyclic AMP), of protein kinase C (tetradecanoylphorbol-13-acetate), and
      of protein kinase G (8-bromo cyclic GMP) did not induce NOS II mRNA by
      themselves, nor did they alter NOS II mRNA induction in response to cytokines. 4.
      Inhibitors of protein kinase A (compound H89), of protein kinase C
      (bisindolylmaleimide, chelerythrine or staurosporine), of phosphatidylinositol 3
      kinase (wortmannin), of p38 mitogen-activated protein kinase (compound SB 203580)
      and of extracellular signal-regulated kinase (compound PD 98059) also had no
      influence on basal or cytokine-induced NOS II mRNA expression. 5.
      Immunoprecipitation kinase assays showed no activation of extracellular signal
      regulated kinase or p38 mitogen-activated protein kinase in cytokine-incubated
      DLD-1 cells. The c-Jun NH2-terminal kinase was activated by cytokines, but the
      most efficacious cytokine was tumour necrosis factor-alpha which did not induce
      NOS II by itself. 6. In contrast, the protein tyrosine kinase inhibitor
      tyrphostin B42 (a specific inhibitor of interferon-gamma-activated janus kinase
      2) and the protein tyrosine kinase inhibitor tyrphostin A25 both reduced CM
      induced NOS II mRNA expression in a concentration-dependent manner. 7. These
      results suggest that activation of NOS II expression in DLD-1 cells is
      independent of the activities of protein kinases A, C and G, phosphatidylinositol
      3-kinase, extracellular signal regulated kinase and p38 mitogen-activated protein
      kinase, but seems to require protein tyrosine kinase activity, especially the
      interferon-gamma-activated janus kinase 2.

PMID- 9605581
TI  - [3H]-SCH 58261 labelling of functional A2A adenosine receptors in human
      neutrophil membranes.
AB  - 1. The present study describes the direct labelling of A2A adenosine receptors in
      human neutrophil membranes with the potent and selective antagonist radioligand,
      [3H]-5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4 triazolo[l,5
      c]pyrimidine, ([3H]-SCH 58261). In addition, both receptor affinity and potency
      of a number of adenosine receptor agonists and antagonists were determined in
      binding, adenylyl cyclase and superoxide anion production assays. 2. Saturation
      experiments revealed a single class of binding sites with Kd and Bmax values of
      1.34 nM and 75 fmol mg(-1) protein, respectively. Adenosine receptor ligands
      competed for the binding of 1 nM [3H]-SCH 58261 to human neutrophil membranes,
      with a rank order of potency consistent with that typically found for
      interactions with the A2A adenosine receptors. In the adenylyl cyclase and in the
      superoxide anion production assays the same compounds exhibited a rank order of
      potency identical to that observed in binding experiments. 3. Thermodynamic data
      indicated that [3H]-SCH 58261 binding to human neutrophils is entropy and
      enthalpy-driven. This finding is in agreement with the thermodynamic behaviour of
      antagonists binding to rat striatal A2A adenosine receptors. 4. It was concluded
      that in human neutrophil membranes, [3H]-SCH 58261 directly labels binding sites
      with pharmacological properties similar to those of A2A adenosine receptors of
      other tissues. The receptors labelled by [3H]-SCH 58261 mediated the effects of
      adenosine and adenosine receptor agonists to stimulate cyclic AMP accumulation
      and inhibition of superoxide anion production in human neutrophils.

PMID- 9605582
TI  - Dependence of P2-nucleotide receptor agonist-mediated endothelium-independent
      relaxation on ectonucleotidase activity and A2A-receptors in rat portal vein.
AB  - 1. The mechanism of action of P2 nucleotide receptor agonists that produce
      endothelium-independent relaxation and the influence of ecto-ATPase activity on
      this relaxing effect have been investigated in rat portal vein smooth muscle. 2.
      At 25 degrees C, ATP, 2-methylthioATP (2-MeSATP) and 2-chloroATP (2-ClATP), dose
      dependently inhibited spontaneous contractile activity of endothelium-denuded
      muscular strips from rat portal vein. The rank order of agonist potency defined
      from the half-inhibitory concentrations was 2-CIATP (2.7+/-0.5 microM, n=7) >ATP
      (12.9+/-1.1 microM, n=9) > or =2-MeSATP (21.9+/-4.8 M, n=4). In the presence of
      alphabeta-methylene ATP (alphabeta-MeATP, 200 microM) which itself produced a
      transient contractile effect, the relaxing action of ATP and 2-MeSATP was
      completely abolished and that of 2-ClATP strongly inhibited. 3. The non-selective
      P2-receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid
      (PPADS, 100 microM) did not affect the relaxation induced by ATP, 2-MeSATP, and 2
      ClATP. 4. The A2A-adenosine receptor antagonist ZM 241385 inhibited the ATP
      induced relaxation in a concentration-dependent manner (1-100 nM). In the
      presence of 100 nM ZM 241385, the relaxing effects of 2-MeSATP and 2-ClATP were
      also inhibited. 5. ADP, AMP and adenosine also produced concentration-dependent
      inhibition of spontaneous contractions. The relaxing effects of AMP and adenosine
      were insensitive to alphabeta-MeATP (200 microM) but were inhibited by ZM 241385
      (100 nM). 6. Simultaneous measurements of contraction and ecto-ATPase activity
      estimated by the degradation of [gamma-32P]-ATP showed that muscular strips
      rapidly (10-60 s) hydrolyzed ATP. This ecto-ATPase activity was abolished in the
      presence of EDTA and was inhibited by 57+/-11% (n=3) by 200 microM alphabeta
      MeATP. 7. These results suggest that ATP and other P2-receptor agonists are
      relaxant in rat portal vein smooth muscle, because ectonucleotidase activity
      leads to the formation of adenosine which activates A2A-receptors.

PMID- 9605583
TI  - Craniometaphyseal dysplasia in six generations of a German kindred.
AB  - Craniometaphyseal dysplasia (CMD) was found in 6 generations of a large German
      kindred; 24 affected individuals were identified. The clinical diagnosis was
      confirmed by further examinations in 15 individuals, including 2 exhumed
      skeletons. Five deceased individuals were considered to be undoubtedly affected
      by reviewing photographs, and 4 must have had CMD from genealogical
      considerations. Pedigree analysis was performed over 8 generations back to
      persons born at the beginning of the 18th century in a central area of Germany.
      The trait could be traced back to a common male ancestor, born in 1790. Molecular
      genetic investigations on 3 generations of this kindred are in progress. In the
      present study we describe the clinical characteristics of the family.

PMID- 9605584
TI  - Bilateral radial ray hypoplasia with multiple epiphyseal dysplasia.
AB  - We describe a 5-4/12-year-old girl with the unique combination of bilateral
      radial ray hypoplasia and multiple epiphyseal dysplasia (MED). Radial ray
      hypoplasia was diagnosed at birth. MED was documented at age 4-3/12 years when
      she presented with leg pain and short stature and was found to have femoral
      anteversion and tibial torsion giving rise to severe genu valgum deformity and
      intoeing. She has no facial anomalies and is developmentally normal. Family
      history is unremarkable and chromosomal analysis was normal. Investigation of
      mineral metabolism showed idiopathic hypercalciuria. Surgical lengthening of her
      severely hypoplastic left radius at age 19 months was successful. Bilateral
      femoral and tibial osteotomies at age 5-4/12 years corrected her lower limb
      deformities. This combination of two distinctive but rare skeletal abnormalities
      may represent a new syndrome.

PMID- 9605585
TI  - Prenatal diagnosis of a constitutional interstitial deletion of chromosome 5
      (q15q31.1) presenting with features of congenital contractural arachnodactyly.
AB  - Prenatal diagnosis of a constitutional interstitial deletion of chromosome 5
      (q15q31.1) in a 30-year-old woman is reported. At 21 weeks of pregnancy, routine
      fetal ultrasounds showed the presence of apparently isolated bilateral club feet.
      Fetal karyotyping documented an interstitial deletion of the long arm of
      chromosome 5: 46,XX,del(5) (q15q31) in all 50 analyzed metaphases. Because such
      deletion is associated with severe psychomotor retardation, the pregnancy was
      terminated. Postmortem karyotyping of skin fibroblasts confirmed the presence of
      this interstitial de novo deletion in all mitoses. The breakpoints on 5q were
      analyzed by fluorescent in situ hybridization and were localized at 5q15 and
      q31.1. This case illustrates the importance of fetal karyotyping in cases of
      isolated club feet. At autopsy, the fetus presented had minor anomalies and
      contractures of knee and hip joints. These clinical findings could fit the
      diagnosis of congenital contractural arachnodactyly (CCA) or Beals syndrome. CCA
      is caused by a defect in the fibrillin-2 (FBN2) gene. This gene was previously
      mapped on 5q23-31. Our molecular studies of both parents and the fetus, using an
      intragenic polymorphic GT repeat, showed that the FBN2 gene was deleted in the
      fetus and that the de novo interstitial deletion occurred on the paternally
      inherited chromosome 5. Thus, CCA may be caused by a loss of function of the FBN2
      gene. Clinical findings in this fetus and those of other described cases with
      interstitial 5q deletions are reviewed, and similarities with CCA are stressed.

PMID- 9605586
TI  - Methylenetetrahydrofolate reductase deficiency in a patient with phenotypic
      findings of Angelman syndrome.
AB  - Deficiency of methylenetetrahydrofolate reductase (MTHFR) is associated with a
      variable phenotype that includes mental retardation, gait abnormalities, and
      seizures. Many of the same clinical findings are also seen in patients with
      Angelman syndrome. We report on a patient with MTHFR deficiency who was initially
      diagnosed as having Angelman syndrome. This case illustrates that MTHFR
      deficiency can mimic the phenotype of Angelman syndrome and that MTHFR deficiency
      should be excluded in patients with manifestations of Angelman syndrome whose
      molecular studies of chromosome 15 are normal.

PMID- 9605587
TI  - Male cases of incontinentia pigmenti: case report and review.
AB  - Male patients with Bloch-Sulzberger incontinentia pigmenti (IP type II) are rare
      and more severely affected than their female counterparts, with a significant
      occurrence of sex chromosome aneuploidy. This document introduces a new male IP
      type II patient and reviews 48 males reported with IP. Twenty-eight of the 49
      patients meet current criteria for diagnosis of IP type II. The phenotype is
      variable and the incidence of documented developmental delay is 25%. Five
      patients had Klinefelter syndrome (47,XXY). Most patients were reported prior to
      1961 when chromosome analysis was not available. Biopsy and laboratory reports
      considered to be "consistent with" the diagnosis of IP were seen in patients
      meeting criteria as well as those who would not currently be given the diagnosis.
      The histologic findings considered diagnostic are varied. This variability may be
      accounted for by differences in stage of disease, biopsy site, histologic
      technique, and reporting style. Conversely, this may indicate that the diagnostic
      weight given to the biopsy should be reconsidered. Eosinophilia was not a
      consistent finding. Overall, differences in reporting, ascertainment, and length
      of follow-up lead to difficulty in interpreting or predicting the natural history
      of males with IP type II. Based on the existing literature, they appear to have a
      higher rate of mental retardation than the general population, but there does not
      appear to be a correlation between severity of physical and mental involvement.
      The presence of sex chromosome aneuploidy documented in the more recent cases
      emphasizes the need for chromosome analysis in any male patient suspected of IP
      type II.

PMID- 9605589
TI  - Vertebral and eye anomalies, cutis aplasia, and short stature (VECS): a new
      syndrome?
AB  - We report on a 6-year-old girl with short stature, facial anomalies, cutis
      aplasia, nasolacrimal duct obstruction, megalocorneae, kyphoscoliosis with
      multiple segmentation defects of the thoracic vertebrae, and 11 pairs of ribs.
      These anomalies together may represent a newly recognized syndrome.

PMID- 9605588
TI  - FGFR2 mutation associated with clinical manifestations consistent with Antley
      Bixler syndrome.
AB  - The Antley-Bixler syndrome (ABS) is a rare syndrome with synostosis of cranial
      sutures and elbow joints as minimal diagnostic criteria. The inheritance has been
      suggested to be autosomal recessive based on two families with sib recurrence
      with both sexes being affected, and two cases born to consanguineous parents. We
      report the first case of ABS associated with an apparent dominant de novo
      mutation in the fibroblast growth factor receptor 2 (FGFR2) gene. The patient was
      found to be heterozygous for a C-->G transversion at nucleotide 1064, which
      predicts a Ser351Cys amino acid substitution in the IgIII domain of FGFR2. Apart
      from the craniosynostosis and elbow ankylosis, our patient also presented with
      severe spinal dysraphism, the first report of such a finding in association with
      ABS. This suggests that FGFR2 is expressed as early as the fourth week of
      embryogenesis when somite formation occurs. We propose that the Antley-Bixler
      syndrome is an autosomal dominant condition with possible gonadal mosaicism.
      Alternatively, there may be two types of ABS: an autosomal dominant form and an
      autosomal recessive form. In light of our findings, FGFR mutations should be
      looked for in other craniosynostosis patients with elbow synostosis.

PMID- 9605590
TI  - Phenotypic variability associated with 14 splice-site mutations in the NF2 gene.
AB  - Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder caused by
      mutations in the NF2 gene. Patients carrying NF2 mutations are predisposed to
      cerebral and spinal tumors with bilateral vestibular schwannomas as the hallmark.
      Using single strand conformation polymorphism and temperature gradient gel
      electrophoresis analysis, we have screened 87 unrelated NF2 patients for
      mutations in the NF2 gene. In this study, we report phenotypes associated with 14
      splice-site mutations carried by 14 propositi and 11 relatives. The mutations
      were distributed in exons 2, 3, 5, 7, 8, 14, and 15. These splice-site mutations
      were associated with various phenotypes, from severe to asymptomatic. Phenotypic
      variation was also observed within families. Mutations downstream from exon 8
      resulted more often in mild phenotypes. No meningiomas were found in any of 13
      affected or mutation bearing individuals from three families with splice-site
      mutations of exons 14 and 15. These data suggest that splice-site alteration is a
      relatively common cause of NF2, and that unlike other mutations the clinical
      outcomes of splice-site mutations in the NF2 gene are variable. These results add
      to the growing body of information on genotype-phenotype correlation in NF2.

PMID- 9605591
TI  - A large family with multiple epiphyseal dysplasia linked to COL9A2 gene.
AB  - We describe a large family, including 54 affected individuals, with multiple
      epiphyseal dysplasia (MED) with involvement of the peripheral joints only. In
      this family, a mutation in the COL9A2 gene was detected. Every affected person
      has involvement of the knee joints. Other involved joints are the elbow, ankle,
      wrist, hand, and feet joints. Involvement of the shoulder or hip joints is never
      seen after adolescence. The height of the affected individuals is short to
      normal; spinal involvement is never seen. The penetrance of the gene is complete.
      However, the expression of the gene is highly variable.

PMID- 9605592
TI  - Craniometadiaphyseal dysplasia, wormian bone type.
AB  - We report on a 4-year-old boy with craniometadiaphyseal dysplasia (CMDD), wormian
      bone type. Component manifestations include a large head with prominent forehead,
      skull changes showing multiple wormian bones, wide long tubular bones without the
      usual metaphyseal flare, wide and short tubular bones without the normal
      diaphyseal constriction, and wide ribs and clavicles. In addition to these
      findings, the propositus, his brother, his father, and a paternal aunt all have
      parietal protuberances, which seem not related to CMDD. Parental consanguineity
      supports the autosomal recessive transmission of the condition.

PMID- 9605593
TI  - Different behavior in the paternally vs. maternally inherited mutated allele in
      Brazilian Machado-Joseph (MJD1) families.

PMID- 9605594
TI  - Measurement of testicular volume.

PMID- 9605595
TI  - Central nervous system anomalies in Seckel syndrome: report of a new family and
      review of the literature.

PMID- 9605596
TI  - Combination of ACE inhibitors and calcium antagonists: a logical approach.
AB  - An increasing body of evidence indicates that impairment of endothelial function
      is crucially involved in the pathogenesis of cardiovascular disease. Injury to
      the endothelium precipitates atherosclerosis by causing smooth-muscle cell
      migration and proliferation, induction of expression of growth factors, and
      impairment of plasma coagulation and endogenous fibrinolysis. Angiotensin
      converting enzyme (ACE) inhibitors and calcium antagonists are widely used in
      patients with cardiovascular disease and have beneficial vascular effects beyond
      blood pressure control alone. Both exhibit a synergistic hemodynamic profile.
      Whereas calcium antagonists dilate large conduit and resistance arteries, ACE
      inhibitors inhibit the renin-angiotensin system (RAS) and reduce sympathetic
      outflow. Certain calcium antagonists, such as verapamil and diltiazem, reduce
      heart rate, whereas dihydropyridines tend to increase it. In the blood vessel
      wall, the local vascular effects of ACE inhibitors and calcium antagonists are
      complementary. ACE inhibitors diminish transformation of angiotensin I (Ang I)
      into angiotensin II (Ang II) and prevent degradation of bradykinin [which
      stimulates nitric oxide (NO) and prostacyclin formation]. Calcium antagonists
      inhibit the effects of Ang I and endothelin-1 (ET-1) at the level of vascular
      smooth muscle by reducing Ca2+ inflow and facilitating the vasodilator effects of
      NO. The resistance circulation is particularly dependent on extracellular Ca2+,
      thereby explaining why nifedipine and verapamil effectively inhibit ET-induced
      vasoconstriction in vitro and in vivo. In hypertension, ACE inhibitors and
      calcium antagonists markedly improve structural changes and increase the
      media/lumen ratio in resistance arteries. Long-term combination therapy with
      verapamil and trandolapril is particularly effective in reversing endothelial
      dysfunction in hypertensive animals. ACE inhibitors substantially reduce
      morbidity and mortality in patients with left ventricular dysfunction after
      myocardial infarction (MI). There is a strong trend indicating benefit with
      verapamil as well, but this is confined to patients with a normal left
      ventricular ejection fraction. Clinical studies have confirmed that calcium
      antagonists exhibit antiatherogenic properties. However, the clinical relevance
      of these findings has recently been disputed because short-acting
      dihydropyridines are reported to increase risk for MI. Because ACE inhibitors and
      calcium antagonists exhibit synergistic hemodynamic, antiproliferative,
      antithrombotic, and antiatherogenic properties, combination therapy provides a
      promising concept in patients with cardiovascular and renal disease.

PMID- 9605597
TI  - How to evaluate the duration of blood pressure control: the trough:peak ratio and
      24-hour monitoring.
AB  - Recently published data provide confirming evidence to support existing
      epidemiologic data showing that treatment-induced changes in 24-h blood pressure
      are more closely correlated with treatment-induced changes in left ventricular
      mass index than corresponding changes in clinic blood pressure. This provides
      definitive support for the aim of achieving blood pressure control based on a
      smooth and consistent antihypertensive effect over a full 24-h period. With the
      plethora of agents now available for once-daily administration in the treatment
      of hypertension, it would be of value to have a validated index that defines
      duration of effect and that discriminates between alternative treatments and
      treatment regimens. The trough:peak ratio of blood pressure response has been
      proposed as such as index and has in part been validated in this role. Evidence
      suggests that many existing agents have suboptimal trough:peak ratios or,
      alternatively, that achieving a high ratio is dependent on utilizing
      inappropriately high doses of drug. Where a drug has a high trough:peak ratio
      that is associated with its intrinsic long duration of action and is independent
      of dose over the therapeutic range, the evidence indicates that the drug may
      offer the additional benefit of sustained blood pressure control after a missed
      dose. Finally, theoretic and experimental evidence supports the concept that
      rational drug combinations will produce enhanced trough:peak ratios compared to
      the individual drug components.

PMID- 9605598
TI  - Therapeutic needs of the elderly patient.
AB  - Since 1967, results from well-controlled long-term studies have provided
      convincing evidence for the benefit of antihypertensive therapy in middle-aged
      patients. However, many physicians have hesitated to apply these findings to
      patients over 60 years of age. Recently, the results of several prospective,
      randomized long-term trials of antihypertensive drug treatment in elderly
      hypertensive patients have been published. An analysis of the results of six
      major trials shows that antihypertensive treatment reduces overall mortality by
      20%, cardiovascular mortality by 34%, the incidence of fatal and nonfatal
      cerebrovascular events by 40%, and the complications of coronary heart disease
      (i.e., fatal and nonfatal myocardial infarction and sudden cardiac death) by 16%.
      In absolute terms, antihypertensive therapy is much more beneficial in elderly
      patients than in middle-aged patients with mild hypertension. These results are
      related to both combined systolic and diastolic and to isolated systolic
      hypertension. There is therefore a clear indication for antihypertensive drug
      treatment of elderly hypertensive patients. Selection of the type of
      antihypertensive therapy in elderly hypertensive patients must consider the high
      frequency of isolated systolic hypertension, the multimorbidity, and the need for
      multiple drug prescription. In these circumstances, the fixed combination of an
      angiotensin-converting enzyme inhibitor and a calcium antagonist offers several
      advantages, associated with a high response rate and good tolerability.

PMID- 9605599
TI  - Benefits of combination therapy in hypertensive patients with associated coronary
      artery disease: a subgroup with specific demands.
AB  - Although prevention of coronary artery disease (CAD) is one of the main goals of
      antihypertensive therapy, when first seen hypertensive patients often have
      associated CAD. These patients need a therapy that can exert an acute anti
      ischemic action, such as ad hoc relief of angina pectoris, and can also reduce
      the incidence of myocardial infarction (MI) or reinfarction. Reduction in blood
      pressure (BP) alone does not appear to be adequate because in hypertensive
      patients CAD is a complex and multifactorial process involving not only
      hemodynamic, neurohormonal, and metabolic factors but also hypertension-induced
      myocardial and vascular structural changes, which appear independently to
      contribute to risk for CAD. In theory, antihypertensive combination therapy, by
      summing the different effects of various drugs, appears to have a greater
      capacity for comprehensive management of hypertensive patients with CAD.
      Simultaneous administration of angiotensin-converting enzyme (ACE) inhibitors and
      calcium-channel blockers appears to be particularly effective. In several
      clinical trials with long-term follow-up, ACE inhibitor therapy has been
      associated with a substantial reduction in the risk for major ischemic events.
      The antiproliferative action of ACE inhibitors on myocardium and the vascular
      wall, their hemodynamic effects, antiatherogenic actions, neurohormonal
      attenuation, and certain genetic issues may account for the ability of this class
      of drugs to reduce the risk for CAD-related events. Although ACE inhibitors can
      be expected to increase coronary blood flow when the renin-angiotensin system is
      activated and to reduce BP, ventricular filling pressure, and sympathetic drive,
      thus far an acute anti-ischemic action of these drugs has not been demonstrated.
      Unlike ACE inhibitors, which usually have class-specific effects, there are
      important differences in the clinical effects of various calcium antagonists. The
      first generation of dihydropyridine calcium-entry blockers has failed to
      demonstrate efficacy in secondary prevention of coronary artery events. However,
      verapamil reduces mortality in patients with normal left ventricular function.
      The antihypertensive efficacy of verapamil, its antiatherogenic action, and its
      ability to reverse left ventricular hypertrophy, to improve diastolic function,
      and to interfere with endothelium-derived contracting factors may also account
      for the improved survival of patients with CAD treated with this drug. Moreover,
      verapamil is also effective in the treatment of all types of angina because it
      reduces myocardial oxygen consumption as a result of its hypotensive effect and
      its ability to reduce heart rate, and it may also improve oxygen delivery to the
      myocardium because of its action on coronary vasodilatation. It is also important
      to consider that ACE inhibitors and calcium antagonists often induce the same
      beneficial effects through different mechanisms, thus allowing a synergistic
      action when the two classes of drugs are administered together.

PMID- 9605600
TI  - Diabetic hypertensive patients: improving their prognosis.
AB  - Diabetes is a devastating disease with multiple adverse effects on the
      vasculature. Moreover, hypertension is a prerequisite for patients with diabetes
      to progress to end-stage renal disease and to develop cardiovascular
      complications. Adequate control of blood glucose and blood pressure are the two
      most important factors that predict a favorable renal outcome. Recent studies
      have also shown that some classes of antihypertensive medications, such as the
      angiotensin-converting enzyme (ACE) inhibitors, may be ideal initial agents to
      control blood pressure in the hypertensive diabetic patient and thus to preserve
      renal function. In addition, nondihydropyridine calcium-channel blockers have
      been shown to retard the decline in renal function in patients with non-insulin
      dependent diabetes mellitus (NIDDM) nephropathy who have lost at least 50% of
      their renal function. Retrospective analyses demonstrate that a reduction in
      blood pressure, especially to levels of <130/85 mg Hg in diabetic patients,
      retards the progression of renal disease. Reduction in arterial pressure to these
      low levels is probably more important than the agents used to achieve this goal.
      Because many of these patients require more than one medication to achieve these
      lower levels of arterial pressure, it is clear that fixed-dose combinations of
      such agents will both improve the likelihood of achieving a given blood pressure
      goal as well as medication compliance.

PMID- 9605601
TI  - Present and future role of combination treatment in hypertension.
AB  - Both in clinical practice and in drug trials, combination treatment of
      hypertension plays a fundamental role. This article reviews the features that
      make combined therapy with two drugs valuable, i.e., additive antihypertensive
      efficacy, different mechanisms of action, and reciprocal side-effect
      minimization. Also examined are the advantages and disadvantages of a fixed
      combination, emphasizing that a major advantage is simplification of the
      treatment schedule. This is clinically relevant because complexity of treatment
      negatively affects patient compliance, which in hypertensive patients is poor,
      leading to poor long-term blood pressure control in the hypertensive fraction of
      the population.

PMID- 9605602
TI  - Modification of endometrial arteries during invasion by cytotrophoblast cells in
      the pregnant macaque.
AB  - Fetal trophoblast cells invade endometrial blood vessels and gain access to
      maternal blood within two days after the onset of blastocyst implantation in
      macaques. Soon thereafter, cytotrophoblast cells migrate well into the lumina of
      arteries and subsequently invade arterial walls. Using electron microscopy and
      light microscopy we investigated the interactions between invasive
      cytotrophoblast cells and the cellular and extracellular components in the walls
      of endometrial arteries. The placentas and adjacent endometrium of 22 macaques
      (GD 17 to term) were examined. Spiral arteries containing migratory cytokeratin
      labeled cytotrophoblast cells were identified at all stages examined. Early
      modification of each artery showed that a plug of intraluminal cytotrophoblast
      cells temporarily filled the arterial lumen in the vicinity of the trophoblastic
      shell. Distal to this plug the group of cells tapered as a continuous mass,
      filling only a portion of the lumen. Endothelial cells were displaced from their
      basal lamina by closely apposed cytotrophoblast cell processes. Soon thereafter
      these processes penetrated the basal lamina and achieved contact with smooth
      muscle cells of the tunica media. As cytotrophoblast cells infiltrated the
      arterial wall they hypertrophied and secreted extracellular matrix, thereby
      differentiating into intramural cytotrophoblast. The patent lumen of the artery
      was reestablished concomitant with the migration of intraluminal cytotrophoblast
      cells through the arterial tunica intima and into the tunica media. The presence
      of clusters of cytotrophoblast cells in the arterial wall results in
      discontinuity of the tunica media and dispersion of the smooth muscle. The
      combined changes result in expanded circumferences of invaded arteries as well as
      diminished ability to contract. In portions of arteries adjacent to the
      trophoblastic shell cytotrophoblast usually occupied the entire perimeter and
      thickness of the artery wall, while in areas distal only a portion of the wall
      was invaded. Despite extensive arterial modification, evidence of cell death
      among the fetal and maternal tissues involved was rare. By later gestation only a
      few intraluminal cytotrophoblast cells were seen. Intramural cells were
      surrounded by a thick layer of matrix, but maintained contact with adjacent cells
      through cytoplasmic processes, some of which formed gap junctions. Maternal
      cellular and connective tissue elements were excluded from the cytotrophoblast
      matrix pads and the cytotrophoblast cells retained attributes of glycoprotein
      producing cells to term. Spiral arteries were modified well into the spongiosum
      layer of the endometrium, and some were modified into the myometrium.

PMID- 9605603
TI  - Platelet-derived growth factor-receptor-beta in pig and cattle blastocysts.
AB  - Presence and localization of the platelet-derived growth factor-receptor-beta
      (PDGF-Rbeta) was investigated in preimplantation bovine and porcine embryos.
      Blastocyst stages before and at the time of elongation were chosen, i.e. 9- to 13
      day-old pig blastocysts and 14- to 16-day-old cattle blastocysts.
      Immunohistochemistry was carried out with monoclonal antibodies directed against
      the beta-chain of the PDGF receptor. Staining was examined by light microscopy.
      PDGF-Rbeta was found in all cell types of the investigated stages in both
      species. Staining was mainly cytoplasmatically with cell membranes most likely
      being positive as well. Staining was very constant in all the stages and cell
      types investigated, except for mesoderm cells and for trophoblast cells adjacent
      to the embryoblast in some pig embryos. Because PDGF-Rbeta is almost
      constitutively expressed in all cell types of bovine and porcine blastocysts, it
      is likely that PDGF participates in cellular differentiation and blastocyst
      elongation preceding implantation in these species.

PMID- 9605604
TI  - Effects of conjugated estrogens with or without medroxyprogesterone acetate on
      mammary carcinogenesis, uterine adenomyosis and femur in mice.
AB  - Although combined hormone replacement therapy using estrogens and progestins
      reduces the risk of endometrial cancer in postmenopausal women, it has been
      unclear whether the combined therapy is associated with an alteration of the risk
      of mammary cancer. Virgin mice of the SHN strain, which has a high potential for
      the development of mammary cancer and uterine adenomyosis, were given diets
      containing conjugated estrogens with or without medroxyprogesterone acetate for
      230 days. The combined administration of conjugated estrogens and
      medroxyprogesterone acetate completely suppressed the development of uterine
      adenomyosis with a decrease in uterine thymidylate synthetase activity,
      significantly enhanced the bone mineral density in the femur and slightly
      shortened the latent period of mammary carcinogenesis.

PMID- 9605605
TI  - Description of two types of mammosomatotropes in mink (Mustela vison)
      adenohypophysis: changes in the population of mammosomatotropes under different
      physiological conditions.
AB  - The present study was undertaken to clarify the existence of mammosomatotropes
      (MS cells) in the mink adenohypophysis and their possible involvement in the
      interconversion of mammotrope and somatotrope cells under different physiological
      conditions: prepubertal, pubertal and adulthood. Electron microscope
      immunocytochemistry was used to detect growth hormone (GH) and prolactin (PRL)
      immunoreactivities in the anterior pituitary gland of mink. Primary antisera
      raised in rabbit (human anti-GH, NIDDK-AFP-1613102481; human anti-PRL, NIDDK-AFP
      55781789) were localized with appropriate species-specific antisera coupled to
      colloidal gold particles of different sizes. MS cells were most frequently
      observed in adult mink. Double labeling for GH and PRL was presented in two types
      of MS cells. MS1 cells, observed only in adults, showed an irregular morphology,
      with many cytoplasmic processes. Within their cytoplasm there were numerous
      rounded secretory granules of approximately 135 nm mean diameter. In MS1 cells
      three types of secretory granules were identified. The most numerous contained
      only PRL. The least frequent contained only GH and the third type contained GH
      and PRL and appeared in an intermediate quantity. MS2 cells, observed in all age
      groups, presented a rounded morphology. These cells had a voluminous cytoplasm
      which showed little development of the organelles and contained a large number of
      rounded and very electron-dense secretory granules which measured about 160 nm
      mean diameter. Within MS2 cells two types of secretory granules, according to
      their immunolabeling, were observed. Monohormonal granules containing GH were the
      more abundant while bihormonal granules, containing GH and PRL, were present to a
      lesser degree. Data presented in this report suggest that MS cells could play a
      role in the interconversion of somatotropes into mammotropes in mink.

PMID- 9605606
TI  - Localization of beta-D-galactosidase activity in semithin epon sections of
      embryonic tissues using differential interference contrast optics.
AB  - In the present study we describe a method for the histochemical demonstration of
      beta-D-galactosidase activity on tissue sections processed for light microscopy
      at high resolution. 5-Bromo-indolyl-beta-D-galactopyranoside (Bluo-Gal) was
      utilized as an indigogenic method for the demonstration of Escherichia coli beta
      D-galactosidase reporter gene activity whose expression was studied in a
      transgenic line where the enzyme, with a nuclear localization signal (nlacZ), is
      under the transcriptional control of a striated muscle-specific promoter. At the
      light-microscopic level, by using Differential Interference Contrast (DIC)
      optics, the reaction product was detected as precipitates in the form of fine
      birefringent crystals. These were located around and inside the nuclei of beta
      gal-expressing cells. This simple method allows an easy and rapid identification
      of few or even one labeled cell(s) within large microscopic fields (whole
      embryos) and the labeled cell(s) can be evaluated both morphologically and
      quantitatively.

PMID- 9605607
TI  - Anatomical partitioning and nerve branching patterns in the adult rabbit
      masseter.
AB  - The masseter muscle is functionally heterogeneous with a complex architecture
      consisting of multiple tendons and a multipennate arrangement of muscle fibers.
      In this study, the anatomical partitioning of the rabbit masseter is described on
      the basis of the tendons of origin and insertion, general partition orientation
      relative to the zygomatic arch, motor endplate descriptions, and primary nerve
      branches that innervate these partitions. This work refines previous descriptions
      of the rabbit masseter and describes 13 anatomical partitions, each with a unique
      tendinous attachment. In addition, 14 naturally occurring primary nerve branches
      were identified and found to innervate different regions of the muscle. After
      correlating the anatomical partitions and the associated neural innervation
      pattern, it was determined that simple branch order will not adequately define
      all the neuromuscular compartments in the rabbit masseter.

PMID- 9605608
TI  - Recommendations for a combined supervision of the fetus during labor by
      cardiotocography, fetal blood analysis and pulse oximetry. A.W. Liley Prize
      lecture at the International Congress 'The Fetus as a Patient', June 1997 in
      Basel.

PMID- 9605609
TI  - Microchimerism and tolerance following intrauterine transplantation and
      transfusion for alpha-thalassemia-1.
AB  - A fetus homozygous for alpha-thalassemia-1 was given haploidentical paternal CD34
      cells at 13, 19 and 24 weeks' gestation and supported through pregnancy by blood
      transfusion. The fetal hematocrit ranged between 27 and 47% and between one half
      and three quarters of this hemoglobin was of recipient (Bart's) type.
      Intrauterine growth proceeded normally and no significant fetal hydrops was
      detected. Tests for donor HLA antigens, and alpha-globin DNA, were negative on
      fetal blood samples drawn before birth. A positive signal for alpha-globin DNA
      was obtained from cord blood and from marrow obtained at 3 months of age,
      suggesting that some donor stem cells had persisted in the recipient. The
      infant's blood mononuclear cells showed little proliferative and no cytotoxic
      response to the donor while responses to a third party were present. Additional
      paternal CD34 cells given at 3 months age did not reduce transfusion dependency
      in the subsequent 6 months. Our results show that repeated transfusions can
      support an alpha-thalassemia-1 fetus through pregnancy, in this instance without
      significant birth defects or apparent hypoxic tissue injury. The donor stem cells
      did not have a survival advantage compared with endogenous stem cells, but
      appeared to survive in the recipient as judged by the persistence of an alpha
      globin DNA signal. In vitro studies of alloreactivity suggest tolerization of the
      host to the donor's MHC disparity. Future efforts will focus on exploiting this
      tolerance to improve the level of donor chimerism.

PMID- 9605610
TI  - Fetal parvovirus B19 infection and meconium peritonitis.
AB  - A 33-year-old primigravida at 26 weeks gestation presented with fetal hydrops and
      fetal anemia following prior parvovirus B19 infection. The fetus required two
      intrauterine transfusions of packed red cells. At 35 weeks gestation, a cesarean
      section was performed for obstetric reasons. As a consequence of a prenatal bowel
      perforation, the neonate developed meconium peritonitis, for which she needed
      laparotomy. This case demonstrates that there may be an association between
      intrauterine parvovirus infection and meconium peritonitis, the latter possibly
      caused by vascular injury in fetal life.

PMID- 9605611
TI  - Postnatal follow-up of hydronephrosis detected by prenatal ultrasound: the
      natural history.
AB  - Babies with hydronephrosis detected antenatally who were born at or referred to
      our hospital from 1990 to 1995 were followed up with ultrasound (U/S),
      micturating cystourethrogram (MCU) or nuclear medicine studies after birth. One
      hundred and three patients were diagnosed antenatally at 17-42 weeks gestation.
      Twelve cases were excluded from the analysis of the results because of incomplete
      data. Fifty-one (56%) patients had hydronephrosis without organic obstruction,
      and 80% of these became normal in 3 years. Fifteen patients (17%) had a normal
      scan 4 days after birth. This suggests the possibility of antenatal spontaneous
      regression. Seven (8%) had a ureterocele and 4 (5%) had pelviureteric junction
      (PUJ) obstruction. Four (5%) had vesicoureteric reflux, and 4 (5%) had primary
      megaureter. Two (2%) had posterior urethral valves (PUV), 3 (3%) had refluxing
      primary megaureter, and 1 (1%) had urethral atresia. Fifteen patients (17%)
      underwent surgical intervention. Six had a nephrectomy, 1 a vesicostomy, 3 an
      Anderson-Hynes pyeloplasty, 3 had the ureterocele unroofed, 1 had a ureteric
      reimplant, and 1 ablation of valves. In 42 infants with 60 abnormal kidneys, the
      renal anteroposterior diameter of the pelvis was measured. Retrospectively, 48
      kidneys diagnosed as having hydronephrosis, antenatally had a renal pelvis
      diameter > or = 4 mm before 33 weeks gestation or > or = 7 mm after 33 weeks
      gestation. One patient with PUJ obstruction lost kidney function, but there is no
      good marker to detect these patients. Early unroofing of ureteroceles may rescue
      kidney function. Our follow-up protocol for antenatal hydronephrosis is U/S at 4
      days, 1 month and 1 year of age. An MCU is not required unless the ureter is seen
      on antenatal U/S. If dilatation persists past 1 month, a radionucleotide (MAG3)
      scan and repeat U/S are performed at 3 months. The methods for assessing
      obstruction and the indications for surgical intervention in these patients
      require reexamination.

PMID- 9605612
TI  - Renal hemodialysis and maternal serum triple analyte screening.
AB  - The obstetrical management of women with renal disease is complicated and
      associated with increased fetal and maternal morbidity. However, maternal serum
      screening is an integral part of obstetrical care and should be offered to all
      women. We found that maternal serum levels of a-fetoprotein and human chorionic
      gonadotropin did not significantly change as a result of hemodialysis, whereas
      levels of unconjugated estriol were markedly decreased following hemodialysis.
      Maternal serum screening should be limited to alpha-fetoprotein analysis in women
      undergoing hemodialysis until the effects of hemodialysis on all serum analytes
      are better delineated.

PMID- 9605613
TI  - Enlarged cisterna magna in the third trimester as a clue to fetal trisomy 18.
AB  - Six of 19 fetuses with trisomy 18 confirmed by late karyotyping in the third
      trimester were found to have an enlarged cisterna magna (10 mm or more). For
      trisomy 18 conceptuses, there is a significant excess of females in both fetuses
      and livebirths; however, we found this ratio to be reversed in the third
      trimester trisomy 18 fetuses with an enlarged cisterna magna (5 males vs. 1
      female), indicating males are more likely to have this associated defect. Each of
      the 6 cases was associated with other trisomy markers including intrauterine
      growth retardation and polyhydramnios. Since a significant proportion of
      pregnancies may escape early prenatal care and some potentially detectable fetal
      abnormalities may be missed on early ultrasound and/or by maternal serum
      screenings, prenatal detection of an enlarged cisterna magna associated with
      intrauterine growth retardation and/or polyhydramnios in late gestation should
      prompt complete genetic counseling, rapid karyotyping and a careful search for
      other congenital anomalies.

PMID- 9605614
TI  - Prenatal diagnosis of a lethal multiple pterygium syndrome type II. Case report.
AB  - Advances in ultrasound technology and sonographer's experience lead to the
      description of many rare syndromes and malformations through prenatal diagnosis.
      Diaphragmatic hernia is a rather common malformation but can be an indicator of
      different syndromes. We report the prenatal diagnosis of lethal multiple
      pterygium syndrome type II which has been established in the 34th week of
      pregnancy. The sonographically detectable symptoms consisted of polyhydramnios,
      hygroma colli, diaphragmatic hernia, scoliosis, short forearms, hypokinesia of
      the fetus and pterygia over the large joints. Labour was induced in the 34th week
      of pregnancy; the neonate died shortly after vaginal delivery as a result of the
      pulmonary hypoplasia. A multidisciplinary approach in prenatal assessment may
      help to clarify difficult diagnostic problems and may be of direct benefit for
      the pregnant patient.

PMID- 9605615
TI  - A case with duodenal duplication cyst: prenatal diagnosis and surgical
      management.
AB  - OBJECTIVE: We report the first case of a subhepatic cystic mass diagnosed in
      utero that subsequently proved to be a duodenal duplication cyst. METHOD:
      Conventional prenatal abdominal ultrasound. RESULTS: On prenatal ultrasonography,
      the differential diagnosis was choledochal cyst, bowel duplication cyst, or
      omental cyst. CONCLUSION: The prenatal detection of a cystic mass allowed close
      neonatal surveillance and timely surgical intervention prior to the onset of
      potentially serious complications.

PMID- 9605616
TI  - Analysis of the origin of the extra chromosome in trisomy 8 in 4 cases of
      spontaneous abortions.
AB  - OBJECTIVE: To determine the origin of the extra chromosome in trisomy 8 in
      spontaneous abortions. METHODS: We analyzed 4 cases of nonmosaic trisomy 8 in 1st
      trimester spontaneous abortions and their parents with DNA polymorphism analysis
      using microsatellite DNA markers. RESULTS: In 3 cases the extra chromosome was
      maternal in origin and in 1 case paternal in origin. In 2 of the cases the
      nondisjunction had occurred in maternal meiosis, while the other 2 cases were
      consistent with a postzygotic (mitotic) origin of the additional chromosome.
      CONCLUSION: Although a small number of cases studied, these results suggest
      differences from the common autosomal trisomies 21, 18, 16, and 13 where the vast
      majority of cases are due to errors in maternal meiosis.

PMID- 9605617
TI  - Maternal weight differences do not explain ethnic differences in biochemical
      screening.
AB  - In previous work, we and others have shown that serum levels of alpha
      fetoprotein, human chorionic gonadotropin, and estriol vary among the four
      commonly defined racial/ethnic groups seen in the United States: white, African
      American, Asian, and Hispanic. We have suggested that better sensitivity and
      specificity could improve screening sensitivity and specificity. However, it has
      been argued that systematic weight differences among the groups could explain the
      variation. We evaluated the results from 208,257 patients having screening and
      found systematic weight differences. However, these differences were not as large
      as the racial/ethnic differences, showing that weight does not fully explain the
      discrepancy, and, therefore, four separate data bases give more accurate results.

PMID- 9605618
TI  - The apparently isolated choroid plexus cyst: importance of minor abnormalities in
      predicting the risk for aneuploidy.
AB  - OBJECTIVES: To assess the risk of aneuploidy in cases of isolated choroid plexus
      cysts (CPCs) and to compare the risk when associated with minor or major
      anomalies. METHODS: All fetuses with CPCs and known karyotype were identified.
      CPCs were categorized as 'isolated' or associated with minor or major sonographic
      anomalies. Preexisting risk factors for aneuploidy were compared between groups.
      The frequency of aneuploidy was compared between fetuses with isolated CPCs and
      those with CPCs associated with minor or major anomalies. Continuous and
      categorical variables were analyzed using one-way analysis of variance or chi
      square as appropriate with p < 0.05 considered significant. RESULTS: One hundred
      and forty-nine fetuses with CPCs diagnosed at a mean gestational age of 19 weeks
      were identified. No significant differences in the frequency of preexisting risk
      factors for aneuploidy were identified between groups. Eighteen of 149 (12%)
      fetuses with CPCs had other sonographic anomalies; in 10 they were minor, and 2
      of the 10 had abnormal karyotypes. Four of 8 fetuses with major anomalies were
      aneuploid. All 131 fetuses with isolated CPCs had normal karyotypes, and all
      aneuploid fetuses had additional anomalies. CONCLUSIONS: The overall rate of
      aneuploidy in patients with CPCs was 4% with no abnormal karyotypes among
      isolated CPCs. The presence of even minor sonographic abnormalities substantially
      increased the risk of aneuploidy. Isolated CPCs identified sonographically may
      not place the patient at risk of aneuploidy, but should prompt a diligent search
      for other minor or major anomalies. The finding of any other anomaly warrants
      consideration for karyotypic evaluation.

PMID- 9605619
TI  - Factors influencing informed choice of prenatal diagnosis: women's feelings and
      attitudes.
AB  - OBJECTIVE: To obtain knowledge about factors that could influence women's
      informed choice and extent of prenatal diagnosis, her feelings when implementing
      it, and her satisfaction. METHOD: A questionnaire including Visual Analogue Scale
      was given to 823 women and replies received from 662 (80.4%). Ease of choice was
      the basis for the statistical analysis. RESULTS: The factors that most often
      influenced choice were the fetus health, maternal age, and knowledge of the
      consequences. The choice was easy to make, only 2% finding it very difficult. The
      time period from the amniocentesis until the results were available was the most
      difficult time reported. CONCLUSIONS: The choice of method for prenatal diagnosis
      was very easy for most women. Satisfaction with choice was high (98%). Extra
      support can be needed while awaiting results of invasive prenatal diagnosis.

PMID- 9605620
TI  - Electromolecular propulsion (EMP): a rapid, simple method for analyzing dyes used
      in microscopy.
AB  - The electrokinetic molecular effect known as electromolecular propulsion (EMP)
      was used to examine a variety of commonly used dyes that are used as biological
      stains. The dyes were electrokinetically mobilized using several organic solvent
      mixtures on a variety of thin layer substrates. Analysis was completed in seconds
      to minutes. Nearly all dyes tested separated into multiple colored components.
      The solvents and substrates used were well suited for qualitatively analyzing a
      broad variety of hydrophilic and lipophilic colorants. Speed, resolving power and
      operational simplicity of this technique make it convenient for effectively
      "fingerprinting" for consistency in dye products. EMP may be broadly applied to
      study quality control of dyes and their stains. Components not ordinarily known
      to be present can be readily detected using this technology. EMP can complement
      or offer a versatile alternative to existing analytical methods.

PMID- 9605621
TI  - Sirius red and acid fuchsin staining mechanisms.
AB  - The purpose of the study was to investigate the staining mechanism of acid
      fuchsin and Sirius red. Acid (poly-glutamic acid), neutral (poly-hydroxyproline)
      and basic (poly-arginine, poly-histidine, poly-lysine) poly-amino acids, collagen
      types I, II and III, and arginine- and lysine-containing histones were used as
      test substances applied to nitrocellulose membranes as dot blots. Five micrometer
      sections of granulation tissue on slides were tested in parallel. Some dots and
      sections were treated with chloramine-T before staining with acid fuchsin and
      Sirius red and some with 1 M NaOH after staining. The acid and neutral poly-amino
      acids were not stained, but the basic amino acids polylysine and poly-arginine,
      poly-amino acids containing these basic amino acids and the histones and the
      collagens exhibited intense staining. Oxidative deamination by chloramine-T
      abolished the staining and 1 M NaOH removed the staining except in the case of
      poly-arginine. Tissue sections treated in the same way showed a considerable
      decrease in staining after oxidative deamination with chloramine-T; in
      particular, the staining of the smaller fibers was abolished. The staining was
      totally removed by destaining with 1 M NaOH. Therefore, acid fuchsin and Sirius
      red are not selectively bound to collagen; they are also bound to other proteins
      containing basic amino acids, and staining to a large extent is influenced by
      electrostatic forces. The staining seems not to be selective for collagen, and
      one must account for this when quantitative conclusions are drawn from collagen
      methods using these stains.

PMID- 9605622
TI  - Improved hematoxylin staining for algal cytogenetics.
AB  - The aceto-iron hematoxylin method of Wittmann for algal chromosomes was improved
      by replacing the chloral hydrate and slide heating steps with 5 N HCl hydrolysis.
      Squashing of the unstained material under the coverslip followed by coverslip
      removal and air drying allowed rapid and more homogeneous staining. Additional
      procedures were developed to make the method easier and quicker. Good results
      were obtained for all algal species analyzed. Pit-connections of red algae were
      also clearly differentiated.

PMID- 9605623
TI  - Stimulation of rat peritoneal mast cells induces phagocytosis of adriamycin by
      rat peritoneal macrophages.
AB  - Rat and beige mouse peritoneal mast cells, induced to exocytose with the
      antineoplastic agent adriamycin, extrude their granule remnants in the
      extracellular medium. These granules are loaded with the fluorescent drug
      adriamycin and exhibit intense yellow-reddish fluorescent staining. Granules
      extruded from mast cells were ultimately phagocytosed and could be observed
      inside the macrophages by fluorescence microscopy. All stages of the
      internalization process could be followed by electron microscopy. Granules
      adhering to the cell surface of macrophages were first embraced by short
      superficial projections, then enveloped by deep surface infoldings, and finally
      engulfed into the macrophage cytoplasm. Phagocytosis occurred exclusively in
      macrophages; granules were observed also on the surface of eosinophils and
      lymphocytes, but never inside these cells. The concentrations of adriamycin in
      macrophages, measured by spectrofluorimetry, were significantly higher when these
      cells were incubated with adriamycin and granule remnants in comparison with
      adriamycin alone. Preincubation with the endocytosis inhibitor cytochalasin B
      significantly reduced the granule mediated adriamycin uptake. As a consequence of
      the phagocytosis of adriamycin loaded mast cell granules, macrophages can
      concentrate the antineoplastic drug. These cells act as reservoirs of adriamycin
      and could have an important role in both the antitumor and toxic effects of the
      drug.

PMID- 9605624
TI  - A squash preparation method for root meristem field studies.
AB  - We present a field method for squash preparation of root apical meristem that
      does not require dry ice for cell adhesion to a slide. The method is based on the
      use of a weak gelatin solution as a stabilizing agent to prevent cell loss.
      Alcian blue 8GX was used as a counterstain for better recognition of cell shapes.
      Root meristems of Sonoran Desert succulents were used to illustrate the method.
      Fixed root tips were stained by Feulgen and squashes were prepared in a 1:2
      mixture of solution A (45% acetic acid) and solution B (3:1 mixture of 0.5%
      gelatin in water:0.02% of alcian blue 8GX in 45% acetic acid). After squashing,
      the material was lightly dried for 5-6 min, then dehydrated and mounted in Canada
      balsam. Our method permits observation of chromosomes, recognition of
      meristematic and nonmeristematic cells, and estimation of mitotic indices and
      thus recognition of growing, dormant, and dead roots. The method can be used for
      estimation of cell division cycle time by colchicine and other methods where
      squash preparation is required.

PMID- 9605625
TI  - Determination of epidermal transpiration in four cultivars of Nicotiana tabacum
      L. using epidermal strips in a quasi-steady state system.
AB  - A quasi-steady state method is presented for quantifying epidermal transpiration
      of epidermal strips where simple relations between transmembrane fluxes and
      parameters of diffusibility of penetrating compounds hold. Contrary to most
      permeability studies, we did not use astomatous, enzymatically isolated, or dried
      cuticular membranes, because these procedures are largely responsible for the
      problems cited in the literature. Instead, we used freshly harvested stomatous
      epidermal strips, thus avoiding the sorption of lipids by the cuticular membranes
      during enzymatic isolation. Our approach allowed estimation of amounts and
      composition of intracuticular soluble lipids. Diffusion coefficients (D-values)
      were calculated with smaller associated standard deviations and an order of
      magnitude lower than previously reported; the fresh material sorption of the
      diffusing compound by the membrane and hydration of the cuticular pores was
      greatly reduced. In the present study the hold-up time (te) ranged from 66.2+/
      0.3 to 110.3+/-0.9 sec. Furthermore, 0.1 microm thick membranes were used,
      contrary to previous studies of water permeability that used cuticles more than 2
      microm thick. Because a small but constant flow of penetrant could be detected
      during the first half of the steady flow to te, small holes probably did not
      influence the reported permeability. Permeability coefficients (Pd) in the order
      of 0.65 x 10(-9) ms(-1) were calculated. Pd values in the order of 5.68 x 10(-3)
      ms(-1) were calculated when incomplete stomatal closure occurred, while when
      areas of mass flow were detected, Pd values in the order of 1.26 x 10(-2) ms(-1)
      were calculated. The degree of contamination of the epidermal strips by cellular
      debris was quantified and expressed as the total chlorphyll content per exposed
      surface area of the epidermal strip, and an average of 8.7% contamination was
      observed compared to the total leaf chlorophyll content. Leakage from the system
      was calculated to be approximately 0.18 x 10(-10) ms(-1), which represents an
      average 2.7% experimental variability. These results are discussed in terms of
      the limitations associated with using composite membranes that are stomatous and
      have trichomes, for possible application in drought tolerance selection.

PMID- 9605626
TI  - Comparison of staining techniques for scanning electron microscopic detection of
      ultrastructural protuberances on cellulolytic bacteria.
AB  - Cell surface protuberances found on cellulolytic bacteria, but not on
      noncellulolytic bacteria, can be detected by scanning electron microscopy.
      Cationized ferritin typically has been used as a stain to increase the
      microscopic resolution of these protuberances; however, as a cation it binds only
      to negatively charged molecules. Thus, binding of cationized ferritin to cell
      surface molecules can be affected by the cell's physiological state. We incubated
      the noncellulolytic bacterium, Clostridium beijerinckii, in different media at
      various temperatures to obtain cells with different growth rates and
      physiological states. Staining of these cells with cationized ferritin showed
      that slower growing cells exhibited more protuberant structures than faster
      growing cells. This provided a clear correlation of ultrastructural protuberances
      with physiological changes associated with growth rate. On the other hand, cells
      stained with osmium tetroxide exhibited no protuberant structures regardless of
      growth rate. Because various cations are known to induce aggregation of surface
      proteins on some cellulolytic Clostridia, we incubated the cellulolytic
      bacterium, Clostridium cellulovorans, in media containing glucose, cellobiose, or
      cellulose. Ultrastructural protuberances were evident on all cells stained with
      cationized ferritin, but extensive protuberances were detected only on cells
      grown in cellulose and stained with osmium tetroxide. For cells stained with
      cationized ferritin, the presence of ultrastructural protuberances was correlated
      with growth rate rather than induction of cellulolytic systems. By contrast,
      cells stained with osmium tetroxide showed a clear correlation between
      protuberant structures and cellulolytic activity.

PMID- 9605627
TI  - Beta-cell autoimmunity 1998.

PMID- 9605628
TI  - Immunology in diabetes: an update.
AB  - Type 1 (insulin-dependent) diabetes mellitus is strongly associated with
      autoimmune phenomena connected to the loss of beta-cells in the pancreatic
      islets. Despite considerable progress in our understanding of genetic
      susceptibility factors and islet autoimmunity preceding the clinical onset of
      Type 1 diabetes there are considerable gaps in our knowledge. First, the etiology
      is unclear. It is speculated that multiple etiological factors may initiate a
      common pathogenic pathway which results in immune-mediated beta-cell destruction.
      In 1998 we will need to learn more about the possible importance of gestational
      infections, as well as isolation of viral DNA or RNA from the blood of new-onset
      patients or marker-positive individuals. The scan of the whole genome has
      provided a smorgasbord of genetic regions which confer diabetes risk either alone
      or in combination. HLA remains the major genetic risk factor, and while HLA
      peptide binding information is considerable, we understand less of autoantigen
      processing and presentation. Cloned autoantigens and their use in standardized
      autoantibody assays have improved our ability to identify individuals at risk for
      diabetes. The diagnostic sensitivity and specificity of autoantibody markers for
      Type 1 diabetes are high as are their predictive values. We need methods to
      combine autoantibodies with genetic risk factors. The identification of
      individuals in different stages of their pathogenesis, including patients with so
      called slowly progressive Type 1 diabetes (SPIDDM, LADA etc.), allow approaches
      to novel therapeutic interventions. Insulin is currently the therapeutic agent of
      choice and although spontaneous insulin-dependent diabetes in the NOD mouse and
      the BB rat can be prevented by immune suppression or modulation, this has not yet
      been possible in humans. The 1998 research on the interaction between
      environmental factors and susceptibility genes to initiate beta-cell specific
      autoreactivity should allow the development of therapies for prevention, and
      perhaps a cure, of insulin-dependent (Type 1) diabetes.

PMID- 9605629
TI  - Putative environmental factors in Type 1 diabetes.
AB  - Various environmental triggers, e.g. certain viruses and dietary factors, are
      thought to initiate the autoimmune process, leading to the destruction of
      pancreatic beta-cells and consequent Type 1 diabetes. A genetic predisposition is
      another prerequisite allowing the autoimmune process to progress. Twin studies,
      major geographical variations in incidence rates, temporal trends in the
      incidence and findings in migrant studies indicate that environmental factors
      play a crucial role in the development of Type 1 diabetes. In the present review
      the major focus is on dietary factors, and among them particularly the possible
      role of cow's milk proteins. The cow's milk and Type 1 diabetes hypothesis was
      developed more than 10 years ago, and the issue is still not settled. Among viral
      infections, enteroviruses are today the most interesting group of viruses in this
      respect, as recent prospective studies indicate that these viruses may trigger
      and potentiate existing beta-cell autoimmunity. Among toxins, particularly N
      nitroso compounds are of potential interest, as they are probably involved in the
      aetiology of some cases. Finally, psychosocial factors and the interaction
      between genetic predisposition and environmental factors are briefly discussed.

PMID- 9605630
TI  - Prevention of insulin-dependent diabetes mellitus 1998.
AB  - Recent advances in the understanding of the pathogenesis of insulin-dependent
      diabetes mellitus (IDDM) have led to the first trials of disease prevention in
      susceptible individuals. Two main trials (nicotinamide and insulin) are now
      running but first results will not be available before the turn of the century.
      Pilot trials using different approaches, most of them based on the induction of
      immunotolerance, are also under way and should offer new insight for establishing
      larger multicentre studies including attempts aimed at primary prevention by
      removal of diabetogenic components in cow's milk. The field is moving fast and it
      is expected that intervention for IDDM prevention will be offered to an
      increasing number of individuals found at risk of developing the disease.

PMID- 9605631
TI  - IA-2 and IA-2beta: the immune response in IDDM.
AB  - Pancreatic islet cell autoantigens associated with insulin-dependent diabetes
      mellitus (IDDM) include a recently identified family of protein tyrosine
      phosphatase-like molecules, notably IA-2 and IA-2beta. IA-2 is a 979 amino acid
      transmembrane protein located on human chromosome 2q35, whereas IA-2beta is 986
      amino acids long located on human chromosome 7q36. Comparison of human IA-2 and
      IA-2beta showed 74% identity within the intercellular domains, but only 27%
      indentify within the extracellular domains. These IA-2 molecules are expressed
      predominantly in cells of neuroendocrine origin, particularly pancreatic islets
      and brain. Radioimmunoprecipitation with recombinant IA-2 and IA-2beta has been
      used to measure autoantibodies to these molecules and their intracellular
      fragments. Autoantibodies to IA-2 are detected in the majority (60% to 80%) of
      newly diagnosed IDDM patients and in less than 2% of controls. The major
      antigenic determinants of both IA-2 and IA-2beta reside within the C-terminus of
      their intracellular domains. In first-degree relatives of IDDM patients, the
      presence of autoantibodies to IA-2 is predictive of IDDM and in combination with
      autoantibodies to glutamic acid decarboxylase (GAD) the positive predictive value
      is in the 50% range. The role of IA-2 and IA-2beta in the pathogenesis of IDDM is
      still unclear. Identification of these antigens has extended our ability to
      predict the disease and may be valuable in the search for antigen-specific
      therapies to prevent IDDM.

PMID- 9605632
TI  - The intrathymic expression of insulin-related genes: implications for
      pathophysiology and prevention of Type 1 diabetes.
AB  - Recent experimental work has challenged and shattered the old concept of a
      sequestration of pancreatic islet antigens from developing T-cells within the
      thymic environment. There is now compelling evidence that the central
      immunological tolerance of the whole insulin family may be induced during the
      process of T-cell ontogeny in the thymus. Transcripts of insulin-like growth
      factor II (IGF-II), IGF-I and insulin genes have been characterized in human, rat
      and mouse thymuses. At the peptide level, IGF-II was shown to be the dominant
      polypeptide of the insulin family in the thymus from different species. Data are
      presented which support a dual role of thymic IGF-II both in T-cell development
      as well as in T-cell negative selection. Using animal models of autoimmune
      diabetes, current research is investigating the hypothesis that a defect of
      thymic T-cell education to the insulin family is implicated in the
      pathophysiology of human Type 1 diabetes. An efficient and secure prevention of
      Type 1 diabetes could be designed on the basis of the strong natural tolerogenic
      properties of the thymus.

PMID- 9605633
TI  - Dietary intervention for diabetes prevention in the neonate.

PMID- 9605634
TI  - The trouble with neonates...

PMID- 9605635
TI  - Intervention at neonatal age: can we intervene?

PMID- 9605636
TI  - Intervention for diabetes prevention at neonatal age.

PMID- 9605637
TI  - Does a clinical trial warrant an economic analysis?

PMID- 9605638
TI  - Protective effect of cigarette smoking on breast cancer risk in women with BRCA1
      or BRCA2 mutations???

PMID- 9605639
TI  - Sentinel node biopsy: studies should bring needed data.

PMID- 9605640
TI  - Post-mastectomy pain found to be common: treatment options sparse, but growing.

PMID- 9605641
TI  - New guidelines may unify cancer pain management.

PMID- 9605642
TI  - Global cancer burden difficult to assess, rising rates likely.

PMID- 9605643
TI  - Automation and the endangered future of the Pap test.

PMID- 9605644
TI  - Cost-minimization analysis of prophylactic granulocyte colony-stimulating factor
      after induction chemotherapy in children with non-Hodgkin's lymphoma.
AB  - BACKGROUND: Colony-stimulating factors promote the proliferation of certain bone
      marrow cell populations. The primary objective of treating patients with these
      factors prophylactically following chemotherapy is to reduce the risk of
      infection, thereby minimizing the need for hospitalization and parenteral
      antibiotics. The use of colony-stimulating factors in children is widespread,
      despite the absence of conclusive supportive data and the high cost of these
      drugs. Consequently, the cost-benefit ratio of using prophylactic colony
      stimulating factors is an important issue in cancer therapy. METHODS: During the
      period from January 1994 through June 1996, 149 afebrile children with newly
      diagnosed non-Hodgkin's lymphoma were randomly assigned either to receive
      granulocyte colony-stimulating factor (G-CSF) (lenograstim; 5 microg/kg body
      weight per day subcutaneously) or not to receive it (the control) at the end of
      the first two courses of induction chemotherapy with cyclophosphamide,
      vincristine, prednisone, doxorubicin, and methotrexate. A cost-minimization
      analysis was performed to assess the cost of chemotherapy in each group and to
      quantify how much could be economized by prescribing G-CSF. RESULTS: The total
      cost for induction chemotherapy was $29,765 in the G-CSF-treated group and
      $30,774 in the control group, indicating that the treatment strategy with G-CSF
      was slightly less expensive than the strategy without G-CSF (mean difference =
      $1009; 95% confidence interval = -$1474 to $3492). CONCLUSION: Treatment with G
      CSF following chemotherapy in children with non-Hodgkin's lymphoma--previously
      shown to be of limited clinical benefit--also does not appear to reduce the costs
      of chemotherapy.

PMID- 9605645
TI  - Clinical characteristics and biopsy specimen features in African-American and
      white men without prostate cancer.
AB  - BACKGROUND: The reported incidence of prostate cancer is higher among African
      American men than among white men. We conducted a study of African-American and
      white men without prostate cancer to determine whether clinical and histologic
      findings might be associated with racial differences in serum prostate-specific
      antigen (PSA) levels. METHODS: From January 1990 through March 1997, 493 (59.5%)
      of 829 African-American men and 736 (74.1%) of 993 white men who had elevated
      serum PSA levels (> or = 4.0 ng/mL) and/or abnormal digital rectal examinations
      and who underwent transrectal ultrasound-guided prostate biopsies were found to
      be without prostate cancer. Also reviewed were patients' age and race, indication
      for biopsy, histologic features of the prostate biopsy specimen, ultrasound
      measured prostate volume, PSA density (i.e., the PSA level divided by the
      prostate volume), and (in some cases) serum testosterone levels. RESULTS: Among
      these men without prostate cancer, there were no statistically significant
      differences by race in the ages of the patients, their prostate volumes, or their
      serum testosterone levels; however, the mean serum PSA levels and PSA densities
      were significantly higher in African-American men than in white men (two-sided P
      values of .00003 and .000009, respectively). A higher proportion of African
      American men than white men had inflammation in their prostate biopsy specimen,
      and men of both races with prostate inflammation had higher PSA values than those
      without inflammation. African-American men without inflammation had higher PSA
      values than white men without inflammation. CONCLUSIONS: In this study, African
      American men without histologic evidence of prostate cancer had significantly
      higher PSA levels and PSA densities than similarly aged white men. This finding
      was not accounted for by racial differences in patients' age, serum testosterone
      level, or prostate volume.

PMID- 9605646
TI  - Effect of smoking on breast cancer in carriers of mutant BRCA1 or BRCA2 genes.
AB  - BACKGROUND: Smoking has carcinogenic effects, and possibly antiestrogenic effects
      as well, but it has not been found to be a risk factor for breast cancer in women
      in the general population. However, hereditary breast cancer is primarily a
      disease of premenopausal women, and interactions between genes and hormonal and
      environmental risk factors may be particularly important in this subgroup.
      METHODS: We conducted a matched case-control study of breast cancer among women
      who have been identified to be carriers of a deleterious mutation in either the
      BRCA1 or the BRCA2 gene. These women were assessed for genetic risk at one of
      several genetic counseling programs for cancer in North America. Information
      about lifetime smoking history was derived from a questionnaire routinely
      administered to women who were found to carry a mutation in either gene. Smoking
      histories of case subjects with breast cancer and age-matched healthy control
      subjects were compared. Odds ratios for developing breast cancer were determined
      for smokers versus nonsmokers by use of conditional logistic regression for
      matched sets after adjustment for other known risk factors. RESULTS: Subjects
      with BRCA1 or BRCA2 gene mutations and breast cancer were significantly more
      likely to have been nonsmokers than were subjects with mutations and without
      breast cancer (two-sided P = .007). In a multivariate analysis, subjects with
      BRCA1 or BRCA2 mutations who had smoked cigarettes for more than 4 pack-years
      (i.e., number of packs per day multiplied by the number of years of smoking) were
      found to have a lower breast cancer risk (odds ratio = 0.46, 95% confidence
      interval = 0.27-0.80; two-sided P = .006) than subjects with mutations who never
      smoked. CONCLUSIONS: This study raises the possibility that smoking reduces the
      risk of breast cancer in carriers of BRCA1 or BRCA2 gene mutations.

PMID- 9605647
TI  - A preoperative nomogram for disease recurrence following radical prostatectomy
      for prostate cancer.
AB  - BACKGROUND: Few published studies have combined clinical prognostic factors into
      risk profiles that can be used to predict the likelihood of recurrence or
      metastatic progression in patients following treatment of prostate cancer. We
      developed a nomogram that allows prediction of disease recurrence through use of
      preoperative clinical factors for patients with clinically localized prostate
      cancer who are candidates for treatment with a radical prostatectomy. METHODS: By
      use of Cox proportional hazards regression analysis, we modeled the clinical data
      and disease follow-up for 983 men with clinically localized prostate cancer whom
      we intended to treat with a radical prostatectomy. Clinical data included
      pretreatment serum prostate-specific antigen levels, biopsy Gleason scores, and
      clinical stage. Treatment failure was recorded when there was clinical evidence
      of disease recurrence, a rising serum prostate-specific antigen level (two
      measurements of 0.4 ng/mL or greater and rising), or initiation of adjuvant
      therapy. Validation was performed on a separate sample of 168 men, also from our
      institution. RESULTS: Treatment failure (i.e., cancer recurrence) was noted in
      196 of the 983 men, and the patients without failure had a median follow-up of 30
      months (range, 1-146 months). The 5-year probability of freedom from failure for
      the cohort was 73% (95% confidence interval = 69%-76%). The predictions from the
      nomogram appeared accurate and discriminating, with a validation sample area
      under the receiver operating characteristic curve (i.e., comparison of the
      predicted probability with the actual outcome) of 0.79. CONCLUSIONS: A nomogram
      has been developed that can be used to predict the 5-year probability of
      treatment failure among men with clinically localized prostate cancer treated
      with radical prostatectomy.

PMID- 9605648
TI  - Effect of dehydroepiandrosterone and the antiestrogen EM-800 on growth of human
      ZR-75-1 breast cancer xenografts.
AB  - BACKGROUND: In the mammary gland, androgens are formed from the precursor steroid
      dehydroepiandrosterone (DHEA). Clinical evidence indicates that androgens have
      inhibitory effects on breast cancer. Estrogens, on the other hand, stimulate the
      development and growth of breast cancer. We studied the effect of DHEA alone or
      in combination with the newly described pure antiestrogen EM-800 on the growth of
      subcutaneous tumor xenografts formed by the human breast cancer cell line ZR-75-1
      in ovariectomized nude mice. METHODS: Immediately after ovariectomy, mice
      received daily subcutaneous injections of 0.5 microg estrone (E1) (an estrogenic
      hormone). EM-800 (15, 50, or 100 microg) was given orally once daily. DHEA was
      administered percutaneously twice daily (total dose of 0.3, 1.0, or 3.0 mg) to
      the dorsal skin either alone or in combination with a 15-microg daily oral dose
      of EM-800. Changes in tumor size in response to the treatments (in relation to
      measurements made on the first day of treatment) were assessed periodically. At
      the end of the experiments, tumors were dissected and weighed. RESULTS: A 9.4
      fold increase in tumor size in 9.5 months was observed in ovariectomized mice
      receiving E1 alone. Administration of 15, 50, or 100 microg EM-800 in E1
      supplemented mice led to inhibitions of 87.5%, 93.5%, and 94.0% in tumor size,
      respectively. DHEA, on the other hand, at doses of 0.3, 1.0, or 3.0 mg inhibited
      terminal tumor size by 50.4%, 76.8%, and 80.0%, respectively. Comparable
      inhibitions in tumor size were obtained with a daily 15-microg oral dose of EM
      800 with or without different doses of percutaneous DHEA. CONCLUSIONS: DHEA and
      EM-800 independently suppressed the growth of E1-stimulated ZR-75-1 xenograft
      tumors in nude mice. Administration of DHEA at the defined doses did not alter
      the inhibitory effect of EM-800.

PMID- 9605649
TI  - Lack of serologic association between human herpesvirus-8 infection and multiple
      myeloma and monoclonal gammopathies of undetermined significance.

PMID- 9605650
TI  - Detection of gene deletion in single metastatic tumor cells in the excision
      margin of a primary cutaneous melanoma.

PMID- 9605651
TI  - Re: Cigarette smoking and changes in the histopathology of lung cancer.

PMID- 9605652
TI  - Presidential Address. Transitions.

PMID- 9605653
TI  - Elective bedside surgery in critically injured patients is safe and cost
      effective.
AB  - OBJECTIVE: The success of elective minimally invasive surgery suggested that this
      concept could be adapted to the intensive care unit. We hypothesized that
      minimally invasive surgery could be done safely and cost-effectively at the
      bedside in critically injured patients. SUMMARY BACKGROUND DATA: This case
      series, conducted between October 1991 and June 1997 at a Level I trauma center,
      examined bedside dilatational tracheostomy (BDT), percutaneous endoscopic
      gastrostomy (PEG), and inferior vena cava (IVC) filter placement. All procedures
      had been performed in the operating room (OR) before initiation of this study.
      METHODS: All BDTs and PEGs were performed with intravenous general anesthesia
      (fentanyl, diazepam, and pancuronium) administered by the surgical team. IVC
      filters were placed using local anesthesia and conscious sedation. BDTs were done
      using a Ciaglia set, PEGs were done using a 20 Fr Flexiflow Inverta-PEG kit, and
      IVC filters were placed percutaneously under ultrasound guidance. Cost difference
      (delta cost) was defined as the difference in hospital cost and physician charges
      incurred in the OR as compared to the bedside. RESULTS: Of 16,417 trauma
      admissions, 379 patients (2%) underwent 472 minimally invasive procedures (272
      BDTs, 129 PEGs, 71 IVC filters). There were four major complications (0.8%). Two
      patients had loss of airway requiring reintubation. Two patients had an
      intraperitoneal leak from the gastrostomy requiring operative repair. No patient
      had a major complication after IVC filter placement. Total delta cost was
      $611,994. When examined independently, the cost was $324,224 for BDT, $164,088
      for PEG, and $123,682 for IVC filter. OR use was reduced by 506 hours.
      CONCLUSIONS: These bedside procedures have minimal complications, eliminate the
      risk associated with patient transport, reduce cost, improve OR utilization, and
      should be considered for routine use in the general surgery population.

PMID- 9605654
TI  - Adaptive alterations in cellular metabolism with malignant transformation.
AB  - OBJECTIVE: The authors studied the differences between glutamine and glucose
      utilization in normal fibroblasts and in fibrosarcoma cells to gain insights into
      the metabolic changes that may occur during malignant transformation. SUMMARY
      BACKGROUND DATA: The process of malignant transformation requires that cells
      acquire and use nutrients efficiently for energy, protein synthesis, and cell
      division. The two major sources of energy for cancer cells are glucose and
      glutamine. Glutamine is also essential for protein and DNA biosynthesis. We
      studied glucose and glutamine metabolism in normal and malignant fibroblasts.
      METHODS: Studies were done in normal rat kidney fibroblasts and in rat
      fibrosarcoma cells. We measured glutamine transport across the cell membrane,
      breakdown of glutamine by the enzyme glutaminase (the first step in oxidation),
      glutamine and glucose oxidation rates to CO2, rates of protein synthesis from
      glutamine, and glutamine-dependent growth rates. RESULTS: Glutamine transport
      rates were increased more than sixfold in fibrosarcomas compared to normal
      fibroblasts. In fibroblasts, glutamine transport was mediated by systems ASC and
      A. In malignant fibrosarcomas, only system ASC was identifiable, and its Vmax was
      15 times higher than that observed in fibroblasts. Despite an increase in
      transport, glutaminase activity was diminished and glutamine oxidation to CO2 was
      reduced in fibrosarcomas versus normal fibroblasts. In fibroblasts, glutamine
      oxidation was 1.8 times higher than glucose oxidation. In contrast, glucose
      oxidation was 3.5 times greater than glutamine oxidation in fibrosarcomas.
      Protein synthesis from glutamine transported by fibrosarcomas was threefold
      greater than that observed in normal fibroblasts. Despite marked increases in
      glutamine utilization and glucose oxidation in fibrosarcoma cells, growth rates
      were higher in the normal fibroblasts. CONCLUSIONS: The process of malignant
      transformation is associated with a marked increase in cellular glutamine
      transport, which is mediated by a single high-affinity, high-capacity plasma
      membrane carrier protein. In normal fibroblasts, the transported glutamine is
      used primarily for energy production via oxidation of glutamine carbons to CO2.
      In fibrosarcomas, glutamine oxidation falls and glutamine is shunted into protein
      synthesis; simultaneously, the malignant cell switches to a glucose oxidizer. The
      increased glutamine transport and glucose oxidation in fibrosarcomas appears to
      be related to the malignant phenotype and not merely to an increase in cell
      growth rates.

PMID- 9605655
TI  - A new paradigm for type 2 diabetes mellitus: could it be a disease of the
      foregut?
AB  - SUMMARY BACKGROUND DATA: We previously reported, in a study of 608 patients, that
      the gastric bypass operation (GB) controls type 2 diabetes mellitus in the
      morbidly obese patient more effectively than any medical therapy. Further, we
      showed for the first time that it was possible to reduce the mortality from
      diabetes; GB reduced the chance of dying from 4.5% per year to 1% per year. This
      control of diabetes has been ascribed to the weight loss induced by the
      operation. These studies, in weight-stable women, were designed to determine
      whether weight loss was really the important factor. METHODS: Fasting plasma
      insulin, fasting plasma glucose, minimal model-derived insulin sensitivity and
      leptin levels were measured in carefully matched cohorts: six women who had
      undergone GB and had been stable at their lowered weight 24 to 30 months after
      surgery versus a control group of six women who did not undergo surgery and were
      similarly weight-stable. The two groups were matched in age, percentage of fat,
      body mass index, waist circumference, and aerobic capacity. RESULTS: Even though
      the two groups of patients were closely matched in weight, age, percentage of
      fat, and even aerobic capacity, and with both groups maintaining stable weights,
      the surgical group demonstrated significantly lower levels of serum leptin,
      fasting plasma insulin, and fasting plasma glucose compared to the control group.
      Similarly, minimal model-derived insulin sensitivity was significantly higher in
      the surgical group. Finally, self-reported food intake was significantly lower in
      the surgical group. CONCLUSIONS: Weight loss is not the reason why GB controls
      diabetes mellitus. Instead, bypassing the foregut and reducing food intake
      produce the profound long-term alterations in glucose metabolism and insulin
      action. These findings suggest that our current paradigms of type 2 diabetes
      mellitus deserve review. The critical lesion may lie in abnormal signals from the
      gut.

PMID- 9605656
TI  - Guidelines for sentinel node biopsy and lymphatic mapping of patients with breast
      cancer.
AB  - OBJECTIVE: To define preliminary guidelines for the use of lymphatic mapping
      techniques in patients with breast cancer. SUMMARY BACKGROUND DATA: Lymphatic
      mapping techniques have the potential of changing the standard of surgical care
      of patients with breast cancer. METHODS: Four hundred sixty-six consecutive
      patients with newly diagnosed breast cancer underwent a prospective trial of
      intraoperative lymphatic mapping using a combination of vital blue dye and
      filtered technetium-labeled sulfur colloid. A sentinel lymph node (SLN) was
      defined as a blue node and/or a hot node with a 10:1 ex vivo gamma probe ratio of
      SLN to non-SLN. All SLNs were bivalved, step-sectioned, and examined with routine
      hematoxylin and eosin (H&E) stains and immunohistochemical stains for
      cytokeratin. A cytokeratin-positive SLN was defined as any SLN with a defined
      cluster of positive-staining cells that could be confirmed histologically on H&E
      sections. RESULTS: Fine-needle aspiration (FNA) or stereotactic core biopsy was
      used to diagnose 195 of the 422 patients (46.2%) with breast cancer; 227 of 422
      patients (53.8%) were diagnosed by excisional biopsy. The SLN was successfully
      identified in 440 of 466 patients (94.4%). Failure to identify an SLN to the
      axilla intraoperatively occurred in 26 of 466 patients (5.6%). In all patients
      who failed lymphatic mappings, a complete axillary dissection was performed, and
      metastatic disease was documented in 4 of 26 (15.4%) of these patients. Of the 26
      patients who failed lymphatic mapping, 11 of 227 (4.8%) were diagnosed by
      excisional biopsy and 15 of 195 (7.7%) were diagnosed by FNA or stereotactic core
      biopsy. Of interest, there was only one skip metastasis (defined as a negative
      SLN with higher nodes in the chain being positive) in a patient with prior
      excisional biopsy. A mean of 1.92 SLNs were harvested per patient. Twenty percent
      of the SLNs removed were positive for metastatic disease in 105 of 440 (23.8%) of
      the patients. Descriptive information on 844 SLNs was evaluated: 339 of 844
      (40.2%) were hot, 272 of 844 (32.2%) were blue, and 233 of 844 (27.6%) were both
      hot and blue. At least one positive SLN was found in 4 of 87 patients (4.6%) with
      noninvasive (ductal carcinoma in situ) tumors. A greater incidence of positive
      SLNs was found in patients who had invasive tumors of increasing size: 18 of 112
      patients (16%) with tumor size between 0.1 mm and 1 cm had positive SLNs.
      However, a significantly greater percentage of patients (43 of 131 [32.8%] with
      tumor size between 1 and 2 cm and 31 of 76 [40.8%] with tumor size between 2 and
      5 cm) had positive SLNs. The highest incidence of positive SLNs was seen with
      patients of tumor size greater than 5 cm; in this group, 9 of 12 (75%) had a
      positive SLN (p < 0.001). CONCLUSIONS: This study demonstrates that accurate SLN
      identification was obtained when all blue and hot lymph nodes were harvested as
      SLNs. Therefore, lymphatic mapping and SLN biopsy is most effective when a
      combination of vital blue dye and radiolabeled sulfur colloid is used.
      Furthermore, these data demonstrate that patients with ductal carcinoma in situ
      or small tumors exhibit a low but significant incidence of metastatic disease to
      the axillary lymph nodes and may benefit most from selective lymphadenectomy,
      avoiding the unnecessary complications of a complete axillary lymph node
      dissection.

PMID- 9605657
TI  - Preoperative terminal ileal and colonic resection histopathology predicts risk of
      pouchitis in patients after ileoanal pull-through procedure.
AB  - OBJECTIVE: This study seeks to compare the histopathology of preoperative
      terminal ileal and colonic resection specimens with pouch biopsies after the
      ileoanal pull-through (IAPT) procedure. SUMMARY BACKGROUND DATA: Pouchitis is the
      most frequent complication of transanal continent reservoirs in patients after
      IAPT. METHODS: The authors conducted 751 consecutive pouch biopsies on 73
      patients with inflammatory bowel disease or familial adenomatous polyposis who
      underwent IAPT by a single surgeon over a 10-year period. In this preliminary
      report, a pathologist, in blinded fashion, has graded 468 of the IAPT pouch
      biopsies and 67 of the patients' preoperative terminal ileal and colonic
      resection histopathology to date. Colonic histopathology was graded by the extent
      and severity of disease, terminal ileal and pouch histopathology by active
      inflammation, chronic inflammation, lymphocyte aggregates, intraepithelial
      lymphocytes, eosinophils, and villous blunting. RESULTS: Extent of colonic
      disease (gross and microscopic) was a significant predictor of active
      inflammation in subsequent IAPT pouch biopsy specimens. Also, the gross extent of
      colonic disease exhibited a significant linear association with pouch
      inflammation. However, the severity of colonic disease was not significantly
      predictive of active inflammation in subsequent IAPT pouch biopsies. Terminal
      ileal active and chronic inflammation were significant predictors of subsequent
      IAPT pouch inflammation. Although lymphocyte aggregates and intraepithelial
      lymphocytes were not predictive, terminal ileum eosinophils and villous blunting
      were significant predictors of active inflammation in subsequent IAPT pouch
      biopsy specimens. CONCLUSIONS: Preoperative terminal ileal and colonic
      histopathology predicts active inflammation of pouches after IAPT. Patients who
      are preoperatively assessed to have extensive disease of the colon, ileal disease
      ("backwash ileitis"), or both appear to be at greater risk for the development of
      pouchitis after IAPT.

PMID- 9605658
TI  - Prospective study of blunt aortic injury: helical CT is diagnostic and
      antihypertensive therapy reduces rupture.
AB  - OBJECTIVE: There were two aims of this study. The first was to evaluate the
      application of helical computed tomography of the thorax (HCTT) for the diagnosis
      of blunt aortic injury (BAI). The second was to evaluate the efficacy of beta
      blockers with or without nitroprusside in preventing aortic rupture. SUMMARY
      BACKGROUND DATA: Aortography has been the standard for diagnosing BAI for the
      past 4 decades. Conventional chest CT has not proven to be of significant value.
      Helical CT scanning is faster and has higher resolution than conventional CT.
      Retrospective studies have suggested the efficacy of antihypertensives in
      preventing aortic rupture. METHODS: A prospective study comparing HCTT to
      aortography in the diagnosis of BAI was performed. A protocol of beta-blockers
      with or without nitroprusside was also examined for efficacy in preventing
      rupture before aortic repair and in allowing delayed repair in patients with
      significant associated injuries. RESULTS: Over a period of 4 years, 494 patients
      were studied. BAI was diagnosed in 71 patients. Sensitivity was 100% for HCTT
      versus 92% for aortography. Specificity was 83% for HCTT versus 99% for
      aortography. Accuracy was 86% for HCTT versus 97% for aortography. Positive
      predictive value was 50% for HCTT versus 97% for aortography. Negative predictive
      value was 100% for HCTT versus 97% for aortography. No patient had spontaneous
      rupture in this study. CONCLUSIONS: HCTT is sensitive for diagnosing intimal
      injuries and pseudoaneurysms. Patients without direct HCTT evidence of BAI
      require no further evaluation. Aortography can be reserved for indeterminate HCTT
      scans. Early diagnosis with HCTT and presumptive treatment with the
      antihypertensive regimen eliminated in-hospital aortic rupture.

PMID- 9605659
TI  - Renal artery repair: consequence of operative failures.
AB  - OBJECTIVE: This report examines the blood pressure and renal function response in
      20 consecutive patients after secondary renal revascularization following failed
      operative repair. SUMMARY BACKGROUND DATA: Most reports describing operative
      failure of renal artery (RA) repair emphasize the technical aspects of redo RA
      reconstruction and the immediate blood-pressure response to secondary operation.
      This report examines the eventual renal function and estimated survival after
      secondary intervention. METHODS: Primary methods of RA reconstruction, primary
      blood pressure and renal function responses, and causes of failed RA repair were
      defined for 20 patients requiring reoperation for recurrent hypertension or renal
      insufficiency. These parameters were compared with secondary procedures and
      eventual blood pressure and renal function response. The eventual outcome for
      these 20 patients was compared with 514 patients managed by primary renal
      revascularization during the same period. RESULTS: Failure of primary RA repair
      correlated with complex fibromuscular dysplasia requiring branch ex vivo
      reconstruction (p = 0.020). RA thrombosis frequently required nephrectomy (83%),
      whereas RA stenosis was successfully reconstructed (91 %; p = 0.001). Primary and
      secondary blood-pressure responses were equivalent (94% vs. 95% cured or
      improved); however, primary and eventual renal function responses differed
      significantly (p = 0.015), with seven patients dialysis-dependent on follow-up.
      Eventual dialysis dependence was associated with preoperative azotemia (p =
      0.022), bilateral failure of primary RA repair (p = 0.007), and an increased risk
      of follow-up death (p = 0.002). Considering all 534 patients, failed RA repair
      demonstrated a significant and independent association with eventual dialysis
      dependence and decreased dialysis-free survival. CONCLUSIONS: Contemporary rates
      of reoperation after surgical RA repair are low. In properly selected patients,
      beneficial blood-pressure response is reliably observed after both primary and
      secondary operative procedures. However, secondary procedures are associated with
      a significant and independent risk of eventual dialysis dependence.

PMID- 9605660
TI  - Impact of a clinical pathway for elective infrarenal aortic reconstructions.
AB  - OBJECTIVE: To determine the impact of a clinical pathway for elective infrarenal
      aortic reconstruction on outcome, resource utilization, and cost in a university
      medical center. SUMMARY BACKGROUND DATA: Clinical pathways have been reported to
      control costs, reduce resource utilization, and maintain or improve the quality
      of patient care, although their use during elective aortic reconstructions
      remains unresolved. METHODS: A clinical pathway was developed for elective
      infrarenal aortic reconstructions by a multidisciplinary group comprised of
      representatives from each involved service. The prepathway practice and costs
      were analyzed and an efficient, cost-effective practice with specific outcome
      measures was defined. The impact of the pathway was determined by retrospective
      comparison of outcome, resource utilization, and cost (total and direct variable)
      between the pathway patients (PATH, n = 45) and a prepathway control group (PRE,
      n = 20). RESULTS: There were no significant differences in the patient
      demographics, comorbid conditions, operative indications, or type of
      reconstruction between the groups. There were no operative deaths and the overall
      complication rate (PRE, 35% vs. PATH, 34%) was similar. The pathway resulted in
      significant decreases in the total length of stay and preoperative length of stay
      and a trend toward a significant decrease (p = 0.08) in the intensive care length
      of stay for the admission during which the operation was performed. The pathway
      also resulted in significant decreases in both direct variable and total hospital
      costs for this admission, as well as a significant decrease in the overall direct
      variable and total hospital costs for the operative admission and the
      preoperative evaluation (< or =30 days before operative admission). Despite these
      reductions, the discharge disposition, 30-day readmissions, and number of
      postoperative clinic visits within 90 days of discharge were not different.
      CONCLUSIONS: Implementation of a clinical pathway for elective infrarenal aortic
      reconstructions dramatically decreased resource utilization and hospital costs
      without affecting the quality of patient care and did not appear to shift the
      costs to another setting.

PMID- 9605661
TI  - Hypothermic circulatory arrest does not increase the risk of ascending thoracic
      aortic aneurysm resection.
AB  - OBJECTIVE: The purpose of this study was to investigate the safety and efficacy
      of a period of deep hypothermic circulatory arrest (DHCA) during elective
      replacement of the ascending thoracic aorta. SUMMARY BACKGROUND DATA: DHCA has
      been implemented in ascending thoracic aortic aneurysm resection whenever the
      anatomy or pathology of the aorta or arch vessels prevents safe or adequate cross
      clamping. Profound hypothermia and retrograde cerebral perfusion have been shown
      to be neurologically protective during ascending aortic replacement under
      circulatory arrest. METHODS: The authors conducted a retrospective analysis of 91
      consecutive patients who underwent repair of chronic ascending thoracic aortic
      aneurysms from 1986 to present. The authors hypothesized that patients undergoing
      DHCA with or without retrograde cerebral perfusion during aneurysm repair were at
      no greater operative risk than patients who received aneurysm resection while on
      standard cardiopulmonary bypass. RESULTS: There were no significant differences
      in hospital mortality, stroke rate, or operative morbidity between patients
      repaired on DHCA when compared to those repaired on cardiopulmonary bypass.
      CONCLUSIONS: DHCA with or without retrograde cerebral perfusion does not result
      in increased morbidity or mortality during the resection of ascending thoracic
      aortic aneurysms. In fact, this technique may prevent damage to the arch vessels
      in select cases and avoid the possible complications associated with cross
      clamping a friable or atherosclerotic aorta.

PMID- 9605662
TI  - Changing patterns in the management of splenic trauma: the impact of nonoperative
      management.
AB  - OBJECTIVE: The recognition that splenectomy renders patients susceptible to
      lifelong risks of septic complications has led to routine attempts at splenic
      conservation after trauma. In 1990, the authors reported that over an 11-year
      study period involving 193 patients, splenorrhaphy was the most common splenic
      salvage method (66% overall) noted, with nonoperative management employed in only
      13% of blunt splenic injuries. This report describes changing patterns of therapy
      in 190 consecutive patients with splenic injuries seen during a subsequent 6-year
      period (1990 to 1996). An algorithmic approach for patient management and
      pitfalls to be avoided to ensure safe nonoperative management are detailed.
      METHODS: Nonoperative management criteria included hemodynamic stability and
      computed tomographic examination without shattered spleen or other injuries
      requiring celiotomy. RESULTS: Of 190 consecutive patients, 102 (54%) were managed
      nonoperatively: 96 (65%) of 147 patients with blunt splenic injuries, which
      included 15 patients with intrinsic splenic pathology, and 6 hemodynamically
      stable patients with isolated stab wounds (24% of all splenic stab wounds). Fifty
      six patients underwent splenectomy (29%) and 32 splenorrhaphy (17%). The mean
      transfusion requirement was 6 units for splenectomy survivors and 0.8 units for
      nonoperative therapy (85% received no transfusions). Fifteen of the 16 major
      infectious complications that occurred followed splenectomy. Two patients failed
      nonoperative therapy (2%) and underwent splenectomy, and one patient required
      splenectomy after partial splenic resection. There no missed enteric injuries in
      patients managed nonoperatively. The overall mortality rate was 5.2%, with no
      deaths following nonoperative management. CONCLUSIONS: Nonoperative management of
      blunt splenic injuries has replaced splenorrhaphy as the most common method of
      splenic conservation. The criteria have been extended to include patients
      previously excluded from this form of therapy. As a result, 65% of all blunt
      splenic injuries and select stab wounds can be managed with minimal transfusions,
      morbidity, or mortality, with a success rate of 98%. Splenectomy, when necessary,
      continues to be associated with excessive transfusion and an inordinately high
      postoperative sepsis rate.

PMID- 9605663
TI  - Trauma service cost: the real story.
AB  - OBJECTIVE: The objective was to define and characterize the costs associated with
      trauma care at a level I trauma center. Once the costs were identified, attending
      physician-led teams were designed to reduce costs within each cost center.
      SUMMARY BACKGROUND DATA: The location and magnitude of the costs on a trauma
      service remain largely unknown. Focused cost-containment strategies remain
      difficult to implement because the expected return on these interventions is
      unknown. METHODS: Cost center data were reviewed for the 40 major DRGs admitted
      for the first 6 months of the fiscal years 1996 and 1997. Data were obtained from
      the hospital finance department using the Transition Systems Inc. accounting
      system. We focused on variable direct costs, those that vary with patient volume
      (e.g., staff nursing expense and medical/surgical supplies). To address issues of
      inflation, pay raises, and changing costs, a proxy value was created for 1996 and
      costs were held constant for the 1997 calculation. The major services that
      constitute cost centers identified in the system were nursing, surgical,
      pharmacy, laboratory, radiology, and emergency services. Attendings were assigned
      to develop and oversee customized cost-reduction modalities specific to each cost
      center. The cost-reduction modalities used to achieve significant savings were as
      follows: nursing, case management approach focusing on early discharge; surgical,
      meeting with operating room (OR) purchasing to modify expensive behavior
      patterns; pharmacy, integrating clinical pharmacist with direct attending
      support; laboratory, enforcing protocol for lab draws; radiology, increasing the
      use of emergency room ultrasound and accepting outside x-rays; and emergency
      services, 24-hour in-house attending staff to reduce emergency room time. The
      surgical and emergency services cost centers predominately generate costs by the
      length of time care is delivered in that area. RESULTS: For each period, data
      from 363 patients were compared. Mean length of stay decreased between the study
      periods from 8.72 to 7.06 days, while the average injury severity score was
      unchanged. Together, these cost centers constituted 87.4% of the total cost of
      care delivered. Significant cost reduction was achieved in all six variable cost
      centers: nursing (24%), surgical (5%), pharmacy (57%), laboratory (27), radiology
      (7%), and emergency (36). The mean cost per case was reduced by 25%. CONCLUSIONS:
      Identification of the true cost centers and directed attending surgeon
      involvement are essential to the development and implementation of a successful
      cost-reduction process.

PMID- 9605664
TI  - Oxygen delivery is an important predictor of outcome in patients with ruptured
      abdominal aortic aneurysms.
AB  - OBJECTIVE: The purpose of this study was to evaluate the relation of oxygen
      delivery (DO2) to the occurrence of multiple organ dysfunction (MOD) in patients
      with ruptured abdominal aortic aneurysms (AAA). SUMMARY BACKGROUND DATA: Patients
      with ruptured AAA are at high risk for the development of MOD and death. Previous
      reports of high-risk general surgical patients have shown improved survival when
      higher levels of DO2 are achieved. METHODS: Hemodynamic data were collected at 4
      hour intervals on 57 consecutive patients (mean age, 70.5 years) who survived 24
      hours after repair of infrarenal ruptured AAA. Patients were resuscitated to
      standard parameters of perfusion (pulse, blood pressure, urine output, normal
      base deficit). MOD was determined based on six organ systems. Standard parametric
      (analysis of variance, t tests) and nonparametric (chi square, Wilcoxon) tests
      were used to compare hemodynamic data, red blood cell requirements, colon
      ischemia, and organ failure for patients with and without MOD. RESULTS: Patients
      who developed MOD had a significantly lower cardiac index and DO2 for the first
      12 hours; the difference was most significant at 8 hours. Logistic regression
      analysis demonstrated that the strongest predictors of MOD were DO2, early onset
      of renal failure, and total number of red blood cells transfused. CONCLUSIONS:
      DO2 is an earlier and better predictor of MOD after ruptured AAA than previously
      identified risk factors. Failure to achieve a normal DO2 in the first 8 hours
      after repair is strongly associated with the development of MOD and a high
      mortality. Strategies to restore normal DO2 may be useful to improve outcome in
      these high-risk patients.

PMID- 9605665
TI  - Collis-Nissen gastroplasty for shortened esophagus: long-term evaluation.
AB  - OBJECTIVE: The authors studied the short- and long-term results of an esophageal
      lengthening procedure (Collis gastroplasty) combined with a Nissen fundoplication
      in the management of patients with shortened esophagus and stricture secondary to
      gastroesophageal reflux disease. Summary Background Data There are several
      options for managing a shortened esophagus. There have been few long-term series
      with analysis of results regarding a lengthening procedure combined with a total
      fundoplication. METHODS: A personal series of 52 patients was examined with
      complete follow-up available for an average of 7 years. RESULTS: There were no
      deaths, esophageal leaks, or esophageal complications in the early postoperative
      period. Control of reflux was excellent and all patients had their dysphagia
      improved. The majority of patients with preoperative strictures required at least
      one postoperative dilation, but in most the need for dilation was short term.
      CONCLUSIONS: The Collis-Nissen procedure is a safe and reasonable alternative in
      the small subset of patients with severe reflux disease causing a shortened
      esophagus and stricture.

PMID- 9605666
TI  - Utility of Gram's stain and efficacy of quantitative cultures for posttraumatic
      pneumonia: a prospective study.
AB  - OBJECTIVE: This prospective trial examined the efficacy of using bronchoalveolar
      lavage (BAL) for the diagnosis of pneumonia (PN) and the utility of Gram's stain
      (GS) for dictating empiric therapy. SUMMARY BACKGROUND DATA: Posttraumatic
      nosocomial PN remains a significant cause of morbidity and mortality. However,
      its diagnosis is elusive, especially in multiply injured patients. The systemic
      inflammatory response syndrome of fever, leukocytosis, and a hyperdynamic state
      is common in trauma patients, especially patients with pulmonary contusion.
      Bronchoscopy with BAL with quantitative cultures of the lavage effluent may
      distinguish between PN and systemic inflammatory response syndrome, and GS of the
      lavage effluent may guide empiric therapy before quantitative culture results.
      METHODS: Mechanically ventilated trauma patients with a clinical diagnosis of PN
      (fever, leukocytosis, purulent sputum, and new or changing infiltrate on chest
      radiograph) underwent bronchoscopy with BAL. Effluent was sent for GS and
      quantitative cultures. The diagnostic threshold for PN was > or =10(5) colony
      forming units (CFU)/mL, and antibiotics were continued. Antibiotics were stopped
      for < 10(5) CFU/mL and the diagnosis of systemic inflammatory response syndrome
      was made. Causative organisms for PN were compared to GS. RESULTS: Over a 2-year
      period, 232 patients underwent 443 bronchoscopies with BAL (71% men, 29% women;
      mean age, 41). The mean injury severity score was 30. Sixty percent of the
      patients had pulmonary contusion, and 59% were cigarette smokers. The overall
      incidence of PN was 39% and was no different regardless of the number of BALs a
      patient had. The false-negative rate of BAL was 7%. GS identified gram-positive
      organisms in 80% of patients with gram-positive PN and 40% of patients with gram
      negative PN. GS identified gram-negative organisms in 52% of patients with gram
      positive PN and 77% with gram-negative PN. The duration of the intensive care
      unit stay relative to the timing of BAL was beneficial for guiding empiric
      therapy. BAL in week 1 primarily identified Haemophilus influenzae and gram
      positive organisms; Acinetobacter sp. and Pseudomonas sp. were more common after
      week 1. CONCLUSIONS: Bronchoscopy with BAL is an effective method to diagnose PN
      and avoids prolonged, unnecessary antibiotic therapy. Empiric therapy should be
      adjusted to the duration of the intensive care unit stay because the causative
      bacteria flora changes over time. GS of BAL effluent correlates poorly with
      quantitative cultures and is not reliable for dictating empiric therapy.

PMID- 9605667
TI  - Clinical outcome in stage I to III breast carcinoma and eIF4E overexpression.
AB  - OBJECTIVE: The objective of this study is to determine if high eukaryotic
      initiation factor 4E (eIF4E) overexpression (sevenfold elevation or more over
      benign breast tissue) is associated with a worse clinical outcome. SUMMARY
      BACKGROUND DATA: Dysregulation of cellular functions by selective overexpression
      of specific proteins can lead to malignant transformation. The overexpression of
      eIF4E preferentially increases translation of mRNAs with long, G-C rich 5'
      untranslated regions. Selective gene products, such as tumor neoangiogenic
      factors, ornithine decarboxylase, and cyclin D1, are upregulated. METHODS: One
      hundred fourteen breast specimens were analyzed and eIF4E overexpression was
      quantified by Western blot analysis. Quantification for eIF4E protein level was
      accomplished using a rabbit anti-eIF4E antibody and colorimetric development of
      Western blots using nitro blue tetrazolium and 5-bromo-4-chloro-3-indolyl
      phosphate. The blots were scanned and analyzed by densitometry. Treatment,
      pathologic, and clinical outcome data variables were analyzed. Statistical
      analysis was performed to determine if eIF4E overexpression is associated with
      breast cancer clinical outcome. RESULTS: In the 55 benign specimens, the mean
      eIF4E expression was 1.1+/-0.4 fold (mean +/- standard deviation). All 59
      malignant breast carcinoma specimens were noted to have eIF4E overexpression
      (range, 1.9-fold to 30.6-fold), with a mean overexpression of 10.8+/-6.3-fold.
      The mean level of eIF4E expression in malignant specimens was higher than benign
      specimens (p < 0.05, unpaired t test). The degree of eIF4E overexpression appears
      to be independent of T and N stage. In the 21 patients with eIF4E overexpression
      of less than sevenfold, there was one cancer recurrence but no cancer-related
      deaths. In the 38 patients with high eIF4E overexpression (sevenfold or more), 14
      patients had breast cancer recurrences (p = 0.03, log rank test), of whom 11 have
      died from the disease (p = 0.04, log rank test). The average follow-up interval
      in this study was 40 months. CONCLUSIONS: Patients with stage I to III breast
      cancer and high eIF4E overexpression had a higher rate of cancer recurrence and a
      higher rate of cancer-related death when compared to similar-stage breast cancer
      patients with low eIF4E overexpression. Therefore, eIF4E protein overexpression
      may be of prognostic value in stage I to III breast carcinoma.

PMID- 9605668
TI  - Effectiveness of positron emission tomography for the detection of melanoma
      metastases.
AB  - OBJECTIVE: The purpose of this study was to determine the sensitivity,
      specificity, and clinical utility of 18F 2-fluoro-2-deoxy-D-glucose (FDG) total
      body positron emission tomography (PET) scanning for the detection of metastases
      in patients with malignant melanoma. SUMMARY BACKGROUND DATA: Recent preliminary
      reports suggest that PET using FDG may be more sensitive and specific for
      detection of metastatic melanoma than standard radiologic imaging studies using
      computed tomography (CT). PET technology is showing utility in the detection of
      metastatic tumors from multiple primary sites including breast, lung, lymphoma,
      and melanoma. However, little information is available concerning the general
      utility, sensitivity, and specificity of PET scanning of patients with metastatic
      melanoma. METHODS: One hundred three PET scans done on 76 nonrandomized patients
      having AJCC stage II to IV melanoma were prospectively evaluated. Patients were
      derived from two groups. Group 1 (63 patients) had PET, CT (chest and abdomen),
      and magnetic resonance imaging (MRI; brain) scans as a part of staging
      requirements for immunotherapy protocols. Group 2 (13 nonprotocol patients) had
      PET, CT, and MRI scans as in group 1, but for clinical evaluation only. PET scans
      were done using 12 to 20 mCi of FDG given intravenously. Results of PET scans
      were compared to CT scans and biopsy or cytology results. RESULTS: PET scanning
      for the detection of melanoma metastases had a sensitivity of 94.2% and a
      specificity of 83.3% compared to 55.3% and 84.4%, respectively, for CT scanning.
      Factors that produced false-positive PET scans were papillary carcinoma of the
      thyroid (1), bronchogenic carcinoma (1), inflamed epidermal cyst (1), Warthin's
      tumor of the parotid gland (1), surgical wound inflammation (2), leiomyoma of the
      uterus (1), suture granuloma (1), and endometriosis (1). The four false-negative
      scans were thought to be due to smaller (<0.3 to 0.5 cm) and diffuse areas of
      melanoma without a mass effect. CONCLUSIONS: PET scanning is extremely sensitive
      (94.2%) and very specific (83.3%) for identifying metastatic melanoma,
      particularly in soft tissues, lymph nodes, and the liver. A number of second
      primary or metastatic tumors and an inflammatory response can also be localized
      by PET. This observation mandates a close clinical correlation with positive PET
      and emphasizes the importance of establishing a tissue diagnosis. False-negative
      scans in the presence of metastases are rare (4% of scans). Metastases < or =5 mm
      in diameter may not image well. PET is superior to CT in detecting melanoma
      metastases and has a role as a primary strategy in the staging of melanoma.

PMID- 9605669
TI  - Effect of glutamine on methotrexate efficacy and toxicity.
AB  - OBJECTIVE: To examine the effect of oral glutamine (GLN) on the efficacy and
      toxicity of methotrexate (MTX). SUMMARY BACKGROUND DATA: The use of high-dose
      chemotherapy regimens is limited by the severity of their toxicities. Oral GLN
      has been shown to decrease the gut toxicity seen with MTX treatment while
      enhancing its tumoricidal effect. METHODS AND RESULTS: Studies were done in
      laboratory rats and in breast cancer outpatients. Fischer 344 rats were
      randomized to 48 hours of prefeeding with GLN (1 g/kg/day) or an isonitrogenous
      amount of glycine. Rats were killed 24 hours after receiving a 20-mg/kg
      intraperitoneal dose of MTX. In the GLN group, there was a threefold increase in
      total MTX in the tumor as compared with the control group, and this increase was
      in both the diglutamated and pentaglutamated MTX. Inversely, there was a
      significant decrease in the total polyglutamated MTX in the gut in the GLN group.
      Given the results of this preclinical study, the authors performed a phase I
      trial. Nine patients diagnosed with inflammatory breast cancer received GLN (0.5
      g/kg/day) during MTX neoadjuvant therapy, escalating from doses of 40 mg/m2 to
      100 mg/m2 weekly for 3 weeks, followed by a doxorubicin-based regimen. No
      toxicity of oral GLN was detected. No patient showed any sign of chemotherapy
      related toxicity. One patient had a grade I mucositis. Except for one, all
      patients responded to the chemotherapy regimen. Median survival was 35 months.
      CONCLUSIONS: These studies suggest that GLN supplementation is safe in its
      administration to the tumor-bearing host receiving MTX. By preferentially
      increasing tumor retention of MTX over that of normal host tissue, GLN may serve
      to increase the therapeutic window of this chemotherapeutic age.

PMID- 9605670
TI  - Adverse anesthesia events in children exposed to environmental tobacco smoke:
      exposure to environmental tobacco smoke and the risk of adverse respiratory
      events in children receiving general anesthesia.

PMID- 9605671
TI  - How does mu-opioid receptor blockade work in addicted patients?

PMID- 9605672
TI  - Exposure to environmental tobacco smoke and the risk of adverse respiratory
      events in children receiving general anesthesia.
AB  - BACKGROUND: Exposure to environmental tobacco smoke is associated with
      detrimental effects on pulmonary function in children. The authors investigated
      the relation between airway complications in children receiving general
      anesthesia and the passive inhalation of tobacco smoke. METHODS: Six hundred two
      children scheduled to receive general anesthesia were enrolled in this
      prospective study. The anesthesiologist and the recovery room nurse, unaware of
      the smoke exposure history, recorded the occurrence of airway complications. A
      history of passive smoking was assessed by measuring the urinary concentration of
      the major nicotine metabolite cotinine and by questionnaire. RESULTS: Airway
      complications occurred in 42% of the patients with urinary concentrations of
      cotinine > or =40 ng/ml, in 33% of the patients with concentrations of cotinine
      between 10.0 and 39.9 ng/ml, and in 24% of the patients with concentrations of
      cotinine < 10 ng/ml (P = 0.01 for the trend among the three groups). The gender
      of the child (P = 0.001) and the educational level of the child's mother (P =
      0.0008) significantly modified the effect of the concentration of cotinine on the
      incidence of adverse respiratory events. CONCLUSIONS: There is a strong
      association between passive inhalation of tobacco smoke and airway complications
      in children receiving general anesthesia. The relationship is greatest for girls
      and for those whose mothers have a lower level of education. Passive smoking
      should be regarded as a risk factor in children undergoing general anesthesia.

PMID- 9605673
TI  - Profound increase in epinephrine concentration in plasma and cardiovascular
      stimulation after mu-opioid receptor blockade in opioid-addicted patients during
      barbiturate-induced anesthesia for acute detoxification.
AB  - BACKGROUND: Acute displacement of opioids from their receptors by administration
      of large doses of opioid antagonists during general anesthesia is a new approach
      for detoxification of patients addicted to opioids. The authors tested the
      hypothesis that mu-opioid receptor blockade by naloxone induces cardiovascular
      stimulation mediated by the sympathoadrenal system. METHODS: Heart rate, cardiac
      index, and intravascular pressures were measured in 10 patients addicted to
      opioids (drug history; mean +/- SD, 71 +/- 51 months) during a program of
      methadone substitution (96 +/- 57 mg/day). Cardiovascular variables and
      concentrations of catecholamine in plasma were measured in the awake state,
      during methohexital-induced anesthesia (dose, 74 +/- 44 microg x kg(-1) x min(
      1)) before administration of naloxone, and repeatedly during the first 3 h of mu
      opioid receptor blockade. Naloxone was administered initially in an intravenous
      dose of 0.4 mg, followed by incremental bolus doses (0.8, 1.6, 3.2, and 6.4 mg)
      at 15-min intervals until a total dose of 12.4 mg had been administered within 60
      min; administration was then continued by infusion (0.8 mg/h). RESULTS:
      Concentration of epinephrine in plasma increased 30-fold (15 +/- 9 to 458 +/- 304
      pg/ml), whereas concentration of norepinephrine in plasma only increased to a
      minor extent (76 +/- 44 to 226 +/- 58 pg/ml, P < 0.05). Cardiac index increased
      by 74% (2.7 +/- 0.41 to 4.7 +/- 1.7 min(-1) x m(-2)), because of increases in
      heart rate (89 +/- 16 to 108 +/- 17 beats/min) and stroke volume (+44%), reaching
      maximum 45 min after the initial injection of naloxone. In parallel, systemic
      vascular resistance index decreased (-40%). Systolic arterial pressure
      significantly increased (113 +/- 16 to 138 +/- 16 mmHg), whereas diastolic
      arterial pressure did not change. CONCLUSIONS: Despite barbiturate-induced
      anesthesia, acute mu-opioid receptor blockade in patients addicted to opioids
      induces profound epinephrine release and cardiovascular stimulation. These data
      suggest that long-term opioid receptor stimulation changes sympathoadrenal and
      cardiovascular function, which is acutely unmasked by mu-opioid receptor
      blockade. Because of the attendant cardiovascular stimulation, acute
      detoxification using naloxone should be performed by trained anesthesiologists or
      intensivists.

PMID- 9605674
TI  - Desflurane reduces the febrile response to administration of interleukin-2.
AB  - BACKGROUND: Intraoperative fever is relatively rare considering how often
      pyrogenic causes are likely to be present and how common fever is
      postoperatively. This low incidence suggests that general anesthesia per se
      inhibits the normal response to pyrogenic stimulation. The authors therefore
      tested the hypothesis that desflurane-induced anesthesia produces a dose
      dependent inhibition of the febrile response. METHODS: Eight volunteers were
      studied, each on 3 study days. Each was given an intravenous injection of 50,000
      IU/ kg of interleukin-2 (elapsed time, 0 h), followed 2 h later by 100,000 IU/kg.
      One hour after the second dose, the volunteers were assigned randomly to three
      doses of desflurane to induce anesthesia: (1) 0.0 minimum alveolar concentration
      (MAC; control), (2) 0.6 MAC, and (3) 1.0 MAC. Anesthesia continued for 5 h. Core
      temperatures were recorded from the tympanic membrane. Thermoregulatory
      vasoconstriction was evaluated using forearm-minus-fingertip skin temperature
      gradients; shivering was evaluated with electromyography. Integrated and peak
      temperatures during anesthesia were compared with repeated-measures analysis of
      variance and Scheffe's F tests. RESULTS: Values are presented as mean +/- SD.
      Desflurane reduced the integrated (area under the curve) febrile response to
      pyrogen, from 7.7 +/- 2.0 degrees C x h on the control day to 2.1 +/- 2.3 degrees
      C x h during 0.6 MAC and to -1.4 +/- 3.1 degrees C x h during 1.0 MAC desflurane
      induced anesthesia. Peak core temperature (elapsed time, 5-8 h) decreased in a
      dose-dependent fashion: 38.6 +/- 0.5 degrees C on the control day, 37.7 +/- 0.7
      degrees C during 0.6 MAC and 37.2 +/- 1.0 degrees C during 1.0 MAC desflurane
      anesthesia. Rising core temperature was always associated with fingertip
      vasoconstriction and often with shivering. CONCLUSIONS: Desflurane-induced
      anesthesia produced a dose-dependent decrease in integrated and peak core
      temperatures after administration of pyrogen, with 1.0 MAC essentially
      obliterating fever. Anesthetic-induced inhibition of the pyrogenic response is
      therefore one reason that fever is an inconsistent clinical response to
      inflammation during surgery.

PMID- 9605675
TI  - The influence of method of administration and covariates on the pharmacokinetics
      of propofol in adult volunteers.
AB  - BACKGROUND: Unresolved issues with propofol include whether the pharmacokinetics
      are linear with dose, are influenced by method of administration (bolus vs.
      infusion), or are influenced by age. Recently, a new formulation of propofol
      emulsion, containing disodium edetate (EDTA), was introduced in the United
      States. Addition of EDTA was found by the manufacturer to significantly reduce
      bacterial growth. This study investigated the influences of method of
      administration, infusion rate, patient covariates, and EDTA on the
      pharmacokinetics of propofol. METHODS: Twenty-four healthy volunteers aged 26-81
      yr were given a bolus dose of propofol, followed 1 h later by a 60-min infusion.
      Each volunteer was randomly assigned to an infusion rate of 25, 50, 100, or 200
      microg x kg(-1) x min(-1). Each volunteer was studied twice under otherwise
      identical circumstances: once receiving propofol without EDTA and once receiving
      propofol with EDTA. The influence of the method of administration and of the
      volunteer covariates was explored by fitting a three-compartment mamillary model
      to the data. The influence of EDTA was investigated by direct comparison of the
      measured concentrations in both sessions. RESULTS: The concentrations of propofol
      with and without EDTA were not significantly different. The concentration
      measurements after the bolus dose were significantly underpredicted by the
      parameters obtained just from the infusion data. The kinetics of propofol were
      linear within the infusion range of 25-200 microg x kg(-1) x min(-1). Age was a
      significant covariate for Volume2 and Clearance2, as were weight, height, and
      lean body mass for the metabolic clearance. CONCLUSIONS: These results
      demonstrate that method of administration (bolus vs. infusion), but not EDTA,
      influences the pharmacokinetics of propofol. Within the clinically relevant
      range, the kinetics of propofol during infusions are linear regarding infusion
      rate.

PMID- 9605676
TI  - A bronchoscopic, computer-assisted examination of the changes in dimension of the
      infant tracheal lumen with changes in head position: implications for emergency
      airway management.
AB  - BACKGROUND: Resuscitation guidelines caution against extreme extension or flexion
      of an infant's head because tracheal obstruction may occur. No data support this
      recommendation. The authors therefore examined the dimensions of the tracheal
      lumen in neutral, extended, and flexed head positions in infants undergoing
      general endotracheal anesthesia for elective surgery. METHODS: Eighteen healthy
      full-term infants were studied. A flexible fiberoptic bronchoscope was passed
      through a previously inserted endotracheal tube and positioned above the cricoid
      cartilage. Video recordings were taken in each of three head positions.
      Recordings were analyzed by an investigator blinded to head position. A computer
      digitized technique was used to measure anterior-posterior and lateral dimensions
      and cross-sectional area. Data were analyzed using paired t tests and sign tests.
      RESULTS: No significant differences in mean tracheal dimensions with changes in
      head position were found. No infant had complete tracheal obstruction. Infants
      were equally as likely to have a small increase as they were to have a small
      decrease in tracheal dimension with changes in head position. CONCLUSIONS:
      Despite the belief that infants and neonates have obstruction at the level of the
      trachea with extreme positions of the head, the authors were unable to
      demonstrate this phenomenon.

PMID- 9605677
TI  - Comparison of the effect of etomidate and desflurane on brain tissue gases and pH
      during prolonged middle cerebral artery occlusion.
AB  - BACKGROUND: The authors compared the effects of etomidate and desflurane on brain
      tissue oxygen pressure (PO2), carbon dioxide pressure (PCO2), and pH in patients
      who had middle cerebral artery occlusion for > 15 min. METHODS: After a
      craniotomy, a probe that measures PO2, PCO2, and pH was inserted into cortical
      tissue at risk for ischemia during middle cerebral artery occlusion. A burst
      suppression pattern of the electroencephalogram was induced with etomidate (n =
      6) or 9% end-tidal desflurane (n = 6) started before middle cerebral artery
      occlusion. Mean blood pressure was supported with phenylephrine to 90-95 mmHg.
      RESULTS: During baseline conditions, tissue PO2, PCO2, and pH were similar
      between the two groups (PO2 = 15 mmHg, PCO2 = 60 mmHg, pH = 7.1). During
      administration of etomidate before middle cerebral artery occlusion, tissue PO2
      decreased in five of six patients without a change in PCO2 or pH. During
      administration of 9% desflurane, tissue PO2 and pH increased before middle
      cerebral artery clipping. Middle cerebral artery occlusion for an average of 33
      min with etomidate and 37 min with desflurane produced a decrease in pH with
      etomidate (7.09 to 6.63, P < 0.05) but not with desflurane (7.12 to 7.15).
      CONCLUSION: These results suggest that tissue hypoxia and acidosis are often
      observed during etomidate treatment and middle cerebral artery occlusion.
      Treatment with desflurane significantly increases tissue PO2 alone and attenuates
      acidotic changes to prolonged middle cerebral artery occlusion.

PMID- 9605678
TI  - Pulsed Doppler ultrasonography guidance for catheterization of the subclavian
      vein: a randomized study.
AB  - BACKGROUND: Catheterization of the subclavian vein may lead to severe
      complications. The current randomized study compared a technique of pulsed
      Doppler ultrasonography guidance and the standard method for subclavian vein
      catheterization. METHODS: Standard and Doppler ultrasonography guidance methods
      were performed by the same physician in 286 patients, 143 in each group. Primary
      end points were immediate complications (arterial puncture, pneumothorax, wrong
      position of catheter tip), failures, the number of subclavian vein
      catheterizations with immediate complication or failure, the number of skin
      punctures per catheterization, and the time to placement of the guide wire. The
      secondary end points were the determination of predicting factors of successful
      cannulation in each group. RESULTS: Both groups were similar according to
      morphologic parameters of the patients. A greater number of subclavian vein
      catheterizations were performed on the right side using Doppler guidance (105 vs.
      73, P < 0.01). Doppler guidance decreased complications (5.6% vs. 16.8%, P <
      0.01), largely because of a smaller number of catheters for which the tip was
      defined to be in incorrect position (0.7% vs. 7.7%, P < 0.01). The time to
      catheterization was longer with Doppler guidance (300 vs. 27 s, P < 0.001).
      Failures, catheterizations of the subclavian vein with immediate complications or
      failure, and the total number of skin punctures per catheterization were similar
      in both groups. Using Doppler guidance, the presence of a good Doppler signal
      (124 of 143) was predictive of successful catheterization (123 successful
      cannulations, P < 0.001). CONCLUSIONS: Doppler guidance reduces the incidence of
      inappropriately positioned subclavian catheters.

PMID- 9605679
TI  - Effects of ketamine on the contractility of failing and nonfailing human heart
      muscles in vitro.
AB  - BACKGROUND: Induction of anesthesia with ketamine may decrease cardiac output in
      critically ill patients. The direct effects of ketamine on the failing human
      myocardium are unknown. This study examined the effects of ketamine on
      contractility of human failing and nonfailing myocardium in vitro. METHODS:
      Trabecular muscles were obtained from the left ventricles and right atria of 10
      patients with heart failure undergoing transplantation and from the right atria
      of 14 patients undergoing coronary artery bypass surgery. Muscles were dissected
      and mounted in a 37 degrees C bath and stimulated at 1 Hz. Isometric contraction
      variables were recorded before and after addition of ketamine (concentrations
      between 0.44 and 440.0 microM) to the bath. The effects of ketamine were compared
      with those of buffer. To test muscle contractility, at the end of each
      experiment, 1 microM isoproterenol was added. RESULTS: Ketamine caused a
      significant dose-dependent decrease in developed tension in nonfailing atrial and
      failing atrial and ventricular muscles (P < 0.01 for all). In vehicle-treated
      muscles, developed tension remained stable, and isoproterenol increased developed
      tension 136% (nonfailing atrial muscles) and 178% (failing atrial and ventricular
      muscles; P < 0.01). In nonfailing atrial muscle, isoproterenol restored the
      ketamine-induced decrease in developed tension toward the baseline value. In
      failing atrial and ventricular muscles exposed to ketamine, isoproterenol did not
      counteract the ketamine. CONCLUSIONS: Ketamine exerts a direct dose-dependent
      negative inotropic effect in human heart muscles. The failing myocardium exposed
      to ketamine has reduced ability to increase contractility even in the presence of
      increased beta-adrenergic stimulation.

PMID- 9605680
TI  - Metabolic changes during recovery in normothermic versus hypothermic patients
      undergoing surgery and receiving general anesthesia and epidural local anesthetic
      agents.
AB  - BACKGROUND: Mild hypothermia is accompanied by metabolic changes. Epidural local
      anesthetic agents attenuate the surgical stress response, but it is not known
      whether they modulate thermal stress. METHODS: Thirty patients undergoing
      colorectal surgery, performed by one surgical team, received epidural 0.5%
      bupivacaine to achieve T3-S5 sensory block. They were then assigned randomly to
      two groups of 15 patients each. The control or unwarmed group was left to cool
      during surgery, whereas active warming was used in the warmed group. General
      anesthesia was induced by thiopentone, vecuronium, fentanyl, nitrous oxide in
      oxygen, and enflurane. At the end of surgery, both groups received epidural 0.25%
      bupivacaine to maintain a T5-L3 sensory block. Aural canal (core) and skin
      surface (15 sites) temperatures; oxygen consumption; pain visual analogue score;
      and concentrations of epinephrine, norepinephrine, glucose, cortisol, lactate,
      and free fatty acids in plasma were measured before epidural blockade, 30 min
      after epidural blockade, at the end of surgery, and for 4 h after surgery.
      Patients and those measuring the outcomes were unaware of group allocation.
      RESULTS: Core and mean skin temperatures decreased significantly in the control
      group (P < 0.001) but not in the warmed group. Catecholamine concentrations in
      plasma decreased significantly after epidural block, and although concentration
      of epinephrine in plasma increased from baseline sharply in the control group at
      the end of surgery (P = 0.004), it decreased in the warmed group (P = 0.007).
      During recovery, there was no difference between the two groups for
      norepinephrine concentrations in plasma, body weight-adjusted oxygen consumption,
      pain visual analogue score, and metabolites. CONCLUSIONS: The postoperative
      metabolic changes obtained with epidural block were similar except for an
      attenuated concentration of epinephrine in normothermic patients compared with
      those who were mildly hypothermic.

PMID- 9605681
TI  - The glottic aperture seal airway: a new ventilatory device.
AB  - BACKGROUND: None of the presently used airway devices are ideal regarding ease of
      insertion, alignment with the laryngeal inlet, and provision of a high-pressure
      seal from the environment. The purpose of this study was to determine, in awake
      volunteers, the performance of a new ventilatory device, the glottic aperture
      seal airway, regarding ease of insertion, alignment with the laryngeal inlet, and
      forced exhalation seal pressure (PFES). METHODS: The glottic aperture seal airway
      consists of a curved tubular component that ends in the middle of an elliptical
      foam cushion glottic component. The posterior surface of the foam has a curved
      flexible plastic backing, which imparts a 60 degree angle between the proximal
      half and the distal half of the foam cushion. When the glottic aperture seal
      airway is properly in situ in a supine patient, the proximal half of the foam
      cushion is opposite the laryngeal inlet. The posterior surface of the plastic
      backing has a balloon attached to it. Inflation of the balloon presses the
      ventilation hole and foam cushion up against the laryngeal inlet, thereby
      creating a seal from the environment. Using the laryngeal mask airway as a
      control device, the glottic aperture seal airway was tested for time and ease of
      insertion, fiberoptic alignment with the laryngeal inlet, and PFES in 18 lightly
      sedated and locally anesthetized volunteers. RESULTS: The glottic aperture seal
      and laryngeal mask airways were inserted with equal ease and speed. The
      fiberoptic alignment with the larynx was excellent for both the glottic aperture
      seal and laryngeal mask airways. In all volunteers, the mean +/- SD PFES values
      at 0-, 10-, 20-, 30-, and 40-ml balloon inflation volumes of the glottic aperture
      seal airway were 23.4 +/- 11.8, 29.6 +/- 12.4, 42.7 +/- 12.5, 56.9 +/- 5.6, and
      60 +/- 0 cm H2O, respectively; the PFES at > or = 20 ml balloon inflation volume
      of the glottic aperture seal airway was significantly greater than with the
      laryngeal mask airway (19.4 +/- 6.7 cm H2O, P < 0.01). A PFES of > or =60 cm H2O
      was achieved with the glottic aperture seal airway in all volunteers (n = 2 at 10
      ml, n = 3 at 20 ml, n = 9 at 30 ml, and n = 4 at 40 ml). The glottic aperture
      seal airway did not cause any trauma. CONCLUSION: In awake volunteers, the
      glottic aperture seal and laryngeal mask airways were equally easy to insert and
      position. The glottic aperture seal airway was capable of achieving a higher PFES
      than the laryngeal mask airway.

PMID- 9605682
TI  - Desflurane-mediated sympathetic activation occurs in humans despite preventing
      hypotension and baroreceptor unloading.
AB  - BACKGROUND: Increasing concentrations of desflurane result in progressive
      decreases in blood pressure (BP) and, unlike other currently marketed, potent
      volatile anesthetics, heightened sympathetic nervous system activity. This study
      aimed to determine whether baroreflex mechanisms are involved in desflurane
      mediated sympathetic excitation. METHODS: Healthy volunteers were anesthetized
      with desflurane (n = 8) or isoflurane (n = 9). Heart rate (HR; measured by
      electrocardiograph), blood pressure (BP; measured by arterial catheter), and
      efferent sympathetic nerve activity (SNA; obtained from percutaneous recordings
      from the peroneal nerve) were monitored. Baroreflex sensitivity was evaluated at
      baseline while volunteers were conscious and during 0.5, 1, and 1.5 minimum
      alveolar concentration (MAC) anesthesia via bolus injections of nitroprusside
      (100 microg) and phenylephrine (150 microg) to decrease and increase BP. To
      prevent the BP decline with increasing depths of anesthesia, phenylephrine was
      infused to maintain mean BP at the 0.5 MAC level. RESULTS: The HR, BP, and SNA
      were similar between the groups at the conscious baseline measurement. Efferent
      SNA did not change during higher MAC of isoflurane, but it increased
      progressively as desflurane concentrations were increased beyond 0.5 MAC, despite
      maintaining BP at the 0.5 MAC value with phenylephrine infusions (P < 0.05).
      Cardiac baroslopes (based on changes in HR) were progressively and similarly
      decreased with increasing concentrations of isoflurane and desflurane (P < 0.05).
      Sympathetic baroslopes (based on SNA) decreased with increasing isoflurane
      concentrations but were maintained with increasing concentrations of desflurane;
      the response was significantly different between groups. CONCLUSIONS: The
      increase in basal levels of SNA with increasing concentrations of desflurane
      persisted despite "fixing" BP and thus is probably not due to hypotension and
      unloading of the baroreceptors. Further, the preservation of reflex increases in
      SNA to nitroprusside during desflurane indicates that desflurane preserves one
      component of the baroreflex in humans when BP is "fixed."

PMID- 9605683
TI  - Dobutamine stress echocardiography to detect inducible demand ischemia in
      anesthetized patients with coronary artery disease.
AB  - BACKGROUND: A cardiac risk stratification test that can be performed during
      operation would be expected to give valuable information for the therapeutic
      management of patients who need urgent noncardiac surgery. This study was
      designed to evaluate the feasibility and safety of a dobutamine-atropine stress
      protocol to detect inducible demand ischemia in anesthetized patients. METHODS: A
      standard dobutamine-atropine stress protocol was performed in 80 patients with
      severe coronary artery disease during fentanyl-isoflurane anesthesia. Biplane
      transesophageal echocardiography and 12-lead electrocardiography were used to
      detect induced ischemia. After dobutamine testing, esmolol, nitroglycerin, or
      both were used to revert ischemia and any hemodynamic changes, as appropriate.
      RESULTS: The protocol detected inducible ischemia or achieved the target heart
      rate in 75 of the 80 (94%) patients. None of the prospectively defined adverse
      outcomes, such as cardiovascular collapse, severe ventricular arrhythmia,
      persistent (> or =5 min) ischemia, or hemodynamic instability, occurred in any of
      the patients. Ischemia was induced and detected in 73 of the 80 (91%) patients.
      CONCLUSION: Dobutamine stress echocardiography is feasible in anesthetized
      patients with severe coronary artery disease. The lack of serious complications
      and the high sensitivity to detect inducible ischemia in this patient population
      provide the basis for further evaluation of the safety and diagnostic value of
      dobutamine stress echocardiography during general anesthesia in larger studies of
      patients at risk for coronary artery disease undergoing noncardiac surgery.

PMID- 9605684
TI  - Nitric oxide synthase inhibitors alter ventilation in isoflurane anesthetized
      rats.
AB  - BACKGROUND: Nitric oxide (NO) is present in medullary structures and can modulate
      respiratory rhythm. The authors determined if spontaneous ventilation at rest and
      in response to increased carbon dioxide is altered by selective neuronal NO
      synthase (NOS; 7-nitro-indazole, 7-NI) or nonselective (neuronal plus
      endothelial) NOS (NG-L-arginine methyl ester [L-NAME] and NG-monomethyl L
      arginine [L-NMMA]) inhibitors in rats anesthetized with isoflurane. METHODS:
      Fifty-four rats received either L-NAME or L-NMMA (1, 10, and 30 mg/kg) or 7-NI
      (20, 80, and 400 mg/kg) and were compared with time controls (isoflurane = 1.4%),
      with isoflurane concentrations (1.6%, 1.8%, and 2%) increased consistent with the
      increased anesthetic depth caused by NOS inhibitors, or with L-arginine (300
      mg/kg). Tidal volume (VT), respiratory frequency (f), minute ventilation (VE),
      and ventilatory responses to increasing carbon dioxide were determined. RESULTS:
      L-NAME and L-NMMA decreased resting VT and VE, whereas 7-NI had no effect.
      Increasing concentrations of isoflurane decreased resting f, VT, and VE. L-NAME
      and L-NMMA decreased VT and VE, whereas 7-NI had no effect at 8%, 9%, and 10% end
      tidal carbon dioxide (ETCO2). Increasing concentrations of isoflurane decreased
      f, VT, and VE at 8%, 9%, and 10% ETCO2. The slope of VE versus ETCO2 was
      decreased by isoflurane but was unaffected by L-NAME, L-NMMA, or 7-NI. L-arginine
      alone had no effect on ventilation. CONCLUSIONS: Nonselective NOS inhibitors
      decreased VT and VE at rest and at increased carbon dioxide levels but did not
      alter the slope of the carbon dioxide response. Selective neuronal NOS inhibition
      had no effect, suggesting that endothelial NOS may be the isoform responsible for
      altering ventilation. Finally, the cause of the decreased ventilation is not a
      result of the enhanced anesthetic depth caused by NOS inhibitors.

PMID- 9605685
TI  - Interaction of isoflurane and sevoflurane with alpha- and beta-adrenoceptor
      stimulations in rat myocardium.
AB  - BACKGROUND: Halothane potentiates the positive inotropic effects of alpha- and
      beta-adrenoceptor stimulations but impairs the positive lusitropic effect of beta
      adrenoceptor stimulations. However, the interactions of isoflurane and
      sevoflurane with alpha- and beta-adrenoceptor stimulation have not been entirely
      defined. METHODS: The effects of 1 minimum alveolar concentration isoflurane and
      sevoflurane on the inotropic responses induced by phenylephrine (10(-8) to 10(-4)
      M) or isoproterenol (10(-8 to 10(-4) M) were studied in rat left ventricular
      papillary muscles in vitro (Krebs-Henseleit solution, 29 degrees C; pH, 7.4; 0.5
      mM calcium; stimulation frequency, 12 pulses/min). The positive lusitropic
      effects of alpha- and beta-adrenoceptor stimulations were studied under isotonic
      and isometric conditions. Data are mean percentages of baseline +/- SEM. RESULTS:
      In control groups, phenylephrine (134 +/- 8%; P < 0.05) and isoproterenol (171 +/
      7%; P < 0.05) induced a positive inotropic effect. Isoflurane enhanced the
      positive inotropic effects of phenylephrine (185 +/- 10%; P < 0.05) and of
      isoproterenol (203 +/- 11%; P < 0.05). Sevoflurane enhanced the positive
      inotropic effects of phenylephrine (187 +/- 10%; P < 0.05) and of isoproterenol
      (228 +/- 11%; P < 0.05). These potentiations were similar to those previously
      reported with halothane. Isoflurane and sevoflurane did not modify the positive
      lusitropic effects under low and high loads of isoproterenol. CONCLUSION:
      Although isoflurane and sevoflurane have moderate negative inotropic effects,
      they potentiated the positive inotropic effects of alpha- and beta-adrenoceptor
      stimulations but did not modify the positive lusitropic effects of beta
      adrenoceptor stimulation.

PMID- 9605686
TI  - Acetylcholinesterase and butyrylcholinesterase are expressed in the spinal
      meninges of monkeys and pigs.
AB  - BACKGROUND: Acetylcholinesterase inhibition at the spinal level has been shown to
      produce a potent antinociceptive effect. However, the site of cholinesterase
      inhibition is unknown. To determine whether the spinal meninges participate in
      acetylcholine metabolism, the spinal meninges of monkeys and pigs were assayed
      for cholinesterase activity. METHODS: Spinal cord, dura mater, and arachnoid
      mater specimens from anesthetized pigs and monkeys were mechanically homogenized
      and cholinesterase activity was determined quantitatively using a commercially
      available colorimetric assay. The ability of neostigmine to inhibit
      cholinesterase activity in vitro was also measured. Finally, the reverse
      transcriptase polymerase chain reaction (RT-PCR) was used to identify the
      cholinesterase metabolizing enzymes expressed by the spinal meninges. RESULTS:
      All spinal cord and meningeal specimens showed cholinesterase activity. In pigs,
      the dura mater showed less enzyme activity (36 +/- 17.7 U/mg protein) than the
      arachnoid mater (73.4 +/- 30.3 U/mg protein; P < 0.05), and the arachnoid mater
      showed less activity than the spinal cord (131.3 +/- 55.2 U/mg protein; P <
      0.05). In monkeys, the dura mater again showed less cholinesterase activity (45.8
      +/- 20.1 U/mg protein; P < 0.05), whereas cholinesterase activity in the
      arachnoid mater (90.3 +/- 45.9 U/mg protein) and spinal cord specimens (101.9 +/-
      37.5 U/mg protein) were not significantly different. There were no significant
      species-related differences in cholinesterase activity. Neostigmine inhibited
      cholinesterase activity in a log-dose-dependent manner. The RT-PCR identified
      mRNA for acetylcholinesterase and butyrylcholinesterase in monkey pia-arachnoid
      mater. CONCLUSIONS: These data show that the spinal meninges express
      acetylcholinesterase and butyrylcholinesterase; for monkeys, although not pigs,
      the level of cholinesterase activity is comparable with that found in the spinal
      cord. This finding suggests that the meninges may be an important site for
      acetylcholine metabolism and may play a role in the analgesic effect produced by
      intrathecally administered cholinesterase inhibitors.

PMID- 9605687
TI  - Interactions between hypothermia and the latency to ischemic depolarization:
      implications for neuroprotection.
AB  - BACKGROUND: The authors postulated that hypothermic neuroprotection can be
      attributed to a delayed onset of ischemic depolarization. METHODS: Halothane
      anesthetized rats were prepared for near-complete forebrain ischemia. Direct
      current (DC) potential microelectrodes were placed in hippocampal CA1. The
      pericranial temperature was maintained at 31 degrees C, 33 degrees C, 35 degrees
      C, or 37 degrees C (n = 6 per group). Bilateral carotid occlusion with systemic
      hypotension was initiated for 10 min. The time to onset of the DC shift was
      recorded. In a second experiment, rats were assigned to 37 degrees C or 31
      degrees C for 10 min of ischemia, or to 31 degrees C for 14 min of ischemia (n =
      8 per group). These durations of ischemia were defined to allow 9 min of ischemic
      depolarization in the 37 degrees C-10 min and 31 degrees C-14 min groups.
      Neurologic and histologic outcomes were examined 7 days later. RESULTS:
      Hippocampal CA1 time to depolarization increased with decreasing temperature (P <
      0.0001). Time to depolarization was increased by approximately 4 min in the rats
      maintained at 31 degrees C compared with those at 37 degrees C. Time to
      repolarization during reperfusion was not affected by temperature. Increasing the
      duration of ischemia from 10 min to 14 min with the pericranial temperature
      maintained at 31 degrees C resulted in a duration of depolarization that was
      equivalent in the 37 degrees C-10 min and 31 degrees C-14 min groups. However,
      hippocampal CA1 damage was not increased (31 degrees C-10 min = 4 +/- 1% dead
      neurons; 31 degrees C-14 min = 6 +/- 1% dead neurons, 95% CI, -1% to 3%; 37
      degrees C-10 min = 90 +/- 17% dead neurons). CONCLUSIONS: Despite similar
      durations of DC depolarization, outcome in hypothermic rats was markedly improved
      compared with normothermic rats. This indicates that hypothermic neuroprotection
      can be attributed to mechanisms other than the delay in time to onset of ischemic
      depolarization.

PMID- 9605688
TI  - Etomidate does not alter recovery after anoxia of evoked population spikes
      recorded from the CA1 region of rat hippocampal slices.
AB  - BACKGROUND: Etomidate is an anesthetic agent that reduces the cerebral metabolic
      rate and causes minimal cardiovascular depression. Its ability to improve
      recovery after anoxia or ischemia is equivocal. An in vitro neuronal preparation
      was used to examine the action of etomidate on electrophysiologic and biochemical
      parameters during and after anoxia. METHODS: The Schaffer collateral pathway was
      stimulated, and a postsynaptic evoked population spike was recorded from the CA1
      pyramidal cell layer of rat hippocampal slices. Etomidate or propylene glycol,
      its solvent, was present 15 min before, during, and 10 min after anoxia.
      Adenosine triphosphate, sodium, and potassium concentrations were measured at the
      end of anoxia in tissue treated with etomidate, propylene glycol, or with no
      added drugs. RESULTS: Etomidate did not alter recovery after 6 min of anoxia. The
      population spikes from untreated slices recovered to 32% of their preanoxic
      amplitude, and slices treated with 0.5, 3, and 30 microg/ml etomidate recovered
      to 24%, 35%, and 13%, respectively. Slices treated with propylene glycol,
      equivalent to that in 3 and 30 microg/ml etomidate, recovered to 46% and 12%,
      respectively, and this was not significantly different from untreated slices.
      Etomidate did not attenuate the decrease in adenosine triphosphate concentrations
      during anoxia. The increase in sodium and the decrease in potassium during anoxia
      were significantly attenuated by 30 but not by 3 microg/ml etomidate.
      CONCLUSIONS: A range of etomidate concentrations did not significantly alter
      recovery of the evoked population spike after anoxia in rat hippocampal slices. A
      high concentration of etomidate did attenuate the increase in sodium and the
      decrease in potassium during anoxia.

PMID- 9605689
TI  - Nitrous oxide impairs the neutrophil oxidative response.
AB  - BACKGROUND: Nitrous oxide has been shown inconsistently to impair the oxidative
      function of neutrophils. The choice of the stimulus, receptor agonists, or
      stimuli acting independent of receptors seems to determine whether nitrous oxide
      impairs the oxidative functions, suggesting an interference with the cytosolic
      signaling of neutrophils. METHODS: Production of hydrogen peroxide by neutrophils
      was assessed using flow cytometric analysis. N-formyl-methionyl-leucyl
      phenylalanine (FMLP), C5a, dioctanylglycerol, and phorbol-12-myristate-13-acetate
      were used as stimuli. In addition, the expression of receptors for FMLP and the
      cytosolic-free calcium response of cells were measured. RESULTS: Nitrous oxide
      depresses C5a- or FMLP-induced generation of reactive oxygen derivatives in a
      concentration-dependent manner. However, the response with direct activation of
      protein kinase C was unaffected. Further, the number of FMLP receptors and the
      cytosolic calcium response were unaffected. Inhibition of the oxidative response
      was not reversible within the observation period of 4 h. CONCLUSIONS: Nitrous
      oxide inhibited the intracellular signaling of the investigated G-protein-coupled
      receptors for chemotactic peptides. No interference of nitrous oxide with reduced
      nicotinamide adenine dinucleotide phosphate oxidase, the oxidative enzyme system
      of neutrophils, nor with its activation through protein kinase C was detected.

PMID- 9605690
TI  - Pulmonary blood flow redistribution with low levels of positive end-expiratory
      pressure.
AB  - BACKGROUND: Recent studies have questioned the importance of the gravitational
      model of pulmonary perfusion. Because low levels of positive end-expiratory
      pressure (PEEP) are commonly used during anesthesia, the authors studied the
      distribution of pulmonary blood flow with low levels of PEEP using a high spatial
      resolution technique. They hypothesized that if hydrostatic factors were
      important in the distribution of pulmonary blood flow, PEEP would redistribute
      flow to more dependent lung regions. METHODS: The effects of zero cm H2O PEEP and
      5 cm H2O PEEP on pulmonary gas exchange were studied using the multiple inert gas
      elimination technique; the distribution of pulmonary blood flow, using
      fluorescent-labeled microspheres, was also investigated in mechanically
      ventilated, pentobarbital-anesthetized dogs. The lungs were removed, cleared of
      blood, dried at total lung capacity, and then cubed to obtain approximately 1,000
      small pieces of lung (approximately 1.7 cm3). RESULTS: Positive end-expiratory
      pressure increased the partial pressure of oxygen by 6 +/- 2 mmHg (P < 0.05) and
      reduced all measures of ventilation and perfusion heterogeneity (P < 0.05). By
      reducing flow to nondependent ventral lung regions and increasing flow to
      dependent dorsal lung regions, PEEP increased (P < 0.05) the dorsal-to-ventral
      gradient. Redistribution of blood flow with PEEP accounted for 7 +/- 3%, whereas
      structural factors accounted for 93 +/- 3% of the total variance in blood flow.
      CONCLUSIONS: The increase in dependent-to-nondependent gradient with PEEP is
      partially consistent with the gravitationally based lung zone model. However, the
      results emphasize the greater importance of anatomic factors in determining the
      distribution of pulmonary blood flow.

PMID- 9605691
TI  - Intravenous lidocaine attenuates acute lung injury induced by hydrochloric acid
      aspiration in rabbits.
AB  - BACKGROUND: Neutrophils play a crucial role in the pathogenesis of acid-induced
      acute lung injury. Lidocaine inhibits the function of neutrophils. This study
      aimed to determine whether lidocaine attenuates acute lung injury induced by
      hydrochloric acid (HCl) instillation. METHODS: In study 1, rabbits were divided
      into four groups (n = 7 each). Lung injury was induced by intratracheal HCl (0.1
      N, 3 ml/kg) in two groups. The other two groups received saline intratracheally.
      Lidocaine given intravenously (2 mg/ g bolus + 2 mg x kg(-1) x h(-1) infusion)
      was started 10 min before intratracheal instillation in one HCl and one saline
      group, and saline was given intravenously in the other two groups. In study 2,
      rabbits (four groups of seven animals each) received HCl (0.1 N, 3 ml/kg)
      intratracheally. Treatment with intravenous lidocaine was started 10 min before,
      10 min after, or 30 min after acid instillation, or saline was given
      intravenously 10 min before instillation. RESULTS: In study 1, HCl caused
      deterioration of the partial pressure of oxygen (PaO2), lung leukosequestration,
      decreased lung compliance, and increased the lung wet-to-dry weight ratio and
      albumin, interleukin-6 (IL-6), and IL-8 levels in bronchoalveolar lavage fluid.
      Lidocaine pretreatment attenuated these changes. Hydrochloric acid increased
      superoxide anion production by neutrophils and caused morphologic lung damage,
      both of which were lessened by lidocaine. In study 2, lidocaine given 10 min
      after acid instillation was as effective as pretreatment in PaO2, lung mechanics,
      and histologic examination. However, PaO2 changes in lidocaine 30 min after
      injury were similar to those in saline given intravenously. CONCLUSIONS:
      Intravenous lidocaine started before and immediately after acid instillation
      attenuated the acute lung injury, in part by inhibiting the sequestration and
      activation of neutrophils.

PMID- 9605692
TI  - Ketorolac and enoxaparin affect arterial thrombosis and bleeding in the rabbit.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) may interfere with
      hemostasis during the perioperative period, and the combination of NSAID and
      enoxaparin could increase this effect. The aim of this prospective, blinded
      experimental study was to assess these effects using a model of arterial
      thrombosis and bleeding in the rabbit. METHODS: After anesthesia was induced and
      monitors placed, the common carotid arteries were exposed, and 60% stenosis of
      the right common carotid artery was produced. Twenty minutes later, a compression
      injury of the artery was produced that triggered a series of cyclic episodes of
      thrombosis and clot lysis. This was manifested as cyclic flow reductions (CFR;
      measured with an electromagnetic flow meter). After the first flow reduction was
      noted, the rabbits were immediately and randomly assigned to one of four groups
      (n = 10 each) that received intravenous infusions: control, ketorolac (2 mg/kg),
      enoxaparin (0.5 mg/kg), and ketorolac plus enoxaparin (2 mg/kg and 0.5 mg/kg,
      respectively). The number of CFRs that occurred in the subsequent 20-min period
      was used as a measure of treatment effect. The contralateral common carotid
      artery was exposed, and both stenosis and injury were produced. The ability of
      the administered drug to prevent thrombosis was assessed as the number of CFRs
      that occurred during the first 20-min period after vessel injury. In addition,
      both before and after group assignment and drug injection, bleeding times were
      noted and a platelet aggregation test was performed. Laparotomy was followed by a
      spleen section, and the extent of the wound and the amount of splenic bleeding
      were measured. RESULTS: The treatment effect was indicated by the median number
      of CFRs, which was 5.5 in the control group, 1 in the ketorolac group, 2 in the
      enoxaparin group, and 0 in the ketorolac + enoxaparin group. The prevention
      effect was indicated by the median number of CFRs, which was 4 in the control
      group, 0 in the ketorolac group, 2 in the enoxaparin group, and 0.5 in the
      ketorolac + enoxaparin group. Bleeding time was significantly lengthened in the
      enoxaparin and in the ketorolac + enoxaparin groups. Splenic and wound bleeding
      was greater in the ketorolac group. Platelet aggregation was completely inhibited
      in the ketorolac and the ketorolac + enoxaparin groups. CONCLUSIONS: Ketorolac
      had an important antithrombotic activity. The association of enoxaparin with
      ketorolac seemed to lengthen the bleeding time observed with ketorolac.

PMID- 9605693
TI  - Proarrhythmic and antiarrhythmic effects of bupivacaine in an in vitro model of
      myocardial ischemia and reperfusion.
AB  - BACKGROUND: Bupivacaine may have toxic cardiovascular effects when accidentally
      administered by intravascular injection. However, its electrophysiologic effects
      in the presence of myocardial ischemia remain unknown. The authors evaluated the
      electrophysiologic and anti- and proarrhythmic effects of bupivacaine in an in
      vitro model of the ischemic and reperfused myocardium. METHODS: In a double
      chamber bath, a guinea pig right ventricular muscle strip was subjected partly to
      normal conditions and partly to simulated ischemia followed by reperfusion. The
      electrophysiologic effects of bupivacaine were studied at 1, 5, and 10 microM
      concentrations. RESULTS: Bupivacaine (5 and 10 microM) decreased the maximal
      upstroke velocity of the action potential (Vmax) in normoxic conditions and
      further decreased (10 microM) the Vmax decrease induced by ischemic conditions.
      Bupivacaine reduced the mean occurrence time to the onset of myocardial
      conduction blocks (9 +/- 3 min; mean +/- SD; P < 0.005 with 5 and 10 microM,
      compared with 17 +/- 6 min during simulated ischemia with no drug or control),
      and it increased the number of preparations that became inexcitable to pacing
      (55% of preparations, with 1 microM and 100% with 5 and 10 microM, compared with
      17% for the control group). The incidence of spontaneous arrhythmias was reduced
      by 5 and 10 microM bupivacaine during ischemia and reperfusion and was enhanced
      by 1 microM bupivacaine during the ischemic phase. CONCLUSIONS: In guinea pig
      myocardium under ischemic conditions, bupivacaine induced a loss of excitability
      at concentrations of 5 and 10 microM. Proarrhythmic effects observed at 1 microM
      were considered as lower than the cardiotoxic range in normoxic conditions. The
      incidence of reperfusion arrhythmias was decreased at all concentrations.

PMID- 9605694
TI  - Halothane, but not isoflurane, impairs the beta-adrenergic responsiveness in rat
      myocardium.
AB  - BACKGROUND: The aim of this study was to identify the mechanisms by which
      halothane and isoflurane change the myocardial beta-adrenergic signal
      transduction pathway. METHODS: The authors investigated the influence of volatile
      anesthetics on the isometric force of contraction of rat papillary muscles.
      Concentration-response curves for isoproterenol and epinephrine were studied
      under control conditions and in the presence of halothane or isoflurane. In
      radioligand receptor-binding studies, the beta-adrenoceptor affinities for
      isoproterenol and epinephrine were investigated with and without guanosine
      triphosphate. In addition, the isoproterenol-induced cyclic adenosine
      monophosphate accumulations in viable cardiomyocytes in the absence and in the
      presence of halothane were determined by radioimmunoassays. RESULTS: The half
      maximal positive inotropic effect of isoproterenol was reached at a half-maximal
      effective concentration (EC50 value) of 68 nM (33-141 nM; n = 10). A minimum
      alveolar concentration of 1.3 halothane reduced the positive inotropic potency of
      isoproterenol (EC50 = 158 nM [118-214 nM; n = 10; P < 0.01 vs. control]), whereas
      isoflurane did not changed it. This observation held true when the force of
      contraction was stimulated with epinephrine. Halothane (1.3 minimum alveolar
      concentration) depressed beta-adrenoceptor high-affinity binding and beta
      adrenoceptor agonist affinity in radioligand binding assays, an effect not seen
      with isoflurane. Halothane shifted the intracellular cyclic adenosine
      monophosphate response curve of isoproterenol to the right. CONCLUSION:
      Halothane, but not isoflurane, impairs the beta-adrenergic responsiveness in rat
      myocardium by reducing the agonist affinity of the beta-adrenoceptors.

PMID- 9605696
TI  - A method to compare costs of drugs and supplies among anesthesia providers: a
      simple statistical method to reduce variations in cost due to variations in
      casemix.
AB  - BACKGROUND: Comparison of costs among anesthesia providers using "cost per case"
      does not adjust for variations in casemix (such as the type of procedure and
      patient condition). The authors propose an alternative method for comparing costs
      using the American Society of Anesthesiologists' Relative Value Scale (ASARVS)
      system, which incorporates basic units (for the procedure), modifier units (for
      the patient's physical condition), "other" units (such as for the placement of
      invasive monitors), and time units (proportional to the case duration). METHODS:
      Data were obtained from a series of 3,340 anesthetics performed at a tertiary
      hospital. Administered and discarded drug, supply, and fluid costs were used.
      RESULTS: Costs expressed as dollars per ASARVS unit had 54% less variability than
      costs expressed as dollars per case (P < 0.0001). Pearson correlations between
      demographic variables and cost per ASARVS unit ranged from -0.10 to 0.13. Total
      (e.g., quarterly) costs for simulated sets of cases were predicted within 0.0 +/-
      2.3% by multiplying (1) their sum of units and (2) a like set of case's sum of
      costs divided by sum of units. CONCLUSIONS: Costs of anesthetic supplies and
      drugs of a case were more accurately reported as "cost per unit" than as "cost
      per case." This method of calculating the cost of anesthetic drugs and supplies
      has several applications, including (1) comparison of costs among anesthesia
      providers and (2) benchmarking costs among hospitals and anesthesia groups. By
      design, anesthesia providers' time is quantified by their ASARVS units. Together
      anesthesia costs (personnel, supplies, and drugs) are better reported as "cost
      per unit" than as "cost per case."

PMID- 9605695
TI  - Comparison of the effects of bupivacaine and ropivacaine on heart cell
      mitochondrial bioenergetics.
AB  - BACKGROUND: High lipophilic local anesthetics interfere with mitochondrial energy
      metabolism. These metabolic effects could in part explain some of the toxic
      effects of local anesthetics, such as bupivacaine-induced myocardial depression.
      The aim of this study was to compare the bioenergetic effects of the local
      anesthetics bupivacaine and ropivacaine. METHODS: The effects of both local
      anesthetics on mitochondrial energy metabolism were studied in rat heart isolated
      mitochondria and in saponin-skinned left ventricle fibers. Oxygen consumption,
      adenosine triphosphate synthesis, and enzymatic activities of the complexes of
      the respiratory chain were measured. RESULTS: Bupivacaine and ropivacaine acted,
      in isolated mitochondria, as uncouplers between oxygen consumption and
      phosphorylation of adenosine diphosphate. Further, an inhibitory effect of
      mitochondrial respiration was evidenced with both anesthetics during maximal
      respiration and was assigned to a direct inhibition of complex I of the
      respiratory chain. Mitochondrial adenosine triphosphate synthesis was decreased
      by both mechanisms. However, both in isolated mitochondria and in permeabilized
      heart fibers, ropivacaine was less potent than bupivacaine. Adenosine
      triphosphate synthesis was completely suppressed at 3 mM (approximately 0.1%)
      bupivacaine, whereas 3 mM ropivacaine induced only about a 40% inhibition.
      CONCLUSIONS: Ropivacaine disturbs mitochondrial energy metabolism less than
      bupivacaine does. The lower lipid solubility of ropivacaine may be responsible
      for the lesser dose-dependent effects of this drug on mitochondrial
      bioenergetics.

PMID- 9605697
TI  - Perioperative cost-finding analysis of the routine use of intraoperative forced
      air warming during general anesthesia.
AB  - BACKGROUND: Despite the well-documented ability of forced-air warming (FAW) to
      maintain normothermia, it is unclear whether this technique results in a net
      increase or decrease in costs. The authors did a prospective cost-finding study
      comparing FAW with routine thermal care in patients at low risk for perioperative
      complications who were undergoing general anesthesia. METHODS: After
      institutional review board approval was received, 100 patients were studied who
      were having elective surgery scheduled for more than 2 h during general
      endotracheal anesthesia. Patients were randomly assigned to one of two groups:
      FAW or routine thermal care. All patients received a standardized anesthetic.
      Anesthesia providers were blinded to core temperatures and the use of FAW.
      Primary outcomes were those associated with perioperative costs. RESULTS: The
      time from completion of surgical dressing until tracheal extubation was
      significantly reduced in the FAW group (10 +/- 1 min compared with 14 +/- 1 min;
      mean +/- SEM; P < 0.01). There was no demonstrable difference in attainment of
      postanesthesia care unit discharge criteria between the two groups, although the
      FAW group used one less cotton blanket there. The net savings related to the use
      of the FAW depends on the percentage of the intraoperative costs that are fixed
      rather than variable ($15 additional for FAW if all costs are fixed compared with
      $29 savings if all costs were variable). CONCLUSIONS: Routine intraoperative FAW
      significantly reduced time until extubation and use of cotton blankets in the
      postanesthesia care unit. These results suggest that the influence of FAW on net
      total perioperative costs depends on patient and surgical characteristics and
      institutional factors related to cost accounting.

PMID- 9605698
TI  - Carbon dioxide and the cerebral circulation.

PMID- 9605699
TI  - Cecilio Pla's The discovery of anesthesia: the contribution of a painting to
      anesthesia history.

PMID- 9605700
TI  - Cryoablation: a novel approach to neurolysis of the ganglion impar.

PMID- 9605701
TI  - Hypertension and pulmonary edema associated with subconjunctival phenylephrine in
      a 2-month-old child during cataract extraction.

PMID- 9605702
TI  - Endovascular aortic balloon clamp malposition during minimally invasive cardiac
      surgery: detection by transcranial Doppler monitoring.

PMID- 9605703
TI  - Hemothorax and subclavian artery laceration during "J" wire change of a right
      internal jugular vein catheter.

PMID- 9605704
TI  - Recurrent complete heart block in a healthy patient during laparoscopic
      electrocauterization of the fallopian tube.

PMID- 9605705
TI  - Testing the competency of the hemostasis valve in introducer catheters.

PMID- 9605706
TI  - Proinflammatory mediator release after total hip arthroplasty.

PMID- 9605707
TI  - The intensity of the current at which sciatic nerve stimulation is achieved is a
      more important factor in determining the quality of nerve block than the type of
      motor response obtained.

PMID- 9605708
TI  - Spinal cord injury in patients with undiagnosed cervical spine fractures.

PMID- 9605709
TI  - Delayed subarachnoid migration of an epidural Arrow FlexTip Plus catheter.

PMID- 9605710
TI  - Presumed delayed catheter migration.

PMID- 9605711
TI  - Delayed subarachnoid migration of an epidural catheter.

PMID- 9605712
TI  - Another solution to monitoring the electrocardiograph in patients with extensive
      burn injury.

PMID- 9605713
TI  - Transesophageal pulse oximetry for monitoring patients with extensive burn
      injury.

PMID- 9605714
TI  - A potential complication associated with percutaneous tracheostomy with an
      endotracheal tube with a Murphy eye in situ.

PMID- 9605715
TI  - Ventilatory compromise secondary to occlusion of an endotracheal tube's balloon
      air channel by a malpositioned bite block.

PMID- 9605716
TI  - The neurophysiology of dystonia.
AB  - Any model for the physiology of dystonia must be able to explain how dystonia can
      be produced in various circumstances. Brain lesions can cause dystonia;
      responsible sites include the basal ganglia, brainstem, and thalamus, but the
      most common site is the putamen. Dystonia can be hereditary, and genetic linkage
      has been found for both generalized and focal dystonia. The only genetic dystonia
      for which the gene product is known is Segawa disease, a hereditary progressive
      dystonia with marked diurnal fluctuation. The defect is in guanosine triphosphate
      cyclohydrolase I, a gene that makes a cofactor for the synthesis of dopamine,
      which explains why this form of dystonia should be amenable to treatment with
      levodopa. Another example of dystonia in which a disorder of dopamine
      pharmacology appears responsible is the dystonia occurring in Parkinson disease,
      either spontaneously or as a result of treatment. Curiously, the dystonia occurs
      at both peak and trough dopamine levels.

PMID- 9605717
TI  - Atrophy of the corpus callosum, cortical hypometabolism, and cognitive impairment
      in corticobasal degeneration.
AB  - OBJECTIVE: To investigate whether atrophy of the corpus callosum is associated
      with cognitive impairment and cerebral cortical hypometabolism in corticobasal
      degeneration. DESIGN: Prospective clinicoradiological correlation with magnetic
      resonance imaging and positron emission tomography. SETTING: A university
      hospital. PATIENTS: Eight right-handed patients with clinically diagnosed
      corticobasal degeneration (mean+/-SD age, 64+/-8 years). MAIN OUTCOME MEASURES:
      Midsagittal corpus callosum area-skull area ratio (on T1-weighted magnetic
      resonance images), the sum of the scaled scores of the 6 subtests on the Wechsler
      Adult Intelligence Scale-Revised (Digit Span, Arithmetic, Picture Arrangement,
      Object Assembly, Block Design, and Digit Symbol), and cerebral metabolic rate of
      glucose (measured with positron emission tomography by using fludeoxyglucose F 18
      as a tracer). RESULTS: Compared with 36 age-matched right-handed control
      subjects, the patients had significantly decreased callosal area-skull area
      ratio. The reduction in this ratio was greatest in the middle half of the corpus
      callosum. The atrophy of the corpus callosum was accompanied by a decreased mean
      cortical glucose metabolic rate with hemispheric asymmetry and a decrease in the
      sum of the scaled subtest scores of the Wechsler Adult Intelligence Scale
      Revised. CONCLUSIONS: Atrophy of the corpus callosum with middle predominance is
      present in corticobasal degeneration, and this atrophy is associated with
      cognitive impairment and cerebral cortical hypometabolism with hemispheric
      asymmetry. Atrophy of the corpus callosum might reflect the severity of the
      disconnection between cortical regions, and this may be an important factor in
      the development of cerebral cortical dysfunction in corticobasal degeneration.

PMID- 9605718
TI  - Subclinical cerebral complications after coronary artery bypass grafting:
      prospective analysis with magnetic resonance imaging, quantitative
      electroencephalography, and neuropsychological assessment.
AB  - OBJECTIVE: To analyze the frequency and severity of subclinical cerebral
      complications associated with coronary artery bypass grafting (CABG). DESIGN: A
      prospective controlled study using preoperative and postoperative magnetic
      resonance imaging (MRI) of the brain, quantitative electroencephalography (QEEG),
      and detailed neuropsychological and neurologic examinations as potentially
      sensitive indicators of subclinical cerebral injury associated with CABG.
      SETTING: Multimodality evaluation in a tertiary care unit (Kuopio University
      Hospital, Kuopio, Finland). PATIENTS: Thirty-eight patients undergoing elective
      CABG and 20 control patients undergoing other major vascular surgery, mostly
      operations on the abdominal aorta. MAIN OUTCOME MEASURES: Coronary artery bypass
      grafting-associated cerebral complications assessed preoperatively and
      postoperatively by brain MRI, QEEG, detailed neurologic examination, and a
      neuropsychological test battery that evaluates cognitive functions in major areas
      known to be vulnerable to organic impairment (learning and memory, attention,
      flexible mental processing, and psychomotor speed). RESULTS: There were no major
      neurologic complications. A mild hemisyndrome developed in 1 patient who
      underwent CABG and in 1 control patient. Overall, there was no decline in mean
      cognitive performance 3 months after surgery. Electroencephalographic slowing of
      0.5 Hz or more in at least 2 channels occurred in 11 patients who underwent CABG
      and in 1 control patient (P=.03). The postoperative brain MRI scan revealed new
      small ischemic lesions in 8 patients (21%) in the CABG group but in none of the
      control group (P=.03). These new cerebral MRI lesions did not explain
      deterioration in neuropsychological test performance or the QEEG slowing.
      CONCLUSIONS: Coronary artery bypass grafting causes more QEEG alterations and
      small ischemic cerebral lesions that are detectable by MRI than does other major
      vascular surgery. The effect is mainly subclinical, because no statistically
      significant deterioration in mean neuropsychological test performance was
      detected.

PMID- 9605719
TI  - Personality patterns in patients with myotonic dystrophy.
AB  - BACKGROUND: Myotonic dystrophy (DM) is a multisystemic disease. The central
      nervous system is affected by cognitive, affective, and personality disturbances.
      A characteristic behavior was noted from the first clinical descriptions, but no
      definitive conclusions have been drawn despite extensive debate. As DM is a
      genetic disease of well-defined abnormality, it may be a good model for
      understanding the relative contributions of nature and nurture in the building of
      personality traits. OBJECTIVE: To investigate the possibility that there is a
      personality pattern that is characteristic of patients with DM. SUBJECTS AND
      METHODS: The personalities of 15 adult (age range, 20-53 years) patients with DM
      with no, or minimal, muscle weakness were studied by means of the International
      Personality Disorder Examination. The results were compared with those from 14
      matched healthy subjects (age range, 20-54 years) and 12 patients (age range, 22
      50 years) with a mild form of facioscapulohumeral dystrophy. SETTING: The
      Department of Neuromuscular Diseases, Hopital de la Salpetriere, Paris, France.
      RESULTS: Patients with DM exhibited a homogeneous personality profile, with
      statistically significant differences (P<.005) for avoidant, obsessive
      compulsive, passive-aggressive, and schizotypic traits. In both groups of
      controls, the personality profiles were extremely heterogeneous. Personality
      disorders (avoidant personality) were found in 4 of 15 patients with DM.
      CONCLUSIONS: The findings of this study suggest that the personality pattern of
      patients with DM is related to their disease. Their personality disorders are not
      attributable to their adjustment to a disabling condition. By contrast, among the
      patients with DM, the high incidence of avoidant personality, a phenotype poorly
      represented in the general population, supports the idea that it is the
      expression of a primary phenomenon related to a genetic mutation.

PMID- 9605720
TI  - Increased seizure frequency associated with felbamate withdrawal in adults.
AB  - OBJECTIVE: To characterize changes in seizure frequency following felbamate
      withdrawal. DESIGN: Nonrandomized, retrospective chart review of a case series.
      SETTING: Epilepsy program specializing in adults with uncontrolled epilepsy.
      PATIENT POPULATION: Forty-five ambulatory patients withdrawn from felbamate use.
      Patients were included if they had received felbamate for at least 1 month, were
      18 years or older, had accurate seizure frequency documentation, had accurate
      documentation of all antiepileptic drugs, and received the same concomitant
      antiepileptic drugs before and after felbamate therapy, except for the possible
      addition of gabapentin. Patients were excluded if they had hematologic or hepatic
      toxic effects with felbamate, were unable to withdraw from felbamate treatment,
      had a progressive neurologic disorder, or participated in another drug trial.
      METHODS: When information became available on aplastic anemia and hepatotoxicity
      associated with felbamate, all patients were advised to taper their felbamate
      dosage over approximately 2 weeks. They received written instructions for
      tapering felbamate and adjusting concomitant antiepileptic drugs and kept
      calendars to note the number of seizures. The charts of all patients who received
      felbamate were evaluated for adherence to inclusion and exclusion criteria.
      Statistical analysis was performed using a log-linear model for count data. MAIN
      OUTCOME MEASURES: Seizure frequency during the 6 months before initiating
      felbamate therapy served as the baseline. Changes in seizure frequency were
      evaluated by comparing the number of seizures in the month felbamate was tapered
      and the 3 months after felbamate discontinuation with the baseline frequency.
      Comparisons were made between patients who started gabapentin therapy and those
      who did not and between felbamate responders and nonresponders. RESULTS:
      Felbamate withdrawal resulted in a significant (P=.02) increase in seizure
      frequency. Patients receiving gabapentin had a smaller increase in seizure
      frequency, but the difference was not statistically significant. There was no
      statistically significant difference in seizure frequency between felbamate
      responders and nonresponders. CONCLUSIONS: Felbamate withdrawal caused a
      significant increase in seizure frequency over the subsequent 3 months. These
      findings are important for clinical trial design and clinical practice.

PMID- 9605721
TI  - Static and dynamic posturography in patients with vestibular and cerebellar
      lesions.
AB  - OBJECTIVE: To assess the diagnostic usefulness of posturography in 2 well-defined
      patient groups with impaired balance. PATIENTS: Ten control subjects, 10 patients
      with bilateral vestibular loss, and 10 patients with cerebellar atrophy. OUTCOME
      MEASURES: Amplitude, velocity, and frequency of sway in the anteroposterior and
      medial-lateral directions on a static platform, on foam, and on a moving
      platform. RESULTS: Both patient groups consistently had increased sway compared
      with controls, particularly when standing on foam or on a moving platform with
      eyes closed. Sway amplitude and velocity were increased about the same amount.
      The Romberg ratio (sway with eyes closed/sway with eyes open) did not reliably
      differentiate patients from controls or the 2 patient groups from each other.
      Some patients with cerebellar atrophy exhibited a characteristic body tremor at
      about 3 Hz in the anteroposterior direction. CONCLUSIONS: Although sway amplitude
      and velocity were consistently increased in patients with bilateral vestibular
      loss and patients with cerebellar atrophy, none of the posturography measurements
      reliably distinguished the 2 patient groups. The finding of increased frequency
      of sway in the anteroposterior direction in patients with cerebellar atrophy was
      of limited value since the tremor was visible at the bedside.

PMID- 9605722
TI  - Quality of life perception in patients with intractable epilepsy or
      pseudoseizures.
AB  - OBJECTIVES: To contrast and compare self-reported quality of life in patients
      with intractable epilepsy and pseudoseizures and to examine the relationship
      between self-reports and objective measures of cognitive functioning in both of
      these groups. DESIGN: Case series using profile analysis and analysis of
      covariance. SETTING: University epilepsy surgery program. PARTICIPANTS: Forty
      three patients with intractable complex partial seizures of unilateral temporal
      lobe origin and 25 patients with pseudoseizures. MEASURES: Quality of Life in
      Epilepsy Inventory-89; neuropsychological tests assessing verbal memory,
      nonverbal memory, naming, and attention; and the Depression Scale (2) of the MMPI
      2 (Minnesota Multiphasic Personality Inventory). RESULTS: Patients with
      pseudoseizures described themselves as more limited in the physical health domain
      than patients with complex partial seizures. Self-perceptions of cognitive
      functioning were similar between groups, despite the superior performance of
      patients with pseudoseizures on objective measures. Self-perception of cognitive
      dysfunction was related to mood disorder in the pseudoseizure group only, and
      there were no relationships between subjective and objective measurements of
      cognitive status within this group independent of mood disorder. For the complex
      partial seizures group, relationships between subjective and objective measures
      of cognitive function were dependent on the side of seizure onset. CONCLUSIONS:
      Results are consistent with hypotheses that suggest that patients with
      pseudoseizures focus on physical rather than psychological explanations for
      stress, and that this focus is related, at least in a subgroup of patients, to
      mood disorder. Results also provide support for the validity of the Quality of
      Life in Epilepsy Inventory-89 in populations with intractable seizure disorder,
      although there is evidence for a possible floor effect on some of the subscales.

PMID- 9605723
TI  - Epilepsy in childhood: an audit of clinical practice.
AB  - BACKGROUND: It is not known how many children with epilepsy may not need
      treatment with antiepileptic drugs (AEDs), how many respond unsatisfactorily to
      subsequent treatment regimens, and how many achieve "acceptable control" despite
      lack of remission. METHODS: In a prospective multicenter hospital-based study,
      494 children with a broad range of seizure types and types of epilepsy were
      followed up for at least 2 years. There was no standard treatment protocol. We
      describe the treatment strategies applied to these children by the neurologists
      in charge and outcome with respect to remission from seizures. RESULTS: Treatment
      was initially withheld in 29% of the children, and after 2 years 17% still had
      not received any AEDs. There were no serious complications caused by withholding
      treatment. Of the children treated with AEDs, 60% were still using the first AED
      after 2 years; 80% received monotherapy and 20%, polytherapy. Children with
      severe symptomatic epilepsies, such as the West or Lennox-Gastaut syndrome,
      received polytherapy early on in the course of treatment. When 3 regimens had
      failed, the chance of achieving a remission of more than 1 year with subsequent
      regimens was 10%. Nevertheless, 15 of 50 children receiving AEDs in whom the
      "longest remission ever" was less than 6 months did achieve acceptable seizure
      control according to the neurologist in charge of treatment. Hence, of 494
      children, only 35 (7%) developed an intractable form of epilepsy, defined as
      failure to bring seizures under acceptable control. CONCLUSIONS: A substantial
      percentage of children with new-onset epilepsy did not need treatment with AEDs.
      Chances of achieving a good outcome declined with subsequent treatment regimens.
      Not all children with recurrent seizures were suffering from intractable
      epilepsy; some had achieved acceptable control of seizures.

PMID- 9605724
TI  - Cognitive and motor functioning in Parkinson disease: subjects with and without
      questionable dementia.
AB  - BACKGROUND: The nature of cognitive performance in subjects with Parkinson
      disease (PD) without dementia is controversial, perhaps because of failure to
      exclude subjects with unrecognized very mild dementia. OBJECTIVE: To compare
      cognitive and motor functioning in well-characterized subjects with PD without
      overt dementia with healthy elderly control subjects. DESIGN: Subjects'
      conditions were evaluated clinically and psychometrically at entry into a
      longitudinal study of cognitive and motor performance in elderly subjects.
      Measures included a global dementia staging scale, the Washington University
      Clinical Dementia Rating; psychometric tests, including Logical Memory, Digit
      Span, Associate Learning, Information, Block Design, Digit Symbol, Trail-making
      A, Crossing-off, Boston Naming Test, and Word Fluency; and motor measures,
      including finger tapping, gait velocity, reaction time, and movement time.
      SETTING: A university-based research facility. SUBJECTS: There were 3 groups of
      subjects: healthy elderly control subjects (n=43), subjects with PD without
      dementia (n=58), and subjects with PD with questionable dementia (n=22), each
      evaluated at time of entry. RESULTS: As expected, both PD groups were impaired on
      motor measures (gait velocity, finger tapping, and movement time) compared with
      the healthy elderly control group. Neither PD group showed slowing in reaction
      time. The subjects with PD with questionable dementia were more impaired on
      Logical Memory, Block Design, Digit Symbol, and Trailmaking A compared with the
      subjects with PD without dementia. Although free of clinically evident cognitive
      dysfunction (Clinical Dementia Rating score, 0), the PD group without dementia
      was impaired with respect to the healthy elderly control group on all measures
      from the psychometric assessment except Digit Span, Associate Learning, and Word
      Fluency. CONCLUSIONS: The PD group without dementia showed global cognitive
      impairments in comparison with the healthy elderly control group, possibly
      because the healthy elderly control subjects represented idealized aging.
      Although the deficits were of small magnitude, this finding suggests that PD may
      predispose to subclinical cognitive impairment. Longitudinal follow-up is
      required to determine whether subjects with PD destined to develop overt dementia
      can be distinguished from those who do not.

PMID- 9605725
TI  - Changes of circadian blood pressure patterns are associated with the occurence of
      lucunar infarction.
AB  - BACKGROUND: The occurrence of lacunar infarction is closely related to arterial
      hypertension. However, there is only limited and partly controversial knowledge
      regarding the possible pathogenetic role of circadian blood pressure changes.
      OBJECTIVE: To evaluate the relationship between circadian blood pressure rhythm,
      occurrence, and extent of lacunar infarction. METHODS: We analyzed circadian
      blood pressure patterns, other cardiovascular risk factors, and occurrence of
      lacunar infarction in 118 hospitalized patients older than 55 years. Noninvasive
      24-hour blood pressure measurements and magnetic resonance or computed
      tomographic brain imaging were performed in 61 patients with lacunar infarction
      and in 57 control patients. Daytime blood pressure variability was defined as the
      within-subject SD of all systolic and diastolic blood pressure readings during
      the daytime measurement period. Circadian blood pressure variation was defined as
      the average percentage change of nighttime blood pressure values compared with
      the daytime blood pressure values. RESULTS: Patients with lacunar infarction were
      significantly older and showed more often a history of arterial hypertension,
      elevated average daytime blood pressure values, an increased systolic daytime
      blood pressure variability, and a reduced circadian blood pressure variation due
      to an increased incidence of a pathologic nighttime blood pressure increase. No
      significant correlation was found between these parameters and the number of
      lacunae. A logistic regression analysis revealed that a reduced systolic
      circadian blood pressure variation, age, systolic average daytime blood pressure,
      and a history of arterial hypertension were best correlated with the occurrence
      of lacunar infarction. CONCLUSION: Reduced nighttime decline in systolic blood
      pressure may be an important risk factor for the development of lacunar
      infarction in addition to the absolute level of blood pressure and age.

PMID- 9605726
TI  - Pathologic correlates of apraxia in Alzheimer disease.
AB  - OBJECTIVE: To examine the neuroanatomical correlates of apraxia in Alzheimer
      disease. PATIENTS: Twenty-three patients with clinically overt Alzheimer disease.
      DESIGN: Anterograde study and neuropathologic case series. Clinical severity was
      assessed using the Global Deterioration Scale. Ideomotor praxis was examined on
      transitive and intransitive movements and meaningless gestures, and dressing
      ability was evaluated clinically. Constructive praxis was tested using a 3
      dimensional figure copying task. Correlations between neurofibrillary tangle and
      senile plaque densities and praxis test performance were studied using stepwise
      logistic regression models. SETTING: Studies were conducted at the Psychiatric
      and Geriatric Hospitals of the University of Geneva School of Medicine, Geneva,
      Switzerland. MAIN OUTCOME MEASURES: Odds ratios to estimate the associations
      between neurofibrillary tangle and senile plaque densities in each neocortical
      area and the presence of ideomotor, dressing, and constructional apraxia.
      RESULTS: Statistically significant relationships were found between
      neurofibrillary tangle densities in the anterior cingulate cortex and ideomotor
      and dressing apraxia and between neurofibrillary tangle densities in the superior
      parietal, posterior cingulate, and occipital cortex and constructional apraxia.
      Senile plaque counts did not correlate with praxic performance. CONCLUSIONS:
      These results suggest that ideomotor and dressing apraxia are associated with
      mild damage of the anterior cingulate cortex, whereas constructional apraxia is
      related to the disruption of cortical pathways mediating visuospatial cognition
      in Alzheimer disease. Senile plaque densities do not represent a valuable
      pathologic correlate of apraxia in this disorder.

PMID- 9605727
TI  - Wide range of disease onset in a family with Alzheimer disease and a His163Tyr
      mutation in the presenilin-1 gene.
AB  - OBJECTIVES: To describe clinical and genealogical data of a Swedish family with a
      His163Tyr mutation in the presenilin-1 gene (PS1) and to study the Alzheimer
      disease (AD) penetrance in this family. DESIGN: Interviews with relatives,
      studies of medical records, analysis of pedigree, physician examination of the
      affected individuals, and comparison with other families affected by AD with PS1
      mutations. SETTING: Large university-affiliated hospital. PATIENTS AND OTHER
      PARTICIPANTS: Individuals with a His163Tyr mutation in PS1 and their relatives.
      RESULTS: A study of this family with a history of very early AD onset (mean age,
      47 years) has been previously published, but an investigation of the extended
      family revealed a new pattern of onset, with a mean age at onset of 54 years
      (range, 44-65 years). In general, families with AD show a tight cluster of age at
      onset with high penetrance of the disease. However, in this family, an individual
      whose child carries the PS1 mutation died at age 67 years free from cognitive
      symptoms, indicating a very late age at onset or nonpenetration of the disease.
      No association between age at onset and disease duration was found. Furthermore,
      the disease duration did not differ between those having an early onset compared
      with those having a late onset. The earliest clinical manifestations were
      deficits in memory function and disorientation in time and place. Myoclonic jerks
      and epileptic seizures were common symptoms later in the disease. CONCLUSION: The
      large range in age at onset in this family with a uniform genetic basis for the
      disease, a His163Tyr mutation in PS1, supports the existence of other unknown
      genetic or environmental factors of importance for the expression of the AD
      phenotype.

PMID- 9605728
TI  - Hydrocephalus in radiation leukoencephalopathy: results of ventriculoperitoneal
      shunting.
AB  - OBJECTIVE: To assess the clinical benefit of ventriculoperitoneal shunting in
      patients suffering from radiotherapy-induced leukoencephalopathy. DESIGN:
      Retrospective review of a single institutional experience. PATIENTS: Thirty-one
      patients with the postradiotherapy syndrome received ventriculoperitoneal shunts.
      All had a history of cranial irradiation, progressive ventriculomegaly visible on
      neuroimaging scans, and neurologic decline; other causes of hydrocephalus were
      excluded. All 31 patients had cognitive deficits: 30 had gait disturbance and 24
      were incontinent. RESULTS: Twenty-four (80%) of 30 assessable patients achieved
      symptomatic improvement an average of 1.6 months after ventriculoperitoneal
      shunting. Incontinence and gait problems were more likely to improve than
      cognition. Sixteen (53%) of 30 patients achieved a good overall functional
      outcome, and incontinence was the only feature significantly associated with good
      outcome (P=.04). Neither cerebrospinal fluid-opening pressure nor tap tests
      predicted improvement from ventriculoperitoneal shunting. Median duration of
      improvement was 6 months, and median survival after receiving the shunt was 14.5
      months. Shunt-related complications occurred in 10 (33%) of 30 patients, with 1
      fatal outcome. CONCLUSIONS: Our results from ventriculoperitoneal shunting in
      selected patients with radiation-induced hydrocephalus suggest potential benefit.
      Improvement is incomplete and temporary, but can improve quality of life.
      Reliable predictors of successful shunt outcome were not identified.

PMID- 9605729
TI  - Reversible segmental cerebral arterial vasospasm and cerebral infarction:
      possible association with excessive use of sumatriptan and Midrin.
AB  - OBJECTIVE: To describe a patient who developed reversible segmental cerebral
      arterial vasospasm and cerebral infarction while taking excessive amounts of
      sumatriptan succinate and a combination drug (Midrin) consisting of isometheptene
      mucate, 65 mg, dichloralphenazone, 100 mg, and acetaminophen, 325 mg. DESIGN:
      Case report. SETTING: Tertiary care center. PATIENT: A 43-year-old man who
      developed a left occipital infarct after taking a total of 23 sumatriptan
      succinate tablets (25 mg per tablet) and 32 Midrin tablets during a 7-day period
      and who on digital subtraction angiography was shown to have segmental cerebral
      arterial narrowing in multiple vessels. An extensive evaluation for other
      possible risk factors for cerebral infarction was unrevealing. MAIN OUTCOME AND
      RESULTS: Discontinuation of sumatriptan and Midrin regimens and administration of
      nicardipine hydrochloride led to nearly total resolution of the angiographic
      findings, and the patient had no recurrent strokes. CONCLUSIONS: One should
      consider the diagnosis of drug-induced vasospasm in patients with cerebral
      infarction and a history of excessive use of sumatriptan and Midrin. The initial
      angiographic abnormalities may resemble those found in patients with primary
      angiitis of the central nervous system.

PMID- 9605730
TI  - Ischemic optic neuropathy associated with internal carotid artery dissection.
AB  - BACKGROUND: Ischemic optic neuropathy (ION) is an infarction of the anterior or,
      less frequently, posterior part of the optic nerve, usually due to a disease of
      small arteries supplying the optic nerve. Carotid stenosis or occlusions are rare
      causes, and among them, carotid dissections have been so far reported in only 5
      cases. METHODS: We describe 4 patients with ION (2 anterior and 2 posterior) due
      to internal carotid artery dissection of a consecutive series of 110 patients
      with internal carotid artery dissection (3.6%). RESULTS: None of the patients had
      signs of central retinal artery occlusion or ischemic ocular syndrome. Ischemic
      optic neuropathy occurred after a mean of 5.3 days (range, 3-8 days) following
      the first symptom, which was headache in 1 patient, transient monocular blindness
      in 2, and hemispheric transient ischemic attack in 1. One patient had associated
      Homer syndrome, and 2 had severe ipsilateral headache and orbital pain. None of
      the patients developed a cerebral infarction. These features differ from those
      observed in "classic" nonarteritic anterior ION and might therefore point to
      carotid dissection. CONCLUSION: Ischemic optic neuropathy may occur as an early
      sign of carotid dissection: young age, previous transient monocular blindness, an
      association with pain, Horner syndrome, or hemispheric transient ischemic attacks
      are suggestive of this cause and should prompt confirmatory investigations.

PMID- 9605731
TI  - A case of late-onset MELAS.
AB  - We describe a 60-year-old man with MELAS syndrome (mitochondrial myopathy,
      encephalopathy, lactic acidosis, and strokelike episodes) and discuss the
      mitochondrial DNA point mutation 3243. A diagnosis of MELAS should be considered
      in the appropriate clinical setting at any age.

PMID- 9605732
TI  - New-onset psychogenic seizures after surgery for epilepsy.
AB  - BACKGROUND: The emergence of psychogenic seizures after surgery for epilepsy is
      not well recognized. OBJECTIVES: To identify the frequency of psychogenic
      seizures in an 11-year surgical experience and to characterize the patients with
      this complication. METHODS: Ninety-six patients underwent surgery for epilepsy
      between 1985 and 1996. The surgical database was reviewed and all patients who
      experienced postoperative psychogenic seizures were identified. Patients were
      characterized by sex, age, psychopathologic conditions, full-scale IQ, duration
      of epilepsy, surgical procedure, and operative complications. Patients were
      compared with the surgical group as a whole for these variables. SETTING: A
      comprehensive epilepsy center. RESULTS: Five patients were identified: 3 men and
      2 women. Mean full-scale IQ was 73 (range, 66-82). Mean age was 29.8 years
      (range, 22-36 years). Three patients were diagnosed as having psychosis, 1 with
      borderline personality disorder and 1 with generalized anxiety. Operations
      included 4 anterior temporal lobectomies and 1 occipital lobectomy. Two patients
      experienced operative complications. Compared with the surgical cohort, patients
      had a higher frequency of preoperative psychopathologic conditions, lower mean
      full-scale IQ, and a greater occurrence of operative complications. CONCLUSIONS:
      (1) Patients can develop new-onset psychogenic seizures after surgery for
      epilepsy. (2) Low full-scale IQ, serious preoperative psychopathologic
      conditions, and major surgical complications may be risk factors. (3) Atypical
      postoperative seizures should be evaluated with video electroencephalographic
      monitoring before concluding that they are epileptic.

PMID- 9605733
TI  - Familial alternating epilepsia partialis continua with chronic encephalitis:
      another variant of Rasmussen syndrome?
AB  - Two brothers had infantile epilepsia partialis continua alternately involving
      both sides of the body. The children rapidly developed severe psychomotor
      regression and cerebral atrophy. A brain biopsy specimen showed evidence of
      chronic inflammatory changes. Extensive investigation did not provide evidence of
      a specific viral pathogenesis, mitochondrial disorder, or any identifiable
      neurodegenerative genetically determined disorder. This illness has the features
      of Rasmussen chronic encephalitis, in which bilateral involvement is quite
      unusual. Although few patients with bilateral hemispheral involvement have been
      described, to our knowledge there have been no reported cases involving affected
      siblings. The familial disorder described herein may represent yet another
      variant of the classically sporadic and unilateral childhood form. This group of
      disorders is probably immunologically determined.

PMID- 9605734
TI  - Is exposure to aluminum a risk factor for the development of Alzheimer disease?-
      No.

PMID- 9605735
TI  - Is exposure to aluminum a risk factor for the development of Alzheimer disease?-
      Yes.

PMID- 9605736
TI  - Aluminum exposure and risk of Alzheimer disease.

PMID- 9605737
TI  - Myasthenia gravis.

PMID- 9605738
TI  - Apolipoprotein E4 (epsilon) allele does not affect the onset or symptom severity
      in progressive supranuclear palsy.

PMID- 9605739
TI  - Mesial temporal lobe epilepsy.

PMID- 9605740
TI  - High frequency of fibroblast growth factor (FGF) 8 expression in clinical
      prostate cancers and breast tissues, immunohistochemically demonstrated by a
      newly established neutralizing monoclonal antibody against FGF 8.
AB  - Fibroblast growth factor (FGF) 8, also known as androgen-induced growth factor,
      was originally isolated from an androgen-dependent mouse mammary Shionogi
      carcinoma SC-3 cell line, in which it was shown to have androgen-regulated
      properties. We previously demonstrated that Fgf 8 transcripts were detected in
      several human prostate and breast cancer cell lines and that recombinant FGF 8
      was mitogenic to an androgen-sensitive prostate cancer LNCaP cell line. In this
      study, to characterize the roles of FGF 8 in clinical hormone-responsive cancers,
      we established a monoclonal antibody against FGF 8. In Western blots, this
      antibody specifically interacted with a FGF 8b isoform that was identical between
      mouse and human but was not identical to other murine 8a and 8c isoforms. In a
      cell growth assay using SC-3 cells, the newly established anti-FGF 8 antibody
      blocked androgen- and FGF 8-stimulated growth but not basic FGF-stimulated
      growth. Immunohistochemical analyses by use of the established anti-FGF 8
      antibody demonstrated that FGF 8 was frequently expressed in human prostate
      cancers, appearing in 40 of 43 cases (93%), whereas both prostatic hyperplasia
      specimens and normal prostate tissues included in biopsy specimens were negative
      for FGF 8 expression. On the other hand, FGF 8 was detected in normal ductal and
      lobular epithelial cells in breast tissues. FGF 8 was also frequently expressed
      in various breast diseases, including fibroadenomas (5 of 5 cases, 100%),
      intraductal papillomas (3 of 3 cases, 100%), ductal hyperplasias (3 of 6 cases,
      50%), and breast cancers (8 of 12 cases, 67%). Androgen receptors were also
      immunohistochemically detected in FGF 8-positive prostate cancers (40 of 40
      cases, 100%) and FGF 8-positive breast diseases (17 of 19 cases, 89%). These
      findings strongly suggest that FGF 8 is involved in hormone-related tumorigenesis
      of the prostate and breast.

PMID- 9605741
TI  - Up-regulation of Fas (APO-1/CD95) ligand and down-regulation of Fas expression in
      human esophageal cancer.
AB  - Fas (APO-1/CD95) is a cell surface receptor that mediates apoptosis when it
      reacts with Fas ligand (FasL) or Fas antibody. In this study, we analyzed Fas and
      FasL expression in normal esophageal mucosa and esophageal squamous cell
      carcinomas. Reverse transcriptase-PCR revealed that Fas, soluble Fas, and FasL
      were expressed in all eight esophageal squamous carcinoma cell lines analyzed.
      Furthermore, it was demonstrated that FasL expressed in esophageal carcinoma
      cells is functional because coculture experiments using FasL-expressing TE-15
      esophageal carcinoma cells resulted in apoptosis of Jurkat T leukemia cells,
      which are sensitive to Fas-mediated apoptosis. Immunohistochemistry of Fas and
      FasL showed that they are constitutively expressed in normal esophageal mucosa,
      FasL being predominantly in the basal and suprabasal layers, whereas Fas is in
      more differentiated layers, i.e., rows of polyhedral cells of the intermediate
      layers and squamous cells forming the outer layers. In 18 of 19 invasive
      esophageal squamous cell carcinomas, FasL expression was found in >50% of tumor
      cells. In contrast, most tumors (15 of 19, 79%) either showed no Fas expression
      or showed expression in <5% of tumor cells. These alterations were already
      detected in dysplasia and carcinoma in situ. These results suggest that up
      regulation of FasL and down-regulation of Fas expression are early and frequent
      events associated with the evolution of esophageal squamous cell carcinomas.

PMID- 9605742
TI  - Distinct patterns of E-cadherin CpG island methylation in papillary, follicular,
      Hurthle's cell, and poorly differentiated human thyroid carcinoma.
AB  - Expression of the invasion/metastasis suppressor, E-cadherin, is diminished or
      lost in thyroid carcinomas. Yet, mutational inactivation of E-cadherin is rare.
      Herein, we show that this loss is associated with hypermethylation of the E
      cadherin 5' CpG island in a panel of human thyroid cancer cell lines. This
      aberrant methylation is evident in 83% of papillary thyroid carcinoma, 11% of
      follicular thyroid carcinoma, 40% of Hurthle's cell carcinoma, and 21% of poorly
      differentiated thyroid carcinomas. Contrary to previous reports, the majority of
      these poorly differentiated thyroid carcinomas express E-cadherin, but often
      within the cytoplasm rather than at the cell surface. Together, our data indicate
      that the invasion/metastasis suppressor function of E-cadherin is frequently
      compromised in human papillary, Hurthle's cell, and poorly differentiated thyroid
      carcinoma by epigenetic and biochemical events.

PMID- 9605743
TI  - Helicobacter pylori infection enhances N-methyl-N-nitrosourea-induced stomach
      carcinogenesis in the Mongolian gerbil.
AB  - No previous report has demonstrated the relationship between Helicobacter pylori
      (HP) infection and gastric carcinogenesis in an experimental animal model. A
      total of 170 male Mongolian gerbils (MGs) were divided into nine groups (18 < or
      = n < or = 20 for each group). MGs of four groups were inoculated with HP before
      or after continuous N-methyl-N-nitrosourea (MNU) administration via the drinking
      water. Both intestinal-type and diffuse-type adenocarcinomas, including signet
      ring-cell carcinomas, were found at 40 weeks after the study commenced, but only
      in the HP inoculation groups with MNU exposure and not in the MNU alone or HP
      inoculation alone control groups. The present findings demonstrate that HP
      infection increases the incidence of MNU-induced adenocarcinoma of the glandular
      stomach in MGs.

PMID- 9605744
TI  - Carcinogens preferentially bind at methylated CpG in the p53 mutational hot
      spots.
AB  - The major mutational hot spots in human cancers occur at CpG sequences in the p53
      gene. It is generally presumed that the majority of mutations at these sites
      result from the endogenous deamination of methylated cytosine. Using a UvrABC
      incision method, we have found that cytosine methylation greatly enhances guanine
      alkylation at all CpG sites in the p53 gene by a variety of carcinogens,
      including benzo(a)pyrene diol epoxide, benzo(g)chrysene diol epoxide, aflatoxin
      B1 8,9-epoxide, and N-acetoxy-2-acetylaminofluorene. These findings suggest that
      mutational hot spots at methylated CpG sequences in the p53 gene may be a
      consequence of preferential carcinogen binding at these sites.

PMID- 9605745
TI  - Mutation, allelotyping, and transcription analyses of the p73 gene in prostatic
      carcinoma.
AB  - A novel gene, p73, encoding a protein with significant homology to p53, was
      recently identified at 1p36. To investigate penetrance of p73 in prostatic
      carcinogenesis, mutation, allelotyping, and transcription analyses of p73 were
      performed in prostatic carcinoma. No types of mutation causing amino acid
      substitutions or frameshifts were found in 106 cases examined. Loss of
      heterozygosity in the gene was found in 2 of 38 cases (5.3%). Various expression
      levels of p73 alpha variant were observed in tumor compared with those in normal
      tissue. These data suggest that the p73 gene is not playing an essential role,
      but expression of p73 may associate with tumor growth in prostatic
      carcinogenesis.

PMID- 9605746
TI  - Expression of Fas(APO-1/CD95) in tumor-infiltrating and peripheral blood
      lymphocytes in patients with renal cell carcinoma.
AB  - The functional expression of Fas-ligand on tumor cells reported in a variety of
      neoplasms has been proposed by several groups as a mechanism of tumor escape from
      immunological detection. To better support this hypothesis, we have evaluated and
      quantified for the first time the presence of the Fas(CD95)-R molecule on tumor
      infiltrating lymphocytes and on matched peripheral blood lymphocytes (PBLs) of
      renal cell cancer patients. By two-color flow cytometry we have detected a
      significant increase in the Fas(CD95)-R expression on tumor-infiltrating
      lymphocytes compared with matched patient and normal volunteer PBLs. We also
      observed a decreased expression of the Fas(CD95)-R expression on PBLs from renal
      cell cancer patients compared with normal healthy controls. The Fas(CD95)-R
      expression was observed predominantly on the CD4+ subset in all three groups.
      These different distributions of the Fas(CD95)-R molecule support the hypothesis
      that the Fas(CD95)-R/Fas(CD95)-L pathway and tumor microenvironment play a major
      role in the modulation of T-cell function and differentiation to either memory
      and activation or apoptosis.

PMID- 9605747
TI  - Location of several putative genes possibly involved in human breast cancer
      progression.
AB  - Cancer is a genetic disease resulting from an accumulation of genetic
      abnormalities in various regulatory genes. Most studies on genetic alterations in
      human breast cancer have involved primary tumors. The possible involvement of
      specific tumor suppressor genes in the later stages of cancer progression is
      poorly documented. We investigated allelic losses associated with breast cancer
      progression by analyzing 55 polymorphic markers on 11 autosomal chromosomes in a
      series of 49 relapses (23 local recurrences and 26 distant metastases). All of
      the loss of heterozygosity (LOH) regions reported in primary breast tumors were
      frequent in both series of relapses. These results suggest that the allelic
      losses that are common to the different series of samples occur very early during
      tumor progression. This study points to candidate metastasis-related genes
      targeted by LOH on chromosome arms 3p21.3, 16q22.2-23.2, and, possibly, 7q31 but
      provides no clear evidence of LOH affecting previously described metastasis
      related genes such as NME1, MTS1, and TSG101.

PMID- 9605748
TI  - Somatic mutations in LKB1 are rare in sporadic colorectal and testicular tumors.
AB  - Germ-line mutations in a serine/threonine kinase gene, LKB1, were recently shown
      to underlie Peutz-Jeghers syndrome (PJS), a hereditary disorder that predisposes
      to benign and malignant tumors of multiple organ systems. Most mutations that
      have been described thus far dramatically change the predicted protein and are
      likely to be of an inactivating nature. This observation and a previous
      observation that the LKB1 locus is often deleted in PJS polyps suggest that the
      gene may function as a tumor suppressor. We examined whether somatic mutations in
      this gene are present in sporadic carcinomas of the colon and testis, tumors that
      are characteristic of PJS. First, 20 randomly selected colorectal and 28
      testicular tumors were analyzed by single-strand conformation polymorphism
      analysis. No mutations in LKB1 were found in colorectal tumors. One testicular
      tumor displayed a heterozygous missense type variant, in which glycine 163 was
      changed to aspartic acid. This change was absent in the DNA of normal tissue. To
      better focus our efforts, we tested 75 additional colon carcinomas for loss of
      heterozygosity at 19p, where LKB1 is localized. Of 75 samples analyzed, 50 were
      informative with a closely linked marker, D19S886, and 13 (26%) of these
      displayed loss of heterozygosity. The 13 tumors were scrutinized for LKB1
      mutations by genomic sequencing. This analysis revealed no changes. Together,
      these findings suggest that somatic mutations of LKB1 are not frequent in
      colorectal and testicular cancer.

PMID- 9605749
TI  - Wild-type and mutant forms of p53 activate human topoisomerase I: a possible
      mechanism for gain of function in mutants.
AB  - p53-interacting proteins from mouse epidermal cells and human myelogenous
      leukemia cells were isolated by affinity chromatography using glutathione S
      transferase (GST)-p53 fusion proteins. One of these proteins was topoisomerase I,
      whose interaction with p53 was recently reported. A carboxyl-terminal fragment
      containing the last 92 amino acids of p53 (GST-299-390) was sufficient for
      binding to topoisomerase I. Nanomolar concentrations of either GST-p53 or GST-299
      390 enhanced the catalytic activity of purified human topoisomerase I. Purified
      wild-type human p53 and point mutants Ser-239, Ser-245, and His-273 were
      equivalent in their enhancement of human topoisomerase I activity. Because
      topoisomerase I is thought to promote genetic recombination, competence to
      enhance topoisomerase I catalytic activity coupled with a deficiency in
      transcriptional activity may be a mechanism for gain of function in mutant p53
      proteins.

PMID- 9605750
TI  - Frequent PTEN/MMAC mutations in endometrioid but not serous or mucinous
      epithelial ovarian tumors.
AB  - Epithelial ovarian cancer comprises three major histological subtypes (serous,
      mucinous, and endometrioid), and it is becoming clear that the developmental
      pathways for these subtypes are fundamentally different. In particular,
      endometrioid ovarian cancers probably arise by the malignant transformation of
      ectopic endometrial implants called endometriosis and not the ovarian surface
      epithelium. The PTEN/MMAC gene on chromosome 10q23 is a tumor suppressor
      implicated in the pathogenesis of a wide variety of malignancies, but to date,
      somatic mutations in PTEN have not been identified in studies of predominantly
      serous ovarian cancers. In endometrial cancers, PTEN mutations are very common in
      tumors of the endometrioid type but have rarely been found in serous types, and
      we hypothesized that a similar histological subtype bias might be occurring in
      ovarian cancer. We have analyzed 81 ovarian tumors, including 34 endometrioid, 29
      serous, 10 mucinous, and 8 clear cell tumors, for loss of heterozygosity (LOH) on
      10q23 and for mutations in all 9 coding exons of PTEN. LOH was common among the
      endometrioid (43%) and serous (28%) tumors but was infrequent among the other
      histological subtypes. Somatic PTEN mutations were detected in seven (21%) of the
      endometrioid tumors, and in all informative cases, the mutation was accompanied
      by loss of the wild-type allele. One mucinous tumor without 10q23 LOH was shown
      to harbor two somatic PTEN mutations. In this tumor, the histological appearance
      of the mucinous areas was atypical, and the mucinous areas contained foci of
      endometrioid differentiation. The majority of tumors with PTEN mutations were
      grade 1 and/or stage 1, suggesting that inactivation of PTEN is an early event in
      ovarian tumorigenesis. No PTEN mutations were found among the serous or clear
      cell tumors. The identification of frequent somatic PTEN mutations in
      endometrioid ovarian tumors indicates that it plays a significant role in the
      etiology of this subtype. The absence of mutations in other histological subtypes
      is consistent with the hypothesis that epithelial ovarian cancers arise through
      distinct developmental pathways.

PMID- 9605751
TI  - Tirapazamine is metabolized to its DNA-damaging radical by intranuclear enzymes.
AB  - Tirapazamine (TPZ), a new anticancer drug that is currently in Phase II and III
      clinical trials, has a unique mechanism of action. Its cytotoxicity is selective
      for hypoxic cells in solid tumors and results from DNA damage produced by a free
      radical, which is generated by enzymatic reduction of the parent molecule.
      However, there is no agreement as to which enzyme(s) are involved. Here, we have
      measured both DNA damage and TPZ metabolism in A549 human lung cancer cells and
      in isolated nuclei derived from the cells. We show that, although the nuclei
      metabolize TPZ at a rate that is only 20% of that of whole cells, they have
      levels of DNA damage that are similar to those of the cells. We also show that
      TPZ radicals that are formed outside nuclei do not contribute to intranuclear DNA
      damage. Thus, essentially all of the DNA damage from TPZ results from radicals
      generated within the nucleus, and the 80% of the drug metabolism that occurs in
      the cytoplasm is probably irrelevant for the activity of this drug in killing
      hypoxic cells.

PMID- 9605752
TI  - Induction of apoptosis and activation of interleukin 1beta-converting enzyme/Ced
      3 protease (caspase-3) and c-Jun NH2-terminal kinase 1 by benzo(a)pyrene.
AB  - Benzo(a)pyrene (BaP), a prototype of polycyclic aromatic hydrocarbons (PAHs), is
      a potent procarcinogen generated during the combustion of fossil fuels and
      cigarette smoke. In addition to the carcinogenic and mutagenic effects, BaP and
      other PAHs, including 7,12-dimethylbenz[a]anthracene and 2,3,7,8
      tetrachlorodibenzo[p]dioxin, have been shown to induce programmed cell death or
      apoptosis. However, the molecular mechanisms by which PAHs such as BaP induce
      apoptosis are not clear. To investigate the molecular events leading to apoptosis
      induced by BaP, we studied the involvement of the interleukin 1beta-converting
      enzyme (ICE)/Ced-3 family of proteases (caspases) and c-Jun NH2-terminal kinase 1
      (JNK1), which have been shown to mediate numerous extracellular stimuli-induced
      apoptosis. On treatment of mouse Hepa 1c1c7 hepatoma cells with BaP, the
      induction of apoptosis, as determined by genome digestion, was observed at
      concentrations of 1-30 microM after 24 h of treatments. Importantly, at the
      apoptosis-inducing concentrations, BaP also induced the activation of an ICE/Ced
      3 cysteine protease caspase-3 but not caspase-1 (ICE). The activation of caspase
      3 by BaP preceded apoptosis. Furthermore, a specific inhibitor of caspase-3-like
      proteases, acetyl-Asp-Glu-Val-Asp-aldehyde, significantly blocked caspase-3
      activity and attenuated apoptosis induced by BaP. Treatment with BaP also caused
      a time- and dose-dependent activation of JNK1 activity. Interestingly, a much
      lower concentration (5 nM), as well as much earlier kinetics, were observed in
      JNK1 activation as compared with caspase-3 activation or induction of apoptosis
      by BaP. In summary, our results demonstrate that BaP induced apoptosis in the
      mouse hepatoma Hepa1c1c7 cell line via a caspase-dependent pathway, which may be
      independent of JNK activation.

PMID- 9605753
TI  - Genetic polymorphisms in catechol-O-methyltransferase, menopausal status, and
      breast cancer risk.
AB  - Polymorphic catechol-O-methyltransferase (COMT) catalyzes the O-methylation of
      estrogen catechols. In a case-control study, we evaluated the association of the
      low-activity allele (COMT(Met)) with breast cancer risk. Compared to women with
      COMT(Val/Val), COMT(Met/Met) was associated with an increased risk among
      premenopausal women [odds ratio (OR), 2.1; confidence interval (CI), 1.4-4.3] but
      was inversely associated with postmenopausal risk (OR, 0.4; CI, 0.2-0.7). The
      association of risk with at least one low-activity COMT(Met) allele was strongest
      among the heaviest premenopausal women (OR, 5.7; CI, 1.1-30.1) and among the
      leanest postmenopausal women (OR, 0.3; CI, 0.1-0.7), suggesting that COMT,
      mediated by body mass index, may be playing differential roles in human breast
      carcinogenesis, dependent upon menopausal status.

PMID- 9605754
TI  - A Bcl-xL transgene promotes malignant conversion of chemically initiated skin
      papillomas.
AB  - The role of apoptosis in the pathogenesis of skin cancer was analyzed in mice
      bearing a Bcl-xL transgene expressed under the control of the keratin 14
      promoter. No spontaneous tumors developed in the skin of these transgenic mice.
      Bcl-xL transgenics also failed to develop skin lesions following treatment with
      the chemical mutagen 9,10-dimethyl-1,2-benzanthracene, or the tumor promoter O
      tetradecanoylphorbol-13-acetate. However, Bcl-xL transgenics developed a two-fold
      greater number of benign papillomas than control littermates following treatment
      with the combination of 9,10-dimethyl-1,2-benzanthracene and O
      tetradecanoylphorbol-13-acetate. More significantly, Bcl-xL transgenic mice
      developed invasive squamous cell carcinoma earlier and more frequently than wild
      type controls in response to the chemical agents. These data suggest that Bcl-xL
      cannot functionally substitute for a mutagenic initiator or mitogenic promoter in
      tumorigenesis. In contrast, Bcl-xL overexpression can dramatically increase the
      malignant conversion rate of benign tumors, suggesting that inhibition of
      apoptosis can contribute to tumor progression.

PMID- 9605755
TI  - Telomerase activity and alterations in telomere length in human brain tumors.
AB  - Telomerase activity was examined in 170 human brain tumor tissues, and terminal
      restriction fragment (TRF) length was examined in 152 of the 170. Telomerase
      activity was detected in 61.7% (66 of 107) of the neuroepithelial tumors.
      However, the detection rates of telomerase activity were widely different for
      different histopathological entities. In the case of astrocytic tumors, the
      detection rate was 20.0% (3 of 15) for grade II astrocytomas, 40.0% (6 of 15) for
      anaplastic astrocytomas, and 72.3% (34 of 47) for glioblastomas. The mean TRF
      length of the tumors with telomerase activity was significantly shorter than that
      of the tumors with undetectable telomerase activity for each tumor entity. In
      grade II and anaplastic astrocytomas, telomerase activity was an indicator of
      early histological progression and reduced survival of the patients, although
      there was no difference in MIB-1 staining indices between the tumors with and
      without telomerase activity at onset. In three astrocytic tumors, concurrence of
      telomere shortening and telomerase reactivation was observed at recurrence; in
      these cases, tumors progressed to a higher grade. Ten glioblastomas that
      progressed from lower-grade tumors exhibited telomerase activity, and their TRF
      lengths were reduced in 80% (8 of 10). In contrast, telomerase activity was
      detected in only 63.3% (19 of 30; P < 0.05) and the TRF length remained
      compatible with normal values in 56.7% (17 of 30; P < 0.01) of de novo
      glioblastomas. Thus, telomerase activity strongly correlated with potential tumor
      progression in the short term as well as with progression itself of the
      astrocytic tumors, whereas telomeres may still have been in the process of
      shortening in some of the de novo glioblastomas. High telomerase activity was
      exhibited in all primitive neuroectodermal tumors, anaplastic oligoastrocytomas,
      neuroblastomas, and oligodendrogliomas. TRF length was reduced in the majority
      (14 of 15) of three previously high-grade tumors, whereas it was compatible with
      that of normal brain tissues in the oligodendrogliomas, suggesting that
      telomerase activity with shortened telomeres correlates with the aggressive
      growth of high-grade neuroepithelial tumors. Tumor cell lines could be
      established from 17.2% (5 of 29) of neuroepithelial tumors with telomerase
      activity but not from tumors without this activity (P < 0.05), suggesting that
      telomerase reactivation is an essential event in the neuroepithelial cell
      immortalization in vitro. In nonneuroepithelial tumors, telomerase activity was
      detected in malignant tumors, such as germ cell tumors, lymphomas, metastatic
      adenocarcinomas, hemangiopericytomas, and an anaplastic meningioma. In contrast,
      such activity was not detected in benign tumors, including meningiomas, pituitary
      adenomas, hemangioblastomas and schwannomas, except for one hemangioblastoma that
      recurred four times and displayed malignant features at the fourth recurrence.
      These findings suggest that telomerase activity can be an index of malignant
      potential or malignancy itself in nonneuroepithelial brain tumors.

PMID- 9605756
TI  - Inhibition of microtubule assembly in tumor cells by 3-bromoacetylamino
      benzoylurea, a new cancericidal compound.
AB  - We have synthesized a new compound, 3-bromoacetylamino benzoylurea (3-BAABU),
      which showed strong cancericidal activity by inducing irreversible mitotic arrest
      and subsequently apoptosis in human T cell leukemic cells (CEM), human
      biphenotypic leukemic cells (SP), a human prostate cancer cell line (PC-3),
      murine melanoma cells (B-16), and murine lymphoma/leukemia cells (EL4) in vitro
      with an ID50 in the range of 0.013-0.07 microg/ml (0.04-0.22 microM). Treatment
      of tumor cells for 12-24 h with 3-BAABU resulted in mitotic arrest at
      prometaphase/metaphase/anaphase, with separation and dispersion of chromosomes
      and with the absence of mitotic spindle apparatus in cytoplasm. Treatment with 3
      BAABU had no cytotoxic and mitotic blocking effect in normal human lymphocytes,
      proliferating fibroblast cells (3T3), or proliferating myocardial cells (MOT).
      Cell cycle analyses showed that most treated leukemic cells accumulated at M
      phase 12 h after treatment. By the end of 48 h of treatment, the cells underwent
      apoptosis with DNA fragmentation. 3-BAABU inhibited the assembly of microtubules
      from tubulin but did not interfere with the disassembly of microtubules. The
      presence and the position of bromine and urea groups on the benzoic ring are the
      determining factors for its inhibition of microtubule assembly. Replacing bromine
      with chlorine yielded much less mitotic blocking activity and increased the ID50
      40-fold. Substitution of the urea group with ethyl ester abrogated the activity
      of blocking mitosis but induced apoptosis. Moving the bromoacetylamino group from
      the 3-position to the 4-position removed blocking activity for mitosis but
      induced necrosis. These results suggest that 3-BAABU possesses a unique and
      functional structure and is a potential agent for cancer chemotherapy.

PMID- 9605757
TI  - Modulation of Bcl-2 protein levels by an intracellular anti-Bcl-2 single-chain
      antibody increases drug-induced cytotoxicity in the breast cancer cell line MCF
      7.
AB  - Extensive experimental evidence suggests that Bcl-2 promotes cell survival by
      preventing the onset of apoptosis induced by a variety of stimuli. In addition,
      Bcl-2 expression has been correlated with resistance and poor response to
      chemotherapy in a number of cell types. Therefore, this protein represents a
      logical target for gene therapy strategies designed to achieve selective gene
      product ablation. In this study, we have developed an approach based upon
      intracellular expression of single-chain antibodies (sFvs) to achieve modulation
      of Bcl-2 protein levels in target cells. Using a transient expression system, we
      show that this intracellular anti-Bcl-2 sFv mediates specific reduction of Bcl-2
      levels. This effect significantly enhances drug-mediated cytotoxicity in Bcl-2
      overexpressing tumor cells, whereas transfection of the anti-Bcl-2 sFv did not
      affect the growth rate of the tumor cell lines. This method thus represents a
      novel and efficient way to selectively abrogate the activity of Bcl-2.

PMID- 9605758
TI  - Pharmacodynamics of immediate and delayed effects of paclitaxel: role of slow
      apoptosis and intracellular drug retention.
AB  - The kinetics of the time-dependent antitumor effects of paclitaxel are not fully
      understood; some literature reports indicate a higher activity by prolonging
      treatment durations, whereas other reports indicate no enhancement under in vitro
      conditions. The present study was designed to address this controversy and to
      determine the mechanism of the higher cytotoxicity associated with longer
      treatment durations. Six human epithelial cancer cell lines (bladder RT4, breast
      MCF7, pharynx FaDu, ovarian SKOV3, and prostate PC3 and DU145) were used. To
      determine whether the higher activity observed for the longer treatment durations
      is due to a delayed exhibition of drug effects and/or a reflection of cumulative
      effects that required a continuous drug exposure, cells were treated with
      paclitaxel for 3-96 h and then either: (a) immediately processed for drug effect
      measurement; or (b) washed, incubated in drug-free medium, and processed for drug
      effect measurement at 96 h. The overall drug effect (i.e., combination of
      cytostatic and apoptotic effects) was determined by the sulforhodamine B assay,
      which measures the cellular protein. In addition, to determine whether apoptosis
      occurs with a time delay, apoptosis was measured in cells that were collected
      immediately after drug treatment for various durations or in cells that were
      treated with drugs for 3 h but collected at later time points. Apoptosis was
      determined using agarose gel electrophoresis and by measuring the cytoplasmic DNA
      histone complex using ELISA. The contribution of the intracellularly retained
      drug to the delayed drug effect was studied by characterizing the kinetics of
      cellular drug uptake and efflux and by examining the effect of removal of the
      intracellularly retained drug. All six cell lines showed similar results, as
      follows: (a) paclitaxel produced cytotoxicity that was exhibited immediately
      after treatment (immediate effect) and after treatment was terminated (delayed
      effect); (b) the immediate and delayed effects showed different pharmacodynamics.
      The immediate effect increased with treatment duration and drug concentration.
      For the delayed effect, all treatments produced the same maximum effect at 96 h,
      although treatments for < or = 12 h showed higher IC50s than longer treatments,
      whereas treatments for > or = 24 h showed indistinguishable IC50s; (c) treatment
      for as brief as 3 h was sufficient to induce apoptosis, which occurred with a lag
      time of about 24 h, although longer treatments produced a greater extent of
      apoptosis; (d) The intracellular and extracellular concentrations reached an
      equilibrium at approximately 5 h, which rules out slow and/or insufficient uptake
      as the cause of the lower effects at shorter treatment times (i.e., < 24 h); (e)
      upon removal of drug-containing medium, the amount of drug retained
      intracellularly was about 10% of the applied dose and was reduced to
      approximately 0.5% after three successive washes, separated by 3-h equilibration
      periods; and (f) the delayed effect of the 3-h treatment was largely due to the
      drug retained intracellularly, whereas the delayed effect of the 24 h treatment
      was independent of the drug retained intracellularly. In conclusion, in human
      epithelial cancer cells, paclitaxel-induced cytotoxicity occurred after
      termination of drug treatment, which was partly due to the slow manifestation of
      apoptosis and partly due to the significant amount of drug retained
      intracellularly. Based on these findings and recognizing that some previous
      studies measured the immediate effect whereas the other studies measured the
      delayed effect, we propose that the conflicting data in the literature regarding
      the effect of treatment duration on paclitaxel activity under in vitro conditions
      are in part due to the different pharmacodynamics of the immediate and delayed
      drug effects. Furthermore, differences in the delayed effects for treatments of <
      24 h and the minimal differences for treatments of > or = 24 h indicate that th

PMID- 9605759
TI  - Molecular analysis of the HLA-A2 antigen loss by melanoma cells SK-MEL-29.1.22
      and SK-MEL-29.1.29.
AB  - Due to the potential clinical relevance of HLA class I antigen losses in melanoma
      cells and the scanty information about the molecular mechanisms underlying these
      defects, we have characterized the cause of the HLA-A2 antigen loss by autologous
      melanoma cell lines SK-MEL-29.1.22 and SK-MEL-29.1.29. Both cell lines have
      structural defects of HLA-A2 genes, which cause lack of their transcription. In
      SK-MEL-29.1.22 cells the 5'-flanking region, exon 1, intron 1, and a region at
      the 5' end of exon 2 of the HLA-A2 gene are deleted. The breakpoint of the HLA-A2
      gene, which is recombined with a DNA fragment of unknown origin, was localized
      between two GTTCG sequence repeats at position 101 of exon 2. These repeats may
      provide the sequence basis for misalignment in the process of DNA deletion. In SK
      MEL-29.1.29 cells, loss of HLA-A2 antigens, as well as of HLA-B44 and HLA-Cw5
      alleles, is caused by the loss of one copy of chromosome 6. Down-regulation of
      the expressed HLA class I alleles in the two HLA-A2 loss variants and in the
      parental cells was found to be associated with a low TAP1 expression and a
      reduced function of peptide transporters. Therefore, multiple defects result in
      loss or down-regulation of HLA class I alleles in SK-MEL-29.1.22 and SK-MEL
      29.1.29 melanoma cells.

PMID- 9605760
TI  - Glial cell line-derived neurotrophic factor/neurturin-induced differentiation and
      its enhancement by retinoic acid in primary human neuroblastomas expressing c
      Ret, GFR alpha-1, and GFR alpha-2.
AB  - Neuroblastomas often undergo spontaneous differentiation and/or regression in
      vivo, which is at least partly regulated by the signals through neurotrophins and
      their receptors. Recently, glial cell line-derived neurotrophic factor (GDNF) and
      a second family member, neurturin (NTN), have been found to mediate their signals
      by binding to a heterotetrameric complex of c-Ret tyrosine kinase receptors and
      glycosylphosphatidylinositol-linked proteins, GFR alpha-1 (GDNFR-alpha) or GFR
      alpha-2 (TrnR2/GDNFR-beta/NTNR-alpha/RETL2). Here, we studied the effect of GDNF
      and NTN on human neuroblastomas in the short-term primary culture system, as well
      as the expression of c-Ret, GFR alpha-1, GFR alpha-2, GDNF, and NTN. GDNF (1-100
      ng/ml) induced morphological differentiation in 34 of 38 primary neuroblastomas
      and an accompanying increase in c-Fos induction. These effects were markedly
      enhanced by treatment with 5 microM all-trans-retinoic acid. Although GDNF alone
      induced a rather weak differentiation independent of the disease stages, the
      enhancement of neurite outgrowth induced by treatment with both GDNF and all
      trans-retinoic acid was significantly correlated with younger age (less than 1
      year; P = 0.0039), non-stage 4 diseases (P = 0.0023), a single copy of N-myc (P =
      0.027), and high levels of TRK-A expression (P = 0.0062). To examine the
      expression levels of GFR alpha-1, we cloned a short form of the human GFR alpha-1
      gene with a 15-bp deletion by screening a human adult substantia nigra cDNA
      library. Many primary neuroblastomas expressed c-Ret, GFR alpha-1, and GFR alpha
      2 as well as their ligands, GDNF and NTN, suggesting the presence of a paracrine
      or autocrine signaling system within the tumor tissue. The effect of NTN on
      primary culture cells of neuroblastoma was similar to that of GDNF. These imply
      that the GDNF(NTN)/c-Ret/GFR alpha-1(GFR alpha-2) signaling may have an important
      role in regulating the growth, differentiation, and cell death of neuroblastomas.

PMID- 9605761
TI  - Allelic loss of 16q23.2-24.2 is an independent marker of good prognosis in
      primary breast cancer.
AB  - Allelic loss, detected as a loss of heterozygosity (LOH) on the long arm of
      chromosome 16, is an early and frequent event in breast cancer. Despite this, the
      clinical significance of LOH on 16q has been very poorly studied. In this study,
      corresponding blood and tumor samples from 199 clinically well-characterized
      primary breast cancer patients were analyzed for LOH with the highly polymorphic
      microsatellite marker D16S511, located at 16q23.2-24.2. 61% of 168 informative
      tumors showed LOH. Univariate and multivariate analysis found a highly
      significant association between LOH at 16q23.2-24.2 and freedom from distant
      metastases, disease-free survival, and overall survival, respectively. No
      association was found with other clinical parameters such as menopausal status,
      tumor size, lymph node status, histopathology, and lymph node capsule invasion.
      This makes allelic loss of 16q23.2-24.2 an independent marker of good prognosis
      for primary breast cancer.

PMID- 9605762
TI  - Chromosomal gains and losses in primary cutaneous melanomas detected by
      comparative genomic hybridization.
AB  - The analysis of genetic changes in primary cutaneous melanoma has been limited by
      the need for fixation for diagnostic purposes. However, comparative genomic
      hybridization is able to analyze such specimens. We have applied comparative
      genomic hybridization to 32 primary melanomas to discover and map genomic regions
      with aberrant DNA copy numbers. The analysis was performed on native,
      nonamplified DNA extracted from manually dissected tumor sections. Loss of
      chromosome 9 was detected in 81% of the tumors, most commonly affecting the p
      arm. Additional common losses occurred on chromosomes 10 (63%), 6q (28%), and 8p
      (22%). Gains in copy number involved chromosomes 7 (50%), 8 (34%), 6p (28%), 1q
      (25%), 20 (13%), 17 (13%), and 2 (13%). Amplifications indicating areas harboring
      potential oncogenes were seen at 4q12, 5p14.3-pter, 7q33-qter, 8q12-13, 11q13.3
      14.2, and 17q25. Correlations among the regions with copy number changes indicate
      that losses of chromosomes 9 and 10 occur early on in melanoma progression,
      whereas gains of chromosome 7 occur later. This sequence of events was further
      substantiated by an intratumoral comparison of copy number changes in areas with
      radial and vertical growth phase patterns. The overall pattern of regions
      affected by copy number changes is consistent with cytogenetic data from
      metastatic melanoma; however, the frequencies of involvement differ, providing
      further insight into the course of genetic events.

PMID- 9605763
TI  - Increased translocations and aneusomy in chromosomes 8 and 21 among workers
      exposed to benzene.
AB  - Chromosome aberrations in peripheral blood lymphocytes have been used for many
      years to monitor human populations exposed to potential carcinogens. Recent
      reports have confirmed the validity of this approach by demonstrating that
      elevated levels of chromosome aberrations in lymphocytes are associated with
      subsequent increased cancer risk, especially for increased mortality from
      hematological malignancies including acute myeloid leukemia (AML). We postulated
      that this approach could be improved in two ways: (a) by detecting oncogenic
      disease-specific aberrations; and (b) by using chromosome painting so that many
      more metaphases could be analyzed. Numerical and structural aberrations in
      chromosomes 8 and 21 are commonly observed in AML. In the present study, we
      painted chromosomes 8 and 21 in lymphocyte metaphases from 43 healthy workers
      exposed to benzene, an established cause of AML, and from 44 matched controls. To
      examine dose-response relationships the workers were divided into two groups at
      the median exposure level, a lower-exposed group (< or = 31 ppm; n = 21), and a
      higher-exposed group (> 31 ppm; n = 22). Benzene exposure was associated with
      significant increases in hyperdiploidy of chromosomes 8 (1.2, 1.5, and 2.4 per
      100 metaphases; P < 0.0001) and 21 (0.9, 1.1, and 1.9 per 100 metaphases; P <
      0.0001). Translocations between chromosomes 8 and 21 were increased up to 15-fold
      in highly exposed workers (0.01, 0.04, and 0.16 per 100 metaphases; P < 0.0001).
      In one highly exposed individual, these translocations were reciprocal and were
      detectable by reverse transcriptase-PCR. These data indicate a potential role for
      t(8;21) in benzene-induced leukemogenesis and are consistent with the hypothesis
      that detection of specific chromosome aberrations may be a powerful approach to
      identify populations at increased risk of leukemia.

PMID- 9605764
TI  - Cap43, a novel gene specifically induced by Ni2+ compounds.
AB  - To better understand the molecular mechanism(s) involved in the essentiality,
      toxicity, and/or carcinogenicity of nickel compounds, a mRNA differential display
      technique was used to identify gene(s) that were specifically induced by these
      carcinogens. Differential expression of several genes was observed in human lung
      A549 cells exposed to nickel subsulfide. One gene, Cap43, which expressed a 3.0
      kb mRNA encoding a Mr 43,000 protein, was found to be induced within 4-6 h by
      either Ni3S2 or NiCl2 in A549 cells and attained a level as high as 30-fold
      within 24-36 h of treatment. Twelve other tested metal compounds failed to induce
      Cap43 expression, leading to the conclusion that, with regard to metals, the
      induction of this gene was nickel-specific. Oxidative stress that is often caused
      by metals and heat shock did not induce Cap43 further, suggesting a specific
      nature in the signaling pathway involved in Cap43 induction. Activation of
      signaling pathways with vanadate did not induce Cap43 nor did trifluoperazine
      block its induction by nickel; however, okadaic acid, a serine/threonine
      phosphatase inhibitor, induced Cap43 to a greater extent than any nickel compound
      tested. Homocysteine did not induce Cap43 in a number of cell lines, with the
      exception of human endothelial cells. The Cap43 gene was found to be induced by
      nickel not only in all tested human and rodent cell lines in vitro but also in
      several rat organs after oral exposure to NiCl2. We have found that the primary
      signal for Cap43 induction was an elevation of free intracellular Ca2+ caused by
      Ni2+ exposure because Cap43 was induced by calcium ionophores and its induction
      was attenuated by bis-(O-aminophenyl)-ethane-N,N,N',N'-tetraacetic acid
      tetra(acetoxymethyl)-ester, a chelator of intracellular Ca2+. We found that the
      Cap43 gene was evolutionarily conserved and similarly regulated in humans, mice,
      and rats. Recent studies have shown that Cap43 is expressed at lower levels in
      colon cancer. Further studies of Cap43 regulation by Ca2+ should enhance our
      understanding of the role of Cap43 in cell function and cancer pathogenesis.

PMID- 9605765
TI  - Germ-line-derived hinge domain p53 mutants have lost apoptotic but not cell cycle
      arrest functions.
AB  - The protein p53 is a critical tumor suppressor, as demonstrated by its frequent
      mutation in human cancers. Overexpression of the wild-type form of the p53 tumor
      suppressor gene in human cancer cell lines has been shown to lead to either cell
      cycle arrest or apoptosis. A study of two Li-Fraumeni syndrome-derived p53 hinge
      domain mutants shows that both mutants retain the ability to arrest cell growth
      but are significantly impaired for the induction of apoptosis in human p53-null
      cell lines. This indicates that the hinge domain may be important in the
      regulation of p53-dependent apoptosis.

PMID- 9605766
TI  - Cloning, characterization, and chromosomal localization of a gene frequently
      deleted in human liver cancer (DLC-1) homologous to rat RhoGAP.
AB  - The isolation of genes involved in cancer development is critical for uncovering
      the molecular basis of cancer. We report here the isolation of the full-length
      cDNA and chromosomal localization of a new gene frequently deleted in liver
      cancer (DLC-1) that was identified by representational difference analysis. Loss
      of heterozygosity was detected for DLC-1 in 7 of 16 primary hepatocellular
      carcinomas (HCCs) and in 10 of 11 HCC cell lines. Although mRNA for DLC-1 was
      expressed in all normal human tissues, it was not expressed in 4 of 14 HCC cell
      lines. Full-length cDNA for DLC-1 of 3800 bp encodes a protein of 1091 amino
      acids, has 86% homology with rat p122 RhoGAP gene, and was localized by
      fluorescence in situ hybridization on chromosome 8 at bands p21.3-22. Deletions
      on the short arm of chromosome 8 are recurrent in liver, breast, lung, and
      prostate cancers, suggesting the presence of tumor suppressor genes. DLC-1 may be
      a tumor suppressor gene in liver cancer as well as in other cancers.

PMID- 9605767
TI  - Normal keratinocytes suppress early stages of neoplastic progression in
      stratified epithelium.
AB  - The importance of interactions between potentially neoplastic cells and their
      normal neighbors on malignant progression of precancerous lesions is not well
      understood. In this study, we have established novel human tissue models that
      simulate intraepithelial neoplasia in stratified epithelia to investigate the
      fate and phenotype of neoplastic keratinocyte clones in normal cell context
      during clonal expansion and early malignant progression. This was accomplished by
      mixing genetically marked keratinocytes with malignant potential (II-4) with
      normal keratinocytes at ratios of 1:1, 4:1, 12:1, and 64:1 (normal:II-4) to
      visualize nests of marked, dysplastic cells in organotypic cultures and in
      cultures transplanted to nude mice. Four weeks after transplantation of 4:1
      mixtures, grafts were normal and demonstrated no beta-galactosidase (beta-gal)
      positive cells, suggesting that cells with malignant potential were eliminated
      from the tissue at this mixing ratio. However, grafted 1:1 mixtures demonstrated
      persistence of expanded foci of dysplastic cells (4 weeks) and invasion (8
      weeks). This demonstrated that the capacity of a keratinocyte clone with
      neoplastic potential to persist and invade is directly related to the threshold
      number of such keratinocytes present in the tissue. To explain the failure of II
      4 to persist in vivo, the intraepithelial dynamics between the two populations
      were studied before grafting. Double-stain immunofluorescence for
      bromodeoxyuridine/beta-gal and filaggrin/beta-gal of mixtures grown in
      organotypic cultures for 7 days demonstrated that when increasing numbers of
      normal cells were added (12:1), II-4 ceased to proliferate and expressed
      filaggrin. This suggests a novel mechanism of tumor suppression wherein contact
      with normal cells induces cell cycle withdrawal and terminal differentiation of
      potentially malignant cells. These findings support the view that normal tissue
      architecture acts as a dominant suppressor of early neoplastic progression in
      stratified epithelium.

PMID- 9605768
TI  - Matrix metalloproteinases-2 and -9 are expressed in human neuroblastoma:
      contribution of stromal cells to their production and correlation with
      metastasis.
AB  - Neuroblastoma, the second most common solid childhood tumor, can be a highly
      invasive and metastatic form of cancer. To assess the role of matrix-degrading
      proteases in this cancer, we have examined the expression of matrix
      metalloproteinases (MMPs) and their corresponding tissue inhibitors of
      metalloproteinases (TIMPs) in 7 human neuroblastoma cell lines and 24 primary
      untreated tumors. MMP-2 (gelatinase A) and MMP-9 (gelatinase B) were the only two
      MMPs expressed. MMP-2 was detected predominantly in an inactive proform in all
      tumor cell lines and tumor tissue extracts. The lack of MMP-2 activation in cell
      lines was attributed to the absence of expression of a membrane-type MMP (MT1
      MMP), which activates proMMP-2, and to the abundant expression of TIMPs,
      particularly TIMP-2. Immunohistochemical analysis of tumor tissue samples
      indicated that MMP-2 was present in both tumor cells and stromal cells. In
      contrast, MMP-9 was not expressed by neuroblastoma cell lines but was present in
      inactive and active forms in extracts from tumor tissues. Immunohistochemical
      analysis of positive specimens indicated that MMP-9 was predominantly present in
      stromal, vascular, and perivascular cells surrounding nests of tumor cells. There
      was no correlation between the levels of these MMPs and the MYCN copy number or
      the histopathological phenotype. However, there were higher levels of MMP-2 and
      MMP-9 in stage IV (metastatic) disease when compared with stages I and II
      (noninvasive and nonmetastatic) or IV-S (P < 0.05).

PMID- 9605769
TI  - The role of type I and type II tumor necrosis factor (TNF) receptors in the
      ability of TNF-alpha to transduce a proliferative signal in the human
      megakaryoblastic leukemic cell line Mo7e.
AB  - We investigated the effects of tumor necrosis factor (TNF) alpha on the human
      megakaryocytic leukemic cell lines Mo7e, Meg-01, and Dami/HEL. Our data show that
      both type I and type II TNF receptors (TNF-RI and TNF-RII) are expressed on all
      of these cells, and TNF-alpha significantly stimulates the proliferation of
      growth factor-dependent Mo7e cells but not of Meg-01 or Dami/HEL cells, which
      grow in a factor-independent manner. TNF-alpha serves predominantly as a mitogen
      for Mo7e cell proliferation and does not induce Mo7e cell differentiation.
      Coincubation with both TNF-alpha and anti-TNF-alpha neutralizing antibody
      completely abolishes the TNF-alpha-induced proliferation of Mo7e cells. In
      bioassays, there is no detectable level of other stimulatory cytokines in
      conditioned medium from Mo7e cells previously stimulated by TNF-alpha, implying
      that the stimulatory effect of TNF-alpha on Mo7e cells is derived from the direct
      action of TNF-alpha rather than via the induction of secondary cytokines by TNF
      alpha. Flow cytometric studies demonstrated that TNF-alpha binds to Mo7e cells
      that have been pretreated with either anti-TNF-RI or anti-TNF-RII neutralizing
      antibody, but TNF-alpha does not bind to cells pre-exposed to both receptor
      antibodies. However, the incubation of Mo7e cells with either TNF-RI or TNF-RII
      neutralizing antibodies or with either soluble TNF-RI or TNF-RII inhibits TNF
      alpha-induced cell proliferation, indicating the requirement of interactions with
      both TNF receptors for the mitogenic activity of TNF-alpha. Furthermore, our data
      suggest that an alternative signaling pathway may be involved in TNF-alpha
      induced Mo7e cell proliferation, because the common mitogen-activated protein
      kinase (MAPK) and signal transducer and activator of transcription (STAT)
      signaling pathways activated by other cytokines that induce Mo7e cell
      proliferation are not activated by TNF-alpha.

PMID- 9605770
TI  - Downstream events in mammary gland morphogenesis mediated by reexpression of the
      alpha2beta1 integrin: the role of the alpha6 and beta4 integrin subunits.
AB  - Our previous studies demonstrated that reexpression of the alpha2beta1 integrin
      by a poorly differentiated breast carcinoma cell line, Mm5MT, resulted in
      dramatic reversion of a malignant phenotype to a differentiated epithelial
      phenotype. We hypothesized that reexpression of the alpha2beta1 integrin may
      regulate expression of other genes, the expression of which contributed to the
      dramatic phenotypic change. We now show that reexpression of the alpha2beta1
      integrin results in up-regulation of both the alpha6 and beta4 integrin subunits
      but no change in the alpha1, alpha3, alpha5, or beta1 integrin subunits or E
      cadherin. To further investigate the role of the alpha6 and beta4 integrin
      subunits in mediating the phenotypic changes elicited by reexpression of the
      alpha2beta1 integrin, the alpha6 or beta4 integrin subunit was expressed in our
      Mm5MT model. Expression of either subunit increased adhesion to laminin-1.
      Although adhesion to collagen was unaltered, contraction of three-dimensional
      collagen gels was reduced. Expression of either the alpha6 or beta4 integrin
      subunit also restored some aspects of a less malignant phenotype, including the
      acquisition of contact inhibition and diminution of anchorage-dependent and
      anchorage-independent growth rates. The alpha6 and beta4 transfectants formed
      three-dimensional organized structures when grown in gels of reconstituted
      basement membrane but did not form the highly branched, duct-like structures
      formed by the alpha2 transfectants. In contrast to the reduced invasiveness of
      the alpha2 transfectants, the alpha6 and beta4 transfectants retained an invasive
      phenotype. These results suggest that expression of the alpha6beta4 integrin
      contributes to some but not all of the phenotypic changes elicited by
      reexpression of the alpha2 integrin subunit and modulates the function of other
      integrins on these cells. Using our Mm5MT model, we are defining the cascade of
      integrin expression required for maintenance of the differentiated mammary
      epithelial cell phenotype.

PMID- 9605771
TI  - Expression of urokinase-type plasminogen activator (u-PA), u-PA receptor, and
      tissue-type PA messenger RNAs in human hepatocellular carcinoma.
AB  - Expression of plasminogen activators (PAs) and urokinase-type PA receptor (u-PAR)
      is associated with tumor growth and invasion. For in vivo human tumor tissues,
      there is no information on gene expression of PAs in hepatocellular carcinoma
      (HCC) or other hepatic pathophysiological conditions. In this study we examined
      the relative levels of u-PA, tissue-type PA (t-PA), and u-PAR mRNA expression in
      human HCC by reverse transcription-PCR compared with those expressed in
      peritumoral hepatic tissues. Twenty-five of 25 HCCs expressed u-PA mRNA, as well
      as 16 of 25 hepatic peritumoral tissues. However, none of the 14 cases of
      nontumorous liver samples (i.e., normal parenchyma, steatosis, and nonspecific
      reactive and chronic hepatitis) showed detectable levels of u-PA mRNA. The same
      samples analyzed for uPAR and t-PA mRNAs exhibited higher levels of these mRNAs
      in the malignant tissues compared with nontumorous ones. A strong correlation was
      found between the relative levels of u-PA and t-PA mRNAs detected in the tumor
      and in the corresponding peritumoral tissues (P < 0.001 for u-PA; P < 0.02 for t
      PA). However, there was no correlation between the expression of u-PA and t-PA in
      HCC (P = 0.565). Furthermore, a significant inverse correlation was found between
      survival months of male patients and the relative level of u-PA mRNA (P < 0.05)
      detected at the time of biopsy, whereas no correlation was found in the case of t
      PA mRNA. These results are in line with the possible differential biological role
      of u-PA and t-PA in the tumor etiopathogenesis and suggest that the detection of
      relative levels of u-PA mRNA may be a useful prognostic factor for male HCC
      patients.

PMID- 9605772
TI  - Transformation of epithelial Madin-Darby canine kidney cells with p60(v-src)
      induces expression of membrane-type 1 matrix metalloproteinase and invasiveness.
AB  - Membrane-type 1 matrix metalloproteinase (MT1-MMP) is expressed both in carcinoma
      cells and in surrounding stromal fibroblasts. MT1-MMP localizes to the surface of
      tumor cells and is thought to play an important role in tumor invasion. To
      analyze the mechanism of MT1-MMP gene expression in epithelial tumor cells, the
      dog kidney epithelial cell line Madin-Darby canine kidney (MDCK) was transformed
      by oncogenes, including v-src, and expression of MT1-MMP was examined.
      Transformation of MDCK cells with v-src resulted in loss of cell-to-cell contacts
      and morphological change. Expression of MT1-MMP in v-src-transformed cells was
      identified by Northern and Western blotting. Gelatin zymography analysis showed
      that progelatinase A in the culture medium was processed from latent to activated
      form by MDCK cells transformed with v-src. The MDCK cells transformed by v-src
      were tumorigenic in the subcutis (ectopic) and kidney (orthotopic) of nude mice
      and spontaneously metastasized to the lung after orthotopic implantation. These
      results suggest that MT1-MMP induced by v-src transformation may promote
      invasiveness of transformed cells.

PMID- 9605773
TI  - Expression of ribonucleotide reductase after ionizing radiation in human cervical
      carcinoma cells.
AB  - Ribonucleotide reductase (RR), the rate-limiting enzyme in the de novo synthesis
      of deoxynucleotide triphosphates (dNTPs), is a potential target for cancer
      therapy. We characterized the response of RR in a human cervical carcinoma cell
      line, Caski, after damage by ionizing radiation (IR). We also investigated the
      cell cycle regulation of both the regulatory (R1) and catalytic (R2) RR subunits
      in an attempt to distinguish between a direct DNA damage induction of RR by IR
      and a cell cycle-dependent expression of RR after IR. Confluent, growth-arrested
      Caski cells showed a > or = 5-fold increase in R2 mRNA and an 18-fold increase in
      R2 protein as cells entered S phase after serum stimulation. The R2 protein
      levels peaked in late S phase and returned to lower basal levels in G2-M. No
      changes in R1 mRNA and protein levels occurred with progression through the cell
      cycle after serum stimulation. In growth-arrested Caski cells treated with IR (6
      Gy) without serum stimulation, a similar rise (17-fold) in R2 protein was evident
      at 24 h after IR and was associated with a 4-fold increase in in situ RR enzyme
      activity, but no increases in R1 and R2 mRNA nor R1 protein were found. E2
      promoter binding factor 1 mRNA and protein levels also showed no change after IR.
      Growth-arrested controls (no IR and no serum stimulation) showed <4-fold
      elevation in R2 protein. These data suggest that RR plays a role in IR-mediated
      damage responses in Caski cells, which appears different than RR regulation after
      a proliferation (serum) stimulus. Such a response to IR in human tumor cells has
      not been reported previously. The use of specific R2 protein or RR enzyme
      inhibitors after IR may enhance IR cytotoxicity by altering this potential RR
      mediated repair pathway.

PMID- 9605775
TI  - 12-O-tetradecanoylphorbol-13-acetate-induced apoptosis in LNCaP cells is mediated
      through ceramide synthase.
AB  - Protein kinase C (PKC) activation is often antiapoptotic, although in a few cell
      types PKC initiates apoptosis by an unknown mechanism. Recent investigations
      showed that activation of PKC alpha by 12-O-tetradecanoylphorbol 13-acetate (TPA)
      induced apoptosis in LNCaP prostate cancer cells. The present studies examine the
      mechanism of this effect and show that de novo ceramide generation through the
      enzyme ceramide synthase is required. TPA induced rapid ceramide generation,
      which was detectable by 1 h and increased linearly for 12 h. TPA-induced
      apoptosis was measurable by 12 h and was progressive for 48 h. Investigations
      into the mechanism of TPA-induced ceramide generation revealed that acid and
      neutral sphingomyelinase activities were not enhanced. However, TPA induced an
      increase in ceramide synthase activity that persisted for at least 16 h.
      Treatment with fumonisin B1, a specific natural inhibitor of ceramide synthase,
      abrogated both ceramide production and TPA-induced apoptosis. Ceramide analogues
      bypassed fumonisin B1 inhibition to initiate apoptosis directly. Thus, ceramide
      appears to be a necessary signal for TPA-induced apoptosis in LNCaP cells. This
      represents the first description of a pathway by which PKC may signal apoptosis.

PMID- 9605774
TI  - Activation of the ras-mitogen-activated protein kinase pathway and
      phosphorylation of ets-2 at position threonine 72 in human ovarian cancer cell
      lines.
AB  - The activation status of the ras pathway was studied in eight ovarian tumor cell
      lines. Three biochemical parameters indicative of ras activation were tested: (a)
      the ratio of the ras-GTP:ras-GDP complex; (b) the activity of mitogen-activated
      protein kinases p42/p44; and (c) ets-2 phosphorylation at position threonine 72,
      a mitogen-activated protein kinase phosphorylation site in vivo. Four of the
      ovarian tumor cell lines had an activated ras pathway by these three parameters,
      whereas only one of these contained a mutated ras gene. In addition, ras/ets-2
      responsive genes such as the urokinase plasminogen activator (uPA) were activated
      in these four cell lines. Transient transfection assays indicated that the
      compound ets-AP1 oncogene responsive enhancer present in the uPA gene was the
      target of ras signaling in ovarian tumor cells and that the combination of
      activated ras and ets-2 could superactivate the uPA enhancer element.
      Coexpression of the dominant-negative ras-Asn17 cDNA gene abrogated activity of
      this uPA element in ovarian tumor cells. These data indicate that ets-2 is a
      nuclear target of ras action in ovarian tumor cell lines and that ras signaling
      pathways may be activated in ovarian cancer by mechanisms independent of direct
      genetic damage to ras genes.

PMID- 9605776
TI  - Accepting limits.

PMID- 9605777
TI  - Effects of a home-based intervention among patients with congestive heart failure
      discharged from acute hospital care.
AB  - BACKGROUND: We examined the effect of a home-based intervention (HBI) on
      readmission and death among "high-risk" patients with congestive heart failure
      discharged home from acute hospital care. METHODS: Hospitalized patients with
      congestive heart failure and impaired systolic function, intolerance to exercise,
      and a history of 1 or more hospital admissions for acute heart failure were
      randomized to either usual care (n=48) or HBI at 1 week after discharge (n=49).
      Home-based intervention comprised a single home visit (by a nurse and pharmacist)
      to optimize medication management, identify early clinical deterioration, and
      intensify medical follow-up and caregiver vigilance as appropriate. The primary
      end point of the study was frequency of unplanned readmissions plus out-of
      hospital deaths within 6 months of discharge. Secondary end points included
      duration of hospital stay and overall mortality. RESULTS: During follow-up,
      patients in the HBI group had fewer unplanned readmissions (36 vs 63; P=.03) and
      fewer out-of-hospital deaths (1 vs 5; P=.11): 0.8+/-0.9 vs 1.4+/-1.8 (mean +/-
      SD) events per patient assigned to HBI and usual care, respectively (P=.03).
      Patients in the HBI group also had fewer days of hospitalization (261 vs 452;
      P=.05) and fewer total deaths (6 vs 12; P=.11). Patients assigned to usual care
      were more likely to experience 3 or more readmissions for acute heart failure
      (P=.02). Predictors of unplanned readmission were (1) 14 days or more of
      unplanned readmission during the 6 months before study entry (odds ratio [OR],
      5.2; 95% confidence interval [CI], 1.8-16.2), (2) previous admission for acute
      myocardial ischemia (OR, 3.3; 95% CI, 1.2-9.1), and (3) an albumin plasma
      concentration of 38 g/L or less (OR, 2.4; 95% CI, 1.2-6.0). Home-based
      intervention was also associated with a trend toward reduced risk of unplanned
      readmission (OR, 0.4; 95% CI, 0.2-1.1). CONCLUSION: Among a cohort of high-risk
      patients with congestive heart failure, HBI was associated with reduced frequency
      of unplanned readmissions plus out-of-hospital deaths within 6 months of
      discharge from the hospital.

PMID- 9605778
TI  - Temporal patterns in the medical treatment of congestive heart failure with
      angiotensin-converting enzyme inhibitors in older adults, 1989 through 1995.
AB  - BACKGROUND: Evidence from clinical trials in the past decade has consistently
      shown that angiotensin-converting enzyme (ACE) inhibitors reduce morbidity and
      mortality in patients with congestive heart failure (CHF). The extent to which
      clinical practice has adopted ACE inhibitor therapy is unknown. METHODS: The
      Cardiovascular Health Study is a prospective observational study of 5201
      community-dwelling adults aged 65 years and older. Prevalent CHF cases were
      identified on study entry (from June 10, 1989, through May 31, 1990) and incident
      CHF cases were identified throughout 5 years of follow-up. Medication data were
      collected from annual medication inventories. The percentage of patients with CHF
      using ACE inhibitors was calculated at each annual examination. Temporal trends
      in CHF treatment with ACE inhibitors between June 10, 1989, through May 31, 1990,
      and June 1, 1994, through May 31, 1995, were analyzed. RESULTS: Use of ACE
      inhibitors to treat CHF increased slightly over time among prevalent cases at
      each annual examination: 26% of prevalent CHF cases were treated in 1989-1990
      compared with 36% of prevalent cases in 1994-1995. This 10% increase was
      statistically significant (P<.01). Participants with low ejection fractions were
      2 times more likely to be treated with ACE inhibitors than were those with normal
      ejection fraction and this tendency did not change over time. Among cases newly
      diagnosed in the year before the 1990-1991 examination, 42% were using ACE
      inhibitors; among those newly diagnosed in the year before 1994-1995, 40% were
      using ACE inhibitors. This 2% decrease was not statistically significant (P=.68).
      CONCLUSION: These findings suggest that, while the medical management of CHF with
      ACE inhibitors has increased modestly over time in prevalent cases, these drugs
      may still be underused, especially among incident cases.

PMID- 9605779
TI  - Outcomes of acute exacerbation of severe congestive heart failure: quality of
      life, resource use, and survival. SUPPORT Investigators. The Study to Understand
      Prognosis and Preferences for Outcomes and Risks of Treatments.
AB  - BACKGROUND: Congestive heart failure (CHF) is a common disease with high health
      care costs and high mortality rates. Knowledge of the health-related quality of
      life outcomes of CHF may guide decision making and be useful in assessing new
      therapies for this population. METHODS: A prospective cohort study was conducted
      involving 1390 adult patients hospitalized with an acute exacerbation of severe
      CHF (New York Heart Association class III-IV). Demographic data and health
      related quality of life were determined by interview; physiologic status and cost
      and intensity of care were determined from hospital charts. RESULTS: The median
      (25th, 75th percentiles) age of patients was 68.0 (58.2, 76.9) years; 61.7% were
      male. Survival was 93.4% at discharge from the index hospitalization, 72.9% at
      180 days, and 61.5% at 1 year. Of patients interviewed at 180 days, the median
      health rating on a scale of 0 to 100 (0 indicates death; 100, excellent health)
      was 60 (interquartile range, 50-80), and 59.7% were independent in their
      activities of daily living. Overall quality of life was reported to be good, very
      good, or excellent in 58.2% at 180 days. Patients with worse functional capacity
      were more likely to die. Health perceptions among the patients with available
      interview data improved at 60 and 180 days after acute exacerbation of severe
      CHF. CONCLUSIONS: Patients hospitalized for acute exacerbation of severe CHF have
      a generally poor 6-month survival, but survivors retain relatively good
      functional status and have good health perceptions. Furthermore, health
      perceptions improve after the acute exacerbation.

PMID- 9605780
TI  - Communicating do-not-resuscitate orders with a computer-based system.
AB  - BACKGROUND: Do-not-resuscitate (DNR) orders for critically ill patients are
      frequently miscommunicated between attending physicians, house staff, and nurses.
      A computer-based system was developed to improve the communication of a procedure
      specific DNR order form. METHODS: Concordance of understanding of patients' DNR
      status was measured with the use of unstructured DNR orders (period 1), procedure
      specific DNR order forms (period 2), and procedure-specific DNR order forms
      administered with a computer-based communication system (period 3). The 3
      components of the DNR order assessed were (1) the clinical events to which the
      DNR order applied, (2) whether the DNR order withheld all elements of
      cardiopulmonary resuscitation, and (3) whether other treatments were to be
      withheld. RESULTS: For the 147 patients, the computer-based system in period 3 (n
      = 71) improved concordance for attending physicians and nurses or residents for
      all 3 of the DNR components compared with period 1 (n = 40) and some of the DNR
      components compared with period 2 (n = 36). Concordance was "substantial" or
      "almost perfect" as measured by the K statistic during period 3. The proportion
      of agreement for the composite of all 3 components of the DNR order increased
      during each period (P<.001, period 3 vs period 1). Overall agreement between all
      caregivers for the composite DNR order also improved from period 1 (22.2%) to
      period 2 (47.8%) and period 3 (61.9%; P<.001 vs period 1). Errors in order entry
      were detected by physicians because of the computer system and corrected in 9.9%
      of DNR orders in period 3. Progress note documentation of DNR status did not
      improve during period 3. The procedures of period 3 were considered acceptable by
      the physician and nursing staff. CONCLUSION: A computer-based system combined
      with a procedure-specific DNR order form improves communication of patients' DNR
      status in a critical care setting.

PMID- 9605781
TI  - Clinical correlates of insomnia in patients with chronic illness.
AB  - BACKGROUND: Patients with chronic insomnia are more likely to develop affective
      disorders, cardiac morbidity, and other adverse health outcomes, yet many
      clinicians tend to trivialize the complaint of insomnia or to attribute it only
      to psychiatric causes. OBJECTIVES: To estimate the prevalence and longitudinal
      course of insomnia in patients with documented chronic medical illness and/or
      depression and to quantify the associations between specific chronic conditions
      and insomnia. METHODS: The presence of mild or severe insomnia was based on
      responses to a sleep questionnaire completed by 3445 patients with at least 1 of
      5 physician-identified chronic conditions (hypertension, diabetes, congestive
      heart failure, myocardial infarction, or depression) at baseline; a subsample of
      1814 patients completed follow-up questionnaires at 2 years. Using multivariate
      techniques, we evaluated the relationship between chronic conditions, patient
      reported comorbidities, and insomnia (complaints of initiating and maintaining
      sleep), adjusting for sociodemographics and health habits. RESULTS: Sixteen
      percent of study patients had severe and 34% had mild insomnia at baseline. At 2
      year follow-up, 59% (95% confidence interval, 55%-63%) of patients with mild
      insomnia and 83% (95% confidence interval, 78%-88%) of patients with severe
      insomnia at baseline still had sleep problems. Odds ratios corresponding to mild
      and severe insomnia for key risk factors were as follows: current depressive
      disorder, 2.6 and 8.2; subthreshold depression, 2.2 and 3.4; congestive heart
      failure, 1.6 and 2.5; obstructive airway disease, 1.6 and 1.5; back problems, 1.4
      and 1.5; hip impairment, 2.2 and 2.7; and prostate problems, 1.6 and 1.4. The
      majority of insomnia-comorbidity associations observed at baseline persisted at 2
      year follow-up. CONCLUSIONS: Patients with insomnia require follow-up, as the
      majority continue to be bothered by difficulty initiating and maintaining sleep.
      In addition to detecting affective disorders in patients with insomnia,
      clinicians should focus on medical conditions that disturb sleep, especially
      cardiopulmonary disease, painful musculoskeletal conditions, and prostate
      problems.

PMID- 9605782
TI  - NSAIDs associated with increased risk of congestive heart failure in elderly
      patients taking diuretics.
AB  - BACKGROUND: Both diuretics and nonsteroidal anti-inflammatory drugs (NSAIDs) are
      widely used, in particular among the elderly. The use of NSAIDs may decrease the
      efficacy of diuretics and induce congestive heart failure (CHF) in patients
      treated with diuretics. OBJECTIVE: To investigate the risk of CHF associated with
      combined use of diuretics and NSAIDs in patients older than 55 years. METHODS: We
      conducted a study in a base cohort of 10,519 recipients of diuretics and NSAIDs
      identified in the PHARMO database during the period from 1986 through 1992. The
      incidence density of hospitalizations for CHF during exposure to both diuretics
      and NSAIDs (index) was compared with that during exposure to diuretics only
      (reference). RESULTS: We found an overall increased risk of hospitalization for
      CHF during periods of concomitant use of diuretics and NSAIDs compared with use
      of diuretics only (crude relative risk, 2.2; 95% confidence interval, 1.7-2.9).
      After adjusting for cofactors including age, sex, history of hospitalization, and
      drug use, a 2-fold increased risk remained (relative risk, 1.8; 95% confidence
      interval, 1.4-2.4). CONCLUSION: Use of NSAIDs in elderly patients taking
      diuretics is associated with a 2-fold increased risk of hospitalization for CHF,
      especially in those with existing serious CHF.

PMID- 9605783
TI  - Elderly patients receive less aggressive medical and invasive management of
      unstable angina: potential impact of practice guidelines.
AB  - BACKGROUND: The Agency for Health Care Policy and Research (AHCPR) released a
      practice guideline on the diagnosis and management of unstable angina in 1994.
      OBJECTIVE: To examine practice variation across the age spectrum in the
      management of patients hospitalized with unstable angina 2 years before release
      of the AHCPR guideline. DESIGN: Retrospective cohort. SETTING: Urban academic
      hospital. PATIENTS: All nonreferral patients diagnosed as having unstable angina
      who were hospitalized directly from the emergency department to the intensive
      care or telemetry unit between October 1, 1991, and September 30, 1992.
      MEASUREMENTS: Percentage of eligible patients receiving medical treatment
      concordant with 8 important AHCPR guideline recommendations. RESULTS: Half of the
      280 patients were older than 66 years; women were older than men on average (70
      vs 64 years; P<.001). After excluding those with contraindications to therapy,
      patients in the oldest quartile (age, 75.20-93.37 years) were less likely than
      younger patients to receive aspirin (P<.009), beta-blockers (P<.04), and referral
      for cardiac catheterization (P<.001). Overall guideline concordance weighted for
      the number of eligible patients declined with increasing age (87.4%, 87.4%,
      84.0%, and 74.9% for age quartiles 1 to 4, respectively; chi2, P<.001).
      Increasing age, the presence of congestive heart failure at presentation, a
      history of congestive heart failure, previous myocardial infarction, increasing
      comorbidity, and elevated creatinine concentration were associated with care that
      was less concordant with AHCPR guideline recommendations; only age and congestive
      heart failure at presentation remained significant in the multivariate analysis
      (odds ratios, 1.28 per decade [95% confidence interval, 1.02-1.61] and 3.16 [95%
      confidence interval, 1.57-6.36], respectively). CONCLUSIONS: Older patients were
      less likely to receive standard therapies for unstable angina before release of
      the 1994 AHCPR guideline. Patients presenting with congestive heart failure also
      received care that was more discordant with guideline recommendations. The AHCPR
      guideline allows identification of patients who receive nonstandard care and, if
      applied to those patients with the greatest likelihood to benefit, could lead to
      improved health care delivery.

PMID- 9605784
TI  - A foodborne outbreak of Cyclospora cayetanensis at a wedding: clinical features
      and risk factors for illness.
AB  - BACKGROUND: Cyclospora cayetanensis, a coccidian parasite, has increasingly been
      recognized as a cause of gastrointestinal tract illness. We describe an outbreak
      of Cyclospora infection following a wedding reception. OBJECTIVES: To investigate
      and characterize risk factors associated with the outbreak of Cyclospora and to
      describe the observed clinical course and spectrum of illness. METHODS:
      Retrospective cohort study involving 94 of the 101 guests who attended a wedding
      reception at a restaurant in Boston, Mass. RESULTS: Fifty-seven respondents met
      the case definition of infection; 12 of these had laboratory-confirmed
      Cyclospora. The epidemic curve was consistent with a point source outbreak with a
      median incubation period of 7 days. Commonly reported symptoms included diarrhea
      (100%), weight loss (93%), fatigue (91%), and anorexia (90%). The illness had a
      characteristic waxing and waning course, with 51 persons (89%) reporting
      recurring symptoms and 35 (61%) reporting illness lasting more than 3 weeks. By
      univariate analysis, infection was significantly associated (P<.05) with
      consumption of wine and a dessert containing raspberries, strawberries,
      blackberries, and blueberries. Only the dessert remained significant by
      stratified analysis with an adjusted relative risk of 2.1 (95% confidence
      interval, 1.4-3.2). CONCLUSIONS: Findings from this study support a point source
      outbreak of the newly identified pathogen C cayetanensis, with berries as the
      vehicle of transmission. It suggests that Cyclospora may cause severe diarrhea
      associated with profound anorexia and weight loss, and should be considered in
      the evaluation of prolonged gastrointestinal tract illness.

PMID- 9605785
TI  - The role of "colonization pressure" in the spread of vancomycin-resistant
      enterococci: an important infection control variable.
AB  - OBJECTIVE: The spread of nosocomial multiresistant microorganisms is affected by
      compliance with infection control measures and antibiotic use. We hypothesized
      that "colonization pressure" (ie, the proportion of other patients colonized)
      also is an important variable. We studied the effect of colonization pressure,
      compliance with infection control measures, antibiotic use, and other previously
      identified risk factors on acquisition of colonization with vancomycin-resistant
      enterococci (VRE). METHODS: Rectal colonization was studied daily for 19 weeks in
      181 consecutive patients who were admitted to a single medical intensive care
      unit. A statistical model was created using a Cox proportional hazards regression
      model including length of stay in the medical intensive care unit until
      acquisition of VRE, colonization pressure, personnel compliance with infection
      control measures (hand washing and glove use), APACHE (Acute Physiology and
      Chronic Health Evaluation) 11 scores, and the proportion of days that a patient
      received vancomycin or third-generation cephalosporins, sucralfate, and enteral
      feeding. RESULTS: With survival until colonization with VRE as the end point,
      colonization pressure was the most important variable affecting acquisition of
      VRE (hazard ratio [HR], 1.032; 95% confidence interval [C1], 1.012-1.052;
      P=.002). In addition, enteral feeding was associated with acquisition of VRE (HR,
      1.009; 95% CI, 1.000-1.017; P=.05), and there was a trend toward association of
      third-generation cephalosporin use with acquisition (HR, 1.007; 95% CI, 0.999
      1.015; P=.11). The effects of enteral feeding and third-generation cephalosporin
      use were more important when colonization pressure was less than 50%. Once
      colonization pressure was 50% or higher, these other variables hardly affected
      acquisition of VRE. CONCLUSIONS: Acquisition of VRE was affected by colonization
      pressure, the use of antibiotics, and the use of enteral feeding. However, once
      colonization pressure was high, it became the major variable affecting
      acquisition of VRE.

PMID- 9605786
TI  - Depressive symptoms and increased risk of stroke mortality over a 29-year period.
AB  - BACKGROUND: Several lines of evidence indicate that depression is importantly
      associated with cardiovascular disease end points. However, little is known about
      the role of depression in stroke mortality. METHODS: This study examined the
      association between depressive symptoms and stroke mortality in a prospective
      study of behavioral, social, and psychological factors related to health and
      mortality in a community sample of 6676 initially stroke-free adults (45.8% male;
      79.1% white; mean age at baseline, 43.4 years) from Alameda County, California.
      Depressive symptoms were assessed by the 18-item Human Population Laboratory
      Depression Scale. Cox proportional hazards regression models were used to
      evaluate the impact of depressive symptoms after controlling for age, sex, race,
      and other confounders. RESULTS: A total of 169 stroke deaths occurred during 29
      years of follow-up. Reporting 5 or more depressive symptoms at baseline was
      associated with increased risk of stroke mortality, after adjusting for age, sex,
      and race (hazard ratio, 1.66; 95% confidence interval, 1.16-2.39; P<.006). This
      association remained significant after additional adjustments for education,
      alcohol consumption, smoking, body mass index, hypertension, and diabetes (hazard
      ratio, 1.54; 95% confidence interval, 1.06-2.22; P<.02). Time-dependent covariate
      models, which allowed changes in reported depressive symptoms and risk factor
      levels during follow-up, revealed the same pattern of associations. CONCLUSIONS:
      This population-based study provides the strongest epidemiological evidence to
      date for a significant relationship between depressive symptoms and stroke
      mortality. These results contribute to the growing literature on the adverse
      health effects of depression.

PMID- 9605787
TI  - Effect of warfarin on activated partial thromboplastin time in patients receiving
      heparin.
AB  - BACKGROUND: The activated partial thromboplastin time (APTT) is used to adjust
      heparin sodium dosage. However, warfarin sodium is often administered
      concomitantly with heparin and may also affect the APTT and, therefore, heparin
      dose. We performed a prospective cohort study to quantify the effect of warfarin
      on the APTT in patients who are being treated with heparin. METHODS: Serial
      assays of APTT, international normalized ratio, heparin levels, and functional
      levels of prothrombin (factor II) and factors VII and X were performed in 24
      patients with acute venous thromboembolism who were treated with concomitant
      continuous intravenous heparin and warfarin. The effects of warfarin, as
      expressed by international normalized ratio and coagulation factor levels, on
      APTT were determined. RESULTS: Warfarin markedly affected APTT; for each increase
      of 1.0 in the international normalized ratio, the APTT increased 16 seconds (95%
      confidence interval, 10-22 seconds). The effects of warfarin and heparin on APTT
      were additive. Consequently, warfarin markedly altered the relationship between
      APTT and heparin levels; of the 29 blood samples with supratherapeutic APTT, 13
      had a therapeutic heparin level and 10 had a subtherapeutic heparin level.
      CONCLUSIONS: In patients receiving concomitant heparin and warfarin therapy, APTT
      reflects the combined effects of both drugs. Because of the marked effect of
      warfarin on the APTT, decreasing heparin dose in response to a high APTT
      frequently results in subtherapeutic heparin levels.

PMID- 9605788
TI  - Use of intensive care units for patients with low severity of illness.
AB  - OBJECTIVE: To determine variations among hospitals in use of intensive care units
      (ICUs) for patients with low severity of illness. DESIGN: Retrospective cohort
      study. SETTING: Twenty-eight hospitals with 44 ICUs in a large metropolitan
      region. PATIENTS: Consecutive eligible patients (N=104,487) admitted to medical,
      surgical, neurological, or mixed medical-surgical ICUs from March 1, 1991, to
      March 31, 1995. OUTCOME MEASURES: The predicted risk of in-hospital death for
      each patient was assessed using a validated method that is based on age, ICU
      admission source, diagnosis, severe comorbid conditions, and abnormalities in 17
      physiologic variables. Admissions were classified as low severity if the
      patient's predicted risk of death was less than 1%. In a subset of 12,929
      consecutive patients, use of 19 specific interventions typically delivered in
      ICUs was examined. RESULTS: Twenty thousand four hundred fifty-one admissions
      (19.6%) were categorized as low severity, including 23.6% of postoperative and
      16.9% of nonoperative admissions. Alcohol and other drug overdoses accounted for
      40.2% of nonoperative low-severity admissions; laminectomy and carotid
      endarterectomy accounted for 52.3% of postoperative low-severity admissions.
      Mortality among patients with low-severity illness was 0.3%, and only 28.6%
      received an ICU-specific intervention during the first ICU day. Although mean ICU
      length of stay was shorter (P<.001) in low-severity admissions (2.2 vs 4.7 days
      in nonoperative and 2.4 vs 4.2 days in postoperative admissions), low-severity
      admissions accounted for 11.1% of total ICU bed days. Rates of low-severity
      admissions varied (P<.001) across hospitals, ranging from 5% to 27% for
      nonoperative and 9% to 68% for postoperative admissions. CONCLUSIONS: A large
      proportion of patients admitted to the ICU have a low probability of death and do
      not receive ICU-specific interventions. Rates of low-severity admissions varied
      among hospitals. The development and implementation of protocols to target ICU
      care to patients most likely to benefit may decrease the number of low-severity
      ICU admissions and improve the cost-effectiveness of ICU care.

PMID- 9605789
TI  - Elevated serum digoxin level associated with coadministered fluoxetine.
AB  - After her daughter died, depression developed in a 93-year-old woman with
      congestive heart failure receiving digoxin therapy. After treatment with
      fluoxetine hydrochloride she became anorexic and her serum digoxin level
      increased. A possible interaction, which has not been reported in the literature,
      may have occurred between fluoxetine and digoxin.

PMID- 9605790
TI  - Do-not-resuscitate orders in critical care elderly: no age discrimination against
      elderly in a community hospital.

PMID- 9605791
TI  - Managed care bashing.

PMID- 9605792
TI  - Medical ethics in the treatment of Jehovah's Witnesses.

PMID- 9605793
TI  - Reversible hypothyroidism with corticotropin releasing hormone deficiency.

PMID- 9605794
TI  - The key to atherogenicity.

PMID- 9605795
TI  - A debt to African cities.

PMID- 9605796
TI  - Getting Hib vaccine to those who need it.

PMID- 9605797
TI  - Does neuroprotection improve stroke outcome?

PMID- 9605798
TI  - Public health and public choice: dammed off at China's Three Gorges?

PMID- 9605799
TI  - Tobacco tactics: not so passive about smoking after all.

PMID- 9605800
TI  - Cancer hopes and setbacks.

PMID- 9605801
TI  - Tamoxifen for early breast cancer: an overview of the randomised trials. Early
      Breast Cancer Trialists' Collaborative Group.
AB  - BACKGROUND: There have been many randomised trials of adjuvant tamoxifen among
      women with early breast cancer, and an updated overview of their results is
      presented. METHODS: In 1995, information was sought on each woman in any
      randomised trial that began before 1990 of adjuvant tamoxifen versus no tamoxifen
      before recurrence. Information was obtained and analysed centrally on each of
      37000 women in 55 such trials, comprising about 87% of the worldwide evidence.
      Compared with the previous such overview, this approximately doubles the amount
      of evidence from trials of about 5 years of tamoxifen and, taking all trials
      together, on events occurring more than 5 years after randomisation. FINDINGS:
      Nearly 8000 of the women had a low, or zero, level of the oestrogen-receptor
      protein (ER) measured in their primary tumour. Among them, the overall effects of
      tamoxifen appeared to be small, and subsequent analyses of recurrence and total
      mortality are restricted to the remaining women (18000 with ER-positive tumours,
      plus nearly 12000 more with untested tumours, of which an estimated 8000 would
      have been ER-positive). For trials of 1 year, 2 years, and about 5 years of
      adjuvant tamoxifen, the proportional recurrence reductions produced among these
      30000 women during about 10 years of follow-up were 21% (SD 3), 29% (SD 2), and
      47% (SD 3), respectively, with a highly significant trend towards greater effect
      with longer treatment (chi2(1)=52.0, 2p<0.00001). The corresponding proportional
      mortality reductions were 12% (SD 3), 17% (SD 3), and 26% (SD 4), respectively,
      and again the test for trend was significant (chi2(1) = 8.8, 2p=0.003). The
      absolute improvement in recurrence was greater during the first 5 years, whereas
      the improvement in survival grew steadily larger throughout the first 10 years.
      The proportional mortality reductions were similar for women with node-positive
      and node-negative disease, but the absolute mortality reductions were greater in
      node-positive women. In the trials of about 5 years of adjuvant tamoxifen the
      absolute improvements in 10-year survival were 10.9% (SD 2.5) for node-positive
      (61.4% vs 50.5% survival, 2p<0.00001) and 5.6% (SD 1.3) for node-negative (78.9%
      vs 73.3% survival, 2p<0.00001). These benefits appeared to be largely
      irrespective of age, menopausal status, daily tamoxifen dose (which was generally
      20 mg), and of whether chemotherapy had been given to both groups. In terms of
      other outcomes among all women studied (ie, including those with "ER-poor"
      tumours), the proportional reductions in contralateral breast cancer were 13% (SD
      13), 26% (SD 9), and 47% (SD 9) in the trials of 1, 2, or about 5 years of
      adjuvant tamoxifen. The incidence of endometrial cancer was approximately doubled
      in trials of 1 or 2 years of tamoxifen and approximately quadrupled in trials of
      5 years of tamoxifen (although the number of cases was small and these ratios
      were not significantly different from each other). The absolute decrease in
      contralateral breast cancer was about twice as large as the absolute increase in
      the incidence of endometrial cancer. Tamoxifen had no apparent effect on the
      incidence of colorectal cancer or, after exclusion of deaths from breast or
      endometrial cancer, on any of the other main categories of cause of death (total
      nearly 2000 such deaths; overall relative risk 0.99 [SD 0.05]). INTERPRETATION:
      For women with tumours that have been reliably shown to be ER-negative, adjuvant
      tamoxifen remains a matter for research. However, some years of adjuvant
      tamoxifen treatment substantially improves the 10-year survival of women with ER
      positive tumours and of women whose tumours are of unknown ER status, with the
      proportional reductions in breast cancer recurrence and in mortality appearing to
      be largely unaffected by other patient characteristics or treatments.

PMID- 9605802
TI  - Acute respiratory-tract infections and risk of first-time acute myocardial
      infarction.
AB  - BACKGROUND: There is growing interest in the role of infections in the aetiology
      of acute myocardial infarction (AMI). We undertook a large, population-based
      study to explore the association between risk of AMI and recent acute respiratory
      tract infection. METHODS: We used data from general practices in the UK (General
      Practice Research Database). Potential cases were people aged 75 years or
      younger, with no history of clinical risk factors, who had a first-time diagnosis
      of AMI between Jan 1, 1994, and Oct 31, 1996. Four controls were matched to each
      case on age, sex, and the practice attended. The date of the AMI in the case was
      defined as the index date. For both cases and controls the date of the last
      respiratory-tract infection before the index date was identified. We also did a
      case-crossover analysis of cases who had an acute respiratory-tract infection
      either before the index date or before an arbitrarily chosen date (1 year before
      AMI). FINDINGS: In the case-control analysis of 1922 cases and 7649 matched
      controls, significantly more cases than controls had an acute respiratory-tract
      infection in the 10 days before the index date (54 [2.8%] vs 72 [0.9%]). The odds
      ratios, adjusted for smoking and body-mass index, for first-time AMI in
      association with an acute respiratory-tract infection 1-5, 6-10, 11-15, or 16-30
      days before the index date (compared with participants who had no such infection
      during the preceding year) were 3.6 (95% CI 2.2-5.7), 2.3 (1.3-4.2), 1.8 (1.0
      3.3), and 1.0 (0.7-1.6); (test for trend p<0.01). The case-crossover analysis
      showed a relative risk of 2.7 (1.6-4.7) for AMI in relation to an acute
      respiratory-tract infection in the 10 days before the index date. INTERPRETATION:
      Our findings suggest that in people without a history of clinical risk factors
      for AMI, acute respiratory-tract infections are associated with an increased risk
      of AMI for a period of about 2 weeks. We cannot, however, completely exclude the
      possibility of misdiagnosis bias, if prodromal symptoms of AMI were mistaken for
      respiratory-tract infection.

PMID- 9605803
TI  - Economisation of vaccination against Haemophilus influenzae type b: a randomised
      trial of immunogenicity of fractional-dose and two-dose regimens.
AB  - BACKGROUND: The cost of Haemophilus influenzae type b (Hib) conjugate vaccines
      has limited their use in non-industrialised countries. To identify more
      economical vaccination schedules, we carried out a randomised trial of the
      immunogenicity of alternative regimens to the standard three-dose series.
      METHODS: 627 Chilean infants were randomly allocated to one of four regimens with
      either Hib polysaccharide-tetanus toxoid conjugate vaccine (PRP-T) or Hib
      oligosaccharide-diphtheria mutant toxoid conjugate vaccine (PRP-CRM197), for a
      total of eight groups. All infants receive diphtheria-tetanus-pertussis (DTP)
      vaccine at ages 2, 4, and 6 months. The regimens included three full doses, three
      fractional doses consisting of one half or one third of the full dose, and a
      regimen of two full doses (at age 4 and 6 months). The primary outcome was the
      proportion of infants with serum anti-polyribosylribitol phosphate (PRP, the type
      b capsular polysaccharide) concentrations of 0.15 microg/mL or more at age 8
      months. FINDINGS: 93% (95% CI 85-98) of infants vaccinated with three full doses
      of PRP-T or PRP-CRM197 (95% CI 84-98) achieved anti-PRP concentrations of 0.15
      microg/mL or more at age 8 months, compared with 91% (83-96) to 100% (95-100) of
      infants immunised with any fractional-dose regimen. Of the infants vaccinated
      with two doses of PRP-T or PRP-CRM197, 99% (93-100) and 87% (77-93) developed
      anti-PRP concentrations of 0.15 microg/mL or more, respectively. INTERPRETATION:
      91% (83-96) to 100% (95-100) of infants immunised with one-half or one-third of a
      full dose of Hib conjugate developed protective antibody concentrations. Carrier
      priming with DTP may make two-dose schedules an option in some places. These
      alternative regimens could bring the cost of Hib vaccines within reach of
      countries that currently cannot afford them.

PMID- 9605805
TI  - Restoration of voluntary emptying of the bladder by transplantation of innervated
      free skeletal muscle.
AB  - BACKGROUND: On the basis of studies with animals and experience with functioning
      muscle transfer in plastic surgery, we have developed a surgical technique to
      restore detrusor function for patients with bladder acontractility in whom there
      is no treatment alternative. METHODS: Three patients (aged 26 years, 28 years,
      and 68 years) with bladder acontractility as a result of spinal-cord injury (two
      patients) and chronic overdistension (one patient), who required catheterisation
      for bladder emptying for 5 years, 2 years, and 2 years, respectively, took part
      in our study. The patients were treated with microneurovascular free transfer of
      autologous latissimus dorsi muscle to the bladder to restore detrusor function.
      Follow-up included clinical and urodynamic evaluation, colour doppler sonography,
      intravenous urography, and flow-mode computerised tomography. FINDINGS: The three
      patients voluntarily emptied their bladders at 16 weeks, 16 weeks, and 30 weeks
      after surgery, respectively. There was no need for further catheterisation
      throughout the follow-up period. On urodynamic assessment at 12 months after the
      operation bladder capacity was found to be 600 mL, 600 mL, and 650 mL, residual
      urinary volume 0 mL, 50 mL, 90 mL, and maximum flow rate 26 mL/s, 25 mL/s, and 18
      mL/s, respectively. Activity at the transplanted latissimus dorsi was confirmed
      by ultrasonography and flow-mode computerised tomography. INTERPRETATION:
      Microneurovascular free transfer of latissimus dorsi muscle to functionally
      restore a deficient detrusor muscle has proved to be successful for the three
      patients in our study. This technique may also be an option to restore the
      function of other smooth-muscle organs.

PMID- 9605804
TI  - Randomised trial of effects of vitamin supplements on pregnancy outcomes and T
      cell counts in HIV-1-infected women in Tanzania.
AB  - BACKGROUND: In HIV-1-infected women, poor micronutrient status has been
      associated with faster progression of HIV-1 disease and adverse birth outcomes.
      We assessed the effects of vitamin A and multivitamins on birth outcomes in such
      women. METHODS: In Tanzania, 1075 HIV-1-infected pregnant women at between 12 and
      27 weeks' gestation received placebo (n=267), vitamin A (n=269), multivitamins
      excluding vitamin A (n=269), or multivitamins including vitamin A (n=270) in a
      randomised, double-blind, placebo-controlled trial with a 2x2 factorial design.
      We measured the effects of multivitamins and vitamin A on birth outcomes and
      counts of T lymphocyte subsets. We did analyses by intention to treat. RESULTS:
      30 fetal deaths occurred among women assigned multivitamins compared with 49
      among those not on multivitamins (relative risk 0.61 [95% CI 0.39-0.94] p=0.02).
      Multivitamin supplementation decreased the risk of low birthweight (<2500 g) by
      44% (0.56 [0.38-0.82] p=0.003), severe preterm birth (<34 weeks of gestation) by
      39% (0.61 [0.38-0.96] p=0.03), and small size for gestational age at birth by 43%
      (0.57 [0.39-0.82] p=0.002). Vitamin A supplementation had no significant effect
      on these variables. Multivitamins, but not vitamin A, resulted in a significant
      increase in CD4, CD8, and CD3 counts. INTERPRETATION: Multivitamin
      supplementation is a low-cost way of substantially decreasing adverse pregnancy
      outcomes and increasing T-cell counts in HIV-1-infected women. The clinical
      relevance of our findings for vertical transmission and clinical progression of
      HIV-1 disease is yet to be ascertained.

PMID- 9605806
TI  - A man with a Hippocratic syndrome?

PMID- 9605807
TI  - Hormone status of in-situ cancer in BRCA1 and BRCA2 mutation carriers.

PMID- 9605808
TI  - Variation in use of adjuvant tamoxifen.

PMID- 9605809
TI  - Detection of inhaled cat allergen.

PMID- 9605810
TI  - Raised serum IgE associated with reduced responsiveness to DPT vaccination during
      infancy.

PMID- 9605811
TI  - Prevalence of tuberous sclerosis estimated by capture-recapture analysis.

PMID- 9605812
TI  - Ca++ oscillation in endothelial cells and pre-eclampsia.

PMID- 9605813
TI  - Exhaled nitric oxide and pulmonary response to iloprost in systemic sclerosis
      with pulmonary hypertension.

PMID- 9605814
TI  - Cold hands, warm heart.

PMID- 9605815
TI  - WHO launches cautiously optimistic report on health.

PMID- 9605816
TI  - Photodynamic therapy begins to shine.

PMID- 9605817
TI  - Heat and dust in Sudan.

PMID- 9605819
TI  - Septic shock.

PMID- 9605820
TI  - Adjuvant cytotoxic chemotherapy for early breast cancer: doubts and decisions.

PMID- 9605821
TI  - Sodium intake and mortality.

PMID- 9605822
TI  - Sodium intake and mortality.

PMID- 9605823
TI  - Sodium intake and mortality.

PMID- 9605824
TI  - Impaired clearance of oxidised proteins in neurodegenerative diseases.

PMID- 9605825
TI  - Refutation of investigation commissioned by Karolinska Institute.

PMID- 9605826
TI  - Understanding premenstrual syndrome.

PMID- 9605827
TI  - Understanding premenstrual syndrome.

PMID- 9605828
TI  - High death rate from neoplasms in French diabetic and non-diabetic men.

PMID- 9605829
TI  - Cardiac troponins.

PMID- 9605830
TI  - Cardiac troponins.

PMID- 9605831
TI  - Transient cortical blindness after coronary angiography.

PMID- 9605832
TI  - Sex ratio of offspring of diabetics.

PMID- 9605833
TI  - Sex ratio of offspring of diabetics.

PMID- 9605834
TI  - Sex ratio of offspring of diabetics.

PMID- 9605835
TI  - Sex ratio of offspring of diabetics.

PMID- 9605836
TI  - Oral antifungal agents for onychomycosis.

PMID- 9605837
TI  - Diagnosing Lyme disease.

PMID- 9605838
TI  - Meta-analysis: is moving the goal post the answer?

PMID- 9605839
TI  - Ultra-rapid opiate detoxification under anaesthesia (UROD)

PMID- 9605840
TI  - Regional clearing for biomedical manuscripts.

PMID- 9605842
TI  - Multiple, polymorphic copies of SRY in both males and females of the vole
      Microtus cabrerae.
AB  - In mammals, sex determination is controlled by the Y-linked gene SRY. Although
      SRY is male-specific in most eutherian and marsupial species, with a single copy
      on the Y chromosome, several rodent species have multiple Y-linked copies of SRY,
      and two mole-vole species of the genus Ellobius determine sex without the Y
      chromosome or the SRY gene. We searched for homologs of SRY in three vole species
      of the genus Microtus and concluded that this gene is not male-specific in M.
      cabrerae, as it is present in multiple, polymorphic copies in both males and
      females. In contrast, SRY is male-specific in the related species M. agrestis and
      M. nivalis. Up to 15 different partial sequences of the SRY gene were found in M.
      cabrerae. Southern blots suggest that most of the extra copies of SRY are X
      linked. One of the copies observed only in males has a sequence identical to that
      of the SRY gene in M. agrestis and may represent a functional copy of the gene in
      this species. The rest are probably nonfunctional pseudogenes.

PMID- 9605843
TI  - Chromosomal mapping of the gene encoding serotonin N-acetyltransferase to rat
      chromosome 10q32.3 and mouse chromosome 11E2.
AB  - Pineal melatonin is produced during the night. Its nocturnal increase regulates
      circadian rhythms and the photoperiodic reproductive response. Serotonin is
      acetylated to N-acetylserotonin by serotonin N-acetyltransferase (SNAT) and then
      methylated to form melatonin by hydroxyindole-O-methyltransferase (HIOMT). The
      rhythmicity of melatonin synthesis is regulated by the rhythmic activity of SNAT.
      Most laboratory mice do not have melatonin because of a genetic defect in the
      activity of SNAT and/or HIOMT. In a previous study using a recombinant inbred
      strain, we have found that the locus controlling pineal SNAT activity (Nat4) is
      located on mouse Chromosome 11. Recently, SNAT has been cloned in the rat. In the
      present study, the gene encoding SNAT was localized, using a rat cDNA fragment,
      on rat and mouse chromosomes by direct R-banding fluorescence in situ
      hybridization (FISH). In addition, using molecular linkage analysis with
      interspecific backcross mice, a gene encoding SNAT was mapped on a mouse
      chromosome. The gene encoding SNAT was localized to rat chromosome 10q32.3 and
      mouse Chromosome 11E2 by FISH. The molecular linkage analysis demonstrated that
      the gene encoding SNAT maps 1.5 cM distal to D11Mit11. The data suggest that Nat4
      encodes SNAT. These chromosomal locations are in a region of conserved linkage
      homology between the two species.

PMID- 9605844
TI  - Genetic linkage mapping of 11 novel DNA markers and the ceruloplasmin (Cp) gene
      on rat chromosome 2.
AB  - We have mapped 11 novel, anonymous genetic markers to rat chromosome 2. The rat
      ceruloplasmin gene (Cp) had been previously mapped to chromosomes 2 and 7q11-
      >q13 by two different methods. To resolve the assignment and to localize the Cp
      gene on the rat genetic linkage map, we used linkage analysis to confirm that rat
      Cp lies on chromosome 2.

PMID- 9605845
TI  - Physical and linkage mapping of the bovine bone morphogenetic protein 1 on the
      evolutionary break region of BTA 8.
AB  - Bone morphogenetic protein 1 (BMP1) has been proposed as a regulatory molecule
      involved in the binding or activation of other BMP molecules. It has been
      described as being identical to the enzyme C-proteinase that processes
      procollagens to fibrillar collagens. A fragment containing an exon of the bovine
      BMP1 gene was amplified from an adapter-ligated genomic DNA library. The isolated
      bovine BMP1 fragment was assigned by fluorescence in situ hybridization (FISH) to
      bovine (BTA) chromosome 8q21, a region containing an evolutionary breakpoint
      between homology to human (HSA) chromosomes 8 and 9. The assignment to BTA 8 was
      confirmed by using a hybrid somatic cell panel. The 3' intron region of the
      amplified genomic BMP1 fragment showed a SSCP polymorphism, and linkage analysis
      in the International Bovine Reference Panel (IBRP) of families confirmed the
      boundary position of this gene. The BMP1 gene presents total linkage (theta =
      0.00, Z = 3.61) with the lipoprotein lipase gene on BTA 8 and HSA 8 and a larger
      recombination fraction (theta = 0.11, Z = 5.03) with the marker GGTB2 on BTA 8
      and HSA 9. Physical and genetic mapping of the bovine BMP1 gene contribute to
      narrow the boundary between the HSA 8 and HSA 9 homology segments on BTA 8 and to
      the comparative mapping between BTA 8, murine chromosome MMU 14, and HSA 8.

PMID- 9605846
TI  - Characteristics of two salmonid repetitive DNA families in rainbow trout,
      Oncorhynchus mykiss.
AB  - DNA sequence and genomic location of two repetitive DNA families in rainbow trout
      (Oncorhynchus mykiss) were investigated to develop molecular markers for
      chromosome identification. DNA fragments with sequences similar to the tandem and
      interspersed elements described in other salmonids were isolated. One clone
      showed differential hybridization to 12 pairs of chromosomes and should be a
      useful marker for physical mapping.

PMID- 9605847
TI  - Rapid isolation of genomic clones for individual members of human multigene
      families: identification and localisation of UBE2L4, a novel member of a
      ubiquitin conjugating enzyme dispersed gene family.
AB  - We describe a rapid, PCR-based, screening procedure for the isolation of human
      genomic clones in lambda bacteriophage, containing sequences coding for
      individual homologous members of a multigene family. The approach is based upon
      the identification, by dilution, of sub-pools of the genomic library that contain
      members of the gene family, prior to phage isolation. The presence of specific
      genes is established by PCR of aliquots of individually amplified library pools,
      using consensus primers and subsequent sequencing. We have used the approach to
      isolate a fourth member of the UBE2L gene family, UBE2L4, and located it on
      chromosome 19q13.1-->q13.2. This PCR-based approach to library screening has
      wider applicability in that it could be used to isolate alternate-spliced
      products from cDNA libraries.

PMID- 9605848
TI  - Assignment of the TCRA/TCRD locus to sheep chromosome bands 7q1.4-->q2.2 by
      fluorescence in situ hybridization.
AB  - Two genomic clones for the TCRA/TCRD locus have been isolated and characterized
      in sheep. The first clone corresponds to a new sheep Valpha element, the other to
      the entire Cdelta gene. Chromosomal mapping by fluorescence in situ hybridization
      (FISH) of Valpha and Cdelta clones localized the TCRA/TCRD locus on sheep
      chromosome region 7q14-->q22. This is the first physical assignment for genomic
      clones on sheep chromosome 7 by FISH. Moreover, the present data put the ovine
      7q14-->q22 and the human 14q11.2 regions in the same syntenic group.

PMID- 9605849
TI  - Assignment of the human kinectin gene (KTN1), encoding a kinesin-binding protein,
      to chromosome 14 band q22.1 by in situ hybridization.

PMID- 9605850
TI  - The two human organic cation transporter genes SLC22A1 and SLC22A2 are located on
      chromosome 6q26.
AB  - Polyspecific transporters for organic cations (OCT) belong to a new protein
      family which also include organic anion transporters. The first human
      transporters from this family (OCT1, OCT2) have been recently cloned. They
      translocate small cations like tetraethylammonium, choline and monoamine
      neurotransmitters and are involved in hepatic and renal cation excretion,
      respectively. We have localized the OCT1 and OCT2 genes (SLC22A1, SLC22A2) on
      chromosome 6q26.

PMID- 9605851
TI  - Assignment of STK6 to human chromosome 20q13.2-->q13.3 and a pseudogene STK6P to
      1q41-->q42.
AB  - Fluorescence in situ hybridization analysis of human STK6 encoding a mitotic
      centrosomal protein kinase, Aik, revealed two signals in chromosome bands 20q13.2
      ->q13.3 and 1q41-->q42. Somatic cell hybrid panel analyses showed the existence
      of an identical sequence to STK6 cDNA on chromosome 20, and a processed
      pseudogene on chromosome 1. These results suggest that STK6 is localized at 20q
      13.2-->q13.3 and a pseudogene STK6P at 1q41-->q42.

PMID- 9605852
TI  - A cytogenetically anchored genetic map of bovine chromosome 1 obtained by
      integrating flow-sorted chromosome-derived microsatellite markers into the
      international bovine map.
AB  - A genomic library was constructed from a peak of flow-sorted bovine chromosomes 1
      + X after PCR amplification. Forty-three bovine chromosome 1 microsatellites were
      isolated, genetically mapped and integrated in the international genetic map. In
      addition, BAC clones from a goat BAC library were identified for five markers
      (DVEPC119, INRA011, BM4307, KAP8 and MAF64). These goat BACs could be mapped by
      FISH onto bovine chromosome 1 to bands 1q44-->q45, 1q25, 1q21, 1q12 and 1q14-
      >q21, respectively. This map reduces the average interval between consecutive
      markers on the international bovine genetic map from 5.5 cM to 2.5 cM, and
      provides a good starting point for positional cloning projects in cattle, sheep
      or goats.

PMID- 9605853
TI  - Assignment of the STAT6 gene (STAT6) to human chromosome band 12q13 by in situ
      hybridization.

PMID- 9605854
TI  - Assignment of the Rab13 gene (RAB13) to human chromosome band 12q13 by in situ
      hybridization.

PMID- 9605855
TI  - Assignment of the DNA fragmentation factor gene (DFFA) to human chromosome bands
      1p36.3-->p36.2 by in situ hybridization.

PMID- 9605856
TI  - A novel allelic variant of the human serotonin transporter gene regulatory
      polymorphism.
AB  - Allelic variation of the human serotonin transporter gene (SLC6A4) has recently
      been shown to modulate anxiety-related traits. A tandemly repeated sequence in
      close proximity to the promoter was found to be represented by a long (L) and
      short (S) variant, differentially modulating gene expression in vitro.
      Specifically, allele S, generated by a deletion of 44 bp involving repeats VI to
      VIII, reduced transcriptional efficiency, gene expression, and 5
      hydroxytryptamine uptake and was associated with increased neuroticism scores. We
      have now identified a novel allelic variant of this promoter-linked polymorphism
      that is significantly larger than the L allele and which we have designated
      allele XL (for "extra large"). Sequence analysis revealed that XL arose through
      duplication of an internal segment composed of repeat elements VI to IX,
      comprising 85 bp in total, and, most notably, including the segments deleted in
      the S allele. Additional allelic variants larger than human allele L were
      observed predominantly in various nonhuman primates. Preliminary data indicated
      that these variable allelic extensions similarly originate from this specific
      repeat region. These allelic variants may serve as a valuable model system to
      further elucidate the relationship between repeat structure, regulatory
      properties, and behavioral correlates. Finally, allelic variants were found to
      vary significantly among different human populations, with allele XL being
      uniquely present in individuals of African origin, allele L most frequent in
      Africans and Caucasians of Western European descent, and allele S most abundant
      in East Asians.

PMID- 9605857
TI  - Fluorescence in situ hybridization mapping of the alpha and beta subunits (HADHA
      and HADHB) of human mitochondrial fatty acid beta-oxidation multienzyme complex
      to 2p23 and their evolution.
AB  - Mitochondrial fatty acid beta-oxidation multienzyme complex/trifunctional protein
      has an alpha4beta4 structure and catalyzes the second through fourth reactions of
      the fatty acid beta-oxidation cycle. The alpha and beta subunits (HADHA and
      HADHB) are members of the enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase and
      3-ketoacyl-CoA thiolase families, respectively. We analyzed the localization of
      each of these two genes (HADHA and HADHB) by in situ hybridization and found that
      both can be assigned to human chromosome band 2p23. Since the distance between
      the two loci is quite short, the two genes seem to exist side by side, as do the
      two (A and B subunit) genes of the bacterial fatty acid beta-oxidation
      multienzyme complex. This is an important and interesting finding in that two
      entirely different genes, encoding two independent proteins forming a multienzyme
      complex, are adjacent on chromosome band 2p23.

PMID- 9605858
TI  - Synteny mapping of four genes from the short arm of human chromosome 19 to bovine
      chromosome 7.
AB  - Four genes on the short arm of human chromosome 19 (HSA 19p) were assigned to
      bovine chromosome 7 (BTA 7) using a bovine x rodent somatic hybrid cell panel.
      These four genes were cartilage oligomeric matrix protein (COMP), lymphoblastic
      leukemia derived sequence 1 (LYL1), lysosomal alpha-mannosidase (MANB), and RAS
      oncogene family member RAB3A. Bovine sequence tagged sites were developed for the
      four genes and used for screening a bovine x rodent somatic cell panel. All four
      genes were mapped to bovine synteny group U22 (BTA 7) with a correlation
      coefficient of 0.901-1.000. This study confirms that the centromeric region of
      BTA 7 is conserved with HSA 19p.

PMID- 9605859
TI  - Assignment of the ARHA and GPX1 genes to human chromosome bands 3p21.3 by in situ
      hybridization and with somatic cell hybrids.

PMID- 9605860
TI  - Assignment of pancreatic zymogen granule membrane protein GP2 (GP2) to human
      chromosome band 9q21.11 to q21.2 by in situ hybridization.

PMID- 9605861
TI  - Assignment of a UDP-glucose:ceramide glucosyltransferase gene (UGCG) to human
      chromosome band 9q31 by in situ hybridization.

PMID- 9605862
TI  - Assignment of the evolutionarily conserved CD1D class gene (Cd1d) to rat
      chromosome 7q32.

PMID- 9605864
TI  - Assignment of the Tamm-Horsfall protein/uromodulin gene (Umod) to mouse
      chromosome bands 7F1-F2 and rat chromosome bands 1q36-->q37 by in situ
      hybridization.

PMID- 9605863
TI  - Genomic cloning and localization of CTAG, a gene encoding an autoimmunogenic
      cancer-testis antigen NY-ESO-1, to human chromosome Xq28.
AB  - CTAG was initially cloned from an esophageal squamous cell carcinoma cDNA
      expression library by immunoscreening with autologous patient's serum. CTAG mRNA
      is expressed in a proportion of human cancers in a lineage-nonspecific fashion,
      whereas its expression in normal tissues is restricted to testis and ovary only.
      This expression pattern suggests that the CTAG product (NY-ESO-1) is an
      aberrantly activated tumor antigen and can potentially be an antigenic target for
      tumor vaccination. In the present study, we isolated human genomic clones of CTAG
      and established its genomic organization. By somatic cell hybrid studies and
      fluorescence in-situ hybridization, we localized this gene to chromosome Xq28, a
      region that also contains members of MAGE, a gene family that encodes several
      immunogenic tumor antigens with the characteristic cancer/testis expression
      pattern.

PMID- 9605865
TI  - A mouse gene (Dgcr6) related to the Drosophila gonadal gene is expressed in early
      embryogenesis and is the homolog of a human gene deleted in DiGeorge syndrome.
AB  - We report the identification of a mouse gene, Dgcr6, which shows high sequence
      similarity to gonadal (gdl), a Drosophila gene of unknown function. Dgcr6 is the
      mouse homolog of human DGCR6, previously shown to be deleted in DiGeorge
      syndrome, a developmental field defect affecting the derivatives of the
      pharyngeal arches which is associated with 22q11.2 deletions. The Dgcr6
      transcript has a 594 nucleotide open reading frame (ORF) encoding 198 amino
      acids. We previously mapped Dgcr6 to mouse chromosome 16B1-B3, a region known to
      contain other mouse homologs of genes deleted in DiGeorge syndrome. Expression
      studies were performed by Northern blotting analysis on mouse embryo and adult
      tissues and by RNA in situ hybridization on mouse embryo sections. Results show
      that Dgcr6 transcripts are abundant during mouse embryogenesis, from at least 7
      days post coitum. In particular, high expression was detected in the brain,
      spinal cord and pharyngeal arches. On adult tissues high expression was detected
      in testis. The function of Dgcr6 is to be determined, but its developmental
      expression suggests that this gene may play a role in the developmental defects
      associated with 22q11.2 deletions.

PMID- 9605866
TI  - Mapping of 34 minisatellite loci resolved by two-dimensional DNA typing.
AB  - Two-dimensional (2-D) DNA typing is based on electrophoretic separation of
      genomic DNA fragments in two dimensions according to independent criteria (size
      and base-pair sequence), followed by hybridization analysis using multilocus
      probes. The technique allows simultaneous visualization of several hundred loci
      as spots in a 2-D pattern. The majority of the loci resolved are polymorphic.
      Using linkage analysis in a large CEPH family, this study reports the mapping of
      34 loci detected by the minisatellite core probe 33.6. By multipoint linkage
      analysis, regional chromosome positions of the 33.6 loci could be deduced,
      showing no evidence of clustering. In the analysis of spot patterns, use was made
      of a computerized image analysis system specifically designed for 2-D DNA typing.
      Since experimental variations between different separation patterns were
      automatically corrected for with this program, rapid and reliable scorings could
      be obtained. The results presented demonstrate the availability of reliable
      genetic information throughout the 2-D separation pattern. Adding the use of
      semiautomated computerized pattern analysis, this study further substantiates the
      applicability of 2-D DNA typing in genome scanning, not only in theoretical but
      also in practical terms. Moreover, it can be anticipated that this method will
      have a specific advantage in studies that scan for trinucleotide repeat
      expansions and somatic instability, where the repeat sequences detected by
      appropriate core probes are of particular interest.

PMID- 9605867
TI  - Map integration at human chromosome 10: molecular and cytogenetic analysis of a
      chromosome-specific somatic cell hybrid panel and genomic clones, based on a well
      supported genetic map.
AB  - Well-characterized, chromosome-specific somatic cell hybrid panels are powerful
      tools for the analysis of the human genome. We have characterized a panel of
      human x hamster somatic cell hybrids retaining fragments of human chromosome 10
      by fluorescence in situ hybridization and associated them to genetic markers.
      Most of the hybrids were generated by the radiation-reduction method, starting
      from a chromosome 10-specific monochromosomal hybrid, whereas some were collected
      from hybrids retaining chromosome 10-specific fragments as a result of
      spontaneous in vitro rearrangements. PCR was used to score the retention of 57
      microsatellite markers evenly distributed along a well-supported framework
      genetic map containing 149 loci uniquely placed at 69 anchor points (odds
      exceeding 1,000:1), with an average spacing of 2.8 cM. As an additional resource
      for genomic studies involving human chromosome 10, we report the cytogenetic
      localization of a series of YAC and PAC clones recognized by at least one genetic
      marker. Somatic cell hybrids provide a powerful source of partial chromosome
      paints useful for detailed clinical cytogenetic and primate chromosome evolution
      investigations. Furthermore, correlation of the above physical, genetic, and
      cytogenetic data contribute to an emerging consensus map of human chromosome 10.

PMID- 9605868
TI  - Heterochromatin heterogeneity and chromosome variability in four species of
      gobiid fishes (Perciformes:Gobiidae).
AB  - A karyological study of four species of gobiid fishes, Gobius niger, G.
      paganellus, G. cobitis, and Zosterisessor ophiocephalus (Perciformes, Gobiidae),
      was conducted by standard, fluorochrome staining (using chromomycin A3,
      mithramycin, and DAPI), Alu-I digestion, and CBG- and RBG-banding methods. Our
      cytogenetic data indicate that heterochromatin in these taxa is highly
      differentiated, exhibiting heterogeneity in staining characteristics, and
      presumably in underlying DNA sequences, and a different capability for promoting
      Robertsonian fusions.

PMID- 9605869
TI  - Assignment of the human cardiac troponin I gene (TNNI3) to chromosome 19q13.4 by
      radiation hybrid mapping.

PMID- 9605870
TI  - Assignment of the gene for a developmentally regulated GTP-binding protein (DRG2)
      to human chromosome bands 17p13-->p12 by in situ hybridization.

PMID- 9605871
TI  - Definition of the critical interval for Smith-Magenis syndrome.
AB  - Smith-Magenis syndrome (SMS) comprises a complex physical and behavioral
      phenotype that is associated with an interstitial deletion of chromosome 17p11.2.
      The deletions observed in patients can range from <2 to >9 megabases of DNA and
      may include more than 100 genes. In order to determine the critical deletion
      interval responsible for the syndrome phenotype, we have examined several
      patients with varying deletions involving 17p11.2 by somatic cell hybrid
      analyses. We have binned 112 markers along 17p11.2, including 27 markers within
      the critical interval for SMS, which is bound proximally by D17S29 and distally
      by cCI17-638. In addition, we present two patients who carry deletions involving
      17p11.2 but do not exhibit the typical features of SMS. Patients such as these
      will allow genotype:phenotype correlations to be made and the gene(s) responsible
      for the SMS phenotype to be determined.

PMID- 9605872
TI  - Assignment of IL12RB2 to human chromosome 1p31.3-->p31.2 between D1S230 and
      D1S198.

PMID- 9605873
TI  - Assignment of SAFB encoding Hsp27 ERE-TATA binding protein (HET)/scaffold
      attachment factor B (SAF-B) to human chromosome 19 band p13.

PMID- 9605874
TI  - Assignment of ISG20 encoding a new interferon-induced PML nuclear body-associated
      protein, to chromosome 15q26 by in situ hybridization.

PMID- 9605875
TI  - Cytogenetics of collared lemmings (Dicrostonyx groenlandicus). I. Meiotic
      behavior and evolution of the neo-XY sex-chromosome system.
AB  - Electron-microscopic analysis of surface-spread synaptonemal complexes at
      pachynema and light-microscopic analysis of chromosomal configurations at
      diakinesis/metaphase I corroborate the hypothesized neo-XY derivation of the sex
      chromosomes of Dicrostonyx groenlandicus. Although an intact neo-XY pairing
      configuration was observed in a relatively small percentage of the pachytene
      cells in each individual, the high incidence of neo-XY bivalents at
      diakinesis/metaphase I suggests that the other observed pachytene configurations
      were artifacts of the physical stresses of the surface-spreading procedure. The
      very low frequency (0.6%) of univalent neo-X and neo-Y chromosomes at diakinesis
      and metaphase I is attributable to consistent synapsis and recombination between
      their homologous autosomally derived segments. The resultant stability of the sex
      bivalent through metaphase I may have increased the efficacy of sex-chromosome
      segregation, and thereby played a mechanistic role in the evolutionary
      incorporation of the neo-XY sex-chromosome constitution in D. groenlandicus.

PMID- 9605876
TI  - Identification of positional candidates for neurological disorders on chromsome
      13q14-->q22.
AB  - In the course of a research project aimed at the molecular characterization of
      balanced chromosome rearrangements associated with mental retardation (MR),
      several YACs spanning MR-associated chromosomal rearrangements in the 13q14-->q22
      region were identified. To facilitate the search for relevant candidate genes, we
      have analyzed a total of 102 EST clones from this region. Sequence comparisons
      revealed that these 102 clones represent up to 72 distinct transcripts. When no
      physical mapping data were available, a minimal YAC contig was screened for each
      unique transcript by the polymerase chain reaction (PCR) or hybridization. Fifty
      eight independent ESTs could be localized to YAC clones between the markers
      D13S1248 and D13S1201. Several ESTs are located on YAC clones detecting
      chromosomal rearrangements in MR patients. One EST was mapped within the critical
      region for Rieger syndrome type 2, and three transcripts were identified in the
      region for the nocturnal enuresis type 1. Some ESTs showed homologies to known
      genes, including the cadherin-related tumor suppressor gene from Drosophila, the
      yeast mitotic control protein DIS3, and the human alpha-2-macroglobulin receptor
      associated protein.

PMID- 9605877
TI  - Chromosomal localization of mouse Cenpa gene.
AB  - Using a previously isolated mouse centromere protein A (Cenpa) probe, we have
      localized the gene to the proximal region of mouse Chromosome 5, between the
      known Il6 and Yes1 loci near [Adra2C-D5H4S43-Hdh]. Comparison of this
      localization with that of human CENPA, which maps to chromosome 2, is consistent
      with the presence of a new region of conserved synteny between the two species.

PMID- 9605878
TI  - Using ventricular assist devices as long-term therapy for heart failure.

PMID- 9605879
TI  - Domestic violence recognized as world problem.

PMID- 9605880
TI  - MediCaring Project to demonstrate, evaluate innovative end-of-life program for
      chronically ill.

PMID- 9605881
TI  - From the AMA Council on Scientific Affairs. Heat-related illness during extreme
      weather emergencies.

PMID- 9605882
TI  - From the Centers for Disease Control and Prevention. Tuberculosis morbidity-
      United States, 1997.

PMID- 9605883
TI  - From the Centers for Disease Control and Prevention. Update: influenza activity-
      United States and worldwide, 1997-98 season, and composition of the 1998-99
      influenza vaccine.

PMID- 9605884
TI  - A piece of my mind. Holding the heart.

PMID- 9605885
TI  - Emerging ethical issues in palliative care.

PMID- 9605886
TI  - Insulin treatment for type 2 diabetes.

PMID- 9605887
TI  - Insulin treatment for type 2 diabetes.

PMID- 9605888
TI  - Insulin treatment for type 2 diabetes.

PMID- 9605889
TI  - Insulin treatment for type 2 diabetes.

PMID- 9605890
TI  - Insulin treatment for type 2 diabetes.

PMID- 9605891
TI  - Insulin treatment for type 2 diabetes.

PMID- 9605892
TI  - Concerns about run-in periods in randomized trials.

PMID- 9605893
TI  - Concerns about run-in periods in randomized trials.

PMID- 9605894
TI  - Concerns about run-in periods in randomized trials.

PMID- 9605895
TI  - SV40-contaminated poliovirus vaccine and childhood cancer risk.

PMID- 9605896
TI  - Abstinence and safer sex HIV risk-reduction interventions for African American
      adolescents: a randomized controlled trial.
AB  - CONTEXT: African American adolescents are at high risk of contracting sexually
      transmitted infection with human immunodeficiency virus (HIV), but which
      behavioral interventions to reduce risk are most effective and who should conduct
      them is not known. OBJECTIVE: To evaluate the effects of abstinence and safer-sex
      HIV risk-reduction interventions on young inner-city African American
      adolescents' HIV sexual risk behaviors when implemented by adult facilitators as
      compared with peer cofacilitators. DESIGN: Randomized controlled trial with 3-, 6
      , and 12-month follow-up. SETTING: Three middle schools serving low-income
      African American communities in Philadelphia, Pa. PARTICIPANTS: A total of 659
      African American adolescents recruited for a Saturday program. INTERVENTIONS:
      Based on cognitive-behavioral theories and elicitation research, interventions
      involved 8 1-hour modules implemented by adult facilitators or peer
      cofacilitators. Abstinence intervention stressed delaying sexual intercourse or
      reducing its frequency; safer-sex intervention stressed condom use; control
      intervention concerned health issues unrelated to sexual behavior. MAIN OUTCOME
      MEASURES: Self-reported sexual intercourse, condom use, and unprotected sexual
      intercourse. RESULTS: Mean age of the enrollees was 11.8 years; 53% were female
      and 92.6% were still enrolled at 12 months. Abstinence intervention participants
      were less likely to report having sexual intercourse in the 3 months after
      intervention than were control group participants (12.5% vs 21.5%, P=.02), but
      not at 6- or 12-month follow-up (17.2% vs 22.7%, P=.14; 20.0% vs 23.1%, P=.42,
      respectively). Safer-sex intervention participants reported significantly more
      consistent condom use than did control group participants at 3 months (odds ratio
      [OR]=3.38; 95% confidence interval [CI], 1.25-9.16) and higher frequency of
      condom use at all follow-ups. Among adolescents who reported sexual experience at
      baseline, the safer-sex intervention group reported less sexual intercourse in
      the previous 3 months at 6- and 12-month follow-up than did control and
      abstinence intervention (adjusted mean days over prior 3 months, 1.34 vs 3.77 and
      3.03, respectively; P< or =.01 at 12- month follow-up) and less unprotected
      intercourse at all follow-ups than did control group (adjusted mean days, 0.04 vs
      1.85, respectively, P<.001, at 12-month follow-up). There were no differences in
      intervention effects with adult facilitators as compared with peer
      cofacilitators. CONCLUSION: Both abstinence and safer-sex interventions can
      reduce HIV sexual risk behaviors, but safer-sex interventions may be especially
      effective with sexually experienced adolescents and may have longer-lasting
      effects.

PMID- 9605897
TI  - Role of rifampin for treatment of orthopedic implant-related staphylococcal
      infections: a randomized controlled trial. Foreign-Body Infection (FBI) Study
      Group.
AB  - CONTEXT: Rifampin-containing regimens are able to cure staphylococcal implant
      related infections based on in vitro and in vivo observations. However, this
      evidence has not been proven by a controlled clinical trial. OBJECTIVE: To
      evaluate the clinical efficacy of a rifampin combination in staphylococcal
      infections associated with stable orthopedic devices. DESIGN: A randomized,
      placebo-controlled, double-blind trial conducted from 1992 through 1997. SETTING:
      Two infectious disease services in tertiary care centers in collaboration with 5
      orthopedic surgeons in Switzerland. PATIENTS: A total of 33 patients with culture
      proven staphylococcal infection associated with stable orthopedic implants and
      with a short duration of symptoms of infection (exclusion limit <1 year; actual
      experience 0-21 days). INTERVENTION: Initial debridement and 2-week intravenous
      course of flucloxacillin or vancomycin with rifampin or placebo, followed by
      either ciprofloxacin-rifampin or ciprofloxacin-placebo long-term therapy. MAIN
      OUTCOME MEASURES: Cure was defined as (1) lack of clinical signs and symptoms of
      infection, (2) C-reactive protein level less than 5 mg/L, and (3) absence of
      radiological signs of loosening or infection at the final follow-up visit at 24
      months. Failure was defined as (1) persisting clinical and/or laboratory signs of
      infection or (2) persisting or new isolation of the initial microorganism.
      RESULTS: A total of 18 patients were allocated to ciprofloxacin-rifampin and 15
      patients to the ciprofloxacin-placebo combination. Twenty-four patients fully
      completed the trial with a follow-up of 35 and 33 months. The cure rate was 12
      (100%) of 12 in the ciprofloxacin-rifampin group compared with 7 (58%) of 12 in
      the ciprofloxacin-placebo group (P=.02). Nine of 33 patients dropped out due to
      adverse events (n=6), noncompliance (n=1), or protocol violation (n=2). Seven of
      the 9 patients who dropped out were subsequently treated with rifampin
      combinations, and 5 of them were cured without removal of the device. CONCLUSION:
      Among patients with stable implants, short duration of infection, and initial
      debridement, patients able to tolerate long-term (3-6 months) therapy with
      rifampin-ciprofloxacin experienced cure of the infection without removal of the
      implant.

PMID- 9605899
TI  - Why patients use alternative medicine: results of a national study.
AB  - CONTEXT: Research both in the United States and abroad suggests that significant
      numbers of people are involved with various forms of alternative medicine.
      However, the reasons for such use are, at present, poorly understood. OBJECTIVE:
      To investigate possible predictors of alternative health care use. METHODS: Three
      primary hypotheses were tested. People seek out these alternatives because (1)
      they are dissatisfied in some way with conventional treatment; (2) they see
      alternative treatments as offering more personal autonomy and control over health
      care decisions; and (3) the alternatives are seen as more compatible with the
      patients' values, worldview, or beliefs regarding the nature and meaning of
      health and illness. Additional predictor variables explored included demographics
      and health status. DESIGN: A written survey examining use of alternative health
      care, health status, values, and attitudes toward conventional medicine. Multiple
      logistic regression analyses were used in an effort to identify predictors of
      alternative health care use. SETTING AND PARTICIPANTS: A total of 1035
      individuals randomly selected from a panel who had agreed to participate in mail
      surveys and who live throughout the United States. MAIN OUTCOME MEASURE: Use of
      alternative medicine within the previous year. RESULTS: The response rate was
      69%. The following variables emerged as predictors of alternative health care
      use: more education (odds ratio [OR], 1.2; 95% confidence interval [CI], 1.1
      1.3); poorer health status (OR, 1.3; 95% CI, 1.1-1.5); a holistic orientation to
      health (OR, 1.4; 95% CI, 1.1-1.9); having had a transformational experience that
      changed the person's worldview (OR, 1 .8; 95% CI, 1 .3-2.5); any of the following
      health problems: anxiety (OR, 3.1; 95% CI, 1.6-6.0); back problems (OR, 2.3; 95%
      CI, 1 .7-3.2); chronic pain (OR, 2.0; 95% CI, 1.1 -3.5); urinarytract problems
      (OR, 2.2; 95% CI, 1.3-3.5); and classification in a cultural group identifiable
      by their commitment to environmentalism, commitment to feminism, and interest in
      spirituality and personal growth psychology (OR, 2.0; 95% CI, 1.4-2.7).
      Dissatisfaction with conventional medicine did not predict use of alternative
      medicine. Only 4.4% of those surveyed reported relying primarily on alternative
      therapies. CONCLUSION: Along with being more educated and reporting poorer health
      status, the majority of alternative medicine users appear to be doing so not so
      much as a result of being dissatisfied with conventional medicine but largely
      because they find these health care alternatives to be more congruent with their
      own values, beliefs, and philosophical orientations toward health and life.

PMID- 9605898
TI  - Use of the percentage of free prostate-specific antigen to enhance
      differentiation of prostate cancer from benign prostatic disease: a prospective
      multicenter clinical trial.
AB  - CONTEXT: The percentage of free prostate-specific antigen (PSA) in serum has been
      shown to enhance the specificity of PSA testing for prostate cancer detection,
      but earlier studies provided only preliminary cutoffs for clinical use.
      OBJECTIVE: To develop risk assessment guidelines and a cutoff value for defining
      abnormal percentage of free PSA in a population of men to whom the test would be
      applied. DESIGN: Prospective blinded study using the Tandem PSA and free PSA
      assays (Hybritech Inc, San Diego, Calif). SETTING: Seven nationwide university
      medical centers. PARTICIPANTS: A total of 773 men (379 with prostate cancer, 394
      with benign prostatic disease) 50 to 75 years of age with a palpably benign
      prostate gland, PSA level of 4.0 to 10.0 ng/mL, and histologically confirmed
      diagnosis. MAIN OUTCOME MEASURES: A percentage of free PSA cutoff that maintained
      95% sensitivity for prostate cancer detection, and probability of cancer for
      individual patients. RESULTS: The percentage of free PSA may be used in 2 ways:
      as a single cut-off (ie, perform a biopsy for all patients at or below a cutoff
      of 25% free PSA) or as an individual patient risk assessment (ie, base biopsy
      decisions on each patient's risk of cancer). The 25% free PSA cutoff detected 95%
      of cancers while avoiding 20% of unnecessary biopsies. The cancers associated
      with greater than 25% free PSA were more prevalent in older patients, and
      generally were less threatening in terms of tumor grade and volume. For
      individual patients, a lower percentage of free PSA was associated with a higher
      risk of cancer (range, 8%-56%). In the multivariate model used, the percentage of
      free PSA was an independent predictor of prostate cancer (odds ratio [OR], 3.2;
      95% confidence interval [CI], 2.5-4.1; P < .001) and contributed significantly
      more than age (OR, 1.2; 95% CI, 0.92-1.55) or total PSA level (OR, 1.0; 95% CI,
      0.92-1.11) in this cohort of subjects with total PSA values between 4.0 and 10.0
      ng/mL. CONCLUSIONS: Use of the percentage of free PSA can reduce unnecessary
      biopsies in patients undergoing evaluation for prostate cancer, with a minimal
      loss in sensitivity in detecting cancer. A cutoff of 25% or less free PSA is
      recommended for patients with PSA values between 4.0 and 10.0 ng/mL and a
      palpably benign gland, regardless of patient age or prostate size. To our
      knowledge, this study is the largest series to date evaluating the percentage of
      free PSA in a population representative of patients in whom the test would be
      used in clinical practice.

PMID- 9605900
TI  - Comparison of molecular changes in lung cancers in HIV-positive and HIV
      indeterminate subjects.
AB  - CONTEXT: Human immunodeficiency virus (HIV) infection has been associated with an
      increasing incidence of malignancy, and HIV-infected persons have an increased
      incidence of primary lung carcinoma compared with the general population.
      OBJECTIVE: To investigate the molecular changes present in HIV-associated lung
      tumors and compare them with those present in lung carcinomas arising in HIV
      indeterminate subjects ("sporadic tumors"). DESIGN: Convenience sample. SUBJECTS:
      Archival tissues from 11 HIV-positive persons and from 35 persons of
      indeterminate HIV status. SETTING: University-based medical centers and
      affiliated hospitals. MAIN OUTCOME MEASURES: Analysis of frequency of loss of
      heterozygosity (LOH) and microsatellite alteration (MA) using polymerase chain
      reaction and 16 polymorphic microsatellite markers at 8 chromosomal regions
      frequently deleted in lung cancer. Presence of HIV and human papillomavirus (HPV)
      sequences. RESULTS: The overall frequency of LOH at all chromosomal regions
      tested and the frequencies at most of the individual regions were similar in the
      2 groups. Frequency of MA present in the HIV-associated tumors (0.18) was 6-fold
      higher than in sporadic tumors (0.03) (P<.001). At least 1 MA was present in 10
      (91%) of 11 HIV-associated tumors vs 17 (48%) of 35 sporadic tumors (P=.02).
      Molecular changes were independent of tumor stage and gender. HIV and HPV
      sequences were not detected in the HIV-associated lung carcinomas. CONCLUSIONS:
      Microsatellite alterations, which reflect widespread genomic instability, occur
      at greatly increased frequency in HIV-associated lung carcinomas. Although the
      mechanism underlying the development of increased MAs is unknown, it may play a
      crucial role in the development of many HIV-associated tumors.

PMID- 9605901
TI  - Reorganizing an academic medical service: impact on cost, quality, patient
      satisfaction, and education.
AB  - CONTEXT: Academic medical centers are under enormous pressure to improve quality
      and cut costs while preserving education. OBJECTIVE: To determine whether a
      reorganized academic medical service, led by faculty members who attended more
      often and became involved earlier and more intensively in care, would lower costs
      without compromising quality and education. DESIGN: Alternate-day controlled
      trial. SETTING: Inpatient academic general medical service. PATIENTS: The 1623
      patients discharged from the Moffitt-Long medical service between July 1, 1995,
      and June 30, 1996. INTERVENTIONS: We divided our 4-team inpatient general medical
      service into 2 managed care service (MCS) teams and 2 traditional service (TS)
      teams. The MCS faculty served as attending physicians more often and were
      required to provide early input into clinical decisions. Patients were assigned
      to teams based on alternate days of admission. MAIN OUTCOME MEASURES: Outcome
      measures included resource use and outcomes for MCS vs TS patients, and for MCS
      patients vs patients seen the previous year, adjusted for demographic
      characteristics and case mix. Satisfaction of patients, house staff, and faculty
      was also assessed, as was educational emphasis. RESULTS: A total of 806 patients
      were admitted to the MCS and 817 to the TS. Demographic characteristics and case
      mix were similar. Clinical outcomes, including mortality and readmission rates,
      were also similar, as was patient satisfaction. Resident and faculty satisfaction
      were high on both services. The average adjusted length of stay of patients on
      the MCS was 4.3 days vs 4.9 days on the TS and 5 days in 1994-1995 (adjusted
      P=.01 for MCS vs TS; MCS vs 1994-1995, P<.001). Average adjusted hospital costs
      were $7007 on the MCS vs $7777 on the TS and $8078 in 1994-1995 (adjusted P=.05
      for MCS vs TS; MCS vs 1994-1995, P=.002). CONCLUSIONS: A reorganized academic
      medical service, led by faculty members who attended more often and became
      involved earlier and more intensively, resulted in significant resource savings
      with no changes in clinical outcomes or patient, faculty, and house staff
      satisfaction.

PMID- 9605902
TI  - Why review articles on the health effects of passive smoking reach different
      conclusions.
AB  - OBJECTIVE: To determine whether the conclusions of review articles on the health
      effects of passive smoking are associated with article quality, the affiliations
      of their authors, or other article characteristics. DATA SOURCES: Review articles
      published from 1980 to 1995 were identified through electronic searches of
      MEDLINE and EMBASE and from a database of symposium proceedings on passive
      smoking. ARTICLE SELECTION: An article was included if its stated or implied
      purpose was to review the scientific evidence that passive smoking is associated
      with 1 or more health outcomes. Articles were excluded if they did not focus
      specifically on the health effects of passive smoking or if they were not written
      in English. DATA EXTRACTION: Review article quality was evaluated by 2
      independent assessors who were trained, followed a written protocol, had no
      disclosed conflicts of interest, and were blinded to all study hypotheses and
      identifying characteristics of articles. Article conclusions were categorized by
      the 2 assessors and by one of the authors. Author affiliation was classified as
      either tobacco industry affiliated or not, based on whether the authors were
      known to have received funding from or participated in activities sponsored by
      the tobacco industry. Other article characteristics were classified by one of the
      authors using predefined criteria. DATA SYNTHESIS: A total of 106 reviews were
      identified. Overall, 37% (39/106) of reviews concluded that passive smoking is
      not harmful to health; 74% (29/39) of these were written by authors with tobacco
      industry affiliations. In multiple logistic regression analyses controlling for
      article quality, peer review status, article topic, and year of publication, the
      only factor associated with concluding that passive smoking is not harmful was
      whether an author was affiliated with the tobacco industry (odds ratio, 88.4; 95%
      confidence interval, 16.4-476.5; P<.001). CONCLUSIONS: The conclusions of review
      articles are strongly associated with the affiliations of their authors. Authors
      of review articles should disclose potential financial conflicts of interest, and
      readers of review articles should consider authors' affiliations when deciding
      how to judge an article's conclusions.

PMID- 9605903
TI  - Time to act on drug safety.

PMID- 9605904
TI  - Preventing sexually transmitted infections among adolescents: a clash of ideology
      and science.

PMID- 9605905
TI  - Reconsideration of rifampin: a unique drug for a unique infection.

PMID- 9605906
TI  - Pediatrics on the PC.

PMID- 9605908
TI  - Another letter to the president.

PMID- 9605909
TI  - Decrease in ventilation time with a standardized weaning process.
AB  - OBJECTIVE: To test the hypothesis that standardizing the process of weaning from
      mechanical ventilation would decrease ventilation times and length of stay in a
      surgical intensive care unit. DESIGN: Comparison of historic ventilation times
      with physician-directed weaning with those obtained with protocol-guided weaning
      by respiratory therapists. SETTING: Urban, teaching surgical intensive care unit
      with open admission policy and no dominant diagnosis related group. RESULTS: From
      January 1, 1995, through December 31, 1995, 378 patients who underwent physician
      directed weaning from a ventilator had 64488 hours of ventilation, compared with
      57796 ventilation hours in 515 patients with protocol-guided weaning (April 1,
      1996, through May 31, 1997). The mean hours of ventilation decreased by 58 hours,
      a 46% decrease (P<.001). The length of hospital stay decreased by 1.77 days (29%
      change), while the Acute Physiology and Chronic Health Evaluation III score
      remained at 50 to 51. The number of reintubations did not change. The marginal
      cost savings was $603580. CONCLUSION: Protocol-guided weaning from mechanical
      ventilation leads to more rapid extubation than physician-directed weaning and
      has great potential for cost savings.

PMID- 9605910
TI  - Intestinal atresia and stenosis: a 25-year experience with 277 cases.
AB  - OBJECTIVE: To evaluate the causes, clinical presentation, diagnosis, operative
      management, postoperative care, and outcome in infants with intestinal atresia.
      DESIGN: Retrospective case series. SETTING: Pediatric tertiary care teaching
      hospital. PATIENTS: A population-based sample of 277 neonates with intestinal
      atresia and stenosis treated from July 1, 1972, through April 30, 1997. The level
      of obstruction was duodenal in 138 infants, jejunoileal in 128, and colonic in
      21. Of the 277 neonates, 10 had obstruction in more than 1 site. Duodenal atresia
      was associated with prematurity (46%), maternal polyhydramnios (33%), Down
      syndrome (24%), annular pancreas (33%), and malrotation (28%). Jejunoileal
      atresia was associated with intrauterine volvulus, (27%), gastroschisis (16%),
      and meconium ileus (11.7%). INTERVENTIONS: Patients with duodenal obstruction
      were treated by duodenoduodenostomy in 119 (86%), of 138 patients duodenotomy
      with web excision in 9 (7%), and duodenojejunostomy in 7 (5%) A duodenostomy tube
      was placed in 3 critically ill neonates. Patients with jejunoileal atresia were
      treated with resection in 97 (76%) of 128 patients (anastomosis, 45 [46%];
      tapering enteroplasty, 23 [24%]; or temporary ostomy, 29 [30%]), ostomy alone in
      25 (20%), web excision in 5 (4%), and the Bianchi procedure in 1 (0.8%). Patients
      with colon atresia were managed with initial ostomy and delayed anastomosis in 18
      (86%) of 21 patients and resection with primary anastomosis in 3 (14%). Short
      bowel syndrome was noted in 32 neonates. MAIN OUTCOME MEASURES: Morbidity and
      early and late mortality. RESULTS: Operative mortality for neonates with duodenal
      atresia was 4%, with jejunoileal atresia, 0.8%, and with colonic atresia, 0%. The
      long-term survival rate for children with duodenal atresia was 86%; with
      jejunoileal atresia, 84%; and with colon atresia, 100%. The Bianchi procedure (1
      patient, 0.8%) and growth hormone, glutamine, and modified diet (4 patients, 1%)
      reduced total parenteral nutrition dependence. CONCLUSIONS: Cardiac anomalies
      (with duodenal atresia) and ultrashort-bowel syndrome (<40 cm) requiring long
      term total parenteral nutrition, which can be complicated by liver disease (with
      jejunoileal atresia), are the major causes of morbidity and mortality in these
      patients. Use of growth factors to enhance adaptation and advances in small bowel
      transplantation may improve long-term outcomes.

PMID- 9605911
TI  - Improved survival in congenital diaphragmatic hernia with evolving therapeutic
      strategies.
AB  - OBJECTIVE: To compare the survival rates for 3 therapeutic eras, each using
      different treatment strategies for the management of newborns with congenital
      diaphragmatic hernia (CDH). DESIGN: Retrospective review of all infants with CDH
      from 1970 through 1997. SETTING: Tertiary care children's hospital. PARTICIPANTS:
      A total of 203 newborns with CDH. INTERVENTIONS: Extracorporeal membrane
      oxygenation (ECMO) was performed with arterial and venous cannulation connected
      to a membrane oxygenatorroller pump perfusion apparatus, using systemic
      heparinization. Delayed operative therapy involved operative repair 2 to 5 days
      after birth using preoperative ventilation support only. Since 1970, 203 newborns
      with CDH were managed in 3 therapeutic eras: era 1 (1970-1983, 102 patients) was
      immediate CDH repair with postoperative ventilator and pharmacologic support; era
      2 (1984-1988, 45 patients) was immediate repair with postoperative ventilator
      support (18 patients), immediate ECMO with CDH repair on ECMO (4 patients), or
      immediate repair with postoperative ECMO (23 patients); and era 3 (1989-1997, 56
      patients) was immediate ECMO with repair on ECMO (23 patients), immediate repair
      with postoperative ECMO (9 patients), or delayed (2-5 days) CDH repair (24
      patients). MAIN OUTCOME MEASURES: Survival, defined as discharge from the
      hospital, and morbidity. RESULTS: Survival was 42% (43/102 patients) in era 1,
      58% (26/45 patients) in era 2, and 79% (44/56 patients) in era 3 (P<.02 vs eras 1
      and 2). In era 3, the survival for immediate ECMO with repair on ECMO was 57%
      (13/23 patients), 89% (8/9 patients) for immediate repair with postoperative
      ECMO, and 96% (23/24 patients) for delayed repair. Eight late deaths were caused
      by pulmonary hypertension (1 death), sudden infant death syndrome (1 death), and
      other causes (6 deaths). Morbidity in survivors included mild neurologic deficit
      (5 patients) and pulmonary disease (3 patients). CONCLUSION: These data
      demonstrate a significant improvement in survival in CDH with preoperative ECMO
      and with delayed repair with and without ECMO support and suggest that immediate
      repair of CDH without the availability of ECMO support should be abandoned.

PMID- 9605912
TI  - A prospective analysis of office-based breast ultrasound.
AB  - OBJECTIVE: To determine the usefulness of office-based breast ultrasound. DESIGN:
      Prospective, nonrandomized study. SETTING: Academic-affiliated community teaching
      hospital. PATIENTS: Among 653 consecutive patients seen in our office during a 30
      month period, we performed 660 ultrasound examinations. The presenting complaint
      included a palpable mass in 53%, abnormal mammogram in 39%, and nipple discharge
      or retraction in 3%. INTERVENTION: Ultrasound examination was performed using a
      handheld 7.5-MHz linear array transducer. Findings and pertinent
      clinicopathologic data were recorded prospectively in our Breast Ultrasound
      Registry. MAIN OUTCOME MEASURE: Contribution of breast ultrasound to diagnosis
      and treatment. RESULTS: The sonogram was normal in 201 cases (30%), showed duct
      ectasia in 20 cases (3%), a simple cyst or seroma in 101 cases (15%), and a focal
      complex or solid abnormality in 338 cases (51%). Among the last group, 114 (97%)
      of 118 lesions thought to be benign on ultrasonography proved to be benign,
      whereas 13 (12%) of 111 indeterminate and 72 (75%) of 96 sonographically
      suspicious lesions proved to be cancer (including 13 cases with normal
      mammograms). Ultrasonographic features of malignancy included an anteroposterior
      to-lateral dimension ratio of 1 or greater, heterogeneous hypoechoicity,
      irregular shadowing, and fuzzy and/or jagged margins. Ultrasound-guided needle
      biopsy accurately diagnosed 46 benign nonpalpable lesions and 20 malignant
      nonpalpable lesions. CONCLUSIONS: These data suggest that ultrasonography is a
      useful adjunct to clinical and mammographic evaluation of breast disease. Breast
      ultrasound identifies cysts, aids in differentiating benign from malignant
      lesions, and facilitates office needle biopsy of nonpalpable abnormalities,
      permitting timely and cost-effective patient care.

PMID- 9605913
TI  - Evaluation of benign vs malignant hepatic lesions with positron emission
      tomography.
AB  - BACKGROUND: In most malignant cells, the relatively low level of glucose-6
      phosphatase leads to accumulation and trapping of [18F]fluorodeoxyglucose (FDG)
      intracellularly, allowing the visualization of increased uptake compared with
      normal cells. OBJECTIVES: To assess the value of FDG positron emission tomography
      (PET) to differentiate benign from malignant hepatic lesions and to determine in
      which types of hepatic tumors PET can help evaluate stage, monitor response to
      therapy, and detect recurrence. DESIGN: Prospective blinded-comparison clinical
      cohort study. SETTING: Tertiary care university hospital and clinic. PATIENTS:
      One hundred ten consecutive referred patients with hepatic lesions 1 cm or larger
      on screening computed tomographic (CT) images who were seen for evaluation and
      potential resection underwent PET imaging. There were 60 men and 50 women with a
      mean (+/-SD) age of 59 +/- 14 years. Follow-up was 100%. INTERVENTIONS: A PET
      scan using static imaging was performed on all patients. The PET scan imaging and
      biopsy, surgery, or both were performed, providing pathological samples within 2
      months of PET imaging. All PET images were correlated with CT scan to localize
      the lesion. However, PET investigators were unaware of any previous
      interpretation of the CT scan. MAIN OUTCOME MEASURES: Visual interpretation,
      lesion-to-normal liver background (L/B) ratio of radioactivity, and standard
      uptake value (SUV) were correlated with pathological diagnosis. RESULTS: All
      (100%) liver metastases from adenocarcinoma and sarcoma primaries in 66 patients
      and all cholangiocarcinomas in 8 patients had increased uptake values, L/B ratios
      greater than 2, and an SUV greater than 3.5. Hepatocellular carcinoma had
      increased FDG uptake in 16 of 23 patients and poor uptake in 7 patients. All
      benign hepatic lesions (n = 23), including adenoma and fibronodular hyperplasia,
      had poor uptake, an L/B ratio of less than 2, and an SUV less than 3.5, except
      for 1 of 3 abscesses that had definite uptake. CONCLUSIONS: The PET technique
      using FDG static imaging was useful to differentiate malignant from benign
      lesions in the liver. Limitations include false-positive results in a minority of
      abscesses and false-negative results in a minority of hepatocellular carcinoma.
      The PET technique was useful in tumor staging and detection of recurrence, as
      well as monitoring response to therapy for all adenocarcinomas and sarcomas and
      most hepatocellular carcinomas. Therefore, pretherapy PET imaging is recommended
      to help assess new hepatic lesions.

PMID- 9605914
TI  - Comparison of laparoscopic and open staging in Hodgkin disease.
AB  - BACKGROUND: Staging laparotomy provides useful information for management of
      Hodgkin disease but has fallen into disfavor because procedure-related morbidity
      exceeds that of new chemotherapeutic regimens. OBJECTIVE: To determine the
      feasibility, effectiveness, and safety of laparoscopic staging for Hodgkin
      disease compared with those of open staging. PATIENTS: Fifty-five patients with
      Hodgkin disease of cell types including nodular sclerosis in 43 (78%), mixed
      cellularity in 9 (16%), and lymphocyte predominance in 3 (5%). STUDY DESIGN:
      Concurrent evaluation of laparoscopic staging (n = 15) and retrospective review
      of open staging (n = 40). INTERVENTIONS: Laparoscopic and open techniques of
      surgical staging for Hodgkin disease, including splenectomy, liver biopsies, and
      lymph node sampling. MAIN OUTCOME MEASURES: Operative time, duration of
      postoperative ileus and of postoperative hospitalization, morbidity, number of
      lymph nodes retrieved, alteration in pathologic stage, recurrence, and survival.
      RESULTS: For laparoscopic staging vs open staging groups, mean operative time was
      202 vs 144 minutes (P=.001); mean postoperative ileus was 1.9 vs 3.2 days
      (P<.001); mean postoperative hospitalization was 4.4 vs 6.7 days (P<.001);
      complications occurred in 3 patients (20%) vs 11 patients (28%) (P=.57); and mean
      number of lymph nodes retrieved was 8.5 vs 4.6 (P=.05). In the laparoscopic
      staging group, 2 cases (13%) were upstaged and 2 cases (13%) were downstaged. In
      the open staging group, 6 cases (15%) were upstaged and 3 cases (7.5%) were
      downstaged. Follow-up data were available for all patients in the laparoscopic
      staging group, at a mean of 23.5 months postoperatively. All were alive, none had
      recurrent disease below the diaphragm, and 2 (13%) had residual mediastinal
      disease. Follow-up data were available for 31 patients (78%) in the open staging
      group at a mean of 52.5 months postoperatively. All were alive, 27 (87%) were
      disease free, 3 (10%) had had relapses above the diaphragm, and 1 (3%) had
      residual mediastinal disease. CONCLUSIONS: Compared with open staging,
      laparoscopic staging of Hodgkin disease is oncologically equivalent and
      functionally superior. These data should encourage reappraisal of the role of
      operative staging in the management of Hodgkin disease.

PMID- 9605915
TI  - Treatment of advanced gastroesophageal reflux disease with Collis gastroplasty
      and Belsey partial fundoplication.
AB  - OBJECTIVE: To examine the factors affecting outcome in patients with advanced
      gastroesophageal reflux disease. DESIGN: Retrospective analysis. SETTING:
      University tertiary referral center. PATIENTS: Thirty-seven patients with
      advanced gastroesophageal reflux disease and no previous antireflux surgery.
      INTERVENTIONS: Thirty patients underwent Collis gastroplasty for esophageal
      lengthening and Belsey partial fundoplication. Seven patients with esophageal
      stricture and global loss of esophageal body motility who underwent primary
      esophagectomy and reconstruction were used as a comparison group. OUTCOME
      MEASURES: Symptomatic outcome in all 37 patients was assessed by questionnaire at
      a median of 25 months (range, 5-156 months) after surgery. In a subset of 11
      patients undergoing the Collis-Belsey procedure, outcome was measured using 24
      hour pH and results of motility studies. RESULTS: The Collis-Belsey procedure was
      successful in relieving symptoms of gastroesophageal reflux in 21 (70%) of the 30
      patients. The outcome was excellent or good in 16 (89%) of 18 patients who
      presented with symptoms other than dysphagia, but only in 5 (42%) of 12 patients
      with dysphagia (P = .01). The outcome was particularly poor if dysphagia was
      associated with a previously dilated esophageal stricture. Persistent or induced
      dysphagia was the reason for failure in all but 1 patient. Results of 24-hour
      esophageal pH studies were returned to normal in 8 (73%) of 11 patients
      undergoing postoperative evaluation. Contraction amplitudes in the distal
      esophagus and the prevalence of simultaneous contractions in these segments did
      not change after the operation. All 7 patients who underwent primary
      esophagectomy were classified as having an excellent or good outcome and were
      relieved of their reflux symptoms, including dysphagia. Six of these could eat 3
      meals per day and enjoyed an unrestricted diet. CONCLUSIONS: The outcome of the
      Collis-Belsey procedure in patients with advanced gastroesophageal reflux disease
      without dysphagia is excellent. It is less so in patients with dysphagia as a
      preoperative symptom. Esophagectomy can provide a good outcome in patients who
      have a combination of dysphagia stricture and a profound loss of esophageal
      motility.

PMID- 9605916
TI  - Institutional learning curve of surgeon-performed trauma ultrasound.
AB  - BACKGROUND: Sonography has become the primary mode for the initial evaluation of
      abdominal injury in many trauma centers. However, the rate at which
      nonradiologists become proficient in this technique remains controversial.
      OBJECTIVE: To assess the learning curve for this technique in a single
      institution. DESIGN: Retrospective review of sonographic examinations for trauma
      performed by senior surgical residents during a 24-month period at an American
      College of Surgeons-verified level I trauma center. SETTING: University
      affiliated private hospital. PATIENTS AND METHODS: Before the initiation of a
      program of surgeon-performed trauma ultrasound, senior surgical residents
      (postgraduate years 4 and 5) received 11.5 hours of hands-on and didactic
      instruction in the focused ultrasound examination for trauma. This examination
      then became a standard component of the evaluation of injured patients.
      Subsequent groups of senior residents received 8 hours of instruction at the
      onset of new academic years, 6 and 18 months, respectively, after the initial
      course. The sensitivity, specificity, accuracy, positive predictive value, and
      negative predictive value were then calculated for each 6-month period after the
      introduction of trauma sonography. RESULTS: During the 24-month study period, 902
      sonographic examinations were performed. No statistically significant differences
      were noted in sensitivity, specificity, accuracy, positive predictive value, or
      negative predictive value for any 6-month period of study when compared with the
      other 6-month periods or with the values calculated for the entire study period.
      CONCLUSIONS: Senior surgical residents are capable of performing the focused
      ultrasound examination for trauma with a high level of skill after a concise
      introductory course. A learning curve was not apparent in our series. Criteria
      for being permitted to perform trauma sonography that include the requirement of
      a large number of examinations or extensive proctoring should be reassessed.

PMID- 9605917
TI  - Tracheostomy in the young pediatric burn patient.
AB  - OBJECTIVE: To evaluate the incidence of complications in comparison with the
      benefits of tracheostomy in young pediatric burn patients (newborn to 3 years
      old). DESIGN: Retrospective survey. SETTING: Tertiary care burn center. PATIENTS:
      A total of 1549 consecutive pediatric burn patients, of whom 180 were intubated.
      INTERVENTIONS: Tracheostomy was performed in 76 children. MAIN OUTCOME MEASURES:
      Duration of mechanical ventilation, mortality, respiratory complications, airway
      complications, and condition of the airway at discharge from the hospital.
      RESULTS: Seventy-six patients required tracheostomy. Their mean burn size was 34%
      total body surface area and mean length of stay in the hospital was 56 days.
      There were no perioperative complications. Eight patients (10%) could not be
      decannulated because of airway obstruction. Five of these outgrew their
      obstruction, 2 required surgery, and 1 continues to be evaluated for laryngeal
      reconstruction. CONCLUSION: Pediatric tracheostomy can be performed safely with
      no perioperative complications and acceptable chronic morbidity.

PMID- 9605918
TI  - Corticotropin-independent macronodular adrenal hyperplasia: a clinicopathologic
      correlation.
AB  - OBJECTIVES: To investigate the clinical presentation, laboratory findings, and
      pathologic characteristics of patients with corticotropin (ACTH)-independent
      macronodular adrenal hyperplasia. DESIGN: Retrospective review. SETTING: Academic
      medical center. PATIENTS: All patients with bilateral adrenocortical nodules
      associated with ACTH-independent hypercortisolism without clinicopathologic
      features of primary pigmented nodular adrenocortical disease with atrophic
      internodular adrenal cortex. MAIN OUTCOME MEASURES: Compare and contrast our
      findings with those previously reported; assess response to adrenalectomy.
      RESULTS: Nine patients met the criteria for corticotropin-independent
      macronodular adrenal hyperplasia. All patients had biochemical evidence of
      Cushing syndrome, although repetitive testing was frequently required. As a
      result, the diagnosis was delayed from 1 to 20 years. In all patients, both the
      low- and high-dose dexamethasone suppression tests failed to suppress cortisol
      secretion. No patient had elevated ACTH levels, and following curative bilateral
      adrenalectomy, no patient subsequently developed Nelson syndrome, with follow-up
      ranging from 1 to 8.5 years. Unique histologic features were identified in all
      cases. CONCLUSION: Amalgamating this series with other clinical reports plus
      basic research information, corticotropin-independent macronodular adrenal
      hyperplasia must be considered a separate and legitimate cause of Cushing
      syndrome.

PMID- 9605919
TI  - A critical reappraisal of indications for fasciotomy after extremity vascular
      trauma.
AB  - OBJECTIVE: To critically reevaluate the indications for fasciotomy in vascular
      trauma of the extremities. DESIGN: Case-control study. SETTING: Level I trauma
      center. MATERIALS AND METHODS: One hundred sixty-three vascular injuries to the
      extremeties were analyzed. Fasciotomy as an adjunct to vascular repair was
      performed in 45 limbs (28%), based either on the nature of injury or measured
      compartment pressure of greater than 35 mm Hg. MAIN OUTCOME MEASURES: Need for
      fasciotomy or limb amputation. RESULTS: Fasciotomy was performed for 29.5% of
      isolated arterial injuries, 15.2% of isolated venous injuries, and 31.6% of
      combined arterial and venous injuries, and was not related to venous repair or
      ligation. Seven delayed fasciotomies were performed either for vascular repair
      failure (5 patients) or compartment syndrome (2 patients). The highest incidence
      was for popliteal vessel injury (arterial 57%, combined 61%). Of the 33 lower
      extremity fasciotomies, 58% were for popliteal vessel injury. In 51 combined
      injuries of the lower extremity, only 7 (19%) of 38 patients with injury above
      the knee required fasciotomy, as compared with 8 (62%) of 13 with injury to the
      popliteal vessels (P<.001), with or without venous repair. There were 3
      amputations, all resulting from vascular repair failure. CONCLUSIONS: The
      presence of a combined vascular injury or the need for venous ligation does not
      necessitate routine fasciotomy. The need for fasciotomy may be maximal for
      injuries to popliteal vessels.

PMID- 9605920
TI  - Delayed primary repair of esophageal atresia with tracheoesophageal fistula: is
      it worth the wait?
AB  - OBJECTIVE: To characterize a successful approach to the management of infants
      with long-gap esophageal atresia (EA) with tracheoesophageal fistula (TEF),
      significant prematurity with respiratory distress syndrome (RDS), or both, so as
      to preserve the native esophagus. DESIGN: A review of the medical records and
      office charts of a cohort of patients with EA and TEF. SETTING: A tertiary care
      children's hospital affiliated with a major university. PATIENTS: A total of 118
      children with EA and TEF admitted from February 1986 through December 1996. All
      of the patients diagnosed as having EA and TEF during this period were included.
      INTERVENTION: Of the 118 infants, 88 received primary repair of EA and TEF within
      48 hours of birth. An additional 23 children had the TEF divided and a
      gastrostomy placed secondary to (1) severe RDS and prematurity (n = 6), (2) long
      gap EA (gap length > 4 cm or the upper pouch above the thoracic inlet (n = 10),
      or (3) associated cardiac defects (n = 7). Delayed primary EA repair was done
      when the RDS resolved or the gap length was 2 cm or less. MAIN OUTCOME MEASURES:
      Successful anastomosis of native esophagus. Comparison of incidence of
      gastroesophageal reflux, anastomotic complications, or survival between groups
      undergoing primary or delayed repair. RESULTS: Primary EA was accomplished in 88
      patients. Delayed EA was successfully accomplished in 18 of the 19 surviving
      patients within 5 months, thereby preserving the native esophagus in all
      surviving infants. There was no difference in anastomotic complications,
      gastroesophageal reflux, or survival when the delayed group was compared with
      those who had a primary repair. CONCLUSIONS: Using delayed EA repair, all
      children with EA and TEF, regardless of gap length, can have their esophagus
      preserved. The primary cause of mortality was the association of a severe cardiac
      anomaly with EA and TEF.

PMID- 9605921
TI  - Revisiting the role of tumor necrosis factor alpha and the response to surgical
      injury and inflammation.
AB  - Tumor necrosis factor alpha (TNF-alpha) is a pleiotropic cytokine with diverse
      biological actions. Studies originally identified TNF-alpha as a systemic
      mediator of endotoxemic shock, cachexia, and tumor regression. We now recognize
      that TNF-alpha is a member of a large family of proteins, including Fas ligand,
      whose actions are primarily paracrine in nature, and serve to regulate both cell
      proliferation and apoptotic death. Although clinical trials with TNF-alpha
      inhibitors in sepsis syndrome have been disappointing to date, and TNF-alpha
      administration has not proven widely successful as an antineoplastic agent,
      preliminary successes with TNF-alpha inhibition have been recently reported in
      more chronic inflammatory diseases, including rheumatoid arthritis and ulcerative
      colitis. The recent description of the TNF-alpha converting enzyme responsible
      for the processing of cell-associated to secreted TNF-alpha has opened a new
      therapeutic avenue to address inflammatory diseases dependent on the release of
      17-kd secreted TNF-alpha. Similarly, inhibitors of nuclear factor kappa B
      activation can increase TNF-alpha-mediated apoptosis and have rejuvenated efforts
      to explore TNF-alpha's antineoplastic potential. The multiple and often
      conflicting TNF-alpha signaling pathways reveal a diversity to TNF-alpha's
      actions not fully appreciated in the past. Such investigations have opened a
      number of novel therapeutic interventions to either inhibit or potentiate the
      actions of TNF-alpha during surgical injury or acute inflammation.

PMID- 9605922
TI  - General and gastrointestinal tract surgery in France.
AB  - Forty-three state-run medical schools admit 30000 students per year but only 3500
      receive their diploma after 6 years of studies. After passing a special
      examination, 480 of 2000 residents choose surgery and train during twelve 6-month
      rotations. Surgical research is organized through government agencies, individual
      units, or volunteer groups. In 1992, of 8268114 procedures, appendectomy
      represented 4.15%; hernia, 4.09%; varicose veins, 3.61%; and cholecystectomy,
      1.82%. Appendectomy has decreased from 306500 per year in 1980 (34% of all
      gastrointestinal surgical procedures) to 159900 (15%) in 1996, whereas
      cholecystectomy has increased from 64700 to 95300. Emergency gastrointestinal
      procedures represented 15% of all surgical procedures in 1996, doubling in the
      last 4 years (essentially for labor and endoscopic procedures). Ambulatory
      procedures have increased 12-fold since 1980, essentially (75%) in private
      practice. About 27% of 160000 appendectomies and 77% of 95300 cholecystectomies
      were performed laparoscopically in 1997. One person of 4 in France has or has had
      cancer, mainly due to tobacco abuse. In 1993, 32000 surgical procedures were
      performed for gastrointestinal cancer. Of 532000 deaths (1992), about 150000 were
      due to cancer, 10000 to alcohol-related disease, and 22000 to trauma.
      Transplantation in France increased from 3180 procedures in 1993 to 2807 in 1996,
      essentially lungs and heart and lungs. Between 60% and 100% of health
      expenditures are reimbursed by the government, the remaining being covered by
      private insurances. Approximately 60% of 4500 French surgeons are in private
      practice; 25% also have part-time hospital employment. Almost 40% of surgeons
      work full-time in hospitals.

PMID- 9605923
TI  - Joseph Pancoast's A treatise on operative surgery.

PMID- 9605924
TI  - A novel TR beta mutation (R383H) in resistance to thyroid hormone syndrome
      predominantly impairs corepressor release and negative transcriptional
      regulation.
AB  - Resistance to thyroid hormone (RTH) is characterized by elevated serum thyroid
      hormones, failure to suppress pituitary TSH secretion, and variable T3
      responsiveness in peripheral tissues. The disorder is associated with diverse
      mutations that cluster within three areas of the thyroid hormone beta(TR beta)
      receptor. Here, we report a novel RTH mutation (R383H), which is located in a
      region not known to harbor naturally occurring mutations. Although the R383H
      mutant receptor activated positively regulated genes to an extent comparable to
      wild-type (WT), negative transcriptional regulation of human TSH alpha and TRH
      promoters was impaired in either TR beta 1 or TR beta 2 contexts, and WT receptor
      function was dominantly inhibited. T3-dependent changes in basal transcription
      with R383H were also impaired: on the TRH promoter, basal activation by
      unliganded R383H was not reversed by T3 to the same extent as WT; similarly
      transcriptional silencing by an unliganded Gal4-R383H fusion was not relieved at
      a T3 concentration that derepressed WT. In keeping with this, ligand-dependent
      corepressor release by R383H, either in a protein-protein interaction assay or as
      a DNA-bound heterodimer with retinoid X receptor on either positive or negative
      thyroid hormone response elements, was disproportionately impaired relative to
      its ligand-binding affinity, whereas its T3-dependent recruitment of coactivator
      was unimpaired. These properties were shared by another previously described RTH
      mutant (R429Q), and in the crystal structure of TR alpha the homologous residues
      interact in a polar invagination. Our data indicate a role for these residues in
      mediating negative transcriptional regulation and facilitating corepressor
      release and suggest that predominant impairment of these functions may be the
      minimal requirements for causation of RTH.

PMID- 9605925
TI  - Cell-specific expression of the mouse glycoprotein hormone alpha-subunit gene
      requires multiple interacting DNA elements in transgenic mice and cultured cells.
AB  - The glycoprotein hormone alpha-subunit gene is expressed and differentially
      regulated in pituitary gonadotropes and thyrotropes. Previous gene expression
      studies suggested that cell specificity may be regulated by distinct DNA
      elements. We have identified an enhancer region between -4.6 and -3.7 kb that is
      critical for high level expression in both gonadotrope and thyrotrope cells of
      transgenic mice. Fusion of the enhancer to -341/+43 mouse alpha-subunit promoter
      results in appropriate pituitary cell specificity and transgene expression levels
      that are similar to levels observed with the intact -4.6 kb/+43 construct.
      Deletion of sequences between -341 and -297 resuited in a loss of high level
      expression and cell specificity, exhibited by ectopic transgene activation in GH
      , ACTH-, and PRL-producing pituitary cells as well as in other peripheral
      tissues. Consistent with these results, transient cell transfection studies
      demonstrated that the enhancer stimulated activity of a -341/+43 alpha-promoter
      in both alphaTSH and alphaT3 cells, but it did not enhance alpha-promoter
      activity significantly in CV-1 cells. Removal of sequences between -341 and -297
      allowed the enhancer to function in heterologous cells. Loss of high level
      expression and cell specificity may be due to loss of sequences required for
      binding of the LIM homeoproteins or the alpha-basal element 1. These data
      demonstrate that the enhancer requires participation by both proximal and distal
      sequences for high level expression and suggests that sequences from -341 to -297
      are critical for restricting expression to the anterior pituitary.

PMID- 9605926
TI  - Agonist-induced phosphorylation of the endogenous AT1 angiotensin receptor in
      bovine adrenal glomerulosa cells.
AB  - A polyclonal antibody was raised in rabbits against a fusion protein immunogen
      consisting of bacterial maltose-binding protein coupled to a 92-amino acid C
      terminal fragment of the rat AT1b angiotensin II (Ang II) receptor. The antibody
      immunoprecipitated the photoaffinity-labeled bovine AT1 receptor (AT1-R), but not
      the rat AT2 receptor, and specifically stained bovine adrenal glomerulosa cells
      and AT1a receptor-expressing Cos-7 cells, as well as the rat adrenal zona
      glomerulosa and renal glomeruli. The antibody was employed to analyze Ang II
      induced phosphorylation of the endogenous AT1-R immunoprecipitated from cultured
      bovine adrenal glomerulosa cells. Receptor phosphorylation was rapid, sustained
      for up to 60 min, and enhanced by pretreatment of the cells with okadaic acid.
      Its magnitude was correlated with the degree of ligand occupancy of the receptor.
      Activation of protein kinase A and protein kinase C (PKC) also caused
      phosphorylation of the receptor, but to a lesser extent than Ang II. Inhibition
      of PKC by staurosporine augmented Ang II-stimulated AT1-R phosphorylation,
      suggesting a negative regulatory role of PKC on the putative G protein-coupled
      receptor kinase(s) that mediates the majority of AT1-R phosphorylation. The
      antibody should permit further analysis of endogenous AT1-R phosphorylation in
      Ang II target cells.

PMID- 9605927
TI  - Requirements for repression of retinoid X receptor by the oncoprotein P75gag-v
      erbA and the thyroid hormone receptors.
AB  - The oncogenic counterpart of thyroid hormone receptor-alpha (TRRalpha), denoted
      P75gag-v-erbA, has served as a paradigm for the ability of TRs to repress basal
      levels of transcription. We show here that the retinoid X receptor (RXR), when
      activated by its specific ligand SR11237, is repressed by both the normal TRalpha
      and the P75gag-v-erbA. The repression caused by the two proteins is distinct and
      dependent on both the cell type and the hormone-response element through which
      RXR acts. In HeLa cells only TR repressed efficiently through the palindromic
      2xIR0 element, whereas the proteins were equally efficient in JEG cells. This
      demonstrates that proteins distinct in the two cell types mediate the repression.
      RXR-dependent induction via the natural response element of the cellular retinol
      binding protein (CRBPII) gene was likewise (> or = 50%) repressed by TR, whereas
      P75gag-v-erbA did not repress during the same conditions. Furthermore, P75gag-v
      erbA and its variants v-erbAtd359 (lacking repressing activity on TR) and v
      erbAr12 (a highly active repressor of TR) efficiently repressed induction by a
      hybrid protein consisting of the DNA- binding domain of Gal4 and the ligand
      binding region of RXR. The viral proteins did not, however, associate with RXR
      unless the two partners were allowed to heterodimerize upon binding to a specific
      response element, such as the 2xIR0 element or that of the CRBPII gene. In
      conclusion, we suggest that the efficient repression seen with the the 2xIR0
      element is due to heterodimerization of TR or the viral oncoproteins with RXR and
      a concomitant inhibition of binding of the RXR-specific ligand that results in an
      inability of RXR to attract a cell type-specific cofactor. In addition, the data
      suggest that the interaction between RXR and P75gag-v-erbA on the CRBPII element
      is too weak to inhibit RXR from binding a ligand and therefore also to repress.

PMID- 9605928
TI  - Functional activities of the A and B forms of the human androgen receptor in
      response to androgen receptor agonists and antagonists.
AB  - The androgen receptor (AR) is present in many cells in two forms. The B form
      migrates with an apparent mass of 110 kDa and constitutes more than 80% of the
      immunoreactive receptor in most cell types. The A form of the AR migrates with an
      apparent mass of 87 kDa, appears to derive from internal translation initiation
      at methionine-188 in the AR open-reading frame, and usually constitutes 20% or
      less of the immunoreactive AR present. Previous experiments designed to examine
      the functional capacity of the A and B forms of the AR have been hampered by
      marked differences in the expression levels of the two isoforms, as the
      nucleotide sequence surrounding the codon encoding methionine-188 causes it to be
      used inefficiently as a translation initiation site. To circumvent this, we
      altered the nucleotide sequence surrounding methionine-188 to render it more
      similar to that surrounding the codon encoding methionine-1. Transfection of a
      cDNA containing these changes resulted in similar levels of expression of A and B
      forms of the AR as assessed by immunoblot assays using antibodies directed at an
      epitope preserved in both. Functional activities of these cDNAs were assessed
      using cotransfection assays that employed two model androgen-responsive genes
      (MMTV-luciferase and PRE2-tk-luciferase) in response to mibolerone, a potent
      androgen agonist, in three different cell lines. These studies demonstrated
      subtle differences in the activities of the A and B isoforms, which depended on
      the promoter and cell context. Additional studies failed to reveal any major
      differences in the responses of the AR-A and AR-B isoforms to a variety of
      androgen agonists and antagonists, suggesting that the previously reported
      functional defect of the AR-A is due principally to its level of expression. When
      assays of AR function are performed under conditions in which levels of
      expression of the two isoforms are equivalent, the AR-A and AR-B possess similar
      functional activities.

PMID- 9605929
TI  - The high mobility group protein 1 enhances binding of the estrogen receptor DNA
      binding domain to the estrogen response element.
AB  - We have examined the ability of the high-mobility group protein 1 (HMG1) to alter
      binding of the estrogen receptor DNA-binding domain (DBD) to the estrogen
      response element (ERE). HMG1 dramatically enhanced binding of purified,
      bacterially expressed DBD to the consensus vitellogenin A2 ERE in a dose
      dependent manner. The ability of HMG1 to stabilize the DBD-ERE complex resulted
      in part from a decrease in the dissociation rate of the DBD from the ERE.
      Antibody supershift experiments demonstrated that HMG1 was also capable of
      forming a ternary complex with the ERE-bound DBD in the presence of HMG1-specific
      antibody. HMG1 did not substantially affect DBD-ERE contacts as assessed by
      methylation interference assays, nor did it alter the ability of the DBD to
      induce distortion in ERE-containing DNA fragments. Because HMG1 dramatically
      enhanced estrogen receptor DBD binding to the ERE, and the DBD is the most highly
      conserved region among the nuclear receptor superfamily members, HMG1 may
      function to enhance binding of other nuclear receptors to their respective
      response elements and act in concert with coactivator proteins to regulate
      expression of hormone-responsive genes.

PMID- 9605930
TI  - Binding of STAT5a and STAT5b to a single element resembling a gamma-interferon
      activated sequence mediates the growth hormone induction of the mouse acid-labile
      subunit promoter in liver cells.
AB  - After birth, the endocrine actions of insulin-like growth factor (IGF)-I and -II
      become increasingly important. In postnatal animals, most of circulating IGFs
      occur in 150-kDa complexes formed by association of an acid-labile subunit (ALS)
      with complexes of IGF and IGF-binding protein-3. ALS is synthesized almost
      exclusively in liver. GH stimulates the transcription of the ALS gene, resulting
      in increased hepatic mRNA and circulating ALS levels. To map the GH response
      element, a series of 5'-deletion fragments of the mouse ALS promoter (nt -2001 to
      -49, A(+1)TG) were inserted in the luciferase reporter plasmid pGL3 and
      transfected into the H4-II-E rat hepatoma cell line. GH stimulated the activity
      of promoter fragments with 5'-ends between nucleotide (nt) -2001 and nt -653 by
      1.9- to 2.7-fold. This stimulation was abolished by deletion of the region
      located between nt -653 and nt -483. This region contains two sites, ALS-GAS1 and
      ALS-GAS2, that resemble the gamma-interferon activated sequence (GAS). Mutation
      of the ALS-GAS1 site, but not of the ALS-GAS2 site, eliminated the response to GH
      when assessed in the context of a GH-responsive promoter fragment, indicating
      that ALS-GAS1 was necessary for GH induction. Three tandem copies of ALS-GAS1
      were sufficient to confer GH inducibility to the minimal promoter of the
      thymidine kinase gene. In electrophoretic mobility shift assays, ALS-GAS1 formed
      a specific, GH-dependent protein-DNA complex with nuclear extracts from H4-II-E
      cells. Using antibodies directed against members of the family of signal
      transducers and activators of transcription (STAT), this complex was shown to be
      composed of STAT5a and STAT5b. Identical results were obtained when transfections
      and mobility shift assays were performed in primary rat hepatocytes in which the
      endogenous ALS gene is expressed. Thus, the transcriptional activation of the
      mouse ALS gene by GH is mediated by the binding of STAT5 isoforms to a single GAS
      like element.

PMID- 9605932
TI  - Transcriptional activation of the macrophage migration-inhibitory factor gene by
      the corticotropin-releasing factor is mediated by the cyclic adenosine 3',5'-
      monophosphate responsive element-binding protein CREB in pituitary cells.
AB  - Macrophage migration-inhibitory factor (MIF) has recently been identified as a
      pituitary hormone that functions as a counterregulatory modulator of
      glucocorticoid action within the immune system. In the anterior pituitary gland,
      MIF is expressed in TSH- and ACTH-producing cells, and its secretion is induced
      by CRF. To investigate MIF function and regulation within pituitary cells, we
      initiated the characterization of the MIF 5'-regulatory region of the gene. The 
      1033 to +63 bp of the murine MIF promoter was cloned 5' to a luciferase reporter
      gene and transiently transfected into freshly isolated rat anterior pituitary
      cells. This construct drove high basal transcriptional activity that was further
      enhanced after stimulation with CRF or with an activator of adenylate cyclase.
      These transcriptional effects were associated with a concomitant rise in ACTH
      secretion in the transfected cells and by an increase in MIF gene expression as
      assessed by Northern blot analysis. A cAMP-responsive element (CRE) was
      identified within the MIF promoter region which, once mutated, abolished the cAMP
      responsiveness of the gene. Using this newly identified CRE, DNA-binding activity
      was detected by gel retardation assay in nuclear extracts prepared from isolated
      anterior pituitary cells and AtT-20 corticotrope tumor cells. Supershift
      experiments using antibodies against the CRE-binding protein CREB, together with
      competition assays and the use of recombinant CREB, allowed the detection of CREB
      binding activity with the identified MIF CRE. These data demonstrate that CREB is
      the mediator of the CRF-induced MIF gene transcription in pituitary cells through
      an identified CRE in the proximal region of the MIF promoter.

PMID- 9605931
TI  - Insulin receptor substrate (IRS) proteins IRS-1 and IRS-2 differential signaling
      in the insulin/insulin-like growth factor-I pathways in fetal brown adipocytes.
AB  - In the present study we have investigated the contribution of the insulin
      receptor substrate proteins (IRS-1 and IRS-2) to the insulin/insulin like growth
      factor I (IGF-I)-signaling pathways in fetal rat brown adipocytes, a model that
      expresses both insulin and IGF-I receptors. Insulin/IGF-I rapidly stimulated IRS
      1 and IRS-2 tyrosine phosphorylation, their association with p85alpha, and IRS-1-
      and IRS-2-associated phosphatidylinositol (PI) 3-kinase activation to the same
      extent, the effect of insulin being stronger than the effect of IGF-I at the same
      physiological dose (10 nM). Furthermore, insulin/IGF-I stimulated IRS-1
      associated Grb-2 phosphorylation. However, IRS-2-associated Grb-2 phosphorylation
      was barely detected. Pull-down experiments with glutathione-S-transferase-fusion
      proteins containing SH2-domains of p85alpha revealed a strong association between
      IRS-1 and IRS-2 with p85alpha in response to insulin/IGF-I, the insulin effect
      being stronger than IGF-I. However, the Grb-2-SH2 domain showed functional
      differences. While a strong association between IRS-1/Grb-2 was found, IRS-2/Grb
      2 association was virtually absent in response to insulin/IGF-I, as also
      demonstrated in competition studies with a phosphopeptide containing the
      phosphotyrosine 895 residue within the putative Grb-2-binding domain. Finally,
      insulin/IGF-I stimulated tyrosine phosphorylation of the three SHC proteins (46,
      52, and 66 kDa). Moreover, insulin/IGF-I markedly increased the amount of Grb-2
      associated SHC proteins by the same extent. Our results suggest that both IRS-1
      and IRS-2 are required for phosphatidylinositol 3-kinase activation that leads to
      adipogenic and thermogenic differentiation of fetal brown adipose tissue;
      meanwhile, IRS-1 and SHC, but not IRS-2, associate with Grb-2 leading to the ras
      mitogen-activated protein kinase-signaling pathway required for fetal brown
      adipocyte proliferation.

PMID- 9605933
TI  - Transcription of the Leydig insulin-like gene is mediated by steroidogenic factor
      1.
AB  - The Leydig insulin-like gene (Ley I-L), a member of the insulin-related gene
      family, is specifically expressed in pre- and postnatal Leydig cells of the
      testis and in postnatal theca cells of the ovary. To determine the functional
      region of the mouse Ley I-L promoter and factors controlling the Ley I-L gene
      expression, we used 2.1 kb of the 5'-flanking region of the mouse Ley I-L gene to
      generate chimeric constructs with the chloramphenicol acetyltransferase gene
      (CAT). Transient transfections of MA10 Leydig cells, LTK- fibroblasts, and F9
      embryonic cells by a series of 5'-deleted mouse Ley I-L promoter-CAT constructs
      revealed that the sequence between nucleotides -157 to +4 directs the
      transcription of the reporter gene in MA10 but not in LTK- and F9 cells,
      indicating that the determinants of Leydig cell-specific expression reside within
      this region. Deoxyribonuclease I (DNase I) footprint analysis revealed that the
      sequences designated SF-1/1, SF-1/2, and SF-1/3 within three DNase I-protected
      regions are homologous to the consensus binding site of the steroidogenic factor
      1 (SF-1). Competition and antibody studies showed that the three SF-1-binding
      sites in the Ley I-L promoter have similar binding affinities for SF-1.
      Furthermore, transient transfections of MA10 cells with mutant reporter
      constructs, in which SF-1/1 or both SF-1/2 and SF-1/3 were deleted, demonstrated
      that all three SF-1-binding sites are required for SF-1-mediated stimulation of
      Ley I-L transcription. Cotransfection of an SF-1-containing expression vector
      together with a Ley I-L promoter-CAT construct into HeLa cells, which lack the
      endogenous SF-1 protein, resulted in CAT gene transcription, which indicated that
      SF-1 can transactivate the Ley I-L promoter. These data demonstrate an essential
      role of SF-1 in transcriptional activation of the Ley I-L promoter.

PMID- 9605934
TI  - The basic helix-loop-helix, leucine zipper transcription factor, USF (upstream
      stimulatory factor), is a key regulator of SF-1 (steroidogenic factor-1) gene
      expression in pituitary gonadotrope and steroidogenic cells.
AB  - Tissue-specific expression of the mammalian FTZ-F1 gene is essential for adrenal
      and gonadal development and sexual differentiation. The FTZ-F1 gene encodes an
      orphan nuclear receptor, termed SF-1 (steroidogenic factor-1) or Ad4BP, which is
      a primary transcriptional regulator of several hormone and steroidogenic enzyme
      genes that are critical for normal physiological function of the hypothalamic
      pituitary-gonadal axis in reproduction. The objective of the current study is to
      understand the molecular mechanisms underlying transcriptional regulation of SF-1
      gene expression in the pituitary. We have studied a series of deletion and point
      mutations in the SF-1 promoter region for transcriptional activity in alphaT3-1
      and L/betaT2 (pituitary gonadotrope), CV-1, JEG-3, and Y1 (adrenocortical) cell
      lines. Our results indicate that maximal expression of the SF-1 promoter in all
      cell types requires an E box element at -82/-77. This E box sequence (CACGTG) is
      identical to the binding element for USF (upstream stimulatory factor), a member
      of the helix-loop-helix family of transcription factors. Studies of the SF-1 gene
      E box element using gel mobility shift and antibody supershift assays indicate
      that USF may be a key transcriptional regulator of SF-1 gene expression.

PMID- 9605935
TI  - A novel thyroid transcription factor is essential for thyrotropin-induced up
      regulation of Na+/I- symporter gene expression.
AB  - The stimulation of iodide (I-) transport by TSH in FRTL-5 thyroid cells is partly
      due to an increase in Na+/I- symporter (NIS) gene expression. The identification
      of a TSH-responsive element (TRE) in the NIS promoter and its relationship to the
      action of thyroid transcription factor-1 (TTF-1) on the promoter are the subjects
      of this report. By transfecting NIS promoter-luciferase chimeric plasmids into
      FRTL-5 cells in the presence or absence of TSH, we identify a TRE between -420
      and -370 bp of the NIS 5'-flanking region. Nuclear extracts from FRTL-5 cells
      cultured in the absence of TSH form two groups of protein-DNA complexes, A and B,
      in gel mobility shift assays using an oligonucleotide having the sequence from 
      420 to -385 bp. Only the A complex is increased by exposure of FRTL-5 cells to
      TSH or forskolin. The addition of TSH to FRTL-5 cells can increase the A complex
      at 3-6 h, reaching a maximum at 12 h. FRTL-5, but not nonfunctioning FRT thyroid
      or Buffalo rat liver (BRL) cell nuclear extracts, form the A complex. The TSH
      increased nuclear factor in FRTL-5 cells interacting with the NIS TRE is distinct
      from TTF-1, thyroid transcription factor-2, or Pax-8, as evidenced by the absence
      of competition using oligonucleotides specific for these factors in gel shift
      assays. Neither is it the nuclear protein interacting with cAMP response element.
      The TRE is in the upstream of a TTF-1-binding site, -245 to -230 bp. Mutation of
      the TRE causing a loss of TSH responsiveness also decreases TTF-1-induced
      promoter activity in a transfection experiment. The formation of the A complex
      between FRTL-5 nuclear extracts and the NIS TRE is redox-regulated. In sum,
      TSH/cAMP-induced up-regulation of the NIS requires a novel thyroid transcription
      factor, which also appears to be involved in TTF-1-mediated thyroid-specific NIS
      gene expression.

PMID- 9605936
TI  - Signal transduction, desensitization, and recovery of responses to thyrotropin
      releasing hormone after inhibition of receptor internalization.
AB  - Three independent methods were used to block internalization of the TRH receptor:
      cells were infected with vaccinia virus encoding a dominant negative dynamin,
      incubated in hypertonic sucrose, or stably transfected with a receptor lacking
      the C-terminal tail. Internalization was blocked in all three paradigms as judged
      by microscopy using a fluorescently labeled TRH agonist and biochemically. The
      initial inositol trisphosphate (IP3) and Ca2+ responses to TRH were normal when
      internalization was inhibited. The IP3 increase was sustained rather than
      transient, however, in cells expressing the truncated TRH receptor, implying that
      the C-terminal tail of the receptor may be important for uncoupling from
      phospholipase C. After withdrawal of TRH, cells were refractory to TRH until both
      ligand dissociation and resensitization of the receptor had occurred. When
      surface-bound TRH was removed by a mild acid wash, which did not impair receptor
      function, neither wild-type nor truncated receptors were able to generate full
      IP3 responses for about 10 min. The rate of recovery was not altered by blocking
      internalization. Recovery of intracellular Ca2+ responses also depended on the
      rate of Ca2+ pool refilling. In summary, in the continued presence of TRH,
      phospholipase C activity declines quickly due to receptor uncoupling; this
      desensitization does not take place for the truncated receptor. After TRH is
      withdrawn, cells are refractory to TRH. Before cells can respond, TRH must
      dissociate and a resensitization step, which takes place on the plasma membrane
      and does not require the C-terminal tail of the receptor, must occur.

PMID- 9605938
TI  - The carboxyl-terminal region is a determinant for the intracellular behavior of
      the chorionic gonadotropin beta subunit: effects on the processing of the Asn
      linked oligosaccharides.
AB  - The placental hormone human CG (hCG) consists of two noncovalently linked alpha-
      and beta-subunits similar to the other glycoprotein hormones LH, FSH, and TSH.
      These heterodimers share a common alpha subunit but differ in their structurally
      distinct beta subunits. The CGbeta subunit is distinguished among the beta
      subunits by the presence of a C-terminal extension with four serine-linked
      oligosaccharides (carboxyl terminal peptide or CTP). In previous studies we
      observed that deleting this sequence decreased assembly of the truncated CGbeta
      subunit (CGbeta114) with the alpha-subunit and increased the heterogeneity of the
      secreted forms of the uncombined subunit synthesized in transfected Chinese
      hamster ovary (CHO) cells. The latter result was attributed to alterations in the
      processing of the two N-linked oligosaccharides. To examine at what step this
      heterogeneity occurs, the CGbeta and CGbeta114 genes were transfected into wild
      type and mutant CHO cell lines that are defective in the late steps of the N
      linked carbohydrate-processing pathway. We show here that removal of the CTP
      alters the processing of the core mannosyl unit of the subunit to complex forms
      at both glycosylation sites and that the oligosaccharides contain
      polylactosamine. Although it has been presumed that there is little
      intramolecular interaction between the CTP and the proximal domains of the
      subunit, our data suggest that the CTP sequence participates in the folding of
      the newly synthesized subunit, which is manifest by the posttranslational changes
      observed here.

PMID- 9605937
TI  - Identification of binding domains of the growth hormone-releasing hormone
      receptor by analysis of mutant and chimeric receptor proteins.
AB  - The hypothalamic peptide GH-releasing hormone (GHRH) stimulates the release of GH
      from the pituitary through binding and activation of the GHRH receptor, which
      belongs to the family of G protein-coupled receptors. The objective of this study
      was to identify regions of the receptor critical for interaction with the ligand
      by expressing and analyzing truncated and chimeric epitope-tagged GHRH receptors.
      Two truncated receptors, GHRHdeltaN, in which part of the N-terminal domain
      between the putative signal sequence and the first transmembrane domain was
      deleted, and GHRHdeltaC, which was truncated downstream of the first
      intracellular loop, were generated. Both the receptors were deficient in ligand
      binding, indicating that neither the N-terminal extracellular domain (N terminus)
      nor the membrane-spanning domains with the associated extracellular loops (C
      terminus) are alone sufficient for interaction with GHRH. In subsequent studies,
      chimeric proteins between the receptors for GHRH and vasoactive intestinal
      peptide (VIP) or secretin were generated, using the predicted start of the first
      transmembrane domain as the junction for the exchange of the N terminus between
      receptors. The chimeras having the N terminus of the GHRH receptor and the C
      terminus of either the VIP or secretin receptor (GNVC and GNSC) did not bind GHRH
      or activate adenylate cyclase after GHRH treatment. The reciprocal chimeras
      having the N terminus of either the VIP or secretin receptors and the C terminus
      of the GHRH receptor (VNGC and SNGC) bound GHRH and stimulated cAMP accumulation
      after GHRH treatment. These results suggest that although the N-terminal
      extracellular domain is essential for ligand binding, the transmembrane domains
      and associated extracellular loop regions of the GHRH receptor provide critical
      information necessary for specific interaction with GHRH.

PMID- 9605939
TI  - Effects of body position and liquid meal ingestion on esophageal acid exposure
      time in healthy subjects.
AB  - We investigated the effect of body position and ingestion of a test liquid meal
      on esophageal acid exposure time in 20 asymptomatic healthy subjects.
      Intraesophageal pH monitoring was performed for 1 h before meals and 3h
      postprandially with the subject in the supine (n = 10) or sitting position (n =
      10). The test meal had a total volume of 800 ml and an energy content of 500
      kcal. Esophageal acid exposure time was defined as the percentage of time at pH <
      4.0. There was no difference in preprandial or postprandial esophageal acid
      exposure time between the supine and sitting positions. Esophageal acid exposure
      time for the 3-h postprandial period was significantly greater than that for the
      preprandial period in both the supine and the sitting positions. The difference
      in body position did not influence preprandial or postprandial esophageal acid
      exposure time, but ingestion of the liquid meal significantly increased the
      esophageal acid exposure time in both the supine and sitting positions in
      asymptomatic healthy subjects.

PMID- 9605940
TI  - Role of extravariceal collateral channels in the development of portal
      hypertensive gastropathy before and after sclerotherapy.
AB  - We investigated whether extravariceal collateral pattern contributed to the
      development of portal-hypertensive gastropathy (PHG) before and after
      sclerotherapy. Ninety-nine patients with cirrhosis and large esophageal varices
      were examined in this retrospective study. They were divided into four groups
      according to transhepatic portographic findings: group A (with neither
      paraesophageal veins nor gastrorenal shunt; n = 46), group B (with paraesophageal
      veins; n = 27), group C (with gastrorenal shunt; n = 14), and group D (with
      paraesophageal veins and gastrorenal shunt; n = 12). To assess PHG, endoscopic
      examinations were carried out before and 1 week and 1 month after sclerotherapy.
      The severity of PHG was classified according to a modified McCormack's
      classification and scored as: absence, 0; mild, 1; severe, 2. There were no
      significant differences in age, sex, cause of cirrhosis, severity of liver
      dysfunction, and extent of esophageal varices in the four groups. The PHG score
      before sclerotherapy was significantly higher in group A than in either group C
      (P < 0.05) or group D patients (P < 0.05). The calculated, integrated incremental
      change in PHG score after sclerotherapy was significantly higher in group A than
      in group C (P < 0.01) and group D patients (P < 0.01). Although the integrated
      change in PHG score was lower in group B than in group A patients, the difference
      was not significant (P = 0.68). These results suggest that gastrorenal shunt, but
      not paraesophageal veins, may play a protective role in the development of PHG
      before and after sclerotherapy.

PMID- 9605941
TI  - Detection of genes of RNA viruses from freshly biopsied gastric mucosa by reverse
      transcription polymerase chain reaction.
AB  - The reverse transcription polymerase chain reaction (RT-PCR) was performed to
      detect genes of RNA viruses in the freshly biopsied gastric mucosa of seven
      patients with low gastric acidity. Although nucleoprotein genes of Sendai virus
      and hemmaglutinin genes of influenza virus A were not detected, nucleoprotein
      genes of influenza virus B were detected in samples from three of the seven
      patients. The first patient had had antrectomy and vagotomy for gastric ulcer,
      the second patient was receiving a histamine type 2 receptor blocker for
      gastritis, and the third patient was receiving a proton pump inhibitor for
      gastric ulcer. Virus isolation from gastric mucosa and from gargles was negative
      for all seven patients. These findings suggest that genes of influenza viruses
      may exist in the gastric mucosa of patients with low gastric acidity.

PMID- 9605942
TI  - Effects of teprenone on gastric epithelial restoration in a rabbit cultured cell
      model.
AB  - The mechanism of action of gastrocytoprotective agents is not fully understood.
      We assessed the effects of an anti-ulcer agent, teprenone, and bile acid on
      epithelial restoration. Teprenone with or without deoxycholic acid was added to a
      complete confluent cultured gastric epithelial cell sheet after wounding.
      Restoration was monitored for 48 h, and the wound size was assessed. Migration
      velocity was measured, and proliferation was detected by sequential staining with
      bromodeoxyuridine. The labeling index was calculated. Restoration was completed
      within 48h in controls, whereas deoxycholic acid retarded repair. The migration
      velocity was suppressed by deoxycholic acid treatment. The number of
      proliferative cells peaked at 36 h (labeling index, 1.7%) in controls. In the
      deoxycholic acid group, the maximal labeling index was 0.5% at 48 h. Teprenone
      abolished the bile acid-induced retardation. Teprenone showed cytoprotective
      effects against deoxycholic acid-induced inhibition of epithelial cell migration
      and proliferation.

PMID- 9605943
TI  - Relevance of antibiotic sensitivities in predicting failure of omeprazole,
      clarithromycin, and tinidazole to eradicate Helicobacter pylori.
AB  - Omeprazole 20 mg once (o.d.) or twice daily (b.d.), clarithromycin 250 mg b.d.,
      and tinidazole 500 mg b.d. for 7 days (OCT) is an effective regimen against
      Helicobacter pylori, but the effect of 5-nitroimidazole resistance is unclear. We
      aimed to evaluate this using the disc diffusion technique (Mast Diagnostics,
      Bootle, UK) and E-test (Cambridge Diagnostics Services, Cambridge, UK) to assess
      5-nitroimidazole resistance. H. pylori was cultured from antral biopsies of
      infected patients, as determined by 13C-urea breath test (13C-UBT), histology,
      and/or rapid urease test. Patients were prescribed OCT and H. pylori eradication
      was assessed by 13C-UBT at least 4 weeks after completion of therapy. Antibiotic
      sensitivities to metronidazole and clarithromycin were evaluated by the disc
      diffusion method and by the measurement of minimum inhibitory concentration (MIC)
      using the E-test. One hundred and forty-one H. pylori-infected patients were
      enrolled in the study and the organism was successfully cultured from 119
      patients (84%). The overall eradication rate was 125/141 (89%). OCT was
      successful in 62/69 (90%) patients harboring fully sensitive strains of H.
      pylori, compared with 42/45 (93%) of patients with strains that were resistant to
      metronidazole alone (P = 0.74, Fisher's exact test). MIC was assessed in 22
      samples. Using a cut-off point of >32 microg/ml to define metronidazole
      resistance eradication rates were higher against sensitive (9/12; 75%) than
      resistant (3/10; 30%) strains (P = 0.08, Fisher's exact test). 5-Nitroimidazole
      resistance assessed by the disc diffusion technique is not helpful in predicting
      OCT failure, but the E-test may be of value.

PMID- 9605944
TI  - Enhancement of reactivity of anti-MUC1 core protein antibody and killing activity
      of anti-MUC1 cytotoxic T cells by deglycosylation of target tissues or cells.
AB  - MUC1 mucin core protein contains an important tumor-associated peptide antigen
      that can induce cytotoxic T cells (CTLs) in vivo, although this antigen is
      generally masked by mucin-type glycans. To reveal the precise expression pattern
      of MUC1 protein in normal and neoplastic gastric tissues, we performed
      immunohistochemical staining of periodic acid-treated tissue sections with an
      anti-MUC1 core protein monoclonal antibody (mAb), MUSE11. In non-cancerous
      tissues, the deep portion of fundic glands and the luminal surface were
      predominantly immunostained in normal and metaplastic glands, respectively. In
      cancerous tissues, the incidence of positivity for MUC1 protein varied from 67%
      to 88%, depending on histological type. This frequent expression of MUC1 protein
      in cancer tissues after periodic acid treatment suggested that deglycosylation
      may be of use for exposing the target antigen of anti-MUC1 CTLs. Accordingly, we
      then examined the effect of benzyl-alpha-GalNAc, an inhibitor of O-glycan
      biosynthesis, on the expression of MUC1 protein and sensitivity to an anti-MUC1
      CTL line, designated TS, in gastric cancer JRST cells. After incubation with
      benzyl-alpha-GalNAc, the reactivity of mAb MUSE11 with JRST cells and their
      sensitivity of TS were clearly increased. These findings suggest that
      deglycosylation may offer an important strategy for enhancing anti-tumor immunity
      in patients with gastric cancer.

PMID- 9605945
TI  - Hepatocyte growth factor accelerates restitution of intestinal epithelial cells.
AB  - Many cytokines are involved in the repair of damaged tissue, and one of these,
      hepatocyte growth factor (HGF), is involved not only with liver regeneration but
      also in the repair of other tissues. To investigate the importance of HGF in the
      repair of the small intestine, we evaluated its effect and that of other growth
      factors in IEC-6 cells, an intestinal epithelial cell line derived from normal
      rat small intestine. Round "wounds" were made in confluent monolayers of IEC-6 by
      silicon rubber-tipped steel rods and various cytokines; transforming growth
      factor alpha (TGF-alpha), transforming growth factor beta1 (TGF-beta1),
      keratinocyte growth factor (KGF), and HGF, were added. We photographed the
      repaired monolayers every 24 h and calculated the ratios of areas not covered by
      cells to initial areas. Cell proliferation with TGF-alpha, TGF-beta, KGF, or HGF
      was examined in terms of [3H]-thymidine uptake. Finally, we determined c-met (the
      HGF receptor) mRNA in the IEC-6 cells by Northern blot hybridization. HGF was the
      most potent of the cytokines in accelerating repair of the damaged monolayer of
      IEC-6. HGF was also 1.34 times more effective than control the medium for
      inducing cell proliferation of IEC-6. By Northern blot hybridization, three bands
      of mRNA bound to c-met cDNA. These results suggest that HGF is important in the
      repair of the small intestine.

PMID- 9605946
TI  - Effects of germinated barley foodstuff on dextran sulfate sodium-induced colitis
      in rats.
AB  - Germinated barley foodstuff (GBF), derived from the aleurone and scutellum
      fractions of germinated barley, is rich in glutamine and low-lignified
      hemicellulose, and increases mucosal protein, RNA, and DNA content in the
      intestine when fed to normal rats. The aim of this study was to evaluate the
      effects of feeding GBF or germinated gramineous seeds on experimental ulcerative
      colitis. Sprague-Dawley rats that received 3% dextran sulfate sodium in their
      diets were used as an experimental colitis model. The effects of sulfasalazine, a
      drug used to treat inflammatory bowel disease, were compared with those of GBF.
      After rats had consumed diets containing GBF or various aleurone and scutellum
      fractions, mucosal damage; the content of mucosal protein, RNA, and DNA in the
      colo-rectum; and serum interleukin-8 and alpha1-acid glycoprotein levels were
      assessed. GBF and germinated seeds more effectively prevented bloody diarrhea and
      mucosal damage in colitis compared with controls and rats receiving
      sulfasalazine, but non-germinated samples did not have a protective effect. GBF
      increased mucosal protein and RNA content in the colitis model. The consumption
      of GBF appears to prevent inflammation in a colitis model, and its effect seems
      to be related to the germination process. GBF and germinated seeds have the
      potential to serve as nutritional therapy for ulcerative colitis.

PMID- 9605947
TI  - Infiltration of peroxidase-producing eosinophils into the lamina propria of
      patients with ulcerative colitis.
AB  - Little information is available to explain the pathogenesis of ulcerative colitis
      (UC). In this study, we focused on eosinophils in the lamina propria of the
      mucosa of patients with UC in the active phase. Biopsy specimens were taken from
      17 patients with UC in the active phase, 17 in the inactive phase, and 20 control
      patients, and submitted for histochemical staining for peroxidase and
      chloroacetate esterase for microscopic examination. Both peroxidase-producing and
      chloroacetate esterase-producing cells in the lamina propria increased markedly
      in the active phase (8.3 +/- 3.1/0.01 mm2 and 6.6 +/- 2.7/0.01 mm2,
      respectively), compared with values in the inactive phase (0.8 +/- 0.6/0.01 mm2
      and 1.3 +/- 0.6/0.01 mm2) or in the controls (1.3 +/- 0.8/0.01 mm2 and 1.3 +/-
      0.4/0.01 mm2). Triple staining for peroxidase, chloroacetate esterase, and
      nonspecific esterase in the specimens revealed that the peroxidase-producing
      cells constituted a different population from that of neutrophils,
      macrophages/monocytes, or basophils. A monoclonal antibody specific for
      eosinophil peroxidase stained almost all infiltrated peroxidase-producing cells.
      These results indicated that eosinophils with strong peroxidase activity had
      infiltrated the lamina propria in UC, suggesting an allergic background and the
      involvement of released peroxidase in the mucosal damage characteristic of UC.

PMID- 9605948
TI  - Steroid complications and surgery in intractable ulcerative colitis.
AB  - The major operative indication for ulcerative colitis is intractability. Although
      steroid side effects appear to be closely associated with surgical indications
      for intractable ulcerative colitis, this relationship has yet to be analyzed in
      detail. To elucidate this relationship, we investigated 39 surgical patients with
      intractable ulcerative colitis, as defined by the Research Committee for
      Intractable Diseases of the Ministry of Health and welfare of Japan, and 66
      conservatively treated patients with ulcerative colitis, of whom 6 had
      intractable disease. All patients with major steroid side effects and 17/24 (71%)
      patients with minor side effects underwent surgery. The median number of
      admissions was higher in patients with major side effects than in those with less
      severe or no side effects in the operative series, while this value was lower in
      the non-operative series than in the operative series. This tendency was similar
      for the total duration of hospitalization and the number of relapses. In the
      operative series, markedly higher steroid doses were administered to patients
      with side effects than to those without, and lower doses were given in the non
      operative series. On multivariate regression analysis, the presence of steroid
      side effects, disease extent, and disease duration were significantly associated
      with surgery. Patients without side effects had a higher postoperative
      complication rate than those with minor side effects. We conclude that major side
      effects are a surgical indication for patients with intractable ulcerative
      colitis, and that even minor side effects should be taken as a surgical
      indication in view of the patient's quality of life.

PMID- 9605949
TI  - Colorectal perforation with barium enema in the elderly: case analysis with the
      POSSUM scoring system.
AB  - Colorectal perforation is a serious complication of barium-enema examination, as
      the resultant contamination of the intraperitoneal or extraperitoneal space may
      result in a severe septic course. Between 1 October 1993 and 30 September 1996,
      four patients had colorectal injuries after barium-enema examinations at the Far
      Eastern Memorial Hospital, Taipei, Taiwan. Their mean age was 80 years and three
      of them died, despite the implementation of early and aggressive treatment. To
      examine the differences between this high crude mortality rate and reports of
      zero mortality, we retrospectively analyzed the data with the well established
      predictive surgical scoring system, the Physiological and Operative Severity
      Score for the enUmeration of Morbidity and mortality (POSSUM), to estimate the
      potential risk of death in these four patients.

PMID- 9605950
TI  - Inhibitory effects of n-3 polyunsaturated fatty acids on sigmoid colon cancer
      transformants.
AB  - Various types of polyunsaturated fatty acids (PUFAs) have been suggested to exert
      different effects on the colon in terms of promotion or inhibition of tumor
      development. Results of in vitro and in vivo studies are, however, inconsistent
      and it remains unclear whether or not the cellular effects of PUFAs change along
      with the malignant transformation of colonic cells. In this study, we used the
      NIH3T3 cell line and its SIC (sigmoid colon cancer) oncogene transformants to
      compare the effects of PUFAs on the proliferation of non-malignant and malignant
      cells. We also determined the cellular utilization of fatty acids in media by a
      high-performance liquid chromatography method. The addition of exogenous
      arachidonic acid (ARA, an n-6 fatty acid), eicosapentaenoic acid (EPA, n-3), and
      docosahexaenoic acid (DHA, n-3) exerted different effects on NIH3T3 cells, and on
      SIC transformants, in which selective inhibitory effects were observed at media
      concentrations ranging from 10 to 20 microg/ml. In cells cultured in media
      supplemented with EPA or DHA at a concentration of 2 microg/ml, which had no
      effect on cell proliferation, the cellular utilization of linoleic acid (n-6), a
      precursor of n-3 fatty acids, was inhibited. This inhibition was stronger in SIC
      transformants than in NIH3T3 cells (P < 0.05). There was no difference in the
      utilization of fatty acids between the two cell lines cultured in media
      supplemented with ARA. We conclude that the cellular response to exogenous long
      chain PUFAs is modified during the course of malignant transformation, and that
      EPA and DHA (n-3 PUFAs) appear to have specific inhibitory effects on cancer
      cells and may thus enhance the host defense against colon cancer.

PMID- 9605951
TI  - Increased mRNA expression of a novel prostacyclin-stimulating factor in human
      colon cancer.
AB  - We recently cloned a prostacyclin (PGl2)-stimulating factor (PSF), which
      stimulates PGl2 production by cultured vascular endothelial cells.
      Immunohistochemistry and Northern blot analysis demonstrated that PSF was highly
      expressed in colon cancer sites compared with normal colon mucosa obtained from
      the same patient, as well as in cultured adenocarcinoma cell lines compared with
      cultured normal colon mucosal cell lines. Increased levels of the PSF protein
      were detected in the culture media of these adenocarcinoma cells compared with
      levels in the culture media of normal mucosal cells. These results suggest that
      PSF is closely associated with carcinogenesis of colon mucosa.

PMID- 9605952
TI  - Sero-epidemiologic study of hepatitis C virus infection in Fukuoka, Japan.
AB  - We conducted an epidemiological study of 509 residents of H town, Fukuoka, Japan,
      to investigate the high mortality rate from liver disease. Antibodies to
      hepatitis C virus (HCV) (anti-HCV) were detected in 120 residents (23.6%); HCV
      RNA in 91 (17.9%), and hepatitis B surface antigen (HBsAg) in 13 (2.6%).
      Multivariate logistic regression analyses showed that presence of anti-HCV, male
      gender, and history of liver disease were associated with the presence of liver
      dysfunction, and that age of more than 40 years and a particular district were
      associated with the presence of anti-HCV. HCV RNA was more frequently detected in
      anti-HCV-positive men than women (41, or 85.4% versus 50, or 69.4%) (P < 0.05).
      The incidence of liver dysfunction was significantly higher in HCV RNA-positive
      men than women (32, or 66.7% versus 22, or 30.6%) (P < 0.05). These findings
      suggest that: (1) HCV was correlated with the high mortality rate from liver
      diseases, (2) there were district-related differences in the incidence of HCV,
      and (3) the lower frequency of elimination of HCV from men may explain why they
      showed a high mortality from liver disease.

PMID- 9605953
TI  - Usefulness of hepatitis C virus RNA counts by second generation HCV bDNA-probe in
      chronic hepatitis C based on the HCV genotype.
AB  - Detection of hepatitis C virus (HCV) RNA by a second generation (ver 2) HCV bDNA
      probe method (bDNA-probe) was compared with detection by the first generation
      (ver 1) assay. The two assays were performed simultaneously with the same serum
      samples of HCV genotypes 1b, 2a, 2b, 3a, and 3b. The positive rates with ver 1
      were 82% for HCV genotype 1b (type 1b), 57.6% for HCV genotype 2a (type 2a),
      75.0% for HCV genotype 2b (type 2b), 55.6% for HCV genotype 3a (type 3a), and
      93.8% for HCV genotype 3b (type 3b). The positive rates with ver 2 were 95.0% for
      type 1b, 93.9% for type 2a, 83.3% for type 2b, 100% for type 3a, and 93.8% for
      type 3b. With Fisher's exact test, the detection rate for type 2a was
      significantly higher (P = 0.001) with ver 2 than with ver 1. We obtained
      regression lines using the HCV counts measured by bDNA-probe on the y axis and
      the HCV counts obtained by an HCV reverse transcriptase (RT)-competitive
      polymerase chain reaction method (competitive PCR) on the x axis. The gradients
      for types 1b, 2a, and 3b were greater with ver 2 compared to ver 1. The gradients
      for types 2a and 3b were the highest: for type 2a, y = 0.135x + 0.6 with ver 1
      and y = 0.248x + 0.1 with ver 2; for type 3b, y = 0.366x + 0.1 with ver 1 and y =
      0.727x + 0.3 for ver 2. In addition, HCV-RNA counts for all the genotypes tested
      in this study were significantly higher with ver 2 than with ver 1. Hence, we
      conclude that ver 2 of the bDNA-probe measures HCV-RNA counts closer to those
      obtained with competitive PCR than the ver 1 assay.

PMID- 9605954
TI  - Multiple regression analysis for assessing the growth of small hepatocellular
      carcinoma: the MIB-1 labeling index is the most effective parameter.
AB  - The aim of this study was to clarify whether histological parameters reflected
      tumor aggressiveness in patients with hepatocellular carcinoma (HCC). The tumor
      volume doubling times (TVDTs) of 21 HCCs, less than 3 cm in diameter at the start
      of the observation period, were calculated in 21 patients in whom the natural
      progression of the lesion was observed by ultrasonography. Paraffin-embedded
      sections were prepared from samples obtained by ultrasound-guided fine-needle
      liver biopsy at the end of the observation period. The histological parameters
      examined were the MIB-1 labeling index (LI), for which we performed
      immunohistochemical staining with the MIB-1 monoclonal antibody, using an antigen
      retrieval method; the nucleo-cytoplasmic (N/C ratio), cellularity, and the
      nuclear form factor (NFF), were calculated with an imaging analyzer. We performed
      multiple regression analysis for estimating the growth of small HCCs. With the
      N/C ratio (0.154 +/- 0.068; mean +/- SD), cellularity (453 +/- 21.8 cells/10(4)
      microm2), NFF (1.150 +/- 0.096), and degree of HCC differentiation as independent
      variables, only the MIB-1 LI (11.8 +/- 6.1%) showed a significant correlation
      with TVDT (207.5 +/- 162.6 days) (r = -0.658; P < 0.05). Compared to the
      conventional indices of histological atypism tested, i.e., N/C ratio, cellularity
      NFF, and degree of HCC differentiation, only MIB-1 LI was significantly
      correlated with small HCC growth rate. The MIB-1 LI may therefore be a simple and
      useful index of tumor aggressiveness.

PMID- 9605955
TI  - Longitudinal changes of bone mineral content with age in patients with cirrhosis
      of the liver.
AB  - Bone disorders are associated with cirrhosis. Knowledge of the natural course of
      bone changes in cirrhosis could help in decision-making about medical treatment.
      We carried out one measurement of bone mineral density (BMD) in 184 Japanese
      patients (98 men and 86 women) with cirrhosis by dual-energy X-ray
      absorptiometry. Differences in BMD values means +/- SD between the 98 cirrhotic
      men and 283 healthy men of the same age reported in another study were not
      significant. In the 86 cirrhotic women, BMD tended to show a greater decrease
      with age than in healthy controls reported elsewhere. Differences in BMD values
      (means +/- SD) between 622 healthy women reported elsewhere and our patients were
      not significant for women up to age 60 years, but at 60 years or more, the mean
      BMD in cirrhotic women (0.692 +/- 0.100) was lower than that in healthy women
      (0.749 +/- 0.101; P < 0.01). In 61 of the 184 patients (31 men and 30 women), the
      bone mineral content (BMC) of lumbar vertebrae was measured at least twice, at
      intervals of 10-72 months. In this longitudinal part of the study, the group mean
      of estimated annual change for cirrhotic men was -0.4%, close to that of healthy
      men (-0.2%). This mean in cirrhotic women was -2.8%, significantly different from
      that of healthy women (-1.1%; P < 0.05). As expected, cirrhotic women were the
      most likely to lose BMC, and many needed prompt treatment.

PMID- 9605956
TI  - Long-term prognosis of non-shunt operation for idiopathic portal hypertension.
AB  - This report presents 46 Japanese patients with idiopathic portal hypertension
      (IPH) in whom non-shunt operation was performed for the management of esophageal
      varices. Non-shunt operation included transthoracic esophageal transection
      (Sugiura's procedure) in 37 patients, transabdominal esophageal transection
      (TAET) in 3 patients, and Hassab's procedure in 6 patients. Rates of
      postoperative variceal eradication were: 78.4% by Sugiura's procedure; 100% by
      TAET; and 50% by Hassab's procedure. The cumulative rates for recurrent varices
      and recurrent bleeding were 3.9%, and 5.1%, respectively, at 5 years, and 8.9%
      and 9.8% at both 10 and 15 years. Only 3 patients required additional endoscopic
      injection sclerotherapy to treat recurrent varices. Although 3 patients developed
      upper gastrointestinal bleeding, the source of hemorrhage was esophageal varices
      in 1, and portal hypertensive gastropathy in 2; none of the patients died from
      bleeding. Actuarial survival for all patients was 87.5% at 5 years, 77.9% at 10
      years, and 58.8% at 15 years. There were no deaths within the first 30 days after
      surgery. These results show that non-shunt operation is useful in preventing
      bleeding from esophageal varices in patients with IPH.

PMID- 9605957
TI  - Reduced reactivity of pancreatic exocrine secretion in response to
      gastrointestinal hormone in WBN/Kob rats.
AB  - We compared pancreatic exocrine secretion in 5-month-old WBN/Kob rats, a model of
      chronic pancreatitis, with that in Wistar rats of the same age in a conscious
      state. Basal pancreatic secretion and pancreatic wet weight in WBN/Kob rats were
      lower than the values for Wistar rats. There was no difference in plasma
      cholecystokinin (CCK) concentration between the two types of rats. When CCK-8 was
      intravenously administered, the stimulation of pancreatic protein secretion in
      WBN/Kob rats was weaker than that in Wistar rats. When bile and pancreatic juice
      were diverted from the duodenum, the resulting increase in the plasma CCK
      concentration was similar in both types of rats, but stimulation of the volume
      and protein output of pancreatic juice in WBN/Kob rats was weaker than that in
      Wistar rats. In addition, WBN/Kob rats exhibited little increase in pancreatic
      wet weight because of this diversion. When secretin was intravenously
      administered, the stimulation of fluid secretion in WBN/ Kob rats was also weaker
      than that in Wistar rats. The binding of CCK-8 to pancreatic membrane fractions
      in WBN/Kob rats was much weaker than that in Wistar rats. Histological findings
      in WBN/Kob rat pancreas showed proliferation of fibrous tissue and atrophy of
      acinar cells. In conclusion, pancreatic exocrine secretion in response to the
      gastrointestinal hormones, CCK and secretin, was lower in WBN/Kob rats than in
      Wistar rats. These findings suggest that the hyposecretion of pancreas in WBN/Kob
      rats is hyporeaction of pancreatic membrane to gastrointestinal hormones.

PMID- 9605958
TI  - Clinical assessment of pancreatic diabetes caused by chronic pancreatitis.
AB  - Despite the high prevalence of diabetes mellitus in patients with chronic
      pancreatitis, few studies of pancreatic diabetes have been reported. We
      investigated 154 patients with chronic pancreatitis, of whom 50% were diabetics,
      with special reference to the features and clinical course of pancreatic
      diabetes. We arrived to clarify the features of pancreatic diabetes by comparing
      pancreatic exocrine function in 112 patients with primary diabetes with findings
      in a separate group of 80 patients with chronic pancreatitis. Pancreatic diabetes
      is proposed as a type of diabetes in which exocrine pancreatic function is
      markedly decreased. Progressive and fatal angiopathies were found in patients
      with pancreatic diabetes after a long duration of diabetes. The present
      investigation suggests that treatment of malnutrition is necessary in patients
      with pancreatic diabetes and that control of blood glucose is often difficult in
      these patients because of the high incidence of insulin-induced hypoglycemic
      episodes.

PMID- 9605959
TI  - Duodenal secretion of phospholipase A2, amylase, and bicarbonate in chronic
      pancreatitis.
AB  - Phospholipase A2 has been suggested to be involved in the pathogenesis and
      pathophysiology of acute pancreatitis. We determined phospholipase A2 and amylase
      activities in duodenal juice collected during a secretin test from 30 consecutive
      patients who were suspected to have chronic pancreatitis or biliary disease. The
      patients underwent endoscopic retrograde cholangiopancreatography (ERCP) the
      following day. In the 8 patients with ERCP findings of advanced chronic
      pancreatitis, the mean outputs of phospholipase A2, amylase, and bicarbonate were
      reduced by 74%, 72%, and 60% compared to the respective values in the 13
      (control) patients without a diagnosis of any pancreatic disorder or jaundice. In
      the 3 patients with recurrent pancreatitis but normal ERCP findings and in the 6
      patients with jaundice the output values were not significantly reduced compared
      to those in the patients without any pancreatic disorder or jaundice. The outputs
      of amylase and phospholipase A2 were not significantly interrelated, whereas the
      outputs of phospholipase A2 and bicarbonate correlated well. Receiver
      characteristic (ROC) curves confirmed the high specificity and sensitivity of
      phospholipase A2 or bicarbonate output in patients with ERCP findings of advanced
      chronic pancreatitis compared to those with no changes in pancreatic ducts, with
      similar probability values of 0.880 +/- 0.111 (SEM), compared to the respective
      lower value of amylase, 0.676 +/- 0.118. Phospholipase A2 and bicarbonate output
      proved of equal value as markers of chronic pancreatitis and were superior to
      amylase output in the secretin test.

PMID- 9605960
TI  - Gastrojejunal fistula caused by gastric ulcer.
AB  - We report a case of gastrojejunal fistula caused by benign gastric ulcer, a very
      rare condition. The patient was an 81-year-old-woman who had had multiple
      recurrences of gastric ulcer. She also had diabetes mellitus. She was admitted to
      our hospital because of a left femoral head fracture, necessitating a mechanical
      bone head exchange operation. She had severe abdominal pain and anemia on the
      48th postoperative day. Gastroendoscopic examination revealed a giant ulcer with
      a long-axis diameter of more than 5cm on the lesser curvature of the gastric
      body. She was treated with intravenous famotidine and all oral intake was
      restricted; her symptoms were alleviated. Two weeks later, a fistula had formed
      between the stomach and the jejunum just anal to the duodeno-jejunal flexure. She
      was placed on an ulcer diet, and was discharged with no symptoms on the 151st
      postoperative day. She has remained asymptomatic for 1 1/2, years to date. Lack
      of H2-antagonist administration, operative stress, and administration of
      ipriflavone appeared to have induced gastric ulcer recurrence, and formation of
      the fistula between the stomach and the jejunum seemed to have been facilitated
      by the patient being very lean and having minimal mesenteric adipose tissue.

PMID- 9605961
TI  - Ileo-abdominal wall fistula caused by diverticulum of the ileum.
AB  - We report a very rare case of ileo-abdominal fistula caused by penetration of the
      ileal diverticulum. Small bowel diverticulosis is generally considered to be an
      innocuous condition. In this report, we describe a case of ileal diverticulitis
      associated with an abdominal wall abscess.

PMID- 9605962
TI  - Carcinosarcoma of the colon: report of a case and review of the literature.
AB  - We report a case of carcinosarcoma in the transverse colon in a 60-year-old
      woman. She was admitted to our hospital for further examination of occult blood
      in October, 1995. Colonoscopy disclosed an elevated lesion with ulceration in the
      transverse colon, and she underwent right hemicolectomy. Histopathological
      examination revealed the tumor to consist of both carcinomatous and sarcomatous
      elements, the latter being more predominant. Immunohistochemistry revealed
      vimentin immunoreactivity in most of the sarcomatous cells, and S-100 and
      myoglobin in a few carcinomatous cells. Distinct carcinomatous features were
      noted in one superficial portion of the tumor, and these carcinomatous cells
      showed immunoreactivity for epithelial membrane antigen. The patient is alive 14
      months after surgery without evidence of recurrence. To our knowledge, this is
      the fourth reported case of carcinosarcoma of the colon. Our review of the
      literature disclosed poor prognosis in colonic carcinosarcoma.

PMID- 9605963
TI  - Aggressive jejunal gamma deltaT-cell lymphoma derived from intraepithelial
      lymphocytes: an autopsy case report.
AB  - A 69-year-old man with massive ascites was referred to our hospital. Paracentesis
      revealed exudative ascites with many abnormal lymphocytes, which expressed T
      natural killer (T-NK) cell surface markers and gamma deltaT-cell receptor (TCR).
      Although the ascites resolved for a short time with chemotherapy,
      gastrointestinal bleeding occurred and acute retention of ascites was observed.
      The patient died of panperitonitis. At autopsy, part of the jejunum revealed
      ulceration and marked mucosal thickening, and was perforated at the site of the
      severe ulceration. Histological examination showed massive infiltration of
      abnormal lymphocytes that were positive for CD45RO. Therefore, the cells
      responsible for the jejunal lymphoma and ascites were thought to be derived from
      gamma deltaIEL.

PMID- 9605964
TI  - Macronodular multi-organs tuberculoma: CT and MR appearances.
AB  - The case of a 21-year-old woman presenting with macronodular multi-organs
      tuberculoma is reported. She was examined for pulmonary tuberculosis on a chest X
      ray film in January, 1995, and admitted with a cough, anorexia, and abdominal
      pain in July, 1996. Computed tomography revealed multiple calcified nodules with
      peripheral hypodense areas in the brain, and calcified hypodense masses in the
      liver and spleen. Magnetic resonance (MR) imaging showed hypointense masses in
      the liver and spleen on T1-weighted spin echo images and a hypointense mass with
      a hyperintense area on T2-weighted spin echo images. On contrast-enhanced dynamic
      MR images, the liver and spleen masses were unenhanced and hypointense with
      slight rim enhancement. T2-weighted spin echo images showed a round hypointense
      nodule in the right kidney and hydronephrosis and enlargement in the left kidney.
      Antituberculous treatment was started with a gradual improvement in her signs and
      symptoms. Her temperature became normal. However, she was systemically treated
      with antituberculous chemotherapy 10 months later, her condition worsened again.
      She died from increased intracranial pressure in August, 1997.

PMID- 9605965
TI  - Segmental groove pancreatitis accompanied by protein plugs in Santorini's duct.
AB  - "Groove pancreatitis", a form of segmental pancreatitis affecting the head of the
      pancreas, is localized within the "groove" between pancreas head, duodenum, and
      common bile duct. Differentiation between groove pancreatitis and pancreatic head
      carcinoma is often difficult. We report a case of groove pancreatitis in which a
      hypoechoic mass between the duodenal wall and pancreas was clearly imaged, and
      narrowing of the second portion of the duodenum and bile duct stenosis were also
      found. The diagnosis was confirmed by surgery (pylorus-preserving pancreato
      duodenectomy). The patient was relieved from abdominal pain post operation. Up to
      the present, the patient has been good condition. We review the clinicopathologic
      and radiologic features of groove pancreatitis in the Japanese literature and
      discuss the possible role of Santorini's duct in its pathogenesis. We consider
      that impacted protein plugs in Santorini's duct are a pathogenic factor in the
      development of groove pancreatitis. Therefore, the findings of Santorini's duct
      on endoscopic retrograde pancreatography are very important in the diagnosis of
      groove pancreatitis. Groove pancreatitis presents various clinical features, such
      as biliary stenosis, duodenal stenosis, and pancreatic mass, and often
      masquerades as pancreatic head carcinoma. This condition should be kept in mind
      in the differential diagnosis of pancreatic head carcinoma.

PMID- 9605966
TI  - Hepatic fibrosis as wound repair: a progress report.
AB  - The injury response of the liver fits within the general paradigm of wound
      repair. The overall repair response requires close coordination of several cell
      types and synthetic processes and is orchestrated by an interacting group of
      cytokines, extracellular matrix (ECM) proteins, and products of metabolism such
      as oxygen radicals. Many cytokines act over short distances, engaging specific
      receptors on their parent cell (autocrine) or on immediately adjacent cells
      (paracrine). The most prominent of these is transforming growth factor-beta
      (TGFbeta). The ECM also mediates cellular crosstalk and does so in two ways.
      Firstly, as a binder of cytokines, it is capable of concentrating, presenting, or
      sequestering these factors at specific locations. Secondly, like cytokines,
      individual ECM proteins interact with cells via specific receptors, many of which
      belong to the integrin family. Engagement of a receptor leads to its activation,
      followed by intracellular signaling events and modification of cell behavior.
      Recent work has identified a specific integrin on stellate cells (alpha1beta1) as
      critical to the contractility of these cells. Finally, contrary to the view once
      held of ECM as relatively inert "ground substance", this extracellular complex is
      highly dynamic, its cytokine- and cell-binding activities being subject to rapid
      change. Therefore, matrix proteinases also are important, both during the
      initiation of fibrosis in association with stellate cell activation, and during
      the resolution of the injury. As current research reveals the key elements of
      this regulatory network, new therapeutic modalities are emerging. The goal of
      therapy is to modify the extent of the repair response without deleting it.
      Strategies directed at several levels of regulation are under consideration,
      including agents that block cytokine effects (e.g., TGFbeta receptor antagonists)
      and direct inhibitors of stellate cell activation or contraction.

PMID- 9605967
TI  - Microtubule dynamics in serum-starved and serum-stimulated Swiss 3T3 mouse
      fibroblasts: implications for the relationship between serum-induced
      contractility and microtubules.
AB  - It has been established that cell contractility can be stimulated with low or
      depolymerizing doses of microtubule (MT) poisons. In addition, low doses of
      nocodazole and vinblastine have recently been shown to decrease MT dynamics in
      vivo. In this study, investigated whether there is a direct, or reciprocal
      feedback-type relationship between contractility and microtubule dynamics, by
      examining MT dynamic behavior in live cells under conditions where contractility
      is known to be altered. Quiescent, serum-starved Swiss 3T3 mouse fibroblasts have
      been shown to be weakened in their contractility; serum stimulation increases
      cell contractility and causes the formation of stress fibers and adhesion
      plaques. Growing (control), quiescent (Go), and serum-stimulated cells were
      injected with rhodamine-tubulin, and MT dynamics were determined by analysis of
      MT length changes obtained from digitized images of the extreme periphery of the
      cells, where the MT ends were readily apparent. The MTs in quiescent cells were
      less dynamic than those in control cells: the growth and shortening rates were
      reduced by 30% and 45%, respectively. Dynamicity decreased by 47%, and the MTs
      spent more time in pause. After serum stimulation, MT growth rate, dynamicity,
      and time spent in pause returned to control cell levels. Although the shortening
      rate increased by 28%, it remained significantly lower than in control cells. In
      this system, the serum-induced increase in contractility was accompanied by an
      increase in MT dynamics. However, increased contractility stimulated with low
      doses of MT poisons is known to be accompanied by a decrease in MT dynamics.
      These results suggest that the relationship between MT dynamics and contractility
      is an indirect one.

PMID- 9605968
TI  - Effect of precise mechanical loading on fibroblast populated collagen lattices:
      morphological changes.
AB  - The contraction of a collagen lattice by resident fibroblasts causes strains to
      be developed within that lattice. These strains can be increased or decreased by
      altering the aspect ratio (ratio of length/width/thickness) of the fibroblast
      populated collagen lattice, as the cross-sectional area resisting the strain is
      changed and by the application of an external load. The fibroblasts align
      themselves with the direction of the maximum principle strain; in effect, these
      cells are "hiding" from the perceived strain. The direction of the maximum
      principle strain can be predetermined by the use of a computational finite
      element analysis. Using the tensioning-Culture Force Monitor to apply pre
      determined loading patterns of known repeatable magnitudes, as calculated by the
      finite element analysis, we have succeeded in aligning fibroblasts into a
      deliberate predicted orientation. This study has shown that the resident
      fibroblast population will respond to changes in strain resulting from the most
      subtle of mechanical loads. This may be an important mechanism in development and
      repair of connective tissue.

PMID- 9605969
TI  - Early stages of spindle formation and independence of chromosome and microtubule
      cycles in Haemanthus endosperm.
AB  - We analyzed transformation of the interphase microtubular cytoskeleton into the
      prophase spindle and followed the pattern of spindle axis determination.
      Microtubules in endosperm of the higher plant Haemanthus (Scadoxus) were stained
      by the immunogold and immunogold silver-enhanced methods. Basic structural units
      involved in spindle morphogenesis were "microtubule converging centers." We
      emphasized the importance of relative independence of chromosomal and
      microtubular cycles, and the influence of these cycles on the progress of
      mitosis. Cells with moderately desynchronized cycles were functional, but extreme
      desynchronization led to aberrant mitosis. There were three distinct phases of
      spindle development. The first one comprised interphase and early to mid
      prophase. During this phase, the interphase microtubule meshwork radiating from
      the nuclear surface into the cytoplasm rearranged and formed a dense microtubule
      cage around the nucleus. The second phase comprised mid to late prophase, and
      resulted in the formation of normal (bipolar) or transitory aberrant (apolar or
      multipolar) prophase spindles. The third phase comprised late prophase with
      prometaphase. The onset of prometaphase was accompanied by a rapid association of
      microtubule converging centers with kinetochores. In this stage aberrant spindles
      transformed invariably into bipolar ones. Lateral association of a few bipolar
      kinetochore fibers at early prometaphase established the core of the bipolar
      spindle and its alignment. We concluded that (1) spindle formation is a largely
      independent microtubular process modified by the chromosomal/kinetochore cycle;
      and (2) the initial polarity of the spindle is established by microtubule
      converging centers, which are a functional substitute of the centrosome/MTOC. We
      believe that the dynamics of microtubule converging centers is an expression of
      microtubule self-organization driven by motor proteins as proposed by Mitchison
      [1992: Philos. Trans. R. Soc. Lond. B. 336:99].

PMID- 9605970
TI  - Relationship between moire patterns, tubulin shape, and microtubule polarity.
AB  - The polarity of microtubules is reflected in cryo-electron microscope images and
      in three-dimensional reconstructions [Chretien et al., 1996: Structure 4:1031
      1040; Sosa and Milligan, 1996: J. Mol. Biol. 260:743-755]. This paper shows how
      the directionality of the moire patterns and the shape of the tubulin subunits
      are related. Microtubules observed by cryo-electron microscopy show an arrowhead
      moire pattern that points toward the plus end of microtubules with a right-handed
      protofilament skew and toward the minus end of microtubules with a left-handed
      protofilament skew. On the other hand, three-dimensional reconstructions of
      microtubules observed from the plus end reveal a radial counterclockwise slew of
      the tubulin subunits. We show how these polar features are related and present
      unambiguous rules for determining the polarity on longitudinal and axial views of
      microtubules.

PMID- 9605971
TI  - Neurofilament subunits can undergo axonal transport without incorporation into
      Triton-insoluble structures.
AB  - We examined the form(s) in which NF subunits undergo axonal transport. Pulse
      chase radiolabeling analyses with 35S-methioinine revealed that newly synthesized
      Triton-soluble NF subunits accumulated within axonal neurites elaborated by
      NB2a/d1 neuroblastoma prior to the accumulation of Triton-insoluble subunits. Gel
      chromatographic, immunological, ultrastructural, and autoradiographic analyses of
      Triton-soluble axonal fractions demonstrated that radiolabeled, Triton-soluble
      subunits were associated with NFs. Triton-soluble, radiolabeled axonal NF
      subunits were also detected within retinal ganglion cell axons following
      intravitreal injection of 35S-methioinine. Microinjected biotinylated subunits
      were prominent within axonal neurites of NB2a/d1 cells and cultured dorsal root
      ganglion neurons substantially before they were retained following Triton
      extraction. Prevention of biotinylated subunit, but not dextran tracer,
      translocation into neurites by nocodazole confirmed that microinjected subunits
      did not enter axons merely due to diffusion or injection-based pressure. Immuno
      EM confirmed the association of biotin label with axonal NFs. These findings
      point towards multiple populations of NF subunits within axons and leave open the
      possibility that axonal NFs may be more dynamic than previously considered.

PMID- 9605972
TI  - Sites of monomeric actin incorporation in living PtK2 and REF-52 cells.
AB  - The purpose of this study was to analyze where monomeric actin first becomes
      incorporated into the sarcomeric units of the stress fibers. We microinjected
      fluorescently labeled actin monomers into two cell lines that differ in the
      sarcomeric spacings of alpha-actinin and nonmuscle myosin II along their stress
      fibers: REF-52, a fibroblast cell line, and PtK2, an epithelial cell line. The
      cells were fixed at selected times after microinjection (30 s and longer) and
      then stained with an alpha-actinin antibody. Localization of the labeled actin
      and alpha-actinin antibody were recorded with low level light cameras. In both
      cell types, the initial sites of incorporation were in focal contacts,
      lamellipodia and in punctate regions of the stress fibers that corresponded to
      the alpha-actinin rich dense bodies. The adherent junctions between the
      epithelial PtK2 cells were also initial sites of incorporation. At longer times
      of incorporation, the actin fluorescence extended along the stress fibers and
      became almost uniform. We saw no difference in the pattern of incorporation in
      peripheral and perinuclear regions of the stress fibers. We propose that rapid
      incorporation of monomeric actin occurs at the cellular sites where the barbed
      ends of actin filaments are concentrated: at the edges of lamellipodia, the
      adherens junctions, the attachment plaques and in the dense bodies that mark out
      the sarcomeric subunits of the stress fibers.

PMID- 9605973
TI  - FtsZ from Escherichia coli, Azotobacter vinelandii, and Thermotoga maritima-
      quantitation, GTP hydrolysis, and assembly.
AB  - We have cloned the ftsZ genes from Thermotoga maritima and Azotobacter vinelandii
      and expressed the proteins (TmFtsZ and AzFtsZ) in Escherichia coli. We compared
      these proteins to E. coli FtsZ (EcFtsZ), and found that several remarkable
      features of their GTPase activities were similar for all three species, implying
      that these characteristics may be universal among FtsZs. Using a calibrated
      protein assay, we found that all three FtsZs bound 1 mole guanine nucleotide per
      mole FtsZ and hydrolyzed GTP at high rates (> 2 GTP per FtsZ per min). All three
      required magnesium and a monovalent cation for GTP hydrolysis. Previous reports
      showed that EcFtsZ (and some other species) required potassium. We confirmed this
      specificity for EcFtsZ but found that potassium and sodium both worked for Az-
      and TmFtsZ. Specific GTPase activity had a striking dependence on FtsZ
      concentration: activity (per FtsZ molecule) was absent or low below 50 microg/ml,
      rose steeply from 50 to 300 microg/ml and plateaued at a constant high value
      above 300 microg/ml. This finding suggests that the active state requires a
      polymer that is assembled cooperatively at 50-300 microg/ml. A good candidate for
      the active polymer was visualized by negative stain electron microscopy--straight
      protofilaments and protofilament pairs were seen under all conditions with active
      GTPase. We suggest that the GTP hydrolysis of FtsZ may be coupled to assembly, as
      it is for tubulin, with hydrolysis occurring shortly after an FtsZ monomer
      associates onto a protofilament end. As a part of this study, we determined the
      concentration of EcFtsZ and TmFtsZ by quantitative amino acid analysis and used
      this to standardize the bicinchonic acid colorimetric assay. This is the first
      accurate determination of FtsZ concentration. Using this standard and
      quantitative Western blotting, we determined that the average E. coli cell has
      15,000 molecules of FtsZ, at a concentration of 400 microg/ml. This is just above
      the plateau for full GTPase activity in vitro.

PMID- 9605974
TI  - Plakoglobin induces desmosome formation and epidermoid phenotype in N-cadherin
      expressing squamous carcinoma cells deficient in plakoglobin and E-cadherin.
AB  - Pg is a homologue of beta-catenin and Armadillo, the product of the Drosophila
      segment polarity gene and has been shown to have both adhesive and signaling
      functions. It interacts with both classic and desmosomal cadherins. Pg
      interaction with the desmosomal cadherins is essential for desmosome assembly.
      Its precise role in the classic cadherin complexes is unclear, although Pg-E
      cadherin interaction appears to be necessary for the formation of desmosomes. In
      addition to cadherins in adhesion complexes, Pg interacts with a number of
      proteins involved in regulation of cell differentiation and proliferation such as
      Lef-1/Tcf-1 transcription factors and the tumor suppressor protein APC. In this
      study, we have introduced Pg cDNA into SCC9 cells, a Pg- and E-cadherin-deficient
      squamous cell carcinoma line, which also lacks desmosomes. These cells have both
      alpha-catenin and beta-catenin, display unusual expression of N-cadherin, and
      have the typical fibroblastic phenotype of transformed cells. Pg-expressing SCC9
      cells (SCC9P) formed desmosomes. Desmosome formation coincided with the
      appearance of an epidermoid phenotype, with increased adhesiveness and a contact
      dependent decrease in growth. Biochemical characterization of SCC9P cells showed
      an increase in the expression and stability of N-cadherin and a decrease in level
      and stability of beta-catenin, without any apparent effects on alpha-catenin.
      These results show that, in the absence of E-cadherin, Pg can efficiently use N
      cadherin to induce desmosome formation and epidermoid phenotype. They also
      suggest a role for Pg as one of the regulators of the intracellular beta-catenin
      levels and underscore the pivotal role of this protein in regulating cell
      adhesion and differentiation.

PMID- 9605975
TI  - Immunophenotyping of bronchoalveolar lavage lymphocytes.

PMID- 9605976
TI  - Poliomyelitis: present epidemiological situation and vaccination problems.

PMID- 9605977
TI  - Interleukin-1beta expression after inhibition of protein phosphatases in
      endotoxin-tolerant cells.
AB  - Endotoxin (lipopolysaccharide [LPS]) is a potent activator of a number of
      inflammatory genes in blood leukocytes, including interleukin-1 (IL-1). Blood
      leukocytes isolated from patients with septic shock fail to produce IL-1 in
      response to LPS, a phenomenon known as endotoxin tolerance. To study the
      regulation of IL-1 expression in endotoxin-tolerant cells, the protein
      phosphatase inhibitor okadaic acid was used to examine the effects of protein
      phosphorylation on IL-1beta gene expression. We found that endotoxin-tolerant
      cells produced normal levels of IL-1beta when protein phosphatases were
      inhibited. In the human pro-monocytic cell line THP-1, okadaic acid increased
      mRNA accumulation and synthesis of IL-1beta protein. Normal and endotoxin
      tolerant THP-1 cells accumulated IL-1beta mRNA and protein with similar delayed
      kinetics. Okadaic acid stabilization of IL-1beta mRNA appears to be the primary
      mechanism through which endotoxin-tolerant cells accumulate IL-1beta mRNA and
      protein. Endotoxin-tolerant cells were unable to activate transcription in
      response to okadaic acid. However, the transcription factor NF-kappaB, which is
      known to be involved in IL-1beta expression, was translocated to the nucleus in
      both normal and endotoxin-tolerant cells after treatment with okadaic acid. These
      studies revealed that protein phosphorylation can affect gene expression on at
      least two distinct levels, transcription factor activation and mRNA stability.
      Endotoxin-tolerant cells have decreased transcription activation potential, while
      IL-1beta mRNA stability remains responsive to protein phosphorylation.

PMID- 9605978
TI  - Specific antibodies in sera and gastric aspirates of symptomatic and asymptomatic
      Helicobacter pylori-infected subjects.
AB  - In this study we have determined systemic and local antibody responses against
      different Helicobacter pylori antigens in H. pylori-infected and noninfected
      subjects. In addition, we studied whether differences in antibody responses
      between patients with duodenal ulcers and asymptomatic H. pylori carriers might
      explain the different outcomes of infection. Sera and in most instances gastric
      aspirates were collected from 19 duodenal ulcer patients, 15 asymptomatic H.
      pylori carriers, and 20 noninfected subjects and assayed for specific antibodies
      against different H. pylori antigens, i.e., whole membrane proteins (MP),
      lipopolysaccharides, flagellin, urease, the neuraminyllactose binding
      hemagglutinin HpaA, and a 26-kDa protein, by enzyme-linked immunosorbent assay.
      The H. pylori-infected subjects had significantly higher antibody titers against
      MP, flagellin, and urease in both sera and gastric aspirates compared with the
      noninfected subjects. Furthermore, the antibody titers against HpaA were
      significantly elevated in sera but not in gastric aspirates from the infected
      subjects. However, no differences in antibody titers against any of the tested
      antigens could be detected between the duodenal ulcer patients and the
      asymptomatic H. pylori carriers, either in sera or in gastric aspirates.

PMID- 9605980
TI  - Differentiation of F18ab+ from F18ac+ Escherichia coli by single-strand
      conformational polymorphism analysis of the major fimbrial subunit gene (fedA).
AB  - Toxin-producing Escherichia coli expressing F18 fimbriae colonizes the small
      intestines of weaned pigs and causes diarrhea, edema disease, or both. The F18
      family is composed of two antigenic variants, F18ab and F18ac. Because many
      strains do not express F18 fimbriae in vitro, identification and differentiation
      of these two variants are difficult. Single-strand conformational polymorphism
      (SSCP) analysis is a rapid method for identifying genetic mutations and
      polymorphisms. The F18 major fimbrial subunit genes (fedA) of 138 strains were
      amplified by PCR, and genetic differences were detected by SSCP analysis. The
      SSCP analysis of the fedA gene differentiated F18ab+ strains from F18ac+ strains.
      Most strains classified as F18ab+ by SSCP analysis contained Shiga toxin 2e and
      enterotoxin genes. Most strains classified as F18ac+ by SSCP analysis contained
      only enterotoxin genes. The SSCP analysis was a useful method for predicting the
      antigenicity of F18+ E. coli and could also be used for analysis of other
      virulence genes in E. coli and other pathogenic bacteria.

PMID- 9605979
TI  - Use of lytic bacteriophage for control of experimental Escherichia coli
      septicemia and meningitis in chickens and calves.
AB  - A lytic bacteriophage, which was previously isolated from sewage and which
      attaches to the K1 capsular antigen, has been used to prevent septicemia and a
      meningitis-like infection in chickens caused by a K1+ bacteremic strain of
      Escherichia coli. Protection was obtained even when administration of the phage
      was delayed until signs of disease appeared. The phage was able to multiply in
      the blood. In newly borne colostrum-deprived calves given the E. coli orally,
      intramuscular inoculation of phage delayed appearance of the bacterium in the
      blood and lengthened life span. With some provisos there is considerable
      potential for this approach to bacterial-disease therapy.

PMID- 9605981
TI  - Development and evaluation of a chromatographic procedure for partial
      purification of substance P with quantitation by an enzyme immunoassay.
AB  - We have developed a simple chromatographic procedure for the partial purification
      of substance P (SP) from acidified plasma and serum samples. We have evaluated a
      sensitive antigen competition enzyme immunoassay (EIA) for the quantitation of
      SP. The chromatographic procedure has recovery efficiencies ranging from 94.8 to
      125%. The immunoreactivity of unknown amounts of purified SP subjected to the
      preparative procedure yielded a coefficient of variance of 9.4%. The EIA yielded
      reproducible standard curves having an interassay (n = 8) correlation coefficient
      of 0.984. The evaluation of normal adult control serum yielded a mean value of 51
      pg/ml (range, 35 to 61 pg/ml). The evaluation of 3.33 x concentrates of serum
      derived partially purified SP provided uncorrected SP values of 117 to 201 pg/ml,
      which fell within the midpoint of the three-decalog standard curve. These studies
      indicate that both the preparative and quantitative procedures are required for
      the detection of SP in plasma or serum samples collected from patients with
      several clinical disorders.

PMID- 9605982
TI  - In vitro p24 antigen-stimulated lymphocyte proliferation and beta-chemokine
      production in human immunodeficiency virus type 1 (HIV-1)-seropositive subjects
      after immunization with an inactivated gp120-depleted HIV-1 immunogen (Remune).
AB  - We examined the effect of immune stimulation by a human immunodeficiency virus
      type 1 (HIV-1) immunogen (Remune) compared to a non-HIV vaccine (influenza) on
      HIV-1-specific immune responses in HIV-1-seropositive subjects. HIV-1 p24 antigen
      stimulated lymphocyte proliferation was not augmented after immunization with the
      influenza vaccine. In contrast, subjects increased their lymphocyte proliferative
      responses to p24 antigen after one immunization with HIV-1 immunogen (Remune)
      (gp120-depleted inactivated HIV-1 in incomplete Freund's adjuvant). Furthermore,
      p24 antigen-stimulated beta-chemokine production (RANTES, MIP-1alpha, MIP-1beta)
      was also augmented after immunization with the HIV-1 immunogen but not influenza
      vaccine. Taken together, these results suggest that in this cohort, HIV-specific
      immune responses to p24 antigen can be augmented after immunization with an HIV-1
      immunogen. The ability to upregulate immune responses to the more conserved core
      proteins may have important implications in the development of immunotherapeutic
      interventions for HIV-1 infection.

PMID- 9605983
TI  - Analysis of the humoral immune response to Chlamydia outer membrane protein 2.
AB  - The humoral immune response to Chlamydia outer membrane protein 2 (Omp2) was
      studied. Omp2 is a highly genus-conserved structural protein of all Chlamydia
      species, containing a variable N-terminal fragment. To analyze where the
      immunogenic parts were localized, seven highly purified truncated fusion proteins
      constituting different regions of the protein were produced (Chlamydia pneumoniae
      Omp2aa23-aa93, Chlamydia psittaci-Omp2aa23-aa94, and Chlamydia trachomatis
      Omp2aa23-aa84, aa87-aa547, aa23-aa182, aa167-aa434, aa420-aa547). By an enzyme
      linked immunosorbent assay with serologically defined patient sera, Omp2 was
      found to be a major immunogen of both C. pneumoniae and C. trachomatis infections
      (P < 0.0001). The humoral immune responses were not confined to any particular
      region of the Omp2 protein, and no species-specific anti-Omp2 immunoglobulins
      were detected.

PMID- 9605984
TI  - Association of low concentrations of serum mannose-binding protein with recurrent
      infections in adults.
AB  - Low concentrations of mannose-binding protein (MBP; also known as mannose-binding
      lectin) are associated with common opsonic defect in immunodeficient children. We
      compared the concentrations of MBP in the sera of 47 adults with non-human
      immunodeficiency virus-related recurrent infections (group I) and 50 healthy
      adult controls. Mean serum MBP concentrations in the patient group did not differ
      significantly from those in the control group (P < 0.4). Nevertheless, the
      proportion of individuals with less than 5 ng of serum MBP per ml was
      significantly larger in the patient group (21%, P = 0.01) than in the control
      group (4%). Group II consisted of 73 pediatric and 56 adult patients with
      recurrent infections. Pediatric patients had significantly lower mean
      concentrations of serum MBP than their controls (P < 0.005), and there was no
      significant difference between the concentrations in sera of adult patients and
      adult controls (P < 0.4). Again, the proportion of individuals with less than 5
      ng of serum MBP per ml was significantly larger in both pediatric (22%, P =
      0.045) and adult (38%, P = 0.000016) patients than in their respective controls
      (4%). Our results demonstrate that, as in children, low concentrations of serum
      MBP can be associated with recurrent infections in adults.

PMID- 9605985
TI  - The polysaccharide fucoidin inhibits the antibiotic-induced inflammatory cascade
      in experimental pneumococcal meningitis.
AB  - There is evidence that the treatment of bacterial meningitis with antibiotics
      liberates harmful bacterial products in the subarachnoid space (SAS). This
      enhances meningeal inflammation and in particular the recruitment of leukocytes
      into the cerebrospinal fluid (CSF), which has been shown to be more harmful than
      beneficial in this disease. In this study, we used a rabbit meningitis model
      based on intracisternal injection of live Streptococcus pneumoniae. Ampicillin
      (40 mg/kg of body weight given intravenously [i.v.] 16 h after induction of
      meningitis) caused a fivefold increase in CSF leukocytes over a 4-h period.
      Inhibition of leukocyte rolling by treatment with the polysaccharide fucoidin (10
      mg/kg, i.v.) prevented the enhanced leukocyte extravasation into the SAS and
      attenuated the leakage of plasma proteins over the blood-brain barrier. These
      results suggest that certain polysaccharides that block leukocyte rolling have
      the potential to reduce leukocyte-dependent central nervous system damage in
      bacterial meningitis.

PMID- 9605986
TI  - Serological, hematologic, and PCR studies of cattle in an area of Switzerland in
      which tick-borne fever (caused by Ehrlichia phagocytophila) is endemic.
AB  - The purpose of this study was to examine the seasonal variations in
      seroprevalence to Ehrlichia phagocytophila in cattle pastured during the summer
      months in an area where tick-borne fever is endemic. The study was performed
      during a 1-year period from April 1996 to March 1997 and involved 34 cows, 22
      pregnant heifers, and 14 calves. Blood samples, collected from all 70 cattle once
      a month, were used to determine serum immunoglobulin G titers by indirect
      immunofluorescence. In addition, blood smears were examined for Ehrlichia
      organisms, and PCR amplification was performed for the molecular detection of E.
      phagocytophila. Prior to the pasture period, the seroprevalence was 16%. Two
      weeks after the start of pasturing, it was 43%, after which it progressively
      increased and reached a maximum of 63% in September. The seroprevalence
      progressively decreased after the end of pasturing to a low of 23%. The variation
      in antibody titers was similar to that of seroprevalence. E. phagocytophila
      organisms were detected in blood smears of 7 animals and by nested PCR in 12.
      Only four cows, which were on the pastures of endemicity for the first time, had
      clinical signs of ehrlichiosis. This study demonstrated marked seasonal
      variations in seroprevalence and in serum titers of antibody to E. phagocytophila
      in cattle. The incidence of clinical signs of ehrlichiosis was increased in
      cattle grazing on the pastures of endemicity for the first time.

PMID- 9605988
TI  - Cytokine gene expression in normal human lymphocytes in response to stimulation.
AB  - Sequential gene expression of two type 1 cytokines (interleukin 2 [IL-2] and
      gamma interferon), one type 2 cytokine (IL-10), two monokines (IL-6 and tumor
      necrosis factor alpha), and one cytokine receptor (IL-2 receptor [IL-2R]) in
      normal human peripheral blood mononuclear cells (PBMC) following in vitro
      stimulation was investigated by reverse transcription-PCR methods. Two stimuli
      were utilized: phytohemagglutinin (PHA), which acts on the CD2 molecule and T
      cell receptors, and anti-CD3 monoclonal antibody, which acts on the CD3 molecule
      and on T-cell receptors. Increased expression of all studied genes occurred
      between 1 and 4 hours after stimulation, except for that of the gene encoding IL
      10, which was delayed. Expression of all but one of the genes was transient, with
      a maximal mRNA accumulation at about 8 h on average. IL-2R mRNA expression was an
      exception, showing a prolonged increase (72 h). The general profiles of
      expression of the five cytokine genes were similar but not identical, suggesting
      some shared regulatory mechanisms. When responses to four additional stimuli
      (pokeweed mitogen, Candida albicans, and IL-2 at high and low doses) were
      compared, similar profiles of cytokine gene expression were found. Thus, the
      various stimuli caused induction of all cytokines with quantitative, not
      qualitative, differences. Altogether, the present data are useful for defining
      the kinetics of gene expression for key cytokines in response to standard immune
      cell stimuli.

PMID- 9605987
TI  - Serotype specificity of the neutralizing-antibody response induced by the
      individual surface proteins of rotavirus in natural infections of young children.
AB  - The relative contribution of the rotavirus surface proteins, VP4 and VP7, to the
      induction of homotypic as well as heterotypic neutralizing antibodies (NtAbs) in
      natural infections was studied. The NtAb titers of paired sera from 70 infants
      with serologically defined primary rotavirus infections were determined with a
      panel of rotavirus reassortants having one surface protein from a human rotavirus
      (serotypes G1 to G4 for VP7 and P1A and P1B for VP4) and the other surface
      protein from a heterologous animal rotavirus strain. A subset of 37 children were
      evaluated for epitope-specific antibodies to the two proteins by an epitope
      blocking assay. The infants were found to seroconvert more frequently to VP4 than
      to VP7 by both methods, although the titers of the seroconverters were higher to
      VP7 than to VP4. Both proteins induced homotypic as well as heterotypic NtAbs. G1
      VP7 frequently induced a response to both G1 and G3 VP7s, while G3 VP7 and P1A
      VP4 induced mostly homotypic responses.

PMID- 9605989
TI  - Granulocyte-macrophage colony-stimulating factor amplification of interleukin
      1beta and tumor necrosis factor alpha production in THP-1 human monocytic cells
      stimulated with lipopolysaccharide of oral microorganisms.
AB  - Cytokines, including granulocyte-macrophage colony-stimulating factor (GM-CSF),
      are used to assist in bone marrow recovery during cancer chemotherapy.
      Interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) play
      important roles in inflammatory processes, including exacerbation of periodontal
      diseases, one of the most common complications in patients who undergo this
      therapy. A human monocyte cell line (THP-1) was utilized to investigate IL-1beta
      and TNF-alpha production following GM-CSF supplementation with lipopolysaccharide
      (LPS) from two oral microorganisms, Porphyromonas gingivalis and Fusobacterium
      nucleatum. LPS of P. gingivalis or F. nucleatum was prepared by a phenol-water
      extraction method and characterized by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and determination of total protein and endotoxin contents.
      Resting THP-1 cells were treated with LPS of P. gingivalis or F. nucleatum and/or
      GM-CSF (50 IU/ml) by using different concentrations for various time periods.
      Production of IL-1beta and TNF-alpha in THP-1 cells was measured by solid-phase
      enzyme-linked immunosorbent assay. Reverse transcription (RT)-PCR was used to
      evaluate the gene expression of resting and treated THP-1 cells. IL-1beta was not
      detected in untreated THP-1 cells. IL-1beta production was, however, stimulated
      sharply at 4 h. GM-CSF amplified IL-1beta production in THP-1 cells treated with
      LPS from both oral anaerobes. No IL-1beta-specific mRNA transcript was detected
      in untreated THP-1 cells. However, IL-1beta mRNA was detected by RT-PCR 2 h after
      stimulation of THP-1 cells with LPS from both organisms. GM-CSF did not shorten
      the IL-1beta transcriptional activation time. GM-CSF plus F. nucleatum or P.
      gingivalis LPS activated THP-1 cells to produce a 1.6-fold increase in TNF-alpha
      production at 4 h over LPS stimulation alone. These investigations with the in
      vitro THP-1 model indicate that there may be an increase in the cellular immune
      response to oral endotoxin following GM-CSF therapy, as evidenced by production
      of the tissue-reactive cytokines IL-1beta and TNF-alpha.

PMID- 9605990
TI  - Correlation between serological and sequencing analyses of the PorB outer
      membrane protein in the Neisseria meningitidis serotyping system.
AB  - The current serological typing scheme for Neisseria meningitidis is not
      comprehensive; a proportion of isolates are not serotypeable. DNA sequence
      analysis and predicted amino acid sequences were used to characterize the
      structures of variable-region (VR) epitopes on N. meningitidis PorB proteins
      (PorB VR typing). Twenty-six porB gene sequences were obtained from GenBank and
      aligned with 41 new sequences. Primary amino acid structures predicted from those
      genes were grouped into 30 VR families of related variants that displayed at
      least 60% similarity. We correlated VR families with monoclonal antibody (MAb)
      reactivities, establishing a relationship between VR families and epitope
      locations for 15 serotype-defining MAbs. The current panel of serotype-defining
      MAbs underestimates by at least 50% the PorB VR variability because reagents for
      several major VR families are lacking or because a number of VR variants within
      some families are not recognized by serotype-defining MAbs. These difficulties,
      also reported for serosubtyping based on the PorA protein, are shown as
      inconsistent results between serological and sequence analyses, leading to
      inaccurate strain identification and incomplete epidemiological data. The
      information from this study enabled the expansion of the panel of MAbs currently
      available for serotyping, by including MAbs of previously undetermined
      specificities. Use of the expanded serotype panel enabled us to improve the
      sensitivity of serotyping by resolving a number of formerly nonserotypeable
      strains. In most cases, this information can be used to predict the VR family
      placement of unknown PorB proteins without sequencing the entire porB gene. PorB
      VR typing complements serotyping, and a combination of both techniques may be
      used for full characterization of meningococcal strains. The present work
      represents the most complete and integrated data set of PorB VR sequences and MAb
      reactivities of serogroup B and C meningococci produced to date.

PMID- 9605991
TI  - The tumor necrosis factor-inducing potency of lipopolysaccharide and uronic acid
      polymers is increased when they are covalently linked to particles.
AB  - Lipopolysaccharide (LPS) and polymers of the uronic acid family stimulate
      monocytes to produce tumor necrosis factor (TNF). The TNF-inducing potency of
      these polysaccharides may depend on their supramolecular configuration. In this
      study detoxified LPS and uronic acid polymers have been covalently linked to
      particles which have been added to monocytes under serum-free conditions.
      Reducing the size of mannuronan from 350,000 to 5,500 Da (M-blocks) led to a 10-
      to 100-fold reduction in TNF-inducing potency. However, covalently linking the M
      blocks to monodisperse suspensions of magnetic particles increased the TNF
      inducing potency by up to 60,000-fold. Also, the TNF-inducing potency of
      glucuronic acid polymers was increased when they were linked to particles, but no
      potentiation was observed with guluronic acid blocks covalently attached to
      particles. Furthermore, O chains of LPS (detoxified LPS) became potent TNF
      inducers when they were presented to monocytes on a particle surface. No
      activation of the LPS-responsive SW480 adenocarcinoma cells was found with
      detoxified LPS or M-block particles, suggesting a preference for cells expressing
      CD14 and/or other membrane molecules. The potentiating effects were not
      restricted to polymers attached to aminated magnetic particles. Of particular
      interest, we found that short blocks of mannuronan induced TNF production also
      when covalently linked to biodegradable, bovine serum albumin particles.

PMID- 9605992
TI  - Multicolor cytoenzymatic evaluation of dipeptidyl peptidase IV (CD26) function in
      normal and neoplastic human T-lymphocyte populations.
AB  - Dipeptidyl peptidase IV (DPP IV), also identified as the glycoprotein CD26, is a
      transmembrane 110- to 120-kDa serine aminopeptidase involved in immune responses
      by influencing T-cell costimulation and by cleaving cytokines. Additionally, CD26
      is a nonintegrin receptor that contains a binding site for extracellular matrix
      and other molecules. In order to further define the expression and functional
      activity of this membrane exopeptidase in human T cells, we developed a
      nondisruptive, four-color cytofluorogenic assay that utilizes three separate
      antibodies to cell-surface molecules (e.g., CD4/CD8/CD26 and CD19/CD56/CD26)
      along with a rhodamine 110-conjugated dipeptide substrate that allows the
      measurement of DPP IV activity in phenotypically defined cells. We found normal
      human thymi to have notable differences in time-dependent DPP IV activity among
      the thymocyte subsets defined by their CD4/CD8 phenotype, with CD4-/CD8-
      thymocytes containing less DPP IV activity than cells expressing CD4 and/or CD8
      (i.e., maturing). CD26 positivity was moderately intense in thymocytes and tended
      to identify cells with higher DPP IV activity. The four-color technique was also
      used to examine mature peripheral blood lymphocytes, along with an assortment of
      leukemias and transformed T-cell lines. These experiments revealed that while DPP
      IV was consistently evident in normal T cells, neoplastic T cells could vary in
      their expression patterns. Furthermore, the presence (or intensity) of surface
      CD26 in some abnormal T cells and certain normal peripheral blood mononuclear
      cells was separable from the level of DPP IV measured intracellularly. Our
      results established that multicolor cytofluorographic analysis can be a practical
      means to measure DPP IV activity in various human cell populations. Furthermore,
      we found that DPP IV activity could vary in T cells according to their
      differentiation status and that under certain circumstances surface CD26
      expression can be disassociated from the level of measured enzyme (i.e., DPP IV)
      activity.

PMID- 9605993
TI  - Detection of antibodies to Candida albicans germ tubes during experimental
      infections by different Candida species.
AB  - Identification and characterization of Candida albicans germ tube-specific
      antigens may be of relevance for the serodiagnosis of invasive candidiasis since
      they could be the basis for the development of new diagnostic tests. In this
      study, we have identified two antigens of 180 and >200 kDa in the cell wall of C.
      albicans germ tubes which are responsible for the induction of antibodies to C.
      albicans germ tubes. Antigens of similar molecular masses have been demonstrated
      in the cell walls of the Candida species C. stellatoidea, C. parapsilosis, C.
      guilliermondii, C. tropicalis, and C. krusei, but not C. glabrata. The kinetics
      of the antibody responses to C. albicans germ tubes were studied in rabbits
      infected with different Candida species. Although these antibodies were detected
      in rabbits infected with all Candida species except C. glabrata, the kinetics of
      the antibody responses to C. albicans germ tubes induced by the Candida species
      studied were different. Both the highest titer and the earliest response of
      antibodies to C. albicans germ tubes were observed in rabbits infected with
      either of the two serotypes of C. albicans used. However, the time needed to
      elicit the antibodies to C. albicans germ tubes can be reduced as the result of
      an anamnestic antibody response. The results presented in this study show that a
      test designed to detect antibodies against C. albicans germ tube antigens may be
      suitable for the diagnosis of infections caused by most of the medically
      important Candida species.

PMID- 9605994
TI  - Physiologic-chemoattractant-induced migration of polymorphonuclear leukocytes in
      milk.
AB  - The somatic cell count (SCC; leukocytes and epithelial cells) in milk is used as
      an indicator of udder health status. A SCC above the regulatory standard is
      generally considered as an indication of mastitis. Therefore, milk with a SCC
      equal to or greater than the regulatory limit cannot be sold to the public
      because it is unsuitable for human consumption. This study was performed to
      determine whether SCC levels above the regulatory limit observed in goats during
      late lactation are a physiologic or a pathological response of the goat mammary
      gland. Differential counts of cells in nonmastitic goat milk samples during late
      lactation revealed that approximately 80% of the cells were polymorphonuclear
      leukocytes (PMNs). In addition, microchemotaxis assay results indicated that
      normal nonmastitic late-lactation-stage goat milk is significantly higher (P <
      0.001) in PMN chemotactic activity than early-lactation-stage goat milk, with a
      mean chemotactic activity of 14.9 and 42.7/mg of protein for early and late
      lactation stages, respectively. Physicochemical analyses also suggest that the
      PMN infiltration observed in normal late-lactation-stage goat milk is due to a
      PMN chemotactic factor(s) that is different from the PMN chemotactic factor(s)
      present in mastitic milk. Interestingly, the PMN chemotactic factor in late
      lactation-stage goat milk is highly acid resistant (pH 2), suggesting that the
      factor is able to survive the highly acidic gastric environment and may therefore
      be important in the augmentation of the immune systems of sucklings. These
      results indicate that the chemotactic factor(s) present in the milk of normal
      late-lactation-stage goats is nonpathological and may play a physiologic
      regulatory role in mammary gland involution. Hence, the regulatory standard for
      goat milk needs to be redefined in order to reflect this.

PMID- 9605995
TI  - A bereavement support group intervention is longitudinally associated with
      salutary effects on the CD4 cell count and number of physician visits.
AB  - A randomized, controlled, clinical trial was conducted to examine the impact of a
      semistructured, 10-week, once weekly, 90-min/session bereavement support group
      intervention on immunological, neuroendocrine, and clinical health status in
      human immunodeficiency virus type 1-seropositive (HIV-1+) and HIV-1-seronegative
      (HIV-1-) homosexual men, compared to a standard of care control condition. A
      total of 119 homosexual men (74 HIV-1+ and 45 HIV-1-) were assessed at baseline,
      10 weeks, and 6 months follow-up. At the 6-month follow-up assessment, the
      intervention groups exhibited significant beneficial effects compared to controls
      on changes in CD4 cell, total T-lymphocyte, and total lymphocyte counts, when
      baseline levels, antiretroviral medication use, CDC stage of disease, and other
      potentially confounding factors were accounted for. There was no statistically
      significant effect on the CD4/CD8 ratio or on the CD8 cell count. The effect on
      CD4 cell count was associated with group attendance and with changes in plasma
      cortisol level. Plasma cortisol levels decreased significantly among intervention
      subjects, compared to controls. A significantly reduced number of health care
      visits over the 6-month follow-up period among the intervention subjects
      supported the clinical relevance of the immunological changes observed for both
      HIV-1+ and HIV-1- individuals. These results indicate that behavioral
      interventions may have salutary immunological and clinical health effects
      following bereavement among HIV-1-infected individuals. The effect in HIV-1-
      individuals suggests that this bereavement support group intervention might have
      similar salutary effects in the general population. Potential effects of such
      interventions on clinical HIV disease progression are of interest and should be
      studied.

PMID- 9605996
TI  - A whole-blood assay for qualitative and semiquantitative measurements of CD69
      surface expression on CD4 and CD8 T lymphocytes using flow cytometry.
AB  - A whole-blood flow cytometry-based assay was utilized to assess CD4 and CD8 T
      lymphocyte activation in response to phytohemagglutinin (PHA) stimulation. T
      lymphocyte activation was assessed by qualitative (percent CD69) and
      semiquantitative (anti-CD69 antibody binding capacity) measurements of CD69
      surface expression. Whole-blood samples from 21 healthy and 21 human
      immunodeficiency virus (HIV)-infected (<500 absolute CD4 counts per mm3)
      individuals were stimulated with 20 microg of PHA per ml for 18 to 24 h. The
      proportions of activated CD4 and CD8 T lymphocytes expressing CD69 (percent CD69)
      and the levels of CD69 expression on each T-lymphocyte subset (anti-CD69 antibody
      binding capacity) were measured. By using this assay system, T-lymphocyte
      activation was impaired in both CD4 and CD8 T-lymphocyte subsets of HIV-infected
      individuals. The proportions of CD69-positive CD4 and CD8 T lymphocytes were 43
      and 27% lower, respectively, in samples from HIV-infected individuals compared to
      samples from healthy individuals. Similarly, the levels of CD69 expression on
      each activated CD4 and CD8 T-lymphocyte subset were 48 and 51% lower,
      respectively. These results suggest that both qualitative and semiquantitative
      measurements of CD69 surface expression by flow cytometry can be used to assess T
      lymphocyte activation.

PMID- 9605997
TI  - Adenosine deaminase deficiency and purine nucleoside phosphorylase deficiency in
      common variable immunodeficiency.
AB  - The clinical presentations of adenosine deaminase deficiency and purine
      nucleoside phosphorylase deficiency are widely variable and include clinical and
      immunologic findings compatible with common variable immunodeficiency. The
      screening of 44 patients with common variable immunodeficiency failed to identify
      any individuals with deficiencies of these enzymes.

PMID- 9605998
TI  - Serum cytokines in patients with Legionella pneumonia: relative predominance of
      Th1-type cytokines.
AB  - Serum samples from 14 patients with Legionella pneumonia were examined for the
      presence of cytokines. In spite of high levels of serum C-reactive protein in all
      patients during the acute phase in only four cases (one involving interleukin
      1beta [IL-1beta], three involving IL-6, and none involving tumor necrosis factor
      alpha) was the concentration of cytokines more than 100 pg/ml. Th2 cytokines IL-4
      and IL-10 were detected in only one patient each. In contrast, significant
      increases of serum gamma interferon (IFN-gamma) and IL-12 levels were observed
      during the acute phase in 6 and 11 cases, respectively. Interestingly, although
      serum IFN-gamma levels diminished thereafter, in seven cases IL-12 levels
      remained high or increased further during the convalescent phase. In an
      additional 22 cases clinically suspected to be but not diagnosed as Legionella
      pneumonia, increases of serum IL-12 levels were observed in 16 cases, whereas the
      remaining 6 cases showed no detectable IL-12. Our results demonstrate the
      relative predominance of Th1 cytokine production in Legionella pneumonia.
      Although the role and significance of prolonged increases in IL-12 levels in
      Legionella disease are unknown, our results should prompt further investigation
      of the host immune response in terms of Th1 and Th2 balance in legionellosis.

PMID- 9605999
TI  - Primary epitopes of chicken egg yolk antibodies to peptidophosphogalactomannan.
AB  - Egg yolks from hens immunized with peptidophosphogalactomannan (pPGalMan(ii)),
      which contains 10 phosphocholine diester residues and is secreted by Penicillium
      fellutanum, contain antibodies against 5-O-beta-D-galactofuranosyl epitopes.
      These epitopes were the only significant determinants in pPGalMan(ii).
      Approximately 60-fold less pPGalMan(ii) (1.6 microM galactofuran chains) was
      required for 50% inhibition than galactofurano-oligosaccharides or pPGalMan
      containing two galactofuranosyl residues per chain.

PMID- 9606000
TI  - Clinical evaluation of a rapid immunochromatographic test for the diagnosis of
      dengue virus infection.
AB  - A rapid immunochromatographic test was compared to the hemagglutination
      inhibition assay for separate determinations of dengue virus-specific
      immunoglobulin M (IgM) and IgG levels in paired serum specimens from 92 patients
      (34 with primary dengue virus infection, 35 with secondary dengue virus
      infection, and 23 without dengue virus infection). The rapid test showed 99%
      sensitivity in the diagnosis of dengue virus infection. The majority (30 of 34
      [88%]) of patients with primary infection showed positive IgM but negative IgG,
      while 34 of 35 (97%) patients with secondary infection showed positive IgG with
      or without IgM. Specificity in nonflavivirus infections was 96% (1 of 23
      positive). The rapid test should be a useful aid in rapid diagnosis of dengue
      virus infection.

PMID- 9606001
TI  - Effect of cytokines on anticryptococcal activity of human microglial cells.
AB  - The effect of selected cytokines on the antifungal activity of human microglia
      was studied with encapsulated and acapsular strains of Cryptococcus neoformans.
      None of the cytokines tested increased the fungistatic activity of microglia,
      suggesting that killing of cryptococci within the central nervous system is
      dependent on other host defense mechanisms.

PMID- 9606002
TI  - Immunohistochemical detection of porcine epidemic diarrhea virus compared to
      other methods.
AB  - An immunohistochemistry method using formalin-fixed tissues, a direct
      immunofluorescence method using cryostat sections, an enzyme-linked immunosorbent
      assay (ELISA), and a PCR method were compared for diagnosis in a litter of weaned
      pigs that had been experimentally inoculated with wild-type porcine epidemic
      diarrhea virus (PEDV) and killed between 6 and 60 h after onset of diarrhea. The
      immunohistochemistry method proved to be as reliable as direct immunofluorescence
      for diagnosis of PEDV in tissues collected postmortem. The good reliability of
      ELISA for investigating clinical samples was confirmed, whereas the PCR method
      used was ineffective.

PMID- 9606003
TI  - Increased prevalence of immunoglobulin A deficiency in patients with the
      chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial
      syndrome).
AB  - We wished to determine the prevalence of immunoglobulin A (IgA) deficiency in
      patients with the chromosome 22q11.2 deletion syndrome. A total of 32 patients
      with the chromosome 22q11.2 deletion were examined for IgA deficiency. We report
      a 13% (n = 4) prevalence of IgA deficiency in patients with this syndrome. The
      odds ratio of IgA deficiency in this population is 14.20 (P < 0.0001). This
      confirms the occurrence of significant humoral deficits in this predominantly
      cellular immunodeficiency.

PMID- 9606004
TI  - Recent antibody targeting technologies--a survey of the patent literature.

PMID- 9606005
TI  - Structural requirements for cationic lipid mediated phosphorothioate
      oligonucleotides delivery to cells in culture.
AB  - A series of 2,3-dialkyloxypropyl quaternary ammonium lipids containing
      hydroxyalkyl chains on the quaternary amine were synthesized, formulated with
      dioleoylphosphatidylethanolamine (DOPE) and assayed for their ability to enhance
      the activity of an intercellular adhesion molecule 1 (ICAM-1) antisense
      oligonucleotide, ISIS 1570. Cationic liposomes prepared with hydroxyethyl,
      hydroxypropyl and hydroxybutyl substituted cationic lipid all enhanced the
      activity of the ICAM-1 antisense oligonucleotide. Cationic lipids containing
      hydroxypentyl quaternary amines only marginally enhanced the activity of ISIS
      1570. Hydroxyethyl cationic lipids synthesized with dimyristyl (Cl4:0) and
      dioleyl (C18:1) alkyl chains were equally effective. Activity of cationic lipids
      containing saturated alkyl groups decreased as the chain length increased, i.e.
      the dimyristyl (C14:0) was more effective than dipalmityl (C16:0) lipid, which
      was more effective than distearyl (C18:0). The phase transition temperature of
      cationic lipids containing saturated aliphatic chains was 56 degrees C for the
      distearyl lipid, 42 degrees C for the dipalmityl lipid and 24 degrees C for the
      dimyristyl lipid. Cationic lipids with dioleyl alkyl chains required DOPE for
      activity, with optimal activity occurring at 50 mole%. In contrast, a dimyristyl
      containing cationic lipid did not require DOPE to enhance the activity of ISIS
      1570. Formulation with different phosphatidylethanolamine derivatives, revealed
      that optimal activity was obtained with DOPE. These studies demonstrate that
      several cationic lipid species enhance the activity of phosphorothioate antisense
      oligonucleotides and provide further information on the mechanism by which
      cationic lipids enhance the activity of phosphorothioate oligodeoxynucleotides.

PMID- 9606006
TI  - Nuclear localization signal peptides enhance cationic liposome-mediated gene
      therapy.
AB  - The use of genes as therapeutic drugs will likely involve non-viral delivery
      systems. While traditionally less effective for gene expression, the advantages
      of a non-viral delivery system include ease of production, lower toxicity, and no
      risk of infection. However, most non-viral systems do not incorporate a mechanism
      for gene transport into the nucleus. Nuclear localization signal peptides can
      combine the increased expression of viral delivery systems with the safety and
      ease of preparation of non-viral delivery systems. A novel non-viral delivery
      vehicle consisting of a conglomerate of a synthetic nuclear localization signal
      peptide derived from the SV40 virus, a luciferase encoding PGL3 plasmid, and a
      cationic lipid DOTAP:DOPE (1:1 w/w) liposome was transfected into SKnSH mammalian
      neuroblastoma cells. A three-fold increase in luciferase expression was seen with
      the delivery system containing a NLS peptide over cationic liposome controls.
      Examination of the factors that limit the rate of transgene expression can
      potentially lead to the discovery of new ways to improve the efficiency and
      efficacy of nonviral methods of gene therapy.

PMID- 9606007
TI  - Improved body distribution of 14C-labelled AZT bound to nanoparticles in rats
      determined by radioluminography.
AB  - The objective of the present study is to visualize differences in the body
      distribution between radiolabelled AZT bound to nanoparticles and a control
      solution. Polyhexylcyanoacrylate nanoparticles were manufactured by emulsion
      polymerization in the presence of AZT and an ionic emulsifier, bis(2-ethylhexyl)
      sulfosuccinate sodium. The AZT-control solution was equally prepared, but
      contained no monomer. The two preparations were administered either by i.v.
      injection or perorally by gavage. After determined time points the animals were
      sacrificed using carbon dioxide. The cadavers were shock-frozen in cellulose gel
      and cut into slices using a cryomicrotome. The tissue cross sections were fixed
      on an adhesive tape and then were freeze dried. The quantification of the
      radioactive AZT in the different organs and tissues was performed by
      radioluminography, and the images were generated on a computer. After i.v.
      injection of AZT-nanoparticles, a high amount of the AZT label was found in the
      organs belonging to the reticuloendothelial system. In these organs the
      radioactivity was inhomogeneously distributed showing that the uptake of the
      particle-associated radioactivity depended on the type of the cells located in
      the organs and was consistent with uptake by macrophages. The highest
      radioactivities were found in the GI-tract and in the liver. A difference in the
      elimination pathway between AZT-control solution and AZT bound to nanoparticles
      also was visible on the images. Similar results were obtained after oral
      administration. Of course, with the latter route a larger portion of AZT remained
      in the GI-tract especially after administration of nanoparticle-bound drug. These
      results confirmed those obtained by a classically performed quantitative whole
      body distribution study using liquid scintillation. This demonstrates that
      radioluminography is a useful method to study the organ distribution of drugs
      bound to nanoparticles.

PMID- 9606008
TI  - Different sensitivity of CD30+ cell lines to Ber-H2/saporin-S6 immunotoxin.
AB  - The in vitro sensitivity of cells to a Ber-H2(anti-CD30)/saporin-S6 immunotoxin
      has been investigated. The CD30+ cell lines, K562, L428 and L540, were used to
      study cell binding, uptake and degradation of the immunotoxin. K562 cells were
      less sensitive than L428 and L540 cells to the immunotoxin by approximately one
      order of magnitude. The difference in cytotoxicity correlated with the
      intracellular accumulation and with the ratio of degraded over total internalized
      Ber-H2/saporin-S6, regardless of the immunotoxin binding to the cells. After 6 h
      incubation, the less sensitive K562 cells (i) accumulated only one third and one
      tenth of the immunotoxin accumulated by the more sensitive L428 and L540 cells,
      respectively, and (ii) degraded two thirds of the internalized protein versus one
      third degraded by either L428 or L540 cells. Ammonium chloride and chloroquine
      reduced the cytotoxicity of the immunotoxin towards K562 but not to L540 cells.
      This effect correlated with the increment of immunotoxin catabolism by K562 cells
      in the presence of chloroquine. In conclusion, uptake alone of an immunotoxin by
      target cells is not sufficient to assure its efficacy which might also depend on
      intracellular routing. Only a cytotoxicity test may be really predictive.

PMID- 9606009
TI  - Uptake and intracellular distribution of 4-aminofluorescin-labelled poly(L-lysine
      citramide imide) in K562 cells.
AB  - 4-Aminofluorescein (F1-NH2) was conjugated with various macromolecular carriers
      of the poly(L-lysine citramide)-type which were hydrophobised by ethyl (C2),
      heptyl (C7), and dodecyl (C12) alkyl groups attached to the pendent carboxyl of
      the lysine moieties present in repeating units. The dye was used to label the
      carriers and monitor their intracellular fate after introduction within the
      incubation medium of K562 cells. The labelled hydrophobised carriers formed
      multimolecular compacted aggregates stabilised by the balance of attractive
      hydrophobic interactions and repulsive electrostatic forces in the aqueous
      culture medium. The apparent molecular weights and the sizes of these aggregates
      were determined by Size Exclusion Chromatography (SEC) and by light scattering
      respectively. Comparison was made of the cell distribution of free and conjugated
      F1-NH2 in the cell cytoplasm and nucleus by using fluorescence microscopy and
      laser microspectrofluorometry. It was shown that cell uptakes resulted from
      adsorptive pinocytosis and depended on hydrophobicity and aggregation of the
      conjugates. The influence of physical entrapment of free-F1-NH2 within the
      hydrophobic microdomains formed by aggregates F1-NH2 conjugates was also
      discussed.

PMID- 9606010
TI  - Different transfers of N-acetyl-p-aminobenzoic acid and p-aminobenzoic acid
      across the placenta and the small intestine in rats.
AB  - The aim of the present study was to evaluate the transfer of N-acetyl-p
      aminobenzoic acid (AcPABA) across the rat term placenta and the rat small
      intestine and to compare it with that of its parent drug p-aminobenzoic acid
      (PABA). Umbilical perfusion of the rat term placenta was used to determine the
      materno-fetal transfer. AcPABA appeared in the fetal compartment significantly
      more slowly than PABA (k transfer = 0.023 and 0.064 min(-1), respectively). The
      rate of equilibration between the maternal and fetal compartments was slightly
      lower for AcPABA than for the parent drug (k eqilibration = 0.0082 and 0.011 min(
      1), respectively). Similarly, AcPABA was shown to be absorbed from the small
      intestine significantly more slowly than PABA (ka = 0.052 and 0.82 min(-); tmax =
      37 and 3.1 min, respectively). Our results showed that both investigated
      compounds which are structurally related and very similar in their physical
      chemical characteristics crossed both the placental and small intestinal barrier
      with a different kinetics. AcPABA was transported across both barriers
      significantly more slowly than its parent compound, which might indicate a
      possible equipment of the placenta with a carrier for PABA, a similar one to that
      previously found in the rat small intestine.

PMID- 9606011
TI  - Absorption enhancement in intestinal epithelial Caco-2 monolayers by sodium
      caprate: assessment of molecular weight dependence and demonstration of transport
      routes.
AB  - Sodium caprate (C10), a medium chain fatty acid, is used clinically to enhance
      rectal absorption of the low molecular weight (MW) drug ampicillin. The main aim
      of this study was to investigate whether C10 also enhances the permeability of
      high MW model drugs in a model of the intestinal epithelium. The second aim was
      to present visual evidence of the route of enhanced transport across the
      epithelial cell layer. The studies were performed in Caco-2 monolayers cultured
      on permeable supports. The effects of non-toxic concentrations (< or = 13 mM) of
      C10 on drug transport across the monolayers was studied using monodisperse 14C
      polyethylene glycols (MW 238-502; 14C-PEGs), 125I-Arg5-vasopressin (MW 1,208),
      125I-insulin (MW 6,000) and FITC-labelled dextrans (MW 4,400 and 19,600; FD4 and
      FD20 respectively) as model drugs. Electron and confocal laser scanning
      microscopy were used to demonstrate transport routes across the epithelium. 10 mM
      C10 increased the permeability of all 14C-PEGs to approximately the same extent.
      13 mM C10 increased the permeability of 125I-Arg8-vasopressin 10-fold. Only small
      increases in FD4 and FD20 permeabilities were observed. After C10 exposure, both
      tight junctions with normal morphology and those with dilatations showed an
      increased permeability to ruthenium red, indicating that C10 enhanced the
      paracellular transport of molecules with a MW < 1,000. Confocal microscopy showed
      that C10 increased the transport of FD4 and FD20 by the paracellular route. In
      conclusion, non-toxic concentrations of C10 can be used to enhance the
      permeability of drugs of MW up to approximately 1,200. Enhancement of the
      absorption of molecules larger than 4,000 is quantitatively insignificant. The
      enhanced permeability occurred via the paracellular pathway.

PMID- 9606012
TI  - Synthesis of cyclic dipeptide templates, their incorporation into peptides and
      studies on their conformational and biological properties.
AB  - This study investigated the diastereoselective synthesis of three dipeptide
      templates 1, 2 and 3, which may be regarded as conformationally restricted
      analogs of H-Gly-Xaa-OH, in which Xaa constitutes an aromatic amino acid. Bond
      formation between alpha-C of Gly and the aromatic moiety was achieved by proton
      catalyzed intramolecular electrophilic aromatic substitution. The absolute
      configuration of the dipeptide templates was determined by single-crystal X-ray
      crystallography or by nuclear Overhauser enhancement measurements. A protective
      group strategy was elaborated to allow their incorporation into peptide sequences
      by liquid phase as well as by solid-phase peptide synthesis. The templates were
      used to generate an enkephalin analog 15, a modified peptidic neurokinin
      antagonist 20 and two dermorphin derivatives (24 and 33). Molecular dynamic
      simulations with 15 and 20 revealed the preference for a turn-like motif for 15.
      The biological activity, as investigated by respective receptor binding and
      functional assays, was strongly diminished with all four derivatives, indicating
      that their receptor-relevant molecular geometries lie outside the examined
      conformational space.

PMID- 9606013
TI  - Structure and property of model peptides of proline/arginine-rich region in
      bactenecin 5.
AB  - Bactenecin 5 (Bac 5), a cationic antibacterial peptide, contains a repeating
      region of Arg-Pro-Pro-X (X = hydrophobic residue). To investigate the structure
      and property of a Pro/Arg-rich region, we synthesized a series of repeating
      peptides, Ac-(Arg-Pro-Pro-Phe)n-NHCH3 (n = 2, 4, 6, 8 and 10) (PR2, PR4, PR6, PR8
      and PR10) as models. The circular dichroism (CD) study suggested that the
      peptides with longer repeats, PR6, PR8 and PR10, formed a conformation similar to
      poly(proline)-II in aqueous solution. The CD spectra did not change in the
      presence of dipalmitoyl-DL-alpha-phosphatidylcholine (DPPC), but they changed in
      the presence of DPPC/ dipalmitoyl-DL-3-phosphatidylglycerol (DPPG). The gamma
      helix, which is very similar in conformation to the poly(proline)-II helix, had
      the lowest energy conformation for the peptides by energy calculations. Peptides
      PR6, PR8 and PR10 caused slight leakage of fluorescent dye entrapped in DPPC
      vesicles, and in the presence of DPPC/DPPG, these peptides showed a considerable
      level of dye-leakage activity. In contrast, the shorter peptides PR2 and PR4
      showed no activity. The same tendency was found in measurements of membrane
      fusion activity. Judging from these results, the repeating region of Bac 5 may
      make a framework to hold a conformation resembling the poly(proline)-II structure
      in aqueous solution. In addition, this region may interact with acidic lipids,
      resulting in a change in conformation of the peptide.

PMID- 9606015
TI  - Chemical synthesis of dendrotoxin-I: revision of the reported structure.
AB  - Dendrotoxin I (DTX-I) is a 60-residue peptide from the venom of the black mamba
      snake Dendroaspis polylepis, which binds to neuronal K+ channels. The structure
      reported previously for DTX-I was synthesized for the first time by a solution
      procedure. The synthetic product was confirmed to have the correct primary and
      disulfide structure determined by peptide mapping, sequence analysis and mass
      measurements. Comparison of synthetic DTX-I with the natural one by high
      performance liquid chromatography and capillary zone electrophoresis, as well as
      by sequence analysis, revealed that the Asn residue at position 12 in the
      synthetic peptide was Asp in the natural product. Synthesis of DTX-I with Asp at
      position 12 gave a peptide identical with the natural product in all aspects. NMR
      analysis of synthetic [Asn12]- and [Asp12]-DTX-I also supported our findings that
      the Asn residue at position 12 in the DTX-I molecule should be revised as Asp.
      [Asn12]- and [Asp12]-DTX-I had very similar binding affinities when tested
      against radiolabeled dendrotoxin binding to rat brain synaptosomal membranes.

PMID- 9606014
TI  - Dipeptidyl aminotransferase activity and in vitro O-glycosylation of MUC5AC mucin
      motif peptides by human gastric microsomal preparations.
AB  - The in vitro O-glycosylation reaction of the MUC5AC mucin motif peptide, TTSAPTTS
      (in one-letter code), was achieved with human gastric microsomal homogenates. The
      analyses using capillary electrophoresis online coupled with electrospray mass
      spectrometry and further Edman degradation of the purified products (obtained by
      capillary electrophoresis at preparative scale) allowed us to distinguish two
      components at close masses: the addition of a mass of 202 corresponded to an N
      terminal elongation of the peptide TTSAPTTS with the dipeptide (TT) and the
      addition of a mass of 203 corresponded to an N-acetylgalactosamine O-linkage.
      Using different peptidase inhibitors, a dipeptidyl peptidase/transferase activity
      was further characterized. A thiol dependence and an inhibition by H-Gly-PheCHN2
      (specific to cathepsin C activity) were found. Moreover, besides TTSAPTTS, other
      MUC5AC motif peptides (GTTPSPVP, TSAPTTS) were also dipeptide donors (GT and TS,
      respectively) and our results suggested the involvement of a single dipeptidyl
      peptidase/transferase activity. Finally, this latter activity modified the in
      vitro GalNAc incorporation rates when using our selected MUC5AC motif peptides.
      Our study therefore shows that caution must be taken to prevent peptidic
      substrate elongation while performing in vitro O-glycosylation with microsomal
      preparations as the enzyme source. In fact, the results of the N
      acetylgalactosamine incorporation rates and thus the microsomal N
      acetylgalactosamine transferase affinity can be misinterpreted if dipeptidyl
      peptidase/transferase activity is not inhibited by the thiol inhibitor E-64 or
      the cathepsin C inhibitor H-Gly-PheCHN2.

PMID- 9606016
TI  - Charcoal surface-assisted catalysis of intramolecular disulfide bond formation in
      peptides.
AB  - A mild and highly efficient method for intramolecular disulfide bond formation in
      peptides mediated by charcoal has been developed. Completion of the charcoal
      assisted catalysis of disulfide bond formation took less than 6 h, testing a
      series of peptides with ring sizes varying from 2 to 17 amino acids. Kinetic
      studies revealed that the formation of small and large intramolecular disulfide
      cycles especially was accelerated significantly by the aid of charcoal as
      compared with dimethyl sulfoxide- and air-mediated cyclization. Oxygen adsorbed
      onto the charcoal surface is a prerequisite for disulfide bond formation.
      Thermodynamic studies showed that cyclization is accelerated by reduction of
      entropy of the peptides, most likely because of transient adsorption to the
      charcoal surface, thus resulting in a lower activation energy.

PMID- 9606017
TI  - Antigenicity of linear and cyclic peptides mimicking the disulfide loops in HIV-2
      envelope glycoprotein: synthesis, reoxidation and purification.
AB  - The external envelope glycoprotein (gp125) of human immunodeficiency virus type 2
      (HIV-2) contains 22 cysteine residues. The positions of the 11 disulfide bridges
      in HIV-2 gp125 were determined by analogy with the experimental position of the
      disulfide bonds found in the gp120 of HIV-1. Peptides expected to mimic all 11
      disulfide-bonded domains containing from 13 to 47 amino acids were synthesized by
      the solid-phase method according to 9-fluorenylmethoxycarbonyl strategy, except
      for peptide 5, which was assembled according to t-butoxycarbonyl (Boc) strategy.
      Analysis of all the crude peptides showed that the expected peptides were
      obtained with good yields, between 75% and 85%. Peptides were purified further by
      high-performance liquid chromatography (HPLC) on an Aquapore RPC30 C8 column.
      Peptide homogeneity was more than 90%. For each peptide, linear peptides (L) were
      SH-iodoacetamidated, whereas cyclization of peptides (C) was performed by air
      oxidation. Oxidation kinetics was followed with the Ellman test and HPLC. Cyclic
      peptides were purified by HPLC and characterized by fast atom bombardment mass
      spectrometry. This analysis showed that a small quantity (<10%) of dimeric
      peptides (2 and 8) and cyclic peptides containing oxidized methionine or
      tryptophan residues (4, 9 and 10) were formed. To assess the relevance of
      conformation for the antigenicity of disulfide-bonded loops of HIV-2 gp125, the
      antigenicity of linear and cyclic peptides was tested against a set of 76 HIV-2
      positive human sera by enzyme-linked immunosorbent assay. Peptides 2, 4 and 9,
      mimicking the V1, V2 and V3 regions of the external envelope glycoprotein (gp
      125) of HIV-2, were the most highly reactive with HIV-2 positive human sera
      tested at the dilution of 1:50. Cyclic peptides generally were recognized more
      than linear peptides, as shown by their greater inhibition (2 to 10 times more)
      of antigen-antibody complexes. Structure-antigenicity of peptide V3, the most
      reactive peptide (75% of the HIV-2 positive sera tested), was analyzed further.
      Cyclic peptide 9C had a higher affinity for anti-gp125 antibodies than linear
      peptide 9L. In addition, circular dichroism showed that linear and cyclic
      peptides 9 had a similar structure, but when analyzed in aqueous solution or in
      trifluoroethanol (TFE), the structural difference shown with antibodies was not
      confirmed. No significant difference was observed between the antigenicity of
      linear and cyclic peptides 1, 8 and 11, mimicking the C1, C2 and C4 regions of
      HIV-1 gp125. These peptides were weakly reactive with HIV-2 positive sera. This
      result agrees with the low immunogenicity of conserved regions.

PMID- 9606018
TI  - The receptor-bound conformation of H-Tyr-Tic-(Phe-Phe)-OH-related delta-opioid
      antagonists contains all trans peptide bonds.
AB  - Two different models for the receptor-bound conformation of delta-opioid peptide
      antagonists containing the N-terminal dipeptide segment H-Tyr-Tic (Tic = 1,2,3,4
      tetrahydroisoquinoline-3-carboxylic acid) have been proposed. Both models are
      based on spatial overlap of the Tyr1 and Tic2 aromatic rings and N-terminal amino
      group with the corresponding aromatic rings and nitrogen atom of the nonpeptide
      delta-antagonist naltrindole. However, in one model the peptide bond between the
      Tyr1 and Tic2 residues assumes the trans conformation, whereas in the other it is
      in the cis conformation. To distinguish between these two models, we prepared the
      two peptides H-Tyr(psi)[CH2NH]Tic-Phe-Phe-OH and H-Tyr(psi)[CH2NH]MeTic-Phe-Phe
      OH (MeTic = 3-methyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) in which a
      cis peptide bond between the Tyr and Tic (or MeTic) residues is sterically
      forbidden. Both compounds turned out to be moderately potent delta-opioid
      antagonists in the mouse vas deferens assay. A molecular mechanics study
      performed with both peptides resulted in low-energy conformations in which the
      torsional angle ("omega1") of the reduced peptide bond between Tyr and Tic (or
      MeTic) had a value of 180 degrees (trans conformation) and which were in good
      agreement with the proposed model with all trans peptide bonds. Furthermore, this
      study confirmed that neither of these two peptides could assume low-energy
      conformations in which "omega1" had a value of 0 degrees (cis conformation).
      Conformers with that same bond in the gauche conformation ("omega1" = -60
      degrees) were also identified, but were higher in energy and showed no spatial
      overlap with naltrindole. On the basis of these results it is concluded that the
      receptor-bound conformation of delta-peptide antagonists containing an N-terminal
      H-Tyr-Tic-dipeptide segment must have all trans peptide bonds.

PMID- 9606019
TI  - The M2 muscarinic receptor antagonist methoctramine activates mast cells via
      pertussis toxin-sensitive G proteins.
AB  - Methoctramine, a selective M2 muscarinic cholinergic receptor antagonist, has
      been reported to activate phosphoinositide breakdown at high concentrations. Its
      polyamine structure suggests a putative activation of guanine nucleotide-binding
      proteins (G proteins). Incubation of methoctramine with rat peritoneal mast cells
      resulted in a dose-dependent noncytotoxic histamine release, with an EC50 of 20
      microM and a maximum effect at 1 mM. Atropine, pirenzepine and HHSiD neither
      inhibited methoctramine-induced histamine release nor stimulated histamine
      release. Histamine release and inositol phosphates generation induced by
      methoctramine were both inhibited by pertussis toxin pretreatment. Benzalkonium
      chloride, a selective inhibitor of histamine secretion induced by basic
      secretagogues, inhibited the secretory response to methoctramine. [p-Glu5, D
      Trp7,9,l0]-SPs5-11 (GPAnt-2), a well-characterized antagonist of G proteins,
      blocked the methoctramine-induced histamine release when the antagonist was
      allowed to reach its intracellular target by streptolysin O-permeabilization. The
      response to methoctramine was prevented by the hydrolysis of sialic acid residues
      of the cell surface by neuraminidase. The response of mast cells was restored by
      permeabilization of the plasma membrane. These results demonstrate that
      methoctramine, following its entry into the cell and the involvement of pertussis
      toxin-sensitive G proteins, activates phosphoinositide hydrolysis leading to mast
      cell exocytosis.

PMID- 9606020
TI  - Interaction of Mg2+ with the allosteric site of muscarinic M2 receptors.
AB  - Mg2+-ions have been suspected to attenuate the inhibitory effect of allosteric
      modulators on the dissociation of orthosteric ligands from muscarinic M2
      receptors. It was aimed to gain more insight into the molecular events underlying
      the effect of Mg2+. The interaction of Mg2+ with the allosteric model compounds
      W84 (hexane-1,6-bis [dimethyl-3'-phthalimidopropylammonium bromide]) and Chin3/6
      (hexane-1 ,6-bis[dimethyl-3'-?4-oxo-2-phenyl-3,4-dihydro-2H-quinazolin-1-yl
      propylammonium bromide]) was studied in porcine heart muscarinic receptors, the
      primary binding site of which was occupied by the ligand [3H]N-methylscopolamine
      ([3H]NMS). The incubation buffer was composed of 4 mM Na2HPO4 and 1 mM KH2PO4 (pH
      7.4, 23 degrees C). The retardation of [3H]NMS dissociation (control t1/2=5.6
      min) induced by the allosteric test compounds was diminished by 3 mM Mg2+ to a
      greater extent than to be expected with regard to its contribution to the ionic
      strength of the buffer solution. Concentration-effect curves for the allosteric
      retardation of [3H]NMS dissociation by W84 (half maximal effective concentration
      EC0.5=24 nM in the absence of Mg2+) and by Chin3/6 (EC0.5=28 nM) were shifted by
      Mg2+ to the right in a parallel fashion. The curve-shift was compatible with a
      competitive interplay between Mg2+ and the modulators. The pKb-values as a
      measure of the antagonistic potency of Mg2+, however, differed depending on the
      modulator, i.e. pKb=3.4 with W84 and pKb=2.8 with Chin3/6. Mg2+ itself was
      capable of slowing the dissociation of [3H]NMS; the maximal retardation of
      [3H]NMS dissociation was about 3 fold, the concentration-effect relationship was
      compatible with a two-site model using the above-mentioned pKb-values as affinity
      constants. Since the equilibrium-binding of [3H]NMS remained unchanged up to a
      Mg2+-concentration of 3 mM, the cation appears to inhibit the association and
      dissociation of [3H]NMS to the same extent in this concentration range. Taken
      together, the findings indicate that Mg2+ may bind to the allosteric region of
      muscarinic M2 receptors and that more than one site is involved in this
      interaction. The sites of action may represent divalent cation binding sites.

PMID- 9606021
TI  - Effects of phosducin on the GTPase cycle of Go.
AB  - The cytosolic phosphoprotein phosducin is an inhibitor of G-protein GTPase
      activity and G-protein-mediated signalling. Here we investigate the effects of
      phosducin on individual steps of the GTPase cycle of Go, and the role of the G
      protein betagamma subunits in mediating these effects. Phosducin was expressed in
      E. coli and purified to apparent homogeneity. Phosducin inhibited the MAS-7
      stimulated as well as basal steady-state GTPase activity of Go, but did not
      affect the GTP-hydrolytic step. It slowed the release of GDP from Go in the
      presence of high Mg2+ concentrations (25 mM), and enhanced GDP release at low
      Mg2+ concentrations (100 microM). Likewise, phosducin inhibited basal GTPase
      activity at 25 mM Mg2+ and stimulated at 100 microM Mg2+. All of these effects
      were lost following phosphorylation of phosducin by protein kinase A (PKA). These
      observations are compatible with the hypothesis that phosducin antagonizes the
      influence of betagamma subunits on alpha(o). Titration of the effects of
      phosducin on the GDP release and GTPase activity of Go and on the betagamma
      subunit-dependent ADP-ribosylation of alpha(o) by pertussis toxin indicated an
      apparent affinity of approximately 20 nM. We conclude that via high-affinity
      interactions with G-protein betagamma subunits phosducin decreases the proportion
      of active GTP-bound G-proteins by slowing GDP-release without affecting GTP
      hydrolysis, and that thereby it inhibits G-protein-mediated signalling.

PMID- 9606022
TI  - Activation of a Ca2+-dependent K+ current by the oncogenic receptor protein
      tyrosine kinase v-Fms in mouse fibroblasts.
AB  - We investigated the effects of the receptor-coupled protein tyrosine kinase (RTK)
      v-Fms on the membrane current properties of NIH3T3 mouse fibroblasts. We found
      that v-Fms, the oncogenic variant of the macrophage colony-stimulating factor
      receptor c-Fms, activates a K+ current that is absent in control cells. The
      activation of the K+ current was Ca2+-dependent, voltage-independent, and was
      completely blocked by the K+ channel blockers charybdotoxin, margatoxin and
      iberiotoxin with IC50 values of 3 nM, 18 nM and 76 nM, respectively. To identify
      signalling components that mediate the activation of this K+ current, NIH3T3
      cells that express different mutants of the wild-type v-Fms receptor were
      examined. Mutation of the binding site for the Ras-GTPase-activating protein led
      to a complete abolishment of the K+ current. A reduction of 76% and 63%,
      respectively, was observed upon mutation of either of the two binding sites for
      the growth factor receptor binding protein 2. Mutation of the ATP binding lobe,
      which disrupts the protein tyrosine kinase activity of v-Fms, led to a 55%
      reduction of the K+ current. Treatment of wild-type v-Fms cells with Clostiridium
      sordellii lethal toxin or a farnesyl protein transferase inhibitor, both known to
      inhibit the biological function of Ras, reduced the K+ current amplitude to 17%
      and 6% of the control value, respectively. This is the first report showing that
      an oncogenic RTK can modulate K+ channel activity. Our results indicate that this
      effect is dependent on the binding of certain Ras-regulating proteins to the v
      Fms receptor and is not abolished by disruption of its intrinsic protein tyrosine
      kinase activity. Furthermore, our data suggest that Ras plays a key role for K+
      channel activation by the oncogenic RTK v-Fms.

PMID- 9606023
TI  - Inhibition of insulin-stimulated glucose transport in 3T3-L1 cells by Clostridium
      difficile toxin B, Clostridium sordellii lethal toxin, and Clostridium botulinum
      C2 toxin.
AB  - The role of the actin cytoskeleton and/or GTPases of the Rho/Rac-family in
      glucose transport regulation was investigated in 3T3-L1 cells with clostridial
      toxins which depolymerize actin by inactivation of Rho/Rac (Clostridium difficile
      toxin B and Clostiridium sordellii lethal toxin (LT)) or by direct ADP
      ribosylation (Clostridium botulinum C2 toxin). Toxin B and C2 reduced insulin
      stimulated, but not basal, 2-deoxyglucose (2-DOG) uptake rates in 3T3-L1
      fibroblasts. In parallel, the toxins produced morphological alterations of the
      cells reflecting disruption of the actin cytoskeleton. Both toxins reduced the
      maximum response to insulin but failed to alter the half-maximally stimulating
      concentrations of insulin. In 3T3-L1 adipocytes, the lethal toxin reduced the
      effect of insulin on 2-DOG uptake, whereas toxin B and C2 failed to affect
      glucose transport or cell morphology. When cells were exposed to the toxins after
      treatment with insulin, both toxin B and the lethal toxin, in contrast to the
      phosphatidylinositol (PI) 3-kinase inhibitor wortmannin, failed to reduce the 2
      DOG uptake rates. Thus, both translocation to the plasma membrane and
      internalization of glucose transporters were inhibited by the toxins, whereas the
      PI 3-kinase inhibitor selectively affects translocation. The data suggest that
      the effects of the clostridial toxins on trafficking of glucose transporters are
      mediated by the depolymerization of the actin cytoskeleton and are an indirect
      consequence of Rho or Rac inactivation. It is suggested that pathways signalling
      through Rac or Rho may play a modulatory role in glucose transport regulation
      through their effects on the actin network.

PMID- 9606024
TI  - Characterization of 5-ht6 receptor and expression of 5-ht6 mRNA in the rat brain
      during ontogenetic development.
AB  - We have determined the pharmacological characteristics of the rat 5-ht6 receptor
      stably expressed in CHO cells. Moreover, using RT-PCR experiments the in vivo
      expression of the gene encoding this receptor was studied in rat at various
      embryonic days (ED) starting from ED10 to birth (PN0) and at post-natal days (PN)
      up to PN36. The pharmacological analysis of the [3H]5-HT binding in stably
      transfected CHO cells expressing rat 5-ht6 receptors revealed the presence of a
      single class of high affinity saturable binding sites for 5-HT corresponding to
      an affinity constant: Kd=27.2+/-3.4 nM. This receptor also exhibited a high
      affinity for a number of typical and atypical antipsychotics, tricyclic
      antidepressant drugs and ergot alkaloids. In stably transfected CHO cells,
      serotonin elicited a potent stimulation of adenylyl cyclase activity which was
      blocked by antipsychotic and antidepressant drugs. These results confirm the
      hypothesis that 5-ht6 receptors may correspond to an important target for
      atypical antipsychotics and reveal an original pharmacological profile for this
      receptor. The study of the ontogeny of the 5-ht6 mRNA in rat developing brain
      showed that 5-ht6 mRNA were first detectable with a high level on ED12, slighly
      decreased up to ED17 and then remained stable at high level until the adult age.
      The ontogenetic pattern of 5-ht6 mRNA expression appeared to correlate with the
      occurence of the first cell bodies of serotonergic neurons; the early expression
      of 5-ht6 mRNA and the fact that this receptor is positively coupled to the
      production of cAMP may suggest a role for 5-ht6 receptor in the early growth
      process involving the serotonergic system.

PMID- 9606025
TI  - Neurosteroids may differentially affect the function of two native GABA(A)
      receptor subtypes in the rat brain.
AB  - Hippocampal noradrenergic and cerebellar glutamatergic axon terminals are known
      to possess GABA(A) receptors mediating, respectively, enhancement of
      noradrenaline (NA) and glutamate release. It has been recently found that the
      hippocampal receptor is benzodiazepine-sensitive, whereas the cerebellar receptor
      is insensitive to benzodiazepine agonists. We here tested the effects of
      neurosteroids on these two native GABA(A) receptors using superfused rat
      hippocampal and cerebellar synaptosomes. Allopregnanolone (3alpha,5alpha-P), at
      nanomolar concentrations, potentiated the GABA-induced [3H]-NA release from
      superfused hippocampal synaptosomes; in the absence of GABA, the steroid was
      ineffective up to 10 microM. The enhancement by GABA of the K+-evoked [3H]-D
      aspartate release from cerebellar synaptosomes also was potentiated by nanomolar
      3alpha,5alpha-P; in addition, at 1-10 microM, the steroid increased [3H]-D
      aspartate release in the absence of GABA. Both in hippocampus and cerebellum the
      potentiations of the GABA effects produced by nanomolar 3alpha,5alpha-P were
      abolished by dehydroepiandrosterone sulphate (DHEAS). Added up to 10 microM,
      DHEAS could not inhibit the effects of GABA alone. The enhancement of [3H]-D
      aspartate release elicited by 3 microM 3alpha,5alpha-P in the absence of added
      GABA was antagonized completely by bicuculline and picrotoxin and halved by
      DHEAS. To conclude, 3alpha,5alpha-P, at nanomolar concentrations, behaves as a
      positive allosteric GABA modulator at both the GABA(A) receptors under study. Low
      micromolar 3alpha,5alpha-P can directly activate the cerebellar receptor, whereas
      the hippocampal GABA(A) receptor is insensitive to the neurosteroid alone. DHEAS
      appears to be a pure antagonist at the neurosteroid allosteric sites. Along with
      the previously observed differential sensitivity to benzodiazepines, the present
      data strengthen the idea that the two receptors investigated represent native
      subtypes of the GABA(A) receptor having distinct pharmacology, neuronal
      localization and function.

PMID- 9606027
TI  - U-83836E prevents kainic acid-induced neuronal damage.
AB  - The effect of kainic acid (KA) on mitochondrial membrane potential (MMP) and
      reactive-oxygen species (ROS) production was studied in dissociated cerebellar
      granule cells from rat pups. KA induced a maximum increase of 361%+/-35% in ROS
      production. The lazaroid compound U-83836E (at concentrations ranging from 10(-9)
      to 5x10(-6) M) completely inhibited this increase, with an IC50 value of 3.02+/
      1.08x10(-7) M. KA also decreased the mitochondrial membrane potential (MMP), with
      a maximum decrease of about 30%. Absence of Na+ in the incubation medium did not
      significantly alter the effect of KA on MMP. As expected, the AMPA/kainate
      receptor antagonist NBQX inhibited the effects of KA on MMP with an IC50 value of
      1.1+/-0.8 microM. However, the lazaroid U-83836E, indomethacin, nor
      dihydroguaiaretic acid and L-nitroarginine all failed to inhibit the KA-induced
      decrease in the MMP. Finally, to assess the neuroprotective effect of U-83836E on
      KA-induced neurotoxicity in vivo, the increase in the peripheral-type
      benzodiazepine receptor density in rat hippocampus was measured. Treatment with
      KA increased the Bmax to 1341+/-192 fmol mg(-1). When U-83836E was coadministered
      with KA, the Bmax was reduced to 765+/-122 fmol mg(-1), which was not
      significantly different from the Bmax obtained from untreated rats (Bmax: 518+/
      33 fmol mg(-1)). We conclude that treatment with the lazaroid U-83836E might be a
      suitable therapeutic strategy in neurodegenerative disorders.

PMID- 9606026
TI  - Differential effects of phosphonic analogues of GABA on GABA(B) autoreceptors in
      rat neocortical slices.
AB  - The effects of five phosphonic derivatives of GABA on the release of [3H]-GABA
      from rat neocortical slices, preloaded with [3H]-GABA, were investigated.
      Phaclofen and 4-aminobutylphosphonic acid (4-ABPA) increased the overflow of [3H]
      evoked by electrical stimulation (2 Hz) in a concentration-dependent manner, with
      similar potencies (phaclofen EC50=0.3 mmol/l, 4-ABPA EC50=0.4 mmol/l). At 3
      mmol/l, phaclofen increased the release of [3H]-GABA by 82.6+/-8.6%, and 4-ABPA
      increased the release by 81.3+/-9.0%. 2-Amino-ethylphosphonic acid (2-AEPA)
      increased the overflow of [3H] by 46.8+/-10.9% at the highest concentration
      tested (3 mmol/l). In contrast, the lower phosphonic homologue 3
      aminopropylphosphonic acid (3-APPA), and 2-amino-2-(p-chlorophenyl)
      ethylphosphonic acid (2-CPEPA), a baclofen analogue, did not modify the
      stimulated overflow. These results suggest that phaclofen, 4-ABPA and 2-AEPA are
      antagonists at GABA(B) autoreceptors, the latter being the weakest antagonist,
      whilst neither 3-APPA nor 2-CPEPA are active at these receptors. Since phaclofen,
      4-ABPA and 2-CPEPA are antagonists and 3-APPA a partial agonist/antagonist on
      GABA(B) heteroreceptors, the lack of effect of 3-APPA and 2-CPEPA on [3H]-GABA
      release in this study suggests that GABA(B) autoreceptors may be
      pharmacologically distinct from the heteroreceptors.

PMID- 9606028
TI  - Pharmacological modulation of the refractory period of retinal spreading
      depression.
AB  - Spreading depression (SD) is a propagating wave of neuronal activity in the
      central nervous system and may play a role in triggering classical migraine. The
      retina serves as a model system for examining the phenomenon of SD and the
      influence of various drugs on it. After a SD wave passes a new wave can not be
      elicited in the absolute refractory period of the tissue (about 2 min), this is
      followed by a relative refractory phase of about 20 min before complete recovery.
      The aim of the present study was to describe the effects of Ba2+, a blocker of
      glial cell K+ channels, octanol, a gap junction blocker and diethylbarbiturate, a
      GABA(A) chloride channel-activating drug on the modulation of the refractory
      period of the retinal SD and to examine the possible mechanisms underlying this
      modulation. Two properties of SD, which are highly sensitive to any changes in
      the experimental conditions, are the propagation velocity of the wave and the
      accompanying slow negative potential shift. We measured the propagation velocity
      and the field potential amplitude in the chicken retina as a function of the
      recovery state of the tissue under control conditions and compared them with
      measurements in the presence of Ba2+, octanol or diethylbarbiturate. Under these
      conditions the manner of the recovery of the tissue changed significantly.
      Although after blocking the glial (Muller) cell K+ channels with Ba2+ (200
      microM), the curve of recovery of the propagation velocity to its maximum value
      has the same shape as under control conditions, the propagation velocity is
      reduced in the whole recovery period and in the recovered retina to 84% of the
      control velocity. The importance of electrical coupling in the refractory phase
      and in the recovered tissue was examined by adding octanol (1 mM) to the
      perfusion solution. In this case the relative recovery phase was shortened and
      the field potential amplitude (110% of control) and propagation velocity (112% of
      control) are increased in the completely recovered retina. With the GABA(A)
      chloride channel-activating drug diethylbarbiturate (800 microM) the propagation
      velocity (112% of control) and the amplitude of the field potential (111% of
      control) in the complete recovered retina are increased, but this seems to have
      no influence on the refractory state.

PMID- 9606029
TI  - Central activation of the sympathetic nervous system including the adrenals in
      anaesthetized guinea pigs by the muscarinic agonist talsaclidine.
AB  - Talsaclidine, a novel M1-receptor selective muscarinic agonist for cholinergic
      substitution therapy of Alzheimer's disease, activates the sympathetic nervous
      system in guinea pigs and dogs at the orthosympathic ganglia and the
      paraganglionic adrenals. Results from guinea pigs provide indirect evidence for
      an additional central site of action. The present investigation in anaesthetized
      and vagotomized guinea pigs intended to demonstrate central activation of the
      sympathetic nervous system directly by comparing the blood pressure effects of
      intracerebroventricular and intravenous injections of small doses of
      talsaclidine. Increasing doses of 0.2 and 0.6 mg/kg talsaclidine were injected
      alternately into the third cerebral ventricle and intravenously in 6 guinea pigs
      before and after blockade of peripheral muscarinic receptors with 1 mg/kg
      ipratropium bromide i.v. In another group of 6 animals the injections were given
      into the cisterna cerebellomedullaris using the same protocol. In both groups
      central administration of talsaclidine caused dose-related hypertension while
      intravenous injections were hypotensive. Ipratropium bromide, a peripheral
      antimuscarinic drug, reversed this hypotensive action of intravenous talsaclidine
      into hypertension, but did not inhibit the effects of central administration. In
      contrast, atropine, an antimuscarinic drug which passes the blood-brain barrier,
      abolished the effect of 0.6 mg/kg talsaclidine injected into the cisterna
      cerebellomedullaris of 8 guinea pigs. The hypertensive effect of a first
      injection of 0.6 mg/kg talsaclidine into the cisterna cerebellomedullaris of 6
      guinea pigs was approximately twice as large as that of a second given 90 min
      after bilateral adrenalectomy. Sham operation in another 6 animals was not
      inhibitory. The results demonstrate that talsaclidine, a selective muscarinic M1
      receptor agonist, activates central parts of the sympathetic nervous system,
      including central projections of the adrenals by an action mediated by central
      muscarinic receptors.

PMID- 9606030
TI  - P2-receptor-mediated inhibition of noradrenaline release in the rat pancreas.
AB  - The aim of the study was to find out whether, and if so through which receptors,
      nucleotides modulate the release of noradrenaline in the rat pancreas. Segments
      of the pancreas were preincubated with [3H]-noradrenaline, superfused with medium
      containing desipramine (1 microM) and yohimbine (1 microM), and stimulated
      electrically, in most experiments by 60 pulses/l Hz. The adenosine A1-receptor
      agonist N6-cyclopentyl-adenosine (CPA; EC50 32 nM), the non-subtype-selective
      adenosine receptor agonists adenosine (EC50 15 microM) and 5'-N
      ethylcarboxamidoadenosine (NECA; EC50 135 nM), and the nucleotides ATP (EC50 13
      microM), adenosine-5'-O-(3-thiotriphosphate) (ATPgammaS; EC50 19 microM) and
      adenosine-5'-O-(2-thiodiphosphate) (ADPbetaS; EC50 16 microM) decreased the
      evoked overflow of tritium. The adenosine A2A-agonist 2-p-(2-carboxyethyl)
      phenethylamino-5 '-N-ethylcarboxamido-adenosine (CGS 21680) caused no change. The
      concentration-response curve of CPA was shifted to the right by the A -antagonist
      8-cyclopentyl-1,3-dipropylxanthine (DPCPX 10 nM; pKd 9.1) but, like the
      concentration-response curve of adenosine, hardly affected by the P2-receptor
      antagonist cibacron blue 3GA (30 microM). Combined administration of a high
      concentration of DPCPX (1 microM) and 8-phenyltheophylline (10 microM) abolished
      the effects of CPA and NECA. The concentration-response curves of ATP and
      ADPbetaS were shifted to the right by both DPCPX (10 nM; pKd 8.7 and 8.9,
      respectively) and cibacron blue 3GA (30 microM; pKd 5.0 and 5.2, respectively).
      The antagonist effects of DPCPX (10 nM) and cibacron blue 3GA (30 microM) against
      ATP were additive in a manner compatible with the blockade of two separate
      receptors for ATP. In the presence of the high concentration of DPCPX (1 microM)
      and 8-phenyltheophylline (10 microM), ATP and ADPbetaS still decreased evoked
      tritium overflow, and this decrease was attenuated by additional administration
      of cibacron blue 3GA (30 microM). The P2-antagonists cibacron blue 3GA, reactive
      blue 2, reactive red 2, and to a limited extent also suramin and 8-(3,5-dinitro
      phenylenecarbonylimino)- 1,3,5-naphthalenetrisulphonate (XAMR0721), increased the
      evoked overflow of tritium by up to 114%. Pyridoxalphosphate-6-azophenyl-2',4'
      disulphonate (PPADS) caused no change. The results indicate that the
      postganglionic sympathetic axons of the rat pancreas possess A1-adenosine and P2
      receptors. Both receptors mediate an inhibition of noradrenaline release. The
      presynaptic P2-receptors are activated by an endogenous ligand, presumably ATP,
      during appropriate trains of action potentials. This is the first demonstration
      of presynaptic P2-receptors at postganglionic sympathetic neurons that are
      located in prevertebral ganglia.

PMID- 9606031
TI  - Blockade of voltage-operated calcium channels, increase in spontaneous
      catecholamine release and elevation of intracellular calcium levels in bovine
      chromaffin cells by the plant alkaloid tetrandrine.
AB  - Experiments were performed in bovine chromaffin cells in short term primary
      culture. Tetrandrine is a plant alkaloid from the chinese medical herb Stefania
      tetrandra. The aim of the present study was to investigate the mechanisms by
      which tetrandrine interacts with calcium signalling and to provide a quantitative
      description of effects. Tetrandrine blocked voltage-operated calcium channel
      currents concentration-dependently as shown in whole cell patch-clamp recordings.
      The blockade of calcium channels reduced the potassium-stimulated catecholamine
      release. Besides, the drug increased the spontaneous (not stimulated) release of
      catecholamines in the presence of extracellular calcium. Measurements of
      intracellular calcium levels [Ca]i showed a calcium release from intracellular
      stores by tetrandrine. This tetrandrine-induced [Ca]i elevation was higher in
      calcium containing as compared to calcium free solution. Tetrandrine effects
      partially overlap with those of thapsigargin, but tetrandrine has additional
      targets, since it increased [Ca]i in cells pretreated with thapsigargin. We
      conclude that tetrandrine blocks voltage-operated calcium channels and increases
      [Ca]i by blocking endoplasmic and other calcium pumps.

PMID- 9606032
TI  - Relaxant effect of the calcitonin gene-related peptide (CGRP) on the nonpregnant
      and pregnant rat uterus. Comparison with vascular tissue.
AB  - To explore the role of calcitonin gene-related peptide (CGRP) in rat pregnancy,
      we determined the density of myometrial CGRP-encoded nerve fibre terminals and
      examined, in an organ bath, the relaxant effect of the peptide on uterine strips
      near parturition. Comparisons were made with the uterus and aorta of nonpregnant
      rats. In the myometrium, CGRP immunoreactive nerve fibers were abundant in
      nonpregnant rats and scarce at the parturient stage. In the aorta there was no
      variation in the density of CGRP fibres with gestation. In nonpregnant rats only,
      CGRP relaxed spontaneous and tetrodotoxin (TTX)-sensitive electrically-evoked
      uterine contractions (EC50 40 nM, Emax 80%). The effect was antagonized by CGRP[8
      37] (pKB 6.47) but was not affected by either blockers of nitricoxid synthase or
      ATP-sensitive potassium channels. CGRP was also able to relax contractions evoked
      by direct depolarization of the cells (TTX-insensitive contractions) (EC50, 2 nM,
      Emax 70%). In aorta contracted with arginine vasopressin, CGRP-induced relaxation
      was the same in nonpregnant and parturient animals. It was antagonized by CGRP [8
      371 (pKB 6.90) and was abolished in presence of the nitric oxide synthase
      inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME). Amylin neither relaxed
      the uterus nor the aorta. In pregnant rats, the relaxant effect of CGRP on the
      uterus was limited on day 21 and was totally absent on day 22 of gestation. We
      conclude that the primary relaxant effect of CGRP on the uterus occurs at the
      level of myometrial smooth muscle cells. In the myometrium, gestation decreases
      CGRP innervation and impairs the relaxant responses to CGRP. Such changes are not
      observed in vascular tissues like aorta.

PMID- 9606034
TI  - Chronic treatment with haloperidol diminishes the phencyclidine-induced
      sensorimotor gating deficit in rats.
AB  - Prepulse inhibition is a model in which a weak subthreshold stimulus (prepulse),
      presented to an individual before a strong stimulus (pulse), inhibits a startle
      response to the latter. A deficit of prepulse inhibition induced by
      dopaminomimetics and antagonists of NMDA receptors has been suggested as an
      animal model of the sensorimotor deficit in schizophrenia. The aim of the present
      study was to examine the effect of chronic treatment with the classic neuroleptic
      haloperidol on the disruption of prepulse inhibition induced by the uncompetitive
      antagonist of NMDA receptors phencyclidine (PCP, 5 mg/kg sc). Haloperidol in a
      dose of 1 mg/kg/day was given to rats in drinking water for 3 months. The PCP
      induced reduction in prepulse inhibition was not reversed by short-term (4-day)
      haloperidol administration. In contrast, long-term treatment with haloperidol (6
      weeks or 3 months) diminished the PCP-induced effect. The present study suggests
      that the improvement in sensorimotor gating in the PCP model in rats by prolonged
      treatment with haloperidol may reflect its antipsychotic action.

PMID- 9606033
TI  - The influence of post-mortem conditions on contractile and relaxant
      responsiveness of guinea-pig isolated tracheal smooth muscle.
AB  - Responsiveness to various contractile and relaxant agonists was assessed in
      tracheal preparations from guinea-pigs that had been incubated in situ at 4-37
      degrees C for 0-168 h post-mortem. The potencies of histamine and acetylcholine
      were increased up to 168 h at 4 degrees C post-mortem and up to 24 h post-mortem
      at 22 degrees C. Histamine potency also increased with increasing post-mortem
      time at 37 degrees C. After 48 h at 22 degrees C and 8 h at 37 degrees C,
      responses to all spasmogens were abolished. Increases in histamine and
      acetylcholine potencies were similarly observed in tracheal tissue that had been
      removed at death and then incubated at 4 degrees C in oxygenated Krebs
      bicarbonate solution for 0-168 h. The increased potency of these drugs may be
      explained by epithelial damage and/or loss of an epithelium-derived inhibitory
      factor (EpDIF). Both basal and spasmogen-stimulated increases in intracellular
      phosphoinositides fell with increasing time and ambient temperature post-mortem,
      despite the fact that contraction in response to these agonists could still be
      evoked. This suggests the selective failure of this signal transduction pathway
      and the maintenance of responsiveness via other mechanisms. The potencies and
      maximum effects of relaxant agonists remained unaltered in tracheal tissue with
      increasing time post-mortem, suggesting little change in the function of the
      appropriate receptor-signal transduction processes. This study has therefore
      demonstrated that at 4 degrees C. contractile and relaxant responses were
      preserved for up to 168 h post-mortem, although the modulatory influence of the
      epithelium on histamine and acetylcholine responses was rapidly lost.

PMID- 9606036
TI  - Evidence for morphine-induced galactorrhea in male cynomolgus monkeys.
AB  - We evaluated the effect of a daily injection of morphine hydrochloride on
      galactorrhea in male cynomolgus monkeys. Three groups of three monkeys (nine
      total) were used. The treatment schedule was separated into three periods: pre
      treatment, treatment, and post-treatment. Each group of monkeys was
      subcutaneously injected daily with 1.5, 3.0, or 6.0 mg/kg (monkey weight) of
      morphine for 74-130 days, respectively, during the treatment period, and with
      saline during the pre-treatment and post-treatment periods. We then measured the
      prolactin (PRL) and testosterone (T) levels from weekly blood samples that were
      taken 20 hours after injection. No statistically significant differences in
      either the PRL or T level were detected throughout the treatment period. However,
      monkeys treated with 3.0 and 6.0 mg/kg/day showed a decrease in T level and an
      increase in PRL level during the early post-treatment period. Seven of the nine
      monkeys produced a milk-like secretion from their mammary gland (a symptom of
      galactorrhea) during the treatment and post-treatment periods. For several months
      of post-treatment period (average 6.75 months), we monitored the time-course
      changes in PRL and T levels in all monkeys for 10 hours after a single injection
      of morphine at the same dose given during the treatment period. Morphine induced
      a sudden increase in the PRL level (peaked within 30 minutes) and a gradual
      decrease in the T level (leveled off within 6.5-10 hours), and then returned to
      basal levels. These results indicate that morphine does not cause a long-term
      effect on hormonal changes and that a morphine-induced transient rise in PRL
      levels accompanied by a decrease in T levels can induce spontaneous galactorrhea
      in male cynomolgus monkeys.

PMID- 9606035
TI  - Acetylcholine and nicotine stimulate the release of granulocyte-macrophage colony
      stimulating factor from cultured human bronchial epithelial cells.
AB  - Primary cultures of human bronchial epithelial cells (HBE-cells) were established
      to measure granulocyte-macrophage colony stimulating factor (GM-CSF) release. HBE
      cells showed a basal GM-CSF release (82+/-20 ng/well/24 h; 30 donors), which was
      increased by interleukin-1 beta(IL-1beta, 1 ng/ml) by 270%. This effect was
      blocked by 1 microM dactinomycin or 10 microM cycloheximide, i.e. the stimulatory
      effect of IL-1beta depended on de-novo synthesis. Histamine (100 microM) and
      acetylcholine ( 100 nM) stimulated GM-CSF release more than two-fold above the
      baseline. Nicotine (1 microM) increased GM-CSF release to a similar extent, and
      this effect was prevented by 30 microM (+)-tubocurarine. The stimulatory effect
      was attenuated or even lost with high agonist concentrations (10 microM
      acetylcholine; 100 microM nicotine) suggesting receptor desensitization. The
      muscarinic receptor agonist oxotremorine did not affect GM-CSF release.
      Serotonin, substance P and calcitonin-gene related peptide had no effect on GM
      CSF release. In conclusion, acetylcholine can trigger GM-CSF release from human
      airway epithelial cells via stimulation of nicotinic receptors.

PMID- 9606037
TI  - Localization of testosterone and 3beta-hydroxysteroid dehydrogenase/delta5-delta4
      isomerase in cynomolgus monkey (Macaca fascicularis) testes.
AB  - The enzyme 3beta-hydroxysteroid dehydrogenase/delta5-delta4-isomerase (3beta-HSD)
      is essential for the biosynthesis of all classes of steroid hormones, including
      androgens. We localized testosterone and 3beta-HSD by light microscopic
      immunocytochemistry in the testes of adult cynomolgus monkeys. Immunoreactive
      testosterone was located as intense deposits in the labeled cytoplasm of Leydig
      cells, and located weakly in the interstitial tissues, basement membranes, and
      the regions near tubular walls within tubules. Immunoreactive 3beta-HSD was
      located in the cytoplasm of all Sertoli cells and was especially intense in the
      parts near tubular walls and located weakly to intensely in the cytoplasm of some
      Leydig cells. This is the first immunocytochemical evidence that Sertoli cells of
      cynomolgus monkeys, as well as Leydig cells, are involved in biosynthesis of
      androgens.

PMID- 9606039
TI  - Chimpanzee lipoprotein(A): Relationship between apolipoprotein(A) isoform size
      and the density profile of lipoprotein(A) in animals with different heterozygous
      apo(A) phenotypes.
AB  - In a previous study [C. Doucet et al., J. Lipid Res 35:263-270, 1994], we have
      shown that plasma lipoprotein (a) [Lp(a)] levels were significantly elevated in a
      population of unrelated chimpanzees as compared to those in normolipidemic human
      subjects. Nonetheless, the inverse correlation between Lp(a) levels and
      apolipoprotein (a) [apo(a)] isoforms typical of man was maintained in the
      chimpanzee. In the present study, we describe the density profiles of apo B- and
      apo A1-containing lipoproteins and of Lp(a) in chimpanzee plasmas heterozygous
      for apo(a) isoforms after fractionation by single spin ultracentrifugation in an
      isopycnic gradient. The distribution of apo(a) isoforms in the density gradient
      was also examined by SDS-agarose gel electrophoresis and immunoblotting using
      chemiluminescence detection. In all double-band phenotypes examined, the smallest
      isoform was present along the entire length of the density gradient. The density
      distribution of the second isoform varied according to the size difference
      between the respective isoforms. Two isoforms close in size (difference in
      apparent molecular mass = 60 kDa) were present together in every gradient
      subfraction. On the contrary, when the two isoforms displayed distinct molecular
      mass (maximal difference in apparent molecular mass = 340 kDa), then the largest
      was principally present in the densest fractions of the gradient (d > 1.1 mg/ml).
      These observations suggest that Lp(a) particles with small apo(a) isoforms are
      more susceptible to interact with other lipoproteins than are Lp(a) particles
      with large isoforms.

PMID- 9606038
TI  - Reproductive exocrine and endocrine profiles and their seasonality in male langur
      monkeys (Presbytis entellus entellus).
AB  - The reproductive exocrine and endocrine profiles in male langurs are reported
      with an emphasis on seasonality. The animals showed positive response to
      electroejaculation throughout the year. The sperm concentration varied between 10
      383 x 10(6)/ejaculation with wide fluctuations all through the year. No
      appreciable changes in the motility and percent live sperm were observed
      throughout the year. The levels of seminal fructose and magnesium remained
      unchanged throughout the year, while acid phosphatase showed wide fluctuations.
      Citric acid showed elevation during February and March and LDH showed elevated
      levels during April and May. The annual range of serum testosterone was 6-34
      nMol/l with a peak during July. Cortisol ranged between 575-1587 nMol/l and
      prolactin ranged between 107-900 mU/l. Wide fluctuations were observed in
      hormonal levels. No seasonality was exhibited in the seminiferous tubule
      diameter, nuclear diameter of Sertoli cells and Leydig cells, and the
      cholesterol, glycogen, and sialic acid contents of testis. None of the parameters
      studied have shown any correlation with season. The results suggest that the male
      langurs lack seasonality in their reproductive exocrine and endocrine profiles
      and thus could be used as model for research in human reproduction.

PMID- 9606040
TI  - Estimation of gestational ages in the common marmoset (Callithrix jacchus) from
      published prenatal growth curves.
AB  - This report compares estimated gestational ages from published cubic spline
      curves to gestational ages estimated retrospectively from delivery dates in 28
      pregnancies from ten common marmosets (Callithrix jacchus). Both CRL- and BPD
      based estimates of gestational age were closely correlated with delivery-based
      gestational age estimates. Of the three ultrasound machines used, the one with 16
      shades of gray and a sequential linear array overestimated gestational age during
      early pregnancy, based on CRL measures. Measures from the other two machines (64
      or 264 shades of gray; linear sector and annular array or electronic phase array)
      were similar and resulted in a correlation of the two estimates of gestational
      age of 0.94 and a mean difference between the two estimates of 0.16 days with 80%
      of CRL-based gestational age estimates being within +/- 5 days of the delivery
      based estimate. The reliability of BPD-based estimates of gestational age was
      strongly related to pregnancy outcome. BPD-based estimates underestimated
      gestational age in poor outcome pregnancies (i.e., those in which infants died
      within 7 days of birth) but not in good outcome pregnancies. The combined CRL-
      and BPD-based estimates on poor outcome pregnancies suggest that there was less
      growth in BPD in late gestation for those pregnancies that resulted in nonviable
      offspring. For good outcome pregnancies, the correlation between BPD-based and
      delivery-based estimates of gestational age was 0.871 and the mean difference
      between the two estimates was -0.06 days with 83.3% of BPD-based estimates
      falling within +/- 5 days of delivery-based estimates.

PMID- 9606042
TI  - Secnidazole vs. paromomycin: comparative antiprotozoan treatment in captive
      primates.
AB  - The antiprotozoan activity of secnidazole was studied in Cercocebus t. torquatus,
      Cercopithecus campbelli, Erythrocebus patas (Cercopithecidae), and Gorilla
      gorilla (Pongidae) compared with that of paromomycin in Cercocebus t. lunulatus
      (Cercopithecidae), E. patas, and G. gorilla (Pongidae) by coprological analysis.
      The antiprotozoan activity of both drugs depended on the parasite species and the
      host species. The drugs acted in a similar way on Entamoeba coli parasitising C.
      t. torquatus, and E. patas. This activity was different from that observed on I.
      buestchlii from the same host species. Nevertheless, E. coli parasitising
      cercopithecids and pongids responded to drugs differently.

PMID- 9606041
TI  - Seroprevalence of specific viral infections in confiscated orangutans (Pongo
      pygmaeus).
AB  - A serological survey of confiscated orangutans was conducted to determine the
      prevalence of specific viral infections cross reacting with human viruses.
      Antibodies specific for human hepatitis A (HAV) and B (HBV) viruses, herpes
      simplex viruses (HSV), and human T-lymphotropic virus (HTLV types I and II), as
      well as for the simian type D retroviruses (SRV types 1 to 3) and simian
      immunodeficiency virus (SIV) were tested in samples from 143 orangutans. Results
      revealed a high prevalence of potential pathogens. The most prevalent viral
      infection found was HBV (59.4% prevalence) of which 89.4% of infected individuals
      seroconverted to the non-infectious state and 10.6% remained as chronic carriers.
      Antibodies to HAV, HSV, HTLV-1, and SRV were also detected but at a lower
      prevalence. There was no evidence of lentiviral infections in this group of
      animals. The results confirm the importance of quarantine and the need for
      diagnostic differentiation of virus infections to determine if they are of human
      origin or unique orangutan viruses.

PMID- 9606043
TI  - A method for creating reversible ureteric obstruction in the primate.
AB  - A technique has been developed for the establishment of a state of reversible,
      ureteric obstruction in the primate. Ten adult males had baseline 99mTc-DTPA
      renogram studies. A randomly selected ureter was totally occluded and obstruction
      confirmed on renogram. The occlusion was reversed and subsequent renograms
      confirmed recovery of activity in the obstructed kidneys of the eight animals who
      survived the reversal procedure. Seven were alive on conclusion of the study.
      Prevention of ureteric strictures was achieved with an intra-ureteric silastic
      tube. Autopsies demonstrated patency of every previously occluded ureter. This is
      the first study to be reported in primates, and the second overall, in which
      complete ureteric obstruction and its successful reversal has been confirmed on
      renogram using this surgical method. The technique is suitable for the study of
      the effect of reversible ureteric obstruction on renal function.

PMID- 9606044
TI  - A self calibration method using a soft clustering procedure for eye movement
      recordings.
AB  - A nearly automatic method for calibrating eye movement records has been
      developed. This very robust method is based on a soft clustering algorithm which
      allows exploration of the whole range of eye movement records for reliable
      calibration. In contrast to many other methods which carry out the calibration on
      several discrete points, this method is suitable for continuous determination of
      the transfer function of the eye movement transducer. Moreover it simultaneously
      uses the combined properties of vestibulo-ocular reflex, neck-to-eye reflex and
      smooth pursuit system to reach approximately a unity gain and zero phase lag (in
      subjects with no severe vestibular disorders or ocumomotor palsy). In addition,
      this method does not rely heavily on the degree of attention of the subject. The
      method is particularly suited for the calibration of non linear or noisy
      transducers like Electro Oculography (EOG). Calibration is performed within a few
      seconds. So when necessary in clinical applications it is possible to repeat
      calibrations frequently.

PMID- 9606045
TI  - A new slicing method for the lower vertebrate brain: brain mould and adjustable
      stage.
AB  - This paper describes a new method for slicing the lower vertebrate brain which is
      too small and soft to be sliced using conventional methods. The brain is sliced
      in a pre-prepared agar mould glued to a special stage placed in a conventional
      vibratome. The mould is constructed from a plaster model prepared by embedding a
      paraformaldehyde fixed brain in a paraffin and vaseline mixture. The brain to be
      sliced is placed within two prepared agar half cylinders which are in turn placed
      in a pre-prepared larger agar collar glued to a special stage. The study
      describes in detail the preparation of the interlocking collar and inner
      cylinders of agar. The plexiglass stage allows the agar block containing the
      brain, to be rotated and inclined to improve the angle of cut. By using this
      method, small and soft brain even with thin walls and large ventricles could be
      sliced coronally, sagittally, horizontally or obliquely. Brain slices obtained by
      this method have good viability showing spontaneous and evoked activity.

PMID- 9606046
TI  - Loss of CA1 cells following global ischaemia correlates with spatial deficits in
      the circular platform task.
AB  - The effect of 15 min, four-vessel-occlusion (4-VO) ischaemia on performance by
      rats in the circular platform task (CPT) was investigated. Possible correlations
      between the extent of hippocampal cell loss and behavioural disruption were
      evaluated. Sham-operated controls (n=10) and 4-VO ischaemic animals (n=32) were
      required to escape from a 1.2 m diameter, brightly illuminated, white surface
      into a dark goal box located under one of 18 equally-spaced, 9 cm diameter holes
      arranged around the circumference (3 trials per day). The goal box was maintained
      in a single, fixed, rewarded location relative to the extramaze cues for 7 days
      (days 16-22 post-ischaemia). During the reversal test, the goal box was
      transferred to a new location 140 degrees from the initial point and kept in this
      new position from day 23 through day 25 post-ischaemia. Ischaemic rats were
      slower to find the goal box than sham-operated controls; this learning deficit
      correlated with the degree of neuronal loss in the CA1, but not in the CA2, CA3
      and CA4 subfields and presubiculum of the hippocampal formation. During the
      reversal test, ischaemic rats persisted in searching for the goal box at the
      initially rewarded location. The circular platform task provides a good model for
      behavioural studies following transient forebrain ischaemia in the rat.

PMID- 9606047
TI  - Determination of stereotaxic coordinates for the hippocampus in the domestic pig.
AB  - In this study a stereotaxic instrument and a stereotaxic procedure based on
      external skull structures, to be used in prepubertal male Landrace pigs weighing
      less than 30 kg, is described. The instrument represents an adaptation of the
      apparatus designed by Marcilloux et al., Brain Res Bull 1989;22:591-597, but we
      have modified the instrument for stereotaxic procedures based on external skull
      structures, instead of intracerebral structures necessitating ventriculography
      (Marcilloux et al., Brain Res Bull 1989;22:591-597). For this reason the U-shaped
      frame and the ear-bar supports have been changed allowing the three-dimensional
      placement of the ear-bars into the oblique auditory canals. Firm fixation of the
      skulls of pigs weighing less than 30 kg, was furthermore secured with modified
      infraorbital ridges and hard palate pieces. Measurements of distances between
      external skull structures in animals of the same sex, age and weight showed a
      negligible variation, thus enabling definition of the horizontal, frontal and
      sagittal zero planes using external skull structures alone. Stereotaxic
      coordinates for the hippocampal region of male Landrace pigs weighing 10 kg were
      then provided and the coordinates from two different levels of the hippocampal
      region are presented in the text. The reliability of the stereotaxic instrument
      was finally secured by intrahippocampal injections of ink at predetermined
      coordinates.

PMID- 9606048
TI  - Small drug sample fabrication of controlled release polymers using the
      microextrusion method.
AB  - Ethylene vinylacetate polymer (EVA) has been used for many years to fabricate
      controlled-release polymeric implant devices with which drugs of high or low
      molecular weight compounds could be delivered with zero-order kinetics. However,
      because the known fabrication methods such as solvent evaporation, casting and
      possible shrinkage are not sufficiently controllable we have now developed the
      microextrusion method with which even small amount of clinically important and
      expensive drugs can be incorporated into EVA with high reproducibility. We show
      here that devices produced by the microextrusion method allows for a controlled
      delivery of several neurotoxic and neurotherapeutic compounds such as alpha
      methyl-p-tyrosine, diazepam, quinolinic acid, and phencyclidine. Each substance
      is slowly released from the polymer, as evidenced by spectrophotometric data, for
      up to 120 days at daily rates varying from 18.4 microg of phencyclidine to 97.6
      microg/day of diazepam. Thus, microextrusion is a valuable method for fabricating
      controlled-release polymers in which small amounts of scarce drugs can be
      incorporated. Another advantage of the current procedure is that polymers can be
      fabricated with very little amount of solvent.

PMID- 9606049
TI  - A computer-assisted test for the electrophysiological and psychophysical
      measurement of dynamic visual function based on motion contrast.
AB  - A new test is described that allows for electrophysiological and psychophysical
      measurement of visual function based on motion contrast. In a computer-generated
      random-dot display, completely camouflaged Landolt rings become visible only when
      dots within the target area are moved briefly while those of the background
      remain stationary. Thus, detection of contours and the location of the gap in the
      ring rely on motion contrast (form-from-motion) instead of luminance contrast. A
      standard version of this test has been used to assess visual performance in
      relation to age, in screening professional groups (truck drivers) and in clinical
      groups (glaucoma patients). Aside from this standard version, the computer
      program easily allows for various modifications. These include the option of a
      synchronizing trigger signal to allow for recording of time-locked motion-onset
      visual-evoked responses, the reversal of target and background motion, and the
      displacement of random-dot targets across stationary backgrounds. In all
      instances, task difficulty is manipulated by changing the percentage of moving
      dots within the target (or background). The present test offers a short,
      convenient method to probe dynamic visual functions relying on surprathreshold
      motion-contrast stimuli and complements other routine tests of form, contrast,
      depth, and color vision.

PMID- 9606050
TI  - Decomposing stimulus and response component waveforms in ERP.
AB  - Event-related potentials (ERPs) are evoked brain potentials that are averaged
      across many trial repetitions with individual trials aligned (i.e. time-locked)
      to a specific behavioral event, typically the onset of the stimulus (s-lock) or
      the onset of the behavioral response (r-lock). These evoked potential averages
      may reflect brain activities during the stimulus encoding/analyzing stage
      (stimulus component waveform, or 'S-component'), during the response
      preparation/production stage (response component waveform, or 'R-component'), or
      a combination thereof. In the stimulus-locked average of the ensemble of the
      recorded waveforms (i.e. in the s-locked ERP), the contribution of an R-component
      will be convoluted, due to the trial-by-trial variance in reaction time (RT): so
      will an S-component in the r-locked ERP. It is shown here that the knowledge of
      (1) the s-locked and r-locked ERP waveforms constructed from the same ensemble of
      trials and (2) the RT distribution of this ensemble allows us to determine
      whether the recorded potential results from a single S-component, a single R
      component, or a single intermediate ('decisional' or D-) component related to the
      transition of the two stochastically independent stages. If it can be assumed
      that the evoked potential is the result of a linear summation of an S-component
      and an R-component, then there is a unique recovery into these two components,
      such that the reconstructed waveform on an individual trial is a superposition of
      the two components with their relative offset determined by the RT of that trial
      and the ensemble average is the experimentally obtained s-locked and r-locked ERP
      waveforms. Two independent methods can be used to recover those components, one
      based on Fourier transform techniques which was first proposed by Hansen (1983)
      in the context of ERP component isolation and the other based on a recursive
      iteration approach through which the contamination of the R or S-component is
      successively removed from the s-locked or r-locked ERP waveforms, respectively.
      The iterative procedure is analytically proven to converge to the Fourier-based
      solution, demonstrating the equivalence of the two approaches. Finally, if the
      condition of a single intermediate D-component is satisfied, then one can recover
      this component waveform along with the probability distributions of the relative
      durations of the two underlying linear stages; however, there is always an
      equivalent pair of S- and R-component which also satisfy the same data set (s
      locked and r-locked ERP waveforms and the overall RT distribution). In this case,
      the S/R-component assumption and the D-component assumption cannot be
      distinguished solely on the ground of the available data set. The technique
      developed here outlines the assumptions and the boundary conditions upon which
      ensemble ERP waveforms are to be analyzed and interpreted in terms of processing
      mechanisms related to stimulus, to response, or to the transition between the
      two.

PMID- 9606051
TI  - Thin slice CNS explants maintained on collagen-coated culture dishes.
AB  - We have developed a simple and inexpensive procedure for explant culture termed
      'thin slice culture' that relies on the use of thin sections of CNS tissue ( < or
      = 150 microm) which adhere directly to the bottom of collagen-coated culture
      dishes (or glass coverslips within culture dishes). Microscopic visualization and
      tissue oxygenation are enhanced due to the reduced slice thickness, and the
      reduced volumes of incubation media required lessen the amount of expensive
      agents used (e.g. growth factors). We show that thin slice cultures of spinal
      cord, brainstem and hippocampus remain viable for at least several weeks and are
      suitable for many experimental approaches including time-dependent studies,
      immunocytochemistry and electrophysiology.

PMID- 9606052
TI  - A novel and rapid method for culturing pure rat spinal cord astrocytes on
      untreated glass.
AB  - Astrocytes are the major population of glial cells, and are key players in the
      development, maintenance, and functioning of the central nervous system (CNS).
      Their potential as targets of therapeutic intervention following CNS injury makes
      the elucidation of their cellular and subcellular physiology a primary research
      goal. Well defined and pure cell culture systems are required to examine
      astrocytic physiology, biochemical pathways and underlying responses to
      pathophysiologically altered conditions. Previously published protocols for
      establishing primary astrocyte cultures are time- and resource-consuming or
      suffer high contamination from other undesired cell types. Here we describe a new
      and simple procedure for producing highly pure ( > 99%) rat primary astrocyte
      cultures. The method involves a simple mechanical dissociation of harvested
      spinal cord tissue through a porous membrane and the subsequent plating of the
      cells on plain, untreated glass coverslips. Astrocytes adhere very well to the
      untreated glass while other cell types require a substrate such as poly-L-lysine.
      The method described here is, therefore, ideal for experiments which require
      highly pure astrocyte cultures.

PMID- 9606053
TI  - Tracing of a neuronal network in the locust by pressure injection of markers into
      a synaptic neuropil.
AB  - Central neuronal circuits of vertebrates have often been investigated using
      injection of markers into synaptic neuropils, whereas similar techniques have
      rarely been applied in invertebrates. In this study we tested several
      neuroanatomical tracers for their ability to mark central neuronal circuits in
      insects, using the well described auditory network of the locust, Locusta
      migratoria. After physiological localization of an auditory neuropil various
      tracers were pressure injected. Horseradish peroxidase, dextrans (3 and 10 kDa)
      and especially biocytin and neurobiotin were effectively incorporated by auditory
      interneurons, which resulted in their extensive labeling. Postsynaptic regions
      turned out to be the major, if not exclusive sites of uptake of injected markers,
      which is deduced from two lines of evidence: (i) for labeling of identified
      auditory neurons it was necessary to apply the tracer to postsynaptic sites of
      the neuron; (ii) only a few non-auditory neurons were labeled (probably by
      lesioning axons during electrode impalement). No evidence could be found for an
      activity dependent uptake. We conclude that pressure injection of certain tracers
      into synaptic areas can be used to identify central nervous circuits in insects.

PMID- 9606054
TI  - In vivo detection of experimentally induced cortical dysgenesis in the adult rat
      neocortex using optical coherence tomography.
AB  - Imaging cerebral structure in vivo can be accomplished by many methods, including
      MRI, ultrasound, and computed tomography. Each offers advantages and
      disadvantages with respect to the others, but all are limited in spatial
      resolution to millimeter-scale features when used in routine applications.
      Optical coherence tomography (OCT) is a new, high resolution imaging technique
      which uses light to directly image living tissue. Here, we investigate the
      potential use of OCT for structural imaging of the fully developed mammalian
      cerebral cortex. In particular, we show that OCT can perform in vivo detection of
      neocortex and differentiate normal and abnormal cortical anatomy. We present the
      results of detailed optical coherence tomographic (OCT) observations of both
      normal and abnormal rat neocortex obtained in vivo. Comparative histologic
      analysis shows excellent correlation with the OCT tomograms.

PMID- 9606055
TI  - Pharmacological characterisation of the recombinant human CRF binding protein
      using a simple assay.
AB  - We present the pharmacological characterisation of the recombinant human
      corticotropin releasing factor binding protein (hCRF-BP) using a simple assay. In
      this assay we employed [3H]urocortin as the radioligand and, as a means to
      separate bound and free ligand, adsorption to activated charcoal. Using this
      method, approximately 60-70% of total binding was specific. Kinetic analysis
      revealed that association of specific [3H]urocortin binding was monophasic and
      slow and that the binding was irreversible. Saturation analysis showed a single
      saturable site of relatively high density (94 fmol per 10 microl of medium from
      cells transfected with the recombinant CRF binding protein). The apparent Kd for
      [3H]urocortin binding of 0.25 nM is similar to previously reported affinities of
      rat urocortin for hCRF-BP. A range of CRF-related peptides potently competed for
      specific [3H]urocortin binding. The rank order of potency of these agents was
      human/rat CRF = urotensin 1 > human urocortin > CRF6-33 > sauvagine > ovine CRF.
      The non-peptide CRF1 receptor antagonists CP 154,526 (N-butyl-N-[2,5-dimethyl-7
      (2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]p yri midin-4-yl]-N-ethylamine) and SC
      241 ([3-(2-bromo-4-isopropyl-phenyl)-5-methyl-3H-[1,2,3]triazo lo[4,5-d]pyrimidin
      7-yl]-bis-(2-methoxy-ethyl)-amine) were not active at the highest concentration
      tested (10(-6) M). We conclude that this is a simple and accurate assay for
      characterisation of the pharmacology of the recombinant CRF-BP. This assay should
      assist with further study of the pharmacology and function of the CRF-BP.

PMID- 9606056
TI  - Cytochrome c oxidase assay in minute amounts of human skeletal muscle using
      single wavelength spectrophotometers.
AB  - Determination of cytochrome c oxidase (COX; EC 1.9.3.1) activity in human
      mitochondria presents several technical difficulties which result in a large
      intra- and interlaboratory variability, especially when a single wavelength
      spectrophotometer (SWS) is used, as is generally done in most laboratories in the
      context of screening procedures for the detection of respiratory chain
      deficiencies. We studied the experimental conditions of COX assay in human
      skeletal muscle mitochondria using a SWS in order to define the optimal
      conditions for the assay and compared these results with those obtained using a
      double wavelength spectrophotometer (DWS). We demonstrate that a low intra
      individual variability of COX assay can be obtained with SWS by: (1) using manual
      stirrers to avoid the formation of bubbles in the mixture; (2) preincubating
      mitochondria and laurylmaltoside before the addition of cytochrome c, which
      prevents light scattering secondary to mitochondrial swelling; and (3) using low
      amounts (1-2 microg) of mitochondrial protein to extend and linearize the
      reaction rate. Under these experimental conditions, the concordance between SWS
      and DWS was very good (R=0.975).

PMID- 9606057
TI  - Evidence for a medial K+ recycling pathway from inner hair cells.
AB  - K+ effluxed from outer hair cells and their nerves is thought to flow laterally
      to strial marginal cells for recycling into scala media. Observations reported
      here provide evidence that K+ effluxed from inner hair cells and inner radial
      nerves travels medially through border cells, inner sulcus cells (ISCs), limbal
      fibrocytes and interdental cells (IDCs) for return to endolymph. Morphologic
      features of ISCs in the medial route resembled those of Hensen and Claudius cells
      in the lateral indicating an ion transport role for ISCs like that of Hensen and
      Claudius cells. Na,K-ATPase in plasmalemma of IDCs testified to their capacity to
      resorb and transport K+ through their known gap junctions. IDCs were
      differentiated into three subgroups. The most lateral IDCs formed short and long
      columns. Long columns contacted the medialmost ISC inferiorly and the
      undersurface of the tectorial membrane superiorly providing thereby a potential
      transcellular route for K+ transit from ISCs to endolymph. Short columns faced
      inner sulcus below and tectorial membrane above and accordingly possessed cells
      with opposite polarity at the bottom and top of the column. Short columns thus
      appeared situated to resorb electrolytes from limbal stroma for release into
      inner sulcus and beneath tectorial membrane at opposite ends of the column. The
      central IDCs were positioned for resorbing and transporting K+ effluxing from the
      Na,K-ATPase-rich stellate fibrocytes which spread toward the IDCs from near the
      inner sulcus. The most medial IDCs lined cuplike invaginations near the
      attachment of Reissner's membrane and lay apposed to light fibrocytes located
      between supralimbal fibrocytes and the medial IDCs. Content of Na,K-ATPase and
      position in the K+ transport route likened the limbal stellate fibrocytes to the
      spiral ligament type II fibrocytes and supralimbal fibrocytes to suprastrial
      fibrocytes in the lateral wall. From content of creatine kinase and position in
      the transport path, limbal light fibrocytes appeared analogous to spiral ligament
      type I fibrocytes. The additional finding that limbal fibrocytes showed unchanged
      or upregulated Na,K-ATPase immunoreactivity in aged gerbils with strial atrophy
      provided further evidence for an independent medial transport route and for the
      survival of inner hair cells in presbyacusis.

PMID- 9606058
TI  - Head-related transfer functions of the barn owl: measurement and neural
      responses.
AB  - Sounds arriving at the eardrum are filtered by the external ear and associated
      structures in a frequency and direction specific manner. When convolved with the
      appropriate filters and presented to human listeners through headphones,
      broadband noises can be precisely localized to the corresponding position outside
      of the head (reviewed in Blauert, 1997). Such a 'virtual auditory space' can be a
      potentially powerful tool for neurophysiological and behavioral work in other
      species as well. We are developing a virtual auditory space for the barn owl,
      Tyto alba, a highly successful auditory predator that has become a well
      established model for hearing research. We recorded catalogues of head-related
      transfer functions (HRTFs) from the frontal hemisphere of 12 barn owls and
      compared virtual and free sound fields acoustically and by their evoked neuronal
      responses. The inner ca. 1 cm of the ear canal was found to contribute little to
      the directionality of the HRTFs. HRTFs were recorded by inserting probetube
      microphones to within about 1 or 2 mm of the eardrum. We recorded HRTFs at
      frequencies between 2 and 11 kHz, which includes the frequencies most useful to
      the owl for sound localization (3-9 kHz; Konishi, 1973). Spectra of virtual
      sounds were within +/- 1 dB of amplitude and +/- 10 degrees of phase of the
      spectra of free field sounds measured near to the eardrum. The spatial pattern of
      responses obtained from neurons in the inferior colliculus were almost
      indistinguishable in response to virtual and to free field stimulation.

PMID- 9606059
TI  - Volume displacement of the gerbil eardrum pars flaccida as a function of middle
      ear pressure.
AB  - The pars flaccida (PF) is a small region of the eardrum, with elasticity and
      histology completely different from the rest of the membrane, which has often
      been attributed a pressure regulating function for the middle ear (ME). In this
      paper, the volume displacement of the PF as a function of ME pressure is
      discussed. The deformation of the PF was measured in vitro in five Mongolian
      gerbil ears, by means of an opto-electronic moire interferometer. Volume
      displacement was determined at small intervals in three sequential pressure
      cycles, in the range of +/- 0.4 kPa, +/- 2 kPa, and again +/- 0.4 kPa. The
      displacement was found to be a highly non-linear function of pressure, with a
      strong increase up to 0.4 kPa ME over- or underpressure and remaining nearly
      unchanged for pressures beyond 0.4 kPa. In all animals, maximal volume
      displacement was less than 0.5 microl, or 0.2% of total ME air volume. Clear
      hysteresis was found between the deformations at the same pressure level in the
      increasing and decreasing parts of the pressure cycles. Membrane behavior in the
      first 0.4 kPa pressure cycle was significantly different from that in the second
      0.4 kPa cycle, which followed the 2 kPa pressure cycle. The results indicate that
      the ME pressure change regulation function of the PF is limited to very small
      pressure changes of a few hundred Pa around ambient pressure, and that larger ME
      pressures cause at least short-term changes in the membrane's behavior.

PMID- 9606060
TI  - Additional pharmacological evidence that endogenous ATP modulates cochlear
      mechanics.
AB  - In the cochlea, outer hair cells (OHCs) generate the active cochlear mechanics
      whereas the supporting cells, such as Deiters' cells and Hensen's cells, may play
      a role in both the active and passive cochlear mechanics. The presence of
      receptors for adenosine triphosphate (ATP) on OHCs, Deiters' cells and Hensen's
      cells indicates that endogenous ATP may have a role in cochlear mechanics. To
      explore this possibility, the effects of the ATP antagonist, pyridoxal-phosphate
      6-azophenyl-2',4'-disulfonic acid (PPADS), were studied in guinea pig both in
      vitro on isolated OHCs, Deiters' cells, Hensen's cells and pillar cells using the
      whole-cell configuration of the patch-clamp technique, and in vivo on sound
      evoked cochlear potentials (cochlear microphonic, CM; summating potential, SP;
      compound action potential, CAP) and distortion product otoacoustic emissions
      (DPOAEs) using cochlear perilymphatic perfusion. Results show that PPADS (100
      microM) reduced the inward current evoked by 5-10 microM ATP in OHCs, Deiters'
      cells, Hensen's cells and pillar cells. This effect of PPADS was slow in onset
      and was slowly reversed to a varying degree in the different cell types. In vivo
      application of PPADS in increasing concentrations reduced the sound evoked CAP,
      SP and increased N1 latency starting at about 0.33 mM (SP) and 1 mM (CAP and N1
      latency). PPADS (0.33-1 mM) reversibly suppressed the initial value of the
      quadratic DPOAE and reversed the 'slow decline' in the quadratic DPOAE that
      occurs during continuous stimulation with moderate level primaries. These
      results, together with the similar effects of the ATP antagonist suramin reported
      previously (Skellett et al., 1997), may be evidence that endogenous ATP acting on
      cells in the organ of Corti alters cochlear mechanics.

PMID- 9606061
TI  - Development of the endolymphatic sac and duct in the Japanese red-bellied newt,
      Cynops pyrrhogaster.
AB  - The development and maturation of the endolymphatic sac (ES) and duct (ED) were
      studied in the newt Cynops pyrrhogaster. The ES first appears as an oval capsule
      at the dorsal-medial tip of the otic vesicle at stage 39, about 11 days after
      oviposition. The ES consists of polymorphous epithelial cells with a minimum of
      cytoplasm. The intercellular space (IS) between the epithelial cells is narrow
      and has a smooth surface. At stage 44, the size of the ES increases as many
      vacuoles in the IS become filled. At stage 46, 18 days after oviposition, the ES
      elongates markedly and a slit-like lumen is found in the ES. The epithelium
      contains a few cell organelles which are scattered in the cytoplasm. The vacuoles
      in the IS are fused, which expands the IS. Two days later (stage 48), floccular
      material (endolymph) is present in the expanded lumen. The IS dilates and has a
      wide and irregular appearance. At stage 50, approximately 26 days after
      oviposition, the ES extends and expands significantly and crystals (otoconia) can
      now be seen in the widened lumen of the ES. The cytoplasm of the cuboidal
      epithelial cells contains an abundance of vesicles surrounded by ribosomes and
      Golgi complexes. Intercellular digitations are formed in the expanded IS. At
      stage 54, the ES forms a large bellow-like pouch. Numerous otoconia accumulate in
      the lumen. Free floating cells and cell debris can be seen in the lumen at this
      stage. The epithelial cells contain numerous cytoplasmic organelles which are
      evenly distributed in the cytoplasm. Granules are found in the apical and lateral
      cytoplasm. The IS is loose and displays a labyrinthine appearance. The primitive
      ED first appears as a connection between the ES and the saccule but no lumen is
      present inside at stage 39. At stage 46, a narrow lumen is formed in the ED,
      which corresponds to the formation of the ES lumen. At stage 50, as the ED
      extends, floccular material is seen in the lumen. At stage 54, the ED bears
      numerous microvilli on its luminal surface. Otoconia and endolymph are present in
      the ED. Tight junctions between the epithelial cells are formed at stage 46. A
      fully developed intercellular junctional complex is produced at stage 54. Based
      on the development of the ES and ED, the maturation of function of the ES and ED
      are discussed.

PMID- 9606062
TI  - Noise-induced threshold shift dynamics measured with distortion-product
      otoacoustic emissions and auditory evoked potentials in chinchillas with inner
      hair cell deficient cochleas.
AB  - Chinchillas (n = 6) were treated with carboplatin and, following a 30-day
      recovery period, were exposed to a 115 dB peak SPL impact noise presented at a
      rate of l/s for 6 h/day for 10 days. A second group (n = 6) received only the
      noise treatment. Cubic distortion product otoacoustic emissions (2f1-f2) and
      auditory evoked potential (AEP) detection thresholds in response to tone bursts
      were measured before and 30 days after drug treatment and following the first and
      10th day of the noise exposure. Thirty days after the final exposure day,
      permanent changes in AEP detection thresholds and emissions were measured and
      cochleograms constructed. The drug treatment eliminated over 80% of the inner
      hair cells (IHC) in the cochlea, leaving the outer hair cell (OHC) population
      essentially intact prior to the interrupted noise exposure. The drug treatment
      alone had very little or no effect on AEP detection thresholds and emission
      metrics. Following the noise exposure, the IHC-deficient animals showed clear
      'toughening' effects in the AEP and emission measures which were the same as
      measured in the group receiving only the noise. After a 30-day post-exposure
      recovery period. AEP thresholds were elevated about 10 dB at the low frequencies
      in the drug-noise group whereas emissions returned to near normal despite the
      massive IHC losses. These results are consistent with the idea that an intact OHC
      population is required for toughening. However, sound-evoked efferent pathways
      activated by the few remaining IHCs (approximately 20%) which, in this
      preparation, are distributed throughout the cochlea, may still contribute
      significantly to the toughening phenomena.

PMID- 9606063
TI  - Tone burst-evoked otoacoustic emissions in cats with acoustic overstimulation and
      anoxia.
AB  - Transient evoked otoacoustic emissions (TEOAE) produced by a 2 kHz tone burst
      could be detected in 30 out of 37 ears (81% detectability) in 21 cats. The
      amplitude of tone burst-evoked TEOAE was saturated at a stimulus level between 45
      and 50 dB SPL and the latency time of peak amplitude was 6.23 ms on average (5.53
      7.28 ms). The effects of pure tone overstimulation and short-term anoxia on the
      tone burst-evoked TEOAE in cats were evaluated. A permanent detection threshold
      shift of the TEOAE was confirmed at 24 h and 1 week after the overstimulation at
      125 dB SPL. In these cases, damaged first row outer hair cells and inner hair
      cells were observed over an average length of 3.3 mm (16% of the entire cochlear
      length) by scanning electron microscopy. These findings suggested that the TEOAE
      can detect localized cochlear hair cell damage. A temporary detection threshold
      shift of the TEOAE was observed after the overstimulation at 105 dB SPL, and the
      threshold shift recovered in 107.5 min on average. In the short-term anoxia
      trial, the TEOAE amplitude started to decrease 45-90 s after the anoxia and
      recovered completely when the duration of anoxia was under 1 min. However, the
      TEOAE amplitude did not recover pre-anoxia values (it remained below 80% of its
      initial value) after 5 min when the anoxia was over 2 min. These findings
      demonstrated that the detection threshold and amplitude of the TEOAE were also
      affected by metabolic changes of the cochlear hair cells. Tone burst-evoked TEOAE
      are useful for the evaluation of localized histological and functional damage of
      the cochlear hair cells.

PMID- 9606064
TI  - Ca2+-dependence and nifedipine-sensitivity of vascular tone and contractility in
      the isolated superfused spiral modiolar artery in vitro.
AB  - The regulation of the vascular diameter of the spiral modiolar artery may play a
      major role in the regulation of cochlear blood flow and tissue oxygenation since
      the spiral modiolar artery provides the main blood supply to the cochlea. The
      goal of the present study was to determine whether vascular tone and
      contractility of the spiral modiolar artery depend on the presence of
      extracellular Ca2+ and involves nifedipine-sensitive Ca2+ channels. The spiral
      modiolar artery was isolated and superfused in vitro and the diameter was
      measured continuously by video microscopy. Isolated segments of the spiral
      modiolar artery had an outer diameter of 61 +/- 3 microm (n = 59) and displayed
      vasomotion characterized by 5-15 clearly distinguishable constrictions per min.
      Removal of Ca2+ from the superfusion medium caused a reversible relaxation and
      cessation of vasomotion and was used to determine the magnitude of basal vascular
      tone. The basal vascular tone consisted of a sustained reduction of the vascular
      diameter to 95.1 +/- 0.3% (n = 51) of the maximal diameter in Ca2+-free medium.
      Nifedipine reduced the basal vascular tone with an IC50 of (1.1 +/- 0.3) x 10(
      9)) M although 22% of the basal vascular tone was insensitive to nifedipine.
      Elevation of the K+ concentration from 3.6 to 150 mM caused a transient
      vasoconstriction which was dependent on the presence of extracellular Ca2+.
      Nifedipine fully inhibited K+-induced vasoconstriction with an IC50 of (2.0 +/-
      0.7) x 10(-9) M. Norepinephrine (10(-4) M) caused a transient vasoconstriction
      and an increase of vasomotion at branch points of the spiral modiolar artery.
      Norepinephrine-induced vasoconstriction was fully inhibited in the absence of
      Ca2+ and partially inhibited by 10(-7) M nifedipine. These observations suggest
      that the spiral modiolar artery contains voltage-dependent nifedipine-sensitive
      Ca2+ channels which are involved in the maintenance of basal vascular tone as
      well as in the mediation of K+- and norepinephrine-induced contractility.
      Further, the data suggest that cytosolic Ca2+ stores, if present in the spiral
      modiolar artery, are of limited capacity compared to other vessels.

PMID- 9606065
TI  - Exposure to an augmented acoustic environment alters auditory function in hearing
      impaired DBA/2J mice.
AB  - The effects of exposure to an augmented acoustic environment (AAE) on auditory
      function were evaluated using DBA/2J (DBA) mice, a strain that exhibits high
      frequency hearing loss beginning around the time of weaning/adolescence (between
      3-4 weeks of age) and becoming severe by 2-3 months of age. Mice were exposed 12
      h per night for 10 nights to a 70 dB SPL broad-band noise AAE at one of three age
      periods ranging from the onset of hearing loss (25-35 days of age) to more severe
      degrees of hearing loss (35-45 days and 45-55 days); control mice did not receive
      the AAE. C57BL/6J (C57) mice of the same ages provided normal-hearing. age
      matched mice in both exposed and control conditions. The auditory brainstem
      response (ABR), acoustic startle response amplitude, and prepulse inhibition
      (PPI) were used to assess the auditory system. The AAE had significant effects on
      DBA mice, but had no effect on normal-hearing C57 mice. For the most part, AAE
      exposure resulted in improved auditory performance in DBA mice (better PPI, lower
      ABR thresholds, bigger startle amplitudes). However, the age of the mice and/or
      severity of hearing loss proved to be an important variable; improvement of PPI
      occurred only when the AAE was initiated later in the course of hearing loss (35
      days of age or older); in contrast to this, beneficial effects on ABR thresholds
      occurred only when the AAE was initiated early in the course of hearing loss (<
      45 days of age).

PMID- 9606066
TI  - Na-K-Cl cotransporter expression in the developing and senescent gerbil cochlea.
AB  - Changes in the cellular expression pattern of the Na-K-Cl cotransporter (NKCC)
      were investigated during postnatal development and with advancing age in the
      gerbil cochlea. At birth, faint immunostaining for NKCC was discernable in the
      developing stria vascularis (StV), Reissner's membrane, interdental cells and
      some relatively undifferentiated cells lining the cochlear partition. Between 2
      and 4 days after birth (DAB) immunostaining persisted and increased in the future
      interdental, inner and outer sulcus and claudius cells but then disappeared from
      these sites by 8 DAB. In contrast, NKCC immunoreactivity in the StV increased
      progressively during development and approached adult levels by 12 DAB.
      Immunostaining for NKCC in subpopulations of fibrocytes in the inferior portion
      of the spiral ligament, the suprastrial region and the spiral limbus was first
      detectable between 10 and 12 DAB and staining intensity reached adult levels
      around 16 DAB. Changes in NKCC expression with advancing age generally mimicked
      those previously observed for Na,K-ATPase in focal regions of atrophic lateral
      wall. Diminished immunostaining was first seen in the StV, presumably associated
      with the involution of the marginal cell's basolateral processes. Further atrophy
      culminated in complete loss of immunostaining in the StV and an associated down
      regulation of NKCC expression in spiral ligament transport fibrocytes. The marked
      similarities in the developmental and age-related expression patterns of NKCC and
      Na,K-ATPase point to a high level of functional cooperativity between these two
      ion transport mediators, which together provide an efficient mechanism for
      generating and maintaining high K+ levels in endolymph and the endocochlear
      potential.

PMID- 9606067
TI  - Immunohistochemical investigation of enkephalins in the human inner ear.
AB  - Enkephalins are generally considered as neuropeptides in the central and
      peripheral nervous system of mammals bound to three large precursor molecules.
      Several animal studies demonstrated the distribution of met- and leu-enkephalin
      like immunoreactivities in neurons and terminals of the lateral olivocochlear
      system. The immunostainings in the medial system are more controversial. No data
      about the presence of different enkephalin sequences in the vestibular efferent
      terminals are known. In the present study, the ultrastructural localization and
      distribution of immunoreactivities for six different antibodies against met- and
      leu-enkephalins in the human cochlear and vestibular periphery were investigated.
      A modified method of pre-embedding immunoelectronmicroscopy was applied. Met- and
      leu-enkephalin-like immunoreactivities were observed in the efferent terminals of
      the human outer and inner hair cell region. Using different met- and leu
      enkephalin antibodies, the distribution of immunoreactivities remained similar.
      In the five human vestibular endorgans, enkephalin-like immunostaining was
      absent.

PMID- 9606068
TI  - Accurate binaural mirroring of spontaneous otoacoustic emissions suggests
      influence of time-locking in medial efferents.
AB  - Spontaneous otoacoustic emissions (SOAEs) of nearly identical acoustic frequency
      in both ears are a common observation, but it is unknown if this binaural
      mirroring effect is random, artefactual, genetic, developmental, or of other
      origin. The available raw data of all human SOAE surveys were pooled, and the
      intervals of all possible binaural emission pairs (N = 9555) were listed
      according to size on the Cent-scale (1 Cent = 1/100 semitone = 1/1200 octave).
      Statistical analysis showed (1) a slight broad-band mirroring in the 0-100 Cent
      range (P < 0.05), and (2) a strong narrow-band mirroring (NBM) in the 0-20 Cent
      range (P < 0.001). Negative results in a detailed SOAE cluster detection program
      excluded experimental artefacts as causes of NBM. Analysis of the large subgroup
      of twin data excluded genetic and intrauterine developmental causes. Systemic
      developmental causes are unrealistic, as 20 Cent corresponds to only
      approximately 80 microm on the cochlear map. Analysis of infant data indicated
      that the effect may be introduced after birth by secondary factors. Interaural
      crosstalk was examined but had to be rejected. It is suggested that bilaterally
      spreading period information in the medial olivocochlear system influences outer
      hair cells of the same best frequency in both ears very similarly. Evidence
      concerning possible effects on electromotility is discussed, and experimental
      tests are proposed.

PMID- 9606069
TI  - Masking of tones and speech by Schroeder-phase harmonic complexes in normally
      hearing and hearing-impaired listeners.
AB  - Tone detection and sentence recognition were measured for normally hearing and
      hearing-impaired listeners using maskers consisting of harmonic series with
      components summed in positive or negative Schroeder phase. Each task was carried
      out with the signal set at 60, 70, or 80 dB SPL. For listeners with normal
      hearing, positive Schroeder-phase complexes masked tones and sentences less than
      negative Schroeder-phase maskers. In the two experimental tasks, to achieve the
      same amount of masking, positive Schroeder-phase complexes had to be set as much
      as 12-15 dB higher than negative Schroeder-phase complexes. Large phase effects
      were observed on both tasks at all three test levels. The two maskers were more
      nearly equal in effectiveness in the presence of cochlear damage. The findings
      support an interpretation that involves differences in the shape of the basilar
      membrane waveform generated by each masker and active cochlear processing which
      enhances the internal signal-to-masker ratio for signals presented in the
      positive Schroeder masker. This spectral enhancement appears to require nonlinear
      active gain that is characteristic of normal auditory processing at moderate
      presentation levels. The results of the sentence recognition task suggest that
      group differences observed in tone detection transfer fairly directly to speech
      perception under masking.

PMID- 9606070
TI  - Specific sound-induced noradrenergic and serotonergic activation in central
      auditory structures.
AB  - We have studied the noradrenergic and serotonergic changes induced by white noise
      stimulation at 70, 90 or 110 dB SPL for 45 min, in cochlear nuclei, inferior
      colliculus (IC), primary auditory cortex (PAC) and as a comparison in locus
      coeruleus (LC) and raphe dorsalis using HPLC. Both noradrenergic and serotonergic
      pathways were activated in the dorsal+posteroventral cochlear nuclei (DCN+PVCN)
      without changes in the anteroventral cochlear nucleus (AVCN) and IC. In the
      DCN+PVCN the noradrenergic activation was restricted to animals exposed to 70 dB
      SPL whereas the increase of serotonin content was intensity-dependent. In PAC
      serotonergic activation was observed only after 70 dB SPL exposure. These data
      suggest that in physiological conditions (70 dB SPL) noradrenergic and
      serotonergic regulation of the processing of auditory information occurs
      specifically in the dorsal cochlear nucleus where the control of incoming
      information to higher auditory structures takes place (i.e. IC and PAC). We
      suggest that the serotonergic activation in the primary auditory cortex for 70 dB
      SPL sound stimulation could be related to the fact that low-intensity white noise
      stimulation could be the most plastic-demanding processing in the auditory
      cortex.

PMID- 9606071
TI  - The effect of explantation and neomycin on hair cells and supporting cells in
      organotypic cultures of the adult guinea-pig utricle.
AB  - Recent reports suggest that immature hair bundles are observed following
      aminoglycoside-induced hair-cell loss in the mammalian utricle in vitro as well
      as in vivo. It is therefore important to document the initial morphological
      changes associated with both culturing and aminoglycoside application so that
      degeneration can be clearly distinguished from regeneration. In this study,
      utricles from adult guinea pigs were maintained in culture for either 3 or 8
      days, half being exposed to neomycin for days 2 and 3. They were then processed
      for microscopical examination and compared with control utricles from animals of
      the same age. The numbers of hair-cell and supporting-cell nuclei were counted
      and hair-cell morphology assessed. Bundles were classified as having either
      stepped (SHB) or unstepped (UHB) stereocilia, and their density determined. The
      numbers of hair-cell, but not supporting-cell, nuclei declined significantly
      compared with controls in both untreated and treated explants, the greatest
      reduction occurring 5 days after neomycin administration. The density of SHBs
      also declined but there was no significant change in UHB density, resulting in a
      residual population of hair bundles of more immature appearance in both untreated
      and treated utricles in vitro than in vivo. Although degenerative events such as
      hair-cell ejection from, or retraction into, the sensory epithelium were
      observed, no evidence of regeneration was found.

PMID- 9606072
TI  - The nitric oxide/cyclic GMP pathway: a potential major regulator of cochlear
      physiology.
AB  - The nitric oxide (NO)/cyclic guanosine monophosphate (GMP) pathway is now
      recognized as a major regulatory system in cell physiology and tissue
      homeostasis. This pathway may control processes as diverse as muscle relaxation,
      gut peristalsis, neurotransmission and hormonal secretion. It is also involved in
      the development and function of sensory systems such as vision and olfaction.
      This review will detail the NO/cyclic GMP pathway, evaluate studies in the
      auditory system and discuss its potential participation in cochlear blood flow,
      supporting cell physiology and excitotoxicity.

PMID- 9606073
TI  - Seven practice profit centers: the team's role in practice success.

PMID- 9606074
TI  - The use of primary care general dental anaesthesia is no longer declining.

PMID- 9606075
TI  - GDPs should examine their methods of communication to non-attenders.

PMID- 9606076
TI  - A simple technique for the removal of mottled enamel using readily available
      materials.

PMID- 9606077
TI  - Do not confuse the bone loss of periodontitis with root exposure due to
      supereruption. Factors affecting the lifespan of the human dentition in Britain
      prior to the seventeenth century.

PMID- 9606078
TI  - The role of DNA bending in Cro protein-DNA interactions.
AB  - Binding energy of DNA-Cro protein complexes is analyzed in terms of DNA
      elasticity, using a sequence-dependent anisotropic bendability (SDAB) model of
      DNA, developed recently [M.M. Gromiha, M.G. Munteanu, A. Gabrielian and S.
      Pongor, J. Biol. Phys. 22(1996) 227-243.]. The protein is considered to bind
      aspecifically to DNA that reduces the freedom of movement in the DNA molecule. In
      cognate DNA, the Cro protein moves on to form specific interactions and bends
      DNA. A comparison of the experimental data [Y. Takeda, A. Sarai and V.M. Rivera,
      Proc. Natl. Acad. Sci. U.S.A. 86 (1989) 439-443.] with the calculated DNA
      stiffness data shows that delta G of the complex formation increases with
      stiffness of the ligand when the interactions are nonspecific ones, while an
      opposite trend is observed for specific binding. Both of these trends are in
      agreement with our approach using the SDAB model. A decomposition of the energy
      terms suggests that binding energy in the nonspecific case is used maily to
      compensate the free energy changes due to entropy lost by DNA, while the energy
      of specific interactions provide enough energy both to bend the DNA molecule and
      to change the conformation of the Cro protein upon ligand binding.

PMID- 9606079
TI  - Recruiting family doctors for research studies.

PMID- 9606080
TI  - Proceedings of the International Symposium on In Vivo Body Composition Studies.
      Malmo, Sweden, 18-20 September 1996.

PMID- 9606081
TI  - DXA body composition properties: inherent in the physics or specific to scanner
      type?
AB  - Experimental results with DXA body composition are partly attributable to the DXA
      technology itself (X-ray physics) and partly to the particular implementation
      (Lunar DPX, Hologic QDR, etc). This paper identifies a number of advantages and
      disadvantages of DXA body composition measurement, distinguishing between those
      which are common to all DXA and those which are specific to particular
      instruments.

PMID- 9606082
TI  - Body composition stability in Lunar DPX.
AB  - This study examines how well a Lunar DPX can compensate for certain aging changes
      in its X-ray source. Total body scans were done on a phantom having variable soft
      tissue composition. Aging of the X-ray source was simulated by placing a thin
      aluminum foil over the beam exit window, and by deliberately misadjusting the
      high voltage power supply. The % fat measurement was found to change by up to
      12%, but returned to within about 2% afer recalibration.

PMID- 9606083
TI  - A total body phantom for use with Lunar dual-energy X-ray absorptiometers.

PMID- 9606085
TI  - A new Monte Carlo program for computing low-energy gamma- and X-ray propagation
      in an axially-symmetric XRF system. Swansea In Vivo Analysis and Cancer (SIVAC)
      Group.
AB  - Annular XRF systems, using backscattering geometry, have advantages of
      convenience of use, but it is difficult to predict their sensitivity to
      concentrations of heavy metals ta different depths, or the contribution of
      scattered radiation to the background. A Monte Carlo program has therefore been
      developed to carry out calculations of this type. Several variance-reduction
      techniques are included. Preliminary results for the detection of platinum are
      given.

PMID- 9606084
TI  - Benchmarking the MCNP code for Monte Carlo modelling of an in vivo neutron
      activation analysis system.
AB  - The Monte Carlo computer code MCNP (version 4A) has been used to develop a
      personal computer-based model of the Swansea in vivo neutron activation analysis
      (IVNAA) system. The model included specification of the neutron source (252Cf),
      collimators, reflectors and shielding. The MCNP model was 'benchmarked' against
      fast neutron and thermal neutron fluence data obtained experimentally from the
      IVNAA system. The Swansea system allows two irradiation geometries using 'short'
      and 'long' collimators, which provide alternative dose rates for IVNAA. The data
      presented here relate to the short collimator, although results of similar
      accuracy were obtained using the long collimator. The fast neutron fluence was
      measured in air at a series of depths inside the collimator. The measurements
      agreed with the MCNP simulation within the statistical uncertainty (5-10%) of the
      calculations. The thermal neutron fluence was measured and calculated inside the
      cuboidal water phantom. The depth of maximum thermal fluence was 3.2 cm
      (measured) and 3.0 cm (calculated). The width of the 50% thermal fluence level
      across the phantom at its mid-depth was found to be the same by both MCNP and
      experiment. This benchmarking exercise has given us a high degree of confidence
      in MCNP as a tool for the design of IVNAA systems.

PMID- 9606086
TI  - Proximal and distal measurements of extracellular and total body water by multi
      frequency bio-impedance analysis in surgical patients.
AB  - Measurements of extracellular water (ECW) and total body water (TBW) can be
      useful when assessing the nutritional status of surgical patients. The simple and
      non-invasive nature of bio-impedance techniques may allow repeat measurements to
      assess clinically significant changes in ECW and TBW. We have evaluated bio
      impedance spectroscopy (BIS) and multi-frequency bio-impedance analysis (MFBIA)
      using radioisotope dilution as the independent method.

PMID- 9606087
TI  - Analysis of dual energy X-ray absorptiometry whole body results in children,
      adolescents and young adults.

PMID- 9606088
TI  - Heavy metal toxicology.

PMID- 9606089
TI  - [Chronic relapsing experimental allergic encephalomyelitis in Lewis rats as a
      model of multiple sclerosis].
AB  - Chronic relapsing experimental allergic encephalomyelitis (CR EAE) was induced in
      Lewis rats by inoculation with guinea-pig myelin and complete Freund's aduvant
      followed by treatment with low dose cyclosporin A. Histological, histochemical
      and electron microscopic studies of the lesions during the first and the second
      clinical episodes, as well as during the first and the second remissions,
      revealed inflammation, prominent demyelination, remyelination and gliosis in the
      central nervous system (CNS). This model of CR EAE in the Lewis rats may be a
      useful model for multiple sclerosis.

PMID- 9606090
TI  - Responses of Halobacterium halobium and Sulfolobus solfataricus to hydrogen
      peroxide and N-methyl-N'-nitro-N-nitrosoguanidine [correction of N-methyl-N
      nitrosoguanidine] exposure.
AB  - We have examined the capacity of Halobacterium halobium and Sulfolobus
      solfataricus to withstand the lethal effect of hydrogen peroxide and N-methyl-N'
      nitro-N-nitrosoguanidine [corrected].  We tested a variety of pretreatment
      regimens with both mutagens and all failed to elicit an inducible response to the
      lethal effects of those compounds in either organism. We have observed AP
      endonuclease activity in protein extracts from both organisms. In addition, S.
      solfataricus extracts contain activities that remove 3-methyl-adenine and O(6)
      methyl-guanine from methylated DNA. This is the first report of these DNA repair
      activities in any member of the Archaea.

PMID- 9606091
TI  - Vesicle transport: more work for the Rabs?
AB  - The Rab family of small GTP-binding proteins has long been implicated in the
      docking and fusion of transport vesicles with their target membranes. Recent
      evidence, however, suggests that some Rabs may play an additional role in
      transport vesicle formation.

PMID- 9606092
TI  - Bracing and heel wedging for unicompartmental osteoarthritis of the knee.

PMID- 9606093
TI  - Notes of the American Society for Clinical Pharmacology and Therapeutics. A
      letter to the members.

PMID- 9606094
TI  - Aspirin, NSAIDS, and colon cancer prevention: mechanisms?

PMID- 9606095
TI  - The search for pathogenic antigens in ulcerative colitis.

PMID- 9606096
TI  - AAPC: are current screening recommendations enough?

PMID- 9606097
TI  - Does growth hormone and glutamine enhance bowel absorption?

PMID- 9606098
TI  - Hepatic iron index: how useful is it?

PMID- 9606099
TI  - Gastrin is the most important factor in ECL tumorigenesis.

PMID- 9606100
TI  - Rates of colonoscopic perforation in current practice.

PMID- 9606101
TI  - [Pain-free circumcision].

PMID- 9606102
TI  - Practice parameters for the psychiatric assessment of children and adolescents.
      American Academy of Child and Adolescent Psychiatry.
AB  - These practice parameters have been developed by the American Academy of Child
      and Adolescent Psychiatry as a guide for clinicians evaluating psychiatric
      disorders in children and adolescents. The document focuses on the assessment,
      diagnostic, and treatment planning process, emphasizing a developmental
      perspective. The assessment process is intended for all children and adolescents
      presenting with psychiatric disorders that impair emotional, cognitive, physical,
      or behavioral functioning to assist the clinician in arriving at accurate
      diagnoses and in appropriate treatments. Details of the parent and child
      interviews are presented as well as an outline of specific areas of inquiry
      necessary for this process. The use of standardized tests and rating scales is
      addressed. These parameters were previously published in J. Am. Acad. Child
      Adolesc. Psychiatry, 1995, 31:1386-1402.

PMID- 9606103
TI  - Isoproterenol evokes extracellular Ca2+ spikes due to secretory events in
      salivary gland cells.
AB  - Secretory cells should in principle export substantial amounts of calcium via
      exocytosis since Ca2+ is sequestered in secretory granules. Based on a new
      technique for measurements of the extracellular calcium concentration in the
      vicinity of the cell membrane and on the droplet techniques we have monitored the
      rate of calcium extrusion from salivary gland acinar cells. Isoproterenol (ISP),
      a beta-adrenergic agonist and powerful secretogogue, evoked no change in the
      cytosolic free Ca2+ concentration ([Ca+]i but induced vigorous extracellular Ca+
      concentration ([Ca2+]o) spiking. The absence of [Ca2+]i elevation and the
      pulsatile nature of the changes in [Ca2+]o indicate that these spikes are most
      likely due to calcium release from secretory granules. The cholinergic agonist
      acetylcholine (ACh), which induces moderate secretion, evoked a marked rise in
      [Ca2+]i and a smooth rise in [Ca2+]o, most likely induced by plasma membrane
      calcium pumps, on which shortlasting [Ca2+]o spikes were superimposed. The rate
      of ISP-induced calcium efflux was very substantial. The calculated calcium loss
      during the first 100 s of supramaximal stimulation corresponded to a reduction of
      the total cellular calcium concentration of approximately 0.4 mm. We conclude
      that in salivary glands, calcium release via exocytosis is one of the main
      mechanisms extruding calcium from cells to the extracellular milieu.

PMID- 9606104
TI  - Defining acute care medicine for the 21st century. 7th International Conference
      on Emergency Medicine. Vancouver, British Columbia, Canada. March 25-29, 1998.
      Abstracts.

PMID- 9606105
TI  - Putative preneoplastic changes identified by enzyme histochemical and
      immunohistochemical techniques.
AB  - Microscopic evaluation of whole-mount colons stained with methylene blue and/or
      hexosaminidase has identified putative preneoplastic lesions in the colons of
      rodents treated with carcinogen and in the grossly normal colons of humans.
      Enzyme histochemistry with glycol methacrylate sections has permitted the
      identification of putative premalignant lesions in rodent livers, human and
      rodent colons, and human prostates. Immunohistochemistry with paraffin-embedded
      tissues has been used to identify and characterize putative premalignant lesions
      in human colons and prostates.

PMID- 9606106
TI  - Insights about brain tumors gained through immunohistochemistry and in situ
      hybridization of nuclear and phenotypic markers.
AB  - Immunohistochemistry (IHC) has provided major insights about the classification
      of brain tumors by identifying cellular markers of phenotype and about tumor
      growth potential with nuclear markers of proliferation. In situ hybridization
      (ISH) research shows promise for diagnostic applications in tumor classification.
      The avidin-biotin conjugate IHC procedure is highlighted for diagnostic use on
      routinely processed clinical specimens. The immunophenotypes of brain tumors are
      tabulated in reference to their common IHC markers. Tumors that have been
      correctly classified by their IHC phenotypes include the giant-cell glioblastoma,
      primary brain lymphoma, and central neurocytoma. Phenotypes that may be more
      definitively detected by ISH, such as pituitary hormone, immunoglobulin light
      chain, and collagen messages are described. IHC of nuclear proliferation markers
      correlates with grade of malignancy, predicts tumor growth potential, and is
      prognostic for patient survival. The incorporation of bromodeoxyuridine, the
      expression of proliferating cell nuclear antigen, and the expression of Ki-67
      antigen detected by MIB-1 antibody are compared in regard to their cell cycle
      activity and labeling index determinations. Fluorescence in situ hybridization
      (FISH) of brain tumor interphase nuclei and chromosomes is described. Abnormal
      FISH signals of specific chromosomes are associated with different types of brain
      tumors, with different grades of malignancy, and with mesenchymal drift of glioma
      cells in culture.

PMID- 9606107
TI  - Research and Technology Transfer in Computerized Electrocardiology. Proceedings
      of the 22nd annual International Society for Computerized Electrocardiology
      (ISCE) conference. Palm Coast, Florida, USA. April 26-May 1, 1997.

PMID- 9606108
TI  - Mental and manual rotation.
AB  - The relation between mental and manual rotation was investigated in 2
      experiments. Experiment 1 compared the response times (RTs) of mental rotation
      about 4 axes in space with the RTs shown in the same task when participants were
      allowed to reorient the stimuli by means of rotational hand movements. For the 3
      Cartesian axes, RT functions were quantitatively indistinguishable. Experiment 2
      investigated interference between mental rotation and 4 kinds of simultaneously
      executed hand movements that did not reorient the stimuli. Interference was
      observed only when axes of manual and mental rotation coincided in space.
      Regardless of the hand used, concordant rotational directions facilitated,
      whereas discordant directions inhibited, mental rotation. The results suggest
      that mental object rotation and rotatory object manipulation share a common
      process that is thought to control he dynamics of both imagined and actually
      performed object reorientation.

PMID- 9606109
TI  - Effects of orientation on the identification of rotated objects depend on the
      level of identity.
AB  - Matching names and rotated line drawings of objects showed effects of object
      orientation that depended on name level. Large effects, in the same range as
      object naming, were found for rotations between 0 degrees and 120 degrees from
      upright with subordinate names (e.g., collie), whereas nonsignificant effects
      were found with superordinate (e.g., animal) and basic names (e.g., dog). These
      results support image normalization, after contact with orientation-invariant
      representations, that provide basic-level identity. They consequently fail to
      support theories of object recognition in which rotated object images are
      normalized to the upright position before contact with long-term object
      representations.

PMID- 9606110
TI  - Proceedings of the Association of British Neurologists. London, United Kingdom,
      22-24 October 1997. Abstracts.

PMID- 9606111
TI  - Research: Must it polarize us?

PMID- 9606112
TI  - Cutaneous leishmaniasis in a 6-month-old girl.

PMID- 9606113
TI  - Autolymphocyte therapy. III. Effective adjuvant adoptive cellular therapy with in
      vivo anti-tumor specificity against murine melanoma and carcinoma using ex-vivo
      activated memory T-lymphocytes.

PMID- 9606114
TI  - Crohn's and colitis: recruiting for genetic testing.

PMID- 9606115
TI  - Festschrift for Joel D. Kopple on the occasion of his 60th birthday.

PMID- 9606116
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 17-1998. A 53-year-old man with left ventricular dysfunction four
      years after a heart transplantation.

PMID- 9606117
TI  - Walking and mortality in older men.

PMID- 9606118
TI  - Walking and mortality in older men.

PMID- 9606119
TI  - More on low-fat diets.

PMID- 9606120
TI  - Polymorphism of the cholesteryl ester transfer protein gene.

PMID- 9606121
TI  - Polymorphism of the cholesteryl ester transfer protein gene.

PMID- 9606122
TI  - Genetic polymorphisms and disease.

PMID- 9606123
TI  - Acid-base disorders.

PMID- 9606124
TI  - Acid-base disorders.

PMID- 9606125
TI  - Acid-base disorders.

PMID- 9606126
TI  - Acid-base disorders.

PMID- 9606127
TI  - Underreporting of Lyme disease.

PMID- 9606128
TI  - Corneal ulcers from contact lenses during travel to remote areas.

PMID- 9606129
TI  - Francois Reubi (1917-1997).

PMID- 9606130
TI  - Sequence analysis of the primer binding site (PBS) region of the RNA genome of
      simian and human immunodeficiency viruses (SIV and HIV)

PMID- 9606131
TI  - Prediction of homology and divergence in the secondary structure of polypeptides.
AB  - A quantitative procedure is described for the comparison of secondary structure
      of homologous proteins. Standard predictive methods are used to generate
      probability profiles from pairs of homologous amino acid sequences; correlation
      coefficients (R) are then computed between each pair of amino acids for alpha
      helix (R alpha), extended structure (R beta), turn (R(t)), and coil (R(c)). R
      values are >0.2 for correctly aligned homologous sequences. Unrelated or
      incorrectly aligned sequences give R values near zero. Lack of correlation for a
      segment of otherwise well-correlated sequences is used to identify structural
      divergence, which is then evaluated graphically by using difference profiles. A
      combination of these techniques correctly predicts secondary structural
      differences between melittin or beta-endorphin and their respective synthetic
      analogs. The method is potentially useful to describe evolutionary changes in
      protein secondary structure as well as in the design of peptide analogs.

PMID- 9606132
TI  - Sexual reproduction and population dynamics: the role of polygyny and demographic
      sex differences.
AB  - Most models of population dynamics do not take sexual reproduction into account
      (i.e., they do not consider the role of males). However, assumptions behind this
      practice--that no demographic sex differences exist and males are always abundant
      enough to fertilize all the females--are usually not justified in natural
      populations. On the contrary, demographic sex differences are common, especially
      in polygynous species. Previous models that consider sexual reproduction report a
      stabilizing effect through mixing of different genotypes, thus suggesting a
      decrease in the propensity for complex of dynamics in sexually reproducing
      populations. Here we show that considering the direct role of males in
      reproduction and density dependence leads to the conclusion that a two-sex model
      is not necessarily more stable compared with the corresponding one-sex model.
      Although solutions exist where sexual reproduction has a stabilizing effect even
      when no genotypic variability is included (primarily when associated with
      monogamy), factors like polygyny, sex differences in survival or density
      dependence, and possible alterations of the primary sex ratio (the Trivers
      Willard mechanism), may enlarge the parametric region of complex dynamics. Sexual
      reproduction therefore does not necessarily increase the stability of population
      dynamics and can have destabilizing effects, at least in species with complicated
      mating systems and sexual dimorphism.

PMID- 9606133
TI  - Analysis of three amphibian populations with quarter-century long time-series.
AB  - Amphibians are in decline in many parts of the world. Long tme-series of
      amphibian populations are necessary to distinguish declines from the often strong
      fluctuations observed in natural populations. Time-series may also help to
      understand the causes of these declines. We analysed 23-28-year long time-series
      of the frog Rana temporaria. Only one of the three studied populations showed a
      negative trend which was probably caused by the introduction of fish. Two
      populations appeared to be density regulated. Rainfall had no obvious effect on
      the population fluctuations. Whereas long-term studies of amphibian populations
      are valuable to document population declines, most are too short to reveal those
      factors that govern population dynamics or cause amphibian populations to
      decline.

PMID- 9606134
TI  - Belgian Working Group on Invasive Cardiology 12th annual scientific sessions. 4-5
      December 1997. Abstracts.

PMID- 9606135
TI  - [Symposium of the Paul-Martini-Stiftung in Connection with the Academy of Science
      on "Disease Models in Drug Research". Mainz, Germany, 28-29 November 1997].

PMID- 9606136
TI  - Use of the single-cell gel electrophoresis assay for the immunofluorescent
      detection of specific DNA damage.
AB  - The single-cell gel electrophoresis assay or comet assay is now a widely used
      method to assess the level of DNA damage in irradiated or chemically modified
      cells. We propose an adaptation of the currently applied protocol, aimed at
      singling out a defined modified base, using an immunodetection approach. After
      the electrophoresis step, the DNA tail moment was measured using ethidium
      bromide. Simultaneously, cyclobutane pyrimidine dimers (CPDs), the targeted
      lesions, were revealed by an indirect immunofluorescence detection using a
      specific monoclonal antibody. The assay was validated on human fibroblasts
      exposed to UVB light. The dose-response curves were established, showing a linear
      increase of the antibody response with the dose between 1000 and 10,000 J/m2. The
      detection limit of the method was 500 J/m2. Digestion of the CPDs, induced at
      3000 J/m2, with T4 endonuclease V led to a marked decrease of the antibody
      response, confirming the specificity of the assay. A preliminary repair
      experiment is reported in which the tail moment of the comets together with the
      antibody response are measured, showing the disappearance of 80% of the antibody
      fixation sites within 48 h.

PMID- 9606137
TI  - Membrane protein proteolysis assayed by fluorescence quenching: assay of O
      sialoglycoprotein endopeptidase.
AB  - The assay of the O-sialoglycoprotein endopeptidase of Pasteurella haemolytica has
      previously used the cleavage of 125I-labeled glycophorin A, measured by SDS-PAGE,
      autoradiography, gel-slicing, and scintillation counting. A new assay is based on
      the increased fluorescence which results from proteolytic cleavage of a
      fluorescence-quenched micellar substrate, 4,4-difluor-5,7-dimethyl-4-bora-3
      alpha, 4 alpha-diaza-s-indacene-3-propionic acid conjugated to glycophorin A
      (BODIPY-FL-glycophorin A). Micellar association of glycophorin A molecules
      results in 97% fluorescence quenching despite a low molar ratio of BODIPY-FL
      glycophorin A. Proteolysis of the membrane protein causes greatly enhanced
      fluorescence which is used for a rapid one-step proteolysis assay. Direct
      monitoring of proteolysis in microcuvettes, or routine assay in microtiter plates
      can be used. Reproducibility is higher than with the radiolabeled substrate and
      the K(m) values for the two substrates are similar. The assay is suitable for the
      O-sialoglycoprotein endopeptidase activity of chromatographically purified enzyme
      or unpurified bacterial culture supernatants and can be used to monitor
      inhibition of the O-sialoglycoprotein endopeptidase by neutralizing antibodies.
      The O-sialoglycoprotein endopeptidase assay employing BODIPY-FL-glycophorin A
      provides a rapid and nonradioactive method for the assay of this highly specific
      enzyme.

PMID- 9606138
TI  - Structural analysis of O-linked oligosaccharide-alditols by electrospray-tandem
      mass spectrometry after mild periodate oxidation and derivatization with 2
      aminopyridine.
AB  - O-linked oligosaccharide-alditols were analyzed by a combination of high
      performance liquid chromatography (HPLC) and electrospray-tandem mass
      spectrometry (ESI-MS/MS). First, oligosaccharide-alditols were treated with
      sodium meta-periodate under conditions where core N-acetylgalactosaminitol is
      specifically degraded. The resulting fragments were labeled with 2-aminopyridine
      and purified on a reversed-phase column. Pyridylamino oligosaccharides yielded
      protonated molecular ions in positive-ion ES-MS and gave Y-series sequence ions,
      arising from glycosidic cleavages, by ESI-tandem mass spectrometry. Information
      on sugar sequence and branching of oligosaccharides linked at C6 and C3 to the N
      acetylgalactosaminitol can be obtained. A systematic study of various
      oligosaccharide-alditols demonstrated that this approach constitutes a powerful
      tool for the structural characterization of O-glycans available only in limited
      quantities.

PMID- 9606139
TI  - Detailed characterization of carbohydrate linkage and sequence in an ion trap
      mass spectrometer: glycosphingolipids.
AB  - Electrospray ionization with a quadrupole ion trap (qIT) mass analyzer has been
      utilized to ascertain structural detail obtained with glycoconjugate samples. In
      this report, an isomeric disialyl glycosphingolipid sample extracted from human
      brain tissue was evaluated for sequence, branching, and linkage information.
      Results were obtained that were qualitatively comparable with triple-quadrupole
      instruments (Q1q2Q3) with major carbohydrate fragments from C1-O glycosidic
      rupture and additional fragments that provided a determination of sphingosine and
      N-acyl heterogeneity of the ceramide moiety. In unique contrast, however, the qIT
      extended carbohydrate understanding through multistep mass spectrometric (MSn)
      studies providing for the first time pyran cross-ring cleavages that define the
      interresidue linkage structure for glycolipids. This was achieved by selecting
      secondary fragments (MS2) free from the energy sinks of facile bond rupture that
      dominate product ion spectra. Isolation and activation of these substructures
      result in a more uniform distribution of fragments, providing structural insights
      previously inaccessible by tandem mass spectrometry.

PMID- 9606140
TI  - Immobilization of DNA in polyacrylamide gel for the manufacture of DNA and DNA
      oligonucleotide microchips.
AB  - Activated DNA was immobilized in aldehyde-containing polyacrylamide gel for use
      in manufacturing the MAGIChip (microarrays of gel-immobilized compounds on a
      chip). First, abasic sites were generated in DNA by partial acidic depurination.
      Amino groups were then introduced into the abasic sites by reaction with
      ethylenediamine and reduction of the aldimine bonds formed. It was found that DNA
      could be fragmented at the site of amino group incorporation or preserved mostly
      unfragmented. In similar reactions, both amino-DNA and amino-oligonucleotides
      were attached through their amines to polyacrylamide gel derivatized with
      aldehyde groups. Single- and double-stranded DNA of 40 to 972 nucleotides or base
      pairs were immobilized on the gel pads to manufacture a DNA microchip. The
      microchip was hybridized with fluorescently labeled DNA-specific oligonucleotide
      probes. This procedure for immobilization of amino compounds was used to
      manufacture MAGIChips containing both DNA and oligonucleotides.

PMID- 9606141
TI  - Proteinase K digestion of proteins improves detection of bacterial endotoxins by
      the Limulus amebocyte lysate assay: application for endotoxin removal from
      cationic proteins.
AB  - Cationic proteins, such as lysozyme, ribonuclease A, and human IgG, impaired the
      detection of endotoxins with the Limulus amebocyte lysate assay (LAL assay)
      through formation of endotoxin-protein complexes, demonstrating pronounced
      masking of endotoxins. Methods, such as phenol extraction, dilution heating, and
      perchloric acid treatment failed to demask the endotoxins. Also, digestion with
      trypsin, chymotrypsin, or pronase recovered only 10 to 20% of the applied
      endotoxins. However, endotoxin recoveries up to 100% were obtained with
      proteinase K digestion of the samples prior to the LAL assay. This method was
      then applied to examine the impact of endotoxin masking on endotoxin removal from
      protein solutions by selective adsorption on membrane adsorbers. It was found
      that poly-L-lysine and poly(ethyleneimine) as endotoxin-selective ligands were
      able to pull endotoxins off the proteins studied, thereby guaranteeing successful
      decontamination.

PMID- 9606142
TI  - Rapid determination of molar mass in modified Archibald experiments using direct
      fitting of the Lamm equation.
AB  - A new method is described that allows measurement of the molar mass of the solute
      within 15 to 30 min after start of a conventional long-column sedimentation
      equilibrium experiment. A series of scans of the concentration distribution in
      close vicinity of the meniscus, taken in rapid succession after the start of the
      centrifuge run, is analyzed by direct fitting using the Lamm equation and the
      Svedberg equation. In case of a single solute, this analysis of the initial
      depletion at the meniscus reveals its buoyant molar mass and sedimentation
      coefficient with an accuracy of approximately 10% and provides gross information
      about sample heterogeneity. This method can be used to study macromolecules that
      do not possess the prolonged stability needed in conventional sedimentation
      equilibrium experiments and it can increase the efficiency of sedimentation
      equilibrium experiments of previously uncharacterized samples.

PMID- 9606143
TI  - Tandem immobilized metal-ion affinity chromatography/immunoaffinity purification
      of His-tagged proteins--evaluation of two anti-His-tag monoclonal antibodies.
AB  - A tag comprising four to six histidines genetically fused to the protein of
      interest (His-tag) has been widely used to purify proteins by immobilized metal
      ion affinity chromatography (IMAC). Here we report the utilization of the same
      tag twice in series, first for IMAC and subsequently for immunoaffinity
      purification. Both steps are based on completely different physical principles
      and can therefore remove different contaminants. Two anti-His-tag antibodies (3D5
      and PentaHis) were characterized for their binding and elution properties using
      the BIAcore surface plasmon resonance biosensor. The dissociation constant of the
      PentaHis antibody was determined to be 1 x 10(-8) M and for the 3D5 antibody 3.4
      x 10(-7) M at pH 7.4. Imidazole in the sample did interfere with binding, whereas
      chelating agents such as EDTA and high salt did not. The antibody 3D5 was coupled
      to a column matrix and used for a coupled two-step purification, in which the
      IMAC column is eluted with EDTA and the eluent is loaded directly on the
      immunoaffinity column. This method may constitute a very general procedure to
      purify proteins to near homogeneity without the need to tailor conditions
      individually, and it may thus be very attractive for high-throughput screening
      programs and for developing general protocols for clinical grade material.

PMID- 9606144
TI  - A sensitive equilibrium-based assay for D-lactate using D-lactate dehydrogenase:
      application to penicillin-binding protein/DD-carboxypeptidase activity assays.
AB  - An assay for D-lactate (D-Lac) is described where D-Lac in the presence of NAD+
      is equilibrated to NADH and pyruvate (Pyr) by Leuconostoc mesenteroides D-lactate
      dehydrogenase (DLDH). This assay was standardized using known concentrations of D
      Lac and a linearized form of the equilibrium expression. The assay has a lower
      limit of about 20 microM D-Lac in a 1 ml assay mixture (20 nmol D-Lac). As a
      demonstration of this assay method it is used to characterize the hydrolysis of
      the standard penicillin-binding protein/DD-carboxypeptidase substrate Ac2-L-Lys-D
      Ala-D-Lac by penicillin-binding protein 5 from Escherichia coli. The approach
      adopted here of using an inherently nonlinear response, which however follows
      precisely determinable physical behavior, has the advantages of providing a wider
      dynamic range and increased relative precision over analogous linear response
      based methods. This approach may be applicable to the development of other enzyme
      based assay methods.

PMID- 9606146
TI  - Electrochemical immunoassay based on catalytic conversion of substrate by labeled
      metal ion and polarographic detection of the product generated.
AB  - In a new electrochemical immunoassay based on the conversion of a substrate
      catalyzed by a labeled metal ion and the polarographic detection of the product
      generated, metal copper ion was used to label model antigen human serum albumin
      through the bifunctional chelating agent diethylenetriaminepentaacetic acid.
      After heterogeneous competitive immunoreaction, the labeled copper ion was
      released or activated by acidification and chemically catalyzed the conversion of
      the substrate o-phenylenediamine to the electroactive product 2,3
      diaminophenazine (DAP). The DAP was quantified using linear-potential scan
      polarography. The sensitivity of the proposed assay was 100 times higher than
      that of the previous methods based on direct detection of the metal ion labels.
      This immunoassay can be used to detect any protein of interest.

PMID- 9606145
TI  - Strep-tag II affinity purification: an approach to study intermediates of
      metalloenzyme biosynthesis.
AB  - Complex metalloenzymes (e.g., nitrogenase, hydrogenase, urease) are synthesized
      starting from the apoprotein via several intermediates by the action of accessory
      proteins. The isolation and biochemical characterization of such intermediates is
      hampered by their low abundance and their lability. Here we describe a technique
      for efficient single-step purification of a hydrogenase precursor under mild
      conditions using a N-terminal Strep-tag II affinity peptide and a novel
      StrepTactin Sepharose matrix. The tag was fused to the large subunit of [NiFe]
      hydrogenase 3 (HycE) of Escherichia coli. No significant influence of the
      affinity peptide on maturation or activity of the protein was observed when the
      modified gene was integrated into the chromosome by homologous recombination. A
      tagged nickel-free precursor form of HycE bound quantitatively to a recombinant
      StrepTactin Sepharose column. More than 90% pure subunit could be obtained after
      elution with desthiobiotin. The procedure was shown to be more efficient than
      purification by immobilized metal affinity chromatography using a N-terminal His
      tag. General advantages of the novel Strep-tag II affinity purification
      especially for applications with metalloenzymes are discussed.

PMID- 9606147
TI  - A quantitative study of optical mapping surfaces by atomic force microscopy and
      restriction endonuclease digestion assays.
AB  - Many new techniques in biomolecular chemistry and genomic analysis require the
      immobilization of molecular reagents on specially prepared surfaces. However, the
      process of molecular fixation often interferes with or precludes the use of
      standard in vitro biochemical assays. Optical mapping is an emergent technology
      for genomic analysis which relies on the biochemical activity of DNA fixed to
      silanized glass surfaces. Optical mapping surfaces have been shown to be
      compatible with restriction endonucleases and a variety of DNA polymerases. The
      essential properties of biochemically active surfaces are poorly understood in
      most of the current technologies which utilize molecular fixation, including
      optical mapping. The purpose of this study is to use the powerful technique of
      atomic force microscopy, in combination with informative enzymatic assays, to
      correlate biochemical activity with microscopic surface structure. The results
      presented provide meaningful insight into the effect of surface preparation on
      the biochemical accessibility of surface-bound molecules. Novel analysis which
      may facilitate the automation of optical mapping is presented.

PMID- 9606148
TI  - Lysophosphatidylglycerol: a novel effective detergent for solubilizing and
      purifying the cystic fibrosis transmembrane conductance regulator.
AB  - Similar to the recombinant cystic fibrosis transmembrane conductance regulator
      (CFTR) expressed in Sf9 insect cells, underglycosylated CFTR expressed in yeast
      is not effectively solubilized by a variety of commonly used detergents,
      requiring instead harsh alkali and SDS treatments, which would denature most
      proteins. Moreover, solubilized CFTR has a strong tendency to aggregate and form
      high-molecular-weight aggregates during subsequent purification. We report here
      that the mild detergent, lysophosphatidylglycerol (LPG), is a very effective
      detergent for solubilizing the CFTR expressed in both yeast and Sf9 insect cells.
      LPG solubilizes nearly 100% of the CFTR in yeast in the absence of NaCl and none
      in the presence of 1 M NaCl. It is also very potent in preventing aggregation of
      the CFTR during subsequent purification. Exploiting these characteristics, a
      rapid simple procedure for the purification of functional recombinant CFTR
      expressed in yeast has been developed. It includes selective CFTR solubilization
      in the presence and the absence of NaCl followed by nickel-chelate chromatography
      of His-tagged CFTR. The CFTR produced by this procedure is about 70% pure.
      Purified CFTR molecules were reconstituted into liposomes and then fused to
      planar lipid bilayers for single-channel recording. The reconstituted CFTR
      exhibits regulatory chloride channel activities with a slope conductance of 7.1
      pS and a reversal potential of -32 mV. The effectiveness and simplicity of this
      new purification procedure for the CFTR should greatly facilitate a variety of
      biochemical and biophysical studies of this important protein. Furthermore, the
      potency of LPG in solubilizing the notoriously intractable underglycosylated CFTR
      suggest that this detergent may be useful for solubilizing the CFTR from other
      sources and for other difficult membrane proteins as well.

PMID- 9606149
TI  - Nitrosothiol quantification in human plasma.
AB  - A high-pressure liquid chromatography (HPLC) assay for measuring picomole
      quantities of nitrosothiol in biological samples was developed. The assay
      utilizes the catalytic reduction of nitrosothiol by mercuric cation (Hg2+).
      Released nitrogen oxide reacts with sulfanilamide (SA) and N-(1
      napthyl)ethylenediamine (NNED) to form a stable azo dye. The azo dye is then
      separated from N-(1-napthyl)ethylenediamine and quantified by reversed-phase
      HPLC. In addition to nitrosothiol, nitrite and atmospheric nitrogen oxides are
      sources of nitrogen oxide that react with the reagents, SA and NNED, to form the
      azo dye. Therefore, a reference sample, which includes the nitrosothiol sample
      and all reagents except Hg2+, is utilized for the subtraction of nitrite and
      atmospheric nitrogen oxides which "contaminate" the nitrosothiol sample and
      reagents. This method is a sensitive (approximately 3 pmol; approximately 10(-1)
      microM) and accurate means to measure nitrosothiol concentration in biologic
      samples.

PMID- 9606150
TI  - A quantitative model for using acridine orange as a transmembrane pH gradient
      probe.
AB  - Monitoring the acidification of the internal space of membrane vesicles by proton
      pumps can be achieved easily with optical probes. Transmembrane pH gradients
      cause a blue-shift in the absorbance spectrum and the quenching of the
      fluorescence of the cationic dye acridine orange. It has been postulated that
      these changes are caused by accumulation and aggregation of the dye inside the
      vesicles. We tested this hypothesis using liposomes with transmembrane
      concentration gradients of ammonium sulfate as model system. Fluorescence
      intensity of acridine orange solutions incubated with liposomes was affected by
      magnitude of the gradient, volume trapped by vesicles, and temperature. These
      experimental data were compared to a theoretical model describing the
      accumulation of acridine orange monomers in the vesicles according to the inside
      to-outside ratio of proton concentrations, and the intravesicular formation of
      sandwich-like piles of acridine orange cations. This theoretical model predicted
      quantitatively the relationship between the transmembrane pH gradients and
      spectral changes of acridine orange. Therefore, adequate characterization of
      aggregation of dye in the lumen of biological vesicles provides the theoretical
      basis for using acridine orange as an optical probe to quantify transmembrane pH
      gradients.

PMID- 9606151
TI  - Real-time homogeneous assay of rapid cycle polymerase chain reaction product for
      identification of Leptonema illini.
AB  - Partial 16S rDNA sequences of eight Leptospira-like field isolates that reacted
      weakly or not at all to microscope agglutination test were found to be similar to
      the 16S rDNA sequence of the nonpathogen Leptonema illini-type strain 3055.
      Comparison of these sequences with those of Leptospira 16S rDNA sequences
      revealed a Leptonema species signature sequence for which a forward amplification
      primer was designed. This primer was used in conjunction with a bacterial
      specific 16S rDNA universal reverse primer for developing a LightCycler-based
      rapid PCR protocol in which fluorescence emission due to the binding of SYBR
      green I dye to the amplified products was continuously monitored. A melting
      temperature (T(m)) determined from the melting curve of the amplified product
      immediately after PCR confirmed that the product was of Leptonema. The protocol
      for 24 samples consisting of 30 PCR cycles and melting curve acquisitions
      required 30 min to complete and agarose gel electrophoresis of the PCR products
      was not necessary. The method was specific as PCR products were detected from the
      seven Leptonema reference strains and the eight field isolates that had been
      previously verified as Leptonema by 16S rDNA sequencing, but not from the two
      representative strains from each of the eight Leptospira genospecies tested.

PMID- 9606152
TI  - 4-Hydroxyanisole: the most suitable monophenolic substrate for determining
      spectrophotometrically the monophenolase activity of polyphenol oxidase from
      fruits and vegetables.
AB  - A continuous spectrophotometric method for determining the monophenolase activity
      of polyphenol oxidase from several plant sources is described. This assay method
      is based on the coupling reaction between 3-methyl-2-benzothiazolinone hydrazone
      and the quinone product of the oxidation of 4-hydroxyanisole in the presence of
      polyphenol oxidase. 4-Hydroxyanisole proved to be the best monophenol assayed to
      measure the monophenolase activity of polyphenol oxidase from apple, artichoke,
      avocado, medlar, pear, and strawberry. Kinetic constants of 4-hydroxyanisole were
      compared to those of p-hydroxyphenyl propionic acid, a very sensitive monophenol
      previously reported to assay the monophenolase activity of polyphenol oxidase
      from apple, pear, and mushroom. The high values of the maximum steady state rate
      obtained for 4-hydroxyanisole suggest the existence of high catalytic constant
      toward this monophenol. These kinetic values were supported by nuclear magnetic
      resonance assays which predicted the highest reactivity of 4-hydroxyanisole.
      Therefore nuclear magnetic resonance assays proved to be a valuable and useful
      tool to predict the best monophenolic substrate for plant polyphenol oxidases.
      The 3-methyl-2-benzothiazlolinone-adduct for 4-hydroxyanisole was stable, with
      high molar absorptivity at the optimum pHs of the polyphenol oxidases assayed.
      All this together makes the use of 4-hydroxyanisol as monophenolic substrate and
      3-methyl-2-benzothiazolinone as coupling reagent the most sensitive and precise
      assay method up to date reported in the literature to determine the monophenolas
      activity of polyphenol oxidase from fruits and vegetables.

PMID- 9606153
TI  - Isotope dilution mass spectrometric quantification of 3-nitrotyrosine in proteins
      and tissues is facilitated by reduction to 3-aminotyrosine.
AB  - Oxidative damage by reactive nitrogen species has been implicated in the
      pathogenesis of atherosclerosis and other inflammatory diseases. The mechanisms
      of tissue damage are poorly understood, however, because the toxic intermediates
      are short-lived. Previous in vitro studies have suggested that 3-nitrotyrosine
      represents a specific marker of protein oxidation by reactive nitrogen species.
      The detection of this nitrated aromatic amino acid may thus serve as an indicator
      of tissue injury by nitrogen species in vivo. Here we describe a highly sensitive
      and specific analytical method for quantifying free and protein-bound 3
      nitrotyrosine. The assay involves acid hydrolysis of proteins, isolation of 3
      nitrotyrosine by ion exchange chromatography, and reduction of 3-nitrotyrosine to
      3-aminotyrosine with dithionite. The reduced amino acid is then converted to its
      n-propyl, per-heptafluorobutyryl derivative and quantified by isotope dilution
      gas chromatography negative-ion chemical ionization mass spectrometry. Attomole
      levels of 3-nitrotyrosine can be reproducibly measured in this manner.
      Quantifying 3-nitrotyrosine levels of tissues by stable isotope dilution gas
      chromatography/mass spectrometry should provide a powerful tool for exploring the
      impact of reactive nitrogen species on oxidative reactions in vivo.

PMID- 9606154
TI  - Protein structure in KBr pellets by infrared spectroscopy.
AB  - In this work we analyzed the secondary structure of 13 globular proteins in KBr
      pellet through Fourier transform infrared spectroscopy (FTIR). The quantification
      was based in singular value decomposition (SVD) theory, a pattern recognition
      method. The results show better correlation for alpha helix (0.90) and beta sheet
      (0.84) in amide I band, similar to the results obtained for proteins in solution.
      These results show that the protein secondary structure is conserved in solid
      state, in opposition to the results observed by FTIR using resolution enhancement
      techniques. The SVD analysis also show that in KBr pellets the protein secondary
      structures have absorbances in different wavenumbers when compared to those in
      solution. In this way, the use of KBr pellet and the pattern recognition method
      can be an ideal method to analyze protein secondary structure by FTIR.

PMID- 9606155
TI  - Employment of a phenoxy-substituted acridinium ester as a long-lived
      chemiluminescent indicator of glucose oxidase activity and its application in an
      alkaline phosphatase amplification cascade immunoassay.
AB  - This paper describes the employment of a novel phenoxy-substituted acridinium
      ester (di-ortho-bromophenyl-AE) as a chemiluminescent endpoint indicator for
      ligand binding assays. The reactivity of this compound is such that it is capable
      of generating a high-intensity chemiluminescent signal at neutral pH. Under these
      conditions, when present in excess, it has been used as an indicator of hydrogen
      peroxide generation by the action of glucose oxidase (GOx, EC 1.1.3.4) on glucose
      substrate. The resulting chemiluminescent signal is a long-lived glow. The
      magnitude of the chemiluminescent signal is directly proportional to the quantity
      of GOx present and has been used to measure GOx with a sensitivity of 1.8 x 10(
      16) mol. In addition, this ability to monitor GOx activity has been utilized in
      an alkaline phosphatase (ALP, EC 3.1.3.1) amplification cascade assay. Here ALP
      catalyzes the formation of FAD from a prosthetogenic substrate FADP. FAD, a
      cofactor for a number of oxidase enzymes, then converts inactive apo-GOx to holo
      GOx, the activity of which is monitored by the chemiluminescent endpoint and
      facilitates detection of ALP over the range 10(-15) to 4.1 x 10(-19) mol. The
      clinical utility of this system has been demonstrated by application to the assay
      of human thyrotrophin (TSH, sensitivity 0.005 mU/liter).

PMID- 9606156
TI  - Selective detection of lactolated peptides in hydrolysates by liquid
      chromatography/electrospray tandem mass spectrometry.
AB  - In food processing as well as in human nutrition and physiology, the increasing
      importance of the Maillard reaction has brought about the need for analytical
      means to detect and characterize the protein-bound Amadori products. In this
      paper, we describe a highly selective and sensitive method for detecting peptides
      glycated with lactose (lactolated peptides) from a complex hydrolysate using
      electrospray ionization tandem mass spectrometry. Protonated molecular ions of
      lactolated peptides gave a product-ion spectrum, with the dominant mode of
      decomposition including cleavage of the O-glycosidic bond followed by dehydration
      steps giving a characteristic neutral loss of 216 Da. Optimization of the ion
      marker [M + H]+ - 216, identified as a furylium ion, was investigated. It
      remained dominant regardless of the nature of the glycated peptides, the
      collision energy used, or the charge state of the parent ion. An approach for
      detecting lactolated peptides from protein digest was proposed during reverse
      phase high-performance liquid chromatography (HPLC)/electrospray mass
      spectrometry and reverse-phase HPLC/tandem mass spectrometry using neutral loss
      scanning. This technique detected picomole amounts of lactolated peptides.

PMID- 9606157
TI  - Elution of lipopolysaccharides from polyacrylamide gels.
AB  - A simple procedure for elution in water of bacterial lipopolysaccharides (LPS)
      from sodium dodecyl sulfate-polyacrylamide gels is described. It consists of the
      combination of three principal steps: first, highly sensitive on-gel LPS
      detection (1-10 ng/band) with zinc-imidazole (negative or reverse staining);
      second, washing of the individual LPS band in a solution of a zinc-complexing
      agent (e.g., 100 mM EDTA); and finally, elution of the LPS (100-200 microliters
      water for a 0.5-microgram LPS band) from gel microparticles for 3 h at room
      temperature. Using this procedure, we have successfully eluted a variety of LPS
      forms from Bordetella pertussis, Escherichia coli 0111:B4, E. coli K-235,
      Salmonella enteritidis, and Pseudomonas aeruginosa. Elution recovery of rough or
      semismooth LPS was about 70-80%, while that of smooth LPS was only about 10%.
      Eluted LPS was biologically active as tested by limulus amebocyte lysate and TNF
      alpha assays.

PMID- 9606158
TI  - William James McGill (1922-1997).
AB  - Copyright

PMID- 9606159
TI  - Generalization of the Theory of Signal Detectability to n-Event m-Dimensional
      Forced-Choice Tasks.
AB  - This paper presents a generalization of the theory of signal detectability to n
      event forced-choice tasks where the evidence can be modelled by an m-dimensional
      vector. The generalization is based on a nonparametric model that encompasses
      decision rules for maximizing the proportion of correct decisions. The model
      assumes that observers identify events by partitioning a decision space of
      dimension n-1 with a template. Translating the template by varying the decisional
      bias yields a set of receiver operating characteristic (ROC) surfaces. Following
      B. K. Scurfield [1996, J. Math. Psych. 40, 253-269], event-discriminability is
      defined by considering the Shannon entropy of the volumes under the ROC surfaces.
      The resultant discriminability measure is interpreted with respect to the random
      vectors assumed to be associated with the decision space and shown to equate with
      the channel capacity of an observer in a multiple-interval forced-choice task.
      Copyright 1998 Academic Press.

PMID- 9606160
TI  - A Measurement of the Certainty Effect.
AB  - In order to measure the certainty effect, the present paper tries to develop an
      axiomatic model of decision under risk which can accommodate the certainty effect
      and is, apart from this property, equivalent to expected utility. This leads to a
      new concept denoted by certainty preference which implies that a higher utility
      index is assigned to a consequence in the case of certainty than to the same
      consequence in the presence of risk. Now, a notion of comparative certainty
      preference can be obtained which will be characterized in terms of properties of
      the derived utility representation and allows for a generalization of the Arrow
      Pratt measure of absolute risk aversion. Copyright 1998 Academic Press.

PMID- 9606161
TI  - Weak Extensive Measurement without Translation-Invariance Axioms.
AB  - A new system of axioms that are necessary and sufficient for weak extensive
      measurement on totally preordered indifference-semigroups is introduced. No axiom
      of translation-invariance is used. Copyright 1998 Academic Press.

PMID- 9606162
TI  - Error Correction Processes in Temporal Pattern Production.
AB  - A second-order autoregressive model for error correction is applied to
      measurements of synchronized tapping by an expert and a nonexpert subject for a
      wide range of patterns, ranging from simple off-beat tapping to a complex
      polyrhythm. The model can be seen as an extension of the first order approach of
      Vorberg and Wing and, also, as a linearized version of a general nonlinear model
      proposed by the author in another publication. The central measured variable is
      the asynchrony between presented tone and produced tap. General relations for the
      asynchrony autocovariance functions are derived, as well as covariance-based
      expressions for first- and second-order autoregressive error correction
      parameters. A second method of error parameter estimation, based on "local"
      binned calculations, is also presented. Combination of the two methods,
      buttressed by simulations, allows effective characterization of the time series'
      order and parameter values, and experimental support for the model is found to be
      strong in all cases. Error correction processes prove to be predominantly first
      order; second (and possibly higher) order effects occur predominantly under
      conditions of expertise and relatively high task demands. Expertise in tapping
      (as determined from these two subjects) is found to lead to reduced bias, reduced
      asynchrony and interonset variance, and, with the exception of a single case,
      increased values of error correction parameters relative to untrained
      performance. In a clear majority of cases where it could be tested, both the AR1
      error correction parameter alpha, and the asynchrony and interonset standard
      deviations showed a strong tendency towards a linear relationship with tapping
      period. Copyright 1998 Academic Press.

PMID- 9606164
TI  - TELEGRAPHIC REVIEWS.
AB  - Copyright

PMID- 9606163
TI  - The Choice Probabilities of the Latent-Scale Model Satisfy the Size-Independent
      Model When n Is Small.
AB  - Two probabilistic models for subset choices are compared. The first one, due to
      Marley (1993), was dubbed the latent-scale model by Regenwetter, Marley, and Joe
      (1996). The second one is Falmagne and Regenwetter's (1996) size-independent
      model of approval voting. We show that for up to five choice alternatives, the
      choice probabilities generated by the latent-scale model can be explained also by
      the size-independent model. The proof uses the Konig-Hall theorem of graph theory
      and the characterization of the size-independent model by the approval-voting
      polytope of Doignon and Regenwetter (1997). The problem remains open for the case
      with more than five choice alternatives. Copyright 1998 Academic Press.

PMID- 9606167
TI  - RECENTLY ACCEPTED MANUSCRIPTS.
AB  - Copyright

PMID- 9606166
TI  - 31st Annual Meeting of the Society for Mathematical Psychology.
AB  - Copyright

PMID- 9606168
TI  - Anger and Gender Effects in Observed Supervisor-Subordinate Dyadic Interactions.
AB  - This study investigates the effects of a supervisor's anger and supervisor's and
      subordinate's gender on evaluations made by observers of interacting supervisor
      subordinate dyads. In a laboratory experiment, 370 undergraduates viewed one of
      eight video-tapes representing the conditions of the 2 (gender of supervisor) x 2
      (gender of subordinate) x 2 (presence or absence of anger) design and then
      completed evaluations of the supervisor and the subordinate. A field study using
      265 employees from three organizations replicated the laboratory results. In
      spite of constant dialogue in the interactions across all eight conditions,
      supervisors expressing anger were rated lower and female supervisors were rated
      higher by observers. Subordinates were rated higher when interacting with an
      angry supervisor and when interacting with a male supervisor. Main effects of
      supervisor's gender may reflect over-evaluation of unexpected, albeit average,
      performance. The joint supervisor and subordinate effects are interpreted as
      reflecting a dyadic rating effect in which high ratings assigned to one member of
      the dyad are accompanied by lower ratings assigned to the other member. Copyright
      1997 Academic Press.

PMID- 9606169
TI  - Toward an Explanation of Applicant Reactions: An Examination of Organizational
      Justice and Attribution Frameworks.
AB  - This study used the organizational justice and attribution theory frameworks to
      understand the processes by which applicants perceive and react to selection
      procedures and decisions. Actual applicants were studied at two stages in a
      selection process (i.e., pre-application and post-offer). Interactions between
      process and outcome fairness were observed for intentions (recommendation and
      reapplication) and self-assessed performance. Although the form of the
      interaction was specific to each measure, in general fair procedures resulted in
      more favorable perceptions, and this become more pronounced when individuals also
      perceived fair outcomes. An interaction was also observed for process fairness
      and the actual selection decision; self-efficacy was lowest for those who were
      selected and perceived unfair procedures. The causal attributions for the
      selection decision were related to intentions and self-perceptions, and
      applicants demonstrated self-serving biases, but only when procedures were
      perceived as fair. Potential links between the organizational justice and
      attribution frameworks were also examined. Both frameworks were found to provide
      insight into the psychological processes that influence applicants' intentions
      and self-perceptions. Copyright 1997 Academic Press.

PMID- 9606170
TI  - When the Going Gets Tough, Do the Tough Ask for Help? Help Seeking and Power
      Motivation in Organizations.
AB  - Individuals do not seek help, even when help is needed and available, because
      help seeking implies incompetence and dependence, and therefore is related to
      powerlessness. It was hypothesized that gender, status, and organizational norms
      affect the importance of maintaining and accruing power, which in turn affect
      help seeking behaviors. A laboratory and a field study showed that there was more
      help seeking between equal-status than unequal-status individuals. Further, both
      studies revealed that males sought more help in collective than individualistic
      organizational norms, though the trend was not apparent for females. These
      results shed light on the psychological mechanisms underlying help seeking
      behaviors and have practical implications for developing steps to foster help
      seeking in organizations. Copyright 1997 Academic Press.

PMID- 9606171
TI  - Negotiation Teamwork: The Impact of Information Distribution and Accountability
      on Performance Depends on the Relationship among Team Members.
AB  - We examined how the distribution of information among team members and
      accountability pressures affected the quality of negotiated settlements reached
      among teams of friends negotiating against teams of strangers. The main
      conclusions of the experiment may be summarized by the following findings: (1)
      Teams of strangers reaped a greater share of the joint profit than did teams of
      friends when teammates were accountable to a supervisor as opposed to negotiating
      strictly on their own behalf. (2) Teams of strangers also reaped a marginally
      greater share of the joint profit than did teams of friends when teammates
      possessed unique, as opposed to common, information about their own team's
      preferences. (3) Not surprisingly, teams of friends were more cohesive than were
      teams of strangers; however, teams of friends were also more concerned about
      maintaining their relationship than were teams of strangers. (4) Teams of friends
      felt least cohesive when they were accountable to a supervisor, whereas teams of
      strangers felt most cohesive when they were accountable. Similarly, friends
      indicated greater relationship concerns when having to deal with distributed
      information, whereas information distribution had no effect on the relationship
      concerns of strangers. (5) For teams of strangers, greater team cohesiveness was
      positively correlated with better performance. (6) Moreover, when teams of
      strangers felt more cohesive than their opponents, they earned more than teams of
      strangers who felt less cohesive. Copyright 1997 Academic Press.

PMID- 9606172
TI  - Groups and Solos in Context: The Effects of Accountability on Team Negotiation.
AB  - This study examines whether and how accountability to constituents affects the
      cognitions, performance, and outcomes of team and solo negotiators. Previous
      findings for solos were replicated here: solo negotiators respond competitively
      when they are accountable to constituents. For teams, however, accountability
      pressures were distributed across the members resulting in each team member
      experiencing little responsibility for outcomes. As a consequence, teams did not
      respond to accountability pressures by behaving contentiously as solos did.
      Analysis of negotiators' perceptions of advantage reveals that solos who
      negotiate under conditions of high accountability consider themselves to be at a
      disadvantage in the negotiation even before the negotiation begins. These
      perceptions may underlie the accountability/competitive relation that
      characterizes solo negotiation. Implications for negotiation research as well as
      the study of groups in organizations are discussed. Copyright 1997 Academic
      Press.

PMID- 9606173
TI  - The Jackson Laboratory.

PMID- 9606174
TI  - Cell cycle exit: growth arrest, apoptosis, and tumor suppression revisited.

PMID- 9606175
TI  - MIF expression in the rat brain: implications for neuronal function.
AB  - BACKGROUND: The mediator known historically as macrophage migration inhibitory
      factor (MIF) has been identified recently as being released into the circulation
      by the anterior pituitary gland as a consequence of stress or during a systemic
      inflammatory response. Macrophages and T cells also secrete MIF, both in response
      to proinflammatory factors or upon stimulation with glucocorticoids. Once
      released, MIF "overrides" or counterregulates the immunosuppressive effects of
      steroids on cytokine production and immune cellular activation. To further
      investigate the biology of MIF and its role in the neuroendocrine system, we have
      studied the regional and cellular expression of MIF in brain tissue obtained from
      normal rats and rats administered LPS intracisternally. MATERIALS AND METHODS:
      Rat brain sections were analyzed by immunohistochemistry utilizing an affinity
      purified, anti-MIF antibody raised to recombinant MIF, and by in situ
      hybridization using a digoxigenin-labeled, antisense MIF cRNA probe. The kinetics
      of MIF mRNA expression in brain were compared with that of IL-1, IL-6, and TNF
      alpha by RT-PCR of total brain RNA. The cerebrospinal fluid content of MIF and
      TNF-alpha proteins was analyzed by Western blotting and ELISA. RESULTS: A strong
      baseline expression pattern for MIF was observed in neurons of the cortex,
      hypothalamus, hippocampus, cerebellum, and pons. By in situ hybridization, MIF
      mRNA was found predominantly in cell bodies whereas MIF protein was detected
      mostly within the terminal fields associated with neurons. There was a marked
      pattern of MIF immunoreactivity within the mossy fibers of the dentate gyrus and
      dendrites of the hippocampal CA3 field. These structures have been shown
      previously to be involved in glucocorticoid-induced tissue damage within the
      hippocampus, suggesting an association between MIF and targets of glucocorticoid
      action. The intracisternal injection of LPS increased MIF mRNA and protein
      expression in brain and MIF immunoreactivity was due in part to infiltrating
      monocytes/macrophages. MIF protein also was found to be rapidly released into the
      cerebrospinal fluid. This response corresponded with that of LPS-induced cytokine
      release and MIF mRNA expression increased in a distribution that colocalized in
      large part with that of TNF-alpha, IL-1 beta, and IL-6. CONCLUSION: The
      significant levels of baseline and inducible MIF expression in the brain and its
      regional association with glucocorticoid action underscore the importance of this
      mediator as a physiological regulator of the inflammatory stress response and
      further define its role within the neuroendocrine system.

PMID- 9606176
TI  - T-cell epitopes in type 1 diabetes autoantigen tyrosine phosphatase IA-2:
      potential for mimicry with rotavirus and other environmental agents.
AB  - The tyrosine phosphatase IA-2 is a molecular target of pancreatic islet
      autoimmunity in type 1 diabetes. T-cell epitope peptides in autoantigens have
      potential diagnostic and therapeutic applications, and they may hold clues to
      environmental agents with similar sequences that could trigger or exacerbate
      autoimmune disease. We identified 13 epitope peptides in IA-2 by measuring
      peripheral blood T-cell proliferation to 68 overlapping, synthetic peptides
      encompassing the intracytoplasmic domain of IA-2 in six at-risk type 1 diabetes
      relatives selected for HLA susceptibility haplotypes. The dominant epitope,
      VIVMLTPLVEDGVKQC (aa 805-820), which elicited the highest T-cell responses in all
      at-risk relatives, has 56% identity and 100% similarity over 9 amino acids (aa)
      with a sequence in VP7, a major immunogenic protein of human rotavirus. Both
      peptides bind to HLA-DR4(*0401) and are deduced to present identical aa to the T
      cell receptor. The contiguous sequence of VP7 has 75% identity and 92% similarity
      over 12 aa with a known T-cell epitope in glutamic acid decarboxylase (GAD),
      another autoantigen in type 1 diabetes. This dominant IA-2 epitope peptide also
      has 75-45% identity and 88-64% similarity over 8-14 aa to sequences in Dengue,
      cytomegalovirus, measles, hepatitis C, and canine distemper viruses, and the
      bacterium Haemophilus influenzae. Three other IA-2 epitope peptides are 71-100%
      similar over 7-12 aa to herpes, rhino-, hanta- and flaviviruses. Two others are
      80-82% similar over 10-11 aa to sequences in milk, wheat, and bean proteins.
      Further studies should now be carried out to directly test the hypothesis that T
      cell activation by rotavirus and possibly other viruses, and dietary proteins,
      could trigger or exacerbate beta-cell autoimmunity through molecular mimicry with
      IA-2 and (for rotavirus) GAD.

PMID- 9606178
TI  - Na+,K(+)-ATPase phosphorylation in the choroid plexus: synergistic regulation by
      serotonin/protein kinase C and isoproterenol/cAMP-PK/PP-1 pathways.
AB  - BACKGROUND: The ion pump Na+,K(+)-ATPase is responsible for the secretion of
      cerebrospinal fluid from the choroid plexus. In this tissue, the activity of
      Na+,K(+)-ATPase is inhibited by serotonin via stimulation of protein kinase C
      catalyzed phosphorylation. The choroid plexus is highly enriched in two
      phosphoproteins which act as regulators of protein phosphatase-1 activity, DARPP
      32 and inhibitor-1. Phosphorylation catalyzed by cAMP-dependent protein kinase on
      a single threonyl residue converts DARPP-32 and inhibitor-1 into potent
      inhibitors of protein phosphatase-1. Previous work has shown that in the choroid
      plexus, phosphorylation of DARPP-32 and I-1 is enhanced by isoproterenol and
      other agents that activate cAMP-PK. We have now examined the possible involvement
      of the cAMP-PK/protein phosphatase-1 pathway in the regulation of Na+,K(+)
      ATPase. MATERIALS AND METHODS: The state of phosphorylation of Na+,K(+)-ATPase
      was measured by determining the amount of radioactivity incorporated into the ion
      pump following immunoprecipitation from 32P-prelabeled choroid plexuses incubated
      with various drugs (see below). Two-dimensional phosphopeptide mapping was
      employed to identify the protein kinase involved in the phosphorylation of
      Na+,K(+)-ATPase. RESULTS: The serotonin-mediated increase in Na+,K(+)-ATPase
      phosphorylation is potentiated by okadaic acid, an inhibitor of protein
      phosphatases-1 and -2A, as well as by forskolin or the beta-adrenergic agonist,
      isoproterenol, activators of cAMP-dependent protein kinase. Two-dimensional
      phosphopeptide maps suggest that this potentiating action occurs at the level of
      a protein kinase C phosphorylation site. Forskolin and isoproterenol also
      stimulate the phosphorylation of DARPP-32 and protein phosphatase inhibitor-1,
      which in their phosphorylated form are potent inhibitors of protein phosphatase
      1. CONCLUSIONS: The results presented here support a model in which okadaic acid,
      forskolin, and isoproterenol achieve their synergistic effects with serotonin
      through phosphorylation of DARPP-32 and inhibitor-1, inhibition of protein
      phosphatase-1, and a reduction of dephosphorylation of Na+,K(+)-ATPase at a
      protein kinase C phosphorylation site.

PMID- 9606177
TI  - Clonally-related immunoglobulin VH domains and nonrandom use of DH gene segments
      in rheumatoid arthritis synovium.
AB  - BACKGROUND: Synovia of patients with long-standing rheumatoid arthritis (RA) are
      typically infiltrated with B lymphocytes and plasma cells that secrete large
      amounts of immunoglobulin. The CDR3 of an immunoglobulin heavy chain is composed
      of the VH-DH-JH join, with interposed N region addition, and thus defines clonal
      relatedness. Furthermore, the CDR3 lies at the center of the antigen binding
      site, so its length and composition influence antigen binding. We sought
      definitive evidence of an antigen-driven B cell response (i.e., clones derived
      from the same VH, DH, and JH gene segments with shared somatic mutations) in RA
      synovial mRNA transcripts, and to characterize CDR3 intervals at the target of
      inflammation in this autoimmune disease. MATERIALS AND METHODS: We screened a
      cDNA library generated from unselected cells from the knee joint of a 62-year-old
      white female with long-standing RA. This technique does not have the potential
      bias of selecting for antibodies that express a particular reactivity such as
      rheumatoid factor. C gamma recombinants were sequenced and progenitor VH, DH, and
      JH gene segments were assigned and somatic mutations determined by comparison to
      germline sequences. Analyses of DH reading frame utilization and hydropathy
      characteristics of CDR3s were performed. RESULTS: Two of 67 recombinants were
      derived from the same VH (V3-11) and JH gene segments, demonstrated shared
      mutations, and contained nearly identical VH-DH-JH joins, including N region
      addition. Three other recombinants contained identical sequence throughout the
      variable domain. We also found preferential utilization of a limited number of VH
      and DH gene segments and marked preference for a DH reading frame encoding
      predominantly hydrophilic residues. CONCLUSIONS: Analysis of expressed heavy
      chain variable domains strongly supports the hypothesis that the B cell response
      in RA synovium is at least in part antigen driven and oligoclonal.

PMID- 9606179
TI  - Human lung surfactant protein A exists in several different oligomeric states:
      oligomer size distribution varies between patient groups.
AB  - BACKGROUND: Lung surfactant protein A (SP-A) is a complex molecule composed of up
      to 18 polypeptide chains. In vivo, SP-A probably binds to a wide range of inhaled
      materials via the interaction of surface carbohydrates with the lectin domains of
      SP-A and mediates their interaction with cells as part of a natural defense
      system. Multiplicity of lectin domains gives high-affinity binding to
      carbohydrate-bearing surfaces. MATERIALS AND METHODS: Gel filtration analyses
      were performed on bronchoalveolar lavage (BAL) fluid samples from three patient
      groups: pulmonary alveolar proteinosis (n = 12), birch pollen allergy (n = 11),
      and healthy volunteers (n = 4). Sucrose density gradient centrifugation was
      employed to determine molecular weights of SP-A oligomers. SP-A was solubilized
      from the lipid phase to compare oligomeric state with that of water soluble SP-A.
      RESULTS: SP-A exists as fully assembled complexes with 18 polypeptide chains, but
      it is also consistently found in smaller oligomeric forms. This is true for both
      the water- and lipid-soluble fractions of SP-A. CONCLUSION: The three patient
      groups analyzed show a shift towards lower oligomeric forms of SP-A in the
      following sequence: healthy-pulmonary alveolar proteinosis-pollen allergy.
      Depolymerization would be expected to lead to loss of binding affinity for
      carbohydrate-rich surfaces, with loss or alteration of biological function. While
      there are many complex factors involved in the establishment of an allergy, it is
      possible that reduced participation of SP-A in clearing a potential allergen from
      the lungs could be an early step in the chain of events.

PMID- 9606180
TI  - A role for HLA-DO as a co-chaperone of HLA-DM in peptide loading of MHC class II
      molecules.
AB  - In B cells, the non-classical human leukocyte antigens HLA-DO (DO) and HLA-DM
      (DM) are residents of lysosome-like organelles where they form tight complexes.
      DM catalyzes the removal of invariant chain-derived CLIP peptides from classical
      major histocompatibility complex (MHC) class II molecules, chaperones them until
      peptides are available for loading, and functions as a peptide editor. Here we
      show that DO preferentially promotes loading of MHC class II molecules that are
      dependent on the chaperone activity of DM, and influences editing in a positive
      way for some peptides and negatively for others. In acidic compartments, DO is
      engaged in DR-DM-DO complexes whose physiological relevance is indicated by the
      observation that at lysosomal pH DM-DO stabilizes empty class II molecules more
      efficiently than DM alone. Moreover, expression of DO in a melanoma cell line
      favors loading of high-stability peptides. Thus, DO appears to act as a co
      chaperone of DM, thereby controlling the quality of antigenic peptides to be
      presented on the cell surface.

PMID- 9606181
TI  - The Vps4p AAA ATPase regulates membrane association of a Vps protein complex
      required for normal endosome function.
AB  - Vps4p is an AAA-type ATPase required for efficient transport of biosynthetic and
      endocytic cargo from an endosome to the lysosome-like vacuole of Saccharomyces
      cerevisiae. Vps4p mutants that do not bind ATP or are defective in ATP hydrolysis
      were characterized both in vivo and in vitro. The nucleotide-free or ADP-bound
      form of Vps4p existed as a dimer, whereas in the ATP-locked state, Vps4p dimers
      assembled into a decameric complex. This suggests that ATP hydrolysis drives a
      cycle of association and dissociation of Vps4p dimers/decamers. Nucleotide
      binding also regulated the association of Vps4p with an endosomal compartment in
      vivo. This membrane association required the N-terminal coiled-coil motif of
      Vps4p, but deletion of the coiled-coil domain did not affect ATPase activity or
      oligomeric assembly of the protein. Membrane association of two previously
      uncharacterized class E Vps proteins, Vps24p and Vps32p/Snf7p, was also affected
      by mutations in VPS4. Upon inactivation of a temperature-conditional vps4 mutant,
      Vps24p and Vps32p/Snf7p rapidly accumulated in a large membrane-bound complex.
      Immunofluorescence indicated that both proteins function with Vps4p at a common
      endosomal compartment. Together, the data suggest that the Vps4 ATPase catalyzes
      the release (uncoating) of an endosomal membrane-associated class E protein
      complex(es) required for normal morphology and sorting activity of the endosome.

PMID- 9606182
TI  - Interaction and functional cooperation of the leukemia-associated factors AML1
      and p300 in myeloid cell differentiation.
AB  - The AML1 transcription factor and the transcriptional coactivators p300 and CBP
      are the targets of chromosome translocations associated with acute myeloid
      leukemia and myelodysplastic syndrome. In the t(8;21) translocation, the AML1
      (CBFA2/PEBP2alphaB) gene becomes fused to the MTG8 (ETO) gene. We previously
      found that the terminal differentiation step leading to mature neutrophils in
      response to granulocyte colony-stimulating factor (G-CSF) was inhibited by the
      ectopic expression of the AML1-MTG8 fusion protein in L-G murine myeloid
      progenitor cells. We show here that overexpression of normal AML1 proteins
      reverses this inhibition and restores the competence to differentiate.
      Immunoprecipitation analysis shows that p300 and CREB-binding protein (CBP)
      interact with AML1. The C-terminal region of AML1 is responsible for the
      induction of cell differentiation and for the interaction with p300.
      Overexpression of p300 stimulates AML1-dependent transcription and the induction
      of cell differentiation. These results suggest that p300 plays critical roles in
      AML1-dependent transcription during the differentiation of myeloid cells. Thus,
      AML1 and its associated factors p300 and CBFbeta, all of which are targets of
      chromosomal rearrangements in human leukemia, function cooperatively in the
      differentiation of myeloid cells.

PMID- 9606183
TI  - HIF-1 alpha is required for solid tumor formation and embryonic vascularization.
AB  - The transcriptional response to lowered oxygen levels is mediated by the hypoxia
      inducible transcription factor (HIF-1), a heterodimer consisting of the
      constitutively expressed aryl hydrocarbon receptor nuclear translocator (ARNT)
      and the hypoxic response factor HIF-1alpha. To study the role of the
      transcriptional hypoxic response in vivo we have targeted the murine HIF-1alpha
      gene. Loss of HIF-1alpha in embryonic stem (ES) cells dramatically retards solid
      tumor growth; this is correlated with a reduced capacity to release the
      angiogenic factor vascular endothelial growth factor (VEGF) during hypoxia. HIF
      1alpha null mutant embryos exhibit clear morphological differences by embryonic
      day (E) 8.0, and by E8.5 there is a complete lack of cephalic vascularization, a
      reduction in the number of somites, abnormal neural fold formation and a greatly
      increased degree of hypoxia (measured by the nitroimidazole EF5). These data
      demonstrate the essential role of HIF-1alpha in controlling both embryonic and
      tumorigenic responses to variations in microenvironmental oxygenation.

PMID- 9606184
TI  - P2X1 and P2X3 receptors form stable trimers: a novel structural motif of ligand
      gated ion channels.
AB  - P2X receptors are cation channels gated by extracellular ATP. The seven known P2X
      isoforms possess no sequence homology with other proteins. Here we studied the
      quaternary structure of P2X receptors by chemical cross-linking and blue native
      PAGE. P2X1 and P2X3 were N-terminally tagged with six histidine residues to allow
      for non-denaturing receptor isolation from cRNA-injected, [35S]methionine-labeled
      oocytes. The His-tag did not change the electrophysiological properties of the
      P2X1 receptor. His-P2X1 was found to carry four N-glycans per polypeptide chain,
      only one of which acquired Endo H resistance en route to the plasma membrane. 3,
      3'-Dithiobis(sulfosuccinimidylpropionate) (DTSSP) and two of three bifunctional
      analogues of the P2X receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'
      disulfonic acid (PPADS) cross-linked digitonin-solubilized His-P2X1 and His-P2X3
      quantitatively to homo-trimers. Likewise, when analyzed by blue native PAGE, P2X
      receptors purified in digitonin or dodecyl-beta-D-maltoside migrated entirely as
      non-covalently linked homo-trimers, whereas the alpha2 beta gamma delta nicotinic
      acetylcholine receptor (used as a positive control) migrated as the expected
      pentamer. P2X monomers remained undetected soon after synthesis, indicating that
      trimerization occurred in the endoplasmic reticulum. The plasma membrane form of
      His-P2X1 was also identified as a homo-trimer. If n-octylglucoside was used for
      P2X receptor solubilization, homo-hexamers were observed, suggesting that trimers
      can aggregate to form larger complexes. We conclude that trimers represent an
      essential element of P2X receptor structure. KEYWORDS: blue native PAGE/cross
      linking/P2X receptor/quaternary structure.

PMID- 9606185
TI  - Constitutive activation of gastric H+,K+-ATPase by a single mutation.
AB  - In the reaction cycle of P-type ATPases, an acid-stable phosphorylated
      intermediate is formed which is present in an intracellularly located domain of
      the membrane-bound enzymes. In some of these ATPases, such as Na+,K+-ATPase and
      gastric H+, K+-ATPase, extracellular K+ ions stimulate the rate of
      dephosphorylation of this phosphorylated intermediate and so stimulate the ATPase
      activity. The mechanism by which extracellular K+ ions stimulate the
      dephosphorylation process is unresolved. Here we show that three mutants of
      gastric H+,K+-ATPase lacking a negative charge on residue 820, located in
      transmembrane segment six of the alpha-subunit, have a high SCH 28080-sensitive,
      but K+-insensitive ATPase activity. This high activity is caused by an increased
      'spontaneous' rate of dephosphorylation of the phosphorylated intermediate. A
      mutant with an aspartic acid instead of a glutamic acid residue in position 820
      showed hardly any ATPase activity in the absence of K+, but K+ ions stimulated
      ATPase activity and the dephosphorylation process. These findings indicate that
      the negative charge normally present on residue 820 inhibits the
      dephosphorylation process. K+ ions do not stimulate dephosphorylation of the
      phosphorylated intermediate directly, but act by neutralizing the inhibitory
      effect of a negative charge in the membrane.

PMID- 9606186
TI  - The m3 muscarinic acetylcholine receptor differentially regulates calcium influx
      and release through modulation of monovalent cation channels.
AB  - Several types of transmembrane receptors regulate cellular responses through the
      activation of phospholipase C-mediated Ca2+ release from intracellular stores. In
      non-excitable cells, the initial Ca2+ release is typically followed by a
      prolonged Ca2+ influx phase that is important for the regulation of several Ca2+
      sensitive responses. Here we describe an agonist concentration-dependent
      mechanism by which m3 muscarinic acetylcholine receptors (mAChRs) differentially
      regulate the magnitude of the release and influx components of a Ca2+ response.
      In transfected Chinese hamster ovary cells expressing m3 mAChRs, doses of the
      muscarinic agonist carbachol ranging from 100 nM to 1 mM evoked Ca2+ release
      responses of increasing magnitude; maximal Ca2+ release was elicited by the
      highest carbachol concentration. In contrast, Ca2+ influx was maximal when m3
      mAChRs were activated by moderate doses (1-10 microM) of carbachol, but
      substantially reduced at higher agonist concentrations. Manipulation of the
      membrane potential revealed that the carbachol-induced Ca2+ influx phase was
      diminished at depolarized potentials. Importantly, carbachol doses above 10
      microM were found to couple m3 mAChRs to the activation of an inward, monovalent
      cation current resulting in depolarization of the cell membrane and a selective
      decrease in the influx, but not release, component of the Ca2+ response. These
      studies demonstrate, in one experimental system, a mechanism by which a single
      subtype of G-protein-coupled receptor can utilize the information encoded in the
      concentration of an agonist to generate distinct intracellular Ca2+ signals.

PMID- 9606187
TI  - Defective smooth muscle regulation in cGMP kinase I-deficient mice.
AB  - Regulation of smooth muscle contractility is essential for many important
      biological processes such as tissue perfusion, cardiovascular haemostasis and
      gastrointestinal motility. While an increase in calcium initiates smooth muscle
      contraction, relaxation can be induced by cGMP or cAMP. cGMP-dependent protein
      kinase I (cGKI) has been suggested as a major mediator of the relaxant effects of
      both nucleotides. To study the biological role of cGKI and its postulated cross
      activation by cAMP, we inactivated the gene coding for cGKI in mice. Loss of cGKI
      abolishes nitric oxide (NO)/cGMP-dependent relaxation of smooth muscle, resulting
      in severe vascular and intestinal dysfunctions. However, cGKI-deficient smooth
      muscle responded normally to cAMP, indicating that cAMP and cGMP signal via
      independent pathways, with cGKI being the specific mediator of the NO/cGMP
      effects in murine smooth muscle.

PMID- 9606188
TI  - A homologue of Drosophila aurora kinase is oncogenic and amplified in human
      colorectal cancers.
AB  - Genetic and biochemical studies in lower eukaryotes have identified several
      proteins that ensure accurate segregation of chromosomes. These include the
      Drosophila aurora and yeast Ipl1 kinases that are required for centrosome
      maturation and chromosome segregation. We have identified two human homologues of
      these genes, termed aurora1 and aurora2, that encode cell-cycle-regulated
      serine/threonine kinases. Here we demonstrate that the aurora2 gene maps to
      chromosome 20q13, a region amplified in a variety of human cancers, including a
      significant number of colorectal malignancies. We propose that aurora2 may be a
      target of this amplicon since its DNA is amplified and its RNA overexpressed, in
      more than 50% of primary colorectal cancers. Furthermore, overexpression of
      aurora2 transforms rodent fibroblasts. These observations implicate aurora2 as a
      potential oncogene in many colon, breast and other solid tumors, and identify
      centrosome-associated proteins as novel targets for cancer therapy.

PMID- 9606189
TI  - Nascent transcription from the nmt1 and nmt2 genes of Schizosaccharomyces pombe
      overlaps neighbouring genes.
AB  - We have determined the extent of the primary transcription unit for the two
      highly expressed genes nmt1 and nmt2 of Schizosaccharomyces pombe. Transcription
      run-on analysis in permeabilized yeast cells was employed to map polymerase
      density across the 3'-flanking region of these two genes. Surprisingly,
      polymerases were detected 4.3 kb beyond the nmt1 polyadenylation [poly(A)] site
      and 2.4 kb beyond the nmt2 poly(A) site, which in each case have transcribed
      through an entire convergent downstream transcription unit. However, the steady
      state levels of both downstream genes were unaffected by the high level of nmt1
      or nmt2 nascent transcription. Analysis of nmt1 and nmt2 RNA 3' end formation
      signals indicates that efficient termination of transcription requires not only a
      poly(A) signal but also additional pause elements. The absence of such pause
      elements close to the poly(A) sites of these genes may account for their extended
      nascent transcripts.

PMID- 9606191
TI  - Direct binding of Smad3 and Smad4 to critical TGF beta-inducible elements in the
      promoter of human plasminogen activator inhibitor-type 1 gene.
AB  - Smad proteins play a key role in the intracellular signalling of transforming
      growth factor beta (TGF beta), which elicits a large variety of cellular
      responses. Upon TGF beta receptor activation, Smad2 and Smad3 become
      phosphorylated and form heteromeric complexes with Smad4. These complexes
      translocate to the nucleus where they control expression of target genes.
      However, the mechanism by which Smads mediate transcriptional regulation is
      largely unknown. Human plasminogen activator inhibitor-1 (PAI-1) is a gene that
      is potently induced by TGF beta. Here we report the identification of Smad3/Smad4
      binding sequences, termed CAGA boxes, within the promoter of the human PAI-1
      gene. The CAGA boxes confer TGF beta and activin, but not bone morphogenetic
      protein (BMP) stimulation to a heterologous promoter reporter construct.
      Importantly, mutation of the three CAGA boxes present in the PAI-1 promoter was
      found to abolish TGF beta responsiveness. Thus, CAGA elements are essential and
      sufficient for the induction by TGF beta. In addition, TGFbeta induces the
      binding of a Smad3/Smad4-containing nuclear complex to CAGA boxes. Furthermore,
      bacterially expressed Smad3 and Smad4 proteins, but not Smad1 nor Smad2 protein,
      bind directly to this sequence in vitro. The presence of this box in TGF beta
      responsive regions of several other genes suggests that this may be a widely used
      motif in TGF beta-regulated transcription.

PMID- 9606190
TI  - Implication of a multisubunit Ets-related transcription factor in synaptic
      expression of the nicotinic acetylcholine receptor.
AB  - In adult muscle, transcription of the nicotinic acetylcholine receptor (AChR) is
      restricted to the nuclei located at the neuromuscular junction. The N-box, a new
      promoter element, was identified recently and shown to contribute to this
      compartmentalized synaptic expression of the AChR delta- and epsilon-subunits. We
      demonstrate that the N-box mediates transcriptional activation in cultured
      myotubes and identify the transcription factor that binds to the N-box as a
      heterooligomer in myotubes and adult muscle. The GABP (GA-binding protein) alpha
      subunit belongs to the Ets family of transcription factors, whereas the beta
      subunit shares homology with IkappaB and Drosophila Notch protein. GABP binding
      specificity to mutated N-box in vitro strictly parallels the sequence requirement
      for beta-galactosidase targeting to the endplate in vivo. In situ hybridization
      studies reveal that the mRNAs of both GABP subunits are abundant in mouse
      diaphragm, with preferential expression of the alpha-subunit at motor endplates.
      In addition, heregulin increases GABPalpha protein levels and regulates
      phosphorylation of both subunits in cultured chick myotubes. Finally, dominant
      negative mutants of either GABPalpha or GABPbeta block heregulin-elicited
      transcriptional activation of the AChR delta and epsilon genes. These findings
      establish the expected connection with a presynaptic trophic factor whose release
      contributes to the accumulation of AChR subunit mRNAs at the motor endplate.

PMID- 9606192
TI  - Calcineurin preferentially synergizes with PKC-theta to activate JNK and IL-2
      promoter in T lymphocytes.
AB  - Costimulation of the T cell receptor (TCR) and CD28 is required for optimal
      interleukin-2 (IL-2) induction. These signals, which can be replaced by the
      pharmacological agents phorbol ester (PMA) and Ca2+ ionophore, synergistically
      activate the mitogen-activated protein kinase (MAPK) JNK. Cyclosporin A, an
      inhibitor of the Ca2+-dependent phosphatase calcineurin which blocks IL-2
      induction, abrogates Ca2+-triggered synergistic JNK activation. As protein kinase
      C (PKC) downregulation inhibits PMA+ionophore-induced JNK activation, we examined
      whether a particular PKC isoform is preferentially involved in this response. We
      found that PKC-theta but neither PKC-alpha nor PKC-epsilon participates in JNK
      activation, whereas all three PKCs lead to ERK MAPK activation. PKC-theta
      specifically cooperates with calcineurin, and together their signals converge on
      (or upstream of) Rac leading to potent JNK activation. Similarly, calcineurin and
      PKC-theta specifically synergize to induce transcription of reporters driven by
      the c-jun and IL-2 promoters. PKC-theta and calcineurin are also partially
      responsible for the synergistic activation of JNK following TCR and CD28
      ligation. Preferential cooperation between PKC-theta and calcineurin is observed
      in Jurkat T cells but not in HeLa cells. These results indicate that PKC isozymes
      have distinct biological functions and suggest that synergistic JNK activation is
      an important function for PKC-theta in T-cell activation.

PMID- 9606193
TI  - p53 is a general repressor of RNA polymerase III transcription.
AB  - p53 is a major tumour suppressor that is inactivated in a large proportion of
      human cancers. We show that p53 serves as a general repressor of transcription by
      RNA polymerase (pol) III. It can inhibit the synthesis of a range of essential
      small cellular RNAs including tRNA, 5S rRNA and U6 snRNA, as well as viral
      products such as the adenovirus VAI RNA. Fibroblasts derived from p53 knock-out
      mice display a substantial increase in pol III transcriptional activity.
      Endogenous cellular p53 is shown to interact with the TATA-binding protein (TBP)
      containing general factor TFIIIB, thereby compromising its function severely.
      However, assembly of TFIIIB into a pre-initiation complex confers substantial
      protection against the inhibitory effects of p53. Since TFIIIB is an essential
      determinant of the biosynthetic capacity of cells, its release from repression by
      p53 may contribute to a loss of growth control during the development of many
      tumours.

PMID- 9606194
TI  - Modulation of cytokine-induced HIV gene expression by competitive binding of
      transcription factors to the coactivator p300.
AB  - The host response to viral infection involves the secretion of multiple cytokines
      which alter immune function and viral replication. These proteins activate
      several signal transduction pathways in infected cells which must be integrated
      to regulate cellular and viral gene expression. In this report, we demonstrate
      that specific transcription factors induced by distinct cytokines regulate HIV
      transcription by competitive binding to the p300 coactivator. Interferon-alpha
      (IFN-alpha) was found to inhibit NF-kappaB-dependent HIV gene expression
      stimulated by tumor necrosis factor-alpha (TNF-alpha). This inhibition was
      mediated by binding of the IFN-alpha signal transducer and activator of
      transcription 2, Stat2, to a specific domain of p300 which also binds to the RelA
      (p65) subunit of NF-kappaB. p300 was found to be limiting with respect to RelA
      (p65) and Stat2, and this effect was reversed by overexpression of p300.
      Inhibition by Stat2 was specific for NF-kappaB and was not mediated by Stat1,
      which is also induced by IFN-alpha. Gene activation induced by the Stat2
      transcription domain was also inhibited by expression of RelA. These results
      demonstrate that HIV transcription can be regulated in the nucleus by competitive
      binding of specific cytokine-induced transcription factors to a discrete domain
      of a transcriptional coactivator.

PMID- 9606195
TI  - TTF-I determines the chromatin architecture of the active rDNA promoter.
AB  - Transcription of ribosomal genes assembled into chromatin requires binding of the
      transcription termination factor TTF-I to the promoter-proximal terminator T0. To
      analyze the mechanism of TTF-I-mediated transcriptional activation, we have used
      mutant templates with altered sequence, polarity and distance of T0 with respect
      to the transcription start site. Transcription activation by TTF-I is chromatin
      specific and requires the precise positioning of the terminator relative to the
      promoter. Whereas termination by TTF-I depends on the correct orientation of a
      terminator, TTF-I-mediated transcriptional activation is orientation independent.
      TTF-I can bind to nucleosomal DNA in the absence of enzymatic activities that
      destabilize nucleosome structure. Chromatin-bound TTF-I synergizes with ATP
      dependent cofactors present in extracts of Drosophila embryos and mouse cells to
      position a nucleosome over the rDNA promoter and the transcription start site.
      Nucleosome positioning correlates tightly with the activation of rDNA
      transcription. We suggest that transcriptional activation by TTF-I is a stepwise
      process involving the creation of a defined promoter architecture and that the
      positioning of a nucleosome is compatible with, if not a prerequisite for,
      transcription initiation from rDNA chromatin.

PMID- 9606196
TI  - Transcriptional activation domains stimulate initiation and elongation at
      different times and via different residues.
AB  - Transcriptional activators can stimulate multiple steps in the transcription
      process. We have used GAL4 fusion proteins to characterize the ability of
      different transcriptional activation domains to stimulate transcriptional
      elongation on the hsp70 gene in vitro. Stimulation of elongation apparently
      occurs via a mechanistic pathway different from that of stimulation of
      initiation: the herpes simplex virus VP16, heat shock factor 1 (HSF1) and
      amphipathic helix (AH) activation domains all stimulate initiation, but only VP16
      and HSF1 stimulate elongation; and mutations in hydrophobic residues of the HSF1
      activation domains impair stimulation of elongation but not of initiation, while
      mutations in adjacent acidic residues impair stimulation of initiation more than
      of elongation. Experiments in which activators were exchanged between initiation
      and elongation demonstrate that the elongation function of HSF1 will stimulate
      RNA polymerase that has initiated and is transcriptionally engaged.
      Transcriptional activators thus appear to have at least two distinct functions
      that reside in the same domain, and that act at different times to stimulate
      initiation and elongation.

PMID- 9606197
TI  - Essential and redundant functions of histone acetylation revealed by mutation of
      target lysines and loss of the Gcn5p acetyltransferase.
AB  - The Gcn5p histone acetyltransferase exhibits a limited substrate specificity in
      vitro. However, neither the specificity of this enzyme in vivo nor the importance
      of particular acetylated residues to transcription or cell growth are well
      defined. To probe these questions, we mutated specific lysines in the N-termini
      of histones H3 and H4 and examined the effects of these mutations in yeast
      strains with and without functional GCN5. We found that in vivo, GCN5 is required
      either directly or indirectly for the acetylation of several sites in H3 and H4
      in addition to those recognized by the recombinant enzyme in vitro. Moreover, in
      the absence of GCN5, cells accumulate in G2/M indicating that Gcn5p functions are
      important for normal cell-cycle progression. Mutation of K14 in H3, which serves
      as the major target of recombinant Gcn5p acetylation in vitro, confers a strong,
      synthetic growth defect in gcn5 cells. Synergistic growth defects were also
      observed in gcn5 cells carrying mutations in lysine pairs (K8/K16 or K5/K12) in
      histone H4. Strikingly, simultaneous mutation of K14 in H3 and K8 and K16 in H4
      to arginine, or deletion of either the H3 or the H4 N-terminal tail, results in
      the death of gcn5 cells. Mutation of these same three sites to glutamine is not
      lethal. Indeed, this combination of mutations largely bypasses the need for GCN5
      for transcriptional activation by Gal4-VP16, supporting an important role for
      histone acetylation in Gcn5p-mediated regulation of transcription. Our data
      indicate that acetylation of particular lysines in histones H3 and H4 serves both
      unique and overlapping functions important for normal cell growth, and that a
      critical overall level of histone acetylation is essential for cell viability.

PMID- 9606198
TI  - Meiotic maturation in Xenopus requires polyadenylation of multiple mRNAs.
AB  - Cytoplasmic polyadenylation of specific mRNAs commonly is correlated with their
      translational activation during development. Here, we focus on links between
      cytoplasmic polyadenylation, translational activation and the control of meiotic
      maturation in Xenopus oocytes. We manipulate endogenous c-mos mRNA, which encodes
      a protein kinase that regulates meiotic maturation. We determined that
      translational activation of endogenous c-mos mRNA requires a long poly(A) tail
      per se, rather than the process of polyadenylation. For this, we injected
      'prosthetic' poly(A)_synthetic poly(A) tails designed to attach by base pairing
      to endogenous c-mos mRNA that has had its own polyadenylation signals removed.
      This prosthetic poly(A) tail activates c-mos translation and restores meiotic
      maturation in response to progesterone. Thus the role of polyadenylation in
      activating c-mos mRNA differs from its role in activating certain other mRNAs,
      for which the act of polyadenylation is required. In the absence of progesterone,
      prosthetic poly(A) does not stimulate c-mos expression, implying that
      progesterone acts at additional steps to elevate c-Mos protein. By using a
      general inhibitor of polyadenylation together with prosthetic poly(A), we
      demonstrate that these additional steps include polyadenylation of at least one
      other mRNA, in addition to that of c-mos mRNA. These other mRNAs, encoding
      regulators of meiotic maturation, act upstream of c-Mos in the meiotic maturation
      pathway.

PMID- 9606199
TI  - Conserved boxes C and D are essential nucleolar localization elements of U14 and
      U8 snoRNAs.
AB  - Sequences necessary for nucleolar targeting were identified in Box C/D small
      nucleolar RNAs (snoRNAs) by fluorescence microscopy. Nucleolar preparations were
      examined after injecting fluorescein-labelled wild-type and mutated U14 or U8
      snoRNA into Xenopus oocyte nuclei. Regions in U14 snoRNA that are complementary
      to 18S rRNA and necessary for rRNA processing and methylation are not required
      for nucleolar localization. Truncated U14 molecules containing Boxes C and D with
      or without the terminal stem localized efficiently. Nucleolar localization was
      abolished upon mutating just one or two nucleotides within Boxes C and D.
      Moreover, the spatial position of Boxes C or D in the molecule is essential.
      Mutations in Box C/D of U8 snoRNA also impaired nucleolar localization,
      suggesting the general importance of Boxes C and D as nucleolar localization
      sequences for Box C/D snoRNAs. U14 snoRNA is shown to be required for 18S rRNA
      production in vertebrates.

PMID- 9606200
TI  - Presence and location of modified nucleotides in Escherichia coli tmRNA:
      structural mimicry with tRNA acceptor branches.
AB  - Escherichia coli tmRNA functions uniquely as both tRNA and mRNA and possesses
      structural elements similar to canonical tRNAs. To test whether this mimicry
      extends to post-transcriptional modification, the technique of combined liquid
      chromatography/ electrospray ionization mass spectrometry (LC/ESIMS) and sequence
      data were used to determine the molecular masses of all oligonucleotides produced
      by RNase T1 hydrolysis with a mean error of 0.1 Da. Thus, this allowed for the
      detection, chemical characterization and sequence placement of modified
      nucleotides which produced a change in mass. Also, chemical modifications were
      used to locate mass-silent modifications. The native E.coli tmRNA contains two
      modified nucleosides, 5-methyluridine and pseudouridine. Both modifications are
      located within the proposed tRNA-like domain, in a seven-nucleotide loop
      mimicking the conserved sequence of T loops in canonical tRNAs. Although tmRNA
      acceptor branches (acceptor stem and T stem-loop) utilize different architectural
      rules than those of canonical tRNAs, their conformations in solution may be very
      similar. A comparative structural and functional analysis of unmodified tmRNA
      made by in vitro transcription and native E.coli tmRNA suggests that one or both
      of these post-transcriptional modifications may be required for optimal stability
      of the acceptor branch which is needed for efficient aminoacylation.

PMID- 9606201
TI  - CCA addition by tRNA nucleotidyltransferase: polymerization without
      translocation?
AB  - The CCA-adding enzyme repairs the 3'-terminal CCA sequence of all tRNAs. To
      determine how the enzyme recognizes tRNA, we probed critical contacts between
      tRNA substrates and the archaeal Sulfolobus shibatae class I and the eubacterial
      Escherichia coli class II CCA-adding enzymes. Both CTP addition to tRNA-C and ATP
      addition to tRNA-CC were dramatically inhibited by alkylation of the same tRNA
      phosphates in the acceptor stem and TPsiC stem-loop. Both enzymes also protected
      the same tRNA phosphates in tRNA-C and tRNA-CC. Thus the tRNA substrate must
      remain fixed on the enzyme surface during CA addition. Indeed, tRNA-C cross
      linked to the S. shibatae enzyme remains fully active for addition of CTP and
      ATP. We propose that the growing 3'-terminus of the tRNA progressively refolds to
      allow the solitary active site to reuse a single CTP binding site. The ATP
      binding site would then be created collaboratively by the refolded CC terminus
      and the enzyme, and nucleotide addition would cease when the nucleotide binding
      pocket is full. The template for CCA addition would be a dynamic
      ribonucleoprotein structure.

PMID- 9606202
TI  - Inhibition of Escherichia coli RecA coprotease activities by DinI.
AB  - In Escherichia coli, the SOS response is induced upon DNA damage and results in
      the enhanced expression of a set of genes involved in DNA repair and other
      functions. The initial step, self-cleavage of the LexA repressor, is promoted by
      the RecA protein which is activated upon binding to single-stranded DNA. In this
      work, induction of the SOS response by the addition of mitomycin C was found to
      be prevented by overexpression of the dinI gene. dinI is an SOS gene which maps
      at 24.6 min of the E.coli chromosome and encodes a small protein of 81 amino
      acids. Immunoblotting analysis with anti-LexA antibodies revealed that LexA did
      not undergo cleavage in dinI-overexpressed cells after UV irradiation. In
      addition, the RecA-dependent conversion of UmuD to UmuD' (the active form for
      mutagenesis) was also inhibited in dinI-overexpressed cells. Conversely, a dinI
      deficient mutant showed a slightly faster and more extensive processing of UmuD
      and hence higher mutability than the wild-type. Finally, we demonstrated, by
      using an in vitro reaction with purified proteins, that DinI directly inhibits
      the ability of RecA to mediate self-cleavage of UmuD.

PMID- 9606203
TI  - The influence of huntingtin protein size on nuclear localization and cellular
      toxicity.
AB  - Huntington disease is an autosomal dominant neurodegenerative disorder caused by
      the pathological expansion of a polyglutamine tract. In this study we directly
      assess the influence of protein size on the formation and subcellular
      localization of huntingtin aggregates. We have created numerous deletion
      constructs expressing successively smaller fragments of huntingtin and show that
      these smaller proteins containing 128 glutamines form both intranuclear and
      perinuclear aggregates. In contrast, larger NH2-terminal fragments of huntingtin
      proteins with 128 glutamines form exclusively perinuclear aggregates. These
      aggregates can form in the absence of endogenous huntingtin. Furthermore,
      expression of mutant huntingtin results in increased susceptibility to apoptotic
      stress that is greater with decreasing protein length and increasing
      polyglutamine size. As both intranuclear and perinuclear aggregates are clearly
      associated with increased cellular toxicity, this supports an important role for
      toxic polyglutamine-containing fragments forming aggregates and playing a key
      role in the pathogenesis of Huntington disease.

PMID- 9606204
TI  - Sec35p, a novel peripheral membrane protein, is required for ER to Golgi vesicle
      docking.
AB  - SEC35 was identified in a novel screen for temperature-sensitive mutants in the
      secretory pathway of the yeast Saccharomyces cerevisiae (. Genetics. 142:393
      406). At the restrictive temperature, the sec35-1 strain exhibits a transport
      block between the ER and the Golgi apparatus and accumulates numerous vesicles.
      SEC35 encodes a novel cytosolic protein of 32 kD, peripherally associated with
      membranes. The temperature-sensitive phenotype of sec35-1 is efficiently
      suppressed by YPT1, which encodes the rab-like GTPase required early in the
      secretory pathway, or by SLY1-20, which encodes a dominant form of the ER to
      Golgi target -SNARE-associated protein Sly1p. Weaker suppression is evident upon
      overexpression of genes encoding the vesicle-SNAREs SEC22, BET1, or YKT6. The
      cold-sensitive lethality that results from deleting SEC35 is suppressed by YPT1
      or SLY1-20. These genetic relationships suggest that Sec35p acts upstream of, or
      in conjunction with, Ypt1p and Sly1p as was previously found for Uso1p. Using a
      cell-free assay that measures distinct steps in vesicle transport from the ER to
      the Golgi, we find Sec35p is required for a vesicle docking stage catalyzed by
      Uso1p. These genetic and biochemical results suggest Sec35p acts with Uso1p to
      dock ER-derived vesicles to the Golgi complex.

PMID- 9606205
TI  - Deficient peptide loading and MHC class II endosomal sorting in a human genetic
      immunodeficiency disease: the Chediak-Higashi syndrome.
AB  - The Chediak-Higashi syndrome (CHS) is a human recessive autosomal disease caused
      by mutations in a single gene encoding a protein of unknown function, called
      lysosomal-trafficking regulator. All cells in CHS patients bear enlarged
      lysosomes. In addition, T- and natural killer cell cytotoxicity is defective in
      these patients, causing severe immunodeficiencies. We have analyzed major
      histocompatibility complex class II functions and intracellular transport in
      Epstein Barr Virus-transformed B cells from CHS patients. Peptide loading onto
      major histocompatibility complex class II molecules and antigen presentation are
      strongly delayed these cells. A detailed electron microscopy analysis of
      endocytic compartments revealed that only lysosomal multilaminar compartments are
      enlarged (reaching 1-2 micron), whereas late multivesicular endosomes have normal
      size and morphology. In contrast to giant multilaminar compartments that bear
      most of the usual lysosomal markers in these cells (HLA-DR, HLA-DM, Lamp-1, CD63,
      etc.), multivesicular late endosomes displayed reduced levels of all these
      molecules, suggesting a defect in transport from the trans-Golgi network and/or
      early endosomes into late multivesicular endosomes. Further insight into a
      possible mechanism of this transport defect came from immunolocalizing the
      lysosomal trafficking regulator protein, as antibodies directed to a peptide from
      its COOH terminal domain decorated punctated structures partially aligned along
      microtubules. These results suggest that the product of the Lyst gene is required
      for sorting endosomal resident proteins into late multivesicular endosomes by a
      mechanism involving microtubules.

PMID- 9606206
TI  - Patterning muscles using organizers: larval muscle templates and adult myoblasts
      actively interact to pattern the dorsal longitudinal flight muscles of
      Drosophila.
AB  - Pattern formation in muscle development is often mediated by special cells called
      muscle organizers. During metamorphosis in Drosophila, a set of larval muscles
      function as organizers and provide scaffolding for the development of the dorsal
      longitudinal flight muscles. These organizers undergo defined morphological
      changes and dramatically split into templates as adult fibers differentiate
      during pupation. We have investigated the cellular mechanisms involved in the use
      of larval fibers as templates. Using molecular markers that label myoblasts and
      the larval muscles themselves, we show that splitting of the larval muscles is
      concomitant with invasion by imaginal myoblasts and the onset of differentiation.
      We show that the Erect wing protein, an early marker of muscle differentiation,
      is not only expressed in myoblasts just before and after fusion, but also in
      remnant larval nuclei during muscle differentiation. We also show that
      interaction between imaginal myoblasts and larval muscles is necessary for
      transformation of the larval fibers. In the absence of imaginal myoblasts, the
      earliest steps in metamorphosis, such as the escape of larval muscles from
      histolysis and changes in their innervation, are normal. However, subsequent
      events, such as the splitting of these muscles, fail to progress. Finally, we
      show that in a mutant combination, null for Erect wing function in the mesoderm,
      the splitting of the larval muscles is aborted. These studies provide a genetic
      and molecular handle for the understanding of mechanisms underlying the use of
      muscle organizers in muscle patterning. Since the use of such organizers is a
      common theme in myogenesis in several organisms, it is likely that many of the
      processes that we describe are conserved.

PMID- 9606207
TI  - A role for Cdc42 in macrophage chemotaxis.
AB  - Three members of the Rho family, Cdc42, Rac, and Rho are known to regulate the
      organization of actin-based cytoskeletal structures. In Bac1.2F5 macrophages, we
      have shown that Rho regulates cell contraction, whereas Rac and Cdc42 regulate
      the formation of lamellipodia and filopodia, respectively. We have now tested the
      roles of Cdc42, Rac, and Rho in colony stimulating factor-1 (CSF-1)-induced
      macrophage migration and chemotaxis using the Dunn chemotaxis chamber.
      Microinjection of constitutively activated RhoA, Rac1, or Cdc42 inhibited cell
      migration, presumably because the cells were unable to polarize significantly in
      response to CSF-1. Both Rho and Rac were required for CSF-1-induced migration,
      since migration speed was reduced to background levels in cells injected with C3
      transferase, an inhibitor of Rho, or with the dominant-negative Rac mutant,
      N17Rac1. In contrast, cells injected with the dominant-negative Cdc42 mutant,
      N17Cdc42, were able to migrate but did not polarize in the direction of the
      gradient, and chemotaxis towards CSF-1 was abolished. We conclude that Rho and
      Rac are required for the process of cell migration, whereas Cdc42 is required for
      cells to respond to a gradient of CSF-1 but is not essential for cell locomotion.

PMID- 9606208
TI  - ZYG-9, a Caenorhabditis elegans protein required for microtubule organization and
      function, is a component of meiotic and mitotic spindle poles.
AB  - We describe the molecular characterization of zyg-9, a maternally acting gene
      essential for microtubule organization and function in early Caenorhabditis
      elegans embryos. Defects in zyg-9 mutants suggest that the zyg-9 product
      functions in the organization of the meiotic spindle and the formation of long
      microtubules. One-cell zyg-9 embryos exhibit both meiotic and mitotic spindle
      defects. Meiotic spindles are disorganized, pronuclear migration fails, and the
      mitotic apparatus forms at the posterior, orients incorrectly, and contains
      unusually short microtubules. We find that zyg-9 encodes a component of the
      meiotic and mitotic spindle poles. In addition to the strong staining of spindle
      poles, we consistently detect staining in the region of the kinetochore
      microtubules at metaphase and early anaphase in mitotic spindles. The ZYG-9
      signal at the mitotic centrosomes is not reduced by nocodazole treatment,
      indicating that ZYG-9 localization to the mitotic centrosomes is not dependent
      upon long astral microtubules. Interestingly, in embryos lacking an organized
      meiotic spindle, produced either by nocodazole treatment or mutations in the mei
      1 gene, ZYG-9 forms a halo around the meiotic chromosomes. The protein sequence
      shows partial similarity to a small set of proteins that also localize to spindle
      poles, suggesting a common activity of the proteins.

PMID- 9606209
TI  - The yeast spindle pole body component Spc72p interacts with Stu2p and is required
      for proper microtubule assembly.
AB  - We have previously shown that Stu2p is a microtubule-binding protein and a
      component of the Saccharomyces cerevisiae spindle pole body (SPB). Here we report
      the identification of Spc72p, a protein that interacts with Stu2p. Stu2p and
      Spc72p associate in the two-hybrid system and can be coimmunoprecipitated from
      yeast extracts. Stu2p and Spc72p also interact with themselves, suggesting the
      possibility of a multimeric Stu2p-Spc72p complex. Spc72p is an essential
      component of the SPB and is able to associate with a preexisting SPB, indicating
      that there is a dynamic exchange between soluble and SPB forms of Spc72p. Unlike
      Stu2p, Spc72p does not bind microtubules in vitro, and was not observed to
      localize along microtubules in vivo. A temperature-sensitive spc72 mutation
      causes defects in SPB morphology. In addition, most spc72 mutant cells lack
      cytoplasmic microtubules; the few cytoplasmic microtubules that are observed are
      excessively long, and some of these are unattached to the SPB. spc72 cells are
      able to duplicate and separate their SPBs to form a bipolar spindle, but spindle
      elongation and chromosome segregation rarely occur. The chromosome segregation
      block does not arrest the cell cycle; instead, spc72 cells undergo cytokinesis,
      producing aploid cells and polyploid cells that contain multiple SPBs.

PMID- 9606210
TI  - Localization of Mad2 to kinetochores depends on microtubule attachment, not
      tension.
AB  - A single unattached kinetochore can delay anaphase onset in mitotic tissue
      culture cells (Rieder, C.L., A. Schultz, R. Cole, G. Sluder. 1994. J. Cell Biol.
      127:1301-1310). Kinetochores in vertebrate cells contain multiple binding sites,
      and tension is generated at kinetochores after attachment to the plus ends of
      spindle microtubules. Checkpoint component Mad2 localizes selectively to
      unattached kinetochores (Chen, R.-H., J.C. Waters, E.D. Salmon, and A.W. Murray.
      1996. Science. 274:242-246; Li, Y., and R. Benezra. Science. 274: 246-248) and
      disappears from kinetochores by late metaphase, when chromosomes are properly
      attached to the spindle. Here we show that Mad2 is lost from PtK1 cell
      kinetochores as they accumulate microtubules and re-binds previously attached
      kinetochores after microtubules are depolymerized with nocodazole. We also show
      that when kinetochore microtubules in metaphase cells are stabilized with taxol,
      tension at kinetochores is lost. The phosphoepitope 3f3/2, which has been shown
      to become dephosphorylated in response to tension at the kinetochore (Nicklas,
      R.B., S.C. Ward, and G.J. Gorbsky. 1995. J. Cell Biol. 130:929-939), is
      phosphorylated on all 22 kinetochores after tension is reduced with taxol. In
      contrast, Mad2 only localized to an average of 2.6 out of the 22 kinetochores in
      taxol-treated PtK1 cells. Therefore, loss of tension at kinetochores occupied by
      microtubules is insufficient to induce Mad2 to accumulate on kinetochores,
      whereas unattached kinetochores consistently bind Mad2. We also found that
      microinjecting antibodies against Mad2 caused cells arrested with taxol to exit
      mitosis after approximately 12 min, while uninjected cells remained in mitosis
      for at least 6 h, demonstrating that Mad2 is necessary for maintenance of the
      taxol-induced mitotic arrest. We conclude that kinetochore microtubule attachment
      stops the Mad2 interactions at kinetochores which are important for inhibiting
      anaphase onset.

PMID- 9606211
TI  - Microinjection of antibody to Mad2 protein into mammalian cells in mitosis
      induces premature anaphase.
AB  - In yeast, the Mad2 protein is required for the M phase arrest induced by
      microtubule inhibitors, but the protein is not essential under normal culture
      conditions. We tested whether the Mad2 protein participates in regulating the
      timing of anaphase onset in mammalian cells in the absence of microtubule drugs.
      When microinjected into living prophase or prometaphase PtK1 cells, anti-Mad2
      antibody induced the onset of anaphase prematurely during prometaphase, before
      the chromosomes had assembled at the metaphase plate. Anti-Mad2 antibody-injected
      cells completed all aspects of anaphase including chromatid movement to the
      spindle poles and pole-pole separation. Identical results were obtained when
      primary human keratinocytes were injected with anti-Mad2 antibody. These studies
      suggest that Mad2 protein function is essential for the timing of anaphase onset
      in somatic cells at each mitosis. Thus, in mammalian somatic cells, the spindle
      checkpoint appears to be a component of the timing mechanism for normal mitosis,
      blocking anaphase onset until all chromosomes are aligned at the metaphase plate.

PMID- 9606212
TI  - Differential subcellular localization of protein phosphatase-1 alpha, gamma1, and
      delta isoforms during both interphase and mitosis in mammalian cells.
AB  - Protein phosphatase-1 (PP-1) is involved in the regulation of numerous metabolic
      processes in mammalian cells. The major isoforms of PP-1, alpha, gamma1, and
      delta, have nearly identical catalytic domains, but they vary in sequence at
      their extreme NH2 and COOH termini. With specific antibodies raised against the
      unique COOH-terminal sequence of each isoform, we find that the three PP-1
      isoforms are each expressed in all mammalian cells tested, but that they localize
      within these cells in a strikingly distinct and characteristic manner. Each
      isoform is present both within the cytoplasm and in the nucleus during
      interphase. Within the nucleus, PP-1 alpha associates with the nuclear matrix, PP
      1 gamma1 concentrates in nucleoli in association with RNA, and PP-1 delta
      localizes to nonnucleolar whole chromatin. During mitosis, PP-1 alpha is
      localized to the centrosome, PP-1 gamma1 is associated with microtubules of the
      mitotic spindle, and PP-1 delta strongly associates with chromosomes. We conclude
      that PP-1 isoforms are targeted to strikingly distinct and independent sites in
      the cell, permitting unique and independent roles for each of the isoforms in
      regulating discrete cellular processes.

PMID- 9606213
TI  - FH3, a domain found in formins, targets the fission yeast formin Fus1 to the
      projection tip during conjugation.
AB  - Formins are involved in diverse aspects of morphogenesis, and share two regions
      of homology: FH1 and FH2. We describe a new formin homology region, FH3. FH3 is
      an amino-terminal domain that differs from the Rho binding site identified in
      Bni1p and p140mDia. The Schizosaccharomyces pombe formin Fus1 is required for
      conjugation, and is localized to the projection tip in cells of mating pairs. We
      replaced genomic fus1+ with green fluorescent protein (GFP)- tagged versions that
      lacked either the FH1, FH2, or FH3 domain. Deletion of any FH domain essentially
      abolished mating. FH3, but neither FH1 nor FH2, was required for Fus1
      localization. An FH3 domain-GFP fusion protein localized to the projection tips
      of mating pairs. Thus, the FH3 domain alone can direct protein localization. The
      FH3 domains of both Fus1 and the S. pombe cytokinesis formin Cdc12 were able to
      localize GFP to the spindle pole body in half of the late G2 cells in a
      vegetatively growing population. Expression of both FH3-GFP fusions also affected
      cytokinesis. Overexpression of the spindle pole body component Sad1 altered the
      distribution of both Sad1 and the FH3-GFP domain. Together these data suggest
      that proteins at multiple sites can interact with FH3 domains.

PMID- 9606215
TI  - Death-effector filaments: novel cytoplasmic structures that recruit caspases and
      trigger apoptosis.
AB  - The death-effector domain (DED) is a critical protein interaction domain that
      recruits caspases into complexes with members of the TNF-receptor superfamily.
      Apoptosis can also be induced by expressing certain DED-containing proteins
      without surface receptor cross-linking. Using Green Fluorescent Protein to
      examine DED-containing proteins in living cells, we show that these proteins
      cause apoptosis by forming novel cytoplasmic filaments that recruit and activate
      pro-caspase zymogens. Formation of these filaments, which we term death-effector
      filaments, was blocked by coexpression of viral antiapoptotic DED-containing
      proteins, but not by bcl-2 family proteins. Thus, formation of death-effector
      filaments allows a regulated intracellular assembly of apoptosis-signaling
      complexes that can initiate or amplify apoptotic stimuli independently of
      receptors at the plasma membrane.

PMID- 9606214
TI  - Defining the interactions between intermediate filaments and desmosomes.
AB  - Desmoplakin (DP), plakoglobin (PG), and plakophilin 1 (PP1) are desmosomal
      components lacking a transmembrane domain, thus making them candidate linker
      proteins for connecting intermediate filaments and desmosomes. Using deletion and
      site-directed mutagenesis, we show that remarkably, removal of approximately 1%
      of DP's sequence obliterates its ability to associate with desmosomes.
      Conversely, when linked to a foreign protein, as few as 86 NH2-terminal DP
      residues are sufficient to target to desmosomes efficiently. In in vitro overlay
      assays, the DP head specifically associates with itself and with desmocollin 1a
      (Dsc1a). In similar overlay assays, PP1 binds to DP and Dsc1a, and to a lesser
      extent, desmoglein 1 (Dsg1), while PG binds to Dsg1 and more weakly to Dsc1a and
      DP. Interestingly, like DP, PG and PP1 associate with epidermal keratins,
      although PG is considerably weaker in its ability to do so. As judged by overlay
      assays, the amino terminal head domain of type II keratins appears to have a
      special importance in establishing these connections. Taken together, our
      findings provide new insights into the complexities of the links between
      desmosomes and intermediate filaments (IFs). Our results suggest a model whereby
      at desmosome sites within dividing epidermal cells, DP and PG anchor to
      desmosomal cadherins and to each other, forming an ordered array of
      nontransmembrane proteins that then bind to keratin IFs. As epidermal cells
      differentiate, PP1 is added as a molecular reinforcement to the plaque, enhancing
      anchorage to IFs and accounting at least partially for the increase in numbers
      and stability of desmosomes in suprabasal cells.

PMID- 9606216
TI  - E1B 19K inhibits Fas-mediated apoptosis through FADD-dependent sequestration of
      FLICE.
AB  - E1B 19K, the adenovirus Bcl-2 homologue, is a potent inhibitor of apoptosis
      induced by various stimuli including Fas and tumor necrosis factor-alpha. Fas and
      TNFR-1 belong to a family of cytokine-activated receptors that share key
      components in their signaling pathways, Fas-associating protein with death domain
      (FADD) and FADD-like interleukin-1beta-converting enzyme (FLICE), to induce an
      apoptotic response. We demonstrate here that E1B 19K and Bcl-xL are able to
      inhibit apoptosis induced by FADD, but not FLICE. Surprisingly, apoptosis was
      abrogated by E1B 19K and Bcl-xL when FADD and FLICE were coexpressed.
      Immunofluorescence studies demonstrated that FADD expression produced large
      insoluble death effector filaments that may represent oligomerized FADD. E1B 19K
      expression disrupted FADD filament formation causing FADD and FLICE to relocalize
      to membrane and cytoskeletal structures where E1B 19K is normally localized. E1B
      19K, however, does not detectably bind to FADD, nor does it inhibit FADD and
      FLICE from being recruited to the death-inducing signaling complex (DISC) when
      Fas is stimulated. Thus, E1B 19K may inhibit Fas-mediated cell death downstream
      of FADD recruitment of FLICE but upstream of FLICE activation by disrupting FADD
      oligomerization and sequestering an essential component of the DISC.

PMID- 9606217
TI  - Enhanced secretion of amylase from exocrine pancreas of connexin32-deficient
      mice.
AB  - To determine whether junctional communication between pancreatic acinar cells
      contributes to their secretory function in vivo, we have compared wild-type mice,
      which express the gap junctional proteins connexin32 (Cx32) and connexin26, to
      mice deficient for the Cx32 gene. Pancreatic acinar cells from Cx32 (-/-) mice
      failed to express Cx32 as evidenced by reverse transcription-PCR and
      immunolabeling and showed a marked reduction (4.8- and 25-fold, respectively) in
      the number and size of gap junctions. Dye transfer studies showed that the extent
      of intercellular communication was inhibited in Cx32 (-/-) acini. However,
      electrical coupling was detected by dual patch clamp recording in Cx32 (-/-)
      acinar cell pairs. Although wild-type and Cx32 (-/-) acini were similarly
      stimulated to release amylase by carbamylcholine, Cx32 (-/-) acini showed a
      twofold increase of their basal secretion. This effect was caused by an increase
      in the proportion of secreting acini, as detected with a reverse hemolytic plaque
      assay. Blood measurements further revealed that Cx32 (-/-) mice had elevated
      basal levels of circulating amylase. The results, which demonstrate an inverse
      relationship between the extent of acinar cell coupling and basal amylase
      secretion in vivo, support the view that the physiological recruitment of
      secretory acinar cells is regulated by gap junction mediated intercellular
      communication.

PMID- 9606218
TI  - Lumican regulates collagen fibril assembly: skin fragility and corneal opacity in
      the absence of lumican.
AB  - Lumican, a prototypic leucine-rich proteoglycan with keratan sulfate side chains,
      is a major component of the cornea, dermal, and muscle connective tissues. Mice
      homozygous for a null mutation in lumican display skin laxity and fragility
      resembling certain types of Ehlers-Danlos syndrome. In addition, the mutant mice
      develop bilateral corneal opacification. The underlying connective tissue defect
      in the homozygous mutants is deregulated growth of collagen fibrils with a
      significant proportion of abnormally thick collagen fibrils in the skin and
      cornea as indicated by transmission electron microscopy. A highly organized and
      regularly spaced collagen fibril matrix typical of the normal cornea is also
      missing in these mutant mice. This study establishes a crucial role for lumican
      in the regulation of collagen assembly into fibrils in various connective
      tissues. Most importantly, these results provide a definitive link between a
      necessity for lumican in the development of a highly organized collagenous matrix
      and corneal transparency.

PMID- 9606219
TI  - Magnetic resonance imaging of the brain in very preterm infants: visualization of
      the germinal matrix, early myelination, and cortical folding.
AB  - OBJECTIVE: To investigate preterm infants, we have installed in our neonatal
      intensive care unit a dedicated magnetic resonance (MR) imaging system which was
      specifically designed for neonatal use. The aim of this study was to describe the
      MR appearances of the brain in preterm infants who were first scanned between 25
      and 32 weeks gestational age (GA) and to outline changes to the brains of these
      infants between their first scan and term. METHODS: Preterm infants of 25 to 32
      weeks GA were imaged using the 1T neonatal MR system (Oxford Magnet Technology,
      Eyensham, Oxfordshire, England/Picker International, Cleveland, OH). The scanning
      protocol included T1-weighted conventional spin echo (repetition time [TR], 600;
      echo time, 20 ms), inversion recovery fast spin echo (TR, 3530; effective echo
      time, 30; inversion time, 950 ms), and T2-weighted fast spin echo (TR, 3500;
      effective echo time, 208 ms) sequences. RESULTS: Seventeen infants of median 28
      weeks GA (range, 24 to 31 weeks) at birth were imaged a total of 53 times between
      birth and term. The median number of images per infant was two (range, 1 to 9).
      In infants of < 30 weeks GA, the germinal matrix was visualized at the margins of
      the lateral ventricles. It had a short T1 and short T2 and the bulk of it
      involuted at between 30 and 32 weeks GA. The white matter had a relatively
      homogeneous low signal except for bands of altered signal (probably originating
      from regions containing radial glia and migrating cells) which were most apparent
      anterolateral and posterolateral to the lateral ventricles. Myelination was seen
      in the posterior brainstem, cerebellum, and region of the ventrolateral nuclei of
      the thalamus. Infants had very little cortical folding at 25 weeks GA but this
      developed later in an orderly fashion. CONCLUSION: The neonatal MR system allowed
      extremely preterm infants to be studied safely with MR imaging. The images
      acquired demonstrated the germinal matrix, early myelination, and early cortical
      folding. Evolution of these features was demonstrated with serial studies.

PMID- 9606220
TI  - Pediatric cardiac surgery: the effect of hospital and surgeon volume on in
      hospital mortality.
AB  - OBJECTIVE: To examine the relationship between annual provider (hospital and
      surgeon) volume of pediatric cardiac surgery and in-hospital mortality. DESIGN:
      Population-based retrospective cohort study using a clinical database. SETTING:
      The 16 acute care hospitals in New York with certificate of need approval to
      perform pediatric cardiac surgery. PATIENTS: All children undergoing congenital
      heart surgery in New York from 1992 to 1995. MAIN OUTCOME MEASURES: Risk-adjusted
      mortality rates for various hospital and surgeon volume ranges. Adjustments were
      made for severity of illness using logistic regression. RESULTS: A total of 7169
      cases were analyzed. After controlling for severity of preprocedural illness
      using clinical risk factors, hospitals with annual pediatric cardiac surgery
      volumes of fewer than 100 had significantly higher mortality rates (8.26%) than
      hospitals with volumes of 100 or more (5.95%), and surgeons with annual volumes
      of fewer than 75 had significantly higher mortality rates (8.77%) than surgeons
      with annual volumes of 75 or more (5.90%). CONCLUSIONS: Both hospital volume and
      surgeon volume are significantly associated with in-hospital mortality, and these
      differences persist for both high-complexity and low-complexity pediatric cardiac
      procedures.

PMID- 9606221
TI  - Initiating the first DTP vaccination age-appropriately: a model for understanding
      vaccination coverage.
AB  - OBJECTIVE: Our earlier research found that the strongest predictor of not being
      up to date on the full series of immunizations by 24 months is failure to receive
      the first diphtheria vaccine and tetanus toxoid and pertussis vaccine (DTP1) on
      time. To learn more about the relationship between successful vaccination during
      the DTP1 age-appropriate (DTP1-AA) period (between 42 and 92 days of life,
      inclusive) and an infant's early visit to the physician (before 42 days of life),
      we quantified children's progression through a sequence of provider visits and
      outcomes. DESIGN: This study analyzed data from 426 children living in the 57
      poorest census tracts in Baltimore. For each DTP1-AA visit, we calculated the
      percentage of times a DTP1-AA vaccination, provider missed opportunity, or
      deferral for a valid contraindication occurred. Relative and attributable risks
      were computed to assess associations between DTP1-AA vaccination and early visits
      and missed opportunities. RESULTS: We found the following: 1) Children who made a
      visit before 42 days of life were more than twice as likely to receive a DTP1-AA
      vaccination; 2) the missed opportunity rate for children who did not make an
      early visit was approximately twice that of the early-visit group; and 3) well
      visits were more likely to result in DTP1-AA immunization than sick visits.
      Attributable risk calculations show that DTP1-AA vaccination rates could be
      increased in this population by one third if all infants had an early visit.
      CONCLUSIONS: Early in-office visits seem to make DTP1-AA vaccination more likely.
      These rates may be amenable to intervention by increasing early visits and
      reducing DTP1-AA missed opportunities. Introduction of the hepatitis B vaccine to
      the recommended series may place more emphasis on early visits and result in
      increased DTP1-AA rates and, ultimately, higher vaccination coverage rates.

PMID- 9606222
TI  - Actuarial survival in the premature infant less than 30 weeks' gestation.
AB  - OBJECTIVE: Because survival from admission to discharge does not provide parents
      and physicians information about future life expectancy in the premature neonate,
      we characterized the actuarial survival, defined as the future life expectancy
      from a given postnatal age, in a large inborn population of premature infants <
      30 weeks' gestation. STUDY DESIGN: We determined daily actuarial survival of 1925
      inborn infants (23 to 29 weeks' gestation) admitted to the Baylor Affiliated
      Nurseries from July 1986 through December 1994, stratified by 100-g birth weight
      and by 1-week gestational-age intervals. RESULTS: In the 501- to 600-g birth
      weight stratum, actuarial survival improved from 31% at birth, to 61% on day of
      life 7, and then to 75% on day of life 28; in the 901- to 1000-g birth weight
      stratum, actuarial survival improved from 88%, to 94%, and then to 98% throughout
      the same times, respectively. Similar trends were obtained when data were
      stratified by gestational age. CONCLUSIONS: Survival in the smallest infants
      improves dramatically during the first few days of life, but there is a
      significant risk for late death in the smallest of these infants.

PMID- 9606223
TI  - Assessment of adenoidal obstruction in children: clinical signs versus
      roentgenographic findings.
AB  - OBJECTIVE: As part of a comprehensive study of indications for tonsillectomy and
      adenoidectomy, we investigated the reliability of standardized clinical
      assessments and standardized roentgenographic assessments of adenoidal
      obstruction of the nasopharynx, and the degree of correlation between clinical
      assessments and roentgenographic assessments. METHODS: We rated the degree of
      patients' mouth breathing and patients' speech hyponasality on a 4-point scale
      (none = 1; mild = 2; moderate = 3; marked = 4), we averaged the ratings for each
      child to obtain a Nasal Obstruction Index, and we determined levels of
      interobserver agreement concerning the ratings. We classified lateral soft-tissue
      roentgenograms of the nasopharynx, based on assessments of adenoid size and of
      nasopharyngeal airway patency, as showing either no obstruction, borderline
      obstruction, or obstruction, and we determined levels of inter- and intraobserver
      agreement concerning the classifications. Finally, we determined correlations in
      individual patients between clinical ratings and roentgenographic ratings of
      nasal/nasopharyngeal obstruction, and calculated the predictive values of
      clinical ratings based on roentgenographic ratings as the gold standard. RESULTS:
      In sets of paired examinations, weighted kappa values for interobserver agreement
      concerning mouth breathing (total, 235 children) and speech hyponasality (total,
      648 children) ranged from 0.84 to 0.91. The value for interobserver agreement
      concerning roentgenographic assessment of nasopharyngeal airway status (207
      children) was 0.92, and for intraobserver agreement (191 children) 0.88. The
      Kendall's tau b value for concordance between Nasal Obstruction Index values and
      roentgenographic ratings (1033 children) was 0.51. Nasal Obstruction Index values
      at the lower and upper extremes--i.e., 1.0 and > or = 3.5, respectively--were
      highly predictive of concordant roentgenographic ratings. CONCLUSIONS: We
      conclude that standardized clinical ratings of the degree of children's mouth
      breathing and speech hyponasality provide reliable and reasonably valid
      assessments of the presence and degree of adenoidal obstruction of the
      nasopharyngeal airway. These clinical assessments are particularly valid at the
      extremes of either marked obstruction or no obstruction. Clinical assessment
      alone may be insufficient to establish the presence of adenoidal obstruction, but
      clinical assessment alone when findings are unequivocally negative can suffice to
      rule out adenoidal obstruction with a high degree of confidence.

PMID- 9606224
TI  - Emergency department utilization by adolescents in the United States.
AB  - BACKGROUND: Adolescents in the United States have been shown to underutilize
      primary care services and therefore may rely heavily on emergency service.
      Although several small studies have explored local emergency services for youth,
      there are no published reports of adolescent utilization of emergency services on
      a national scale. Furthermore, emergency services data have not been aggregated
      according to the age subgroups used by the current guidelines for adolescent
      care. OBJECTIVE: To explore the utilization of emergency departments in the
      United States by early (11 to 14 years), middle (15 to 17 years), and late (18 to
      21 years) adolescent subgroups. DESIGN: Secondary analysis of the emergency
      department component of the 1994 National Hospital Ambulatory Medical Care
      Survey. SETTING: Nationally representative sample of 418 emergency departments in
      the United States. PATIENTS: Approximately 26,547 visits by patients of all ages,
      representing 93.4 million total visits in 1994 and 14.8 million adolescent
      visits. OUTCOME MEASURES: Number of visits, health insurance, reasons for visits,
      urgency of visits, resulting diagnoses, and hospitalization rates. RESULTS:
      Adolescents accounted for 15.4% of the population and 15.8% of emergency
      department visits in 1994. Late adolescents were overrepresented in emergency
      department visits relative to their population proportion (6.8% of visits, 5.3%
      of population), whereas early adolescents were underrepresented (4.6% of visits,
      5.9% of population). Lack of health insurance was more common among 11- to 21
      year-olds (26.2%) than either children (13.6%) or adults (22.7%). By ages 18 to
      21 years, 40.5% of male visits and 27.6% of female visits were uninsured. Injury
      related visits were more common among adolescents (28.6%) than either children
      (23.1%) or adults (18.2%). Injury was the leading reason for visits among all
      adolescent age-sex subgroups (36.6% to 42.0% of male visits and 14.1% to 27.2% of
      female visits) except females aged 18 to 21 years for whom digestive reasons
      ranked first (18.8%). Injury was the leading diagnosis for all adolescent age-sex
      subgroups, with peaks at early adolescence of 61.6% for males and 45.8% for
      females. Across all adolescent age-sex subgroups, 3.1% to 5.3% of visits resulted
      in hospitalization, and 41.0% to 52.5% of visits were urgent. These rates did not
      differ from those of children but were lower than those of adults. CONCLUSIONS:
      Utilization of emergency departments increases and health insurance decreases
      during adolescence, suggesting that adolescents with inadequate health insurance
      may rely heavily on emergency departments for their health care needs. Most
      adolescent visits to emergency departments are not urgent and might be better
      treated through nonemergency, primary care sites.

PMID- 9606225
TI  - Length of stay, jaundice, and hospital readmission.
AB  - OBJECTIVE: To evaluate the effect of postnatal age at the time of discharge on
      the risk of readmission to hospital with specific reference to readmission for
      hyperbilirubinemia. DESIGN: Case-control study based on chart review. SETTING:
      Large suburban community hospital in southeastern Michigan, delivering more than
      5000 infants annually. PATIENTS: Newborn infants, born between December 1, 1988,
      and November 30, 1994, who were readmitted to hospital within 14 days of
      discharge, were compared with a randomly selected control group who were not
      readmitted. RESULTS: Of 29,934 infants discharged, 247 (0.8%) were readmitted by
      the age of 14 days. One hundred twenty-seven (51%) were admitted because of
      hyperbilirubinemia and 74 (30%) with the diagnosis of "rule out sepsis." The
      factors associated with an increased risk of readmission to the hospital were:
      infant of diabetic mother [odds ratios (OR), 3.45; 95% confidence limits (CL),
      1.39 to 8.60]; gestation < or = 36 weeks (OR, 4.56; CL, 1.45 to 14.33), and 37
      1/7 to 38 weeks (OR, 2.95; CL, 1.63 to 5.35) versus > or = 40 weeks; presence of
      jaundice in the nursery (OR, 1.73; CL, 1.14 to 2.63); breastfeeding (OR, 1.78;
      CL, 1.13 to 2.81); male sex (OR, 1.58; CL, 1.07 to 2.34); length of stay < 48
      hours (OR, 1.91; CL, 1.15 to 3.16) and 48 to < 72 hours (OR, 2.09; CL, 1.25 to
      3.50) versus > or = 72 hours. Factors associated with readmission for jaundice
      were gestation < or = 36 weeks (OR, 13.2; CL, 2.70 to 64.6), 36 1/7 to 37 weeks
      (OR, 7.7; CL, 2.69 to 22.0), 37 1/7 to 38 weeks (OR, 7.2; CL, 3.05 to 16.97)
      versus > or = 40 weeks; jaundice during nursery stay (OR, 7.80; CL, 3.38 to
      18.0); length of stay < 48 hours (OR, 2.40; CL, 1.09 to 5.30) and 48 to < 72
      hours (OR, 3.15; CL, 1.40 to 7.09) versus > or = 72 hours; male sex (OR, 2.89;
      CL, 1.46 to 5.74); and breastfeeding (OR, 4.21; CL, 1.80 to 9.87). Infants whose
      length of stay was < 48 hours were at no greater risk for readmission for
      jaundice or other causes than those whose length of stay was > or = 48 hours to <
      72 hours. CONCLUSIONS: Discharge at any time < 72 hours significantly increases
      the risk for readmission to hospital and the risk for readmission with
      hyperbilirubinemia when compared with discharge after 72 hours. The American
      Academy of Pediatrics recommends that infants discharged < 48 hours should be
      seen by a health care professional within 2 to 3 days of discharge. Our
      observations, as well as those of others, suggest that this recommendation should
      also be extended to those discharged at < 72 hours after birth. One approach to
      decreasing the risk of morbidity and readmission, particularly from
      hyperbilirubinemia, would be to help mothers to nurse their infants more
      effectively from the moment of birth.

PMID- 9606226
TI  - Utilization of well-child care services for African-American infants in a low
      income community: results of a randomized, controlled case management/home
      visitation intervention.
AB  - OBJECTIVE: To evaluate a case management/home visitation intervention to improve
      access to and utilization of well-child care (WCC) visits. STUDY DESIGN:
      Randomized, controlled trial with baseline and follow-up interview surveys.
      Mothers and infants in the intervention group were assigned to a case manager who
      made at least four home visits during the infant's first year of life. In
      addition, the case managers contacted clients by telephone and mail to see if
      they had kept their WCC appointments and to follow up on other issues. SAMPLE AND
      DATA COLLECTION: A population-based random sample of African-American mothers of
      newborns from South Central Los Angeles: 185 mothers in the intervention group
      and 180 in the control group completed both interview surveys. The principal
      outcome variable was number of WCC visits. Additional outcome variables included
      the child's type of insurance, the number of months with insurance coverage
      during the first year of life, age when first enrolled in Medi-Cal, age at the
      first WCC visit, usual source of WCC, travel time to the usual source of care,
      whether the child had a regular provider, and whether the child ever needed care
      but did not get it. RESULTS: There was little change in the overall distribution
      of number of WCC visits during the first year of life. Comparisons of the
      cumulative numbers of visits for each possible cutoff showed that children in the
      intervention group were more likely than children in the control group to have at
      least four visits (81% vs 70%). Because this split was identified empirically
      rather than through an antecedent hypothesis, we conducted a Smirnov test to
      account for multiple comparisons. This test showed a reduced level of
      significance. Other outcome variables did not show significant differences for
      the control and intervention groups. CONCLUSIONS: In light of the high expense of
      this intervention, our evaluation shows that our moderate-intensity case
      management and home visitation program is not an effective way to increase the
      number of WCC visits.

PMID- 9606227
TI  - Comparison of two strategies for surfactant prophylaxis in very premature
      infants: a multicenter randomized trial.
AB  - INTRODUCTION: Previous trials of surfactant therapy in premature infants have
      demonstrated a survival advantage associated with prophylactic therapy as an
      immediate bolus, compared with the rescue treatment of established respiratory
      distress syndrome. The optimal strategy for prophylactic therapy, however,
      remains controversial. When administered as an endotracheal bolus immediately
      after delivery, surfactant mixes with the absorbing fetal lung fluid and may
      reach the alveoli before the onset of lung injury. This approach, however, causes
      a brief delay in the initiation of standard neonatal resuscitation, including
      positive pressure ventilation, and is associated with a risk for surfactant
      delivery into the right main stem bronchus or esophagus. As an alternative
      approach, surfactant prophylaxis may be administered in small aliquots soon after
      resuscitation and confirmation of endotracheal tube position. Although this
      strategy has substantial logistical advantages in clinical practice, its efficacy
      has not been established. OBJECTIVE: The purpose of this study was to determine
      whether the established benefits of the immediate bolus strategy for surfactant
      prophylaxis could still be achieved using a postventilatory aliquot strategy
      after initial standard resuscitation and stabilization. DESIGN: Multicenter
      randomized clinical trial with patients randomized before delivery to immediate
      bolus or postventilatory aliquot therapy. PARTICIPANTS: Inborn premature infants
      delivered to mothers at an estimated gestational age of 24[0/7] to 28[6/7] weeks.
      INTERVENTIONS: Those infants who were randomized to the immediate bolus strategy
      were intubated as rapidly as possible after birth, and a 3-mL intratracheal bolus
      of calf lung surfactant extract (Infasurf) was administered before the initiation
      of positive pressure ventilation. Those infants who were randomized to the
      postventilatory aliquot strategy received standard resuscitation measures with
      intubation by 5 minutes of age, if not required earlier. At 10 minutes after
      birth, 3 mL of surfactant was administered in 4 divided aliquots of 0.75 mL each.
      Patients in both groups were eligible to receive up to three additional doses of
      surfactant as rescue therapy in the neonatal intensive care unit, if needed.
      OUTCOME MEASURES: The primary outcome variable was survival to discharge to home.
      Secondary variables included neonatal complications and requirement for oxygen
      therapy at 36 weeks' postmenstrual age. RESULTS: Among three centers, 651 infants
      were enrolled and randomized before delivery. Survival to discharge to home was
      similar for the two strategies for surfactant therapy as prophylaxis: 76% for the
      immediate bolus group and 80% for the postventilatory aliquot group. In a
      secondary analysis, the rate of supplemental oxygen administration at 36 weeks'
      postmenstrual age was 18% for the immediate bolus group and 13% for the
      postventilatory aliquot group. CONCLUSIONS: Survival to discharge to home was
      similar with immediate bolus and postventilatory aliquot strategies for
      surfactant prophylaxis. Because of its logistical advantages in the delivery room
      and its beneficial effects on prolonged oxygen requirements, we recommend the
      postventilatory aliquot strategy for surfactant prophylaxis of premature infants
      delivered before 29 weeks' gestation.

PMID- 9606228
TI  - Incidence and prevalence of neutralizing antibodies to the common adenoviruses in
      children with cystic fibrosis: implication for gene therapy with adenovirus
      vectors.
AB  - OBJECTIVE: Defining the infection rate and prevalence of the common adenoviruses
      (Ads) in cystic fibrosis (CF) children may aid in formulation of strategies for
      gene therapy with Ad vectors. We undertook this study to determine the incidence
      and prevalence of infection with the common Ads in children with CF. METHODOLOGY:
      Thirty newly diagnosed CF children mean age 1.1 years (Group 1), 48 CF children
      mean age 4.6 years (Group 2), and 47 mothers of CF children (Group 3) were
      followed for a mean of 13 months. Group 4 consisted of 33 adult volunteers seen
      once. Throat and stool specimens for virus culture, and blood samples were
      obtained every 3 months from CF children in Group 1. Blood samples from CF
      children (Group 2) and their mothers (Group 3) were obtained every 6 months, and
      once from adults in Group 4. Neutralizing antibody to Ad serotypes 1 through 7
      (Ad 1 to Ad 7) was evaluated with a microneutralization assay. RESULTS: Five
      (16.7%) CF children in Group 1 were culture-positive for an Ad; 4 of these CF
      children developed a fourfold or greater rise in antibody titer. Ad 3 infection
      occurred frequently based on serology; seronegative (< 3.5 log 2) CF children had
      a higher infection rate compared with seropositive CF children (7/11 vs 1/34).
      The prevalence of neutralizing antibodies in CF children in order of decreasing
      frequency was 91.1% to Ad 3, 37.5% to Ad 2, 27.1% to Ad 1, 26.1% to Ad 7, 16.7%
      to Ad 5, 8.5% to Ad 4, and 2.0% to Ad 6. The neutralizing antibody titers in
      seropositive CF children were comparable to those in adults except to Ad 3, which
      was significantly greater in mothers of CF children. CONCLUSIONS: CF children had
      a normal antibody response after Ad infection, preexisting antibody may protect
      against reinfection and antibody prevalence was low to the common Ads.

PMID- 9606229
TI  - Comparison of cost and clinical outcome between transcatheter coil occlusion and
      surgical closure of isolated patent ductus arteriosus.
AB  - OBJECTIVE: The objective of this study was to compare the cost (measured as
      resource utilization by the institution) and clinical effectiveness of
      transcatheter coil occlusion and surgical patent ductus arteriosus (PDA) closure.
      Similar comparisons have been made previously with other devices no longer in use
      in the United States. No such comparison has been made for coil occlusion, which
      has been performed increasingly since 1992. METHODS: All patients who underwent
      either coil or surgical closure of uncomplicated PDA at our institution between
      August 1993 and June 1996 were retrospectively identified. Patients were included
      in the study if they were eligible for either closure technique. Thus, they had a
      restrictive PDA (not associated with pulmonary hypertension) and no overt
      evidence of congestive heart failure. Patients were excluded if they had other
      significant cardiac or noncardiac problems. Total procedural and recovery costs
      (including labor, material, equipment, and overhead) incurred by the provider
      were determined using a cost accounting system called Transition Systems, Inc. To
      define further how costs differed for the two techniques, total costs were
      subdivided into the categories of professional, technical, inpatient hospital
      stay, postprocedure testing, and supplies and other miscellaneous costs. PDA
      closure rates and associated complications also were compared. Follow-up
      information was sought from outpatient visits to our institution or by contacting
      the referring physicians. RESULTS: A total of 39 patients were identified, 3 of
      whom were excluded because of coexisting medical problems. The study group
      consisted of 36 patients; 24 underwent PDA coil occlusion and 12 surgical
      closure. Mean age and weight were 8.8 years and 28.5 kg for the coil patients,
      and 7.3 years and 32.8 kg for the surgical patients. Median procedural duration
      was 150 minutes for the coil group and 165 minutes for the surgical group. The
      total cost to the institution of coil occlusion was significantly lower than that
      of surgical closure ($5273 vs $8509). The largest difference lay in the cost of
      hospital stay ($398 vs $2566) and in the professional costs ($1506 vs $2782).
      Technical costs were similar ($2156 for coil, $2151 for surgery), although use of
      the catheterization laboratory per unit of time was more expensive than use of
      the operating room ($800 vs $400 per hour). Additional technical costs of the
      surgical procedure related to general anesthesia and postoperative care made up
      the difference. No patient in either group had a residual PDA murmur at hospital
      discharge or thereafter. Follow-up echocardiography was performed in all coil
      occlusion patients, and tiny residual leaks were detected in 17%. Only 42% of the
      surgical patients had postoperative echocardiography; none had residual leaks.
      There were no deaths or major complications in either group. CONCLUSIONS:
      Transcatheter coil occlusion is as effective and less costly than surgical
      closure if silent residual leaks are not considered clinically significant. This
      information may be used increasingly in patient care decisions in the current era
      of managed medical care.

PMID- 9606230
TI  - Implications for estimates of disability in children: a comparison of
      definitional components.
AB  - OBJECTIVE: To test how prevalence estimates and characteristics of children vary
      by the way that disability is defined. Specifically, to determine 1) the
      proportions of children identified as disabled by one particular
      operationalization of disability based on parental reports of three types of
      consequences (i.e., functional limitations [FL]), dependence on compensatory
      mechanisms (CD), and service use or need beyond routine [SU/N]), and 2) whether
      children identified as disabled by these three types of consequences differ by
      type of disorder or condition, age, socioeconomic status, or race. METHOD: We
      analyzed a national dataset representing a random sample of 712 households with
      1388 children. The Questionnaire for Identifying Children with Chronic Conditions
      (QuICCC) was used to identify children with disabling conditions. We divided the
      QuICCC items into three discrete sets, reflecting three definitional components
      of disability, and compared the proportions and characteristics of children
      fitting these components separately and in combination. RESULTS: Using the QuICCC
      definition of disability, SU/N identified the largest proportion of children
      (72%), followed by CD (55%) and FLs (49%). Forty-four percent of children were
      identified by only one component, 36% by two components in any combination, and
      20% by all three components. The type of disorder or condition generally did not
      vary by the three definitional components, although the FL component may be more
      effective at identifying children with sensory impairments. Children identified
      by two or more components were more likely to have multiple conditions and had
      more pervasive disorders than those identified by only one component. The
      youngest children (0 to 3 years old) may be less likely to be identified as
      disabled than children of other ages, especially by FLs. FLs also were more
      likely to identify children from the poorest and least educated families.
      CONCLUSIONS: Although the specific findings reported here pertain to a single
      definitional approach (the QuICCC), the data highlight that who will be
      classified as disabled (and who will not) may be dependent on how disability is
      defined. The implications of using different definitions and definitional
      components on both the prevalence and the characteristics of children with
      disabilities need to be considered before data can be applied responsibly and
      appropriately.

PMID- 9606231
TI  - Pitfalls in the diagnosis of ventricular shunt dysfunction: radiology reports and
      ventricular size.
AB  - INTRODUCTION: The diagnosis of shunt malfunction can be difficult even for the
      experienced clinician and may lead to disastrous circumstances when
      misinterpreted. Less experienced physicians may rely more on radiographic reports
      as a primary diagnostic modality. In this study, we evaluated the reliability of
      using these reports without accurate clinical assessment. METHODS: All shunt
      revisions seen at Children's Hospital (Birmingham, AL) between January 1996 and
      August 1996 were reviewed, excluding patients with brain tumors, supratentorial
      extraaxial fluid collections, and infections. Sixty-eight patients underwent 100
      operations for shunt malfunction. All patients had evidence of shunt blockage,
      disconnection, catheter malposition, or valve pressure incompatibility. The
      prospective radiographic interpretation of preoperative computed tomography and
      magnetic resonance imaging scans was reviewed in each case. RESULTS: Twenty-four
      percent of the reports made no mention of shunt malfunction. In this group, the
      ventricular system was described as "unchanged," "stable," "normal,"
      "unremarkable," "small," "smaller," "slit," "negative," and "no hydrocephalus,"
      with no other comment to support a diagnosis of shunt malfunction. An additional
      9% of reports contained the same terms, while also hinting at some other clinical
      or radiographic data that suggest the possibility of shunt failure (e.g., a shunt
      disconnection seen on plain radiographs), despite the scan findings. In all
      patients in this group, symptoms improved after surgery. CONCLUSION: We conclude
      that as many as one third of patients presenting with shunt malfunction will not
      have the diagnosis of shunt malfunction supported by a prospective radiologic
      interpretation of brain imaging. Although the neurosurgical community can assess
      the clinical situation to determine the need for surgery, other clinicians can be
      easily reassured by a radiographic report that does not mention or diagnose shunt
      malfunction. Today, more than ever, nonneurosurgeons are being called on to
      evaluate complex clinical situations and may rely on radiographic reports.

PMID- 9606232
TI  - Outcome prediction in Greek neonatal intensive care units using a score for
      neonatal acute physiology (SNAP)
AB  - OBJECTIVES: This study was undertaken to evaluate the performance of the score
      for neonatal acute physiology (SNAP) in Greece, to examine the predictive power
      of SNAP calculated during the 12 hours after admission in comparison with
      customarily calculated SNAP during the first 24 hours, and to assess SNAP during
      the second 12 hours from admission as a measure of response to treatment.
      METHODOLOGY: A total of 579 newborns admitted to three neonatal intensive care
      units (NICUs) from two cities in Greece were enrolled in the study; SNAP was
      determined during the first 12 hours, the second 12 hours, and the first 24 hours
      from admission to the NICU and calculated using an algorithm based on deviations
      from normal values of 26 physiologic parameters. RESULTS: All three variants of
      SNAP were powerful predictors of vital status at discharge, as well as of
      duration of stay among survivors. A five-point increase in SNAP in the first 12
      hours corresponds to a more than twofold ratio in the odds for death, whereas a
      five-unit difference in SNAP from the second 12 hours corresponds to a more than
      threefold ratio. The combined 24-hour score was similar to that for the first 12
      hours. A considerable advantage of SNAP was its independence from more
      traditional predictors of neonatal death, notably gestational age, birth weight,
      and Apgar score. The combination of all of these predictors improved further the
      overall predictive potential. CONCLUSIONS: SNAP is a useful tool in medical
      research and can be applied in different population groups. Its independence from
      birth weight underlines its added value to predict fatality ratios. Moreover, the
      results of the present study indicate that SNAP can be estimated without loss of
      predictive efficiency during the first 12 hours from admission to the NICU,
      whereas SNAP during the second 12 hours adequately reflects the effectiveness of
      early medical interventions.

PMID- 9606233
TI  - Baclofen overdose: drug experimentation in a group of adolescents.
AB  - BACKGROUND: Baclofen, a lipophilic analog of gamma-aminobutyric acid, is
      clinically used to control spasticity. We report a mass exposure to baclofen in
      adolescents seeking intoxication; toxicokinetic data are included. CASE SERIES: A
      group of adolescents became symptomatic after ingesting 3 to 30 20-mg tablets of
      baclofen during a party at a suburban Boys' Club. Several children were noted to
      be very lethargic by chaperones, ingestion was suspected, and paramedics were
      called. Some white tablets were found in a couch at the site of the party. The
      Massachusetts Poison Control Center was called, and the tablets were identified
      as baclofen (20 mg). Fourteen patients were taken to local hospitals; 9 required
      intubation. Eight adolescents were transferred to our institution. In these 8
      patients, symptoms were noted within 1 to 2 hours after overdose. The most common
      clinical findings included coma (7), hypothermia (6), bradycardia (5),
      hypertension (4), and hyporeflexia (8). Mean length of mechanical ventilation was
      40 hours. Three patients had unifocal premature ventricular contractions. Two
      patients had tonic-clonic seizures. A single dose of activated charcoal was given
      to all patients. Drugs administered included nifedipine (1), flumazenil (1),
      naloxone (1), lorazepam (2), and phosphenytion (2). All patients recovered and
      were discharged home within 5 days of ingestion. Serial serum baclofen levels
      were obtained in all intubated patients (range, 0.049 to 6.0; normal, 0.08 to .40
      microgram/mL). Levels obtained 14 hours after ingestion showed a linear
      correlation with length of mechanical ventilation (R2 = 0.9863). Persistent
      symptoms were noted in some patients, despite nondetectable baclofen levels.
      Toxicologic screening for drugs of abuse was negative except in 2 patients with
      ethanol levels, both < 5 mg/dL. CONCLUSION: Baclofen overdose may result in coma,
      apnea, autonomic disturbances, cardiac conduction abnormalities, and seizures.
      Levels obtained shortly after overdose correlate with length of mechanical
      ventilation.

PMID- 9606234
TI  - The potential benefits of the pediatric nonheartbeating organ donor.
AB  - OBJECTIVE: To examine the population of the pediatric intensive care unit in a
      large children's hospital to determine the potential importance of pediatric
      nonheartbeating organ donors (NHBDs). STUDY DESIGN: We analyzed retrospectively
      the 6307 admissions to the pediatric intensive care unit at the Children's
      Hospital of Philadelphia from January 1992 to July 1996 to identify all deaths.
      The hospital records of the children who had died were then reviewed to determine
      the mode of death, organ donation rate of heartbeating donors, and the number of
      potential NHBDs. Criteria for the NHBD included the decision to forgo life
      sustaining therapy, death occurring within 2 hours of withdrawal of life support,
      and the absence of sepsis, HIV, hepatitis, or extracranial malignancy. RESULTS:
      Of 319 deaths, 102 (32.0%) died with resuscitation, 84 (26.3%) were brain-dead,
      111 (34.8%) had withdrawal of life support, and 22 (6.9%) were on do-not
      resuscitate orders. Of the 84 brain-dead children, 74 (88.1%) were medically
      suitable heartbeating donors, and 43 (58.1%) donated organs. Of the 111 patients
      who had life support withdrawn, 31 (27.9%) qualified for NHBDs. CONCLUSIONS: The
      routine use of the NHBD has the potential to increase organ donation at our
      institution by 42%. We discuss the ethical issues relating to NHBDs required to
      properly include these patients as potential organ donors.

PMID- 9606235
TI  - Proarrhythmia associated with cisapride in children.
AB  - BACKGROUND: Cisapride is a prokinetic agent that facilitates gastrointestinal
      motility and is widely used for the treatment of gastroesophageal reflux disease
      (GERD) in adults and children. However, reports of ventricular proarrhythmia have
      been noted in patients taking cisapride, particularly in conjunction with other
      drugs that may inhibit hepatic metabolism of cisapride via the cytochrome P450
      3A4 system. OBJECTIVE: We designed a prospective, blinded study to evaluate the
      effect of cisapride on ventricular repolarization in children with GERD. METHODS:
      We analyzed the electrocardiograms (ECGs) from 35 children (age 0.4 to 18 years,
      mean 5.2 years) including measurement of the resting QT interval (QTc), JT
      interval (JTc), as well as QT and JT interlead dispersion markers. Data from
      these patients were compared with ECGs from a control group of 1000 normal
      children. RESULTS: Eleven (31%) of 35 patients receiving cisapride had a
      prolonged QTc (> or = 450 ms). The JTc was prolonged > or = 360 ms in 16 of 35
      patients (46%). The mean QTc in the cisapride group was 428 +/- 35 ms and mean
      JTc was 336 +/- 35 ms. An increased QT or JT dispersion (> 70 ms) was seen in
      only 3 of 35 children. Of the 11 children with QTc prolongation, 2 had documented
      torsades de pointes ventricular tachycardia. Both patients were taking cisapride
      concomitantly with a macrolide antibiotic. All other patients were treated with
      either cisapride alone or in conjunction with other GERD agents, such as
      ranitidine or omeprazole. CONCLUSIONS: Cisapride may cause prolongation of
      ventricular repolarization in children. There does not appear to be increased
      heterogeneity of repolarization or delayed depolarization in this small sample.
      The proarrhythmia may be exacerbated by medications that inhibit cytochrome P450
      3A4 hepatic metabolism, overdosage, or mechanisms that result in decreased serum
      clearance. ECG intervals should be monitored in children maintained on cisapride,
      particularly when used in combination with other known QT-prolonging medications.

PMID- 9606236
TI  - Prevention of sports injuries.

PMID- 9606237
TI  - Outcome prediction in Greek neonatal intensive care units.

PMID- 9606238
TI  - Cystic fibrosis: when should high-resolution computed tomography of the chest be
      obtained?

PMID- 9606239
TI  - Screening for Elevated Blood Lead Levels.

PMID- 9606240
TI  - Neonatal Drug Withdrawal.

PMID- 9606241
TI  - Facilities and Equipment for Care of Pediatric Patients in a Community Hospital.

PMID- 9606244
TI  - The Internet as a source for current patient information.
AB  - OBJECTIVE: The purpose of this study was to assess the quality of information a
      lay person could obtain from Internet (Net) sources regarding the treatment of
      childhood diarrhea. It also afforded an opportunity to evaluate the awareness and
      compliance of the general medical community with the American Academy of
      Pediatrics (AAP) guidelines on the management of acute diarrhea. METHODS: This
      was a prospective, open, observational, literature review performed with a
      computer workstation and medical library. The AAP practice parameter on the
      management of acute gastroenteritis in young children was selected as the current
      standard by which to judge all other documents. The Net was searched, and all
      documents retrievable from the first 300 references were evaluated for compliance
      with current recommendations on the management of diarrhea in children. RESULTS:
      Of 60 articles published by traditional medical sources, only 12 (20%) conformed
      to current AAP recommendations for treatment of children. The source of the
      information, even if from a major academic medical center, did not improve the
      likelihood of compliance. CONCLUSIONS: As demonstrated by information supplied on
      World Wide Web sites by traditional medical sources, recommendations for the
      treatment of acute diarrhea show a low percentage of concurrence with the AAP
      guidelines. Major medical institutions, schools, and hospitals need to devise
      ways to carefully monitor and establish quality control of what is being
      distributed from their home pages. Patients must be warned about the voluminous
      misinformation available on medical subjects on the Net.

PMID- 9606243
TI  - Screening for urinary tract infection in infants in the emergency department:
      which test is best?
AB  - OBJECTIVE: Comparison of rapid tests and screening strategies for detecting
      urinary tract infection (UTI) in infants. METHODS: Cross-sectional study
      conducted in an urban tertiary care children's hospital emergency department and
      clinical laboratories of 3873 infants <2 years of age who had a urine culture
      obtained in the emergency department by urethral catheterization; results of
      urine dipstick tests for leukocyte esterase or nitrites, enhanced urinalysis (UA)
      (urine white blood cell count/mm3 plus Gram stain), Gram stain alone, and
      dipstick plus microscopic UA (white blood cells and bacteria per high-powered
      field) compared with urine culture results (positive urine results defined as
      >/=10 colony-forming units per milliliter of urinary tract pathogen) for each
      sample. Cost comparison of 1) dipstick plus culture of all urine specimens versus
      2) cell count +/- Gram stain of urine, culture only those with positive results.
      RESULTS: The enhanced UA was most sensitive at detecting UTI (94%; 95% confidence
      interval: 83,99), but had more false-positive results (16%) than the urine
      dipstick or Gram stain (3%). The most cost-effective strategy was to perform
      cultures on all infants and begin presumptive treatment on those whose dipstick
      had at least moderate (+2) leukocyte esterase or positive nitrite at a cost of
      $3.70 per child. With this strategy, all infants with UTI were detected. If the
      enhanced UA was used to screen for when to send the urine for culture, 82% of
      cultures would be eliminated, but 4% to 6% of infants with UTI would be missed
      and the cost would be higher ($6.66 per child). CONCLUSION: No rapid test can
      detect all infants with UTI. Physicians should send urine for culture from all
      infants and begin presumptive treatment only on those with a significantly
      positive dipstick result. The enhanced UA is most sensitive for detecting UTI,
      but is less specific and more costly, and should be reserved for the neonate for
      whom a UTI should not be missed at first visit.

PMID- 9606245
TI  - Childhood drownings and fencing of outdoor pools in the United States, 1994.
AB  - OBJECTIVES: To determine the prevalence of proper fencing around outdoor swimming
      pools among US households and to describe this fencing in relation to demographic
      and other household factors. To estimate the number of drownings among children
      <5 years of age that might be prevented by having proper fencing around all
      residential pools in the United States. METHODS: A 1994, randomly dialed national
      telephone survey contacted 5238 adults who reported demographic information and
      household characteristics including whether the household had an outdoor swimming
      pool and the fencing around the pool. Data were weighted to obtain national
      estimates and percentages. The number of preventable drownings was estimated with
      a population-attributable risk equation. RESULTS: Approximately 18.5 million
      American households owned or had access to an outdoor swimming pool in 1994, and
      76% (13.9 million) of them appeared to have had adequate fencing. Adequate
      fencing was associated with household income and type of home. We estimate that
      19% of pool-related drownings among children <5 years of age in 1994 (88
      drownings) might have been prevented if all residential pools in the United
      States were properly fenced. CONCLUSIONS: Adequate pool fencing prevents a child
      from having access to a swimming pool if a responsible adult is not present and
      has been promoted as a method to prevent drowning. Our research suggests that
      even if all residential pools in the United States were properly fenced, most
      drownings among children <5 years of age would not be prevented. Thus, additional
      strategies to prevent drowning will be needed.

PMID- 9606246
TI  - Childhood caffeine tic syndrome.
AB  - OBJECTIVE: To determine whether caffeine ingestion was temporally correlated with
      tics in 2 healthy children. METHODS: Two first-degree cousins were observed over
      a period of approximately 3 years, and the presence and absence of tics was
      recorded and correlated with consumption of or abstinence from caffeinated foods
      or beverages. RESULTS: Appearance and disappearance of tics were closely and
      clearly temporally correlated with ingestion and elimination of caffeine in the
      cousins' diets. CONCLUSIONS: Our observations suggest that caffeine may
      precipitate tics in susceptible children.

PMID- 9606247
TI  - Circumcision practice patterns in the United States.
AB  - OBJECTIVE: To determine 1) the performing of circumcision by medical specialty,
      gender, and years of practice; 2) the pattern of anesthetic use for this
      procedure; and 3) the reasons physicians cite for not using anesthesia. DESIGN: A
      total of 3066 questionnaires were received from a mailing to a representative
      sampling of physicians stratified by specialty and geographic location. RESULTS:
      Fifty-eight percent (1768) of the questionnaires were returned and interpretable
      from the following specialists: pediatricians (PEDs), 73% (n = 691); family
      practitioners (FPs), 52% (n = 464); and obstetricians (OBs), 51% (n = 623). Of
      the respondents, 956 (54%) perform at least one circumcision per month (35% of
      PEDs; 60% of FPs; 70% of OBs). Of the physicians performing circumcisions, 45%
      use anesthesia (71% of PEDs; 56% of FPs; 25% of OBs). Of physicians using
      anesthesia, 85% use dorsal penile nerve block. A significantly higher percentage
      of male physicians (57%) are performing circumcisions than are females (45%), but
      there was no difference in the percent using anesthesia. Recently trained PEDs
      and FPs were more likely to use anesthetics than were their older colleagues, but
      OB use of pain relief was independent of their practice longevity. Physicians in
      the western states were significantly more likely to use anesthesia than were
      other physicians from the rest of the United States. Respondents who did not use
      anesthesia cited "concern over adverse drug effects" (54%) followed by "procedure
      does not warrant anesthesia" (44%) as the most common explanations. CONCLUSIONS:
      A substantial number of PEDs are performing circumcisions, and they are most
      likely to use anesthesia (71%), followed by FPs (56%), then OBs (25%). With
      recent recognition of the importance of pain reduction in neonatal procedures and
      the lack of substantiated contraindications to newborn anesthetic use, additional
      education of current practitioners, residents, and parents is required to
      increase the use of anesthesia for circumcision.

PMID- 9606249
TI  - Magnetic resonance imaging and spectroscopy of regional brain structure in a 10
      year-old boy with elevated blood lead levels.
AB  - OBJECTIVE: The effects of elevated blood lead levels on the development of
      children have been examined only in the context of behavioral and
      neuropsychological evaluations. No studies have examined the effects of lead on
      brain metabolism in vivo or on structural and/or functional correlates of brain
      function in children. In the human brain, magnetic resonance spectroscopy (MRS)
      provides a noninvasive, risk-free method to monitor the biochemistry of acute and
      chronic stages of disease. The purpose of this study was to examine in vivo the
      use of MRS for the evaluation of the neurotoxic effects of lead on the nervous
      system, by detection of brain metabolism, especially N-acetylaspartate, a
      metabolite shown to decrease in processes that involve neuronal loss.
      METHODOLOGY: Two male cousins who live in the same household and share the same
      socioeconomic background and home environment were studied. The subject, a 10
      year-old boy, had elevated blood lead levels. His cousin, a 9-year-old boy, was
      not exposed to lead. Both underwent a comprehensive neuropsychological evaluation
      and both were evaluated using the magnetic resonance imaging (MRI) and MRS at the
      University of Pennsylvania Medical Center. High-resolution MRI and MRS were
      performed using a 3-in surface coil. Localized proton spectra were obtained from
      contiguous 6 x 6 x 10-mm voxels using one-dimensional phase encoding, with a 2000
      millisecond repetition time and a 31-millisecond echo time. RESULTS:
      Neuropsychological evaluation demonstrated areas of impairment in the lead
      exposed child, including difficulties in academic skills of reading, writing, and
      arithmetic, as well as deficient linguistic skills and attentional mechanism. By
      contrast, studies of the cousin, who was not exposed to lead, showed overall
      neuropsychological functioning within normal limits. Although both children had a
      normal MRI examination of the brain, studies of the lead-exposed boy showed a
      significant alteration in brain metabolites, with a reduction in the N
      acetylaspartate:creatine ratio for both gray and white matter on the MRS
      examination, compared with his cousin. CONCLUSIONS: The present study is a first
      attempt to determine in vivo metabolic differences in the brain of a child
      exposed to lead compared with a healthy control subject. This is a unique case
      because these children were matched on a number of variables usually regarded as
      confounders in behavioral lead studies, and therefore can be regarded as matched
      controls. The present study demonstrates that MRS is a feasible, noninvasive
      technique for in vivo examination of the brains of children exposed to lead. We
      were able to obtain high-quality spectra from voxels as small as 0.36 cm at 1.5T.
      The spatial resolution used in the present study is sufficient to obtain spectra
      from voxels almost exclusively composed of gray matter. The one-dimensional phase
      encoding approach used presents the advantage of obtaining several spectra
      simultaneously in a relatively short time. The present study has allowed us to
      examine the spectroscopic patterns of frontal gray and white matter after lead
      exposure relative to the normal pattern seen in healthy children and adults. The
      MRS study of the healthy, nonlead-exposed cousin demonstrated spectra entirely
      consistent with the spectral pattern reported in previous studies of healthy
      individuals. By contrast, the spectra obtained from the lead-exposed child
      deviated from the expected pattern in all metabolite ratios analyzed. Because N
      acetylaspartate has been shown as a measure of neuronal viability, the level of N
      acetylaspartate may enable us to evaluate the degree of neuronal loss in children
      exposed to lead. The MRI examination indicated no structural abnormalities or
      cortical thinning, and no abnormal findings in either case. By contrast, MRS
      indicated a significant change from normal values for the lead-exposed child.
      This supports the idea that lead neurodevelopmental toxicity may be related to
      inter

PMID- 9606248
TI  - Telephone call reminders and attendance in an adolescent clinic.
AB  - OBJECTIVE: To determine the effect of a single telephone call reminder on
      appointment compliance among adolescents in an inner city, hospital-based clinic.
      METHODS: A randomized clinical trial was conducted at the Adolescent Clinic, a
      part of the Ambulatory Pediatric Practice Clinic in Cleveland, Ohio, from
      December 1995 to November 1996. A total of 703 routine adolescent ambulatory
      appointments were randomized to receive either a single telephone call reminder 1
      day before the appointment or to receive no reminder. A single telephone call
      attempt was directed primarily to the parent or guardian of the patient in the
      assignment group. If not available, the reminder message was left with the
      patient or other family member, or on the answering machine. The study variables
      selected included age, gender, appointment time, distance from clinic, and
      payment source, and for the intervention group, the recipient of the reminder
      telephone call. The outcome measure was the attendance rate. RESULTS: The
      intervention group (n = 347) and control group (n = 356) were well balanced for
      all study variables. The overall attendance rate was 49.8%. Only 204 (58.8%) of
      the 347 attempted intervention appointments were contacted successfully by
      telephone. In the attempted intervention analysis, the attendance rate of 55.6%
      in the intervention group (n = 347), regardless of whether subjects were
      successfully contacted by telephone, was 26.1% greater than the 44.1% attendance
      rate in the control group. In the completed intervention analysis, the attendance
      rate of 65.2% in the successfully contacted individuals within the intervention
      group (n = 204) was increased by 47.8% over that in the control group. In the
      univariate analysis, attendance for self-paying patients (25.4%) was worse than
      that for any group. In the logistic regression analysis, both the reminder
      telephone call intervention and the payment source were independent predictors of
      attendance. In the group that was called successfully (n = 204), there was no
      association between attendance and the recipient of the telephone call.
      CONCLUSIONS: Telephone reminders are a very effective method of increasing
      attendance in a hospital-based adolescent clinic. The reminder is a consistently
      effective intervention whether the message is delivered to the patient, to the
      parent or other family member, or to a telephone answering machine. Adolescent
      patients whose visits are not covered by Medicaid or commercial insurance are
      least likely to attend their clinic appointments, and a telephone call reminder
      has no effect on this pattern.

PMID- 9606250
TI  - Ifosfamide-induced nephrotoxicity in children: critical review of predictive risk
      factors.
AB  - Ifosfamide is widely used in the treatment of pediatric solid tumors. Its main
      adverse effects are various forms of renal tubular and glomerular damage. Many
      risk factors have been proposed to play a role in the development and severity of
      nephrotoxicity in children receiving ifosfamide, among which are 1) patient's
      age, 2) cumulative ifosfamide dose, 3) concurrent administration of cis or
      carboplatinum, 4) unilateral nephrectomy, and 5) method of ifosfamide
      administration. However, presently there is no consensus regarding the weight of
      each one of them. Therefore, we critically reviewed the major studies that have
      evaluated the different risk factors in an attempt to determine the relative
      importance of each. Cumulative ifosfamide doses of >/=60 g/m appears to be the
      most consistent independent predictor for both the development and the severity
      of nephrotoxicity, whereas a younger age (<5 years of age) was associated
      primarily with the more severe and chronic forms of proximal tubulopathy.
      Comparable incidence and severity forms of proximal tubulopathy among children
      who had been treated with cis platinum in addition to ifosfamide and those who
      had not indicate that platinums probably potentiate ifosfamide-induced renal
      damage rather than act as a major independent risk factor. Finally, although
      unilateral nephrectomy has been proposed as a significant risk factor in
      different studies, the relatively small number of nephrectomized children in
      these cohorts limit the strength of this association. To reduce the frequency and
      severity of ifosfamide-induced nephrotoxicity, it appears that cumulative doses
      of 60 g/m should be considered carefully, especially in children <5 years of age.

PMID- 9606251
TI  - Periorbital vasculitis complicating Kawasaki syndrome in an infant.
AB  - Periorbital vasculitis is a previously unreported complication of Kawasaki
      syndrome (KS). We describe an infant with severe KS refractory to initial
      management with salicylate and intravenous immunoglobulin (IVIG). Retreatment
      with IVIG and high-dose pulsed steroids was required for persistent fever and
      inflammatory manifestations. Despite aggressive medical therapy, a large left
      coronary artery aneurysm developed. After apparent complete KS remission, acute
      periorbital vasculitis developed in the left upper eyelid and orbit, requiring
      operative intervention for diagnosis and high-dose pulsed steroids for therapy.
      The significance of this previously unreported ophthalmic complication of KS is
      reviewed, along with a discussion of the role of steroids in KS manifestations
      refractory to IVIG.

PMID- 9606252
TI  - Brief approaches to educating patients and parents in primary care.
AB  - PURPOSE: Pediatricians are encouraged by the American Academy of Pediatrics and
      Bright Futures guidelines to use well-child care as an opportunity to promote
      learning and development, encourage positive parenting practices, help children
      acquire behavioral self-control, and enhance the well-being of children and their
      families. Such counseling can consume considerable provider time. In an era of
      dwindling resources for health care, there is pressure to deliver services as
      efficiently and effectively as possible. Thus, the purpose of this article is to
      view methods for patient and parent education that are not only effective but
      also brief. DESIGN: Review of 114 articles on issues relevant to patient
      education. RESULTS AND CONCLUSIONS: Parents appear to respond best to information
      that focuses on their specific area of concern. Media, such as advertising
      campaigns or office posters, can be helpful for broadening parents' range of
      interests. In response, verbal suggestions are effective for conveying brief,
      concrete information when parents are not stressed. Written information should be
      added for addressing more complex issues. Modeling and role-playing appear
      especially useful when confronted with problematic parenting or child behavior.
      These approaches, if selected wisely and applied well, offer families needed
      assistance that has proven effectiveness in improving children's and families'
      health and well-being.

PMID- 9606253
TI  - Racial/ethnic differences in the decision to breastfeed among adolescent mothers.
AB  - OBJECTIVE: To identify racial/ethnic differences in prevalence and the factors
      that influence decisions to breastfeed among adolescent mothers. METHODS: A total
      of 696 Mexican-American, African-American, and Caucasian adolescent mothers </=18
      years of age were interviewed on the postpartum ward of university hospital
      within 48 hours of delivery. Self-reported factors associated with the decision
      to breastfeed were assessed. RESULTS: The decision to breastfeed was reported by
      55% of Mexican-American, 45% of Caucasian, and 15% of African-American adolescent
      mothers. With the exception of perceived benefits of breastfeeding and exposure
      to educational materials, most factors associated with breastfeeding differed by
      race/ethnicity. Among Mexican-Americans, important factors included having relied
      on feeding advice (adjusted odds ratio [AOR] = 7.6); the feeding preference of a
      partner (AOR = 7.0) or mother (AOR = 6. 6); and feeding decisions made in early
      pregnancy (AOR = 4.7). Among African-Americans, important factors included living
      with a partner (AOR = 10.6); having a mother who breastfed (AOR = 5.9); the
      feeding preference of a partner (AOR = 5.6) or health care provider (AOR = 4. 7);
      and low family support (AOR = 3.4). Among Caucasians, health care providers'
      feeding preference (AOR = 6.1); having two or more breastfeeding role models (AOR
      = 4.1); not being enrolled in Women, Infants, and Children's Supplemental
      Nutrition Program (AOR = 3.0); having relied on infant-feeding advice (AOR =
      3.0); and prenatal alcohol use (AOR = 2.6) were associated with the decision to
      breastfeed. CONCLUSIONS: Prevalence and influences to breastfeed differ by
      patient race/ethnicity. We speculate that targeting the adolescent mother and
      members of her support system, educating them before and during pregnancy, and
      stressing benefits of this method while eliminating misinformation, especially
      among African-Americans, may be important intervention strategies to promote
      breastfeeding.

PMID- 9606255
TI  - Identification and Determination of Low-Molecular Weight Organic Compounds in
      Contaminated Fog Water Using Proton Nuclear Magnetic Resonance Spectroscopy

PMID- 9606254
TI  - Elementary school-based health center use.
AB  - BACKGROUND: The number of school-based health centers (SBHCs) has grown from 40
      in 1985 to >900 in 1996. During the 1996-1997 school year there were 914 SBHCs,
      32% of which were located in elementary schools. Despite the relatively large
      number of elementary SBHCs in existence, SBHCs serving elementary-aged students
      are not adequately represented in the literature. OBJECTIVE: To analyze physical
      and mental primary health care utilization in a comprehensive elementary SBHC for
      an underserved Hispanic population. DESIGN: Retrospective analyses of services
      used at an elementary SBHC during the 1995-1996 school year. We describe physical
      and mental health services utilization provided by SBHC staff who offered a range
      of primary medical and mental health services. PATIENTS: The study population was
      predominately Hispanic, and comprised of 811 elementary school students (grades
      preschool through fifth) registered for SBHC use. Analyses were conducted on 591
      students who used the SBHC. RESULTS: The 591 SBHC users made 2443 visits, ranging
      between 1 and 54 visits/individual; mean 4 visits/student. Two thirds of visits
      (1638) were medical provider visits, and 33% (798) were mental health provider
      visits. Most students (75%) saw a medical provider exclusively, 9% saw a mental
      health provider exclusively, and 16% of students were seen by both. Mean duration
      of medical provider visits +/-SD was 15 +/- 13 minutes, mean for mental health
      provider visits +/-SD, 37 +/- 16 minutes. Of the 3035 diagnoses, 64% were medical
      and 36% were mental health diagnoses. These diagnostic frequencies are grouped as
      follows: acute medical (31%), health maintenance (22%), depression (10%), non
      Diagnostic and Statistical Manual of Mental Disorders-IV mental health diagnoses
      (8%), conflict disorder/emotional disturbance (8%), chronic medical (8%),
      academic/learning disorder (7%), anxiety disorder (3%), and other (4%).
      CONCLUSIONS: High rates of SBHC utilization by this population and the range of
      diagnoses recorded suggest health care delivered in a comprehensive, culturally
      sensitive SBHC has the potential for impacting the health and well-being of
      underserved elementary-aged students.

PMID- 9606257
TI  - Pesticides and PCB contaminants in fish and tadpoles from the Kaweah River basin,
      California.

PMID- 9606258
TI  - Effects of pyrethroid insecticides on pest control operators.

PMID- 9606259
TI  - Effects of cooking on levels of PCBs in the fillets of winter flounder.

PMID- 9606260
TI  - DDT and its metabolites in human milk collected in Veracruz City and suburban
      areas (Mexico).

PMID- 9606261
TI  - Accelerated biodegradation of gamma-hexachlorocyclohexane (gamma-HCH) in a
      flooded alluvial soil retreated with gamma-HCH or its metabolite 1,2,4
      trichlorobenzene (TCB).

PMID- 9606262
TI  - Degradation behavior of malathion and fenitrothion residues on wheat and barley
      under different storage systems in Saudi Arabia.

PMID- 9606263
TI  - Biodegradation of chlorinated organic compounds by white-Rot fungi.

PMID- 9606264
TI  - Determination of zinc phosphide residues in corn (Zea mays) grain, fodder, and
      forage.

PMID- 9606265
TI  - Mercury concentrations in ambient air of the Rotorua, New Zealand, geothermal
      area.

PMID- 9606266
TI  - Metal levels in rain water from Kobe City in Japan.

PMID- 9606267
TI  - Guinea pig liver cytochrome P450 responsible for 3-hydroxylation of 2,5,2',5'
      tetrachlorobiphenyl.

PMID- 9606268
TI  - Inhibition and recovery kinetics of acetylcholinesterase activity in Drawida
      calebi and Octochaetona surensis, the tropical earthworms, exposed to carbaryl
      insecticide.

PMID- 9606269
TI  - Glutathione depletion by xenobiotics in Coturnix coturnix japonica.

PMID- 9606270
TI  - Effect of some pesticides on soil microorganisms.

PMID- 9606271
TI  - Evaluation of the acute toxicity to juvenile Pacific coho salmon and rainbow
      trout of some plant essential oils, a formulated product, and the carrier.

PMID- 9606272
TI  - Acute and chronic effects of gallium chloride (GaCl3) on tilapia (Oreochromis
      mossambicus) larvae.

PMID- 9606273
TI  - Effect of cadmium and zinc on respiration and photosynthesis in suspended and
      immobilized cultures of Chlorella vulgaris and Scenedesmus acutus.

PMID- 9606274
TI  - Accumulation of phenol by Potamogeton crispus from aqueous industrial waste.

PMID- 9606275
TI  - Bioaccumulation patterns of zinc, copper, lead, and cadmium in grey mullet, Mugil
      cephalus (L.), from harbour waters of Visakhapatnam, India.

PMID- 9606276
TI  - Intraoperative gastrin measurements during surgical management of patients with
      gastrinomas: experience with 20 cases.
AB  - Despite recent advances in imaging techniques for endocrine tumors of the
      duodenum and the pancreas, preoperative localization of gastrinomas is
      inconsistent. Successful surgical management of patients with Zollinger-Ellison
      syndrome (ZES) and removal of all gastrin-secreting tumors remains a difficult
      task. The aim of the study was to evaluate the predictive value of intraoperative
      gastrin measurements for successful surgical treatment in patients with
      gastrinomas. Intraoperative gastrin measurements were performed in 20 patients
      with ZES who underwent resection of gastrin-secreting tumors. Gastrin was
      measured with a radioimmunologic assay in blood samples obtained from a
      peripheral vein and from the portal vein at the beginning of the operation (T0)
      and 20 minutes after removal of the lesion(s) (T1). In 16 patients gastrin was
      also measured 4 minutes after injection of secretin 3 U/kg (T2). Thirteen
      patients (65%) were cured by surgery. In two of them, peripheral and portal
      gastrin levels were normal at T0, precluding any further interpretation of the
      test. Completeness of surgery was confirmed by normalization of gastrin levels at
      T1 or the absence of stimulation at T2 (or both) in 10 patients. In only one case
      did the gastrin levels remain elevated at T1 despite a favorable outcome after
      surgery. In each of the seven patients (35%) who had persisting disease at 1
      year, failure of the surgical procedure was predicted by persistence of high
      levels of gastrin at T1. In patients with hypergastrinemia, the positive
      predictive value of intraoperative gastrin measurement for completeness of
      surgery and the specificity were 100%. The negative predictive value was 88% and
      the sensitivity 91%. The overall accuracy of the test was 94%. In patients with
      ZES the normalization of systemic hypergastrinemia during surgery affirms the
      successful removal of all gastrin-secreting tumors. We conclude that
      intraoperative gastrin measurement is a valuable addendum for optimizing the
      surgical management of gastrinoma.

PMID- 9606277
TI  - Localization, malignant potential, and surgical management of gastrinomas.
AB  - Between 1987 and 1996 a total of 25 patients with proved Zollinger-Ellison
      syndrome (ZES) have been treated in our department. If preoperative imaging
      studies did not show diffuse metastatic disease, patients were scheduled for
      operation with a standardized surgical approach including thorough exploration
      and intraoperative ultrasonography (IOUS) of the pancreas and a longitudinal
      duodenotomy, with separate palpation of the anterior and posterior walls.
      Postoperatively, patients were followed up by physical examination, fasting
      gastrin levels, and the secretin stimulation test. Altogether 10 patients had
      duodenal wall gastrinoma, 14 patients pancreatic gastrinoma, and the tumor was
      not found in 1 patient. Only 15 tumors (60%) (2 duodenal wall and 13 pancreatic
      gastrinomas) could be visualized preoperatively. Intraoperatively, 24 of 25
      primary gastrinomas were localized. The mean size of duodenal wall gastrinomas
      (9.6 mm) was significantly smaller than that of pancreatic gastrinomas (28.7 mm)
      (p < 0.05). At the time of surgical exploration, five duodenal and seven
      pancreatic gastrinomas had metastasized. The incidence of lymph node metastases
      was similar for both tumor sites, whereas patients with pancreatic gastrinomas
      more frequently had liver metastases. The presence of liver metastases was the
      most important determinant for survival. Four patients (40%) with duodenal and
      seven with pancreatic (50%) gastrinomas (mean follow-up 5.2 years) were
      biochemically cured by operation. Of the remaining patients, eight are still
      alive with recurrent disease. Our results suggest that preoperative localization
      of gastrinomas often fails despite all modern imaging methods. Therefore a
      standardized surgical exploration of the pancreas including IOUS and a duodenal
      exploration should be performed to achieve optimal results. Preoperative
      diagnostic imaging tests should include computed tomography, ultrasonography, and
      somatostatin receptor scintigraphy to exclude diffuse metastases. In contrast to
      liver metastases, lymph node metastases do not have a significant influence on
      survival.

PMID- 9606278
TI  - Amitogenic alginates: key to first clinical application of microencapsulation
      technology.
AB  - Microencapsulation refers to a technique of immunoisolation by coating single
      cells or tissue with a semipermeable membrane. By combining microencapsulation
      with a specific tissue culturing method, iso-, allo-, and xenotransplantation of
      parathyroid tissue has been achieved without immunosuppression in a long-term
      animal model. Prior to its clinical use, continued analyses of the alginate, used
      as a coating substance, determined its mitogenic properties. Purification of the
      commercially available alginate was achieved using patented electrophoretic
      procedures, resulting in an amitogenic alginate suitable for use in humans.
      However, this alginate exhibited entirely different physical properties. We have
      recently shown that isotransplanted parathyroid tissue remains vital and
      functioning in vivo over long periods of time using the novel amitogenic
      alginate. It is essential to document, whether the alginate is able to maintain
      immunoisolation. We have therefore assessed its in vivo function compared to the
      mitogenic alginate in a transgenic animal model. Altogether 600 parathyroid
      glands from 300 Lewis rats (donor animals) were excised and subjected to tissue
      culture. Thereafter they were allotransplanted to 30 parathyroidectomized Dark
      Auita rats, microencapsulated with the amitogenic or the mitogenic alginate or
      naked, with 10 recipient animals in each group. Total serum calcium and
      parathyroid hormone levels were monitored continuously at weekly intervals for 30
      weeks. After 26 weeks the transplant beds were excised and subjected to
      histologic examination. More than 6 months after allotransplantation 9 of 10
      animals that had received amitogenic transplants, compared to 7 of 10 animals in
      the group with mitogenic microcapsules were normocalcemic. Animals that had
      received naked parathyroid tissue were hypocalcemic as soon as 2 weeks after
      allotransplantation. Correspondingly, normocalcemic animals showed vital
      parathyroid tissue inside the microcapsules, which were surrounded by a
      significantly smaller rim of fibroblasts when amitogenic alginate had been used.
      In addition to confirming physiologic long-term function, we were able to
      document for the first time that immunoisolation can also be achieved with the
      novel amitogenic alginate, which is suitable for clinical use.

PMID- 9606279
TI  - Reoperative surgery for organic hyperinsulinism: indications and operative
      strategy.
AB  - Organic hyperinsulinism has a good chance of cure by operation, although patients
      with diffuse or multiple disease run a high risk of recurrence or persistence of
      disease. Surgical management and outcome in these patients are presented and
      discussed. Between 1986 and April 1997 a total of 62 patients were operated on
      for organic hyperinsulinism [solitary 48, multiple 3, multiple endocrine
      neoplasia type I (MEN-I) 2, diffuse 4, malignant 5]. Persistence or recurrence
      occurred in 10 patients (16%). Among the six that persisted, four were malignant
      and two benign. All four of those that recurred were benign. Patients with benign
      disease presented with multiple tumors (n = 3), MEN-I syndrome (n = 1), and
      diffuse/nodular hyperplasia (n = 2). The duration between diagnosis and
      reintervention ranged from 1 to 10 years. Preoperative diagnosis was able to
      localize tumors in three patients (computed tomography 1, angiography 2, calcium
      stimulation 1). Operative procedures were multiple enucleations in two patients
      with sporadic disease, subtotal resection plus enucleation in the case of MEN-I
      syndrome, subtotal resection for diffuse hyperplasia, left resection for
      adenomatosis, and tumor extirpation after multiple previous operations. Long-term
      clinical and biochemical cure was achieved in five of six patients (mean follow
      up 5 years). Octreotide therapy shows good symptomatic control in the patient
      with operative failure. Reintervention for organic hyperinsulinism is successful
      (80% cure) and requires preoperative imaging and individual surgical management.

PMID- 9606280
TI  - Limited tumor involvement found at multiple endocrine neoplasia type I pancreatic
      exploration: can it be predicted by preoperative tumor localization?
AB  - Radiologically demonstrable pancreatic endocrine tumors are a frequent
      requirement for exploration in patients with multiple endocrine neoplasia type I
      (MEN-I). Such delayed intervention is accompanied by a 30% to 50% incidence of
      pancreatic endocrine metastases. This study explores biochemical tumor markers
      and operative findings in relation to preoperative pancreatic radiology in 25 MEN
      I patients. They underwent pancreatic surgery with (n = 19) or without (n = 6)
      radiologic signs of primary tumor and absence of metastases upon conventional
      examination, including OctreoScan testing (n = 10). Biochemical diagnosis
      required an increasing elevation of at least two independent pancreatic tumor
      markers. Tumor diameters averaged 1.1 cm (0-5 cm) and 0.9 cm (0.2-1.5 cm) in the
      patients with and without positive preoperative radiology, respectively. These
      investigations never displayed more than one of the consistently multiple tumors,
      and the results were falsely positive in 26%. Preoperatively unidentified
      regional or hepatic metastases were found at surgical exploration in 26% of
      patients with radiologic localization and in none of the others. Limited
      pancreatic tumor involvement necessitated intraoperative absence of metastases
      and pancreatic lesions </= 1 cm in diameter on palpation, intraoperative
      ultrasonography, and microscopy. It occurred in 37% and 50% of the patients with
      and without radiologic tumor localization, respectively. The number of positive
      tumor markers was similar for patients with limited and major disease (2.3 vs.
      2.7), whereas four or more such markers were found in all those with
      malignancies. The mean marker level was higher in patients with radiologically
      demonstrable tumors and lower in those with limited disease, but with a
      substantial overlap. OctreoScan testing was negative in all cases with limited
      disease and was the single most sensitive method (75%) in the others. Limited
      pancreatic disease could not be identified preoperatively, and the present means
      of biochemical pancreatic tumor identification invariably involved the presence
      of at least one lesion >/= 7 mm in diameter. Conventional pancreatic imaging is
      insensitive and nonspecific for recognizing even substantial pancreatic tumors
      associated with MEN-I.

PMID- 9606281
TI  - Somatostatin receptor subtypes, octreotide scintigraphy, and clinical response to
      octreotide treatment in patients with neuroendocrine tumors.
AB  - Several types of neuroendocrine tumor express high numbers of somatostatin
      receptors (sstr). We have compared the expression of sstr subtypes with the
      outcome of octreotide scintigraphy in patients with carcinoids and medullary
      thyroid carcinoma (MTC) in comparison with Hurthle cell tumors. The effect of
      sstr activation (octreotide treatment) on tumor markers was also studied in
      patients with disseminated carcinoid tumors. Six patients with carcinoid tumors
      (four midgut and two foregut), and three patients with thyroid tumors (one MTC,
      one Hurthle cell carcinoma, and one Hurthle cell adenoma) were studied.
      Octreotide scintigraphy visualized tumor sites in all nine patients. Macroscopic
      tumor was verified at these sites at subsequent surgical exploration. Using
      Northern blotting and subtype-specific riboprobes, sstr could be detected in all
      tumors examined. All five sstr subtypes were detected in most of the carcinoid
      tumors. All six carcinoids expressed sstr2. This was in contrast to the findings
      for the thyroid tumors analyzed, which also expressed several sstr subtypes but
      in some cases lacked expression of sstr2. This was also the case for normal
      thyroid tissue. Clinically, octreotide treatment of the patients with midgut
      carcinoid tumors resulted in palliation of hormonal symptoms accompanied by a
      significant reduction of urinary 5-HIAA levels (28-71%). These results indicate
      that carcinoid tumors frequently express all five sstr subtypes. The thyroid
      tumors also expressed multiple sstr but could lack expression of sstr2.
      Nevertheless, these tumors were visualized by octreotide scintigraphy, indicating
      that sstr2 expression is not a prerequisite for tumor imaging.

PMID- 9606282
TI  - Efficacy of single-voided urine metanephrine and normetanephrine assay for
      diagnosing pheochromocytoma.
AB  - Urinary catecholamines (CAs) and their metabolites are usually measured during
      the process of diagnosing pheochromocytoma (pheo), but a 24-hour urine collection
      is not convenient for outpatients. Since 1987 we have utilized "spot" urine
      metanephrine (MN) and normetanephrine (NMN) assays for management of patients
      with pheo or adrenal incidentaloma. MN and NMN were measured by radioimmunoassay
      in 82 patients with surgically proved pheo and 15 patients with incidentaloma. In
      10 patients with pheo, MN and NMN were measured with fractional every-3-hour
      urine samples, which were accumulated and then measured as a 24-hour urinary
      specimen. Fractions of 3-hour MN and NMN excretion were constant (MN 98.5 +/-
      9.6%, NMN 97.6 +/- 10.8%; 24-hour MN and NMN 100%). The average levels of MN and
      NMN in patients with pheo were 6801 ng/mg creatinine (Cr) (range 93-88,248,
      median 1426) and 5627 ng/mg Cr (range 219-31,528, mean 3190), whereas the MN and
      NMN levels in patients with incidentaloma were 123 ng/mg Cr (range 36-246, mean
      133) and 251 ng/mg Cr (range 84-472, mean 220), respectively. When we selected a
      cutoff value for MN + NMN of 1000 ng/mg Cr, the sensitivity was 97.6% and the
      specificity 100% for diagnosing pheo. When the standard was set as > 500 ng/mg Cr
      for either MN or NMN, both the sensitivity and specificity were 100%. The assay
      for MN and NMN is simple and effective, not only for screening but for diagnosing
      pheo and managing incidentaloma.

PMID- 9606283
TI  - Pheochromocytoma, a rare cause of hypertension: long-term follow-up of 55
      surgically treated patients.
AB  - Pheochromocytoma is a rare tumor that is found in only 0.1% of patients with
      diastolic hypertension. We analyze the results of our experience in management of
      pheochromocytomas and long-term results of its surgical treatment. From 1977 to
      1996 we operated on 55 patients with a pheochromocytoma: 29 males and 27 females
      with an average age of 41 years (range 10-63 years). In 44 (80.0%) patients
      episodic hypertension or paroxysms were observed; 7 (12.7%) patients had
      permanent hypertension, and 4 (7.3%) had a normal arterial blood pressure (ABP).
      131/123I-MIBG scintigraphy (33 patients) and magnetic resonance imaging (12
      patients) showed 100% sensitivity and computed tomography (47 patients) 97.9%
      sensitivity. At operation five (9.1%) tumors were bilateral, five extraadrenal,
      and five multiple. In four (7.3%) patients an association with familial syndromes
      (three MEN-IIb, one von Recklinghausen disease) was observed. Five (9.1%)
      malignant tumors were discovered, and two patients are still alive 30 and 104
      months after surgery, one of them with relapse. In 43 (78.2%) patients we
      preferred a flank incision, and no intraoperative deaths occurred. Mean follow-up
      was 88 months (6-232 months) with recurrence in only 1 (2.0%) of 50 patients
      without malignancy. In patients with benign pheochromocytomas the recurrence rate
      did not seem to be elevated in our series. Nevertheless, because the lifelong
      follow-up requires only annual 24-hour urinary catecholamine measurement (less
      than $40 per patient per year) and periodic ABP measurements, it is suggested for
      all patients who undergo surgery for pheochromocytoma.

PMID- 9606284
TI  - Evaluation of surgical treatment of renal hyperparathyroidism by measuring intact
      parathormone blood levels on first postoperative day.
AB  - Intact parathormone (inPTH) has a short half-life. Its blood level on the first
      day after total parathyroidectomy and subcutaneous parathyroid implantation (PTX
      + G) should therefore allow an early diagnosis of missed residual parathyroid
      tissue. We tested this hypothesis in 72 uremic patients who were followed for 6
      to 110 months after operation. Nine were reoperated for recurrence of the
      disease. Graft removal was successful in four patients who had post-PTX inPTH
      levels of 16 pg/ml or lower. In five patients, an overlooked parathyroid gland
      had to be resected. All of them had elevated post-PTX inPTH blood levels ranging
      from 72 to 791 pg/ml (upper normal limit 55 pg/ml). Three of these patients had
      presented with hypocalcemia after PTX. We conclude that the inPTH blood
      concentration on the first day after PTX allows more precise evaluation of the
      efficacy of the surgical procedure than the postoperative evolution of blood
      calcium levels. It is also useful for localizing the source of excessive PTH
      secretion (graft or overlooked gland) when the disease recurs.

PMID- 9606285
TI  - Vitamin D receptor gene polymorphism and parathyroid calcium sensor protein
      (CAS/gp330) expression in primary hyperparathyroidism.
AB  - Calcitriol, via its receptor (VDR), inhibits parathyroid hormone (PTH) secretion
      and cell proliferation. Physically linked polymorphic VDR alleles denoted b,a,
      and T, comprise a novel risk factor for postmenopausal primary
      hyperparathyroidism (pHPT) by their presumed coupling to reduced VDR expression.
      This study examines VDR gene polymorphisms, parathyroid calcium-regulated
      cytoplasmic calcium concentrations ([Ca2+]i) and parathyroid expression of a
      calcium sensor protein (CAS/gp330). Genomic DNA was obtained from 66
      postmenopausal women with pHPT and 66 age-matched female controls. Polymorphic
      VDR alleles were detected after polymerase chain reaction (PCR) and restriction
      digestion. Cryosections of pathologic parathyroid glands from 41 of the patients
      were immunostained with a monoclonal anti-CAS/gp330 antibody. Homozygosity for
      the VDR alleles b, a, and T was overrepresented in pHPT (p < 0.01-0.05) but did
      not couple to ED50 for calcium-regulated [Ca2+]i. The enlarged parathyroid glands
      possessed heterogeneous down-regulation of CAS/gp330. This down-regulation was
      the least conspicuous in the BBgenotype, and these few patients generally had
      larger parathyroid lesions (p < 0. 05). The VDR haplotype baTis a risk factor for
      pHPT possibly by hampering the regulatory actions of calcitriol. In contrast the
      BAt haplotype seems to be underrepresented in pHPT and to couple to larger
      parathyroid lesions as well as less deranged CAS/gp330 expression and parathyroid
      cell function. HPT in these individuals may relate to genetic events principally
      altering the regulation of cell proliferation, rather than calcium sensing of the
      parathyroid cells.

PMID- 9606286
TI  - Double parathyroid adenoma, a clinically nondistinct entity of primary
      hyperparathyroidism.
AB  - Double parathyroid adenoma (DA) has been suggested to be a clinically distinct
      entity of primary hyperparathyroidism (HPT). Altogether 659 patients with
      sporadic primary HPT were analyzed retrospectively by evaluating consecutive
      primary operations for more than three decades. Patients with postoperatively
      persistent HPT and those with incomplete medical, operative, or histologic
      records were disregarded. The mean age (+/- SD) at surgery was 60.9 +/- 12.7
      years; 78% of the patients were female; and the duration of postoperative follow
      up averaged 7.8 +/- 7.2 years. DA, defined as two enlarged parathyroid glands,
      was found in 77 patients (12%). Enlargement of a single gland (SA) or three or
      more glands (MA) occurred in 80% and 8%, respectively. DAs were bilateral in 72%
      of patients, and the weight of the two glands differed by 317 +/- 407 mg. The
      three histologic subgroups of patients exhibited no significant discrepancy with
      respect to age, classic symptoms of HPT, proportion of overtly asymptomatic
      individuals, or parathyroid tissue weight. A lower female predominance and extent
      of hypercalcemia and higher preoperative serum creatinine level occurred with DA
      and MA compared to SA. SA and DA differed from MA with respect to variably strong
      trends to lower postoperative incidences of recurrent HPT and hypoparathyroidism.
      DA seems to comprise an underrated histologic cause of HPT, which is eligible for
      a conservative operative approach. Clinical characteristics consistent with a
      distinct entity of sporadic primary HPT were not seen.

PMID- 9606287
TI  - Effect of subtotal thyroidectomy on natural history of ophthalmopathy in Graves'
      disease.
AB  - Graves' ophthalmopathy is a complex disease whose pathogenesis is thought to be
      autoimmune. The treatment of Graves' disease is considered to be related to the
      progression of Graves' ophthalmopathy. There have been no long-term prospective
      studies on the natural course of Graves' ophthalmopathy. In this study we
      assessed the influence of subtotal thyroidectomy on the outcome of Graves'
      ophthalmopathy, comparing it with that of radioactive iodine treatment.
      Altogether 287 untreated patients with Graves' disease referred to Ito hospital
      in 1989 were followed prospectively for 5 years. A group of 67 patients were
      treated with radioactive iodine, and 18 patients underwent surgery. Proptosis of
      the eyes was measured in all patients using Hertel's exophthalmometer. The mean
      value of proptosis in patients with untreated Graves' disease was 14. 8 +/- 0.2
      mm (mean +/- SEM), and after 5 years it increased slightly to 15.0 +/- 0.2 mm.
      The mean changes of proptosis in patients treated surgically and patients given
      radioactive iodine were -0.01 +/- 0.22 and 0.93 +/- 0.28 mm, respectively (p <
      0.05). In patients treated by subtotal thyroidectomy, ophthalmopathy did not
      change in 77.8%; it progressed in 5.6% and was alleviated in 16.7%. In patients
      treated with radioactive iodine, the ophthalmopathy did not change in 86.6%,
      progressed in 10.4%, and was alleviated in 3.0%. These findings indicate that
      surgery can be a better treatment than radioactive iodine for Graves' patients
      with ophthalmopathy.

PMID- 9606288
TI  - Hypocalcemia following thyroid surgery: incidence and prediction of outcome.
AB  - Postoperative hypocalcemia is a common and most often transient event after
      extensive thyroid surgery. It may reveal iatrogenic injury to the parathyroid
      glands and permanent hypoparathyroidism. We prospectively evaluated the incidence
      of hypocalcemia and permanent hypoparathyroidism following total or subtotal
      thyroidectomy in 1071 consecutive patients operated during 1990-1991. We then
      determined in a cross-sectional study which early clinical and biochemical
      characteristics of patients experiencing postoperative hypocalcemia correlated
      with the long-term outcome. Postoperative calcemia under 2 mmol/l was observed in
      58 patients (5. 4%). In 40 patients hypocalcemia was considered severe (confirmed
      for more than 2 days, symptomatic or both). At 1 year after surgery five patients
      (0.5%) had persistent hypocalcemia. We found that patients carried a high risk
      for permanent hypoparathyroidism if fewer than three parathyroid glands were
      preserved in situ during surgery or the early serum parathyroid hormone level was
      </= 12 pg/ml, the delayed serum calcium levels </= 8 mg/dl, or the delayed serum
      phosphorus level >/= 4 mg/dl under oral calcium therapy. When one or more of
      these criteria are present, long-term follow-up should be enforced to check for
      chronic hypocalcemia and to avoid its severe complications by appropriate
      supplement therapy.

PMID- 9606289
TI  - Anaplastic giant cell carcinoma of the thyroid gland: treatment and survival over
      a 25-year period.
AB  - Anaplastic giant cell carcinoma of the thyroid is a rare but highly malignant
      tumor. At the Karolinska Hospital in Stockholm, surgery, chemotherapy, and
      radiotherapy have been used separately or in various combinations in 81 patients
      admitted with this diagnosis during 1971-1997. In this study, we present the
      various multimodality treatment regimens and their changes over the years and the
      subsequent differences in survival and local tumor control. Overall, eight
      patients (10%) survived more than 2 years. All survivors were treated with
      combinations of chemotherapy, radiotherapy, and surgery. Among the patients who
      died, local tumor control was achieved by the therapy given in many cases. The
      results suggest that our current strategy with a combination of preoperative
      hyperfractionated accelerated radiotherapy, doxorubicin pre- and postoperatively,
      and debulking surgery whenever possible results in better local tumor control and
      an increased chance of survival.

PMID- 9606290
TI  - Clinicopathologic and immunohistochemical studies of papillary thyroid
      microcarcinoma presenting with cervical lymphadenopathy.
AB  - Although most papillary thyroid microcarcinomas (PMCs) are of little clinical
      significance, patients with PMCs occasionally have an unfavorable outcome,
      especially when they present with bulky nodal metastasis or distant metastasis.
      We have attempted to identify "high-risk" PMCs by evaluating clinical,
      pathologic, and immunohistochemical prognostic factors. Among 190 patients with a
      PMC, 156 without clinically apparent nodal metastasis had a benign course. The
      remaining 34 patients, who presented with cervical lymphadenopathy of at least 1
      cm, were studied. Three of the four patients who developed distant metastasis
      died of the disease, and the other died of local recurrence. All patients who
      developed distant metastasis or died of the disease had both nodal metastasis of
      at least 3 cm and a nonencapsulated type of primary lesion. All patients who
      developed distant metastasis showed both extracapsular extension of the
      metastatic lesions in lymph nodes and positive staining for transforming growth
      factor-beta3 (TGFbeta3) (a potent growth inhibitor) in the primary lesion. The Ki
      67 (an indicator of cell proliferation) labeling indices in the primary and
      metastatic nodal lesions of patients who died of cancer were significantly higher
      than those of the others with nonfatal disease. None of the patients showed P53
      (nuclear tumor-suppressor phosphoprotein) overexpression. In conclusion, patients
      with PMC who have both 3 cm or larger lymphadenopathy and a nonencapsulated type
      of primary lesion may be regarded as high-risk patients. Immunohistologic
      positivity for Ki-67 and TGFbeta3 in cancer cells is a potential indicator of
      aggressively malignant PMC.

PMID- 9606291
TI  - Thyroid cancer in patients with familial adenomatous polyposis.
AB  - The association between thyroid cancer and familial adenomatous polyposis (FAP),
      albeit rare, is well known. It has been suggested that the thyroid tumors have
      unique histologic characteristics and may be follicular in origin. Because of
      their rarity, treatment and long-term prognosis are uncertain. Twelve such
      patients (prevalence 399/100,000) seen during 1949-1995 were retrospectively
      reviewed. Histology was independently re-reviewed by two pathologists. There were
      11 female patients (two sisters) and 1 male patient, with a mean age of 28 years
      (range 15-61 years). Eight patients (66%) had multicentric tumors and five (42%)
      bilateral disease. Average tumor diameter was 1.8 cm (range 0.2-5.0 cm). Regional
      nodal metastases were present in two patients. All 12 thyroid cancers in this
      series were papillary. The one male patient demonstrated "typical" histology with
      variable papillary and follicular architecture, whereas the 11 female patients
      had tumors with unusual histology as described by Harach. Five patients (41%)
      were treated by total thyroidectomy, five with near-total thyroidectomy, and two
      with lobectomy alone. Mean follow-up was 142 months (range 7 months to 30 years).
      Regional recurrent disease occurred in two patients, one of whom died of the
      disease. The 5- and 20-year survivals were 90% and 77%, respectively. The results
      indicated that all tumors in this study were papillary, although atypical
      histology was encountered in 91%. The mean age (28 years) is younger than that of
      patients with sporadic disease. Multicentricity and bilateral disease are common.
      In view of this finding, total thyroidectomy should be strongly considered. Long
      term prognosis is excellent. The finding of unusual histology in a young patient
      with papillary thyroid carcinoma should arouse the suspicion of FAP.

PMID- 9606292
TI  - Prophylactic thyroidectomy in 75 children and adolescents with hereditary
      medullary thyroid carcinoma: German and Austrian experience.
AB  - When mutations of the RETproto-oncogene were found in 1993 to account for
      hereditary medullary thyroid carcinoma (MTC), surgeons obtained the opportunity
      to operate on patients prophylactically (i. e., at a clinically asymptomatic
      stage). Whether this approach is justified, and, if so, when and to which extent
      surgery should be performed remained to be clarified. A questionnaire was sent to
      all surgical departments in Germany and Austria. All of the patients who
      fulfilled the following criteria were enrolled: (1) preoperatively proved RET
      mutation; (2) age </= 20 years, (3) clinically asymptomatic thyroid C cell
      disease; and (4) TNM classification pT0-1/pNX/pN0-1/M0. Seventy-five patients
      were identified, and fifteen mutations were detected in six codons. Two
      adolescents had unilateral pheochromocytomas as part of the multiple endocrine
      neoplasia II (MEN-II) syndrome. No hyperparathyroidism was noted. All patients
      underwent total thyroidectomy, and 57 patients went on to have lymph node
      dissection. Parathyroid glands were removed in 34 patients and autografted in 11.
      Histopathology revealed MTC in 46 patients (61%, youngest 4 years); C cell
      hyperplasia (CCH) only was detected in the other 29 patients. Three patients had
      lymph node metastases (LNMs) the youngest being age 14 years. Calcitonin levels
      were not useful for differentiating between CCH and MTC, but in all patients with
      LNMs at least the stimulated calcitonin levels were assayed. After surgery, five
      patients (6.7%) sustained permanent hypoparathyroidism, and one patient (1.3%)
      had a permanent unilateral recurrent nerve palsy. All but three patients (96%)
      were biochemically cured. In conclusion, prophylactic total thyroidectomy can be
      performed safely in experienced centers. We recommend prophylactic total
      thyroidectomy at age 6. Cervicocentral lymph node dissection should be included
      when calcitonin levels are elevated or if patients are older than 10 years.
      Bilateral lymph node dissection should be performed if LNMs are suspected or when
      patients with elevated calcitonin are older than 15 years.

PMID- 9606294
TI  - American Diabetes Association 58th annual meeting and scientific sessions.
      Chicago, Illinois, USA. June 13-16, 1998. Abstracts.

PMID- 9606293
TI  - Latent subclinical medullary thyroid carcinoma: diagnosis and treatment.
AB  - Sporadic medullary thyroid carcinoma (SMTC) is usually diagnosed at a clinical
      stage often associated with lymph node involvement. Hence surgical treatment does
      not result in definitive cure in many patients. Studies have demonstrated that
      routine measurement of serum basal calcitonin (CT) in patients with nodular
      thyroid disease allows preoperative, early diagnosis of unsuspected SMTC. The aim
      of this work was to assess the results of surgery in patients operated on for
      subclinical SMTC detected preoperatively by measurement of serum CT. Results were
      compared with those obtained in patients with SMTCs diagnosed at a clinical stage
      and operated on during the same period. During a 4-year period (1993-1996) 24
      SMTCs were diagnosed and treated in our department. They were diagnosed at a
      clinical stage in 13 patients (group 1): palpable thyroid tumor (n = 11),
      palpable metastatic lymph node (n = 6), distant metastases (n = 4). In nine cases
      the diagnosis was made by both fine-needle aspiration cytology and serum CT
      measurement. In the four other cases the initial cytology was incorrect, but the
      diagnosis was revised on the basis of elevated basal CT values. In 11 patients
      (group 2) presenting with nodular thyroid disease, SMTC was not clinically
      detectable. SMTC was preoperatively suspected by elevated CT levels: basal CT >
      10 pg/ml and pentagastrin-stimulated CT peak > 100 pg/ml. One patient in group 1
      with distant metastases was not operated on. All of the other 12 patients
      underwent total thyroidectomy and extensive lymph node dissection. The mean size
      of the tumors was 27 mm. Lymph node involvement was found in nine patients. After
      surgery, CT levels returned to normal in five patients but remained elevated in
      five others; the two remaining patients died of distant metastases. All 11
      patients in group 2 underwent total thyroidectomy and central neck dissection.
      None of the 11 patients had nodal extension. All 11 patients are biochemically
      cured. It was concluded that routine measurement of basal serum CT in those with
      nodular thyroid disease allows early, preoperative diagnosis of subclinical SMTC
      and improves the results of surgery.

PMID- 9606295
TI  - 3rd European Congress of Epileptology. Warsaw, Poland, May 24-28, 1998.
      Abstracts.

PMID- 9606296
TI  - The 4th meeting of the Asian-Pacific Society for Neurochemistry and the annual
      meeting of the Korean Society for Neuroscience. Seoul, Korea, June 24-26, 1988.
      Abstracts.

PMID- 9606297
TI  - 45th Annual meeting of the Society of Nuclear Medicine. Toronto, Ontario, Canada.
      June 7-11, 1998. Abstracts.

PMID- 9606298
TI  - Adolescent guidelines: should we use them?

PMID- 9606300
TI  - ECG findings and hypertrophic cardiomyopathy.

PMID- 9606299
TI  - Thromboembolic events secondary to estrogen therapy.

PMID- 9606301
TI  - Gamma-hydroxy butyrate.

PMID- 9606302
TI  - Bacterial meningitis and antimicrobial therapy.

PMID- 9606303
TI  - Care of the premature infant: Part I. Monitoring growth and development.
AB  - When monitoring growth and development in the premature infant, physicians should
      make adjustments for the estimated due date. With minor exceptions,
      administration of immunizations is based on the chronologic age. Administration
      of hepatitis B vaccine should be delayed until the infant weighs 2,000 g (4 lb, 5
      oz). Administration of influenza vaccine should be considered in infants with
      chronic medical problems, and the pneumococcal vaccine may be beneficial at age
      two in children with chronic problems, especially pulmonary disease. Premature
      infants should also be monitored to assure appropriate nutrition. Breast-fed
      infants should probably receive vitamin supplements during the first year.
      Supplemental iron should be initiated at two weeks to two months after birth and
      continued for 12 to 15 months. Office care includes screening for problems that
      occur more frequently in premature infants, especially vision and hearing
      problems. Because many of these infants require care from multiple medical
      disciplines, coordination of care is another important role for the family
      physician. The goals of this care are to promote normal growth and development
      and minimize morbidity and mortality.

PMID- 9606304
TI  - Psychotherapy in primary care: the BATHE technique.
AB  - The family physician occupies a front-line position in the detection and
      treatment of emotional problems and psychiatric illnesses. The practice pattern
      of the family physician necessitates an efficient, effective model of
      psychotherapy The BATHE technique is a brief psychotherapeutic method that
      addresses the patient's background issues, affect and most troubling problem. The
      emphasis of the interview then shifts to how the patient is handling the problem
      and a demonstration of empathy by the physician. Some of the challenges in
      psychotherapy are presented, and cases in which the BATHE technique was used are
      described.

PMID- 9606305
TI  - Slipped capital femoral epiphysis.
AB  - Slipped capital femoral epiphysis occurs during the adolescent growth spurt and
      is most frequent in obese children. Up to 40 percent of cases are bilateral.
      Recent classification methods emphasize epiphyseal stability rather than symptom
      duration. Most cases of slipped capital femoral epiphyses are stable and have a
      good prognosis if diagnosed early. Unstable slipped capital femoral epiphysis has
      a much poorer prognosis because of the high risk of avascular necrosis. Early
      radiographic clues are the metaphyseal blanch sign and Klein's line. Once
      diagnosed, treatment should begin immediately. The most widely accepted treatment
      for a stable slipped capital femoral epiphysis is in situ fixation with a single
      central screw. The treatment for an unstable slipped capital femoral epiphysis is
      much more controversial. Corrective osteotomy is usually reserved for treatment
      of severe deformities after the patient has stopped growing.

PMID- 9606306
TI  - The women with dysuria.
AB  - Bacterial cystitis is the most common bacterial infection occurring in women.
      Thirty percent of women will experience at least one episode of cystitis during
      their lifetime. About one third of patients presenting with symptoms of cystitis
      have upper urinary tract infection. A careful history to identify risk factors
      for subclinical pyelonephritis is important. Symptoms of chronic cystitis
      accompanied by sterile urine without pyuria may represent interstitial cystitis.
      Dysuria may also be the principal complaint of women with vaginitis (infectious,
      atrophic or chemical) or urethritis. A stepwise diagnostic approach, accompanied
      by inexpensive office laboratory testing, is usually sufficient to determine the
      cause of dysuria.

PMID- 9606307
TI  - Stuttering: a brief review.
AB  - The etiology of stuttering is controversial. The prevailing theories point to
      measurable neurophysical dysfunctions that disrupt the precise timing required to
      produce speech. Stuttering is a common disorder that usually resolves by
      adulthood. Almost 80 percent of children who stutter recover fluency by the age
      of 16 years. Mild stuttering is self-limited, but more severe stuttering requires
      speech therapy which is the mainstay of treatment. Delayed auditory feedback and
      computer-assisted training are currently used to help slow down speech and
      control other speech mechanisms. Pharmacologic therapy is seldom used, although
      haloperidol has been somewhat effective.

PMID- 9606308
TI  - Implementing the guidelines for adolescent preventive services.
AB  - The Guidelines for Adolescent Preventive Services (GAPS) include recommendations
      developed and promoted by the American Medical Association's Department of
      Adolescent Health and are intended to organize, restructure and redefine health
      care delivery for 11- to 21-year-old patients. Data show that health risks in
      this age group are more social in origin than medical, and that these unhealthy
      behaviors can be recognized and interventions can be applied at an earlier age to
      reduce adolescent mortality and morbidity. In fact, evidence suggests that some
      interventions may result in a decrease in premature adult mortality. GAPS
      provides physicians with preventive service recommendations and a flow sheet that
      is useful for implementing and documenting these services during office visits.
      This system enables the busy physician to identify at-risk adolescent patients
      and provide them with information about changing unhealthy behaviors

PMID- 9606309
TI  - Management of dyslipidemia in adults.
AB  - The importance of treating dyslipidemias based on cardiovascular risk factors is
      highlighted by the National Cholesterol Education Program guidelines. The first
      step in evaluation is to exclude secondary causes of hyperlipidemia. Assessment
      of the patient's risk for coronary heart disease helps determine which treatment
      should be initiated and how often lipid analysis should be performed. For primary
      prevention of coronary heart disease, the treatment goal is to achieve a low
      density lipoprotein (LDL) cholesterol level of less than 160 mg per dL (4.15 mmol
      per L) in patients with only one risk factor. The target LDL level in patients
      with two or more risk factors is 130 mg per dL (3.35 mmol per L) or less. For
      patients with documented coronary heart disease, the LDL cholesterol level should
      be reduced to less than 100 mg per dL (2.60 mmol per L). A step II diet, in which
      the total fat content is less than 30 percent of total calories and saturated fat
      is 8 to 10 percent of total calories, may help reduce LDL cholesterol levels to
      the target range in some patients. A high-fiber diet is also therapeutic. The
      most commonly used options for pharmacologic treatment of dyslipidemia include
      bile acid-binding resins, HMG-CoA reductase inhibitors, nicotinic acid and fibric
      acid derivatives. Other possibilities in selected cases are estrogen replacement
      therapy, plasmapheresis and even surgery in severe, refractory cases.

PMID- 9606310
TI  - Prescription to over-the-counter drug reclassification.
AB  - Self-care is becoming increasingly popular among health care consumers. The
      availability of over-the-counter medications makes it possible for consumers to
      treat numerous ailments without the supervision of a health care professional.
      Many of the medications now available without a prescription were previously
      classified as prescription-only products. The U.S. Food and Drug Administration
      has procedures in place that allow prescription products to be reclassified as
      over-the-counter medications if certain criteria are met. Reclassified products
      have had clinical and economic effects on the U.S. health care system and have
      led to concerns among health care professionals. Patient education and counseling
      are particularly important to promote safe and effective use of over-the-counter
      products.

PMID- 9606311
TI  - "Toxic sock" syndrome.
AB  - For several months, a 17-year-old male athlete noticed that his feet had an
      itchy, burning sensation at the heels and toes. His foot odor had become so
      malodorous (somewhat akin to rotting fish) that he would not remove his shoes
      except immediately before washing his feet. Washing made the odor somewhat
      milder, but only for a short time. The patient had tried an over-the-counter
      "athlete's foot" powder without results. He had no other health problems and was
      not taking any medication. The accompanying figure shows the toes of his right
      foot.

PMID- 9606312
TI  - American College of Physicians issues guidelines on laboratory evaluation of Lyme
      disease.

PMID- 9606313
TI  - American Academy of Pediatrics releases report on cholesterol levels in children
      and adolescents.

PMID- 9606314
TI  - Small airways and asthma. An important therapeutic target?

PMID- 9606315
TI  - The development of large and small airways.

PMID- 9606316
TI  - The physiology of small airways.

PMID- 9606317
TI  - Assessment of airway inflammation in asthma.

PMID- 9606318
TI  - Small airway and alveolar tissue changes in nocturnal asthma.

PMID- 9606319
TI  - Inflammatory and structural changes in the small airways in bronchial asthma.

PMID- 9606320
TI  - Physiologic consequences of long-term inflammation.

PMID- 9606321
TI  - Drug delivery to the small airways.

PMID- 9606322
TI  - Effect of drugs on small airways.
AB  - Little is known about the effects of drugs on small airways. However, the small
      airways respond to constricting and dilating substances in vitro. Pathologic
      assessment demonstrates that small airways are inflamed, and the physiology
      suggests that they narrow and dilate. If after a period of treatment for asthma,
      all tests including the SBNT are normal, it would be safe to say that the small
      airways had been treated. However, we need to have some way of imaging the
      airways to decide whether or not there is abnormality in the small airways and to
      target the drugs that we are using to treat them. New ways of imaging, measuring,
      and performing a biopsy of the small airways are needed if we are going to make
      progress in this area.

PMID- 9606323
TI  - Cultured epithelial autografts in the treatment of extensive recalcitrant
      keloids.

PMID- 9606324
TI  - Subcutaneous emphysema. Air as a case of disease.

PMID- 9606325
TI  - Characteristic epiluminescent microscopic features of early malignant melanoma on
      glabrous skin. A videomicroscopic analysis.
AB  - OBJECTIVE: To investigate the characteristic epiluminescent microscopic features
      of early lesions of malignant melanoma affecting glabrous skin, which is the most
      prevalent site of the neoplasm in nonwhite populations. DESIGN: The
      epiluminescent microscopic features of various kinds of melanocytic lesions
      affecting glabrous skin were investigated using a videomicroscope. All the
      diagnoses were determined clinically and histopathologically using the standard
      criteria. SETTING: A dermatology clinic at a university hospital. PATIENTS: The
      following 130 melanocytic lesions consecutively diagnosed at our department were
      examined: 16 lesions of acral lentiginous melanoma, 6 lesions of malignant
      melanoma in situ, and 108 lesions of benign melanocytic nevus (acquired or
      congenital). MAIN OUTCOME MEASURE: The incidence of each characteristic
      epiluminescent feature was compared among disease categories. RESULTS: On
      epiluminescent microscopy, malignant melanoma in situ and the macular portions of
      invasive malignant melanoma showed accentuated pigmentation on the ridges of the
      skin markings, which are arranged in parallel patterns on glabrous skin. This
      "parallel ridge pattern" was found in 5 (83%) of 6 lesions of malignant melanoma
      in situ and in 15 (94%) of 16 lesions of malignant melanoma. The parallel ridge
      pattern was rarely found in the lesions of benign melanocytic nevus. Most benign
      melanocytic nevi showed 1 of the following 3 typical epiluminescent patterns: (1)
      a parallel furrow pattern exhibiting pigmentation on the parallel sulci of [he
      skin markings (54%), (2) a latticelike pattern (21%), and (3) a fibrillar pattern
      showing filamentous or meshlike pigmentation (15%). The remaining 11 benign nevi
      (10%) showed a nontypical pattern. CONCLUSION: Because epiluminescent microscopic
      features of early malignant melanoma on glabrous skin are characteristic, we can
      effectively detect early lesions using this noninvasive method.

PMID- 9606326
TI  - Use of chest radiography in the initial evaluation of patients with localized
      melanoma.
AB  - OBJECTIVE: To evaluate the use of an initial staging chest x-ray film in
      asymptomatic patients who present with localized primary cutaneous melanoma.
      DESIGN: The staging workup of 1032 consecutive asymptomatic patients with
      localized melanoma was retrospectively reviewed via database chart review.
      SETTING: Regional melanoma referral center in an academic medical center.
      PATIENTS: The melanoma database identified 1032 asymptomatic patients with
      localized melanoma for retrospective review. Of the patients studied, 876 (85%)
      of 1032 had an initial staging chest x-ray film performed. A chest x-ray film was
      considered initial if performed within 6 months of melanoma diagnosis. MAIN
      OUTCOME MEASURE: The rate of positive, negative, and suspicious findings of
      initial chest x-ray films. RESULTS: One hundred thirty (15%) of 876 patients had
      suspicious findings necessitating additional workup. Based on follow-up
      radiologic findings, only 1 (0.1%) of 876 had a true-positive chest x-ray film
      demonstrating pulmonary metastasis. CONCLUSIONS: The yield of detection of
      unsuspected pulmonary metastasis by chest x-ray film in the initial evaluation of
      asymptomatic patients with localized melanoma was exceedingly low (0.1%). Our
      results support the concept that routine chest radiograph screening in
      asymptomatic patients presenting with stage I and intermediate-thickness (1.5- to
      4.0-mm) stage II melanoma is unlikely to yield true-positive findings of silent
      pulmonary metastasis. No definitive conclusions were drawn for the subset of
      patients with stage II thick melanoma (> 4.0 mm) because of the small number of
      patients (n = 40) in our series. Prospective studies are necessary to ultimately
      define the yield of initial radiographs in asymptomatic patients with localized
      melanoma.

PMID- 9606327
TI  - Restrictive dermopathy. Report of 12 cases. Dutch Task Force on Genodermatology.
AB  - BACKGROUND: This study describes 12 cases of restrictive dermopathy seen during a
      period of 8 years by the Dutch Task Force on Genodermatology. We present these
      unique consecutive cases to provide more insight into the clinical picture and
      pathogenesis of the disease. OBSERVATIONS: Clinical features in more than 85% of
      these children were prematurity, fixed facial expression, micrognathia, mouth in
      O position, rigid and tense skin with erosions and denudations, and multiple
      joint contractures. Ten patients underwent histopathologic skin biopsy. The
      biopsy results showed flattening of rete ridges in all 10 patients, a thin dermis
      with collagen aligned parallel to the epidermis in 9 patients, and poorly
      developed dermal appendages in 9 patients. Additional findings in individual
      patients included blepharophimosis, inguinal skin tear, skin tear in the frontal
      neck area that developed during delivery, absent eyelashes, a wide ascendent
      aorta, and dextrocardia. Fibroblast cultures taken from 5 patients did not show
      abnormal alpha 2 beta 1 and alpha 1 beta 1 integrin expressions. CONCLUSIONS: The
      alleged rarity of restrictive dermopathy may be partially caused by medical
      unfamiliarity with this entity, despite its characteristic clinical and
      histopathologic picture. The pathogenesis of the disease still needs to be
      elucidated.

PMID- 9606328
TI  - Pilot ultrastructural evaluation of human preauricular skin before and after high
      energy pulsed carbon dioxide laser treatment.
AB  - BACKGROUND: Carbon dioxide laser resurfacing has recently come into favor for the
      treatment of photodamaged skin. While the clinical and histologic effects of high
      energy short-pulse carbon dioxide lasers on human skin have been investigated,
      the ultrastructural effects of these lasers have not been documented. Our
      objective was to study the ultrastructural effects of a high-energy pulsed carbon
      dioxide laser on photodamaged human skin. OBSERVATIONS: Before laser surgery, the
      ultrastructural changes characteristic of photodamaged skin were evident.
      Immediately after treatment, there was extensive coagulation necrosis of the
      epidermis and papillary dermis. Thirty days after treatment, there was no
      evidence of intercellular or intracellular edema, and ordered differentiation of
      the epidermal keratinocytes, with a loss of keratinocyte dysplasia, was seen.
      Increased numbers of desmosomes and tonofibrils were noted. New deposition of
      collagen was present in the papillary dermis. The ultrastructural findings seen
      at 90 days after treatment were similar to those seen at 30 days, apart from
      increased organization of collagen fibers in the papillary dermis. CONCLUSIONS:
      Treatment with the high-energy pulsed carbon dioxide laser appears to reverse the
      epidermal and dermal changes of photoaging on an ultrastructural level. These
      changes appear morphologically to be consistent with previously described
      clinical and histologic changes following laser resurfacing.

PMID- 9606329
TI  - Consensus workshop on the toxic effects of long-term PUVA therapy.
AB  - The possibility that there is an increased risk of melanoma in patients with
      psoriasis treated with psoralen-UV-A (PUVA) therapy has raised concern on the
      part of physicians and patients about the long-term safety of this treatment. In
      response to this concern, the National Psoriasis Foundation sponsored a workshop
      at which invited participants with expertise in PUVA therapy, psoriasis
      treatment, melanoma and nonmelanoma skin cancer, and epidemiological and clinical
      trials were asked to develop a consensus on the following 3 issues: the risk of
      long-term adverse effects of PUVA therapy with emphasis on nonmelanoma and
      melanoma skin cancer; the guidelines for physicians and patients for selection
      and use of PUVA therapy with consideration of the risk-benefit ratio of this
      treatment compared with the risk-benefit ratios of alternative treatments; and
      the directions for further evaluation of the long-term effects Of PUVA therapy.

PMID- 9606330
TI  - Cutaneous graft-versus-host disease.
AB  - Graft-versus-host disease (GvHD) includes inflammatory and/or fibrosing
      manifestations that may arise at various times after transplantation of any organ
      containing lymphoid cells. For the dermatologist, the importance of GvHD is real
      and current. Indeed, because it has become easier to perform bone marrow
      transplantation (EMT), the indications of BMT have become broader, making follow
      up of patients receiving grafts a widespread practice. Nonetheless, GvHD remains
      a frequent complication of BMT and its principal target organ is the skin.
      Furthermore, recent innovations, such as grafting of umbilical cord blood and the
      mobilization of peripheral blood progenitor cells, will be the source of new
      questions concerning the development of GvHD under these conditions. Finally,
      because of its analogies with other spontaneous idiopathic skin diseases, GvHD
      constitutes a model that may lead to a better understanding of the
      pathophysiological features of these diseases. In this review, the cutaneous
      aspects of GvHD are emphasized.

PMID- 9606331
TI  - Creeping eruption.

PMID- 9606332
TI  - Initial evaluation of melanoma. Don't stop getting that chest x-ray ... yet.

PMID- 9606333
TI  - Multiple blisters in a young boy. Linear IgA disease of childhood (LADC).
      (Chronic bullous dermatosis of childhood).

PMID- 9606334
TI  - Annular erythematous plaques and tibial pain in a child. Sweet syndrome.

PMID- 9606335
TI  - Solitary wrist plaque in an infant. Infantile myofibromatosis.

PMID- 9606336
TI  - Solitary congenital nodule in an infant. Solitary congenital self-healing
      reticulohistiocytosis (CSHR).

PMID- 9606337
TI  - Distinguishing the states of latency and reactivation is important for human
      herpesvirus 8.

PMID- 9606338
TI  - Family physicians discuss dermatologic training.

PMID- 9606339
TI  - Unilateral Darier disease with contralateral renal agenesis.

PMID- 9606340
TI  - On standard dermatologic definitions.

PMID- 9606341
TI  - On standard definitions of individual skin lesions.

PMID- 9606342
TI  - Standard definitions in dermatology: the need for further discussion.

PMID- 9606343
TI  - Cutaneous and visceral larva migrans due to Gnathostoma doloresi infection via an
      unusual route.

PMID- 9606344
TI  - Itraconazole as a new treatment for pustulosis palmaris et plantaris.

PMID- 9606345
TI  - Topical application of tazarotene in the treatment of nonerythrodermic lamellar
      ichthyosis.

PMID- 9606346
TI  - Multiple primary osteoma cutis.

PMID- 9606347
TI  - Skin biopsy gives the potential benefit in the diagnosis of systemic amyloidosis
      associated with cardiovascular involvement.

PMID- 9606348
TI  - Elevated circulating CA 15.3 levels in a subset of systemic sclerosis with severe
      lung involvement.

PMID- 9606349
TI  - Antihypertensive treatment in type II diabetes.

PMID- 9606350
TI  - Normal ECG or peaked T waves?

PMID- 9606351
TI  - Arthralgias following dilation and curettage.
AB  - A 36-year-old woman presented to the emergency department with right hip pain of
      one week's duration. An x-ray of the hip was unremarkable. She was diagnosed with
      trochanteric bursitis, given ibuprofen (800 mg tid) and crutches, and sent home.
      The next day, continual pain and progressive functional impairment prompted her
      to see an orthopedist. He concurred with the initial diagnosis and administered a
      corticosteroid injection into the right trochanteric bursa. Propoxyphene (65 mg
      q4h prn) was added to her medical regimen, and she was again sent home. Pain
      developed in the right sacroiliac area the next day. Within 24 hours, the right
      shoulder and right sternoclavicular joint were also involved, and the patient
      began having subjective fever and chilliness. She returned to the orthopedist and
      was immediately referred to a rheumatologist who ordered blood cultures and
      admitted her to the hospital.

PMID- 9606352
TI  - Dealing with drug-induced thrombocytopenia.
AB  - Unpredictable and potentially life-threatening, immune thrombocytopenia can occur
      with any drug, at times even after long, uneventful use. Heparin is the most
      common cause; although the fall in platelet count tends to be modest, these cases
      are particularly dangerous because of associated thrombosis. Much has been
      learned about heparin-induced disease, but complex issues remain.

PMID- 9606354
TI  - DHEA: science or wishful thinking?

PMID- 9606353
TI  - Urogynecology update: incontinence.
AB  - Physicians need to be more sensitive to urinary incontinence, because patients
      are unlikely to introduce the subject unless the symptoms are incapacitating.
      Failure to discuss the issue prevents patients from taking advantage of the many
      new drugs and mechanical devices that have become available. The vast majority of
      cases are treatable, often by relatively simple means.

PMID- 9606355
TI  - Minimizing your chances for documentation audits.

PMID- 9606356
TI  - Chest pain and dyspnea in a 17-year-old smoker.

PMID- 9606357
TI  - Acute coronary syndromes: 2. Antiplatelet agents.
AB  - Therapies with novel antiplatelet agents and anticoagulants are the focus of
      current research. When used separately or in combination, these agents prevent
      generation of thrombin by activated platelets. The new therapies, in conjunction
      with judicious use of fibrinolytic drugs and mechanical interventions, are
      revolutionizing the management of patients with acute coronary syndromes.

PMID- 9606358
TI  - Large granular lymphocytic leukemia: an overview.
AB  - Large granular lymphocytes are killer cells that differentiate into natural
      killer and T-cell types. Neoplastic proliferation of the lineages probably
      involves different etiologies, producing leukemias with distinct clinical
      presentations and prognoses. T-large granular lymphocytic leukemia has prominent
      autoimmune features and may occur in association with other autoimmune diseases,
      particularly rheumatoid arthritis.

PMID- 9606359
TI  - Medical therapies for inflammatory bowel disease.
AB  - Inflammatory bowel disease is a spectrum of disorders whose etiology and
      pathogenesis are unclear. No therapy is standard; many modalities exist for
      management. New drugs, improved formulations of existing drugs, combination
      therapy and biologic agents offer more effective relief and maintain disease
      remission.

PMID- 9606360
TI  - The promise of cancer genetics.

PMID- 9606361
TI  - Conventional cancer therapy: promise broken or promise delayed?

PMID- 9606362
TI  - The promise of molecular oncology.

PMID- 9606363
TI  - The promise of a good death.

PMID- 9606364
TI  - Locoregional treatments of unresectable liver metastases from colorectal cancer.

PMID- 9606365
TI  - Combined chemo-endocrine adjuvant therapy for patients with operable breast
      cancer: still a question?
AB  - Adjuvant systemic treatment delays relapse and prolongs survival in patients with
      operable breast cancer. However, the relative wealth of available agents and the
      heterogeneity of the target population contribute to considerable uncertainty
      about the optimal approach to particular patient groups. Systematic review and
      meta-analysis of the results of trials testing polychemotherapy have clearly
      established the value of such treatment. Endocrine treatment with tamoxifen was
      to be especially useful in patients with hormone-receptor positive tumours.
      Research in recent years has therefore concentrated on secondary questions, such
      as scheduling, dose intensity and new combinations of chemotherapeutic agents.
      Combined chemo-endocrine treatments, using polychemotherapy plus tamoxifen,
      ovarian ablation or both, have been compared with either modality alone. Other
      endocrine agents such as fluoxymesterone acetate, medroxyprogesterone acetate
      and, recently, LH-RH analogues have also received attention. The systematic
      review presented here suggests that combined cytotoxic and endocrine therapies
      might be the most effective use of available treatments for most, if not all,
      patients, and highlights the unresolved questions requiring further research.

PMID- 9606366
TI  - Chemotherapy in squamous cell carcinoma of the cervix uteri: present role and
      perspectives.

PMID- 9606367
TI  - A review of the pharmacology and clinical activity of new chemotherapeutic agents
      in lung cancer.

PMID- 9606368
TI  - Immunotherapy and breast cancer.

PMID- 9606369
TI  - Dyspnoea in patients with advanced cancer: incidence, causes and treatments.

PMID- 9606370
TI  - 43rd Annual meeting of the Health Physics Society. Minneapolis, Minnesota, USA.
      12-16 July 1998. Abstracts.

PMID- 9606371
TI  - Ionic versus nonionic contrast media: a prospective study of the effect of rapid
      bolus injection on nausea and anaphylactoid reactions.
AB  - PURPOSE: The purpose of our study was to evaluate the effect of bolus infusion of
      contrast medium (ionic versus nonionic) on the incidence of nausea and
      anaphylactoid reactions. METHOD: We prospectively studied 1,827 patients who had
      bolus enhanced body CT scans and divided them into four groups: 725 patients
      received higher osmolality contrast medium (HOCM) at the slower bolus rate of 1
      2.5 ml/s (SLOW-HOCM group); 650 patients were in the FAST-HOCM group and received
      the same ionic contrast medium at 4-5 ml/s; 250 patients received lower
      osmolality contrast medium (LOCM) at 1-2.5 ml/s, forming the SLOW-LOCM group; and
      202 patients in the FAST-LOCM group got the same nonionic agent at 4-5 ml/s.
      RESULTS: We found no significant difference in the rate of nausea among the first
      three groups: SLOW-HOCM (3.9%), FAST-HOCM (4.9%), and SLOW-LOCM (3.2%). A
      statistically significant lower incidence of nausea (0.5%) was found in the FAST
      LOCM group. Anaphylactoid reactions were significantly more common in both groups
      who received HOCM (8.3 and 9.1%) compared with the groups who received LOCM (2.0
      and 2.5%). CONCLUSION: The bolus injection of warmed ionic contrast medium at a
      rate of 1-2.5 ml/s causes no significant increase in nausea compared with similar
      infusion rates of nonionic agents. For CT protocols that require infusion rates
      of 4-5 ml/s, the use of a nonionic agent is associated with a significantly
      reduced prevalence of nausea. The prevalence of anaphylactoid reactions is not
      affected by the rate of injection.

PMID- 9606372
TI  - MR compatibility of Med EL cochlear implants: clinical testing at 1.0 T.
AB  - PURPOSE: Our aim was to evaluate the MR compatibility of Med EL cochlear implants
      by performing in vitro and in vivo tests. METHOD: All experiments were done on a
      1.0 T machine. Potential movement of the cochlear electrode relative to a scale
      was recorded. Potential dislodgment of the magnetic receiver coil was evaluated
      with the coil fixed to the retroauricular skin of a volunteer. Temperature
      changes were measured with temperature sensors fixed to the electrode, performing
      standard MR sequences. In 11 patients, MRI of the brain was performed 1 day
      before explantation of the devices using standard MR sequences. Testing of the
      auditory abilities was done before and after the examination. All explanted
      devices were assessed for function. RESULTS: There was no detectable movement of
      the electrode or the receiver coil nor any temperature change. There were no
      adverse events for the patients. All 11 explanted cochlear implants retained
      their function. CONCLUSION: Med EL cochlear implants are not a firm
      contraindication for MRI.

PMID- 9606373
TI  - CT of neural plexus invasion in common bile duct carcinoma.
AB  - PURPOSE: Our purpose was to analyze the CT findings of neural plexus invasion in
      common bile duct carcinoma. METHOD: We studied 16 patients with common bile duct
      carcinoma who underwent surgery. Of these, neural invasion was seen in 10
      patients. CT findings were retrospectively reviewed and correlated with the
      surgical and pathological findings. RESULTS: Irregular masses adjacent to the
      medial aspect of the uncinate process were observed in 4 of 14 patients with
      distal common bile duct carcinoma. These lesions extended medially and showed
      contiguity with the superior mesenteric artery and/or celiac axis, corresponding
      to neural plexus invasion with desmoplastic change. Increased attenuation of the
      fat between the common bile duct and the proper hepatic artery was seen in two of
      two patients with proximal common bile duct carcinoma, associated with neural
      plexus invasion in the hepatoduodenal ligament. CONCLUSION: The location and
      spread of neural plexus invasion in common bile duct carcinoma are characteristic
      and can be diagnosed by CT.

PMID- 9606374
TI  - MRI of fistula-in-ano: a comparison of endoanal coil with external phased array
      coil techniques.
AB  - PURPOSE: The objective of our study was to compare MRI of fistulas-in-ano using
      an endoanal coil with that using a pelvic phased array coil and to assess the
      value of a combined approach by correlating the findings with those at surgery.
      METHOD: Twenty consecutive patients with clinical suspicion of perianal sepsis
      were studied using an endoanal coil immediately followed by a phased array coil.
      T1 weighted and STIR images in transverse and coronal planes were made with each
      coil and analysed by noting the presence and site of a collection and primary
      track, the position of any internal opening, and subcutaneous or supralevator
      extension. Operative findings were similarly recorded. RESULTS: Of 20 patients
      with suspected fistulas, 8 had simple fistulas, 8 had complex fistulas, and 4 had
      no current evidence of infection. The concordance between MR and surgery for
      identifying the presence and site of the collection, the primary track, and the
      internal opening in both simple and complex cases was superior using the endoanal
      coil as compared with the phased array. Both coils together reflected the
      findings of the endoanal coil used alone. However, for supralevator/subcutaneous
      extension, concordance was superior using the phased array compared with the
      endoanal coil, and a combined approach reflected the values of the phased array
      coil used alone. CONCLUSION: Endoanal MRI is highly sensitive in the delineation
      of fistulas-in-ano. In combination with phased array techniques, it provides
      valuable preoperative assessment in both simple and complex cases.

PMID- 9606375
TI  - Breath-hold T2-weighted MRI of hepatic tumors: value of echo planar imaging with
      diffusion-sensitizing gradient.
AB  - PURPOSE: The purpose of our study was to evaluate the efficacy of echo planar
      imaging (EPI) as a breath-holding T2-weighted technique for imaging focal hepatic
      lesions. METHOD: Forty-eight patients with focal hepatic lesions (9 metastases,
      21 hepatocellular carcinomas, 1 cholangiocarcinoma, 16 hemangiomas, and 2 cysts)
      underwent single shot EPI with and without a small diffusion-sensitizing gradient
      (DSG) (beta values = 55 s/mm2) at 1.5 T. Comparison was made with breath-holding
      T2-weighted fast SE (FSE) sequences. RESULTS: Lesion-to-liver signal intensity
      ratio of EPI was significantly better than that of T2-weighted FSE (p < 0.05) in
      patients with metastasis. Use of DSG suppressed bright signals from vessels or
      periportal tissue, resulting in better conspicuity of small lesions. EPI with DSG
      visualized more metastatic deposits than T2-weighted FSE (p < 0.01). CONCLUSION:
      EPI with a small DSG is helpful for detection of small hepatic metastases.

PMID- 9606376
TI  - Von Meyenburg complexes of the liver: imaging findings.
AB  - PURPOSE: Our purpose was to present imaging findings of six cases proven or
      supposed to be von Meyenburg complexes (VMCs) with a basis of reviewing the
      pathologic literature and to describe imaging points for the diagnosis of typical
      VMC along with its differential diagnosis. METHOD: Six cases were diagnosed as
      VMC of the liver with imaging modalities (one had histopathologic proof). Both
      ultrasound (US) and CT were available for all cases, and MRI was used for three
      cases. Follow-up with US, CT and/or MRI was performed in five cases. RESULTS: US
      detected varying abnormalities of the livers in four cases. CT and MRI revealed
      multiple or numerous intrahepatic tiny (usually < 5 mm) cystoid lesions in all of
      the cases. The lesions were scattered throughout the livers, and some of them
      were located more frequently adjacent to the medium-sized portal veins than to
      the hepatic veins of similar size on CT. Moreover, some lesions were apparently
      located in the subcapsular areas (up to the hepatic capsules). They were usually
      irregular in shape and showed no enhancement but increased in number by
      approximately 80-150% after administration of intravenous contrast medium. The T2
      weighted MR images and MR cholangiopancreatography showed the lesions to be much
      more apparent and to be more numerous than T1-weighted images did. Follow-up of
      five cases with imaging modalities did not show remarkable change of the lesions.
      CONCLUSION: Despite our limited experience, VMC lesions seem to show some CT and
      MR features different from those of other multiple small hepatic lesions. They
      presented as multiple or numerous intrahepatic tiny cystoid lesions usually with
      irregular contour, scattered throughout the liver up to the subcapsular areas,
      and were detected in far greater number by enhanced CT or T2-weighted MR images
      than by unenhanced CT or T1-weighted images. They showed no remarkable change on
      long term follow-up imaging. We propose that a diagnosis of typical VMC could be
      made after analyzing CT or MR images carefully with good understanding of its
      pathologic basis, but imaging follow-up is necessary in oncology patients.

PMID- 9606377
TI  - Dynamic MR follow-up of small hepatocellular carcinoma after percutaneous ethanol
      injection therapy.
AB  - For patients with small hepatocellular carcinomas (HCCs) treated by percutaneous
      ethanol injection (PEI) therapy, dynamic MRI has been performed to evaluate the
      therapeutic efficacy at our institute. In this pictorial essay, we illustrate the
      various dynamic MR findings of HCCs after PEI therapy, including complete
      necrosis, partial necrosis, local recurrence, and pathologic conditions such as
      arterioportal shunt and contractive changes of hepatic parenchyma. We also
      present the limitation of dynamic MRI in the evaluation of therapeutic
      effectiveness of PEI therapy.

PMID- 9606378
TI  - Compression of large uterine myoma by sacral promontory: MR findings.
AB  - We present the MR findings of three cases of large uterine myomas that had
      geographically nonenhancing areas that were compressed by the sacral promontory.
      These nonenhancing areas on contrast-enhanced T1-weighted images showed no
      abnormal signal intensity on T2-weighted images. On delayed images following
      contrast medium administration, the nonenhancing area eventually enhanced
      homogeneously. There was no evidence of degeneration at pathologic examination.
      We think that the sacral promontory may compress large myomas with vascular
      insufficiency, resulting in delayed contrast enhancement of that area.

PMID- 9606379
TI  - Improved technique for pancreatic MRI: value of oblique fat suppression imaging
      with oral barium administration.
AB  - PURPOSE: Our goal was to determine the efficacy of a dedicated protocol for
      pancreatic MRI using fat suppression, oblique plane orientation, and barium as an
      oral contrast agent. METHOD: Fifty-two patients were enrolled in our study. In
      each patient, the stomach and duodenum were opacified with 300 ml oral barium. In
      all patients conventional SE T1- and T2-weighted images and fat-suppressed axial
      and oblique T1-weighted images of the upper abdomen and the pancreas,
      respectively, were obtained. The different T1-weighted sequences were compared
      for visualization of the pancreas and for lesion conspicuity. Oblique images were
      obtained in a plane parallel to the overall axis of the pancreas. All sequences
      were qualitatively assessed by two independent blinded readers and statistically
      compared. RESULTS: The combination of fat suppression and oblique imaging
      significantly improved the visualization of the different anatomic portions of
      the normal pancreas as well as pathologic findings in the pancreas in 70-92% of
      the cases compared with conventional axial T1-weighted imaging (p < 0.001) and in
      52-75% of the cases compared with axial fat-suppressed T1-weighted imaging (p <
      0.001), respectively. Increased image noise and blurring artifacts resulted in
      slight image degradation after Gd-DTPA administration. Barium as a duodenal
      contrast agent was beneficial for delineation of the pancreatic head from the
      adjacent bowel structures. CONCLUSION: In pancreatic imaging, fat-suppressed T1
      weighted imaging is superior to conventional T1-weighted imaging, and oblique
      imaging is superior to axial imaging. Intravenous Gd-DTPA administration was
      useful only in selected cases.

PMID- 9606380
TI  - Dynamic helical CT of breast tumors.
AB  - PURPOSE: The purpose of our study was to test dynamic helical CT (hCT) in the
      evaluation of breast tumors. METHOD: Thirty-six patients with 39 suspected
      lesions underwent breast hCT before and 1, 3, and 8 min after intravenous
      contrast medium administration. A marked enhancement (> or = 100%) at 1 or 3 min
      without increase at 8 minutes was considered as the primary indicator for
      malignancy. Twenty carcinomas, one metastatic non-Hodgkin lymphoma, six
      fibroadenomas, and six other benign findings were histologically assessed. Six
      cases had negative fine needle aspiration cytology and at least a 2 year negative
      follow-up. RESULTS: hCT showed a 100% sensitivity and 83.3% specificity.
      Considering carcinomas and fibroadenomas, significant differences were found for
      the percent enhancement at 1 min (p = 0.002) as well as for the density increase
      or decrease at 3 versus 1 min (p = 0.0035), at 8 versus 1 min (p = 0.0027), and
      at 8 versus 3 min (p = 0.0180). CONCLUSION: hCT proved to have a high diagnostic
      efficacy in evaluating breast tumors. Even though it involves some exposure to
      radiation, it should be considered in patients in whom MR is contraindicated.

PMID- 9606381
TI  - Assessment of local recurrence after breast-conserving therapy with MRI.
AB  - PURPOSE: The purpose of our study was to evaluate the relevance of MR mammography
      in the diagnosis of early and late tumor recurrence after breast-conserving
      therapy. METHOD: Sixty-seven patients receiving breast-conserving therapy
      underwent 84 MR mammographies in a period between 1 month and 14 years after end
      of therapy. Dynamic measurements were made following application of contrast
      agent. The course of signal intensity changes was evaluated in focal lesions and
      irradiated and contralateral glandular tissue. RESULTS: All 10 malignant lesions
      (7 local recurrences, 1 chest wall recurrence, 2 contralateral carcinomas) showed
      a > 75% increase in signal intensity within th first minute after contrast agent
      application. In all patients examined during the first year after end of therapy
      (n = 29), increased enhancement in irradiated parenchyma was observed compared
      with the contralateral breast, but only in two patients the increase was > 75%
      within the first minute. CONCLUSION: Already in the first year after end of
      therapy, MRI can improve diagnostic accuracy in the assessment of breast cancer
      recurrence. More than 12 months following end of therapy, MR mammography can
      demonstrate tumor recurrence with a sensitivity of nearly 100% and a specificity
      rising to > 90% in differentiating tumor from therapy-induced changes.

PMID- 9606382
TI  - Spiral CT appearance of resolving clots at 6 week follow-up after acute pulmonary
      embolism.
AB  - PURPOSE: The purpose of this work is to describe the spiral CT appearance of
      resolving clots at 6 week follow-up in patients with acute pulmonary embolism
      (PE). METHOD: Nineteen patients with acute PE initially identified with spiral CT
      scan underwent repeat CT examinations at 6 week follow-up after the start of
      anticoagulant therapy. The appearances of the clots on the initial CT scan and
      follow-up CT scan were analyzed. RESULTS: Normalization of the pulmonary arteries
      at follow-up was seen in six patients (32%) only. Residual abnormalities were
      present in 13 of 19 patients (68%). Resolving clots were seen as eccentric wall
      adherent filling defects (22%) or filling defects with central contrast material
      (3%). CONCLUSION: Resolving clots after acute PE can be seen with follow-up CT
      scan in the majority of patients. It is important to be familiar with these
      findings.

PMID- 9606383
TI  - The optimization of helical thoracic CT.
AB  - PURPOSE: Our purpose was to determine the optimal helical thoracic CT scanning
      protocol. METHOD: Three adult Suffolk sheep under general anesthesia were
      repeatedly scanned by a variety of variable thickness helical and conventional
      plus thin section high resolution (lung gold standard) CT sequences,
      reconstructed for mediastinal (standard interpolator and algorithm) and lung
      parenchymal (extrasharp interpolator, bone algorithm) detail. The images were
      evaluated in a random order by five separate blinded, experienced imagers
      utilizing a predetermined grading scale. RESULTS: At equivalent slice
      thicknesses, the mediastinal images showed no statistically significant
      differences between conventional and helical CT using pitches of 1.0, 1.5, and
      2.0. However, the 5-mm-thick sections, regardless of technique, performed better
      than did either the 2- or the 10-mm-thick section images. For the lung
      interstitium, there was an obvious and marked advantage to reconstructing the
      lung images separately from the mediastinal images with edge-enhancing algorithms
      and interpolators. With 1-mm-high mA thin section, high resolution lung CT as the
      gold standard, 2 mm conventional and helical pitch 1.0, 1.5, and 2.0 images were
      all graded equivalent. Of the 5 mm images, the helical pitches of 1.0 and 1.5
      were graded equivalent to the gold standard. All of the 10 mm lung sections using
      both conventional and helical CT were graded statistically worse than the gold
      standard (p < 0.05). CONCLUSION: The use of helical CT with a 5 mm beam
      collimation and a pitch of 1.0 or 1.5 reconstructed twice to maximize both the
      mediastinal and the lung parenchymal detail provides the optimal way to routinely
      evaluate the chest.

PMID- 9606384
TI  - Cavitary lung cancer producing granulocyte colony-stimulating factor: a mimicker
      of lung abscess.

PMID- 9606385
TI  - Intravascular lymphomatosis of the lung: radiologic findings.

PMID- 9606386
TI  - Development of vertebral fractures in patients with multiple myeloma: does MRI
      enable recognition of vertebrae that will collapse?
AB  - PURPOSE: We assessed the relationship between the presence and size of focal
      marrow abnormalities detected with MRI in vertebral bodies and the subsequent
      occurrence of vertebral fractures at follow-up in patients with multiple myeloma
      (MM). METHOD: We reviewed 179 follow-up MR examinations of the thoracic and
      lumbar spine prospectively obtained in 37 patients with Stage 3 MM. For each of
      131 vertebral bodies that fractured during follow-up, the status of the vertebral
      bone marrow was assessed on the last MR study obtained at a mean time interval of
      4 months prior to fracture occurrence. When focal lesions were observed before
      fracture in vertebral bodies that later collapsed, their size was compared with
      that of the contemporary lesions observed in vertebrae that did not collapse.
      RESULTS: Of 131 fractures, 82 (63%) appeared in vertebrae previously free of
      focal bone marrow abnormality at MRI and 49 (37%) appeared in vertebrae in which
      focal lesions were present on the previous MR study. The size of the lesions that
      preceded fractures (median 15 mm; range 6-50 mm) was not statistically different
      from the size of the contemporary lesions (median 15 mm; range 5-60 mm) that did
      not lead to fracture (p > 0.30). CONCLUSION: This study in patients with MM
      suggests a lack of correlation between the preexistence of focal vertebral marrow
      lesions detected with MRI and the subsequent development of vertebral fractures.

PMID- 9606387
TI  - Osteomyelitis of the pelvis/hips in paralyzed patients: accuracy and clinical
      utility of MRI.
AB  - PURPOSE: The goal of our study was to determine the accuracy and clinical utility
      of MRI in the diagnosis of osteomyelitis of the pelvis/hips in paralyzed
      patients. METHOD: In 44 paralyzed patients, 59 consecutive MR examinations of the
      pelvis/hips were evaluated prospectively. Criteria for diagnosis of osteomyelitis
      were based on those established in previous studies of complex, nonhematogenous
      osteomyelitis (diabetic foot). Average follow-up was 3 years. The standard of
      reference for the diagnosis of osteomyelitis was histologic/microbiologic results
      of surgical biopsy specimens or clinical follow-up. Note was made if decubitus
      ulcers, sinus tract, fistula, fluid collection, abscess, septic arthritis, joint
      effusion, bursitis, or heterotopic ossification was present on MRI. Comparison of
      the extent of infection by MRI and surgical margins was performed. Effect on
      surgical treatment was defined by absence of recurrent infection at the surgical
      site within 6 weeks of limited resection. RESULTS: The criteria for diagnosis of
      osteomyelitis were fulfilled in 49 of 57 MR studies for an overall accuracy of
      97%. There was one false-negative MR study. MRI for the diagnosis of
      osteomyelitis yielded a sensitivity of 98% and a specificity of 89%. There were
      41 decubitus ulcers, 28 sinus tracts, 2 fistulae, 14 fluid collections, 15
      abscesses, 9 hips with septic arthritis, 10 "bland" hip effusions, 5 cases of
      trochanteric bursitis, and 30 patients with heterotopic ossification. Twenty-one
      patients underwent limited surgical resection guided by MR findings in which only
      the enhancing area was resected. There was only one recurrence of osteomyelitis
      at the surgical margins. CONCLUSION: MRI is accurate in the diagnosis of
      osteomyelitis and associated soft tissue abnormalities in spinal cord-injured
      patients. MRI can delineate the extent of infection in guiding limited surgical
      resection and preserving viable tissue.

PMID- 9606388
TI  - Preoperative description of severe acetabular defects caused by failed total hip
      replacement.
AB  - PURPOSE: The reconstruction of severe acetabular defects, caused by failed hip
      prostheses, is difficult and complex. Current radiographic descriptions of the
      defects are inadequate. We sought to more accurately describe remaining bone and
      improve surgical planning using 3D physical models based on CT data. METHOD:
      Nineteen patients (20 hips) with failed total hip replacements and severe
      acetabular defects were selected. Plain radiography and CT were performed. Solid
      3D physical models of each pelvis were constructed using the CT data. Bone loss
      in structurally important regions was measured from radiographs, models, and
      intraoperative observation. Comparisons were made of the radiograph-based and
      model-based bone loss measurements, surgical plans, and interobserver
      variability. RESULTS: There was no statistical difference between the model-based
      measurements and the intraoperative measurements. Radiographs statistically
      underestimated bone loss by at least 20% (p < 0.01). Interobserver bone loss
      grading was poor for the radiograph-based measurements (kappa = 0.06) but was
      substantial for the model-based measurements (kappa = 0.73). In only half the
      cases was prosthesis type correctly selected based on radiographs. Model-based
      planning selected the correct prosthesis type in all cases. CONCLUSION: The
      physical models were substantially more accurate than radiographs for measuring
      acetabular defects and for surgical planning.

PMID- 9606389
TI  - Edge complexity and partial volume effects.
AB  - PURPOSE: The accuracy of MR brain image segmentation is limited by so-called
      partial volume effects. We hypothesized that "edge complexity" (i.e., tissue
      class interface border complexity) significantly influences the magnitude of such
      effects. METHOD: To investigate partial volume effects and provide a vehicle for
      validation of segmentation algorithm accuracy in brain MRI. We developed a
      computer simulation, the "gigabrain." The simulation is based on interpolated
      (supersampled) data from actual MR studies. The voxels are assigned to one of
      five compartments (gray matter, white matter, CSF, fat, or "background"), the
      compartment interfaces are "jittered" to add high frequency "signal" or "edge
      complexity," and the voxels are populated with appropriate values determined from
      human data, low pass filtered (based on the MR scanner's point spread function),
      and subsampled back to the sampling and voxel size of the original MR data set.
      RESULTS: In comparison studies with actual phantoms and human MR data, our
      simulation approach was able to produce images whose appearance and quantitative
      values were comparable with the actual data, but only when edge complexity was
      added to the original MR data. CONCLUSION: Edge complexity is a significant
      source of partial volume effects. MR simulations must include edge complexity to
      adequately test segmentation algorithms.

PMID- 9606390
TI  - Accuracy of object depiction and opacity transfer function optimization in CT
      volume-rendered images.
AB  - Volume rendering is a visualization technique that has important applications in
      diagnostic radiology and radiotherapy. A methodology is presented for (a)
      evaluation of the quantitative accuracy of representation of known objects in
      volume-rendered scenes and for (b) optimization of the opacity transfer function
      to achieve the most accurate representation of a particular structure. Results
      using this methodology are shown for structures representing each of the major
      tissue interfaces and are discussed.

PMID- 9606391
TI  - Reliability and validity of an algorithm for fuzzy tissue segmentation of MRI.
AB  - PURPOSE: A new multistep, volumetric-based tissue segmentation algorithm that
      results in fuzzy (or probabilistic) voxel description is described. This
      algorithm is designed to accurately segment gray matter, white matter, and CSF
      and can be applied to both single channel high resolution and multispectral
      (multiecho) MR images. METHOD: The reliability and validity of this method are
      evaluated by assessing (a) the stability of the algorithm across time, rater, and
      pulse sequence; (b) the accuracy of the method when applied to both real and
      synthetic image datasets; and (c) differences in specific tissue volumes between
      individuals with a specific genetic condition (fragile X syndrome) and normal
      control subjects. RESULTS: The algorithm was found to have high reliability,
      accuracy, and validity. The finding of increased caudate gray matter volume
      associated with the fragile X syndrome is replicated in this sample. CONCLUSION:
      Since this segmentation approach incorporates "fuzzy" or probabilistic methods,
      it has the potential to more accurately address partial volume effects,
      anatomical variation within "pure" tissue compartments, and more subtle changes
      in tissue volumes as a result of disease and treatment. The method is a component
      of software that is available in the public domain and has been implemented on an
      inexpensive personal computer thus offering an attractive and promising method
      for determining the status and progression of both normal development and
      pathology of the CNS.

PMID- 9606392
TI  - Acoustic echoplanar scanner noise and pure tone hearing thresholds: the effects
      of sequence repetition times and acoustic noise rates.
AB  - PURPOSE: Our goal was to determine the effects of acoustic echoplanar scanner
      noise on pure tone hearing thresholds in normal volunteers and to determine the
      influence of echoplanar sequence repetition time on threshold effects. METHOD:
      With use of a calibrated audiometer, pure tones ranging from 125 to 8,000 Hz were
      delivered monaurally to 10 normal-hearing volunteers in a quiet MR scanner suite
      and in the presence of acoustic scanner noise produced by three separate single
      shot blipped echoplanar pulse sequences varying only in repetition time (TR =
      1,000, 2,000, or 3,000 ms), with all other parameters including the number of
      slices held constant. The magnitude of noise-induced threshold changes and the
      slopes of the threshold curves produced by each of the three echoplanar pulse
      sequences were then analyzed using multiple comparisons and a least significant
      difference method. The shapes of the threshold curves produced in each background
      state were best fit using a quadratic effect for frequency in a mixed effects
      linear model and compared using F test statistics. RESULTS: All of the volunteers
      demonstrated entirely normal hearing thresholds throughout the full range of
      tonal frequencies tested (< 25 dB) when no acoustic scanner noise was present in
      the scanner suite. Pure tone hearing thresholds significantly increased (p <
      0.01) in the presence of acoustic scanner noise, with the magnitude of change
      inversely proportional to the repetition time and therefore the rate of periodic
      noise production by the echoplanar sequence used. The shape of the threshold
      curve in the presence of noise produced by the 1,000 ms TR sequence was not
      equivalent across the frequency spectrum tested but had a quadratic distribution
      with peak effects at 750-2,000 Hz. As the repetition time was increased and the
      periodic noise rate decreased, the magnitude of the noise-induced threshold
      changes significantly lessened (p < 0.01) and the quadratic distributions of the
      threshold curves changed significantly (p < 0.01), tending toward a more planar
      configuration. CONCLUSION: Background acoustic echoplanar scanner noise can
      significantly increase pure tone thresholds in the optimal frequency hearing
      range (125-8,000 Hz). However, the threshold effects are not equivalent across
      the frequency spectrum, and the magnitude of threshold changes is dependent on
      the rate at which periodic acoustic scanner noises are produced for a given
      sequence repetition time.

PMID- 9606393
TI  - Visualization of the cervical spinal cord with FDG and high-resolution PET.
AB  - PURPOSE: Our aim was to evaluate the visibility of the cervical spinal cord with
      [18F]2-fluoro-2-deoxyglucose (FDG) and a high-resolution PET scanner and to
      quantify the glucose utilization by the cervical cord. METHOD: Twenty-one normal
      subjects and three cervical myelopathy patients were studied. The visibility of
      the cervical spinal cord in sagittal and coronal sections was evaluated. The
      metabolic rate of glucose (MRGlu) and standardized uptake value (SUV) of FDG in
      the cord were calculated. RESULTS: The entire cervical spinal cord was clearly
      visualized in 57% of the subjects: the upper cord in 81%, the middle cord in 73%,
      and the lower cord in 57%. The MRGlu of the normal cord was 1.93 +/- 0.37 mg/100
      g/min. SUV was constant across all the vertebral levels and negatively correlated
      with subject age. In the myelopathy patients, the SUV of the entire cervical cord
      was lower than in the age-matched normal subjects. CONCLUSION: These preliminary
      results indicate that the cervical spinal cord can be visualized as a normal
      structure in routine head and neck PET imaging and that FDG-PET may provide
      quantitative information about spinal cord disorders.

PMID- 9606394
TI  - MRI of mucosal malignant melanoma of the head and neck.
AB  - PURPOSE: The objective of this study was to determine the characteristic MR
      findings for mucosal malignant melanomas of the head and neck. METHOD: We
      retrospectively analyzed the MR images for six patients with this entity. T1
      weighted SE images with and without gadolinium and T2-weighted fast SE images
      were obtained. MR images were analyzed qualitatively and quantitatively by
      comparing the signal intensity of the melanoma with that of muscle. RESULTS: On
      T1-weighted images, five melanomas were hyperintense and one was isointense. On
      T2-weighted images, five were of mixed intensity and one showed isointensity. The
      mean signal intensity ratio of the primary melanoma to muscle was 1.51 and 1.39
      on T1-weighted images with and without gadolinium, respectively. These values
      were not statistically significant. CONCLUSION: Hyperintensity on T1-weighted
      images is characteristic of this entity, but not universal.

PMID- 9606395
TI  - Dental MR tomography of the mandible.
AB  - Imaging of the jaw bones is routinely achieved by conventional X-ray tomography
      or CT. In this study a new imaging procedure (dental MR tomography) is
      introduced. Five subjects were positioned in the standard neck coil of a 1.0 T MR
      scanner, and T1- and T2-weighted imaging of the mandible was performed in the
      axial plane. After the examination, the data were reconstructed as panorama and
      cross-sectional images using a software package for dental imaging on a
      workstation. The neurovascular bundle within the mandibular canal (MC), its
      relation to the teeth, and the pulp chambers of the teeth were demonstrated
      excellently in all cases. Edema and reactive hypervascularization due to an
      inflammatory process were also well visible. Dental MR tomography could become a
      good alternative to X-ray-based imaging modalities of the jaw bones by
      additionally offering the advantage of directly imaging the neurovascular bundle
      within the MC. Furthermore, administration of contrast agent for differentiation
      of pathological alterations is possible.

PMID- 9606396
TI  - Marchiafava-Bignami disease: reversibility of neuroimaging abnormality.
AB  - Marchiafava-Bignami disease (MBD) was diagnosed in a malnourished 43-year-old
      patient with chronic alcoholism, severe generalized extrapyramidal rigid
      syndrome, and severe dyspraxia. Cranial CT and MRI demonstrated isolated lesions
      in the geno and splenium of the corpus callosum (CC) characteristic for MBD. On
      thiamine therapy, a slow but steady recovery of clinical symptoms occurred, and
      serial CT and MRI studies demonstrated marked reversibility of abnormalities in
      the CC. Besides clinical improvement with a good functional outcome, reversal of
      CT and MRI abnormalities may occur in MBD.

PMID- 9606397
TI  - Transient neurotoxicity associated with FK506: MR findings.
AB  - We report a patient presenting with transient neurotoxicity who developed edema
      in the cerebral and cerebellar cortex following bone marrow transplant and
      administration of FK506, a widely used immunosuppresive agent.

PMID- 9606398
TI  - Aunt Minnie's corner. High-riding jugular bulb.

PMID- 9606399
TI  - [Effects of stress at different times after irradiation on capacity of humoral
      immune response in mice].
AB  - It was shown, that sensitivity of immune response to stress in postirradiated
      period essentially depends from the dose of irradiation (1, 2 Gy) and the period
      after irradiation. The sensitivity was not distinguished from intact mice in
      early period further the sensitivity of immune response can be increased (1 Gy)
      or can be decreased (2 Gy), stress can be stimulated of the antibody-formation to
      sheep red blood cells in late period after irradiation.

PMID- 9606400
TI  - [Natural excretions of mice in the postradiation period and contact induction of
      immunodeficiencies].
AB  - It was showed that the daily transfer of natural secrets litter from irradiated
      mice to intact mice decreased parameters of intact mice immune reactivity in 14
      days. Presumedly this effect, conditioned of pathological odours, discovered on
      one from mechanism of contact induction second immunodeficient, also caged intact
      with irradiated animals.

PMID- 9606401
TI  - [Several parameters of the state of the nervous, immune and endocrine systems in
      newborn rats exposed to irradiation during the preimplantation period of
      embryogenesis].
AB  - Protracted prenatal irradiation of animals at the preimplantation stage of
      embryogenesis is shown to produce disturbances in the development of regulation
      systems, with their consequences persisting up to sexually mature period of
      postnatal life. Unknown before, these effects of preimplantation irradiation give
      the experimental confirmation to the main statement of the previously proposed
      theoretical concept of the "systemic teratogenesis": the ultimate effect of
      prenatal irradiation is a distortion of the structure of postnatal
      neuroimmunoendocrine regulation in the direction of overdevelopment of its
      endocrine component with the following coadaptive underdevelopment of the nervous
      and immune components.

PMID- 9606402
TI  - [Kinetics of metabolism and mechanisms of formation of absorbed doses in the
      mouse testis from incorporated Cs-137].
AB  - The process of accumulation of absorbed doses from incorporated 137Cs in the body
      and gonads of male mice was investigated in our experiments. The radionuclide
      accumulated in gonads has very long time of excretion, and as result the
      radionuclide can be treated as long lasting and permanent source of alpha- and
      beta-radiation in gonads. The rates of total exposed doses in gonads were in 2.0
      3.0 times higher then the average total exposed dose in hole body.

PMID- 9606403
TI  - [Evaluation of relative biological effectiveness of tritium oxide based on
      biochemical indices of blood in rats].
AB  - The influence of tritium oxide injected peritoneally of the range of activity of
      5.5 MBq/g to 111 MBq/g versus gamma-radiation of 137Cs with decreasing dose rate
      in biochemical parameters of blood in rats was compared. It was shown that
      relative biological effectiveness of tritium oxide was higher than that for
      metabolism and it was equal to 1.5 in average.

PMID- 9606404
TI  - [Study of the effect of a food additive Medetopect on metabolic kinetics of
      transuranic radionuclides in animal body].
AB  - The effect of Medetopect, a food additive, on the metabolic kinetics of
      transuranics (239Pu and 241Am) has been studied experimentally in white mongrel
      rats following chronic intake by ingestion. The Medetopect application has been
      shown to be advantageous for reduction of the 239Pu and 241Am absorption from and
      content of the gastrointestinal tract of the animals.

PMID- 9606406
TI  - [Radioprotective effect of hydroxy phenylethanolamine phenolic hydroxyl esters].
AB  - Experiments are carried out on 3000 mice, irradiated in dose 8 Gy (LD97/30). A
      number of phenolic hydroxyl esters of phenylephrine, norphenylephrine and
      epinephrine has the high RPE (70-100%) within 1 h before irradiation. 3-esters of
      3-hydroxy phenylethanolamines are active in small doses (19-50 mumol/kg) and
      protect per os too. RPE of 3-benzoylphenylephrine realizes via alpha 1
      adrenoreceptors.

PMID- 9606405
TI  - [Radioprotective effectiveness of indralin in local gamma irradiation of the
      skin].
AB  - In experiment with mice radioprotective properties of indralin were investigated
      on local application of the substance at the site of the hind to be exposed to
      gamma-60Co-rays in the doses of 16.7-39.0 Gy at rate of the dose -1.5-1.6 Gy/min.
      After s.c. injection (50, 100, 200 and 300 mg/kg) radioprotective efficiency of
      indralin in term of DRF was 1.35, 1.50, 1.35 and 1.05 for early radiation damages
      of the skin, -1.13, 1.62, 1.53 and 1.45 for late radiation contracture of the
      leg, -1.10, 1.50, 1.20 and 1.16 for radiation amputation of the foot. Under 3
      fold every 2 days fractionated irradiation in total dose of 42.9 Gy
      radioprotective efficiency of indralin in term of DRF made 1.62 for early
      radiation damages of skin, -1.52 for radiation oedema of the foot, > 1.5 for
      radiation contracture of leg. After external cutaneous application of indralin
      solution on 70% DMSO solvent radioprotective efficiency of the drug in term of
      DRF was 1.28 and 1.37 for early and late radiation damages of skin while DRF of
      DMSO being equal to 1.14 and 1.22 responsively.

PMID- 9606407
TI  - [Therapeutic antiradiation properties of leukinferon].
AB  - In experiments with three species of animals (mice, rabbits, monkeys) irradiated
      with sublethal and lethal doses of gamma-irradiation, it was observed, that
      leukinferon used in 4 hours or 10 days after provided antiradiation therapeutical
      effect. When lethal dose was used (mice) the survival of animals was
      significantly increased. The preparation decreased depression of the functional
      activity of leukocytes as it was observed with IFH-alpha and gamma-production.
      Pestoring this function was accelerated. Phenomena pancytopenia and
      thrombocytopenia induced by radiation were decreased. Therapeutical effect was
      explained with capacity of the preparation to defence the hemopoietic organs from
      the radiation and to stimulate hematopoiesis. So, spleen weights and quantity of
      cells into bone marrow were higher in experimental group in comparison with
      control at any observation. CFUs were also higher (with optimal dose of
      preparation). Stimulation of the restoring processes was confirmed also by more
      intensive increasing of the reticulocyte quantities in the circulation of
      experimental monkeys within 20 days. Then their level became more close in both
      groups. The preparation stimulated also differentiation of immune effectors:
      immature neutrophils were absent in the circulation of experimental monkeys.
      Production of IFN-gamma (which is function of T-lymphocytes) was restored more
      fast. As a result, immunoreactivity of monkeys in experimental group was more
      complete and restored faster: the growth of the automicroflora on the skin
      surface became to increase 7 days later and was restrained. Leukinferon hindered
      the development of acute radiation sickness symptoms.

PMID- 9606408
TI  - [EPR-spectroscopy of human blood preparations. Remote sequelae of the Chernobyl
      accident].
AB  - It was shown, that as a result of Chernobyl accident the intensity of the EPR
      signal of hemoproteins and ferroporphyrins of people blood increased, that most
      probably connected with disturbing of ferroprotein metabolism. Maximum intensity
      values had people, irradiated with low doses (to 2 cGy), that corroborate the
      theory of danger these doses for the people organism.

PMID- 9606409
TI  - [Assessment of chronic radiation exposure as one of risk factors of the
      development of cancer in industrial city residents exposed to radioactive
      pollution].
AB  - With the help of mathematical methods of pattern recognition the analysis of
      complex cancer risk factors was conducted aiming at estimation the role of
      chronic radiation exposure in development of lung and breast cancer in dwellers
      of an industrial city exposed to irregular radioactive contamination as a result
      of an accident at PO "Mayak". It was shown, that chronic radiation exposure is an
      important factor, influenced the development of malignant neoplasms in city
      population.

PMID- 9606410
TI  - [Cs-137 air pollution of vegetation in the territory of Bryansk region].
AB  - Based on daily measurements of 137Cs concentrations in the surface air due to
      resuspension from the Chernobyl contaminated soil surface, air contamination of
      natural grass with the radionuclide has been determined for Novozybkov and
      Bryansk in 1992-1993. The map of air contamination with 137Cs in the Bryansk
      region has been calculated.

PMID- 9606411
TI  - [Methods of calculation of radionuclide transfer as a result of fires in the
      Chernobyl zone].
AB  - In spring 1994 by fires in 30-km zone of ChNPP it was fixed the increasing of
      radioactive products of burning concentration in the air and densities of its
      losses at the track of a smoke train in comparison with usual conditions. The
      model of the atmospheric transfer of radioactive aerosols and smoke particles is
      offered. It is shown that fires in this zone result in increasing of internal
      exposure doze.

PMID- 9606412
TI  - [Radioprotective effect of weak ultra-low frequency alternating magnetic field in
      adrenalectomized mice].

PMID- 9606413
TI  - [Modification of radiosensitivity of mice by combination of alternating magnetic
      field and fractionated irradiation with small daily doses over many days].
AB  - Everyday before radiation combination of weak magnetic field and fractioned
      radioactive irradiation in dose of 0.5 Gy up to total doses of 6.0-8.0 Gy
      increased surviving of mice by 34-53%, prolonged the life-time 1.5 times as much
      (half as much). It also decreased the rate of accumulation of damaged systems,
      extended average time of death and the value of dose changing factor, and reduced
      the gradient of damaged systems.

PMID- 9606414
TI  - [Nonspecific reaction of the nervous system to non-ionizing radiation].
AB  - Using different electromagnetic fields we investigated reactions of brain by
      different methods (psychophysical, behavioural, electrographical and
      morphological). We discover nonspecific initial adaptive reaction of brain
      (IARB). This IARB include weak pain, inhibition of learning, EEG reaction of
      synchronisation and activation neuroglia.

PMID- 9606416
TI  - Production of WTC.ZI-zi rat congenic strain and its pathological and genetic
      analyses.
AB  - A new rat congenic strain, WTC.ZI-zi, was produced after eleven generations of
      backcrossing between ZI strain as a donor strain and WTC strain as an inbred
      partner. WTC.ZI-zi/zi homozygous rats generally exhibit more conspicuous body
      tremor and much earlier occurrence of flaccid paresis than the original ZI
      strain. The average life span of the congenic strain is approximately nine
      months, which is also much shorter than that of the original ZI strain.
      Pathological analysis of the central nervous system of the congenic strain
      revealed more aggravated vacuolation and hypomyelination than in the original ZI
      strain. Establishment of the genetic profile with microsatellite markers showed
      that the congenic strain was genetically almost identical to the WTC strain
      except for a small chromosome segment bearing the zitter gene. Analysis of
      markers in this region implied that the length of the donor segment was
      approximately 13.4 centimorgans which corresponded to 0.65% of the total genome.
      Thus, these results suggested that expressional alterations of zitter gene were
      due to replacement of the genetic background from the original ZI strain to the
      WTC strain. Furthermore, the WTC.ZI-zi congenic strain could provide a refined
      tool for the analysis of zitter mutation, because the congenic strain has a
      strict control strain, WTC, and the length of the donor chromosome is genetically
      defined.

PMID- 9606415
TI  - [Reply to the letter-to-the-editors by V.A. Pitkevich, V.K. Ivanov, S.Iu. Chekin,
      A.F. Tsyb, "Concerning the problem of radiation exposure levels to the Chernobyl
      AES accident clean-up participants, included in Russian Medical-Dosimetric State
      Registry"].
AB  - Theoretical and practical problems related to the dosimetric data verification
      for recovery workers at the Chernobyl NPP are considered. The distinctions in
      definitions epsilon-entropy in paper [1] and delta-entropy in [2] are considered.
      In a certain measure this distinctions explain distinction in conclusions, made
      in these papers. Method of dosimetric data collection, used by Institute of
      Biophysics and its difference from the method of data acquisition, used in
      national Medical-dosimetric registers is described. Results on determination of a
      share of participants given for various clean-up worker divisions, contained in
      pointed delta-shape peaks, received by two various methods, stated in [2] and
      [6], are compared and their satisfactory conformity with one another is
      established.

PMID- 9606417
TI  - Extension of conserved regions in the rat and mouse genomes by chromosomal
      assignments of 29 rat genes.
AB  - We recently constructed a comparative genetic map of the rat, mouse and human
      genomes based on information obtained from several databases. In this study, we
      performed chromosomal assignments of 29 rat genes with somatic cell hybrid
      clones, in order to clarify and extend the conserved regions in the rat and mouse
      genomes. As a result, the conserved regions were extended by 89 cM. Together with
      our previous report, the length of the conserved regions in the rat and mouse
      spans 847 cM on the mouse linkage map, indicating that 53% of the mouse genome is
      covered by homologous regions in the rat. In addition, four conserved regions
      were newly revealed. The method described in this study appears to be simple and
      efficient for constructing a whole genome comparative map of the rat and mouse.

PMID- 9606418
TI  - Ontogenetic changes in responsiveness to benzodiazepine receptor ligands on
      ultrasonic vocalizations in rat pups.
AB  - The ontogenetic changes in responsiveness to benzodiazepine receptor ligands on
      ultrasonic vocalizations in rat pups from the age of day 3 to day 12 were
      evaluated. Rat pups, while separated from their dam and littermates and placed in
      a cold environment, emit ultrasonic vocalizations. These ultrasonic calls became
      attenuated dose-dependently in number and power after administration of the
      anxiolytic diazepam (0.25-1.0 mg/kg, s.c.), but the inhibitory effect of diazepam
      at the highest dose was less on day 6 and day 9. Moreover, type 1 benzodiazepine
      receptor ligands, Ro16-6028 and Ro23-0364 (0.5-2.0 mg/kg, s.c.), also dose
      dependently attenuated the ultrasonic vocalizations 30-60 min after injection.
      The inhibitory effects of these drugs became more pronounced with the increasing
      age of the pup, and they were equivalent on day 12 to those in adult rats. These
      results suggest that different ontogenetic changes in development of two subtypes
      of central benzodiazepine receptors of pups might be related in the
      psychopharmacological mediation of the ultrasonic vocalization.

PMID- 9606419
TI  - Prenatal and postnatal maternal effects on body weight in cross-fostering
      experiment on two subspecies of mice.
AB  - A cross-fostering experiment was conducted on two quite distinct subspecies of
      mice, domesticated laboratory mouse of CF#1 (Mus musculus domesticus) and
      Yonakuni wild mouse (Yk, Mus musculus molossinus yonakuni), to estimate the
      prenatal and postnatal maternal effects on body weight of offspring. Mating was
      done between subspecies, two or three females being mated to a male at nine-ten
      weeks of age. Two dams of different subspecies that littered at the same day were
      used as a group of foster dams. Litters were standardized to six young mice in
      order that a dam nursed three mice of her own litter and three mice from that of
      another subspecies dam. The litters were weaned at 3 weeks of age. The body
      weight of individual mice was determined at 1, 3, 6 and 10 weeks of age. The
      result demonstrated that prenatal maternal effects were more important than
      postnatal maternal effects in contributing to the variation in body weight at all
      ages examined. Prenatal maternal effects accounted for 61-96% and 35-92% of total
      variance in males and females, respectively; whereas postnatal effects accounted
      for 1-7% for males and 3-23% for females. Analysis for between postnatal within
      prenatal, and between prenatal within postnatal indicated that expression of the
      body weight of offspring was limited by the genetic type of their prenatal dam
      and influenced by the postnatal environment of nursing dam. The greatest body
      weight was attained by offspring born to prenatal CF#1 dams and nursed by
      postnatal CF#1 dams, followed by CF#1 offspring born to CF#1 dams and nursed by
      Yk dams, Yk offspring born to Yk dams and nursed by CF#1 dams and the lightest
      ones were Yk offspring born to Yk dams and nursed by Yk dams.

PMID- 9606420
TI  - Open eyelids at birth, a new mutation in the musk shrew, Suncus murinus.
AB  - The mutation designated "open eyelids at birth" arose spontaneously in the BAN
      strain of the musk shrew (Suncus murinus). This is the first report on this kind
      of mutation in the shrew. Mating experiments suggested that the mutant character
      is controlled by an autosomal recessive gene with about 43% penetrance. The
      symbol oeb(open eyelids at birth) was proposed for the mutant gene. Affected
      shrews were fully viable and fertile. Phenotypically, the affected shrews were
      characterized by one or both eyelids open at birth. By 9 days of age, the exposed
      and dried eyeballs usually dropped off and became missing or sometimes looked
      microphthalmic. Except for the eye abnormality, the affected shrews showed no
      obvious external abnormalities. Light-microscopically, the affected shrews with
      missing eyes or microphthalmia-like eyes did not have complete eye structures,
      and only remnants of some eye tissue were observed. In the phenotypically normal
      oeb/oeb shrews with closed eyelids at birth, no histological eye abnormalities
      were noted. Thus, the mutant character observed may simply be caused by a failure
      of the eyelids to close.

PMID- 9606421
TI  - Effect of mouse intestinal bacteria on incidence of colorectal tumors induced by
      1,2-dimethylhydrazine injection in gnotobiotic transgenic mice harboring human
      prototype c-Ha-ras genes.
AB  - We produced transgenic (Tg) gnotobiotic (GB) mice carrying human prototype c-Ha
      ras genes and compared the incidence of colorectal tumors induced by 1,2
      dimethylhydrazine (DMH) injection. At 7 to 11 weeks of age, germfree (GF) CB6F1
      Tg Hras2 mice were inoculated with various mouse fecal suspensions or mixtures of
      bacteria isolated from mouse feces. Three weeks after bacterial inoculation, DMH
      was administered by subcutaneous injection at 20 mg per kg body weight for 20
      weeks. Mice were euthanized 5 weeks after the last injection to investigate the
      number of colorectal tumors. The incidence of colorectal tumors was high in both
      Tg- and non-Tg-GF mice (100%). In Tg-specific pathogen-free (SPF) mice and Tg-GB
      4 mice associated with basic mouse flora consisting of Escherichia coli,
      lactobacilli, Bacteroides and clostridia, the incidence of colorectal tumors was
      as high as that in GF mice. In Tg-SPF mice, the tumor score was higher than in Tg
      GF mice (p < 0.01), but no colorectal tumors were detected in non-Tg groups of
      SPF, and the tumor incidence was remarkably low in non-Tg-GB-4 mice. The tumor
      incidence and score in Tg- and non-Tg-GB mice varied depending on the bacterial
      combination in their intestine. These results indicate that the presence of human
      c-Ha-ras genes and intestinal bacteria substantially modify colorectal
      tumorigenesis induced by DMH.

PMID- 9606422
TI  - Tissue differences in protein synthesis of the budgerigar (Melopsittacus
      undulatus).
AB  - In a series of experiment to elucidate the rule of amino acid requirements in the
      fowls from small to large ones, the fractional synthesis rates (FSR) of protein
      were determined to collect basal data on protein and amino acid metabolism in
      budgerigars as a small bird. Twenty young adult budgerigars were injected with
      0.1 ml/10 g body weight containing 40 microCi/100 mumol phenylalanine/ml in a
      wing vein, and killed at 2 and 10 min after the injection. The FSR in the whole
      body, liver, proventriculs and gizzard, intestine and breast muscle were
      determined. The FSR were not the same in all tissues, and estimated values were
      highest in the liver (104.7), and followed by the intestines (68.0), whole body
      (55.2), proventriculs + Gizzard (46.8), heart (35.8) and breast muscle
      (26.9%/day).

PMID- 9606423
TI  - Improvement of a mouse feeder for chemical toxicology testing.
AB  - A mouse feeder in common use in the US was modified to eliminate spillage,
      contamination by excreta and formation of food aggregates. The improved feeder
      consists of a glass jar which holds 100 g of meal-type feed, an inner metal mesh
      tube, a marble placed inside the inner mesh tube, and a snap-on metal lid. Female
      mice [B6C3F1 and CD-1(ICR)] were housed 5 animals/cage. Only slight contamination
      by feces, but not by urine, was observed in a 13-week feeding study with Japanese
      meal-type food and the improved feeder. Food spillage also decreased. Food
      consumption was significantly higher in cages with the conventional Japanese
      feeder than in the improved one, but no difference was observed between the two
      feeders in body weight gain.

PMID- 9606424
TI  - Strain differences in glutathione metabolism in the erythrocyte from Syrian
      hamster.
AB  - Strain differences in erythrocyte glutathione (GSH) metabolism were studied in
      five inbred strains of Syrian hamster. Significant strain differences were found
      in the GSH level, rate of GSH regeneration, and the activity of hexokinase (HK).
      The rate of GSH regeneration did not correlate with the activity of HK. A gender
      difference was observed in the activity of HK. Our results indicate the
      possibility that Syrian hamster would be a model for studying the strain
      differences in the erythrocyte GSH metabolism.

PMID- 9606425
TI  - Spontaneous osteoarthritic lesions in a new mutant strain of the mouse.
AB  - In our laboratory, mice showing signs of osteoarthritic lesions with cinnamon
      colored (yellowish-brown) hair were discovered in a colony of B6C3F1 mice. This
      mouse is characterized by tiptoe walking and swelling and ankylotic changes in
      the ankle joint. As to radiographic findings, osteoarthritic changes, such as
      erosion and/or fusion of the bone tissue, were evident in the ankle joints.
      Histopathological characteristics included irregularity of articular surfaces
      caused by fissuring and/or erosion with degeneration of articular cartilage, as
      well as osteophytes with abnormal proliferation of chondrocytes in joint margin
      regions. Subsequently, ankylotic changes in the ankle joints were completed in
      the formation of a cartilaginous bridge and fusion of articular cavity with
      abnormal proliferation of cartilaginous or bone tissues. This mouse strain may
      provide an additional animal model that is valuable in the study of human
      osteoarthritis (OA).

PMID- 9606426
TI  - Contamination of mouse-adapted influenza virus with Sendai virus.
AB  - In our laboratory animal facility, Sendai virus (HVJ) contamination occurred in a
      negative flow rack used for experimental infection with 4 strains of mouse
      adapted influenza virus (Inf.V). Anti-HVJ antibody (Ab) was detected in 35/42
      mice in the rack. To specify the strain of Inf.V contaminated with HVJ,
      experimental infection was performed by using A, B and D strains of Inf.V in each
      vinyl isolator. Anti-HVJ Ab was detected in all mice infected with A strain at
      day 28 post-infection. As a result of experimental infection with A strain of
      Inf.V which was treated with anti-HVJ mouse serum, the virus suspension was
      determined not to contain HVJ and allowed for experimental use in our facility,
      Since then, HVJ contamination has not occurred in our facility.

PMID- 9606427
TI  - Mapping of the gene for rat telomerase protein component 1 (Tlp 1) to chromosome
      15.

PMID- 9606428
TI  - [Characteristics of animal models of diabetes mellitus].

PMID- 9606429
TI  - [Characteristic feature of diabetes mellitus in GK rats].

PMID- 9606430
TI  - [Diabetes mellitus models in OLETF rats].

PMID- 9606431
TI  - [Genetic analysis of IDDM in NOD mice].

PMID- 9606432
TI  - [New diabetes mellitus models: gene targeting].

PMID- 9606433
TI  - Functional magnetic resonance imaging (fMRI) visualises the brain at work.
AB  - Functional Magnetic Resonance Imaging (fMRI) is a recent MRI technique capable of
      visualising neuronal activity in humans in a non-invase way. The technique
      visualises the physiological changes in oxy- and deoxyhemoglobin concentration
      changes in small cortical blood vessels upon neuronal activation without the need
      for radiation or the administration of contrast media or radioactive tracers. The
      spatial accuracy of the technique is of the order of millimeters and the temporal
      resolution of the order of one second. The concept has captured the interest of
      neuroradiologists as well as neuroscientists, who now have a means to visualise
      their theories in human volunteers. In the clinical environment the non-invasive
      studies should aid neurosurgeons in adopting a safe course into the brain and
      assist neurologists in unraveling neurological hypotheses. This report describes
      the technical principals of fMRI and presents some of our clinical results on the
      mapping of several cortical functions, such as motor, auditory and language
      functions, in a large group of patients.

PMID- 9606434
TI  - Impaired early visual processing in disorganised schizophrenia.
AB  - Topographic differences in flash/pattern shift VEP data are evaluated in paranoid
      (n: 38), disorganized (n: 23) and residual (n: 23) schizophrenic subtypes and
      compared to normal controls. Increased early P1 and a restricted diffusion of the
      late P2 responses suggest dopaminergic over- and cholinergic underactivity in
      paranoid and residual schizophrenia. A distinctive pattern N145 reflects well
      preserved attentional resources in the paranoid subtype. Latency increase and
      amplitude decrease of the pattern N145 concur with abnormal antisaccades
      documented in disorganized behaviour. VEP-data might help differentiate between
      schizophrenic subtypes.

PMID- 9606435
TI  - P300 after minor head injury (a follow-up examination).
AB  - BACKGROUND AND METHODS: The aim of the study was to examine whether--like in
      severe head injuries--the endogenous evoked potential P300 is influenced by minor
      head injury (MHI) and how the eventual abnormalities develop within a follow-up
      period of 8 weeks after trauma. Therefore we examined the cognitive auditory
      evoked potential P300 (latency, amplitude), the neurologic state and the
      performance in psychometric testing (Mini-Mental-State, Number Connection test
      part A and B) in 15 patients within the first 24 hours as well as 1, 3 and 8
      weeks after MHI. The P300 results were compared to the age-related normal ranges
      under consideration of the intra-individual variability. For both parameters
      normative values were established before in our own laboratory. RESULTS: For the
      patient group as a whole the mean values for P300 latency and amplitude were
      always within the age-related normal range and normal intra-individual long-term
      variability of healthy controls, respectively. Significant posttraumatic
      prolongations of P300 latency were exclusively observed in the only 20% of our
      patients with clinically suspected posttraumatic organic brain syndrome. These
      prolongations of latency decreased during follow-up and on the last examination
      the latencies were normalised. Compared to psychometric tests, P300 latency seems
      to be more sensitive in early detection of cerebral dysfunction. CONCLUSIONS: We
      conclude that, in contrast to severe head injury, in general the P300 is not
      affected by minor head injury. If there are clinical signs of organic brain
      syndrome following MHI posttraumatic prolongation of P300 latency is a marker of
      cerebral dysfunction and may serve as a valuable parameter for follow-up
      examination and documentation.

PMID- 9606436
TI  - Radiological follow-up in encapsulated intracerebral hematoma mimicking
      intratumoural bleeding.
AB  - Chronic encapsulated intracerebral hematoma, which is usually seen in young,
      normotensive patients, is rare, but has been reported with increasing frequency
      in recent years. In this report, we have presented a case of encapsulated
      intracerebral hematoma mimicking intratumoural bleeding with its whole natural
      radiological progression. A 55 year-old man developed a progressive neurological
      deficit one month after hospitalisation due to spontaneous intracerebral
      hemorrhage. Cranial CT and MR demonstrated a ring-shaped hemorrhagic lesion with
      mass effect and perifocal edema. After 15 months, there was marked improvement in
      clinical findings, and imaging techniques showed marked resorption of the mass.
      Radiological findings of spontaneous resolution of the encapsulated intracerebral
      hematoma are described for the first time in the reported case. Encapsulated
      intracerebral hematoma can present much like a brain tumour and should be
      considered in the differential diagnosis of other hemorrhagic space-occupying
      lesions.

PMID- 9606437
TI  - Drug-induced spongiform leucoencephalopathy, a case report with review of the
      literature.
AB  - A nineteen year-old girl developed rhabdomyolysis and central pyrexia after the
      ingestion of multiple drugs: amphetamines, benzodiazepines, methadone, ethanol,
      and cocaine. On admission, the patient was deeply comatose and during the
      hospitalisation asymmetrical spastic quadriparesis was noted. Brain biopsy was
      diagnostic of spongiform leucoencephalopathy. A review of the literature
      concerning drug-induced spongiform encephalopathy revealed a large amount of
      heroin-induced cases. The role of cocaine, however, is less well described. After
      prolonged hospitalisation, our patient improved clinically and radiologically and
      could be transferred to a rehabilitation center.

PMID- 9606438
TI  - Cerebral venous thrombosis in pregnancy: the role of protein S deficiency.
AB  - We report a 20 year-old, 28 week-pregnant woman, who developed superior sagittal
      sinus thrombosis, associated with a decreased free protein S level. Her father,
      who had been a stroke victim, had also significantly lower level of protein S. In
      very rare cases, a congenital or acquired protein S deficiency leads to cerebral
      venous thrombosis. The detection of such abnormalities has major practical
      consequences for the long-term management of patients to prevent further
      thrombotic episodes.

PMID- 9606439
TI  - [Lumboradiculalgia revealing malignant non-hodgkin's lymphoma. Report of two
      cases].

PMID- 9606440
TI  - Clinical-pathological conference.

PMID- 9606441
TI  - A horizontal pointing manoeuvre for clinical evaluation of patients with
      cerebellar disease.

PMID- 9606442
TI  - Low dosage of pergolide in the treatment of restless legs syndrome.

PMID- 9606443
TI  - Tamoxifen reduces risk of breast cancer in high-risk women.

PMID- 9606444
TI  - FDA approves oral therapy for erectile dysfunction.

PMID- 9606445
TI  - Risedronate released for Paget's disease.

PMID- 9606446
TI  - Study strengthens case against using aspirin to prevent preeclampsia.

PMID- 9606447
TI  - Customer service key to satisfaction with managed care plans.

PMID- 9606448
TI  - Not enough physicians identify smokers, advise cessation.

PMID- 9606449
TI  - Improving documentation of preoperative antimicrobial prophylaxis.

PMID- 9606450
TI  - Reducing expenditures for statin-type lipid-lowering agents.

PMID- 9606451
TI  - Olanzapine: a serotonin-dopamine-receptor antagonist for antipsychotic therapy.
AB  - The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug
      interactions, dosage and administration, and cost of olanzapine are reviewed.
      Olanzapine is a serotonin-dopamine-receptor antagonist indicated for use in the
      treatment of schizophrenia and other psychotic disorders. The affinity of
      olanzapine for neuroreceptors is similar to that of clozapine. The drug is well
      absorbed from the GI tract; food has no effect. Olanzapine is more effective than
      placebo and equal to haloperidol in reducing psychotic symptoms on two rating
      scales. However, unlike typical dopamine-receptor antagonists used for
      antipsychotic therapy, olanzapine is more effective in reducing the negative
      symptoms of schizophrenia. The most frequent adverse drug reactions (ADRs)
      associated with olanzapine are somnolence, agitation, insomnia, and headache.
      Constipation and dry mouth occur as dose-dependent ADRs. Unlike clozapine,
      olanzapine does not cause agranulocytosis. No cases of tardive dyskinesia or
      neuroleptic malignant syndrome have been reported. Olanzapine has been associated
      with slight increases in hepatic transaminases. More study is needed to determine
      whether olanzapine interacts significantly with other drugs. The recommended
      starting dosage is 5-10 mg orally once daily. Efficacy beyond six weeks has not
      been evaluated; patients treated for longer than six weeks should be periodically
      reassessed. Olanzapine costs about 10 times more than typical antipsychotics
      because a generic version is not available; however, olanzapine costs less than
      clozapine therapy and may cost less than haloperidol in terms of total health
      care costs. Olanzapine offers an effective alternative for treating schizophrenia
      and has a favorable adverse-effect profile.

PMID- 9606452
TI  - System for exchanging information among pharmacists in different practice
      environments.
AB  - A system for exchanging patient information among hospital, long-term-care (LTC),
      and ambulatory care pharmacies is described, and the influence of that system on
      pharmacist interventions is reported. Study sites consisted of three ambulatory
      care pharmacies, one LTC pharmacy, and one hospital in a small Midwestern city.
      Meetings were held by clinicians, the investigators, and hospital administrators
      to plan the information-exchange system. From January through June 1996, patients
      admitted to the hospital were checked to see if they came from a participating
      (source) pharmacy; if so, they were randomly assigned to experimental and control
      groups. The hospital requested preadmission information from the source pharmacy
      for experimental group patients and did not do so for control patients. After the
      information arrived, the hospital pharmacists could use it to identify and
      document drug therapy problems. When an experimental group patient was
      discharged, the hospital sent information to the appropriate source pharmacy. A
      total of 156 patients were enrolled in the study. Complete information transfer
      occurred for 75% of experimental group patients. Significantly more experimental
      group patients than control patients had at least one in-hospital pharmacist
      intervention recorded. Similarly, in the ambulatory care pharmacies (but not the
      LTC pharmacy) significantly more interventions per patient were documented for
      the experimental group. Hospital and ambulatory care pharmacists documented more
      interventions for patients about whom information had been supplied than for
      patients for whom that information had not been supplied. No difference in
      intervention rates was observed for LTC pharmacists, who were already being
      supplied information by the LTC facilities about patients discharged from the
      hospital.

PMID- 9606453
TI  - Patient satisfaction with delivery of products and information by an ambulatory
      care pharmacy.
AB  - A survey for assessing ongoing patient satisfaction with ambulatory care
      pharmaceutical services was developed for and tested in a veterans population;
      acquiescence response to survey items and desire for potential future services
      were measured. A questionnaire based on key aspects of patient satisfaction
      described in the literature was distributed to 1451 patients visiting an
      ambulatory care pharmacy prescription-pickup window during five consecutive days
      in 1994. Patients were asked about current services and the desirability of
      potential future services. Patients indicated their responses to statements about
      current services. Acquiescence response (the tendency to agree with statements
      regardless of content) was measured by using matched pairs of contradictory
      statements. The response rate was 48.3%. Patients' mean +/- S.D. overall
      satisfaction with current services was 3.7 +/- 1.1. The responses of 72.0% of
      patients exhibited no contradictions. The potential new service wanted most by
      respondents was availability of a pharmacist to talk with patients by telephone;
      seeing a pharmacist in the clinic instead of a physician for drug-related
      problems was wanted least by respondents. Veterans responding to a survey of
      satisfaction with ambulatory care pharmaceutical services had a low tendency to
      agree with statements regardless of content. The survey can be used to assess
      veterans' ongoing satisfaction.

PMID- 9606454
TI  - Opinions of disease management programs among medical directors of managed care
      organizations.
AB  - Medical directors of managed care organizations (MCOs) were surveyed about their
      views on disease management programs in their facilities. A survey was mailed to
      600 MCO medical directors. The survey consisted of 14 Likert-type items related
      to disease management programs, 4 demographic items, and 1 item related to
      satisfaction. Seventy-nine usable surveys were received, for a net response rate
      of 14%. There were 48 medical directors (61%) with disease management programs at
      their MCO; 25 (52%) were working independently. A majority (71%) of programs were
      targeted at asthma. Seventy percent of the 48 medical directors were completely
      to somewhat satisfied and 13% dissatisfied to some extent with their disease
      management programs. Satisfaction was significantly related to the MCO's
      partnerships for these programs. A majority of medical directors agreed or
      strongly agreed that disease management programs could improve outcomes and
      decrease health care costs at their MCO, that an independent consultant could
      help analyze their MCO's prescription and medical data, and that they would be
      willing to accept grants or funds from pharmaceutical companies to initiate and
      support an independent disease management program at their MCO. MCO medical
      directors who responded to a national survey indicated that their organization
      could benefit from disease management programs, that internal resources might be
      insufficient to manage these programs, and that their MCO might be willing to
      contract with external organizations for support.

PMID- 9606455
TI  - National survey of training and credentialing methods in pharmacist-managed
      anticoagulation clinics.
AB  - A national survey of pharmacist-managed anticoagulation clinics was conducted to
      determine how pharmacists are trained to provide care in such clinics. In June
      1996 a survey was mailed to 177 pharmacist-managed anticoagulation clinics in the
      United States. A total of 128 surveys were returned (response rate, 72%). One
      hundred ten surveys representing 42 states and a variety of institutions were
      usable. Twenty-five (23%) of the 110 clinics offered an anticoagulation training
      program for their pharmacists. Most training programs had both didactic and
      experiential components and had been in existence for one to five years. Thirty
      two (29%) of the 110 responding clinics had at least one pharmacist who had
      completed the ASHP Research and Education Foundation's Anticoagulation Service
      Traineeship. Twenty-three of the 25 clinics with a training program required
      successful completion of the program before a pharmacist could practice in the
      clinic. The overall quality of pharmacists' performance was regularly assessed by
      22 of the 25 clinics. Most pharmacist-managed anticoagulation clinics in the
      United States do not offer formal training in anticoagulation therapy to
      pharmacists who practice in that setting.

PMID- 9606456
TI  - Stability of cisatracurium besylate in vials, syringes, and infusion admixtures.
AB  - The stability of cisatracurium besylate was studied. Cisatracurium (as besylate)
      2 mg/mL in 5- and 10-mL unopened vials and 10 mg/mL in 20-mL unopened vials, as
      well as 3 mL of solution from additional 2-mg/mL vials, repackaged in 3-mL sealed
      plastic syringes, was stored at 4 and 23 degrees C in the dark and in normal
      fluorescent room light. Admixtures of cisatracurium (as besylate) 0.1, 2, or 5
      mg/mL in polyvinyl chloride (PVC) minibags of 5% dextrose injection or 0.9%
      sodium chloride injection were stored at 4 and 23 degrees C in normal fluorescent
      room light. Triplicate samples for each storage condition were taken initially
      and at 1, 3, 5, 7, 14, 21, and 30 days; samples from vials were also removed at
      45 and 90 days. Solutions were stored in sterile vials at -70 degrees C and then
      thawed at room temperature before analysis of chemical stability by high
      performance liquid chromatography. Physical stability was assessed as well.
      Cisatracurium besylate was physically stable in all samples throughout the study.
      Cisatracurium (as besylate) 2 mg/mL exhibited drug losses at 23 degrees C in
      vials at 45 days and in syringes at 30 days. Cisatracurium (as besylate) 0.1, 2,
      and 5 mg/mL in 5% dextrose injection and in 0.9% sodium chloride injection was
      stable for at least 30 days at 4 degrees C, but substantial drug losses occurred
      at 23 degrees C. Admixtures prepared with cisatracurium (as besylate) 0.1 mg/mL
      and with 5% dextrose injection exhibited the greatest losses. Cisatracurium
      besylate was stable in most samples for at least 30 days at 4 and 23 degrees C;
      admixtures containing cisatracurium (as besylate) 0.1 or 2 mg/mL exhibited
      substantial drug loss at 23 degrees C.

PMID- 9606458
TI  - ASHP policy-development process: opportunities for improvement. ASHP Ad Hoc
      Committee on Policy Development.

PMID- 9606457
TI  - Stability of torsemide in 5% dextrose injection.

PMID- 9606459
TI  - Hemolysis and renal failure associated with use of sterile water for injection to
      dilute 25% human albumin solution.

PMID- 9606460
TI  - Possible troglitazone-warfarin interaction.

PMID- 9606461
TI  - Aluminum contamination of neonatal parenteral nutrient solutions and additives.

PMID- 9606462
TI  - Replacement of divalproex sodium with valproic acid not clear-cut.

PMID- 9606463
TI  - Association between the diagnosis of mental retardation and socioeconomic
      factors.
AB  - Clinic data from the regional hospital in Cape Town, South Africa, over 4 years
      for 538 children with a diagnosis of mental retardation were examined in order to
      establish whether differences in mental retardation referral patterns existed
      between low and high socioeconomic areas. Results indicate that mild mental
      retardation referrals were underrepresented in low socioeconomic areas and that
      paramedical agencies were the primary referral source in these areas. Differences
      in mild mental retardation referral patterns by area over time may stem from
      service difficulties or variations in referral thresholds. Cross-cultural
      implications of the findings were discussed with relevance to the development of
      culturally sensitive community-based intervention programs.

PMID- 9606464
TI  - Prevalence of carpal tunnel syndrome among individuals with Down syndrome.
AB  - We examined occurrence of carpal tunnel syndrome in 48 patients with Down
      syndrome clinically and electrophysiologically. In the median nerve the distal
      latency to the abductor pollicis brevis muscle and the distal sensory nerve
      conduction velocity to digit II and III were recorded. As a control, we examined
      the ulner nerve. In the median nerve, a distal latency above 4.3 msec and sensory
      nerve conduction velocity below 50 m/sec were considered indicative of Carpal
      tunnel syndrome. Twenty seven patients (56%) had normal findings, 13 (27%) had
      both prolonged distal motor latency and reduced distal sensory nerve conduction
      velocity, and 8 patients (17%) had one of these signs, a much higher frequency
      than expected. Results show that prevalence of electrophysiological carpal tunnel
      syndrome is high in individuals with Down syndrome.

PMID- 9606465
TI  - Analysis of expenditures and outcomes of residential alternatives for persons
      with developmental disabilities.
AB  - Expenditures, staffing, and outcomes were examined for 116 adults with severe or
      profound mental retardation who moved from state institutions in Minnesota to
      various community living settings and a comparison group of 71 persons who
      remained institutionalized. Outcome variables included community access, social
      activities, community inclusion, family relationships, and choice. Comparison of
      participants' personal characteristics revealed no differences between groups,
      but several differences emerged when the community sample was grouped by
      residence size or public versus private ownership. Where necessary, covariance
      analysis was used to adjust for these preexisting differences. Community
      residences were less costly and had more favorable staffing and uniformly better
      outcomes than did institutions. Few outcome differences were evident between
      community residents when compared by residence size or service ownership.

PMID- 9606466
TI  - Mortality in persons with developmental disabilities after transfer into
      community care.
AB  - More than 2,000 persons with developmental disabilities have been transferred
      from California state institutions into community care in recent years. We
      investigated whether this has been accompanied by a change in mortality rates,
      using data on 1,878 clients moved since April 1993. Mortality rates were compared
      to those expected for comparable persons in institutions. Risk-adjusted mortality
      rates for movers exceeded institutional rates by 51%, p < .05. After removal of
      cancer deaths in both groups, this increased to 67%. The effect was largest
      shortly after the move and in the subjects who had moved most recently. The
      deinstitutionalization process in California appears to have resulted in a
      substantial increase in mortality, indicating the need to ensure continuous,
      consistent, and competent medical care and supervision in the community.

PMID- 9606467
TI  - Clinical study of the effects of age on the physical health of adults with mental
      retardation.
AB  - Physical disorders and pharmacotherapy for all 134 people with mental retardation
      ages 65 years and over living in Leicestershire, United Kingdom, were examined.
      Results were compared with a randomly selected group of 73 younger adults with
      mental retardation. Group comparisons revealed higher rates of urinary
      incontinence, immobility, hearing impairments, arthritis, hypertension, and
      cerebrovascular disease among the older group. The younger group had higher rates
      of dermatological disorders; congenital heart disease; ear, nose, and throat
      (ENT) disorders; and neurological disorders (excluding Parkinson disease). The
      older group took more drugs for physical illness. The effect of ageing on
      physical morbidity outweighs the effect of people with more severe mental
      retardation dying younger: Older people with mental retardation have significant
      physical health needs.

PMID- 9606468
TI  - Phenotypic involvement in females with the FMR1 gene mutation.
AB  - Fragile X syndrome is the most common from of inherited mental retardation.
      Approximately half of females with the full mutation have significant cognitive
      deficits, whereas females with the premutation do not. Phenotypic effects seen in
      281 females (IQs from 64 to 139) were analyzed. Results showed that females with
      the full mutation differ significantly from controls on selected anthropometric
      measurements, physical index score, and various behavioral features. Females with
      the premutation differed significantly from controls in regards to a few
      anthropometric measurements and the physical index score but not in behavioral
      features. These results suggest that phenotypic effects of the FMR1 mutation are
      not only common in females with the full mutation, but in females with the
      premutation as well.

PMID- 9606469
TI  - Validation of cardiovascular fitness field tests in children with mental
      retardation.
AB  - The validity of the 600-yard walk/run, the 20-m shuttle run, and a modified 16-m
      shuttle run was determined to measure aerobic capacity (VO2peak) in children with
      mild and moderate mental retardation. Practice sessions for all tests were
      conducted. All field tests were very reliable, and VO2peak was significantly
      related to them all. A stepwise multiple regression showed that field test
      performance, body mass index (BMI), and gender, but not age, were also
      significant predictors of VO2peak. All field tests were valid and reliable
      indicators of aerobic capacity, suggesting that these tests can be used to
      predict VO2max in children with mild and moderate mental retardation.

PMID- 9606470
TI  - Cultural factors enhancing resilience and protecting against maladjustment in
      African American adolescents with mild mental retardation.
AB  - Researchers have found elevated risk for maladjustment associated with being an
      African American adolescent in an urban environment as well as being an
      individual with mental retardation. The culturally relevant factors of ethnic
      identification, intergenerational support, and church support were investigated
      in relation to high risk exposure on maladjustment in 147 urban African American
      adolescents enrolled in EMR special education classes. Maladjustment was measured
      with both self- and parent-report. Risk exposure was measured in the personal,
      social, and community domains. Results indicate that presence of cultural factors
      were associated with better adjustment generally. Furthermore, ethnic
      identification appeared to protect adolescents exposed to high-risk conditions
      against experiencing significantly elevated maladjustment. Implications of
      culture on intervention and prevention were discussed.

PMID- 9606471
TI  - Impact of zidovudine plus lamivudine or zalcitabine on health-related quality of
      life.
AB  - OBJECTIVE: To assess the impact of treatment with zidovudine plus lamivudine or
      zalcitabine on health-related quality of life (HRQOL) in patients with HIV.
      DESIGN: HRQOL assessments were conducted as part of a double-blind, randomized,
      24-week (extended to 52 wk) efficacy and safety study. The Medical Outcomes Study
      HIV Health Survey (MOS-HIV), which assesses 10 physical and psychological domains
      of HRQOL, was self-administered by patients at baseline and at weeks 16, 32, 52,
      or at treatment discontinuation. SETTING: Twenty-one outpatient centers in the
      US, Canada, and Puerto Rico. PATIENTS: The study enrolled 254 HIV-positive
      patients (CD4+ 100-300 cells/mm3); 206 patients completed the MOS-HIV at baseline
      and at least once during treatment. Post hoc analyses stratified patients into
      two subgroups: AIDS (CD4+ < 200 cells/mm3) and non-AIDS (CD4+ > or = 200
      cells/mm3). INTERVENTIONS: Patients received zidovudine 200 mg three times daily
      plus one of the following: lamivudine 150 mg twice daily, lamivudine 300 mg twice
      daily, or zalcitabine 0.75 mg three times daily. MAIN OUTCOME MEASURE: Change in
      MOS-HIV scores from baseline to last completed questionnaire. RESULTS: Following
      an average of 36 weeks of treatment, there were statistically significant
      differences across treatment groups in mean change scores on the physical
      functioning, role functioning, and vitality scales, with stable or increased
      (improved) scores in the zidovudine plus lamivudine 150 mg group and decreased
      scores in the zidovudine plus zalcitabine and zidovudine plus lamivudine 300 mg
      groups for most scales. Post hoc analyses found that in the non-AIDS subgroup,
      only the zidovudine plus lamivudine 150 mg group had increases in mean MOS-HIV
      scores (on 8 of 10 scales); in the AIDS subgroup, all but two MOS-HIV scores (in
      the zidovudine plus zalcitabine group) decreased in all three treatment groups.
      CONCLUSIONS: These results suggest that, of the three combination therapies
      studied, zidovudine plus lamivudine 150 mg was most likely to maintain or improve
      HRQOL in HIV-positive patients.

PMID- 9606472
TI  - Concomitant prescribing of tranquilizers and hypnotics among patients receiving
      antidepressant prescriptions.
AB  - OBJECTIVE: To evaluate concomitant prescribing of tranquilizers and hypnotics in
      antidepressant treatment with particular focus on the relationship to drug class
      in patients prescribed antidepressant treatment for depressive disorders. DESIGN
      AND METHODS: Repeated cross-sectional surveys of Swedish physicians in ambulatory
      care from 1991 to 1996, including specialty practices. The participation rate was
      65-70%. RESULTS: Tranquilizers and hypnotics were prescribed in 36.1% of the
      visits in which the intention was to treat depression. Concomitant prescribing
      increased with the patient's age for all antidepressant drug classes. Women
      received more concomitant prescriptions than men when treated with nonselective
      monoamine-reuptake inhibitors (NSMRI), mainly tricyclic compounds. Psychiatrists
      prescribed more concomitant tranquilizers and hypnotics than other physicians,
      and general practitioners fewer, when treating depression with selective
      serotonin-reuptake inhibitors (SSRIs), mainly citalopram. A logistic regression
      model showed that the risk for concomitant prescribing was higher when an NSMRI
      was prescribed than with other antidepressants. CONCLUSIONS: Concomitant
      prescribing of tranquilizers and hypnotics was common among antidepressant
      treated patients. The most plausible reasons for the high rate of concomitant
      prescribing were the symptoms of the depression itself and/or the common
      comorbidity with anxiety disorders seen in this group of patients. The results of
      this study indicate that the concern about increased tranquilizer and hypnotic
      use among patients treated with SSRIs suggested in other studies seems to be
      unfounded in Sweden.

PMID- 9606473
TI  - Cost-effectiveness analysis of abciximab: a Canadian hospital perspective.
AB  - OBJECTIVE: To assess the cost-effectiveness of abciximab therapy versus
      traditional practice in high-risk patients receiving percutaneous transluminal
      coronary angioplasty (PTCA) from a Canadian hospital perspective. DESIGN: A
      predictive decision analytic model using published clinical and economic
      evaluations, as well as costs of medical care in Canada. SUBJECTS: High-risk PTCA
      patients as defined by the Evaluation of c7E3 for Prevention of Ischemic
      Complications trial and the c7E3 Fab Antiplatelet Therapy in Unstable Refractory
      Angina trial. INTERVENTIONS: Two treatment strategies were compared: (1)
      abciximab 0.25 mg/kg intravenous bolus 10 minutes prior to PTCA followed by
      abciximab 10 micrograms/min intravenous infusion for 12 hours after the
      procedure, and (2) no abciximab adjunctive therapy at the time of PTCA. Both
      treatment strategies were combined with intravenous heparin up to 100 units/kg
      bolus pre-PTCA followed by bolus doses for 1 hour after PTCA per the protocol.
      Cumulative outcomes were considered up to 6 months after initial PTCA. RESULTS:
      At 6 months, 29% of the patients in the abciximab treatment arm compared with 33%
      in the no abciximab arm achieved one of the primary events. The most common
      adverse event experienced was major bleeding at 4% in the abciximab treatment arm
      versus 1.6% in the no abciximab arm. The average cost per patient for each
      strategy was $3261 Can ($1 Can = $0.686 US) (abciximab arm) versus $2073 Can (no
      abciximab arm), resulting in an incremental cost-effectiveness ratio of $29,700
      Can per event-free patient. In univariate sensitivity analyses, the only
      controllable factor that changed the results of the cost-effectiveness outcome
      was the cost of abciximab. CONCLUSIONS: Although the use of abciximab as an
      adjunct to PTCA results in a reduction in event rates in high-risk patients
      compared with traditional treatment, there is an increased cost associated with
      this strategy.

PMID- 9606474
TI  - Leukocytoclastic vasculitis associated with clarithromycin.
AB  - OBJECTIVE: To report a possible case of leukocytoclastic vasculitis associated
      with clarithromycin therapy. CASE SUMMARY: An 83-year-old white woman was
      prescribed clarithromycin for pneumonia. Six days after her initial presentation,
      she developed lesions on her palms. Clarithromycin was discontinued at that time.
      The following day she developed purpuric eccymotic nonblanching lesions that
      primarily appeared on the lower extremities, buttocks, and abdomen. Colonoscopy
      revealed generalized erythema and edema of the bowel mucosa. Gastroscopy revealed
      duodenitis and gastritis, but no bleeding or ulceration. Skin biopsy of the
      lesions was compatible with leukocytoclastic vasculitis. Renal function was not
      affected, although hematuria was noted. All symptoms resolved after drug
      withdrawal and a short course of corticosteroids. DATA SOURCES: Searches were
      performed on MEDLINE, Embase, International Pharmaceutical Abstracts, and major
      adverse drug reaction databases to identify reports and articles discussing
      clarithromycin- and macrolide-induced leukocytoclastic vasculitis. DISCUSSION:
      Leukocytoclastic vasculitis is one category of drug hypersensitivity reactions
      characterized by distinctive patterns of perivascular inflammation. The case
      described here is consistent with the diagnosis of leukocytoclastic vasculitis,
      and is similar to the other single published case report associated with
      clarithromycin. CONCLUSIONS: Leukocytoclastic vasculitis induced by
      clarithromycin is a rare but serious potential adverse effect.

PMID- 9606475
TI  - Extravasation injury associated with low-dose dopamine.
AB  - OBJECTIVE: To describe the occurrence of extravasation in two patients receiving
      low-dose dopamine infusions. CASE SUMMARY: Intravenous dopamine was infused
      peripherally (in the antecubital fossa) to two patients in the cardiac intensive
      care unit in an attempt to enhance renal blood perfusion and urine output.
      Dopamine extravasation occurred in both patients while the low dose (< 3
      micrograms/kg/min) was infused. Significant local tissue injury was observed in
      both patients. DISCUSSION: Dopamine infusion can cause tissue ischemia or
      necrosis secondary to vasospasm and extravasation. Most of the case reports in
      the literature have occurred when relatively high doses of dopamine were infused.
      Only one reported extravasation-induced injury with low-dose dopamine. Although
      low-dose dopamine has a vasodilatory effect in selected tissues, high
      concentrations achieved locally as a result of extravasation can still cause
      severe vasoconstriction and ischemic tissue injury. CONCLUSIONS: Low-dose
      dopamine therapy should be administered with similar precautions as high-dose
      dopamine. A central intravenous access should be placed for dopamine infusion
      whenever possible. If this approach is not feasible, dopamine should be infused
      only peripherally through a long intravenous catheter into a large vein. A 5-cm
      angiocatheter that is 20 gauge or larger is recommended for peripheral dopamine
      infusion in our institution. The infusion site should be inspected frequently for
      early detection of extravasation, and changed to a central or a peripherally
      inserted central catheter as soon as possible, especially in patients at high
      risk for extravasation.

PMID- 9606476
TI  - Dapsone-induced methemoglobinemia.
AB  - OBJECTIVE: To report a case of methemoglobinemia in a patient receiving dapsone
      for prophylaxis of Pneumocystis carinii pneumonia (PCP). CASE SUMMARY: A 69-year
      old white woman was hospitalized to rule out sepsis. Two years prior to this
      admission, the patient received an orthotopic liver transplant after which she
      required hemodialysis three times weekly. Because of intolerance to trimethoprim/
      sulfamethoxazole and aerosolized pentamidine, she was prescribed dapsone therapy
      on hospital day 13, that was continued for 11 days. On hospital day 45 the
      patient received a cadaveric kidney transplant, and dialysis treatments were
      scheduled only as needed. One week after the transplant, dapsone therapy was
      resumed. Nine days into this course of dapsone, the patient developed dyspnea and
      oxygen desaturation of unknown etiology. The patient was evaluated for and
      diagnosed with methemoglobinemia. She received two doses of intravenous methylene
      blue and one dose of oral activated charcoal due to fluctuating methemoglobin
      concentrations. DISCUSSION: The elimination of dapsone is not completely
      understood. Several case reports of dapsone-induced methemoglobinemia are present
      in the literature. Most have occurred in patients who have accidentally or
      deliberately overdosed. Cases of methemoglobinemia in patients receiving
      therapeutic doses of dapsone are discussed. CONCLUSIONS: The growing numbers of
      immunosuppressed patients due to transplantation of HIV may result in increased
      dapsone use for the prevention of PCP. Clinicians should be aware of the adverse
      effects associated with dapsone therapy, and patients with dyspnea and hypoxemia
      of unclear etiology should be evaluated for methemoglobinemia.

PMID- 9606477
TI  - A mechanistic approach to antiepileptic drug interactions.
AB  - OBJECTIVE: To describe the primary types of antiepileptic drug (AED) interactions
      by using a mechanistic approach. DATA SOURCES: A literature search was performed
      using MEDLINE and bibliographies of recent review articles and published
      abstracts. DISCUSSION: AEDs are associated with a wide range of drug
      interactions, including hepatic enzyme induction and inhibition and protein
      binding displacement. Hepatic induction by AEDs affects the metabolism of a
      limited number of drugs with low therapeutic indices. Anticipation of induction
      interactions and careful clinical monitoring may alleviate potential problems.
      Most commonly used AEDs are eliminated through hepatic metabolism catalyzed by
      the cytochrome P450 (CYP) and uridine diphosphate glucuronosyltransferase (UGT)
      enzymes. Phenytoin, phenobarbital, and carbamazepine induce CYP and UGT enzymes.
      Lamotrigine is a weak inducer of UGT. Valproate is a broad-spectrum inhibitor of
      UGT enzymes, epoxide hydrolase, and CYP2C enzymes. Felbamate induces CYP3A4, but
      inhibits CYP2C19 substrates. Topiramate inhibits only CYP2C19 substrates.
      Ethosuximide, gabapentin, tiagabine, and vigabatrin are neither inducers nor
      inhibitors of drug metabolism. Hepatic enzyme inhibition usually occurs because
      of competition at the enzyme site. Knowledge of the specific metabolic enzymes
      involved in the metabolism of AEDs allows clinicians to predict potential
      interactions. CONCLUSIONS: By understanding the mechanisms of drug interactions,
      the pharmacist can play a key role in patient care by anticipating and preventing
      AED drug interactions.

PMID- 9606478
TI  - Treatment and prophylaxis of disseminated Mycobacterium avium complex in HIV
      infected individuals.
AB  - OBJECTIVE: To review the pathophysiology, epidemiology, treatment, and
      prophylaxis of disseminated Mycobacterium avium complex (MAC) infection in HIV
      infected individuals. DATA SOURCES: A MEDLINE (January 1966-July 1997) and
      AIDSLINE (January 1980-July 1997) search of basic science articles pertinent to
      the MAC infection in HIV-infected patients. STUDY SELECTION AND DATA EXTRACTION:
      All articles were considered for possible inclusion in the review. Pertinent
      information, as judged by the authors, was selected for discussion. DATA
      SYNTHESIS: The organism, epidemiology, and pathophysiology of disseminated MAC
      are discussed for background. A review of clinical trials for the treatment and
      prophylaxis of disseminated MAC are presented, along with unresolved issues
      concerning these topics. CONCLUSIONS: The incidence of disseminated MAC has
      increased dramatically with the AIDS epidemic. The infection can lead to
      increased morbidity and mortality in HIV-infected patients. Treatment regimens
      for patients with a positive culture for MAC from a sterile site should include
      two or more drugs, including clarithromycin. Prophylaxis against disseminated MAC
      should be considered for patients with a CD4 cell count of less than 50/mm3.

PMID- 9606479
TI  - Glucosamine.
AB  - OBJECTIVE: To review the pharmacology and pharmacokinetics of glucosamine and
      critically evaluate currently available literature regarding its safety and
      efficacy. DATA SOURCE: A MEDLINE search was conducted between January 1965 and
      May 1997. Key words used in the search were osteoarthritis, osteoarthrosis,
      gonarthrosis, and glucosamine. In addition, references cited in articles obtained
      from the MEDLINE search were reviewed for additional literature. STUDY SELECTION
      AND DATA EXTRACTION: All articles were considered for inclusion in the review.
      Articles were excluded from critical evaluation for lack of randomization, lack
      of a control group, 30 or fewer study participants, inconsistent treatment
      regimen, incomplete dosing information, or incomplete reporting of results. DATA
      SYNTHESIS: Osteoarthritis affects approximately 12% of the US population; the
      incidence increases with increasing age. Currently used pharmacologic treatments,
      including acetaminophen and nonsteroidal antiinflammatory drugs, do not slow or
      reverse the degenerative process in osteoarthritis. Glucosamine has recently
      received a great deal of attention from the public as a potential treatment of
      osteoarthritis, prompting healthcare professionals to investigate its clinical
      usefulness and potential for adverse effects. The drug has been proposed to stop
      and possibly reverse the degenerative process in osteoarthritis. Following
      absorption of an oral dose, glucosamine is incorporated into plasma proteins
      during first-pass metabolism, resulting in 26% bioavailability. Unbound
      glucosamine is concentrated in the articular cartilage. Each of the three
      critically evaluated studies reported a decrease in the symptoms of
      osteoarthritis (e.g., decreased Lequesne index, decreased pain severity,
      increased range of motion) for the glucosamine group, which was greater than that
      obtained in the control group. Flaws in study design, however, prevent the use of
      these results in modifying current clinical practice. Reported short-term adverse
      effects include mild gastrointestinal problems, drowsiness, skin reactions, and
      headache. CONCLUSIONS: Improvement in the symptoms of osteoarthritis associated
      with the use of glucosamine has been observed in clinical trials; however, those
      trials have flaws in design and data analysis. Further research needs to be
      conducted before glucosamine can be recommended as a treatment for
      osteoarthritis.

PMID- 9606480
TI  - Glucosamine sulfate for osteoarthritis.
AB  - OBJECTIVE: To characterize the usefulness of glucosamine sulfate in the treatment
      of patients with osteoarthritis (OA). DATA SOURCES AND STUDY SELECTION: Pertinent
      citations were identified via a MEDLINE search (January 1975-March 1997). Only
      trials available in the English language involving human subjects, OA, and
      glucosamine sulfate were selected for review. DATA SYNTHESIS: OA is the most
      common form of arthritis and represents a major cause of morbidity and disability
      in the elderly. The main symptom of OA is pain and most of the commonly
      prescribed medications (e.g. acetaminophen, nonsteroidal antiinflammatory drugs)
      have been targeted at relieving the pain. Some of these medications have serious
      adverse effects and do not necessarily change the natural course of the disease.
      Glucosamine sulfate, a nutritional supplement, has recently emerged as an
      alternative treatment option for patients with OA. The beneficial effects of this
      chondroprotective agent have been reported to reverse or at least stop the
      progression of the disease without inducing serious adverse effects. Limited data
      from short-term human trials suggest that glucosamine sulfate administered
      orally, intravenously, intramuscularly, and intraarticularly may produce a
      gradual and progressive reduction in joint pain and tenderness, as well as
      improved range of motion and walking speed. Results of the trials have also shown
      that glucosamine has produced consistent benefits (> 50% overall improvement in
      symptom scores) in patients with OA and that, in some cases, it may be equal or
      superior to ibuprofen in controlling symptoms. CONCLUSIONS: There is evidence
      that glucosamine sulfate may provide pain relief, reduce tenderness, and improve
      mobility in patients with OA. Most of the current data, however, are derived from
      the European and Asian literature and there are no studies supporting the use of
      this agent in the US. The studies published to date have been done in small
      numbers of patients; adequate long-term trials examining the safety, efficacy,
      and optimal dosage requirements of glucosamine sulfate are lacking. Most of the
      available clinical data are difficult to interpret due to serious deficiencies in
      study design. Furthermore, studies evaluating the appropriate place of
      glucosamine sulfate in the therapeutic armamentarium of OA remain to be done.

PMID- 9606481
TI  - Low-molecular-weight heparins in the treatment of deep-vein thrombosis.
AB  - OBJECTIVE: To compare the characteristics and clinical efficacy of low-molecular
      weight heparins (LMWHs) and unfractionated heparin (UFH) in the treatment of deep
      vein thrombosis (DVT). Adverse effects, dosing, and cost issues are also
      discussed. DATA SOURCES: A MEDLINE search (January 1984-October 1997) was used to
      identify pertinent French and English literature, including clinical trials and
      reviews on LMWHs and their use in DVT. STUDY SELECTION: Trials comparing
      dalteparin, enoxaparin, tinzaparin, and nadroparin with UFH were selected. As
      studies were numerous, only randomized trials including more than 50 patients
      were reviewed. Moreover, all patients studied had a first episode of symptomatic
      DVT confirmed by objective tests (i.e., venography, duplex ultrasonography,
      impedance plethysmography). Clinical efficacy and safety of LMWHs were assessed
      in these trials. DATA EXTRACTION: Results pertaining to venographic assessment,
      recurrent thromboembolism, total mortality, and bleeding complications were
      extracted from the selected studies. DATA SYNTHESIS: Compared with UFH, LMWHs
      have a longer plasma half-life, better subcutaneous bioavailability, more
      predictable anticoagulant response, and require less intense laboratory
      monitoring. Most trials demonstrate comparable effects on thrombus extension and
      incidence of recurrent thromboembolism. Compared with UFH, LMWHs do not alter
      total mortality. Although animal trials predict a lower hemorrhagic potential for
      LMWHs, the incidence of bleeding complications is generally similar to that
      observed with UFH. Outpatient management of DVT with LMWHs has shown comparable
      safety and efficacy with inpatient UFH use but a shorter hospital stay.
      CONCLUSIONS: Because LMWHs are as safe and as effective as UFH, and because of
      their more convenient method of administration, they can be considered valuable
      alternatives for the treatment of DVT. Savings generated by less intensive
      laboratory monitoring and the possibility of early hospital discharge and
      outpatient therapy may outweight the higher acquisition cost of LMWHs.

PMID- 9606482
TI  - Glucosamine for osteoarthritis: cure or conundrum?

PMID- 9606483
TI  - Intrinsic staining of teeth secondary to tetracycline.

PMID- 9606484
TI  - Exacerbated hyperglycemia associated with nelfinavir.

PMID- 9606485
TI  - False-positive urine melanin pigment reaction caused by rifampin.

PMID- 9606486
TI  - Possible association between donepezil and worsening Parkinson's disease.

PMID- 9606487
TI  - Lack of CNS penetration of docetaxel in a patient with leptomeningeal
      carcinomatosis.

PMID- 9606488
TI  - Useful patient information on prescription drugs.

PMID- 9606489
TI  - [Natural and induced variability of pathogen, producing antifungal antibiotic,
      imbrimycin].
AB  - Natural and induced variation of Streptomyces imbricatus LIA 0112, an organism
      producing imbricin, a nonpolyene antifungal antibiotic, was studied. The culture
      was shown to be homogeneous by the morphological and cultural properties and
      consisted of one (rarely two) morphological type depending on the medium
      composition. The effect of some mutagens such as UV light, N-nitroso-N-methyl
      biuret in a concentration of 0.05 per cent and 1,4-bisdiazoacetyl butane in a
      concentration of 0.1 per cent on the actinomycete culture was investigated. It
      was found that the imbricin-producing culture was stable to the effect of both
      the physical and chemical mutagens. As a result of multistep selection of the
      actinomycete culture its productivity increased by 22 per cent.

PMID- 9606490
TI  - [Novel mathematical approach to determination of antibiotics concentration by
      agar diffusion method. Analysis of graphical, table and mathematical options of
      relative biological activity estimation].
AB  - Several varieties of relative biological activity estimation are comparatively
      analyzed and illustrated by an example of tylosin. For visual demonstration the
      estimates with the equation of a straight line are represented graphically. It is
      concluded that the design equations in the State Pharmacopeia XI (USSR) should be
      respectively replaced. The advantages of the variety for the biological activity
      estimation with the one-point intercept form of the equation of a straight line
      are illustrated by particular examples.

PMID- 9606491
TI  - [Antibiotic sensitivity of Vibrio cholerae 01 isolated from humans].
AB  - Antibiotic susceptibility of 1479 Vibrio cholerae 01 strains isolated from humans
      between 1991 and 1995 was studied. The antibiotics used belonged to different
      chemical groups. The assay method was that of serial dilutions in solid media.
      The isolates showed high susceptibility to tetracyclines, gentamicin,
      erythromycin, rifampicin, ampicillin, carbenicillin and cefazolin. The
      susceptibility to kanamycin and monomycin was moderate and that to
      chloramphenicol, streptomycin and polymixin B was low. The time and area
      peculiarities of the circulating cultures were observed. The susceptibility of
      the isolates was either changing or unchanging. The constant susceptibility
      levels were detected with respect to gentamicin, erythromycin, monomycin,
      kanamycin, streptomycin and polymyxin B. The susceptibility changing in time was
      shown with respect to tetracyclines, rifampicin and chloramphenicol. A gradual
      increase in the resistance to betalactams with greater numbers of the plasmid
      resistance pattern strains was recorded. Regular surveillance of the changes in
      the V.cholerae 01 antibiotic susceptibility is needed to timely correct the
      treatment and prophylaxis regimens.

PMID- 9606492
TI  - [Improvement of effectiveness of antibiotic therapy by pyrimidine derivatives in
      reparative regeneration of skin in rats].
AB  - It was shown on noninbred albino rats with various affections of the skin that
      pyrimidine derivatives stimulated the skin reparative regeneration and increased
      the efficacy of antibiotic therapy of Staphylococcus and Proteus infected wounds.
      The therapeutic effect of 2-methyl-4-amino-6-oxypyrimidine was much higher than
      that of oxymethyluracil or methyluracil. The pyrimidine derivatives proved to be
      universal accelerators for reparative regeneration, were compatible with
      antibiotics and increased their efficacy.

PMID- 9606493
TI  - [Protective properties of doxycycline, rifampicin and sisomycin in experimental
      pulmonary tularemia of albino mice].
AB  - The protective effects of doxycycline, rifampicin and sisomicin were compared in
      a multifactor experiment with animal infection induced by finally dispersed
      aerosol of a virulent strain of the European variant of the tularemia causative
      agent and the optimal regimens for the antibiotic use were determined. By the
      values of the protective effect rifampicin and sisomicin were shown to provide a
      high percentage of the animal survival: more than 80 and up to 50-70 per cent of
      the animals survived when the aerosol infective doses were 100 and 10,000 LD50,
      respectively. A characteristic feature of doxycycline was its activity only in
      the infection induced by low doses of the biological agent. The optimal course of
      the antibiotic therapy in inhalation tularemia was 6 to 8 days. The interval of 1
      to 3 days between the infection and the therapy start had no significant effect
      on the protective efficacies of the antibiotics.

PMID- 9606494
TI  - [Pathomorphological changes in albino mice infected with plague and treated with
      cefotaxime].
AB  - Pathomorphological and bacteriological changes in albino mice infected with
      plague and treated with cefotaxime were investigated. The control animals which
      died within 3 days had structural changes characteristic of generalized plague
      with lesions in the infection site, regional lymph nodes, spleen, liver and
      lungs. The plague microbe was isolated from the tissues of all the organs and
      blood. The animals treated with cefotaxime (200 mg/kg for 7 days) survived. The
      histological examination conclusively demonstrated the absence of the changes
      characteristic of generalized plague in their internal organs. The infection
      process was mainly restricted by the primary complex and was strictly localized.
      The tissue reaction around the focus in the second part of the experiment
      developed in accordance with the productive type inflammation followed by the
      organization and cicatrization. In the bacteriological investigation the plague
      causative agent was detectable during the first days of the treatment in the site
      of the infection. During the subsequent days the plague microbe was not detected.

PMID- 9606496
TI  - [Etiotropic therapy of brucellosis].

PMID- 9606495
TI  - [Effect of metronidazole on luminol dependent chemiluminescence of neutrophils in
      whole blood of patients with chlamydial infection].
AB  - In vivo effect of metronidazole on the active oxygen production by neutrophils in
      the peripheral blood of patients with urogenital chlamydial infection (9 females
      and 7 males) was studied with the use of luminol dependent chemiluminescence.
      Metronidazole was administered orally in a dose of 250 mg twice a day for 10
      days. Blood for the specimens was collected prior to the treatment and on the
      next day of the treatment course completion. No effect on the spontaneous and
      zymozan or phorbol-12-myristate-13-acetate stimulated chemiluminescence was
      observed, although a significant increase in the chemiluminescence indices was
      stated in 3 females and 1 male. It was suggested that the changes in the
      individual values of the neutrophil chemiluminescence after the treatment were
      associated with the influence of metronidazole and/or its metabolites on the
      blood cells and with different activity of the host enzymes participating in the
      drug biotransformation.

PMID- 9606497
TI  - [Search for microorganisms among collectable bacterial strains capable of
      transforming nucleosides into virazole].
AB  - The ability of bacterial cultures to transform nucleosides to virazole, a
      riboside with antiviral activity, was studied. Qualitative and quantitative
      methods for estimation of the microbial activity in the biotransformation
      reaction were designed. A qualitative rapid method for analysis of a large number
      of cultures was developed. Thirty nine collection strains were tested for their
      capacity to bioconvert nucleosides to virazole. Intact cells grown in a liquid
      medium were used as a source of purine nucleoside phosphorylase. Purine
      nucleosides such as adenosine, inosine, guanosine and 30-percent ribose solution
      resulting from the riboxin hydrolysis were tested as the ribose donors. The best
      results were obtained with the ribose solution. No distinct correlation between
      the genus of the microorganisms and their capacity for bioconversion of certain
      substrates was observed. Several cultures which showed stable and high results
      with respect to all the tested substrates were detected.

PMID- 9606498
TI  - [Novel L-glutamate oxidase producing organisms: Streptomyces litmocidini and
      Streptomyces cremeus].
AB  - Two novel strains i.e. Streptomyces cremeus 510 and Streptomyces litmocidini 447
      producing L-glutamate oxidase were isolated from soil samples and identified.
      Mathematical design of the experiments made it possible to optimize the
      fermentation medium composition which provided at least a 5-fold increase of the
      strain L-glutamate oxidase activity by comparison with the initial activity in
      the standard medium.

PMID- 9606500
TI  - [Dynamics of interferon induction in albino mice by interferon inducer ridostin
      administered by various routes].
AB  - The time dependence of interferon production in blood, tissues of the respiratory
      tract, brain and olfactory tract of mice BALB/c was investigated after
      administration of the interferon inductor ridostin by various routes.
      Intraperitoneal injection of ridostin in a dose of 5 mg/kg induced intensive
      accumulation of interferon in the blood serum with the peak in 8 hours (2560
      U/0.2 ml) while no interferon was detected in the tissues of the respiratory
      tract and brain of the animals. Intracerebral injection of ridostin in the same
      dose induced accumulation of interferon in both the tissues of the brain (maximum
      160 U/0.2 ml in 24 hours) and the blood serum (maximum 1280 U/0.2 ml in 8 hours).
      After respiratory administration of ridostin interferon was detected only in the
      site of the administration in the tissues of the upper respiratory tract and
      lungs of the mice.

PMID- 9606499
TI  - [Analysis of genome rearrangements in Streptomyces kanamyceticus mutants].
AB  - Studies with the use of pulsed electrophoresis showed that Asel and Dral
      restriction endonucleases segregated chromosomal DNA of the initial strain
      Streptomyces kanamyceticus 1 into 16 and 12 fragments, respectively. The total
      size of the strain chromosomal DNA was from 7715 (the total of the Dral fragment
      sizes) to 7788 kb (the total of the Asel fragment sizes). Chromosomal DNA
      rearrangements were detected in the unstable Kan- mutant kan12 as well as in
      mutant genR10 which was characterized by higher resistance to kanamycin and
      gentamicin. As compared to DNA of the initial strain S.kanamyceticus 1 and the
      stable mutant kanC782, mutant kan12 lacked 98-kb and 220-kb Asel fragments and
      contained additional 297-kb and 450-kb fragments. DNA of genR10 lacked 420-kb
      Asel fragment but contained an additional 450-kb fragment. Kan12 and genR10 as
      well as two more mutants (genR8 and genR8.1) resistant to the above antibiotics
      contained amplifications of gene kmr determining resistance of S.kanamyceticus 1
      to kanamycin. The most intensive amplification was detected in the most resistant
      mutant genR8.1.

PMID- 9606501
TI  - [Gas chromatography in express diagnosis of candidiasis and monitoring of
      antifungal therapy efficacy by D-arabinitol and mannose levels in pediatric
      patients].
AB  - Seventy three children (40 blood and 43 liquor specimens) were examined with the
      use of gas chromatography (GC) to detect background concentrations of Candida
      metabolites. The criterium of the children enrollment to the control group was
      the absence of the clinical and laboratory signs of the fungal infection. The
      normal contents of the fungus metabolites were considered to be 0.51 +/- 0.28
      microgram/ml for D-arabinitol and 17.7 +/- 10.4 micrograms/ml for mannose in the
      serum and 7.24 +/- 3.04 micrograms/ml for D-arabinitol and 67.1 +/- 47.4
      micrograms/ml for mannose in the liquor. Fifty four children at the age of 1
      month to 12 years with the signs of the fungal infection requiring systemic
      antifungal therapy were also examined. Prior to the use of antifungal drugs the
      routine microbiological tests and GC detection of the fungus metabolites were
      performed. The fungus was isolated with the cultural method from the blood in 2
      patients (6.3 per cent), from the mucosa in 25 (71.4 per cent) out of 32 patients
      with fungal complications at the background of cytostatic therapy and
      neutropenia, from the liquor in 3 (21.4 per cent) out of 14 patients with
      meningitis and from the urine in 8 (100 per cent) out of 8 patients with urinary
      infection. The GC examination revealed increased levels of the Candida
      metabolites in 96 per cent of the children. A favourable time course of the
      infection at the background of amphotericin B or fluconasol use was recorded by
      the clinical indices which correlated with a reliable decrease of the contents of
      D-arabinitol and mannose to the normal. The use of GC is recommended in express
      diagnosis of candidiasis especially when the results of the cultural tests are
      negative as well as in monitoring of the fungal therapy efficacy.

PMID- 9606502
TI  - [Cephalosporins in the treatment of children with oncohematologic diseases].
AB  - Clinical efficacy of 3rd generation cephalosporins i.e. oral cefpodoxime and
      parenteral ceftriaxone was studied in the treatment of children with
      oncohematologic pathology. Cefpodoxime proved to be efficient in cases of
      moderate infectious complications in regard to the respiratory tracts. The oral
      administration of the drug provided its usage in outpatients. Ceftriaxone had a
      favourable effect in the treatment of children with more severe processes as a
      rule at the background of agranulocytosis and a lower immune response often with
      a tendency to generalization. No side effects of the cephalosporins were
      observed.

PMID- 9606503
TI  - [Ceftibuten (Cedax)--a novel third generation oral cephalosporin in the treatment
      of bacterial infections].

PMID- 9606505
TI  - [Current problems of antibiotic resistance in the treatment of pediatric
      patients].

PMID- 9606504
TI  - [Susceptibility of community-acquired pneumonia pathogens to azithromycin].
AB  - Two hundred and sixty eight microbial strains were tested for their antibiotic
      susceptibility. Azithromycin (sumamed) was shown to have an efficient inhibitory
      action on pneumococci, streptococci and hemophilic bacilli. Doxycycline and
      gentamicin were not sufficiently active against gram-positive cocci, the same as
      trimethoprime/sulfamethoxazole which was equally not sufficiently active against
      hemophilic bacilli. Adequate therapy of bronchopulmonary diseases requires the
      pathogen antibioticograms.

PMID- 9606506
TI  - [Contribution of M.V. Lomonosov Moscow State University Department of
      Microbiology in the field of antibiotics and specialists training].

PMID- 9606508
TI  - [From present day aviation medicine to aviation anthropologic ecology of the
      future].
AB  - Rationale is given to the proposition that aviation medicine including
      psychophysiology and ergonomics is a peculiar kind of aviation anthropoecology as
      a variety of the present-day integrative science of human. This is grounded,
      firstly, on analysis of any scientific finding of aviation medicine in the light
      of two principles of the contemporary occupational medicine, i.e. human health
      and reasonable risk (which is an equivalent of safety) and, secondly, systemic
      study from this angle of all, from molecular to social, levels of the biological
      integration man of flying.

PMID- 9606507
TI  - [Ultraviolet radiation as a risk factor on the Earth and outer space].
AB  - UVR effects on human health are considered. The critical organs for UVR are skin,
      eye, and the immune system. In the skin, UVR can induce erythema, tanning,
      vitamin D photosynthesis, premature aging, and cancer. UVR has a specific
      immunosuppressive effect on the skin secondary to altered lymphoid cells
      function. It results in inhibition of the anti-neoplastic activity and
      suppression of contact hypersensitivity and delayed hypersensitivity to various
      antigens. UV can induce photokeratoconjunctivitis and play an active role in
      etiology of cataracts, corneal and retinal degeneration, pterigium and uveal
      melanoma. Action spectra and biologically effective doses for the effects are
      presented. Measured UV energy spectra naturally occurring at the Earth's surface
      and in space were used to calculate the effective time of UV exposure to produce
      these effects. Data obtained and modulation of the UV effects by other space
      flight factors are discussed. Quantitative analysis of maximum permissible UV
      levels in the production area established in Russia, USA, and the Netherlands was
      performed. As a result, substantive differences in the approaches of these
      countries to setting limits and permissible ranges were stated. Applicability of
      the UV limits to regulation of natural UV exposures is considered.

PMID- 9606510
TI  - [Functional status of respiratory muscles and physical endurance among women
      under prolonged hypokinesia].
AB  - Validity of the hypothesis for the role of the respiratory muscles in
      deterioration of physical work capacity following long-term hypokinesia was
      tested. Experiments were performed with participation of 8 female subjects aged
      from 27 to 36 years in the 120-day head-down bed rest. Physical performance and
      functional status of the respiratory muscles have been determined during
      incremental loading on bicycle ergometer with normal respiration and breathing
      against additional external resistance. Functional deficit of the respiratory
      muscles due to long-term bed rest was shown not to allow adequate ventilation and
      gas exchange at submaximal loads. This resulted in dyspnea, hypoventilation
      induced decrease in oxygen consumption and carbon dioxide release, hypercapnia,
      and lowered threshold of anaerobic metabolism which, in parallel with the
      deconditioning of the cardiovascular system and the skeletal anti-g musculature,
      were responsible for degradation of aerobic physical work capacity.

PMID- 9606509
TI  - [Clinical and physiological evaluation of bone changes among astronauts after
      long-term space flights].
AB  - Results of the joint Russian/US studies of the effect of microgravity on bone
      tissues in 18 cosmonauts on return from 4.5- to 14.5-month long missions are
      presented. Dual-energy x-ray gamma-absorbtiometry (QDR-1000 W, Hologic, USA) was
      used to measure bone mineral density (BMD, g/cm2) and mineral content (BMC, g) in
      the whole body, the scalp including cervical vertebra, arms, ribs, sternal and
      lumbar regions of the spinal column, pelvis and legs. A clearly defined
      dependence of topography of changes upon the position of a skeletal segment in
      the gravity vector was established. The greatest BMD losses have been observed in
      the skeleton of the lower body, i.e. in pelvic bones (-11.99 +/- 1.22%), lumbar
      vertebra (-5.63 +/- 0.817%), and in proximal femur, particularly in the femoral
      neck (-8.17 +/- 1.24%). Bones of the upper skeleton were either unchanged
      (insignificant) or showed a positive trend. Overall changes in bone mass of the
      whole skeleton of male cosmonauts during the period of about 6 months on mission
      made up -1.41 +/- 0.406% and suggest the mean balance of calcium over flight
      equal to -227 +/- 62.8 mg/day. Reasoning is given to qualify these states of
      cosmonauts' bone tissues as local osteopenia. On the literature and results of
      authors' clinical evidence, discussed is availability of the densitometric data
      for predicting risk of trauma. A biological nature of the changes under
      observation is hypothesized.

PMID- 9606511
TI  - [Human cellular immunity and space flights].
AB  - Results of studying cellular immunity of crew members of long-term space
      missions, data of an experiment with extended head-down tilting of human subjects
      (HDT), and data obtained in the course of adapting immunologic test methods for
      the use in microgravity are summarized. Disorders in immunologic reactivity were
      shown to occur under the conditions of space flight. They included decreases in
      both quantitative and functional indices of cellular immunity, and emergence of
      signs of sensibilization to different allergens. The modified tests were
      evaluated by efficacy of determination of the proliferative activity of
      lymphocytes in minimal volumes of capillary blood inside one-piece syringes with
      a medium containing PHA and the Cytodex-1 suspension, evaluation of natural
      cytotoxicity on the level of an effector cell (number of peripheral blood
      lymphocytes capable of producing conjugates with fixed target cells).
      Sensibilization to allergens of normal human microflora was tested in analogs of
      routine hematocrit capillaries used for examination of healthy donors under
      ordinary rest-work regimen. No significant differences between the standard and
      modified tests were revealed. The proposed test modifications are quite simple in
      use and require minimum of equipment.

PMID- 9606512
TI  - [Influence of space flight factors on peripheral red blood cells in humans].
AB  - Investigations of cosmonauts' peripheral red blood prior to and on days 1, 7 and
      14 post long-term MIR-19 and -20 missions dealt with the morphological
      composition of blood, indices of iron exchange, correlation of erythrocyte
      shapes, and the lipid and phospholipid profiles of the erythrocyte membrane. To
      this avail, methods of light electron microscopy, radioimmune analysis, and thin
      layer microscopy were used. Among the unidirectional shifts in the crewmembers of
      these missions were changes in ion exchange indices and the lipid and
      phospholipid profiles of erythrocyte membrane which were indicative of increased
      microviscosity of the lipid layer. Number of erythrocytes and hemoglobin content
      were reduced; transformed erythrocytes were present. It was also discovered that
      the fraction of normal erythrocytes (diskocytes) was partially replaced by
      spherocytes, cnisocytes in flight and typically by echinocytosis post flight. By
      and large, the observed shifts do not have any clinical implications and are most
      likely the blood system reaction to the stress of readaptation to the terrestrial
      conditions.

PMID- 9606513
TI  - [Influence of semantic stress on the motor program structure].
AB  - To approach the applied aspects of support to operator interacting with the
      aerospace technical systems, the authors are working on the problems of
      structuring the motor programs and deformation caused to them by semantic
      stressful agents. Possibility for varying the composition of locomotion programs
      to ensure success of a general motor task had been experimentally demonstrated.
      Data obtained are viewed from the standpoint of revision of the motor image in
      the psychic control system.

PMID- 9606514
TI  - [Informative value of erythrocyte function in the assessment of ionizing
      radiation effect].
AB  - Proposed are new quantitative criteria of the functional state of erythrocytes
      based on automated recording parameters of the acid hemolysis erythrogram.
      Extended analysis of adaptation of the red blood system in rats exposed to
      ionizing radiation (60CO, 1.25 MeV, 0.5, 1.0, and 6.0 Gy) pointed out that the
      normally existing stimulating effect of diuretic products on accumulation of
      juvenile cellular forms was not changed by the dose of 0.5 Gy but ceased after
      exposure to higher doses. A distinct interrelation (r = 0.83 and 0.61 at p <
      0.003, respectively) was revealed between the number of low-resistant
      erythrocytes (EZR) and subsequent (4 to 7 days later) amount of reticulocytes in
      the norm and following exposure to 0.5 Gy of ionizing radiation. After exposure
      to 1.0 Gy and 6.0 Gy r values were below 0.3 at p > 0.2. A "reference cascade" of
      regression equations on the order of Rt = a + b x EZR could be developed for
      individual evaluation of different stages of impairment of one of the normal
      regulatory mechanisms of hemopoiesis in humans systematically exposed to ionizing
      radiation.

PMID- 9606515
TI  - [Analysis of decompression safety during extravehicular activity of astronauts in
      the light of probability theory].
AB  - Objectives of the study were comparative assessment of the risk of decompression
      sickness (DCS) in human subjects during shirt-sleeve simulation of extravehicular
      activity (EVA) following Russian and U.S. protocols, and analysis of causes of
      the difference between real and simulated EVA decompression safety. To this end,
      DCS risk during exposure to a sing-step decompression was estimated with an
      original method. According to the method, DCS incidence is determined by
      distribution of nucleation efficacy index (z) in the worst body tissues and its
      critical values (zm) as a function of initial nitrogen tension in these tissues
      and final ambient pressure post decompression. Gaussian distribution of z values
      was calculated basing on results of the DCS risk evaluation on the U.S. EVA
      protocol in an unsuited chamber test with various pre-breath procedures (Conkin
      et al., 1987). Half-time of nitrogen washout from the worst tissues was presumed
      to be 480 min. Calculated DCS risk during short-sleeve EVA simulation by the
      Russian and U.S. protocols with identical physical loading made up 19.2% and
      23.4%, respectively. Effects of the working spacesuit pressure, spacesuit
      rigidity, metabolic rates during operations in EVA space suit, transcutaneous
      nitrogen exchange in the oxygen atmosphere of space suit, microgravity,
      analgesics, short compression due to spacesuit leak tests on the eye of EVA are
      discussed. Data of the study illustrate and advocate for high decompression
      safety of current Russian and U.S. EVA protocols.

PMID- 9606516
TI  - [Pharmacological treatment of memory disorders caused by hypoxia and cerebral
      ischemia in rats].
AB  - Experiments with white mongrel rats (both females and males) showed that
      nootropic substances, i.e. sodium hydroxybutyrate, pyracetam, oxyracetam,
      aniracetam, centrophinoxine, nooglutyl, mexydol, semax, amide L-pyroglutamyl-D
      alanine, and MK-801, a specific noncontesting antagonist of the NMDA-receptor
      complex, significantly increased survivability of the animals following bilateral
      occlusion of the common carotid arteries. The nootrops prevented, partly or
      completely, mnestic disorders in the experimental rats. In contrast, MK-801
      profoundly aggravated these disorders. Similar results were obtained with a model
      of hypoxic amnesia. Except for N-acetylglycine amide and amide L-pyroglutamyl-D
      alanine, the nootrops fully or to a considerable extent blocked the development
      of mnestic disorders in hypoxic rats. The authors recommend novel nootrops
      (nooglutyl, mexidol, semax and GVS-111) for the pharmacological correction of
      mnestic disorders consequent to hypoxia or cerebral ischemia.

PMID- 9606517
TI  - [Prognostic model of the space station contamination stage].
AB  - Forty two non-metallic materials, 8 human metabolites and a process liquid
      (ethylene glycol) were selected for development of a prognostic model of space
      station contamination by harmful trace admixtures (HTAs). Removal technologies
      made allowance for absorption by atmospheric condensate (AC) and filter
      adsorption. Calculations took in 18 HTAs representative of 8 classes of
      compounds. Simulation modeling allowed to determine HTA migration rates and
      percent ratio (1), calculate concentrations of contaminants in the atmosphere and
      atmospheric condensate (2), and to assess filter efficiency by comparison of
      loads on the filter and a refrigeration/drying set (3). Comparison of empirical
      and measured data permitted conclusions about adequacy of the model and its
      potentiality for predicting ramifications of nominal and contingency situations.

PMID- 9606518
TI  - [Influence of various microbial contents in drinking water on cellular
      composition of lymphoid plaque in the small intestine of the rat].
AB  - Morphological investigations of rats after extended period of drinking water with
      varying amounts of conventionally pathogenic microflora revealed changes in the
      cellular composition of different morphological/functional sections of lymphoid
      plaques in the small intestine which depended on concentrations of
      microorganisms. Comparing with the control, sites of lymphoid node reproduction
      were significantly richer in the relative number of plaques and large lymphocytes
      when water contained 1,000 microbial bodies in 1 cm3. Concentrations of
      microorganisms higher, the parameters tended down to referential levels. Rise in
      water concentrations of microorganisms was associated with a decrease in the
      relative number of small lymphocytes, i.e. main members of the cell in lymphoid
      nodule mantle with the reproduction site, and an increase in the number of
      plasmatic cells and macrophages in the diffuse lymphoid tissue. Lymphoid nodes
      lacking the reproduction sites were observed in the control and in the group of
      animals who drank minimum microbes (100 cells in 1 cm3). These nodules were
      viewed again in the rats who had drunk maximum antigens (1 000,000 cells in 1
      cm3). These changes point to proliferation and differentiation of lymphoid cells
      driven by water microorganisms, and inhibition of these processes by water
      concentrations of conventionally pathogenic microflora above 1,000 microbial
      bodies in 1 cm3.

PMID- 9606519
TI  - [Influence of lactobacterin on the upper respiratory tract microflora of subjects
      with microflora disorders].
AB  - High respiratory tract microflora recovery has been revealed in human subjects
      treated perorally with commercial Lactobacterinum. In most of the participants in
      the study, different (up to epidemically significant) values of disbiotic shifts
      including persistence of conventional pathogens (enterobacteria) and pathogenic
      staphylococci in high respiratory tract mucosa as well as nasopharyngeal
      lactoflora deficiency were observed in the pretreatment period. Significant, in
      the order of one to four, decreases in pathogenic microflora count up to complete
      elimination were accompanied by lactoflora restoration in a part of the subjects
      after treatment. Hence, Lactobacterinum seems to be a perspective means for
      correcting and optimizing the high respiratory tract microflora, especially in
      contingents subjected to the environmental factors with a high risk of disbiotic
      disorders.

PMID- 9606521
TI  - [The development of methodology, means and device for quick detection of aquatic
      bacteria in water supply systems of spacecrafts].
AB  - Microbial contamination is one of the major characteristics of potable water. The
      authors give data illustrating occurrence of various microbial species in the
      inlet products of the water regeneration and supply systems aboard spacecraft.
      Cultural/biochemical techniques of microbial monitoring (TMM) seem to have the
      best outlook for potable water assessment in space flight. To qualify water, TMM
      I (integral indication of micro-organisms), TMM-C (coccal indication), and TMM-BP
      (indication of blue pus Pseudomonas aeroginosa) will be necessary and sufficient.
      Described is a TMM-utilizing unit for microbial analysis.

PMID- 9606520
TI  - [Influence of polyethylene oxide Polyox WSR-301 on the pressure in mesenteric
      arterial microvessels in rats pre-adapted to anti-orthostatic states].
AB  - High-molecular polymers apt to directly influence flow microstructure were tested
      as a fundamentally new method for correcting microhemodynamics in microgravity.
      Pressure in the mesenteric arterial microvessels was measured two weeks in rats
      adapted to the head-down suspension. Intravenous polyethylene oxide (Polyox WSR
      301, end-concentration in the order of 2.10(-7) g/ml), reduced the microvascular
      pressure by 26%, whereas in the control pressure was reduced by only 15%.
      Systemic arterial pressure showed an equal drop in the groups (by 10 to 11%).
      These results suggest that the biomechanical agent weakens resistance to the
      blood flow in the body region where blood supply is impaired by microgravity.

PMID- 9606522
TI  - [Risks of caries as cosmic rays effects during interplanetary space flights].

PMID- 9606523
TI  - Structural neuroimaging and mood disorders: recent findings, implications for
      classification, and future directions.
AB  - Neuroimaging is playing an increasing role in research of affective disorders,
      with investigators examining both volumetric changes of specific brain structures
      and vascular changes within white and gray matter. Recent studies have attempted
      to make clinical correlations between neuroimaging changes in unipolar and
      bipolar mood disorders. In this review, we focus particularly on those changes
      that are clinically meaningful. We conclude that there is enough evidence to
      begin to evaluate inclusion of neuroimaging findings in our mood disorder
      classification system. To this end, we propose two new mood disorder subtypes,
      vascular depression and vascular mania. Directions for future research in
      neuroimaging are then discussed.

PMID- 9606524
TI  - Dopamine and the mechanisms of cognition: Part I. A neural network model
      predicting dopamine effects on selective attention.
AB  - BACKGROUND: Dopamine affects neural information processing, cognition, and
      behavior; however, the mechanisms through which these three levels of function
      are affected have remained unspecified. We present a parallel-distributed
      processing model of dopamine effects on neural ensembles that accounts for
      effects on human performance in a selective attention task. METHODS: Task
      performance is stimulated using principles and mechanisms that capture salient
      aspects of information processing in neural ensembles. Dopamine effects are
      simulated as a change in gain of neural assemblies in the area of release.
      RESULTS: The model leads to different predictions as a function of the
      hypothesized location of dopamine effects. Motor system effects are simulated as
      a change in gain over the response layer of the model. This induces speeding of
      reaction times but an impairment of accuracy. Cognitive attentional effects are
      simulated as a change in gain over the attention layer. This induces a speeding
      of reaction times and an improvement of accuracy, especially at very fast
      reaction times and when processing of the stimulus requires selective attention.
      CONCLUSIONS: A computer simulation using widely accepted principles of processing
      in neural ensembles can account for reaction time distributions and time-accuracy
      curves in a selective attention task. The simulation can be used to generate
      predictions about the effects of dopamine agonists on performance. An empirical
      study evaluating these predictions is described in a companion paper.

PMID- 9606525
TI  - Dopamine and the mechanisms of cognition: Part II. D-amphetamine effects in human
      subjects performing a selective attention task.
AB  - BACKGROUND: A neural network computer model described in a companion paper
      predicted the effects of increased dopamine transmission on selective attention
      under two different hypotheses. METHODS: To evaluate these predictions we
      conducted an empirical study in human subjects of D-amphetamine effects on
      performance of the Eriksen response competition task. Ten healthy volunteers were
      tested before and after placebo or D-amphetamine in a double-blind cross-over
      design. RESULTS: D-amphetamine induced a speeding of reaction time overall and an
      improvement of accuracy at fast reaction times but only in the task condition
      requiring selective attention. CONCLUSIONS: This pattern of results conforms to
      the prediction of the model under the hypothesis that D-amphetamine primarily
      affects dopamine transmission in cognitive rather than motor networks. This
      suggests that the principles embodied in parallel distributed processing models
      of task performance may be sufficient to predict and explain specific behavioral
      effects of some drug actions in the central nervous system.

PMID- 9606526
TI  - Differences in thyroid function between bipolar manic and mixed states.
AB  - BACKGROUND: High rates of thyroid axis abnormalities have been reported in most
      studies of patients with rapid-cycling bipolar disorder. Mixed states share
      similarities with rapid-cycling, including close temporal occurrence of manic and
      depressive symptoms, predominance in women, poor outcome, and less robust
      response to lithium compared with pure mania; however, thyroid axis abnormalities
      have not been well studied in mixed mania. METHODS: To test the hypothesis that
      mixed states are associated with a higher prevalence of hypothyroidism than pure
      mania, immunoreactive triiodothyronine (T3), thyroxine (T4), and thyroid
      stimulating hormone (TSH) concentrations were determined from serum obtained at
      the time of admission in 37 consecutive patients with DSM-III-R bipolar disorder,
      manic or mixed. RESULTS: The mean TSH concentration was significantly higher, and
      the mean T4 concentration was significantly lower in patients with mixed mania
      compared with pure mania. There were no significant differences in T3
      concentration or in previous lithium exposure. CONCLUSIONS: These findings
      suggest thyroid axis dysfunction is more common in bipolar mixed than in bipolar
      manic patients.

PMID- 9606527
TI  - High delta sleep-inducing peptide-like immunoreactivity in plasma in suicidal
      patients with major depressive disorder.
AB  - BACKGROUND: Delta sleep-inducing peptide (DSIP) supposedly involves the
      hypothalamus-pituitary-adrenal (HPA) axis. Previous studies have shown deviated
      plasma DSIP-like immunoreactivity (DSIP-LI) levels, as well as abnormal DSIP-LI
      responses to corticotropin-releasing hormone in patients with major depressive
      disorder (MDD). This study was performed to investigate plasma-DSIP-LI and its
      association with the dexamethasone suppression test (DST) in suicide attempters.
      METHODS: Plasma-DSIP and serum cortisol were measured before and after
      dexamethasone intake in 34 suicide attempters and in healthy age- and sex-matched
      controls. RESULTS: We found significantly elevated DSIP-LI levels in MDD patients
      (p < .005), and a significant correlation between predexamethasone cortisol and
      predexamethasone DSIP-LI levels in healthy controls. Postdexamethasone DSIP-LI
      levels increased in subjects with low predexamethasone DSIP-LI levels, whereas
      they decreased in subjects with high predexamethasone DSIP-LI levels.
      CONCLUSIONS: Results give some support to the theory of glucocorticoid
      involvement in the regulation of DSIP, and suggest altered DSIP-LI levels in
      suicidal MDD patients.

PMID- 9606528
TI  - Platelet serotonin, monoamine oxidase activity, and [3H]paroxetine binding
      related to impulsive suicide attempts and borderline personality disorder.
AB  - BACKGROUND: The aim of the present study was to examine the relationship between
      suicidal behavior and impulsiveness, and more generally borderline personality
      disorder on the one hand, and platelet indicators of central serotonergic
      function on the other. METHODS: After a suicide attempt platelet serotonergic
      measures were obtained from 144 patients with at least one previous attempt. A
      major DSM-III-R Axis I diagnosis and the use of antidepressants were reasons for
      exclusion. RESULTS: Platelet monoamine oxidase (MAO) activity was negatively
      correlated with the personality traits "multi-impulsive behavior" and
      "disinhibition." In accordance, platelet MAO activity was also lower in patients
      with less-planned suicide attempts. Platelet serotonin (5-HT) and recidivism were
      positively correlated with borderline personality disorder, in particular chronic
      feelings of emptiness. Platelet 5-HT was lower in patients with alcohol abuse.
      The maximum number of binding sites (Bmax) for paroxetine binding was positively
      correlated with "sensation seeking." CONCLUSIONS: These findings support the
      hypothesis that serotonergic involvement in impulsive suicidal behavior is
      mediated by the relationship between serotonergic function and impulsiveness as
      personality trait. Other borderline personality traits relevant to recurrent
      suicidal behavior, in particular chronic feelings of emptiness, appear also
      related to serotonergic measures.

PMID- 9606529
TI  - Plasma dexamethasone concentration and cortisol response during manic episodes.
AB  - BACKGROUND: Despite the widespread study of the dexamethasone suppression test
      (DST) in patients diagnosed with major depression, it has been less well studied
      during manic and mixed states of bipolar disorder. METHODS: Cortisol response to
      the administration of 1 mg of dexamethasone was studied in 44 patients diagnosed
      bipolar disorder, manic (n = 37) or mixed (n = 7). Dexamethasone levels and
      cortisol responses were compared between these groups. Four patients initially
      meeting criteria for bipolar disorder, mixed, and 7 patients initially meeting
      criteria for bipolar disorder, manic, all of whom were characterized as DST
      nonsuppressors, were retested after remission. RESULTS: Dexamethasone levels were
      lower and cortisol levels higher in those patients diagnosed bipolar disorder,
      mixed. An inverse correlation was found between log-transformed dexamethasone
      levels and log-transformed cortisol levels at 3 PM (r = -.619, p < or = .001) and
      10 PM (r = -.501, p < or = .001). In those subjects retested after remission,
      dexamethasone levels were higher and cortisol levels lower than during the manic
      and mixed states. CONCLUSIONS: Disturbances in the hypothalamic-pituitary-adrenal
      axis are observed frequently during mixed states of bipolar disorder, but are
      also not uncommon in purely manic episodes. These changes appear to be state
      dependent and revert with treatment.

PMID- 9606530
TI  - Serum levels of thyroid hormones as biological markers in a Swedish forensic
      psychiatric population.
AB  - BACKGROUND: In a Swedish study, delinquent boys had high serum levels of
      triiodothyronine (T3). Furthermore, former delinquents, followed up after about
      30 years, had T3 levels significantly related to repeated criminality. The aim of
      the present study was to shed further light on the relationship between the
      thyroid hormones and specific behaviors and personality characteristics. METHODS:
      Serum levels of T3 and free thyroxine (FT4) were measured in 61 nonpsychotic male
      subjects at forensic psychiatric examinations and 66 normal controls. Psychopathy
      was determined by means of the Psychopathy Checklist-Revised (PCL-R) and DSM-III
      R, DSM-IV, and ICD-10 diagnoses. RESULTS: The study population had high T3 and
      low FT4 values. Elevated T3 levels were related to type II alcoholism, Cluster B
      personality disorders, psychopathy as measured by the PCL-R, criminality, a
      diagnosis of a DSM-IV antisocial disorder, and an ICD-10 dissocial disorder.
      Serum levels of FT4 were negatively related to the same disorders and personality
      traits. CONCLUSIONS: The results indicate an intimate relationship between T3 and
      FT4, and abuse and antisocial behavior. They emphasize the importance of further
      studies on T3 as a biological marker for abuse, social deviance, and repeated
      violent behavior.

PMID- 9606531
TI  - The combined dexamethasone/corticotropin-releasing hormone stimulation test is
      more closely associated with features of diurnal activity of the hypothalamo
      pituitary-adrenocortical system than the dexamethasone suppression test.
AB  - BACKGROUND: The dexamethasone suppression test (DST) is a widely used endocrine
      test in psychiatry, but was reported to not allow reliable inferences with regard
      to the basal activity of the hypothalamo-pituitary-adrenocortical (HPA) system.
      We compared the association of the standard DST and the combined
      dexamethasone/corticotropin-releasing hormone (DEX/CRH) challenge with parameters
      of diurnal cortisol profiles. METHODS: We performed a DEX/CRH challenge and 24
      hour cortisol profiles in 25 depressed patients (mean age: 47.4 +/- 16.0 years)
      and 33 age-matched healthy controls (mean age: 51.4 +/- 19.3 years). RESULTS: A
      path analysis showed cortisol area under the curve (AUC) after CRH (= DEX/CRH
      status) to be dependent upon minimal 24-hour cortisol and evening frequency of
      pulsatile cortisol release. In contrast, postdexamethasone cortisol (= DST
      status) was related to 24-hour mean cortisol. Simple linear regressions supported
      an association of cortisol AUC with several parameters of the diurnal cortisol
      profiles, which was not true for the standard DST. CONCLUSIONS: We conclude that
      the combined DEX/CRH challenge test is more closely associated with the activity
      of the HPA system than the standard DST in healthy and depressed subjects.

PMID- 9606532
TI  - Peripheral benzodiazepine receptor messenger RNA is decreased in lymphocytes of
      generalized anxiety disorder patients.
AB  - BACKGROUND: The aim of this study was to assess whether the decrease of
      peripheral benzodiazepine receptor (pBR) number in peripheral blood mononuclear
      cells (PBMC), previously observed in patients with generalized anxiety disorder,
      is paralleled by changes in the relative content of messenger RNA (mRNA) encoding
      pBR. METHODS: Eight patients with a DSM-III-R diagnosis of generalized anxiety
      disorder were examined before, during, and after 2'-chloro-N-desmethyl-diazepam
      treatment. Eight healthy subjects were analyzed in parallel. The relative content
      of pBR mRNA was determined by reverse-transcriptase-polymerase chain reaction,
      using beta-actin as internal standard. Kinetic binding properties of pBR were
      measured using 3H-PK11195 as a ligand. RESULTS: pBR and pBR mRNA were
      significantly decreased in untreated generalized anxiety disorder patients as
      compared to controls (by 45% and 70%, respectively). Both pBR density and mRNA
      levels returned to control values during treatment or after withdrawal, which
      also coincided with recovery from anxiety. CONCLUSIONS: These results suggest
      that the turnover rate of pBR is reduced in PBMC of generalized anxiety disorder
      patients, and that this change occurs at the transcriptional level.

PMID- 9606533
TI  - Circannual variations in the binding of [3H]lysergic acid diethylamide to
      serotonin2A receptors and of [3H]paroxetine to serotonin uptake sites in
      platelets from healthy volunteers.
AB  - BACKGROUND: Circannual variations occur in several serotonergic parameters,
      including platelet serotonin uptake and platelet [3H]imipramine binding. METHODS:
      Binding of [3H]lysergic acid diethylamide ([3H]LSD) to platelet serotonin (5
      HT)2A receptors and binding of [3H]paroxetine to platelet serotonin uptake sites
      were studied longitudinally for 1 year in 12 healthy volunteers. RESULTS: For
      [3H]LSD, the number of binding sites (Bmax) showed no significant seasonal
      variation (two-way analysis of variance), although Bmax was significantly higher
      during the months October through February than during the months April through
      August (32.6 vs. 29.8 fmol/mg protein; p = .015). For [3H]paroxetine, Bmax showed
      a significant seasonal variation (p = .003) with maximum in August (1322 fmol/mg
      protein) and minimum in February (1168 fmol/mg protein). The affinity constant
      (Kd) showed a significant seasonal variation for [3H]LSD binding (p = .046), but
      not for [3H]paroxetine binding. The seasonal fluctuations in [3H]LSD binding and
      in paroxetine binding tended to be inversely correlated for Bmax (r = -.70; p =
      .08) and were significantly negatively correlated for Kd (r = -.88; p = .009).
      CONCLUSIONS: The present study demonstrates a seasonal effect on platelet
      serotonin uptake site binding and indicates a possible seasonal effect on 5-HT2A
      receptor binding. The results imply that circannual fluctuations should be taken
      into account when these platelet serotonin markers are studied.

PMID- 9606534
TI  - [Recombination mitochondrial transformations in damaged cardiomyocytes].

PMID- 9606535
TI  - [Effects of changes in extracellular pH on the initial tonus of the main artery
      of the rat brain and its response to serotonin].

PMID- 9606536
TI  - [Possible mechanism of disturbances of saccadic eye movements in patients with
      Parkinson disease].

PMID- 9606537
TI  - [Participation of calcium and phosphoinositide systems of the intracellular
      regulation in adaptation of neurons of olfactory cortex slices to hypoxia in
      vitro].

PMID- 9606538
TI  - [Response of bulbar cardiovascular and respiratory neurons to intra-auricular
      laser irradiation].

PMID- 9606539
TI  - [Structure-functional organization of the bone marrow in dynamics of aging of
      AKR/J mice].

PMID- 9606540
TI  - [Characteristics of electrical activity in spinal dorsal horns and sensorimotor
      cortex of rats with pain syndrome of the spinal origin].

PMID- 9606541
TI  - [Prevention of arrhythmia by periodic hypoxia is mediated by activation of mu-
      and delta-opioid receptors].

PMID- 9606542
TI  - [Effect of endothelin-1 infusion on parameters of the cardiovascular system
      during immobilization stress in Lewis and Wistar rats].

PMID- 9606543
TI  - [Effect of hypokinesia on ultrastructure of the rat neocortex].

PMID- 9606544
TI  - [Study of nontraditional neuromediator nitric oxide in paraventricular nuclei of
      the rat hypothalamus in extreme conditions].

PMID- 9606545
TI  - [Initiation of apoptosis in hepatocytes during long-term arterial hypotension and
      postresuscitation period].

PMID- 9606546
TI  - [Restoration with heptapeptide (synthetic taftsin derivative) of cognitive
      functions impaired by antenatal hypoxia].

PMID- 9606548
TI  - [Comparative analysis of antibiotic effects on free radical oxidation in vitro
      and in vivo].

PMID- 9606547
TI  - [Effect of syngeneic and xenogeneic apolipoprotein B-containing lipoproteids on
      the immune response and phagocytosis in mice].

PMID- 9606549
TI  - [Interleukin-2 and staurosporine abolish inhibition of splenocyte nonspecific
      cytotoxicity caused by high doses of phorbol myristate acetate in rats].

PMID- 9606550
TI  - [Effects of semax and ACTH(5-10) on the impulse activity of central neurons].

PMID- 9606551
TI  - [Effect of modulators of energy metabolism on cyclophosphane toxicity for Daphnia
      magna].

PMID- 9606552
TI  - [Effect of dexamethasone on the activity of alkaline proteases and intracellular
      pH of thymocytes].

PMID- 9606553
TI  - [Effect of contrast agents on the activity of acid phosphatase in mouse
      neutrophils].

PMID- 9606554
TI  - [The role of platelet activating factor in regulation of the phagocytic function
      of macrophages from different organs].

PMID- 9606555
TI  - [Inhibiting effect of glycosaminoglycans from human blood granulocytes on the
      colony-forming activity of bone marrow fibroblasts].

PMID- 9606556
TI  - [Markers of bone tissue resorption in skeleton metastasis].

PMID- 9606557
TI  - [Study of characteristics of the antigen structure of different mycobacteria
      (epitope mapping) with monoclonal antibodies].

PMID- 9606558
TI  - [Study of natural and synthetic cytomedins in the nerve tissue culture].

PMID- 9606559
TI  - [Migration of the dominant pacemaker region in the rat sinoatrial node].

PMID- 9606560
TI  - [Clasmatosis of epithelial cells of the stomach and small intestine during laser
      irradiation].

PMID- 9606561
TI  - [Ultrastructural analysis of the interaction of staphylococci with mono- and
      polynuclear phagocytes during nonphlogogenic and phlogogenic response].

PMID- 9606562
TI  - [Nerve fiber regeneration during laser irradiation of the projection of spinal
      cord nerves].

PMID- 9606563
TI  - [Effect of hemoglobin on the development of Pseudomonas aeruginosa infection].

PMID- 9606564
TI  - [Isolation and analysis of lesion-infiltrating lymphocytes in pulmonary
      tuberculosis].

PMID- 9606565
TI  - [Fibronectin as a part of the wound exudate and its importance in wound healing].

PMID- 9606566
TI  - [The method of stimulation of regenerative processes during inflammatory
      destructive periodontal diseases].

PMID- 9606567
TI  - Fat chance.

PMID- 9606568
TI  - Who should perform pediatric cataract surgery?

PMID- 9606569
TI  - Recent advances in the genetics of macular dystrophies.

PMID- 9606570
TI  - Can different types of retinal emboli be reliably differentiated from one
      another? An inter- and intraobserver agreement study.
AB  - OBJECTIVE: To determine whether ophthalmologists can agree on the qualitative
      assessment of visible retinal emboli. DESIGN: Inter- and intraobserver agreement
      study. SETTING: The retina and vitreous subspecialty session at the 1996 Canadian
      Ophthalmological Society meeting. SUBJECTS: A total of 42 observers, of whom 30
      were retinal specialists. OUTCOME MEASURES: The observers viewed 17 fundus
      photographs of 11 patients with embolic acute retinal artery occlusion and
      classified the visible retinal emboli into one of three groups: cholesterol,
      calcific or other. RESULTS: Overall, there was slight agreement for the 17
      observations (mean kappa = 0.063). The kappa statistic for all cases ranged from
      slight to fair agreement. Slight interobserver agreement for the six unique
      photographs was observed (mean kappa = 0.073). Slight intraobserver agreement was
      found for the three photographs that were shown in different orientations (mean
      kappa = 0.041) and for the two photographs shown with differing magnification
      (mean kappa = 0.102). CONCLUSIONS: Overall both intraobserver and interobserver
      agreement on the qualitative assessment of retinal emboli was poor. With only
      slight agreement on the classification of emboli, systemic evaluation of acute
      retinal artery occlusion should not be based on qualitative assessment of retinal
      emboli.

PMID- 9606571
TI  - The natural history of X-linked retinoschisis.
AB  - OBJECTIVE: To evaluate long-term changes in visual acuity, clinical features and
      complications in X-linked retinoschisis, and to analyse recombinant chromosomes
      in affected males, carrier females and unaffected males to further refine the
      retinoschisis gene locus. DESIGN: Longitudinal study. SETTING: Ophthalmology
      department at a university-affiliated hospital in Saskatoon. PATIENTS: A total of
      92 male patients from 6 pedigrees affected with X-linked retinoschisis examined
      between 1962 and 1994. Of the 92, 73 were followed for a mean of 19.78 (standard
      deviation 8.74) years (range 1.5 to 31 years). Blood samples were taken from 91
      affected males, 100 unaffected males and 86 carrier females for DNA analysis.
      OUTCOME MEASURES: Significant visual loss was defined as a doubling or more in
      the visual angle. Clinical comparisons of fundus features were aided by
      stereoscopic fundus photographs. RESULTS: The mean geometric visual acuity was
      20/67 on initial examination and 20/78 on last assessment. Significant loss in
      visual acuity occurred in 18 (21.2%) of 85 eyes of 43 patients during childhood
      or adolescence and in 20 (17.1%) of 117 eyes of 59 patients in the postadolescent
      period. All 183 eyes had changes at the macula. Peripheral schisis was detected
      in 106 eyes (57.9%), with a mean of 1.48 (standard deviation 1.03) involved
      quadrants. Asymmetric disease was detected in 19 patients (20.6%). Vitreal
      hemorrhages occurred in 24 eyes (13.1%), retinal detachments in 10 (5.5%).
      Thirteen eyes (7.1%) of eight patients had a very poor visual outcome (light
      perception or no light perception). A new gene, XLRSI, was identified by means of
      positional cloning. XLRSI is mutated in affected people. CONCLUSIONS: In
      uncomplicated cases of X-linked retinoschisis the visual prognosis is good. There
      is wide variation in clinical features among those affected and in the disease
      over time.

PMID- 9606572
TI  - Correction of intraocular pressure for changes in central corneal thickness
      following photorefractive keratectomy.
AB  - OBJECTIVE: To investigate the relation between measurements of intraocular
      pressure (IOP) and central corneal thickness (CCT) in myopic patients undergoing
      photorefractive keratectomy (PRK). DESIGN: Descriptive study. SETTING: University
      affiliated eye care centre in Ottawa. PATIENTS: A total of 481 consecutive eyes
      of 318 patients with a mean preoperative refractive error of -6.50 dioptres
      treated with excimer PRK between March 1993 and December 1996. OUTCOME MEASURES:
      IOP measured by Goldmann applanation tonometry and CCT before and 3, 6, 12, 18
      and 24 months after surgery. RESULTS: CCT was a significant predictor of IOP only
      before PRK and 6 months after PRK (p < or = 0.05). The relation between IOP and
      CCT suggests corrections for CCT that are not clinically significant (0.81 mm Hg
      [standard error (SE) 0.33 mm Hg] and 1.00 mm Hg [SE 0.38 mm Hg] per 100 microns
      of corneal thinning preoperatively and at 6 months respectively). On average,
      there was a significant decrease in IOP after PRK (0.96 mm Hg and 1.24 mm Hg at
      12 and 24 months respectively) (p < 0.05). There was a significant correlation
      between change in IOP and change in CCT (decrease of 2.1 mm Hg per 100 microns of
      corneal thinning) (p < 0.05). For a given change in CCT, individual changes in
      IOP were variable, with increases or decreases of more than 5 mm Hg in some
      cases. CONCLUSIONS: There are individual differences in IOP changes following
      PRK. Until further data are available we propose that the change in IOP between
      the preoperative visit (or the fellow eye, if healthy or untreated) and the 12
      month visit be used as an individual correction factor to be applied to IOP
      measurements in the operated eye.

PMID- 9606574
TI  - Digital subtraction fluorescein angiography: a new technique for evaluating
      choroidal neovascular membranes.

PMID- 9606573
TI  - Ophthalmic artery occlusion following orbital inflammation: a clinical and
      histopathological study.

PMID- 9606575
TI  - The ethical basis of psychiatric research: conceptual issues and empirical
      findings.
AB  - The study objective was to clarify the ethical basis of psychiatric research by
      outlining conceptual issues and empirical findings related to the ethics of human
      experimentation. A systematic review of scholarly and empirical literature
      covering three decades was performed. The ethics of human research has come to be
      understood in relation to the principles of respect for persons, beneficence,
      justice, and the ideal of informed consent. Subjects who cannot fully participate
      in informed-consent processes are especially vulnerable to exploitation. Current
      dilemmas stem from insufficient attention to the vulnerabilities of mentally ill
      research participants, problems in applying ethical concepts and guidelines to
      psychiatric research, and claims of research misconduct. Empirical studies
      indicate that (1) psychiatric symptoms significantly affect informed consent, (2)
      psychiatric patients may possess certain strengths with respect to research
      involvement, (3) proxy decision-making is problematic, (4) informed consent is
      also difficult to attain with the medically ill and others, (5) patients are
      motivated to participate in research by the hope of personal benefit, (6) ethical
      aspects of research are poorly documented, and (7) institutional review processes
      may not be adequate to protect vulnerable subjects. Psychiatric research can be
      performed ethically, according to standards set throughout the biomedical and
      behavioral sciences, so long as researchers and institutions are respectful of
      special ethical issues in human experimentation and strive to include vulnerable
      study participants fully in research decisions. However, many gaps in the
      empirical literature exist regarding the specific nature and implementation of
      ethics principles in psychiatric research. Efforts to advance both science and
      ethics, including the study of ethical dimensions of human research itself, are
      essential for the future of psychiatry.

PMID- 9606576
TI  - Psychiatric morbidity following motor vehicle accidents: a review of
      methodological issues.
AB  - Motor vehicle accidents (MVAs), even those of a nonserious nature, appear to
      increase the risk of severe psychiatric morbidity in survivors. The present
      review examines the evidence indicating the levels of psychiatric morbidity in
      MVA survivors. Although no consistent profile has emerged, the most commonly
      reported symptoms are depression, anxiety, irritability, driving phobia, anger,
      sleep disturbances, and headache, with rates of posttraumatic stress disorder
      (PTSD) across studies of 0% to 100%. Variability in the type and severity of
      psychiatric outcomes may be due, in part, to methodological inadequacies in many
      studies, particularly the use of biased population samples, inclusion of subjects
      exposed to varied types of accidents, an absence of a clear definition of PTSD, a
      reliance on clinical judgment rather than the use of objective psychometric
      measures, the failure to include ratings of injury severity, and the absence of
      assessments for past exposure to traumatic events or preexisting posttraumatic
      reactions. The most important concern relates to the use of nonrepresentative
      samples, usually patients referred for medicolegal assessment in whom issues of
      compensation are of central importance. Gender and age differences distinguish
      the compensation group from the general population of MVA survivors, who
      therefore may also differ in the vulnerability to posttraumatic morbidity. It is
      argued that more systematic research on unselected subject samples is critical to
      establish epidemiological data on the true nature and extent of psychiatric
      morbidity following MVAs.

PMID- 9606577
TI  - Swedish normative data on personality using the Temperament and Character
      Inventory.
AB  - The Temperament and Character Inventory (TCI) is a self-report personality
      questionnaire based on Cloninger's psychobiological model of personality, which
      accounts for both normal and abnormal variation in the two major components of
      personality, temperament and character. Normative data for the Swedish TCI based
      on a representative Swedish sample of 1,300 adults are presented, and the
      psychometric properties of the questionnaire are discussed. The structure of the
      Swedish version replicates the American version well for the means, distribution
      of scores, and relationships within the between scales and subscales. Further,
      the Swedish inventory had a reliable factor structure and test-retest
      performance. The results of this study confirm the theory of temperament and
      character as a seven-factor model of personality.

PMID- 9606578
TI  - The role of psychiatric comorbidity in the prediction of readmission for
      detoxification.
AB  - In a prospective study over a 28-month period in Iceland using a representative
      sample (N = 351), the association among patients seeking detoxification between
      comorbid psychopathology and (1) number of lifetime admissions, (2) readmissions
      for detoxification, and (3) a "revolving-door" career (i.e., at least four
      admissions within 30 months) was studied. Psychiatric diagnoses were assigned
      using the Diagnostic Interview Schedule (DIS), and the patients were asked about
      prior admissions for detoxification and then evaluated for 28 months for
      readmissions. Patients with no comorbid diagnoses had the fewest lifetime
      admissions. Agoraphobia/panic disorder predicted readmission (odds ratio [OR],
      5.8) for those with less than two prior admissions. For those with more than
      three prior admissions, readmissions were primarily related to polysubstance
      abuse. The development of a revolving-door career was rare (6%) among those with
      less than four prior admissions. Among others (27%), it was primarily predicted
      by polysubstance abuse. Thus, early recognition and treatment of anxiety
      disorders among substance abusers might prevent further readmissions.

PMID- 9606579
TI  - Gender differences in the receipt of aftercare and psychiatric hospitalization
      among adults with severe mental illness.
AB  - Gender differences in receiving aftercare and being hospitalized for persons with
      severe mental illness were examined. For women, unique predictors for receiving
      aftercare were primarily treatment system responsiveness variables. For men,
      unique predictors of aftercare were from all categories and included being
      accompanied to the psychiatric emergency room (PER) by family or friends and
      having previous psychiatric admissions. More recent outpatient treatment and a
      greater number of previous admissions predicted hospitalization for both men and
      women. Receiving less intense aftercare predicted hospitalization for women but
      not men. Unique predictors of hospitalization for men were a higher level of
      education and a psychotic disorder diagnosis.

PMID- 9606580
TI  - Schizotypal Personality Questionnaire and Wisconsin Card Sorting Test in a
      population of DSM-III-R schizophrenic patients and control subjects.
AB  - Phenomenological, biological, genetic, treatment-response, and outcome data
      support a link between schizotypal personality disorder (SPD) and schizophrenia.
      Furthermore, SPD and normal schizotypy also seem connected, although the
      relationship can at times be ambiguous. In this regard, this study was conducted
      to test the hypothesis of a possible association between neurocognitive
      performance evaluated by the Wisconsin Card Sorting Test (WCST) and schizotypal
      personality traits evaluated by the Schizotypal Personality Questionnaire (SPQ)
      in a nonclinical sample and a sample of schizophrenic patients. The main finding
      of the study was that WCST performance was correlated with SPQ (total and
      subscale) scores in the control group; on the contrary, in the patients, the
      relationship between WCST and SPQ scores was weaker. Taken together, our results
      seem to support the hypothesis that different cognitive aspects (i.e., elementary
      WCST subcomponent scores) correlate differentially with some SPQ schizotypal
      traits in a group of nonclinical subjects. This report underlines the relevance
      of studying normal subjects within the brain-behavior paradigm to highlight the
      brain-behavior relationship in the mental illness.

PMID- 9606581
TI  - Recurrent sleep panic, insomnia, and suicidal behavior in patients with panic
      disorder.
AB  - The purpose of this study was to examine the association between recurrent sleep,
      panic, and suicidal behavior in panic disorder. We compared the recurrent sleep
      panickers (N = 33) with other panickers (N = 34). The Schedule for Affective
      Disorders and Schizophrenia (SADS) suicide subscale was used to rate the severity
      of active suicidality. We found that recurrent sleep panickers also had a higher
      percentage of insomnia and comorbid major depression than the others. A
      multivariate analysis demonstrated an association between recurrent sleep panic
      and suicidal tendencies in patients with panic disorder. Although recurrent sleep
      panic alone is not an independent risk factor for suicidal behavior, it may
      modify the severity of illness in patients with panic disorder.

PMID- 9606582
TI  - The status of alexithymia as a risk factor in medically unexplained physical
      symptoms.
AB  - Some decennia ago, the concept of alexithymia was developed from the clinical
      experience of psychosomaticians who at the time were largely working within a
      psychoanalytic frame of reference. Alexithymia can briefly be described as a
      cognitive-affective disturbance characterized by difficulties in differentiating
      one's feelings and expressing them in words. Clinicians who treat patients with
      medically unexplained physical symptoms may often recognize alexithymic features
      in their patients. It is supposed that alexithymia could be a predisposing factor
      for the development or persistence of medically unexplained physical symptoms. In
      this review, the concept of alexithymia as well as paradigmatic shifts in
      psychoanalysis and psychosomatics are discussed to place the concept of
      alexithymia in its epistemiological context. Furthermore, the empirical
      literature on the association between alexithymia and medically unexplained
      physical symptoms is reviewed. The main conclusions are that alexithymia appears
      to be a theoretically important and clinically appealing concept, but that so far
      the empirical evidence that alexithymia predisposes to the development or
      persistence of medically unexplained physical symptoms is imperfect. This is
      mainly because of the cross-sectional design of most studies and is due to other
      methodological shortcomings, such as the lack of allowance for depression and
      anxiety as possible confounding factors. Suggestions for future research are
      made.

PMID- 9606583
TI  - Efficacy of cyproheptadine for nightmares associated with posttraumatic stress
      disorder.
AB  - A retrospective review of the psychiatric records of nine patients with
      posttraumatic stress disorder (PTSD) was conducted to determine the efficacy of
      cyproheptadine in relieving nightmares. The treatment dose was 4 to 12 mg at
      bedtime. The response varied from complete remission to a decrease in the
      intensity and frequency of nightmares.

PMID- 9606584
TI  - Preserved insight in an artist with extrapersonal spatial neglect.
AB  - Several reports of cases of experienced artists showing neglect after a brain
      lesion can be gleaned from the literature. The analysis of their drawings might
      provide better insight into the symptoms of neglect than that of non-artists's
      production. However, most of these reports are anedoctal. We describe in some
      detail the case of neglect of a distinguished artist, the internationally known
      Federico Fellini (FF), whom we followed-up for two months after his right
      parietal stroke. The neuropsychological profile of his neglect syndrome was
      characterized by left visuo-motor neglect which persisted for two months. At
      onset, FF also showed indications of neglect dyslexia as well as some evidence of
      implicit processing of the neglected parts of visual stimuli. However, there was
      no sign of personal and representational neglect, and FF was well aware of his
      motor and attentional deficits. FF's neglect was characterised by several
      dissociations, of which the lack of functional carryover despite intact
      conceptual and semantic insight is the most relevant.

PMID- 9606585
TI  - Subjective memory evaluations in patients with focal frontal, diencephalic, and
      temporal lobe lesion.
AB  - This paper examines subjective memory evaluations and their correlates in
      patients with focal frontal, diencephalic, or temporal lobe lesions. Although all
      patient groups showed significantly lower subjective memory evaluations than
      healthy subjects, the temporal lobe group rated themselves significantly lower
      than the frontal lobe or diencephalic groups despite comparable severity of
      amnesia, implying more severely impaired 'insight' in the latter two groups.
      There was a 'temporal gradient' such that patients rated their memory for 'old'
      (premorbid) items better than their memory for 'new' (recent) or prospective
      items. As in previous studies, subjective memory evaluations were not correlated
      with measures of 'objective' anterograde memory performance, but the present
      study suggests that subjective evaluations are not randomly determined. It seemed
      to be the site of lesion (frontal and/or diencephalic), rather than underlying
      aetiology, which produced a particularly severe loss of 'insight'. Whether the
      earliest remote or autobiographical memories were preserved or not appeared to be
      an important correlate of current subjective memory evaluations, and patients who
      had been memory-disordered for longer were more likely to evaluate their memory
      as poor than those with a more recent onset.

PMID- 9606586
TI  - Automatic influences of memory in Alzheimer's disease.
AB  - Automatic and controlled influences of memory were examined in 12 patients with
      early Alzheimer's disease (AD) and 12 control subjects. The subjects studied a
      list of words and then received three-letter word stems in three different
      retrieval tasks. In an indirect memory task (word-stem completion priming), they
      were asked to produce the first word that came to mind in response to each stem.
      In an inclusion task, they were required to produce a studied word in response to
      each stem, and in an exclusion task they were asked to produce a new, unstudied
      word for each stem. The performance of the subjects with AD was equal in the
      inclusion and exclusion conditions, showing no evidence of controlled
      recollection for the studied words, while their automatic memory as well as
      priming were preserved. The results provide neuropsychological support for the
      distinction between controlled and automatic memory processes.

PMID- 9606587
TI  - A reconceptualisation of apraxia of speech: a synthesis of evidence.
AB  - This paper presents a reconceptualisation of apraxia of speech (AOS) and reviews
      a range of acoustic and articulatory data which have been reported on apraxia of
      speech. Data from both domains, and previous theoretical debate are discussed as
      support for this cognitive-based reconceptualisation.

PMID- 9606588
TI  - Somatosensory stimulation improves imagery disorders in neglect.
AB  - A group of 9 right brain damaged patients with unilateral neglect performed a set
      of tasks involving mental imagery with and without a transcutaneous electrical
      neural stimulation (TENS) to both sides of the neck. Results showed that TENS on
      the left side of the neck produced significant improvements of performances on
      the left side of mental representations of objects (drawing, shape comparison) as
      well as on left side of mental images of space (description of squares). The
      results suggest that the modification induced by TENS may affect the imagery
      systems involved in objects as well as in space representation.

PMID- 9606589
TI  - Effect of acclimatisation to altitude on learning.
AB  - Long-term exposure to high altitude has been reported to impair cognitive
      functions, possibly resulting in an increased risk of mountain accidents. To
      assess the modification of cognitive functions during acclimatisation to
      altitude, 17 climbers were studied at 5350 m a.s.l. by means of a
      neuropsychological learning test. The results clearly show that by extending the
      period spent at elevations above 5350 m to more than 15 days, the response to a
      memory task was significantly enhanced. The improvements resulting from
      acclimatisation were more evident in the organisation of information than in
      information storage. We suggest that inappropriate acclimatisation has a
      detrimental effect on cognitive functions and the resulting impairment may
      particularly affect the more demanding technical tasks.

PMID- 9606590
TI  - Improvement of the motor deficit of neglect patients through vestibular
      stimulation: evidence for a motor neglect component.
AB  - The effect of vestibular stimulation on motor performance has been studied
      comparatively in 2 groups of hemiplegic patients, one including 9 right brain
      damaged patients (RBD) with neglect, the other 9 left brain-damaged patients
      (LBD) without neglect. In the RBD group, a transient but significant improvement
      of motor performance was observed following stimulation, although motor scores
      remained unchanged in two cases. Moreover, a temporary remission of personal
      neglect and anosognosia was obtained in 8 out of 9 patients. In contrast to the
      RBD group, the motor performance of the LBD group was not improved through
      vestibular stimulation, although a moderate improvement of force was noticed in
      one ambidextrous patient who had shown transient signs of neglect at the acute
      stage. These results suggest the participation of a motor neglect component in
      the motor deficit of neglect patients. The motor neglect component may be
      considered as one of the many manifestations of the neglect syndrome and, as
      such, can be improved by the sensory manipulations which presumably restore a
      conscious representation of the left side of space.

PMID- 9606591
TI  - Deficits in the control of the attentional focus in chronic schizophrenics.
AB  - The ability to control the size of the attentional focus and thus to modulate
      processing efficiency was investigated using simple reaction times in central
      vision in 17 chronic schizophrenic patients and 17 normal control subjects. The
      size of the attentional focus was manipulated by varying the size of a central
      box (i.e., a pre-cue), where the imperative stimulus appeared. In accordance with
      previous studies, in normal controls reaction time increased with box size. In
      contrast, in schizophrenic patients reaction time did not depend on box size.
      That is, schizophrenic patients did not show the inverse relation between size of
      the box and speed of processing, which is observed in normal controls. These
      results suggest that a deficit in controlling the size of the attentional focus
      is a basic impairment in chronic schizophrenia. It was also found that
      schizophrenics are more susceptible than controls to paracontrast.

PMID- 9606592
TI  - Presence of very early events preceding self-paced movements in epileptic
      patients. An intracerebral exploration.
AB  - In epileptic patients explored with depth electrodes kept within the brain for
      several days ("chronic conditions") to localize their focus, recordings were
      taken from the less perturbed deep brain areas, before and during the execution
      of self-paced movements. A few deep leads (some of which were located in areas
      which did not display a classical readiness potential) showed that phasic
      paroxystic events very often occurred 2,000 ms and, sometimes, even about 3,000
      ms before the movement (movement-related events, MREs). This finding suggests
      that the preparation of a "voluntary" self-paced movement may begin well before
      the appearance of the readiness potential or, alternatively, that intracerebral
      paroxystic spikes delay the decision making. This type of phasic process may be
      undetectable in scalp recording from normal subjects and only be revealed when
      some brain structures have become hyper-reactive due to the epileptic process.

PMID- 9606593
TI  - The cerebellar contribution to language and sequential functions: evidence from a
      child with cerebellitis.
AB  - We report the case of a 4 years and 2 months old girl, whose development was
      normal before she suffered from severe viral cerebellitis. When she recovered
      from the acute phase, a complete loss of speech was evident, although language
      comprehension was not impaired. Mutism disappeared after about two weeks, giving
      way to the aphonic utterance of a few words. After three months, her speech was
      slow and monotonous, without phonetic disturbances. She could only produce very
      simple and incomplete sentences in both spontaneous and constrained situations
      and she was able to maintain discourse sequentiality only under continuous
      guidance. No deficit in single-word recognition or naming was detected. Her
      sentence reproduction was good, while verbal fluency was very poor when no cue
      was given, but was normal with category cues. Her intelligence was within the
      normal range, but activities requiring programming, particularly those involving
      sequencing, were very defective. The patient's impairment is attributed to the
      failure of the cerebellar-frontal loops to activate strategies involved in
      processing and programming verbal and sequential functions.

PMID- 9606594
TI  - Specificity of face recognition: recognition of exemplars of non-face objects in
      prosopagnosia.
AB  - We investigated whether the recognition deficits of two patients with long
      standing prosopagnosia would also extend to exemplars within visually homogeneous
      object categories other than faces. Categorical object recognition was unimpaired
      in both patients. One patient was impaired in recognizing exemplars within both
      "living" and "nonliving" object categories. In contrast, the other patient
      performed at normal levels in exemplar recognition. These results provide further
      evidence that prosopagnosia does not necessarily reflect a general disorder in
      exemplar recognition, but can be a face-specific deficit.

PMID- 9606595
TI  - Memory for subject performed tasks in patients with Korsakoff syndrome.
AB  - We examined the ability of alcoholic Korsakoff patients to remember verbal and
      action-related information. Eight Korsakoff patients and eight alcoholic control
      subjects learned action phrases in either subject-performed tasks (SPTs) or
      verbal tasks (VTs). Free recall and recognition tests were then administered.
      Despite the severe anterograde amnesia observed in Korsakoff patients for VTs,
      their memory performance for SPTs was similarly facilitated over VTs as was the
      case with alcoholic controls. Domains preserved in this amnesic syndrome may
      account for the benefit seen when using SPTs in Korsakoff patients. The
      therapeutic utilization of action events for memory rehabilitation is discussed.

PMID- 9606596
TI  - Expression of estrogen receptor and maintenance of hormone-responsive phenotype
      in bovine fetal uterine cells.
AB  - Objectives were to establish conditions for preparation, growth, and maintenance
      of a primary culture cell model of fetal uterine cells, and to determine whether
      cells maintained under those conditions would maintain their capacity to respond
      to estrogen stimulation in vitro. Fetal uteri (n = 19) were enzymatically
      dispersed and grown on Type 1 collagen in Dulbecco's modified Eagle's medium
      (DMEM) with 10% fetal bovine serum. Fetal-uterine cells appeared fibroblast-like
      and exhibited positive immunostaining for both vimentin and cytokeratin. Effects
      of gestational age (GA), passage number (p), and hormonal treatment on appearance
      of specific mRNAs were determined by RT-PCR; relative concentrations of products
      determined by densitometry were analyzed as the ratio of target cDNA to the GAPDH
      loading control. Cells expressed mRNAs for estrogen receptor (ER), TGF-beta, EGF
      R, PRL-R, IL-1 alpha, and IL-6. ER mRNA was greater at 185-200 than at 100-110 d
      GA (P < 0.01). All specific mRNAs examined were greater in p5 cells than p2 at
      both 100-110 (P < 0.01) and 185-200 d GA (P < 0.02). There was no effect of
      estradiol on these specific mRNAs in cells from 100-110 d GA; at 185-200 d GA,
      there was an estradiol (1.0 nM) effect both at 6 hr (P < 0.001) and 24 hr (P <
      0.02). Overall, there was an effect of 8-br-cAMP (1 mM; 6 h) on specific mRNAs in
      cells at both 100-110 (P < 0.001) and 185-200 d GA (P < 0.001). In p5 cells from
      Day 185-200 GA, there was increased cell proliferation (P < 0.001) in response to
      estradiol (1 nM; 24 hr). These data suggest that primary fetal uterine cells
      retain their age-specific and hormone-responsive phenotype under these in vitro
      conditions.

PMID- 9606597
TI  - Partial purification and characterization of two non-FSH steroid-modulating
      factors in rat thymic epithelial cell-conditioned medium (TCM).
AB  - Previously, we have reported that unknown factor(s) in rat thymic epithelial cell
      conditioned medium (TCM) stimulates basal and follicle-stimulating hormone (FSH)
      induced steroid hormone production and aromatase enzyme activity in cultured rat
      granulosa cells. Here we report the partial purification and characterization of
      two of these activities. Thymic epithelial cells were prepared from immature
      female rats and used for TCM production. Lyophilized aliquots of TCM were
      reconstituted with distilled water at 25% of the original volume, applied to a
      gel filtration column, and column fractions were tested for their stimulation of
      steroidogenesis in granulosa cells prepared from immature diethylstilbestrol
      treated rats. Two distinct biologically active regions were identified that
      corresponded to apparent molecular weights of approximately 22,000 and less than
      1,000. The < 1 kDa activity ("TCM-1") stimulated (P < 0.01) basal production of
      progestins [progesterone and 20 alpha-hydroxypregn-4-en-4-one (20 alpha-OH
      progesterone)] and estrogen, and also induced dramatic morphological changes on
      the rat granulosa cells. In contrast, the approximately 22 kDa activity ("TCM
      22") stimulated (P < 0.01) only basal progestins, and had no effect (P < 0.05) on
      basal estrogen production or morphology of the cultured rat granulosa cells. In
      the presence of 100 ng/ml FSH, TCM-1 stimulated (P < 0.01) estradiol and
      progesterone production, whereas TCM-22 stimulated (P < 0.01) progesterone, but
      inhibited (P < 0.01) estradiol production. When both activities were assayed
      together, they were synergistic in stimulating (P < 0.01) basal progesterone
      production, but TCM-22 antagonized (P < 0.01) TCM-1-induced estradiol production.
      The biologic and physico-chemical characteristics of TCM-1 and TCM-22 were
      distinct from one another, as well as from FSH. When subjected to C8 reverse
      phase HPLC. TCM-1 retained its characteristic biologic properties and was eluted
      (54% acetonitrile) as A214-absorbing moiety with a peak retention time of 92-93
      minutes. The elution of TCM-22 was not correlated with an identifiable protein
      peak. These results suggest that ovarian steroid production may be modified by
      non-FSH factors produced by thymic epithelial cells although amino acid
      sequencing of TCM-1 was unsuccessful. This highlights a potential role of the
      thymus gland in regulating ovarian function.

PMID- 9606598
TI  - Concentrations of tissue-type plasminogen activator and relaxin in normal and
      induced-cystic follicles of gilts.
AB  - Manipulation of one ovary in prepubertal gilts treated with pregnant mare serum
      gonadotropin (PMSG) and human chorionic gonadotropin (hCG) results in cysts on
      the manipulated ovary and corpora lutea (CL) on the non-manipulated (control)
      ovary. Because tissue-type plasminogen activator (tPA) might play a role in
      follicular rupture and because relaxin might increase tPA production,
      concentrations of tPA and relaxin in manipulated and control follicles were
      measured at different stages of development. Prepubertal gilts were treated with
      1000 IU PMSG followed by 750 IU hCG at 72 hr later. Follicles on one ovary in
      each gilt were manipulated at laparotomy 48 hr after PMSG administration. Gilts
      were ovariectomized at 72, 90, 108, 114, 144, and 216 hr after PMSG.
      Concentrations of tPA and relaxin were determined for follicular fluid from
      follicles dissected free of ovarian stroma and snap frozen in liquid nitrogen and
      media from follicles cultured for 48 hr. Relaxin did not differ between treatment
      groups (manipulated and control) at any time (P > 0.05); whereas, tPA was greater
      in control follicles at 114 hr after PMSG than in manipulated follicles (P <
      0.01). The effect of pyrilamine, a histamine-1 receptor antagonist, on tPA
      concentrations was determined in manipulated and control follicles collected at
      3, 12, 24, 42, and 66 hr after manipulation. Concentrations of tPA were similar
      in control and manipulated follicles for gilts treated with pyrilamine, but again
      control follicles had greater (P < 0.05) tPA concentrations at 114 hr after PMSG.
      Thus, tPA seems to be involved in ovulation, and blockage of ovulation and
      subsequent cyst formation results from inadequate tPA activity in manipulated
      follicles.

PMID- 9606599
TI  - Effect of naloxone on serum luteinizing hormone concentration in anovulatory
      Holstein cows during the early postpartum period.
AB  - This experiment was conducted to investigate the effect of naloxone (NAL), an
      opioid receptor antagonist, on pituitary LH secretion in anovulatory Holstein
      cows during the early postpartum period when cows were expected to be in negative
      net energy balance. Twenty-three cows (11 primiparous) received either saline (n
      = 12) or 1 mg/kg BW NAL i.v. (n = 11) on Day 14 or 15 postpartum. Jugular blood
      samples were collected at 15-min intervals for 2 hr before and 2.5 hr after NAL
      or saline. All cows received 3 ug gonadotropin releasing hormone (GnRH) at 2.5 hr
      post-NAL or -saline and blood collection was continued for 1 hr. Mean serum
      progesterone concentration was 0.33 +/- 0.2 ng/ml. Mean net energy balance for
      all cows was -5.5 +/- 0.6 Mcal/day. Naloxone caused a transient increase (P <
      0.05) in serum LH concentrations in both primi- and multiparous cows within 45
      min after administration. In contrast, serum LH concentrations remained unchanged
      in saline-treated cows. GnRH increased (P < 0.05) LH and there was no effect of
      treatment. These results suggest that modulation of LH secretion, at least in
      part, may be mediated via endogenous opioids in dairy cows before first
      postpartum ovulation.

PMID- 9606600
TI  - Endocrine responses to weaning and changes in post-weaning diet in the young pig.
AB  - The effects of weaning and changing post-weaning diet composition on growth
      patterns and growth-related hormonal profiles were evaluated in neonatal pigs.
      Forty-eight crossbred piglets were assigned to two groups (n = 24/group) based on
      weaning at 2 or 3 wk of age (2W and 3W groups. respectively). At weaning, piglets
      were removed from the sow and placed on a commercial starter ration for the first
      11 d post-weaning (Phase I diet). At Day 12 post-weaning, pigs were placed on a
      growing ration for the remainder of the study (Phase II diet). Body weights and
      blood samples were collected twice weekly from birth until 42 d of age. Serum
      insulin-like growth factor (IGF)-1, IGF-2, and average daily gain (ADG) were
      reduced (P < 0.05) in both groups as a result of weaning, whereas serum growth
      hormone (GH) was elevated (P < 0.05). Earlier weaning resulted in a greater
      reduction in growth rate and serum IGF-2 values (P < 0.05). Mild reductions in
      ADG occurred after the Phase I to II dietary change in both weaning groups (P <
      0.05), but serum IGF-1 decreased only in the 2W group (P < 0.05). Growth hormone
      concentrations tended to increase after the change in post-weaning diets (P =
      0.07 and 0.16 in 2W and 3W, respectively). Serum thyroxine (T4) and
      triiodothyronine (T3) levels were unaltered by weaning but declined in both
      groups after the change in starter diets (P < 0.05). Changes in cortisol
      concentrations were not associated with weaning or the change in post-weaning
      diets. With the exception of serum IGF-1 concentrations, which were elevated in
      the 2W group, growth and endocrine endpoints were equivalent between experimental
      groups at the end of the study (42 d of age). These results indicate that earlier
      weaning and changing solid diets can more severely affect patterns of early
      growth and related hormone secretion, but effective compensatory mechanisms
      restore normal physiological and physical development.

PMID- 9606601
TI  - The prevention of cancer.
AB  - 1. The major causes of cancer are as follows: (a) Smoking: about a third of U.S.
      cancer (90% of lung cancer). (b) Dietary imbalances, e.g., lack of dietary fruits
      and vegetables: The quarter of the population eating the least fruits and
      vegetables has double the cancer rate for most types of cancer compared to the
      quarter eating the most; micronutrients may account for much of the protective
      effect of fruits and vegetables. Excess calories may also contribute to cancer.
      (c) Chronic infections: mostly in developing countries. (d) Hormonal factors
      influenced by life-style. 2. There is no epidemic of cancer, except for lung
      cancer due to smoking. Cancer mortality rates have declined 16% since 1950
      (excluding lung cancer and adjusted for the increased life span of the
      population). 3. Regulatory policy that is focused on traces of synthetic
      chemicals is based on misconceptions about animal cancer tests. Recent research
      contradicts these ideas: (a) Rodent carcinogens are not rare. Half of all
      chemicals tested in standard high-dose animal cancer tests, whether occurring
      naturally or produced synthetically, are "carcinogens." (b) There are high-dose
      effects in these rodent cancer tests that are not relevant to low-dose human
      exposures and which can explain the high proportion of carcinogens. (c) Though
      99.9% of the chemicals humans ingest are natural, the focus of regulatory policy
      is on synthetic chemicals. Over 1000 chemicals have been described in coffee: 27
      have been tested and 19 are rodent carcinogens. Plants that we eat contain
      thousands of natural pesticides which protect plants from insects and other
      predators: 64 have been tested and 35 are rodent carcinogens. 4. There is no
      convincing evidence that synthetic chemical pollutants are important for human
      cancer. Regulations that try to eliminate minuscule levels of synthetic chemicals
      are enormously expensive: EPA estimates that total expenditures on environmental
      regulations cost $140 billion/year. It has been estimated by others that the
      United States spends 100 times more to prevent one hypothetical, highly uncertain
      death from a synthetic chemical than it spends to save a life by medical
      intervention. Attempting to reduce tiny hypothetical risks also has costs; for
      example, if reducing synthetic pesticides makes fruits and vegetables more
      expensive, thereby decreasing consumption, then cancer will be increased. 5.
      Improved health will come from knowledge due to biomedical research and from life
      style changes by individuals. Little money is spent on biomedical research or on
      educating the public about lifestyle hazards, compared to the cost of
      regulations.

PMID- 9606602
TI  - Reactive oxygen-mediated protein oxidation in aging and disease.
AB  - Highly reactive oxygen species that are formed during normal metabolism and under
      conditions of oxidative stress are able to oxidize proteins or convert lipid and
      carbohydrate derivatives to compounds that react with functional groups on
      proteins. Among other changes, these ROS-mediated reactions lead to the formation
      of protein carbonyl derivatives, which serves as a marker of ROS-mediated protein
      damage. On the basis of this marker, it is established that oxidatively damaged
      protein is associated with aging and some diseases. The accumulation of
      oxidatively damaged protein reflects the balance among a myriad of factors that
      govern the rates of ROS generation and the rate at which damaged protein is
      degraded. Peroxynitrite, which is formed under normal physiological conditions,
      is able to oxidize methionine residues in proteins and to nitrate tyrosine
      residues; however, its ability to do so is dependent on the availability of CO2,
      which stimulates the nitration of tyrosine residues but inhibits the oxidation of
      methionine residues. Nitration of tyrosine residues may contribute to
      peroxynitrite toxicity, as nitration precludes the phosphorylation or
      nucleotidylation of tyrosine residues and thereby seriously compromises one of
      the most important mechanisms of cellular regulation and signal transduction.

PMID- 9606603
TI  - alpha-Lipoic acid: a metabolic antioxidant which regulates NF-kappa B signal
      transduction and protects against oxidative injury.
AB  - Although the metabolic role of alpha-lipoic acid has been known for over 40
      years, it is only recently that its effects when supplied exogenously have become
      known. Exogenous alpha-lipoic acid is reduced intracellularly by at least two and
      possibly three enzymes, and through the actions of its reduced form, it
      influences a number of cell process. These include direct radical scavenging,
      recycling of other antioxidants, accelerating GSH synthesis, and modulating
      transcription factor activity, especially that of NF-kappa B (Fig. 12). These
      mechanisms may account for the sometimes dramatic effects of alpha-lipoic acid in
      oxidative stress conditions (e.g., brain ischemia-reperfusion), and point the way
      toward its therapeutic use.

PMID- 9606604
TI  - Adverse effects of superoxide and defenses: studies with Escherichia coli.

PMID- 9606605
TI  - Origin of multiple mutations in human cancers.

PMID- 9606606
TI  - DNA damage by iron and hydrogen peroxide in vitro and in vivo.

PMID- 9606607
TI  - The role of proliferation in the origin of mutations in mammalian cells.

PMID- 9606608
TI  - Cell proliferation and carcinogenesis.

PMID- 9606609
TI  - What do animal cancer tests tell us about human cancer risk?: Overview of
      analyses of the carcinogenic potency database.
AB  - Many important issues in carcinogenesis can be addressed using our Carcinogenic
      Potency Database, which analyzes and standardizes the literature of chronic
      carcinogenicity tests in laboratory animals. This review is an update and
      overview of our analyses during the past 15 years, using the current database
      that includes results of 5152 experiments on 1298 chemicals. We address the
      following: 1. More than half the 1298 chemicals tested in long-term experiments
      have been evaluated as carcinogens. We describe this positivity rate for several
      subsets of the data (including naturally occurring and synthetic chemicals), and
      we hypothesize and important role in the interpretation of results for increased
      cell division due to administration of high doses. 2. Methodological issues in
      the interpretation of animal cancer tests: constraints on the estimation of
      carcinogenic potency and validity problems associated with using the limited data
      from bioassays to estimate human risk, reproducibility of results in
      carcinogenesis bioassays, comparison of lifetable and summary methods of
      analysis, and summarizing carcinogenic potency when multiple experiments on a
      chemical are positive. 3. Positivity is compared in bioassays for two closely
      related species, rats and mice, tested under similar experimental conditions. We
      assess what information such a comparison can provide about interspecies
      extrapolation. 4. Rodent carcinogens induce tumors in 35 different target organs.
      We describe the frequency of chemicals that induce tumors in rats or mice at each
      target site, and we compare target sites of mutagenic and nonmutagenic rodent
      carcinogens. 5. A broad perspective on evaluation of possible cancer hazards from
      rodent carcinogens is given, by ranking 74 human exposures (natural and
      synthetic) on the HERP indes.

PMID- 9606610
TI  - Multiple steps in carcinogenesis, multiple carcinogenic factors, and multiple
      primary tumors: can we develop an appropriate response for cancer prevention?

PMID- 9606611
TI  - Sex steroid hormones and genetic susceptibility to breast and prostate cancer.

PMID- 9606612
TI  - Megatrials of hormonal replacement therapy.
AB  - Despite the fact that estrogen replacement therapy has been demonstrated to be of
      great value to postmenopausal women, many patients are still reluctant to use it.
      This is primarily because of fears that sex hormone therapy increases the risk of
      developing uterine and breast cancer. Because retrospective epidemiological
      studies have failed to clarify the issue for breast cancer, ambitious prospective
      trials have been initiated to determine the role of hormones in the development
      of breast cancer and cardiovascular disease. The main studies have been the
      Women's Health Initiative, the Postmenopausal Estrogen/Progestin Intervention
      (PEPI) Trial, the Heart and Estrogen-Progestin Replacement Study (HERS), the
      Women's International Study of long Duration Oestrogen after Menopause (WISDOM)
      and the Million Women Study. Only the PEPI Trial has been completed. It showed a
      substantial benefit for women using hormone replacement therapy, but was
      insufficiently powerful to determine whether such therapy affected the incidence
      of breast cancer. Despite the immense costs involved and the considerable time
      that must elapse before results are published, it is imperative that these major
      prospective studies are completed, analysed and published. Only then can
      physicians advise their patients in an appropriate manner.

PMID- 9606613
TI  - Urinary incontinence in the elderly. Causes and treatment options.
AB  - Urinary incontinence is a prevalent and distressing condition that affects > 30%
      of elderly individuals. A wide variety of treatment modalities is available, and
      can be effective in reducing or eliminating the symptoms and adverse consequences
      of urinary incontinence. Pharmacological therapy is an important component of the
      successful management of this condition, but the agents currently used do not act
      selectively on the lower urinary tract. Adverse effects of drug treatment are
      common, and are especially problematic in the elderly. A careful assessment of
      the type of urinary incontinence and the institution of a rational management
      programme are the keys to improvement or even cure in patients with this
      condition.

PMID- 9606614
TI  - Optimal treatment of phantom limb pain in the elderly.
AB  - Phantom limb and stump pain is a common sequela of amputation. In geriatric
      patients with an amputated limb and multiple other illnesses, drug therapy may be
      problematic and invasive techniques may be risky. Interactions between
      pathophysiological mechanisms in the peripheral and central nervous systems may
      be responsible for the initiation and maintenance of chronic phantom limb and
      stump pain. These mechanisms include: (i) peripheral damage to nociceptive fibres
      and dorsal root ganglion cells, which acquire abnormal sensitivity to mechanical,
      thermal and chemical stimuli; (ii) the prolonged sensitisation of central
      nociceptive 'second order' neurons in the dorsal horn of the spinal cord, which
      become hyperexcitable and start responding to nonnoxious stimuli; and (iii) the
      degeneration of nociceptive neurons, which may trigger the anatomical sprouting
      of low threshold mechanosensitive terminals to form connections with central
      nociceptive neurons. This may subsequently induce functional synaptic
      reorganisation in the dorsal horn. The provision of a pain-free perioperative
      interval using regional anaesthetic techniques is likely to reduce the incidence
      of phantom limb pain. The therapy of manifest pain is difficult, and treatment
      should start as soon as possible to prevent chronic pain. In the acute state, the
      infusion of calcitonin and oral opioid analgesics have proven to be helpful,
      while established phantom limb pain may respond to antidepressants,
      anticonvulsants and drugs that mimic or enhance gamma-aminobutyric acid function.
      Pharmacological treatment should be combined with transcutaneous electrical nerve
      stimulation, sympathetic blockade and psychotherapy. In addition, new therapeutic
      strategies are now being tested; examples include capsaicin, new anticonvulsants
      and N-methyl-D-aspartate antagonists. Patients with severe pain should be
      referred to a pain specialist to ensure optimal and timely interventional pain
      management.

PMID- 9606616
TI  - Analgesic abuse in the elderly. Renal sequelae and management.
AB  - Nephropathy caused by the use of 'classical' analgesics [paracetamol
      (acetaminophen), salicylates and pyrazolone derivatives] and renal impairment
      associated with nonsteroidal anti-inflammatory drugs (NSAIDs) are important
      health problems in the elderly. Classical analgesic nephropathy is a chronic
      renal disease characterised by renal papillary necrosis and chronic interstitial
      nephritis. The nephropathy is caused by the excessive consumption of analgesic
      mixtures containing at least 2 antipyretic analgesics combined with caffeine
      and/or codeine. The use of NSAIDs is associated with a wide range of tubular,
      interstitial, glomerular and vascular renal lesions. Despite the well
      characterised acute biological effects of NSAIDs on the kidney, there is only
      limited evidence that they are associated with an increased risk of chronic renal
      failure. Classical analgesic toxicity can be effectively prevented by limiting
      the availability of over-the-counter analgesic mixtures containing 2 analgesic
      compounds in combination with potentially addictive substances (e.g. caffeine
      and/or codeine). In the elderly in particular, the prolonged, regular use of
      NSAIDs should be discouraged. Patients starting NSAID therapy should be monitored
      regularly and drug interactions should be avoided.

PMID- 9606615
TI  - Cytokines in rheumatoid arthritis. Potential targets for pharmacological
      intervention.
AB  - The ingress of inflammatory leucocytes into the synovium is a crucial step in the
      pathogenesis of rheumatoid arthritis (RA). Cytokines are mediators involved in
      the inflammatory events, adhesive mechanisms, angiogenesis and osteopenia
      associated with RA. Pro- and anti-inflammatory cytokines, growth factors and
      chemokines all have an important role in these processes. Because the efficacy of
      currently used antirheumatic therapy is often limited, there is a need for more
      specific intervention strategies. Anticytokine therapy may include the use of
      monoclonal antibodies, antagonistic cytokines, soluble cytokine receptors,
      cytokine receptor antagonists, somatic gene transfer or other approaches.
      Hopefully, the study of cytokines and their interactions will lead to the
      development of new immunomodulatory strategies that will benefit patients with
      RA.

PMID- 9606618
TI  - An improved serum free system for cloning human "pure" erythroid colonies. The
      role of different growth factors and cytokines on BFU-E formation by the bone
      marrow and cord blood CD34+ cells.
AB  - We have developed an efficient serum free culture model for cloning human
      erythroid progenitors. Accordingly, human bone marrow or cord blood CD34+ cells
      if plated in our serum free medium and stimulated with a mixture of EpO + KL,
      grow erythroid colonies exclusively. Cells isolated from these cultures express
      glycophorin-A (GPA-A), are CD33-, IIb/IIIa-, and finally all become
      hemoglobinized. By employing this system we also found out that cord blood CD34+
      mononuclear cells (MNC) contain more BFU-E than adult marrow CD34+ MNC, moreover,
      the erythroid colonies formed by cord blood progenitors are significantly larger
      then the ones formed by the marrow cells. We have also compared the influence of
      different cytokines and growth factors, which were reported in the literature to
      costimulate BFU-E growth on cloning efficiency of human BFU-E cultured in our
      serum free medium. We found that from 20 different growth factors and cytokines
      tested, EpO dependent bone marrow BFU-E growth is costimulated only by KL, and to
      lesser degree also by IL-3, GM-CSF, TpO and IL-9. In contrast to marrow cells we
      observed that cord blood BFU-E in addition to KL, IL-3, GM-CSF, TpO, LIF and IL-9
      were also costimulated by NGF-beta, FGF-1, FGF-2 and STK-IL. We found
      simultaneously that TPO which possess only negligible costimulatory effect on
      erythroid colony formation by bone marrow CD34+ cells, significantly costimulated
      the formation of erythroid colonies grown by cord blood CD34+ cells. Therefore,
      the cord blood CD34+ cells are largely committed to erythroid differentiation,
      and, moreover, they respond to a wider spectrum of the growth factors than their
      bone marrow counterparts.

PMID- 9606617
TI  - Bicalutamide in advanced prostate cancer. A review.
AB  - Bicalutamide is a nonsteroidal antiandrogen with a long elimination half-life
      (t1/2) that permits once-daily administration. When combined with a gonadorelin
      (gonadotrophin releasing hormone; GnRH) agonist in maximum androgen blockade
      (MAB) regimens, bicalutamide 50 mg once daily is at least as effective as
      flutamide 250 mg 3 times daily, as shown in a large randomised trial. Rate of
      treatment failure, the primary end-point, was significantly lower at 49 weeks
      with bicalutamide in this study, mainly because of a lower rate of withdrawal due
      to adverse events. Final results at a median follow-up of 160 weeks revealed
      longer median times to progression and death with bicalutamide than flutamide,
      but between-group differences were not significant overall. Although early trials
      demonstrated clinical benefits with bicalutamide 50 mg/day as monotherapy, the
      drug in this dosage is less effective than castration. Increasing the dosage to
      150 mg/day has improved its efficacy in patients with non-metastatic disease:
      combined data from 2 trials demonstrate similar survival with bicalutamide in
      this dosage compared with castration. Accumulating evidence from these and other
      studies indicates that sexual interest appears to be better preserved with
      bicalutamide than with castration. The tolerability profile of bicalutamide is
      characteristic of antiandrogens, with breast pain and gynaecomastia occurring
      most often. Bicalutamide has not been causally associated with problems such as
      interstitial pneumonitis and difficulty with light/dark adaptation seen with
      nilutamide, and in a 50 mg/day dosage causes a lower incidence of diarrhoea than
      flutamide 750 mg/day. Changes in hepatic function are generally transient and
      resolve or improve during therapy or after bicalutamide treatment is withdrawn.
      CONCLUSIONS: Bicalutamide, with its once-daily regimen and good tolerability, is
      an attractive option when combined with a GnRH agonist in patients with advanced
      prostate cancer who are suitable to receive MAB regimens. The role of
      bicalutamide as monotherapy in the management of this common malignancy is
      currently being assessed.

PMID- 9606619
TI  - A novel serum free system for cloning human megakaryocytic progenitors (CFU-Meg).
      The role of thrombopoietin and other cytokines on bone marrow and cord blood CFU
      Meg growth under serum free conditions.
AB  - Human megakaryocytic progenitors (CFU-Megs) are usually cloned in plasma clot
      cultures. Since the medium employed to prepare plasma clot contains animal or
      human serum, there exists a potential risk that CFU-Megs growing in vitro could
      be exposed to the serum derived megakaryopoietic inhibitors. To address this
      issue, we aimed to establish a relatively simple "serum free" cloning model for
      these progenitors. Accordingly, we found that if human bone marrow or cord blood
      CD34+ cells are plated in the methylcellulose medium containing serum substitute,
      and are stimulated with recombinant thrombopoietin (TpO), they exclusively form
      CFU-Meg colonies. Subsequently these colonies can be easily scored with an
      inverted microscope based only on their morphological criteria. We found that the
      cloning efficiency of CFU-Megs was higher in our serum free cloning system than
      in the traditional plasma clot cultures. Since the model proposed in this paper
      is relatively simple, and moreover does not require time consuming immunostaining
      to identify CFU-Meg colonies, it should be widely recommended for studying in
      vitro human megakaryopoiesis. We also found, that under serum free conditions TpO
      is crucial for CFU-Meg formation. In absence of TpO, neither gp 130 activating
      cytokines (IL-6, IL-11, LIF, CNTF) nor the other hematopoietic growth factors or
      cytokines (KL, IL-3, GM-CSF, EpO) were able, when added alone, to stimulate the
      growth of human CFU-Meg colonies. Finally, we report also that cord blood CD34+
      cells are enriched in megakaryocytic progenitors, and moreover, CFU-Megs from
      cord blood possess a higher proliferative capacity than CFU-Megs isolated from
      normal adult bone marrow.

PMID- 9606620
TI  - Electron microscopic localization of acetylcholinesterase activity in the central
      nervous system: chemical basis of a catalytic activity of Hatchett's brown
      (cupric ferrocyanide) precipitate revealed by 3,3'-diaminobenzidine.
AB  - The chemical basis of the histochemical method for acetylcholinesterase described
      by Tago et al. was studied. The primary histochemical reaction of Tago's method
      is performed with diluted Karnovsky's medium, resulting in the in situ formation
      of Karnovsky's precipitate in minute quantities. The visualization of
      acetylcholinesterase activity is made in a secondary reaction where
      diaminobenzidine (DAB) is oxidized in the presence of hydrogen peroxide by the
      peroxidase-like activity of the histochemical precipitate. Since Karnovsky's
      precipitate is already known to be a mixture of Cu+3Fe (CN)6 and Cu++2Fe++(CN)6,
      the catalytic activity of these two complexes was studied in vitro comparatively
      to cupric ferricyanide (non-histochemical precipitate) and to copper and iron
      ions participating in the complexes. We showed that only the first two complexes
      intensely oxidized DAB with or without hydrogen peroxide. Thus, Tago's method is
      based on the same catalytic activity as Hanker's method (oxidation of DAB using
      non-diluted Karnovsky's medium without hydrogen peroxide). Since both complexes
      are able to oxidize DAB without hydrogen peroxide, we propose to describe this
      catalytic activity as oxidoreductase-like activity. Tago's method was modified
      for ultrastructural observations by avoiding metal intensification of the DAB
      precipitate. We obtained fine localization of DAB precipitate in the lumen of
      endoplasmic reticulum and Golgi apparatus of the neurons of substantia nigra.

PMID- 9606621
TI  - Alveolar cells in cyclophosphamide-induced lung injury. The effect of
      pentoxifylline on BAL-isolated cells.
AB  - The present study provides the evaluation of pentoxifylline (PTXF) effect on
      quantitative and morphological changes of cells isolated from the lungs by BAL
      method in animals given cyclophosphamide (CP). CP was administered once,
      intraperitoneally, on the 7th day of the experiment, in a dose of 150 mg/kg b.w.
      PTXF was administered in drinking water in a dose of 30 mg/kg b.w./24 h for 14
      days of the experiment. Morphological examinations of the isolated cells were
      performed using the scanning electron microscope (SEM). An attempt to identify
      type II alveolar epithelial cells was also undertaken. A single CP dose caused a
      significant rise in the total number of cells isolated from the lungs of the
      animals 7 days following CP administration. At the same time, a fall was noted in
      the percentage of neutrophilic granulocytes. No significant quantitative changes
      were observed in the population of cells isolated after 1, 3 and 28 days
      following CP administration. PTXF, in doses applied, did not significantly affect
      quantitative changes and morphological picture of the isolated cells. Our
      observations suggest that none of the methods applied for identification of type
      II pneumocytes are completely specific. At the same time they stain type II cells
      and subpopulations of alveolar macrophages heavily loaded with phagocytized
      surfactant. However, those methods are simple and enable an approximate
      evaluation of damage and regeneration processes in the extracellular alveolar
      lining layer and epithelium.

PMID- 9606622
TI  - The comparison of primordial germ cell populations in embryos of KE and CBA
      inbred strains of mice.
AB  - The changes in primordial germ cell (PGC) populations were compared in embryos of
      two inbred strains of mice-KE and CBA/Kw on 11, 12, 13 and 14 day of foetal life.
      The number of PGCs did not differ in 11-day embryos of both strains. In 12-day
      CBA/Kw embryos the proliferation rate of PGCs was higher and the number of PGC
      was significantly higher than in 12-day KE embryos. However, on subsequent days
      the PGC proliferation rate decreased in CBA/Kw but rapidly increased in KE
      embryos, leading to significantly higher number of PGCs in 14-day KE embryos.
      These differences in proliferation rate between KE and CBA/Kw PGCs can be
      regarded as the reason of strong selection against CBA/Kw derived gametes
      observed in KE<-->CBA aggregation chimaeras.

PMID- 9606623
TI  - Spatial distribution of yolk platelets and fat droplets in oocytes and cleaving
      embryos of the common frog (Rana temporaria) and toad (Bufo bufo).
AB  - Animal-vegetal gradients of fat droplets and yolk platelets have been
      quantitatively determined in mature oocytes and in cleaving embryos in two anuran
      species Rana temporaria and Bufo bufo using stereological methods. Volume
      densities Vv which describe properly the amount of nutrients in embryos have been
      used during the measurements. The embryos till the stage of late blastula are
      spherical: the spherical form is not distorted even by blastocoel forming
      eccentrically, in the animal hemisphere. Increased diameters during cleavage,
      which have been observed in the two species, can be ascribed to growth of the
      blastocoel and increased number of blastomeres while the quantity of the
      cytoplasm does not increase. The volume densities of yolk platelets and fat
      droplets per unit of cytoplasm volume remains constant throughout the cleavage.
      Volume densities change along the animal-vegetal axis in accordance with the
      course of the 3rd polynomial depending on the distance of the area under study
      from the vegetative pole f: y-->Vv, f = ay3 + by2 + cy + d. Parameters of fitting
      functions a, b, c and d change considerably during development of the embryo,
      which proves reorganisation of the cytoplasm during cleavage: the most
      significant changes occur from fertilisation to the four-cell stage and during
      growth of the blastocoel from morula to late blastula stage. Distortion of the
      axial symmetry of yolk platelet distribution in embryos occurring after
      fertilisation is not extensive in the two studied species. The mathematical model
      of spatial distribution of yolk platelets and fat droplets in oocytes and
      cleaving embryos in the studied anuran species was proposed using the above data.

PMID- 9606624
TI  - [Aseptic femur head necrosis--sequelae of systemic corticosteroid therapy?].

PMID- 9606625
TI  - [Evaluation of topical drugs with reference to indications. A selection].
AB  - Between 1988 and 1994 more than 40 monographs dealing with dermatologically
      relevant drugs have been published in an official German government publication,
      the "Bundesanzeiger". These monographs represent reviews compiled by independent
      dermatological and pharmaceutical authorities working together in an expert
      commission and most of their information has proved valid. Thus, knowledge of
      these official reviews could help physicians to decide about the use of many
      drugs. However, they are not well-known to doctors. With this brief summary we
      hope to make more physicians familiar with these important monographs published
      in the "Bundesanzeiger".

PMID- 9606626
TI  - [Inpatient behavioral medicine in chronic skin diseases].
AB  - Behavioral medicine is a newer approach in the management of various diseases. In
      the last years, special programs have been developed for atopic dermatitis,
      psoriasis vulgaris and other chronic skin diseases. An increase in the patient's
      self-control could be achieved by optimizing the patient's skills in dealing with
      their skin disease. The article summarizes the principles and procedures of in
      patient behavioral medicine, especially the strategies employed by dermatological
      training groups and psychotherapeutical groups to help the patient deal with
      their skin disorder.

PMID- 9606627
TI  - [Psychosomatic disorders in dermatology--incidence and need for added
      psychosomatic treatment].
AB  - In a cooperative study involving the Department of Dermatology and the Department
      of Psychosomatic Medicine/Psychotherapy of the University of Dusseldorf, 187
      patients were evaluated for psychosomatic disease and indenient psychological
      testing. The distribution of skin diseases and psychosomatic ICD 10 diagnoses are
      presented. It was found that patient evaluation-(symptom-complaint-questionnaire)
      and expert evaluation correlate positive. It therefore seems worthwhile examining
      dermatology in-patient's for psychosomatic problems in order to facilitate
      combined dermatological and psychosomatic approach not only in the hospital but
      also during the post-discharge ambulatory treatment.

PMID- 9606628
TI  - [Contact eczema in housewives. Update from 1986 with reference to results of
      epicutaneous tests in 2,633 patients].
AB  - The development of hand eczema is a relatively commonly seem dermatosis in
      housewives. In 1986 we presented a first survey of potential contact dermatitis
      sources for a housewife. Now, we present an update in which we analyse the
      different contact sources in the household and grade them in comparison to the
      data of 1986. The results are based on the analysis of a large population of 2633
      patients with the occupation "housewife" and the diagnosis "eczema" who have been
      seen in departments of dermatology belonging to the Information Network of
      Departments of Dermatology (IVDK).

PMID- 9606630
TI  - [Lupus erythematosus/lichen ruber planus overlap syndrome. 5 cases in a patient
      sample of the Erlangen University Dermatology Clinic (1894-1995)].
AB  - The simultaneous occurrence of lupus erythematosus (LE)- and lichen ruber (LP)
      like symptoms is called LE/LP-overlap syndrome (LE/LP-OS). It is defined by
      concomitant clinical, histologic and immunhistologic features of both diseases.
      To date, 47 cases of this rare dermatosis have been reported with marked
      differences in the skin lesions: They are either of intermediate appearance
      between LE and LP (type I = intermediate type), or show a coexistence of LE- and
      LP-specific lesions (type II = polar type). To determine the frequency and
      characteristics of the LE/LP-OS we reviewed our LE-patients from 1984-1995. 5
      cases were diagnosed. The frequency of LE/LP-OS in our patients is higher than
      generally assumed. Due to its variable clinical, histological and
      immunhistological appearance and the lack of unequivocal pathognomonic signs,
      this overlap-dermatosis may be underdiagnosed. Since therapeutic consequences
      result from the diagnosis, criteria are suggested to facilitate the recognition
      of the LE/LP-OS.

PMID- 9606629
TI  - [Mometasone and calcipotriol optimize the initial therapeutic effect of dithranol
      in chronic persistent psoriasis].
AB  - In a randomized study 30 patients with chronic stationary psoriasis were treated
      with 3 different topical schemes. Group 1 (n = 10) received monotherapy
      (dithranol (D) twice a day, D/D), group 2 (n = 10) calcipotriol
      mornings/dithranol evenings (calcipotriol (C)/dithranol (D) C/D) and 3
      (mometasone (M) mornings/dithranol (D) evenings, M/D). During the therapy period
      of 4 weeks we documented the PASI-Score as well as infiltration, erythema and
      desquamation weekly. The M/D group revealed in the first week a significantly
      faster reduction of the PASI-score (5.3) than in the D/D group (PASI 13.22). The
      C/D group (PASI 10.5) show a not significantly faster reduction. After 4 weeks of
      treatment and after a follow period of 6 weeks there were similar PASI-Scores in
      all groups. There were less side-effects in the M/D group than in the others. The
      beginning, more anti-psoriatic effectiveness was achieved by the
      mometasone/dithranol combination than the other schemes. In the long term, the
      effects were similar.

PMID- 9606631
TI  - [Balneophotochemotherapy in disseminated granuloma annulare].
AB  - A 56-year-old female patient with generalized granuloma anulare was treated with
      bath-PUVA therapy with 8-methoxypsoralen. Her diabetes mellitus renal
      insufficiency excluded oral photochemotherapy. A series of 30 treatments resulted
      in complete disappearance of the lesions on the trunk and neck and significant
      improvement of those on the limbs. No side-effects were observed. Bath-PUVA
      therapy seems to have positive effects not only on epidermal, but also on dermal
      processes.

PMID- 9606632
TI  - [Temporary roentgen epilation after embolization of a cerebral arteriovenous
      malformation].
AB  - A patient with a large left-sided arteriovenous malformation underwent
      superselective angiography and therapeutic embolization. Sixteen days later he
      presented with an acute anagen-dystrophic hair loss localized to the occipital
      and right parietal regions corresponding to the irradiated scalp area. The
      diagnosis of an acute radiation injury to the hair follicle from prolonged
      fluoroscopic imaging during the interventional neuroradiologic procedure was
      made. This reversible side effect occurs typically after single short-term
      exposures of 300-400 cGy. Above single doses of 1200 cGy, the epilation is
      permanent. Patients have to be informed about the possibility of this reversible
      complication, which must be distinguished from alopecia areata, postoperative
      ischemic pressure alopecia and drug toxicity.

PMID- 9606633
TI  - [Extensive cutaneous-subcutaneous infiltration as a side-effect of interferon
      beta injection].
AB  - Interferon alpha and gamma have been used to treat several hepatic, hematological
      and oncological diseases for years. Recently, interferon beta has been introduced
      as a therapeutic agent in relapsing-remitting multiple sclerosis. A 41-year-old
      female patient with multiple sclerosis developed non-tender, palm-sized,
      cutaneous-subcutaneous, reddish infiltrates at the injection sites on her thighs
      after 8 weeks of treatment with subcutaneous interferon beta injections.
      Histopathology revealed a perivascular lymphoid infiltrate of the dermis and a
      subtle lobular lymphoid infiltrate of the subcutis. Interferon beta therapy was
      discontinued for 4 weeks. With topical corticosteroids, the skin lesions
      resolved. When subcutaneous injections were resumed at a reduced dose, only
      erythema around injection sites developed without induration or pain. Slight
      erythema and swelling at interferon beta injection site are frequent and rare
      cases of cutaneous necrosis have been described. However, no reports of large,
      painful, cutaneous-subcutaneous infiltrates after interferon beta therapy have
      been published.

PMID- 9606634
TI  - [Seeping gastrointestinal hemorrhage from telangiectasia in CREST syndrome].
AB  - A 55-year-old man with CREST syndrome had marked telangiectasias of the palms,
      the face and the gastrointestinal tract. The latter caused slow bleeding and
      anemia. The telangiectasias were definitely associated with the CREST syndrome.
      Iron substitution was sufficient therapy. If a need for further therapy should
      arise, endoscopic sclerotherapy could be employed. Gastrointestinal bleeding in
      the CREST syndrome is rarely described, probably because it is unrecognized or
      interpreted as hemorrhagic gastritis. The possibility of gastrointestinal
      telangiectasias and concomitant bleeding should be kept in mind in cases of CREST
      syndrome.

PMID- 9606635
TI  - [The Homburg Dermatology Clinic: 50 years University Clinic].
AB  - The dermatological clinic in Homburg was founded in 1945. In 1947 it was
      integrated into the Saarland University as a dermatology department. A review of
      the history of the clinic documents advances and challenges in clinical
      dermatology, as well as new developments in related basic research during the
      last 50 years.

PMID- 9606637
TI  - [20th Annual Meeting of the Society of Operative and Oncological Dermatology.
      Munich 17-19 October 1997].

PMID- 9606636
TI  - [Comment on the contribution by R. Gutzmer, R.A. Herbst, A. Kapp, J. Weiss:
      "SAPHO syndrome"].

PMID- 9606638
TI  - [Topical antibiotics and antiseptics. Agents, spectrum, side effects].

PMID- 9606639
TI  - [Stapes operation in otosclerosis. Considerations on surgical technique and
      choice of prosthesis].

PMID- 9606640
TI  - [Diagnosis of sudden vertigo is still difficult].

PMID- 9606641
TI  - [Data protection in medicine. An example of organization of central registries].

PMID- 9606642
TI  - [Isolated vertigo in vertebrobasilar ischemia--does it exist?].
AB  - An isolated vertigo may occur in vertebrobasilar ischemia, especially as the
      first symptom of cerebellar ischemia or basilar artery occlusive disease. Based
      on neuroanatomical findings, these short-lasting vertigo attacks result from
      transient insufficiency of the anterior inferior cerebellar artery (AICA), which
      supplies the inner ear and leads to ischemia of the upper parts of the vestibular
      labyrinth. Persisting vertigo with or without lateropulsion may occur in
      cerebellar infarctions with involvement of the medial inferior hemispheres due to
      occlusion of the medial branch of the posterior inferior cerebellar artery.
      Caloric testing with oculography can usually differentiate cerebellar infarction
      and peripheral vestibular disease. Since ischemic lesions with AICA insufficiency
      may cause pathological results in caloric testing, both clinical and
      neurophysiological analysis of associated oculomotor signs is essential for a
      correct diagnosis.

PMID- 9606643
TI  - [Use of high sound level in audiometric diagnosis and magnetic resonance
      tomography. Guideline of the German Society of Otorhinolaryngology, Head and Neck
      Surgery].

PMID- 9606644
TI  - [Correlation between myoarthropathies of the masticatory system and ear symptoms
      (otalgia, tinnitus)].
AB  - Speculations concerning a possible association between temporomandibular
      disorders (TMDs) and ear symptoms of otalgia and tinnitus have been made in the
      dental and medical literature for a long time. Current understanding of this
      association is reviewed. An analysis of relevant studies published between 1947
      and 1996 shows that a relatively high percentage of TMD patients reported the
      presence of ear pain and noise. However, a cause-effect relationship has not been
      established to date. Theories that try to explain the concurrence of TMD symptoms
      and ear symptoms (particularly tinnitus) by a common underlying cause remain
      speculative. It has to be taken into consideration that due to their high
      prevalence, TMDs and ear symptoms in a given patients may be present by chance
      alone. A methodological weakness of most of the studies available is the fact
      that control groups were not considered. Owing to the lack of prospective,
      controlled, and randomized studies, statements regarding the effectiveness of
      certain dental measures for the treatment of otalgia and tinnitus in TMD patients
      are not well supported.

PMID- 9606645
TI  - [An osseointegrated micromanipulator as anchor for implantable hearing aid
      transducers. 1: Fitting to the surgical anatomy of the temporal bone and surgical
      technical properties].
AB  - The first electronic implantable hearing aids for patients with hearing loss are
      coupled to the ossicular chain or perilymph during implantation and are now
      available. Our new Tubingen implant designed for sensorineural hearing loss
      (SNHL) is the combination of an implantable microphone and piezotransducer. To
      avoid hearing losses during implantation, the Tubingen piezotransducer will be
      (1) fixed to the mastoid cavity and (2) positioned to one of the ossicular target
      points. This can be done with a micromanipulator which will be implanted together
      with transducer and microphone in the mastoid cavity. The manipulator weights 0.7
      g. With four degrees of freedom, it allows highly secure and safe positioning of
      the transducer's probe tip to the ossicular chain under close to stereotactic
      conditions. The main advantages of the present micromanipulator are (1) easy
      handling during surgery, (2) the transducer's precise positioning to the
      ossicular target point with sufficient degrees of freedom, and (3) the
      transducer's stable fixation in the mastoid cavity in the final position.
      Following integrated safety as the leading principle, ossicular or inner ear
      injuries caused, e.g., by the patient's head movement or unintentional manual
      contact by the surgeon, are minimized. The micromanipulator is, as it were, the
      surgeon's vibration-free "artificial hand". The manipulator's development and its
      optimization to the mastoid cavity by test implantation in 50 human temporal
      bones are shown in detail. While coupling the transducer to the body of the
      incus, transducer, microphone, and micromanipulator can be implanted into 76% of
      all mastoid cavities without protrusion. In the case of transducers coupling to
      the long process of the incus, the protrusion-free implantation rate of the above
      mentioned three implant modules is 78%.

PMID- 9606646
TI  - [Postoperative vestibular compensation and facial nerve function after acoustic
      neuroma operation. Relation to origin of the tumors].
AB  - Within the battery of functional tests used in patients considered to have an
      acoustic neuroma, the use of vestibular examination has been reduced by the
      widespread use of magnetic resonance imaging. Especially small tumors often show
      normal or atypical results in electronystagmographic examinations (ENG). The
      purpose of the present study was to determine the diagnostic value of
      preoperative vestibular diagnosis in predicting the origin of an acoustic
      neuroma, as well as the duration of postoperative vestibular compensation and
      facial nerve function. Sixty-seven patients with intraoperatively confirmed tumor
      origins were examined preoperatively by ENG and electroneurography in addition to
      careful clinical examination. Group 1 (n = 45) consisted of patients with tumor
      originating from the inferior vestibular nerve and group 2 (n = 22) had tumor
      involving the superior vestibular nerve. Postoperatively, facial nerve function
      was determined by using the House grading system and vestibular function was
      defined by ENG 3, 6 and 12 months after surgery. Forty-seven percent of the
      patients in group 1 showed a pathologic caloric response compared to 64% in group
      2. When patients had only a small tumor (< 1 cm), 27% of the patients in group 1
      and 71% in group 2 had abnormal caloric results. Vestibular recovery was
      prolonged in group 1, but a statistically significant difference in postoperative
      facial nerve function could not be found. These findings confirm that especially
      small tumors arising from the inferior vestibular nerve can remain undetected by
      using ENG for diagnosis.

PMID- 9606647
TI  - [Power Doppler and B-mode sonography of nasal mucosa].
AB  - Anatomy and perfusion of the nasal septum and inferior turbinate mucosa can be
      visualized with B-mode and power-Doppler ultrasound. The transducer is placed
      externally on the nasal ala parallel to the pyriform crest and directed towards
      the head of the inferior turbinate of the opposite side. An individually prepared
      dental splint keeps the transducer in position and allows assessment of dynamic
      changes in mucosal swelling and perfusion. Perfusion changes are evaluated by
      computerized quantification of power-Doppler color pixels. Coupling of ultrasound
      across the nasal lumen is achieved by introducing gel into one nasal vestibule
      and flooding the anterior nasal cavity of the side to be visualized with isotonic
      aqueous solutions. Perfusion could be visualized in 23 of 30 subjects, while B
      mode sonographic anatomy was visualized in 16 subjects. The effect of isotonic
      saline solution (10 healthy subjects), naphazoline (10 patients with chronic
      nasal obstruction) and allergen extracts (10 patients with allergic rhinitis) on
      mucosal perfusion and swelling was studied. Isotonic saline solution induced a
      maximum drop in power-Doppler color pixel density by 10% and a maximum increase
      by 27%, but no change was seen in mucosal swelling. Naphazoline induced a 10-57%
      decrease in power-Doppler pixel density and decongestion of the inferior
      turbinate and septum mucosa by 17-43% and 4-27%, respectively. Allergen extracts
      induced an increase in power-Doppler color pixel density by 24-181% and an
      increase in mucosal thickness by 4-31%. These preliminary results encourage
      further studies of nasal mucosal perfusion changes using power-Doppler sonography
      after pharmacologic and allergen provocations.

PMID- 9606648
TI  - [Data protection for the national German Central Registry of Pediatric Hearing
      Disorders].
AB  - The German Registry for Hearing Loss in Children (DZH) processes nationwide data
      from audiological centers. Coping with the accrued data and its subsequent
      management and analysis requires a high degree of security and control. To
      establish a nationwide registry it is necessary at an early stage to take into
      consideration the legal requirements of the participating states. Use of the DZH
      as an example demonstrates how a pragmatic solution can be reached. Special
      issues concerning data collection, transfer, storage and deletion, coding
      strategies to ensure anonymity, checking for duplicate entries, data separation,
      and automated data analysis and data protection are explained.

PMID- 9606649
TI  - [Recurrent meningitis in cleft lip-palate. Sphenopharyngeal meningocele].

PMID- 9606650
TI  - [Objective methods for simulated detection of unilateral deafness with special
      reference to DPOAE (distortion-product otoacoustic emissions) exemplified by a
      case report].
AB  - The simulation of unilateral deafness is very rare. Objective findings are of
      special interest if it happens. A patient with alleged deafness on the left-hand
      side due to commotio cerebri was treated in our hospital. Pure tone audiometry
      showed deafness on the left-hand side and normal hearing on the right-hand side.
      However, stapedius reflexes were found ipsilaterally left as well as
      contralaterally right, at 0.5 to 2 kHz with a stimulation of approximately 90 dB
      SPL. Transiently evoked otoacoustic emissions (TEOAE) and distortion-product
      otoacoustic emissions (DPOAE) were measured. The TEOAE had the same
      reproducibility but a very low response on both sides, such that inner ear
      function could not be evaluated. In comparison, the DP gram showed clear DP
      amplitudes over the whole frequency range on both sides. Nonphysiological DPs
      could be excluded by assessing the DP growth rate at three different frequencies.
      By means of brainstem electric response audiometry (BERA), with which the IV/V
      complex was detectable up to stimulation with 20 dB SPL clicks, and the Stenger
      test, a neural or central hearing loss could be excluded. Normal hearing on the
      left-hand side was thus confirmed. In cases of simulated deafness it is possible
      to prove a normal inner ear function by DPOAE. DPOAE therefore complements the
      list of potential audiological simulation tests.

PMID- 9606651
TI  - [Cervical actinomycosis. A rare differential diagnosis of parotid tumor].
AB  - Actinomycosis is currently an uncommonly diagnosed human disease. However, it can
      still complicate trauma to the respiratory and digestive tracts, including
      operative procedures. A patient with cervicofacial actinomycosis commonly gives a
      history of recent dental manipulation which usually, involves extraction of a
      mandibular molar. The common initial symptoms of infection--such as, sudden onset
      of cervicofacial pain, swelling, erythema, edema and suppuration--can be absent.
      Infection due to actinomyces is a well-known mimic of malignancy is clinical,
      radiological and pathological findings. In the case described a 65-year-old man
      had a mass in his right parotid area. Because of its painless rapid growth with
      infiltration of the mandible as demonstrated by clinical findings and CT and MRI
      scans, we established an initial diagnosis of salivary gland malignancy. Salivary
      gland biopsy then revealed a histological picture of infection due to
      actinomyces. Therapy was initiated with intravenous amoxicillin and sulbactam.
      After 20 days of treatment diseased soft tissues and bone were resected. To
      prevent a relapse the patient received oral clindamycin for 6 weeks. After a
      followup of two years, the patient has remained free of disease.

PMID- 9606652
TI  - [Therapy-dependent cost and reimbursement management. Example of adenoid and
      tumor operations].

PMID- 9606653
TI  - [Therapy refractory fulminant inflammation of the salivary glands. Sialadenitis
      in cytomegalovirus infection].

PMID- 9606654
TI  - [Therapeutic use of botulinum toxin in otorhinolaryngology. 2. Movement disorders
      of craniocervical musculature (except for mimetic musculature) and disorders of
      the autonomic nervous system].

PMID- 9606655
TI  - [Structure and synapses of recurrent collateral axons of motor neurons in the
      vertebrate spinal cord (facts and hypotheses)].
AB  - Original data on structural and functional organization of spinal motoneuron axon
      collaterals in fish, amphibians and reptiles are presented. It is stated for the
      first time that synapses formed by recurrent collaterals on motoneuron dendrites
      should be referred to as excitatory chemical ones according to their
      ultrastructure. Comparison of present findings and reports on motor axon
      collaterals and their synapses in mammals allows to demonstrate characteristic
      features of the structure of neuropil plexus interneurons and synaptic
      connections that determine the action of recurrent inhibition and facilitation
      mechanisms in spinal cord of the vertebrates.

PMID- 9606656
TI  - [The problem of structural modules of the anterior part of the adenohypophysis].
AB  - Insufficiency of analytic approach in examination of the structure of
      adenohypophysis distal part caused the necessity to consider its construction in
      the aspect of living systems. Compartmentalization, polymeria and multilevelness
      as fundamental signs of organ level of the gland organization were demonstrated.
      Markers of different levels compartments and criteria of structural and
      functional units identification were described. Perspectives of the conception of
      the gland module organization are connected with consideration mechanisms of
      hormone production and excretion as well as those of intraorgan structural
      homeostasis:maintenance of integrity, immune surveillance and autoregulation.

PMID- 9606657
TI  - [Cholinergic neurons of the human motor cortex].
AB  - Cytoarchitectonic area 4 of human cerebral cortex was studied by histochemical
      demonstration of choline acetyltransferase (CAT). In layer I CAT reaction
      demonstrated the presence of tangential nerve fibers and synaptic endings on
      Cajal-Retzius neuron. High activity of the enzyme was detected in non-pyramidal
      cell with the axon forming the arcades and establishing contacts on bodies and
      apical dendrites of the layer III pyramidal neurons. Pyramidal neurons were
      divided into cholinergic-non-cholinoceptive, cholinergic-cholinoceptive and non
      cholinergic-cholinoceptive types.

PMID- 9606658
TI  - [Structural asymmetry of cortical areas 44 and 45 in brain of newborns].
AB  - Peculiarities of topography, structure and length of sulci and gyri in left and
      right hemisphere frontal areas were studied in newborns. Peculiarities of
      cytoarchitectonics of speech areas 44 and 45 were described in left and right
      hemisphere of neonatal brain. Differences in the extent of neuron radial
      orientation and thickness of the cortex especially of layer III were defined.
      Great variability in square of areas 44 and 45 in left and right hemisphere of
      neonatal brain was established. A hypothesis on formation of structural asymmetry
      of the Broca center and its areas 44 and 45 by the moment of birth and
      heterochronia of these fields development in ontogenesis is discussed.

PMID- 9606659
TI  - [Histoenzymologic characteristics of cellular elements of the cerebral cortex
      after single physical loads and the action of ozonated isotonic solution].
AB  - Distribution and activities of succinate dehydrogenase and acid phosphatase in
      motor cortex layers I, II, III and VI were studied in 57 outbred male dogs after
      single maximum loads and blood ozonation. Index of physical challenge, running
      velocity of the animal were shown to be potent factors, determining oxidation and
      hydrolysis levels. Dynamics of indexes that characterize these metabolic links
      may serve as an orientation criterion of the adaptive process.

PMID- 9606660
TI  - [Changes in the ultrastructure of the motor zone of the cortex and various areas
      of the rats pyramidal system in acute toxic action of phenazepam].
AB  - As it was revealed by electron microscopic study, phenazepam (benzodiazepine
      representative) administered to rats in acute toxic dose caused astrocyte
      processes swelling mainly in reticular portion of substantia nigra and cerebral
      areas with high density of GABAergic synapses in initial intoxication stage (one
      hour after the drug introduction). Following 24 hrs changes of axodendritic and
      axo-somatic synapse postsynaptic part were detected similar to those of myoneural
      synapses induced by anti-cholinesterase agents, which allows to suggest the
      contribution of the increased intracellular calcium ions content. Specific
      benzodiazepine receptor agonist-flumazenil, introduced 30 min later than
      phenazepam leaded to the decrease of ultrastructural changes in postsynaptic part
      of the synapses in reticular zone of substantia nigra. Thus toxic effect of drugs
      that cause prolonged activity of peripheral and central synapses postsynaptic
      part results in the alike ultrastructural changes irrespective of their mediator
      type and is likely to be connected with the growth of intracellular calcium
      concentration.

PMID- 9606661
TI  - [Localization of the synthesis and transport of phospholipids in myelination in
      the central nervous system].
AB  - The phospholipids constitute a larger percentage of the myelin lipids. In the
      present cytochemical and electronmicroscopic studies we traced the appearance of
      phospholipids in morphological demonstrable form during the different periods of
      myelination in the brain of rabbits (from birth to adulthood). Phospholipids are
      detected in the oligodendrocytes situated along the nerve fibres prior and at
      very beginning of myelination and the neurons during active myelination. After
      completion of myelination no phospholipids could be demonstrated morphologically
      in these cells. The morphological demonstration of phospholipids in the
      oligodendrocytes and neurons during myelination is a manifestation of their
      increased synthesis. We expressed for the first time the view on the existence of
      neuroglial cooperation in the synthesis of myelin phospholipids, subsequently
      confirmed by the studies of axonal lipid transport.

PMID- 9606662
TI  - [Nitroxidergic neurons in the white matter of the human hippocampal formation].
AB  - Distribution of nitric oxide synthase in hippocampal formation of 4 human
      subjects was studied using histochemical NADPH-diaphorase reaction. Two cell
      types (spinous and non-spinous) were distinguished. Type 1 neurons exhibit
      morphological features of pyramidal cells: their apical and basal dendrites are
      thickly covered spines throughout entire length. It is admissible that these
      cells are ectopic pyramidal neurons by their origin and function as acceptors of
      septal and associative and commissural afferents transmitted to hippocampus. Type
      2 cells are morphologically heterogeneous with dipolar, multipolar and round
      neurons present among them. The cells are arranged either one by one or in
      groups, forming synaptic contacts with one another. Adjacent vessels are not only
      accompanied by their long varicose dendrites but are closely surrounded by their
      terminals. Non-spinous hippocampal neurons participate in local blood circulation
      by synthesizing nitric oxide--an endothelium-derived relaxation factor.

PMID- 9606663
TI  - [Comparative cytochemical study of the central nervous system in Wistar and
      August rats in dopamine system hyperfunction].
AB  - Peculiarities of the CNS response to chronic treatment with L-DOPA were revealed
      by quantitative cytochemical methods in August (stress-sensitive) and Wistar
      (emotionally resistant) rats. In August rats L-DOPA administration caused
      aminopeptidase activity increase in sensomotor cortex layer 3 and nucleus
      accumbens, glutamate dehydrogenase activity growth in nucleus accumbens as well
      as the elevation of monoaminoxidase (MAO) activity in nucleus caudatus and
      nucleus accumbens (serotonin as substrate) and in nucleus caudatus and
      hippocampus (tryptamine as substrate), while acetyl cholinesterase activity did
      not change at all. At the same time in Wistar rats only glutamate dehydrogenase
      activity increase was observed in nucleus caudatus and nucleus accumbens.

PMID- 9606664
TI  - [Varying intensity and staining of neurons in the cat visual cortex during
      histochemical detection of horseradish peroxidase].
AB  - We have investigated the staining of different types of neurons after horseradish
      peroxidase injection in the cat striate cortex. The intensity of staining was
      classified as dark, intermediate, or light. Cells with different staining
      intensities were found in all cortical layers and at different distances from the
      injection site. According to the shape of their somata and the organisation of
      their dendritic trees, the labelled cells were identified as pyramidal, small
      pyramidal, non pyramidal and modified pyramidal (inverted and fusiform). The
      ratio of dark:light:intermediate cells within all identified morphological types
      was 2:1:1, except for the modified pyramidal neurons (1:1:1). Revealed
      peculiarity of modified pyramidal cells may serve as additional characteristic of
      this morphological type cells. Thus the intensity of staining depends not only on
      the physical uptake and transportation of enzyme but also on the organisation of
      axonal terminals and neuron location in the functional structure of the cortex.

PMID- 9606665
TI  - [Structural bases of changes in the thermodynamic stability of cerebral cortex
      synapses in albino rats in the postasphyxial period].
AB  - Thermodynamic stability of subsynaptic unit system in cortex molecular layer
      synapses was determined experimentally in albino rats using morphometric methods
      as a value reciprocal to molecular layer cortex relative surface area. Increase
      of number of thermodynamically stable large synapses and their complication was
      found following asphyxia. Synapse reorganization in the course of complication
      results from intensification of counter forces to hypertrophy of subsynaptic unit
      system in large interneuronal contacts.

PMID- 9606666
TI  - [Morphologic manifestations of brain edema during experimental stimulation of the
      hypothalamus].
AB  - By methods of neurohistology, electron microscopy and histochemistry magistral
      and pial arteries of brain, cerebral and cerebellar cortex as well as main
      nuclear structures of midbrain, afterbrain and oblongated marrow were studied in
      39 experimental and 33 control rabbits in dosed effect of electric current
      exerted on hypothalamus through electrodes introduced stereotaxically into
      posterior hypothalamic field. Dynamics of intensity of luminescence and
      distribution density of adrenergic nerve structures in the arteries studied,
      swelling and vacuolization of endotheliocytes in cerebral arterioles and
      capillaries, destruction of mitochondria and lipid drops accumulation in them
      were demonstrated, plasmorrhages and diapedese hemorrhages were noted. Edematous
      changes combined with alterations of oxidation and protein metabolism enzymes
      activity were detected in neurons and gliocytes. A conclusion is made on adequacy
      of the model of experimental hypothalamus stimulation employed in the study in
      order to obtain centrogenic edema for meeting modern goals of neurosurgical
      clinic.

PMID- 9606667
TI  - [Structural and functional organization of sexual dimorphism zones of the
      amygdala in the normal state and in alloxan diabetes].
AB  - Cytoarchitectonics and neuronal organization of sexual dimorphism zones (ZSD) of
      amygdala, one of the brain higher neuroendocrine centres were studied and
      reactive changes of this zone neurons were analysed in rats with chronic alloxan
      diabetes that modulate type I diabetes mellitus in man. Structural organization
      of main ZSD of amygdala--dorsomedial, anterior and basolateral nuclei displays
      its characteristic topographical and cytoarchitectonic peculiarities. Neuronal
      organisation of main amygdala zones is characterized by different ratio of
      intensely and sparsely dendritic long-axonal neurons. Neurons of all ZSD respond
      to insulin deficiency--induced disturbances of carbohydrate metabolism in the
      same type. Reactive changes of neurons defined consist in chromatophilia
      development and neuron shrinkage and also in significant decline in cell nuclear
      volume.

PMID- 9606668
TI  - [Ultrastructural changes in afferent mixed synapses in long-term potentiation of
      electrotonic responses in Mauthner neurons of goldfish medulla oblongata].
AB  - Ultrastructural synaptic features of long-term potentiation (double increase of
      amplitude) of electrotonic responses of the goldfish Mauthner neurons (MN) in
      conditions of prolonged in vitro incubation of medulla oblongata fragments were
      studied. Potentiation was induced by tetanization of the 8th nerve posterior
      roots, axonal terminals of which end on distal segments of MN lateral dendrite as
      piniform mixed synapses and increase their electrotonic conductivity. It was
      established that potentiated synapses vary from control ones in 1) greater length
      of synaptic contact; 20 greater (30% higher) ratio of desmosome like structures
      (DLS); 3) greater area of the DLS individual and total sections (two-fold
      increase); 4) two-fold decrease of total active zone square. Gap junction (GJ)
      parameters did not change. Taking an account of the proven actin origin of DLS,
      reports on actin filaments electron conductivity, close localization of DLS and
      GJ in the synaptic contact and correlative increase of synapse electric
      conductivity and DLS parameters. DLS contribution to electrotonic transmission is
      suggested, direct or mediated by actin interaction with nearby localized GJ
      connexons.

PMID- 9606669
TI  - [The role of polypeptide growth factors and hormones in the formation of
      neuromediator status of a sympathoadrenal cell line].
AB  - Formation of the mixed pattern of neurotransmitter synthesis at intermediate
      stage of neuron functional differentiation involving interaction of nerve and
      epidermal growth factors (NGF and EGF) and also thyroxine was analysed
      histochemically. Analysis of change dynamics of acetyl cholinesterase
      catecholamine ratio influenced by NGF demonstrated its dependence on the cell
      type. Thyroxine potentiates NGF effect while EGF stimulates NGF-induced ACE
      increase only during the initial period.

PMID- 9606670
TI  - [Sympathetic innervation of various endocrine organs in chronic action of lead
      acetate].
AB  - Structure and innervation of paraventricular and supraoptic hypothalamic nuclei,
      thyroid gland, adrenals and ovaries were studied by methods of histochemistry and
      electron microscopy in guinea pigs following chronic treatment with lead acetate
      in doses 50.10 and 0.1 mg/kg per day. A certain dependence between
      sympathoadrenal system activity and morphofunctional parameters of the endocrine
      organs studied was established, which is determined by the pathogenic factor dose
      and duration of effect.

PMID- 9606671
TI  - [Ultrastructure of nerve endings of varying function in the wall of the frog
      urinary bladder].
AB  - Sensory and effector nerve endings were presented at ultrastructural level. Four
      morphological types of receptor terminals were identified that vary in
      peculiarities of neurilemma, organelle composition, matrix structure etc. These
      types were suggested to be ultrastructural equivalents for different functional
      states. Several types of myoneural and neuro-neural synapses and their
      morphological peculiarities were described. The endings explored are a part of
      apparatus of nervous regulation of complicated and variable functions of an organ
      with relatively simple structure.

PMID- 9606672
TI  - Kinetics of the structure of neurites in mollusk brain after its dissociation.
AB  - Using phase microscopy the behaviour of living neurons directly after their
      enzymatic isolation from ganglia of Clione limacina and Lymnaea stagnalis was
      studied. Apart from single-processed unipolar neurons, numerous dipolar and
      unipolar ones were found in mollusc which does not conform to neuron
      classification generally adopted. Disrupted neurons were seen to shorten
      gradually in Ringer solution and -1640 medium at the rate of 0.84-0.27 mm min.
      Serial photomicrography revealed that the process has two stages. Neurite
      retraction is interrupted by the expansion stage (extrusion and urgent
      regeneration). Duration of retraction and extrusion stages made 22.7-3.3 and 6.6
      9.1 min respectively. Retraction speed was 24-0.5 mm/min while that of extrusion
      was 2.8-0.4 mm/min. different processes of the same neuron contract
      asynchronously. Process invagination leads to its rounding. Thus the cell
      acquires most thermodynamically stable from which is arranged to prompt its
      survival. Spherical neurons lacking processes migrate and demonstrate capacity of
      regeneration. As the conditions somehow resembling the experimental ones (high
      proteolytic activity of the medium and process loss in part of neurons) arise in
      cerebral trauma nidus of it is suggested that viable neuron behaviour is alike in
      this situation.

PMID- 9606673
TI  - [Central Asiatic black scorpion venom protect Mauthner neurons from the damaging
      action of prolonged stimulation].
AB  - The effect of long-term natural stimulation resulting in prolonged fatigue and
      structural disorders as well as the black scorpion poison influence on these
      processes were studied in gold fish Mauthner neurons (MN). The poison previously
      applied to MN significantly protects their function and structure from the
      stimulatory effect and subsequently allows the neurons to recover more fast.
      Appearance of numerous desmosome-like (actin-containing) contacts and
      proliferation of subsurface cisterns, the accumulators of calcium ions was noted
      immediately after the poison action and stimulation and one day later in afferent
      synapse ultrastructure. The poison interaction with neuronal actin, mediated by
      alteration of calcium-accumulating systems is probably one of the mechanisms of
      its protective effect.

PMID- 9606674
TI  - [Changes in the neuromediator system of the thymus in rats after splenectomy].
AB  - Removal of spleen leads to compensatory activation of the function of central
      immunogenetic organ and increase of hyperplastic processes in it on d 3
      postoperatively which is accompanied by growth of biogenic amine concentration,
      appearance of bioaminergic areas and lobules-satellites as well as formation of
      new cloe correlative links. Transitory inhibition of immunogenesis occurs on d 15
      and d 30 peaking on d 45 following splenectomy. At this period glycosaminoglycan
      composition of mast cells and their functional activity changes which is
      manifested by appearance of juvenile T-0 forms and new metachromatic types of
      mast cells. In 2 months decrease of APUD cells number and their mono- and diamine
      content and weakening of correlative interconnections is accompanied by true
      significant disturbance in T lymphocytes differentiation, their release in
      peripheral blood and further insufficiency of cellular immunity.

PMID- 9606675
TI  - [The effect of the Karst cave climate on myocardium in experimental pneumonia].
AB  - Chronic pneumonia was modelled on rabbits after Zakharyevskaya-Anichkov method in
      authors own modification. The treatment was performed in the karst cave. Unlike
      to control animals normalization of present alterations in left ventricle
      myocardium was observed in experimental rabbits, regimen and duration of stay in
      the cave being of great importance, e. g. animals kept in the cave
      uninterruptedly for 22 d displayed almost complete normalization of both
      myocardium with its vessels and a series of immunological and biochemical
      parameters.

PMID- 9606676
TI  - [100th anniversary of the birth of the eminent Russian neurohistologist N.G.
      Kolosov].

PMID- 9606677
TI  - [Congestive myelopathy caused by spinal dural arteriovenous fistulas. Anamnesis,
      clinical aspects, diagnosis, therapy and prognosis].
AB  - Congestive myelopathy, formerly referred to as varicosis spinalis or Foix
      Alajouanine syndrome, is caused by a spinal dural arteriovenous fistula (SDAVF).
      So far, the blood supply from the meningeal arteries draining through the fistula
      into the medullary venous system can only be verified by spinal angiography.
      Patients predominantly male and over the age of 60 are afflicted. Initially
      reversible functional disorders caused by the congestion of the spinal cord veins
      eventually become irreversible, the most common symptom being an increasingly
      paretic gait disorder, the signs of which generally begin symmetrically and
      progress from distal to proximal signs. Simultaneously, predominantly transverse
      sensory dysfunctions develop, as well as bladder and bowel dysfunctions, most
      often leading to incontinence. MRI typically shows a central medullary signal
      enhancement with slight swelling of the afflicted region, initially indicative of
      a reversible congestive edema and later of an irreversible infarction, and
      extended perimedullar vessels. Thus, if the clinical course and the
      characteristic MRI findings suggest the possibility of disease related to
      congestive myelopathy, spinal angiography becomes indispensable. Since ensuing
      the success of therapy and prognosis depends on rapid determination of the extent
      of the illness, a speedy diagnostic reaction is mandatory to institute the
      treatment necessary to prevent paraplegia.

PMID- 9606678
TI  - [Therapy of cerebral arteriovenous malformations].
AB  - The rapid development of modern endovascular, microsurgical, and radiation
      therapies has considerably expanded the treatment options for encephalic
      arteriovenous malformations (AVMs). Surgery has the longest history. Single or
      staged intravascular procedures (embolizations) using fast-acting glues,
      sclerotic agents, and thrombogenic coils serve to reduce the size of AVM to that
      suitable for extirpation and may reduce the risk of surgery. Radiation ("gamma
      knife") therapy, most frequently used in small, non-operable AVMs, is also viewed
      by some authors as an alternative or even superior tool in small, operable
      malformations. Partial embolization to reduce the mass-effect of space-occupying
      AVMs, to reverse diaschisis, and to treat AVM-related seizure disorders is being
      discussed and practiced. Given the in part competing or even controversial
      options, the selection of optimal treatment for AVM patients is becoming
      increasingly difficult. Current management is impeded by the paucity of
      information on the exact risks of invasive therapies and by insufficient criteria
      for identifying patients at risk of spontaneous bleeding during the natural
      course, including the seriousness of such hemorrhage.

PMID- 9606679
TI  - [Thoraco-abdominal manifestation of stage II Lyme neuroborreliosis].
AB  - In the past little attention was paid to the thoracoabdominal manifestation of
      Lyme radiculoneuritis, because paralysis of the abdominal wall muscles was
      considered to be a very uncommon clinical manifestation of Lyme neuroborreliosis.
      In a group of 90 patients suffering from early stage Lyme neuroborreliosis we
      found abdominal wall weakness in 11 cases. In the majority of patients
      thoracoabdominal radiculoneuritis was located in the lower thoracic segments (Th
      7-12) and involved more than 3 segments (62%) mostly bilaterally (69%). Abdominal
      wall paralysis was mostly bilateral (91%) and involved always the lower half of
      the abdominal wall. It was very severe in 18%. Electromyographic studies were
      done in the paraspinal and abdominal wall muscles showing fibrillation potentials
      and positive sharp waves in 86% and 50%, respectively. Diagnosis of
      thoracoabdominal radiculoneuritis in Lyme neuroborreliosis may be difficult and
      diagnostic errors may occur. Therefore we recommend to look carefully for
      paralysis of the abdominal wall, which can easily be overlooked on routine
      neurological examination. In patients from an area with a high incidence of Lyme
      disease it is recommended to exclude neuroborreliosis even in patients with known
      diabetes mellitus in order to avoid the misdiagnosis of diabetic thoracoabdominal
      radiculopathy. This has occured in 2 of our patients.

PMID- 9606680
TI  - [Value of functional electrostimulation in patients with paraplegia].
AB  - This 1-year follow-up study included 17 patients with spinal cord injuries who
      participated in a functional electrical stimulation (FES) program for restoration
      of the ability to stand and walk. Four tetraplegic patients reached a mean FES
      assisted standing duration of 6.8 min after 6 weeks. After 1 year three patients
      had stopped FES-assisted standing due to orthostatic problems and only used the
      system for cyclic stimulation of quadriceps muscles while lying down. Ten
      paraplegic patients had a mean standing duration of 22.6 min. The gait velocity
      (gait distance) of seven patients ranged from 2.9 to 24.2 m/min (from 4 to 335 m)
      in seven patients. Due to flexor spasm in two and unrealistic expectations in
      seven cases, four patients stopped the program and five only practiced FES
      assisted standing. One patient continued FES walking after 1 year. Three patients
      with an incomplete cervical lesion who had been able to walk a short distance
      before treatment achieved constant improvement their gait ability. Their gait
      velocity/walking distance without FES improved for a mean of +33.3%/+163.8%,
      after 6 weeks. Assuming that FES is used according to the level of impairment,
      the results favor broader application of the method in the rehabilitation of
      patients with spinal cord injuries.

PMID- 9606681
TI  - [Lumbar spinal stenosis and its surgical treatment].
AB  - Today lumbar spinal stenosis can stand on its own as a clinical entity that can
      be radiologically and clinically divided into central and lateral stenosis.
      Foraminal stenosis is a special form of the latter. During the period 1990-1991
      we operated on 148 patients for spinal stenosis. Using a standardized
      questionnaire, 109 patients were evaluated on their pain and gait status 3 years
      after the operation. Patients with previously known spondylolisthesis or
      degenerative instability were excluded from the study. Forty-four out of 109
      patients were free of pain, while significant reduction of pain was noted in
      35/109 patients. In 19 patients, the pain remained the same or worsened
      postoperatively. Seventy-four out of the 109 patients had no gait disturbances,
      whereas only 14/109 worsened postoperatively. Six patients could walk with
      support and seven patients were unable to walk because of other disturbances.
      Because of unclear responses, the status of the remaining patients could not be
      completely evaluated in either group.

PMID- 9606682
TI  - [Therapeutic strategies in respiratory insufficiency in amyotrophic lateral
      sclerosis. Possibilities and limits].
AB  - In the final stage of amyotrophic lateral sclerosis (ALS) the majority of
      patients develop chronic respiratory failure due to respiratory muscle weakness.
      The interaction between the patient with ALS and the physician should be
      characterized by continuous communication, especially with respect to the
      prospect of ventilatory failure and for support. The patient and his family must
      be informed thoroughly about the natural history and the prognosis of ALS,
      depending on the individual disease process. Already in the early stage of the
      disease coping strategies should be discussed so that imminent respiratory
      emergencies can be handled. If ALS patients are not informed about the acute
      respiratory insufficiency they run the risk of having to be intubated and
      mechanically ventilated over a long term. If dyspnea and hypersecretion dominate
      the final stage of ALS, the therapeutic strategy consists of the administration
      of morphine, insufflation of oxygen and bronchoscopic suction. Mechanical
      ventilation should only be initiated in the exceptional case. However, if dyspnea
      occurs in the early stage of the disease, when there is no bulbar paralysis and
      peripheral muscle function is intact, then noninvasive mechanical ventilation via
      mask may improve the quality of life substantially. Nevertheless, invasive
      mechanical ventilation via a tracheostomy should be avoided.

PMID- 9606683
TI  - [Acute therapy of episodic and chronic cluster headache with sumatriptan s.c.
      Results of a one-year long-term study].
AB  - The aim of the open prospective study was to investigate the efficacy, safety and
      tolerability of subcutaneous sumatriptan in the acute treatment of cluster
      headache. Self-treatment with 6 mg sumatriptan subcutaneously was monitored over
      a period up to 1 year. Headache parameters were documented by the patients with a
      headache diary. A total of 2031 attacks in 52 patients were investigated.
      Treatment with sumatriptan was effective in 88% of the attacks and 57% of the
      patients were pain-free within 15 min after injection; 42% of the patients became
      painfree within 15 min after at least 90% of their attacks. During long-time
      treatment the efficacy remained unchanged. Of the patients 10% withdrew from the
      study due to lack of efficacy or adverse events. In total, 62% of the patients
      reported adverse events, which were serious in 3.8% of the cases. Subcutaneous
      self-treatment of cluster headache is both highly effective and well tolerated.

PMID- 9606684
TI  - [Depressed mood in the acute phase of first ischemic cerebral infarct].
AB  - In the acute phase of cerebral ischemia, 55% of the patients showed signs of mild
      depression after a period of 5-9 days. The development and intensity of
      depressive symptoms correlated strongly with the grade of functional impairment.
      A statistically less significant relationship was established between the
      depressive symptoms and low social status, higher age, lower predisease
      intelligence and accompanying symptoms of anxiety. Independent of antidepressive
      therapy, after 4 weeks an improvement in the initially registered functional and
      intellectual impairment as well as the depressive symptoms (prevalence rate
      23.3%) was recorded. None of these parameters correlated with each other in any
      way. In conclusion, we interpreted these depressive symptoms as the result of
      reactive coping strategies during the acute phase of cerebral ischemia. In
      contrast to this, the aspect of gender showed no significant relationship to the
      resulting depressive symptoms. Furthermore, lesion location, lesion volume, and
      cortical atrophy and cognitive impairment proved to have no influence on
      depressive symptoms. This suggests that primary organic factors are not the cause
      of depression in connection with the acute stroke period.

PMID- 9606685
TI  - [Differential anterior interosseous nerve syndrome diagnosis].
AB  - The differential diagnosis of the rupture of flexor pollicis longus tendon and
      profundus tendon to index finger to the interosseus anterior nerve syndrome can
      be difficult and can lead to misinterpretation of the clinical impression. Two
      cases are reported to demonstrate this problem. In the first case a spontaneous
      rupture of flexor pollicis longus was found, when first an interosseus anterior
      nerve syndrome was suspected. In a second case surgical exploration of flexor
      pollicis longus tendon and profundus tendon to index finger was done on the
      assumption of a rupture, that revealed intact tendons. In a second operation
      neurolysis of the interosseus anterior nerve was carried out with full recovery
      of flexion of the thumb and index finger.

PMID- 9606686
TI  - [Value of magnetic stimulation and F-wave determination in diagnosis of proximal
      demyelinating lesions. Follow-up of acute Guillain-Barre polyradiculitis].
AB  - A 47-year-old woman developed acute Guillain-Barre-syndrome (GBS) within one day,
      presenting tetraparesis (muscle strength 1/5 for the upper and 2/5 for the lower
      extremities) and respiratory failure. On day 5 a cardiac pacemaker was necessary
      due to severe bradycardia. Electrophysiological studies were performed on days 2,
      3, 5, 6, 8, 12, 15, 30 and 40. Our initial findings revealed normal motor
      conduction velocities and normal spinal motor evoked potentials. However, neither
      F-waves nor cortical motor evoked potentials could be registered from the upper
      or lower extremities. The motor conduction of the median nerve remained normal
      until day 6. The compound motor action potential declined thereafter and
      disappeared by day 12, indicating axonal degeneration. No axonal degeneration
      occurred in the lower extremities. The cervical or lumbar magnetic stimulation
      excites nerve roots at the level of the foramen intervertebrale. Thus, our
      findings suggest a conduction block between the foramen intervertebrale and the
      point where the nerve roots enter the spinal cord.

PMID- 9606687
TI  - [Interhemispheric subdural hematoma].
AB  - The interhemispheric subdural hematoma (ISH) is a special subdural hematoma with
      regard to both location and symptomatology. The most widely described clinical
      signs and symptoms associated with an ISH are a lucid interval and the falx
      syndrome. The latter is featured by a contralateral hemiparesis that is
      accentuated in the lower extremity but spares the face. Minor head trauma or a
      preexisting coagulation disorder are also often found. Nonsurgical treatment
      should be chosen in patients with little neurologic dysfunction and a stable
      clinical course. Patients with progressive neurologic deterioration and focal
      neurologic deficits should be operated on without delay. This article provides a
      review of 99 published cases of ISH and adds 3 cases to the existing literature.

PMID- 9606688
TI  - [Septo-optic dysplasia (de Morsier syndrome)].
AB  - Septo-optic dysplasia (or de Morsier syndrome) is a congenital disorder
      characterised by anomalies in cerebral midline structures, optic nerve
      hypoplasia, and hormonal deficiencies. Diagnosis should be made early, due to the
      possibility of treating the hormonal disturbances. We describe here a case with
      decreased visual acuity, one-sided hemianopia, nystagmus und agenesis of the
      septum pellucidum and discuss the heterogeneous appearance of this syndrome.
      There are two theories regarding its pathogenesis. The first postulates
      simultaneous damage to both cerebral structures and optic nerve development
      around the 6th week of gestation, while the other favours secondary degeneration
      of optic nerve fibres due to a cerebral lesion.

PMID- 9606689
TI  - [Differential diagnosis of distal peripheral nerve compression syndrome of the
      tibial nerve. Case report of primitive neuroectodermal tumor].
AB  - Tumors of the tibial nerve are not sufficiently taken into account in the
      diagnosis of tarsal tunnel syndromes (TTS). They may present with atrophy of the
      plantar flectors and with disturbances of sensory functions, but far more
      commonly with pain. Diagnosis is often only achieved after 1-2 years. Taking
      tumors into account when examining patients presenting with TTS may lead to a
      more rapid diagnosis and to improvement in patients' prognoses. We present the
      case of a 37-year-old female in whom a primitive neuroectodermal tumor (PNET) was
      found to be the cause of long-standing pain in the right foot.

PMID- 9606690
TI  - [Intravenous immunoglobulins in therapy of intermittent multiple sclerosis. An
      update].
AB  - Experimental studies and open clinical trials have suggested intravenous
      immunoglobulin (i.v.Ig) as a potentially effective treatment of multiple
      sclerosis (MS). The Austrian Immunoglobulin in Multiple Sclerosis (AIMS) study
      tested this assumption by examining 148 patients with relapsing-remitting MS in a
      randomized, double-blind, placebo controlled fashion (75 i.v.Ig, 73 placebo).
      Monthly administration of i.v.Ig in a dosage of 0.15-0.20 g/kg over a period of 2
      years slowed the progression of or even reversed disability as evident in a total
      of 24% of patients and almost halved the number of relapses in comparison to
      placebo treatment. Therapeutic efficacy was noted within the first 6 months of
      treatment and was not correlated to the severity of disability (mild neurological
      signs without disability to ambulatory with assistance) at study entry. Overall
      the magnitude of treatment effects of i.v.Ig was comparable to that reported for
      beta-interferon and copolymer 1. Further ongoing studies will have to clarify the
      future role of i.v.Ig in the treatment of MS, in particular in the progressive
      forms of the disease.

PMID- 9606691
TI  - Evaluation of 100 Muller curved-stem and 276 Muller long-stem total hip
      arthroplasties after 10 to 15 years of follow-up.
AB  - This study evaluates 376 total hip arthroplasties performed between 1978 and 1983
      using 276 Muller long-stem and 100 Muller curved-stem prostheses. Demographic and
      clinical data were obtained from patient records. All patients still alive who
      did not undergo revision arthroplasty were sent a detailed questionnaire. Results
      indicated that long-term survival of the femoral component of the arthroplasty
      was significantly better when the Muller long-stem was used. Furthermore, there
      was no difference in the clinical out-come between patients who underwent
      revision and those who did not. To eliminate demographic differences between the
      two groups, 77 patients from each group were paired. There was no difference in
      clinical results of the hips between the paired groups, and long-term survival of
      the Muller long-stem was still significantly better using Kaplan-Meier analysis.

PMID- 9606692
TI  - Unreamed rod with early wound closure for grade IIIA and IIIB open tibial
      fractures: analysis of 40 consecutive patients.
AB  - This study evaluated 40 patients with grades IIIA and IIIB open tibial fractures
      from July 1987 to September 1990. Aggressive debridement of all dead tissue and
      bone, irrigation with > 9 L of fluid, and emergent intramedullary unreamed
      rodding (mean time from the emergency room to the operating room: 4 hours 20
      minutes) was performed in all patients. Surgical debridement was repeated every
      48 to 72 hours until the wound could be successfully closed (mean time: 6.2
      days). Progressive weight bearing in a short leg cast was allowed depending on
      the fracture configuration, with full weight bearing usually beginning at 6
      weeks. Additional autogenous iliac crest bone grafting was performed at 2 to 4
      months if required. There were 14 grade IIIA and 26 grade IIIB open tibial
      fractures. Thirty-nine of the 40 patients underwent follow-up until union was
      obtained both clinically and radiographically. One patient was lost to follow-up.
      Complications included three soft-tissue infections and two late subflap
      abscesses. There was no evidence of osteomyelitis in any of these cases.
      Aggressive debridement and early wound closure appear to be the key in the
      successful use of unreamed interlocking intrameduallary rods for fixation of open
      tibial fractures.

PMID- 9606693
TI  - Postoperative epidural analgesia for pediatric spine surgery.
AB  - The safety of epidural infusion for postoperative analgesia in pediatric spine
      surgery continues to be established. A continuous epidural infusion of morphine
      sulfate and bupivacaine was used for postoperative analgesia in 12 pediatric
      patients undergoing spinal surgery. The epidural was placed intraoperatively by
      the operating surgeon, while continuous infusion was managed postoperatively by a
      pediatric anesthesiology pain service team. In addition to the continuous
      infusion, 2 of the 12 also were provided on-demand patient-controlled boluses via
      epidural catheter for breakthrough pain. Patients experienced analgesia as
      documented by a comprehensive pain scale form. No catheters failed, while side
      effects were minimal and easily managed. These results provide confirmation of
      the safety and efficacy of continuous epidural infusion for postoperative
      analgesia following pediatric spine surgery and evidence that patient-controlled
      epidural analgesia is an option.

PMID- 9606694
TI  - Cine magnetic resonance imaging of the subcoracoid region.
AB  - Cine magnetic resonance imaging (MRI) was used to define the normal space between
      the humeral head and coracoid process, known as the subcoracoid space, to
      quantify the subcoracoid space in symptomatic patients and identify the anatomic
      structures responsible for narrowing of this space. The study population was
      comprised of 50 normal volunteers and 75 patients with shoulder pain. All
      subjects underwent cine MRI of the shoulder using a shoulder-rotating device that
      allows progressive rotation of the glenohumeral joint in 10 degrees increments
      from internal to external rotation while scanning the shoulder in the axial
      plane. In asymptomatic patients, the normal interval between the lesser
      tuberosity and coracoid process (coracohumeral distance) averaged 11 mm in
      maximum internal rotation. In symptomatic patients, impingement or entrapment of
      the subscapularis tendon and other soft-tissue structures between the lesser
      tuberosity and the coracoid process in internal rotation was identified, and the
      mean distance between the lesser tuberosity and coracoid process measured 5.5 mm
      in maximum internal rotation. This new MRI technique for shoulder imaging is
      safe, easy to perform, noninvasive, and well-tolerated by patients. Cine MRI
      provides valuable information on the subcoracoid region not obtainable with other
      methods.

PMID- 9606695
TI  - Primary tumors of the elbow: a review of the Leeds Regional Bone Tumour Registry.
AB  - A review of the Leeds Regional Bone Tumour Registry found that primary tumors of
      the elbow constituted 25 (1.2%) of the 2154 cases recorded between 1958 and 1992.
      Fifty percent occurred in the ulna, 20% in the radius, 20% in the humerus, and
      10% in the soft tissues. Benign tumors were more common than malignant ones (19
      versus 6). Malignant tumors occurred more frequently in older patients (mean age:
      45 years) compared with patients with benign tumors (mean age: 17 years). The
      correct preoperative diagnosis was made on clinical or radiologic findings in
      only 16 patients, and the histologic diagnosis of the referring pathologist was
      changed by the Bone Tumour Registry panel in one case. In view of the difficulty
      of accurately diagnosing primary bone tumors, all such lesions should be referred
      to a regional bone tumor registry. Such registries can provide valuable
      information about these uncommon conditions for research, teaching, and
      education.

PMID- 9606696
TI  - Osteogenesis imperfecta: a review of basic science and diagnosis.

PMID- 9606697
TI  - Overview of a general orthopedic practice.
AB  - Records from a 36-year general orthopedic practice were analyzed for patient
      demographics and clinical findings. Results showed that low back pain was the
      most frequent chief complaint and that the majority of the cases were treated
      nonsurgically in the office. A history of trauma was present in 58.8% of cases,
      and job-related injuries were present in 10.6% of cases. The most frequent
      diagnoses are reported for all cases and for some subgroups.

PMID- 9606698
TI  - Diffuse pigmented villonodular synovitis of the knee associated with chronic ACL
      deficiency.

PMID- 9606699
TI  - Cat-scratch disease presenting as an epitrochlear arm mass.

PMID- 9606700
TI  - Rotational acetabular osteotomy in a dysplastic hip with femoral neck
      osteochondromas.

PMID- 9606701
TI  - Multiple familiar occurrence of ochronotic arthropathy.

PMID- 9606702
TI  - Radiologic case study. Transient migratory osteoporosis of the hip and knee.
AB  - Transient migratory osteoporosis is a self-limited disorder characterized by
      gradual onset of pain over several weeks to months and usually accompanied by
      characteristic findings on plain radiographs, scintigraphy, and MRI. Transient
      osteoporosis invariably resolves with conservative management, and therefore it
      is important to distinguish this uncommon syndrome from other disorders such as
      osteonecrosis, osteomyelitis, or infiltrative neoplasms, which require aggressive
      management. An accurate diagnosis of transient bone marrow edema syndrome or
      transient osteoporosis would lead to appropriate conservative management without
      biopsy, as in the case presented here.

PMID- 9606703
TI  - Radiology information systems: evaluation and selection issues.
AB  - This article describes attributes of effective computer systems for radiology
      department management, such as the ability to minimize errors and data entry time
      while maximizing flexibility, data access and productivity. It also discusses
      implementation issues managers should be aware of in evaluating computer systems,
      including hardware platforms, input screens, output options and interfaces with
      other computer systems.

PMID- 9606704
TI  - Cholangiopancreatography using magnetic resonance.
AB  - This article traces the history of efforts to image the biliary tract, focusing
      on magnetic resonance cholangiopancreatography (MRCP). It examines key factors in
      successful MRCP, including coil selection, respiration control, pulse sequences,
      slice mode acquisition and post-processing. The article also presents
      pathological findings of MRCP and discusses the advantages and disadvantages of
      the procedure.

PMID- 9606705
TI  - Medical imaging of facial and mandibular fractures.
AB  - Radiographic imaging is an important tool in the assessment of facial trauma and
      the detection of underlying fractures or other injuries. To achieve the best
      possible cosmetic result, diagnosis and treatment of facial injuries must be
      accurate, thorough and prompt. This article reviews facial anatomy and discusses
      several types of mandible and facial fractures and their causes. It also reviews
      the diagnostic imaging techniques used to evaluate facial fractures, including a
      discussion of the most common views.

PMID- 9606706
TI  - The radiologic technologist's role in patient education.
AB  - This article examines the changing nature of patient education and the reasons
      why radiologic technologists must take a role in educating patients. The elements
      of teaching and effective communication are discussed, along with barriers to
      learning and ways to assess patients' readiness to learn. The article concludes
      with teaching examples drawn from mammography, magnetic resonance imaging,
      angiography and radiography.

PMID- 9606707
TI  - Lasers bring new light to breast imaging.

PMID- 9606708
TI  - Portable radiography.

PMID- 9606709
TI  - Portfolios link education with practice.

PMID- 9606710
TI  - A novel and efficient method for the stable expression of heteromeric ion
      channels in mammalian cells.
AB  - The 5' untranslated leader sequence from the encephalomyocarditis virus was used
      to engineer bicistronic or tricistronic expression vectors encoding two subunits
      (P2X2 and P2X3) of an ATP-gated cation channel. Human embryonic kidney (293) and
      chinese hamster ovary (CHO-K1) cells were transfected with the vector, and stable
      cell lines were generated by single cell subcloning. Selection was made in a 96
      well format on the basis of a sustained increase in intracellular calcium
      (fluorescence of Fluo3-loaded cells) evoked by the ATP analog alpha beta
      methylene ATP. A high proportion of transformants expressed heteromeric receptors
      containing both P2X2 and P2X3 subunits, as evidenced by a nondesensitizing
      current in response to alpha beta methylene ATP. The method is fast and simple
      and could be generally useful for the stable expression of heteromultimeric
      channel proteins.

PMID- 9606711
TI  - Influence of detergents on the function of cloned potassium channels.
AB  - The influence of detergents on cloned potassium channels expressed in Xenopus
      oocytes was investigated. Bath application of Triton X-100 caused a dose
      dependent reduction of the peak current through the delayed rectifier channel
      rKv2.1 and a fast, time- and voltage-dependent, current inactivation. Onset of
      inactivation was observed at concentrations as low as 1 microM; at 100 microM
      inactivation proceeded with a time constant of about 50 ms at +50 mV. The effect
      of Triton did not compete with extracellular TEA and the tail current kinetics
      was accelerated, indicating that the molecular mechanism is not a simple open
      channel block. In patch-clamp recordings the effects were readily reversible and
      application of detergents from the inside were most effective. Triton induced
      similar effects in hKv1.5 channels; for rKv1.1., d-eag, and Kir2.1 mainly a
      current reduction was observed. No effect of 100 microM Triton was found for the
      plant inward rectifier channel KAT1. Investigation of Shaker channel mutants
      revealed a dependence of the Triton effect upon the degree and nature of C-type
      inactivation. Only detergents with a long hydrophobic carbohydrate chain and a
      hydrophilic chain of the polyethyleneglycol type caused inactivation of rKv2.1
      (e.g., Triton X-100, Thesit, Brij35 were active; CHAPS and MEGA-8 wre inactive).
      The presented data reveal that there are channel- and detergent-specific
      interactions which can result in fast inactivation leading to physiological
      effects similar to those exerted by local anesthetics and antiarrhythmic agents.

PMID- 9606712
TI  - Proposed arrangement of the seven transmembrane helices in the secretin receptor
      family.
AB  - An arrangement of the seven transmembrane alpha-helices of the G protein-coupled
      Secretin receptor family is proposed. The helices of 27 homologous receptor
      sequences were plotted as helical wheels. The solvent inaccessible portion of
      each helix was used to assign relative orientations. They were arranged according
      to two criteria: 1) conserved, hydrophilic residues and aligned positions with
      restricted volume changes face the other helices and 2) aligned positions with
      low identity and large volume change face the lipid. The positive inside rule
      confirms the assumption that loops connecting transmembrane helices I-II, III-IV,
      V-VI and the C-terminal part of the receptors are intracellular. Our model
      approach was tested using the Bacteriorhodopsin family. The use of volume changes
      at each position in the transmembrane helix was crucial for the good correlation
      of the orientation of the helices using the model approach and the structure of
      bacteriorhodopsin solved by electron microscopy [Grigorieff N, Ceska TA, Downing
      KH, Baldwin JM, and Henderson R (1996) J Mol Biol 259 393-421]. The tests of our
      modelling approach showed that six helices were within a 15 degrees derivation in
      the orientation and five helices were within a horizontal derivation of two
      residues. The largest orientational derivations of a helix were 40 degrees and
      the largest horizontal displacement was four residues. A long stretch of side
      chains predicted to possess low resistance to movement in helix V of the Secretin
      receptor family suggests an involvement in receptor activation. Comparison of the
      Secretin receptor family and the larger G protein-coupled Rhodopsin family showed
      many similarities, despite the lack of obvious sequence identity.

PMID- 9606713
TI  - Trimeric G alpha beta gamma protein coupling to a 3D model of G protein-coupled
      receptors confirming a new molecular mechanism for activation.
AB  - The present-day model for G protein activation and the associated theory on how a
      G protein-coupled receptor may activate the G protein are summarized.
      Experimental data are outlined which seem not to be in accordance with this
      present-day model. An alternative molecular mechanism for ternary complex
      activation is presented together with a three-dimensional model for a receptor
      coupled to the appropriate trimeric G protein. This 3D structure confirms our new
      molecular mechanism of activation.

PMID- 9606714
TI  - From histamine H2 receptor regulation to reclassification of H2 antagonists;
      inverse agonism as the basis for H2 receptor upregulation.

PMID- 9606715
TI  - Essential role of leucine222 in mediating signal transduction of the human
      angiotensin II type 1 receptor.
AB  - The angiotensin II (Ang II) type I receptor (AT1) is a member of the superfamily
      of heptahelical, G protein-coupled receptors (GPCRs) characterized by hydrophobic
      transmembrane domains connected by extra- and intracellular hydrophilic loops.
      The third intracellular loop (IC3) of many GPCRs is thought to directly interact
      with G proteins. We examined the molecular environment of the basic sequence
      KA221L222KK found in the IC3 of the human AT1 (hAT1) receptor by substituting
      Ala221 for Glu/Gln or Leu222 for Arg/Gln and determined the pharmacological
      properties of the resulting mutant receptors. Competitive binding experiments
      with the antagonist [Sar1,Ile8]Ang II revealed that COS-7 or stably expressing
      CHO cells transfected with either the wild-type or mutant receptors, produced a
      single population of high affinity binding sites (Kd of 0.5 nM) but variable
      receptor levels depending on cell type; Bmax approximately 100,000 sites/cell
      (COS-7), approximately 20,000 sites/cell (CHO). However, in competitive binding
      experiments using the agonist Ang II, both the wild type and the Ala-->Glu mutant
      displayed binding affinities of 1 nM, while the Leu-->Arg mutant had a
      significantly lower affinity (4 nM). When the functionality of the mutant
      receptors was examined, a lowered production of inositol-1,4,5-trisphosphate was
      obtained upon stimulation of the Ala-->Glu and Ala-->Gln mutants when compared to
      the wild-type receptor. However, no significant production of Ins(1,4,5)P3 was
      detected for the Leu-->Arg and leu-->Gln mutants. Our results suggest that Leu222
      in the KALKK sequence of the IC3 of the hAT1 receptor, through not essential for
      antagonist binding, has an essential role in mediating interactions with G
      protein and in signal transduction.

PMID- 9606716
TI  - Two threonine residues in the M2 segment of the alpha 1 beta 1 GABAA receptor are
      critical for ion channel function.
AB  - The role of three threonine residues in the M2 hydrophobic region of the GABAA
      receptor has been investigated by replacing these polar residues with alanine at
      the 6', 10' and 13' positions of M2 in the GABAA alpha 1, and beta 1 subunits and
      co-expressing the mutated subunits in the baculovirus Sf9 insect cell system.
      GABA did not elicit a current in cells expressing either the 6' or 13' threonine
      to the alanine mutants. The mutant subunits formed intact heteromeric GABAA
      receptors as judged by the binding of [3H] muscimol or the relative level of
      alpha 1 protein present in the plasma membrane. In contrast, a chloride current
      was generated by GABA in cells expressing the 10' mutant receptor. However, the
      current decayed more rapidly to baseline in the continued presence of GABA in the
      10' mutant receptor than in the wild type receptor. The results are discussed in
      terms of the possible roles of the threonine residues in the ion conduction
      pathway.

PMID- 9606717
TI  - Stable, high-level expression of human serotonin receptors in L929 cells using an
      inducible expression system.
AB  - Heterologous expression of cloned receptor subtypes for screening programs has
      become a real necessity for a modern pharmaceutical company. As the expression
      levels obtained so far are often low or unstable, we addressed this problem by
      using an inducible promoter system, i.e. the interferon-inducible mouse Mxl
      promoter. Using the gene coding for chloramphenicol acetyltransferase (CAT) as a
      reporter gene, we tested the inducibility of this promoter in the murine cell
      line L929. We found that background expression was low and that a distinct
      interferon-induced expression could be obtained. CAT expression reached its
      maximum at approximately 15 ng CAT/mg protein after induction for 24 hr with 1000
      U/ml murine interferon-beta; the induction ratio was 150-fold. Next, L929 cells
      were transfected with four different human serotonin (5HT) receptor cDNAs (5HT1A,
      5HT2A, 5HT1D beta and 5HT1E) under the control of the same Mxl promoter fragment.
      Also in this case well-regulated serotonin receptor-expressing clones were
      isolated. Bmax values varied from 3100 fmol/mg protein for the 5HT2A receptor,
      3300 fmol/mg protein for the 5HT1D beta receptor, 9800 fmol/mg protein for the
      5HT1E receptor, and even up to 10,400 fmol/mg protein for the 5HT1A receptor.
      Furthermore, the expression levels were shown to remain stable during serial
      propagation for at least one year, demonstrating the usefulness of this
      expression system. In fact, the 5HT1D beta receptor-expressing cells were used in
      the characterization of a new antimigraine agent, viz. alniditan.

PMID- 9606718
TI  - The alpha and omega of G-protein coupled receptors: a novel method for
      classification. Part 2. Bin classification.
AB  - A novel way of classification of G-protein coupled receptors is presented that is
      only based on receptor sequence information by counting of amino acid residues.
      It involves the number of amino acid residues between the Asn residue in TM1 and
      the residue Cys in the loop between TM4 and TM5, the number of residues between
      the latter Cys residue and Pro residue in TM6, and the number of residues between
      the latter Pro and the last amino acid residue (called omega) in the sequence.
      The classification of 131 sequences, covering biogenic amine, opioid and
      somatostatin receptors, is visualized by means of a diagram which is referred to
      as a bin map. Each bin in the diagram encloses all the sequences that belong to
      one and only one receptor type or subtype. This so-called bin classification was
      obtained by means of the genetic algorithm methodology, which offers new
      opportunities for classifying proteins.

PMID- 9606720
TI  - Identification of class-determining residues in G protein-coupled receptors by
      sequence analysis.
AB  - G protein-coupled receptors (GPCRs) form a large superfamily of receptors that
      are characterised by a seven transmembrane helical motif. The functions they
      perform, such as binding ligands and G proteins, are related to the presence of
      certain amino acids in critical positions. We have developed a computational
      sequence pattern correlation technique for the recognition of such function
      determining residues. The method searches for residues that are conserved in one
      class of proteins with a certain function but are different in other classes. The
      basic idea is that such residues are probably involved in this particular
      function. This technique was used to find residues that play a role in the
      binding of endogenous as well as exogenous ligands to various receptors. Many of
      the residues that were detected have been experimentally determined as important
      for ligand binding. More importantly, however, we also detected residues that are
      interesting targets for future mutation studies aimed at elucidating the sequence
      function relationship in GPCRs. The information obtained may help improve three
      dimensional GPCR models and can be useful for the study of receptor-ligand
      interactions.

PMID- 9606719
TI  - ACR-3, a Caenorhabditis elegans nicotinic acetylcholine receptor subunit.
      Molecular cloning and functional expression.
AB  - The molecular cloning and functional co-expression of a novel nicotinic
      acetylcholine receptor (nAChR) non-alpha subunit gene, acr-3, is described.
      Previously we determined the sequence and demonstrated the functional co
      expression of acr-2, a nAChR non-alpha subunit gene from Caenorhabditis elegans.
      Analysis of the acr-2 genomic DNA revealed the existence of another potential
      nAChR subunit gene, acr-3, in the same orientation, only 281 bp downstream of acr
      2. A cDNA containing the entire acr-3 coding sequence was isolated by RT-PCR and
      sequenced. The predicted protein contains the conserved features typical of nAChR
      non-alpha subunits and most closely resembles other invertebrate nAChR non-alpha
      polypeptides. Unusually, the highly conserved glycine residue (equivalent to
      residue 240 in the Torpedo alpha subunit) upstream of transmembrane domain 2 (m2)
      is replaced by a serine residue in ACR-3. When acr-3 cDNA was injected alone into
      Xenopus oocytes no levamisole-gated channel activity was observed. However when
      co-expressed with a C. elegans alpha subunit (UNC-38), ACR-3 contributed to the
      formation of levamisole-gated channels. The response of this hetero-oligomer to
      levamisole (100 microM) was reduced by the nAChR antagonists mecamylamine (1
      microM) and d-tubocurarine (10 microM).

PMID- 9606721
TI  - Drug accumulation in the presence of the multidrug resistance pump: dissociation
      between verapamil accumulation and the action of P-glycoprotein.
AB  - We studied the interaction between the multidrug transporter, P-glycoprotein, and
      two compounds that interact with it: vinblastine, a classical substrate of the
      pump, and verapamil, a classical reverser. Steady-state levels of accumulation of
      these two drugs were determined in a multidrug resistant P388 leukemia cell line,
      P388/ADR. The time course of accumulation of these drugs, and the effect of
      energy starvation and the presence of chloroquine on the level of their steady
      state accumulation were quite disparate. Vinblastine inhibited the accumulation
      of verapamil whereas it enhanced the accumulation of daunomycin, another classic
      substrate of P-glycoprotein. Verapamil did not compete with the intracellular
      binding sites of vinblastine. In all these aspects, vinblastine behaved as a
      typical substrate of P-glycoprotein but verapamil did not. Our data suggest that
      verapamil is a reverser of P-glycoprotein but that its intracellular accumulation
      is not affected by this membrane-bound transporter.

PMID- 9606722
TI  - Inactivation of the G alpha i2 and G alpha o genes by homologous recombination.
AB  - G proteins couple receptors to effectors and thus regulate multiple biological
      processes. Here we report on the phenotypes of G alpha i2-deficient and G alpha o
      deficient mice. G alpha i2-deficient mice display a blunted inhibitory regulation
      of adenylyl cyclase, alterations in T cell maturation and function, a growth
      retardation and also develop a lethal diffuse colitis with clinical and
      histopathological features closely resembling ulcerative colitis in humans,
      including the development of adenocarcinoma of the colon. G alpha o-deficient
      mice are also viable, but significantly smaller than wild-type controls.

PMID- 9606723
TI  - Molecular mechanisms of G protein-coupled receptor signaling: role of G protein
      coupled receptor kinases and arrestins in receptor desensitization and
      resensitization.
AB  - Dynamic regulation of G protein-coupled receptor signaling demands a coordinated
      balance between mechanisms leading to the generation, turning off and re
      establishment of agonist-mediated signals. G protein-coupled receptor kinases
      (GRKs) and arrestin proteins not only mediate agonist-dependent G protein-coupled
      receptor desensitization, but also initiate the internalization (sequestration)
      of activated receptors, a process leading to receptor resensitization. Studies on
      the specificity of beta-arrestin functions reveal a multiplicity of G protein
      coupled receptor endocytic pathways and suggest that beta-arrestins might serve
      as adaptors specifically targeting receptors for dynamin-dependent clathrin
      mediated endocytosis. Moreover, inactivation of the GRK2 gene in mice has lead to
      the discovery of an unexpected role of GRK2 in cardiac development, further
      emphasizing the pleiotropic function of GRKs and arrestins.

PMID- 9606724
TI  - Fluorescent labeling of NK2 receptor at specific sites in vivo and fluorescence
      energy transfer analysis of NK2 ligand-receptor complexes.
AB  - A fluorescent unnatural amino acid was introduced biosynthetically at known sites
      into the G protein-coupled neurokinin (tachykinin) NK2 receptor by suppression of
      UAG nonsense codons with the aid of a chemically misacylated synthetic tRNA
      specifically designed for the incorporation of unnatural amino acids during
      heterologous expression in Xenopus oocytes. A systematic UAG-scanning mutagenesis
      in NK2 extra- or intracellular loops and proximal transmembrane domains
      established that readthrough at some UAG sites may represent a limitation to the
      range of applicability of the nonsense suppression methodology. Fluorescence
      labeled NK2 mutants containing an unique fluorescent nitrobenzoxadiazoyl
      diaminopropionic acid residue at known sites were shown to be functionnally
      active. Intermolecular distances were determined by measuring the fluorescence
      resonance energy transfer (FRET) between the fluorescent unnatural amino acid and
      a fluorescently labeled NK2 heptapeptide antagonist in a native membrane
      environment. These distances confirmed the seven transmembrane topology for G
      protein-coupled receptors and determined a structural model for NK2 ligand
      receptor interactions. The peptide is inserted between the fifth and sixth
      transmembrane domains, thus suggesting that antagonism may be caused by
      preventing correct packing of the helices required for receptor function.

PMID- 9606725
TI  - Inverse agonism at adrenergic and opioid receptors: studies with wild type and
      constitutively active mutant receptors.
AB  - Ligands which display inverse agonism at G protein-coupled receptors do so by
      decreasing the intrinsic ability of a receptor to active the cellular G protein
      population in the absence of an agonist ligand. Expression of the murine delta
      opioid receptor in Rat-1 fibroblasts resulted in the inverse agonist ICI174864
      being able to cause inhibition of basal high affinity GTPase activity and of the
      binding of [35S]GTP gamma S in membranes of a clone (D2) of these cells which
      expresses high levels of the receptor. These effects were blocked by co-addition
      of the neutral antagonist TIPP[psi], demonstrating a requirement for the delta
      opioid receptor, and by pertussis toxin pretreatment of the cells, showing them
      to be produced via a Gi-like G protein. The inverse agonist properties of
      ICI174864 could also be demonstrated in whole cells. Stimulation of forskolin
      amplified adenylyl cyclase activity was produced by ICI174864 following
      [3H]adenine prelabelling of the cells. Constitutively activated mutants of
      receptors should provide a convenient means to detect inverse agonists.
      Incubation of cells either transiently or stably transfected with a
      constitutively activated mutant of the human beta 2-adrenoceptor with the beta 2
      inverse agonists betaxolol or sotalol, which are both able to inhibit CAM beta 2
      adrenoceptor-mediated basal adenylyl cyclase activity, resulted in a strong
      upregulation of levels of the receptor. In the stable cells lines this effect was
      prevented by co-incubation with neutral antagonists but could not be reproduced
      by an adenylyl cyclase P-site ligand which also inhibited basal adenylyl cyclase
      levels.

PMID- 9606726
TI  - Molecular pharmacology of neural melanocortin receptors.
AB  - The cloning of melanocortin receptors opened new avenues to identify selective
      ligands for this receptor family. gamma-MSH was characterized as a melanocortin-3
      receptor selective agonist, [D-Arg8]ACTH-(4-10) and [Pro8,10, Gly9]ACTH-(4-10)
      were characterized as melanocortin-4 receptor antagonists. The application of
      these ligands in vivo revealed that melanocortin-4 receptors mediate melanocortin
      induced grooming behaviour in the rat. Since we still lack potent and selective
      melanocortin receptor ligands, we performed homology modelling and site directed
      mutagenesis of the melanocortin-4 receptor, in order to understand how
      melanocortins bind melanocortin receptors. A histidine at position 260 in the
      melanocortin-4 receptor is important for normal receptor function. However this
      residue is not forming a salt bridge with a glutamate at position 92 to keep the
      receptor in an inactive conformation, nor with the glutamate in the melanocortin
      peptides as had been suggested before.

PMID- 9606727
TI  - Autoradiographic mapping of 5-HT1B- and 5-HT1D receptors in human brain using
      [3H]alniditan, a new radioligand.
AB  - [3H]alniditan, a new potent non-indole serotonin 5-HT1B/1D agonist, was used as a
      radioligand to characterize 5-HT1B and 5-HT1D receptor (previously termed 5-HT1D
      beta and 5-HT1D alpha) in various regions of the human brain. Quantitative
      receptor autoradiography was applied for high anatomical resolution and
      sensitivity. Highest densities of 5-HT1B/1D receptors were found in the
      substantia nigra and in the globus pallidus. High to moderate densities were
      measured in the caudate nucleus, putamen, nucleus accumbens, central gray and
      hippocampal formation. Very low densities were detected in various cortical
      regions. In the cerebellum no [3H]alniditan binding was detected. Selective 5
      HT1B receptor labeling was achieved using [3H]alniditan in the presence of 300 nM
      of ketanserin (sufficient to block 5-HT1D receptor labeling). The identity of the
      5-HT1B binding sites under these conditions was corroborated by the pIC50 of
      sumatriptan, which corresponded to its affinity for cloned human 5-HT1B receptors
      expressed in cells. Surprisingly, the distribution of selective 5-HT1B receptor
      labeling was completely identical to the distribution of labeling of 5-HT1B + 5
      HT1D receptors. The present data indicate that [3H]alniditan is a suitable
      radioligand for measuring 5-HT1B/1D receptor in the human brain and that the 5
      HT1B binding sites are predominant in the presently investigated regions of the
      human brain.

PMID- 9606728
TI  - Molecular regulation of opioid receptors.
AB  - Opioid actions are initiated at membrane receptors which couple to cellular
      effectors through G protein-mediated pathways. In the central nervous system
      opioids reduce neuronal activity through the inhibition of voltage-dependent Ca2+
      channels, the activation of K+ channels and the inhibition of adenylyl cyclase. A
      significant clinical limitation to opioid therapy is the development of
      tolerance, a biological event that has been linked to agonist effects at the
      receptor level. Molecular studies on the consequences of opioid receptor
      regulation will provide a better understanding of the cellular mechanisms
      involved in the agonist-mediated events in tolerance development.

PMID- 9606729
TI  - NMR investigations of recombinant 15N/13C/2H-labeled bradykinin bound to a Fab
      mimic of the B2 receptor.
AB  - NMR spectroscopy has been used to obtain structural information on the bioactive
      conformation of the nonapeptide hormone bradykinin (Arg-Pro-Pro-Gly-Ser-Pro-Phe
      Arg, BK) bound to the Fab-fragment of an antibody that mimics the hormone binding
      site of the natural bradykinin B2-receptor. Using 15N or 15N,13C, 60% 2H isotope
      labelled bradykinin, complete 1H, 13C and 15N assignments for bradykinin bound to
      the Fab-fragment have been obtained. Preliminary interpretation of 15N edited NOE
      spectra indicates that the conformation of bradykinin bound to the model receptor
      differs substantially from previous computer models of the bioactive conformation
      of bradykinin.

PMID- 9606730
TI  - Acute renal failure following bone marrow transplantation.
AB  - Acute renal failure (ARF) is one of the most frequent and potentially life
      threatening complications following bone marrow transplantation (BMT). Several
      renal syndromes that occur are either unique or occur with a disproportionate
      frequency post-BMT. Clinically ARF can be classified according to the time of
      onset post-BMT. Immediate ARF syndromes include tumor lysis syndrome and marrow
      infusion associated toxicity, which usually occur within 5 days post-BMT.
      Hepatorenal-like syndrome secondary to venoocclusive disease occur within one
      month and is the most common cause of early ARF syndrome. The late renal
      syndromes, more than 4 weeks post-BMT, include BMT-associated nephropathy, which
      may be acute or chronic, and cyclosporin nephrotoxicity. Other non-specific
      causes of ARF such as sepsis, hypotension, volume depletion, nephrotoxic agents
      and obstructive uropathy can also occur at any time period. Frequently ARF is
      multifactorial in these patients with complicated clinical course. Therapeutic
      approach depend on the underlying etiology. Supportive treatment such as
      optimization of volume status and dialysis when indicated are important steps as
      specific therapy is rarely available. Therefore, efforts should be targeted to
      the prevention of ARF. This includes prophylaxis for tumor lysis syndrome and
      marrow infusion toxicity by hydration and alkaline diuresis, avoiding nephrotoxic
      agents, early recognition and treatment of infection and correction of volume
      depletion.

PMID- 9606731
TI  - Can pentoxifylline prevent renal disease?
AB  - The characteristics of pentoxifylline(Trental) suggest that it is an ideal agent
      to be used as adjunct in the therapy of chronic proliferative
      glomerulonephritides. Theoretical considerations suggest that pentoxifylline
      should also protect against and even ameliorate tubulo-interstitial fibrosis of
      affected kidneys.

PMID- 9606732
TI  - The relationship between sodium chloride concentration and bile acid cytotoxicity
      in cultured kidney cells.
AB  - Patients with obstructive jaundice suffer an increased incidence of mortality
      from post operative renal failure, which may be related to elevated circulating
      bile salts. This study assesses the effects of increased ionic strength (similar
      to that found in the kidney inner medulla) on bile salt critical micellar
      concentration (CMC) and cytotoxicity to renal medullary epithelial primary
      cultures and MDCK and NRK cell lines representing the distal and proximal tubular
      cells respectively. The CMC of chenodeoxycholic acid decreased from 2.86 +/- 0.07
      (in isotonic Earle's Hepes buffer) to 2.30 +/- 0.07, 1.99 +/- 0.09 and 1.46 +/-
      0.08 mM following the addition of 150, 250 and 500 mM NaCl. Similarly, the CMC of
      deoxycholic acid was reduced from 3.18 +/- 0.1 to 2.84 +/- 0.1, 2.26 +/- 0.1 and
      1.79 +/- 0.09 mM by the addition of 150, 250 and 500 mM NaCl. Increasing the
      ionic strength of the culture medium of medullary epithelial cells by the
      addition of 150 mM NaCl, decreased viability by 39% (p < 0.01), 24% (p < 0.001)
      and 40% (p < 0.001) for lithocholic (25 microM), chenodeoxycholic (100 microM)
      and deoxycholic acids (100 microM), respectively. A similar increase in the ionic
      strength of the culture medium of MDCK cells decreased viability by 79% (p <
      0.01), 46% (p < 0.01) and 15% (p < 0.01) for lithocholic (15 microM),
      chenodeoxycholic (100 microM) and deoxycholic (50 microM), respectively. Adding
      200 mM urea to medium supplemented with 150 mM NaCl (to further increase
      osmolality but not ionic strength) had no effect on the cytotoxicity bile salts
      in MDCK cells. The addition of 150 mM NaCl to the culture medium of NRK cells
      resulted in a decrease viability of 15% (p < 0.01), 27% (p < 0.01) and 60% (p <
      0.01) following exposure to either lithocholic (15 microM), chenodeoxycholic (50
      microM) or deoxycholic acids (50 microM) respectively. These results show that
      increasing NaCl concentrations lowers CMC of bile salts and increase cytotoxicity
      in medullary epithelial primary, MDCK and NRK cells. This suggests that the high
      NaCl levels in the kidney inner medulla would reduce bile salt CMC such that they
      could damaged renal cells. This may, in part, explain the increased
      susceptibility of the kidney during obstructive liver disease.

PMID- 9606733
TI  - Effects of captopril on morphologic changes in kidney of spontaneously
      hypertensive rats with adriamycin nephropathy.
AB  - Antihypertensive therapy has been shown to slow down the progression of chronic
      renal failure. Angiotensin converting enzyme inhibitors and calcium antagonists
      have been emphasized as the agents with the most protective effect. Our previous
      study showed that captopril slowed down renal function deterioration in the early
      course of adriamycin (ADR) nephropathy in spontaneously hypertensive rats (SHR).
      The present study was undertaken with the aim to examine morphologic changes
      associated with that slower renal function deterioration. Adult (24 weeks) female
      SHR were randomly divided into the following groups: the control group (n = 12)
      was given tap water to drink; the adriamycin (ADR) group (n = 25) was treated
      with ADR; the ADR-captopril (ADR-C) group (n = 27) was treated with ADR and
      thereafter with captopril (60 mg/kg/day). Rats were sacrificed at weeks 6, 12 and
      18 and histologic analysis was semiquantitatively performed. In the control group
      the glomeruli exhibited only minor changes at the end of the study. In the ADR
      group slight glomerular mesangial hypercellularity appeared in the sixth week and
      progressed in focal and segmental sclerosis. Some glomeruli showed segmental
      proliferation and increased fibrular matrix of a tuft adherent to a fibrocellular
      crescents. In the ADR-C group, glomeruli with a slight increase of mesangial
      matrix were seen at the end of the sixth week, mesangial hypercellularity
      developed until the end of the sixth week, mesangial hypercellularity developed
      until the end of the 12th week and segmental glomerulosclerosis until the end of
      the study. Semiquantitative analysis revealed that the mean semiquantitative
      scores for mesangial expansion and glomerular sclerosis were significantly lower
      in ADR-C group than in ADR group throughout the study. We concluded that
      captopril slowed down mesangial expansion and reduced the development of
      glomerular sclerosis.

PMID- 9606734
TI  - Nitric oxide-mediated renal epithelial cell injury during hypoxia and
      reoxygenation.
AB  - The potent endothelial-derived vasodilator nitric oxide (NO) has been identified
      as a protective agent in acute renal failure. However, some recent studies have
      suggested a detrimental effect of NO on rat proximal tubules exposed to hypoxia
      and reoxygenation. We determined whether NO metabolites cause intracellular
      oxidation during hypoxia and reoxygenation and whether this oxidative stress is
      linked to irreversible cell injury. Primary cultures of rat proximal tubular
      epithelial cells were studied in a subconfluent stage and subjected to 60 min
      hypoxia and 30 min reoxygenation. Intracellular oxidation was assessed by
      monitoring the conversion of nonfluorescent dihydrorhodamine 123 (DHR) to
      fluorescent rhodamine 123 as a probe for the long-lived oxidant peroxynitrite.
      Hypoxia and reoxygenation produced a marked increase in cellular generation of
      oxidant species. Intracellular oxidation of DHR was reduced by approximately 40%
      when cells were also exposed to the NO synthase inhibitor L-NAME. Oxidation of
      DHR following hypoxia and reoxygenation was not affected by SOD or DMTU. A
      combination of SOD and L-NAME was no more effective than L-NAME alone. Hypoxia
      and reoxygenation produced substantial injury (as LDH release). There was a 40%
      reduction in LDH release when cells were pretreated with a NO synthase inhibitor.
      In summary, increased generation of NO capable of inducing intracellular
      oxidizing reactions and cell death occurred during renal hypoxia and
      reoxygenation.

PMID- 9606735
TI  - The effect of silibinin on experimental cyclosporine nephrotoxicity.
AB  - The immunosuppressive drug cyclosporine A (CsA), is metabolized by cytochrome P
      450 IIIA. It causes acute reversible as well as chronic largely irreversible
      nephrotoxic effects. This effect is bases on vasoconstriction of the afferent and
      efferent glomerular arterioles which leads to a reduction in glomerular plasma
      flow and glomerular filtration rate. The mechanisms of the vasoconstriction are
      unclear with a number of different pathways under discussion. Silibinin is the
      main constituent of silymarin. Silibinin inhibits lipid peroxidation on hepatic
      microsomes and mitochondria of rats and is also able to reduce the activity of
      various monooxygenases. Cyclosporin-induced lipid peroxidation and affected
      cytochrome P-450 may even contribute to cyclosporine nephrotoxicity. We examined
      the possibility that silibinin had a protective effect as a result of its radical
      scavenging properties. Silibinin, 5 mg/kg BW i.p., was administered 30 min before
      cyclosporine application at dose of 30 mg/kg BW daily i.p. The biochemical
      parameters, total malondialdehyde (MDA) in whole blood and kidney homogenates and
      specific content of cytochrome P-450 in microsomal liver suspension were
      estimated. Three groups were studied: controls (con), cyclosporine alone (CsA),
      and cyclosporine plus silibinin (CsA + Sili). Creatinine was significantly
      increased after 2 weeks in both cyclosporine treated groups compared to controls
      (CsA 60.2 +/- 10.6 versus 45.8 +/- 10.4 mumol/L, p < 0.05; and CsA + Sili 72.0 +/
      8.3 versus 45.8 +/- 10.4 mumol/L, p < 0.001) and glomerular filtration rate
      (GFR) was significantly decreased (p < 0.0001) in the same groups. Total MDA was
      elevated only in CsA rats (2.26 +/- 0.35 mumol/L, p < 0.05) in comparison with
      controls (1.60 +/- 0.44 mumol/L, p < 0.05) and with rats treated by CsA + Sili
      (1.65 +/- 0.27 mumol/L, p < 0.05). The specific content of cytochrome P-450 in
      microsomal liver suspension was increased in group CsA + Sili (1.179 +/- 0.115
      nmol/mg prot) compared to control group (0.775 +/- 0.086 nmol/mg prot., p < 0.05)
      and also CsA group (0.806 +/- 0.098 nmol/mg prot., p < 0.05). In conclusion,
      silibinin decreased cyclosporine-induced lipid peroxidation without a protective
      effect on GFR. These data indicate that this pathway is not be important in
      cyclosporine-induced nephrotoxicity. Administration of both drugs (CsA + sili)
      increased the specific content of cytochrome P-450 in liver microsomes. This
      suggests that the effect of silibinin on cyclosporine biotransformation in the
      liver is via cytochrome P-450.

PMID- 9606736
TI  - Preventive effect of ACE inhibitor on interstitial myofibroblast formation and
      matrix deposition in a nephrotic model.
AB  - The nephrotic mouse (ICGN strain) is a useful model for progressive nephrotic
      syndrome (NS). In the present study, we demonstrated the preventive effects of
      enalapril, an angiotensin converting enzyme (ACE) inhibitor, on the progression
      of renal dysfunction and tubulo-interstitial fibrosis in the NS mice.
      Administration of enalapril (5 mg/dL in drinking water) to the 4-week-old NS mice
      for a 4-week-period did not improve their nephrotic symptoms such as albuminuria
      and hypoalbuminemia, but significantly suppressed the increases in blood urea
      nitrogen and serum creatinine levels. Renal histopathology demonstrated that the
      administration of the ACE inhibitor significantly attenuated the progression of
      the tubular and interstitial lesions (tubular dilatation, luminal cast
      accumulation and interstitial expansion) rather than the glomerular sclerotic
      changes. The suppression of the increase in blood urea nitrogen level by
      enalapril depended on the attenuated tubular injury rather than on the unchanged
      glomerular matrix deposition. Immunohistochemical examination revealed that the
      administration of the ACE inhibitor suppressed the formation of myofibroblasts,
      identified by the alpha-smooth muscle actin-positive cells, in the interstitial
      spaces. Consequently, interstitial matrix deposition was significantly reduced in
      the NS mice treated with enalapril. From the results obtained with the
      spontaneous nephrotic model, we emphasize a possibility that ACE inhibitor may be
      effective for attenuating progression of renal dysfunction and fibrosis in human
      NS, even if the ACE inhibitor fails to improve nephrotic symptoms such as
      albuminuria and hypoalbuminemia.

PMID- 9606737
TI  - Acetate-free biofiltration for acute renal failure.
AB  - The characteristics of acetate-free biofiltration (AFB) are now well documented
      in patients with chronic renal failure: hemodynamic tolerance, correction of acid
      base imbalance, buffer-free dialysate (without acetate) and absence of
      backfiltration. This hemodialysis technique can be beneficial to patients with
      acute renal failure (ARF). In our intensive care unit, we prospectively studied
      29 patients with isolated ARF or ARF associated with failure of other organs. All
      eligible patients were randomly assigned to undergo dialysis with bicarbonate
      hemodialysis (BH) or with (AFB). All used the same high flux biocompatible
      dialysis membranes. Effectiveness and hemodynamic tolerance of hemodialysis
      sessions and evolution of patients were analyzed. Correction of metabolic
      disorders, although better in the AFB group was not statistically different from
      that in the BH group. Re-equilibration of acid-base balance was also similar,
      with or without mechanical ventilation. Heparin consumption was significantly
      higher in the AFB group, with no effect on haemorrhagic complications. Analysis
      of hypo- and hypertensive episodes, defined as arterial pressure (AP) variations
      20% greater than initial pressure, showed no difference in terms of number or
      degree of AP variation. However, weight loss and the rate of ultrafiltration led
      to a higher hypotensive risk in the BH group (p < 0.05). Finally, the clinical
      course and prognosis was similar in both groups. In summary, AFB may be
      considered as effective a hemodialysis technique as BH in patients with ARF.
      Weight loss was better tolerated in the AFB group and can be a favorable factor
      considering the deleterious effect of overhydration in patients admitted to an
      intensive care unit. This study invites a comparison of longer dialysis session
      of AFB therapy and continuous hemodiafiltration.

PMID- 9606738
TI  - Retinol and alpha-tocopherol in hemodialysis patients.
AB  - The biological effects of reactive oxygen species and other radicals controlled
      by antioxidant mechanisms are modified by various enzymes and other substrates.
      Antioxidant substrates are divided into those with lipophilic and hydrophilic
      groups. Retinol and tocopherol are the main representations of lipophilic
      antioxidants. The aim of the present study was to describe the changes of retinol
      and alpha-tocopherol which occurred in hemodialysis (HD) patients in respect to
      the influence of antioxidant systems. The experimental group consisted of 14
      patients on regular HD treatment. The control group consisted of 14 healthy blood
      donors. HPLC was used to measure retinol and alpha-tocopherol in serum. We found
      that the retinol concentration was significantly higher in HD patients compared
      to controls (2.35 +/- 0.95 versus 0.90 +/- 0.23 mg/L, p < 0.0001). The
      concentration of alpha-tocopherol in serum was not different in both study groups
      (7.32 +/- 3.01 versus. 8.94 +/- 3.57 mg/L). A review of the MEDLINE database
      since 1985 found a few references concerning these important antioxidant vitamins
      in HD patients and these contained contrasting results. It has been suggested
      that some of the complications related to HD including cardiovascular
      complications, anemia and atherosclerosis may be due to ineffective antioxidant
      systems and/or to increased free oxygen radical production. The question about
      supplementation of antioxidants in HD patients is open although there are some
      positive data regarding the use of moderate and safe selenium supplementation in
      HD patients. HD patients treated by erythropoietin had increased plasma
      concentration of retinol and normal level of alpha-tocopherol compared to healthy
      group. However, this positive finding did not affect lipid peroxidation, which is
      increased in HD patients and leads to some complications during HD treatment.

PMID- 9606739
TI  - Changes in frequency and etiology of acute renal failure in pregnancy (1980
      1997).
AB  - In recent years, the incidence of acute renal failure (ARF) in pregnancy has
      decreased in developed countries. This cause of this decline has been reported to
      be liberalized abortion laws and improved prenatal care. The aim of this study
      was to determine if the incidence and etiology of ARE in pregnancy in our
      population had undergone similar changes. Between January 1, 1980 and January 1
      1997 the number of the patients with ARF was 487. In 74 (15%) of these patients,
      the etiology of ARF was associated with pregnancy. The frequency of ARF in
      pregnancy was 17.4% between January 1980 and August 1985, 15.4% between September
      1985 and November 1989, 13.5% between December 1989 and January 1997. The
      differences between the frequencies were not statistically significant (p > 0.5).
      In the present series, the various disorders leading to ARF in pregnancy were
      abortion (30%), HELP syndrome and pre-eclampsia (14%), pre-eclampsia or eclampsia
      (12%), postpartum hemorrhage (15%), fetal death (12%), abruption placentae (6%)
      and placentae previa (1%).

PMID- 9606740
TI  - Clinical course and symptomatic prediagnostic period of patients with Wegener's
      granulomatosis and microscopic polyangiitis.
AB  - The clinical course of 15 patients with Wegener's granulomatosis (WG) and eight
      patients with microscopic polyangiitis (MPA) from one nephrological clinical
      center is presented for the period from 1984 to 1993, when testing for
      antineutrophil cytoplasmic antibodies (ANCA) was gradually introduced into
      routine clinical practice. We found a high degree of prolonged time periods with
      symptoms attributable to WG or MPA until the specific diagnosis was made. Nine
      patients with WG and one patient with MPA had symptomatic prediagnostic periods
      of more than three years, which extended in one case up to twenty years. In these
      prediagnostic periods, often even severe flares of vasculitic activity resulted
      in spontaneous remission without immunosuppressive therapy. One patient on
      chronic dialysis for four months because of rapidly progressive
      glomerulonephritis, experienced sufficient spontaneous regain of residual renal
      function to stay off dialysis for 6 years. Despite a high amount of spontaneous
      recovery, recurrent flares of disease eventually led to death in those cases
      without sufficient immunosuppressive therapy. Contrary to long courses of
      disease, one patient with WG had a fulminate exacerbation of disease with lethal
      hemoptysis after a prediagnostic period of only three months. Renal disease,
      respiratory and other symptoms did not occur sequentially, but each could precede
      the other. We conclude in agreement with published former experience, that WG and
      MPA show a highly variable spontaneous disease course, that requires extended
      observational periods for evaluating maintenance therapies.

PMID- 9606741
TI  - Acute renal failure after massive ingestion of gliclazide in a suicide attempt.
AB  - Gliclazide, a sulfonlyurea class molecule, is used to control glycaemic levels in
      non-insulin-dependent diabetes mellitus. Acute and chronic toxicity studies,
      conducted in various animal species, have demonstrated a very low toxicity. We
      report a patient who developed acute renal failure due to acute tubular necrosis
      following a massive ingestion of gliclazide in an suicide attempt. The patient
      ingested 28 grams of gliclazide; the normal dose of gliclazide is 80 mg one or
      twice a day. At admission the patient was hypoglycaemia and in a few days became
      oliguric with an increase in the serum creatinine concentration, but with a
      normal blood urea nitrogen level. He underwent dialysis and ten days after
      ingestion of gliclazide, his renal function improved rapidly.

PMID- 9606742
TI  - Is oxidative stress the biochemical basis of uranyl nitrate-induced acute renal
      failure?

PMID- 9606743
TI  - Acute oligoanuric renal failure in dextran 40 treated patients.

PMID- 9606744
TI  - Protein intake in patients with acute renal failure.

PMID- 9606745
TI  - Control of pulsatile LH secretion during seasonal anoestrus in the ewe.
AB  - The seasonality of reproductive activity in the ewe in temperate latitudes is
      controlled by photoperiod. Its annual variations control the temporal
      organization of the sexual cycle by changing the activity of the gonadotrophic
      axis. Cyclic oestrous behaviour usually appears in the ewe at the end of summer
      or the beginning of autumn and finishes in winter or at the very beginning of
      spring. Seasonal anoestrus is characterized by the absence of ovulation and
      sexual behaviour. During seasonal anoestrus, a decrease in LH pulse frequency is
      observed. The inhibition of pulsatile LH secretion is maintained throughout the
      anoestrous season and is responsible for the low reproductive activity during
      this period. Variation in the seasonal inhibition of LH pulsatility results from
      an increase in the negative feedback by oestradiol on LH pulse frequency during
      the long days of spring and summer. The inhibition of LH secretion involves
      increased action of dopamine in the hypothalamus on the chain of nervous elements
      which controls gonadotrophic activity. Among the various dopaminergic structures,
      the retrochiasmatic A15 nucleus is involved in the inhibitory control of LH
      pulsatility by oestradiol during the long day period. Oestradiol increases the
      dopaminergic tone of the A15 nucleus in ovariectomized ewes during the long day
      period. In this structure, the effect of oestradiol on the dopaminergic
      metabolism probably results from a direct, local activation. In the sheep,
      dopamine might also participate in the inhibition of gonadotrophin activity
      during other periods of reproductive life.

PMID- 9606746
TI  - Trans isomers of long-chain n-3 polyunsaturated fatty acids in tissue lipid
      classes of rats fed with heated linseed oil.
AB  - The isomerization of linolenic acid into mono- and di-trans isomers takes place
      during heat treatment. One of these compounds, 18:3 delta 9c, 12c, 15t can be
      desaturated and elongated to form, in particular, the trans isomers of
      eicosapentaenoic and docosahexaenoic acids. This study was undertaken to observe
      the incorporation of these trans long-chain n-3 polyunsaturated fatty acids into
      the lipid classes of several tissues. Rats were fed for 8 weeks with heated
      linseed oil containing high levels of trans linolenic acid isomers. The lipid
      classes of the liver, kidney, heart and adrenals of these rats contained various
      levels of these compounds. The 20:5 delta 5c, 8c, 11c, 14c, 17t represented
      between 80 and 90% of the total 20:5 in the phospholipids, but 22:5 delta 7c,
      10c, 13c, 16c, 19t and mainly 22:6 delta 4c, 7c, 10c, 13c, 16c, 19t were only
      present in small quantities. This may indicate that the cis fatty acids are
      better metabolized in these cases. Among the tissues studied, it was interesting
      to note a high level of 22:5 delta 19t in the adrenals, particularly in
      cholesterol esters.

PMID- 9606747
TI  - Effect of a high linoleic acid diet on delta 9-desaturase activity, lipogenesis
      and lipid composition of pig subcutaneous adipose tissue.
AB  - The effects of three diets were compared: a high linoleic acid diet (diet M
      containing 4% maize oil), diet T containing 4% beef tallow, and C, a conventional
      control diet, on delta 9-desaturase activity and lipogenesis in pig subcutaneous
      adipose tissue. Diet M increased lipogenesis (estimated from the activities of
      acetyl-CoA-carboxylase, malic enzyme and glucose-6-phosphate dehydrogenase), and
      decreased delta 9-desaturase activity, in comparison to the other diets. Linoleic
      acid content was higher in the pigs fed diet M than in the other pigs (amounting
      to 26% of total tissue fatty acids versus 15%, respectively). The lower
      monounsaturated fatty acid content in adipose tissue of pigs fed diet M compared
      to pigs fed other diets could be associated with the lower delta 9-desaturase
      activity and the lower oleic acid content of diet M. The present study suggests
      that delta 9-desaturase could be involved in the regulation of monounsaturated
      fatty acid content and hence in the quality of pig adipose tissue.

PMID- 9606748
TI  - [Relationship between digestive repletion state and hepatic composition in
      gavaged mule ducks].
AB  - Two batches of male mule ducks were constituted on the basis of the filling state
      of the crop at slaughter, after being over-fed twice a day for 5 days: no corn in
      the crop defined 'OV' birds, and corn in the crop defined 'OP' birds. 'OP'
      animals presented significantly lower daily consumption during the last 3 days of
      force-feeding. They had a lighter liver weight than 'OV' ducks (178 versus 197
      g), lower hepatic lipid percentages (25.0 versus 33.0%), and enhanced hepatic
      glycogen rates (4.7 versus 2.4%). Metabolic state of animals might explain these
      variations in hepatic composition. Unadaptation to force-feeding modifies the
      metabolic inbalance of the overfed animals and consequently induces higher levels
      of carbohydrate. These results suggest that similar differences between crude
      fatty livers could be reflected in the quality of the cooked products.

PMID- 9606749
TI  - Effect of adding sugar beet fibre and wheat bran to a starch diet on the
      absorption kinetics of glucose, amino-nitrogen and volatile fatty acids in the
      pig.
AB  - The purpose of this study with the pig was to analyse the influence of the type
      of dietary fibre on quantitative kinetics of the absorption of nutrients deriving
      from enzymatic digestion in the small intestine and that of volatile fatty acids
      (VFA) deriving from microbial digestion in the hindgut influenced by the length
      of adaptation to the diet. Two groups of four pigs were fitted with a device for
      measuring absorption by simultaneous analysis of the differences in the porto
      arterial concentrations of nutrients and metabolites and of the portal blood flow
      rate. They received successively two diets containing fish- and heat-treated
      potato flour, balanced in vitamins and minerals, and only differing in the type
      of fibre added at the inclusion level of 10%: wheat bran (S) or sugar beet fibre
      (P). Following an adaptation period of 30 d (C) or 5 d (A) to each of these
      diets, and after the last experimental meal of 800 g, the animals were subjected
      for 12 h to blood samplings every 30-60 min for the analysis of glucose, amino
      nitrogen and volatile fatty acids (VFA) with a simultaneous recording of the
      portal blood flow-rate. The type of dietary fibre did not modify nutrient
      absorption (glucose and amino-nitrogen) but affected the amounts of VFA appearing
      in the portal blood. These amounts were higher (P < 0.001) after ingestion of the
      sugar beet fibre-rich diet (group PC + PA: 766 mmol/12 h) than after that of the
      wheat bran-rich diet (group SC + SA: 477 mmol/12 h). The proportion of acetic
      acid in the absorbed mixture rose (PC + PA 63.6% versus SC + SA 58.5%, P < 0.01)
      at the expense of propionic acid (PC + PA 27.4% versus SC + SA 31.0%, P < 0.01).
      Prolongation of the adaptation period from 5 to 30 d led to a decrease in the
      absorption of nutrients deriving from enzymatic digestion in the small intestine
      (glucose g/12 h: SA + PA 341.8 versus SC + PC 244.5, P < 0.01; amino-nitrogen
      g/12 h: SA + PA 29.4 versus SC + PC 21.0, P < 0.001) without any subsequent
      change in the absorption of the volatile fatty acids.

PMID- 9606750
TI  - [Degradation and uptake of 14C labeled casein peptides by mixed bacteria of the
      rumen].
AB  - This work studied the in vitro degradation by mixed rumen bacteria of various 14C
      labelled fractions of casein peptides, of known molecular size, added to a total
      unlabelled casein hydrolysate. Size exclusion HPLC was used in order to segregate
      the casein peptides according to their molecular weights. Radioactivity
      associated with the bacteria increased over time. The way 14C was incorporated
      into the bacteria depended on the size of the labelled peptides initially added.
      Small peptides (1 to 2 kDa) were very rapidly assimilated, whereas radioactivity
      coming from larger peptides (5 to 10 kDa) tended to accumulate far more slowly in
      the bacterial pellet. The disappearance rates of the radioactivity differed
      between the fractions. The longest peptides disappeared more quickly than the
      medium-sized ones, which in turn were hydrolysed more rapidly than the smallest
      ones. Here, the uptake of small peptides seems to be the limiting step of the
      peptides utilization by bacteria.

PMID- 9606751
TI  - The effect of supplemental propionate on insulin responsiveness to glucose and
      tissue responsiveness to insulin in relation to feeding in sheep.
AB  - Two glucose clamp techniques were performed for 6 h starting 2 h before the
      initiation of feeding to investigate the effect of dietary propionate
      supplementation on insulin responsiveness to glucose and tissue responsiveness to
      insulin in relation to feeding in rams. The rams were fed alfalfa hay without
      (Cont diet) and with 10 mmol.kg BW-1.d-1 of calcium propionate (Prop diet) for 4
      weeks in randomized order. With the hyperglycemic clamp, the ratio of plasma
      insulin increment to glucose infusion rate did not differ between the diets, but
      for the Prop diet the ratio was less during the pre-feeding period. With the
      hyperinsulinemic euglycemic clamp, the glucose infusion rate was lower (P < 0.05)
      for the Prop diet than the Cont diet, and increased (P < 0.05) after feeding. In
      rams supplemented propionate tissue responsiveness to insulin was reduced.
      Propionate supplementation may either impair glucose utilization in response to
      insulin infusion or enhance glucose production from propionate.

PMID- 9606752
TI  - [Measure of splanchnic blood flow by marker dilution: comparison of 4 methods of
      para-aminohippuric acid determination].
AB  - The objective of this study was to determine the influence of the analytical
      method of para aminohippuric acid (PAH) on splanchnic blood flows, as measured by
      a dye dilution method in ovines. Four different analytical methods of PAH were
      compared. They differed in the pretreatment of the samples and in the presence or
      absence of a deacetylation step to account for the partial acetylation of PAH in
      the liver (13%). The optimum conditions of deacetylation were defined as 60 min
      of incubation at 90 degrees C in presence of HCl (5N). The four analytical
      methods were checked to be linear (from 0 to 35 mg/L), repeatable (CV = 0.70%)
      and reproducible (CV = 2.1%). It appeared necessary to prepare the standards in
      the same matrix as that of the samples. The choice of the analytical method was
      responsible for differences in PAH concentrations and in the absolute values for
      portal and hepatic blood flows, which could reach 21%. The presence of a
      deacetylation step with HCl significantly reduced the contribution of the hepatic
      artery to the total hepatic blood flow (from 24 to 10%). Consequently, this study
      showed that the nature of the analytical method chosen can highly influence the
      measurements of splanchnic nutrient fluxes. The recommended analytical method is
      the one which includes a deacetylation step.

PMID- 9606753
TI  - Influence of different planes of energy supply prior to the breeding season on
      blood metabolites in female mink (Mustela vison).
AB  - Metabolic blood profiles were studied in a total of 30 female mink (Mustela
      vison) at different planes of nutrition prior to the breeding season in a control
      (CON; n = 10), a flushed (FLUSH; n = 10) and a negative energy balance group
      (NEG; n = 10). The animals were kept in metabolism cages or under normal farm
      conditions, respectively. The experiment, which was divided into six 1-week
      periods, started on 6 February and continued until 20 March. Flushing was
      performed by restricted feeding in periods 2 and 3 and refeeding in periods 4 and
      5. The animals were weighted weekly and blood sampled at the end of periods 1, 2
      and 4, 1 week after changes in the food supply of the FLUSH group. Plasma was
      analysed for insulin, insulin-like growth factor-1, total triiodothyronine, total
      thyroxine, free thyroxine, glucose and fructosamine. Generally, within the FLUSH
      group, animal live weights and blood metabolites were strongly influenced by
      energy supply, these variables remained almost constant in the CON group. In the
      NEG group the live weight, total triiodothyronine, total thyroxine, insulin and
      glucose concentrations decreased significantly. Differences in blood metabolites
      between the FLUSH and CON groups were non-significant, reflecting only small
      differences when considered over the total experimental period, thus reflecting
      an acute response to a varied energy supply, while the differences between the
      NEG group and the CON and FLUSH groups were significant, indicating a
      considerable chronic response in all metabolites to a constantly low energy
      supply.

PMID- 9606754
TI  - Non-isotopic detection of nucleolar transcription in pre-implantation mouse
      embryos.
AB  - Nucleolar transcription was analysed in permeabilized pre-implantation mouse
      embryos at the four-cell, eight-cell, morula and early blastocyst stages using
      confocal microscopy to detect incorporated 5-bromouridine. The results
      demonstrated that the patterns of nucleolar transcription sites were common for
      all embryonic stages studied. They consisted most frequently of tightly
      associated groups of transcription foci similar to those encountered in somatic
      interphase cells. In addition, the nucleologenesis accompanying each cell cycle
      apparently gave rise to a different fluorescent pattern, that is to spatially
      separated fluorescent foci in the cells just after the resumption of rRNA
      synthesis. An immunoelectron microscopic analysis of the nucleolar transcription
      was also performed in the eight-cell embryos. A signal, usually consisting of
      clustered gold particles, was found specifically within nucleolar dense fibrillar
      components. This result was in agreement with established findings, which
      identify dense fibrillar component as the major site of nucleolar transcription
      in somatic cells.

PMID- 9606755
TI  - The arthritogenic properties of microbial antigens. Their implications in disease
      states.
AB  - The sharing of antigenic determinants between host and microbe is a common event
      and new microbial-tissue cross-reactions are being recognized each year. Almost
      every human organ has been implicated as a possible target. The purpose of this
      article is to examine the arthritogenic properties of these microbial antigens
      and to explore the mechanisms by which they induce pathologic damage and disease.

PMID- 9606756
TI  - The polymerase chain reaction in infectious and post-infectious arthritis. A
      review.
AB  - Polymerase chain reaction and other DNA amplification techniques to identify
      elusive infections should prove to be an effective tool for the clinical and
      investigative rheumatologist. The capability to identify and characterize
      infectious organisms in fluids and tissue will enable early, specific, and
      potentially curative treatment. Similarly, the capability to exclude infection
      and differentiate postinfectious diseases will enable other therapies to control
      the inflammation. Understanding these molecular techniques will most certainly
      improve clinicians' effectiveness for diagnosis and care.

PMID- 9606757
TI  - Rheumatic fever. The relationships between host, microbe, and genetics.
AB  - Acute rheumatic fever is a delayed, nonsuppurative sequela of a pharyngeal
      infection with the group A streptococcus. The onset of the disease is usually
      characterized by an acute febrile illness; however, there may be chronic
      involvement of the heart and/or central nervous system. The article explores the
      relationship between the initial infection and host-microbial interactions that
      may be operative in disease pathogenesis.

PMID- 9606758
TI  - Reactive arthritis.
AB  - Concepts about reactive arthritis are changing and must embrace consideration of
      the fact that bacteria or their products are present in the joint, not just at
      the portal of entry in the gastrointestinal (GI) or genitourinary (GU) tracts.
      With chlamydia-associated disease, atypical elementary bodies can be seen in
      synovium by electron microscopy, and nucleic acids, including RNA, can be found.
      It is not yet clear if bacterial nucleic acids are present in postenteric
      reactive arthritis and whether disease courses are predictably different after GI
      or GU infection. How bacteria are disseminated to joints and local factors,
      including cytokines that influence their persistence, are under study. Treatment
      with antibiotics may help some chlamydia-associated reactive arthritis but is not
      invariably effective.

PMID- 9606759
TI  - Orthopedic management of septic arthritis.
AB  - The goals in the management of septic arthritis are joint decompression, joint
      sterilization, and preservation of joint function. Opinions on how these goals
      are best accomplished vary among medical disciplines. Although the literature
      supports both serial aspirations and arthrotomy as viable ways to treat
      pyarthrosis, most orthopedic surgeons prefer arthrotomy. There are advantages to
      surgical management, including more complete decompression, especially in
      infections characterized by thick, purulent fluid or loculations; a lower intra
      articular bacterial count after lavage; the opportunity to perform a synovectomy;
      and no delay in cases that may be unresponsive to simple aspiration and
      antibiotics. Rehabilitation of the septic joint is paramount in preserving range
      of-motion and cartilage protection. Although splinting and immobilization are
      necessary in treating acute infections, early range of motion is paramount in
      preserving long-term joint function.

PMID- 9606760
TI  - Septic arthritis in children.
AB  - Because of its seriousness, septic arthritis should be considered early in the
      differential diagnosis of any child presenting with joint inflammation.
      Physicians who care for children should be aware of the early signs and symptoms
      of septic arthritis and be aggressive about establishing the diagnosis so that
      treatment is not delayed. Early orthopedic consultation and a low threshold for
      performing arthrocentesis are prudent. Prolonged and appropriate antimicrobial
      therapy is warranted to achieve optimal results.

PMID- 9606761
TI  - Gonococcal arthritis.
AB  - Disseminated gonococcal infection is the most common systemic complication of
      acute gonorrhea and occurs in 0.5% to 3.0% of patients with untreated mucosal
      infection. It is also the most common cause of septic arthritis in patients less
      than 30 years of age. Fortunately, the incidence of gonorrhea is decreasing
      dramatically in the United States and Western Europe, although it is still high
      in developing countries. Increasing resistance to antibiotics requires continuous
      surveillance of antimicrobial susceptibilities to determine the efficacy of
      current therapeutic measures.

PMID- 9606762
TI  - Musculoskeletal manifestations of Lyme arthritis.
AB  - Lyme disease is a treatable and curable infectious disease that can be diagnosed
      with relative confidence with attention to the details of the syndrome and proper
      use of serologic testing to confirm the clinical diagnosis. Lyme disease should
      not be a "diagnosis of exclusion," made on the basis of isolated serologic
      reactivity or because of the presence of symptoms compatible with Lyme disease.
      The pathogenesis of chronic complaints following infection with B. burgdorferi is
      often unclear, but such persistent complaints should not automatically be
      ascribed to ongoing infection. There is no proven role for long-term antibiotics
      or combination regimens.

PMID- 9606763
TI  - Hepatitis C-associated autoimmune disorders.
AB  - Hepatitis C virus (HCV) infection has been associated with multiple autoimmune
      manifestations. The immune response to HCV infection encompasses the development
      of autoantibodies, immune complex formation and deposition, and cryoglobulinemia
      complicated by vasculitis, glomerulonephritis, or neuropathy. HCV infection has
      been associated with antiphospholipid antibody syndrome, RA, SLE, PM/DM, and
      thyroid disease. HCV-infected patients also have a high incidence of sicca
      symptoms with sialoadenitis, and reports of low-grade lymphoproliferative
      malignancies have emerged. Optimal treatment for HCV-related autoimmune disease
      remains to be determined, but patients seem to respond to immunosuppression with
      classic agents or interferon.

PMID- 9606764
TI  - Rheumatic manifestations of parvovirus B19 infection.
AB  - Human parvovirus B19 is an emerging DNA virus. B19 infection is common and
      widespread. Major manifestations of B19 infection are transient aplastic crisis,
      erythema infectiosum, hydrops fetalis, acute and chronic rheumatoid-like
      arthropathy, and, in the immunocompromised host, chronic or recurrent bone marrow
      suppression. A number of less common manifestations of B19 infection include
      various rash illnesses, neuropathies, and acute fulminant liver failure. Of
      rheumatologic interest, B19 infection must be differentiated from early
      presentation of more classic erosive rheumatoid arthritis and, in some cases,
      systemic lupus erythematosus. It is unlikely that B19 plays a role in classic
      erosive rheumatoid arthritis, but understanding pathogenesis of B19 arthropathy
      may provide insights into the mechanisms by which rheumatoid arthritis develops.
      Evidence for persistence of B19 infection suggests that human parvovirus B19
      infection may serve as a model for the study of virus-host interactions and the
      role of viruses in the pathogenesis of rheumatic diseases.

PMID- 9606765
TI  - HIV infection-associated inflammatory musculoskeletal disorders.
AB  - Inflammatory musculoskeletal complaints are relatively common during the course
      of HIV infection, although they tend to be more frequent during late stages. The
      clinical spectrum is varied, ranging from arthralgias to distinct rheumatic
      disorders, such as Reiter's syndrome and psoriatic arthritis. The therapeutic
      management often poses a challenge, although most patients respond to
      conventional first- and second-line anti-inflammatory medications.

PMID- 9606766
TI  - Infection in systemic lupus erythematosus.
AB  - The improved survival of SLE patients since the 1950s is the result of not only
      better treatment, but also supportive treatment of renal failure and the wealth
      of antibiotics now available. Ironically, the wider use of immunosuppressives,
      especially the alkylating drugs, and the longer survival of patients with renal
      insufficiency and renal failure have made the identification and appropriate
      treatment of infection in SLE an ongoing challenge.

PMID- 9606767
TI  - Muscle fatigue in a standing heel-rise test.
AB  - The fatigue process of the triceps surae was evaluated during a standing heel
      rise test, comprising of eccentric and concentric muscle actions. Ten healthy
      women with a mean age of 24 years participated. The heel-rise test was performed
      until exhaustion. Work and electromyographic activity expressed as root mean
      square and mean power frequency of the gastrocnemius and soleus muscles were
      calculated. The average number of heel-rises performed was 25 +/- 1. Work
      decreased significantly during the test. Mean power frequency decreased
      significantly in both phases. During the eccentric phase the decrease was
      significantly larger in the gastrocnemius than in the soleus muscle. There were
      no significant changes in root mean square except for a decrease in the soleus
      muscle during the eccentric phase. The present results, showing different fatigue
      patterns in the two muscles, could be used as reference when testing the fatigue
      process in different clinical conditions. Recommendations for standardization of
      a heel-rise test are given.

PMID- 9606768
TI  - The standing heel-rise test in patients with upper motor neuron lesion due to
      stroke.
AB  - The objective was to investigate the fatigue process in the triceps surae during
      the heel-rise test (eccentric and concentric phases) in comparison with a walking
      test and muscle strength. Eight men with prior stroke and 8 age-matched healthy
      men participated. The electromyographic activity in form of root mean square and
      mean power frequency of the gastrocnemius and soleus muscles were measured and
      work estimated. Walking speed and maximal peak torque were measured and differed
      significantly between the patient and reference groups. There were no significant
      differences between the groups nor legs concerning the number of heel-rises or
      work performed. In the eccentric phase, mean power frequency decreased
      significantly more in the gastrocnemius than in the soleus muscle in the
      reference group, while mean power frequency in the soleus muscle tended to
      decrease more, though non-significantly, in the affected leg. The conclusion is
      that the capacity to perform the heel-rise test in patients with prior stroke is
      better than plantarflexor peak torque and walking speed.

PMID- 9606769
TI  - Sit-to-stand manoeuvre in hemiparetic patients before and after a 4-week
      rehabilitation programme.
AB  - The objective of the study was to document the sit-to-stand of 35 moderately
      affected hemiparetic patients before and after a 4-week inpatient rehabilitation
      programme and to investigate the influence of the side of hemiparesis and
      impaired proprioception on its outcome. The therapists trained the patients to
      distribute equal weight on both legs and to avoid lateral compensatory tilt of
      the trunk. The body weight distribution and the displacement of the centre of
      mass in the frontal plane were studied by assessment of triaxial ground reaction
      forces. Symmetrical weight acceptance and minimal lateral sway were not reached
      during the 4-week rehabilitation, with the exception of the patients with a left
      hemiparesis (n = 19) and no proprioceptive deficit (n = 18).

PMID- 9606770
TI  - Effects of day-hospital rehabilitation in stroke patients: a review of randomized
      clinical trials.
AB  - The purpose of this study was to review the literature on the effects of day
      hospital rehabilitation (DHR) in stroke patients. In The Netherlands DHR concerns
      a multidisciplinary approach to decrease disability and handicap and to optimize
      quality of life in an outpatient setting. Data were collected by a computer-aided
      search of published randomized trials. Fifteen articles reporting on seven
      randomized controlled trials were selected. Data extraction included a score for
      quality of the methods, based on four categories: "study population",
      "interventions", "effects" and "data presentation and analysis". To each
      criterion a weight was attached and the maximum score was set at 100 points. In
      judging the methodological quality of the selected studies, one study proved
      insufficient. Of the remaining studies the sum score varied from 34 to 67, with a
      mean of 50. Comparison of the results of the studies is complicated by different
      definitions of DHR, different natures of the control group and the study
      population, and the variety of measurement instruments applied. Often instruments
      were applied whose reliability and validity was not proven. As of now it is not
      possible to prove that DHR for stroke patients is effective. In future research a
      standardized definition of DHR, a uniform control group, and acceptable research
      methodology and adequate measurement instruments must be applied.

PMID- 9606771
TI  - Stimulation with low frequency (1.7 Hz) transcutaneous electric nerve stimulation
      (low-tens) increases motor function of the post-stroke paretic arm.
AB  - The object of this study is to determine if the functional motor capacity of the
      paretic extremity can be improved by stimulation with low intensity low frequency
      (1.7 Hz) transcutaneous electric nerve stimulation (Low-TENS), started 6-12
      months after a stroke. Forty-four patients who had a paretic arm as a consequence
      of their first stroke were included and randomly assigned to either a treatment
      group (n = 26) or a control group (n = 18). Patients in both groups received
      physiotherapy at a day-care center, usually twice a week. The treatment group
      received, in addition, Low-TENS for 60 min, five days a week for three months.
      Results showed that motor function increased significantly in the treatment
      group, compared to controls. The Low-TENS did not decrease either pain or
      spasticity. It is concluded that stimulation by means of Low-TENS could be a
      valuable complement to the usual training of arm and hand function in the
      rehabilitation of stroke patients.

PMID- 9606772
TI  - We can cure your child's clumsiness! A review of intervention methods.
AB  - Intervention procedures for treatment of clumsiness have come in many guises. We
      have looked at some of the most powerful methods put forward in the past 30 years
      -Perceptual-motor training (PMT), Sensory Integration Therapy (SIT), and some
      promising new approaches. Both the PMT and the SIT have been heavily criticised.
      It is hard to find support for the idea that the programmes improve academic
      skills or that they have more than a limited effect on perceptual-motor
      development as claimed. The more recently introduced Kinaesthetic training is
      shown to have an effect on general motor competence but that this may be better
      explained in terms of the general principles on which this training procedure
      lies rather than the influence on Kinaesthesis per se. Since other recent studies
      have also shown a dependence on similar general principles, it might be asked
      whether it is the teacher rather than the programmes that accounts for the
      differences shown between different intervention programmes.

PMID- 9606773
TI  - A submaximal back extension endurance test utilising subjective perception of low
      back fatigue.
AB  - The present study was designed to evaluate the diagnostic value of a new
      submaximal back extension endurance test in the classification between patients
      with non-specific chronic/recurrent low back trouble (LBT) and controls. The back
      pain questionnaires included pain duration, intensity, regularity and the Pain &
      Disability Index. The subjects performed dynamic back extensions on a specially
      designed measurement and training unit at a fixed repetition rate with a load
      that was based on the subject's estimated upper body mass. The degree of
      perceived fatigue (unmodified Borg scale, 6-20) was inquired in 15 second
      intervals throughout the protocol and the slope (change/minute) was calculated.
      The Borg scale slope increased faster and the score at the end of the test was
      higher in the LBT group than in the control group during the test. Receiver
      operating characteristics analysis revealed significant diagnostic value for the
      Borg scale slope (0.74) and for the Borg scale at the end of the test (0.70). We
      conclude that LBT patients experience fatigue faster than controls during a
      repetitive submaximal back extension task. The test may offer a low-risk, low
      cost evaluation method for assessing the severity of LBT when combined with other
      relevant clinical data.

PMID- 9606774
TI  - On the reliability and usefulness of methods for grip strength measurement.
AB  - The purposes of this investigation were to assess the accuracy of a grip strength
      measuring instrument, the Grippit, to modify previously developed methods for
      measuring maximal isometric grip strength (12) and to evaluate the reliability of
      these methods, with the use of the Grippit. Grip strength during short (maximal
      voluntary isometric strength, MVC) and sustained (SMVC) contractions was
      measured. The modifications concerned the definitions of MVC and SMVC, the
      measuring position, the intervals between trials and sessions, and the recording
      procedure. The intra-observer reliability study comprised 29 healthy subjects,
      and the inter-observer study 10 other healthy subjects. The Grippit had very high
      precision. The intra-observer reliabilities of MVC and SMVC measurements were
      improved compared to those with the previous methods (12). The inter-observer
      reliability was very high.

PMID- 9606775
TI  - Associations of sensory-motor functions with poor mobility in 75- and 80-year-old
      people.
AB  - This study investigated the associations of sensory-motor functions with mobility
      in elderly people. All 75- and 80-year-old residents of the city of Jyvaskyla,
      Finland, were invited to take part in the study. A total of 617 (93%) persons
      were interviewed, and 500 (75%) took part in laboratory examinations. Self
      reported mobility was recorded during the interview. Basic mobility functions
      (maximal walking speed and stair-mounting ability) and sensory-motor functions
      (maximal isometric muscle strength, standing balance, reaction time and visual
      acuity) were measured in the laboratory. Multivariate analyses showed that poor
      sensory-motor functions were significantly associated with poor performance in
      basic mobility functions and that poor performance in basic mobility functions
      was associated with self-reported disability in mobility. The associations
      discovered were consistent with models of the disablement process. Muscle
      strength, balance, reaction time and vision all have individual significance for
      mobility, underlining the need for multifactorial approaches in prevention and
      rehabilitation.

PMID- 9606777
TI  - Ureteroscopic holmium lasertripsy for ureteric stones. Initial experience.
AB  - The clinic benefits of the Holmium: YAG laser include a pronounced haemostatic
      effect, fibreoptic delivery system and a wide range of power-setting options. We
      review our initial experience in treating 48 patients with ureteric stones.
      Stones were located in the upper, middle and lower ureter in 27%, 21% and 52% of
      patients respectively. The Holmium laser successfully fragmented all calculi and
      there were no major complications. We have found the Holmium laser to be a safe,
      effective and reliable alternative for the management of urolithiasis.

PMID- 9606776
TI  - Can duplex Doppler ultrasound replace computerized tomography in staging patients
      with renal cell carcinoma?
AB  - The purpose of this study was to evaluate the accuracy and reliability of duplex
      Doppler ultrasound (US) and computerized tomography (CT) in staging patients with
      renal cell carcinoma (RCC). Sixty-six patients were evaluated pre-operatively
      with duplex Doppler ultrasound and CT. The results were compared with the
      surgical and histopathological findings. T stage was determined correctly with
      duplex Doppler US and CT in 56 and 50 cases respectively. In 4 patients with
      nodal disease duplex Doppler US was correct in 2 patients, 1 was false positive.
      With CT, 3 patients were staged correctly and 3 were false positive. Of the 14
      patients with vascular tumour thrombi, 13 were staged correctly with duplex
      Doppler US and 12 with CT scan. False positive vascular tumour invasion was seen
      only with CT in 4 cases. Based on these results we conclude that duplex Doppler
      US is at least as accurate as CT scanning in the staging of RCC. Also in patients
      with renal or caval thrombi, duplex Doppler US is highly accurate in establishing
      the diagnosis and in the determination of the extent of the thrombus.

PMID- 9606778
TI  - Urodynamic predictors of upper tract deterioration in children with
      myelodysplasia.
AB  - The clinical and urodynamic data of 62 children with myelodysplasia without
      previous urological treatment were tested statistically for the ability to
      predict upper tract deterioration. This was done by comparing these data among 26
      children with dilated upper tracts and 36 children with normal upper tracts.
      Vesicoureteric reflux had a strong positive correlation with upper tract dilation
      but the maximum cystometric capacity, detrusor instability, compliance, maximum
      urethral closure pressure and peak flow rate all had no predictive value.
      Residual urine is sensitive and negatively predictive and leak pressure is
      specific and positively predictive; detrusor pressure at peak flow, opening
      pressure, pressure at least flow and the detrusor-adjusted mean passive urethral
      resistance relation factor (DAMPF) are sensitive and specific with high positive
      and negative predictive values.

PMID- 9606779
TI  - Bladder diverticulectomy: operative technique.
AB  - We present a simple technique of bladder diverticulectomy. Etiology,
      pathogenesis, diagnosis, and treatment of bladder diverticula are discussed. We
      recommend this technique for common use, since it is safe and time-saving.

PMID- 9606780
TI  - Antiemetic efficacy of prednisolone: a placebo-controlled trial in patients with
      advanced prostatic cancer treated with estramustine phosphate.
AB  - The antiemetic effect of prednisolone on nausea/vomiting was investigated in 67
      patients with advanced prostatic cancer and a performance status of < or = 2. The
      study was a double-blind, placebo-controlled, randomized trial with a parallel
      group design. The objective was to compare the incidence and severity of
      nausea/vomiting between the two groups. Prednisolone or placebo was given twice
      daily for 3 weeks with the dose decreased during the third week from 15 mg/day to
      10 mg for 3 days and finally to 5 mg/day during the last 4 days. EMP was given as
      two 140 mg capsules daily for 3 days at the beginning, then as four capsules for
      4 days followed by six capsules for 21 days. Areas under curves (AUCs) for nausea
      and for nausea/vomiting scores were calculated based on the patient's diary
      notes: nausea (0-3), vomiting (0-6), nausea/vomiting (0-9). Control of emesis in
      terms of complete, moderate or poor control was registered. Pretreatment
      characteristics were evenly balanced. The results indicated that no statistical
      differences between the two groups of patients were present in AUCs for weeks 1-3
      or weeks 1-4. We conclude that it was not possible to demonstrate a significant
      antiemetic efficacy of prednisolone. However, in all but one case the patients in
      the prednisolone group could be treated for at least 3 weeks without any major
      incidents of nausea/vomiting.

PMID- 9606781
TI  - Evaluation of needle biopsy in the diagnosis of prostatic carcinoma in men with
      prostatic intraepithelial neoplasia.
AB  - Prostatic intraepithelial neoplasia (PIN) is considered a premalignant lesion of
      the prostate. It is often encountered in prostate needle biopsy in cases where no
      cancer is identified. In order to evaluate its importance 25 patients with PIN in
      a former prostate needle biopsy underwent a second ultrasound guided needle
      biopsy. The first biopsy was performed in all patients as a result of positive
      DRE. In 13 patients (52%), prostate cancer was identified in the second specimen.
      All presented with high or intermediate grade PIN in the first biopsy. PSA values
      were compared with PIN grade and cancer presentation in the second biopsy,
      although no statistically significant difference was proven. In conclusion, when
      PIN is discovered in prostate needle biopsy in patients with positive DRE, a
      second biopsy has to be performed in order to exclude the possibility of a
      prostate carcinoma.

PMID- 9606782
TI  - Value of sextant biopsies in the assessment of local cure following external beam
      radiotherapy of prostatic adenocarcinoma.
AB  - Between 1982 and 1992, 73 patients received radical external beam radiotherapy
      (EBR) for prostatic adenocarcinoma at the Central Hospital, Vasteras, with an
      average dose of 68.1 Gy (range 64.5-72.5 Gy) and an average cumulative radiation
      effect (CRE) of 18.2 (range 17.1-19.9) All patients had a negative bone scan
      prior to treatment and presented with clinical stage T1-T4,Nx,Mo. Twenty-four out
      of 36 surviving patients consented to participate in a follow-up study which
      included transrectal, ultrasonically guided prostate biopsies. The average follow
      up from EBR to biopsy was 5.5 years (range 3.6-11.1 years). Sixteen (67%) of the
      patients had a positive biopsy. The average PSA level in the biopsy-positive
      group was 35.7 ng/mL (range 3.9-200 ng/mL). In the biopsy-negative group, the
      average PSA was 3.7 ng/mL (range 0.2-13.0 ng/mL). The conclusion is that the
      degree of local cure achieved in patients with prostatic cancer treated with
      external beam radiotherapy is low (33%), and that a higher radiation dose may be
      required to eradicate this malignancy.

PMID- 9606783
TI  - Lymphangiography combined with biopsy and computer tomography to detect lymph
      node metastases in localized prostate cancer.
AB  - To evaluate the efficacy of lymphangiography combined with fine needle aspiration
      biopsy and computer tomography (CT) for lymph node staging in clinically
      localized prostate cancer. Prospective evaluation of nodal involvement was
      carried out using standard bipedal lymphangiography combined with fine needle
      aspiration biopsy (FNAB) in 70 patients (aged 47 to 75 years, mean age 63 years)
      with apparently locally confined prostate cancer before intended radical
      prostatectomy. Sixty-four patients also underwent computer tomography. Seventeen
      withdrew the decision to undergo a radical prostatectomy, leaving 53 patients
      with pathologic examination of the lymph nodes eligible for analysis. Lymph node
      metastases were diagnosed in 8 patients (8/53 = 15.1%). Three were diagnosed
      preoperatively by FNAB, 3 peroperatively by lymph node dissection and frozen
      section biopsy and an additional 2 at the final pathologic assessment. The
      sensitivity, specificity, positive and negative predictive values for
      lymphangiography and lymphangiography combined with FNAB in predicting nodal
      disease, based on the analysis of the 53 patients with known pathologic results,
      were 0.63, 0.76, 0.31, 0.92 and 0.38, 1.00, 1.00, 0.90, respectively. The
      corresponding values for CT staging were 0.25, 0.98, 0.67 and 0.87, respectively.
      The efficacy of bipedal lymphangiography alone or combined with FNAB or CT alone
      for assessment of nodal metastases is too low to be worthwhile for lymph node
      staging in localized prostate cancer patients with expected low or intermediate
      probability of nodal disease.

PMID- 9606784
TI  - Risk of haemorrhage from transurethral prostatectomy in acetylsalicylic acid and
      NSAID-treated patients.
AB  - Postoperative bleeding in patients who regularly ingest acetylsalicylic acid
      (ASA) has been reported after several types of surgery. However, data on the
      influence of ASA on the risk of haemorrhage from transurethral prostatectomy (TUR
      P) have been conflicting. We have studied retrospectively the unselected clinical
      records of all patients undergoing TUR-P in the Department of Urology at Hvidovre
      Hospital (during 1992-1994) with special focus on the use of ASA and non
      steroidal anti-inflammatory drugs (NSAIDs). In total, 457 records were examined:
      99 patients on ASA/NSAID received 42 units of blood, while 358 patients free from
      such medication received 68 units of blood, a significantly smaller amount (p =
      0.0390). We conclude that ASA and NSAIDs increase the risk of bleeding during and
      after TUR-P, and we recommend the withdrawal of these drugs for one week before
      TUR-P.

PMID- 9606785
TI  - Transurethral electrovaporization of the prostate in benign prostatic
      hyperplasia. Evaluation of results using different urodynamic parameters.
AB  - We studied the obstruction-relieving capabilities of transurethral
      electrovaporization of the prostate (TVP) in 32 symptomatic patients with benign
      prostatic hyperplasia (BPH). Urodynamic studies with pressure-flow analysis were
      performed before and 6 months after treatment. All 32 patients showed significant
      improvement of both subjective and objective obstruction parameters. There were
      few postoperative irritative symptoms and one patient required recatheterization.
      In conclusion, TVP is a promising modification of performing transurethral
      resection of the prostate, and it is indeed capable of relieving bladder outflow
      obstruction.

PMID- 9606786
TI  - Risk factors in haemodialysis patients: evaluation of commonly measured variables
      on death rate.
AB  - This study evaluates risk factors among commonly measured laboratory values and
      clinical findings in haemodialysis patients, followed by attempts to identify
      optimal treatment strategies. Average plasma concentrations of albumin, protein,
      CO2, urea and creatinine, and average values of systolic and diastolic blood
      pressure, together with information on gender, age and renal diagnosis, were
      related to survival rate in 210 sequences of haemodialysis treatment during a
      period of 94 months. The average treatment time was 12.6 months (range 1-94). The
      material was analysed with stepwise regression analysis using the Cox
      proportional hazard model (BMDP 2L), and actuarial life table analysis was
      performed to illustrate the magnitude of influence of the independent variables
      on patient survival (BMDP IL). Patient survival was negatively correlated with
      age and positively correlated with average plasma concentrations of albumin.
      Surprisingly, patient survival was negatively correlated with plasma CO2. Patient
      survival was significantly lower in diabetics.

PMID- 9606787
TI  - Osmoregulatory function of the kidney in enuretic children.
AB  - Twenty children with primary nocturnal enuresis and 20 healthy children of the
      same age and sex were studied. Natural urination was used for the 24-h urine
      collection. It was found that urine osmolality and free water reabsorption during
      the night did not differ statistically significantly between the enuretic
      children and the healthy. The increased diuresis in the enuretic children was
      caused by a higher excretion of the osmotically active solutes, including sodium.
      Use of desmopressin reduced diuresis and natriuresis to normal levels. It is
      suggested that the main role in the pathogenesis of the studied form of nocturnal
      enuresis is played by a decrease in ion reabsorption, probably in the thick
      ascending Henle loop, which facilitates the increase in diuresis and occurrence
      of nocturnal enuresis.

PMID- 9606788
TI  - Scrotal involvement in Henoch-Schonlein purpura in children.
AB  - Different rates of scrotal involvement in Henoch-Schonlein purpura (HSP) have
      been reported. We assessed scrotal involvement in 86 children over a 20-year
      period: 10 patients suffered from scrotal involvement and 9 of them also had
      arthritis. The possible association between scrotal involvement and arthritis may
      help the physician in the differential diagnosis of atypical presentations.

PMID- 9606789
TI  - Adrenal cortical carcinoma associated with a splenic vein tumor thrombus.
AB  - A unique case is reported of a left adrenal cortical carcinoma with a splenic
      vein tumor thrombus. En bloc radical nephroadrenalectomy, distal pancreatectomy,
      splenectomy and splenic vein tumor thrombectomy were performed. Reconstruction of
      the proximal portal vein was required, incorporating a segment of the left renal
      vein (harvested from the surgical specimen) as a free interposition graft,
      bridging the defect between the superior mesenteric vein and portal vein. To our
      knowledge, this is the first reported case of an adrenal cortical carcinoma
      associated with a splenic vein tumor thrombus. In addition, the described
      technique used to reconstruct the proximal portion of the portal vein has not
      been previously reported.

PMID- 9606791
TI  - Infected scrotal epidermoid cyst mimicking a sclerosing lipoglanuloma and
      extending to the gluteal region.
AB  - Although scrotal masses are not uncommon, a lesion in this site extending to the
      gluteal lesion is exceptionally rare. We encountered a large epidermoid cyst
      mimicking a sclerosing lipogranuloma of the scrotum.

PMID- 9606790
TI  - Endovascular embolization of a renal artery aneurysm using interlocking
      detachable coils.
AB  - A 51-year-old woman with a renal artery aneurysm was successfully treated with
      endovascular embolization using interlocking detachable coils. The parent vessel
      was spared, leading to preservation of the uninvolved portion of the kidney.

PMID- 9606792
TI  - Lycopodium spores in transrectal ultrasound-guided core biopsies of the prostate.
AB  - Lycopodium clavatum (LC) spores were found in two cases in transrectal ultrasound
      guided core biopsies of the prostate. The source turned out to be the coating of
      the condoms used for protection of the ultrasound probe. To minimize confusion in
      analyzing the biopsies and to avoid granulomas of the prostate, LC spore-free
      condoms are available and are recommended for the biopsy procedure.

PMID- 9606793
TI  - New drainage technique in the ureteropelvic junction obstructions. Side-to-side
      ureterocalicostomy (or ureterocaliceal by-pass) preserving renal pelvis and
      ureteropelvic junction.
AB  - We present a new ureterocalicostomy technique in a patient with intrarenal pelvis
      together with renal artery compression on the pelvis and ureteropelvic junction
      (UPJ). The patient had grade 4 hydronephrosis in the left kidney and angulation
      at the ureteropelvic junction. We performed side-to-side ureterocalicostomy
      between the ureter and lower calyx of the kidney.

PMID- 9606794
TI  - Hibernoma of the spermatic cord. The second reported case and literature review.
AB  - A 23-year-old man was admitted with a 6-month history of a slow-growing mass in
      the left side of the scrotum. Echography revealed a mixed-density mass that was
      mainly fatty. The histopathological examination was considered typical of a
      hibernoma. To our knowledge this is the second case reported.

PMID- 9606795
TI  - Orthotopic bladder substitution in a presacral ectopic kidney bearer.
AB  - Orthotopic bladder substitution after radical cystectomy may require original
      surgical procedures when urinary tract malformations are present. A case of
      presacral left ectopic kidney with hypoplastic ureters is described, and the main
      issues faced in lower urinary tract reconstruction are pointed out.

PMID- 9606796
TI  - [Medical research without genetic technology?].

PMID- 9606797
TI  - [Genetic technology and the thorn of ambivalence].
AB  - The following article reflects on the relationship between man and the world. The
      world not only surrounds man, but man participates in it. This participation has
      various implications for research and the application of genetic engineering. The
      article focuses on man's restricted capacity to know and foresee all the
      consequences of his actions and his ambivalence for good and bad. Man must be
      aware of his own limits and show due concern for mankind and the world.

PMID- 9606798
TI  - [The prognosis of premature infants: from the viewpoint of gynecologists
      obstetricians and results from Lausanne].
AB  - AIM OF THE STUDY: To assess the views of obstetricians concerning the survival
      rate in neonates on the basis of gestational age and birth-weight, rate of severe
      handicap, and minimum gestational age for preventive and curative measures
      (steroids for foetal lung maturation and caesarean section in the event of acute
      foetal distress). Then, to compare these results with the outcomes observed in
      the referral centre for these obstetricians. METHOD: We circulated an anonymous
      questionnaire (two mailings between October 1995 and February 1996) to
      obstetricians in the Lausanne area. The replies were compared with prospective
      data from the Lausanne obstetric unit (1989-1995) and neonatal intensive care
      unit (1982-1993) backed by the neurodevelopmental outcome assessed by regular
      follow-up until the age of 8 1/2 years. RESULTS: We obtained 116 replies from the
      270 specialists questioned (43% participation). The mortality rates in Lausanne
      are described by gestational age and birthweight, as is the rate of severe
      handicap. We observed significant overestimation of the mortality rate for
      premature infants between 25 and 31 weeks and for birthweights over 600 grams.
      The rate of severe handicap was widely overestimated for a gestational age below
      28 weeks at delivery or a birthweight below 1500 g (prognosis 31.2% and 21.5%
      respectively, compared with actual figures of 7.4% and 6.8%). Moreover,
      distribution of replies showed marked heterogeneity between 26 and 29 weeks and
      between 600 and 1000 grams. The estimated minimum gestational age was 26 weeks
      (mean) for starting steroid therapy and 27 weeks for caesarean section for acute
      foetal distress. CONCLUSION: Assessment of prognosis by obstetricians did not
      correlate with our results and reflected the disparity of data found in the
      literature. Nevertheless, the implications of this discrepancy may be slight. The
      study stresses the efficacy of the regionalisation of perinatal care in the
      Lausanne area, where we observed only 6% of outborn weighting less than 1500
      grams in the 18 maternity departments covered. The rate of completed antenatal
      steroid therapy (41% for infants below 1500 grams) appears to be favourable in
      our population compared with the literature. We advocate permanent information on
      local results regarding perinatal outcome, to enable individual obstetricians to
      consider the desirability of treating, transferring or even counselling or
      reassuring their patients.

PMID- 9606799
TI  - [The value of screening serology in anti-hepatitis A vaccination of travelers].
AB  - To select the travellers most likely to benefit from anti-hepatitis A (HA)
      antibody testing, the following criteria have been proposed: (A) being born
      before 1945, (B) a stay over 1 year in a developing country or (C) a history of
      jaundice. We present a prospective study to assess the practical use of these
      criteria. Following a recent survey in the general population of Lausanne showing
      HA seroprevalence of 52.6% in the age group over 45, we included an A1 criterion
      (A extended to birth before 1950). Anti-HA IgG testing and a questionnaire were
      proposed to all travellers presenting one or more criteria. RESULTS: Out of 1187
      consecutive travellers, 176 (14.8%) had one or more criteria (219 [18.5%] when A1
      was used). Criteria A applied to 8.5% of all travellers, A1 to 13.8%, B to 6.3%
      and C to 3.1%. Only 3% of travellers had more than one criterion. Overall
      seroprevalence among the selected group was 48.3%. Seroprevalence of travellers
      below 60 years old was under 30%, unless a second criterion was present in which
      case seroprevalence was 10% higher. Eighty percent of travellers with a history
      of jaundice were found to be positive. The use of the recommended criteria spared
      94 travellers (46.3% of those tested and 7.9% of all travellers) unnecessary
      immunisation. Among travellers older than 60 years, a 30% economy on the total
      sum for immunising all of them, without any prior testing was realised.
      CONCLUSIONS: Among the population of travelers consulting our travel clinic, the
      seroprevalence for HA is lower than in the general population. We recommend that
      testing should be proposed only to travellers aged over 60, or with a history of
      jaundice, or to those with a combination of 2 out of 3 criteria.

PMID- 9606800
TI  - Testing for HIV infection in time: scientific reasons.
AB  - The author advocates testing, diagnosis and therapy of HIV infection as soon as
      possible after contracting the virus and whenever feasible. The arguments are
      deduced from the results of basic research. The following should be reduced,
      delayed or inhibited: (1) the viral load in blood plasma and semen; (2) rapid
      internal propagation of the virus, which is combined with integration of
      proviruses into cells of unknown life span and compartmentalisation (e.g. the
      brain may present a sanctuary site); (3) rapid individual formation of
      quasispecies out of initially homogeneous virus strains of suboptimal fitness,
      combined with the transition of NSI strains to the more aggressive SI strains and
      escape from the immune response and therapy; (4) irreversible damage to the
      immune system; later opportunistic infections; (5) unconscious transmission of
      possibly drug-resistant virus. Early diagnosis and therapy appear possible in
      many cases, involving major advantages for individuals and society.

PMID- 9606801
TI  - Extrapulmonary inflammatory myofibroblastic tumor: a clinical and pathological
      survey.
AB  - Inflammatory myofibroblastic tumor (IMT) or inflammatory pseudotumor was
      initially recognized in the lung, and somewhat later, a similar-appearing
      pathological process was reported in the liver. Presently, this tumor has been
      described in virtually all major organs and extrapulmonary sites with a few
      exceptions. It was thought initially that the IMT was nonneoplastic and
      represented an aberrant inflammatory response despite its gross and microscopic
      features of a spindle cell neoplasm. The inflammatory hypothesis about the
      pathogenesis has been more readily accommodated in the lung than in the
      extrapulmonary sites of involvement. Some cases, however, were accompanied by the
      constitutional symptoms and signs of an inflammatory process, which resolved in
      most cases after surgical resection. There were some pathological aspects of the
      IMT that seemingly contradicted its purely inflammatory nature, including its
      potential for local recurrence; development of multifocal, noncontiguous tumors;
      infiltrative local growth; vascular invasion; and malignant transformation. These
      pathological features seemed to support the hypothesis that the IMT is a
      neoplastic process, which has been augmented by reports that these tumors have
      clonal characteristics. Other studies have suggested that IMTs of the liver and
      spleen are associated with the Epstein-Barr virus. From the diagnostic
      perspective, there are several potential difficulties that the pathologist may
      encounter in the examination of one of these tumors. Just as it was true 60 years
      ago, the potential for a pathological diagnosis of one or another type of spindle
      cell sarcoma has not diminished with time. Because these tumors have a
      predilection for children, embryonal rhabdomyosarcoma is another diagnostic
      temptation when an IMT presents in the bladder or other hollow viscus. The IMT
      should probably be regarded as a soft tissue-mesenchymal tumor with an
      indeterminant or low malignant potential, which is a somewhat indefinite but
      realistic prognostic category.

PMID- 9606802
TI  - Inflammatory myofibroblastic tumor, inflammatory fibrosarcoma, and related
      lesions: an historical review with differential diagnostic considerations.
AB  - The concept of the inflammatory myofibroblastic tumor (IMT) has evolved from an
      already perplexing pathological process, the inflammatory pseudotumor, which was
      initially recognized in the lung and regarded as a pseudoneoplasm, although its
      histological features resembled a spindle cell sarcoma. Despite the pathological
      findings and their apparent prognostic implications, most affected individuals
      regardless of the primary site have had favorable clinical outcomes. The
      designation of inflammatory pseudotumor came to be widely accepted, although
      these lesions were clearly tumors or masses that may or may not have been
      pseudoneoplasms. An aberrant or exaggerated response to tissue injury without an
      established cause has generally been favored as the pathogenesis of the
      inflammatory pseudotumor or IMT. Once the myofibroblast was identified and its
      function in tissue repair was established, this cell type was found in a variety
      of soft tissue lesions from nodular fasciitis to malignant fibrous histiocytoma.
      The myofibroblast was eventually recognized as the principal cell type in the
      inflammatory pseudotumor, which provided the opportunity to redesignate this
      tumor as IMT. Some of the clinical and pathological aspects of the IMT began to
      suggest the possibility that these lesions are more similar to neoplasms than a
      postinflammatory process. Another step in the evolution of the inflammatory
      pseudotumor and IMT occurred with the report of a mesenteric or retroperitoneal
      tumor with similar pathological features to the latter tumors but with more
      aggressive behavior to warrant an interpretation of malignancy as an inflammatory
      fibrosarcoma. The IMT and inflammatory fibrosarcoma appear to have many
      overlapping clinical and pathological features. These tumors are histogenetically
      related, and if they are separate entities, they are differentiated more by
      degrees than absolutes. The therapeutic approach to these tumors should relay
      primarily on surgical resection. Studies in the future may possibly resolve the
      question whether the IMT and inflammatory fibrosarcoma are synonomous or closely
      related entities.

PMID- 9606803
TI  - Malignant neoplasms capable of simulating inflammatory (myofibroblastic)
      pseudotumors and tumefactive fibroinflammatory lesions: pseudopseudotumors.

PMID- 9606804
TI  - Inflammatory fibrosarcoma: update, reappraisal, and perspective on its place in
      the spectrum of inflammatory myofibroblastic tumors.
AB  - Inflammatory fibrosarcoma (commonly referred to as inflammatory myofibroblastic
      tumor) has become increasingly recognized as part of a spectrum of inflammatory
      myofibroblastic proliferations. It is a potentially locally aggressive
      myofibroblastic tumor that occurs predominantly in the mesentery of children and
      young adults. No reliable morphological parameters have been identified that
      predict prognosis. We evaluated the ultrastructural and immunophenotypic features
      of 16 cases of inflammatory fibrosarcoma and studied Ki67 (MIB1), PCNA, bcl-2,
      and p53 in an effort to identify prognostic markers. p53 was not detected
      immunohistochemically in any case. None of the markers were found to correlate
      with local recurrences, metastases, or tumor deaths. Low proliferative activity
      (Ki67 < 10%) was seen in all cases. A characteristic immunophenotype was
      reconfirmed in which lesional myofibroblasts stained for vimentin, alpha-smooth
      muscle actin, cytokeratins, and rarely desmin. Ultrastructural studies of seven
      cases confirmed the presence of a fibroblastic-myofibroblastic spectrum. Because
      inflammatory myofibroblastic tumor-inflammatory fibrosarcoma is associated with
      systemic symptoms, polymerase chain reaction studies for Epstein-Barr virus (EBV)
      and cytomegalovirus (CMV) were performed in 12 cases. Evaluable results in nine
      cases did not show evidence of either virus. The results of this study indicate
      that inflammatory fibrosarcoma has a low proliferative activity, which is in
      keeping with the impression that this is a low-grade sarcoma; that myofibroblasts
      can participate in true neoplasia; and that EBV and CMV do not play a role in the
      pathogenesis of inflammatory fibrosarcoma. The variable phenotype of the
      myofibroblast and its role in reactive and neoplastic processes are discussed. A
      perspective on the position of inflammatory fibrosarcoma in the spectrum of
      inflammatory myofibroblastic tumors is also given in light of the current study
      and the literature.

PMID- 9606805
TI  - Follicular dendritic cell tumor: review of the entity.
AB  - Malignant neoplasms showing follicular dendritic cell differentiation are
      uncommon. Most reported cases have involved lymph nodes of the neck, mediastinum,
      and axilla. Approximately 30% of the cases were located in extranodal sites, such
      as liver, tonsil, and intra-abdominal soft tissue. Microscopically, follicular
      dendritic cell tumor is composed of oval to spindle cells with eosinophilic
      cytoplasm arranged in sheets, fascicles, and whorls, sometimes admixed with foci
      showing a storiform pattern of growth. The tumor cells are characteristically
      admixed with small lymphocytes. The tumor nuclei are oval to spindle, with thin
      nuclear membranes, small basophilic nucleoli, and clear or dispersed chromatin.
      Scattered multinucleated tumor cells are frequently seen. Necrosis, marked
      cellular atypia, high mitotic rate, and abnormal mitoses may occur and are
      harbingers of an aggressive behavior. The tumor cells typically express CD21,
      CD35, Ki-M4p, Ki-FDRC1p, and vimentin, with occasional positivity for S-100
      protein, muscle-specific actin, and epithelial membrane antigen. Ultrastructural
      examination shows complex interdigitating cytoplasmic processes joined by
      desmosomes. The behavior of these tumors is more akin to that of a low-grade soft
      tissue sarcoma than a malignant lymphoma and is characterized by local
      recurrences in 36% of cases and metastases in 28%. A small proportion of cases
      have arisen against a background of Castleman disease of the hyaline-vascular
      type and others in association with Epstein-Barr virus infection. Complete
      surgical resection is the treatment of choice whenever feasible. Adjuvant
      radiotherapy or chemotherapy appears indicated in cases having adverse
      pathological features and in recurrent or incompletely resected lesions. Much
      still needs to be learned about the most effective adjuvant therapy and the
      molecular biology of these tumors.

PMID- 9606806
TI  - Detection of Epstein-Barr Virus in inflammatory pseudotumor.
AB  - Inflammatory pseudotumors appear to represent a heterogeneous group of diseases
      that share common histopathologic features. A subset of these tumors,
      particularly those in the spleen and liver, harbor the Epstein-Barr virus (EBV)
      in spindled cells. Methods for detecting EBV in these tumors and the reliability
      of the different detection methods are discussed. Some EBV-positive inflammatory
      pseudotumors contain an increase in EBV-positive follicular dendritic cells and
      demonstrate monoclonal EBV genomes. At least one such case has recurred locally
      as an unusual EBV-positive follicular dendritic cell tumor. These rare reports
      support the concept of a distinct EBV-positive, follicular dendritic cell type of
      inflammatory pseudotumor that may be at increased risk for local recurrence. Many
      more cases of this rare type of inflammatory pseudotumor must be studied and
      reported before the clinical validity of such a distinction can be proven.
      Although EBV detection in spindled cells is unusual, it has been demonstrated in
      rare smooth muscle tumors arising in immunosuppressed children and young adults.

PMID- 9606807
TI  - Idiopathic fibrosclerotic disorders and other inflammatory pseudotumors.
AB  - Fibroinflammatory disorders constitute heterogeneous clinical conditions whose
      cause and pathogenesis are largely unknown. Inflammatory pseudotumor has been
      applied in a generic sense to several of these disorders, which present as a mass
      displacing surrounding anatomic structures or leading to organ dysfunction
      secondary to compressive growth around the ureter(s), common bile duct, or great
      vessels in the mediastinum. The fibrosclerosing disorders of retroperitoneal
      fibrosis, sclerosing mediastinitis, sclerosing cholangitis, orbital pseudotumor,
      and Riedel thyroiditis are seemingly related in a clinical sense because there
      are well-documented cases of patients with two or more of these conditions and
      reports of these disorders presenting in family members. Although the
      pathogenesis of the fibrosclerotic disorders has not been elucidated,
      autoimmunity in the context of an established collagen vascular disease or the
      setting of inflammatory periaortitis in retroperitoneal fibrosis has been one
      suggested mechanism. In the course of the diagnostic evaluation of an individual
      with a suspected fibrosclerotic disorder, it is imperative to exclude an
      underlying infection or malignancy. This caveat is especially relevant to
      sclerosing mediastinitis as a presentation of histoplasmosis or to
      retroperitoneal fibrosis secondary to a sclerosing large cell lymphoma.
      Sclerosing mesenteritis has some clinical and pathological overlap with the
      fibrosclerotic disorders, but its nosologic and pathogenetic relationship is
      uncertain at this time. There are several other fibroinflammatory processes, such
      as focal myositis, inflammatory fibroid polyp of the gastrointestinal tract,
      calcifying fibrous pseudotumor, and sclerosing peritonitis, which are probably
      unrelated to inflammatory myofibroblastic tumor or the primary fibrosclerotic
      disorders.

PMID- 9606808
TI  - Dysregulation of apoptosis as a mechanism of liver disease: an overview.
AB  - Apoptosis is a morphologically distinct form of cell death which occurs in a wide
      variety of liver diseases. In this overview chapter, we review: (1) the current
      definitions of apoptosis; (2) the biochemical pathways effecting apoptosis; and
      (3) the intracellular pathways regulating apoptosis. We also describe how
      apoptosis is identified in the liver and review the ligand/receptor interactions
      which trigger hepatobiliary apoptosis. Finally, we speculate on potential
      therapeutic applications for modulating apoptosis in human liver diseases. This
      information is meant to provide a foundation for the following chapters each
      focused on a specific role of apoptosis in liver diseases.

PMID- 9606809
TI  - Dysregulation of apoptosis in hepatocellular carcinoma.
AB  - The tightly controlled homeostatic mechanisms between cell growth and apoptosis
      that exist in normal liver tissue are disrupted during hepatocarcinogenesis. The
      TGF (transforming growth factor)-beta signaling system is a central component of
      the mechanisms by which cell growth and apoptosis are controlled in the liver.
      The recent delineation of the TGF-beta signaling pathway has provided a unique
      framework for analysis of the impact that disruption of individual components of
      this signaling pathway can have on apoptosis during hepatocarcinogenesis. Here we
      review recent data on involvement of the TGF-beta signaling pathway in the
      dysregulation of apoptosis frequently observed in hepatocellular carcinomas. The
      data indicate that disruption of the TGF-beta pathway at the pre-receptor,
      receptor, and post-receptor levels occurs in hepatocellular carcinomas and can
      cause dysregulation of apoptosis. Also, substantial evidence now exists that
      phosphatidylinositol-3-kinase (PI3K) may function as an important negative
      regulator of the TGF-beta 1-induced apoptosis in hepatocellular carcinomas. Taken
      together, the available evidence indicates that disruption of the TGF-beta 1
      induced apoptosis as well as growth inhibition is an important and integral part
      of the multistage process of liver carcinogenesis.

PMID- 9606810
TI  - Regulation of apoptosis-associated genes in the regenerating liver.
AB  - The ability of the liver to regenerate remains a fascinating response to hepatic
      injury. Ever since the Greek myth of Prometheus, efforts have been made to
      unravel the mechanisms involved in liver regeneration. The cellular phenomenon
      represents an orchestrated response to external stimuli followed by sequential
      changes in gene expression, cytokine production, and morphologic structure. The
      most popular experimental model is based on the surgical removal of two-thirds of
      the liver. The remnant lobes respond to the loss of mass and function with
      expression of immediate- and delay-early genes which prime the cells for eventual
      progression through the cell cycle. The molecular events which trigger liver
      regeneration are now beginning to unfold. However, the control of liver
      regeneration and the events involved in regulating the three-dimensional growth
      of the organ remain poorly defined. It now appears that apoptosis probably plays
      a key role in fine tuning the regenerative response. The list of apoptosis
      related gene products seems to grow regularly and includes both pro- and
      antiapoptotic factors. It is noteworthy that many of these genes are critical
      mediators of both apoptosis and cell replication. The factors involved in
      predicting which pathway they chose provide the basis for uncovering the secrets
      of organ growth--be it by life or by death.

PMID- 9606811
TI  - CD95-induced apoptosis in human liver disease.
AB  - The CD95 receptor is a death receptor capable of transducing apoptotic cell death
      upon ligation with the CD95 ligand (CD95L). The CD95/CD95L system plays a
      physiological role in apoptosis of lymphocytes and liver cells. In addition, the
      striking finding of acute hepatic failure in mice upon CD95 triggering has
      stimulated general interest in the involvement of CD95 mediated apoptosis in
      human liver disease. The currently available data point to a deregulated CD95
      system in viral hepatitis, alcoholic hepatitis, acute hepatic failure of
      different etiology, diseases of the bile ducts, and hepatocellular carcinoma.
      Animal experiments suggest a causative relationship between CD95 activation and
      liver cell death, which, however, still has to be proven for liver disease in
      man. This review summarizes our present knowledge on CD95 mediated human liver
      disease.

PMID- 9606812
TI  - Apoptosis as a mechanism of tissue injury in liver allograft rejection.
AB  - Recent studies suggest that apoptosis is an important mechanism of cell death in
      the rejection of liver allografts and that infiltrating host lymphocytes mediate
      this process. The first section of this chapter addresses the cells and molecules
      that initiate the immune response following transplantation of a liver allograft.
      The recognition of donor alloantigens by infiltrating host lymphocytes stimulates
      a cascade of immune events which culminate in development of the effector cells
      that mediate tissue damage. Studies which demonstrate that apoptosis of
      hepatocytes and bile duct cells accompany allograft rejection are detailed in the
      second section of this chapter. The final section discusses the potential
      pathways which lead to apoptosis in liver allograft rejection. The contributions
      of the granule-exocytosis pathway, the Fas-mediated pathway, and cytokines to the
      induction of apoptosis in liver allografts are discussed. In addition, the
      concept that alloreactive graft infiltrating cells are deleted by apoptosis is
      presented. A further understanding of the mechanisms involved in apoptosis will
      lead to unique approaches toward the goal of achieving allograft tolerance.

PMID- 9606813
TI  - Apoptosis and viral hepatitis.
AB  - Viral hepatitis is a diffuse inflammatory reaction of the liver caused by
      hepatotropic viruses. Pathomorphologic studies have shown acidophilic bodies and
      hepatocyte dropout, features that are compatible with apoptosis. Using in situ
      terminal transferase labeling, the number of hepatocytes showing features of
      apoptosis in patients with chronic hepatitis B and C was found to be small but
      higher than healthy subjects, indicating that apoptosis is involved in the
      pathogenesis of these diseases. There is evidence that the immune (cytotoxic T
      lymphocyte)-mediated pathways of apoptosis are activated, suggesting that the
      apoptosis of liver cells may at least in part be related to the host immune
      defense. Whether other cytokine-mediated and cellular constitutive apoptotic
      pathways are involved or not remains to be studied. There are recent data
      suggesting that hepatitis B and C viral proteins may modulate apoptosis. The
      exact role of these observations in relation to pathogenesis remains to be
      established.

PMID- 9606814
TI  - Dysregulation of apoptosis in the cholangiopathies and cholangiocarcinoma.
AB  - The importance of cholangiocytes, the epithelial cells lining bile ducts, in the
      biology and pathobiology of biliary epithelia is rapidly growing due to the
      advent of suitable experimental models and techniques to study these cells.
      However, the role of cholangiocytes as a major cellular target in a variety of
      severe hepatobiliary diseases or cholangiopathies remains unanswered. As the
      biology of cholangiocyte death evolves, apoptosis has emerged as a key player in
      the development of ductopenia in these cholangiopathies. Cholangiocytes are
      continuously exposed to a variety of genotoxic insults, such as chronic
      inflammation and hydrophobic bile acids. This chronic exposure may predispose
      cholangiocytes to oncogenic mutations and the further progression to malignancy
      (or cholangiocarcinoma [CC]), due, in part, to failure to activate apoptosis and
      delete cells with genetic damage.

PMID- 9606815
TI  - Apoptosis and alcoholic liver disease.
AB  - Apoptosis occurs in both clinical and experimental alcoholic liver disease. The
      mechanisms involved in alcohol-induced apoptosis of liver cells are not
      completely understood. Induction of cytochrome P450 2E1, the alcohol-inducible
      cytochrome P450, is one of the proposed mechanisms. Exposure of Hep G2 cells
      expressing cytochrome P450 2E1 to arachidonic acid leads to increased lipid
      peroxidation and apoptosis. Increased levels of iron in the liver also promote
      lipid peroxidation and are associated with increased numbers of apoptotic
      hepatocytes. Tumor necrosis factor (TNF) acting through its receptors can induce
      apoptosis in hepatocytes. Increased levels of tumor necrosis factor and its
      receptors have been described in alcoholic liver disease. The liver is also CD95
      receptor positive and in liver tissue from patients with alcoholic hepatitis, the
      CD95 ligand is expressed at high levels in hepatocytes. Cytotoxic T lymphocytes
      could, through the CD95 receptor-ligand interaction, promote apoptosis.

PMID- 9606816
TI  - Preadmission psychosocial screening of older orthopedic surgery patients:
      evaluation of a Social Work Service.
AB  - A preadmission social work intervention was evaluated for impact on length of
      hospital stay (LOS) and patient satisfaction. Psychosocial issues related to
      function and post-discharge needs were assessed at an exploratory level. A
      modified post-test only control group design was used. Study group patients were
      screened before hospitalization and offered services on admission. Control group
      patients received standard care. Study group patients were significantly more
      satisfied with services but impact on length of stay was not demonstrated with
      one possible exception. Post-operative complications were significantly related
      to longer LOS; however, unlike control group patients, study group patients with
      complications did not have significantly longer LOS. Women and those limited in
      preadmission physical function were most likely to report insufficient help after
      discharge. A more intensive preadmission intervention is recommended to improve
      impact on LOS and informal support system involvement, while future outcome
      studies would clarify the nature of service gaps and high risk groups.

PMID- 9606817
TI  - Interdisciplinary health care and female victims of domestic violence.
AB  - Female victims of domestic violence often face uncertainty in hospital emergency
      rooms. Victims may encounter physicians, nurses, social workers, and other health
      care providers who do not work collaboratively, have limited knowledge of
      domestic violence, and express negative attitudes. Hence, treatment outcomes may
      be negative. A retrospective case study of 153 medical records of female victims
      at two Midwestern hospital emergency medicine departments was completed. Findings
      suggest positive treatment outcome where interdisciplinary collaboration was
      evident. Included were more accurate assessments in terms of past history, more
      descriptive emotional symptoms displayed by victims, and written documentation of
      recommendations concerning intervention and linkage to community resources.
      Implications for policy and interdisciplinary training are discussed.

PMID- 9606818
TI  - Consequences of adolescent pregnancy/parenting: a review of the literature.
AB  - This article reviews the empirical literature on the consequences of adolescent
      parenting in the arenas of economic impact, health risks to mother and child,
      parenting practices, and cognitive and behavioral performance of children. These
      consequences are divided between the direct effects of adolescent pregnancy and
      indirect effects, the latter of which are the socioeconomic and background
      correlates that also contribute to the risk of adolescent pregnancy, such as
      socioeconomic status, educational level, family structure, and family size. From
      this review of factors, social work practice and policy recommendations to reduce
      risk will be explored.

PMID- 9606819
TI  - A risk profile of emergency room adult trauma victims: intentional versus
      unintentional trauma injuries.
AB  - This article presents a prospective study of 285 adult trauma victims admitted to
      a Los Angeles inner-city level 1 trauma center, from November 1991 to February
      1992. The purpose of this study was to determine the magnitude of intentional and
      unintentional trauma injuries in this adult patient population, and to identify
      sociodemographic, lifestyle and medical risk factors predisposing patients to
      intentional vs. unintentional trauma injury. Chi-square analysis revealed that
      intentional trauma victims and unintentional trauma victims significantly differ
      in 8 of 13 risk factors. The resulting risk profile indicated that intentional
      trauma victims were more likely to be between the ages of 16-29 years old;
      African American males and more likely to present to the emergency room with
      injury severity scores higher than 15 (indicating severe injuries) than
      unintentional trauma victims. Strategies for prevention and medical social work
      intervention are discussed.

PMID- 9606820
TI  - [Vitamins E and C as components of the antioxidant system in avian and mammalian
      embryos].
AB  - New information about functional properties and peculiarities of alpha-tocopherol
      and ascorbic acid interaction in birds embryos organism with providing of
      adequate antioxidant status in embryogenesis and early ontogeny are given. Some
      characteristics of these natural antioxidants action in different embryonal
      tissues on the inhibition of lipids peroxidation processes depending on their
      level in the organism are shown.

PMID- 9606821
TI  - [Structural organization of Na+,K+-ATPase isoenzymes in the plasma membrane].
AB  - A current state of the researches related to structural arrangement of the
      Na+,K(+)-ATPase in the plasma membrane determining high lipid dependence of the
      enzyme has been reviewed. The membrane properties of the Na+,K(+)-ATPase
      isozymes, which specific features have been ascertained when investigating their
      thermal stabilities, sensitivities to phospholipases, detergents, etc., are
      considered more in detail. The existence of differences in structural
      organization of boundary lipids of the neuronal Na+,K(+)-ATPase catalytic subunit
      isoforms is supposed. The adaptive significance of the revealed specificity of
      the neuronal lipid microenvironment of the Na+,K(+)-ATPase isoforms is assumed.

PMID- 9606822
TI  - [Three-dimensional model of the fibrin(ogen) molecule and fibrin fibril].
AB  - The paper deals with the three-dimensional model of fibrin(ogen) molecule and
      fibrin fibril, based on the electron microscopy data on fibrin(ogen) molecule and
      on fibrin fibril structure, data on symmetry of fibrinogen primary structure, on
      domain structure of molecule, on location of sites of polymerization and on the
      data on polymerization mechanism of fibrin.

PMID- 9606823
TI  - [Methods for studying the fibrinolysis system and its components].
AB  - Comparative analysis of the methods of estimation of the state of fibrinolytic
      system and its components, which are used in clinical practice now is presented
      in the review. The advantages of the approaches, which are based on the
      simultaneous determination of several indices of this system were considered. It
      was shown promising to use these methods in ophthalmology for estimation of both
      common and local (in liquids and eye tissues) haemostats, as important additional
      diagnostic and prognostic criteria of development of some ophthalmopathologies.

PMID- 9606824
TI  - [Cytosolic thiamine triphosphatase from bovine brain. 1. Regulation of enzyme
      activity].
AB  - The steady-state kinetics of the ThTP hydrolysis by thiamine triphosphatase (EC
      3.6.1.28) from bovine brain testified to the presence of two kinetically
      significant conformational states of the protein, their equilibrium being
      determined by the substrate concentration. The ThTPase isomeric forms had
      different activities, affinities for ThTP and activation energies. The form with
      high affinity for the substrate was characterized by the Km and Vmax values of 43
      microM and 9.9 mumol.s-1.mg-1 whereas for the form with lower affinity these
      values were equal to 298 microM and 19.3 mumol.s-1.mg-1, respectively. The
      activation energies of the ThTP hydrolysis reactions were 85.3 and 47.1 kJ.mol-1.
      Several mechanisms of the enzyme activity regulation in the cell are suggested.
      One of the mechanisms is related to the allosteric ThTP effect inducing
      reversible transition of the protein to a more active conformational state, while
      the others include the inhibition activity by ATP and the activation of ThTP-ase
      by Mg2+ free ions.

PMID- 9606825
TI  - [Effect of x-irradiation on properties of Ca2+-calmodulin-dependent protein
      kinase from rat spleen lymphocytes].
AB  - Ca(2+)-calmodulin-dependent kinase has been isolated and purified from rat spleen
      lymphocytes cytosol in control and 12 h after the effect of X-ray radiation in a
      dose of 0.5 and 1 Gy. The isolated enzyme showed a remarkable similar substrate
      specificity and kinetic properties to those of rat brain and rat spleen
      calmodulin-dependent protein kinase II.

PMID- 9606826
TI  - [Effect of temperature acclimation on glucose-6-phosphate dehydrogenase activity
      in various tissues of the Mullus barbatus ponticus].
AB  - Acclimation of the Mullus barbatus ponticus to the temperature fall (from 16 to 8
      degrees C) induces an increase in the activity of glucose-6-phosphate
      dehydrogenase both in summer and in autumn. These changes are more expressed in
      the liver and red muscle than in the white ones. The values of Km of glucose-6
      phosphate (only in autumn) and NADP are also higher at 8 than at 16 degrees C.
      Actinomycin D does not prevent from cold activation of this enzyme in liver only
      in autumn, when the activity of glucose-6-phosphate dehydrogenase is 8-10 times
      higher than in summer, and in the red muscle in the both seasons, although this
      injection decreases the level of enzyme activity in this muscle. This injection
      does not change the values of Km for glucose-6-phosphate and NADP. It is supposed
      that the activation of glucose-6-phosphate dehydrogenase in the liver and red
      muscle during cold adaptation may be a result of change of substrate-binding
      ability and enzyme interaction with NADP without changes in the enzyme
      biosynthesis.

PMID- 9606827
TI  - [Effect of N-palmitoylethanolamine on energy-dependent transport of Ca2+ in
      vesicles of myometrium sarcolemma and their phospholipid composition].
AB  - N-palmitoylethanolamine (NPE) was studied for their effect on calcium pump of pig
      myometrium sarcolemma. NPE in concentration of 10 microM, stimulated by 28-46%
      Mg2+, ATP-dependent accumulation of Ca2+ in vesicles of plasmatic membrane of
      uterus myocytes taking absolutely no effect on passive release of this cation
      from them. NPE modified phospholipid composition of sarcolemma, causing the
      increase of percentage content of phosphatidylinositol (by 20.2%) and
      lysophosphatidylcholine (2.7 times). While NPE effects transport Ca2+, Mg(2+)
      ATPase solubilized from plasmatic membrane and purified due to the method of
      affinity chromatography on calmodulin-sepharose 4B, no activating effect of NPE
      on the calcium pump was observed. And what is more, a weakly expressed tendency
      to inhibition (by 14-15%, respectively) of the rate of Ca2+, Mg(2+)-dependent
      enzymic hydrolysis of ATP has been revealed. It is supposed that the effect of
      NPE on active transmembrane transport of Ca2+ is an important link in the general
      mechanism of contraction-relax of the myometrium and is, apparently, connected
      with its modifying effect on the lipid composition of the sarcolemma.

PMID- 9606828
TI  - [Effect of n-palmitoylethanolamine on energy-dependent transport of Ca2+ in
      intracellular structures of myometrium and their phospholipid composition].
AB  - N-palmitoylethanolamine (NPE) was studied for its effect on the systems of energy
      dependent transport of Ca2+ in the intracell structures (mitochondria,
      endoplasmic reticulum) of permeabilized cells of smooth muscles of the rat uterus
      as well as on the lipid composition of myocytes. NPE in concentration of 10(-5) M
      partially (by 30-50%) inhibited energy-dependent accumulation of Ca2+ in
      endoplasmic reticulum and mitochondria of myometrium cells permeabilized by means
      of treatment of myocytes suspension by digitonin (0.1 mg/ml). NPE modifies the
      lipid composition of permeabilized myocytes when determining the increase of the
      amount of inorganic phosphorus of total phospholipids by 57.3% at the expense of
      considerable accumulation of phosphatidylcholine, phosphatidylethanolamine and
      sphingomyelin. It is supposed that the effect of NPE on the systems of energy
      dependent transport of Ca2+ is achieved through the modification of phospholipid
      composition of a cell, while modulating effect of NPE on the active transmembrane
      transfer of Ca2+ in the intracellular structure can be an important link in the
      general mechanism of the effect of this compound on Ca2+ metabolism in myometrium
      and on Ca(2+)-depended control of the contracting function of the uterus.

PMID- 9606829
TI  - [Effect of H+ extracellular and intracellular buffering capacity on the activity
      Ca2+/H+ exchange in the lymphocyte plasma membrane].
AB  - Formation of delta pH is registered when studying Ca2+ passive transport through
      lymphocytes' plasma membrane (PM). The pHi values strongly depended on pH0.
      Changes of pH0 lead to unidirectional changes of pHi and affect Ca2+
      concentration in cytoplasm of the intact cells. The presence of Ca(2+)-channels
      antagonists does not affect this phenomenon. Ca2+/H+ exchange is supposed to
      exist in PM. It is also of great interest that cytoplasmic Ca2+ and H+ activities
      are some equal in physiological range. Besides, H(+)-buffering as well as Ca(2+)
      buffering systems are present in the cell and have their maximal capacity about
      7.2 in the intact cells. The spectrofluorimetric study of internal lymphocytes'
      H(+)-buffering capacity with titration technique using weak base, acid or other
      buffer addition has demonstrated maximal value of 9.0-1.1 mM depending on the
      substance to be added.

PMID- 9606830
TI  - [Structural changes in membranes of proliferating leukocytes L-41 as affected by
      low doses of ionizing radiation].
AB  - The dose-dependent effects of gamma-radiation on the leucocyte cultures L-41 has
      been investigated. Irradiation by the dose of 0.25 Gy stimulates the cell
      proliferation while that by the doses of 1.0 and 2.0 Gy inhibits this process. In
      this dose range the radiohormesis effects characterizing structural organization
      of the probed membranes have been also registered for fluorescence parameters.
      The zone of qualitative transition of response of the cell membranes to radiation
      is individual for various effects. The action of radiation in the doses of 0.25
      and 0.50 Gy induces a decrease of ANS fluorescence intensity and a decrease of
      membrane protein immersion in the lipid bilayer of leukocyte membranes. The
      values of these parameters rise at the doses of 1.0 and 2.0 Gy that reflects
      different directions of structural changes in various membrane regions. The
      irradiation in the range of 0.25-1.0 Gy induces the increase of microviscosity in
      deep regions of membrane lipid matrix while at the dose 2.0 Gy it causes its
      decrease. Radioactive radiation does not change the membrane protein conformation
      of leukocytes and polarity of lipid bilayer hydrophobic zones as recorded by
      fluorescent methods used.

PMID- 9606831
TI  - [Transformation of serum immunoglobulins and monoclonal antibodies into
      polyreactive immunoglobulins].
AB  - It was shown that polyreactive properties of natural serum immunoglobulins or
      some monoclonal antibodies (i.e. their ability of binding to various
      antigenically dissimilar antigens) can be induced by the treatment with
      chaotropic ions (3.5 M KSCN, 5-30 min at 20 (C). Such transformation of
      monoclonal antibodies or serum immunoglobulins into polyreactive immunoglobulins
      (PRIG) seems to result of the changes in immunoglobulin conformation but is not
      from their unblocking. Interaction of PRIG with some antigens immobilized on the
      plate is strongly dependent on temperature unlike that of monospecific
      antibodies.

PMID- 9606832
TI  - [Heparin effect on hydrolysis of fibrin clots in a bull and a man with varying
      fibrinolytic systems].
AB  - Heparin was studied for its effect on the hydrolysis time of clots from desAA
      fibrin (FB), desAABB fibrin (F0) and fibrinogen (Fg) of a bull and a man by gly
      or lys-plasminogen which is activated by the tissue activator. It is shown that
      heparin in the concentration to 4.6 M does not affect that hydrolysis time of
      clots from human and bovine Fg and human Fg by gly-plasminogen which is activated
      by the tissue activator. Heparin increases the hydrolysis time of clots from
      bovine Fg and F0 by gly-and lys-plasminogen, the tissue activator being present.
      It firstly increases (in concentrations below 0.5 (microM), and then decreases
      (in concentrations above 0.5 (microM) the hydrolysis time of clots from human FB,
      F0 and Fg and bovine FB and F0 by plasmin. In concentration 4.6 microM heparin
      increases the hydrolysis time of clots from human fibrinogen by fibrinolytic
      systems. Effect of heparin on fibrinolytic process from the viewpoint of affine
      interactions between the components of fibrin clots is discussed.

PMID- 9606833
TI  - [The identification of internal symmetry in primary structure of cytoplasmic
      domains of human insulin receptor beta-subunit].
AB  - The graphic method of analysis for identification of internal symmetry centres in
      amino acid sequences (AAS) of insulin receptor (IR) cytoplasmic 'tail' was used.
      The method was based on the comparison of normal and conversional sequences (AAS
      or sequences of amino acid codon roots). It was shown, that the regions of IR
      cytoplasmic domains most important for receptor functional activity possess
      symmetrical structure. The regions participate in the autophosphorylation,
      tyrosine kinase activity, ATP-binding, interaction with different types of G
      proteins, processing of receptor molecule, etc. The functionally important amino
      acids and their clusters either were included in the formation of the internal
      symmetry centres or were localized close to them.

PMID- 9606834
TI  - [Role of proton-motive force in the conjugative DNA transport in Staphylococci].
AB  - Sensitivity of the conjugative process in staphylococci to the action of
      uncouplers of oxidative phosphorylation and inhibitors of electron transport
      systems have been proved, that testifies to the energy-dependent character of
      conjugative transport of DNA. Proceeding of the conjugation process depends upon
      the generation of delta microH+ on the membrane of both the donor and recipient
      cells. contribution of protonmotive forces to providing for the transfer of
      plasmids during conjugation to staphylococci has been defined.

PMID- 9606835
TI  - [Physico-chemical properties of there phages of Pseudomonas syringae].
AB  - The properties of DNA for 9B, 123, 788/8 phages lysing phytopathogenic
      Pseudomonas syringae bacteria have been analysed with results presented. It was
      ascertained that their genomes consist of GC-type two-chain DNA molecules having
      molecular weight 14-15 mDa. It was shown that sedimentation coefficient for all
      three phage DNA is identical and equals 26S. GC-base percentage was calculated
      for the phage genomes. Its value, according to results of sedimentation analysis
      and melting temperature, was the same for 9B (51%, 57%) and 123 (51%, 57%) and
      differed for 788/8 (53%, 60%). The molecular weight of DNA phages calculated from
      the sum of fragments, obtained after genome splitting with restriction
      endonucleases is in agreement with the data of sedimentation analysis. The
      distribution of phage DNA fragments if electrophoregrams suggests the presence of
      numerous common restriction sites in the phages' genomes.

PMID- 9606836
TI  - [Content and composition of lipoproteins of rat blood and liver and various
      parameters of oxidative stress during administration of cobalt chloride].
AB  - Cobalt chloride effect on rat liver and serum blood lipoproteins content and
      composition and on some characteristics of lipid peroxidation and oxidative
      stress was investigated. The activation of free-radical oxidation and oxidative
      stress development were judged from the dynamics of lipid peroxidation products
      accumulation, from cathepsin D unsedimental activity and from the alteration of
      microsomal cytochrome P-450 content and from activity of a number antioxidative
      enzymes. In order to evaluate the state of glutathione-defence system the
      activities of glutathione peroxidase, glutathione S-transferase, glutathione
      reductase and some NADPH-generating enzymes and reduced glutathione level
      alteration were studied in liver. The data obtained show that the cobalt chloride
      injection leads to the development of the oxidative stress and to activation of
      some antioxidant defence system, namely, glutathione-depending enzymes, and of
      microsomal cytochrome P-450 catabolism. The system blood lipoproteins (liver
      lipoproteins was found to participate in metabolism adaptation under oxidative
      stress and in maintenance of biological membranes structure and functioning.

PMID- 9606837
TI  - [Selenium as a modifier of antioxidant protection and lipid peroxidation in
      microclones of Arnica montana L. as affected by C-range ultraviolet rays].
AB  - selenium was studied for its effect on the node components of antioxidant
      protection of plants irradiated by UV of C-range. It is shown that selenium
      modifies the UV action of C-range and decreases the oxidation of SH-groups,
      increases activity of superoxide dismutase and glutathione peroxidase and
      decreases the accumulation of the end product of peroxidation: malondialdehyde.

PMID- 9606838
TI  - [Protein synthesis in maize haploids and diploids during cultivation under normal
      conditions and in the presence of phenol].
AB  - 14C-leucine incorporation in cytoplasmic protein was compared for three haploid
      forms, three derivative autodiploid lines and four hybrid forms of maize. It has
      been found that the precursor incorporation in the haploid forms was by 15-20%
      higher that in appropriate autodiploid lines. However, the level of protein
      synthesis wes practically the same for all investigated diploid forms. Thus, the
      increase of the ploidy level correlates with the decrease of the cytoplasmic
      protein synthesis. It was also shown that the protein content was practically
      equal in haploid and diploid forms. Proceeding from the authors' data one can
      conclude that the protein distraction may also have different intensity. The next
      step of the investigation was the study of the effects of the chemical factor of
      cytoplasmic protein synthesis in maize seedlings with different ploidy levels in
      vivo. It has been revealed, that the rate of 14C-leucine incorporation in the
      cytoplasmic proteins differ for the haploid forms which grew on the Knop media
      with the addition of phenol (0.05%) and without pollutant. Nevertheless,
      approximately equal level of 14C-leucine incorporation was observed for
      autodiploids. Recently it was demonstrated that the synthetic intensity of
      different RNA fractions is higher in the haploid maize forms than in the diploid
      ones and that the haploid and diploid forms of maize display the different
      reaction on phenol pollution. When comparing our data with the published results
      it is possible to conclude that the hypothesis about the low intensity of
      metabolism in haploid plants, existing in literature, is not true. The authors
      suppose that the high activity of synthesis of nuclear, transfer and ribosomal
      RNA and cytoplasmic proteins in the haploid plants may be connected with high
      mitotic activity. The authors' data are in agreement with the hypothesis that the
      ratio of nuclear volume and surface determines the metabolism rate.

PMID- 9606839
TI  - [Biochemical characterization of noduleless soybean lectins].
AB  - The comparative analysis of activity and hydrocarbon specificity of lectins from
      common soybean and soybean in which roots the nodules do not form has been
      carried out. It was shown that the root lectins possesses the less activity in
      comparison with the seed lectins. The both kinds of lectins most specifically
      link with mannitol. The supposition was made about the role of activity and
      hydrocarbon specificity of lectins from soybean in the establishment of symbiotic
      systems of nitrogen fixation.

PMID- 9606840
TI  - [Content of arachidonic acid metabolites in blood and saliva of children with
      bronchial asthma].
AB  - The rise of the thromboxane B2, leukotriene B4 and prostaglandin F2a
      concentration in the blood and saliva of children was revealed during the attack
      of the bronchial asthma. At the same time the content of the prostaglandin E2 and
      prostacyclin in these biological fluids was reduced. The level of the eicosanoids
      in the examined liquids was correlated with the severity of bronchial asthma
      proceeding and with the adrenal glands function, which activity was also reduced.

PMID- 9606841
TI  - [Change in prostanoid metabolism in cystic kidney lesion].
AB  - A wide range of renal prostaglandins in cysts has been studied as compared with
      their content in the daily urine, activity of plasma renin, level of
      adrenocorticotropic hormone (ACTH) in the tissues, methionine enkephalin and
      aldosterone. High activity of renin, met-enkephalin and ACTH was observed in the
      patients with one cyst. Under renal polycystosis the activity of plasma renin is
      higher and the amount of ACTH positively decreases. The comparison of prostanoids
      content in the cystic fluid of a single cyst and polycystic one demonstrates that
      the polycystic level of all prostanoids in the punctate increase 2-3 times.

PMID- 9606843
TI  - [Hemostasis in patients operated on for abdominal hemorrhage. 3. Boundary
      deviations of hemostasis].
AB  - The fibrinolytic process in the plasma of patients operated for abdominal
      haemorrhages have been investigated. The results allowed to conclude that the
      blockade of fibrinolysis did not effect on the course of the disease. The high
      level of the inhibitors and of the platelets hypoaggregation can be considered as
      a cause increased of the recurring gastrointestinal haemorrhages. It was
      demonstrated that the probability of DIC-syndrome development increased at the
      aggravation of the patient's state after the operation.

PMID- 9606842
TI  - [Hemostasis in patients operated on for abdominal hemorrhage. 2. Characterization
      of the process of activation of blood coagulation system factors. Coagulation
      inhibitors].
AB  - Haemostasis indexes were estimated in four groups of patients which were isolated
      by the cluster analysis and operated for abdominal haemorrhages. A tendency or
      explicit hyperfibrinogenemia have been fixed which are connected with the
      syndrome of the system inflammation response of the patient in the critical
      state. The correlation between the indexes of the prothrombin time, activated
      partial prothrombin time and protein C activity is shown. An analysis of
      anticoagulants effect suggests it possible to consider the antithrombin III to be
      the main, stable blood anticoagulant, while protein C is responsible for the
      operational response of the organism on the part of haemostasis. The decrease of
      ancystron and thrombin time was recorded in 50% of patients notwithstanding the
      hyperfibrinogenemia and presence of fibrin fibrinogen degradation products. It is
      supposed that the acceleration of fibrin polymerization in the examined groups of
      patients is the mechanism of the organism protection from the blood loss under
      the given pathology.

PMID- 9606844
TI  - [Hemostasis in patients operated on for abdominal hemorrhage. 4. Conception of
      hemostasis changes].
AB  - Studies of haemostasis changes in the dynamics of early post-operational period
      permitted revealing the tendency to the growth of fibrinogen concentration,
      decrease in the fibrinogen self-assembling rate, weakening of thrombinemia,
      disturbances in fibrinogen degradation products (FDP) elimination, increase of
      inhibitors activity and/or weakening of blood coagulation factors activity,
      intensification thrombocytes aggregation. Hypercoagulation has been registered
      under acute haemorrhage and the haemorrhage time exceeding 24 h before the
      operation, the weakening of hypercoagulation response was observed,
      notwithstanding the possibility of haemorrhage continuation. The letter is
      underlined by the changes in the balance between the coagulation factors and
      inhibitors up to the absence of typical hypercoagulation response to surgical
      interference.

PMID- 9606845
TI  - [Effect of caffeine on xanthine oxidase activity].
AB  - The effect of caffeine on the xanthine oxidase activity in human organism has
      been studied. It was revealed that caffeine calls the inconsiderable reliable
      increase of the level of uric acid and the reliable lowering of levels of
      hypoxanthine and xanthine in urine. The isosteric inhibition of xanthine oxidase
      activity by caffeine was revealed in the experiments in vitro. It was proved that
      caffeine cannot be the inhibitor of xantine oxidase in vivo because it
      demethylases to I-methylxanthine.

PMID- 9606846
TI  - [Characterization of amino acid composition of lectin from noduleless soybean].
AB  - The amino acid composition of lectin from noduleless soybean has been
      investigated. It is shown that contents of threonine, serine and proline are
      higher but contents of tyrosine, phenylalanine and histidine are lower as
      compared with those in lectin from common soybean. The conclusion is made about
      the significance of amino acid composition of soybean lectin for its symbiotic
      properties.

PMID- 9606847
TI  - [Use of the computer simulation method of complementary amino acids base on a
      genetic code algorithm for the search for new peptide compounds belonging to
      tuftsin-like activity].
AB  - Methods of k-neighbours and neural networks were used for prediction of
      pharmacological effects of new compounds wits tuftsin-like activities. The tested
      compounds were constructed by the complementarity rule of genetic code algorithm.
      Five of seven substitutions with stereocomplement amino acids in the tuftsin
      sequence lead to new active compounds. Thus, the use of amino acid complementary
      code can be a helpful tool for the construction of a new immunomodulating
      peptide.

PMID- 9606848
TI  - [Disturbance of equilibrium between blood levels of antioxidant and prooxidant
      metalloproteins in pain stress in children].
AB  - Molecular mechanisms of the trauma stress of different origins in children to
      some extent is related to the quantitative changes of blood superoxide dismutase,
      catalase, ceruloplasmin, transferrin, cytochromes b5, b558III, b558IV and suprol.
      Non adequate changes of antioxidant (superoxide dismutase, catalase,
      ceruloplasmin, transferrin) and newly discovered prooxidant (cytochromes b5,
      b558III, b558IV, suprol) metalloproteins, as well as serum and erythrocyte
      cytochrome b5 depend on characteristic and duration of trauma stress caused by
      extremity fractures in children. This is due to the different mechanisms of
      adaptation to trauma stress.

PMID- 9606849
TI  - "Proteinase trace" in slow transmissible diseases?

PMID- 9606850
TI  - [Results of cement-free implanted, Robert Mathys isoelastic acetabular cup].
AB  - In 163 patients--125 (76.7%) female, 38 (23.3%) male--172 cementfree isoelastic
      acetabular cups were implanted. The average patient age was 72.6 years (range: 16
      to 96 years). Sixty-seven (41.1%) patients with 72 (41.9%) cups could be followed
      up for an average of 6.0 years (range: 2.0 to 12.2 years) after the procedure.
      Using the Harris-hip-score we found 49 (68.1%) "very good" to "fair" results. In
      23 (31.9%) hips scoring had to be classified as "bad". The rate of cup-loosenings
      in the collective was low at 3.5% (6/172), probably due to the reduced physical
      activity of our comparatively older patients. Because after the 8th year
      symptomatic loosening must be routinely expected, the procedure is not indicated
      for younger patients. In older patients with femoral neck fractures the
      cementfree isoelastic acetabular cup has proven itself effective in our
      experience.

PMID- 9606851
TI  - Treatment of distal femoral fractures in the elderly. Results with the retrograde
      intramedullary supracondylar nail.
AB  - The drawbacks of plating techniques for the treatment of distal femoral fractures
      are the need for a large exposure with the possible risk of soft tissue damage,
      devascularisation of bone fragments and loss of the possible positive effect of
      the fracture hematoma. Moreover, early weight bearing is not advisable with these
      implants. To find out whether the retrograde nailing of distal femoral fractures
      is beneficial we performed this study. Between March 1, 1993 and September 1,
      1995, 25 patients with 26 distal femoral fractures were treated in our department
      with retrograde femoral nailing. According to the ASIF-classification we
      classified 20 fractures as supracondylar A fractures and 6 fractures as
      intercondylar C fractures. All fractures were closed and without important soft
      tissue damage. One patient dies of a not fracture-related cause before fracture
      healing was achieved. Twenty-five fractures healed. According to our relative
      Neer-score we counted 18/25 (72%) excellent results (> or = 85 points), 5/25
      (20%) good results (> or = 70 points), 1 (4%) fair result (> or = 55 points and 1
      (4%) bad result (< 55 points). The retrograde intramedullary nailing makes a
      biological osteosynthesis of distal femoral fractures possible. Also in our aged
      patients good functional results could be obtained. Poor hold of the distal
      interlocking screws and difficult interlocking are the 2 major technical problems
      encountered with this implant. Early weight bearing is not advisable.

PMID- 9606852
TI  - [American football injuries in the German Federal League: risk of injuries and
      pattern of injuries].
AB  - This prospective study investigated the incidence of injuries in German
      Bundesliga football based on an evaluation of 2 American football teams in the
      season and pre-season 1995 to 1997. Certified team physicians and team
      physiotherapists were the initial medical professionals providing on-site
      diagnosis, injury documentation and first treatment of all injuries. An injury
      was defined as minor injury (group I) causing a missing of practice or game up to
      1 week, as severe injury (group II) causing a missing of practice or game for
      more than 1 week or hospitalisation and as fatal injury (group III) if the
      incident lead to treatment in an intensive care unit or remaining neurological or
      orthopaedical disability or death. Data were collected so that it was possible to
      calculate the risk of injury per time of exposition per athlete. The function of
      the athlete, influences of the weather and the mechanisms of the injuries were
      registered. Overall 713 injuries were documented. The rate of injury was
      calculated as 15.7 per 1000 hours of practice and game per athlete. Severe
      injuries with a loss of practice participation of more than 1 week were found in
      94 cases. Fatal injuries were not seen in the period of the study. The knee was
      found to be the most common site of injury, the ankle ranked second. Our study
      showed that the risk of injury in American football in German Bundesliga is
      comparable with soccer or handball.

PMID- 9606853
TI  - [Attempted suicide--a challenge for the trauma surgeon?].
AB  - The data from 767 patients after a suicide attempt or suicide were analyzed
      retrospectively. Skeletal damage was present in 52% of the patients. This was
      also the highest percentage in the breakdown of the injury patterns, followed by
      damage of the central nervous system (26.6%). Injuries to parenchymatous organs
      (20.1%) took third place. Extensive soft tissue injuries were diagnosed in 18.1%
      and relevant vascular lesions in 16% of suicide cases. At the same time, the high
      percentage of multiple trauma patients (22.9%) reflects the severity and the
      extent of injuries suffered in the application of "violent methods". Injuries of
      suicide cases involving violence often resemble those of serious road traffic
      accidents. In contrast to unselected patients, the injury pattern of suicide
      cases with multiple trauma is dominated by jumps from a great height and being
      run over by a train. However, when unusual suicide techniques are used, the
      surgeon's experience may soon become insufficient. To our knowledge, special
      traumatology wards provide the best available diagnosis and emergency care for
      these patients unless they have suffered purely trivial injuries.

PMID- 9606854
TI  - [Self-mutilation as insurance fraud].
AB  - The case of a self-amputation of the left-sided forefinger is presented. It was
      an isolated smooth amputation near the basic ankle of the finger without any
      accompanying injury of other fingers. The victim (a physician) claimed financial
      compensation from his accident-insurance; his contract included special
      disability taxes for finger injuries. However, the insurance company did not pay
      but was able to demonstrate--by means of a medico-legal reconstructive expertise-
      that the amputation was voluntary and self-inflicted. The argumentation
      concerning self-mutilation is presented (including the so-called execution
      position of the finger and ergonometric aspects). Concerning the surgical care,
      intervention and diagnostic procedures a detailed documentation of the case
      history and the morphology of the injury pattern are recommended (especially in
      isolated finger-amputations of the non-working hand.

PMID- 9606855
TI  - [Bilateral pertrochanteric spontaneous fracture in chronic alcoholism and liver
      cirrhosis. A case report].
AB  - Fractures of the neck or the pertrochanteric region are often treated with
      dynamic hip screw especially in elderly patients. We give a case report covering
      treatment and follow-up for a bilateral spontaneous pertrochanteric fracture in a
      45-year-old man as a result of hepatogenetic osteopathy.

PMID- 9606856
TI  - [Urgent issues of nutrition improvement and public health of Russian population:
      concept of state policy in the field of healthy nutrition of Russian population
      for the period up to the year 2005].

PMID- 9606857
TI  - [On the federal law "Food safety in Russian Federation"].

PMID- 9606858
TI  - [Evaluation of energy metabolism of women working at the silk weaving factory,
      Dushanbe, Tajikistan ].
AB  - Evaluation of energy expenses and energy needs of the 19-23 years old women was
      carried out. It was shown average energy expenses of women-weavers were 2035 kkal
      per day. The professional activity accounts for 25.2% of all energy expenses,
      sleep--24.6% and other kinds of activity--34.2%.

PMID- 9606859
TI  - [Biologically active food additive from mussels].
AB  - Acid mussel hydrolisate MIGI-K LP is a food product, and a medical and
      prophylactic preparation containing a full set of irreplaceable amino acids (with
      the exception of thriptophane), essential fatty acids, macro- and microelements.
      MIGI-K LP can be used as a foot additive which improves the taste and increases
      the food qualities of the product, and as a medical preparation against some
      diseases.

PMID- 9606861
TI  - [Topinambur, and its use in pediatric diet therapy].

PMID- 9606860
TI  - [Effect of vitamin D metabolites on the markers of protein, calcium and
      phosphorus turnover in children with chronic renal failure].
AB  - Amino acid analysis and investigation of nitrogen, calcium and phosphorus balance
      were done in two groups of the patients with renal failure and osteodystrophy on
      the Vitamin D metabolites and analogues treatment. The results of the
      investigation confirm vitamin D metabolites influence on free amino acid turnover
      and on nitrogen, calcium, phosphorus balance. We observed significant decreases
      of blood amino acids and good influence on renal osteodystrophy in patients
      treated with the vitamin D metabolites. Vitamin D metabolites didn't influence on
      the retention, urinary and fecal excretion of endogenous nitrogen in patients
      with renal failure.

PMID- 9606862
TI  - [Dietary intake of different forms of iron and other factors of anemia
      epidemiology in women of childbearing age in S. Petersburg].
AB  - Actual nutritional status and dietary intake of different iron forms of the women
      in Sankt-Peterburg were investigated. The concentration of blood hemoglobin was
      studied. Signs of deficiency of nutrition of the investigated women were not
      found both by analysis of foodstuffs and energy intake and by anthropometric
      estimation of nutritional status.

PMID- 9606863
TI  - [Effect of diet therapy on metabolism of prostaglandins in patients with
      hypertension and obesity].
AB  - Significant disturbances of immune regulation of prostaglandine metabolism were
      found in patients with hypertension and obesity. Use of antisclerotic diet with
      low sodium contents promoted positive changes of clinical symptoms of diseases,
      in particular normalizations of process of immune regulation of prostaglandine
      metabolism connected with formation of natural antibodies.

PMID- 9606864
TI  - [Dietary supplements from ground fish meat with DNA for treatment and
      prophylaxis].
AB  - It has been developed a receipt of a new treatment-and-prophylactic products
      based on fish farce with treatment-and-prophylactic additive--DNA. It is
      recommended to be produced. As biological active additive keeps its initial
      pharmacological characteristics under technological processing this product is
      recommended for rendering general effect and increasing of physical and mental
      activity of organism.

PMID- 9606865
TI  - [Prophylactic syrups for population of environmentally polluted areas].
AB  - The formulas and manufacture technology of the prophylactic syrups for population
      living in zones of radioactive pollution were developed. The basic raw material
      for syrups were infusions of herb having various radioprotective properties. As
      additional raw material was used food supplement "Adaptin".

PMID- 9606866
TI  - [Using winegrowing products in sanatorium treatment].
AB  - Treatment of patients by products a viticulture (raisins, grape juice, dry red
      wine) simultaneously with traditional resort procedures was studied. Essential
      optimization of psycho-physic state of all examined groups was found. The level
      of increase of investigated parameters depend on a kind of products a viticulture
      and initial level of investigated parameters. The largest level of optimization
      of psycho-emotional state was revealed at the prescription dry vine. It was
      increased on 91.2% in relation to a background level. Age factor didn't influence
      on extent of increasing of optimization level.

PMID- 9606867
TI  - [Dietary fibers in diet therapy].
AB  - Dietary fibers belong to the group of polymeric compounds with different chemical
      origin. They play an important part in functioning of number of organs and body
      systems and in the first place influence upon the function of large intestine.
      Having ability to retain water, they accelerate an intestine transit and
      peristalsis of large intestine, and are the stool forming factor. Dietary fibers
      adsorb many bile acids, metabolites, toxins and electrolytes and promote
      detoxification of organism. Due to ionchange properties dietary fibers are
      capable to remove ions of heavy metals and radionuclides. Dietary fibers render
      positive action during the functional diseases of large intestine, reduce blood
      cholesterol concentration, have hypolipidemic effect and can be used for
      prophylactic and therapy of cardiovascular and other diseases.

PMID- 9606868
TI  - [To improve certification system].

PMID- 9606869
TI  - [Epidemiology of obesity].

PMID- 9606870
TI  - [Viral hepatitis C and G (Hepacivirus, Flaviviridae): etiotropic therapy].

PMID- 9606871
TI  - [Epidemiologic features of influenza in past years].

PMID- 9606872
TI  - [HTLV-I as a carcinogenic factor and instrument for studying the migratory
      history of ancient man].

PMID- 9606873
TI  - [Characteristics of experimental models of hepatitis A in Papio hamadryas].
AB  - Hepatitis A (HA) was induced in 14 Papio hamadryas by strain VHA-PH isolated from
      this species of monkeys with spontaneous infection, strain VHA-MM isolated from
      Macaca mulatta, and a unique strain VHA-H3 isolated from a patient; this latter
      strain is pathogenic for Macaca mulatta in experiment. All infected seronegative
      animals developed a disease with virological, serological, biochemical, and
      morphological signs characteristic of human HA, but the duration of these signs
      manifestation varied. Virus in the feces and an increased level of SGPT were
      detected periodically starting from days 3-26 to 24-135, and in 4 monkeys even
      later (up to days 163-238). Morphologic changes in the liver, typical of acute
      hepatitis, were observed from days 10-46 to days 16-130. Strain VHA-H3 is less
      pathogenic for papios. HA models on Papio hamadryas infected with strains VHA-PH
      and VHA-MM can help solve many research and practical problems.

PMID- 9606874
TI  - [Kama, a new virus (Flaviviridae, Flavivirus, Tiulenii antigenic group), isolated
      from Ixodes lividus ticks].
AB  - Three identical strains of a new virus Kama (Flaviviridae, Flavivirus, Tyuleny
      antigenic group) were isolated from Ixodes lividus Roch, obligate parasites of
      Riparia riparia L. The ticks were collected in June, 1990 in Tatarstan on the
      islands in the basin of the Kama river. The strains were examined under electron
      microscope and by serological tests (neutralization, complement fixation,
      hemagglutination inhibition, and indirect immunofluorescence). The virus is
      antigenically related but not identical to Tyuleny virus. Hence, the Tyuleny
      antigenic group at present includes viruses Tyuleny, Meaban, Gadgest Gally,
      Saumares Reef, and Kama. All these viruses are associated with an ecosystem
      including ixodide ticks, obligate parasites of colonial birds.

PMID- 9606875
TI  - [Reproduction and synthesis of proteins from human adenovirus serotype 4].
AB  - Multiplication and protein synthesis of type 4 human adenovirus (Ad 4) were
      investigated. Immunofluorescence patterns (diffuse and distinct spot nuclear
      fluorescence) of hexon and process ad 4 were different when monoclonal antibodies
      to these proteins were used. Mature antigen-active capsid and core proteins were
      detected by Western blotting at different periods postinfection. Ad 4 effectively
      multiplied in human cells HeLa and A549, less so in monkey cells (Vero), and
      poorly in murine cells (L, BF(Balb). The synthesis of structural virus proteins
      was suppressed in murine cells and little changed in simian cells. DNA-binding
      protein has molecular weight of 50,000 daltons at Ad 4 infection of Vero cells as
      against 72,000 daltons in infected L and HeLa cells.

PMID- 9606876
TI  - [Connection between Epstein-Barr virus infection and HLA phenotype and features
      of cytokine status in patients with non-Hodgkin's lymphomas].
AB  - Thirty-four primary (untreated) patients with non-Hodgkin's lymphomas (NHL)
      infected with Epstein-Barr virus (EBV) were examined. Their HLA phenotype and the
      production of interleukin-1 beta and tumor necrosis factor alpha were assessed.
      Serological profiles characteristic of the late stages and reactivation of EBV
      infection were detected in 16 (47.1%) patients. NHL of low malignancy
      predominated in EBV-infected patients. A greater number of blank HLA-A antigens
      and a higher incidence of HLA-DR7 antigen was observed in infected patients.
      Serum concentration of tumor necrosis factor alpha was reliably higher in them,
      whereas the production of this cytokine by the peripheral blood mononuclears
      decreased. Hence, serum tumor necrosis factor is a product of transformed B
      lymphocytes. Spontaneous and stimulated production of interleukin-1 beta by
      peripheral blood mononuclears was significantly decreased in EBV-infected
      patients, and the serum concentration of this cytokine similarly had a trend to
      decrease, which indicates an inhibition of interleukin-1 beta production in EBV
      infected patients with NHL.

PMID- 9606877
TI  - [Evaluation of antiviral activity of new medicinal forms of foscarnet in genital
      herpes in guinea pigs].
AB  - Antiviral activity of a Russian drug foscarnet (tablets and coated pills) was
      assessed in guinea pigs with experimental genital herpes. New dosage forms were
      well tolerated by the animals, causing no manifest symptoms of intoxication
      irrespective of the doses or protocols of the drug use, Foscarnet in any dosage
      form in the total daily dose of at least 120 mg/kg had a pronounced antiviral
      effect towards herpes simplex type II virus, comparable with that of the
      commercial reference drug virolex: the intensity of clinical symptoms was
      alleviated and the disease duration shortened.

PMID- 9606878
TI  - [Physico-chemical bases of the mechanism of thermal inactivation of the foot-and
      mouth disease virus].
AB  - Experiments demonstrated that the effect of water activity on the solvate complex
      of virions underlies the mechanism of thermal inactivation of the foot and mouth
      disease virus in suspension; changes in the structure of the complex impair the
      electrophysical balance of the RNA-protein relations and hence, destroy the
      virus. Heating of virus-containing suspensions at moderate positive temperatures
      leads to destruction of the noninfectious part of virus population of 146S
      particles, thus decreasing the infectious activity of the virus.

PMID- 9606880
TI  - [Fungi in the intestine--normal flora or pathogens?].
AB  - Candida spp. und C. albicans are common within the microbial ecosystem of the
      human orointestinal tract. Candida in low quantities is found at various sites in
      healthy subjects. In patients with typical risk factors, mainly in
      immunocompromised hosts, an increased growth of Candida occurs. In cases with
      multiple sites colonised there will be an increased risk of severe Candida
      infections. The metabolic activity of Candida in the gut is very low under
      anaerobic condition and limitation of nutrients.

PMID- 9606879
TI  - [Polymerase chain reaction in diagnosing cytomegalovirus infection in HIV
      infected patients].
AB  - The authors propose a simple and standard approach to semi-quantitative detection
      of cytomegalovirus (CMV) DNA in blood leukocytes by the polymerase chain
      reaction. The method was used in early diagnosis and treatment of manifest CMV
      infection in HIV-infected patients. High titers of CMV DNA correlated with the
      manifestation of CMV disease and progressive loss of host immune function.
      Clinical significance of difference in DNA titers was revealed. The proposed
      method can be used to assess the efficacy of specific anti-CMV therapy.

PMID- 9606881
TI  - [Fungi in the oro-intestinal tract and their scientifically founded status].
AB  - The orointestinal tract is a reservoir for facultatively pathogenic fungi,
      especially Candida albicans. In all of its sections in immunocompromised hosts,
      the occurrence of a mucosal mycosis is possible which may be the starting point
      of an infection of internal organs. The mouth and esophagus are the most often
      affected locations. A synopsis of clinical (including endoscopic) findings,
      mycological cultivation and mycoserology is important in diagnostics. There is no
      connection between the incidence of Candida in the orointestinal tract and
      multiple local symptoms like fatigue, headache, heartburn and others called
      "candidiasis hypersensitivity syndrome" or "mycophobia".

PMID- 9606882
TI  - [Candida infections in infancy and early childhood].
AB  - Candida infections in infancy can manifest themselves as skin, mucosal or
      systemic candidiasis. Eighty to nintey percent of all candida infections in this
      age group are caused by Candida albicans. Whereas in neonates, infections mostly
      occur sub partu, in older children predisposing underlying diseases get an
      increasing etiological importance. The diagnosis is based on microscopic and
      cultural detection of yeast as well as on the course of the titers of Candida
      antigen and antibodies. For topical antifungal treatment of skin and mucosa
      infections, different preparations of the polyenes nystatin and amphotericin B
      have been proven to be most effective. In systemic candidiasis the combination of
      amphotericin B and 5-flucytosin is the treatment of choice. In view of the
      potential severe side effects of this combination therapy, fluconazol as a sole
      treatment represents an effective alternative. Prophylaxis against Candida
      infections comprises sticking to hygienic regimes, mycological surveillance of
      risk groups and oral application of antimycotics.

PMID- 9606883
TI  - [Early detection and diagnosis of invasive mycoses].
AB  - An invasive mycosis may cause death in high-risk patients. An early systemic
      antimycotic therapy can save life. Therefore, a continuous mycological monitoring
      in one week intervals is necessary in high-risk patients beginning with the day
      of admission. This monitoring should be done three to five times a week when an
      organ manifestation is suspected. Due to the continuous monitoring, the
      assignment of the results is much easier for the clinician. The goal of the
      mycological monitoring is to obtain an early hint of a fungus infection. The
      results of the culture as well as serum titers of antigen and antibodies have to
      be interpreted in connection with the clinical picture of the underlying disease
      and the actual risk of infection. Negative results do not rule out a mycosis!
      Positive results do not always proof an invasive mycosis. Only by interpreting
      the time course of the mycological findings and the patient's clinical status, an
      invasive mycosis may be diagnosed with some certainty. In any case, additional
      procedures like radiological techniques (i.e. CT-scan), histology etc. should be
      used.

PMID- 9606884
TI  - [Vulvovaginal mycoses].
AB  - Due to its pathogenety Candida albicans is the most frequent yeast in cases of
      vaginal candidosis, probably mostly caused by local immunological weakness. In 5
      30% one can expect a vaginal yeast colonisation depending on age, estrogen
      influence, pregnancy and dispositions by illness. Prepartal vaginal yeast
      colonisation should be treated to protect the newborn. The only typical symptom
      of acute vaginal candidosis is itching. Beside history and clinical symptoms,
      examination of vaginal secretion by phase contrast microscopy and the yeast
      culture are cornerstones of the diagnosis. Antimycotic resistance should be
      investigated only by specialists. Acute Candida albicans vaginitis should be
      treated locally by one or three day therapy. Candida glabrata vaginitis can be
      treated with high doses of oral fluconazole.

PMID- 9606885
TI  - [Tinea in glabrous skin: total quality management].
AB  - Today tinea of glabrous skin still is one of the central diagnostic and
      therapeutic problems in dermatology. The choice of the adequate treatment is
      always influenced by the type of microorganism, the site of manifestation, time
      course and severity of the infection as well as by the immune status of the
      patient. Tinea has to be differentiated from other skin diseases. Thus, general
      guide lines for diagnostic processing are needed. Adequate treatment with various
      types of antimycotics either is topical or--less frequently--systemic.

PMID- 9606886
TI  - [Diagnosis, differential diagnosis and therapy of onychomycosis].
AB  - Onychomycosis is a common infectious disease. The diagnosis always requires proof
      of the presence of fungi by culture. Nail psoriasis and onychodystrophy of
      another origin are clinically very similar to onychomycosis. There is a choice of
      topical and systemic antimycotics available for treatment. The modern antimycotic
      nail lacquars are well suited for the treatment of distal onychomycosis. If more
      than 2/3 of the nail plate and/or the nail matrix are infected, the treatment
      must be systemic. There is a choice of griseofulvin, terbinafine and
      itraconazole.

PMID- 9606887
TI  - [Checklist for methodological quality of guidelines. A contribution to quality
      promotion of medical guidelines].
AB  - The society of physicians of Germany and the society of panel physicians laid
      down in the "assessment criteria for guidelines in medical care" what kind of
      demands the medical selfadministration makes on guidelines. This measure also had
      the goal to support and strengthen the efforts of the AWMF for guidelines of high
      value. On the basis of these assessment criteria, a tool was compiled for the
      systematic registration and documentation of quality criteria for good guidelines
      for the first time in areas of German language. This check list is guided by the
      structure and content of the "Criteria for Appraisal for National Guidelines" by
      the Scottish Intercollegiate Guidelines Network.

PMID- 9606888
TI  - [Clinical, diagnostic and pathogenetic aspects of reflux-associated cough].
AB  - Gastroesophageal reflux may be responsible for atypical extra-esophageal
      symptoms, such as chest pain, dyspnea, chronic cough, or hoarseness. Prospective
      studies of gastroesophageal reflux have indicated reflux as the cause for chronic
      cough in 10 to 20% of patients. The precise mechanism by which reflux causes
      cough remains uncertain, although the possibility that the cough is caused by
      stimulation of the esophageal mucosa receptors rather than aspiration is
      suggestive from some studies. Prolonged esophageal pH monitoring affords an
      opportunity to document objective gastroesophageal reflux. Furthermore, pH
      monitoring gives the opportunity to correlate temporally acid reflux events with
      the onset of certain symptoms.

PMID- 9606889
TI  - [Critique of continuing medical education from the viewpoint of participants.
      Results of an evaluation of didactic seminars of the Academy of Continuing and
      Graduate Medical Education of the Hessen Federal Association].
AB  - In cooperation with the chair of academy of vocational training and educational
      planning of the University of Technology Darmstadt the academy planned and
      realized a systematic evaluation concerning participants's opinion and criticism.
      A half-standardized questionnaire was developed, tested and applied according to
      the rules and recommendations of the German medical association. Between 9/94 and
      11/98, feedback from 121 of the academy's seminars was received. Most seminars
      were judged positively in view of clarity and stimulation of thoughts while there
      was considerably less praise for the contribution of self-information and the
      possibilities of communicating and interacting. With regard to the lecture's
      practical relevance most seminars were judged positively. Media design and
      management was considered insufficient by most of the participants, as were time
      management and pre-information. The idea of examining the effect of learning was
      rejected by most of the students: Better media were desired, as were more case
      studies and literature references.

PMID- 9606890
TI  - [Quality management in the hospital].
AB  - Quality management in hospitals is a much discussed topic. However, mainly
      theorists take the floor, who have some good advice, but rarely have practical
      experience. All those theorists have been heard by the responsible person of the
      Fritz-Konig-hospital in Bad Harzburg, as well. At the end, however, an own system
      of quality management was developed with the aid of an external expert. This
      article describes the step-by-step introduction of quality management and the
      related experiences.

PMID- 9606891
TI  - [Brain decade: achievements of neurology].

PMID- 9606892
TI  - [Systemic organization of brain functions: key role of results action acceptor].
AB  - The paper presents general principles of organization of human psychic functions
      on the basis of P.K.Anokhin's theory of functional systems. The peculiarities of
      forming psychic activity are analyzed on the information basis of systemic
      activity of brain. The key role in management of psychic activity belongs to
      foreseeing of required results, i.e. the acceptor of action's results.
      Holographic and molecular mechanisms of forming informative engram of acceptor of
      action's results are considered.

PMID- 9606893
TI  - [State of autonomic regulation mechanisms in arterial hypotension].
AB  - To investigate the role of suprasegmental and segmental parts of autonomic
      nervous systems (ANS) in genesis of arterial hypotension (AH) 75 individuals with
      arterial hypotension as well as 30 healthy persons were examined using clinical
      and psychological methods, evaluation of the state of ANS segmental part by means
      of evoked skin sympathetic potentials, spectral analysis of the variability of
      the heart rhythm, 5 standard cardiovascular tests according to Ewing. The
      conclusion was made that individuals with AH had combination of alterations of
      both emotional-personality sphere and autonomic functions in all systems of
      organism tested. Exactly they had psychoautonomic syndrome presenting as
      combination of asthenic manifestations, elements of Reynaud phenomenon and
      headaches pronounced differently (headaches of tension more frequently). Clinical
      alterations were combined with changes of indices of functional testing, that
      reflected disorders in some link of sympathetic regulation including baroreflex
      one. Decompensation in individuals with AH and change for the worse of the
      indices of functional testing were due both to the increase of psychoautonomic
      disorders, growing of desintegrational processes in ANS and the decrease of
      adaptive mechanisms in its sympathetic part.

PMID- 9606894
TI  - [Disorders of sleep structure and autonomic regulation in sleep of patients with
      stroke].
AB  - Peculiarities of both the structure of night sleep and autonomic regulation in
      the sleep were studied in 30 patients with ischemic stroke of different location.
      Clinical, polysomnographic (including autonomic indices) and psychologic methods
      were used. Considerable alterations in the structure of night sleep were
      observed, namely: lengthening of the period of falling asleep, increase of the
      time of awakening inside the sleep, impossibility to support necessary duration
      of both stages and phases of sleep. The indices of cardiovascular system's
      activity such as heart rate (HR) and arterial pressure (AP) were altered most of
      all. The most dramatic disorders of both the structure of sleep and autonomic
      regulation in the sleep were found in right hemispheric and medial location of
      ischemic stroke. High values of HR and AP in the sleep (especially in phase of
      the fast sleep), high HR and AP variability as well as the decrease of these
      indices from the first cycle of the sleep to the third one were prognostically
      unfavourable factors.

PMID- 9606895
TI  - [Trigeminal evoked potentials in migraine].
AB  - Trigeminal evoked potentials (TEP) were studied in 19 patients with migraine
      without aura. Significant shortening of latent periods of early and late TEP
      components was observed during stimulation on the side of headache as compared
      with the same indices during stimulation on nonalgesic side. Hyperreactivity of
      trigeminal vascular system in patients with migraine without aura during the
      period between the attacks is discussed. Asymmetry of laten TEP periods may
      determine the preferential side of headache, on the one hand, and may reflect the
      changes in trigeminal system following the repeated lateralized fits of migraine,
      on the other hand. Administration of 1 g of aspirin resulted in increase
      (normalization) of the latentions of TEP components. After efferalgan
      administration TEP changes were not registered. The suggestion is made that
      inhibitory influence of aspirin on the truncal trigeminal system is one of the
      central mechanisms of its action.

PMID- 9606896
TI  - [Clinical picture of schizophrenia with melancholic depression].
AB  - 75 patients were observed. Variants of the disease were identified which differed
      by premorbid state, age of both onset and manifestations of the disease, number
      of attacks, their psychopathologic structure and duration of melancholic
      depression as well as by changes of personality. The disease coursed as shift
      like progredient schizophrenia with bipolar disorders in structure of pure
      affective attacks, shift-like progredient schizophrenia with monopolar
      depressions in structure of affective attacks, shift-like progredient
      schizophrenia with affective and affective-delirious attacks, intermediate
      variant of the disease between manic-depressive psychosis and shift-like
      progredient schizophrenia.

PMID- 9606897
TI  - [Depressive states in adolescents with epilepsy].
AB  - 11 adolescents at the age from 14 to 17 years with epilepsy were observed.
      Depressive states (27 ones) arose in such patients in the course of the main
      disease. It has been established that the depressive states in epilepsy can be
      caused by both the epileptic illness itself and psychic trauma. The following
      depressive syndromes were described: anxious, depressive-dysphoric, simple
      (melancholic), anergic. Depressions were atypical in terms of manifestations of
      the separate components of depressive triad, daily changes of the mood, etc. The
      depressive states appearing in the course of epilepsy can proceed on both the
      psychotic and neurotic level. The depressive states of the psychotic level can be
      found more often within the general framework of the polymorphous psychotic
      syndrome (so-called "schizoepilepsy" type). The latter was observed in 7
      patients. The therapeutic recommendations are given.

PMID- 9606898
TI  - [Treatment of fibromyalgia].
AB  - The paper reports the results of therapy of 23 patients with fibromyalgia (FM).
      Tetracyclic antidepressant lerivon, was administered to group 1, nonsteroid
      antiinflammatory (NSAI) preparation nurofen to group 2 and phototherapy (exposure
      to bright white light) was used in group 3. Clinical effect in the form of a
      decrease of both the intensivity of algesic syndrome and autonomic manifestations
      as well as improvement of night sleep were clearly seen in group 1.
      Manifestations of both anxious and depressive disorders were less pronounced.
      Treatment by Nurofen resulted in slight decrease of intensivity of pains but
      didn't lead to pronounced alterations of emotional sphere. Administration of
      either Lerivon or Nurofen promoted the increase of pain thresholds (according to
      the data of nociceptive flexory reflex). The data obtained testified the
      necessity of complex therapy of FM patients including administration of
      antidepressants and analgetic drugs of NSAI group. Dynamic polysomnographic
      examination of patients from group 3 revealed the increase of total sleep
      duration, decrease of the time of falling asleep, the latent period of the phase
      of the fast sleep, activated movement index, intensivity of movements and the
      time of being awake in the sleep. The conclusion was made that it was worth while
      to use phototherapy as alternative, nonmedicine method of phothotherapy.

PMID- 9606899
TI  - [Acetylsalicylic acid in therapy of migraine].
AB  - The paper reports the results of preventive therapy of 105 patients with migraine
      without aura by acetylsalicylic acid in doses 1000, 500 and 100 mg (in 3 groups
      of patients). The data were presented about the efficiency of these schemes of
      treatment as well as about the predictors and contra-indications for their
      prescription. Central and peripheral mechanisms of drug's action were considered.

PMID- 9606900
TI  - [Effectiveness of fluoxetine (portal) in atypical depressions].
AB  - Efficiency of fluoxetine (one of the selective serotonin reuptake inhibitors) was
      examined in the course of treatment of 24 patients with atypical depressions that
      were characterized by prevalence of either negative (12 patients) or positive (12
      patients) affectivity. Fluoxetine was more effective in patients with domination
      of negative affectivity (apathias, angedonias, alexithymias). Total efficiency of
      fluoxetine was equal to 91% in group with prevalence of negative affectivity and
      41% with prevalence of positive affectivity. In the latter group the side-effects
      were more pronounced that resulted in prescription of corrective therapy.

PMID- 9606901
TI  - [Cytogenetic and molecular genetic diagnostics of Rett syndrome in children].
AB  - Rett syndrome in 32 children (31 girls and 1 boy) was diagnosed according to
      International association on Rett syndrome. The phenomenon of the presence of
      special type of late-replicating chromosome X (type C) was revealed. This
      phenomenon may be recommended as a diagnostic test for both preclinical periods
      of development of the disease and in atypical cases of Rett syndrome.

PMID- 9606902
TI  - [Family and epilepsy].

PMID- 9606903
TI  - [Vascular parkinsonism].

PMID- 9606904
TI  - [Rare observation of schizophrenic patient with inclination to swallow foreign
      bodies].

PMID- 9606905
TI  - A review of the possible bacterial determinants of clinical outcome in
      Helicobacter pylori infection.
AB  - Helicobacter pylori is present in 40-60% of the population and approximately 10
      20% of these infected individuals suffer from a H. pylori associated disease such
      as peptic ulcer disease or gastric cancer. This article reviews the potential
      bacterial determinants responsible for and markers predictive of both the
      acquisition of H. pylori infection and subsequent clinical outcome; i.e.,
      asymptomatic infection or disease. The acquisition of H. pylori infection depends
      on exposure (hence the increased risk in lower socioeconomic groups and
      developing nations) to viable bacteria with at least a functional urease gene in
      a susceptible host. Once infection occurs, bacterial virulence factors, including
      the vacuolating cytotoxin, and genes of the cag pathogenicity island, as well as
      nonbacterial factors may determine disease outcome. Future research is being
      directed at discovering other bacterial virulence factors responsible for the
      different clinical outcomes of H. pylori infection. This will be greatly enhanced
      by the recent release of the complete genome sequence of H. pylori. The
      determination of the relative importance of each of these recognized and other as
      yet unrecognized factors responsible for disease outcome will assist in the
      appropriate targeting of patients in the treatment of H. pylori infection.

PMID- 9606906
TI  - Functional and structural successions in arbitrary samples of heterotrophic
      bacteria during aerobic treatments of lignite-carbonization wastewater in in situ
      enclosures.
AB  - In situ mesocosm experiments were performed in Lake Schwelvollert (located in the
      district of Weissenfels, Saxony-Anhalt, Germany), an anaerobic lignite
      carbonization effluent lake containing phenolic compounds and their autoxidation
      products (anthropogenic humic matter). In the aeration enclosure, the anaerobic
      Schwelvollert wastewater was aerated and in the flocculation enclosure, it was
      flocculated to precipitate the oxygen-trapping anthropogenic humic matter to
      enhance the input of oxygen by diffusion. To gain an insight into the metabolic
      state of the aerobic heterotrophic microbiota during the treatments, arbitrary
      samples of bacterial isolates were taken from a general agar medium and tested
      for their abilities to cleave predominant phenolic contaminants by a procedure
      called the isolate sample assay. In this way, successions of degradation
      potentials were observed in both mesocosms, with degradation abilities for meta-
      and para-alkylated phenols appearing before degradation abilities for ortho
      substituted phenols as a common phenomenon. To examine the structure of samples,
      the respective isolates were characterized using the Biolog GN MicroPlate system,
      the random amplified polymorphic DNA nucleic acid (RAPD) fingerprinting
      technique, and amplified ribosomal DNA restriction analysis (ARDRA). Although
      similar functional patterns occurred in both mesocosms, the compositions and
      diversities of the respective bacterial communities varied significantly, even at
      different depths from the same enclosure, with members of the Pseudomonas RNA
      group I being predominant.

PMID- 9606907
TI  - The Campylobacter fetus S layer is not essential for initial interaction with HEp
      2 cells.
AB  - In vitro adherence assays were used to determine whether the S layer mediated
      interactions between Campylobacter fetus subsp. venerealis strains and HEp-2
      cells. At multiplicity of infection ratios ranging from 0.1:1 through 100:1,
      quantitation of bacterial adherence by light microscopy revealed that S layer
      deficient isogenic C. fetus 809K and C. fetus 810K were not less efficient in
      their attachment to HEp-2 cells; either S layer deficient C. fetus strains
      interacted with HEp-2 cells in greater numbers than the corresponding wild-type
      parent strains 809 and 810 or there was no significant difference in adherence
      levels between wild-type and mutant strains. Adherence of C. fetus strains to HEp
      2 cells increased most during the first 2 h of a 22-h incubation period with only
      a slight increase in C. fetus cell numbers occurring subsequent to 2 h. At each
      assay point throughout this 22-h time period, equivalent numbers of wild-type and
      S layer deficient C. fetus strains were observed associated with HEp-2 cells.
      Prior to 2 h, adherence levels of all C. fetus strains exceeded those of
      Escherichia coli AB264 and Salmonella typhimurium SL1344. And, unlike S.
      typhimurium, C. fetus did not undergo significant replication following initial
      adherence to HEp-2 cells. Campylobacter fetus did not adhere to HEp-2 cells in a
      localized or aggregative pattern but were randomly distributed over individual
      HEp-2 cells and at no time during the assay with C. fetus were changes in HEp-2
      cell morphology apparent. These data suggest that the S layer is not essential
      for mediating initial interactions between C. fetus and HEp-2 cells.

PMID- 9606908
TI  - Expression of a Bacillus thuringiensis delta-endotoxin gene by Bacillus pumilus.
AB  - The delta-endotoxin genes from Bacillus thuringiensis were introduced into a
      rhizosphere-inhabiting Bacillus pumilus isolate to create a delta-endotoxin
      expression and delivery system for subterranean feeding insects such as the
      larvae of pale western cutworm (Agrotis orthogonia Morrison (Lepidoptera:
      Noctuidae)). Preliminary experiments indicated that Bacillus thuringiensis subsp.
      kurstaki cultures were toxic to pale western cutworm larvae. Three different cry
      genes from Bacillus thuringiensis subsp. kurstaki were cloned into high and low
      copy number vectors and mated into Bacillus pumilus RB8. When carried on high
      copy number vectors, cry genes appeared to inhibit sporulation and delta
      endotoxin production in Bacillus pumilus RB8 cultures, since microscopic
      examination of these cultures revealed that < 0.1% of the cells of late
      stationary phase cultures had sporulated and produced parasporal inclusions. On
      low copy number vectors, the cry genes did not inhibit sporulation; however,
      production of delta-endotoxins was undetectable. Using a heat shock regime for
      enrichment of sporogenous crystalliferous variants, a Bacillus pumilus isolate,
      carrying cryIA(c) on a high copy number plasmid, was obtained in which high level
      delta-endotoxin production occurred concomitant with sporulation. Synthesis of
      functional delta-endotoxin by this strain was confirmed by Western blot analysis
      and bioassay with pale western cutworm larvae. These results show that
      rhizosphere-inhabiting bacilli are indeed a potential route for introduction of
      delta-endotoxins to the root environment for biocontrol purposes.

PMID- 9606909
TI  - Degradation of hydrocarbons in crude oil by the ascomycete Pseudallescheria
      boydii (Microascaceae).
AB  - Four unique strains of Pseudallescheria boydii were isolated from oil-soaked
      soils in British Columbia and Alberta and compared to strains from cattle dung
      and raw sewage. Considerable variability in morphology, colony appearance, colony
      diameter, and temperature tolerance occurred among the strains. They also varied
      in the sporogenous states produced in culture; all strains had a Scedosporium
      anamorph and either the Graphium anamorph or cleistothecial teleomorph.
      Conspecificity of the six isolates was inferred from their morphology and
      supported by restriction fragment length polymorphism profiles of the internally
      transcribed spacer region of rDNA and comparing these to Petriella sordida, a
      similar taxon in the Microascaceae. Three of the strains isolated from oil
      contaminated soil and the strain from sewage were tested for their ability to
      utilize hydrocarbons by incubation with Prudhoe Bay Crude oil as the sole carbon
      source. Gas chromatographic analysis of the residual oil revealed that the
      strains isolated from oil-contaminated soil degraded the linear aliphatics. The
      strain from sewage, previously shown by others to utilize the volatile n-alkanes
      (i.e., ethane, propane, and butane), did not utilize the liquid saturate
      compounds. None of the strains was observed to degrade compounds in the aromatic
      fraction. Pseudallescheria boydii may be an important agent for in situ
      bioremediation of saturates in oil-contaminated sites.

PMID- 9606911
TI  - Biodegradation of dibenzothiophene by a nodulating isolate of Rhizobium meliloti.
AB  - Rhizobium meliloti Orange 1 was isolated from aerobic sediments of a drainage
      ditch receiving oil refinery leakage. This bacterium has been shown to be capable
      of growing on dibenzothiophene as the sole carbon and energy source. This strain
      can also efficaciously nodulate alfalfa plants. In cultures with
      dibenzothiophene, Orange 1 produces six degradation intermediates. By means of
      analyses with UV-visible and GC-MS spectrometry, as well as nuclear magnetic
      resonance spectroscopy, three of these products were identified as 3-hydroxy-2
      formyl-benzothiophene (product A), benzothienopyran-2-one (product B'), and
      dibenzothiophene-5-oxide (product D). This suggests that R. meliloti Orange 1
      metabolizes dibenzothiophene via oxidative cleavage of the aromatic ring with a
      mechanism analogous to that described for naphthalene degradation.

PMID- 9606912
TI  - Simplified reverse transcription polymerase chain reaction procedure with
      detection by microplate hybridization for routine screening of hepatitis A virus.
AB  - Reverse transcription polymerase chain reaction, using either nested or
      seminested primers, is used extensively for the detection of viruses in small
      quantities. However, existing methods are prone to false positive reactions. We
      report here an improved polymerase chain reaction technique based on the use of
      longer primers (39 nucleotides) with single-step amplification, applied to the
      detection of hepatitis A in low quantities. While the sensitivity of this
      technique (10 x the 50% tissue culture infective dose) is equivalent to that of
      existing methods, it is a simpler procedure, less time consuming, and less
      susceptible to contamination and therefore provides a more reliable tool for
      routine diagnosis. Finally, the development of a DNA enzyme immunoassay detection
      technique and the complete automation of the procedure allow a large number of
      samples to be processed in clinical laboratories.

PMID- 9606913
TI  - Aminopeptidase activities in Peptostreptococcus spp. are statistically correlated
      to gelatin hydrolysis.
AB  - One hundred Peptostreptococcus isolates from five species were assessed for their
      ability to hydrolyze gelatin. Most Peptostreptococcus magnus (95.8%) and
      Peptostreptococcus micros isolates (79.0%) hydrolyzed gelatin in contrast to
      Peptostreptococcus asaccharolyticus (8.0%), Peptostreptococcus anaerobius
      (10.0%), and Peptostreptococcus prevotii isolates (16.7%). Gelatin hydrolysis in
      Peptostreptococcus magnus and Peptostreptococcus micros isolates correlated (r =
      0.80; P = 0.0019) with more aminopeptidases produced than Peptostreptococcus
      asaccharolyticus, Peptostreptococcus anaerobius, or Peptostreptococcus prevotii.
      The five species were further classified into three groups using the extended
      Tukey test (P < 0.0001) based on the mean percentage of aminopeptidases produced
      by each species with Peptostreptococcus magnus and Peptostreptococcus micros
      belonging to group I, Peptostreptococcus asaccharolyticus and Peptostreptococcus
      prevotii belonging to group II, and Peptostreptococcus anaerobius forming group
      III. An analysis of possible proteolytic activity of four selected
      Peptostreptococcus magnus isolates indicated that only 5 of 11 substrates were
      hydrolyzed as compared to a control isolate of Porphyromonas gingivalis W83,
      which had a strong proteolytic profile. Therefore, gelatin hydrolysis by
      Peptostreptococcus spp., in particular Peptostreptococcus magnus and
      Peptostreptococcus micros, is probably due to a variety of aminopeptidases rather
      than proteinases.

PMID- 9606914
TI  - Interaction between the pili of Pseudomonas aeruginosa PAK and its carbohydrate
      receptor beta-D-GalNAc(1-->4)beta-D-Gal analogs.
AB  - Pseudomonas aeruginosa employs pili to mediate adherence to epithelial cell
      surface receptors. Previously, it has been shown that the pilus adhesin of P.
      aeruginosa PAK binds to the ganglioside asialo-GM1. In particular, it was found
      that the carbohydrate sequence beta-D-GalNAc(1-->4)beta-D-Gal is the minimal
      carbohydrate receptor sequence of asialo-GM1. To study the binding specificity of
      P. aeruginosa, O-modified and N-modified sugar analogs, where each hydroxyl group
      was substituted either by O-methyl or O-propyl and the acetamido group was
      changed to a propionamido group, were synthesized. The sugar analogs were
      evaluated as inhibitors in a competitive solid phase binding assay. The results
      demonstrate that the pili of P. aeruginosa PAK accepts a variety of sugar analogs
      possessing the sequence beta-D-GalNAc(1-->4)beta-D-Gal. Most sugar analogs bind
      with a similar order of magnitude (50% inhibitory concentration (IC50) = 60-130
      microM) except for the 2-O-propyl derivative 7 (IC50 = 8 +/- 4 microM) compared
      with an IC50 of 79 +/- 18 microM for the native compound. The significant
      increase in binding affinity of 2-O-propyl derivative 7 suggests that improved
      inhibitors of adhesion may be prepared by introducing a hydrophobic side chain at
      the 2-position of galactose.

PMID- 9606915
TI  - Cleanup procedure for monitoring chlorinated compounds in animal feed and crops.
AB  - A powerful cleanup procedure for determination of chlorinated pesticides and
      polychlorinated biphenyls (PCBs) in difficult agricultural matrixes like feeds or
      crops was developed to eliminate the interferences in chromatograms obtained by
      gas chromatography with electron capture detection. The adsorption material used
      was ENVI-Carb, a graphitized nonporous carbon material. This procedure proved to
      be more reliable than the established cleanup procedure, which uses gel
      permeation chromatography and silica gel cartridges. Because ENVI-Carb cleanup
      delivers clear, colorless eluates with no interferences, chlorinated pesticides
      and PCBs may be detected at levels as low as 0.0004 mg/kg for monitoring
      purposes. Accuracy was validated through a series of recovery experiments.

PMID- 9606916
TI  - Determination of residues of flumequine and 7-hydroxyflumequine in edible sheep
      tissues by liquid chromatography with fluorimetric and ultraviolet detection.
AB  - A simple, sensitive, and rapid method for simultaneous determination of residues
      of flumequine and its microbiologically active metabolite 7-hydroxyflumequine in
      100 mg sheep edible tissues (muscle, liver, kidney, and fat) by liquid
      chromatography is reported. After liquid-liquid cleanup with ethyl acetate,
      tissue extracts were injected onto a Select B column. The 2 compounds were
      determined by ultraviolet and fluorimetric detection. The method was repeatable
      and reproducible for flumequine and 7-hydroxyflumequine in muscle, liver, kidney,
      and fat, with limits of detection below 2 and 3 micrograms/kg for flumequine and
      7-hydroxyflumequine, respectively. Mean recoveries for flumequine were 90 +/- 7,
      82 +/- 7, 89 +/- 5, and 82 +/- 6% in muscle, liver, kidney, and fat respectively.
      Mean recoveries for 7-hydroxyflumequine were 91 +/- 2, 90 +/- 4, 86 +/- 3, and 84
      +/- 4% in muscle, liver, kidney, and fat, respectively.

PMID- 9606917
TI  - Automated screening method for determining optimum preservative systems for
      personal and home care products.
AB  - A procedure was designed to determine the minimum preservative level (MPL) for
      personal and home care products. A highly preserved sample and an unpreserved
      sample were combined at different concentrations within a 96-well microtiter
      plate by using an autodilutor. A unique tip design made it possible to accurately
      deliver viscous test materials that cannot be dispensed using vacuum- or fluid
      filled systems. After inoculation, the sample was evaluated at a specified time
      interval for the presence of surviving bacteria, yeast, and mold. The lowest
      concentration of preservative with no microbial growth is the recommended level
      of preservative for the product. Because sample turbidity may interfere with
      determination of the endpoint, a colorimetric endpoint was used to indicate
      growth of microorganisms and to differentiate product from growth. The predicted
      levels were tested with a modified Cosmetic, Toiletry, and Fragrance Association
      method. The method successfully predicted effective preservative levels in many
      personal and home care products with a broad range of viscosities.

PMID- 9606918
TI  - In vitro study of nicotine release from smokeless tobacco.
AB  - Four brands (Copenhagen Snuff, Skoal Bandit Classic, Skoal Wintergreen Long Cut,
      and Skoal Wintergreen Fine Cut) of smokeless tobacco products were tested for
      their rate of nicotine release into artificial saliva via direct contact or
      through a dialysis bag. Nicotine was determined by reversed-phase liquid
      chromatography. When samples were in direct contact with artificial saliva, most
      of the nicotine was released from the tobacco in the first minute. Nicotine
      release from Skoal Bandit Classic, marketed as smokeless tobacco in a sachet, was
      slower with the sachet intact than without the sachet. When smokeless tobacco and
      artificial saliva were placed inside a dialysis bag, nicotine release was much
      slower and primarily depended upon the permeability of the dialysis membrane.
      Although total nicotine was lowest for Skoal Bandit Classic, little difference
      was seen in nicotine release rates among the brands tested. When smokeless
      tobacco was placed in dialysis bags with artificial saliva outside, a significant
      difference was seen in rates of nicotine migration through the membrane. In this
      model, nicotine release from Copenhagen Snuff was much faster than from Skoal
      Bandit Classic with or without the sachet. This difference may be related to the
      pH of the smokeless tobacco products.

PMID- 9606919
TI  - Occurrence of beta 2-adrenergic agonist residues in urine of animal meat
      producers in Portugal.
AB  - Between January 1, 1991, and December 31, 1993, bovine urine was collected for
      analysis of beta 2-adrenergic agonist residues. A multiresidue method was
      developed that was capable of detecting clenbuterol, clenpenterol, clenproperol,
      mabuterol, mapenterol, bromobuterol, tulobuterol, and salbutamol through enzyme
      linked immunosorbent assay, liquid chromatography (LC) with photodiode array
      detection, and gas chromatography with mass detection in electron impact mode
      with selective-ion monitoring. Among 1031 samples, 24 contained clenbuterol and 1
      contained salbutamol. The results confirm that clenbuterol is the beta 2
      adrenergic agonist most used as bovine growth promoter in Portugal.

PMID- 9606920
TI  - Determination of ivermectin in salmon muscle tissue by liquid chromatography with
      fluorescence detection.
AB  - A liquid chromatographic method was developed for determination of ivermectin B1a
      (IVR) extracted from raw fortified and incurred Atlantic salmon muscle tissues.
      The method was also used to determine fortified doramectin (DOR) in Atlantic
      salmon. Tissue extract was applied to C8 solid-phase extraction (SPE) column,
      followed by a silica SPE column. Residues in the eluate were treated with
      trifluoroacetic anhydride and methylimidazole to dehydrate the IVR molecule and
      form an aromatic fluorescent moiety with a trifluoroacetic ester. This product
      was subsequently treated with ammonium acetate in methanol to cleave the ester
      and convert the functional group back to a stable alcohol form. The analytes were
      determined by fluorescence with excitation at 272 nm and emission at 465 nm. A
      C18 Hypersil column was used for analysis with a mobile phase of acetonitrile
      water (90 + 10, v/v) and an oven temperature of 65 degrees C. IVR and DOR were
      determined at 5 fortification levels (1, 5, 10, 20, and 40 ppb). Intra-assay
      absolute recoveries ranged from 75 to 89% for IVR and from 73 to 85% for DOR.
      Relative standard deviations (RSDs) were < 7% in all cases. The limit of
      detection (3 x baseline noise) was 0.25 ppb extracted from tissue. Incurred
      tissues had an average concentration of 32 ppb, with an RSD of 3%.

PMID- 9606921
TI  - Confirmation of fluoroquinolones in catfish muscle by electrospray liquid
      chromatography/mass spectrometry.
AB  - A multiresidue liquid chromatography/mass spectrometry (LC/MS) confirmation
      method for fluoroquinolones in catfish muscle was developed by using an
      electrospray interface. Residues of ciprofloxacin, enrofloxacin, sarafloxacin,
      and difloxacin were positively identified in catfish muscle fortified at 10-80
      ppb as well as in incurred tissue. The extraction procedure is based on an LC
      method with fluorescence detection for determination of these compounds in
      catfish. Residues were extracted from catfish muscle with an acidic ethanol
      solution, and the extracts were cleaned up on a propyl sulfonic acid solid-phase
      extraction column. Chromatographic conditions were optimized to be compatible
      with the electrospray interface. Internal electrospray voltages were optimized so
      that 3 fragment ions, in addition to the protonated molecular ion, could be
      monitored for each residue. To obtain maximum sensitivity, separate MS
      acquisition programs were developed for ciprofloxacin/enrofloxacin and
      sarafloxacin/difloxacin pairs.

PMID- 9606922
TI  - Comparison of SimPlate Total Plate Count test with plate count agar method for
      detection and quantitation of bacteria in food.
AB  - The SimPlate Total Plate Count (TPC) test, developed by IDEXX Laboratories, Inc.,
      detects and quantitates total bacterial concentration in food after 24 h of
      incubation. The performance of SimPlate TPC was compared with that of the plate
      count agar (PCA) method for enumerating total bacterial concentration of 255 food
      samples representing 15 different food matrixes. Total bacterial counts on
      SimPlate TPC were measured after 24 h of incubation and plotted against values
      obtained from PCA after 48 h. Simple regression analysis of the data showed
      strong correlation between the methods (r = 0.95); the sensitivity of SimPlate
      TPC for foodborne bacteria was 96% relative to PCA (slope = 0.96). It was
      concluded that SimPlate TPC is a suitable alternative for the detection and
      quantitation of foodborne bacteria. The method has been granted Performance
      Tested Certification by the AOAC Research Institute.

PMID- 9606923
TI  - Liquid chromatographic method for analysis of All-rac-alpha-tocopheryl acetate
      and retinyl palmitate in soy-based infant formula using a zero-control reference
      material (ZRM) as a method development tool.
AB  - A liquid chromatographic method is described for analysis of all-rac-alpha
      tocopheryl acetate, tocopherols, and retinyl palmitate in soy-based infant
      formula. The vitamins are extracted in isopropyl alcohol and hexane--ethyl
      acetate without saponification and quantitated by normal-phase chromatography
      with fluorescence detection. All-rac-alpha-tocopheryl acetate and retinyl
      palmitate are quantitated isocratically with mobile phases of 0.5% (v/v) and
      0.125% (v/v) isopropyl alcohol in hexane, respectively. Recoveries from zero
      control reference material soy-based formula averaged 97.2% (n = 25) for retinyl
      palmitate and 100% (n = 25) for all-rac-alpha-tocopheryl acetate. Coefficients of
      variation ranged from 1.21 to 2.86% for retinyl palmitate and from 1.49 to 5.16%
      for all-rac-alpha-tocopheryl acetate. The method provides a rapid, specific, and
      easily controlled assay for analysis of vitamin A and vitamin E in fortified
      infant formula. Additionally, the method eliminates use of chlorinated solvents.

PMID- 9606924
TI  - Liquid chromatographic method for analysis of all-rac-alpha-tocopheryl acetate
      and retinyl palmitate in milk-based infant formula using matrix solid-phase
      dispersion.
AB  - A liquid chromatographic method is described for analysis of all-rac-alpha
      tocopheryl acetate, tocopherols, and retinyl palmitate in milk-based infant
      formula. The vitamins are extracted from infant formula without saponification by
      matrix solid-phase dispersion and quantitated by normal-phase chromatography with
      fluorescence detection. Retinyl palmitate and vitamin E are quantitated
      isocratically with mobile phases of 0.125% (v/v) and 0.5% (v/v) isopropyl alcohol
      in hexane, respectively. Results were similar to the certified and non-certified
      ranges for all-rac-alpha-tocopheryl acetate, retinyl palmitate, and tocopherols
      in the infant formula standard reference material (SRM) 1846. Results also
      compared favorably with the label declaration on a retail infant formula.
      Recoveries were determined on an analyte-fortified zero control reference
      material for milk-based infant formula and averaged 96.8% (n = 30) for retinyl
      palmitate and 91.5% (n = 25) for all-rac-alpha-tocopheryl acetate. Examination of
      5 concentrations for each analyte gave results that were linear (r = 0.999) over
      the concentration examined, with coefficients of variation ranging from 1.02 to
      5.86%. The method provides a rapid, specific, and easily controlled assay for
      analysis of retinyl palmitate and vitamin E in fortified infant formula.
      Additionally, the method minimizes solvent use by using only 14 mL solvent per
      extraction.

PMID- 9606925
TI  - Routine analysis of proteins by Kjeldahl and Dumas methods: review and
      interlaboratory study using dairy products.
AB  - The Kjeldahl and Dumas (combustion) methods were compared in 11 laboratories
      analyzing samples of milk, skim milk powder, whole milk powder, whey protein
      concentrate, infant formula, casein, caseinate, 2 reference compounds (glycine
      and EDTA), and a secondary reference skim milk powder. The comparison was
      conducted by using international standards where applicable. Overall means were
      8.818 g N/100 g by the Kjeldahl method and 8.810 g N/100 g by the Dumas method.
      No evidence was found for a consistent bias between methods that may be of
      concern in the trading of dairy produce. A review of more than 10 related trials
      revealed a lack of consensus in the bias between the 2 methods, suggesting that
      differences in methodology and sources of systematic error may be contributors.
      For samples containing > 2 g N/100 g, the Dumas relative repeatability and
      reproducibility standard deviations were consistently about 0.35 and 0.75%,
      respectively, whereas the corresponding Kjeldahl values declined generally with N
      content and were significantly larger. The Dumas precision characteristics may be
      due to the dominance of Leco analyzers in this trials, and in most other recent
      trials, rather than an inherent method attribute. Protein determination methods
      for dairy products need to be reviewed and updated. The Dumas method needs Codex
      Alimentarius status as a recognized test method.

PMID- 9606926
TI  - Merging zones standard addition technique for determination of copper in beer by
      flow injection atomic absorption spectrophotometry.
AB  - A flow injection system for determination of copper in beer by atomic absorption
      spectrophotometry by the standard additions method is described. The manifold,
      based on the merging zone technique, prevents the burner head from clogging, as
      observed with the conventional reference method. With 5 standard additions,
      results are comparable with those of the reference method. Relative deviations
      were less than 5.8%, precision was better than 6.4%, and sampling rate was about
      30 samples/ h. A less precise, less accurate, but faster procedure (75 samples/h)
      is possible with only 2 standard additions. The detection limit was 5
      micrograms/L.

PMID- 9606927
TI  - Release of fumigant residues from grain by microwave irradiation.
AB  - Multiresidue analysis of fumigants is important because of their widespread use
      on staple foodstuffs, such as grain. Fumigants are usually extracted from grain
      either by solvent extraction or by purge-and-trap techniques. In this paper,
      fumigant residues in wheat were "extracted" by a microwave procedure. Wheat, in
      gas-tight Erlenmeyer flasks, was placed in a domestic microwave oven, and
      fumigants were released into the headspace by microwave irradiation. Power
      settings for maximum release of fumigants were determined for CH3Br, PH3, CS2,
      and COS. Recoveries of fortified samples were > 90%. Completeness of extraction
      was assessed from the amount of fumigant retained by the microwave-irradiated
      wheat. This amount, determined from both solvent extraction and from further
      microwave irradiation, was always small (< 5% of the amount obtained from the
      initial procedure). Limits of quantitation were < 1 ng/g for CH3Br, PH3, and CS2.
      These low limits were essentially due to the absence of interference from
      solvents. The microwave method is rapid and solvent-free. However, care is
      required in selecting the appropriate power setting. The safety implications of
      heating sealed flasks in microwave ovens should be noted.

PMID- 9606928
TI  - Evidence for the use of assembled phonology in accessing the meaning of printed
      words.
AB  - The role of assembled phonology in visual word recognition was investigated using
      a task in which participants judged whether 2 words (e.g., PILLOW-BEAD) were
      semantically related. Of primary interest was whether it would be more difficult
      to respond "no" to "false homophones" (e.g., BEAD) of words (BED) that are
      semantically related to target words than to orthographic controls (BEND). (BEAD
      is a false homophone of BED because-EAD can be pronounced /epsilon d/.) In
      Experiment 1, there was an interference effect in the response time data, but not
      in the error data. These results were replicated in a 2nd experiment in which a
      parafoveal preview was provided for the 2nd word of the pair. A 3rd experiment
      ruled out explanations of the false homophone effect in terms of inconsistency in
      spelling-to-sound mappings or inadequate spelling knowledge. It is argued that
      assembled phonological representations activate meaning in visual word
      recognition.

PMID- 9606929
TI  - Depth-of-processing effects on priming in stem completion: tests of the voluntary
      contamination, conceptual-processing, and lexical-processing hypotheses.
AB  - Depth-of-processing effects on incidental perceptual memory tests could reflect
      (a) contamination by voluntary retrieval, (b) sensitivity of involuntary
      retrieval to prior conceptual processing, or (c) a deficit in lexical processing
      during graphemic study tasks that affects involuntary retrieval. The authors
      devised an extension of incidental test methodology--making conjunctive
      predictions about response times as well as response proportions--to discriminate
      among these alternatives. They used graphemic, phonemic, and semantic study
      tasks, and a word-stem completion test with incidental, intentional, and
      inclusion instructions. Semantic study processing was superior to phonemic study
      processing in the intentional and inclusion tests, but semantic and phonemic
      study processing produced equal priming in the incidental test, showing that
      priming was uncontaminated by voluntary retrieval--a conclusion reinforced by the
      response-time data--and that priming was insensitive to prior conceptual
      processing. The incidental test nevertheless showed a priming deficit following
      graphemic study processing, supporting the lexical-processing hypothesis. Adding
      a lexical decision to the 3 study tasks eliminated the priming deficit following
      graphemic study processing, but did not influence priming following phonemic and
      semantic processing. The results provide the first clear evidence that depth-of
      processing effects on perceptual priming can reflect lexical processes, rather
      than voluntary contamination or conceptual processes.

PMID- 9606930
TI  - Response distribution as an explanation of the mirror effect.
AB  - Response distribution has recently been proposed as an explanation of the mirror
      effect in recognition memory. According to the proposal, participants presented
      with distinctive sets of items (e.g., low- and high-frequency words) vary their
      responses to give an equal number of positive responses (e.g., the sum of hits
      and false alarms) to each set. Four experiments tested this proposal. Two
      experiments showed that the mirror effect is present in the absence of
      distinctive sets of items. Two experiments showed that the mirror effects is
      present in the absence of response equalization. Wherever the response
      distribution hypothesis can be tested, it fails.

PMID- 9606931
TI  - On the generality of the perceptual closure effect.
AB  - Perceptual closure is a process whereby an incomplete stimulus is perceived to be
      complete. J. G. Snodgrass and K. Feenan (1990) argued that perceptual closure
      during a study episode is an important factor in producing large priming effects
      in picture fragment identification. They found that a moderately fragmented study
      picture produced more priming than either a very fragmented or an intact study
      picture and argued that this inverted U-shaped function is a signature of the
      perceptual closure effect. The experiments in this study, extend these results to
      word fragment identification by showing that (a) the most effective prime, for
      both unspeeded and speeded word fragment identification is a moderately
      fragmented study word; (b) the sharpness of the U-shaped gradient is the same
      whether the perceptual feedback during study is a word (in a font different from
      that of the fragmented study word) or a picture; and (c) although a fragmented
      study picture primes subsequent word fragment identification, it does not produce
      the inverted U-shaped function, thereby showing that perceptual closure reflects
      perceptual rather than conceptual priming.

PMID- 9606932
TI  - Influences of prior knowledge on selective weighting of category members.
AB  - Three experiments addressed how prior theories affect categorization, comparing
      the influence of theory-congruent versus theory-incongruent category members.
      Subjects observed descriptions of persons, some congruent with prior knowledge
      and some incongruent, then made transfer judgments. In Experiment 1, subjects
      were given a relatively long time to study each description, whereas in
      Experiment 2 study time was manipulated between subjects. In Experiment 3,
      learning was self-paced by each subject. It was found that, with enough study
      time, prior knowledge had 2 distinct influences. First, prior knowledge provided
      an initial representation, subsequently revised in light of new observations.
      Second, incongruent observations had more impact than congruent observations on
      categorization. In comparison, when study time was more limited, revision
      proceeded in a Bayesian manner, in that congruent and incongruent observations
      had equal impacts.

PMID- 9606933
TI  - Categorical perception effects induced by category learning.
AB  - The authors report a series of studies designed to determine whether effects
      similar to those observed in the innate categorical perception of color and
      phonemes are induced during the learning of simple unidimensional categories and
      more complex multidimensional ones. In Experiment 1 no evidence was found for
      such effects when stimuli varied on 1 dimension. Experiments 2 and 3 demonstrated
      a within-category compression effect but no between category expansion effect for
      stimuli varying in 2 dimensions. Compression only was also shown in Experiment 4,
      which used pictures of actual objects. Multidimensional scaling analyses
      illustrate how within-category compression without expansion was sufficient to
      produce categorical clustering of items in the similarity space. These analyses
      also show that learning changed the dimensional structure of similarity space.
      Results are compared with those from other studies exploring similar phenomena
      and with neural network simulations.

PMID- 9606935
TI  - Antifungal nickel(II) complexes derived from amino sugars against pathogenic
      yeast, Candida albicans.
AB  - Nickel(II) complexes containing N-glycosides derived from D-glucosamine (D-GlcN)
      and ethylenediamine (en) and trimethylenediamine (tn), [Ni(D-GlcN-en)2]Cl2.H2O
      (1) (D-GlcN-en = 1-?(2-aminoethyl)amino?-2-amino-1,2-dideoxy-D-glucose) and [Ni(D
      GlcN-tn)2]Cl2.4H2O (2) (D-GlcN-tn = 1-?(3-aminopropyl)amino?-2-amino-1,2-dideoxy
      D-glucose), are fairly stable in water at room temperature and showed effective
      antifungal activity against pathogenic yeast, Candida albicans, with the MIC
      (minimal concentration of inhibition) values of the complexes being 0.25 mM. The
      results obtained enzyme assays by using preparations of C. albicans chitinase
      fraction suggested that the sugar complexes 1 and 2 played a role of novel
      chitinase (chitin-degradation enzyme) inhibitor, where the modes of inhibition
      were competitive (Ki = 1.3 mM for 1, Ki = 1.8 mM for 2). The newly prepared
      nickel(II) complex 2 was characterized by elemental analysis, magnetic
      susceptibility, electronic absorption and circular dichroism spectroscopies, and
      an X-ray crystallographic analysis.

PMID- 9606934
TI  - The reaction of lanthanide ions with n-doxyl stearic acids and its utilization
      for the ESR study on the permeability of lipid-bilayer of erythrocyte membrane to
      gadolinium ions.
AB  - The reaction of lanthanide ions with n-doxyl stearic acid (nDS) spin labels (n =
      5,7,12,16) was investigated by the electron spin resonance technique in aqueous
      solution. Among the lanthanides, the Gd3+, Tb3+, Tm3+ and Ce3+ ions strongly
      quenched the ESR signal of spin labels, but the effects of La3+, Eu3+ and Lu3+
      are very weak. The quenching effects are featured by: (1) the dependence on the
      concentration of lanthanide ions; (2) no obvious changes of the ESR line shape in
      the presence of lanthanide ions; (3) the quenching constant decreases in the
      order: Gd3+ > Tb3+ > Tm3+ > Ce3+; (4) the quenching effects of lanthanide ions
      are found to strikingly correlate with their magnetic properties. These findings
      indicate that the interaction of lanthanide ions with nitroxide oxygen leading to
      the reduction of ESR signal amplitude is dominated by their magnetic
      characteristics rather than the coordination effect. By labeling erythrocyte
      membrane with nDS, n = 5,7,12,16 at different depths, we studied the diffusion of
      Gd3+ into the lipid-bilayer of erythrocyte membrane by monitoring the reduction
      processes of the ESR signals of nitroxide spin labels located at different depths
      of membrane lipid-bilayer after addition of Gd3+. These results revealed that the
      Gd3+ ions can penetrate into the lipid-bilayer, though the entry rate is slow. It
      was shown that the Gd3+ ions bind to the membrane and enhance the permeability of
      extracellular ascorbate into erythrocyte membrane. The transport mechanism of
      Gd3+ ions through the lipid-bilayer might be involved in the Gd3+ cation-induced
      pore formation in the surface of membrane.

PMID- 9606936
TI  - Dimerization of tetracationic porphyrins: ionic strength dependence.
AB  - Cationic porphyrins are under study in a number of contexts including their
      interaction with biological targets, as possible therapeutic agents and as
      building blocks for molecular devices such as molecular photodiodes and solar
      cells. Many cationic porphyrins dimerize readily in aqueous solution.
      Dimerization in turn can control the properties of the porphyrin as well as its
      binding to its target. The propensity of a porphyrin to dimerize in aqueous
      solution can be estimated by recording the optical spectrum of the solution as a
      function of the concentration of added salt. Analysis of the data in terms of the
      Debye-Huckel formalism gives an estimate of the extent of dimerization as a
      function of ionic strength. Data for TMPyP4 [meso-tetrakis(4-N
      methylpyridinium)porphyrin] and its butyl and octyl homologs; TMAP [meso
      tetrakis(4-N,N,N-trimethylanilinium)porphyrin]; T theta PP [meso-tetrakis[4-N-[(3
      (trimethyl-ammonio)propyl)oxy]phenyl]porphyrin] and the ferrocenyl porphyrin P3Fc
      are discussed. Dimerization may affect binding of the cationic porphyrins to
      their targets, e.g., DNA.

PMID- 9606937
TI  - The coenzyme B12 derivative N1-methyl-5'-deoxyadenosylcobalamin: synthesis,
      characterization, stability towards dimroth rearrangement, and Co-C thermolysis
      product and kinetic studies.
AB  - The mechanism of Co-C heterolysis of adenosylcobalamin (AdoCbl) is studied,
      specifically the effect of a positive charge produced by methylation (CH3+, a
      "sticky proton" analog of H+ addition) to the most basic adenine N1 nitrogen site
      in AdoCbl. This is accomplished by the synthesis, characterization and Co-C
      thermolysis in the presence of the radical trap TEMPO of the N1 methylated AdoCbl
      derivative, [N1-methyl-5'-deoxyadenosycobalamin]+, 5. A variety of needed
      additional syntheses and other control experiments are also reported, including
      effective purification methods using ultrafiltration membranes, procedures that
      may prove to be the more generally useful part of the synthetic work reported.
      The thermolysis results with 5 are unequivocal in showing that a positive charge
      at the N1 nitrogen in the adenosyl group of AdoCbl has no effect within +/- 8% on
      the products or rates of Co-C thermal cleavage. The data are most consistent with
      a recently suggested, new mechanism for AdoCbl Co-C heterolysis at less acidic pH
      values, one not involving the protonation of the beta-ribose oxygen that is known
      to occur under strongly acidic conditions. In addition, the present study
      illustrates some of the positive features, and also some of the pitfalls, in the
      approach where CH3+ is used as a "sticky proton" analog in mechanistic studies.

PMID- 9606939
TI  - Binding of platinum-diaminonitroxyl complexes to animal DNA.
AB  - Reaction of PtII(DAPO)X2 complexes (where DAPO is trans-3,4-diamino-2,2,6,6
      tetramethylpiperidine-1-oxyl, X2 = (NO3)2, oxalato (Ox) or 1,1
      cyclobutanedicarboxylato (Cbdca)) with a bovine spleen DNA in 0.01 M NaHCO3 at 37
      degrees C for 24 h gives rise to formation of platinated DNA. The [bound
      PtII(DAPO)]/[nucleotide] ratio (r) depends on the initial ratio of the reagents
      and on the nature of leaving ligands X. Nitroxyl-nitroxyl distances in platinated
      DNA determined by the ESR suggest that at r > or = 0.1 PtII(DAPO) fragments are
      uniformly attached to DNA. But at lower r, the thermal characteristics of
      modified DNA (melting temperature Tm, melting range width delta T) and the
      guanine-to-adenine platination degree ratios GPt/APt imply that the nature of
      leaving ligands X affect the selectivity of DNA platination. At r > or = 0.1,
      nitroxyl groups can approach each other so close that, in an acidic medium, the
      electron transfer from one nitroxyl group to another becomes possible, and the
      nitroxyls readily disproportionate to diamagnetic products. Correlation time of
      nitroxyl rotation in PtII(DAPO)-DNA adducts is approximately 10(-8) s, which is
      related to predominantly bifunctional bonding of PtII(DAPO) with DNA. Platination
      induced distortion of DNA was evidenced by changes in Tm, delta T and degree of
      hyperchromicity H. The major part of adducts form the intrastrand cross-links
      which destabilize the structure of DNA duplex. The interstrand PtII(DAPO) cross
      linking (approximately 1% of the adducts) facilitates renaturation of
      despiralized DNA molecules upon cooling. Two types of PtII(DAPO)-DNA adducts are
      revealed, which differ substantially in their rates of deplatination with NaCN.
      ESR, electron spin resonance; r, degree of modification; cisplatin, cis
      diamminedichloroplatinum(II); Tm, melting temperature; delta T, melting range
      width; H, degree of hyperchromicity; R, degree of renaturation; AAS, atomic
      absorption spectroscopy; HPLC, high performance liquid chromatography.

PMID- 9606938
TI  - NMR studies of copper speciation in the bovine rumen environment.
AB  - Dietary copper supplements containing complexed copper have been asserted to be
      more bioavailable than 'inorganic' supplements. Since bioavailability is
      intimately related to the particular metal ion species that exist in any given
      environment, studies of solution speciation can be used to examine this
      assertion. In a previous study, our computer modeling of copper speciation in
      bovine saliva indicated that when a lysine-complexed copper supplement is used,
      the complex will not persist. In the present study, these conclusions are
      supplemented and extended using 1H NMR experiments. Lysine and the copper(II)
      lysine system are characterized, and chemical shifts of the individual species
      obtained. Chemical shift values for the copper(II)-lysine-bovine saliva system
      can then be predicted. Results show good agreement with experimental values. The
      scope of the computer modeling is then expanded to include the major low molar
      mass ligands present in the rumen. Implications of the results are discussed. The
      validity of this rumen model is further evaluated by NMR investigations on
      biological samples. The study provides further evidence that complexes such as
      copper(II)-lysine would disintegrate in the gastrointestinal tract, and are
      unlikely to be absorbed intact.

PMID- 9606940
TI  - Specific interactions of bovine and human beta-casomorphin-7 with Cu(II) ions.
AB  - Complex formation between Cu(II) and human and bovine beta-casomorphin
      heptapeptides, Tyr-Pro-Phe-Val-Glu-Pro-Ile and Tyr-Pro-Phe-Pro-Gly-Pro-Ile,
      respectively, was investigated by pH potentiometry and spectroscopic (CD, EPR and
      electronic absorption) techniques. The results showed the critical impact of Pro
      residues on the complex equilibria formed. The presence of the Pro residue at the
      second position leads to formation of very stable dimeric species in which two
      metal ions co-ordinate to N-terminal ?NH2, C=O? binding sites of one peptide
      molecule and the deprotonated phenolic oxygen of the second ligand molecule. The
      presence of two additional hydrophobic residues on the C-terminal makes
      heptapeptide molecule much more effective ligand than its pentapeptide N-terminal
      fragment.

PMID- 9606941
TI  - Organotin complexes with pyrrole-2,5-dicarboxaldehyde bis(acylhydrazones).
      Synthesis, structure, antimicrobial activity and genotoxicity.
AB  - Mono- and bimetallic organotin complexes with pyrrole-2,5-dicarboxaldehyde bis(2
      hydroxybenzoylhydrazone) (H5dfps) and pyrrole-2,5-dicarboxaldehyde bis(2
      picolinoylhydrazone) (H3dfpp) were synthesized and characterized by IR, 1H and
      119Sn NMR spectroscopy. X-ray analysis of the complex
      [Sn(H3dfps)(C6H5)2].(CH3)2SO revealed a pentacoordination around tin through a
      N,N,O terdentate ligand behaviour of the hydrazone. This complex is the most
      active compound, exhibiting MIC values of 3 and 12 micrograms/ml against Gram
      positive and Gram negative bacteria, respectively. None of the ligands or
      complexes produced DNA-damage in the Bacillus subtilis rec-assay or showed
      mutagenic activity in the Salmonella-microsome test.

PMID- 9606942
TI  - Cyanonitrosylmetallates as potential NO-donors.
AB  - The [M(CN)xNOy]n- complexes (where M = Cr(I), Mn(I), Mn(II), Fe(I), Fe(II),
      Fe(III)) were studied as potential NO-donors using both pharmacological and
      theoretical semi-empirical methods. Only iron complexes appeared to be
      pharmacologically active. The quantum chemical calculations indicated that these
      complexes have the highest predisposition to undergo a nucleophilic attack
      followed by the NO+ release. The results allowed us to interpret the metabolism
      of the [M(CN)xNOy]n- complexes in terms of the NO(+)-donation.

PMID- 9606943
TI  - Hemocytes of the palaemonids Macrobrachium rosenbergii and M. acanthurus, and of
      the penaeid Penaeus paulensis.
AB  - The hemocytes of two palaemonids and one penaeid were characterized using light
      and transmission electron microscopy (TEM). The blood cells in all three species
      were classified as hyaline hemocytes (HH), small granule hemocytes (SGH), and
      large granule hemocytes (LGH). The HH are unstable hemocytes with a
      characteristic high nucleo-cytoplasmic ratio. Their cytoplasm appears
      particularly dense and has from few to numerous granules that often exhibit a
      typical striated substructure. In both palaemonids, the great majority of the HH
      contain numerous granules, whereas in Penaeus paulensis, a small number of these
      cells have few or no granules. The cytoplasm of some HH of the penaeid exhibits
      typical electron-dense deposits. The granulocytes, LGH and SGH, contain abundant
      electron-dense granules that are usually smaller in the SGH. In both hemocyte
      types, the cytosol, but not the granules, is rich in carbohydrates (PAS positive)
      and numerous vesicles contain acid phosphatase (Gomori reactive). In all studied
      shrimps, the SGH and LGH were actively phagocytic when examined on blood cell
      monolayers incubated with the yeast Saccharomyces cerevisiae. A few mitotic
      figures (less than 1%) were observed in the granulocytes of P. paulensis, but not
      in the palaemonids. SGH is the main circulating blood cell type in both
      palaemonids, whereas HH is predominant in the penaeid. Based on morphological and
      functional features, it appears that the hyaline and the granular hemocytes of
      the three shrimp species represent different cell lineages.

PMID- 9606944
TI  - Indoor and outdoor measurements of vertical concentration profiles of airborne
      particulate matter.
AB  - Vertical concentration profiles of various particle size ranges of airborne
      particulate matter were measured from ground level up to 3 m, in outdoor and
      indoor environments. Indoor measurements were carried out in an electronics
      workshop, while two outdoor environments were chosen: a street canyon cutting
      across a town and an open field situated in a semi-rural environment. The novel
      measurement technique employed in this experimental work, which can also be used
      to determine vertical concentration gradients of pollutants other than airborne
      particles in different environments, is given particular attention. Analyses of
      the collected data for the environments considered are presented and some
      conclusions and plausible explanations of the profiles are discussed. The
      workshop and street canyon environments exhibited larger concentrations and
      vertical concentration gradients as compared to the sports field. This indicates
      that people breathing at different heights are subjected to different
      concentrations of airborne particulate matter, which has implications for sitting
      air pollution monitors intended for protection of public health and estimation of
      human exposure.

PMID- 9606945
TI  - Personal exposure to nitrogen dioxide in Switzerland. SAPALDIA team. Swiss Study
      on Air Pollution and Lung Diseases in Adults.
AB  - Home indoor and outdoor levels, and personal exposures to NO2 were determined for
      more than 500 subjects in a subpopulation of SAPALDIA by using passive samplers.
      The overall personal NO2 average was found to be 27 micrograms m-3, the overall
      indoor average 21 micrograms m-3 and the overall outdoor average 31 micrograms m
      3. Personal NO2 levels ranged between the outdoor and indoor levels, with the
      exception of study areas with low NO2 concentrations. In the winter, the
      indoor/outdoor ratios were lower than in the summer. Outdoor NO2 levels were
      higher in winter. In some study areas, indoor NO2 levels were lower in the winter
      than in the summer due to reduced ventilation but this was not consistent.
      Personal NO2 concentrations were very similar during all seasons. Gas-cooking and
      smoking were important factors for elevated indoor and personal NO2 levels
      (contribution: 5 micrograms m-3, 2 micrograms m-3, respectively). Personal
      exposure to NO2 correlated best with the indoor NO2 concentrations.

PMID- 9606946
TI  - Impact of the New Zealand flatworm (Artioposthia triangulata) on soil structure
      and hydrology in the UK.
AB  - Through north west Europe, concern has been growing in recent years about the
      predatory nature of Artioposthia triangulata on indigenous earthworm species. In
      this study, the consequence of earthworm depletion by A. triangulata on soil
      structure and related hydrological processes is examined. Field measurements
      compare differences in saturated hydraulic conductivity between sites overrun by
      A. triangulata and neighbouring unaffected sites. Laboratory experiments were
      conducted on soil cores containing worms only, worms and A. triangulata, and a
      control with no worms or A. Triangulata. Differences in the water release
      characteristic and bulk density between treatments was studied. It is concluded
      that in the short term, infestation by flatworms and consequent depletion of
      earthworms will increase infiltration. However, as macropores degenerate or are
      removed over time, an increased risk of surface run off may result in increased
      pollution and flood hazards, whilst reduced drainage and subsequent waterlogging
      may reduce agricultural productivity in certain soils. More research into
      understanding the processes is required.

PMID- 9606947
TI  - Expectancy effects in memory for melodies.
AB  - Two experiments explored the relation between melodic expectancy and melodic
      memory. In Experiment 1, listeners rated the degree to which different endings
      confirmed their expectations for a set of melodies. After providing these
      expectancy ratings, listeners received a recognition memory test in which they
      discriminated previously heard melodies from new melodies. Recognition memory in
      this task positively correlated with perceived expectancy, and was related to the
      estimated tonal coherence of these melodies. Experiment 2 extended these results,
      demonstrating better recognition memory for high expectancy melodies, relative to
      medium and low expectancy melodies. This experiment also observed asymmetrical
      memory confusions as a function of perceived expectancy. These findings fit with
      a model of musical memory in which schematically central events are better
      remembered than schematically peripheral events.

PMID- 9606948
TI  - Multidimensional scaling of synthetic musical timbre: perception of spectral and
      temporal characteristics.
AB  - The perceptual correlates of acoustic parameters involved in musical timbre were
      investigated by examining judgements of timbre dissimilarity. Nine synthetic
      sounds were created, derived from crossing three levels of spectral and temporal
      parameters (number of harmonics and rise time, respectively). Two separate
      conditions were tested, one using single tones, the other using short melodies.
      Fifteen musically untrained subjects were presented with pairs of stimuli and
      asked to judge dissimilarity on an 8-point scale. The spatial configuration
      resulting from multidimensional analysis of the data was best fit by a three
      dimensional model, with the first two dimensions accounting for most of the
      variance. The perceptual space derived from the analysis indicates that these two
      orthogonal dimensions corresponded closely to the spectral and temporal
      differences inherent to the stimuli. Similar results were obtained with both
      melodies and single tones. A second experiment replicated the findings despite
      the introduction of random loudness variation, indicating that timbre judgements
      can be made independently of loudness. We conclude that even musically unselected
      subjects are sensitive to spectral and temporal information in musical tones, and
      are able to use them independently in making perceptual judgements of musical
      timbre.

PMID- 9606949
TI  - An exploratory study of musical emotions and psychophysiology.
AB  - A basic issue about musical emotions concerns whether music elicits emotional
      responses in listeners (the 'emotivist' position) or simply expresses emotions
      that listeners recognize in the music (the 'cognitivist' position). To address
      this, psychophysiological measures were recorded while listners heard two
      excerpts chosen to represent each of three emotions: sad, fear, and happy. The
      measures covered a fairly wide spectrum of cardiac, vascular, electrodermal, and
      respiratory functions. Other subjects indicated dynamic changes in emotions they
      experienced while listening to the music on one of four scales: sad, fear, happy,
      and tension. Both physiological and emotion judgements were made on a second-by
      second basis. The physiological measures all showed a significant effect of music
      compared to the pre-music interval. A number of analyses, including correlations
      between physiology and emotion judgments, found significant differences among the
      excerpts. The sad excerpts produced the largest changes in heart rate, blood
      pressure, skin conductance and temperature. The fear excerpts produced the
      largest changes in blood transit time and amplitude. The happy excerpts produced
      the largest changes in the measures of respiration. These emotion-specific
      physiological changes only partially replicated those found for nonmusical
      emotions. The physiological effects of music observed generally support the
      emotivist view of musical emotions.

PMID- 9606950
TI  - Monitoring and planning capacities in the acquisition of music performance
      skills.
AB  - We investigate changes in cognitive capacities that occur as musicians acquire
      performance skills. Previous studies suggest that skilled behaviour is
      characterized by advanced abilities to monitor one's own performance or to plan
      upcoming events. We first report a study of child pianists (aged 6-14 years old)
      of beginning and intermediate skill levels who performed well-learned musical
      pieces. Computer-detected pitch errors in the performances provided evidence for
      skill-related increases in both monitoring and planning: Children with more
      musical training showed quicker detection and correction of errors, more
      anticipatory and less perseveratory behavior, and larger range of planning than
      children with less training. Next we report a study of adult musicians' advanced
      performances, which showed heightened sensitivity to melody and repeated pitch
      structures. Planning and monitoring capacities increased most during initial
      stages of musical skill acquisition, whereas sensitivity to musical structure
      increased across all skill levels.

PMID- 9606951
TI  - Parents' sung performances for infants.
AB  - Naive listeners rated the style of singing in mothers' and fathers' sung
      performances for infants and their simulations of those performances (Experiment
      1). Performances in an infant's presence were judged as more expressive--either
      more playful or more soothing--than were simulations. Parents' style of singing,
      as reflected in these ratings, differed as a function of the sex of singer and
      listener. Both parents sang more playfully for same-sex infants than for opposite
      sex infants. Independent listeners rated the manner in which parents enunciated
      the lyrics of their songs (Experiment 2). Parents rendered the lyrics of songs
      more expressively in infant-present than in infant-absent contexts. Moreover,
      this expressiveness was greater for same-sex infants than for opposite-sex
      infants. These findings are consistent with parents' greater attachment to same
      sex infants. Discrepancies between parents' choice of songs and their manner of
      singing lend credence to functional rather than nominal classifications of songs
      for infants.

PMID- 9606952
TI  - Phosphorylation of farnesol in rat liver microsomes: properties of farnesol
      kinase and farnesyl phosphate kinase.
AB  - As farnesol may serve as a nonsterol endogenous regulator of the mevalonate
      pathway, the possibility that a kinase specific for its phosphorylation is
      present in the rat liver was investigated. In the 10,000 g supernatant of rat
      liver, farnesyl monophosphate was synthesized in the presence of ATP. The Km
      value for farnesol was 2.3 microM. Various detergents inhibited the activity of
      the enzyme. The farnesol kinase was present in rough and in smooth I microsomes,
      but not in smooth II microsomes, mitochondria, peroxisomes, Golgi, or plasma
      membranes. The enzyme was associated with the inner, luminal surface of the
      vesicles. Further analyses have demonstrated that an enzymatic mechanism exists
      which catalyzes the phosphorylation of farnesyl-P to farnesyl-PP. Activity of the
      farnesyl phosphate kinase resulted in the phosphorylation of the monophosphate by
      CTP but not by ATP, GTP, or UTP. This enzyme is activated by low concentrations
      of detergents. Treatment with proteases and chemical probes indicate that this
      second phosphorylation reaction probably takes place on the outer, cytoplasmic
      surface of microsomal vesicles. These results demonstrate that rat liver
      microsomes contain two enzymes for the consecutive phosphorylation of farnesol to
      farnesyl-PP.

PMID- 9606953
TI  - Loss of K+ homeostasis in trout hepatocytes during chemical anoxia: a screening
      study for potential causes and mechanisms.
AB  - In isolated trout hepatocytes intoxication with CN- (chemical anoxia) leads to a
      rapid breakdown of K+ homeostasis. In the present study an attempt has been made
      to identify the causes and mechanisms underlying this phenomenon. Our results
      indicate that neither Ca2+ elevation nor cell swelling, both of which occurred
      during chemical anoxia and could be prevented by exposure to Ca2+ chelating
      agents or to hyperosmotic conditions, respectively, is solely responsible for the
      breakdown of K+ homeostasis. From a number of inhibitors of dissipative K+ fluxes
      tested, only BaCl2, an inhibitor of voltage-gated K+ channels, proved to be
      effective in significantly reducing K+ efflux during chemical anoxia. The KCl
      cotransporter known to be involved in regulatory volume decrease after
      hypoosmotic shock does not seem to be activated during CN(-)-induced cell
      swelling.

PMID- 9606954
TI  - Laccase--and not tyrosinase--is the enzyme responsible for quinone methide
      production from 2,6-dimethoxy-4-allyl phenol.
AB  - Tyrosinase, which is known to possess both monophenol monooxygenase activity (EC
      1.14.18.1, tyrosine, 3,4-dihydroxyphenylalanine:oxygen oxidoreductase) and o
      diphenoloxidase activity (EC 1.10.3.1, o-diphenol:oxygen oxidoreductase), has
      been shown to exhibit other related activities. Recently, a new reaction, viz.,
      oxidative conversion of 2,6-dimethoxyallyl phenol to its quinone methide,
      catalyzed by commercial preparations of mushroom tyrosinase was reported (E. S.
      Krol, and J. L. Bolton, 1997, Chem. Biol. Interact. 104, 11-27). Since the
      reaction involves an unusual 1,6-oxidation rather than the conventional 1,4
      oxidation, we reexamined this reaction more carefully. The o-diphenoloxidase
      activity and the dimethoxyallyl phenol oxidase activity of mushroom tyrosinase
      preparations exhibited different mobilities on size-exclusion chromatography on a
      Sephacryl S-200 column. A similar behavior was also witnessed on preparative
      isoelectric focusing in a rotofor cell. Different preparations of mushroom
      tyrosinase possessed varying ratios of these two activities, further confirming
      that they are due to two different enzymes. Native polyacrylamide gel
      electrophoresis followed by activity staining of the gel revealed different
      mobilities for these two activities. The protein band exhibiting dimethoxyallyl
      phenol oxidase activity could also be stained by syringaldazine, a well-known
      substrate for laccase (EC 1.10.3.2, p-diphenol:oxygen oxidoreductase). Two insect
      phenoloxidases, which are known for their wide substrate specificity, failed to
      oxidize dimethoxyallyl phenol to any detectable extent, thereby confirming that
      typical o-diphenoloxidases lack the ability to oxidize dimethoxyallyl phenol. On
      the other hand, laccase, which is known to convert syringaldazine to its quinone
      methide derivative, readily produced the quinone methide from dimethoxyallyl
      phenol. It is therefore concluded that laccase, which is present as a contaminant
      in the commercial preparations of mushroom tyrosinase--and not tyrosinase (o
      diphenoloxidase)--is the enzyme responsible for catalyzing the new conversion of
      dimethoxyallyl phenol to its corresponding quinone methide.

PMID- 9606955
TI  - Characterization of a silencer element in the human aromatase gene.
AB  - Aromatase, a cytochrome P450, catalyzes three consecutive hydroxylation reactions
      converting C19 androgens to aromatic C18 estrogens. The control of human
      aromatase expression is complex in that several promoters drive aromatase
      expression in a tissue-specific manner. Promoters I.3 and II are situated within
      the 700-bp region immediately upstream of exon II of the human aromatase gene,
      and these promoters have been shown to drive aromatase expression in breast
      tumors. This paper reports the characterization of a negative regulatory element
      that is situated between promoters I.3 and II and down regulates the action of
      these promoters. This negative regulatory element is thought to be a silencer
      element (S1) because it acts in an orientation- and promoter-independent manner.
      The position of S1 (5'-CCAAGGTCAGAAATGCTGCAATTCAAGCCA-3') was mapped by DNase I
      footprinting and DNA deletion analyses. The region contains three pairs of
      inverted repeats, as indicated by an underline, probably explaining why S1
      functions in both orientations. Chloramphenicol acetyltransferase functional
      analyses indicated that the transcriptional activity of promoter I.3 was
      suppressed two- to three-fold by S1. Mutations of two inverted repeat segments
      (i.e., TTC and CC) in S1 destroyed its silencing action and modified the protein
      binding patterns in DNA mobility shift analysis. UV cross-linking experiments
      with 32P-labeled bromodeoxyuridine-substituted S1 as the probe and nuclear
      extracts from MCF-7 breast cancer cells and skin fibroblasts revealed that four
      major nuclear proteins, with molecular masses of approximately 150, 45, 30, and
      25 kDa, bound to this element. Interestingly, two smaller proteins could be
      competed by an unlabeled fragment which contains promoter I.3. In addition,
      mutation of S1 at the region CC destroyed the ability to compete with the wild
      type S1 for the binding of 30- and 25-kDa proteins. These results led us to
      propose that S1 down regulates the action of promoter I.3, and the 30- and 25-kDa
      proteins present in the nuclear extract of MCF-7 cells and skin fibroblasts are
      involved in the silencer action.

PMID- 9606956
TI  - Analysis of the gene encoding cyclomaltodextrinase from alkalophilic Bacillus sp.
      I-5 and characterization of enzymatic properties.
AB  - The gene encoding cyclomaltodextrinase (CDase) was cloned from alkalophilic
      Bacillus sp. I-5. The nucleotide sequence of the gene was determined and the
      physicochemical properties of the enzyme were investigated. The gene had an open
      reading frame of 559 amino acids with a predicted molecular weight of 64,884. The
      enzyme was purified to near homogeneity from Escherichia coli cells carrying a
      recombinant plasmid that contained the CDase gene. The enzyme hydrolyzed
      cyclomaltoheptaose (beta-CD) 13 times better than starch and 33 times better than
      pullulan, and it had transglycosylation activity. The enzyme also hydrolyzed
      acarbose, a pseudotetrasaccharide inhibitor of glucosidases. The enzyme was
      stabilized by Ca2+ and the activity was increased more than twofold in the
      presence of 5 mM EDTA. The optimum temperature of the enzyme was elevated from 40
      to 50 degrees C by Ca2+ ion and the thermal activity was maintained more than 80%
      at 60 degrees C in the presence of Ca2+. Comparison of known amino acid sequences
      of several amylolytic enzymes with cyclomaltodextrinase activity, site-directed
      mutagenesis of the enzyme, and substrate specificity of the enzyme imply that the
      region between the third and the fourth conserved regions of the enzyme may play
      an important role in binding and degradation of cyclomaltodextrin.

PMID- 9606957
TI  - Interactions of substrate and product with cytochrome P450: P4502B4 versus
      P450cam.
AB  - In the present study, two P450s (P4502B4 and P450cam) have been examined with
      regard to their interactions with their substrates and products utilizing the
      characteristic spectral perturbations as criteria for their binding. The results
      indicate that although there are differences between the two P450s (E) in regard
      to their precise interactions with their substrates (S) and products (P), the
      spectral titration data were consistent with the two-site model--E + S<-->ES
      (K1), E + P<-->EP (K2); EP + S<-->ESP (K3); ES + P<-->ESP (K4) in which S and P
      bind to E forming ESP. The data were inconsistent with the two-site model in
      which S and P compete for the same site. As required by the two-site model, the
      relationship K2K3 = K1K4 was maintained with both P450s at all product
      concentrations tested, although K3 and K4 decreased considerably when product
      concentration was increased. The relationship K3 >> K4 was also maintained,
      indicating that with both enzymes' ESP is formed predominantly by binding of S to
      EP rather than binding of P to ES, and that ESP dissociates predominantly to ES
      and P rather than EP and S. In other words, binding of S to EP facilitates the
      dissociation of P. This indicates that the relative parameter values are
      compatible for ESP to have functional significance. The possible role of ESP in
      controlling catalytic rate and catalytic efficiency is discussed.

PMID- 9606958
TI  - Convulxin induces platelet activation by a tyrosine-kinase-dependent pathway and
      stimulates tyrosine phosphorylation of platelet proteins, including PLC gamma 2,
      independently of integrin alpha IIb beta 3.
AB  - 1Convulxin (Cvx) is a well-characterized platelet aggregating glycoprotein
      isolated from Crotalus durissus terrificus and C. d. cascavella venoms. In the
      present report we show that Cvx induces tyrosine phosphorylation of human
      platelet proteins, including phospholipase C-gamma 2 (PLC gamma 2), and also
      stimulates [3H]arachidonic acid ([3H]AA) mobilization, pleckstrin
      phosphorylation, and an increase in the cytosolic Ca2+ concentration ([Ca2+]in)
      due to both Ca2+ entry and internal Ca2+ mobilization. Staurosporine, a potent
      protein kinase inhibitor, and genistein, a specific inhibitor of protein tyrosine
      kinases (PTK), were used to evaluate the role of protein tyrosine phosphorylation
      (PTP) in the signal transduction evoked by Cvx. Staurosporine and genistein
      inhibited in a dose-dependent manner platelet aggregation induced by Cvx. Both
      inhibitors significantly blocked to near basal levels breakdown of
      phosphatidylinositol 4,5-bisphosphate from [myo-2-3H]inositol-labeled platelets
      and the production of [3H]AA metabolites from [3H]AA-labeled platelets after
      challenge with Cvx. Cvx provokes an increase in [Ca2+]in in Fura-2-loaded
      platelets that was abolished by concentrations of staurosporine which also
      inhibited Cvx-induced platelet aggregation. In addition, Cvx stimulates a rapid
      increase in tyrosine phosphorylation of human platelets proteins with molecular
      masses of 40, 72/74, 78/80, 105, 120, and 145 kDa, followed by dephosphorylation.
      Furthermore, Cvx stimulates a rapid tyrosyl phosphorylation of a 145-kDa
      molecular mass protein that was identified as PLC gamma 2. PTP induced by Cvx was
      not inhibited when platelets were stimulated in the presence of indomethacin,
      apyrase, EDTA, or RGDS peptide. These results indicate that PTP is
      chronologically proximal to Cvx binding to platelets, and is independent of
      aggregation or fibrinogen binding to the integrin alpha IIb beta 3. On the other
      hand, the dephosphorylation step is inhibited by RGDS peptide or EDTA, suggesting
      that integrin alpha IIb beta 3 is envolved in this step. The profile obtained
      with Cvx resembles that obtained in platelets adherent to an immobilized ligand,
      such as immobilized collagen, in which PTP is independent on integrin alpha IIb
      beta 3. Thus, we suggest that Cvx is an example of a protein with adhesion
      molecule-like properties; i.e., it is an adhesin. In conclusion, our results show
      that Cvx induces multiple signaling pathways in platelets via a PTK-dependent
      pathway involving PLC gamma 2 tyrosyl phosphorylation, with the subsequent
      platelet responses. Cvx is unique among platelet soluble agonists because under
      test tube stirring conditions it induces a PTP profile independently of integrin
      alpha IIb beta 3.

PMID- 9606959
TI  - In vivo phosphorylation of phosphofructokinase from the bivalve mollusk Mytilus
      galloprovincialis.
AB  - The phosphorylation state of phosphofructokinase from the mantle tissue of the
      facultative anaerobe mollusk Mytilus galloprovincialis was determined by a back
      phosphorylation technique. The incubation of intact mantle tissue with 8
      bromoadenosine 3':5'-cyclic monophosphate increased significantly the phosphate
      content of phosphofructokinase, which indicates that the enzyme can be
      phosphorylated in vivo by endogenous cAMP-dependent protein kinase. The phosphate
      content of mussel phosphofructokinase changes significantly during the year, in
      agreement with the kinetic data that show a more active enzyme form in earlier
      autumn. These results suggest that cAMP-dependent phosphorylation of
      phosphofructokinase can be partially responsible for the observed glycolytic
      changes associated with the annual gametogenic cycle that takes place in the
      mantle tissue of the mollusk. On the contrary, no differences were observed
      between aerobic and 24-h hypoxic mussels with regard to the phosphorylation state
      and the kinetic constants of phosphofructokinase. This result is inconsistent
      with the hypothesis that phosphorylation of phosphofructokinase is involved in
      the glycolytic depression that takes place during the long-term environmental
      hypoxia that the mollusk can undergo.

PMID- 9606960
TI  - Characterization of the cytochrome P450 CYP2J4: expression in rat small intestine
      and role in retinoic acid biotransformation from retinal.
AB  - The sites of expression in the small intestine and the function of CYP2J4, a
      recently identified rat cytochrome (P450) isoform found to be predominantly
      expressed in the small intestine, were characterized. Immunoblot analysis with a
      polyclonal antibody to heterologously expressed CYP2J4 revealed that expression
      of CYP2J4 was at the highest level in the distal duodenum and jejunum and
      decreased toward the ileum. Villous cells expressed higher levels of CYP2J4 than
      crypt cells. Isoform-specific RNA polymerase chain reaction indicated that a
      related P450 isoform, CYP2J3, was only a minor form in rat small intestine. Since
      the intestinal mucosa is exposed to high levels of dietary nutrients, we
      hypothesized that CYP2J4 may be active toward diet-derived factors. We determined
      that purified, heterologously expressed CYP2J4 is active toward all-trans- and 9
      cis-retinal in reconstituted systems, producing the corresponding retinoic acids
      as the major products. Apparent K(m) values for the formation of retinoic acids
      were 54 and 49 microM, respectively, and apparent Vmax values were 20 and 21
      nmol/min/nmol P450, respectively. These activities were readily inhibited by a
      polyclonal anti-CYP2J4 antibody. Rat enterocyte microsomes were also active with
      all-trans-retinal to produce all-trans-retinoic acid in the presence of NADPH,
      and the majority of retinoic acid synthesis activity was inhibited by the
      polyclonal anti-CYP2J4 antibody. These findings suggest that CYP2J4 plays a major
      role in intestinal microsomal metabolism of retinal to retinoic acid and may be
      involved in the maintenance of retinoid homeostasis in the small intestine in
      vivo.

PMID- 9606961
TI  - Arachidonic acid metabolism in the marine fish Stenotomus chrysops (Scup) and the
      effects of cytochrome P450 1A inducers.
AB  - Cytochrome P450-mediated arachidonic acid (AA) metabolism was investigated in the
      marine fish scup, Stenotomus chrysops. Liver microsomes incubated with AA and
      NADPH produced epoxyeicosatrienoic acids (EETs) and their hydration products
      (dihydroxyeicosatrienoic acids, DHETs), midchain conjugated dienols (midchain
      HETEs), and C16-through C20-alcohols of AA (omega-terminal HETEs), all identified
      by HPLC and GC/MS. Gravid females had 4-fold lower AA metabolism rates than males
      but identical metabolite profiles. The 5,6-EET (inferred from stable metabolites)
      was most abundant (47% of total EETs) followed by 14,15-, 11,12-, and 8,9-EET
      (27, 13, and 13%, respectively). The 12-HETE represented 25% of total HETEs
      followed in abundance by 16-, 15-, 11-, 19-, 20-, 8-, and 9-HETE. Antibodies
      against scup CYP1A and a scup CYP2B-like protein inhibited liver microsomal AA
      metabolism by 30 and 46%, respectively. GC/MS analysis revealed EETs and DHETs as
      endogenous constituents in scup liver; the predominant EETs were 8,9- and 14,15
      EET, followed by a lesser amount of 11,12-EET. Chiral analysis showed a
      preference for the S,R-enantiomers of endogenous 8,9-, 11,12-, and 14,15-EET
      (optical purities 80, 64, and 64%, respectively). Treatment of scup with the
      CYP1A inducer benzo(a)pyrene (BP) increased liver microsomal formation of EETs
      and HETEs by 2.7-fold in spring and 1.7-fold in summer. BP treatment did not
      affect microsomal EET regioselectivity, but shifted hydroxylation in favor of 19
      HETE and induced 17-HETE formation. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)
      treatment in summer did not induce liver microsomal AA metabolism rates, yet BP
      and TCDD both increased endogenous EET content of liver (5- and 3-fold,
      respectively), with a shift to 14,15-EET. BP treatment increased the selectivity
      for the S,R-enantiomers of endogenous 8,9-, 11,12-, and 14,15-EET (optical
      purities 91, 84, and 83%, respectively). Kidney, gill, and heart microsomes all
      metabolized AA, at rates 10- to 30-fold less than liver microsomes. Similar
      amounts of endogenous 8,9- and 14,15-EET and less 11,12-EET were detected in
      heart and kidney, and there was a strong enantioselectivity for 8(R),9(S)-EET in
      heart (optical purity 78%) but not in kidney. BP treatment did not alter the
      total EET content in these organs but did shift the regiochemical profile in
      heart to favor 14,15-EET. Thus, scup liver and extrahepatic organs metabolize AA
      via multiple cytochrome P450 (CYP) forms to eicosanoids in vitro and in vivo. BP
      or TCDD induced endogenous AA metabolism in liver, altering EET regioselectivity
      and, with BP, stereoselectivity. While AhR agonists alter metabolism of AA in
      early diverging vertebrates expressing both CYP1A and AhR, the magnitude of
      effects may depend upon the type of inducer.

PMID- 9606962
TI  - Identification of a mitochondrial RNA polymerase in the crustacean Artemia
      franciscana.
AB  - Mitochondrial RNA polymerase activity has been isolated from the crustacean
      Artemia franciscana at two stages of development, dormant embryo and developing
      larva. The preparations were obtained from purified mitochondria and the
      polymerase activity was purified by heparin-Sepharose chromatography. The
      presumed polymerase has a molecular mass of about 120 kDa and a 7.4 S
      sedimentation coefficient. The biochemical characterization of the enzymatic
      reaction identified our RNA polymerase preparations as mitochondrial. The
      transcription initiation sites of Artemia mtDNA were characterized recently in
      our laboratory (J. A. Carrodeguas and C. G. Vallejo, Eur. J. Biochem. 250, 514
      523, 1997). Artemia mtDNA fragments comprising the transcription initiation sites
      were transcribed by the partially purified polymerase preparation from the two
      developmental stages, but the transcription turned out to be unspecific. DNAse I
      footprinting analysis of a main transcription initiation site-containing DNA
      fragment revealed a protected region around the initiation site +1 position, when
      using a crude polymerase preparation. However, the protected region was not
      observed with the purified preparation. The results altogether suggest that a
      specificity factor is lost during purification. Based on the footprinting data,
      we suggest that the sequence from positions -6 to +13 of the main transcription
      initiation site in the Artemia mitochondrial DNA is the binding site of the
      homologous RNA polymerase holoenzyme.

PMID- 9606963
TI  - Cytochrome P450cam substrate specificity: relationship between structure and
      catalytic oxidation of alkylbenzenes.
AB  - The oxidation by cytochrome P450cam (CYP101) of ethylbenzene and a series of
      substrates derived from it by addition of one, two, three, or four carbon atoms
      has been examined. For each of the 18 substrates, the shift in spin state due to
      substrate binding, the extent of coupled turnover to give organic products and
      uncoupled turnover to give H2O2 and H2O, and the identities of the organic
      products have been determined. The same studies have been carried out with the
      T185L and T185F mutants of P450cam in which the active site volume is decreased.
      The results show that no detectable correlation exists between the observed spin
      state change and any other parameter studied. For substrates of equal size,
      coupled and uncoupled turnover vary widely but both are maximized when the phenyl
      ring bears one large alkyl substituent or a methyl ortho to the largest alkyl
      substituent. The presence of substituents in addition to these decreases
      activity. In the absence of other changes, coupled turnover is correlated with
      the size of the largest substituent, but no such correlation exists for uncoupled
      turnover. Decreasing the size of the active site cavity by a T185L mutation
      generally increases coupled turnover without altering the dependence on the alkyl
      group size. A T185F mutation causes too great an active site perturbation for
      structure-activity studies. Substrate oxidation occurs preferentially at 2
      degrees or 3 degrees C-H bonds of the largest substituent or on the benzylic
      methyl ortho to it. Aromatic hydroxylation only competes with the oxidation of
      nonbenzylic 1 degree C-H bonds. The extent of coupled turnover is a function of
      substrate shape, substrate size, and cavity size, but still elusive parameters
      control the extent of uncoupled turnover.

PMID- 9606964
TI  - Overexpression, purification, and stereochemical studies of the recombinant (S)
      adenosyl-L-methionine: delta 24(25)- to delta 24(28)-sterol methyl transferase
      enzyme from Saccharomyces cerevisiae.
AB  - The ERG6 gene that encodes (S)-adenosyl-L-methionine: delta 24(25)-to delta
      24(28)-sterol methyl transferase (SMT) enzyme from Saccharomyces cerevisiae was
      introduced into plasmid pET23a(+) and the resulting native protein was
      overexpressed in BL21 (DE3) host cells under control of a T7 promoter. This
      enzyme was purified to apparent homogeneity by ammonium sulfate precipitation,
      anion exchange, and hydrophobic interaction chromatography. N-Terminal sequence
      analysis of the first 10 amino acids of the purified SMT protein confirmed the
      identity of the start triplet and expected primary structure. The enzyme
      exhibited a turnover number of 0.01/s and an isoelectric point of 5.95. A
      combination of Superose 6 chromatography and sodium dodecyl sulfate
      polyacrylamide gel electrophoresis showed that the purified SMT enzyme possessed
      a native molecular weight of 172,000 and was tetrameric. The purified SMT enzyme
      generated kinetics in which velocity versus substrate curves relative to
      zymosterol (preferred sterol acceptor molecule) and AdoMet were sigmoidal rather
      than hyperbolic, indicating enzyme cooperativity among the subunits. Studies on
      product formation using [27-13C]zymosterol and [2H3-methyl]AdoMet incubated with
      the pure SMT enzyme confirmed the reaction mechanism of sterol methylation to
      involve a 1,2-hydride shift of H-24 to C-25 from the Re-face of the original
      24,25- double bond. Deduced amino acid sequence comparisons of the SMT
      polypeptide from S. cerevisiae with related sterol methyl transferase enzymes of
      plant and fungal origin indicate that there is a significant degree of similarity
      between these enzymes. Specifically, there is a conserved sequence (in yeast from
      amino acids ca. 79 to 92 which contains an YEXGWG motif; referred to as Region I)
      that is not present in other AdoMet-dependent methyl transferase enzymes.

PMID- 9606965
TI  - Measurement and characterization of superoxide generation in microglial cells:
      evidence for an NADPH oxidase-dependent pathway.
AB  - While oxygen free radicals are important mediators of brain injury, questions
      remain regarding which cell types and enzyme pathways trigger this radical
      generation. Microglial cells have been hypothesized to be an important source of
      radical generation; however, the magnitude, kinetics, and mechanism of this
      process are unknown. Oxygen radical generation by stimulated primary microglia
      was directly measured and characterized by electron paramagnetic resonance spin
      trapping. Microglia, when stimulated by phorbol ester or opsonified zymosan, gave
      rise to EPR spectra characteristic of superoxide. Experiments performed in the
      presence of superoxide dismutase, catalase, deferoxamine, and dimethyl sulfoxide
      excluded generation of hydroxyl radicals in significant amounts. Microglial
      superoxide generation was blocked by the NADPH oxidase inhibitor diphenylene
      iodonium in a manner similar to that seen in neutrophils, suggesting that a
      neutrophil like NADPH oxidase was the source of superoxide production. However,
      microglia produced 20 to 40 times less superoxide compared to a similar number of
      neutrophils during the first 30 min following stimulation, indicating a marked
      difference in the regulation of NADPH oxidase activation. Western blots of
      microglia lysates demonstrated that both large (gp91-phox) and small (p22-phox)
      NADPH oxidase subunits are expressed in both unstimulated and stimulated
      microglia. Indirect immunofluorescence demonstrated localization at the membrane
      surfaces of activated cells. Thus, microglial cells generate superoxide via a
      neutrophil-like NADPH oxidase but exhibit distinctly different time course and
      magnitude of activation than that seen in neutrophils.

PMID- 9606966
TI  - An atypical cytochrome b in the colorless alga Polytomella spp.: the high
      potential bH heme exhibits a double transition in the alpha-peak of its
      absorption spectrum.
AB  - Polytomella spp. is a colorless alga of the family Chlamydomonadaceae that lacks
      chloroplasts and cell wall. A highly active ubiquinol-cytochrome c oxidoreductase
      (bc1 complex), sensitive to antimycin and myxothiazol, has been purified and
      characterized from this alga (Gutierrez-Cirlos et al., 1994, J. Biol. Chem. 269,
      9147-9154). Both in mitochondrial membranes and in the isolated complex, the
      visible spectrum of cytochrome b from Polytomella spp. exhibits an atypical alpha
      band with a maximum at 567 nm. This maximum is shifted 3-4 nm to the red when
      compared with b-type cytochromes from other organisms. Analysis of the b hemes of
      the bc1 complex by high performance liquid chromatography revealed no differences
      in the retention time and in the absorption spectra of the b-type hemes from
      Polytomella spp. and hemin, indicating that the prosthetic group in this alga is
      protoheme and thus ruling out the possibility that the red-shift could be due to
      different chemical substitutions in the porphyrin rings of the bL or bH hemes.
      The two b hemes were characterized by electrochemical redox titration; at pH 7.8
      8.0, the midpoint potential for bL was-143 mV and for bH +25 mV. The spectra of
      the two b-type hemes were recorded in the presence of different reductants, at
      selected electrochemical potentials, and in the presence of antimycin A, to
      distinguish between the contribution of bL and bH to the visible spectrum. Both
      hemes bL and bH of the algal cytochrome b contribute to the observed bathochromic
      absorption maximum in the alpha-band of the spectrum. The data also show that the
      low potential bL heme from Polytomella spp. is spectroscopically similar to that
      of other organisms, with two transitions in the alpha-peak at 558.7 and 568.4 nm.
      The high-potential heme bH also exhibits a spectrum with two transitions at 557.2
      and 568.9 nm, which surprisingly differs from the spectra of cytochrome bH of
      mammals, plants, yeasts, and bacteria, which all exhibit a single transition
      centered around 560 nm.

PMID- 9606967
TI  - Cloning and characterization of the CYP2D1-binding protein, retinol
      dehydrogenase.
AB  - A CYP2D1-binding protein, 29 k-protein (p29), has been isolated and its N
      terminal amino acid sequence has been reported (Ohishi et al. (1993) Biochim.
      Biophys. Acta 1158, 227-236). In this study, p29 cDNA was isolated by PCR with
      oligonucleotide probes designed from the N-terminal amino acid sequence and p29
      was found to be a microsomal retinol dehydrogenase, a member of the short-chain
      alcohol dehydrogenase family which metabolize hydroxysteroids and prostaglandins.
      CYP2D1 and p29 were expressed in Saccharomyces cerevisiae to characterize these
      proteins. CYP2D1 had an absorption maximum at 448 nm in a CO-reduced form.
      Expressed p29 in yeast cells was detected with anti-p29 antibody. Solubilized
      CYP2D1 and p29 from yeast microsomes were mixed and applied to an anti-CYP2D1
      antibody-binding column. Both proteins were retained in the column and eluted
      with glycine buffer (pH 2.8). However, when applied alone, p29 was not retained
      in the column. The findings indicated that CYP2D1 bound tightly with p29.
      Catalytic activities of p29 expressed in yeast were investigated. p29 had retinal
      reductase activity in the presence of NADPH. Addition of CYP2D1 and NADPH-P450
      reductase increased the retinal reductase activity of p29. These findings suggest
      that the complex of CYP2D1, p29, and NADPH-P450 reductase has an important role
      in the metabolism of retinoids.

PMID- 9606968
TI  - Cloning, expression, and biochemical characterization of a functionally novel
      alpha class glutathione S-transferase with exceptional activity in the
      glutathione conjugation of (+)-anti-7,8-dihydroxy-9,10-oxy-7,8,9,10
      tetrahydrobenzo(a)pyrene.
AB  - The present study describes cDNA cloning, expression, and kinetic
      characterization of the two subunits of a murine alpha-class glutathione (GSH) S
      transferase (GST) isoenzyme (previously designated as GST 9.5), which, unlike
      other alpha-class mammalian GSTs, is exceptionally efficient in the GSH
      conjugation of (+)-anti-7,8-dihydroxy-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene
      [(+)-anti-BPDE] [X. Hu, S. K. Srivastava, H. Xia, Y. C. Awasthi, and S. V. Singh
      (1996) J. Biol. Chem. 271, 32684-32688]. The cDNAs for both subunits of GST 9.5
      (GST 9.5-1 and GST 9.5-2) were cloned by RT-PCR. The deduced amino acid sequences
      of GST 9.5-1 and GST 9.5-2 clones were identical to those of mGSTA1 and mGSTA2,
      respectively. Both these subunits were expressed in Escherichia coli to determine
      the relationships between recombinant mGSTA1-1 and mGSTA2-2 and corresponding
      subunits of tissue-isolated GST 9.5. The pI values of recombinant mGSTA1-1 and
      mGSTA2-2 (9.49 and 9.45, respectively) were similar to that of the tissue
      isolated isoenzyme (pI 9.5). The reverse-phase HPLC elution profiles and
      immunological cross-reactivities of recombinant mGSTA1-1 and mGSTA2-2 were also
      similar to those of the corresponding subunits of tissue-isolated GST 9.5. The
      catalytic efficiency of recombinant mGSTA1-1 toward (+)-anti-BPDE, 131 mM-1.s-1,
      was approximately 9.5-to 655-fold higher compared with tissue-isolated mGSTP1-1,
      mGSTA3-3, mGSTM1-1, and mGSTA4-4. Moreover, the catalytic efficiency of mGSTA1-1
      toward (+)-anti-BPDE was about 3.3-fold higher compared with recombinant mGSTA2
      2. The mGSTA1 and/or mGSTA2 subunits were expressed to varying degrees in female
      A/J mouse tissues. For example, mGSTA1, but not mGSTA2, subunit expression was
      observed in the skin, which is a target organ for benzo(a)pyrene (BP)-induced
      cancer in mice. On the other hand, the expression of either mGSTA1 or mGSTA2
      subunit could not be detected in the lung, which is another target organ for BP
      induced cancer in mice. Interestingly, relatively large amounts of both mGSTA1
      and mGSTA2 subunits were detected in the kidney. In conclusion, the results of
      the present study clearly indicate that the A1-type subunit of GST 9.5 is
      responsible for its exceptional catalytic efficiency in the GSH conjugation of
      (+)-anti-BPDE, which is the ultimate carcinogen of widespread environmental
      pollutant BP.

PMID- 9606969
TI  - Purification and characterization of laccases from the white-rot basidiomycete
      Dichomitus squalens.
AB  - Two chromatographic forms of laccase c1 and c2 were purified approximately 225
      fold from the extracellular culture fluid of ligninolytic cultures of Dichomitus
      squalens, using DEAE-Sepharose and Mono-Q fast protein liquid chromatography.
      Each homogeneous laccase (c1 and c2) has a molecular mass of approximately 66 kDa
      as determined by SDS-PAGE. Both forms are glycoproteins, and each contains four
      copper atoms per molecule of protein. The first 20 amino acids of the N-terminal
      sequences of these two laccases are identical and are similar to those of
      laccases from other lignin-degrading fungi. The electronic absorption spectra of
      these laccases exhibit bands at 610 and 330 nm, indicative of type I and type III
      copper. The EPR spectrum of laccase c1 exhibits bands indicative of type I and
      type II copper. Each laccase oxidizes a variety of phenolic substrates, has a pH
      optimum of 3.0 for the oxidation of 2,6-dimethoxyphenol, and is inhibited
      strongly by fluoride and azide.

PMID- 9606970
TI  - Structural selectivity and molecular nature of L-glutamate transport in cultured
      human fibroblasts.
AB  - Uptake of L-[3H]glutamate by monolayers of fibroblasts cultured from human
      embryonic skin has been studied in the presence of several nonradioactive
      structural analogs of glutamate and aspartate. Results have suggested that the
      structural specificites of glutamate transporters in cultured human fibroblasts
      are similar to those of glutamate transporters in the mammalian brain. Only
      subtle differences have been detected: in the mammalian cerebral cortex,
      enantiomers of threo-3-hydroxyaspartate are almost equipotent as inhibitors of L
      [3H]glutamate uptake while, in human fibroblasts, the D-isomer has been found to
      be an order of magnitude less potent than the corresponding L-isomer. Kinetic
      analysis of a model in which substrates are recognized by the glutamate
      transporter binding site(s) as both alpha- and beta-amino acids indicated that
      such a mechanism cannot explain the apparent negative cooperativity
      characterizing the effects of D- and L-aspartate. Molecular modeling has been
      used to estimate the optimum conformation of L-glutamate as it interacts with the
      transporter(s). Flow cytometry has indicated that all fibroblasts in culture
      express at least moderate levels of four glutamate transporters cloned from human
      brain. Small subpopulations (< 3%) of cells, however, were strongly labeled with
      antibodies against EAAT1 (GLAST) and EAAT2 (GLT-1) transporters. We conclude that
      these two transporters--known to be strongly expressed in brain tissue--can be
      principally responsible for the "high affinity" transport of glutamate also in
      nonneural cells.

PMID- 9606971
TI  - Oxidation of nonionic detergents by cytochrome P450 enzymes.
AB  - Nonionic phenolic detergents are commonly used in the purification of membrane
      associated proteins. Triton N-101 was shown to be oxidized by NADPH-fortified
      human liver microsomes and recombinant human cytochromes P450 (P450). Oxidation
      was monitored using HPLC and the fluorescence properties of Triton N-101 and
      other alkylphenol ethoxylate detergents, which are similar to those of anisole.
      Human liver microsomes and recombinantly expressed reconstituted P450 3A4
      oxidized Triton N-101 in a concentration-dependent manner which could be
      inhibited by ketoconazole, a P450 3A4-selective inhibitor. Triton N-101
      inhibition of testosterone oxidation by human liver microsomes was of a mixed
      nature but mainly non-competitive. Electrospray ionization mass spectrometry and
      tandem mass spectrometry indicated that the major product formed was hydroxylated
      on the alkyl moiety. Human liver microsomes also oxidized other Tritons (X-100
      and X-114), Emulgens 911 and 913, and Tergitol NP-10 to a similar extent. P450s
      1A1, 1A2, and 2C9 also oxidized Triton N-101 but to a lesser extent than P450
      3A4. We conclude that Triton N-101 and similar nonionic detergents are oxidized
      by P450 3A4 and some other P450s.

PMID- 9606972
TI  - Inhibitors of calcineurin block expression of cyclins A and E induced by
      fibroblast growth factor in Swiss 3T3 fibroblasts.
AB  - In Swiss 3T3 fibroblasts, growth factor-stimulated progression from G1 to S phase
      involves activation of the Ca2+/calmodulin-dependent serine/threonine-specific
      protein phosphatase 2B (calcineurin). Here we report that both cobalt and the
      calcium chelator EGTA, inhibitors of calcium uptake, as well as cyclosporin A and
      FK-506, specific inhibitors of calcineurin function, abolished fibroblast growth
      factor (FGF)-induced expression of cyclins A and E, but not cyclin D1. At 0.1
      microM concentration cyclosporin A completely blocked FGF-induced expression of
      cyclins E and A and it inhibited FGF-stimulated DNA synthesis by 40%; full
      inhibition of DNA synthesis required 10 microM cyclosporin A. PD 98059, an
      inhibitor of mitogen-activated protein (MAP) kinase kinase, and hemicholinium-3,
      an inhibitor of FGF-induced MAP kinase activity, did not inhibit the stimulatory
      effect of FGF on the expression of cyclin E. On the other hand, the inhibitory
      effect of 0.1 microM cyclosporin A on FGF-stimulated DNA synthesis was additive
      with that of hemicholinium-3, suggesting that the two inhibitors acted by
      different mechanisms. The inhibitors of calcineurin and calcium uptake also
      completely blocked the stimulatory effects of lysophosphatidic acid on the
      expression of cyclins E and A, but not cyclin D1. The results suggest that FGF-
      or lysophosphatidic acid-induced transcription of cyclin A and cyclin E genes is
      mediated by calcineurin involving a MAP kinase-independent mechanism and that
      increased expression of cyclins A and E is required for the maximal stimulatory
      effects of these mitogens on DNA synthesis.

PMID- 9606973
TI  - Ets transcription factors and human disease.

PMID- 9606974
TI  - DAP genes: novel apoptotic genes isolated by a functional approach to gene
      cloning.

PMID- 9606975
TI  - Nucleocytoplasmic transport and cell proliferation.

PMID- 9606977
TI  - MDM2 function.

PMID- 9606976
TI  - The Elongin BC complex and the von Hippel-Lindau tumor suppressor protein.

PMID- 9606978
TI  - The role of protein stability in the cell cycle and cancer.
AB  - In addition to the examples mentioned above, other important regulators of cell
      proliferation such as cyclin D, cyclin E, p21, p27 are all potentially controlled
      by ubiquitin-mediated proteolysis. In several of these, phosphorylation has been
      shown to play a role in targeting the proteins for degradation. It remains to be
      seen how important the SCF pathway and ubiquitin-mediated proteolysis, in
      general, will become in cancer research. However, it appears that we have only
      just scratched the surface on the role of these pathways in the control of
      important regulatory genes. We suspect there will be much more to come from
      analysis of these fascinating pathways.

PMID- 9606980
TI  - Actin polymerization and bacterial movement.

PMID- 9606979
TI  - Matters of life and death: programmed cell death at Cold Spring Harbor.

PMID- 9606981
TI  - The small intestinal fructose transporters: site of dietary perception and
      evidence for diurnal and fructose sensitive control elements.
AB  - To obtain an insight into the mechanisms responsible for GLUT5 diurnality and
      fructose responsiveness, rats were gavaged at 9:00 AM or 6:00 PM with 1 g of
      fructose in the presence or absence of cycloheximide. After 4 h of fructose
      exposure, GLUT5 mRNA and protein levels increased 2-3.5-fold above the natural
      diurnal levels of expression. In situ hybridization and immunochemical analysis
      of GLUT5 mRNA and protein demonstrated that both diurnality and fructose
      responsiveness was confined to mature enterocytes. The protein synthesis
      inhibitor, cycloheximide, blunted the diurnal and fructose driven increase in
      GLUT5 mRNA expression in the morning, but had minimal effect on the pattern of
      expression in the evening. This differential sensitivity of intestinal GLUT5 mRNA
      to de novo protein synthesis may reflect the increasing presence of diurnal and
      fructose sensitive control factors during the day. Following vehicle gavage,
      Cycloheximide was more effective in reducing GLUT5 protein expression levels in
      the morning when compared to the evening. These data suggest that the turnover of
      GLUT5 protein may be diurnally influenced.

PMID- 9606982
TI  - Measuring transferrin receptor gene expression by NMR imaging.
AB  - The human transferrin receptor (hTfR) has been used as a model molecular target
      to direct therapeutic agents to tumor cells and to shuttle drugs across the blood
      brain-barrier. We show in the current study that receptor expression and
      regulation can be visualized by NMR imaging, when the receptor is probed with a
      sterically protected iron containing magnetic hTfR probe. We were able to
      demonstrate that the novel receptor probe was an iron source that could enter the
      cells via the hTfR but did not play an immediate role in iron downregulation of
      hTfR within incubation times tested. Using genetically engineered rat 9L
      gliosarcoma cell lines with three different forms of the hTfR, we also
      demonstrated that receptor expression and regulation can be visualized by NMR
      imaging using the probe. This research provides proof of the principle that it is
      possible to image receptor gene expression and regulation and it demonstrates
      that it may be possible to image gene transfer in vivo.

PMID- 9606983
TI  - A chemically modified tetracycline inhibits streptozotocin-induced diabetic
      depression of skin collagen synthesis and steady-state type I procollagen mRNA.
AB  - Wasting of connective tissues including skin, bone, and cartilage have been
      closely associated with elevated matrix metalloproteinase (MMP) activity and
      depressed collagen content in the streptozotocin (STZ)-induced diabetic rat,
      while tetracyclines have been reported to normalize total body weight, skin
      hydroxyproline and collagen content in this model, in part through inhibition of
      MMPs. In the present study, we report the effect of CMT-1, a chemically modified
      tetracycline that lacks antimicrobial properties but retains divalent cation
      binding and MMP inhibitory activity, on diabetic skin collagen synthesis and
      steady-state levels of procollagen alpha 1(I) mRNA. Male, 4-month old Sprague
      Dawley rats received a single injection of 75 mg/kg STZ or citrate vehicle alone
      and diabetic status was confirmed by positive glucosuria. Some diabetic animals
      received 10 mg/day of CMT-1 by oral gavage and, 28 days after STZ treatment, body
      weight, blood glucose values and the in vivo rates of skin collagen production
      were measured using the pool-expansion technique. Steady-state levels of
      procollagen alpha 1(I) mRNA were analyzed 21 days after STZ treatment by
      hybridization of total RNA with a 32P labelled cDNA to rat type I procollagen
      alpha 1(I) mRNA in a dot-blot assay. STZ treatment was found to significantly
      depress body weight, skin collagen hydroxyproline content, the in vivo rate of
      collagen production, and hybridizable levels of type I procollagen alpha 1(I)
      mRNA. CMT-1 administered daily to STZ-treated rats inhibited the diabetic
      depression of these parameters but had little or no effect on non-diabetic
      controls or on STZ-induced hyperglycemia. Thus, in addition to the inhibition of
      MMP mediated extracellular collagen degradation, these results suggest CMT-1 also
      acts to inhibit diabetic connective tissue breakdown in STZ-induced diabetes by
      increasing both steady-state levels of type I procollagen mRNA and collagen
      synthesis through mechanism(s) that are independent of the antibacterial
      properties of tetracyclines.

PMID- 9606984
TI  - Characterization of glycerol uptake and glycerol kinase activity in rat
      hepatocytes cultured under different hormonal conditions.
AB  - Glycerol uptake and glycerol kinase activity were studied in primary cultures of
      rat hepatocytes in the presence of either 1 nM insulin, 1 nM glucagon, or 100 nM
      dexamethasone, alone or in combination in the culture medium. Glycerol uptake
      exhibited saturation kinetic with K(m) values (microM) and Vmax (nmol/min x mg
      protein) ranging from 250-402, and 7.9-10.1, respectively. The corresponding K(m)
      and Vmax values for glycerol kinase activity were 36-46 and 8.7-12.7. Using the
      metabolic uncoupler 2,4-dinitrophenol, glycerol uptake and the cellular content
      of glycerol phosphorylated metabolites were reduced 33% and 43%, respectively,
      whereas no decrease in the cellular content of glycerol was seen. The glycerol
      analogues monoacetin, monobutyrin and dihydroxypropyl dichloroacetate were able
      in a concentration-dependent manner to inhibit glycerol uptake into hepatocytes
      with the two latter having IC50 values of approximately 1 mM. Moreover, it was
      demonstrated that the three glycerol analogues were substrates for glycerol
      kinase, which indicates a competitive mode of inhibition. The kinetic parameters
      for these substrates were calculated by using glycerol kinase from Candida
      Mycoderma. Monobutyrin was found to be 4 times lees efficient as substrate
      compared to the other substrates. Overall, these results indicate that
      independently of the culture conditions, glycerol uptake is the rate-limiting
      step in glycerol metabolism, and that the investigated glycerol analogues are
      metabolized via the same route as glycerol.

PMID- 9606985
TI  - Expression of LFA-1 adhesion molecules on cisplatin-treated macrophages.
AB  - Appropriately activated mononuclear phagocytes mediate contact-dependent
      tumoricidal activity. Adhesion structures involved in contact-dependent tumor
      cytotoxicity have not been defined. The present study was aimed at identifying
      the adhesion structure involved in the tumoricidal activity of cisplatin
      activated murine peritoneal macrophages. Tumor cells of different histological
      origin were used as targets in a 24-h cytotoxicity assay. Anti-CD18 (LFA-1 beta)
      substantially inhibited macrophage cytotoxicity whereas anti-LFA-1 alpha
      marginally inhibited macrophage-mediated cytotoxicity. When combined together,
      almost complete inhibition of tumoricidal activity was observed. Activated
      macrophages showed augmented binding to target cells and anti-LFA MAb inhibited
      the binding of resting and activated macrophages to target cells. Cisplatin
      augmented the expression of LFA-1 alpha and beta integrins and LPS had no effect
      as assessed by immunoprecipitation. These results implicate that in cisplatin
      activated macrophages LFA-1 alpha and beta integrins are important molecules in
      contact-dependent tumoricidal activity.

PMID- 9606986
TI  - Effects of human lactoferrin on NK cell cytotoxicity against haematopoietic and
      epithelial tumour cells.
AB  - Lactoferrin is an iron-binding glycoprotein implicated in particular in the
      control of immune functions and cell proliferation. We have investigated its
      involvement, at inflammatory concentrations, in cancer progression. We report
      that lactoferrin has a significant effect on natural killer (NK) cell
      cytotoxicity against haematopoietic and breast epithelial cell lines. Lactoferrin
      increases cytolysis at a low concentration (10 micrograms/ml) while at a high
      concentration (100 micrograms/ml) it modulates cytolysis depending on the target
      cell phenotype. By pre-treatment of either NK cells or target cells with
      lactoferrin, we have demonstrated that the lactoferrin effect is due both to a
      modulation of NK cell cytotoxicity and the target cell sensitivity to lysis.
      Lactoferrin binds to 91% of the naturally heterogeneous CD56dim/bright NK cell
      population and increases the NK cell cytotoxic activity at low concentrations.
      High concentrations of lactoferrin seem to be toxic for the CD56bright NK cells
      and decrease NK cell cytotoxicity. Lactoferrin also exerts an effect on target
      cells depending on the cell phenotype. It does not modify the susceptibility to
      lysis of haematopoietic cells such as Jurkat and K-562 cells, but does
      significantly increase that of the breast and colon epithelial cells. We have
      also demonstrated that lactoferrin inhibits epithelial cell proliferation by
      blocking the cell cycle progression.

PMID- 9606987
TI  - Cloning and tissue distribution of the human G protein beta 5 cDNA.
AB  - Heterotrimeric G proteins integrate signals between receptors and effector
      proteins. We have cloned the human beta 5 subunit from a human brain cDNA
      library. The clone has a 1059 bp open reading frame and is highly homologous to
      the murine clone. In contrast to the brain specific mouse beta 5, northern
      analysis showed it to be expressed in multiple tissues.

PMID- 9606989
TI  - Cyclic AMP-dependent protein kinase (PKA) gene expression is developmentally
      regulated in fetal lung.
AB  - We characterized the ontogeny of cAMP-dependent protein kinase (PKA) enzymatic
      activity and PKA subunit mRNA expression in developing lung. The lungs of fetal
      Sprague-Dawley rat pups were removed after 16, 18, or 20 days of gestation and at
      term. PKA activity was greatest in the 18- and 20-day gestation lungs. Tissue
      cAMP levels were lowest in the 16-day lungs and increased with lung maturity. We
      were able to detect only low levels of mRNA for the C beta subunit of PKA by
      northern blot analysis of total lung RNA and we were able to detect mRNA for the
      RI beta and RII beta subunits only by RT-PCR. Therefore, we limited our analysis
      of PKA subunit mRNA levels to those for C alpha, RI alpha and RII alpha. The mRNA
      levels for C alpha, were highest in the 16-day lung, decreased at 18 and 20 days,
      were lower in the newborn and lowest in the adult lung. RI alpha mRNA levels were
      also highest at 16 days and lowest in the adult lung. However, RII alpha mRNA
      levels were similar in the 18-day, 20-day and newborn lungs. Dexamethasone
      treatment of fetal lung explants resulted in a small decrease in RI alpha mRNA
      levels but was not associated with a change in PKA activity. We conclude that PKA
      activity and PKA subunit mRNA expression are developmentally regulated in fetal
      lung. Such regulation results in optimal PKA activity at the time of type II
      alveolar cell differentiation, presumably in preparation for air breathing. The
      absence of an effect of glucocorticoid on PKA activity suggests that
      glucocorticoids are not responsible for the increase in PKA activity which
      accompanies this critical time in lung maturation.

PMID- 9606988
TI  - Specific detection of phosphatidylinositol 3,4,5-trisphosphate binding proteins
      by the PIP3 analogue beads: an application for rapid purification of the PIP3
      binding proteins.
AB  - Phosphatidylinositol (PI) 3-kinase is known as one of the key molecules involved
      in the various biological events such as vesicle trafficking, cytoskeletal
      rearrangements and cell survival. T clarify the molecular basis underlying these
      events, we have tried to identify the proteins that can interact with
      phosphatidylinositol 3,4,5-trisphosphate (PIP3), the lipid product of PI3-kinase.
      Using a new PIP3 analogue, PIP3-APB, we synthesized an affinity column for PIP3
      binding proteins. This enabled us to purify and identify several PIP3 binding
      proteins such as Tec tyrosine kinase, Gap1m, and Akt, as the candidates for the
      downstream molecules of PI3-kinase. All of these proteins contain PH domains,
      possible binding sites for phospholipids. Studies with various deletion mutants
      of Tec or Gap1m revealed that their PH domains are indeed the binding sites for
      PIP3. These results demonstrate that this PIP3-analogue binds various PIP3
      binding proteins with high specificity and may be useful to elucidate the
      downstream mechanisms of PI3-kinases-mediated signaling pathways.

PMID- 9606990
TI  - Modulation of the activation status of Stat5a during LIF-induced differentiation
      of M1 myeloid leukemia cells.
AB  - Treatment of M1 myeloid leukemia cells with leukemia inhibitory factor (LIF)
      causes activation of transcription factors Stat1, Stat3 and Stat5a (signal
      transducers and activators of transcription). DNA-binding of Stat proteins was
      detectable for extended periods of time in LIF-treated M1 cells, which
      simultaneously underwent terminal differentiation. The relative composition of
      Stat factors in the protein-DNA complexes changed during time. Whereas Stat3 was
      activated up to 36 h during treatment with LIF, Stat5a was activated only short
      termed. Similarly, high expression of the immediate early gene CIS (cytokine
      inducible SH2-containing protein), a known target gene of Stat5 in hematopoietic
      cells, occurred only during the onset of differentiation. This suggests a role of
      Stat5a in the early phase of LIF-induced differentiation and growth arrest of M1
      cells.

PMID- 9606991
TI  - Evidence for preferential T cell receptor V beta gene usage and T cell clonal
      expansion in the synovium of BB rats with early-onset collagen-induced arthritis.
AB  - Type II collagen (CII) is a potent arthritogen in the BB rat. To determine
      whether a restricted group of T cells is involved in the pathogenesis of collagen
      induced arthritis, lymphocytes from synovium, peripheral blood, and lymph nodes
      of arthritic rats were studied for T cell receptor (TCR) V beta gene usage using
      polymerase chain reaction (PCR). Oligoclonal TCR V beta usage was found only in
      synovium recovered day 2 post-arthritis onset, but not day 7; lymph node and
      peripheral blood T cells showed diverse TCR usage at both times. To determine
      whether T cell local clonal expansion occurred in synovium at day 2 of arthritis,
      cDNA for four TCR beta families was sequenced through VDJ regions. Strong
      selective expansion of TCR V beta 8.2, 4, and 17 was noted. Importantly, the
      dominant clonotype of V beta 8.2 was identical to that of a lymph node-derived T
      hybridoma specific for the immunodominant epitope in CII(181-210). Cells from
      synovium (day 2 postonset) analyzed by flow cytometry also showed V beta 8.2+
      cell enrichment. These observations, plus finding that T cells from inflamed
      synovium respond to CII(181-201) in vitro, suggest the local recruitment and
      clonal expansion of some T cells families, possibly driven by autologous CII
      released during cartilage degradation.

PMID- 9606992
TI  - Gangliosides enhance apoptosis of thymocytes.
AB  - Monosialogangliosides, normal components of cell membranes, regulate cell
      development and differentiation in several organs. Our previous observation of
      dramatic premature thymic involution in cats with feline GM1 gangliosidosis,
      whose thymocytes have abnormally high cell surface gangliosides, suggested that
      excess GM1 ganglioside (GM1) could modulate thymocyte apoptosis in this disease
      (Cox et al., "Thymic Alterations in Feline GM1 Gangliosidosis," submitted). In
      these studies, we added exogenous GM1 to murine primary thymocyte cultures and
      demonstrated enhanced apoptosis in treated cells by DNA fragmentation, apoptotic
      body, and electrophoretic analyses. GM1-enhanced apoptosis was blocked by common
      apoptotic pathway inhibitors including aurintricarboxylic acid (inhibitor of
      endonuclease activity), actinomycin D (inhibitor of RNA transcription), and
      cycloheximide (inhibitor of protein synthesis). GM1 treatment primarily affected
      the immature CD4+ CD8+ subset, as shown by flow cytometric evaluation of fetal
      thymic organ culture and primary thymocyte cultures. Apoptosis also could be
      induced by GM2, GM3, and GT1b, whereas asialo-GM1 failed to do so, suggesting
      that the sialic acid moiety may play an important role in the induction of
      thymocyte apoptosis.

PMID- 9606993
TI  - Expression of CD3 epsilon, CD3 zeta, and RAG-1/RAG-2 in decidual CD56+ NK cells.
AB  - In early pregnancy the uterine mucosa, the decidua, is infiltrated by numerous
      CD56bright, CD16- natural killer (NK) cells. In this paper we have shown that
      unlike adult peripheral blood NK cells these uterine NK cells express cytoplasmic
      CD3 and CD3 zeta, but CD3 gamma and CD3 delta were not found in the majority of
      cells. In contrast to previous reports, there was no evidence of RAG-1 nor RAG-2
      expression in decidual NK cells. These findings have implications for the
      ontogeny and development of decidual NK cells.

PMID- 9606994
TI  - NK cell granule exocytosis and cytokine production inhibited by Ly-49A
      engagement.
AB  - MHC class I-specific NK cell receptors inhibit natural killing, and presumably
      granule exocytosis, when engaged by target cell ligands but it is not yet known
      which specific activation receptor pathway for natural killing is inhibited or if
      these receptors influence other NK cell activities such as cytokine production.
      Moreover, an individual NK cell may express multiple inhibitory MHC class I
      receptors; these NK cell receptors may cooperate in inhibiting NK cell activity.
      To address these issues, we examined whether the murine Ly-49A NK cell receptor,
      specific for H-2Dd, can regulate granule exocytosis and NK cell cytokine
      responses. Expression of transfected H-2Dd on tumor targets specifically
      inhibited granule release from Ly-49A+ NK cells. Importantly, Ly-49A engagement
      also inhibited target cell-induced cytokine (GM-CSF) secretion. Using a target
      cell-free system, we next determined that anti-Ly49A mAb can regulate NK cell
      responses induced by specific stimuli. Cross-linking of NK1.1 with immobilized
      mAb induced granule release and TNF-alpha, IFN-gamma, and GM-CSF secretion; all
      were inhibited by coimmobilized anti-Ly-49A. These effects were specific because
      an isotype-matched control mAb did not alter NK1.1-mediated responses. Therefore,
      these results demonstrate that the Ly-49A receptor can regulate granule
      exocytosis and cytokine secretion in response to targets and NK1.1 signaling,
      consistent with its function as an inhibitory receptor for MHC class I molecules
      in NK cell-mediated cytotoxicity. In addition, these results strongly support the
      thesis that signals transduced from Ly-49A alone are sufficient for mediating the
      inhibitory effects against target cells.

PMID- 9606995
TI  - Substance P diminishes lipopolysaccharide and interferon-gamma-induced TGF-beta 1
      production by cultured murine macrophages.
AB  - Recent evidence has demonstrated the importance of substance P and its receptor
      in macrophage-mediated inflammatory responses. While previous studies have shown
      that substance P can augment proinflammatory monokine production, little is known
      about the effects of this neuropeptide on the production of monokines that might
      limit inflammation. In the present study we have investigated the effect of
      substance P treatment on the production of transforming growth factor-beta 1 (TGF
      beta 1) in cultured murine macrophages. We report that, while substance P agonist
      alone elicited increases in TGF-beta 1 mRNA expression and modest increases in
      TGF-beta 1 secretion, substance P dramatically diminished LPS- or IFN-gamma
      induced TGF-beta 1 production. These results suggest a previously unrecognized
      mechanism where substance P may act as a proinflammatory mediator by limiting the
      production of excessive levels of TGF-beta 1 by LPS- or IFN-gamma-activated
      macrophages.

PMID- 9606996
TI  - Interleukin-12 restores dendritic cell function and cell-mediated immunity in
      retrovirus-infected mice.
AB  - The effects of IL-12 treatment on the defects in DC function and on the reduced
      cell-mediated immunity induced in mice infected with Rauscher leukemia virus
      (RLV) were studied. DC from RLV-infected mice failed to stimulate significant
      allogeneic T cell proliferation but T cells from RLV-infected mice showed normal
      responses to allogeneic DC. In RLV-infected mice treatment with 5 doses of 100 or
      300 ng IL-12 around the time of infection resulted in DC that stimulated normal T
      cell proliferation. Treatment of mice with 300 ng IL-12 but not 100 ng reduced T
      cell responses. RLV-infected mice showed reduced delayed hypersensitivity to a
      contact sensitizer. Infected animals receiving the low dose of IL-12 which
      allowed normal DC and T cell function gave normal delayed hypersensitivity
      reactions; IL-12 thus resulted in both normal T cell stimulation by DC and cell
      mediated immunity. A failure of T cell stimulation by DC is associated with
      immunosuppression in retrovirus infection and the enhanced capacity of DC to
      stimulate T cells after IL-12 treatment may be beneficial.

PMID- 9606997
TI  - Altered macrophage intracellular signaling induced by protein-calorie
      malnutrition.
AB  - Protein-calorie malnutrition (PCM) contributes to increased morbidity and
      mortality through impairment of host defense mechanisms and reduced macrophage
      function. The present study examined alterations in macrophage intracellular
      signaling associated with the impairment in host defense capabilities. Mice were
      randomized to either control (regular diet) or protein-free diets (PCM) and pair
      fed for 1 week. Following endotoxin stimulation, peritoneal macrophages from PCM
      mice produce significantly less TNF-alpha and IL-6 product and had significantly
      less cell-associated IL-6 when compared to macrophages from control mice.
      Similarly, macrophages from PCM mice had a significant reduction in mRNA levels
      for both TNF-alpha and IL-6. Other macrophage intracellular signaling mechanisms,
      such as calcium flux and tyrosine kinase phosphorylation were also altered by
      PCM. The etiology of PCM-induced defects in macrophage function and intracellular
      signaling remain unknown but may be related to the neuroendocrine response to
      PCM.

PMID- 9606998
TI  - Immunological consequences of intervention in established immune responses by
      feeding protein antigens.
AB  - The usual result of feeding protein antigens to naive animals is the induction of
      profound immunological unresponsiveness and this is currently being exploited to
      treat inflammatory disease. Because the most useful therapeutic application of
      feeding antigen would be to suppress established disease, the aim of this study
      was to compare the immunological basis of oral tolerance induced by feeding a
      model antigen to naive and primed animals. We show that feeding 2-200 mg
      ovalbumin (OVA) to mice 7 days after immunisation with OVA in adjuvant produces
      dose-dependent suppression of delayed-type hypersensitivity (DTH), T cell
      proliferation, and both TH1 and TH2 cytokines, although serum IgG levels were
      unaffected. Feeding OVA before immunisation suppressed all these responses.
      Although feeding up to 8 days after immunisation could suppress some subsequent
      responses, tolerance was induced much more effectively when antigen was fed in
      the first 4 days after immunisation. Tolerance in primed mice was intact in IL-4
      /- mice, indicating that it was not caused by selective upregulation of TH2 cells
      in vivo. We conclude that oral administration of protein antigen can inhibit
      ongoing responses by all effector T cell subsets, but the exact consequences, and
      therefore possibly the mechanisms, are different from those induced by tolerising
      naive mice. These findings may have important implications for designing
      therapeutic regimes exploiting oral tolerance.

PMID- 9606999
TI  - CD4+ and CD8+ cell cytokine profiles in neonates, older children, and adults:
      increasing T helper type 1 and T cytotoxic type 1 cell populations with age.
AB  - The growing body of evidence suggestive of T helper types 1 and 2 (Th1/Th2)
      including their counterparts T cytotoxic types 1 and 2 (Tc1/Tc2) cell responses
      during various human disease states necessitates determination of normal T cell
      subsets' cytokine profiles. We show here, using intracellular cytokine staining
      and flow cytometry, that in healthy subjects interferon (IFN)-gamma producing
      CD4+ (Th1) and CD8+ (Tc1) cell populations progressively increase with age with
      strong correlation to CD45RO surface antigen expression. Meanwhile populations of
      cells capable of producing IL-4 (Th2 and Tc2) are comparably minimal across all
      age groups. Collectively, these results may reflect the maturation and expansion
      of Th1 and Tc1 cell populations from the neonatal period to adulthood, most
      probably dependent on antigen exposure.

PMID- 9607000
TI  - Downregulation of insulin-like growth factor-1 receptor (IGF-1R) expression in
      human T lymphocyte activation.
AB  - Although it is known that IGF-1 increases T lymphocyte proliferation, the
      regulation of its receptor expression during the process has not been defined.
      Consequently the regulation of IGF-1R expression by IGF-1 and the activation
      events in human blood T lymphocytes and the Jurkat T cell line were now
      investigated. IGF-1R expression in nonstimulated Jurkat cells was confirmed and
      downregulation by IGF-1 was demonstrated. In addition, both cell types showed a
      time-dependent reduction in the number of IGF-1R-positive cells following
      activation, which was increased by IGF-1. In Jurkat cells the negative regulation
      of IGF-1R levels was correlated with the appearance and continuous increase in IL
      2R. In T lymphocytes the decrease in IGF-1R expression was faster, reaching its
      plateau after 3 h of activation. Our findings suggest that loss of the IGF-1R is
      one of the initial events of the activation process not regulated by IL-2.

PMID- 9607001
TI  - Protection from primary infection and establishment of latency by vaccination
      with a herpes simplex virus type 1 recombinant deficient in the virion host
      shutoff (vhs) function.
AB  - A herpes simplex virus type 1 (HSV-1) recombinant virus deficient in the virion
      host shutoff (vhs) function was assessed for its ability to function as a live
      attenuated vaccine. Protection of mice from wild-type challenge infection and the
      establishment and reactivation of HSV-1 latency was measured in a mouse ocular
      model. Challenge virus replication in corneas and trigeminal ganglia was
      significantly reduced for vaccinated mice. Consistent with these findings, the
      vaccinated groups showed no clinical signs during acute infection and high levels
      of virus-specific IgG and neutralizing antibodies were induced. The establishment
      of and reactivation from latency in trigeminal ganglia from the vaccinated group
      were also significantly reduced relative to controls. These data suggest that vhs
      deletion mutants may have significant utility as live-attenuated HSV-1 vaccines.

PMID- 9607002
TI  - Postexposure vaccination with a virion host shutoff defective mutant reduces UV-B
      radiation-induced ocular herpes simplex virus shedding in mice.
AB  - A herpes simplex virus type 1 (HSV-1) recombinant (UL41NHB) deficient in the
      virion host shutoff (vhs) function was tested as a therapeutic vaccine in an
      ultraviolet (UV) light-induced mouse ocular reactivation model. Mice were
      infected with HSV-1 via the cornea. Following the establishment of latency by HSV
      1 the mice were subsequently vaccinated intraperitoneally with one dose of
      UL41NHB or with uninfected cell extract. Mice were subsequently UV-irradiated to
      induce viral reactivation and during the 7 days post-UV irradiation, numbers of
      mice shedding virus were reduced from 13/23 (57%) to 3/25 (12%), and numbers of
      virus-positive eye swabs were reduced from 40/161 (25%) to 6/175 (3%) by the
      vaccine (P < 0.001). These data suggest that deletion of vhs may be a useful
      strategy in the development of attenuated therapeutic HSV vaccines.

PMID- 9607003
TI  - Epitope specificity of antibodies raised against enterotoxigenic Escherichia coli
      CFA/I fimbriae in mice immunized with naked DNA.
AB  - The cfaB gene, coding for the CFA/I fimbrial adhesin of enterotoxigenic
      Escherichia coli (ETEC), was cloned and expressed as a fusion peptide with the
      glycoprotein D (gD) from herpes simplex virus type 1 (HSV) in the pRE4 eukaryotic
      expression vector, resulting in the recombinant plasmid pRECFA. All BALB/c mice
      injected intramuscularly (i.m.) with a single dose (100 micrograms) of the
      purified plasmid developed antibodies against epitopes found on dissociated CFA/I
      subunits as well as other homologous ETEC fimbriae. Surface-exposed epitopes
      found on intact CFA/I fimbriae were also recognized by antibodies derived from
      DNA immunization, but they did not overlap with those generated with purified
      CFA/I fimbriae. None of the sera raised in mice immunizated with pRECFA were able
      to agglutinate bacterial cells or inhibit haemagglutination promoted by CFA/I
      bearing ETEC cells. These results show that pRECFA can elicit CFA/I-specific
      antibodies, which may have different epitope specificities and functional
      properties compared with those generated with purified bacterial protein.

PMID- 9607004
TI  - Nitric oxide induction in murine macrophages and spleen cells by whole-cell
      Bordetella pertussis vaccine.
AB  - Nitric oxide (NO) induction was studied in the peritoneal macrophages and spleen
      cells of female NIH mice immunised with whole cell Bordetella pertussis vaccines
      of moderate and high potency, respectively. Compared with controls receiving
      diluent only, the macrophages and spleen cells of the vaccinated mice developed
      high levels of reactive nitrogen intermediates from the third day after
      injection. The nitrite concentrations achieved maximum values at the 10th day,
      but significant levels persisted until the 25th day. Heat-killed B. pertussis
      cells were the most effective inducer of NO synthesis, followed by
      lipopolysaccharide and agglutinogens Fim 2 and 3. Pertussis toxoid, filamentous
      haemagglutinin and pertactin were poor inducers of NO synthesis. The specific
      nitric oxide synthase inhibitor, aminoguanidine, and anti-IFN-gamma antibody
      blocked formation of nitrite by the macrophages and spleen cells. The production
      of NO in response to in vitro culture with bacterial antigen was clearly
      associated with protective immunity in vivo as determined by i.c. challenge.
      These results suggest that reactive nitrogen intermediates play a role in the
      immune response induced by whole cell pertussis vaccines.

PMID- 9607005
TI  - Immunosuppression and nitric oxide production induced by parenteral live
      Salmonella vaccines do not correlate with protective capacity: a phoP::Tn10
      mutant does not suppress but does protect.
AB  - Previous work from our laboratory showed that an aroA mutant strain of S.
      typhimurium, SL3235, induces profound immunosuppression 7 days post-parenteral
      inoculation, and that the suppression is mediated by nitric oxide. Suppression
      was measured by the capacity of spleen cells to mount a primary in vitro plaque
      forming cell response to sheep red blood cells in Mishell-Dutton cultures. In the
      present studies, the capacity of a panel of strains of attenuated Salmonella with
      various genetic lesions was tested. Most of the strains were S. typhimurium, but
      several were S. dublin. It was found that a variety of Salmonella strains induced
      suppression, demonstrating that suppressive capacity is not unique to SL3235 or
      to S. typhimurium. A strong correlation was obtained between the log10 of the
      microbial burden (cfu spleen-1) on the seventh day post-vaccine inoculation and
      the degree of immunosuppression. Strains that gave high spleen counts gave
      greater suppression. Microbial burden also correlated with the size of the spleen
      and the amount of nitrite produced by spleen-cell cultures, a measure of nitric
      oxide. Finally, the degree of immunosuppression was found to be linearly related
      to the log10 of the amount of nitrite produced. The capacity of the various
      strains of Salmonella to protect against challenge with virulent S. typhimurium,
      strain W118-2, was also tested. No correlation was found between suppressive and
      protective capacities of the various strains. Two strains suppressed, but did not
      protect. While most strains that protected grew or persisted in vivo, a
      phoP::Tn10 mutant of S. typhimurium did not grow or persist; this phoP mutant did
      not cause immunosuppression, but gave 100% protection against challenge with wild
      type S. typhimurium, suggesting that such mutants have advantageous properties as
      live vaccines.

PMID- 9607006
TI  - Protection against Helicobacter pylori infection in mice by intragastric
      vaccination with H. pylori antigens is achieved using a non-toxic mutant of E.
      coli heat-labile enterotoxin (LT) as adjuvant.
AB  - We have previously shown that infection of mice with H. pylori can be prevented
      by oral immunization with H. pylori antigens given together with E. coli heat
      labile enterotoxin (LT) as adjuvant. Since LT cannot be used in humans because of
      its unacceptable toxicity, we investigated whether protection of mice could be
      achieved by co-administration of antigens with non-toxic LT mutants. Here we show
      that CD1/SPF mice are protected against infection after oral vaccination with
      either purified H. pylori antigens (native and recombinant VacA, urease and
      CagA), or whole-cell vaccine formulations, given together with the non-toxic
      mutant LTK63 as a mucosal adjuvant. Furthermore we show that such protection is
      antigen-specific since immunization with recombinant or native VacA plus LTK63
      conferred protection against infection by an H. pylori Type I strain, which
      expresses VacA, but not against challenge with a Type II strain which is not able
      to express this antigen. These results show that: (1) protection against H.
      pylori can be achieved in the mouse model of infection using subunit recombinant
      constructs plus non-toxic mucosal adjuvants; and (2) this mouse model is an
      useful tool in testing H. pylori vaccine formulations for eventual use in humans.

PMID- 9607007
TI  - Immunogenicity of chimeric multiple antigen peptides based on Plasmodium
      falciparum antigens: impact of epitope orientation.
AB  - Assembly of B and T epitopes in multiple antigen peptides (MAP) can bypass
      genetically predisposed unresponsiveness to B epitopes. Although the underlying
      mechanisms are unknown, B-cell responses to such diepitope MAP are influenced by
      intramolecular epitope orientation. In this study, MAP constructs were
      synthesized, encompassing two epitopes derived from the Plasmodium falciparum
      antigens circumsporozoite protein (CS) and Pf332. In addition to B epitopes, the
      sequences comprised T epitopes restricted to mouse H-2b (CS) or to H-2d and H-2k
      (Pf332) haplotypes. Congenic H-2b, H-2d and H-2k Balb mice were immunized with
      MAP in which the two epitopes were arranged either tandemly or in parallel.
      Tandemly arranged (B-T)4 MAP, in which the relevant T epitope was positioned
      adjacent to the lysine core [(Pf332-CS)4-core for H-2b mice and (CS-Pf332)4-core
      for H-2d and H-2k mice], elicited the most potent antibody responses in terms of
      reactivity to both epitopes. Additionally, the (B-T)4 constructs were generally
      most efficient in recalling proliferative T-cell responses in vitro, irrespective
      of the MAP used for in vivo priming. As high antibody titers were generated to
      both epitopes, the position of B epitopes in the constructs does not appear to be
      critical for an efficient B-cell response. Rather, the association of strong B-
      and T-cell responses to the (B-T)4 MAP constructs suggests that the
      intramolecular position of the relevant T epitope determines the magnitude of
      specific antibody production.

PMID- 9607008
TI  - Immune responses in calves immunised orally or subcutaneously with a live
      Salmonella typhimurium aro vaccine.
AB  - Salmonella aro vaccines are able to confer solid protection against homologous
      virulent challenge in several animal species. Calves were protected against
      virulent S. typhimurium challenge following administration of a single oral dose
      of live BRD562 vaccine. Immune responses elicited by the S. typhimurium aro
      vaccine strain BRD562 were studied following administration to calves by either
      the oral or subcutaneous route. Serum antibodies to Salmonella polypeptides,
      following oral or subcutaneous vaccination, were detected by immunoblotting and
      the route of inoculation found to affect both the antibody isotype and the
      antigens detected. Oral, but not subcutaneous, immunisation induced bovine serum
      IgA antibodies against Salmonella antigens of 30 kDa and 65 kDa and bovine IgG2
      antibodies against a 35 kDa antigen. Subcutaneous vaccination triggered responses
      against antigens of 52 kDa, 54 kDa and 57 kDa which were not detected by immune
      plasma of animals immunised orally. Antibody responses to LPS were poor in
      animals inoculated by either route. Subcutaneous vaccination elicited T-cell
      responses against Salmonella antigens as measured by in vitro peripheral blood
      cell thymidine incorporation. These studies show that the S. typhimurium vaccine
      strain BRD562 is capable of inducing both humoral and cellular immune responses.
      Further studies are necessary to identify the nature of the antigens responsible
      for protection. Oral or subcutaneous inoculation of BRD562(pTETnir15) failed to
      induce serum antibodies against the fragment C of tetanus toxin (TetC) but was
      effective in mice. Oral vaccination with this recombinant vaccine induced mucosal
      IgA against TetC. This is the first time that Salmonella recombinant vaccines
      have been shown to successfully elicit antibodies against a guest antigen in
      cattle after one single oral inoculation.

PMID- 9607009
TI  - The efficacy of an experimental oil-adjuvanted encephalomyocarditis vaccine in
      elephants, mice and pigs.
AB  - An oil-adjuvanted inactivated encephalomyocarditis (EMC) vaccine was developed to
      protect a wild population of elephants against a natural outbreak of disease. The
      experimental vaccine was initially tested for efficacy by challenging mice and
      pigs. Mice showed protection against challenge and pigs developed high antibody
      levels. Since both vaccinated and control pigs failed to develop clinical
      disease, apparently due to the low virulence of the strain in this species,
      protection in pigs could not be evaluated. Vaccinated elephants developed high
      antibody titers which protected all vaccinates from a challenge roughly two
      months post-vaccination, whereas controls developed fatal or sub-clinical
      myocarditis. This is the first report of an inactivated EMC vaccine inducing high
      antibody titers in domestic and wild animal species. Due to the potency of this
      vaccine and the acceptability of the oil adjuvant used, it has potential for use
      in animals in zoological collections as well as in the pig industry.

PMID- 9607010
TI  - An efficacy trial of the malaria vaccine SPf66 in Gambian infants--second year of
      follow-up.
AB  - In 1994, 630 Gambian infants were immunized with three doses of the synthetic
      polypeptide malaria vaccine SPf66 or with a control vaccine. No significant
      protection against first or total attacks of malaria was observed among the
      children who received SPf66. However, the period of follow-up was short. Thus,
      532 children were followed for a second malaria transmission season during which
      291 episodes of malaria were detected. Protective efficacies of SPf66 against
      first attacks of malaria and against all attacks of malaria were 8% [95% CI-20%,
      30%] and 2% [95% CI-26% 24%] respectively. SPf66 did not provide any significant
      degree of protection to Gambian infants during a second year of follow-up.

PMID- 9607011
TI  - Two patterns of systemic immediate-type reactions to Japanese encephalitis
      vaccines.
AB  - We have found two different patterns of systemic immediate-type reactions to
      Japanese encephalitis vaccine containing gelatin as the stabilizer. One group of
      affected children had cutaneous and respiratory symptoms (e.g., systemic
      urticaria and wheezing) and the other group had cardiovascular symptoms (e.g.,
      hypotension and cyanosis) without cutaneous and respiratory symptoms. The
      children in the former group had anti-gelatin IgE in their sera, whereas those in
      the latter group did not. We think that the two patterns may be caused by
      different mechanisms or different allergens.

PMID- 9607012
TI  - Factors influencing immunity against diphtheria in adults.
AB  - In about 50% of all adult Germans, serological immunity to diphtheria is lacking
      even though a vaccination history exists in most cases. In this study, the
      factors contributing to diphtheria immunity, up to 43 years after the last
      diphtheria vaccination, were analysed. Serum samples were taken from 287 adults
      whose complete vaccination history was available, and who had received a standard
      primary vaccination. The sera were tested by tissue culture neutralization assay
      for diphtheria antitoxin levels. The time lapse since the last diphtheria
      vaccination proved to be the most important factor influencing the protection
      rate. Secondly, the factor last vaccination within the first 3 years of life and,
      finally, female gender were found to correlate significantly with a low
      protection rate. No direct effect could be established for age, number of
      previous vaccinations, occupational contact with patients or travel within any
      endemic region during the last 10 years. Since diphtheritic infection can occur
      among previously vaccinated persons, the immunity gap observed among adults
      should be closed by regular diphtheria boosters. Special attention should be paid
      to the three groups mentioned. Further investigation is required to determine
      whether or not a single booster vaccination is sufficient to provide long-term
      protection for those in the risk groups indicated above.

PMID- 9607013
TI  - Mitogenic synthetic polynucleotides suppress the antibody response to a bacterial
      polysaccharide.
AB  - Unmethylated bacterial DNA containing a high frequency of the CpG motif, is
      mitogenic and induces T-cell independent, murine B-cell proliferation. These
      stimulatory effects are also induced by synthetic oligonucleotides that contain
      one or more unmethylated CpG dinucleotides (CpG oligo). Such mitogenicity is not
      seen with highly methylated vertebrate DNA, which has a lower prevalence of the
      CpG motif than bacterial DNA. Due to their stimulatory effects, CpG oligo have
      been proposed for use as vaccine adjuvants. In order to determine if a synthetic
      CpG oligo that was stimulatory for B-cell proliferation could augment the murine
      antibody response to protective bacterial polysaccharide epitopes (Pseudomonas
      aeruginosa LPS-O polysaccharide side chain; high-molecular-weight polysaccharide
      or high-MW PS), BALB/c mice were injected with mitogenic doses of CpG oligo
      simultaneously with high-MW PS, and antibody titers were measured by ELISA weekly
      for 4 weeks. Controls received PBS, a nonstimulatory control oligo plus PS, CpG
      alone, or PS alone. Despite evidence of B-cell mitogenicity and an increase in
      total IgM in CpG oligo-treated mice, CpG oligo treatment plus PS significantly
      decreased the high-MW PS antibody response compared to PS alone. The blunting of
      the anti-PS antibody response could be eliminated by vaccinating the animals with
      PS prior to CpG oligo. We conclude that despite in vitro and in vivo evidence of
      B-cell proliferation, this CpG oligo reduces PS-specific antibody responses in an
      animal model when given simultaneously with a bacterial polysaccharide. Based on
      results in this model, oligonucleotides containing stimulatory unmethylated CpG
      dinucleotides may not be useful adjuvants when given simultaneously with
      bacterial PS vaccines.

PMID- 9607014
TI  - Serum antibody responses of weanling mice and two-year-old children to
      pneumococcal-type 6A-protein conjugate vaccines of differing saccharide chain
      lengths.
AB  - Type 6A pneumococcal polysaccharide (PS) fractions having mean lengths 2, 7, or
      14 repeat units were coupled to tetanus toxoid, giving conjugates T-6A-2, T-6A-7
      or T-6A-14. In weanling outbred mice, type-6A serum antibody responses were
      minimal to T-6A-7 but significantly higher to T-6A-2 and T-6A-14. In contrast,
      two-year-old humans responded increasingly to T-6A-2, T-6A-7, and T-6A-14; type
      6B antibody rose, but variably. Upon challenge with 6B PS at age 3 yr, conjugate
      primed children made anamnestic responses. T-6A-14, containing the longest
      saccharide chains (and highest saccharide:protein mass ratio) excelled in priming
      as well as antibody induction.

PMID- 9607015
TI  - Poly[di(carboxylatophenoxy)phosphazene] (PCPP) is a potent immunoadjuvant for an
      influenza vaccine.
AB  - The adjuvant activity of poly[di(carboxylatophenoxy)phosphazene] (PCPP) on the
      immunogenicity of formalin-inactivated influenza virions and commercial trivalent
      influenza vaccine was studied. Regardless of which antigen preparation is used,
      the addition of 100 micrograms PCPP enhances the HAI antibody response 10-fold
      over the levels elicited by the vaccine alone. Similarly, PCPP enhanced the IgM,
      IgG, and IgG1 ELISA antibody titers to influenza antigens at least 10-fold higher
      than the vaccine alone. In contrast, the IgG2a isotype titers were only enhanced
      about 2-fold. Immunization of aged mice (22 months old) with trivalent influenza
      vaccine alone did not sero-convert these mice as measured by HAI or ELISA whereas
      significant sero-conversion was achieved when mice were immunized with PCPP
      formulated trivalent vaccine. The adjuvant activity of PCPP was shown to not be
      due to a site of injection depot effect. PCPP adjuvanticity was positively
      correlated to the molecular weight of the polymer.

PMID- 9607016
TI  - Novel adjuvants for induction of T-cell and antibody responses to
      encephalitogenic and regulatory determinants in Lewis rats.
AB  - Treatment of human autoimmune diseases may be enhanced by using adjuvants that
      can selectively induce immunoregulatory responses. Two versions of a novel
      nonionic block copolymer adjuvant suitable for human use, Optivax Oil Formulation
      (OF) and Optivax Aqueous Formulation (AF), were evaluated for induction of
      immunity to encephalitogenic and regulatory T-cell receptor (TCR) V-gene
      determinants. In Lewis rats immunized with myelin basic protein (BP), Optivax OF
      was more efficient than Optivax AF for inducing delayed type hypersensitivity
      (DTH), T-cell proliferation, antibodies, and even mild clinical signs of
      experimental autoimmune encephalomyelitis (EAE). Similarly, Optivax OF was more
      efficient for inducing inflammatory T-cell and antibody responses to
      immunoregulatory V beta 8.2 proteins and peptides than Optivax AF, which induced
      a noninflammatory Th2 response. In general, DTH response to the various
      immunogens was reflected by increased cellularity and mRNA levels for IFN-gamma
      in draining lymph nodes, whereas LN cell proliferation without DTH was
      characterized by increased IL-2 mRNA levels but low or absent IFN-gamma message.
      These data suggest important differential adjuvant effects of Optivax OF versus
      Optivax AF on the respective induction of Th1 versus Th2 responses that may be
      useful in the selective treatment of human immune disorders.

PMID- 9607017
TI  - Randomised controlled trial of combined diphtheria, tetanus, whole-cell pertussis
      vaccine administered in the same syringe and separately with Haemophilus
      influenzae type b vaccine at two, three and four months of age.
AB  - An open randomised controlled multicentre study compared the immunogenicity and
      reactogenicity of three vaccines given by injection at two, three and four months
      of age. Children (89) received Haemophilus influenzae type b (Hib) vaccine
      (SmithKline Beecham Biologicals [SB]) administered in the same syringe with
      combined diphtheria-tetanus-whole-cell pertussis (DTPw) vaccine (Evans); 75
      received Hib vaccine (SB) administered as a separate injection with DTPw vaccine;
      66 received Hib vaccine (Pasteur Merieux [PM]) administered as a separate
      injection with DTPw vaccine. All subjects in both groups receiving Hib (SB)
      vaccine had levels of antibodies to the Hib polysaccharide polyribosylribitol
      phosphate (PRP) greater than 0.15 microgram ml-1 as did 97% of those receiving
      Hib (PM) vaccine 1 month after administration of the final vaccine dose. Subjects
      in all three groups demonstrated an immunological response to pertussis,
      diphtheria and tetanus antigens. The geometric mean titres of the group given Hib
      (SB) and DTPw vaccine mixed in the same syringe were lower than the other groups.
      There were no apparent differences between the treatment groups in the incidence
      of local or systemic reactions, or serious adverse events. This study has
      confirmed that it is possible to halve the number of injections necessary to
      offer protection, with advantages to parents, children, doctors and nurses, using
      a combined DTPwHib vaccine and in accordance with the UK's accelerated primary
      immunisation schedule at two, three and four months of age.

PMID- 9607018
TI  - Gene gun particle-mediated vaccination with plasmid DNA confers protective
      immunity against rabies virus infection.
AB  - Accell gene gun particle-mediated immunization with DNA encoding the glycoprotein
      gene of the challenge virus standard strain of rabies virus was evaluated for its
      ability to elicit protective levels of serum anti-rabies virus neutralizing
      antibody. Strong primary and booster neutralizing antibody responses were
      detected in mice following immunization with 2 micrograms of DNA coated on 2.6
      micron gold beads. Protective levels of antibody persisted for over 300 days.
      Mice challenged intraplantarly 315 days post-primary immunization (225 days post
      booster vaccination) survived lethal rabies virus challenge. Our data demonstrate
      a potentially significant role for gene gun-based delivery of DNA in the field of
      rabies virus vaccination.

PMID- 9607019
TI  - Characterization of highly purified, inactivated HIV-1 particles isolated by
      anion exchange chromatography.
AB  - This report characterizes inactivated, gp120 depleted, HIV-1 particles purified
      by an anion exchange chromatography production process. This antigen formulated
      with incomplete Freund's adjuvant constitutes Remune, which is being evaluated in
      a phase III clinical endpoint trial to determine the effect of this immune-based
      therapy on clinical progression of HIV-1 seropositive patients. Multiple
      production lots of the inactivated HIV-1 antigen strain HZ321, isolated by anion
      exchange chromatography, exhibit purity of > 95% by gel filtration. These
      findings are corroborated by thin section electron microscopy showing a
      homogenous field of intact particles. Analyses of the purified virus particles
      for protein, lipid, carbohydrate and RNA show structural retention of the
      envelope proteins, lipid bilayer and core components after large scale
      processing. The qualitative identification of at least 85% of total HIV-1 protein
      is determined by ELISA, Western blot, HPLC and amino acid sequencing analyses.
      Quantitative values are assigned to 50% of these proteins. The data confirm the
      presence of virally encoded proteins p6, p7, pI15, p17, p24, p32, pI39Gag, gp41,
      pp55Gag, p66/51, Vpr, Vif and Nef. Excellent consistency between production lots
      and equivalency to HIV-1 preparations purified by sucrose density gradient
      sedimentation has been established for protein and lipid composition, and overall
      purity. These findings further establish that non-viral encoded proteins and
      lipids are integral structural components of the intact virion and are not
      contaminants unique to a particular isolation method. The data confirm the
      presence of multicomponent antigens in the viral particles for stimulating a
      broad HIV-1 specific immune response. Finally, the work demonstrates that the two
      inactivation procedures (beta-propiolactone and gamma irradiation), which achieve
      efficient viral inactivation meeting US FDA guidelines, do not damage the protein
      antigens of the viral particles.

PMID- 9607020
TI  - Comparison of DNA application methods to reduce BRSV shedding in cattle.
AB  - We compared the protection afforded by three different DNA application methods
      against bovine respiratory syncytial virus (BRSV) infection in cattle. A
      synthetic gene that codes for the G protein of BRSV was inserted into a
      eukaryotic vector and was used in the vaccine. Intradermal (i.d.) application
      with a needleless injector (NI), the Pigjet, reduced BRSV excretion significantly
      better after BRSV challenge than intramuscular (i.m.) or i.d. vaccination with a
      needle. Serum antibodies against the G protein were consistently the highest and
      showed less variation in Calves vaccinated with the NI compared with those in
      i.m. and i.d. vaccinated calves. After BRSV challenge, secondary serum and
      mucosal antibody responses were also the highest in NI vaccinated calves. We
      conclude that DNA application with the needleless injector is substantially
      better than i.m. or i.d. application, and is capable to prime the immune response
      at the respiratory mucosa.

PMID- 9607021
TI  - Protection against measles virus-induced encephalitis by antibodies from mice
      immunized intranasally with a synthetic peptide immunogen.
AB  - Balb/c mice were immunized intranasally (i.n.) with a chimeric synthetic peptide
      containing two copies of a T- and one copy of a B-cell epitope (TTB) from measles
      virus (MV) fusion protein, plus cholera toxin B (CTB) adjuvant. The antibodies
      induced cross-reacted with, and neutralized MV and on passive transfer, protected
      mice against encephalitis induced by neuroadapated MV. Immunization with TTB
      alone induced antibodies which increased survival but not significantly compared
      to controls. Furthermore, i.n. immunization with TTB plus CTB induced TTB
      specific IgA antibodies in saliva and nasal washes. Co-administration of CTB
      increased the affinity of antibodies to the B-cell epitope of TTB and caused a
      relative increase in the level of anti-peptide antibodies of the IgG2a subclass
      and the overall titre of IgG antibodies. These results indicate the potential of
      the i.n. route for immunization with synthetic peptide immunogens for induction
      of both local and systemic anti-peptide antibody responses.

PMID- 9607022
TI  - Safety and immunogenicity of REMUNE in HIV-infected Thai subjects.
AB  - The safety and immunogenicity of REMUNE, an HIV-specific immune based therapy for
      HIV infection, was evaluated in a cohort of 30 HIV infected subjects in Thailand.
      This therapy utilizes a gp120 depleted inactivated virus (HZ321), which exhibits
      a high degree of conservation with the core antigens of both type B' and E
      strains of HIV, the predominant Thailand isolates. The treatment was well
      tolerated, with no serious adverse events reported over the course of the 4-month
      trial. Treatment in which four doses were administered with REMUNE appeared to
      boost HIV-specific immune responses, with approximately 75% of the treated
      subjects demonstrating an increase in either the repertoire or the intensity of
      the serological response to HIV as measured by Western blot. CD4%, viral load,
      and weight remained stable over the course of the 4-month study relative to
      baseline values. Viral subtyping of this cohort revealed a predominance of type
      'E'. These data suggest that REMUNE is safe and immunogenic in seropositive Thai
      subjects and supports further study of the therapeutic potential of REMUNE to
      treat HIV-1 infection.

PMID- 9607023
TI  - Recombinant cholera toxin B subunit acts as an adjuvant for the mucosal and
      systemic responses of mice to mucosally co-administered bovine serum albumin.
AB  - We examined the mucosal adjuvant activity of recombinant cholera toxin B subunit
      (rCTB) produced by Bacillus brevis carrying pNU212-CTB by intranasal or oral co
      administration of bovine serum albumin (BSA). Intranasal administration
      stimulated a high level of BSA-specific serum IgG antibody response and BSA
      specific IgA antibody responses in the nasal and pulmonary lavages. Oral
      administration induced a moderate level of BSA-specific serum IgG antibody and a
      low level of BSA-specific IgA antibody in the large intestinal washes. These
      results show that CTB alone can act as an intranasal or oral delivery carrier; it
      also has strong adjuvant properties for stimulating serum IgG and mucosal IgA
      immune responses to unrelated, non-coupled antigens after intranasal or oral co
      immunization.

PMID- 9607024
TI  - Systemic and local immune responses after parenteral influenza vaccination in
      juvenile diabetic patients and healthy controls: results from a pilot study.
AB  - Diabetes patients suffer frequent complications and some excess mortality after
      influenza virus infection. Despite widespread agreement that diabetic patients
      should be routinely vaccinated against influenza, some reports claim that
      diabetics have a poor immune response to influenza vaccine. We have performed a
      pilot study to examine the humoral immune response of juvenile diabetics and
      matched healthy controls vaccinated with inactivated trivalent influenza vaccine.
      By enzyme-linked immunospot assay we found that both groups had comparable
      magnitude and kinetics of influenza-specific antibody secreting cell response.
      The influenza-specific antibody response in both serum and oral fluid were
      similar for both groups, and also showing a kinetic profile in accordance with
      our earlier data for healthy adults. Our study did not detect a difference in the
      humoral immune response between juvenile diabetics and healthy controls.

PMID- 9607025
TI  - Protection of mice against SV40 tumours by Pam3Cys, MTP-PE and Pam3Cys conjugated
      with the SV40 T antigen-derived peptide, K(698)-T(708).
AB  - The intraperitoneal injection of Balb/c mice with synthetic analogues of
      adjuvants S-[2,3-bis(palmitoyloxy)-(2-RS)-propyl]-N-palmitoyl-R-cysteine
      (Pam3Cys) or muramyltripeptide phosphatidylethanolamine (MTP-PE) inhibited the
      tumourigenic growth of subcutaneously injected VLM cells, a syngeneic simian
      virus 40 (SV40)-transformed cell line. Furthermore, the Pam3Cys conjugate of K698
      T708 (KT), which represents the C-terminal undecapeptide of the SV40 large tumour
      (T) antigen, was tumour-protective. Also syngeneic spleen cells, preincubated in
      vitro with this Pam3Cys-KT derivative, which anchores spontaneously at the cell
      membrane, were, through SV40 tumour mimicry, tumour-protective. The protection
      was impaired by treatment of the mice with either anti-CD4, anti-CD8 IgG, anti
      asialo GM1 antiserum or dextrane sulfate, which deplete the CD4+, CD8+ and NK
      cells or the macrophages, respectively. In summary, SV40 tumour transplantation
      resistance can be experimentally elicited by a tumour-epitope-specific vaccine.
      In the absence of an immunogenic epitope protection was obtained by
      administration of biological response modifiers. Protection is effected by SV40-T
      antigen-specific cytotoxic lymphocytes in cooperation with NK cells and
      macrophages.

PMID- 9607026
TI  - Mutations in the 'a' determinant of hepatitis B surface antigen among Chinese
      infants receiving active postexposure hepatitis B immunization.
AB  - Twenty-four infants who became positive to the surface antigen of hepatitis B
      virus (HBsAg) despite a complete course of active postexposure immunization with
      plasma derived hepatitis B vaccine were studied. The polymerase chain reaction
      amplified products of the common neutralizing epitope 'a' determinant of HBsAg
      (Nucleotide 419-598) from serum samples were sequenced and analyzed for
      nucleotide mutations. Four cases (16.7%) had mutations that led to amino acid
      substitutions between codons 124 and 147. Only one case (N1) showed a
      substitution at codon 145 (from glycine to arginine, 145R), the other three were
      at codons 126-129. The mother of N1 was co-infected with the wild type and the
      mutant virus. Five years later, serum of N1 showed only the wild type virus.
      There was no significant relationship between the mutation rate and the anti-HBs
      response to hepatitis B vaccination. Results suggest that without immune
      selective pressure, 145R variant was not frequently observed, and was not stable.
      Mutation in the 'a' determinant was not an important cause of failure to prevent
      maternal-infant transmission of HBV by active postexposure hepatitis B
      immunization in Chinese children.

PMID- 9607027
TI  - Effect of route of immunisation and adjuvant on T and B cell epitope recognition
      within a streptococcal antigen.
AB  - Oral immunisation may elicit both systemic and mucosal immunity. Antibodies
      directed to a portion (residues 816-1213) of a cell surface adhesin termed
      streptococcal antigen I/II (SA I/II) of Streptococcus mutans prevent colonisation
      of this bacterium in vivo. This polypeptide is highly immunogenic in mice and is
      immunodominant in naturally sensitised humans. In this study, the effects of
      immunisation by different routes and of adjuvant on T and B cell epitope
      recognition were investigated. The recombinant polypeptide comprising residues
      816-1213 of SA I/II was administered to groups of SJL mice intraperitoneally,
      subcutaneously or orally. For systemic immunisation, incomplete Freund's adjuvant
      was used, whereas for oral immunisation the antigen was coupled to the cholera
      toxin B subunit. The hierarchy of T and B cell epitope recognition differed
      significantly following different routes of immunisation. These differences in T
      and B cell responses may be accounted for by extracellular protease activity and
      processing by antigen presenting cells at the sites of immunisation. Furthermore,
      epitope recognition may be critical if the immune response elicited by a vaccine
      must be directed specifically to functional determinants within an antigen. This
      study emphasises the importance of route of immunisation in vaccine development.

PMID- 9607028
TI  - Feline immunodeficiency virus subunit vaccines that induce virus neutralising
      antibodies but no protection against challenge infection.
AB  - Three experimental vaccines against feline immunodeficiency virus (FIV), all
      based on viral antigens presented via immune stimulating complexes (iscoms), were
      tested for their capacity to induce protection in cats from FIV infection. The
      respective vaccines consisted of FIV propagated in Crandell feline kidney (CrFK)
      cells (FIV-iscoms); FIV-iscoms spiked with recombinant vaccinia virus expressed
      FIV envelope glycoprotein incorporated into iscoms (FIV-iscoms + vGR657x15
      iscoms) and vGR657x15-iscoms spiked with recombinant FIV Gag protein incorporated
      into iscoms (vGR657x15-iscoms + FIV-Gag-iscoms). Simian immunodeficiency virus
      envelope glycoprotein incorporated into iscoms, iscoms prepared with uninfected
      CrFK cells, and PBS served as controls. All cats vaccinated with vGR657x15-iscoms
      combined with FIV-iscoms or FIV-Gag-iscoms developed Env-specific plasma antibody
      responses. These antibodies neutralised FIV infection in CrFK cells, but failed
      to neutralise FIV infection in primary feline thymocytes. FIV-iscoms induced poor
      Env-specific responses and only one out of six cats developed antibodies that
      neutralised FIV in the CrFK cell based assay. Four weeks after challenge all cats
      proved to be infected, showing that none of the vaccine preparations provided
      protection. In contrast, 2 weeks after infection, virus infected peripheral blood
      mononuclear cells were only observed in cats vaccinated with FIV-iscoms +
      vGR657x15-iscoms or CrFK-iscoms and to a lesser extent in cats vaccinated with
      FIV-iscoms and vGR657x15-iscoms + FIV-Gag-iscoms, but not in cats vaccinated with
      SIV-iscoms or PBS. The differences found in cell associated virus loads amongst
      the respective groups are discussed in the light of antibody mediated enhancement
      of infectivity and protective effects provided by Gag-specific T cell responses.

PMID- 9607029
TI  - Transdermal immunisation with an integral membrane component, gap junction
      protein, by means of ultradeformable drug carriers, transfersomes.
AB  - Molecules greater than 500 Da normally do not cross the skin. This prevents
      epicutaneous delivery of the high molecular weight therapeutics as well as non
      invasive transcutaneous immunisation. Extremely deformable vesicles prepared by
      the judicious combination of several materials provide a solution to this
      problem: the resulting agent carriers, transfersomes, are the only tested
      colloidal system that can transport even large macromolecules spontaneously
      through the skin in immunologically active form. Gap junction proteins (GJP)
      incorporated into transfersomes and applied to the intact skin surface thus give
      rise to specific antibody titres marginally higher than those elicited by
      subcutaneous injections of GJP in transfersomes, mixed lipid micelles or
      liposomes. The latter two carrier systems give no significant biological response
      after epicutaneous administration. Transcutaneous protein delivery by means of
      transfersomes also appears to increase the relative concentration of anti-GJP IgA
      in the serum.

PMID- 9607030
TI  - Influenza vaccination in a healthy geriatric population: preferential induction
      of antibodies specific for the H3N2 influenza strain despite equal T cell
      responsiveness to all vaccine strains.
AB  - Cellular as well as humoral immune reactivity were studied in healthy young (< 30
      years; n = 12) and older (> 65 years; n = 12) individuals before as well as 1
      month after immunization with a trivalent whole virus influenza vaccine. Before
      vaccination, peripheral blood mononuclear cell proliferation in response to in
      vitro stimulation with each of the virus strains was low in both groups. No
      antibodies against either the H1N1 or the B strain were found in most
      individuals, while 91% of the young and 75% of the elderly persons had low but
      protective antibody titres to the H3N2 strain. Vaccination led to a significant
      enhancement of peripheral blood mononuclear cell reactivity to all three
      influenza strains in both age groups. However, there was a significant difference
      in the humoral immune response between the groups. While there was a vigorous
      antibody response to all three vaccine strains among young persons, protective
      titres against the H1N1 and the B strains were only just reached in the old. In
      contrast, antibody production to the H3N2 strain was most abundant in the
      majority of elderly individuals, leading to significantly higher titres in the
      old than in the young group. In conclusion, the results demonstrate the
      preferential induction of antibodies to one particular influenza strain despite
      equal T cell recruitment to all vaccine strains in healthy aged individuals after
      immunization with a trivalent influenza vaccine. Our findings underline the
      complexity of immunological alterations to be expected after vaccination in
      healthy elderlies.

PMID- 9607031
TI  - Immunogenicity and protective role of three formulations of oral cholera vaccine.
AB  - Three formulations of oral cholera vaccine were compared with respect to their
      immunogenicity and protective ability in a rat ileal loop model. Eight-week-old
      Wistar rats were divided into five groups. The first group received orally
      vaccine A consisting of liposome-associated V. cholera lipopolysaccharide,
      fimbriae and procholeragenoid, whereas the rats of groups 2 and 3 received orally
      vaccines B and C consisting of heatkilled fimbriated and non-fimbriated whole
      cell V. cholerae, respectively. Rats of groups 4 and 5 were controls that
      received orally liposomes alone and normal saline solution, respectively. It was
      found that vaccine A elicited stronger immune responses to all three V. cholerae
      antigens. The antibody responses were detected in both serum and intestinal
      lavage samples. Vaccine B elicited only modest serum and intestinal responses to
      V. cholerae fimbriae (anti-F). No detectable immune response was found in rats of
      group 3 immunized with vaccine C. Rats immunized with vaccines A and B had a
      similar order of magnitude of numbers of vibrios adhered to their intestinal
      mucosa. These numbers were less than those associated with the intestinal tissues
      of control rats of groups 4 and 5 by about two orders of magnitude. Although
      without any detectable immune response, rats of group 3 that were immunized with
      vaccine C showed some reduction in numbers of vibrios associated with their
      intestinal mucosa. The numbers of vibrios recovered from the intestinal segments
      of rats of all treatment groups were in the order group 1 = 2 < 4 = 5. Electron
      micrography also revealed patches of vibrio colonization on the mucosa of rats of
      groups 3, 4 and 5. These features were not found in the groups vaccinated with
      vaccines A and B. The inhibition of vibrio colonization afforded by the vaccines
      was biotype- and serotype-non-specific. The results suggest that the heat-killed
      whole cell fimbriated V. cholerae may be an alternative vaccine preparation to
      the liposome-associated refined antigen vaccine at a lower cost.

PMID- 9607032
TI  - The mode of presentation and route of administration are critical for the
      induction of immune responses to p53 and antitumor immunity.
AB  - We have examined the immune response to full-length wild-type human p53 presented
      by a recombinant canarypox vector (ALVAC) and by plasmid DNA. For the ALVAC
      recombinant, intravenous, but not subcutaneous, intramuscular or intradermal
      administration, induced CD8+ CTLs that lysed tumor cells transfected with human
      mutant p53. Intrasplenic administration also induced CTLs. Biodistribution
      studies showed that intravenously injected ALVAC localized primarily in the lung,
      liver and spleen, whereas intramuscularly injected virus remained predominantly
      at the injection site. Intradermal and intramuscular immunization with naked
      plasmid DNA encoding human wild-type p53 also induced a specific CTL response.
      DNA immunization induced complete protection against challenge with a mouse
      embryo fibroblast transfected with human mutant p53 and partial, but significant,
      protection against a transfected mastocytoma. The ALVAC recombinant induced
      partial protection in both models. These results suggest that recombinant ALVAC
      and DNA might be interesting presentation platforms for p53 to be tested in
      clinical studies.

PMID- 9607033
TI  - Adjuvant activity of muramyl dipeptide derivatives to enhance immunogenicity of a
      hantavirus-inactivated vaccine.
AB  - The adjuvant effect of two lipophilic derivatives of muramyl dipeptide (MDP), B30
      MDP and MDP-Lys(L18), on the ability of an inactivated vaccine of B-1 virus (B-1
      vaccine) to induce immune response against Hantavirus causing hemorrhagic fever
      with renal syndrome (HFRS) was examined. When mice were immunized subcutaneously
      (s.c.) twice at 2-week intervals with B-1 vaccine admixed with or without 100
      micrograms mouse-1 of B30-MDP (B-1/B30-MDP) or MDP-Lys(L18) [B-1/MDP-Lys(L18)],
      mice immunized with B-1/B30-MDP as well as B-1/MDP-Lys(L18) showed significantly
      higher indirect fluorescent antibody (IFA) titers against HFRS virus than mice
      immunized with B-1 vaccine alone. Both mice treated with B-1/B30-MDP and B-1/MDP
      Lys(L18) also exhibited significantly higher neutralizing antibody titers against
      HFRS virus than mice immunized with B-1 vaccine alone during 3-9 weeks after the
      primary immunization. The evaluation of antibody-producing cells by enzyme-linked
      immunospot (ELISPOT) assay on week 4 revealed that both MDP derivatives enhanced
      the number of HFRS virus-specific IgG1 and IgM antibody-producing cells.
      Furthermore, mice treated with B-1/B30-MDP as well as B-1/MDP-Lys(L18) showed a
      higher level of Th-2 type cytokines, IL-4 and IL-6, in sera than mice treated
      with B-1 alone. In an in-vitro analysis of T lymphocyte proliferation to
      baculovirus-expressed recombinant nucleocapsid protein (rNP) of Hantaan 76-118
      strain, the splenocytes of mice treated with B-1/B30-MDP and B-1/MDP-Lys(L18) on
      week 4 showed a significantly higher proliferating activity than those treated
      with B-1 vaccine alone. In addition, when mice were immunized once with B-1
      vaccine admixed with or without B30-MDP and MDP-Lys(L18) and followed by
      intrafootpad (i.f.) injection of B-1 vaccine on day 7, mice immunized with B
      1/B30-MDP and B-1/MDP-Lys(L18) induced a higher delayed-type hypersensitivity
      (DTH) reaction than mice immunized with B-1 vaccine alone. These results suggest
      that B30-MDP and MDP-Lys(L18) are useful immunoadjuvants to enhance the ability
      of inactivated B-1 vaccine to induce a humoral and cellular response to HFRS
      virus.

PMID- 9607034
TI  - Temporal relationship modeling: DTP or DT immunizations and infantile spasms.
AB  - The time relationship between DTP immunization and infantile spasms (IS) onset
      was examined using three models--association, temporal shift, and no-effect--and
      the case/control data from the National Childhood Encephalopathy Study (NCES).
      Infantile spasms cases classified as being previously abnormal (e.g., tuberous
      sclerosis complex patients) showed a no-effect relationship, whereas those
      classified as previously normal suggested a fit to the temporal shift model, i.e.
      no increase in number of cases but a shortening of time to onset of seizure. No
      data fit the association model. Analyses for vaccine complications should examine
      for temporal changes (i.e. temporal shift) in addition to increased risks.

PMID- 9607035
TI  - Follow-up immunogenicity of an inactivated hepatitis A virus vaccine in healthy
      children: results after 5 years.
AB  - Long-term persistence of hepatitis A virus (HAV) serum antibody in vaccinated
      children has not been demonstrated in previous studies. To study the long-term
      immunogenicity to HAV vaccine, three doses of strain HM 175 HAV vaccine with 360
      enzyme-linked immunosorbent assay units were administered to 107 children, aged
      from 1.0 to 6.8 years, at 0, 1, and 6 months. The administration of one vaccine
      dose induced seropositivity (anti-HAV titer > or = 20 mIU ml-1) in 95% of all
      vaccinees at month 1. All subjects remained seropositive until month 6. The
      titers of HAV antibody remained above 20 mIU ml-1 in all subjects followed up to
      60 months. The geometric mean titer (GMT) reached its peak (3802 mIU ml-1) at
      month 7, i.e. 1 month after the booster dose, and then declined until the end of
      follow-up at month 60 (661 mIU ml-1). A trend of higher GMT in female subjects
      persisted up to month 60. The changes of the GMT over time were best described by
      the regression equation: log (GMT) = 3.26-0.08 x (age in years) (r = -0.95, P =
      0.014). According to this equation, the geometric mean concentration would reach
      20 mIU ml-1 at around 24.5 years after the beginning of vaccination. In
      conclusion, those who completed the recommended three-dose inactivated HAV
      vaccination series remained seroprotective for at least 5 years. Theoretically,
      such a vaccination program can provide a protective period of over 20 years in
      children. This paper may be the first to describe at least 5-year immunogenicity
      of inactivated HAV vaccination in healthy children.

PMID- 9607036
TI  - Placental transfer of maternal poliovirus antibodies in full-term and pre-term
      infants.
AB  - This study was designed to investigate the placental transfer of maternal
      poliovirus antibodies in full-term and pre-term infants. Two hundred healthy,
      Israeli born mothers and their infants, were enrolled immediately after birth.
      The study population comprised two groups: a full-term group of 150 mothers and
      their infants, and a pre-term group of 50 mothers and their infants (gestational
      age < 35 weeks). Maternal and umbilical cord blood samples were taken in all
      cases. Antibody titers against the three poliovirus serotypes and a polio virus
      type 1 strain that caused an outbreak in 1988 (epidemic strain 1) were measured
      by a microneutralization system. The proportion of individuals with protective
      titers against each of the poliovirus types tested was slightly lower in the
      infants compared with their mothers. When protection to all strains combined was
      tested, the difference between mothers and infants was significant (P < 0.05).
      Transplacental transfer to epidemic strain 1 was less effective--12% of the
      premature infants were not protected against it at birth. The geometric mean
      titers against poliovirus types 1, 3 and epidemic type 1 strain were
      significantly lower in the pre-term group than in the full-term group. In both
      the full-term and pre-term groups there were significant linear correlations
      between the maternal and neonatal antibody titers for each of the polio viruses
      tested. For all poliovirus types, the transfer of maternal antibodies to the full
      term infant was significantly higher than the transfer of maternal antibodies to
      the pre-term infant (P < 0.001). Owing to diminished transfer of maternal
      antibodies, pre-term infants are at greater risk of poliovirus infection.

PMID- 9607037
TI  - Immunisation with recombinant AMA-1 protects mice against infection with
      Plasmodium chabaudi.
AB  - The Plasmodium merozoite surface antigen apical membrane antigen-1 (AMA-1) has
      previously been shown to provide partial protection to Saimiri and rhesus monkeys
      immunised with recombinant Plasmodium fragile or parasite-derived Plasmodium
      knowlesi AMA-1, respectively. In the study reported here we have used the
      Plasmodium chabaudi/mouse model system to extend our pre-clinical assessment of
      an AMA-1 vaccine. We describe here the expression of the full-length Plasmodium
      chabaudi adami AMA-1 and the P. chabaudi adami AMA-1 ectodomain using both
      baculovirus and Escherichia coli. The ectodomain expressed in E. coli, which
      contained an N-terminal hexa-his tag, was purified by Ni-chelate chromatography
      and refolded in vitro in the presence of oxidised and reduced glutathione to
      generate intramolecular disulphide bonds. In a series of vaccine trials, in both
      inbred and outbred mice, highly significant protection was obtained by immunising
      with the refolded AMA-1 ectodomain. Protection was shown to correlate with
      antibody response and was dependent on intact disulphide bonds. Passive transfer
      of antibodies raised in rabbits against the refolded AMA-1 ectodomain was also
      protective. In view of this demonstration that E. coli expression of a soluble P.
      chabaudi AMA-1 domain can generate a vaccine that is effective in mice, we are
      pursuing a similar approach to generating a vaccine against P. falciparum for
      testing in human volunteers.

PMID- 9607038
TI  - Mutants of Escherichia coli heat-labile enterotoxin as an adjuvant for nasal
      influenza vaccine.
AB  - The effectiveness and safety of known mutants of Escherichia coli heat-labile
      enterotoxin (LT) as an adjuvant for nasal influenza vaccine were examined. Six
      mutants, called LT7K (Arg to Lys), LT61F (Ser to Phe), LT112K (Glu to Lys),
      LT118E (Gly to Glu), LT146E (Arg to Glu) and LT192G (Arg to Gly) were constructed
      by the replacement of one amino acid at one position of the A1 subunit to another
      using site-directed mutagenesis. All mutants were confirmed to be less toxic than
      wild-type LT when analyzed using Y-1 adrenal cells in vitro. When influenza
      vaccine was administered intranasally with LT7K and LT192G, BALB/c mice developed
      high levels of serum and local antibodies to the HA molecules. The adjuvant
      activity of these mutant LTs corresponded to that of wild-type LT when 1
      microgram of these mutant LTs (or wild-type LT) was coadministered with the
      vaccine. From the point of view of safety, LT7K was considered to be the most
      potent mucosal adjuvant and was examined in more detail. The adjuvant activity of
      the mutant was lowered more rapidly with a decrease in dose than was that of wild
      type LT. The low level of adjuvant of a relatively small amount of LT7K was
      heightened by adding LTB to the mutant LT. These results suggest that LT7K
      supplemented with LTB can be used as a less toxic, effective adjuvant for nasal
      influenza vaccine.

PMID- 9607039
TI  - Safety and immunogenicity of an oral inactivated enterotoxigenic Escherichia coli
      vaccine.
AB  - The safety and immunogenicity of two different lots, 001 and 003, of an oral
      inactivated enterotoxigenic Escherichia coli (ETEC) vaccine consisting of a
      mixture of formalin-killed whole bacteria expressing the most prevalent
      colonisation factor antigens, i.e. CFA/I, CFA/II and CFA/IV and recombinantly
      produced cholera B subunit (rCTB) have been evaluated in Swedish volunteers.
      Neither of the two vaccine preparations, containing different CFA/II-expressing
      strains but otherwise identical, gave rise to any significant side-effects.
      Mucosal immune responses, as reflected in antibody-secreting cell (ASC) responses
      in peripheral blood, were studied after two doses of vaccine and did not differ
      significantly for the two vaccine lots. Vaccination induced high levels of CTB
      specific IgA ASCs in 100% of the volunteers, and significant IgA ASC responses (9
      to 36-fold) were noted in 84% of them against CFA/I, in 87% against CFA/II
      subcomponents CS1-CS3 and in 91% against CFA/IV subfactors CS4 and/or CS5. The
      frequencies and magnitudes of CFA IgA ASC responses were similar when giving the
      vaccine with a 1 or 2 week interval. Results from serological analyses showed
      that the local IgA responses against CFAs are only infrequently associated with
      serum antibody titre rises.

PMID- 9607040
TI  - Vaccination as a means of control of foot-and-mouth disease in sub-saharan
      Africa.
AB  - The presence of foot-and-mouth disease (FMD) in a country is a major obstacle to
      the development of agriculture because of its adverse effects on livestock
      production and agricultural exports. The eradication of FMD in sub-saharan Africa
      by the implementation of slaughtering-out is impractical for various reasons, but
      vaccination with good quality FMD vaccines can help prevent losses in stock
      production and reduce the overall incidence of the disease. Oil based FMD
      vaccines have been used with success in South American countries and have
      logistic and immunological advantages which would make them useful in sub-saharan
      African countries. The wide intratypic variation of SAT strains prevalent in sub
      saharan Africa and their endemicity in African buffalo, presents a challenge to
      vaccine producers and requires constant epidemiological surveillance to ensure
      the relevance of vaccines to field conditions.

PMID- 9607041
TI  - An inactivated gE-negative marker vaccine and an experimental gD-subunit vaccine
      reduce the incidence of bovine herpesvirus 1 infections in the field.
AB  - An inactivated glycoprotein E-negative vaccine and an experimental glycoprotein D
      subunit vaccine against bovine herpesvirus 1 (V1) were examined for their
      effectiveness in a randomized, double-bline, placebo-controlled field trial
      comprising 130 dairy farms. The use of these marker vaccines enabled us to
      monitor the incidence of infections in vaccinated populations. The aims of this
      trial were to evaluate whether these vaccines: (1) reduce the proportion of
      outbreaks in dairy herds; and (2) reduced virus transmission within dairy herds
      and to what extent. Vaccination with either of the two vaccines significantly
      reduced the proportion of herds wherein an outbreak occurred as well as the virus
      transmission within herds, as compared to placebo-treated herds. The estimated
      number of secondary cases caused by one infectious animal, expressed as the
      reproduction ratio R, was for both vaccines significantly > 1. This indicates
      that when BHV1 is introduced into vaccinated herds, major outbreaks may still
      occur.

PMID- 9607042
TI  - Chimaeric HBV core particles carrying a defined segment of Puumala hantavirus
      nucleocapsid protein evoke protective immunity in an animal model.
AB  - Hantaviruses are rodent-born agents which are pathogenic in humans causing
      haemorrhagic fever with renal syndrome or hantavirus pulmonary syndrome. To
      induce a protective immunity against a European hantavirus (Puumala) we
      constructed chimaeric hepatitis B virus (HBV) core particles carrying defined
      fragments of the Puumala virus nucleocapsid protein. After immunisation of bank
      voles, the natural host of Puumala virus, with core particles possessing an
      insertion of the N-terminal part of Puumala virus nucleocapsid protein, four of
      five animals were protected against subsequent virus challenge. The results show
      that the major protective region of the nucleocapsid protein is located between
      amino acids 1 and 45 and that chimaeric HBV core-like particles are useful
      carriers of foreign protective epitopes.

PMID- 9607043
TI  - Wild type mumps viruses circulating in China establish a new genotype.
AB  - By analysing the nucleotide sequence of the SH genes of five mumps virus strains
      derived from the clinical specimens collected during the 1995/96 mumps epidemic
      in China a new genotype has been established. The circulating viruses showed
      divergence ranging from 0.8-4.5% at the nucleotide level and 3.5-12.3% at the
      amino acid level. In addition, a more rational approach has been taken in
      proposing genotype groupings to MuV strains.

PMID- 9607044
TI  - Induction of mucosal and systemic immune responses by intranasal immunization
      using recombinant cholera toxin B subunit as an adjuvant.
AB  - Intranasal (i.n.) immunization with Streptococcus mutans surface protein AgI/II
      mixed with cholera toxin B subunit (CTB) containing a trace amount of cholera
      toxin (CT) induces strong immune responses in mucosal and systemic sites, but
      whether pure CTB alone has an adjuvant effect has been questioned. To determine
      the adjuvant effect of recombinant (r) CTB, mice were immunized with 10
      micrograms of AgI/II either mixed with or conjugated to 5 micrograms of rCTB, and
      antibody responses in saliva, nasal wash, gut wash, vaginal wash, and serum were
      assayed by ELISA. The results showed that AgI/II either mixed with or conjugated
      to rCTB could induce both mucosal IgA and systemic IgG antibodies to higher
      levels than in mice similarly immunized with AgI/II alone. Some responses,
      especially serum IgG antibodies, were enhanced by adding 5 micrograms CT to the
      immunogen, whereas overall mice immunized with AgI/II mixed with CTB contaminated
      with CT tended to generate the strongest mucosal IgA and serum IgG responses to
      AgI/II. However, rCTB used as an adjuvant induced lower antibody responses
      against itself than CTB intentionally or inadvertently mixed with CT. These
      results show that rCTB can serve as an adjuvant for protein immunogens
      administered by the i.n. route.

PMID- 9607045
TI  - Durable immunity and immunologic memory to a parasite antigen induced by somatic
      transgene immunization.
AB  - Somatic transgene immunization (STI) is an alternative approach to immunization
      mediated by inoculation of plasmid DNA. In the experiments presented here we show
      that inoculation of plasmid DNA carrying an immunoglobulin heavy chain gene under
      the control of tissue-specific regulatory elements, leads to immunity and
      persistent immunologic memory against a peptide epitope encoded in the third
      complementarity-determining region. The epitope consists in three repeats of the
      tetrapeptide Asn-Ala-Asn-Pro (NANP) and is the immunodominant B cell epitope
      expressed at the surface of Plasmodium falciparum malaria parasite. When
      inoculated directly in the spleen the plasmid DNA initiated a specific anti-NANP
      response which lasted for 2 years. During the initial phase of priming the anti
      NANP response was higher than that induced by immunization with recombinant
      protein in immunologic adjuvants. The establishment of immunologic memory was
      probed by single booster injection at various times after priming. We found that
      STI induces persistent immunologic memory up to 2 years. The immunologic
      characteristics of this new model are examined with respect to the requirement
      for the induction of B cell memory.

PMID- 9607046
TI  - Safety and characterization of the immune response engendered by two combined
      measles, mumps and rubella vaccines.
AB  - We performed a randomized trial to compare the safety and immunogenicity of two
      combined measles, mumps and rubella vaccines in healthy children 14-24 months of
      age. Triviraten Berna Vaccine (Swiss Serum and Vaccine Institute), contains the
      Edmonston Zagreb 19 strain of measles virus, the Rubini mumps virus strain and
      the Wistar RA 27/3 rubella strain while MMR-Vax (Merck, Sharp & Dohme, West
      Point, PA) contains the Enders attenuated Edmonston measles strain, the Jeryl
      Lynn mumps strain and the Wistar RA 27/3 rubella strain. Immunization with
      Triviraten Berna was associated with a significantly lower incidence of swelling
      and redness at the injection site in addition to a reduced rate of fever compared
      with MMR-Vax. Seroconversion rates for the measles and rubella vaccine components
      were comparable in all tests used. However, seroconversion for the mumps vaccine
      component was test-dependent. Using an ELISA, the seroconversion rate following
      immunization with MMR-Vax was significantly (P < 0.01) higher than for Triviraten
      Berna. In contrast, nearly identical rates were obtained using an indirect
      immunofluorescence test. Both vaccines were equally effective at engendering
      antibodies capable of neutralizing wild type mumps virus. Geometric mean ELISA
      antibody titers against measles and mumps virus were higher following
      immunization with MMR-Vax while that for rubella was higher after immunization
      with Triviraten Berna. A small number (N = 13) of adolescents immunized either
      with MMR-Vax or Triviraten Berna were reimmunized with Triviraten Berna and
      various humoral and cellular response parameters to the measles and mumps vaccine
      components analyzed. While few subjects mounted a humoral antibody response to
      measles, most likely due to elevated baseline titers, there was a marked
      lymphoproliferative response. Anti-mumps virus ELISA antibody titers were higher
      both at baseline and after reimmunization in subjects who received MMR-Vax for
      primary immunization. However, there was no difference in either neutralizing
      titer or proliferative response in subjects primed with MMR-Vax or Triviraten
      Berna either before or after reimmunization.

PMID- 9607047
TI  - Immunogenicity of Plasmodium falciparum circumsporozoite protein multiple antigen
      peptide vaccine formulated with different adjuvants.
AB  - Only low antibody levels were obtained from vaccinating human volunteers with
      single-chain peptide from the Plasmodium falciparum circumsporozoite protein
      (PfCSP). This resulted in modest protection against sporozoite challenge. In
      addition, HLA restriction limits the probability of synthesis of a vaccine
      effective for a diverse population. We report immunization studies with a
      multiple antigen peptide (MAP) system consisting of multiple copies of a B-cell
      epitope from the central repeat region of the PfCSP in combination with a
      universal T-cell epitope, the P2P30 portion of tetanus toxin. This
      MAP4(NANP)6P2P30 vaccine was highly immunogenic in four different strains of mice
      when used with various safe and nontoxic adjuvants. When this MAP vaccine was
      encapsulated in liposomes with lipid A and adsorbed to aluminium hydroxide and
      given three times at 4-week intervals, the resultant antibody prevented 100% of
      sporozoites from invading and developing into liver stage infection. This high
      degree of immunogenicity of MAP4(NANP)6P2P30 vaccine formulated in liposomes,
      lipid A and aluminum hydroxide provides the foundation for consideration of human
      trials with this formulation.

PMID- 9607048
TI  - Circulating antibody secreting cell response to parenteral pneumococcal vaccines
      as an indicator of a salivary IgA antibody response.
AB  - This study assessed the mucosal immune response in healthy adult volunteers
      immunized parenterally with either pneumococcal polysaccharide (N = 8) or
      pneumococcal polysaccharide-protein conjugate (N = 10) vaccine with an aim to
      evaluate the relevance of antibody secreting cell (ASC) response after parenteral
      vaccination. An ASC response to the four types of capsular polysaccharide tested
      was observed in all vaccinees 7-9 days after immunization. IgA was the
      predominant class in the ASC response, and IgG the next common, with very few IgM
      ASCs. The IgA/IgG ratio in the ASC response was higher after immunization with
      the polysaccharide than the conjugate vaccine. Antibodies of the IgA class were
      frequently seen in the saliva already before immunization; especially to
      serotypes 14 and 19F. A twofold increase of the type specific secretory IgA
      antibodies in saliva was found in eight of the 16 instances in which the specific
      IgA ASC response was > 100 ASC per 10(6) cells and in only one of the 52
      instances with fewer ASCs. We conclude that the ASC response in the peripheral
      blood is a useful parameter of the antibody response to pneumococcal vaccines and
      a good indicator of a secretory IgA response in the saliva.

PMID- 9607049
TI  - Predictors of adverse events after the administration of acellular and whole-cell
      diphtheria-tetanus-pertussis vaccines.
AB  - Recurrence of adverse events, the effect of site of injection, and concurrent
      administration of oral polio vaccine (OPV) and hepatitis B vaccine (HBV) on
      reactogenicity were assessed in recipients of two acellular pertussis vaccines
      given in combination with diphtheria and tetanus toxoids (DTaP), one whole-cell
      DTP vaccine (DTPwc) and one DT vaccine during a double blind, randomized,
      controlled clinical trial. Local and systemic side reactions were more likely to
      recur after the administration of DTaP and DT compared with DTPwc. In all vaccine
      groups, injection in the buttock was associated with a lower rate of common
      adverse events compared with injection in the thigh, while simultaneous
      administration of OPV and/or HBV did not increase the risk of onset of side
      reactions.

PMID- 9607050
TI  - Immunity to mumps before and after MMR vaccination at 12 years of age in the
      first generation offered the two-dose immunization programme.
AB  - Sweden was the first country in the world to introduce a two-dose programme of
      vaccination against measles, mumps and rubella with a combined vaccine (MMR). It
      was commenced in 1982 and the vaccination was carried out at the ages of 18
      months and 12 years. In 1992-93 the first age-group vaccinated at 18 months
      reached the age of 12 and accordingly received a second dose of MMR. A total of
      382 children participated in the present study. Sero-immunity against mumps was
      studied by testing neutralizing antibodies using serial dilutions inoculated into
      cell cultures before and after the 12-year vaccination. Of the 229 children
      earlier vaccinated (group A), 27% lacked demonstrable antibodies before the
      booster. Of those without documented vaccination records (group B), 56% were
      seronegative before vaccination. After vaccination, 93% of group A and 86% of
      group B were seropositive (titre > or = 2). In the seronegative children, whether
      vaccinated earlier or not, the seroconversion was ca 75%. Previously unvaccinated
      children positive before vaccination and thus likely to be naturally immune had a
      higher mean-titre both before and after vaccination than the seropositive
      children earlier vaccinated. So far, the two-dose programme has proceeded as
      expected.

PMID- 9607051
TI  - Major adverse reactions to yeast-derived hepatitis B vaccines--a review.
AB  - Yeast-derived recombinant DNA hepatitis B vaccines usage became widely accepted
      since the early 1990s. Severe adverse events have been reported infrequently in
      adults and rarely in infants and children given hepatitis B vaccine in the ten
      years which have passed since the introduction of the vaccine. Some of the data
      were summarized in previous review articles. Our review of the literature
      revealed reports of serious adverse reactions which included immediate reactions
      (anaphylaxis and urticaria) as well as delayed reactions, including skin,
      rheumatic, vasculitic (including Systemic Lupus Erythematosus and
      glumerulonephritis), hematologic, ophthalmologic and neurologic reactions. These
      cases were summarized and a pathogenetic mechanism is offered.

PMID- 9607052
TI  - Host factors affecting the homologous and heterologous immune response of cattle
      to FMDV: genetic background, age, virus strains and route of administration.
AB  - Sixty bulls were tested for antibodies to the heterologous serotype C1 of FMDV
      following repeatable vaccinations with a commercial trivalent vaccine (O1, A22,
      Asia1). Six (10%) bulls were found to possess rather high levels of heterologous
      neutralizing antibodies which showed accumulative trend with age. Two high
      positive and two negative bulls for the heterologous serotype C1 were selected
      for progeny test involving ten daughters of each bull. The four bulls, either
      positive or negative for the heterologous serotype C1, showed significant
      phenotypic correlation between their heterologous and homologous titers (O1, A22,
      Asia1). This correlation between heterologous and homologous antibody titers was
      not found in the daughters of these bulls. However, two of ten daughters of one
      positive bull, to C1 showed individual high titers (> or = 1.5). The intradermal
      (ID) as compared to subcutaneous (SC) route of administration resulted in higher
      rate of responders to both heterologous serotypes C1 and SAT1. The heterologous
      immune response to FMDV in Israeli-Friesian cattle was found to be related to the
      age of the host, multiplicity of vaccinations, route of vaccination, kind and
      numbers of the antigens used in the vaccine. The homologous immune response is
      also controlled by genetic factors.

PMID- 9607053
TI  - Adjuvant/carrier activity of inactivated tick-borne encephalitis virus.
AB  - Virus-like or virus-derived particles have been reported to increase the
      immunogenicity of foreign antigens. In this study formaldehyde-inactivated tick
      borne encephalitis virus (TBEV), a potent immunogen in humans, was tested for
      possible adjuvant/carrier function. The results of our study revealed that
      substantial antibody titers against very low doses of tetanus toxoid could be
      obtained when mice were immunized with the antigen covalently coupled to TBEV
      (using N-succinimidyl-3-(2-pyridyldithio)propionate, a heterobifunctional,
      cleavable crosslinker containing a disulfide bridge). In contrast, only moderate
      anti-tetanus toxoid titers were induced by immunizations with a simple mixture of
      low dose tetanus toxoid and TBEV or when the disulfide bridge of the crosslinker
      used to couple tetanus toxoid to TBEV was cleaved prior to immunization. The
      antibody response to TBEV, on the other hand, was not influenced by its linkage
      to tetanus toxoid. Comparable anti-TBEV titers were obtained following
      immunization of the animals with either the TBEV-tetanus toxoid conjugate or the
      mixture of tetanus toxoid and TBEV. Prior application of a TBEV vaccine did not
      change the antibody response against tetanus toxoid and thus carrier-induced
      epitopic suppression could be ruled out. The abovementioned adjuvant/carrier
      properties of TBEV might make it a suitable candidate for use in bi- or
      multivalent vaccines containing weak immunogens.

PMID- 9607054
TI  - Controlled release microparticles as a single dose diphtheria toxoid vaccine:
      immunogenicity in small animal models.
AB  - Diphtheria toxoid (DT) was encapsulated in microparticles prepared from
      polylactide-co-glycolide (PLG) polymers using a solvent evaporation technique.
      Combinations of small and large sized microparticles with controlled release
      characteristics were used to immunize Sprague Dawley rats and the antibody
      responses were monitored for one year. For comparison, control groups of rats
      were immunized at 0, 1 and 2 months with DT adsorbed to alum. The antibody
      responses generated by the microparticles were comparable to the alum immunized
      control groups from 32 weeks. Microparticles with a single entrapped antigen (DT)
      induced better antibody responses than microparticles with two antigens entrapped
      simultaneously (DT + TT). Microparticles prepared from a single polymer were less
      effective for long term antibody induction than a combination of microparticles
      prepared from three different polymers. A combination vaccine consisting of
      antigen absorbed to alum and also entrapped in microparticles gave the best
      response. In an inhibition assay designed to determine the relative binding of
      antisera to the antigen, the sera from the microparticle and the alum immunized
      animals showed comparable binding. An intradermal challenge study was performed
      in rabbits, which showed similar levels for the alum and the microparticle
      immunized animals at 4, 12 and 32 weeks after immunization.

PMID- 9607055
TI  - Polyvalent vaccination against hepatitis B surface and core antigen using a
      dicistronic expression plasmid.
AB  - Genes encoding the small (S) surface antigen (HBsAg) or the core (C) antigen
      (HBcAg) of hepatitis B virus (HBV) were cloned into the monocistronic expression
      vectors pCMV-1 or pCMV-2 under HCMV-IE promoter control. Coding fragments of
      these vectors were fused to generate a dicistronic expression construct pCMV/C-S
      in which the antigens HBcAg and HBsAg are coexpressed. Transient in vitro
      transfection studies demonstrated that HBcAg and HBsAg are coexpressed from this
      construct. Vaccination of mice of different H-2 haplotypes with mono- or
      dicistronic expression plasmids induced humoral and cellular immune responses to
      HBsAg and the HBcAg. In particular, intramuscular injection of 'naked'
      dicistronic plasmid DNA into mice elicited polyvalent humoral and cytotoxic T
      lymphocyte responses to HBsAg and HBcAg. The studies demonstrate that dicistronic
      expression plasmids are a novel way to construct a polyvalent vaccine against HBV
      that comprises HBsAg and HBcAg as immunogens.

PMID- 9607056
TI  - Antibody titers eight months after three doses of a five-valent pneumococcal
      conjugate vaccine in HIV and non-HIV-infected children less than two years of
      age.
AB  - The objective of this study was to examine vaccine type-specific antibody titers
      eight months after a five-valent pneumococcal conjugate vaccine (PCV) in human
      immunodeficiency virus (HIV) and non-HIV-infected children under two years of
      age. Sixteen HIV-infected and 14 non-HIV-infected children under two years of
      age, and of similar age, race and sex distribution, received three doses
      (separated by two months each) of a five-valent oligosaccharide PCV (types 6B,
      14, 18C, 19F, and 23F separately coupled to diphtheria CRM197). An additional 11
      non-HIV-infected children, of similar demographic distribution to the PCV groups,
      received three doses of saline placebo. sera were collected just prior to, and at
      one and eight months after the three study drug doses. Serum vaccine type
      specific pneumococcal IgG antibodies were measured by enzyme-linked
      immunoabsorbant assay (ELISA). There was an impressive rise in antibody titers
      pre- to one month post-third PCV in both the HIV (58-970-fold) and non-HIV
      infected (19-553-fold) children. There was a rapid and similar drop in antibody
      titers eight months after the PCV series for both HIV (range 69-87% drop) and non
      HIV-infected (range 57-79% drop) subjects respectively. However, 46% of the
      antibody titers from HIV-infected children and 62% of the titers from non-HIV
      infected children were still > 1.0 microgram ml-1 compared to placebo recipients
      for whom only 5% of the titers were > 1.0 microgram ml-1 (p < 0.05). At the eight
      month post-PCV series blood draw, there were no significant differences in the
      GMTs, the percent drop in titers, or proportion of titers > 1.0 microgram ml-1
      between the five HIV-infected children who had advanced (CDC class: N3, A3, B2-3,
      C1-3) compared to the 11 children with mild (CDC class: N1-2, A1-2, B1) HIV
      disease at the time of their first PCV dose. Eight months after the PCV series,
      the proportion of titers (combined all five serotypes) > 1.0 microgram ml-1 was
      slightly, but significantly, lower for HIV-infected subjects (46%) compared to
      non-HIV-infected subjects (62%) (p < 0.05). These data are helpful in describing
      the kinetics of antibody responses to pneumococcal conjugate vaccines in both HIV
      and non-HIV-infected young children.

PMID- 9607057
TI  - Field studies and cost-effectiveness analysis of vaccination with Gavac against
      the cattle tick Boophilus microplus.
AB  - The control of tick infestations and the transmission of tick-borne diseases
      remains a challenge for the cattle industry in tropical and subtropical areas of
      the world. Traditional control methods have been only partially successful and
      the parasites continue to result in significant losses for the cattle industry.
      Recently, vaccines containing the recombinant Boophilus microplus gut antigen
      Bm86 have been developed. These vaccines have been shown to control tick
      infestations in the field. However, extensive field studies investigating the
      efficacy and cost-effectiveness of vaccination have not been reported and are
      needed to appraise the effect of this new approach for tick control. Here is
      reported the results of the application of Gavac in a field trial including more
      than 260,000 animals in Cuba. In this study the correlation between the antibody
      response to vaccination and the effect on ticks fertility is determined.
      Physiological status of the animals was found to affect the primary response to
      vaccination but not the antibody titers after revaccination. A cost-effectiveness
      analysis showed a 60% reduction in the number acaricide treatments, together with
      the control of tick infestations and transmission of babesiosis, which resulted
      in savings of $23.4 animal-1 year-1. These results clearly demonstrate the
      advantage of vaccination and support the application of Gavac for tick control.

PMID- 9607058
TI  - Effect of particulation on the immunogenic and protective properties of the
      recombinant Bm86 antigen expressed in Pichia pastoris.
AB  - The recombinant Bm86 tick antigen expressed in Pichia pastoris is obtained in a
      highly particulated form, as a distinguish feature of this expression system.
      This particulated protein, the active principle of the recombinant vaccine Gavac
      against the cattle tick, have shown high immunogenic and protective properties,
      probably associated with its own characteristics. To evaluate the effects of
      particulation on the properties of Bm86, three groups of calves were immunized
      with particulated or non-particulated recombinant Bm86 and the anti-Bm86 antibody
      response determined. Animals were challenged with a controlled tick infestation
      and the protective capacities of both proteins assessed. Humoral immune response
      and protection in cattle vaccinated with the particulated antigen were higher.
      These experiments suggested that particulation of the Bm86 expressed in P.
      pastoris is an important feature for the protective properties of the antigen in
      vaccine preparations.

PMID- 9607059
TI  - Safety and immunogenicity of live, attenuated human rotavirus vaccine 89-12.
AB  - The safety and immunogenicity of an orally administered live human rotavirus
      vaccine candidate (89-12), attenuated by 33 passages in monkey kidney cells, were
      evaluated in placebo-controlled trials in adults, children and infants. This
      strain was selected because natural infections with 89-12-like rotaviruses
      provided 100% protection over two years. The initial evaluations in adults,
      seropositive children and nine infants indicated that the vaccine was safe. Two
      doses of vaccine (10(5) p.f.u. dose-1) or placebo were then given to 42 infants,
      aged from 6 to 26 weeks. No significant difference in side effects was seen.
      Seroconversion was demonstrated in 19 of 20 previously uninfected vaccine
      recipients, but > or = 4-fold rises in 89-12 neutralizing antibody titers were
      detected in only seven subjects. Intestinal IgA responses were detected in 15
      subjects. This attenuated human rotavirus was safe and immunogenic and should be
      further evaluated as a vaccine candidate.

PMID- 9607061
TI  - Intradermal DNA immunization of mice against influenza A virus using the novel
      PowderJect system.
AB  - The PowderJect system, a device that uses compressed helium gas to accelerate
      microscopic particles into the skin, was used as a delivery system for DNA
      vaccines to elicit a virus-specific cytotoxic T cell response (CTL) in mice.
      Transient expression of beta-galactosidase (beta-Gal) was observed in the
      epidermis when gold particles coated with beta-Gal expression plasmid were
      delivered to mouse skin with the device. When DNA encoding the nucleoprotein gene
      (NP) of influenza A virus was used to coat gold particles, a strong and specific
      anti-NP CTL response was elicited by immunizations with nanogram amounts of the
      NP DNA vector. This study shows the potential for application of the PowderJect
      system to intradermal delivery of DNA in order to elicit an immune response.

PMID- 9607060
TI  - Oral passive immunization against experimental salmonellosis in mice using
      chicken egg yolk antibodies specific for Salmonella enteritidis and S.
      typhimurium.
AB  - The efficacy of chicken egg yolk homotypic antibodies specific for outer membrane
      proteins (OMP), lipopolysaccharide (LPS) or flagella (Fla) in controlling
      experimental salmonellosis in mice was investigated. Mice challenged orally with
      2 x 10(9) c.f.u. of Salmonella enteritidis or 2 x 10(7) c.f.u. of S. typhimurium
      were orally treated with 0.2 ml anti-OMP, -LPS or -Fla yolk antibody three times
      a day for three consecutive days. In mice challenged with S. enteritidis,
      antibody treatment resulted in a survival rate of 80%, 47% and 60% using OMP, LPS
      or Fla specific antibodies respectively, in contrast to only 20% in control mice.
      In the S. typhimurium trial, survival rate was 40%, 30% and 20% using OMP, LPS or
      Fla specific antibodies respectively in contrast to 0% in control mice. In vitro
      adhesion of S. enteritidis and S. typhimurium to HeLa cells was significantly
      reduced by anti-OMP, -LPS, and -Fla homotypic antibodies. Results suggest that
      egg yolk antibodies specific for Salmonella OMP, LPS, and Fla may protect mice
      from experimental salmonellosis when passively administered orally. Of these
      antibodies, anti-OMP exhibited the highest level of protection in vivo and in
      vitro.

PMID- 9607063
TI  - Immune response to influenza vaccination in institutionalized elderly: effect on
      different T-cell subsets.
AB  - Humoral and cellular immunological responses to influenza vaccination were
      measured in volunteers in a long-term care facility. All participants were
      vaccinated with the commercially available 1994-95 trivalent influenza vaccine
      and blood samples were collected before and 6 and 12 weeks after vaccination.
      Cytokine and granzyme B in peripheral blood mononuclear cell (PBMC) cultures
      after virus stimulation, and serum antibody titres were measured for each of
      these time points. In general, the measures of the immunological response to
      vaccination were low and variably significant. The major finding was the
      difference with respect to post-vaccination measures for the two strains of
      influenza A contained in the vaccine. Geometric mean antibody titres were
      significantly higher for A/Texas/36/91 at all time points in the study when
      compared to A/Shangdong/09/93. There was a corresponding rise for interleukin-10
      (IL-10) to the A/Texas/36/91 strain while no increase in IL-10 was observed in
      A/Shangdong/09/93-stimulated cultures after vaccination. In contrast, granzyme B
      rose after vaccination only in cultures stimulated with A/Shangdong/09/93.
      Interferon-gamma levels were also significantly higher in these PBMC cultures.
      There was a poor interleukin-2 (IL-2) response to both strains of influenza A.
      These data suggest that different strains or subtypes of influenza A may
      preferentially enhance T-helper type 1 versus type 2 responses through
      vaccination in institutionalized seniors.

PMID- 9607062
TI  - Revaccination against hepatitis B virus of non-responding and low-responding
      infants immunised at birth. A parallel evaluation of rubella and tetanus vaccine.
AB  - The aim of the present study was to identify the true extent of the non
      responsiveness in infants born from HBsAg-negative mothers, vaccinated against
      Hepatitis B Virus (HBV) at birth. Sixty-four non- and low-responding infants,
      selected from an initial cohort of 2009, were given two additional doses of
      recombinant HBV vaccine between the tenth and the twelfth month of age. A
      parallel evaluation was conducted on the response to anti-rubella and anti
      tetanus vaccine. Only two infants remained non-responders, whereas 68% of the non
      responders and 94% of the low responders after the primary vaccination schedule
      developed antibody titres over 100 mIU ml-1. No significant relationship between
      the specific antibody level against HBV and against rubella or tetanus 1 month
      after vaccination was observed.

PMID- 9607064
TI  - The efficacy of a whole cell pertussis vaccine and fimbriae against Bordetella
      pertussis and Bordetella parapertussis infections in a respiratory mouse model.
AB  - Due to local and systemic side-effects, the currently used, highly effective,
      whole-cell pertussis vaccines (WCVs) will be replaced by acellular vaccines
      (ACVs) in some countries. These ACVs contain detoxified pertussis toxin, either
      alone or in combination with the filamentous haemagglutinin, pertactin and
      fimbriae. Ongoing clinical trials show that ACVs are clearly less reactogenic
      than WCVs and that ACVs comprised of three to five proteins are highly
      efficacious in inducing protection against Bordetella pertussis infections. An
      important unresolved question is, what the effect will be of the switch from WCVs
      to ACVs on the incidence of Bordetella parapertussis infections, the second
      causative agent of pertussis. A comparison of the efficacy of WCVs and ACVs
      against B. parapertussis infection is required to answer this question. We show
      that the Dutch WCV, although prepared from B. pertussis strains, protects against
      B. parapertussis infection in a murine respiratory model, although less
      efficiently than against B. pertussis infection. It was shown previously that the
      ACV components pertussis toxin, FHA and pertactin did not protect against B.
      parapertussis infection in a murine respiratory model. We have investigated the
      efficacy of two other ACV components, B. pertussis serotype-2 and -3 fimbriae
      against B. parapertussis infection in the murine model. The B. pertussis fimbriae
      protected mice against B. parapertussis infection although less efficiently than
      against B. pertussis infection. This result indicates that B. pertussis and B.
      parapertussis fimbriae are antigenically distinct. B. pertussis fimbriae were
      found to be as efficacious as the WCV against B. pertussis infection. Our results
      are discussed in the light of the switch from WCVs to ACVs.

PMID- 9607065
TI  - DNA-based immunization for exploring the enlargement of immunological cross
      reactivity against the lyssaviruses.
AB  - DNA-based immunization was used for studying the cross-reactivity of lyssavirus
      neutralizing antibodies and for exploring the induction of a wider range of
      protection against lyssaviruses. In order to immunize mice with homogeneous and
      chimeric genes of glycoproteins (G) from two divergent lyssaviruses, we used for
      the first time a new plasmid (pCI-neo) known to be a highly efficient vector for
      in vitro expression. The homogeneous plasmids pGPV and pGMok encoded the Pasteur
      virus (PV: genotype 1-GT-) and Mokola virus (Mok: GT 3) G, respectively. The
      chimeric pGMokPV encoded the NH2 part of GMok and the COOH part of GPV. These
      plasmids elicited full protection against intracerebral challenges with various
      lyssaviruses and a range of antigen-specific and non-specific immune responses.
      Virus neutralizing antibody (VNAb) levels were dose dependent and a single
      intramuscular (i.m.) injection of plasmids was sufficient to induce continuous
      high levels of VNAb. Production of antigen-specific T helper (Th), cytotoxic T
      cells (Tc) and non-specific natural killer cells was observed. Cross-reactivity
      studies showed that VNAb are obtained by immunizing with: (i) pGPV against GT 1
      (classical rabies), GT 4 (Duvenhage: Duv), GT 5 (European Bat Lyssavirus: EBL-1)
      and GT 6 (European Bat Lyssavirus: EBL-2); (ii) pGMok against GT 2 (Lagos Bat:
      LB) and GT 3 (Mokola: Mok); (iii) pGMokPV against all GTs except GT 4 which is
      weakly neutralized. Therefore, the DNA-based immunization with the chimeric
      pGMokPV, could be very interesting to enlarge protection to all the lyssaviruses.
      According to the cross-reactivity of VNAb induced by the G genes, the lyssavirus
      GTs could be classified into two groups: the first including GT 1, 4, 5 and 6;
      the second including GT 2 and 3.

PMID- 9607066
TI  - DNA multi-CTL epitope vaccines for HIV and Plasmodium falciparum: immunogenicity
      in mice.
AB  - The potential of building multi-cytotoxic T lymphocyte (CTL) epitope antigens in
      combination with the nucleic acid immunization technology is explored for
      development of acquired immunodeficiency syndrome (AIDS) and malaria vaccines. A
      novel minimal vector pTH for direct gene transfer was constructed for efficient
      expression of vaccine antigens and used as a vehicle for human immunodeficiency
      virus (HIV)- and Plasmodium falciparum-derived polyepitope genes. Two murine
      epitopes were included into these constructs to allow for testing of vaccine
      immunogenicity in small animals. The results showed that a single DNA injection
      generated CTL responses in all 15 vaccinated mice. The elicited CTL precursor
      frequencies were estimated in an interferon-gamma (IFN-gamma)-based ELISPOT assay
      and found to be an average of 300 (range 4-1346) peptide-responding cells per
      10(6) splenocytes.

PMID- 9607067
TI  - [Endoscopic ultrasonography in the diagnosis of submucosal tumors of the upper
      digestive tract].
AB  - Endoscopic Ultrasonography (EUS) was performed in 520 patients. In 78 subjects,
      it was indicated because of endoscopic suspicion of submucosal tumors (SMT),
      later confirmed in 67 patients. Thirty seven patients were symptomatic; in 22
      patients the finding was incidental and in 7 the indication was unknown.
      According to the ecogenic pattern of the lesions found and the layer of the tumor
      origin the following were diagnosed: 14 leiomyomas, 1 lipoma, 3 granular cell
      tumors and 2 without precise diagnosis in the esophagus. Thirty leiomyomas, 6
      leiomyosarcomas, 4 lipomas, 4 ectopic pancreas and 2 without precise diagnosis in
      the stomach. One leiomyoma in the duodenum. From the 11 SMT initially suspected
      by endoscopy which showed an integrity of the wall there were 10 extrinsic
      compressions and 1 without pathological findings. To date, surgery was performed
      on 22 patients with SMT complicated with ulcer and/or hemorrhage and on those
      larger than 3 cm with an ecogenic pattern, suspected of malignancy. Thirteen
      gastric leiomyomas, 2 gastric lipomas and 1 ectopic pancreas, with a 100%
      correlation in the postresection histological studies, 2 Abricosoff tumors of the
      esophagus, 2 leiomyosarcomas with 100% correlation and a giant lipoma of the
      esophagus which resulted in a liposarcoma, and 1 leiomyoma which resulted in a
      leiomyosarcoma were found. According to these results 90% diagnostic specificity
      and 100% sensitivity make this imaging technique the ideal method to evaluate
      these lesions and one of the main indications together with the staging of
      gastrointestinal tumors.

PMID- 9607068
TI  - [Post-treatment assessment of Helicobacter pylori eradication, by polymerase
      chain reaction in gastric biopsies].
AB  - BACKGROUND: The pre-treatment detection of H.p. in the stomach of patients is
      easily achieved with routine methods. Conversely, with conventional methods, it
      is difficult to detect the presence of H.p. after treatment. OBJECTIVE: To
      estimate the actual percentage of successfully treated patients by using a more
      sensitive and specific technique (PCR) in the same biopsies where standard
      methods were negative for H.p. MATERIALS AND METHODS: We selected 97 treated
      patients (31 Gastric Ulcers/66 Duodenal Ulcers, 62 male/35 female, age: 49 +/- 14
      years), in whom success of treatment was defined by histological means and CLO
      Test. In the same gastric biopsies H.p-DNA PCR was performed. Different
      therapeutic schemes were utilized, but all included Proton Pump Inhibitors + ATB.
      Eight weeks after the end of the treatment, without medication, the patients were
      controlled as follows: 5 biopsies per patient, 2 of antrum, 2 of corpus (in
      different zones) and 1 for CLO Test. H.p. eradication was defined on histological
      grounds (gastric biopsy histology: 10% formaldehide buffer fixation, paraffin
      inclusion, Giemsa, HE staining and inmunohistochemistry), CLO Test (Delta West
      Pty. Ltd. Bentley, Australia) and by the absence of H.p.-DNA by PCR
      (amplification of a 296 bp of the species-specific antigen of H.p. and
      visualization of the amplified product in agarose gel with Ethidium Bromide and
      UV light). RESULTS: [table: see text] CONCLUSIONS: The higher sensitivity of PCR
      (10(3) fold more than conventional methods) allowed us in this group of patients
      to detect 13% of false eradication. It would be necessary to follow up this group
      of patients in order to know whether they develop or not clinical symptoms and/or
      histological evidence of disease. If such a case PCR could become an important
      tool for treatment evaluation.

PMID- 9607069
TI  - [Neoadjuvant therapy in advanced carcinoma of the esophagus: prognostic value of
      the histopathological response].
AB  - The purpose of this study was to determine the prognostic value of the
      histopathological response to preoperative radio-chemotherapy in patients with
      locally advanced oesophageal cancer. Among the 57 patients included in this open
      prospective study, the disease-free cervical of 48 patients who underwent an
      oesophagectomy was correlated with the histopathological finding. The 5-years
      probability of disease-free cervical was 22.1%. Cervical of the patients whose
      tumor had been downstaged to no residual carcinoma or superficial oesophageal
      carcinoma was significantly shorter than that of patients with superficial
      oesophageal carcinoma at presentation treated during the same period (35% vs
      57%). Univariate analysis could identify 4 prognostic variables after induction
      therapy: adenocarcinoma, macroscopic, residual tumor, invaded oesophageal stump,
      and lymph node involvement. After multivariate analysis according to the Cox
      model, the remaining independent predictors of recurrence were: adenocarcinoma,
      invaded oesophageal stump, and lymph node involvement.

PMID- 9607070
TI  - [Functional characteristics of the Langerhans islets in type I gastric
      heterotopic pancreas].
AB  - In a retrospective five years study of gastric wall tumors, we selected the type
      1 heterotopic pancreas. The assessment of fibrosis and inflammatory infiltrate
      were performed. Also the immunohistochemical evaluation with monoclonal
      antibodies for insulin, glucagon, p substance, somatostatin, gastrin and
      antichimotrypsin. None of the case showed remarkable fibrosis or inflammatory
      infiltrate. All the Langerhans's islets stained positive for 2 or 3 hormones,
      gastrin and antichimotrypsin were always negative. These findings are comparable
      with others previously reported, but no cases of evaluation of islet's gastrin
      exist in the literature reviewed.

PMID- 9607071
TI  - [Human papillomavirus, neonatal giant cell hepatitis and biliary duct atresia].
AB  - We previously recognized the presence of HPV-DNA in cases of idiopathic neonatal
      giant cell hepatitis (INGCH) and extrahepatic biliary duct atresia (EBDA) in
      archivated tissue using the PCR technique. In order to investigate a possible
      vertical transmission we looked for the presence of HPV-DNA in cervical swabs in
      the mothers along with formalin-fixed paraffin-embedded hepatic tissue from 3
      infants with INGCH and 4 patients with EBDA by nested-PCR. Cervical smears showed
      koilocytosis consistent with HPV infection in 2 cases. Delivery was vaginal
      except for one that was by cesarean section. All infants were males.
      Amplification of HPV-DNA was demonstrated in all cases, the types being
      concordant in infants and mothers. Although this is a small group, the findings
      appear in line with previous data. The presence of the same type of HPV-DNA in
      the infants' livers and their mothers' cervical swabs is another argument
      supporting the possibility of vertical transmission of the virus.

PMID- 9607072
TI  - [Congenital dilatation of extrahepatic bile ducts].
AB  - The authors present 3 cases of congenital dilatation of extrahepatic bile ducts
      and performed a review of the bibliography of this frequent pathology. They
      concluded that the diagnosis could be difficult in the pre-operatory and the
      cholangeographic methods are the beds. The treatment of choice in the actuality
      is the ++quistectomy with hepaticojejunostomy in "Y of Roux".

PMID- 9607073
TI  - [Intestinal trichobezoar: report of a case].
AB  - Trichobezoars are rare medical entities that must be considered in the
      differential diagnosis of patients with abdominal mass. We describe a case of an
      unsuspected intestinal trichobezoar in a nine years old girl. The patient
      presented an acute lower abdominal pain. We found an echogenic abdominal mass in
      the pelvic sonography. A double contrast barium enema was scheduled and a rapid
      relief of symptoms during the preparation of it was accomplished with the
      expulsion of a mass of hair.

PMID- 9607074
TI  - [Helicobacter pylori: diagnostic methods and PCR value].

PMID- 9607075
TI  - [Neoadjuvant therapy in carcinoma of esophagus].

PMID- 9607076
TI  - [Barrett esophagus and the adenocarcinomas].

PMID- 9607077
TI  - Characterization of host-range mutants of cyanophage N-1.
AB  - Fifteen host-range (h) mutants of cyanophage N-1 were characterized with
      reference to their efficiency of plating, time of appearance, morphology and size
      of plaques on Nostoc muscorum and its three phage-resistant (Nm 1/N-1, Nm 2/N-1
      and Nm 8/N-1) mutants. While phage N-1 did not adsorb to the three phage
      resistant mutants, the h mutants differed one from the other in having lower or
      higher adsorption rate constants on N. muscorum or the phage-resistant mutants.
      The inability of majority of h mutants isolated on Nm 1/N-1 to grow in Nm 8/N-1
      was shown to be due to a failure of adsorption. The h mutants also differed one
      from the other in their reversion (back mutation) frequencies. The lethal doses
      (LD37) required to kill 37% of free phage particles after UV-irradiation, heating
      and ethylenediamine tetraacetate (EDTA) treatment greatly varied. Most of the h
      mutants were found to be considerably more sensitive to UV and thermic
      inactivation than N-1 while they were resistant to EDTA. The h mutants except
      five of them were unable to multiply at 40 degrees C. The significance of these
      features is discussed.

PMID- 9607078
TI  - Cross-protection of mice immunized with different influenza A (H2) strains and
      challenged with viruses of the same HA subtype.
AB  - Cross-protection of mice immunized with inactivated preparations of human and
      avian influenza A (H2) viruses was determined after lethal infection with mouse
      adapted (MA) variants of human A/Jap x Bell/57 (H2N1) and avian A/NJers/78 (H2N3)
      viruses. The MA variants differed from the original strains by acquired virulence
      for mice and changes in the HA antigenicity. These studies indicated that mice
      vaccinated with human influenza A (H2) viruses were satisfactorily protected
      against challenge with A/Jap x Bell/57-MA variant; the survival rate was in the
      range of 61%-88.9%. Immunization of mice with the same viral preparations
      provided lower levels of protection against challenge with A/NJers/78-MA variant.
      Vaccination of mice with the avian influenza A (H2) viruses induced better
      protection than with human strains against challenge with both MA variants.
      Challenge with A/NJers/78-MA variant revealed that 76.2%-95.2% of animals were
      protected when vaccinated with avian influenza virus strains isolated before
      1980, and that the protection reached only 52.4%-60.0% in animals vaccinated with
      strains isolated in 1980-1985. The present study revealed that cross-protection
      experiments in a mouse model could provide necessary information for the
      development of appropriate influenza A (H2) virus vaccines with a potential for
      these viruses to reappear in a human population.

PMID- 9607079
TI  - Molecular variation, evolution and geographical distribution of louping ill
      virus.
AB  - Following the demonstration that the tick-borne encephalitis (TBE) subgroup
      viruses are distributed as a cline across the Northern Hemisphere (Zanotto et
      al., 1995), we have analyzed the dispersal pattern of louping ill (LI) virus, the
      most westerly located member in the cline. A total number of 21 LI or LI-related
      virus E gene sequences have been used for a detailed molecular analysis of the
      evolution, phylogeny and geographical distribution of LI virus in the British
      Isles and Ireland. The results show that LI virus is genetically stable in
      general but minor differences enable its separation into four genetically
      distinct subtypes (genotypes) with clear geographical correlation, designated
      Type 1 in Scotland and England, Type 2 in Scotland, Type 3 in Wales and Type 4 in
      Ireland. These data demonstrate that geographically independent evolution of LI
      viruses has occurred. The molecular systematics and substitutional parameters
      analyses combined with the clinal distribution of the TBE virus complex allow the
      assignment of the origin for both Negishi (NEG) virus and a Norwegian isolate to
      the British Isles. Moreover, proposals for the classification of LI and LI-like
      viruses which cause encephalomyelitis in sheep, goat or cattle are presented.

PMID- 9607080
TI  - Analysis of hepatitis C virus isolates using molecular and serological typing
      methods.
AB  - This study comprised 100 persons with antibodies to hepatitis C virus (HCV),
      including 77 intravenous drug users (IVDUs). They were tested with serological
      HCV typing assays (Murex HCV serotyping 1-6 assay; Chiron RIBA HCV Serotyping
      SIA). Patients with a positive polymerase chain reaction (PCR) for HCV (n = 66)
      were tested with genotyping molecular assays (Inno-Lipa HCV II test; Sorin GEN
      ETI-K HCV typing assay). Comparison of the results of these tests showed that (a)
      92% of samples could be typed by one test at least; 44% could be typed by all
      four tests; 88% could be typed by one serological test at least and 66% by one
      molecular test at least; (b) 81% of the samples successfully tested with both
      serological tests gave comparable results; 95% of the samples successfully tested
      with both molecular tests gave comparable results; (c) when serological and
      molecular tests yielded different results, sequences in the 5'-non-coding (5' NC)
      or E1 regions always confirmed the results of the molecular tests; (d) in case of
      discrepancy between the results of the molecular tests the E1 region sequences
      confirmed the Sorin test results. It is concluded that the molecular tests
      compared gave similar results. The fact that the Murex serological test gave
      comparable results in more than 80% of cases indicates that it is an alternative
      to the molecular tests for routine diagnosis. However, comparison of the results
      of this test with those obtained in patients consulting a hepatology department
      showed that it gave the best results in a population of patients not exposed
      repeatedly to HCV.

PMID- 9607081
TI  - Amplification and sequencing of varicella-zoster virus (VZV) gene 4: point
      mutation in a VZV strain causing chickenpox during pregnancy.
AB  - The varicella-zoster virus (VZV) causes chickenpox (varicella) as the primary
      disease and shingles (zoster) as a recurrent manifestation of infection, both
      being generally benign and self-limiting. While these infections may be severe in
      adults and even life-threatening in immunosuppressed individuals, they may be
      amenable to effective antiviral drugs or varicella-zoster immune globulin,
      provided the treatment is administered early. The prompt diagnosis of VZV
      infections may be accelerated by rapid, sensitive and specific molecular
      techniques such as amplification by polymerase chain reaction (PCR) compared with
      slower and more cumbersome tissue culture and serological procedures. Based on
      the VZV gene 4 which encodes a transcriptional activator, primers were designed
      for use in PCR to amplify a target fragment of 381 bp. Distinct diagnostic bands
      were observed by agarose gel electrophoresis of PCR products of VZV strains
      isolated from 11 varicella and 7 zoster patients in Singapore, as well as of the
      Japanese vaccine Oka strain. The detection sensitivity of this PCR assay was
      determined to be 1 pg of purified VZV DNA equivalent to about 7,000 viral DNA
      copies. No target bands were amplified from negative control templates from five
      related human herpes-viruses and from human DNA. The specificity of the PCR
      products was ensured by direct cycle DNA sequencing, which revealed complete
      identity of the 18 VZV isolates with the published European Dumas strain. The
      strong sequence conservation of the target fragment renders this PCR assay highly
      reliable for detecting the VZV sequence. Only one VZV strain isolated from a
      patient with varicella during pregnancy exhibited a GGA to GAA point mutation at
      codon 46 of gene 4, culminating in the non-conservative substitution of Ser with
      Phe. The predicted secondary structure of the mutant polypeptide portrayed a
      radical alteration, which may influence its function in transcriptional
      activation.

PMID- 9607082
TI  - Transcriptional regulation of the gltA and TLC genes in Rickettsia prowazekii
      growing in a respiration-deficient host cell.
AB  - The regulation of the citrate synthase (gltA) and ATP/ADP translocase (tlc) genes
      of the obligate intracellular bacterium, Rickettsia prowazekii, was analyzed in
      rickettsia-infected respiration-deficient G14 cells. The level of the gltA mRNAII
      and the tlc mRNA was much lower in the total RNA isolated from the infected G14
      cells grown in 1 g/l glucose (low glucose, GL) medium than in that from infected
      G14 cells grown in 4.5 g/l glucose (high glucose, GH) medium. However, the level
      of the gltA mRNAI relative to 16 S rRNA was the same in GL and GH media. An
      increase in the level of the gltA mRNAII and the tlc mRNA could be observed as
      early as 2 hrs after shifting from GL to GH medium. We conclude that, under these
      experimental conditions, the tlc promoter and the gltA promoter P2, but not gltA
      promoter P1, were transcriptionally regulated.

PMID- 9607083
TI  - Different effects of phorbol ester derivates on human immunodeficiency virus 1
      replication in lymphocytic and monocytic human cells.
AB  - The mode of action of the phorbol 12,13-dibutyrate (PDBu) and phorbol 12
      myristate 13-acetate (PMA) on the human immunodeficiency virus 1 (HIV-1)
      replication in human lymphocytes and monocytes was studied. PDBu and PMA appear
      to have similar effects on the regulation of HIV-1 replication in acutely
      infected cells. Here we show a significantly increased replication of HIV-1
      induced by PDBu and PMA in Molt-4 and Jurkat cells, but a reduced replication in
      THP-1 and U-937 cells. Moreover, quantitatively different activity of the two
      derivatives in relation to HIV-1 replication was observed. PDBu proved to be a
      stronger stimulator or suppressor of HIV-1 replication as compared to PMA.
      Although the precise mechanism of the activation of HIV-1 replication by phorbol
      ester derivatives is not clear, it can be assumed that the hydrophilycity of PDBu
      may cause its stronger effect.

PMID- 9607084
TI  - Transduction of antibiotic resistance including imipenem resistance by wild type
      phages from nosocomial strains of Pseudomonas aeruginosa.
AB  - In this report we describe transduction of antibiotic resistance determinants by
      three wild type bacteriophages isolated from three Pseudomonas aeruginosa
      strains. The strains showed evident plaques of a lysis caused by a bacteriophage.
      The strains were identified as lysogenic among 31 imipenem (IMP)-resistant P.
      aeruginosa strains isolated at the National Institute of Oncology in Bratislava.
      The carbenicillin (CAR) resistance determinant was transduced by all the three
      phages to four P. aeruginosa recipients-PAO-1670, ML-M-88, ML-1292 and ML-1008.
      The gentamicin (GEN) resistance was transduced to ML-1008 only. The kanamycin
      (KAN) resistance was transduced in the following systems (combinations): "phage
      AP-37 to M-88", "phage AP-38 to PAO-1670, ML-1292 and M-88", and "phage AP-40 to
      M-88". The IMP resistance determinant was transduced by all the three phages to
      P. aeruginosa recipient strains. All transductant colonies were tested for the
      presence of directly not selected but co-transduced resistance determinants.
      Whereas transductants selected on media with IMP were resistant to five
      antibiotics (IMP, CAR, streptomycin (STR), KAN and GEN), transductants selected
      on CAR, KAN, STR, or GEN were resistant to a block of four of these antibiotics
      but not to IMP.

PMID- 9607085
TI  - Nucleotide sequences of the coat protein genes of two Japanese zucchini yellow
      mosaic virus isolates.
AB  - The nucleotide (nt) sequences of the coat protein (CP) genes of two Japanese
      zucchini yellow mosaic virus (ZYMV) isolates (ZYMV-169 and ZYMV-M) were
      determined. The CP genes of both isolates were 837 nt long and encoded 279 amino
      acids (aa). The nt and deduced aa sequence similarities between the two isolates
      were 92% and 94.6%, respectively. The deduced aa sequences of CPs of the Japanese
      isolates were compared with those of previously reported ZYMV isolates by
      phylogenetic analysis. This comparison lead us to divide all ZMYV isolates into 3
      groups in which ZYMV-169 formed its own distinct group.

PMID- 9607086
TI  - Purification of egg drop syndrome-76 virus by velocity density gradient
      centrifugation. A comparative study.

PMID- 9607087
TI  - Evaluation of an enzyme immunosorbent assay for the diagnosis of Argentine
      haemorrhagic fever.
AB  - To elaborate a set of serological tests for the diagnosis of Argentine
      haemorrhagic fever (AHF), an enzyme-linked immunosorbent assay (ELISA) for
      detection of specific anti-Junin virus (JV) IgG is described, and its performance
      is compared with that of the plaque reduction neutralization test (PRNT). The
      reproducibility, sensitivity, specificity, and confidence limits for positive and
      negative results for ELISA were statistically analysed. The value of 800 was
      demonstrated as the lowest positive titer. Titers > or = 800 varied within one
      (two-fold) dilution in 95.6% of the tests, while the sensitivity and specificity
      were 99.2% and 98.8%, respectively. The assay yielded 1% of false positives and
      0.05% of false negatives. A comparison of ELISA to PRNT in detecting the
      seroconversion for JV was studied by the chi square test (comparison of
      proportions in paired samples) and the K parameter for agreement proportion.
      Comparison of ELISA to PRNT showed no significant difference in the proportions
      of positive and negative results of these assays (P < 0.01), demonstrating an
      equivalent performance (K = 0.98) in the diagnosis of AHF. In addition, the
      simplicity and safety of the procedures involved make this ELISA the most
      suitable test to detect natural human JV infections.

PMID- 9607088
TI  - Detection of bovine herpesvirus 1 (BHV-1) genomic sequences in bovine semen
      inoculated with BHV-1 by polymerase chain reaction.
AB  - Polymerase chain reaction (PCR) technique was applied to detect BHV-1 in bovine
      semen inoculated with BHV-1. The technique was found to be 10(6) times more
      sensitive than a non-isotopic dot-blot hybridization method in detecting viral
      genomic DNA. Of the three primer pairs used, the one chosen from glycoprotein gC
      appeared to be most sensitive as it could detect up to 0.01 TCID50 of BHV-1 in
      the semen. The technique could be useful in screening breeding bulls or samples
      of frozen semen prior to use in artificial insemination.

PMID- 9607089
TI  - Comparison of various methods of detection of different forms of dengue virus
      type 2 RNA in cultured cells.
AB  - In this report, the sensitivity of various methods of detection of dengue virus
      type 2 (DEN-2) sense, antisense, replicative intermediate (RI) and replicative
      form (RF) RNAs in infected mosquito Aedes pseudoscutellaris AP-61 and mammalian
      baby hamster kidney BHK-21 cells is compared. LiCl precipitation was used for
      separation of viral RF RNA from RI RNA. Our results show that reverse
      transcription-polymerase chain reaction (RT-PCR) followed by Southern blot
      analysis and slot blot hybridisation of LiCl-fractionated RNA were the most
      sensitive methods of detection of viral RNA and determination of its single
      stranded form. Northern blot analysis was the least sensitive method of detection
      of any form of viral RNA. Using slot blot hybridisation of LiCl-precipitated RNA,
      viral RI RNA containing de novo synthesised negative strand viral RNA was first
      detected 30 mins after virus inoculation in both cell lines. This is the earliest
      time of detection of DEN viral RNA synthesis in host cells so far reported.
      However, RF RNA could not be detected until 24 hrs post infection (p.i) in AP-61
      and 2 days p.i. in BHK-21 cells, respectively. The sequential order of individual
      forms of viral RNA detected in the infected cells was RI, RF and genomic RNAs.
      Viral RNA was detected in AP-61 cells always earlier than in BHK-21 cells.
      Moreover, the level of viral RNA in AP-61 cells was higher than that in BHK-21
      cells, suggesting that the virus replicated more actively in AP-61 cells. In
      conclusion, the LiCl separation of viral RNA followed by slot blot hybridisation
      was found to be the most sensitive and reliable method of detection of DEN virus
      RI, RF and genomic RNAs in the infected cells. Moreover, this method can be
      applied to determine the replication status of any single-stranded RNA virus in
      the host.

PMID- 9607090
TI  - Transmission of tick-borne bunyaviruses by cofeeding ixodid ticks.
AB  - Palma and Bhanja bunyaviruses replicated in Dermacentor marginatus, D.
      reticulatus, Rhipicephalus sanguineus, R. appendiculatus and Ixodes ricinus ticks
      after parenteral inoculation and appropriate incubation and feeding. Palma virus
      was transmitted to D. marginatus and D. reticulatus males, D. reticulatus and R.
      sanguineus females, and R. appendiculatus nymphs while cofeeding with infected
      ticks on laboratory mice. Bhanja virus was transmitted to D. marginatus males and
      R. appendiculatus nymphs. Laboratory mice developed low levels of viraemia
      detectable only by intracranial (i.c.) inoculation of newborne laboratory mice.

PMID- 9607091
TI  - Release of superoxide anion from polymorphonuclear leukocytes stimulated by
      rubella viral antigen-antibody complex in vitro.
AB  - Using a highly sensitive and specific chemiluminescence (CL) method, we detected
      the release of superoxide anion (O2-.) from human polymorphonuclear leukocytes
      (PMNLs) stimulated by rubella viral antigen-antibody complex (VAAC) adsorbed on
      latex particles. The amount of superoxide anion produced by PMNLs was
      proportional to the amount of VAAC. Neither rubella virus alone nor antibody
      alone, adsorbed on latex particles, stimulated production of superoxide anion by
      PMNLs. It is likely that rubella virus requires the presence of antibody in order
      to be recognized by PMNLs, and that the superoxide anion is somehow involved in
      the disease process of rubella.

PMID- 9607092
TI  - Evaluation of primers for PCR amplification of RNA polymerase gene sequences of
      foot-and-mouth disease virus.
AB  - Eight oligonucleotide primers in 7 different combinations were used to amplify 3D
      gene sequences of foot-and-mouth disease virus (FMDV) by reverse transcription
      polymerase chain reaction (RT-PCR). Six of the primers were designed at this
      laboratory. All the primer combinations could specifically amplify 3D gene
      sequences of FMDV serotypes O, A, and C. The largest fragment amplified was of
      1,393 bp and the smallest was of 208 bp in size. The 1,393 bp fragment included
      sequences from the preceeding P18 region of FMDV genome. The second largest
      fragment of 734 bp included sequences from the 3'-extracistronic region of viral
      genome. The remaining fragments were amplified either from the 3'- or 5'-half of
      the 3D gene. Specific amplification of the entire 3D gene in fragments of
      different size showed sequence conservation in the 3D genomic region of FMDV and
      usefulness of the primers reported in detecting inapparent or persistent FMDV
      infection in susceptible animals by RT-PCR.

PMID- 9607093
TI  - Prevention and treatment of lethal influenza A virus bronchopneumonia in mice by
      monoclonal antibody against haemagglutinin stem region.
AB  - The protective properties of monoclonal antibody (MoAb) C179 directed to the stem
      region of haemagglutinin (HA) H2 that possessed fusion-inhibition and unique
      broad cross-neutralizing activities were examined in a mouse model. The MoAb
      efficiently protected mice against a lethal challenge with pneumovirulent human
      (H1) and avian (H2) strains of influenza A virus. Survival rates in mice that
      received intraperitonealy (i.p.) 1000 micrograms of the MoAb per mouse a day
      before the virus challenge were 90% for H1 and 100% for H2 strain. The dose of
      the MoAb of 100 micrograms per mouse significantly decreased mortality in mice.
      Moreover, the MoAb was also efficient in treatment of lethal bronhopneumonia
      caused by H2 influenza virus. The survival rate in mice that received 1000
      micrograms of the MoAb per mouse 2 days after the virus challenge was 90%, while
      that in the control group was 30% only. These results indicate that the MoAb was
      effective in protection of animals against lethal influenza A infection without
      significant difference between H1 and H2 subtypes. The MoAb exerted significant
      effect in treatment of mice infected with H2 influenza virus. Thus, these data
      allow to suggest that the stem region of HA might be a potential target for
      prevention of influenza virus infection and antiviral therapy.

PMID- 9607094
TI  - Susceptibility of peach GF 305 seedlings and selected herbaceous plants to plum
      pox virus isolates from western Slovakia.
AB  - The susceptibility of peach GF 305 seedlings and herbaceous plants to five plum
      pox virus (PPV) isolates from orchards of western Slovakia was investigated. PPV
      was isolated from diseased plum, apricot and peach trees, and transmitted by chip
      budding to peach GF 305. The herbaceous plants were infected by mechanical
      inoculation. The transmission was analysed by symptomatology and double sandwich
      enzyme-linked immunosorbent assay (DAS-ELISA). Infected peaches developed leaf
      distortion, tissue clearing along the veins and small chlorotic spots (isolate
      BOR-3). With exception of BOR-3, the PPV isolates transmitted from peach caused
      local chlorotic spots on Chenopodium foetidum. The character of symptoms changed
      when a sap from PPV-infected Nicotiana benthamiana was used as virus inoculum.
      From N. benthamiana, the PPV isolates could be transmitted to Pisum sativum, cv.
      Colmo (light green mosaic), N. clevelandii and N. clevelandii x N. glutinosa
      hybrid (latent infection or chlorotic spots).

PMID- 9607095
TI  - Evaluation of immunocapture ELISA for diagnosis of goat pox.
AB  - An immunocapture enzyme-linked immunosorbent assay (IC-ELISA) for the detection
      of goat poxvirus (GPV) antigen in skin biopsy samples obtained from healthy and
      experimentally infected goats as well as from goats from field was evaluated. The
      assay was 80-100% specific and 70-86% sensitive, and was compared with a commonly
      used diagnostic test, namely, the counter immunoelectrophoresis (CIE) test in the
      efficacy for goat pox. Although IC-ELISA was marginally more sensitive than the
      CIE test, the diagnosis of goat pox could be successfully done provided both the
      tests were combined in screening scab suspensions. The IC-ELISA could also
      diagnose sheep poxvirus (SPV) infection.

PMID- 9607096
TI  - Forty years of interferon.
AB  - The nature and mode of action of interferon (IFN) have been intensively studied
      for more than 40 years. In this review, we summarize the current knowledge of IFN
      putting emphasize on transitions in its definition, understanding of its
      physiological role and nomenclature, and on brief characterization of individual
      IFN families. Finally, the evolution of IFN and relations between the IFN
      families are discussed.

PMID- 9607097
TI  - Detection of spotted fever group (SFG) rickettsia in Ixodes ricinus ticks in
      Austria.

PMID- 9607098
TI  - Antiherpetic activity of acyclovir is potentiated by mycophenolic acid.

PMID- 9607099
TI  - Modulation of orphanin FQ or electroacupuncture (EA) on immune function of
      traumatic rats.
AB  - Orphanin FQ(OFQ) is a recently discovered 17-amino acid neuropeptide[1-2]. In
      present paper, influence of intracerebroventricular(ICV) administration of OFQ or
      electroacupuncture(EA) on the surgical trauma-induced inhibition of the splenic
      natural killer(NK) cell activity in rat was observed. The results showed that
      administration of 0.1 microgram(0.0055 nmol) and 1 microgram (0.055 nmol) OFQ had
      no effect on the NK cell activity, while 5 micrograms(2.75 nmol) OFQ reduced the
      NK cell activity in normal rats. However, 0.1 microgram, 1 microgram or 5
      micrograms OFQ were found to antagonise the immune function depression caused by
      surgical trauma. The NK cell activity was reduced in normal rats after repeated
      ICV treatment with antisense oligonucleotide (ASO) complementary to bases of
      translated region of rat OFQ receptor mRNA to block the translation of OFQ
      receptor mRNA into protein. EA stimulation of Zusanli(St. 36) and Lanwei(Extra.
      37) points also obviously improved the immunosuppression produced by trauma. OFQ
      combined with EA showed antagonism on the suppression, but there was no
      significant differences compared with OFQ(ICV) or EA alone. When blocking the
      translation of OFQ receptor mRNA with the ASO, the OFQ induced anti
      immunosuppression effect was completely reversed, but EA still improved the
      inhibition on NK cell activity. The results suggested that the OFQ played a role
      in the regulation of immunosuppression. EA could modulate the suppression of NK
      cell activity induced by surgical trauma. The mechanisms of the modulation of OFQ
      or EA on the immunosuppression induced by surgical trauma need further study.

PMID- 9607100
TI  - Ambulatory device for surface EMG recordings.
AB  - The principles of electromyographic (EMG) analysis can be divided into the
      following groups: signal or motor unit shape analysis, amplitude analysis, multi
      channel or successive time difference analysis, signal frequency composition
      analysis, change of frequency time based analysis based on simultaneous amplitude
      or frequency based analysis or concentric and excentric work based shape and
      amplitude ratio analysis. The aim of this paper is to present an ambulatory
      portable device for surface EMG analysing both for integrated EMG and for
      spectral analysis. The reliability of surface EMG recordings have established.
      The recent new technology gets a possibility to measure by reliable way surface
      EMG on-line during exercise, rehabilitation or occupational conditions. Portable
      EMG measurement unit and analysing program seems to be suitable for documentation
      of the response of rehabilitation programs, effects of physiotherapy, analysing
      the muscle balance and activity of sportsman and for documentation of
      occupational health problems. Automatic interpretation and wide data base for
      patient data makes the system useful in daily practice.

PMID- 9607101
TI  - Acupuncture for pain relief during childbirth.
AB  - BACKGROUND: There are few studies on acupuncture in childbirth despite the
      generally established analgesic effect of acupuncture treatment. METHODS: The
      analgesic effect of acupuncture during childbirth was assessed by comparing the
      need for other pain treatments (epidural analgesia using bupivacaine, pudendal
      nerve block, intramuscular meperidine, nitrous oxide/oxygen, intracutaneous
      sterile water injections) in 90 women given acupuncture (acupuncture group) with
      that in 90 women not given acupuncture (control group). RESULTS: 52 women (58%)
      in the acupuncture group and 13 (14%) in the control group managed their
      deliveries without further pain treatment (p < 0.001). The groups were similar
      with respect to age, pariety, duration of delivery, use of oxytocine and
      incidence of Caesarean section. Acupuncture treatment was found to have no major
      side effects, and 85 women (94%) given acupuncture reported that they would
      reconsider acupuncture in future deliveries. CONCLUSION: Acupuncture reduces the
      need for other methods of analgesia in childbirth.

PMID- 9607102
TI  - Postural equilibrium: functional system and its stabilization by means of
      osteoreflexotherapy.
AB  - Our investigations have confirmed that the osteoreceptive sensory system
      participates in the polysensoric regulation of animal and human posture.
      Experiments with animals have demonstrated that the irritation of osteoreceptors
      by electric pulses leads to osteoreceptive response potentials of the same parts
      of the brain (Deiter's nuclei, cerebellum, caudate nucleus, cortical motor centre
      etc.) which participate in the regulation of animal and human posture and other
      motion acts. Close functional relations have been established between the skin,
      bone, vestibular and muscle sensory systems in the brain structures where the
      osteoreceptive excitation converges. The studies of osteoreceptive sensory system
      have served as a theoretical base for new techniques of posture stabilization.
      These are based on osteoreceptive irritations caused by electrical pulses or by
      intraosseal pressure increase at injections of the physiological solution. It has
      been found that each bone has its own specific role in posture regulation. In all
      cases of bone irritation the posture stabilization of various degrees has been
      confirmed. However, it has been demonstrated that the most effective results have
      been obtained by affecting the processus spinosus of seventh cervical vertebra
      and the lower extermity bones, especially those of tibiae and calcaneus.

PMID- 9607104
TI  - Risky business: proposed reform of the antitrust laws as applied to health care
      provider networks.

PMID- 9607103
TI  - The class action suit as a method of patient empowerment in the managed care
      setting.

PMID- 9607105
TI  - Ashes to ashes: why FDA regulation of tobacco advertising may mark the end of the
      road for the Marlboro man.

PMID- 9607106
TI  - Contracts: health plan coverage for "off label" drug use--I.V. Services of
      America Inc., v. American Consulting Engineers Council Insurance Trust Fund.

PMID- 9607107
TI  - Discrimination: exposure-prone procedures and HIV-infected health care
      professionals--Estate of Mauro v. Borgess Medical Center.

PMID- 9607108
TI  - Biosynthesis, assembly and secretion of coagulation factor VIII.
AB  - Factor VIII is a large complex glycoprotein that is deficient in hemophilia A. It
      has a domain organization consisting of A1-A2-B-A3-C1-C2 where the B domain is a
      heavily glycosylated region that is dispensable for procoagulant activity. Factor
      VIII expression is 10-to 20-fold lower than the homologous coagulation factor V.
      Factor VIII expression is limited due to a low level of steady-state messenger
      RNA in the cytoplasm and inefficient transport of the primary translation product
      from the endoplasmic reticulum to the Golgi apparatus. Within the secretory
      pathway, factor VIII is processed to a heterodimer of the heavy chain (domains A1
      A2-B) in a metal ion association with the light chain (domains A3-C1-C2). Upon
      secretion from the cell, von Willebrand factor binds the light chain of factor
      VIII and stabilizes the factor, preventing degradation. Protein folding within
      the mammalian secretory pathway is facilitated by molecular chaperones. Within
      the endoplasmic reticulum, factor VIII exhibits stable interaction with protein
      chaperones identified as the immunoglobulin-binding protein (BiP), calnexin and
      calreticulin. BiP is a peptide-dependent ATPase that interacts with exposed
      hydrophobic surfaces on unfolded proteins or unassembled protein subunits. A
      potential BiP binding site within factor VIII has been identified. Mutation of a
      single amino acid residue in the potential BiP binding site increased the
      secretion efficiency of factor VIII by threefold. Interestingly, the proposed BiP
      binding site is adjacent to a type-1 copper binding site within the A1 domain
      that is required for interaction between the factor VIII A1 domain and the A3
      domain. We propose that Cu(I) binds the type-1 copper ion-binding site in the A1
      domain and provides the essential requirement for a stable interaction between
      the heavy and light chains. Calnexin and calreticulin are transmembrane and
      lumenal proteins, respectively, localized to the endoplasmic reticulum, which
      associate transiently with many soluble and membrane glycoproteins during folding
      and subunit assembly. The calnexin and calreticulin interaction with factor VIII
      occurs primarily through amino-terminal linked oligosaccharides within the
      heavily glycosylated factor VIII B domain and this interaction appears to be
      required for factor VIII secretion. The findings suggest that factor VIII cycles
      through interactions with BiP, calnexin and calreticulin. Although the
      interaction with BiP does not appear to be required for factor VIII secretion,
      data suggest that the calnexin and/or calreticulin interaction is required for
      secretion. The observations suggest a unique requirement for carbohydrate
      processing and calnexin/calreticulin interaction that may limit the productive
      secretion of factor VIII and have implications for approaches towards somatic
      cell gene therapy for hemophilia A.

PMID- 9607109
TI  - Factors impeding efficient expression of factor VIII complementary DNA minigenes.
AB  - Haemophilia A is a bleeding disorder that affects approximately 1 in 10,000
      males. It is caused by a deficiency of functional blood-clotting factor VIII.
      Protein-replacement therapy has been effective as treatment, resulting in a vast
      improvement in the quality of life and dramatically increasing the life
      expectancy of patients. However, therapy with plasma-derived factor VIII has
      allowed the transmission of several human viruses, such as hepatitis viruses,
      human immunodeficiency virus and parvovirus B19. To date, the safety of the
      therapeutic agent is one of the key issues in haemophilia A treatment. The use of
      recombinant factor VIII in haemophilia therapy can avoid the dependence on blood
      derived products and prevent the occurrence of transfusion-associated infections
      with blood-borne pathogens. Gene therapy could go further, and offers the
      prospect of one-time treatment which may, optimally, achieve a total cure of the
      disease. Therefore, haemophilia is an appealing and challenging target for
      somatic-cell gene therapy. On the basis of the phenotypic correction that is
      achieved upon infusion of factor VIII protein, it is expected that an increase in
      the factor VIII plasma level to 10% of the level found in healthy individuals
      would suffice to prevent the manifestation of the bleeding tendency. In this
      paper, we review the progress and the problems of gene therapy for haemophilia,
      with special focus on the problems specifically associated with the transfer and
      expression of human factor VIII complementary DNA.

PMID- 9607110
TI  - Optimization of the human factor VIII complementary DNA expression plasmid for
      gene therapy of hemophilia A.
AB  - While the gene delivery vehicle is critical for the efficacy of human factor VIII
      gene therapy, optimization of the potency and duration of the factor VIII gene
      that is delivered is equally important in light of the poor transcription and
      translation characteristics of this gene. We discuss here a systematic approach
      to optimization of factor VIII complementary DNA expression by analysis of
      specific elements engineered into the transcription unit and other positions in
      the expression plasmid. Within the transcription unit we have engineered
      different 5' and 3' sequence modifications and tested them for factor VIII
      expression in human liver cells. These changes incorporate liver-specific
      promoter and enhancer sequences and regulatory elements affecting RNA export.
      Specifically, the thyroid hormone-binding globulin promoter and alpha 1
      microglobulin/bikunin enhancer were tested and a synthetic 5' intron was compared
      to a 3' post-transcriptional regulatory element on factor VIII expression levels.
      For translation optimization, a leader sequence was designed to be of optimum
      length, have no RNA secondary structure and contain the optimal translation
      initiation sequence. Finally, we discuss areas for plasmid optimization, which
      include removal of near-consensus splicing sequences, the inclusion of strong
      transcription termination elements and the use of autonomous replicating plasmid
      sequences for episomal maintenance and enhanced plasmid retention for duration of
      gene expression.

PMID- 9607111
TI  - Non-viral gene delivery: vehicle and delivery characterization.
AB  - The development of non-viral gene therapy has been hampered by an inability to
      reproducibly manufacture and characterize delivery system components and final
      formulations. Formation of interpolyelectrolyte complexes as the basis of various
      gene delivery methods has been approached as the first step towards development
      of synthetic viruses. We have found that preparation of interpolyelectrolyte
      complexes from disperse reagents gives a more homogeneous gene delivery vehicle
      than other methods. Methods which increase homogeneity also result in higher
      transfection efficiency in vivo. Expression levels of human growth hormone and
      other reporter proteins in mice confirm the potential of parenteral non-viral
      gene delivery for some therapeutic applications. Serum is demonstrated to inhibit
      transfection efficiency in vivo. Our results suggest that further development of
      methods to manufacture homogeneous disperse non-viral delivery vehicles with
      stealth characteristics may enhance both the potency and reproducibility of gene
      transfer in vivo.

PMID- 9607112
TI  - A new approach to gene therapy.
AB  - Since 1975, different virus vectors have been developed in order to carry
      functional genes for gene transfer. However, no successful clinical trials have
      been reported so far. Recently, a new method for altering a single basepair of
      target DNA was reported using chimeric RNA/DNA oligonucleotides. The replacement
      of the single basepair in the target sequence can reach an efficacy of 20%. In
      patients with hemophilia A or B, the mutations (coagulation factors VIII and IX)
      are well characterized. The mutation-repair method using chimeric RNA/DNA
      oligonucleotides could provide an alternative for the treatment of hemophilia.
      The repaired cells will produce normal protein, like that of non-mutated cells,
      and the expression of the protein will be stable as long as the repaired cells
      survive. Clinically, by increasing the concentration of the functional protein (5
      10%), it is hoped that a severe phenotype can be converted into a milder
      phenotype. The high replacement efficacy of the target sequence and the safety of
      the method make this a likely and promising approach for gene therapy in the
      future. However, no correction has been detected for the mutations in the
      coagulation factor genes factor genes factor IX and von Willebrand factor by this
      method so far.

PMID- 9607113
TI  - Thromboprophylaxis with low molecular mass heparin, 'Fragmin' (dalteparin),
      during pregnancy--a longitudinal safety study.
AB  - Twenty-five women with previous verified thromboembolic complications were
      treated with delteparin (Fragmin) during pregnancy and puerperium. Women with
      known hereditary thrombophilia (antithrombin, protein C and protein S
      deficiencies) or with phospholipid antibodies were excluded. The dose at entry
      was calculated according to body weight and thereafter monitored by anti-FXa
      activity aiming at 0.20-0.40 IU/ml plasma 3 h post injection. Dalteparin or
      dextran was used during delivery. Twenty-two women completed the study and 14 of
      these could be given the same dose throughout pregnancy. There was an increased
      dose response postpartum. There were no thromboembolic recurrences or severe
      bleeding complications. The level of antithrombin activity remained normal. Our
      thrombosis-prone pregnant women had initially increased levels of thrombin
      markers but no further increase was observed during the dalteparin
      thromboprophylaxis. Retrospectively, three heterozygous and three homozygous
      individuals for the FV Leiden mutation leading to activated protein C resistance
      were identified. In conclusion, dalteparin could safely be used as
      thromboprophylaxis during pregnancy in these thrombosis-prone women. Women
      weighing 50-79 kg at entry could be treated with 5000 IU of dalteparin once daily
      during pregnancy, without monitoring. Postpartum, many of the women were given a
      reduced dose.

PMID- 9607114
TI  - PAI-1 inhibition enhances the lysis of the platelet-rich part of arterial-like
      thrombi formed in vitro. A comparative study using thrombi prepared from rat and
      human blood.
AB  - We studied the effects of PRAP-1, a PAI-1-inhibiting polyclonal antibody, on
      tissue-type plasminogen activator (t-PA)-induced lysis of arterial-like thrombi
      prepared in vitro from rat and human blood in a Chandler loop device. The t-PA
      induced lysis of the thrombus head and tail was studied over 5 h. For thrombi
      prepared from rat blood, the lysis ratio head:tail was (mean +/- SD): 0.71 +/-
      0.16 (platelet-poor blood), 0.49 +/- 0.22 (whole blood), and 0.22 +/- 0.12
      (platelet-rich blood). PRAP-1 increased the lysis ratio to 0.68 +/- 0.22 for
      whole-blood thrombi (P < 0.01) and to 0.46 +/- 0.15 for platelet-rich thrombi (P
      < 0.001). For thrombi formed from human whole blood, PRAP-1 increased the lysis
      ratio head:tail from 0.61 +/- 0.18 to 0.95 +/- 0.24 (P < 0.05). These effects of
      PRAP-1 were due to a selective increase in the lysis of the thrombi head. The
      plasminogen activator inhibitor (PAI-1) activity was 7.5 +/- 2.8 (rat) and 3.4 +/
      1.3 (human) times higher in the thrombus head compared with the tail. In thrombi
      prepared from rat whole blood, PRAP-1 decreased the PAI-1 activity of the
      thrombus head only by 38 +/- 7% (P < 0.01), while in thrombi prepared from human
      whole blood the PAI-1 activity of the thrombus head decreased by 83 +/- 4% (P <
      0.001). In conclusion, the lysis resistance of the head of an arterial-like
      thrombus formed in vitro can be partially (rat) or totally (human) normalized by
      inhibition of the PAI-1 activity. The results further suggest that in rat
      arterial-like thrombi a t-PA-inhibiting component, different from PAI-1, is
      present.

PMID- 9607115
TI  - Haemostatic disturbances in burned patients during early excision and skin
      grafting.
AB  - Bleeding is a major problem during early excision of burned skin. Therefore, 13
      severely burned adult patients operated on during the first week after the trauma
      were studied. Blood loss was replaced with crystalloids, colloids and packed red
      cell concentrates (PRC). After ten infused PRCs, four fresh frozen plasma (FFP)
      units were given and thereafter one FFP unit with one PRC unit. Arterial blood
      samples were drawn before anaesthesia (SO), during operation after every four
      units of PRC transfusion (S1-4), 4 h postoperatively (S5) and on the first
      postoperative morning (S6). Prothrombin time (%) and activated partial
      thromboplastin time (s) were abnormal before operation (median values 67%, range
      22-99% and 44 s, range 30-86 s, respectively). Prothrombin time decreased during
      operation and reached the critical level for normal haemostasis at S2.
      Thrombelastography showed decreased clot formation rate and impaired fibrin
      platelet interaction peri- and postoperatively. Fibrinogen and factor VIII
      activity were high preoperatively (median 6.1 g/l and 253%) and the critical
      values for normal haemostasis were not reached. Burned patients have a
      consumption coagulopathy which, in combination with haemodilution during
      operation, results in a clinically significant deficiency of coagulation factors
      II, VII and X, in spite of reactive elevation of coagulation factor VIII and
      fibrinogen.

PMID- 9607116
TI  - The soluble recombinant form of a binding protein/receptor for the globular
      domain of C1q (gC1qR) enhances blood coagulation.
AB  - The gC1qR is a ubiquitously expressed, 33 kDa cellular protein which recognizes
      the globular domains of C1q. Recent evidence suggests that the gC1qR also serves
      as the Zn(++)-dependent endothelial cell binding site for factor XII and high
      molecular-weight kininogen, and activates intrinsic coagulation and kinin
      pathways in purified systems. In addition, activated lymphocytes have been
      reported to release soluble gC1qR. Thus, the present study investigated the
      procoagulant potential of soluble gC1qR in human plasma using the recombinant
      protein (rgC1qR). rgC1qR supported a dose-dependent shortening of extrinsic
      coagulation using the prothrombin time in the presence of diluted (1/50-1/500)
      thromboplastin. Maximum enhancement of the prothrombin time resulted in
      shortening of the clotting time from 78.8 +/- 0.4 s to 68.5 +/- 0.6 s (mean +/-
      SD, n = 8) in the presence of 50 micrograms/ml (1.5 mumol/l) rgC1qR. rgC1qR also
      enhanced the intrinsic pathway of coagulation evaluated in the absence of
      activators of the contact system, as demonstrated by a shortening of the plasma
      recalcification time from 348 +/- 66 s to 140 +/- 23 s (n = 4). rgC1qR, however,
      had no effect on intrinsic coagulation in the presence of undiluted kaolin or
      ellagic acid, and under these conditions failed to shorten the activated partial
      thromboplastin time of factor VIII or factor-IX-deficient plasma. rgC1qR further
      failed to affect thrombin and factor Xa generation assayed using chromogenic
      substrates, and did not enhance thrombin-induced conversion of fibrinogen to
      fibrin. Interestingly, the procoagulant activity of the rgC1qR was measurable in
      either factor-XII- or factor-XI-deficient plasma, suggesting that it was not
      exclusively focused on the contact system of coagulation. Although the mechanism
      of action of gC1qR on blood coagulation remains obscure, the data suggest a
      potential role for this protein in hemostatic and thrombotic events.

PMID- 9607117
TI  - The effects of alcohol on coagulation and fibrinolytic factors: a controlled
      trial.
AB  - Light-to-moderate alcohol intake is associated with a reduced incidence of
      ischaemic cardiovascular events, whilst heavy alcohol intake can predispose
      individuals to stroke. Alcohol-induced changes in coagulation and fibrinolysis
      may be relevant and are the subject of this controlled trial of varying alcohol
      intake in 55 predominantly beer-drinking men. Following 4 weeks stabilization
      maintaining usual drinking habits, participants were randomized to either
      continue usual alcohol intake or to restrict alcohol by changing to low alcohol
      beer for 4 weeks. In a final 4 week period, they crossed over to low or usual
      alcohol intake, respectively. Comparing combined low and usual alcohol periods,
      an increase in mean weekly alcohol intake from 92 to 410 ml (mean daily intake
      from 13 to 58 ml) was associated with a decrease in plasma fibrinogen (by 11%, P
      < 0.001) and platelet count (3%, P < 0.05), but increases in factor VII (7%, P =
      0.001), tissue plasminogen activator (tPA; 16%, P = 0.01) and plasminogen
      activator inhibitor-1 (PAI-1; 21%, P < 0.001). The ratio, tPA/PAI-1, fell from
      0.50 to 0.44 (P = 0.02) confirming the relatively greater increase in PAI-1 with
      alcohol consumption. Two lipid-associated natural anticoagulants, tissue factor
      pathway inhibitor and beta 2-glycoprotein-I, did not change. The substantial
      reduction in plasma fibrinogen with alcohol intake may well contribute to the
      apparent protection alcohol confers against ischaemic coronary and cerebral
      events. The increase in factor VII and relatively greater increase in PAI-1 than
      tPA with alcohol intake may attenuate this benefit and indeed may sufficiently
      predispose individuals to thrombosis to contribute to the increased incidence of
      ischaemic stroke seen in heavier drinkers. The balance of anticoagulant and
      procoagulant and fibrinolytic effects in any individual may vary depending on
      quantity and type of alcoholic beverage ingested, as well as on genetic and other
      variables, all of which merit further study.

PMID- 9607118
TI  - Platelet activation supports the development of venous thrombosis in
      hyperlipidemic rats.
AB  - This investigation sought to determine how different components of the hemostatic
      system affect the development of venous thrombosis in rats displaying
      hyperlipidemia, either on a genetic basis or secondary to metabolic disorders. On
      employing an experimental model of collagen-triggered venous thrombosis, both
      spontaneously hyperlipidemic (Yoshida strain) and streptozotocin-induced diabetic
      rats generated about 2.3-fold greater thrombi than normolipidemic controls. This
      was associated with significant platelet activation, as revealed by increased
      levels of serum thromboxane B2 in diabetics (1.5-fold) as well as in Yoshida (8
      fold) rats, in comparison with controls. In contrast, ex vivo total fibrinolytic
      activity, as measured by euglobulin lysis time, did not differ between normo- and
      hyperlipidemic or diabetic animals. Plasminogen activator inhibitor activity was
      lower in both Yoshida and diabetic rats than in controls. However, tissue-type
      plasminogen activator activity was differently affected by the genetic or the
      diabetes-related hyperlipidemia, showing significantly lower values in Yoshida (
      26%), but significantly higher values in diabetic rats (+29%) than in
      normolipidemic controls. We conclude that platelet activation, rather than
      consistent modifications of the fibrinolytic system, is likely to influence the
      enhanced thrombus development associated with primary or secondary forms of
      hyperlipidemia.

PMID- 9607119
TI  - Association between carotid atherosclerosis and hemostatic markers in patients
      with cerebral small artery disease.
AB  - The purposes of this study were to investigate the association between carotid
      atherosclerosis and hemostatic markers, and to elucidate the difference in
      hemostatic markers between intima-media thickening and plaque formation in
      patients with cerebral small artery disease. We investigated carotid
      atherosclerosis by assessing diffuse intima-media thickness measurements and
      localized plaque using B-mode ultrasonography, and we measured the concentrations
      of plasma fibrinogen, beta-thromboglobulin and platelet factor 4 as markers for
      platelet activation, and the activity of plasma von Willebrand factor as a marker
      for endothelial damage. The intima-media thickness was significantly associated
      with age, male sex, the concentrations of plasma beta-thromboglobulin and
      platelet factor 4, and the activity of plasma von Willebrand factor. The plaque
      score showed a significant association with male sex, the concentration of
      fibrinogen, and the activity of plasma von Willebrand factor. These results may
      indicate that underlying mechanisms are not the same between the intima-media
      thickness and plaque formation. We suggest that hemostatic markers could reflect
      the severity of carotid atherosclerosis in patients with cerebral small artery
      disease, and that preventive antiplatelet therapies against brain infarction
      might be necessary for patients with severe carotid atherosclerosis.

PMID- 9607120
TI  - Cellular activation in response to physical exercise: the effect of platelets and
      granulocytes on monocyte reactivity.
AB  - After physical exercise monocytes have been shown to express more
      lipopolysaccharide (LPS)-induced tissue factor activity compared with monocytes
      at rest. This is in contrast to LPS-induced tumor necrosis factor (TNF)-alpha
      production, which is reduced after physical exercise. Furthermore, LPS-induced
      tissue factor activity in monocytes at rest has been shown to be dependent on
      platelets and granulocytes, whereas LPS-induced TNF-alpha is not affected by
      these cells. The aim of the present study was to test how platelets and
      granulocytes affect LPS-induced tissue factor activity in monocytes observed
      after exercise. This was done by separating the different blood cells before and
      after exercise, followed by recombination of the cells in plasma and
      quantification of LPS-induced tissue factor activity in vitro. Two groups of
      subjects with different aerobic endurance levels were tested to reveal possible
      differences as a result of physical conditioning. The results of the present
      study showed that the major effect of exercise was associated with a change in
      the reactivity of monocytes themselves, since monocytes from blood samples taken
      after running recombined with platelets, and granulocytes showed the greatest
      increase in tissue factor activity. Platelets and granulocytes stressed by
      physical exercise had no further enhancing effect on LPS-induced tissue factor
      activity other than that observed at rest. The lowest LPS-induced tissue factor
      activity in all combinations of blood cells was found in athletes, compared with
      less trained subjects, both at rest and in response to exercise.

PMID- 9607121
TI  - Increased risk of venous thrombosis in carriers of natural anticoagulant
      deficiencies. Results of the family studies of the Spanish Multicenter Study on
      Thrombophilia (EMET study).
AB  - Several studies have demonstrated a higher risk of thrombosis in carriers of
      anticoagulant deficiencies than in non-deficient individuals from families with
      thrombophilia. The prevalences in Spain were established in a multicenter study
      (the EMET study) and all the deficient individuals were invited to recruit all
      available family members to be screened for the same deficiency in order to
      establish the risk of thrombosis in deficient individuals. Five-hundred-and
      eighty-three individuals from 114 families with natural anticoagulant
      deficiencies were analysed. Propositi and relatives with a history of thrombosis
      were asked about the localization and the age at the first episode and whether or
      not it was spontaneous. Three families with antithrombin deficiency, 35 with
      protein C, 60 with protein S, four with plasminogen, four with heparin cofactor
      II, seven with combined deficiencies and one family with dysfibrinogenemia were
      included in the analysis. The risk of thrombosis was increased for individuals
      deficient in antithrombin (adjusted odds ratio 21.23; 95% confidence interval
      5.71-78.94), protein C (adjusted odds ratio 12.62; 95% confidence interval 4.75
      33.51), protein S type I (adjusted odds ratio 19.95; 95% confidence interval 7.40
      53.82), protein S type III (adjusted odds ratio 8.11; 95% confidence interval
      2.66-21.99) or in protein C plus protein S (adjusted odds ratio 8.99; 95%
      confidence interval 2.79-28.93), but not for those deficient in plasminogen or
      heparin cofactor II. The thrombosis-free survival was shortened for deficient
      individuals in antithrombin (median 30 years), protein C (median 46 years),
      protein S type-I (median 48 years), protein S type III (median 61 years) and
      combined protein C and S (median 40 years). In conclusion, individuals carrying
      anticoagulant deficiencies have an increased risk of thrombosis, especially those
      with antithrombin, protein C or type I protein S deficiencies.

PMID- 9607122
TI  - Systemic thrombin generation in cancer patients is correlated with extrinsic
      pathway activation.
AB  - Since the first report by Trousseau in 1865, several experimental and clinical
      studies have established that activation of coagulation is common in cancer.
      However, the biochemical basis of the activation of coagulation in cancer
      patients is still not completely understood. The current most accepted opinion is
      that initiation of coagulation in malignancy is driven primarily by activation of
      the extrinsic (tissue factor-dependent) pathway. In order to further prove that
      such a pathogenetic mechanism is actually involved in cancer patients, we
      correlated the plasma levels of activated factor VIIa (FVIIa), which represent a
      very small fraction of plasma FVII, with some well-established markers of
      systemic thrombin generation. Circulating FVIIa was measured using a prothrombin
      time-based assay that employs a truncated form of human recombinant tissue
      factor, while plasma levels of the thrombin-antithrombin complex, the prothrombin
      fragments 1 + 2 and D-dimer were determined by commercially available ELISA kits.
      The study was carried out in 37 patients with different types of cancer and 20
      healthy controls. Plasma levels of FVIIa were significantly increased while those
      of FVII antigen (FVIIag) were decreased in cancer patients compared with
      controls. Furthermore, the FVIIa/ VIIag ratio was more than two-fold higher in
      cancer patients than in controls. In addition, an excess of thrombin generation
      was observed in cancer patients. Interestingly, a positive correlation between
      the FVIIa/VIIag ratio and the plasma levels of either D-dimer (Spearman's r =
      0.325; P = 0.027) or prothrombin fragments 1 + 2 (r = 0.309; P = 0.034) was
      observed in cancer patients. In conclusion, our study further supports the
      hypothesis that the tissue factor/VIIa complex is the main determinant of
      coagulation activation in cancer patients. Large clinical studies will be
      necessary to determine whether FVIIa and the FVIIa/VIIag ratio are useful
      prognostic factors of thromboembolic events in cancer patients.

PMID- 9607123
TI  - Clinical features of thrombophilia in families with gene defects in protein C or
      protein S combined with factor V Leiden.
AB  - Twenty-nine clinically well-characterized, symptomatic index patients, 15 with
      protein C and 14 with protein S deficiency, in whom the genetic defect had been
      identified, were investigated for the presence of factor V Leiden. In six of 15
      (40%) propositi with protein C and four of 14 (29%) with protein S deficiency,
      factor V Leiden was present. The age at first thrombosis was significantly lower
      (P < 0.001) in the ten propositi with a combined genetic defect (mean age 18.4 +/
      6.6 years) than in those with a single defect (mean age 32.6 +/- 10.4 years).
      Spontaneous occurrence, recurrence and site of thrombosis were similar in
      propositi with the single and the combined defect. Family studies led to the
      identification of a combined defect in 18 individuals from 11 families (11
      propositi and 29 relatives), seven subjects had no abnormality, and in 15 a
      single defect was found. In individuals with a combined defect, thrombosis-free
      survival time was significantly shorter than in individuals with a single defect,
      even after exclusion of index patients. None of the seven individuals without
      genetic abnormality had experienced thrombosis. Our findings indicate a higher
      risk for development of thrombosis in individuals with a combined defect compared
      with those with a single defect.

PMID- 9607124
TI  - Autoantibody inhibits binding of von Willebrand factor to glycoprotein Ib and
      collagen in multiple myeloma: recognition sites present on the A1 loop and A3
      domains of von Willebrand factor.
AB  - A 49-year-old man with multiple myeloma (IgG-lambda Bence-Jones protein positive)
      presented a bleeding tendency: characterized intramuscular hemorrhage.
      Coagulation studies showed a von Willebrand factor (vWF) defect (Duke bleeding
      time > 20 min; ristocetin cofactor activity [vWF:RC] < 6%; significant reduction
      of large multimers of vWF. Mixing study suggested the presence of inhibitor
      directed against vWF:RC activity and collagen binding activity of vWF. The
      inhibitor was identified as an antibody of the IgG class. The inhibitor blocked
      the interaction of vWF with glycoprotein Ib in the presence of ristocetin, as did
      the pepsin-digested fragment of the inhibitor [F(ab)2'], but neither blocked
      botrocetin-mediated interaction of vWF with glycoprotein Ib. They also inhibited
      the binding of vWF to immobilized collagen type I. The inhibitor and the F(ab)2'
      reacted strongly with native vWF and fragment I (amino acids 911-1365) and with
      the 39/34 kDa fragment (amino acids 480/481-718), but not with fragment II (amino
      acids 1366-2050) and fragment III-T2 (heavy chains, amino acids 273-511; light
      chains, amino acids 674-728). We conclude that the IgG antibody inhibits both
      vWF:RC activity and the binding of vWF to collagen by reacting with the epitopes
      present on the A1 loop and A3 domains of vWF.

PMID- 9607125
TI  - Soluble platelet endothelial cell adhesion molecule-1 (sPECAM-1) in inflammatory
      vascular disease, atherosclerotic vascular disease, and in cancer.
AB  - Cell surface adhesion molecule expression is likely to be important in
      inflammation, atherosclerosis and cancer, and soluble forms of many of these
      molecules are present in plasma. We measured levels of the soluble form of
      platelet endothelial cell adhesion molecule-1 (sPECAM) by ELISA in the serum of
      77 patients with frank atherosclerosis, 69 patients with inflammatory connective
      tissue disease, and 39 patients with cancer. Each group of patients was
      controlled by an equal number of age- and sex-matched healthy subjects. There was
      no difference between sPECAM in patients with atherosclerosis and their matched
      controls or between patients with connective tissue disease and their controls.
      However, sPECAM levels were lower (16.6 +/- 5.0 ng/ml, mean +/- SD) in patients
      with cancer than in their controls (21.1 +/- 4.4 ng/ml, P < 0.001). No
      differences were found in sPECAM levels between the major subgroups of each type
      of disease, or as a result of factors such as age, sex or smoking in the
      controls. In contrast to levels of many other soluble adhesion molecules, levels
      of sPECAM are not altered in inflammatory or atherosclerotic vascular disease and
      therefore appear to have little relevance in these conditions. However, there may
      be significant differences in sPECAM levels in patients with low levels in
      cancer. Additional investigations are therefore justified.

PMID- 9607126
TI  - Frequencies of prothrombin 20210 G-->A mutation may be different among races-
      studies on Japanese populations with various forms of thrombotic disorders and
      healthy subjects.

PMID- 9607127
TI  - Comparison of the effect of bezafibrate on improvement of atherogenic
      lipoproteins in Japanese familial combined hyperlipidemic patients with or
      without impaired glucose tolerance.
AB  - The effect of bezafibrate on plasma lipoproteins was investigated in Japanese
      familial combined hyperlipidemic patients with or without an impaired glucose
      tolerance accompanied by a low-density lipoprotein subclass, with the major
      gradient gel peak at a particle diameter of less than 25.5 nm. Bezafibrate
      treatment at a dose of 400 mg/d for 12 weeks produced an antiatherogenic effect
      on lipoprotein profiles, as reflected by a decrease in plasma triglyceride
      levels, an increase in plasma high-density lipoprotein-cholesterol levels,
      induction of the large-size subclass of low-density lipoprotein, and
      disappearance of intermediate-density lipoproteins. The plasma total and low
      density lipoprotein-cholesterol-lowering effect of bezafibrate was significant in
      patients without impaired glucose tolerance but was not significant in patients
      with impaired glucose tolerance. Bezafibrate increased lipoprotein lipase
      activity and decreased the activity of cholesteryl ester transfer protein, both
      in patients with or without impaired glucose tolerance. There was no difference
      in the distribution of signal peptide insertion/deletion or Xbal polymorphisms of
      the apolipoprotein B gene in patients with or without impaired glucose tolerance.
      Mechanisms other than lipoprotein lipase, cholesteryl ester transfer protein
      activities, and an apolipoprotein B gene polymorphism may be responsible for the
      resistance to lowering of plasma total and low-density lipoprotein cholesterol
      levels with bezafibrate treatment in familial combined hyperlipidemic patients
      with impaired glucose tolerance.

PMID- 9607128
TI  - Lowering of serum cholesteryl ester transfer protein--but not
      lecithin:cholesterol acyltransferase--activity levels by hypocholesterolemic
      drugs in the rabbit.
AB  - Cholesteryl ester transfer protein (CETP) and lecithin:cholesterol
      acyltransferase (LCAT) are important factors in the regulation of serum
      lipoprotein metabolism. Rabbits were fed hypocholesterolemic drugs to investigate
      the effect on serum CETP and LCAT activity levels. The activities were assayed
      using exogenous substrate assays and are an estimate of CETP and LCAT mass.
      Groups of eight rabbits were fed a cholesterol-free diet containing either 0.03%
      simvastatin or 1% cholestyramine for 6 weeks. For comparison eight rabbits were
      fed a cholesterol-free control diet without drugs or a diet containing 0.1%
      cholesterol for 6 weeks. Total serum and lipoprotein triglyceride concentrations
      were not different after intervention with the hypocholesterolemic drugs or the
      cholesterol diet. Dietary cholesterol induced higher VLDL, IDL, and LDL
      cholesterol, as well as serum CETP activity, as expected. Serum LCAT activity
      showed little change with intervention. Both simvastatin and cholestyramine
      tended to lead to decreased cholesterol in all lipoprotein fractions and caused a
      significant decrease in serum CETP activity when compared with the control diet.
      Both drugs also caused a significant lower LDL particle concentration, as judged
      from differences in LDL protein levels. Intervention with simvastatin or
      cholestyramine led to relatively cholesterol-poor LDL. These effects on LDL
      concentration and composition were opposite from the effects of cholesterol
      feeding. Differences in the cholesterol contents of VLDL and IDL were comparable
      with those in LDL. The results suggest that decreasing serum CETP activity levels
      by treatment with simvastatin or cholestyramine may contribute to lowering of
      cholesterol apo B-containing lipoproteins. The effects are additional to the well
      known increase in hepatic LDL receptor activity, which is likely to be the most
      important factor in LDL cholesterol lowering by these drugs.

PMID- 9607129
TI  - Probucol inhibits neointimal formation in carotid arteries of
      normocholesterolemic rabbits and the proliferation of cultured rabbit vascular
      smooth muscle cells.
AB  - The proliferation of vascular smooth muscle cells (VSMCs) plays an important role
      in the formation of atherosclerotic lesions and restenosis after angioplasty. It
      has been suggested that probucol inhibits VSMCs proliferation, but this effect
      has not been directly demonstrated. In this study we investigated the effect of
      probucol on neointimal formation after balloon injury in normocholesterolemic
      rabbits and examined whether probucol could inhibit the proliferation of rabbit
      cultured VSMC stimulated by fetal bovine serum (FBS). Probucol inhibited the
      formation of neointima by about 63% 2 weeks after balloon injury. Probucol
      inhibited the increase in the number of cultured VSMCs and bromodeoxyuridine
      (BrdU) incorporation stimulated by 10% FBS in a dose-dependent manner. Also, 10%
      FBS stimulated the activities of mitogen-activated protein kinase (MAP kinase)
      and protein kinase C (PKC) in cultured VSMCs. Probucol inhibited these activities
      in a dose-dependent fashion. These results suggest that probucol may inhibit
      neointimal formation after balloon injury in normocholesterolemic rabbits by
      preventing the proliferation of VSMCs via inactivation of MAP kinase and PKC.

PMID- 9607130
TI  - Chronic low blood pressure: a review.

PMID- 9607131
TI  - Myocardioprotective effects of felodipine in an antihypertensive dosage: an
      experimental study in pigs.
AB  - The objective of this study was to test the hypothesis that treatment with the
      calcium antagonist felodipine in normal clinical dosages may have a myocardio
      protective effect in the event of ischemia followed by reperfusion. Comparing the
      cardioprotective effects of felodipine and an agent of another class allowed the
      influence of blood pressure reduction per se to be evaluated. Twenty open-chest
      pigs were exposed to 45 minutes of myocardial ischemia via occlusion of the left
      anterior descending coronary artery (LAD) followed by 240 minutes of reperfusion.
      Either felodipine (felo group; n = 7) or sodium nitroprusside (SNP group; n = 7)
      was administered intravenously starting at 180 minutes before the LAD occlusion
      in a dose that was intended to reduce the mean arterial blood pressure (MAP) by
      30%. Six pigs (vehicle group) serving as controls received a mixture of
      polyethylene glycol (PEG) and 5% glucose, the vehicles for felodipine and SNP,
      intravenously. MAP in the felo and SNP groups was reduced to 65% and 72% of the
      preinfusion levels, respectively. Infarct size as a percentage of the area at
      risk was 49% in the felo, 73% (P < 0.05) in SNP, and 79% (P < 0.01) in the
      vehicle groups, respectively. Felodipine, given in a dose resulting in plasma
      levels corresponding to the therapeutic range in patients on antihypertensive
      treatment, reduced infarct size following myocardial ischemia/reperfusion.
      Afterload reduction induced by nitroprusside did not influence infarct size.
      Thus, felodipine exerted a myocardioprotective effect unrelated to the mechanism
      of afterload reduction in clinically relevant antihypertensive dosages.

PMID- 9607132
TI  - Effects of long-term digoxin therapy on heart rate variability, baroreceptor
      sensitivity, and exercise capacity in patients with heart failure.
AB  - We evaluated the effects of long-term digoxin therapy on exercise capacity and on
      physiological parameters reflecting autonomic tone in 23 patients with mild to
      moderate heart failure. Before and after maintenance digoxin treatment, all
      patients underwent cardiopulmonary exercise testing and indexes of heart rate
      variability (HRV) and baroreceptor sensitivity (BRS) were measured. Long-term
      digoxin therapy significantly (P < 0.05) increased time domain indexes (rMSSD,
      pNN50) which reflect parasympathetic activity (from 30 +/- 16 to 37 +/- 14 and
      from 8 +/- 9 to 12 +/- 7, respectively). High-frequency (HF) and low-frequency
      (LF) power spectral components also showed a significant increase (from 4.5 +/- 1
      to 5.1 +/- 1 and from 5.4 +/- 1 to 5.8 +/- 1, respectively), but the ratio LF/HF
      decreased, indicating a predominance of vagal activity. The magnitude of these
      changes exhibited a strong negative Pearson correlation coefficient when compared
      with initial values before treatment. BRS increased from 2.95 +/- 1.2 to 5.32 +/-
      3 ms/mmHg (P < 0.05). Oxygen consumption at peak exercise and at the anerobic
      threshold increased significantly (from 17 +/- 3 to 19 +/- 3 mL/kg/min and from
      14.7 +/- 3 to 16.5 +/- 3 mL/kg/min, respectively). A persistent negative
      correlation was found between initial values of HRV and the magnitude of changes
      in exercise capacity. These findings show that long-term digoxin therapy
      increases vagal activity and improves exercise capacity in patients with mild to
      moderate heart failure and seems to exert a more marked therapeutic effect on
      patients with poorer initial autonomic function.

PMID- 9607133
TI  - Effect of cilazapril on ventricular remodeling assessed by Doppler
      echocardiographic assessment and cardiac gene expression.
AB  - The purpose of this study is to determine whether the administration of the ACE
      inhibitor cilazapril can lessen the adverse effects of ventricular remodeling,
      including systolic and diastolic dysfunction, modulation of fetal gene
      expression, increase of collagen genes, and depression of the sarcoplasmic
      reticulum (SR) Ca2+ ATPase gene in a myocardial infarcted (MI) rat model. At 1
      day after MI, the animals were randomly assigned to cilazapril treatment or no
      treatment. We performed Doppler-echocardiographic examinations and measured
      cardiac mRNA in rats at 1 month and 3 months after MI (each group n = 8). The
      weights of the right (RV) and left ventricles (LV) in 1- and 3-month MI rats were
      significantly larger than those of the control rats. Cilazapril significantly
      prevented the increase. The MI rats showed systolic dysfunction, as evidenced by
      decreased fractional shortening (control, 34 +/- 3% vs. MI, 17 +/- 3%; P < 0.01)
      and ejection fraction measured by the modified Simpson's method (control, 61 +/-
      2% vs. MI, 36 +/- 3%; P < 0.01) in rats at 1 month after operation. MI rats
      showed diastolic dysfunction, defined as increased peak early filling velocity,
      increased deceleration rate of the early filling wave, decreased late filling
      velocity, and an increase in the ratio of early filling to late filling velocity.
      Cilazapril significantly prevented systolic and diastolic dysfunction in rats
      after MI. The increases in beta-MHC, alpha-skeletal actin, ANP, and collagen I
      and III mRNAs in the nonischemic LV and RV were significantly suppressed by
      treatment with cilazapril. Depressed SR Ca(2+)-ATPase mRNA (nonischemic LV, 0.7
      fold, P < 0.05 vs. control; RV, 0.5-fold, P < 0.05 vs. control) at 3 months after
      MI was significantly restored to normal levels by cilazapril. Cilazapril improved
      the adverse remodeling process by attenuating the progression of systolic and
      diastolic dysfunction, and prevented abnormal cardiac gene expression following
      MI.

PMID- 9607134
TI  - Vasospastic angina in a patient with chronic lead intoxication: a possible cause
      effect relationship?

PMID- 9607135
TI  - Conversion of atrial fibrillation to sinus rhythm using acute intravenous
      procainamide infusion.
AB  - The efficacy and safety of intravenous procainamide in the conversion of atrial
      fibrillation was investigated. A total of 114 patients without severe heart
      failure were randomized to receive either intravenous procainamide (1 g over 30
      minutes, followed by an infusion of 2 mg/min over 1 hour) or placebo in a double
      blind trial. Digoxin (0.5 mg intravenously) was administered to all patients who
      had not previously been receiving digoxin. Treatment was considered successful if
      sinus rhythm was restored within 1 hour after starting the infusion. Conversion
      to sinus rhythm was achieved in 29 (50.9%) of the 57 patients treated with
      procainamide and in 16 (28.1%) of the 57 who received placebo (P approximately
      0.012). When the duration of the atrial fibrillation was < or = 48 hours,
      conversion to sinus rhythm was achieved in 29 (69%) of the 42 patients receiving
      procainamide and in 16 (38.1%) of those receiving placebo (P approximately
      0.004). None of the patients with atrial fibrillation lasting > or = 48 hours
      converted to sinus rhythm in either group. Another factor that played a role in
      the restoration of sinus rhythm was the size of the left atrium: the smaller the
      left atrium, the larger the success rate. The results of the study suggest that
      intravenous procainamide is an effective and safe means for the rapid termination
      of atrial fibrillation of recent onset and that its success rate is inversely
      related to the size of the left atrium. However, the drug is ineffective in the
      conversion of atrial fibrillation lasting more than 48 hours.

PMID- 9607136
TI  - Inhibition of isoproterenol-induced tachycardia by azimilide in the isolated
      perfused guinea pig heart.
AB  - The class III antiarrhythmic agent, azimilide, has been shown to inhibit
      dihydroalprenolol binding to the beta-adrenergic receptor of rat brain and heart
      in an in-vitro ligand-binding assay. Azimilide, was assessed for beta-adrenergic
      activity, either agonist or antagonist, in the isolated perfused guinea pig heart
      in comparison with class III reference agents and the class II agent,
      propranolol. Varying concentrations of compound (0.03-100 microM) were
      retrogradely perfused and the effects on corrected QT interval, baseline heart
      rate, and isoproterenol-stimulated heart rate were measured. Propranolol, dl
      sotalol, azimilide, and d-sotalol inhibited isoproterenol-induced tachycardia
      with IC50 values (the concentration giving 50% inhibition of isoproterenol
      stimulated heart rate) of 0.12, 1.4, 14.6, and 38.0 microM, respectively.
      Clofilium, dofetilide, and sematilide did not affect the action of isoproterenol.
      Dofetilide, clofilium, azimilide, sematilide, dl-sotalol, and d-sotalol increased
      the QTc interval approximately 20 ms at concentrations of 0.1, 0.3, 1.0, 3.0,
      30.0, and 100.0 microM, respectively. The class III antiarrhythmic agents also
      slowed baseline heart rate and exhibited linear R-R and QT-interval relationships
      of similar slope. Azimilide's antagonism of isoproterenol in this isolated heart
      model may reflect a direct receptor interaction or a contribution from the
      bradycardic action of the compound, which distinguishes it from several other
      pure IKr-blocking class III antiarrhythmic agents.

PMID- 9607137
TI  - Progress toward understanding the molecular mechanisms of neurotrophic factor
      signalling.
AB  - Understanding the mechanism of action of the neurotrophic factors is central to
      unravelling of the mysteries of some of the neurodegenerative disorders. In this
      review we will discuss recent advances in our understanding of neurotrophic
      factor signalling in primary cultured neurons, in particular those from the
      superior cervical and dorsal root ganglia, as well as cerebellar granule cells,
      cortical neurons and oligodendrocytes.

PMID- 9607138
TI  - Multisite phosphorylation and the integration of stress signals at p53.
AB  - The p53 tumour suppressor protein is a potent transcription factor that plays a
      major role in the defence against tumour development. p53 exists in a latent form
      that can be activated by a range of stresses including DNA damage, hypoxia,
      cytokines, metabolic changes, viral infection, and activated oncogenes.
      Activation of p53 can lead to cellular growth arrest prior to entry into either S
      phase or mitosis or can trigger cell death through apoptosis. The modification of
      p53 by multisite phosphorylation provides a potential link between stress
      signalling and the regulation of p53 activity, and there is now striking evidence
      that agents that activate p53 can lead to selective changes in its
      phosphorylation status. Topologically, the phosphorylation sites in p53 fall into
      two discrete functional domains. Four phosphorylation events take place within
      the N-terminal 83 amino acids containing the transactivation domain and a region
      involved in transcription-independent growth suppression. At least three of these
      modifications occur in response to agents that cause cellular stress such as DNA
      damage. At the C-terminus, there are three phosphorylation events, each of which
      can independently regulate the specific DNA-binding function of p53, suggesting
      convergent control by different signalling pathways. The multiplicity of these
      covalent modifications and their responsiveness to a wide range of signals
      suggest that p53 activity is tightly and coordinately controlled in response to
      stresses and changes in the cellular environment.

PMID- 9607139
TI  - Membrane association and targeting of prenylated Ras-like GTPases.
AB  - The regulatory function of the Ras-like GTPases in diverse cellular processes,
      such as growth, cell movement, and protein trafficking, is critically dependent
      on targeting to the proper cellular membrane. Prenylation of Ras, Rho/Rac, and
      Rab GTPases, defined as the covalent addition of isoprenyl groups to cysteine
      residues near or at their carboxyl terminus, is the first and necessary step that
      leads to membrane binding and targeting of these proteins. Recent progress on the
      molecular mechanisms of prenylation, membrane association, and targeting of Ras,
      Rho/Rac, and Rab proteins will be reviewed here. The detailed understanding of
      these targeting mechanisms may allow future development of specific therapeutic
      agents that interfere with the function of each one of these proteins.

PMID- 9607140
TI  - G proteins are involved in the suppression of collagen alpha 1 (I) gene
      expression in cultured rat hepatic stellate cells.
AB  - We analyse the role of the G proteins in regulating collagen gene expression by
      measuring collagen alpha 1(I) mRNA levels in cultured hepatic stellate cells in
      basal conditions and after stimulating or inhibiting the major intracellular
      signalling pathways. Stimulation of Gs protein and adenylyl cyclase or the
      addition of 8Br-cAMP to the cells led to a decrease in collagen alpha 1(I) mRNA
      levels, while blocking protein kinase A abolished this effect. Blocking Gi
      protein, phospholipase A2 and C, calcium channels and calmodulin resulted in a
      significant increase in collagen mRNA levels. PKC stimulation led to a marked
      decrease in these levels. These results suggest that collagen gene expression is
      inhibited by a number of intracellular pathways. A Gs and a pertussis toxin
      sensitive G protein seem to initiate cellular response. Transcription factors,
      acting in these pathways, must be identified. However, it seems that they do not
      need to be synthesised.

PMID- 9607141
TI  - Potentiation of insulin-induced phosphatidylinositol-3 kinase activity by phorbol
      ester is mediated by protein kinase C epsilon.
AB  - Our previous results have demonstrated that phorbol 12-myristate 13-acetate (TPA)
      and insulin synergistically stimulate the activity of phosphatidylinositol-3
      kinase (PI-3 kinase) and PI-3 kinase plays an important role in both of TPA
      induced AP-1 activation and cell transformation in tumour promotion sensitive
      (P+) JB6 cells. In the present study, we investigated the role of PKC and its
      isozymes in the synergistic induction of PI-3 kinase by TPA and insulin.
      Bisindolylmaleimide inhibits TPA- and TPA+ insulin-induced PI-3 kinase activity.
      Pretreatment of cells for 24 h with TPA has significant inhibitory effects on TPA
      induced PI-3 kinase activity and abolishes the synergistic effect of TPA and
      insulin-stimulated PI-3 kinase activity. Furthermore, overexpression of a
      dominant negative PKC epsilon, but not dominant negative PKC alpha, blocks the
      synergistic effect of TPA and insulin-induced PI-3 kinase activity. These results
      indicate that the potentiation effect of TPA on insulin-induced PI-3 kinase
      activity is specific through PKC epsilon in JB6 cells.

PMID- 9607142
TI  - Differential regulation of the AP-1 family members by UV irradiation in vitro and
      in vivo.
AB  - We have examined the effect of UVB and solar-simulated irradiation on the
      expression of the AP-1 family of transcription factors and the cytokine IL-6 both
      in cell cultures and in human skin in vivo. UVB irradiation potently induced c
      jun, junB and c-fos mRNA levels in vitro in HaCaT cells. IL-6 mRNA was induced in
      response to UVB irradiation 2-3 h later than c-jun, junB and c-fos mRNAs. In
      human skin in vivo, solar-simulated irradiation induced transiently junB
      expression. Genistein, a tyrosine kinase inhibitor, augmented the induction of c
      jun and junB by UVB irradiation in HaCaT cells. The results of this study provide
      evidence that in addition to c-jun and c-fos, junB is also an essential component
      of the human UV-response. This study also suggests that UVB irradiation regulates
      the AP-1 family by several mechanisms and that the signalling mechanisms of UVB
      irradiation are considerably different from the ones used by UVC irradiation.

PMID- 9607143
TI  - Role of beta ARK in long-term agonist-promoted desensitisation of the beta 2
      adrenergic receptor.
AB  - Phosphorylation of the beta 2-adrenergic receptor (beta 2AR) is the initial event
      that underlies rapid agonist-promoted desensitisation. However, the role of
      phosphorylation in mediating long-term beta 2AR desensitisation is not known. To
      investigate this possibility, we performed intact cell phosphorylation studies
      with COS-7 cells transiently expressing an epitope tagged wild-type beta 2AR and
      found that receptor phosphorylation in cells treated with 1 microM isoproterenol
      for 24 h was approximately 4-fold over the basal state. This finding suggested
      that persistent phosphorylation of the receptor might contribute to functional
      long-term desensitisation which we further explored with mutated beta 2AR lacking
      the determinants of phosphorylation by the beta AR kinase (beta ARK), PKA or
      both. In CHW cells expressing the WT beta 2AR, pretreatment with 1 microM
      isoproterenol for 24 h reduced the isoproterenol-stimulated cAMP response by 82
      +/- 5%. Substitution of the PKA sites with alanines had no effect on the extent
      of desensitisation (77 +/- 6%, P = NS compared to WT). In contrast,
      desensitisation was only 49 +/- 4% (P < 0.001 compared to WT) when the beta ARK
      sites were similarly substituted. Removal of both the beta ARK and PKA sites
      impaired desensitisation to the same extent as the beta ARK mutant. The extent of
      receptor loss (downregulation) was the same among all of the cell lines used and
      therefore could not account for the observed differences in desensitisation.
      Cellular beta ARK activity, assessed by a rhodopsin phosphorylation assay, was
      equivalent in all cell lines and was unaffected by agonist treatment. PKA
      activity, however, was dynamically regulated, increasing 4-fold over basal levels
      after 15 min of isoproterenol and returning to near basal levels after 24 h. The
      lower level of PKA activity after long-term agonist exposure may therefore have
      contributed to the apparent lack of effect of removing PKA sites. Nonetheless,
      long-term desensitisation was clearly attenuated with beta 2AR lacking beta ARK
      phosphorylation sites. These findings show that in addition to its role in
      regulating short-term desensitisation, beta ARK-mediated phosphorylation is an
      important mechanism underlying long-term desensitisation of the beta 2AR as well.

PMID- 9607144
TI  - Dimethylsulfoxide-induced cell death of murine erythroleukemia cells exposed to
      ionising radiation.
AB  - The present investigation was aimed at studying the effects of dimethylsulfoxide
      (DMSO) in combination with high dose (15 and 60 Gy) ionising radiation on the
      growth and differentiation of murine erythroleukemia cells (MEL). The incubation
      with DMSO was performed for 96 h starting immediately after exposure to radiation
      and resulted only in a slight inhibition of cell growth and in a high increase in
      cell death with the induction of both necrosis and apoptosis. The enhancement of
      radiation cytotoxicity was directly related to dose, time in culture and degree
      of differentiation as demonstrated by the severe and multiple aberrations
      observed in light and electron microscopy. Of interest was the observation in
      induced cells of a marked rearrangement of the plasma membrane architecture as
      well as that of the nuclear envelope, with a massive translocation and/or
      decrease in the nuclear pore complexes.

PMID- 9607147
TI  - Webs of drug dependence: towards a political history of tobacco.

PMID- 9607145
TI  - Comparative study of p120 GTPase-activating protein and its point mutant in the
      pleckstrin homology domain.
AB  - GTPase-activating protein (GAP) enhances the intrinsic GTPase activity of
      cellular Ras. In addition to two Src homology 2 (SH2) domains and one Src
      homology 3 (SH3) domain, it contains a pleckstrin homology (PH) domain. The wild
      type or point mutant in the PH domain of p120 GAP (W568A) was expressed by using
      the baculovirus/Sf9 cell system. Direct effects of the G protein beta gamma
      subunit (G beta gamma) and several sphingolipids and the effects of
      phosphorylation by c-Src on the GTPase-stimulating activity of these GAPs on Ras
      were examined by using immunoprecipitates of these GAPs. The activities of
      neither of these GAPs were affected by the addition of G beta gamma, although the
      W568A mutant bound less to G beta gamma compared with the wild type. Several
      sphingolipids had no effect on the activity of these GAPs. Only in the W568A
      mutant was GTPase-stimulating activity reduced by tyrosine phosphorylation by c
      Src.

PMID- 9607148
TI  - 'A microbe of the devil's own make': religion and science in the British Anti
      Tobacco Movement, 1853-1908.

PMID- 9607146
TI  - Homologous and heterologous acute desensitization of vasopressin V1a receptor in
      Xenopus oocytes.
AB  - The mechanism of short-term desensitisation of the V1a vasopressin receptor, a
      phospholipase-C beta linked receptor, was investigated in albino Xenopus oocytes.
      V1a receptors showed rapid agonist-dependent mobilisation of intracellular
      calcium, as detected by aequorin photon emission. Agonist-induced homologous
      short-term desensitisation was evidenced within minutes after stimulation.
      Injection of the second messengers calcium or inositol triphosphate inside the
      cell did not desensitise the receptors. In contrast, protein kinase C (PKC)
      activators 1-oleoyl-2-acetyl-sn-glycerol (OAG) (50 microM) and 1,2-dioctanoyl
      glycerol (DIC8) (10 microM), as well as phorbol -12-myristate-13-acetate (1
      microM) and phorbol -12,13-dibutyrate (1 microM) blunted the calcium
      responsiveness of the V1a receptors. The specific PKC inhibitor
      bisindolylmaleimide (GF109203X) (1 microM) prevented the effect of DIC8 and OAG
      on V1a receptor desensitisation. Heterologous desensitisation induced by agonist
      occurred in oocytes that co-expressed the V1a receptor and the PKC-activating M5
      muscarinic receptor. It was concluded that PKC activation has a role in short
      term desensitisation of the V1a receptor.

PMID- 9607149
TI  - The moral symbolism of tobacco in Dutch genre painting.

PMID- 9607150
TI  - Tobacco and Victorian literature.

PMID- 9607151
TI  - Pushing the weed: the editorializing and advertising of tobacco in the Lancet and
      the British Medical Journal, 1880-1958.

PMID- 9607152
TI  - The first reports on smoking and lung cancer.

PMID- 9607153
TI  - Science and policy: the case of postwar British smoking policy.

PMID- 9607154
TI  - Blow some my way: passive smoking, risk and American culture.

PMID- 9607155
TI  - Smoking and the Royal College of Physicians.

PMID- 9607156
TI  - Ashes to ashes: witness on smoking.

PMID- 9607157
TI  - The story of the Reports on Smoking and Health by the Royal College of
      Physicians.

PMID- 9607158
TI  - ASH: witness on smoking.

PMID- 9607159
TI  - The history of the Norwegian ban on tobacco advertising.

PMID- 9607160
TI  - Advance directives for subjects of research who have fluctuating cognitive
      impairments due to psychotic disorders (such as schizophrenia).
AB  - Current and coincident biomedical advances make this an opportune time to
      encourage research with subjects who have fluctuating cognitive impairments due
      to disorders like schizophrenia. Effecting research with a heterogeneous
      population who may have impaired decision-making capacity that diminishes their
      autonomy, while honoring their liberty and safeguarding their wellbeing, entails
      a rigorous moral charge. Federal regulations and guidelines in regard to research
      involving this population are insufficient and make for additional obstacles. Use
      of research advance directives that allow for the appointment of surrogate
      decision-makers and delineate safeguards for the research subjects may afford
      protection both for subjects and researchers.

PMID- 9607161
TI  - Effectiveness of case management with severely and persistently mentally ill
      people.
AB  - This meta-analytic review synthesizes the findings of 24 published studies
      dealing with the effectiveness of case management with the severely and
      persistently mentally ill. Summative findings were: (1) Overall, case management
      interventions are effective--75% of the clients who participate in them do better
      than the average client who does not; (2) The estimated preventive fraction
      (e.g., prevention of re-hospitalization) among clients who experience relatively
      intense case management service (case loads of 15 or less, 89%) is nearly 30%
      greater than that estimated among similar clients receiving less intensive
      service; and (3) Various case management practice models did not differ
      significantly on estimated effectiveness. Important questions concerning the
      differential effectiveness of case management by specific program, worker,
      client, and client-worker relationship characteristics remain to be answered.

PMID- 9607162
TI  - The participation of families of homeless persons with severe mental illness in
      an outreach intervention.
AB  - OBJECTIVES: This study describes how an Assertive Community Treatment (ACT) team
      which employs a family outreach worker (FOW) interacts with homeless persons with
      severe mental illness and their families. METHODS: The team's ratings of the
      frequency and importance of clients' and treatment team's family contact are
      summarized and compared with independent research reports on patients'
      satisfaction with family relations, housing and hospitalization outcomes.
      RESULTS: 73% of clients had contact with their families. ACT worked with families
      of 61% of clients. ACT had less contact with the families of men (p < .01) and
      substance abusers (p < .01). Client days in stable housing were associated with
      increased ACT family contact (p < .05). CONCLUSIONS: Most ACT clients had
      significant family contact. ACT established contact with most families, and the
      work with families appeared to be associated with higher levels of satisfaction
      with family relations and housing. The role of the FOW should be explored
      further.

PMID- 9607163
TI  - Capacity of rural community mental health centers to treat serious mental
      illness.
AB  - This study evaluates the capacity of rural community mental health center staff
      to treat persons with serious mental illness (SMI). A 20-item survey was mailed
      to 720 providers in 34 community mental health centers (CMHCs) in Iowa. Responses
      were received from 285/680 persons in 32/34 centers. The confidence and interest
      in receiving additional training in tasks necessary for the care of persons with
      SMI was assessed for staff members of various disciplines and both confidence and
      training interest was found to vary by discipline. Recommendations to enhance
      CMHC capacity to treat persons with SMI are discussed.

PMID- 9607164
TI  - Age and mental health services.
AB  - This paper examines how age is related to the use of formal and informal mental
      health services, adjustment to current life conditions, and expectations for
      improvement in future life conditions among a group of persons with serious
      mental illnesses. Interviews with 301 clients of 3 clinics at a public
      psychiatric facility serving West Brooklyn and Staten Island provide the data
      from the study. Outcome measures include nine sorts of help received from
      informal members of the social network and from mental health professionals;
      desires to improve current life conditions; and expectations for future
      improvements in life conditions. Through hierarchical regression procedures we
      examine the impact of age on these outcomes, with controls for self-reported
      symptoms and functioning, sex, and the presence of social network members. The
      results indicate that younger people receive more help from both informal social
      networks and from mental health professionals. In addition, younger people are
      more likely to want improvements in their current life conditions and to be
      optimistic about what the future holds for them. The decline in informal and
      formal support, optimism, and desire to improve their current life situations
      among older clients may be cause for concern among mental health professionals.
      Mental health service providers should give greater recognition to the impact of
      age on mental health service needs among persons with serious mental illnesses.

PMID- 9607165
TI  - A research induction group for clients entering a mental health research project:
      a replication study.
AB  - Through education and discussion, the research induction group introduces mental
      health clients to participation in a research study. The purpose is to help
      clients to understand fully the clinical and research procedures involved in the
      study so that they can make a truly informed decision about whether or not to
      participate. This study replicated a previous study in showing that the research
      induction group resulted in informed decision-making, high rates of participation
      in the clinical services and in the research, and high rates of satisfaction with
      both vocational services and research procedures.

PMID- 9607166
TI  - Treatment boundaries in the case management relationship: a clinical case and
      discussion.
AB  - Case managers provide services in a variety of settings and situations that
      challenge traditional ideas about professional roles and practices. The concepts
      of treatment boundaries, drawn from the psychotherapy literature, are helpful in
      conceptualizing appropriate professional norms in case management. This article
      reviews concepts of treatment boundaries and provides a clinical case for
      illustration and discussion.

PMID- 9607167
TI  - Treatment boundaries in the case management relationship: a behavioral
      perspective.

PMID- 9607168
TI  - Molecular mechanisms of adipocyte differentiation and inhibitory action of pref
      1.
AB  - Commitment and differentiation of adipocytes is governed by transcription factors
      that are under the control of the combinatorial effects of hormonal and cell-cell
      and cell-matrix interaction. Established preadipocyte cell lines, such as 3T3-L1,
      3T3-F442A, and Ob 17, have made it possible to examine the molecular details of
      the differentiation process. Differentiation is accompanied by dramatic increases
      in adipocyte genes, including adipocyte fatty acid-binding protein and lipid
      metabolizing enzymes. Transcription factors PPAR gamma and C/EBP have been shown
      to transactivate some of the adipocyte-expressed genes. By integrating hormonal
      and metabolic cues, these nuclear factors may synergistically function in
      adipocyte lineage determination and differentiation. Adipocyte differentiation
      involves drastic cell shape alterations that are accompanied by changes in
      expression of cytoskeletal and extracellular matrix proteins, including decreases
      in actin and tubulin levels. Pref-1, an EGF-repeat containing transmembrane
      protein, is highly expressed in preadipocytes; this expression is totally
      abolished after differentiation to adipocytes. Pref-1 is inhibitory for adipocyte
      differentiation and processing of transmembrane pref-1 generates a biologically
      active soluble from corresponding to the ectodomain. Interaction of the EGF
      repeats of pref-1 with an as yet unidentified receptor may mediate the inhibitory
      effects of pref-1 in adipocyte differentiation, thereby affecting nuclear events
      accompanying adipogenesis.

PMID- 9607169
TI  - Retinoid-regulated gene expression in neural development.
AB  - The discovery and development of information surrounding the retinoic acid
      receptors (RAR and RXR) has ushered in a new era in understanding the molecular
      mechanism of action of vitamin A in embryonic development and cellular
      differentiation. The mechanisms involved in the regulation of gene expression by
      the retinoids is at least partially known and involves binding of the RAR and RXR
      to retinoic acid response elements. Additional factors, including coregulatory
      proteins, associated regulatory elements, and cell-specific factors, may also be
      involved in determining the specificity of retinoid-regulation of gene expression
      during development. During embryogenesis, retinoids are required for the
      development of the posterior hindbrain and its associated structures, as well as
      for the survival and differentiation of certain classes of neurons and neural
      crest cell derivatives. At least some of the effects of retinoid on hindbrain
      development are related to the regulation of Hox gene expression. Additional
      retinoid-regulated genes have been implicated in nervous system development, and
      the manner in which they lead to phenotypic changes during embryogenesis remains
      to be determined.

PMID- 9607170
TI  - The nuclear matrix: a target for heat shock effects and a determinant for stress
      response.
AB  - The nuclear matrix organizes nuclear DNA into operational DNA domains for
      replication, transcription, and repair. The proteins of the nuclear matrix are
      among the most thermal labile proteins in the cell, undergoing denaturation at 43
      degrees C to 45 degrees C. Heat-shock-induced protein denaturation results in the
      aggregation of proteins to the nuclear matrix. As many as 100 protein changes
      have been observed as a result of this aggregation. Protein aggregation with the
      nuclear matrix is associated with the disruption of nuclear matrix-dependent DNA
      replication, DNA transcription, hnRNA processing, and DNA repair. Disruptions of
      these processes lead to cell death. Nuclear matrix protein changes affect these
      processes by inhibiting DNA supercoiling ability and inhibiting the access to
      matrix-associated DNA. Heat-shock proteins are believed to bind denatured
      proteins and either prevent aggregation or render aggregates more readily
      dissociable. The nuclear matrix appears to be a target for the detrimental
      effects of heat shock and hsp70 serves to protect against such effects. However,
      the nuclear matrix may be involved in the pre- and post-heat shock expression of
      hsp70. We have found a heat-inducible MAR covering the promoter region of murine
      hsp70.3, implying that changes in matrix association are needed for hsp70
      expression. However, the hsp70.1, 70.3, and hsc70t gene family is organized as an
      active gene with respect to the nuclear matrix. Thus, it may be that heat
      inducible genes have a unique matrix-dependent organization. The work presented
      in this review implies that the nuclear matrix is a target for the lethal effects
      of heat and is also a determinant in the protective expression of heat-shock
      genes.

PMID- 9607171
TI  - Overview of strategies for complex genetic diseases.

PMID- 9607172
TI  - The relative power of linkage and association studies for the detection of genes
      involved in hypertension.
AB  - Hypertension is a common disorder that shows a polygenic mode of inheritance.
      Attempts to localize genes involved in the disorder have been carried out using
      both linkage and association tests. The relative merit of these two approaches is
      reviewed with an assessment of their utility for detecting genes involved in
      hypertension. Power calculations were carried out following the method of Risch
      and Merikangas [1], assuming markers were typed across the genome. These show
      that, if there is a single major locus causing susceptibility, non-parametric
      linkage strategies using affected sibpairs may well prove very effective.
      However, if there are a number of genes of small effect, the sample size
      necessary for linkage studies will be prohibitive and a systematic search for
      allelic association may be more appropriate. This is due to the dramatic
      reduction in the excess allele sharing for genes of small effect.

PMID- 9607173
TI  - Approaches to the genetics of cardiovascular disease through genetic field work.
AB  - Successful molecular genetic studies of complex disease require exact, careful
      phenotypization, which is more difficult than that performed for monogenic
      diseases. We have developed a family-oriented field working approach, which
      relies on index patients, their primary care physicians, and a minimum number of
      field working staff. The patients are responsible for recruiting their family
      members. Packets containing an explanatory pamphlet, an informed consent
      statement, a questionnaire, and blood cuvettes are provided. Data are transferred
      from questionnaire and from the laboratory into a computer program that
      facilitates construction of the family tree. We have applied this genetic field
      working approach primarily to patients with lipid disorders. Coupling results
      from genetic field working with modern DNA diagnostic tests such as the
      oligonucleotide ligation assay, has enabled us to effectively identify patients
      with familial hypercholesterolemia in the German population. We are now extending
      genetic field working to hypertension. Hypertension is much more difficult to
      study, because the phenotype is more difficult to discern and document. Both
      complex diseases have the disadvantage that the parents of the index patients are
      likely to already be dead. Nevertheless, we concentrate on the recruitment of
      large pedigrees, sibling pairs with parents whenever possible, and trios
      consisting of index patient and both parents or index patient, parent and
      sibling. With these constellations we can conduct association studies, linkage
      analysis, and novel combinations of both approaches.

PMID- 9607174
TI  - Beta-2 adrenoceptor genetic variation is associated with genetic predisposition
      to essential hypertension: The Bergen Blood Pressure Study.
AB  - We tested the hypothesis that genetic variation in the beta-2 adrenoceptor gene
      is associated with a genetic predisposition to hypertension. Offspring of two
      hypertensive parents were compared with offspring of two normotensive parents.
      The subjects were participants of the Bergen Blood Pressure Study, where couples
      were recruited in 1963 to 1964 and re-examined in 1990. We studied offspring of
      those couples in which both partners were either hypertensive or normotensive in
      both examinations. Twenty-three hypertensive and 22 normotensive families met the
      inclusion criteria. DNA samples from the first born of hypertensive family
      history offspring and normotensive family-history offspring were analyzed. We
      used multiplex sequencing and specifically examined the promoter and the N
      terminal portion of the beta-2 adrenoceptor gene. We found four genetic variants:
      at position -47, a C-->T substitution in the 5' leader cistron causing an Arg-
      >Cys exchange, at -20, a T-->C substitution, at +46 an A-->G substitution leading
      to an Arg16-->Gly exchange, and at +79, a C-->G substitution leading to a Gln27-
      >Glu exchange. The frequency of the Arg16 allele was significantly higher in the
      hypertensive family-history offspring compared to normotensive family-history
      offspring (58% vs. 28% P < 0.011). We constructed haplotypes for the four
      intragenic variants and found significant linkage dysequilibrium. In particular,
      the 5' leader cistron mutant with the wild type alleles at the other loci was
      significantly more frequent in offspring of hypertensive parents, compared to
      offspring of normotensive parents. We also performed a relative risk analysis
      comparing the Gly/Gly, Arg/Gly, and Arg/Arg alleles, which implicated the Arg
      containing allele. Finally, we analyzed the effect of genotype on blood pressure
      in the offspring. We found a significant step-wise effect for all four
      polymorphisms examined. Our data suggest that the Arg variant of the Arg-->Gly
      exchange is associated with parental hypertension and higher blood pressure
      values in this northern European population.

PMID- 9607175
TI  - Role of genetic variants of the renin-angiotensin system in chronic renal
      allograft injury.
AB  - In the the vast majority of patients undergoing kidney transplantation, long-term
      success is markedly limited by a gradual decrease in graft function over time,
      often termed as "chronic rejection" or "chronic allograft injury." Although there
      have been no formal studies examining the role of genetic factors other than
      those related to histocompatibility for the development or progression of chronic
      allograft rejection, it is likely that genetic factors affecting blood pressure
      regulation, mesangial or vascular proliferation, or aspects of inflammatory
      response including thrombosis, chemotaxis, or fibrosis may play an important role
      in this complex syndrome. There is currently little hope that the responsible
      genes can be identified through sib-pair or linkage studies in families.
      Therefore, the study of candidate genes selected on the basis of our current
      understanding of the pathophysiological mechanisms involved in the chronic
      rejection response appears the only feasible approach. Thus far, studies have
      focused mainly on the role of functional genetic variants of the renin
      angiotensin system on renal allograft funding. These studies, however, have not
      identified these variants as important determinants of renal allograft survival.
      Clearly, future studies will have to address the role of other variants of this
      system as well as genes encoding for other systems deemed to be of
      pathophysiological significance for the development and progression of chronic
      transplant injury.

PMID- 9607176
TI  - G proteins and hypertension: an alternative candidate gene approach.
AB  - Hypertension affects approximately 20 to 30% of individuals in industrialized
      countries, and is commonly believed to develop on the basis of both genetic and
      environmental factors. The identification of genes susceptible to the most
      frequent form of hypertension, commonly referred to as "essential" hypertension,
      is hampered by the fact that blood pressure is a poorly defined phenotype that is
      modulated by multiple factors, such as gender, race, body mass etc., and that the
      definition of hypertension depends on a rather arbitrarily chosen cut-off value.
      Hence, more progress has been made in the identification of genes responsible for
      rare autosomal dominant forms of hypertension, such as Liddle's disease. This
      review focuses on an experimental approach that attempts to define candidate
      genes for essential hypertension using immortalized cells from well characterized
      normotensive and hypertensive subjects. From the presently available results, one
      attractive speculation is that an increased intracellular signal transduction
      caused by an enhanced reactivity of Gj-type G proteins represents a genetically
      fixed trait that renders affected individuals susceptible to essential
      hypertension.

PMID- 9607177
TI  - Alpha-adducin polymorphisms and renal sodium handling in essential hypertensive
      patients.
AB  - The relationship between blood pressure and sodium (Na) excretion is less steep
      in hypertension caused by increased renal tubular reabsorption. We recently
      demonstrated that one mutation in rat alpha-adducin gene: (1) is responsible for
      approximately 50% of the hypertension of MHS rats, and (2) stimulates tubular Na
      K pump activity when transfected in renal epithelial cell, suggesting that its
      pressor effect may occur because an increased tubular reabsorption. Linkage and
      association studies demonstrated that the alpha-adducin locus is relevant for
      human hypertension. A point mutation (G460W) was found in human alpha-adducin
      gene, the 460W variant (G/W) is more frequent in hypertensives than in
      normotensives. The aim of this study was to test whether acute changes in body Na
      may differently affect blood pressure in humans as a function of alpha-adducin
      genotype. The pressure-natriuresis relationship was analyzed in 108 hypertensive
      using two different acute maneuvers: Na removal (furosemide 25 mg p.o.) and, two
      days later, Na load (310 mmoles i.v. in 2 hr). We found that 80 patients were
      wild-type homozygous (G/G), 26 were G/W heterozygous, and 2 were W/W homozygous
      with similar blood pressure, age body mass index, gender, plasma and urinary
      sodium and potassium. In basal condition G/W-W/W patients showed a lower plasma
      renin activity and fractional excretion of Na. In either case the pressure
      natriuresis relationship was less sleep in G/W-W/W than in G/G patients,
      obviously negative for Na depletion with furosemide (-0.011 +/- 0.004 vs. -0.002
      +/- 0.002 mm Hg/mumol/min, P < 0.03), and positive for Na load (0.086 +/- 0.02
      vs. 0.027 +/- 0.007 mm Hg/mumol/min, P < 0.001). The finding of reduced slope
      after Na depletion or Na load supports the hypothesis that, as MHS rats, humans
      bearing one W alpha-adducin variant display an increased of renal tubular sodium
      reabsorption.

PMID- 9607178
TI  - Angiotensin I-converting enzyme and angiotensinogen gene interaction and
      prediction of essential hypertension.
AB  - To prove whether the interaction between insertion/deletion (I/D) angiotensin I
      converting enzyme (ACE) and M235T angiotensinogen (AGT) gene polymorphic alleles
      could contribute to causing essential hypertension, we examined subjects from the
      Czech Republic (365 Caucasians total; 202 normotensives and 163 hypertensives).
      Subjects were genotyped for insertion/deletion polymorphism of ACE (I/D ACE,
      intron 16) and for M235T polymorphism of angiotensinogen gene (AGT, exon 2) by
      means of the polymerase chain reaction (PCR) method. The case-control approach
      was used. Fisher's exact test followed by Holmes's test to overcome the problem
      of multiple comparisons were used for the statistical analysis of data. No
      association of single gene allelic variants with essential hypertension was found
      in our population. Having compared only double homozygote combinations, the
      association of the DDMM genotype with essential hypertension was proven (P =
      0.0081). To the contrary, IITT (P = 0.0086) was found more frequently in
      normotensive subjects. We conclude that the interaction of the I/D ACE and M235T
      AGT polymorphic alleles can contribute to essential hypertension, despite the
      absence of single gene associations with the condition.

PMID- 9607179
TI  - The Ob protein (leptin) and the kidney.
AB  - Mutation of the Ob gene, which encodes for leptin, or mutation of the leptin
      receptor leads to obesity in mice. Humans, for the most part, have a positive
      correlation of leptin with body fat mass suggesting possible defects in leptin
      effector mechanisms that may contribute to obesity. As patients on hemodialysis
      have difficulty with appetite, we investigated whether leptin is cleared by the
      kidney and is elevated in hemodialysis patients. In patients with intact renal
      function there was a net renal uptake of 12% of circulating leptin, whereas in
      patients with renal insufficiency there was no renal uptake of leptin. In a
      separate cohort of 36 patients with end-stage renal disease (ESRD), peripheral
      leptin levels factored for body mass index was increased by fourfold as compared
      to a group of healthy controls (N = 338). The leptin receptor exists in a long
      and short form, with the long form primarily expressed in the hypothalamus but
      also in the lungs and kidneys of the mouse. Further studies are necessary to
      clarify the role of leptin in regulating appetite in patients with ESRD and the
      role of leptin in directly affecting kidney function via its receptors.

PMID- 9607180
TI  - Newborn and adult recombinant inbred strains: a tool to search for genetic
      determinants of target organ damage in hypertension.
AB  - It has been proposed that one of the primary events in the development of
      essential hypertension is a growth-related process initiated as early as during
      fetal development. Differences in kidney size have been observed between most rat
      models of hypertension and their respective controls. In this study, we analyzed
      relative kidney size (kidney weight/body wt) in a set of rat recombinant inbred
      strains (RIS) (N = 27) and their progenitors, the spontaneously hypertensive rat
      strain (SHR/Ola) and Brown Norway congenic strain (BN.1x), at two different ages,
      at birth and at 15 weeks. In the progenitors, the relative kidney weight was
      higher in the hypertensive than in the normotensive strain of both the newborn (P
      < 0.001) and adult (P < 0.001) animals. In the RIS, a significant correlation was
      found between the newborn and adult relative kidney weight (r = 0.49, P = 0.01),
      indicating that the two phenotypes share some of their genetic determinants. A
      total genome search of newborn and adult relative kidney weight was performed
      with a total of 453 genetic markers. These analyses revealed several suggestive
      quantitative trait loci (QTL), some of which were, indeed, significant for both
      newborn and adult relative kidney weight (such as, D3Mit9 on rat chromosome 3; r
      = -0.50, P < 0.01; r = -0.47, P < 0.01; respectively). Others, such as the locus
      on rat chromosome 1 (Rt6; r = -0.43, P < 0.05), were significant only for the
      adult relative kidney size. This QTL was found in close proximity to a region
      previously related to susceptibility to hypertensive renal disease in the fawn
      hooded rat and, similarly to that study, its effect was found to be independent
      of blood pressure. Furthermore, a growth pattern of the kidneys after birth,
      evaluated as the difference between the newborn and adult relative kidney weight,
      was also subjected to total genome scan. Several suggestive QTL were identified.
      One of the most significant loci was found at the D1a marker on rat chromosome 17
      (r = -0.51, P < 0.01), which was previously related to the determination of adult
      heart weight in the RIS. In conclusion, the current study demonstrates the
      usefulness of RIS in studies of hypertension-related phenotypes, some of which
      are abnormal before the development of high blood pressure. To better understand
      their role in the pathogenesis of hypertension, studies at different ages are
      needed, which are uniquely feasible in RIS.

PMID- 9607181
TI  - Genetic basis of salt-susceptibility in the Sabra rat model of hypertension.
AB  - The Sabra salt-sensitive SBH/y and salt-resistant SBN/y rats constitute a unique
      experimental model of hypertension in which salt-susceptibility is genetically
      determined and expressed only after salt-loading, without the development of
      spontaneous hypertension. To determine the genetic basis of salt-susceptibility
      in the Sabra rats, the candidate gene and total genome screen approaches were
      adopted. The likely candidate genes in this model incorporate salt-related
      physiological mechanisms such as the nitric oxide system, the arginine
      vasopressin axis and the epithelial sodium channel. In the random genome search
      scheme for culprit genes, SBH/y and SBN/y were cross-bred. A highly unusual and
      composite mode of transmission of salt-susceptibility was found in this cross,
      emphasizing the complexity of the genetic basis of salt-susceptibility. Linkage
      analysis of the entire rat genome with a large number of widely distributed
      microsatellite markers identified three putative gene loci on chromosomes 1 and
      17 that contribute importantly to salt-sensitivity and/or resistance, and
      uncovered sex specificity in the role that salt-susceptibility genes fulfill in
      the development of hypertension.

PMID- 9607182
TI  - Is the nitric oxide system involved in genetic hypertension in Dahl rats?
AB  - To address this issue, a series of genetic tests were carried out. Linkage
      studies showed that the inducible nitric oxide synthase (Nos2) locus cosegregated
      with blood pressure in three F2 populations originated from crosses of Dahl salt
      sensitive (S) rats with rats of various normotensive strains. However, the brain
      nitric oxidase synthase (Nos1) and endothelial nitric oxide synthase (Nos3) loci
      did not cosegregate with blood pressure in five F2 populations. Thus, only Nos2,
      but not Nos1 and Nos3, was considered as a candidate gene for being a
      quantitative trait locus (QTL) for blood pressure in the S rat. To further test
      this hypothesis, congenic strains were constructed by substituting regions on
      Chromosome 10 of the S rat with the homologous regions of the Milan normotensive
      (MNS) rat. Results showed that the chromosome region including Nos2 did not
      contain a blood pressure QTL. In consequence, Nos2 per se is not supported as a
      candidate QTL capable of causing a blood pressure difference between the S and
      MNS rats. Nevertheless, the nitric oxide system appears to be involved
      secondarily in the regulation of blood pressure in the S rat, as evidenced by
      physiological data.

PMID- 9607183
TI  - The Wilms' tumor suppressor WT1: approaches to gene function.
AB  - Occurring with a frequency of 1 in 10,000 live births, Wilms' tumor is one of the
      most common solid tumors of children. The genetic basis of this tumor is highly
      complex and several loci have been shown to be associated with tumor formation.
      Thus far, however, WT1 is the only gene that has been isolated and proven to
      carry mutations within Wilms' tumors. During the last few years, a wealth of
      experiments has been carried out to address the function of WT1 as a tumor
      suppressor and developmental regulator. This review focuses on studies addressing
      WT1 function; new approaches to understand WT1 function in vivo and present
      transgenic data in which WT1 was driven ectopically using a CMV promoter are
      discussed. Our results suggest that ubiquitous expression of WT1 is not
      compatible with embryonic development.

PMID- 9607184
TI  - Vascular development and disorders: molecular analysis and pathogenic insights.

PMID- 9607185
TI  - Antisense oligodesoxynucleotide strategies in renal and cardiovascular disease.
AB  - Antisense oligodesoxynucleotides (ODN) provide a novel strategy to inhibit RNA
      transcription and thereby the synthesis of the gene product. Because antisense
      ODN hybridize with the mRNA strand, they are highly specific. Their backbone
      structure has been modified to phosphorothioates or phosphoamidates so that they
      can better withstand degradation after delivery. We have shown that antisense ODN
      are a useful research tool to elucidate intracellular processes. The example we
      provide involves the inhibition of PKC signaling. Furthermore, we have shown the
      potential clinical utility of antisense treatment. We successfully inhibited the
      expression of the surface adhesion molecule ICAM-1 with antisense ODN in a model
      of reperfusion injury. This model is highly applicable to the problem of delayed
      graft function in humans. However, "getting there" is a major problem and clearly
      less than half the fun. Cationic substances such as lipofectin have worked
      sufficiently well in the experimental setting. Viral gene transfer offers a
      possibility; however, viruses produce an additional series of problems. Liposomes
      may not provide sufficient transfer efficiency. Coating liposomes with viral
      fusion proteins may offer an ideal way with which to deliver the goods into the
      cytoplasm of the target cell.

PMID- 9607186
TI  - Antihypertensive treatment of patients with proteinuric renal diseases: risks or
      benefits of calcium channel blockers?
AB  - In patients with proteinuric renal diseases the rate of progression of renal
      insufficiency is determined by the level of blood pressure and proteinuria. It
      has been demonstrated that strict blood pressure control with angiotensin
      converting enzyme (ACE)-inhibitors or beta-blockers, aimed at reaching values
      below 130/80 mm Hg, attenuates the deterioration of renal function. In general,
      the beneficial effects of these drugs are reflected in a parallel lowering of
      proteinuria. Calcium channel blockers are effective antihypertensive drugs,
      however, their safety in patients with proteinuric renal diseases and renal
      insufficiency may be questioned because of reported untoward effects on urinary
      protein excretion. The present review discusses the potential benefits and risks
      of calcium channel blockers (CCBs) in the treatment of patients with renal
      diseases. To this end we have evaluated the effects of these drugs in animal
      models of progressive renal injury. In these animal models adverse effects of
      CCBs have been reported which are attributed to an impairment of autoregulation.
      In patients with proteinuria, the dihydropyridine CCBs do not lower proteinuria
      despite a reduction of blood pressure. Studies on the effects on the course of
      renal function are limited, however, the available data do suggest that this
      class of CCBs may be less advantageous than other antihypertensive drugs, thus
      arguing against the use of these agents as first-line drugs in patients with
      proteinuric renal diseases. Information on the effects of the non-dihydropyridine
      CCBs is limited to a small number of studies in patients with diabetic renal
      disease. Although the data suggest that these classes of CCBs might be more
      beneficial, more studies are needed, particularly in patients with non-diabetic
      renal diseases, before founded conclusions can be reached.

PMID- 9607187
TI  - An appraisal of T cell subsets and the potential for autoimmune injury.

PMID- 9607188
TI  - Expression of neuronal type nitric oxide synthase and renin in the
      juxtaglomerular apparatus of angiotensin type-1a receptor gene-knockout mice.
AB  - Angiotensin type-1a (AT1a) receptor gene-knockout (AT1a-/-) mice exhibit chronic
      hypotension and renin overproduction. In the kidneys of AT1a-/- mice, the
      activity of neuronal type nitric oxide synthase (N-NOS) was histochemically
      detected by nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase
      (NADPHd) reaction combined with N-NOS immunohistochemistry. The localization of
      renin was detected by immunohistochemistry and the results were analyzed
      morphometrically. The levels of N-NOS and renin mRNA in the renal cortical tissue
      were determined by reverse transcription-PCR and Northern blot analysis,
      respectively. In the renal sections from wild-type mice, NADPHd activity and N
      NOS immunoreactivity were localized to the discrete region of the macula densa in
      contact with the parent glomerulus. In contrast, N-NOS-positive macula densa
      cells were distributed beyond the original location of the macula densa,
      occasionally extending to the opposite side of the distal tubules. The mean
      number of N-NOS positive macula densa cells was significantly increased in AT1a-/
      mice (186 per 100 glomeruli) compared with wild-type mice (65 per 100
      glomeruli). AT1a-/- mice showed 1.4-times higher N-NOS mRNA levels in the renal
      cortical tissues than wild-type mice. The plasma renin activity was significantly
      higher in AT1a-/- mice (205.5 +/- 26.1 ng/ml/hr) than in wild-type mice (8.0 +/-
      0.2 ng/ml/hr). The renin-positive areas per glomerulus and renal renin gene
      expression were 12-times and 2.6-times higher in AT1a-/- mice than in wild-type
      mice, respectively. These abnormalities, however, were less remarkable in AT1a-/-
      mice compared with angiotensinogen-knockout mice. When AT1a-/- mice were fed a
      high-salt diet, the signal intensity of the NADPHd reaction and the number of
      positively-stained macula densa cells were significantly decreased. The levels of
      renal cortical N-NOS mRNA were also suppressed by the treatment. Dietary salt
      loading produced a parallel decrease in plasma renin activity, renal renin
      immunoreactive areas, and the levels of renin mRNA without affecting systemic
      blood pressure. These results provide evidence for the possible involvement of N
      NOS at the macula densa in the increased renin production in AT1a-/- mice.

PMID- 9607189
TI  - Spectrum of early onset nephrotic syndrome associated with WT1 missense
      mutations.
AB  - We investigated 17 children with nephrotic syndrome (NS) of early onset (14 aged
      < 1 year) and rapid progression to end-stage renal disease for the presence of
      mutations in the Wilms' tumor suppressor gene WT1 on chromosome 11. In eight
      children (7 genotypic males) an association with Wilms' tumor and/or ambiguous
      genitalia (Denys-Drash syndrome) was observed. In these eight and two additional
      female patients with NS only constitutional missense mutations in the WT1 gene
      were detected; four children presented the so-called hot spot mutation in exon 9
      (R394N) and six had different mutations in exons 8 and 9 (4 not previously
      described). Renal biopsy showed diffuse mesangial sclerosis in eight and focal
      segmental sclerosis in two cases. End-stage renal disease was reached either
      concomitantly or within four months after onset of NS in seven of ten patients. A
      unilateral Wilms' tumor was found before or concomitant with NS in four children
      (3 males, 1 female). From the seven genotypic males with WT1 mutations, five
      presented ambiguous genitalia and two a female phenotype. No mutation of the WT1
      gene was found in seven other children with isolated congenital or infantile NS
      with or without DMS who appeared to have a slower progression than the first
      group. It is proposed that patients with early onset, rapidly progressive NS and
      diffuse mesangial or focal segmental sclerosis should be tested for WT1 mutations
      to identify those at risk for developing Wilms' tumor.

PMID- 9607190
TI  - TGF-beta 1 dissociates human proximal tubule cell growth and Na(+)-H+ exchange
      activity.
AB  - Stimulation of proximal tubule cell (PTC) growth in a variety of physiological
      and pathological renal conditions is preceded by increased renal production of
      transforming growth factor-beta 1 (TGF-beta 1) and by augmented tubular sodium
      transport via activated sodium hydrogen exchange (NHE). Since TGF-beta 1 has been
      shown to be an important paracrine and autocrine regulator of PTC growth, the
      hypothesis that TGF-beta 1 modulates basal and mitogen-stimulated PTC growth via
      an effect on NHE activity was examined. Confluent, quiescent, human PTC were
      incubated for 24 hours in serum-free media containing vehicle (control) or 1
      ng/ml TGF-beta 1, in the presence or absence of 100 ng/ml insulin-like growth
      factor-1 (IGF-I). Under basal conditions, TGF-beta 1 inhibited thymidine
      incorporation (73.5 +/- 7.3% of control, P < 0.05), but exerted no effect on
      cellular protein content (97.4 +/- 10.7% of control), an index of hypertrophy.
      There was no significant alteration of NHE activity, measured as
      ethylisopropylamiloride (EIPA)-sensitive H+ efflux (2.72 +/- 0.50 vs. control
      3.26 +/- 0.68 mmol/liter/min) or 22Na+ influx (2.20 +/- 0.23 vs. control 2.19 +/-
      0.19 nmol/mg protein/min). When co-incubated with IGF-I. TGF-beta 1 induced
      significant PTC hypertrophy (116.9 +/- 8.2% of control, P < 0.05), which was not
      seen with either agent alone. TGF-beta 1 counteracted the stimulatory effect of
      IGF-I on DNA synthesis (TGF-beta 1 + IGF-I 103.0 +/- 7.3% vs. IGF-I alone 181.2
      +/- 30.3% of control, P < 0.05), but did not affect IGF-I-stimulated EIPA
      sensitive 22Na+ influx (3.63 +/- 0.63 vs. IGF-I alone 3.67 +/- 0.50 nmol/mg
      protein/min, P = NS, both vs. control 2.19 +/- 0.19 nmol/mg protein/min, P <
      0.05). Similar results were obtained when NHE activity was measured as EIPA
      sensitive H+ efflux. Moreover, the kinetics of NHE activation by the combination
      of TGF-beta 1 and IGF-I (involving an increase in Vmax) were identical to that
      previously found for PTC exposed to IGF-I alone. The study demonstrates that TGF
      beta 1 elicits distinct PTC growth responses in the presence and absence of IGF
      I, without modification of NHE activity. The combination of predominant PTC
      hypertrophy and enhanced proximal tubule Na+ reabsorption found in many
      conditions that are associated with renal growth is likely to require the
      integrated actions of both TGF-beta 1 and IGF-I.

PMID- 9607191
TI  - Protein overload stimulates RANTES production by proximal tubular cells depending
      on NF-kappa B activation.
AB  - Abnormal traffic of proteins through the glomerular capillary has an intrinsic
      renal toxicity possibly linked to the subsequent process of proximal tubular
      reabsorption. Here we investigated in vitro the effect of protein overload on
      proximal tubular cell production of RANTES, a nuclear factor-kappa B (NF-kappa B)
      dependent chemokine with potent chemotactic activity for monocytes/macrophages
      and T lymphocytes. Confluent pig LLC-PK1 cells were incubated for 24 and 48 hours
      with Eagle's MEM plus 0.5% FCS containing bovine serum albumin (BSA, 1 to 30
      mg/ml). Tumor necrosis factor-alpha (TNF-alpha; 100 U/ml) was used as a positive
      control. RANTES was measured in cell supernatants by ELISA. Bovine serum albumin
      (BSA) induced a time- and dose-dependent increase in proximal tubular cell RANTES
      production. Selected experiments using transwells showed that the RANTES release
      was predominantly basolateral. The stimulatory effect on tubular RANTES was not
      specific to albumin but was shared by immunoglobulin (Ig) G. We then explored the
      role of NF-kappa B on BSA-induced RANTES. The NF-kappa B inhibitors pyrrolidine
      dithiocarbamate (PDTC; 25 microM) and sodium salicylate (10 mM) significantly
      reduced BSA-induced RANTES production. Electrophoretic mobility shift assay of
      nuclear extracts of LLC-PK1 exposed to BSA revealed an intense NF-kappa B
      activation as early as 30 minutes in a dose-dependent fashion, which was
      inhibited by PDTC. Supershift analysis revealed that the protein subunits of
      activated NF-kappa B were p65/p65 homodimer, p65/cRel, p50/p65 heterodimers.
      Given its chemotactic activity, RANTES released into the interstitium might
      promote inflammatory cell recruitment and contribute to interstitial inflammation
      and renal disease progression.

PMID- 9607192
TI  - Anti-latent TGF-beta binding protein-1 antibody or synthetic oligopeptides
      inhibit extracellular matrix expression induced by stretch in cultured rat
      mesangial cells.
AB  - Transforming growth factor-beta (TGF-beta) is usually secreted as a large latent
      complex associated with latent TGF-beta binding protein-1 (LTBP-1), which is
      known to bind to extracellular matrix (ECM) components. Although the LTBP-ECM
      interaction has been suggested to play a role in the activation and biological
      action of TGF-beta, the precise mechanism is still unclear. In glomerular
      hypertension mesangial cells are believed to perceive the increased cyclic strain
      and we have recently reported that cyclic mechanical stretch in vitro enhances
      the expression of ECM components via an autocrine/paracrine secretion of TGF-beta
      in cultured rat mesangial cells. Therefore, in this study we examined the role of
      LTBP-1 in the stretch-induced, TGF-beta-mediated ECM expression. Mesangial cells
      expressed mRNA for short and long forms of LTBP-1 (LTBP-1S and LTBP-1L,
      respectively). Mesangial cells were subjected to cyclic stretch to provide a
      maximal elongation of 20% at a rate of 60 cycles/min for 24 to 36 hours in the
      presence of polyclonal antibody raised against human LTBP-1 or synthetic
      oligopeptides corresponding to the N-terminal portions of human LTBP-1, which may
      work as competitive inhibitors against the LTBP-ECM association. Both anti-LTBP-1
      antibody (Ab39) and synthetic oligopeptides inhibited the stretch-induced mRNA
      expression of type I collagen and fibronectin in a dose-dependent manner, but the
      inhibition by Ab39 or the oligopeptides was recovered by adding recombinant TGF
      beta. Ab39 or the oligopeptides did not change the effect of exogenously added
      TGF-beta, such as growth-inhibition in mink lung epithelial cells. These results
      suggest that mesangial cells secrete TGF-beta as a large latent complex, and the
      LTBP-ECM interaction may be a pivotal step in TGF-beta action and ECM
      accumulation, providing a new therapeutic strategy against progression of
      glomerulosclerosis and other fibrotic diseases.

PMID- 9607193
TI  - Distinct HLA class II alleles determine antibody response to vaccination with
      hepatitis B surface antigen.
AB  - Major histocompatibility complex (MHC) determinants control antibody production
      in response to protein antigens. Vaccination with hepatitis B surface antigen
      (HBsAg) frequently fails in hemodialyzed patients, but the genetic factors that
      modulate humoral responsiveness are poorly characterized. We studied the
      distribution of HLA class II alleles in 415 hemodialyzed Caucasian patients who
      received a full course of HBsAg vaccination, using class II oligotyping after
      genomic amplification of the DRB1 and DQB1 loci. Phenotype frequencies were
      compared in 114 non responders (anti-HBs antibodies < or = 10 SI units/liter),
      301 responders (anti-HBs antibodies > 10 units/liter) and 471 healthy controls.
      DRB1*01 (DR1) and DRB1*15 (DR15) frequencies were lower in nonresponders than in
      responders and controls (DR1, 12.3% vs. 22.9% and 24.8%, respectively; DR15, 14%
      vs. 22.9% and 25.1%), while DRB1*03 (DR3) and DRB1*14 (DR14) frequencies were
      higher (DR3, 32.5% vs. 16.6% and 25.3%, respectively; DR14, 9.6% vs. 3% and
      6.6%). Overall, 44.5% of DR3 or DR14 patients were nonresponders, compared to
      18.1% of DR1 or DR15 patients (P = 0.0001). In conclusion the humoral response to
      HBsAg vaccine is influenced by class II allelic variants, which differ in their
      capacity to bind and present peptides to T lymphocytes.

PMID- 9607194
TI  - Gene transfer of RANTES elicits autoimmune renal injury in MRL-Fas(1pr) mice.
AB  - We report that the beta-chemokine RANTES, a chemoattractant for macrophages and T
      cells, is up-regulated in the MRL-Fas(1pr) kidney prior to injury, but not normal
      kidneys (MRL-++, C3H-++) and increases with progressive injury. Furthermore, we
      establish an association between RANTES expression in the kidney and renal damage
      using a gene transfer approach. Tubular epithelial cells genetically modified to
      secrete RANTES infused under the renal capsule incites interstitial nephritis in
      MRL-Fas(1pr), but not MRL-++ or C3H-++ mice. RANTES recruits predominantly
      macrophages (M phi) and CD4+ and CD8+ T cells. In contrast, gene transfer of CSF
      1, another molecule up-regulated simultaneously with RANTES in MRL-Fas(1pr)
      kidneys, promotes the influx of M phi, CD4+ T cells and the unique double
      negative (DN) T cells (CD4-, CD8-), which are prominent in diseased MRL-Fas(1pr)
      kidneys. Thus, RANTES and CSF-1 recruit distinct T cell populations into the MRL
      Fas(1pr) kidney. In addition, delivery of RANTES and CSF-1 into the kidney of MRL
      Fas(1pr) mice causes an additive increase in pathology. We suggest that the
      complementary recruitment of T cell populations by RANTES (CD4, CD8) and CSF-1
      (CD4, DN) promotes autoimmune nephritis in MRL-Fas(1pr) mice.

PMID- 9607195
TI  - Effect of hypoxia on proximal tubules isolated from nitric oxide synthase
      knockout mice.
AB  - Nitric oxide (NO) has been shown to be a mediator of hypoxic injury in rat renal
      proximal tubules (PT). However, the role of NO in hypoxic injury to mouse. PT has
      not been examined. The aim of the present study was to determine the effect of
      knockout of nitric oxide synthase (NOS) isoforms on hypoxic injury in mouse PT.
      Mouse PTs were isolated by collagenase digestion and Percoll centrifugation. The
      nonselective NOS inhibitor, N-nitro-L-arginine methyl ester (L-NAME, 10 mM), but
      not its inactive stereoisomer D-NAME, protected against hypoxic injury as
      assessed by LDH release. Carboxy-imidazolineoxyl N-oxide (carboxy-PTIO, 100
      microM), a stable NO scavenger, also afforded cytoprotection against hypoxic
      injury. To determine the role of the different NOS isoforms in the hypoxic
      injury, we examined the effect of hypoxia on PT isolated from knockout mice in
      which either the inducible NOS (iNOS) endothelial NOS (eNOS) or neuronal NOS
      (nNOS) gene was lacking. PT isolated from iNOS knockout mice were resistant to
      hypoxic injury compared to wild-type controls. In contrast, PT isolated from both
      nNOS and eNOS knockout mice were not protected against hypoxic injury. In
      conclusion, the present study demonstrates that NO is a mediator of hypoxic PT
      injury in the mouse and that knockout of the iNOS gene is cytoprotective against
      this hypoxic PT injury.

PMID- 9607196
TI  - Clusterin protects against oxidative stress in vitro through aggregative and
      nonaggregative properties.
AB  - Perturbations of cell interactions, an early event in acute renal injury, have
      important pathophysiologic consequences. We hypothesized that promotion of cell
      interactions protects cells from injury. To test this hypothesis, a single cell
      suspension of LLC-PK1 cells (porcine proximal tubular cell line) treated with
      albumin (control) was compared to cells aggregated with fibrinogen or purified
      human clusterin (aggregation graded 0 to 4). Following aggregation, the cells
      were injured with 1.5 mM hydrogen peroxide (H2O2) for three hours. Cell
      aggregation induced by clusterin but not fibrinogen protected against oxidant
      injury by H2O2. Complete abrogation of cytotoxicity occurred at a clusterin
      concentration of 2.5 micrograms/ml, which resulted in an aggregation score of 1.
      In the absence of aggregation, clusterin at concentrations of 20 and 50
      micrograms/ml, but not lower doses, partially protected against injury induced by
      H2O2. Cell aggregation induced by both clusterin and fibrinogen partially
      protected against endogenously generated oxidant stress induced by incubating LLC
      PK1 cells with aminotriazole and 1-chloro-2,4-dinitrobenzene (CDNB). In
      conclusion, clusterin protects against models of oxidant stress in vitro, whether
      generated by exogenously administered hydrogen peroxide, or from endogenously
      produced peroxide, and such protective effects can accrue from aggregative and
      nonaggregative properties of clusterin.

PMID- 9607197
TI  - Effects of hypertonic stress on transforming growth factor-beta activity in
      normal rat kidney cells.
AB  - Hypertonicity is known to modulate the expression of some genes and the action of
      several cytokines. We evaluated whether hypertonicity would increase the
      expression and/or activity of transforming growth factor-beta (TGF-beta) in
      normal rat kidney (NRK) cells. The bioassay for TGF-beta showed that mature TGF
      beta activity was significantly increased when the cells were cultured in a
      hypertonic medium (500 mOsm/kg). Comparing to the isotonic medium, hypertonicity
      accelerated the increase in TGF-beta activity during the initial 24 hours after
      changing the medium. The activity was increased as the medium osmolality
      increased from 300 to 500 mOsm/kg. Raffinose was found to be the most effective
      in increasing TGF-beta activity. NaCl, glucose, and mannitol also increased TGF
      beta activity. In contrast, total TGF-beta (mature and latent) activity and TGF
      beta mRNA abundance did not change significantly, suggesting that hypertonicity
      activated TGF-beta without affecting the synthesis of TGF-beta. To determine
      whether collagen synthesis was increased by hypertonicity, we examined [3H]
      proline incorporation into NRK cells cultured in hypertonic medium. Proline
      incorporation increased in an osmolality-dependent manner. Raffinose was also the
      most effective solute at increasing the proline incorporation. Furthermore, anti
      TGF-beta antibody prevented the increase in proline incorporation induced by
      hypertonicity. These results suggest that hypertonicity promotes the processing
      of latent TGF-beta to the biologically active form, resulting in the stimulation
      of collagen synthesis in NRK cells.

PMID- 9607198
TI  - Differential effects of glutathione and cysteine on Fe2+, Fe3+, H2O2 and
      myoglobin-induced proximal tubular cell attack.
AB  - Glutathione (GSH) is widely advocated as a cytoprotectant for preventing oxidant
      forms of renal damage. However, in the case of myoglobinuric tubular injury, both
      beneficial and adverse effects have been noted. The purpose of this study was to
      help elucidate this seeming paradox by assessing the impact on thiol
      supplementation on normal tubules and on tubules subjected to individual
      components of heme protein-induced oxidant attack (Fe2+, Fe3+, and H2O2).
      Isolated mouse proximal tubular segments (PTS) were exposed to either GSH or
      cysteine under normal conditions or in the presence of exogenous Fe2+, Fe3+, or
      H2O2. Lethal cell injury (LDH release) and lipid peroxidation (malondialdehyde)
      were then assessed. GSH and cysteine exerted iron dependent, H2O2 independent,
      pro-oxidant effects on normal PTS. Both were also pro-oxidant in the presence of
      an exogenous Fe3+ challenge. In contrast, each attenuated Fe2+ cytotoxicity. The
      importance of iron's redox status on the expression of tubular injury was further
      underscored by the fact that Fe3+ partially blocked Fe2+'s cytotoxic effects. GSH
      mitigated H2O2 toxicity (consistent with a fueling of GSH peroxidase activity).
      Conversely, cysteine promoted H2O2's injurious effects. To assess the impact of
      thiol supplementation on a fully integrated model of heme protein toxicity,
      proximal tubular (HK-2) cells were cultured with myoglobin x 24 hours +/- test
      reactants. Exogenous GSH worsened, while GSH depletion (BSO) protected, against
      myoglobin toxicity (indicating a predominance of GSH's pro-oxidant effects).
      Conversely, cysteine (but not homocysteine) decreased myoglobin toxicity. These
      GSH/cysteine effects were confirmed in LLC-PK1 cells subjected to iron attack. We
      conclude that: (1) GSH and cysteine can exert pro- and anti-oxidant effects,
      depending on the nature of the oxidant challenge and iron's redox status; (2)
      Fe3+ can function as a cytoprotectant, partially offsetting Fe2+ toxicity; and
      (3) cysteine, although potentially pro-oxidant, can mitigate heme protein-induced
      injury. Since the kidney rapidly catabolizes GSH to cysteine, the latter may be
      at least partially responsible for GSH's reported cytoprotective actions against
      myoglobinuric acute renal failure.

PMID- 9607199
TI  - Meprin A, the major matrix degrading enzyme in renal tubules, produces a novel
      nidogen fragment in vitro and in vivo.
AB  - We examined the effect of meprin A, the major matrix degrading metalloproteinase
      in rat kidney, on the laminin-nidogen complex. N-terminal sequence information
      from the most abundant 55 kDa fragment revealed that it was a breakdown product
      of nidogen rather than laminin. In comparison with over 50 nidogen cleavage sites
      produced by other proteases, the meprin A-induced nidogen cleavage site at amino
      acid position 899-900, a glutamine-glycine site in the G3 domain, is unique. In
      addition, these data demonstrate that meprin A degrades the G3 domain of nidogen
      even in the presence of laminin binding, which usually accords protection from
      proteolytic degradation. Meprin A also degraded purified nidogen into similar
      breakdown products. Given that the tubular basement membrane is located on the
      basilar side of the cell, the location of meprin A on the apical brush border
      makes it difficult to envision a role for meprin A in injury-induced basement
      membrane component breakdown. Thus, we examined the possibility that following
      renal tubular epithelial cell injury, meprin A undergoes a translocation to reach
      the underlying basement membrane. After renal ischemia-reperfusion there was a
      marked alteration in meprin A staining with meprin A now distributed throughout
      the renal tubular cell cytoplasm and directly adherent to the tubular basement
      membrane. This was in contrast to the usual linear staining of the brush border
      of tubules in the corticomedullary junction. These data provide unequivocal
      evidence that following injury, meprin A undergoes redistribution and/or
      adherence to the tubular basement membrane. Since in our in vitro studies, we
      identified a distinct meprin-induced 55 kDa nidogen breakdown product, the urine
      was also examined for the presence of nidogen degradation products after rat
      renal ischemia-reperfusion injury. Western blots showed a marked increase in the
      urinary 55 kDa nidogen fragment as early as the first day following ischemia
      reperfusion injury and continuing for six days. Taken together, these in vivo
      data strongly support the notion that the nidogen breakdown products are the
      result of partial degradation of tubular basement membrane by meprin A following
      renal tubular ischemia-reperfusion injury.

PMID- 9607200
TI  - Verotoxins induce apoptosis in human renal tubular epithelium derived cells.
AB  - Apoptosis mediated by verotoxins (VTs) has been identified in a renal carcinoma
      cell line, ACHN cells, which are an in vitro model of renal tubular epithelial
      cells. ACHN cells express the renal tubular marker CD24 as well as globotriaosyl
      ceramide/CD77, the receptor for VTs. VT binding to the ACHN cell surface was
      confirmed by positive staining with antibodies to the VTs. Treatment of ACHN
      cells with VTs induced prompt growth inhibition and cell death, and fragmentation
      of the genomic DNA in cells, typical of apoptosis, was observed. The expression
      of apoptotic antigen 7A6 detected by APO2.7 antibody in ACHN cells further
      supports the occurrence of apoptosis as a result of VT treatment. Cycloheximide
      enhanced VT-mediated apoptosis of ACHN cells, suggesting a strong correlation
      between the inhibition of protein synthesis and VT-mediated apoptosis. Moreover,
      tumor necrosis factor-alpha had a synergistic effect on VT-mediated apoptosis in
      ACHN cells. Considering the above evidence together with the clinical evidence
      showing the presence of apoptosis in the renal epithelium of a HUS patient, our
      results suggest a VT-induced apoptotic mechanism in normal renal tubular
      epithelium that may contribute to the pathogenesis of hemolytic uremic syndrome.

PMID- 9607201
TI  - Cloning of a novel gene in the human kidney homologous to rat munc13s: its
      potential role in diabetic nephropathy.
AB  - Glomerular mesangial cells (MC) are believed to play a pivotal role in
      development of diabetic nephropathy. We employed differential display reverse
      transcription polymerase chain reaction (DDRT-PCR) comparing human MC grown under
      25 mM and 5.5 mM D-glucose and osmolarity control as a first step to identify
      possible candidate genes regulated by hyperglycemia. This strategy resulted in
      cloning of a novel gene in human MC, human munc13 (hmunc13), a human homologue of
      rat munc13s with the N-terminal segment similar to munc13-1 and the C-terminal
      segment more similar to munc13-2. Hmunc13 is also expressed in human kidney
      cortical epithelial cells. By using relative RT-PCR and Northern blot, we have
      confirmed that expression of hmunc13 in MC is up-regulated by high D-glucose
      treatment. Together with previous reports that munc13s binds to diacylglycerol
      (DAG) and that hyperglycemia increases DAG levels, these findings point to a
      potential role of hmunc13 in mediating some of the acute and chronic changes in
      MC produced by exposure to hyperglycemia.

PMID- 9607202
TI  - Effect of 1,25 (OH)2 vitamin D3 on glomerulosclerosis in subtotally
      nephrectomized rats.
AB  - In the past, there has been considerable concern that treatment with active
      vitamin D might accelerate progression independent of hypercalcemia and
      hypercalcuria. Nevertheless, 1,25(OH)2D3 has known antiproliferative properties
      and has also been shown to inhibit renal growth. Since glomerular growth is a
      permissive factor for the development of glomerulosclerosis, we reasoned that
      1,25(OH)2D3 might even attenuate progression. To test this working hypothesis we
      performed two experiments of 8 and 16 weeks duration, respectively, to compare
      subtotally nephrectomized (SNX) rats treated with ethanol and SNX treated with
      1,25(OH)2D3. Control animals were sham operated and pair-fed with SNX animals.
      1,25(OH)2D3 (3 ng/100 g body wt/day) was administered by osmotic minipump.
      1,25(OH)2D3 had no significant effect on systolic blood pressure and only a
      transient effect on weight gain. SNX reduced the number of glomeruli (left
      kidney) from an average of 3.3 x 10(4) to 1.2 x 10(4) per kidney. Mean glomerular
      volume was 3.87 +/- 0.71 x 10(6) microns 3 in sham operated animals and
      significantly (P < 0.05) higher (10.1 +/- 1.75 x 10(6) microns 3) in untreated
      animals 16 weeks after SNX. Glomerular volume was significantly (P < 0.05) less
      in 1,25(OH)2D3 treated SNX [10.1 +/- 1.75 in ethanol vs. 7.04 +/- 1.78 in
      1,25(OH)2D3 treated SNX]. In parallel, there was significantly (P < 0.01) less
      glomerulosclerosis [glomerulosclerosis index 1.16 +/- 0.14 in the ethanol treated
      SNX vs. 0.80 +/- 0.16 in SNX treated with 1,25(OH)2D3] in the eight week
      experiment. Albuminuria was significantly (P < 0.01) lower in 1,25(OH)2D3 treated
      than in ethanol treated SNX (mean 0.785 mg/24 hr, range 0.43 to 1.80, vs. 3.75
      mg/24 hr, 1.29 to 14.2). The morphological data were directionally analogous in a
      second 16 week experiment. Only slight changes of the vascular sclerosis index
      and tubulointerstitial index were seen in SNX and were not affected by
      1,25(OH)2D3 further. To prove that the effect of 1,25(OH)2D3 was independent of
      PTH, parathyreoidectomized SNX rats without or with 1,25(OH)2D3 treatment were
      examined seven days post-SNX. PCNA staining showed suppression of cell
      proliferation. Furthermore, in situ hybridization for transforming growth factor
      B (TGF-beta) showed less vascular and tubular expression in 1,25(OH)2D3 treated
      rats. We conclude that 1,25(OH)2D3 has antiproliferative actions during the
      compensatory growth of nephrons in response to subtotal nephrectomy. These
      effects are independent of PTH. The data document that 1,25(OH)2D3 reduces renal
      cell proliferation and glomerular growth as well as glomerulosclerosis and
      albuminuria as indicators of progressive glomerular damage.

PMID- 9607204
TI  - Cadmium inhibits vacuolar H(+)-ATPase and endocytosis in rat kidney cortex.
AB  - The mechanism of cadmium (Cd)-induced damage in the mammalian proximal tubule
      that is manifested by defects in reabsorption of various compounds, is poorly
      understood. A vacuolar H(+)-ATPase (V-ATPase) in proximal tubule (PT) brush
      border and intracellular vesicles may be affected by Cd, and this may influence
      intracellular vesicle trafficking and reabsorption of the filtered proteins. We
      studied the effects of Cd on V-ATPase and endocytosis in rat renal PT in vivo and
      on acidification mechanisms in isolated renal cortical organelles in vitro. The V
      ATPase activity in brush border membrane (BBM) from Cd-intoxicated rats was 40%
      lower compared to that in control animals. Immunofluorescence studies in cortical
      tissue sections and Western blot studies in BBM from Cd-treated rats showed a
      strongly decreased abundance of the 31 kDa and 70 kDa V-ATPase subunits.
      Functional studies in vivo showed a dramatically diminished endocytosis of
      fluorescein-labeled dextran in PT cells from Cd-treated animals, whereas
      morphological studies revealed a loss of endocytic invaginations and subapical
      vesicles in the same cells. In studies in vitro, Cd inhibited V-ATPase activity
      in a concentration- and time-dependent manner in both BBM and endocytic vesicles,
      whereas in endocytic vesicles, Cd inhibited ATP-driven intravesicular
      acidification and accelerated the dissipation of transmembrane pH gradients. We
      conclude that Cd may impair acidification in cell organelles by (a) causing a
      loss of V-ATPase protein in their limiting membranes, (b) inhibiting the
      intrinsic V-ATPase activity, and (c) dissipating the transmembrane pH gradient.
      This may inhibit endocytosis of filtered proteins and impair vesicle-mediated
      recycling of some membrane transporters, thus contributing to the loss of
      reabsorptive capacity of the PT.

PMID- 9607205
TI  - Identification of structural domains in inter-alpha-trypsin involved in calcium
      oxalate crystallization.
AB  - The urinary glycoprotein that inhibits calcium oxalate (CaOx) crystallization in
      vitro shows a structural similarity to urinary trypsin inhibitor (UTI; recently
      termed bikunin), the light chain of inter-alpha-trypsin inhibitor (I alpha I).
      The functional domains of I alpha I involved in its inhibitory activity of CaOx
      crystallization have been investigated using isolated intact domains of I alpha I
      produced from controlled proteolytic digests of the protein. The fragments
      investigated include the heavy chains of I alpha I, UTI, chondroitinase AC
      treated UTI, and the carboxyl-terminal domain of UTI (termed HI-8). The effects
      of I alpha I and its fragments on the inhibitory activity of CaOx crystallization
      were evaluated in vitro using CaOx crystal aggregation and growth assays, and
      seeded crystal generation assay as well as using crystal matrix protein
      generation assay. UTI, but not the heavy chains of I alpha I, had a discernible
      effect on CaOx crystallization inhibitory activity. Less requirement of the
      carbohydrate moiety of UTI is implicated by the observation that chondroitinase
      AC-treated UTI fragment was also found to inhibit CaOx crystallization with
      almost the same activity as UTI. HI-8 also efficiently inhibited CaOx
      crystallization, while I alpha I showed a weak inhibitory activity. The results
      are almost consistent with a seed crystal generation assay and a crystal
      adsorption inhibition assay, in which I alpha I or its derivatives inhibits
      prothrombin fragment 1 (F1) adsorption to CaOx crystals. In conclusion, these
      results suggest that the part of the I alpha I protein responsible for inhibition
      of CaOx crystallization is the carboxyl-terminal domain of UTI.

PMID- 9607203
TI  - Mesangial cell hypertrophy induced by NH4Cl: role of depressed activities of
      cathepsins due to elevated lysosomal pH.
AB  - Enhanced ammoniagenesis is currently thought to play an important role in renal
      hypertrophy and subsequent tubulointerstitial fibrosis. Under certain conditions
      glomeruli also may be affected by ammonia toxicity. Exposure of glomeruli to
      augmented ammonia levels may occur: (i) in advanced liver diseases due to
      elevated blood ammonia concentrations; (ii) in conditions of enhanced tubular
      ammoniagenesis following cortical "trapping;" and (iii) due to increased ammonia
      formation in the glomeruli in the presence of impaired renal function. To
      elucidate the potential role of ammonia in glomerular injury, we investigated the
      effect of NH4Cl on protein turnover as well as on activities of various
      cathepsins in cultured rat mesangial cells. The results show that NH4Cl (20 mM)
      induced cell hypertrophy as defined by an increase in both cell protein content
      and cell volume (+38% and +10.1%, respectively, after 48 hr). This hypertrophy
      was associated with suppression of the activities of cathepsins B and L + B (
      56.8% and -51.3% after 48 hr) and reduction of protein degradation rate (-61%
      after 48 hr), but without enhanced protein synthesis. Inhibition of Na+/H+
      antiport by amiloride (1 mM) neither prevented the reduction of cathepsin
      activities nor the hypertrophy of the mesangial cells. Upon NH4Cl application
      lysosomal pH was elevated. This alkalinization may be causatively involved in the
      impairment of cathepsin B and L + B due to shifting the lysosomal pH above the
      optimum of their activities. In conclusion, NH4Cl induces hypertrophy but not
      hyperplasia in mesangial cells. This hypertrophy is caused by the reduction of
      protein degradation, mainly due to depressed activities of cathepsin B and L + B
      in the absence of enhanced protein synthesis. A shift of lysosomal pH above the
      optimum of the acidic cathepsins seems to be a key factor in their impaired
      activities in mesangial cells.

PMID- 9607206
TI  - Hypercholesterolemia aggravates radiocontrast nephrotoxicity: protective role of
      L-arginine.
AB  - It is well known that the radiocontrast-induced ARF depends on risk factors often
      associated with compromised renal circulation. Since studies have shown that
      endothelium-dependent vasodilation is impaired in hypercholesterolemia (HC), we
      studied the effect of radiocontrast (RC) administration (6 ml/kg body wt, via
      femoral artery) in salt-depleted rats that were kept on a normal cholesterol (NC)
      or HC diet (4% cholesterol and 1% cholic acid). Inulin clearance (CIn, ml/min/100
      g body wt), renal blood flow (RBF; electromagnetic flowmeter, ml/min/100 g body
      wt), and fractional excretions of sodium, potassium and water (FENa, FEK and
      FEH2O, respectively), cholesterol (mg/dl), and albumin (g/dl) were measured 24
      hours after radiocontrast administration. The administration of RC to HC rats
      (RCHC) resulted in lower values of CIn compared with NC rats (RCNC) and control
      rats: 0.36 +/- 0.085 versus 0.76 +/- 0.13 (RCNC; P < 0.01), versus 0.84 +/- 0.03
      (control HC; P < 0.01), versus 0.87 +/- 0.06 (control NC; P < 0.01).
      Hypercholesterolemia per se did not alter renal function, and control HC versus
      control NC was not significant. Renal blood flow was significantly lower in the
      RCHC when compared to RCNC (4.3 +/- 0.3 vs. 6.1 +/- 0.3; P < 0.001) and to
      control animals (control HC 8.2 +/- 0.3; P < 0.001), and control NC 7.5 +/- 0.33
      (P < 0.001). To study the role of nitric oxide (NO), HC rats were treated with an
      infusion of L-arginine or D-arginine (150 mg via femoral artery) in a 50 mg bolus
      before RC administration and the remaining dose continuously for a period of one
      hour. The administration of L-arginine to RCHC rats resulted in significantly
      higher CIn (0.86 +/- 0.1; P < 0.001) when compared to the untreated rats (RCHC).
      D-arginine did not show a significant difference in CIn (0.49 +/- 0.08). There
      was a considerable difference between D-arginine RCHC and L-arginine RCHC (P <
      0.05). The RBF fall was prevented by L-arginine in RCHC (8.4 +/- 0.23 vs. 4.3 +/-
      0.3; P < 0.001), but it was not prevented by D-arginine (5.1 +/- 0.57; P <
      0.001). Our data suggest that hypercholesterolemia aggravates nephrotoxicity,
      which is attenuated by L-arginine but not by D-arginine administration,
      suggesting that nitric oxide plays a significant role in this model of acute
      renal failure.

PMID- 9607207
TI  - Angiotensin converting enzyme gene I/D polymorphism in essential hypertension and
      nephroangiosclerosis.
AB  - An insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme
      (ACE) gene significantly influences circulating ACE levels and plays a role in
      the development of target organ damage, that is, left ventricular hypertrophy in
      essential hypertension (EH), and microalbuminuria in diabetes mellitus. We have
      examined the role of the I/D polymorphism in essential hypertensive patients with
      renal involvement. The study was divided in two independent protocols. In
      protocol 1, we retrospectively analyzed the ACE genotypes in 37 essential
      hypertensive patients with a clinical and histopathological diagnosis of
      nephroangiosclerosis. In protocol 2, ACE genotypes as well as microalbuminuria
      and renal hemodynamic parameters were investigated in 75 patients with EH with
      normal renal function and a strong family history of hypertension. As control
      group, 75 healthy subjects with BP < 130/85 mm Hg and no family history of
      cardiovascular diseases were studied. The ACE variants were determined by PCR and
      the genotypes were classified as DD, DI and II. In protocol 1, patients with
      nephroangiosclerosis displayed a significant difference in the genotype
      distribution (57% DD, 27% DI, 16% II) when compared to the control population
      (25% DD, 64% DI, 11% II; P < 0.001). There was no significant difference in
      genotype distribution between hypertensive patients with normal renal function
      (protocol 2; 33% DD, 59% DI, 8% II) and the control group. There were no
      differences in age, blood pressure, microalbuminuria and duration of the disease
      among the three genotypes in the EH group from protocol 2. Taken together, these
      findings suggest that the DD genotype of ACE is associated with histopathologic
      proven kidney involvement in patients with EH and that this polymorphism could be
      a potential genetic marker in hypertensives at risk of renal complications.

PMID- 9607208
TI  - Role of increased oxygen free radical activity in the pathogenesis of uremic
      hypertension.
AB  - Earlier studies have demonstrated increased oxygen free radical (OFR) activity,
      diminished antioxidant capacity and reduced OFR-inactivating enzymes in chronic
      renal failure (CRF). Via inactivation of nitric oxide (NO), oxidation of
      arachidonic acid and a direct vasoconstrictive action, OFR can potentially raise
      blood pressure (BP). This study was designed to test the hypothesis that
      increased OFR activity may contribute to CRF hypertension. Four weeks after 5/6
      nephrectomy rats were treated for two weeks with either lazaroid, a potent
      antioxidant and lipid peroxidation inhibitor (CRF-LZ group), or vehicle alone
      (CRF group) by daily gastric gavage. The control group was sham operated and
      placebo treated. The CRF group exhibited significant increases in BP and plasma
      lipid peroxidation product, malondialdehyde (MDA), indicating enhanced OFR
      activity. This was accompanied by decreased urinary nitrate/nitrite (NOx)
      excretion suggesting depressed NO production. LZ therapy normalized plasma MDA
      and significantly ameliorated CRF-induced hypertension. Both MDA and blood
      pressure (BP) rose to values seen in the untreated CRF group within two weeks
      after termination of LZ therapy. Intravenous administration of the hydroxyl
      radical scavenger, dimethylthiourea (DMTU), significantly lowered BP and raised
      urinary NOx excretion. However, no discernible effects were found with either
      superoxide dismutase or catalase (superoxide and H2O2 quenchers). The results
      suggest that increased OFR activity is, in part, responsible for CRF-associated
      HTN. The study further points to hydroxyl radicals as the major source of OFR in
      CRF animals. If substantiated in humans, antioxidant therapy becomes a logical
      adjunct in the management of CRF.

PMID- 9607209
TI  - Renal involvement in Henoch-Schonlein purpura: a multivariate analysis of
      prognostic factors.
AB  - This study is the first report in which the relationship between the progression
      of renal involvement in Henoch-Schonlein purpura (HSP) and various factors was
      evaluated using a multivariate analysis. Sixty-five (33.5%) of 194 patients with
      HSP developed renal involvement from three days to 17 months after the onset of
      the disease. The plasma coagulation factor XIII (F XIII) activity of 97 patients
      was examined, and 51 (54.3%) of them showed a decreased activity. A univariate
      analysis showed that an age at the onset of more than seven years, persistent
      purpura and a decreased F XIII activity all increased the risk of developing
      renal involvement. A Cox regression model analysis indicated severe abdominal
      symptoms, persistent purpura and decreased F XIII activity to be significant risk
      factors and their hazard ratios were 3.26, 11.53 and 2.27, respectively.
      Corticosteroid treatment had a hazard ratio of 0.36 and was considered to
      decrease the risk of developing renal involvement. Based on these findings,
      patients who have the risk factors for renal involvement should be treated with
      corticosteroids at the onset of the disease to prevent developing renal
      involvement.

PMID- 9607210
TI  - Expression of endothelial and inducible nitric oxide synthase in human
      glomerulonephritis.
AB  - The presence of nitric oxide (NO) in the kidney has been implicated in the
      pathogenesis of human glomerulonephritis. However, the exact type of glomerular
      cells that express NO synthase (NOS) and the NOS isoform involved in the local
      production of NO has not been identified in the human diseased kidney. We
      examined the expression of three isoforms of NOS, inducible NOS (iNOS),
      endothelial NOS (eNOS) and brain NOS (bNOS) in the renal tissue of patients with
      IgA nephropathy (IgAN, N = 10), lupus nephritis (LN, N = 5), membranous
      nephropathy (MN, N = 5) and minimal change nephrotic syndrome (MCNS, N = 5).
      Sections were immunostained and the correlation between the expression of each
      NOS and the degree of glomerular injury in that section was also examined. Normal
      portions of surgically resected kidneys served as controls. eNOS was present in
      glomerular endothelial cells and endothelium of cortical vessels in the control
      and diseased kidneys. iNOS was localized in mesangial cells, glomerular
      epithelial cells and infiltrating cells in the diseased glomeruli, whereas
      immunostaining for iNOS was hardly detected in control kidneys. In addition, the
      expression pattern of eNOS in each glomerulus was the reverse of that of iNOS. In
      IgAN and LN, the extent of staining for eNOS correlated negatively with the
      degree of glomerular injury, while the extent of staining for iNOS correlated
      positively with the degree of glomerular injury in the same tissues. bNOS was not
      detected in normal or nephritic glomeruli. Our results indicate the presence of a
      NO pathway in human diseased kidney, and suggest that NO derived from eNOS and
      iNOS may be involved in the progression of renal diseases and that NO derived
      from each NOS may play an important role in different way in human inflamed
      glomeruli.

PMID- 9607211
TI  - Predictors of GBV-C infection among patients referred for renal transplantation.
AB  - The etiology of liver disease remains unknown in about 4 to 23% of dialysis
      patients and 10 to 16% of renal transplant recipients. A search for other
      causative agents of liver disease led to the discovery of the GB group of
      viruses. We studied the association between the presence of GB virus C (GBV-C)
      infection, known risk factors for parenterally-transmitted infections and history
      or laboratory evidence of liver disease among end-stage renal disease (ESRD)
      patients referred for renal transplantation to the New England Organ Bank, MA.
      Stored sera from patients on the renal transplantation waiting list between
      November 1986 and June 1990 were tested for antibody to hepatitis C virus (HCV).
      Sera were available in 1544 of 3243 (48%) patients, and anti-HCV was detected by
      ELISA3 in 287 (19%). All 287 anti-HCV positive patients formed the anti-HCV
      positive cohort and 286 randomly selected anti-HCV negative patients formed the
      anti-HCV negative cohort (573 patients overall). Additional sera were available
      for GBV-C RNA testing in 465 of 573 (81%) patients, and GBV-C RNA was detected by
      RT-PCR in 146. The overall extrapolated prevalence of serum GBV-C RNA was 29%.
      The prevalence of serum GBV-C RNa among anti-HCV positive patients (35%) was not
      significantly different from that among anti-HCV negative patients (29%; P =
      0.22). In a univariate analysis, compared to patients without GBV-C RNA, patients
      with serum GBV-C RNA were younger [odds ratio (OR) 0.98 per year of age, P =
      0.01], had a lower proportion of males (OR 0.64, P = 0.03), lower proportion of
      patients with diabetes mellitus (OR 0.44, P = 0.01), higher proportion of
      patients with a previous transplantation (OR 1.53, P = 0.04), longer duration of
      dialysis at the time of enrollment (OR 1.004 per month on dialysis, P = 0.03),
      and a higher proportion of patients with history of transfusions (OR 4.58, P =
      0.01). Serum GBV-C RNA was not associated with a significantly increased OR for
      history of liver disease or non-A, non-B hepatitis, or elevated serum alanine
      aminotransferase levels. In a step-wise multivariate regression analysis, a
      younger age (OR 0.98 per year of age, P = 0.03), and history of blood
      transfusions (OR 3.89, P = 0.03) were associated with an increased OR for serum
      GBV-C RNA, while diabetes mellitus was associated with a decreased OR for GBV-C
      RNA (OR 0.47, P = 0.01). Anti-HCV was not a predictor of serum GBV-C RNA (OR
      1.07, P = 0.77). The results of this study support the fact that GBV-C is a
      parenterally transmitted virus and shed light on the modes of transmission of GBV
      C among ESRD patients. However, the association with liver disease remains to be
      established.

PMID- 9607212
TI  - Major determinants of hyperhomocysteinemia in peritoneal dialysis patients.
AB  - The mechanisms leading to elevated total homocysteine concentrations in
      peritoneal dialysis patients are only partially understood. We show that a common
      polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene (C677T
      transition) results in increased total homocysteine levels in peritoneal dialysis
      patients compared to age- and sex-matched healthy individuals. The allelic
      frequency of the C677T transition in the MTHFR gene in peritoneal dialysis
      patients (0.29) was comparable to the frequency in healthy individuals (0.34).
      Separate comparison of the total homocysteine plasma levels between non-carriers
      of the MTHFR polymorphism (C/C), heterozygous (C/T) and homozygous (T/T) subjects
      was performed by analysis of covariance in the patient and the control group. In
      the patient group the mean total homocysteine level was 61.7 +/- 40.1 mumol/liter
      in individuals with the (T/T) genotype, which was significantly higher than the
      total homocysteine concentration of 23.1 +/- 15.8 mumol/liter in (C/T) patients
      and 22.2 +/- 11.1 mumol/liter for non-carriers (P = 0.0001). Vitamin B12 (P =
      0.0001), folate (P = 0.0005), serum creatinine (P = 0.016), albumin (P = 0.0157)
      and dialysis center (P = 0.0173) significantly influenced total homocysteine
      plasma levels in peritoneal dialysis patients, whereas this was not the case for
      age, gender, weekly Kt/V, weekly creatinine clearance, residual renal function,
      duration of dialysis, mode of peritoneal dialysis and vitamin intake. Folate
      levels in peritoneal dialysis patients were significantly affected by the MTHFR
      genotype (P = 0.016). Elevated total homocysteine levels in diabetic patients
      with cardiovascular disease were associated with increased cardiovascular
      morbidity. In summary, the present study provides evidence that homozygosity for
      the C677T transition in the MTHFR gene, low vitamin B12 and low folate levels
      result in elevated total homocysteine levels in peritoneal dialysis patients.

PMID- 9607213
TI  - Perfusion quantitation in transplanted rat kidney by MRI with arterial spin
      labeling.
AB  - The purpose of this study was to determine the feasibility of using quantitative
      magnetic resonance imaging (MRI) with non-invasive arterial spin labeling to
      assess perfusion of transplanted kidneys in rats. MRI studies were performed on
      five groups of rats: normal Fisher 344 rats, Fisher 344 rats that had received a
      syngeneic kidney transplant either 3 or seven days prior to study, and Fisher 344
      rats that had received an allogeneic kidney (ACI rat as the donor) either three
      or seven days prior to study. The contralateral native kidney remained in place
      for comparison. Cortical perfusion was quantitated from a slice through the
      center of each kidney in anesthetized rats at 4.7 Tesla with a fast gradient-echo
      MRI sequence following the arterial spin labeling. The spin-lattice relaxation
      time was measured within the cortex, and the cross sectional area of the kidney
      was also determined within the same MRI plane. Immediately after the perfusion
      imaging measurement, transplanted kidneys were removed and scored for rejection
      using the Banff histological criteria. Renal cortical perfusion in normal kidneys
      was 7.5 +/- 0.8 ml/g/min (N = 12 rats, 24 kidneys). At the third day post
      transplantation, that is, before marked acute rejection, the renal cortical
      perfusion rate was similar in both syngeneic and allogeneic kidneys [3.3 +/- 1.7
      (N = 6) and 3.0 +/- 2.4 ml/g/min (N = 6), respectively]. In contrast, at the
      seventh day post-transplantation, that is, during severe rejection, the renal
      cortical perfusion rate in allogeneic kidneys was very low (undetectable)
      compared to the value in syngeneic kidneys [that is, < or = 0.3 (N = 6) versus
      5.2 +/- 2.0 ml/g/min (N = 6), respectively]. Moreover, the renal cortical
      perfusion rate determined by MRI was significantly (P < 0.05, r = -0.82)
      correlated with histological rejection. We conclude that the quantitative
      measurement of renal cortical perfusion by MRI with arterial spin-labeling could
      provide a non-invasive diagnostic method for monitoring the status of renal
      transplants without requiring the administration of a contrast agent.

PMID- 9607214
TI  - Treatment of infected tunneled venous access hemodialysis catheters with
      guidewire exchange.
AB  - Cuffed venous access catheters have become commonplace for hemodialysis access.
      The major complications of these catheters are catheter thrombosis, catheter
      fibrin sheathing and infection. When catheter associated bacteremia occurs
      treatment with antimicrobial therapy alone has been unsuccessful in providing
      acceptable cure rates. Failed antimicrobial therapy exposes the patient to the
      risks of prolonged bacteremia, while the alternative, catheter replacement at a
      new site can lead to central venous stenosis and compromise future long-term
      upper extremity access. Catheter guidewire exchange when the tunnel tract is
      clinically not infected theoretically allows the preservation of future access
      sites and yields a higher treatment success rate while avoiding temporary non
      cuffed access placement. We report a series of 23 cases of hemodialysis patients
      with tunneled cuffed catheters and bacteremia related to the catheter who were
      treated with the exchange of a new catheter over a guidewire combined with three
      weeks of systemic antibiotics. Patients eligible for the study required no
      evidence of tunnel tract infection and defervescence within 48 hours of
      antimicrobial therapy. Technique failure was defined as repeat infection from any
      organism within 90 days of catheter exchange. Four patients (18%) redeveloped
      bacteremia within 90 days of the exchange. The bacteremias developed at 4, 19, 63
      and at 74 days days after the exchange. Guidewire exchange in combination with
      intravenous antibiotics in cases of catheter related bacteremia has an acceptable
      rate of treatment success and is a viable treatment option in a carefully
      selected patient population.

PMID- 9607215
TI  - Effects of balloon angioplasty and stent implantation on intrarenal echo-Doppler
      velocimetric indices.
AB  - This study was aimed at examining whether four intrarenal echo-Doppler
      velocimetric indices (pulsatility and resistive indices, acceleration and
      acceleration time) can be useful for assessing the effects of renal artery
      dilation obtained with either angioplasty or stent implantation. Echo-Doppler
      studies were performed in 63 hypertensive patients with 68 renal artery stenoses
      (39 atherosclerotic and 29 fibromuscular) prior to and within five days after the
      dilation procedures (55 angioplasties, 13 stent implantations), which resulted in
      an average reduction of arterial narrowing from 79% to 20%. In 24 patients, the
      velocimetric indices were also examined in relationship to the venoarterial
      differences of plasma renin activity and of angiotensin II across the stenotic
      kidneys. We found that after dilation the values of the four indices had returned
      within the normal range in all but three arteries (one false negative for
      resistive index and two for acceleration time). However, decrements in
      acceleration time was the only factor to be significantly correlated with the
      reduction of arterial narrowing. Moreover, postdilation values of this index
      were, on average, slightly but significantly higher in arteries that at follow-up
      developed restenosis rather than in those that remained patent. For similar
      reductions in arterial narrowing the absolute changes of all indices were similar
      in atherosclerotic and fibromuscular stenotic arteries and, in a subset of the
      atheromatous arteries, were also similar after angioplasty and stent
      implantation. No relationship was found with the changes in the venoarterial
      differences of plasma renin activity and angiotensin II. It appears that these
      intrarenal velocimetric indices and, in particular, acceleration time reliably
      reflect the technical success of renal artery dilation. The acceleration time
      index may also be valuable for predicting the restenosis of the dilated vessel.
      None of the indices, however, mirrors the functional consequences of removal of
      renal artery stenosis as expressed through the changes in transrenal gradients of
      the components of the renin-angiotensin system.

PMID- 9607216
TI  - RNA metabolism in uremic patients: accumulation of modified ribonucleosides in
      uremic serum. Technical note.
AB  - To determine the metabolism of ribonucleic acid (RNA) in uremia, serum and urine
      levels of ribonucleosides in uremic patients were analyzed using reversed-phase
      high-performance liquid chromatography. The serum levels of xanthosine and all
      modified ribonucleosides were increased in undialyzed patients with chronic renal
      failure (CRF), and patients undergoing hemodialysis (HD) and continuous
      ambulatory peritoneal dialysis (CAPD). The serum level of pseudouridine was
      markedly increased in all the uremic patients especially CAPD patients (32 times
      higher than normal). By contrast, the serum level of adenosine did not show any
      significant change in the uremic patients. Interestingly, the serum and urine
      levels of inosine were significantly decreased in all the uremic patients,
      suggesting that the production of inosine is decreased in uremic patients. The
      serum level of uridine was significantly elevated only in the HD patients. The
      serum levels of all ribonucleosides except inosine and uridine decreased
      significantly after HD. The urinary excretion of inosine, 1-methyladenosine, 1
      methylguanosine, N2,N2-dimethylguanosine and N4-acetylcytidine was significantly
      decreased in the CRF patients, leading to the accumulation of these modified
      ribonucleosides in the uremic serum. CAPD patients showed markedly increased
      serum levels of modified ribonucleosides such as pseudouridine, 1-methylinosine,
      and N2,N2-dimethylguanosine and N4-acetylcytidine as compared with the HD
      patients. These results demonstrate that there was an altered metabolism of RNA
      in uremic patients with marked accumulation of modified ribonucleosides.

PMID- 9607217
TI  - Chemokines in interstitial injury.

PMID- 9607218
TI  - GB virus-C (hepatitis G virus) nostalgia.

PMID- 9607219
TI  - Endothelial cell activation.

PMID- 9607220
TI  - [Neuroendocrine carcinoma of the larynx. Review of literature in reference to one
      case report].
AB  - Neuroendocrin tumors are unusual neoplasies, even more within the ENT-sphere.
      Report of 1 case treated in our Service. Review of immunohistochemical criteria
      with the aim of achieving the diagnosis. Some bibliographical series are analyzed
      with the target to pick up the treatment of these uncommon growths.

PMID- 9607221
TI  - [Aspergillosis of the paranasal sinuses].
AB  - Because of the shortage of rhinosinusal aspergillosis cases, as the reported
      here, we think this article might be of interest. The lesion, localized in
      maxillary sinus, triggered a reactive pansinusitis, afebrile and void of general
      impact. Description of our way to attend the case, the procedure to achieve the
      diagnosis and differential diagnosis as well. Bibliographical references.

PMID- 9607222
TI  - [An auricular pseudocyst. A report of 4 cases].
AB  - The words pseudocyst of the pinna was suggested in 1966 by Engel for those
      intracartilaginous swellings of the auricula, presenting in young healthy males
      without traumatic precedents or previous manipulation. The AA. report 4 cases
      diagnosed and treated in their Hospital Department. A woman, 85, was one of them.
      Review of the subject's literature.

PMID- 9607223
TI  - [Cervical metastasis of choriocarcinoma].
AB  - Neck metastatic adenopathy involves to set off a protocol aiming to specify the
      growth's origin. Complete ENT-examination facing a hard, movable, laterocervical
      lump is compulsory. Lacking the primary next comes fine needle biopsy and if it's
      not clear enough a cervicotomy must be performed. We report the diagnosis, the
      treatment and the follow-up of a testicle choriocarcinoma case, diagnosed through
      neck biopsy. Perusal of the bibliography.

PMID- 9607224
TI  - [Osteomas of frontal-ethmoid sinuses].

PMID- 9607225
TI  - [Concomitant hyperfractionation of drugs and irradiation in the treatment of
      advanced ENT cancers].
AB  - Considering the limited results achieved up to now in the treatment of advanced
      ENT-cancer, with the classic customary procedures, the AA. suggest a new
      therapeutic schedule (within the concurrent radio-chemotherapy context) in which
      the selected cytotoxic drug, the carboplatin, is a part of each therapeutic
      fraction. A group of 36 patients suffering advanced ENT-cancer (2 cases stage III
      and 34 stage IV) were studied between Mars 1993 and September 1995, and the
      outcomes assessed after a 18 months mean follow-up (30 months maximum). There
      were 11% surgically rescued cases, being the full dosage administered twice daily
      8.050 cGy plus 700 mg carboplatin. Tolerance was very good, so 100% of the
      patients received a complete treatment. Initial response was also fine resulting
      93% full remissions on primaries, 96% on neck adenopathies (6% surgical rescues).
      Regarding the actuarial control after 30 months were controlled 88% of neck
      adenopathies, control loco-regional amounted for 69%, control on primaries 63%
      and actuarial survival amounted 55%. The AA. drawn out 10 conclusions,
      underlining the good tolerance of the therapeutic sketch proposed, because the
      antineoplastic results are by far better than those experienced with whichever
      modality of management of tumors of these sites and staging.

PMID- 9607226
TI  - [Eosinophilic ulcers of the tongue as an adverse reaction to carbamazepine].
AB  - We describe a typical case of eosinophilic ulcer of the oral mucosa (EUOM) after
      an adverse reaction to carbamazepine, in a manic-depressive patient. This case
      may be suggestive of other etiologic factors for the EUOM, different to traumas.

PMID- 9607227
TI  - [Congenital cervical deformities].
AB  - The paper deals with the survey of 66 congenital neck malformations (27
      thyroglossal cysts and 32 branchial plus 7 lymphatic anomalies) surgically
      treated in the last 5 years term. Thyroglossal cysts presented in children and
      young people, in the middle line, and 92.6% of them were infrahyoid. Recidivation
      appeared in 7.4% of all cases, always in connection with previous infections.
      Branchial malformations presented on the neck's side of middle age persons were
      related to the 2nd. cleft (97%). Lymphatic anomalies presented in children under
      3 years, in these instances the dissection sheaths were not spared and the
      neighboring structures altered.

PMID- 9607228
TI  - [Tracheobronchial foreign body in the laryngectomized patient].
AB  - We report a case of aspiration of a foreign body in the left tracheobronchial
      tree occurring in a laryngectomy, operated one year previously. The accident
      presented by fracture of the inner tracheostomy cannula. The literature is
      reviewed in order to explain possible causes of tracheostomy tube components
      breakage and to suggest methods for preventing such complications.

PMID- 9607229
TI  - [Spanish Society of Family and Community Medicine and continuing education of
      family physicians].

PMID- 9607230
TI  - [Efficacy of a training technique concerning clinical interview skills associated
      with psychodiagnostic ability of the physician].
AB  - OBJECTIVE: To evaluate the efficacy of a training technique to improve clinical
      interview skills connected with Primary Care doctors' psycho-diagnostic ability:
      visual contact, posture, verbal and non-verbal ways of advancing the interview,
      verbal interruptions and questions with a psychological content. DESIGN: The
      doctors were randomly divided into two groups. A before-and-after design with
      blind evaluations was used. SETTING: University postgraduate Internal Medicine
      Course. MATERIAL: 20 doctors. INTERVENTIONS: Step-by-step training with feedback,
      using role-play and video-recording (experimental) was compared with a self
      administered teaching programme (self-training). MEASUREMENTS AND RESULTS: Skills
      were measured by video-recordings of a patient interview one month before and one
      month after the intervention. The Observation Scale of Doctor's Skills was used.
      In the second evaluation, the experimental group differed from the self-training
      group in visual contact, posture and non-verbal ways of advancing the interview.
      CONCLUSIONS: The efficacy of a training technique in improving non-verbal active
      listening skills was shown. It was valuable as a support to the psycho-diagnostic
      ability of the doctor.

PMID- 9607231
TI  - [Analysis of emergency referrals to dermatology].
AB  - OBJECTIVE: To analyse the urgent consultations sent by doctors to a Dermatology
      Department for origin, reason for referral, clinical compliance, suspected
      diagnosis, concordance with the dermatologist's diagnosis and justification of
      the urgent referral. DESIGN: Descriptive study. SETTING: The information was
      gathered in the tertiary specialist Dermatology service of Navarra, which covers
      the whole population. PARTICIPANTS: Of the total (595) number of urgent forms
      received by the service in 1995, 505 were analysed and contrasted with the
      dermatological clinical history. Each patient corresponded to a form.
      MEASUREMENTS AND MAIN RESULTS: The following was analysed: age, sex, origin of
      referral, reason for referral, clinical compliance, suspected diagnosis,
      concordance with the dermatologist's diagnosis and justification of the urgent
      referral. Most letters came from Health Centres (48.5%). The most commonly
      alleged reason for referral was diagnostic help (51.2%). There was good clinical
      compliance only in the notes coming from hospital Casualty Departments (78.7%).
      CONCLUSIONS: There were major deficiencies in all the points under analysis, with
      no significant differences as to origin, except for hospital Casualty, which had
      better clinical compliance and whose referrals were more justified.

PMID- 9607232
TI  - [Health status and morbidity perceived by a group of school children].
AB  - OBJECTIVES: To find what self-perception of their health (SPH) and of their
      morbidity by school-children; and to analyse possible differences, in function of
      their social and demographic characteristics and life-styles. DESIGN: An
      observational crossover study, using a health questionnaire. SETTING: Community.
      PARTICIPANTS: 548 6th and 8th grade (EGB) children in the Occidente Health Area,
      Cordoba. INTERVENTIONS: Self-filled health questionnaire. MEASUREMENTS AND MAIN
      RESULTS: 43.7% of students felt very healthy. Bad SPH was independently
      associated with being a girl, poor state of physical fitness and feeling unhappy.
      Tiredness and nervousness were the most frequent disorders suffered by school
      children. CONCLUSIONS: Although the SPH of the school-children was acceptable, we
      found high perceived morbidity and prevalence of accidents, along with a striking
      consumption of medication.

PMID- 9607233
TI  - [Effects of the professional profile of family and community medicine tutors on
      residents' training].
AB  - OBJECTIVE: To determine what variables concerning tutors are associated with the
      results of the evaluations of their third-year residents. DESIGN: Crossover
      observational study. SETTING: All the teaching health centres in the province of
      Valencia in 1994. PARTICIPANTS: All the tutors and third-year residents, 78
      people in all. MEASUREMENTS AND RESULTS: The information was gathered by original
      questionnaires, previously validated and capable of contrasting the same
      information. There was high tutor-resident concordance (0.51-0.65) for teaching
      activities, supervision of the resident and integration in the Primary Care team
      (IPCT). There was excellent concordance (0.64-0.92) between residents and tutors
      for sessions and the resident's research. The variables which differentiated
      tutors and residents were, according to the ANOVA, Kruskal-Wallis and Chi-squared
      tests: clinical demand, sessions, number of scientific journals read, number of
      sessions supervising residents, satisfaction with the resident and IPCT. With the
      agglomerative iterative method in cluster analysis, four groups of residents were
      formed, with the significant variables (p < 0.05). CONCLUSIONS: IPCT and clinical
      activity were the variables which most differentiated tutors from groups of
      residents.

PMID- 9607234
TI  - [Mortality due to HIV/AIDS infection in the Community of Castile and Leon].
AB  - OBJECTIVE: To find the effect of HIV/AIDS infection on mortality and its
      evolution between 1989 and 1993. DESIGN: Descriptive epidemiological study.
      SETTING: Mortality study in the Community of Castilla y Leon. PATIENTS AND OTHER
      PARTICIPANTS: The source of information used were the vital statistics published
      by the National Institute of Statistics. Mortality was analysed for the principal
      causes of death in people aged between 15 and 54. Specific and standardised
      mortality rates were calculated in function of the variables, year of death, age
      and sex. MEASUREMENTS AND MAIN RESULTS: Mortality due to HIV/AIDS infection
      increased progressively over time in both sexes, reaching in 1993 a rate of 13.56
      per 10(5) in males and 3.52 per 10(5) in women. In 25 to 34-year old women the
      main causes of death were HIV/AIDS infection (9.36 per 10(5)) and traffic
      accidents (3.94 per 10(5)), whereas in men they were traffic accidents (38.67 per
      10(5)) and HIV/AIDS infection (26.88 per 10(5)). CONCLUSIONS: Mortality due to
      HIV/AIDS has increased in recent years and at present is the main cause of death
      in 25 to 34-year old women, and the second in men of this age-group.

PMID- 9607235
TI  - [The magnitude of fatness: prevalence and type of obesity in people registered at
      a health center].
AB  - OBJECTIVE: To determine prevalence and type of obesity; and, secondarily, to
      determine the prevalence of factors of cardiovascular risk in obese patients.
      DESIGN: Descriptive observational study. SETTING: Catchment area of an urban
      Health Centre. PARTICIPANTS: People over 14 and of both sexes registered at the
      Health Centre. INTERVENTIONS: 270 people were contacted, of whom 191 (70.7%) were
      finally studied for weight, size and Quetelet index. When this index was 25 or
      over, the waist/hip index was studied. RESULTS: The prevalence of obesity for the
      whole population registered at the Health Centre was 13.5% (15.4% in men, 12.1%
      in women). Prevalence increased with age, and was highest for both sexes in the
      65-74 age-group (28%). The type of obesity prevalence has resulted 84.6% for
      android type and 15.3% for gynecoid. CONCLUSIONS: Obesity is a first-order
      problem, not only because of its high prevalence and the greater frequency of the
      male type, but because of the high prevalence of cardiovascular risk factors in
      obese people.

PMID- 9607236
TI  - [Analysis of opinions, attitudes and knowledge of physicians of health centers of
      Valencia concerning efficacy and efficiency of drug prescriptions].
AB  - OBJECTIVE: To find the views, attitudes and knowledge of Primary Care doctors
      concerning the efficacy and efficiency of medical prescription. DESIGN:
      Descriptive, crossover study. SETTING: 10 Health Centres in the city of Valencia.
      PARTICIPANTS: The 115 doctors, both general and family practitioners, working at
      these centres. INTERVENTIONS: A survey gathered information on the doctors' views
      about the appropriateness of considering price when prescribing, on their
      assessment of ten strategies aimed at improving prescription efficiency, and
      their understanding of the efficacy and cost of certain medicines used in Primary
      Care. RESULTS: 1. 81% of those surveyed stated that prescription costs had to be
      considered at the moment of deciding patient treatment. 2. 70.4% of their
      opinions of the efficacy of medicines, as measured by the Intrinsic Therapeutic
      Value, were accurate. 3. 41% of the prices estimated by doctors were correct.
      There was a tendency to undervalue prices and to eliminate differences between
      products of identical composition. 4. In the area of strategies to improve
      prescription efficiency, doctors clearly favoured training strategies
      (prescription guidelines or in-work training) over strategies involving "assuming
      economic risks" (pharmacy self-management...).

PMID- 9607237
TI  - [The use of hypothesis in scientific research].

PMID- 9607238
TI  - [Ecstasy: a forgotten drug].

PMID- 9607239
TI  - [The family physician and designer drugs].

PMID- 9607240
TI  - [Let's make the most of tetanus vaccination].

PMID- 9607242
TI  - [Bilateral tendinitis caused by ciprofloxacin].

PMID- 9607241
TI  - [Complications of sinusitis].

PMID- 9607243
TI  - [Should hospitals compete against, dominate or share with primary care?].

PMID- 9607244
TI  - [Controversies concerning oral anticoagulation control in primary care].

PMID- 9607245
TI  - [Evaluation of the effectiveness of metabolic self-control through direct
      dispensation of diagnostic strips to type 2 diabetic patients].
AB  - OBJECTIVE: To perform an evaluation of the effectiveness of diagnostic strips in
      metabolic control by type 2 diabetics. DESIGN: A crossover, observational study.
      SETTING: Primary Health Care. PATIENTS: A sample of 400 histories at a Primary
      Care Centre (PCC), representative of Diabetes 2 patients who used reactive strips
      directly dispensed at PCCs as a method of home self-analysis of their disease,
      was evaluated. They were monitored in 1995 and 1996 in the seven health districts
      in the Primary Care region of Tortosa. MEASUREMENTS AND MAIN RESULTS: The use of
      reactive strips was considered effective if the data recorded in the PCC
      histories satisfied the criteria for acceptable metabolic control, as defined by
      the GEDAPS, for the previous year of monitoring, or for at least three months if
      the period of use of the strips was under a year. Mean annual cost and
      consumption per diabetic, and the evolution of these over the study period, were
      calculated. CONCLUSIONS: Direct dispensing of reactive strips led to an important
      annual increase in cost (+46.59%) and consumption (+89.25%), but acceptable
      effectiveness was not demonstrated (1.10%).

PMID- 9607246
TI  - [Trial of the efficacy of health education programs on therapeutic compliance in
      arterial hypertension].
AB  - OBJECTIVE: To analyse by means of a group session and postal support the efficacy
      of health education (HE) on compliance with therapy for light-to-moderate
      essential Hypertension. DESIGN: Controlled clinical trial with randomised
      distribution. SETTING: Primary Care. PATIENTS: 110 hypertense patients with new
      or uncontrolled Hypertension, for whom treatment with Trandolapril as a start or
      change of medication was indicated. INTERVENTIONS: The patients were split into
      two groups at random, with observation for six months after inclusion in the
      study and monthly attendance: 1) Control group (CG) of 55 patients who received
      HE from their family doctor; 2) Intervention group (IG) of 55 patients
      controlled. MEASUREMENTS AND RESULTS: Patients were defined as compliant if their
      consumption was 80-110% of what was prescribed. The counting of pills was
      recorded. Percentages of compliant patients and mean compliance were analysed
      with the Chi squared and Student's t tests. 109 people completed, 77 of them
      women. Neither group differed as to age, sex, length of evolution, number of
      diseases or doses of drugs consumed. CONCLUSIONS: Intervening in HE with a group
      session and postal follow-up is an efficacious measure to improve therapeutic
      compliance in Hypertension cases.

PMID- 9607247
TI  - [Prevalence of obesity and its relationship with cardiovascular risk in the
      general population of Albacete].
AB  - OBJECTIVE: To find the prevalence of obesity and overweight in the population of
      Albacete, and their relationship to other cardiovascular and coronary risk
      factors. DESIGN: A descriptive, crossover population study. SETTING: Community
      setting in the province of Albacete. PARTICIPANTS: A sample of 2121 people over
      18 (843 from the capital and 1278 from the rest of the province) was selected
      from Albacete's population through stratified random sampling in two stages.
      MEASUREMENTS AND RESULTS: Appointments were made with each person by mail. All
      those attending underwent Anamnesis, a physical examination, ECG and basic
      analytic tests. 1230 people between 20 and 93 years old were studied. 394 were
      considered not obese (32%) and 836 were adjudged obese or overweight (68%). 47%
      of men were overweight and 23.2% of them obese; 33.5% of women were overweight
      and 32.5% obese. CONCLUSIONS: Obesity is a highly prevalent pathology in this
      province and increases with age. Overweight is more common among men and obesity
      among women. Hypertension, Hyperlipaemia, Diabetes and high Fibrinogen are more
      prevalent in obese than in non-obese patients and increase in prevalence along
      with the obesity. Patients with the risk factors under study are generally obese.
      The coronary risk calculated was higher among the obese, the risk increasing
      along with excess of weight.

PMID- 9607248
TI  - [Dependence on self-care and walking of the aged in a rural community].
AB  - OBJECTIVE: To evaluate the dependence on 5 basic daily activities (BDA) and on
      walking, and their relationship to the frequency of attendance at the family
      doctor. DESIGN: A crossover study using a home survey of health. SETTING: Town of
      Villanueva de los Castillejos in Huelva. PARTICIPANTS: Those 65 or over.
      INTERVENTIONS: The dichotomous form of the Katz Index, with the incontinence item
      excluded (scores from 0-5), was used. Walking was assessed by the Functional
      Walking Categories (FWC) of Massachusetts General Hospital. RESULTS: Information
      on 139 men and 231 women was obtained (85.6% of the actual population). 15.3%
      (95% CI, 11.3-19.0), 12.4% of the men and 16.9% of the women (p > 0.05), stated
      their dependence in one or more BDA. 22.5% of the population (95% CI, 18.2-26.8),
      8.9% of the men and 30.6% (p = 0.001) of the women, said they found it difficult
      to walk. CONCLUSIONS: There is a high rate of dependence in the population group.
      Light dependence is associated with more frequent medical consultations than
      either independence or severe dependence.

PMID- 9607249
TI  - [The genogram in the evaluation of natural family vital cycle and its
      dislocations].
AB  - OBJECTIVES: To evaluate whether the reading of the genogram allows the stages of
      the family vital cycle (FVC) and the map of relationships to be identified; and
      to study how it can be used to find the FVC and its dislocations, and family
      relationships. DESIGN: Descriptive crossover study. SETTING: Primary Care. Health
      Centres at Almanjayar and Cartuja (Granada). Patients and other participants. 499
      genograms performed and analysed by Primary Care doctors. INTERVENTIONS: Reading
      of the genograms by two doctors who had not participated in taking them, to
      establish whether the FVC stages and the map of relationships could be
      identified, and the cycle and its dislocations classified. RESULTS: The reading
      of the genogram enabled the stages of the FVC to be identified in 96% of cases.
      66% of the genograms had the map of relationships correctly drawn. We found that
      30% of families were at the fourth stage, 22% in II-B and 19% in II-A. 43% of the
      genograms contributed data on family relationships. Dislocations in the FVC were
      evident in 16.6%. CONCLUSIONS: When the genogram is well-constructed, we consider
      it a good tool for classifying families into the appropriate stage of the FVC,
      evaluating the role of family interactions throughout the cycle and discovering
      disruptions in the FVC.

PMID- 9607250
TI  - [Prevalence of xerostomia in the general population].
AB  - OBJECTIVE: Principally, to establish the prevalence of xerostomia in the general
      population and, second, to find the association of xerostomia with the
      consumption of tranquillizers and anti-depression, anti-allergy, anti
      Hypertension and hypnotic drugs. DESIGN: A crossover study of prevalence.
      SETTING: The urban area of Sant Joan Despi, Barcelona. PARTICIPANTS: Random
      sample, stratified by age and gender (268 people). MEASUREMENTS AND MAIN RESULTS:
      A telephone survey on xerostomia and drugs intake was conducted. Prevalence in
      the population of xerostomia was 9.7%. There was a linear relationship between
      being older and greater prevalence of xerostomia. The differences found for
      gender was not significant. There was an association between xerostomia and
      intake of the aforesaid drugs. CONCLUSIONS: The high prevalence of xerostomia and
      its association with commonly used drugs should arouse doctors to seek adequate
      solutions.

PMID- 9607251
TI  - [Prevalence of hepatitis C virus infection and cohabiting contacts].
AB  - OBJECTIVES: Study of the prevalence of Hepatitis C infection and of cohabiting
      contacts. DESIGN: A descriptive crossover study. SETTING: Health District.
      PATIENTS: There were a total of 13,500 people with histories opened at our
      centre. The histories of patients attending for general medical consultations
      between January 1995 and December 1996 were reviewed for Ac+ to the Hepatitis C
      (HC) virus. RESULTS: 145 patients were found to be Ac positive for HC (1.07%; CI,
      0.9-1.2). 135 were index cases and 10 contacts. The most important items of
      history were intravenous drug use in 33 carriers (23%), transfusion in 22 (15%),
      contact with non-disposable material in 97 (67%) and surgery in 119 (82%). 115
      (79%) of those infected had Transaminase disorder (< x10). CONCLUSIONS: The 1.07%
      prevalence found was similar to other studies. Previous surgery stood out among
      the factors causing risk of infection. Prevalence among cohabitants was 7%, half
      through sexual contacts. Since there was a higher prevalence of HC+ among family
      members (50% sexual partners), we believe the study should be extended and
      followed up in the family environment.

PMID- 9607252
TI  - [Cervical cancer screening: whom and when].

PMID- 9607253
TI  - [Usefulness of fixed-dose drug combinations].

PMID- 9607254
TI  - [Subclinical thyroid dysfunction in primary care].

PMID- 9607255
TI  - [Antibiotic treatment of otitis media in children].

PMID- 9607256
TI  - [Eruption of purpura compatible with vasculitis and torasemide].

PMID- 9607257
TI  - [Detection of a possible cognitive change: mini-mental or Pfeiffer?].

PMID- 9607258
TI  - Folk belief, illness behavior and mental health in Taiwan.
AB  - In this paper, an overview of the literature relevant to the issues of illness
      behavior and help-seeking behavior in relation to mental health and illness,
      focusing on the Taiwan area is presented. Arguments for the prioritization and
      appreciation of the folk perspective of mental illness and health are addressed.
      The traditional medical beliefs in the Chinese culture that emphasize integration
      and continuity, instead of differentiation, of/between body and mind, person and
      nature, nature and super-nature, the visible (with form) and the invisible
      (without form), and yang and yin, have laid the basis for the theoretical
      framework of somatization as normative illness behavior rather than
      psychologization, and also dissociation as normative illness behavior rather than
      repression. A case report on folk psychotherapy is given here to illustrate the
      argument. The continuum models illustrated in this paper, either the shen-kuei
      syndrome in its broad sense extending from koro to neurasthenia, frigophobia or
      the spirit possession syndrome in its broad sense extending from the pathological
      and peripheral (Hsieh-ping) to the normative and ritual (shamanism), could well
      remind us of the powerful influence of the folk and popular contexts of culture
      that underlie illness behavior in relation to mental health in Taiwan.

PMID- 9607259
TI  - Photodynamic therapy for facial squamous cell carcinoma in cats using Photofrin.
AB  - BACKGROUND: Photodynamic therapy (PDT) has been shown to be an effective
      treatment modality for surface-oriented neoplasms of the skin, respiratory,
      gastrointestinal, and urogenital systems. The purpose of our study was to assess
      the safety and efficacy of PDT using Photofrin in the treatment of squamous cell
      carcinomas of feline facial skin. MATERIALS AND METHODS: Cats with naturally
      occurring squamous cell carcinomas of the skin were entered into the study. PDT
      was delivered to the tumors using an argon-pumped dye laser 48 hours after the
      administration of the photosensitizer porfimer sodium (Photofrin). Following
      treatment, the tumors were evaluated for complete response rates and local
      control durations. RESULTS: Eight tumors were staged T1a, 9 staged T1b, and 14
      staged T2b. Complete response rates as well as local control durations were
      significantly related to stage (p < 0.0001). Complete response was achieved in
      100% of the T1a tumors and 53% of the T1b tumors; the overall 1-year local
      control rate for all treated tumors was 62%. Clinical, hematological, and
      biochemical evidence of toxicity was not seen in any cat following drug
      administration. CONCLUSION: PDT with the photosensitizer Photofrin was safe and
      effective in treating early stage squamous cell carcinomas of the feline skin.

PMID- 9607260
TI  - Effects of silicon-insole socks on pressure distribution and shear force of the
      foot.
AB  - BACKGROUND: Many problems of the foot are due to abnormal plantar pressure and
      shear force, but until now shear force could not be accurately measured.
      Different methods can be used to reduce foot pressure, such as foot orthosis or
      shoe modification. The purposes of our study were to propose a method for
      measuring the maximum shear force of the foot and also to investigate the effect
      of silicone-insole socks in reducing the peak plantar pressure and shear stress
      of the foot. METHODS: Twenty-two healthy subjects were included in this study,
      each subject underwent 2 kinds of experiments to study the peak plantar pressure,
      the horizontal shear reaction force, and the maximum shear force under 3
      conditions: barefoot, wearing 100% cotton socks, and wearing silicone-insole
      socks. RESULTS: Our results showed a significant decrease in midfoot peak plantar
      pressure while walking, and a decrease in horizontal shear reaction force and
      maximum shear force while wearing cotton socks and silicone-insole socks in
      walking and pulling. Silicone-insole socks were more significant in decreasing
      horizontal shear reaction force than cotton socks. CONCLUSION: Silicone-insole
      socks are better than cotton socks in reducing horizontal shear reaction forces
      and their friction coefficients. Because only normal subjects have been tested,
      further study is required to prove the efficacy of silicone-insole socks on
      different kinds of foot pathology.

PMID- 9607261
TI  - Once-daily nifedipine sustained release (nifelan) on forearm vascular resistance
      and regression of left ventricular hypertrophy in patients with mild to moderate
      essential hypertension.
AB  - BACKGROUND: Nifelan, a sustained-release formulation of nifedipine, is a new
      antihypertensive agent. However, its effect on peripheral vascular resistance and
      left ventricular mass is still controversial. METHODS: We evaluated the
      antihypertensive efficacy and safety of nifelan in 20 patients with mild to
      moderate essential hypertension. After 2 weeks of a placebo-qualifying phase, the
      eligible patients were entered into an 8-week active treatment period in which
      nifelan was given 10-40 mg once-daily with gradual titration. RESULTS: Seventeen
      patients (8 men, 9 women; age range 43-72 years, mean 52 years) completed the
      entire study. The mean sitting systolic and diastolic blood pressures were
      significantly reduced (p < 0.0001) by 13.8 mmHg and 9.6 mmHg, respectively, with
      a mean nifelan dose of 27.1 +/- 2.7 mg per day, while the heart rate remained
      unchanged (75.9 +/- 1.3 vs. 73.6 +/- 0.9 beats per minute, p = NS). Four patients
      (20%) reported side effects necessitating termination of nifelan treatment in 2
      patients because of intolerance. One patient was found to be poorly compliant and
      withdrew prematurely from the study for unknown reasons without complaints of
      adverse effects. Echocardiographic left ventricular mass index was significantly
      reduced from 104.2 +/- 4.6 g/m2 to 96.6 +/- 5.2 g/m2 (p < 0.05), and the left
      ventricular diastolic function evaluated by E/A ratio showed a trend toward
      improvement from 0.97 +/- 0.06 to 1.10 +/- 0.07 (p = 0.06). Both forearm
      hemodynamic parameters showed favorable changes from baseline to the end of the
      study (forearm blood flow, 3.39 +/- 0.28 vs. 4.04 +/- 0.31 ml/100 ml/min, p <
      0.05; forearm vascular resistance, 37.75 +/- 4.95 vs. 28.73 +/- 3.34 mmHg/ml/100
      ml/min, p < 0.05). The lipid profiles followed trends toward favorable changes
      after treatment (high density lipoprotein, 51.8 +/- 3.0 vs. 54.4 +/- 3.3 mg/dl, p
      = NS; low density lipoprotein, 146.1 +/- 8.8 vs. 139.9 +/- 10.6 mg/dl, p = NS).
      Hematological and biochemical parameters did not change at the end of treatment.
      CONCLUSION: Once-daily nifelan as monotherapy was safe and effective in Chinese
      patients with mild to moderate essential hypertension. Regression of left
      ventricular mass and reversal of unfavorable forearm hemodynamics were observed
      in these patients after short-term therapy.

PMID- 9607262
TI  - Treatment of giant cell tumor of bone: a comparison of local curettage and wide
      resection.
AB  - BACKGROUND: Giant cell tumor of bone is benign but locally aggressive neoplasm
      with a tendency for local recurrence. Although various treatment options have
      been utilized and reported, it remains a difficult therapeutic problem for the
      orthopedic surgeon. METHODS: We reviewed the results of the treatment of giant
      cell tumor of bone in 27 patients. Eleven patients were treated with extended
      curettage and burring then packing with cement, while 16 patients had wide
      resection and reconstruction. RESULTS: At an average of 50 months after surgery,
      the recurrence rate of curettage was 27% and that of wide resection was 6.25%.
      Two of the three patients who had a recurrence after curettage were treated by a
      secondary curettage procedure and were later free of disease. Overall, the local
      control rate after second curettage and packing with cement was 90.9%. There was
      no infection in the curettage group but infection occurred in 3 patients of the
      resection group. Eight patients in the curettage group (80%) had an excellent
      functional result but only 2 patients in the resection group (13%) achieved an
      excellent result. CONCLUSION: This study demonstrates that either curettage and
      packing with cement or wide resection are effective in treatment of giant cell
      tumor of bone. There is, however, a better functional result after curettage and
      packing with cement than following wide resection. We recommend curettage and
      cement packing for giant cell tumor of bone whenever it is technically feasible.

PMID- 9607263
TI  - Foreign bodies in tracheobronchial tree in children: a review of cases over a
      twenty-year period.
AB  - BACKGROUND: Foreign body inhalation into the tracheobronchial tree of children is
      rather rare but serious problem. It may be hazardous and even cause fatal
      sequelae in the children if misdiagnosed and not managed promptly. METHODS: We
      retrospectively reviewed the records of 81 patients with foreign bodies inhaled
      into the larynx, trachea and bronchi. The children were all treated during the 20
      year period from July 1976 through June 1996 at Chang Gung Memorial Hospital. Of
      these patients, 82% were 36 months of age or younger. The male to female ratio
      was 3:1. All of the patients initially received flexible fiberoptic bronchoscopy
      to identify the foreign objects. The foreign bodies were removed by jet
      ventilation bronchoscopy with apneic techniques under general anesthesia.
      RESULTS: Peanuts were found to be the most common causative foreign body agent
      which occurred in 53 instances (65%). The most common manifestation was coughing,
      with subsequent dyspnea and audible wheezing. The foreign bodies were lodged in
      the left bronchus more than in the right. The most obvious radiologic evidence
      observed in aspirated children were emphysematous changes at same side of the
      foreign bodies caused by "expansile check-valve" phenomenon. Four patients showed
      radio-opaque objects on chest roentgenograms. Six patients required second
      extraction procedures due to the retained foreign bodies. Neither serious
      complications nor deaths occurred in these patients due to the foreign body
      inhalation. CONCLUSION: Early diagnosis and management is essential in children
      with foreign bodies in the airways to prevent morbidity or death. Small materials
      or food bits should be kept far away from young child.

PMID- 9607264
TI  - Short-term treatment of obesity with fluoxetine as a supplement to a low calorie
      diet.
AB  - BACKGROUND: Inhibitors of serotonin re-uptake including fluoxetine have generally
      been successful in inducing modest but statistically significant weight
      reductions in clinical trials. However, there are few published trials with
      serotonin re-uptake inhibitors in obesity therapy on Asians. This study aimed to
      assess the effect of fluoxetine as an adjunct therapy to a low calorie diet in
      the obese Taiwanese population. METHODS: Sixty healthy obese subjects [body
      weight > 130% of ideal body weight (IBW)] were instructed to follow a low calorie
      diet. All subjects were randomized to receive fluoxetine 60 mg once daily with
      diet or diet only for 12 weeks. RESULTS: The mean total body weight reduction at
      the end of the study was significantly greater in the fluoxetine group than in
      the diet group (mean +/- S.E., -5.75 +/- 0.69 vs. -3.06 +/- 0.59 kg, p = 0.008).
      The body weight reduction in the first 4 weeks and second 4 weeks were greater in
      the fluoxetine group and they were statistically significant (mean +/- S.E., 1st
      4 weeks: -2.57 +/- 0.34 vs. -1.24 +/- 0.22 kg, p = 0.0033; 2nd 4 weeks: -1.90 +/-
      0.25 vs. -0.9 +/- 0.35 kg, p = 0.0226). In the third 4 weeks, the weight
      reduction in the fluoxetine group was still greater, but it was not statistically
      significantly (mean +/- S.E., third 4 weeks: -1.21 +/- 0.34 vs. -0.73 +/- 0.25
      kg, p = 0.299). More symptoms of anorexia and nausea were noted in the fluoxetine
      group. The other side effects noted in the fluoxetine group were usually mild and
      tolerable. CONCLUSION: Fluoxetine is effective, well tolerated and relatively
      safe in the short-term treatment of obesity in the Taiwanese population when
      added to a low calorie diet.

PMID- 9607265
TI  - Hemoptysis in children.
AB  - BACKGROUND: Hemoptysis is rare in children, yet is one of the most frightening
      manifestations of cardiopulmonary disease. A wide spectrum of diseases has been
      reported to cause hemoptysis in children, but the search for a specific cause can
      be tedious and unrewarding. Early diagnosis and interventions of hemoptysis are
      extremely important for the successful management of this potentially lethal
      process in children. METHODS: From July 1994 to June 1996, 15 pediatric patients
      ranging from 1 month to 15 years of age were admitted to the Pulmonology division
      for the investigation of hemoptysis. We retrospectively reviewed the clinical
      records and diagnostic evaluations of these patients. RESULTS: Six (40%) of the
      patients investigated were infectious in origin, only one patient had tuberculous
      infection. Three patients had a traumatic cause and 2 patients had foreign bodies
      in the airway. Two cases had no obvious contributing cause of hemoptysis despite
      extensive investigations. One patient had hematemesis because bleeding from
      esophageal ulcerations was misinterpreted as hemoptysis. One patient had
      varicosed tracheal and bronchial collaterals causing massive hemoptysis due to
      portal vein obstruction and hypertension. CONCLUSION: Pulmonary infection was the
      leading cause of hemoptysis in the 15 children we studied, but Mycobacterium
      tuberculosis is an uncommon causative agent. Bronchoscopy is an extremely useful
      tool for the diagnosis and localization of hemoptysis. Hematemesis may be
      misinterpreted as hemoptysis, particularly when an accurate history is not
      possible in children, therefore, bleeding from the upper aerodigestive tract
      should be studied meticulously and excluded adequately using endoscopy.

PMID- 9607266
TI  - A quick method to extract DNA from paraffin-embedded tissues.
AB  - BACKGROUND: The amplification power of the polymerase chain reaction (PCR)
      technique has had great impact in molecular analysis, and DNA extraction is a
      common requirement in retrospective studies utilizing PCR as a tool. Conventional
      methods used in deparaffinization, harvesting and purification of DNA from
      paraffin-embedded tissue are time consuming and cause a significant loss in the
      yield of DNA. METHODS: We utilized heating-melting-cooling removal of paraffin,
      digestion of the sample with proteinase K and purification of the extracted DNA
      by a microconcentrator. The products, after PCR amplification of the p53 gene
      exon 8, were used to make a comparison between our method and the conventional
      xylene-phenol-choloform method. RESULTS: The amplified products from our method
      were superior to that of the conventional method. CONCLUSION: The method we
      propose has a better recovery of DNA and is more time efficient.

PMID- 9607267
TI  - Pregnancy after orthotopic liver transplantation in a Chinese patient: a case
      report.
AB  - A 28-year-old woman who had undergone orthotopic liver transplantation due to
      decompensated liver cirrhosis conceived 2 years after the operation.
      Immunosuppressive treatment was maintained during the pregnancy. The case was
      managed as high risk. Although intrauterine growth retardation arose in the third
      trimester, the patient finally gave birth to a healthy male baby. To our
      knowledge, the present case is the first successful pregnancy of an Asian woman
      after liver transplantation. The related problems are also discussed.

PMID- 9607268
TI  - Isolated fetal ascites: five cases report.
AB  - Isolated fetal ascites is a rare abnormality that can be detected prenatally by
      sonography. Fetuses with transient or isolated ascites were reported to have a
      good outcome if the specific etiology is confirmed and the appropriate treatment
      is given. In this report, we present 5 cases of nonimmune fetal ascites of
      different etiologies and obstetric managements. Fetuses that presented with
      generalized hydrops, chromosomal abnormalities and viral etiologies were
      excluded. Four of the fetuses survived without major neonatal complications,
      which included one chyloperitoneum, one meconium peritonitis and 2 idiopathic
      causes. Spontaneous resolution occurred in three cases. The one treated with
      prenatal paracentesis did not experience respiratory distress after birth but the
      other who did not undergo the procedure showed neonatal respiratory distress. The
      only neonatal mortality was a case involving intestinal obstruction who developed
      necrotizing enterocolitis four days after the surgery. Nonimmune fetal ascites
      can have a good outcome by using ultrasound in establishing the specific prenatal
      diagnosis and surveillance.

PMID- 9607269
TI  - Minimal access surgery in children: the use of laparoscopy for management of
      pediatric ovarian teratoma: a case report.
AB  - This article presents a case of left ovarian teratoma in a young child. Prompt
      diagnosis was made using real-time ultrasound, computed tomography (CT) and
      laparoscopy. The latter was used for performing tumor enucleation. We recommend
      that laparoscopy precede laparotomy and be done more routinely in the young
      patient.

PMID- 9607270
TI  - Partial trisomy 13 [46,XY,dup(13)(q14-31)]: a case report.
AB  - We report a fetus with partial trisomy 13 [46,XY,dup(13)(q14-31)] which was found
      during an amniocentesis performed due to the age of the mother. This duplication
      segment (13q 14-31) has not been reported in literature. The clinical features of
      our patient included cleft lip/palate, low set ears, depressed nasal bridge,
      hypertelorism, and epicanthal fold. After termination of the pregnancy, the fetus
      was sent for an autopsy. The autopsy report was compatible with the gross
      findings and no other abnormalities, including central nervous, cardiac, and
      renal system, were found. The level of maternal alpha-fetoprotein, 2.67 MoM, was
      opposite with the common phenomenon in complete trisomy 13.

PMID- 9607271
TI  - Primary left atrial malignant mesenchymoma: a case report.
AB  - Primary malignant mesenchymoma involving the heart is extremely rare. It usually
      has a poor prognosis. We report a case of malignant mesenchymoma originating in
      the left atrium with protrusion into the right pulmonary veins. Clinically, this
      patient presented with congestive heart failure, hemoptysis and systemic arterial
      embolization. Transthoracic and transesophageal echocardiography revealed a huge
      mass originating in the posterior wall of the left atrium with extension into
      both upper and lower right pulmonary veins. An elevated pulmonary arterial wedge
      pressure, moderate pulmonary hypertension and stenosis of the lower abdominal
      aorta were found during cardiac catheterization. Magnetic resonance imaging with
      angiography disclosed a tumor mass over the abdominal aorta above the bifurcation
      with protrusion into the right common iliac artery. This patient underwent
      surgical resection of the cardiac tumor and postoperative adjuvant chemotherapy.
      The pathological finding of a tumor containing several cellular types of sarcoma
      confirmed the diagnosis of malignant mesenchymoma.

PMID- 9607272
TI  - Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS): a case report.
AB  - Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is a rare
      congenital disorder characterized by a massively enlarged urinary bladder without
      mechanical outlet obstruction and microcolon, as well as a hypoperistaltic bowel
      with normal ganglion cell distribution. We report one such case to discuss the
      findings of antenatal ultrasound and the radiologic and pathologic features of
      this condition.

PMID- 9607273
TI  - Granulocytic sarcoma presenting as a giant breast tumor in a pregnant woman: a
      case report.
AB  - We report a case of granulocytic sarcoma (chloroma) presenting as a giant breast
      tumor in a pregnant woman with no history of leukemia. The case was initially
      diagnosed as medullary carcinoma on a biopsy specimen and a modified radical
      mastectomy was performed. The diagnosis of granulocytic sarcoma requires the
      pathologist's high index of suspicion. The presence of immature eosinophils was
      an important clue. Leder's chloroacetate esterase stain; immunostaining for
      myeloperoxidase, CD34, CD43, CD68, and lysozyme; and ultrastructural finding of
      cytoplasmic lysosomal granules and Auer bodies all aided in confirming the
      diagnosis. It is imperative to recognize granulocytic sarcoma to avoid
      unnecessary surgery. Granulocytic sarcoma should be included in the differential
      diagnosis of breast tumors, especially in tumors with diffuse proliferation of
      small tumor cells.

PMID- 9607274
TI  - Malakoplakia of the mesocolon with gastric serosa invasion: a case report and
      review of the literature.
AB  - Malakoplakia is a rare, granulomatous, inflammatory disease. The clinical
      presentation and radiological appearance of the malakoplakia mimics a malignant
      tumor. In this article we describe a case of the malakoplakia of the mesocolon
      with invasion into the serosa of the stomach. The frozen section report
      considered the lesion to be a malignancy. The definitive diagnosis depended on
      microscopic detection of Michaelis-Gutmann bodies by electronic microscope. We
      review the current literature about the malakoplakia of gastrointestinal tract,
      and focus on the pathogenesis, clinical manifestation, diagnosis and treatment.

PMID- 9607275
TI  - Total hip arthroplasty in Salmonella coxitis: four cases report.
AB  - Suppurative coxitis induced by salmonella is rarely reported in the literature.
      Furthermore, reconstruction with a total hip arthroplasty (THA) in such patients
      has never been reported. However, in this study, we present 4 cases; 2 normal
      male patients and 2 female patients with underlying systemic lupus erythematosus
      (SLE). The ages range from 26 to 61 years. All 4 cases revealed growth of group B
      salmonella from the cultures of synovial fluid. They all received THA after the
      infections were eradicated. The functional assessment of pain, range of motion,
      walking ability together with the radiographic assessment were used according to
      the new hip score system. After a minimum follow-up of 2 years, all of the
      reconstructed hips showed good to excellent results since no infections recurred
      during this period. Although the long-term results are uncertain, the short-term
      clinical advantage of THA in the treatment of quiescent salmonella coxitis is
      encouraging.

PMID- 9607276
TI  - Congenital renal arteriovenous malformations: two cases report.
AB  - Congenital arteriovenous malformation (AVM) of the kidney is a rare condition.
      Rupture of an AVM in the kidney may cause hematuria, flank pain, and urinary
      retention due to clots. We report 2 cases of congenital renal AVM. Both were
      treated with transcatheter renal arterial embolization. The signs and symptoms
      disappeared after embolization. On follow-up, renal function testing with a DMSA
      scan revealed only focal loss of renal cortical function. The clinical courses of
      2 cases are reported and the literature is reviewed.

PMID- 9607277
TI  - [Use of densitometry examinations for evaluation of proximal femur fracture risk
      in people over 50 years of age].
AB  - The paper presents the use of dual energy X-ray absorptiometry for selecting
      patients with high risk of proximal femur fracture. A group of 63 patients with
      fracture has been compared with a group of 306 patients who fell down but did not
      sustain a fracture, all individuals aged over 60. Most significant bone density
      decrease (p < 0.001) presented as Z indices related to young population was found
      in all three examined areas of the proximal femur. The difference between the
      groups ranged between 1.62 to 2.19 SD depending on the area and the sex.
      Threshold values for ZYA have been established. For the femoral neck it was -1.3
      SD, for Ward's triangle -1.5 SD and for trochanteric area -0.4 SD.

PMID- 9607278
TI  - [Surgical treatment of knee flexion contracture in children with flaccid limb
      paralysis using surgical procedures in soft tissues under the knee and serial
      casting].
AB  - Surgical technique and results of surgical correction for substantial flexion
      contracture of the knee in 15 children with spina bifida or other spinal
      conditions with lower extremities paresis is presented. Extensive posterior
      capsulotomy, occasionally supplemented with posterior cruciate sectioning is
      necessary to correct considerable flexion contracture of the knee. The technique
      is also effective in congenital flexion contracture with no articular surfaces
      deformity. Serial redressing and casting are imperative in postoperative
      management.

PMID- 9607279
TI  - [Evaluation of results after arthroscopic reconstruction of the anterior cruciate
      ligament with a free graft of the patellar ligament].
AB  - From among 312 patients treated with arthroscopic anterior cruciate ligament
      reconstruction (one-incision, transtibial with the use of ipsilateral bone
      patellar tendon-bone autograft) between 1992 and 1994 256 (82%) were reviewed
      with a mean follow-up of 26.4 months. An aggressive rehabilitative protocol
      advocated by Shelbourne has been employed. Stability of the knee has been
      assessed with KT-1000 arthrometer and IKDC and OAK forms served to evaluate the
      results. In 77% of the cases nearly normal function of the knee has been restored
      (87% excellent and good results in OAK form). Arthroscopic technique and
      aggressive rehabilitation decreased the number of patients with peripatellar pain
      and improved patient's acceptance of the management. Competitive athletes seem to
      achieve best end-results.

PMID- 9607280
TI  - [Osteosynthesis with elastic nailing for treatment of tibial fracture].
AB  - Results of treatment of 163 tibial fractures in 47 females and 116 males aged 15
      76 operated with closed elastic intramedullary osteosynthesis are presented. A
      bundle of universal intramedullary nails preshaped depending on fracture pattern
      served for osteosynthesis in 144 closed fractures, 18 open fractures of first
      degree and 1 second degree open fracture. In all cases but one fracture healed.
      Late results were assessed in 70 cases. There were 46 good results, 23 fair and 1
      poor result. Simple surgical technique, good stability, stimulating of bone
      healing by compression and minor risk of infection constitute advantages of this
      method.

PMID- 9607281
TI  - [Treatment for recurrent clubfoot with the Ilizarov technique].
AB  - Jlizarov technique was used to treat 34 recurrent clubfeet in 31 children between
      1993 and 1996. No additional surgery was done; various configurations of the
      distractor were employed. The age at the operation ranged from 2.5 to 14 years
      (mean 6.7) and mean follow-up was 22 months (range 9-31 months). Twenty-six
      results were rated good, 4 fair and 4 poor. The authors claim ilizarov method is
      contraindicated in cerebral palsy and meningomyelocele. The ideal arrangement of
      the distractor is hinge connection between all rings and semi-rings allowing for
      simultaneous correction of all components of the deformity.

PMID- 9607282
TI  - [Late results of the Harrington treatment method for posttraumatic injuries of
      the thoracic and lumbar spine].
AB  - At Stoleczne Centrum Rehabilitacji Harrington method along with Weiss spring
      alloplasty has been introduced for fractured spine stabilization in the early
      seventies. A modified Bacal-Wierusz (BW) distractor has been mainly used to
      stabilize the spine after trauma related fracture. The paper presents
      neurological and radiological results of Harrington method used within thoracic
      and lumbar spine in 86 patients between 1973 and 1993. There were 36 cases of
      plegia, 44 paretic patients and 6 cases with no neurological impairment. Thoraco
      lumbar spine has been involved in 66% and lumbar spine in 17%. Mean follow-up was
      6 years. Loss of the correction achieved at the surgery has been determined after
      analysis of the final radiographs. In radiological evaluation 66% results were
      rated good. Neurological improvement occurred in 37% and remarkable improvement
      in 16% of cases. The authors believe Harrington method does not provide good,
      triplanar stabilization for the spine.

PMID- 9607283
TI  - [Neurologic complications of lumbar osteochondrosis].
AB  - Four cases (2 females and 2 males aged 18-22) of lumbar spine osteochondrosis
      with massive defects within end-plates and vertebral bodies are presented. In 3
      cases bony overgrowth of posterior vertebral body wall with marginal spur
      occurred. Huge prolapse of annulus fibrosus occurred in one case. Neurological
      deficits appeared in all 4 cases. Bony overgrowth has been excised in 3 cases,
      nucleotomy accompanied one of them. The remaining patient required excision of
      the disc and segmental fusion. Good results were achieved in all above patients.
      The author recommends this treatment in similar cases.

PMID- 9607284
TI  - [The use of the ulnar artery in hand replantation].
AB  - A method for restoring arterial circulation at replantation of the metacarpus
      with reversed ulnar artery is presented. It was employed in 31 years old patient
      who underwent replantation of the metacarpus with index, middle and ring finger.
      The little one was abandoned due to the vast damage. Great defect made end-to-end
      anastomosis not feasible. Reversed ulnar artery bypass served to restore arterial
      circulation without need for shortening of the metacarpals. Numerous
      presentations stressing arterial bypass advantages provoked our attempt to use
      this method. After half a year good functional and cosmetic result has been
      achieved.

PMID- 9607285
TI  - [Socioeconomic sequelae to hand injuries].
AB  - Remote results of hand injuries in 78 patients (93% males, 7% females) aged 16-82
      (mean 39 years) were analyzed statistically and economically. Injuries sustained
      at work constituted 61%. All patients were operated on emergency basis, hospital
      stay ranged 1-93 days (mean 14 days). Further treatment on an outpatient basis
      lasted 4.5 months on an average. According to own 3-grade scale 24% results were
      rated good, 33%-fair and 43%-poor. Fifty-one per cent of patients resumed
      previous occupation, 17% found less demanding work and 15% were unable to work.
      Accident compensation fund was granted to 56% of patients. Great social cost of
      hand injuries is underlined in the paper.

PMID- 9607286
TI  - [Use of bone cements with added methotrexate for stabilization of pathologic
      fractures and filling of long bone defects in cases of neoplasm metastasis].
AB  - Preliminary results of surgical treatment in 24 patients with pathologic
      fractures or metastatic long bone defects impending fracture are presented.
      Fourteen females and 10 males aged 36-72 years with femoral (18 cases), tibial (4
      cases) or humeral (2 cases) involvement were followed-up for 6-48 months. In 12
      patients the pain ceased or decreased, 3 patients occasionally required non
      narcotic analgesics, in 9 cases the pain continued. All patients with lower
      extremity involvement were able to ambulate with an aid of walking sticks, 2
      patients with humeral fracture resumed activities of daily living. Nine patients
      with multiple metastases to the lungs and spine died on average 15 months after
      surgery. The longest survival rate was found in patients with kidney cancer-19
      months, ovary cancer-17 months and breast cancer 15 months. No postoperative
      complications were found. In 2 patients fracture fixation lost their stability
      after 8 and 10 weeks due to excessive weight bearing.

PMID- 9607287
TI  - [An unusual case of chondrosarcoma in a 5-year old boy].
AB  - A case of chondrosarcoma in 5 years old boy is presented. This type of neoplasm
      is extremely rare in this age group usually affecting patients in their forties
      and fifties. The tumor was located in the acetabular part of the ilium, ischial
      bone and the capsule what, again, is very rare, especially in children.
      Radiographs were atypical; there were no cloudy calcifications characteristic for
      malignant chondral tumors. The boy spent 2.5 years in several hospitals with
      various diagnoses being treated accordingly. The surgery performed was not
      radical: focal excision of the tumor was done and the capsule was entirely
      removed. No signs of avascular necrosis and no signs of neoplastic process
      recurrence were observed during 3 years follow-up.

PMID- 9607288
TI  - [Gigantic liposarcoma of the lower extremity--case report].
AB  - A case of gigantic liposarcoma of the lower extremity in 42 years old female is
      presented. The tumor grew extremely fast and reached gigantic size. Over one year
      follow-up did not reveal any local recurrence or metastases.

PMID- 9607289
TI  - [Malignancy of the scapular exostosis].
AB  - Secondary form of chondrosarcoma developed on the ground of scapular exostosis in
      27 years old male is presented. Two years after surgical excision no recurrence
      was found, both functional and cosmetic results were good.

PMID- 9607290
TI  - [Endoscopic ultrasonography in the staging of esophageal cancer. Therapeutic
      implications].
AB  - Endoscopic ultrasonography (EUS) provides accurate visualization of the different
      layers of the gastrointestinal wall and surrounding structures, allowing TN
      staging of tumors prior surgery. The aim of this study was to evaluate the
      sensitivity, specificity and accuracy of EUS in the staging of esophageal
      carcinoma as well as its applicability and usefulness in tumors with
      nontraversable stenoses. EUS was performed in 43 patients with esophageal
      carcinoma. The technique was carried out with a radial echoendoscope under
      sedation with i.v. midazolam. Both, the infiltration of the tumor through the
      layers of the esophageal wall (T staging) and the presence of lymph nodes in
      different areas (N and M staging) were determined. In cases with nontraversable
      stenoses, only the proximal tumor margin was assessed by means of EUS. EUS showed
      T1 stage in only one case and more advanced stages in the remaining patients: T2
      (n = 12), T3 (n = 22) and T4 (n = 4). We know the outcome of 28 patients, 14 of
      whom underwent surgery. In these patients, the sensitivity for T and N staging
      was 86% and 92% respectively, and the accuracy 86% in both. Both, T and N, were
      overstaged in one case (7%) and understaged in another (7%). The tumor caused
      nontraversable stenoses in 59% of patients (n = 26). In 4 patients the staging
      could not be assessed with sufficient reliability. In the subgroup of patients
      with nontraversable stenoses who underwent surgery, the accuracy of EUS when
      comparing with histopathology was 80%. Endoscopic ultrasonography has a high
      sensitivity and accuracy in the staging of esophageal tumors even in cases with
      nontraversable stenoses.

PMID- 9607291
TI  - [The value of endoscopic ultrasonography in the study of submucosal tumors of the
      digestive tract].
AB  - Twenty-one consecutive patients with 24 possible submucosal lesions of the
      digestive tract were studied. Endoscopic ultrasonography (EUS) differentiated
      between 17 true positive submucosal tumors and 3 true negative extrinsic
      compressions. False positives were interpreted in 3 cases and in one patient no
      lesion was echoendoscopically observed (false negative). The sensitivity was 94%,
      the specificity 50% and the positive and negative predictive values were 82% and
      75%, respectively. In conclusion, EUS may be the method of choice for the study
      of submucosal tumors since it allows visualization of the five layers of the wall
      of the digestive tract in which a tumor may originate, determination of its
      sonographic features, depth and exact size, in addition to the invasion of
      neighboring organs. Moreover, EUS may aid in collecting material for cytology and
      microscopy by fine needle aspiration puncture (FNAP) by EUS.

PMID- 9607292
TI  - [Celiac disease of the adult following orthotopic liver transplantation.
      Description of a case].
AB  - A case of celiac disease of the adult is herein described in a patient with a
      history of orthotopic liver transplantation because of cirrhosis due to hepatitis
      C virus. The patient presented with a decrease in the levels of cyclosporinemia,
      diarrhea and an increase in transaminases. This is an infrequent form of
      presentation leading to differential diagnosis with a complication related to the
      liver disease.

PMID- 9607293
TI  - [Hepatitis associated with treatment with lovastatin. Presentation of 2 cases].
AB  - Two women of 57 and 59 years of age, presented anicteric hepatitis at 9 months
      and 3 years, respectively, of the initiation of treatment with lovastatin (20
      mg/day) for hypercholesterolemia. In both cases other causes of liver damage were
      excluded and the analytical alterations normalized within a few weeks following
      discontinuation of the medication.

PMID- 9607294
TI  - [Free bowel perforation as the onset and as a complication in the evolution of
      crohn's disease].
AB  - Free bowel perforation is a relatively infrequent complication of Crohn's
      disease. It may present during the evolution of the disease or, occasionally, in
      the onset of the same and may involve the small intestine or colon. We herein
      present 4 cases, three of ileal localization and one of colonic localization. In
      one of the 3 former cases and the latter case perforation took place prior to
      diagnosis of the disease. Review of the literature was performed with respect to
      the frequency, pathogenesis and characteristics of this complication and the
      importance of determined diagnostic techniques such as echography and CAT in
      addition to the most adequate treatment are commented upon.

PMID- 9607295
TI  - [Volvulus of the gallbladder. Description of a case].
AB  - Volvulus of the gallbladder is infrequent and is predominantly observed in
      elderly women, being related to anatomical abnormalities of the gallbladder
      which, associated with other factors, favor twisting. This is commonly diagnosed
      as acute cholecystitis, causing severe, acute abdominal pain with a rapid
      evolution which may lead to the death of the patient if emergency surgery is not
      performed. A case of gallbladder volvulus diagnosed as acute appendicitis is
      presented as is a review of the literature.

PMID- 9607296
TI  - [Diagnosis of esophageal cancer].

PMID- 9607297
TI  - [Hepatorenal syndrome].

PMID- 9607298
TI  - [Notes on the history of hepatology].

PMID- 9607299
TI  - [Hepatitis from ecstasy].

PMID- 9607300
TI  - [Epidermoid carcinoma of the esophagus in caustic esophageal stenosis].

PMID- 9607301
TI  - [Acute hepatic failure by phenytoin].

PMID- 9607302
TI  - Amyloidogenic determinant as a substrate recognition motif of insulin-degrading
      enzyme.
AB  - Insulin-degrading enzyme (IDE) is an evolutionarily conserved neutral thiol
      metalloprotease expressed in all mammalian tissues whose biological role is not
      well established. IDE has highly selective substrate specificity. It degrades
      insulin, glucagon, atrial natriuretic peptide, transforming growth factor alpha
      but does not act on related hormones and growth factors. The structural
      properties determining whether a peptide is an IDE substrate are essentially
      unknown. The reported cleavage sites are not consistent with simple peptide-bond
      recognition and it was proposed that IDE recognizes in its substrates some
      elements of tertiary structure. We noticed that although IDE substrates are
      functionally unrelated, the majority of them share a specific property, an
      ability to form under certain conditions amyloid fibrils. Utilizing the residue
      pattern recognition procedure, this study reveals a common motif in the sequences
      of IDE substrates, HNHHHPSH, where H is wholly or partly hydrophobic character, N
      is small and neutral, P is polar, and S is polar and/or small amino acid residue.
      It is proposed that this sequence motif predetermines a structure recognized by
      IDE. The identified motif appears to be essentially the same as the proposed
      earlier consensus sequence for amyloid-forming peptides [Turnell and Finch, J.
      Mol. Biol. 227 (1992) 1205-1223]. The study suggests that IDE may play a role in
      elimination of potentially toxic amyloidogenic peptides.

PMID- 9607303
TI  - Diadenosine oligophosphates (Ap(n)A), a novel class of signalling molecules?
AB  - The diadenosine oligophosphates (Ap(n)A) were discovered in the mid-sixties in
      the course of studies on aminoacyl-tRNA synthetases (aaRS). Now, more than 30
      years later, about 300 papers have been published around these substances in
      attempt to decipher their role in cells. Recently, Ap(n)A have emerged as
      intracellular and extracellular signalling molecules implicated in the
      maintenance and regulation of vital cellular functions and become considered as
      second messengers. Great variety of physiological and pathological effects in
      mammalian cells was found to be associated with alterations of Ap(n)A levels (n
      from 2 to 6) and Ap3A/Ap4A ratio. Cell differentiation and apoptosis have
      substantial and opposite effects on Ap3A/Ap4A ratio in cultured cells. A human
      Ap3A hydrolase, Fhit, appeared to be involved in protection of cells against
      tumourigenesis. Ap3A is synthesised by mammalian u synthetase (TrpRS) which in
      contrast to most other aaRS is unable to synthesise Ap4A and is an interferon
      inducible protein. Moreover, Ap3A appeared to be a preferred substrate for 2-5A
      synthetase, also interferon-inducible, priming the synthesis of 2' adenylated
      derivatives of Ap3A, which in turn may serve as substrates of Fhit. Tumour
      suppressor activity of Fhit is assumed to be associated with involvement of the
      Fhit.Ap3A complex in cytokine signalling pathway(s) controlling cell
      proliferation. The Ap(n)A family is potentially a novel class of signal
      transducing molecules whose functions are yet to be determined.

PMID- 9607304
TI  - Identification of a cytoplasmic motif in the erythropoietin receptor required for
      receptor internalization.
AB  - Erythropoietin (EPO) promotes the viability, proliferation and differentiation of
      mammalian erythroid progenitor cells via its specific cell surface receptor. The
      EPO receptor (EPO-R) is a member of the cytokine receptor superfamily and is
      comprised of one identified subunit which homodimerizes upon ligand binding. To
      study the role of the intracellular domain of the EPO-R in the endocytosis of
      EPO, we compared the rate and extent of 125I-EPO endocytosis by wild type (wt)
      EPO-R and five cytoplasmically truncated EPO-Rs: 1-251 EPO-R, 1-257 EPO-R, 1-267
      EPO-R, 1-276 EPO-R and 1-306 EPO-R which contain 4, 10, 20, 29 or 59 amino acids
      of the cytoplasmic domain, respectively. We also studied an EPO-R mutant (PB)
      which lacks amino acid residues 281-300 of the cytoplasmic domain. The
      experiments were conducted in COS 7 cells transfected with the EPO-R cDNAs and in
      Ba/F3 cells stably expressing the wt EPO-R, 1-251 or 1-257 EPO-R. Cells
      expressing wt EPO-R, PB EPO-R (delta281-300), 1-276 EPO-R or 1-306 EPO-R
      internalized approximately 50% of 125I-EPO bound to the cell surface, while cells
      expressing 1-251, 1-257 or 1-267 EPO-R internalized only 25% of the bound 125I
      EPO. The steady-state expression levels of these latter receptors on the cell
      surface were typically 2-5-fold higher than wt EPO-R. Our data indicate that
      amino acid residues 267-276 (FEGLFTTHK) of the EPO-R cytoplasmic domain may have
      a role in receptor internalization. Metabolic labeling experiments suggest that
      in transiently transfected COS 7 cells most of the wt EPO-R and 1-257 EPO-Rs do
      not exit the ER and may be degraded there. The half-life of both receptors was
      essentially similar and was in the range of 1 h. In Ba/F3 cells the mature Golgi
      processed 1-257 EPO-R was more stable than the corresponding form of the wt EPO
      R, possibly contributing to its higher cell surface expression.

PMID- 9607305
TI  - Rapid and irreversible inhibition of creatine kinase by peroxynitrite.
AB  - We examined the ability of peroxynitrite and other .NO-derived oxidants to
      inhibit creatine kinase (CK). Peroxynitrite potently inhibited CK activity and
      depleted protein thiols. The rate constant for this reaction was 8.85x10(5) M(-1)
      s(-1). Glutathione did not reactivate CK activity nor did it regenerate protein
      thiol content. In contrast, glutathione reactivated CK, and regenerated protein
      thiols, after inhibition by either .NO or oxidized glutathione (GSSG).
      Peroxynitrite did not irreversibly inhibit CK after it had been treated with GSSG
      to block protein thiols. We conclude that thiol oxidation is a critical event
      leading to inactivation of CK by peroxynitrite.

PMID- 9607306
TI  - Stress-responsive expression of genes for two-component response regulator-like
      proteins in Arabidopsis thaliana.
AB  - Four cDNAs that encode two-component response regulator-like proteins were cloned
      from Arabidopsis thaliana. Putative proteins (ATRR1-4) contain a receiver domain
      with a conserved aspartate residue - a possible phosphorylation site - at the N
      terminal half. ATRR2 lacks the C-terminal half; the others contain a C-terminal
      domain abundant in acidic amino acids or proline residues. ATRR1 and ATRR2 are
      expressed more in roots than in other tissues and are induced by low temperature,
      dehydration and high salinity. Levels of ATRR3 and ATRR4 were not affected by
      stress treatments. These results suggest that ATRRs play distinct physiological
      roles in Arabidopsis, and that some are involved in stress responses.

PMID- 9607307
TI  - Release of matrix proteins from mitochondria to cytosol during the prereplicative
      phase of liver regeneration.
AB  - 70% partial hepatectomy (PH) in the rat causes a release, into the cytosolic
      fraction, of mitochondrial matrix proteins, namely the mitochondrial isoform of
      aspartate aminotransferase (mAAT) and malate dehydrogenase (MDH), during the
      first 24 h after PH, when no growth of the residual liver is observed. After this
      time interval, the weight of the liver starts to increase and the normal weight
      is reached at 96 h after PH. This proliferative phase is characterized by a
      progressive recovery of the normal levels of intramitochondrial activities of
      mAAT and MDH. Mitochondria isolated at 24 h after PH show a membrane
      permeabilization to sucrose accompanied by a release of matrix enzymes; both are
      blocked by cyclosporin A. These results suggest an alteration of mitochondrial
      membrane integrity, during the prereplicative phase of liver regeneration, with
      the occurrence of an increased permeability that allows the passage into the
      cytosol of matrix enzymes.

PMID- 9607308
TI  - Intragenic recombinations in rotaviruses.
AB  - In this paper, evidence for intragenic recombination in the VP7 gene between
      rotavirus strains bearing different serotypes is demonstrated for the first time.
      Intragenic recombination may be one of the escaping mechanisms from the host
      immune system for rotavirus. This process involves exchanging antigenic regions,
      thus questioning the use of multivalent vaccines for the prevention of rotavirus
      infection.

PMID- 9607309
TI  - Identification of a novel human phosphatidic acid phosphatase type 2 isoform.
AB  - Two human isoforms of membrane associated phosphatidic acid phosphatase have been
      described (PAP-2a and -2b), and both enzymes have been shown to have broad
      substrate specificity and wide tissue distribution [Kai et al., J. Biol. Chem.
      272 (1997) 24572-24578]. With this report we describe a third isoform, PAP-2c,
      that we found by searching the database of expressed sequence tags (dbEST) with
      PAP-2a and PAP-2b sequences. Key structural features described previously in PAP
      2a and -2b, including the glycosylation site, putative transmembrane domains, and
      the proposed catalytic site, are conserved in the novel phosphatase. The kinetics
      of the three enzymes were compared using as substrates phosphatidic acid,
      lysophosphatidic acid, and N-oleoyl ethanolamine phosphatidic acid. Km values for
      each of the substrates, respectively, were (in microM) PAP-2a: 98, 170, 116; PAP
      2b: 100, 110, 56; and PAP-2c: 150, 340, 138. Expression of PAP-2c mRNA is more
      restricted than the two previously described isoforms.

PMID- 9607310
TI  - GLUT4 translocation by insulin in intact muscle cells: detection by a fast and
      quantitative assay.
AB  - We report a rapid and sensitive colorimetric approach to quantitate the amount of
      glucose transporters exposed at the surface of intact cells, using L6 muscle
      cells expressing GLUT4 containing an exofacial myc epitope. Unstimulated cells
      exposed to the surface 5 fmol GLUT4myc per mg protein. This value increased to 10
      fmol/mg protein in response to insulin as 2-deoxyglucose (10 microM) uptake
      doubled. The results are substantiated by immunofluorescent detection of GLUT4myc
      in unpermeabilized cells and by subcellular fractionation. We further show that
      wortmannin and the cytoskeleton disruptors cytochalasin D and latrunculin B
      completely blocked these insulin effects. The rapid quantitative assay described
      here could be of high value to study insulin signals and to screen for potential
      anti-diabetic drugs.

PMID- 9607311
TI  - Caspases disrupt mitochondrial membrane barrier function.
AB  - Mitochondrial intermembrane proteins including cytochrome c are known to activate
      caspases. Accordingly, a disruption of the mitochondrial membrane barrier
      function with release of cytochrome into the cytosol has been shown to precede
      caspase activation in a number of different models of apoptosis. Here, we
      addressed the question of whether caspases themselves can affect mitochondrial
      membrane function. Recombinant caspases were added to purified mitochondria and
      were found to affect the permeability of both mitochondrial membranes. Thus,
      caspases cause a dissipation of the mitochondrial inner transmembrane potential.
      In addition, caspases cause intermembrane proteins including cytochrome c and AIF
      (apoptosis-inducing factor) to be released through the outer mitochondrial
      membrane. These observations suggest that caspases and mitochondria can engage in
      a circular self-amplification loop. An increase in mitochondrial membrane
      permeability would cause the release of caspase activators, and caspases, once
      activated, would in turn increase the mitochondrial membrane permeability. Such a
      self-amplifying system could accelerate the apoptotic process and/or coordinate
      the apoptotic response between different mitochondria within the same cell.

PMID- 9607312
TI  - Features of replicative senescence induced by direct addition of antennapedia
      p16INK4A fusion protein to human diploid fibroblasts.
AB  - The p16INK4A cyclin-dependent kinase (Cdk) inhibitor is now recognized as a major
      tumor suppressor that is inactivated by a variety of mechanisms in a wide range
      of human cancers. It is also implicated in the mechanisms underlying replicative
      senescence since p16INK4A RNA and protein accumulate as cells approach their
      proscribed limit of population doublings in tissue culture. To obtain further
      evidence of its role in senescence, we have sought ways of overexpressing
      p16INK4A in primary human diploid fibroblasts (HDF). To circumvent the low
      transfection efficiency of primary cells we have exploited a recombinant form of
      the full-length p16INK4A protein fused to a 16 amino acid peptide from the
      Drosophila antennapedia protein. This peptide has the capacity to cross both
      cytoplasmic and nuclear membranes allowing the direct introduction of the active
      protein to primary cells. Here, we show that antennapedia-tagged wild-type
      p16INK4A protein, but not a functionally compromised tumor-specific variant,
      causes G1 arrest in early passage HDFs by inhibiting the phosphorylation of the
      retinoblastoma protein. Significantly, the arrested cells display several
      phenotypic features that are considered characteristic of senescent cells. These
      data support a role for p16INK4A in replicative senescence and raise the
      possibility of using the antennapedia-tagged protein therapeutically.

PMID- 9607313
TI  - Rapid activation of the novel serine/threonine protein kinase, protein kinase D
      by phorbol esters, angiotensin II and PDGF-BB in vascular smooth muscle cells.
AB  - Protein kinase D (PKD) is a novel serine/threonine kinase structurally distinct
      from all protein kinase C (PKC) isoforms but which like classic and novel PKCs is
      activated by phorbol esters and diacylglycerol. This study investigated the
      regulation of PKD in vascular smooth muscle cells (VSMC) by physiological
      regulators of VSMC function and growth factors. Treatment of rabbit aortic VSMC
      with phorbol ester, angiotensin II and PDGF-BB all stimulated PKD activity in a
      time- and concentration-dependent manner in VSMC. The effect of angiotensin II
      was particularly rapid and potent (maximum stimulation within 1 min and at 0.5
      nM). In contrast, the maximum effect of PDGF-BB was obtained after 5 min. Other
      factors, including basic FGF, IGF-I, IGF-II, endothelin-1 and endothelin-2, had
      no effect on PKD activity in VSMC. These results show for the first time that PKD
      activity is regulated in VSMC, and is activated by the vasoconstrictor
      angiotensin II. PKD may be an important mediator for the biological function(s)
      of one or more PKC isoforms in VSMC and/or may represent a component of a novel
      PKC-independent signalling pathway in VSMC.

PMID- 9607314
TI  - Retinol-induced secretion of human retinol-binding protein in yeast.
AB  - Retinol-binding protein (RBP) functions as a transporter for retinol (vitamin A)
      in plasma in higher eukaryotes. We have successfully expressed human RBP in
      Saccharomyces cerevisiae, and its secretion was found to be induced by retinol
      also in this lower eukaryote. Reduced induction of secretion by retinol in a
      temperature-sensitive sec18-1 mutant that is blocked in secretion at the
      restricted temperature suggests that as in mammalian cells, RBP can be released
      from the endoplasmic reticulum upon addition of retinol. Thus, the molecular
      mechanism involved in retinol-dependent secretion of RBP appears to be conserved
      in yeast, and this points to yeast as a putative model system for studying
      retinol-regulated secretion of RBP. RBP purified from yeast was found to be
      indistinguishable from RBP purified from human plasma in several functional
      assays.

PMID- 9607315
TI  - Ca2+ channel sensitivity towards the blocker isradipine is affected by
      alternative splicing of the human alpha1C subunit gene.
AB  - L-type Ca2+ channels are important targets for drugs, such as dihydropyridines
      (DHPs), in the treatment of cardiovascular diseases. Channel expression is
      regulated by alternative splicing. It has been suggested that in the
      cardiovascular system tissue-specific expression of different L-type Ca2+ channel
      splice variants may underlie the observed differences in sensitivities to channel
      block by DHPs. We investigated the sensitivity of Ca2+ channel splice variants
      derived from the human alpha1C gene to the DHP isradipine. Among seven alpha1C
      channels we observed up to 10-fold differences in IC50 values for isradipine, as
      well as changes in the voltage dependence of DHP action.

PMID- 9607316
TI  - Xanthine oxidoreductase catalyses the reduction of nitrates and nitrite to nitric
      oxide under hypoxic conditions.
AB  - Xanthine oxidoreductase (XOR) catalyses the reduction of the therapeutic organic
      nitrate, nitroglycerin (glyceryl trinitrate, GTN), as well as inorganic nitrate
      and nitrite, to nitric oxide (NO) under hypoxic conditions in the presence of
      NADH. Generation of nitric oxide is not detectable under normoxic conditions and
      is inhibited by the molybdenum site-specific inhibitors, oxypurinol and (-)BOF
      4272. These enzymic reactions provide a mechanism for generation of NO under
      hypoxic conditions where nitric oxide synthase does not function, suggesting a
      vasodilatory role in ischaemia.

PMID- 9607317
TI  - Development of an antigen presentation system based on plum pox potyvirus.
AB  - The development of an antigen presentation system based on the plum pox potyvirus
      (PPV) is here described. The amino-terminal part of PPV capsid protein was chosen
      as the site for expression of foreign antigenic peptides. Modifications in this
      site were engineered to avoid the capability of natural transmission by aphids of
      this PPV vector. As a first practical attempt, different forms of an antigenic
      peptide (single and tandem repetition) from the VP2 capsid protein of canine
      parvovirus (CPV) were expressed. Both chimeras are able to infect Nicotiana
      clevelandii plants with similar characteristics to wild-type virus and remain
      genetically stable after several plant passages. The antigenicity of purified
      chimeric virions was demonstrated, proving the suitability of this system for
      diagnostic purposes. Moreover, mice and rabbits immunized with chimeric virions
      developed CPV-specific antibodies, which showed neutralizing activity.

PMID- 9607318
TI  - The interacting RNA polymerase II subunits, hRPB11 and hRPB3, are coordinately
      expressed in adult human tissues and down-regulated by doxorubicin.
AB  - We previously isolated the human RPB11 cDNA, encoding the 13.3 kDa subunit of RNA
      polymerase II, and demonstrated that expression of this subunit is modulated by
      doxorubicin. Using hRPB11 as bait in a yeast two-hybrid system, two cDNA variants
      encoding a second RNA polymerase II subunit, hRPB3, have now been isolated and
      characterized. These two hRPB3 mRNA species differed in 3' UTR region length, the
      longer transcript containing the AU-rich sequence motif that mediates mRNA
      degradation. Both hRPB11 and hRPB3 transcripts share a similar pattern of
      distribution in human adult tissues, with particularly high levels in both heart
      and skeletal muscle, and the expression of both is down-regulated by doxorubicin
      as found previously for the hRPB11 subunit. Taken together, these findings
      suggest that the interaction between hRPB3 and hRPB11 is fundamental for their
      function and that this heterodimer is involved in doxorubicin toxicity.

PMID- 9607319
TI  - Levels of expression of hRPB11, a core subassembly subunit of human RNA
      polymerase II, affect doxorubicin sensitivity and cellular differentiation.
AB  - We have previously shown that the human RNA polymerase II subunit 11 (hRPB11) is
      among the proteins specifically downregulated upon Doxorubicin (Dox) treatment of
      human cancer cell lines, and that Dox resistant clones derived upon drug
      selection express about 20% of the protein present in the original parental cell
      line. Given the prominent role that this subunit appears to have in eukaryotic
      cells, and the fact that its deletion causes lethality in yeast, we wanted to
      test the effect of the reintroduction of parental cell line levels of this
      subunit in Dox resistant colon cancer cells (LoVoDX). Stable transfectants of
      LoVoDX expressing parental (LoVoH) levels of hRPB11 showed a reduced sensitivity
      to the drug without changing the response of these cells to other
      chemotherapeutic agents, confirming a specific inverse correlation between
      cellular Dox sensitivity anti-hRPB11 levels of expression. In addition we show
      here that the levels of expression of this same RNA polymerase II subunit
      directly affect cellular differentiation, reducing the rate of cell
      proliferation, clonogenicity and increasing the expression of E-cadherin, a
      marker of epithelial cell differentiation. As expected from cells with these
      characteristics, upon in vivo administration of these clones in nude mice, we
      detected a significant reduction in the size and time of appearance of the
      primary tumors and overall metastatic capability. Finally, the role played by
      hRPB11 in regulating the transcription of specific genes is underlined by
      transient transfection experiments that show transactivation of the E-cadherin
      promoter by this protein.

PMID- 9607320
TI  - Proteolytic cleavage of HsRad51 during apoptosis.
AB  - The Rad51 gene of Saccharomyces cerevisiae is required for genetic recombination
      and recombinational repair of DNA strand breaks. In higher eukaryotes Rad51 is
      essential for embryonic development, and is involved in cell proliferation and
      DNA repair. Here we show that human Rad51 (HsRad51) is proteolytically cleaved
      during apoptosis in two T-lymphocyte cell lines, Jurkat and PFI-285. Apoptosis
      was induced by camptothecin or anti-Fas monoclonal antibody (anti-Fas mAb).
      HsRad51 was cleaved with similar kinetics as human poly(ADP-ribose) polymerase
      (HsPARP) after treatment with either agent. The time course of cleavage coincided
      with internucleosomal DNA fragmentation. The HsRad51 fragments observed in
      apoptotic cells were identical to those generated from in vitro translated (IVT)
      HsRad51 exposed to activated Jurkat S-100 extract in a cell-free system. In each
      case, cleavage of HsRad51 was abolished by acetyl-Asp-Glu-Val-Asp-aldehyde (Ac
      DEVD-CHO). However, cleavage of IVT HsRad51 could not be demonstrated using
      purified caspase-2, -3 or -6 to -10, and the identity of the responsible protease
      thus remains to be determined. In summary, we have shown that HsRad51 belongs to
      a group of repair proteins, including PARP and DNA-dependent protein kinase,
      which are specifically cleaved during the execution phase of apoptosis.

PMID- 9607321
TI  - Application of polymannosylated cystatin to surimi from roe-herring to prevent
      gel weakening.
AB  - A recombinant glycosylated cystatin with a polymannosyl chain was added to roe
      herring surimi for preventing gel weakening due to autolysis during cooking.
      Proteolysis of myosin heavy chain in the surimi was effectively suppressed while
      cooking at 90 degrees C for 20 min after preincubation at 40 degrees C for 30
      min. The glycosylation of cystatin improved the stability against heating as well
      as proteolysis by cathepsin D. This process markedly improved the texture of the
      cooked surimi gel with gel strength 2.5 times that of unglycosylated control
      cystatin.

PMID- 9607322
TI  - The CRH-ACTH-biogenic amine axis in invertebrate immunocytes activated by PDGF
      and TGF-beta.
AB  - In immunocytes from the mollusc Mytilus galloprovincialis, the major pathway
      followed by platelet-derived growth factor (PDGF)-AB and transforming growth
      factor (TGF)-beta1 in provoking the release of norepinephrine, epinephrine and
      dopamine into cell-free hemolymph (serum) is mediated by a corticotropin
      releasing hormone-adrenocorticotropin hormone (CRH-ACTH) biogenic amine axis.
      This axis not only annulled the inhibiting properties of PDGF-AB, it even
      reversed the latter's effect, while the inducing effect of TGF-beta1 was
      amplified. These findings show that non-classical immune-neuroendocrine
      molecules, such as PDGF-AB and TGF-beta1, are involved in building stress
      response, using the same conserved mechanisms present from invertebrates to
      vertebrates.

PMID- 9607323
TI  - Biochemical and phylogenetic analyses of methionyl-tRNA synthetase isolated from
      a pathogenic microorganism, Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis methionyl-tRNA synthetase (MetRS) has been cloned and
      characterized. The protein contains class I signature sequences but lacks the
      Zn2+ binding motif and the C-terminal dimerization appendix that are found in
      MetRSs from several organisms including E. coli MetRS. Consistent with these
      features, the enzyme behaved as a monomer in a gel filtration chromatography and
      did not contain the bound Zn2+. Nonetheless, it was active to the tRNAMet of E.
      coli as determined by in vivo genetic complementation and in vitro reaction.
      Phylogenetic analysis separated the M. tuberculosis and E. coli MetRSs into
      prokaryote and eukaryote-archaea group, respectively. This result is consistent
      with the taxonomic locations of the organism but is an interesting contrast to
      the case of its paralogous protein, isoleucyl-tRNA synthetase, and suggests that
      the two enzymes evolved in separate idiosyncratic pathways.

PMID- 9607324
TI  - Direct evidence of nitric oxide production from bovine aortic endothelial cells
      using new fluorescence indicators: diaminofluoresceins.
AB  - The measurement of nitric oxide (NO) is important for direct examination of the
      regulatory roles of NO in various biological systems. Diaminofluoresceins (DAFs),
      new fluorescence indicators for NO, were applied to detect the release of NO from
      bovine aortic endothelial cells (ECs). DAFs react with NO to yield the
      corresponding green-fluorescent triazolofluoresceins, which provide the
      advantages of specificity, sensitivity and a simple protocol for the direct
      detection of NO. Using these DAFs, we could detect the generation of NO not only
      from inducible NO synthase expressed in macrophages, but also from constitutive
      NO synthase expressed in ECs.

PMID- 9607325
TI  - Molecular dynamics study of the LS3 voltage-gated ion channel.
AB  - Molecular dynamics calculations have been carried out on a model of the LS3
      synthetic ion channel in a membrane mimetic environment. In the absence of an
      external electrostatic field, the LS3 channel, which consists of a bundle of six
      alpha-helices with sequence Ac-(LSSLLSL)3-CONH2, exhibits large structural
      fluctuations. However, in the presence of the field, the bundle adopts a well
      defined coiled-coil structure with an inner pore of water. The observed
      structural changes induced by the applied field are consistent with the proposed
      gating mechanism of the ion channel.

PMID- 9607326
TI  - Pervanadate inhibits mitogen-activated protein kinase kinase-1 in a p38MAPK
      dependent manner.
AB  - In baboon smooth muscle cells (SMCs), pervanadate has a biphasic dose-dependent
      effect on MEK-1 activity. After a 30 min incubation period, low concentrations (1
      10 microM) activate, while higher doses (30-100 microM) fail to stimulate MEK-1.
      One possibility is that higher doses of pervanadate induce an additional
      signaling pathway that inhibits MEK-1. Three lines of investigations provide
      support for the conclusion that this inhibitory effect is mediated by p38MAPK.
      First, pervanadate induces p38MAPK activity at concentrations that fail to
      activate MEK-1. Second, pervanadate-stimulated p38MAPK activity is maximal after
      a 10 min incubation, at a time, when MEK-1 activity disappears. Third, addition
      of the specific p38MAPK inhibitor SB203580 preserves MEK-1 activation by 100
      microM pervanadate. The inhibitory effect of p38MAPK is probably not due to a
      phosphorylation of MEK-1 although we can not rule out that other p38MAPK isoforms
      such as SAPK3 and SAPK4 may be involved, and may directly phosphorylate and
      inhibit MEK-1.

PMID- 9607327
TI  - Regulation of gelatinase B (MMP-9) in leukocytes by plant lectins.
AB  - The stimulatory or inhibitory effects of plant lectins on the production of
      gelatinase A (MMP-2) and gelatinase B (MMP-9) by mononuclear white blood cells
      was investigated by substrate zymography. Leukocyte cultures from 24-h old buffy
      coats were spontaneously activated and produced high levels of gelatinase B.
      Using such cultures the suppressing activity of the Datura stramonium, Viscum
      album, Bauhinia purpurea, Triticum aestivum and Maackia amurensis lectins on
      gelatinase B induction were demonstrated. When fresh leukocyte preparations from
      single blood donors were used, low levels of gelatinase B were produced. The
      induction of gelatinase B was confirmed for concanavalin A and
      phytohaemagglutinin (PHA-L4). In addition, the Urtica dioica, Calystegia sepium,
      Convolvulus arvensis and Colchicum autumnale lectins were documented as novel and
      potent inducers of gelatinase B. Since high circulating gelatinase B levels are
      associated with specific pathologies, including shock syndromes, the acute
      toxicity of many lectins might be partially mediated or influenced by gelatinase
      induction.

PMID- 9607328
TI  - Caveolin-3 is not an integral component of the dystrophin glycoprotein complex.
AB  - The dystrophin-glycoprotein complex is a multi-subunit protein complex that spans
      the muscle plasma membrane (sarcolemma) and forms a link between the
      intracellular cytoskeleton and the extracellular matrix. Caveolin-3, the muscle
      specific form of caveolin, is also a major structural and regulatory integral
      membrane protein found at the sarcolemma. Oligomers of caveolin-3 form the
      structural framework for small membrane pockets known as caveolae. We directly
      examined whether caveolin-3 is an integral component of the dystrophin
      glycoprotein complex by examining four common biochemical and cellular properties
      of proteins integrally bound to the dystrophin-glycoprotein complex. We found
      that caveolin-3 de-enriches with partial purification of the dystrophin
      glycoprotein complex although a small amount of caveolin-3 is present. Sucrose
      gradient fractionation and laminin affinity chromatography completely separate
      this residual caveolin-3 from the core components of the dystrophin-glycoprotein
      complex. We also show that caveolin-3 expression at the sarcolemma is not reduced
      in patients with primary mutations in either dystrophin or the sarcoglycans. This
      data demonstrates that localization of caveolin-3 to the sarcolemma occurs
      independently of the dystrophin-glycoprotein complex and that caveolin-3 is not
      an integral component of the dystrophin-glycoprotein complex.

PMID- 9607329
TI  - Prenylation of olivetolate by a hemp transferase yields cannabigerolic acid, the
      precursor of tetrahydrocannabinol.
AB  - A new enzyme, geranylpyrophosphate:olivetolate geranyltransferase (GOT), the
      first enzyme in the biosynthesis of cannabinoids could be detected in extracts of
      young leaves of Cannabis sativa. The enzyme accepts geranylpyrophosphate (GPP)
      and to a lesser degree also nerylpyrophosphate (NPP) as a cosubstrate. It is,
      however, specific for olivetolic acid; its decarboxylation product olivetol is
      inactive as a prenyl acceptor.

PMID- 9607330
TI  - How platelet aggregation affects B16BL6 melanoma cell trafficking.
AB  - In blood-borne metastasis, intravasated metastatic tumor cells are thought to
      localize at the target site via a series of processes involving platelet
      aggregation, adhesion to endothelium, and invasion through the basal membrane. In
      the present study, we examined how platelet aggregation contributes to the
      trafficking of metastatic tumor cells in vivo by use of an inhibitor of platelet
      aggregation. Highly invasive B16BL6 melanoma cells were labeled with [2-18F]2
      fluoro-2-deoxy-D-glucose and injected into mice to determine cell trafficking non
      invasively by positron emission tomography. Both platelet aggregation inhibitor
      cyclo(RSarDPhg), which could not inhibit metastasis, and metastatic inhibitor
      cyclo(GRGDSPA) suppressed the accumulation of B16BL6 cells in the lung by about
      12%, suggesting that platelet aggregation partly affects cell trafficking but not
      to a great extent, and that platelet aggregation is not the essential step for
      B16BL6 cell arrest in targets.

PMID- 9607331
TI  - A role for the signal transduction protein PII in the control of nitrate/nitrite
      uptake in a cyanobacterium.
AB  - In the cyanobacterium Synechococcus sp. strain PCC 7942, ammonium exerts a rapid
      and reversible inhibition of the nitrate and nitrite uptake, and the PII protein
      (GlnB) is differentially phosphorylated depending on the intracellular N/C
      balance. RNA/DNA hybridizations, as well as nitrate and nitrite uptake
      experiments, were carried out with the wild-type strain and a PII-null mutant.
      The transcriptional control by ammonium of the expression of the nir-nrt ABCD
      narB operon remained operative in the mutant but, in contrast to the wild-type
      strain, the mutant took up nitrate and nitrite even in the presence of ammonium.
      Moreover, the wild-type phenotype was restored by insertion of a copy of the wild
      type glnB gene in the genome of the PII-null mutant. These results indicate that
      the unphosphorylated form of PII is involved in the short-term inhibition by
      ammonium of the nitrate and nitrite uptake in Synechococcus sp. strain PCC 7942.

PMID- 9607332
TI  - Different domains of the ORL1 and kappa-opioid receptors are involved in
      recognition of nociceptin and dynorphin A.
AB  - In order to gain further insight into the functional architecture of structurally
      related G protein-coupled receptors, the ORL1 (nociceptin) and opioid receptors,
      we have constructed chimeras of ORL1 and mu-, delta- and kappa-opioid receptors,
      and compared their binding and functional properties with those of the parent
      receptors. We find in particular that a ORL1-kappa-opioid (O-K) hybrid construct
      has retained high affinity for non-type-selective opiate ligands, and has
      acquired the ability to bind and respond to enkephalins and mu- and/or delta
      opioid receptor-selective enkephalins analogs, thus behaving like a 'universal'
      opioid receptor. Most significantly however, whilst the ORL1 and kappa-opioid
      receptors display high binding preference (KD 0.1 vs. 100 nM) for their
      respective endogenous ligands, nociceptin and dynorphin A, the O-K chimeric
      receptor binds both nociceptin and dynorphin A, with high affinity (KD < 1 nM).
      Together, these data (i) add weight to the hypothesis that the extracellular
      loops of opioid receptors act as a filter for ligand selection, and (ii)
      demonstrate that different domains of the ORL1 and kappa-opioid receptors are
      involved in recognition of their endogenous peptide ligands.

PMID- 9607333
TI  - Antiparallel DNA duplex formation between alternating alpha d(GA)n and beta
      d(GA)n sequences.
AB  - Alternating polypurine d(GA)n, sequences exhibit a considerable polymorphism.
      Here we report that alpha d(GA) x d(GA) sequences form an antiparallel stranded
      duplex DNA at neutral pH. The spectroscopic, electrophoretic and thermodynamic
      properties of the alpha/beta chimeric oligodeoxynucleotide, 5'-d(GA)4(T)4 alpha
      d(AG)4T-3', support the formation of a hairpin structure with antiparallel
      strands in the stem. The optical properties of this novel antiparallel structure
      are different from the parallel stranded homoduplex formed by d(GA)G7. This
      alpha/beta hairpin has a remarkably high Tm of 44.5 degrees C in 0.4 M NaCl with
      a van't Hoff enthalpy comparable to that of a parallel d(GA)n duplex. Base
      pairing was confirmed by T4 polynucleotide ligase catalyzed joining of the
      alpha/beta hairpin to an antiparallel bimolecular duplex and by non-denaturing
      gel electrophoresis using duplexes containing sequence constraints. Both support
      the presence of alphaG-G and alphaA-A base pairing in the antiparallel 5'
      d(GA)4(T)4 alpha d(AG)4T-3' intramolecular duplex. This study adds to the
      polymorphic nature of alternating d(GA)n sequences as well as providing novel
      homopurine base pairing approaches for probing polypurine polypyrimidine
      sequences.

PMID- 9607334
TI  - Carotenoid mixtures protect multilamellar liposomes against oxidative damage:
      synergistic effects of lycopene and lutein.
AB  - Antioxidant activity of carotenoids in multilamellar liposomes assayed by
      inhibition of formation of thiobarbituric acid-reactive substances was in the
      ranking: lycopene> alpha-tocopherol > alpha-carotene > beta-cryptoxanthin >
      zeaxanthin = beta-carotene > lutein. Mixtures of carotenoids were more effective
      than the single compounds. This synergistic effect was most pronounced when
      lycopene or lutein was present. The superior protection of mixtures may be
      related to specific positioning of different carotenoids in membranes.

PMID- 9607335
TI  - Sperm capacitation is, after all, a prerequisite for both partial and complete
      acrosome reaction.
AB  - The acrosome reaction (AR) - an essential step in mammalian fertilization - can
      occur, according to the consensus, only in capacitated spermatozoa. In apparent
      contrast, recent reports have demonstrated that human spermatozoa incubated in
      vitro in an albumin-free medium and therefore believed to be non-capacitated, do
      undergo the AR. With the aim of determining unequivocally whether or not
      capacitation is required for the AR and whether albumin is essential for
      capacitation, we compared the potential to undergo partial and complete AR
      (induced by phorbol myristate ester or by the Ca2+ ionophore A23187) between
      human spermatozoa incubated in a capacitating medium, albumin-free medium, and
      non-capacitating medium. The results clearly demonstrate that capacitation is,
      after all, a prerequisite for both partial and complete AR. Albumin, on the other
      hand, is essential only for acquiring the capacity to undergo complete, not
      partial AR.

PMID- 9607336
TI  - The employment experience of 1995's graduates.

PMID- 9607337
TI  - Is there an increased risk of second primaries following prostate irradiation?
AB  - PURPOSE: To assess the risk of developing a second primary cancer following
      prostate irradiation compared to the underlying risk in patients with prostate
      cancer. METHODS AND MATERIALS: The baseline rate of secondary cancers following
      prostate cancer was obtained from a study of 18,135 patients from the Connecticut
      Tumor Registry, of whom only 12.5% received radiotherapy. These patients, with a
      mean age of 72 and a mean follow-up of 3.9 years, were compared to a cohort of
      543 patients (median age 70) with similar follow-up (median 3.9 years), all of
      whom were treated with definitive radiotherapy at Fox Chase Cancer Center. The
      possible association between various covariates (age, dose, palpation stage,
      field size, Gleason score, pretreatment PSA) and the development of a secondary
      cancer was assessed. RESULTS: 1,053 of 18,135 patients (5.8%) in the Connecticut
      Tumor Registry developed a second primary cancer compared with 31 of 543 (5.7%)
      patients treated with prostate radiation (p = 0.99). Although this risk increases
      gradually over time, it is not significantly different, at any time period,
      between the two groups of patients. Of the 31 secondary primaries in the
      irradiated group, 82% had a history of tobacco and/or alcohol use. Only melanomas
      were significantly increased compared to the expected rate in an age-matched
      population (p < 0.001). Five of the 31 secondary cancers occurred within the
      radiation field (four bladder, one colon), four within 3 years and only one
      occurred 9 years after radiotherapy. No association was found between age (<70
      vs. > or =70 and as a continuous variable), dose (<74 vs. > or =74 Gy), palpation
      stage (<T2C vs. > or =T2C), field size (prostate vs. pelvic), radiation technique
      (conventional vs. conformal), Gleason score (2-6 vs. 7-10), or pretreatment PSA
      (<15 vs. > or =15 and as a continuous variable) and the risk of developing a
      second primary. Although a lower radiation dose (as a continuous variable)
      correlated with an increased risk of developing a secondary cancer (p = 0.04),
      this phenomenon is likely due to differences in follow-up time. CONCLUSION: Up to
      at least 10 years, there is no increased risk of developing a second primary
      cancer following prostate irradiation compared to the baseline rate from prostate
      cancer itself. This risk is not higher in younger patients with localized disease
      (<T2C), who often must choose between surgery and radiation. The vast majority of
      secondary cancers occurred outside of the radiation field (84%) and/or within 3
      years of radiotherapy (97%), suggesting they were not caused by radiation. Most
      of these patients had lifestyles with predisposing risk factors. Patients with
      prostate cancer manifested a significantly increased risk of developing
      melanomas, suggesting that they may benefit from patient education and skin
      screening examinations.

PMID- 9607338
TI  - Radiation-associated morbidity in patients undergoing small-field external beam
      irradiation for prostate cancer.
AB  - PURPOSE: To quantify complication rates after small-field external beam
      irradiation for adenocarcinoma of the prostate in a uniformly treated patient
      population with long follow-up using a simple tool designed to identify subtle
      treatment-related side effects; and to identify clinical and technical variables
      associated with increased morbidity after irradiation. METHODS AND MATERIALS: A
      total of 441 patients with nonmetastatic adenocarcinoma of the prostate treated
      at the Joint Center for Radiation Therapy between 1985 and 1989 were eligible for
      analysis. Gastrointestinal, genitourinary, and sexual function were assessed
      retrospectively using a patient self-scoring, five-grade toxicity scale. Seven
      clinical and 15 technical variables were recorded for each patient. The
      association between the clinical and technical variables and rectal, bladder, and
      sexual side effects was examined. The 375 patients who received small-field
      (<12.5 x 12.5-cm) external beam irradiation via a four-field box on a 6-MV (n =
      74, or 20% of patients), 8-MV (n = 140, or 37%), or 15-MV (n = 161, or 43%)
      linear accelerator form the basis for the study. Ninety-one percent of patients
      received treatment with 1.8-2.0 Gy fractions to a delivered dose of at least 66
      Gy. Follow-up was complete through 62 months in living patients, with five (1%)
      of the entire group lost to follow-up. RESULTS: A total of 137 of 354 evaluable
      patients (39%) reported rectal complications after treatment; however, 20
      patients(6%) had heme-positive stools as their only symptom and 66 (19%) had mild
      symptoms not requiring treatment. Only 14% of the entire group required
      intervention. Of 356 patients, 117 (33%) evaluable for bladder complications
      developed genitourinary changes: In 14 patients (4%) asymptomatic hematuria
      occurred, 71 (20%) had mild symptoms not requiring treatment, and 32 (9%)
      required treatment. Of the 171 patients who were potent prior to radiation, 106
      (62%) reported impotence after treatment. No statistically significant
      association was identified between any clinical or technical variables (including
      machine energy) assessed and complications. CONCLUSIONS: In this retrospective
      review, treatment-related bowel and bladder side effects were not identified in
      the majority of patients despite the use of a grading system designed to identify
      subtle changes. Impotence, however, was common. Although pretreatment clinical
      characteristics varied among patients, they could not be used to predict the
      subsequent development of complications. The only treatment-related
      characteristic that varied in this study was machine energy, which did not
      correlate with complications.

PMID- 9607339
TI  - Clinical course of rectal bleeding following I-125 prostate brachytherapy.
AB  - PURPOSE: Despite the occurrence of some rectal complications in most large series
      of patients treated with radiation, there is surprisingly little information
      regarding their management. We report here the clinical course of such patients
      after I-125 brachytherapy, in an effort to help delineate a rational management
      policy. METHODS AND MATERIALS: 109 patients with stage T1 to T2 prostatic
      carcinoma and Gleason score 2 to 7 were treated with I-125 implantation from 1988
      through 1995. No external radiation was given. The prescribed minimum radiation
      dose to the prostate was 140 to 160 Gy. RESULTS: Nineteen of 109 patients
      (actuarial incidence: 19%) developed persistent, bright red rectal bleeding, from
      1 to 28 months following I-125 implantation. Most occurred in the early part of
      the implant experience. Bleeding resolved in 6 of the 19 patients, from 9 to 48
      months from the time of onset. Nine patients were treated with steroid enemas.
      Laser coagulation was used in three patients, and six patients had no
      intervention. There was no obvious difference in the resolution rate between
      groups. There was no obvious difference in the rectal wall radiation for patients
      who did or did not experience resolution of their bleeding. CONCLUSION:
      Persistent, minor radiation-related bleeding after prostate brachytherapy can be
      a source of consternation to patients. They should be reassured that spontaneous
      healing is likely to occur eventually in a large portion of patients, and should
      be cautioned against invasive treatment, unless absolutely necessary.

PMID- 9607340
TI  - The correlation between the ASTRO Consensus Panel definition of biochemical
      failure and clinical outcome for patients with prostate cancer treated with
      external beam irradiation. American Society of Therapeutic Radiology and
      Oncology.
AB  - PURPOSE: We reviewed our institution's experience treating patients with external
      beam irradiation (RT) to determine if the ASTRO Consensus Panel definition of
      biochemical failure (BF) following radiation therapy correlates with clinical
      distant metastases free survival (DMFS), disease-free survival (DFS), cause
      specific survival (CSS), and local control (LC). METHODS AND MATERIALS: Between
      1/1/87 and 12/31/92, 568 patients with clinically localized prostate cancer
      received external beam irradiation (RT) using localized prostate fields at
      William Beaumont Hospital (median total dose 66.6 Gy; range: 60-70.4 Gy).
      Biochemical failure was defined as three consecutive increases in post-treatment
      prostate specific antigen (PSA) after achieving a nadir. Biochemical failure was
      recorded as the time midway between the nadir and the first rising PSA. Five-year
      actuarial rates of clinical DMFS, DFS, CSS, and LC were calculated for patients
      who were biochemically controlled (BC) versus those who failed biochemically.
      Median follow-up was 56 months (range: 24-118 months). RESULTS: Five-year
      actuarial rates of DMFS, DFS, CSS, and LC were significantly greater in patients
      who were biochemically controlled versus those who were not (p < 0.001). In
      patients who were BC, the 5-year actuarial rates of DMFS, DFS, CSS, and LC were
      99%, 99%, 98%, and 99% respectively. For patients who failed biochemically, the 5
      year actuarial rates of DMFS, DFS, CSS, and LC were 74%, 64%, 89%, and 86%
      respectively. When stratifying by pretreatment PSA, Gleason score, and T stage
      these differences remained significant for DMFS, DFS, and CSS. The Cox
      proportional hazards model demonstrated that BC was the single most important
      predictor of clinical outcome for DMFS, DFS, CSS, and LC. Pretreatment PSA and
      Gleason score were also independent predictors of outcome for DMFS and DFS.
      CONCLUSIONS: The ASTRO Consensus Panel definition of BF following radiation
      therapy correlates well with clinical DMFS, DFS, and CSS. These findings suggest
      that the Consensus Panel definition may be a surrogate for clinical progression
      and survival and should be considered a valid endpoint for separating successful
      versus unsuccessful treatment. Additional studies with longer follow-up will be
      needed to corroborate these findings.

PMID- 9607341
TI  - Invasive bladder cancer: our experience with bladder sparing approach.
AB  - PURPOSE: Muscle-invasive bladder cancer (MIBC) is a disease associated with
      several unresolved therapeutic questions. Radical cystectomy still represents the
      most frequent treatment approach. The aim of our study was to evaluate the effect
      and feasibility of bladder-sparing treatment by transurethral resection (TUR) and
      sequential chemoradiotherapy in patients with biopsy-proven invasive bladder
      cancer. METHODS AND MATERIALS: After maximal TUR, 105 patients were treated with
      two to four cycles of methotrexate, cisplatinum, and vinblastine
      polychemotherapy. In complete responders, the treatment was continued by
      radiotherapy (50 Gy to the bladder and 40 Gy to the regional lymph nodes),
      whereas in nonresponders, cystectomy was performed when feasible. RESULTS:
      Complete response after TUR and chemotherapy was achieved in 52% of patients.
      After a median follow-up of 42 months, 52 of 75 patients (69%) selected for
      bladder preservation were without evidence of disease in the bladder. Freedom
      from local failure in complete responders to chemotherapy was 80% [95% confidence
      interval (CI), 69-91%) at 4 years. The actuarial survival of the entire group was
      58% (95% CI, 47-69%), whereas the survival rate with the bladder intact was 45%
      (95% CI, 34-56%) at 4 years. Survival was significantly better in patients who
      responded to chemotherapy (79%) than in nonresponders (35%, p < 0.0001). There
      was no significant difference in survival between nonresponders who underwent
      cystectomy and nonresponders who completed treatment with radiotherapy
      (approximately 30% at 3 years). CONCLUSION: The present study confirms that MIBC
      is a heterogeneous disease, and that in more than half of patients who are
      affected, a bladder-sparing approach is safe. Our study has also demonstrated
      that in nonresponders, radical cystectomy as the treatment of choice is
      questionable.

PMID- 9607342
TI  - Factors influencing the development of lung fibrosis after chemoradiation for
      small cell carcinoma of the lung: evidence for inherent interindividual
      variation.
AB  - PURPOSE: Clinical observations often reveal individual differences in the
      severity of lung fibrosis after definitive radiation therapy for lung cancer.
      Recent experimental studies suggest that the risk of developing lung fibrosis may
      be genetically controlled. The present study was undertaken to examine the
      magnitude of individual variation in the incidence and severity of lung fibrosis
      in a well-defined patient population treated by concurrent chemoradiation for
      limited small-cell lung carcinomas (LSCLC). MATERIALS AND METHODS: Between 1989
      and 1994, 56 patients with LSCLC were enrolled in one of two controlled
      prospective studies of concurrent chemotherapy and concomitant conventional (45
      Gy in 25 fractions q.d. over 5 weeks) or accelerated (45 Gy in 30 fractions
      b.i.d. over 3 weeks) radiotherapy. Chemotherapy consisted of cisplatin and
      etoposide (PE) or PE plus ifosfamide and mesna (PIE). Of the 56, a group of 25
      patients who had serial computerized tomography (CT) examinations of the chest
      and were deemed to have unequivocal radiographic complete responses were selected
      for this study. The severity of lung fibrosis was recorded for each patient from
      the CT images using an arbitrary scale (0 to 3) at 1 year after treatment.
      Radiographic fibrosis scores were recorded on 1-3 CT slices in 3 different dose
      areas (20-30 Gy; 30-40 Gy; and >40 Gy) that were defined using the corresponding
      CT slices from the patient's CT treatment plan. Of these patients, 23 (92%) had
      at least 2 slices scored; 11 patients had all 3 slices scored. RESULTS: Among the
      clinical and treatment parameters investigated (including type of chemotherapy),
      only total dose and fractionation schedule were identified as significant and
      independent determinants of lung fibrosis. Radiographic fibrosis scores were
      higher in high-dose areas and among patients treated with the accelerated
      schedule. Using a fit of the proportional odds (PO) model based on the total dose
      and fractionation schedule, fibrosis score residuals were calculated for each
      patient. The residual for each score is defined as the difference between the
      observed and expected score based on the dose and treatment schedule received.
      Average residuals varied significantly among patients (p = 0.005, Kruskal-Willis
      test). Using a modified version of the PO model, the coefficient of variation in
      patient heterogeneity was estimated to be 10.1% (95% confidence interval: 6.2
      14.9%). Inclusion of the heterogeneity factor, in addition to total dose and
      fractionation schedule, improved the fit of the PO model to an extremely high
      level of significance (p < 10(-7)). CONCLUSIONS: Our data indicate that the risk
      and severity of lung fibrosis analyzed radiographically on CT images increases
      with total dose and with the use of an accelerated radiation schedule, for
      patients treated with chemoradiation for small-cell lung cancer. There was also
      demonstrable patient-to-patient heterogeneity, suggesting that the risk of lung
      fibrosis is strongly affected by inherent factors that vary among individuals.

PMID- 9607343
TI  - Effect of low-dose chest irradiation before chemotherapy on the rate of local
      failure in small-cell lung cancer.
AB  - PURPOSE: To evaluate the rate of tumor recurrence within the irradiated volume
      after initial low-dose irradiation of limited-stage small-cell lung cancer
      (SCLC), to assess the tolerance of a sequential combination of low-dose chest
      irradiation followed by chemotherapy, and to confirm the responsiveness of
      limited-stage SCLC to low-dose irradiation. METHODS AND MATERIALS: In this pilot
      study, 26 patients with limited-stage SCLC were treated by first-line 20-Gy
      thoracic irradiation followed 3 weeks later by chemotherapy (cisplatin,
      doxorubicin, and etoposide for six cycles). RESULTS: We present our final results
      with a median follow-up of surviving patients of 7 years. The response rate to
      this low-dose irradiation was 83%, with an overall response rate to
      radiochemotherapy of 96% and a median survival of 21 months. No unexpected early
      or late toxicity was observed. The rate of initial isolated local failure was 8%,
      which compares favorably with other published series using higher doses of
      radiochemotherapy. CONCLUSION: An initial chest irradiation of 20 Gy before
      chemotherapy could be sufficient to reduce the risk of local failure during the
      time of survival of patients with limited-stage SCLC. Potential advantages of
      this treatment may be the prevention of resistance mechanisms to radiotherapy
      induced by preliminary chemotherapy and a reduced radiation-induced toxicity.

PMID- 9607344
TI  - The effect of radiotherapy on the survival of non-small cell lung cancer
      patients.
AB  - PURPOSE: To determine if thoracic radiotherapy improves the survival of non-small
      cell lung cancer (NSCLC) patients. METHODS AND MATERIALS: A Cox proportional
      hazards model with prognostic and treatment covariates was estimated using
      prospective data for 129 NSCLC patients presenting at the Victoria Clinic (ViCC)
      of the British Columbia Cancer Agency (BCCA) 1990-1991. The estimated model was
      simulated to predict survival curves for groups of patients with and without
      treatment. The difference between the predicted median survival with treatment
      and without treatment is the gain in survival attributable to treatment. RESULTS:
      After adjusting for the effect of TNM staging, Karnofsky performance status,
      weight loss, tumor size, and tumor histology on survival, high-dose palliative
      radiotherapy (RT) (30-50 Gy in 10-20 fractions) increased median survival by 79
      days (95% confidence interval: 31-106 days), and lowered the relative risk of
      death rate to 0.53 (95% confidence interval: 0.35-0.85). Radical RT (50 or more
      Gy, in 20 or more fractions) increased median survival by 424 days (95%
      confidence interval: 302-488 days), and lowered the relative risk of death to
      0.24 (95% confidence interval: 0.14-0.43). CONCLUSION: Our results support the
      hypothesis that the increased survival of patients receiving aggressive
      palliative, or radical, RT is due not solely to patient selection, but also
      partly to a response to treatment.

PMID- 9607345
TI  - Role of radiation therapy in the treatment of primary tracheal carcinoma.
AB  - PURPOSE: The objective of this work is to investigate the role of radiation
      therapy in the treatment of primary tracheal carcinoma. METHODS AND MATERIALS:
      From 1963 to 1993, 106 patients presenting with a tracheal carcinoma received a
      radiation course as part of their treatment in three institutions. Eighty-four
      patients were treated with megavoltage radiation only, receiving doses ranging
      from 30 to 70 Gy, with a median dose of 56 Gy. Five patients received high-dose
      rate (HDR) brachytherapy, five patients underwent a surgical procedure, and eight
      received chemotherapy. RESULTS: With a mean follow-up of 141 months, the overall
      1-, 2-, and 5-year survival rates are 46%, 21%, and 8%, respectively. Prognostic
      factors included tumor size (less than 3 cm), performance status, and total
      radiation dose: the 5-year survival rate dropped from 12% for patients receiving
      doses greater than 56 Gy to 5% for lower doses. Performance status and radiation
      doses are the only independent significant factors in multivariate analysis;
      these results must however be analyzed with precaution in this retrospective
      study. CONCLUSIONS: Radiation is a good alternative to surgery for primary
      tracheal cancer. A review of the literature and our current results allow us to
      recommend a radiation dose greater than 60 Gy for primary irradiation.
      Collaborative studies are warranted to (1) determine the optimal radiation dose
      for definitive irradiation, (2) define the potential role of radiation after
      complete and partial surgery, (3) determine the role and optimal treatment scheme
      for HDR brachytherapy, (4) describe and record the late effects, (5) establish
      the potential benefit of chemoradiation.

PMID- 9607346
TI  - Tumor size, irradiation dose, and long-term outcome of carcinoma of uterine
      cervix.
AB  - PURPOSE: To assess the impact of tumor size and extent, and dose of irradiation
      on pelvic tumor control, incidence of distant metastases, and disease-free
      survival in carcinoma of the uterine cervix. METHODS AND MATERIALS: Records were
      reviewed of 1499 patients (Stages IA-IVA) treated with definitive irradiation
      (combination of external beam plus two intracavitary insertions to deliver doses
      of 65-95 Gy to point A, depending on stage and tumor volume). Follow-up was
      obtained in 98% of patients (median 11 years, minimum 3 years, maximum 30 years).
      The relationship between outcome and tumor size was analyzed in each stage.
      Pelvic tumor control was correlated with total doses to point A and to the
      lateral pelvic wall. RESULTS: The 10-year actuarial pelvic failure rate in Stage
      IB was 5% for tumors <2 cm, 15% for 2.1-5 cm, and 35% for tumors >5 cm (p =
      0.01); in Stage IIA, the rates were 0%, 28%, and 25%, respectively (p = 0.12).
      Stage IIB unilateral or bilateral nonbulky tumors <5 cm had a 23% pelvic failure
      rate compared with 34% for unilateral or bilateral bulky tumors >5 cm (p = 0.13).
      In Stage IIB, pelvic failures were 18% with medial parametrial involvement only,
      compared with 28% when tumor extended into the lateral parametrium (p = 0.05). In
      Stage III, unilateral parametrial involvement was associated with a 32% pelvic
      failure rate versus 50% for bilateral extension (p < 0.01). Ten-year disease-free
      survival rates were 90% for IB tumors <2 cm, 76% for 2.1-4 cm, 61% for 4.1-5 cm,
      and 47% for >5 cm (p = 0.01); in Stage IIA, the rates were 93%, 63%, 39%, and
      59%, respectively (p < or = 0.01). Patients with Stage IIB medial parametrial
      involvement had better 10-year disease-free survival (67%) than those with
      lateral parametrial extension (56%) (p = 0.02). Stage III patients with
      unilateral tumor extension had a 48% 10-year disease-free survival rate compared
      with 32% for bilateral parametrial involvement (p < or = 0.01). The presence of
      endometrial extension or tumor only in the endometrial curettings had no
      significant impact on pelvic failure. However, in patients with Stage IB disease,
      the incidence of distant metastases was 31% with positive curettings, 15% with
      negative curettings, and 22% with admixture (p < or = 0.01). In Stage IIA, the
      corresponding values were 51%, 33%, and 18% (p = 0.05). The 10-year disease-free
      survival rates in Stage IB were 67% with positive curettings, 81% for negative
      curettings, and 77% for admixture (p = 0.02); in Stage IIA, the rates were 45%,
      66%, and 67%, respectively (p = 0.14). Because this is not a prospective Phase II
      dose-escalation study, the correlation of doses of irradiation with pelvic tumor
      control in the various stages and tumor size groups is not consistent.
      Nevertheless, with Stage IB and IIA tumors <2 cm in diameter, the pelvic failure
      rate was under 10% with doses of 70-80 Gy to point A, whereas for larger lesions
      even doses of 85-90 Gy resulted in 25% to 37% pelvic failure rates. In Stage IIB
      with doses of 70 Gy to point A, the pelvic failure rate was about 50% compared
      with about 20% in nonbulky and 30% in bulky tumors with doses > 80 Gy. In Stage
      III unilateral lesions, the pelvic failure rate was about 50% with < or =70 Gy to
      point A versus 35% with higher doses, and in bilateral or bulky tumors it was 60%
      with doses <70 Gy and 50% with higher doses. CONCLUSIONS: Clinical stage and size
      of tumor are critical factors in prognosis, therapy efficacy, and evaluation of
      results in carcinoma of the uterine cervix. The doses to point A suggest that for
      lesions <2 cm, doses of 75 Gy result in < or =10% pelvic failures, whereas in
      more extensive lesions, even with doses of 85 Gy, the pelvic failure rate is
      about 30%; and in Stage IIB-III tumors, doses of 85 Gy result in 35-50% pelvic
      failures. Refinements in brachytherapy techniques and/or use of agents to
      selectively sensitize the tumors to irradiation will be necessary to improve the
      present results in invasive carcinoma of t

PMID- 9607347
TI  - Definitive radiotherapy combined with high-dose-rate brachytherapy for Stage III
      carcinoma of the uterine cervix: retrospective analysis of prognostic factors
      concerning patient characteristics and treatment parameters.
AB  - PURPOSE: To assess treatment outcome after definitive radiotherapy for Stage III
      cervical carcinoma retrospective analysis of the clinical data was performed.
      METHODS AND MATERIALS: We enrolled 265 patients with Stage III cervical carcinoma
      who were treated with combined external beam radiotherapy [mean +/- standard
      deviation (SD), 50.3 +/- 1.8 Gy; range 40-70) and intracavitary brachytherapy
      (ICBT) (mean +/- SD, 19.8 +/- 2.4 Gy; range 10-32) using a high-dose-rate 60Co
      source. We retrospectively analyzed, as measures of the therapeutic outcome, the
      overall survival rate (OAS), relapse-free survival rate (RFS), locoregional event
      free rate (LREF), distant metastasis (DM), and late complication. RESULTS: The 5
      year OAS, RFS, and LREF rates (n = 265) were 50.7%, 57.1%, and 71.2%,
      respectively. Univariate analysis revealed a significant favorable effect on the
      OAS rate for complete response (CR) (p = 0.024), maximum tumor diameter < 6 cm
      (SML) (p = 0.0009), Karnofsky performance score > or =70 (p = 0.046), age <75
      years (p = 0.0043), hemoglobin (Hb) concentration of > or =9 g/dl (p = 0.0005),
      and histopathological diagnosis of squamous cell carcinoma (SCC) (p = 0.0089). In
      the multivariate analysis, Hb, SCC, SML, and CR remained significant prognostic
      factors. In both univariate and multivariate analysis, SML, Hb, age, and SCC
      showed significant effects on the RFS rate. Age > or =60 years (p = 0.017), Hb >
      or =9 g/dl (p = 0.0039), and SML (p = 0.0046) were significant favorable
      prognostic factors for the LREF rate identified by univariate analysis. In
      addition, advanced age, SML, and SCC showed significant beneficial effects on the
      LREF rate in the multivariate analysis. DM developed in 21.1% of patients, and
      the groups with Hb < 9 g/dl (p < 0.005), Karnofsky performance score of <70 (p <
      0.001), and dose at point A in the ICBT < 16 Gy (p < 0.005) developed a
      significantly greater incidence of DM than did the groups without. The 5-year
      incidence was 2.6% for major bladder complication and 8.3% for major rectal
      complication. The radiation dose in the subgroup with rectal complication was
      significantly greater than that in the subgroup without complications.
      CONCLUSION: In patients with Stage III cervical carcinoma, tumor size,
      concentration of Hb, and histopathological diagnosis are strong prognostic
      factors for the therapeutic outcome. The ICBT dose in our study was small
      compared to the reported data, but the outcome was quite comparable. Thus, the
      dose we used might be the minimum required. However, locoregional control still
      remains an important problem. It is necessary to attain the optimal dose
      distribution in both the target volume and in critical organs. In high-risk
      patients, combined use of chemotherapy is crucial to improve the response to
      radiation.

PMID- 9607348
TI  - Late complications after postoperative radiotherapy in endometrial cancer:
      analysis of 317 consecutive cases with application of linear-quadratic model.
AB  - PURPOSE: To evaluate the incidence and risk factors for late complications after
      postoperative radiotherapy in endometrial cancer patients. METHODS AND MATERIAL:
      We performed a detailed retrospective analysis of 317 endometrial cancer patients
      given postoperative radiotherapy. A total of 247 patients (78%) received both
      intracavitary (BRT) and external beam irradiation (XRT); 49 patients (15%)
      received only BRT, and 21 (7%) only XRT. BRT included radium (Ra) and cesium
      (Cs). The mean dose rate for both isotopes at 0.5 cm from the applicator surface
      was 0.47 +/- 0.06 and 1.42 +/- 0.41 Gy/h, and the mean total dose was 50.5 +/-
      10.3 and 48.4 +/- 15.0 Gy, respectively. Mean BRT dose at 0.5 cm was 50.1 +/-
      11.7 Gy (range 14.5-71.0). Mean XRT dose in the International Commission on
      Radiation Units and Measurements (ICRU) reference point was 49.0 +/- 3.7 Gy
      (range 22.0-66.0) given in fractions of 1.54-2.49 Gy (mean 2.0 +/- 0.17) with a
      two- or four-field technique. Follow-up ranged from 4 to 21 years (median 7.3).
      Normalized total dose (NTD) including XRT and BRT doses was calculated based on a
      linear quadratic equation. RESULTS: Five-year overall survival rate was 75%, and
      5-year disease-free survival (censored for noncancer deaths) was 81%. Late
      radiotherapy complications of any grade occurred in 158 patients (51%), including
      bowel complications in 41% and urinary bladder complications in 21%. A total of
      37 grade 3 or 4 complications were observed in 33 patients (11%), of whom 32 were
      treated with both XRT and BRT. Severe bowel and/or urinary bladder complications
      occurred in 24 patients: in 14 of 72 patients (19.4%) who received XRT and Cs
      BRT, and in 10 of 172 patients (6.0%) applied XRT and Ra BRT. The higher
      proportion of severe bowel and/or bladder complications in the former group was
      due to the particularly frequent rate of these events (30.0%) in a subset of 47
      patients who received XRT combined with Cs BRT at the dose rate of 1.7 Gy/h and
      the total BRT dose of 60 Gy. Higher NTD, XRT fraction dose, BRT dose rate, Cs
      BRT, two-field XRT technique, short overall radiotherapy time, and older age were
      correlated with increased late-event risk in univariate analysis. Multivariate
      Cox analysis demonstrated that the independent risk factors for late bowel
      complications were NTD (p = 0.000) and BRT dose rate (p = 0.036), whereas for
      bladder complications they were BRT dose rate (p = 0.005) and XRT fraction dose
      (p = 0.041). Neither clinical factor (age, parity, prior abdominal surgery, FIGO
      stage, diabetes mellitus, or hypertension) nor the surgery-to-radiotherapy
      interval, nor overall radiotherapy time was independently associated with the
      risk of late bladder or bowel complications. CONCLUSIONS: The risk of late
      complications after postoperative radiotherapy in endometrial cancer depends
      mainly on treatment-related factors: NTD, BRT dose rate, and XRT fraction dose.
      The use of combined XRT and BRT increases the risk of late effects. NTD
      calculations including BRT dose rate and XRT fraction dose enable estimation of
      radiobiologically equivalent dose and can decrease the risk of mistakes when the
      radiotherapy regimen is changed.

PMID- 9607349
TI  - Artificial neural network model of survival in patients treated with irradiation
      with and without concurrent chemotherapy for advanced carcinoma of the head and
      neck.
AB  - PURPOSE: This study was performed to investigate the feasibility of predicting
      survival in squamous cell carcinoma of the head and neck (SCCHN) with an
      artificial neural network (ANN), and to compare ANN performance with conventional
      models. METHODS AND MATERIALS: Data were analyzed from a Phase III trial in which
      patients with locally advanced SCCHN received hyperfractionated irradiation with
      or without concurrent cisplatin and 5-fluorouracil. Of the 116 randomized
      patients, 95 who had 2-year follow-up and all required data were evaluated. ANN
      and logistic regression (LR) models were constructed to predict 2-year total
      survival using round-robin cross-validation. A modified staging model was also
      examined. RESULTS: The best LR model used tumor size, nodal stage, and race to
      predict survival. The best ANN used nodal stage, tumor size, stage, and
      resectability, and hemoglobin. Treatment type did not predict 2-year survival and
      was not included in either model. Using the respective best feature sets, the
      area under the receiver operating characteristic curve (Az) for the ANN was 0.78
      +/- 0.05, showing more accurate overall performance than LR (Az = 0.67 +/- 0.05,
      p = 0.07). At 70% sensitivity, the ANN was 72% specific, while LR was 54%
      specific (p = 0.08). At 70% specificity, the ANN was 72% sensitive, while LR was
      54% sensitive (p = 0.07). When both models used the five predictive variables
      best for an ANN, Az for LR decreased [Az = 0.61 +/- 0.06, p < 0.01 (ANN)]. The
      models performed equivalently when using the three variables best for LR. The
      best ANN also compared favorably with staging [Az = 0.60 +/- 0.07, p = 0.02
      (ANN)]. CONCLUSIONS: An ANN modeled 2-year survival in this data set more
      accurately than LR or staging models and employed predictive variables that could
      not be used by LR. Further work is planned to confirm these results on larger
      patient samples, examining longer follow-up to incorporate treatment type into
      the model.

PMID- 9607350
TI  - T1/T2 glottic cancer managed by external beam radiotherapy: the influence of
      pretreatment hemoglobin on local control.
AB  - PURPOSE: Pretreatment hemoglobin (Hb) level has been reported to be an important
      prognostic factor for local control and survival in various malignancies.
      However, in many settings, the adverse effect of a low Hb may be related to more
      advanced disease. The purpose of this analysis was to assess the influence of
      pretreatment Hb on local control in a large series of patients with a localized
      cancer (T1/T2 glottic cancer, AJCC 1992) treated in a standard fashion. MATERIALS
      AND METHODS: Between January 1981 and December 1989, 735 patients (median age 63;
      657 males, 78 females) with T1/T2 glottic cancer were treated with radiation
      therapy (RT). The standard RT prescription was 50 Gy in 20 fractions over 4 weeks
      (97% of patients). Factors studied for prognostic importance for local failure
      included pretreatment Hb, age, sex, T category, anterior commissure involvement,
      subglottic extension, and tumor bulk (presence of visible tumor vs. subclinical
      disease). RESULTS: With a median follow-up of 6.8 years (range 0.2-14.3), 131
      patients have locally relapsed for an actuarial 5-year relapse-free rate of
      81.7%. The 5-year actuarial survival was 75.8%. The mean pretreatment hemoglobin
      level was 14.8 g/dl and was similar in all prognostic categories. On multivariate
      analysis, using the Cox proportional hazards model, pretreatment Hb predicted for
      local failure after RT. The hazard ratio (HR) for relapse was calculated for
      various Hb levels. For example, the HR for a Hb of 12 g/dl vs. a Hb of 15 g/dl
      was 1.8 (95% confidence interval 1.2-2.5). Previously established factors,
      including gender, T category, subglottic extension, as well as tumor bulk, were
      also prognostically important for local control. CONCLUSIONS: This analysis, in a
      large number of similarly treated patients, indicates that pretreatment Hb is an
      independent prognostic factor for local control in patients with T1/T2 carcinoma
      of the glottis treated with RT. The underlying biology of this observation needs
      to be explored, and using this information, it may be possible to develop
      strategies to improve treatment outcome.

PMID- 9607351
TI  - Primary radiotherapy of carcinoma of the supraglottic larynx--a multivariate
      analysis of prognostic factors.
AB  - PURPOSE: The aim of this study was to analyze the importance of different
      possible prognostic factors in cancer of the supraglottic larynx. METHODS AND
      MATERIALS: Nine hundred thirty-two patients with carcinoma of the supraglottic
      larynx were consecutively treated at The Finseninstitute in Copenhagen between
      1966 and 1991. Of the patients, 768 treated with radiotherapy only were eligible
      for a multivariate Cox regression analysis of prognostic factors with local
      regional control as endpoint. Of these, 73% (561) were men and 27% (207) women.
      Twelve factors: Age; gender; tumor size; site; T category (UICC78); nodal
      involvement (UICC 78); stage (UICC78); treatment period; tumor surface
      appearance; histopathologic differentiation; cord mobility; and hemoglobin level
      were tested. RESULTS: Only gender, T, N, and size proved to have independent
      significant prognostic importance in the multivariate analysis. A hazard index
      including these four factors for each patient was calculated, and eight risk
      groups formed. When the relative risks (RR) for these groups were plotted against
      the corresponding 5-year local-regional control failure rates, a very simple
      equation for the risk of failure could be derived as: 5-year local failure risk =
      0.2 + 0.1 RR. CONCLUSION: We recommend that this estimation of an individual
      patient's risk of failure should be implemented in future clinical decision
      making.

PMID- 9607352
TI  - Ethmoid sinus cancer: twenty-nine cases managed with primary radiation therapy.
AB  - PURPOSE: To describe the outcome of patients with carcinoma of the ethmoid sinus
      managed with a policy of primary radiation therapy with surgery for salvage of
      persistent or progressive disease. METHODS AND MATERIALS: A retrospective chart
      review was undertaken of 29 patients with the diagnosis of carcinoma of the
      ethmoid complex who underwent treatment in the period between January 1976 and
      December 1994 at the Princess Margaret Hospital. Analysis was confined to those
      patients with epithelial invasive histology (squamous carcinoma, adenocarcinoma,
      or undifferentiated carcinoma) managed with curative intent with primary
      radiation therapy. The median patient age was 62, with a median follow-up time of
      4 years. Staging was assigned according to a modification of the UICC 1997 system
      with 19 (66%) of patients presenting with T4 category tumors. The most common
      radiation dose regimes were 60 Gy in 30 daily fractions over 6 weeks, or 50 Gy in
      20 daily fractions over 4 weeks. Outcome was analyzed with respect to overall
      survival, cause-specific survival, and local progression-free survival. The
      influence of a variety of clinical and therapeutic factors on outcome is
      discussed, the patterns of disease failure are described, and the rationale for
      this treatment approach is outlined. RESULTS: The 5-year rates of overall
      survival, cause-specific survival, and local progression-free survival were 39%,
      58%, and 41%, respectively. A total of 18 of 29 patients died during the period
      of review. Of these, 12 deaths were due to ethmoid cancer, one was due to a
      second primary lung cancer, and five were attributed to nononcologic causes. No
      patients died due to treatment-related toxicity. Increasing T category predicted
      for worse outcome on univariate analysis. Local progression was the major cause
      of treatment failure and was documented in 15 of 29 patients treated (52%). Six
      patients were offered salvage surgery for local progression, of whom two remained
      disease free at 15 and 17 months follow-up. CONCLUSIONS: Outcome of patients with
      ethmoid cancer managed with primary radiation therapy with surgery for salvage is
      comparable to that achieved with planned combined modality approaches.
      Nevertheless, outcome remains poor and is dependent on the local extent of tumor,
      with 40-50% of patients eventually succumbing to disease.

PMID- 9607353
TI  - Adjuvant radiotherapy for squamous cell carcinoma of the tongue base: improved
      local-regional disease control compared with surgery alone.
AB  - PURPOSE: The purpose of this retrospective study is to present the results of
      postoperative adjuvant radiotherapy after primary surgery for squamous cell
      carcinoma of the tongue base and to compare these results to those obtained with
      surgery alone. METHODS: Between 1974 and 1993, continuous-course postoperative
      radiotherapy was delivered to 24 patients (Adjuvant Radiotherapy Group). Results
      were compared to those from a group of 55 patients treated with surgery alone
      (Surgery Group). RESULTS: Characteristics of the two groups were similar, except
      that a larger proportion of patients in the Adjuvant Radiotherapy Group had
      higher pathologic TNM stages. Ipsilateral neck control (87% vs. 68%, p = 0.04),
      contralateral neck control (100% vs. 76%,p = 0.002), relapse-free survival (64%
      vs. 46%,p = 0.04), and control above the clavicles (80% vs. 48%, p = 0.007) were
      significantly higher in the Adjuvant Radiotherapy Group compared to those in the
      Surgery Group (5-year figures shown). CONCLUSION: The use of adjuvant
      radiotherapy after surgical resection of tongue base squamous cell carcinoma
      significantly decreased the rate of local-regional recurrence and improved
      relapse-free survival compared with surgery alone but did not alter cause
      specific or overall survival.

PMID- 9607354
TI  - Locally recurrent nasopharyngeal carcinoma: treatment results for patients with
      computed tomography assessment.
AB  - PURPOSE: To study the treatment outcome in patients with locally recurrent
      nasopharyngeal carcinoma as restaged by computed tomography (CT). PATIENTS AND
      METHODS: One hundred forty patients with CT restaged locally recurrent
      nasopharyngeal carcinoma were reviewed. Patients were restaged at recurrence
      according to the AJCC stage classification with the following distribution: T1
      T2:30%, T3:19%, T4:51%. Ninety-seven patients received reirradiation; among these
      62 had external irradiation, 34 had brachytherapy, and 1 had both. Twelve
      patients received surgery. Thirty-one patients were treated with palliative
      intent and received either chemotherapy or supportive treatment only. Overall
      survival (OAS) and performance-adjusted survival (PAS, defined as surviving with
      a Karnofsky performance score [KPS] > 50) were calculated by Kaplan-Meier method.
      Multivariate analysis was performed using the Cox model. RESULTS: The median
      survival for all patients was 23.8 months. After reirradiation, the 3-yr and 5-yr
      OAS rates were 46% and 36%, respectively. The corresponding PAS rates were 40%
      and 28%. The 3-yr OAS rates for recurrent T1-2, T3, and T4 disease after
      reirradiation were 71%, 42%, and 30%; the corresponding 5-yr OAS rates were 57%,
      42%, 17%. The 3-yr and 5-yr OAS rates in patients receiving palliative treatments
      only were 19% and 0%, respectively. The 3-yr OAS rate after surgery was 42%. In
      the multivariate analysis, older age, recurrent T3-4 disease, and palliative
      treatment were unfavorable factors in predicting overall survival, whereas
      recurrent T3-4 disease, baseline KPS < 70, and palliative treatment were
      unfavorable factors in predicting PAS. A high complication rate was observed
      after reirradiation, with 34% of patients developing neurological sequel.
      CONCLUSION: Aggressive treatment for locally recurrent nasopharyngeal carcinoma
      is warranted especially for those with disease confined to the nasopharynx.
      Survival after retreatment for more extensive disease remains poor but was still
      superior to supportive treatment only. Early diagnosis of local recurrence allows
      prompt administration of treatment and is associated with better outcome. Future
      studies should aim at improving the therapeutic ratio in the retreatment of
      recurrent disease especially in patients with more extensive local recurrence.

PMID- 9607355
TI  - Stereotactic radiosurgery for chordoma and chondrosarcoma: further experiences.
AB  - PURPOSE: Skull base chordomas and chondrosarcomas pose management challenges
      owing to their critical location, locally aggressive nature, and high recurrence
      rate despite multimodality treatment. We used stereotactic radiosurgery as
      primary or adjuvant therapy to achieve safe and effective therapeutic
      irradiation. METHODS AND MATERIALS: At an average of 4 years (range 1-7), we
      evaluated 15 patients (nine with chordomas and six with chondrosarcomas) who had
      gamma-knife radiosurgery as an adjunct (13 patients) or as an alternative to
      microsurgical resection (two patients). Patient age varied from 7 to 70 years
      (mean 38). There was a distinct male preponderance (2:1). Thirteen patients had
      undergone between one and four resections. Using conformal radiosurgical
      planning, a maximum tumor dose of 24-40 Gy (mean 36) and a tumor margin dose of
      12-20 Gy (mean 18) was given to a mean tumor volume of 4.6 ml. RESULTS: Eight
      patients showed clinical improvement, three remained stable, and four died. Two
      of the four patients who died had tumor progression remote from the radiosurgery
      volume; two patients died of unrelated disorders. Among 11 surviving patients,
      follow-up imaging showed a reduction in tumor size in five, no further tumor
      growth in five, and an increase in the size of the tumor in one. The patient with
      further tumor growth after radiosurgery subsequently underwent repeat resection.
      CONCLUSION: Despite the formidable management challenge posed by these neoplasms,
      our long-term evaluation has shown that radiosurgery is a safe and effective
      treatment for patients with small volume tumors.

PMID- 9607356
TI  - Prognostic value of CA 19-9 levels in patients with carcinoma of the pancreas
      treated with radiotherapy.
AB  - PURPOSE: CA 19-9 has been identified as a tumor marker for pancreatic carcinoma
      and has been shown to have some utility in predicting outcome in surgically
      treated patients. The purpose of this study was to evaluate its usefulness as a
      prognostic indicator in patients treated with radiotherapy. MATERIALS AND
      METHODS: A retrospective review of all patients treated with radiotherapy of
      definitive intent (n = 104) for carcinoma of the pancreas at Fox Chase Cancer
      Center from 1980-1994 was undertaken. Patients were categorized into four groups:
      Planned preoperative radiation with resection (n = 25); planned preoperative
      radiation without successful resection (n = 35); postoperative radiation (n =
      21); and radiation without planned resection (n = 23). For each group, except
      those treated without planned resection, median dose for external beam
      radiotherapy was 50.4 Gy (range = 21.6-63.0 Gy). Those in the remaining fourth
      group were treated with a median dose of 55.8 Gy (range = 36.0-60.4 Gy). 97% of
      patients in the first three groups were also treated with 5-FU-based
      chemotherapy, as were 61% of those in the fourth group. Pretreatment and follow
      up CA 19-9 levels were available for 69 patients. RESULTS: Median survival time
      for all groups was 10 months (range = 1-67 months). Univariate analysis showed
      significant differences in survival among the groups: Preop with resection 22
      months; preop without resection 10 months, postop 17 months; and without planned
      resection 12 months (p = 0.0005). Overall, patients who underwent resection had a
      median survival time of 19 months, compared to 11 months in those who did not (p
      = 0.0006). CA 19-9 level at diagnosis was found to be a significant prognostic
      indicator on univariate analysis, with a median survival time of 8 months in
      those having a level greater than the median of 680 U/ml, compared to 20 months
      in those who did not (p = 0.0003). Similarly, the posttreatment nadir was
      significant, with a median survival time of 11 months in those with levels above
      the median of 162.5 U/ml, vs. 26 months in those with levels below 162.5 U/ml (p
      = 0.001). The median survival time for patients whose CA 19-9 levels decreased in
      response to treatment by more than 75% was 23 months (range = 6-34 months) vs. 8
      months (range = 3-21) in those with 75% or less response (p = 0.003). On stepwise
      multivariate analysis, pretreatment CA 19-9 level was found to be a significant
      predictor of survival (p = 0.005). Other potential indicators of outcome,
      including age, gender, KPS, prediagnosis weight loss, location of tumor, clinical
      TNM staging, size of lesion, vascular involvement on angiography, and sequence of
      radiation with respect to resection, were evaluated and were not found to be
      significant. CONCLUSION: CA 19-9 was demonstrated to be a useful prognostic
      indicator in patients treated with radiotherapy; other, more traditional,
      indicators of outcome were of less utility.

PMID- 9607357
TI  - Long-term follow-up of a randomized trial on adjuvant chemotherapy and hormonal
      therapy in locally advanced breast cancer.
AB  - PURPOSE: To study the effects on survival, disease-free survival, and
      locoregional control of adjuvant hormonal and chemotherapy in patients with
      locally advanced breast cancer after a minimal follow-up period of 14 years.
      METHODS AND MATERIALS: A total of 118 patients were randomized between
      radiotherapy alone (arm I); radiotherapy, 12 courses of cyclophosphamide,
      methotrexate, and 5-fluorouracil (CMF), and tamoxifen (arm II); adriamycine,
      vincristine (AV) alternated with CMF, then radiotherapy, followed by four cycles
      of chemotherapy (AV/CMF); and tamoxifen during the entire treatment period (arm
      III). RESULTS: No improvement in survival, disease-free survival, or locoregional
      control was observed. After 6 years of follow-up, the overall survival curves
      grew apart, resulting in differences in 10-year survival rates: 15% (confidence
      interval-3%, 33%) between arms III and I. CONCLUSION: Owing to the relatively
      small numbers of patients involved, the relative value of the three treatment
      modalities cannot be established completely.

PMID- 9607358
TI  - Radiotherapy for metastatic carcinomas of the kidney or melanomas: an analysis
      using palliative end points.
AB  - PURPOSE: To assess the rate and duration of response to palliative radiotherapy
      (RT) in patients with metastatic melanoma or renal cell carcinoma. PATIENTS AND
      METHODS: From 1992 to 1995, 90 patients were entered into a nonrandomized study.
      Goals of palliative RT were prospectively defined and subjective response was
      documented at the end of RT, after 2-6 weeks, and every 3 months thereafter. Most
      patients were treated with 5 x 4 Gy or 10 x 3 Gy. RESULTS: Relief of pain from
      bone lesions was observed in 26 of 40 cases, with a duration of response of 2.4
      months, corresponding to 57% of the remaining lifetime. A total of 55% of
      patients with persistent neurologic dysfunction despite corticosteroids improved,
      for a duration of 2.5 months (86% of the further lifespan). Freedom from symptoms
      in patients treated for impending neurological complications from metastases to
      the brain, spine, or nerve plexus was documented for 86-100% of their lifetime.
      CONCLUSIONS: Despite the methodological flaws discussed, the efficacy of a short
      course of palliative RT for so-called radioresistant tumors is demonstrated.

PMID- 9607359
TI  - Experiences of 23 patients > or = 90 years of age treated with radiation therapy.
AB  - PURPOSE: To present 23 patients > or = 90 years old treated with radiotherapy,
      and to retrospectively evaluate the results of radiotherapy and tolerance in
      these patients. METHODS AND MATERIALS: The clinical records of 27 patients over
      90 years of age who were treated with radiotherapy at the Department of
      Radiology, Shinshu University Hospital, and eight affiliated general hospitals
      from 1990 until 1995 were reviewed. The strategy of radiotherapy was individually
      planned depending on the stage of the disease and performance status (PS) of the
      patient; however, it was not modified, based solely on chronologic age. The
      overall survival rate and disease-free survival rate were determined using the
      Kaplan-Meier method. The Radiation Therapy Oncology Group scoring criteria of
      acute and late reactions of radiation therapy were used. RESULTS: This group of
      patients accounted for 0.37% of all patients treated with radiotherapy in these
      hospitals. Of these, 23 patients in whom cancer was pathologically confirmed and
      whose follow-up data were available for retrospective analysis were included in
      the final evaluation of data. The age of the 23 patients ranged from 90 to 96
      years (median 93). Tumor was untreated and in the early stage in five patients,
      locoregionally advanced in 13, recurrent in four, and systemic in one. Definitive
      radiation therapy was administered in 12 patients (13 sites), preoperative intent
      in one, and palliative intent in 10. The period of observation ranged from 2.5 to
      6 years (median 18 months). Seven patients were alive for 15-67 months. Fourteen
      patients died because of intercurrent diseases or senility associated with active
      cancer, and two because of senility without evidence of cancer. The overall and
      relapse-free survival rates were 65% and 30% at 1 year and 30% and 21% at 2
      years, respectively. Definitive radiation therapy was completed in 13 of 13
      patients (100%), and local control was attained in 9 of 13 patients at 6 months
      (62%). Palliative radiation therapy was completed as intended in 7 of 11 (64%),
      and effects of palliation were observed in 9 of 11 patients (81%). Acute
      dermatitis, mucositis, pharyngitis, esophagitis, and cystitis of grade 2-3
      related to the definitive radiation therapy were tolerable for the patients with
      good PS. It took 3-7 weeks (median 5) for acute moist desquamation of six lesions
      of skin cancer to heal. Depending on the radiation doses, grade 1-2 atrophy of
      skin and telangiectasia were documented for eight patients followed up for more
      than 1 year. A brief description of representative case is presented. CONCLUSION:
      Patients older than 90 years with good PS may tolerate the acute effects of
      radiotherapy administered according to conventional fractionation schedules.
      Definitive radiation therapy should be considered, when applicable, even for
      patients older than 90 years.

PMID- 9607360
TI  - Expression of p53, p21/WAF/CIP, Bcl-2, Bax, Bcl-x, and Bak in radiation-induced
      apoptosis in testicular germ cell tumor lines.
AB  - PURPOSE: Testicular germ cell tumors (TGCTs) represent one of the few tumor types
      that are curable by antineoplastic therapy, probably due to the high sensitivity
      of this neoplasm to induction of apoptosis by chemotherapeutic agents and/or
      ionizing radiation. Here, we tested cell susceptibility to radiation-induced
      apoptosis in a panel of TGCT cell lines and attempted to correlate this with the
      known potentially relevant molecular determinants (p53 gene status and Bcl-2
      family proteins) of apoptosis. METHODS AND MATERIALS: Induction of apoptosis by
      gamma-radiation was morphologically recognized in NT2, NCCIT, S2, and 2102 EP
      using Hoechst/PI staining and additionally confirmed by Western blot analysis of
      PARP cleavage. The p53 gene status was estimated by sequence analysis. Expression
      of p21/WAF/CIP was determined by Northern blot analysis and immunoblotting was
      used to monitor p53, Bax, Bcl-2, Bcl-x, and Bak protein levels. In vitro colony
      formation was studied to establish clonogenic survival curves. RESULTS: NT2 and
      NCCIT appeared to be susceptible for radiation-induced apoptosis, contrasting
      2102 EP and S2 which were highly resistant. Sequence analysis showed that NT2,
      S2, and 2102 EP are homozygous for wild-type p53 (wtp53), whereas NCCIT contains
      mutant p53 (mtp53). NT2 and 2102 EP cells showed radiation-induced p53
      upregulation, while NCCIT (mtp53) and S2 (no p53 protein) cells did not.
      Consistently, gamma-radiation-induced DNA damage resulted in a p53-dependent
      transactivation of the p21/WAF/CIP gene in NT2 and 2102 EP, but not in mtp53
      containing NCCIT cells and p53 nonexpressing S2 cells. Constitutive expression of
      Bax, Bcl-2, Bcl-x, and Bak was not affected by radiation and showed no
      correlation with cell susceptibility to radiation-induced apoptosis. A
      discrepancy was found between apoptosis and reproductive death. CONCLUSIONS: The
      present study revealed that: i) the presence of wtp53 may not be absolutely
      required for the hypersensitivity for radiation-induced apoptosis in TGCT cell
      lines, ii) the molecular mechanism underlying the unique radiosensitivity was
      independent of the expression of Bcl-2 family proteins, and iii) cell
      susceptibility to apoptosis induction is not sufficiently informative to predict
      intrinsic radiosensitivity as determined by clonogenic survival.

PMID- 9607361
TI  - Targeted radiotherapy of multicell neuroblastoma spheroids with high specific
      activity [125I]meta-iodobenzylguanidine.
AB  - PURPOSE: Iodine-125 induces cell death by a mechanism similar to that of high
      linear energy transfer (high-LET) radiation. This study investigates the
      cytotoxicity of high-specific-activity [125I]meta-iodobenzylguanidine (125I-mIBG)
      in human SK-N-MC neuroblastoma cells grown as three-dimensional multicellular
      spheroids. MATERIALS AND METHODS: Spheroids were incubated with high-specific
      activity 125I-mIBG (6 mCi/microg, 1000 times that of the conventional specific
      activity used for autoradiography). Cytotoxicity was assessed by fluorescence
      viability markers and confocal microscopy for intact spheroids, fluorescence
      activated cell sorting and clonogenic assay, and clonogenic assays for dispersed
      whole spheroids. Distribution of radioactive mIBG was determined by quantitative
      light-microscope autoradiography of spheroid cryostat sections. Dose estimation
      was based on temporal knowledge of the retained radioactivity inside spheroids,
      and of the radiolabel's emission characteristics. Findings were compared with
      those of spheroids treated under the same conditions with 131I-mIBG, cold mIBG,
      and free iodine-125. RESULTS: 125I-mIBG exerted significant cell killing.
      Complete spheroids were eradicated when they were treated with 500 microCi of
      125I-mIBG, while those treated with 500 microCi or 1000 microCi of 131I-mIBG were
      not. The observed difference in cytotoxicity between treatments with 125I- and
      131I-mIBG could not be accounted for by the absorbed dose of spheroid alone. The
      peripheral, proliferating cell layer of the spheroids remained viable at the
      moderate radioactivity of 100 microCi for both isotopes. Cytotoxicity induced by
      125I-mIBG was quantitatively comparable by the peripheral rim thickness to that
      of 131I-mIBG at the dose of 100 microCi. The peripheral rim thickness decreased
      most significantly in the first 17 hours after initial treatment. There was no
      statistical decrease in the rim thickness identified afterwards for the second,
      third, and fourth days of incubation. CONCLUSION: The cytotoxic effect of high
      specific-activity 125I-mIBG appears to be comparable to, if not more efficient
      than that of conventionally used 131I-mIBG at the same level of total
      radioactivity. 125I-mIBG may improve the therapeutic index over that of 131I-mIBG
      in the clinical management of metastatic neuroblastoma due to the short range of
      Auger electrons.

PMID- 9607362
TI  - IRLED-based patient localization for linac radiosurgery.
AB  - PURPOSE: Currently, precise stereotactic radiosurgery delivery is possible with
      the Gamma Knife or floor-stand linear accelerator (linac) systems. Couch-mounted
      linac radiosurgery systems, while less expensive and more flexible than other
      radiosurgery delivery systems, have not demonstrated a comparable level of
      precision. This article reports on the development and testing of an optically
      guided positioning system designed to improve the precision of patient
      localization in couch-mounted linac radiosurgery systems. METHODS AND MATERIALS:
      The optically guided positioning system relies on detection of infrared light
      emitting diodes (IRLEDs) attached to a standard target positioner. The IRLEDs are
      monitored by a commercially available camera system that is interfaced to a
      personal computer. An IRLED reference is established at the center of
      stereotactic space, and the computer reports the current position of the IRLEDs
      relative to this reference position. Using this readout from the computer, the
      correct stereotactic coordinate can be set directly. RESULTS: Bench testing was
      performed to compare the accuracy of the optically guided system with that of a
      floor-stand system, that can be considered an absolute reference. This testing
      showed that coordinate localization using the IRLED system to track translations
      agreed with the absolute to within 0.1 +/- 0.1 mm. As rotations for noncoplanar
      couch angles were included, the inaccuracy was increased to 0.2 +/- 0.1 mm.
      CONCLUSIONS: IRLED technology improves the accuracy of patient localization
      relative to the linac isocenter in comparison with conventional couch-mounted
      systems. Further, the patient's position can be monitored in real time as the
      couch is rotated for all treatment angles. Thus, any errors introduced by couch
      inaccuracies can be detected and corrected.

PMID- 9607363
TI  - Comparative treatment planning between proton and x-ray therapy in esophageal
      cancer.
AB  - PURPOSE: Conformal treatment planning with megavoltage x-rays and protons for
      five patients with esophageal cancer has been studied in an attempt to determine
      if there are advantages of using protons instead of x-rays. METHODS AND
      MATERIALS: For each of the five patients, two different proton plans, one x-ray
      plan, and one mixed plan with x-rays and protons were made. A three-dimensional
      treatment planning system, TMS, was used. The evaluation of the different plans
      was made by applying the tumor control probability (TCP) model proposed by Nahum
      and Webb and the normal tissue complication (NTCP) model proposed by Lyman on the
      dose distributions in terms of dose-volume histograms (DVHs). RESULTS: The
      comparison shows advantages of using protons instead of x-rays for all five
      patients. The dose-limiting organs at risk are the spinal cord, the lungs, and
      the heart, but the proton plans also spare the kidneys better than the x-ray plan
      does. At 5% NTCP in any risk organ, the calculated mean TCP value for the five
      patients is increased by an average of 20%-units (from 2 to 23%-units) with the
      best proton plan compared with x-rays only. However, if we assume maximally a 1%
      risk in the spinal cord and a total NTCP for the two lungs of 100%, the mean TCP
      value for the five patients is increased from 6 to 49% with the best proton plan
      compared with x-rays only. The corresponding figure for the mixed plan is 27%.
      These gains are relatively insensitive to variations within reasonable limits in
      the biological parameters. CONCLUSIONS: Protons appear to have clear therapeutic
      advantages over conventional external radiotherapy when treating esophageal
      carcinoma.

PMID- 9607364
TI  - A test of the claim that plan rankings are determined by relative complication
      and tumor-control probabilities.
AB  - PURPOSE: This study tests an accepted claim regarding tumor control (TCP) and
      normal tissue complication (NTCP) probability functions. The claim is that
      treatment plans can be ranked using relative probabilities, even when the
      absolute probabilities are unknown. The assumption supports the use of
      probability models for plan optimization and the comparison of treatment
      techniques. METHODS: The claim was tested using a hypothetical model consisting
      of two tissues, and illustrated with clinical data. Plans were scored using the
      probability of uncomplicated tumor control. The scores of different plans were
      compared by fixing their relative risks for an individual tissue complication,
      but adjusting the absolute probability levels up or down. The tested claim is
      that the plan rankings should not change. RESULTS: In the two-tissue model, the
      rankings of competing plans were reversed by doubling all the probabilities. The
      preference ordering of lung cancer plans changed after the risk of pulmonary
      complication was reduced by 3-fold. In another site, the ranking of plans by
      overall complication-free probability was disturbed by errors that preserved the
      ordering of plans with respect to any individual complication. An adjustment of
      +/- 2.5% in the initial NTCP values for two tissues changed the direction in
      which a plan score moved in response to a fixed tradeoff in complication risk in
      an optimization search. CONCLUSIONS: Contrary to claims, plan rankings are not
      determined by the relative probabilities of adverse events. The effect on plan
      scores of trading one complication for another depends on the absolute levels of
      risk. Absolute errors in NTCP and TCP functions result in the wrong ranking of
      plans, even when relative probabilities are correct. An optimization routine
      based on TCP and NTCP calculations may be forced in the wrong direction by small
      errors in the probability estimates.

PMID- 9607365
TI  - The use of a standardized positioning support cushion during daily routine of
      breast irradiation.
AB  - PURPOSE: The use of positioning and immobilization techniques during external
      beam irradiation of the female breast is time consuming and expensive. The
      currently available standardized positioning devices are insufficient. For this
      reason, we designed a new and generally useable hard foam positioning support
      cushion for the use during breast irradiation, and tested its clinical usefulness
      in a prospective study. METHODS AND MATERIALS: Fifty-five female breast cancer
      patients receiving adjuvant radiotherapy following breast-conservative surgery
      were irradiated either without immobilization (n = 27) or with the positioning
      support cushion (n = 28). The time necessary for patient setup, the lying
      subjective comfort and--comparing portal images with simulator images--the
      reproducibility of the set up were determined. RESULTS: Irradiation
      reproducibility was significantly improved (average deviation without positioning
      support cushion: 8.4 mm, with positioning support cushion: 6.1 mm, p < 0.001).
      The time required for the positioning of the patient with positioning support
      cushion was in average 73 s, without cushion it was 55 s. A significantly higher
      proportion of patients (72%) found the position with the positioning support
      cushion as pleasant, whereas only 46% of patients were pleased with the position
      without cushion. CONCLUSION: The positioning support cushion designed in our
      department makes a substantial contribution to quality assurance in breast
      irradiation. It significantly increases the patients' comfort in a supine
      position. In contrast to conventional positioning and fixation aids it may be
      quickly and easily applied at low costs. Therefore, its use can be recommended.

PMID- 9607366
TI  - New method to obtain the midplane dose using portal in vivo dosimetry.
AB  - PURPOSE: The aim of this study was to develop a method to derive the midplane
      dose [i.e., the two-dimensional (2D) dose distribution in the middle of a patient
      irradiated with high-energy photon beams] from transmission dose data measured
      with an electronic portal imaging device (EPID). A prerequisite for this method
      was that it could be used without additional patient information (i.e.,
      independent of a treatment-planning system). Second, we compared the new method
      with several existing (conventional) methods that derive the midline dose from
      entrance and exit dose measurements. METHODS AND MATERIALS: The proposed method
      first calculates the 2D contribution of the primary and scattered dose component
      at the exit side of the patient or phantom from the measured transmission dose.
      Then, a correction is applied for the difference in contribution for both dose
      components between exit side and midplane, yielding the midplane dose. To test
      the method, we performed EPID transmission dose measurements and entrance,
      midplane, and exit dose measurements using an ionization chamber in homogeneous
      and symmetrical inhomogeneous phantoms. The various methods to derive the
      midplane dose were also tested for asymmetrical inhomogeneous phantoms applying
      two opposing fields. A number of combinations of inhomogeneities (air, cork, and
      aluminum), phantom thicknesses, field sizes, and a few irregularly shaped fields
      were investigated, while each experiment was performed in 4-, 8-, and 18-MV open
      and wedged beams. RESULTS: Our new method can be used to assess the midplane dose
      for most clinical situations within 2% relative to ionization chamber
      measurements. Similar results were found with other methods. In the presence of
      large asymmetrical inhomogeneities (e.g., lungs), discrepancies of about 8% have
      been found (for small field sizes) using our transmission dose method, owing to
      the absence of lateral electron equilibrium. Applying the other methods,
      differences between predicted and measured midplane doses were even larger, up to
      10%. For large field sizes, the agreement between measured and predicted midplane
      dose was within 3% using our transmission dose method. CONCLUSIONS: Using our new
      method, midplane doses were estimated with a similar or higher accuracy compared
      with existing conventional methods for in vivo dosimetry. The advantage of our
      new method is that the midplane dose can be determined in the entire (2D) field.
      With our method, portal in vivo dosimetry is an accurate alternative for
      conventional in vivo dosimetry.

PMID- 9607367
TI  - Repositioning accuracy: comparison of a noninvasive head holder with
      thermoplastic mask for fractionated radiotherapy and a case report.
AB  - PURPOSE: To compare accuracy, clinical feasibility, and subjective patient
      impression between a noninvasive head holder (Vogele Bale Hohner [VBH];
      Wellhoefer Dosimetry, Schwarzenbruck, Germany) developed at the University of
      Innsbruck and the thermoplastic mask fixation system for use in fractionated
      external radiotherapy. We present a case report of an actual patient fixated in
      the VBH head holder during radiation therapy. MATERIALS AND METHODS: The VBH head
      holder consists of an individualized vacuum dental cast connected to a head plate
      via two hydraulic arms allowing noninvasive, reproducible head fixation of even
      uncooperative patients. Accuracy was tested and compared with that of the
      thermoplastic mask using the Phillips EasyGuide navigation system on five
      volunteers. Specific external registration points served as landmarks and their
      positions were compared after each repositioning. System and operator inaccuracy
      were also taken into account. The times taken for production and repositioning of
      the respective fixation devices were compared, and subjective impressions were
      noted. RESULTS: Mean VBH head holder repositioning accuracy was 1.02 mm while
      that of the thermoplastic mask was 3.05 mm. 69% of mask repositionings showed a
      deviation > 2 mm and 41% > 3 mm (as opposed to 8% and 1% respectively for the VBH
      head holder) Those points located farthest away from the respective plane of
      fixation showed the largest deviations. Both production and repositioning times
      were similar between the systems; depending upon the patient, the VBH head holder
      was generally better tolerated than the mask system. CONCLUSION: Due to its
      significantly better repositioning accuracy compared to that of the thermoplastic
      mask, the VBH head holder is especially suited for external radiation requiring
      precise repositioning due to critical tissues in immediate surrounding of the
      area to be irradiated.

PMID- 9607368
TI  - The development and production of radiotherapy patient education videos using
      computer-based digital imagery.

PMID- 9607369
TI  - Advances in drug therapy for hypertension. Introduction.

PMID- 9607370
TI  - Clinical experience with endothelin antagonists.
AB  - Endothelin-1, discovered in 1988, is a 21-amino-acid peptide and currently the
      most potent vasoconstrictor and pressor substance known. Generated by vascular
      endothelial cells in response to a variety of chemical and mechanical signals,
      endothelin-1 is known to potentiate the actions of other vasoconstrictor
      substances and act as a comitogen in addition to directly causing
      vasoconstriction. There is evidence that endothelin-1 may contribute to the
      pathophysiology of conditions associated with sustained vasoconstriction, such as
      hypertension and heart failure, vasospastic conditions, such as subarachnoid
      hemorrhage, and atherogenesis. Studies using endothelin receptor antagonists show
      that endothelin-1 plays an important role in the maintenance of vascular tone and
      blood pressure in healthy humans, predominantly via an effect on the vascular
      smooth muscle ETA receptors. The endothelin receptor antagonist bosentan also
      effectively lowers blood pressure in hypertensive subjects and produces sustained
      and favorable effects on systemic and pulmonary hemodynamics in patients with
      chronic heart failure. A good side-effect profile, together with a potential for
      inhibition of atherogenesis, makes the endothelin receptor antagonists a
      potentially interesting class of novel agents for the treatment of cardiovascular
      disease.

PMID- 9607371
TI  - The physiological and pharmacological significance of cardiovascular T-type,
      voltage-gated calcium channels.
AB  - An influx of calcium ions into cells, made possible by the opening of specific,
      voltage-gated channels, triggers muscular contraction and several other
      physiological processes. Two types of calcium channels, L-type and T-type, are
      found in the cardiovascular system. These two types of channels differ
      considerably in their electrical and chemical characteristics and in their
      distribution in tissue. The L-type calcium channel is responsible for normal
      myocardial contractility and for vascular smooth muscle contractility. In
      contrast, T-type calcium channels are not normally present in the adult
      myocardium, but are prominent in conducting and pacemaking cells. They are
      thought to help regulate vascular tone, signal conduction, cardiac pacemaking,
      and the secretion of certain intercellular transmitters. T-Type channels also
      seem to have an important role in normal growth processes and in the tissue
      remodeling that occurs in pathologic processes such as cardiac hypertrophy.
      Traditional calcium antagonists act on L-type channels. Mibefradil is a recently
      characterized calcium antagonist and the first that is selective for T-type
      calcium channels. This unique property may lead to major applications in
      cardiovascular medicine.

PMID- 9607372
TI  - Mibefradil, a T-channel-selective calcium antagonist: clinical trials in
      hypertension.
AB  - Mibefradil, a tetralol derivative, is the first representative of a new class of
      calcium antagonists. It selectively blocks entry of calcium into cells through T
      type channels. The efficacy and tolerability of mibefradil in the treatment of
      mild-to-moderate essential hypertension were evaluated in four placebo
      controlled, double-blind, dose-finding studies involving over 1000 patients. Two
      trials involved patients from the general population, one examined a
      subpopulation of elderly patients, and one evaluated patients receiving chronic
      hydrochlorothiazide (HCTZ) treatment. Based on these studies, the recommended
      doses of mibefradil are 50 mg and 100 mg. Doses >100 mg/day were associated with
      small gains in efficacy and an increased incidence of adverse effects. Response
      (sitting diastolic blood pressure normalization to < or =90 mm Hg or reduction by
      > or =10 mm Hg) rates to mibefradil ranged from 46.0% to 68.6% with 50 mg, and
      from 60.0% to 93.2% with 100 mg. Normalization rates paralleled the response
      rates, ranging from 34.0% to 62.9% with 50 mg, and from 42.5% to 81.8% with 100
      mg. The effects on sitting systolic blood pressure were similar. Treatment was
      associated with a slight, potentially beneficial reduction in heart rate. Results
      were similar across all populations, indicating that no dose adjustment is
      required for elderly and for HCTZ-treated patients. The frequency of adverse
      events was similar to that reported for placebo groups, with headache being the
      most common complaint. In comparative trials, mibefradil was more effective than
      nifedipine SR and diltiazem CD, and at least as effective as amlodipine and
      nifedipine GITS. Overall, mibefradil was better tolerated than the comparison
      drugs. Mibefradil, at the recommended doses of 50 to 100 mg/day, is safe and
      effective for the treatment of mild-to-moderate hypertension.

PMID- 9607373
TI  - Mibefradil, a T-type channel-selective calcium antagonist: clinical trials in
      chronic stable angina pectoris.
AB  - Pharmacotherapy with nitrates, beta-blockers, and calcium antagonists is the
      cornerstone of management of patients with chronic stable angina pectoris. While
      these agents are all effective, their use may be limited by pharmacologic
      tolerance, side effects, and drug interactions. Mibefradil is a recently
      developed calcium antagonist with a unique chemical structure, pharmacologic
      profile, and mode of action. Unlike all previously available calcium antagonists,
      mibefradil acts primarily by selective blockade of T-type calcium channels,
      rather than L-type channels, at clinically relevant concentrations. It has been
      evaluated as a treatment for angina in placebo-controlled and active-controlled
      clinical trials. Treatment with 50 mg mibefradil resulted in a significant
      improvement in exercise tolerance test duration in three of the five placebo
      controlled trials, and a significant improvement in time to onset of angina in
      two of the five trials. Time to onset of ischemia as evaluated by 0.1 mV ST
      segment depression was increased in all five placebo-controlled trials. Treatment
      with 100 mg mibefradil resulted in significant improvement in all three exercise
      tolerance test parameters in all studies. Mibefradil further improved exercise
      tolerance test duration and other efficacy parameters when administered
      concomitantly to patients on background beta-blocker or nitrate therapy. In
      addition, treatment with mibefradil was associated with a dose-dependent decrease
      in heart rate, double product, frequency of anginal attacks, nitroglycerin
      consumption, and both frequency and duration of silent ischemic episodes. In
      comparative trials, 100 mg mibefradil once daily was superior in efficacy to 10
      mg amlodipine once daily and was at least equivalent to diltiazem in both
      efficacy and tolerability. Mibefradil was safe and well tolerated in all studies.

PMID- 9607374
TI  - Endothelin inhibition as a biologic target for treating hypertension.
AB  - Endothelin, a 21-amino-acid peptide, binds to a specific receptor on vascular
      smooth muscle cells, thereby inducing vasoconstriction. Although plasma levels
      are not consistently elevated in hypertension, there is evidence that endothelin
      has an important role in its pathogenesis. Administration of endothelin
      antagonists has lowered blood pressure and reduced end-organ damage in some
      animal models. It has also reduced the cross-sectional area of neointima due both
      to hypertension and vascular injury. Coadministration of endothelin and
      angiotensin II to rats produced a synergistic hypertensive effect. Similarly,
      coadministration of an endothelin antagonist with an angiotensin converting
      enzyme inhibitor resulted in a synergistic lowering of blood pressure. Several
      preliminary clinical studies have been done. The endothelin antagonist bosentan
      has decreased vascular resistance and blood pressure and increased cardiac index
      in patients with congestive heart failure. Plasma endothelin levels are elevated
      in the acute phase of myocardial infarction and in chronic heart failure. The
      magnitude of this increase, measured 3 days after patients experienced myocardial
      infarction, had a significance at least equal to known risk factors in predicting
      1 year survival. Thus, there are reasons to believe that endothelin antagonists
      may become a useful tool in the management of various cardiovascular disorders.

PMID- 9607375
TI  - Differential effects of angiotensin converting enzyme inhibition and diuretic
      therapy on reductions in ambulatory blood pressure, left ventricular mass, and
      vascular hypertrophy.
AB  - Diuretic-based therapy is less effective in reducing the cardiac complications of
      hypertension than the risk of stroke and may be less effective in reducing left
      ventricular (LV) mass than is therapy with angiotensin converting enzyme (ACE)
      inhibition. In view of the strong association of LV hypertrophy with
      cardiovascular risk, this study was designed to compare the impact of therapy
      with a diuretic and ACE inhibition on cardiac and vascular structure. Fifty
      essential hypertensives (74% male, 88% nonwhite) participated in a double-blind
      study for 6 months and were randomized to either ramipril or hydrochlorothiazide
      (HCTZ). Echocardiography, carotid ultrasonography, and ambulatory blood pressure
      (BP) monitoring were performed at baseline and 3 and 6 months after initiation of
      therapy. The 22 ramipril patients were comparable to the 28 HCTZ patients at
      baseline in age, race, and 24-h BP. Although HCTZ resulted in a greater reduction
      in 24-h BP, only treatment with ramipril resulted in a decrease in LV mass (193
      to 179 g, P < .005, v 184 to 182 g, P = NS), attributable to a reduction in wall
      thicknesses but not in chamber diameter. In multivariate analysis, both change in
      BP and treatment group were independent predictors of change in LV mass.
      Importantly, although neither drug reduced carotid artery cross-sectional area,
      relative wall thickness increased due to a tendency for vessel diameter to
      decrease and wall thickness to increase, particularly in the diuretic group.
      Ramipril caused a sustained fall in plasma angiotensin II, whereas HCTZ increased
      angiotensin II levels. Although diuretic therapy was more effective in lowering
      ambulatory BP in this predominantly nonwhite population, only therapy with ACE
      inhibition was associated with regression of LV mass. Vascular geometry was
      altered consistent with the reduction in distending pressure resulting in
      vascular remodelling.

PMID- 9607376
TI  - Salt sensitivity is associated with insulin resistance in essential hypertension.
AB  - The relationship between salt sensitivity and insulin resistance was investigated
      in nondiabetic, nonobese (body mass index < or = 28) untreated patients with
      uncomplicated, mild-to-moderate essential hypertension. Alterations in insulin
      mediated glucose disposal were assessed by means of the insulin suppression test.
      Subjects were classified as salt sensitive and salt resistant according to their
      blood pressure response to low and high salt intake. Fasting serum glucose levels
      were within normal limits and did not differ between salt sensitive and salt
      resistant hypertensives, irrespectively of the level of salt intake. Fasting
      serum insulin levels increased in salt sensitive patients when on a high intake
      of salt. The insulin suppression test revealed the existence of marked
      differences in insulin-mediated glucose uptake between salt sensitive and salt
      resistant hypertensives. Much higher steady-state glucose values (nanomoles of
      glucose/ liter) were obtained during the insulin suppression test in salt
      sensitive than in salt-resistant hypertensives (7.4+/-1.6 v 3.5+/-0.1 under low
      salt; and 12.5+/-1.1 v 4.3+/-0.1 under high salt intake). The product of glucose
      times insulin obtained at steady state during low and high salt intakes were 2.5
      and 5 times greater, respectively, in salt sensitive than in salt resistant
      hypertensives. Therefore, the impairment in insulin-mediated glucose disposal
      observed in salt sensitive hypertensives was present both under low salt (60 to
      70 mEq/day) and high salt intake (300 mEq/day). However, it was exacerbated under
      high salt intake. These results suggest that untreated salt sensitive
      hypertensives have a considerable impairment in insulin-mediated glucose disposal
      because of a state of insulin resistance. High salt intake increased BP, induced
      hyperinsulinemia, and worsened insulin-mediated glucose disposal only in salt
      sensitive patients. We propose that salt sensitivity contributes, separately from
      hypertension, to insulin resistance and thus be considered per se as an
      additional risk factor in the development of cardiovascular disease. Salt
      sensitivity and insulin resistance may be genetically associated conditions.

PMID- 9607377
TI  - Limited reproducibility of circadian variation in blood pressure dippers and
      nondippers.
AB  - The relation between blood pressure (BP) variation and hypertensive organ damage
      is controversial. The reproducibility of the circadian variation pattern
      acceptable as the standard for discriminating between "dippers" and "nondippers"
      has not yet been evaluated. We evaluated the reproducibility of "dipper" and
      "nondipper" patterns in essential hypertensives by monitoring BP for 48 h.
      Noninvasive ambulatory BP and heart rate (HR) monitoring for 48 h every 30 min
      were performed in 253 untreated patients with mild-to-moderate essential
      hypertension. Mean daytime (awake) and nighttime (sleeping) systolic BP,
      diastolic BP, and HR values were analyzed by reviewing the patients' diaries.
      Patients were divided into two groups by presence (dippers) and absence
      (nondippers) of a reduction of both systolic and diastolic BP during the night of
      > 10% of the daytime pressure. A subject who was a dipper on day 1 remained a
      dipper on day 2 in 41% (n = 103, DD group) and changed to nondipper in 16% (n =
      41, DN group). A subject who was a nondipper on day 1 remained a nondipper on day
      2 in 30% (n = 75, NN group) and changed to a dipper in 13% (n = 34, ND group).
      Our findings indicate that there is a high risk of false-positive or false
      negative results when 24-h recordings are used to identify dipper and nondipper
      profiles.

PMID- 9607378
TI  - Influence of diurnal blood pressure variations on target organ abnormalities in
      adolescents with mild essential hypertension.
AB  - As hypertensive target-organ damage has been associated with diminished diurnal
      blood pressure (BP) variation in adults, we compared diurnal BP patterns of
      hypertensive adolescents with left ventricular hypertrophy with normotensive and
      hypertensive adolescents with normal left ventricular mass. In addition, the
      frequency of microalbuminuria (Malb), hyperfiltration, and reduced renal
      functional reserve (RFR) was evaluated in adolescents with normal BP and
      untreated borderline and mild essential hypertension. Thirty-three normotensive
      (NT) adolescents, 14.5+/-2.1 years (mean +/- SD), and 29 untreated borderline and
      mildly hypertensive (HT) adolescents, 14.6+/-2.4 years, wore the SpaceLabs 90207
      ambulatory BP monitor for 24 h. Left ventricular mass was measured by M-mode
      echocardiography and then indexed (LVMI) to the cube of height. Creatinine
      clearance (Clcr) and urine Malb was measured on 24 h collection and RFR by change
      in creatinine clearance after an oral protein load. Diurnal BP change was
      expressed as the absolute and percent day-night BP fall and cusum derived plot
      height (CPH) and circadian alteration magnitude (CDCAM). Groups were compared
      using analysis of covariance with adjustments for race, gender, and body mass
      index. All NT and 19 HT subjects (HT-1) had normal LVMI at 22.2+/-5.3 and 25.8+/
      3.8 g/m3, respectively. Ten HT (HT-2) had increased LVMI of 36.9+/-5.2 g/m3. No
      significant difference was found for absolute or percent day-night BP fall or
      CDCAM between groups. Nocturnal systolic BP was correlated most closely with LVMI
      (r = 0.41, p = .001). Clcr, Malb, and RFR did not differ between the groups. In
      conclusion, adolescents with borderline and mild essential hypertension and left
      ventricular hypertrophy have similar levels of diurnal BP fall, urine Malb
      excretion, and RFR compared to normotensive and hypertensive adolescents with
      normal left ventricular mass.

PMID- 9607379
TI  - The impact of obesity and body fat distribution on ambulatory blood pressure in
      children and adolescents.
AB  - To assess the relationship between obesity, body fat distribution, and blood
      pressure in children and adolescents, various measures of obesity and the waist
      to-hip circumference ratio were related to casual and ambulatory blood pressure
      as measured using a SpaceLabs 90207 monitor during a regular school day. Seventy
      obese and 70 nonobese children aged 6 to 16 years were included in the study.
      Regardless of the time period analyzed (24 h, daytime, or nighttime), ambulatory
      blood pressure and casual blood pressure were significantly higher among the
      obese children. The differences in systolic blood pressure observed between the
      groups were attributable to the presence of obesity as estimated by the ponderal
      index and by skinfold thickness. Similarly, systolic and diastolic loads, as an
      assessment of high blood pressure values over 24 h, were significantly higher in
      the obese children when compared to the loads for the nonobese children. Waist-to
      hip circumference ratio was independently associated, (in multiple regression
      analysis) with systolic blood pressure, whether during 24 h, daytime, or
      nighttime periods, after controlling for age, sex, current height, ponderal
      index, and tricipital skinfold thickness. This study demonstrates that obesity is
      a determinant of ambulatory and casual blood pressure. Since obese children with
      a predominantly abdominal fat mass show higher blood pressure values, evaluation
      of body fat distribution in children may help to identify subjects more
      susceptible to developing hypertension later in life.

PMID- 9607380
TI  - Aging and essential hypertension: effect of left ventricular hypertrophy on
      cardiac function.
AB  - This study was designed to analyze the cardiac effects of aging and of
      hypertension in patients with essential hypertension and with or without left
      ventricular hypertrophy (LVH). Thirty-one patients <55 years old and 66 patients
      >64 years old with essential hypertension were divided according to the presence
      or absence of LVH. Cardiac functional structure was assessed by 2D-guided M-mode
      echocardiography. The peak filling rate and the duration of rapid filling were
      obtained by digitizing septal and posterior wall echoes. In the older group only
      was systolic function significantly impaired in subjects with LVH when compared
      with subjects without LVH [velocity of circumferential fiber shortening (L/msec):
      1.40+/-0.24 v 1.18+/-0.25; fractional fiber shortening (%): 43.06+/-5.02 v
      36.26+/-7.1; ejection fraction (%): 81.1+/-5.1 v 73.13+/-9.2; P < .05]. Older
      patients, even without LVH, showed a longer duration of rapid filling (321.0+/
      108.3 msec) and lower peak filling rate (7.01+/-1.86 cm/sec) in comparison with
      younger persons with or without LVH. In the older subjects the increase in left
      ventricular mass was associated with a decrease of velocity of circumferential
      fiber shortening (r = -0.48, P < .01), fractional fiber shortening (r = -0.40, P
      < .01), and ejection fraction = -0.50, P < .01), whereas there was no correlation
      in the younger group. The present findings of impaired diastolic filling even in
      the absence of LVH in the elderly, and the deterioration of systolic function
      parallel to the increase in LV mass suggest that aging is associated with a
      decrease in the number of functioning contractile elements per unit of cardiac
      mass.

PMID- 9607381
TI  - Microalbuminuria is an early marker of target organ damage in essential
      hypertension.
AB  - Microalbuminuria has been associated with a cluster of metabolic and nonmetabolic
      risk factors, suggesting that it might indicate the presence of generalized
      microvascular damage in patients with essential hypertension. To explore whether
      microalbuminuria is associated with early target organ damage, two groups of
      essential hypertensive patients, with (n = 17) (HtAlb+) and without (n = 16)
      (HtAlb-) microalbuminuria, and a control group (C) of healthy normotensive
      subjects (n = 20) were studied. The study groups, selected among participants of
      a large epidemiologic trial, were carefully matched for several potentially
      confounding variables such as gender, age, duration of hypertension, and body
      mass index. Albumin excretion rate was evaluated by radioimmunoassay in three
      nonconsecutive timed overnight collections after 3 weeks of pharmacologic wash
      out. Left ventricular mass was assessed by M-B-mode echocardiography, carotid
      wall thickness by a high resolution ultrasound scan, and renal vascular impedance
      by Doppler scan. Office as well as 24-h ambulatory pressure monitoring (Takeda TM
      2420) were also evaluated. There was no difference between the two hypertensive
      groups for office and 24-h blood pressure levels except for a lower
      daytime/nighttime systolic blood pressure ratio in the group with
      microalbuminuria. Microalbuminuric patients showed signs of early organ damage as
      compared to normoalbuminuric patients and normal subjects, namely greater left
      ventricular mass indices (LVMI 167+/-7 g/m2 in HtAlb+; 139+/-9 g/m2 in HtAlb-;
      118+/-5 g/m2 in C, P < .001) and increased wall thickness of common carotid
      arteries (intima plus media thickness 12.5+/-0.2 mm in HtAlb+; 11.7+/-0.3 mm in
      HtAlb-; 11.2+/-0.2 mm in C, P < .001) as well as higher intrarenal vascular
      resistance (mean resistive index 0.62+/-0.01 in HtAlb+; 0.59+/-0.01 in HtAlb-;
      0.59+/-0.01 in C, P < .05). In conclusion, microalbuminuria is an early marker of
      diffuse target organ damage in essential hypertension and therefore can be useful
      to identify patients for whom more aggressive preventive strategies or additional
      treatment measures are advisable.

PMID- 9607382
TI  - Angiotensinogen gene M235T and T174M polymorphisms in essential hypertension:
      relation with target organ damage.
AB  - The molecular variants M235T and T174M of the angiotensinogen gene have been
      linked to essential hypertension in some populations, but there are discrepancies
      about this association in other studies. We studied 75 patients with essential
      hypertension (BP > 160/100 mm Hg) from our outpatient clinic, aged 55+/-1 years,
      30 men, systolic BP 182+/-2.5, diastolic BP 109+/-1 mm Hg (mean +/- SEM), and a
      family history of the disease. Target organ damage was evaluated by measuring
      urinary albumin excretion rate, left ventricular hypertrophy, and fundoscopy. As
      a control group, 75 healthy subjects with BP < 130/85 mm Hg and with no family
      history of cardiovascular disease were selected. M235T and T174M angiotensinogen
      genotypes were determined by PCR and subsequent digestion of the products with
      SfaNI and NcoI, respectively. The frequency (q) of genotypes of the variant M235T
      in the patients with essential hypertension was MM 0.31, MT 0.41, and TT 0.28,
      not significantly different (P = .93) from that of the controls (MM 0.28, MT
      0.44, and TT 0.28). For the variant T174M, the genotype frequencies in
      hypertensives were TT 0.83, TM 0.15, and MM 0.02, which was not significantly
      different (P = .89) from that of the controls (TT 0.86, TM 0.12, and MM 0.02).
      Similarly, there was no evidence for association between angiotensinogen
      genotypes and hypertension in subjects aged < or = 40 years old (n = 24) or with
      severe (stage III) hypertension (n = 31). Within the group of patients with
      essential hypertension, there were no differences in genotype distribution
      between patients with and without retinopathy (n = 31), left ventricular
      hypertrophy (n = 37), or microalbuminuria (n = 14). This study shows that M235T
      and T174M variants are not associated either with essential hypertension or with
      target organ damage in a Spanish sample.

PMID- 9607383
TI  - Comparative efficacy of two angiotensin II receptor antagonists, irbesartan and
      losartan in mild-to-moderate hypertension. Irbesartan/Losartan Study
      Investigators.
AB  - The primary objectives of this double-blind study were to compare the
      antihypertensive efficacy and tolerability of irbesartan and losartan, two
      angiotensin II (AT1 subtype) receptor antagonists with different pharmacokinetic
      profiles in patients with mild-to-moderate hypertension. Both drugs are approved
      for once-daily use (although losartan may also be prescribed twice-daily). After
      a placebo lead-in, 567 patients were randomized (1:1:1:1) to once-daily therapy
      with placebo, 100 mg losartan, 150 mg irbesartan, or 300 mg irbesartan for 8
      weeks. Treatment groups had comparable demographic and baseline characteristics.
      After 8 weeks of treatment, reductions from baseline in trough seated diastolic
      blood pressure (SeDBP) and trough seated systolic blood pressure (SeSBP) with 300
      mg irbesartan were greater than with 100 mg losartan (P < .01 for both
      comparisons), by 3.0 and 5.1 mm Hg, respectively; larger reductions were also
      demonstrated at weeks 1 and 4 (P < .01 and P = .017, respectively, for SeDBP).
      Throughout the study, the antihypertensive effect of 150 mg irbesartan did not
      differ significantly from that of 100 mg losartan. All therapies were well
      tolerated. The 300 mg dose of irbesartan was associated with the lowest incidence
      of adverse events (AE) and discontinuations because of AE. This study
      demonstrates that the maximally effective once-daily doses of two different AT1
      receptor antagonists may result in clinically significant differences in blood
      pressure reductions, and therefore highlights the potential importance of the
      pharmacokinetic and pharmacodynamic differences between these two members of this
      class.

PMID- 9607384
TI  - A randomized, double-blind, placebo-controlled, parallel-group, multicenter trial
      of four doses of tasosartan in patients with essential hypertension. Tasosartan
      Investigator's Group.
AB  - Tasosartan, a new, long-acting, nonpeptide angiotensin II receptor antagonist was
      evaluated in a randomized, double-blind, placebo-controlled, multicenter trial at
      21 sites in the United States and Canada. After a 2-week, placebo washout
      qualification period, 278 patients (187 men/91 women) with a mean age of 53.4+/
      9.5 years (range, 30 to 70 years) and a baseline sitting diastolic blood pressure
      (DBP) of 95 to 114 mm Hg were randomly assigned to receive placebo (n = 56), or
      10 mg (n = 57), 30 mg (n = 55), 100 mg (n = 55), or 300 mg (n = 55) tasosartan
      for 4 weeks. The treatment period was followed by a 2-week washout period.
      Ambulatory blood pressure (BP) monitoring was performed at the end of the placebo
      washout period and after at least 4 weeks of double-blind treatment. Clinically
      significant placebo-adjusted differences in baseline sitting systolic blood
      pressure (SBP)/DBP were observed in the 10 mg (5/3 mm Hg), 30 mg (5/4 mm Hg), 100
      mg (10/7 mm Hg) and 300 mg (10/7 mm Hg) dose groups (P < .05). A dose-response
      relationship (P < .001) was observed within 1 to 2 weeks of treatment initiation
      and was maintained throughout the double-blind period. Discontinuation of
      tasosartan therapy was not associated with rebound hypertension. Moreover,
      significant (P < .05) placebo-adjusted differences in ambulatory SBP/DBP and a
      significant dose-response relationship (P < .001) were observed with all
      tasosartan dosages during the 24-h, daytime, and nighttime periods. Placebo
      adjusted trough-to-peak ratios ranged from 87% to 100% for ambulatory SBP and 64%
      to 81% for DBP. In general, no significant differences were observed between the
      tasosartan treatment groups and the placebo group in the incidence of adverse
      events. Headache incidence was significantly lower in the 300 mg dose group than
      the placebo group. In conclusion, tasosartan at dosages of 10, 30, 100, or 300 mg
      given once daily produced a significant and dose-related reduction in both clinic
      and ambulatory BP that was maintained over the 24-h period. Tasosartan was
      generally well tolerated.

PMID- 9607385
TI  - Dose-related antihypertensive effects of irbesartan in patients with mild-to
      moderate hypertension.
AB  - Two multicenter, double-blind, placebo-controlled, parallel group studies were
      conducted to evaluate the efficacy, safety, pharmacokinetics, and
      pharmacodynamics of the angiotensin II receptor (AT1 subtype) antagonist
      irbesartan. The effect of irbesartan withdrawal and the effect of adding
      hydrochlorothiazide (HCTZ) to irbesartan were also assessed. After a placebo lead
      in phase, all patients were randomized to 8 weeks of double-blind therapy with
      either placebo (n = 158) or irbesartan at doses of 1, 5, 10, 25, 50, 100, 200, or
      300 mg (n = 731 total) orally once daily. Irbesartan reduced blood pressure in a
      dose-related manner. Reductions from baseline in trough seated diastolic blood
      pressure ranged from 7.5 mm Hg for 50 mg irbesartan to 11.6 mm Hg for 300 mg
      irbesartan. At week 8, statistically significant reductions over placebo were
      observed in trough seated blood pressure with all irbesartan doses > or = 50 mg.
      These reductions reached statistical significance versus placebo within 2 weeks
      with 100, 200, and 300 mg irbesartan. Plasma irbesartan concentrations correlated
      with dose. Angiotensin II and aldosterone levels generally showed dose-related
      changes, consistent with AT1 receptor blockade. In patients not controlled at 8
      weeks, the addition of 12.5 mg HCTZ resulted in further dose-related reductions
      in blood pressure. Irbesartan demonstrated a placebo-like safety profile and no
      dose-related toxicity. Irbesartan, administered alone or in combination with
      HCTZ, was well tolerated. Withdrawal of irbesartan did not result in rebound
      hypertension or adverse events. Thus, once-daily irbesartan is both an effective
      and safe antihypertensive agent for the treatment of mild-to-moderate
      hypertension.

PMID- 9607386
TI  - Replacing short-acting nifedipine with alternative medications at a large health
      maintenance organization.
AB  - In response to recent evidence about the safety of calcium channel blockers,
      Group Health Cooperative of Puget Sound (GHC), a large health maintenance
      organization, implemented a plan in April 1996 to reevaluate the medications of
      1349 patients who were taking short-acting nifedipine. Following the
      intervention, 79.8% of patients taking short-acting nifedipine discontinued use,
      and 45.6% switched to once-daily felodipine. By presenting physicians and
      patients with recent evidence about the safety of short-acting nifedipine, a
      large health maintenance organization was able to motivate broad-scale changes to
      safer alternative drug therapies.

PMID- 9607387
TI  - Compliance and antihypertensive efficacy of amlodipine compared with nifedipine
      slow-release.
AB  - Poor compliance is a principal cause of treatment failure in hypertensive
      patients. Once-daily dosing improves compliance, but 24-h antihypertensive
      activity should be provided. The compliance, efficacy, and safety of amlodipine
      and nifedipine slow-release (SR) were compared in patients with mild-to-moderate
      essential hypertension recruited among 24 centers in France. After a 2-week
      washout period, 103 patients were randomized to 12 weeks of 5 to 10 amlodipine mg
      once daily (n = 55) or 20 mg nifedipine SR twice daily (n = 48). Compliance was
      calculated by electronic drug monitoring. Efficacy was measured by ambulatory and
      casual BP recordings. Patients receiving amlodipine demonstrated better
      compliance than patients receiving nifedipine SR with respect to compliance index
      (the total number of doses taken divided by the total number of doses prescribed,
      expressed as a percentage; 98.3% v 87%; P < .0001), days on which the correct
      number of doses were taken (92.5% v 74.8%; P < .0001), and prescribed doses taken
      on schedule (88.7% v 71.6%; P < .0001). Absolute and relative therapeutic
      coverage were higher in patients receiving amlodipine than nifedipine SR (P <
      .0001). Mean SBP and DBP decreased equally in both groups, although amlodipine
      offered better BP control compared with nifedipine SR at specific times of day.
      Fewer patients had high nocturnal SBP with amlodipine (39.3%) than nifedipine SR
      (71.4%; P = .042). Adverse events and treatment withdrawals occurred less
      frequently in amlodipine-treated patients than in nifedipine SR-treated patients.
      Amlodipine (5 to 10 mg) once daily provides improved compliance, better 24-h BP
      control, and fewer adverse events than 20 mg nifedipine SR twice daily in
      patients with mild-to-moderate hypertension.

PMID- 9607388
TI  - Changes in the costs of antihypertensive medications in a developing country: a
      study in Mexico comparing 1990 and 1996.
AB  - In developing countries, the cost of antihypertensive medications is one of the
      principal limiting factors when trying to treat patients with high blood
      pressure. To determine the changes in cost (in US dollars) of these medications
      and in the percentage of the minimum wage needed to purchase them, two cost
      studies (1990 and 1996) done in Mexico were compared. The yearly cost of a
      treatment with hydrochlorothiazide was US $13.80 in 1990; in 1996 it was US
      $10.92. Both figures represent 1.1% of the minimum wage that was in effect at the
      time. Propranolol hydrochloride cost US $50.52 for a year's treatment in 1990,
      and US $66.12 for the same in 1996. These figures represented, respectively, 4.2%
      and 6.7% of the minimum wage of 1990 and 1996. The annual cost for nifedipine was
      US $176.76 in 1990 (14.7% of the minimum wage) and US $242.16 in 1996 (24.8% of
      the minimum wage). The yearly cost of enalapril was US $233.04 in 1990 and US
      $433.20 in 1996; these costs represented, respectively, 19.4% and 44.2% of the
      minimum wage. The comparison of these two cost studies (1990 and 1996) shows why
      Mexico's population is finding it more difficult to purchase antihypertensive
      medications. Higher costs and reduced purchasing power seem to be the two
      principal factors causing this. This is probably affecting the population's
      health, as it is more difficult to control high blood pressure without proper
      treatment.

PMID- 9607389
TI  - Insulin receptor number in arterial hypertension: response to treatment with
      fosinopril or atenolol.
AB  - Human insulin receptor (hINR) number and its response to medical treatment was
      evaluated in 14 male controls and 40 male hypertensive patients. Twenty patients
      treated with fosinopril (10 to 20 mg daily orally) comprised Group A and 20
      treated with atenolol (25 to 50 mg daily orally) Group B. The hINR number
      (receptors x 10(3)/red cell) was greater in controls compared to untreated
      patients (8.22+/-2.4 v 5.53+/-1.27, P < .001). After 6 months of treatment the
      hINR number increased in Group A (5.73+/-1.47 v 7.5+/-2.06, P < .001) and
      remained unchanged (5.35+/-1.09 v 5.5+/-1.31, P = NS) in Group B. Thus, hINR
      number is decreased in hypertension and, in contrast to atenolol, fosinopril
      treatment is associated with an increase in hINR number, suggesting a favorable
      effect on glucose metabolism.

PMID- 9607390
TI  - Hypertension in young patients after renal transplantation: ambulatory blood
      pressure monitoring versus casual blood pressure.
AB  - The results of ambulatory blood pressure monitoring (ABPM) in children after
      kidney transplant were analyzed to ascertain any alteration in circadian BP
      profile, degree of hypertension, and efficacy of therapy. The data were also
      compared with casual BP data and left ventricular mass index (LVMI). We have
      examined 30 patients (17 male, 13 female), mean age 16.1+/-3.6 years after kidney
      transplant. All patients were receiving triple immune-suppressive therapy and 20
      of them were also taking antihypertensive therapy. They underwent clinical
      examination with measurement of BP at rest, echocardiogram mono-2D, and ABPM. The
      following ABPM parameters were recorded: systolic (S) and diastolic (D) BP at
      rest; mean 24-h SBP and DBP; mean daytime SBP and DBP; mean nighttime SBP and
      DBP; nocturnal fall in SBP and DBP; and mean daytime and nighttime heart rate
      (HR). The patients were divided in two groups. Group A consisted of 20 patients
      taking antihypertensive treatment; group B consisted of 10 patients not taking
      antihypertensive treatment. Casual and ABPM data for the two groups were compared
      using the Student t test for unpaired data. Blood pressure at rest and LVMI were
      not statistically different between the two patient groups. The ABPM data showed
      statistical differences between the two groups for mean 24-h SBP and DBP, daytime
      and nighttime SBP, nighttime DBP, fall in nocturnal DBP, and nighttime HR. Mean
      24-h SBP and DBP, mean daytime SBP and DBP, and mean nighttime SBP and DBP were
      significantly correlated to LVMI (respectively, P = .009, P = .005, P = .008, P =
      .007, P = .05, and P = .01). Twenty-four-hour ABPM was more useful in the
      diagnosis and management of hypertension than was casual BP at rest.

PMID- 9607391
TI  - No association between alpha-adducin 460 polymorphism and essential hypertension
      in a Japanese population.
AB  - Many unknown genetic factors are involved in the pathogenesis of hypertension.
      Recently, the reverse genetic approach revealed that some genetic variants, such
      as angiotensinogen, lipoprotein lipase, and alpha-adducin gene polymorphisms,
      increase the risk for hypertension. Both in rat and human, the genetic
      predisposition to hypertension was confirmed only for angiotensinogen and alpha
      adducin genes. Adducin is a membrane cytoskeletal protein, which is thought to
      regulate sodium transport. Abnormalities of membrane sodium transport in the
      kidney play an important role in hypertension. A recent report by Cusi et al
      showed that the Trp allele of alpha-adducin polymorphism (Gly 460 Trp) is
      associated with an increased risk of hypertension in whites, which led us to
      carry out a case-control study to examine whether the same association is
      observed in the Japanese population. We recruited 170 hypertensive and 194
      normotensive Japanese subjects and compared the genotype distribution of alpha
      adducin 460 polymorphism between cases and controls and between whites and
      Japanese. Trp allele frequency of controls in the Japanese subjects was twice as
      high as in the whites. However, no association was observed between alpha-adducin
      polymorphism and hypertension. Furthermore, alpha-adducin 460 polymorphism was
      not associated with any clinical characteristics. Accordingly, we concluded that
      alpha-adducin 460 polymorphism is not a major genetic risk for hypertension in
      Japanese people.

PMID- 9607393
TI  - Thoracic myelopathy in the Japanese: epidemiological and clinical observations on
      the cases in Miyagi Prefecture.
AB  - Surgeries for thoracic myelopathy for 7 years in a northeastern prefecture
      (population, 2.26 million) and surrounding areas were reviewed. Eighty-one
      residents in the prefecture were operated on. The annual operation rate per one
      million people was 5.1. The rate corresponded to 9% of that reported for cervical
      myelopathy in the same prefecture. The mean age at operation was 55 years. Fifty
      five patients (68%) were male and 26 (32%), female. Twenty-eight % of the
      patients had preoperative periods longer than two years, and 23% had severe
      disabilities. Anterior decompression was performed in 27%, posterior
      decompression in the others. The postoperative recovery rate averaged 48%. The
      lowest rate was 31% in patients with a preoperative duration of more than 2 years
      (p < 0.05). Sixty-four % of the patients had ossification of the ligamentum
      flavum; 20%, posterior spur; 19%, disc herniation; 16%, ossification of the
      posterior longitudinal ligament; 1%, calcification of the ligamentum flavum; 1%,
      degenerative spondylolisthesis. Seventy-nine % had one of the above spinal
      factors and 21% had two.

PMID- 9607392
TI  - In vivo evaluation of in vitro hypothesis using "gain or loss" of function:
      functional analysis of renin-angiotensin system.
AB  - Characterization of the role of components of the renin angiotensin system (RAS)
      in vivo is limited by the difficulty in manipulating these individual components,
      as well as by methodologic limitations in studying the function of a local RAS in
      the absence of any contribution by the circulating RAS. In vivo gene transfer
      technology provides us with the opportunity to study the physiologic responses to
      in vivo manipulation of the individual components related to hypertension (ie, by
      overexpression or inhibition) without changes in the circulating system. Using
      this technology, the importance of each component of RAS in blood pressure
      regulation has recently been shown. Such an approach may increase our
      understanding of the biology and pathobiology of the autocrine-paracrine system
      in hypertension. This review discusses the potential utility of in vivo gene
      transfer methods.

PMID- 9607394
TI  - Peak systolic stress-rate-corrected mean velocity of fiber shortening in preterm
      and fullterm infants.
AB  - The relation of rate-corrected mean velocity of fiber shortening (mVcfc)-end
      systolic wall stress (ESS) is a load-independent index of left ventricular
      contractility, but involves simultaneous M-mode echocardiography, carotid or
      axillary pulse tracing and blood pressure determination, which may be impractical
      in younger infants. We examined whether the relation of the peak systolic wall
      stress (PSS)-mVcfc could be used as a simpler method of assessing left
      ventricular contractility in preterm and fullterm infants. In 45 preterm and
      fullterm infants, mVcfc, ESS, and PSS were determined using echocardiography,
      axillary pulse tracing and blood pressure measurement. Five patients with left
      ventricular dysfunction or low cardiac output state were also studied. The
      relation of PSS and ESS was PSS=5.19+1.04 ESS (r=0.98, p<0.01). The slope of
      mVcfc=1.58-0.012 ESS (r=-0.78, p<0.01) was nearly identical to that of mVcfc=1.60
      0.011 PSS (r=-0.75, p<0.01), with no difference in the regression coefficients.
      The relationship of PSS and ESS in 5 patients was very close and the slope of the
      regression line was nearly identical to that of 45 infants. The relation of mVcfc
      PSS correlates well with the relation using ESS and can be used as a simple
      method of assessing left ventricular contractility.

PMID- 9607395
TI  - Significance of measurement of prostate specific antigen (PSA) in familial
      prostate cancer lines.
AB  - The concentration of prostate specific antigen (PSA) in serum was measured in 20
      brothers or sons in 10 families in which the father and son or brothers had
      prostate cancer using the E test TOSOH IIPA. The patients were between 32 and 70
      years old with a mean age of 48.2 years. The PSA value was between 0.4 and 19.5
      ng/ml with a mean value of 3.4 ng/ml. Five patients (25%) had PSA values
      exceeding the cut-off value of 4.0 ng/ml. After obtaining their consent,
      systematic prostate needle biopsy by transrectal ultrasonography was performed on
      3 patients (15%). Prostate cancer was detected in all of them. Among them 2
      patients were brothers, and since the other two brothers already had prostate
      cancer, all four brothers were confirmed to have prostate cancer. This is the
      first report of a familial prostate cancer in four brothers in Japan. In the
      western countries where the incidence of prostate cancer is higher than that in
      Japan, studies have been performed on the risk factors. Family history is one of
      the most important risk factors. In Japan, the incidence of prostate cancer is
      increasing rapidly. Moreover, patients with a prostate cancer family history are
      expected to increase. In such cases, prostate cancer screening should be
      performed aggressively from a young age.

PMID- 9607396
TI  - Practical assay method of cytosolic acetoacetyl-CoA thiolase by rapid release of
      cytosolic enzymes from cultured lymphocytes using digitonin.
AB  - We designed a simple approach to determine cytosolic acetoacetyl-CoA thiolase
      (CT) activity for differential diagnosis of ketone body catabolic defects, using
      rapid cell-subfractionation of cultured lymphocytes with digitonin. Efficiency of
      cell subfractionation was determined by measurement of lactate dehydrogenase and
      citrate synthetase as marker enzymes for cytosol and organelle fractions,
      respectively, and confirmed by immunotitration and immunoblotting using
      antibodies against cytosolic and mitochondrial thiolases, respectively. In the
      condition of best separation taken in the presence of 1 mg/ml digitonin,
      acetoacetyl-CoA thiolase activities in the presence of K+ ion in the cytosol and
      organelle fractions were 138.3+/-39.2 and 84.0+/-16.2 nmol/min/ml, respectively.
      The thiolase activity in the organelle fraction was doubled by the presence of K+
      ion, whereas that in the cytosol fraction was not affected. The thiolase activity
      in the organelle fraction was reduced by the treatment of anti-mitochondrial
      acetoacetyl-CoA thiolase (T2) antibody but not by anti-CT antibody. On the other
      hand, that in the cytosol fraction was significantly decreased by anti-CT
      antibody but not by anti-T2 antibody. These data suggested that T2 was collected
      in the organelle fraction, and that CT activity could be assessed by measurement
      of the thiolase activity in the cytosolic fraction. Succinyl-CoA: 3-ketoacid CoA
      transferase (SCOT), whose defect is the third inherited disorder of ketone body
      catabolism, was collected in the organelle fraction. Hence, this method will
      prove to be useful for accurate assessment of defects of CT as well as T2 or
      SCOT, all involved in ketone body catabolism.

PMID- 9607397
TI  - Preparation of liposome-encapsulating adenosine triphosphate.
AB  - Liposomes encapsulating adenosine triphosphate (ATP) were prepared by sonication,
      and the liposomes were evaluated for use in a drug delivery system. The
      liposomes, which were composed of phosphatidylcholine and cholesterol, were about
      1.1 microm in size, as observed under a microscope. From their size, the vesicles
      were thought to be multilamellar. The maximum concentration of ATP in the
      liposomes was 1.0 mM, when the initial concentrations of lipid and ATP were 20 mM
      and 300 mM, respectively. The maximum entrapment ratio of ATP in the liposomes
      was 88%, when the initial concentrations of lipid and ATP were 20 mM and 500 mM,
      respectively. About 4% of ATP was encapsulated in these experiments. When
      liposomes contained 4-7% of cholesterol, about 35% of encapsulated ATP was
      released from the liposomes for 90 hours at 37 degrees C in vitro. These findings
      indicated that liposomes encapsulating ATP could be used for the treatment of
      ischemic retina.

PMID- 9607398
TI  - Elevation of plasma peptide YY and pancreatic juice hypersecretion following
      massive small bowel resection in the rat.
AB  - To clarify a physiological role of endogenous peptide YY(PYY) on pancreatic
      exocrine secretion, gastrointestinal transit and bile flow, a hyper-PYY-emia
      model was constructed by performing a massive small bowel resection using rats.
      (1) 75% resection of the small intestine was performed at its distal side. Two
      weeks after surgery, these rats were fed a liquid meal, and intestinal transit of
      contents was observed and plasma PYY and secretin concentrations were measured by
      radioimmunoassay. (2) Two weeks after the same surgery, a liquid meal was infused
      into the duodenum, and both pancreatic juice and bile were collected separately
      under general anesthesia. Transit of the intestinal contents from the pyloric
      ring, plasma CCK concentrations, pancreatic juice flow, amylase output, and bile
      flow were determined. Hyper-PYY-emia occurred following surgery both at fasting
      and after feeding, accompanied by retardation of gastrointestinal transit,
      increase of pancreatic juice flow and decrease of bile flow. Plasma secretin
      levels were elevated slightly, while CCK levels remained unchanged. In
      conclusion, massive small bowel resection is a useful model to induce hyper-PYY
      emia in rats. It is considered that, in a malnutritional state after small
      intestinal resection, a colonic regulatory mechanism, via humoral factors such as
      PYY, participates in the feedback regulation of proximal intestinal as well as of
      pancreatic function.

PMID- 9607399
TI  - Progression of prostatic cancer in relation to age in patients detected by mass
      screening program.
AB  - With the aim of revealing the natural history of prostatic cancer, the
      distribution of age was examined in relation to disease progression in patients
      detected by mass screening programs. Between 1975 and 1996, such programs
      detected a total number of 132 patients with prostatic cancer. The mean ages of
      patients with Stage B, Stage C and Stage D disease were 71.2, 73.8 and 75.3
      years, respectively. This might suggest that the difference of 3 years in mean
      age between Stage B and Stage C disease reflects the time interval of the
      progression of prostatic cancer from the early (Stage B) to the advanced (Stage
      C) stage. These results coincided well with the natural history of prostatic
      cancer, which we proposed previously based upon the "size of ranking" analysis of
      latent prostatic cancer and doubling time obtained from ultrasonic measurement of
      prostatic volume. An epidemiological study of prostatic cancer detected by mass
      screening would offer data of value for the elucidation of the natural history of
      that disease.

PMID- 9607400
TI  - Myositis ossificans in the tip of the thumb: a case report.
AB  - A case of a myositis ossificans occurring in the distal portion of the finger is
      reported. An 18-year-old female noticed a small nodule in the tip of the left
      thumb for 11 months. Plain radiographs showed calcified shadow and there was a
      radiolucent zone between the mass and the distal phalanx. The excised mass was
      diagnosed as myositis ossificans. To our best knowledge, there has been no report
      of a myositis ossificans in the tip of the finger in literature.

PMID- 9607401
TI  - Physiological mechanisms in regulation of blood pressure fast frequency
      variations.
AB  - Spectral analysis of blood pressure fast oscillations (short-term variability),
      both in humans and animals, reveals three major frequential domains: the very low
      , low- and the high-frequency domain. In this paper, experimental data providing
      evidence for physiological mechanisms involved in the regulation of blood
      pressure oscillations such as sympathetic nervous system, renin-angiotensin
      system, NO, respiration, heart function, and circulating blood volume are
      reviewed. In addition, novel evidence is provided by the author for vasopressin
      modulation of the low- and high-frequency blood pressure components. This review
      suggests that the multiplicity of factors involved in the genesis of the blood
      pressure spectral components imply utmost caution in interpreting spectral
      results.

PMID- 9607402
TI  - Density and localization of calcium channels of the L-type in human pulmonary
      artery.
AB  - The pharmacological profile and the anatomical localization of Ca2+ channels of
      the L-type were investigated in the human pulmonary artery to identify possible
      mechanisms involved in the regulation of the pulmonary vascular tone. Analysis
      was performed on slide-mounted frozen sections of human pulmonary artery using
      radioligand binding assay techniques associated with light microscope
      autoradiography. [3H]-Nicardipine was used as ligand. Human renal and right
      coronary arteries also were used as systemic reference arteries. Binding of [3H]
      nicardipine to sections of human pulmonary artery was time-, temperature- and
      concentration-dependent, saturable and reversible. In the human pulmonary artery,
      the apparent equilibrium dissociation constant (Kd) was 0.12+/-0.02 nM and the
      maximum density of binding sites (Bmax) was 38.15+/-2.25 fmol/mg tissue. Kd
      values were 0.3+/-0.01 nM and 0.5+/-0.02 in the human renal artery and right
      coronary artery respectively. Bmax values were 248+/-16 fmol/mg tissue and 173+/
      9.5 fmol/mg tissue in the human renal artery and right coronary artery
      respectively. The pharmacological profile of [3H]-nicardipine binding to sections
      of human pulmonary artery was consistent with the labeling of Ca2+ channels of
      the L-type. It was similar in the pulmonary artery and in the human renal and
      right coronary arteries. Light microscope autoradiography revealed a high density
      of [3H]-nicardipine binding sites within smooth muscle of the tunica media of
      human pulmonary artery as well as of human renal and right coronary arteries. A
      lower accumulation of the radioligand occurred in the tunica adventitia. No
      specific binding was noticeable in the tunica intima. Our data suggest that human
      pulmonary artery expresses Ca2+ channels of the L-type sensitive to
      dihydropyridines. These sites have similar affinity and lower density than those
      expressed by systemic arteries. The presence of Ca2+ channels of the L-type in
      human pulmonary artery suggests that their pharmacological manipulation may be
      considered in the treatment of pulmonary hypertension.

PMID- 9607403
TI  - Effect of weight loss on resting energy expenditure in hypertensive and
      normotensive obese women.
AB  - Hyperinsulinemia and the associated increased sympathetic nervous activity have
      been proposed to implicate in the development of hypertension and obesity. The
      role of hyperinsulinemia in mediated resting energy expenditure (REE) in
      hypertensive obese subjects is not clear. The effect of weight loss on REE
      between hypertensive and normotensive obese women are also unknown. We measured
      fasting plasma glucose, insulin, lipids concentrations, REE and body composition
      by bioelectrical impedance methods before and after a weight loss program in 9
      newly diagnosed hypertensive and 10 normotensive obese women. As compared with
      age-matched lean control women (n=14), obese subjects had higher fasting plasma
      glucose, insulin concentrations and REE values. However, these variables were not
      different between obese groups. Although REE and fasting plasma insulin
      concentrations correlated well in simple correlation (r=0.708, p<0.001), this
      relationship disappeared after adjusting for values of fat free mass (FFM).
      Weight loss for approximately 10% of initial weight led to significant decreases
      of blood pressure and fasting plasma insulin concentrations in both obese groups.
      Fasting plasma cholesterol, LDL cholesterol and triglyceride concentrations
      decreased in hypertensive obese individuals. Significant fall of REE in
      hypertensive group (p<0.05) and normotensive group (p<0.02) were observed
      following weight loss. However, the ratio of REE to FFM decreased significantly
      only in hypertensive subjects (114.6+/-5.2 KJ/day x Kg(-1) to 107.2+/-4.6 KJ/day
      x Kg(-1), p<0.05). In conclusion, obese women, either hypertensive or
      normotensive, had higher fasting plasma insulin concentrations and REE than those
      of lean controls, although these variables were not different between obese
      groups. No significant relation between fasting plasma insulin and REE could be
      found. Weight loss produced a significant decrease of REE/FFM only in
      hypertensive obese women. Further study to evaluate the effect of weight loss on
      energy expenditure in hypertensive obese subjects is necessary.

PMID- 9607404
TI  - Endothelin converting-enzyme-1 mRNA expression in human cardiovascular disease.
AB  - Endothelin-1 converting-enzyme (ECE-1) cleaves the precursor, big-endothelin-1,
      to the active peptide endothelin-1. The aim of this study was to investigate
      whether ECE-1 mRNA expression is modified in human cardiovascular disease. Tissue
      samples from the left human atrium were analyzed for ECE-1 expression and related
      to different clinical parameters. A quantitative PCR assay (qPCR) with
      competitive and non-competitive standards was established. The ECE-1 measurements
      were normalized by a GAPDH qPCR. Patients who suffered from a myocardial
      infarction had elevated ECE-1 levels when compared to controls (5.81+/-0.76 vs.
      3.20+/-0.51 fg ECE-1, ng GAPDH, p<0.05). Drug treatment with the beta-blocker
      metoprolol was associated with a decreased ECE-1 expression level (3.90+/-0.58
      vs. 5.81+/-0.76 fg ECE-1, ng GAPDH, p<0.1). We conclude that the expression of
      ECE-1 is altered in the atrial tissue depending on the physiological status of
      the heart. This suggests a differential role of ECE-1 in cardiovascular diseases.

PMID- 9607405
TI  - Significant role of the increase in renin-angiotensin system in cardiac
      hypertrophy and renal glomerular sclerosis in double transgenic tsukuba
      hypertensive mice carrying both human renin and angiotensinogen genes.
AB  - Tsukuba hypertensive mice (THM) are a hypertensive model prepared by mating a
      transgenic mice with human renin gene and a transgenic mice with human
      angiotensinogen gene. In the present study, we examined effects of renin
      angiotensin system (RAS) on cardiac hypertrophy and renal disorders using Tsukuba
      hypertensive mice. While THM showed an increase of about 30 mmHg in systolic
      pressure compared to C57BL/6 mice employed as normal control animals, the
      increase in blood pressure was not observed in the mice to which either gene was
      transferred. Urinary volume, water intake volume, urinary albumin excretion,
      heart to body weight ratio and renal glomerular sclerosis index increased
      significantly in THM, but none of these parameters showed a significant
      difference from the C57 mice when they were examined in mice to which either of
      the genes was transferred. In contrast, when lisinopril was administered to THM,
      all the parameters decreased significantly without lowering the systolic
      pressure. From these findings, it was demonstrated that RAS was playing a
      significant role in cardiac hypertrophy and renal disorders of THM and that
      lisinopril had inhibitory effects on cardiac hypertrophy and renal glomerular
      sclerosis by inhibiting RAS.

PMID- 9607406
TI  - Effect of head-out water immersion on serum sodium transport inhibitor and
      urinary nonadrenaline excretion in pre-menopausal women.
AB  - The effect of head out water immersion on the excretion of catecholamines and
      serum sodium transport inhibitor (STI) was studied in healthy young women during
      the follicular and leuteal phases. Two way ANOVA showed that menstrual cycle had
      no effect on the excretion of noradrenaline (NA), dopamine (DA) or serum STI.
      Analysis of pooled data from follicular and leuteal phases showed that immersion
      caused a significant increase in sodium excretion and serum STI and a significant
      decrease in urinary NA excretion in healthy young women. After immersion, sodium
      excretion, DA excretion and serum STI decreased and NA increased.

PMID- 9607407
TI  - Angiotensin II AT1 receptor/signaling mechanisms in the biphasic effect of the
      peptide on proximal tubular Na+,K+-ATPase.
AB  - The present study was designed to determine the cellular signaling mechanisms
      responsible for mediating the effects of angiotensin II on proximal tubular
      Na+,K+-ATPase activity. Angiotensin II produced a biphasic effect on Na+,K+
      ATPase activity: stimulation at 10(-13) - 10(-10) M followed by inhibition at 10(
      7) - 10(-5) M of angiotensin II. The stimulatory and inhibitory effects of
      angiotensin II were antagonized by losartan (1nM) suggesting the involvement of
      AT1 receptor. Angiotensin II produced inhibition of forskolin-stimulated cAMP
      accumulation at 10(-13) - 10(-10) M followed by a stimulation in basal cAMP
      levels at 10(-7) - 10(-5) M. Pretreatment of proximal tubules with losartan (1nM)
      antagonized both the stimulatory and inhibitory effects of angiotensin II on cAMP
      accumulation. Pretreatment of the proximal tubules with pertussis toxin (PTx)
      abolished the stimulation of Na+,K+-ATPase activity but did not affect the
      inhibition of Na+,K+-ATPase activity produced by angiotensin II. Pretreatment of
      the tubules with cholera toxin did not alter the biphasic effect of angiotensin
      II on Na+,K+-ATPase activity. Mepacrine (10microM), a phospholipase A2 (PLA2)
      inhibitor, reduced only the inhibitory effect of angiotensin II on Na+,K+-ATPase
      activity. These results suggest that the activation of AT1 angiotensin II
      receptors stimulates Na+,K+-ATPase activity via a PTx-sensitive G protein-linked
      inhibition of adenylyl cyclase pathway, whereas the inhibition of Na+,K+-ATPase
      activity following AT1 receptor activation involves multiple signaling pathways
      which may include stimulation of adenylyl cyclase and PLA2.

PMID- 9607408
TI  - "Tet-on": a gene switch for the exogenous regulation of transgene expression.

PMID- 9607409
TI  - Oligoplexes: nonviral vehicles for receptor-mediated delivery.

PMID- 9607410
TI  - Intravenous RMP-7 increases delivery of ganciclovir into rat brain tumors and
      enhances the effects of herpes simplex virus thymidine kinase gene therapy.
AB  - Herpes simplex virus thymidine kinase (HSV-tk) gene therapy for brain tumors
      depends on ganciclovir (GCV) and its transport across the blood-brain tumor
      barrier (BBTB). We examined whether RMP-7, the bradykinin analog and potent BBTB
      permeabilizer, could enhance the efficacy of GCV treatment of brain tumors by
      increasing the BBTB delivery of GCV. In vitro, a significant bystander cytocidal
      effect of GCV was shown in mixed HSV-tk-transduced (HSV-tk+) and control vector
      transduced (HSV-tk-) C6 glioma cultures. A dose-dependent cytotoxic effect of GCV
      on untransformed C6 cells was also shown. In vivo, rats with 100% HSV-tk+ or 100%
      HSV-tk- intracerebral C6 gliomas were treated for 7 days with intravenous
      infusions of GCV alone or with GCV and RMP-7 (2.5 microg/kg/day). The growth of
      HSV-tk+ and HSV-tk- gliomas decreased with increasing doses of GCV. A high dosage
      (100 mg of GCV/kg/day) eradicated all HSV-tk- and HSV-tk+ tumors. An intermediate
      dosage (5 mg of GCV/kg/day) reduced the growth of HSV-tk- gliomas by 42% if given
      alone, and by 88% in combination with RMP-7. A low dosage (0.5 mg of GCV/kg/day)
      in combination with RMP-7 enhanced the regression of HSV-tk+ gliomas by 87%
      compared with GCV alone. Low-dose GCV was ineffective in HSV-tk- tumors. RMP-7
      increased [3H] GCV tumoral uptake by 2.6- and 1.7-fold in the tumor center and
      periphery, respectively. We conclude that RMP-7 could be an important adjunctive
      treatment for suicide gene therapy of brain tumors, while an RMP-7/GCV
      combination may also have a significant antitumor effect in untransfected
      gliomas.

PMID- 9607411
TI  - Dose-dependent doxycycline-mediated adrenocorticotropic hormone secretion from
      encapsulated Tet-on proopiomelanocortin Neuro2A cells in the subarachnoid space.
AB  - We previously reported that polymer-encapsulated mouse neuroblastoma cells that
      are capable of secreting beta-endorphin may reduce pain sensitivity in rats after
      capsule implantation into the cerebrospinal fluid (CSF)-filled subarachnoid space
      of the spinal cord. The neuroblastoma cells carry the proopiomelanocortin (POMC)
      gene that encodes the precursor of adrenocorticotropic hormone (ACTH) and beta
      endorphin. To control the expression of these hormones in the present study, a
      promoter that is inducible by administration of tetracycline derivatives such as
      doxycycline (Dox) was linked to the POMC gene. Encapsulated cells in the CSF
      space of rats stimulated by four intraperitoneal doses of Dox responded with ACTH
      expression as determined in a subsequence 36-hr in vitro incubation. The amount
      of ACTH released was dependent on the in vivo Dox dose. These findings indicate
      that gene expression in xenogeneic cells in the CSF space can be manipulated by
      injection of a relatively innocuous drug, and suggest that this system may be
      applicable to cell transplantation therapy in patients with central nervous
      system diseases that require temporary control of ligand delivery.

PMID- 9607412
TI  - Decoy administration of NF-kappaB into the subarachnoid space for cerebral
      angiopathy.
AB  - Subarachnoid hemorrhage (SAH), encephalitis, meningitis, and autoimmune diseases
      sometimes lead to cerebral angiopathy, characterized specifically by narrowing of
      vessels, morphological changes in the structure of vessel walls, and a
      concomitant decrease in cerebral blood flow. Many patients also develop delayed
      ischemic neurological deficits. Thus, preventing vascular reactions is of
      paramount importance in treating SAH. Although cerebral vasospasm has some
      relationship with the inflammatory reaction of major cerebral vessels against the
      autologous blood, and many trials have attempted to prevent angiopathy after SAH,
      an effective treatment has not yet been established. The purpose of this article
      is to evaluate the preventive effect of nuclear factor KB (NF-kappaB) decoy oligo
      DNA after SAH; since NF-kappaB is closely related to inflammation. In the rabbit
      angiopathy model after SAH, we evaluated the effectiveness of the decoy oligo-DNA
      using the angiographic (digital subtraction angiography) and histological
      (hematoxylin-eosin and Masson's trichrome staining) methods. Moreover, a gel
      shift assay for NF-kappaB was also performed in order to evaluate the activity of
      NF-kappaB. We describe a new concept for treating cerebral angiopathy after SAH
      and for successfully inhibiting cerebral vasospasm and morphological changes in
      vessel walls in a rabbit model. In this treatment, we used synthetic double
      strand oligo-DNA with a high affinity for transcription factor NF-kappaB, and
      cationic liposome complex administered through the cerebrospinal fluid.

PMID- 9607413
TI  - Effects of poloxamer 407 on transfection time and percutaneous adenovirus
      mediated gene transfer in native and stented vessels.
AB  - Reduction in transfection time and the ability to perform gene transfer in
      conjunction with endovascular stent implantation constitute two important
      challenges for percutaneous adenovirus-mediated gene transfer to vessel walls.
      Studies have suggested that the use of biocompatible polyol poloxamer 407 could
      be useful. We first evaluated the use of poloxamer 407 for percutaneous gene
      transfer in nonstented rabbit iliac arteries. A 200-microl mixture of Ad
      RSVbetagal or Ad-CMVLuc in either phosphate-buffered saline (PBS) or 20%
      poloxamer was delivered. After 3 days, gene transfection was evaluated by X-Gal
      staining or measurement of luciferase activity. Poloxamer use resulted in a 3- to
      15-fold increase in the percentage of transfected cells (X-Gal, p = 0.001) and a
      16-fold increase in protein product (luciferase activity, p = 0.03), and allowed
      a decrease in transfection time from 30 to 5 min with minimal reduction in
      transfection efficiency. We then evaluated the feasibility of percutaneous gene
      transfer, using Ad-RSVbetagal diluted in pure PBS or 20% poloxamer, in
      conjunction with stent implantation. Gene delivery was performed either
      immediately before (pre-) or after (post-) stent implantation. When adenoviruses
      were diluted in PBS, gene transfer had a low efficiency (prestent, 0.3%;
      poststent, 0.2%; NS). With poloxamer, the efficacy was much higher (p = 0.0001)
      and similar "pre" (2.2%) or "post" (1.7%) stent delivery (NS). CONCLUSIONS: (1)
      The use of poloxamer, rather than PBS, as a vehicle increases the efficacy of
      percutaneous adenovirus-mediated gene transfer and reduces transfection time; (2)
      gene transfer performed during stent implantation with poloxamer is feasible and
      achieves a significant level of gene expression. Thus percutaneous gene delivery
      is applicable to conventional stents and could present an attractive method by
      which to achieve local biological effects in a stent environment.

PMID- 9607414
TI  - Retroviral transfer and long-term expression of the adrenoleukodystrophy gene in
      human CD34+ cells.
AB  - Adrenoleukodystrophy (ALD) is a demyelinating disease of the central nervous
      system that results from a genetic deficiency of ALDP, an ABC protein involved in
      the transport of very long-chain fatty acids (VLCFAs). The cloning of the ALD
      gene and the positive effects of allogeneic bone marrow transplantation support
      the feasibility of a gene therapy approach. We report the retroviral transfer of
      the ALD cDNA to peripheral blood and bone marrow CD34+ cells from control donors
      and ALD patients. Prestimulation of these cells with cytokines, followed by
      infection with the M48-ALD retroviral vector, resulted in 20% transduction
      efficiency (4-40%) and expression of the vector-encoded ALDP in 20% of CD34+
      cells (7.3-50%). Long-term culture (LTC) of transduced CD34+ cells from two ALD
      patients showed efficient transduction (24-28%) and stable expression (25-32%) of
      ALDP in derived clonogenic progenitors at 3 weeks of culture. The expression of
      ALDP in CFU cells derived from 5 and 6 weeks of LTC confirmed the effective
      transduction of LTC-initiating cells. Expression of ALDP was observed in CD68+
      CFU-derived cells, suggesting that monocyte-macrophages, the target bone marrow
      cells in ALD, were produced from transduced progenitor cells. VL-CFA content was
      corrected in LTC and CFU-derived cells in proportion to the percentage of
      transduced cells, indicating that the vector-encoded ALDP was functional.
      Although not efficient yet to allow a clinical perspective, these results
      demonstrate the feasibility of ALD gene transfer into CD34+ cells of ALD
      patients.

PMID- 9607415
TI  - An RGD-oligolysine peptide: a prototype construct for integrin-mediated gene
      delivery.
AB  - We have synthesized a linear, bifunctional peptide that comprises an integrin
      targeting domain containing an arginine-glycine-aspartic acid tripeptide motif
      and a DNA-binding moiety consisting of a short stretch of 16 lysine residues.
      This peptide can form distinctive, condensed complexes with DNA and is capable of
      mediating its delivery and expression in a variety of mammalian cells in culture.
      Internalization is mediated by cell surface integrin receptors via a mechanism
      that is known to be phagocytic. We have analyzed the relationship between DNA and
      peptide and have investigated the conditions suitable for optimal gene delivery.
      The formation of condensed peptide DNA complexes leads to resistance to nuclease
      degradation. The level of reporter gene expression obtained is dependent on the
      peptide-to-DNA ratio and is enhanced in the presence of the endosomal buffer
      chloroquine, polyethyleneimine, and deactivated adenovirus during gene delivery.
      Under optimal conditions the levels of reporter gene expression obtained approach
      or even exceed those obtained with DNA delivered with the commercial liposome
      Lipofectamine. The ability to produce an efficient gene delivery system using
      small, easily modified, and well-defined constructs that have no constraint of
      particle size demonstrates the advantages of integrin-targeting peptides for gene
      transfer.

PMID- 9607416
TI  - Recombinant adeno-associated virus for the generation of autologous, gene
      modified tumor vaccines: evidence for a high transduction efficiency into primary
      epithelial cancer cells.
AB  - To explore the potential of recombinant vectors based on recombinant adeno
      associated virus (rAAV) for cancer vaccination, we investigated the transduction
      efficiency of rAAV into cancer cells ex vivo. Infection of human epithelial
      cancer cell lines with rAAV carrying reporter genes encoding beta-galactosidase
      (rAAV/LacZ) or luciferase (rAAV/Luc) resulted in high levels of reporter gene
      expression (>90% positive cells). In marked contrast, rAAV poorly transduced all
      murine tumor cell lines, as well as human hematopoietic cell lines. Either
      irradiation or adenovirus infection of tumor cells prior to rAAV infection
      induced a 10- to 100-fold increase of reporter gene expression. To determine the
      transduction efficiency of rAAV into primary cancer cells, freshly isolated,
      irradiated tumor cells from malignant melanoma and ovarian carcinoma patients
      were infected with rAAV/Luc, resulting in up to 6.9-fold higher levels of gene
      expression than in a HeLa tumor cell line. Time course experiments with freshly
      isolated tumor cells infected with rAAV/Luc showed maximal levels of luciferase
      expression between days 3 and 9 posttransduction. Simultaneous infection of
      primary tumor cells with up to three rAAV vectors containing genes encoding the
      immunostimulatory proteins B7-2 (CD86), p35 subunit of IL-12, and p40 subunit of
      IL-12 resulted in high expression of B7-2 in more than 90% of the tumor cells and
      in the secretion of high levels of IL-12. Taken together, our results demonstrate
      that rAAV efficiently transduces freshly isolated human, epithelial tumor cells
      and might therefore be a potent tool to produce improved, gene-modified cancer
      vaccines.

PMID- 9607417
TI  - The influence of patient-related factors on ex vivo retroviral-mediated gene
      transfer into mobilized peripheral blood myeloid progenitors.
AB  - Mobilized human peripheral blood progenitor cells are potential alternatives to
      bone marrow cells as targets for ex vivo gene transfer. We report the
      transduction efficiency of retroviral-mediated gene transfer into myeloid
      progenitors of peripheral blood progenitor cell (PBPC) harvests, mobilized by
      high-dose cyclophosphamide and GM-CSF, compared with nonmobilized bone marrow
      (BM). Eleven PBPC samples were enriched for CD34+ cells, preincubated with IL-3
      (10 ng/ml), IL-6 (50 ng/ml), and 10% autologous plasma for 42 hr, and transduced
      over a 6-hr incubation with IL-3 + IL-6 and a retroviral vector carrying the NeoR
      gene. NeoR-specific sequences were detected by polymerase chain reaction in 10
      cell pellets (91%). Gene expression in CFU-GM colonies was found in nine
      transduced samples (82%), with a mean transduction efficiency of 5.2% (95% CI,
      1.3-11.8%) CFU-GM per PBPC sample. In univariate analysis, a higher transduction
      efficiency into CFU-GM correlated significantly with a higher CFU-GM
      concentration in the CD34+-enriched sample (p = 0.009), a shorter interval from
      diagnosis (p < 0.001), and fewer months of prior cytotoxic treatment (p = 0.001);
      correlation with younger age was of borderline statistical significance (p =
      0.077). In multivariate analysis a shorter interval from diagnosis and, to a
      lesser degree, a higher CFU-GM concentration in the CD34+-enriched sample were
      independent predictors of higher transduction efficiency. Twelve BM samples were
      similarly transduced; 11 pellets were PCR positive. CFU-GM NeoR gene expression
      was 4.2% (95% CI, 2.0-7.2%) CFU-GM per BM sample, which was not significantly
      different from the transduction efficiency into PBPC cells. No correlation was
      found between the transduction efficiency of CFU-GM in BM samples and CFU-GM
      concentration in the CD34+-enriched sample, time from diagnosis, months of prior
      cytotoxic treatment, and/or patient age. Our data suggest that the transduction
      efficiency ex vivo may be influenced by time from diagnosis, CFU-GM concentration
      in the sample, and possibly by the extent of prior cytotoxic administration.

PMID- 9607418
TI  - Enhancement of the functional repertoire of the rat parietal peritoneal
      mesothelium in vivo: directed expression of the anticoagulant and
      antiinflammatory molecule thrombomodulin.
AB  - We have used our previously described ex vivo mesothelial cell (MC)-mediated gene
      therapy strategy (Gene Ther. 2:393-401, 1995) to modify the functional properties
      of the rat parietal peritoneal mesothelium in vivo by expression of a membrane
      bound recombinant protein on the MC surface. Rat primary MCs were stably
      transfected (using strontium phosphate DNA coprecipitation) with a plasmid
      containing the gene for rat thrombomodulin (TM), a transmembrane glycoprotein
      that functions as an essential cofactor for the physiological activation of the
      anticoagulant protein C by the enzyme thrombin. As demonstrated by
      immunohistochemistry and by direct equilibrium binding with radiolabeled
      thrombin, genetically modified MCs expressed high levels of TM antigen on their
      surface in vitro. As judged by a thrombin-dependent protein C activation assay,
      such MC membrane-bound TM was biologically active. Once reseeded on the denuded
      parietal peritoneal surface of syngeneic recipients, these TM-transfected MCs
      continued to express TM antigen in vivo for at least 90 days. Moreover, the
      recombinant TM expressed on the reconstituted parietal mesothelium retained its
      ability to activate protein C in a thrombin-dependent manner. Our data indicate
      that MC-mediated expression of TM can be used to augment the anticoagulant
      properties of the parietal peritoneal surface. In general, our results suggest
      that ex vivo MC-mediated gene therapy can be used to deliver other therapeutic
      transmembrane proteins to the MC surface to enhance the functional repertoire of
      the parietal mesothelium in vivo.

PMID- 9607419
TI  - Adenovirus-mediated herpes simplex virus thymidine kinase/ganciclovir gene
      therapy in patients with localized malignancy: results of a phase I clinical
      trial in malignant mesothelioma.
AB  - Malignant pleural mesothelioma is a fatal neoplasm that is unresponsive to
      standard modalities of cancer therapy. We conducted a phase I dose-escalation
      clinical trial of adenoviral (Ad)-mediated intrapleural herpes simplex virus
      thymidine kinase (HSVtk)/ganciclovir (GCV) gene therapy in patients with
      mesothelioma as a model for treatment of a localized malignancy. The goals of
      this phase I trial were to assess the safety, toxicity, and maximally tolerated
      dose of intrapleural Ad.HSVtk, to examine patient inflammatory response to the
      viral vector, and to evaluate the efficiency of intratumoral gene transfer.
      Twenty-one previously untreated patients were enrolled in this single-arm, dose
      escalation study with viral doses ranging from 1 x 10(9) plaque-forming units
      (pfu) to 1 x 10(12) pfu. A replication-incompetent recombinant adenoviral vector
      containing the HSVtk gene under control of the Rous sarcoma virus (RSV) promoter
      enhancer was introduced into the pleural cavity of patients with malignant
      mesothelioma followed by 2 weeks of systemic therapy with GCV at a dose of 5
      mg/kg twice a day. The initial 15 patients underwent thoracoscopic pleural biopsy
      prior to, and 3 days after, vector delivery. The last six patients underwent only
      the post-vector instillation biopsy. Dose-limiting toxicity was not reached. Side
      effects were minimal and included fever, anemia, transient liver enzyme
      elevations, and bullous skin eruptions, as well as a temporary systemic
      inflammatory response in those receiving the highest dose. Strong intrapleural
      and intratumoral immune responses were generated. Using RNA PCR, in situ
      hybridization, immunohistochemistry, and immunoblotting, HSVtk gene transfer was
      documented in 11 of 20 evaluable patients in a dose-related fashion. This study
      demonstrates that intrapleural administration of an adenoviral vector containing
      the HSVtk gene is well tolerated and results in detectable gene transfer when
      delivered at high doses. Further development of therapeutic trials for treatment
      of localized malignancy using this vector is thus warranted.

PMID- 9607420
TI  - Significant behavioral recovery in Parkinson's disease model by direct
      intracerebral gene transfer using continuous injection of a plasmid DNA-liposome
      complex.
AB  - As an alternative to virus-mediated gene transfer, we previously demonstrated a
      simple, safe, and efficient transfer of foreign gene into the central nervous
      system using continuous injection of a plasmid DNA-cationic liposome complex. To
      explore whether this approach can be applied to the treatment of certain
      neurological disorders, we used an experimental model of Parkinson's disease (PD)
      in the present study. Following continuous injection for 7 days, tyrosine
      hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC) genes carried by
      a bovine papilloma virus-based plasmid vector were efficiently introduced into
      glial cells in the striatum of 6-hydroxydopamine-lesioned rats. Significant
      recovery in apomorphine-induced rotational behavior of PD models was obtained by
      transfection of TH gene and this effect continued for up to 5 weeks after
      injection. Moreover, cotransfection of TH with AADC genes was readily
      accomplished by this procedure and resulted in a greater and longer-lasting
      improvement of apomorphine-induced rotational behavior than was achieved by
      transfection of TH gene alone. We suggest that this approach is a controllable
      and manageable alternative to other methods of gene therapy for the treatment of
      PD.

PMID- 9607421
TI  - Enhanced green fluorescent protein as an efficient reporter gene for retroviral
      transduction of human multipotent lymphoid precursors.
AB  - Owing to its autofluorescence properties, green fluorescent protein (GFP) has
      aroused increasing interest as a marker system for many research applications. In
      this study we investigated the suitability of the "enhanced" GFP (EGFP), a mutant
      version of GFP optimized for flow cytometry and microscopy detection, as a
      reporter gene for retroviral transduction protocols. EGFP was shown to display a
      bright and stably maintained emission pattern in transfected GP+envAm12 packaging
      cells. Stable fluorescent emission was observed as well after transduction in NIH
      3T3 fibroblasts and in the human Jurkat T cell line, in which EGFP was shown to
      confer no deleterious effect or growth disadvantage on the expressing cells.
      Moreover, EGFP expression could be detected after short-term retroviral exposure,
      thus allowing a rapid and quantitative retroviral titering assay, alternative to
      the standard colony-formation procedure. Most importantly, we showed the
      feasibility of EGFP as a marker gene in retroviral-mediated transduction of
      primary lymphoid precursors. In particular, transduction of CD34+CD1- human
      thymocytes by short-term cocultivation yielded up to 30% of EGFP-expressing
      cells, while maintaining CD34 expression levels. Finally, when cultured under
      multicytokine-supported conditions, such transduced intrathymic progenitors were
      shown to efficiently generate lymphoid-related dendritic cells, which displayed a
      distinct EGFP expression. Therefore, because of its rapid and easy detectability
      and its nontoxic characteristics, EGFP proves itself to be a valuable reporter
      gene by allowing the transduction of multipotential progenitors and by being
      compatible with the developmental programs of lymphoid lineage generation.

PMID- 9607422
TI  - Stratification of treatment of stage 4 neuroblastoma patients based on N-myc
      amplification status. Study Group of Japan for Treatment of Advanced
      Neuroblastoma, Tokyo, Japan.
AB  - BACKGROUND: It has been shown that children aged more than 12 months with stage 3
      and 4 neuroblastoma with N-myc amplification do worse than those without
      amplification. Development of an innovative chemotherapeutic protocol for
      patients in such an extremely poor-risk group was the purpose of this study.
      PROCEDURE: Since March 1991 a new protocol for the treatment of advanced
      neuroblastoma was started. When N-myc was amplified more than 10-fold, patients
      received regimen A3, in which cyclophosphamide 1,200 mg/m2 was given on days 1
      and 2; hence the dose of cytotoxic drugs was doubled. Patients with fewer than 10
      copies of N-myc received regimen new A1, which is very similar to regimen A1 that
      had been used until March 1991 for all patients with advanced neuroblastoma
      with/without N-myc amplification. The efficacy of regimen A3 was evaluated.
      RESULTS: The relapse-free survival rate at 1 and 2 years for stage 4 patients
      older than 12 months of age with N-myc amplification of more than 10-fold was 43%
      and 29%, respectively, with regimen A1 and that for the same subgroup of patients
      treated with regimen A3 since March 1991 was 79% and 49%, respectively; the
      difference is statistically significant. On the other hand, there were no
      differences in the relapse-free survival rate at 1 year and 2 years for stage 4
      patients with fewer than 10 copies of N-myc between those treated with regimen A1
      and those treated with new A1 since March 1991. CONCLUSIONS: Stratification based
      on N-myc amplification into new A1 and A3 treatment protocols is of significant
      clinical importance. Regimen A3 was well tolerated and showed an improvement in
      clinical results in stage 4 patients with N-myc amplified more than 10-fold.

PMID- 9607423
TI  - Teratomas in infancy and childhood.
AB  - BACKGROUND AND PROCEDURE: Outcomes in children with teratomas collected between
      October 1982 and December 1995 in cooperative protocols of the German Society of
      Pediatric Oncology and Hematology (GPOH) were analyzed. Teratomas were diagnosed
      in 329 (42%) of 780 registered patients with germ cell tumors. The annual
      incidence was 0.24/100,000. Main primary sites were coccygeal (n = 132, 2.2:1
      female predominance), ovary (n = 81), testis (n = 40) and brain (n = 15, 2.8:1
      male predominance). RESULTS: Two hundred seventy cases of extracranial non
      testicular teratoma were evaluated: In mature teratomas (n = 154) the observed
      relapse rate was 10%. Incomplete resection was the main risk factor for relapse.
      After complete resection, the relapse-free survival (RFS, Kaplan-Meier
      estimation) was 0.96 +/- 0.01 (n = 126, observation time 18-155 months) in
      comparison to an RFS of 0.56 +/- 0.09 in incompletely resected teratomas grade 0
      (n = 28, observation time 28-94 months) (P < 0.01). Im-mature teratomas were
      treated by surgery alone in 76 cases and by surgery and adjuvant chemotherapy in
      40 cases. The observed relapse risk was 18%. Main risk factors for relapse were
      incomplete tumor resection (n = 38) as well as immaturity in incompletely
      resected teratomas. Fifteen of 29 relapsing patients presented with malignant
      tissue in the recurrent tumor (mainly yolk sac tumor); in contrast, seven of 40
      patients with immature teratoma relapsed despite adjuvant chemotherapy without
      showing malignant components (P = 0.014). Nine of 36 (25%) relapsing patients
      died of disease. Eleven of the 27 (41%) surviving children suffered from
      mutilation after repeated surgery. COMMENTS: It is suggested that an
      international randomized trial for patients with incompletely resected high risk
      teratoma be initiated to evaluate the effect of adjuvant chemotherapy on specific
      end-points: 1) influence on relapse rate in general; 2) reduction of the
      proportion of malignant relapses; 3) avoidance of mutilating surgery.

PMID- 9607424
TI  - Treatment of adults with progressive oligodendroglioma with carboplatin (CBDCA):
      preliminary results. Writing Committee for The Brain Tumor Center at Duke.
AB  - BACKGROUND: Exploration of the role of chemotherapy in the treatment of low grade
      glioma, including oligodendroglioma, has been limited to the pediatric
      population, reflecting the sensitivity of young patients to radiation-induced
      toxicity and a desire to avoid this intervention (7-12). PROCEDURE: Nine adults
      with progressive oligodendroglioma were treated with carboplatin at a dose of 560
      mg/m2 administered at 4 week intervals. RESULTS: Eight patients have demonstrated
      stable disease as determined by serial MRI imaging at 2-3 month intervals with
      neither tumor regression nor growth noted. The ongoing duration of tumor control
      ranges between 6-22 months. Three patients have completed therapy with
      carboplatin and continue with stable dis-ease off chemotherapy. One patient
      progressed after 1 year of therapy with histologic confirmation of growth of well
      differentiated oligodendroglioma. Toxicity was limited to grade 3
      thrombocytopenia in 3 patients and grade 3 neutropenia in 2 patients.
      CONCLUSIONS: Carboplatin appears to be active in the treatment of adults with
      progressive oligodendroglioma. Further trials are warranted to more precisely
      define the role of carboplatin in the treatment of these tumors.

PMID- 9607425
TI  - Brain abscesses in children with cancer.
AB  - BACKGROUND: Brain abscesses in pediatric patients are rare events, and the
      causative organism and prognosis vary with the population under study. Children
      with cancer seem to be particularly susceptible to the development of brain
      abscesses because of the immunological changes induced by cancer and its
      treatment. We reviewed the records of children who developed a brain abscess
      during treatment of a malignancy to define the clinical characteristics,
      prognosis, and management of these patients. PROCEDURE: We performed a
      retrospective review of the clinical and laboratory characteristics of all cancer
      patients younger than age 20 years who were admitted to our institution between
      1980 and 1996 for a brain abscess. RESULTS: Twelve children were identified.
      Cancer diagnoses were brain tumor in two, systemic PNET in two, and leukemia in
      eight. Six patients had multiple abscesses. Eleven received prior chemotherapy.
      Abscesses were surgically excised or aspirated in seven, and empiric antibiotics
      were given to the other five. At surgery, Listeria monocytogenes, Aspergillus
      fumigatus (3), Fusarium, and Candida lusitanea were cultured. Aspergillus was
      identified in other locations in four patients. Abscesses were successfully
      treated in seven patients, two of whom received antibiotics only; five patients
      (42%) died from infection. CONCLUSIONS: Mortality is high in this
      immunosuppressed population, in part due to the preponderance of fungal
      infection. The finding of very rare organisms suggests that drainage and culture
      should be performed whenever possible; empiric antibiotics that include an
      antifungal agent may, on occasion, be successful.

PMID- 9607426
TI  - Role of 131I-metaiodobenzylguanidine in the treatment of neuroblastoma.
AB  - BACKGROUND: Standard chemo-radiotherapy methods for the treatment of children
      with advanced neuroblastoma (NBL) including bone marrow transplant approaches
      have been disappointing. These poor results can be ascribed to the evolution of
      residual drug-resistant cell populations. Curative attempts should therefore be
      directed to their elimination during induction treatment. This can best be
      accomplished through the use of multiple, non-cross-resistant agents early in
      therapy. 131I-Metaiodobenzylguanidine (131I-MIBG) provides a mechanism for the
      delivery of high doses of radiation to NBL lesions. Experience reported from
      several institutions indicates an approximate 50% response rate in previously
      treated children with advanced NBL. CONCLUSIONS: A better strategy is to employ
      131I-MIBG together with intensive chemotherapy at the time of diagnosis. A pilot
      study adopting these principles and supported by laboratory data has been
      designed and is underway.

PMID- 9607427
TI  - Alkalinization and the tumor lysis syndrome.

PMID- 9607428
TI  - Silhouette. Frank Ellis, M.S., M.D., FRCP, FRCR.

PMID- 9607429
TI  - Management of extraosseous ewing sarcoma of the infratemporal fossa.

PMID- 9607430
TI  - Acute lymphoblastic leukemia of Burkitt type (L3 ALL) with t(8;14) lacking
      surface and cytoplasmic immunoglobulins.

PMID- 9607431
TI  - Use of pamidronate in the management of acute cancer-related hypercalcemia in
      children.

PMID- 9607432
TI  - Occurrence of an acute Fanconi syndrome following cisplatin chemotherapy.

PMID- 9607433
TI  - Pneumoperitoneum produces reversible renal dysfunction in animals with normal and
      chronically reduced renal function.
AB  - Laparoscopic surgery with intraperitoneal insufflation is associated with acute
      oliguria. Although in healthy patients, this impairment is transient and without
      any apparent sequelae, as the scope of laparoscopic surgery expands, subtle renal
      injury may become clinically significant, particularly when applications expand
      to patients with reduced baseline renal function. We have investigated the
      changes in renal function during and after pneumoperitoneum in animals with
      reduced renal mass to identify both acute alterations and long-term impairments,
      if any. Twelve swine underwent surgical reduction in renal mass to produce
      chronic renal insufficiency. Glomerular filtration rate (GFR) was determined by
      inulin clearance for each animal before and after ablation to establish the
      degree of renal impairment (mean 22%; range 18%-31% of normal). The animals were
      followed during a stepwise insufflation as a study of pneumoperitoneum-induced
      changes in chronic renal failure. Urine output declined dramatically (-80% at 20
      mm Hg), the GFR fell (-63% at 20 mm Hg), and renal blood flow declined (mean 
      12%; range -9% to -19%) over the course of the test. These values did not return
      to baseline during a 90-minute observation period after release of the
      pneumoperitoneum. Acute renal failure occurred despite aggressive hydration with
      maintenance of central venous pressure and only modest changes in cardiac output.
      The animals were exposed to a 6-hour CO2 pneumoperitoneum to 20 mm Hg to model
      the insult of complex laparoscopy. This exposure resulted in elevation of the
      amount of N-methyl-beta-D-glucosaminidase being shed into the urine in addition
      to the previously indicated impairments. The animals were allowed to recover for
      1 week, and then GFR was again measured. The GFR returned to the preexposure
      chronic renal failure levels for both the group as a whole and individual
      animals. The magnitude and duration of the alteration in urine output, GFR, and
      renal blood flow suggest that regulatory mechanisms rather than simple mechanical
      forces are involved in the acute changes. No long-term impact on renal function
      from the acute renal injury was identified, even in animals with existing renal
      insufficiency.

PMID- 9607434
TI  - Bacterial biofilm formation, encrustation, and antibiotic adsorption to ureteral
      stents indwelling in humans.
AB  - Encrustation and urinary tract infection are problematic complications of
      ureteral stent usage. The objective of our first study was to use surface science
      techniques to examine three ureteral stent types for encrustation, biofilm
      formation, and antibiotic adsorption after use in patients. Black Beauty (N =
      16), LSe (N = 16), and SofFlex (N = 32) ureteral stents were recovered from
      patients who had received trimethoprim or ciprofloxacin while the stent was
      indwelling. These stents were examined with X-ray photoelectron spectroscopy
      (XPS) and scanning electron microscopy/energy-dispersive X-ray analysis (SEM/EDX)
      for the presence and composition of encrustation or biofilm. Conditioning films
      and encrustations were found on all stents. Encrustation elements (Ca, Mg, P)
      were identified on 11 of 16 Black Beauty (69%), 7 of 16 LSe (44%), and 12 of 32
      SofFlex (38%) stents. The stent type, duration of insertion, and age or sex of
      the patient did not correlate significantly with the amount of encrustation.
      Bacterial biofilms were found on 1 of 7 Black Beauty stents (14%) and 7 of 32
      SofFlex stents (22%). In a second study, an additional 28 patients with SofFlex
      stents were treated with ciprofloxacin (N = 16) or ofloxacin (N = 12). Their
      stents were subjected to high-performance liquid chromatography to determine if
      oral antibiotic therapy can lead to drug adsorption to the stent. Analysis showed
      that both ciprofloxacin and ofloxacin adsorbed to the stent surfaces. The mean
      concentrations of the two antibiotics within the conditioning film of the stents
      were 0.99 microg/mL and 0.34 microg/mL, respectively. These surface science
      techniques provide a comprehensive method of evaluating ureteral stents and other
      prosthetic devices in vivo.

PMID- 9607435
TI  - Lower-pole caliceal stone clearance after shockwave lithotripsy, percutaneous
      nephrolithotomy, and flexible ureteroscopy: impact of radiographic spatial
      anatomy.
AB  - Spatial anatomy of the lower renal pole, as defined by the infundibulopelvic
      angle (LIP angle), infundibular length (IL), and infundibular width (IW), plays a
      significant role in the stone-free rate after shockwave lithotripsy. A wide LIP
      angle, a short IL, and a broad IW, individually or in combination, favor stone
      clearance, whereas a LIP <70 degrees, an IL >3 cm, or an IW < or =5 mm are
      individually unfavorable. When all three unfavorable factors or an unfavorable
      LIP and IL coexist, the post-SWL stone-free rate falls to 50% or less. Using
      these criteria, more than one fourth of our patients with a lower-pole calculus
      might have been better served by an initial percutaneous or perhaps ureteroscopic
      procedure, neither of which is significantly affected by the lower-pole spatial
      anatomy.

PMID- 9607436
TI  - Stereotactic mechanical percutaneous renal access.
AB  - Obtaining accurate percutaneous renal access when treating intrarenal disease
      requires substantial skill. Robotic devices have been used in a variety of
      surgical applications and have been successful in facilitating percutaneous
      puncture while improving accuracy. Laboratory models of robotic devices for
      percutaneous renal access have also been developed. However, several technical
      hurdles need to be addressed. One relates to the device-patient interface. As a
      first step in creating a complete robotic system, a mechanical arm (PAKY) with
      active translational motion for percutaneous renal access has been developed and
      clinically assessed. The PAKY consists of a passive mechanical arm mounted on the
      operating table and a radiolucent needle driver that uses a novel active
      translational mechanism for needle advancement. The system utilizes real-time
      fluoroscopic images provided by a C-arm to align and monitor active needle
      placement. In vitro experiments to test needle placement accuracy were conducted
      using a porcine kidney suspended in agarose gel. Seven copper balls 3 to 12.5 mm
      diameter were placed in the collecting system as targets, and successful access
      was confirmed by electrical contact with the ball. The PAKY was then used
      clinically in nine patients. The number of attempts, target calix location, calix
      size, and time elapsed were evaluated. In the in vitro study, successful needle
      ball contact occurred the first time in all 70 attempts, including 10 attempts at
      the 3-mm balls. Clinically, percutaneous access to the desired calix was attained
      on the first attempt in each case. The mean target calix diameter was 14.7 mm
      (range 7-40 mm). The mean time elapsed while attempting access was 8.2 minutes.
      No perioperative complications attributable to needle access occurred. Early
      experience indicates that the PAKY provides a steady needle holder and an
      effective and safe end-effector for percutaneous renal access. This device may
      provide the mechanical platform for the development of a complete robotic system
      capable of creating percutaneous renal access.

PMID- 9607437
TI  - Endopyelotomy for high-insertion ureteropelvic junction obstruction.
AB  - We assessed the results of endourologic treatment of patients with a primary
      ureteropelvic junction obstruction (UPJO) caused by high insertion of the ureter
      into the renal pelvis (HIUPJO). A total of 10 patients 15 to 76 years old with
      preoperatively diagnosed HIUPJO were treated. Acucise retrograde endopyelotomy
      was performed in eight patients and percutaneous antegrade endopyelotomy in two.
      A stent was left in place for an average of 5.3 weeks. The subjective success
      rate, based on patient questionnaire and analog pain scales, was 80% at 27
      months' average follow-up. The objective success rate, based on diuretic renal
      scanning or Whitaker test, was 70% at 26 months' mean follow-up. Overall, 60% of
      the patients had both an objectively and a subjectively successful outcome. The
      success rate for endopyelotomy in patients with UPJO caused by high insertion is
      similar to that reported for endopyelotomy in patients without high insertion.
      High insertion is not a contraindication to endopyelotomy.

PMID- 9607438
TI  - Impact of etiology of secondary ureteropelvic junction obstruction on outcome of
      endopyelotomy.
AB  - Endopyelotomy for secondary ureteropelvic junction obstruction (UPJO) is a highly
      effective procedure. However, the impact of the etiology of the obstruction on
      the outcome of an endopyelotomy has not been defined. Herein, we review the
      success rates with endopyelotomy for secondary UPJO after failure of open
      pyeloplasty or endopyelotomy. Thirty-five adult patients with both objective and
      subjective follow-up were identified retrospectively who had endopyelotomy for
      secondary UPJO. Twenty-four patients had failed a previous open reconstruction
      (23) or laparoscopic Foley Y-V plasty (1). Eleven patients had failed a prior
      endopyelotomy. Retrograde endopyelotomy was performed using the Acucise device in
      11 patients, and antegrade endopyelotomy was performed in 24 patients. Objective
      follow-up was obtained with diuretic renal scintigraphy (mean 14.1 months) and
      subjective follow-up by analog pain scales (mean 27.8 months). Objective success
      was defined as no obstruction on renal scintigraphy, while subjective success was
      used to describe a minimum of 50% resolution of symptoms. The subjective success
      rate of secondary endopyelotomy in the open-pyeloplasty group was 88% v 71% in
      the prior endopyelotomy group (P = 0.20). The objective success rate in the
      failed-pyeloplasty group was 71% v 55% in the prior endopyelotomy group (P =
      0.40). Endopyelotomy for secondary UPJO has a good success rate. Success rates
      tend to be higher in patients who have failed an open pyeloplasty; however, a
      statistically significant difference was not seen between the two groups.

PMID- 9607439
TI  - Ureteroscopic evaluation in renal transplant recipients.
AB  - Percutaneous access and antegrade intervention have been the gold standard for
      the management of renal and ureteral complications in the renal transplant
      patient. We reviewed 540 consecutive renal allografts performed between July 1991
      and September 1996 to determine the feasibility and morbidity of diagnostic and
      therapeutic ureteroscopy in renal allograft ureters. Of these, 14 patients (2.5%)
      had indications for endoscopic intervention of the allograft ureter. Four
      patients had obstructive ureteral calculi, three had migrated double-pigtail
      stents, three had persistent suspicious urinary cytology findings necessitating
      diagnostic ureteroscopy, three had persistent funguria, and one had multiple
      ureteral filling defects seen on retrograde ureteropyelography. Ureteropyeloscopy
      was successful in 93% of the patients. A diagnosis was made in all cases,
      including the one unsuccessful ureteroscopy, as this patient had allograft
      ureteral necrosis preventing passage of the endoscope into the renal pelvis. All
      of the migrated stents could be seen, and all but one was retrieved. Two of the
      patients with persistent funguria did have renal fungal balls, which were removed
      endoscopically, and the other case yielded a urothelial biopsy positive for
      fungus. All of the ureteral calculi were removed endoscopically. The only
      complication was ureteral perforation, which occurred in the patient with
      ureteral necrosis. Transplant ureteral endoscopy is a technically challenging
      intervention, but both diagnostic and therapeutic ureteroscopy can be performed
      with acceptable outcomes and minimal morbidity. One should consider ureteroscopy
      as an alternative to percutaneous and antegrade modalities, as these methods
      carry significant morbidity.

PMID- 9607440
TI  - Laparoscopic nephroureterectomy: making management of upper-tract transitional
      cell carcinoma entirely minimally invasive.
AB  - Endoscopic treatment of upper-tract transitional-cell carcinoma (TCC) is well
      established. Nevertheless, many patients still required major ablative surgery.
      We have applied our experience with laparoscopic nephrectomy to the performance
      of laparoscopic nephroureterectomy in order to make the management of upper-tract
      TCC entirely minimally invasive. Since 1993, we have performed 22 laparoscopic
      nephroureterectomies for upper-tract TCC. Initially, we excluded patients with
      tumors below the pelvic brim, but we now offer a trial of laparoscopy to all
      patients. We describe the evolution of our technique, which involves resecting
      the ureteral orifice prior to laparoscopic dissection of the kidney and ureter.
      We have had to convert three cases to open surgery, one each for bleeding,
      failure to progress, and unappreciated tumor extent. Operative times averaged 156
      minutes, which compares well with contemporary times for open nephroureterectomy.
      Complication rates, transfusion requirements, and length of stay, although higher
      than those of laparoscopic nephrectomy, were all reduced in comparison with open
      nephroureterectomy.

PMID- 9607441
TI  - Laparoscopic renal surgery in patients at high risk for intra-abdominal or
      retroperitoneal scarring.
AB  - Prior open abdominal or renal surgery has been considered a relative
      contraindication to laparoscopic surgery because of the likelihood of adhesion
      formation and perinephric scarring, which results in difficulty obtaining access
      to the peritoneal cavity and during surgical dissection. The purpose of this
      study was to examine the feasibility and morbidity of laparoscopic renal surgery
      in patients at high risk for intra-abdominal or retroperitoneal scarring. Twenty
      four patients who underwent laparoscopic renal surgery at our institution gave a
      history of significant open abdominal or renal surgery. Seven patients had
      undergone prior open extraperitoneal (N = 6) or percutaneous (N = 1) renal
      procedures, 10 patients had undergone prior open laparotomy for various reasons,
      and 7 patients had undergone open pelvic surgery. The mean interval from the
      prior operation to laparoscopic renal surgery was 16.5 years (range 0.3-44
      years). Operative time, estimated blood loss, incidence of complications,
      perioperative parenteral narcotic use, length of hospitalization convalescence,
      and degree of intra-abdominal and retroperitoneal scarring were assessed.
      Patients who developed complications were compared with patients who did not. No
      difficulty was encountered while obtaining initial access to the peritoneal
      cavity or retroperitoneal space. No bowel or visceral injuries occurred during
      Veress needle or trocar placement. The laparoscopic procedure was completed
      successfully in all cases. The mean operative time was 4.3 (range 2.0-10.9)
      hours. The mean estimated blood loss was 266 mL (range 50-1200 mL). There were
      eight complications (overall complication 33%) including three major and five
      minor complications. Patients who developed complications had a higher total
      scarring score that those who did not (p = 0.01). For experienced laparoscopic
      surgeons, laparoscopic renal surgery in patients who have a history of open
      abdominal or renal surgery can be successful. Access via the transperitoneal or
      retroperitoneal route can be obtained safely, and the procedure usually can be
      performed in a timely fashion. However, a relatively high perioperative
      complication rate can be expected, particularly for those patients with
      significant intraperitoneal and retroperitoneal scarring.

PMID- 9607442
TI  - Factors involved in gas embolism after laparoscopic injury to inferior vena cava.
AB  - This study evaluated the incidence and factors involved in the occurrence of gas
      embolism after laparoscopic injuries. A 5-MHz transesophageal echocardiographic
      (TEE) probe was placed in 11 anesthetized pigs and used to examine the right
      cardiac chambers and pulmonary artery. A calibrated carbon dioxide analyzer
      continuously measured end-tidal carbon dioxide (ETCO2). The ventilatory settings
      were adjusted to achieve a baseline ETCO2 between 25 and 28 mm Hg. A blinded dose
      response curve for TEE and ETCO2 measurements were created by injecting 0.0007 to
      1.5 mL/kg of CO2 gas intravenously. Venotomies (N = 22) were created
      laparoscopically in the inferior vena cava (IVC) of the study animals. All TEE
      images were videotaped and correlated with laparoscopic events. Embolic episodes
      were classified by comparison with images recorded during the bolus studies. A
      variety of methods for obtaining hemostasis and repairing the venotomies were
      evaluated and their effects on gas embolism were studied. No emboli were noted
      when the venotomies were bleeding freely, the hole was directly occluded, or the
      proximal IVC was compressed. Marked embolism was seen with distal IVC occlusion
      or when there had been significant blood loss. In this situation, manipulation of
      the hole and higher intraperitoneal pressures led to higher degrees of
      embolization. No emboli were seen in an open control group except after
      significant bleeding. The TEE is the most sensitive method of detecting gas
      emboli; however, the majority of episodes are not clinically significant.
      Embolism of CO2 occurs when central venous pressure is decreased by blood loss or
      distal compression. When significant venous bleeding occurs, intravascular volume
      should be maintained and the bleeding site should be directly occluded.

PMID- 9607443
TI  - The laparoscopic cooling sheath: novel device for hypothermic preservation of
      kidney during temporary renal artery occlusion.
AB  - Hypothermia is commonly used to prevent ischemic renal damage during complex
      nephron-sparing surgical procedures requiring temporary renal artery occlusion.
      We developed a novel Cooling Sheath device, which is compatible with laparoscopy,
      to protect the kidney hypothermically during 60 minutes of temporary arterial
      occlusion in a laparoscopic swine model. Comparison of temperature curves and
      histology to control groups undergoing open slush surface cooling and
      laparoscopic warm ischemia for similar time periods was performed. Optimal
      hypothermic temperatures were reached rapidly and maintained with the use of the
      Cooling Sheath. Ischemic damage, present in all kidneys subjected to warm
      ischemia, was not found on histopathologic examination of the cooled kidneys.
      This new device provides hypothermic protection of the kidney during ischemia.
      The use of the Cooling Sheath combined with temporary arterial occlusion will
      allow more complex nephron-sparing renal surgery to be performed using
      laparoscopy.

PMID- 9607444
TI  - Laboratory and clinical assessment of pneumatically driven intracorporeal
      lithotripsy.
AB  - A pneumatically driven intracorporeal lithotripter (the Swiss Lithoclast) has
      recently been approved for use in the United States. We compared its performance
      in vitro with ultrasonic, electrohydraulic and laser lithotripsy devices using a
      standard plaster-of-Paris stone phantom. The probe sizes and output settings were
      identical to those used during clinical treatment. The fragmentation efficiency
      index (measured as the lithotripsy time needed to reduce the stone phantom to
      particles <2 mm divided by the initial stone weight) ranged from 5.0 to 8.5 min/g
      of stone mass, with this value increasing from pneumatic to electrohydraulic to
      laser and to ultrasonic lithotripsy. We also performed an objective study in a
      swine model, which showed no adverse consequence of pneumatic lithotripsy.
      Finally, we evaluated our initial 41 patients who had undergone pneumatic stone
      fragmentation. We treated 8 patients having 11 renal calculi, 30 patients having
      37 ureteral calculi, and 3 patients having 6 bladder calculi employing pneumatic
      probes ranging in size from 0.8 to 2.0 mm. Stone fragmentation was successful in
      a single session in 95% of the ureteral calculi and 100% of both renal and
      bladder calculi. Stone analysis in 23 patients revealed 17 (74%) calcium oxalate
      monohydrate and 1 (4%) cystine calculi. Our clinical and laboratory assessment of
      this newly developed pneumatic lithotripsy device further validates its efficacy
      in fragmenting stone of all compositions and its overall safety associated with
      clinical application.

PMID- 9607445
TI  - Renal osteopontin expression in experimental urolithiasis.
AB  - Although osteopontin (Opn) is a strong inhibitor of calcium oxalate
      crystallization in vitro, its role in stone formation in vivo is unknown. We
      investigated the renal expression of Opn in normal, ethylene glycol (EG), and EG
      + ammonium chloride-treated rats. Male Sprague-Dawley rats were divided into
      three groups. Group 1 (N = 5) was the control. Animals in Group 2 (N = 6)
      received 4 weeks of treatment with 0.75% EG, and Group 3 animals (N = 6) were
      given 1 week of treatment with 0.75% EG and 1.0% NH4Cl. The kidneys were then
      examined for crystal deposition and Opn localization. In normal rats, staining
      for Opn was evident in the proximal tubules (PT; S3 > S2 > S1), distal tubules
      (DT), and the thick ascending limbs of Henle (TAL) and a few collecting ducts
      (CD). All rats in Group 3 had significant crystal deposition throughout their
      kidneys. In Group 2 rats, Opn staining increased in all segments of the PT, DT,
      and TAL. Staining in these tubular segments was even greater in Group 3 rats,
      including the CD and the papillary surface epithelium. In addition, Opn was
      present within all crystal deposits. Renal Opn expression in experimental
      urolithiasis becomes stronger and more diffuse as the severity of the lithiasis
      inducing treatment increases. These results are consistent with the hypothesis
      that renal epithelial cells produce larger amounts of osteopontin to combat the
      development of kidney stones.

PMID- 9607446
TI  - High-speed photographic evaluation of holmium laser.
AB  - Little information has been published regarding the relative contributions and
      exact mechanisms involved in stone fragmentation during holmium laser
      lithotripsy. High-speed photography has been used to evaluate other
      intracorporeal lithotripsy devices, and we chose this method to evaluate the
      holmium laser. High-speed photographic evaluation of cavitation bubbles produced
      by the four fiber sizes (200, 365, 550, and 1000 microm) showed a moderate degree
      of correlation (n = 0.71 for 1 J pulses, r = 0.80 for 4 J pulses) between maximal
      bubble size and fiber diameter. Eliminating the data from the eroded 550 microm
      fiber strengthened the correlation to r = 0.94 for 1 J pulses and r = 0.99 for 4
      J pulses. The importance of keeping fiber tips in good working condition was
      thereby demonstrated. Evidence of a thermal effect of the laser on stone and
      chalk was also obtained. In a parallel study, no correlation (r = -0.08) was
      found between fiber diameter and stone fragmentation efficiency using chalk as an
      in vitro stone model.

PMID- 9607447
TI  - Evaluation of retropulsion caused by holmium:YAG laser with various power
      settings and fibers.
AB  - The ideal intracorporeal lithotriper would comminute all types of calculi into
      small readily excreted particles. It would be small and flexible with an energy
      source safe for the uroepithelium. It should not break, should be inexpensive,
      and should not retropulse the stone up the urinary tract. This investigation was
      designed to quantify the last quality for the holmium:YAG laser. The mechanism of
      action of the pulsed Ho:YAG laser (wavelength 2100 nm) is the generation of a gas
      plasma at the stone-fluid interface causing a shockwave. The holmium laser was
      employed for lithotripsy of model stones composed of silicate with a ferrous
      coating. Stones were selected with a mass of 2 mg +/- 0.1 mg. We sequentially
      investigated three variables: energy (0.6, 0.8, and 1.0 J), frequency (10, 16,
      and 20 Hz), and fiber diameter (200, 365, 550, and 1000 microm). Ten stone trials
      were performed with each of the 36 possible combinations of energy, pulse
      frequency, and fiber diameter. Our model ureter consisted of a clear rigid
      polymer tube filled with 0.9% saline. The system was closed and permitted
      intertrial flushing of generated air bubbles. The laser fiber was maintained at
      constant extension from the ureteroscope, with stones positioned at the fiber tip
      before each trial. Laser energy was applied for 2 seconds, with maximum and net
      retropulsion recorded in millimeters. Each measurement series was recorded in a
      database for paired Student t-tests. Net retropulsion was then compared by
      statistically holding each of the three variables constant (fiber size constant
      with power and frequency varying; frequency constant with power and fiber size
      varying; and power constant with fiber size and frequency varying). Most
      retropulsion occurred with the 365-microm and 550-microm fibers. Most comminution
      was also noted with these fiber sizes. There was no statistical correlation
      between observed retropulsion and efficiency of comminution. This self-contained
      model for laser lithotripsy allowed us to measure retropulsion accurately.
      Silicate stones are not chemically similar to human uroliths but are of uniform
      composition. The irregular surface characteristics are similar to human stones,
      making them ideal for retropulsion investigations.

PMID- 9607448
TI  - Endoscopic subcutaneous neurovascular lower-extremity myofascial flap harvesting
      for genitourinary reconstruction.
AB  - Neurovascular myofascial flaps have been widely utilized when healthy tissues
      outside the anatomic confines of the pelvis are necessary for complex
      genitourinary reconstructions. Myofascial flaps have great potential in providing
      support and tone to the bladder neck in a model of total urinary incontinence.
      Two muscles were evaluated for minimally invasive harvesting utilizing an adult
      rabbit and human cadaveric model: the gracilis, because of its neurovascular
      supply and length, and the sartorius, because of its location. Three adult New
      Zealand White rabbits were prepared and draped in sterile fashion after general
      anesthesia. Bilateral 2-cm incisions were made over the origins of the gracilis
      and sartorius muscles. Dissection times were entered in a database on a personal
      computer for paired Student t-tests. Special techniques for dissection included
      utilization of a 5-mm subcutaneous dissector/retractor and reticulated scissors
      and dissector. Once the tissues were harvested, rotational angles of the
      functional arcs around the origins of the gracilis and sartorius flaps were
      measured, as were the lengths of the muscular flaps from the proximal pedicle to
      the free distal end. Initial positioning of the myofascial flap at the bladder
      neck was investigated in this nonsurvival study. Blood loss was estimated before
      the animals were humanely sacrificed. The possibilities of minimally invasive
      genitourinary reconstruction are numerous. Both flaps can be dissected
      endoscopically and have rotational angles allowing transfer to more cephalad
      positions in the groin or intra-abdominally. Further studies are needed to
      establish the efficacy of the myofascial graft for minimally invasive
      genitourinary reconstructions.

PMID- 9607449
TI  - Increased intra-abdominal pressure during pneumoperitoneum stimulates endothelin
      release in a canine model.
AB  - Prolonged pneumoperitoneum during laparoscopic surgery has been associated with
      oliguria in clinical experimental studies. Although the pathophysiology of this
      oliguria is thought to be renal parenchymal and venous compression, the role of
      the potent vasoconstrictor endothelin (ET) has not been studied. The purpose of
      this study was to investigate the effect of pneumoperitoneum on endothelin
      release and renal function in a canine model. Two groups of dogs were studied
      during pneumoperitoneum (Group 1, N = 7) or isolated left renal vein compression
      (Group 2, N = 6). Urine and plasma samples were collected for urine output,
      glomerular filtration rate (GFR), urine sodium, and plasma endothelin
      measurements. In Group 1, GFR fell significantly (p < 0.05) by 49% from a control
      of 0.88 +/- 0.12 mL/min per gram of kidney weight. Urine volume fell by 79% (p <
      0.05) from a control value of 0.014 +/- 0.003 mL/min/gkw. Sodium excretion was
      decreased by 88%. Sodium reabsorption was significantly enhanced during
      pneumoperitoneum (99.56 +/- 0.15% v 98.44 +/- 0.25%). Arterial plasma ET
      concentrations were elevated by 8% during the first 20 minutes of
      pneumoperitoneum (30.8 +/- 3.6 v 33.3 +/- 3.4 pg/mL; p < 0.05). In Group 2, left
      renal vein compression resulted in a 31% decrease (p < 0.05) in GFR in the left
      kidney and a 25% decrease in the right kidney. Urine volume fell by 67% in the
      left kidney and 40% in the right. Renal venous ET concentrations also increased
      after renal vein compression. Although the mechanism by which oliguria occurs
      during pneumoperitoneum is not fully understood, the ET concentration was
      elevated. Because ET can decrease RBF, GFR, and sodium excretion, it may
      contribute to the oliguria observed during long periods of pneumoperitoneum.

PMID- 9607450
TI  - Initial studies of holmium:YAG laser creation of spinal defects in fetal rabbits:
      model for urologic effects of myelomeningocele.
AB  - Myelomeningocele (MMC) is characterized by paraplegia and incontinence, often
      necessitating surgery. Current models of MMC in sheep and primates create a
      spinal defect long after anomalous neural tube closure ordinarily occurs. An
      ideal model of MMC would allow creation of the defect at the earliest age in a
      low-cost species with a short gestation. We present a method utilizing the
      holmium laser to create spinal defects in rabbits in utero for the study of the
      pathophysiology and repair of MMC. Pregnant rabbits of 22 to 23 days' gestational
      age were prepared and draped in sterile fashion for laparotomy under general
      anesthesia. The abdomen was opened, and both uterine horns were inspected. Double
      opposing pursestring sutures were placed to secure the chorioamniotic membranes
      over the fetal lumbar spine. Amniotic fluid was removed with a needle and saved.
      Electrocautery was used to open the uterus within the pursestring suture,
      exposing the fetal dorsum. The spine was exposed by laser dissection of the fetal
      dorsal musculature. Posterior laminectomy was accomplished with laser incisions
      of each side of the spinous process, leaving the underlying dura and cord
      exposed. The pursestring was then cinched, amniotic fluid was returned, and the
      uterus and trocar sites were closed. Cesarian section was performed at 30 to 31
      gestational days, and the pups were examined and then humanely sacrificed for
      histologic evaluation of the lesion. The rabbit is an inexpensive species with a
      short gestation (33-35 days), and four or more fetuses may be operated on per
      litter, with the remainder serving as controls. Utilization of minimally invasive
      techniques including holmium:YAG laser dissection facilitates creation of spinal
      defects at an early age in this small-animal model.

PMID- 9607451
TI  - Can a hydrophilic guidewire be resterilized?
AB  - The Glidewire (Microvasive, Natick, MA) or Terumo wire (Terumo, Japan) is
      constructed with a hydrophilic polymer surface that enables easier passage
      through narrowed lumens in the urinary tract. This study examined the effects of
      gas sterilization on Glidewire surface structure, slipperiness, and ability to
      support bacterial growth. Light microscopy at 100x and 400x and scanning electron
      microscopy at 100 to 1300x were used to compare the surface tips of five new
      0.038-inch Glidewires with those resterilized one or three times. The tips were
      immersed in water prior to standard gas sterilization for operating room
      equipment. Subjective evaluation of slipperiness involved asking 10 blinded
      urologists to assess the nature of new and resterilized wires by feel. Support of
      bacterial growth was assessed by comparing cultures performed on new wires
      (control) with those of wires incubated with Bacillus stearothermophilus.
      Microscopy, reviewed by a pathologist, revealed no perceivable surface
      differences after one and three gas sterilizations. Eight of the urologists noted
      similar or improved slipperiness of resterilized wires compared with new wires.
      Bacterial cultures of intentionally infected wire segments showed no growth after
      standard gas sterilization in all cases. In this study, gas sterilization did not
      adversely affect the lubricious nature or the surface coating of the hydrophilic
      coating of Glidewires. Also, gas resterilization was bactericidal to new and used
      wires that had been infected with a heat-tolerant organism.

PMID- 9607452
TI  - Organized activation during atrial fibrillation in man: endocardial and
      electrocardiographic manifestations.
AB  - INTRODUCTION: Atrial fibrillation is not entirely random, but little is known
      about the spatiotemporal endocardial organization and its surface ECG
      manifestations. METHODS AND RESULTS: In 16 patients with atrial fibrillation
      (chronic, n = 14), endocardial mapping of the trabeculated, the posteroseptal
      smooth right atrium, and the coronary sinus was performed using multipolar
      catheters. The surface ECG was analyzed by determining "fibrillation wave" (F
      wave) amplitude, rate, and polarity. During 50 minutes of atrial fibrillation, an
      organized activation was present 72% +/- 32% of the analyzed time on the
      trabeculated, 19% +/- 15% on the smooth right atrium (P < 0.01), and 51% +/- 33%
      along the coronary sinus (P < 0.05). The direction of organized activation was
      craniocaudal in 72% +/- 16%, caudocranial in 10% +/- 9% (P < 0.01), and
      indeterminable in 18% +/- 11%. The mean surface F wave amplitude in lead V1 was
      0.128 +/- 0.06 mV during 28 seconds of atrial fibrillation with a craniocaudal
      direction of activation and 0.065 +/- 0.02 mV during a disorganized activation (P
      < 0.01). A stable relation between surface F waves and organized trabeculated
      right atrial activation was observed, and the mean F wave cycle length (190 +/-
      27 msec) was highly comparable to the simultaneously measured endocardial cycle
      length (191 +/- 27 msec, correlation coefficient 0.97). F wave polarity in V1 was
      positive in 12 of 14 patients during craniocaudal and negative in 11 of 14
      patients during caudocranial right atrial free-wall activation. CONCLUSION: An
      organized activation during atrial fibrillation with a predominant craniocaudal
      direction on the trabeculated right atrium is frequently present and influences
      the appearance of "coarse" or "fine" atrial fibrillation as well as F wave
      polarity on the surface ECG.

PMID- 9607454
TI  - Atrioventricular nodal reentry tachycardia in patients with sinus node
      dysfunction: electrophysiologic characteristics, clinical presentation, and
      results of slow pathway ablation.
AB  - INTRODUCTION: Sinus node dysfunction (SND) is frequently associated with impaired
      AV conduction. This study investigated the electrophysiologic properties of dual
      AV nodal pathways in patients suffering from both SND and AV nodal reentrant
      tachycardia (AVNRT). METHODS AND RESULTS: Two groups of patients with slow-fast
      AVNRT underwent invasive electrophysiologic testing and catheter ablation of the
      slow pathway. Group A comprised 10 patients with SND (age 70 +/- 8 years). Group
      B included 10 age-matched patients without SND (age 69 +/- 7 years; P = NS) who
      served as controls. Patients of group A exhibited prolongation of the anterograde
      Wenckebach cycle lengths (WBCLs) of both the fast pathway (559 +/- 96 vs 361 +/-
      38 msec; P < 0.01) and the slow pathway (409 +/- 57 vs 339 +/- 32 ms; P < 0.01).
      However, the delta between the WBCLs of the fast and the slow pathways was larger
      in patients of group A (150 +/- 80 vs 22 +/- 20 msec; P < 0.01). Retrograde fast
      pathway conduction was well preserved with no difference in WBCLs (356 +/- 42 vs
      330 +/- 47 msec; P = NS). Cycle lengths of AVNRT were longer in group A (468 +/-
      46 vs 363 +/- 37 msec; P < 0.01). Clinically, all patients of group A suffered
      from multiple episodes of AVNRT per week, which was not the case in any patient
      of group B (P < 0.01). Catheter ablation of the slow pathway eliminated AVNRT in
      all patients without complications. CONCLUSIONS: Patients with AVNRT and SND
      exhibit characteristic electrophysiologic alterations of both AV nodal pathways.
      Clinically, this results in significantly more frequent episodes of tachycardia.
      Slow pathway ablation appears to be safe and effective in these patients.

PMID- 9607453
TI  - Hybrid pharmacologic and ablative therapy: a novel and effective approach for the
      management of atrial fibrillation.
AB  - INTRODUCTION: Maintenance of sinus rhythm in patients with recurrent atrial
      fibrillation is often difficult to achieve with pharmacologic therapy. Complex
      catheter ablative procedures are being developed, but efficacy and safety issues
      remain to be clarified. We hypothesized that combined pharmacologic and simple
      ablative therapies in a targeted subset of patients will improve success in the
      treatment of atrial fibrillation. METHODS AND RESULTS: We identified 13 patients
      (mean age 61.5 +/- 16.2 years) with atrial fibrillation who converted to
      electrocardiographic atrial flutter during antiarrhythmic drug treatment. Surface
      ECG suggested "typical" atrial flutter in 11 patients and "atypical" atrial
      flutter in 2. Intracardiac mapping and entrainment studies revealed 9 patients
      had counterclockwise isthmus-dependent atrial flutter, and the remaining 4 had
      complex activation patterns, suggesting the presence of multiple wavefronts. All
      9 patients with typical atrial flutter underwent successful ablation. None of the
      4 patients with complex activation patterns had successful ablation. Patients
      were followed for recurrences of atrial arrhythmias via clinic visits, record
      review, and interviews. In patients who underwent successful ablation and
      continued on antiarrhythmic drugs, 88.9% remain in sinus rhythm after a mean
      follow-up of 14.3 +/- 6.9 months (range 1 to 28). CONCLUSION: In patients who
      experience conversion of atrial fibrillation to atrial flutter during
      antiarrhythmic drug treatment, ablation and continuation of pharmacologic therapy
      is a safe and effective means of achieving and maintaining sinus rhythm.

PMID- 9607455
TI  - Can alteration of dual atrioventricular nodal pathway physiology be related to
      sinus node dysfunction?

PMID- 9607456
TI  - Effects of blocked atrial beats on the atrioventricular nodal recovery property:
      facilitation or depression?
AB  - INTRODUCTION: Blocked atrial beats (A(B)) usually have concealed AV nodal
      penetration, which can change the nodal conduction time (AH) of a subsequent
      beat. However, without an output marker it is difficult to assess their effect on
      the node. In this report we used all possible parameters as nodal resting time
      after A(B) and plotted them against the AH of testing beats to study their
      effects on the node. METHODS AND RESULTS: Atrial extrastimulation studies were
      done in 21 patients in whom one blocked atrial beat (A(2B)) was observed. Nodal
      recovery curves were obtained for basic pacing (A1), after a conducted premature
      beat (A2), and after A(2B). In six patients there were 2 to 3 consecutively
      blocked beats (A(nB)) and recovery curves were constructed after each A(nB).
      Nodal recovery curves were plotted with AH of the testing beat against different
      nodal resting parameters and fitted to a single exponential equation. We found
      contradicting phenomena when using different formats. (1) For recovery curves of
      A(2B), there was a rightward shift from that of the basic curve when using H1A3
      or A1A3 as the gauge (depression phenomenon). On the contrary, there was a
      leftward shift of the curves when using A(2B)A3 (facilitating phenomenon). (2)
      For recovery curves after multiple blocked beats there was a marked rightward
      shift of all curves except A(n-1)(B)An-curves, which were all leftward shifted.
      CONCLUSION: Because these contradicting phenomena were dictated by the presenting
      formats, the terms "depression" and "facilitation" cannot be considered intrinsic
      AV nodal properties outside of the strict context of the pacing protocol and the
      format of data presentation.

PMID- 9607457
TI  - Body surface potentials during discharge of the implantable cardioverter
      defibrillator.
AB  - INTRODUCTION: Little is known about the hazard for persons in contact with
      patients experiencing a high-voltage discharge of their implantable cardioverter
      defibrillator (ICD). Compared to epicardial systems, this risk may be increased
      with transvenous electrode systems and particularly in active can configurations.
      METHODS AND RESULTS: In 23 patients with a transvenous active can ICD system,
      body surface potentials Vs and current through an external resistance were
      measured during 35 discharges. Vs was detected using skin electrodes positioned
      over the left subpectorally implanted pulse generator [C], apex of the heart [A],
      and the right pectoral region [RP]. Mean Vs during discharges without an external
      shunt resistance ranged between 13 and 63.8 V [C to A] and 12.5 to 47.3 V [C to
      RP] (ICD peak stored/output voltage Vcap = 183 to 606 V, n = 20). Mean current
      flow [C to A] was 8.2 to 46.8 mA (Vcap = 288 to 633 V, n = 10) and 42 to 120.7 mA
      (Vcap = 447 to 579 V, n = 5) across a resistance of 1,696 and 797 omega,
      respectively. CONCLUSION: During high-output shocks, a considerable potential
      difference is present on the body surface of ICD patients that, according to the
      literature, may induce a single cardiac response in a bystander. Analogous to
      spontaneous extrasystoles, there is only a minimal chance of triggering a
      tachyarrhythmia by this stimulated extra beat. Direct induction of ventricular
      fibrillation is unlikely, since reported fibrillation threshold values are much
      higher than the observed magnitudes of current and voltage.

PMID- 9607458
TI  - Combination of sotalol and quinidine in a canine model of torsades de pointes: no
      increase in the QT-related proarrhythmic action of sotalol.
AB  - INTRODUCTION: Clinical treatment with a combination of Class IA and III
      antiarrhythmic drugs is not recommended, as they both favor bradycardia-dependent
      proarrhythmic events such as torsades de pointes (TdP). However, this theoretical
      additive effect on ventricular repolarization has never been demonstrated and
      could be questioned as other Class I drugs, such as mexiletine, a Class IB drug,
      limit the number of sotalol-induced TdP in dogs with AV block, suggesting the
      possibility of an antagonistic action of Class I properties against Class III
      effects. METHODS AND RESULTS: We compared the electrophysiologic and
      proarrhythmic effects of sotalol (Class III) alone and combined with quinidine
      (Class IA) in a canine model of acquired long QT syndrome. Seven hypokalemic (K+:
      3 +/- 0.1 mEq/L) dogs with chronic AV block had a demand pacemaker implanted and
      set at a rate of 25 beats/min. They were submitted to two (sotalol-alone and
      sotalol-plus-quinidine) experiments 48 hours apart using a randomized cross-over
      protocol. They were pretreated with quinidine (10 mg/kg + 1.8 mg/kg per hour) or
      saline infused throughout the experiment, and given sotalol (4.5 mg/kg + 1.5
      mg/kg per hour) for 2 hours, 30 minutes after the beginning of the pretreatment
      infusion during both experiments. Ventricular and atrial cycle lengths were
      similarly increased by sotalol after quinidine or saline. The sotalol-induced
      prolongation of the QT interval was significantly shorter in quinidine-pretreated
      dogs (24 +/- 7 msec after quinidine vs 40 +/- 8 msec after saline). Fewer dogs
      developed TdP: significantly during the first hour of infusion (1/7 sotalol-plus
      quinidine vs 6/7 sotalol-alone dogs, P < 0.05) but nonsignificantly during the
      second hour (3/7 vs 6/7). CONCLUSION: In this model, the sotalol-plus-quinidine
      combination is at least no more arrhythmogenic than either of the drugs given
      alone.

PMID- 9607459
TI  - Dynamic changes of 12-lead electrocardiograms in a patient with Brugada syndrome.
AB  - We present a patient with Brugada syndrome in whom 12-lead ECGs were recorded
      just before and after an episode of ventricular fibrillation (VF). A progressive
      elevation of both the RS-T segment and J waves just preceding and following the
      VF, and a close relationship between the amplitude of the RS-T segment and the
      preceding R-R intervals during atrial fibrillation, were documented. These
      findings support the hypothesis that RS-T elevation and a subsequent VF are
      related to a transient outward current-mediated spike-and-dome morphology of the
      epicardial action potential.

PMID- 9607460
TI  - The Brugada syndrome.

PMID- 9607461
TI  - Ventricular tachycardia: a life-threatening arrhythmia in a patient with
      congenitally corrected transposition of the great arteries.
AB  - Ventricular tachycardia (VT) is an uncommon finding in patients with congenitally
      corrected transposition of the great arteries (CCTGA). Cardiac death in patients
      with CCTGA has been attributed to complete heart block, systemic ventricular
      dysfunction, or severe AV valve regurgitation with heart failure. We describe the
      case of a patient who presented with palpitations and near-syncope that was
      associated with clinical episodes of VT. Programmed ventricular stimulation
      revealed easily inducible sustained VT that immediately degenerated to
      ventricular fibrillation and subsequently required therapy with an implantable
      cardioverter defibrillator.

PMID- 9607462
TI  - Catheter ablation of accessory atrioventricular connection between right atrial
      appendage to right ventricle: a case report.
AB  - A 24-year-old woman had experienced frequent attacks of orthodromic AV
      reciprocating tachycardia. The polarity of the delta waves suggested a right
      anterior or anterolateral accessory pathway. After ablation at the tricuspid
      annulus was unsuccessful, earliest retrograde atrial activation was recorded on
      the floor of the right atrial appendage, 2 cm above the tricuspid ring.
      Application of radiofrequency energy at this site abolished accessory pathway
      conduction. This unusual accessory pathway, located between the floor of the
      right atrial appendage and the right ventricle, was amenable to radiofrequency
      catheter ablation from within the right atrial appendage.

PMID- 9607463
TI  - Progressive depolarization: a unified hypothesis for defibrillation and
      fibrillation induction by shocks.
AB  - Experimental studies of defibrillation have burgeoned since the introduction of
      the upper limit of vulnerability (ULV) hypothesis for defibrillation. Much of
      this progress is due to the valuable work carried out in pursuit of this
      hypothesis. The ULV hypothesis presented a unified electrophysiologic scheme for
      linking the processes of defibrillation and shock-induced fibrillation. In
      addition to its scientific ramifications, this work also raised the possibility
      of simpler and safer means for clinical defibrillation threshold testing. Recent
      results from an optical mapping study of defibrillation suggest, however, that
      the experimental data supporting the ULV hypothesis could instead be interpreted
      in a manner consistent with traditional views of defibrillation such as the
      critical mass hypothesis. This review will describe the evidence calling for such
      a reinterpretation. In one regard the ULV hypothesis superseded the critical mass
      hypothesis by linking the defibrillation and shock-induced fibrillation
      processes. Therefore, this review also will discuss the rationale for developing
      a new defibrillation hypothesis. This new hypothesis, progressive depolarization,
      uses traditional defibrillation concepts to cover the same ground as the ULV
      hypothesis in mechanistically unifying defibrillation and shock-induced
      fibrillation. It does so in a manner consistent with experimental data supporting
      the ULV hypothesis but which also takes advantage of what has been learned from
      optical studies of defibrillation. This review will briefly describe how this new
      hypothesis relates to other contemporary viewpoints and related experimental
      results.

PMID- 9607464
TI  - Current concepts of ventricular defibrillation.
AB  - The aim of this article is to review the current concepts of ventricular
      defibrillation. We studied the interaction between strong electrical stimulus and
      cardiac responses in both animal models and in humans. We found that a premature
      stimulus (S2) of appropriate strength results in figure-eight reentry in vitro by
      inducing propagated graded responses. The same stimulation protocol induces
      figure-eight reentry and ventricular fibrillation (VF) in vivo. When the S2
      strength and the magnitude of graded responses increase beyond a critical level,
      the increase in refractoriness at the site of the stimulus becomes so long that
      the unidirectional block becomes bidirectional block, preventing the formation of
      reentry (upper limit of vulnerability [ULV]). In other studies, we found that the
      effects of an electrical stimulation on reentry is in part determined by the
      timing of the stimulus. A protective zone is present after the induction of VF
      and after an unsuccessful defibrillation shock during which an electrical
      stimulus can terminate reentry and protect the heart from VF. These results
      indicate that the effects of a defibrillation shock is dependent on both the
      strength and the timing of the shock. Timing is not important in areas where the
      shock field strength is > or = ULV because the shock terminates all reentry but
      cannot reinitiate new ones. However, in areas where shock field strength is <
      ULV, the effects of the shock are determined by the timing of the shock relative
      to local VF activations. This ULV hypothesis of defibrillation explains the
      probabilistic nature of ventricular defibrillation. It also indicates that, to
      achieve a high probability of successful defibrillation, a shock must result in a
      shock field strength of > or = ULV throughout the ventricles.

PMID- 9607465
TI  - Arrhythmia of the month. Explain the pauses.

PMID- 9607466
TI  - Eighteen years' experience with neonatal Hirschsprung's disease treated by
      endorectal pull-through without colostomy.
AB  - METHODS: In the past 18 years, the authors have treated 84 patients with
      Hirschsprung's disease. Of these, 43 patients were under 1 month of age and
      underwent endorectal pull-through without colostomy. Some have undergone follow
      up for as long as 18 years. RESULTS: Thirty-four of these 43 (79%) newborn
      patients were available for follow-up. Twenty-two were totally continent. The
      remaining 12 have normal sphincter tone. Of the 41 patients above 1 month of age,
      34 (83%) were available for follow-up. Some have undergone follow-up for as long
      as 18 years. CONCLUSION: Twenty-two of this latter group (79%) have normal bowel
      control.

PMID- 9607467
TI  - The role of ultrasonography in the diagnosis of pyloric stenosis: a decision
      analysis.
AB  - BACKGROUND/PURPOSE: The appropriate role for ultrasonography (US) as a
      replacement for the upper gastrointestinal series (UGI) in vomiting infants
      remains undefined. The authors have used decision analysis techniques to
      determine whether the use of ultrasonography as an initial screen in vomiting
      infants is cost effective when compared with the UGI as the only study. METHODS:
      Two diagnostic strategies were compared: 1) UGI alone and 2) ultrasonography
      followed by an UGI series in 50% of cases when ultrasonography scan was negative
      for pyloric stenosis. The test sensitivity (US, 0.9; UGI, 1.0) and test
      specificity (US, 1.0; UGI, 1.0) and the incidence of pyloric stenosis among
      vomiting infants presenting to the community pediatrician (0.30) or after a
      negative examination by an experienced examiner (0.02 to 0.18) were obtained from
      a review of the literature. The relative charges for ultrasonography and UGI were
      obtained from a national survey from which the cost ratio of US to UGI was
      estimated to range from 0.67 to 1.81 with a median of 1.06. RESULTS: Under these
      baseline assumptions, UGI only was the preferred strategy. The results of the
      decision analysis were sensitive to, or dependent on, assumptions made regarding
      the incidence of pyloric stenosis, the US to UGI cost ratio, the sensitivity of
      the US, and the proportion of patients that proceed to UGI when the US scan was
      negative for pyloric stenosis. When at least 50% of patients whose US scan was
      negative for pyloric stenosis proceeded to a UGI, UGI remained the preferred
      strategy for all cost ratios examined (0.6 to 1.7). Even when no patients
      proceeded to UGI, the cost ratio of US to UGI had to be less than 0.7 under the
      typical incidence (0.30) of pyloric stenosis among vomiting infants presenting to
      the community pediatrician for US to be cost effective. Finally, only UGI was
      indicated when an olive was not appreciated by an experienced examiner.
      CONCLUSION: Under assumptions that fit most clinically relevant circumstances,
      the UGI as the initial study is the most cost-effective radiological diagnostic
      test in the evaluation of the vomiting infant.

PMID- 9607468
TI  - A quantitative study of the morphological and histochemical changes within the
      nerves and muscle in infantile hypertrophic pyloric stenosis.
AB  - PURPOSE: The aim of this study was to quantify changes in dimensions of nerves
      and muscle and the proportionate expression of neural antigens in infantile
      hypertrophic pyloric stenosis (IHPS). METHODS: Twenty specimens of pylorus from
      children with IHPS and age/sex-matched controls were examined using conventional
      histology and immunohistochemistry for a range of nerve and muscle antigens. The
      changes in the proportion of nerves expressing each antigen were quantified and
      statistically analyzed. RESULTS: The longitudinal muscle was found to be
      hypertrophic and protein gene product 9.5-stained nerves appeared longer and
      thicker in the myenteric plexus and shorter in the longitudinal muscle layer in
      IHPS. The proportion of nerves that expressed neural nitric oxide synthase (nNOS)
      was found to be diminished in all the IHPS tissues examined. In the circular
      muscle and myenteric plexus, the proportion of nerves that expressed vasoactive
      intestinal polypeptide (VIP) and nNOS was almost identically diminished. The
      expression of calcitonin gene-related polypeptide and substance P was
      proportionately reduced in the myenteric plexus. CONCLUSIONS: The results of this
      study represent the first quantitative analysis of nerves and muscle in IHPS. The
      muscle hypertrophy is not restricted to circular muscle layer. The changes in
      nerve morphology cannot be attributed to a dilutional effect of the muscle
      hypertrophy. The selective changes in nerve and ganglion morphology varies
      between tissue layers and neural antigen expressed. The findings of reduced
      proportions of nerves expressing, in particular, nNOS may shed some light on the
      etiology of this condition.

PMID- 9607469
TI  - Indomethacin-induced reduction in neonatal piglet mesenteric blood flow is
      blunted by dopexamine.
AB  - BACKGROUND: Dopexamine is a specific dopaminergic and beta2-adrenergic agonist.
      Using newborn piglets, we have previously shown that (1) dopexamine increases
      cardiac output and mesenteric blood flow; (2) indomethacin reduces mesenteric
      blood flow. METHODS: Ultrasonic blood flow probes were placed around the
      ascending aorta, cranial mesenteric artery, and a renal artery of 0 to 2-day-old
      and 2-week-old piglets. Animals of each age were grouped (5 to 8 animals per
      group) and subjected to one of three experimental protocols: (1) 0.4 mg/kg
      indomethacin infusion, (2) 10 microg/kg/min dopexamine infusion begun 10 minutes
      before indomethacin, or (3) no treatment. RESULTS: Control animals demonstrated
      no significant alterations in mesenteric blood flow. Compared with baseline,
      indomethacin produced significant (P< .05, analysis of variance) declines in
      cranial mesenteric artery blood flow in 0 to 2-day old (37.2+/-5.7 mL/min v
      17.9+/-3.7 mL/min at 90 min), and 2-week-old (80.2+/-12.5 mL/min v 29.7+/-5.7
      mL/min at 90 minutes) piglets. In both animal groups treated with dopexamine
      before indomethacin, the decreases in cranial mesenteric artery blood flow were
      eliminated (38.4+/-7.6 mL/min at baseline v 36.5+/-6.8 mL/min at 90 minutes in 0
      to 2 day olds; 79.9+/-10.0 mL/min at baseline v 77.5+/-14.7 mL/min in 2 week
      olds). Indomethacin-induced declines in renal blood flow were similarly abrogated
      by dopexamine. CONCLUSION: Dopexamine may prove of clinical benefit when a
      neonate is considered a candidate for indomethacin therapy.

PMID- 9607470
TI  - Long-term total parenteral nutrition-induced hepatobiliary dysfunction in a
      rabbit model.
AB  - BACKGROUND/PURPOSE: Currently, the reason for hepatobiliary dysfunction
      associated with long-term total parenteral nutrition (TPN) is much debated and
      still unclear. No agreement can be achieved about whether bacteriotoxins and
      sepsis, enteral starvation, consequences of abdominal operations, or the TPN
      solution itself is the real cause for the disease. Animal models were criticized
      for their short period of TPN and their failure to demonstrate cholestasis and
      bile duct proliferation. The aim of this study was to establish an animal model
      for long-term TPN in which the same alterations of the hepatobiliary system as
      observed in humans could be produced. METHODS: In this model, rabbits could be
      kept for the first time under continuous TPN for 4 weeks. Three serial liver
      biopsy sections were taken operatively from each animal and biochemical analyses
      were performed four times. A control group of enterally fed rabbits underwent
      exactly the same procedure in respect to operations and handling, so that
      differences in macroscopical, biochemical, and histological changes between both
      groups could be attributed exclusively to TPN. RESULTS: Only in the TPN group
      gallbladder distension developed in all animals after 1 week. After 3 and 4
      weeks, viscous dark bile, sludge and stones, a slight rise in direct bilirubin,
      and a decline in plasma albumin and alkaline phosphatase was noted. In both
      groups liver biopsy results showed a similar degree of mild portal inflammation
      and single-cell necrosis at equivalent time points. These changes could be caused
      by antiseptics, antibiotics, anesthesia, and operations. Although mild to
      moderate proliferative changes and no hydropic degeneration developed in the
      control group during the same time, the TPN group generated marked proliferative
      and degenerative changes. We noted as early as 1 week after starting TPN a severe
      hydropic degeneration in 90% of the animals. Fibrosis and bile duct proliferation
      increased from a slight degree after 1 week up to a moderate to severe degree
      after 3 and 4 weeks, respectively. CONCLUSIONS: The hepatobiliary alterations
      associated with TPN in children, which cannot be separated clinically from
      consequences of multiple other factors, can almost identically be reproduced in
      our rabbit model as a clear consequence of TPN. Furthermore, the hydropic
      degeneration of the liver cells begins in zone 3 and is an early predominant
      feature of hepatobiliary dysfunction in rabbits and infants. It must be rated as
      a response to a direct cytotoxic effect on the liver cell.

PMID- 9607471
TI  - Antenatal diagnosis of congenital anomalies of the biliary tract.
AB  - BACKGROUND: The accuracy of the technique of antenatal ultrasonography in the
      diagnosis of congenital bile duct lesions is unknown. METHODS: Thirteen patients
      with proven biliary disease who had abnormal antenatal scans were reviewed. Two
      infants had type I cystic biliary atresia and one had a noncommunicating
      segmental dilatation of the bile duct in a type 3 biliary atresia. The remainder
      had choledochal cysts and included two patients with intrahepatic cysts. The
      correct diagnosis was made antenatally in only two (15%) cases. Of the remaining
      patients, seven received a diagnosis of intraabdominal cysts of unknown etiology,
      three of duodenal atresia, and one ovarian cyst. The median gestational age at
      the antenatal diagnosis was 20 weeks. RESULTS: Jaundice developed in 11 infants,
      and dilatation of intrahepatic biliary radicals was noted in four of the
      choledochal cysts. Obstructive jaundice and increasing cyst size were indications
      for early surgery, and twelve infants underwent a laparotomy at a median age of 4
      weeks. During the median follow-up period of 2 years, 12 of the 13 patients have
      lost their jaundice or remained anicteric. Antenatal diagnosis offers the
      possibility of early definitive surgery for uncomplicated choledochal dilatation
      and the chance of improved outcome for surgically treated biliary atresia. An
      algorithm is suggested for the management of antenatally detected cystic biliary
      lesions.

PMID- 9607472
TI  - Necrotizing enterocolitis after gastroschisis repair: a preventable complication?
AB  - BACKGROUND: Necrotizing enterocolitis (NEC) has been documented in up to 20% of
      infants after repair of gastroschisis and is responsible for significant
      morbidity. NEC is reported to occur up to 10 times more in preterm infants
      receiving standard formula compared with those who have been fed exclusively with
      breast milk. Does breast milk confer a similar protection against NEC in infants
      who have undergone surgery for gastroschisis? METHODS: All newborns with
      gastroschisis delivered between 1990 and 1996 and treated in a single neonatal
      unit were analyzed retrospectively. Clinical data, details of feeding regimens,
      and episodes of definite NEC were recorded. RESULTS: Of 60 infants with
      gastroschisis, 6 (10%) died but none had evidence of NEC. Of the remaining 54
      infants, clinical and radiological signs of NEC developed in 8 (15%). All
      recovered with medical treatment including the three patients with recurrent
      episodes. NEC developed in none of the 12 babies exclusively fed with expressed
      breast milk (EBM) in contrast to 1 (5%) of the 19 who received both EBM and
      formula, and 7 (30%) of the 23 who were fed solely on formula. There was no
      significant difference in gestation, incidence of primary versus silo closure, or
      incidence of intestinal atresia/stenosis in those with NEC (n=8) compared with
      those without (n=46), but birth weight in the NEC group was lower. NEC was less
      likely to develop in infants who received EBM than those who were exclusively
      formula fed (P < .02). CONCLUSION: After gastroschisis repair, feeding with
      maternal expressed breast milk may help to protect the infant from developing
      NEC.

PMID- 9607473
TI  - Thoracoscopy for empyema in children.
AB  - METHODS: During a 19-month period, seven children with empyema underwent
      thoracoscopy. The average age was 7.5 years (range, 3 to 15 years) and the
      duration of illness before surgery 16.5 days (range, 7 to 42 days). All patients
      received preoperative antibiotics, underwent ultrasound or CT scan and
      thoracentesis. Two patients had preoperative intercostal tube drainage.
      Indications for operations were lack of response to antibiotics of loculation of
      pleural fluid on imaging. All procedures were performed under general anesthesia
      with a single lumen tube. RESULTS: Thoracoscopy allowed for good access and
      complete clearance in two patients. In the remaining patients, thoracoscopy
      failed to clear the disease because of difficulty with access, instrumentation,
      and clearance of thick debris. These patients underwent thoracotomy with two
      requiring decortication. CONCLUSIONS: This experience suggests that even in the
      early stage of empyema formation, thoracoscopy is not as effective as
      thoracotomy. Larger experience and studies are required to define the place of
      thoracoscopy in the management of childhood empyema.

PMID- 9607474
TI  - Perianal abscess and fistula-in-ano in infants.
AB  - PURPOSE: The aim of this study was to obtain insight into the short- and long
      term results of treatment of perianal abscess and fistula-in-ano in infants.
      METHODS: This is a retrospective study of the records of patients treated over a
      21-year period from January 1974 until December 1994 in a Pediatric Surgical
      Center. A long-term (1 to 24 year, mean 7.74 year) follow-up by questionnaire
      (response 81%) is also included. RESULTS: Drainage of a perianal abscess is
      followed in 35% of cases by a fistula. Fistulotomy or fistulectomy is followed in
      13% of cases by a recurrence. There were two long-term recurrences that both
      healed spontaneously. The persisting scar sometimes gives problems with anal
      cleaning. All children aged 3 years and older were continent for feces. In two,
      there was soiling for some time. One had constipation and one was incontinent
      during the night. CONCLUSIONS: Simple drainage of a perianal abscess is followed
      frequently by a fistula. Fistulotomy or fistulectomy of a fistula-in-ano in
      infants has a reasonable chance of recurrence in the short term. Long-term
      recurrences are exceptional. There are no serious disabilities in the long run.

PMID- 9607475
TI  - A prospective randomized trial of urokinase as an adjuvant in the treatment of
      proven Hickman catheter sepsis.
AB  - BACKGROUND/PURPOSE: Chronic vascular access catheters have become an important
      adjunct to the treatment of children with complex medical diseases, particularly
      malignancy. One of the major complications of chronic venous access devices is
      bacterial infection of the catheter site and bloodstream. Infusion of systemic
      antibiotics directly into the catheter has been the standard initial therapy with
      failure leading to catheter removal and replacement. It has been suggested by a
      number of investigators that the addition of urokinase as a thrombolytic agent to
      lyse any accumulated thrombus or fibrin would increase the successful catheter
      clearance by antibiotics. This study was designed as a prospective, randomized
      trial to compare treatment of children with positive catheter blood cultures with
      either antibiotics alone or in combination with urokinase 5,000 U boluses 12 and
      24 hours after study entry. METHODS: A total of 63 patients were entered in the
      study. Thirty-three received antibiotics and urokinase, and 30 received
      antibiotics alone. RESULTS: A total of 45 catheters (71%) were cleared of
      infection and salvaged. Treatment failures leading to catheter removal occurred
      in 9 of 33 in the experimental group and 9 of 30 in the control population (no
      significant difference). CONCLUSIONS: Urokinase could not be shown to act as an
      adjuvant in the clearance of infection from chronic central venous access
      catheters that had no evidence of clot or thrombus. This study required the
      performance of a dye study and excluded any patient with a known thrombus. This
      conclusion must therefore be limited to patients with no evidence of a clot or
      fibrin sheath.

PMID- 9607476
TI  - The pathological evaluation of the pediatric inguinal hernia sac.
AB  - BACKGROUND: The College of American Pathologists has suggested that institutions
      should establish guidelines for the evaluation of the hernia sac. In addition,
      some states require the submission of this tissue for pathological evaluation.
      Yet, neither evidence-based guidelines nor published reviews for the evaluation
      of the pediatric hernia sac are available. Therefore, this retrospective study
      was conducted to document experience with the evaluation of the pediatric hernia
      sac. METHODS: All reports of the evaluation of hernia sacs submitted to the
      Department of Pathology during an 8-year period were reviewed. The case of any
      report that differed in any way from "consistent with hernia sac" was evaluated
      for the effect of the findings on the clinical course. RESULTS: A total of 7,924
      hernia sacs were submitted on 6,034 patients. Microscopic evaluation was
      performed on 534. A total of 7,567 (95.4%) submitted specimens on 5,743 patients
      were "consistent with hernia sac" and demonstrated no other findings. Three
      hundred fifty-seven specimens contained findings in addition to hernia sac. In no
      patient did the results of the evaluation have an effect on the patient care.
      CONCLUSIONS: There is strong evidence that the routine pathological evaluation of
      pediatric hernia sacs offers little relevant clinical information. Mandatory
      tissue submission of hernia sacs should be reconsidered.

PMID- 9607477
TI  - The association of large ovarian cysts with cloacal exstrophy.
AB  - BACKGROUND/PURPOSE: Cloacal exstrophy can now be managed with excellent survival
      rates and reasonable long-term outcomes with many of these patients living into
      their late teens and early adulthood. In this report, the authors describe for
      the first time the association of large ovarian cysts with cloacal exstrophy.
      METHODS: From 1974 to 1996, 12 patients with cloacal exstrophy have been treated
      at C.S. Mott Children's Hospital. Massive ovarian cysts developed in four of
      these. These patients represent the subjects of this study. RESULTS: All four
      patients have been followed up beyond puberty and massive ovarian cysts have
      developed, which have caused significant morbidity. Three patients have required
      surgical intervention. All the patients had reached menarche before the
      development of the cysts. In all cases, the presentation was severe pelvic pain.
      Urinary tract obstruction from the large pelvic cysts developed in three of the
      four. The cysts were bilateral in three of four patients and measured 8 to 10 cm
      in diameter on ultrasound scan or computed tomography (CT). Cyst aspiration was
      attempted in two cases and was unsuccessful. Three of the four patients have
      required bilateral salpingo-oophorectomy. The indications for surgery were
      uncontrollable pelvic pain in one and urinary obstruction and uncontrollable
      pelvic pain in two. Surgical findings demonstrated massive thin-walled cysts with
      essentially no normal ovarian tissue in association with duplicated mullerian
      structures. The pathology findings were corpus luteal cyst in two and mucinous
      cystadenoma in one. The fourth patient with an 8- x 10-cm unilateral cyst is
      being followed up. CONCLUSIONS: The authors have described, for the first time,
      the association of massive ovarian cysts with cloacal exstrophy. These cysts can
      lead to severe pelvic pain and urinary tract obstruction. Bilateral oophorectomy
      has been required in most of these patients.

PMID- 9607478
TI  - Congenital aural sinuses: clinical study and application of microsurgery.
AB  - METHODS: The authors studied 45 cases of congenital aural sinuses. RESULTS: Aural
      sinuses were observed on both sides in 17 cases (37.8%) and in girls (24 cases,
      53.3%). Family history was positive in 12 cases (26.6%), and history of local
      infection was present in 40 cases (88.9%). The opening of aural sinuses was
      located most frequently in the marginal helicine region (36 cases, 80%).
      CONCLUSIONS: Microsurgery was extremely effective for accurate determination of
      the margins of intricately ramified aural sinuses, their detachment from
      surrounding tissues, and their total resection. Complete resolution without
      postoperative complications was achieved in 43 cases (95.6%).

PMID- 9607479
TI  - Thyroglossal duct remnant penetrating the hyoid bone--a case report.
AB  - Examination of the thyroglossal duct (TGD) in a senile patient with a
      thyroglossal duct cyst (TGDC), as well as in children, is very valuable in
      understanding the pathology of TGDC. The precise anatomy of TGDC was studied in a
      specimen obtained from a 59-year-old man using three-dimensional reconstruction.
      The authors found the TGD penetrated the hyoid bone. This pathological evidence
      has not previously appeared in the literature. Penetration of the hyoid bone by
      the TGD is the result of a forward growth of the hyoid bone after development of
      a TGD, which had appeared ventral to the hyoid bone. In this gradual forward
      growth, the hyoid bone had first started to press against, before eventually
      engulfing, the TGD.

PMID- 9607480
TI  - Chest wall hamartoma: an alarming chest lesion with a benign course.
AB  - Chest wall hamartoma is a very rare mass lesion of the chest wall that is
      manifest at birth or in early infancy with deformity of the thoracic wall and/or
      varying grades of respiratory distress. The authors report on an 11-month-old
      infant presenting with chest wall hamartoma who was treated by en bloc excision
      of the lesion including the involved ribs. They emphasize the importance of early
      and complete excision of the lesion even in minimally symptomatic patients to
      avoid lethal respiratory complications, more severe postoperative orthopedic
      problems, and malignant transformation.

PMID- 9607481
TI  - Pediatric bronchioloalveolar carcinoma: a favorable pediatric malignancy?
AB  - Primary pulmonary tumors are infrequent in children. Bronchioloalveolar carcinoma
      has been documented rarely in the pediatric population. Before this report, there
      have been only three cases of bronchioloalveolar carcinoma in patients less than
      16 years of age. Our two cases represent two of the youngest cases (ages 6 and 15
      years) reported with bronchioloalveolar carcinoma. They illustrate many of the
      typical findings of this disease including clinical presentation, diagnostic
      difficulty, and better prognosis compared with other pulmonary malignancies. This
      neoplasm appears to have a favorable outcome in childhood.

PMID- 9607482
TI  - Lung volume histograms after computed tomography of the chest with three
      dimensional imaging as a method to substantiate successful surgical expansion of
      the rib cage in achondroplasia.
AB  - The authors describe a radiographic method to quantify a surgical procedure of
      thoracic expansion in a 2-year-old patient with achondroplasia, small chest cage,
      and severe restrictive lung disease. The patient had undergone three surgical
      procedures of thoracic expansion since birth. The authors utilized computer
      generated lung volume histograms after spiral computed tomographic scanning and
      three-dimensional imaging of the lungs to calculate his lung volumes before and
      after the third surgical thoracic expansion. The lung volumes, calculated by the
      histograms, were 363 mL and 406 mL before and after surgery, respectively. This
      40-mL difference in the patient's lung volumes (4 mL/kg) accounted for a
      significant clinical improvement. Lung volume histograms obtained by this
      radiographic method are very helpful in substantiating a successful surgical
      chest expansion or provide an explanation for an unsuccessful repair.

PMID- 9607483
TI  - Acquired umbilical fistula after repair of inguinal hernia: a case report.
AB  - A 2-year, 9-month-old boy had an umbilical fistula after repair of an inguinal
      hernia at 8 months of age. Fistulography findings showed a duct running from the
      umbilicus toward the inguinal wound. Pathological finding of the surgically
      removed fistula demonstrated granulomatous tissues containing silk ligature.
      Acquired umbilical fistula is a rare complication of inguinal herniorrhaphy. Its
      clinical details as well as a review of the previously reported four cases are
      presented.

PMID- 9607484
TI  - Emphysematous pyelonephritis and cystitis associated with bilateral pelviureteric
      junction obstruction: a case report.
AB  - Emphysematous pyelonephritis and cystitis are both rare entities that have not
      been reported in children. The authors report an unusual case of a baby boy
      presenting with bilateral emphysematous pyelonephritis and cystitis associated
      with bilateral pelviureteric junction obstruction and urinary tract infection.

PMID- 9607485
TI  - Fibrosis of the omohyoid muscle--an unusual cause of torticollis.
AB  - An 11-year-old boy had a left neck mass with torticollis. On exploration, a
      fibrotic mass in the superior belly of the left omohyoid muscle was found, which
      shortened the muscle and pulled the hyoid bone downward. Resection of the
      fibrotic muscle was performed. The patient recovered well after the operation
      with resolution of his torticollis.

PMID- 9607486
TI  - Congenital aorto-caval fistula in the newborn: a case report.
AB  - The authors report a rare case of congenital fistula between the distal aspect of
      the descending aorta and the inferior vena cava. The clinical features of this
      aortocaval fistula is being described as well as the preoperative diagnostic
      workup, the intraoperative findings, and the complicated postoperative course and
      treatment.

PMID- 9607487
TI  - Thyroglossal duct cyst with papillary carcinoma in an 11-year-old girl.
AB  - A case of primary papillary carcinoma arising in a thyroglossal duct cyst is
      reported in a young girl. This is a rare finding, with only five pediatric cases
      in the total of 115 cases reported in the literature. Subsequent management is
      described, including the role of scintigraphy and radioiodine ablation.

PMID- 9607488
TI  - Regression of childhood Barrett's esophageal mucosa by antireflux surgery and
      bipolar electrocoagulation.
AB  - The authors report a case of a 13-year-old girl with Barrett's esophagus who
      underwent antireflux surgery and was subsequently treated with endoscopic thermal
      coagulation using bipolar electrocoagulation. Follow-up endoscopy 15 months after
      completion of the endoscopic therapy showed normal esophageal mucosa without
      intestinal metaplasia. Longer follow-up is needed to assess the long-term effects
      of endoscopic treatment of the Barrett's mucosa with thermal coagulation, and
      this procedure should still be considered under investigation.

PMID- 9607489
TI  - Separation of omphalopagus twins: unique reconstruction using syngeneic
      cryopreserved tissue.
AB  - Omphalopagus twin girls were admitted for evaluation of possible separation and
      repair at age 7 days. Prenatal sonographic diagnosis occurred late in the third
      trimester and was followed by cesarean section delivery shortly thereafter.
      Results of extensive evaluation over the next 7 days including x-rays, computed
      tomography and ultrasound scan of the head and torso, and cardiac catheterization
      showed: the gastrointestinal tracts were separate and normal, the livers were
      joined but had separate biliary and vascular systems, and the hearts were
      separate with vastly different anatomy and function. One twin (twin A) had a
      normal heart with a small insignificant VSD. Twin B had a single ventricle, an
      incompetent A-V valve, stenotic pulmonic valve, ASD, PDA, and congenital heart
      block. Hemodynamic support of twin B was almost entirely from twin A. The
      vascular communications between the two consisted of a major connection between
      the internal mammary arteries and large arterial and venous connections
      traversing the joined livers. Because of continued deterioration of twin B,
      separation was undertaken at age 15 days. The separation included dividing the
      liver and the multiple large vascular connections. Two teams then reconstructed
      each twin separately. Twin B began showing signs of cardiac decompensation
      shortly after separation in spite of placement of a pacemaker, pulmonary artery
      banding, and ligation of the PDA. Cardiac function rapidly deteriorated and she
      died. Tissue from her chest wall was cryopreserved and placed in the tissue bank.
      Twin A underwent closure of her abdomen, and received a temporary bovine
      pericardial patch over the chest defect. She subsequently underwent placement of
      a graft of twin B's rib cage to bridge the bony chest defect and skin flap
      closure. She is presently taking a normal diet and thriving at home at age 18
      months. The use of cryopreserved tissue from a syngeneic source provides a unique
      method of reconstruction in this situation.

PMID- 9607490
TI  - Intraoperative localization of small intestinal bleeding in an infant by
      methylene blue injection: a case report.
AB  - During the evaluation of patients with profuse gastrointestinal bleeding, it is
      often difficult to accurately localize bleeding sites in the small intestine.
      Moreover, during laparotomy, there may be no intraoperative findings to allow
      identification and resection of the bleeding lesion. Here the authors report a
      case of severe intestinal bleeding in an infant in whom the intraoperative
      injection of methylene blue dye into a terminal branch of the superior mesenteric
      artery was critical in determining the exact location of bleeding. After accurate
      localization of the bleeding source and segmental intestinal resection, the child
      recovered uneventfully with no recurrence of gastrointestinal bleeding. To the
      authors' knowledge, this is the first reported use of this technique in infancy.

PMID- 9607491
TI  - Junctional epidermolysis bullosa: diagnosis and management of a patient with the
      Herlitz variant.
AB  - A case of Herlitz-type epidermolysis bullosa (EB) is reported. The baby was born
      after a normal, full-term pregnancy with blisters on his extremities. Over the
      next several months, progressive skin sloughing involving 95% of his body surface
      area developed, including gastrointestinal, laryngeal, tracheobronchial, and
      corneal involvement. The diagnosis of junctional EB, Herlitz type, was made using
      clinical, electron microscopic, and immunohistochemical criteria. Despite
      meticulous wound care, aggressive nutritional support, and continuous
      antimicrobial therapy, the baby died at 9 months of age. This report discusses
      the presentation, complications, and management of this unusual and tragic
      disease.

PMID- 9607492
TI  - Hydatid cyst: an unusual etiology for a cystic lesion of the posterior
      mediastinum.
AB  - The cystic lesions of the posterior mediastinum include bronchogenic, enteric and
      intramural esophageal cysts, lymphangioma, and anterior meningocele. Hydatid
      cysts are usually located in the liver, lung, and brain. Although many uncommon
      locations have been reported, hydatid cyst has not previously been encountered as
      an isolated posterior mediastinal lesion. A 4-year-old boy with a posterior
      mediastinal cystic lesion, which has been proven to be a hydatid cyst, is
      reported.

PMID- 9607493
TI  - Splenectomy in a child with chronic Mycobacterium avium complex infection and
      splenic sequestration.
AB  - Mycobacterium avium complex infections (MAC) are being reported with increasing
      frequency in immunocompromised patients. When these infections become resistant
      to standard antibiotic therapy, treatment with interferon-gamma (IFN-gamma) can
      be helpful. Pain, fever, splenic enlargement, and cytopenias caused by splenic
      sequestration developed during IFN-gamma treatment in a 9-year-old boy and were
      successfully treated by splenectomy. The development of IFN-gamma-induced splenic
      sequestration and cytopenias in MAC-infected patients represents a new indication
      for splenectomy.

PMID- 9607494
TI  - Inferior vena caval obstruction from a horseshoe kidney: report of a case with
      operative decompression.
AB  - Horseshoe kidney is a common anomaly with frequent associated anomalies. The
      confluence of the lower poles of the kidneys lies anterior to the inferior vena
      cava. The authors were unable to find any reports in the world's literature of a
      vena caval obstruction caused by the presence of a horseshoe kidney. The authors
      report such a case presenting as bilateral lower leg swelling.

PMID- 9607495
TI  - Fibrous fusion between the liver and the lung: an unusual complication of right
      congenital diaphragmatic hernia.
AB  - A congenital right diaphragmatic hernia was diagnosed in a full-term newborn who
      presented with respiratory distress at the age of 10 hours. The patient required
      respiratory support, and was operated on at age 6 days. During surgery, a central
      defect of the diaphragm was found. The herniated liver was only partially
      reducible because of intrathoracic adhesions. The patient died at 10 days of age
      as a result of persistent fetal circulation. Postmortem pathological examination
      demonstrated a central diaphragmatic defect and a nonseparable fibrous fusion
      between the liver and the lung.

PMID- 9607496
TI  - Expansion and division of conjoined twins.
AB  - Omphalopagus conjoined twins were born by cesarean section after their 24-year
      old gravida 2, para 1 mother went into labor at 35 weeks' gestation. Initial
      studies included roentenograms, an upper gastrointestinal study, small bowel
      follow-through, and computerized tomography with intravenous contrast from neck
      through pelvis. Results of these studies showed that the twins had very little
      shared vasculature, but did share a pericardium and liver parenchyma. The infants
      were allowed to gain weight and grow. After 3 weeks, tissue expanders were placed
      subcutaneously and were rapidly expanded in 2 weeks. The infants were then
      separated. An Argon Beam Coagulator was used to aid the separation of the liver.
      The abdominal fascia was closed primarily on each infant, and the skin easily
      closed without tension. During the first 36 hours of the postoperative course,
      both infants required significant ventilatory support including inhaled nitric
      oxide. After this period, the ventilatory support decreased dramatically and
      rapidly. The infants were discharged 9 days after their surgical separation.
      Conjoined omphalopagus twins, the use of tissue expanders and the Argon Beam
      Coagulator, and the postoperative course are discussed.

PMID- 9607498
TI  - Association of Klinefelter syndrome and abdominal teratoma: a case report.
AB  - Extragonadal germ cell tumors are rare. The association with Klinefelter syndrome
      has become observed recently. A case of an 11-month-old infant with Klinefelter
      syndrome and a retroperitoneal mature teratoma is presented. In the tumor and
      lymphocytes, a 47,XXY karyotype was found. The association of Klinefelter
      syndrome with germ cell tumors and its possible explanations are discussed.

PMID- 9607497
TI  - Cryptococcal rib osteomyelitis in a pediatric patient.
AB  - A case of cryptococcal rib osteomyelitis in a pediatric patient is described.
      Isolated cryptococcal osteomyelitis in pediatric patients is a rare entity, and
      only 10 cases have been reported in the literature. The radiological findings are
      reviewed to include chest films, nuclear bone scan, and computed tomographic
      imaging scan. Because of its rarity, the management of isolated cryptococcal
      osteomyelitis is controversial. Although antifungal antibiotics and surgery are
      the two therapeutic options, the treatment of cryptococcal osteomyelitis has not
      been standardized yet. This patient was treated successfully with limited
      resection of the involved rib and antifungal chemotherapy. This article describes
      the second case in the literature of cryptococcal rib osteomyelitis in a
      pediatric patient, reviews the literature of similar cases, and evaluates the
      current role of surgery in its treatment.

PMID- 9607499
TI  - Open surgical removal of tracheobronchial foreign bodies: a case report.
AB  - Tracheobronchial foreign bodies can usually be extracted by skillful application
      of endoscopic techniques. The authors report on experience in the treatment of an
      infant in whom a plastic object was extracted by an open surgical approach. The
      authors discussed clinical presentation and treatment options in the treatment of
      this patient who had a plastic pencil top lodged in the lung. In highly selected
      cases, an open surgical procedure entails less risk than endoscopic extraction.

PMID- 9607500
TI  - Retroperitoneal necrotizing fasciitis in a 4-year-old girl.
AB  - Necrotizing fasciitis is a rare but serious condition with a poor prognosis both
      in adults and in children. Retroperitoneal localization is mostly associated with
      fatal outcome. Early diagnosis, extensive and repeated surgical debridement, and
      use of antibiotics are necessary. Herein the authors report on a 4-year-old girl
      in whom retroperitoneal necrotizing fasciitis developed after she suffered from
      pyelonephritis. In this case, the outcome was favorable because of early surgical
      intervention, confirming the diagnosis.

PMID- 9607501
TI  - Actinomycotic thyroiditis in a child.
AB  - The authors present a unique case of actinomycosis occurring in a 10-year-old
      girl who presented with a painless, noninflammatory left neck mass of 3 weeks
      duration. Physical examination findings showed a firm, nontender mass within the
      left thyroid lobe, and a presumptive diagnosis of thyroid neoplasm was made.
      Inflammatory changes subsequently occurred and surgical drainage was performed
      revealing sulphur granules. Histological examination confirmed actinomycosis of
      the thyroid gland.

PMID- 9607502
TI  - Successful right trisegmentectomy for ruptured hepatoblastoma with preoperative
      transcatheter arterial embolization.
AB  - This is the first report of the successful use of percutaneous transcatheter
      arterial embolization (TAE) in controlling hemorrhage from ruptured
      hepatoblastoma, allowing early major hepatic resection to be performed safely in
      a young infant. A 6-month-old girl presented with a huge abdominal mass and was
      found to have a hepatoblastoma that measured 15 x 10 x 12 cm and arose from the
      right lobe of her liver on computed tomography (CT) scan examination. The tumor
      spontaneously ruptured, and she went into shock. TAE with gelfoam cube particles
      successfully arrested the tumor bleeding and allowed stabilization of her blood
      pressure with blood transfusion. Right trisegmentectomy was performed 12 hours
      later. The postoperative course was uneventful. With three courses of cisplatin,
      vincristine, and 5-fluorouracil after the hepatectomy, the serum alpha
      fetoprotein level returned to normal, and the patient has remained well 4 months
      postoperation.

PMID- 9607503
TI  - Cystic dysplasia of the testis associated with ipsilateral renal agenesis and
      high anorectal anomalies.
AB  - Scrotal masses in young children are often caused by hydrocoeles and hernias.
      When they arise from the testis, testicular tumor or orchitis, although rare in
      this age group, is often the diagnosis. Cystic dysplasia of the testis, a rare
      condition frequently associated with renal anomalies, is another possible
      differential diagnosis. Herein the authors describe a case in which cystic
      dysplasia of the testis is associated with ipsilateral renal agenesis as well as
      high anorectal anomalies.

PMID- 9607505
TI  - Mesenteric cyst--an unusual presentation.
AB  - Mesenteric and retroperitoneal cysts develop from ectopic lymphatic tissue. Most
      of them present as symptomless abdominal swellings or are found coincidentally
      during abdominal operations. One third of patients may present with acute
      abdominal pain, and few may present with chronic abdominal pain. However,
      mesenteric cyst presenting as inguinal hernia is extremely rare. Only four cases
      have been reported in the English-language literature. The present case is the
      fifth, and only the second from this subcontinent. The treatment of choice is
      complete surgical excision.

PMID- 9607504
TI  - Pancreas divisum and stenosis of the major and minor papillae in an 8-year-old
      girl: treatment by dual sphincteroplasty.
AB  - Pancreas divisum is the most common congenital anomaly of the pancreas. Its
      relationship to the development of pancreatitis is controversial. The authors
      report on an 8-year-old girl who presented with recurrent bouts of acute
      pancreatitis and multiple failed attempts at endoscopic retrograde
      cholangiopancreatography (ERCP) who was referred for surgical exploration. She
      was found to have marked stenoses of both major and minor papillae and an
      intraoperative pancreaticogram consistent with pancreas divisum. She underwent
      sphincteroplasty of both major and minor papillae and remains symptom-free after
      22 months. It is believed that in a patient with pancreatitis and pancreas
      divisum, or in a patient with pancreatitis and multiple failed attempts at ERCP,
      transduodenal exploration and intraoperative pancreaticogram are appropriate next
      steps in management. If pancreas divisum in association with minor papilla
      stenosis is found, sphincteroplasty is appropriate therapy. If major papilla
      stenosis is also present, we recommend sphincteroplasty of both the major and
      minor papillae.

PMID- 9607506
TI  - Hereditary multiple atresias of the gastrointestinal tract: report of a case and
      review of the literature.
AB  - Hereditary multiple atresia of the gastrointestinal tract is an extremely rare
      subgroup of intestinal atresia. The aim of this study was to report a new case,
      to review the literature, and to describe the unique features of this
      malformation. A computer-generated list of articles on this subject was obtained,
      and all articles relative to this malformation were reviewed. Thirty-five other
      well-documented cases were found in the literature. Hereditary multiple atresias
      have several unique features: (1) the abdominal x-ray shows signs of gastric or
      duodenal atresia combined with typical large rounded or oval homogeneous
      calcifications in the abdominal cavity, (2) intraoperatively widespread atresias
      (exclusively type I and II) extending mostly from stomach to rectum are found,
      (3) cystic dilatation of the bile ducts can be present in cases with both
      complete pyloric and duodenal or proximal jejunal atresia, (4) the pathogenesis
      is still speculative; a combined immunodeficiency should be excluded, and (5) a
      fatal outcome is the rule.

PMID- 9607507
TI  - Rectosigmoid bilharzioma causing intestinal obstruction.

PMID- 9607508
TI  - Immediate reconstruction for penile agenesis.

PMID- 9607509
TI  - Serial transabdominal amnioinfusion in the management of gastrochisis with severe
      oligohydramnios.

PMID- 9607510
TI  - Hemispheric asymmetry of the auditory evoked N100m response in relation to the
      crossing point between the central sulcus and Sylvian fissure.
AB  - The positions of the bilateral N100m sources of the auditory evoked magnetic
      fields (AEFs) were measured in relation to the central sulcus (CS) using an MRI
      linked whole head magnetoencephalography system in 20 right-handed normal male
      subjects. The location of the N20m source of the median nerve-stimulated
      somatosensory evoked magnetic fields (SEFs), in the left hemisphere was 3.9+/-5.4
      mm (mean+/-SD) posterior to that in the right hemisphere (P < 0.005). The
      crossing point (CP) between the CS and Sylvian fissure in the left hemisphere was
      4.3+/-4.8 mm posterior to that in the right hemisphere (P < 0.001). The N100m
      sources were posterior to the CP in both hemispheres. The left hemispheric N100m
      source was 9.4+/-6.4 mm posterior to that on the right (P < 0.0001) in absolute
      position. The relative distance between CP and the N100m source was 22.7+/-8.5 mm
      in the left hemisphere and 17.7+/-5.3 mm in the right hemisphere (P < 0.01).
      Comparison of positions of the AEF sources and the CS as defined by the SEF
      demonstrated functional asymmetry of the human temporal lobe and possible source
      extension of the AEF-N100m beyond the Heschl gyrus over the planum temporale.

PMID- 9607511
TI  - Presurgical functional localization of primary somatosensory cortex by dipole
      tracing method of scalp-skull-brain head model applied to somatosensory evoked
      potential.
AB  - The aim of the present study was to explore the utility of dipole tracing (DT) of
      a scalp-skull-brain (SSB) head model in preoperative functional localization of
      the human brain. Nine patients who underwent surgery of mass lesions around the
      central sulcus (CS) were employed. By using SSB/DT, dipole source location of
      early cortical components of the somatosensory evoked potential (SEP) was
      estimated before surgery. Motor cortex, CS and primary somatosensory cortex were
      determined by cortical SEP during surgery. After surgery precise functional
      mapping was reproduced in MRI, and the accuracy of DT was evaluated by measuring
      the distance between estimated dipole source and the posterior bank of the CS. We
      defined this distance as localization error of DT. In 4 cases without structural
      change around the sensorimotor cortex, localization error ranged from 1 to 4 mm
      with an average of 2 mm. In 5 cases with structural alteration of sensorimotor
      cortex, localization error ranged from 6 to 10 mm with an average of 8 mm. The
      difference in localization error between the two groups was statistically
      significant, and may have been caused by changes of conductance near sensorimotor
      cortex in the latter group. Functional localization by DT was accurate and
      useful. But localization error could not be ignored in cases with structural
      alteration in the sensorimotor cortex.

PMID- 9607512
TI  - Cortical localisation of magnetic fields evoked by oesophageal distension.
AB  - Magnetoencephalographic source localisation techniques were used to measure
      oesophageal evoked magnetic fields from the cerebral cortex in 3 subjects. By
      using rapid balloon distension as a stimulus, a comparison of proximal and distal
      oesophageal cortical representation was made. The distal oesophagus was
      represented bilaterally in the insular cortex and SII as well as the inferior
      aspect of SI. The proximal oesophagus was represented unilaterally in superior
      and inferior SI, insular cortex and SII. Significantly, the superior portion of
      SI was consistently activated in subjects following stimulation of the proximal
      oesophagus, but similar activation was not found in response to distal
      stimulation. This may reflect the contribution from somatic afferent fibres in
      the striate muscle of the proximal segment. In conclusion, vagal afferents appear
      to contribute more to cortical activation following stimulation of the distal
      rather than the proximal oesophagus, while spinal afferents appear to be
      activated by both proximal and distal oesophageal stimulation.

PMID- 9607513
TI  - Quantitative trait loci analysis of human event-related brain potentials: P3
      voltage.
AB  - The P3 event-related brain potential (ERP) is a positive-going voltage change of
      scalp-recorded electroencephalographic activity that occurs between 300-500 ms
      after stimulus onset. It is elicited when a stimulus is perceived, memory
      operations are engaged, and attentional resources are allocated toward its
      processing. Because this ERP component reflects fundamental cognitive processing,
      it has found wide utility as an assessment of human mental function in basic and
      clinical studies. In particular, P3 attributes are heritable and have
      demonstrated considerable promise as a means to identify individuals at genetic
      risk for alcoholism. We have conducted a quantitative linkage analysis on a large
      sample from families with a high density of affected individuals. The analyses
      suggest that several regions of the human genome contain genetic loci related to
      the generation of the P3 component of the ERP, which are possible candidate loci
      underlying the functional organization of human neuroelectric activity.

PMID- 9607514
TI  - Dynamic spectral analysis of event-related potentials.
AB  - This paper presents a new method for the identification of individual event
      related potential (ERP) components in both frequency and time domains. Using the
      similar basis function (SBF) algorithm the method provides a time to frequency
      transform, representing a frequency domain equivalent of the component waveform.
      Notable features of the SBF algorithm are that it allows for unevenly spaced
      sampled functions in both the time and frequency domains, and estimates of
      spectral densities are obtained by numerical computation of finite Fourier
      integrals. Application of this method to ERP data from 20 normal subjects
      demonstrated a similar shape of component amplitude frequency characteristics for
      traditional late component waveforms (N1, P2, N2 and P3). On this basis, a low
      frequency band was found where the component amplitude frequency characteristic
      was described by a Gaussian function, while the component phase frequency
      characteristic was a linear function of frequency. These relationships are
      interpreted as frequency domain equivalents of the component. Transformed to the
      time domain, they provided an analytical description of the ERP as the sum of
      positive- and negative-going monopolar waves. The study points to similar
      mechanisms underlying these component waveforms, and analytically defines dynamic
      properties for the components both in the frequency and time domains.

PMID- 9607515
TI  - P3, positive slow wave and working memory load: a study on the functional
      correlates of slow wave activity.
AB  - Parietal positivities of the 'slow wave' type are known to emerge after the P300
      whenever target detection leads to a complex subsidiary task. Although the
      functional correlates of these 'positive slow waves' (PSW) are not known, it has
      been suggested that they may index (a) the selection or decision processes, (b)
      the preparation of the response or (c) the evaluation of its correctness. We
      investigated whether PSW could be dissociated from each of these putative steps
      of information processing by means of a paradigm devoid of motor components and
      needing very long reaction times. In our protocol, target stimuli acted as the
      triggering signal to perform silently one of 4 different tasks, namely (a) simple
      updating of a target count; (b) counting backward in threes; (c) simultaneous
      updating of two items (day of the week and ordinal of the month) and (d) updating
      of 3 items (the two above plus the month of the year). Reaction times to the same
      stimuli were obtained in 5 subjects during separate sessions. The different tasks
      did not modify the latencies of N2 or P3b components, but attenuated the
      amplitude of P3 as a mirror image of the subjective difficulty scores. A
      conspicuous parietal PSW appeared in conditions where two or 3 items had to be
      updated. This PSW developed 1-2 s earlier than the reaction times to the same
      experiments and could be therefore dissociated from the selection and decision
      processes. PSW latency was correlated with the number of items to be updated, but
      not with subjective difficulty. In the present paradigm PSW appeared to index the
      retrieval of information from working memory; however, in more general terms our
      results suggest that PSW is a non-specific activity that signals the completion
      of any synchronized operation immediately following target detection. Our data
      suggest a functional link between P3 and PSW, also supported by the similarity of
      their respective scalp topographies. The present paradigm proved to be easy to
      implement and suitable to study the 'executive' functions governing attentional
      and working-memory control during the performance of multiple tasks.

PMID- 9607516
TI  - Language-related hemispheric asymmetry in healthy subjects and patients with
      temporal lobe epilepsy as studied by event-related brain potentials and
      intracarotid amobarbital test.
AB  - There are current attempts to replace the WADA test for pre-surgical evaluation
      of hemispheric language capabilities by one of the methods of functional brain
      imaging. Recent PET and fMRI studies using verbal cognitive tasks like verb
      generation, semantic monitoring or semantic ('deep') encoding of words showed
      asymmetries of activation in the fronto-lateral cortex. In a previous ERP study
      subjects were required to indicate whether pronounceable non-words and abstract
      geometric figures were presented for the first time ('new item') or whether they
      had been shown before ('old item'). Group analyses of this study showed
      significant material-specific hemispheric asymmetries with ERPs being more
      negative-going in recordings of the posterior part of the left hemisphere with
      verbal material (CP5/6) but more negative-going in recordings of the right
      hemisphere with the spatial material (P7/8). The aim of the present study was to
      test statistically ERP lateralization effects in individual healthy subjects as
      well as WADA-tested patients suffering from seizures of the mesio-temporal lobe
      (MTL). In all subjects ERP lateralization with verbal material was tested in the
      electrode pair CP5/6, and ERP lateralization with figures in the electrode pair
      P7/8. Statistical analyses of single trials showed that in 20 out of 24 subjects
      ERPs with verbal material started to be more negative-going in CP5 as compared to
      CP6 in the period between 100 and 200 ms after stimulus onset or the subsequent
      time epoch (200-300 ms). In one subject not CP5/6 but the closely adjacent
      electrode pair P7/P8 showed this verbal material-related hemispheric effect. In
      patients language dominance as indicated by ERPs was not always consistent with
      the data of the WADA test. In one patient with left MTL seizures ERPs with verbal
      material and figures were found to be significantly lateralized to the right
      hemisphere although the WADA test assigned this patient to have a language
      dominant left hemisphere.

PMID- 9607517
TI  - Auditory event-related potentials to semantic priming during sleep.
AB  - The present study uses the N400 component of event-related potentials (ERPs) as a
      processing marker of single spoken words presented during sleep. Thirteen healthy
      volunteers participated in the study. The auditory ERPs were registered in
      response to a semantic priming paradigm made up of pairs of words (50% related,
      50% unrelated) presented in the waking state and during sleep stages II, III-IV
      and REM. The amplitude, latency and scalp distribution parameters of the
      negativity observed during stage II and the REM stage were contrasted with the
      results obtained in the waking state. The 'N400-like' effect elicited in these
      stages of sleep showed a mean amplitude for pairs of unrelated words
      significantly greater than for related pairs and an increment of latency. These
      results suggest that during these sleep stages a semantic priming effect is
      maintained actively although the lexical processing time increases.

PMID- 9607518
TI  - Replicability of MEG and EEG measures of the auditory N1/N1m-response.
AB  - We investigated the replicability of the source location, amplitude and latency
      measures of the auditory evoked N1 (EEG) and N1m (MEG) responses. Each of the 5
      subjects was measured 6 times in two recording sessions. Responses to monaural
      stimuli were recorded from 122 MEG and 64 EEG channels simultaneously. The EEG
      data were modeled with a symmetrically-located dipole pair. For the MEG data, one
      dipole in each hemisphere was located independently using a subset of channels.
      Standard deviation (SD) was used as a measure for replicability. The average SD
      of the x, y and z coordinates of the contralateral N1m dipole was about 2 mm,
      whereas the corresponding figures for the ipsilateral N1m and the contra- and
      ipsilateral N1 were about twice as large. The SDs of the dipole amplitudes and
      latencies were almost equal with MEG and EEG. The amplitude and latency measures
      of the MEG field gradient waveforms were almost as replicable as those of the
      dipole models. The results suggest that both MEG and EEG can be used for
      investigating the simultaneous activity of the left and right auditory cortices
      independently, MEG being superior in certain experimental setups.

PMID- 9607519
TI  - Topography and morphology of heart action-related EEG potentials.
AB  - Joint ECG and EEG measurements were performed in 22 healthy subjects under
      standardized laboratory conditions. Averaged EEG potentials were computed using
      the R-peaks in the ECG as reference events. Spatio-temporal potential patterns of
      heart action-related EEG activity were obtained from 26 scalp channels. A heart
      action-related positive potential was found, peaking over the parietal scalp
      regions. Its independence from the cardiac electrical field, the source of an EEG
      artifact that may be confounded with heart action-related brain potentials, is
      demonstrated. The potential reaches its maximum amplitude of about 0.5 microV at
      a latency of about 500 ms after the R-peak. Its topography, with peak amplitudes
      at the parietal electrode locations, is different from the topography of
      potentials observed in the few comparable experimental studies published so far.
      This suggests the presence of somatosensory-evoked components in heart action
      related potentials and indicates that a renewed discussion of the underlying
      neuronal processes is necessary.

PMID- 9607520
TI  - Cortical and thalamic visual evoked potentials during sleep-wake states and spike
      wave discharges in the rat.
AB  - Flash visual evoked potentials (VEP) were simultaneously recorded from the
      primary visual cortex and the dorsal lateral geniculate nucleus in freely-moving
      WAG/Rij rats, to investigate whether the thalamic VEP shows the same state
      dependent alterations as the cortical VEP. VEPs obtained during active and
      passive wakefulness (AW and PW), slow-wave sleep (SWS), REM sleep and during the
      occurrence of spike-wave discharges (SWD), a specific trait of the genetically
      epileptic WAG/Rij rat, were compared. The general architecture of the thalamic
      VEP resembles the cortical VEP, although its polarity is reversed. This
      facilitated the interpretation of components in terms of underlying neuronal
      events. The primary excitation peak is differently modulated in cortex and
      thalamus. Whereas the thalamic component (P30) is not affected by brain-state,
      the cortical component (N1) shows a strong increase in latency during SWS and
      SWD. In contrast, the modulation of later components is highly similar for cortex
      and thalamus. VEPs obtained during AW and REM resemble each other. During SWS and
      SWD there is a considerable, and during PW a moderate, enlargement of primarily
      inhibitory components. After-discharges are enhanced during SWS, SWD and REM. No
      evidence is found for a major impairment of sensory transmission during SWD.

PMID- 9607521
TI  - Single-sweep cortical somatosensory evoked potentials: N20 and evoked bursts in
      sevoflurane anaesthesia.
AB  - Cortical evoked responses to median nerve stimulation were recorded from 21
      subjects during sevoflurane anaesthesia at the level of burst suppression in EEG.
      The N20/P22 wave had the typical form of a negative wave postcentrally, and
      positive precentrally. The amplitude exceeded 4 microV in all patients, making it
      easily visible without averaging on the low-amplitude suppression. These results
      show that two kinds of somatosensory evoked potential can be studied without
      averaging during EEG suppression in deep anaesthesia. One is the localised
      N20/P22 wave, which is seen regularly during suppression after stimuli with
      intervals exceeding 1 s. The other is the burst, involving the whole cortex,
      which is not evoked by every stimulus. We suggest that somatosensory evoked
      potentials can be monitored during sevoflurane-induced EEG suppression, and often
      can be evaluated reliably from a couple of single sweeps with stimulation
      interval exceeding 1 s. The enhancement of early cortical components of SEP,
      their adaptation to repeated stimuli, and the disappearance of later polysynaptic
      components during EEG suppression, give new possibilities to study the generators
      of SEP and the different effects of anaesthetics.

PMID- 9607522
TI  - Cancer surgery: why some survival benefits may be artifactual.

PMID- 9607523
TI  - Endoluminal abdominal aortic aneurysm surgery.
AB  - BACKGROUND: The development of devices designed for the endoluminal repair of
      abdominal aortic aneurysm has led to the emergence of new endovascular
      techniques. METHODS: Articles and case reports obtained from a Medline search of
      the English language literature from 1989 to 1997 are reviewed. This search was
      carried out using the MeSH heading 'aortic aneurysm, abdominal' and the keywords
      'endovascular' and 'endoluminal'. RESULTS: Reported mortality and complication
      rates for endoluminal aneurysm repair are similar to those following conventional
      repair, with the exception of continued perfusion of the aneurysm sac which
      remains a major problem following endoluminal repair. CONCLUSION: Successful
      endoluminal aneurysm exclusion is associated with reduced aneurysm diameter.
      However, longer term results of endoluminal repair, in particular of sealed
      endoleaks, are required before randomized controlled trials of endoluminal versus
      conventional repair can be undertaken.

PMID- 9607524
TI  - Lymphocyte function in wound healing and following injury.
AB  - BACKGROUND: Injury activates a cascade of local and systemic immune responses.
      METHODS: A literature review was undertaken of lymphocyte function in wound
      healing and following injury. RESULTS: Lymphocytes are not required for the
      initiation of wound healing, but an intact cellular immune response is essential
      for a normal outcome of tissue repair. Injury affects lymphocyte immune
      mechanisms leading to generalized immunosuppression which, in turn, increases
      host susceptibility to infection and sepsis. Although the exact origin of post
      traumatic immunosuppression remains unknown, stress hormones and
      immunosuppressive factors, such as inflammatory cytokines, prostaglandin E2 and
      nitric oxide, affect lymphocyte function adversely. Post-traumatic impairment of
      T lymphocyte immune function is reflected in decreased lymphocyte numbers, as
      well as altered T cell phenotype and activity. Antibody-producing B lymphocytes
      are variably affected by injury, probably secondary to alterations of T
      lymphocyte function, as a result of their close interaction with helper T cells.
      Therapeutic modulation of the host immune response may include non-specific and
      specific interventions to improve overall defence mechanisms. CONCLUSION: Early
      resuscitation to restore lymphocyte function after injury is important for tissue
      repair and the prevention of immunosuppression.

PMID- 9607525
TI  - Non-operative management of blunt hepatic trauma.
AB  - BACKGROUND: Non-operative management is currently considered the treatment of
      choice in over 50 per cent of adult patients with blunt liver injury. This report
      reviews the criteria for non-operative management and its potential downside.
      METHODS: English language publications were reviewed. RESULTS: Most reports from
      major trauma centres in the USA support the non-operative treatment of patients
      with blunt liver injury if well established criteria are met. Using such
      criteria, non-operative treatment is successful in 50-80 per cent of cases.
      Adjunctive radiological techniques may be helpful in managing some complications
      of non-operative treatment. CONCLUSION: Non-operative management is safe in
      haemodynamically stable patients with blunt liver injury. Computed tomography
      (CT) of the abdomen is extremely useful to document the extent of the damage and
      the presence of associated injuries, but it is not possible, based on CT alone,
      to predict failure; careful physiological monitoring in selected patients is
      indicated to avoid catastrophic complications.

PMID- 9607526
TI  - Early colorectal cancer: recognition, classification and treatment.
AB  - BACKGROUND: With the introduction of colorectal cancer screening and improvements
      in endoscopic technology, the recognition and management of early colorectal
      cancer assumes increasing importance. METHODS: A literature review was undertaken
      using Medline (National Library of Medicine, Washington DC, USA) searches of the
      headings early colonic, colorectal and rectal cancer, carcinoma and
      adenocarcinoma up to and including 1997. All relevant references were examined.
      RESULTS AND CONCLUSION: The diagnosis, classification and treatment options are
      described. Accurate diagnosis, preoperative and histopathological staging is
      crucial in the management of early colorectal cancer.

PMID- 9607527
TI  - Circulating bile is the main factor responsible for atrial natriuretic peptide
      release in experimental obstructive jaundice.
AB  - BACKGROUND: Biliary obstruction in the rabbit causes increased release of atrial
      natriuretic peptide (ANP). Circulating bile, raised biliary pressure or absence
      of bile in the duodenum may be implicated in this hepatocardiac syndrome.
      METHODS: An experimental model was developed to elucidate the mechanism linking
      obstructive jaundice and increased plasma ANP. Hepatic and renal function,
      biliary tree pressure and ANP plasma concentrations were investigated in
      conscious rabbits 4 and 24 h after common bile duct ligation, biliovenous
      shunting or external drainage via a biliary fistula. RESULTS: Bilirubin
      concentration increased after bile duct ligation and creation of a biliovenous
      shunt. Plasma creatinine increased abruptly in rabbits with a biliovenous shunt.
      At 4 h, the ANP increase in animals with a biliovenous shunt was ninefold that
      observed after bile duct obstruction while no change was noted after external
      biliary diversion (mean 350 versus 45 versus 9 fmol/l; P < 0.01). Relief of
      biliary tree obstruction was associated with a return of ANP levels towards basal
      normal values. CONCLUSION: Raised plasma ANP in obstructive jaundice is not the
      result of an increased biliary pressure per se or absence of bile in the proximal
      duodenum but of the passage of bile components to the circulation.

PMID- 9607528
TI  - Total vascular exclusion of the liver for the resection of lesions in contact
      with the vena cava or the hepatic veins.
AB  - BACKGROUND: This study reviews experience with total vascular exclusion of the
      liver (TVE), for the resection of tumours in contact with the hepatic veins or
      the vena cava. METHODS: A retrospective study was carried out of 366 hepatic
      resections performed over 13 years. Forty-one patients (11 per cent) were
      operated under TVE. RESULTS: Twenty-four patients were operated for malignancy
      and 17 for benign disease. Major hepatectomy was performed in 26 patients and
      minor hepatectomy in 15. The technique allowed vascular repair in eight patients.
      Median intraoperative blood transfusion was 2 (range 0-26) units; 14 patients
      required none. Median duration of TVE was 29 (range 5-58) min. No deaths
      occurred. Significant complications occurred in ten patients. Morbidity was
      related to the malignant nature of the lesion, duration of surgery and volume of
      blood transfusion, but not to duration of TVE. CONCLUSION: TVE facilitates
      resection of critically located hepatic lesions with safety and minimal blood
      loss. Within the limits of 1 h, prolonged TVE does not increase morbidity.

PMID- 9607529
TI  - Prospective randomized trial of systemic antibiotics in patients undergoing liver
      resection.
AB  - BACKGROUND: Systemic antibiotics are administered frequently after hepatectomy to
      prevent infective complications, but their effectiveness is uncertain. METHODS: A
      total of 127 patients with liver tumours were prospectively randomized into two
      groups after hepatectomy: in group 1 (62 patients) no antibiotics were given
      until the appearance of infective complications; in group 2 (65 patients)
      intravenous cephazolin 1 g every 6 h and gentamicin 80 mg every 8 h were given
      for 7 days. On the day before surgery all patients received bowel preparation by
      clear liquid diet and oral antibiotics (neomycin 1 g and erythromycin 1 g, given
      together in three doses). RESULTS: The infective complication rate was 23 per
      cent in both groups (P = 0.95). The hospital costs were higher in group 2 (P <
      0.001). Of the group 1 patients, 51 (82 per cent) did not require antibiotic
      treatment. No patient in either group died after hepatectomy. CONCLUSION:
      Postoperative systemic antibiotics cannot prevent infective complications, and
      their routine use after hepatectomy is unnecessary and costly. The use of
      antibiotics should be delayed until infective complications and persistent septic
      symptoms occur.

PMID- 9607530
TI  - Encouraging results of split-liver transplantation.
AB  - BACKGROUND: Liver donor shortage presently accounts for a 10 per cent waiting
      list mortality rate. Split-liver transplantation (SLT) can improve utilization of
      this scarce resource. METHODS: Twenty-four SLTs (11 left, 13 right grafts) from
      13 livers were performed in 23 patients (nine adults, 14 children), comprising
      4.5 per cent of all orthotopic liver transplants (14 urgent or emergency, ten
      elective). The left graft comprised segments II and III, whereas the right graft
      comprised segments V-VIII in eight cases, IV-VIII in three, and segments I, IV
      VIII, and I, V-VIII in one case each. Additional arterial extension grafts were
      required in six of 24 cases, and portal venous interposition graft in one.
      RESULTS: Twenty-one grafts showed good initial function, with one primary non
      function and two initial poor function. The median peak aspartate
      aminotransferase level was 782 (range 94-2301) and 982 (range 382-2520) units/l
      for left and right grafts respectively. Five patients died (all urgent
      recipients), all within the first 30 days after surgery. Two SLT recipients
      underwent subsequent retransplantation. All ten elective recipients are alive.
      The 1-year actuarial patient and graft survival rates at a median follow-up of 20
      months were 78 and 68 per cent respectively. CONCLUSION: These encouraging
      results compare favourably with those of reduced-size and whole-liver
      transplantation and justify wider application of this technique, thereby
      optimizing donor resource use.

PMID- 9607531
TI  - Carcinoma of the head of the pancreas arising from the uncinate process.
AB  - BACKGROUND: Carcinoma located in the uncinate process (CUP) of the pancreatic
      head is considered to be rare. Exact epidemiological data, however, are not
      available because the series published so far consist of fewer than ten patients.
      The purpose of this prospective study was to evaluate the clinical appearance of
      CUP and to compare findings with those of patients with carcinoma in the ventral
      aspect of the pancreatic head (VPC), which represents the most frequent
      localization. RESULTS: Some 39 (8 per cent) of 506 evaluated patients suffered
      from CUP. Mean age was 63.3 years. The most frequent complaints were upper
      abdominal pain (n = 32) and weight loss (n = 35). Jaundice was seen in only five
      patients and was never an early symptom. The level of CA19-9 was raised in 33
      patients. The best diagnostic procedure to detect CUP was computed tomography
      (CT) (sensitivity 93 per cent), whereas endoscopic retrograde
      cholangiopancreatography was not useful (sensitivity 21 per cent). Vascular
      involvement was significantly (P < 0.01) more common in CUP (n = 19) than in VPC
      (48 versus 19 per cent). This finding and the fact that most patients with CUP
      were diagnosed at a late stage with distant metastasis or severe vascular
      involvement present (n = 21) are responsible for the significantly lower rate of
      operation (n = 25) (64 versus 92 per cent, P < 0.05) and the significantly
      shorter median survival time (5 versus 11 months, P < 0.05). CONCLUSION: Patients
      with CUP have a poor prognosis as a result of the lack of early symptoms
      (jaundice) and early vascular involvement due to the proximity of the uncinate
      process to the mesenteric root. A raised level of CA19-9, together with weight
      loss and/or upper abdominal pain, should prompt CT.

PMID- 9607533
TI  - Carotid endarterectomy is safe in selected elderly patients.

PMID- 9607532
TI  - Raised endothelin 1 levels in patients with colorectal liver metastases.
AB  - BACKGROUND: Endothelin 1 (ET-1), a vasoconstrictor peptide, has been implicated
      as a tumour growth stimulator and an angiogenesis factor. METHODS: To assess the
      involvement of ET-1 in colorectal cancer, immunoelectron microscopy for ET-1 was
      performed in colorectal liver metastases and normal liver (n = 6). ET-1 plasma
      levels were measured by radioimmunoassay in patients with colorectal cancer, with
      (n = 18) and without (n = 12) liver metastases, and in controls (n = 22).
      RESULTS: In normal liver, ET-1 was present in endothelial cells; in tumour, it
      was observed in endothelial cells, tumour cells and myofibroblasts. Mean(s.d.)
      plasma ET-1 levels were 2.75 (1.37) pg/ml in controls, 4.53(1.61) pg/ml in
      patients with colorectal liver metastases (P = 0.001) and 3.92(1.32) pg/ml in
      patients without metastases (P = 0.02). CONCLUSION: ET-1 was present in various
      cell types within colorectal liver metastases and raised levels were found in the
      plasma of patients with colorectal cancer. ET-1 may not only modulate tumour
      vascular tone but also act on tumour growth and angiogenesis, both locally and
      systemically.

PMID- 9607534
TI  - Trials and tribulations of vascular surgical benchmarking.
AB  - BACKGROUND: Benchmarking is a new tool to assess the efficiency of different
      hospitals. Classification of operations using healthcare resource groups (HRGs)
      is related to parameters including number of cases, length of stay (LOS) and age
      profile. METHODS: A National Comparative Database was used to compare three
      hospitals. Analysis was confined to the major HRGs involved with vascular/venous
      surgery. RESULTS: For high-volume low-complexity varicose vein surgery, all three
      hospitals had similar numbers of patients and LOS. In contrast, the LOS for
      routine vascular operations in hospital A was double that in hospital B (16.3
      versus 7.4 days). Hospital A had three times as many patients classified as
      'other - peripheral vascular disease' as hospital C and six times as many as
      hospital B (329, 49 and 111 for hospitals A, B and C respectively). LOS following
      major amputation in hospitals A and C was nearly double that in hospital B (32.4,
      18.3 and 33.6 days for hospitals A, B and C respectively). CONCLUSION: There were
      a number of significant variations between the three hospitals during the 9-month
      interval. Explanations included the methods of coding, local facilities including
      availability of rehabilitation beds and difference in the patients' age profiles.
      Benchmarking in its present format reveals a number of variations which may not
      necessarily reflect real differences in clinical performance.

PMID- 9607535
TI  - Cryopreserved aortic homografts for patients who need simultaneous aortic and
      gastrointestinal surgery.

PMID- 9607536
TI  - Ruptured hepatocellular carcinoma as a complication of transarterial oily
      chemoembolization.
AB  - BACKGROUND: Transarterial oily chemoembolization (TOCE) is frequently employed as
      a non-operative treatment for hepatocellular carcinoma (HCC). Serious
      complications of TOCE are well known but ruptured HCC as a fatal complication of
      TOCE has not been reported previously. METHODS: A retrospective study was
      performed on all patients who received TOCE for treatment of HCC from January
      1989 to October 1996; the complication of ruptured HCC within 2 weeks from the
      procedure was recorded. RESULTS: During the study period, 391 patients received a
      total of 1443 sessions of TOCE (mean 3.7 sessions per patient) for the treatment
      of HCC, with an overall median survival of 10.4 months. Six patients developed
      ruptured tumour within 2 weeks after TOCE, resulting in an overall incidence of
      1.5 per cent per patient or 0.4 per cent per procedure. All except one patient
      died 1-25 days after tumour rupture. Factors common to these six patients
      included: (1) male sex; (2) large tumour size (range 8-17 cm in diameter); (3)
      tumour located in the right lobe of the liver; (4) tumour ruptured after the
      first session of TOCE; and (5) TOCE performed as primary treatment without
      previous hepatic resection. CONCLUSION: Ruptured HCC is a serious complication of
      TOCE although the incidence is low. It occurred predominantly in men after the
      first session of TOCE for a large irresectable tumour of the right lobe.

PMID- 9607537
TI  - Improved survival in patients with rectal cancer: a population-based register
      study.
AB  - BACKGROUND: Between 1985 and 1989, only one centre in Sweden combined
      preoperative radiotherapy with total mesorectal excision (TME) in the primary
      treatment of rectal cancer. The aim of this study was to investigate whether this
      change in primary treatment had an impact on the outcome. METHOD: The survival
      rate of 94,262 patients with colorectal cancer from the total Swedish population
      between 1960 and 1989 was analysed. RESULTS: A continuous improvement in relative
      survival rate occurred during the first year of follow-up for both colonic and
      rectal cancer. Some improvement was also seen during follow-up years 2-5, but
      this was much more pronounced during the last period (1985-1989) for rectal
      cancer in the county of Uppsala. The improvement was particularly marked during
      follow-up years 3-5. CONCLUSION: There are strong indications from this study
      that altered primary treatment for rectal cancer results in improved long-term
      survival.

PMID- 9607538
TI  - Local anal hypothermia with a frozen finger: a treatment for acute painful
      prolapsed piles.

PMID- 9607539
TI  - Significance of local recurrence of rectal cancer as a local or disseminated
      disease.
AB  - BACKGROUND: The nature of 'local recurrence' of rectal cancer remains unclear.
      METHODS: Fifty-nine patients with locally recurrent rectal cancer who underwent
      extended repeat resections including total pelvic exenteration (39) and
      sacrectomy (43) were reviewed. Twelve patients had distant metastases before or
      at the time of repeat resection. RESULTS: The 5-year survival rate was 25 per
      cent. A second recurrence occurred in 45 patients including five of the eight 5
      year survivors. Thirty-six of these recurrences had locoregional manifestations
      and 29 had distant metastases. Of 18 prognostic factors examined, the most
      significant determinant was the postoperative carcinoembryonic antigen doubling
      time (CEADT), followed by the preoperative CEADT, carcinoembryonic antigen (CEA)
      level and occurrence of distant metastases, in decreasing order. Late onset of
      first recurrence was also a favourable indicator. Thus, the growth rate of the
      tumour had a more profound impact on survival than the current extent of tumour
      progression. After operation the CEADT was reduced in patients with second
      recurrence (P = 0.05). CONCLUSION: Locally recurrent rectal cancer is a
      manifestation of disseminated disease spreading locoregionally and often to
      distant organs with a low probability of long-term cure. However, survival varies
      widely depending on the tumour growth rate, which is biologically predetermined
      and is also influenced by surgery.

PMID- 9607540
TI  - Effect of the introduction of total mesorectal excision for the treatment of
      rectal cancer.
AB  - BACKGROUND: Total mesorectal excision (TME) has been reported to reduce local
      recurrence and improve survival rates in patients with rectal carcinoma. This
      paper reports the problems that have arisen with the introduction of this new
      surgical technique. METHODS: This was a prospective study of two consecutive
      groups of patients: one who underwent TME (n = 76) and one who did not (non-TME,
      n = 76). RESULTS: Postoperative mortality rate in the non-TME and TME group was 5
      and 7 per cent respectively, and the rate of anastomotic failure was 8 and 16 per
      cent respectively. Anastomotic leaks in TME patients were located in the mid and
      lower rectum. TME patients with anastomotic failure had lower anastomoses and a
      longer duration of operation than non-TME patients. Intraoperative problems were
      encountered in 71 per cent of the failures. All TME patients who had a leak
      required reoperation compared with 25 per cent of non-TME patients. TME patients
      without postoperative complications stayed significantly longer in hospital than
      non-TME patients. CONCLUSION: Anastomotic dehiscence increased after introduction
      of the TME technique but this improved with experience.

PMID- 9607541
TI  - Abdominal ultrasonography in the diagnosis of colonic cancer.
AB  - BACKGROUND: Colonic cancer is normally diagnosed by barium enema or colonoscopy.
      Neither investigation is ideal, especially in the elderly patient. This study
      investigates the potential role of abdominal ultrasonography in the diagnosis of
      colorectal carcinoma. METHODS: Fifty-four patients with known or suspected
      colonic carcinoma were referred for abdominal ultrasonography. A single
      radiologist performed scans on these patients and the site of any colonic mass or
      wall thickening considered to be consistent with a colonic carcinoma was
      reported. All carcinomas were confirmed by histology on tissue obtained at
      colonoscopy or surgery against which the ultrasonographic diagnosis was compared.
      Colonic masses detected in patients undergoing routine abdominal ultrasonography
      for abdominal symptoms were also reported. RESULTS: Forty-five of the 54 patients
      referred had colonic carcinoma and abdominal ultrasonography detected 43 of the
      tumours and correctly identified the site of 41. The sensitivity, specificity and
      accuracy of abdominal ultrasonography in the detection of colonic tumours
      considered to be consistent with a colonic carcinoma was 96, 67 and 91 per cent
      respectively. Seven tumours were identified in patients referred before any other
      investigation had been carried out. CONCLUSION: Abdominal ultrasonography may
      detect a colonic mass or wall thickening consistent with a colonic carcinoma with
      a high degree of accuracy and may be useful when barium enema or colonoscopy is
      not possible.

PMID- 9607542
TI  - Influence of blood components and faeces on the in vitro cancericidal activity of
      povidone-iodine.
AB  - BACKGROUND: Tumoricidal agents have been used to kill viable exfoliated tumour
      cells following colorectal cancer surgery. Recent in vivo experiments have thrown
      some doubt on the tumoricidal activity of povidone-iodine. METHODS: The cytotoxic
      effect of distilled water and of povidone-iodine at 0.04, 0.4, 0.8, 2 and 4 per
      cent final concentrations on human SW620 colonic cancer cells in the presence of
      red blood cells, purified haemoglobin and red blood cell (RBC) membranes, plasma,
      albumin, faeces and bacteria was investigated. Cell viability was assessed using
      the trypan blue assay and MTT test. RESULTS: The presence of albumin and plasma
      decreased the tumoricidal activity of povidone-iodine except for the highest
      concentration tested. Bacterial suspension did not influence the efficacy of
      povidone-iodine. Faecal material was found to have an intrinsic tumoricidal
      effect. Both intact and lysed RBCs very strongly inhibited the tumoricidal
      activity of all povidone-iodine concentrations tested. This inhibitory effect was
      due to haemoglobin, but not to RBC membranes. CONCLUSIONS: Low concentrations of
      povidone-iodine fail to kill all 'exfoliated' cancer cells in the presence of
      proteins, intact or lysed RBCs. Therefore, washing out of these organic materials
      before application of a relatively high povidone-iodine concentration (e.g. 5 per
      cent or greater) may be more useful in killing viable exfoliated tumour cells
      during surgery for colorectal cancer.

PMID- 9607543
TI  - Histamine in human breast cancer.
AB  - BACKGROUND: Histamine inhibits lymphocyte function in vitro at concentrations of
      greater than 10(-6) mol/l. The aim of this study was to determine whether
      histamine concentrations in breast cancers were sufficient to produce an
      immunological effect. METHODS: Tumour and adjacent normal breast content of
      histamine was measured using a radioenzymatic assay in 29 patients having surgery
      for breast cancer. RESULTS: The median content of histamine in breast cancer
      tissue was 5.4 (range 0.9-27.3) microg/g (median concentration 4.5 x 10(-5)
      mol/l), and was significantly greater than that in adjacent breast tissue (P =
      0.007). CONCLUSION: The concentration of histamine in breast cancer was
      sufficient to inhibit lymphocyte function and could be locally immunosuppressive.

PMID- 9607544
TI  - Long-term beneficial effects of a gastric reservoir on weight control after total
      gastrectomy: a study of potential mechanisms.
AB  - BACKGROUND: Weight loss after total gastrectomy is a regular occurrence.
      Reconstruction with a gastric substitute has been suggested to facilitate
      recovery, but few randomized studies are available. METHODS: In a randomized
      study comparing subtotal, total and total gastrectomy with an S-shaped pouch, 36
      patients who had total gastrectomy with or without a pouch survived for more than
      3 (mean 5.2) years. Body composition (four-chamber model, dual-energy X-ray
      absorptiometry, anthropometric data) was evaluated before operation, after 12
      months and at long-term follow-up. Food intake was registered as a 4-day food
      record at 12 months and at long-term follow-up. RESULTS: At long-term follow-up
      those allocated to the gastric substitute arm had lesser degrees of weight loss
      consisting mainly of the depletion of body fat stores, whereas lean body mass
      showed no significant decrease when adjusted for the process of ageing. There was
      no significant difference in food intake. CONCLUSION: Reconstruction with an S
      shaped gastric substitute facilitates long-term recovery after total gastrectomy
      and should be considered when the prognosis is favourable.

PMID- 9607546
TI  - Popliteal vein reflux reduces the healing of chronic venous ulcer.

PMID- 9607545
TI  - Relation between tumour necrosis factor alpha and interleukin 1beta producing
      capacity of peripheral monocytes and pulmonary complications following
      oesophagectomy.
AB  - BACKGROUND: Adult respiratory distress syndrome and pneumonia remain a
      significant cause of morbidity and death following oesophagectomy. The aim of
      this study was to clarify the association between tumour necrosis factor (TNF)
      alpha and interleukin (IL) 1beta with these pulmonary complications. METHODS: The
      in vitro TNF-alpha and IL-1beta producing capacity of peripheral monocytes with
      or without lipopolysaccaride (LPS) and serum level of IL-6 was measured in 19
      patients with oesophageal cancer before and after surgery and in ten age-matched
      controls. RESULTS: Six patients had raised TNF-alpha and IL-1beta producing
      capacity of monocytes without LPS both before operation and on the day after
      surgery. In these patients plasma elastase and serum IL-6 levels subsequently
      increased while the ratio of arterial partial pressure of oxygen to fraction
      inspired oxygen decreased, and they developed bilateral lung infiltration on
      chest radiography on days 3-7. Five of the six developed pneumonia compared with
      none of the remaining 13 patients (P < 0.05). CONCLUSION: Pulmonary impairment
      and pneumonia following oesophageal surgery was associated with raised monocyte
      producing capacity of TNF-alpha and IL-1beta. These markers may be valuable in
      the preoperative assessment of patients awaiting oesophagectomy.

PMID- 9607547
TI  - Predicting changes in the distribution of sweating following thoracoscopic
      sympathectomy.

PMID- 9607548
TI  - Hereditary breast cancer.

PMID- 9607549
TI  - Laparoscopy for the impalpable testis.

PMID- 9607550
TI  - Helicobacter pylori and peptic ulcer surgery.

PMID- 9607551
TI  - Early effect of carotid endarterectomy on arterial blood pressure measured with
      an ambulatory monitor.

PMID- 9607552
TI  - Enhancing the efficacy of radical prostatectomy in locally advanced prostate
      cancer.
AB  - Locally advanced prostate cancer patients comprise those with iatrogenic capsular
      injury, extracapsular extension resulting in positive surgical margins following
      radical prostatectomy, and tumors with lymph node metastases, thus representing
      stage T3,N0,M0 or T1-4,N1-2,M0 disease. Parameters can be combined, as shown
      below, in a nomogram to predict advanced prostate cancer: if, for example, stage
      T2c is coupled with a PSA of 16 ng/ml and a high Gleason grade, the patient will
      have an approximately 70% likelihood of having extracapsular extension; then
      again, if the Gleason score is known from biopsies and a PSA of 10-20 ng/ml is
      given, then a stage T2c prostate cancer patient with a Gleason of 7 will have a
      39% probability of having positive lymph nodes. The following therapeutic
      considerations may be used to enhance the chance of eradicating advanced disease
      through radical prostatectomy: (1) Neoadjuvant hormonal therapy helps downsize
      the tumor and may eventually reduce the number of positive margins by almost 50%.
      However, it is a moot point if this will lead to a prolonged survival period. (2)
      Technical refinements on radical prostatectomy may be achieved through the
      principle of wide extension excision, a modification of current apical dissection
      procedures, which involves the use of panoramic magnifying loupes, and an
      examination of resection margins during surgery using repetitive frozen sections.
      (3) If positive (not simply 'equivocal' as defined by Epstein) margins are found,
      radical prostatectomy alone is not curative. Among the various options available
      is postoperative irradiation with or without adjuvant hormonal therapy. The
      latter should probably be reserved for patients with extracapsular extension, a
      high Gleason score or positive lymph nodes. Hormonal therapy may be used
      continuously or intermittently. The value of adjuvant treatment is currently
      being tested in phase-III trials. (4) Hormonal therapy may be commenced at the
      time of biochemical or clinical progression, although it is not clear whether
      this modality is inferior to adjuvant forms of treatment. Technical expertise in
      radical prostatectomy accumulated at major institutions can be used to the
      advantage of patients with locally advanced prostate cancer. In this regard,
      results of ongoing phase-III trials testing various options including this
      procedure are eagerly awaited.

PMID- 9607553
TI  - Leuprorelin 1-month depot as neoadjuvant therapy for prostate cancer. Takeda NHT
      Italian Group.
AB  - In the last few years, the role of neoadjuvant hormonal treatment (NHT) prior to
      radical prostatectomy has been largely debated and investigated in randomized
      multicenter trials as well as in large single-institution studies. We have
      initiated a prospective randomized comparative trial with parallel groups in
      patients with clinically limited disease to contribute to the clarification of
      the possible role of NHT; to evaluate the efficacy of NHT with leuprolide plus
      cyproterone acetate in 'maintaining' the stage of the disease; to reduce the
      percentage of pathological overstaging, and mainly to accurately assess the
      pathological modifications induced by NHT. The present paper is an interim report
      of the results.

PMID- 9607554
TI  - Leuprorelin three-month depot in the treatment of advanced and metastatic
      prostate cancer: long-term follow-up results.
AB  - OBJECTIVES: To determine median survival time, median time to tumor progression
      and maintenance of testosterone suppression (i.e. < or = 50 ng/dl) during long
      term treatment with subcutaneous injections of leuprorelin acetate 3-month depot
      (LAD-3M). In Germany 62 patients with advanced prostate cancer participated in a
      prospective, randomized, multicenter phase II trial as part of a European study.
      Of these, 37 patients entered the follow-up study. METHODS: Standard clinical
      investigations and methods were employed in the study. RESULTS: Twenty-five of
      the 62 (40.3%) patients died during the course of the study. No death had a
      causal relationship with the study drug. Median survival time, median time to
      tumor progression and median period of progression-free survival were 1,149 (3.1
      years), 1,015 (2.8 years) and 680 days (1.9 years), respectively. Adequate
      suppression of testosterone serum levels to the castration range was confirmed.
      Objective and subjective response as well as the safety profile were comparable
      to previously published results with LAD-3M, LAD-1 M and other LHRH analogues.
      CONCLUSIONS: The results of this follow-up study confirm long-term efficacy and
      safety of LAD-3M for treatment in advanced prostate cancer. LAD-3M is a suitable
      alternative to the established shorter-acting LHRH-a depot formulations.

PMID- 9607555
TI  - Artificial urinary sphincter AMS 800 for urinary incontinence after radical
      prostatectomy: the French experience.
AB  - Post-radical prostatectomy urinary incontinence (PRP-UI) has a major negative
      impact on the patient's quality of life with the incidence accounting for over
      30% on a patient questionnaire basis. In 1995 the French Urological Association
      started a prospective survey to investigate the efficacy and safety of the AMS
      800 artificial urinary sphincter (AUS) in PRP-UI, and preliminary results are
      presented for the 103 men enrolled in the study in whom bulbar urethral cuff
      placement was used exclusively. Surgical revision was necessary in 22 patients
      (21%). Infection and erosion accounted for 12 non-mechanical revisions leading to
      complete removal of 6 AUS and to eventual replacement of 6 devices with new ones.
      Mechanical malfunction accounted for revision in l0 patients (9.7%). Fifty-nine
      patients (61.45%) reported no leakage for the 96 working devices. Twenty-seven
      patients (28%) wore no pads, 3 patients used 1 pad and 4 patients used 2
      pads/day, and all these patients reported improvement, with only 3 patients (3%)
      having had more than 2 pads/day. Currently, no non-prosthetic procedure reliably
      affords such good objective results. Insertion of the AMS 800 AUS no doubt
      represents an attractive treatment modality available for male urinary
      incontinence following radical prostatectomy.

PMID- 9607556
TI  - Hereditary prostate cancer and other genetic predispositions to prostate cancer.
AB  - The incidence of prostate cancer (CaP) and its increase in the last 10 years vary
      both from country to country and according to the ethnic group, with the highest
      incidence reported for Afro-Americans and the lowest for Asian men. To date, only
      three risk factors have been established for CaP: age; familial aggregation of
      CaP, and ethnic origins. No dietary or environment-related cause has been
      established. However, some variations in endogenous genetic factors may help
      explain differences in risk among ethnic groups or geographic areas. Similarly,
      certain genetic polymorphisms of genes encoding for 5alpha-reductase, androgen
      receptor or vitamin D, have been associated with different levels of CaP risk,
      and could explain the variations observed between populations. Different studies
      support the view that familial CaP may truly be hereditary, and not due to a
      similar lifestyle. Thus, familial inheritance is a parameter that needs to be
      considered in recommending screening for high-risk families. Indeed, when 1, 2,
      and 3 first-degree relatives are affected, the relative risk of first-degree
      relatives of CaP patients may increase to 2, 5, and 11%, respectively. Some
      familial forms appear to be associated with transmission of a rare putative
      dominant gene with a high penetrance (88% at age 85), with the cumulative
      proportion of CaP attributable to this gene being more marked for younger
      patients (a 43 versus a 34% risk of CaP appearing before the age of 55 versus 70
      years). Using this transmission model and linkage analysis, a predisposing locus
      on chromosome 1q24-25 (HPC-1) has been described. Moreover, recessive and X
      linked transmission has been suggested, showing that a large proportion of
      familial CaP may not be due to segregation of a few major gene mutations, but
      rather to familial sharing of alleles at many loci, each contributing to a small
      increase in cancer risk. Candidate genes may be the same suppressor genes that
      are involved in other cancers and in sporadic CaP.

PMID- 9607557
TI  - Differential effects of hepatocyte growth factor isoforms on epithelial and
      endothelial tubulogenesis.
AB  - Hepatocyte growth factor (HGF)/scatter factor (SF) is a pleiotropic cytokine that
      acts as a mitogen, motogen, and morphogen for a variety of cell types. HGF/NK1
      and HGF/NK2 are two naturally occurring truncated variants of HGF/SF, which
      extend from the NH2 terminus through the first and second kringle domain,
      respectively. Although these variants have been reported to have agonistic or
      antagonistic activity relative to HGF/SF in assays of cell proliferation and
      motility, their potential morphogenic activity has not been investigated. To
      address this issue, we assessed the ability of HGF/NK1 and HGF/NK2 to induce tube
      formation by (a) MCF-10A mammary epithelial cells grown within collagen gels and
      (b) human umbilical vein endothelial (HUVE) cells grown on Matrigel. We found
      that HGF/NK1 stimulated tubulogenesis by both MCF-10A and HUVE cells, whereas
      HGF/NK2 did not stimulate tubulogenesis, but efficiently antagonized the
      morphogenic effect of full-length HGF/SF. HGF/NK1 and HGF/NK2 also had agonistic
      and antagonistic effects, respectively, on MCF-10A cell proliferation and HUVE
      cell migration. These results demonstrate that HGF/NK1, which only consists of
      the NH2-terminal hairpin and first kringle domain, is sufficient to activate the
      intracellular signaling pathways required to induce morphogenic responses in
      epithelial and endothelial cells. In contrast, HGF/NK2, which differs from HGF/
      NK1 by the presence of the second kringle domain, is devoid of intrinsic activity
      but opposes the effects of HGF/SF. The differential properties of the two HGF/SF
      isoforms provide a basis for the design of more potent HGF/SF agonists and
      antagonists.

PMID- 9607558
TI  - Isolation of temperature-sensitive mutations in the c-raf-1 catalytic domain and
      expression of conditionally active and dominant-defective forms of Raf-1 in
      cultured mammalian cells.
AB  - The c-Raf-1 kinase is converted into an oncoprotein by functional inactivation of
      its NH2-terminal regulatory domain and into a dominant-interfering protein by
      mutations that eliminate catalytic activity. This report describes a systematic
      charged residue-to-alanine scanning mutagenesis of the ATP-binding subdomain of
      the c-raf-1 gene. Two temperature-sensitive mutations were found, which were then
      used to construct both conditionally active and conditionally dominant-defective
      alleles. Stable cell lines overexpressing both types of mutants were isolated,
      and their phenotypes were examined. Ectopic expression of Raf-1 activity in
      quiescent cells was not sufficient to elicit S-phase entry, but the Raf signal
      could be efficiently complemented by the progression factor insulin-like growth
      factor I. The results point to a function of Raf-1 in the platelet-derived growth
      factor and epidermal growth factor pathways, leading to the establishment of
      competence for cell cycle entry. Ectopic expression of the dominant-defective
      activity in quiescent cells efficiently blocked entry into S phase. Effects of
      the dominant-defective protein could be detected minutes after the shift to the
      restrictive conditions and resulted in the rapid down-regulation of the mitogen
      activated protein kinase pathway. Taken together, the phenotypes of the
      conditionally active and conditionally dominant-defective mutants point to a
      critical function of Raf-1 at very early times during exit from G0 and entry into
      G1.

PMID- 9607559
TI  - Effects of procollagen C-proteinase enhancer protein on the growth of cultured
      rat fibroblasts revealed by an excisable retroviral vector.
AB  - An excisable retroviral vector, TSN-lox, was developed by exploiting Cre-loxP
      homologous recombination. An integrated TSN-lox provirus could be excised,
      leaving a solo long terminal repeat at the integration site; inverse PCR, taking
      advantage of the solo long terminal repeat, was used to characterize cellular
      flanking sequences. A TSN-lox-transduced Rat2 cell clone, lox-7, was found to
      harbor the provirus in an intron of the procollagen C-proteinase enhancer protein
      (PCPE) gene, whose expression was lowered compared with that of the parental
      Rat2. When the vector provirus in lox-7 cells was excised, PCPE expression was
      elevated. The level of PCPE expression seemed to affect cell growth properties
      such as morphology, contact inhibition, and anchorage-independent growth. These
      results suggested that the excisable retroviral vector may be useful for studying
      the molecular basis for proviral insertion mutagenesis, and that PCPE may play a
      significant role in controlling cell growth and differentiation.

PMID- 9607560
TI  - Transforming growth factor beta is essential for spindle cell conversion of mouse
      skin carcinoma in vivo: implications for tumor invasion.
AB  - Transforming growth factor beta1 (TGF-beta1) regulates both cell growth and
      cellular plasticity and is therefore important in the molecular control of both
      the developmental and neoplastic processes. It has been suggested that TGF-beta1
      may be a positive or negative regulator of tumorigenesis. Stimulation of
      tumorigenesis could be due to its action as an immunosuppressor or as an inducer
      of angiogenesis, or by its direct action on the cell in promoting cellular
      plasticity. In the current study, we provide evidence that TGF-beta1 can act
      directly on keratinocytes in vivo to induce the reversible epithelial-mesenchymal
      conversion of a malignant metastatic keratinocyte cell line. Two squamous clones
      from the cell line were shown to undergo a reversible conversion to a
      fibroblastoid phenotype after culture in 1 ng/ml TGF-beta1. The morphological
      conversion became apparent at 24 h post-TGF-beta treatment and was complete after
      another 24 h. The conversion was characterized by a rapid delocalization of E
      cadherin within 6-12 h posttreatment, followed by down-regulation of E-cadherin
      levels by 72 h. These squamous clones spontaneously converted to a fibroblastoid
      phenotype after s.c. injection in nude mice. Importantly, four of four clones
      that had been stably transfected with a dominant negative TGF-beta type II
      receptor were unable to undergo this mesenchymal switch in vivo, despite the fact
      that all clones stably transfected with neomyocin resistance alone retained their
      spindle characteristics in vivo. This demonstrates that the epithelial
      mesenchymal conversion event is mediated directly via the TGF-beta signaling
      pathway of the tumor cell per se, and that it is sufficient to significantly
      enhance tumorigenicity and the malignant and invasive characteristics of the
      tumor in vivo.

PMID- 9607561
TI  - Redistribution and enhanced protein kinase C-mediated phosphorylation of alpha-
      and gamma-adducin during renal tumor progression.
AB  - Tumor promotion/progression is known to be due in part to increased signaling
      through a variety of mitogenic pathways, including protein kinase C (PKC). To
      determine whether increased PKC activity could play a role in promotion and
      progression of renal cancer, we monitored PKC activity in normal and
      progressively transformed renal neoplasias from Eker rats. Eker rats carry a
      defect in the tumor suppressor TSC2 gene that predisposes them to renal
      carcinoma, whereas additional factors influence tumor promotion/progression in
      accordance with a "two-hit" model. We used the phosphorylation of adducins at Ser
      660, a known PKC phosphorylation site, as a reporter for endogenous PKC activity.
      In normal proximal tubules, total adducin levels (measured with a phosphorylation
      state-insensitive antibody) were relatively high, whereas pSer660-adducin
      (measured with a phosphorylation state-sensitive antibody) levels were very low.
      In comparison, in renal carcinomas, total adducin levels were decreased, and pSer
      660-adducin levels were increased. Changes in phosphorylation correlated with
      changes in localization. In normal tissue, alpha- and gamma-adducin are targeted
      to the apical and basal membranes of proximal tubules, respectively, implying
      unique functions for these related proteins. In early lesions (atypical tubules),
      differential targeting is lost, and both alpha- and gamma-adducins localize to
      the basal membrane. In more advanced lesions, staining in lateral membranes at
      cell-cell contacts becomes apparent. Furthermore, in cells that have lost
      basement membrane contact, plasma membrane targeting is no longer apparent. These
      changes in adducin expression levels, phosphorylation state, and localization
      parallel the increased growth potential and dedifferentiation of the progressive
      tumor phenotypes. These data demonstrate the utility of phosphorylation state
      selective antibodies in immunohistochemical applications as reporters of
      endogenous PKC activity in tissue samples. We also provide the first evidence
      that increased PKC activity and phosphorylation of important target proteins
      occurs during progressive transformation in a non-phorbol ester tumor promotion
      model in vivo.

PMID- 9607562
TI  - Nitric oxide inhibits APO-1/Fas-mediated cell death.
AB  - Activation of the cysteine protease caspases, which are homologous to the product
      of Caenorhabditis elegans cell-death gene ced 3, is required to mediate APO-1/Fas
      induced apoptosis. We report here that nitric oxide (NO) released by exogenous NO
      donors, as well as NO endogenously derived by transfection with the inducible NO
      synthase, substantially suppresses APO-1/Fas-triggered cell death of Jurkat
      cells. The inhibitory NO effect was independent of cGMP, because 8-bromo-cGMP did
      not influence APO-1/Fas-mediated apoptosis. In contrast, NO interferes with the
      APO-1/Fas-induced stimulation of caspases. NO inhibits the proteolytic cleavage
      of caspase-3 (CPP32) into its active subunits, thereby suppressing caspase-3
      activity. In addition, NO potently inhibits apoptosis induction by
      overexpresssion of the death domain protein FADD or the immediate downstream
      target caspase-8. These results suggest that NO modulates the proteolytic cascade
      upstream of caspase-3. Indeed, NO specifically S-nitrosylates caspase-8 and
      caspase-1 and thereby may prevent activation of the proteolytic cascade. The NO
      mediated increase in the resistance toward induction of apoptosis may play a
      major role in mediating immune responses, as well as in the pathogenesis of
      autoimmune diseases.

PMID- 9607563
TI  - Type V collagen is an epithelial cell cycle inhibitor that is induced by and
      mimics the effects of transforming growth factor beta1.
AB  - The regulation of epithelial cell cycle progression by extracellular matrix
      proteins was investigated in mink lung epithelial cells (Mv1Lu cells) and primary
      human keratinocytes. Exogenous type V collagen was able to mimic all of the
      inhibitory effects of type 1 transforming growth factor beta (TGF-beta1). No
      significant inhibitory effect was observed with collagen types I, III, and IV;
      laminin; or fibronectin. The type V collagen used was not contaminated with TGF
      betas. TGF-beta1 increased the rate of type V collagen protein secretion in Mv1Lu
      cells, which occurred coincident with DNA synthesis inhibition. Both TGF-beta1
      and type V collagen inhibited retinoblastoma protein phosphorylation and the
      expression of cyclin-dependent kinase (cdk) 4 and cdk2, but not p27Kip
      expression. Mv1Lu cells constitutively expressing the SV40 T antigen or cdk4 were
      resistant to the inhibitory effects of both TGF-beta1 and type V collagen. Our
      results demonstrate that type V collagen is a novel and specific epithelial cell
      cycle inhibitor and suggest that it may act as an autocrine mediator of the
      inhibitory effects of TGF-beta1.

PMID- 9607564
TI  - There are no bad anticancer agents, only bad clinical trial designs--twenty-first
      Richard and Hinda Rosenthal Foundation Award Lecture.
AB  - Unfortunately, the vast majority (90%) of new anticancer agents designed in the
      laboratory never make it into routine clinical use. The hypothesis of this
      lecture is that many new agents fail in the clinic because the appropriate
      clinical trial(s) that could exploit the attributes of the new agent are not
      performed. An appreciation that both bench and clinical investigations are
      difficult endeavors should aid in improving clinical trial designs and give the
      best chance for new agents to be added to our therapeutic armamentarium.

PMID- 9607565
TI  - New chemotherapeutic agents prolong survival and improve quality of life in non
      small cell lung cancer: a review of the literature and future directions.
AB  - In past years, there has been considerable pessimism over the role of
      chemotherapy in non-small cell lung cancers. The pessimism was largely derived
      from the fact that alkylating agent-based therapies shortened survival and
      produced severe side effects. This was especially important because the vast
      majority of patients (approximately 85%) develop metastatic disease during their
      course. Randomized trials from the 1980s showed that cisplatin-based chemotherapy
      improved patient survival, improved quality of life as assessed by the patients,
      and relieved symptoms in the majority of symptomatic patients. When chemotherapy
      was administered on an outpatient basis, it actually lowered the total patient
      care costs for advanced stage patients. In the 1990s, five new agents, including
      two taxanes (paclitaxel, docetaxel), gemcitabine, navelbine, and irinotecan, were
      shown to produce higher response rates and longer survival in Phase II trials
      compared to cisplatin or carboplatin. In randomized trials, combinations of
      paclitaxel, gemcitabine, and vinorelbine with cisplatin improved the survival of
      advanced stage patients compared to cisplatin alone or in combination with
      etoposide. The toxicity profile of the new agents is also favorable compared to
      cisplatin-based therapy. Preliminary results in earlier stages are also
      encouraging. Thus, currently available chemotherapy given to non-small cell lung
      cancer patients with good performance status can improve survival to a similar
      extent as other solid tumors, such as small cell lung cancer and breast cancer.

PMID- 9607566
TI  - Combined analysis of studies of the effects of the matrix metalloproteinase
      inhibitor marimastat on serum tumor markers in advanced cancer: selection of a
      biologically active and tolerable dose for longer-term studies.
AB  - This combined analysis investigated the effect of marimastat, a specific
      inhibitor of matrix metalloproteinases, on markers of tumor progression measured
      in patients with advanced cancer. By defining the tolerability and biological
      activity of the drug, it aimed to establish an appropriate dose range for use in
      Phase III trials. Patients with advanced, serologically progressive ovarian,
      prostatic, pancreatic, and colorectal cancer were recruited into six
      nonrandomized, dose ranging, multicenter clinical trials in North America and
      Europe. The biological activity of marimastat was assessed by serial measurements
      of the serum tumor markers carcinoembryonic antigen, CA125, CA19-9, and prostate
      specific antigen. Patients were recruited with tumor markers rising by more than
      25% averaged over a 4-week screening period. A biological effect was defined as a
      level of tumor marker at the end of treatment no greater than at study entry; a
      partial biological effect was defined as a rise in the level of tumor marker over
      the treatment period of 0-25% per 4 weeks. Pharmacokinetic and safety data were
      collected and assessed as the studies progressed. All patients were followed up
      for survival.

PMID- 9607567
TI  - High Raf-1 kinase activity protects human tumor cells against paclitaxel-induced
      cytotoxicity.
AB  - Paclitaxel (Taxol) is becoming increasingly important in the treatment of many
      tumors, although a large proportion of tumors fail to respond to this drug. The
      identification of the processes that confer cellular paclitaxel resistance could
      provide potential targets for novel therapies that may help to eliminate
      paclitaxel-resistant tumors. Recent reports suggest that the Raf-1 protein kinase
      may have a profound influence on the level of paclitaxel-induced apoptosis. We
      have critically evaluated the relationship between Raf-1 kinase activity and de
      novo paclitaxel resistance in early-passage human cervical tumors. In the 12 cell
      lines studied, Raf-1 kinase activity was inversely correlated (P = 0.0016) with
      the level of cytotoxicity induced by 60 nM paclitaxel. The relationship between
      these two parameters seems to be more than an epiphenomenon, because genetic down
      regulation of Raf-1 kinase activity led to an approximately 4-fold increase in
      paclitaxel-induced cytotoxicity. The data from both our transfection studies and
      those on the 12 unperturbed cell lines are consistent with Raf-1 kinase being a
      negative determinant of paclitaxel-induced cytotoxicity. Because the cytotoxicity
      of paclitaxel is primarily attributable to apoptosis, these data suggest that Raf
      1 kinase acts to suppress paclitaxel-induced apoptosis. These data suggest that
      the clinical effectiveness of paclitaxel could be substantially improved by the
      use of Raf-1 kinase inhibitors, provided that a similar relationship between Raf
      1 kinase activity and paclitaxel cytotoxicity exists in the clinic, especially in
      those tumor sites where paclitaxel is the current treatment of choice e.g.,
      ovarian and breast cancer.

PMID- 9607568
TI  - Antibody responses in melanoma patients immunized with an anti-idiotype antibody
      mimicking disialoganglioside GD2.
AB  - We initiated a clinical trial for patients with advanced malignant melanoma
      treated with an anti-idiotype antibody that mimics the disialoganglioside GD2. We
      report the clinical and immune responses of the first 12 patients entered into
      this trial. Patients received 1-, 2-, 4-, or 8-mg doses of the anti-idiotype
      antibody mixed with 100 microg of QS-21 adjuvant every other week, four times,
      and then monthly. Twelve patients have been on trial for 2-23 months, and all of
      them have generated immune responses. Patients were removed from the study if
      they demonstrated disease progression. Hyperimmune sera from all 12 patients
      revealed an anti-anti-idiotypic Ab3 response, as demonstrated by the inhibition
      of Ab2 binding to Ab1 by patients' immune sera. To further test the anti-anti
      idiotypic response, patients' Ab3 antibodies were affinity purified on Sepharose
      4B columns containing adsorbed immunizing anti-idiotype immunoglobulin. Purified
      Ab3 of all patients studied inhibited binding of Ab1 to a GD2-positive cell line.
      Purified Ab3 also inhibited binding of Ab1 to purified GD2, in a manner
      comparable to equal quantities of purified Ab1. The patient Ab3 was truly an Ab1'
      because it specifically bound to purified disialoganglioside GD2. The isotypic
      specificity of the Ab3 antibody was predominantly IgG, with only minimal IgM. The
      predominant IgG subclass was IgG1, with approximately equal quantities of IgG2,
      IgG3, and IgG4. These Ab3 antibodies reacted specifically with tumor cells
      expressing GD2 by immune flow cytometry and immunoperoxidase assays. Five
      patients' Ab3 antibodies studied for antibody-dependent cellular cytotoxicity
      were positive. One patient had a complete clinical response, with resolution of
      soft tissue disease, and six patients had stable disease, ranging from 9 to 23
      months, and are being continued on vaccine therapy. Toxicity consisted of local
      reaction at the site of the injection, including induration and pain that
      generally resolved within a few days. Mild fever and chills were observed in 75%
      of the patients but rarely required acetaminophen. There was no additional
      toxicity, including abdominal pain that was previously seen with infusion of
      murine monoclonal anti-GD2 antibody. Current trials include patients with stage
      III melanoma and small cell lung cancer. Future trials will attempt to enhance
      the antitumor response by the addition of interleukin 2, granulocyte macrophage
      colony-stimulating factor, and other cytokines, together with the 1A7 vaccine.

PMID- 9607569
TI  - In vivo toxicity, pharmacokinetics, and anticancer activity of Genistein linked
      to recombinant human epidermal growth factor.
AB  - Epidermal growth factor receptor (EGFR)-associated protein tyrosine kinase (PTK)
      complexes have vital anti-apoptotic functions in human breast cancer cells. We
      have shown previously that targeting the naturally occurring PTK inhibitor
      genistein to the EGFR-associated PTK complexes using the EGF-Genistein (Gen)
      conjugate triggers rapid apoptotic cell death in human breast cancer cells and
      abrogates their in vitro clonogenic growth. In the present study, we examined the
      in vivo toxicity profile, pharmacokinetics, and anticancer activity of EGF-Gen.
      No toxicities were observed in mice treated with EGF-Gen at dose levels as high
      as 40 mg/kg administered i.p. as a single dose or 140 mg/kg administered i.p.
      over 28 consecutive days. EGF-Gen significantly improved tumor-free survival in a
      severe combined immune deficiency (SCID) mouse xenograft model of human breast
      cancer, when it was administered 24 h after inoculation of tumor cells. At 100
      microg/kg/day x 10 days (1 mg/kg total dose), which is >100-fold less than the
      highest tested and nontoxic cumulative dose (ie., 140 mg/kg) in mice, EGF-Gen was
      more effective than cyclophosphamide (50 mg/kg/day x 2 days), Adriamycin (2.5
      mg/kg x 1 day), or methotrexate (0.5 mg/kg x 1 day), the most widely used
      standard chemotherapeutic drugs for breast cancer, and resulted in 60% long-term
      tumor-free survival. Furthermore, treating SCID mice with established s.c. human
      breast cancer xenografts of 0.5-cm diameter with EGF-Gen at this dose level
      resulted in disappearance of the tumors in two of five mice and >50% shrinkage in
      three of five mice within 10 days, whereas all of the control tumors in five PBS
      treated mice as well as five mice treated with unconjugated Gen (1 mg/kg/day x 10
      days) showed >200% increase in diameter during the same observation period. EGF
      Gen treatment reduced the growth rate of breast cancer xenografts of 1.0-cm
      diameter, but unlike with tumors of 0.5-cm diameter, it failed to cause shrinkage
      or disappearance of these larger tumors. The level of EGF-Gen systemic exposure
      that was effective in SCID mice was achieved in cynomolgus monkeys without any
      significant side effects detectable by clinical observation, laboratory studies,
      or histopathological examination of multiple organs. EGF-Gen might be useful in
      the treatment of breast cancer as well as other EGFR-positive malignancies.

PMID- 9607570
TI  - Human tumor antigen-specific T lymphocytes and interleukin-2-activated natural
      killer cells: comparisons of antitumor effects in vitro and in vivo.
AB  - Human antitumor effector cells include class I major histocompatibility complex
      (MHC)-restricted T cells and non-MHC-restricted natural killer (NK) cells. These
      two types of effector cells have not been directly compared for the ability to
      eliminate tumor cell targets. Here, we compare in vitro and in vivo antitumor
      functions of two human T-cell lines specific for a shared tumor antigen to the
      antitumor functions of A-NK cells, a subset of IL-2-activated NK cells. Human
      squamous cell carcinoma of the head and neck cell lines cultured in suspensions
      or as spheroids or tumor xenografts established in nude mice were used to
      evaluate antitumor functions of IL-2-activated and expanded T and NK effector
      cells in various assays, both in vitro and in vivo. Both tumor cell targets, PCI
      13 and OSC-19, expressed class I and II MHC antigens after IFN-gamma
      pretreatment, gave rise to tumors upon injection into immunosuppressed nude mice,
      and were resistant to lysis by resting NK cells but sensitive to lysis mediated
      by A-NK cells or HLA-A2-restricted T-cell lines specific for a shared squamous
      cell carcinoma of the head and neck antigen. No significant differences were
      observed in the ability of A-NK cells or tumor-specific T cells to bind to tumor
      cell monolayers or to enter into spheroids. However, A-NK cells mediated
      significantly higher killing than tumor-specific CD8+ T cells in 4-h 51Cr-release
      assays (a measure of cell membrane damage and necrosis), 1-h [3H]thymidine
      release assays (a measure of DNA fragmentation and apoptosis), and in terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling assays (a measure of
      apoptosis). In contrast, CD8+ T cells were consistently more effective than A-NK
      cells in inducing growth inhibition of tumor cells in 24-h MTT assays. In the
      presence of tumor-specific antibodies, A-NK cell binding, entry into spheroids,
      and infiltration into tumor in vivo were significantly increased. In vivo
      perilesional delivery of effector cells to mice with established tumors indicated
      that human A-NK cells exert antitumor effects as potent as those of tumor
      specific T cells. However, in contrast to tumor-specific T cells, A-NK cells are
      readily available for cancer therapy, expand rapidly in culture without prior
      sensitization, and can be armed with antitumor antibodies to increase
      localization of effector cells to the tumor.

PMID- 9607571
TI  - Infrequent expression of p21 is related to altered p53 protein in pancreatic
      carcinoma.
AB  - This study is designed to investigate the expression of p21 and its relation to
      altered p53 protein in pancreatic carcinoma (PC). Immunohistochemical staining of
      formalin-fixed, paraffin-embedded tissue sections of PC was performed using a
      monoclonal antibody against p21 (187), with a parallel examination of altered p53
      protein. The expression of p21 was only found in 12 of 58 (20.7%) PCs and,
      moreover, was mainly restricted to the well-differentiated ductal epithelium.
      Sixty-four % (37 of 58) of PCs showed positive p53 staining, and this change was
      significantly related to the absence of p21 expression (P < 0.01). In a subgroup,
      the proportion of the undetectable p21 expression and the expression of p53 were
      increased with increasing tumor grade but decreased with advancing clinical
      stage. The results of the present study suggest that the absence of p21
      expression is very common in PCs and appears to relate to altered p53 protein.
      Moreover, the abnormalities involving the expression of p21 and p53 may play a
      more important role in the development than in the progression of this
      malignancy.

PMID- 9607572
TI  - Oral topotecan given once or twice daily for ten days: a phase I pharmacology
      study in adult patients with solid tumors.
AB  - Prolonged exposure to topotecan (TPT) in in vitro experiments and in vivo studies
      in animals yielded the highest antitumor efficacy. An oral bioavailability of TPT
      of 32-44% enables convenient prolonged administration. Because of unpredictable
      diarrhea in the third week of the twice daily (b.i.d.) 21-day schedule of p.o.
      administered TPT and the finding of optimal down-regulation of topoisomerase I
      level after 10-14 days in mononuclear peripheral blood cells, a shorter period of
      administration (10 days) was chosen for Phase I and pharmacological studies of
      oral administration of TPT. Adult patients with malignant solid tumors that were
      refractory to standard forms of chemotherapy were entered. Two dose schedules
      were studied: once daily (o.d.) and b.i.d. administration for 10 days every 3
      weeks. TPT o.d. for 10 days was studied at dose levels 1.0, 1.4, and 1.6
      mg/m2/day, and dose levels were 0.5, 0.6, 0.7, and 0.8 mg/m2 with the 10-day
      b.i.d. schedule. Pharmacokinetics were performed on days 1 and 8 of the first
      course using a validated high-performance liquid chromatographic assay and
      noncompartmental pharmacokinetic methods. Nineteen patients were entered in the
      10-day o.d. schedule, with a total of 48 courses given. Dose-limiting toxicity
      (DLT) was reached at 1.6 mg/m2/day and consisted of common toxicity criteria
      (CTC) grade IV thrombocytopenia and CTC grade III diarrhea. The maximum tolerated
      dose was 1.4 mg/m2/day. In the 10-day b.i.d. administration of TPT, a total of 64
      courses were studied in 20 patients. DLT was reached at a dose of 0.8 mg/m2
      b.i.d. and consisted of CTC grade IV myelosuppression and CTC grade IV diarrhea.
      The maximum tolerated dose was 0.7 mg/m2 b.i.d. Nonhematological toxicities with
      both schedules included mild nausea and vomiting, fatigue, and anorexia.
      Pharmacokinetics revealed a substantial variation of the area under the plasma
      concentration-time curve of TPT lactone in both schedules. Significant
      correlations were observed between the myelotoxicity parameters and the area
      under the plasma concentration-time curve at day 1 of TPT lactone o.d. and b.i.d.
      The DLT of 10 daily administrations of oral topotecan every 3 weeks consisted of
      a combination of myelosuppression and diarrhea for both schedules studied. The
      recommended doses for Phase II studies are 1.4 mg/m2/day for 10 days for the o.d.
      administration and 0.7 mg/m2 for the b.i.d. schedule.

PMID- 9607573
TI  - Phase I clinical trial of perillyl alcohol administered daily.
AB  - Perillyl alcohol (POH; NSC-641066), a naturally occurring monoterpene, has shown
      antitumor and preventive activity in preclinical studies in rodent models. Drug
      related activities that have been observed include the induction of apoptosis,
      cell cycle arrest, the inhibition of posttranslational modification of proteins
      that are involved in signal transduction, and differential gene regulation. We
      treated 18 patients who had advanced malignancies with POH, which was given on a
      continuous three-times-a-day schedule at the following doses: (a) level 1 (L1),
      800 mg/m2/dose; (b) level 2 (L2), 1600 mg/m2/dose; and (c) level 3 (L3), 2400
      mg/m2/dose. The main toxicity, which seemed to be dose related, was
      gastrointestinal and included nausea and vomiting, anorexia, unpleasant taste,
      satiety, and eructation. Two heavily pretreated ovarian cancer patients
      experienced reversible > or =grade 3 granulocytopenia. Grade 1-2 fatigue was also
      noted. The parent drug was not detectable in the plasma. The mean peak plasma
      levels of the two main metabolites on days 1 and 29 were 175 and 139 microM (L1),
      472 and 311 microM (L2), and 456 and 257 microM (L3) for perillic acid (PA) and
      7.1 and 9.8 microM (L1), 34.2 and 34.0 microM (L2), and 26.2 and 23.4 microM (L3)
      for dihydroperillic acid (DHPA). Peak levels were noted 2-3 h postingestion for
      PA and 3-5 h postingestion for DHPA. Metabolite half-lives measured about 2 h for
      each. POH, PA, and DHPA were detectable in the urine of all patients at L3. About
      9% of the total dose was recovered in the first 24 h. The majority was recovered
      as PA; less than 1% was recovered as POH. Disease stabilization for > or =6
      months was seen, although no objective tumor responses were noted. Further study
      of POH continues with a more frequent dosing schedule.

PMID- 9607574
TI  - Phase I clinical and pharmacological studies of benzylacyclouridine, a uridine
      phosphorylase inhibitor.
AB  - Benzylacyclouridine (BAU, IND 039655) is a potent and specific inhibitor of
      uridine phosphorylase (UrdPase; EC 2.4.2.3). This enzyme plays a major role in
      regulating uridine homeostasis and also catalyzes the conversion of
      fluoropyrimidine nucleosides to their respective bases. Inhibition of UrdPase
      enzyme activity 18-24 h after 5-fluorouracil (5-FU) administration increased
      plasma levels of uridine and enhanced the therapeutic index of 5-FU by rescuing
      normal tissues. Moreover, in vitro preclinical studies have also shown that
      inhibiting UrdPase enzyme activity by BAU prior to administration of 5-FU
      increased cytotoxicity in a number of human cancer cell lines. A series of
      preclinical studies was performed in dogs and pigs to evaluate the
      pharmacological and pharmacodynamic properties of BAU. These data showed a
      sustained elevation in plasma uridine concentration in both animal models. The
      rapid degradation of a tracer dose of uridine into uracil was virtually arrested
      by BAU administered both p.o. or i.v. The t1/2 of BAU was 1.8-3.6 h in dogs, with
      bioavailability levels of 85% (30 mg/kg) and 42.5% (120 mg/kg). In pigs, the half
      life varied from 1.6 to 2.3 h, with a bioavailability of 40% at 120 mg/kg. The
      drug was distributed into most tissues with a tissue: plasma ratio of
      approximately 0.7. On the basis of these preclinical studies, we performed a
      Phase I clinical trial of BAU in patients with advanced cancer. Patients received
      200, 400, 800, and 1600 mg/m2 BAU as a single oral dose. Toxicities included
      grade 2 anemia, grade 1 fever, grade 1 fatigue, grade 1 constipation, and grade 1
      elevation in alkaline phosphatase; none of these toxicities were observed to be
      dose dependent. The maximum tolerated dose and dose-limiting toxicity were not
      reached at the doses given. BAU plasma concentrations and area under the curve
      correlated linearly with the oral dose level. The pharmacokinetics of BAU were
      consistent with a first-order clearance, with average peak concentrations ranging
      from 19 microM (200 mg/m2) to 99 microM (1600 mg/m2) and tbeta1/2 ranging from
      3.0 to 3.9 h at the four dose levels. Compared with baseline plasma uridine,
      treatment of patients with 200, 400, 800, and 1600 mg/m2 BAU increased peak
      uridine concentrations by 120, 150, 250, and 175%, respectively. On the basis of
      this clinical study, the suggested Phase II starting dose of BAU in combination
      with 5-FU is 800 mg/m2. Studies combining BAU with 5-FU and incorporating
      appropriate molecular and biochemical end points to assess the effects of this
      drug combination on tumor and/or surrogate tumor tissue are under way.

PMID- 9607575
TI  - In vivo native cellular fluorescence and histological characteristics of head and
      neck cancer.
AB  - Native cellular fluorescence (NCF) represents the innate capacity of tissues to
      absorb and emit light of a specified wavelength. The ability to define the
      relationship of in vivo NCF with biological characteristics of neoplastic disease
      may allow for an improved understanding of the clinical course of disease. Head
      and neck cancers from 35 patients were evaluated in vivo for NCF characteristics
      using a xenon lamp-based spectrometer coupled to a handheld fiberoptic probe.
      Spectral assessment was limited to lambda 450-nm emission characteristics, in
      which tissues were excited at various wavelengths, ranging from lambda 290 nm to
      lambda 415 nm, and the intensity of lambda 450 nm emission was recorded. Each
      cancer was subsequently biopsied and assessed for histological differentiation by
      a pathologist who was blinded to NCF analysis. Considerable variation in spectral
      characteristics between head and neck cancers was identified, which was
      determined, in part, by NCF characteristics of the normal mucosa from the same
      patient. Poorly differentiated tumors were more likely than well- or moderately
      differentiated tumors to have lower excitation maxima (P < 0.05 by ANOVA). Most
      significantly, the tumor differentiation status, as well as the probability of
      demonstrating recurrent disease, could also be related to the NCF characteristics
      of the patient's normal mucosa from the same site within the upper aerodigestive
      tract. NCF analysis may represent an effective tool to identify biological
      characteristics of head and neck tumors in vivo without the need for invasive
      biopsies. Results suggest the need to explore the determinants of NCF
      characteristics expressed by clinically normal mucosa.

PMID- 9607576
TI  - Phase I trial of subcutaneous recombinant human interleukin-12 in patients with
      advanced renal cell carcinoma.
AB  - Patients with advanced renal cell carcinoma were treated in a Phase I trial with
      escalating doses of recombinant human interleukin-12 (rHuIL-12) given on days 1,
      8, and 15 of each 28-day cycle. Treatment in the initial dose scheme consisted of
      a fixed dose with dose levels of 0.1, 0.5, and 1.0 microg/kg given to cohorts
      composed of three or six patients. On the basis of the toxicity profile, a second
      scheme (up-titration) was undertaken wherein rHuIL-12 was escalated for each
      patient from week 1 to week 2, to a target dose given week 3 and thereafter;
      cohort target dose levels were 0.5, 0.75, 1.0, 1.25, and 1.5 microg/kg. Fifty-one
      patients were treated: 32 (63%) had prior cytokine therapy and 19 (37%) had
      received no prior systemic therapy. The maximum tolerated dose for the fixed dose
      scheme was 1.0 microg/kg. Dose-limiting toxicities included increase in
      transaminase concentration, pulmonary toxicity, and leukopenia. The most severe
      toxicities occurred with the first injection and were milder upon further
      treatment. With the up-titration dose scheme, the maximum tolerated dose was
      reached at 1.5 microg/kg, and dose-limiting toxicity consisted of an increase in
      serum transaminase levels. At the maximum tolerated dose of 1.5 microg/kg, serum
      IL-12 levels increased to a mean peak level of 706 pg/ml. Serum levels of IFN
      gamma increased to a mean peak level of about 200 pg/ml at 24 h after the first
      maintenance dose of 1.5 microg/kg. The best responses were as follows: one
      patient had complete response, 34 patients were stable, 14 patients showed
      progression, and 1 patient was inevaluable. In conclusion, rHuIL-12 was
      relatively well tolerated when administered by s.c. injection. The recommended
      dose according to the up-titration schedule of rHuIL-12 (microg/kg) for Phase II
      trials was as follows: cycle 1, 0.1 (day 1), 0.5 (day 8), 1.25 (day 15); cycle 2
      onwards, 1.25. Phase II trials of rHuIL-12 were initiated in previously untreated
      patients with renal cell carcinoma and in patients with melanoma.

PMID- 9607577
TI  - Phase I study of suramin combined with doxorubicin in the treatment of androgen
      independent prostate cancer.
AB  - In this study, we determined the maximum tolerated plasma concentration of
      suramin (within the predetermined study target range) when combined with
      doxorubicin in the treatment of androgen-independent prostate cancer. Twenty-four
      patients received suramin dosages based on proportional adjustment of the steady
      state plasma suramin concentration to achieve the targeted plasma concentrations
      of 50-100, 101-150, 151-200, or 201-250 microg/ml. Doxorubicin (20 mg/m2) was
      administered i.v. over 24 h at weekly intervals. Suramin was given i.v. over 2 h
      twice weekly. Patients received treatment until dose-limiting toxicity or disease
      progression. Side effects similar to those reported for suramin and doxorubicin
      administered as individual agents were observed. Dose-limiting motor neuropathy
      developed in three patients (13%). Twelve of 24 evaluable patients (50%; 95%
      confidence interval, 28-71%) and 6 of 10 evaluable patients (60%; 95% confidence
      interval, 26-88%) had a >50% decrease of prostate-specific antigen and measurable
      lesions, respectively. The maximum tolerated plasma level of suramin when
      combined with doxorubicin was 151-200 microg/ml. Future studies on suramin
      combined with doxorubicin or other agents could be performed using a fixed dosing
      scheme with a targeted suramin steady-state plasma concentration of 200
      microg/ml.

PMID- 9607579
TI  - Quantitative [F-18]fluorodeoxyglucose positron emission tomography in
      pretreatment and grading of sarcoma.
AB  - The purpose of this study was to determine the relationship between sarcoma tumor
      grade and the quantitative tumor metabolism value for [F-18]fluorodeoxyglucose
      (FDG) determined by positron emission tomography (PET) imaging. Seventy patients
      with bone or soft-tissue sarcomas underwent PET scanning with quantitative
      determination of tumor FDG metabolic rate (MRFDG) before treatment. MRFDG
      (micromol/g/min) for each tumor was compared with National Cancer Institute tumor
      grade, S-phase percentage, and percentage of aneuploidy of the tumor population.
      The pretreatment quantitative determination of tumor MRFDG by PET correlates
      strongly with tumor grade but not with the other selected histopathological tumor
      correlates. In addition, overlap of MRFDG PET values with tumor grade suggests
      that PET, an objective tumor measurement, may provide an alternative means of
      assessing tumor biological potential or may have the potential to overcome some
      of the limitations of traditional pathological evaluation. FDG PET can uniquely
      provide a metabolic profile of a diverse group of sarcomas noninvasively and
      provide clinically relevant tumor biological information.

PMID- 9607578
TI  - A two-part phase I trial of high-dose interleukin 2 in combination with soluble
      (Chinese hamster ovary) interleukin 1 receptor.
AB  - Our purpose was to determine the maximum tolerated dose and toxicity associated
      with soluble Chinese hamster ovary [s(CHO)] recombinant human interleukin (IL) 1
      receptor (IL-1R; Immunex, Seattle, WA) administration in humans and to determine
      the effective biological dose and/or maximum tolerated dose of the s(CHO) IL-1R
      in combination with high-dose IL-2 as determined by reduction in IL-2 toxicity
      and modulation of its biological effects. Twenty-seven patients with metastatic
      cancer were treated with escalating doses of s(CHO) IL-1R at 1, 1, 5, 10, 20, 40,
      and 55 mg/m2 i.v. on days -6 (except cohort 2), 1, and 15 and IL-2 at doses of
      300,000 IU/kg (cohort 1) and 600,000 IU/kg (cohorts 2-7) i.v. every 8 h on days 1
      5 and 15-19. No toxicity directly attributable to s(CHO) IL-1R was observed. The
      median number of IL-2 doses was 23. Hypotension and neurotoxicity were the major
      dose-limiting toxicities for the IL-2/s(CHO) IL-1R combination. Of the 24
      patients treated with full-dose IL-2, there were six responses, three complete
      and three partial (response rate, 25%). Three patients developed thyroid
      dysfunction, and all 3 responding melanoma patients exhibited vitiligo. The t1/2
      of s(CHO) IL-1R alone was 24-30 h and was not significantly altered by
      coadministration with IL-2. Whole-blood functional assays indicated that
      sufficient s(CHO) IL-1R was present in the circulation at top dose levels to
      inhibit the in vitro effects of IL-1beta on IL-8 induction; however, no effect on
      IL-2-induced IL-8 induction, or on the IL-1beta- or IL-2-induced tumor necrosis
      factor production, was observed. Suppression of IL-2-mediated tumor necrosis
      factor alpha and IL-6 induction in vivo during the first 24 h after IL-2
      administration was observed, and the neutrophil chemotactic defect normally seen
      with IL-2 was not observed. IL-1R antagonist induction far exceeded that seen
      previously with IL-2 alone. No inhibition of either serum C-reactive protein
      induction or enhanced urinary nitrate excretion and no consistent effect on IL-2
      related changes in peripheral blood mononuclear cell phenotype or endothelial
      adhesion molecule expression were seen. The coadministration of s(CHO) IL-1R
      produced no apparent reduction in IL-2 clinical toxicity manifested by either the
      ability to administer more IL-2 than anticipated or a reduction in the toxicity
      associated with a given amount of IL-2. Therefore, no effective biological dose
      could be identified for the s(CHO) IL-1R.

PMID- 9607580
TI  - Evaluation of the balance between angiogenic and antiangiogenic circulating
      factors in patients with breast and gastrointestinal cancers.
AB  - Angiogenesis is a critical determinant of tumor growth. Tumor cells produce or
      induce angiogenic molecules that act specifically on endothelial cells (ECs) but
      also release angiostatic molecules. Thus, tumor angiogenesis represents a net
      balance between positive and negative regulators of neovascularization. Sera from
      patients with breast or gastrointestinal cancers were evaluated for their
      capacity to selectively modulate the proliferation of human umbilical vein ECs;
      sera from 15 of 78 (19%) breast cancer patients and 8 of 53 (15%)
      gastrointestinal cancer patients induced human umbilical vein EC growth, whereas
      sera from 4 of 78 (5%) breast cancer patients and 1 of 53 (2%) gastrointestinal
      cancer patients inhibited EC proliferation. Growth-stimulatory sera were
      significantly more frequent among postmenopausal (14 of 53) than premenopausal (1
      of 25) breast cancer patients; inhibitory activity was observed in 3 of 25
      premenopausal patients versus 1 of 53 postmenopausal individuals. The half-life
      of serum-stimulating and -inhibiting factors seemed to differ, because
      stimulatory activity but not inhibitory activity was decreased at 5 days after
      surgery. The levels of vascular endothelial growth factor were elevated in about
      45% of patients with growth-stimulatory sera, whereas the serum inhibition of EC
      growth was found to be due, at least in part, to high levels of soluble
      thrombospondin.

PMID- 9607581
TI  - p53 and thymidylate synthase expression in untreated stage II colon cancer:
      associations with recurrence, survival, and site.
AB  - We initiated a retrospective study to determine whether p53 status and
      thymidylate synthase (TS) protein expression in primary colon tumors influence
      recurrence and survival for patients with stage II colon cancer. Tumor specimens
      from 45 consecutive untreated patients with stage II colon cancer were examined
      for p53 and TS protein expression using immunohistochemistry. The median follow
      up was 5.1 years. Eighteen patients had left-sided tumors, and 27 had right-sided
      tumors. Fourteen of 45 patients (31%) developed recurrence. p53 overexpression
      was detected in the tumors of 18 patients (40%); 10 patients (55%) with p53
      overexpression recurred; and 4 of 27 (15%) without evidence of p53 overexpression
      recurred (P = 0.002). High TS expression was detected in the tumors of 16
      patients (36%): 8 patients (50%) with high TS expression recurred, and 6 patients
      (21%) with low TS expression recurred (P = 0.027). Patients with p53
      overexpression had a significantly poorer survival than did those patients
      without p53 overexpression (P < 0.001). High TS expression was associated with
      poor survival (P = 0.004). p53 overexpression and high TS expression were
      significantly associated with left-sided tumors (P = 0.003 and P = 0.022).
      Thirteen of 16 patients (81%) with high TS expression also overexpressed p53, and
      24 of 29 patients (81%) with low TS expression did not manifest p53
      overexpression (P < 0.001). p53 and TS expression in primary stage II colon
      cancer are associated and appear to influence recurrence and survival. In this
      pilot study, left-sided tumors demonstrate significantly more p53 overexpression
      and significantly higher TS expression than do right-sided tumors, which may
      explain the significantly poorer survival for patients with left-sided tumors.

PMID- 9607582
TI  - Patients with isolated trisomy 8 in acute myeloid leukemia are not cured with
      cytarabine-based chemotherapy: results from Cancer and Leukemia Group B 8461.
AB  - To date, neither the clinical significance of isolated trisomy 8, the most
      frequent trisomy in acute myeloid leukemia (AML), nor the effect of age within a
      single cytogenetic group has been examined. We report a large cohort of adult
      trisomy 8 patients and examine whether increasing age within a homogeneous
      cytogenetic group alters clinical outcome. Characteristics and outcome of
      patients with isolated trisomy 8 enrolled in the prospective Cancer and Leukemia
      Group B (CALGB) cytogenetic study CALGB 8461 are described. Isolated trisomy 8
      was identified in 42 (3.03%) of 1387 patients enrolled in five CALGB treatment
      protocols. These patients had a median age of 64 (range, 16-79) years, 50% female
      proportion, and a low frequency of hepatomegaly (10%) or splenomegaly (10%).
      Laboratory features included a median white blood count of 7.3 x 10(9)/L,
      nonspecific French-American-British distribution, with 36% of patients having
      Auer rods. Treatment outcome was unsatisfactory with a complete remission (CR)
      rate of 59%, median CR duration of 13.6 months, and median survival of 13.1
      months. Older age adversely affected outcome; trisomy 8 patients > or =60 years
      had both an inferior CR rate (40% versus 88%; P = 0.004) and overall survival
      (median, 4.8 versus 17.5 months; P = 0.01), as compared with those <60 years of
      age. Of the patients <60 years of age, only four remain alive, and all received
      noncytarabine-based intensive chemotherapy, followed in three cases by autologous
      (n = 2) or allogeneic (n = 1) stem cell transplant in CR1. Adults with AML and
      isolated trisomy 8 have a poor outcome that is accentuated by increasing age and
      is rarely cured with cytarabine-based therapy. Alternative investigational
      treatments should be considered for individuals with this AML subset.

PMID- 9607583
TI  - p53 point mutations and thymidylate synthase messenger RNA levels in disseminated
      colorectal cancer: an analysis of response and survival.
AB  - Recent studies suggest that there may be a strong correlation between the p53
      status of a tumor and a patient's response to chemotherapy. Therefore, we
      determined p53 status in 36 patients with disseminated colorectal cancer by cDNA
      sequencing and immunohistochemical staining, as well as by the gene expression
      level of thymidylate synthase (TS), the target enzyme of 5-fluorouracil (5-FU),
      by reverse transcription-PCR. Ten patients (28%) experienced a clinical response
      to 5-FU chemotherapy. Overall, TS expression and response to chemotherapy were
      associated: 9 of 18 (50%) patients with TS < or = 3.0 x 10(-3) responded,
      compared to 1 of 18 (6%) patients with TS > 3.0 x 10(-3) (P = 0.003). p53
      mutations were found in 21 of 36 patients (58%) using cDNA cycle sequencing, and
      p53 protein overexpression was found in 20 of 32 patients (62%) using
      immunohistochemistry staining. Overall p53 status and response to chemotherapy
      were associated: 5 of 10 (50%) patients with wild-type p53 or negative p53
      staining experienced a response, but only 5 of 26 (19%) patients with mutant p53
      or p53 overexpression responded. TS expression, but not expression of p53, was
      significantly associated with overall survival (P = 0.002). Patients with wild
      type p53 had significantly lower TS levels compared to patients with mutated p53
      (P = 0.044). In this study, we also present data linking specific p53 point
      mutations to TS expression levels and resistance to 5-FU. Although the number of
      patients is relatively small, these results identify p53 status and TS gene
      expression as associated with response in disseminated colorectal cancer;
      independent studies are needed to confirm these findings and to provide
      information leading to a better understanding of the role of 5-FU-based
      chemotherapy in the treatment of colorectal cancer.

PMID- 9607584
TI  - Loss of p21WAF1/Cip1 protein expression accompanies progression of sporadic
      colorectal neoplasms but not hereditary nonpolyposis colorectal cancers.
AB  - p21 (p21WAF1/Cip1), a cyclin-dependent kinase inhibitor, induces G1 arrest and
      can inhibit the activity of the proliferating cell nuclear antigen (PCNA). We
      analyzed p21 expression during colorectal tumorigenesis, its association with its
      transcriptional regulator p53, and its relationship to rates of cell
      proliferation and apoptosis. p21 and p53 protein expression were examined in
      sporadic tumors and hereditary nonpolyposis colorectal cancers (HNPCCs) by
      immunohistochemistry (IHC) and immunoblotting. Apoptosis was examined using a DNA
      nick end-labeling assay, and cell proliferation was examined by PCNA staining. In
      normal colorectal epithelia, nuclear p21 staining was uniformly detected in crypt
      cells of the superficial compartment (upper one-third) that stained negatively
      for PCNA. p21 and PCNA expression were, therefore, mutually exclusive. In
      sporadic cases, a decrease in the frequency of p21 expression accompanied adenoma
      development and progression to carcinoma. Specifically, p21 was detected in 12 of
      16 (75%) adenomas and 10 of 32 (31%) carcinomas. In contrast to sporadic cases,
      HNPCCs with known mutations in DNA mismatch repair genes expressed p21 in 12 of
      15 (80%) carcinomas. An inverse relationship between p21 and p53 was observed
      wherein mutant p53 proteins were detected in 4 of 15 (27%) HNPCCs versus 22 of 32
      (69%) sporadic carcinomas. Although p21+ carcinoma cells were generally negative
      for p53, IHC revealed that some carcinoma cells expressed both p21 and p53
      proteins. Furthermore, p53-mutated SW480 colon carcinoma cells were found to
      coexpress p21 and p53, suggesting that p21 can also be activated by a p53
      independent mechanism. No association was found between p21 or PCNA and apoptotic
      labeling indices in adenomas or carcinomas. In conclusion, a decrease in p21
      expression accompanies neoplastic progression in sporadic cases but not in
      HNPCCs. This finding appears related to p53 status in that the frequency of p53
      expression was significantly reduced in HNPCCs compared to sporadic cases,
      suggesting a difference in their molecular pathways of tumorigenesis.

PMID- 9607585
TI  - Heat shock proteins hsp27 and hsp70: lack of correlation with response to
      tamoxifen and clinical course of disease in estrogen receptor-positive metastatic
      breast cancer (a Southwest Oncology Group Study).
AB  - In this study, we tested the hypothesis that heat shock proteins (hsps) 27 and 70
      are associated with clinical resistance to tamoxifen. hsp27 is, like progesterone
      receptor, an estrogen-regulated protein. hsp70 is also of interest because of its
      interaction with estrogen receptors and because hsp70 is a component of the
      molecular chaperone machinery functioning in the assembly and trafficking of
      steroid receptors. In addition, hsps in general help protect cells against
      noxious stimuli and stress, and their expression has been linked to drug
      resistance. The study involved 205 tumors from estrogen receptor-positive
      tamoxifen-treated breast cancer patients with metastatic disease. All patients
      received daily tamoxifen as initial therapy for metastatic disease. The study
      began in 1982, and follow-up is now 9 years. hsp27 and hsp70 were detected by
      immunohistochemistry and scored according to the nuclear and/or cytoplasmic
      content. Expression of hsp27 or hsp70 was unrelated to estrogen receptor content,
      progesterone receptor content, menopausal status, age, and presence of visceral
      disease. Cytoplasmic and nuclear hsp27 positivities were weakly and inversely
      related to each other (P = 0.05). There was a significant association between
      cytoplasmic hsp27 and cytoplasmic hsp70 content (P < 0.001), as well as between
      nuclear hsp70 and nuclear hsp27 content (P = 0.001). Cytoplasmic and nuclear
      hsp70 were also associated (P = 0.02). However, increased hsp27 and hsp70
      expression (nuclear or cytoplasmic) was not significantly associated with
      response to tamoxifen, time to treatment failure, or survival. Thus, this study
      clarifies the lack of clinical utility of hsp27 and hsp70 in predicting the
      response to tamoxifen in an estrogen receptor-positive breast cancer population.

PMID- 9607586
TI  - Biomarker study of primary nonmetastatic versus metastatic invasive bladder
      cancer. National Cancer Institute Bladder Tumor Marker Network.
AB  - A cohort of 109 patients with primary transitional cell carcinomas, stages T2-T3,
      grade 2 or higher, was identified and further divided into two groups based on
      lymphatic metastasis at the time of cystectomy (n = 57 cases) or absence of
      detectable metastatic disease over a minimum of 5 years of follow-up after
      cystectomy (n = 52). Blocks corresponding to the primary tumor lesions were
      sectioned and distributed to different laboratories to be analyzed.
      Immunohistochemistry on deparaffinized tissue sections was conducted for
      evaluation of p53 nuclear overexpression (monoclonal antibody PAb1801),
      assessment of proliferative index (Ki-67 antigen-monoclonal antibody MIB1), and
      microvascular counts (factor VIII-related antigen). DNA content/ploidy studies
      were performed on material obtained from thick sections. A double-blinded
      strategy was used for the evaluation of laboratory data versus clinical
      parameters. The cutoff value for p53 nuclear overexpression was > or =20% of
      tumor cells displaying nuclear staining. The median values for MIB1 (> or =18% of
      tumor nuclear cell staining) and microvascular counts (> or =40 microvessels/area
      screened) were used as cutoff points for these two variables. The assessment of
      DNA content was conducted by classifying cases as diploid, tetraploid, or
      aneuploid. Statistical analyses were performed using the Fisher's Exact Test (2
      tailed). Results revealed that none of the markers studied had a statistically
      significant correlation with the end point of the study, i.e., the presence of
      lymph node metastatic disease, in the cohort of patients studied, although an
      obvious trend for p53 was noted. It is concluded that alterations of p53, Ki-67
      proliferative index, microvascular counts, and ploidy are not strongly associated
      with lymph node status in patients affected with high-stage, high-grade bladder
      cancer.

PMID- 9607587
TI  - A similar pattern of chromosomal alterations in prostate cancers from African
      Americans and Caucasian Americans.
AB  - A combination of genetic and epigenetic factors may explain the disproportionate
      incidence and mortality of prostate cancer among African-American males (AAMs) as
      compared with Caucasian American males (CAMs). We wished to determine whether
      primary prostate cancers from AAMs and CAMs harbor different patterns or
      frequencies of chromosomal alterations. Comparative genomic hybridization (CGH)
      was performed on clinically localized, untreated primary prostate cancers from 16
      AAMs and 16 CAMs. Detailed statistical analysis was used to delineate gains and
      deletions with high sensitivity and specificity and to compare the frequency and
      pattern of alterations between the two groups of tumors. The two groups of
      patients had indistinguishable preoperative serum prostate-specific antigen
      levels, and the two groups of tumors had similar pathological stages and grades.
      Chromosomal gains and deletions occurred in regions known to be frequently
      altered in prostate cancer. Specifically, the most frequent alterations were
      deletions of regions on chromosomes 13q, 5q, 16q, and 8p and gains of regions on
      8q and 5q. When tumors from AAMs and CAMs were compared, the frequencies of
      alteration (deletion, gain, or no alteration) were similar across 98.9% of the
      length of the genome. The patterns of alterations of the most frequently altered
      chromosomes were also similar between tumors from AAMs and CAMs. We concluded
      that primary prostate cancers from AAMs and CAMs harbor a similar pattern and
      frequency of chromosomal alterations. These data support the notion that sporadic
      prostate cancers from AAMs and CAMs develop by similar chromosomal mechanisms.
      Biological differences, if present, do not occur on the chromosomal level.

PMID- 9607588
TI  - Preoperative serum vascular endothelial growth factor can predict stage in
      colorectal cancer.
AB  - Neovascularization has been shown to be essential for the growth of solid tumors.
      Vascular endothelial growth factor (VEGF) is one of the most important mediators
      of angiogenesis. This study was conducted to determine the significance of this
      cytokine as a tumor marker for staging colorectal cancer. Preoperative serum VEGF
      was measured in 108 colorectal cancer patients and in 136 normal healthy
      controls. The results of this study showed a significant difference between the
      four T classes, Union International Contre Cancer (UICC) stages, and Dukes'
      stages. In comparison to serum levels in controls (median, 173.8 pg/ml), VEGF
      levels were significantly elevated in T2 (P = 0.003), T3, and T4 (P < 0.0005);
      UICC I (P = 0.001), UICC II, UICC III, and UICC IV (P < 0.0005); and Dukes' A (P
      = 0.001), Dukes' B, and Dukes' C (P < 0.0005). Serum VEGF showed a significant
      elevation over control in node-negative (P < 0.0005) and in node-positive
      colorectal cancer (P < 0.0005) patients. Node-positive cancer had a significant
      elevation of serum VEGF compared to node-negative cancer (P = 0.008). This study
      reveals that preoperative serum VEGF can detect all but very early colorectal
      cancer i.e., T1 (P = 0.06).

PMID- 9607589
TI  - Differential quantitative effects of interleukin (IL)-2 and IL-15 on cytotoxic
      activity and proliferation by lymphocytes from patients receiving in vivo IL-2
      therapy.
AB  - Lymphocytes from patients receiving in vivo interleukin (IL)-2 therapy possess
      enhanced in vitro proliferative and cytotoxic responses to IL-2. The cells from
      these patients that respond to exogenous IL-2 are CD56+ natural killer cells
      expressing intermediate-affinity IL-2 receptor betagamma(c) complexes. Because IL
      15 activates cells via these same betagamma(c) receptors, we hypothesized that IL
      15 would also activate lymphocytes from patients treated with in vivo IL-2
      therapy and therefore that IL-15 might potentially be useful as an
      immunotherapeutic agent alone or in combination with IL-2. We report here that
      peripheral blood mononuclear cells (PBMCs) from patients receiving in vivo IL-2
      therapy do proliferate in response to IL-15. However, a greater dose of IL-15 is
      needed to reach the same level of proliferation stimulated by IL-2. The EC50 for
      IL-2 is 0.21 +/- 0.04 nM (mean +/- SE; n = 18), whereas the EC50 for IL-15
      stimulated proliferation is 1.16 +/- 0.16 nM (n = 18). In contrast to the
      proliferative response, equivalent doses of IL-2 and IL-15 stimulate patient
      PBMCs to mediate similar levels of cytotoxicity against Daudi, K562, and LA-N-5
      tumor targets. Notably, low concentrations of IL-15 that do not stimulate a
      substantial proliferative response (e.g., 1.0 ng/ml) do boost PBMCs to mediate
      cytotoxicity against these tumor targets. These distinct dose-response curves for
      proliferation compared to cytotoxicity suggest that IL-15 should be evaluated for
      its potential as an immunotherapeutic agent to treat cancer, particularly in
      regimens providing doses that might minimize the proliferative response
      (associated with cytokine release and toxic side effects) while maintaining the
      cytolytic antitumor response.

PMID- 9607590
TI  - Effect of immunosuppressive agents on the immunogenicity and efficacy of an
      immunotoxin in mice.
AB  - Immunotoxins (ITs) are potent cytotoxic agents used in the treatment of cancer,
      autoimmune disease, and graft-versus-host disease. Results from clinical trials
      demonstrate that many IT-treated patients, especially those with an intact immune
      system, develop anti-IT antibodies that may prohibit repeated IT dosing. We,
      therefore, evaluated a panel of novel immunosuppressive (IS) agents for their
      ability to inhibit the antitoxin immune response in mice receiving multiple
      courses of a ricin A chain (RTA)-containing IT and also assessed whether this
      suppression would result in an increase in IT-mediated antitumor activity. The
      results indicate that a 3-day pretreatment, plus one additional boost 2 weeks
      later, of a combination of hCTLA4Ig + anti-CD40L, virtually eliminated the anti
      RTA response in normal mice receiving six weekly injections of an IT. When tested
      in BCL1 tumor-bearing mice, the concomitant use of a combination of hCTLA4Ig +
      anti-CD40L and six doses of the IT resulted in a 1.5-fold increase in tumor cell
      killing, as compared with treatment with IT alone. We conclude that a combination
      of IS + IT therapy should facilitate the administration of multiple courses of
      IT, as well as enhance its antitumor activity.

PMID- 9607591
TI  - Bryostatin 1 down-regulates mdr1 and potentiates vincristine cytotoxicity in
      diffuse large cell lymphoma xenografts.
AB  - The down-regulation of multidrug resistance (mdr1) gene expression as detected by
      competitive reverse transcription-PCR and the antitumor activity of bryostatin 1
      (Bryo1) are investigated in a newly established cell line from a patient with
      relapsed diffuse large cell lymphoma (DLCL). The cell line (WSU-DLCL2) grows in
      liquid culture and forms s.c. tumors in mice with severe combined immune
      deficiency. WSU-DLCL2 is a mature B-cell line (IgG lambda) that is negative for
      EBV nuclear antigen, expresses the multidrug resistance phenotype, and has
      t(14;18)(q32;q21) plus other chromosomal aberrations. Exposure of the WSU-DLCL2
      cells to Bryo1 in culture reversed the multidrug resistance phenotype within 24
      h. A functional assay revealed a 4-fold increase in [3H]vincristine accumulation
      in Bryo1-treated cells compared with control. Vincristine (VCR), doxorubicin,
      Bryo1, and 1-beta-D-arabinofuranosylcytosine showed no clinically significant
      activity when given alone to WSU-DLCL2-bearing severe combined immune deficiency
      mice. However, when given 24 h before each cytotoxic agent, Bryo1 substantially
      increased the antitumor activity of VCR but not 1-beta-D
      arabinofuranosylcytosine. There was a statistically significant (P < 0.001)
      decrease in the expression of P-glycoprotein in WSU-DLCL2 tumors taken from Bryo1
      treated animals compared with untreated controls. In vivo, a competitive reverse
      transcription-PCR assay revealed decreased mdr1 RNA expression 24 h after Bryo1
      treatment. These findings taken together indicate that Bryo1-induced down
      regulation of mdr1 might be one mechanism by which Bryo1 potentiates VCR
      activity. The sequential use of both agents resulted in clinically significant
      antitumor activity in this lymphoma model.

PMID- 9607592
TI  - Restoration of wild-type p53 activity in p53-null HL-60 cells confers multidrug
      sensitivity.
AB  - HL-60 cells that stably express transfected wild-type (wt) p53 were used to
      determine whether restoration of wt p53 increased the chemosensitivity of cells
      that normally lack p53 activity. The wt p53 HL-60 transfectants (SN3 cells) were
      more sensitive than the parental (S) cells to a number of common anticancer drugs
      representing various mechanisms of action, whereas HL-60 cells transfected with
      p53 genes mutated at codons 248 and 143 were not sensitized. The sensitization
      ratio due to the transfected wt p53 varied from about 2-fold for cisplatin to
      over 50-fold for thymidine. Cells treated with the thymidylate synthase inhibitor
      5-fluoro-2'-deoxyuridine (FdUrd) were used to study changes in various p53
      associated gene expressions. A higher percentage of apoptotic cells among the SN3
      cells was observed than among the S cells at each concentration of FdUrd. The S
      cells had undetectable levels of bax and high levels of bcl-2, whereas the SN3
      cells had undetectable levels of bcl-2 levels and appreciable basal levels of
      bax. After FdUrd treatment of SN3 cells, both p53 and bax levels increased, but
      the induction of bax was faster than that of p53 and paralleled the appearance of
      apoptotic DNA laddering. FdUrd treatment induced p21 expression and increased the
      G1 fraction of the SN3 cells but did not induce p21 or change the phase
      distribution in the S cells. FdUrd treatment also induced the expression and
      phosphorylation of cyclin D1 in the SN3 cells but not in the S cells. These
      results show that transfected wt p53 confers multidrug sensitivity to HL-60 cells
      by re-adjustment of the expressions of apoptosis genes and displays other
      properties characteristic of endogenously originated wt p53.

PMID- 9607594
TI  - Antiangiogenic chemotherapeutic agents: characterization in comparison to their
      tumor growth inhibition in human renal cell carcinoma models.
AB  - The mechanism of action of anticancer chemotherapeutic agents is mainly thought
      to be due to a direct inhibition of tumor cell proliferation. The enhanced
      endothelial cell proliferation rate in tumor specimens raised the question of
      whether therapeutic effects of chemotherapeutic agents might be at least
      partially attributed to inhibition of tumor angiogenesis. In the present study,
      we investigated the potential effects of chemotherapeutic agents on human renal
      carcinoma angiogenesis with the alginate implantation model in mice. For the
      first time, we also compared results from the angiogenesis model with the
      inhibitory effects on growth of s.c. xenografts in nude mice. Vincristine and
      bleomycin exerted strong inhibition of tumor angiogenesis in both carcinoma lines
      close to the level of the standard antiangiogenic agent O-chloroacetyl-carbamyl
      fumagillol (AGM-1470; T/C 22%). Adriamycin reduced angiogenesis of Caki-2 cells
      (T/C 33%) but had no effect on Caki-1 angiogenesis (T/C 137%). Etoposide and 5
      fluorouracil reduced Caki-1 tumor angiogenesis but had no effect on Caki-2.
      Despite antiangiogenic effects in both carcinoma lines, vincristine, bleomycin,
      and AGM-1470 significantly reduced only the growth of fast-growing Caki-1 s.c.
      xenografts but not the slow-growing Caki-2. Antivascular effects by bleomycin and
      AGM-1470 were also shown by a decrease of microvessel density in nude mouse
      xenografts. Our findings suggest that chemotherapeutic agents may exert
      inhibition of tumor angiogenesis, which could be exploitable by combination
      therapy of fast-growing tumors. The resistance of the slow-growing Caki-2
      carcinoma against acute angiogenesis inhibition indicates a need for well
      tolerated angiogenesis inhibitors. Our results also suggest the use of fast
      growing s.c. xenografts for demonstrating growth inhibition by antiangiogenic
      compounds. Further characterization of antiangiogenic compounds considered for
      clinical application should, however, have its focus on slow-growing tumors,
      which are not accessible for most therapeutic strategies.

PMID- 9607593
TI  - Schedule-dependent synergism between raltitrexed and irinotecan in human colon
      cancer cells in vitro.
AB  - The quinazoline folate analogue raltitrexed (ZD1694; Tomudex) and the
      camptothecin derivative irinotecan are two new agents showing clinical activity
      against colorectal cancer. To identify the optimal conditions to achieve
      synergistic cytotoxicity before the clinical development of their combination, we
      explored the interactions between ZD1694 and the active metabolite of irinotecan,
      7-ethyl-10-hydroxycamptothecin (SN-38), in vitro. Cytotoxicity was evaluated with
      a clonogenic assay using the human colon cancer cell line HCT-8. Different
      schedules of administration and different dose ratios of the two agents were
      compared and evaluated for synergism, additivity, or antagonism with a
      quantitative method based on the median-effect principle of Chou and Talalay (T.
      C. Chou and P. Talalay, Adv. Enzyme Regul., 22: 27-55, 1984). Sequential short
      term (1 and 4-h) exposures to SN-38 followed by ZD1694 resulted in synergistic
      cytotoxicity at broad dose-effect ranges. At a high level of cell kill, the
      synergism was greater when either equiactive doses of the two agents or higher
      relative doses of ZD1694 were used. A 24-h interval between exposure to SN-38 and
      ZD1694 significantly enhanced the magnitude of the synergy (P = 0.001). The
      opposite sequence or simultaneous exposures produced significantly less
      potentiation or nearly additive interactions (P = 0.0006 and P < 0.0001). The
      synergism was completely lost under conditions of more prolonged drug exposure
      (24-h continuous exposure). In conclusion, in this in vitro model of human colon
      cancer, ZD1694 and SN-38 produced synergistic cytotoxicity. Our findings support
      the clinical use of this combination and provide a rationale for a clinical trial
      using sequential short-term exposures to equiactive doses of SN-38 and ZD1694
      administered sequentially with a 24-h interval.

PMID- 9607595
TI  - Successful treatment of human chronic lymphocytic leukemia xenografts with
      combination biological agents auristatin PE and bryostatin 1.
AB  - We tested the activity of dolastatin 10 (a natural product derived from the shell
      less marine mollusk, Dolabella auricularia, a sea hare) and its structural
      modification, auristatin PE, alone and in combination with bryostatin 1 (a
      protein kinase C activator derived from the marine bryozoan Bugula neritina) on a
      human B-cell chronic lymphocytic leukemia cell line (WSU-CLL) and in a severe
      combined immune deficient (SCID) mouse xenograft model bearing this cell line.
      WSU-CLL cells were cultured in RPMI 1640 at a concentration of 2 x 10(5)/ml using
      a 24-well plate. Agents were added to triplicate wells, and cell count,
      viability, mitosis, and apoptosis were assessed after 24 h of incubation at 37
      degrees C. Results showed that dolastatin 10 had no apparent inhibition of cell
      growth at concentrations less than 500 pg/ml. Auristatin PE, on the other hand,
      showed significant growth inhibition at concentrations as low as 50 pg/ml.
      Auristatin PE-treated cultures, at this concentration, exhibited 27 and 4.5%
      mitosis and apoptosis, respectively. Dolastatin 10, at the same concentration,
      did not exert any effect and was comparable with that of control cultures. In the
      WSU-CLL-SCID mouse xenograft model, the efficacy of these agents alone and in
      combination with bryostatin 1 was evaluated. Tumor growth inhibition (T/C), tumor
      growth delay (T-C), and log10 kill for dolastatin 10, auristatin PE, and
      bryostatin 1 were 14%, 25 days, and 1.98; 2%, 25 days, and 1.98; 19%, 13 days,
      and 1.03, respectively. Auristatin-PE produced cure in three of five mice,
      whereas dolastatin 10 showed activity but no cures. When given in combination,
      auristatin PE + bryostatin 1-treated animals were all free of tumors (five of
      five) for 150 days and were considered cured. Dolastatin 10 + bryostatin 1
      treated animals produced cure in only two of five mice. We conclude that: (a)
      auristatin-PE is more effective in this model than dolastatin 10; (b) auristatin
      PE can be administered at a concentration 10 times greater than dolastatin 10;
      (c) there is a synergetic effect between these agents and bryostatin 1, which is
      more apparent in the bryostatin 1 + auristatin PE combination. The use of these
      agents should be explored clinically in the treatment of CLL.

PMID- 9607596
TI  - Higher potency of N-(4-hydroxyphenyl)retinamide than all-trans-retinoic acid in
      induction of apoptosis in non-small cell lung cancer cell lines.
AB  - Most human non-small cell lung cancer (NSCLC) cell lines are refractory to all
      trans-retinoic acid (ATRA). Recently, N-(4-hydroxyphenyl)retinamide (4HPR) was
      found to induce apoptosis in various tumor cells. In this study, we compared and
      contrasted the effects of 4HPR and ATRA on the growth and apoptosis of 10 NSCLC
      cell lines and normal human bronchial epithelial (NHBE) cells. All of the cancer
      cell lines and the NHBE cells were sensitive to 10 microM 4HPR, and their numbers
      decreased to <20% of the controls after a 5-day treatment, whereas ATRA decreased
      cell numbers to about 50% of the controls in three cell lines and was less
      effective in the rest of the tumor cell lines. ATRA inhibited the growth of the
      NHBE cells by 70-80%. 4HPR induced apoptosis in most of the cells, including the
      ATRA-resistant ones, as evidenced by a DNA fragmentation assay. No correlation
      was found between growth inhibition by 4HPR and the expression of retinoic acid
      receptor beta (determined by Northern blotting and PCR), p53, or Bcl-2 proteins
      (analyzed by Western blotting). These results demonstrate that 4HPR is more
      potent than ATRA in inducing apoptosis in NSCLC cells and suggest that further
      clinical trials for prevention and therapy of NSCLC using 4HPR are warranted.

PMID- 9607597
TI  - Accelerated telomere shortening in fibroblasts after extended periods of
      confluency.
AB  - Telomere length in MRC-5 fibroblasts remains constant if the cells are
      proliferation-inhibited for up to 3 months by confluency. However, the apparent
      frequency of single-stranded sites in telomeres, measured as sensitivity to
      degradation by S1 nuclease, increases about fourfold during this extended
      inhibition of proliferation. After release of the cells, the frequency of
      telomeric single-stranded sites decreases to control values, and the telomere
      shortening rate increases about threefold as compared to controls proliferating
      without inhibition. This acceleration is transitory, the telomere shortening rate
      decreases to control values after about two population doublings after release.
      Finally, temporarily arrested fibroblast populations senesce at a lower
      cumulative population doubling level, but at about the same telomere length, as
      continuously proliferating controls. The data suggest that metabolic time
      dependent single-strand degradation is a major cause of telomere shortening. They
      support the idea that telomere shortening plays an important role in triggering
      cellular senescence.

PMID- 9607598
TI  - Pantothenol protects rats against some deleterious effects of gamma radiation.
AB  - Rats were exposed to gamma radiation from a 60Co source, receiving 0.25 Gy at
      weekly intervals. During 2 d before each irradiation, the animals received daily
      intragastric doses of 26 mg pantothenol or 15 mg beta-carotene per kg body
      weight. One hour after the third irradiation session, the animals were killed and
      their livers were analyzed. In animals not supplied with pantothenol, the
      irradiation resulted in a significant decrease of total liver lipids and a 50%
      decrease in phospholipids. Liver cholesterol was decreased by about 20%.
      Irradiation produced lipid peroxidation as expressed by doubling of the amounts
      of conjugated dienes and ketone dienes and of thiobarbituric acid reactive
      compounds. The amount of CoA in liver was decreased by 24% and that of reduced
      glutathione by 40%. The NAD+/NADH ratio was increased by 60% and the activity of
      NADP-dependent malate dehydrogenase (decarboxylating) was decreased by 26%. The
      amount of pantothenic acid and its derivatives (expressed as pantolactone
      generating compounds) in blood decreased by about 80%. In rats to which
      pantothenol was administered, the content of pantothenic acid in blood was
      tripled compared to nonirradiated (control) rats, and all the biochemical
      parameters measured in liver were the same as in nonirradiated animals.

PMID- 9607599
TI  - Immunohistochemical localization of xanthine oxidase in human retina.
AB  - Xanthine oxidase has been established as an important source of oxygen free
      radicals in ischemia-reperfusion injury. It has been localized in many different
      tissues such as heart and intestine, but it has not yet been localized in the
      eye. Xanthine oxidase was detected using immunohistochemistry on
      paraformaldehyde/glutaraldehyde fixed cryosections. Antibodies used included
      rabbit antibovine xanthine oxidase antibody and rabbit antihuman xanthine oxidase
      antibody. Xanthine oxidase was detected in the capillary endothelium cells of
      blood vessels in the retina of bovine and post mortem human eyes. Whole mount
      preparation of human retinas showed xanthine oxidase present throughout the small
      capillary network. Furthermore, whole mounts showed that xanthine oxidase was
      present in cones. This was confirmed by using mouse anticalbindin antibody for co
      labelling. It is possible that xanthine oxidase can be a source of oxidative
      damage in the retina following ischemia-reperfusion injury.

PMID- 9607600
TI  - Absence of hemoprotein-associated free radical events following oxidant challenge
      of crosslinked hemoglobin-superoxide dismutase catalase.
AB  - Crosslinking hemoglobin with superoxide dismutase and catalase (PolyHb-SOD-CAT)
      helps to limit free radical reactivity of modified hemoglobin red blood cell
      substitutes. In the present study, in vitro oxidant challenge experiments were
      performed with exogenous hydrogen peroxide (H2O2) and xanthine oxidase-derived
      superoxide (O2.-). PolyHb-SOD-CAT was compared to PolyHb for the presence of
      secondary hemoprotein-free radical events. PolyHb-SOD-CAT prevents
      ferrylhemoglobin formation, measured as Na2S-induced absorbance at 620 nm.
      Similarly, PolyHb-SOD-CAT inhibited ferrozine-detectable iron release at high
      oxidant-heme ratios. The formation of oxygen radicals, monitored by salicylate
      hydroxylation, was prevented at high oxidant-heme ratios with PolyHb-SOD-CAT. The
      peroxidation of liposomal membranes was also inhibited in PolyHb-SOD-CAT mixtures
      subject to oxidant challenge. These results show that PolyHb-SOD-CAT prevents
      secondary hemoprotein-associated free radical events. This new type of modified
      hemoglobin oxygen carrier with antioxidant activity may reduce the potential
      toxicity of hemoglobin-based substitutes in certain applications, especially
      during reperfusion of ischemic tissues.

PMID- 9607601
TI  - Antiproliferative effect of the piperidine nitroxide TEMPOL on neoplastic and
      nonneoplastic mammalian cell lines.
AB  - The stable nitroxide 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPOL) is
      widely used as a probe in biophysical studies and as an antioxidant in several
      experimental models. The potential cytotoxic effects of TEMPOL were tested on a
      panel of human and rodent cell lines, and the nitroxide proved to be
      significantly more effective in inhibiting the growth of neoplastic than
      nonneoplastic cell lines after a 96-h exposure. More detailed studies on MCF-7/WT
      cells indicate that at least 24 h are necessary for TEMPOL to induce irreversible
      cell damage, which seems to be related to the reactivity of the nitroxyl group.
      This observation, together with the antagonistic effect of N-acetylcysteine,
      suggests an involvement of free radical-mediated processes. Cell cycle studies
      indicate a biphasic effect of TEMPOL, with a short-term accumulation of the cells
      in the G1 phase and a later increase in G2/M phase; the pattern of DNA
      fragmentation observed in TEMPOL-treated cells points to an apoptotic mode of
      cell death. In conclusion, our data suggest that, while the possible cytotoxic
      effects of TEMPOL should not be overlooked when using this compound as a
      biophysical probe or antioxidant, these same properties could be exploited as a
      novel approach to cancer chemotherapy, especially in tumor cells exhibiting
      unfavorable characteristics, such as a multidrug-resistant phenotype or loss of
      hormone receptors.

PMID- 9607602
TI  - Severe energy impairment consequent to inactivation of mitochondrial ATP synthase
      as an early event in cell death: a mechanism for the selective sensitivity to
      H2O2 of differentiating erythroleukemia cells.
AB  - Irreversible damage to Friend's erythroleukemia cells was caused by induction of
      endogenous heme biosynthesis with the differentiating agent N,N'-hexamethylene
      bisacetamide followed by a 30-min exposure to 0.25 mM H2O2. Early irreversible
      ATP depletion was observed concomitant with oxidative inactivation of the
      mitochondrial ATP synthase. Cell proliferative capacity was also impaired within
      2 h of the treatment, and progressive delayed cell lethality, starting 2 h after
      the insults, was also found. Based on the prevention provided by specific
      antioxidants and on the absence of malodialdehyde production, all the effects
      were ascribed to the oxidant action of .OH radicals, or closely related species,
      generated through iron-catalyzed reactions of H2O2, which apparently caused site
      directed oxidative modifications of iron-binding proteins, in particular
      mitochondrial ATP synthase, rather than peroxidation of membrane lipids. Similar
      effects were mimicked even in the parental cell line when oligomycin was used to
      inhibit selectively mitochondrial ATP synthase activity, thereby lowering the
      enzyme activity to a level similar to that found in H2O2-damaged differentiating
      cells. Hence, induction of erythroid differentiation makes the mitochondrial ATP
      synthase a major target of H2O2 by enhancing the availability of redox-active
      iron in the local environment of the enzyme. Subsequent oxidative inactivation of
      the mitochondrial ATP synthase, resulting in severe energy impairment, leads to
      loss of cell growth capacity. Erythroleukemia cells may serve as a model system
      for the combination of two selective properties: (1) the capacity for carrying
      out efficient heme synthesis and/or for undergoing iron overload-like state; and
      (2) subsequent enhanced sensitivity to reactive oxygen species generators. Early
      severe mitochondrial dysfunction and energy impairment may be a major part of the
      mechanism of the sensitivity.

PMID- 9607603
TI  - Physico-chemical properties and antioxidant activities of methoxy phenols.
AB  - A few structurally related phenols, dehydrozingerone (DZ), bromopentenone (BP),
      eugenol (EG) and isoeugenol (IEG), derived from plant products show antioxidant
      properties by inhibiting lipid peroxidation in membrane models. The phenoxyl
      radicals produced by the scavenging of free radicals during the inhibition of
      lipid peroxidation, were also generated by specific one-electron oxidants using
      pulse radiolysis. The radical lifetimes (second order rate constants for radical
      radical reactions), reactivities with hydroxyl and model peroxyl radicals and the
      one-electron reduction potentials with respect to the standard couples were
      quantified. These results along with their lipophilicity data were correlated
      with their antioxidant activity (IC50 values).

PMID- 9607604
TI  - Effect of oxidative stress on brain damage detected by MRI and in vivo 31P-NMR.
AB  - The brain is susceptible to oxidative stress. This is due to the high content of
      polyunsaturated fatty acids, high rate of oxygen consumption, regional high
      concentrations of iron, and relatively low antioxidant capacity. These factors
      may predispose the premature infant to brain damage. Brain damage may be due to:
      1. Brief anoxia followed by hyperoxia (mimics parturition oxidative stress); or
      2. Prolonged exposure to hyperoxia (mimics oxidative stress from postpartum
      maintenance in a hyperoxic environment). We have developed two animal models to
      examine these forms of oxidative stress on the brains of rats. In Model I rats
      were exposed to brief anoxic anoxia (100% N2) followed by hyperoxia (100% O2).
      Using T2-weighted Magnetic Resonance Imaging (MRI) brain intensity decreased
      following the treatment suggesting water loss or free radical production. In vivo
      1H-NMR showed brain water content appeared to increase, however variability
      rendered this result insignificant. Electron spin resonance (ESR) spin trapping,
      using a-phenyl-N-tert-butylnitrone (PBN) produced a free radical signal from the
      anoxic-anoxia hyperoxia treated animals which suggests the decrease in MRI T2
      weighted image signal intensity was due to free radicals. In Model II, we
      examined the effects of prolonged normobaric hyperoxia (85% O2) on blood-brain
      barrier (BBB) integrity and brain phosphorous metabolism. BBB permeability
      increased following 1 week of hyperoxia. In addition, measurement of high energy
      phosphates, using in vivo 31P-NMR, showed the PCr/ATP ratio significantly
      decreased, the ATP/Pi ratio increased and the (ATP+PCr)/Pi ratio increased.
      Because the BBB is sensitive to oxidative stress its loss of integrity may be due
      to free radicals. The level of oxidative stress may result in brain elevation of
      ATP as an adaptation mechanism. In conclusion, anoxic-anoxia and prolonged
      hyperoxia exposure produce MRI visible changes in the brain. These two mechanisms
      may be important in the etiology of brain damage observed in many premature
      infants.

PMID- 9607605
TI  - Ozone-induced airway hyperresponsiveness in patients with asthma: role of
      neutrophil-derived serine proteinases.
AB  - Proteinase inhibitors may be of potential therapeutic value in the treatment of
      respiratory diseases such as chronic obstructive pulmonary disease (COPD) or
      asthma. Our aim was to study the role of neutrophils, and neutrophil-derived
      serine proteinases in an acute model in patients with asthma. Exposure to ozone
      induces an acute neutrophilic inflammatory reaction accompanied by an increase in
      airway hyperresponsiveness. It is thought that these two effects of ozone are
      linked, and that neutrophil-derived serine proteinases (i.e. elastase) may play a
      role in the ozone-induced airway hyperresponsiveness. Therefore, we examined the
      effect of recombinant antileukoprotease (rALP), one of the major serine
      proteinase inhibitors in the lung, on ozone-induced changes in airway
      hyperresponsiveness in this model. We observed that 16 h after exposure to ozone,
      airway hyperresponsiveness to methacholine was increased both following placebo
      and rALP treatment. There was no significant difference between placebo and rALP
      treatment (change in area under the dose-response curve to methacholine: 117.3+/
      59.0 vs 193.6+/-59.6 % fall x DD; p=.12). Moreover, the immediate decrease in
      FEV1 after ozone exposure was not significantly different between the two groups
      (placebo: -29.6+/-6.7%; rALP: -20.9+/-3.8%; p=.11). In addition, no significant
      differences were observed in plasma levels of fibrinogen degradation products
      generated by neutrophil serine proteinases before and after exposure to ozone. We
      conclude that neutrophil-derived serine proteinases are not important mediators
      for ozone-induced hyperresponsiveness.

PMID- 9607606
TI  - A chromatographic assay for heme oxygenase activity in cultured human cells:
      application to artificial heme oxygenase overexpression.
AB  - Heme oxygenase (HO) activity oxidizes heme, releasing carbon monoxide; heme iron;
      and biliverdin, which is converted to bilirubin by biliverdin reductase.
      Inducible HO-I expression is a marker of oxidative stress in mammalian cells,
      while noninducible HO-II contributes to basal HO activity. HO-I and HO-II
      activities are implicated in cellular antioxidant defense mechanisms. We describe
      a microassay for HO activity in cultured human cells, using high-performance
      liquid chromatography of biliverdin and bilirubin. The assay is sufficiently
      sensitive to quantify basal and inducible HO activity in various human cell
      types. We have established human cell lines overexpressing heme oxygenase-II
      activity in microsomes using a metallothionein promoter-regulated expression
      system. Stable transformants treated with ZnCl2 express up to ninefold induction
      of HO activity. We have constructed human cell lines overexpressing HO-II protein
      and activity (5-15-fold) in the absence of tetracycline, using the HtTA-1 cell
      line transfected with tetracycline-regulated expression vectors (Gossen et al.,
      Proc. Natl. Acad. Sci. USA 89, 1992). Functional HO-II overexpressing clones will
      be useful in investigating anti- or pro-oxidant effects of HO activity during
      cellular oxidative stress.

PMID- 9607607
TI  - DNA strand break induction and enhanced cytotoxicity of propyl gallate in the
      presence of copper(II).
AB  - The antioxidant propyl gallate (PG) induced single strand breaks in PM2 DNA at
      concentrations higher than 0.25 microM when it was combined with copper
      concentrations at 5 microM and above. In combination with 100 microM CuCl2,
      extensive double strand breakage was also observed. Neither PG alone nor CuCl2
      showed any strand breaking properties. DNA strand breakage was inhibited by
      addition of catalase or the Cu(I) chelator neocuproine, indicating the
      involvement of H2O2 and a Cu(II)/Cu(I) redox cycle in the DNA damage. DNA damage
      of PG/Cu(II) was also observed in human fibroblasts. Using the alkaline elution
      technique concentrations of 0.15-0.5 mM PG induced DNA strand breaks in
      combination with 2.5 mM CuCl2, while the single substances did not show any
      effect. At these concentrations cell viability measured by the MTT assay was not
      reduced by more than 10%; however, cell growth was inhibited by PG in combination
      with Cu(II). This growth inhibition was apparently due to the DNA damage incurred
      by PG/Cu(II). The synergistic interaction between PG and Cu(II) is probably
      caused by a redox reaction between both compounds, whereby reactive species such
      as ROS are formed, which are responsible for the observed genotoxic and cytotoxic
      effects. Our results demonstrate that the antioxidative and cytoprotective
      properties of propyl gallate may change to prooxidative, cytotoxic and genotoxic
      properties in the presence of Cu(II).

PMID- 9607608
TI  - ICAM-1 and VCAM-1 expression induced by TNF-alpha are inhibited by a glutathione
      peroxidase mimic.
AB  - Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1
      (VCAM-1) are respectively involved in the endothelial recruitment of neutrophils,
      and in that of lymphocytes or tumor cells, in response to specific signals. We
      have used the glutathione peroxidase (GPx) mimic BXT-51072 to assess the
      possibility that endogenous hydroperoxides play a role in the tumor necrosis
      factor-alpha (TNFalpha)-induced expression of ICAM-1 and VCAM-1 by monolayers of
      human endothelial cells. The GPx mimic BXT-51072 strongly inhibits the TNFalpha
      induced and cycloheximide-sensitive expression of ICAM-1 and VCAM-1. It also
      inhibits the TNFalpha-induced reorganization of the actin network and the
      associated formation of stress fibers. Actin reorganization induced by
      cytochalasin D treatment did not inhibit ICAM-1 expression. Our results are
      compatible with specific and synergistic effects of endogenous hydroperoxides on
      the biosynthesis and processing of cell adhesion molecules and cytoskeleton
      components.

PMID- 9607609
TI  - Striatal dopamine dynamics are altered following an intranigral infusion of iron
      in adult rats.
AB  - In vivo electrochemical detection was employed to examine iron-induced oxidative
      injury on dopamine dynamics in the nigrostriatal system of urethane-anesthetized
      rats. Seven days after an intranigral infusion of iron, oxidative stress was
      confirmed by an elevated lipid peroxidation in lesioned substantia nigra (SN).
      Local application of potassium (K+) evoked dopamine releases from the dopamine
      containing nerve terminals in the striatum. Both amplitude and rate of clearance
      (Tc) of evoked dopamine releases were lower in striatum with lesioned SN;
      however, the time course parameters of dopamine release in the lesioned group
      were not different from those of the intact group, indicating a reduction in
      dopamine clearance. Indeed, iron-induced oxidative stress attenuated the effect
      of nomifensine, a high-affinity dopamine uptake blocker, on dopamine clearance.
      In striatum with intact SN, the amplitude and time course parameters of signals
      by exogenous dopamine were increased and Tc was decreased by nomifensine. In
      contrast, nomifensine did not significantly alter the dopamine signals of the
      lesioned group. Taken together, in addition to the increased lipid peroxidation
      in SN, our in vivo electrochemical data demonstrates that iron-induced oxidative
      injury attenuates K+-evoked dopamine release and dopamine uptake in the
      ipsilateral striatum. The diminished nomifensine effect implies a lack of high
      affinity dopamine uptake sites.

PMID- 9607610
TI  - Development of glutathione synthesis and gamma-glutamyltranspeptidase activities
      in tissues from newborn infants.
AB  - Following the observation that the level of glutathione in leukocytes from human
      newborn infants was lower in preterm and in male infants, a study was designed to
      document the level of activities of glutathione synthesis and gamma
      glutamyltranspeptidase during the development of preterm and term newborn
      infants. Measurements were performed in leukocytes from tracheal aspirates of
      oxygen dependent infants, and in leukocytes from cord blood. Contrary to the
      common belief concerning the development of antioxidant activity, the
      biosynthesis of glutathione was active in leukocytes from preterm infants; and by
      two days of life the activity of gamma-glutamyltranspeptidase reached 3 times the
      level of that seen in cord blood. Our results suggest that the maturity of these
      enzymes was not the limiting step in maintaining cellular glutathione levels.
      This represents new information concerning the maturation of a central
      antioxidant in tissue derived from preterm and term human newborn infants at risk
      of oxidant stress. This implies that sources of cysteine crossing freely the
      cellular membrane could be used by tissues of term and preterm infants to produce
      glutathione.

PMID- 9607611
TI  - Free radical formation during ketamine anesthesia in rats: a cautionary note.
AB  - Ketamine is a useful anesthetic agent with good analgesic properties; however,
      when ketamine was used to anesthetize rats for spin trapping studies of alcohol
      induced free radicals, liver extracts contained a strong electron paramagnetic
      resonance (EPR) signal of a novel radical. The same EPR signal was observed in
      liver extracts when rats which had not received alcohol were anesthetized with
      ketamine. When ketamine was added to liver microsomes and NADPH, a nitroxide
      radical derived from ketamine could be detected in organic extracts. When the
      spin trapping agent POBN was also added, microsomes produced both a ketamine
      nitroxide radical and a spin adduct. Similar results were obtained during
      ketamine oxidation by hydrogen peroxide in a tungstate-catalyzed reaction, or in
      a Fenton reaction system. The data suggest that the secondary amine group of
      ketamine can be oxidized to a stable nitroxide which produces an EPR spectrum in
      the absence of a spin trapping agent. The POBN spin adduct detected may be from a
      carbon-centered radical in the cyclohexanone ring of ketamine. Because several
      types of radicals can be formed from ketamine, this agent may not be appropriate
      as an anesthetic for many types of in vivo spin trapping experiments.

PMID- 9607612
TI  - The correlation of the weakening effect on gastric mucosal integrity by 5-HT with
      neutrophil activation.
AB  - The effects of 5-hydroxytryptamine (5-HT) on ethanol-induced gastric mucosal
      damage and on epithelial and vascular integrity were investigated. Male Sprague
      Dawley rats were administered with 5-HT (5 or 10 mg/kg, IP) 30 min prior to the
      challenge with ethanol (40% v/v, 10 ml/kg, PO). 5-HT dose dependently aggravated
      ethanol-induced injury in the gastric mucosa. Both xanthine oxidase (XO) and
      myeloperoxidase (MPO) activities in the mucosa were significantly increased with
      the high dose of 5-HT, which also potentiated the elevation of these enzyme
      activities by ethanol. However, the mucosal superoxide dismutase activity was
      left unaltered. In neutropenic (antineutrophil serum-treated) animals, the
      ethanol-induced gastric mucosal injury was significantly ameliorated, with or
      without the pretreatment of 5-HT (10 mg/kg). In addition, the effect of 5-HT on
      the activity of MPO, but not of XO, was also attenuated in these animals. In the
      ex vivo gastric chamber study on pentobarbital-anesthetized animals, volume of
      gastric secretion was significantly decreased in the 5-HT-treated groups, with
      further reduction after ethanol incubation. Transmucosal potential difference
      (PD) was significantly reduced in 5-HT-treated rats, which also potentiated the
      ethanol-induced drop in PD. Nevertheless, 5-HT dose dependently increased mucosal
      vascular permeability and further enhanced during ethanol incubation. These
      findings suggest that 5-HT adversely affects the defense mechanisms of the
      gastric mucosa by reducing the secretory function of the mucosal cells and to
      weaken the epithelial and vascular integrity. Neutrophil activation appears to be
      responsible for the detrimental effects of 5-HT partly through the elevation in
      MPO activity. The increase in mucosal XO activity by 5-HT may induce free radical
      production and possibly modulate the ulcerogenic processes.

PMID- 9607613
TI  - Role of cadherin internalization in hydrogen peroxide-mediated endothelial
      permeability.
AB  - Exposure of endothelial monolayers to hydrogen peroxide results in increased
      solute permeability in a time- and dose-dependent fashion. This effect is
      prevented by either staurosporine, an inhibitor of PKC, or by Go6976, an
      inhibitor of "classical" PKC isoforms. Immunohistochemistry of peroxide-treated
      monolayers illustrates a loss of cadherin staining at cell junctions and gap
      formation predominantly at tri-cellular junctions. Both staurosporine and Go6976
      prevented peroxide-induced gap formation. Peroxide also stimulated
      internalization of cadherins as measured by the trypsin protection assay, which
      was not blocked by staurosporine or Go6976. These data suggest that peroxide
      causes: 1) a time- and dose-dependent increase in permeability and dose-dependent
      increase in gap formation, both of which are PKC dependent; and 2) promotes PKC
      independent cadherin internalization. These data indicate that cadherin
      internalization may be part of the mechanism through which oxidants regulate
      solute permeability.

PMID- 9607614
TI  - Alpha-lipoic acid in liver metabolism and disease.
AB  - R-alpha-Lipoic acid is found naturally occurring as a prosthetic group in alpha
      keto acid dehydrogenase complexes of the mitochondria, and as such plays a
      fundamental role in metabolism. Although this has been known for decades, only
      recently has free supplemented alpha-lipoic acid been found to affect cellular
      metabolic processes in vitro, as it has the ability to alter the redox status of
      cells and interact with thiols and other antioxidants. Therefore, it appears that
      this compound has important therapeutic potential in conditions where oxidative
      stress is involved. Early case studies with alpha-lipoic acid were performed with
      little knowledge of the action of alpha-lipoic acid at a cellular level, but with
      the rationale that because the naturally occurring protein bound form of alpha
      lipoic acid has a pivotal role in metabolism, that supplementation may have some
      beneficial effect. Such studies sought to evaluate the effect of supplemented
      alpha-lipoic acid, using low doses, on lipid or carbohydrate metabolism, but
      little or no effect was observed. A common response in these trials was an
      increase in glucose uptake, but increased plasma levels of pyruvate and lactate
      were also observed, suggesting that an inhibitory effect on the pyruvate
      dehydrogenase complex was occurring. During the same period, alpha-lipoic acid
      was also used as a therapeutic agent in a number of conditions relating to liver
      disease, including alcohol-induced damage, mushroom poisoning, metal
      intoxification, and CCl4 poisoning. Alpha-Lipoic acid supplementation was
      successful in the treatment for these conditions in many cases. Experimental
      studies and clinical trials in the last 5 years using high doses of alpha-lipoic
      acid (600 mg in humans) have provided new and consistent evidence for the
      therapeutic role of antioxidant alpha-lipoic acid in the treatment of insulin
      resistance and diabetic polyneuropathy. This new insight should encourage
      clinicians to use alpha-lipoic acid in diseases affecting liver in which
      oxidative stress is involved.

PMID- 9607615
TI  - The molecular pathobiology of cell membrane iron: the sickle red cell as a model.
AB  - The molecular pathobiology of membrane-associated iron is clearly illustrated by
      the sickle red blood cell. The cytosolic aspect of the membranes of these cells
      carries several discrete iron compartments, including denatured hemoglobin and
      free heme, as well as molecular iron associated with membrane aminophospholipid
      and denatured globin. Affinity of the membrane for molecular iron is
      extraordinarily high and predicted to keep cytosolic free iron concentration <
      10(-20) M. Membrane iron is bioactive and able to valence cycle, thus serving as
      a catalyst for generation of highly reactive hydroxyl radical. As a consequence
      of this oxidative biochemistry at the cytosol/membrane interface, multiple
      membrane defects arise that are of pathophysiologic importance. Thus, sickle red
      cells provide a pathobiologic paradigm for the membrane-damaging effect of iron
      mediated targeting of oxidative damage at a sub-cellular level. This is relevant
      to a variety of biologic conditions accompanied by decompartmentalization of
      iron.

PMID- 9607616
TI  - Erythrocyte glutathione balance and membrane stability during preeclampsia.
AB  - This study aimed to determine whether oxidative damage to the erythrocyte occurs
      in preeclampsia, and relates to disease severity. The oxidative status of intact
      erythrocytes from preeclamptic patients and normal pregnant women was determined
      using spin echo 1H-NMR, which measures both the concentration and redox state of
      intracellular glutathione. Previous studies of preeclampsia have only measured
      total glutathione levels. Membrane fragility was determined from the degree of
      lysis caused by incubation in hypotonic saline. Erythrocytes from moderate-severe
      preeclamptic patients underwent more lysis than erythrocytes from control
      pregnant women (p < .05) or mild preeclamptic patients. It is suggested that
      increased lysis results from oxidative damage to the erythrocyte membrane,
      causing a decrease in membrane fluidity and reducing its ability to withstand
      osmotic changes. Intracellular glutathione was more oxidized in erythrocytes from
      pregnant women compared to nonpregnant controls (p < .05), and there was a less
      significant trend toward more oxidized glutathione with increasing severity of
      preeclampsia. The moderate-severe group showed a clear division in glutathione
      redox status: some patients had very oxidized glutathione while others had a
      normal redox balance. This novel finding suggests that some patients may be
      unusually susceptible to erythrocyte glutathione oxidation, possibly leading to
      general cellular damage, in particular HELLP Syndrome.

PMID- 9607617
TI  - In vivo analysis of hydrogen peroxide and lipid radicals in the striatum of rats
      under long-term administration of a neuroleptic.
AB  - It has been hypothesized that free radicals play a causative role in tardive
      dyskinesia, which is an inveterate movement disorder caused by chronic
      administration of neuroleptics. To verify this hypothesis, rats were reared while
      being regularly treated with water containing a neuroleptic, haloperidol (HPD),
      for 1 year (HPD group). The changes in the striatal hydrogen peroxide content of
      the rats in the HPD and control groups were measured by using a Pt-disk
      microelectrode while the animals were in a freely moving state following
      intraperitoneal administration of HPD (HPD challenge). We also performed electron
      spin resonance (ESR) detection of lipid radicals in the striatum before the HPD
      challenge. HPD challenge led to significant elevation of the intrastriatal
      hydrogen peroxide in all animals, but the elevation in the HPD group was smaller
      than that in the control group. However, in the HPD group, marked ESR signals of
      intrastriatal lipid radicals were observed. We think that these results support
      the hypothesis on the role of free radicals in tardive dyskinesia.

PMID- 9607618
TI  - p53 protein overexpression and response to induction chemoradiation therapy in
      patients with locally advanced rectal adenocarcinoma.
AB  - BACKGROUND: The association between mutations in the p53 gene and prognosis in
      colorectal cancer remains controversial. This report evaluates the role of p53
      protein to predict the response of neoadjuvant chemoradiation therapy in patients
      with primary locally advanced rectal adenocarcinoma. METHODS: Between January
      1993 and December 1994, 26 patients were seen with locally advanced primary
      rectal adenocarcinoma, located between 0 and 10 cm from the anal verge,
      demonstrated clinically and by CT scan. Each received 45 Gy of preoperative
      radiation therapy (RT) concomitantly with bolus infusion of 5-fluorouracil (5-Fu)
      (450/mg/m2 on days 1 to 5 and 28 to 33 of RT). Surgery was performed between 4
      and 8 weeks later. All the primary tumors were mapped and sliced. The response
      rate was divided according to the percentage of malignant cells in the rectal
      wall and perirectal fat. Lymph nodes were studied with the manual or modified
      clearing technique. p53 mutant status was assessed immunohistochemically from
      sections of the formalin-fixed, paraffin-embedded pretreatment biopsy and the
      resected specimen. RESULTS: There were 14 females and 12 males, with a mean age
      of 54 years. All received the scheduled treatment. An abdominoperineal resection
      (n = 10), low anterior resection (n = 10), and pelvic exenteration (n = 6) were
      performed. The stages of tumors were as follows: no residual tumor (n = 4); T2 (n
      = 6); T3-4 (N = 9); and T3-4, N1,2 (n = 7). Fourteen specimens (54%) had mutated
      p53, and 10 (71%) had >50% of residual tumor, whereas only two (17%) of the
      specimens with normal p53 had >50% of residual tumor (P = .018). Eight of the 10
      low anterior resections were performed in patients whose specimens expressed
      normal p53. CONCLUSION: Our results suggest that the determination of p53 is a
      factor in predicting tumor response in patients who undergo preoperative
      chemoradiation therapy for rectal adenocarcinoma.

PMID- 9607619
TI  - T-cell evaluation in patients with colon cancer: dinitrochlorobenzene skin
      testing versus plasma levels of sIL-2r and sCD8.
AB  - BACKGROUND: Developing reliable methods to test the T-cell system may be
      important in the treatment of colon cancer patients with 5
      fluorouracil/levamisole. In a pilot study we explored whether DNCB
      (dinitrochlorobenzene) skin testing correlated with plasma levels of soluble
      interleukin-2 receptor (sIL-2r) and soluble CD8 (sCD8) and, secondly, whether the
      application of DNCB had any influence on the production of sIL-2r and sCD8.
      METHODS: In 10 patients with advanced colon cancer and in 10 healthy volunteers,
      plasma levels of sIL-2r and sCD8 were measured before and 10 days after the
      application of 2 mg DNCB on the inner side of the forearm. RESULTS: As expected,
      colon cancer patients showed a depressed immune system compared to healthy
      volunteers (DNCB skin test: P = .005, sIL2r [medians 700 vs 295, P = .002], sCD8
      [medians 158 vs 90, P = .03], M-W test). The plasma levels for sIL-2r and sCD8
      were significantly lower in the skin-positive cases (P = .01 and P = .03, M-W
      test). However, a large overlap in plasma levels could be observed between the
      two skin categories. DNCB had no influence on the production of sIL-2r and sCD8;
      median change skin-negative and skin-positive -10 vs +25, P = .14, respectively;
      48 vs 0, P = .32 (M-W test). CONCLUSIONS: DNCB skin testing and plasma levels of
      sIL-2r and sCD8 seem to be equally useful in evaluating the T-cell system and can
      be used simultaneously.

PMID- 9607620
TI  - Wilms tumor presenting with abdominal pain: a special subgroup of patients.
AB  - BACKGROUND: Although significant progress has been made in the management of
      children with Wilms tumor, two major controversies still exist: the extent of
      radiographic evaluation necessary before surgery and the role of preoperative
      chemotherapy. This study sought to determine whether patients with Wilms tumor
      who presented with abdominal pain defined a special subset of patients who might
      require a more extensive preoperative work-up and neoadjuvant chemotherapy.
      METHODS: From 1970 to 1995, 250 children were treated for Wilms tumor at a single
      pediatric institution. A retrospective chart review determined presenting signs
      and symptoms for each patient. RESULTS: Thirty-four (14%) patients (mean age 5.5
      years) sought medical attention with a chief complaint of abdominal pain. The
      stage distribution for these patients tended to be higher and was significantly
      different (P <.001, chi(2)-analysis) from those presenting without pain. Four
      (14%) of 29 patients with tumor available for analysis were found to have
      anaplastic histology. CONCLUSION: These data suggest that patients with Wilms
      tumor who present with abdominal pain represent a special subgroup that tends to
      be older and has an increased incidence of tumor rupture, anaplasia, and higher
      stage. These patients may benefit from a more extensive preoperative evaluation
      and consideration of neoadjuvant chemotherapy.

PMID- 9607621
TI  - Effects of perioperative blood transfusion on prognosis in early-stage cervical
      cancer.
AB  - BACKGROUND: This study was designed to evaluate the prognostic effects of
      transfusion on patients undergoing radical hysterectomy for early cervical
      cancer. METHODS: This retrospective chart review analyzed 412 patients with stage
      IA-IIA disease, of whom 374 were evaluable. RESULTS: Three hundred (80%) patients
      received transfusions and 74 (20%) did not. The clinical characteristics of the
      two groups were similar, with the exception that the transfused group was older.
      Pathologic comparisons found that microscopic parametrial disease and larger
      cervical lesions were more common in the transfused group. Follow-up analysis
      revealed no difference between the two groups in recurrence or survival.
      Multivariate analysis found only grade, depth of invasion, and nodal status as
      independent predictors of recurrence and survival. Kaplan-Meier survival analysis
      showed no difference in overall survival or disease-free interval between the
      transfused and nontransfused groups. CONCLUSIONS: After correction for other
      prognostic factors, blood transfusion had no prognostic significance in patients
      with early cervical cancer undergoing radical hysterectomy.

PMID- 9607622
TI  - Use of touch preps for diagnosis and evaluation of surgical margins in breast
      cancer.
AB  - BACKGROUND: The best cosmetic results with conservative breast surgery are
      obtained at the time of initial excisional biopsy. The usefulness of the touch
      prep (TP) technique was evaluated for accuracy in diagnosis as well as in
      evaluation of margins at the time of original breast biopsy. METHODS: Four
      hundred twenty-eight consecutive patients with breast masses seen from January
      1993 to December 1994 were evaluated prospectively using TP. RESULTS: Three
      hundred forty-five benign and 83 malignant tumors were evaluated. Tumors ranged
      in size from microscopic to 8 cm. Pathologic diagnosis was correct as compared to
      permanent section in 99.3%. The three carcinomas missed on TP were focal and in
      situ. Sensitivity was 96.39%, and specificity was 100%. Positive predictive value
      was 100%, and negative predictive value was 99.3%. For margin evaluation, the
      sensitivity and specificity were both estimated to be 100%. CONCLUSIONS: TP has
      the advantage of being a simple, quick (2 to 3 minutes), safe (no loss of
      diagnostic material), and accurate method for diagnosis and estimation of tumor
      margins at the time of the original surgery.

PMID- 9607623
TI  - Evaluation of axillary lymphadenectomy without axillary drainage for patients
      undergoing breast-conserving therapy.
AB  - BACKGROUND: The routine use of drainage after axillary node dissection in
      patients undergoing breast-conserving therapy (BCT) is being questioned. To
      determine the value of routine drainage, we evaluated the postoperative course of
      patients with primary breast carcinoma who underwent axillary dissection with or
      without axillary drainage. METHODS: A retrospective review of 69 patients
      prompted a prospective randomized trial of 46 patients undergoing BCT at our
      tertiary cancer center. Variables studied were age, treatment (drain or no
      drain), number and tumor status of excised lymph nodes, size of primary tumor,
      duration of drainage or aspiration, number and volume of aspirations, number of
      office visits, incidence of complications and degree of pain, change in arm or
      forearm circumference, and body mass index (BMI). Data from prospective and
      retrospective studies were pooled for analysis. RESULTS: Of 115 patients, 72 were
      treated with a drain (Drain group) and 43 were not (No-drain group). Overall
      there was no difference in the number or tumor status of excised nodes, the size
      of the primary tumor, or the incidence of complications between the two groups.
      Aspiration was required in 50% of the No-drain patients and 8.3% of the Drain
      patients. The incidence of drain placement or replacement postoperatively was
      9.3% for the No-drain patients and 4.2% for the Drain patients. The No-drain
      patients had more office visits (5.1 +/- 0.4 vs. 3.6 +/- 0.1; P = .0002) and a
      longer interval between operation and last aspiration or drain removal (16.2 +/-
      1.4 days vs. 11.3 +/- 0.6 days; P = .0040). Findings were similar in the subgroup
      of 46 prospectively studied patients, who included 24 Drain patients and 22 No
      drain patients. In this group, pain evaluation using a scale of 0 to 10 showed a
      mean rating of 4.2 +/- 2.6 in Drain patients and 2.7 +/- 0.4 in No-drain patients
      (P = .0062). CONCLUSIONS: Axillary node dissection can be managed with or without
      a drain. More office visits but less pain can be expected if a drain is not used.

PMID- 9607624
TI  - Detection of eIF4E gene amplification in breast cancer by competitive PCR.
AB  - BACKGROUND: Initiation factor eIF4E binds to mRNA as the initial step for protein
      translation. Overexpression of the eIF4E oncoprotein has been found in breast
      cancer but not in benign breast tissue. The objective of this study is to
      determine if eIF4E oncoprotein overexpression is associated with eIF4E gene
      amplification in breast cancer using Western blots and competitive polymerase
      chain reaction (PCR). METHODS: Unknown concentrations of DNA extracted from
      breast specimens were amplified by PCR using a set of primers spanning intron
      2/exon 3 of the eIF4E gene. In the same PCR tube, an internal control consisting
      of a known concentration of an eIF4E DNA template with 20-base pair (bp) deletion
      was used as the competitive reference standard (CRS) for competitive PCR. Gel
      electrophoresis of the PCR products was performed and the bands quantified by
      densitometry. eIF4E gene amplification was then determined relative to a
      nonamplified gene (gastrin). Using an anti-eIF4E rabbit antibody, Western blots
      were performed on benign and malignant breast specimens. Quantification was
      accomplished by developing blots with a color assay using nitro blue tetrazolium
      (NBT) and 5-bromo-4-chloro-3-indolyl phosphate (BCIP), scanned and analyzed by
      densitometry. RESULTS: Twenty-two breast specimens (14 cancer, 8 control) from
      patients were examined for eIF4E gene amplification and oncoprotein expression.
      In all fourteen specimens from stage I-III breast cancer patients, eIF4E
      overexpression was detected at 3- to 30-fold ( 16.71 +/- 7.83) elevations.
      Similarly, all 14 specimens demonstrated eIF4E gene amplification by competitive
      PCR (3.69 +/- 1.27). In the eight benign breast specimens examined, all were
      negative for eIF4E overexpression and gene amplification. CONCLUSIONS:
      Overexpression of eIF4E was associated with eIF4E gene amplification in breast
      cancer specimens. No overexpression or gene amplification was detected in benign
      breast tissues. eIF4E gene amplification may be one mechanism for eIF4E
      oncoprotein overexpression.

PMID- 9607625
TI  - Soft tissue sarcomas of the hand and foot: management and survival.
AB  - BACKGROUND: Soft tissue sarcomas of the hands and feet present a challenge for
      limb-preserving resections. METHODS: A retrospective review of 19 patients with
      sarcomas of the hand or foot was done. Wide or local excision was performed in 14
      patients (74%), and amputation in 5 patients (26%). Of the latter group, three
      amputations involved a digit or toe, and two (10%) were major amputations (one
      Syme amputation and one below-knee amputation). When the minimum surgical margin
      was narrow (1 to 2 mm), adjuvant radiation was given postoperatively (n = 4).
      RESULTS: Local recurrence was observed in four patients (21%). Two of these
      required an amputation for local control. Local recurrence was observed in one of
      four patients (25%) treated with marginal resection and radiation and three of 15
      (20%) of those with resection alone. CONCLUSIONS: A sizable percentage (37%) of
      patients with soft tissue sarcomas of the hand and foot ultimately required an
      amputation, although often the amputation was a minor one involving only a toe or
      a digit. Limb preservation was successful in the majority of patients (63%). The
      local recurrence rate was 21%, which may be improved with more frequent use of
      adjuvant therapy. The 5-year survival rate was 82%, which is better than that
      usually quoted for overall extremity soft tissue sarcomas.

PMID- 9607627
TI  - Epitrochlear lymph nodes as a site of melanoma metastasis.
AB  - BACKGROUND: The incidence of epitrochlear lymph node metastasis for patients with
      melanomas on the hand or forearm is disputed, and management guidelines for these
      nodes are unclear. METHODS: The records of 13,139 consecutive melanoma patients
      were reviewed to document the incidence of metastatic disease in epitrochlear
      nodes. The frequency of direct lymphatic drainage to epitrochlear nodes was
      determined for 109 patients with melanomas of the distal upper limb who had
      undergone preoperative lymphoscintigraphy. RESULTS: Nine of 801 patients (1.1%)
      with upper limb primary melanomas developed metastatic disease in an epitrochlear
      node, and one other patient with an occult primary tumor did so. Six of these ten
      patients underwent elective axillary node dissection at the time of surgery for
      epitrochlear node disease, and three were found to have metastatic disease in an
      axillary node. Epitrochlear node metastasis occurred in only two of 83 (2.4%)
      patients with upper extremity melanoma who underwent therapeutic axillary
      dissection. Of the 109 patients who underwent lymphoscintigraphy, four (3.7%)
      demonstrated lymphatic drainage to an epitrochlear node. CONCLUSIONS:
      Epitrochlear nodal involvement from melanoma of the distal upper extremity is
      rare, and routine epitrochlear node clearance at the time of either elective or
      therapeutic axillary dissection for upper extremity melanoma is not indicated.
      However, it is desirable to perform an axillary dissection whenever surgery for
      metastatic disease in an epitrochlear node is performed.

PMID- 9607626
TI  - In vitro and in vivo effects of photodynamic therapy on murine malignant
      melanoma.
AB  - BACKGROUND: The role of photodynamic therapy (PDT) in the treatment of malignant
      melanoma is not well defined, nor is it known whether the dark melanoma cells
      absorb the light used in PDT. METHODS:  IN VITRO STUDIES: 2 x 10(5) B16 murine
      melanoma cells were incubated with aluminum phthalocyanine (AlpcS4, 2.5 mg/kg)
      and were then subjected to photoradiation (50, 100 or 200 J/cm2). Viability was
      then assessed. In vivo studies: HISTOLOGY: C57/B1 mice received 2 x 10(5) B16
      cells subcutaneously and were randomized into study (PDT) and three control
      groups. AlpcS4 2.5 mg/kg was injected intraperitoneally and the mice were exposed
      to light (100 J/cm2). After 24 hours they were sacrificed and underwent
      autopsies. Survival: 40 mice were randomized into PDT (40 J/cm2) and control
      groups and were monitored for 50 days. Tumor growth: 40 mice were randomized into
      one control and three treatment groups (PDT on day 3, 6, or 12 after injection
      with B16 cells), and were monitored for 50 days. Temperature: Tumor temperatures
      before and at the end of PDT were recorded. RESULTS:  IN VITRO STUDIES: PDT
      caused a decrease in cell viability to 15.5 +/- 0.7%, 11.5 +/- 2.1%, and 1.5 +/-
      0.7% (at 50, 100, and 200 J/cm2, respectively; P < .001). A significant reduction
      in thymidine incorporation was noted at all energy levels. In vivo studies:
      HISTOLOGY: PDT caused massive tumor necrosis. Survival: PDT prolonged the
      survival of mice (41 +/- 13.4 days) compared to controls (15.8 +/- 3.8 days, P <
      .001). Tumor growth: 31 days after injection with B16 cells, the tumor size was
      2.6 +/- 0.3 cm in the control group and 1.6 +/- 0.2, 0.9 +/- 0.3, and 1.0 +/- 0.4
      cm in the PDT groups (days 3, 6 and 12, respectively; P < .01). Temperature: PDT
      increased skin temperature to 42.8 degrees C +/- 1.3 degrees C, 45.3 degrees C +/
      3.5 degrees C, and 51.7 degrees C +/- 2.7 degrees C at 40, 60, and 100 J/cm2,
      respectively (P < .01). CONCLUSIONS: Photodynamic therapy was found to have
      significant effects in experimental melanoma in mice. The role of PDT in human
      melanoma remains to be studied.

PMID- 9607628
TI  - Molecular oncogene markers and their significance in cutaneous malignant
      melanoma.
AB  - BACKGROUND: Oncogenes and other molecular tumor markers that predict tumor
      aggressiveness may allow individualization and optimization of surgical therapy
      of intermediate-thickness malignant melanoma. We examined the expression of
      selected markers, including the HLA-DR antigen, the heat shock protein-70 (HSP
      70), and the c-myc oncogene in primary melanoma and regional nodes and related
      these findings to metastatic potential and survival. METHODS: Forty patients with
      primary melanoma (1.5-4.0 mm) were studied, all of whom had prophylactic lymph
      node dissection and were followed for 18 months to 7 years. The primary tissue
      and nodes were examined using immunohistochemical techniques for the presence of
      HLA-DR antigen and HSP-70 protein and the expression of the c-myc oncogene.
      RESULTS: Of 40 patients, there were 23 with lesions 1 to 2.9 mm thick and 17 with
      lesions 3 to 4 mm thick. Nodal metastases were present in 25 of the 40 patients
      who had elective node dissection. HLA-DR antibody stained the primary tumor in 10
      patients (25%), but there was no correlation with survival in this group. HLA-DR
      antibody stained the stroma and cellular infiltrates surrounding the primary
      tumor in 28 of 40 patients; in this group there was a correlation of HLA-DR
      staining of the peritumoral stroma with improved survival overall. HLA-DR
      staining of the peritumoral stroma also influenced survival when patients were
      stratified by tumor thickness groups 1 to 2.9 mm and 3 to 4 mm and presence of
      nodal metastases. HSP-70 was demonstrated in the primary tumor in 25% of
      patients, who were also shown to have significantly improved survival when
      compared with those whose primary tumor did not stain with HSP-70. C-myc was
      expressed in the primary tumor in 25%, but showed no correlation with survival.
      None of these proteins correlated with or predicted the presence of nodal
      metastases. CONCLUSION: We conclude that the use of specific molecular-oncogene
      markers in intermediate-thickness primary melanoma may identify patients at high
      risk for conventional treatment failure and reduced survival who may profit from
      more aggressive surgery, adjuvant therapy, or both.

PMID- 9607629
TI  - Carcinoid tumor of the breast: treatment with breast conservation in three
      patients.
AB  - BACKGROUND: Carcinoid tumors of the breast have been described in the literature.
      The diagnosis is made by identification of typical histologic features and
      confirmed by a positive argyrophilic reaction or the presence of neurosecretory
      granules. There are several theories of the pathogenesis of carcinoid tumors in
      the breast and controversy as to whether these tumors actually originate in the
      breast ducts or are tumors that arise from neuroectodermal cells that have
      migrated to the breast ducts. Historically, treatment of carcinoid of the breast
      has been by mastectomy. METHODS: We report three cases of primary carcinoid tumor
      of the breast treated with lumpectomy and axillary node dissection. No adjuvant
      radiation or systemic treatment was administered. RESULTS: In all three cases, no
      metastases were identified in lymph nodes sampled and all patients have remained
      clinically free of recurrent disease. CONCLUSIONS: Decisions about the need for
      radiation or systemic treatment of breast carcinoid tumors depend on one's
      interpretation of the pathogenesis of this disease. Breast conservation is a
      surgical option that has not been previously reported. Larger series of carcinoid
      tumors of the breast, their treatment, and their follow-up are needed.

PMID- 9607630
TI  - Routine screening for local recurrence following breast-conserving therapy for
      cancer with dynamic contrast-enhanced magnetic resonance imaging of the breast.
AB  - BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (MRI) of the
      breast is highly sensitive for the diagnosis of primary breast malignancy. We
      investigated the clinical application of dedicated dynamic breast MR for routine
      screening for local recurrence following breast-conserving therapy. METHODS:
      Patients underwent a single dynamic MR of the breast routinely in the period 1 to
      2 years following treatment, or earlier if recurrence was suspected. A biopsy was
      performed if there was suspicion of recurrence on MR. RESULTS: One hundred and
      five patients with a median age of 58 years (range 50 to 65 years) were recruited
      for the study. Sixteen biopsies were performed and nine recurrences were
      confirmed histologically. Patients not undergoing biopsy have been followed up
      for a median of 341 days (range 168 to 451 days) following the MR. The
      sensitivity for clinical examination, mammography, examination combined with
      mammography, and MRI alone for the detection of recurrent cancer were 89%, 67%,
      100%, and 100%, respectively, and the specificity was 76%, 85%, 67%, and 93%.
      CONCLUSION: Combined clinical examination and mammography are as sensitive as
      dedicated dynamic MR of the breast for the detection of locoregional recurrence,
      but breast MRI is associated with a far greater specificity. Therefore, dedicated
      dynamic breast MRI should be used when there is clinical or mammographic
      suspicion of recurrence to confirm or refute its presence.

PMID- 9607631
TI  - Regulation of macrophage production of vascular endothelial growth factor (VEGF)
      by hypoxia and transforming growth factor beta-1.
AB  - BACKGROUND: Breast tumors contain high numbers of infiltrating macrophages. The
      role and function of these cells within the tumor remain unclear, but a number of
      studies have found an association between poor prognosis and macrophage content
      in human breast cancer. Both hypoxia and TGFbeta-1 have been shown to regulate
      VEGF in other cell types. We hypothesized that breast tumor-associated
      macrophages produce VEGF and that macrophage production of this factor is
      regulated by both hypoxia and TGFbeta-1. METHODS: Paraffin-embedded breast tumor
      sections were stained immunohistochemically with anti-VEGF, anti-CD68, and anti
      cytokeratin. Monocytes were matured for 3 days in 20% autologous plasma and
      activated with 1000 U/mL interferon-gamma for 24 hours. Supernatants were assayed
      for VEGF protein by ELISA. Total RNA was isolated from cells and reverse
      transcribed to cDNA, which was used as a template in PCR reactions for VEGF and
      beta-actin. RESULTS: Both tumor cells and tumor macrophages produce VEGF in human
      breast tumors. Hypoxia increases VEGF protein and mRNA levels in monocyte-derived
      macrophages, whereas TGFbeta-1 increases VEGF protein but not mRNA under hypoxic
      growth conditions. CONCLUSIONS: Breast tumor-associated macrophages may
      contribute to the angiogenic activity of human breast tumors by producing VEGF.
      Macrophage production of VEGF is upregulated by hypoxia and TGFbeta-1, both of
      which occur in the tumor environment. Macrophage production of VEGF is regulated
      at both the mRNA and protein levels.

PMID- 9607632
TI  - Effect of IL-6 overexpression on the metastatic potential of rat hepatocellular
      carcinoma cells.
AB  - BACKGROUND: Previous studies demonstrated that excess IL-6 production correlated
      with the metastatic potential of rat hepatocellular carcinoma cells. In the work
      reported here a retroviral construct containing the gene for murine IL-6 was
      introduced into otherwise nonmetastatic tumor cells to directly determine the
      effect of IL-6 overexpression on tumor metastatic potential. METHODS: The clonal
      cell lines 1682.C.2.9.L0 (L0, poorly metastatic) and 1682.C.2.9.L10 (L10, highly
      metastatic) were selected from a parental hepatocellular carcinoma induced in ACI
      rats by feeding an ethionine-containing diet. Viral supernatant was used to
      infect the PA317 amphotropic cell line, and retrovirus produced from these cells
      infected the poorly metastatic L0 hepatocellular carcinoma cell line. Neomycin
      resistant cells were selected in G418 and designated L0-IL-6. RESULTS: As
      determined by bioassay, L0 cells produce 10 +/- 1.2 U/mL IL-6 in culture, whereas
      L10 cells release 95 +/- 11 U/mL (P < 0.01, Student's t-test). Retroviral
      mediated IL-6 gene transfer resulted in the production of 1266 +/- 48 U/mL IL-6
      by L0-IL-6 cells under identical culture conditions. When an inoculum of 5 x
      10(6) cells is injected subcutaneously, both L0 and L10 cell lines result in
      primary tumors with equivalent rates of growth; only L10 cells metastasize to the
      lung, however. A similar inoculation of L0-IL-6 cells produced local tumors in
      all 24 animals tested. Interestingly, 15 of 24 (62%) animals presented with
      metastatic nodules in the abdominal cavity, whereas no such tumors were found in
      animals receiving L10 cells. CONCLUSION: Overexpression of IL-6 increases
      metastatic potential of tumor cells, with preferential metastases to the
      abdominal cavity when compared with tumor cells elaborating endogenous IL-6.

PMID- 9607633
TI  - Flow cytometric measurement of mitochondrial mass and function: a novel method
      for assessing chemoresistance.
AB  - BACKGROUND: Chemotherapeutic agents induce apoptosis in cancer cells. Drugs
      failing to induce apoptosis are likely to have decreased clinical efficacy. We
      hypothesize that (1) chemotherapeutic agents induce mitochondrial changes and
      apoptosis through mechanisms associated with reactive oxidant species production;
      (2) the anti-apoptotic protein Bcl-2 prevents drug-induced mitochondrial changes,
      reactive oxygen species (ROS) production, and apoptosis; and (3) the assay of
      drug-induced mitochondrial changes can reflect drug-specific chemoresistance in a
      given cancer cell line. METHODS: A stable Bcl-2 transfectant of the Bcl-2
      negative breast cancer cell line SKBr3 was created (SKBr3/Bcl2-2). Both SKBr3 and
      SKBr3/Bcl2-2 cells were treated with Herbimycin A (300 ng/mL) or vehicle (1%
      DMSO). Cell cycle changes were assessed by BRDU staining. Apoptosis was
      determined by electron microscopy, TUNEL (TdT-mediated dUTP-biotin nick end
      labeling) staining, and diphenylamine assay of DNA fragmentation. Changes in
      mitochondrial mass and transmembrane potential (deltapsi(m)) were assessed by
      flow cytometric assessment of JC-1 fluorescence. Reactive oxygen species
      production was measured by 2',7'-dichlorodihydrofluorescein diacetate (DCFH)
      fluorescence. RESULTS: Both SKBr3 and SKBr3/Bcl2-2 cells show cell cycle arrest
      after Herbimycin treatment. However, SKBr3 cells, but not SKBr3/Bcl2-2 cells,
      undergo apoptosis. Herbimycin-treated SKBr3 cells show increased mitochondrial
      mass (JC-1 green fluorescence), with no corresponding increase in deltapsi(m) (JC
      1 red fluorescence). By contrast, Herbimycin-treated SKBr3/Bcl2-2 cells show no
      change in mitochondrial mass or deltapsi(m). Similarly, drug-treated SKBr3 cells,
      but not SKBr3/Bcl2-2 cells, demonstrate increased reactive oxygen species (ROS)
      production concomitant with the development of apoptosis. CONCLUSION: SKBr3 cells
      undergoing apoptosis demonstrate mitochondrial changes associated with ROS
      production. Bcl-2 transfection prevents these changes because it prevents
      apoptosis and induces chemoresistance to Herbimycin in SKBr3. Flow cytometric
      measurement of drug induced mitochondrial changes and ROS production may
      facilitate in vitro assessment of chemosensitivity or chemoresistance in breast
      cancer.

PMID- 9607635
TI  - Stem cells transplantation--a cure for autoimmune diseases.

PMID- 9607634
TI  - New insights into the pathogenesis of anti-Ro antibody associated congenital
      complete heart block.

PMID- 9607636
TI  - Induction of in vitro heart block is not restricted to affinity purified anti-52
      kDa Ro/SSA antibody from mothers of children with neonatal lupus.
AB  - The ability of affinity purified anti-52 kDa Ro/SSA antibody from patients
      without obstetric history of neonatal lupus to cause heart block using an
      experimental model was investigated. IgG-enriched fractions from sera of 20
      systemic lupus erythematosus (SLE) and one Sjogren's syndrome (SS) all positives
      for anti-Ro/SSA antibodies as detected by CIE, were perfused on isolated whole
      rabbit hearts. Only six (29%) samples induced A-V block, five of them presenting
      low anti-Ro/SSA titre. All of them recognized the 52 kDa isoform on ELISA whereas
      only one had a concomitant binding to the 60 kDa protein. Moreover, affinity
      purified antibodies from two sera previously known to induce A-V block were
      obtained by affinity chromatography using a column containing the full-length 52
      kDa Ro/SSA fusion protein. Paired eluate and effluent devoid of anti-52 kDa
      activity from the same patient were individually perfused in whole hearts. The
      ability to cause cardiac blockade was restricted to the affinity anti-52 kDa
      eluates. In addition, anti-52 kDa eluates from three IgG fractions that primarily
      failed to induce blockade remained ineffective. The present study has added to
      our knowledge that affinity anti-52 kDa Ro/SSA antibodies from mothers with
      healthy infants are capable of causing in vitro cardiac conduction disturbances.
      A prospective follow up of these patients will better delineate the clinical
      usefulness of this experimental model.

PMID- 9607637
TI  - 4-Aminoquinoline antimalarials enhance UV-B induced c-jun transcriptional
      activation.
AB  - Previous work has documented that the earliest observable response in mammalian
      cells following ultraviolet (UV) irradiation is the activation of plasma membrane
      associated Src tyrosine kinases. These molecules then trigger a signalling
      cascade that results in activation of the transcription factor AP-1 which
      subsequently transactivates the early immediate genes including c-jun. This
      pathway has been postulated to play a protective role against UV damage. As
      aminoquinoline antimalarials such as chloroquine are known to downregulate
      several photoinduced cutaneous disorders including LE-specific skin disease, we
      asked whether chloroquine might be capable of modulating this early limb of the
      UV light response. A431 cells (a human epidermal keratinocyte cell line) that had
      been transfected with a c-jun luciferase reporter gene construct were then
      treated with physiologically relevant concentrations of chloroquine followed by
      exposure to 0-125 J/m2 of UV-B from a bank of unfiltered FS20 lamps. Chloroquine
      pretreatment resulted in a dose-dependent increase in luciferase activity in
      permanently transfected A431 cells (luciferase activity was increased by 45% at
      2.5 x 10(-5) M chloroquine and 125 J/m2 of UV-B). Hydroxychloroquine pretreatment
      also resulted in an increase in luciferase activity. Primaquine, an 8
      aminoquinoline, did not influence the UV-B induced c-jun activity. Furthermore,
      chloroquine did not have a similar impact on HSP-70 gene activity during heat
      shock. These studies suggest that the beneficial effect of the 4-aminoquinoline
      antimalarials in various photodermatoses including cutaneous LE might result in
      part from the capacity of these drugs to enhance the protective early limb of the
      UV response.

PMID- 9607638
TI  - Renal expression of IL-6 and TNFalpha genes in lupus nephritis.
AB  - These studies were carried out to examine the presence of the inflammatory
      cytokines IL-6 and TNFalpha in kidneys of patients with lupus nephritis as an
      indicator of their possible role in its pathogenesis. A total of 19 kidney
      biopsies from patients with type III or IV lupus nephritis were processed by
      direct immunofluorescence using monoclonal anti-IL-6 and TNFalpha antibodies.
      Local expression of these genes was demonstrated both by in situ hybridization
      and by reverse transcriptase-PCR amplification of total RNA isolated from kidney
      tissue. Fifty-two percent of the biopsies exhibited IL-6 and TNFalpha deposited
      along the glomeruli and tubules; in situ expression of these cytokines was
      demonstrated in 6 biopsies with type IV, and 1 with type III nephritis.
      Inflammatory cytokines are actively synthesized in the kidneys of patients with
      lupus nephritis and therefore, may play a role in its pathogenesis.

PMID- 9607639
TI  - Survival analysis of 306 European Spanish patients with systemic lupus
      erythematosus.
AB  - OBJECTIVE: To describe survival of lupus in South European Spanish patients.
      PATIENTS AND METHODS: Observational study of all SLE Spanish patients seen at
      three University Hospitals between 1975 and 1993. The charts of all patients were
      retrospectively reviewed. Sixty-four clinic and laboratory variables were
      extracted from charts. Univariate analysis, multivariate Cox proportional hazard
      regression analysis, actuarial life tables and multiple logistic regression
      analysis were used to calculate survival probability and identify variables
      associated with survival. RESULTS: Three hundred and six (275 female and 31 male)
      patients were identified. Their mean age at diagnosis was 31.9 years (range 4 to
      85). The mean duration of followup was 79 (1-126) months. Thirty-one patients
      died. The most common cause of death was infection (29%). Five, 10 and 15 years'
      survival rate was 90%+/-0.0158, 85%+/-0.0262 and 80%+/-0.0413, respectively. Log
      rank analysis showed that male sex, proteinuria and nephropathy at diagnosis were
      associated with poor survival. By univariate and multivariate analysis male
      gender, nephropathy and CNS involvement were associated with worse survival.
      CONCLUSION: In SLE patients from Spain, rate of survival is similar to other
      Caucasian patients, and better than other ethnic groups of Spanish ancestry.
      Other factors rather than genetic factors could explain our findings.

PMID- 9607640
TI  - Naturally occurring anti-idiotypic antibodies reactive with anti-DNA antibodies
      in systemic lupus erythematosus.
AB  - The levels of 'putative' anti-idiotypic antibodies reactive with F(ab')2
      fragments of affinity purified DNA binding antibodies from five SLE patients were
      measured in the serum of active and inactive systemic lupus erythematosus (SLE)
      patients, their relatives, spouses and healthy non-related individuals. Serum
      anti-idiotypic antibodies of the IgG isotype could be detected in the serum of
      8/15 inactive SLE patients, 3/19 active SLE patients, 17/27 SLE relatives, 1/4
      SLE spouses and 6/32 healthy non-related individuals. When the serum
      immunoglobulins from the individuals in each group were separated into IgG and
      IgM antibody fractions and analysed, a significant increase in levels of IgG anti
      idiotypic reactivity were found in healthy individuals (16/32), whilst no
      significant increase in IgG anti-idiotypic antibodies were detected in SLE
      patients, SLE relatives and SLE spouses. Comparatively few individuals tested
      showed detectable levels of IgM anti-idiotypic antibodies. These results
      demonstrate that anti-idiotypic antibodies reactive with anti-DNA antibodies are
      detectable in the serum of SLE patients, SLE relatives, SLE spouses and healthy
      individuals, and are predominantly of the IgG isotype. The increased frequency of
      IgG anti-idiotypic antibodies after separation from serum IgM antibodies infers
      that anti-idiotypic activity of some IgG immunoglobulins in the sera of healthy
      individuals may be masked by the presence of IgM antibodies in the serum.

PMID- 9607641
TI  - Familial coexistence of primary antiphospholipid syndrome and factor VLeiden.
AB  - The antiphospholipid syndrome (APS) is an autoimmune thrombophilic disorder in
      which thromboembolism and thrombocytopenia occur. The antiphospholipid antibodies
      in these patients may cause acquired activated protein C resistance, whereas
      hereditary activated protein C resistance results from a common single point
      mutation in coagulation factor V (factor VLeiden). In a family of 11 members with
      4 normal subjects, autoimmune thrombocytopenia was documented in 6 patients.
      Three out of these were found to have thrombocytopenia associated with primary
      APS. In addition, these 3 subjects were also heterozygous for the factor VLeiden.
      Only in this group of individuals did life threatening thromboembolic
      complications occur, while other thrombocytopenic family members showed no
      thrombotic manifestations. Genetic studies revealed no linkage between APS and
      HLA class II alleles. Taken together, we present a family with autoimmune
      thrombocytopenia, which is associated with primary APS in at least 50% of
      thrombocytopenic individuals. The coexistence of both APS and factor VLeiden in
      thrombocytopenic subjects, led to an increased number of thrombotic events,
      suggesting a critical role of combined acquired and hereditary activated protein
      C resistance in the development of thrombosis in this family. Since no
      association between APS and specific HLA groups was found, other underlying risk
      factors for the development of APS must be considered.

PMID- 9607642
TI  - Clinical correlates, serum autoantibodies and the role of the major
      histocompatibility complex in French Canadian and non-French Canadian Caucasians
      with SLE.
AB  - OBJECTIVE: To investigate the predisposing role of major histocompatibility
      complex (MHC) genes to autoantibody production and clinical manifestations
      comparing French Canadian and Non-French Canadian Caucasians with systemic lupus
      erythematosus (SLE) METHODS: Ninety-one Caucasian patients with SLE were studied.
      Clinical manifestations, autoantibody expression and HLA-A, B, (serology), DR, DQ
      and C4A gene deletion (restriction fragment length polymorphism [RFLP] typing)
      were determined. RESULTS: Photosensitivity was present in all SLE subjects with
      anti-Ro antibodies (P=0.001, RR=13.1, CI=1.8, 564). Photosensitivity was further
      associated with the HLA-A1, C4A gene deletion haplotype. More strikingly, C4A
      gene deletion was associated with anti-Ro (P=0.008, RR=4.6, CI=1.4, 16.2) and
      anti-La (P=0.02, RR=11.7, CI=1.4, 549) autoantibodies. This relationship was also
      significant for anti-Ro antibody in the French Canadian patients (P=0.01,
      RR=21.3, CI=1.7, 105.3). In contrast, anti-dsDNA autoantibodies were negatively
      associated with photosensitivity (P=0.02, RR=0.3, CI=0.07, 0.8) and correlated
      with HLA-DR15 (P=0.006, RR=4.2, CI=1.5, 12.8) and Dw2 (P=0.009, RR=3.9, CI=1.4,
      11.9). CONCLUSION: C4A gene deletion has a previously unrecognized powerful
      association with anti-Ro and anti-La autoantibodies. These results support the
      concept of divergent MHC gene associations with autoantibody expression and
      emphasize the influence of ethnicity on the immunogenetic study of SLE.

PMID- 9607643
TI  - Dietary polyunsaturated fatty acids decrease anti-dsDNA and anti-cardiolipin
      antibodies production in idiotype induced mouse model of systemic lupus
      erythematosus.
AB  - OBJECTIVE: To examine the effect of diets with different polyunsaturated fatty
      acid contents, including linseed oil which contains 70% omega-3 fatty acids, on
      autoantibody production in idiotype induced mouse model of systemic lupus
      erythematosus (SLE). METHODS: Five different fats were fed to mice with induced
      SLE and antibody titers to anti-DNA and anti-cardiolipin were determined and
      histological examination of kidneys were carried out. RESULTS: SLE mice fed
      linseed oil showed lower titers of antibodies to DNA and to cardiolipin and less
      severe kidney damage than mice fed other diets, including fish oil. CONCLUSION:
      Use of linseed oil may attenuate the severity of SLE and this diet may be
      recommended for other auto-immune diseases as well.

PMID- 9607644
TI  - Serological markers in Arabs with lupus nephritis.
AB  - The aim of this study was to characterize the autoantibody profile of Arabs with
      lupus nephritis (LN). Therefore, the records of 42 Arabs with classical systemic
      lupus erythematosus (SLE) were reviewed. Twenty one (50%) with LN and 21 without.
      Most patients with LN have developed their nephropathy within the first five
      years of the disease. Only C3 hypocomplementemia achieved statistically
      significant correlation in nephritic patients and anti ribonucleoprotein (RNP)
      antibodies in non-nephritic patients. The difference in anti double stranded DNA
      (dsDNA) antibodies was insignificant (P=0.107), as both groups had markedly high
      prevalence of these antibodies. In addition, there was no significant negative
      association between detectable rheumatoid factor (RI) and patients with LN. We
      also examined the spectrum of specific entities of antibodies that had previously
      been reported in association with LN in other series (anti Smith (Sm), RNP and SS
      A without anti SS-B, anti SS-A and SS-B, anti RNP and Smith, anti RNP and dsDNA
      and anti RNP and SS-A antibodies). None has shown any correlation with renal
      disease, P=1.00, P=0.591, P=0.613, P=0.195 and P=0.148, respectively. In
      conclusion, the study demonstrates that Arab patients with LN do not exhibit a
      distinctive serological profile, nonetheless it provides useful information to
      studies of SLE in different ethnic or racial groups.

PMID- 9607646
TI  - Basaloid follicular hamartoma, total body hair loss and SLE.
AB  - We describe a patient with systemic lupus erythematosus (SLE) and
      antiphospholipid antibody syndrome (APLS) who developed a plaque-like lesion
      around the mouth and lost all body hair. Biopsies of the circumoral lesion and
      scalp, were originally reported as containing extensive basal cell carcinoma, but
      on review, both showed the typical appearance of a benign malformation of the
      hair follicle known as basaloid follicular hamartoma. Regrowth of hair and
      partial resolution of the peri-oral plaque occurred with more aggressive
      treatment of her SLE, but the basaloid follicular hamartomas in her scalp skin
      persisted. There is a known, but rare, association between this pattern of
      basaloid follicular hamartoma, alopecia and myasthenia gravis, but only two cases
      have been described in association with SLE and none with APLS.

PMID- 9607645
TI  - Young onset of primary Sjogren's syndrome: clinical and immunological
      characteristics.
AB  - The objective of our study was to determine the clinical and immunological
      characteristics of primary Sjogren's syndrome (SS) in patients with a young onset
      of the disease. We included 144 consecutive patients (134 female and 10 male;
      mean age at onset 53 y; range 20-87 y) visited in our Units. All patients were
      white and fulfilled four or more of the diagnostic criteria for SS, proposed by
      the European Community Study Group in 1993. Disease onset was determined on the
      basis of the appearance of symptoms strongly suggestive of SS. In 13 (9%)
      patients, disease onset occurred before the age of 35. All were female and the
      disease onset occurred between 20-34 y (mean, 28 y). When compared with patients
      with older onset, patients with a young onset of the primary SS presented a
      higher prevalence of lymphadenopathy (54% vs 6%, P < 0.001), rheumatoid factor
      (70% vs 39%, P=0.034), anti-Ro/SS-A antibodies (70% vs 28%, P=0.004) and
      monoclonal immunoglobulins (23% vs 4%, P=0.02) in their sera. From the initial
      diagnosis of SS, three patients with a young-onset of the primary SS have
      developed lymphoproliferative disease at the time of the study, compared with one
      patient of the older-onset group (23% vs 1%, P=0.002). Our study shows several
      differences between younger and older onset patients, including a higher
      incidence of lymphomas in the younger, thus conferring to the age at onset of the
      disease a prognostic value.

PMID- 9607647
TI  - Evidence for immune system involvement in reflex sympathetic dystrophy.
AB  - Skin biopsies from patients with reflex sympathetic dystrophy were immunostained
      using a variety of antisera. An incidental finding with S100 staining was the
      presence of numerous Langerhans cells in the epidermis. All patients had
      significant pain at the time of biopsy, and all had symptoms refractory to
      treatment. The potential implications of this finding are discussed.

PMID- 9607648
TI  - The sensitivity and specificity of tests for carpal tunnel syndrome vary with the
      comparison subjects.
AB  - The performance of a variety of common office-based clinical tests for detection
      of carpal tunnel syndrome (CTS) was assessed in 119 subjects with and without
      electrophysiological evidence of CTS. Symptoms compatible with CTS and
      electrophysiological tests positive for median mononeuropathy at the wrist were
      observed in 57 hands, symptoms compatible with CTS and normal
      electrophysiological test results were observed in 58 hands, and no symptoms
      compatible with CTS and normal electrophysiological test results were observed in
      123 hands. For all the diagnostic tests studied, the proportion of subjects who
      had a false positive clinical test result was much higher in the
      electrophysiologically normal subjects who had CTS compatible hand symptoms than
      in the electrophysiologically normal subjects who were asymptomatic. These
      results suggest that many studies that have evaluated diagnostic tests for CTS
      have produced falsely optimistic estimates of the test's performance because of
      their use of asymptomatic comparison subjects.

PMID- 9607650
TI  - Normal digital contribution to grip strength assessed by a computerized digital
      dynamometer.
AB  - A computerized digital dynamometer was used to assess the contribution of
      individual fingers to total grip strength in 100 hands from 50 randomly selected
      healthy subjects. The dynamometer simultaneously recorded force data from each
      digit (index, long, ring, and small) and cumulative grip directly to a laptop
      computer. The percentage contribution of each finger force to total grip force
      was calculated at three successive handle sizes for dominant and non-dominant
      hands. Individual digital contributions to total grip strength were approximately
      25%, 35%, 26% and 15% for the index, long, ring, and small fingers respectively.
      This pattern was consistent irrespective of handle size, hand dominance, and grip
      strength.

PMID- 9607649
TI  - The outcome of tendon transfers for C6-spared quadriplegics.
AB  - The purpose of this study was to review retrospectively and evaluate a uniform
      group of C6-spared quadriplegics who had similar surgical procedures. Eight
      patients undergoing 12 procedures were reviewed at an average of 3.8 years follow
      up. There were three bilateral procedures. All patients had extensor carpi
      radialis longus to flexor digitorum profundus and brachioradialis to flexor
      pollicis longus transfers to improve grip strength and key pinch. All patients
      reported subjective improvements in quality of life, activities of daily living
      and patient-centred goals. There were six excellent and two good results.
      Objective improvements included mild improvements in key pinch and grip strength.

PMID- 9607651
TI  - The innervation pattern of the radial nerve at the elbow and in the forearm.
AB  - Sixty paired cadaver forearms were dissected to examine the distribution of the
      radial nerve branches to the muscles at the elbow and forearm. Emphasis was
      placed on the innervation of the extensor carpi radialis brevis and the supinator
      muscles because of discrepancies in the literature concerning these muscles. The
      most common branching pattern (from proximal to distal) was to brachioradialis,
      extensor carpi radialis longus, superficial sensory, extensor carpi radialis
      brevis, supinator, extensor digitorum/extensor carpi ulnaris, extensor digiti
      minimi, abductor pollicis longus, extensor pollicis brevis, extensor pollicis
      longus and extensor indicis. The branch to extensor digitorum and extensor carpi
      ulnaris came off as a common stem often with the branch to extensor digiti
      minimi. The branch to the ECRB muscle was noted to arise from the posterior
      interosseous nerve in 45%, superficial sensory nerve in 25% and at the
      bifurcation of the posterior interosseous and superficial sensory nerves in 30%
      of specimens. The supinator had an average of 2.3 branches from the posterior
      interosseous nerve (range 1-6). The branches to the supinator showed a wide
      variability proximal to and within the supinator.

PMID- 9607652
TI  - The flexor pollicis longus and its relation to the anterior and posterior
      interosseous nerves.
AB  - Sixty paired cadaver upper extremities were dissected to study the anatomy of the
      flexor pollicis longus in the forearm and its relation to the median and anterior
      interosseous nerves. An accessory head was noted in 33 (55%) of 60 specimens. The
      accessory head was noted to pass anterior to the anterior interosseous nerve in
      all specimens. The accessory head was noted to pass posterior to the median nerve
      in 57 specimens, and anterior to the nerve in three. Tendon or muscle anomalies
      were noted in eight specimens (13%), seven of which involved an anomalous
      attachment between the FPL and the flexor digitorum profundus of the index.

PMID- 9607653
TI  - Ulnar styloid malunion with dislocation of the distal radioulnar joint.
AB  - Four patients with dorsal dislocation of the distal radioulnar joint and ulnar
      styloid malunion had corrective osteotomy of the ulnar styloid. Dislocation of
      the distal radioulnar joint was reduced in three of four patients. Subluxation
      persisted in the remaining patient. Wrist function improved in all patients.
      These results support the contention that a displaced ulnar styloid fracture with
      distal radioulnar joint dislocation should be reduced and internally fixed.
      Corrective osteotomy is recommended for malunion of the ulnar styloid associated
      with dislocation of the distal radioulnar joint.

PMID- 9607654
TI  - Avulsion fracture at the fovea of the ulna. A report of two cases.
AB  - We report two cases of avulsion fractures at the fovea of the ulna. This injury
      is caused by a strong distraction force which avulses the insertion of the
      triangular ligament at the fovea of the ulna. This injury can be classed as an
      injury to the triangular fibrocartilage complex.

PMID- 9607655
TI  - The interosseous membrane and its influence on the distal radioulnar joint. An
      anatomical investigation of the distal tract.
AB  - From the interosseous membrane of the forearm a tract extends to the dorsal
      capsule of the distal radioulnar joint. The structure and function of this tract
      have been investigated. The tract originates from the radius 22 mm proximal to
      the distal dorsal corner of the sigmoid notch. Central fibres are attached there
      with fibrous cartilage and superficial bundles mix with the periosteum. The tract
      is 8 mm wide, 31 mm long and 1 mm thick. Distally it inserts at the capsule of
      the distal radioulnar joint between the tendon sheaths of extensor digiti minimi
      and extensor carpi ulnaris. Deep fibres insert directly at the triangular
      fibrocartilage. The tract of the interosseous membrane is taut in pronation and
      loose in supination. It strengthens the dorsal capsule of the distal radioulnar
      joint. During pronation the tract protects the ulnar head in a sling. Its
      attachment at the triangular fibrocartilage influences the distal radioulnar
      joint. Its insertion at the triangular fibrocartilage and the support of the
      weakest part of the dorsal capsule are of interest.

PMID- 9607656
TI  - Evaluation of five different incisions for correction of radial dysplasia.
AB  - The complications of the five different incisions used for centralization from
      1970 to 1996 were evaluated. In five cases access was by an S- shaped incision,
      in one with a transposition flap. Sixteen centralizations were done using a
      radial Z-plasty in combination with an ulnar excision and four by using two
      opposite Z- plasties, preserving wrist mobility as much as possible. In 1995 and
      1996 a bilobed flap was used in seven cases. No complications occurred with the
      primary procedures prior to 1995. In all seven cases where the bilobed flap was
      used venous congestion was seen. In four out of these seven superficial necrosis
      of parts of the flaps occurred. In all cases though wound healing occurred
      spontaneously by delayed primary healing after the standard 8 weeks of cast
      immobilization.

PMID- 9607657
TI  - Distraction lengthening of the ulna in radial club hand using the Ilizarov
      technique.
AB  - Six children with radial club hand had distraction lengthening of the ulna using
      the Ilizarov technique at the mean age of 10 years. The mean lengthening achieved
      was 4.7 cm (46% of original ulna length). Complications included nocturnal pain,
      pin track infection and callus fracture or delayed union. Distraction lengthening
      of the ulna can enhance the ability to perform normal activities of daily living,
      such as reaching the perineum or driving a car, but complications are extremely
      common. The high rate of callus fracture in this series reinforces the need for
      regular radiographic review during distraction and suggests that after
      distraction it may take more than 4 weeks for satisfactory callus consolidation
      before removal of the fixator.

PMID- 9607658
TI  - Ilizarov distraction-lengthening in congenital anomalies of the upper limb.
AB  - Nine patients underwent Ilizarov distraction-lengthening for congenital
      anomalies. All were late cases and had undergone other procedures. In five radial
      club hand patients with very short forearms, we achieved an average 5.8 cm
      increase in length with each distraction cycle. In two patients with
      symbrachydactyly of the cleft hand type, we achieved pinch grip between a radial
      and an ulnar digit by lengthening the short ray. Another case of the monodactyly
      type in which we tried to lengthen three transplanted proximal toe phalanges
      ended in failure. A soft tissue distraction was attempted in a case of
      camptodactyly but failed. We report the problems we encountered and suggest some
      solutions.

PMID- 9607659
TI  - A regional audit of hand and wrist injuries. A study of 4873 injuries.
AB  - This study reports the characteristics, causes and disposal of isolated injuries
      to the hand and wrist presenting to six accident and emergency departments over a
      period of 4 months. The rate of isolated injury to the hand or wrist was 6.6%.
      The male: female ratio was 2.2: 1, with the mean age for injury being 26.4 years
      in men and 29.2 years in women. The modal age group for injury was 21-25 years in
      men and 11-15 years in women. The right and left hand were injured almost
      equally. The dominant hand was more commonly injured although this was influenced
      by the cause of injury: 16.3% were caused by a fall; 15% by sport; and 7% were
      work/machinery related. 13.3% were referred to specialities for further
      treatment.

PMID- 9607660
TI  - Proximal scaphoid costo-osteochondral replacement arthroplasty.
AB  - Deficiency of the proximal pole of the scaphoid due to fracture or necrosis was
      treated by costo-osteochondral replacement arthroplasty using rib bone/cartilage
      autografts in 22 patients who were followed prospectively and assessed at a
      median 24 month follow-up (range, 12-72 months). Improvement of wrist function
      occurred in all patients with increased motion, improved grip strength and less
      pain. The average modified Green and O'Brien Wrist Function Score improved from
      53 out of 100 preoperatively to 80 at the most recent review. All patients were
      graded fair or poor at initial review and all but three improved to good or
      excellent at the most recent assessment. Despite the absence of the scapholunate
      ligament, carpal alignment did not deteriorate in any patient and there were no
      graft non-unions or significant complications. In the short and medium term a
      costo-osteochondral autograft can satisfactorily restore mechanical integrity of
      the scaphoid proximal pole and maintain wrist motion while avoiding the potential
      complications of alternative replacement arthroplasty techniques.

PMID- 9607661
TI  - A biomechanical analysis of intrascaphoid compression using the Herbert scaphoid
      screw system. An in vitro cadaveric study.
AB  - The purpose of this study was to evaluate the compressive capabilities of the
      Herbert scaphoid screw system. A transverse osteotomy was performed at the waist
      of eight scaphoids removing a 3 mm wafer of bone. A custom-designed load washer
      was inserted within this defect to measure intrascaphoid compression during Huene
      guide application, during screw insertion, after screw insertion and after guide
      release. The intrascaphoid compression was noted to peak during screw insertion;
      however it dramatically decreased without any clinical subjective evidence of
      decreased insertional torque by the surgeon. The average final compression as a
      percentage of maximal compression was 38 (SD 26) %.

PMID- 9607662
TI  - Treatment of painful neuromas of the hand and wrist by relocation into the
      pronator quadratus muscle.
AB  - Thirteen painful end-neuromas of nerves of the palm and the dorsum of the hand
      were treated by resection of the neuroma and relocation of the nerve ends into
      the pronator quadratus muscle proximal to the wrist in ten patients. The
      effectiveness of this treatment was assessed by measurement of changes in level
      of spontaneous pain, pain on pressure, pain on movement and hyperaesthesia at the
      original site and at the site to which the nerve was relocated. Subjective
      comments on changes of hand function and ability to return to work were also
      recorded. All ten patients reported total relief or marked improvement in each of
      the four modalities of pain assessed. In the five patients in whom the neuromas
      were the only significant cause of hand dysfunction, there was sufficient
      improvement in hand function to allow the patients to return to work. In this
      series, the pronator quardratus muscle has proved a suitable site for relocation
      of sensory nerve ends after resection of painful neuromas in the proximal part of
      the hand and wrist.

PMID- 9607663
TI  - Vein implantation for treatment of painful cutaneous neuromas. A preliminary
      report.
AB  - Based on the theory that recurrent neuroma formation can be prevented if the cut
      nerve end is implanted into the lumen of a vein, 14 patients have been treated by
      neuroma excision followed by proximal vein implantation over the last 5 years.
      Thirteen patients reported dramatic pain relief following surgery, and this was
      sustained in all but one case. Both failures were re-explored, when it was found
      that the nerve had pulled out of the vein, leading to recurrent neuroma
      formation. Both cases were revised successfully using the same technique. With a
      mean follow-up of 15 months, 11 patients remain symptom-free, whilst three have
      minor residual symptoms which are not severe enough to require further surgery.

PMID- 9607664
TI  - The prognostic value of concurrent phrenic nerve palsy in newborn children with
      Erb's palsy.
AB  - The prognostic value of concurrent phrenic nerve palsy in newborn babies with
      Erb's palsy was investigated. The records of 191 babies with Erb's palsy were
      reviewed retrospectively at two institutions. Poor spontaneous return of the
      motor function of the limb was found for infants both with and without concurrent
      phrenic nerve palsy. Concurrent phrenic nerve palsy in newborn babies with Erb's
      palsy has no prognostic value in predicting spontaneous motor recovery of the
      limb.

PMID- 9607665
TI  - Sternomastoid muscle flap for closure of a dural fistula after a brachial plexus
      injury.

PMID- 9607666
TI  - Mechanical strengths of tendon sutures. An in vitro comparative study of six
      techniques.
AB  - A comparative study of six tendon suturing techniques (1. Modified Kessler +
      simple epitendinous running suture; 2. Modified Kessler + Halsted epitendinous
      suture; 3. "Six strand" suture; 4. "Interlocking" suture; 5. "Cross stitch"
      suture; 6. simple epitendinous running suture) was carried out by evaluating
      strength in relation to the beginning of separation between the tendon stumps, a
      3 mm separation and rupture in porcine flexor tendons. The technique most
      resistant to initial separation was the modified Kessler + Halsted epitendinous
      suture followed by the "Six strand" suture. The "Six strand" suture was the most
      resistant to the 3 mm separation and rupture followed by the modified Kessler +
      Halsted epitendinous suture. Despite the greater resistance to rupture of the
      "Six strand" technique, we conclude that modified Kessler + Halsted epitendinous
      suture showed the best overall performance and was easier to use.

PMID- 9607667
TI  - The chiasma of the flexor digitorum superficialis tendon.
AB  - Forty cadaver hands (160 fingers) were dissected to study the morphology and
      variations of the chiasma of the flexor digitorum superficialis tendon. Ten types
      of chiasma were noted. One chiasma did not fit into any of the patterns. The long
      and ring fingers had a very similar distribution of types of chiasma but the
      index and small both had different patterns. The length of chiasma showed a
      marked variability which appeared to be independent of phalangeal length.

PMID- 9607668
TI  - Colour Doppler analysis of tendon and muscle movements.
AB  - We have examined and successfully visualized active and passive movement of
      tendons and muscles using colour Doppler ultrasound. This preliminary study
      suggests that colour Doppler may be very useful to examine the movements of
      tendons and muscles.

PMID- 9607669
TI  - Finger flexion sign for ulnar neuropathy.
AB  - We report a diagnostic sign of ulnar neuropathy. Function of the interossei is
      tested by asking the patient to hold a sheet of paper between the middle and ring
      fingers, by adducting the fingers while the examiner pulls it firmly away. The
      metacarpophalangeal joints will flex more on the affected side as the flexor
      tendons are recruited. This test can easily detect muscle weakness in the early
      stage of ulnar neuropathy, and is produced by a similar mechanism to that of
      Froment's sign.

PMID- 9607670
TI  - Ulnar nerve compression in Guyon's canal due to a haemangioma of the ulnar
      artery.

PMID- 9607671
TI  - The treatment of fractures of the ring and little metacarpal necks. A prospective
      randomized study of three different types of treatment.
AB  - A total of 105 patients with fracture of the neck of the ring or little
      metacarpal bone were randomized to receive three different types of treatment:
      dorso-ulnar plaster-of-Paris from the proximal interphalangeal joint to elbow;
      functional brace around the wrist; or elastic bandage. Twenty patients (19%) had
      to be excluded for different reasons leaving 85 patients in the study. The
      remaining patients were examined after 4 weeks and 3 months. There was no
      difference in patient satisfaction between the three different types of
      treatment. The functional brace was in our opinion superior to the two other
      types of treatment: the patients had as little pain as the patients treated with
      plaster-of-Paris and less pain than patients treated with elastic bandage.
      Patients treated with a functional brace mobilized as fast as patients treated
      with elastic bandage and faster than patients treated with plaster-of-Paris.
      Based on these findings, we recommend the functional brace for treatment of
      fractures of the neck of the ring and little metacarpals.

PMID- 9607672
TI  - The "S" Quattro Turbo in the management of neglected dorsal interphalangeal
      dislocations.
AB  - We have used the "S" Quattro Turbo to treat four neglected dorsal interphalangeal
      joint dislocations. At an average follow up period of 45 months, there was a mean
      increase in the range of movement of the PIP joints by 74 degrees and of the IP
      joint of the thumb or DIP joints by 45 degrees. We recommend this technique for
      treating dorsal dislocations of the interphalangeal joints of more than 3 weeks
      duration.

PMID- 9607673
TI  - Irreducible dislocation of the proximal interphalangeal joint of a finger.
AB  - We report a patient with an irreducible dislocation of the proximal
      interphalangeal joint which was due to entrapment of the head of the proximal
      phalanx in the opening of the flexor digitorum superficialis tendon just proximal
      to its chiasma.

PMID- 9607674
TI  - Acute transient bilateral trigger fingers.
AB  - A 30-year-old man presented with bilateral, simultaneous, transient triggering of
      the middle digits which developed acutely after prolonged and sustained use of a
      garden rotavator. He was asymptomatic in the period before presentation and has
      remained so 7 years since.

PMID- 9607675
TI  - Spontaneous recovery of trigger thumbs in children.
AB  - Forty-two children with trigger thumb were reviewed to determine the possibility
      of spontaneous recovery and the outcome of treatment. There were 22 boys and 20
      girls. All of them had a normal physical examination at birth. Ten patients had
      spontaneous recovery within 3 months of their initial visit. Thirty-two patients
      underwent surgical release. All of them had satisfactory results. Our findings
      suggest that spontaneous recovery of trigger thumb in children is possible and
      may be related to a traumatic cause for the condition. Delaying operation until
      after the age of 3 years will not affect the outcome.

PMID- 9607676
TI  - Early results of a modified Brunelli procedure for scapholunate instability.
AB  - Twenty-two patients with a diagnosis of scapholunate instability underwent a
      modified Brunelli procedure. The overall results of this short follow-up study
      showed that a majority of patients (17 out of 22) had relief of pain. Grip
      strength recovered well. Postoperative range of motion was reduced in extension
      and flexion, remained unchanged for radial deviation and improved for ulnar
      deviation. The radiological appearance of dynamic or static scapholunate
      instability did not change after the procedure. Most patients (17 out of 22) felt
      subjective improvement and would have the operation again. A significantly poorer
      result was seen in those patients with an unresolved medicolegal claim. Although
      short-term results are encouraging for some patients, the authors feel that more
      long-term follow-up is needed before recommending the procedure.

PMID- 9607677
TI  - Stabilization of an acute perilunate dislocation using the "TAG" suture anchor.
AB  - A case of acute perilunate dislocation associated with acute scapholunate
      dissociation and acute carpal tunnel syndrome is described in which the treatment
      was facilitated by the use of the TAG suture anchor.

PMID- 9607678
TI  - Palmar perilunate fracture-dislocation of the carpus.
AB  - We report an uncommon palmar translunate, transhamate carpal fracture
      dislocation. CT-scans with three-dimensional reconstruction were most helpful for
      the assessment of the injury, which was treated operatively through a palmar
      approach. The lunate and hamate fractures were fixed using mini-screws and the
      radial styloid fracture and the scaphoid were reduced and stabilized with K
      wires.

PMID- 9607679
TI  - Proximal and palmar dislocation of the lunate and proximal scaphoid as a unit in
      a case of scaphocapitate syndrome. A 32-month follow-up.
AB  - Various patterns of transscaphoid, transcapitate fracture-dislocations have been
      described in the literature. There is little information on the method of
      management and the long-term results of such severe and rare injuries. The case
      described here involved a transscaphoid, transcapitate, palmar perilunate
      fracture-dislocation with ejection of the proximal pole of the scaphoid and
      lunate into the palmar aspect of the forearm. The functional result 32 months
      after delayed open reduction and internal fixation is reported.

PMID- 9607680
TI  - Dislocation of the pisiform in a 9-year-old child.
AB  - A dislocated pisiform associated with type II Salter-Harris fractures of the
      distal radius and ulna in a 9-year-old child is described. Closed reduction
      followed by immobilization achieved good radiological and clinical results. The
      current literature on dislocation of the pisiform is reviewed.

PMID- 9607681
TI  - Suture anchor repair of chronic radial ligament injuries of the
      metacarpophalangeal joint of the thumb.
AB  - Five cases of chronic instability of the radial collateral ligament of the thumb
      metacarpophalangeal joint are presented. All patients were treated using the
      Mitek suture anchor to reattach the avulsed ligament to bone in its anatomical
      position. Tendon advancement or graft reinforcement was not used in conjunction
      with the repair. A stable thumb metacarpophalangeal joint was achieved in each
      case with no recurrent instability or pain found within 9 months of follow-up.
      Postoperatively, each patient exhibited a full return to activities of daily
      living within 2 to 3.5 months. Grip and pinch strength and range of motion were
      nearly the same as in the uninjured hand. We recommend the Mitek suture anchor as
      a simple and effective method of repairing the chronic radial collateral ligament
      injury. The importance of correct anatomical placement of the anchor is stressed,
      and guidelines for this are discussed.

PMID- 9607682
TI  - Recurrent metacarpal giant cell tumour treated by en bloc resection and
      metatarsal transfer.
AB  - Recurrent giant-cell tumours of bone have a higher risk of malignancy than
      primary giant-cell tumours of bone, and giant-cell tumours of bone in the hand
      are more likely to recur than those that arise elsewhere. Therefore, en bloc
      resection and reconstruction, or amputation, have been the accepted treatments
      for recurrent giant-cell tumours of bone in the hand. We describe two cases of
      successful transplantation of a metatarsal to a metacarpal, which was the site of
      a recurrent giant-cell tumour. The patients had satisfactory results 3 years
      later without problems in the foot. En bloc resection of the tumour and
      reconstruction with an autograft should be considered in the treatment of
      recurrent giant cell tumour of the hand.

PMID- 9607683
TI  - Giant-cell lesion in a sesamoid bone of the thumb.
AB  - We treated a 72-year-old woman by excision of the right thumb sesamoid which
      contained a giant-cell lesion. Nine years later she had normal function and no
      evidence of other lesions, recurrence or metastasis. We recommend that the
      diagnosis of giant-cell reparative granuloma and giant-cell tumour be considered
      when a bony mass in a sesamoid bone is discovered. Surgical excision at least in
      our one case was definitive treatment.

PMID- 9607684
TI  - Apocrine hidrocystoma of the finger.
AB  - An apocrine hidrocystoma occurring on the finger of a 55-year-old man is
      reported. The lesion presented as a solitary, painless cystic nodule on the
      dorsal aspect of the middle phalanx of the index finger. Apocrine hidrocystoma is
      a benign tumour developed from apocrine sweat glands, but the location of the
      lesion was, however, not consistent with reported locations of apocrine glands in
      the adult.

PMID- 9607685
TI  - An unusual Salter type 2 fracture of the distal phalanx.
AB  - An unusual Salter type 2 fracture of the distal phalanx is described. The
      metaphyseal fragment of the fracture consisted of a long and thin plate of bone
      corresponding to the insertion site of the flexor digitorum profundus tendon.
      Differences between this combined fracture and the isolated mallet deformity or
      flexor profundus tendon avulsion fracture are discussed.

PMID- 9607686
TI  - A positive parental history of high blood pressure.

PMID- 9607687
TI  - Microalbuminuria and cardiovascular risk: a word of caution.

PMID- 9607688
TI  - Relationship of parental history of high blood pressure to blood pressure:
      combined findings of three Japanese population samples, the INTERSALT study.
AB  - The relationship of parental history of high blood pressure (HBP) to blood
      pressure (BP) was estimated in three Japanese population samples, totalling 591
      men and women aged 20-59 years, from the INTERSALT study. Parental history of HBP
      was defined as reported HBP by their father and/or mother. With adjustment for
      antihypertensive medication, body mass index, alcohol intake, and Na/K ratio in
      24-h urine, for participants with a parental history of HBP compared to those
      without a history, BP was higher for three to four age-sex strata, both for
      systolic and diastolic pressure (SBP, DBP), by 3.3 to 6.8 and 2.7 to 5.5 mm Hg
      respectively, with four of these six positive associations statistically
      significant. This finding was stronger for persons aged 40-59 than for those aged
      20-39. These data support the judgment that for persons with a parental history
      of HBP, BP is apt to increase more with age due to combined effects of genetic
      and environmental factors. Such people especially need to control their
      lifestyles carefully, including to maintain an optimal intake of salt (eg, <70
      mmol/day) and a high potassium intake, to avoid high alcohol consumption, and
      keep weight moderate, for the prevention of hypertension.

PMID- 9607689
TI  - Microalbuminuria, renal function and waist:hip ratio in black hypertensive
      Jamaicans.
AB  - OBJECTIVE: To investigate the relationship between blood pressure (BP), renal
      haemodynamics, anthropometric measures of obesity and urinary albumin excretion
      in hypertension and in a control group. METHODS: Urinary albumin, BP and
      anthropometric measurements were carried out in patients attending the
      hypertension clinic of the University Hospital of the West Indies. A randomised
      stratified sample was then selected for renal haemodynamic assessment. A
      normoalbuminuric control group without hypertension or diabetes was also
      selected. Renal haemodynamics was assessed by measuring glomerular filtration
      rate using 51-chromium edetic acid (51Cr-EDTA) and renal blood flow using 125
      iodohippurate (125-PAH). RESULTS: Urinary albumin excretion was positively and
      significantly correlated with systolic pressure (beta = 0.011, P < 0.003, R =
      0.22), current body weight (beta = 0.014, P < 0.04, R = 0.15) and the presence of
      diabetes (beta = 0.9, P < 0.001, R = 0.3). In the sample selected for renal
      haemodynamics, patients with microalbuminuria had lower age-adjusted corrected
      renal blood flow (P < 0.006), effective renal plasma flow (P < 0.006) and higher
      filtration fraction (P < 0.006) when compared with patients without
      microalbuminuria. Glomerular filtration rate in patients with microalbuminuria
      was not different from those without. Urinary albumin excretion was positively
      and significantly correlated with systolic pressure (beta = 0.016, P < 0.003, R =
      0.40) and inversely related to corrected renal blood flow (beta = -1.13, P <
      0.0002, R = 0.46). Waist:hip ratio was inversely related to corrected renal blood
      flow (beta = -1.74, P < 0.02, adjusted R = 0.48). CONCLUSION: Systolic BP,
      diabetes and body weight were significant predictors of albuminuria in our
      patients. Microalbuminuria and body fat distribution as assessed by waist:hip
      ratio were important determinants of renal haemodynamics in this population.

PMID- 9607690
TI  - Can heart rate predict blood pressure response to anti-hypertensive drug therapy?
AB  - The use of heart rate in clinical practice is limited by its variability under
      measurement situations. The mean heart rate on ambulatory monitoring provides a
      more robust statistic for clinical use. We examined the relationship between mean
      heart rate on initial referral ambulatory blood pressure monitoring (ABPM) to the
      BP-lowering efficacy of the four main groups of anti-hypertensive medications, in
      a referral hypertensive population. Patients were retrospectively identified by
      review of the BP database, and data collected from the initial referral BP
      monitor off medication, and the subsequent ABPM after treatment with either beta
      blockers, diuretics, calcium antagonists or angiotensin-converting enzyme (ACE)
      inhibitors. The change in mean arterial BP from the initial to the subsequent
      ABPM (ie, as a result of treatment) was correlated with the mean heart rate on
      the initial ABPM. A moderate association was found for initial daytime heart rate
      and BP response to beta-blockers (r = 0.24, P = 0.02), and ACE inhibitors (r =
      0.14, P = 0.05). No such association was found for calcium antagonists or
      diuretics. When the groups were divided into those with a mean daytime heart rate
      <75 and > or =75 beats per min, BP reduction from beta-blocker and ACE inhibitor
      therapy was significantly greater in those patients with a higher daytime heart
      rate. We conclude that average daytime heart rate on pre-treatment ABPM can be
      useful as a predictor of BP response to beta-blockade or ACE inhibition.

PMID- 9607691
TI  - Effects of oral contraceptives containing different progestogens on sodium
      lithium countertransport in normal females.
AB  - In view of the lack of unanimity on the effect of long-term intake of combined
      oral contraceptives (OC) on external sodium-dependent lithium efflux, otherwise
      known as sodium-lithium countertransport (SLC), we undertook a double-blind study
      to investigate the possible interaction between SLC and OC in healthy women with
      regular menstrual cycles. In a group of 17 volunteers, aged 27.0 +/- 1.1 years
      (mean +/- s.e.m.) and weighing 61.4 +/- 2.0 kg, ingestion of 30 microg
      ethinyloestradiol + 150 microg desogestrel for 3 months caused an increase in SLC
      activity from a baseline value of 0.254 +/- 0.017 mmol/lcell x h to 0.274 +/-
      0.017 mmol/lcell x h (P = 0.05). The activity of the transport system after 6
      months treatment remained higher than at baseline (0.280 +/- 0.016 mmol/lcell x
      h, P < 0.025) but was comparable to that at 3 months. Blood pressure and weight
      remained unaltered during the study period. In a comparable group of 16
      volunteers of age 26.1 +/- 1.3 years and weight 63.5 +/- 2.1 kg, control SLC
      activity (0.218 +/- 0.012 mmol/lcell x h) was comparable to that after 3 months
      (0.215 +/- 0.011 mmol/lcell x h) and 6 months (0.216 +/- 0.011 mmol/lcell x h)
      intake of 35 microg ethinyloestradiol + 2 mg cyproterone acetate. Body weight and
      blood pressure remained similarly unchanged. These results not only confirm that
      long-term intake of OC may cause increased SLC activity, but also suggest that
      the type of the progesterone in the medication used could be an important
      determinant of such interaction.

PMID- 9607692
TI  - Physicians' opinions about the management of hypertension: changes in Finland
      between 1985 and 1992.
AB  - The successful management of hypertension requires an active involvement of
      physicians. We studied trends in Finnish physicians' opinions about the
      management of hypertension between 1985 and 1992. The response rates in these two
      random samples of physicians were 68% and 56%, respectively. Physicians who
      reported regularly treating hypertensive patients were included in our analyses
      (n1 = 319, n2 = 470). Fifty per cent of physicians used diastolic blood pressure
      of 100 mm Hg as a criterion for starting drug treatment and a goal blood pressure
      of 90 mm Hg was reported by 60% of physicians. Both levels decreased from 1985 to
      1992. The variation in both of these blood pressure levels as reported by the
      physicians were wide both in 1985 and 1992. The activity in promoting non
      pharmacological measures such as exercise and restriction of fat intake improved
      during this time period. The choice of drugs for anti-hypertensive therapy
      changed drastically from 1985 to 1992. For younger patients ACE inhibitors became
      the drug of choice and for older patients Ca-blockers gained popularity from
      diuretics. A similar shift can also be seen in the sales statistics. Whether this
      increased activity in starting drug therapy and using new drugs will improve the
      outcome of treatment remains to be seen.

PMID- 9607693
TI  - How accurate are sphygmomanometers?
AB  - The objective of this study was to assess the accuracy and reliability of mercury
      and aneroid sphygmomanometers. Measurement of accuracy of calibration and
      evaluation of physical conditions were carried out in 524 sphygmomanometers, 351
      from a hospital setting, and 173 from private medical offices. Mercury
      sphygmomanometers were considered inaccurate if the meniscus was not '0' at rest.
      Aneroid sphygmomanometers were tested against a properly calibrated mercury
      manometer, and were considered calibrated when the error was < or =3 mm Hg. Both
      types of sphygmomanometers were evaluated for conditions of cuff/bladder, bulb,
      pump and valve. Of the mercury sphygmomanometers tested 21 % were found to be
      inaccurate. Of this group, unreliability was noted due to: excessive bouncing
      (14%), illegibility of the gauge (7%), blockage of the filter (6%), and lack of
      mercury in the reservoir (3%). Bladder damage was noted in 10% of the hospital
      devices and in 6% of private medical practices. Rubber aging occurred in 34% and
      25%, leaks/holes in 19% and 18%, and leaks in the pump bulb in 16% and 30% of
      hospital devices and private practice devices, respectively. Of the aneroid
      sphygmomanometers tested, 44% in the hospital setting and 61% in private medical
      practices were found to be inaccurate. Of these, the magnitude of inaccuracy was
      4-6 mm Hg in 32%, 7-12 mm Hg in 19% and > 13 mm Hg in 7%. In summary, most of the
      mercury and aneroid sphygmomanometers showed inaccuracy (21% vs 58%) and
      unreliability (64% vs 70%).

PMID- 9607694
TI  - Audit of ambulatory blood pressure monitoring in the diagnosis and management of
      hypertension in practice.
AB  - This study was carried out to ascertain the value of ambulatory blood pressure
      monitoring (ABPM) in the diagnosis and treatment of hypertension in routine
      clinical practice. ABPM was performed during the daytime hours in 410 patients
      believed to be hypertensive after at least three measurements by their physician
      and one measurement by a nurse in a hypertension clinic. The diagnosis was
      confirmed in 70% of patients when 90 mm Hg diastolic blood pressure (BP) was used
      as the upper limit of normal, and 86.3% when 85 mm Hg was used. In 204 patients
      who were reviewed 5 years later there were 108 on medical treatment. This reduced
      diastolic pressure from a mean of 100.6 +/- 8.8 to 85.7 +/- 8.8 mm Hg. However,
      in 30% of patients the diastolic pressure was still above 90 mm Hg. In the 49
      patients with isolated clinic hypertension (ICH), who had remained untreated,
      diastolic pressure increased from 84.0 +/- 4.8 to 88.1 +/- 8.4 mm Hg over the 5
      years. In 19 of these the level exceeded 90 mm Hg. ABPM therefore improves
      diagnostic accuracy and prevents treatment of patients with ICH. This condition,
      however, requires follow-up since BP tends to rise with time in some patients.
      The audit also identified patients who had had a suboptimal response to medical
      treatment.

PMID- 9607696
TI  - Insulin sensitivity, sodium-lithium countertransport and platelet free calcium
      concentrations in normotensive men with a family history of hypertension.
AB  - Peripheral glucose disposal (assessed with the euglycaemic-hyperinsulinaemic
      clamp technique), Na+-Li+ countertransport in erythrocytes and the cytosolic free
      Ca2+ concentration in platelets were determined in 36 men from families with
      essential hypertension in at least two close relatives and in 28 age- and weight
      matched men from families without hypertension. All had diastolic blood pressure
      consistently below 90 mm Hg and a normal oral glucose tolerance test. The mean
      age of the study population as a whole was 37 years (range 24-46). Insulin
      sensitivity index values (glucose disposal/serum insulin concentration during the
      clamp) were lower in the familial hypertension group than in the control group,
      but the two groups did not differ in Na+-Li+-countertransport, or in the platelet
      cytosolic free Ca2+ concentration which was correlated to the waist: hip
      circumference ratio in both groups (r = 0.38 and r = 0.49, respectively). The
      present findings do not support the hypothesis that an increase in Na+-Li+
      countertransport activity or the platelet cytosolic free Ca2+ concentration is a
      marker of insulin resistance in hypertension prone men.

PMID- 9607695
TI  - Effects of age and gender on ambulatory blood pressure and heart rate.
AB  - In a large group of young (n = 194) and elderly (n = 148) healthy subjects, we
      explored the relationship between ambulatory blood pressure (BP) levels, within
      subject BP variability, and age in men and women. The questions asked were: Do
      elderly subjects display higher BP levels and variability compared to a young
      group? Are there gender differences in BP level and variability? Are these gender
      differences similar in the young and the elderly subjects? Do age or gender
      influence BP in a similar way during waking and during sleep? Subjects wore an
      ambulatory BP monitor (Accutracker II) for 24 h. Individual levels and
      variability (standard deviations) were calculated for periods when subjects were
      awake and during sleep. Systolic BP was higher in the elderly women than in the
      young group. In comparison to the young subjects, both elderly men and women had
      higher diastolic BP. BP variability while subjects were awake was higher in the
      elderly, in women in particular. The higher levels of BP variability found in the
      elderly women may indicate relatively higher risk for end-organ damage, such as
      silent cerebrovascular damage.

PMID- 9607697
TI  - Hypertension, hyperinsulinaemia and obesity in middle-aged Finns with impaired
      glucose tolerance.
AB  - The aim of the study was to analyse the data obtained from a 2-year follow-up
      study of middle-aged Finnish subjects (n = 183) with a previous history of
      impaired glucose tolerance (IGT) in order to elucidate the longitudinal
      relationships between hypertension, fasting hyperinsulinaemia and obesity.
      Hypertension was defined as either a systolic blood pressure (BP) of > or =160 mm
      Hg or a diastolic BP of > or =95 mm Hg or being on anti-hypertensive medication
      regardless of the BP value. Multiple logistic regression analysis adjusted for
      glucose tolerance status, serum lipids, exercise behaviour and alcohol
      consumption shows that the odds ratios of one unit (mU/l) increase in the
      baseline fasting insulin concentration were 1.13 (95% confidence interval 1.00
      1.28) for the 2-year incidence of hypertension in subjects with IGT at baseline.
      Baseline body mass index (BMI) also predicted the 2-year incidence of
      hypertension, with an odds ratio of 1.20 (95% CI 1.02-1.42). BMI correlated
      positively with fasting insulin level (r = 0.54, P < 0.001). It is concluded that
      an elevated fasting insulin concentration as well as an increased BMI preceded
      the onset of hypertension in subjects with IGT. It may suggest a causal
      relationship between hypertension and hyperinsulinaemia.

PMID- 9607698
TI  - Interaction between paired-pulse facilitation and long-term potentiation of
      minimal excitatory postsynaptic potentials in rat hippocampal slices: a patch
      clamp study.
AB  - Long-term potentiation is an experimental paradigm used to study synaptic
      plasticity and memory mechanisms. One similarity between long-term potentiation
      and memory is the existence of several distinct phases. However, our preliminary
      quantal analysis did not reveal essential differences in expression mechanisms of
      the early (< 1 h) and later (up to 3 h) phases of long-term potentiation. The
      data were compatible with presynaptic mechanisms of both phases. Another approach
      to distinguish between presynaptic and postsynaptic mechanisms is analysis of
      interaction between long-term potentiation and presynaptic paired-pulse
      facilitation. Such analysis had been previously done mainly with recordings of
      field potentials reflecting the activity of large neuronal populations. Only the
      early potentiation phase had been previously analysed with recordings from single
      neurons. The results from different groups were contradictory. In the present
      study, minimal excitatory postsynaptic potentials were recorded from CA1
      pyramidal neurons of rat hippocampal slices. Paired-pulse facilitation ratios
      were calculated for various periods (up to 2-3 h) following induction of long
      term potentiation. The ratio persistently decreased in the majority of neurons
      following long-term potentiation induction. The decrease in the paired-pulse
      facilitation ratio correlated with the magnitude of long-term potentiation and
      with the initial (pretetanic) facilitation ratio. Therefore, the general results
      of the present analysis was similar with the results of the quantal analysis: it
      is consistent with a strong involvement of presynaptic mechanisms in maintenance
      of both early and late phases of long-term potentiation. However, individual
      neurons could show variable changes in the paired-pulse facilitation, e.g.,
      increases at late (> 0.5-1 h) periods after tetanus. Calculations of partial
      correlations and regression analysis indicated that positive correlation between
      potentiation magnitude and initial (pretetanic) paired-pulse facilitation tended
      to increase in the late potentiation phase (1.5-2.5 h post-tetanus) indicating
      that different mechanisms are involved in the early (0.5 h post-tetanus) and the
      late phase of long-term potentiation. The findings are compatible with
      involvement of presynaptic mechanisms in both the early and late phases of long
      term potentiation. However, the results suggest that contribution of changes in
      release probability and in effective number of transmitter release sites may
      differ during the two phases. It is suggested that activation of silent synapses
      and increases in the number of transmission zones due to pre- and postsynaptic
      structural rearrangements represent important mechanisms of the late phase of
      long-term potentiation.

PMID- 9607699
TI  - Long-term cellular dysfunction after focal cerebral ischemia: in vitro analyses.
AB  - The long-term (< or = six months) functional consequences of permanent middle
      cerebral artery occlusion were studied with in vitro extra- and intracellular
      recording techniques in adult mouse neocortical slices. After survival times of
      one to three days, 28 days and six months, intracellular recordings from layers
      II/III pyramidal cells in the vicinity of the infarct did not reveal any
      statistically significant changes in the intrinsic membrane properties when
      compared to age-matched control animals. However, a pronounced hyperexcitability
      could be observed upon orthodromic synaptic stimulation in neocortical slices
      obtained from mice 28 days after induction of ischemia. Low-intensity electrical
      stimulation of the afferents elicited particularly in this group epileptiform
      extracellular field potential responses and intracellular excitatory postsynaptic
      potentials, that were longer in duration as compared to the controls. When the N
      methyl-D-aspartate receptor-mediated excitatory postsynaptic potential was
      pharmacologically isolated in a bathing solution containing 0.1 mM Mg2+ and 10
      microM 6-cyano-7-nitroquinoxaline-2,3-dione, the synaptic responses were longer
      and larger in the ischemic cortex as compared to the controls. Higher stimulus
      intensities evoked in normal medium a biphasic inhibitory postsynaptic potential,
      that contained in the 28 days post-ischemia group a prominent amino
      phosphonovaleric acid-sensitive component, indicating a strong concurrent
      activation of a N-methyl-D-aspartate receptor-mediated excitatory postsynaptic
      potential. This pronounced co-activation could only be observed in the 28 days
      ischemic group, and neither after one to three days or six months post-ischemia
      nor in the controls. The quantitative analysis of the efficiency of stimulus-
      evoked inhibitory postsynaptic potentials recorded in amino-phosphono-valeric
      acid revealed a reduction of GABA-mediated inhibition in ischemic cortex.
      Although this reduction in intracortical inhibition may already contribute to an
      augmentation of N-methyl-D-aspartate receptor-mediated excitation, our results do
      also indicate that the function of N-methyl-D-aspartate receptors is transiently
      enhanced in the ischemic cortex. This transient hyperexcitability does not only
      cause cellular dysfunction in the vicinity of the infarct, but may also
      contribute to neuronal damage due to excitotoxicity.

PMID- 9607700
TI  - Long-term changes of ionotropic glutamate and GABA receptors after unilateral
      permanent focal cerebral ischemia in the mouse brain.
AB  - Long-term hyperexcitability was found after unilateral, permanent middle cerebral
      artery occlusion in exofocal neocortical areas of the adult mouse [Mittmann et
      al. (1998) Neuroscience 85, 15-27]. The aim of the present study was to test the
      hypothesis in an identical paradigm of ischemia. whether alterations in the
      densities of both excitatory and inhibitory amino acid receptors may underlie
      these pathophysiological changes. Alterations in densities of [3H]dizocilpine,
      [3H]D,L-amino-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, [3H]kainate and
      [3H]muscimol binding sites were demonstrated with quantitative in vitro receptor
      autoradiography. All binding sites were severely reduced in the core of the
      ischemic lesion. A completely different reaction was found in the exofocal,
      histologically inconspicuous parts of the somatosensory cortex and the more
      remote neocortical areas of both hemispheres. The [3H]muscimol binding sites were
      significantly reduced four weeks after ischemia in the motor cortex, hindlimb
      representation area and exofocal parts of the primary and secondary somatosensory
      cortices of both hemispheres. The focus of the reduction in [3H]muscimol binding
      sites was found in lower layer V and upper layer VI. Contrastingly, the densities
      of [3H]dizocilpine binding sites were found to be increased in these areas,
      whereas those of [3H]D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
      and [3H]kainate binding sites did not show significant changes. The
      [3H]dizocilpine binding site density increased predominantly in layers III and
      IV. All binding sites were also reduced in the retrogradely reacting, gliotic
      part of the ipsilateral ventroposterior thalamic nucleus, whereas the [3H]D,L
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid binding sites were
      increased in the surround of the ipsilateral nucleus and no changes in binding
      sites were seen in the whole contralateral nucleus. We conclude that permanent
      local ischemia leads to a long-term and widespread impairment of the normal
      balance between binding sites of excitatory and inhibitory neurotransmitter
      receptors in neocortical areas far away from the focus of the post-ischemic
      tissue damage. The imbalance comprises an up-regulation of the [3H]dizocilpine
      binding sites in the ion channels of N-methyl-D-aspartate receptors and a down
      regulation of [3H]muscimol binding sites of the GABA(A) receptors in the ipsi-
      and contralateral neocortex. These changes at the receptor level explain the
      previously observed hyperexcitability with the appearance of epileptiform field
      potentials and the long duration of excitatory postsynaptic potentials four weeks
      after ischemia.

PMID- 9607701
TI  - Modular distribution of vasoactive intestinal polypeptide in the rat barrel
      cortex: changes induced by neonatal removal of vibrissae.
AB  - The distribution of vasoactive intestinal polypeptide-immunoreactive neuronal
      structures in the barrel cortex (posteromedial barrel subfield) of adult rats was
      analysed after unilateral removal of the vibrissal follicles of row C in neonatal
      rats. The hypothesis was tested whether the distribution of vasoactive intestinal
      polypeptide-immunoreactive structures depends on the normal anatomical
      organization of the specific sensory input. After three months survival the
      distribution of the vasoactive intestinal polypeptide-immunoreactive structures
      was morphometrically evaluated. This approach revealed alterations in the
      contralateral posteromedial barrel subfield, where the disappearance of barrel
      row C and a substantial increase in size mainly of barrel row D, but also of
      other rows could be detected. Increase in row D included both barrels and the
      interspace (septal segments between barrels in one row). As vasoactive intestinal
      polypeptide immunoreactivity of the barrel field was found previously to be
      localized in synaptic boutons involved in symmetric synapses, our present
      findings suggest that (i) the interspace is enriched in inhibitory vasoactive
      intestinal polypeptide-immunoreactive synapses as opposed to the excitatory
      thalamocortical input reaching the barrel hollow, (ii) the spatial distribution
      of the vasoactive intestinal polypeptide system in the barrel cortex is closely
      associated with the neuronal organization of the sensory input and reacts with a
      considerable plasticity to lesion-induced changes of the input, and (iii) the
      compensatory barrel hypertrophy in a row neighbouring the deafferented row
      involves an increasing number of vasoactive intestinal polypeptide-immunoreactive
      synapses per barrel.

PMID- 9607702
TI  - Spatial learning and physical activity contribute to the induction of fibroblast
      growth factor: neural substrates for increased cognition associated with
      exercise.
AB  - New evidence indicates that neural activity regulates the expression of trophic
      factors in the brain but regulation of these molecules by select aspects of
      behaviour remains solely a fascinating possibility. We report that following
      training in the Morris water maze, a spatial memory task, the hippocampus and
      cerebellum of learning rats exhibited an increase in basic fibroblast growth
      factor messenger RNA. Basic fibroblast growth factor messenger RNA levels were
      higher during the learning of the task and decreased once asymptotic performance
      was reached, suggesting an involvement of basic fibroblast growth factor in
      learning/memory. An active control group, which exercised for the same time as
      the learning group but the spatial learning component of the task was minimized,
      exhibited a minor increase in basic fibroblast growth factor messenger RNA. The
      intensification of the physical activity component of the task by massed or
      intensive training resulted in greater increases in basic fibroblast growth
      factor messenger RNA for both learning and yoked groups, but levels of basic
      fibroblast growth factor messenger RNA in the learning group remained higher than
      yoked only in the cerebellum. Changes in basic fibroblast growth factor were
      accompanied by an increase in astrocyte density in the hippocampus in agreement
      with described roles of basic fibroblast growth factor in astrocyte
      proliferation/reactivity. Results suggest that learning potentiates the effects
      of physical activity on trophic factor induction in select brain regions. Trophic
      factor involvement in behaviour may provide a molecular basis for the enhanced
      cognitive function associated with active lifestyles, and guide development of
      strategies to improve rehabilitation and successful ageing.

PMID- 9607703
TI  - Intracerebral fetal raphe implants normalize hippocampal function but not
      cerebrovascular control in serotonin-depleted adult rat brain.
AB  - The effects of hypercapnia upon local cerebral blood flow and local cerebral
      glucose utilization were measured by quantitative autoradiography in parallel
      groups of rats (six per group) which 14-16 weeks previously had been treated with
      the serotonergic neurotoxin, methylenedioxymethamphetamine, followed by
      implantation of fetal raphe or basal forebrain tissues. Following the
      experiments, transplants were visualized by acetylcholinesterase histochemistry,
      and serotonergic reinnervation assessed using [3H]paroxetine binding to serotonin
      reuptake sites. In methylenedioxymethamphetamine-treated rats, contralateral to
      the implants, [3H]paroxetine binding was reduced by between 50 and 90% in the
      neocortex and hippocampus. Hippocampal glucose utilization was significantly
      increased in these rats, and the normal increase in flow which accompanies
      hypercapnia was also significantly enhanced. High levels of [3H]paroxetine
      binding were found within the raphe transplants (308 +/- 13 fmol/mg tissue). In
      host brain adjacent to the implant, binding levels were normalized, and in these
      same areas glucose utilization was also normalized. Basal forebrain implants had
      no effect upon either [3H]paroxetine binding or glucose utilization. Raphe
      transplants did not, however, alter the enhanced cerebrovascular response to
      hypercapnia induced by methylenedioxymethamphetamine, even in those areas where
      there was evidence of serotonergic reinnervation. The transplants also showed the
      same enhanced response. In conclusion, intracerebral fetal raphe implants
      normalize hippocampal function but not cerebrovascular control in serotonin
      depleted adult rat brain, and despite not sharing the serotonergic deficit, blood
      flow in the implants follows that of the dysfunctional host.

PMID- 9607704
TI  - Pharmacology of sensory stimulation-evoked increases in frontal cortical
      acetylcholine release.
AB  - Recent research has demonstrated that a variety of sensory stimuli can increase
      acetylcholine release in the frontal cortex of rats. The aim of the present
      experiments was to investigate the pharmacological regulation of sensory
      stimulation-induced increases in the activity of basal forebrain cholinergic
      neurons. To this end, the effects of agonists and antagonists at a variety of
      neurotransmitter receptors on basal and tactile stimulation-evoked increases in
      frontal cortical acetylcholine release were studied using in vivo brain
      microdialysis. Tactile stimulation, produced by gently stroking the rat's neck
      with a nylon brush for 20 min, significantly increased frontal cortical
      acetylcholine release by more than 100% above baseline. The noradrenergic alpha2
      agonist clonidine (0.1 or 0.2 mg/kg) and alpha1 antagonist prazosin (1 mg/kg)
      failed to affect basal cortical acetylcholine release; however, both compounds
      significantly reduced the increases evoked by sensory stimulation. In contrast,
      the alpha2 antagonist yohimbine (3 mg/kg) increased basal cortical acetylcholine
      release, thereby preventing meaningful investigation of its effects on tactile
      stimulation-evoked increases. The benzodiazepine agonist diazepam (5 mg/kg)
      reduced, and the GABA(A) receptor antagonist picrotoxin (2 mg/kg) increased basal
      cortical acetylcholine release; in addition, diazepam attenuated the increases in
      cortical acetylcholine release evoked by tactile stimulation. While dopaminergic
      D1 (SCH 23390, 0.15 mg/kg) and D2 (raclopride, 1 mg/kg) receptor antagonists did
      not by themselves significantly influence the increases evoked by tactile
      stimulation, their co-administration produced a significant reduction. The opioid
      receptor antagonist naltrexone (1.5 mg/kg) failed to affect either basal or
      tactile stimulation-evoked increases in acetylcholine overflow. Finally, the non
      competitive N-methyl-D-aspartate receptor antagonist, dizocilpine maleate (MK
      801; 0.025 and 0.05 mg/kg) increased basal cortical acetylcholine release. These
      results confirm that cortically projecting cholinergic neurons are activated by
      sensory stimuli, and indicate that the increases in cortical acetylcholine
      release produced by tactile stimulation are inhibited by stimulation of alpha2 or
      blockade of alpha1 noradrenergic receptors, and by enhanced GABAergic
      transmission. In addition, simultaneous blockade of dopamine D1 and D2 receptors
      appears necessary to achieve a significant reduction of sensory stimulation
      evoked acetylcholine release in the frontal cortex. The results are consistent
      with the hypothesis that cortical acetylcholine release is a component of the
      neurochemistry of arousal and/or attention and indicate that this is modulated by
      GABAergic, noradrenergic and dopaminergic systems. In contrast, endogenous opioid
      actions do not appear to be involved.

PMID- 9607705
TI  - Control of the calcium concentration involved in acetylcholine release and its
      facilitation: an additional role for synaptic vesicles?
AB  - 2,5-Diterbutyl-1,4-benzohydroquinone, a specific blocker of Ca2+-ATPase pumps,
      increased acetylcholine release from an identified synapse of Aplysia, as well as
      from Torpedo and mouse caudate nucleus synaptosomes. Because 2,5-diterbutyl-1,4
      benzohydroquinone does not change the presynaptic Ca2+ influx, the enhancement of
      acetylcholine release could be due to an accumulation of Ca2+ in the terminal.
      This possibility was further checked by studying the effects of 2,5-diterbutyl
      1,4-benzohydroquinone on twin pulse facilitation, classically attributed to
      residual Ca2+. While preventing the fast sequestration of Ca2+ by presynaptic
      organelles, 2,5-diterbutyl-1,4-benzohydroquinone magnified both twin pulse
      facilitation observed under low extracellular Ca2+ concentration and twin pulse
      dysfacilitation observed under high extracellular Ca2+ concentration. Thus, it is
      concluded that 2,5-diterbutyl-1,4-benzohydroquinone, by preventing Ca2+ buffering
      near transmitter release sites, modulates acetylcholine release. As 2,5
      diterbutyl-1,4-benzohydroquinone was also shown to decrease by 50% the uptake of
      45Ca2+ by isolated synaptic vesicles, we propose that synaptic vesicles can
      control the presynaptic Ca2+ concentration triggering the release of
      neurotransmitter.

PMID- 9607706
TI  - Behavioural, physiological and morphological analysis of a line of apolipoprotein
      E knockout mouse.
AB  - Using apolipoprotein E knockout mice derived from the Maeda source [Piedrahita J.
      A. et al. (1992) Proc. natn. Acad Sci. US.A. 89, 4471 4475], we have studied the
      influence of apolipoprotein E gene deletion on normal CNS function by
      neurological tests and water maze learning, hippocampal ultrastructure assessed
      by quantitative immunocytochemistry and electron microscopy, CNS plasticity, i.e.
      hippocampal long-term potentiation and amygdaloid kindling, and CNS repair, i.e.
      synaptic recovery in the hippocampus following deafferentation. In each study
      there was little difference between the apolipoprotein E knockout mice and wild
      type controls of similar age and genetic background. Apolipoprotein E knockout
      mice aged eight months demonstrated accurate spatial learning and normal
      neurological function. Synaptophysin and microtubule-associated protein 2
      immunohistochemistry and electron microscopic analysis of these animals revealed
      that the hippocampal synaptic and dendritic densities were similar between
      genotypes. The induction and maintenance of kindled seizures and hippocampal long
      term potentiation were indistinguishable between groups. Finally, unilateral
      entorhinal cortex lesions produced a marked loss of hippocampal synaptophysin
      immunoreactivity in both groups and a marked up-regulation of apolipoprotein E in
      the wild-type group. Both apolipoprotein E knockout and wild-type groups showed
      immunohistochemical evidence of reactive synaptogenesis, although the
      apolipoprotein E knockout group may have initially shown greater synaptic loss.
      It is suggested that either apolipoprotein E is of no importance in the
      maintenance of synaptic integrity and in processes of CNS plasticity and repair,
      or more likely, alternative (apolipo)proteins may compensate for the loss of
      apolipoprotein E in the knockout animals.

PMID- 9607707
TI  - Relationships between striatin-containing neurons and cortical or thalamic
      afferent fibres in the rat striatum. An ultrastructural study by dual labelling.
AB  - Striatin, a recently isolated rat brain calmodulin-binding protein belonging to
      the WD-repeat protein family, is thought to be part of a calcium signal
      transduction pathway presumably specific to excitatory synapses, at least in the
      striatum. This study was aimed to specify the cellular and subcellular
      localization of striatin, and to determine the possible synaptic relationships
      between the two main excitatory afferent pathways, arising from the cerebral
      cortex and the thalamus, and the striatin-containing elements, in the rat
      striatum. Anterograde tract-tracing by means of biotinylated dextran amine
      injection in the frontoparietal cerebral cortex or the parafascicular nucleus of
      the thalamus was combined with immunogold detection of striatin. Striatin
      immunoreactivity was confined to the neuronal somatodendritic compartment,
      including spines. Whereas 90-95% of the striatal neurons were striatin-positive,
      only about 50% of the sections of dendritic spines engaged in asymmetrical
      synaptic contacts exhibited striatin labelling. Among the sections of striatin
      immunopositive dendritic spines, the number of immunogold particles ranged from
      one to more than seven, indicating an heterogeneity of the spine labelling.
      Moreover, within each class of spines presenting at least two silver-gold
      particles, the distribution of the particles varied from a clear-cut alignment
      under the postsynaptic densities (24-33% of spines) to a location distant from
      the synaptic area. In the cell bodies and dendrites, striatin labelling was
      usually not associated with the cytoplasmic membrane nor with the postsynaptic
      densities. In the striatum ipsilateral to the tracer injections, only 34.8% of
      the synaptic contacts formed by corticostriatal afferents involved striatin
      positive elements (slightly labelled dendritic spines), whereas 56.7% of the
      synaptic contacts formed by thalamostriatal boutons were made on striatin
      positive targets (mostly dendrites). In both cases, striatin labelling was
      usually not associated with the postsynaptic density. Most of the immunoreactive
      dendritic spines were in contact with unidentified afferents. These data reveal
      that striatin is expressed in the vast majority of the cell bodies of striatal
      spiny neurons, but is heterogeneously distributed among the dendritic spines of
      those neurons. Data also indicate a preferential relationship between striatin
      containing structures and afferents from the parafascicular thalamic nucleus with
      respect to the frontoparietal cerebral cortex. But, at the dendritic spine level,
      striatin may be involved in signal transduction mechanisms involving as yet
      unidentified excitatory afferents to striatal neurons.

PMID- 9607708
TI  - Immunohistochemical localization and quantification of glial fibrillary acidic
      protein and synaptosomal-associated protein (mol. wt 25000) in the ageing
      hippocampus following administration of 5,7-dihydroxytryptamine.
AB  - Responses to injury in the ageing hippocampus were assessed utilizing the
      synaptic markers glial fibrillary acidic protein and synaptosomal-associated
      protein (mol. wt 25,000) following administration of the neurotoxin, 5,7
      dihydroxytryptamine, into the fimbria-fornix and cingulum bundle to denervate
      serotonergic afferent input to the dorsal hippocampus. Age-dependent alterations
      in hippocampal immunohistochemical localization of glial fibrillary acidic
      protein and synaptosomal-associated protein were evaluated in female Fischer 344
      rats following serotonergic deafferentation with 5,7-dihydroxytryptamine. Across
      the lifespan, as indicated by measurements taken at three, 18, 21 and 29 months,
      marked increases in glial fibrillary acidic protein, but not synaptosomal
      associated protein immunoreactivity, occurred throughout the hippocampus at 21
      and 29 months compared to three and 18 months. Following three weeks pretreatment
      with 5,7-dihydroxytryptamine (20 microg total dose) or vehicle (0.1% ascorbic
      saline; 2 microl total volume) infused in the fimbria-fornix/cingulum bundle,
      immunohistochemical analysis demonstrated marked increases of glial fibrillary
      acidic protein, but not synaptosomal-associated protein, in the 18-month 5,7
      dihydroxytryptamine group compared to the 18-month vehicle and 3-month 5,7
      dihydroxytryptamine groups. Additionally, a significant increase in glial
      fibrillary acidic protein concentration was found by enzyme-linked immunosorbent
      assay in the 18-month 5,7-dihydroxytryptamine group compared to the 18-month
      vehicle and three-month 5,7-dihydroxytryptamine groups. These results demonstrate
      that selective neurotoxicant damage of the hippocampal serotonergic system
      differentially alters the expression of glial fibrillary acidic protein. This
      approach may provide a valuable tool to determine the ability of the hippocampus
      to respond to age-related neurodegenerative injury.

PMID- 9607709
TI  - Alterations in corticotropin-releasing hormone gene expression of central
      amygdaloid neurons following long-term paraventricular lesions and adrenalectomy.
AB  - Corticotropin-releasing hormone messenger RNA expression in the amygdala of rats
      after adrenalectomy and bilateral lesions of the hypothalamic paraventricular
      nucleus was examined by in situ hybridization histochemistry. Corticotropin
      releasing hormone messenger RNA-containing cells are abundant in the intermediate
      subdivision of the central amygdaloid nucleus. Some corticotropin-releasing
      hormone-labeled cells are scattered in other subdivisions of the central nucleus
      and throughout the anterior amygdaloid area. Five days after bilateral
      adrenalectomy, the number of corticotropin-releasing hormone messenger RNA
      containing cells was reduced both in the central nucleus and the anterior area of
      the amygdala. This reduction was prevented by corticosterone replacement and
      contrasts sharply with the known rise of corticotropin-releasing hormone
      messenger RNA in the paraventricular nucleus after adrenalectomy. Corticotropin
      releasing hormone messenger RNA expression in the amygdala was up-regulated in
      rats with six-week bilateral lesions of the paraventricular nucleus. This
      elevation in corticotropin-releasing hormone messenger RNA was not influenced by
      adrenalectomy or corticosterone, and it did not correlate with plasma levels of
      adrenocorticotrophic hormone or corticosterone. The possible direct innervation
      of the amygdala by the paraventricular nucleus is supported by the demonstration
      of labeled axons from the paraventricular nucleus to the amygdala after injection
      of an anterograde tracer, Phaseolus vulgaris leucoagglutinin, into the
      paraventricular nucleus. Labeled fibers take two courses: through the lateral
      hypothalamus ventral amygdalofugal path and through the stria terminalis. Data
      presented here suggest that the paraventricular nucleus-amygdala connection is
      likely to be inhibitory to corticotropin-releasing hormone neurons in the central
      amygdala. These neurons may participate in behavioral responses to stress
      effected through brainstem autonomic centers rather than directly through the
      hypothalamo-pituitary adrenal axis.

PMID- 9607710
TI  - GABAergic and cholinergic basal forebrain and preoptic-anterior hypothalamic
      projections to the mediodorsal nucleus of the thalamus in the cat.
AB  - The present study examined projections of GABAergic and cholinergic neurons from
      the basal forebrain and preoptic-anterior hypothalamus to the "intermediate" part
      of the mediodorsal nucleus of the thalamus. Retrograde transport from this region
      of the mediodorsal nucleus was investigated using horseradish peroxidase
      conjugated wheatgerm agglutinin in combination with peroxidase-antiperoxidase
      immunohistochemical staining for glutamic acid decarboxylase and choline
      acetyltransferase. A relatively large number of retrogradely-labelled glutamic
      acid decarboxylase-positive neurons are located in the basal forebrain, amounting
      to more than 7% of the total population of glutamic acid decarboxylase-positive
      cells in this region. Moreover, retrogradely-labelled choline acetyltransferase
      positive cells are interspersed among glutamic acid decarboxylase-positive
      neurons, accounting for about 6% of the total choline acetyltransferase-positive
      cell population in the basal forebrain. The glutamic acid decarboxylase-positive
      and choline acetyltransferase-positive retrogradely-labelled neurons are
      distributed throughout several regions of the basal forebrain, including the
      medial septum, the diagonal band of Broca, the magnocellular preoptic nucleus,
      the substantia innominata pars anterior, the substantia innominata pars
      posterior, and the globus pallidus where only a few retrogradely-labelled neurons
      were seen. The choline acetyltransferase-positive mediodorsal-projecting neurons
      are morphologically different from the choline acetyltransferase-positive neurons
      in the basal forebrain, suggesting that those projecting to the mediodorsal
      nucleus are a small proportion of the cholinergic neuronal population in the
      basal forebrain. In the preoptic-anterior hypothalamus, many retrogradely
      labelled glutamic acid decarboxylase-positive cells were found, amounting to more
      than 7% of the total population of glutamic acid decarboxylase-positive cells in
      this region. These retrogradely-labelled glutamic acid decarboxylase-positive
      neurons are distributed throughout the preoptic-anterior hypothalamus in a
      continuous line with those in the basal forebrain, including the lateral preoptic
      area, the medial preoptic area, the bed nucleus of the stria terminalis, and the
      anterior and dorsal hypothalamic areas. The highest percentage of mediodorsal
      projecting GABAergic neurons is in the anterior lateral hypothalamus where more
      than 25% of the total population of glutamic acid decarboxylase-positive cells
      project to the mediodorsal nucleus of the thalamus. Overall, of the large
      population of retrogradely-labelled neurons in the basal forebrain and preoptic
      anterior hypothalamus, a significant proportion are glutamic acid decarboxylase
      positive neurons (> 60% in the basal forebrain and > 30% in the preoptic-anterior
      hypothalamus), while the choline acetyltransferase-positive neurons amount to a
      smaller percentage of the neurons projecting to the mediodorsal nucleus (< 13% in
      the basal forebrain and < 2% in the preoptic-anterior hypothalamus). These
      results provide anatomical evidence of direct GABAergic projections from the
      basal forebrain and preoptic-anterior hypothalamic regions to the "intermediate"
      part of the mediodorsal nucleus in the cat. This GABAergic projection field could
      be the direct pathway by which the basal forebrain directly modulates thalamic
      excitability and may also be involved in mechanisms modulating
      electroencephalographic synchronization and sleep through the "intermediate"
      mediodorsal nucleus.

PMID- 9607711
TI  - Expression of 10 GABA(A) receptor subunit messenger RNAs in the motor-related
      thalamic nuclei and basal ganglia of Macaca mulatta studied with in situ
      hybridization histochemistry.
AB  - In situ hybridization histochemistry technique with [35S]UTP-labelled riboprobes
      was used to study the expression pattern of 10 GABA(A) receptor subunit messenger
      RNAs in the basal ganglia and motor thalamic nuclei of rhesus monkey. Human
      transcripts were used for the synthesis of alpha2, alpha4, beta2, beta3, gamma1
      and delta subunit messenger RNA probes. Rat complementary DNAs were used for
      generating alpha1, alpha3, beta1 and gamma2 subunit messenger RNA probes. Nigral,
      pallidal and cerebellar afferent territories in the ventral tier thalamic nuclei
      all expressed alpha1, alpha2, alpha3, alpha4, beta1, beta2, beta3, delta and
      gamma2 subunit messenger RNAs but at different levels. Each intralaminar nucleus
      displayed its own unique expression pattern. In the thalamus, gamma1 subunit
      messenger RNA was detected only in the parafascicular nucleus. Comparison of the
      expression patterns with the known organization of GABA(A) connections in
      thalamic nuclei suggests that (i) the composition of the receptor associated with
      reticulothalamic synapses, except for those in the intralaminar nuclei, may be
      alpha1alpha4beta2delta, (ii) receptors of various other subunit compositions may
      operate in the local GABAergic circuits, and (iii) the composition of receptors
      at nigro- and pallidothalamic synapses may differ, with those at nigrothalamic
      probably containing beta1 and gamma2 subunits. In the medial and lateral parts of
      the globus pallidus, the subthalamic nucleus and the substantia nigra pars
      reticularis, the alpha1, beta2 and gamma2 messenger RNAs were co-expressed at a
      high level suggesting that this subunit composition was associated with all
      GABAergic synapses in the direct and indirect striatal output pathways. Various
      other subunit messenger RNAs were also expressed but at a lower level. In the
      substantia nigra pars compacta the most highly expressed messenger RNAs were
      alpha3, alpha4 and beta3; all other subunit messenger RNAs studied, except for
      gamma1, alpha1 and alpha2, were expressed at a moderate to high level. In the
      striatum, the following subunit messenger RNAs were expressed (listed in order of
      decreasing signal intensity): alpha4, beta3, alpha2, alpha3, beta2, delta,
      gamma2, alpha1. The expression patterns found in the monkey were similar to those
      described in comparable nuclei in the rat by Wisden et al. [J. Neurosci. (1992),
      12, p. 1040]; however, the monkey nuclei displayed a much greater variety of
      GABA(A) receptor subunit messenger RNAs.

PMID- 9607712
TI  - Partial cloning and differential expression of ryanodine receptor/calcium-release
      channel genes in human tissues including the hippocampus and cerebellum.
AB  - Cellular Ca2+ signalling is an important factor in the control of neuronal
      metabolism and electrical activity. Although the roles of Ca2+-release channels
      are well established for skeletal and cardiac muscle, less is known about their
      expression and roles in the central nervous system, especially in the human
      brain. We have isolated partial complementary DNAs derived from the human
      ryanodine receptor Ca2+-release channel genes (ryr1, ryr2 and ryr3), and examined
      their expression in the human hippocampus and cerebellum. For comparison, we have
      included in our analysis an inositol trisphosphate Ca2+-release channel type I
      complementary RNA probe. All four messenger RNAs show widespread distribution in
      the human hippocampus, where ryr2 is the most abundant isoform, and all four are
      expressed in the human cerebellum. However, striking differences were seen
      between ryr and inositol trisphosphate Ca2+-release channel type I complementary
      RNA expression in the cerebellum, with inositol trisphosphate Ca2+-release
      channel type I messenger RNA being largely restricted to, and very highly
      expressed, in Purkinje cells, whereas ryr1, ryr2 and ryr3 were all expressed
      predominantly in the granular layer. The widespread expression of ryr isoforms in
      the human hippocampus and cerebellum suggests that ryanodine receptor proteins
      may have a central role in Ca2+ signalling and Ca2+ homeostasis in the human
      central nervous system. These may include roles in fundamental processes like
      synaptic plasticity. Furthermore, these Ca2+-release channels may be involved in
      pathogenic processes such as excitotoxicity, where excessive rises in
      intracellular Ca2+ concentration mediate neuronal cell death.

PMID- 9607713
TI  - The effects of adenine dinucleotides on epileptiform activity in the CA3 region
      of rat hippocampal slices.
AB  - Alpha, omega-adenine dinucleotides (Ap(n)A) consist of two adenosine molecules
      linked at the 5' position by phosphate groups, the number of which is denoted by
      n and can range from 2 to 6. The aim of this study was to investigate the effect
      of Ap4A and Ap5A on the rate of epileptiform activity. Hippocampal slices (450
      microm), when perfused with a medium containing no added magnesium and 4
      aminopyridine (50 microM), generate epileptiform activity of an interictal
      nature. Ap4A and Ap5A at 1 microM depressed the discharge rate to a significant
      extent. At this concentration adenosine (1 microM) did not produce any effect.
      However at 10 microM adenosine, Ap4A and Ap5A all decreased the burst frequency.
      Adenosine deaminase (0.2 U/ml) totally annulled the inhibition of epileptiform
      activity produced by 10 microM adenosine or 1 microM Ap4A and Ap5A. Adenosine
      deaminase did not significantly change the maximum depression of activity
      produced by 10 microM Ap4A and Ap5A. 8-cyclopentyl-1,3-dimethylxanthine, an A1,
      receptor antagonist, increased the basal rate of epileptiform activity and
      prevented the depression of burst discharges by Ap4A. 5'-adenylic acid deaminase
      converts AMP into IMP which is inactive. 5'-adenylic acid deaminase did not
      prevent the inhibitory effects of Ap4A. The results suggests that in the CA3
      region of the hippocampus, Ap4A and Ap5A act partly by stimulating xanthine
      sensitive receptors directly and partly through the formation of the metabolite,
      adenosine.

PMID- 9607714
TI  - Protection against kainate-induced excitotoxicity by adenosine A2A receptor
      agonists and antagonists.
AB  - The neuroprotective role of adenosine receptor agonists in various models of
      ischaemia and neuronal excitotoxicity has been attributed to adenosine A1
      receptor activation. In this study we examine the role of the A2A receptor in the
      kainate model of excitotoxicity. Kainate (10 mg/kg) was administered systemically
      10 min after the intraperitoneal injection of adenosine analogues. The A2A
      agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine
      hydrochloride (CGS21680) protected the hippocampus at concentrations of 0.1 and
      0.01 mg/kg, but not at 2 microg/kg. The addition of the centrally acting
      adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine partially
      reduced protection only in the CA3a region, suggesting that only a small
      proportion of the protection was attributable to the A1 receptor. A less potent
      A2A agonist, N6-[2-(3,5-dimethyoxyphenyl)-2-(2-methylphenyl)-ethyl]adenosine (1
      mg/kg), provided only partial protection against kainate. 4-(2-[7-Amino-2-[2
      furyl][1,2,4]triazolo[2,3-a][1,3,5]triazin-5-yl -amino]ethyl)phenol, a selective
      A2A antagonist, also showed protection against kainate-induced neuronal death,
      when administered alone or in combination with CGS21680. These results show that
      adenosine A2A receptor activation is protective against excitotoxicity. The
      protection is largely independent of A, receptor activation or blockade.

PMID- 9607715
TI  - Activation and inactivation properties of voltage-gated calcium currents in
      developing cat retinal ganglion cells.
AB  - The correlated activity of developing retinal ganglion cells is essential for the
      reorganization and refinement of retinogeniculate projections. Previous studies
      have uncovered marked changes in the spiking properties of retinal ganglion cells
      during this period of reorganization; however, a full understanding of the
      changes in the underlying ionic conductances has yet to be obtained. To this end,
      the whole-cell configuration of the patch-clamp technique was used to record
      currents conducted by voltage-gated calcium channels in 83 dissociated cat
      retinal ganglion cells obtained from animals aged between embryonic day 34 and
      postnatal day 105. Calcium currents, magnified by using barium as the major
      charge carrier, were isolated by substituting choline for Na+ in the bathing
      solution and Cs+ for K+ in the electrode solution. Three voltage-gated Ca2+
      conductances were identified based on their voltage dependence and kinetics of
      activation and inactivation: a transient low-voltage-activated conductance, a
      transient high-voltage-activated conductance and a sustained high-voltage
      activated conductance. During the developmental period examined there were
      significant increases in the densities of all three conductances, as well as
      significant changes in some of their activation and inactivation properties.
      These findings, together with those reported previously for the voltage-gated Na+
      and K+ conductances, are related to the generation of excitability in developing
      retinal ganglion cells during a period critical to the normal development of the
      visual system. Furthermore, while the sustained high-voltage-activated
      conductance was present in all of the retinal ganglion cells observed, only about
      72% expressed the transient high-voltage-activated current. During the
      developmental period examined, there was also an increase in the proportion of
      cells expressing the transient low-voltage-activated conductance. This, along
      with our previous finding that retinal ganglion cells heterogeneously express
      different types of voltage-gated K+ channels, strongly suggests that the spiking
      patterns observed in different classes of retinal ganglion cell may be due, in
      part, to their intrinsic membrane properties.

PMID- 9607716
TI  - Alterations in channel density and kinetic properties of the sodium current in
      retinal ganglion cells of the rat during in vivo differentiation.
AB  - Changes in the kinetic properties of voltage-activated sodium currents (I(Na))
      were studied in rat retinal ganglion cells during in vivo differentiation. Whole
      cell recordings from cells maintained as retinal slices or whole-mounts were
      examined using the patch-clamp technique in the perforated patch mode. Voltage
      clamp recordings revealed significant ontogenetic modifications in key properties
      of I(Na) and the present study described for the first time the detailed time
      course of such alterations. I(Na) was first expressed on embryonic day 17/18
      (E17/18). Current density increased during development from an average of -81
      pA/pF on E17/18 to a maximum of -747pA/pF on postnatal day 10/12 (P10/12).
      Simultaneously, the activation of I(Na) shifted towards more negative potentials,
      reflected by a shift in the potential of half-activation from -14.1 mV on E17/18
      to - 37.5 mV on P10/12. No significant changes in these parameters were observed
      after P10/12. Steady-state inactivation shifted first towards more positive
      potentials, reflected by a shift in the potential of half-inactivation from -51
      mV on E17/18 to -38 mV on P3/5, but shifted back towards more negative values
      thereafter (-44 mV in the adult). The most striking feature of I(Na) in rat RGCs
      was a transient slowing of I(Na) kinetics that was never described before. Time
      to peak and decay time constants increased between E20 and P5, resulting in slow
      and broad sodium currents within a developmental period that is characterized by
      intensive synaptogenesis in the target structures of retinal ganglion cells and
      maximum retinal ganglion cell death. Thereafter, time to peak and decay time
      constants decreased again to values found before E20, resulting in rapid sodium
      spikes. In conclusion, sodium currents in rat retinal ganglion cells displayed
      substantial electrophysiological changes during pre- and postnatal development.
      These changes in the sodium system had different temporal time patterns,
      indicating that they may play specific roles during the development of the visual
      system.

PMID- 9607717
TI  - Injection of corticotropin-releasing hormone into the locus coeruleus or foot
      shock increases neuronal Fos expression.
AB  - Previous research suggests that corticotropin-releasing hormone can act in the
      locus coeruleus to increase the firing of locus coeruleus neurons and elicit
      physiological responses resembling those associated with stress. The present
      study used immunocytochemical detection of Fos as a measure of neuronal
      activation to identify brain areas that were activated by bilateral injections of
      corticotropin-releasing hormone into the locus coeruleus of rats. Injection of
      corticotropin-releasing hormone into the locus coeruleus increased the expression
      of Fos in the locus coeruleus as compared with injection of vehicle into the
      locus coeruleus or injection of corticotropin-releasing hormone into neighbouring
      pontine sites. The pattern of Fos expression throughout the brain after
      injections of corticotropin-releasing hormone into the locus coeruleus was
      generally consistent with the anatomical organization of efferent projections
      arising from the locus coeruleus; increased Fos expression was observed in many
      brain areas including the ventral lateral septum, septohypothalamic nucleus, bed
      nucleus of the stria terminalis, the central amygdaloid nucleus, the dorsomedial
      nuclei of the hypothalamus, and the thalamic paraventricular and rhomboid nuclei.
      Foot shock also increased Fos expression in the locus coeruleus and the other
      brain regions that expressed Fos after corticotropin-releasing hormone injections
      into the locus coeruleus. A few brain regions, most notably the hypothalamic
      paraventricular nucleus, expressed Fos in response to foot shock but not
      corticotropin-releasing hormone. These results indicate that local injection of
      corticotropin-releasing hormone into the locus coeruleus stimulates the activity
      of the locus coeruleus neurons. However, the pattern of Fos expression throughout
      the brain evoked by injection of corticotropin-releasing hormone into the locus
      coeruleus does not fully replicate the effects of foot shock.

PMID- 9607718
TI  - Rejection of wild-type and genetically engineered major histocompatibility
      complex-deficient glial cell xenografts in the central nervous system results in
      bystander demyelination and Wallerian degeneration.
AB  - Mixed glial cell cultures prepared from neonatal wild type and mutant male mice
      lacking either major histocompatibility complex class I, class II or both class I
      and II molecules (major histocompatibility complex class I(o/o)II(o/o)), and from
      syngeneic male rats were transplanted into female rat spinal cord white matter.
      Graft survival was monitored using DNA probes specific to the Y chromosome.
      Survival of major histocompatibility complex class-deficient grafts was not
      prolonged compared to wild-type grafts and in most cases grafts could not be
      detected at 28 days post-transplantation, at which time syngeneic grafts were
      still present. However, rejection of xenografts resulted in significant bystander
      damage to host tissue. In recipients of wild-type and major histocompatibility
      complex class I(o/o) xenografts the predominant pathology was demyelination.
      Demyelination was also observed in recipients of major histocompatibility complex
      class II(o/o) and major histocompatibility complex class I(o/o)II(o/o)
      xenografts, however in addition there was marked collagen deposition and
      meningeal cell invasion. Significantly more axons had undergone Wallerian
      degeneration in recipients of major histocompatibility complex class II(o/o) and
      major histocompatibility complex class I(o/o)II(o/o) xenografts than recipients
      of wild-type and major histocompatibility complex class I(o/o) xenografts. These
      findings were interpreted as evidence of a more destructive immune response
      associated with rejection of grafts lacking major histocompatibility complex
      class II molecules. It was proposed that the difference in the severity of
      bystander damage may be related to the previously demonstrated ability of
      xenogeneic major histocompatibility complex class II molecules to activate host T
      cells directly, whereas xenografts lacking major histocompatibility complex class
      II molecules were capable of activating host T cells only by the indirect
      pathway.

PMID- 9607719
TI  - Effects of neurotoxins and hindpaw inflammation on opioid receptor
      immunoreactivities in dorsal root ganglia.
AB  - Three types of opioid receptors mediate peripheral opioid antinociception in
      inflammation. Recently, antisera that recognize unique epitopes of the cloned mu
      , delta-, and kappa-opioid receptors have been developed. Using these antisera we
      examined the regulation of opioid receptors in rat dorsal root ganglia after
      hindpaw inflammation and the influence of neurotoxins for primary afferent
      neurons and sympathetic neurons thereon. Peripheral tissue inflammation was
      produced by injection of complete Freund's adjuvant into the right hindpaw.
      Capsaicin was injected subcutaneously once a day for three days using a total
      dose of 150 mg/kg. 6-hydroxydopamine was injected intraperitoneally 75 mg/kg/day
      for three days. Freund's adjuvant induced a marked increase in the percentage of
      mu-, but a decrease in delta- and kappa-opioid receptor-positive neurons.
      Capsaicin significantly decreased mu-, delta- and kappa-opioid receptor
      immunoreactivity in both Freund's adjuvant treated and non-treated rats. No
      significant changes on the mu-, delta- and kappa-opioid receptor
      immunoreactivities were observed after 6-hydroxydopamine treatment in either
      Freund's adjuvant-treated or non-treated rats. Our studies indicate: (1)
      Peripheral inflammation can differentially regulate the expression of the three
      opioid receptors in dorsal root ganglia neurons with an up-regulation of mu- and
      down-regulation of delta- and kappa-opioid receptors. 2) A significant portion of
      mu-, delta- and kappa-opioid receptors are located on capsaicin-sensitive neurons
      in dorsal root ganglia of both non-inflamed and inflamed hindlimbs. 3) The
      expression of opioid receptors in dorsal root ganglia of either inflamed or non
      inflamed hindlimbs is not influenced by sympathetic postganglionic neurons.

PMID- 9607720
TI  - Differences in expression of oligosaccharides, neuropeptides, carbonic anhydrase
      and neurofilament in rat primary afferent neurons retrogradely labelled via skin,
      muscle or visceral nerves.
AB  - Dorsal root ganglion neurons innervating skin via the saphenous nerve, muscle via
      the gastrocnemius nerve and viscera via the splanchnic nerve, were identified by
      retrograde tracing with Fast Blue applied to the cut nerve. Only neuronal
      profiles with nuclei were counted. At the survival times used no changes in
      immunohistochemical labelling patterns were detectable in the axotomized neurons.
      Percentages of Fast Blue-labelled neuronal profiles that were immunolabelled were
      calculated. The values for markers of carbohydrate groups were for skin, muscle
      and viscera, respectively: the lectin peanut agglutinin 55%, 24%, and 50%; the
      lectin soybean agglutinin 72%, 56%, 61%; the antibody 2C5 (against lactoseries
      groups) 43%, 20%, 6%; the antibodies SSEA-4 (against globoseries groups) 6%, 12%,
      0% and SSEA-3 (against globoseries groups) 6%, 5%, 0%. The values for
      neurofilament rich profiles were for skin, muscle and viscera, respectively: 34%,
      43%, 19%, and for carbonic anhydrase were 10%, 33%, 2%. Values for neuropeptides
      were, for calcitonin gene-related peptide 51%, 70%, 99%, for substance P 21%,
      51%, 82%, and for somatostatin 10%, 2% and 0%. The population of skin afferents
      therefore contained the highest proportion of profiles expressing galactose
      containing carbohydrate groups labelled by 2C5 and the lectins and the highest
      proportion of cells with somatostatin. In contrast they had the lowest
      proportions of cells with calcitonin gene-related peptide and substance P,
      compared with the other tissues. Muscle afferents had the highest proportions
      compared with the other tissues of the neurofilament-rich, carbonic anhydrase
      positive and SSEA-4-labelled profiles, but the lowest proportions of profiles
      with lectin binding. The splanchnic visceral afferents had the highest
      proportions, compared with the other tissues, of neuronal profiles labelled for
      calcitonin gene-related peptide and substance P, but the lowest proportions of
      neurofilament rich profiles and of profiles with carbonic anhydrase or 2C5
      labelling and they totally lacked any labelling for globoseries carbohydrates and
      somatostatin. Both the muscle and skin afferent populations had clear small cell
      and large cell peaks in their size distributions, with the small cell peak being
      larger for skin than muscle afferents and the large cell peak being more marked
      for muscle afferents. The visceral afferent profiles had a unimodal size
      distribution with the peak size being between the small and large cell peaks of
      the somatic afferent units. This study therefore shows that the patterns of
      immunohistochemical labelling and cell size of primary afferent neurons differ
      according to their peripheral target tissue.

PMID- 9607721
TI  - Developmental regulation of myotonic dystrophy protein kinase in human muscle
      cells in vitro.
AB  - From our previous studies, myotonic dystrophy protein kinase: gene product of
      myotonic dystrophy is localized at the terminal cisternae of sarcoplasmic
      reticulum of human adult muscle. Now we have studied the developmental expression
      of myotonic dystrophy protein kinase in aneurally cultured human muscles and
      contracting cross-striated muscles innervated with fetal rat spinal cord using a
      semi-quantitative reverse transcription-polymerase chain reaction method for
      myotonic dystrophy protein kinase messenger RNA expression, Western blot
      analysis, immunohistochemical examinations by laser scanning confocal microscopy
      and immunoelectron microscopy. About 65,000 mol. wt myotonic dystrophy protein
      kinase was detected in aneurally cultured muscles. Myotonic dystrophy protein
      kinase messenger RNA was expressed in both aneurally and innervated cultured
      muscles, but in early innervated cultured muscles the message was transiently
      lower than in aneurally cultured muscles and innervated cultured muscles in long
      term co-culture. In aneurally cultured muscles, immature aneurally cultured
      muscles show a diffuse and irregular distribution of myotonic dystrophy protein
      kinase in the deeper cytoplasm near the nuclei. Ultrastructurally the immuno
      products against myotonic dystrophy protein kinase were observed as dense
      deposits in parts of the membranes near the mitochondria. In innervated cultured
      muscles, immunofluorescent microscopy showed myotonic dystrophy protein kinase to
      be localized regularly in the I bands and A-I junctions. Ultrastructurally
      myotonic dystrophy protein kinase was localized in branched duct-like membranes
      in the early stage of innervated cultured muscles and then in small sacs at the I
      bands and A-I junctions of the sarcolemma in the mature stage. Our present
      studies strongly suggest that innervation plays an important role in the
      localization of myotonic dystrophy protein kinase in human skeletal muscle during
      development. We conclude that the expression of myotonic dystrophy protein kinase
      during development is under neuronal influence.

PMID- 9607722
TI  - Steroid receptor isoforms: exception or rule?
AB  - Since the first steroid receptor was cloned, it was quickly identified as one of
      many such receptors constituting a gene superfamily which has grown to include
      not only steroid receptors but also receptors for thyroid hormone, retinoic acid,
      1,25-dihydroxyvitamin D3 as well as a number of less traditional ligands,
      including farnesoids and fatty acids. Interestingly, these receptors are far
      outnumbered by the 'orphan' receptors for which ligands are still being sought.
      The original cloning of nuclear receptors, although sometimes identifying more
      than one receptor form, led to the general premise that each ligand has its
      cognate receptor through which signal is transduced to the transcriptional
      machinery. Regulation of this process was found to occur at the level of receptor
      expression, ligand availability, and more recently, through post-translational
      modifications of the receptor and interaction of a variety of
      coactivators/corepressors with the receptor protein. The continuing
      identification of more than a single form for many of the receptors directed the
      attention of a number of investigators toward defining possible roles for these
      'extras'. This review examines the different forms of nuclear receptor gene
      family members and how they may provide an additional level of regulation.

PMID- 9607723
TI  - Mapping of the domain in the neuroendocrine protein 7B2 important for its helper
      function towards prohormone convertase PC2.
AB  - In the secretory pathway, the neuroendocrine polypeptide 7B2 transiently
      associates with its physiological target, the prohormone convertase PC2. The 7B2
      protein carries two functional domains involved in the control of proPC2
      maturation and activation, an inhibitory C-terminal region and an N-terminal
      domain displaying facilitative activity. Here, we show that a short segment in
      7B2 (His120-Pro131) is important for its facilitative activity. Site-directed
      mutagenesis indicates that within this segment. Tyr130 is particularly important
      for the ability of 7B2 to act as a helper protein for PC2.

PMID- 9607724
TI  - CYP21 pseudogene transcripts are much less abundant than those from the active
      gene in normal human adrenocortical cells under various conditions in culture.
AB  - The human steroid 21-hydroxylase pseudogene (CYP21P, also termed CYP21A) is
      transcribed in the adrenal cortex, but the relative abundance of transcripts from
      CYP21P and from the active CYP21 gene (also termed CYP21B) is not well
      established. In the present experiments we cultured primary human adrenocortical
      cells in defined medium and used RNase protection assays to examine whether there
      might be a selective increase in the relative abundance of CYP21P transcripts
      under any of the various regulatory factors known to affect expression of 21
      hydroxylase. Differences between the sequences of intron 2 in CYP21P and CYP21
      allowed the synthesis of gene-specific probes spanning exon 3 and parts of the
      adjacent introns. CYP21- and CYP21P-specific probes spanning the site of the
      start of transcription were also synthesized. CYP21 transcripts were readily
      detectable. In agreement with previous observations on 21-hydroxylase mRNA and
      enzyme activity in primary cultures of human adrenocortical cells, the abundance
      of CYP21 transcripts was increased by cyclic AMP analogues (N6-monobutyryl cyclic
      AMP and 8-bromo cyclic AMP), insulin, IGF-I and tetradecanoyl phorbol acetate
      (TPA). However, CYP21P transcripts were not detected in the presence of any of
      the various regulatory factors known to affect expression of 21-hydroxylase.

PMID- 9607725
TI  - Growth hormone receptor and regulation of gene expression in fetal lymphoid
      cells.
AB  - The role of growth hormone (GH) in modulating the adult immune response is
      receiving increased attention; however, its role in the development of immune
      competence in the fetus has not been defined. In order to begin to address the
      role of GH in the ontogeny of the immune response. cells from bovine fetal spleen
      and thymus were examined for GH receptor and responsiveness to GH. Northern
      analysis and ligand binding studies showed that growth hormone receptor (GHR) was
      readily detected in early- and mid-gestational fetal thymocytes, but it was less
      readily detected in thymocytes from older fetuses. In contrast, GHR was easily
      detected in splenocytes at all fetal ages. Thymocytes and splenocytes from mid
      gestational fetuses expressed low levels of cell surface GHR by flow
      cytofluorometric analysis, and CD4+ and CD8 (single positive) thymocyte subsets
      were positive. Northern analyses were employed to determine the effects of in
      vitro GH treatment on expression of several proto-oncogenes, cytokines, and GHR
      in thymocytes from fetuses at approximately mid-gestation. GH treatment for 30
      min down-regulated c-jun and c-fos mRNA approximately 2- and 2.8-fold,
      respectively. After 6 h treatment, GH increased transcript levels for interleukin
      (IL)-1alpha, IL-1beta, IL-6, and GM-CSF about 2.5-, 2.2-, 3-, and 2-fold,
      respectively. GH also down-regulated the expression of its own receptor about 3.2
      fold after 8 h of incubation. The presence of GHR in fetal lymphoid cells and its
      temporal and spatial regulation suggest a potential role for GH in the
      development and or function of the fetal bovine immune system. Although the
      mechanism(s) is unclear, our results suggest that GH is intimately involved in
      lymphocyte function and expression of certain cytokines during a critical period
      of fetal immune development.

PMID- 9607726
TI  - Interleukin-1 regulation of corticotropin-releasing factor (CRF), glucocorticoid
      receptor, c-fos and c-jun messenger RNA in the NPLC-KC cell line.
AB  - The NPLC-KC human hepatoma cell line expresses corticotropin-releasing factor
      (CRF) and it has been demonstrated that CRF secretion and synthesis in this cell
      line increases in response to activators of the protein kinase A (PKA) and C
      (PKC) pathways as well as interleukin-1 (IL1). CRF expression with all three
      agents can be inhibited with the synthetic steroid-dexamethasone (DEX). In this
      report, we have examined the effect of IL1 (beta form) in the presence and
      absence of DEX on CRF mRNA (mRNA) expression as well as the expression of human
      glucocorticoid receptor (GR) mRNA and the mRNA of the proto-oncogenes (c-jun and
      c-fos) that have been implicated in CRF regulation. NPLC-KC cells were incubated
      with picomolar concentrations of IL1. Following this total RNA was extracted from
      the cells and Northern Blots were probed with 32P-labelled human DNA probes for
      the CRF, GR, c-jun and c-fos genes. Levels of mRNA expression were measured using
      a PhosphoImager and were normalized to mRNA levels of control probe
      glyceraldehyde-3-phosphate dehydrogenase (GAPD). CRF mRNA was significantly
      increased with IL1 treatment in a time and concentration dependent manner. CRF
      mRNA expression increased with increasing concentrations of IL1 over the range of
      1-100 pM; expression of CRF mRNA also peaked after 24 h of 100 pM IL1 treatment
      and reached a level of expression approximately seven times higher than control.
      This pattern of expression was significantly inhibited in the presence of 100 nM
      DEX. Levels of the GR, c-fos and c-jun mRNAs were also significantly increased in
      the presence of IL1 and inhibited when DEX was co-incubated with IL1. The results
      reveal that IL1 stimulation of CRF mRNA expression by IL1 in the NPLC-KC cell
      line is accompanied by activation of GR mRNA as well as the mRNA of the immediate
      early genes--c-fos and c-jun. The results also demonstrate that this cell line
      may serve as a model system for the molecular mechanisms by which IL1 regulates
      CRF in central nervous system (CNS) neurons.

PMID- 9607727
TI  - Partial androgen insensitivity and correlations with the predicted three
      dimensional structure of the androgen receptor ligand-binding domain.
AB  - Genetic defects of the human androgen receptor (AR) can cause a wide spectrum of
      androgen insensitivity syndromes (AIS) ranging from phenotypic females in those
      with complete AIS; ambiguous genitalia in partial AIS; to male infertility in
      minimal AIS. The majority of these defects are due to point mutations resulting
      in amino acid substitutions. It is however unclear why certain mutations result
      in partial AIS, whereas others in the same exon cause the complete syndrome. We
      present a case of partial AIS due to a point mutation affecting codon 758 of the
      AR ligand-binding domain (LBD) that changed the sense of the codon from
      asparagine to threonine (N758T). The mutant receptor displayed normal binding
      affinity to DHT but abnormal dissociation kinetics in both patient's fibroblasts
      and transfected COS-7 cells. The mutant AR was thermolabile, and resulted in
      approximately 50% reduction in receptor transactivation capacity when examined
      with a reporter gene incorporating an androgen-response-element. Although the 3-D
      structure of AR LBD is not known, the homologous region in a member of the
      steroid receptor superfamily, retinoid-X receptor (RXR-alpha), has been
      crystallized, allowing comparison of aligned amino-acid sequences of RXR-alpha
      and AR. The mutation, N758T, lies in a predicted linker region between the fifth
      alpha-helix (H5) and the first beta-strand (S1). Generally, mutations leading to
      partial AIS tend to cluster in the predicted linker regions located between the
      structural helices of the AR LBD. Most strikingly, the predicted linker regions
      contain over 70% of the mutant ARs associated with prostate cancer in the LBD.
      The occurrence of mutations associated with both partial AIS and prostate cancer
      in the same predicted linker regions, suggest that this clustering is not
      coincidental and that the predicted linker regions are likely to have important,
      but subtle, roles in defining androgen binding and ligand specificity.

PMID- 9607728
TI  - Germline and somatic mutations of the RET proto-oncogene in apparently sporadic
      medullary thyroid carcinomas.
AB  - Medullary thyroid carcinomas (MTC) occur sporadically or as part of inherited
      multiple endocrine neoplasia (MEN) type 2 syndromes. To recognize misdiagnosed
      familial cases and to establish the frequency of somatic mutations, a series of
      50 patients, clinically diagnosed with sporadic MTC, were analyzed for mutations
      in the RET proto-oncogene. The clinical management of the patient and of the
      family is different in the two cases. Germline mutations were detected in three
      independent cases, demonstrating that they were associated to familial MTC. The
      mutations affected exon 11 in two cases and exon 14 in one case. Somatic
      mutations were detected in eight patients (30%) and they were indicative of
      sporadic MTC. In seven cases the mutation affected codon 918 of exon 16 and in
      one case codon 634 in exon 11. No RET mutations were detected in the remaining
      patients. A different genetic and clinical management is proposed for individuals
      with a diagnosis of familial or sporadic MTC.

PMID- 9607729
TI  - A role for NAD+ and cADP-ribose in melatonin signal transduction.
AB  - The hormone melatonin modulates constitutive protein secretion and inhibits cGMP
      in melanoma M2R cells via cholera-toxin (CTX) sensitive pathways. Activation by
      melatonin of CTX-substrates is due to enhancement of their ADP ribosylation. The
      possibility that ADP ribosylation was enhanced by elevation of NAD+ was studied.
      Melatonin enhanced NAD+ and decreased cADP-ribose in the cells, in a CTX
      independent pathway, indicating inhibition of nicotinamide adenine dinucleotide
      glycohydrolase (NADase). Dibutyryl cGMP (db-cGMP), which obviates the melatonin
      induced decrease in cGMP and prevents the modulation of protein secretion,
      abrogated the enhancement of NAD+. cADP-ribose is involved in calcium homeostasis
      and its decrease may reduce intracellular Ca2+. The intracellular Ca2+ chelator
      BAPTA/AM mimicked and Ca2+ ionophores prevented the melatonin-induced inhibition
      of protein secretion. These data indicate for the first time hormonal modulation
      of NADase resulting in two signals: (1) enhancement of NAD+ which may explain the
      increase in ADP ribosylation and activation of CTX substrates leading to
      facilitation of protein secretion; (2) suppression of cell cADP-ribose and
      consequently intracellular Ca2+ which may explain the melatonin-induced
      inhibition of protein secretion.

PMID- 9607730
TI  - Mouse insulin-like growth factor binding protein-6: expression, purification,
      characterization and histochemical localization.
AB  - The mitogenic and metabolic activities of insulin-like growth factors (IGF) are
      modulated by a family of six high affinity IGF binding proteins (IGFBPs). This
      study describes the expression of the mouse IGFBP-6 which is unique among IGFBPs
      in its preferential binding of IGF II, in insect cells using the baculovirus
      system. The purified, O-glycosylated IGFBP-6 was functional as shown by IGF
      binding and by inhibition of IGF II-stimulated DNA synthesis in human
      fibroblasts. Specific antibodies generated in chicken against the recombinant
      IGFBP-6 were used for Western blotting analysis and immunohistochemistry. Strong
      immunoreactivity was found in ossifying bones of the cranial base, in cell
      clusters of the pancreas anlage, in the trigeminal ganglion, on myoblasts, on
      motoneurons of the spinal cord of embryonic mice. In tissues of adult mouse,
      strong IGFBP-6 immunostaining was present in epidermal and peridermal layers of
      the skin, in meningeal layers, in long-striated skeletal muscle, and in the
      Langerhans' islets of the pancreas. No immunopositive staining was observed in
      lung and liver indicating that sites of synthesis and IGFBP action are different.

PMID- 9607731
TI  - Evolutionary divergence of the truncated growth hormone receptor isoform in its
      ability to generate a soluble growth hormone binding protein.
AB  - The soluble growth hormone binding protein (GHBP), which is encoded by the GH
      receptor (GHR) gene, is generated by several mechanisms. In rabbits (rb) and
      humans (h), it is derived by proteolytic cleavage of the full-length membrane
      bound receptor molecules (GHR-fl), whereas in rats (r) and mice, it results from
      an alternative splice excluding the transmembrane domain. Furthermore, in all
      these species, alternative splicing in the cytoplasmic domain results in a
      truncated isoform (GHR-tr), that, in humans, produces large amounts of GHBP
      through proteolysis. To further characterize the species specificity of the
      mechanism underlying GHBP generation, rbGHR-tr and rGHR-tr expressed in COS-7
      cells were assayed for their ability to produce a GHBP in comparison with the
      corresponding full-length receptors. Large amounts of GHBP were secreted by cells
      expressing the rabbit constructs, the rbGHR-tr isoform being more efficient in
      GHBP generation than rbGHR-fl. In contrast, no GHBP was detected from cells
      expressing rGHR-tr, the cytoplasmic deletion having no effect on GHBP release
      from membrane receptors. These data further demonstrate evolutionary divergence
      in the mechanism by which GHBP is generated and provide new clues to decipher the
      molecular process underlying the cleavage step.

PMID- 9607732
TI  - Estrogen receptor down-regulation is regulated noncooperatively by estrogen at
      the transcription level.
AB  - We examined noncooperativity of estrogen action by studying the transcription of
      estrogen receptor (ER) down-regulation in an ER stably transfected cell line
      (Rat1 + ER). The time-course of the ER transcription rate following 17beta
      estradiol (E2) (10 nM) treatment was measured by nuclear run-on assays. ER
      transcription rates decreased to 40 +/- 3% within 1 h as compared with no
      treatment and stayed suppressed to 24 h of E2 treatment. The ER transcription
      rate decrease was noncooperative when measured at 24 h of E2 treatment. This
      suggested that initial E2 binding to the ER is also a noncooperative process. The
      Hill coefficients of E2 binding to ER were near unity with an equilibrium
      dissociation constant of 1-3 nM when measured after a 1 h incubation. These
      results show that E2 noncooperatively binds ER and down-regulates transcription
      of ER noncooperatively in intact Ratl + ER cells.

PMID- 9607733
TI  - Invasive fungal infections in patients receiving intensive cytotoxic therapy for
      cancer.

PMID- 9607734
TI  - Empirical therapy of infections in neutropenic patients.

PMID- 9607735
TI  - The appropriate use of platelets: an update from the Edinburgh Consensus
      Conference.

PMID- 9607736
TI  - Treatment of haemophilia.

PMID- 9607737
TI  - Management of disseminated intravascular coagulation.

PMID- 9607738
TI  - Hyperhomocysteinemia is a risk factor for venous and arterial thrombosis.

PMID- 9607739
TI  - A challenge to genetic transparency.

PMID- 9607740
TI  - Clinton 'is failing to honour pledge on AIDS vaccine'.

PMID- 9607741
TI  - Europe's life patent moratorium may go...

PMID- 9607742
TI  - As US office claims right to rule on morality.

PMID- 9607743
TI  - Genome effort 'still in need of support'.

PMID- 9607745
TI  - UN reaches deal on biodiversity science.

PMID- 9607744
TI  - British funding boost is Wellcome news.

PMID- 9607746
TI  - Report released on INSERM laboratory.

PMID- 9607747
TI  - Nathanson takes top job at AIDS research office.

PMID- 9607748
TI  - Swiss democracy has its advantages.

PMID- 9607749
TI  - Swiss democracy has its advantages.

PMID- 9607750
TI  - Swiss democracy has its advantages.

PMID- 9607751
TI  - We aim to refresh science, not to rebel.

PMID- 9607752
TI  - BSE coordinator should have been full-time job.

PMID- 9607753
TI  - Sound grounds for computing dendrites.

PMID- 9607754
TI  - Molecular neuroendocrinology. Working backwards to find answers.

PMID- 9607755
TI  - Neurobiology. Knowing where you're going.

PMID- 9607756
TI  - Papillomavirus and p53.

PMID- 9607757
TI  - Hyde's horrors.

PMID- 9607758
TI  - Human gene for physical performance.

PMID- 9607759
TI  - Meteoritic oxide grain from supernova found.

PMID- 9607760
TI  - Role of a p53 polymorphism in the development of human papillomavirus-associated
      cancer.
AB  - The E6 oncoprotein derived from tumour-associated human papillomaviruses (HPVs)
      binds to and induces the degradation of the cellular tumour-suppressor protein
      p53. A common polymorphism that occurs in the p53 amino-acid sequence results in
      the presence of either a proline or an arginine at position 72. The effect of
      this polymorphism on the susceptibility of p53 to E6-mediated degradation has
      been investigated and the arginine form of p53 was found to be significantly more
      susceptible than the proline form. Moreover, allelic analysis of patients with
      HPV-associated tumours revealed a striking overrepresentation of homozygous
      arginine-72 p53 compared with the normal population, which indicated that
      individuals homozygous for arginine 72 are about seven times more susceptible to
      HPV-associated tumorigenesis than heterozygotes. The arginine-encoding allele
      therefore represents a significant risk factor in the development of HPV
      associated cancers.

PMID- 9607761
TI  - Herbicide resistance caused by spontaneous mutation of the cytoskeletal protein
      tubulin.
AB  - The dinitroaniline herbicides (such as trifluralin and oryzalin) have been
      developed for the selective control of weeds in arable crops. However, prolonged
      use of these chemicals has resulted in the selection of resistant biotypes of
      goosegrass, a major weed. These herbicides bind to the plant tubulin protein but
      not to mammalian tubulin. Here we show that the major alpha-tubulin gene of the
      resistant biotype has three base changes within the coding sequence. These base
      changes swap cytosine and thymine, most likely as the result of the spontaneous
      deamination of methylated cytosine. One of these base changes causes an amino
      acid change in the protein: normal threonine at position 239 is changed to
      isoleucine. This position is close to the site of interaction between tubulin
      dimers in the microtubule protofilament. We show that the mutated gene is the
      cause of the herbicide resistance by using it to transform maize and confer
      resistance to dinitroaniline herbicides. Our results provide a molecular
      explanation for the resistance of goosegrass to dinitroanaline herbicides, a
      phenomenon that has arisen, and been selected for, as a result of repeated
      exposure to this class of herbicide.

PMID- 9607762
TI  - An X-linked gene with a degenerate Y-linked homologue in a dioecious plant.
AB  - Most flowering plants are hermaphroditic, having flowers with both male and
      female parts. Less than 4% of plant species are dioecious (with individuals of
      separate sexes), and many of these species have chromosome-mediated sex
      determination. The taxonomic distribution of separate sexes and chromosomal sex
      determination systems in the flowering plants indicates that plant sex
      chromosomes have evolved recently through replicated, independent events,
      contrasting with the ancient origins of mammalian and insect sex chromosomes.
      Plant sex chromosomes, therefore, offer opportunities to study the most
      interesting early stages of the evolution of sex chromosomes. Here we show that a
      gene encoding a male-specific protein is linked to the X chromosome in the
      dioecious plant Silene latifolia, and that it has a degenerate homologue in the
      non-pairing region of the Y chromosome. The Y-linked locus has degenerated as a
      result of nucleotide deletion and the accumulation of repetitive sequences. We
      have identified both the first X-linked gene and the first pair of homologous sex
      linked loci to be found in plants. The homology between the active X-linked locus
      and the degenerate Y-linked locus supports a common ancestry for these two loci.

PMID- 9607763
TI  - Evidence for striatal dopamine release during a video game.
AB  - Dopaminergic neurotransmission may be involved in learning, reinforcement of
      behaviour, attention, and sensorimotor integration. Binding of the radioligand
      11C-labelled raclopride to dopamine D2 receptors is sensitive to levels of
      endogenous dopamine, which can be released by pharmacological challenge. Here we
      use 11C-labelled raclopride and positron emission tomography scans to provide
      evidence that endogenous dopamine is released in the human striatum during a goal
      directed motor task, namely a video game. Binding of raclopride to dopamine
      receptors in the striatum was significantly reduced during the video game
      compared with baseline levels of binding, consistent with increased release and
      binding of dopamine to its receptors. The reduction in binding of raclopride in
      the striatum positively correlated with the performance level during the task and
      was greatest in the ventral striatum. These results show, to our knowledge for
      the first time, behavioural conditions under which dopamine is released in
      humans, and illustrate the ability of positron emission tomography to detect
      neurotransmitter fluxes in vivo during manipulations of behaviour.

PMID- 9607764
TI  - The role of dendrites in auditory coincidence detection.
AB  - Coincidence-detector neurons in the auditory brainstem of mammals and birds use
      interaural time differences to localize sounds. Each neuron receives many narrow
      band inputs from both ears and compares the time of arrival of the inputs with an
      accuracy of 10-100 micros. Neurons that receive low-frequency auditory inputs (up
      to about 2 kHz) have bipolar dendrites, and each dendrite receives inputs from
      only one ear. Using a simple model that mimics the essence of the known
      electrophysiology and geometry of these cells, we show here that dendrites
      improve the coincidence-detection properties of the cells. The biophysical
      mechanism for this improvement is based on the nonlinear summation of excitatory
      inputs in each of the dendrites and the use of each dendrite as a current sink
      for inputs to the other dendrite. This is a rare case in which the contribution
      of dendrites to the known computation of a neuron may be understood. Our results
      show that, in these neurons, the cell morphology and the spatial distribution of
      the inputs enrich the computational power of these neurons beyond that expected
      from 'point neurons' (model neurons lacking dendrites).

PMID- 9607765
TI  - A prolactin-releasing peptide in the brain.
AB  - Hypothalamic peptide hormones regulate the secretion of most of the anterior
      pituitary hormones, that is, growth hormone, follicle-stimulating hormone,
      luteinizing hormone, thyroid-stimulating hormone and adrenocorticotropin. These
      peptides do not regulate the secretion of prolactin, at least in a specific
      manner, however. The peptides act through specific receptors, which are referred
      to as seven-transmembrane-domain receptors or G-protein-coupled receptors.
      Although prolactin is important in pregnancy and lactation in mammals, and is
      involved in the development of the mammary glands and the promotion of milk
      synthesis, a specific prolactin-releasing hormone has remained unknown. Here we
      identify a potent candidate for such a hormone. We first proposed that there may
      still be unknown peptide hormone factors that control pituitary function through
      seven-transmembrane-domain receptors. We isolated the complementary DNA encoding
      an 'orphan' receptor (that is, one for which the ligand is unknown). This
      receptor, hGR3, is specifically expressed in the human pituitary. We then
      searched for the hGR3 ligand in the hypothalamus and identified a new peptide,
      which shares no sequence similarity with known peptides and proteins, as an
      endogenous ligand. We show that this ligand is a potent prolactin-releasing
      factor for rat anterior pituitary cells; we have therefore named this peptide
      prolactin-releasing peptide.

PMID- 9607766
TI  - Elastin is an essential determinant of arterial morphogenesis.
AB  - Elastin, the main component of the extracellular matrix of arteries, was thought
      to have a purely structural role. Disruption of elastin was believed to lead to
      dissection of arteries, but we showed that mutations in one allele encoding
      elastin cause a human disease in which arteries are blocked, namely,
      supravalvular aortic stenosis. Here we define the role of elastin in arterial
      development and disease by generating mice that lack elastin. These mice die of
      an obstructive arterial disease, which results from subendothelial cell
      proliferation and reorganization of smooth muscle. These cellular changes are
      similar to those seen in atherosclerosis. However, lack of elastin is not
      associated with endothelial damage, thrombosis or inflammation, which occur in
      models of atherosclerosis. Haemodynamic stress is not associated with arterial
      obstruction in these mice either, as the disease still occurred in arteries that
      were isolated in organ culture and therefore not subject to haemodynamic stress.
      Disruption of elastin is enough to induce subendothelial proliferation of smooth
      muscle and may contribute to obstructive arterial disease. Thus, elastin has an
      unanticipated regulatory function during arterial development, controlling
      proliferation of smooth muscle and stabilizing arterial structure.

PMID- 9607767
TI  - Protein-primed RNA synthesis by purified poliovirus RNA polymerase.
AB  - A small protein, VPg, is covalently linked to the 5' end of the plus-stranded
      poliovirus genomic RNA. Poliovirus messenger RNA, identical in nucleotide
      sequence to genomic RNA, is not capped at its 5' end by the methylated structure
      that is common to most eukaryotic mRNAs. These discoveries presented two
      problems. First, as cap structures are usually required for translation of mRNA
      into protein, how does this uncapped viral RNA act as a template for translation?
      Second, what is the function of VPg? The identification of the internal ribosomal
      entry site, which allows the entry of ribosomes into viral mRNA independently of
      the 5' mRNA end, has solved the first conundrum. Here we describe the resolution
      of the second problem. VPg is linked to the genomic RNA through the 5'-terminal
      uridylic acid of the RNA. We show that VPg can be uridylylated by the poliovirus
      RNA polymerase 3Dpol. Uridylylated VPg can then prime the transcription of
      polyadenylate RNA by 3Dpol to produce VPg-linked poly(U). Initiation of
      transcription of the poliovirus genome from the polyadenylated 3' end therefore
      depends on VPg.

PMID- 9607768
TI  - Distinct roles of the co-activators p300 and CBP in retinoic-acid-induced F9-cell
      differentiation.
AB  - The related proteins p300 and CBP (cAMP-response-element-binding protein (CREB)
      binding protein)) are transcriptional co-activators that act with other factors
      to regulate gene expression and play roles in many cell-differentiation and
      signal transduction pathways. Both proteins have intrinsic histone
      acetyltransferase activity and may act directly on chromatin, of which histone is
      a component, to facilitate transcription. They are also involved in growth
      control pathways, as shown by their interaction with the tumour suppressor p53
      and the viral oncogenes E1A and SV40 T antigen. Here we report functional
      differences of p300 and CBP in vivo. We examined their roles during retinoic-acid
      induced differentiation, cell-cycle exit and programmed cell death (apoptosis) of
      embryonal carcinoma F9 cells, using hammerhead ribozymes capable of cleaving
      either p300 or CBP messenger RNAs. F9 cells expressing a p300-specific ribozyme
      became resistant to retinoic-acid-induced differentiation, whereas cells
      expressing a CBP-specific ribozyme were unaffected. Similarly, retinoic-acid
      induced transcriptional upregulation of the cell-cycle inhibitor p21Cip1 required
      normal levels of p300, but not CBP, whereas the reverse was true for p27Kip1. In
      contrast, both ribozymes blocked retinoic-acid-induced apoptosis, indicating that
      both co-activators are required for this process. Thus, despite their
      similarities, p300 and CBP have distinct functions during retinoic-acid-induced
      differentiation of F9 cells.

PMID- 9607769
TI  - Cytokines, estrogen, and postmenopausal osteoporosis--the second decade.

PMID- 9607770
TI  - Endotoxin injection increases growth hormone and somatostatin secretion in sheep.
AB  - Endotoxin has been shown to stimulate GH secretion in human and sheep. However,
      changes in hypothalamic neurohormones involved in the GH regulation by endotoxin
      have never been studied in vivo. In sheep it is possible to collect hypophysial
      portal blood (HPB) and quantify GH-releasing hormone (GHRH) and somatostatin
      (SRIH) secretion under physiological conditions. The purpose of this study was to
      determine the effect of an acute i.v. endotoxin administration on the secretion
      of these peptides in sheep. Endotoxin induced a sustained increase of GH (x6.2 +/
      1.3) in intact rams. This stimulation was delayed and less marked when compared
      with the hypothalamic-pituitary-adrenal axis. Surprisingly, the GH increase was
      associated with an important rise of jugular (x10.6 +/- 2.4) and portal (x7.9 +/-
      3) SRIH levels, without a significant GHRH increase. To determine if the portal
      SRIH increase was a consequence of an increased short feedback of GH, we studied
      GH response to endotoxin after a previous GHRH injection to deplete the pituitary
      pools of GH. In that case, despite the absence of increase of GH after endotoxin
      treatment, SRIH levels was markedly increased. For the first time we have
      observed an experimental situation in sheep with a simultaneous and closed
      amplitude increase in jugular and portal SRIH. The source of jugular SRIH is
      likely the gastrointestinal tract and the increased jugular SRIH release in
      systemic circulation might be in part responsible for the increase of hypophysial
      portal SRIH. Ultimately our results show that endotoxin induced a complex
      reaction at multiple levels with a specific increase in both portal and
      peripheral SRIH levels. The surprising association of a lack of change in GHRH
      release and an increased secretion of SRIH with the increase of GH suggests that
      the effect of endotoxin on GH axis is mainly a pituitary one. The selective
      blockade of somatostatin should be useful for a better knowledge of the role of
      SRIH stimulation in the physiopathology of septic shock.

PMID- 9607771
TI  - Glucose metabolism in Goto-Kakizaki rat islets.
AB  - Islets from Goto-Kakizaki (GK) rats from our colony, despite marked impairment of
      glucose-induced insulin release, used glucose and produced CO2 at a rate 3 times
      that of islets from control Wistar rats. Almost all glucose used was accounted
      for in CO2 and lactate production. The percentages of glucose carbon used
      collected in CO2 and lactate were similar for control and GK islets. GK islets
      also oxidized 40% more acetate and leucine to CO2 than did control islets. The
      fraction of carbon leaving the Krebs cycle relative to CO2 production was the
      same in GK and control islets. The capacities of mitochondria from GK islets to
      generate ATP from glutamate and malate were similar and that to generate ATP from
      succinate and rotenone was somewhat less from GK islets. The reason for the
      enhanced utilization of substrates by islets of the GK rat is not apparent. In
      conclusion, there is no decrease in islet glucose utilization, glucose oxidation,
      Krebs cycle function, or the electron transport system evident from these
      measurements to explain the impaired insulin release in islets from GK rats.

PMID- 9607772
TI  - Desensitization of the beta-adrenergic response in human brown adipocytes.
AB  - Activation of adenylyl cyclase by beta-adrenergic receptors (betaARs) plays a
      major role in adipose tissue homeostasis. The increase in cAMP promotes lipolysis
      in white adipose tissue, activates both thermogenesis and lipolysis in brown
      adipose tissue (BAT), and induces BAT hypertrophy. Previous studies indicated
      that among the three betaAR subtypes present in adipose tissue, beta3AR could be
      a potential target for antiobesity treatments in humans. We studied immortalized
      human brown adipocytes (PAZ6 adipocytes) as a model of beta-adrenergic response
      in human BAT. PAZ6 adipocytes and freshly isolated mature human brown adipocytes
      display the same proportions of betaAR subtypes, with beta3AR being the most
      abundant (approximately 80% of the total). However, beta3AR was poorly coupled to
      the adenylyl cyclase pathway in PAZ6 cells, contributing to only 10% of the
      isoproterenol-induced accumulation of cAMP, whereas 20% and 70% of the signal
      depended on beta1- and beta2-subtypes, respectively. Upon isoproterenol
      stimulation, beta1- and beta2AR down-regulated with a half-life of about 3 h and
      the beta3AR with a half-life of 30-40 h. Long term stimulation with both
      saturating (micromolar) and nonsaturating (nanomolar) concentrations of beta
      adrenergic agonists caused a complete desensitization of the beta-adrenergic
      response at the adenylyl cyclase level and loss of stimulated protein kinase A
      activity and CREB phosphorylation. These results suggest that cAMP-dependent
      processes will be desensitized upon permanent treatment with beta3AR agonists.
      Further studies should establish whether the beta3AR is coupled to other
      signaling pathways in human brown adipocytes and whether these may contribute to
      BAT hypertrophy and/or thermogenesis.

PMID- 9607773
TI  - The role of calcium in the transcriptional and posttranscriptional regulation of
      the gonadotropin-releasing hormone gene in GT1-7 cells.
AB  - The role of calcium in the regulation of GnRH gene expression and the mechanism
      for its effects were examined in the present study. Using the immortalized
      hypothalamic GT1-7 cell line, which synthesizes and secretes GnRH, we
      demonstrated by ribonuclease protection assay and Northern blot analysis that
      these cells respond to treatment with the calcium ionophores ionomycin and A23187
      with an inhibition of transcription of the GnRH gene and decreases in GnRH
      messenger RNA (mRNA) levels. Ionomycin treatment caused the GnRH mRNA half-life
      to decrease from 25 to 9 h, concomitant with a decrease in mRNA poly(A) tail
      length, suggesting that ionomycin causes a decrease in GnRH mRNA stability. The
      ionomycin inhibitory effect on GnRH cytoplasmic mRNA levels was significantly
      inhibited in the presence of cycloheximide or the RNA synthesis inhibitor 5,6
      dichloro-1beta-ribofuranosylbenzimidazole, indicating that novel protein/RNA
      synthesis is obligatory for this effect. We conclude that an increase in calcium
      levels caused by ionomycin inhibits GnRH gene expression at multiple levels,
      including GnRH gene transcription and mRNA stability in GT1-7 cells.

PMID- 9607774
TI  - Thyroid hormones regulate beta-amyloid gene splicing and protein secretion in
      neuroblastoma cells.
AB  - The beta-amyloid protein (Abeta), the major component of the senile plaques found
      in Alzheimer brains, derives from a larger beta-amyloid precursor protein (APP).
      Alternative splicing of the APP gene yields three major APP messenger RNAs
      (mRNAs), which, in turn, give rise to the APP770, APP751, and APP695 protein
      isoforms. In this study we examined the effects of thyroid hormone on APP
      expression in N2a-beta neuroblastoma cells. T3 caused a significant increase in
      the APP770 mRNA band, in detriment of the APP695 mRNA, which was proportionately
      reduced. In agreement with these results, T3 markedly altered the relative ratio
      of intracellular APP isoforms, increasing the amount of APP770 and causing an
      equivalent reduction of the immature APP695 isoform. In accordance with these
      results, the soluble APP695-derived form was specifically reduced in the culture
      medium obtained from T3-treated cells. In contrast, the increase in intracellular
      APP770 was not followed by an enhanced release of soluble derivatives of this
      isoform. These results suggest that T3 regulates not only APP gene splicing, but
      also the processing and secretion of the APP peptides. According to our results,
      thyroid hormone might play a role in the development of Alzheimer's disease by
      modulating the intracellular and extracellular contents of APP isoforms.

PMID- 9607775
TI  - Hormonal regulation of liver fatty acid-binding protein in vivo and in vitro:
      effects of growth hormone and insulin.
AB  - Liver fatty acid-binding protein (LFABP) is an abundant protein in hepatocytes
      that binds most of the long chain fatty acids present in the cytosol. It is
      suggested to be of importance for fatty acid uptake and utilization in the
      hepatocyte. In the present study, the effects of bovine GH (bGH) and other
      hormones on the expression of LFABP and its messenger RNA (mRNA) were studied in
      hypophysectomized rats and in vitro using primary cultures of rat hepatocytes.
      One injection of bGH increased LFABP mRNA levels about 5-fold after 6 h, but
      there was no effect of this treatment on LFABP levels. However, 7 days of bGH
      treatment increased both LFABP mRNA and LFABP protein levels 2- to 5-fold. Female
      rats had higher levels of LFABP than male rats. Hypophysectomy of female rats,
      but not that of male rats, decreased LFABP levels markedly. Treatment of
      hypophysectomized rats with bGH for 7 days as two daily injections or as a
      continuous infusion increased LFABP levels to a similar degree. This finding
      indicates that the sex difference in the expression of LFABP is not regulated by
      the sexually dimorphic secretory pattern of GH. Neither insulin nor insulin-like
      growth factor I treatment of hypophysectomized rats for 6-7 days had any effect
      on LFABP mRNA or LFABP levels. In vitro, bGH dose-dependently increased the
      expression of LFABP mRNA, but only in the presence of insulin. Insulin alone had
      a marked dose-dependent effect on LFABP mRNA levels and was of importance for
      maintaining the expression of LFABP mRNA during the culture. Incubation with bGH
      increased LFABP mRNA levels within 3 h. GH had no effect on LFABP mRNA levels in
      the presence of actinomycin D, indicating a transcriptional effect of GH.
      Incubation with glucagon in vitro decreased LFABP mRNA levels markedly,
      indicating that glucagon, in contrast to GH, has an effect opposite that of
      insulin on LFABP mRNA expression. It is concluded that GH is an important
      regulator of LFABP in vivo and in vitro. In contrast to the effect of GH on
      insulin-like growth factor I mRNA, the presence of insulin was a prerequisite for
      the effect of GH on LFABP mRNA expression in vitro. The results emphasize the
      role of GH in the regulation of hepatic fatty acid metabolism.

PMID- 9607776
TI  - Gonadotropin and gonadal steroid release in response to a gonadotropin-releasing
      hormone agonist in Gqalpha and G11alpha knockout mice.
AB  - In this study, we used mice lacking the G11alpha [G11 knockout (KO)] or Gqalpha
      gene (Gq KO) to examine LH release in response to a metabolically stable GnRH
      agonist (Buserelin). Mice homozygous for the absence of G11alpha and Gqalpha
      appear to breed normally. Treatment of (5 wk old) female KO mice with the GnRH
      agonist Buserelin (2 microg/100 microl, sc) resulted in a rapid increase of serum
      LH levels (reaching 328 +/- 58 pg/25 microl for G11 KO; 739 +/- 95 pg/25 microl
      for Gq KO) at 75 min. Similar treatment of the control strain, 129SvEvTacfBr for
      G11 KO or the heterozygous mice for Gq KO, resulted in an increase in serum LH
      levels (428 +/- 57 pg/25 microl for G11 KO; 884 +/- 31 pg/25 microl for Gq KO) at
      75 min. Both G11 KO and Gq KO male mice released LH in response to Buserelin (2
      microg/100 microl of vehicle; 363 +/- 53 pg/25 microl and 749 +/- 50 pg/25 microl
      1 h after treatment, respectively). These values were not significantly different
      from the control strain. In a long-term experiment, Buserelin was administered
      every 12 h, and LH release was assayed 1 h later. In female G11 KO mice and
      control strain, serum LH levels reached approximately 500 pg/25 microl within the
      first hour, then subsided to a steady level (approximately 100 pg/25 microl) for
      109 h. In male G11 KO mice and in control strain, elevated LH release lasted for
      13 h; however, LH levels in the G11 KO male mice did not reach control levels for
      approximately 49 h. In a similar experimental protocol, the Gq KO male mice
      released less LH (531 +/- 95 pg/25 microl) after 13 h from the start of treatment
      than the heterozygous male mice (865 +/- 57 pg/25 microl), but the female KO mice
      released more LH (634 +/- 56 pg/25 microl) after 1 h from the start of treatment
      than the heterozygous female mice (346 +/- 63 pg/25 microl). However, after the
      initial LH flare, the LH levels in the heterozygous mice never reached the basal
      levels achieved by the KO mice. G11 KO mice were less sensitive to low doses (5
      ng/per animal) of Buserelin than the respective control mice. Male G11 KO mice
      produced more testosterone than the control mice after 1 h of stimulation by 2
      microg of Buserelin, whereas there was no significant difference in Buserelin
      stimulated testosterone levels between Gq KO and heterozygous control mice. There
      was no significant difference in Buserelin stimulated estradiol production in the
      female Gq KO mice compared with control groups of mice. However, female G11 KO
      mice produced less estradiol in response to Buserelin (2 microg) compared with
      control strain. Although there were differences in the dynamics of LH release and
      steroid production in response to Buserelin treatment compared with control
      groups of mice, the lack of complete abolition of these processes, such as
      stimulated LH release, and steroid production, suggests that these G proteins are
      either not absolutely required or are able to functionally compensate for each
      other.

PMID- 9607777
TI  - Evidence for mineralocorticoid receptor facilitation of glucocorticoid receptor
      dependent regulation of hypothalamic-pituitary-adrenal axis activity.
AB  - These studies further evaluated the relative role of mineralocorticoid (type I)
      and glucocorticoid (type II) receptors in mediating corticosteroid feedback
      regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Acute treatment of
      rats with the selective mineralocorticoid receptor antagonist, RU28318 (50 mg/kg
      sc), produced elevated basal corticosterone levels in the morning, but had no
      effect on basal corticosterone levels in the evening or on restraint stress
      corticosterone levels at either time of day. Acute treatment with the selective
      glucocorticoid receptor antagonist, RU40555 (30 mg/kg sc) had no effect on basal
      or restraint stress corticosterone levels at either time of day. However,
      combined treatment with RU28318 and RU40555 produced an elevation of evening
      basal corticosterone levels (and morning basal on one occasion) and produced an
      increase in corticosterone levels during and after stress at both times of day.
      In a separate experiment conducted in the morning, the combined RU28318 and
      RU40555 treatment also produced elevated ACTH responses during restraint stress.
      Based on available corticosteroid receptor measures, the RU28318 treatment was
      estimated to selectively occupy approximately 85% of mineralocorticoid receptors
      in rat brain, whereas the RU40555 treatment was estimated to selectively occupy
      approximately 50% of glucocorticoid receptors in rat brain. We conclude that
      mineralocorticoid receptor activation is necessary and sufficient to maintain low
      basal corticosterone levels during the circadian trough, whereas glucocorticoid
      receptor activation is necessary to constrain corticosterone secretion during the
      circadian peak or during acute stress. However, even during the circadian peak or
      acute stress, mineralocorticoid receptor activation plays an important role in
      facilitating the glucocorticoid receptor dependent regulation of HPA axis
      activity by corticosterone.

PMID- 9607778
TI  - Stabilization of the receptor protein tyrosine phosphatase-like protein ICA512 in
      GH4C1 cells upon treatment with estradiol, insulin, and epidermal growth factor.
AB  - Treatment with 1 nM estradiol, 300 nM insulin, and 5 nM epidermal growth factor
      induces secretory granule accumulation and prolactin storage in GH4C1 rat
      pituitary tumor cells. The same triple treatment induced more than 6-fold
      accumulation of both the precursor (100 kDa, pro-ICA512) and the mature forms (60
      70 kDa, ICA512 transmembrane fragment) of ICA512, a receptor protein tyrosine
      phosphatase-like protein that is preferentially localized in secretory granule
      membranes. Accumulation of ICA512 resembles that of prolactin storage, for the
      combination of all three, estradiol, insulin, and epidermal growth factor, gave
      the greatest induction, which was maximal at 4 days. This effect was specific, as
      the levels of the small GTP-binding protein Rab3, which is also associated with
      secretory granule membranes, were unaffected by the triple hormone/growth factor
      treatment. Increased transcription and translation of ICA512 could only partially
      account for its 6-fold accumulation, as ICA512 messenger RNA and ICA512 synthesis
      levels were 1.8 +/- 0.35- and 1.6 +/- 0.17-fold in triple treated GH4C1 cells
      compared with those in untreated cells, respectively. Pulse-chase procedures
      showed that pro-ICA512 was more stable in treated cells. These results indicate
      that the enlargement of the secretory granule compartment results in the
      stabilization of ICA512 and raise the possibility that trafficking of secretory
      granules may affect ICA512's function and vice versa.

PMID- 9607779
TI  - Luteinizing hormone releasing hormone (LHRH) neurons maintained in nasal explants
      decrease LHRH messenger ribonucleic acid levels after activation of GABA(A)
      receptors.
AB  - Inhibition of the LHRH system appears to play an important role in preventing
      precocious activation of the hypothalamic-pituitary-gonadal axis. Evidence points
      to gamma-aminobutyric acid (GABA) as the major negative regulator of postnatal
      LHRH neuronal activity. Changes in LHRH messenger RNA (mRNA) levels after
      alterations of GABAergic activity have been reported in vivo. However, the extent
      to which GABA acts directly on LHRH neurons to effect LHRH mRNA levels has been
      difficult to ascertain. The present work evaluates the effect of GABAergic
      activity, via GABA(A) receptors, on LHRH neuropeptide gene expression in LHRH
      neurons maintained in olfactory explants generated from E11.5 mouse embryos.
      These explants maintain large numbers of primary LHRH neurons that migrate from
      bilateral olfactory pits in a directed manner. Using in situ hybridization
      histochemistry and single cell analysis, we report dramatic alterations in LHRH
      mRNA levels. Inhibition of spontaneous synaptic activity by GABA(A) antagonists,
      bicuculline (10(-5) M) or picrotoxin (10(-4) M), or of electrical activity by
      tetrodotoxin (TTX, 10(-6) M) significantly increased LHRH mRNA levels. In
      contrast, LHRH mRNA levels decreased in explants cultured with the GABA(A)
      receptor agonist, muscimol (10(-4) M), or KCl (50 mM). The observed responses
      suggest that LHRH neurons possess functional pathways linking GABA(A) receptors
      to repression of neuropeptide gene expression and indicate that gene expression
      in embryonic LHRH neurons, outside the CNS, is highly responsive to alterations
      in neuronal activity.

PMID- 9607781
TI  - Differential expression of peroxisome proliferator-activated receptor-alpha, 
      beta, and -gamma during rat embryonic development.
AB  - The expression patterns of the three different peroxisome proliferator-activated
      receptor (PPAR) isotypes have been determined during rat embryonic development by
      in situ hybridization. The expression of PPARalpha starts late in development,
      with increasing levels in organs such as liver, kidney, intestine, and pancreas,
      in which it will also be present later in adulthood to regulate its specific
      target genes. PPARalpha is also transiently expressed in the embryonic epidermis
      and central nervous system. PPARgamma presents a very restricted pattern of
      expression, being strongly expressed in brown adipose tissue, in which
      differentiation it has been shown to participate. Like PPARalpha, it is also
      expressed transiently in the central nervous system. Interestingly, PPARalpha, 
      beta and -gamma are coexpressed at high levels in brown adipose tissue. Finally,
      the high and ubiquitous expression of PPARbeta suggests some fundamental role(s)
      that this receptor might play throughout development.

PMID- 9607780
TI  - The xenoestrogen bisphenol A induces growth, differentiation, and c-fos gene
      expression in the female reproductive tract.
AB  - The xenoestrogen bisphenol A (BPA) has been shown to mimic estrogen both in vivo
      and in vitro. BPA stimulates PRL secretion and the expression of a PRL regulating
      factor from the posterior pituitary in the estrogen-sensitive Fischer 344 rat
      (F344), but not in Sprague-Dawley (SD) rats. The goal of the present studies was
      to examine the in vivo actions of BPA on the reproductive tract. The specific
      objectives were 1) to characterize the short term effects of BPA on cell
      proliferation and c-fos expression in the uterus and vagina, and 2) to compare
      the effects of prolonged exposure to low doses of BPA on the reproductive tract
      of F344 and SD rats. Treatment with single high doses of BPA induced cell
      proliferation in the uterus and vagina of ovariectomized F344 rats, as determined
      by bromodeoxyuridine immunostaining. This proliferation was dose dependent (from
      37.5-150 mg/kg) and followed a time course similar to that of estradiol (E2).
      Quantitative RT-PCR revealed that both BPA and E2 increased c-fos messenger RNA
      levels in the uterus 14- to 16-fold within 2 h, which returned to basal levels
      after 6 h. In the vagina, BPA-induced c-fos expression remained elevated for up
      to 6 h, compared with the transient increase caused by E2. Treatment of F344 rats
      for 3 days with continuous release capsules that supplied a much lower dose of
      BPA (approximately 0.3 mg/kg x day) resulted in hypertrophy, hyperplasia, and
      mucus secretion in the uterus and hyperplasia and cornification of the vaginal
      epithelium. The reproductive tract of SD rats did not respond to this treatment
      paradigm with BPA. These studies demonstrate that 1) the molecular and
      morphological alterations induced by BPA in the uterus and vagina are nearly
      identical to those induced by estradiol; 2) the vagina appears to be especially
      sensitive to the estrogenic actions of BPA; 3) the reproductive tract of the
      inbred F344 rat appears more sensitive to BPA than that of the outbred SD rat;
      and 4) continuous exposure to microgram levels of BPA is sufficient for exerting
      estrogenic actions.

PMID- 9607782
TI  - Ontogeny of oxytocin receptors and oxytocin-induced stimulation of prostaglandin
      synthesis in prepubertal heifers.
AB  - Developmental aspects of oxytocin (OT) receptors (OTR) in uterine tissues before
      puberty are not known. Bovine ovaries secrete some estradiol, but no
      progesterone, before puberty; the circulating levels of estradiol are between 1
      and 3 pg/ml until puberty. Cross-bred Angus-Brahman heifers, in which puberty
      occurs around 12 months of age, were used to determine the concentrations of OTR
      from the late fetal stage to adulthood. PGF2alpha release in response to OT was
      determined in 3-, 6-, and 9-month-old heifers (n = 4 each). Myometrium,
      endometrium, and cervical mucosa were obtained from 3-week-old, 3-month-old, 6
      month-old, and 9-month-old heifers and from adult cows at estrus. Whole uterus
      and cervix were taken from third trimester fetuses and at birth. [3H]OT binding
      and specificity, localization of immunoreactive (ir) OTR, OTR messenger RNA, and
      OT-induced release of PGF2alpha were determined. The uterus from fetuses and the
      neonate expressed OTR messenger RNA and bound [3H]OT. At 3 weeks of age, OTR
      concentrations per mg protein were very low, but at 3 months of age they had
      increased markedly in all three tissues. At 6 and 9 months of age, levels of OTR
      had risen further and were similar to those in adult cows at estrus. Prepubertal
      uterus also possessed separate vasopressin VP1 subtype receptors. The ir-OTR was
      localized in luminal epithelial cells of endometrium and cervical mucosa, most of
      which were ir positive, whereas in myometrium, clusters of ir-OTR-positive cells
      were found among large numbers of ir-OTR-negative cells. The PGF2alpha response
      to OT was insignificant in heifers of all age groups, in contrast to that in cows
      at estrus. Endometrial cells from 4- to 5-month-old heifers did not respond to OT
      with PG release in the absence or presence of added arachidonic acid. Tumor
      promoters, lipopolysaccharide, and interleukin-2 also failed to elicit PG release
      in vitro, although they induced PG release in similar cell cultures from cyclic
      cows. In summary, uterine tissues of prepubertal heifers have high levels of OTR,
      which appear to be developmentally regulated. These receptors are not coupled to
      PG synthase, or alternatively, the PG synthase gene is not expressed before
      puberty, possibly because the tissues have had no previous exposure to
      progesterone.

PMID- 9607783
TI  - Effects of sex steroids on secretory granule formation in gonadotropes of
      castrated male rats with respect to granin expression.
AB  - Pituitary gonadotropes show sex-related differences in their ultrastructure.
      Typical gonadotropes of male rats exhibit both large granules, which contain
      chromogranin A (CgA), and small granules, which contain secretogranin II (SgII).
      In contrast, typical female rat gonadotropes show only a very few large granules
      among the numerous small granules. To clarify the nature of the biogenesis of
      these secretory granules and the effects of sex steroids, the ultrastructural and
      immunocytochemical changes in gonadotropes were examined in castrated male rats
      supplied with a testosterone or estradiol implant. In castrated rats, pituitary
      expression and plasma levels of LH increased drastically, but the pituitary
      content of CgA decreased. The majority of gonadotropes then showed features of
      "castration cells" containing many small secretory granules. A testosterone
      implant to castrated rats remarkably suppressed the expression and circulating
      levels of LH and increased the CgA content in the pituitary to near-normal
      levels. In this situation, immunocytochemical studies demonstrated that
      gonadotropes again exhibited large and small secretory granules with the
      respective localization of CgA and SgII. On the contrary, in castrated rats
      supplied with an estradiol implant, the expression and content of CgA in the
      pituitary were remarkably suppressed, and large secretory granules disappeared
      from gonadotropes. These results suggest that the expression of CgA in
      gonadotropes is regulated differently by male and female sex steroids. These
      different effects of androgen and estrogen on the expression level of CgA are
      closely associated with the sex-related differences in the ultrastructure of
      secretory granules within gonadotropes.

PMID- 9607784
TI  - The pattern and tempo of the pubertal reaugmentation of open-loop pulsatile
      gonadotropin-releasing hormone release assessed indirectly in the male rhesus
      monkey (Macaca mulatta).
AB  - The purpose of this study was to determine the pattern and tempo of the open-loop
      reaugmentation of pulsatile GnRH release at the time of puberty in the male
      rhesus monkey. Episodic LH secretion from the in situ pituitary, in which
      responsiveness to GnRH was first heightened and subsequently sustained by priming
      with an i.v. intermittent infusion of the synthetic peptide, was used as an index
      of GnRH discharges. Ten male monkeys were castrated between 12 and 20 months of
      age, implanted with indwelling venous catheters, and housed in specialized cages
      that permitted remote access to the venous circulation with minimal restraint and
      without interfering with the light-dark cycle. Endogenous GnRH release was
      assessed by examining moment-to-moment changes in circulating LH concentrations
      measured at 12-min intervals for 7 h while GnRH priming was temporarily
      interrupted. A discharge of GnRH was inferred whenever a pulse of LH secretion
      was identified by a pulse detection program. Examination of nocturnal pulsatile
      GnRH release (1900-0200 h) was initiated as early as 14 months of age. GnRH
      release was assessed at 40-day intervals before 20 months of age and at 10-day
      intervals whenever possible thereafter. A simple algorithm was developed to
      identify the age at which a developmental increase in hypophysiotropic drive to
      the gonadotroph occurred. This was termed day zero and was considered to
      represent the age at which a pubertal mode of GnRH release was initiated. After
      the initiation of pubertal GnRH release was established, alternate nighttime and
      daytime (1100-1800 h) assessments of GnRH were performed. Before day zero, which
      was observed between 24 and 29 months of age, a stable, low frequency (<1 pulse/7
      h), low amplitude pattern of pulsatile GnRH release was observed. Termination of
      the prepubertal mode of GnRH pulse generator activity was manifest as a
      relatively rapid nocturnal shift to a robust high-frequency pattern of activity.
      In some animals, the nocturnal acceleration to an adult GnRH pulse frequency (6-7
      pulses/7 h) was attained within an epoch of only 30 days. Although initiation of
      the pubertal acceleration in nocturnal GnRH pulse generator activity seemed to be
      associated with an increase in GnRH pulse amplitude, it was not possible to
      decipher the subsequent developmental changes in this parameter. In some animals,
      the pattern of pulsatile GnRH release after the initiation of the pubertal
      acceleration was punctuated by periods of diminished activity, which seemed to be
      unrelated to the state of the pituitary-adrenal axis. These findings demonstrate
      that the neurobiological mechanisms that lead to the termination of the
      prepubertal mode of diminished GnRH release, and that therefore initiate the
      insidious process of puberty, have the potential to unfold with a surprisingly
      rapid time course. The extent to which the intrinsic tempo of the pubertal
      acceleration of pulsatile GnRH release in the agonadal situation is dampened by
      testicular feedback in the intact monkey remains to be established.

PMID- 9607785
TI  - Rat G protein-coupled receptor kinase GRK4: identification, functional
      expression, and differential tissue distribution of two splice variants.
AB  - G protein-coupled receptor kinases (GRKs) specifically phosphorylate the agonist
      occupied form of G protein-coupled receptors, leading to the homologous mode of
      desensitization. We report here on the cloning of complementary DNAs that encode
      two rat GRK4 variants. Rat GRK4A (575 amino acids) displays 76% identity with the
      long human GRK4 splice variant. Rat GRK4B (545 amino acids) delineates a new
      variant that is identical to GRK4A except for a 31-amino acid deletion in the N
      terminal domain, corresponding to exon VI in the human GRK4 gene. GRKs4A and B
      are likely produced by alternative splicing from a single gene, the partial
      characterization of which revealed a structural organization similar to that of
      the human GRK4 gene. GRK4A messenger RNA (mRNA) is abundant only in testis. A
      combination of in situ hybridization and quantitative RT-PCR studies demonstrated
      that GRK4A mRNA level increases during testicular development and predominates in
      leptotene to late pachytene primary spermatocytes and round spermatids. GRK4B
      mRNA is poorly expressed in testis and most rat tissues but is heterogeneously
      distributed in the kidney, with 20-fold enrichment in the outer medulla. GRKs4A
      and B are both functional protein kinases, as demonstrated in a rhodopsin
      phosphorylation assay. The differential tissue distribution of GRKA4 and GRK4B
      suggests that individual GRK4 variants may serve distinct physiological
      functions.

PMID- 9607786
TI  - Ha-ras interference with thyroid cell differentiation is associated with a down
      regulation of thyroid transcription factor-1 phosphorylation.
AB  - Mechanisms responsible for the lack of thyroid-specific differentiation markers
      in Ha-ras transformed FRTL-5 cells have been investigated. In vivo cell labeling
      and immunoprecipitation demonstrate that phosphorylation of the thyroid
      transcription factor-1 (TTF-1) is clearly reduced in thyroid cells transformed
      with the Ha-ras oncogene. Fingerprinting analysis of phosphotryptic peptides from
      FRTL-5 and Ha-ras-FRTL-5 cells also reveals a heterogeneous pattern of TTF-1
      phosphorylation in the transformed cell line. This heterogeneity is localized in
      the amino terminal cluster of phosphoserines, as determined by transfection of
      HeLa cells with TTF-1 mutants in which serine residues have been replaced by
      alanines. Amplification and nucleotide sequence of the 5'-coding region of the
      TTF-1 gene in Ha-ras-FRTL-5 cells rule out the possibility that differences in
      phosphorylation were the consequence of any mutational event affecting residues
      within the N-terminal protein sequence. Hypophosphorylated TTF-1 is still able to
      bind its DNA consensus sequence within the thyroglobulin promoter, although a
      reporter construct whose expression is exclusively dependent on TTF-1 is not
      transactivated. Transfection of Ha-ras-FRTL-5 cells with an expression vector
      encoding the cAMP dependent protein kinase A (PKA) catalytic subunit partially
      reestablishes TTF-1 transcriptional activity. Taken together, these results
      indicate that the lack of specific thyroid gene expression in Ha-ras-FRTL-5 cells
      could be a direct consequence of the inability of TTF-1 to promote transcription.

PMID- 9607787
TI  - Changes in fetal plasma corticotropin-releasing hormone during androstenedione
      induced labor in the rhesus monkey: lack of an effect on the fetal hypothalamo
      pituitary-adrenal axis.
AB  - Androstenedione infusion to pregnant monkeys leads to premature labor and live
      delivery. Androstenedione-induced labor also increased placental CRH messenger
      RNA and peptide to concentrations observed at term in pregnant monkeys. Placental
      CRH may modulate fetal pituitary-adrenal function during pregnancy in primates.
      This study tested the hypothesis that androstenedione-induced premature delivery
      in pregnant monkeys results from androstenedione-induced increases in placental
      CRH, which stimulate premature activation of the fetal pituitary-adrenal axis.
      The hypothesis was tested by comparing fetal umbilical vein (FUV) plasma CRH,
      ACTH, dehydroepiandrosterone sulfate, and cortisol concentrations at cesarean
      section in fetuses from mothers undergoing spontaneous, term labor (group I),
      with those in fetuses from mothers undergoing androstenedione-induced, premature
      labor (group II) and with those from mothers not in labor (group III). In
      addition, gestation-related changes in maternal plasma CRH concentrations were
      investigated, and CRH immunoactivity was characterized by Sephadex G50
      chromatography in pooled maternal plasma extracts. FUV CRH concentrations were
      similarly elevated in group I and group II fetuses, compared with group III
      fetuses. Despite similar FUV blood gases in all fetuses, FUV ACTH and
      dehydroepiandrosterone sulfate concentrations were higher in group I fetuses than
      in group II or group III fetuses. The majority of CRH immunoactivity coeluted
      with synthetic human CRH. Maternal plasma CRH concentrations showed a modest
      increase with gestation in the rhesus monkey. These data: 1) demonstrate that
      androstenedione treatment of pregnant monkeys at 0.8 of gestation elevates fetal
      plasma CRH to similar concentrations measured at term; 2) do not support the
      hypothesis that androstenedione-induced delivery in the monkey results from
      premature activation of the fetal pituitary-adrenal axis by placental CRH; but 3)
      do support a role for activation of the fetal hypothalamo-pituitary-adrenal axis
      in association with spontaneous term labor in the monkey; and 4) demonstrate
      important interprimate species differences in maternal CRH physiology.

PMID- 9607788
TI  - Effects of glucagon-like peptide 1 on the kinetics of glycogen synthase a in
      hepatocytes from normal and diabetic rats.
AB  - Glucagon-like peptide 1(7-36)amide (GLP-1) is currently under investigation as a
      possible tool in the treatment of non-insulin-dependent diabetes mellitus. In
      addition to enhancing nutrient-stimulated insulin release, the peptide also
      favors glycogen synthesis and glucose use in liver, muscle, and adipose tissue.
      GLP-1 also activates glycogen synthase a in hepatocytes from both normal and
      diabetic rats. In the present study, the kinetic aspects of such an activation
      were investigated in hepatocytes from normal rats and from animals rendered
      diabetic induced by injection of streptozotocin, either in the adult age (insulin
      dependent diabetes mellitus model) or in days 1 or 5 after birth (non-insulin
      dependent diabetes mellitus models). GLP-1 increased, in a dose-dependent manner,
      glycogen synthase a activity in the hepatocytes from all groups studied. The
      activation of the enzyme reached a steady state within 1 min exposure to GLP-1,
      which, at 10(-12) M, caused a half-maximal activation. When comparing fed vs.
      overnight-starved normal rats, a somewhat lower basal activity of glycogen
      synthase a in fasted animals (P < 0.05) coincided with a greater relative
      increment in reaction velocity in response to GLP-1. The basal activity of
      glycogen synthase a and the relative extent of its inhibition by glucagon or
      activation by insulin and GLP-1 were modulated by the extracellular concentration
      of D-glucose. The activation of glycogen synthase a by either insulin or GLP-1
      resulted not solely in an increase in maximal velocity but also in a decrease in
      affinity of the enzyme for uridine diphosphate-glucose; in diabetic animals, the
      capacity of insulin or GLP-1 to increase the maximal velocity and Michaelis
      Menten constant were less marked than in normal rats. In conclusion, this study
      indicates that the GLP-1-induced activation of glycogen synthase a displays
      attributes of rapidity, sensitivity, and nutritional dependency that are well
      suited for both participation in the physiological regulation of enzyme activity
      and therapeutic purpose.

PMID- 9607789
TI  - Regulation of pituitary follistatin and inhibin/activin subunit messenger
      ribonucleic acids (mRNAs) in male and female rats: evidence for inhibin
      regulation of follistatin mRNA in females.
AB  - The regulation of FSHbeta messenger RNA (mRNA) expression is complex and involves
      signals from the hypothalamus and gonads. Additionally, the local (pituitary)
      production of activin and follistatin appears to serve as an important modulator
      of endocrine signals for FSHbeta regulation. The purpose of these studies was to
      identify factors controlling pituitary activin/inhibin subunit and follistatin
      mRNA production in male and female rats. Both males and females expressed the
      follistatin, inhibin alpha, and betaB mRNAs, whereas the betaA mRNA was not
      detected. In males, levels of FSHbeta and follistatin were higher than those in
      females. After gonadectomy, levels of FSHbeta and follistatin increased in both
      sexes, whereas betaB rose only in females. In males, blockade of GnRH action from
      the time of castration prevented the increase in FSHbeta and follistatin,
      suggesting that GnRH is the primary stimulus for these gene products. In females,
      treatment with a GnRH antagonist only partially prevented the rise in FSHbeta,
      follistatin, and betaB expression, suggesting that other factors were also
      important. Passive immunoneutralization of circulating inhibin increased FSHbeta
      and follistatin (but not betaB), providing evidence that inhibin is a
      physiological regulator of follistatin. Replacement of estradiol at the time of
      ovariectomy prevented the increase in betaB mRNA, suggesting that gonadal
      steroids may also act via local factors to regulate FSHbeta. In summary, these
      studies provide evidence that GnRH, gonadal steroids, and gonadal peptides
      probably regulate FSHbeta expression at least in part via the intrapituitary
      activin/follistatin system.

PMID- 9607790
TI  - Tissue distribution, turnover, and glycosylation of the long and short growth
      hormone receptor isoforms in rat tissues.
AB  - Two isoforms of the GH receptor, the full-length receptor (GHRL) and a short
      isoform (GHRS) that lacks the transmembrane and intracellular domains of GHRL,
      have been analyzed in rat tissue extracts by Western blotting and
      immunoprecipitation. Although quantitative estimates of GHRS and GHRL based on
      coprecipitation of [125I]GH indicated similar amounts of both isoforms in tissue
      extracts, the 110 kDa band corresponding to GHRL was generally not detected on
      Western blots without enrichment by immunoprecipitation. Two bands with
      electrophoretic mobilities corresponding to 38 and 42 kDa were present in
      extracts prepared from liver, muscle, and adipocytes. Western blots of the GH
      binding protein in rat serum also revealed two bands, but these had
      electrophoretic mobilities corresponding to 44 and 52 kDa. After digestion by
      endoglycosidase F, a single band with an electrophoretic mobility corresponding
      to 31 kDa was detected in samples from adipocytes, liver or serum, indicating
      that GHRS retained in tissues is glycosylated less extensively than that in rat
      serum. Digestion with neuraminidase indicated that the smaller glycoproteins in
      tissue extracts lack sialic acid residues that are present in serum samples.
      Furthermore, endoglycosidase H degraded GHRS in liver extracts to a 31 kDa band
      but did not degrade serum samples, suggesting that tissues retain a high mannose
      form of GHRS. The abundance of GHRS or GHRL in tissues from male, virgin female,
      and pregnant rats was estimated from the amount of 125I-GH that was bound to each
      isoform after immunoprecipitation. Liver contained more than 10 times as much
      GHRS per gram of tissue as fat or muscle. In liver, muscle, and fat, the amount
      of GHRS exceeded that of GHRL, sometimes by as much as 6-fold. GHBP levels in
      serum of females exceeded those in males, and rose even higher in pregnant
      females. The abundance of GHRS in all tissue extracts paralleled serum levels. In
      muscle and fat, the levels of GHRL did not differ in male, female and pregnant
      rats, whereas in liver, the pattern was similar to the GHRS pattern. In all
      tissues, pools of GHRS exceeded those of GHRL by a factor that grew larger as
      tissue and serum levels increased. The half life of GHBP in serum was estimated
      to be 2.4 h in rats treated with cycloheximide, whereas that of GHRS was 20 min
      in liver and 8.5 h in fat. These results suggest that GHRS is synthesized in
      liver 8 times faster than it is released into serum, whereas synthesis in fat is
      less than 30% of the rate at which it is released into serum by all tissues.
      Therefore, liver appears to be the major source of GHBP in serum. Although
      secretion into the circulatory system accounts for little or perhaps none of its
      turnover in some tissues, GHRS pools in tissues do appear to be regulated,
      suggesting that GHRS may function primarily in the cells in which it is
      synthesized.

PMID- 9607791
TI  - Vasopressin messenger ribonucleic acid regulation via the protein kinase A
      pathway.
AB  - Activation of vasopressin (VP) gene expression in vivo by osmotic stimuli results
      in an increase in both messenger RNA (mRNA) content and polyadenylate [poly(A)]
      tail length. VP gene transcription in vitro is stimulated by protein kinase A
      (PKA) activation. To examine the role of PKA in the regulation of VP mRNA poly(A)
      metabolism, constructs of the rat VP gene were permanently transfected into the
      mouse anterior pituitary cell line, AtT-20. Treatment with forskolin of cells
      expressing the intact VP gene resulted in increased VP gene transcription, an
      increase in the content of VP mRNA, and a shift toward VP mRNA species with
      longer poly(A) tails accompanied by the loss of VP mRNA species with shorter
      poly(A) tails. We uncoupled the PKA-stimulated appearance of long-tailed species
      from the disappearance of short-tailed species, suggesting that the size shift
      was caused by a coincident, but uncoupled net increase in VP mRNA species with
      elongated poly(A) tails and net loss of mRNA species with short poly(A) tails.
      These data indicate that activation of the PKA second-messenger pathway both
      enhances transcription of the VP gene and causes an increase in the average
      length of VP mRNA poly(A) tails. This latter effect, by shifting upwards the
      average poly(A) tail size, could result in increased translational efficiency or
      stability of VP mRNA, thereby providing an additional mechanism by which PKA may
      enhance gene expression.

PMID- 9607792
TI  - The ontogeny of glucocorticoid negative feedback: influence of maternal
      deprivation.
AB  - Glucocorticoid feedback can be viewed as having two modes of operation: proactive
      and reactive. "Proactive" feedback maintains basal activity of the hypothalamic
      pituitary-adrenal axis, whereas the termination of stress-induced hypothalamic
      pituitary-adrenal activity is facilitated by "reactive" feedback. In the present
      study we studied the ontogeny of both feedback modes and tested the hypothesis
      that the development of feedback depends on mother-pup interaction. On postnatal
      day 9 or 12, pups were deprived (DEP) of the dam for 24 h; nondeprived pups of
      the same age served as controls. The pups were adrenalectomized (ADX) at the end
      of deprivation and given corticosterone (CORT) replacement by either injection or
      pellet implants using the following two designs: first at the time of
      adrenalectomy (ADX) to test the role of CORT in the maintenance of basal ACTH
      levels, and then 3 h after ADX, to investigate CORT suppression of elevated ACTH
      levels induced by prior ADX. Regarding proactive feedback, the results showed
      that injection of CORT at the time of ADX was only partially effective in
      preventing ACTH elevations, whereas CORT pellets maintained basal levels of ACTH
      in all ADX pups. The reactive mode of negative feedback in nondeprived pups was
      resistant to CORT injection, whereas the CORT pellet resulted in a return to
      basal levels within 60 min. Maternal deprivation did not affect proactive
      feedback, but caused a more sustained increase in ACTH levels and a failure to
      return to basal levels 3 h after ADX despite significantly higher levels of
      circulating CORT in these DEP pups. It is concluded that 1) proactive and
      reactive modes of negative feedback are operative, provided the pups are
      maintained on chronic replacement with CORT; 2) DEP impairs the reactive, rather
      than the proactive, mode of feedback inhibition in the neonate.

PMID- 9607793
TI  - Expression and microvillar localization of scavenger receptor, class B, type I (a
      high density lipoprotein receptor) in luteinized and hormone-desensitized rat
      ovarian models.
AB  - Steroidogenic cells in rats and mice obtain most of their cholesterol for steroid
      production and cholesteryl ester (CE) storage via the selective uptake pathway in
      which high density lipoprotein CE (HDL-CE) is taken into the cell without the
      uptake and degradation of the HDL particle. A number of recent studies show that
      the scavenger receptor, class B, type I (SR-BI) can mediate HDL-CE selective
      uptake in cultured cells and suggest that this receptor may be responsible for
      HDL-CE selective uptake in steroidogenic cells in vivo. In the current study we
      examine the relationship between SR-BI expression and HDL-CE selective uptake in
      the gonadotropin-primed, luteinized rat ovary and in the ovary that is
      desensitized by multiple gonadotropin treatments. Results from this study
      demonstrate a tight association between expression of SR-BI and measurements of
      HDL-CE selective uptake regardless of the steroidogenic state of the ovary. Thus,
      in the luteinized ovary (which is actively producing progestins), HDL-CE
      selective uptake is high, as is the expression of SR-BI. In the desensitized
      ovary (where CE content is reduced by 90% and progestin production is virtually
      absent), HDL-CE selective uptake and SR-BI are induced 2- to 3-fold compared with
      those in the luteinized ovary. These data argue that SR-BI can be regulated by
      the cholesterol status of the luteal cell independently of gonadotropic
      stimulation. Immunostaining at the light microscopic level showed strong
      expression of SR-BI specifically on the surface of luteal cells in the luteinized
      and desensitized ovary. Immunolocalization at the electron microscopic level
      showed that SR-BI was associated with microvilli and microvillar channels of the
      luteal cell surface. This result supports the hypothesis that microvilli and
      microvillar channels represent a cell surface compartment that is specialized for
      the selective uptake of lipoprotein cholesterol into steroidogenic cells.

PMID- 9607794
TI  - Endogenous opioid peptides contribute to suckling-induced prolactin release by
      suppressing tyrosine hydroxylase activity and messenger ribonucleic acid levels
      in tuberoinfundibular dopaminergic neurons.
AB  - The endogenous opioid peptides have been implicated in the control of the
      suckling-induced PRL rise during lactation. This study examined the role of the
      endogenous opioid peptides in suppressing tuberoinfundibular dopaminergic
      neuronal activity during lactation. In the first experiment, lactating rats were
      constantly exposed to pups. Naloxone (NAL; 60 mg/kg x h; i.v.), an opioid
      receptor antagonist, or saline was infused for 12 h. Blood was collected before
      and at 2-h intervals during the infusion. NAL suppressed circulating PRL levels
      to less than 36% of control values at 4, 6, 8, and 12 h after the onset of the
      infusion. Tyrosine hydroxylase (TH) activity in the stalk-median eminence and TH
      messenger RNA signal levels in the arcuate nucleus were determined at the end of
      the NAL infusion. TH activity and TH messenger RNA signal levels were increased
      2.5- and 2.7-fold, respectively, after the 12-h NAL infusion. Even though the
      time spent with their pups was similar between the two groups, the pups in the
      NAL-treated group failed to gain weight during the 12-h NAL infusion period,
      whereas the control litters (8 pups) gained 5 g. In a second experiment, pups
      were removed from the dams before the 12-h NAL infusion and were returned after
      11 h. Blood was collected before the infusion, at 3-h intervals during the pup
      separation period, and at 15-min intervals after reunion with the pups. Plasma
      PRL in control and NAL-treated rats was low (1-15 ng/ml) and similar during the
      separation period. The suckling-induced PRL surge in NAL-treated rats was
      markedly attenuated to 9-25% of control levels (350-650 ng/ml). After a 1-h
      suckling episode, TH activity in the stalk-median eminence of NAL-treated rats
      was 4.5-fold greater than controls. Litter weight gains were significantly less
      in NAL-treated rats during the 1-h suckling episode. These data indicate that the
      endogenous opioid peptides are an integral component for increasing PRL release
      in response to suckling and they act to decrease tuberoinfundibular dopaminergic
      neuronal activity during lactation, in part, by suppressing TH gene expression.

PMID- 9607795
TI  - Tumor necrosis factor-alpha inhibits leydig cell steroidogenesis through a
      decrease in steroidogenic acute regulatory protein expression.
AB  - The aim of the present study was to identify the sites of the inhibitory action
      of TNFalpha (tumor necrosis factor alpha) on LH/hCG-stimulated testosterone
      formation. By using cultured porcine Leydig cells as a model, TNFalpha was shown
      to inhibit testosterone secretion when testicular cells were stimulated with hCG
      but not when incubated with 22R-hydroxycholesterol (a cholesterol substrate
      derivative that readily passes through cell and mitochondrial membranes). Such an
      observation suggested that the cytokine may affect cholesterol transport and/or
      availability to cytochrome P450scc in the mitochondria. Specifically, we report
      here that TNFalpha reduced in a dose- and time-dependent manner hCG-induced StAR
      (steroidogenic acute regulatory protein) levels. The maximal and half-maximal
      effects were obtained with 20 ng/ml (1.2 nM) and 1.6 ng/ml (0.09 nM) of TNFalpha,
      respectively. Maximal inhibitory effects of TNFalpha on StAR messenger RNA and
      protein levels were obtained after 48 h of treatment. Additionally, the presence
      of TNFalpha receptors P55 in terms of protein (identified through cross-linking
      experiments) and messenger RNA (identified through RT-PCR analysis) suggested
      that the effects of the cytokine are directly exerted on the testicular
      steroidogenic cell type.

PMID- 9607796
TI  - Interactive mechanisms among pituitary adenylate cyclase-activating peptide,
      vasoactive intestinal peptide, and parathyroid hormone receptors in guinea pig
      cecal circular smooth muscle cells.
AB  - Vasoactive intestinal peptide (VIP) causes relaxation of smooth muscle cells via
      both VIP-specific receptor coupled to nitric oxide synthase and VIP-preferring
      receptor coupled to adenylate cyclase. Because the mechanism of interaction among
      VIP, pituitary adenylate cyclase-activating peptide (PACAP), and PTH is still
      unclear, the characteristics of the receptors for PACAP and PTH in circular
      muscle cells obtained from the guinea pig cecum were investigated. The effects of
      an inhibitor of cAMP-dependent protein kinase [cyclic adenosine 3',5'
      monophosphorothioate (Rp-cAMPS)], guanylate cyclase inhibitors, antagonists of
      these peptides, and the selective receptor protection on the relaxing effect
      produced by PACAP, VIP, and PTH were examined. PACAP-induced relaxation was
      significantly inhibited by a VIP antagonist, a PTH antagonist, Rp-cAMPS, and an
      inhibitor of particulate guanylate cyclase. VIP-induced relaxation was
      significantly inhibited by a PACAP antagonist and a PTH antagonist. PTH-induced
      relaxation was significantly inhibited by a VIP-specific receptor antagonist and
      Rp-cAMPS, but not by a PACAP antagonist. A PTH antagonist significantly inhibited
      a VIP-preferring receptor agonist-induced relaxation. The muscle cells in which
      cholecystokinin octapeptide and PTH receptors were protected completely abolished
      the inhibitory responses to VIP and PACAP. The muscle cells in which
      cholecystokinin octapeptide and VIP or PACAP receptors were protected completely
      abolished the inhibitory response to PTH. This study shows that PACAP induces
      relaxation of these muscle cells via both VIP-preferring receptor coupled to
      adenylate cyclase and PACAP-specific receptor, and that PTH induces relaxation of
      the muscle cells via PTH-specific receptor coupled to adenylate cyclase. In
      addition, the results of a selective receptor protection show that PTH does not
      bind to VIP receptors, and that VIP does not bind to PTH receptor. Therefore,
      this study first demonstrates the presence of one-way inhibitory mechanisms from
      the PTH-specific receptor to the VIP-preferring receptor, and from the VIP
      specific receptor to the PTH-specific receptor in the mechanisms of interaction
      between VIP and PTH.

PMID- 9607797
TI  - Fasting-induced increase in type II iodothyronine deiodinase activity and
      messenger ribonucleic acid levels is not reversed by thyroxine in the rat
      hypothalamus.
AB  - The importance of local formation of T3 in the feedback effect of the thyroid
      gland on hypothalamic TRH-producing cells has been established. Primary failure
      of the thyroid gland results in a fall in circulating T4 and T3 levels, leading
      to an elevation in the production and release of TRH in the hypothalamic
      paraventricular nucleus. In contrast, during short term fasting, declining plasma
      levels of thyroid hormones coincide with suppressed TRH production and release.
      In the brain, the prevalent enzyme that converts T4 to T3 is type II
      iodothyronine deiodinase (DII). The present study was undertaken to determine
      whether a differential hypothalamic expression of type II deiodinase may exist in
      fasted rats and in animals that are hypothyroid due to the failure of the thyroid
      gland. Using in situ hybridization, we assessed type II deiodinase messenger RNA
      (mRNA) levels in the hypothalamus of rats that were control euthyroid,
      hyperthyroid (T4), hypothyroid induced by propylthiouracil (PTU), and fasted. A
      group of fasted rats also received exogenous T4. DII mRNA was detected around the
      third ventricle, including the ependymal layer and adjacent periventricular
      regions as well as in the arcuate nucleus and the external layer of the median
      eminence. Quantitative in situ hybridization analysis demonstrated that PTU
      treatment and short term fasting resulted in significant elevations in DII
      messenger levels compared with those in euthyroid controls. Three weeks of PTU
      administration induced a consistent decline in circulating T3 and undetectable T4
      levels, whereas 3 days of fasting resulted in only a 50% fall in the
      concentration of serum thyroid hormones. Interestingly, however, the expression
      of the DII mRNA was more than 2-fold higher in fasted animals compared with the
      values in PTU-treated rats. Furthermore, although T4 administration repressed DII
      mRNA expression in euthyroid animals, the same treatment had no effect on the
      fasting-induced elevations of DII message. To assess whether DII enzymatic
      activity is also affected during food deprivation, hypothalami were dissected
      out, and DII activity was measured in control euthyroid, fasted, and fasted plus
      T4-treated rats. To determine whether comparable changes in plasma thyroid
      hormone levels induced by fasting and PTU treatment could have affected DII
      enzymatic activity in a similar manner, animals were injected ip with PTU for 5
      days to decrease plasma thyroid hormones to levels similar to those caused by
      fasting. DII enzymatic assay showed a significant increase in DII activity in
      fasted and fasted plus T4-treated animals compared with those in euthyroid
      controls and PTU-treated rats. No significant changes were found in PTU-treated
      rats compared with euthyroid animals. These data indicate that during short term
      fasting, a signal of nonthyroid origin underlies the robust elevation of DII
      production and activity in the hypothalamus. Thus, we propose that during the
      initial phase of food deprivation, an increased negative thyroid feedback exists
      on the hypothalamus due to locally formed T3. This local hyperthyroidism may, in
      turn, induce the suppression of TRH under these conditions.

PMID- 9607798
TI  - Differential metabolite accumulation may be the cause of strain differences in
      sensitivity to streptozotocin-induced beta cell death in inbred mice.
AB  - Inbred strains of mice vary in their sensitivity to the diabetogenic effects of
      streptozotocin (STZ). To investigate the basis for this strain difference we
      exposed islet cells from two strains of mice that differ in sensitivity to the
      drug. We examined them morphologically and measured islet NAD + NADH content,
      streptozotocin metabolite accumulation, glucose transport capacity, Glut2 levels
      and medium nitrite accumulation. C57bl/6J mice were more sensitive to STZ than
      Balb/c mice as judged by the extent of pancreatic insulin depletion and beta cell
      death, in vivo and in vitro. The mode of cell death was necrosis. After a 30-min
      in vitro exposure to the drug the more sensitive C57bl/6J islets contained higher
      levels of streptozotocin metabolites and less NAD + NADH than the more resistant
      Balb/c islets. The lack of any strain differences in 3-O-methyl glucose
      transport, Glut2 levels and medium nitrite accumulation suggested that STZ
      transport and nitric oxide metabolism were not responsible for differences in STZ
      sensitivity and metabolite accumulation. Thus the strain differences in STZ
      sensitivity appears to be due to intracellular events within the beta cell
      occurring after STZ transport and before NAD + NADH depletion. STZ metabolite
      accumulation appears to be associated with STZ sensitivity. Further studies are
      warranted to determine if differential STZ metabolite accumulation is responsible
      for STZ sensitivity.

PMID- 9607799
TI  - Mutant alpha-subunit of the G protein G12 activates proliferation and inhibits
      differentiation of 3T3-F442A preadipocytes.
AB  - We studied the G protein alpha-subunit Galpha12 in various tissues and cell
      lines. Significant amounts of Galpha12 were detected by immunoblots in liver,
      chromaffin cells, RINm5F cells, 3T3-F442A cells, and preadipocytes, but not in
      adipocytes, sperm, kidney, NB2A cells, or brain. To study the role of Galpha12 in
      adipose tissue differentiation, the preadipocyte cell line 3T3-F442A was
      transfected with wild-type Galpha12 or a constitutively activated mutant of
      Galpha12. Stable expression of the activated mutant of Galpha12 stimulated cell
      growth and inhibited preadipocyte differentiation. In contrast, wild-type
      Galpha12 overexpression inhibited preadipocyte differentiation, without any
      effect on cell proliferation. The role of Galpah12 on the Raf/MEK/mitogen
      activating protein kinase (MAPK) cascade was studied. In confluent preadipocytes,
      expression of the activated mutant of Galpha12 induced an increase in B-Raf
      expression, but no change in MAPK activity. Differentiation was associated with a
      decrease in MAPK activity in control 3T3-F442A cells. Wild-type Galpha12
      overexpression prevented the decrease in MAPK activity and induced MEK1, but not
      B-Raf, expression. Moreover, the activated mutant of Galpha12 induced an increase
      in MAPK activity and in the expression of both MEK1 and B-Raf. These data
      indicate that the activated mutant of Galpha12 stimulates the proliferation of
      3T3-F442A preadipocytes, possibly through an increase in B-Raf expression,
      independently of the MEK/MAPK pathway, but prevents differentiation, probably
      through an increase in MEK1 expression and MAPK activity.

PMID- 9607800
TI  - Effects of fibroblast growth factor-2 on longitudinal bone growth.
AB  - In vivo, fibroblast growth factor-2 (FGF-2) inhibits longitudinal bone growth.
      Similarly, activating FGF receptor 3 mutations impair growth in achondroplasia
      and thanatophoric dysplasia. To investigate the underlying mechanisms, we chose a
      fetal rat metatarsal organ culture system that would maintain growth plate
      histological architecture. Addition of FGF-2 to the serum-free medium inhibited
      longitudinal growth. We next assessed each major component of longitudinal
      growth: proliferation, cellular hypertrophy, and cartilage matrix synthesis.
      Surprisingly, FGF-2 stimulated proliferation, as assessed by [3H]thymidine
      incorporation. However, autoradiographic studies demonstrated that this increased
      proliferation occurred only in the perichondrium, whereas decreased labeling was
      seen in the proliferative and epiphyseal chondrocytes. FGF-2 also caused a marked
      decrease in the number of hypertrophic chondrocytes. To assess cartilage matrix
      synthesis, we measured 35SO4 incorporation into newly synthesized
      glycosaminoglycans. Low concentrations (10 ng/ml) of FGF-2 stimulated cartilage
      matrix production, but high concentrations (1000 ng/ml) inhibited matrix
      production. We conclude that FGF-2 inhibits longitudinal bone growth by three
      mechanisms: decreased growth plate chondrocyte proliferation, decreased cellular
      hypertrophy, and, at high concentrations, decreased cartilage matrix production.
      These effects may explain the impaired growth seen in patients with
      achondroplasia and related skeletal dysplasias.

PMID- 9607801
TI  - Differential spatiotemporal regulation of lactoferrin and progesterone receptor
      genes in the mouse uterus by primary estrogen, catechol estrogen, and
      xenoestrogen.
AB  - Many xenobiotics are considered reproductive toxins because of their ability to
      interact with the nuclear estrogen receptors (ERalpha and ERbeta). However, there
      is evidence that these xenobiotics can regulate gene expression in the
      reproductive targets by mechanisms that do not involve these ERs. To examine this
      further, we compared the effects of estrogenic (o,p'-DDT [1-(o-chlorophenyl)-1-(p
      chlorophenyl)2,2,2-trichloroethane] and Kepone, chlordecone) and nonestrogenic
      (p,p'-DDD [1,1-dichloro-2,2-bis(p-chlorophenyl)ethane], a metabolite of p,p'-DDT)
      xenobiotics with those of 17beta-estradiol (E2) and 4-hydroxyestradiol-17beta (4
      OH-E2), a catechol metabolite of E2, on uterine expression of lactoferrin (LF)
      and progesterone receptor (PR). These genes are estrogen responsive in the mouse
      uterus. Normally, LF is expressed in the uterine epithelium, whereas PR is
      expressed in both the epithelium and stroma in response to estrogenic
      stimulation. Ovariectomized mice were injected with xenobiotics (7.5 mg/kg), E2
      (10 microg/kg), 4-OH-E2 (10 microg/kg), or the vehicle (oil, 0.1 ml/mouse), and
      uterine tissues were processed for Northern blot and in situ hybridization. The
      pure antiestrogen ICI-182780 (ICI; 1 or 20 mg/kg) was used to interfere with
      estrogenic responses that were associated with the ERs. The results of Northern
      and in situ hybridization demonstrated increased uterine levels of PR and LF
      messenger RNAs (mRNAs) by all of these xenobiotics, but quantitatively the
      responses were much lower than those induced by E2 or 4-OH-E2. The results
      further showed that the E2-inducible epithelial LF mRNA accumulation was markedly
      abrogated by pretreatment with ICI (20 mg/kg). In contrast, this treatment
      retained the epithelial expression of PR mRNA, but down-regulated the stromal
      expression. In contrast, ICI had negligible effects on LF and PR mRNA responses
      to 4-OH-E2, indicating that this catechol estrogen exerted its effects primarily
      via a mechanism(s) other than the ERs. The heightened accumulation of LF mRNA in
      the epithelium in response to Kepone and o,p'-DDT was also severely compromised
      by pretreatment with ICI, but this antiestrogen had little effect on responses to
      p,p'-DDD. Similar to E2, Kepone increased the expression of PR mRNA in both
      uterine epithelium and stroma. However, pretreatment with ICI decreased stromal
      cell expression, whereas epithelial cell expression remained unaltered or
      increased. These responses were not noted in mice treated with o,p'-DDT or p,p'
      DDD. Collectively, the results demonstrate that catechol estrogens or xenobiotics
      can alter uterine expression of estrogen-responsive genes by mechanisms that are
      not totally mediated by the classical nuclear ERs, and these alterations are cell
      type specific. We conclude that an interaction of a compound with the nuclear
      ERalpha and/or ERbeta is not an absolute requirement for producing specific
      estrogen-like effects in the reproductive target tissues.

PMID- 9607802
TI  - Reconstitution of estrogen-dependent transcriptional activation of an adenoviral
      target gene in select regions of the rat mammary gland.
AB  - Estrogen regulates proliferation and morphogenesis of mammary ductal epithelium
      by interacting with a specific intracellular estrogen receptor (ER) that acts as
      a hormone-dependent transcriptional regulator of gene expression. The mechanisms
      by which ER regulates transcription in response to estrogen have been analyzed
      extensively in tissue culture and in cell-free systems. These studies have
      demonstrated that the transcriptional activity of ER is strongly influenced by
      cellular context and highlight the need to address ER transcriptional activity in
      an appropriate cellular background. Thus, to gain insight into the mechanistic
      role of ER in mammary epithelial morphogenesis, we have used an adenoviral gene
      delivery strategy to introduce an estrogen-responsive reporter gene into the
      mammary epithelium and to monitor the activity of endogenous ERs in their natural
      environment where cellular context including stromal-epithelial interactions can
      be taken into account. Using this approach, we first demonstrated highly
      efficient adenoviral delivery throughout the mammary epithelium using a beta
      galactosidase (betagal) reporter gene under the control of the constitutively
      active cytomegalovirus (CMV) promoter. Next, we constructed an adenoviral vector
      by substituting the CMV promoter with an estrogen-dependent promoter fragment
      linked betagal (Ad-ERE-tk-betagal). This adenoviral reporter system provides
      evidence that ER positive mammary epithelial cells display a differential
      sensitivity in a region-specific manner toward estrogen induction. Our data
      suggest that the availability of factor(s) other than ER is necessary for ER
      mediated gene activation and may be important in modulating the differential
      responses of mammary epithelial cells to estrogen.

PMID- 9607803
TI  - Expression and effect of insulin-like growth factor I on rat fetal Leydig cell
      function and differentiation.
AB  - Insulin like growth factor I (IGF-I) is believed to be a potent para/autocrine
      stimulator of Leydig cell function in adult testis. We investigated whether IGF-I
      is also an intratesticular regulator of fetal Leydig cell function by measuring
      its production in the fetal testis and its ability to affect testicular
      steroidogenesis during fetal development. Northern blot analysis revealed one
      major IGF-I transcript of 7-7.5 kb and two minor transcripts of 3.8 and 1.8 kb in
      20.5 day fetal testis. IGF-I was detected by RIA in 16.5 fetal day testes, and
      the amounts of IGF-I secreted by 16.5 and 20.5 fetal day testes in vitro were
      much greater than the amounts contained in the testes, indicating active
      synthesis in culture. The secretion of IGF-I by the fetal testis in vitro was
      increased with testicular age and time in culture. It was not modified by
      gonadotropins or (Bu)2cAMP. Testosterone secretion by fetal testes explanted
      13.5, 16.5, 18.5, and 20.5 days after conception and cultured in the presence or
      absence of 100 ng/ml LH for 3 days was not affected by the addition of 50 ng/ml
      IGF-I to the medium. In contrast, the addition of IGF-I to dispersed fetal
      testicular cells cultured for 3 days in the presence or absence of LH increased
      the number of Leydig cells identified by a positive cytochemical reaction for
      3beta-hydroxysteroid dehydrogenase (3betaHSD). This was more pronounced with
      cells from 16.5- day-old fetuses (stage when the fetal Leydig cells are
      differentiating in vivo) than with 20.5-day-old fetuses cells (stage when the
      number and the function of fetal Leydig cells are stable or decreasing). It
      results from both an increased differentiation of mesenchymal cells in fetal
      Leydig cells and an increase in the mitotic index of the fetal Leydig cells, as
      inferred from the small increase in the percentage of bromodeoxyuridine/3betaHSD
      positive cells. Both LH and IGF-I increased significantly testosterone production
      by day 16.5 cells. In the presence of LH, a high amount of testosterone was
      produced per 3betaHSD-positive cell; IGF-I further increased this production.
      This effect was not observed with day 20.5 cells. The amounts of testosterone
      produced per 3betaHSD-positive cell cultured in the presence of both LH and IGF-I
      were more than additive. Like IGF-I, insulin (50 ng/ml) increased testosterone
      secretion per 3betaHSD-positive cells in cultures of day 16.5 cells, but not in
      those of day 20.5, cells. Lastly, IGF-I also increased the steroidogenic activity
      of each Leydig cell in cultures containing (Bu)2cAMP, but its effects were weaker
      than those observed in the presence of LH. This suggests that IGF-I has sites of
      action both upstream and downstream cAMP generation. These results suggest that
      IGF-I acts as paracrine/autocrine factor in the differentiation and activity of
      fetal Leydig cells.

PMID- 9607804
TI  - Changing patterns of gene expression identify multiple steps during regression of
      rat prostate in vivo.
AB  - The rat ventral prostate is an androgen-dependent organ that undergoes dramatic
      cell death upon removal of testosterone by surgical castration. Several well
      characterized criteria, such as nuclear condensation, organelle blebbing, and DNA
      fragmentation, have been used to demonstrate that most of this cell loss is due
      to programmed cell death, or apoptosis, of the secretory epithelial cells. In
      addition to changes in morphology, it is well known that cells undergoing
      apoptosis show alterations in gene expression, and it is widely assumed that many
      of these genes are directly involved in the mechanism of programmed cell death.
      Using poly A+ RNA derived from normal rat prostate as well as from the regressing
      prostates of castrated rats, we have used a PCR-based subtractive hybridization
      approach to generate complementary DNA (cDNA) libraries greatly enriched in cDNAs
      strongly regulated during rat prostate regression. Several hundred of the genes
      represented in these libraries appear to be strongly regulated during prostate
      regression and most of these are prostate specific. Sequence analysis indicates
      that up to 30% of these clones are similar or identical to genes of known
      function, approximately 20% are similar to expressed sequence tags (ESTs), and as
      many as 50% of these clones have not been characterized previously. Analysis of
      selected clones using in situ hybridization indicates that they are expressed
      specifically in prostate epithelial cells, and that certain of these clones are
      regulated temporally in a pattern consistent with apoptosis. The patterns of gene
      expression include: 1) genes whose expression decreases uniformly after removal
      of androgen, indicative of androgen sensitive genes; 2) genes whose expression
      increases in apoptotic prostate cells and in other tissues, suggesting a class of
      genes generally involved in apoptosis; 3) and genes whose expression increases in
      individual regressing prostate epithelial cells, suggesting a class of prostate
      specific genes associated with apoptosis.

PMID- 9607805
TI  - The role of nitric oxide in oocyte meiotic maturation and ovulation: meiotic
      abnormalities of endothelial nitric oxide synthase knock-out mouse oocytes.
AB  - Evidence supports the involvement of nitric oxide (NO) in ovulation,
      steroidogenesis, and atresia-related apoptosis. This study was designed to
      investigate the role of endothelial nitric oxide synthase (eNOS)-derived NO in
      ovulation, oocyte meiotic maturation, and ovarian steroidogenesis using wild-type
      (WT) mice and mice in which the gene for eNOS had been deleted (eNOS knock-out).
      We observed that mature eNOS knock-out females have significantly fewer pups born
      in each litter and a higher mortality rate of pups than those born to
      heterozygote or WT females (P < 0.05). To determine the influence of eNOS
      deficiency on ovarian function, immature WT and eNOS knock-out mice were
      superovulated by injecting PMSG (5 IU) followed by an injection of hCG (5 IU,
      i.p.) 48 h later. To determine whether murine oocytes expressed eNOS before (0
      and 8 h post-hCG) and after ovulation (16 h post-hCG). we performed
      immunofluorescent staining. Positive specific staining for eNOS was observed on
      the surface of ovarian and ovulated oocytes obtained from WT mice, but not on
      oocytes from eNOS knock-out mice. To determine the role of eNOS-derived NO in
      ovulation, ovulated oocytes were counted 16 h post-hCG. eNOS knock-out females
      showed a significant reduction (by 63%; P < 0.0001) in ovulatory efficiency
      compared with WT females. The reduction in the ovulation rate in eNOS-deficient
      mice compared with that in WT mice was also associated with a higher
      concentration of estradiol (P < 0.01) without significant changes in the plasma
      progesterone level. eNOS deficiency impaired not only ovulation, but also oocyte
      meiotic maturation. Ovulated oocytes were classified as being in one of the
      following stages of meiosis: metaphase I, metaphase II, or showing atypical
      (degenerative) morphology. We observed that fewer oocytes from eNOS knock-out
      mice had entered metaphase II of meiosis, and a greater percentage remained in
      metaphase I or were atypical (P < 0.002) relative to those in WT mice.
      Furthermore, many oocytes that showed either a delay in meiotic maturation or
      abnormal morphology were undergoing cell death. Our results support a role for NO
      in the ovulatory process. The ovarian defects observed in the eNOS knock-out mice
      suggest that eNOS-derived NO is a modulator of oocyte meiotic maturation.

PMID- 9607806
TI  - Extranuclear localization of endogenous 11beta-hydroxysteroid dehydrogenase-2 in
      aldosterone target cells.
AB  - Type 2 11beta-hydroxysteroid dehydrogenase (11betaHSD2) plays a key role in
      conferring aldosterone selectivity on the mineralocorticoid receptor (MR) by
      inactivating intracellular glucocorticoids before they can occupy the MR.
      11betaHSD2 is a microsomal enzyme expressed in aldosterone target cells, although
      its subcellular distribution is still unclear. The goal of this study was to
      determine the subcellular localization of the endogenous 11betaHSD2 in renal
      aldosterone target cells. We generated an antibody against rabbit 11betaHSD2 and
      used it in combination with a nuclear marker and confocal laser scanning
      microscopy. On Western blots the antibody recognized a single band of
      approximately 41 kDa in the renal cortical collecting duct, outer medullary
      collecting duct, submandibular gland and adrenal cortex, whereas the colon,
      liver, renal medulla, and heart were negative. Immunohistochemistry showed
      specific reaction in the known aldosterone target cells of the kidney (connecting
      tubule, cortical collecting duct, and outer medullary collecting duct) with no
      signals over glomeruli, proximal nephron segments, and blood vessels. Staining
      for 11betaHSD2 was very weak in rabbit colon, and no immunoreactivity could be
      detected in the heart and brain. Confocal microscopy of kidney sections costained
      with the 11betaHSD2 antibody and the nuclear marker propidium iodide demonstrated
      that 11betaHSD2 is in the cytoplasmic compartment with no evidence for nuclear
      localization. Subcellular localization of 11betaHSD2 to a cytoplasmic compartment
      seems ideal for fulfilling its biological function, i.e. the efficient
      inactivation of intracellular glucocorticoids before they occupy MRs, which are
      predominantly cytoplasmic in the absence of hormone.

PMID- 9607807
TI  - Relaxin-like factor expression as a marker of differentiation in the mouse testis
      and ovary.
AB  - Expression of the relaxin-like factor (RLF) was studied at the messenger RNA
      (mRNA) and protein levels in the testes and ovaries of the mouse, as well as
      through testicular development and differentiation in the mouse testis. In situ
      hybridization or RT-PCR, and immunohistochemistry using a polyclonal antibody
      raised against a recombinant protein, provided mutually confirmatory results for
      a high expression of RLF in the Leydig cells of the adult testis and at a much
      lower level of expression in the luteal cells of the ovary through the cycle,
      pregnancy, and in lactation. Analysis of protein and mRNA expression, through
      postnatal testicular development, indicated moderate RLF expression also in the
      fetal population of Leydig cells, even in the hpg mutant mouse, lacking an active
      pituitary-gonadal axis. Prepubertal Leydig cells, however, exhibit only very low
      level RLF gene expression, this phenotype persisting in the adult hpg mouse. In
      summary, fetal Leydig cells express RLF in an LH/human CG-independent fashion,
      whereas LH/human CG is essential to induce RLF expression in the adult-type
      Leydig cell. In cultured adult Leydig cells or in the mouse tumor MA-10 cell
      line, RLF mRNA is expressed in a constitutive fashion. RLF thus seems to be a
      useful marker of Leydig cell differentiation status.

PMID- 9607808
TI  - Molecular cloning and hormonal regulation of a murine epididymal retinoic acid
      binding protein messenger ribonucleic acid.
AB  - A complementary DNA encoding the mouse epididymal secretory protein MEP 10 (mouse
      epididymal protein 10) was cloned and is now renamed murine epididymal retinoic
      acid binding protein (mE-RABP). The analysis of the predicted primary amino acid
      sequence showed that mE-RABP has a 75% identity with rat ESP I (epididymal
      secretory protein I), another epididymal retinoic acid-binding protein. The
      homology strongly suggests that mE-RABP is the mouse orthologue of rat ESP I. A
      computer analysis of the predicted three-dimensional structure confirmed that mE
      RABP can accommodate retinoic acid as ligand. In the rat, ESP I messenger RNA
      (mRNA) is expressed in the efferent ducts and in the entire caput epididymidis.
      However, in the mouse, the expression of a 950-bp mE-RABP mRNA was detected only
      in principal cells of the mid/distal caput epididymidis, suggesting that the
      regulation of region-specific expression is different in rat and mouse. Northern
      blot analyses showed that mE-RABP gene expression is no longer detected 10 days
      after castration but progressively rebounds between days 15 and 60. However, mE
      RABP protein could not be detected by Western blot 30 days after castration.
      Androgen replacement, begun 5 days after castration and continued for 4 days
      restored significant expression of mE-RABP mRNA. Efferent duct ligation for 10
      days did not affect gene expression. Taken together, these results indicate that
      mE-RABP mRNA expression is regulated by androgens but not by testicular factors.
      The overall similarity in the primary amino acid sequence of mE-RABP with ESP I
      and other members of the lipocalin superfamily suggests that they are
      evolutionarily related.

PMID- 9607809
TI  - Transcription and translation of estrogen receptor-beta in the male reproductive
      tract of estrogen receptor-alpha knock-out and wild-type mice.
AB  - Estrogen receptor-alpha (ERalpha) has been identified in the male reproductive
      tract, but the role of estrogen in the male has not been well characterized. In
      vivo mutations in ERalpha genes have demonstrated the necessity for ERalpha
      mediated action in male fertility. We asked whether both ERbeta messenger RNA and
      protein were present in the male reproductive tract of wild-type and ERalpha
      knock-out (ERalpha KO) mice, and whether ERbeta could compensate for the lack of
      ERalpha in infertile male ERalpha KO mice. Immunohistochemical localization with
      both N- and C-terminal anti-ERbeta antibodies demonstrated that ERbeta is present
      in the Leydig cells of the testes and in the epithelium of both the efferent
      ductules and the initial segment of the epididymis. RT-PCR amplification was used
      to confirm ERbeta transcription in these tissues. In conclusion, we observed that
      ERbeta messenger RNA and protein continue to be expressed in the Leydig cells,
      elongated spermatids, efferent ductules, and the initial segment of the
      epididymides of ERalpha KO mice, but the presence of ERbeta is not able to
      compensate for the absence of ERalpha in male reproductive function.

PMID- 9607810
TI  - Effects of cellular interactions on calcium dynamics in prolactin-secreting
      cells.
AB  - Signals derived from other pituitary cells can have a dramatic effect on PRL gene
      expression and secretion by mammotropes. However, the intracellular mechanisms by
      which these effects are manifested on the target cell remain unexplored. Inasmuch
      as calcium is a key modulator of both gene expression and hormone export in
      mammotropes, we evaluated the effects of cell to cell contact vs. specific
      cellular interactions on calcium dynamics within these cells. This was
      accomplished by digital-imaging fluorescence microscopy of fura-2 in pituitary
      cells that were isolated in culture (singles) or adjoining one other cell
      (doublets). After calcium imaging, we then subjected cells to immunocytochemistry
      for PRL. Doublets were further categorized into mammotropes attached to another
      mammotrope (M-M) or to a nonmammotrope (M-nonM). We then calculated and compared
      Mean [Ca2+]i values as well as Oscillation Indices (which reflect the oscillatory
      behavior of cells) in singles and doublets and found that they were not different
      (P > 0.05). However, the phenotype of the adjoining cell had a profound influence
      on both of these calcium parameters, such that the presence of one mammotrope
      could consistently decrease (P < 0.05) the Mean [Ca2+]i value (39.17 +/- 3.83 vs.
      56.24 +/- 5.56 in M-nonM) and Oscillation Index (10.19 +/- 1.76 vs. 21.21 +/-
      3.73 in M-nonM) of its neighboring counterpart. A more detailed analysis of
      oscillatory patterns in these cells revealed that nonoscillators were more
      abundant in M-M (23%) than in M-nonM (12%) doublets. Taken together, our results
      indicate that PRL-secreting cells convey a signal that dampens the oscillatory
      behavior of neighboring mammotropes. Thus, it appears that it is the phenotype
      rather than the physical presence of a neighbor that controls intercellular
      regulation of calcium dynamics among mammotropes.

PMID- 9607811
TI  - Apoptosis in the pancreatic islet cells of the neonatal rat is associated with a
      reduced expression of insulin-like growth factor II that may act as a survival
      factor.
AB  - Islet cell ontogeny will define adult beta-cell mass and will consist of a
      balance of islet cell birth and death. We have investigated the ontogeny of
      factors that may be related to developmental apoptosis in the islets, insulin
      like growth factor II (IGF-II) and inducible nitric oxide synthase (iNOS), in
      pancreata of young Wistar rats. Pancreata were collected from rats of 21 days
      gestation to 29 days postnatal age. In situ hybridization and
      immunohistochemistry showed that IGF-II was expressed and present in fetal and
      neonatal islet cells, but declined rapidly 2 weeks after birth. Little IGF-I was
      associated with fetal or postnatal islets. Apoptosis in islet cells was
      visualized by molecular histochemistry for DNA breakage in tissue sections.
      Apoptosis was low in the fetus, but increased in incidence postnatally so that
      13% of islet cells were undergoing apoptosis on postnatal day 14, with the
      incidence declining thereafter. Immunohistochemistry for iNOS showed that it was
      expressed within beta-cells and was most abundant 12 days after birth. When
      islets were isolated from rat pancreata 20-22 days after birth, islet cell
      viability, DNA synthetic rate, and insulin release were reduced after incubation
      with interleukin-1beta, tumor necrosis factor, or interferon-gamma. An increased
      rate of islet cell survival was found after simultaneous incubation with IGF-I or
      -II. Cytokine-mediated islet cell death involved the induction of apoptosis.
      Islets isolated from neonatal rats were not killed after exposure to these
      cytokines at the same concentrations, but cytokine-induced cell death was seen
      when neonatal islets were incubated with a neutralizing antibody against IGF-II.
      These experiments show that a peak of islet cell apoptosis that is maximal in the
      rat pancreas 14 days after birth is temporally associated with a fall in the
      islet cell expression of IGF-II. IGF-II was shown to function as an islet
      survival factor in vitro. The induction of islet cell apoptosis in vivo may
      involve an increased expression of iNOS within beta-cells.

PMID- 9607812
TI  - Regional expression of transforming growth factor-alpha in rat ventral prostate
      during postnatal development, after androgen ablation, and after androgen
      replacement.
AB  - The prostate is a highly heterogeneous organ, composed of different types of
      epithelial and stromal cells organized regionally along the ductal network.
      Although androgen-stimulated growth and maintenance of the prostate gland
      primarily involve epithelial cells, it is unclear whether all epithelial cells
      are androgen dependent. Moreover, the actions of androgens may not be direct; a
      number of polypeptide growth factors, including transforming growth factor-alpha
      (TGFalpha), are postulated to mediate androgen action in the rat prostate. In
      this investigation, using an immunohistochemical technique, we examined the
      cellular and regional expression of TGFalpha in the rat ventral prostate during
      postnatal development to adulthood. TGFalpha-immunopositive cells were located
      throughout the ductal epithelium from postnatal days 5-20. By day 45 and
      thereafter, regional variation in TGFalpha expression became apparent; epithelial
      cells in the proximal segment exhibited intense staining, whereas those in the
      distal segment exhibited negligible staining. These observations were coincident
      with increased serum testosterone concentrations at puberty. To understand the
      role of androgen in the expression of TGFalpha in the epithelial cells of the
      distal and proximal segments of the adult rat ventral prostate, androgen was
      withdrawn by castration, and testosterone subsequently was administered. Androgen
      receptor protein expression decreased after castration and reappeared after
      androgen replacement in both the distal and proximal segments. TGFalpha staining
      was negligible in epithelial cells of the distal segment of intact adult rats,
      became prominent by 7 days after castration, but then diminished after the
      administration of testosterone. Western blot analyses revealed the presence of a
      specific 30-kDa immunoreactive form of TGFalpha in rat ventral prostate, and its
      quantity reflected the staining intensities observed in the immunohistochemical
      studies. These results suggest that TGFalpha expression is negatively regulated
      by androgen in epithelial cells of the distal segment. In contrast, staining for
      TGFalpha in epithelial cells of the proximal segment did not change with
      castration or testosterone administration, suggesting that TGFalpha is not
      regulated by androgen in this region of the ventral prostate. In summary,
      TGFalpha expression is differentially regulated among epithelial cells localized
      in two different regions of the ventral prostate. We hypothesize that TGFalpha
      may function as a survival factor for epithelial cells which, as a consequence of
      its expression, become androgen independent and thus escape apoptotic cell death
      after androgen ablation.

PMID- 9607813
TI  - Identification of thyroid transcription factor-1 in C cells and parathyroid
      cells.
AB  - We have identified thyroid transcription factor-1 (TTF-1) mRNA in parafollicular
      C cells of the adult rat thyroid and in parathyroid cells; in each case the
      signal is stronger than in the thyrocytes themselves. We additionally identify
      TTF-1 RNA in other adult rat tissues not previously recognized to contain TTF-1
      in developmental or knockout studies: basal layer cells of flattened squamous
      epithelium in skin and esophagus, three layers of the retina, i.e. pigmented
      epithelium, inner granular layer, and ganglion cell layer, and three areas of the
      brain, i.e. anterior pituitary, cerebellum, and hippocampus. Based on the array
      of cells that are shown to contain TTF-1 in this report, we speculate that TTF-1
      may have a role in the regulation of genes important in calcium homeostasis in
      the intact organism as well as different tissues.

PMID- 9607814
TI  - Neuropeptide Y lowers blood glucose in anaesthetized rats via a Y5 receptor
      subtype.
AB  - We have investigated the receptor subtype mediating effects of neuropeptide Y
      (NPY) on blood glucose concentrations. In anaesthetized rats a 120 min i.v.
      infusion of 2 microg/kg/min NPY lowered blood glucose by 26 mg/dl. This was
      mimicked by the same dose of peptide YY (PYY), NPY2-36, PYY3-36 and
      [Leu31,Pro34]NPY but not by NPY13-36, PYY13-36 or rat or human pancreatic
      polypeptide. The effects of NPY and [Leu31,Pro34]NPY were not inhibited by 10
      microg/kg/min BIBP 3226. Neither treatment significantly altered plasma insulin
      concentrations. We conclude that NPY lowers blood glucose concentrations via a Y5
      receptor subtype, i.e. a subtype which has also been implicated in stimulation of
      food intake.

PMID- 9607815
TI  - Mice lacking the type I interleukin-1 receptor do not lose bone mass after
      ovariectomy.
AB  - We measured the effects of ovariectomy on the bone mass of mice that lacked type
      I interleukin-1 receptor (IL-I R1 -/- mice) in two genetic backgrounds (C57BL/6 x
      129/Sv and C57BL/6) to investigate the role of interleukin-1 in the actions of
      estrogen on bone. At three weeks after surgery, ovariectomized wild-type mice
      decreased trabecular bone volume in the proximal humerus by 70% in a C57BL/6 x
      129/Sv background and 48% in a C57BL/6 background compared to sham-operated
      controls. In contrast, there was no significant decrease in trabecular bone mass
      in IL-1 R1 -/- mice after ovariectomy. The estrogen status of all groups was
      confirmed by measurement of uterine wet weight. These results demonstrate that a
      functional IL-1 response pathway is required for mice to lose trabecular bone
      mass after ovariectomy in this model and they imply that IL-1 is an important
      mediator of the effects of ovariectomy on bone mass. Hence, therapeutic
      interventions that block the effects of IL-1 on bone may be beneficial for
      treating diseases of rapid bone loss such as post-menopausal osteoporosis.

PMID- 9607817
TI  - Characterization of mouse retinoid X receptor (RXR)-beta gene promoter: negative
      regulation by tumor necrosis factor (TNF)-alpha.
AB  - A genomic clone of mouse retinoid X receptor (RXR)-beta (Rxrb) has recently been
      isolated and mapped within the H2-K region of the mouse major histocompatibility
      complex. A putative 250-bp promoter, which is located between Rxrb and H2-Ke4,
      and may possibly be their common promoter, has also been identified. In order to
      study the gene regulation of Rxrb, we analyzed the transcriptional function of
      the Rxrb promoter with chimeric constructs containing the Rxrb promoter fragments
      fused upstream of a firefly luciferase cDNA, which were transiently transfected
      into rat GH3 cells. We found that 1) a part of the H2-Ke4 genomic region (1.9
      kb), as well as the 250-bp promoter, was transcriptionally active as an Rxrb
      promoter; 2) tumor necrosis factor (TNF)-alpha significantly repressed the
      activity of the 250-bp promoter although thyroid hormone, 9-cis retinoic acid,
      interleukin (IL)-1beta, and IL-6 did not affect the activity; 3) either the
      change in orientation or point mutations of a consensus NF-kappaB site located in
      the 250-bp promoter did not affect the repression; 4) SB 203580, a highly
      specific inhibitor of p38 mitogen-activated protein (MAP) kinase, completely
      abolished the repression by TNF-alpha. These data suggest that TNF-alpha
      represses the promoter activity of the 250-bp region, and the repression is
      mediated by p38 MAP kinase independent of NF-kappaB. We thus have first shown a
      relation between the retinoic acid receptor and a cytokine TNF-alpha.

PMID- 9607816
TI  - 25-Hydroxycholesterol is not a ligand for the orphan nuclear receptor
      steroidogenic factor-1 (SF-1).
AB  - The orphan nuclear receptor steroidogenic factor-1 (SF-1) is involved in the
      transcriptional regulation of all the steroid hydroxylase genes, and also
      regulates the transcription of the genes for Mullerian Inhibitory substance
      (MIS), alpha subunit of glycoprotein hormone, LHbeta, oxytocin, GnRH receptor,
      ACTH receptor, prolactin receptor, DAX-1, and steroidogenic acute regulatory
      protein. Other members of the nuclear receptor gene family, including steroid
      hormone, thyroid hormone, retinoic acid, PPAR, and vitamin D receptors must bind
      ligand to activate transcription, but SF-1 has been considered to be an orphan
      nuclear receptor because, when identified, it had no known ligand. A recent
      publication suggested that transcriptional regulation by SF-1, expressed in a non
      steroidogenic CV-1 cells, could be activated by oxysterols suggesting that these
      compounds could serve as natural ligands for SF-1. We now demonstrate that 25
      hydroxycholesterol, either added exogenously or synthesized endogenously in
      steroidogenic mouse Leydig MA-10 cells, did not act as a ligand for SF-1, as it
      did not increase transcription from six different SF-1-dependent DNA sequences.
      Furthermore, the abundance of these oxysterols in MA-10 cells was much less than
      concentrations needed for activation of SF-1 in CV-1 cells, indicating that SF-1
      is not constitutively bound by ligand in MA-10 cells. Thus, in steroidogenic
      cells, transcriptional regulation of the steroid hydroxylase genes by SF-1 does
      not depend upon the presence of 25-hydroxycholesterol, and is not modified by its
      presence.

PMID- 9607818
TI  - Dynamin associates with Src-Homology Collagen (Shc) and becomes tyrosine
      phosphorylated in response to insulin.
AB  - The activated insulin receptor phosphorylates docking proteins such as Src
      Homology Collagen (Shc) and Insulin Receptor Substrate-1 (IRS-1), which then bind
      several proteins that contain a Src-Homology 2 (SH2) domain. Both Shc and IRS-1
      associate with Growth Factor Receptor-Bound protein 2 (Grb2), an adaptor
      molecule. The hormone-receptor complex is then rapidly internalized through
      coated-pits. Dynamin, a 100 kDa protein with GTPase activity, is thought to play
      a crucial role in receptor-mediated endocytosis. In this study, we show that
      insulin induces tyrosine phosphorylation of dynamin in cells overexpressing human
      insulin receptors. Phosphorylation is observed rapidly, i.e. within 1 minute of
      insulin treatment. Moreover, exposure of cells to the hormone leads to co
      immunoprecipitation of dynamin with Shc and with insulin receptor. Since dynamin
      constitutively associates with Grb2, it could be recruited to the insulin
      signaling complex through binding of Grb2 to tyrosine-phosphorylated Shc.

PMID- 9607819
TI  - Induction of mucosal immunity against herpes simplex virus type 1 in the mouse
      protects against ocular infection and establishment of latency.
AB  - Immune responses were assessed after intranasal immunization of mice with a
      mixture of herpes simplex virus type 1 (HSV-1) glycoproteins with cholera toxin
      and its B subunit as adjuvant. Antigen-specific serum antibodies, which were
      largely IgG with IgG1 the major subclass, neutralized virus in vitro with a titer
      equivalent to that elicited by active infection. Significant levels of antigen
      specific IgA were found in mucosal fluids of the eye as well as the vagina.
      Lymphocytes from draining lymph nodes showed secondary proliferative responses
      when cultured with HSV-1 in vitro, in immunized mice only, with the production of
      interleukin-2, interferon-gamma, interleukin-4, and interleukin-5. After ocular
      challenge, immunized mice were protected against the development of severe eye
      disease, zosteriform spread, or encephalitis, whereas the incidence of clinical
      symptoms in mock-immunized mice was 83%, 74%, and 52%, respectively. Finally, the
      incidence of latency was reduced from 88% to 13% after intranasal immunization.

PMID- 9607820
TI  - Recombinant human eosinophil-derived neurotoxin/RNase 2 functions as an effective
      antiviral agent against respiratory syncytial virus.
AB  - A dose-dependent decrease in infectivity was observed on introduction of
      eosinophils into suspensions of respiratory syncytial virus group B (RSV-B). This
      antiviral effect was reversed by ribonuclease inhibitor, suggesting a role for
      the eosinophil secretory ribonucleases. Recombinant eosinophil-derived neurotoxin
      (rhEDN), the major eosinophil ribonuclease, promoted a dose-dependent decrease in
      RSV-B infectivity, with a 40-fold reduction observed in response to 50 nM rhEDN.
      Ribonucleolytically inactivated rhEDN (rhEDNdK38) had no antiviral activity.
      Semiquantitative reverse transcriptase-polymerase chain reaction demonstrated
      loss of viral genomic RNA in response to rhEDN, suggesting that this protein
      promotes the direct ribonucleolytic destruction of extracellular virions.
      Ribonuclease A had no antiviral activity even at approximately 1000-fold higher
      concentrations, suggesting that rhEDN has unique features other than ribonuclease
      activity that are crucial to its effectiveness. These results suggest that rhEDN
      may have potential as a therapeutic agent for prevention or treatment of disease
      caused by RSV.

PMID- 9607821
TI  - Cytomegalovirus-infected endothelial cells recruit neutrophils by the secretion
      of C-X-C chemokines and transmit virus by direct neutrophil-endothelial cell
      contact and during neutrophil transendothelial migration.
AB  - Infection of endothelial cells with an endothelial cell-tropic clinical isolate
      of cytomegalovirus (CMV), C1FE, induced enhanced production of the neutrophil
      chemoattractant C-X-C chemokines interleukin-8 and GROalpha. Infected endothelial
      cell supernatants induced neutrophil chemotaxis in a transendothelial migration
      assay. Neutrophils acquired the CMV structural protein pp65 following either
      coculture with infected endothelial cells or transmigration through infected
      endothelium. The lack of CMV p72 expression in the neutrophils indicated that
      viral replication had not occurred in these cells. Of importance, neutrophils
      acquired infectious CMV during transmigration across infected endothelium and
      were subsequently able to transmit infectious virus to fibroblasts. Thus, CMV
      infected endothelial cells can recruit neutrophils by the secretion of C-X-C
      chemokines and can transmit the virus to them by direct cell-to-cell contact and
      during neutrophil transendothelial migration, suggesting that the neutrophil
      endothelial cell interaction plays an important role in virus dissemination in
      vivo.

PMID- 9607822
TI  - Dynamics of hepatitis C viremia following interferon-alpha administration.
AB  - Knowledge of the dynamics of hepatitis C virus (HCV) in vivo is important for
      elucidation of its pathogenesis and the establishment of therapeutic guidelines.
      The aim of this study was to obtain kinetic information about virus load
      following interferon-alpha (IFN-alpha) administration. Serial serum HCV core
      protein and HCV RNA levels were measured. IFN-alpha exponentially reduced serum
      HCV levels. The mean (+/-SD) viral half-life was 7.0 +/- 2.6 h in HCV core
      protein assay and 7.2 +/- 3.1 h in HCV RNA assay on the first day of therapy.
      This initial rapid decrease was followed by a slower decrease in serum HCV levels
      thereafter. Thus, the biphasic reduction in virus load during IFN-alpha therapy
      was demonstrated.

PMID- 9607823
TI  - Perinatal transmission of hepatitis C virus from human immunodeficiency virus
      type 1-infected mothers. Women and Infants Transmission Study.
AB  - Antepartum plasma hepatitis C virus (HCV) RNA was quantified in 155 mothers
      coinfected with HCV and human immunodeficiency virus type 1 (HIV-1), and HCV RNA
      was serially assessed in their infants. Of 155 singleton infants born to HCV
      antibody-positive mothers, 13 (8.4%) were HCV infected. The risk of HCV infection
      was 3.2-fold greater in HIV-1-infected infants compared with HIV-1-uninfected
      infants (17.1% of 41 vs. 5.4% of 112, P = .04). The median concentration of
      plasma HCV RNA was higher among the 13 mothers with HCV-infected infants (2.0 x
      10(6) copies/mL) than among the 142 mothers with HCV-negative infants (3.5 x
      10(5) copies/mL; P < .001), and there were no instances of HCV transmission from
      40 mothers with HCV RNA concentrations of < 10(5) copies/mL. Women dually
      infected with HIV-1 and HCV but with little or no detectable HCV RNA should be
      reassured that the risk of perinatal transmission of HCV is exceedingly low.

PMID- 9607824
TI  - Down-regulation of interleukin-10 expression and production is associated with
      spontaneous proliferation by lymphocytes from human T lymphotropic virus type II
      infected persons.
AB  - Cytokines from peripheral blood mononuclear cells (PBMC) from human T
      lymphotropic virus (HTLV)-II-infected persons were studied to delineate the
      mechanism(s) of spontaneous lymphocyte proliferation (SLP). Culturing HTLV-II
      infected PBMC that spontaneously proliferate (SLP+) resulted in greater mRNA
      expression and production of interferon-gamma, interleukin (IL)-4, and IL-5, with
      a concomitant decrease in IL-10, than was seen with nonproliferating (SLP ) and
      normal PBMC. While IL-2 mRNA expression was higher, production was lower in SLP+
      PBMC than in SLP and normal PBMC, implying that the proliferating cells are
      utilizing IL-2. Neutralization of IL-2 resulted in partial inhibition, suggesting
      that other cytokines also affect SLP. Addition of recombinant IL-10 inhibited the
      proliferation of SLP+ PBMC. Further, blocking costimulatory signals with
      monoclonal antibodies against CD80/CD86 resulted in increased IL-10 production
      with concomitant inhibition of SLP. The mechanism(s) underlying HTLV-II
      associated SLP in vitro involve increased utilization of IL-2 and down-regulation
      of IL-10.

PMID- 9607825
TI  - Virus burden in lymph nodes and blood of subjects with primary human
      immunodeficiency virus type 1 infection on bitherapy.
AB  - At present, it is not known whether undetectable plasma viremia corresponds to an
      absence of human immunodeficiency virus type 1 (HIV-1) replication in lymphoid
      tissues. This issue has been explored in 11 subjects with primary HIV-1 infection
      treated with zidovudine plus didanosine by evaluating virologic markers in blood
      and lymphoid tissues 9-18 months after initiation of treatment. These markers
      include plasma viremia, measured with a sensitive assay with a detection limit of
      20 HIV-1 RNA copies/mL, infectious virus titers and proviral DNA in lymph node
      mononuclear cells, and HIV-1 RNA in lymphoid tissue. Five subjects had plasma
      viremia <20 copies/mL and showed no evidence of viral replication in lymphoid
      tissue. Six subjects had both detectable plasma viremia and evidence of HIV-1 RNA
      in lymphoid tissue. The results indicate that absence of detectable HIV RNA in
      lymphoid tissue is associated with viremia levels of HIV-1 RNA <20 copies/mL.

PMID- 9607826
TI  - JC virus remains latent in peripheral blood B lymphocytes but replicates actively
      in urine from AIDS patients.
AB  - JC virus (JCV) is thought to reach the central nervous system by a vascular
      route. To determine whether JCV is conveyed in peripheral blood as latent or
      reactivated virus, blood leukocytes, plasma, and urine from 50 AIDS patients and
      plasma and B lymphocytes from 60 AIDS patients were investigated. Peripheral
      blood from 88 human immunodeficiency virus-negative blood donors was studied.
      Nested polymerase chain reaction assays allowed the identification of JCV T DNA
      and VP1 mRNAs. The latter indicate viral replication. Blood harbored JCV DNA in
      31.8% of AIDS patients (only 2.3% of blood donors; P > .001) and urine in 56%.
      VP1 mRNAs were detected in blood of 1 AIDS patient. Notably, 38% of DNA-positive
      urine samples and 10 cerebrospinal fluid samples (CSF) from AIDS patients with
      progressive multifocal leukoencephalopathy contained JCV mRNAs. Thus, JCV was
      significantly more frequent in blood from AIDS patients than from controls, but,
      in most instances, it was latent, whereas active replication was detected in
      urine and CSF.

PMID- 9607827
TI  - Emergence of multi-dideoxynucleoside-resistant human immunodeficiency virus type
      1 variants, viral sequence variation, and disease progression in patients
      receiving antiretroviral chemotherapy.
AB  - A set of five reverse transcriptase mutations, which include Q151M, is known to
      confer multi-dideoxynucleoside resistance (MDR) in human immunodeficiency virus
      type 1 (HIV-1). MDR mutations were found in 6 (17%) HIV-1 isolates from 36
      patients, most of whom were receiving long-term combination therapy. Q151M was
      among the first of the substitutions to appear. Additional substitutions were
      observed, although none were common among all 6 patients. Certain zidovudine
      related mutations were not observed together with the MDR mutations, indicating
      possible enzymatic constraint. During chemotherapy, the HIV-1 RNA levels in the 6
      patients initially decreased and then rose. Initially, CD4 cell counts also
      responded favorably but were near or below baseline beyond 40 months of therapy.
      Such loss of clinical benefits appeared to coincide with the appearance of the
      MDR mutations. A common background genotype was not observed among HIV-1 isolates
      with or without MDR.

PMID- 9607828
TI  - A pilot study of nevirapine, indinavir, and lamivudine among patients with
      advanced human immunodeficiency virus disease who have had failure of combination
      nucleoside therapy.
AB  - The effects of nevirapine, indinavir, and lamivudine in combination were studied
      among 22 human immunodeficiency virus (HIV)-infected patients with CD4 cell
      counts < or =50/mm3, whose options for antiretroviral therapy were limited by
      clinical or laboratory failure or toxicity with previous regimens. Median plasma
      HIV RNA was 5.16 log10 copies/mL at baseline, decreasing by a median of 3.12
      log10 copies/mL at 24 weeks. Median baseline CD4 cell count was 30/mm3,
      increasing by a median of 95/mm3 at week 24. Adverse reactions led to drug
      discontinuation in 4 cases. Steady-state pharmacokinetic analysis in 17 patients
      was consistent with an interaction between nevirapine and indinavir. Nevirapine
      plasma levels were within the expected range, while indinavir levels were lower
      than expected. Despite this interaction, the combination of nevirapine,
      indinavir, and lamivudine was safe and well-tolerated and had substantial
      antiviral and immunologic effects lasting for the 24-week study.

PMID- 9607829
TI  - Dual resistance to zidovudine and lamivudine in patients treated with zidovudine
      lamivudine combination therapy: association with therapy failure.
AB  - Human immunodeficiency virus type 1 (HIV-1) strains dually resistant to
      zidovudine and lamivudine (3TC) may arise during zidovudine-3TC combination
      therapy. The objective of this cross-sectional study (n = 43 patients) was to
      test the association between therapy response (clinical and immunologic) to
      zidovudine-3TC and the level of phenotypic zidovudine resistance and zidovudine
      resistance-associated genotype of 3TC-resistant isolates. Other variables
      included were baseline CD4+ cell count, baseline Centers for Disease Control and
      Prevention (CDC) classification, virus load, and time receiving zidovudine.
      Phenotypic resistance was assessed using a recombinant virus assay. Genotypic
      analysis was based on population sequencing of plasma HIV-1. In a univariate
      analysis using a logistic regression model, it was found that therapy response
      was significantly associated with phenotypic and genotypic zidovudine resistance,
      baseline CD4+ cell count, and virus load. After adjustment for all variables,
      phenotypic resistance to zidovudine remained the only significantly associated
      factor, independent of baseline CD4+ cell count, baseline CDC classification, and
      virus load.

PMID- 9607830
TI  - A preliminary evaluation of nelfinavir mesylate, an inhibitor of human
      immunodeficiency virus (HIV)-1 protease, to treat HIV infection.
AB  - A phase I/II dose-ranging open-label 28-day monotherapy study of the safety,
      pharmacokinetics, and antiviral activity of nelfinavir mesylate (Viracept), an
      inhibitor of human immunodeficiency virus (HIV)-1 protease, was done in 65 HIV-1
      infected subjects. After 28 days, 54 responding subjects entered an open-label
      extension that allowed for the addition of nucleoside inhibitors of reverse
      transcriptase and dose escalation to maintain durability. The drug was well
      tolerated and demonstrated robust antiviral activity, with demonstrable
      superiority of the 750 mg and 1000 mg three times daily regimens. Thirty subjects
      who continued to receive therapy at 12 months attained a persistent 1.6 log10
      reduction in HIV RNA, accompanied by a mean increase in CD4 cells of 180-200/mm3.
      Studies of viral genotype and phenotype after virus rebound revealed that the
      initial active site mutation allowing for nelfinavir resistance is mediated by a
      unique amino acid substitution in the HIV-1 protease D30N, which does not confer
      in vitro phenotypic cross-resistance to the currently available protease
      inhibitors.

PMID- 9607831
TI  - The risk of disease progression is determined during the first year of human
      immunodeficiency virus type 1 infection.
AB  - A cohort of 103 human immunodeficiency virus type 1 (HIV-1)-infected persons with
      well-defined dates of seroconversion were studied to determine whether baseline
      plasma HIV RNA loads 6-12 months after seroconversion have prognostic value.
      Baseline plasma virus loads had predictive value for the disease-free survival
      rate and for the survival rate. The level of baseline HIV RNA also had a strong
      negative predictive value for the CD4+ T cell count during the fifth year of
      infection: A baseline load >5 log was predictive of a CD4+ T cell count <500/mm3
      5 years after infection. Baseline HIV RNA load was a CD4+ T cell-independent
      predictor of progression to death. The major finding was that the disease outcome
      for HIV-1-infected persons is already determined during the first year of
      infection.

PMID- 9607832
TI  - CCR5/delta(ccr5) heterozygosity: a selective pressure for the syncytium-inducing
      human immunodeficiency virus type 1 phenotype. NIAID AIDS Clinical Trials Group
      Protocol 241 Virology Team.
AB  - Mechanisms underlying the delay in dominance of syncytium-inducing (SI) phenotype
      HIV-1 (human immunodeficiency virus type 1) in vivo are unknown. Both random
      mutational events and selective pressures operative only late in the disease
      process have been suggested to underlie the shift from CCR5 to alternative
      coreceptor usage. Among the moderately advanced patients who entered AIDS
      Clinical Trials Group protocol 241, SI viral phenotype was more common among
      CCRS/delta(ccr5) heterozygotes (7/7, 100%) than among CCR5/CCR5 homozygotes
      (29/88, 33%; P < .001, Fisher's exact test). Other characteristics did not differ
      at study entry by CCR5 genotype, including median CD4 cell counts, plasma RNA
      levels, and infectious HIV-1 titers in circulating cells. These data indicate
      that CCR5/delta(ccr5) heterozygosity, which decreases cell-surface levels of CCR5
      available to serve as an HIV-1 entry coreceptor, is a selective pressure for
      evolution of T cell line-tropic viruses that use an alternative coreceptor.

PMID- 9607833
TI  - Human immunodeficiency virus infection alters antigen-induced cytokine responses
      in patients with active mycobacterial diseases.
AB  - Peripheral blood cells from 29 patients with active Mycobacterium avium (MAC) or
      Mycobacterium tuberculosis diseases were tested for mycobacterial antigen-induced
      interferon (IFN)-gamma and interleukin (IL)-4 production. Among MAC patients,
      human immunodeficiency virus (HIV) infection was associated with an 80% decrease
      in those who produced IFN-gamma, resulting in a predominantly type 2 cytokine
      profile. HIV infection in patients with tuberculosis correlates with a 37%
      increase in those producing IL-4 and a type 1 to type 0 profile shift. These
      qualitative changes were independent of CD4+ or CD8+ cell numbers. The amounts of
      both IFN-gamma and IL-4 were decreased in the HIV-infected population.
      Quantitative reduction of IFN-gamma was the result of fewer secreting cells
      rather than a down-regulation at the single-cell level. Disseminated disease was
      restricted to 2 of 5 HIV-infected MAC patients with a type 2 cytokine profile and
      4 of 5 HIV-infected tuberculosis patients with a type 0 profile. These results
      demonstrated a shift in mycobacterial antigen-specific cytokine profiles from
      type 1 to type 0 and to type 2, in parallel with AIDS progression.

PMID- 9607834
TI  - A combination of thalidomide plus antibiotics protects rabbits from mycobacterial
      meningitis-associated death.
AB  - Tuberculous meningitis (TBM) is a devastating form of tuberculosis that occurs
      predominantly in children and in immunocompromised adults. To study the
      pathogenesis of TBM, a rabbit model of acute mycobacterial central nervous system
      infection was set up (8-day study). Inoculation of live Mycobacterium bovis
      Ravenel intracisternally induced leukocytosis (predominantly mononuclear cells),
      high protein levels, and release of tumor necrosis factor-alpha (TNF-alpha) into
      the cerebrospinal fluid within 1 day. Histologically, severe meningitis with
      thickening of the leptomeninges, prominent vasculitis, and encephalitis was
      apparent, and mortality was 75% by day 8. In animals treated with antituberculous
      antibiotics only, the inflammation and lesions of the brain persisted despite a
      decrease in mycobacteria; 50% of the rabbits died. When thalidomide treatment was
      combined with antibiotics, there was a marked reduction in TNF-alpha levels,
      leukocytosis, and brain pathology. With this combination treatment, 100% of the
      infected rabbits survived, suggesting a potential clinical use for thalidomide in
      TBM.

PMID- 9607835
TI  - A single 16S ribosomal RNA substitution is responsible for resistance to amikacin
      and other 2-deoxystreptamine aminoglycosides in Mycobacterium abscessus and
      Mycobacterium chelonae.
AB  - Twenty-six clinical isolates of Mycobacterium abscessus resistant to amikacin
      were identified. Most isolates were from patients with posttympanostomy tube
      placement otitis media or patients with cystic fibrosis who had received
      aminoglycoside therapy. Isolates were highly resistant (MICs > 1024 microg/mL) to
      amikacin, kanamycin, gentamicin, tobramycin, and neomycin (all 2-deoxystreptamine
      aminoglycosides) but not to streptomycin. Sequencing of their 16S ribosomal (r)
      RNA revealed that 16 (94%) of 17 had an A-->G mutation at position 1408. In vitro
      selected amikacin-resistant mutants of M. abscessus and Mycobacterium chelonae
      had the same resistance phenotype, and 15 mutants all had the same A-->G
      substitution at position 1408. Introducing an rRNA operon from Mycobacterium
      smegmatis with a mutated A-->G at this position into a single functional allelic
      rRNA mutant of M. smegmatis produced the same aminoglycoside resistance
      phenotype. These studies demonstrate this 16S rRNA mutation is responsible for
      amikacin resistance in M. abscessus, which has only one copy of the rRNA operon.

PMID- 9607837
TI  - An outbreak of Escherichia coli O157:H7 infections associated with leaf lettuce
      consumption.
AB  - In July 1995, 40 Montana residents were identified with laboratory-confirmed
      Escherichia coli O157:H7 infection; 52 residents had bloody diarrhea without
      laboratory confirmation. The median age of those with laboratory-confirmed cases
      was 42 years (range, 4- 86); 58% were female. Thirteen patients were
      hospitalized, and 1 developed hemolytic-uremic syndrome. A case-control study
      showed that 19 (70%) of 27 patients but only 8 (17%) of 46 controls reported
      eating purchased (not home-grown) leaf lettuce before illness (matched odds
      ratio, 25.3; 95% confidence interval, 3.9-1065.6). Pulsed-field gel
      electrophoresis identified a common strain among 22 of 23 isolates tested.
      Implicated lettuce was traced to two sources: a local Montana farm and six farms
      in Washington State that shipped under the same label. This outbreak highlights
      the increasing importance of fresh produce as a vehicle in foodborne illness.
      Sanitary growing and handling procedures are necessary to prevent these
      infections.

PMID- 9607836
TI  - Tumor necrosis factor-alpha, interleukin-6, and interleukin-8 secretion and the
      acute-phase response in patients with bacterial and tuberculous osteomyelitis.
AB  - Osteomyelitis, or bone infection, is a major worldwide cause of morbidity.
      Treatment is frequently unsatisfactory, yet little is known about pathogenesis of
      infection. Plasma tumor necrosis factor (TNF), interleukin (IL)-6, and IL-8
      concentrations were measured before and after lipopolysaccharide stimulation of
      whole blood from patients with bacterial and tuberculous osteomyelitis and from
      controls. Patients with bacterial and tuberculous osteomyelitis mounted an acute
      phase response and were anemic and febrile. However, plasma IL-6 concentrations
      were significantly elevated in only tuberculous osteomyelitis patients (vs.
      controls, P < .05). IL-6 concentrations correlated with erythrocyte sedimentation
      rate, C-reactive protein level, and plasma albumin concentration, all acute-phase
      markers. There were no other correlations between cytokine concentrations and
      clinical data. Following ex vivo stimulation, TNF, IL-6, and IL-8 were secreted
      equally by patients and controls. In summary, tuberculous osteomyelitis is
      characterized by elevated systemic IL-6 concentrations associated with an acute
      phase response. For further insight into immunopathology of osteomyelitis,
      studies on infected bone are required.

PMID- 9607838
TI  - Enteric infections in an endemic area induce a circulating antibody-secreting
      cell response with homing potentials to both mucosal and systemic tissues.
AB  - Enteric infections induce a response of circulating pathogen-specific antibody
      secreting cells (ASC). The expression of homing receptors (HRs) on these cells
      was studied in patients with diarrhea caused by Vibrio cholerae in Bangladesh, an
      area in which cholera is endemic. The gut HR, alpha4beta7, was expressed by
      approximately 80% of the ASC, indicating mucosal homing of these cells. However,
      the peripheral lymph node HR, L-selectin, was also expressed by approximately 80%
      of the ASC specific to either cholera toxin or O antigen. In earlier findings
      after oral immunization in nonendemic areas, alpha4beta7 has been expressed by
      approximately 100% and L-selectin by approximately 50% of the ASC. In comparison,
      the present data speak for a more systemic targeting of the immune response
      associated with long-lasting immunity in an endemic area. The results thus
      provide insight for the continued development and evaluation of vaccines.

PMID- 9607839
TI  - Invasion and survival of Streptococcus pyogenes in eukaryotic cells correlates
      with the source of the clinical isolates.
AB  - The invasiveness of 96 group A streptococci (GAS) isolates (56 from throat or
      skin and 40 from blood) were analyzed. GAS invasion strongly correlated with the
      source of the isolates, whereas no correlation was observed with the Vir type.
      Isolates from throat or skin exhibited the highest invasion efficiency (57% were
      between 0.1% and 10%). In contrast, 77.5% of the blood isolates were noninvasive
      (efficiency <0.01%) and only 7.5% exhibited rates comparable to those of throat
      or skin isolates (>0.1%). Immunofluorescence studies of 34 selected isolates
      showed that attachment and invasion are strain-related. Although isolates with
      high invasiveness usually exhibit high attachment, isolates that showed high
      attachment and no invasion or poor attachment and efficient internalization were
      identified. The ability of GAS to invade and survive within eukaryotic cells may
      provide bacteria a sure niche, in which they are protected against host defense
      mechanisms or antimicrobial agents favoring their local persistence.

PMID- 9607840
TI  - Prevention of experimental Haemophilus ducreyi infection: a randomized,
      controlled clinical trial.
AB  - Human subjects were infected with Haemophilus ducreyi. All subjects developed
      papules and were randomized to treatment with a single dose of azithromycin (1 g)
      or ciprofloxacin (500 mg). At weekly intervals, volunteers were reinoculated with
      H. ducreyi, and drug concentrations were measured in peripheral blood mononuclear
      cells (PBMC). When papules developed, the subjects were treated with antibiotics
      and dismissed from the study. Eight of the ciprofloxacin-treated subjects
      developed papules 1 week after the initial treatment, and the ninth subject
      developed disease 2 weeks after treatment. The 9 azithromycin-treated subjects
      developed papules 4-10 weeks (mean, 6.8) after the initial treatment (P < .001).
      Azithromycin was detected in PBMC for 3-6 weeks (mean, 4). Pre- and posttreatment
      lesions had histology typical of experimental chancroid or were culture positive.
      Azithromycin prevents experimental chancroid for nearly 2 months. These findings
      have implications for strategies to prevent chancroid.

PMID- 9607841
TI  - Avidity of IgG for Streptococcus pneumoniae type 6B and 23F polysaccharides in
      infants primed with pneumococcal conjugates and boosted with polysaccharide or
      conjugate vaccines.
AB  - Relative avidity of IgG to Streptococcus pneumoniae type 6B and 23F
      polysaccharides (PSs) was measured in sera of children immunized with
      pneumococcal vaccines, using an EIA and the chaotropic agent thiocyanate. Infants
      were immunized at 2, 4, and 6 months of age with pneumococcal PS-diphtheria
      toxoid conjugate vaccine, and boosted at 14 months with the homologous conjugate
      or a pneumococcal PS vaccine. The concentrations of antibodies to 6B and 23F PSs
      increased significantly after the booster with both vaccines. A significant
      increase in the avidity of anti-6B and anti-23F antibodies was seen after the
      booster with conjugate but not with PS vaccine. Avidity also increased in another
      group of infants primed and boosted with pneumococcal PS-meningococcal protein
      conjugate but not in a group boosted with PS vaccine after priming with
      pneumococcal PS-tetanus toxoid conjugate. In the latter group, however, the
      avidity of anti-6B was high before boosting.

PMID- 9607842
TI  - Both C3a and C3a(desArg) regulate interleukin-6 synthesis in human peripheral
      blood mononuclear cells.
AB  - Synthesis of complement components is part of the acute-phase response.
      Interleukin-6 (IL-6) is a critical mediator of the acute-phase response during
      infections and injuries. Plasma levels of C3a and IL-6 have been proposed as
      prognostic indicators in sepsis and trauma. The effects of C3a and C3a(des)Arg on
      IL-6 gene expression and protein production in human peripheral blood mononuclear
      cells (PBMC) were investigated. Neither C3a nor C3a(des)Arg alone induced
      detectable IL-6 protein or mRNA levels. However, C3a and C3a(des)Arg affected
      endotoxin-induced IL-6 synthesis in a dose-dependent manner. In nonadherent PBMC,
      C3a or C3a(des)Arg suppressed, while in adherent PBMC, C3a or C3a(des)Arg
      enhanced IL-6 protein and mRNA levels. These results suggest that C3a and
      C3a(des)Arg may provide a control mechanism of acute-phase responses by enhancing
      IL-6 synthesis in adherent monocytes at local inflammatory sites and by
      inhibiting IL-6 synthesis in circulating monocytes.

PMID- 9607843
TI  - Endothelial and epithelial cells do not respond to complexes of peptidoglycan
      with soluble CD14 but are activated indirectly by peptidoglycan-induced tumor
      necrosis factor-alpha and interleukin-1 from monocytes.
AB  - Peptidoglycan (PGN) activates macrophages through membrane CD14 (an endotoxin
      receptor) and binds to both soluble and membrane CD14. Since soluble CD14
      lipopolysaccharide (LPS) complexes activate CD14-negative endothelial and
      epithelial cells, this study tested whether soluble CD14-PGN complexes activate
      human umbilical vein endothelial cells and epithelial-like U373 cells to secrete
      interleukin (IL)-6, express vascular cellular adhesion molecule-1, and
      translocate nuclear factor-kappaB. In contrast to LPS, endothelial, epithelial,
      and other cells of non-hemopoietic origin were unresponsive to PGN through
      soluble or membrane-bound CD14, whereas cells of hemopoietic origin were
      responsive to both PGN and LPS. PGN, similarly to LPS, activated endothelial and
      epithelial cells indirectly in the presence of 2%-4% blood, by inducing secretion
      of both tumor necrosis factor-alpha and IL-1 from monocytes. These results reveal
      different mechanisms of CD14 function and cell activation for LPS and PGN and
      also demonstrate strong indirect activation of endothelial and epithelial cells
      by both PGN and LPS.

PMID- 9607844
TI  - Effect of antibody to capsular polysaccharide on eosinophilic pneumonia in murine
      infection with Cryptococcus neoformans.
AB  - The effect of the murine IgG1 monoclonal antibody (MAb) 2H1, which binds to
      Cryptococcus neoformans glucuronoxylomannan (GXM), on pulmonary infection in
      immunocompetent C57Bl/6 mice was examined. C57Bl/6 mice develop eosinophilic
      pneumonia in response to pulmonary cryptococcal infection. Survival, organ fungus
      burden, serum anticapsular antibody levels, and histopathology by light and
      electron microscopy were studied. MAb administration prior to infection prolonged
      survival without reducing the number of yeast in the lung or extrapulmonary
      sites. Compared with uninfected mice, occasional control and MAb-treated mice
      produced more IgM antibody to GXM or low levels of GXM-binding IgG1, IgG2b, or
      IgG3 antibodies. MAb-treated mice had fewer granules per eosinophil, indicating
      alteration in eosinophil physiology or degranulation (or both). Our results
      provide additional evidence that antibody administration can produce quantitative
      and qualitative changes in the inflammatory response to a pathogen.

PMID- 9607845
TI  - Effect of immune mechanisms on the pharmacokinetics and organ distribution of
      cryptococcal polysaccharide.
AB  - Cryptococcus neoformans is an encapsulated opportunistic fungus that can cause
      chronic infections accompanied by high tissue levels of capsular polysaccharide
      (CPS). CPS or its major component, glucuronoxylomannan (GXM), was administered to
      mice, and whole-body and tissue levels were measured. The role of monoclonal
      antibody (MAb), complement, and CD4 T cells in GXM clearance was also examined.
      These studies demonstrate that CPS is cleared from the blood within days but is
      retained in the body for weeks; that MAbs of all isotypes examined promote GXM
      clearance; that MAb-mediated GXM deposition in liver, but not in spleen, is Fc
      dependent; that complement enhances IgM-mediated GXM sequestration in liver but
      not spleen; and that CD4 T cells are not necessary for serum GXM clearance. The
      results have important implications for the eventual use of MAbs in treatment of
      cryptococcosis.

PMID- 9607846
TI  - Interactions of itraconazole with amphotericin B in the treatment of murine
      invasive candidiasis.
AB  - The interactions of amphotericin B and itraconazole were studied in murine
      invasive candidiasis. Candida albicans-infected mice were treated for 10
      consecutive days, 24 h after infection. Survival was monitored over 30 days and
      kidney cultures were done. Mice treated with amphotericin B (0.2 mg/kg/day
      intraperitoneally) or itraconazole (100 mg/kg/day by oral gavage in two divided
      doses/ day) had a 30-day survival of 20% or 40%. Concomitant administration of
      both drugs resulted in 100% mortality; 90% of mice treated with amphotericin B (1
      mg/kg/day) survived. With the combination, 100% were dead by day 28 (P < or =
      .001 vs. amphotericin B). With sequential therapy (i.e., 5 days with one drug and
      then 5 days with the other), survival was inferior to that with amphotericin B
      alone but similar to that with itraconazole alone. Kidney culture results
      confirmed the antagonism of the combination compared with amphotericin B alone.
      In treatment of murine invasive candidiasis, the concomitant or sequential use of
      amphotericin B and itraconazole results in a negative interaction.

PMID- 9607847
TI  - Phase I/IIa safety, immunogenicity, and efficacy trial of NYVAC-Pf7, a pox
      vectored, multiantigen, multistage vaccine candidate for Plasmodium falciparum
      malaria.
AB  - Candidate malaria vaccines have failed to elicit consistently protective immune
      responses against challenge with Plasmodium falciparum. NYVAC-Pf7, a highly
      attenuated vaccinia virus with 7 P. falciparum genes inserted into its genome,
      was tested in a phase I/IIa safety, immunogenicity, and efficacy vaccine trial in
      human volunteers. Malaria genes inserted into the NYVAC genome encoded proteins
      from all stages of the parasite's life cycle. Volunteers received three
      immunizations of two different dosages of NYVAC-Pf7. The vaccine was safe and
      well tolerated but variably immunogenic. While antibody responses were generally
      poor, cellular immune responses were detected in >90% of the volunteers. Of the
      35 volunteers challenged with the bite of 5 P. falciparum-infected Anopheles
      mosquitoes, 1 was completely protected, and there was a significant delay in time
      to parasite patency in the groups of volunteers who received either the low or
      high dose of vaccine compared with control volunteers.

PMID- 9607848
TI  - Interleukin-12-dependent mechanisms in the clearance of blood-stage murine
      malaria parasite Plasmodium berghei XAT, an attenuated variant of P. berghei
      NK65.
AB  - The mechanism of development of host resistance to blood-stage malarial infection
      was studied by use of an irradiation-induced attenuated variant, Plasmodium
      berghei XAT, obtained from a lethal strain, P. berghei NK65. The infection
      enhanced mRNA expression of interleukin (IL)-12 p40 and also of interferon (IFN)
      gamma, IL-4, IL-10, and cytokine-inducible nitric oxide synthase (iNOS) in
      spleen. Treatment of these mice with anti-IL-12 or anti-IFN-gamma led to the
      progression of parasitemia and fatal outcome. Anti-IL-12 treatment significantly
      reduced the secretion and mRNA expression of IFN-gamma and greatly diminished the
      augmentation of iNOS mRNA expression. In addition, recombinant IL-12
      administration delayed the onset of parasitemia because of the enhanced IFN-gamma
      production. These results suggest that blood-stage P. berghei XAT infection
      induces IL-12 production, which is important for the development of host
      resistance via IFN-gamma production.

PMID- 9607849
TI  - Glycine-valine dimorphism at the 86th amino acid of HLA-DRB1 influenced the
      prognosis of postschistosomal hepatic fibrosis.
AB  - Chinese patients (n = 113) with schistosomal hepatic fibrosis diagnosed by
      ultrasonography (grade I, II, or III) and 184 age- and sex-matched persons with
      no clinical information of schistosomal infection were typed for their HLA-DRB1
      alleles by DNA typing. There was no single allele that conferred susceptibility
      or resistance to fibrosis. However, there were three groups of alleles that
      showed decreased (resistant), increased (susceptible), or neutral frequency in
      the patients with fibrosis. The susceptible alleles, DRBI *1202, DRB1 *1404, and
      DRBI *1405, shared a valine at amino acid residue 86, whereas the resistant
      alleles, DRB1*11011, DRB1*0409, and DRB1*0701, all had glycine at position 86.
      Therefore, this study focused on the glycine-valine dimorphism at aa 86, which
      influences the depth of the P1 pocket in the antigen binding groove, and found
      that the 86th valine allele was significantly increased in the patients with
      fibrosis (odds ratio = 2.2; 95% CI = 1.34-3.61, corrected P < .05).

PMID- 9607850
TI  - Immunologic determinants of disease evolution in localized cutaneous
      leishmaniasis due to Leishmania major.
AB  - Localized cutaneous leishmaniasis caused by Leishmania major is polymorphic in
      its clinical presentation and evolution. Clinical and parasitologic features and
      disease evolution of 112 Tunisian patients was evaluated. The expression of
      interleukin (IL)-4, IL-6, IL-10, IL-12 (p40), interferon (IFN)-gamma, and tumor
      necrosis factor (TNF)-alpha mRNA was analyzed by reverse transcription-polymerase
      chain reaction in 73 biopsies. Cytokine mRNA expression varied individually over
      a wide range; TNF-alpha, IL-6, and IFN-gamma were detectable in >90% of lesions,
      IL-12 and IL-10 in 40% and 70%, respectively, and IL-4 in only 9%. Statistical
      analysis demonstrated positive association between the level of IL-12 and IFN
      gamma and the presence of parasites in the lesions. Unfavorable evolution of the
      lesions was positively associated with high IL-10, IL-12, and IFN-gamma mRNA
      expression. These results indicate that an unfavorable clinical outcome was not
      related to an inadequate Th1 cell response and suggest that the macrophage
      activating effect of IFN-gamma may be inhibited by the concomitant expression of
      IL-10.

PMID- 9607851
TI  - Tissue distribution of hantavirus antigen in naturally infected humans and deer
      mice.
AB  - The Sin Nombre virus (SNV) is the etiologic agent of hantavirus pulmonary
      syndrome in humans but does not cause disease in chronically infected deer mice
      (Peromyscus maniculatus), the natural host. In this study, murine antiserum
      raised against recombinant SNV nucleocapsid protein was utilized to localize
      viral antigen immunohistochemically in tissues from both humans (n = 20; 11
      positive, 9 negative) and deer mice (n = 6; 4 positive, 2 negative). Viral
      infection status was confirmed by Western blot or reverse transcriptase
      polymerase chain reaction. SNV antigen was detected in pulmonary and cardiac
      endothelium in both species, but positive cells in deer mice were rare. Other
      deer mouse tissues, including kidney, were negative; in contrast, vascular
      elements of several tissues from infected humans were positive, with strong
      staining of renal endothelium. The paucity of positive cells in chronically
      infected mice suggests a low virus burden compared with that of acutely infected
      humans.

PMID- 9607852
TI  - Analysis of the persistence of humoral and cellular immunity in children and
      adults immunized with varicella vaccine.
AB  - The persistence of humoral and cellular immunity to varicella-zoster virus (VZV)
      was evaluated in 60 children and 18 adults immunized with live attenuated VZV
      vaccine. At a mean of 5 years after vaccination, 93% of children and 94% of
      adults had IgG antibodies to VZV as determined by ELISA. VZV antibody
      concentrations were significantly higher at 5 years than at 1 year after
      immunization in children and adults. Cell-mediated immunity to VZV was detected
      in 87% of children and 94% of adults at 5 years. The mean stimulation index was
      significantly higher at 5 years than at 1 year among children and adults.
      Cytokine responses to VZV, including interleukin-2, interferon-gamma, and
      interleukin-10 were equivalent between children and adults at 5 years. In
      summary, varicella immunization induced long-term humoral and cellular immunity,
      and initial differences between cell-mediated responses in children and adults
      diminished over time.

PMID- 9607853
TI  - Spontaneous loss of viral episomes accompanying Epstein-Barr virus reactivation
      in a Burkitt's lymphoma cell line.
AB  - Life-long viral persistence is a hallmark of human herpesvirus infection. In the
      Epstein-Barr virus (EBV)-positive Burkitt's lymphoma (BL) cell line, Mutu,
      spontaneous loss of all viral episomes accompanied productive viral DNA
      replication. The molecular configuration of intracellular EBV DNA evolved from
      monoclonal episomes in cells retaining the original tumor phenotype to
      predominantly replicating linear DNA and, subsequently, only integrated forms in
      BL cells that had acquired the lymphoblastoid cell phenotype. Transient
      appearance of deleted, rearranged WZhet EBV DNA capable of disrupting viral
      latency, along with the integration of viral DNA into human chromosomes,
      indicates a genetic instability in the host cell which, if duplicated in vivo,
      may affect configuration and persistence of the viral genome in expanding
      malignant cell clones.

PMID- 9607854
TI  - Stability over time of serum antibody levels to human papillomavirus type 16.
AB  - The stability over time of serum IgG antibody levels to human papillomavirus type
      16 (HPV-16) was determined by comparing the HPV-16 capsid antibody levels in
      serial serum samples of an age-stratified random subsample of 1656 primiparous
      mothers resident in Helsinki who were followed until their second pregnancy, on
      average 29.5 months later. The correlation between the first and second pregnancy
      HPV-16 serum antibody levels of the same woman was high, even when >4 years had
      elapsed between pregnancies (r = .822). Between negativity, indeterminate
      results, or quartiles of positivity, the predictive values for being classified
      in the same category on both occasions ranged between 42% and 91%. Correlation
      coefficients, predictive values, and kappa coefficients between serial samples
      all were comparable with those of repeat analyses of the same sample, indicating
      that HPV capsid antibody levels are generally stable during several years of
      follow-up.

PMID- 9607855
TI  - High prevalence of antibodies to human herpesvirus 8 in relatives of patients
      with classic Kaposi's sarcoma from Sardinia.
AB  - A survey for antibodies to a recombinant small viral capsid antigen (sVCA) of
      human herpesvirus type 8 (HHV-8) was conducted in Sardinia, one of the world's
      highest incidence areas for classic Kaposi's sarcoma (KS). Prevalence of
      antibodies to HHV-8 sVCA was greatest in patients with KS (95%), followed by
      family members (39%) and a Sardinian control population age- and sex-matched to
      the relatives (11%). Within families, prevalence of antibodies was about equal
      among spouses, children, and siblings of KS patients, a finding that raises the
      possibilities of intrafamilial person-to-person or vertical transmission.
      Antibodies were detected 2-3 times more frequently in males than in females. The
      data show that prevalence of antibodies to HHV-8 sVCA correlates with the
      distribution of classic KS in a high- incidence area. Clustering of
      seroprevalence within some families suggests the presence of familial risk
      factors for active HHV-8 infection.

PMID- 9607857
TI  - GB virus C/hepatitis G virus infection: a favorable prognostic factor in human
      immunodeficiency virus-infected patients?
AB  - To investigate a possible influence of GB virus C (GBV-C) in immunocompromised
      patients, the prevalences of GBV-C RNA and anti-E2 antibody in 197 human
      immunodeficiency virus (HIV)-infected patients and in 120 control blood donors
      were studied. GBV-C RNA was detected in 33 of 197 HIV-infected patients (16.8%)
      compared with 1 in 120 blood donors (0.8%) (P < .001). Previous exposure to GBV-C
      (anti-E2 antibody-positive) was shown in 56.8% of HIV patients and in 9% of blood
      donors. GBV-C viremia was not associated with hepatitis. Despite approximately
      equal duration of HIV infection in all subgroups, the CD4 cell counts were
      significantly higher in GBV-C-viremic patients (344 cells/microL) compared with
      exposed (259 cells/microL) and unexposed (170 cells/microL) patients (P = .017
      and P < .001). Furthermore, Kaplan-Meier analysis demonstrated significantly
      better cumulative survival in GBV-C RNA-positive HIV-infected patients,
      suggesting that GBV-C might be a favorable prognostic factor in HIV disease.

PMID- 9607858
TI  - Cross-clade inhibition of human immunodeficiency virus type 1 primary isolates by
      monoclonal anti-CD4.
AB  - A murine monoclonal antibody (MAb) with human CD4 specificity was tested for the
      ability to inhibit primary human immunodeficiency virus type 1 (HIV-1) isolates
      clades A through E. Human peripheral blood mononuclear cells (PBMC) were used as
      target cells for infectivity. The HIV-1 primary isolates were examined for the
      capacity to infect PBMC targets in the presence or absence of the anti-CD4 MAb,
      designated P1. P1 broadly inhibited clade A, C, D, and E isolates, based on a
      reduction of HIV-1 p24 antigen concentrations compared with untreated controls.
      Little to no virus-inhibiting activity was observed with a primary HIV-1 clade B
      isolate, designated BZ167. Additionally, a second primary clade B isolate was
      efficiently inhibited from infecting PBMC targets by P1. The data indicate that
      P1 exhibits group-specific inhibiting activity against non-clade B primary HIV-1
      isolates in vitro.

PMID- 9607856
TI  - GB virus C infection in patients with primary antibody deficiency.
AB  - Sera from 77 patients with common variable immunodeficiency (CVID) were tested
      for GB virus C (GBV-C) RNA, because they are prone to unexplained chronic
      hepatitis, and from 28 patients with X-linked agammaglobulinemia (XLA) who have a
      similar primary antibody deficiency but are not prone to hepatitis. Eight CVID
      and 8 XLA patients were positive; 6 positive CVID and 3 XLA patients had abnormal
      liver enzymes, explained in 3 by either hepatitis B or C virus infection. Most
      patients tested had antibodies to the E2 antigen of GBV-C, apparently passively
      acquired from their immunoglobulin therapy. The high prevalence of GBV-C viremia
      in CVID and XLA patients is probably explained by their long-term exposure to
      blood products. Our data indicate that GBV-C does not cause chronic hepatitis in
      immunocompromised XLA patients and is not the cause of chronic non-B or -C
      hepatitis in the majority of CVID patients.

PMID- 9607859
TI  - Human immunodeficiency virus proviral DNA from peripheral blood and lymph nodes
      demonstrates concordant resistance mutations to zidovudine (codon 215) and
      didanosine (codon 74). Division of AIDS Treatment Research Initiative 003 Study
      Group.
AB  - Genotypes that confer drug resistance were evaluated in human immunodeficiency
      virus (HIV) proviral DNA obtained from peripheral blood mononuclear cells (PBMC)
      and lymphoid tissue at baseline and after 8 weeks of therapy with zidovudine
      alone or in combination with didanosine from 22 patients (8 zidovudine-naive and
      14 zidovudine-experienced). There was evidence of zidovudine resistance at codon
      215 in 27.3% (6/22) of patients. All 20 patients evaluable for codon 74 (site of
      didanosine resistance) had virus that remained wild type during the 8-week study
      period. When HIV proviral DNA from PBMC was compared with that from lymphoid
      tissue, 94.7% (18/19) of evaluable samples were concordant at codon 215 at
      baseline, while 85.7% (12/14) were concordant at week 8. Resistance in PBMC (but
      not in lymphoid tissue) developed in 1 of 8 zidovudine-naive patients; an
      increased proportion of resistant strains in PBMC (but not in lymphoid tissue)
      was observed in 2 of 14 zidovudine-experienced patients. These results suggest
      high concordance for drug resistance mutations in HIV proviral DNA from blood and
      lymph node tissue.

PMID- 9607860
TI  - Effect of granulocyte colony-stimulating factor (G-CSF) in human immunodeficiency
      virus-infected patients: increase in numbers of naive CD4 cells and CD34 cells
      makes G-CSF a candidate for use in gene therapy or to support antiretroviral
      therapy.
AB  - The potential of granulocyte colony-stimulating factor (G-CSF) to mobilize CD4
      cells and/or CD34 cells for use in gene therapy or to support antiretroviral
      therapy was examined. Ten human immunodeficiency virus-infected patients were
      treated with G-CSF (300 microg/day) for 5 days. Numbers of CD4 and CD34 cells
      were measured. To examine the numbers of naive and memory type CD4 cells, CD4
      cell coexpression of CD45RA and CD45RO was measured. Functionality of mobilized
      CD4 cells was examined by use of the proliferation assay and interleukin-2 ELISA.
      The number of CD34 cells increased from 1.50 to 20.01/microL (P < .002). The CD4
      cell count increased from 236 to 452/microL (P < .002). The CD45RA/CD45RO ratio
      increased from 0.50 to 0.57 (P < .03). Mobilized CD4 cells were functionally
      intact. In conclusion, G-CSF induced increases in numbers of CD34 cells and CD4
      cells in HIV-infected patients. Furthermore, the fraction of naive CD4 cells
      increased. These findings have implications for the design of immunotherapy or
      gene therapy protocols.

PMID- 9607861
TI  - Apparent enhancement of perinatal transmission of human immunodeficiency virus
      type 1 by high maternal anti-gp160 antibody titer.
AB  - The presence of antibodies able to enhance infection in vitro in sera from human
      immunodeficiency virus (HIV)-1-infected patients raises the possibility that
      antibodies exert a deleterious activity during natural infection. The anti-HIV-1
      humoral response and plasma HIV-1 RNA were measured in a cohort of 98 infected
      mothers, included in the French Prospective Study on Pediatric HIV Infection, 49
      of whom transmitted HIV to their children. Transmission from mother to child was
      associated with antibody responses to the envelope gp160 (P = .009 for serum
      dilution of 1/400) and to a highly conserved domain of the transmembrane
      glycoprotein (P = .055 for serum dilution of 1/400) and with plasma HIV-1 RNA
      levels (P < .0001). Multivariate logistic regression indicated that a high anti
      gp160 response and a high plasma virus load are independent risk factors for
      perinatal transmission of HIV-1 (odds ratio, 3.4; 95% confidence interval, 1.1
      9.9 for anti-gp160; odds ratio, 2.8; 95% confidence interval, 1.6-5.0 for virus
      load).

PMID- 9607862
TI  - High levels of human immunodeficiency virus type 1 in blood and semen of
      seropositive men in sub-Saharan Africa.
AB  - High levels of human immunodeficiency virus type 1 (HIV-1) replication, as
      reflected in HIV-1 RNA concentrations in blood and semen, probably contribute to
      both rapid disease progression and enhanced sexual transmission. Semen and blood
      were collected from 49 Malawian and 61 US and Swiss (US/Swiss) HIV-1-seropositive
      men with similar CD4 cell counts and no urethritis or exposure to antiretroviral
      drugs. Median seminal plasma and blood plasma HIV-1 RNA concentrations were >3
      fold (P = .034) and 5-fold (P = .0003) higher, respectively, in the Malawian men.
      Similar differences were observed in subsets of the Malawian and US/Swiss study
      groups matched individually for CD4 cell count (P = .035 and P < .002,
      respectively). These observations may help explain the high rates of HIV-1 sexual
      transmission and accelerated HIV-1 disease progression in sub-Saharan Africa.

PMID- 9607863
TI  - Proinflammatory cytokine and human immunodeficiency virus RNA levels during early
      Mycobacterium avium complex bacteremia in advanced AIDS.
AB  - The relationship between Mycobacterium avium complex (MAC) bacteremia and
      proinflammatory cytokine and human immunodeficiency virus type 1 (HIV-1) RNA
      levels in AIDS was investigated. During a prospective study, blood samples were
      drawn monthly for mycobacterial cultures. Sera were available at baseline and
      onset of MAC bacteremia from 20 cases and at corresponding times from 19
      controls. Mean interleukin-6 (IL-6) levels were 154% greater at the time of MAC
      bacteremia in cases than in controls. The IL-6 levels correlated with body
      temperature, serum tumor necrosis factor (TNF-alpha) levels, and alkaline
      phosphatase levels (P < or = .004 for each). Although TNF-alpha levels tended to
      rise more in MAC patients than in controls, the difference was not significant.
      However, among both cases and controls, serum TNF-alpha levels rose significantly
      from baseline to the time of last sample, irrespective of MAC infection (P =
      .015). Bacteremia was not associated with increased serum HIV-1 RNA levels. Thus,
      early MAC bacteremia is associated with increases in serum IL-6 levels, while TNF
      alpha levels rise over time during advanced AIDS.

PMID- 9607864
TI  - Genotypic and phenotypic changes in the emergence of Escherichia coli O157:H7.
AB  - Escherichia coli O157:H7 is a foodborne pathogen distinguished from typical E.
      coli by the production of Shiga toxins (Stx) and the inability to ferment
      sorbitol (SOR) and to express beta-glucuronidase (GUD) activity. An allele
      specific probe for the GUD gene (uidA) and multilocus enzyme electrophoresis were
      used to elucidate stages in the evolutionary emergence of E. coli O157: H7. A
      point mutation at +92 in uidA was found only in O157:H7 and its nonmotile
      relatives, including a SOR+ O157:H clone implicated in outbreaks of hemolytic
      uremic syndrome in Germany. The results support a model in which O157:H7 evolved
      sequentially from an O55:H7 ancestor, first by acquiring the Stx2 gene and then
      by diverging into two branches; one became GUD- SOR- , resulting in the O157:H7
      clone that spread worldwide, and the other lost motility, leading to the O157:H
      clone that is an increasing public health problem in Europe.

PMID- 9607865
TI  - Serogroup B, electrophoretic type 15 Neisseria meningitidis in Canada.
AB  - Invasive meningococcal disease is nationally reportable in Canada. In recent
      years, a serogroup C genotype, designated electrophoretic type 15 (ET15), has
      been the most frequently isolated meningococcal genotype in Canada and has caused
      epidemics across the country. Between August 1993 and September 1995, there were
      9 cases of invasive meningococcal disease caused by a variant of this genotype,
      expressing group B capsular polysaccharide. The appearance of serogroup B:ET15
      was related temporally and geographically to mass immunization campaigns designed
      to control serogroup C meningococcal disease in Canada. Since there is no vaccine
      available to control serogroup B meningococcal disease, the appearance of this
      variant may have public-health significance if it demonstrates the same epidemic
      potential as its serogroup C counterpart.

PMID- 9607866
TI  - Vaccination with a Haemophilus influenzae type b conjugate vaccine reduces
      oropharyngeal carriage of H. influenzae type b among Gambian children.
AB  - The effect of a Haemophilus influenzae type b (Hib) polyribosylribitol phosphate
      tetanus toxoid conjugate vaccine (Hib/PRP-T) on oropharyngeal carriage of Hib was
      studied during an efficacy trial in Gambian infants. Children were vaccinated
      with Hib/PRP-T and diphtheria-tetanus toxoids-pertussis (DTP) or DTP alone at
      ages 2, 3, and 4 months. Groups of 1000 children aged 1-2 years were studied each
      year for 4 years. Hib was detected by production of a halo on antiserum agar
      plates. Carriage was significantly lower among children fully vaccinated with
      Hib/PRP-T given with DTP (4.4%; 95% confidence interval [CI], 3.8%-5.7%) than
      among children fully vaccinated with DTP alone (11.0%; 95% CI, 8.9%-13.0%)
      (protective effect adjusted by year = 60%; 95% CI, 44%-72%; P < .001). Hib
      carriage varied by year among nonvaccinated children. Hib conjugate vaccines are
      likely to produce a herd protective effect in underdeveloped communities, as
      recorded in Europe and the United States.

PMID- 9607867
TI  - Humoral immune response to tetanus-diphtheria vaccine given during extended use
      of chloroquine or primaquine malaria chemoprophylaxis.
AB  - Immune suppression resulting from prolonged chemoprophylaxis and potential drug
      vaccine interaction were investigated within the context of a randomized placebo
      controlled trial that compared daily primaquine or weekly chloroquine
      administration for malaria prevention. After 11 months of prophylaxis, adult male
      subjects received a tetanus-diphtheria (Td) vaccination. Prophylaxis continued 4
      weeks longer. Anti-tetanus and anti-diphtheria antibody levels were measured by
      ELISA at baseline and at 1, 3, 7, and 14 months after Td vaccination. All groups
      were comparable at baseline. Immunization triggered significant increases in anti
      tetanus and anti-diphtheria IgG levels over each group's pre-Td baseline levels
      and those of an unvaccinated control group. Geometric mean anti-tetanus titers
      (GMTs) in the primaquine group were significantly higher than those of the
      placebo group at 1, 3, and 14 months. Anti-tetanus GMTs in placebo and
      chloroquine groups declined over 14 months to levels comparable to those of
      unvaccinated controls, but levels in the primaquine group remained significantly
      higher than in controls.

PMID- 9607868
TI  - Risk factors for repeated gonococcal infections: San Francisco, 1990-1992.
AB  - Gonococcal (GC) infections are very common and are sustained by a core group of
      persons who often have repeated GC infections. Identifying individual risk
      factors for repeated GC infection is essential so that infection control programs
      can develop better strategies for decreasing the incidence of GC infection. A
      case-control study among high-risk persons found that being African American,
      having previous chlamydia infection, and having less than a high-school education
      were associated with repeated GC infections. Remarkably, measures of sexual
      behavior and access to health care were not associated with repeated GC
      infections. These findings suggest that among high-risk persons, the community
      prevalence of GC infection is more important in predicting risk for repeated GC
      infections than individual behavior. Interventions should include continued use
      of resources in high-prevalence communities and better understanding of the roles
      social and economic discrimination play in the risk for GC infections.

PMID- 9607869
TI  - High incidence of early postnatal transmission of human immunodeficiency virus
      type 1 in Bangui, Central African Republic.

PMID- 9607870
TI  - Antiviral CD4 cell response in simian immunodeficiency virus-infected macaques.

PMID- 9607871
TI  - Maternal enterovirus infection.

PMID- 9607872
TI  - Nondiagnostic bone marrow in parvovirus B19-related anemia in AIDS: confounding
      effect of prior transfusion?

PMID- 9607873
TI  - Epidemiology of invasive streptococcal infections.

PMID- 9607874
TI  - Antibiotic resistance and O antigen expression in Escherichia coli.

PMID- 9607875
TI  - Prevention of aspergillosis in bone marrow transplantation.

PMID- 9607876
TI  - Clinical manifestations of Plasmodium falciparum malaria.

PMID- 9607877
TI  - The effect of triathlon on urinary excretion of enzymes and proteins.
AB  - In order to investigate the effect of triathlon and renal function of normal
      subjects, we evaluated the excretion of urinary enzymes and proteins before and
      after triathlon. From 6 subjects samples were obtained 24 hours after the first
      urine collection. We performed quantification of urinary total protein, beta2
      microglobulin (beta2-M), N-acetyl-beta-D-glucosaminidase activity (NAG), and
      concentration of urinary creatinine from each participant. There was a
      significant increase in urinary total protein excretion immediately after
      triathlon (p<0.01). The urinary beta2-M and NAG excretions after triathlon were
      higher than the initial values. Post-exercise proteinuria in one subject
      persisted until the next morning, whereas the increased excretion of urinary
      beta2-M and NAG returned to the pre-exercise level at least 24 hours after
      triathlon. It appears to be reasonable to presume that glomerular damage may
      persist in some subjects who do heavy exercise.

PMID- 9607878
TI  - Extracorporeal shock wave lithotripsy and glycosaminoglycans in urine.
AB  - In 50 calcium oxalate stone-forming patients, the total excretion of
      glycosaminoglycans (GAGs) and of four of its subgroups [chondroitin-4-sulfate (CS
      A), chondroitin-6-sulfate (CS-C), dermatan sulfate (DS), and hyaluronic acid
      (HY)] were investigated before ESWL and on the following 5 days. The standard
      value was determined by reference to a group of healthy test subjects. The
      excretion of GAGs was significantly higher in healthy test persons than in stone
      forming patients. Twenty-four hours after ESWL, GAG excretion increased
      significantly but returned to normal values in the course of three days. ESWL had
      no influence on the proportional composition of GAG subgroups CS-A, CS-C, DS and
      HY. The increase in GAG excretion after ESWL indicates a transient injury of
      renal tissue and of the mucous layer lining the urothelium, respectively. This
      lesion, however, can be regarded as temporary with restitutio ad integrum later.

PMID- 9607879
TI  - Subureteric polydimethylsiloxane injection in the treatment of vesico-ureteric
      reflux.
AB  - Endoscopic treatment of vesico-ureteric reflux is a viable alternative to open
      surgery. We evaluated the effectiveness of polydimethylsiloxane in the endoscopic
      treatment of vesico-ureteric reflux. In the period between September 1994 and
      March 1996, 30 ureteral units of 20 children with vesico-ureteric reflux were
      treated by means of subureteric polydimethylsiloxane injection. Median age was 8
      years in the group including 8 female and 12 male patients. Of the 30 ureteral
      units, 26 had no reflux at the end of the first injection. Two of the remaining
      four units were not refluxing after the second injection procedure. Contralateral
      reflux was observed postoperatively in two of the eleven patients who were
      treated for unilateral disease. It seems that endoscopic polydimethylsiloxane
      injection is an effective procedure in the treatment of vesico-ureteric reflux.

PMID- 9607880
TI  - A new ancient irrigation therapy for childhood renal candidiasis.
AB  - Methylene blue (MB) alone, MB metabolites in the urine and the effect of MB plus
      alkalization on Candida species were determined. MB was used for the treatment of
      childhood renal candidiasis (CRC) in 3 patients as an irrigating solution.
      Besides irrigation, fluconazole 3 mg/kg/day intravenously and MB 0.2 mg/kg/day
      were administered perorally. Urine cultures were cleared of Candida. DMSA scans
      obtained after 6 months showed no evidence of scarring. MB can be used for
      irrigation of the urinary tract, with fewer side effects than amphotericin B
      (AB). Additionally we advocate the use of ureteral catheters instead of
      nephrostomy in the treatment of CRC.

PMID- 9607881
TI  - Severe unremitting cystitis progressing to cystectomy.
AB  - We report on patients with severe intractable idiopathic cystitis, one of whom
      progressed to cystectomy. The implications of non-infective, non-interstitial
      cystitis are discussed.

PMID- 9607882
TI  - Investigations of urinary cadmium content in patients with urinary bladder
      carcinoma.
AB  - In the present paper authors investigated urinary cadmium content in 10 patients
      with urinary bladder carcinoma using atomic spectrometry. It was found that in
      60% of these patients it was increased. These results might indicate an
      involvement of cadmium in carcinogenesis.

PMID- 9607883
TI  - Leiomyoma of the bladder: a case report.
AB  - A case of leiomyoma of the urinary bladder in a 20-year-old man is reported. The
      patient presented with severe frequency and perineal burning at the end of
      urination along with microscopic haematuria. Enucleation of the tumour was
      performed because transurethral biopsy revealed leiomyoma. The prognosis of these
      tumours is excellent.

PMID- 9607884
TI  - Ceramic coagulation tip for interstitial thermoablation of the prostate: first
      experiments.
AB  - A direct electrically heated ceramic coagulation tip for interstitial
      thermoablation has been developed. Both the coagulation tip and a laser system
      (Medilas 4060) were tested in vitro to compare their efficacies. We have obtained
      coagulation necroses of similar sizes. The electrical coagulation tip as opposed
      to laser coagulation is a new therapeutic option for the therapy of high risk
      patients with symptomatic benign prostatic hyperplasia. Because of the materials
      used and the principle of heating involved, certain economic and safety
      advantages over the laser system are offered.

PMID- 9607885
TI  - Tuberculosis of the prostate.
AB  - We present five cases of tuberculous prostatitis. In all cases this was an
      incidental histologic finding after transurethral prostatectomy. The patients
      were all treated with an antituberculous drug regimen. A literature review of
      this rare condition is included.

PMID- 9607886
TI  - High dose intravenous oestrogen (fosfestrol) in the treatment of symptomatic,
      metastatic, hormone-refractory carcinoma of the prostate.
AB  - OBJECTIVE: High dose intravenous stilboestrol has a direct cytotoxic effect on
      prostatic carcinoma cells. The purpose of this study was to assess subjective and
      objective responses in a select group of patients with metastatic, hormone
      refractory carcinoma of the prostate with severe generalized bone pain in
      association with symptoms of advanced local disease. PATIENTS AND METHODS:
      Seventeen patients with metastatic carcinoma of the prostate, who had relapsed
      following a good initial response to androgen ablation, were treated as
      inpatients with once daily intravenous injection of 1104 mg diethylstilboestrol
      diphosphate (Honvan, Asta Medica, Cambridge, UK) for 7 days. The hormone
      refractory status was confirmed by castrate serum testosterone levels. All the
      patients had failed to respond to second-line hormone manipulation and had
      progressive disease. All the patients had generalized bone pain, 11 also had
      symptoms of bladder outlet obstruction, 3 had recurrent haematuria and 3 had
      both. The mean age was 74 years (range 59-83), mean time to chemical relapse
      (rising PSA) was 29 months (range 1-70), and mean time to clinical relapse was 37
      months (range 6-98). The WHO pain score, performance status score, and a patient
      specific quality of life (daily living activity) were used as the subjective
      measures and the serum PSA as an objective marker. All the parameters were
      recorded before, during and up to three months after treatment. RESULTS: Two
      patients had a transient relief of bone pain with the pain score reducing by two
      points. Overall, the pain and performance scores and the local symptoms did not
      improve. The PSA level continued to rise in all patients. Despite parenteral pre
      medication with pethidine and cyclizine, all the patients suffered nausea and
      pain following the injection. One patient died on the fifth day of treatment from
      a myocardial infarction and 4 developed deep vein thrombosis. All the patients
      required further symptom control measures. CONCLUSION: High dose intravenous
      stilboestrol causes considerable morbidity without any objective or subjective
      response in the treatment of patients with symptomatic, hormone-refractory
      metastatic carcinoma of the prostate.

PMID- 9607887
TI  - The effects of extensive vas mobilization on testicular histology during
      orchiopexy.
AB  - We were aware that extensive mobilization of vas deferens during orchiopexy could
      cause secondary infertility due to testicular damage and/or functional
      obstruction of the vas deferens. We decided to perform this experimental study in
      order to document the effects of this procedure on the testis. Thirty adult
      fertility-proven New Zealand white rabbits were randomly divided into 3 groups.
      Ten rabbits underwent extensive mobilization of the vas deferens and the other 10
      rabbits had vasectomy on the left side. The remaining 10 rabbits were explored on
      the left side only and were considered sham controls. Four weeks later all
      rabbits underwent bilateral orchiectomy. Mean seminiferous tubular diameters and
      Johnsen's testicular biopsy scores were noted. Comparison of the three groups
      showed that vas mobilization and vasectomies cause no effect on the viability of
      testis, however, significant testicular histological changes, which were
      different from the controls and contralateral testis, were observed. We concluded
      that during any surgical intervention involving the inguinal canal, vascular and
      neural supports of the vas deferens should be preserved as much as possible in
      order to avoid iatrogenic damages to the testis.

PMID- 9607888
TI  - Metastatic testicular germ cell tumour: the role of salvage surgery.
AB  - To assess the clinical characteristics of metastatic testicular germ cell tumour,
      response to chemotherapy and outcome of salvage surgery for residual mass were
      analyzed. Patients with complete response were carefully watched. Salvage surgery
      was performed in 14 patients after chemotherapy. Resected specimens showed 7
      necrosis/fibrosis, 5 teratoma, 1 cancer, and 1 benign schwannoma. Only
      necrosis/fibrosis was found in cases without teratoma in the primary tumour.
      Existence of teratomatous elements in a primary tumour suggests that cancer or
      teratoma is present in the residual tumour. Furthermore, tumour reduction rate
      could not predict their presence in resected specimens.

PMID- 9607889
TI  - Growing mediastinal metastatic tumour in a patient with burned out testicular
      cancer.
AB  - A 27-year-old man was referred to us for resection of a post-chemotherapy growing
      mass in the mediastinum. He had been treated with 4 courses of combination
      chemotherapy for his testicular cancer. The primary lesion was burned out and the
      anterior mediastinal metastatic tumour contained immature teratoma. After
      normalization of tumour marker levels, the mediastinal mass was resected
      completely and the resected specimen showed teratoma with rhabdomyosarcoma. Two
      rare clinical conditions have been seen in this case.

PMID- 9607890
TI  - Is apolipoprotein-(a) an important indicator of vasculogenic erectile
      dysfunction?
AB  - We aimed to investigate whether high peripheral and cavernosal plasma levels of
      apolipoprotein-(a) [Lp (a)] is an indicator for vasculogenic erectile
      dysfunction. We determined Lp (a), total cholesterol (TC), triglyceride (TG) and
      high density lipoprotein (HDL) levels in peripheral and cavernosal blood in 39
      patients with erectile dysfunction. Thirty-nine impotent patients have been
      divided into two groups: vasculogenic erectile dysfunction (VED) and
      nonvasculogenic erectile dysfunction (NVED), according to colour Doppler
      ultrasonic flowmetry, dynamic infusion cavernosometry, and the pressure
      difference between the brachial arterial systolic pressure and cavernosal
      arterial systolic pressure measurements. Biochemical values were compared in both
      groups. Lp (a) and TC levels were higher in both peripheral and cavernosal
      samples of VED group than in NVED group, with no differences between peripheral
      and cavernosal blood levels within the same groups. There were no significant
      changes in TG and HDL levels in either group. The detection of more than 31 mg/dl
      in Lp (a) level solely shows the vascular origin with a sensitivity and
      specificity of 95 and 82.3%, respectively. High Lp (a) levels can be considered
      an indicator of vasculogenic erectile dysfunction.

PMID- 9607891
TI  - Papaverine plus prostaglandin E1 versus prostaglandin E1 alone for intracorporeal
      injection therapy.
AB  - PURPOSE: A study comparing intracorporeal injection of prostaglandin E1 (one-drug
      solution) and papaverine plus prostaglandin E1 (2-drug solution) for treatment of
      impotence. MATERIALS AND METHODS: A total of 100 impotent patients had
      intracorporeal injections of the one-drug and 2-drug solution alternatively in 3
      sessions. The quality and duration of erections were assessed. RESULTS: Seventy
      five per cent of the patients developed full erection with the 2-drug solution
      compared to 50% with the one-drug solution. The average duration of erections was
      60 minutes and 45 minutes, respectively. The complication rate was higher for the
      2-drug solution. CONCLUSION: Papaverine plus prostaglandin E1 is superior to
      prostaglandin E1 alone for treatment of impotence, but has a higher rate of
      complications. Intracavemous injection of vasoactive drugs is a very effective
      and important way for treatment of impotence. Papaverine plus prostaglandin E1
      had been used for treatment of impotence alone or combined. A blind study was
      done to compare efficiency and complication rates of intracavemous injection of
      papaverine plus prostaglandin E1 (2-drug solution) with prostaglandin E1 alone.

PMID- 9607892
TI  - Schwannoma of the penis: report of a case and review of the literature.
AB  - A case of schwannoma located in the penile shaft in a 65-year-old male is
      described. Special stain using S-100 immunoperoxidase was useful in establishing
      the diagnosis in this case. We reviewed the literature on penile schwannoma and
      focussed on the diagnosis of this rare ailment.

PMID- 9607893
TI  - Pericentric inversion of chromosome 9 in infertile men.
AB  - Reproductive condition was studied in 6 infertile men with pericentric inversion
      of chromosome 9. Semen analyses revealed one azoospermia, one oligozoospermia,
      three asthenozoospermias and one normozoospermia. Four cases showed normal levels
      of plasma gonadotropins and testosterone. The response of plasma testosterone to
      human chorionic gonadotropin was within the normal range in all cases. However,
      the administration of LH-RH resulted in abnormal response of plasma gonadotropin
      in all patients. These results indicate that infertile males with pericentric
      inversion of chromosome 9 have an abnormality in the hypothalamic-pituitary
      testicular axis.

PMID- 9607894
TI  - Membranoproliferative glomerulonephritis associated with small cell lung
      carcinoma.
AB  - An association between nephropathy and malignant solid tumours or with
      lymphoproliferative disorders was repeatedly reported. This association is mainly
      manifested by a nephrotic syndrome. In Lee's study [14], 11% of the adult
      nephrotics whom they had seen over a ten-year period developed a carcinoma.
      Membranous glomerulonephritis (MGN) is the most common glomerular disease
      associated with malignant solid tumour; the association of membranoproliferative
      glomerulonephritis (MPGN) with solid tumour is still uncommon. Although lung
      carcinoma is relatively common, the incidence of glomerular involvement with this
      tumour is quite rare. To date, only a few cases of lung cancer associated with
      nephrotic syndrome or glomerulonephritis have been reported by various authors.
      MGN is the most common glomerular lesion associated with these cases; however,
      MPGN has not been reported to be associated with lung cancer before. We report on
      a 45-year old man with nephrotic syndrome due to MPGN which in this case seemed
      to be a component of the paraneoplastic syndrome.

PMID- 9607895
TI  - Urinary cAMP activity in chronic renal failure.
AB  - Forty-six patients with chronic renal failure and 17 healthy controls were
      examined to determine their urinary cyclic adenosine monophosphate (UcAMP)
      levels. In the study group, UcAMP levels were found to average 1542 picomoles; in
      the controls, 4612 pmoles (P<0.001). UcAMP activity decreased in tandem with the
      decline of the glomerular filtration rate. Hypertension was not found to have an
      additional effect on UcAMP levels, and there was no statistical difference in
      UcAMP levels between the normotensive and hypertensive patients (P>0.05).

PMID- 9607896
TI  - Sclerosing encapsulating peritonitis.
AB  - In this report, three cases of sclerosing encapsulating peritonitis (SEP) are
      described; two of them were associated with pleural and/or pericardial effusions.

PMID- 9607897
TI  - Quantitative analysis of the renal changes in Balkan endemic nephropathy.
AB  - The volume densities of the cortical interstitium (CI), glomeruli and proximal
      tubular epithelium have been investigated on a sample involving 18 patients
      suffering from Balkan endemic nephropathy (BEN), classified into three groups
      with regard to the clearance of 99mTc-DTPA. In comparison with the control group,
      the evolution of the disease is marked by a significant increase of the CI volume
      (p<0.001), as well as a significant reduction of glomerular (p<0.01) and tubular
      volume densities (p<0.001). The most intensive changes of CI and glomerular
      volumes are characteristic of the initial stage of the disease when glomerular
      filtration (GF) has shown no signs of deterioration yet. On the other hand, a
      significant reduction of the tubular epithelium volume density is characteristic
      of the advanced stages. The specified changes, particularly those taking place at
      the level of interstitium bear the key responsibility for the BEN progression.
      However, a number of links constituting the chain of BEN morphogenesis remained
      insufficiently clarified. This urges for a precise quantification of all
      histological changes taking place in different stages of the disease, starting
      from the earliest, in order to get a better insight into the order and dynamics
      of their occurrence.

PMID- 9607898
TI  - Hepatocyte-based bioartificial liver support: past, present and future.

PMID- 9607899
TI  - Clinical study on lung cancer as a second primary cancer.
AB  - This study evaluates the effect of a previous cancer on the clinical
      characteristics and the outcome of lung cancer patients. The 313 primary lung
      cancer patients operated on in the Osaka University Hospital during the period
      1984-1993 were reviewed. Of those, 37 had a history of previous cancer. In the
      lung cancer patients with a history of previous cancer, 20 had adenocarcinomas,
      14 had squamous cell carcinomas, while 3 had other cancers. The previous
      malignancies included 13 gastric cancers, 10 head and neck cancers, 6 colorectal
      cancers, and 8 others. The pathological stage was 17 stage I, 1 stage II, 15
      stage IIIA, 1 stage IIIB, and 3 stage IV. The 5-year survival rate was 37.9%. In
      patients without a history of previous cancer, there were 139 adenocarcinomas,
      100 squamous cell carcinomas, and 37 others. The pathological stage was 126 stage
      I, 33 stage II, 74 stage IIIA, 23 stage IIIB, and 20 stage IV. The 5-year
      survival rate was 43.3%. There were no significant differences in the cell type,
      stage, or survival between the lung cancers found as the first and second
      cancers. Lung cancer patients with a history of previous cancer are expected to
      respond to a resection as well as those with lung cancer appearing as their first
      cancer.

PMID- 9607900
TI  - Primary anastomosis of the trachea: management and pitfalls.
AB  - Twenty-four patients with tracheal lesions were managed by various procedures,
      including primary anastomosis in 16, tracheoplasty in 2, and a terminal
      tracheostomy in 6. The patients undergoing anastomosis included 4 with primary
      tumors, 7 with secondary tumors, and 5 with benign stricture. Except for 2
      patients, there was no leakage or stenosis after a resection of from two to nine
      tracheal rings. There were 4 patients in whom the laryngeal nerve was paralyzed
      on one side prior to resection and then was sacrificed on the other side because
      of tumor involvement. Because of difficulty in swallowing, the outcome was not
      satisfactory in the 3 patients despite a good anastomosis. Cricotracheal
      anastomosis was performed in 3 patients, and thyrotracheal anastomosis in 1. Two
      patients in whom the trachea and esophagus communicated were treated using
      pedicled intercostal muscle grafts. Tracheal stenosis can be observed in various
      pathological conditions. Consequently, the optimal treatment varies from patient
      to patient according to the type of a disease, the location and extent of a
      disease, and the condition of the laryngeal nerve, while it is also important to
      carefully select the most appropriate anesthetic method, approach, and type of
      reconstruction.

PMID- 9607901
TI  - Abdominal aortic aneurysm repair with arterial branch reconstruction: utility of
      the temporary bypass technique.
AB  - Between June 1992 and May 1996, five patients underwent an abdominal aortic
      aneurysm (AAA) repair with concomitant arterial branch reconstruction. All of the
      patients were males ranging in age from 55 to 66 years (mean: 61.6 years). The
      operations were performed for a localized abdominal aortic dissection, a
      pseudoaneurysm after patch angioplasty of a supraceliac AAA, a pararenal AAA, a
      total AAA with retrograde descending thoracic aortic dissection, and a
      supraceliac AAA after an infrarenal AAA repair. All patients underwent bilateral
      renal artery (RA) reconstruction. Three patients also had a concomitant
      reconstruction of the superior mesenteric artery ad celiac axis. The renal
      arteries were preferentially reconstructed. Visceral circulation during aortic
      cross-clamping was maintained via a temporary bypass circuit. A temporary
      division of the left renal vein was necessary in two patients. Overall, the mean
      renal ischemia time was 17.2min (range: 10 to 32 min). There was one
      perioperative death due to sepsis from a graft infection. Another patient died 6
      months postoperatively due to pyothorax. One patient required postoperative
      hemodialysis for 1 month. Based on the above findings, the temporary bypass
      technique is thus considered to be useful for maintaining physiologic organ
      perfusion during aortic clamping without the need to use any complicated devices.

PMID- 9607902
TI  - The clinical significance of performing preoperative angiography of the internal
      thoracic artery in coronary artery bypass surgery.
AB  - This study was designed to clarify the clinical significance of and indications
      for performing preoperative internal thoracic artery (ITA) angiography in
      patients undergoing coronary artery bypass surgery. A total of 300 possible
      candidates for coronary artery bypass grafting (CABG) underwent ITA angiography
      during diagnostic catheterization. Semi-selective angiography of bilateral ITAs
      were performed by injecting contrast medium manually with a 5-F right Judkins
      coronary catheter. The posteroanterior view of the arteriograms was recorded on a
      35-mm cine film or a cut-film. Unusual angiographic findings of the ITAs were
      observed in nine patients (3%). These findings included: an atrophic ITA in three
      patients with ipsilateral subclavian artery occlusions; enlarged ITAs giving
      collaterals to the lower extremities in one patient with extensive aortoiliac
      occlusive disease; occluded ITAs in one patient with Takayasu's arteritis and two
      patients with a history of CABG; and a small but nonsclerotic ITA in one patient.
      Atherosclerotic occlusive ITAs were found in only one patient. Thus, we concluded
      that routine preoperative angiography of the ITA is not necessary because it is
      rarely affected by atherosclerosis. However, it should be performed for any of
      the following reasons: a cervical or supraclavicular bruit; an upper extremity
      blood pressure difference of greater than 20 mmHg; an extensive aortoiliac
      occlusion; and certain disorders such as Takayasu's arteritis or Kawasaki
      disease, or a history of open heart surgery.

PMID- 9607903
TI  - Histological evaluation of the effects of intraarterial chemotherapy for advanced
      breast cancer: a long-term followup study with respect to the survival rate.
AB  - To evaluate the effects of intraarterial infusion chemotherapy (IAIC) for
      advanced breast cancer, we examined the grade of histological responses of
      preoperative IAIC on tumors at the time of operation and estimated the patients'
      prognoses for 19 years. IAIC was done preoperatively using timely epochal
      anticancer drugs on 105 patients with locally advanced (Stage IIIa, IIIb) and
      metastatic (Stage IV) breast cancer. The survival rate of the Stage IIIb patients
      who showed a good histological response (Grade IIb< or =) to IAIC was 68.1% for 5
      years, and 62.4% for 10 years, respectively. This was in contrast to that of the
      patients classified as Stage IIIb who showed a poor histological response (Grade
      IIa> or =) to IAIC. On the other hand, there was no significant difference in the
      survival rates between the Stage IIIa and IV patients with good and poor
      histological responses to IAIC. However, the findings showed that a good
      histological response to IAIC reflected a prolonged survival while the Stage IIIb
      and IV patients acquired a "down clinical staging" by IAIC. These results
      strongly suggest that IAIC thus appears to be a useful modality in the
      multidisciplinary treatment of advanced breast cancer, especially for Stage IIIb
      patients.

PMID- 9607904
TI  - The effects of prostaglandin E1 and tyrosine kinase inhibitors on energy status
      and protein synthetic ability in hepatic ischemia-reperfusion injury.
AB  - The effects of prostaglandin E1 (PGE1) and tyrosine kinase inhibitors on hepatic
      energy status and protein synthesis in ischemic livers were studied using 31P
      magnetic resonance spectroscopy in a rat model. The continuous administration of
      PGE1 significantly increased the beta-adenosine triphosphate/inorganic phosphate
      (beta-ATP/Pi) ratio and hepatic protein synthesis rate (HPS) after ischemia
      reperfusion injury. Microscopic examination showed that the continuous
      administration of PGE1 inhibited the development of sinusoidal hemorrhage and
      edema. Thus, it was concluded that PGE1 has a beneficial effect on ischemia
      reperfusion injury in the liver. Pretreatment with tyrosine kinase inhibitor also
      increased the beta-ATP/Pi ratio; however, when tyrosine kinase inhibitor was
      injected before ischemia, the HPS became significantly reduced. Based on these
      data, the protective effect of tyrosine kinase inhibitor is unconvincing.

PMID- 9607905
TI  - Cardioprotective effect of succinate against ischemia/reperfusion injury.
AB  - We investigated the protective effects of succinate, which is a respiratory
      substrate and a potential antioxidant, on myocardial ischemia/reperfusion injury
      with the whole heart. Isolated rat hearts were loaded with 25-min normothermic
      global ischemia followed by 30-min reperfusion in a working heart model.
      Succinate administered either before reperfusion or added to the cardioplegic
      solution improved the postischemic cardiac function significantly. The hearts
      arrested with succinate-supplemented cardioplegic solution replenished high
      energy phosphates and maintained the total adenine nucleotides during the
      reperfusion period, whereas those arrested with succinate-nonsupplemented
      cardioplegic solution replenished the high-energy phosphates less, and also lost
      total adenine nucleotides during that period. We thus conclude that succinate
      administered before reperfusion may decrease the degree of mitochondrial damage
      during reperfusion and thereby reduce the amount of myocardial
      ischemia/reperfusion injury.

PMID- 9607906
TI  - Monitoring of acute allograft rejection by cytological, immunocytochemical, and
      immunohistochemical studies following rat small-bowel transplantation.
AB  - We investigated the role of graft luminal fluid cytology for immunological
      monitoring of rat small-bowel allograft recipients. Allogeneic transplantation
      from WKAM (RT1u) to Lewis recipients and syngeneic transplantation using Lewis
      (RT11) rats were carried out. Twenty centimeters of the proximal jejunum was
      transplanted as a Thiry-Vella loop. The luminal fluid on days 0, 3, and 6 was
      examined cytologically using Papanicolaou, periodic acid-Schiff, and Giemsa
      staining, and immunocytochemically with monoclonal antibodies for macrophages
      (ED1 and ED2). Full thickness biopsies of graft tissue were evaluated by both
      immunofluorescence (ED1 and ED2) and by standard histological methods. The
      cytological examination on day 6 revealed an increase in the number of
      enterocytes, lymphocytes, and neutrophils, the presence of bacteria, and the
      depletion of goblet cells in the allografts. Histologically, significant
      morphological changes of acute rejection were first seen on day 6.
      Immunofluorescence predicted the acute rejection of the allografts earlier than a
      histological examination by showing an increase in the number of ED1- and Ed2
      positive cells on day 3. Graft luminal fluid cytology and immunofluorescence
      analysis of ED1 and ED2 cells could thus be used to recognize early acute
      allograft rejection following small-bowel transplantation.

PMID- 9607907
TI  - Benign esophageal stricture caused by diffuse severe esophagitis presenting as
      ascending fibrosis: report of a case.
AB  - A 46-year-old Japanese man was referred to our hospital for treatment of an
      esophageal stricture. Esophageal cancer was suspected after detailed
      investigations, and a right transthoracic esophagectomy was performed. The
      resected specimen showed only nonspecific esophagitis with severe fibrous
      thickening in the submucosa, but no evidence of malignancy. Between 1906 and
      1993, only 19 similar cases of benign esophageal strictures with fibrous
      thickening, excluding congenital and iatrogenic strictures, have been reported in
      Japan. These lesions occurred in the middle to lower third of the esophagus in 15
      of 19 cases (78.9%), and 8 of the 19 patients (42.1%) were aged between 30 and 50
      years. The interval between onset and hospital admission was short, being less
      than 1 year in 8 of the 12 patients for whom this information was available. Our
      patient demonstrated a disorder resembling the diffuse severe esophagitis
      described by Roth in 1974.

PMID- 9607908
TI  - Hepatic infarction as a complication of gastric cancer surgery: report of four
      cases.
AB  - Four cases of patients who developed hepatic infarction caused by an operative
      injury to the hepatic circulation during gastric cancer surgery are reported
      herein. In two patients, the hepatic infarction resulted from accidental injury
      to the proper hepatic artery, and in the other two, it was possibly due to
      persistent pressure on the folded liver by a retractor during surgery. In the
      former two patients, the proper hepatic artery had been collapsed by the spread
      of enlarged metastatic lymph nodes before the onset of the arterial injury. In
      the latter two patients, postoperative laboratory data and computed tomography
      scanning revealed hepatic infarction even though preservation of the proper
      hepatic artery was confirmed by angiography. Elevated serum levels of hepatic
      enzymes released from the infarcted tissue recovered to the normal range within
      three weeks in all four patients. In conclusion, when an operative injury to the
      hepatic artery is encountered, the hepatoduodenal ligament should not be
      manipulated any more than necessary to preserve the collaterals, and the
      gallbladder should be removed to prevent necrotic perforation. Although close
      observation is mandatory, conservative therapy seems to be sufficient when an
      infarcted area is restricted to the lateral segment and a small part of the
      medial segment of the liver.

PMID- 9607909
TI  - Treatment of recurrent hepatocellular carcinoma by hepatectomy with right and
      middle hepatic vein reconstruction using total vascular exclusion with
      extracorporeal bypass and hypothermic hepatic perfusion: report of a case.
AB  - We report herein the case of a patient who had previously undergone a lateral
      segmentectomy for hepatocellular carcinoma (HCC) in whom recurrent HCC invading
      the trunk of the right and middle hepatic veins in a damaged liver was treated by
      reconstruction of both hepatic veins, using total vascular exclusion with
      extracorporeal bypass and hypothermic hepatic perfusion. Reconstruction was
      performed using a graft taken from the left external iliac vein and divided into
      two pieces. Hepatic ischemia lasted for 91 min during the procedure and the
      intrahepatic temperature, as monitored by inserting a needle-type thermometer,
      was decreased to 11 degrees C throughout the procedure. The peak levels of serum
      glutamic pyruvic transaminase, lactate dehydrogenase, and total bilirubin were
      363 IU/l, 1198 IU/ml, and 2.8 mg/dl, respectively, on postoperative day (POD) 2.
      The patient's postoperative course was uneventful except for mild, temporary
      swelling of the left leg. Postoperative computed tomography and magnetic
      resonance imaging examinations disclosed no obstruction of either graft, and the
      patient was discharged on POD 40.

PMID- 9607910
TI  - Diagnosis and management of metastatic gastrinoma by multimodality treatment
      including liver transplantation: report of a case.
AB  - Neuroendocrine tumors of the pancreas are being recognized with increasing
      frequency, not because the incidence has increased, but as a result of
      improvements in diagnostic tools such as radioimmunoassays for a variety of
      circulating peptides, and imaging methods that include positron emission
      tomography (PET) and immunoscintigraphy. Nevertheless, establishing the diagnosis
      of a neuroendocrine tumor is always a challenge to the clinician from both
      diagnostic and therapeutic perspectives. Liver transplantation as the ultimate
      therapeutic, or at least palliative, option for hepatic metastases has produced
      contradictory results over the past decade. We report herein the case of a 23
      year-old woman who, after being diagnosed with gastrinoma in 1989, underwent the
      complete therapeutic array including liver transplantation for hepatic metastases
      in 1991. Although an extrahepatic tumor recurred 2 years later, for which double
      chemotherapy with 5-FU and streptozotocin was given, she is currently leading a
      normal life with a full-time job. This case prompted a critical review of the
      current literature on diagnosis and medical and surgical treatment.

PMID- 9607911
TI  - Repeated percutaneous aspiration therapy prior to surgery for a pancreatic
      pseudocyst: report of a case.
AB  - We describe herein the case of a patient with a giant pancreatic pseudocyst which
      was first treated with repeated percutaneous aspiration therapy, then cured
      surgically by a Roux-en Y cystojejunostomy, 26 weeks after its formation. A 41
      year-old man developed alcohol-induced acute severe pancreatitis. Computed
      tomography (CT) performed 10 weeks after the onset revealed a giant cyst, 20 x 18
      x 7cm in size, arising from the body and tail of the pancreas and extending to
      the left loin. Endoscopic retrograde pancreatography (ERP) showed a normal main
      pancreatic duct without communication to the pseudocyst. As the asymptomatic
      pseudocyst, the wall of which was less than 2mm thick, had not resolved by 8
      weeks after its formation, percutaneous aspiration therapy was performed three
      times. The patient was treated as an outpatient without any complications. The
      cyst wall was subsequently confirmed to be mature enough for surgical management
      to be initiated, and a cystojejunostomy was safely performed. Thus, percutaneous
      aspiration therapy can enable the surgeon to observe maturation of the cyst wall
      for a long period in patients with a pancreatic pseudocyst.

PMID- 9607912
TI  - Cannulation-induced coronary artery dissection: successful management with
      circulatory assist devices and coronary bypass grafting.
AB  - A coronary artery dissection is a rare but well-known lethal complication
      associated with coronary perfusion. We herein report the case of a right coronary
      dissection that occurred after an aortic valve replacement. Coronary bypass
      grafting was successful after the establishment of mechanical biventricular
      support with an intra-aortic balloon pump and a right ventricular assist device.

PMID- 9607913
TI  - Genetic changes in primary colorectal cancer by comparative genomic
      hybridization.
AB  - Comparative genomic hybridization (CGH) is a powerful new technique for the
      molecular cytogenetic analysis of cancer. In this method, at first the cancer DNA
      and normal DNA are labeled with biotin and digoxigenin, respectively, and then
      the labeled DNAs are applied onto normal lymphocyte metaphase preparations in
      hybridization. After hybridization, they are stained with FITC and rhodamine,
      respectively, so chromosomal gains and losses in cancer are thus detected by
      using a green:red ratio. In this study, we analyzed the abnormal chromosomes in
      nine cases with human primary colon cancer. A gain in chromosomes 11p, 12q, 16p,
      20p, and 20q were observed, while a loss of 18q and 22q were discovered. CGH may
      thus provide us with important information for analyzing the genes in colon
      cancer.

PMID- 9607914
TI  - The role of DNA repair in somatic hypermutation of immunoglobulin genes.

PMID- 9607915
TI  - Hypermutation of immunoglobulin genes in memory B cells of DNA repair-deficient
      mice.
AB  - To investigate the possible involvement of DNA repair in the process of somatic
      hypermutation of rearranged immunoglobulin variable (V) region genes, we have
      analyzed the occurrence, frequency, distribution, and pattern of mutations in
      rearranged Vlambda1 light chain genes from naive and memory B cells in DNA repair
      deficient mutant mouse strains. Hypermutation was found unaffected in mice
      carrying mutations in either of the following DNA repair genes: xeroderma
      pigmentosum complementation group (XP)A and XPD, Cockayne syndrome
      complementation group B (CSB), mutS homologue 2 (MSH2), radiation sensitivity 54
      (RAD54), poly (ADP-ribose) polymerase (PARP), and 3-alkyladenine DNA-glycosylase
      (AAG). These results indicate that both subpathways of nucleotide excision
      repair, global genome repair, and transcription-coupled repair are not required
      for somatic hypermutation. This appears also to be true for mismatch repair,
      RAD54-dependent double-strand-break repair, and AAG-mediated base excision
      repair.

PMID- 9607916
TI  - Increased hypermutation at G and C nucleotides in immunoglobulin variable genes
      from mice deficient in the MSH2 mismatch repair protein.
AB  - Rearranged immunoglobulin variable genes are extensively mutated after
      stimulation of B lymphocytes by antigen. Mutations are likely generated by an
      error-prone DNA polymerase, and the mismatch repair pathway may process the
      mispairs. To examine the role of the MSH2 mismatch repair protein in
      hypermutation, Msh2-/- mice were immunized with oxazolone, and B cells were
      analyzed for mutation in their VkappaOx1 light chain genes. The frequency of
      mutation in the repair-deficient mice was similar to that in Msh2+/+ mice,
      showing that MSH2-dependent mismatch repair does not cause hypermutation.
      However, there was a striking bias for mutations to occur at germline G and C
      nucleotides. The results suggest that the hypermutation pathway frequently
      mutates G.C pairs, and a MSH2-dependent pathway preferentially corrects
      mismatches at G and C.

PMID- 9607917
TI  - Control of lytic function by mitogen-activated protein kinase/extracellular
      regulatory kinase 2 (ERK2) in a human natural killer cell line: identification of
      perforin and granzyme B mobilization by functional ERK2.
AB  - The signal pathways that control effector function in human natural killer (NK)
      cells are little known. In this study, we have identified the critical role of
      the mitogen-activated protein kinase (MAPK) pathway in NK lysis of tumor cells,
      and this pathway may involve the mobilization of granule components in NK cells
      upon interaction with sensitive tumor target cells. Evidence was provided by
      biological, biochemical, and gene transfection methods. NK cell binding to tumor
      cells for 5 min was sufficient to maximally activate MAPK/extracellular signal
      regulatory kinase 2 (ERK2), demonstrated by its tyrosine phosphorylation and by
      its ability to function as an efficient kinase for myelin basic protein. MAPK
      activation was achieved in NK cells only after contact with NK-sensitive but not
      NK-resistant target cells. In immunocytochemical studies, cytoplasmic perforin
      and granzyme B were both maximally redirected towards the tumor contact zone
      within 5 min of NK cell contact with tumor cells. A specific MAPK pathway
      inhibitor, PD098059, could block not only MAPK activation but also redistribution
      of perforin/granzyme B in NK cells, which occur upon target ligation. PD098059
      also interfered with NK lysis of tumor cells in a 5-h 51Cr-release assay, but had
      no ability to block NK cell proliferation. Transient transfection studies with
      wild-type and dominant-negative MAPK/ERK2 genes confirmed the importance of MAPK
      in NK cell lysis. These results document a pivotal role of MAPK in NK effector
      function, possibly by its control of movement of lytic granules, and clearly
      define MAPK involvement in a functional pathway unlinked to cell growth or
      differentiation.

PMID- 9607918
TI  - Early regeneration of thymic progenitors in rhesus macaques infected with simian
      immunodeficiency virus.
AB  - The thymus plays a critical role in the maturation and production of T
      lymphocytes and is a target of infection by human immunodeficiency virus (HIV)
      and the related simian immunodeficiency virus (SIV). Using the SIV/macaque model
      of AIDS, we examined the early effects of SIV on the thymus. We found that thymic
      infection by SIV resulted in increased apoptosis 7-14 d after infection, followed
      by depletion of thymocyte progenitors by day 21. A marked rebound in thymocyte
      progenitors occurred by day 50 and was accompanied by increased levels of cell
      proliferation in the thymus. Our results demonstrate a marked increase in thymic
      progenitor activity very early in the course of SIV infection, long before marked
      declines in peripheral CD4(+) T cell counts.

PMID- 9607919
TI  - Impaired anaphylactic responses with intact sensitivity to endotoxin in mice
      lacking a platelet-activating factor receptor.
AB  - Platelet-activating factor (PAF) is a potent phospholipid mediator with diverse
      biological activities in addition to its well-known ability to stimulate platelet
      aggregation. Pharmacologic studies had suggested a role for PAF in pregnancy,
      neuronal cell migration, anaphylaxis, and endotoxic shock. Here we show that
      disruption of the PAF receptor gene in mice caused a marked reduction in systemic
      anaphylactic symptoms. Unexpectedly, however, the PAF receptor-deficient mice
      developed normally, were fertile, and remained sensitive to bacterial endotoxin.
      These mutant mice clearly show that PAF plays a dominant role in eliciting
      anaphylaxis, but that it is not essential for reproduction, brain development, or
      endotoxic shock.

PMID- 9607920
TI  - T cell-dependent immune response in C1q-deficient mice: defective interferon
      gamma production by antigen-specific T cells.
AB  - The role of the classical complement pathway in humoral immune responses was
      investigated in gene-targeted C1q-deficient mice (C1qA-/-). Production of antigen
      specific immunoglobulin (Ig)G2a and IgG3 in primary and secondary responses to T
      cell-dependent antigen was significantly reduced, whereas IgM, IgG1, and IgG2b
      responses were similar in control and C1qA-/- mice. Despite abnormal humoral
      responses, B cells from C1qA-/- mice proliferated normally to a number of stimuli
      in vitro. Immune complex localization to follicular dendritic cells within
      splenic follicles was lacking in C1qA-/- mice. The precursor frequency of antigen
      specific T cells was similar in C1qA-/- and wild-type mice. However, analysis of
      cytokine production by primed T cells in response to keyhole limpet hemocyanin
      revealed a significant reduction in interferon-gamma production in C1qA-/- mice
      compared with control mice, whereas interleukin 4 secretion was equivalent. These
      data suggest that the classical pathway of complement may influence the cytokine
      profile of antigen-specific T lymphocytes and the subsequent immune response.

PMID- 9607921
TI  - The serine proteinase inhibitor (serpin) plasminogen activation inhibitor type 2
      protects against viral cytopathic effects by constitutive interferon alpha/beta
      priming.
AB  - The serine proteinase inhibitor (serpin) plasminogen activator inhibitor type 2
      (PAI-2) is well characterized as an inhibitor of extracellular urokinase-type
      plasminogen activator. Here we show that intracellular, but not extracellular,
      PAI-2 protected cells from the rapid cytopathic effects of alphavirus infection.
      This protection did not appear to be related to an effect on apoptosis but was
      associated with a PAI-2-mediated induction of constitutive low-level interferon
      (IFN)-alpha/beta production and IFN-stimulated gene factor 3 (ISGF3) activation,
      which primed the cells for rapid induction of antiviral genes. This primed
      phenotype was associated with a rapid development of resistance to infection by
      the PAI-2 transfected cells and the establishment of a persistent productive
      infection. PAI-2 was also induced in macrophages in response to viral RNA
      suggesting that PAI-2 is a virus response gene. These observations, together with
      the recently demonstrated PAI-2-mediated inhibition of tumor necrosis factor
      alpha induced apoptosis, (a) illustrate that PAI-2 has an additional and distinct
      function as an intracellular regulator of signal transduction pathway(s) and (b)
      demonstrate a novel activity for a eukaryotic serpin.

PMID- 9607922
TI  - An alternate pathway for T cell development supported by the bone marrow
      microenvironment: recapitulation of thymic maturation.
AB  - In the principal pathway of alpha/beta T cell maturation, T cell precursors from
      the bone marrow migrate to the thymus and proceed through several well
      characterized developmental stages into mature CD4+ and CD8+ T cells. This study
      demonstrates an alternative pathway in which the bone marrow microenvironment
      also supports the differentiation of T cell precursors into CD4+ and CD8+ T
      cells. The marrow pathway recapitulates developmental stages of thymic maturation
      including a CD4+CD8+ intermediary cell and positive and negative selection, and
      is strongly inhibited by the presence of mature T cells. The contribution of the
      marrow pathway in vivo requires further study in mice with normal and deficient
      thymic or immune function.

PMID- 9607923
TI  - Spontaneous development of plasmacytoid tumors in mice with defective Fas-Fas
      ligand interactions.
AB  - B cell malignancies arise with increased frequency in aging individuals and in
      patients with genetic or acquired immunodeficiency (e.g., AIDS) or autoimmune
      diseases. The mechanisms of lymphomagenesis in these individuals are poorly
      understood. In this report we investigated the possibility that mutations at the
      Fas (lpr) and Fasl (gld) loci, which prevent Fas-mediated apoptosis and cause an
      early onset benign lymphoid hyperplasia and autoimmunity, also predispose mice to
      malignant lymphomas later in life. Up to 6 mo of age, hyperplasia in lpr and gld
      mice results from the predominant accumulation of polyclonal T cell subsets and
      smaller numbers of polyclonal B cells and plasma cells. Here, we examined C3H
      lpr, C3H-gld, and BALB-gld mice 6-15 mo of age for the emergence of clonal T and
      B cell populations and found that a significant proportion of aging mice
      exclusively developed B cell malignancies with many of the hallmarks of
      immunodeficiency-associated B lymphomas. By 1 yr of age, approximately 60% of
      BALB-gld and 30% of C3H-gld mice had monoclonal B cell populations that grew and
      metastasized in scid recipients but in most cases were rejected by
      immunocompetent mice. The tumors developed in a milieu greatly enriched for
      plasma cells, CD23- B cells and immunodeficient memory T cells and variably
      depleted of B220+ DN T cells. Growth factor-independent cell lines were
      established from five of the tumors. The majority of the tumors were CD23- and
      IgH isotype switched and a high proportion was CD5+ and dull Mac-1+. Considering
      their Ig secretion and morphology in vivo, most tumors were classified as
      malignant plasmacytoid lymphomas. The delayed development of the gld tumors
      indicated that genetic defects in addition to the Fas/Fasl mutations were
      necessary for malignant transformation. Interestingly, none of the tumors showed
      changes in the genomic organization of c-Myc but many had one or more somatically
      acquired MuLV proviral integrations that were transmitted in scid passages and
      cell lines. Therefore, insertional mutagenesis may be a mechanism for
      transformation in gld B cells. Our panel of in vivo passaged and in vitro adapted
      gld lymphomas will be a valuable tool for the future identification of genetic
      abnormalities associated with B cell transformation in aging and autoimmune mice.

PMID- 9607924
TI  - The role of the thymus and recent thymic migrants in the maintenance of the adult
      peripheral lymphocyte pool.
AB  - The thymus is essential for the initial seeding of T cells to the periphery, but
      its role in maintaining the adult T cell pool remains poorly defined. We
      investigated whether changes to the rate of T cell export could form part of the
      mechanism(s) controlling the homeostatic regulation of the size and composition
      of the peripheral T cell pool. Using neonatal thymi grafted under the kidney
      capsule, we found that irrespective of whether the pool was oversupplied (by
      thymic grafts) or undersupplied (due to neonatal thymectomy), the thymic export
      rate was constant from both the host and graft thymus, and the periphery remained
      constant in size. Recent thymic emigrants (RTE) were also tracked to determine
      the extent of their acceptance into the T cell pool of a normal mouse. As a
      population, RTE are phenotypically mature, but were distinct from resident T
      cells in the periphery, being released in a CD4/CD8 ratio approximately twice
      that of established peripheral T cells. This export ratio is similar to that of T
      cells in the mature thymic compartment, but soon after entry into the periphery,
      the ratio falls, indicating separate thymic and peripheral regulation of the
      CD4/CD8 ratio. RTE may also be preferentially incorporated into the periphery,
      causing displacement of resident T cells, thus maintaining the size of the
      peripheral pool. Although not vital for the maintenance of a functional T cell
      pool, the acceptance of RTE in a "full" peripheral pool would ensure that the T
      cell receptor repertoire is kept diverse and that the T cell population
      encompasses a broad range of naive as well as memory T cells.

PMID- 9607925
TI  - CD28-independent, TRAF2-dependent costimulation of resting T cells by 4-1BB
      ligand.
AB  - 4-1BB ligand (4-1BBL) is a member of the tumor necrosis factor (TNF) family
      expressed on activated antigen-presenting cells. Its receptor, 4-1BB, is a member
      of the TNF receptor family expressed on activated CD4 and CD8 T cells. We have
      produced a soluble form of 4-1BBL using the baculovirus expression system. When
      coimmobilized on plastic with anti-CD3, soluble 4-1BBL induces interleukin (IL)-2
      production by resting CD28+ or CD28- T cells, indicating that 4-1BBL can function
      independently of other cell surface molecules, including CD28, in costimulation
      of resting T cell activation. At low concentrations of anti-CD3, 4-1BBL is
      inferior to anti-CD28 in T cell activation. However, when 4-1BB ligand is
      provided together with strong TCR signals, then 4-1BBL and anti-CD28 are equally
      potent in stimulation of IL-2 production by resting T cells. We find that TNF
      receptor-associated factor (TRAF)1 or TRAF2 associate with a glutathione S
      transferase-4-1BB cytoplasmic domain fusion protein in vitro. In T cells, we find
      that association of TRAF1 and TRAF2 with 4-1BB requires 4-1BB cross-linking. In
      support of a functional role for TRAF2 in 4-1BB signaling, we find that resting T
      cells isolated from TRAF2-deficient mice or from mice expressing a dominant
      negative form of TRAF2 fail to augment IL-2 production in response to soluble 4
      1BBL. Thus 4-1BB, via the TRAF2 molecule, can provide CD28-independent
      costimulatory signals to resting T cells.

PMID- 9607926
TI  - Disruption of lymphocyte function and signaling in CD45-associated protein-null
      mice.
AB  - CD45-AP specifically associates with CD45, a protein tyrosine phosphatase
      essential for lymphocyte differentiation and antigen receptor-mediated signal
      transduction. CD45 is thought to mediate antigen receptor signaling by
      dephosphorylating regulatory tyrosine residues on Src family protein tyrosine
      kinases such as Lck. However, the mechanism for regulating CD45 protein tyrosine
      phosphatase activity remains unclear. CD45-AP-null mice were created to examine
      the role of CD45-AP in CD45-mediated signal transduction. T and B lymphocytes
      showed reduced proliferation in response to antigen receptor stimulation. Both
      mixed leukocyte reaction and cytotoxic T lymphocyte functions of T cells were
      also markedly decreased in CD45-AP-null mice. Interestingly, the interaction
      between CD45 and Lck was significantly reduced in CD45-AP-null T cells,
      indicating that CD45-AP directly or indirectly mediates the interaction of CD45
      with Lck. Our data indicate that CD45-AP is required for normal antigen receptor
      signaling and function in lymphocytes.

PMID- 9607927
TI  - Quantitative analysis of the T cell repertoire selected by a single peptide-major
      histocompatibility complex.
AB  - The positive selection of CD4+ T cells requires the expression of major
      histocompatibility complex (MHC) class II molecules in the thymus, but the role
      of self-peptides complexed to class II molecules is still a matter of debate.
      Recently, it was observed that transgenic mice expressing a single peptide-MHC
      class II complex positively select significant numbers of diverse CD4+ T cells in
      the thymus. However, the number of selected T cell specificities has not been
      evaluated so far. Here, we have sequenced 700 junctional complementarity
      determining regions 3 (CDR3) from T cell receptors (TCRs) carrying Vbeta11
      Jbeta1.1 or Vbeta12-Jbeta1.1 rearrangements. We found that a single peptide-MHC
      class II complex positively selects at least 10(5) different Vbeta
      rearrangements. Our data yield a first evaluation of the size of the T cell
      repertoire. In addition, they provide evidence that the single Ealpha52-68-I-Ab
      complex skews the amino acid frequency in the TCR CDR3 loop of positively
      selected T cells. A detailed analysis of CDR3 sequences indicates that a fraction
      of the beta chain repertoire bears the imprint of the selecting self-peptide.

PMID- 9607928
TI  - Thalidomide costimulates primary human T lymphocytes, preferentially inducing
      proliferation, cytokine production, and cytotoxic responses in the CD8+ subset.
AB  - The efficacy of thalidomide (alpha-phthalimido-glutarimide) therapy in leprosy
      patients with erythema nodosum leprosum is thought to be due to inhibition of
      tumor necrosis factor alpha. In other diseases reported to respond to
      thalidomide, the mechanism of action of the drug is unclear. We show that
      thalidomide is a potent costimulator of primary human T cells in vitro,
      synergizing with stimulation via the T cell receptor complex to increase
      interleukin 2-mediated T cell proliferation and interferon gamma production. The
      costimulatory effect is greater on the CD8+ than the CD4+ T cell subset. The drug
      also increases the primary CD8+ cytotoxic T cell response induced by allogeneic
      dendritic cells in the absence of CD4+ T cells. Therefore, human T cell
      costimulation can be achieved pharmacologically with thalidomide, and
      preferentially in the CD8+ T cell subset.

PMID- 9607929
TI  - Nf1 regulates hematopoietic progenitor cell growth and ras signaling in response
      to multiple cytokines.
AB  - Neurofibromin, the protein encoded by the NF1 tumor-suppressor gene, negatively
      regulates the output of p21(ras) (Ras) proteins by accelerating the hydrolysis of
      active Ras-guanosine triphosphate to inactive Ras-guanosine diphosphate. Children
      with neurofibromatosis type 1 (NF1) are predisposed to juvenile chronic
      myelogenous leukemia (JCML) and other malignant myeloid disorders, and
      heterozygous Nf1 knockout mice spontaneously develop a myeloid disorder that
      resembles JCML. Both human and murine leukemias show loss of the normal allele.
      JCML cells and Nf1-/- hematopoietic cells isolated from fetal livers selectively
      form abnormally high numbers of colonies derived from granulocyte-macrophage
      progenitors in cultures supplemented with low concentrations of granulocyte
      macrophage colony stimulating factor (GM-CSF). Taken together, these data suggest
      that neurofibromin is required to downregulate Ras activation in myeloid cells
      exposed to GM-CSF. We have investigated the growth and proliferation of purified
      populations of hematopoietic progenitor cells isolated from Nf1 knockout mice in
      response to the cytokines interleukin (IL)-3 and stem cell factor (SCF), as well
      as to GM-CSF. We found abnormal proliferation of both immature and lineage
      restricted progenitor populations, and we observed increased synergy between SCF
      and either IL-3 or GM-CSF in Nf1-/- progenitors. Nf1-/- fetal livers also showed
      an absolute increase in the numbers of immature progenitors. We further
      demonstrate constitutive activation of the Ras-Raf-MAP (mitogen-activated
      protein) kinase signaling pathway in primary c-kit+ Nf1-/- progenitors and
      hyperactivation of MAP kinase after growth factor stimulation. The results of
      these experiments in primary hematopoietic cells implicate Nf1 as playing a
      central role in regulating the proliferation and survival of primitive and
      lineage-restricted myeloid progenitors in response to multiple cytokines by
      modulating Ras output.

PMID- 9607931
TI  - Eliminating a region of respiratory syncytial virus attachment protein allows
      induction of protective immunity without vaccine-enhanced lung eosinophilia.
AB  - In a murine model of respiratory syncytial virus disease, prior sensitization to
      the attachment glycoprotein (G) leads to pulmonary eosinophilia and enhanced
      illness. Three different approaches were taken to dissect the region of G
      responsible for enhanced disease and protection against challenge. First, mutant
      viruses, containing frameshifts that altered the COOH terminus of the G protein,
      were used to challenge mice sensitized by scarification with recombinant vaccinia
      virus (rVV) expressing wild-type G. Second, cDNA expressing these mutated G
      proteins were expressed by rVV and used to vaccinate mice before challenge with
      wild-type respiratory syncytial virus (RSV). These studies identified residues
      193-205 to be responsible for G-induced weight loss and lung eosinophilia and
      showed that this region was not was not necessary for induction of protective
      immunity. Third, mice were sensitized using an rVV that expressed only amino
      acids 124-203 of the G protein. Upon RSV challenge, mice sensitized with this rVV
      developed enhanced weight loss and eosinophilia. This is the first time that a
      region within RSV (amino acids 193-203) has been shown to be responsible for
      induction of lung eosinophilia and disease enhancement. Moreover, we now show
      that it is possible to induce protective immunity with an altered G protein
      without inducing a pathological response.

PMID- 9607930
TI  - Aplastic anemia rescued by exhaustion of cytokine-secreting CD8+ T cells in
      persistent infection with lymphocytic choriomeningitis virus.
AB  - Aplastic anemia may be associated with persistent viral infections that result
      from failure of the immune system to control virus. To evaluate the effects on
      hematopoiesis exerted by sustained viral replication in the presence of activated
      T cells, blood values and bone marrow (BM) function were analyzed in chronic
      infection with lymphocytic choriomeningitis virus (LCMV) in perforin-deficient
      (P0/0) mice. These mice exhibit a vigorous T cell response, but are unable to
      eliminate the virus. Within 14 d after infection, a progressive pancytopenia
      developed that eventually was lethal due to agranulocytosis and thrombocytopenia
      correlating with an increasing loss of morphologically differentiated,
      pluripotent, and committed progenitors in the BM. This hematopoietic disease
      caused by a noncytopathic chronic virus infection was prevented by depletion of
      CD8+, but not of CD4+, T cells and accelerated by increasing the frequency of
      LCMV-specific CD8+ T cells in T cell receptor (TCR) transgenic (tg) mice. LCMV
      and CD8+ T cells were found only transiently in the BM of infected wild-type
      mice. In contrast, increased numbers of CD8+ T cells and LCMV persisted at high
      levels in antigen-presenting cells of infected P0/0 and P0/0 x TCR tg mice. No
      cognate interaction between the TCR and hematopoietic progenitors presenting
      either LCMV-derived or self-antigens on the major histocompatibility complex was
      found, but damage to hematopoiesis was due to excessive secretion and action of
      tumor necrosis factor (TNF)/lymphotoxin (LT)-alpha and interferon (IFN)-gamma
      produced by CD8+ T cells. This was studied in double-knockout mice that were
      genetically deficient in perforin and TNF receptor type 1. Compared with P0/0
      mice, these mice had identical T cell compartments and T cell responses to LCMV,
      yet they survived LCMV infection and became life-long virus carriers. The numbers
      of hematopoietic precursors in the BM were increased compared with P0/0 mice
      after LCMV infection, although transient blood disease was still noticed. This
      residual disease activity was found to depend on IFN-gamma-producing LCMV
      specific T cells and the time point of hematopoietic recovery paralleled
      disappearance of these virus-specific, IFN-gamma-producing CD8+ T cells. Thus, in
      the absence of IFN-gamma and/or TNF/LT-alpha, exhaustion of virus-specific T
      cells was not hampered.

PMID- 9607932
TI  - Inactivation and secondary structure in the D4/S4-5 region of the SkM1 sodium
      channel.
AB  - The D4/S4-5 interhelical region plays a role in sodium channel fast inactivation.
      Examination of S4-5 primary structure in all domains suggests a possible
      amphipathic helical conformation in which a conserved group of small hydrophobic
      residues occupies one contiguous surface with a more variable complement of
      nonpolar and polar residues on the opposite face. We evaluated this potential
      structure by replacing each residue in D4/S4-5 of the rat SkM1 skeletal muscle
      sodium channel with substitutions having different side chain properties. Of the
      63 mutations analyzed, 44 produced functional channels. P1473 was intolerant of
      substitutions. Nonpolar substitutions in the conserved hydrophobic region were
      functionally similar to wild type, while charged mutations in this region before
      P1473 were nonfunctional. Charged mutations at F1466, M1469, M1470, and A1474,
      located on the opposite surface of the predicted helix, produced functional
      channels with pronounced slowing of inactivation, shifted voltage dependence of
      steady-state inactivation, and increased rate of recovery from inactivation. The
      substituted-cysteine-accessibility method was used to probe accessibility at each
      position. Residues L1465, F1466, A1467, M1469, M1470, L1472, A1474, and F1476C
      were easily accessible for modification by sulfhydryl reagents; L1464, L1468,
      S1471, and L1475 were not accessible within the time frame of our measurements.
      Molecular dynamics simulations of residues A1458 to N1477 were then used to
      explore energetically favorable local structures. Based on mutagenesis,
      substituted-cysteine-accessibility method, and modeling results, we suggest a
      secondary structure for the D4/S4-5 region in which the peptide chain is alpha
      helical proximal to P1473, bends at this residue, and may continue beyond this
      point as a random coil. In this configuration, the entire resultant loop is
      amphipathic; four residues on one surface could form part of the binding site for
      the inactivation particle.

PMID- 9607933
TI  - State-dependent accessibility and electrostatic potential in the channel of the
      acetylcholine receptor. Inferences from rates of reaction of thiosulfonates with
      substituted cysteines in the M2 segment of the alpha subunit.
AB  - Ion channel function depends on the chemical and physical properties and spatial
      arrangement of the residues that line the channel lumen and on the electrostatic
      potential within the lumen. We have used small, sulfhydryl-specific thiosulfonate
      reagents, both positively charged and neutral, to probe the environment within
      the acetylcholine (ACh) receptor channel. Rate constants were determined for
      their reactions with cysteines substituted for nine exposed residues in the
      second membrane-spanning segment (M2) of the alpha subunit. The largest rate
      constants, both in the presence and absence of ACh, were for the reactions with
      the cysteine substituted for alpha Thr244, near the intracellular end of the
      channel. In the open state of the channel, but not in the closed state, the rate
      constants for the reactions of the charged reagents with several substituted
      cysteines depended on the transmembrane electrostatic potential, and the
      electrical distance of these cysteines increased from the extracellular to the
      intracellular end of M2. Even at zero transmembrane potential, the ratios of the
      rate constants for the reactions of three positively charged reagents with alpha
      T244C, alpha L251C, and alpha L258C to the rate constant for the reaction of an
      uncharged reagent were much greater in the open than in the closed state. This
      dependence of the rate constants on reagent charge is consistent with an
      intrinsic electrostatic potential in the channel that is considerably more
      negative in the open state than in the closed state. The effects of ACh on the
      rate constants for the reactions of substituted Cys along the length of alpha M2,
      on the dependence of the rate constants on the transmembrane potential, and on
      the intrinsic potential support a location of a gate more intracellular than
      alpha Thr244.

PMID- 9607934
TI  - Functional reconstitution of a prokaryotic K+ channel.
AB  - SliK, a K+ channel encoded by the Streptomyces KcsA gene, was expressed,
      purified, and reconstituted in liposomes. A concentrative 86Rb+ flux assay was
      used to assess the ion transport properties of SliK. SliK-mediated ionic flux
      shows strong selectivity for K+ over Na+ and is inhibited by micromolar
      concentrations of Ba2+, mirroring the basic permeation characteristic of
      eukaryotic K+ channels studied by electrophysiological methods. 86Rb+ uptake
      kinetics and equilibrium measurements also demonstrate that the purified protein
      is fully active.

PMID- 9607935
TI  - Kinetic structure of large-conductance Ca2+-activated K+ channels suggests that
      the gating includes transitions through intermediate or secondary states. A
      mechanism for flickers.
AB  - Mechanisms for the Ca2+-dependent gating of single large-conductance Ca2+
      activated K+ channels from cultured rat skeletal muscle were developed using two
      dimensional analysis of single-channel currents recorded with the patch clamp
      technique. To extract and display the essential kinetic information, the kinetic
      structure, from the single channel currents, adjacent open and closed intervals
      were binned as pairs and plotted as two-dimensional dwell-time distributions, and
      the excesses and deficits of the interval pairs over that expected for
      independent pairing were plotted as dependency plots. The basic features of the
      kinetic structure were generally the same among single large-conductance Ca2+
      activated K+ channels, but channel-specific differences were readily apparent,
      suggesting heterogeneities in the gating. Simple gating schemes drawn from the
      Monod- Wyman-Changeux (MWC) model for allosteric proteins could approximate the
      basic features of the Ca2+ dependence of the kinetic structure. However,
      consistent differences between the observed and predicted dependency plots
      suggested that additional brief lifetime closed states not included in MWC-type
      models were involved in the gating. Adding these additional brief closed states
      to the MWC-type models, either beyond the activation pathway (secondary closed
      states) or within the activation pathway (intermediate closed states), improved
      the description of the Ca2+ dependence of the kinetic structure. Secondary closed
      states are consistent with the closing of secondary gates or channel block.
      Intermediate closed states are consistent with mechanisms in which the channel
      activates by passing through a series of intermediate conformations between the
      more stable open and closed states. It is the added secondary or intermediate
      closed states that give rise to the majority of the brief closings (flickers) in
      the gating.

PMID- 9607937
TI  - Idiosyncratic gating of HERG-like K+ channels in microglia.
AB  - A simple kinetic model is presented to explain the gating of a HERG-like voltage
      gated K+ conductance described in the accompanying paper (Zhou, W., F.S.
      Cayabyab, P.S. Pennefather, L.C. Schlichter, and T.E. DeCoursey. 1998. J. Gen.
      Physiol. 111:781-794). The model proposes two kinetically distinct closing
      pathways, a rapid one favored by depolarization (deactivation) and a slow one
      favored by hyperpolarization (inactivation). The overlap of these two processes
      leads to a window current between -50 and +20 mV with a peak at -36 mV of
      approximately 12% maximal conductance. The near absence of depolarization
      activated outward current in microglia, compared with HERG channels expressed in
      oocytes or cardiac myocytes, can be explained if activation is shifted negatively
      in microglia. As seen with experimental data, availability predicted by the model
      was more steeply voltage dependent, and the midpoint more positive when
      determined by making the holding potential progressively more positive at
      intervals of 20 s (starting at -120 mV), rather than progressively more negative
      (starting at 40 mV). In the model, this hysteresis was generated by postulating
      slow and ultra-slow components of inactivation. The ultra-slow component takes
      minutes to equilibrate at -40 mV but is steeply voltage dependent, leading to
      protocol-dependent modulation of the HERG-like current. The data suggest that
      "deactivation" and "inactivation" are coupled through the open state. This is
      particularly evident in isotonic Cs+, where a delayed and transient outward
      current develops on depolarization with a decay time constant more voltage
      dependent and slower than the deactivation process observed at the same potential
      after a brief hyperpolarization.

PMID- 9607936
TI  - HERG-like K+ channels in microglia.
AB  - A voltage-gated K+ conductance resembling that of the human ether-a-go-go-related
      gene product (HERG) was studied using whole-cell voltage-clamp recording, and
      found to be the predominant conductance at hyperpolarized potentials in a cell
      line (MLS-9) derived from primary cultures of rat microglia. Its behavior
      differed markedly from the classical inward rectifier K+ currents described
      previously in microglia, but closely resembled HERG currents in cardiac muscle
      and neuronal tissue. The HERG-like channels opened rapidly on hyperpolarization
      from 0 mV, and then decayed slowly into an absorbing closed state. The peak K+
      conductance-voltage relation was half maximal at -59 mV with a slope factor of
      18.6 mV. Availability, assessed by a hyperpolarizing test pulse from different
      holding potentials, was more steeply voltage dependent, and the midpoint was more
      positive (-14 vs. -39 mV) when determined by making the holding potential
      progressively more positive than more negative. The origin of this hysteresis is
      explored in a companion paper (Pennefather, P.S., W. Zhou, and T.E. DeCoursey.
      1998. J. Gen. Physiol. 111:795-805). The pharmacological profile of the current
      differed from classical inward rectifier but closely resembled HERG. Block by Cs+
      or Ba2+ occurred only at millimolar concentrations, La3+ blocked with Ki =
      approximately 40 microM, and the HERG-selective blocker, E-4031, blocked with Ki
      = 37 nM. Implications of the presence of HERG-like K+ channels for the ontogeny
      of microglia are discussed.

PMID- 9607938
TI  - Inactivation of gating currents of L-type calcium channels. Specific role of the
      alpha 2 delta subunit.
AB  - In studies of gating currents of rabbit cardiac Ca channels expressed as alpha
      1C/beta 2a or alpha 1C/beta 2a/alpha 2 delta subunit combinations in tsA201
      cells, we found that long-lasting depolarization shifted the distribution of
      mobile charge to very negative potentials. The phenomenon has been termed charge
      interconversion in native skeletal muscle (Brum, G., and E. Rios. 1987. J.
      Physiol. (Camb.). 387:489-517) and cardiac Ca channels (Shirokov, R., R. Levis,
      N. Shirokova, and E. Rios. 1992. J. Gen. Physiol. 99:863-895). Charge 1 (voltage
      of half-maximal transfer, V1/2 approximately 0 mV) gates noninactivated channels,
      while charge 2 (V1/2 approximately -90 mV) is generated in inactivated channels.
      In alpha 1C/beta 2a cells, the available charge 1 decreased upon inactivating
      depolarization with a time constant tau approximately 8, while the available
      charge 2 decreased upon recovery from inactivation (at -200 mV) with tau
      approximately 0.3 s. These processes therefore are much slower than charge
      movement, which takes <50 ms. This separation between the time scale of
      measurable charge movement and that of changes in their availability, which was
      even wider in the presence of alpha 2 delta, implies that charges 1 and 2
      originate from separate channel modes. Because clear modal separation
      characterizes slow (C-type) inactivation of Na and K channels, this observation
      establishes the nature of voltage-dependent inactivation of L-type Ca channels as
      slow or C-type. The presence of the alpha 2 delta subunit did not change the V1/2
      of charge 2, but sped up the reduction of charge 1 upon inactivation at 40 mV (to
      tau approximately 2 s), while slowing the reduction of charge 2 upon recovery
      (tau approximately 2 s). The observations were well simulated with a model that
      describes activation as continuous electrodiffusion (Levitt, D. 1989. Biophys. J.
      55:489-498) and inactivation as discrete modal change. The effects of alpha 2
      delta are reproduced assuming that the subunit lowers the free energy of the
      inactivated mode.

PMID- 9607939
TI  - Electrophysiological characterization of the rat epithelial Na+ channel (rENaC)
      expressed in MDCK cells. Effects of Na+ and Ca2+.
AB  - The epithelial Na+ channel (ENaC), composed of three subunits (alpha, beta, and
      gamma), is expressed in several epithelia and plays a critical role in salt and
      water balance and in the regulation of blood pressure. Little is known, however,
      about the electrophysiological properties of this cloned channel when expressed
      in epithelial cells. Using whole-cell and single channel current recording
      techniques, we have now characterized the rat alpha beta gamma ENaC (rENaC)
      stably transfected and expressed in Madin-Darby canine kidney (MDCK) cells. Under
      whole-cell patch-clamp configuration, the alpha beta gamma rENaC-expressing MDCK
      cells exhibited greater whole cell Na+ current at -143 mV (-1,466.2 +/- 297.5 pA)
      than did untransfected cells (-47.6 +/- 10.7 pA). This conductance was completely
      and reversibly inhibited by 10 microM amiloride, with a Ki of 20 nM at a membrane
      potential of -103 mV; the amiloride inhibition was slightly voltage dependent.
      Amiloride-sensitive whole-cell current of MDCK cells expressing alpha beta or
      alpha gamma subunits alone was -115.2 +/- 41.4 pA and -52.1 +/- 24.5 pA at -143
      mV, respectively, similar to the whole-cell Na+ current of untransfected cells.
      Relaxation analysis of the amiloride-sensitive current after voltage steps
      suggested that the channels were activated by membrane hyperpolarization. Ion
      selectivity sequence of the Na+ conductance was Li+ > Na+ >> K+ = N-methyl-D
      glucamine+ (NMDG+). Using excised outside-out patches, amiloride-sensitive single
      channel conductance, likely responsible for the macroscopic Na+ channel current,
      was found to be approximately 5 and 8 pS when Na+ and Li+ were used as a charge
      carrier, respectively. K+ conductance through the channel was undetectable. The
      channel activity, defined as a product of the number of active channel (n) and
      open probability (Po), was increased by membrane hyperpolarization. Both whole
      cell Na+ current and conductance were saturated with increased extracellular Na+
      concentrations, which likely resulted from saturation of the single channel
      conductance. The channel activity (nPo) was significantly decreased when
      cytosolic Na+ concentration was increased from 0 to 50 mM in inside-out patches.
      Whole-cell Na+ conductance (with Li+ as a charge carrier) was inhibited by the
      addition of ionomycin (microM) and Ca2+ (1 mM) to the bath. Dialysis of the cells
      with a pipette solution containing 1 microM Ca2+ caused a biphasic inhibition,
      with time constants of 1.7 +/- 0.3 min (n = 3) and 128.4 +/- 33.4 min (n = 3). An
      increase in cytosolic Ca2+ concentration from <1 nM to 1 microM was accompanied
      by a decrease in channel activity. Increasing cytosolic Ca2+ to 10 microM
      exhibited a pronounced inhibitory effect. Single channel conductance, however,
      was unchanged by increasing free Ca2+ concentrations from <1 nM to 10 microM.
      Collectively, these results provide the first characterization of rENaC
      heterologously expressed in a mammalian epithelial cell line, and provide
      evidence for channel regulation by cytosolic Na+ and Ca2+.

PMID- 9607940
TI  - Single-channel properties of inositol (1,4,5)-trisphosphate receptor
      heterologously expressed in HEK-293 cells.
AB  - The inositol (1,4,5)-trisphosphate receptor (InsP3R) mediates Ca2+ release from
      intracellular stores in response to generation of second messenger InsP3. InsP3R
      was biochemically purified and cloned, and functional properties of native InsP3
      gated Ca2+ channels were extensively studied. However, further studies of InsP3R
      are obstructed by the lack of a convenient functional assay of expressed InsP3R
      activity. To establish a functional assay of recombinant InsP3R activity,
      transient heterologous expression of neuronal rat InsP3R cDNA (InsP3R-I, SI- SII+
      splice variant) in HEK-293 cells was combined with the planar lipid bilayer
      reconstitution experiments. Recombinant InsP3R retained specific InsP3 binding
      properties (Kd = 60 nM InsP3) and were specifically recognized by anti-InsP3R-I
      rabbit polyclonal antibody. Density of expressed InsP3R-I was at least 20-fold
      above endogenous InsP3R background and only 2-3-fold lower than InsP3R density in
      rat cerebellar microsomes. When incorporated into planar lipid bilayers, the
      recombinant InsP3R formed a functional InsP3-gated Ca2+ channel with 80 pS
      conductance using 50 mM Ba2+ as a current carrier. Mean open time of recombinant
      InsP3-gated channels was 3.0 ms; closed dwell time distribution was double
      exponential and characterized by short (18 ms) and long (130 ms) time constants.
      Overall, gating and conductance properties of recombinant neuronal rat InsP3R-I
      were very similar to properties of native rat cerebellar InsP3R recorded in
      identical experimental conditions. Recombinant InsP3R also retained bell-shaped
      dependence on cytosolic Ca2+ concentration and allosteric modulation by ATP,
      similar to native cerebellar InsP3R. The following conclusions are drawn from
      these results. (a) Rat neuronal InsP3R-I cDNA encodes a protein that is either
      sufficient to produce InsP3-gated channel with functional properties identical to
      the properties of native rat cerebellar InsP3R, or it is able to form a
      functional InsP3-gated channel by forming a complex with proteins endogenously
      expressed in HEK-293 cells. (b) Successful functional expression of InsP3R in a
      heterologous expression system provides an opportunity for future detailed
      structure-function characterization of this vital protein.

PMID- 9607942
TI  - Current perspectives on pain upon injection of drugs.
AB  - A limitation in the administration of parenteral products is the pain caused upon
      injection. Injection site pain has been predominately associated with
      intravenous, intramuscular, and subcutaneous administration. It becomes important
      for the formulation scientist to have a basic understanding of the physiology
      underlying the pain process, as well as the pharmaceutical factors associated
      with injection site pain. Initially, this review will provide the reader with a
      primer on the mediation of pain in the periphery and a compilation of those drugs
      that have been associated with pain on injection. In addition, this review will
      present important considerations and general formulation approaches or methods
      that have been used to overcome pain on injection. Finally, a brief overview of
      the various experimental systems used to investigate injection site pain is
      discussed.

PMID- 9607943
TI  - Stability of peptide-condensed plasmid DNA formulations.
AB  - Low molecular weight homogeneous peptides were used to form peptide/DNA
      condensates. A peptide possessing 18 lysines was found to protect plasmid DNA
      from serum endonuclease and sonicative-induced degradation whereas a shorter
      peptide possessing 8 lysines dissociated in 0.1 M sodium chloride and failed to
      protect DNA from enzymatic degradation. Peptide-condensed DNA showed no change in
      the ratio of supercoiled to circular DNA following 100 W sonication for up to 60
      s and was able to transfect HepG2 cells with equivalent efficiency as untreated
      condensed plasmid DNA. Alternatively, uncondensed plasmid DNA was rapidly
      fragmented by sonication and serum endonucleases and resulted in negligible gene
      expression following condensation with peptide. Cationic lipid/DNA complexes were
      only partially effective at stabilizing DNA in serum compared to the complete
      stabilization afforded by peptide/DNA condensation. These results indicate that
      the stabilization afforded by condensation with a peptide protects DNA during
      formulation and preserves its structure in serum. These functions are important
      to achieve optimal gene expression from a nonviral gene delivery system.

PMID- 9607941
TI  - Cloning, expression, and characterization of the squid Na+-Ca2+ exchanger (NCX
      SQ1).
AB  - We have cloned the squid neuronal Na+-Ca2+ exchanger, NCX-SQ1, expressed it in
      Xenopus oocytes, and characterized its regulatory and ion transport properties in
      giant excised membrane patches. The squid exchanger shows 58% identity with the
      canine Na+-Ca2+ exchanger (NCX1.1). Regions determined to be of functional
      importance in NCX1 are well conserved. Unique among exchanger sequences to date,
      NCX-SQ1 has a potential protein kinase C phosphorylation site (threonine 184)
      between transmembrane segments 3 and 4 and a tyrosine kinase site in the Ca2+
      binding region (tyrosine 462). There is a deletion of 47 amino acids in the large
      intracellular loop of NCX-SQ1 in comparison with NCX1. Similar to NCX1,
      expression of NCX-SQ1 in Xenopus oocytes induced cytoplasmic Na+-dependent 45Ca2+
      uptake; the uptake was inhibited by injection of Ca2+ chelators. In giant excised
      membrane patches, the NCX-SQ1 outward exchange current showed Na+-dependent
      inactivation, secondary activation by cytoplasmic Ca2+, and activation by
      chymotrypsin. The NCX-SQ1 exchange current was strongly stimulated by both ATP
      and the ATP-thioester, ATP gamma S, in the presence of F- (0.2 mM) and vanadate
      (50 microM), and both effects reversed on application of a phosphatidylinositol
      4',5'-bisphosphate antibody. NCX1 current was stimulated by ATP, but not by ATP
      gamma S. Like NCX1 current, NCX-SQ1 current was strongly stimulated by
      phosphatidylinositol-4',5'-bisphosphate liposomes. In contrast to results in
      squid axon, NCX-SQ1 was not stimulated by phosphoarginine (5-10 mM). After
      chymotrypsin treatment, both the outward and inward NCX-SQ1 exchange currents
      were more strongly voltage dependent than NCX1 currents. Ion concentration jump
      experiments were performed to estimate the relative electrogenicity of Na+ and
      Ca2+ transport reactions. Outward current transients associated with Na+
      extrusion were much smaller for NCX-SQ1 than NCX1, and inward current transients
      associated with Ca2+ extrusion were much larger. For NCX-SQ1, charge movements of
      Ca2+ transport could be defined in voltage jump experiments with a low
      cytoplasmic Ca2+ (2 microM) in the presence of high extracellular Ca2+ (4 mM).
      The rates of charge movements showed "U"-shaped dependence on voltage, and the
      slopes of both charge-voltage and rate-voltage relations (1,600 s-1 at 0 mV)
      indicated an apparent valency of -0.6 charges for the underlying reaction.
      Evidently, more negative charge moves into the membrane field in NCX-SQ1 than in
      NCX1 when ions are occluded into binding sites.

PMID- 9607944
TI  - Physicochemical characterization of the orthorhombic polymorph of paracetamol
      crystallized from solution.
AB  - This paper describes a method for the laboratory-scale crystallization of the
      orthorhombic polymorph (form II) of paracetamol (acetaminophen) from solution.
      Its structure has been determined by single-crystal X-ray crystallography at 298
      K (to confirm the results of data published in 1974) and at 123 K (to improve the
      overall accuracy of the structure determination). Despite considerable effort by
      many investigators, the crystallization of form II from solution, using the
      method given in the 1974 structure report, has been elusive. The incentive for
      this effort is that form II, unlike commercial paracetamol (form I), undergoes
      plastic deformation and is suitable for direct compression. Consequently, the
      ability to produce form II in quantity has attracted much interest because of the
      potential commercial benefits to be gained by not using binders during the
      manufacture of tablets. However, until now, the only method that has been
      reported for the bulk preparation of form II has been to grow it as
      polycrystalline material from fused form I. This study also compares the solid
      state properties of form II with those of form I, with particular emphasis on the
      crystallography (both X-ray and optical), crystal morphology, thermal behavior,
      and compaction properties.

PMID- 9607945
TI  - Mixing behavior of colyophilized binary systems.
AB  - The purpose of this study was to investigate the factors which govern the mixing
      of amorphous sucrose with trehalose, poly(vinylpyrrolidone) (PVP), dextran, and
      poly(vinylpyrrolidone-co-vinyl acetate) (PVP/VA). These materials were chosen as
      model systems to represent multicomponent freeze-dried pharmaceutical
      preparations. Mixtures were prepared by colyophilization of the components from
      aqueous solutions. The glass transition temperatures (Tg) of these mixtures were
      measured using differential scanning calorimetry (DSC) and were compared to
      predictions based on simple mixing rules. FT-Raman spectroscopy was used to probe
      selected mixtures for evidence of molecular interactions between components.
      Colyophilized mixtures were confirmed to be amorphous by X-ray powder
      diffraction. The Tg values of the various mixtures generally were lower than
      values predicted from free volume and thermodynamic models, indicating that
      mixing is not ideal. The FT-Raman spectra of colyophilized sucrose-PVP and
      sucrose-PVP/VA mixtures provided evidence for interaction between the components
      through hydrogen bonding. Hydrogen bonds formed between components in
      colyophilized sucrose-additive mixtures are formed at the expense of hydrogen
      bonds within sucrose and in some cases within the additive. A thermodynamic
      analysis of these mixtures indicates that mixing is endothermic, which is
      consistent with a net loss in the degree of hydrogen bonding on mixing. There is
      also a positive excess entropy of mixing which accompanies the net loss in
      hydrogen bonds. Despite this gain in excess entropy, the excess free energy of
      mixing is positive, consistent with the observed deviations in Tg from values
      predicted using models which assume ideal mixing.

PMID- 9607946
TI  - Nicotine transport in a human choriocarcinoma cell line (JAR).
AB  - Smoking is a major health problem in pregnancy resulting in intrauterine growth
      retardation and birth complications. Nicotine, a toxic component of cigarette
      smoke, interferes with amino acid transport in the placenta and stimulates
      catecholamine release resulting in uteroplacental vasoconstriction.
      Transplacental transport of nicotine may be an important determinant of placental
      and fetal exposure. Our aim was to determine the mechanism of nicotine transport
      in the human choriocarcinoma cell line, JAR, as a model for the placenta. JAR
      cells were subcultured in 12-well plates following trypsinization at a seeding
      density of 0.5 x 10(6) cells/well (1.3 x 10(5) cells/cm2). Uptake studies of
      [3H]nicotine were carried out in JAR cell monolayers on day 2 after plating.
      [3H]Nicotine uptake was saturable (Km 156 microM), sensitive to temperature, and
      inhibited by unlabeled nicotine and various organic cations including
      mecamylamine and quinidine, but not by guanidine, tetraethylammonium (TEA), or
      neurotransmitters. Counterflux of [3H]nicotine uptake was produced by unlabeled
      nicotine and mecamylamine but not by cotinine or acetylcholine, consistent with a
      carrier-mediated transport process. The uptake could be driven by an inside
      negative membrane potential or by an outwardly directed pH gradient. This is the
      first demonstration of a carrier-mediated transport mechanism for nicotine in a
      human cell line. This transport mechanism may have implications to the
      disposition of nicotine in the human placenta.

PMID- 9607947
TI  - Interaction of recombinant interleukin-2 with liposomal bilayers.
AB  - Liposomes have been employed as a delivery system for recombinant interleukin-2
      (rIL-2) in cancer immunotherapy. In this study the effects of the rIL-2-bilayer
      interaction on protein structure were investigated. It was shown that rIL-2
      adsorbs to liposomal membranes when added to preformed liposomes. Polarized
      fluorescence decay studies showed that the single tryptophan in "native" rIL-2
      has a relatively large motional freedom, although iodide quenching of this
      residue's fluorescence was relatively ineffective. However, adsorption of rIL-2
      to liposomes alters this situation dramatically- fluorescence intensity increased
      2-fold and the residue became more susceptible to iodide quenching. At the same
      time, the average fluorescence lifetime of the fluorophore is extended.
      Interestingly, circular dichroism studies showed that no major conformational
      changes occurred in rIL-2's secondary structure upon adsorption. These
      observations support the hypothesis that intramolecular quenching takes place in
      the native rIL-2 molecule, which is abrogated upon adsorption to the liposomal
      membrane, resulting in a higher fluorescence intensity. Fluorescence anisotropy
      decay experiments indicate that the protein forms self-aggregates under the low
      ionic strength conditions used, confirming the earlier observations on the
      tendency of the protein to precipitate in salt-containing media.

PMID- 9607948
TI  - Colon-specific drug delivery based on a cyclodextrin prodrug: release behavior of
      biphenylylacetic acid from its cyclodextrin conjugates in rat intestinal tracts
      after oral administration.
AB  - An antiinflammatory drug biphenylylacetic acid (BPAA) as a model drug was
      selectively conjugated onto one of the primary hydroxyl groups of alpha-, beta-,
      and gamma-cyclodextrins (CyDs) through an ester or amide linkage, and the in vivo
      drug release behavior of these prodrugs in rat gastrointestinal tracts after oral
      administration was investigated. The CyD prodrugs were stable in rat stomach and
      small intestine and negligibly absorbed from these tracts. Three to six hours
      after the oral administration, most of the prodrugs had moved to the cecum and
      colon. The alpha- and gamma-CyD amide prodrugs were hydrolyzed to the maltose
      conjugate in the cecum and colon, and these prodrugs and the conjugate were
      negligibly absorbed. On the other hand, the alpha- and gamma-CyD ester prodrugs
      produced BPAA in the cecum and colon, and BPAA appeared in the blood after 3-6 h.
      Both beta-CyD amide and ester prodrugs released only small or negligible amounts
      of the maltose conjugate or BPAA in the cecum and colon, within 24 h, probably
      due to the low solubility in the biological media. Further, the antiinflammatory
      effect of the gamma-CyD ester prodrug was evaluated using the model of carageenan
      induced acute edema in rat paw and compared with those of BPAA alone and the
      BPAA/beta-CyD complex prepared by the kneading method in a molar ratio of 1:1. In
      the case of the beta-CyD complex, a rapid antiinflammatory response was observed,
      compared to BPAA alone, because the drug is mainly absorbed from the small
      intestine after a fast dissolution of the complex. In sharp contrast, the gamma
      CyD ester prodrug needed a fairly long lag time to exhibit the drug activity,
      because BPAA is produced after the prodrug had reached the cecum and colon. The
      present results clearly suggest that the CyD prodrug approach can provide a
      versatile means for constructions of not only colon-specific delivery systems but
      also delayed-release system of certain drugs.

PMID- 9607949
TI  - Transcutaneous delivery of prostaglandin E1: in vitro and laser doppler flowmetry
      study.
AB  - The aim of this study was to assess the rate and extent of transcutaneous
      delivery of prostaglandin E1 (PGE1) from various formulations [liposomal, novel
      biphasic, and nonliposomal (oil/water cream) delivery systems] in vitro using
      diffusion cells and in vivo using laser doppler flowmetry, to aid in the
      development of a topically active preparation for the treatment of male sexual
      dysfunction. Percutaneous absorption through adult human foreskin was tested in
      flow-through diffusion cells using [3H]PGE1. Nine healthy volunteers participated
      in the crossover, randomized, double-blind, placebo-controlled study, where 0.1 g
      of each preparation was applied to a 4 cm2 area on the forearm. Laserflo BPM2
      blood perfusion monitor with Model P-430 skin probe was used for evaluating skin
      blood perfusion. Encapsulation of PGE1 into novel biphasic delivery systems
      resulted in significantly increased skin blood perfusion relative to traditional
      liposomal, nonliposomal, and placebo formulations (6.25 +/- 1.58 vs 2.72 +/-
      0.79, 0.53 +/- 0.64, and 0.58 +/- 0.06 mLLD/min/100 g, respectively, n = 9). The
      in vitro absorption of PGE1 through foreskin correlated well with the in vivo
      data (respective permeability coefficients 3.33, 1.57, and 1. 40 x 10(-4) cm/h).
      Formulation parameters greatly influence the absorption of PGE1 through skin as
      measured by laser doppler flowmetry, but by the application of a novel topical
      delivery technology, a significant enhancement of PGE1 delivery can be achieved.

PMID- 9607950
TI  - Partial permselective coating adds an osmotic contribution to drug release from
      swellable matrixes.
AB  - A swellable matrix tablet is described which is partially coated with cellulose
      acetate (CA) to obtain a film having the shape of a cup, whose permeability to
      water and solutes was altered by mixing increasing amounts of poly(ethylene
      glycol) 400 (PEG). The drug-release mechanism from such systems was assessed by
      carrying out drug-release experiments both in water and saline solutions. Drug
      permeability through the polymeric cup and SEM analysis on the films were also
      performed. It was found that the systems exhibited drug-release kinetics very
      close to linearity. The mechanisms governing drug release were (i) drug diffusion
      through the uncoated gel layer, (ii) drug transport through the gel layer due to
      the osmotic pressure difference, and (iii) drug diffusion through the cup pores.
      The relative importance of each contribution depended on the amount of PEG in the
      film. The systems with a cup containing 1%, 13%, and 33% PEG w/w behaved in part
      as osmotic systems, whereas the system having a permeable cup behaved as a hybrid
      reservoir system. These modifications of the coating permeability introduce a
      further possibility of modulating drug-release kinetics and lead to a reduced
      dependence of swellable matrix tablet release on environmental conditions.

PMID- 9607951
TI  - Transit compartments versus gamma distribution function to model signal
      transduction processes in pharmacodynamics.
AB  - Delayed effects for pharmacodynamic responses can be observed for many signal
      transduction processes. Three approaches are summarized in this report to
      describe such effects caused by cascading steps: stochastic process model, gamma
      distribution function, and transit compartment model. The gamma distribution
      function, a probability density function of the waiting time for the final step
      in a stochastic process model, is a function of time with two variables: number
      of compartments N, and the expected number of compartments occurring per unit
      time k. The parameter k is equal to 1/tau, where tau is the mean transit time in
      the stochastic process model. Effects of N and k on the gamma distribution
      function were examined. The transit compartment model can link the
      pharmacokinetic profile of the tested compound, receptor occupancy, and cascade
      steps for the signal transduction process. Time delays are described by numbers
      of steps, the mean transit time tau, and the amplification or suppression of the
      process as characterized by a power coefficient gamma. The effects of N, tau, and
      gamma on signal transduction profiles are shown. The gamma distribution function
      can be utilized to estimate N and k values when the final response profile is
      available, but it is less flexible than transit compartments when dose-response
      relationships, receptor dynamics, and efficiency of the transduction process are
      of concern. The transit compartment model is useful in
      pharmacokinetic/pharmacodynamic modeling to describe precursor/product
      relationships in signal transduction process.

PMID- 9607952
TI  - Kinetics and mechanism of release from glyceryl monostearate-based implants:
      evaluation of release in a gel simulating in vivo implantation.
AB  - The overall objective of the study was to design an implantable delivery system
      based on glyceryl monostearate (GMS) for the site-specific delivery of
      antibiotics for the prevention of surgical wound infection. To design the
      implant, a release method had to be developed that simulate the in vivo
      implantation conditions to be able to predict the release characteristics from
      the implants when they are actually used in vivo. Also, identifying the release
      kinetics and mechanism and evaluating the factors that influence the release of
      drugs from the GMS-based matrix were necessary to allow further design of
      implants that could yield a desired release rate. The release of cefazolin was
      monitored from GMS matrixes implanted into agar gel, simulating subcutaneous
      tissues with respect to viscosity and water content. The gel method resulted in
      observation of spatial and temporal concentration profiles in the immediate
      vicinity of the implants, indicating the benefits of local drug delivery;
      however, there was no significant difference between the cumulative release
      profiles by the gel method or the vial release method. The release of cefazolin
      from the GMS-based matrix with the vial method followed Higuchi's square root of
      time kinetics. The release rate was found to be directly proportional to
      cefazolin load (A) and the surface area (SA) of the matrix as expressed by the
      following equation: = 0.24ASA. On the basis of this equation, one can design a
      variety of GMS matrixes that would result in a desired release rate or release
      duration. This also indicated that cefazolin release followed the release
      kinetics of a freely soluble drug from an insoluble matrix and hence it is a
      diffusion-controlled process. The effect of drug solubility on the release
      kinetics was determined by comparing the release kinetics of the poorly water
      soluble ciprofloxacin (0.16 mg/mL) to that of the highly water soluble cefazolin
      (325 mg/mL). The release duration of ciprofloxacin (80 h) was longer than that of
      cefazolin (25 h) from identical GMS matrixes. Although ciprofloxacin release was
      initially controlled by the matrix, agitation accelerated disintegration of the
      matrix and release due to its poor solubility, and ciprofloxacin release appeared
      to be a dissolution-controlled process following zero-order release kinetics.

PMID- 9607953
TI  - A combined calorimetric and semiempirical quantum chemical approach to describe
      the solution thermodynamics of drugs.
AB  - A combined calorimetric-semiempirical quantum chemical approach is presented to
      calculate the energy changes for the solution process of drugs. The aim of the
      presented approach is to understand the elementary steps of the solution process
      and to propose strategies for an improvement of solubility of drugs. On the basis
      of the Hess theorem, an alternative route for the solution process via
      sublimation of the solute, creation of a cavity for the solute in the solvent,
      transfer into this cavity, and the reorganization of the dipoles of the solute
      and the solvent can be taken. This approach allows the calculation of all
      energies describing the direct solution process as well as the alternative route.
      The approach was tested on 11 substances of different molecular structure by
      calculating the standard free energy of the specific phase transition. A general
      way to calculate the energy changes of all phase transitions is given. The
      complete cycle with DeltaG, DeltaH, and DeltaS was calculated exemplary for the
      nonsteroidal analgesic ibuprofen. The low solubility of ibuprofen was shown to be
      due to its high standard free energy of sublimation. Therefore the preparation of
      solid dispersions could be considered.

PMID- 9607954
TI  - Penetration of dimyristoylphosphatidylcholine monolayers and bilayers by model
      beta-blocker agents of varying lipophilicity.
AB  - Penetration of model beta-blockers, propranolol, oxprenolol, metaprolol, and
      nadolol, into dimyristoylphosphatidylcholine (DMPC) monolayers cast on a pH 7.4
      phosphate buffer (mu = 0.155 adjusted with NaCl) at 25 degreesC was monitored
      using a film balance equipped with a Wilhelmy plate for measuring changes in
      surface pressure. Drug solution (pH 7.4) is injected below the surface of the
      monolayer. The difference in surface pressure, Delta pi, for each drug
      concentration added to the monolayer was measured at equilibrium. Delta pi
      increased with increasing drug concentration. Consistent with the relative
      lipophilicities, the Delta pi vs drug concentration slopes were as follows:
      propranolol > metaprolol > oxprenolol > nadolol. The intrinsic surface activity
      of the beta-blockers was also determined in the absence of the lipid.
      Differential scanning calorimetry (DSC) measurements were also made on DMPC
      bilayers in the above buffer. DMPC suspended in buffered drug solutions were
      scanned over a temperature range of 5 degrees to 40 degreesC at a scan rate of
      0.091 degreesC/min. The DSC studies indicate that the DMPC thermotropic phase
      behavior is modulated by these compounds as follows: propranolol >> metaprolol
      congruent with oxprenolol > nadolol which agrees with reported partition
      coefficients as well as the above Delta pi observations. However, an accounting
      of the intrinsic surface activity of these compounds results in a lower than
      expected affinity for the DMPC monolayer.

PMID- 9607955
TI  - P-Glycoprotein (P-gp) mediated efflux in Caco-2 cell monolayers: the influence of
      culturing conditions and drug exposure on P-gp expression levels.
AB  - The influence of cell culture conditions and previous drug exposure on P
      glycoprotein (P-gp) expression levels in Caco-2 cells was determined. In this
      study, the expression of P-gp is demonstrated (i) visually by confocal laser
      scanning microscopy (CLSM), (ii) functionally by transport studies with
      substrates of the efflux pump, and (iii) quantitatively by flow cytometry (FCM)
      analysis using specific monoclonal antibodies (anti P-gp MRK 16 as an external
      antibody and P-GlycoCheck C219 as an internal antibody). Trypsinization of the
      cells after reaching confluence led to a decrease of P-gp expression levels,
      while trypsinization before reaching confluence led to an increase after long
      term cultivation. Culturing the cells on polycarbonate filters did not elicit a
      significant change of P-gp expression over time in culture, whereas in plastic
      flasks (polystyrene) a decrease was detected. Using CLSM a strong fluorescence on
      the apical side of Caco-2 cell monolayers was observed, as a result of incubation
      with MRK 16 as primary and IgG Cy5 as secondary antibody. Previous drug exposure
      of the cells showed that verapamil, celiprolol, and vinblastine induced the P-gp
      expression, while metkephamid (MKA) decreased the P-gp expression level as
      compared to the control. Permeation studies consolidated the theory that P-gp is
      expressed in the Caco-2 cells examined. For talinolol and MKA, a higher transport
      from basolateral to apical side than from apical to basolateral could be
      measured. Incubation of the cell monolayer with MRK 16 reduced the secretion
      process to the apical side, but did not influence [3H]mannitol flux. Caco-2 cells
      seem to be a suitable cell line model for P-gp-mediated secretion studies.
      However, the variability of the P-gp expression requires careful control when
      this model is to be used in quantitative structure/secretion studies.

PMID- 9607956
TI  - Evaluation of plasmid DNA for in vivo gene therapy: factors affecting the number
      of transfected fibers.
AB  - Gene transfer by intramuscular injection of plasmid DNA has potential application
      in gene therapy. We examined factors affecting the number of expressing fibers,
      in contrast to total expression, following injection of plasmid DNA. Barium
      chloride proved effective in inducing muscle necrosis and regeneration in mice,
      and this increased the number of fibers expressing a reporter gene. Coinjection
      of ion-channel modulators did not increase the number of positive fibers, but
      increasing dose and repeated administration of plasmid did. Importantly, the
      plasmid size (7-16 kb) did not affect the number of fibers expressing the
      transgene, in both normal and regenerating muscle.

PMID- 9607957
TI  - A partial area difference analysis for estimating elimination rate constants and
      distribution volumes of metabolites.
AB  - The true elimination rate constant of a metabolite is calculated using a partial
      area difference analysis. A linear pharmacokinetic model which describes
      clearances of parent and metabolite is developed. The model makes no restrictions
      on the route of administration of the parent but requires time-invariant kinetics
      for both parent and metabolite. Carbamazepine (CBZ), an antiepileptic, is
      metabolized to the 10,11-epoxide (CBZE), which is further hydrated to the trans
      dihydrodiol (CBZD). Plasma data of the metabolites after a 200-mg single oral
      dose of Tegretol chewable tablets is used to demonstrate the applicability of the
      method. Elimination rate constants calculated using partial area analysis are
      0.087 +/- 0.015 (h-1) and 0.056 +/- 0.014 (h-1) for CBZE and CBZD, respectively.
      These correspond to an average half-life of 8.0 h for CBZE and 12.4 h for CBZD,
      which suggest elimination-rate-limited disappearance of CBZD. The elimination
      rate constants for CBZE and CBZD calculated using partial areas are comparable to
      those in the literature determined after oral administration of CBZE. Volumes of
      distribution of CBZE and CBZD are also estimated to be 0.57 +/- 0.11 L/kg and
      0.76 +/- 0.24 L/kg, respectively. The higher values observed with CBZD volumes of
      distribution are attributed to the higher plasma free fraction of the diol
      relative to CBZE.

PMID- 9607958
TI  - Determination of the glass properties of D-mannitol using sorbitol as an
      impurity.
AB  - Due to its strong tendency to crystallize, the glass properties of mannitol
      cannot be measured directly. However, because mannitol can exist in a fully or
      partially amorphous state in drug formulations, it is important to determine the
      glass properties of mannitol. We obtained the glass properties of mannitol by
      introducing a small amount of sorbitol, an isomer of mannitol, to delay the onset
      of crystallization. Extrapolation to zero sorbitol concentration yielded the
      following properties for the mannitol glass: Tg onset = 10.7(o)C, Tg midpoint=
      12.6( o)C, Tg end = 18.4 degreesC and DeltaCp = 1.27 J/g/K. In addition, we
      estimated the following parameters of the mannitol glass from the width of glass
      transition using the results of Moynihan (J. Am. Ceram. Soc. 1993, 76, 1081) and
      Angell (J. Phys. Chem. 1994, 98, 13780): DeltaH (at Tg onset) = 103 kcal/mol, D =
      11, and T0 = 222 K. The value of T0 is consistent with the Kauzmann temperature
      TK (236 K) obtained calorimetrically. The properties of the mannitol glass may be
      useful for predicting the behavior of amorphous mixtures containing mannitol.

PMID- 9607959
TI  - Spontaneous opalescence of aqueous gamma-cyclodextrin solutions: complex
      formation or self-aggregation?

PMID- 9607961
TI  - Inhibition of the conjugation of PABA with glycine in vitro by sulfamoyl benzoic
      acids, sulfonamides, and penicillins and its relation to tubular secretion 

PMID- 9607960
TI  - Pharmacokinetic aspects of palinavir, an HIV protease inhibitor, in Sprague
      Dawley rats.

PMID- 9607962
TI  - A mechanistic study of griseofulvin dissolution into surfactant solutions in
      laminar flow conditions 

PMID- 9608003
TI  - Early captopril treatment prevents hypertrophydependent gene expression in hearts
      of SHR.
AB  - Treatment of spontaneously hypertensive rats (SHR) with captopril (100 mg . kg-1
      . day-1) throughout development and during the first 16 wk of life leads to a
      reduction in blood pressure and left ventricular hypertrophy. Blood pressures and
      hypertrophy are reduced in these animals (vs. untreated SHR) for up to 24 wk
      after discontinuation of the drug. We used conventional blot hybridization and
      Western analysis to examine hypertrophy-dependent gene expression during this
      period. Ventricular expression of the atrial natriuretic peptide gene was reduced
      by >90% at 16 wk of age in the captopril-treated SHR. Expression increased in the
      24 wk after discontinuation of treatment, but remained well below that of the
      untreated SHR. A similar reduction in ventricular c-myc gene expression was seen
      with captopril treatment. Neither renal expression of the atrial natriuretic
      peptide gene nor ventricular expression of the c-fos gene was affected by
      captopril. This study demonstrates that captopril treatment during a critical
      period of development in the SHR leads to a sustained reduction in hypertrophy
      dependent myocardial gene expression, which does not revert to levels seen in the
      untreated SHR after discontinuation of the drug.

PMID- 9608004
TI  - Leptin produces anorexia and weight loss without inducing an acute phase response
      or protein wasting.
AB  - The ob gene product leptin is known to produce anorexia and loss of body fat when
      chronically administered to both lean and genetically obese mice. The current
      study was undertaken to examine whether administration of recombinant leptin in
      quantities sufficient to produce decreases in food intake and body weight and
      alterations in body composition would elicit either an hepatic acute phase
      protein response or preferential loss of carcass lean tissue. Mice were
      administered increasing quantities of recombinant human leptin or human tumor
      necrosis factor-alpha as a positive control. Although leptin (at 10 mg/kg body
      wt) produced significant anorexia and weight loss (both P < 0.05), human leptin
      administration did not appear to induce an hepatic acute phase protein response
      in either lean or genetically obese mice, as determined by protein synthetic
      rates in the liver or changes in the plasma concentration of the murine acute
      phase protein reactants, amyloid A, amyloid P, or seromucoid (alpha1-acid
      glycoprotein). In addition, human leptin administration did not induce a loss of
      fat-free dry mass (protein) in lean or obese animals. The findings suggest that
      at doses adequate to alter food intake and body weight leptin is not a
      significant inducer of the hepatic acute phase response nor does leptin promote
      the preferential loss of somatic protein characteristic of a chronic inflammatory
      process.

PMID- 9608005
TI  - Regulation of intracellular pH in proximal tubules of avian long-looped mammalian
      type nephrons.
AB  - In nonperfused proximal tubules isolated from chicken long-looped mammalian-type
      nephrons, intracellular pH (pHi), measured with the pH-sensitive fluorescent dye
      2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein, was approximately 7.3 under
      control conditions (HEPES-buffered medium with pH 7.4 at 37 degrees C) and was
      reduced to approximately 7.0 in response to NH4Cl pulse. The rate of recovery of
      pHi from this level to the resting level was 1) significantly reduced by the
      removal of Na+ from the bath, 2) significantly increased by the removal of Cl-
      from the bath, 3) unchanged by the removal of both Na+ and Cl- from the bath, 4)
      significantly reduced by the addition of either ethylisopropylamiloride or DIDS
      to the bath, 5) significantly increased by a high bath K+ concentration, and 6)
      unchanged by the addition of Ba2+ to the bath. These data suggest that both Na+
      coupled and Cl--coupled basolateral acid-base fluxes are involved in determining
      the rate of recovery of pHi after acidification. The most likely ones to be
      important in regulating pHi are a Na+/H+ exchanger and a Na+-coupled Cl-/HCO-3
      exchanger. In birds, long-looped mammalian-type nephrons resemble short-looped
      transitional nephrons but differ markedly from superficial loopless reptilian
      type nephrons.

PMID- 9608006
TI  - Catecholamines inhibit growth in fetal sheep in the absence of hypoxemia.
AB  - To evaluate contributions of catecholamines to inhibition of growth during
      chronic hypoxemia or severe undernutrition, epinephrine (Epi; 0.25-0.35 microg .
      kg-1 . min-1) or norepinephrine (NE; 0.5-0.7 microg . kg-1 . min-1) was
      administered to normoxemic fetuses in twin-pregnant ewes for 8-12 days, from 125
      to 127 days of gestation. Both had similar effects and decreased fetal weight by
      approximately 20% relative to control twins (P < 0.01). Weight gain ceased during
      infusion of Epi or NE (-21 +/- 14.8 or 14 +/- 20.9 g/day), whereas controls
      gained 93 +/- 13.2 g/day (P < 0.01). Effects on tissues and organs varied, spleen
      and thymus being most retarded, whereas brain weight and skeletal measures were
      affected little. Selected muscles from infused fetuses weighed 72% of those in
      controls. Growth ceased during infusion (P < 0.001). Weight gain of hindlimb
      bones was negligible, but length increased at 56% of control rates. Arterial
      blood CO2 and plasma insulin were decreased (P < 0.001), but plasma glucose,
      growth hormone, and blood oxygenation increased (P < 0.001). Actions of Epi and
      NE could underlie asymmetrical growth retardation occurring in many adverse
      physiological situations during fetal development.

PMID- 9608007
TI  - A role for NMDA receptors in posthypoxic frequency decline in the rat.
AB  - Posthypoxic frequency decline (PHFD) refers to the undershoot in respiratory
      frequency that follows brief hypoxic exposures. Lateral pontine neurons are
      required for PHFD. The neurotransmitters involved in the circuit that activate
      and/or are released by these pontine neurons regulating PHFD are unknown. We
      hypothesized that N-methyl-D-aspartate (NMDA) receptors are required for PHFD,
      because of the similarity in respiratory pattern after blocking lateral pontine
      activity or NMDA receptors. Furthermore, we hypothesized that the location of
      these NMDA receptors could be visualized by optimizing binding affinity with
      spermidine. In vagotomized, anesthetized rats (n = 16), cardiorespiratory
      responses to hypoxia (8% O2, 30-90 s) were recorded before and after dizocilpine
      (10 microg-1 mg/kg iv), and NMDA receptors were mapped with [3H]dizocilpine (n =
      6). Dizocilpine elicited a dose-related effect on PHFD, blocking PHFD at high
      doses. Resting arterial blood pressure and breathing frequency decreased with
      high doses of dizocilpine, but the respiratory response to hypoxia remained
      intact. Our novel anatomical data indicate that NMDA receptors were widespread
      but distributed differentially in the brain stem. We conclude that NMDA receptors
      are located in pontine and medullary respiratory-related regions and that PHFD
      requires NMDA-receptor activation.

PMID- 9608008
TI  - Evidence for a role of kallikrein-P6nin system in patients with shock after blunt
      trauma.
AB  - Bradykinin (BK) is activated via plasma and/or tissue kallikrein-kinin (K-K)
      system pathways during hypotension after blunt trauma. The precise role of the K
      K system in human subjects has not been defined. We developed a new method for
      measuring levels of BK in the blood and examined the role of the K-K system in
      patients with shock after trauma. Eight patients were entered into this study. We
      measured the levels of a high-molecular-weight kininogen (HMWK), a low-molecular
      weight kininogen (LMWK), BK, and (1-5)-BK in the blood of patients in an unstable
      state (Pre) and a stable state (Post). At Pre, the blood BK level was
      significantly elevated, the HMWK and LMWK levels were significantly lower, and
      the (1-5)-BK level was significantly higher than the respective levels at Post.
      Our data suggest a significant role for the K-K system in the pathogenesis of
      shock after blunt trauma. This newly developed method for determination of the
      activation of the plasma K-K system appears to be useful for determining the
      severity of a trauma.

PMID- 9608009
TI  - Tubuloglomerular feedback in Dahl rats.
AB  - We have previously demonstrated a loss of autoregulation in Dahl salt-sensitive
      (Dahl-S) rats rendered hypertensive on a high-salt diet. To determine whether
      this was due to a decreased activity of either the myogenic or the
      tubuloglomerular feedback (TGF) response, we tested the TGF response in both Dahl
      S and salt-resistant Dahl rats on high- and low-salt diets. TGF was investigated
      in the closed-loop mode with a videometric technique, in which the response in
      late proximal flow rate to perturbations in Henle flow rate was measured. All
      Dahl rats showed a similar compensatory response to perturbations around the
      natural operating point, with a TGF response that was more efficient than in
      normotensive Sprague-Dawley rats. No evidence of decreased TGF responsiveness in
      hypertensive Dahl-S rats was found. The results suggest that the loss of
      autoregulation in hypertensive Dahl-S rats is due to a compromised myogenic
      response. We also measured the free-flow proximal intratubular pressure in Dahl
      rats. Perfectly regular oscillations were demonstrated in all Dahl series,
      including the hypertensive Dahl-S rats. This is the first demonstration of
      regular oscillations in an experimental rat model of hypertension.

PMID- 9608010
TI  - Ca2+ uptake and Cd2+ accumulation in larval tilapia (Oreochromis mossambicus)
      acclimated to waterborne Cd2+.
AB  - The present study compares the rates of Ca2+ uptake and Cd2+ accumulation in
      tilapia (Oreochromis mossambicus) between larvae preexposed to Cd2+ and naive
      larvae. Preexposure to Cd2+ induces some form of adaptation that attenuates the
      effects of Cd2+ later on. Exposure to Cd2+ decreased the uptake of Ca2+ but did
      not suppress the accumulation rate of Cd2+. A 12-fold increase in 96-h half
      maximal lethal concentration was found in tilapia larvae preexposed to 0.45
      microM Cd2+ from hatching for 3 days in comparison with naive 3-day-old larvae.
      The effects of Cd2+ on Ca2+ influx kinetics in larvae preexposed to 0.18 microM
      Cd2+ for 3 days were examined. The Michaelis constant for Ca2+ in the 0.18 microM
      Cd2+ preexposed larvae did not change significantly in the presence of Cd2+,
      whereas maximal velocity increased by approximately 23%. An enhanced Ca2+ uptake
      efficiency ( approximately 18%) was found in these Cd2+-acclimated larvae. The
      criterion that determines the survival of tilapia larvae encountering Cd2+
      challenge is the degree of interference with Ca2+ homeostasis instead of the
      absolute amount of Cd2+ accumulated.

PMID- 9608011
TI  - Impact of starvation-refeeding on kinetics and protein expression of trout liver
      NADPH-production systems.
AB  - Herein we report on the kinetic and protein expression of glucose-6-phosphate
      dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase, and malic enzyme (ME) in
      the liver of the trout (Oncorhynchus mykiss) during a long-term starvation
      refeeding cycle. Starvation significantly depressed the activity of these enzymes
      by almost 60%, without changing the Michaelis constant. The time response to this
      nutritional stimulus increased with fish weight. The sharp decline in G6PDH and
      ME activities was due to a specific protein-repression phenomenon, as
      demonstrated by molecular and immunohistochemical analyses. Also, the dimeric
      banding pattern of liver G6PDH shifted from the fully reduced and partially
      oxidized forms, predominant in control, to a fully oxidized form, more sensitive
      to proteolytic inactivation. Refeeding caused opposite effects in both protein
      concentration and enzyme activities of about twice the control values in the
      first stages, later reaching the normal enzyme activity levels. Additionally, the
      partially oxidized form of G6PDH increased. The kinetics of these enzymes were
      examined in relation to the various metabolic roles of NADPH. These results
      clearly indicate that trout liver undergoes protein repression-induction
      processes under these two contrasting nutritional conditions.

PMID- 9608012
TI  - NO generation and action during changes in salt intake: roles of nNOS and macula
      densa.
AB  - Micropuncture studies of single nephrons have shown that macula densa solute
      reabsorption via a furosemide-sensitive pathway activates nitric oxide (NO)
      generation via neuronal NO synthase (nNOS). This pathway is enhanced during salt
      loading. We investigated the hypothesis that changes in NO generation via nNOS in
      the macula densa contribute to changes in whole kidney NO generation and action
      during alterations in salt intake. Groups of rats (n = 6-10) were equilibrated to
      high-salt (HS) or low-salt (LS) diets and were administered a vehicle (Veh), 7
      nitroindazole (7-NI; a relatively selective inhibitor of nNOS), or furosemide (F;
      an inhibitor of macula densa solute reabsorption) with volume replacement.
      Compared with LS, excretion of the NO metabolites, NO2 plus NO3 (NOX) was
      increased during HS (LS: 9.0 +/- 0.5 vs. HS: 15.7 +/- 0.8 micromol/24 h; P <
      0.001), but this difference was prevented by 7-NI (LS: 7.4 +/- 1.3 vs. HS: 9.4 +/
      1.6 micromol/24 h; NS). During nonselective blockade of NOS with NG-nitro-L
      arginine methyl ester (L-NAME), renal vascular resistance (RVR) increased more in
      HS than LS (HS: +160 +/- 17 vs. LS: +83 +/- 10%; P < 0.001). This difference in
      response to nonselective NOS inhibition was prevented by pretreatment with 7-NI
      (HS: +28 +/- 6 vs. LS: +34 +/- 8%; NS) or F with volume replacement (HS: +79 +/-
      11 vs. LS: +62 +/- 4%; NS). In conclusion, compared with salt restriction, HS
      intake increases NO generation and renal action that depend on nNOS and macula
      densa solute reabsorption.

PMID- 9608013
TI  - Complement reduction impairs the febrile response of guinea pigs to endotoxin.
AB  - Although it is generally believed that circulating exogenous pyrogens [e.g.,
      lipopolysaccharides (LPS)] induce fever via the mediation of endogenous pyrogens
      (EP) such as cytokines, the first of these, tumor necrosis factor-alpha, is
      usually not detectable in blood until at least 30 min after intravenous
      administration of LPS, whereas the febrile rise begins within 15 min after its
      administration. Moreover, although abundant evidence indicates that circulating
      LPS is cleared primarily by liver macrophages [Kupffer cells (KC)], these do not
      secrete EP in immediate response. This would imply that other factors, presumably
      evoked earlier than EP, may mediate the onset of the febrile response to
      intravenous LPS. It is well known that blood-borne LPS very rapidly activates the
      intravascular complement (C) system, some components of which in turn stimulate
      the quick release into blood of various substances that have roles in the acute
      inflammatory reaction. KC contain receptors for C components and are in close
      contact with afferent vagal terminals in the liver; the involvement of hepatic
      vagal afferents in LPS-induced fever has recently been shown. In this study, we
      tested the hypothesis that the initiation of fever by intravenous LPS involves,
      sequentially, the C system and KC. To test this postulated mechanism, we measured
      directly the levels of prostaglandin E2 (PGE2) in the interstitial fluid of the
      preoptic anterior hypothalamus (POA), the presumptive site of the fever-producing
      controller, of conscious guinea pigs over their entire febrile course, before and
      after C depletion by cobra venom factor (CVF) and before and after elimination of
      KC by gadolinium chloride (GdCl3). CVF and GdCl3 pretreatment each individually
      attenuated the first of the biphasic core temperature (Tc) rises after
      intravenous LPS, inverted the second into a Tc fall, and greatly reduced the
      usual fever-associated increase in POA PGE2. We conclude, therefore, that C
      activation may indeed be pivotal in the induction of fever by intravenous LPS and
      that substance(s) generated presumably by KC in almost immediate reaction to the
      presence of LPS and/or C may transmit pyrogenic signals via hepatic vagal
      afferents to the POA, where they rapidly induce the production of PGE2 and,
      hence, fever.

PMID- 9608014
TI  - Sensitivity of norepinephrine-evoked vasoconstriction to pertussis toxin in the
      old rat.
AB  - In male Wistar rats, the in vitro vasoconstrictor response of the perfused tail
      artery elicited by norepinephrine or serotonin decreased with age (24 mo old vs.
      3 mo old), whereas the fluorescent signal (fura 2) produced by intracellular
      calcium (Ca2+i) mobilization increased. Both vasoconstriction and the increase in
      intracellular calcium concentration elicited by a high-K+, depolarizing solution
      were unaffected by aging. Pertussis toxin, a G protein inhibitor, had no effect
      on vasoconstriction induced by high K+ but diminished vasoconstrictor responses
      to norepinephrine in 3- and 12-mo-old animals but not in 24-mo-old animals.
      Pertussis toxin had no effect on Ca2+i mobilization. The sensitivity of receptor
      activation to pertussis toxin in tail arteries from 24-mo-old animals was
      restored by pretreatment with the alpha-adrenoceptor antagonist nicergoline.
      Nicergoline had no effect on vasoconstriction induced by high K+. Plasma
      norepinephrine concentration rose with age; nicergoline had no effect on this
      rise. We suggest that aging leads to a decrease in the intracellular G protein
      modulated amplification of vasoconstriction produced by receptor activation and
      that this could be linked to the hyperadrenergic state. Ca2+ sensitivity can be
      restored by chronic treatment with an alpha-adrenoceptor antagonist.

PMID- 9608015
TI  - Coronary vascular reactivity is improved by endothelin A receptor blockade in
      DOCA-salt hypertensive rats.
AB  - Endothelin-1 (ET-1) is thought to play an important role in the development of
      deoxycorticosterone acetate (DOCA)-salt hypertension. Because hypertension is
      associated with an increased incidence of coronary artery disease, this study was
      designed to determine if coronary vascular contraction to ET-1 is altered in DOCA
      salt hypertensive rats and to determine the effect of chronic treatment of DOCA
      salt rats with the selective ETA receptor antagonist A-127722. Male Sprague
      Dawley rats were divided into four groups: DOCA, Placebo, DOCA + A-127722, and
      Placebo + A-127722. A-127722 was administered in drinking water at a
      concentration of 8 mg/100 ml. After 3 wk, mean arterial pressure (MAP) was
      significantly enhanced in DOCA-salt compared with Placebo rats. A-127722
      significantly inhibited the increase in MAP. Contraction to ET-1 (10(-11) to 3 x
      10(-8) M) was measured in isolated coronary and mesenteric small arteries (200
      300 micron, intraluminal diameter) maintained at a constant intraluminal pressure
      of 40 mmHg and was significantly impaired in vessels from DOCA-salt compared with
      Placebo rats. Dose-dependent contractions to KCl were also inhibited in coronary,
      but only minimally impaired in mesenteric, arteries of DOCA-salt rats. Inhibition
      of nitric oxide synthase activity did not restore contraction to ET-1 in coronary
      small arteries. However contractions to ET-1 were enhanced in mesenteric small
      arteries. Chronic treatment with A-127722 significantly restored contraction to
      ET-1 in coronary, but not in mesenteric, arteries of DOCA-salt rats. Because ETA
      receptor blockade impairs the development of hypertension and improves coronary
      vascular reactivity, these data indicate that ET-1 plays an important role in
      coronary vascular dysfunction associated with DOCA-salt hypertension.

PMID- 9608016
TI  - Mechanism of vasopressin natriuresis in the dog: role of vasopressin receptors
      and prostaglandins.
AB  - Renal effects of physiological amounts of vasopressin were studied in conscious
      dogs during servocontrolled overhydration (2% body wt). During infusion of
      vasopressin (50 pg . min-1 . kg body wt-1), plasma vasopressin concentration
      increased to 2.30 +/- 0.20 pg/ml compared with 0.12 +/- 0.03 pg/ml during control
      (water diuresis). With vasopressin infusion, urine flow was significantly lower
      (0.30 +/- 0.10 ml/min) and sodium excretion (UNaV) was significantly higher (58.0
      +/- 15.8 micromol/min) than without vasopressin (4.6 +/- 0.4 ml/min and 14.4 +/-
      4.1 micromol/min, respectively). Deamino-[Cys1,D-Arg8]vasopressin, a V2 receptor
      agonist (4 pg . min-1 . kg-1), mimicked the antidiuretic response (0.20 +/- 0.03
      ml/min) without changing UNaV (9.7 +/- 4.4 micromol/min). Indomethacin given
      during arginine vasopressin (AVP) infusion suppressed prostaglandin E2 excretion,
      intensified the antidiuresis (0.10 +/- 0.02 ml/min), and abolished the
      natriuresis (13.4 +/- 3.7 micromol/min). During AVP infusion, UNaV was highly
      correlated (r = 0.85) with prostaglandin E2 excretion. Blood pressure, glomerular
      filtration rate, plasma atrial natriuretic peptide concentration, and the rate of
      proximal tubule reabsorption (derived from lithium clearance) were similar in all
      series. The data indicate that, in the dog, physiological amounts of vasopressin
      can induce natriuresis, probably through activation of non-V2 receptors and the
      intrarenal synthesis of prostaglandins.

PMID- 9608017
TI  - Gastric volume detection after selective vagotomies in rats.
AB  - Rats receiving intragastric infusions of 2.5, 5.0, 7.5, or 10.0 ml of normal
      saline while their pylori are reversibly occluded suppress meal size to the
      smallest infusion and display a dose-dependent reduction across volumes
      [Phillips, R. J., and T. L. Powley. Am. J. Physiol. 271 (Regulatory Integrative
      Comp. Physiol. 40): R766-R779, 1996]. To evaluate the contributions of the vagus
      to this detection of gastric volume, groups prepared with different selective
      vagotomies and equipped with pyloric cuffs and gastric catheters were tested.
      Liquid diet consumption during a 30-min feeding bout was measured after infusions
      of 5.0 and 10.0 ml of normal saline on cuff-open and cuff-closed trials.
      Consistent with earlier observations, sham animals with cuffs closed exhibited
      volume-dependent suppression of food intake to the infusions, and completely
      vagotomized animals did not inhibit feeding in response to the loads. In cuff
      closed trials, the suppression function slopes of the selective vagotomy groups
      were intermediate to those of the shams and the completely vagotomized animals.
      Furthermore, for the different groups, the extent of suppression after vagotomy
      was proportional to the density of the afferent innervation respective branches
      supplied to the stomach. Specifically, the group with the gastric branches spared
      (nonsignificantly attenuated in comparison to shams) and the group with only the
      hepatic branch spared (significantly attenuated with respect to shams) both still
      exhibited significant dose-dependent suppression slopes (compared with
      completes), whereas the group with only celiac branches spared was not
      significantly different from completely vagotomized animals. In sum, the vagus
      nerve mediates the detection of the gastric volumes tested, and the different
      branches of the vagus make distinctive contributions to this afferent feedback.

PMID- 9608018
TI  - Odor structure-activity relationships of carboxylic acids correspond between
      squirrel monkeys and humans.
AB  - With use of a conditioning paradigm, the ability of four squirrel monkeys to
      distinguish n-valeric acid from n-forms and isoforms of other carboxylic acids
      (acetic acid to octanoic acid) was investigated. All four animals were clearly
      able to discriminate between all odor pairs tested and showed a significant
      negative correlation between discrimination performance and structural similarity
      of odorants in terms of differences in carbon chain length of the carboxylic
      acids. Branching of the carbon chain was also found to affect odorant quality
      because all animals performed better in discriminating n-valeric acid from
      isoforms of other carboxylic acids compared with the corresponding n-forms of
      these substances. With use of a triple forced-choice procedure, 10 human subjects
      were tested on the same tasks in parallel and showed a very similar pattern of
      discrimination performance compared with the squirrel monkeys. Thus the results
      of this study provide evidence of well-developed olfactory discrimination ability
      in squirrel monkeys for carboxylic acids and support the assumption that human
      and nonhuman primates may share common principles of odor quality perception.

PMID- 9608019
TI  - Effect of calcitonin on the activity of ANG II-responsive neurons in the rat
      subfornical organ.
AB  - In addition to the well-documented ability of calcitonin to lower blood calcium
      levels, blood-borne calcitonin may also affect neurons located outside the blood
      brain barrier, e.g., in the subfornical organ (SFO), where numerous receptors for
      this peptide have been described. In an in vitro preparation of the rat SFO,
      calcitonin activated 61% of 36 neurons, only 1 neuron was inhibited, and the
      remainder were unresponsive. All but two of the neurons excited by 10(-7) M
      calcitonin were also stimulated by 10(-7) M ANG II. The threshold concentration
      for the excitatory effects of calcitonin was 10(-9) M and was thus similar to ANG
      II. Like ANG II, subcutaneous injection of calcitonin stimulated water intake,
      although to a lower extent. These results suggest that blood-borne calcitonin
      could stimulate drinking by its excitatory effect on neurons in the SFO.
      Calcitonin, which is released during food intake, might be involved in prandial
      drinking, which is presently considered an acquired behavior.

PMID- 9608020
TI  - Effect of acute food deprivation on lactational infertility in rats is reduced by
      leptin administration.
AB  - The goals of these experiments were to determine whether lactational anestrus
      would be prolonged by a 48-h fast at days 13 and 14 postpartum (pp) and, if so,
      to determine whether this effect could be reversed by treatment with the Ob
      protein leptin. We found that food deprivation on days 13 and 14 pp prolonged
      lactational infertility by 7 days and that the nutritional experience of both the
      dam and her litter contributed to this effect. Leptin administration (2.5 mg . kg
      1 . day-1) during food deprivation was sufficient to reduce the length of
      lactational infertility compared with vehicle-treated food-deprived rats (P <
      0.05). Similar leptin treatment in ad libitum-fed animals reduced food intake (P
      < 0.05) and litter growth (P < 0.05) but had no statistically significant effect
      on maternal weight gain or length of lactational infertility. Food-deprived
      lactating animals had lower circulating leptin levels than ad libitum-fed
      lactating animals on day 15 pp (P < 0.05), as determined by RIA. Levels in
      nonlactating rats were higher than in either lactating group (P < 0.05).

PMID- 9608021
TI  - In birds, NHE2 is major brush-border Na+/H+ exchanger in colon and is increased
      by a low-NaCl diet.
AB  - We previously reported that mammalian small intestinal and colonic brush borders
      (BBs) contained both epithelial Na+/H+ exchangers NHE2 and NHE3. We now show
      that, in the avian (chicken) colon, NHE2 is the major functional isoform under
      basal conditions and when stimulated by a low-NaCl diet. Hubbard chickens were
      maintained for 2 wk on a high- or low-NaCl diet. After the chickens were killed,
      the ileum and colon were removed, and BBs were prepared by Mg2+ precipitation and
      22Na and D-[14C]glucose uptake determined in the BB vesicles. NHE2 and NHE3 were
      separated by differential sensitivity to HOE-694 (NHE2 defined as Na+/H+ exchange
      inhibited by 50 microM HOE-694). Chickens on a low-Na+ diet have increased plasma
      aldosterone (10 vs. 207 pg/ml). On the high-NaCl diet, both NHE2 and NHE3
      contributed to ileal and colonic apical Na+/H+ exchange, contributing equally in
      ileum, but NHE2 being the major component in colon (86%). Low-NaCl diet
      significantly increased ileal and colonic BB Na+/H+ exchange; the increase in BB
      Na+/H+ exchange in both ileum and colon was entirely due to an increase in NHE2
      with no change in NHE3 activity. In contrast, low-NaCl diet decreased ileal and
      colonic Na+-dependent D-glucose uptake. Western analysis showed that low-Na+ diet
      increased the amount of NHE2 in the ileal and colonic BB and decreased the amount
      of ileal Na+-dependent glucose transporter SGLT1. Both NHE2 and NHE3 were present
      in the apical but not basolateral membranes (BLM) of ileal and colonic epithelial
      cells. In summary, 1) NHE2 and NHE3 are both present in the BB and not BLM of
      chicken ileum and colon; 2) NHE2 is the major physiological colonic BB Na+/H+
      exchanger under basal conditions; 3) low-NaCl diet, which increases plasma
      aldosterone, increases ileal and colonic BB Na+/H+ exchange and decreases Na+
      dependent D-glucose uptake; 4) the stimulation of colonic BB Na+/H+ exchange is
      due to increased activity and amount of NHE2; and 5) the inhibition of ileal D
      glucose uptake is associated with a decrease in SGLT1 amount. NHE2 is the major
      chicken colonic BB Na+/H+ exchanger.

PMID- 9608022
TI  - Hemodilution mediates changes in renal hemodynamics after acute volume expansion
      in rats.
AB  - The present study examined the factors responsible for triggering renal
      hemodynamic adjustments during acute volume expansion. The renal hemodynamic
      effects of graded volume expansion with 0.9% saline (Sal; 1, 2, and 4% of body
      wt), 7% BSA solution (0.35, 0.70, and 1.4% body wt), or whole blood from a donor
      rat (WBL; 0.35, 0.70, and 1.4% body wt) were compared in rats anesthetized with
      pentobarbital sodium. Neural influences on the kidney were eliminated by vagus
      nerves, baro/chemoreceptor afferents, and renal nerves section, and renal
      perfusion pressure was controlled at constant level (approximately 120 mmHg)
      throughout the experiments. In Sal- and BSA-expanded rats, renal blood flow (RBF)
      increased (Sal: 15, 40, 71%; BSA 17, 49, 107%) and renal vascular resistance
      (RVR) decreased in parallel with the degree of volume expansion (RVR: Sal 17, 31,
      44%; and BSA: 15, 35, 54%). Renal hemodynamics remained unaltered after expansion
      with WBL. In rats expanded with Sal or BSA, correction of the fall of hematocrit
      restored RBF and RVR to control levels. Interference with tubuloglomerular
      feedback by uretheral obstruction had no effect on the decrease in RVR with Sal
      or BSA. Inhibition of the vascular tone by intrarenal papaverine infusion also
      did not alter the renal hemodynamic response to volume expansion with Sal or BSA.
      These findings suggest that the changes in renal hemodynamics after acute
      expansion are likely mediated by changes in rheologic properties of the blood
      rather than by changes in active vascular tone.

PMID- 9608023
TI  - Hypotonic-stimulated taurine efflux in skate erythrocytes: regulation by tyrosine
      phosphatase activity.
AB  - Treatment of skate erythrocytes with FCCP, dinitrophenol, or sodium azide lowers
      ATP levels and inhibits Na+-independent taurine uptake after hypotonic volume
      expansion. Inside-out vesicles isolated from hypotonic volume-expanded cells
      demonstrate greater Na+-independent taurine uptake, and pretreatment of cells
      with FCCP abolishes this stimulation. Addition of ATP to the vesicles does not
      restore stimulated taurine uptake, suggesting that ATP does not act as a ligand
      modulator on the transporter. Therefore the role of protein phosphorylation was
      investigated. Because known protein kinase inhibitors have previously been found
      to have little effect on taurine fluxes in skate erythrocytes, we focused on the
      effects of protein phosphatase inhibition. When volume-expanded cells were
      returned to isotonic medium, taurine flux returned to basal values more slowly
      after treatment with the tyrosine phosphatase inhibitor pervanadate, suggesting
      that dephosphorylation may regulate inactivation. A similar effect of phosphatase
      inhibitors was observed in the inside-out vesicles from volume-expanded cells:
      the reversal of stimulated taurine uptake takes place more slowly in vesicles
      prepared from cells that had been incubated with pervanadate. Band 3, a major
      protein involved in the taurine transport pathway, shows increased tyrosine
      phosphorylation after hypotonic volume expansion. Pervanadate treatment of the
      cells potentiates and prolongs the increased phosphorylation. Therefore tyrosine
      phosphorylation of band 3 may play an important role in the activation of taurine
      fluxes after volume expansion.

PMID- 9608024
TI  - Role of taste in the microstructure of quinine ingestion by rats.
AB  - The microstructure of the licking behavior of water-deprived rats presented with
      either water or quinine during 45-min single-bottle tests was analyzed. The
      chorda tympani (CT) and glossopharyngeal (GL) nerves, which innervate the taste
      buds of the tongue, were transected in deeply anesthetized rats to discern their
      contribution to the behavioral pattern of quinine drinking. Rats were
      presurgically habituated to the testing protocol and postsurgically tested first
      with water and then novel 0.2 mM quinine-HCl in a subsequent session. The
      substantial decrease in intake observed in sham-operated controls (n = 16) when
      quinine was the stimulus was entirely a function of a decrease in lick volume and
      burst size (a run of licks with interlick intervals <1 s). Contrary to the intake
      suppressing effects of quinine, pause duration decreased and burst number
      increased. Combined transection of the CT and GL (n = 6) strikingly opposed all
      of these quinine-induced behavioral changes, whereas CT transection (n = 7) was
      without effect and GL transection (n = 8) had an intermediate influence. These
      results suggest that taste acts more on neural circuits governing burst
      termination as opposed to burst initiation, which, in turn, appears to be more
      sensitive to signals related to physiological state. These findings are discussed
      in terms of other known nerve transection effects on quinine responsiveness, and
      the implications of the microstructural results are considered with respect to
      probabilistic as opposed to deterministic control of licking behavior.

PMID- 9608043
TI  - The historical factor: the biosynthetic relationships between amino acids and
      their physicochemical properties in the origin of the genetic code.
AB  - Two forces are in general, hypothesized to have influenced the origin of the
      organization of the genetic code: the physicochemical properties of amino acids
      and their biosynthetic relationships. In view of this, we have considered a model
      incorporating these two forces. In particular, we have studied the optimization
      level of the physicochemical properties of amino acids in the set of amino acid
      permutation codes that respects the biosynthetic relationships between amino
      acids. Where the properties of amino acids are represented by polarity and
      molecular volume we obtain indetermination percentages in the organization of the
      genetic code of approximately 40%. This indicates that the contingent factor
      played a significant role in structuring the genetic code. Furthermore, this
      result is in agreement with the genetic code coevolution hypothesis, which
      attributes a merely ancillary role to the properties of amino acids while it
      suggests that it was their biosynthetic relationships that organized the code.
      Furthermore, this result does not favor the stereochemical models proposed to
      explain the origin of the genetic code. On the other hand, where the properties
      of amino acids are represented by polarity alone, we obtain an indetermination
      percentage of at least 21.5%. This might suggest that the polarity distances
      played an important role and would therefore provide evidence in favor of the
      physicochemical hypothesis of genetic code origin. Although, overall, the
      analysis might have given stronger support to the latter hypothesis, this did not
      actually occur. The results are therefore discussed in the context of the
      different theories proposed to explain the origin of the genetic code.

PMID- 9608025
TI  - Superoxide-dependent cerebrovascular effects of homocysteine.
AB  - Recent evidence indicates that elevated plasma levels of homocysteine are a risk
      factor for ischemic cerebrovascular diseases. However, little is known about
      cerebrovascular effects of homocysteine. Homocysteine could impair
      cerebrovascular function by metal-catalyzed production of activated oxygen
      species. We studied whether homocysteine, in the presence of Cu2+, alters
      reactivity of cerebral circulation and, if so, whether this effect depends on O-2
      generation. In halothane-anesthetized rats the parietal cortex was exposed and
      superfused with Ringer solution. Cerebrocortical blood flow (CBF) was monitored
      by a laser-Doppler probe. With Ringer solution superfusion, CBF increased with
      hypercapnia (+134 +/- 7%; PCO2 = 50-60 mmHg) and topical application of 10 microM
      ACh (+35 +/- 3%), the NO donor S-nitroso-N-acetylpenicillamine (SNAP, 500 microM;
      +66 +/- 6%), or 1 mM papaverine (+100 +/- 6%; n = 5). Superfusion with 40 microM
      Cu2+ alone did not perturb resting CBF or responses to hypercapnia, ACh, SNAP, or
      papaverine (P > 0.05, n = 5). However, superfusion of homocysteine-Cu2+ reduced
      resting CBF (-28 +/- 4%) and attenuated (P < 0.05) responses to hypercapnia (-31
      +/- 9%), ACh (-73 +/- 6%), or SNAP (-48 +/- 4%), but not papaverine. The effect
      was observed only at 1 mM homocysteine. Cerebrovascular effects of homocysteine
      Cu2+ were prevented by coadministration of superoxide dismutase (SOD; 1,000 U/ml;
      n = 5). SOD alone did not affect resting CBF or CBF reactivity (n = 5). The
      observation that homocysteine-Cu2+ attenuates the response to hypercapnia, ACh,
      and SNAP, but not the NO-independent vasodilator papaverine, suggests that
      homocysteine-Cu2+ selectively impairs NO-related cerebrovascular responses. The
      fact that SOD prevents such impairment indicates that the effect of homocysteine
      is O-2 dependent. The data support the conclusion that O-2, generated by the
      reaction of homocysteine with Cu2+, inhibits NO-related cerebrovascular responses
      by scavenging NO, perhaps through peroxynitrite formation. O-2-mediated
      scavenging of NO might be one of the mechanisms by which hyperhomocysteinemia
      predisposes to cerebrovascular diseases.

PMID- 9608044
TI  - Preference for internucleotide linkages as a function of the number of
      constituents in a mixture.
AB  - Phosphoimidazolide-activated ribomononucleotides (*pN; see Scheme I) are useful
      substrates for the nonenzymatic synthesis of oligonucleotides. In the presence of
      metal ions dilute neutral aqueous solutions of *pN (0.01 M) typically yield only
      small amounts of dimers and traces of oligomers; most of *pN hydrolyzes to yield
      nucleoside 5'-monophosphate (5'NMP). An earlier investigation of *pN reactions in
      highly concentrated aqueous solutions (up to 1.4 M) showed, as expected, that the
      percentage yield of the condensation products increases and the yield of the
      hydrolysis product correspondingly decreases with *pN concentration (Kanavarioti
      1997). Here we report product distributions in reactions with one, two, or three
      reactive components at the same total nucleotide concentration. *pN used as
      substrates were the nucleoside 5'-phosphate 2-methylimidazolides, 2-MeImpN, with
      N = cytidine (C), uridine (U), or guanosine (G). Reactions were conducted as self
      condensations, i. e., one nucleotide only, with two components in the three
      binary U,C, U,G, and C,G mixtures, and with three components in the ternary U,C,
      G mixture. The products are 5'NMP, 5',5'-pyrophosphate-, 2',5'-, 3', 5'-linked
      dimers, cyclic dimers, and a small percentage of longer oligomers. The surprising
      finding was that, under identical conditions, including the same total monomer
      concentration, the product distribution differs substantially from one reaction
      to another, most likely due to changing intermolecular interactions depending on
      the constituents. Even more unexpected was the observed trend according to which
      reactions of the U,C,G mixture produce the highest yield of internucleotide
      linked dimers, whereas the self-condensations produce the least and the reactions
      with the binary mixtures produce yields that fall in between. What is remarkable
      is that the approximately two-fold increase in the percentage yield of
      internucleotide-linked dimers is not due to a concentration effect or a catalyst,
      but to the increased complexity of the system from a single to two and three
      components. These observations, perhaps, provide an example of how increased
      complexity in relatively simple chemical systems leads to organization of the
      material and consequently to chemical evolution. A possible link between
      prebiotic chemistry and the postulated RNA world is discussed.

PMID- 9608045
TI  - On the pattern of polymorphisms at major histocompatibility complex loci.
AB  - The pattern of polymorphisms at major histocompatibility complex loci was studied
      by computer simulations and by DNA sequence analysis. Two types of selection,
      overdominance plus short-term selection and maternal-fetal incompatibility, were
      simulated for a gene family with intra- and interlocus gene conversion. Both
      types of selection were found to be consistent with the observed patterns of
      polymorphisms. It was also found that the more interlocus conversion occurs, the
      higher the divergence becomes at both nonsynonymous and synonymous sites. The
      ratio of nonsynonymous-to-synonymous divergence among alleles decreases as the
      interlocus conversion rate increases. These results agree with the interpretation
      that the rate of interlocus conversion is lower in human genes than in genes of
      other nonprimate mammals. This is because, in the latter, synonymous divergence
      at the ARS (antigen recognition site) is often higher than that at the non-ARS,
      whereas in the former, this is not so. Also, the ratio of nonsynonymous to
      synonymous substitutions at the ARS tends to be higher in human genes than in
      other mammalian genes. The main difference between overdominance plus short-term
      selection and maternal-fetal interaction is that the number of alleles and
      heterozygosity per locus are higher in the latter than in the former under the
      presumed selection intensities. However, the average divergence among alleles
      tends to be lower in the latter than in the former under similar conditions.

PMID- 9608046
TI  - Evolution of a mammalian promoter through changes in patterns of transcription
      factor binding.
AB  - Previously, we identified evolutionarily derived changes in the pattern of
      nuclear factor binding to overlapping sites (termed A, B, and C, in proximal to
      distal order) within the promoter region of the murine D7Rp2e gene. In Mus
      domesticus, strong binding occurs at site B, with weak binding at sites A and C;
      in M. pahari, strong binding is observed at sites A and C, with weak binding at
      site B. The M. pahari-specific occupancy pattern is associated with repression of
      transcription. Presently, we have identified two interspecies changes, a single A
      --> G substitution within site B and a 7-bp indel within site C, that are primary
      determinants of the interspecies differences. These mutations alter both the
      pattern of binding site occupancy and the ability to repress transcription. The
      results are discussed in terms of a model involving a dynamic equilibrium between
      states of binding site occupancy, the nature of which can be modified during
      evolution.

PMID- 9608047
TI  - Characterization of a novel class of interspersed LTR elements in primate
      genomes: structure, genomic distribution, and evolution.
AB  - Retrovirus-like sequences and their solitary (solo) long terminal repeats (LTRs)
      are common repetitive elements in eukaryotic genomes. We reported previously that
      the tandemly arrayed genes encoding U2 snRNA (the RNU2 locus) in humans and apes
      contain a solo LTR (U2-LTR) which was presumably generated by homologous
      recombination between the two LTRs of an ancestral provirus that is retained in
      the orthologous baboon RNU2 locus. We have now sequenced the orthologous U2-LTRs
      in human, chimpanzee, gorilla, orangutan, and baboon and examined numerous
      homologs of the U2-LTR that are dispersed throughout the human genome. Although
      these U2-LTR homologs have been collectively referred to as LTR13 in the
      literature, they do not display sequence similarity to any known retroviral LTRs;
      however, the structure of LTR13 closely resembles that of other retroviral LTRs
      with a putative promoter, polyadenylation signal, and a tandemly repeated 53-bp
      enhancer-like element. Genomic blotting indicates that LTR13 is primate-specific;
      based on sequence analysis, we estimate there are about 2,500 LTR13 elements in
      the human genome. Comparison of the primate U2-LTR sequences suggests that the
      homologous recombination event that gave rise to the solo U2-LTR occurred soon
      after insertion of the ancestral provirus into the ancestral U2 tandem array.
      Phylogenetic analysis of the LTR13 family confirms that it is diverse, but the
      orthologous U2-LTRs form a coherent group in which chimpanzee is closest to the
      humans; orangutan is a clear outgroup of human, chimpanzee, and gorilla; and
      baboon is a distant relative of human, chimpanzee, gorilla, and orangutan. We
      compare the LTR13 family with other known LTRs and consider whether these LTRs
      might play a role in concerted evolution of the primate RNU2 locus.

PMID- 9608048
TI  - Accumulation of transposable elements in the heterochromatin and on the Y
      chromosome of Drosophila simulans and Drosophila melanogaster.
AB  - The elements of the transposon families G, copia, mdg 1, 412, and gypsy that are
      located in the heterochromatin and on the Y chromosome have been identified by
      the Southern blotting technique in Drosophila simulans and D. melanogaster
      populations. Within species, the abundance of such elements differs between
      transposon families. Between species, the abundance in the heterochromatin and on
      the Y chromosome of the elements of the same family can differ greatly suggesting
      that differences within a species are unrelated to structural features of
      elements. By shedding some new light on the mechanism of accumulation of
      transposable elements in the heterochromatin, these data appear relevant to the
      understanding of the long-term interaction between transposable elements and the
      host genome.

PMID- 9608049
TI  - The complete mitochondrial genome of Rhea americana and early avian divergences.
AB  - The complete mitochondrial DNA, mtDNA, molecule of the greater rhea, Rhea
      americana, was sequenced. The size of the molecule is 16,710 nucleotides. The
      organization of the molecule conforms with that described for the chicken and the
      ostrich. It has been shown previously that relative to other vertebrates the
      NADH3 gene of the ostrich has an insertion of one nucleotide in position 174 of
      the gene. The same observation was made in the rhea and in the newly sequenced
      NADH3 gene of the emu, Dromaius novaehollandiae. Comparison with the NADH3 gene
      of the chicken and the rook suggests that the inserted nucleotide may be deleted
      by RNA editing. The divergence between the two struthioniform species, the
      ostrich and the rhea, was molecularly dated at approximately 51 million years
      before present, MYBP. This dating is more recent than commonly acknowledged.
      Phylogenetic analysis of the complete cytochrome b genes of seven avian orders
      placed the Passeriformes basal in the avian tree with the Struthioniformes among
      the remaining Neognathae. These findings challenge the commonly accepted notion
      that the most basal avian divergence is that between the Palaeognathae and
      Neognathae.

PMID- 9608050
TI  - Intraindividual and interspecies variation in the 5S rDNA of coregonid fish.
AB  - This study was designed to characterize further the nontranscribed intergenic
      spacers (NTSs) of the 5S rRNA genes of fish and evaluate this marker as a tool
      for comparative studies. Two members of the closely related North American Great
      Lakes cisco species complex (Coregonus artedi and C. zenithicus) were chosen for
      comparison. Fluorescence in situ hybridization found the ciscoes to have a single
      multicopy 5S locus located in a C band-positive region of the largest
      submetacentric chromosome. The entire NTS was amplified from the two species by
      polymerase chain reaction with oligonucleotide primers anchored in the conserved
      5S coding region. Complete sequences were determined for 25 clones from four
      individuals representing two discrete NTS length variants. Sequence analysis
      found the length variants to result from presence of a 130-bp direct repeat. No
      two sequences from a single fish were identical. Examination of sequence from the
      coding region revealed two types of 5S genes in addition to pseudogenes. This
      suggests the presence of both somatic and germline (oocyte) forms of the 5S gene
      in the genome of Coregonus. The amount of variation present among NTS sequences
      indicates that accumulation of variation (mutation) is greater in this multicopy
      gene than is gene conversion (homogenization). The high level of sequence
      variation makes the 5S NTS an inappropriate DNA sequence for comparisons of
      closely related taxa.

PMID- 9608051
TI  - The Peperomia mitochondrial coxI group I intron: timing of horizontal transfer
      and subsequent evolution of the intron.
AB  - The Peperomia polybotrya coxI gene intron is the only currently reported group I
      intron in a vascular plant mitochondrial genome and it likely originated by
      horizontal transfer from a fungal donor. We provide a clearer picture of the
      horizontal transfer and a portrayal of the evolution of the group I intron since
      it was gained by the Peperomia mitochondrial genome. The intron was transferred
      recently in terms of plant evolution, being restricted to the single genus
      Peperomia among the order Piperales. Additional support is presented for the
      suggestion that a recombination/repair mechanism was used by the intron for
      integration into the Peperomia mitochondrial genome, as a perfect 1:1
      correspondence exists between the intron's presence in a species and the presence
      of divergent nucleotide markers flanking the intron insertion site. Sequencing of
      coxI introns from additional Peperomia species revealed that several mutations
      have occurred in the intron since the horizontal transfer, but sequence
      alterations have not caused frameshifts or created stop codons in the intronic
      open reading frame. In addition, two coxI pseudogenes in Peperomia cubensis were
      discovered that lack a large region of coxI exon 2 and contain a truncated
      version of the group I intron that likely cannot be spliced out.

PMID- 9608052
TI  - Molecular genetics of spectral tuning in New World monkey color vision.
AB  - Although most New World monkeys have only one X-linked photopigment locus, many
      species have three polymorphic alleles at the locus. The three alleles in the
      squirrel monkey and capuchin have spectral peaks near 562, 550, and 535 nm,
      respectively, and the three alleles in the marmoset and tamarin have spectral
      peaks near 562, 556, and 543 nm, respectively. To determine the amino acids
      responsible for the spectral sensitivity differences among these pigment
      variants, we sequenced all exons of the three alleles in each of these four
      species. From the deduced amino acid sequences and the spectral peak information
      and from previous studies of the spectral tuning of X-linked pigments in humans
      and New World monkeys, we estimated that the Ala --> Ser, Ile --> Phe, Gly -->
      Ser, Phe --> Tyr, and Ala --> Tyr substitutions at residue positions 180, 229,
      233, 277, and 285, respectively, cause spectral shifts of about 5, -2, -1, 8, and
      15 nm. On the other hand, the substitutions His --> Tyr, Met --> Val or Leu, and
      Ala --> Tyr at positions 116, 275, and 276, respectively, have no discernible
      spectral tuning effect, though residues 275 and 276 are inside the transmembrane
      domains. Many substitutions between Val and Ile or between Val and Ala have
      occurred in the transmembrane domains among the New World monkey pigment variants
      but apparently have no effect on spectral tuning. Our study suggests that, in
      addition to amino acid changes involving a hydroxyl group, large changes in
      residue size can also cause a spectral shift in a visual pigment.

PMID- 9608053
TI  - The prokaryote-to-eukaryote transition reflected in the evolution of the V/F/A
      ATPase catalytic and proteolipid subunits.
AB  - Changes in the primary and quarternary structure of vacuolar and archaeal type
      ATPases that accompany the prokaryote-to-eukaryote transition are analyzed. The
      gene encoding the vacuolar-type proteolipid of the V-ATPase from Giardia lamblia
      is reported. Giardia has a typical vacuolar ATPase as observed from the common
      motifs shared between its proteolipid subunit and other eukaryotic vacuolar
      ATPases, suggesting that the former enzyme works as a hydrolase in this primitive
      eukaryote. The phylogenetic analyses of the V-ATPase catalytic subunit and the
      front and back halves of the proteolipid subunit placed Giardia as the deepest
      branch within the eukaryotes. Our phylogenetic analysis indicated that at least
      two independent duplication and fusion events gave rise to the larger proteolipid
      type found in eukaryotes and in Methanococcus. The spatial distribution of the
      conserved residues among the vacuolar-type proteolipids suggest a zipper-type
      interaction among the transmembrane helices and surrounding subunits of the V
      ATPase complex. Important residues involved in the function of the F-ATP synthase
      proteolipid have been replaced during evolution in the V-proteolipid, but in some
      cases retained in the archaeal A-ATPase. Their possible implication in the
      evolution of V/F/A-ATPases is discussed.

PMID- 9608054
TI  - Signature sequences in diverse proteins provide evidence of a close evolutionary
      relationship between the Deinococcus-thermus group and cyanobacteria.
AB  - A number of proteins have been identified that contain prominent sequence
      signatures that are uniquely shared by the members of the Deinococcus-Thermus
      genera and the cyanobacterial species but which are not found in any of the other
      eubacterial or archaebacterial homologs. The proteins containing such sequence
      signatures include (1) the DnaJ/Hsp40 family of proteins, (2) DNA polymerase I,
      (3) the protein synthesis elongation factor EF-Tu, and (4) the elongation factor
      EF-Ts. A strong affinity of the Deinococcus-Thermus species to cyanobacteria is
      also seen in the phylogenetic trees based on Hsp70 and DnaJ sequences. These
      results provide strong evidence of a close and specific evolutionary relationship
      between species belonging to these two eubacterial divisions.

PMID- 9608055
TI  - Phylogenetic position of the Hexactinellida within the phylum Porifera based on
      the amino acid sequence of the protein kinase C from Rhabdocalyptus dawsoni.
AB  - Recent analyses of genes encoding proteins typical for multicellularity,
      especially adhesion molecules and receptors, favor the conclusion that all
      metazoan phyla, including the phylum Porifera (sponges), are of monophyletic
      origin. However, none of these data includes cDNA encoding a protein from the
      sponge class Hexactinellida. We have now isolated and characterized the cDNA
      encoding a protein kinase C, belonging to the C subfamily (cPKC), from the
      hexactinellid sponge Rhabdocalyptus dawsoni. The two conserved regions, the
      regulatory part with the pseudosubstrate site, the two zinc fingers, and the C2
      domain, as well as the catalytic domain were used for phylogenetic analyses.
      Sequence alignment and construction of a phylogenetic tree from the catalytic
      domains revealed that the yeast Saccharomyces cerevisiae and the protozoan
      Trypanosoma brucei are at the base of the tree, while the hexactinellid R.
      dawsoni branches off first among the metazoan sequences; the other two classes of
      the Porifera, the Calcarea (the sequence from Sycon raphanus was used) and the
      Demospongiae (sequences from Geodia cydonium and Suberites domuncula were used),
      branch off later. The statistically robust tree also shows that the two cPKC
      sequences from the higher invertebrates Drosophila melanogaster and Lytechinus
      pictus are most closely related to the calcareous sponge. This finding was also
      confirmed by comparing the regulatory part of the kinase gene. We suggest, that
      (i) within the phylum Porifera, the class Hexactinellida diverged first from a
      common ancestor to the Calcarea and the Demospongiae, which both appeared later,
      and (ii) the higher invertebrates are more closely related to the calcareous
      sponges.

PMID- 9608056
TI  - Variable substitution rates of the 18 domain sequences in Artemia hemoglobin.
AB  - The Artemia hemoglobin is a dimer comprising two nine-domain covalent polymers in
      quaternary association. Each polymer is encoded by a gene representing nine
      successive globin domains which have different sequences and are presumed to have
      been copied originally from a single-domain gene. Two different polymers exist as
      the result of a complete duplication of the nine-domain gene, allowing the
      formation of either homodimers or the heterodimer. The total population size of
      18 domains comprising nine corresponding pairs, coupled with the probability that
      they reflect several hundred million years of evolution in the same lineage,
      provides a unique model in which the process of gene multiplication can be
      analyzed. The outcome has important implications for the reliability of local
      molecular clocks. The two polymers differ from each other at 11.7% of amino acid
      sites; however when corresponding individual domains are compared between
      polymers, amino acid substitution fluctuates by a factor of 2.7-fold from lowest
      to highest. This variation is not obvious at the DNA level: Domain pair identity
      values fluctuate by 1. 3-fold. Identity values are, however, uncorrected for
      multiple substitutions, and both silent and nonsilent changes are pooled.
      Therefore, to determine the variability in relative substitution rates at the DNA
      level, we have used the method of Li (1993, J Mol Evol 36:96-99) to determine
      estimates of nonsynonymous (KA) and synonymous (KS) substitutions per site for
      the nine pairs of domains. As expected, the overall level of silent substitutions
      (KS of 56. 9%) far exceeded nonsilent substitutions (KA of 6.7%); however, for
      corresponding domain pairs, KA fluctuates by 2.3-fold and KS by 1. 7-fold. The
      large discrepancies reflected in the expressed protein have accrued within a
      single lineage and the implication is that divergence dates of different genera
      based on amino acid sequences, even with well-studied proteins of reasonable
      size, can be wrong by a factor well in excess of 2.

PMID- 9608057
TI  - The evolution of MHC diversity by segmental duplication and transposition of
      retroelements 

PMID- 9608058
TI  - [Body composition and osteoporosis].

PMID- 9608059
TI  - [The role of clinical autopsy in monitoring the quality of the clinical diagnosis
      in an emergency department].
AB  - OBJECTIVE: A total of 61 autopsies performed in patients died in emergency
      department of a university hospital were retrospectively analysed and the
      findings were compared with clinical diagnoses. METHODS: Sensitivity and
      specificity of the clinical diagnoses and the correction of medical procedures
      were measured. The influence of age and sex of patients was analyzed using
      Fisher's exact test and chi-square-test. RESULTS: The most common causes of death
      were cardiovascular diseases (52.46%). Autopsy showed unexpected major findings
      in 44.26% of cases. Major discrepancies between the autopsy reports and the
      clinical diagnoses, were present in 26.22% of all cases. Absolute concordance
      between clinical and autopsy diagnoses was obtained in 44.26% of cases. The major
      sensitivity of clinical diagnosis was found in cerebrovascular disorders (100%),
      upper digestive hemorrhage (100%), and acute myocardial infarction (82.35%). The
      lowest sensitivity was found in malignant tumors (16.66%), hemorrhagic
      pancreatitis (0%) and bowel infarction (0%). The patient cares were correct in
      68.85% of cases. No statistically significant differences were observed in
      relation to age and sex. CONCLUSIONS: We concluded that autopsy is a useful
      method for evaluate diagnostic procedures and quality of medical cares in
      emergency departments.

PMID- 9608060
TI  - [Diabetes in hemodialysis: study of differential factors].
AB  - OBJECTIVES: In uremic patients with diabetes mellitus, morbi-mortality on
      maintenance hemodialysis is considerably higher than in nondiabetic patients.
      This is mainly due to age, seniority and quality of the hemodialysis therapy,
      nutritional status, plasmatic lipid levels and associated pathology. We compare
      all these factors in the uremic patients under hemodialysis in diabetics and non
      diabetics. METHODS: We have studied 307 uremic patients under hemodialysis
      therapy during 199 and 1996. Sixty of them had been diagnosticated of diabetes
      mellitus (19.6%), 17 were type I (DM-I) and 27 were type II (DM-II). We selected
      two control groups no-diabetics, one for each subgroup of diabetics with similar
      characteristics in age, sex and hemodialysis seniority. The control group for DM
      I were 34 patients and for DM-II were 54 patients. RESULTS: Ideal body weight
      percentage, body mass index, mid-arm muscle circumference percentil, serum
      albumin and prealbumin are subnormal for DM-I. By considering whole nutritional
      date, a moderate to severe malnutrition was observed in 79% of DM-I patients,
      50.4% of all non diabetics and only in 30.6% of patients included in the DM-II
      group. However, DM-II patients present hypertrigliceridemia and a decrease in HDL
      cholesterol and apolipoprotein A levels with a high atherogenic index.
      Significantly higher rates of associated pathology were observed among both types
      of diabetic patients than their control groups and especially referred to
      cardiovascular and neurological diseases. CONCLUSIONS: In conclusion, diabetes
      mellitus is an increasing incidence pathology in hemodialysis programs, that is
      associated to a higher morbi-mortality because vascular disease. Undernutrition
      is the main factor in DM-II whereas hyperlipidemia is in DM-II.

PMID- 9608061
TI  - [Serum levels of soluble interleukin-2 receptor in alcoholic patients].
AB  - OBJECTIVES: Contribution of cellular immunity to the onset and perpetuation of
      alcohol-induced liver damage remains controversial. The aim of this work was to
      know whether T-cells participate in the pathogenesis of alcoholic liver injury by
      measuring the serum levels of sIL-2R in alcoholic patients with different degree
      of hepatic damage. PATIENTS AND METHODS: Fifty two patients and eighteen healthy
      subjects (Control group) were included. All patients were active drinkers of at
      least 100 grams/day of ethanol over a ten-years period. Serum sIL-2R was
      determined by ELISA. Liver biopsy was performed in all patients and liver
      function tests, serum immunoglobulins and complement proteins C3 and C4 were
      measured in all participants. The relationship between the sIL-2R and the
      severity of liver disease was studied. RESULTS: Circulating sIL-2R was higher in
      the group of patients than in the control (2.388 +/- 275.7 U/ml vs. 795.7 +/-
      48.7 IU/mL; p < 0.001). There were not increased circulating sIL2R in those
      patients with alcoholic hepatitis. However, patients with cirrhosis showed
      increased serum sIL-2R regardless of the presence of alcoholic hepatitis.
      Furthermore, serum levels of sIL-2R inversely correlated with hepatic function
      test (r = -0.69; p < 0.001 for serum albumin; and r = -0.73; p < 0.001 for the
      prothrombin time) and were highest in those patients of the Child-Turcotte's
      class C. CONCLUSIONS: Circulating sIL-2R increases in alcoholic cirrhosis.
      However, our data do not support a contributory role of the cellular immunity, as
      assessed by circulating sIL-2R levels to the alcoholic liver damage. The
      increased serum sIL-2R in cirrhosis may result from defective heptic clearance of
      this molecule.

PMID- 9608062
TI  - [Abbreviations or acronyms in the internal medicine discharge reports. Study
      Group of the Quality of Information in Internal Medicine (Castilla-La Mancha)].
AB  - OBJECTIVES: Quality of discharge reports is very important for an adequate health
      care activity. Clinical data of these reports must be comprehensible by patients
      and in the different levels of Health Services. Presence of abbreviations causes
      severe shortcomings in the clinical data of these records. METHODS: We analyzed
      the presence of abbreviations in the Internal Medicine discharge reports of 7
      hospitals of Castilla-La Mancha in the year 1992. We evaluated 835 discharge
      reports. RESULTS: Abbreviations were found in personal background 72.4%, present
      disease 31%, physical examination 87.2%, clinical judgement 39.4%, complementary
      explorations 95.8%, evolution 61.4% and treatment-follow up after discharge
      67.4%. CONCLUSION: These results indicate that abbreviations must be avoided in
      discharge reports in order to obtain a better communication between patient and
      doctor and between medical personnel.

PMID- 9608063
TI  - [Mortality in an internal medicine department within a third-level hospital;
      twenty years experience].
AB  - OBJECTIVES: To know and to analyze the main causes of death in an Internal
      Medicine Department (IM) and the mortality rate in such a Department. MATERIALS
      AND METHODS: From 1977 to 1996, a total of 77,310 patients were attended in the
      service under analysis. There were a total of 4,720 deaths. Clinical and
      epidemiological variables were analyzed so do management parameters related to
      inpatient deaths. RESULTS: Global mortality rate was 6.1%; the number of
      admissions increased along the study, whereas mortality rate tended to decrease.
      Median age was 72.8 years in death patients, and this age tended to increase
      during the period of study. Women's age was greater than men's one. The causes of
      the demise were cardiovascular (stroke and cardiopathy), neoplasm and respiratory
      disease, in that order. Neoplastic diseases were the leading death cause in men
      as they were in patients younger than 65 years-old, and AIDS was the main reason
      of death in patients younger than 35 years. Finally, 28.7% who died had been
      inpatients for no more than 48 hours. CONCLUSIONS: We can conclude that deaths in
      our IM department affect, as a rule, elderly patients with cardiovascular or
      neoplastic disease. Moreover, AIDS has experienced an increasing frequency, so it
      had became the first cause of death in patients under the age of 35. The old age
      of patients who die in our service, the great percentage of early deaths and the
      fact that the motive was, in the majority of the patients, a terminal disease,
      support the idea that new social customs tend to remove illness and death from
      family home, approving demise as a hospital event.

PMID- 9608064
TI  - [Necrotizing sarcoid granulomatosis: a case report and review of the literature].
AB  - A patient with asymptomatic necrotizing sarcoid granulomatosis is reported. There
      were bilateral nodules in the chest radiograph but no mediastinal adenopathies
      were seen on a computed tomography scan. The transbronchial biopsy specimens
      under fluoroscopy guidance achieved the diagnosis. Steroid treatment was started.
      The nodules disappeared in three months and reappeared two months later when the
      patient decided to stop treatment. After two years of follow up the nodules
      disappeared spontaneously. This is a rare and seldom reported entity, considered
      by some authors as being and atypical form of sarcoid.

PMID- 9608065
TI  - [Diagnostic assessment of pseudothrombophlebitis syndrome. A report of three
      cases].
AB  - The pseudothrombophlebitis syndrome is a complication of ruptured or dissecting
      synovial cyst in the knee joint (Baker's cyst). Three cases are reported of this
      clinical entity characterized by symptoms and signs suggesting deep vein
      thrombophlebitis. We mainly discuss the clinicoradiological aspects.

PMID- 9608066
TI  - [Atypical presentation and diagnosis of a case of Gitelman syndrome in the adult.
      How to distinguish between Bartter syndrome?].
AB  - We described the case of a patient with 43 year-old, with Gitelman syndrome. The
      patient presented two epileptic crisis. The cranial computerized axial tomography
      (CT) was normal. In the seric and urinary analytic we found hypomagnesemia and
      hypermagnesuria with hypocalciuria. The patient was admitted in our Hospital, and
      with the administration of magnesium, the seric levels increased and the patient
      remained asymptomatic. In this article we describe the diagnosis of this
      infrequent disease, and the differential diagnosis with Bartter syndrome.

PMID- 9608067
TI  - [Non-tropical pyomyositis: review of a case].
AB  - The pyomyositis is still being a rare disease in our environment. A review of
      this illness is made as a result of a new case, which shows some peculiarities
      that differ it from others published previously: the patient showed a basic
      medullary carcynoma of thyroid with cerebral metastasis and the responsible germ
      was a Streptococcus pneumoniae. The immunodepressor factors which are presented
      at most patients who suffer a pyomyositis, the clinic picture so suggestive and
      the image methods we dispose nowadays, should serve to suspect its diagnostic in
      an earlier way, proceeding to its bacteriological confirmation before illness
      evolves to stages as advanced as in the shown case.

PMID- 9608068
TI  - [Cyclosporine in inflammatory bowel disease].
AB  - Inflammatory Bowel Disease (IBD), as Ulcerative Colitis (UC) as well as Crohn's
      Disease (CD), can appear as severe outbreak resistant to steroid treatment. These
      cases require surgery or immunosupressive therapy (mercaptopurine or
      azathioprine). Cyclosporine A (CYA) is a selective, reversible immunosupressor of
      the T helper lymphocites, used in the treatment of organ transplants and in
      certain autoimmune diseases. CYA is not a first line therapy for IBD. In spite of
      the positive results obtained in some uncontrolled studies, only one randomized
      trial has shown the superiority of CYA over the placebo in the treatment of UC
      and avoided colectomy in one third of the patients with the severe form of this
      disease. It can also contribute to the healing of resistault CD fistulaes. The
      potential toxicity of CYA and the few controlled clinical trials limit its use.
      However CYA needs to define its role in the treatment of IBD through II more
      controlled trials.

PMID- 9608069
TI  - [Radiation induced tumors].
AB  - Radiations at cellular level produce different effects, depending on type of
      radiation and irradiated tissue. The radiation-induced cancers are associated to
      non-letals genetics mutations, and to classify like radiation induced tumors is
      necessary that appear in the treatment volume, a long latency period (years),
      histolo-different to the primary lesion, enough doses quantitatively and that
      exists a greater incidence in the irradiated populations. The genetics mutations
      affect at tumoral suppressors gen(Gen RB I, p53, BRCA I, BRCA 2) and repressors
      gen (hMSH 2, hMLH I,...), they could be longer and multifocals mutations, and
      produce lack of cellular control and a greater predisposition to develop tumors
      and a probable risk of increment of radiosensitivity. We present some of the more
      representatives studies about radiation-induced tumors.

PMID- 9608070
TI  - [Bronchiolitis obliterans and bronchiolitis obliterans with organizing
      pneumonia].

PMID- 9608071
TI  - [Ischemic stroke, atrial septal aneurysm and transesophageal echocardiography].

PMID- 9608072
TI  - [Pulmonary lymphangitis, an infrequent manifestation of prostatic
      adenocarcinoma].

PMID- 9608073
TI  - [CA-125 in the diagnosis and monitoring of breast cancer].

PMID- 9608074
TI  - [Primary adrenal lymphoma].

PMID- 9608075
TI  - [Primary adrenal lymphoma].

PMID- 9608076
TI  - [Inferior vena cava thrombosis and adult respiratory distress].

PMID- 9608077
TI  - [Radicular compression by brucellar epidural abscess].

PMID- 9608078
TI  - [Gastrointestinal affectation in xanthogranulomatous pyelonephritis].

PMID- 9608079
TI  - [Cocaine intoxication and acute pulmonary edema].

PMID- 9608080
TI  - [Eating disorders in adolescents. An epidemic?].

PMID- 9608081
TI  - [Analysis of a survey on early detection of hearing loss in Spain].

PMID- 9608082
TI  - [Pulmonary symptoms of primary immunodeficiency diseases].
AB  - OBJECTIVE: Patients who lack major components of the immune system carry an
      increased risk for severe and recurrent pulmonary infections at those respiratory
      sites were the deficient component would, in the normal state, have its greatest
      concentration. We report different pulmonary manifestations in pediatric patients
      with primary immunodeficiency disease (PID). PATIENTS AND METHODS: We studied 44
      children younger than 14 years old, who were diagnosed of PID in our pediatric
      department between January 1990 and May 1996. RESULTS: Antibody deficiencies were
      the most frequent disorders (27/44; 61.3%) followed by PID associated with or
      secondary to other disorders (10/44; 22.7%) and defects of phagocyte function
      (5/44; 11.3%). Twenty-seven patients (61.3%) showed relevant pulmonary
      manifestations that required assistance in the division of pediatric pulmonology.
      Bronchial responsiveness was seen in 17/27, 11/27 had recurrent pneumonias with
      development of bronchiectasis in 7/27. Opportunistic or severe pneumonias leading
      to acute respiratory failure were diagnosed in 9/27. Necrotizing pneumonias
      leading to development of pneumatoceles, cavities or abscesses was seen in 3/27
      with the same rate for lymphoid interstitial pneumonia. Respiratory symptoms were
      the first manifestations of PID in 19/27 (70.3%). CONCLUSIONS: The findings of
      the study emphasize the responsibility of the pediatric pulmonologists in
      avoiding the delayed diagnosis of PID since the prognosis depends on the
      precocity of diagnosis.

PMID- 9608083
TI  - [Medical responsibilities concerning maternal breast-feeding].
AB  - OBJECTIVE: The objective of this study was to determine the knowledge of high
      ranking officers in Servei-Valencia-Salut (SVS) about breast-feeding (BF) and
      national and international regulation related to it, in addition to determining
      what sanitary policies were undertaken by them to promote BF. PATIENTS AND
      METHODS: A survey was sent by mail to all high ranking officers (HO) of SVS and
      all pediatric chief staff services (PC) in our community. To analyze data between
      both groups a Chi square test and odds ratio in the qualitative variables and
      variance in the quantitative. RESULTS: Of the surveys sent, 100% were answered by
      the PC and 44% the HO. Breast-feeding was ranked as superior to artificial
      feeding by 100% of PC and 73% of HO (p < 0.05). Both groups believed in the
      necessity of carrying out policies to promote BF in developed countries. Only two
      PC seemed to know the 1981 OMS's code. All PC carried out policies of BF
      promotion in their area of influence, while in the HO the percentages varied from
      64% to 0% according to their position in the health service organization.
      CONCLUSIONS: It is necessary to spread the knowledge of and to apply the
      OMS/UNICEF normatives and to involve al HO with real decision-making power in the
      development of sanitary policies.

PMID- 9608084
TI  - [Pulmonary tuberculosis in children: its age-dependent aspects].
AB  - OBJECTIVE: The aim of this study was to investigate the clinical and radiological
      particularities of pulmonary tuberculosis depending on the age of the child.
      PATIENTS AND METHODS: The medical records of all children with pulmonary
      tuberculosis diagnosed between 1985 to 1996 were reviewed. They were divided into
      three age groups according to age: < 3 years, 3-5 year and 6-15 years. RESULTS:
      Of the 173 children identified, 51.4% were male. Forty percent were < 3 years if
      age, 33.1% between 3 and 5 years and 26.1% between 6 and 15 years old. The
      frequency of diagnosis derived from a case contact investigation was higher in
      children < 3 years of age (38.6%) and children aged 3-5 years (52.6%) than in
      children between 6-15 years old (21.7%, p < 0.05 for both). In the other cases,
      diagnosis was the result of investigation of an ill child, investigation of a
      child after pulmonary tuberculosis was diagnosed in a sibling and routine
      tuberculin skin test reactivity. An adult source of tuberculosis was identified
      in 68.6% of the children < 3 years old, 59.6% of children aged 3-5, but only in
      37% of the children aged 6-15 years (p < 0.05 for both). The case contact was a
      family member in 92.7% of the children < 6 years of age and in 66.7% of children
      aged 6-15 years (p < 0.01). Culture of Mycobacterium tuberculosis was positive in
      47.1% of children < 3 years old and 43.9% of children aged 6-15 years, but only
      in 27.5% of children aged 3.5 years (p < 0.05). Pulmonary parenchymal disease was
      more frequently found in children < 3 years (67.5%) than in children aged 6-15
      years (39.4%, p < 0.05). CONCLUSIONS: Investigation of an adult source is
      essential when a child is diagnosed of pulmonary tuberculosis. Pulmonary
      tuberculosis is more intense and the source of adult contact is more frequently
      found in children < 3 years old.

PMID- 9608085
TI  - [Conservative treatment of neurogenic fecal incontinence. Our experience with
      children].
AB  - OBJECTIVE: The objective of this study was to present the use of retrograde colon
      enema in myelodysplasic patients with fecal incontinence. PATIENTS AND METHODS:
      Thirty-three patients, 16 males and 19 females, 5 to 22 years old (average age
      11.9 years) with spina bifida and fecal incontinence which obliged them to use a
      diaper. Retrograde colon enema procedures were performed in all of them. RESULTS:
      With the use of the retrograde enema the best rectal emptying was achieved and
      kept 32 children (97%) diaper free after a follow-up period of more than two
      years. Only one girl (3%) needed pads because she was not able to defecate in an
      appropriate place after administering the enema. CONCLUSIONS: The retrograde
      enema is the best conservative treatment for children with neurogenic fecal
      incontinence. This method achieves good rectal emptying allowing the children to
      be diaper free, resulting in better social adaptation and integration.

PMID- 9608086
TI  - [Spontaneous development of idiopathic short stature. Analysis of a group of 42
      children followed to their final body height].
AB  - Idiopathic short stature is a common pediatric problem that has a heterogeneous
      nature and an unknown outcome concerning adult height (AH). OBJECTIVE: The main
      objective of this study was to assess the spontaneous adult height and the
      influence of several pre and post pubertal predictors over AH. The secondary
      objective was to create an historical control group to compare these patients
      with others that had been treated with growth-promoting therapies. PATIENTS AND
      METHODS: A prospective observational study was made with prepubertal male
      patients who consulted for short stature before 1986 until they reached AH. They
      did not receive any treatment. The data are shown as mean and standard deviation.
      Student's paired t test was used for comparison of groups. Predictive and
      descriptive models over final height were performed with multivariant analysis. A
      "p" value of less than 0.05 was considered statistically significant. RESULTS:
      Data of 42 children was analyzed. Mean age was 10.8 (2.2) years. The standard
      deviation score (SDS) for adult height spontaneously increased in 0.37 +/- 0.24
      (p < 0.05), but it was under target height by 0.59 +/- 0.26 (p = 0.05). Main
      predictors of AH were: initial height, prognosis of AH and initial age (R2 =
      0.58). Final height was no different between children with familial or non
      familial short stature. CONCLUSIONS: This group of children had a mean loss of 4
      cms below their target height. These children may be considered as an historical
      control group to evaluate the treatment with growth-promoting therapies.

PMID- 9608087
TI  - [The development of lipid and anthropometric parameters in the treatment of pre
      pubertal obese patients].
AB  - OBJECTIVE: Relationships have been found between obesity and changes in serum
      lipid levels which may lead to antherogenic lipid profiles. There are few studies
      treating obesity and showing the possibility of improving lipid abnormalities in
      prepubertal obese patients. PATIENTS AND METHODS: One hundred and three obese
      patients ranging from 5.3 to 9.9 years old have been studied. Anthropometric
      (height, weight, body mass index-BMI-, and subscapular and triceps skinfolds) and
      lipid (total and lipoprotein cholesterol, triglycerides, apoprotein A1 and B)
      parameters were measured both at the beginning of the study and after six months
      of diet treatment. Patients were included in three groups according to their
      response to treatment: good response (GR), no response (NR) and bad response
      (BR), if the difference in BMI was less than 1 point (< 1), between -1 and +1 and
      more than 1 point (> 1), respectively. RESULTS: Forty-one patients (39.8%) were
      noncompliant. Of the remaining sixty-two, 41 (66%) had a GR, 16 (25.8% NR and 5
      (8%) BR. The obese patients showed a significantly lower HDL-C (38.8 +/- 15.6 vs
      48.3 +/- 10.2 mg/dl, p < 0.01) in comparison to the control group. GR patients
      showed a statistically significant increase in HDL-C (48.2 +/- 9.1 vs 54.9 +/-
      12.0 mg/dl, p < 0.01) and apoprotein A1 (126.7 +/- 17.3 vs 136.0 +/- 17.4 mg/dl,
      p < 0.05) levels at the end of the study. There was no statistically significant
      difference in serum lipid levels in the other two groups. There was no
      statistically significant correlation between serum lipid levels and
      anthropometric parameters. The difference between final minus initial value in
      both lipid and anthropometric parameters were not correlated. Sixteen patients
      (17.7%) had pathological serum lipid levels, 15 of them showing
      hypertriglyceridemia, that disappeared in GR patients. CONCLUSIONS: Prepubertal
      obese patients show alterations in lipid profiles and this is not correlated with
      anthropometric parameters. The improvement in these anthropometric parameters
      improve the lipid profile. Initial pathologic serum lipid levels in GR patients
      become normalized.

PMID- 9608088
TI  - [Stimulation increase in evoked acoustic otoemissions].
AB  - OBJECTIVE: Evoked otoacoustic emissions (OEAE) are an excellent evaluation method
      of the hearing organ and are principally useful in newborn screening. During the
      performance of this technique, doubtful cases sometimes exist and they are
      customarily considered as failures of the test, increasing the group of children
      to be re-evaluated. The program IL088 has the possibility of increasing the
      stimulus intensity (gain). We applied this gain to all children with doubtful
      OEAE in attempts to give a pass or fail score. PATIENTS AND METHODS: The record
      of OEAE was accomplished with the system IL088 v3.5. It was applied to 70 ears of
      healthy newborns, a gain of +15 dB initially and/or +21 dB (if a pass score was
      not obtained). Some normal ears were included in this group as controls. Of the
      explored ears, 23 had a normal OEAE, 17 presented a doubtful response and in 30
      cases the answers were negative (fail). RESULTS: This study demonstrates that in
      doubtful cases, the usefulness of increasing the gain is very high permitting
      that these cases accomplish pass criteria (15/17). In the ears with a lack of
      response there is an increased response, but it usually does not reach a passing
      level (6/30). In children with normal response the pass rate does not vary.
      CONCLUSIONS: The increase in gain in ears with a doubtful response offers a high
      a rentability, reducing the the initial failure rate of OEAE without altering the
      real failure rate or affecting those that initially pass allowing a reduction in
      the number of second evaluations.

PMID- 9608089
TI  - [Bacterial meningitis. Clinical-epidemiological study. Review of 8 years (1988
      1995)].
AB  - OBJECTIVE: The objective of this study was to determine the epidemiological and
      clinical characteristics of the bacterial meningitis assisted in the Hospital
      Materno-Infantil of Complejo Hospitalario Carlos Haya of Malaga. PATIENTS AND
      METHODS: The epidemiological, clinical, biological and therapeutical aspects are
      analyzed between the period of January 1988 to December 1995. RESULTS: The number
      of cases was 322, with the pathogen known in 240 (74.6%) and undetermined in 82
      cases (24.6%). Meningococcal meningitis was the predominant cause with 162 cases
      (67.5%), followed by Haemophilus influenzae (40 cases, 16.7%) and pneumococcal
      meningitis (27 cases, 11.3%). Neisseria meningitidis type B was the most common
      serogroup, with an increasing number of type C from 1993.

PMID- 9608090
TI  - [Changes in weight, length and head circumference in premature newborn babies
      weighing less than 1,500 grams at birth].
AB  - OBJECTIVE: The objective of this study was to analyze the weight, length and head
      circumference development in prematurely born babies who weighed less than 1,500
      grams and who were included in the follow-up program of our neonatal unit.
      PATIENTS AND METHODS: Review of data of the cohort included in the follow-up
      program between May 1990 and September 1995 was carried out. The weight and
      length were measured from 3 months of corrected age to 4 years of age. The head
      circumference was measured until 2 years of age. RESULTS: We recruited 259
      premature newborns (136 boys and 123 girls). The median gestational age was 30
      weeks (23 to 36) and the median weight was 1,150 g (500 to 1,499 g). Twenty-seven
      percent were underweight for their gestational age (LWGA). The proportion of
      cases with weight below the 3rd percentile in the follow-up was stable around 25%
      in the group of adequate weight for gestational age. (AWGA). At 3 months of
      corrected age this proportion was 70% in the LWGA group, but there was a trend
      towards catch-up at 2 years of age. The worst results were obtained in the group
      that weighed less than 750 g at birth. The head circumference was better
      preserved than longitudinal growth and thus better than weight. All cases of head
      circumference below the 3rd percentile in the follow-up occurs in the LWGA group.
      CONCLUSIONS: Weight was the parameter with the worst evolution during follow-up,
      especially in the group that weighed less than 750 g at birth. The group of LWGA
      tended to catch-up at 2 years of age.

PMID- 9608091
TI  - [Neonatal sepsis caused by Streptococcus agalactiae. What should be done?].
AB  - OBJECTIVE: Within the common pathogenic flora responsible for neonatal sepsis,
      streptococci group B (SGB) is the most frequently found etiological agent. The
      fact that it is a frequent colonizer of the female perigenital area has resulted
      in a whole host of detection and eradication strategies via preventative measures
      applied to the pregnant woman to eliminate vertical transmission to the newborn.
      PATIENTS AND METHODS: We present a revision of SGB sepsis and our protocol based
      on the intrapartum treatment of those pregnant women with risk factors and the
      study in the newborn at risk of infection with early detection of particles of
      Latex in urine for SGB (Slidex Strepto B bioMerieux), as well as the customary
      analytical and bacteriological tests. We have also revised the different
      strategies in medical scientific publications and several neonatal units for the
      management of this infection and compare this with our protocol. RESULTS: During
      the period 1986-1996 the incidence of SGB sepsis was 0.9/1,000 (19 cases), with
      an incidence of neonatal sepsis of 4.08/1,000. The incidence of sepsis caused by
      Streptococcus agalactiae in our environment is low, although it has increased
      from 15.9% to 28% comparing the first five years with the following six years,
      with a fatality rate of 10.5%. We believe that the most effective strategy for
      this problem is intrapartum identification and treatment of the pregnant woman at
      risk and early diagnosis of the newborn resulting from this pregnancy.
      CONCLUSIONS: We based our strategy on two vias, intrapartum treatment of mothers
      included in the high risk infection group and in the neonatal unit by early
      routine detection of SGB in urine. We have obtained a low incidence rate, low
      mortality rate and avoid false negatives of carrier mothers.

PMID- 9608092
TI  - [Brachmann-de-Lange syndrome in our population: clinical and epidemiological
      characteristics].
AB  - INTRODUCTION: We present the study of the clinical and epidemiological
      characteristics of Brachmann-de Lange syndrome in our population. PATIENTS AND
      METHODS: In this study we present the analysis of 13 cases of Brachmann-de Lange
      syndrome identified among 24,696 infants with congenital defects registered by
      the Spanish Collaborative Study of Congenital Malformations (ECEMC) between April
      1976 and June 1996. RESULTS: The minimum estimation of the prevalence in our
      population is 0.97 per 100,000 live births. We have epidemiologically confirmed
      the presence of intrauterine growth retardation and have observed that parental
      ages tend to be relatively young. We have observed a wide range of clinical
      expression of this syndrome. One hundred percent of our cases have limb reduction
      defects, followed in frequency by craniofacial alterations (84.62%), abnormal
      hair distribution (76.92%) and genital defects (69.23%). Upper limbs are
      predominantly affected and one case of diaphragmatic hernia is worth mentioning.
      We underline the importance of the differential diagnosis with Fryns'syndrome.
      CONCLUSIONS: The cases studied correspond to the most severe form of the
      syndrome, reason for which the prevalence is a minimal estimate. However, the
      mild forms of the syndrome are more frequent and it is important to consider that
      the face, especially the form of the eyebrow, could be a good guide for the
      diagnosis of mild forms of the syndrome.

PMID- 9608093
TI  - [Clinical variability of chondrodysplasia punctata].

PMID- 9608095
TI  - [Waardenburg syndrome and Hirschsprung disease].

PMID- 9608094
TI  - [Kaposi's varicella-like eruptions in two patients with atopic dermatitis].

PMID- 9608096
TI  - [Terminal 1q deletion by translocation t(1;20)pat, confirmed by in situ
      hybridization].

PMID- 9608097
TI  - [Perforant elastosis serpiginosa associated with Down's syndrome. Report of 2
      cases].

PMID- 9608098
TI  - [Subdural empyema: a complication of sinusitis. Report of 3 cases].

PMID- 9608099
TI  - [Neurocutaneous melanosis and Dandy Walker syndrome].

PMID- 9608100
TI  - [Rubinstein-Taybi syndrome associated with hypoplasia of an extremity. A report
      of a neonatal case].

PMID- 9608101
TI  - [What is your diagnosis? Acute scrotal syndrome in a newborn].

PMID- 9608102
TI  - [Controversies over the treatment of obesity].

PMID- 9608103
TI  - [Inappropriate hospitalization according to the Pediatric Appropriateness
      Evaluation Protocol. A study of Spanish pediatric services].

PMID- 9608104
TI  - [Nodules precipitated by methotrexate in chronic juvenile polyarticular
      arthritis].

PMID- 9608105
TI  - [Why not allocate 7% of the budget of our congresses to the cooperation for
      development?].

PMID- 9608106
TI  - [Hafnia alvei in acute gastroenteritis in children].

PMID- 9608107
TI  - [Epidemiologic study on cardio-respiratory arrest in children. Spanish Neonatal
      and Pediatric Cardiopulmonary Resuscitation Group].

PMID- 9608108
TI  - [Acute viral myositis. Is etiologic confirmation necessary?].

PMID- 9608109
TI  - [The adviser on drugs in primary care].

PMID- 9608110
TI  - [Prevalence of mental diseases in women of an urban area].
AB  - OBJECTIVES: The main aim was to calculate the prevalence of mental pathology in
      women between 18 and 70 in a Health District of Pamplona; second, to describe
      comorbidity and to analyse how mental pathology was recorded in the clinical
      histories. DESIGN: An observational crossover study with randomised selection.
      SETTING: A community study in the Txantrea quarter of Pamplona, covering 21,590
      inhabitants, with 7605 women between 18 and 70. PATIENTS: Randomised sample,
      stratified by age, of 237 women between 18 and 70 taken from the 1991 Census.
      MEASUREMENTS AND RESULTS: In a face-to-face interview at the Health Centre, the
      DIS Questionnaire, which diagnoses mental illness, was administered to all
      participants. A check was made to see if mental pathology was recorded in their
      clinical history. The prevalence of mental illnesses, mainly Phobias and
      Depression, in the "last year of life" was 33.3% (27.5-39.5), which fell to 24.9%
      (19.7-30.7) when tobacco abuse was excluded. The most common pathologies were:
      Depression (17.3%), Tobacco dependency (17.3%), simple Phobia (14.8%),
      Agoraphobia (13.5%), social Phobia (8.9%) and post-traumatic stress (8.0%).
      CONCLUSIONS: Understanding the high psychological morbidity in these urban women
      can contribute to the development of Mental Health Promotion and Prevention
      Programmes and foment fuller mental health training for Primary Care
      professionals.

PMID- 9608111
TI  - [30 cases of strongyloidiasis at a primary care center: characteristics and
      possible complications].
AB  - OBJECTIVE: To study the characteristics of the Strongyloides stercoralis
      infestation in our area. DESIGN: A 30-case series. Survey of workplace behaviour
      and hygienic conditions in the home. Review of clinical histories to check for
      factors putting subjects at risk of severe self-infection. SETTING: 21,000
      inhabitants covered by the Oliva Health Centre. PATIENTS: All the cases diagnosed
      between January 1994 and June 1997. MEASUREMENTS AND INTERVENTIONS: The diagnosis
      was carried out by observing under the microscope both fresh Strongyloides
      stercoralis larvae and cultures of three serial faecal samples. RESULTS: We found
      19 men (63.3%) and 11 women (36.7%), with an average age of 65 (SD, 11.5 years).
      28 had been born in the area (93.4%). 15 had never travelled abroad (50%). Of the
      19 men, 18 (94%) had done agricultural work barefoot, but none of the women.
      Clinically, 17 (56.6%) had chronic symptoms; cough was the most common, in 12
      (40%). CONCLUSION: Incidence in our area of Strongyloidiasis, although diagnosed
      infrequently, has increased considerably with the systematic discarding of the
      infection in non-attributable cases of Eosinophilia.

PMID- 9608112
TI  - [Social determinants of family cohesion and adaptability].
AB  - OBJECTIVE: Evaluation of social determinants which are characteristics of
      balanced (functional) and extreme (dysfunctional) families regarding cohesion and
      flexibility dimensions. DESIGN: Observational, randomised survey. SETTING: Dr.
      Jose Castro Villagrana Primary Care Centre, Health Ministry, Mexico. PATIENTS:
      270 randomised families of Tlalpan, Mexico City, who answered FACES III.
      MEASUREMENTS AND RESULTS: Using discriminant analysis statistical technique, 15
      independent variables (social, demographic and familiar determinants) and two
      dependent variables (balanced and extreme types of families) were analysed and
      related with cohesion and adaptability dimensions. CONCLUSION: There is
      accordance of these results with others which were obtained using different
      family assessment instruments like Family Apgar. However using FACES III and
      Circumplex Model the analysis of variable's interaction were possible.

PMID- 9608113
TI  - [Youth studying at universities: their sexual and reproductive health].
AB  - OBJECTIVE: We intend to know the sexual and contraceptive behaviours of the
      youth. DESIGN: Transverse descriptive study based on a structured, anonymous and
      self-administered questionnaire. SETTING: South University of Galician (Ourense
      Campus). PARTICIPANTS: 304 universities of 1st course, in 1996-1997, that were
      selected at random according to studies that they were making. MEASUREMENTS AND
      RESULTS: We analyse the age, sex and sexual and contraceptive behaviour, with the
      statistic programme SPSS. The 63.49% is women and the average age is 19.46 +/-
      1.55 years. The 51.77% began to masturbate between the 11 and 14 years, and they
      do it of 1 at 2 times/week. The 2.34% and the 4.09% have homosexual and bisexual
      experiences, respectively. The 57.4% hasn't began the coitus. The 56.15% of whom
      had sexual experience it was begun between the 17 and 19 years. CONCLUSIONS:
      Through individual/couple consultation and/or work in little groups, is necessary
      to make Sexual Health Promotion and Sexual Risk Prevention.

PMID- 9608114
TI  - [Extrapyramidal toxicity caused by metoclopramide and clebopride: study of
      voluntary notifications of adverse effects to the Spanish Drug Surveillance
      System].
AB  - OBJECTIVE: To clarify if there is any basis for the hypothesis that Clebopride
      leads to more extrapyramidal reactions than Metoclopramide. DESIGN:
      Observational, longitudinal, retrospective and comparative study of two series of
      cases. SETTING: The entire Spanish healthcare system. PATIENTS: Those notified to
      the Spanish Drug watch system as possibly having suffered an adverse reaction to
      Metoclopramide (n = 98) or Clebopride (n = 123) between 1/1/1990 and 10/6/1997.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: 84.3% of suspected adverse
      reactions to Clebopride and 51.6% of those to Metoclopramide had a non-hospital
      precedence (P < 0.001). In 48.0% of suspected adverse reactions to Metoclopramide
      and 72.4% of those to Clebopride, there was extrapyramidal toxicity (P = 0.021).
      CONCLUSIONS: There is a basis for the hypothesis that Clebopride causes more
      extrapyramidal reactions than Metoclopramide. It was reasonable to realize a
      study based on this hypothesis.

PMID- 9608115
TI  - [A descriptive study of pediatric dermatologic diseases diagnosed at the Manises
      Health Center over 1 year].
AB  - OBJECTIVE: To determine the frequency and types of paediatric dermatological
      pathologies diagnosed at a Primary Care Centre, and the referrals for them to
      specialists. DESIGN: Descriptive study. SETTING: Primary Care Paediatrics clinic
      at the Manises Health Centre, Valencia. PATIENTS: Children under 14 attending the
      clinic during 1995. MEASUREMENTS AND RESULTS: The diagnostic groups were: skin
      infections, Dermatitis-Eczema, Urticaria-Erythema, Zoonosis, hair and nail
      disorders, pigmentation disorders and miscellaneous. Age groups were: under one,
      from 1 to 4, from 5 to 9 and from 10 to 13. Referrals were to the Specialist
      Centre and to the hospital. There were 1309 first dermatological consultations
      (5.91% if all paediatric consultations). 38.20% were for skin infections; 25.67%
      for Dermatitis; 17.11% for Urticarias; 8.33% for Zoonosis; 4.89% for disorders of
      hair and nail; 1.83% for pigmentation disorders; and the remaining 3.97%
      miscellaneous. 160 (12.22%) were referred to specialists. CONCLUSIONS: There is a
      great deal of dermatological pathology in non-hospital paediatric clinics. Over
      90% of this pathology is in one of the first five groups above.

PMID- 9608116
TI  - [Ambulatory therapeutic noncompliance of the aged treated with digoxin].
AB  - OBJECTIVE: To quantify the percentage of out-patient doses (OPD) of Digoxin taken
      by elderly people in treatment. DESIGN: An observational, longitudinal and
      retrospective study. SETTING: Out-patient clinics at a geriatric hospital.
      PATIENTS: 67 patients were treated orally with Digoxin: 39 women; age 79 +/- 6;
      ideal weight, 55.7 Kg +/- 7.1; plasma creatinine, 1.3 +/- 0.9 mg/dl; in-hospital
      dose 3247.6 +/- 1309.4 ng/Kg; out-patient dose, 3205.7 +/- 1359.9 ng/Kg. They had
      two consecutive Digoxinemias, one in and one out of hospital, with an interval of
      1 to 18 months between them. MEASUREMENTS AND MAIN RESULTS: Therapeutic
      compliance was calculated by comparing the Digoxinemia/dose relationship per Kg
      of the ideal in-hospital weight against the non-hospital one. 37.3% of the
      patients ingested 80 to 110% of the OPD (95% CI, 26.7%-49.3%). The 36 patients on
      a constant dosage took 74.3% +/- 34.1% of the OPD, whereas the 31 not on a daily
      dose took 87.7% +/- 25.3% (P < 0.07). CONCLUSIONS: Non-compliance is common and
      hard to detect clinically. Therefore, it is dangerous to adjust the dose of non
      compliant patients only on the basis of Digoxinemias or effects of the medicine,
      or on the doctor's view about compliance.

PMID- 9608117
TI  - [How to elaborate a health project in a needy country].

PMID- 9608118
TI  - [Antibiotics policy in primary care. Practical experience in a health district.
      Primary Care Antibiotics Commission of the Mallorca Area].

PMID- 9608119
TI  - [Models of community participation in health care in the context of the health
      marketplace: the myth of the consumer].

PMID- 9608120
TI  - [A new possibility of health education: in the free time].

PMID- 9608121
TI  - [Uniformity requisites for manuscripts submitted for publication in biomedical
      journals. International Committee of Medical Journal Editors].

PMID- 9608122
TI  - [Referral of patients to a hospital emergency service].

PMID- 9608124
TI  - [Are we the family physicians the only ones responsible for signing people on and
      off work?].

PMID- 9608123
TI  - [Record of a practical training: students give their opinions].

PMID- 9608125
TI  - [Concerning the congresses].

PMID- 9608126
TI  - [Health education].

PMID- 9608127
TI  - [Health education yes, perversions no. Author's reply].

PMID- 9608128
TI  - [Academic recognition of family medicine by the university cannot be put off any
      longer].

PMID- 9608129
TI  - [Spanish version of ECBI (Eyberg Child Behavior Inventory): measurement of
      validity].
AB  - OBJECTIVES: To translate into Castilian (Spanish) and measure the validity of the
      ECBI (Eyberg Child Behaviour Inventory), a questionnaire to screen behavioural
      disorders in pre-school children. DESIGN: Translation and back-translation of the
      ECBI. A descriptive crossover study. SETTING: Primary Care Paediatrics. PATIENTS:
      All the 3, 4 and 5-year olds from 4 paediatric clinics at 4 Health Centres (n =
      527). One refusal. MEASUREMENTS AND MAIN RESULTS: The questionnaire was filled in
      by the children's mothers and was repeated 20 days afterwards for 35 children.
      High coefficients of internal consistency (Cronbach's alpha = 0.87) and stability
      (intragroup correlation = 0.89 [0.78-0.94]) were obtained. There was good
      factorial validity, as 84% of the variance was explained by the four factors with
      value greater than 1. CONCLUSIONS: The Spanish version of the ECBI is a brief and
      easy questionnaire with good results in psychometric assessment. Therefore, it
      can be recommended for use in paediatric Primary Care in order to detect children
      with behavioural problems.

PMID- 9608130
TI  - [Use of reagent materials for self-monitoring in the metropolitan area of Malaga
      (1994-1996)].
AB  - OBJECTIVES: To find the evolution of consumption of self-analysis material used
      to control Diabetes (reactive strips of glucose) and the costs involved, in the
      metropolitan area of Malaga from July 1994 to the first quarter of 1996. DESIGN:
      Descriptive retrospective study. SETTING: Metropolitan area of Malaga (580, 586
      inhabitants), which is divided in two HEALTH DISTRICTS: Malaga East and West.
      PATIENTS: All diabetics using reactive strips in the metropolitan area of Malaga
      which are charged to the National Health system. MEASUREMENTS AND MAIN RESULTS:
      The data base of the health districts of the metropolitan area of Malaga was used
      for the review of public prescriptions of reactive strips. Consumption in
      relation to the total population was analysed and the average consumption per
      diabetic was calculated. The total number of patients for whom reactive strips
      were prescribed increased considerably over the three years studied. CONCLUSIONS:
      A considerable increase in consumption of glucose reactive strips was observed in
      recent years in the metropolitan area of Malaga, mainly because of its
      generalised use among elderly patients. Consumption of urine strips was small and
      tended to fall.

PMID- 9608131
TI  - [Attitudes and knowledge of primary care physicians about community breast cancer
      screening programs].
AB  - OBJECTIVE: To find the view of Primary Care doctors in relation to the need for a
      community programme of breast cancer screening, its effectiveness and the
      criteria underlying its application. DESIGN: Crossover study. SETTING: Municipal
      districts of Ciutat Vella and Sant Marti, Barcelona. PARTICIPANTS: General
      Practitioners (GPs) in the programme. INTERVENTION: A self-filled questionnaire.
      The questions sought the level of agreement with 11 statements concerning:
      importance as health problem, effectiveness of the programmes, target population
      and role of GP. Results were compared for: year of graduation, sex and type of
      centre. MEASUREMENTS AND MAIN RESULTS: Of 140 doctors, 110 (78.6%) replied. There
      was majority agreement with all the statements, especially so in: "Breast cancer
      is one of the three main causes of death in women in Barcelona"; "screening of 50
      64-year old women should be recommended"; and "GPs must recommend screening to
      their patients". CONCLUSION: The replies to the questionnaire indicated agreement
      with the programme's basic orientation, except for including 40 to 49-year old
      women in the programme, which the programme did not propose. Hopefully, this
      consensus will help Primary Care professionals become involved in the screening
      programme.

PMID- 9608132
TI  - [Social resources of persons over 60 years of age. Its relationship with
      sociodemographic and health factors (ANCO project)].
AB  - OBJECTIVE: To evaluate the social situation of the over-60s and its relationship
      with several social, demographic and health variables. DESIGN: A descriptive,
      crossover study. SETTING: City of Cordoba. PARTICIPANTS: Systematic random
      sampling of the non-institutionalised population over 60 obtained 1,103 subjects
      (N = 49,674). MEASUREMENTS AND MAIN RESULTS: The multidimensional OARS-MFAQ-VE
      questionnaire was filled in during face-to-face home interviews. The part of the
      questionnaire evaluating social resources (SR) was analysed, extracting
      information on the quantitative, emotional and material support factors. The
      subjects were classified into three groups by their social situation. 14.1% (CI =
      12.7-16.4) lived alone and 7.2% (CI = 5.8-8.9) thought that they would not have
      help available in case of illness or incapacity. CONCLUSIONS: The present study
      described the social situation of our elderly people and found a considerable
      number suffering serious to absolute deterioration. The role of the spouse, the
      children or some friend or trusted person is vital for good social support.

PMID- 9608133
TI  - [Evolution of the prevalence of hepatitis A antibody in Seville].
AB  - OBJECTIVE: To find the evolution of the prevalence of the Hepatitis-A antibody in
      Sevilla. DESIGN: Observational study of a crossover type. Comparison of results
      in 1995 with those from a similar study in 1981. SETTING: Health Area covered by
      Sevilla's University Hospital Virgen del Rocio. PATIENTS AND OTHER PARTICIPANTS:
      Aliquots of serum from patients without Hepatitis were obtained from the
      hospital's clinical analysis laboratories. MEASUREMENTS AND MAIN RESULTS: The
      sera were analysed in the Nuclear Medicine laboratory of the HUVR. 37.96% (62.74%
      in 1981) of the individuals surveyed were HA-positive. Prevalence increased with
      age: in the over-24s it was over 75% (90% in 1981). The differences between the
      two sets of results was significant (p < 0.001). CONCLUSIONS: Hepatitis-A
      infection is becoming less common in Andalusia, which can now be considered a low
      incidence area.

PMID- 9608134
TI  - [Use of the ankle/arm index obtained by echo-Doppler as a diagnostic method in
      peripheral arteriopathies in primary care].
AB  - OBJECTIVE: To describe the use of the ankle/arm index obtained by echo-doppler as
      a method of assessing patients with a clinical picture suggesting peripheral
      arteriopathy. SETTING: Sama de Langreo Health Centre (Asturias). PATIENTS: 83
      patients (166 cases) between 23 and 90, who attended for treatment and had a
      possible diagnosis of peripheral arteriopathy. MEASUREMENTS AND MAIN RESULTS: The
      existence of pedal and posterior tibial pulses was explored by echo-doppler; then
      the arm/ankle index was calculated. Data on age, sex and concomitant pathologies
      were collected. The pedal pulse was negative in 11.4%, the posterior tibial in
      9.2%. The arm/ankle index was significantly lower in males (0.86) than in women
      (1.07) (Student's t test 5.11, p < 0.0001). It was lower in diabetics (0.896)
      than in non-diabetics (0.95), but this was not significant (Student's t 0.99, p <
      0.323). CONCLUSIONS: Echo-doppler measurement of the ankle-arm index is confirmed
      as a valid instrument to assist diagnosis and assessment of the severity of
      ischaemia in Primary Care patients whose clinical picture suggests peripheral
      arteriopathy.

PMID- 9608135
TI  - [Evaluation of Spacelabs 90207, the noninvasive automatic monitor for ambulatory
      monitoring of blood pressure].
AB  - OBJECTIVE: To validate a non-invasive apparatus for non-hospital monitoring of
      blood pressure, the Spacelabs 90207 model. DESIGN: A comparative cross-sectional
      study. SETTING: Primary Care. "La Orden" Health Centre in Huelva. PATIENTS: 90
      people, 34 men, of all ages, hypertensive or not and without any treatment for
      Hypertension, and selected at random from the on-demand consulting room.
      MEASUREMENTS AND MAIN RESULTS: Four blood pressure (BP) readings measured with
      the standard manual apparatus (mercury sphygmomanometer) were compared with three
      obtained in sequence with the Spacelabs 90207, validated in line with the
      recommendations of the British Hypertension Society (BHS) and the Association for
      the Advancement of Medical Instrumentation (AAMI). Average age was 51.31 +/-
      16.5, with SP between 102 and 200 mmHg and DP between 60 and 100 mmHg. Means and
      standard deviations of manual and automatic BP readings were worked out: 129.13
      +/- 19 mmHg and 130.50 +/- 19 for SP, and 77.97 +/- 11 and 76.64 +/- 11 for DP.
      CONCLUSIONS: Spacelabs 90207 fulfills the validation criteria of the BHS and
      AAMI.

PMID- 9608136
TI  - [Bronchodilator treatment of COPD].

PMID- 9608137
TI  - [Efficacy of a clinical interview training technique and psychodiagnostic ability
      of the physician].

PMID- 9608138
TI  - [What knowledge do children in Murcia have about organ donation and
      transplantation? A preliminary study].

PMID- 9608139
TI  - [Benign acute myositis in childhood].

PMID- 9608140
TI  - [Alcohol consumption and biochemical tests].

PMID- 9608141
TI  - [The permanence of female circumcision].

PMID- 9608142
TI  - [Ten years of prenatal diagnosis of uropathies. Study and conclusions].
AB  - Since uropathy started to be diagnosed by means of ultrasonography during the
      prenatal period, paediatric urologists have experienced a major increase in
      neonatal consultations, which involve healthy children without any symptoms of
      urinary tract infection. Thereby the criteria for an adequate treatment of these
      uropathies have been modified. With our study, we intend to analyse the changes
      regarding the management of such cases in our Service for the last 10 years. 294
      cases prenatally diagnosed and confirmed by means of postnatal sonography have
      been reviewed, taking into account the type of explorations carried out in order
      to obtain a definitive diagnosis. Ultrasonography, cystourethrography,
      pyelography, scintigraphy and isotopic renography have determined both degree of
      obstruction and the renal function of the patient so as to value the kidney
      viability. We have found 169 cases of pelviureteral junction (PUJ) obstruction,
      52 of vesicoureteral reflux (VUR), 48 of megaureter, 13 of ureterocele, 8 of
      ectopic ureter, 5 of urethral valves, 26 of multicystic dysplasic kidney, 35 of
      renal duplication, 4 of renal cyst, 2 of ectopic kidney, 2 of renal agenesia, 3
      of bladder diverticular, 1 of renal hypoplasia and 1 of Bolande's tumour. 32
      children were operated upon due to PUJ obstruction, 27 due to VUR, 14 megaureter,
      21 due to ureterocele and ectopic ureter, 5 due to valves, 5 multicystic kidneys,
      3 vesical diverticula, 2 renal cysts and 1 due to Bolande's tumour. From a total
      of 367 diagnoses, 109 patients have undergone an operation, which equals a 29.7%.
      The rest of the patients have been subject to a medical follow-up. Only 3
      patients had to be operated on due to an aggravation of their obstruction. To sum
      up, the main advantage of prenatal diagnosis is that it presents the patient
      without urinary infection. Double-diuretic scintigraphy has proved to be the best
      option to explore the obstruction when dilated despite its limitations in the
      case of deficient renal function. The most frequent diagnosis, which has
      undergone a major increase in the last few years, is PUJ obstruction in the
      manner of pyelic dilatation. Many of them are not confirmed postnatally and most
      of them (more than 70%) do not need surgical treatment.

PMID- 9608143
TI  - [Anterior urethral valves].
AB  - The valves of the anterior urethra are a rare congenital malformation, but it can
      cause a significant deterioration of the uppermost urinary system due to their
      obstructive patterns. It's placed fundamentally in the peno-scrotal union or in
      the bulbous urethra. They can associate to the diverticula of the anterior
      urethra. The clinical manifestations can be varied, depending upon the age of the
      child and the degree of obstruction that provoque. The treatment is always
      surgical, although in some occasions they suffice the endoscopic resection. We
      present the 12 cases controlled in our Center, with known ages between 1 month
      and 7 years, that began with tumefaction urethral at micturition in 7 cases,
      urinary infection in 6 and sepsis in 2. All of them required open surgery, after
      the failure of endoscopic resection in one of them. The results have been
      favorable in 9 cases regarding to the repercussions in the renal function. Two
      patients had a need of nephrectomy and one had to be subjected to a renal
      transplantation. The jet at micturition after surgery is good in 10 cases. In
      one, there persists a subtle jet, although without clinical repercussions, and in
      one patient there appeared a slight dilation in the posterior urethra.

PMID- 9608144
TI  - [The usefulness of ultrasonography in the diagnosis of acute appendicitis in
      children].
AB  - The main objective of the present report was the evaluation of the utility of
      echography as a diagnostic method in abdominal pain suspicious of acute
      appendicitis. A control-case study was performed in 165 children hospitalized for
      abdominal pain. Appendicitis histologically confirmed were considered cases (n =
      110) while control (n = 55) were the not-operated patients (46 children) or the
      not-confirmed appendicitis after laparotomy (n = 9). The variables considered
      here were: the results of echography (Eco+ when echography showed signs of acute
      appendicitis: Eco- when not), the age of the patient (randomized at three groups;
      < 6, 6-9, > 9 years), and the conclusions of fisical exploration (conclusive or
      not as acute appendicitis). The results were analyzed statistically with the SPSS
      program, calculating the following predictive values; sensibility, specificity,
      positive predictive value, negative predictive value. Odds Radio before and after
      test and the global value of echography. Authors conclude that ultrasonography as
      method of support to abdominal exploration for diagnostic in acute appendicitis
      is manifest and present a global value of 70.90%.

PMID- 9608145
TI  - [Autologous buccal mucosal graft for urethral reconstruction].
AB  - Proximal hypospadias are a difficult surgical problem, whether it could take
      place different surgical approaches. One of those is based on the creation of a
      neourethra using a free buccal mucosal graft, as a patch or a tube, obtained from
      de lips or cheek. Since 1983 we have been using this technique in 8 patients. The
      urethral meatus was penoscrotal in 3, scrotal in 3 and perineal in 2. There was a
      significant chordee in 3 patients. Hormonal treatment was necessary in 5
      patients. The average age for surgery was 3.5 years. The graft was tubularized in
      all the cases. The free buccal mucosal graft was combined with a distal Duckett
      procedure in 6 patients. Two patients received only a free buccal mucosal graft.
      The final result is satisfactory in all the cases, with a good urinary jet. The
      complications were 7 urethrocutaneous fistulas, 5 of whom needed a surgical
      repair, and 2 stenosis, which also needed surgical repair.

PMID- 9608146
TI  - [Acute abdomen: other initial symptom of abdominal lymphangioma].
AB  - Lymphangiomas are benign tumors, their growth are slow, customarily without
      symptoms, their location more frequent are in head or neck and they're diagnosed
      before the two first life years frequently. Their etiology continues uncertain,
      being accepted the congenital origin. We report on three cases of abdominal
      lymphangioma beginning as an acute abdomen. The importance of these cases is
      based mainly in the low frequency of presentation of these tumors in this
      location (2-5% of the lymphangiomas) and in their initial symptomatology.

PMID- 9608147
TI  - [Gonadal, hormonal and spermatic function in patients treated for
      cryptorchidism].
AB  - This paper studies the gonadal-hormonal and spermatic function of 48 adults (over
      18 years old) who were treated in childhood for cryptorchidism by medical,
      surgical or both treatments. We measure plasmatic levels of FSH, LH, testosterone
      and prolactin of 34 patients and sperm samples of 31 patients. The testicular
      hormonal function was not disturbed except in four patients with high levels of
      prolactin (> 20 ng/ml) without symptoms. The spermatic function was disturbed in
      bilateral cryptorchidism mainly. The better sperm quality and testicular volume
      were at patients treated with hormonal treatment before surgical treatment.

PMID- 9608148
TI  - [Superior vesical fissure].
AB  - Although vesical extrophy is a well-known anomaly, the variants of vesical
      extrophy are exceptional. We present the case of a newborn child, who upon
      exploration, revealed a defect of closure in the infra-umbilical abdominal wall
      through which vesical mucous membrane protruded. A probe introduced into the
      urethra appeared externally at the place of the infraumbilical defect. Following
      the diagnosis of superior vesical fissure, resection of the protruding vesical
      mucous membrane and closure were carried out. The authors reviewed the
      bibliography published in order to study the different kinds of variants of
      vesical extrophy and the associated congenital anomalies. Although these children
      are usually continent, a urodynamic study and a VCU are recommended in order to
      discard the existence of a post closure-uretheral-vesical reflux of the umbilical
      defect.

PMID- 9608149
TI  - [Frontal extranasal glioma].
AB  - Extranasal gliomas are very rare tumours, being difficult to diagnose
      preoperatively due to the unspecific nature of symptoms and, at times, of the
      test. A newborn baby, prenatally diagnosed with frontal tumour, which on
      exploration showed a mass at the root of the nose, red-violet in colour and which
      seemed to become tenser. Skull x-ray and brain ultra-sound were normal. Ultra
      sound of the tumour area and TAC showed a mass with solid content, with possible
      intracraneal communication. Faced with this possibility, removal by neurosurgical
      procedures was performed with no communications with SNC being observed.
      Histological diagnosis: extra-nasal glioma. Tumours situated at the root of the
      nose can have normal skin covering whose aspect is similar to the tumour
      mentioned above. Test carried out may not show accurately whether the tumour
      communicates with SNC or not, which may lead to surgical errors. We recommend
      that these malformations be treated directly by surgical teams which include
      neurosurgical specialists.

PMID- 9608150
TI  - [Postoperative management following single-stage laryngotracheoplasty in acquired
      subglottic stenosis in children].
AB  - Acquired laryngotracheal stenosis (ALTS) in children is a more and more common
      disease, following the widespread adoption of prolonged endotracheal intubation
      for respiratory support, specially among newborn and premature infants with
      respiratory distress syndrome. Several treatment procedures have been described
      in order to solve this problem; some authors have recently reported encouraging
      results with single-stage laryngotracheoplasty, making open reconstruction with
      airway division, cartilage grafts when appropriate, and closure of the
      tracheotomy tract at the same operation, followed by a short period of
      endotracheal intubation, avoiding the need for prolonged laryngeal stenting with
      its associated risks of granulation tissue formation, restenosis and airway
      obstruction, and with no need of new surgical procedures. Two patients of 9 and
      16 months of age underwent successfully the surgical technique described above,
      with no need of laryngeal stent; postoperative management required several issues
      in order to prevent an accidental extubation during the time of scarring of the
      laryngotracheoplasty. No complications occurred. Follow-up at 6 and 12 months
      after operation was normal, both ventilation and voice quality.

PMID- 9608151
TI  - [Electrophysiological correlates of trigger mechanisms of emotional reactions in
      the temporal lobe of the human brain].

PMID- 9608152
TI  - Attention deficits in children with low performance IQ: arguments for right
      hemisphere dysfunction.
AB  - The attentional component of cognitive functioning in children might be viewed
      from several interrelated angles that nearly all point to right hemisphere (RH)
      neural circuits, subserving nonverbal attention. Neuropsychological aspects
      indicative of RH brain dysfunction are one aspect, studied here. Among children
      with learning disabilities (LD) we distinguish between LD with emphasis on
      nonverbal cognitive deficits and LD with verbal dysfunction. We approached this
      dichotomy by studying the extremes of these two LD categories (89 ss) with
      respect to attention deficit disorder with (ADHD) or without hyperactivity (ADD).
      We examined 44 children with at least average verbal IQ (VIQ > or = 95) and lower
      performance IQ (PIQ at least 25 points lower than VIQ), i.e. the nonverbal group,
      and 45 children with at least average performance IQ (PIQ > or = 95) and lower
      verbal IQ (VIQ at least 25 points lower than PIQ). The percentage of AD(H)D among
      the nonverbal LD group was more than twice as high as among the verbal LD group.
      Although a convincing right hemisphere (RH) syndrome could not be shown on a
      neurological basis in most subjects of the non-verbal LD group, a large body of
      evidence points on the one hand to RH dysfunction associated with nonverbal LD
      and on the other hand to an association between RH dysfunction and ADD. However,
      on clinical grounds, discussed here, we consider ADD and low visuospatial
      cognition, being the most important component of low PIQ, as dissociated
      functions, largely subserved by the RH.

PMID- 9608153
TI  - [Components of movement suppression of evoked potentials of the adolescent
      brain].

PMID- 9608154
TI  - [Functional brain asymmetry and principles of organization of speech activity].

PMID- 9608155
TI  - [Functional asymmetry of the brain in sound image lateralization].

PMID- 9608156
TI  - [Features of the lateralization of speech function in stutterers as a function of
      the sex of the subjects].

PMID- 9608157
TI  - [Human discrimination of the rate of motion in the frontal approach of a sound
      source].

PMID- 9608158
TI  - [Features of the variability of the cardiac circadian rhythm under conditions of
      free activity].

PMID- 9608159
TI  - [Hemorheologic profiles in people with normal and elevated arterial pressure].

PMID- 9608160
TI  - [Effect of motor activity on the health of students with different types of
      cerebral interhemispheric interaction].

PMID- 9608161
TI  - [Changes in the interhemispheric functional asymmetry of the brain and parameters
      of professional reliability of operators in the process of work under high neuro
      emotional stress].

PMID- 9608163
TI  - [Integral electromyographic characteristics in patients with diphtheritic
      polyneuropathy].

PMID- 9608162
TI  - [Modeling of the effect of the cerebrospinal fluid in patients with unilateral
      spastic hemiparesis on spinal reflexes].

PMID- 9608164
TI  - [Determination of mass-inertia characteristics of a human leg].

PMID- 9608165
TI  - [Changes in calcium metabolism and its regulation in humans during prolonged
      space flight].

PMID- 9608166
TI  - [Seasonal changes in the blood parameters and kidney function of young and adult
      men at rest and after exposure to water-salt load].

PMID- 9608167
TI  - [Changes in hemocoagulation and fibrinolysis in athletes as a function of
      physical load and increased overall working capacity].

PMID- 9608168
TI  - [Gastric secretion in people of varying body build under conditions of its
      stimulation and inhibition].

PMID- 9608169
TI  - [The effect of heliogeophysical and meterologic factors on the human body].

PMID- 9608170
TI  - [Psychoacoustic testing using computer technology].

PMID- 9608171
TI  - [Circadian and weekly variations in the duration of the individual minute in
      healthy subjects depending on the introversion-extraversion factor].

PMID- 9608172
TI  - [Features of erythrocyte membrane permeability and sorption erythrocyte capacity
      in healthy full-term newborns and their mothers].

PMID- 9608173
TI  - [The 210th anniversary of the publication of the first Russian textbook on human
      physiology].

PMID- 9608174
TI  - [The problem of brain biopotential modifications in endocrine diseases in the
      book of G.M.Frenkel'].

PMID- 9608175
TI  - [Viral genesis and autoimmunity of chronic hepatitis. Suggestion for a
      dynamically descriptive nomenclature without verification of etiology].
AB  - Today, viruses and autoimmunity phenomena are at the focus of interest in chronic
      hepatitis, not least with respect to the differing treatments, e.g. with
      interferon and immunosuppressants. Unfortunately, the last international
      nomenclature fails to take adequate account of the various forms of chronic
      hepatitis, of the fact that autoimmunity phenomena are predominantly
      physiological and also occur in the case of viral hepatitides, and also that the
      cause of autoimmune hepatitis is not clear. If we wish to avoid errors, we should
      employ a descriptive dynamic classification and not forget that the
      reclassification may be needed during the natural history of the disease. The
      indication for treatment should be critically and carefully weighed, and not
      established too hastily. During treatment--in particular with interferon--the
      autoimmunity phenomena should be monitored.

PMID- 9608176
TI  - [Hepatitis overlap syndrome. Working hypothesis or descriptive, concealed
      ignorance?].

PMID- 9608177
TI  - [Allergic rhinitis].
AB  - Allergic rhinitis is the most common of the allergic diseases with, according to
      a number of epidemiological studies, an incidence of about 15% in Central Europe.
      The condition is characterized morphologically by inflammation of the nasal
      mucosa resulting from an IgE-mediated allergic reaction of the immediate type.
      Depending on the allergen involved and the course of the disease several forms of
      allergic rhinitis are distinguished. The present paper describes the
      pathophysiology and clinical symptomatology, current diagnostic approaches and
      the therapeutic possibilities with an eye to their practical relevance.

PMID- 9608178
TI  - [Therapy findings in allergology].

PMID- 9608179
TI  - [Actinic keratoses].

PMID- 9608180
TI  - [Secondary fibromyalgia. Differentiation of primary and secondary fibromyalgia is
      necessary for successful therapy].

PMID- 9608182
TI  - [Managing tinnitus with natural healing. When it whistles and rings in the ear...
      Natural Healing Series, 18: Tinnitus].

PMID- 9608181
TI  - [First aid for mountain climbers with frostbite. Freezing accident at high
      altitude].

PMID- 9608183
TI  - [Impact of the interval between surgery and radiotherapy in the initial phases of
      breast cancer in patients who did not receive systemic adjuvant therapy].
AB  - The purpose was to evaluate the effect of surgery-radiotherapy delay in the
      outcome of patients treated for early breast cancer, who did not receive adjuvant
      systemic therapy. We retrospectively analyzed data from 623 patients with breast
      cancer diagnosis stage I and II and with clinically negative axillary node,
      treated over a 18 year period. Patients were grouped in basis of the delay in the
      beginning of their radiation therapy, after surgery. Group 1 (270 patients) began
      radiation within 4 weeks of surgery, group 2 (285 patients) began 5-8 weeks after
      surgery and group 3 (68 patients) had a delay greater than 9 weeks. Median follow
      up in the total group was 64 months. Patients received a dose of 50-60 Gy to the
      tumor bed and/or 50 Gy to the nodes. Age, menopausal stage, clinical stage of
      disease, histological diagnosis, pathologic tumor size, and nodes metastasis,
      were similarly distributed among the 3 groups. Comparisons of local-control,
      overall 10-year survival and disease free survival curves between the three
      groups were done, no differences were observed among group 1 and 3, showed no
      significant differences in overall survival or local-control, however disease
      free survival was negatively affected by a delay in the administration of
      radiation (p = 0.05). It was concluded that delay in the beginning of radiation
      therapy longer than 8 weeks after surgery in breast cancer stage I and II
      patients treated without systemic therapy, decrease significantly disease free
      survival.

PMID- 9608184
TI  - [Evolution of breast cancer. A 5-year clinical experience at a city hospital].
AB  - In order to clarify the role that some epidemiologic factor might have on the
      clinical evolution of breast cancer, a retrospective study was conducted. Seventy
      six women diagnosed with breast cancer were selected from the population of the
      Hospital de Ginecobstetricia 3 del Centro Medico Nacional "La Raza" del Instituto
      Mexicano del Seguro Social, from 1985 to 1990. Age, medical and family history,
      clinical onset, diagnosis, treatment, evolution and clinical status at present
      were analyzed. Survival analysis and Pearson's correlation were carried out.
      Thirty one percent of the women were 41 to 50 years old, and thirty percent had
      family history of breast cancer. Other systemic condition was present in 42% of
      the patients and multiparity in 12%. The mean age of menopause onset was 47 +/-
      years. Eighty-three percent of the patients looked for medical attention due to a
      mammary tumor mainly in the left breast (75% of the cases). Fifty-one percent of
      the cases were diagnosed in advanced stages. The commonest histologic variety
      found was the invasive ductal carcinoma (94%). Sixty six patients underwent
      surgical therapy. Sixteen percent of the sample had already metastases when
      diagnosed; mainly at lung, bone liver or brain, in that order. Systemic therapy
      was administered in 63% of the cases and radiotherapy in 22 patients. About 48%
      of the whole sample presented recurrency and 24% progression. The overall
      survival at five years was 82%. Sixteen percent of these patients had tumor
      activity clinically apparent. In general, mortality was present in advanced
      stages. Survival analysis demonstrated that age and tumor persistency directly
      influenced survival rate in this population. Other variables' role could not be
      evaluated. Nevertheless variables analyzed are very helpful in actions
      implementation to the breast cancer management.

PMID- 9608185
TI  - [Pattern of wight gain during normal pregnancy].
AB  - The maternal weight gain during pregnancy has been established as a common
      acceptance criterion about 11 Kg., and its evaluation is of interest in
      Gynecology and Obstetrics; the objective of this study was to evaluate the
      Gestational Weight Gain Pattern (GWGP) during the normal pregnancy and its
      association with the maternal height, pregestional weight, Body Mass Index (BMI)
      schooling, the intergensic interval and the newborn weight. It was found through
      a longitudinal and prospective study in women of the urban area, under prenatal
      control in the Instituto Mexicano del Seguro Social (IMSS), in Morelia, Mich.
      Mexico, that the average overall GWGP was of 9.3 Kg, and a normality band within
      6.6 to 12 Kg which is smaller than the established by obstetrics criteria. It was
      not found a correlation between the GWGP and the newborn weight, now that the
      94.3% of them had normal weight. The mother's age, weight, body mass index and
      schooling didn't show any correlation with the maternal weight gain during the
      pregnancy. It was shown that the mother's height and parity influence notably the
      GWGP. It's convenient the adoption during the prenatal control to determine that
      the GWGP normality is in agreement with the bio-psycho-social characteristics of
      the Mexican woman.

PMID- 9608186
TI  - [Epidemiologic evaluation of the diagnosis and treatment of extrauterine
      pregnancy at the ABC Hospital].
AB  - The objective of this study was to determine the frequency, risk factors,
      treatment and morbility of the ectopic pregnancy (EP) at the ABC Hospital. EP
      cases occurring between January 1992 and May 1995 were studied retrospectively
      analyzing the next variables: Number of live births and EP's, the patients age,
      obstetric history, previous EP, sterility, previous pelvic surgeries, gestational
      age at diagnosis, treatment and complications. The results showed that the
      frequency of EP was 2.06% There was a positive correlation between EP and
      infertility, nuliparity, and previous tubal surgery secondary to EP. We concluded
      that even though EP tends to be diagnosed and treated in early stages, the
      majority of the surgical procedures lower patients fertility.

PMID- 9608187
TI  - [Para-tubal cysts: frequency and clinical, ultrasonographic and histological
      correlations].
AB  - We Reviewed 5,100 biopsies, between November 1994 to November 1995 We found 100
      paratubval cysts. The 80% of the cases were surgical findings. The 40% of the
      cases had pain. The 3% of the patients had acute pain, that made necessary an
      urgent surgery. The ultrasonogram revealed an ovarian cyst in 38% of the cases
      and it couldn't detect them in 63% of the cases. The cysts sizes were: 6 cm.
      (84%) *12% 9 between 6-12 cm. and 43% between 12-18 cm. The histopathology report
      was: 57% of serous cyst and 43% simple cyst.

PMID- 9608189
TI  - [Giant mesenchymal tumor of the vulva with atypical clinical evolution].
AB  - Mixed mesenchymal tumors of the vulva are rare lesions. On other hand, aggressive
      angiomyxoma is a recently characterized neoplasm occurring principally in the
      pelvic soft-tissues and showing propensity for local recurrence. The benign soft
      tissue tumors are small than malign neoplasm, mimicking and often are
      misdiagnosed as cysts of Bartholin's gland. In this report we describe one case
      of a benign, giant and atypical mixed mesenchymal tumor of the vulva and its
      particular clinical characteristics.

PMID- 9608188
TI  - [Estrogens of vegetable origin].
AB  - In recent years, estrogens of vegetable origin have acquired some importance that
      justify the presentation of the available data. The compounds that have
      estrogenic effect when ingested as food through vegetables include isoflavones,
      lignines and lactones. The review comprises their chemical structure, metabolism
      and excretion as well as their effect on plasmatic levels of estrogens FSH, LH
      and SHBG as well as their activity over lipoproteins and, naturally, their action
      on menopause symptoms and breast cancer.

PMID- 9608190
TI  - [Reduction of the number of cesarean sections from 28% to 13%: does it reduce or
      increase perinatal maternal mortality: the great doubt?].
AB  - According to the new trends related to decrease the cesarean section rates, we
      conducted our retrospective investigation in order to investigate if the decrease
      of the cesarean section from 28 to 13%, affect the perinatal mortality (before
      labor and during labor) and maternal mortality. The years included in this paper
      were 1990 and 1995. We justified our investigation because some professional in
      health, believe that the decrease of the cesarean section produce an increase of
      the maternal and perinatal mortality. In 1990 and 1995 this were our obstetric
      activity respectively: 1954 and 1504 cesarean section, 4899 and 9176 vaginal
      deliveries, 6893 and 10730 alive newborns, 172 and 199 perinatal deaths, and
      finally 9 and 11 maternal deaths. The comparative statistical analysis is as
      following: for perinatal mortality CHi2 8.00, p 0.004 and OR 1.33 (1.09-1.66) and
      for maternal mortality Chi2 0.34, P 0.56 and OR 1.30 (0.50-3.36). The risk of
      perinatal deaths increased in 1990. In relation to the maternal deaths, the risk
      of mortality didn't increase in 1995.

PMID- 9608191
TI  - [Appendicitis during pregnancy].
AB  - Acute appendicitis es the most common cause of lapparotomy during pregnancy. The
      differential diagnosis in the pregnant woman becomes a challenge due to the
      anatomic changes that take place during the maternal adjustment to pregnancy. We
      have done a retrospective study between january 1989 and december 1994, at
      Instituto Nacional de Perinatologia. We found in that period of time 35,080
      deliveries reported and 4 cases of acute appendicitis during pregnancy. The
      maternal age was between 16 and 42 years old, 26 years in average. Three patients
      were in the 3 trimester at the time of diagnosis, and the most important clinical
      sign was found to be diffuse abdominal pain. In 3 cases diagnosis was attributed
      to obstetric pathology rather than appendicitis in first place. Laparotomy and
      appendicectomy was done to all patients, with on block hysterectomy in only one
      case, having this particular patient an abscess as a postquirurgical
      complication. Just one case reported a healthy newborn delivered at term. It is
      obvious that early diagnosis and quirurgical treatment are important factors for
      the mother and the fetus prognosis. Appendicectomy as well as cholecystectomy are
      the two most common causes of laparotomy during pregnancy.

PMID- 9608192
TI  - [Speciation of metals in occupational medicine].
AB  - The identification and quantification of elements as such (that make up the
      historical analytical method used in toxicological studies) are necessary but not
      sufficient, in all cases, to understand and evaluate the mechanism of interaction
      between elements and biological targets. In fact, in order to approximate the
      factors that control the concentrations of elements in environmental or
      biological media, we need to know the occurrence of species of the elements
      themselves. This is element speciation, i.e. the capability of separating,
      identifying and determining the species in which an element is present and/or
      transformed. There are few, although increasing in latter years, examples of
      element speciation able to confirm the importance of this research approach in
      toxicological studies. Some basic information from these studies have found
      specific application in selecting the most appropriate indicators and the most
      representative matrices for biological monitoring. Furthermore, element
      speciation provides additional and often essential information in evaluating
      metal toxicity. The toxicity of the three oxidation states of Mercury differ
      considerably. For arsenic, a decreasing order of toxicity arsenite > arsenate >
      monomethylarsonic (MMA) > dimethylarsenite (DMA) has been proposed. However, the
      use of speciation in investigating toxicokinetic aspects appears to be difficult
      to apply to many other metals, mainly due to the lack of information about the
      existence and significance of species whose determination would be worthwhile and
      to the lack of analytical methods enabling us to measure species in biological
      media. Nonetheless, the horizon for speciation is more extensive and less linear
      than expected since about 15 elements, 20 oxidation states, and 25 organic
      compounds have been just involved in speciation. Problems might arise for
      biological monitoring practices, and the following topics should be considered:
      (i) identification of species and determination of their concentration; (ii)
      knowledge about the specific (relevant) role in physiologic and pathologic
      processes in which the element is involved; (iii) availability of analytical
      methods responding to acceptable quality requisites; (iv) feasibility and ethics
      of sampling.

PMID- 9608193
TI  - [The educational process of the "competent physician": quality exigencies].
AB  - The spread of Quality concepts and process control in industries and services has
      meant that the educational field has become increasingly affected by the concepts
      of activities optimization and quality assurance. Teaching is comparable to any
      other service supplied in terms of program quality, quality control, quality
      assurance, and quality management. Teaching is a service that can be supplied
      through a number of phases: planning, execution and evaluation or control. This
      paper aims to describe an application of the Quality concept according to ISO
      9000 rules in order to assure quality of teaching and training of the
      occupational physician. The occupational physician is requested to act according
      to particular competencies. This implies the need to meet specific requirements
      (competence-based educational goals). To assure the achievement of these goals,
      the implementation of a teaching Quality system must include: targeting the
      learning objectives (knowledge, skills and attitudes the specialist should have);
      planning the evaluation system (ability of the course to assure the objectives
      are achieved); evaluating the curriculum (relating the acquired competencies to
      the needs). From the integration between Quality concepts and education, new
      rules are arising to comply with the quality needs in teaching, where the quality
      of the teaching program is considered as the suitability of the program to
      satisfy the occupational physician competency needs.

PMID- 9608194
TI  - [Risk evaluation and health surveillance in hospitals: a critical review and
      contributions regarding experience obtained at the S. Gerardo dei Tintori
      Hospital in Monza].
AB  - The incorporation into Italian legislation of the European Community directives
      on the improvement of health and safety at work has promoted a vast effort in
      order to revise the surveillance approach in many facilities, including
      hospitals. At the S. Gerardo Hospital in Monza, the required risk evaluation was
      performed in 1995. The paper here reports the results of environmental and work
      organization inspection, literature review and the proposal of a surveillance
      program. S. Gerardo Hospital is a large facility with 2,547 employees. Major
      structural problems are associated with fire prevention and the continuous change
      required for the development of a modern hospital. Relevant risk in health care
      are: biological risk, in particular hepatitis B and AIDS virus, teratogenic
      viruses (rubella, cytomegalovirus and varicella-zoster) and the renewed
      possibility of tuberculosis infection, often multi-drug resistant; chemical
      hazards, in particular use and exposure to antineoplastic and antiviral agents,
      sterilants like ethylene oxide and formaldheyde; physical risk, well-known for
      ionizing radiations, but important also for non-ionizing radiations; manual
      lifting (patients in particular) which makes nurses one of the occupations most
      affected by low back pain; psycho-social risk, with particular reference to
      stress in emergency departments and everywhere a strong psychological engagement
      is required. Also the risk of non-health personnel, office areas, food
      preparation, housekeeping, maintenance, central supplies and laundry was
      assessed. Health surveillance programs for the exposed and preventive medicine
      programs according international standards for all workers are presented.

PMID- 9608195
TI  - [Pulmonary CO diffusion and radiological findings in subjects formerly exposed to
      asbestos cement].
AB  - A cross-sectional study on 117 male former asbestos-cement workers was performed.
      The aims of the study were: evaluation of the prevalence of respiratory symptoms,
      measurement of pulmonary volumes, flows and DI(co) values, detection of asbestos
      related diseases, and data collection for a medical follow-up of the
      participants. Medical examination included ECSC questionnaire, spirometry, DI(co)
      measurement and chest x-ray. Time since first exposure (latency) and duration of
      employment were used as exposure indices: participants were subdivided into three
      exposure groups, respectively for latency and duration of employment. For
      statistical analysis, multiple linear regression and logistic regression methods
      were applied; significance level was p < 0.05. In 28 participants abnormal DI(co)
      values (< 80% of predicted) were measured, 9 subjects (8%) had radiological
      asbestos-related abnormalities. Lower values of DI(co), after correcting for
      smoking, were observed in the third latency group of subjects; an increased risk
      of radiological asbestos-related abnormalities was observed in relation to the
      duration of employment and latency. This study confirmed DI(co) as an indicator
      of (asbestos-related) pulmonary interstitial disease.

PMID- 9608196
TI  - [Occupational exposure and pollution caused by asbestos during removal work].
AB  - Legislative Decree 277/91 has assigned the Public Prevention Service a
      fundamental role in the provision of information assistance to companies in the
      assessment of work procedures and conditions, in risk evaluation of workplace
      exposure and environmental pollution due to asbestos and in rehabilitating
      reclaimed areas. On the basis of this experience a critical review of attention
      level and prevention strategies can be made so that these relate to the real risk
      in the different kind of reclaiming work.

PMID- 9608197
TI  - [Non-bioavailability of carcinogenic polycyclic aromatic hydrocarbons contained
      in coal dust].
AB  - The aim of the study was to ascertain whether polycyclic aromatic hydrocarbons
      (PAHs) especially 3,4-benzo(a)pyrene, could be eluted from coal dust that comes
      into contact with biological fluids or crosses the skin barrier. A fine-grained
      coal dust with known PAH content was placed into contact with homogenized pig
      lung or human gastric juices, and also applied to monkey skin, using the
      cutaneous window method. The results demonstrate that, in the in vitro systems
      used, PAHs contained in coal dust are not eluted by lung homogenate or gastric
      juices, nor are they capable of crossing the skin barrier. These results justify
      and support the interpretation given to the results of experimental
      carcinogenicity studies on coal dust which never succeeded in demonstrating a
      higher incidence of cancer, particularly lung cancer, in treated animals.

PMID- 9608198
TI  - [Evaluation of carcinogenicity of chemicals and productive processes effected by
      the National Advisory Toxicological Committee].

PMID- 9608199
TI  - [The taxonomic position of nematodes in the genus Trichinella Railliet, 1895].
AB  - In the author's opinion, the recent taxonomic revision of the genus Trichinella
      Railliet, 1895 (Pozio et al., 1992 and others) seems to be hasty and
      insufficiently substantiated. The proposed criteria for identification of new
      species, such as production of new-born larvae (PNBL) by Trichinella females in
      vitro, periods of development of nurse cells (DNC), index of reproductive
      capacity (IRC), resistance to freezing (RF), firstly, have a sufficient
      dispersion and are frequently very close (PNBL) to T. britovi, T. nativa, T.
      nelsoni, and T. pseudospiralis, DNC for these species. Secondly, these criteria
      are not always precise (one cannot agree with the fact that T. spiralis are not
      resistant to freezing). And, finally, it is impossible to be guided seriously by
      such criteria as the low or high significance of IRC or RF. According to the
      fifth criterion--the number of unique allozymic markers--two species are
      obviously distinguished: T. spiralis (6 markers) and T. pseudospiralis (12
      markers). If the absence of capsule formation in case of T. psuedospiralis and
      the participation of birds in the life cycle of this parasite will be added to
      the above-mentioned, two species are again clearly distinguished: T. spiralis and
      T. pseudospiralis. Presently, it is necessary to classify the remaining species
      as varieties of subspecies of T. spiralis and to designate T. spiralis nativa, T.
      spiralis nelsoni, T. spiralis britovi, as recommended by the "Guidelines on
      Surveillance, Prevention, and Control of Trichinellosis" published by the WHO in
      1988.

PMID- 9608200
TI  - [The effect of an invasion by Trichinella spiralis and Trichinella pseudospiralis
      on the ultrastructure of skeletal muscle tissue in the white mouse].
AB  - The ultrastructure of striated muscular tissue was studied in experiments with
      three groups of white mice: those infected with T. spiralis, T. pseudospiralis,
      and in those uninfected (controls). There was a heterogeneity of changes in the
      striated muscular tissue during 35-day infection. Deep damages to the
      contractile, trophic, energetic, supporting, and membranous apparatuses of muscle
      fibers are responsible for subcellular structural changes. At the same time
      compensatory and adaptative processes that reflect the hyperfunction of
      musculoskeletal tissue develop. Generally, T. spiralis causes focal
      ultrastructural changes while T. pseudospiralis induces diffuse ones.

PMID- 9608201
TI  - [The effect of anthelmintics on the serotonin content of cestodes].
AB  - The effects of some anthelminthic agents, such as praziquantel, fenasal,
      albendazole, on the levels of the neurotransmitter serotonin in the tissues of
      Hymenolepis diminuta cestodes and Mesocestoides corti tetrathyridia were examined
      in vivo and in vitro. The finding showed lower serotonin levels in H.diminuta
      after praziquantel and albendazole and in M. corti after fenasal. It is suggested
      that the serotonin neurotransmitter system of helminths is involved in the
      mechanism of action of these agents.

PMID- 9608202
TI  - [Approaches to the combined therapy of helminthiases with leukinferon and
      etiotropic preparations].
AB  - The results of therapy with anthelmintics in combination with leukinferon show
      either higher efficiency of anthelmintics (medamin) or their same efficiency
      (albendazole). The outcomes of combined treatment of infected animals with
      anthelmintics and leukinferon are different and associated with the time of
      leukinferon administration as to the tissue stages of parasitic development, with
      the host's sensitivity and susceptibility to helminth.

PMID- 9608203
TI  - [The effect of leukinferon on the invasive process in experimental
      helminthiases].
AB  - Two models of helminthiases (nippostrongyliasis and trichocephaliasis) were used
      to reveal the therapeutical activity of leukinferon (LF). In experimental
      nippostrongyliasis, the efficacy of LF was similar to that in infected young rats
      and mice whose sensitivity and resistance to infections were different. In the
      model of trichocephaliasis, the therapeutical effect of leukinferon was
      noticeably higher in C57BL/6 mice resistant to T. muris than in sensitive mice
      strains. In intact animals, LF brought about similar lymphocytic prestimulation
      depending on their sensitivity to infection. The infection itself also caused
      increased LF levels comparable to those observed during LF administration to
      intact animals. LF-induced differences in cell prestimulation were especially
      great as infection progressed in animals whose sensitivity to host helminths was
      opposite. The levels of splenocytic LF was higher in resistant hosts (non-inbred
      mice with nippostrongyliasis and C57BL/6 mice with trichocephaliasis) that under
      the similar experimental conditions in animals (rats with nippostrongyliasis and
      DBA/2j mice with trichocephaliasis sensitive to host helminths).

PMID- 9608204
TI  - [An immunochemical study of the antigens from Toxoplasma gondii tachyzoites
      obtained in different cultivation systems].
AB  - The protein composition and immunochemical properties of Toxoplasma gondii
      tachyzoites cultured on Vero cells and on mice were studied. Despite the fact
      that the main components of both preparations were shown to be proteins with
      molecular weights of 47, 34, 24, and 22 kDa, Toxoplasma-infected human sera
      antibodies interact mainly with the antigens of 66, 62, 57, 42, 38, 37, 36, 31,
      and 24 kDa. Comparing efficiency of enzyme immunoassay using the antigens of the
      tachyzoites obtained in different culture systems showed that the preparation of
      cultured Vero cells is similar to those of peritoneal exudates from infected mice
      and may be successfully used for the detection of antitoxoplasma antibodies in
      the sera of infected subjects.

PMID- 9608205
TI  - [The prognosis of the epidemic situation with opisthorchiasis in relation to
      demographic processes in Siberia].

PMID- 9608206
TI  - [Ca++ ion transport blockers as reversants of the drug resistance of malarial
      parasites. 2. The effect of praziquantel on the resistance to chloroquine and
      compound R-70-Zh of Plasmodium berghei].
AB  - The reversing action of anthelminthic praziquantel (P) on the effect of
      chloroquine (C) and compound R-70-Zh (styrylquinazoline) was revealed on a
      Plasmodium berghei model (white inbred mice), using a LNK65 isolate with
      naturally reduced sensitivity to chloroquine and its polyresistant line
      LNK65CHLFR with acquired resistance to chloroquine/fansidar (selected in our
      laboratory). P (125 mg/kg) in combination with C showed a potentiating effect not
      only on the LNK65 isolate, but also on the LNK65CHLFR line, while investigated
      separately on this line, both drugs were not effective in tested doses. Moreover,
      the similar effect of C on the LNK65CHLFR line was achieved in the dose that was
      4 times higher than that of P/C combination. P in a standard dose on the LNK65
      isolate showed a more marked activation of compound R-70-Zh that on C. The
      potentiating effect was manifested in combination with R-70-Zh in the dose half
      as high as that of C; this phenomenon was also reflected by the efficiency index
      (5.0 against the 4.0) accepted in our laboratory and may be associated with the
      higher sensitivity of the LNK65 isolate to R-70-Zh. P showed some antimalarial
      action which manifested itself only by morphological changes on P. berghei
      parasites similar to those observed under the action of some dihydropholate
      reductase inhibitors, such as pyrimethamine.

PMID- 9608207
TI  - [An evaluation of the spectrum of Plasmodium vivax subpopulations by the results
      of an experimental study of late relapses in Delhi].
AB  - The spectrum of Plasmodium vivax subpopulations could be evaluated by analyzing
      the results of experimental studies of late relapses in P. vivax malaria in north
      western Delhi. The spectra of the subpopulations causing late recurrences were
      different for malaria with short-and longterm incubations. The conclusions
      previously made by mathematical stimulation as to that malaria with longterm
      incubation is mainly transmitted at the beginning of the season have been
      confirmed. Based on the results of the frequency analysis, 6 P. vivax
      subpopulations with the values of their development duration of 15, 240, 300,
      390, 720, and 1020 days, respectively, were identified for formalization of an
      epidemic process.

PMID- 9608208
TI  - [An epidemiological analysis of tick-borne borreliosis (Lyme disease) morbidity
      in the Kirovo-Chepetsk District of Kirov Province during 1992-1996].

PMID- 9608209
TI  - [A complex of measures to protect children's groups from attack by blood-sucking
      flies and ticks in the central Ob River valley].

PMID- 9608210
TI  - [African trypanosomiasis (sleeping sickness)].

PMID- 9608211
TI  - [Means for improving the teaching of parasitology in higher medical academic
      institutions].
AB  - In our country's population, the high incidence of parasitoses of various origin
      is largely due to physicians' poor knowledge of parasitology. Information on
      major parasitic diseases, provided to students at all higher medical educational
      establishments, is fragmentary and scarce. For effective preparation of some
      graduates, the Medical Prevention Faculty, Department of Epidemiology, Saint
      Petersburg State Medical Academy, has elaborated a model programme for subsequent
      3-year postgraduate training both of professionally qualified epidemiologists and
      parasitologists (1 year for medical postgraduates and 2 years for junior doctors
      who will specialize in a particular field). This programme provides a
      comprehensive theoretical background, practical skills, and preparation for
      making researches, investigations, and practical work.

PMID- 9608212
TI  - [Tick-borne encephalitis study in the western Urals].

PMID- 9608213
TI  - [The epidemic situation of tick-borne encephalitis and Lyme disease in the city
      of Tomsk].
AB  - Lyme disease and tick-borne encephalitis have similar principal epidemiological
      features chiefly associated with their basic carrier and determinants of human
      infection. The cases of Lyme disease, as evidenced by laboratory studies,
      indicate that there are active natural foci of this infection in the city,
      frequently combining with natural foci of tick-borne encephalitis. At the same
      time a great quantity of cases of tick-borne encephalitis and Lyme disease (mixed
      infection) is notified in Tomsk.

PMID- 9608214
TI  - [The formation of synanthropic foci of trichinelliasis in Vologda Province].

PMID- 9608215
TI  - [Malaria in Ul'yanovsk Province].

PMID- 9608216
TI  - Multiple system atrophy: more on the nature of the beast.

PMID- 9608217
TI  - [Variation of Mini-Mental-State examination scores due to age and educational
      level. Normalized data in the population over 70 years of age in Pamplona].
AB  - The Mini-Mental-State Examination (MMSE) is widely used as a screening tool for
      dementia in epidemiological studies. Its applicability in population-based
      studies is nevertheless limited by its low specificity. The effect of age and
      educational level have been usually ignored when cut-off scores have been
      selected. The aim of this study was to evaluate the effect of age and educational
      level on the MMSE scores in a representative sample of subjects older than 70 and
      provide adjusted normalised data according to these two variables, after
      excluding subjects with dementia or cognitive decline. Population-based, cross
      sectional and longitudinal study of a representative cohort of 1367 subjects
      older than 70. All subjects with suspected dementia or cognitive decline received
      a neurological evaluation where clinical and etiological diagnosis were
      established. Normal MMSE scores, as defined by the 10th percentile, varied
      significantly across age and educational level groups. Exclusion of demented or
      cognitively declined patients from the reference population reduced the
      variability and "range of normality", but this remained excessively high in the
      older and less educated groups. The use of different cut-off points for each age
      and educational level groups may improve the specificity and applicability of the
      MMSE in population-based epidemiological studies. However, the wide amplitude of
      the range of normality suggests that different approaches, other than this
      vibariate analysis, may prove more adequate in the selection of cut-off scores
      for the MMSE.

PMID- 9608218
TI  - [Analysis of prognostic factors in adults with chronic subdural hematoma].
AB  - The objective of the study is the analysis of prognostic factors observed in the
      evolution of 65 patients who presented chronic subdural hematoma surgically
      evacuated. Morbimortality ratio corresponding to our surgical technique is also
      presented. A retrospective statistical analysis of epidemiologic, clinic and
      radiologic factors was performed. Personal background of alcoholism or
      coagulopathy, decrease of the level of consciousness, a lower score at the
      Glasgow Coma Score, a maximum thickness of the hematoma superior to 2 cm, and the
      respiratory and neurologic complications were found to be related to a worst
      prognosis. Our surgical technique showed 4.6% of mortality and 1.5% of
      recurrence. Detection of prognostic factors may have important implications in
      the selection of patients for surgery. Our small craniectomy has similar clinical
      outcome than other surgical methods.

PMID- 9608220
TI  - [Genetic counseling in neurology: practical and ethical considerations].

PMID- 9608219
TI  - [Bilateral sympathetic reflex dystrophy related to phenobarbital].

PMID- 9608221
TI  - [Temporal mesial sclerosis syndrome in epilepsy].
AB  - Mesial temporal sclerosis is a frequent cause of epilepsy. Patients with mesial
      temporal sclerosis usually have an early brain insult, a febrile convulsion in
      most cases, and a seizure free interval of variable duration. This is followed by
      complex partial seizures with stereotypic semiology. Histological analysis of the
      hippocampal formation demonstrates a well defined pattern of cell loss and axonal
      proliferation. This pattern indicates selective cell vulnerability to the
      excitotoxic process that causes mesial temporal sclerosis, and synaptic and
      axonal reorganization, which are involved in the pathogenesis of this disorder.
      Epilepsy associated with mesial temporal sclerosis is not a static process,
      neurons in this region of the temporal lobe are physiologically and biochemically
      active, participating in the pathophysiology of the disease by facilitating the
      recurrence of seizures. There are no pathognomonic findings in mesial temporal
      sclerosis, but its confident diagnosis can be achieved by convergence of
      different lines of evidence, including clinical, morphological, and functional
      findings. Complex partial seizures are often resistant to antiepileptic
      medication, while surgical resection of the epileptic focus provides seizure
      freedom in a large number of patients.

PMID- 9608222
TI  - [Pourfour du Petit syndrome].
AB  - The Pourfour du Petit's syndrome is characterized by the unilateral appearance of
      mydriasis, lid retraction and exophthalmos. It suggests the existence of a
      localized oculosympathetic hyperactivity. It tends be to caused by injuries that
      suppose a stimulus of the sympathetics fibers at level of the proximal portion of
      the first dorsal root or in the cervical sympathetic chain. We report the
      clinical case of a young patient who developed a Pourfour du Petit's syndrome
      secondary to a small condrosarcoma of the proximal portion of the first rib. The
      observation of this syndrome is exceptional but its knowledge permits, by the
      great topographic value that possesses, a rapid identification of the causative
      injury.

PMID- 9608223
TI  - [SUNCT type headache. A report of a new case. Short-lasting, unilateral,
      neuralgiform, headache attacks with conjuctival injection and tearing].
AB  - We report a new case of short-lasting, unilateral, neuralgiform headache attacks
      with conjunctival injection and tearing (SUNCT). This rare headache, described in
      1978, shares clinical traits with trigeminal neuralgia and cluster headache and
      its diagnostic classification as a unilateral headache with autonomic involvement
      has been the subject of considerable debate. The etiology of SUNCT is unknown,
      although it is considered a highly difficult pain to treat. We discuss our
      patient's symptoms and response to treatment with carbamazepine.

PMID- 9608224
TI  - [Clinical pseudo-peripheral presentation of cerebral lesions].
AB  - Small size cerebral lesions, located strategically, can determine the presence of
      sensitive and motor signs limited to a part of an extremity, clinically
      suggesting peripheral nervous system affectation, determining erroneous
      diagnostic and therapeutic decisions. We present 5 patients initially diagnosed
      of peripheral nervous system pathology, which were finally diagnosed of cerebral
      lesions (2 lacunar infarcts, multiple sclerosis, progressive multifocal
      leucoencephalopaty, multicentric astrocytoma). In all, clinical examination
      disclosed incongruous distribution of the sensitive manifestations and myotatic
      reflexes were present. CT studies were normal in three patients whereas MRI
      showed lesions in all cases. Lesions were smaller than 1.5 cm in diameter
      (greater in the case of multicentric astrocytoma), and were subcortically located
      in the opposite cerebral hemisphere to the affected extremity. Sensitivomotor
      signs restricted to an extremity not concordant with a nervous or radicular
      distribution and with presentation of myotatic reflexes, make it necessary to
      look for a central nervous system lesion. Lesion will be located in the opposite
      cerebral hemisphere and MRI will be the elective complementary exam.

PMID- 9608225
TI  - [Myoclonus induced by prednimustine].

PMID- 9608226
TI  - [Mandibular VII cranial nerve paralysis due to endarterectomy].

PMID- 9608227
TI  - [Charles Bonnet syndrome: a case report].

PMID- 9608228
TI  - [Tick-borne encephalitis--etiopathogenesis and implications for public health in
      Poland].
AB  - Tick-borne encephalitis (tbe) belongs to infectious units being under study in
      Poland since over 40 years: clinical, virological, immunological, epidemiological
      (see eg. fig. 1 of the review) observations succeeded in developing tbe map of
      Poland, and organization of satisfactory diagnostic virological control of the
      disease. This article covers most important data since the early (1952-1953)
      expeditions to the endemic districts of Poland, studies of human beings, animal
      reservoir, both wild and domestic animals, biological vectors, migrating and
      local birds, frequency of virus isolations from man, ticks, mosquitos, wild
      rodents, with special reference to specific (vaccines, immunoglobulins)
      prophylaxis and associated unexpected and negative reactions. The article points
      also on north-east districts as of high tbe exposure, on described milk
      associated outbreaks. The problems are discussed in relation with analogical
      and/or probable reactions related with other viral infections. Because of so
      meritorically differentiated and long-time performed studies and observations,
      the tbe is still in center of medical and public interest in Poland.

PMID- 9608229
TI  - [Diagnostic molecular microbiology--identification of Staphylococcus
      epidermidis].
AB  - The species Staphylococcus epidermidis is the predominant coagulase-negative
      staphylococci (CNS) isolated from clinical sources. S. epidermidis is now
      recognized as an important nosocomial pathogen. Identification of CNS is often
      performed using diagnostic kits based on biochemical or immunological reactions.
      However, these kits are often unreliable for the identification of CNS species
      including S. epidermidis. Currently, ribosomal RNA (rRNA) analyses are the most
      powerful methods for determining phylogenetic relationships among microorganisms
      and also for identification of species. Several aspects of construction of
      ribosomal probes for identification of CNS species are presented and discussed.
      Additionally, the application of restriction fragment length polymorphisms (RFLP)
      of rRNA genes for differentiation of clinical isolates of S. epidermidis is
      shown.

PMID- 9608230
TI  - [Genetic evaluation of tolerance to alcohol].
AB  - Alcohol sensitivity which is genetically controlled changes the risk of alcoholic
      diseases development in such individuals. There are differences in the allelic
      frequencies of the ALDH2, ADH2 and ADH3 loci, between alcoholics and
      nonalcoholics. It was shown that the atypical ALDH2/2 is an alcohol-rejecting
      gene and the usual ALDH1/2 gene is a major "alcoholic" gene. The kinetic
      differences of ADH2 isozymes may also affect drinking behavior. In conclusion,
      genetic polymorphism of the ALDH and ADH genes influence the risk of alcoholism
      development. It may be possible to control alcoholism by suppression of
      "alcoholic" genes expression through genomic intervention.

PMID- 9608231
TI  - [The effect of alcohol on the immune system and cytokines].
AB  - Chronic alcoholism is a disease, which is known to affect individual's resistance
      to infections. Alcohol has a variety of short- and long-term effects on cell
      mediated and humoral immune response. Alcohol also affects the production, site
      of action and metabolism of cytokines, which are regulatory peptides of the
      immune and inflammatory response of lymphocytes, monocytes/macrophages and a
      variety of other cell types. In this review, current knowledge regarding the
      effect of alcohol on the immune system and the release and action of cytokines in
      humans and in animal models, in vivo and in vitro, is presenting. Furthermore,
      the role of cytokines in development of alcoholic liver disease is also
      discussed.

PMID- 9608232
TI  - [Cytotoxic mechanism and antineoplastic action of etoposide].
AB  - Etoposide differs from its parent podophyllotoxin--classical spindle poison;
      unlike this compound etoposide delays progression of the cell cycle through the
      late S or early G2 phase. Etoposide inhibits uptake and incorporation of
      nucleosides into tumour cells but at the concentrations higher than those which
      are cytotoxic. Single- and double-strand breaks caused by etoposide in cellular
      DNA are generally considered as the initial event which leads to cell death; the
      DNA strand breaks result from stabilization of the cleavable complex of
      topoisomerase II DNA with DNA by etoposide. On the other hand metabolites of
      etoposide are also likely to exert cytotoxic action. Finally, etoposide has been
      shown to induce apoptosis, active, energy-dependent process of cellular self
      destruction, in human tumour cells.

PMID- 9608233
TI  - [Phosphoribosyltransferase (APRT) deficiency--molecular and clinical aspects of
      dihydroxyadeninuria].
AB  - The lack of purine salvage enzyme, adenine phosphoribosyltransferase (APRT), is a
      rare genetic defect that leads to excessive excretion of 2,8-dihydroxyadenine in
      urine. Due to its low solubility and nephrotoxicity, the defect may result in
      urolithiasis and renal failure. This review article describes genetic,
      biochemical and biophysical basis of the disease called dihydroxyadeninuria, as
      well as clinical problems of diagnosis and treatment.

PMID- 9608234
TI  - [Toxoplasmic and chagasic meningoencephalitis in patients with human
      immunodeficiency virus infection: anatomopathologic and tomographic differential
      diagnosis].
AB  - Twenty-two HIV+ patients with encephalitis were studied. Of these, 7 had
      meningoencephalitis due to Toxoplasma gondii (MT) and 15 due to Trypanosoma cruzi
      (MC). Pathologic and computerized axial tomography (CAT) changes were compared.
      We found that focal necrotizing encephalitis due to Toxoplasma involved the
      cerebral cortex and the basal ganglia, whereas lesions due to Trypanosoma cruzi
      were centered in the white matter, sometimes extending into the cortex.
      Hemorrhages, myelin lesions and organisms were more pronounced in chagasic than
      in toxoplasmic encephalitis. These findings are consistent with the literature
      reviewed.

PMID- 9608235
TI  - [Listeria monocytogenes meningitis. Case reports in patients from the Federal
      District].
AB  - It has been shown the role of Listeria monocytogenes as a etiological agent
      identified by bacteriological analysis among cases of human meningitis in
      Distrito Federal, Brazil. Laboratorial characteristics and some clinical and
      epidemiological aspects are reported.

PMID- 9608236
TI  - [Renal function aspects in carriers of the human immunodeficiency virus].
AB  - The occurrence of alterations was verified in some parameters of the asymptomatic
      individuals' renal function infected by the virus of the human immunodeficiency
      (HIV). Forty seven individuals were studied, taking place renal functional tests,
      as: creatinine clearance, clearance of free water, clearance osmolar,
      reabsorption tubular proximal and distal of sodium and potassium and urinary pH.
      The results revealed significant differences (p < 0.05) in the urinary pH, larger
      in the group with HIV (6.36 +/- 0.41), that in the controls (6.02 +/- 0.41); in
      the clearance of free water, that indicated reabsorption of larger water in the
      group with HIV (1.00 +/- 0.64 ml/min) and in the clearance osmolar, that was 2.00
      +/- 0.83 ml/min in the group with HIV and 1.57 +/- 0.48 ml/min. The remaining of
      the indicators of renal function was not shown statistically different between an
      and other group. It was ended that those differences are significant, in spite of
      the absolute values they be inside of the normality, because could be associated
      to late evolutionary alterations of the disease, such as the increase of the
      frequency of infections of the urinary treatment and the dilution hyponatremia.
      More studies are necessary for if they confirm those hypotheses.

PMID- 9608237
TI  - [Vibriocidal and agglutinating antibodies in the urban population in the
      municipality of Manacapuru/AM (1992-1993)].
AB  - A serological study was carried out involving 1,196 individuals residents in the
      urban area of Manacapuru--Amazonas, to evaluate the behavior of vibriocidal and
      agglutinating antibodies. A systematic random sampling procedure was employed to
      obtain the sample. A year later a 2nd sample of serum was obtained from 120
      individuals selected among the participants of the survey. Vibriocidal antibodies
      microtitulation and seroagglutination in tubes were employed. The correspondence
      between the studied antibodies was determined by the correlation coefficient
      calculated according to the frequency of the titles detected. The analysis of the
      results revealed positive correlation between the antibodies (r = 1.0) and a
      decrease in titles in a large proportion of the positive samples one year later.

PMID- 9608238
TI  - Detection of HTLV-IIa blood donors in an urban area of the Amazon Region of
      Brazil (Belem, PA).
AB  - The human lymphotropic viruses type I (HTLV-I) and type II (HTLV-II) are members
      of a group of mammalian retroviruses with similar biological properties, and
      blood transfusion is an important route of transmission. HTLV-I is endemic in a
      number of different geographical areas and is associated with several clinical
      disorders. HTLV-II is endemic in several Indian groups of the Americas and
      intravenous drug abusers in North and South America, Europe and Southeast Asia.
      During the year of 1995, all blood donors tested positive to HTLV-I/II in the
      State Blood Bank (HEMOPA), were directed to a physician and to the Virus
      Laboratory at the Universidade Federal do Para for counselling and laboratory
      diagnosis confirmation. Thirty-five sera were tested by an enzyme immune assay,
      and a Western blot that discriminates HTLV-I and HTLV-II infection. Two HTLV-II
      positive samples were submitted to PCR analysis of pX and env genomic region, and
      confirmed to be of subtype IIa. This is the first detection in Belem of the
      presence of HTLV-IIa infection among blood donors. This result emphasizes that
      HTLV-II is also present in urban areas of the Amazon region of Brazil and
      highlights the need to include screening tests that are capable to detect
      antibodies for both types of HTLV.

PMID- 9608239
TI  - [Clinical cross-sectional and epidemiologic study of Chagas disease in a rural
      area of the Argentinian northeast].
AB  - The main goal was to know the epidemiologic, clinical, electrocardiographic and
      radiologic characteristics among a population of seropositives and seronegatives
      to Trypanosoma cruzi in a rural area of the Department of San Miguel, province of
      Corrientes, Argentina. One hundred and thirty-two patients of different ages: 2
      79 years old were researched (58 males, 74 females). In order to make a thorough
      assessment clinical evaluation and cardiologic testing were carried out. Signs
      and symptoms consistent with heart disease, blood pressure, 12-lead ECG registry
      and chest x-ray (PA view) were registered. In signs and symptoms, abnormal ECG
      patterns and radiologic abnormalities, non-significant statistic difference were
      observed. Although we were unable to find a significant relationship between
      chagasic infection and a higher prevalence for heart disease, it is important to
      stress the fact that 54.0% of the studied population was largely composed of very
      young patients whose ages were less than 20 years old, and 45.0% of those older
      than 41 years showed ECG abnormalities.

PMID- 9608240
TI  - [Review of the biologic and diagnostic aspects of Trypanosoma (Herpetosoma)
      rangeli].
AB  - This review has three objectives: a) To stimulate further research of this
      prevalent human infection b) to examine the progress of current diagnostic
      techniques and c) to emphasise the significance of the flagellate parasite
      Trypanosoma (Herpetosoma) rangeli in Chagas' Disease endemic areas of South and
      Central America. Both Trypanosoma rangeli and Trypanosoma cruzi overlap in many
      of the areas of Latin America utilising the same triatomine vectors. Also a vast
      range of mammalian species have been found naturally infected with T. rangeli.
      The biology of the parasitism of T. rangeli is revised and emphasis is given
      regarding its biological cycle. T. cruzi and T. rangeli share common antigens and
      cross react serologically. Human infection in the chronic phase may be
      misdiagnosed as T. cruzi infection. Conventional and modern diagnostic and
      identification methods are discussed. Unfortunately we do not know the real
      distribution of T. rangeli infections in most areas and epidemiological studies
      to examine concomitant dual infections deserve further investigation.

PMID- 9608241
TI  - [A case of mucocutaneous leishmaniasis treated with success with a low dose of
      pentavalent antimonial].
AB  - The authors report a case of a 89 years-old woman with mucocutaneous
      leishmaniasis and previous diabetes mellitus and high blood pressure, who had
      been treated with allopurinol for 10 months without healing of lesions.
      Afterwards, she has been treated with meglumine antimonate, "glucantime" for 4
      days, with a total dose 2,380 mg of Sbv, but developed cardiac side effects and
      hypokalemia, hence the treatment was withdrawn. However, this patient developed
      total clinical regression of lesions, in spite of she has been received low dose
      of this drug.

PMID- 9608242
TI  - [Histoplasmosis in the region of the hard palate simulating a lesion caused by
      Leishmania].
AB  - A case of histoplasmosis at the oral cavity simulating mucocutaneous
      leishmaniasis is reported. The initial suspicion of leishmaniasis was not
      confirmed due to lack of amastigotes and no reactivity of the Montenegro's skin
      test. Diagnosis of histoplasmosis was done by Grocott's stained smears and
      isolation of Histoplasma capsulatum in Sabouraud's-agar slants. Treatment with
      Amphoterecin B led to complete remission of the lesion.

PMID- 9608243
TI  - [An attempt to detect Trypanosoma cruzi in the peripheral blood of patients with
      Chagas' disease, in chronic phase, using quantitative buffy coat (QBC)].
AB  - Taking for granted the sensitivity of the Quantitative Buffy Coat (QBC) system,
      as documented in a murine experimental model, we assayed to detect Trypanosoma
      cruzi in the peripheral blood of 100 patients with Chagas disease in its chronic
      phase. By means of the method, no positivity occurred, evently as a consequence
      of small parasitemias, undetectable by this technique as assessed by the cases in
      consideration.

PMID- 9608244
TI  - [Rational radiologic diagnosis of breast carcinoma].
AB  - For a favourable prognosis breast cancer must be diagnosed as early as possible.
      Among available imaging modalities (mammography, sonography, DAS, thermography,
      CT, MR) only mammography has been shown to produce a significant reduction in
      mortality, but unfortunately only for women above 50 years of age. The technical
      requirements, and the standard techniques and the appearance of benign and
      malignant breast tissues are described. The routine use of ultrasound in the
      evaluation of palpable masses remains controversial. Ultrasound technology is
      incapable of detecting early-stage cancers reliably. By "using dynamic MRM",
      i.e., repetitive imaging of the same slice before and at short time intervals
      after the injection of a contrast medium, high sensitivity and specificity is
      achieved in detecting breast cancer of different histologies. MR-mammography
      should be used in all cases where there is a discrepancy among radiographic,
      sonographic or clinical findings.

PMID- 9608245
TI  - [Relative indicators for disease outcome in breast carcinoma].
AB  - Tumor size, axillary nodal status, histologic grading and the hormonal receptor
      status are the established prognostic factors for breast carcinoma. Concurrent to
      these factors the clinical validation of the new innovative tumor characteristics
      from molecular biology is difficult to achieve. Clinicians are more and more
      interested in indicators of response to particular treatments (predictive
      factors) and less in prognostic factors relevant for the natural course. The
      hormonal receptor status is the best known predictive factor with regard to the
      response to hormonal treatment. Among the innovative parameters the tumor
      suppressor gene p53 and the oncogene Her2/neu show a good correlation to
      sensitivity to cytostatic treatment. The detection of more and more molecular
      mechanisms of tumor growth and tumor spread raise hopes that innovative treatment
      approaches will lead to an antineoplastic effect. The molecular tumor parameters
      then may play the role of predictive factors for a specific treatment. For the
      present the established tumor factors should be used as the base for a treatment
      plan and the available already known predictive factors should be taken into
      consideration.

PMID- 9608246
TI  - [Tumor risk consultation for predisposed women from high risk cancer families].
AB  - Germline mutations of the cancer susceptibility genes BRCA1 and BRCA2 seem to
      lead to a very high risk for breast and/or ovarian cancer. Therefore, genetic
      counselling and identification of high-risk families may be essential to offer
      the opportunity to participate in a specific early cancer detection program and
      to provide individualized psychological support. In a two year period (August
      1994-August 1997) 304 consultees present for genetic counselling at the
      interdisciplinary cancer genetic clinic (Department of Obstetrics & Gynecology
      and Human Genetics, Heinrich-Heine-Universitat, Dusseldorf). For genetic testing
      a BRCA1/2 mutation detection strategy including protein truncation test (PTT),
      single strand conformation polymorphism (SSCP), and direct DNA sequencing is
      used. 161 families fulfilled the inclusion criteria; at present, 72 families for
      whom complete analytical material is available are analyzed. Although genetic
      testing for BRCA1 and BRCA2 is technically challenging, women with a family
      history of multiple sporadic breast/ovarian cancers and those with a hereditary
      BRCA1 and BRCA2 gene defect may be distinguished. For the first group of
      consultees this may ease their concern, for the second group preventive measures
      including an early cancer detection or prevention program, psychological support
      or prophylactic surgery may be discussed.

PMID- 9608247
TI  - [Surgical therapy strategies in carcinoma in situ of the breast].
AB  - The surgical treatment of carcinoma in situ of the breast depends on the
      histological type. After detecting a lobular carcinoma in situ (CLIS) either an
      intensive (aftercare) follow-up is recommended or a bilateral mastectomy. The
      choice for one of these two very different forms of therapy can be done only
      after intensive psychological dialog with patient. The reason for the different
      forms of further treatment is the multicentric and often bilateral occurrence of
      CLIS and the potential risk of developing an invasive cancer. The therapy of the
      ductal carcinoma in situ (DCIS), which often spread out in a segment of one
      breast, is the total excision of the lesion with clear margins. The Van Nuys
      Prognostic Index depending on the histological results (tumor-diameter, thickness
      of clear margins, pathocytologic classification) indicates further treatment such
      as radiotherapy or mastectomy to lower the chance of local recurrence.

PMID- 9608248
TI  - [Radiotherapy of in situ carcinoma of the breast. EORTC Breast Group].
AB  - More and more breast cancers are being detected at an situ stage. Carcinoma in
      situ (CIS) can be divided in two categories, depending on where it arises. Ductal
      CIS arises in the ducts. Malignant epithelial cells are found within the ducts
      but there is no invasion through the basement membrane. Large tumors tend to be
      multicentric along the ducts resulting in underestimation of the treatment volume
      for tumorectomy and radiotherapy. Lobular CIS occurs in the lobules and may
      extend into the ducts in the same way that ductal CIS may extend into the
      lobules, resulting in occasional difficulty in distinguishing between the two.
      Preinvasive ductal carcinoma or DCIS is being diagnosed more often and now
      constitutes 22% of breast cancers detected by mammography. Many of these lesions
      are nonpalpable. Standard therapy has been total mastectomy. Breast conserving
      operations such as lumpectomy alone will yield a high recurrence rate of 20% and
      half of this will reappear as invasive cancer. DCIS is not proven to be
      radioresistant. The optimal dose for radiotherapy of DCIS is unknown. Recent
      results from an NSABP trial B17 of lumpectomy with and without radiotherapy
      suggested that lumpectomy with postoperative radiation therapy gave acceptable
      relapse free survival of 83% compared to 72% after surgery alone (p = 0.00004)
      and low recurrence rates of 1.9% vs 4.8%. The results of the corresponding EORTC
      studies will be published in 1998.

PMID- 9608249
TI  - [Diagnosis and therapy of breast carcinoma--an interdisciplinary challenge].
AB  - Screening studies in patients older than 50 years show a reduction of mortality
      and an increase of early stages. Newly diagnosed breast cancer confronts the
      patient and the clinician with multiple treatment decisions. Breast conserving
      surgery has become standard therapy for early breast cancer. Key elements in the
      selection of patients for treatment with local or transferred tissue or
      mastectomy include preoperative mammography, careful pathologic evaluation of the
      needle or core biopsy specimen, and an assessment of the patients desires in
      order to balance the risk of local recurrence against preservation of a
      cosmetically acceptable breast. MR-mammography and sonography complement
      mammography to define the extent of the disease preoperatively. This review
      examines some of the local treatment options, the choice between breast
      conserving treatment and mastectomy, how best to treat the axilla, the optimal
      sequencing of local and systemic therapy. Breast conserving therapy with
      radiation has been recognized as a standard strategy, because of the low
      incidence of local failure and minimal postoperative deformity compared with that
      of quadrantectomy without radiation. High-dose chemotherapy is being evaluated in
      the treatment of metastatic and high-risk primary breast cancer.

PMID- 9608250
TI  - [Therapeutic strategy in advanced breast carcinoma].
AB  - Breast cancer metastastic to sites beyond regional axillary lymph nodes
      represents a historically incurable condition despite the judicious use of
      various hormonal manipulations and surgical and radiotherapeutic interventions,
      and the application of active cytotoxic chemotherapeutic agents for hormone
      refractory disease. The systemic management of patients with hormone refractory
      breast cancer is classically characterized by the thoughtful, stepwise
      administration of cytotoxic chemotherapeutic agents. At various junctures in the
      continuum of care, a patient/physician analysis of the potential risks and
      benefits of chemotherapy may lead to the decision to proceed with subsequent
      systemic therapy, to consider an investigational strategy like new active agents
      or high dose therapy, or to opt for supportive care alone.

PMID- 9608251
TI  - [The 40th anniversary of the journal Sudebno-meditsinskaia ekspertiza].

PMID- 9608252
TI  - [The scientific activities of the Department of Forensic Medicine of the Moscow
      Medical Stomatology Institute on the pages of the journal Sudebno-meditsinskaia
      ekspertiza].

PMID- 9608253
TI  - [The contribution of military forensic physicians to forensic medical science].

PMID- 9608254
TI  - [Medical law in the activities of the forensic medical service of Russia].

PMID- 9608255
TI  - [The use of a modelling method in craniometry].
AB  - Laser interferometry is proposed for accurate measurements of the external
      parameters and fixation of the relief of human skull surface. This method creates
      a detailed three-dimensional computer model of the object of investigation, which
      can be used in automated systems of personality identification based on
      investigation of the skull and life-time photos. Further development of the
      method opens new vistas in automation of the trassological and ballistic
      identification.

PMID- 9608256
TI  - [The morphological changes in the internal organs in hemochromatosis].
AB  - Visceral changes were studied by histological and electron-microscopic methods in
      cadavers of 18 subjects dead from hemochromatosis. Pronounced visceral changes in
      all cases represented a characteristic tetrad of signs: bronze-colored skin,
      pigmentary cirrhosis of the liver, involvement of the pancreas, and
      cardiomyopathy. In forensic medical practice hemochromatosis can be found in
      subjects who were probably genetically predisposed to it and, as a rule, had a
      history of alcohol abuse. Among the numerous complications of the disease, the
      most incident are cardiac pathology (dilatation cardiomyopathy) and diabetes
      mellitus with concomitant intoxications caused by various inflammations.

PMID- 9608257
TI  - [Anomalies of the thyroid cartilage and their forensic medical significance].
AB  - A total of 433 completely prepared cadaveric neck organ complexes were examined.
      Four variants of the thyroid cartilage structure were distinguished, with due
      consideration for the mobility of its attachment to the hyoid bone; three of
      these variants included abnormal cases. Abnormalities were revealed in 4.8% of
      cases, and were almost two times more incident in men than in women. The shape of
      the thyroid-hyoid junction notably influences the vulnerability of the neck
      structures. Vulnerability of the thyroid cartilage and hyoid bone differed much
      even among the normal variants. Abnormal or even normal thyroid-hyoid junction
      can be taken for a fracture by palpation; therefore, thorough complete
      preparation under laboratory conditions is obligatory.

PMID- 9608258
TI  - [The use of the Regulations for the Forensic Medical Expertise of the Severity of
      Harm to Health in expert practice].

PMID- 9608259
TI  - [Difficulties in the forensic medical expertise of mild craniocerebral trauma].
AB  - The authors discuss objective medical labor and forensic medical expert valuation
      of the severity of corporal injuries and performance abilities of subjects in
      various periods after slight concussion or confusion of the brain. Files of a
      neurotraumatology department over 11 years (10072 case histories) and 3769
      conclusions, made by the Regional Bureau of Forensic Medical Expert Evaluation on
      the health status of subjects exposed to slight concussion and(or) confusion of
      the brain, are analyzed. The incidence of craniocerebral injuries has increased,
      mainly at the expense of grave and medium-severe injuries. The authors detected
      faults in the examination and description of the mechanism of injury and
      neurological status and its changes, which impede expert evaluation. They
      emphasize the need in a universal scientifically-based approach to this problem,
      which is to be solved by united efforts of medical, legal, and social workers.

PMID- 9608260
TI  - [An expert evaluation of molecular genetic individualizing systems based on the
      HUMvWFII and D6S366 tetranucleotide tandem repeats].
AB  - Amplification systems based on highly polymorphic tetranucleotide microsatellites
      from the family of von Willebrand factor gene (vWF) and locus D6S366 repeats are
      developed at the State Research Center Gos-NII Genetika. A complex expert
      evaluation of two such molecular genetic individualizing systems based on loci
      HUMvWFII and D6S366 is performed in order to investigate their probable use in
      forensic medical personality identification.

PMID- 9608261
TI  - [The characteristics of the enzymatic amplification of locus D17S5 alleles: the
      need to assess the stability of the amplification profile].
AB  - Amplification behavior of one chromosome locus (D17S5), widely used in
      identification studies, is investigated. The effect of preferable amplification
      of alleles, characteristic of this locus, often leads to an erroneous conclusion
      about homozygosity. Our studies showed, that along with the hazard of typing
      false homozygotes in analysis of locus D17S5, more intricate cases with genotype
      distortion can occur in expert practice, which may be characterized not only by
      partial loss of the true alleles, but even by amplification of nonspecific
      (nonallele) fragments simulating the false-heterozygotic allele profile. Analysis
      of the stability of amplification profile helps solve this problem.

PMID- 9608262
TI  - [The use of proteases for enhancing the sensitivity of detecting ABO system
      antigens by an absorption-elution reaction in blood stains].
AB  - The sensitivity of the absorption-elution test (AET) for the detection of A, B,
      and H antigens in blood traces can be appreciably increased by using
      serologically active proteases at different stages of the test. A sensitive AET
      modification is developed, detecting group antigens in far lesser amounts of the
      material than by routine AET without proteases. A higher sensitivity of the
      antigen-antibody reaction between enzyme-treated erythrocytes and tested blood
      traces permits the use of standard group-specific sera less active than usually;
      the actually solves the problem of deficit of the sera fit for this test.

PMID- 9608263
TI  - [The expediency of studying the contents under the nails].

PMID- 9608264
TI  - [The applied aspects of telecommunication in medicine].

PMID- 9608265
TI  - [The cause and nature of the death of the Tsarevich Dimitrii].

PMID- 9608267
TI  - [State Virology and Biotechnology Research Center "Vector"].

PMID- 9608266
TI  - [The oldest forensic medical morgue in Moscow (on the 150th anniversary of the
      Lefortovo Morgue)].

PMID- 9608268
TI  - [Chimeric hepatitis B core antigen particles as a presentation system of foreign
      protein epitopes].
AB  - The paper presents data available in the literature and the author's own
      experimental findings as to the construction of chimeric hepatitis B core antigen
      (HBcAg) particles. The problems associated with the design of hybrid HBcAg
      particles and the ways of solving arising problems are considered. Data from
      studies of the antigen and immunogenic properties of hybrid HBcAg particles.

PMID- 9608269
TI  - [Monoclonal antibodies in human hepatitis A virus immunoenzyme diagnosis].
AB  - Antigen and antibody detection in EIA is a good tool in diagnosing HAV
      infections, especially in their differentiation from other hepatitides.
      Commercial kits containing polyclonal antibodies and murine MAbs to identify HAV
      are now available. Rat MAbs have not been assayed so far. Peroxidase-labelled rat
      MAbs and purified rat MAbs as antigen capture were used to modify commercial
      "VectoHep A-IgM" and "VectorHep A-Ag" kits. The results obtained with modified
      "VectoHep A-IgM" and "VectorHep A-Ag" kits with labelled rat MAbs suggest that
      labelled rat MAbs can increase the sensitivity and specificity of EIA. MAbs used
      as antigen capture and labelled antibodies permit at least an 8-fold increase in
      sensitivity as compared to polyclonal antibodies. The modified "VectorHep A-Ag"
      kit with labelled rat MAbs provided 100% sensitivity and specificity in EIA. The
      modified "VectorHep A-Ag" kit also allowed the authors to determine viral
      antigens in the cell lysate, homogenates of the infected monkey liver, stools
      from patients, and sewage water samples. The rat MAbs modified kits can be
      recommended for using in epidemiological and clinical studies of HAV infections.

PMID- 9608270
TI  - [Detection of unintegrated forms of proviral DNA in HIV infections].
AB  - The content of 1-LTR and 2-LTR circular forms of HIV-1 proviral DNA was
      determined by nested PCR. Outer and inner primers for the first and second stages
      of PCR were selected in the env and gag regions that allowed the authors to
      simultaneously test 1- and 2 LTR of DNA HIV-1 forms in the analyzed samples. The
      accumulation of circular species of HIV-1 DNA was shown to occur during HIV
      infection as well for acutely infected cell lines as chronically infected
      mononuclear cells. The cell cultures providing productive infection was
      characterized by higher levels of 2-LTR circular HIV-1 DNA. Analysing the
      clinical samples demonstrated greater differences in the accumulation of the
      circular forms of proviral DNA. It was detected in 16 tested clinical samples
      both of 1-LTR and 2-LTR circular DNA in 6 samples and 1-LTR in 11 samples of 2
      LTR of HIV-1 DNA is a minor fraction in most clinical samples, but in some
      samples the relative content of 1-LTR/2-LTR DNA was shown to be 1:1.

PMID- 9608271
TI  - [Molecular genetic aspects of interferon induction and antiviral action].
AB  - Interferons (IFN) are cytokines with a wide range of biological activities. The
      most important function of IFN is associated with the induction of host
      resistance to viral infections. This paper discusses the well-known experimental
      data and the results of the authors' theoretical studies of the regularities of
      type 1 interferon induction and its antiviral action. The mechanisms both of
      interferon gene expression and transcription regulation of IFN-stimulated genes
      by IFNs and viruses are analyzed. The molecular mechanisms of IFN-induced
      resistance and the well-known strategies acquired by viruses to overcome IFN
      action are discussed. The authors' analyze possible regulation by IFN of its own
      expression and the role of IFN- and virus-induced expression of genes of
      antiviral response in the development of resistance to infection.

PMID- 9608272
TI  - [Molecular factors of orthopoxvirus virulence].
AB  - Orthopoxviruses encode numerous virulence factors. Viral inhibitors of apoptosis
      of infected cells have been revealed in recent years. Viral inhibitors of the
      host's non-specific inflammatory reactions are shown to play an important role in
      effectively propagating the virus. A number of inhibitors of antiviral interferon
      action cause a high interferon resistance of orthopoxviruses. Some modulators of
      immune response of the infected body encoded by orthopoxviruses have been
      discovered in the past years. Viral growth factor, some proteins of the envelope
      of extracellular virions, etc. are shown to be important for viral dissemination
      in the host. A general scheme of synthesis of molecular factors of orthopoxviral
      virulence is discussed.

PMID- 9608273
TI  - [Elaboration of live measles vaccine technology on human embryo lung diploid cell
      culture L-68].
AB  - Measles predominates among childhood droplet infections in many countries.
      Immunization of all human beings sensitive to this infection is the only radical
      measure in controlling measles. The quality of a vaccine is primarily determined
      by the properties of the virus strains and cell cultures and technology of
      production. Now live measles vaccine is produced in or country on the basis of
      fibroblasts from Japanese quail embryo. The production of live measles vaccine in
      the primary cell cultures has a number of drawbacks caused by the nonstandard
      pattern of the substrate and the probability of contamination. The use the
      certified human diploid cells deposited in liquid nitrogen in sufficient
      quantities is promising. The authors have elaborated a new technology of live
      measles vaccine production by using the Leningrad-16 virus strain on the basis of
      attested L-68 diploid cell culture from the human fetal lung. Experimental
      batches of vaccine were obtained and attested in accordance with the present
      requirements for immunobiological products.

PMID- 9608274
TI  - [Prospects of use human fetal fibroblasts in the treatment of various etiology
      wounds].
AB  - The investigations have demonstrated a high efficiency of the certified human
      fetal lung fibroblasts in the treatment of skin wounds of various etiology. For
      treatment, a fibroblast monolayer grown on a backing was applied to various types
      of wounds (burns frostbites, donor site suppurations) and in shin phlegmon. There
      was wound debrediment and rapid skin recovery. Employing the cells from the
      certified cell culture banks provides not only a biologically and genetic uniform
      material, but also makes it possible to standardize treatments which are useful
      for wide medical application, by delivering the standard cells to medical
      institutions which have no experience in culturing. To set up banks of cell
      cultures and to store them for a long time at a temperature of liquid nitrogen in
      adequate quantities of ampoules allow the cultured fibroblasts to be provided
      with if a large quantity of cells is required, which may be useful in
      emergencies.

PMID- 9608275
TI  - [Effects of tumor necrosis factor antiserum of the course of Marburg hemorrhagic
      fever].
AB  - The paper provides data on the effect of tumor necrosis factor (TNF) antiserum on
      the course of experimental Marburg hemorrhagic fever. On day 3 of the challenge
      of guinea pigs with the Popp strain of Marburg virus, the infection event was
      confirmed by PCR. On days 4-7, the infected animals intramuscularly received a
      TNF-alpha antiserum. The treated animals showed a 50% survival while all control
      animals died. It may be assumed that a course of death due to Marburg hemorrhagic
      fever in shocks brought about by inflammatory cytokines. Therefore, attempts may
      be made to treat this infection by using the drugs that are TNF antagonists.

PMID- 9608276
TI  - [Enhancement of epidermal regeneration by recombinant vaccinia virus growth
      factor].
AB  - Examining the specific activity has showed that recombinant vaccinia virus growth
      factor binds to appropriate receptors on the A-431 cell surface and prompts the
      healing acceleration of degree III burns in rats. This recombinant factor did not
      demonstrate pyrogenicity or toxicogenicity in tests on rabbits, guinea-pits,
      noninbred albino mice.

PMID- 9608277
TI  - [New method for diagnosis of lipid metabolic disturbances].
AB  - A new analytical procedure for determining the fraction composition (FC) of
      lipoproteins (LP) is developed on the basis of the physical method small-angle X
      ray scattering (SAXS). This method quantitatively determines the levels of the
      basic fractions of LP and their subfractions in plasma or serum to analyze LP FC
      and to diagnose lipid metabolic disturbances. The results obtained by this
      procedure were compared with those of gel-electrophoresis, biochemistry, and
      medical diagnosis. There was a good agreement of SAXS and routine methods. The
      new procedure shows extremely rapid (1.0-1.5 hr) analysis, uses a single reagent
      (such as the saccharose type), has a high accuracy, and resolution. The analysis
      requires as high as 0.05 ml of plasma or serum. LP FC may be analyzed both in
      protein-free and whole native plasma and sera. The findings may be used in
      clinical care for diagnosis of dyslipidemias and for researches.

PMID- 9608278
TI  - [Development of sera reference panels for quality control of ELISA diagnostic
      kits in Russia].
AB  - In the past 5 years, the investigators of the "VECTOR" SRB VB and the L.A.
      Tarasevich State Institute of Standardization and Control of Medical Biological
      Preparations have jointly designed sera reference panels containing anti-HIV-1
      IgG, anti-HCV IgG, and anti-HAV IgM which have been approved as national standard
      panels. The panels are intended for use in controlling the specificity and
      stability of the most widely used ELISA diagnostic kits and immunoblot test
      systems during production, control, and application stages. Some problems of
      development and production of these panels, including the representation of
      different sera in the panels and the selection of specific IgG concentrations in
      the different sera in the panel are described. The authors also attract attention
      to the stabilization of the specific characteristics of panel sera during storage
      and transportation.

PMID- 9608279
TI  - [Microscopic study of species specific features of hemostatic impairment in Ebola
      virus infected monkeys].
AB  - Pathological changes were studied in the blood vessels of baboons, green, rhesus,
      and cynomolgus monkeys at the end-stage Ebola (Zaire) infection. Marked
      microvascular lesions (capillary stasis, blood engorgement, thrombosis with blood
      cells, neutrophil accumulation, endothelial edema) were found in all the monkeys.
      These changes clearly indicate impaired organ blood supply. Multiple hemorrhages
      were formed by diapedesis without vascular wall destruction. Fibrin deposition
      and thrombi were features of hemostatic impairment in green and rhesus monkeys.
      Fibrin deposition and hemorrhages were not found in the cynomolgus monkeys. The
      possible mechanisms responsible for end-stage shock in Ebola virus-infection
      associated with microcirculatory disorders.

PMID- 9608280
TI  - Lessons from a monoclonal antibody to double-stranded DNA.
AB  - In this graduate school of Tokyo Medical and Dental University, I was given a
      somewhat vague but farsighted theme by a professor: "protein-DNA interaction."
      Within these simple words, I was given a free hand. Being curious about the
      etiology of connective tissue diseases, I began to study the biochemistry and
      pathophysiology of autoimmunity, especially the nature of anti-DNA antibodies
      that are the principal anti-nuclear antibodies observed in patients with systemic
      lupus erythematosus (SLE). My thesis was on the characterization of serum anti
      DNA antibodies purified by a novel method of affinity column chromatography.
      Thereafter, I remained involved in this fascinating field. In spite of the rapid
      progress in molecular immunology, the etiology of any particular systemic
      autoimmune disorder remains elusive at this point. Here, works on a monoclonal
      anti-DNA antibody performed in the laboratories of Dr. B. D. Stollar (Tufts
      University, Boston), Dr. Y. Kanai (University of Tokyo), and in our laboratory
      will be reviewed along with related articles.

PMID- 9608281
TI  - No significant role of Epstein-Barr virus in the tumorigenesis of Warthin tumor.
AB  - To determine the significance of Epstein-Barr virus (EBV) in the tumorigenesis of
      Warthin tumor, formaldehyde-fixed and paraffin-embedded specimens of 21 tumors
      from 18 patients were examined by polymerase chain reaction (PCR)-Southern
      hybridization, in situ hybridization (ISH), and immunohistochemistry. PCR
      Southern hybridization revealed the presence of EBV DNA in 13 of the 21 tumors
      (61.9%). However, ISH for EBV RNA showed that nuclei of the neoplastic epithelial
      cells of all tumors were negative. Although ISH for EBV DNA revealed that the
      nuclei of the neoplastic epithelial cells were positive in 4 of the 21 tumors
      (19.0%), the positive cells were sparsely distributed and there was no evidence
      of monoclonal proliferation of EBV positive neoplastic epithelial cells.
      Moreover, immunohistochemical reactions with antibodies against latent membrane
      protein 1 (LMP1) and EBV nuclear antigen 2 (EBNA2), were negative in all cases.
      Judging from these findings, we conclude that EBV does not play a major role in
      the tumorigenesis of Warthin tumor.

PMID- 9608282
TI  - Ectopic bone formation by biphasic calcium phosphate (BCP) combined with
      recombinant human bone morphogenetic protein-2 (rhBMP-2).
AB  - We investigated ectopic bone formation by biphasic calcium phosphate (BCP)
      combined with recombinant human bone morphogenetic protein-2 (rhBMP-2) in the rat
      dorsum. Under reduced pressure, rhBMP-2 was adsorbed onto BCP, which consisted of
      80% beta-tricalcium phosphate and 20% hydroxyapatite uniformly distributed in
      granules. Twenty Wistar rats were separated into 4 groups consisting of 5 animals
      each dosed with 2, 10, and 50 micrograms/700 microliters of rhBMP-2 and a control
      group (BCP only). Pieces of the BCP-BMP complex or only BCP were implanted under
      the dorsal skin of the rats. Histological sections were examined three weeks
      later. New bone was formed in all rats given 50 micrograms doses, but not in the
      2 micrograms and control groups. These results indicated that BCP combined with
      rhBMP-2 induced ectopic bone formation without additional carriers. Therefore,
      BCP granules alone can function as carriers for rhBMP-2 to induce bone formation.

PMID- 9608283
TI  - Repair of bone defect in primate mandible using a bone morphogenetic protein
      (BMP)-hydroxyapatite-collagen composite.
AB  - The purpose of this study was to evaluate a hydroxyapatite (HA)-collagen (Col)
      bone morphogenetic protein (BMP) composite as an osteoinductive bone substitute.
      Partially-purified BMP from bovine bone was mechanically mixed with highly
      purified type I collagen from calf dermis and then subsequently mixed with pure
      synthetic hydroxyapatite granules or block. The HA-Col-BMP composite, or the HA
      Col composite as a control, was implanted in a surgically-induced mandible bone
      defect (6 x 7 x 10 mm) in an adult Japanese monkey. The mandible was excised
      three months after implantation and studied histologically. The BMP-containing
      implant induced much more new bone than the control implant in all experimental
      animals of each group, with either HA granules or HA block. Newly formed bone was
      attached tightly to HA and infiltrated deeply into the pores of the HA of the BMP
      containing implant, while fibrous tissue existed between the host bone and HA in
      the control implant. Thus, we conclude that an HA-Col-BMP composite could be a
      superior biomaterial for a bone substitute.

PMID- 9608284
TI  - Proposals for state control of hi-tech devices.

PMID- 9608285
TI  - Local government to provide health care in W Cape.

PMID- 9608286
TI  - The ethics of physician-assisted suicide and euthanasia.

PMID- 9608288
TI  - Understanding the epidemic of HIV in South Africa. Analysis of the antenatal
      clinic survey data.
AB  - OBJECTIVES: To investigate the magnitude and the time course of the HIV epidemic
      in the provinces of South Africa from the antenatal clinic HIV surveys. DESIGN:
      We analysed the data on the provincial prevalences of HIV infection from 1990 to
      1996 using maximum likelihood methods to determine the intrinsic growth rate and
      probable asymptotic prevalence of HIV among women attending antenatal clinics.
      SUBJECTS: Women attending antenatal clinics and included in the national HIV
      prevalence surveys conducted by the Department of Health. RESULTS: 1. In KwaZulu
      Natal the epidemic is likely to peak at a prevalence of about 23% (95% confidence
      interval (CI) 19-36%). 2. The intrinsic doubling time does not differ
      significantly among the provinces. 3. The average length of the intrinsic
      doubling time is 12.0 months (95% CI 11.3-12.8 months). 4. The force of infection
      is approximately 1.00/year at age 16 years and declines at a rate of about 5% per
      year of age above 16 years. CONCLUSIONS: South Africa is likely to experience one
      of the worst HIV epidemics in Africa. The lack of statistically significant
      differences between the growth rates of the epidemic in the various provinces
      constrains the possible explanations that can be advanced to explain the time
      course of the epidemic and may in part be a consequence of migrancy. The
      intrinsic growth rate is higher than previous estimates and it is possible that
      in those provinces where the prevalence is still low it will eventually reach the
      same levels as in KwaZulu-Natal.

PMID- 9608290
TI  - The development of passive health surveillance by a sentinel network of family
      practitioners in South Africa.
AB  - OBJECTIVE: For the South African Sentinel Practitioner Research Network
      (SASPREN), a volunteer network of family practitioners in South Africa, to
      develop a health surveillance system through the surveillance of important health
      events. MOTIVATION: The incidence of important preventable diseases and the
      burden of disease are not reliably known in South Africa, both in the public and
      private sector. Incidence rates determined at primary care level could help with
      planning and delivery of appropriate health services and monitoring of the impact
      of intervention programmes. METHODS: Altogether 183 sentinel practitioners were
      recruited in nine provinces, from 2,478 doctors invited to participate. Of these
      120 were active in reporting all their new cases of 13 selected health events to
      the study centre on mailed postcards. After data-capturing, incidence rates were
      calculated for defined periods. Feedback was given to the sentinels through a
      newsletter and personalised reports. RESULTS: A network of sentinel family
      practitioners has been established in South Africa, and can provide incidence
      rates for both diseases and interventions through a simple and cheap surveillance
      system. The calculated rates demonstrated periodic trends for certain events, as
      well as inter-provincial, -gender and -population group differences. CONCLUSIONS:
      As the validity of the dataset and its generalisation to the whole population is
      uncertain, its usefulness as point estimates of incidence rates is unknown. This
      information serves as an important pointer for further research. The trends of
      these rates may provide a valuable tool for monitoring the impact of public
      health policies.

PMID- 9608289
TI  - Cost-effectiveness of ceftriaxone in the treatment of community-acquired
      pneumonia in adult hospital patients. A pharmaco-economic study based on a meta
      analysis.
AB  - OBJECTIVES: A retrospective analysis was conducted to assess the cost
      effectiveness of four intravenous antibiotic treatment regimens in the treatment
      of severe community-acquired pneumonia (CAP) in adults in a private hospital
      setting. The study compared some third-generation cephalosporin regimens with a
      second-generation cephalosporin and an amoxicillin/clavulanic acid (co-amoxiclav)
      regimen to investigate published South African treatment guidelines from a
      pharmaco-economic point of view. METHOD: A pharmaco-economic model of local
      costs, from a payer perspective, was based on the results of a meta-analysis of
      clinical papers from peer-reviewed journals. The study compared intravenous
      (i.v.) ceftriaxone (2 g once daily), cefotaxime (i.v. 2 g 3 times a day),
      cefuroxime (i.v. 750 mg 3 times a day, followed by 500 mg orally 3 times a day)
      and amoxicillin/clavulanic acid (1.2 g intravenously 3 times a day, followed by
      625 mg orally 3 times a day) [corrected]. RESULTS: An analysis of the odds ratios
      (ORs) of all two-way comparisons indicated that ceftriaxone ensured significantly
      higher probabilities of successful outcomes than the other antibiotic treatment
      regimens (ORs in the order of two were indicated). The pharmaco-economic results
      suggested that the ceftriaxone treatment regimen was the most cost-effective in
      the hospital treatment of CAP in adult patients. These results proved to be
      robust across sensitivity analyses for success rates and treatment days. A
      sensitivity analysis testing the assumption that patients could be discharged
      once the oral treatment was initiated indicated that the amoxicillin/clavulanic
      acid and cefuroxime treatment arms were more cost-effective. The clinical
      validity of such an assumption is questionable. CONCLUSION: Despite the
      conservative approach followed in terms of ceftriaxone data, both the clinical
      results and cost-effectiveness supported the use of ceftriaxone in the treatment
      of CAP in adults in the hospital setting.

PMID- 9608291
TI  - Generic substitution--comparing the clinical efficacy of a generic substitute for
      fluphenazine decanoate with the original product.
AB  - Long-acting neuroleptics have become the mainstay of the long-term treatment of
      schizophrenia, improving compliance and thus preventing relapse. Since
      schizophrenia is a common condition and treatment is usually long-term, this has
      important financial implications. OBJECTIVE: Generic substitution is an important
      cost-saving measure and generic psychopharmacological agents are also currently
      available in South Africa. There have been concerns about the quality of these
      products, but these often arise from anecdotal reports. This study was undertaken
      to compare the clinical efficacy of a generic substitute of fluphenazine
      decanoate with the original product. DESIGN AND SETTING: The study was a double
      blind randomised trial involving two parallel groups--generic substitution v.
      original product. Chronic schizophrenics, aged between 18 and 65 years, who had
      been on a constant dose of fluphenazine decanoate for at least 3 months preceding
      the trial, all treated as outpatients in the community, were studied. The
      Positive and Negative Syndrome Scale (PANSS) (positive scale) was used as
      measuring scale and patients were evaluated at inclusion and then every 2 weeks
      for the next 12 weeks. RESULTS: Both groups had a median change of zero in PANSS
      scores over the 12-week period. No clinically significant differences between the
      change in PANSS score were found in respect of the two products. CONCLUSIONS:
      Generic substitution could play an important role in containing the costs of
      health care in South Africa. Concerns about the quality and efficacy of these
      drugs should be investigated. In this study, no significant differences in the
      efficacy of the two products were found.

PMID- 9608292
TI  - An assessment of asthmatic patients at four Western Cape community pharmacies.
AB  - OBJECTIVES: To identify the profile of asthmatic patients visiting community
      pharmacies and to assess the appropriateness of their current asthma therapy.
      DESIGN: Patients were identified as either chronic, newly diagnosed or
      undiagnosed. Asthma status was assessed from their current symptom and medication
      profiles and from performance in an airways responsiveness test. Reversibility of
      > 15% was suggestive of probable airflow obstruction and such patients were
      referred to a medical practitioner. SETTING: Four community pharmacies located in
      different socio-economic areas, viz. Khayelitsha, Wynberg, Mitchell's Plain and
      Vrijzee, were selected. SUBJECTS: Participants over the age of 6 years, who
      suffered from recurrent cough, wheeze, chest tightness and/or breathlessness and
      used over-the-counter (OTC) and/or asthma medications, completed a questionnaire
      and participated in the airways responsiveness test. OUTCOME MEASURES: Effective
      control of asthma based on minimal symptoms, appropriate use of bronchodilator
      and anti-inflammatory therapies and absence of airflow obstruction. RESULTS: Of
      the 220 participants, 120 were identified as chronic, 7 as newly diagnosed and 93
      as undiagnosed. Chronic asthmatics suffered daily symptoms and used inadequate
      prophylactic anti-inflammatory therapy. Many undiagnosed asthmatics were unaware
      of their symptoms and took OTC medication indiscriminately. Based on peak
      expiratory flow rate measurements, > 50% of the screened patients displayed a
      reversibility of > 15%. CONCLUSIONS: Chronic and many undiagnosed asthmatic
      patients frequent community pharmacies for their medication. Such patients suffer
      recurrent asthma symptoms and use medication inappropriately, which results in
      suboptimal lung function. Pharmacists should play a more participatory role in
      the detection and management of asthma in the community.

PMID- 9608293
TI  - Risk factors for permanent hypernasality after adenoidectomy.
AB  - OBJECTIVES: To investigate the causes of persistent, apparently permanent
      hypernasal speech following adenoidectomy in 10 subjects without overt cleft
      palates, and to establish a protocol to be followed before this operation is
      performed. DESIGN: Retrospective and descriptive design. PARTICIPANTS: Ten
      subjects, fulfilling the following criteria, were included: (i) subjects had
      undergone adenoidectomy which resulted in hypernasal speech that persisted for
      longer than 3 months (and was therefore considered to be permanent); (ii)
      subjects did not have a cleft lip or overt cleft palate; (iii) there was no
      hearing loss of sufficient magnitude to account for the hypernasal speech; and
      (iv) the hypernasality was rated as severe by a speech therapist, could not be
      remedied by speech therapy alone and required further management by a plastic
      surgeon through pharyngosplasty. Ten subjects were found through the clinical
      records of speech therapists and plastic surgeons working in hospitals and
      private practice. The following information was obtained through interviews or by
      reading the case files: (i) identifying information; (ii) the presence of any of
      the factors reported in the literature to be associated with the permanent
      hypernasality or nasal emission, as well as the method of identification; and
      (iii) whether these factors had been identified before or after the
      adenoidectomy. RESULTS: Nine out of a total of 10 subjects showed preoperative
      perceptual and structural characteristics and/or case history factors that have
      been documented to constitute risk factors for the development of nasal speech,
      should an adenoidectomy be performed. The methods used to investigate these
      factors pre-operatively appear to have been inadequate. CONCLUSION: This
      undesirable sequel to surgery can be prevented if certain case history and speech
      factors are investigated and followed up with radiographic procedures if
      necessary.

PMID- 9608294
TI  - Disseminated histoplasmosis in an 'immunocompetent' child.
AB  - A rare case of severe disseminated histoplasmosis in a 7-year-old boy with
      apparently normal immune function is described. Current recommendations for
      diagnostic investigations, monitoring and the treatment of this disease with
      amphotericin B and itraconazole are reviewed.

PMID- 9608295
TI  - History of medicine. Medicine in Bloemfontein--anecdotes from the turn of the
      century.
AB  - During the first year of the 1899-1902 Anglo-Boer War many doctors and patients
      arrived in Bloemfontein. One of these, Lord Denman, a grateful patient, donated
      an instrument cupboard to the Volks Hospital which survives to this day. In the
      later years of the war, Dr George Pratt Yule founded the Orange River Colony
      Medical Society, which eventually led, by a very roundabout route, to the
      founding of the Medical Association of South Africa, while Ella Scarlett became
      the first woman medical practitioner in the Free State.

PMID- 9608296
TI  - Tuberculosis and anorexia nervosa.

PMID- 9608297
TI  - Latex allergy and the law.

PMID- 9608298
TI  - Frequency of HIV testing and diagnosis in a KwaZulu-Natal regional hospital.

PMID- 9608299
TI  - 'Sleep therapy' or medical malpractice?

PMID- 9608300
TI  - Medicine in South Africa--a cry from the heart.

PMID- 9608301
TI  - EEG change after fitting a posture modifying appliance.

PMID- 9608302
TI  - Vaccine-induced remission of severe chronic arthritis.

PMID- 9608304
TI  - Management of early onset severe twin-twin transfusion syndrome in the absence of
      fetoscopic equipment by exteriorisation, ligation and replacement of the
      umbilical cord of the sacrificed twin.

PMID- 9608305
TI  - The hepatitis G virus/GBV-C is associated with glomerulonephritis.

PMID- 9608306
TI  - Promoting health through schools

PMID- 9608307
TI  - Plans for vaccines

PMID- 9608308
TI  - Tuberculosis control and social development

PMID- 9608309
TI  - The essential technology package--a sine qua non for affordable and sustainable
      health care deliver?

PMID- 9608310
TI  - A cost analysis of the tuberculosis control programme in Elsies River, Cape Town
AB  - SETTING: Four primary health care clinics located in the suburb of Elsies River
      in the metropolitan area of Cape Town. AIM: To measure the cost of the
      Tuberculosis Control Programme to the health service in Elsies River and
      determine the costs associated with each of the clinic, community and self
      supervised methods of treatment of pulmonary tuberculosis patients. DESIGN: A
      cost analysis designed to assess the resource input requirements of the three
      alternative programmes of implementing the supervision of antituberculosis
      therapy. The main outcome measurement was the estimated cost per patient treated
      for the health services by three different supervision methods (clinic, self and
      community-based). RESULTS: The estimated cost per patient for a 6-month period in
      each of the supervision groups (clinic, self and community) was R3 600, R1 080
      and R720 respectively. CONCLUSION: Directly observed therapy, short-course
      (DOTS), has been adopted as the recommended policy for managing tuberculosis in
      South Africa. The costs incurred by the variety of supervision options evaluated
      in this study indicate that community-based directly observed therapy by a
      volunteer lay health worker may be less costly to the health services than either
      clinic or self supervision.

PMID- 9608311
TI  - The geographical distribution of diagnostic medical and dental X-ray services in
      South Africa
AB  - AIM: The aim of this study was threefold, viz.: (i) to evaluate the availability
      and accessiblity of medical and dental X-ray services in South Africa; (ii) to
      evaluate geographical information systems (GIS) as a tool for management of
      health care technologies; and (iii) to guide policy and develop a process to
      provide optimal utilisation of X-ray services in South Africa. METHODS:
      Information supplied by the Department of Health on licensed X-ray equipment was
      integrated with census data and processed with GIS. Four key areas were assessed,
      viz. distribution, accessibility, age and availability of X-ray services in South
      Africa. RESULTS: The analysis shows a vast inequity in the distribution of X-ray
      services on a provincial as well as a district level, although on the national
      level the distribution of X-ray services meets the World health Organisation
      criteria. CONCLUSION: GIS is a useful tool in evaluating and planning of
      essential health services/techniques. However, care must be taken in interpreting
      the data on a macro level, as this masks vast inequities on the district level.
      RECOMMENDATIONS: The indicators of coverage should be expanded, similar reports
      should be prepared for the nine provinces, and these data should be integrated
      into the clinic planning programme. Radiological services should be added to and
      managed as part of an essential district health care technology package.

PMID- 9608312
TI  - The cost implications of participatory research. Experience of a health services
      review in a rural region in South Africa
AB  - OBJECTIVES: The study objectives were to estimate the total costs incurred by a
      comprehensive review of primary health care services in a rural region in South
      Africa, and to determine which of these costs were incurred because of the
      participatory research techniques employed by the review. DESIGN: The costing
      study estimated the direct and indirect costs of each component of the review in
      order to determine total costs. Costs that were linked to participatory research
      activities were aggregated separately. SETTING: The review that was costed was
      conducted in an area that included the former 'homeland' KaNgwane and the
      adjacent areas of 'white' South Africa, in part of what is now known as
      Mpumalanga Province. SUBJECTS: Not relevant. OUTCOME MEASURES: Direct, indirect,
      total, research and participation costs were used as outcome measures. RESULTS:
      Expenditure generated by participatory research techniques was estimated to be
      almost 14% of the total (direct and indirect) costs. CONCLUSIONS: Despite these
      costs, participatory research techniques are invaluable in terms of the many
      benefits they have for a research project. However, because of these costs, it is
      important that the financing of participatory research should be carefully
      planned. Projects must budget for the direct costs of participatory techniques,
      participating organisations and individuals must be committed to bearing the
      indirect costs of participation, and, increasingly, funders must consider funding
      these indirect costs. This is important in the South African situation, where
      public health research relies increasingly on the participation of relevant
      stakeholders.

PMID- 9608314
TI  - Monitoring home births

PMID- 9608313
TI  - Tuberculosis care--what does it cost the patient?

PMID- 9608315
TI  - Biology and toxic effects of nonsteroidal anti-inflammatory drugs.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) continue to be important
      therapeutically. The development of drugs that are highly COX-2 selective has led
      to interesting new findings about their effects and potential toxic reactions.
      This year there were interesting observations about the effects of individual
      NSAIDs on the gastrointestinal mucosa, risk factors for sustaining an NSAID
      induced gastric or duodenal ulcer, and there has been progress in further
      understanding what may or may not work to prevent a toxic reaction. Furthermore,
      information has been gathered about the effects of NSAIDs on colorectal polyps
      and the development of cancers.

PMID- 9608316
TI  - Disease-modifying antirheumatic drugs.
AB  - Disease-modifying antirheumatic drug (DMARD) therapy is now clearly accepted as
      the primary treatment for rheumatoid arthritis, with an increasing emphasis on
      use of combination therapy. Data on combination therapy have highlighted the
      difficulties in performing these studies and the large number of patients
      required to produce meaningful results. Combination studies have focused on use
      of rapidly decreasing high-dose steroids as a part of the combination and
      emphasize the importance of using patients with early rheumatoid arthritis. Even
      with relatively aggressive use of DMARDs, the majority of patients develop
      erosions. Adverse reactions to DMARDs continue to concern clinicians, although
      evaluation of the frequency of these events has led to a reappraisal of
      previously accepted monitoring strategies in some cases. For example, it may not
      be cost-effective to subject patients on antimalarials to regular review by an
      ophthalmologist because of the low frequency of serious eye defects. Studies have
      also identified risk factors for the development of pulmonary toxicity in
      association with methotrexate. That DMARDs are effective in treating rheumatoid
      arthritis is beyond question-just how effective they are and what combinations of
      DMARDs will show improved efficacy will provide data for the next annual review.

PMID- 9608317
TI  - Update on immunosuppressive therapy.
AB  - In this review we summarize selected articles that have been published about
      immunosuppressive agents in the past year. These studies fall into three major
      categories: 1) use of pulse cyclophosphamide in autoimmune diseases other than
      systemic lupus erythematosus; 2) use of newer immunosuppressive agents such as
      cyclosporine and FK506 in a variety of rheumatic diseases; and 3) toxicity.

PMID- 9608318
TI  - Biologic agents in the treatment of inflammatory rheumatic diseases.
AB  - In 1997, knowledge about the treatment of autoimmune rheumatic diseases increased
      further. The most promising data to date came from studies using tumor necrosis
      factor-alpha blocking agents, such as monoclonal antibodies or soluble receptor
      constructs. Clinical trials with these compounds have now advanced to phase III;
      however, long-term safety data are not yet available. In addition, new
      developments with regard to T-helper cell-directed treatment principles, anti
      inflammatory cytokines, and adhesion molecules are discussed.

PMID- 9608319
TI  - Corticosteroids in the treatment of rheumatologic diseases.
AB  - As understanding of the role of endogenous corticosteroid production by the
      adrenal glands in rheumatologic diseases has increased, attempts to refine their
      use in accordance with this knowledge have been reported. Similarly, as
      understanding of the induction of bone loss by corticosteroids increases, trials
      of agents designed to antagonize these actions are reported. The lack of large
      scale comparative studies means that the optimal method of use of corticosteroids
      and the optimal antiresorptive protocols have yet to be defined.

PMID- 9608320
TI  - Rheumatoid arthritis.

PMID- 9608321
TI  - The genetic contribution to the pathogenesis of rheumatoid arthritis.
AB  - The association of HLA-DR4 or other HLA-DRB1 alleles excoding the shared (or
      rheumatoid) epitope has now been established in nearly every population.
      Similarly, the fact that the presence and gene dosage of HLA-DRB1 alleles affect
      the course and outcome of rheumatoid arthritis has likewise been seen in most
      (although not all) studies. Family studies are making it increasingly clear that
      other genes are involved in the pathogenesis of rheumatoid arthritis, both within
      and outside of the major histocompatibility complex, and much work is ongoing to
      help identify them and their impact on the disease. This article reviews where we
      stand in the knowledge of HLA and other genes and their associations with
      predisposition to and outcome in rheumatoid arthritis.

PMID- 9608322
TI  - Are autoantibodies active players or epiphenomena?
AB  - Autoantibodies have the potential of pathogenicity in several diseases. In
      rheumatoid arthritis (RA), however, this has not been ultimately proven. RA is
      characterized by a variety of autoantibodies. Newer insights into characteristics
      of rheumatoid factors indirectly suggest their pathogenetic involvement. In
      contrast, antibodies to collagen, despite the availability of an experimental
      model, do not appear to be pathogenetic in man. Anti-hnRNP antibodies,
      particularly anti-A2/RA33, are present in RA and experimental models of RA, and
      therefore, aside from their diagnostic value in established and early RA, could
      also be involved in the disease process. The nature of Sa, another target antigen
      in RA, has not yet been elucidated. Filaggrin is the antigen recognized by
      antikeratin antibodies and antiperinuclear factor; however, citrullin is the
      target amino acid in filaggrin, and anticitrullin antibodies have a high
      predictive value. Among a series of cartilage proteins, most have not yet been
      characterized sufficiently; one, gp39, appears to be of particular interest.
      Whether or not these antibodies are involved in RA pathogenesis is not yet known.
      It can be speculated that autoimmunity to some, if not all, of these autoantigens
      mirrors events important in the development of RA, but further studies on T-cell
      reactivities and in experimental models are needed to fully understand the
      involvement.

PMID- 9608324
TI  - Molecular biology of cartilage and bone destruction.
AB  - Molecular biology has provided various new insights into the mechanisms operative
      in the pathogenesis of rheumatoid arthritis. Reflecting the unique character of
      rheumatoid synovium, advances have been achieved addressing the molecular changes
      taking place at the area of interaction between the aggressively growing synovium
      and the articular cartilage and bone. Key issues in the review period addressing
      this interaction were hyperplasia of rheumatoid arthritis synovium, mechanisms of
      activation and cell cycle regulation of synovial fibroblasts, pathways of
      synovial attachment to cartilage and bone, and the regulation of matrix-degrading
      enzymes.

PMID- 9608323
TI  - T cells and related cytokines.
AB  - T cells play a critical role in rheumatoid arthritis. They are probably
      continuously involved in pathogenesis, from the initiation to the chronic stage.
      As recent studies have demonstrated, the part they play in rheumatoid arthritis
      is closely linked to the roles of macrophages and mesenchymal cells, because they
      all interact through autocrine, paracrine, and cell-contact pathways. This paper
      reviews recent work and research regarding the specific role of T cells in the
      pathogenesis of rheumatoid arthritis.

PMID- 9608325
TI  - Neuropeptides and steroid hormones in arthritis.
AB  - Primary afferent nociceptive and peptidergic efferent nerves are sensitized in
      arthritis and thus easily stimulated by mechanical and chemical stimuli. This
      leads to increased or disturbed release of neuropeptides from nerve terminals.
      This local (at the site of stimulation), expanded (expanded and additional
      receptive fields), and remote (cross-spinal reflexes) neuropeptide release leads
      to disturbed tissue homeostasis and neurogenic inflammation. In arthritis, raised
      levels of neuropeptides were detected in the synovial fluid, whereas nerve fibers
      were lacking in the synovial tissue. It has been hypothesized that cycles of
      nerve fiber destruction and degeneration follow the cycles of joint inflammation.
      This evidence suggests that the peripheral nervous system, through its
      neuropeptides, may contribute to the generation of inflammation, i.e.,
      "neurogenic inflammation." Altered hypothalamic-pituitary-adrenocortical axis
      function and sex hormone status have been suggested to contribute to the
      development and persistence of arthritis. In particular, current evidence
      indicates that glucocorticoid secretion is closely and reciprocally interrelated
      with inflammation, and that an adrenal insufficiency is present in many forms of
      immune-mediated arthritis. Conversely, gonadal steroids seem to play a central
      role as predisposing factors in many forms of arthritis, with estrogens involved
      as immuno-enhancing hormones and androgens as natural immunosuppressors.
      Functional receptors for sex hormones have been described in cells involved in
      the immune response and, after activation, the hormone-receptor complex might
      modulate the expression of selected cytokines. The possibility of targeting the
      efferent nerves with specific peptides and replacement therapies with selected
      steroid hormones may represent a new and potentially efficient and natural system
      of modulation of the arthritis.

PMID- 9608326
TI  - Novel therapeutic strategies involving animals, arthritis, and apoptosis.
AB  - Animal models of arthritis provide a window into the pathogenesis of inflammatory
      joint disease. In addition, they can function as an in vivo laboratory for
      evaluating new and creative treatments. The potential usefulness of novel
      treatment strategies, including recombinant cytokine therapy, gene delivery, and
      regulation of apoptosis, have been explored and offer clues to the feasibility of
      human therapeutic trials. New models of arthritis have also been developed in an
      effort to increase the predictive capacity for efficacy in rheumatoid arthritis.

PMID- 9608327
TI  - Osteoarthritis and crystal deposition diseases.

PMID- 9608328
TI  - Quadriceps weakness in osteoarthritis.
AB  - Involvement of the quadriceps muscle group in knee osteoarthritis is receiving
      increasing research interest. The motor and sensory functions of muscle are
      intimately linked, and deficits in the sensorimotor functions of the quadriceps
      have been identified and proposed as possible factors in the pathogenesis of knee
      osteoarthritis or as consequences of the disease. Weakness of the quadriceps as a
      clinical feature of knee osteoarthritis has been well recognized for some time,
      but causes for this weakness and its significance as a determinant of the
      patient's disability is only now being investigated. Rehabilitation regimens that
      increase quadriceps weakness also effect improvements in the patient's
      disability, but the length and cost most of these research regimens would be
      impractical in the clinical setting. More clinically practicable rehabilitation
      regimens need to be devised that could be implemented in the community, if the
      management of this chronic, prevalent condition is to be managed effectively and
      cost-effectively.

PMID- 9608329
TI  - Neurogenic acceleration of osteoarthritis.
AB  - The nervous system has a variety of mechanisms whereby it can potentially
      initiate or accelerate joint disease. Whether these potential mechanisms are
      clinically significant factors in the etiology of osteoarthritis remains
      uncertain. However, 11 papers published in the past year provide further support
      for the view that these mechanisms are important in the pathogenesis of the
      disease.

PMID- 9608330
TI  - The importance of subchondral bone in osteoarthrosis.
AB  - This article reviews evidence that subchondral bone plays a role in the
      degeneration of cartilage in osteoarthrosis. Whether the bony changes precede the
      cartilage degeneration remains unproven but may best be considered necessary for
      progression of the disease. Epidemiologic studies clearly show increasing
      subchondral sclerosis with disease progression. Recent evidence demonstrates
      specific architectural changes in the subchondral trabecular bone in
      osteoarthrosis that are consistent with an acceleration of bone turnover, which
      appears to be a part of the pathophysiologic process in progression of the
      disease. The now well-documented acceleration of bone turnover in osteoarthrosis
      decreases the stiffness of the bone as a material, but because of structural
      modifications in both trabecular bone (i.e., increased trabecular number and
      reduced separation) and subchondral bone (i.e., increased plate thickness), the
      stiffness (rigidity) of the structure as a whole undoubtedly increases. There is
      no evidence that growth factors, cytokines, or enzymes play any role in the bony
      changes associated with the disease, other than as the naturally occurring
      sequelae of normal bone remodeling processes.

PMID- 9608331
TI  - The role of nitric oxide in articular cartilage breakdown in osteoarthritis.
AB  - It is increasingly appreciated that mediators typically associated with
      inflammatory arthritis, such as catabolic cytokines and nitric oxide, are
      produced by synovium and cartilage in osteoarthritis. The role that such
      mediators play in the progression of cartilage degradation in osteoarthritis is
      under intensive investigation. Nitric oxide is a highly reactive, cytotoxic free
      radical that has been implicated in tissue injury in a variety of diseases.
      Cartilage obtained from patients with osteoarthritis produces significant amounts
      of nitric oxide ex vivo, even in the absence of added stimuli such as interleukin
      1 or lipopolysaccharide. In vitro, nitric oxide exerts detrimental effects on
      chondrocyte functions, including the inhibition of collagen and proteoglycan
      synthesis, enhanced apoptosis, and an inhibition of B1 integrin-dependent
      adhesion to the extra-cellular matrix. This paper reviews recent observations
      regarding the role of nitric oxide in osteoarthritis and presents evidence
      suggesting that the inhibition of nitric oxide production could be a desirable
      future therapeutic strategy.

PMID- 9608332
TI  - The effects of estrogen on osteoarthritis.
AB  - The prevalence of osteoarthritis is higher in women than men, and in women it
      increases dramatically in the years after menopause. These observations and
      others reporting a painful form of hand osteoarthritis after the menopause
      suggest that loss of estrogen at the time of menopause increases a woman's risk
      of getting osteoarthritis. This article reviews biologic evidence for hormone
      sensitivity of cartilage, animal studies testing the effect of estrogen on the
      joints of ovariectomized animals, and human epidemiologic and clinical studies
      evaluating endogenous estrogen levels and estrogen replacement therapy and their
      relation to the occurrence of osteoarthritis. Overall the evidence for a role of
      estrogen in osteoarthritis is conflicting. Epidemiologic studies of women who
      take estrogen replacement therapy, however, consistently report that these women
      have a lower prevalence of osteoarthritis than women not taking estrogen,
      suggesting a possible therapeutic role for estrogen in osteoarthritis.

PMID- 9608333
TI  - Calcium crystal-associated arthritides.
AB  - Articular calcium-containing crystals cause calcium pyrophosphate dihydrate
      (CPPD) deposition disease, basic calcium phosphate (BCP)-associated syndromes,
      and calcium oxalate arthritis. During the past year, important contributions have
      been made to our understanding of CPPD- and BCP-related syndromes. Clinical
      studies of CPPD deposition disease underscore the importance of extra-articular
      and spinal CPPD deposits, and question the association between hypothyroidism and
      chondrocalcinosis. Laboratory reports add key information to our current
      paradigms of CPPD crystal formation and CPPD-induced inflammation. Several
      interesting new therapeutic interventions may arise from this work. A case
      collection of BCP-related syndromes emphasizes the need for considering this
      diagnosis in young healthy patients with acute arthritis or periarthritis.

PMID- 9608334
TI  - Clinical therapeutics.

PMID- 9608335
TI  - Osteoarthritis and crystal deposition diseases.

PMID- 9608336
TI  - A dermatologic diary. Portrait of a new life.

PMID- 9608337
TI  - Hormonal influences on women with psoriasis.
AB  - Various endogenous factors such as stress and infection are known to influence
      psoriasis. Previous data suggest that pregnancy has a significant influence on
      the course of psoriasis. This study explores the effect of pregnancy as well as
      other hormonal events on psoriasis in women.

PMID- 9608338
TI  - Papular acrodermatitis of childhood related to poxvirus and parvovirus B19
      infection.
AB  - Papular acrodermatitis of childhood (Gianotti-Crosti syndrome) is considered an
      unspecific cutaneous pattern related to an increasing number of infectious
      diseases. We report two cases of Gianotti-Crosti syndrome, one of which occurred
      in the setting of parvovirus B19 primary infection and the other followed
      poxvirus infection. Parvovirus B19 and poxvirus may represent new causative
      agents of Gianotti-Crosti syndrome.

PMID- 9608339
TI  - Unusual patterns of chronic photodamage through clothing.
AB  - Recent cancer statistics estimate that the yearly incidence of cutaneous
      malignancies in the United States is similar to the incidence of all other
      cancers combined. Ultraviolet radiation-induced photodamage of the skin plays a
      large role in the growth of these skin cancers. The case of a 47-year-old white
      man with peculiar patterns of actinic skin damage on the anterior chest and back
      is presented, and the relationship of these findings with his choice of clothing
      is reviewed. The transmission of ultraviolet radiation through clothing fabrics
      is addressed, with recommendations for the use of clothing as an effective form
      of photoprotection.

PMID- 9608340
TI  - Desmoplastic malignant melanoma presenting as an erythematous nodule tumor.
AB  - Desmoplastic malignant melanoma is an uncommon neoplasm that presents both as a
      clinical and diagnostic challenge. Prognosis is frequently adversely affected by
      misdiagnosis and delayed diagnosis of this tumor, which is often amelanotic. We
      report a case of an amelanotic desmoplastic malignant melanoma that presented as
      an erythematous nodular tumor.

PMID- 9608341
TI  - Dark oral lesions: differential diagnosis with oral melanoma.
AB  - Oral melanoma is a neoplasm with a poor prognosis; its premature diagnosis is of
      foremost importance. We review here pathologic situations to be considered in the
      clinical differential diagnosis: tattoos, melanotic macules, Laugier's disease,
      melanocytic nevus, drug intake, some vascular lesions, and oral pigmented lesions
      associated with endocrine disorders or with different syndromes.

PMID- 9608342
TI  - Acute hemorrhagic edema of infancy: Finkelstein's disease.
AB  - Acute hemorrhagic edema of infancy (AHEI) is a benign form of leukocytoclastic
      vasculitis limited to the skin, which occurs in children younger than 2 years of
      age. The abrupt onset of fever, peripheral edema, and purpuric targetoid plaques
      in an infant may be confused with other dermatoses such as Henoch-Schonlein
      purpura, Sweet's syndrome, erythema multiforme, or septic vasculitis. Laboratory
      studies of patients with AHEI typically show normal results and the disorder
      follows a benign course with spontaneous resolution occurring in 1 to 3 weeks. We
      present a case of AHEI occurring in a 7-month-old boy and review the
      characteristic features of this acute dermatosis.

PMID- 9608343
TI  - Melanoma arising in nevus spilus.
AB  - Nevus spilus is a pigmented skin lesion composed of a pigmented macule on which
      darker lesions appear at a later stage. There are an increasing number of reports
      of malignant melanoma occurring within these lesions, leading to greater concern
      regarding the malignant potential of these lesions. We describe the case of a
      fatal malignant melanoma arising in a congenital nevus spilus.

PMID- 9608344
TI  - Morphine-conditioned changes in locomotor activity: role of the conditioned
      stimulus.
AB  - When a multisensory environment was reliably paired with morphine (2 mg/kg) in
      rats, that environment, in a drug-free test, evoked a hyperactive conditioned
      response (CR). When an olfactory cue (banana odor) was the only stimulus element
      reliably paired with morphine, it also elicited a hyperactive CR. However, a
      gustatory cue (saccharin solution) evoked a hypoactive CR. This taste-elicited
      decrease in activity was dose dependent; morphine at 2 and 4 mg/kg conditioned
      hypoactivity, whereas a higher dose (8 mg/kg) did not. A robust conditioned
      saccharin aversion occurred only at the highest dose of morphine, suggesting
      disassociation between the hypoactive CR and taste aversion. A taste cue present
      during context conditioning also prevented either acquisition or expression of
      the hyperactive CR to the context. The modality of the conditioned stimulus is a
      critical determinant of the form of the CR in a morphine locomotor conditioning
      paradigm.

PMID- 9608345
TI  - Drug discrimination history: pigeons trained to discriminate opioids with
      activity at different receptor types.
AB  - In pigeons (Columba livia; N = 5) trained to discriminate the mu (mu) opioid
      butorphanol from saline, various mu (morphine, fentanyl) but not kappa (kappa;
      bremazocine, U50,488, U69,593) opioids produced at least 80% drug-appropriate
      responding. Subsequently, pigeons were retrained to discriminate the kappa opioid
      bremazocine from saline; in this condition, both mu and kappa opioids produced at
      least 80% drug-appropriate responding, naloxone was more potent as an antagonist
      of the butorphanol stimulus, and chronic bremazocine treatment selectively
      produced tolerance to the bremazocine stimulus. Although butorphanol can function
      as a kappa antagonist, the effects produced by combinations of butorphanol and
      bremazocine during training with bremazocine were generally effect-additive. The
      findings indicate that the mechanisms underlying the stimulus effects of mu
      opioids are not altered by subsequent training with a kappa opioid. Conversely, a
      history of discrimination training with a mu opioid does not alter the
      discriminative control produced by kappa opioids during subsequent training with
      a kappa opioid.

PMID- 9608346
TI  - Predicting the emergence and persistence of alcohol dependence in young adults:
      the role of expectancy and other risk factors.
AB  - The relationship of alcohol outcome expectancies and other risk factors:
      demographic, personality, and affectivity, to alcohol dependence status was
      examined over a 3.5-year interval in 1,007 young adults. Lifetime prevalence of
      alcohol dependence was 18.1% at baseline. Of persons classified as current
      alcohol dependent at baseline, 66.9% experienced remission at the 3.5-year follow
      up. Of persons classified as remitted alcohol dependent at baseline, 11.3% were
      current alcohol dependent at the 3.5-year follow-up. At follow-up, 5% of persons
      with no history of alcohol dependence at baseline met criteria for current
      alcohol dependence. Male gender, higher extraversion, and lower positive affect
      scores predicted emergent current alcohol dependence at the 3.5-year interval.
      Persistent current alcohol dependence was predicted by the expectation of
      improved social and sexual experiences following alcohol use. The findings
      suggest that positive expectancies may be an important factor in persistence of
      alcohol dependence and that their modification may enhance treatment of alcohol
      dependence in young adults.

PMID- 9608347
TI  - Use of monetary reinforcement to reduce the cigarette smoking of persons with
      schizophrenia: a feasibility study.
AB  - The feasibility of using monetary reinforcement to promote abstinence from
      substance use in adult individuals with schizophrenia was addressed. Cigarette
      smoking was studied as an exemplar of drug use in 11 individuals with
      schizophrenia by use of a within-subject experimental design. The study duration
      was 3 weeks, with weeks 1 and 3 serving as baseline conditions and week 2 serving
      as the intervention condition; in the latter, patients could earn money by
      abstaining from cigarette smoking. Abstinence was significantly greater during
      the intervention condition than during the baseline conditions. These results
      illustrate the potential sensitivity of drug use in this population to
      reinforcement contingencies, suggesting that contingency-management interventions
      are a feasible option for treating the substance abuse of individuals with
      schizophrenia.

PMID- 9608348
TI  - Medication take-home doses and contingency management.
AB  - Two studies examined contingent take-home medication doses during treatment of
      opiate or cocaine dependence. In the first study, methadone maintenance patients
      were randomly assigned to one of two 8-week baseline take-home (TH) conditions
      differing in frequency of clinic visits per week. This was followed by a 12-week
      contingency management (CM) procedure in which frequent THs resulted from drug
      free urines. Participants receiving more frequent THs during baseline had lower
      illicit drug use during the first 6 weeks of CM. In the second study, fluoxetine
      (0-, 20-, 40-mg) TH doses were similarly contingent in treatment of cocaine
      dependence. The 40-mg group used less cocaine during contingency than did other
      groups. The combination of fluoxetine and environmental contingencies may produce
      benefit where neither alone is sufficient.

PMID- 9608349
TI  - Hydromorphone-naloxone combinations in opioid-dependent humans under a naloxone
      novel-response discrimination procedure.
AB  - Naloxone-hydromorphone combinations were tested in participants trained to
      discriminate naloxone from placebo under a novel-response drug discrimination
      procedure while maintained on methadone. Naloxone alone produced dose-related
      increases in naloxone-appropriate responding, little or no "novel"-appropriate
      responding, and increases in opioid antagonist adjective ratings (n = 5).
      Hydromorphone alone produced dose-related increases in novel-appropriate
      responding, little or no naloxone-appropriate responding, and increases in opioid
      agonist adjective ratings (n = 6). When combined with naloxone, hydromorphone
      produced dose-related decreases in naloxone-appropriate responding and antagonist
      adjective ratings (n = 6). These findings are consistent with nonhuman data and
      suggest that this procedure may be useful as a human laboratory model of opioid
      withdrawal.

PMID- 9608350
TI  - Scripted imagery manipulations and smoking cue reactivity in a clinical sample of
      self-quitters.
AB  - The affectively valenced scripts used by S. Tiffany (1990) suggest that different
      scripts produce relatively equivalent levels of cue reactivity, although it is
      unclear if these laboratory findings generalize to clinical samples. In this
      study, cessation-motivated smokers were tested 7 days before they tried to quit
      smoking and were exposed to 3 audiotaped scripts that depicted different
      affectively valenced situations (neutral, positive, or negative). The latter 2
      scripts also contained smoking cues. The findings using a clinical sample
      differed considerably from those using analogue laboratory samples across
      affective, cognitive, and physiological response measures. Reactivity to these
      standardized scripts failed to predict treatment outcome through a 30-day follow
      up. The use of affectively valenced scripts beyond a laboratory sample is
      questioned.

PMID- 9608351
TI  - Dosage effects of methylphenidate on the social behavior of adolescents diagnosed
      with attention-deficit hyperactivity disorder.
AB  - Research participants were 46 adolescents (mean age = 13.8 years) who completed
      an intensive summer treatment program including a placebo-controlled, double
      blind, crossover trial of 3 doses of methylphenidate (MPH) totaling 25, 50, or 75
      mg per day. Dependent measures focused on social behavior and included observed
      behavior frequencies and ratings completed by counselors and parents, including
      side effects. Multiple data analytic methods were used with the goal of (a)
      describing the shape of the dose-response curves across multiple measures of
      social functioning, (b) determining the percentage of adolescents whose social
      behavior improved in response to MPH, and (c) assessing the incremental gains
      that result from increases in dose. The results show that (a) the shape of the
      dose-response curve is influenced by the measurement method, (b) the majority of
      adolescents exhibited improved social behavior when treated with MPH, (c) the
      bulk of the positive effects of MPH were achieved at the lowest dose, and (d)
      there appear to be diminishing positive effects and an increased risk of negative
      effects with successively higher doses.

PMID- 9608352
TI  - Differentiating withdrawal patterns between smokers and smokeless tobacco users.
AB  - The present study was designed to document smokeless tobacco withdrawal patterns
      and to examine differential withdrawal responses between smokers and smokeless
      users. Participants (N = 19) were studied under deprivation and nondeprivation
      conditions, 1 condition per week. The Withdrawal Symptoms Checklist was
      administered to assess cognitive and affective changes. Both smokers and
      smokeless users experienced substantially more withdrawal at 48-hr deprivation
      compared to the 48-hr nondeprivation condition. Participants in both groups
      endorsed decreasingly fewer withdrawal symptoms from 0 hr to 48 hr on
      nondeprivation days. This downward trend suggests a need for stabilizing
      withdrawal responses before deprivation.

PMID- 9608353
TI  - Importance of environmental distractors in the effects of nicotine on short-term
      memory.
AB  - This study examined the role of environmental context in mediating the effects of
      nicotine on short-term memory performance (i.e., working memory). Male and female
      smokers (n = 12, overnight tobacco abstinent) and nonsmokers (n = 11) were
      administered nicotine (20 ug/kg) and a placebo (0 ug/kg) by means of a measured
      dose nasal spray procedure on separate days. Participants were tested on a
      variant of S. Sternberg's (1966) memory search task. Half of the memory task sets
      involved the presentation of an auditory environmental distraction. Improvements
      in short-term memory performance with nicotine were primarily seen in smokers and
      in the presence of the distracting stimuli. These results suggest that
      environmental conditions, such as the presence of a distracting stimulus, may
      play an important role in mediating the effects of nicotine.

PMID- 9608354
TI  - Cocaine use is associated with increased craving in outpatient cocaine abusers.
AB  - Sixty-one cocaine abuse patients provided self-reports of craving and urine
      samples 3 times a week. Within-subject analyses revealed several relationships
      between the measures. First, peak craving levels were higher for 2-3-day
      intervals during which cocaine use had occurred than for preceding or following
      abstinent intervals. Second, average craving ratings during cocaine use intervals
      were double the ratings given during abstinent intervals. Third, cocaine use was
      4 times more likely to occur during a period of elevated craving than during
      comparison intervals. Finally, participants who provided at least 1 positive
      urine sample reported more craving increases over 4 weeks than did abstinent
      individuals. These results demonstrate a strong association between craving
      increases and naturally occurring cocaine use but do not allow a determination of
      whether craving caused cocaine use or cocaine use caused craving.

PMID- 9608355
TI  - Structure and linkage relationships of the region containing the human L-type
      pyruvate kinase (PKLR) and glucocerebrosidase (GBA) genes.
AB  - Both the L-type pyruvate kinase gene (PKLR) and glucocerebrosidase (GBA) gene are
      on band q21 of chromosome 1 in humans. Two overlapping P1 bacteriophage clones
      containing PKLR and GBA were identified and mapped, defining the locations of
      these two genes as well as those of the GBA pseudogene (psi GBA) metaxin (MTX),
      the MTX pseudogene (psi MTX), and thrombospondin 3 (THBS3). The distance between
      the 5' ends of GBA and PKLR was determined to be 71 kb. The direction of
      transcription PKLR gene was convergent to that of the GBA gene. All 195 Gaucher
      disease patients homozygous for the 1226G mutation, representing 390 chromosomes
      with the 1226G mutation, had a PvuII -/- GBA haplotype and a C/C at nt 1705 of
      the PKLR gene (-/- haplotype). All 56 Gaucher disease patients who were
      1226G/84GG compound heterozygotes manifested a -/+ GBA haplotype and 55 of 56
      patients were -/+ at PKLR nt 1705. Only 1 patient with 1226G/84GG genotype showed
      a crossover with the PKLR polymorphism, with a -/- haplotype at nt 1705.
      Similarly, 9 patients deficient in pyruvate kinase with the PKLR 1529A/1529A
      genotype were all found to have the same -/- GBA haplotype.

PMID- 9608356
TI  - Amplification of T-cell receptor alpha- and beta-chain transcripts from mouse
      spleen lymphocytes by the nonpalindromic adaptor-polymerase chain reaction.
AB  - We employed the nonpalindromic adaptor-PCR (NPA-PCR) method to amplify T-cell
      receptor (TCR) alpha- and beta-chain transcripts from the spleen of normal SJL
      mice. The NPA-PCR method has been specifically designed for the amplification of
      transcripts with variable or unknown 5' ends, such as TCRs and immunoglobulins
      (Ig). This method has certain distinct advantages over existing two-sided PCR
      methods for the amplification of TCR transcripts. Two NPA-PCR amplifications are
      sufficient to amplify all the TCR transcripts (one for the alpha-chain and
      another one for the beta-chain). Amplification of TCR transcripts by classical
      two-sided PCR requires a minimum of 45 amplification reactions for the murine TCR
      (20 for the V alpha families and 25 for the V beta families), using 45 different
      V-family-specific amplification primers. cDNA was synthesized from spleen RNA,
      using oligonucleotides complementary to sequences of either the murine TCR C
      alpha or C beta regions. The NotI restriction site was conjugated to these
      primers and therefore, a NotI restriction site was incorporated at the 3' end of
      the cDNA. A double-stranded nonpalindromic adaptor (EcoRI-XmnI strand and XmnI G
      strand, which are complementary to each other) was ligated onto both ends of the
      double-stranded cDNA. The adaptor was removed from the 3' end by NotI nuclease
      digestion whereas the adaptor was retained at the 5' end. Two rounds of PCR
      amplification were carried out. In the first, the EcoRI-XmnI adaptor was used as
      5' end amplification primer; an antisense C region primer, designated mC alpha 2
      or mC beta 2 (for the alpha- and beta-chain, respectively), was used as 3'
      amplification primer. In the second round of PCR amplification the same 5' end
      primer and a 3' end antisense primer, designated mC alpha 1 or mC beta 1, were
      used. These mC alpha 1 and mC beta 1 primers are located 5' to the mC alpha 2/mC
      beta 2 primers that were used for the first amplification. The amplified
      transcripts were cloned. Colonies were screened using a 32P-labeled probe, either
      C alpha or C beta, located 5' to those used for the last amplification and many
      positive clones were isolated and sequenced. All clones were unique when compared
      to each other, as anticipated for polyclonal T-cell populations. Comparison of
      the sequences obtained to those in the GENBANK/EMBL database revealed that they
      were typical of mouse alpha- or beta-chain TCR. With the exception of two beta
      chain TCR transcripts, all the sequences shown here (36 alpha-chain and 20 beta
      beta chain) have not been previously reported to the GENBANK/EMBL database.

PMID- 9608357
TI  - Thiol compounds rescue growth inhibition by retinoic acid on HTLV-I (+) T
      lymphocytes; possible mechanism of retinoic-acid-induced growth inhibition of
      adult T-cell leukemia cells.
AB  - We demonstrated significant growth inhibition by retinoic acid (RA) of HTLV-I (+)
      T-cell lines (ATL-2 and HUT102), but not HTLV-I (-) T-cell lines (MOLT-4 and
      Jurkat). We hypothesized that the mechanism of growth inhibition by RA depends on
      an imbalance in redox potential. To examine the effect of exogenous thiol
      compounds for the growth of HTLV-I (+) T-cell lines by RA, HTLV-I (+) T-cell
      lines were cultured with several thiol compounds (thioredoxin, L-cystine, and
      GSH), following addition of 13-cis RA or ATRA, respectively, in cultured with
      thiol free medium. Unexpectedly, thiol compounds alone did not restore growth
      inhibition of HTLV-I (+) T-cell lines. However, when those cells were
      preincubated with thiol compounds for 24 hours, no growth inhibition by 13-cis RA
      or ATRA was observed. These results suggest that thiol compounds are associated
      strongly with sensitivity to RA of HTLV-I (+) T cells, but not of HTLV-I (-) T
      cells and that thiol compounds serve an important role on HTLV-I (+) T cells.

PMID- 9608358
TI  - Fulminant metastatic melanoma complicated by a microangiopathic hemolytic anemia.
AB  - A 34-year-old male acutely presented with widely disseminated malignant melanoma,
      a microangiopathic hemolytic anemia, and disseminated intravascular coagulation.
      Although the patient had a history of intense childhood exposure to ultraviolet
      light and an occupational exposure to organic dyes, he had no history of a
      precursor skin lesion. The histopathology of the patient's bone marrow revealed
      sheets of malignant cells immunoreactive with S-100, HMB-45, and vimentin and
      also staining positively for melanin. A bone marrow aspirate revealed myeloid
      precursors filled with melanin-bearing vacuoles. Immunophenotypic analysis of the
      patient's bone marrow by flow cytometry revealed a paucity of hematopoietic
      cells. A karyotypic analysis of the patient's tumor cells demonstrated an
      abnormal hypertriploid composite clone characterized by multiple numerical and
      structural abnormalities. Although the patient was treated aggressively with
      transfusional support, heparin, and chemotherapy, he expired 3 weeks after
      diagnosis. This is the first recognized case of metastatic melanoma occurring in
      association with a microangiopathic hemolytic anemia.

PMID- 9608359
TI  - Intranasal administration of demopressin (DDAVP) for type 1 and type 2A von
      Willebrand disease.
AB  - Desmopressin was administered intranasally to seven patients with von Willebrand
      disease (type 1: 4 patients, type 2A: 3 patients) to assess the response and
      safety. von Willebrand factor antigen ranged from 8% to 60% before treatment and
      increased significantly after intranasal DDAVP administration (the median
      relative increase: two- to threefold). Factor VIII levels also increased
      substantially over baseline levels after intranasal administration. Before
      treatment ristocetin cofactor activity was 32 +/- 12% in patients with type 1 vWD
      and 9 +/- 5% in patients with type 2A vWD. After intranasal administration, the
      levels of ristocetin cofactor activity increased to 56 +/- 21% and 29 +/- 9%,
      respectively. The bleeding time was normalized in 86% of the patients. The
      abnormality of vWF multimers in type 1 vWD returned more or less to normal after
      intranasal DDAVP administration whereas that in type 2A vWD did not. The
      intranasal administration of DDAVP is safe and effective for minor bleeding
      episodes and is adaptable for home use in patients with type 1 and type 2A vWD.

PMID- 9608360
TI  - Enzymatic and kinetic properties of blood coagulation factor XIIIa and guinea pig
      liver transglutaminase utilizing (6-[N-(4-aminobutyl)-N-ethylamino]-2,3
      dihydrophthalazine-1,4-dione, as a novel, specific and sensitive chemiluminescent
      substrate.
AB  - A novel and sensitive chemiluminescent assay is described to quantitate the acyl
      transfer activities of blood coagulation factor XIIIa or liver transglutaminase
      using aminobutyl-N-ethylisoluminol as acyl acceptor and N,N-dimethylcasein, human
      plasma fibrinogen or fibronectin as acyl donors. The method involved covalently
      linking aminobutyl-N-ethyl-isoluminol through its free amino group with the gamma
      carboxamide of protein-bound glutamine resulting in an isopeptide bond; a
      reaction catalysed by both transglutaminase and factor XIIIa. The protein-bound
      aminobutyl-N-ethyl-isoluminol was separated from non-conjugated amine by
      precipitation with trichloroacetic acid. The protein-amine conjugate was
      dissolved in 500 mmol/L NaOH, oxidized using 15 mmol/L ammonium persulphate and
      light emission quantitated using a luminometer. Optimal conditions were
      established to detect factor XIIIa and transglutaminase activities with the
      chemiluminescent assay. Specificity was demonstrated by lack of activity in the
      presence of ethylenediamine tetra-acetic acid or unactivated factor XIII, or
      boiled enzymes, and by competitive inhibition with putrescine and 5'
      (biotinamido) pentylamine. The enzymatic and kinetic properties of factor XIIIa
      and transglutaminase in utilizing aminobutyl-N-ethyl-isoluminol as an acyl
      acceptor substrate were comprehensively documented. The reaction could be carried
      out in either a purified system or a complex plasma or cell lysates milieu. The
      assay is sensitive, specific, and eliminates a need for radioactive reagents. The
      assay could be used to photolabel reactive glutamines in substrates. The assay
      could also be adapted to a variety of solid- and solution-phase formats and is
      amenable to X-ray film and/or light photography imaging.

PMID- 9608361
TI  - Chemiluminescence of cereal products II. Chemiluminescence spectra.
AB  - Spectra of ultraweak chemiluminescence (CL) accompanying auto-oxidation and
      hydration of cereal products have been measured using single photon counting and
      cut-off filters. The spectra cover the 380-880 nm spectral range with maxima
      centred around 600 nm. Analytically pure air-dried carbohydrates like agar,
      cellulose and nitrocellulose give emission too weak for spectral measurements.
      The emission from water pure carbohydrates is on average 4-12 times higher and
      emission spectra are similar to those from cereal products. The effect of free
      radical scavengers, SOD and O2* (1 delta g)-quenchers on CL spectra indicates a
      contribution of radical reactions with the participation of excited carbonyls, O2
      and excited molecular oxygen dimoles. Moreover, possible mechanisms of chemi
      excitation due to a cooperative H-bond formation during the hydration of
      carbohydrates and/or recombination of trapped radicals and electron-holes are
      discussed. It is also postulated that the excitation energy transfer to natural
      sensitizers occurring in cereal products may account for non-specific broad
      spectra and differences in the intensity of CL.

PMID- 9608362
TI  - Chemiluminescence of cereal products III. Two-dimensional photocount imaging of
      chemiluminescence.
AB  - Two-dimensional (2-D) spatial distributions of ultra-weak chemiluminescence
      (photon imaging) from auto-oxidizing and water-hydrated cereal food products were
      measured by means of a high-sensitivity 2-D photon counting system--an
      intensified charge coupled device (CCD) camera. The 2-D images obtained reveal
      the dynamics and emission patterns of very slow auto-oxidation reactions and much
      faster processes of water penetration into cereal products. The enhancement of
      chemiluminescence by the addition of water appears to involve complex processes
      with an inhomogenous spatial and energy distribution within cereal products. The
      effect of antioxidants, free radical promoters and scavengers suggests that
      oxidative radical reactions contribute significantly to the observed
      chemiluminescence. The possible involvement of hydrophilic interactions, H2O
      biopolymers and recombination of trapped radicals is also discussed.

PMID- 9608363
TI  - Chemiluminescent derivatization of adenyl compounds with glyoxal derivatives in
      the presence of heteropoly acids and its application to the simple and sensitive
      determination of DNA.
AB  - A chemiluminescence (CL) determination of adenyl compounds is described. CL
      derivatization of adenyl compounds with methylglyoxal dimethyl acetal was
      performed in the presence of tungstosilicic acid and propan-2-ol. CL from adenyl
      compounds was produced by hydrogen peroxide and L-cysteine ethyl ester in DMF and
      water. The proposed method is highly sensitive and specific to compounds
      containing adenine. Adenine was determined in the range 1.0 x 10(-3)-5.0 x 10(-8)
      M with the detection limit of 3.0 x 10(-8) M (150 fmol per assay). The method was
      applied to the determination of DNA and detection limits of a few nanograms of
      DNA achieved.

PMID- 9608364
TI  - An acridinium sulphonylamide as a new chemiluminescent label for the
      determination of carboxylic acids in liquid chromatography.
AB  - The synthesis of a new acridinium sulphonylamide label for the liquid
      chromatographic determination of carboxylic acids is described. The label 10
      methyl-N-(p-tolyl)-N-(p-iodoacetamidobenzenesulphonyl)-9-acr idi nium carboxamide
      iodide is synthesized from 9-acridine-carboxylic acid by a seven-step reaction.
      Ibuprofen, used as test compound, is coupled to the reactive iodoacetamide group
      of the label by means of an alkylation reaction in dry acetonitrile for 20 min at
      50 degrees C in the presence of 18-crown-6 and potassium carbonate as base
      catalyst. The reaction mixture is injected into a liquid chromatographic system
      with chemiluminescence detection. Separation is performed on a Zorbax C18 column
      with acetonitrile-water-tetrahydrofuran (39:57:4, v/v/v) containing 10 mmol/L
      TBABr and 0.035% H2O2 as the mobile phase at a flow rate of 1.0 ml/min.
      Chemiluminescence detection is achieved by the post-column addition of 200 mmol/L
      potassium hydroxide dissolved in methanol-water (1:1, v/v) at a flow rate of 20
      microL/min. The detection limit (S/N = 3) of derivatized ibuprofen is 60 pg (3 pg
      injected).

PMID- 9608365
TI  - Breast masses: color Doppler, power Doppler, and spectral analysis findings.
AB  - PURPOSE: To determine the diagnostic efficacy of power Doppler sonography (PDS)
      with spectral analysis for breast diseases, we retrospectively compared PDS and
      color Doppler sonography (CDS) in patients with breast lesions. METHODS: One
      hundred thirty-eight women with palpable breast lesions were examined with PDS
      (65 women) and/or CDS (73 women). We calculated peak velocity, end-diastolic
      velocity, pulsatility index (PI), and resistance index (RI). RESULTS: On a 4
      point subjective visual vascularity scale, PDS demonstrated higher vascularity
      than did CDS. Although smaller and more subtle vessels could be detected only
      with PDS, the PI and RI differed significantly between malignant and benign
      lesions when either PDS or CDS was used. However, logistic regression analysis
      showed that high PI and RI were associated with malignancy only when CDS was
      used. When PDS was used, PI was significantly higher in invasive ductal
      carcinomas with fibrous stroma and ill-defined margins (associated with a poor
      prognosis) than in invasive ductal carcinomas without fibrous stroma or with well
      defined margins. CONCLUSIONS: Doppler spectral analysis of malignant breast
      lesions using PDS may contribute to the determination of prognosis.

PMID- 9608366
TI  - Doppler assessment of the maternal interlobar renal and uterine arteries in mid
      pregnancy in women at low and high risk for pregnancy-induced hypertension.
AB  - PURPOSE: The purpose of this study was to examine the relationship between
      vascular resistance of the maternal intrarenal arteries and the main uterine
      arteries in pregnant women at low and high risk for pregnancy-induced
      hypertension. METHODS: The resistance indices (RIs) in the main uterine arteries
      and the interlobar branches of the right renal artery were measured by duplex
      Doppler sonography in 338 pregnant women at 21-24 weeks of gestation, including
      175 women at high risk for pregnancy-induced hypertension. Of those, 54 patients
      had repeat Doppler measurements during pregnancy. RESULTS: Cross-sectional data
      showed no correlation between the RIs in the right interlobar renal arteries and
      either uterine artery. Furthermore, no relationship existed between persistent
      diastolic notching in the uterine arteries and the RI in the renal circulation.
      The mean renal artery RI was 0.62. Compared to that in patients with a normal
      outcome, the renal artery RI was not significantly different in patients who
      developed proteinuric pregnancy-induced hypertension (PPIH) or severe pregnancy
      induced hypertension (PIH) later during pregnancy. Multiple analysis of variance
      for longitudinal data showed no correlation between the RI in the maternal renal
      arteries and gestational age, severe PIH, or PPIH. CONCLUSIONS: The RIs in the
      maternal intrarenal arteries and the main uterine arteries are not related to
      each other in pregnant women, even in patients with abnormal uterine artery
      Doppler findings, severe PIH, or PPIH.

PMID- 9608367
TI  - Doppler flow characteristics in patients with pelvic inflammatory disease:
      responders versus nonresponders to therapy.
AB  - PURPOSE: The objective of this retrospective study was to evaluate the role of
      Doppler flow studies in predicting the response to antibiotic treatment in
      patients with pelvic inflammatory disease (PID). METHODS: The resistance indices
      in pelvic masses of 24 patients with clinical diagnoses of PID were analyzed.
      RESULTS: Twelve patients responded favorably to antibiotic treatment (the
      conservative treatment group), while the other patients showed no clinical
      improvement and underwent surgery (surgical treatment group). The mean resistance
      index in the conservative treatment group was significantly higher (0.60 +/-
      0.15) than that in the surgical treatment group (0.52 +/- 0.08; p < 0.05).
      CONCLUSIONS: In keeping with hyperemia of inflammation, fallopian arterial
      resistance seems to decrease with the severity of PID.

PMID- 9608368
TI  - Kidney length in postoperative acute renal failure.
AB  - PURPOSE: The aim of this study was to evaluate kidney length in patients with
      postoperative acute renal failure (PARF). METHODS: The effect of PARF on renal
      size was prospectively studied in 76 patients with PARF and 40 healthy
      volunteers. Sonographic measurements of kidney length and the level of serum
      creatinine were obtained each day patients stayed in our surgical intensive care
      unit. These measurements were done once in volunteers. All study subjects were
      divided into groups on the basis of age, those younger than 65 years and those 65
      years or older. Statistical analyses on the relation of renal size, age, and
      degree of PARF used the kidney length:body height ratio (KBR) and the peak serum
      creatinine level. Follow-up kidney length and creatinine measurements were done
      in 24 patients 1-5 years after they recovered from PARF. RESULTS: Regardless of
      age, mean KBRs were significantly greater in patients than in healthy volunteers
      (< 65 years, p < 0.001; > or = 65 years, p = 0.008), with a negative correlation
      between KBR and patient age (r = -0.664; p < 0.001). A positive correlation was
      found between the KBR and the peak serum creatinine level in patients younger
      than 65 years (r = 0.543; p < 0.001); an insignificant negative correlation was
      found between these factors in patients 65 years or older (r = -0.264; p = 0.1).
      Follow-up on recovered patients showed that their KBRs were significantly lower
      than the values when patients had PARF (< 65 years, p < 0.001; > or = 65 years, p
      = 0.027). CONCLUSIONS: PARF produces a sonographically measurable increase in
      renal size.

PMID- 9608369
TI  - Epigastric pain and sonographic assessment of the pancreas in dengue hemorrhagic
      fever.
AB  - PURPOSE: This study reports the sonographic features of the pancreas in children
      who have dengue hemorrhagic fever (DHF) with epigastric pain, evaluates
      pancreatic abnormalities as the source of this pain, and relates sonographic
      findings, DHF status, and serum levels of amylase and lipase. METHODS: Over 3.5
      years, real-time sonographic examination of the pancreas was prospectively
      performed in 148 children (age range, 5 months-14 years) who had DHF with
      epigastric pain. The DHF diagnosis was confirmed by serologic examination and
      viral isolation. RESULTS: Of the 142 children included in this study, 72 had mild
      DHF (grade I or II) and 70 had severe DHF (grade III or IV). An enlarged pancreas
      was found in 41 patients (29%), 10 (14%) of whom had mild DHF and 31 (44%) of
      whom had severe DHF. The pancreas was hyperechoic relative to the liver in 36
      patients (25%), isoechoic in 98 (69%), and hypoechoic in 8 (6%). CONCLUSIONS: The
      majority of patients with DHF and epigastric pain do not have an enlarged
      pancreas, different echogenicity of the pancreas compared with the liver, or a
      dilated pancreatic duct. Thus, pathologic changes of the pancreas cannot be the
      only cause of epigastric pain in DHF patients. Increased serum levels of amylase
      and lipase are commonly seen in patients with severe DHF and an enlarged
      pancreas.

PMID- 9608370
TI  - Urethral complications of urinary catheterization presenting as primary scrotal
      masses: sonographic diagnosis.
AB  - We report on 2 debilitated male patients who had penile urethral complications of
      transurethral catheter drainage. One patient had a urethral diverticulum, and the
      other had a Foley catheter misplaced through a urethral perforation. Both lesions
      mimicked primary intrascrotal masses on physical examination and were therefore
      evaluated by scrotal sonography. The correct diagnosis of each lesion required
      careful examination of the mass and its anatomic relationship to the adjacent
      urethra. Penile urethral complications of catheterization in debilitated patients
      must be included in the differential diagnosis of scrotal cystic masses. These
      cases also emphasize the necessity of a thorough sonographic examination that
      extends beyond the specific area of presumed clinical interest.

PMID- 9608371
TI  - Carcinoma arising from ectopic pancreas in the stomach: endosonographic detection
      of malignant change.
AB  - We present a case of a submucosal tumor in the stomach that was suspicious for
      malignancy on preoperative endosonography. The resected tumor was histologically
      diagnosed as a ductal adenocarcinoma that originated in ectopic pancreatic tissue
      in the gastric wall. Although malignant transformation in ectopic pancreas is
      extremely rare, it remains an important consideration in the differential
      diagnosis of gastric submucosal masses.

PMID- 9608372
TI  - Preoperative sonographic diagnosis of sealed-off perforated gastric ulcer.
AB  - Perforated peptic ulcer (PPU) is a common surgical emergency. Early diagnosis and
      intervention are necessary to reduce the morbidity and mortality. Radiographic or
      sonographic detection of free air is neither sensitive nor specific for PPU. We
      report a case of sealed-off PPU with direct sonographic demonstration of the
      perforation tract within the anterior wall of the gastric antrum. The diagnosis
      was confirmed at laparotomy.

PMID- 9608373
TI  - Effervescent gallbladder: sonographic findings in emphysematous cholecystitis.
AB  - We report a case of emphysematous cholecystitis with the sonographic appearance
      of an "effervescent gallbladder"--a large amount of gas bubbles rising like
      bubbles in a glass of champagne from the dependent part of the gallbladder and
      floating to the nondependent part. The etiology of this finding was acute
      obstruction of the distal common bile duct by a stone and purulent cholangitis.
      Short-term follow-up sonography is important to confirm the diagnosis of
      cholecystitis.

PMID- 9608374
TI  - Prenatal sonographic appearance of congenital fibrosarcoma.
AB  - Congenital fibrosarcoma is a rare soft tissue sarcoma. A 22-year-old woman in the
      22nd week of her first pregnancy underwent sonographic examination, which
      revealed a soft tissue swelling of the fetus's left thigh. The pregnancy was
      terminated, and congenital fibrosarcoma was diagnosed by pathologic examination.
      To our knowledge, this is the first published report of the intrauterine
      sonographic observation of this tumor in a fetal extremity.

PMID- 9608375
TI  - Endometrial changes assessed by transvaginal sonography.

PMID- 9608376
TI  - A study of referral patterns among Queensland general medical practitioners to
      chiropractors, osteopaths, physiotherapists and others.
AB  - BACKGROUND: In Queensland, Australia, patients with work-related injuries must
      receive a referral from a general medical practitioner to receive treatment from
      such "nontraditional" practitioners as physiotherapists, chiropractors or
      osteopaths, even though these nontraditional practitioners are primary care
      providers outside of the workers' compensation system. The Chiropractors'
      Association of Australia (Queensland Branch) (CAAQ) believed that injured workers
      wishing to receive chiropractic care stood little chance of obtaining a medical
      referral. On the other hand, the General Manager of the Workers' Compensation
      Board of Queensland maintained that injured workers had little difficulty
      obtaining such a referral for chiropractic care. OBJECTIVE: To canvass general
      medical practitioner attitudes and referral patterns to chiropractors,
      osteopaths, physiotherapists and other nontraditional practitioners
      (naturopaths). DESIGN: A descriptive study in which 1509 general medical
      practitioners in private practice in Queensland were invited to respond to a
      mailed questionnaire. The sample represented 50% of all such practitioners in
      Queensland. RESULTS: A 52% response rate was obtained with 784 (638 male, 142
      female general practitioners) questionnaires returned. Respondents' ages ranged
      from 27 to 79 yr. The respondents' years in practice ranged from 1 to 55 yr. The
      survey showed that attitudes and referral patterns were distinctly different
      depending on the nontraditional practitioner group in question. CONCLUSION: The
      survey results confirm that general medical practitioners are highly unlikely to
      have professional dealings with chiropractors and osteopaths, including referral
      of patients to said providers, even if the patient requests such a referral, and
      that general medical practitioners are much more likely to have professional
      dealings with physiotherapists than with any of the other nontraditional groups
      considered.

PMID- 9608377
TI  - Evaluation of orthopedic testing of the low back for nonspecific lower back pain.
AB  - OBJECTIVE: To assess the value of some commonly used orthopedic tests used in
      evaluating nonspecific lower back pain where there are no demonstrable
      pathological or neurological deficits. DESIGN: Retrospective analysis of patient
      files. SETTING: Chiropractic teaching clinic, Royal Melbourne Institute of
      Technology. SUBJECTS: Five hundred sixty-four files of patients presenting to the
      above clinic with nonspecific lower back pain were analyzed. DATA ANALYSIS: The
      data were entered into a spreadsheet, contingency tables were created, and the
      data were analyzed using chi 2 tests. Statistical significance was set at p <
      .05. RESULTS: Kemp's and Yeoman's tests were most commonly positive, whereas
      Bonnet's, supported Adams' and axial compression tests showed relatively low
      positive results. The factors studied that affected the rate of positive
      responses were age, gender, pain site, duration and cause. The number of previous
      episodes of lower back pain had no effect on the positive test rates. CONCLUSION:
      For cases of nonspecific, mechanical lower back pain, orthopedic testing has
      limited clinical value once nerve root problems and pathologies have been ruled
      out. Kemp's and Yeoman's tests were the most frequently positive, and seemed to
      be the most useful in diagnosing nonspecific lower back pain. When selecting the
      most appropriate tests to use, one needs to take into account the patient profile
      and history.

PMID- 9608378
TI  - Neck support pillows: a comparative study.
AB  - BACKGROUND: Special neck support pillows claiming to improve rest and reduce neck
      pain are currently being advertised. OBJECTIVE: To test whether neck pillows have
      any positive effect on neck pain and quality of sleep compared with usual pillows
      and, if so, to find the optimal characteristics of such a pillow. METHODS: Thirty
      seven hospital employees and 18 neck patients were asked to test six neck pillows
      with different shapes and consistency randomly over the course of 3 wk, to grade
      them according to comfort and to describe the characteristics of an ideal pillow.
      RESULTS: Thirty-six of 55 persons found the pillows positively affected sleep and
      27 of 42 found that they positively affected neck pain. The ideal pillow should
      be soft and not too high, should provide neck support and should be allergy
      tested and washable. The pillow that included two firmer supporting cores for
      neck lordosis received the best rating. CONCLUSION: A neck pillow with good shape
      and consistency and with firm support for cervical lordosis can be recommended as
      a part of treatment for neck pain.

PMID- 9608379
TI  - A cervical manikin procedure for chiropractic skills development.
AB  - OBJECTIVE: To determine whether chiropractic students can effectively acquire
      adjustive skills for the cervical spine by utilizing a Thrust in Motion Cervical
      (TMC) manikin and to evaluate its value as a teaching aid. A pilot study was
      formulated and incorporated into the skills tutorial program at Macquarie
      University. Centre for Chiropractic in Sydney, Australia. DESIGN AND SETTING: A
      prospective study was performed on chiropractic students with no prior experience
      in performing spinal adjustments. SUBJECTS: Twenty subjects were selected
      randomly from a population of 75 students about to commence their 4th-yr Master's
      of Chiropractic program. INTERVENTION: Students who formed the experimental group
      (n = 6) did not perform any thrusting maneuvers on human subjects while
      practicing Diversified chiropractic cervical spinal techniques. They practiced
      the adjustive thrust only on the TMC manikin. The control group (n = 14) learned
      in the established "hands-on" approach, performing thrusting maneuvers on fellow
      student subjects. Both groups were supervised, taught and examined in an
      otherwise identical fashion. RESULTS: The data indicate there is no significant
      difference between the examination scores of the student group that practiced on
      the TMC manikin (average, 2.17 points) compared with the controls (2.13 points),
      with a confidence interval at p = .985, assuming that 0.5 marks is clinically
      important in these examination results. Interexam reliability was acceptable
      (Pearson's r = .73) for both experimental and control examination performances.
      CONCLUSION: The null hypothesis is accepted, and no significant difference in
      student examination performance was found between those who learned thrusting on
      the manikin alone and those who learned on fellow students. Further, for the
      first time, a manikin has been shown to be effective in teaching chiropractic
      skills. The implications of the TMC manikin procedure will revolutionize the
      acquisition of motor learning skills that are essential for chiropractic skills
      training.

PMID- 9608380
TI  - Exposure margin in skeletal radiography and its effect on tube tilt compensation.
AB  - OBJECTIVE: To examine the rationale for and necessity of adjusting the film focal
      distance when X-ray angulation is employed during a radiographic study, and to
      determine the sensitivity of human interpreters to overall differences in film
      density and the correlation, if any, with digital analysis of radiographic films.
      DESIGN AND SETTING: The study was performed in the radiology department at Logan
      College of Chiropractic in St. Louis, Missouri. A standard X-ray phantom of the
      hand and wrist and several aluminum step wedges were exposed from 10% to 250% of
      baseline exposure intensity using equipment commonly found in a field doctor's
      practice. EVALUATION: The films were independently rated for overall image
      quality on a visual analog scale by five board-certified chiropractice
      radiologists. The films were also digitized, and selected regions analyzed on a
      computer. RESULTS: The panel of radiologists was able to consistently grade
      exposure intensity differences of approximately 10% relative change between
      films. The perceived density was directly proportional to the logarithm of the
      exposure intensity, as would be predicted from theoretical film response
      characteristics. The range of "acceptable" image quality was determined to lie
      between -40% and +60% of the baseline technique. CONCLUSIONS: This study
      validated the empirically derived tube tilt correction factor of 1 in of vertical
      adjustment per 5 degrees of tube angulation for tube tilts greater than or equal
      to 20 degrees. Underexposure impaired the interpretation of radiographs more than
      overexposure. Experienced human observers were able to reliably discriminate
      exposure differences on the order of 10% relative change when presented with
      complex grey-scale images, such as plain film radiographs.

PMID- 9608381
TI  - Reliability of spinal displacement analysis of plain X-rays: a review of commonly
      accepted facts and fallacies with implications for chiropractic education and
      technique.
AB  - BACKGROUND: Current medical, biomechanical, and chiropractic literature indicates
      that X-ray line drawing analysis for spinal displacement is reliable, with high
      Interclass Correlation Coefficients (ICCs) found in most studies. Normal sagittal
      spinal curvatures are being accepted as important clinical outcomes of care;
      however, just the opposite is taught in many chiropractic college radiology
      courses. OBJECTIVE: To review the current literature on X-ray line drawing
      reliability and abnormal static lateral positions. DATA SOURCES: Searches were
      performed on Medline, Chiro-LARS, MANTIS, and CINAHL on X-ray reliability, normal
      spinal position, and sagittal spinal curvatures as clinical outcomes. RESULTS: X
      ray line drawing analysis for spinal displacement was found to have high
      reliability with a majority of ICCs in the .8-.9 range. The reliability for
      determining X-ray pathology was found to be only fair to good by both medical
      doctors and chiropractors and by both chiropractic and medical radiologists, with
      a majority of ICCs in the range .40-.75. Muscle spasms, facet hyperplasia, short
      pedicles and patient positioning errors have not been shown to alter sagittal
      plane alignment. The sagittal spinal curves are desirable clinical outcomes of
      care in surgery, physical therapy, rehabilitation and chiropractic. These results
      contradict common claims found in the indexed literature. CONCLUSION: X-ray line
      drawing is reliable. Normal values for the sagittal spinal curvatures exist in
      the literature. The normal sagittal spinal curvatures are important clinical
      outcomes of care. Patient positioning and postural radiographs are highly
      reproducible. When these standardized procedures are used, the pre-to-post
      alignment changes are a result of treatment procedures applied. Chiropractic
      radiology education and publications should reflect the recent literature,
      provide more support for X-ray line drawing analyses and applications of line
      drawing analyses for measuring spinal displacement on plain radiographs.

PMID- 9608382
TI  - Dysafferentation: a novel term to describe the neuropathophysiological effects of
      joint complex dysfunction. A look at likely mechanisms of symptom generation.
AB  - BACKGROUND AND OBJECTIVES: Since the founding of the chiropractic profession,
      very few efforts have been made to thoroughly explain the mechanism(s) by which
      joint complex dysfunction generates symptoms. Save for a few papers, only vague
      and physiologically inconsistent descriptions have been offered. The purpose of
      this article is to propose a precise and physiologically sound mechanism by which
      symptoms may be generated by joint complex dysfunction. DATA SOURCES: The data
      was accumulated over a period of years by reviewing contemporary articles and
      books, and subsequently retrieving relevant papers. Articles were also selected
      from volumes 1-4 of the Chiropractic Research Archives Collection. The Nexus,
      published by the David D. Palmer Health Sciences Library, and In Touch, published
      by Logan College of Chiropractic Library, were reviewed and relevant articles
      were retrieved. Medline searches were found to be ineffective because appropriate
      key indexing terms were difficult to identify. DATA SYNTHESIS: The symptoms
      generated by joint complex dysfunction, such as pain, nausea and vertigo, are
      probably caused by increased nociceptive input and/or reduced mechanoreceptive
      input. CONCLUSIONS: Joint complex dysfunction should be included in the
      differential diagnosis of pain and visceral symptoms because joint complex
      dysfunction can often generate symptoms which are similar to those produced by
      true visceral disease.

PMID- 9608383
TI  - Posterior limbus fractures: five case reports and a review of selected published
      cases.
AB  - OBJECTIVE: To discuss the clinical presentation of posterior limbus fractures and
      present a review of the literature on this topic. CLINICAL FEATURES: Patients
      presented with a combination of lower back pain, muscle spasm, diminished reflex
      responses, restricted motion and foot drop. In some cases, onset followed trauma;
      in others, it did not. INTERVENTION AND OUTCOME: Some patients required surgical
      intervention, whereas others underwent chiropractic manipulation and other
      conservative interventions. CONCLUSION: Posterior limbus fractures represent an
      avulsion of the ring apophysis from the vertebral body. Appropriate diagnostic
      work-up can help determine the presence of this condition. Management
      considerations are discussed.

PMID- 9608384
TI  - Manipulative therapy in lower back pain with leg pain and neurological deficit.
AB  - OBJECTIVE: To discuss a case of sciatica associated with lower back pain that
      originates in a disc. We discuss the use of manipulative therapy as a
      conservative approach and compare it with other conservative methods and with
      surgery. CLINICAL FEATURES: The patient suffered from lower back and left leg
      pain that had increased in severity over a 6-day period. There was decreased
      sensation in the dorsum of the left foot and toes. Computed tomography
      demonstrated the presence of a small, contained disc herniation. INTERVENTION AND
      OUTCOME: The patient was initially treated with ice followed by flexion
      distraction therapy. This was used over the course of her first three visits.
      Once she was in less pain, side posture manipulation was added to her care. Nine
      treatments were required before she was released from care. CONCLUSION: We need a
      nonsurgical, conservative approach to treat lower back pain with sciatica as an
      alternative to and before beginning the more aggressive, and potentially
      hazardous, surgical treatment. There is some support for the idea that lumbar
      disc herniation with neurological deficit and radicular pain does not
      contraindicate the judicious use of manipulation. Although significant questions
      remain for the evaluation and treatment of lumbar radiculopathy (sciatica) with
      disc herniations, there is ample evidence to suggest that a course of
      conservative care, including spinal manipulation, should be completed before
      surgical consult is considered.

PMID- 9608385
TI  - Changes in brain function after manipulation of the cervical spine.

PMID- 9608386
TI  - Changes in brain function after manipulation of the cervical spine.

PMID- 9608387
TI  - Changes in brain function after manipulation of the cervical spine.

PMID- 9608388
TI  - Changes in brain function after manipulation of the cervical spine.

PMID- 9608389
TI  - Changes in brain function after manipulation of the cervical spine.

PMID- 9608390
TI  - How real is the subluxation?

PMID- 9608391
TI  - The effectiveness of chiropractic management of fibromyalgia patients.

PMID- 9608392
TI  - Influence of processing variables on the properties of gelatin microspheres
      prepared by the emulsification solvent extraction technique.
AB  - The influence of the process parameters on the particle size and
      microencapsulation efficiency of gelatin microspheres prepared by the
      emulsification solvent extraction technique was investigated. The processing
      parameters studied were time and speed of emulsification, gelatin concentration
      and the presence of a surfactant and its concentration. Increasing duration of
      emulsification > 5 min, and surfactant concentration < or = 1% (w/w)
      significantly reduced the particle size of the microspheres. Emulsification speed
      did not influence the particle size significantly. A large increase in particle
      size was obtained with gelatin concentrations > 20% (w/v). Using riboflavin as a
      model drug, gelatin products differing in Bloom value were tested for a possible
      dependence of degree of microencapsulation and particle size on the viscosity of
      the gelatin used. Both degree of microencapsulation (84.2-96.0%) and mean
      particle size (22.1-32.0 microns) were found to be independent of the viscosity
      grade used.

PMID- 9608393
TI  - Effect of emulsifier blend on the characteristics of sustained release diclofenac
      microspheres.
AB  - This investigation involved the evaluation of the emulsifier blend effect on the
      development of sustained release diclofenac microspheres intended for use in a
      suspension formulation. The microspheres were prepared using the hydrophobic
      congealable disperse phase method. The emulsifier blend consisted of glycerol,
      monostearate (GMS), a hydrophobic emulsifier with HLB = 3.8, and Tween 80, a
      hydrophilic emulsifier with a HLB value of 15. The effect of this blend on the
      encapsulation efficiency, size distribution and drug release from the
      microspheres was studied. A critical amount of GMS (> 0.2 g) was found to be
      necessary for good encapsulation efficiency. X-ray diffractograms revealed that
      the drug retains its crystalline state within the microspheres, indicating that
      the drug is present as a dispersion within the wax matrix. Increasing amounts of
      Tween 80 caused an increase in the drug release while increased amounts of GMS
      retarded the release. The hydrophilic emulsifier and the emulsifier blend
      influenced the size distribution of the formed microspheres. With an increase in
      the amount of hydrophilic emulsifier, there was an initial increase in the
      percent of desired size fraction (137.5 microns) of microspheres followed by a
      decrease. Microspheres with a larger size released the drug slowly compared to
      smaller size microspheres, while increase in drug load increased the rate of drug
      release. The release pattern fitted the Higuchi dissolution kinetics for
      spherical matrices. Different impeller blade designs formed microspheres that
      exhibited different release rates. The microspheres (mean size 137.5 microns),
      had a release profile that made them suitable to be formulated as a sustained
      release suspension.

PMID- 9608394
TI  - New strategies for the microencapsulation of tetanus vaccine.
AB  - The progress toward the development of a single dose tetanus vaccine has been
      limited by the poor stability of the protein antigen, tetanus toxoid (TT), during
      its encapsulation in, and release from, biodegradable polymer microspheres. To
      investigate alternative microencapsulation approaches that may improve the
      stability of TT under these conditions, a two-step microencapsulation method has
      been devised to form microcapsules which consist of: (a) forming microcores of TT
      in a hydrophilic support matrix by spray-congealing, followed by (b) coating the
      microcores with poly(lactide-co-glycolide) (PLGA) by an oil-in-oil solvent
      extraction method. Several protein stabilizers including gelatin (with or without
      poloxamer 188), dextran, sodium glutamate, and polyethylene glycol were examined
      as potential core-materials. Among them, gelatin was superior in its ability to
      impart stability to TT against heat and moisture-induced inactivation. Microcores
      of this latter stabilizer and TT were encapsulated in PLGA using the foregoing
      technique, which exposed the dry antigen to minimal water in order to prevent its
      irreversible inactivation during exposure to the organic solvent. The
      microencapsulation method resulted in minimal loss of antigenically active TT
      (approximately 10-20%). Microscopic analysis of the microcapsules following
      preparation showed the microcores to be fully encapsulated. However,
      microcapsules containing TT and gelatin released the active antigen nearly
      completely within one day. Fluorescence confocal microscopy revealed that the
      swelling of the hydrophilic core-material was responsible for the burst-release
      behaviour. Manipulation of the polymer coating could not slow down this
      'explosion' of the microcapsules. TT-containing PLGA microcapsules have been
      prepared using a novel microencapsulation method, which retains an extremely high
      fraction of antigenically active TT. Hence, these mechanistic approaches may be
      useful in the development of effective single-dose vaccines.

PMID- 9608395
TI  - Effect of magnesium stearate on chitosan microspheres prepared by an
      emulsification-coacervation technique.
AB  - Chitosan microspheres were prepared using an emulsification-coacervation
      technique. The w/o emulsion comprised a mixture of light and heavy liquid
      paraffins containing sodium dioctyl sulphosuccinate as the oil phase and chitosan
      solution as the aqueous phase. Pentasodium tripolyphosphate was included as a
      counterion. The chitosan microspheres obtained showed a high degree of
      aggregation. This was markedly reduced, by the incorporation of magnesium
      stearate in the disperse phase. The resultant microspheres were then discrete,
      spherical with smooth surfaces. Additionally, with an increasing magnesium
      stearate content, larger-sized microspheres were produced. The DSC analysis data
      suggested that the magnesium stearate was converted to stearic acid during the
      preparation process. Chitosan microspheres containing propranolol hydrochloride
      were similarly prepared, but their surface was convoluted and their shape not
      well defined. Unlike the microspheres without drug, the size of the drug-loaded
      microspheres decreased with increasing magnesium stearate content. The release of
      propranolol hydrochloride from the microspheres was fast, irrespective of the
      content of magnesium stearate. Drug encapsulation efficiency was enhanced when a
      greater amount of magnesium stearate was used.

PMID- 9608396
TI  - Microencapsulation of the renin inhibitor FK906 by phase separation of
      ethylcellulose in cyclohexane.
AB  - Microencapsulation of the renin inhibitor FK906 (tripeptide) by phase separation
      of ethylcellulose in cyclohexane was performed to obtain sustained release of the
      drug for a once-a-day application. Owing to the binding characteristics and to
      the very low solubility of FK906 in cyclohexane, microencapsulation can be
      performed after granulation of the drug with an inert filler, and no additional
      binder is required. Microcapsules with a particle size of 180-590 microns are
      obtained in a yield of 70%. Drug content determinations and SEM-micrographs
      reveal the almost complete incorporation of the polymer for the coating and the
      high quality of the microcapsule wall. Despite the strongly pH-dependent
      solubility of FK906 (.HCl) in water, the microcapsules show almost identical
      sustained-release curves at pH 1.2 and 6.0 (0.05 M phosphate buffer). This is
      explained by an acidic microenvironment inside the microcapsules at both pHs
      investigated and was attributed to the intrinsic physico-chemical properties of
      FK906 which help to overcome the buffer capacity of the phosphate buffer, pH 6.0,
      inside the microcapsules. This theory was confirmed by solubility experiments at
      pH 6.0 using excess amounts of FK906 as well as by dissolution tests as a
      function of the buffer capacity and the osmolality of the dissolution medium. The
      buffer capacity was found to be the parameter with greater influence on the
      release rate.

PMID- 9608397
TI  - Vitamin E improves the uptake of unsaturated soya lecithin liposomes by human
      fibroblasts in vitro.
AB  - Liposomes may exert certain toxic effects on human cells depending on their
      composition and concentration when used as drug carriers. In this study, the
      behaviour of human fibroblasts in the presence of soya phosphatidylcholine (soya
      PC) liposomes and the effect of the incorporation of vitamin E into the membrane
      of such liposomes, was investigated. Human fibroblasts were incubated for 72 h
      with low (50 microM) and high (200 microM) concentrations of large, unilamellar
      (LUV) soya-PC liposomes in the presence and absence of vitamin E (soya-PC:vitamin
      E; 10:0.5). The resulting cultures were studied by scanning and transmission
      electron microscopy, fluorescence microscopy and labelling with rhodamine B. The
      large unilamellar soya-PC liposomes obtained were of mean diameter 86.4 nm (soya
      PC) and 78.3 nm (soya-PC: vitamin E). No significant changes in cell viability
      were observed between untreated fibroblasts and those incubated with 50 microM
      soya-PC liposomes. In contrast, a marked loss of cells was apparent at a
      concentration of 200 microM soya-PC liposomes which was reversible by the
      addition of vitamin E. Morphological changes including the production of
      microvilli or 'bubbling' of the cell membrane, were incurred by some of the
      fibroblasts on addition of soya-PC liposomes. The addition of vitamin E did not
      affect the changes produced at the lower liposome concentrations but was able to
      reduce the cytotoxic effects occurring at higher concentrations, possibly by
      inhibiting the formation of liposome aggregates. The use of PC-soya liposomes
      containing vitamin E at high concentrations is proposed as a means of delivering
      high doses of drugs.

PMID- 9608398
TI  - Influence of the preparation methods on the drug release behaviour of loperamide
      loaded nanoparticles.
AB  - Polylactide (PLA) or poly(lactide-coglycolide) (PLGA) nanoparticles containing
      loperamide (LPM) were prepared by an incorporation or adsorption method with the
      objective of developing nanoparticles with a rapid drug release. The use of
      polymers such as PLA with lower molecular weights and the addition of sorbitan
      fatty acid esters (SFAE) for the incorporation led to an almost complete
      entrapment of LPM in nanoparticles. Preparation of PLA nanoparticles by
      adsorption was performed by addition of LPM methanol solution before, during and
      after evaporation of dichloromethane from the system. The adsorption of LPM onto
      the nanoparticles with low molecular weight PLA (m.w. 2000) showed an isotherm
      with a good correlation to the Langmuir equation. A high amount of LPM can be
      entrapped or adsorbed in nanoparticles only with low molecular weights of PLA or
      PLGA. In the incorporation method, the addition of SFAEs increased drug
      entrapment. However, in the adsorption method they had no effect on nanoparticle
      drug adsorption. The drug-release profiles from both nanoparticles, prepared by
      the adsorption and incorporation methods, were biphasic with an initial rapid
      release and a second slower release phase, although their initial extents of
      release were different. The release rates were almost the same for both the
      adsorption and incorporation method without SFAEs. The addition of SFAEs to the
      adsorption system increased the extent of drug release from nanoparticles. In
      conclusion, a rapid loperamide release from nanoparticles can be achieved by use
      of PLA or PLGA with low molecular weights and in the adsorption method by the
      addition of SFAEs.

PMID- 9608399
TI  - Preparation and evaluation of sustained release cross-linked chitosan
      microspheres containing phenobarbitone.
AB  - Chitosan microspheres containing phenobarbitone were successfully prepared by
      glutaraldehyde cross-linking of an aqueous acetic acid dispersion of chitosan in
      light liquid paraffin containing sorbitan mono-oleate as a stabilizing agent.
      Uniform and spherical microspheres, with a loading efficiency up to 57.2%, could
      be prepared depending on the preparation conditions. The main parameters
      affecting the preparation and the performance of the prepared microspheres were
      the molecular weight and concentration of chitosan as well as the concentration
      of the used stabilizing agent. The incorporation of citric acid into the
      microspheres was found to increase the formation of a water-soluble gel when the
      microspheres come in contact with the dissolution medium increasing the rate of
      drug release. The particle size was shifted towards smaller diameters with
      increased concentration of sorbitan mono-oleate, up to 4.0% v/v, by use of a
      lower concentration of chitosan (1.0% w/v) and chitosan with low molecular
      weight. Rapid initial drug release (20-30% of the incorporated drug) was
      exhibited in all the prepared microspheres followed by slow release of the
      remaining amount of the drug. The release rate of the drug from the microspheres
      prepared from high molecular weight chitosan was slow in comparison with that
      prepared from medium and low molecular weight chitosan. High concentrations of
      sorbitan mono-oleate increased the rate of drug release.

PMID- 9608400
TI  - Functionality of protective colloids affecting the formation, size uniformity and
      morphology of drug-free polylactic acid microspheres.
AB  - Drug-free polylactic acid (PLA) microspheres were prepared by an emulsification
      solvent evaporation technique using different types of protective colloids. The
      influence of five types of hydrophilic prolymers (polysaccharides, proteins,
      synthetic cellulose derivatives, synthetic nonionic polymers and surfactants) on
      the formation, size uniformity and morphology of PLA microspheres was
      investigated. Four characteristic functions (surface activity, viscosity,
      electric charge and interfacial film formation) of the hydrophilic polymer
      aqueous solutions were used to evaluate the efficacy of these protective colloids
      used. The results indicate that these four functions were the key parameters to
      achieve the formation of PLA microspheres. The best protective colloid should
      have high surface activity, optimum viscosity, adequate electric charge, and form
      an interfacial film to give a higher recovery, better size uniformity and
      smoother topography of the PLA microspheres.

PMID- 9608401
TI  - Mild cognitive impairment and risk of mortality in HIV-1 infection.
AB  - HIV-1-associated cognitive impairment has only been preliminarily investigated
      for associations with mortality. The authors examined 119 HIV-1-positive
      homosexual men (asymptomatic: n = 96; early symptomatic: n = 23). At follow-up
      (to 3.5 years), there were 105 survivors and 14 nonsurvivors. Those at the 25th
      percentile in response speeds and in long-term memory retrieval accuracy were at
      6.4 (P < 0.02) and 3.5 (P < 0.05) times increased mortality risk, respectively,
      of those at the 75th percentile--independent of baseline CDC clinical stage, CD4
      cell count, hemoglobin level, antiretroviral and prophylactic medication use, and
      sociodemographics. Cognitive impairment should be identified early--for
      maximization of both functional status and survival time.

PMID- 9608402
TI  - Magnetic resonance spectroscopy in affective disorders.
AB  - Magnetic resonance spectroscopy (MRS) is a non-invasive tool for in vivo chemical
      analysis that has been applied to neurobiological or psychopharmacological
      studies of affective disorders. Studies employing 31P-MRS and 1H-MRS have
      indicated possible abnormalities in membrane phospholipid metabolism, high-energy
      phosphate metabolism, and intracellular pH in affective disorders. They have also
      suggested that lithium increases the phosphomonoester (possibly inositol-1
      phosphate) peak in the brain but does not increase that of choline-containing
      compounds in the brain. Studies employing 7Li-MRS and 19F-MRS have elucidated the
      pharmacokinetic properties of lithium, fluoxetine, and fluvoxamine in the brain
      in patients treated with these drugs.

PMID- 9608403
TI  - Selective pharmacological activation of limbic structures in human volunteers: a
      positron emission tomography study.
AB  - Using a pharmacological probe, procaine hydrochloride, the authors elicited
      consistent and selective activation of anterior limbic and paralimbic structures
      in normal human volunteers as documented by H215O positron emission tomography.
      This activation was associated with a range of emotional, somatic, and visceral
      experiences, often similar to those experienced during the aura of temporal lobe
      epilepsy. Several subjects also experienced panic attacks. This study confirms
      that selective anterior limbic/paralimbic activity in normal human volunteers
      evokes many emotional phenomena as well as common "ill-defined" symptoms observed
      in clinical conditions. The present combination of procaine challenge and
      neuroimaging provides a noninvasive procedure to probe the contribution of
      different anterior limbic and paralimbic structures to normal human emotions and
      to neuropsychiatric disorders.

PMID- 9608404
TI  - Frontal systems dysfunction in children with attention-deficit/hyperactivity
      disorder and learning disabilities.
AB  - Tests of attention, inhibition, working memory, motor learning, and problem
      solving--functions associated with the brain's frontal systems--were administered
      to 26 children with attention-deficit/hyperactivity disorder and learning
      disabilities (ADHD + LD), 22 children with LD only, and 10 with ADHD only.
      Percentages of abnormal test results and significantly impaired scores were
      higher for the two groups with LD than for the ADHD-only group. The groups
      differed significantly on some tests of attention-inhibition-cueing, working
      memory, and problem solving, with the ADHD + LD and LD groups performing worse
      than the ADHD-only group. Abnormalities of frontal systems tests are not
      exclusive ADHD characteristics and are also present in LD children, implying a
      strong connection between centers of "processing" and centers of "executive"
      functions.

PMID- 9608405
TI  - Age-related changes in brain glucose metabolism in adults with attention
      deficit/hyperactivity disorder and control subjects.
AB  - Using positron emission tomography and [18F]-2-fluoro-2-deoxy-D-glucose, the
      authors determined cerebral metabolic rates for glucose (CMRglc) in 39 adults (18
      51 years old) with attention-deficit/hyperactivity disorder (ADHD) and 56 healthy
      control adults (19-56 years old) during the performance of a continuous attention
      task. Increased age was associated with reduced global CMRglc in ADHD women, but
      not in ADHD men, control men, or control women. Better performance on the
      attention task was significantly associated with increased age only in the ADHD
      female group. Determining the role of behavioral, hormonal, and genetic factors
      is a challenge for future research.

PMID- 9608406
TI  - Changes in seizure threshold over the course of electroconvulsive therapy affect
      therapeutic response and are detected by ictal EEG ratings.
AB  - Therapeutic effectiveness of electroconvulsive therapy is influenced by the
      degree to which the stimulus intensity exceeds the seizure threshold. However,
      the threshold rises variably over the treatment course, confounding maintenance
      of desired relative stimulus intensity. In 47 depressed patients, decreases in
      relative stimulus intensity between treatments 1 and 6 were associated with
      diminished therapeutic response at treatment 6 for unilateral (UL) ECT. A
      multivariate model including manual ratings of ictal EEG data predicted whether
      seizure threshold rose with 82% accuracy. The same EEG variables were also
      significantly related to therapeutic response. Thus, decreases in relative
      stimulus intensity over the ECT course affect the therapeutic potency of UL ECT.
      Further, ictal EEG indices have considerable potential for predicting such
      stimulus intensity changes and their effect on therapeutic outcome.

PMID- 9608407
TI  - Effectiveness of ECT in patients with parkinsonism.
AB  - Electroconvulsive therapy (ECT) has been used to treat the psychiatric
      complications of Parkinson's disease. Concurrent improvement of parkinsonian
      motor symptoms has been noted. This retrospective study compared the outcomes of
      25 patients with parkinsonism receiving ECT for psychiatric indications with
      outcomes of 25 patients (matched for age and gender) without neurological disease
      also receiving ECT for psychiatric indications. Significant improvement in
      psychiatric symptoms was noted following ECT for both groups. No differences in
      efficacy of ECT were found between the two groups. Fourteen of the 25 patients
      with Parkinson's symptoms were noted to have at least transient improvement in
      motor function at discharge. ECT is an effective treatment for patients with
      parkinsonism and psychiatric comorbidity.

PMID- 9608408
TI  - Delusional misidentification in association with parkinsonism.
AB  - The delusional misidentification syndrome (DMS) has been associated with a range
      of neurological conditions. Three cases of DMS in patients with Parkinson's
      disease and dementia, treated with dopaminergic medications, are presented. It is
      postulated that DMS associated with parkinsonism results from a combination of
      dopaminergic psychosis and cognitive dysfunction involving the frontal lobe in
      particular. DMS in the setting of parkinsonism may be more frequent than commonly
      supposed.

PMID- 9608409
TI  - Is delirium different when it occurs in dementia? A study using the delirium
      rating scale.
AB  - The authors studied 61 geropsychiatric patients with delirium from a cohort of
      843 consecutive admissions to a geriatric clinical research unit. A central study
      goal was to assess how the presence of dementia affected the presentation of
      delirium. Eighteen delirious (D) and 43 delirious-demented (D-D) patients were
      compared on the Delirium Rating Scale (DRS), Mini-Mental State Examination
      (MMSE), Brief Psychiatric Rating Scale (BPRS), and EEG. D-D patients had lower
      MMSE scores, but no differences were found in total DRS or BPRS scores or in EEG
      grade. DRS items were similar in the two groups except that D-D had more
      cognitive impairment than D. An exploratory principal components analysis of DRS
      items identified two core factors. The authors conclude that the presentation of
      delirium in the setting of concurrent dementia is very similar to delirium
      without dementia, with subtle differences probably attributable to dementia.

PMID- 9608410
TI  - Cognitive decline in patients on an acute geropsychiatric unit.
AB  - The authors compared patients in a geropsychiatric unit who showed marked
      cognitive decline during hospitalization with those who did not. Patients who
      declined in cognitive function were older, were more likely to have a diagnosis
      of dementia, and were more anergic on admission. These patients were also
      discharged to more restrictive living environments. The subgroup of demented
      patients who declined in cognitive function were also older and improved less on
      anxiety and depression.

PMID- 9608411
TI  - Subtle neurological deficits and psychopathological findings in substance-abusing
      homeless and non-homeless veterans.
AB  - This study evaluated the hypothesis that homeless individuals would display
      higher levels of neurological deficits than non-homeless individuals,
      particularly in frontal lobe or executive functions. Eighteen acutely homeless,
      15 chronically homeless, and 20 non-homeless individuals admitted to an inpatient
      psychiatric service received a battery of neurological and psychosocial measures.
      In comparison to non-homeless subjects with comparable levels of psychopathology,
      homeless individuals showed higher levels of hostility, prior criminal activity,
      and family history of psychiatric illness, but lower levels of depression. A
      positive relationship between hostility and neurological soft signs was observed
      among chronically homeless subjects. These results suggest that a substantial
      subset of nonpsychotic homeless veterans suffers from "occult" neurological
      deficits.

PMID- 9608412
TI  - Quetiapine (Seroquel) in the treatment of psychosis in patients with Parkinson's
      disease.
AB  - Psychoses are a common clinical problem in patients with Parkinson's disease.
      Treatment with typical neuroleptics or withdrawal of antiparkinsonian drugs may
      improve mental symptoms but will worsen the parkinsonism. Quetiapine (Seroquel),
      ICI 204,636, is a novel antipsychotic medication with a low potential for
      producing extrapyramidal side effects. In this open-label clinical study of 2
      patients with Parkinson's disease, treatment with Seroquel successfully
      controlled psychotic symptoms without worsening of motor disability.

PMID- 9608413
TI  - Risperidone for the treatment of behavioral disturbances in dementia: a case
      series.
AB  - The authors describe a series of 22 patients with dementia and behavioral
      disturbances, including agitation, aggression, delusions, and hallucinations, who
      were treated with risperidone. Risperidone, in low doses, was well tolerated; 50%
      of patients experienced significant improvement, although 50% experienced some
      extrapyramidal symptoms.

PMID- 9608414
TI  - A preliminary study of D-cycloserine treatment in Alzheimer's disease.
AB  - D-cycloserine is a partial agonist on the glycine site of the N-methyl-D
      aspartate glutamate receptor. This double-blind crossover study of 15 mg D
      cycloserine in Alzheimer's disease patients did not demonstrate clinical benefit.
      Higher medication dosage or long-term treatment may be required.

PMID- 9608415
TI  - Neuroleptic sensitivity to clozapine in dementia with Lewy bodies.
AB  - Dementia with Lewy bodies (DLB) may be one of the most common causes of dementia.
      It should be of particular interest to psychiatrists because hallucinations are
      common presenting symptoms and because patients with DLB may be particularly
      sensitive to neuroleptics with respect to developing extrapyramidal symptoms. The
      authors describe 2 patients with DLB who were intolerant of clozapine, showing
      not extrapyramidal side effects, but an increase in confusion and behavioral
      symptoms.

PMID- 9608417
TI  - Treatment of a case of comorbid bipolar disorder and attention
      deficit/hyperactivity disorder.

PMID- 9608418
TI  - Acute psychosis associated with butorphanol.

PMID- 9608419
TI  - Organic catatonia following frontal lobe injury: response to clozapine.

PMID- 9608420
TI  - Enantioselective immunoaffinity extraction for simultaneous determination of
      optically active bufuralol and its metabolites in human plasma by HPLC.
AB  - A combined method of immunoaffinity extraction with high-performance liquid
      chromatography has been developed for the enantioselective determination of
      bufuralol and its metabolites in human plasma. The antibodies having high
      affinity toward the asymmetric center at the C-1 position of bufuralol and its 1'
      oxidized metabolites and low affinity to their antipodes were elicited by
      immunization of rabbits with immunogens, (1R)- and (1S)-1'-oxobufuralol O
      carboxymethyloxime-bovine serum albumin conjugates, respectively. 0.5 ml Of the
      immunoaffinity adsorbent (7.6 mg.ml-1 for anti-(1S)-antibody and 28.8 mg.ml-1 for
      anti-(1R)-antibody) prepared by immobilization of an antibody was capable of
      retaining up to 1 microgram of (R)- and (S)-bufuralol and up to 500 ng of other
      metabolites. The adsorbates were recovered quantitatively by elution with
      methanol-10 mM ammonium acetate buffer (pH 5) (95:5, v/v) without any interfering
      peaks on the high-performance liquid chromatogram. The proposed method was
      evaluated to be useful for the simultaneous determination of optically active
      bufuralol and its metabolite in plasma with acceptable recovery and precision.

PMID- 9608421
TI  - In vitro toxicity of N3-methyl-5'-deoxy-5-fluorouridine, a novel metabolite of
      doxifluridine: a bioanalytical investigation.
AB  - The cytotoxicity of N3-methyl-5'-deoxy-5-fluorouridine (N3-Me-5'-dFUR), a novel
      metabolite of the anticancer pro-drug 5'-deoxy-5-fluorouridine (5'-dFUR), has
      been evaluated by in vitro experiments with cultures of different cancer cell
      lines. The new metabolic product was found to be non-toxic in all the cell growth
      experiments performed. The absence of cytotoxicity could be explained by the
      observation that the metabolite was not recognized as a substrate by thymidine
      phosphorilase, the enzyme responsible for 5-fluorouracil (5-FU) release from
      doxifluridine, as ascertained by high-performance liquid
      chromatography/ultraviolet (HPLC-UV) analysis of the incubation mixture. The
      biomethylation process leading to N3-Me-5'-dFUR could be considered as a possible
      detoxification pathway, altering the drug bioavailability, in competition with 5'
      dFUR cleavage to the active 5-FU.

PMID- 9608422
TI  - Investigation of the CNS penetration of a potent 5-HT2a receptor antagonist (MDL
      100,907) and an active metabolite (MDL 105,725) using in vivo microdialysis
      sampling in the rat.
AB  - MDL 100,907 is a selective 5-HT2a receptor antagonist which is currently being
      developed for the treatment of schizophrenia. Pharmacokinetic studies of MDL
      100,907 in rats and dogs show that the drug is well absorbed but undergoes
      extensive first-pass metabolism to an active metabolite (MDL 105,725). The
      purpose of this study was to determine concentrations of MDL 100,907 and MDL
      105,725 in the brain extracellular fluid (ECF) after administration of MDL
      100,907. In vivo microdialysis sampling was used to determine the brain
      penetration of both parent (MDL 100,907) and metabolite (MDL 105,725). Animals (n
      = 3/dose) were given 5 i.v. and 50 mg kg-1 oral doses of MDL 100,907. Brain
      medial prefrontal cortex (mPFC) ECF concentrations were determined using
      microdialysis and plasma levels were determined by collecting blood samples
      through an indwelling cannula implanted in the jugular vein. Dialysate samples
      were analyzed using an LC/MS/MS assay. The data presented in this report show
      that the blood brain barrier (BBB) permeability of MDL 100,907 is more than four
      times (4x) that of MDL 105,725 and that MDL 100,907 does not undergo significant
      metabolism to MDL 105,725 in the brain. It appears, from the data presented, that
      MDL 100,907 is the predominant active species present in the brain at high doses.

PMID- 9608423
TI  - Liquid chromatographic analysis in mouse, dog and human plasma; stability,
      absorption, metabolism and pharmacokinetics of the anti-HIV agent 2-chloro-5-(2
      methyl-5,6-dihydro-1,4-oxathiin-3-yl carboxamido) isopropylbenzoate (NSC 615985,
      UC84).
AB  - NSC 615985 (UC 84) has demonstrated anti-HIV activity in the NCI-AIDS antiviral
      screen and was under consideration as an anti-AIDS drug. The compound was
      subsequently shown to be a non-nucleoside reverse transcriptase inhibitor
      (NNRTI). An HPLC method was developed for the analysis of NSC 615985 in mouse,
      dog and human plasma; and was used to study its stability in plasma and blood as
      well as its absorption and metabolism in mice. The method involved precipitation
      of plasma protein with three volumes of methanol followed by HPLC analysis of the
      supernatant. The HPLC analysis was carried out on a reversed-phase Nova-Pak C18
      column with a mobile phase of KH2PO4 (0.01 M; pH 4.8)-acetonitrile (52:48, v/v)
      at a flow rate of 1 ml min-1 and quantification with a UV detector set at 259 nm.
      The lower limit of quantitation was 0.05 microgram ml-1 in 1 ml of dog or human
      plasma or 0.1 microgram ml-1 in 0.5 ml of mouse plasma. NSC 615985 was more
      stable in dog and human plasma than in mouse plasma, and was less stable in blood
      than in plasma of the three species investigated. Following bolus intravenous
      (i.v.) administration at 10 mg kg-1 to male CDF1 mice, NSC 615985 elimination
      followed biexponential kinetics with half-lives of 1 and 7 min, and was
      extensively metabolized. NSC 615985 was very poorly absorbed following oral (PO)
      administration as a suspension in water or in 20% lipid emulsion (Liposyn II).
      Following bolus subcutaneous (s.c.) administration of [14C]NSC 615985 at 10 mg kg
      1, relatively low concentrations of the parent compound were observed in three of
      36 mice. One metabolite was tentatively identified in plasma of both the i.v.-
      and s.c.-treated animals as the sulfoxide of the parent compound. No parent
      compound was detected in the urine of NSC 615985 dosed mice. At least seven
      metabolites were present in urine; one metabolite (constituting 8-14% of urinary
      radioactivity) was tentatively identified as the carboxylic acid resulting from
      the hydrolysis of the isopropyl group from the parent compound. In summary, NSC
      615985 was poorly absorbed following oral administration and extensively
      metabolized and eliminated following i.v. or s.c. administration. This
      unfavorable pharmacokinetic profile of NSC 615985 as well as its pattern of
      activity against NNRTI-resistant strains of HIV-1 precluded its progression to
      clinical trial; however, other members of the general chemical class are
      currently being evaluated by the NCI.

PMID- 9608425
TI  - Determination of 2-chlorodeoxyadenosine (cladribine, 2-CdA) in human plasma by
      liquid chromatography-atmospheric pressure chemical ionization mass spectrometry.
AB  - A sensitive and specific assay based on combined liquid chromatography mass
      spectrometry (LCMS) has been developed and validated for the quantification of 2
      chlorodeoxyadenosine (cladribine, 2-CdA) in human plasma. Sample preparation
      consisted of an extraction with ethyl acetate under basic conditions. The organic
      solvent was evaporated and the residue re-dissolved for analysis. The extracts
      were chromatographed on a base deactivated C-8 column interfaced via the heated
      nebulizer probe to a corona discharge chemical ionization source. The mass
      spectrometer was operated in the positive ion tandem mode. Typical retention
      times were 1.5 and 2.0 min for 2-CdA and a fluorinated analog internal standard
      (IS), respectively. The standard curve was linear from 0.1 to 20 ng ml-1 using a
      1.0 ml sample volume. The resulting chromatograms produced sharp peaks for 2-CdA
      and the IS and showed no endogenous peaks from blank plasma. Peak area ratios of
      2-CdA to IS were used for standard curve regression analysis. This assay
      procedure gave interday mean accuracy results for the standards and quality
      controls that were within 4.9% of target concentrations and interday precision
      results (RSDs) that were less than 5.3%.

PMID- 9608424
TI  - Study of cytokinin metabolism using HPLC with radioisotope detection.
AB  - High performance liquid chromatography (HPLC) with an on-line flow-through
      radioactivity detector was used to monitor the metabolism of cytokinins ([3H]6
      benzylaminopurine and [3H]6-benzylaminopurine riboside) after their incorporation
      into wheat seedlings. The production and conversion of individual metabolites was
      assayed within a short time interval (0.5-3 h). Extraction recoveries from plant
      tissue proved to be 85%. The uptake of both cytokinins was very rapid and
      differences in their metabolism were already perceptible after 30 min. The
      individual metabolites were identified as adenine (Ade), adenosine (Ado),
      benzyladenine-9-glucoside (BA-9G), 6-benzyladenine (BA) and benzyladenosine
      (BAR). The method is very fast, sensitive and very useful for metabolic studies.
      The detection limit was 40 pg (220 Bq) for BA at the level of 2 ng ml-1.

PMID- 9608426
TI  - Study of the stability of erythromycin in a hydrophilic creme basis by liquid
      chromatography.
AB  - The stability of the macrolide antibiotic erythromycin, incorporated at a 2% m/m
      concentration in a hydrophilic creme basis containing 2% m/m of chlorocresol, was
      monitored over a period of 2 months using liquid chromatography as the analytical
      method. Extracts of the creme were analysed using wide-pore poly(styrene
      divinylbenzene) PLRP-S 1000 A as the stationary phase and a mixture of 2-methyl-2
      propanol-acetonitrile-potassium phosphate buffer (pH 11.0; 0.02 M)-water
      (165:30:50:755, v/v/v/v) as the mobile phase. The method showed good selectivity
      towards chlorocresol, erythromycin A, its related substances and degradation
      products. As the pH of the creme containing erythromycin was 8.6, alkaline
      degradation products were expected to be formed. The presence of
      pseudoerythromycin A enol ether was observed after storage of the creme for 1
      week at a temperature of 25 degrees C. After 1 month the content of erythromycin
      was still more than 95%.

PMID- 9608427
TI  - Solution conformation of model peptides with the use of particle beam LC/FT-IR
      spectrometry and electrospray mass spectrometry.
AB  - Solution conformations of the peptides angiotensin I (Ang I) and POMC-X (an
      octapeptide fragment of proopiomelanocortin) were investigated with the use of
      particle beam liquid chromatography/Fourier transform infrared (LC/FT-IR)
      spectrometry. Gradient elution high-performance liquid chromatography (HPLC) with
      mobile phases that contain acetonitrile, 2-propanol, 0.1% heptafluorobutyric acid
      (HFBA) and 0.1% trifluoroacetic acid (TFA) were used. The conformations of both
      peptides were studied in 0.9% sodium chloride injection USP, 5% dextrose in water
      injection USP and sterile water for injection USP. Additional conformational
      studies over a pH range of 2-10, to a temperature of 75 degrees C and after a
      storage time of 24 h were investigated. The studies indicated that the two
      peptides do not behave similarly under identical conditions. It was observed that
      both Ang I and POMC-X had slightly different conformations in the various
      parenteral solutions. It was also shown that the conformation of Ang I changed
      with both pH and temperature while POMC-X was conformationally stable to both
      temperature and pH. The identity of the peptides and the conformationally
      sensitive charge-state intensities of the peptides were investigated with
      electrospray ionization mass spectrometry (ESI/MS). The combination of infrared
      and mass spectrometric data allowed a thorough estimation of solution effects on
      the conformations of the model peptides.

PMID- 9608428
TI  - Application of artificial neural networks in HPLC method development.
AB  - The use of artificial neural networks (ANNs) for response surface modelling in
      HPLC method development for amiloride and methychlothiazide separation is
      reported. The independent input variables were pH and methanol percentage in
      mobile phase. The outputs were capacity factors. The results were compared with a
      statistical method (multiple nonlinear regression analysis). Networks were able
      to predict the experimental responses more accurately than the regression
      analysis.

PMID- 9608429
TI  - Spectrophotometric studies on the photostability of some thiazide diuretics in
      ethanolic solution.
AB  - First derivative and dual-wavelength spectrophotometric methods were used in the
      quantum yield determination of the photochemical decomposition reactions of three
      thiazide diuretics (chlorothiazide, hydrochlorothiazide and trichloromethiazide)
      in ethanolic solution. The radiation absorbed by the compounds was measured using
      iron(III) oxalate actinometry based on absorption spectrophotometry. An apparatus
      is described in which the drugs were irradiated in quartz cuvettes cooled by
      water in a stand built on a magnetic stirrer. The wavelength region available to
      the reaction cuvette was restricted to 313 nm with chemical potassium chromate
      filter solutions and a Corning filter plate. Chlorothiazide proved to be more
      photostable than hydrochlorothiazide and trichloromethiazide in ethanol.

PMID- 9608430
TI  - HPLC determination of ketoprofen enantiomers in human serum using a nonporous
      octadecylsilane 1.5 microns column with hydroxypropyl beta-cyclodextrin as mobile
      phase additive.
AB  - A sensitive and stereospecific high-performance liquid chromatography (HPLC)
      method for the quantitation of ketoprofen enantiomers in human serum was
      developed. The assay involves the use of an octadecylsilane solid-phase
      extraction for serum sample clean-up prior to HPLC analysis. Chromatographic
      resolution of the ketoprofen enantiomers was performed on a nonporous
      octyldecylsilane column with hydroxypropyl beta-cyclodextrin as the mobile phase
      additive. The composition of the mobile phase was 98:2 v/v aqueous 0.1%
      trifluoroacetic acid (TFA), pH 4.00 (adjusted with triethylamine
      (TEA))/acetonitrile containing 10 mM hydroxypropyl beta-cyclodextrin (beta-CD) at
      a flow rate of 0.8 ml min-1. Recoveries of R(-)-ketoprofen was 95.4 +/- 2.16% and
      for S(+)-ketoprofen 96.2 +/- 1.31%. Linear calibration curves were obtained in
      the range 0.025-15 micrograms ml-1 range for each enantiomer in serum. The
      detection limit based on a S/N = 3 ratio was 10 ng ml-1 for each enantiomer in
      serum with ultraviolet detection at 220 nm. The limit of quantitation for each
      enantiomer was 25 ng ml-1. Precision calculated as % relative standard deviation
      (%R.S.D.) and accuracy calculated as % error were in the range 0.2-5.2% and 0.3
      2.2%, respectively, for the R enantiomer and 0.3-6.2 and 0.2-3.2%, respectively,
      for the S enantiomer.

PMID- 9608431
TI  - Spectrophotometric investigation of the formed chelate between timonacic and
      palladium(II) and its analytical applications.
AB  - A simple spectrophotometric method for the determination of timonacic is
      presented. The procedure is based on the chelate formation with palladium(II)
      chloride in buffered medium. The optimum conditions for the complex formation
      were ascertained and the method was developed for the determination of timonacic
      in the concentration range of 28-48 micrograms ml-1. The emperical formula of the
      formed complex was determined, by applying different spectrophotometric methods,
      at optimum pH of 4.8 and an ionic strength of mu = 0.5. The stoichiometric ratio
      was found to be 2:1 (timonacic/palladium) as calculated by the mole ratio,
      continuous variations and Asmus methods. The continuous variations and Nash
      methods were applied for the determination of the conditional stability constant
      of the formed yellow-water soluble complex and was found to be 3.27 x 10(7). The
      proposed methods was found to be suitable for the determination of timonacic in
      bulk and in its pharmaceutical tablets.

PMID- 9608432
TI  - Quantitative determination of acrivastine and pseudoephedrine hydrochloride in
      pharmaceutical formulation by high performance liquid chromatography and
      derivative spectrophotometry.
AB  - In this study, fourth derivative spectrophotometry and high performance liquid
      chromatography (HPLC) have been used and described for the quantitative
      determination of acrivastine (I) and pseudoephedrine hydrochloride (II) in their
      pharmaceutical capsules form (Duact). In the former method, d4A/d gamma 4 values
      were measured in methanol at 315 and 269 nm for (I) and (II) respectively. The
      relative standard deviations (RSD) for the method were found to be 1.16% for (I)
      and 0.94% for (II). The latter method based on reversed phase HPLC system using
      LiChrosorb C18 analytical column. The mobile phase used for separation of (I),
      (II) and internal standard (p-hydroxymethylbenzoate) were the
      water/acetonitrile/methanol/perchloric acid/n-octylamine (500:130:25:13:0.3 v/v)
      and the detection of the compounds in the capsules were at 260 nm using UV
      detector. The RSD for the HPLC method were determined to be 0.79 and 0.88% for
      (I) and (II) respectively. The proposed methods, which give thoroughly comparable
      data, are simple, rapid, and allow precise and accurate results and could be used
      for commercial formulations containing acrivastine and pseudoephedrine
      hydrochloride in combination.

PMID- 9608433
TI  - A radioreceptor assay for the analysis of AT1-receptor antagonists. Correlation
      with complementary LC data reveals a potential contribution of active
      metabolites.
AB  - A reliable and sensitive radioreceptor assay based on rat lung homogenate as
      receptor preparation was developed to determine the angiotensin-II antagonistic
      profile of losartan and its main active metabolite EXP 3174 as well as its
      congeners exemplified by UP 269-6 and SL 91.0102-90 DL. This method proved to be
      precise with an intra- and interday variability of less than 10% and a limit of
      quantification < or = 1 ng ml-1. The analysis of the Ki values in protein-free
      Hepes-buffer versus blank human or rat plasma revealed the distinct high plasma
      protein binding of EXP 3174 which consequently caused a dramatic drop of potency
      from 10-15-fold in the buffer to only about 2-fold in control plasma, when
      compared to the parent compound losartan and the two congeners investigated. Upon
      evaluation of clinical samples by both the reported radioreceptor assay (RRA) and
      the established high-performance liquid chromatography (HPLC), the correlation of
      the normalized data pairs (concentration equivalents) suggested the contribution
      of active metabolites to the angiotensin-II antagonistic effect of SL 91.0102-90
      DL, but not to the effect of UP 269-6. In the context of an extended preclinical
      study in rats, the correlation of RRA with the respective HPLC concentration
      equivalents of losartan and its main active metabolite EXP 3174 confirmed
      previous findings that only losartan and EXP 3174 exert the angiotensin-II-AT1
      receptor blockade without the contribution of other metabolites (P.C. Wong, W.A.
      Price, A.T. Chiu et al., J. Pharmacol. Exp. Ther. 255 (1990) 211-217).

PMID- 9608434
TI  - Biochemical classification of kidney carcinoma biopsy samples using magic-angle
      spinning 1H nuclear magnetic resonance spectroscopy.
AB  - High resolution 1H nuclear magnetic resonance (NMR) spectra using spinning at the
      magic angle (1H MAS NMR) have been obtained on intact normal and pathological
      kidney tissue samples from patients undergoing surgery for renal cell carcinoma
      (RCC). The spectra were measured on ca. 80 mg samples and provided high
      resolution 1H NMR spectra in which effects of dipolar couplings, chemical shift
      anisotropy and magnetic susceptibility differences are minimised thus yielding
      high spectral resolution. Conventional one-dimensional and spin-echo spectra and
      two-dimensional J-resolved, TOCSY and 1H-13C HMQC spectra were also measured on
      selected samples and these allowed the assignment of resonances of endogenous
      substances comprising both cytosolic and membrane components. The tumour tissues
      were characterised principally by an increased lipid content. These are the first
      reported results on human tumour tissues using this technique and the approach
      offers potential for the rapid classification of different types of tumour
      tissue.

PMID- 9608435
TI  - A computer-based expert system designs and analyzes a 2(k - p) fractional
      factorial design for the formulation optimization of novel multicomponent
      liposomes.
AB  - A computer-based technique based on a 2(k - p) fractional factorial design was
      applied for the optimization of recently described multicomponent protective
      liposomal formulations. These formulations contain sodium ascorbate (vitamin C)
      as a model drug sensitive to photochemical oxidation, as well as oil red O and/or
      oxybenzone as oil soluble light absorbers, incorporated into the lipid bilayers
      and sulisobenzone as a water soluble light absorber incorporated into the aqueous
      phase of liposomes. The three light absorbers (present or absent) incorporated in
      multilamellar liposomes and the drug in free or in complexed with alpha
      cyclodextrin form comprised the four factors of the system. The stabilization
      ratio and the percentage entrapment in the liposomes of the vitamin were the two
      response variables of the system to be optimized. The entrapment values were
      calculated for all the materials either spectrophotometrically or by using second
      order derivative spectrophotometry. The response variables were predicted by
      multiple regression equations comprising combinations of the four formulation
      factors. Both the higher entrapment and the higher protection for the drug should
      characterize the optimum formulation.

PMID- 9608436
TI  - Influence and correction of temperature perturbations on NIR spectra during the
      monitoring of a polymorph conversion process prior to self-modelling mixture
      analysis.
AB  - The influence of temperature variations on the rank of a NIR dataset, has been
      investigated by comparing the results of principal component analysis (PCA) and
      evolving factor analysis (EFA), applied to two datasets measured at constant
      temperature and varying temperature. After temperature correction, the
      concentration profiles and spectra were obtained with PCA, SIMPLISMA and the
      orthogonal projection approach (OPA). The same resolution methods were used on
      the dataset measured at constant temperature.

PMID- 9608437
TI  - A ruggedness test strategy for procedure related factors: experimental set-up and
      interpretation.
AB  - A strategy to perform ruggedness tests for mainly procedure related factors is
      described. The different steps in the set-up of the experiments and in the
      interpretation of the results are given. The described strategy is based on a
      number of case studies and allows a statistical interpretation of the
      significance of the effects. It was implemented in a software tool. This original
      strategy was completed with a number of minimal screening designs which reduce
      the number of experiments to perform, but in consequence only allow a limited or
      no statistical interpretation of the effects. Some of the minimal designs are
      expandable to designs with characteristics similar to those of the original
      strategy.

PMID- 9608438
TI  - Pulse polarographic (constant and increasing) determinations of doxazosin in
      pharmaceutical tablets.
AB  - The optimum conditions using DC polarography and the determination of doxazosin
      employing SIAP and SCAP polarographic techniques are described in this study. All
      the experiments were conducted in the supporting electrolyte consisting of 20%
      ethanol (v/v), 0.2 M KCl and 0.2 M acetate buffer at various pH values in order
      to examine the optimum conditions, and pH 3.5 for the determination of doxazosin.
      Well-defined curves were obtained in the pH range of 1.5-7.5. The system was
      diffusional and irreversible at pH 3.5. The calibration studies were performed by
      using SIAP and SCAP polarography and satisfactory results were observed for all
      techniques. Since the sensitivity of SIAP and SCAP techniques were higher than
      the others, the determination of doxazosin was performed in filtered and
      unfiltered tablet solutions containing 4 mg active material. In the analysis of a
      tablet, the relative standard deviations (Srel %) of the techniques are in the
      filtered solutions +/- 0.9 (SIAP), +/- 0.8 (SCAP) and in the unfiltered solutions
      +/- 0.7 (SIAP), +/- 0.8 (SCAP) and no interference was observed during the
      analysis. The determination methods proposed in this study appear to be accurate,
      rapid and practicable. Therefore, these techniques may be suitable for the
      content uniformity tests.

PMID- 9608439
TI  - "Savage inequities": can public/private partnership impact oral health access in
      the United States?

PMID- 9608440
TI  - Dental caries in African preschool children: social factors as disease markers.
AB  - OBJECTIVE: This study investigated the associations between dental caries
      prevalence and severity and social factors in 3- to 5-year-old African children.
      METHODS: Dental caries was diagnosed in natural light using WHO criteria, minors,
      and explorers. Socioeconomic information was obtained by questionnaire. RESULTS:
      The percentages of 3-, 4-, and 5-year-olds with any caries experience were 47
      percent, 58 percent, and 63 percent, respectively. Mean dmfs scores (SD) were
      2.2(3.6), 3.0(3.8), and 3.7(4.1), respectively. Family education was associated
      with caries prevalence (P = .03) and severity (P = .008) in a multivariable
      regression model. CONCLUSION: In the indigenous African group studied, family
      education is a disease marker to target in future caries risk evaluations.

PMID- 9608441
TI  - Prevention of early childhood caries--results of a fluoride toothpaste
      demonstration trial on Chinese preschool children after three years.
AB  - OBJECTIVES: This field demonstration trial evaluates the long-term effects of
      introducing daily toothbrushing with fluoride toothpaste in a Chinese
      kindergarten (test group) compared to caries development in children who had no
      organized preventive program (control group). METHODS: In the test group teacher
      supervised toothbrushing was initiated with 1,000 ppm MFP toothpaste in addition
      to oral health education activities. Test and control children were examined at
      baseline (n = 289, aged 3 years) and annually thereafter. RESULTS: After three
      years, 251 children (87%) were still in the trial. Caries development (dmfs)
      calculation included only those children who were present at both baseline and
      subsequent annual examinations. At baseline the mean dmfs was 4.8 in the test
      group and 6.5 in the control group (NS). After three years the caries increment
      was 6.2 and 8.4 in the test group and the control group, respectively (P < .05).
      Adjusting for reversals, the net caries increment was 3.6 and 6.3, respectively
      (P < .01). Additionally, multiple linear regression analysis indicated that both
      baseline dmfs, the program and plaque level had a significant effect on the net
      caries increment. The use of hierarchical caries severity zones was useful for
      the identification of those children most at risk for further caries development.
      CONCLUSIONS: We conclude that a daily toothbrushing with limited involvement of
      professional staff was feasible in a Chinese kindergarten and that caries
      development was significantly slowed in the test children. Caries severity zones
      may possibly assist in determining levels of intervention.

PMID- 9608442
TI  - Economic evaluation of a pit and fissure dental sealant and fluoride mouthrinsing
      program in two nonfluoridated regions of Victoria, Australia.
AB  - OBJECTIVES: This study assessed the cost effectiveness of a three-year school
      based pit and fissure dental sealant and fluoride mouthrinsing program in two
      nonfluoridated regions in Victoria, Australia. METHODS: The analysis was based on
      a community intervention in five schools comparing an intervention group
      receiving the pit and fissure dental sealant, a weekly fluoride mouthrinsing, and
      an annual oral hygiene education session, with a control group receiving oral
      hygiene education only. The study measured mean differences in DMFS increments
      between study groups. RESULTS: The mean discounted DMFS difference in increment
      (DMFS avoided) between study groups was 1.22 DMFS over three years. The
      incremental cost-effectiveness ratio comparing intervention to control group
      varied between a net savings of $7.00 to a cost of $35.60 per DMFS avoided,
      depending on assumptions used in the analysis. Results were sensitive to
      assumptions on program effectiveness, dental examination rates, and baseline DMFS
      of students. The program became more cost effective with each successive year of
      the program. CONCLUSIONS: The introduction of such a preventive program in
      nonfluoridated regions of Victoria will represent an efficient use of community
      resources. Policy issues that need consideration include whether to target areas
      where adolescents have a history of high dental disease experience, and whether
      dentists or auxiliaries are used as service providers. The need exists for a
      systematic evaluation (including an economic evaluation component) of dental
      prevention and treatment programs in Australia.

PMID- 9608443
TI  - Dental caries and dental fluorosis among schoolchildren who were lifelong
      residents of communities having either low or optimal levels of fluoride in
      drinking water.
AB  - OBJECTIVE: This paper reports findings for dental caries and dental fluorosis in
      8-10- and 13-16-year-old schoolchildren who were lifelong residents of
      communities having either naturally occurring low (Broken Bow and Holdrege, NE; <
      0.3 ppm) or optimal (Kewanee, IL; 1 ppm) levels of fluoride in drinking water.
      METHODS: Findings are reported for participants who received both dental caries
      and dental fluorosis examinations (n = 495). The DMFS and TSIF indices,
      respectively, were used to assess dental caries and dental fluorosis. RESULTS:
      The mean DMFS score adjusted for age, sealant presence, and fluoride use was
      significantly lower in Kewanee (1.8) than was the adjusted mean caries score in
      either Holdrege (2.9) or Broken Bow (3.6). Adjusted mean DMFS scores in Broken
      Bow and Holdrege were not statistically different. The mean percent of fluorosed
      tooth surfaces per person, adjusted for age and use of dietary fluoride
      supplements, was similar in the three communities (approximately 15%); more than
      80 percent of tooth surfaces in all participants were fluorosis-free.
      CONCLUSIONS: Findings from the present study suggest that water fluoridation
      still is beneficial and that dental sealants can play a significant role in
      preventing dental caries. In addition, findings from this survey appear to
      support the premise that the difference in dental fluorosis prevalence between
      fluoridated and nonfluoridated communities has narrowed considerably in recent
      years.

PMID- 9608444
TI  - Racial differences in survival of oral and pharyngeal cancer patients in North
      Carolina.
AB  - OBJECTIVE: This study seeks to determine whether lower survival of black versus
      white oral and pharyngeal cancer patients is due to, or differs by, stage at
      diagnosis. METHODS: Subjects identified through the North Carolina Central Cancer
      Registry included all black and white North Carolina residents diagnosed from
      1987 to 1990 with malignant squamous cell carcinoma of the oral cavity or
      pharynx. Proportional hazards regression models were used to calculate hazard
      ratios for all-cause mortality during the first 18 months after diagnosis,
      adjusting for age, reported histologic grade, site, and several time-dependent
      interactions. RESULTS: Within the first two months after diagnosis, the
      black/white hazard ratio for mortality among those with localized disease was
      11.8 (95% CI = 3.7, 37.5), compared to 6.4 (95% CI = 2.6, 15.8) for those with
      advanced disease. During months 3 to 18 after diagnosis, black/white hazard
      ratios were 2.07 (95% CI = 1.03, 4.18) among those with localized disease and
      1.12 (95% CI = 0.85, 1.47) for those with advanced disease. CONCLUSIONS: In the
      first 18 months after diagnosis, blacks with oral and pharyngeal cancer have
      higher all-cause mortality than whites diagnosed at the same stage of disease.
      Racial differences are greater among those with localized disease than for those
      with more advanced conditions.

PMID- 9608445
TI  - Dental utilization by low-income mothers.
AB  - OBJECTIVE: This study examines the influence of predisposing, enabling, and need
      variables on whether low-income mothers sought dental care during the past year.
      This report is a substudy of mothers and children on their self-reported health
      status, utilization, access, and satisfaction with health care in general.
      METHODS: A convenience sample of 502 mothers and youngest child younger than 6
      years old was administered a face-to-face questionnaire in four Ohio counties.
      Information was collected at county human services offices and WIC clinics
      between November 1995 and July 1996. Using whether or not the mother sought
      dental care as the dependent variable, logistic regression models were created
      for the variables within the predisposing, enabling, and need characteristics
      separately and together. RESULTS: Fewer than one-half of the mothers sought
      dental care during the past year. Variables associated with the predisposing
      characteristic explained little about who sought care. Those mothers who have
      Medicaid coverage are 2.7 times more likely to have a dental visit than those
      without insurance. Moreover, those mothers who perceive any dental need are
      several times less likely to have received dental care than those who have no
      perceived need. CONCLUSIONS: Even among a somewhat homogeneous population of low
      income women, source of payment for dental services and perceived need for dental
      care are discriminating variables in determining who seeks dental care.

PMID- 9608446
TI  - National survey of Korean dentists' knowledge and opinions: dental caries
      etiology and prevention.
AB  - OBJECTIVE: Dentists have the potential to influence what their patients know and
      do regarding dental caries prevention. The practices of dentists and what they
      tell their patients are influenced, in part, by their own knowledge and opinions.
      The purposes of this study were to determine the level of knowledge and opinions
      about caries etiology and prevention among Korean dentists and to describe
      related factors. METHODS: A pretested, 27-item questionnaire was mailed to 2,047
      dentists, selected by a stratified random sampling allocated proportionately. A
      postcard reminder was sent to all dentists after one week. Nonrespondents were
      sent additional complete mailings after three, seven, and nine weeks. The
      response rate was 83 percent (n = 1,700 dentists). RESULTS: Analysis of six
      factors thought to be related to knowledge about caries etiology and prevention
      showed that recent graduates and dentists who worked in public health centers
      were likely to be more knowledgeable about caries etiology and prevention than
      their counterparts (P < .05). In regression analysis of perceived effectiveness
      of caries-preventive procedures for children, recent graduates, males, and
      dentists who worked in public health centers tended to rate caries-preventive
      procedures more effective than other dentists (P < .05). Dentists who had
      experience with school-based preventive programs and dentists in rural areas were
      likely to rate caries-preventive procedures for adults more effective than other
      dentists (P < .05). CONCLUSIONS: Overall, results of this study suggest that the
      majority of dentists do not know current information concerning etiology and
      prevention of dental caries, mechanisms of action of fluoride, and effectiveness
      of preventive procedures for children and adults. Efforts to enhance the level of
      knowledge and practices of Korean dentists about caries prevention should focus
      on strategies to educate older graduates and female dentists, especially those in
      private practice.

PMID- 9608447
TI  - The efficiency of semiannual silane fluoride varnish applications: a two-year
      clinical study in preschool children.
AB  - OBJECTIVE: The aim of this two-year community demonstration trial was to study
      the caries inhibitory effects of semiannual applications of a fluoride varnish in
      preschool children. METHODS: Twenty-four public dental health clinics in the
      county of Halland, Sweden, with 5,137 preschool children, 4 and 5 years of age,
      were matched and equally allocated to a fluoride varnish group (n = 2,535) and a
      reference group (n = 2,602). The children in the fluoride varnish group were
      treated every six months with topical applications of a silane fluoride varnish,
      Fluor Protector (0.1% F), while no fluoride varnish was used in the reference
      group. Both groups received a basic preventive program at annual checkups
      consisting of dietary counseling and instructions to parents to brush their
      children's teeth at least once daily with fluoridated dentifrice. Caries data
      were collected by clinical examinations at baseline and after one and two years.
      RESULTS: Caries prevalence at baseline did not differ significantly between the
      groups. After two years, the mean caries incidence was low and no statistical
      difference was found in the total number of carious and filled surfaces (dfs)
      between the two groups. However, the incidence of approximal lesions (dfsa) was
      significantly lower (P < .05) in the fluoride varnish group than the reference
      group. Children in the fluoride varnish group with dfs scores of 1-4 and > or = 5
      at the start of the study exhibited a statistically significant (P < .05)
      reduction in approximal caries incidence of 19 percent and 25 percent,
      respectively, when compared with the reference group. CONCLUSION: Preschool
      children 4 and 5 years of age with clinical caries who receive semiannual
      applications of a silane fluoride varnish containing 0.1 percent F experience a
      reduced incidence of approximal caries over two years.

PMID- 9608448
TI  - Peer helping/involvement: an efficacious way to meet the challenge of reducing
      alcohol, tobacco, and other drug use among youth?
AB  - Peer-led drug prevention programs for middle school youth are reviewed as to
      whether or not they are a vital resource in an overall effort to minimize the use
      of alcohol, tobacco, and other drugs (ATOD). The paper focuses on the following:
      a) results of a 120-study meta-analysis of school-based drug prevention programs
      and positive program features; b) considerations for falsely concluding that peer
      programs are ineffective; c) features of two model or stellar programs that
      compared interactive (peer leadership) to teacher/researcher-led (non
      interactive) programs that followed National Peer Helpers Association (NPHA)
      Programmatic Standards; and d) suggestions for designing and implementing high
      quality, peer-led programs. The authors conclude that interactive peer
      interventions for middle school students are statistically superior to non
      interactive didactic, lecture programs led by teachers/researchers. Programs
      implemented according to NPHA Programmatic Standards may eliminate Type II (false
      negative) and III ("implementation failure" or ineffectively designed and
      implemented program) errors. Opportunities for prudent application of well
      designed peer programs appropriately implemented and evaluated must remain a
      salient priority.

PMID- 9608449
TI  - Medication administration in schools: the Massachusetts experience.
AB  - In 1991, the School Health Unit of the Massachusetts Department of Public Health
      defined medication administration as a priority policy development area for
      school health. The decision was based on: a) the increased numbers of children
      requiring medications during the school day; b) a lack of consistent standards
      within Massachusetts schools; c) the need to update an outdated statute
      concerning psychotropic medications; and d) the more than 50 weekly telephone
      calls from school health personnel regarding this subject. This article describes
      the Massachusetts experience of developing medication administration regulations
      for public and private schools and implementing the regulations throughout the
      commonwealth. The Massachusetts experience may provide guidance to other states,
      cities, and towns as they address this important child health issue.

PMID- 9608450
TI  - Principles for developing interdisciplinary school-based primary care centers.
AB  - A 50% increase has occurred in the number of school-based primary care centers
      (SBPCCs) in the United States since 1993-94. Public schools offer a well
      established and respected community-based infrastructure within which health
      centers may feasibly be developed. SBPCCs have documented improved access to care
      for underserved children and some initial success in addressing the complex
      morbidities and associated behavioral risk factors of children and adolescents.
      This paper presents five working principles to help communities establish SBPCCs
      that link community health and social services with their educational system. The
      principles encompass community participation, early assessment of community
      needs, integration of health and human services with educational services through
      an interdisciplinary and interagency team approach, development of a business
      plan, and program evaluation. These principles reflect the experiences of 22
      Texas communities which operate 76 SBPCCs. They should prove helpful to many
      other communities and states that propose to develop, finance, and evaluate
      school-based, interdisciplinary health care and prevention services.

PMID- 9608451
TI  - Heart Partners: a strategy for promoting effective diffusion of school health
      promotion programs.
AB  - Heart Partners uses a straightforward, interpersonal approach to increase
      acceptance and use of innovations in school health promotion. In accord with the
      linkage model of innovation diffusion, developers of a new program or technology
      (i.e., resource system) simply designate and train selected members to be
      recruiters and allies of individual advocates at the campus-level (i.e., user
      system). Linkage is supported by supplying advocates and allies with guidelines
      and materials that encourage ongoing, interactive, interpersonal partnerships to
      promote effective implementation of the new technology at the school. Empirical
      assessment of this simple strategy implemented by the Texas Affiliate of the
      American Heart Association showed a twofold to fourfold increase in actual use
      and reach of school health promotion packages, with an average reported volunteer
      time of less than three hours per month.

PMID- 9608452
TI  - Are elementary schools teaching children to prefer candy but not vegetables?

PMID- 9608453
TI  - Bringing urban legends into the classroom.

PMID- 9608454
TI  - The Harrison Healthy Kids Center: a comprehensive elementary school-based health
      program.

PMID- 9608455
TI  - Assistive technology benefits for students with disabilities.

PMID- 9608456
TI  - Anterior cruciate ligament graft positioning, tensioning and twisting.
AB  - This paper reports on a scientific workshop to study anterior cruciate ligament
      (ACL) reconstruction. The aim is to present recommendations for ACL
      reconstruction methods that will be of use for surgeons. A study of knee anatomy
      and graft placement concluded that the tibial attachment must be posterior enough
      to avoid graft impingement against the femur, and methods to attain this were
      presented. On the femur, poor graft placement leads to excessive changes of the
      graft attachment site separation distance as the knee flexes, and the worst case
      corresponds to the attachment being too far anterior. It was agreed that there
      were typical patterns of graft tension changes as the knee flexes, and that
      grafts should be tensioned close to full knee extension. A typical tensioning
      protocol would be 60 N tension applied at 10 degrees of flexion. It was
      recognised that graft remodelling caused uncontrollable tension changes post
      operation. Graft twisting, to recreate the anatomical spiral of ACL fibres seen
      in the flexed knee, was also discussed.

PMID- 9608457
TI  - Drill hole position in endoscopic anterior cruciate ligament reconstruction.
      Results of an advanced arthroscopy course.
AB  - In 24 cadaver knees the anterior cruciate ligament (ACL) was replaced by a bone
      tendon-bone patellar tendon autograft in an endoscopic technique. This was
      carried out during an advanced arthroscopy course after intensive instruction and
      practice on a plastic model. When the knees were opened and evaluated according
      to the recent orthopaedic literature, only four good results with correct tunnels
      and a non-impinging graft were found. In 12 knees the femoral tunnel was too far
      anterior (10) or had broken through the posterior femoral cortex (2). In 6 knees
      the tibial tunnel was too far anterior (2) or too far posterior (4). The
      notchplasty was insufficient in 6 knees. We conclude that endoscopic ACL
      reconstruction cannot be mastered after attending a course alone. Expert help is
      necessary during the first clinical cases.

PMID- 9608458
TI  - Biomechanical properties of the central third patellar tendon graft: effect of
      rotation.
AB  - The results of this study suggest that the central third of the patellar tendon
      may be stronger than previously reported. The mean ultimate load of a 15-mm bone
      patellar tendon-bone composite was 4389 N (+/- 709 N); of the 10-mm wide
      composites, 2977 N (+/- 516 N); and of the 7-mm composites, 2238 N (+/- 316 N).
      Twisting the graft 90 degrees increased the strength (P < 0.05). Further twisting
      to 180 degrees had no significant effect compared with twisting to 90 degrees.
      This study supports the practice of using smaller (10 mm) bone-patellar tendon
      bone grafts to avoid the potential complications of patellar fracture and graft
      impingement in the notch, and suggests the value of rotating the graft prior to
      tibial fixation.

PMID- 9608459
TI  - Factors affecting graft excursion patterns in endoscopic anterior cruciate
      ligament reconstruction.
AB  - The effect of femoral guide rotation in endoscopic anterior cruciate ligament
      (ACL) reconstruction is reviewed based on a previous report. The effect of varied
      offsets of the femoral guide (5.5 and 7.0 mm) are described. This is one of the
      few isometry studies to evaluate the knee through a practically full range of
      motion (0 degree-120 degrees). A 7-mm offset guide rotated to the 12:00 position
      yields the best single fiber and graft excursion patterns (P < 0.05). A 5.5-mm
      offset guide yields inferior single fiber and graft excursion patterns. Single
      fiber and graft isometry are similar but not identical in endoscopic ACL
      reconstruction. Centering the single fiber in the tibial tunnel has little effect
      on isometry patterns, demonstrating that the more posterior tibial positions
      needed for endoscopic reconstruction are acceptable from an isometry standpoint.

PMID- 9608460
TI  - Maximum unloaded length (MUL) and graft force as criteria for anterior cruciate
      ligament graft fixation.
AB  - The biomechanical determinants of graft force after ACL reconstruction are
      reviewed. It is proposed that the two primary determinants are tunnel location
      and "maximum unloaded length" (MUL), defined as the distance between the origin
      and insertion tunnels when the graft just begins to carry load. MUL and graft
      stiffness determine graft force for a given flexion angle and external load.
      Although several variables can affect MUL, such as pretension level, flexion
      angle at pretension, and direction of tension, one variable is important,
      fixation position of the graft relative to the bone. It is proposed that a more
      rational basis for establishing graft fixation, rather than isometry, is graft
      force, reflecting the choice of MUL. Setting graft force with a device that
      adjusts MUL allows adjustment of the graft force to a chosen level of fixed
      pretension and joint laxity, while avoiding overstressing during passive range of
      motion due to poor tunnel placement.

PMID- 9608461
TI  - Significance of graft tension in anterior cruciate ligament reconstruction. Basic
      background and clinical outcome.
AB  - The purpose of this paper is to review scientific evidence that graft tension
      affects remodelling of the autograft in ligament reconstruction. The in situ
      freezing model of the patellar tendon, an ideal patellar tendon autograft model,
      demonstrated that subsequent cellular proliferation following fibroblast necrosis
      reduces the mechanical properties of the autograft. Stress shielding enhances
      reduction of the strength in the once-frozen patellar tendon. The strength of the
      patellar tendon also changes depending on the degree of stress shielding.
      Transmission electron micrographs revealed that the number of small-diameter
      fibrils decreases in the stress-shielded tendons compared with non-stress
      shielded tendons after in situ freezing. Restressing essentially restores the
      mechanical properties of patellar tendon autografts even if the strength has been
      much reduced by complete stress shielding. The effects of restressing may depend
      on the period of stress shielding applied before restressing. Unphysiologically
      high tension significantly reduces the mechanical properties of the in situ
      frozen anterior cruciate ligament (ACL). Therefore, not only stress-deprivation
      but also stress-enhancement significantly affect the mechanical properties of
      tendon autografts. Results of in vivo and in vitro studies suggest that cyclic
      tensile loading may inhibit the deterioration in mechanical strength of the
      transplanted tendon. Clinically, our prospective randomized study demonstrated
      that a relatively high initial tension reduces the postoperative anterior laxity
      of the knee joint after ACL reconstruction using the doubled autogenous hamstring
      tendons connected in series with polyester tapes, when the tension applied is
      less than 80 N. Our experimental and clinical results indicate that the initial
      tension is one of the significant factors that affect the results of ACL
      reconstruction, although the optimal initial tension for the other graft
      materials still remains unknown.

PMID- 9608462
TI  - Anterior cruciate ligament graft tensioning versus knee stability.
AB  - Positioning of the graft for anterior cruciate ligament (ACL) reconstruction and
      securing the graft at various degrees of knee flexion are interrelated factors
      when attempting to restore a knee's normal kinematics. The interrelationships
      between graft positioning on the femur and tibia (graft 'isometricity'); securing
      the graft at various positions of knee flexion; and the resulting restoration or
      disruption of the knee kinematics were studied on ten fresh frozen cadaveric knee
      specimens. Well placed ('isometric') grafts appeared to restore almost normal
      knee kinematics regardless of the position of the knee at the time of securing
      the grafts. This was, however, not the case in non-ideally placed grafts.
      'Nonisometric' ACL substitutes which became taut in extension, overconstrained
      the knee if the graft was secured in flexion. If the same graft was secured in
      extension, increased joint laxity in flexion occurred. In contrast,
      'nonisometric' ACL substitutes which became taut in flexion overconstrained the
      knee if the graft was secured in extension. If the same graft was secured in
      flexion, the graft became slack during extension.

PMID- 9608463
TI  - Anatomic versus non-anatomic tibial fixation in anterior cruciate ligament
      reconstruction with bone-patellar tendon-bone graft.
AB  - We prospectively compared two series of 30 anterior cruciate ligament (ACL)
      reconstructions each where the bone-patellar tendon-bone graft was alternately
      fixed at the level of the tibial plateau (group A; anatomic fixation) or distal
      to the plateau level (group B; non-anatomic fixation). In group A, a 35-mm-long
      tibial tuberosity bone block was harvested. The distal 10-15 mm were resected and
      fixed proximally to the undersurface of the tendon to shorten it. After an
      average 18 months' follow-up, there were no significant differences between the
      two groups concerning subjective evaluation, symptoms, range of motion and
      objective stability. Tibial tuberosity pain was more frequent in group A (53% vs
      17%, P = 0.01). Radiographic evaluation showed that tibial tunnel enlargement was
      less frequent in group A (23% vs 43%, P = 0.02). There was no correlation between
      tunnel enlargement and objective stability. In conclusion, fixation of the graft
      at the tibial plateau level did not improve objective stability in this study.
      Because of the greater technical difficulty and occurrence of tibial tuberosity
      pain, this technique is not recommended.

PMID- 9608464
TI  - Principles for placing the tibial tunnel and avoiding roof impingement during
      reconstruction of a torn anterior cruciate ligament.
AB  - Reconstruction of a form anterior cruciate ligament (ACL) cannot be successful
      without a properly placed tibial tunnel. Preventable complications such as
      anterior knee pain, effusions, extension loss, and recurrent instability can
      occur when the tibial tunnel is improperly placed and the roof and notchplasty
      are insufficient. This article reviews the principles for anatomic placement of
      the tibial tunnel so that complications associated with impingement of the ACL
      graft on the intercondylar roof can be prevented. Five factors that contribute to
      roof impingement are discussed, including differences in the size and shape of
      the ACL and the graft, variability in knee extension and roof angle between
      patients, inability to view the contact between the intercondylar roof and the
      graft, accentuation of roof impingement from anterior tibial translation caused
      by quadriceps contraction, and the use of tibial guides that rely on soft-tissue
      landmarks. A surgical technique is presented which consistently places the tibial
      tunnel in the pathway of the normal ACL (i.e., anatomic placement) and avoids
      roof impingement. The indications and need for roof- and wallplasty are
      discussed.

PMID- 9608465
TI  - Effect of cyclic preconditioning on the tensile properties of human quadriceps
      tendons and patellar ligaments.
AB  - Preconditioning of soft tissues has become a common procedure in tensile testing
      to assess the history dependence of these viscoelastic materials. To our
      knowledge, this is the first study comparing tensile properties of soft tissues
      before and after cyclic preconditioning with high loads. Sixteen quadriceps
      tendon-bone (QT-B) complexes and 16 patellar ligament-bone (PL-B) complexes from
      a young population (mean age 24.9 +/- 4.4 years) were loaded to failure with a
      deformation rate of 1 mm/s. Half of the QT-B and the PL-B complexes underwent 200
      uniaxial preconditioning cycles from 75 to 800 N at 0.5 Hz before ultimate
      failure loading. High-load preconditioning was made possible by the development
      of a highly reliable and easy-to-use cryofixation device to attach the free
      tendon end. PL-B complexes were more influenced by preconditioning than the QT-B
      complexes. Ultimate failure load, stiffness at 200 N and stiffness at 800 N were
      significantly higher for PL-B complexes after preconditioning, while the
      structural properties of QT-B complexes exhibited no significant alterations. The
      values of the mechanical properties like Young's modulus at 200 N and 800 N were
      much higher for both preconditioned specimen groups. In addition, ultimate stress
      was augmented by preconditioning for PL-B complexes. Hysteresis and creep effects
      were highest during the first few loading cycles. More than 160 cycles were
      needed to reach a steady state. Beyond 160 cycles there was no further creep, and
      hysteresis was almost constant. Creep values were 2.2% of the initial testing
      length for the QT-B and 3.2% of the initial testing length for the PL-B
      complexes. The effect of cyclic preconditioning seems to be caused by progressive
      fiber recruitment and by alterations of the interstitial fluid milieu.

PMID- 9608466
TI  - The immediate postoperative kinematic state after anterior cruciate ligament
      reconstruction with increasing peroperative tension.
AB  - The last steps in anterior cruciate ligament (ACL) reconstruction are tensioning
      and fixation of the ligament. However, how much tension should be applied to the
      ligament in general or in each individual and in which position the ligament
      should be fixed remain unanswered questions. The purpose of this study was to
      investigate the effect of increasing ligament tension on the immediate
      postoperative kinematic state of the ACL-reconstructed knee. Nine cadaver knees
      were mounted in a mechanical measuring device based on a redesign of the Genucom
      knee testing system, so that the femur was fixed to a force plate and the moving
      tibia to a goniometer arm for registration of movement. The ligament was attached
      on the tibial side to a Kistler load cell and a turn-buckle for adjustment of
      ligament tension. The ligament was tensioned at 30 degrees of flexion with 5, 33,
      66, 99 and 132 N. The cadaver knees were tested with an intact ACL, after
      sacrifice of the ACL and after reconstruction of the ACL with an ABC ligament.
      Results showed that there was a significant decrease in knee motion when the
      tension was higher than 33 N. This resulted in an overconstrained knee with less
      anteroposterior translation, internal-external rotation and varus-valgus movement
      compared with the uninjured knee.

PMID- 9608467
TI  - In vitro testing protocols for the cruciate ligaments and ligament
      reconstructions.
AB  - The techniques that have been used to characterize the biomechanical behavior of
      the knee, cruciate ligaments, and cruciate ligament replacements differ, making
      comparisons between studies difficult or, at times, impossible. Therefore, it is
      important to standardize the testing protocols and techniques that describe the
      biomechanical behavior of the knee and cruciate ligaments. This will allow
      investigators to express opinions with respect to the interpretation of data,
      rather than based on differences between testing techniques. Standardized
      techniques are proposed to locate the origins of the tibial and femoral
      coordinate systems, and thus, allow comparisons of knee kinematics (e.g.,
      displacements and rotations) between investigations. Standard techniques that can
      be used to measure the load-displacement behavior of the knee are described, and
      important considerations that should be appreciated with respect to preparing and
      testing of the joint are summarized. It is important to evaluate the single cycle
      load-to-failure characteristics and the cyclic loading response of an anterior
      cruciate ligament graft, and techniques to evaluate cruciate ligament graft
      fixation are proposed. The strengths of different models to characterize the
      biomechanical behavior of the knee are reviewed.

PMID- 9608468
TI  - Effects of motion blurring in x-ray fluoroscopy.
AB  - In conventional fluoroscopy, continuous x-ray exposure blurs moving objects,
      while in pulsed fluoroscopy, short duration x-ray pulses acquire images without
      motion blur. Many perception experiments on noisy image sequences are consistent
      with low-pass temporal filtering by the human visual system, and this is
      anticipated to cause visual system "blurring" of moving objects. With moving
      cylinders in spatially white noise, we simulated 30 acq/s (acquisitions per
      second), continuous fluoroscopy having both x-ray and visual system motion blur.
      We also simulated pulsed fluoroscopy at 30 acq/s (pulsed-30) having visual system
      but not x-ray system motion blur. For both continuous and pulsed-30 acquisitions,
      with increasing velocity, detectability of small cylinders decreased by as much
      as approximately 50%, while detectability of large cylinders increased and then
      decreased. Detectability of pulsed-30 was only slightly higher than continuous,
      indicating that visual system motion blurring dominated x-ray system blurring.
      For the case of stationary objects, blurring greatly reduced detectability,
      indicating that last-image-hold of moving objects deteriorates with continuous
      acquisitions. With no free parameters, a human observer model with an
      independently measured spatio-temporal contrast sensitivity function accurately
      described all effects.

PMID- 9608469
TI  - Image restoration and reconstruction with a Bayesian approach.
AB  - We have extended Johnson's Bayesian method for image restoration and
      reconstruction by introducing diagonal line sites, using symmetric neighborhood
      configurations, and employing an additional hyperparameter for estimation of line
      sites. A general formulation for arbitrary neighborhood configurations was
      derived. The major part of this paper deals with the conduct of computer
      simulations intended to examine the effect of the hyperparameters, the diagonal
      line sites, and the size of the neighborhood configuration on the performance of
      the proposed Bayesian method. We show that, for optimal performance, distinct
      hyperparameters should be used for the intensity sites and line sites. The
      results also suggest that a large neighborhood configuration should be used. By
      comparing the near-optimal restored images, we demonstrated that the use of
      diagonal line sites, along with the symmetric configurations thus made possible,
      can effectively remove the blocky edge artifacts and produce images of better
      quality. When the method was applied to positron emission tomography (PET) image
      reconstruction, our results showed that the quality of the reconstructed images
      was improved for both computer-simulated and real patient PET data.

PMID- 9608470
TI  - Signal, noise power spectrum, and detective quantum efficiency of indirect
      detection flat-panel imagers for diagnostic radiology.
AB  - The performance of an indirect-detection, active matrix flat-panel imager (FPI)
      at diagnostic energies is reported in terms of measured and theoretical signal
      size, noise power spectrum (NPS), and detective quantum efficiency (DQE). Based
      upon a 1536 x 1920 pixel, 127 microns pitch array of a-Si:H thin-film transistors
      and photodiodes, the FPI was developed as a prototype for examination of the
      potential of flat-panel technology in diagnostic x-ray imaging. The signal size
      per unit exposure (x-ray sensitivity) was measured for the FPI incorporating five
      commercially available Gd2O2S:Tb converting screens at energies 70-120 kVp. One
      dimensional and two-dimensional NPS and DQE were measured for the FPI
      incorporating three such converters and as a function of the incident exposure.
      The measurements support the hypothesis that FPIs have significant potential for
      application in diagnostic radiology. A cascaded systems model that has shown good
      agreement with measured individual pixel signal and noise properties is employed
      to describe the performance of various FPI designs and configurations under a
      variety of diagnostic imaging conditions. Theoretical x-ray sensitivity, NPS, and
      DQE are compared to empirical results, and good agreement is observed in each
      case. The model is used to describe the potential performance of FPIs
      incorporating a recently developed, enhanced array that is commercially available
      and has been proposed for testing and application in diagnostic radiography and
      fluoroscopy. Under conditions corresponding to chest radiography, the analysis
      suggests that such systems can potentially meet or even exceed the DQE
      performance of existing technology, such as screen-film and storage phosphor
      systems; however, under conditions corresponding to general fluoroscopy, the
      typical exposure per frame is such that the DQE is limited by the total system
      gain and additive electronic noise. The cascaded systems analysis provides a
      valuable means of identifying the limiting stages of the imaging system, a tool
      for system optimization, and a guide for developing strategies of FPI design for
      various imaging applications.

PMID- 9608471
TI  - Automated flight path planning for virtual endoscopy.
AB  - In this paper, a novel technique for rapid and automatic computation of flight
      paths for guiding virtual endoscopic exploration of three-dimensional medical
      images is described. While manually planning flight paths is a tedious and time
      consuming task, our algorithm is automated and fast. Our method for positioning
      the virtual camera is based on the medial axis transform but is much more
      computationally efficient. By iteratively correcting a path toward the medial
      axis, the necessity of evaluating simple point criteria during morphological
      thinning is eliminated. The virtual camera is also oriented in a stable viewing
      direction, avoiding sudden twists and turns. We tested our algorithm on
      volumetric data sets of eight colons, one aorta and one bronchial tree. The
      algorithm computed the flight paths in several minutes per volume on an
      inexpensive workstation with minimal computation time added for multiple paths
      through branching structures (10%-13% per extra path). The results of our
      algorithm are smooth, centralized paths that aid in the task of navigation in
      virtual endoscopic exploration of three-dimensional medical images.

PMID- 9608472
TI  - X-ray imaging using amorphous selenium: determination of Swank factor by pulse
      height spectroscopy.
AB  - The use of photoconductors, especially amorphous selenium (a-Se), in x-ray
      imaging is currently of interest. A critical performance parameter of an imaging
      detector is the Swank factor for degradation of the signal to noise ratio, or
      DQE(0), due to variations in the detector response. The Swank factor is evaluated
      from measured pulse height spectra generated by the absorption of monoenergetic x
      ray photons. The spectra show an additional width over previous theoretical
      expectations, but the Swank factor is still close to the high values previously
      predicted theoretically.

PMID- 9608473
TI  - Comparison of selected ultrasound performance tests with varying overall receiver
      gain and dynamic range, using conventional and magnified field of view.
AB  - Most ultrasound (US) scanner vendors currently offer a feature that allows a
      region of the ultrasound image to be magnified or zoomed. Although the methods of
      magnification vary among vendors, the ability to "zoom in" on a selected portion
      of the image has gained clinical acceptance. However, using this feature
      introduces additional steps in the quality assurance (QA) measurement procedures.
      No studies exist that demonstrate the advantage of a magnified field of view
      (FOV) over the conventional FOV for QA purposes. The purpose of this study was to
      investigate the influence of a magnified versus nonmagnified FOV on various
      common QA performance tests as a function of the overall receiver gain and
      dynamic range. Additionally, since the performance tests are subject to
      variations caused by scanner settings, sets of QC tests were recorded using
      several different scanner settings to investigate any change in the sensitivity
      of the QC measurements with respect to the magnified and nonmagnified fields of
      view. The lateral and axial resolution, slice thickness, and caliper accuracy
      (vertical and horizontal) as a function of varying overall receiver gain and
      dynamic range, were obtained using conventional (no zoom) as well as a magnified
      (zoom) field of view (FOV). Each measurement was performed three times by a
      single observer using a 4 MHz "vector" format transducer on a single diagnostic
      medical ultrasound scanner. The results show no statistical significance in the
      variability of most recorded masurements when using the conventional versus the
      magnified FOV. However, in some cases, such as lateral resolution, the average
      value measured using the magnified FOV was typically 0.5 mm lower than when using
      a conventional FOV.

PMID- 9608474
TI  - Estimating the spatial autocorrelation function for ultrasound scatterers in
      isotropic media.
AB  - The autocorrelation function pertaining to spatial distributions of ultrasonic
      scatterers in soft tissue is believed to contain useful information related to
      tissue morphology. A simple processing method applied to radio-frequency echo
      signals estimates this function for a sample having isotropic scattering
      conditions. It utilizes backscattered echo signals from the sample and echo
      signals from a reference object having defined scattering properties. The ratio
      of the echo signal power spectrum from the sample to the echo signal power
      spectrum from the reference object is obtained, and corrected for attenuation
      differences between the two media. This yields a "form factor" for the sample,
      whose inverse Fourier transform is the autocorrelation function. The method was
      tested using tissue-mimicking samples for which spatial autocorrelation functions
      could be modeled from the dimensions of embedded scatterers. The shapes of the
      measured autocorrelation functions were in reasonable agreement with those
      estimated, although measured functions overestimated the function at small lag
      distances. Scatterer diameters estimated from the zeros of the autocorrelation
      function agreed to within 6% of expected values when the measurement system
      bandwidth satisfied minimal criteria.

PMID- 9608475
TI  - A technique for the quantitative evaluation of dose distributions.
AB  - The commissioning of a three-dimensional treatment planning system requires
      comparisons of measured and calculated dose distributions. Techniques have been
      developed to facilitate quantitative comparisons, including superimposed
      isodoses, dose-difference, and distance-to-agreement (DTA) distributions. The
      criterion for acceptable calculation performance is generally defined as a
      tolerance of the dose and DTA in regions of low and high dose gradients,
      respectively. The dose difference and DTA distributions complement each other in
      their useful regions. A composite distribution has recently been developed that
      presents the dose difference in regions that fail both dose-difference and DTA
      comparison criteria. Although the composite distribution identifies locations
      where the calculation fails the preselected criteria, no numerical quality
      measure is provided for display or analysis. A technique is developed to unify
      dose distribution comparisons using the acceptance criteria. The measure of
      acceptability is the multidimensional distance between the measurement and
      calculation points in both the dose and the physical distance, scaled as a
      fraction of the acceptance criteria. In a space composed of dose and spatial
      coordinates, the acceptance criteria form an ellipsoid surface, the major axis
      scales of which are determined by individual acceptance criteria and the center
      of which is located at the measurement point in question. When the calculated
      dose distribution surface passes through the ellipsoid, the calculation passes
      the acceptance test for the measurement point. The minimum radial distance
      between the measurement point and the calculation points (expressed as a surface
      in the dose-distance space) is termed the gamma index. Regions where gamma > 1
      correspond to locations where the calculation does not meet the acceptance
      criteria. The determination of gamma throughout the measured dose distribution
      provides a presentation that quantitatively indicates the calculation accuracy.
      Examples of a 6 MV beam penumbra are used to illustrate the gamma index.

PMID- 9608476
TI  - A generic off-axis energy correction for linac photon beam dosimetry.
AB  - Cooperative clinical trial group protocols frequently require off-axis point dose
      calculations. The Radiological Physics Center uses the calculative technique
      developed by Hanson et al. [Med. Phys. 7, 145-146 (1980); 7, 147-150 (1980)] to
      verify these calculations. In order to correct for off-axis energy changes, this
      technique requires off-axis half-value layer data, HVL, as a function of off-axis
      ray angle for the specific beam. This paper presents a formulism based on HVL
      mesurements on a limited number of therapy beams, which allows the calculation of
      an off-axis energy-correction factor for any clinical photon beam created by a
      linear accelerator using conventional flattening filters.

PMID- 9608477
TI  - On compensator design for photon beam intensity-modulated conformal therapy.
AB  - Recently the compensator has been shown to be an in expensive and reliable dose
      delivery device for photon beam intensity-modulated radiation therapy (IMRT). The
      goal of IMRT compensator design is to produce an optimized primary fluence
      profile at the patient's surface obtained from the optimization procedure. In
      this paper some of the problems associated with IMRT compensator design,
      specifically the beam perturbations caused by the compensator, are discussed. A
      simple formula is derived to calculate the optimal compensator thickness profile
      from an optimized primary fluence profile. The change of characteristics of a 6
      MV beam caused by the introduction of cerrobend compensators in the beam is
      investigated using OMEGA Monte Carlo codes. It is found that the compensator
      significantly changes the energy spectrum and the mean energy of the primary
      photons at the patient's surface. However, beam hardening does not have as
      significant an effect on the percent depth dose as it does on the energy
      spectrum. We conclude that in most situations the beam hardening effect can be
      ignored during compensator design and dose calculation. The influence of the
      compensator on the contaminant electron buildup dose is found to be small and
      independent of the compensator thickness of interest. Therefore, it can be
      ignored in the compensator design and included as a correction into the final
      dose distribution. The scattered photons from the compensator are found to have
      no effect on the surface dose. These photons produce a uniform low fluence
      distribution at the patient's surface, which is independent of compensator shape.
      This is also true for very large fields and extremely asymmetric and nonuniform
      compensator thickness profiles. Compared to the primary photons, the scattered
      photons have much larger angular spread and similar energy spectrum at the
      patient's surface. These characteristics allow the compensator thickness profile
      and the dose distribution to be calculated from the optimized fluence profile of
      primary photons, without considering the scattered photons.

PMID- 9608478
TI  - An efficient method for small field treatment dose calculation for stereotactic
      radiosurgery using a LINAC.
AB  - The normal procedure for a physician-physicist team designing a treatment plan
      for multiarc stereotactic radiosurgery is the trial-and-error approach of
      changing the collimator size and the location of the isocenter of radiation and
      viewing the isodose curves on two-dimensional computed tomography (CT) or
      magnetic resonance imaging (MRI) image planes. Automatic optimization procedures
      have also been used to optimize beam weight or beam size. However, either process
      is very time consuming. To improve the speed of the dose calculation, a random
      sampling method has been proposed. Unfortunately, the sampled values of an
      objective function are different from one sample to another. Such a sampling
      method cannot be used in automatic optimization because the next move in an
      optimization process is based on the current and past objective function values.
      To this end, an adaptive method based on the size of the collimators is proposed
      and used to determine a small volume in the shape of a hollow sphere for which
      the dose is calculated. With an appropriate choice of an adaptive hollow sphere,
      the objective function calculated based on such a hollow sphere is the same as
      that calculated with the traditional three-dimensional (3-D) cube matrix.
      However, with the new adaptive method, the speed of calculating a dose can be
      improved by a factor of 4 to a factor of 100. Because of the improvement in the
      speed of calculating a treatment dose, the new adaptive hollow sphere method for
      calculating a treatment dose can be used routinely in designing a treatment plan.

PMID- 9608479
TI  - Photonuclear production in tissue for different 50 MV bremsstrahlung beams.
AB  - Calculations of photonuclear production in "tissue approximation" and the
      relative heavy particle dose to photon dose at dose maximum in water have been
      performed. Different 50 MV spectra based on a scanned beam technique to produce
      flat photon fields were used. These spectra were calculated with the Monte Carlo
      method and correspond to different target configurations and scan patterns.
      Photonuclear cross sections of neutron, proton, and alpha production for oxygen,
      nitrogen, and carbon are taken from the literature. Activation measurements using
      a HpGe detector have been used to verify the calculations. The relative heavy
      particle dose to photon dose was found to be 0.30%-0.42%, depending on the
      spectra used, and the estimated uncertainty was 20%. A relative biological effect
      (RBE) of 1.01-1.03 in "tissue approximation" for 50 MV were estimated using a RBE
      for neutron and protons of 2-5 and 4-10 for alpha particles.

PMID- 9608480
TI  - X-ray quantum limited portal imaging using amorphous silicon flat-panel arrays.
AB  - We have measured the linearity, spatial resolution (MTF), noise (NPS), and signal
      to-noise characteristics (DQE) of an electronic portal imaging device (EPID)
      based on an amorphous silicon flat-panel array. The array has a 128 x 128-pixel
      matrix and each pixel is 0.75 x 0.75 mm2 in dimension so the array covers an area
      of 96 x 96 mm2. The array acts like a large area light sensor and records the
      optical signals generated in a metal plate/phosphor screen x-ray detector when
      the detector is irradiated by a megavoltage x-ray beam. In addition,
      approximately 0.5% of the total signal is generated by nonoptical processes. The
      noise measurements show that the device is quantum noise limited with the noise
      power generated by the x-ray quanta being up to 100 times greater than the noise
      added by the external readout electronics and flat-panel light sensor itself.
      However, the flat-panel light sensor does reduce the spatial resolution (compared
      to a perfect optical sensor with infinitesimal pixel size) because of its
      moderate pixel size and because optical spread can occur in the transparent glues
      used to attach the phosphor screen to the flat-panel light sensor. The response
      of the sensor is very linear and does not suffer from the glare phenomenon
      associated with TV camera-based EPIDs--characteristics which suggest that the
      amorphous silicon EPID will be well suited to transit dosimetry. Nevertheless,
      some limitations need to be overcome before these devices can be used clinically.
      These include developing larger flat-panel light sensors, the elimination of
      "noisy" pixels with high dark signal, and improvements in the uniform sensitivity
      of the sensors. This last requirement is only needed for transit dosimetry
      applications where it would greatly simplify calibration of the device. In
      addition, an image acquisition scheme must be developed to eliminate artifacts
      created by the pulsed x-ray beam generated by linear accelerators. Despite these
      limitations, our studies suggest that the amorphous silicon EPIDs are very well
      suited to portal imaging.

PMID- 9608481
TI  - Determination of rotations in three dimensions using two-dimensional portal image
      registration.
AB  - The relative relationships among anatomic features visualized on planar
      radiographic images change due to rotations of the patient out of the imaging
      plane. These changes can be predicted a priori from a three-dimensional
      radiographic model of the patient. In this study we assess the feasibility of
      using that information together with a planar image feature alignment tool to
      account for out-of-plane rotations in the evaluation of subsequent clinical
      patient images. A series of digitally reconstructed radiographs (DRRs) with known
      patient rotations was generated from a computed tomography scan of an
      anthropomorphic head phantom. Fixed anatomic features were extracted, as seen in
      the DRRs of rotated anatomy and entered into a database. Alignment of features
      from test radiographs with those from an entry in this database yielded an
      estimate of rotation out of plane (database entry that resulted in the best fit
      via planar transformation) along with the planar components of setup errors in
      the rotated plane. Tests using DRRs and films show that it is possible to select
      anatomic features in AP skull radiographs with position and orientation sensitive
      to out-of-plane rotation.

PMID- 9608482
TI  - 125I brachytherapy k-edge dose enhancement with AgTPPS4.
AB  - Photon activation is a radiotherapy technique in which an element is added to the
      absorbing medium to raise the probability that a photoelectric interaction will
      occur, thus causing an increase in the absorption of ionizing radiation. Binding
      energies of key elements within an absorbing medium are closely matched with the
      incident photon energies to maximize the production of free electrons and
      subsequent absorption of their kinetic energies. The purpose of this research was
      to quantify potential dose enhancement using a silver tetraphenyl sulfonato
      porphyrin (AgTPPS4) in tumors as a photon activator for use with interstitial
      125I brachytherapy. A three-dimensional Monte Carlo dosimetry model was developed
      using the EGS4 coding system. The photon source was modeled using spectral gamma
      emissions from models 6702 or 6711 brachytherapy seeds for comparison. Absorbed
      dose within the tumor volume was calculated for AgTPPS4 concentrations ranging
      between 0 and 20 mmol/kg tumor weight. These theoretical studies demonstrated
      linear increases in dose absorbed by the tumor with corresponding increases in
      AgTPPS4 concentration. The required AgTPPS4 concentration (RSC) to achieve at
      least a ten percent absorbed dose increase is approximately 6.5 mmol/kg tumor
      weight for model 6702 seeds. In vivo biodistribution and in vitro toxicity
      studies were conducted to determine if the theoretically derived RSC could be
      achieved biologically. Cell toxicity studies showed that TPPS4 porphyrin
      derivatives were cytotoxic at concentrations required to provide significant
      brachytherapy dose enhancement. Reverse phase HPLC confirmed that toxicity was
      due to intrinsic properties of the TPPS4 molecule, not the presence of free
      silver, drug impurities, or metabolites. Further research is necessary to develop
      a nontoxic molecular carrier for delivering silver to the DNA of tumor cells.

PMID- 9608483
TI  - Evaluation of a new sealed reentrant well chamber for HDR and LDR brachytherapy
      calibrations.
AB  - A new reentrant ionization chamber SNC 1008 has been introduced for low dose rate
      (LDR) and high dose rate (HDR) brachytherapy source calibrations. There is no air
      density correction requirement for the chamber since it is hermetically sealed.
      In this study we evaluate its use for HDR as well as LDR source calibrations. The
      magnitude of the ionization current collected was found to be independent of the
      sign of the polarizing voltage within +/- 0.5%. The axial response curve of the
      well chamber reveals a "plateau region" (+/- 0.5% dose variation) of 4.2 cm,
      which is larger than the published values for other commercially available
      chambers. Long-term stability of the chamber was evaluated. Short-term response
      and source positioning reproducibility were tested using both LDR and HDR
      sources. Ion collection efficiency was found to be high, making the chamber
      suitable for HDR 192Ir sources.

PMID- 9608484
TI  - Analytical approach to heterogeneity correction factor calculation for
      brachytherapy.
AB  - In brachytherapy treatment planning, the effects of tissue and applicator
      heterogeneities are commonly neglected due to lack of accurate, general, and fast
      three-dimensional (3D) dose-computational algorithms. A novel approach, based on
      analytical calculation of scattered photon fluxes inside and around a disk-shaped
      heterogeneity, has been developed for use in the three-dimensional scatter
      subtraction algorithm. Specifically, our model predicts the central-ray dose
      distribution for a collimated photon isotropic source or brachytherapy "minibeam"
      in the presence of a slab of heterogeneous material. The model accounts for the
      lateral dimensions, location, composition, density, and thickness of the
      heterogeneity using precalculated scatter-to-primary ratios (SPRs) for the
      corresponding homogeneous problem. The model is applicable to the entire
      brachytherapy energy range (25 to 662 keV) and to a broad range of materials
      having atomic numbers of 13 to 82, densities of 2.7 g.cm-3 (Al) to 21.45 g.cm-3
      (Pt) and thicknesses up to 1 mean free path. For this range of heterogeneous
      materials, the heterogeneity correction factors (HCFs) vary from 0.09 to 0.75.
      The model underestimates HCF when multiple scattering prevails and overestimates
      HCF when absorption dominates. However, the analytic model agrees with Monte
      Carlo photon transport (MCPT) benchmark calculations within 1.8% to 10% for 125I,
      169Yb, 192Ir, and 137Cs for a wide variety of materials, with the exception of
      Ag. For 125I shielded by Ag, where the mean discrepancy can exceed 25%, the error
      is due to K-edge characteristic x rays originating within the heterogeneity. The
      proposed approach provides reductions in CPU time required of 5 x 10(4)-10(5) and
      100 in comparison with direct MCPT simulation and 1D numerical integration,
      respectively. The limitations of model applicability, as determined by the
      physical properties of heterogeneity material and accuracy required, are also
      discussed.

PMID- 9608485
TI  - Experimental and Monte Carlo dosimetry of the Henschke applicator for high dose
      rate 192Ir remote afterloading.
AB  - We have performed extensive computational and experimental dosimetry of the
      Henschke applicator with respect to high dose-rate 192Ir brachytherapy using a
      GAMMAMED remote afterloader. Our goal was to generate clinically useful two- and
      three-dimensional look-up tables. Dose measurements of the Henschke applicator
      involved using TLD chips placed in a polystyrene phantom. Monte Carlo simulations
      were performed using the MCNP code. The computational models included the
      detailed geometry of 192Ir source, tandem tube, and shielded ovoid. The measured
      dose rates were corrected for the dependence of TLD sensitivity on the distance
      of measurement points from the source. Transit dose delivered during source
      extension to and retraction from a given dwell position was estimated by Monte
      Carlo simulations, and a correction was applied to the experimental values. For
      the applicator tandem, the ratio of dose rates obtained by MCNP to those measured
      by TLD chips ranges from 0.92 to 1.10 with an average of 0.98 and a standard
      deviation of 0.02. The measured and calculated dose rates at 1 cm on the
      transverse axis are 1.10 cGy U-1 h-1. For the shielded ovoid, the ratio ranges
      from 0.88 to 1.16 with an average of 1.00 and a standard deviation of 0.07.
      Causes of the discrepancy between the Monte Carlo and TLD results were
      identified. We found that the combined uncertainty of measured dose rates due to
      these causes is 5.6% for the applicator tandem and 8.4% for the shielded ovoid.
      Therefore, the results of the Monte Carlo simulation are considered to have been
      validated by the measurements within the uncertainty involved in the calculation
      and measurements.

PMID- 9608486
TI  - A method to improve the effectiveness of diode in vivo dosimetry.
AB  - A routine diode in vivo dosimetry program based on a combination of entrance and
      exit dose measurements was clinically implemented in the radiation oncology
      department of Grace Hospital, Detroit, in January 1995. The delivered dose has
      been monitored by taking weekly measurements. The calibration of the diodes and
      the in vivo dosimetry protocol for this new, more effective type of dose
      verification is presented. The problems encountered within the program are
      discussed along with our solutions.

PMID- 9608487
TI  - Verification of the correspondence between CT-stimulated and treatment beams.
AB  - A single phantom technique has been developed to verify the full CT simulation
      and treatment-beam delivery procedures. The phantom consists of a target
      delineated by thin copper strips, affixed to therapy verification film, and
      inserted securely between two slices of water-equivalent material. The target is
      defined with the aid of the copper strips, and the position of the isocenter and
      beam parameters such as field size, and gantry and collimator angle are
      determined by CT simulation. With these parameters, the phantom is subsequently
      irradiated by the linear accelerator in the treatment position. Correspondence
      between the planned and the irradiated region is determined by the position of
      the copper strips on the film. The technique is a simple and practical method for
      verifying the entire CT simulation and treatment-beam delivery processes, and
      provides a permanent record of the correspondence between the planning digitally
      reconstructed radiographs (DRR) and the actual beam delivered.

PMID- 9608488
TI  - Extraction of the photon spectra from measured beam parameters.
AB  - Knowledge of the photon spectrum of a radiotherapy beam is often needed for three
      dimensional (3-D) dose calculations using Monte Carlo methods and/or algorithms
      employing energy deposition kernels. Direct measurement of the x-ray energy
      fluence spectrum is not feasible for the high-energy photon beams used
      clinically. In this paper, the spectrum is extracted from basic beam data that
      are readily obtained for a clinical beam. We describe the photon spectrum using
      just two parameters. One parameter, which determines the high-energy part of the
      spectrum, is obtained using the measured dose in the buildup region for a small
      field, where electron contamination of the beam can be neglected. The other
      parameter is extracted from the photon beam attenuation in water. The results
      compare favorably to spectra generated from Monte Carlo simulations.

PMID- 9608489
TI  - On the calculation of mean restricted collision stopping powers.
AB  - An analytical method for the calculation of ratios of mean restricted collision
      stopping powers (L/rho)(g)m averaged over the charged particle spectra and the
      photon spectrum that is accurate to first order has been developed, and it has
      been explored whether a moderate change in the photon fluence spectrum with field
      size has an effect on the mean restricted collision stopping power ratio in high
      Z materials. The results of this study indicate that for the case of a
      miniphantom, moderate changes in the photon fluence spectrum have only a weak
      effect on the ratios of mean restricted collision stopping powers.

PMID- 9608490
TI  - A double mirror W/C multilayer monochromator for radiation biology applications.
AB  - A double-mirror multilayer monochromator was developed for the purpose of
      irradiating live cell cultures at the Synchrotron Radiation Center, University of
      Wisconsin-Madison. The monochromator is designed for the soft x-ray region with
      photon energies between 270 and 2400 eV. Multilayer mirrors with 55 bilayers of
      W/C and a bilayer spacing of d = 3.0 nm are sputter deposited on Si substrates.
      By proper masking of the sputtering sources, variation in the bilayer spacing
      over the area of the mirror is minimized. The uniformity of the bilayer spacing
      was measured to be delta d/d < 1%, over the 75 mm x 25 mm area of the mirrors.
      The reflectivity was measured as a function of energy to determine the integrated
      reflectivity and evaluate the contribution of the specular reflection and higher
      orders to the monochromatic beam. The use of suitable filters with a Si(Li)
      detector allows determination of the spectral output of the monochromator. The
      output power of the monochromator between 270 and 2400 eV is measured. The
      resolution of the monochromator is delta lambda/lambda = 0.04. Applications of
      the monochromator to radiation biology are discussed.

PMID- 9608491
TI  - Effective dose in diagnostic radiology as a function of x-ray beam filtration for
      a constant exit dose and constant film density.
AB  - Individual organ absorbed dose and total effective dose for nine common
      radiographic projections were investigated as a function of half-value-layer,
      HVL, and total equivalent filtration for the following cases: (1) with the
      patient exit dose held constant and (2) with the film density held constant. As
      expected, the absorbed dose to organs proximal to the x-ray beam entry point
      tracked with skin dose as a function of HVL, whereas organ dose distal to the x
      ray beam entry point was almost independent of HVL. Dose to organs near mid-line
      showed an intermediate HVL dependence. For the nine radiographic projections,
      increasing the total filtration from 1.5 to 4.0 mm Al while holding the kVp fixed
      resulted in mean decreases in the effective dose of 17% for the case of a
      constant exit dose, and 25% for a constant film density with a "400 speed" rare
      earth screen-film system. The decreases in the mean skin entrance doses were 38%
      and 45%, respectively. With the screen-film system, the average effective dose
      decreased at 16% per mm of added Al between 1.5 and 2.5 mm Al total filtration,
      and at 7% per mm between 2.5 and 4.0 mm. These results partially support the NCRP
      Report No. 102 recommendation that the minimum filtration be 2.5 mm Al for
      general diagnostic x-ray tubes. They also suggest, using the linear no-threshold
      radiation risk model, that further significant reductions in stochastic risk to
      the U.S. population can be achieved by raising the minimum beyond 2.5 mm.
      Experience over a 12 year period in our tertiary care teaching hospital indicates
      that adding 1-1.5 mm Al filtration beyond the 2.5 mm minimum does not pose a
      problem in terms of additional tube loading or reduction in image quality.
      However, these issues need to be more formally addressed.

PMID- 9608492
TI  - There is no mechanistic basis for the use of the linear-quadratic expression in
      cellular survival analysis.

PMID- 9608493
TI  - Comments on "Quantitative evaluation of radiochromic film response for two
      dimensional dosimetry" [Med. Phys. 24, 223-231 (1997)].

PMID- 9608494
TI  - [Invasive fungal infections in patients with blood disorders].
AB  - BACKGROUND: Invasive fungal infections (IFI) are severe infectious complications
      frequently observed in patients with hematological disorders. The aims of this
      study were to analyse the characteristics of this particular type of infection in
      a large series of a single institution and to determine the factors associated
      with the outcome and therapeutic response. PATIENTS AND METHODS: This study
      reviews the clinical and microbiological features of 155 IFI occurred among 144
      patients with hematologic disorders throughout a period of 17 years in a single
      institution. RESULTS: In 118 cases (82%) the diagnosis was acute leukemia. The
      main risk factors for developing IFI included a persistent and profound
      granulocytopenia, the use of broad-spectrum antibacterial agents, indwelling
      central venous catheters and the damage of normal host barriers following
      intensive cytotoxic chemotherapy. Candida (65 cases [44%]) and Aspergillus (38
      cases [26%]) species were the most common fungal species isolated. An increasing
      number of IFI were caused by fungi previously considered as contaminants or
      harmless colonizers. The outcome of IFI was favourable in 78 cases (50%). The
      most important prognostic factors for the outcome of the IFI were the phase of
      cytotoxic chemotherapy (p = 0.005), the response of the underlying disease to the
      cytotoxic chemotherapy (p < 0.00001), and the recovery of neutropenia during the
      infection course (p < 0.00001). An earlier use of empirical antifungal therapy
      was also associated with a better outcome. CONCLUSIONS: In spite of earlier
      treatment and regardless the development of new antifungal agents, the prognosis
      of IFI in patients with hematological malignancies remains poor. The use of
      hematopoietic growth factors, through their impact in the duration and severity
      of neutropenia, may prove valuable the management of IFI in this setting.

PMID- 9608495
TI  - [Invasive fungal infections in liver transplant recipients: analysis of 21
      cases].
AB  - BACKGROUND: Invasive fungal infections (IFI) are one of the most important causes
      of mortality in liver transplant (LT) recipients. The aim of this study was to
      describe the characteristics of IFI in the LT program of our institution with an
      special emphasis in the differences between Candida infections (CI) and that
      caused by other fungi (NCI). PATIENTS AND METHODS: Retrospective analysis of the
      hospital charts of 21 patients who underwent a LT from February 1987 to December
      1995. The diagnosis of IFI required the histological evidence of tissue invasion
      or a positive culture in a tissue sample or in an usually sterile fluid.
      Esophageal candidiasis was not considered as IFI. Antifungal prophylaxis was
      performed either with nystatin or fluconazole. RESULTS: Twenty-one of 356
      patients (6%) developed a total of 23 episodes of IFI. Pathogens were Candida
      spp. (n = 10), Aspergillus (n = 8), Zygomicetes (n = 4) and Cryptococcus (n = 1).
      Fifty-seven percent of the episodes of IFI (80% of those caused by Candida and
      38% of those produced by other fungi; p < 0.05) developed in the first 3 months
      after transplantation and only 5 episodes appeared after the sixth month. The
      diagnosis of IFI was done at autopsy in 6 patients (29%). Overall, NCI (13
      episodes) predominated over CI (10 episodes), being the later the cause of the
      54% of the episodes in the first 178 recipients but only the 30% in the last 178
      patients (p = 0.09). No differences were found in the distribution of the risk
      factors amongst those patients with CI or NCI. Seventeen of the 21 patients (71%)
      died and 15 of these deaths (72%) were attributable to fungi; 15 patients who
      died either did not receive amphotericin (n = 6) or received a cumulative dose
      lower than 500 mg. Six patients received a cumulative dose of more than 1.5 g
      (mean, 3.2 g) and four of them were cured. Mortality in the nonfungal infection
      group was 26% (p < 0.001). CONCLUSIONS: IFI was a rare but severe complication in
      our LT recipients. The relative frequency of CI was progressively decreasing
      during the study period, being NCI the predominant infections. Amphotericin
      therapy was effective only when a high cumulative dose could be administered.

PMID- 9608496
TI  - [Calcitonin prescriptions: an estimate of the expenditure due to inadequate
      prescription].
AB  - BACKGROUND: The use of calcitonin is very common in patients diagnosed with
      osteoporosis. The objective of this study was to determine the percentage of
      adequate prescriptions of calcitonin for patients with osteoporosis and to
      estimate the costs due to inadequate prescription. PATIENTS AND METHODS:
      Observational study. Four pharmacies in Osona County (Barcelona) were randomly
      selected. During two time periods, July-September and November-December of 1994,
      all women filling prescriptions for calcitonin in any of the eight pharmacies
      were invited to participate in the study. Adequate and inadequate prescription of
      calcitonin was determined based on the patient's clinical record. Justifiable and
      non-justifiable prescriptions were then determined after implementing a protocol
      and reviewing X-rays of the spine. RESULTS: Forty-eight women agreed to
      participate (participation rate: 68%). In the first analysis, 58.3% (95% CI: 43
      72) of prescriptions were determined to be inadequate whereas in the second
      analysis 29.2% (95% CI: 17-44) were considered non-justifiable. Chronic back pain
      was associated with non-justifiable prescription of calcitonin (odds ratio: 5.2;
      95% CI: 1.3-33.4). In the best of situations, the excess in annual spending due
      to inadequate prescription was estimated at 13 million pesetas for Osona County,
      1,300 million for Catalonia, and 4,300 million for Spain. CONCLUSIONS: Between
      one-third and one-half of patients prescribed calcitonin in the study area
      apparently do not need it. Many cases of chronic back pain are being treated as
      osteoporosis without being properly studied. The costs derived from this
      incorrect practice are important. This study highlights the need for better
      practices in the diagnosis of osteoporosis.

PMID- 9608498
TI  - [Reflections on obstructive apnea sleep syndrome].

PMID- 9608497
TI  - [Invasive fungal infections].

PMID- 9608499
TI  - [Invasive pulmonary aspergillosis: a study of 33 cases].
AB  - Invasive pulmonary aspergillosis (IPA) is an infectious complication appearing
      mainly in immunosuppressed patients, whose diagnosis is often difficult and
      lately made, and that usually bears a dismal prognosis. Patients diagnosed as
      having IPA from 1989 to 1994 were retrospectively analyzed. Probable IPA was
      diagnosed on the basis of a positive culture for Aspergillus together with a
      consistent radiological image. Confirmed IPA was diagnosed if there was, in
      addition to the former, a pathological examination showing Aspergillus hifae
      invading pulmonary parenchyma and/or pulmonary vessels. There were 25 men and 8
      women with a mean age of 53.7 +/- 16.9 years (range: 22-86 years). IPA was
      confirmed in 11 cases and probable in 22. Sixty three percent of the patients had
      hematologic malignancy or solid cancer, whereas 30.3% did not have prior
      granulocytopenia or immunosuppressive therapy. The mean (SD) interval between
      admission and diagnosis was 40.2 (37.1) days (range: 1-180 days), and the
      diagnosis was made while the patient was still alive in 75% of the cases. Fifteen
      percent of the patients had extrapulmonary aspergillosis. The most frequent
      finding both on X-ray film of the chest and pulmonary computed tomography were
      bilateral multiple pulmonary nodules. Thirteen patients were treated with
      itraconazole, 6 with amphotericin B, 5 received both drugs, and 2 received
      fluconazole. Nineteen patients (57.6%) died and the case-fatality rate among
      treated patients was 46.1%. IPA presents mainly in immunosuppressed patients, but
      there was a not negligible proportion of patients lacking the classical risk
      factors. IPA is often a lately made diagnosis and in a quarter of the patients it
      is not made when the patient is alive. The most frequent radiological
      presentation are multiple bilateral nodules. The case-fatality rate of IPA is
      exceedingly high, even when if the patient has been adequately treated.

PMID- 9608500
TI  - [Carnitine deficiency: clinical significance].

PMID- 9608501
TI  - [Necrotizing infections of soft tissues. Multidisciplinary perspective].

PMID- 9608502
TI  - [Acute pancreatitis due to carbamazepine in a patients with AIDS].

PMID- 9608503
TI  - [Hashimoto encephalopathy].

PMID- 9608504
TI  - [A proposal to define the endemic zone of Lyme borreliosis].

PMID- 9608505
TI  - [Anaphylaxis due to glucocorticoids].

PMID- 9608506
TI  - [Breast cancer mortality in Castilla-La Mancha (1975-1990)].

PMID- 9608507
TI  - Use of FLP/FRT system to study Drosophila development.
AB  - Marked clones in mosaic animals have been used extensively to answer
      developmental questions in Drosophila. Recently, the use of the FLP/FRT system
      has allowed for the high-frequency production of mosaic animals for 95% of
      Drosophila genes. Cell markers have been engineered in this system to label
      mutant clones in both developing tissues and adult cuticle. Strains carrying
      these genetically marked FLP/FRT chromosomes have greatly enhanced our ability to
      study gene function in both germline and somatic Drosophila cells.

PMID- 9608508
TI  - Ectopic gene expression in Drosophila using GAL4 system.
AB  - Expressing a gene in cells in which it is not normally active is a powerful way
      of determining its function. The GAL4 system allows the selective expression of
      any cloned gene in a wide variety of cell- and tissue-specific patterns in
      Drosophila. A promoter (or enhancer) directs expression of the yeast
      transcriptional activator GAL4 in a particular pattern, and GAL4 in turn directs
      transcription of the GAL4-responsive (UAS) target gene in an identical pattern.
      The system's key feature is that the GAL4 gene and UAS-target gene are initially
      separated into two distinct transgenic lines. In the GAL4 line, the activator
      protein is present, but has no target gene to activate. In the UAS-target gene
      line, the target gene is silent because the activator is absent. It is only when
      the GAL4 line is crossed to the UAS-target gene line that the target gene is
      turned on in the progeny. In this article we describe, in detail, how to generate
      and characterize GAL4 lines and how to prepare UAS-target gene lines. Vector maps
      are provided for pGaTB, P[GawB], and pP[UAST]. In addition, we consider the range
      of UAS-reporters currently available and review several new modifications of the
      GAL4 system.

PMID- 9608509
TI  - Inducible gene targeting in mice using the Cre/lox system.
AB  - Molecular techniques now allow the design of precise genetic modifications in the
      mouse. Not only can defined nucleotide changes be engineered into the genome of
      the mouse, but genetic switches can be designed to target expression or ablation
      of any gene (for which basic molecular information is available) to any tissue at
      any defined time. These strategies promise to contribute substantially to an
      increased understanding of individual gene function in development and
      pathogenesis. A powerful tool, both for the design of such genetic switches and
      for speeding the creation of gene-modified animals, is the Cre site-specific DNA
      recombinase of bacteriophage P1. Precise DNA rearrangements and genetic switches
      can be efficiently generated in a straightforward manner using Cre recombinase.
      In conjunction with inducible systems for controlling Cre expression and
      function, these recombination-based strategies are likely to have a profound
      impact on developmental biology and the generation of useful animal models of
      human disease.

PMID- 9608510
TI  - Lineage analysis using retroviral vectors.
AB  - Knowledge of the genealogical relationships of cells during development can allow
      one to gain insight into when and where developmental decisions are being made.
      Genealogical relationships can be revealed by a variety of methods, all of which
      involve marking a progenitor cell and/or a group of cells and then following the
      progeny. The use of replication-incompetent retroviral vectors for the analysis
      of lineal relationships in developing vertebrate tissues is described. An
      overview of the relevant aspects of the retroviral life cycle is given, and the
      strategies and current methods in use in our laboratory are described.

PMID- 9608511
TI  - Targeted gene misexpression in chick limb buds using avian replication-competent
      retroviruses.
AB  - The methods and applications for using avian replication-competent retroviruses
      to target gene misexpression in the developing limb bud of the chicken are
      described. These viruses provide the means to exploit the strengths of the chick
      as a model system in experimental embryology in conjunction with a genetic
      approach for ectopically expressing a gene of interest. The applications and
      strengths of the system are detailed. All the steps required to produce a virus
      carrying a transgene of interest and the methodologies behind designing and
      carrying out misexpression strategies are outlined, and some useful techniques
      for analyzing infected embryos are described.

PMID- 9608513
TI  - [Environmental microbiology in Latin America].

PMID- 9608512
TI  - Controlling gene expression using synthetic ligands.
AB  - Chemical inducers of dimerization (dimerizers) are a new class of reagents used
      for controlling protein-protein interactions. Use of a small-molecule, cell
      permeable dimerizer to control the interaction of a transcription activation
      domain and a DNA-binding domain allows the level of expression of a target gene
      to be regulated by the concentration of dimerizer. The modular design of
      components has facilitated the development of multiple systems that can be used
      to readily generate cell lines in which basal expression of the target gene is
      low and induced to high levels by a nontoxic dimerizer. The development and use
      of one such system to control the expression of a gene in cultured cells are
      described.

PMID- 9608514
TI  - Trends in wine microbiology.
AB  - During the last few years many winemakers have started to use pure Saccharomyces
      cerevisiae strains, frequently isolated from their own geographical regions, to
      produce wines of more reproductable quality. This microbiological simplification
      has opened the way for the genetic modification of wine yeast strains. This
      review concerns the application of molecular techniques in oenology, not only
      from the point of view of the construction of recombinant strains but also for
      the study of the population dynamics of wine fermentations.

PMID- 9608516
TI  - Biology and applications of mycorrhizal fungi.
AB  - Mycorrhizae have been shown to increase growth and yield of plants. They have
      been identified with both nutrient mobilization and nutrient cycling. Arbuscular
      (or endo-) mycorrhizae play a significant role in agriculture and most natural
      ecosystems, whereas ectomycorrhizae have a great potential in forestry and
      wasteland regeneration. The use of mycorrhizal fungi would reduce dependence on
      chemical fertilizers besides minimizing environmental pollution. The present
      review addresses the progress that there has been in the area of the ecto- and
      endomycorrhizae. It also examines the potential of field applications of
      mycorrhizal biotechnology in agriculture and forestry.

PMID- 9608515
TI  - Microbiological quality of natural waters.
AB  - Several aspects of the microbiological quality of natural waters, especially
      recreational waters, have been reviewed. The importance of the water as a vehicle
      and/or a reservoir of human pathogenic microorganisms is also discussed. In
      addition, the concepts, types and techniques of microbial indicator and index
      microorganisms are established. The most important differences between faecal
      streptococci and enterococci have been discussed, defining the concept and
      species included. In addition, we have revised the main alternative indicators
      used to measure the water quality.

PMID- 9608517
TI  - Selenite bioremediation potential of indigenous microorganisms from industrial
      activated sludge.
AB  - Ten bacterial strains were isolated from the activated sludge waste treatment
      system (BIOX) at the Exxon refinery in Benicia, California. Half of these
      isolates could be grown in minimal medium. When tested for selenite
      detoxification capability, these five isolates (members of the genera Bacillus,
      Pseudomonas, Enterobacter and Aeromonas), were capable of detoxifying selenite
      with kinetics similar to those of a well characterized Bacillus subtilis strain
      (168 Trp+) studied previously. The selenite detoxification phenotype of the Exxon
      isolates was stable to repeated transfer on culture media which did not contain
      selenium. Microorganisms isolated from the Exxon BIOX reactor were capable of
      detoxifying selenite. Treatability studies using the whole BIOX microbial
      community were also carried out to evaluate substrates for their ability to
      support growth and selenite bioremediation. Under the appropriate conditions,
      indigenous microbial communities are capable of remediating selenite in situ.

PMID- 9608518
TI  - Sorption of metals by Chlorobium spp.
AB  - The capacity of two species of green phototrophic sulfur bacteria, Chlorobium
      limicola and C. phaeobacteroides, to sorb several metal ions (Mn2+, Fe2+, Ni2+,
      Cu2+, Zn2+, Cd2+ and Pb2+) has been tested in laboratory batch cultures at
      increasing concentrations up to 2,000 mumol/l. Except for nickel--which was not
      sorbed to bacterial cells--the rest of metals tested were bound in a fast and
      passive process, which was mathematically described by means of Freundlich
      isotherms models. The sorption capacity of the two species studied were found to
      be dependent on the metal involved, whereas no differences were observed in the
      sorption intensity, suggesting that in all cases the sorption process proceeds in
      a similar way. Further, the comparison of the sorption intensity values as well
      as the metal recovery index (Ri), for both species, revealed that C.
      phaeobacteroides was more efficient that C. limicola to attach metal ions. The
      ecological significance of this ability in the water column of some stratified
      lakes, where coinciding maxima of ferrous iron and green photosynthetic sulfur
      bacteria are frequently found, is discussed.

PMID- 9608519
TI  - Gram-positive bacteria of marine origin: a numerical taxonomic study on
      Mediterranean isolates.
AB  - A numerical taxonomic study was performed on 65 Gram-positive wild strains of
      heterotrophic, aerobic, marine bacteria, and 9 reference strains. The isolates
      were obtained from oysters and seawater sampled monthly over one year, by direct
      plating on Marine Agar. The strains were characterized by 96 morphological,
      biochemical, physiological and nutritional tests. Clustering yielded 13 phena at
      0.62 similarity level (Sl coefficient). Only one of the seven phena containing
      wild isolates could be identified (Bacillus marinus). A pronounced salt
      requirement was found in most isolates.

PMID- 9608520
TI  - Coliforms and Salmonella in seawater near to domestic sewage sources in Fortaleza
      (Ceara, Brazil).
AB  - The bacteriological conditions of the coastal region of Fortaleza (Ceara,
      Brasil), including the coastal zones of the Ceara and Coco rivers, were examined.
      The study was conducted during June, September and December 1993, and March 1994.
      The region was divided into two areas: (i) Direct Influence Area (DIA),
      consisting of 20 sampling stations located near to discharge zones of the
      submarine pipeline system, where collections were carried out at the surface, and
      (ii) Indirect Influence Area (IIA), located near to the coastal zone, including
      Barra do Ceara, Kartodromo, Volta de Jurema, Mucuripe, Farol and Caca e Pesca
      beaches, totalling 26 sampling stations. The most probable number (MPN) of both
      total and fecal coliforms in DIA was positive only in station number 6, near to
      the sewage discharge exit. The following bacteria were identified: Citrobacter
      sp., Enterobacter aerogenes and Escherichia coli. Kartodromo beach was
      contaminated throughout the sampling period. Results of total fecal MPN was
      essentially lower than 3.0 x 10(2) coliforms/100 ml at Caca e Pesca beach. In
      December, at both DIA and IIA, Salmonella was identified in several samples. In
      DIA, the spatial distribution for Salmonella suggests that there should be a
      coastal sea current from east to west along the coastline. In IIA, Salmonella was
      identified at Kartodromo and Farol beaches throughout the sampling period.

PMID- 9608521
TI  - Usefulness of phage typing and "two-way ribotyping" to differentiate Salmonella
      enteritidis strains.
AB  - The capacity to differentiate Salmonella enteritidis strains by phage typing and
      "two-way ribotyping" performed with PstI and SphI was evaluated. The typeability
      was 96.8% in phage typing and 100% in ribotyping. The series was differentiated
      into 13 phage types, 19 combined ribotypes, and 39 subtypes or clonal lines by
      combining results from both methods (of which 11, 13, and 35, respectively, were
      represented by natural strains). Ribotyping differentiated strains ascribed to
      PTs 1, 4, 6a, 7, 8, RDNC and UPT. Conversely, some strains of PTs 1, 4, 5a, 6,
      6a, 7, 34, RDNC and UPT fall into the most frequent combined ribotype. A
      dendrogram of genetic similarity generated from the combined ribotypes was
      traced, and, at a 0.82 similarity level, it showed a major cluster (including 17
      combined ribotypes, 88.4% strains ascribed to all PTs tested except PT11), a
      minor cluster, and four additional lines more loosely related.

PMID- 9608522
TI  - Distribution of the trehalase activation response and the regulatory trehalase
      gene among yeast species.
AB  - In Saccharomyces cerevisiae and other yeasts the activity of regulatory
      trehalases increases in response to the addition of glucose and to thermal
      changes in the extracellular medium. We have performed an screening on the extent
      of this response among different representative yeast species and the results
      show that this ability is displayed only by a few members of the
      Saccharomycetaceae family. However, all yeasts examined contain a gene related to
      that coding for regulatory trehalase in S. cerevisiae. This finding reveals that
      the operational distinction between regulatory and nonregulatory trehalase in
      yeasts is not a property of the enzyme by itself but relays on the expression of
      accompanying mechanisms able to modulate trehalase activity.

PMID- 9608523
TI  - Comparison between the polypeptide profile of halophilic bacteria and salt
      tolerant plants.
AB  - Changes in the polypeptide profile induced by salt stress in halotolerant and
      halophilic bacteria, isolated from the Atacama desert (northern Chile), were
      compared with those in the cotyledons of Prosopis chilensis (Leguminoseae)
      seedlings, a salt tolerant plant. SDS-PAGE analyses show the presence of four
      predominant polypeptides, with molecular weights around 78, 70, 60 and 44 kDa
      respectively, both in bacteria and in cotyledons from P. chilensis seedlings
      raised under salt stress conditions. Moreover, the 60 and 44 kDa polypeptides
      seem to be salt responsive, since their concentration increases with increasing
      NaCl in the growth medium. Our results suggest a common mechanism for salt
      tolerance in prokaryotes and in eukaryotes.

PMID- 9608524
TI  - Development of a selective culture medium for Fusarium moniliforme.
AB  - Nash and Snyder medium and malachite green agar 2.5 ppm medium, a new selective
      culture medium designed in our laboratory, were challenged with pure cultures of
      Fusarium moniliforme strains and two different mixed-conidium suspensions, which
      included rapidly spreading fungi, for their utility in the isolation and
      enumeration of F. moniliforme. From the results of this comparative study,
      malachite green agar 2.5 ppm allowed only the selective growth of F. moniliforme
      whereas Nash and Snyder medium allowed both the growth of F. moniliforme and
      other species not belonging to Fusarium spp. The enumeration of F. moniliforme
      propagules was similar in both culture media.

PMID- 9608525
TI  - European journals on microbiology.
AB  - A survey on the scientific journals dealing with microbiology published in Europe
      has been carried out. Eighteen European countries publish microbiological
      journals with the United Kingdom. Netherlands and Germany leading in number of
      journals on this specialty. Most of the European journals on microbiology are
      published bimonthly (27%), and English is the most common language used (54%).
      Most of these journals (86%) are included in some database, but only 36 (25%) are
      indexed in the six databases studied. Out of the 146 journals registered, 71
      (49%), published in 11 European countries, are included in the 1995 Journal
      Citation Reports (ISI, Philadelphia).

PMID- 9608526
TI  - [4 years of Microbiologia SEM (1994-1997)].
AB  - Different aspects of Microbiologia SEM editorial process over the years 1994-1997
      are analyzed: number of originals received, the process leading to their
      publication, rates of accepted and refused papers, time needed for each step of
      the editorial process--which comprises scientific, language editing, if needed--,
      as well as some characteristics that can define the patterns of the articles,
      such as number of authors, institutions where the authors work and mean number of
      references. The contents of the different sections (editorial, research and
      review articles, perspectives, opinion, books review) are commented on, as well
      as the role played by some of them as forums for the discussion of topics of
      current scientific interest, especially the editorials focusing on the state-of
      the-art of microbiological research in Latin American countries. Characteristics
      and frequency of monographic issues are also presented. The information is
      complemented with data about the circulation and distribution of the journal, its
      inclusion in international indexes and its current electronic publication on the
      world wide web.

PMID- 9608527
TI  - [1 year of Microbiologia SEM on the Internet].

PMID- 9608528
TI  - Neurotrophins rapidly modulate growth cone response to the axon guidance
      molecule, collapsin-1.
AB  - We show that neurotrophins acting at the growth cone via Trk receptors can
      mediate rapid and distinct changes in growth cone response to collapsin-1, an
      inhibitory axon guidance molecule. We find that the sensitivity of growth cones
      of dorsal root ganglia (DRG) neurons to collapsin-1 differs when chronically
      cultured in BDNF, NT-3, or NGF with those in BDNF most sensitive and those in NGF
      least sensitive. Further, growth cones chronically cultured in BDNF rapidly
      decrease their sensitivity to collapsin-1 with acute exposure to NGF. Conversely,
      growth cones chronically cultured in NGF rapidly increase their sensitivity to
      collapsin-1 with acute exposure to BDNF. These bidirectional effects of
      neurotrophins appear to be mediated by the neurotrophin-specific Trk receptors on
      the growth cones since most growth cones are immunopositive for TrkA and TrkB,
      the NGF and BDNF receptors, respectively, and k252a, a selective inhibitor of Trk
      mediated responses to neurotrophins, diminishes collapsin-1-induced growth cone
      collapse. These findings indicate that the response of growth cones to axon
      guidance molecules is dynamic and can be rapidly and differentially modulated by
      neurotrophins.

PMID- 9608529
TI  - Differentiative effects of dopamine on striatal neurons involve stimulation of
      the cAMP/PKA pathway.
AB  - The neurotransmitter dopamine (DA) stimulates neurite outgrowth and growth cone
      formation in cultures of embryonic rat striatum through activation of D1 but not
      D2 receptors. We show here that neurite outgrowth could be stimulated to a
      similar extent by elevating cellular cAMP levels. Second, the neuritotrophic
      effect of DA was completely abolished by inhibiting adenylate cyclase or protein
      kinase A (PKA) but not protein kinase C (PKC). Third, double staining of cultures
      with antibodies against growth-associated protein-43 (GAP-43) and the
      phosphorylated form of the cAMP response element binding protein (pCREB) showed
      that pCREB was nearly exclusively associated with GAP-43-positive, i.e., actively
      growing, neurons. Again, this effect depended on D1 receptor and PKA activation.
      Although cross-talk with other signaling pathways needs to be studied further, we
      conclude that DA promotes the differentiation of striatal neurons via stimulation
      of D1 receptors and the cAMP/PKA signal transduction pathway.

PMID- 9608530
TI  - Sympathetic neuron survival and proliferation are prolonged by loss of p53 and
      neurofibromin.
AB  - The proteins encoded by the p53 and Nf1 tumor suppressor genes are involved in
      cell signaling and regulation of proliferation during normal development and
      differentiation, as well as during tumor progression. To characterize the roles
      of these genes in the proliferation and survival of embryonic neurons, we have
      used dissociated cultures of sympathetic superior cervical ganglia (SCG) isolated
      from p53 and Nf1 single and compound-mutant mouse embryos. We have defined a
      temporal window for p53 involvement in sympathetic neuron survival and
      proliferation. Moreover, our results indicate that cooperativity between
      mutations in Nf1 and p53 prolongs SCG neuron proliferation and increases the
      incidence of neural tube defects in compound-mutant embryos.

PMID- 9608531
TI  - The DUTT1 gene, a novel NCAM family member is expressed in developing murine
      neural tissues and has an unusually broad pattern of expression.
AB  - A new member of the NCAM family mapping to 3p12 has been isolated and predicted
      to be arranged in five immunoglobulin-like domains and three fibronectin-like
      domains which are particularly homologous to L1. There is a transmembrane domain
      and a long cytoplasmic region with no detectable homology to other sequences.
      Although less closely related to DCC, another family member, both share a loop of
      positively charged amino acids within the first immunoglobulin domain, unique to
      these two members of this very large gene family. Preliminary studies of
      expression in mouse embryos support an inferred role in neural development, but
      the observation of widespread gene expression in adult human tissues indicates
      that this protein has additional functions to those performed in neural cells.

PMID- 9608532
TI  - Dopamine biosynthesis is selectively abolished in substantia nigra/ventral
      tegmental area but not in hypothalamic neurons in mice with targeted disruption
      of the Nurr1 gene.
AB  - To ascertain the function of an orphan nuclear receptor Nurr1, a transcription
      factor belonging to a large gene family that includes receptors for steroids,
      retinoids, and thyroid hormone, we generated Nurr1-null mice by homologous
      recombination. Mice, heterozygous for a single mutated Nurr1 allele, appear
      normal, whereas mice homozygous for the null allele die within 24 h after birth.
      Dopamine (DA) was absent in the substantia nigra (SN) and ventral tegmental area
      (VTA) of Nurr1-null mice, consistent with absent tyrosine hydroxylase (TH), L
      aromatic amino acid decarboxylase, and other DA neuron markers. TH
      immunoreactivity and mRNA expression in hypothalamic, olfactory, and lower brain
      stem regions were unaffected. L-Dihydroxyphenylalanine treatments, whether given
      to the pregnant dams or to the newborns, failed to rescue the Nurr1-null mice. We
      were unable to discern differences between null and wild-type mice in the
      cellularity, presence of neurons, or axonal projections to the SN and VTA. These
      findings provide evidence for a new mechanism of DA depletion in vivo and suggest
      a unique role for Nurr1 in fetal development and/or postnatal survival.

PMID- 9608533
TI  - Multiple GPI-anchored receptors control GDNF-dependent and independent activation
      of the c-Ret receptor tyrosine kinase.
AB  - Glial cell line-derived neurotrophic factor (GDNF) mediates neuronal survival
      through a receptor complex composed of the c-Retproto-oncogene and GFR alpha-1, a
      member of a family of GPI-anchored receptors. The extent of cross-talk between
      GDNF and GFR alpha receptors and its possible significance for c-Ret activation
      is presently unclear. Using chemical crosslinking we demonstrate here a specific
      interaction between GDNF and GFR alpha-2 expressed in COS cells, albeit of a
      lower affinity than the one between GDNF and GFR alpha-1. In addition, GFR alpha
      2 mediated crosslinking of GDNF of c-Ret as well as ligand-dependent stimulation
      of c-Ret tyrosine phosphorylation. We also describe the isolation of a novel,
      more divergent member of the GFR alpha family, GFR alpha-3, which did not bind
      GDNF directly, but was able to mediate crosslinking of GDNF to c-Ret when both
      receptors were coexpressed in COS cells. Thus, all three GFR alpha receptors
      mediate GDNF binding to c-Ret with efficiencies GFR alpha-1 > GFR alpha-2 > GFR
      alpha-3. c-Ret showed high levels of constitutive tyrosine autophosphorylation
      upon overexpression in COS cells, which was inhibited in a dose-dependent manner
      by coexpression with any of the GFR alpha receptors, suggesting that GFR alpha s
      may also provide a gain control mechanism to increase the signal-to-noise ratio
      of the response to ligand. GFR alpha-2 showed a dynamic pattern of expression in
      rat brain, distinct from that of GFR alpha-1, characterized by high expression in
      cortex, basal forebrain, and specific layers of the olfactory bulb, and low or no
      expression in substantia nigra, cerebellum, and motor nuclei. GFR alpha-2, but
      not GFR alpha-3 mRNA expression was highly induced in several nuclei after
      stimulation with kainic acid. In contrast to GFR alpha-1 and GFR alpha-2, GFR
      alpha-3 expression in postnatal and adult brain was highly restricted.
      Developmentally regulated expression of GFR alpha-3 was, however, detected in
      several peripheral organs and ganglia. Together, these results indicate
      complementary roles for GFR alpha receptors in the regulation of c-Ret activity
      and the maintenance of distinct neuronal circuits in the central and peripheral
      nervous systems.

PMID- 9608535
TI  - The neuregulin precursor proARIA is processed to ARIA after expression on the
      cell surface by a protein kinase C-enhanced mechanism.
AB  - We have investigated how the transmembrane precursor proARIA is processed to ARIA
      (acetylcholine receptor-inducing activity). Pulse-chase labeling in transfected
      Chinese hamster ovary (CHO) cells showed that proARIA was cleaved to release ARIA
      into the medium. Cell surface biotin-labeling experiments demonstrated that
      proARIA was first expressed on the cell surface before being rapidly cleaved to
      release biotin-labeled ARIA into the medium. While not essential for proteolytic
      cleavage of proARIA, serum or phorbol-12-myristate-13-acetate (PMA), which
      activates protein kinase C (PKC), was needed for the efficient release of the
      processed ARIA. Proteolytic cleavage was blocked by brefeldin A, suggesting that
      processing occurred distal to Golgi compartments, and by NH4Cl, suggesting a need
      for intracellular acidic compartments. Serum and PMA also stimulated ARIA release
      from cultured sensory neurons, suggesting that a similar regulated release
      mechanism occurs in neurons and may be important in determining where ARIA is
      released in the developing nervous system.

PMID- 9608536
TI  - Rules for ribozymes.
AB  - The selective inactivation of genes, in a tissue-specific or temporally
      controlled manner, is now an important requirement for the analysis of nervous
      system development and function. Hammerhead ribozymes--catalytic RNA enzymes that
      specifically bind to and then cleave target RNAs--may provide a way to meet this
      requirement, particularly for organisms in which gene inactivation by homologous
      recombination is not feasible. However, ribozyme application has to some extent
      been hampered by limited knowledge as to the base-pairing accessibility of RNA
      target sites in vivo. In an attempt to circumvent this limitation, we have used a
      computer program based on free energy minimization to predict secondary
      structures for 128 RNA sequences for which corresponding ribozymes or antisense
      oligonucleotides have been synthesized, tested, and reported in the literature. A
      comparative analysis of the predicted structures of these targets with the
      reported efficacy of their corresponding antisense reagents has allowed us to
      formulate a set of rules for the rational choice of hammerhead ribozyme flanking
      arms and cleavage sites.

PMID- 9608537
TI  - Molecular basis of allergic diseases.
AB  - This review examines our current understanding of the mechanisms underlying
      allergic diseases. The IgE molecule plays a central role in the pathogenesis of
      immediate hypersensitivity reactions by virtue of its capacity to bind
      specifically to high-affinity IgE receptors on mast cells and mediate the release
      of various mast cell-derived mediators and proinflammatory cytokines on exposure
      to allergen. Clinically significant allergic responses are followed by a late
      phase response dominated by eosinophils and T lymphocytes. The majority of T
      cells in allergic responses are memory T cells secreting helper type 2 (TH2)-like
      cytokines, i.e., interleukin (IL)-4, IL-5, IL-13, but not interferon-gamma. These
      cytokines regulate IgE synthesis and promote eosinophil development, thus
      contributing to allergic inflammatory responses. Failure to control immune
      activation early in the course of allergic disease blunts responses to
      glucocorticoid therapy and contributes to disease progression. The identification
      of key cells and molecules involved in the initiation and maintenance of allergic
      inflammation is likely to become an important target in the treatment of this
      common group of illnesses.

PMID- 9608538
TI  - Cloning and characterization of the mouse and rat type II arginase genes.
AB  - Two forms of arginase, both catalyzing the hydrolysis of arginine to ornithine
      and urea, are found in animals ranging from amphibians to mammals. In humans,
      inherited deficiency of hepatic or type I arginase results in hyperargininemia, a
      syndrome characterized by periodic episodes of hyperammonemia, spasticity, and
      neurological deterioration. In these patients, a second extrahepatic or type II
      arginase activity is significantly increased, an induction that may partially
      compensate for the lack of AI activity and apparently mitigates some of the
      clinical effects of the condition. Cloning and characterization of the human AII
      cDNA was recently accomplished. The cloning, sequencing, and partial
      characterization of the mouse and rat AII cDNAs are reported herein. The DNA
      sequences predicted polypeptides of 354 amino acids, including a N-terminal
      mitochondrial import signal. Sequence homology to the human type II arginase,
      arginase activity data, and immunoprecipitation with an anti-AII antibody confirm
      the identity of these cloned genes as rodent extrahepatic type II arginases.

PMID- 9608539
TI  - Energy-dependent intracellular translocation of glucokinase in rat pancreatic
      islets.
AB  - It was recently reported that hyperglycemia provokes a rapid and sustained
      translocation of glucokinase in rat pancreatic B-cells, and it was speculated
      that this may be associated with enhancement of its catalytic activity, as
      possibly attributable to the mitochondrial binding of the enzyme. In the present
      work, the activities of both hexokinase and glucokinase were measured in
      particulated and cytosolic subcellular fractions prepared from islets first
      incubated for 60 min either in the absence of exogenous nutrient or in the
      presence of D-glucose, tested at both low (2.8 mmol/L) and high (16.7 mmol/L)
      concentrations. The relative contribution of the cytosolic domain to the total
      activity of glucokinase recovered in the two subcellular fractions was higher in
      islets deprived of exogenous nutrient than in islets first exposed to 2.8 or 16.7
      mmol/L D-glucose, the results obtained at each of the latter two hexose
      concentrations being comparable to one another. The subcellular distribution of
      hexokinase, however, was not significantly different in islets deprived of D
      glucose or exposed to the hexose. These findings are interpreted as indicative of
      an energy-dependent translocation of glucokinase in the B-cell, distinct from the
      redistribution of the enzyme occurring in response to a rise in D-glucose
      concentration above its physiological value.

PMID- 9608540
TI  - Regulation of agonist-receptor binding by G proteins and divalent cations in
      spermatozoa solubilized A1 adenosine receptors.
AB  - Solubilized A1 adenosine receptor (A1AR) was used to investigate the effect of
      several cations on agonist-binding characteristics and GTP hydrolysis. It was
      shown by Western blot with G beta-M14 that this preparation contains both G
      proteins and receptor. The role of the receptor molecule is to facilitate the
      activation of G proteins as alpha-GTP complex, and GTP hydrolysis has important
      consequences for the basic deactivation mechanism. Divalent cations, such as
      Mn2+, Ca2+, and Mg2+, potentiated the agonist-specific binding: Mn2+ had the
      highest apparent affinity with half-maximal effect at 50 microM. Binding assays,
      performed in the presence of 100 microM Mn2+, showed an increase in the apparent
      affinity of the binding sites, whereas, in the presence of 1 mM Mg2+, significant
      alteration of the apparent affinity, but not of the number of sites, was
      detected. Concentrations of 1 mM Mg2+ and 100 microM Mn2+ enhanced GTPase
      activity, whereas 5 mM Ca2+ resulted in the increase of Vmax values without
      significant alterations of K(m). In the presence of A1-specific agonists, Mn2+
      and Mg2+ caused a decrease of Vmax values and an increase of GTP affinity. Other
      cations, such as Co2+, Cd2+, Cu2+, and Zn2+, inhibited the binding capacity but
      caused almost no changes in GTP hydrolysis kinetics.

PMID- 9608541
TI  - Free radical generators cause changes in endothelial and inducible nitric oxide
      synthases and endothelin-1 immunoreactivity in endothelial cells from
      hyperlipidemic rabbits.
AB  - Reactive oxygen species (ROS) play an important role in the damage of vascular
      endothelium during atherogenesis and impaired endothelium-dependent
      vasorelaxation. We have studied the effect of two ROS generators (H2O2 and
      menadione) and one of the most potent antioxidants (morin) on the double
      immunofluorescent staining of endothelial cells (EC) from both Watanabe Heritable
      Hyperlipidemic (WHHL) and New Zealand White (NZW) rabbits in primary cultures
      using antibodies against endothelin-1 (ET-1), endothelial (eNOS), and inducible
      nitric oxide synthase (iNOS). In aortic EC from normal rabbits, ROS decreased the
      immunoreactivity of eNOS and ET-1 and this effect was significantly reversed by
      morin. In atherosclerotic rabbits, ROS had the same effect on the
      immunoreactivity of eNOS and ET-1 but also induced the expression of iNOS
      immunoreactivity. In general, the cells from WHHL rabbits were less sensitive to
      the protective effects of morin and more sensitive to the effects of ROS. It thus
      appears that the protective effect of morin may be due to neutralization of ROS
      and may be considered for the treatment of early stages of atherosclerosis,
      before macroscopic lesions have occurred.

PMID- 9608542
TI  - Expression of human alpha 1 antitrypsin in murine hematopoietic cells in vivo
      after retrovirus-mediated gene transfer.
AB  - For patients with alpha1 antitrypsin (alpha 1AT) deficiency, the expression of
      alpha 1AT in hematopoietic cells may results in a number of benefits not provided
      by gene transfer strategies involving local modification of the respiratory
      epithelium or liver-directed gene transfer. We investigated the expression of
      alpha 1AT in murine hematopoietic cells after retrovirus-mediated gene transfer.
      For this purpose we constructed an LNL-6-derived recombinant retrovirus vector (L
      alpha 1ED) that expresses the alpha 1AT cDNA from the Moloney murine leukemia
      virus (MoMuLV) U3 promoter/enhancer and coexpresses the cDNA for a mutant form of
      the murine dihydrofolate reductase molecule (*DHFR) from the encephalomyocarditis
      virus (emc) internal ribosome entry site (IRES). All of the mice transplanted
      with bone marrow transduced with the L alpha 1ED vector expressed the alpha 1AT
      protein at the 3-week time point after transplantation. By the 6-week time point
      the alpha 1AT levels declined to a lower level, where they generally remained for
      the duration of the experiment. This study demonstrates the potential utility of
      hematopoietic cell gene transfer for gene therapy of alpha 1AT deficiency.

PMID- 9608543
TI  - The role of dietary zinc in modifying the onset and severity of spontaneous
      diabetes in the BB Wistar rat.
AB  - The goal of this study was to determine whether zinc supplementation in the diet
      of diabetes-prone BB Wistar rats will delay or prevent the onset of overt
      diabetes. Male Wistar BB rats were fed diets containing either 1000 ppm (HZ), 50
      ppm (NZ), or 1 ppm zinc (LZ) starting at 30 days of age. Non-diabetes-prone rats
      were fed NZ and designated as controls (NORM). Beginning at 60 days, the rats
      were checked for glycosuria and, if positive, were given an i.p. glucose
      tolerance test (IPGTT). All remaining animals underwent an IPGTT at 100 days and
      were sacrificed. At 90 days of age HZ rats had a lower incidence of diabetes
      (19%) than NZ (53%) or LZ (44%) animals (P < 0.015). By age 100 days, for the HZ
      group, there was a 60% reduction in the number of expected overt diabetic rats.
      HZ animals also had higher concentrations of both pancreatic and serum insulin
      and exhibited lower serum glucose and triglycerides. Immunohistochemistry of HZ
      rats was clearly different from NZ rats and showed evidence of nearly normal
      pancreatic endocrine activity. Data indicate that dietary treatment of diabetes
      prone BB Wistar rats with zinc appears to be an effective approach for delaying
      or preventing the onset of diabetes in genetically predisposed rodents. This
      finding may suggest further experimental studies regarding dietary means for
      preservation of pancreatic function.

PMID- 9608544
TI  - Response of insulin, glucagon, lactate, and nonesterified fatty acids to glucose
      in visceral obesity with and without NIDDM: relationship to hypertension.
AB  - Insulin, glucagon, glucose, nonesterified fatty acids (NEFA), and lactate
      response to oral glucose tolerance test (OGTT, 75 g glucose) and their
      correlation with mean blood pressure (BP), were studied in 10 normal subjects
      (N), 25 subjects with abdominal obesity (O), and 9 subjects with abdominal
      obesity and IGT or non-insulin-dependent diabetes (OD). O and OD patients, as
      compared to N subjects, showed increased fasting NEFA, lactate, insulin, and
      glucagon. NEFA area and insulin total and incremental areas were increased in O
      and OD (P < 0.001 in all instances). Glucagon total areas were increased only in
      OD (P < 0.01). Lactate total areas were increased in O (P < 0.001) and in OD (P <
      0.01), while lactate incremental area was diminished in O and, even more, in OD
      subjects (P < 0.001 in both instances) and was inversely correlated with the
      basal level (P < 0.001). In all subjects as a whole, increase in NEFA area was
      weakly correlated with total and incremental insulinemic areas (P < 0.05) and
      more strongly correlated with glucagon and lactate areas (P < 0.01). Conversely,
      the incremental areas of lactate were negatively correlated with total insulin (P
      < 0.05), NEFA (P < 0.05), and glucagon (P < 0.001) areas. BP was increased in O
      (103.62 +/- 2.37) and, even more, in OD (109.41 +/- 5.22) compared to that seen
      in N (92.55 +/- 0.94 mm Hg), with P < 0.01, and was correlated with fasting
      insulin (P < 0.01) and glucose (P < 0.05) and, even more, with total (P < 0.001)
      and incremental (P < 0.01) insulin areas and NEFA areas (P < 0.001). Conversely,
      BP also was negatively correlated with incremental lactate area (P < 0.01)
      (similarly to insulin and NEFA area). Our data would suggest that in O and OD
      patients, insulin resistance is associated with elevated NEFA, insulin and
      glucagon as well as with high BP. since NEFA are inhibitors of Na,K-ATPase, they
      could contribute to elevate BP through the repression of this enzyme (which we
      have shown previously to be reduced in adipose tissue of obese subjects and
      correlated negatively with BP.

PMID- 9608545
TI  - alpha-Tocopherol reduces proteinuria, oxidative stress, and expression of
      transforming growth factor beta 1 in IgA nephropathy in the rat.
AB  - Oxidative stress and the fibrogenic cytokine transforming growth factor beta 1
      (TGF beta 1) have been implicated in the pathogenesis and progression of IgA
      nephropathy. In the present study, we used alpha-tocopherol as a dietary
      supplement to test the hypothesis that the proteinuria, oxidative stress, and TGF
      beta mRNA can be more effectively lowered with higher doses of alpha-tocopherol.
      Hematuria, proteinuria, and mesangial IgA deposition are parameters which
      characterize IgA nephropathy. IgA nephropathy was induced by bovine gamma
      globulin oral immunization in rats during an 8-week course, and all hallmarks of
      IgA nephropathy were produced in this 8-week animal model. The elevation in renal
      malondialdehyde content and TGF beta 1 mRNA, as well as the severity of
      proteinuria, was blunted by alpha-tocopherol. Our data suggested that
      conventional dosage of alpha-tocopherol at 100 IU/kg chow lowered kidney TGF beta
      1 to control values and increasing the dose by 2 1/2-fold or even 5-fold resulted
      in no further reduction in TGF beta 1 mRNA. Significant reduction of proteinuria
      was achieved better with a dose of 250 IU/kg chow of alpha-tocopherol
      supplementation than with the 100 IU/kg chow. We conclude that alpha-tocopherol
      at this dose is efficacious in controlling proteinuria, downregulating TGF beta
      1, and reducing oxidative stress in experimental IgA nephropathy. Doubling this
      dose achieved no further benefits.

PMID- 9608546
TI  - The Fanconi anemia complementation group A protein contains a peroxidase domain.
AB  - Computational analysis of the Fanconi anemia (FA) complementation group A protein
      suggests that it contains a peroxidase domain. FA proteins may be part of a
      general mechanism that protects cells from oxidative damage.

PMID- 9608547
TI  - Activation of membrane skeleton-bound phosphofructokinase in erythrocytes induced
      by serotonin.
AB  - We show here that serotonin, both in vivo and in vitro, induced a marked
      activation of phosphofructokinase, the rate-limiting enzyme in glycolysis, in the
      membrane-skeleton fraction from erythrocytes. Concomitantly, the hormone induced
      a striking increase in lactate content, reflecting stimulation of glycolysis. The
      enzyme's activity in the cytosolic (soluble) fraction remained unchanged. These
      results suggest a defense mechanism in the erythrocytes against the damaging
      effects of serotonin, whose concentration in plasma increases in many diseases
      and is implicated as playing an important role in circulation disturbances.

PMID- 9608548
TI  - Studies on human porin. XVI: Polyamines reduce the voltage dependence of human
      VDAC in planar lipid bilayers--spermine and spermidine inducing asymmetric
      voltage gating on the channel.
AB  - We present the first data on the effects of polyamines on human VDAC. Purified
      VDAC in lipid bilayers shows lowered voltage dependence whenever putrescine,
      cadaverine, spermine, spermidine, or the histamine releaser Compound 48/80,
      respectively, are applied. Only spermine and spermidine induce an asymmetric
      reaction on the channel. However, we state a groupwise different reaction of
      polyamines, which are organic polycations, on human porin.

PMID- 9608549
TI  - [Disorders of neuromuscular transmission].
AB  - Disorders of neuromuscular transmission include a heterogenous group of diseases
      affecting the neuromuscular junction. The most important clinical syndrome is
      idiopathic myasthenia gravis. As a group, these disorders exhibit several common
      features, the essential one being a fluctuating fatigability and weakness of
      muscles. In this short review the molecular pathogenesis of different myasthenic
      syndromes is discussed.

PMID- 9608550
TI  - [Botulinum toxin: mechanism of action].
AB  - Inhibitory effect of botulinum toxin on acetylcholine release from the neurons of
      peripheral nervous system and morphological changes produced in neuro-muscular
      junction by administration of the toxin are discussed. Other possible mechanisms
      of action, which can be responsible for the therapeutic effect are presented. Two
      clinically important problems are discussed: spreading of the toxin from the site
      of injection, and immunization which is responsible for non-responsiveness in
      some cases.

PMID- 9608551
TI  - [Botulinum A toxin in the treatment of focal dystonias].
AB  - There are 3 clinical groups of dystonia: generalized, segmental and focal.
      Spasmodic torticollis, blepharospasmus, laryngeal dystonia and graphospasmus
      belong to the focal dystonia. The aetiology of dystonias is not clear but genetic
      factors are commonly accepted. Treatment with pharmacological and surgical
      methods is not satisfactory. Botulinum toxin A(BTX) has brought a new approach to
      the effective treatment of dystonias. Effectiveness of this method is estimated
      as 60 to 100%, depending on clinical factors, department and author. BTX acts on
      neuro-muscular junction and produces chemical denervation but the effect is not
      persistent and after 3 or more months the treatment should be repeated. The
      method is harmless and can be administered in out-patients practice. Adverse
      events are observed in 10% patients but they are not serious and transient.
      Details are described the methods of BTX injections in spasmodic torticollis,
      blepharospasmus and laryngeal dystonia.

PMID- 9608552
TI  - [Treatment of writer's cramp and other forms of limb dystonias with botulinum
      toxin].
AB  - All forms of limb dystonia can be treated with botulin toxin injection. The
      selection of dystonic muscles and performing the injections in writer's cramp are
      discussed in detail. Treatment strategy and outcome in other forms of limb
      dystonia are presented.

PMID- 9608553
TI  - [Botulinum toxin in the treatment of tremor].
AB  - Pharmacological treatment of essential and symptomatic tremor is not
      satisfactory. Introduction of botulinum toxin (BTX) has brought a new approach to
      tremor treatment. BTX is injected into carpal flexors and extensors about 100
      i.u. into each muscle, higher doses are injected into flexors and lower into
      extensors. Beneficial results are observed in 50 to 67% of the patients. The
      author treated 5 patients with tremor of various origin with good result in 3
      cases (60%), but in all cases weakness of hand muscles and middle finger dropping
      were observed. BTX treatment is indicated in certain cases of hand disabled by
      tremor.

PMID- 9608554
TI  - [Botulinum toxin in the treatment of pain].
AB  - Botulinum toxin (BTx) has been administered for many years in the treatment of
      dystonias with great success. Its effectiveness is comparable with the best
      drugs. It was observed during spasmodic torticollis treatment that pain
      disappears as first before clinical improvement of dystonia. Different mechanisms
      of influence of BTx on pain are discussed. BTx was tried in tension headache,
      cluster headache, migraine, fibromyositis, painful cramps with varying results.
      It is possible that BTx will be useful in many other types of pain.

PMID- 9608555
TI  - [Treatment of hemifacial spasm with botulinum A toxin].
AB  - The authors present the method of hemifacial spasm treatment with botulinum toxin
      discussing the results of the treatment, injection method, side effects and
      complications of this treatment on the basis of literature review and their own
      experience. Clinical features, aetiology and pathophysiology of this condition
      are described. Other treatment methods are briefly mentioned.

PMID- 9608556
TI  - [Botulinum toxin in spasticity treatment].
AB  - The author reviews the current opinions on the treatment of spasticity with
      special consideration given to the new method of treatment with local injections
      of botulinum toxin A into the spastic muscles. Botulinum toxin is the treatment
      of choice in focal dystonias and hemifacial spasm. The mechanism of action of the
      toxin is unique and is a result of dose-dependent and partial chemical
      denervation of the muscles, with preservation of tonus and thus its function.
      Recent reports have confirmed the safety and effectiveness of the method in
      spasticity, especially when it is focal, not diffuse or severe and without
      concomitant severe paresis. The author describes also the basic data of the
      pathophysiology of spasticity and reviews other therapeutic options and practical
      problems concerning the injections of botulinum toxin.

PMID- 9608557
TI  - [Botulinum toxin injections under electromyographic guidance].
AB  - EMG can be used for both dystonic muscles selection and performing injections of
      botulinum toxin. The indications for performing injections under EMG guidance in
      different forms of movement disorders are discussed. There is no need of EMG
      control in the treatment of blepharospasm and hemifacial spasm. In cervical
      dystonia the use of EMG guidance can improve the results of treatment in cases of
      head tilt, retrocollis, shoulder elevation and in more complex forms of dystonia.
      The injections should be performed under EMG control in patients with limb, oro
      mandibular and laryngeal dystonia and with palatal myoclonus.

PMID- 9608558
TI  - Oral exfoliative cytology for the non-invasive diagnosis in X-linked Emery
      Dreifuss muscular dystrophy patients and carriers.
AB  - Emery-Dreifuss muscular dystrophy (EMD) is an inherited myopathy characterised by
      muscle contractures, progressive muscle wasting and weakness, with humeroperoneal
      distribution. Cardiac arrhythmia and heart conduction block are also important
      characteristics of this disease. The X-linked form of EMD is caused by the
      absence of emerin, encoded by the STA gene (Xq28). Emerin is normally localized
      in muscle and other tissues at the nuclear rim. Currently, muscle and skin
      biopsies are used for the immunohistochemical diagnosis. We demonstrate that
      emerin is present in the cheek oral mucosa, in the exfoliating epithelial cells,
      and we propose the collection of these cells as a new method for the diagnosis of
      X-linked EMD patients and the detection of carriers by immunofluorescence
      techniques: smears from healthy subjects contained about 98% emerin-positive
      cells, those from X-linked EMD patients contained none and those from carriers
      contained about 45%. The technique is completely non-invasive, simple, repeatable
      and inexpensive.

PMID- 9608559
TI  - Early presentation of X-linked Emery-Dreifuss muscular dystrophy resembling limb
      girdle muscular dystrophy.
AB  - Emery-Dreifuss muscular dystrophy is an X-linked neuromuscular disorder caused by
      defects in the STA gene on Xq28, which codes for a nuclear protein named emerin.
      Affected patients usually present in early adolescence with scapulo-peroneal
      muscle weakness and wasting, and contractures of the tendo Achilles, elbows and
      paraspinal muscles, resulting in spine rigidity. We present here a case of Emery
      Dreifuss muscular dystrophy with an unusually severe, early presentation. He
      presented at 2.5 years with predominantly proximal weakness and mild equinovarus
      deformity of the right foot. Serum creatine kinase activity was elevated (1994
      IU/I) and a muscle biopsy at the age of 4 years showed marked dystrophic
      abnormalities. Normal expression of dystrophin, and no detectable deletion in the
      corresponding gene, excluded a diagnosis of Duchenne muscular dystrophy.
      Similarly, normal expression of alpha-sarcoglycan made a limb-girdle muscular
      dystrophy caused by a defect in a sarcoglycan unlikely. Several years later,
      examination of the proband's maternal cousin, aged 14 years, suggested Emery
      Dreifuss muscular dystrophy. This was confirmed in both affected boys by the
      absence of emerin in muscle and leucocytes, and identification of a mutation in
      exon 4 of the STA gene. Carrier status in both mothers was also confirmed by
      mutational and protein analysis. Emery-Dreifuss muscular dystrophy should
      therefore be considered in the differential diagnosis of cases of early onset
      muscular dystrophy, even in the absence of the typical clinical features.

PMID- 9608560
TI  - Familial cardiomyopathy and distal myopathy with abnormal desmin accumulation and
      migration.
AB  - Desminopathies form a heterogeneous group of myopathies characterised by
      pathological aggregations of desmin. We report a family, where mother and
      daughter presented with an atrioventricular block and a slowly progressive distal
      muscular weakness, with non-homogeneous focal atrophy on computed tomography
      scans. The mother developed a severe global heart insufficiency necessitating a
      heart transplantation at 56 years of age. Skeletal muscle biopsies were
      characterised by inclusion bodies strongly expressing desmin and alpha B
      crystallin, with a predominantly subsarcolemmal localisation. Ultrastructurally
      most inclusions corresponded to non-membrane bound granulo-filamentous material
      with disruption of myofibrils. An immunoblot showed a hyperintense desmin band at
      53 kDa and a second band at 49 kDa, the latter being absent in controls. The
      cardiac muscle of the explanted heart showed very similar inclusions. These cases
      illustrate that in this distinct subtype of desminopathies the cardiac muscle
      alterations are comparable with those observed in skeletal muscle, and suggest
      the possibility of a primary desmin pathology.

PMID- 9608561
TI  - Demyelinating neuropathy in a patient with multiple sclerosis and genotypical
      HMSN-1.
AB  - Patients with multiple sclerosis (MS) may develop a peripheral neuropathy,
      sometimes attributed to nutritional deficiency. Other patients present with a
      demyelinating neuropathy which is presumed to be the result of an autoimmune
      process that affects both the central and peripheral nervous systems. We report a
      case of concurring MS and demyelinating neuropathy, without a positive family
      history, in whom genetic testing proved the neuropathy to be hereditary and not
      autoimmune. Hereditary neuropathy should be a consideration in sporadic cases of
      peripheral neuropathy and MS.

PMID- 9608562
TI  - HMSNL in a 13-year-old Bulgarian girl.
AB  - We present a 13-year-old Bulgarian girl with a new form of demyelinating
      neuropathy with hearing loss. The clinical and neuropathological features of the
      patient were similar to those of the recently described hereditary motor and
      sensory neuropathy type Lom (HMSNL), first identified in a large Bulgarian Gypsy
      population. Neuropathological examination of a peripheral nerve biopsy revealed
      an excess of nerve fibres with inappropriately thin myelin sheaths compared with
      the axon diameter, surrounded by concentric Schwann cells without typical onion
      bulb formation. The parents of our patient are unaware of Gypsy ancestry and are
      not in a consanguineous marriage. Genetic analyses showed that the patient was
      homozygous for the predominant HMSNL haplotype on 8q24. Our findings indicate
      that HMSNL should be considered in the differential diagnosis of any patient
      presenting with the symptoms of demyelinating neuropathy with hearing loss, even
      if no Gypsy ethnic background is reported.

PMID- 9608563
TI  - Myoblast transplantation in non-dystrophic dog.
AB  - Dog myoblasts obtained from muscle biopsies were infected in vitro with a
      defective retroviral vector containing a cytoplasmic beta-galactosidase (beta
      Gal) gene. These myoblasts were initially transplanted in the irradiated muscles
      of SCID mice and beta-Gal positive muscle fibers were observed. beta-Gal
      myoblasts were also transplanted back either in the donor dogs
      (autotransplantation model) or in unrelated recipient dogs (allotransplantation
      model). Following these myoblast injections, a rapid inflammatory reaction
      developed within the muscle as indicated by an expression of P-selectin and of
      pro-inflammatory cytokine mRNAs (interleukin 6 (IL-6) and transforming growth
      factor beta (TGF-beta), and by a neutrophil infiltration. Following either auto-
      or allotransplantation in inadequately or non-immunosuppressed dogs, a specific
      immune reaction also developed within 2 weeks as indicated by the infiltration of
      CD4+ and of CD8+ lymphocytes, the increased expression of IL-10 and granzyme B
      mRNAs and the presence of antibodies reacting with the injected cells. Some dogs
      were immunosuppressed with several combinations of FK506, cyclosporine (CsA) and
      RS-61443. In dogs immunosuppressed with CsA combined with RS-61443, only a few
      myoblasts and myotubes expressing beta-Gal were observed 1-2 weeks after the
      transplantation, but no muscle fibers expressing beta-Gal were observed after 4
      weeks, and antibodies against the injected cells were formed. In dogs
      immunosuppressed with FK506 alone, although no antibodies against the injected
      cells were produced, there were no small cells and no muscle fibers expressing
      beta-Gal 1 month after the transplantation. However, FK506 triggered diarrhea and
      vomiting in dogs. When the dogs were immunosuppressed with FK506 combined with
      CsA and RS-61443, muscle fibers expressing beta-Gal were present 4 weeks after
      the transplantation and no antibodies reacting with donor myoblasts were
      detected. These results indicate that the combination of three immunosuppressive
      agents (i.e., FK506, CsA and RS-61443) is effective in controlling the specific
      immune reactions following myoblast transplantation in dogs and they underline
      that the outcome of myoblast transplantation is dependent in part on an adequate
      immunosuppression. These results obtained here in normal dogs may justify
      myoblast transplantation in dystrophic dogs despite the side effects of FK506.

PMID- 9608564
TI  - Welander hereditary distal myopathy, a molecular genetic comparison to hereditary
      myopathies with inclusion bodies.
AB  - Welander distal myopathy (WDM) is an autosomal dominant disorder with late onset
      predominantly affecting distal extensor muscles of the hands and the feet. The
      disorder is considered as the most common of the distal myopathies but is almost
      only seen in Sweden and some parts of Finland. The finding of rimmed vacuoles in
      muscle biopsies from patients with moderate and severe symptoms constitutes one
      similarity with hereditary inclusion body myopathy (HIBM) sparing the quadriceps
      as described by Argov and Yarom [Argov Z, Yarom R. J Neurol Sci 1984;64:33-43].
      The question has been raised whether some of the different forms of distal
      myopathy might be allelic. In previous reports the gene defects for HIBM and
      autosomal recessive hereditary distal myopathy with rimmed vacuoles (DMRV) have
      been mapped to chromosome 9pl-q1. The Finnish tibial muscular dystrophy (TMD)
      that displays similar histopathological findings has recently been linked to
      chromosome 2q. We have investigated the regions of interest with dispersed
      microsatellite markers in four well-described pedigrees, and this study now
      excludes the regions on chromosome 9pl-q1 and 2q from linkage to WDM both by
      haplotype analysis and linkage analysis with the MLINK program. WDM, showing
      morphological similarities with HIBM, is clearly separated from the disorders
      mapped to chromosomes 9 and 2 on clinical and genetical grounds.

PMID- 9608565
TI  - Welander distal myopathy--an overview.
AB  - Welander distal myopathy has an autosomal dominant inheritance and a late onset.
      The onset of symptoms is in the hands and gradually distal muscles of the lower
      extremities are involved. The most-affected muscles are the long extensors of the
      hands and feet. CK-values are normal or slightly elevated. There is never any
      cardiac involvement in Welander distal myopathy. Neurophysiological findings are
      of both myopathic and neuropathic character. Histopathological findings in muscle
      biopsies are mainly of myopathic type and include rimmed vacuoles which
      correspond to autophagic vacuoles on the ultrastructural level. Tubulo
      filamentous inclusions with a diameter of 16-21 nm, i.e. of the same type as
      found in patients with Inclusion Body Myositis, are found in the sarcoplasm and
      in myofibre nuclei. A neurogenic component in Welander distal myopathy has been
      suggested, on the grounds of a sensory dysfunction, neuropathic findings on
      neurophysiology and muscle biopsy and a decrease of A-delta nerve fibres on sural
      nerve biopsy. Genetic analysis has excluded linkage to other defined distal
      myopathies and hereditary Inclusion Body Myopathy loci.

PMID- 9608566
TI  - Autosomal recessive oculopharyngodistal myopathy in light of distal myopathy with
      rimmed vacuoles and oculopharyngeal muscular dystrophy.
AB  - We investigated two Japanese siblings presenting with oculopharyngodistal
      myopathy, whose healthy parents were consanguineous. To clarify their disease
      characteristics, we compared them with four patients with distal myopathy with
      rimmed vacuoles linked to chromosome 9p1-q1, and 36 patients with oculopharyngeal
      muscular dystrophy linked to 14q11.2-q13. The first symptom in the patients with
      autosomal recessive oculopharyngodistal myopathy was weakness of the tibialis
      anterior muscle. Their biceps muscles showed initial and advanced myogenic
      changes, with rimmed vacuoles in 3% and 6% of the muscle fibers, respectively. In
      contrast, patients with distal myopathy with rimmed vacuoles revealed many rimmed
      vacuoles, on average in 20% of the fibers, and their oculopharyngeal muscles were
      spared. None of the patients with oculopharyngeal muscular dystrophy showed
      distal dominant weakness and the occurrence of rimmed vacuoles was rare.
      Ultrastructural studies in groups of autosomal recessive oculopharyngodistal
      myopathy and distal myopathy with rimmed vacuoles disclosed a collection of
      cytoplasmic filaments of 16-18 nm, but oculopharyngeal muscular dystrophy
      specific intranuclear inclusions of 8.5 nm were not found. Thus, the phenotype of
      autosomal recessive oculopharyngodistal myopathy is distinct from distal myopathy
      with rimmed vacuoles and oculopharyngeal muscular dystrophy, but shares some
      ultrastructural characteristics with distal myopathy with rimmed vacuoles and
      hereditary inclusion body myopathy.

PMID- 9608568
TI  - Neuromuscular disorders: gene location.

PMID- 9608567
TI  - 44th ENMC International Workshop: Facioscapulohumeral Muscular Dystrophy:
      Molecular Studies 19-21 July 1996, Naarden, The Netherlands.

PMID- 9608569
TI  - Mitochondrial encephalomyopathies: gene mutation.

PMID- 9608570
TI  - Congenital myasthenic syndromes: gene mutation.

PMID- 9608571
TI  - Persistent QEEG abnormality in crack cocaine users at 6 months of drug
      abstinence.
AB  - The major objective of this study was to examine the persistence of abnormal
      quantitative EEG (qEEG) measures over a six month time interval in subjects in
      strictly supervised drug free residential treatment for crack cocaine dependence.
      Seventeen subjects were assessed with qEEG at five to 10 days, one month and six
      months following their last use of cocaine. No significant changes were noted
      over time in abnormal qEEG measures, which included deficits of absolute and
      relative power in the delta band and increased relative alpha power. The
      persistence of qEEG abnormality in crack cocaine withdrawal suggests a persistent
      neurobiologic alteration resulting from chronic cocaine exposure. The specificity
      of the qEEG findings is discussed, and an interpretation is suggested with
      reference to the hypothesis of neural sensitization in cocaine dependence.

PMID- 9608572
TI  - Effect of cocaine-related environmental stimuli on the spontaneous
      electroencephalogram in polydrug abusers.
AB  - Relationships between the spontaneous electroencephalogram (EEG), self-reports of
      cocaine craving, and cerebral glucose metabolism, determined using 2-[18F]fluoro
      2-deoxy-D-glucose and positron emission tomography, were assessed during the
      presentation of either neutral or cocaine-related environmental stimuli. In
      cocaine users but not non-drug-abusing controls, EEG power in the alpha1 and
      alpha2 frequency bands was significantly lowered during presentation of the drug
      related stimuli when compared with the neutral test session. Decreases in alpha1
      power were negatively correlated with increases in global glucose metabolism but
      were not correlated with either the time course or the magnitude of craving
      throughout the 30-min test session. Although EEG desynchronization is related to
      global brain metabolism, the difference in the time courses between EEG power and
      craving suggests that self-reports of cue-elicited cocaine craving do not simply
      reflect increases in the state of cortical arousal.

PMID- 9608573
TI  - Effects of continuous D-amphetamine and phencyclidine administration on social
      behaviour, stereotyped behaviour, and locomotor activity in rats.
AB  - D-amphetamine (AMPH) and phencyclidine (PCP) can induce a model psychosis that
      mimic the positive symptoms of schizophrenia, but only PCP also mimics the
      negative symptoms. Recent studies in the rat social interaction test have shown
      that PCP, and not AMPH, induce social withdrawal following single and repeated
      injections, and this effect may, therefore, be used to model negative symptoms.
      However, an AMPH psychosis is usually only seen after a prolonged period of
      repeated injections or continuous administration for 3-5 days of high doses of
      AMPH. It is, therefore, possible that in these studies, AMPH was administered at
      insufficient levels in rats, and this may explain its lack of effect. The present
      study has determined the effects of continuous administration of AMPH (23 to 94
      mumol/kg/day; 4.2 to 17 mg/kg/day) and PCP (18 to 107 mumol/kg/day; 5.0 to 30
      mg/kg/day) in rats after five days of infusion in the social interaction test and
      after 6-7 days in standard activity cages. The study found that AMPH and PCP dose
      dependently induced stereotyped behaviour and locomotor hyperactivity, behaviours
      believed to be related to positive symptoms, and that only PCP induced social
      withdrawal. These findings confirm previous studies that only PCP and not AMPH
      induce deficits in the social behaviour of rats.

PMID- 9608574
TI  - Tryptophan depletion during continuous CSF sampling in healthy human subjects.
AB  - The tryptophan (TRP) depletion paradigm has been employed to investigate mood and
      behavioral effects of acutely lowering plasma TRP, and presumably brain serotonin
      (5-hydroxytryptamine [5-HT]) levels through administration of a special diet
      and/or amino acid drink. Our goal was to test the assumption that a corresponding
      fall in central levels of TRP and 5-HT (measured by its major metabolite, 5
      hydroxyindoleacetic acid [5-HIAA]) occurs during the standard execution of this
      method in healthy adult subjects. Three males and two females completed the
      protocol, which included a one-day low-TRP diet and a TRP-free amino acid drink.
      Lumbar puncture was performed, with placement of an indwelling catheter connected
      to a peristaltic pump and fraction collector. Cerebrospinal fluid (CSF) was
      sampled continuously for a 13.5-hour period (before, during, and after the
      drink), with fractions removed every 15 minutes. Plasma samples were
      simultaneously obtained. CSF TRP levels and plasma TRP levels were highly
      correlated, falling a mean of 92% and 85% from baseline, respectively. CSF nadirs
      were reached several hours after plasma nadirs. CSF 5-HIAA decreased modestly
      (24% to 40%, mean 31% change from baseline), with lowest concentrations observed
      8-12 hours after the amino acid drink. These data suggest that TRP depletion
      results in substantial declines in central 5-HT turnover.

PMID- 9608575
TI  - Abnormalities in the distributed network of sustained attention predict
      neuroleptic treatment response in schizophrenia.
AB  - The regional cerebral metabolic rates of 19 male medication-withdrawn
      schizophrenic patients were determined by positron emission tomography (PET)
      while performing an auditory discrimination task (CPT). Regardless of the
      accuracy of their CPT performance, the schizophrenic patients had lower metabolic
      rates in their prefrontal cortex and higher rates in their posterior putamen
      compared to 41 healthy males. Abnormally low right anterior midprefrontal cortex
      metabolic rates predicted better clinical response while high basal ganglia rates
      and low mid-cingulate rates predicted poor treatment response to neuroleptics.
      The findings imply that the sustained attention pathway and its distributed
      network of brain structures are likely to play an important role in the
      expression of psychotic symptoms and the mediation of their response to
      antipsychotics.

PMID- 9608576
TI  - Time-dependent changes in cocaine-seeking behavior and extracellular dopamine
      levels in the amygdala during cocaine withdrawal.
AB  - Cocaine and cocaine-associated cues elicit craving in addicts and reinstate
      cocaine-seeking behavior in rats. Craving and cocaine-seeking behavior may be
      mediated by withdrawal-induced changes in dopamine (DA) neurotransmission in the
      amygdala. To examine whether there are concomittant changes in cocaine-seeking
      behavior and extracellular DA levels during withdrawal, experimental rats were
      trained to self-administer cocaine (0.75 mg/kg i.v.). After 14 daily 3-hour
      training sessions, animals underwent either a 1-day, 1-week, or 1-month
      withdrawal period. Extracellular DA levels were assessed during baseline,
      extinction, cue reinstatement, and cocaine (15 mg/kg i.p.) reinstatement of
      cocaine-seeking behavior (i.e., defined as the difference in nonreinforced lever
      presses on an active minus inactive lever). Cocaine-seeking behavior became more
      intense during the course of cocaine withdrawal. Additionally, basal and cocaine
      induced extracellular DA levels were enhanced after the 1-month withdrawal
      period. We suggest that the former may reflect a persistent elevation in tonic
      extracellular DA levels in the amygdala, whereas the latter may reflect a
      persistent elevation in phasic extracellular DA levels.

PMID- 9608577
TI  - Combined nicotinic and muscarinic blockade in elderly normal volunteers:
      cognitive, behavioral, and physiologic responses.
AB  - Establishing a pharmacologic model of the memory deficits of Alzheimer's disease
      could be an important tool in understanding how memory fails. We examined the
      combined effects of the muscarinic antagonist scopolamine and the nicotinic
      antagonist mecamylamine in eight normal elderly volunteers (age 61.9 +/- 8.3 yrs,
      SD). Each received four separate drug challenges (scopolamine (0.4 mg i.v.),
      mecamylamine (0.2 mg/kg up to 15 mg PO), mecamylamine + scopolamine, and
      placebo). There was a trend toward increased impairment in explicit memory for
      the mecamylamine + scopolamine condition as compared to scopolamine alone.
      Increased impairment was also seen for the mecamylamine + scopolamine condition
      as compared to scopolamine alone in selected behavioral ratings. Pupil size
      increased when mecamylamine was added to scopolamine, while systolic blood
      pressure and pulse changed in concordance with ganglionic blockade. These data
      together with previous brain-imaging results suggest that this muscarinic
      nicotinic drug combination may better model Alzheimer's disease than either drug
      alone.

PMID- 9608578
TI  - Effect of mental stress on plasma homovanillic acid in healthy human subjects.
AB  - Plasma levels of homovanillic acid (pHVA) have been suggested to provide a
      measure of dopaminergic activity in the central nervous system. The present study
      investigated the effect of mental stress by the Kraepelin test, a test of
      continuous arithmetic addition of single-digit figures for 30 min, on pHVA levels
      in 13 male psychiatrically normal healthy volunteers. Following an overnight fast
      and restricted physical activity, plasma samples were collected immediately
      before and after the administration of the Kraepelin test. Plasma HVA levels
      following the administration of the Kraepelin test were significantly lower than
      the pretest pHVA levels. The percent change in pHVA levels by the Kraepelin test
      positively correlated with pretest pHVA levels. The observed reduction in pHVA
      levels by mental stress in normal subjects may reflect some aspects of a dopamine
      dependent restitutive system in the brain.

PMID- 9608579
TI  - M100907 and clozapine, but not haloperidol or raclopride, prevent phencyclidine
      induced blockade of NMDA responses in pyramidal neurons of the rat medial
      prefrontal cortical slice.
AB  - In the present study, we demonstrate that, in a concentration-dependent manner,
      M100907 (formerly MDL 100907, a highly selective 5-HT2A receptor antagonist and a
      purported atypical antipsychotic drug [APD]), but not its much less active
      stereoisomer M100009, completely prevents or markedly reverses the phencyclidine
      (PCP)-induced blockade of N-methyl-D-aspartate (NMDA) responses in pyramidal
      neurons of the medial prefrontal cortex (mPFC). Furthermore, the atypical APD
      clozapine, but not the typical APD haloperidol or raclopride (a selective
      dopamine D2,3 receptor antagonist), mimicked the action of M100907, preventing
      the PCP-induced effect. These results suggest that M100907 might be an antidote
      for treating the PCP-induced psychotomimetic state that closely resembles
      schizophrenia; they could also account for the antipsychotic potential of
      M100907. Furthermore, our results suggest that the prototype (clozapine) and a
      candidate (M100907) atypical APDs might be effective in ameliorating
      schizophrenic symptoms including cognitive and neuropsychological deficits, which
      are induced in humans who abuse PCP. We hypothesize that the ability of M100907
      and clozapine to prevent or reverse the PCP-induced blockade of the NMDA receptor
      channel is attributed to their 5-HT2A receptors antagonizing property. Therefore,
      with further systematic studies, the ability of compounds to prevent or reverse
      PCP's blockade of NMDA responses may prove to be an effective
      electrophysiological model for screening potential atypical APDs and predicting
      their therapeutic efficacy in cognitive deficits.

PMID- 9608580
TI  - Nitric oxide synthase inhibitors attenuate phencyclidine-induced disruption of
      prepulse inhibition.
AB  - Glutamate stimulation of N-methyl-D-aspartate (NMDA) receptors results in release
      of nitric oxide which may mediate the effects of NMDA receptor stimulation and/or
      may result in feedback inhibition of the presynaptic neuron. Results of a
      previous study showed that nitric oxide synthase (NOS) inhibitors blocked
      dizocilpine-induced behavior in mice. In the present study, NOS inhibitors were
      tested in combination with phencyclidine (PCP), a drug which typically dose
      dependently disrupts prepulse inhibition of the acoustic startle response in
      rats. Alone, NOS inhibitors and promoters do not affect prepulse inhibition;
      however, when tested in combination with PCP, the NOS inhibitors, L-NOARG, 7
      nitroindazole and arcaine--but not the NR2B-selective polyamine site NMDA
      antagonist, eliprodil--attenuated PCP-induced disruption of prepulse inhibition
      of the acoustic startle response. These effects are similar to those produced by
      many atypical antipsychotics and suggests that this class of drugs should be
      investigated further for their potential utility as antipsychotics and as
      treatments for PCP abuse.

PMID- 9608581
TI  - Plasma neuropeptide Y (NPY) increases in humans in response to the alpha 2
      antagonist yohimbine.
AB  - Previous studies have shown that the intravenous administration of yohimbine, an
      alpha 2 antagonist, increases norepinephrine turnover and has related anxiogenic
      effects in humans. We herein report that yohimbine also increases plasma
      neuropeptide Y (NPY) in healthy human subjects. This finding is consistent with
      previous reports in animals, but contrasts with a previously reported study in
      humans. NPY is a 36 amino acid peptide neurotransmitter located in sympathetic
      and nonsympathetic nerve fibers, as well as in brain structures such as the locus
      coeruleus, where it is colocalized with norepinephrine. NPY has been shown to
      inhibit locus coeruleus neuronal firing, decrease norepinephrine release, and
      increase postsynaptic noradrenergic signal transduction. When administered
      centrally, NPY also has anxiolytic properties. This study therefore suggests that
      yohimbine challenge may be useful in assessing NPY and noradrenergic system
      interactions in neuropsychiatric disorders such as panic disorder or post
      traumatic stress disorder in which noradrenergic system dysfunction has been
      observed.

PMID- 9608582
TI  - Effects of desmethylclozapine on Fos protein expression in the forebrain: in vivo
      biological activity of the clozapine metabolite.
AB  - Several products of the hepatic metabolism of clozapine are found in high
      concentrations in the plasma of schizophrenic patients treated with this atypical
      antipsychotic drug. One of these metabolites, N-desmethylclozapine, has
      substantially different affinities for dopamine and serotonin metabolites than
      does the parent compound. However, it is not known if this metabolite is active
      in vivo. We examined the effect of acute administration of desmethylclozapine to
      rats on forebrain Fos protein expression. Clozapine induces expression of this
      immediate-early gene in a distinct regional pattern in the brain.
      Desmethylclozapine significantly increased Fos protein expression in the medial
      prefrontal cortex and nucleus accumbens, but not in the dorsolateral striatum,
      thus mirroring the effects of the parent compound. These data indicate that the
      desmethyl metabolite of clozapine has in vivo biological activity.

PMID- 9608583
TI  - Nuclear magnetic resonance spectroscopy study of muscle growth, mdx dystrophy and
      glucocorticoid treatments: correlation with repair.
AB  - Proton nuclear magnetic resonance spectroscopy (1H NMR) can be used to study
      skeletal muscle metabolism. The mdx mouse is a unique animal for studies of
      muscle regeneration, and models the disease of Duchenne muscular dystrophy (DMD).
      The goals of this study were to determine the potential of 1H NMR spectroscopy as
      an alternative to conventional histology in monitoring: (1) normal growth in
      control muscle and the progression of dystrophy in mdx muscle, and (2) beneficial
      treatments (glucocorticoids) on mdx dystrophy. Ex vivo 1H NMR spectra of limb and
      diaphragm muscles were obtained from different ages of control and mdx mice, and
      from mice which were treated with prednisone or deflazacort. Peaks with
      contributions from creatine, taurine and lipids were examined. Lower levels of
      taurine and creatine characterized predystrophy and active dystrophy intervals in
      mdx muscle compared to control. Levels of taurine increased with stabilization of
      the disease by repair. A measure of accumulated muscle repair, fiber
      centronucleation and many spectral peaks were highly and significantly
      correlated. Greater amounts of lipids were found in the diaphragm compared to
      limb spectra. Treatment of dystrophy, which improved muscle phenotype, resulted
      in greater levels of taurine and creatine, especially in the limb muscle.
      Therefore, 1H NMR differentially discriminates: (1) control and mdx muscle; (2)
      the progression of mdx dystrophy and developmental stages in normal growth; (3)
      mild and severe dystrophic phenotypes (diaphragm vs limb); and (4) changes
      associated with improved muscle phenotype and regeneration (due to treatment or
      injury). The results focus on monitoring muscle repair, not degeneration. We
      conclude that 1H NMR is a reliable tool in the objective investigation of muscle
      repair status during muscular dystrophy.

PMID- 9608584
TI  - Monitoring of cell volume and water exchange time in perfused cells by diffusion
      weighted 1H NMR spectroscopy.
AB  - Diffusion of intracellular water was measured in perfused cells embedded in
      basement membrane gel threads. F98 glioma cells, primary astrocytes, and
      epithelial KB cells were used and were exposed to osmotic stress,
      immunosuppressiva, the water channel blocker p-chloromercuriobenzenesulfonate
      (pCMBS), and apoptotic conditions. With diffusion-weighted 1H NMR spectroscopy
      changes in the intracellular signal could be monitored and quantified with single
      signal (ss), constant diffusion time (ct), and constant gradient strength (cg)
      experiments. The temporal resolution of the ss monitoring was 3.5 s with a
      standard deviation of 0.5% of the signal intensity and 32 s (3%) with ct
      monitoring, respectively. A mean intracellular residence time of water was
      determined with the cg experiment to about 50 ms. Changes of this exchange time
      from (51.9 +/- 1.0) to (59.0 +/- 1.1) ms were observed during treatment with
      pCMBS. The changes in the diffusion attenuated signal could be simulated
      analytically varying the intracellular volume fraction and exchange time by
      combination of restricted diffusion (Tanner model) and water exchange (Karger
      model). This sensitive and noninvasive NMR method on perfused cells allows to
      determine changes in the intracellular volume and residence time in a simple and
      accurate manner. Many further applications as anoxia, volume regulation, ischemia
      and treatment with various pharmaceuticals are conceiveable to follow up their
      effect on the cell volume and the exchange time of intracellular water.

PMID- 9608585
TI  - Restricted diffusion and exchange of intracellular water: theoretical modelling
      and diffusion time dependence of 1H NMR measurements on perfused glial cells.
AB  - Intracellular diffusion properties of water in F98 glioma cells immobilized in
      basement membrane gel threads, are investigated with a pulsed-field-gradient spin
      echo NMR technique at diffusion times from 6 to 2000 ms and at different
      temperatures. In extended model calculations the concept of 'restricted
      intracellular diffusion at permeable boundaries' is described by a combined
      Tanner-Karger formula. Signal components in a series of ct experiments (constant
      diffusion time) are separated due to different diffusion properties (Gaussian and
      restricted diffusion), and physiological as well as morphological cell parameters
      are extracted from the experimental data. The intracellular apparent diffusion
      coefficients strongly depend on the diffusion time and are up to two orders of
      magnitude smaller than the self diffusion constant of water. Propagation lengths
      are found to be in the range of 4-7 microns. Hereby intracellular signals of
      compartments with a characteristic diameter could be selected by an appropriate
      gradient strength. With cg experiments (constant gradient) a mean intracellular
      residence time for water is determined to be about 50 ms, and the intrinsic
      intracellular diffusion constant is estimated to 1 x 10(-3)mm2/s. Studying the
      water diffusion in glial cells provides basic understanding of the intracellular
      situation in brain tissue and may elucidate possible influences on the changes in
      the diffusion contrast during ischemic conditions.

PMID- 9608586
TI  - New approach for quantitation of short echo time in vivo 1H MR spectra of brain
      using AMARES.
AB  - Short echo time in vivo STEAM 1H MR spectra (4.7 T, TE = 16 ms) of normal rat
      brain were fitted in the time domain using a VARPRO-like algorithm called AMARES
      which allows an inclusion of a large amount of prior knowledge. The prior
      knowledge was derived from phantom spectra of pure metabolite solutions measured
      under the same experimental conditions as the in vivo spectra. The prior
      knowledge for the in vivo spectra was constructed as follows: for each VARPRO
      fitted phantom spectrum one peak (the most prominent one in the in vivo spectrum)
      was chosen and left unconstrained in the AMARES fitting while all the other peaks
      in the metabolite spectrum (i.e. their corresponding parameters--amplitudes,
      damping factors, frequencies and phases) were fixed to the parameter values of
      the unconstrained peak via amplitude and damping ratios and frequency and phase
      shifts. Including N-acetyl-aspartate, glutamate, total creatine, cholines,
      glucose and myo-inositol into the fits provided results which were in agreement
      with published data. An inclusion of glutamine into the set of fitted metabolites
      was also investigated.

PMID- 9608587
TI  - Current awareness in NMR in biomedicine.

PMID- 9608588
TI  - A 1H/13C inverse 2D method for the analysis of the polyamines putrescine,
      spermidine and spermine in cell extracts and biofluids.
AB  - The polyamines putrescine, spermidine and spermine are involved in the regulation
      of various metabolic processes. It is therefore desirable to detect and quantify
      the polyamines with NMR. We present the proton and carbon assignments for all
      polyamine signals obtained from PCA extracts of F98 glioma cells with high
      resolution using a semi-selective HSQC 2D-experiment. The biosynthesis of the
      polyamines in cell culture was examined using the labeled substrates [U
      13C]glucose and [U-13C]glutamate. In such studies the high resolution of the semi
      selective HSQC experiment at very high magnetic fields (14-19 T) allows the
      analysis of carbon-carbon couplings, and isotopomer patterns. The different
      effects of osmotic stress on the concentrations of polyamines and amino acids are
      also reported.

PMID- 9608589
TI  - NMR spectroscopy and MRI investigation of a potential bioartificial liver.
AB  - NMR feasibility was established for a coaxial hydrophobic-membrane bioreactor
      containing isolated rat hepatocytes with features designed to mimic the human
      liver. A novel triple-tuned NMR probe and a perfusion system controlling
      temperature, gas concentrations, flow-rate, and pH were used. We determined the
      optimum coaxial interfiber distance (i.e. diffusion distance) for maintaining
      hepatocyte viability in two bioreactor prototypes. Prototype no. 1 and no. 2 had
      diffusion distances of 500 microns and 200 microns, respectively. Cell viability
      was established by 31P NMR and trypan blue exclusion. Only prototype no. 2
      maintained cell viability for more than 6 h, indicating the importance of
      diffusion distance. 31P spectra obtained over this 6 h time period were similar
      to in vivo spectra of rat liver. The 31P spectra were found to be more sensitive
      to subacute cell viability than trypan blue exclusion. In the 1H and 31P spectra,
      1H2O and inorganic phosphate signals were split in two at all flow-rates,
      probably due to bulk magnetic susceptibility effects originating from the three
      bioreactor compartments. MRI was useful for quality control and determining flow
      dynamics, fiber integrity, and cell inoculate distribution. MRI revealed that the
      inner fibers were not centered in either prototype. Although an increased flow
      rate did not influence spectral resolution or chemical shifts, significant
      degradation of MRI quality occurred above 50 mL/min. NMR spectroscopy and imaging
      provide valuable, real-time information on cell biochemistry and flow dynamics
      which can be used in development and monitoring of bioreactors designed as
      artificial livers.

PMID- 9608590
TI  - In vivo and in vitro bi-exponential diffusion of N-acetyl aspartate (NAA) in rat
      brain: a potential structural probe?
AB  - Diffusion measurements were performed on the N-acetyl aspartate (NAA) signal in
      in situ brains (in vivo and post-mortem) and on in vitro brain tissue at 37
      degrees C using wide ranges of b-values (from 0 up to 4.5 x 10(6) s/cm2 and 35.8
      x 10(6) s/cm2 for the in vivo and the in vitro cases, respectively). In vivo and
      in vitro NAA signals attenuation due to diffusion was measured at fixed diffusion
      times (tD). In the in vitro cases the effect of tD on the apparent diffusion
      coefficients (ADCs) of NAA was evaluated. From these experiments the following
      observations and conclusions were made: (1) NAA signal attenuation both in vivo
      and in vitro is not mono-exponential and could be fitted by bi-exponential
      fitting function; (2) analysis of the low b-value range only (up to 0.5 x 10(6)
      s/cm2) gives a mono-exponential decay (r = 0.999); (3) in both cases the obtained
      ADCs are sensitive to the diffusion time; (4) the ADCs of the pre- and post
      mortem cases are nearly similar; (5) the ADCs obtained from the bi-exponential
      fitting function decrease when the diffusion time increases; and (6) both the
      fast and the slow diffusing components of NAA show a considerable restriction by
      what seems to be a non-permeable barrier from which two compartments were
      identified, one having a size of 6-8 microns and the other of approximately 1-2
      microns in size. It seems conceivable that the two populations identified in the
      diffusion experiments represent primarily the NAA in the cell body (soma) and in
      the neurital space (axons and proximal dendrites).

PMID- 9608591
TI  - Stimulus dependence of oxygenation-sensitive MRI responses to sustained visual
      activation.
AB  - Oxygenation-sensitive MRI responses to repetitive and sustained visual activation
      were compared for stimuli with different temporal, spatial, and luminance
      contrasts, i.e. reversing checkerboard, flashing diffuse red light, and
      stationary diffuse gray light with darkness as a control. All paradigms elicited
      an initial oxygenation 'overshoot' as well as a post-stimulus 'undershoot'.
      However, whereas flashing and stationary diffuse light resulted in more than a
      50% decrease of the initial signal response after 6 min of stimulation,
      checkerboard responsed remained largely unaffected (less than 20% signal
      attenuation). The demonstration of a stimulus dependence for sustained visual
      activation reconciles apparently contradictory reports for stimuli involving
      checkerboards as opposed to goggles, flickerlight, and movies. It may be caused
      by stimulus-dependent adjustments of neuronal activity, oxygen consumption, blood
      flow, or blood volume.

PMID- 9608592
TI  - Nuclear magnetic resonance studies of cesium-133 in the halophilic halotolerant
      bacterium Ba1. Chemical shift and transport studies.
AB  - Ba1 bacteria (Halomonas israelensis) were grown on different salt concentrations
      0.2-4 M. When the cells were transferred to a medium containing 25 mM CsCl
      without potassium there was an uptake of cesium by the cells. The intracellular
      cesium signal was shifted from the cesium signal in the medium without the use of
      a shift reagent. The shift was depended on the salt concentration in the growth
      medium. The intracellular cesium shift showed a much smaller dependence on the
      concentration of salts in the medium than the extracellular cesium; the same
      results were detected for cells grown on a medium containing 25 mM CsCl. The
      cesium transport through the cell membrane was mostly by active transport. The
      cesium concentration in the cell was higher than that of the medium,
      approximately 100 mM intracellular concentration compared to 25 mM in the medium.
      The first order constants for influx or efflux of cesium were from 2 x 10(-4) and
      up to 24 x 10(-4)/min for the different medium concentrations.

PMID- 9608593
TI  - Current awareness in NMR in biomedicine.

PMID- 9608594
TI  - Purification of proteins with aqueous two-phase solvent systems by countercurrent
      chromatography.

PMID- 9608595
TI  - Synthesis of heterocyclic beta-aminoalcohol precursors of heterocyclic alpha
      aminoacids.

PMID- 9608596
TI  - Synthesis of heterocyclic alpha-aminoaldehyde and alpha-aminoacid analogues of
      histidine.

PMID- 9608597
TI  - Synthesis of beta-tetrazolyl DL-alanine derivatives.
AB  - Interest in non-natural alpha-amino acids is growing because of their potential
      biological activity. We describe, in this paper, a synthesis of beta-tetrazolyl
      alpha-amino esters by action of 5-aryl tetrazoles, 2, on N-benzyloxycarbonyl di
      dehydro methylalaninate, 3.

PMID- 9608598
TI  - Preparation and properties of the decarboxylated dimer of aminoethylcysteine
      ketimine.

PMID- 9608599
TI  - Lithium and psychosis revisited.
AB  - 1. Using differential response to medications may help in resolving the central
      problem of heterogeneity of the psychoses, 2. A distinct subgroup of patients
      with a lithium responsive, nonaffective psychosis has been shown to have their
      core psychotic (nonaffective) symptoms respond to lithium alone. 3. The family
      histories of patients with lithium responsive, nonaffective psychoses suggests
      that there is less genetic loading for this subgroup of patients. 4. Research on
      the prodromal adjustment of lithium responsive, nonaffective psychosis patients
      has not been reported. 5. Lithium responsive patients showed significantly fewer
      negative symptoms than did those patients with a nonaffective psychosis who did
      not respond to lithium. 6. Patients with lithium responsive, nonaffective
      psychoses showed more extreme in vitro lithium ratios in the red blood cells and
      significantly less of all types of phospholipid methylation. 7. Patients with
      lithium responsive, nonaffective psychoses showed significantly greater reduction
      in symptoms during a physostigmine challenge test, but results from apomorphine
      challenge tests could not be replicated. 8. Aside from differential response to
      lithium, research on difference in treatment response and outcome for this group
      has not been reported. 9. Preliminary evidence may suggest that lithium
      responsive, nonaffective psychosis is a phenocopy of other psychotic disorders
      that is not associated with ventriculomegaly but is associated with stimulant
      abuse. 10. Lithium's effects on acetylcholine as well as effects on dopamine and
      serotonin may explain its efficacy with this subgroup of patients. 11. This
      review supports the existence of a distinct subgroup of patients with
      nonaffective psychoses who may have a separate disorder, but further research is
      necessary. 12. Lithium responsive nonaffective psychosis appears to be a
      separate, distinct psychotic phenocopy.

PMID- 9608600
TI  - Bone density measurement in major depression.
AB  - 1. Disturbances in cortisol secretory patterns and excessive secretion of
      cortisol after a variety of neuroendocrine stimulation tests indicate excessive
      activity of the hypothalamic-pituitary-adrenocortical axis in depression. 2.
      Peripheral indicators of hypercortisolemia have also been observed (e.g. enlarged
      adrenal glands, glucocorticoid insensitivity and insulin intolerance). 3.
      Excessive cortisol production may also result in altered bone metabolism and bone
      architecture, and a recent study by Michelson et al. (1996) found slightly lower
      bone density in depressed women with hypercortisoluria versus healthy controls.
      4. In this study, the authors examined bone mineral density (BMD) using dual
      energy radiographic absorptometry (DEXA) technique in 6 depressed patients (3
      with and 3 without hypercortisoluria) with a mean (+/- SD) age of 41 +/- 13
      years, and in 5 healthy, controls with mean age 38 +/- 4 years). 5. DEXA images
      of the lumbar vertebrae (L1 to L4) for BMD were acquired over a 5-minute
      interval. 6. Overall, the authors observed no difference in mean BMD values
      between patients and controls, nor were differences observed between patients
      with and without hypercortisoluria.

PMID- 9608601
TI  - Attentional effects of single dose triazolam.
AB  - 1. While the effects of benzodiazepines on human memory have been extensively
      studied little is known about the effects of these agents on attentional
      processes. The authors studied the effects of a single dose of triazolam on
      selective visual-spatial attention using a double blind, placebo controlled
      design. 2. In each of 2 sessions 12 normal volunteers ingested either 0.25 mg of
      triazolam or placebo. Attentional performance was evaluated using two versions of
      the covert orienting paradigm which measured automatic (exogenous) and controlled
      (endogenous) aspects of attentional orienting, respectively. 3. Triazolam
      selectively modified performance on automatic orienting to exogenous cues.
      Specifically, triazolam increased the facilitation of target detection seen at
      shorter (150 msec) SOA's. This may indicate an increase in facilitation and a
      reduction in inhibition or a slowing of the time course of the biphasic
      attentional effect normally resulting from exogenous cuing. 4. These results
      indicate the importance of using experimental paradigms which effectively
      dissociate endogenous and exogenous mechanisms of spatial orienting in studies
      evaluating the effects of pharmacological agents on visual-spatial attention.

PMID- 9608602
TI  - Increase in red blood cell triiodothyronine uptake in untreated unipolar major
      depressed patients compared to healthy volunteers.
AB  - 1. Kinetic parameters of red blood cell (RBC) L-triiodothyronine (T3) initial
      uptake (Vmax, maximal velocity and Km, Michaelis constant) were determined in 34
      untreated inpatients suffering from unipolar depression and in 40 healthy
      volunteers. 2. Both Vmax and Km were significantly increased in depressed
      patients as compared to controls. The alterations in kinetic parameters were not
      associated with the severity of depression. 3. Out of the 19 depressed patients
      who were submitted to TRH test, 7 of them (36%) showed a blunted TRH-induced TSH
      response associated with a Vmax situated outside the control mean value +/- 1
      S.D. 4. The authors found a significant positive correlation between Vmax of RBC
      L-T3 and L-tryptophan (TRP) uptakes which is in agreement with the assumption
      that L-T3 and L-TRP share a common carrier system at the erythrocyte level. 5.
      The results indicate that the uptake of L-T3 by RBC is increased in major
      depression. These transport perturbations might reflect alterations in the
      plasmatic metabolism of L-T3. Evaluation of RBC L-T3 uptake could be useful in a
      best biological characterization of the depressed patients with regard to their
      thyroid function.

PMID- 9608603
TI  - Changes of monoamines in post-mortem brains from patients with diffuse Lewy body
      disease.
AB  - 1. In the present study, we measured the concentrations of 5-hydroxytryptamine (5
      HT), norepinephrine and dopamine in post-mortem brains from five patients with
      diffuse Lewy body disease (DLBD), in comparison with five brains from patients
      with Alzheimertype dementia (ATD), and five brains from normal controls. 2. They
      were measured by means of high-performance liquid chromatography fluorometric
      detection. 3. Compared with the ATD and normal control brains, the DLBD ones
      showed decreased concentrations of 5-HT, norepinephrine and dopamine in the
      putamen, and lower 5-HT and norepinephrine concentrations, and almost equal
      dopamine ones in the neocortex.

PMID- 9608604
TI  - Tianeptine therapy for depression in the elderly.
AB  - 1. Depression is frequent in the elderly but difficult both to diagnose and treat
      due to a number of distinctive features. 2. Tianeptine is a novel antidepressant
      with a reverse mode of action to that of the selective serotonin reuptake
      inhibitors yet with proven efficacy and safety. 3. 63 elderly patients (mean
      age:68.8 years; range:65-80 years) with depressive symptoms (major
      depression:55.6%; dysthymia:44.4%) were included in a 3-month open multicenter
      study with tianeptine (25 mg daily). 4. 43 patients (68.2%) completed the study.
      There were no drop-outs due to side-effects. Total Montgomery and Asberg
      Depression Rating Scale scores were significantly decreased (p < 0.01) on day 14,
      with a response rate of 76.7%. 5. Improvements were also observed in anxiety and
      cognitive performance. Side-effects were seen in only 11.7% of patients, with no
      changes in laboratory or ancillary safety parameters. Tianeptine is thus
      effective and well tolerated in this category of patient.

PMID- 9608605
TI  - Effects of pimozide on the psychopathology of delusional disorder.
AB  - 1. The effects of pimozide on the psychopathology of delusional disorder were
      studied. 2. After six weeks, pimozide (2-12 mg/day) administration had no effect
      on the Brief Psychiatric Rating Scale, or in the psychological, social and
      occupational functioning, as measured by the Global Assessment of Functioning
      Scale. 3. When the different dimensions of the delusional experience were looked
      upon, no modifications were observed in any of them after six weeks of pimozide
      treatment. 4. These data failed to support the therapeutic role of pimozide in
      the treatment of delusional disorder and may suggest, when compared to other
      disorders with prominent delusions such as schizophrenia, a different
      neurobiology for the illness.

PMID- 9608606
TI  - Evaluation of efficacies of different classes of antidepressants in the forced
      swimming test in mice at different ages.
AB  - 1. The efficacies of different classes of antidepressants were investigated using
      the forced swimming test with mice at different ages. 2. Imipramine (4-32 mg/kg),
      desipramine (2-16 mg/kg) and bupropion (32, 64 mg/kg) showed activity in all age
      groups. 3. The selective serotonin reuptake inhibitors (SSRIs) citalopram (16 and
      32 mg) and paroxetine (4 and 8 mg) were inactive in the oldest (40 weeks) group
      of mice, despite showing activity at the same doses in mice ranging in age from 4
      24 weeks old. 4. Both SSRIs showed anti-immobility effects at low doses,
      (paroxetine: 1 and 2 mg/kg; citalopram: 4 and 8 mg/kg) in the 40-week old mice.
      These effects were not evident in the three younger groups of mice. 5.
      Moclobemide, a reversible selective inhibitor of monoamine oxidase-A, showed
      activity only at a high dose (128 mg/kg) and only in 12-week old animals. 6.
      Since SSRIs have been reported to have relatively selective effects on 5-HT1B
      receptors, the present results suggest that further studies comparing the
      effectiveness of SSRIs and other antidepressants in elderly patients should be
      done. Studies of the effects of aging on the density and/or affinity of 5-HT1A
      and 5-HT1B/1D receptors are also warranted.

PMID- 9608607
TI  - Mechanism of triazolo-benzodiazepine and benzodiazepine action in anxiety and
      depression: behavioral studies with concomitant in vivo CA1 hippocampal
      norepinephrine and serotonin release detection in the behaving animal.
AB  - 1. Real time, in vivo microvoltammetric studies were performed, using miniature
      carbon-based sensors, to concurrently detect norepinephrine (NE) release and
      serotonin (5-HT) release, in 2 separate electrochemical signals, within CA1
      region of hippocampus in the freely moving and behaving, male, Sprague Dawley
      laboratory rat. 2. Concurrently, four parameters of open-field behavior, i.e.
      Ambulations, Rearing, Fine Movements and Central Ambulatory behavior (a measure
      of anxiety reduction behavior), were assayed by infrared photobeam detection. 3.
      Time course studies showed that the mechanism of action of the
      triazolobenzodiazepine (TBZD), adinazolam, (Deracyn) is dramatically different
      from that of the classical benzodiazepine (BZD), diazepam (Valium, i.e.,
      adinazolam increased, whereas diazepam decreased, 5-HT release within CA1 region
      of hippocampus in the freely moving and behaving rat. 4. Adinazolam initially
      increased NE release and then decreased NE release in CA1 region of hippocampus
      in the freely moving and behaving rat whereas diazepam only decreased the
      electrochemical signal for NE; the decrease in NE produced by adinazolam was
      greater than the decrease in NE release produced by diazepam. 5. The Behavioral
      Activity Patterns, derived from same animal controls, simultaneously with
      detection of in vivo microvoltammetric signals for NE release and 5-HT release,
      showed that the BZD, diazepam, exhibited more potent sedative properties than did
      the TBZD adinazolam. 6. Hippocampal 5-HT and NE release effects of the TBZD,
      adinazolam, concomitant with behavioral effects lends explanation to the dual
      anxiolytic/antidepressant properties of the TBZDs.

PMID- 9608608
TI  - Effects of thioperamide on locomotor activity and on memory processes.
AB  - 1. Rats were tested in an open field. Thioperamide given i.p. 30 minutes before
      the tests produced an increase of locomotor activity at 2 mg/kg and no behavioral
      effect at 5 mg/kg. 2. The repetition of the open field tests caused a reduction
      of ambulation in three successive tests. This effect was increased by
      thioperamide 2 and 5 mg/kg given after the tests, suggesting that this compound
      improved memory consolidation.

PMID- 9608609
TI  - Characterization of desamino-5-[125I]iodo-3-methoxy-zacopride ([125I]MIZAC)
      binding to 5-HT3 receptors in the rat brain.
AB  - 1. Antagonists at 5-HT3 receptors have shown activity in animal models of mental
      illness, however, few radiolabeled 5-HT3 ligands are available for preclinical
      studies. MIZAC, an analogue of the selective 5-HT3 antagonist, zacopride, binds
      with high affinity (1.3-1.5 nM) to CNS 5-HT3 sites. The authors report here the
      selectivity of MIZAC for these sites in rat brain homogenates. 2. Ninety-seven
      percent of total specific binding of [125I]MIZAC (0.1 nM) of was displaced by
      bemesetron (3 microM), a selective 5-HT3 antagonist. Competition studies using
      ligands with known affinities for 5-HT3 sites give a high correlation with
      reported pKi values (r2 0.98). Bemesetron displaceable binding has a regional
      distribution consistent with that of the 5-HT3 receptor, i.e. highest in cortex
      and hippocampus, and lowest in striatum and cerebellum. 3. Potent antagonists
      present at concentrations sufficient to occupy 95% of other 5-HT receptor
      populations (1A, 1B, 1D, 2A, 2B, 2C, 5A, 5B, 6, and 7) showed minimal ability to
      displace [125I]MIZAC binding (3 nM). Specificity studies using radioligand
      binding assays selective for 5-HT4, 5-HT6, and 5-HT7 receptors, and for binding
      sites of other neurotransmitters indicate a high degree of selectivity of
      [125I]MIZAC for the 5-HT3 receptor. 4. [125I]MIZAC binds to an apparent low
      affinity (benzac) site having a unique pharmacology. Low affinity binding was
      displaceable by benztropine, but not by other muscarinic agents nor inhibitors of
      dopamine uptake. The regional distribution of the low affinity site differed
      markedly from that of the high affinity site. The apparent affinity of
      [125I]MIZAC for the benzac site is two orders of magnitude lower than for the 5
      HT3 receptor. Given its high selectivity for 5-HT3 binding sites, [125I]MIZAC
      appears to be a promising ligand for labeling 5-HT3 receptors in vitro and in
      vivo.

PMID- 9608610
TI  - Effect of exercise training and chronic ethanol ingestion on cholinesterase
      activity and lipid peroxidation in blood and brain regions of rat.
AB  - 1. This study examines the effects of exercise training and chronic ethanol
      consumption on cholinesterase activity and its relationship to lipid peroxidation
      in blood and brain regions of rat. 2. Exercise training (6.5 weeks) decreased
      acetylcholinesterase (AChE) activity significantly (64% of control) in
      hypothalamus and increased AChE activity in cerebral cortex (149% of control),
      whereas, malondialdehyde (MDA) levels increased in hypothalamus (129% of control)
      and decreased in cortex, striatum, and cerebellum (50%, 69% and 75% of control),
      respectively. 3. Chronic ethanol ingestion (2.0 gm/kg, p.o. for 6.5 weeks)
      significantly increased butyrylcholinesterase (BuChE) activity in plasma (136% of
      control) and decreased AChE activity in hypothalamus (63% of control), whereas,
      MDA levels increased in hypothalamus, cortex, and plasma (140%, 130% and 220% of
      control), respectively. 4. The combination significantly increased BuChE activity
      (173% of control) in plasma and decreased AChE activity (71% of control) in
      hypothalamus and (57% of control) in cerebellum, whereas, MDA levels increased in
      hypothalamus, cerebellum, medulla and plasma (134%, 128%, 140% and 309% of
      control), respectively. 5. Exercise training, chronic ethanol ingestion, and
      combination selectively inhibited hypothalamic AChE and the inhibition was
      correlated with increased lipid peroxidation (r = 0.11, 0.41 and 0.45) which may
      perturb hypothalamic function. The combination enhanced the peripheral stress
      response by increasing plasma BuChE activity and lipid peroxidation.

PMID- 9608611
TI  - Evidence suggesting that gonadal hormones influence benzodiazepine withdrawal
      induced weight loss in rats.
AB  - 1. In experimental animals, benzodiazepine (BZ) withdrawal syndrome includes
      anorexia and acute weight loss. The literature shows several sex-based
      differences in the expression of BZ dependence; however, the authors did not find
      studies dealing with the influence of gonadal hormones on BZ withdrawal-induced
      weight loss. Thus, this study was designed to investigate the effects of
      castration on diazepam (DZ) withdrawal-induced weight loss in rats. 2. Male (260
      330 g) or female (220-260 g) Wistar rats were anesthetized with ether and
      submitted to surgical castration or sham-operation. Seven days later, recovered
      from the surgery, the animals were injected i.p. with DZ (4 mg kg-1 day-1) or
      appropriate vehicle (VEH; 2 ml kg-1 kg-1 day-1) for 28 days. In the next 7 days,
      the rats received the same doses of DZ (four groups) or VEH (eight groups).
      Weights of all animals were recorded daily to the nearest gram at 09:00 h. To
      assess the degree of weight loss and make statistical comparisons, weights over
      days 29-34 were expressed as percentage of those recorded in the morning of day
      28. 3. Sham-operated female rats from the group DZ-VEH showed a small but
      statistically significant weight loss on days 29 and 30 (P < 0.05) when compared
      with groups VEH-VEH and DZ-DZ. Ovariectomized rats, however, did not show any
      significant change in body weight from days 29-34. 4. Sham-operated male rats did
      not exhibit any significant weight loss after DZ withdrawal. Orchidectomized
      animals, however, showed a small but statistically significant weight loss on day
      31 (P < 0.05) when compared with groups VEH-VEH and DZ-DZ. 5. These results show
      a gonadal influence on DZ withdrawal-induced weight loss in Wistar rats; in
      particular, they also suggest that female hormones (progesterone and/or estrogen)
      facilitate whilst male hormones inhibit this phenomenon.

PMID- 9608612
TI  - Single and repeated electroconvulsive shocks activate dopaminergic and 5
      hydroxytryptaminergic neurotransmission in the frontal cortex of rats.
AB  - 1. The effect of electroconvulsive shock (ECS) on the extracellular concentration
      of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and
      5-hydroxyindoleacetic acid (5-HIAA) was examined in the frontal cortex of rats
      with the use of in vivo microdialysis. 2. The extracellular concentration of
      DOPAC, HVA and 5-HIAA was largely increased after the first ECS treatment. The
      increase after the eighth ECS treatment tended to be attenuated or was
      significantly attenuated as compared to that after the first ECS treatment. The
      baseline concentration of DOPAC and 5-HIAA was significantly increased after
      repeated ECS, though that of DA and HVA did not show any significant change after
      repeated ECS. 3. These results suggest that the activating effect of repeated ECT
      on 5-hydroxytryptaminergic (5-HT) and DA neurotransmission, (especially on 5-HT
      neurotransmission), is significant in improving depression both in patients with
      Parkinson's disease (PD) and in those who do not suffer from PD.

PMID- 9608613
TI  - Pointers and pitfalls in the neurologic examination.
AB  - The neurologic examination is reviewed with regard to efficiency, technical
      errors, and patient comfort. Misleading nomenclature causes errors in executing
      and interpreting many bedside tests. The examiner can insure success by accepting
      every patient nonjudgmentally and by maintaining a mind-set that expects to find
      abnormalities. Since the examiner cannot do every possible test on every patient,
      intelligent utilization of the history may shorten the examination yet make it
      more informative. To insure full patient cooperation, the examiner should make
      each step in the examination into a game or contest and, wherever possible, match
      functions, such as muscle-to-muscle strength testing, directly against the
      patient's.

PMID- 9608614
TI  - Augenblickdiagnose.
AB  - The process of making a diagnosis is integral to the practice of medicine, but
      diagnostic reasoning is rarely taught as a specific point. In most instances,
      experienced clinicians use a method of generating and testing hypotheses, finally
      selecting the hypothesis that best explains the clinical picture. Occasionally,
      especially distinctive physical signs allow augenblickdiagnose, a term that means
      "diagnosis in the blink of an eye." The process is too rapid to have followed a
      hypothesis testing method. Similarly, key fragments of history often permit very
      rapid diagnosis. The ability to make a snap diagnosis based on characteristic
      physical signs or snippets of clinical information relies on familiarity with
      certain critical clinical information. The reader is invited to try to
      augenblickdiagnose several cases.

PMID- 9608615
TI  - Sensory mononeuropathies.
AB  - The clinical neurologist frequently encounters patients with a variety of focal
      sensory symptoms and signs. This article reviews the clinical features,
      etiologies, laboratory findings, and management of the common sensory
      mononeuropathies including meralgia paresthetica, cheiralgia paresthetica,
      notalgia paresthetica, gonyalgia paresthetica, digitalgia paresthetica,
      intercostal neuropathy, and mental neuropathy.

PMID- 9608616
TI  - Pearls and pitfalls in the diagnosis and management of central nervous system
      infectious diseases.
AB  - Laboratory techniques for the diagnosis of central nervous system (CNS)
      infections are rapidly improving but at present have limitations that necessitate
      our guarded enthusiasm. Enteroviruses are the most common infectious agents of
      viral meningitis for which an etiology can be determined, and it is anticipated
      that the use of the reverse transcriptase polymerase chain reaction (RT-PCR)
      technique should significantly improve the identification of the etiologic agent
      of aseptic meningitis. The combination of the polymerase chain reaction technique
      with laboratory methods for the determination of intrathecal antibody production
      to herpes simplex virus and varicella-zoster virus have improved the rapidity
      with which these viral infections can be diagnosed. The pearls and pitfalls of
      the use of these laboratory techniques in the diagnosis of viral meningitis,
      recurrent meningitis, and focal encephalitis are included. Recommendations for
      the empiric therapy of bacterial meningitis in children and adults have changed
      because of the emergence of penicillin and cephalosporin-resistant pneumococcal
      organisms. The currently recommended antibiotics and their dosages are included.
      The evidence for the efficacy of dexamethasone therapy in bacterial meningitis is
      provided. Meningitis due to Mycobacterium tuberculosis is increasingly
      recognized, and the initiation of empiric antituberculous chemotherapy should not
      await the results of CSF cultures. Toxoplasma encephalitis and primary CNS
      lymphoma are the most common cause of mass lesions in patients with HIV, and the
      diagnostic techniques to distinguish between these two infections is reviewed. A
      short discussion of the best test for the diagnosis of neurosyphilis is provided.

PMID- 9608617
TI  - Perils and pointers in the evaluation and management of back pain.
AB  - This article examines the current treatment of low back pain in light of the
      recent Agency for Health Care Practice and Research (AHCPR) guidelines on the
      acute management of low back pain (the AHCPR is an agency of the federal
      government). The article describes the most important history questions, the most
      helpful physical signs, and the most practical examination techniques.
      Considerable emphasis is placed on ruling out the "red flag" diagnoses that
      require immediate treatment. The article agrees with the AHCPR that if the red
      flags of cancer, infection, fracture, and neurologic deficit are ruled out, most
      of the remaining causes of acute back pain are largely self-healing over 4-8
      weeks. Emphasis is placed on using the history and physical examination rather
      than expensive studies to rule out the red flag cases, so that cost-effective
      management of low back pain is possible. The author also reviews the ten top
      causes of low back pain and their evaluation and treatment.

PMID- 9608618
TI  - Approach to patients with inherited neurologic disorders.
AB  - There have been tremendous advances in our understanding of inherited neurologic
      disorders. It is important to recognize that genetic factors contribute to common
      neurologic disorders once considered idiopathic. Diagnosing and counseling
      individuals with inherited neurologic disorders requires understanding of
      fundamental genetic principles. The essential approach to such patients and their
      family members is presented.

PMID- 9608620
TI  - Chronic fatigue syndrome: a review for clinicians.
AB  - Syndromes characterized by persistent fatigue, musculoskeletal pain, sleep
      disturbance, and subjective cognitive impairment have been common problems in
      clinical practice for decades. The chronic fatigue syndrome case definition was
      created to standardize the patient population in research studies and to foster a
      systematic and comprehensive approach to the attempt to define the etiology and
      pathophysiology of these syndromes. The pathogenesis of chronic fatigue syndrome
      remains unknown, though it does appear to be associated with subtle
      neuroendocrine and immunologic abnormalities. Treatment of chronic fatigue
      syndrome is empirical. Significant palliation is often possible, though treatment
      success requires skillful practice of the art of medicine.

PMID- 9608619
TI  - Pearls and pitfalls in clinical neuroradiology.
AB  - Imaging technology continues to advance at a rapid pace. Central nervous system
      imaging, in particular, is an invaluable tool for the practicing clinical
      neurologist. Although computed tomography (CT) was once the procedure of choice
      for neuroimaging, CT has been surpassed by magnetic resonance imaging (MRI)
      because of the latter's greater sensitivity. MRI exquisitely demonstrates brain
      and spine pathology by means of its multiplanar capability and its ability to
      generate different tissue contrast with various pulse sequences. However,
      artifacts as well as normal anatomic variants can mimic significant CNS
      pathology. An understanding of the technology involved in producing and
      interpreting these images is necessary in order that protocols can be tailored
      for each individual patient and that unimportant findings are not misinterpreted
      as being pathologic. This article will present cases illustrating some of the
      common neuroimaging artifacts and normal variants as well as important
      differential diagnoses of certain imaging findings.

PMID- 9608621
TI  - Pearls in neurodermatology.
AB  - Many diseases present with both neurologic and dermatologic manifestations. Eight
      such clinical cases are presented, along with clinical photographs of the skin
      lesions, in the format of a self-evaluation. Each case is followed by a
      discussion and a brief review of the characteristic cutaneous and neurologic
      findings. The intent is to demonstrate classic dermatologic manifestations of
      diseases seen by neurologists.

PMID- 9608622
TI  - Pitfalls in the management of patients with malignant gliomas.
AB  - Neurooncology requires the integration of the clinical history, physical
      examination, neuroimaging studies, neuropathology, surgery, radiation therapy,
      and chemotherapy in order to properly diagnose and treat patients with suspected
      brain tumors. The review herein serves to illustrate and emphasize the pitfalls
      that can potentially occur during each step of the process of managing patients
      with malignant gliomas. Familiarity with these pitfalls will enhance the
      neurologist's ability to successfully manage patients with neurooncological
      disease.

PMID- 9608623
TI  - Pearls and pitfalls in the horror cinema.
AB  - Observations on the neurologic signs and symptoms of Count Dracula, Wolfman, and
      Frankenstein's Monster are presented as viewed by a specialist in neuromuscular
      disease. Key clinical features of these horror movie figures illustrate a variety
      of pearls in the diagnosis of a variety of neurologic disorders, including
      porphyria, lead poisoning, osteosclerotic myeloma, and myasthenia gravis.

PMID- 9608624
TI  - Effects of adenosine on cholinergic transmission in mammalian vesical
      parasympathetic ganglia.
AB  - Intracellular recordings were made from mammalian vesical parasympathetic
      ganglia. A fast excitatory postsynaptic potential (EPSP) was abolished by
      hexamethonium (200 microM) in rabbit and feline ganglia. A slow inhibitory
      postsynaptic potential (IPSP) and a following slow EPSP were abolished by
      atropine (1 microM) in the feline ganglia. Bath application of adenosine (300
      microM) depressed the amplitude of nicotinic fast EPSP by 48 +/- 4% in the rabbit
      ganglia. The action of adenosine was dose-dependent. An antagonist of A1
      purinoceptors, 8-cyclopentyltheophylline (1-10 microM), inhibited the adenosine
      induced depression but not the amplitude of fast EPSP. Adenosine (2-3 mM) did not
      significantly affect either the muscarinic slow IPSP, or the slow EPSP, in the
      feline ganglia. Adenosine also caused a hyperpolarization (1-5 mV) in 40% of the
      rabbit neurons and 66% of the feline neurons. However a purinergic IPSP was not
      recorded from either species. These data suggest diverse actions of adenosine in
      modulating cholinergic transmission in rabbit and feline vesical ganglia.

PMID- 9608625
TI  - Serologic survey for HTLV-I in Kanagawa Prefecture.
AB  - To investigate the seroprevalence of HTLV-I in Kanagawa Prefecture (central
      Japan), we tested the sera of 8,264 healthy volunteers and 2,414 pregnant women.
      Of the 8,264 healthy volunteers, 66 (0.80%) were seropositive. The seroprevalence
      of HTLV-I in the pregnant women was 14/2,414 (0.58%), and this rate was almost
      identical to that in the healthy female volunteers 15 to 44 years of age (0.59%).
      These figures indicate that the seroprevalence of HTLV-I in Kanagawa Prefecture
      is very low and that sexual contact may not be an important contributory factor.

PMID- 9608626
TI  - The callotasis method of limb lengthening.
AB  - Limb lengthening by the callotasis technique of De Bastiani and use of the
      Orthofix external fixator was performed on 25 femurs and tibias of 23 patients
      between June 1989 and March 1995 in our clinic. Twenty femoral and five tibial
      segments were lengthened. Simultaneous lengthening of the femur and tibia was
      performed in two limbs. The mean duration of follow-up was 35.4 months (range, 12
      to 81 months). Age at surgery ranged from 9 to 25 years (16.4 years on average).
      Poliomyelitis was the most common cause (69.6%) of the leg length discrepancy.
      The maximal achieved lengthening was 8 cm and the shortest 4 cm, with an average
      of 5.11 cm (13.6% of original bone length). The mean healing index was 38.6
      days/cm; the complication rate was 36%. We conclude that limb lengthening by the
      De Bastiani method is a satisfactory procedure for pediatric and adult patients
      with moderate limb-length discrepancies.

PMID- 9608627
TI  - A study of 46 cumulative breast cancer autopsy cases.
AB  - Forty-six cases of breast cancer, autopsied at the Tokai University Hospital,
      between 1975 and 1993, were studied. Forty of the patients had undergone surgery,
      and 27 of them had been surgically treated in the Tokai University Hospital. The
      major causes of death were respiratory failure, cancer-related complications, and
      hepatic failure. Frequently involved organs were lymph node, lung, liver, and
      bone. The survival time after surgery ranged from 1 day to 137 months, with the
      patients being divided into two groups based on survival of more or less than
      three years after surgery. Frequently observed in individuals surviving less than
      3 years were larger tumor sizes, extensive lymph node metastases, advanced
      stages, and negative reactions for estrogen and progesterone receptors, as
      compared to individuals surviving for more than 3 years. The patterns of tumor
      metastasis were also different in two groups. Local recurrences were more
      frequently observed in short-term survivors whereas disseminated spreading was
      encountered in the long-term survivors. These findings seem to indicate that not
      only survival time but also pattern of recurrence are related to the status of
      the original tumor.

PMID- 9608628
TI  - Dependence of transverse relaxation time T2 of biologic tissues on the interpulse
      delay time in Carr-Purcell-Meiboom-Gill (CPMG) measurements.
AB  - To determine the transverse relaxation time (T2) of biological tissues in nuclear
      magnetic resonance measurements, the Carr-Purcell-Meiboom-Gill (CPMG) method has
      been recommended to avoid the effect of external magnetic field inhomogeneity on
      T2 values. However, a dependence of T2 on the interpulse delay time (IPDT) in the
      CPMG measurements has been shown for biological tissues. The present study
      examined the dependence of the T2 on IPDT for muscle, lung (passively collapsed
      or degassed), and brain tissues. It was found that the CPMG T2 of the lung was
      strongly dependent upon the IPDT, in contrast to muscle and brain tissues. The
      IPDT dependence of the CPMG T2 for lung tissue, which was lessened by degassing,
      was affected by the magnetic field inhomogeneity due to air-tissue interfaces,
      but not by the spin-locking effect, since the T2 measured by the Carr-Purcell
      Freeman-Hill (CPFH) method did not show this dependence. These results should aid
      in the evaluation of T2 values for biological tissues measured under various
      conditions and by different techniques.

PMID- 9608629
TI  - Alterations in glutathione peroxidase activity following reperfusion injury to
      rat liver.
AB  - Prevention of cellular damage after warm ischemia is of major importance in liver
      transplantation. In this study, we determined the extent to which lipid peroxides
      contribute to the pathogenesis of hepatic cell damage induced by transient warm
      ischemia with subsequent reperfusion. In addition, the function and
      immunohistochemical features of glutathione peroxidase, a potent physiological
      lipid peroxide scavenger of the liver, was assessed. Reperfusion following 15 or
      30 minutes of warm ischemia resulted in a significant elevation in serum and
      liver lipid peroxidase (LPO) levels. In addition, necrosis of the hepatic
      periportal area accompanied with remarkable rises in serum aspartate
      aminotransferase (AST) and alanine aminotransferase (ALT) were observed. In
      contrast, 30 min of ischemia without reperfusion caused minimal hepatocellular
      damage. The adverse changes after ischemia/reperfusion were minimized by
      pretreatment with superoxide dismutase (SOD). These results indicate that
      increased lipid peroxidation by production of radicals after reperfusion caused
      the liver cell damage. After ischemia/reperfusion, liver glutathione peroxidase
      (GSH-PO) activity was significantly decreased and its location altered in the
      damaged liver. These findings suggest that GSH-PO contributes significantly to
      the protection against hepatic reperfusion injuries.

PMID- 9608630
TI  - Convulsions in hemodialysis (HD) patients with elevated polymorphonuclear
      leukocyte elastase (PMNE) levels.
AB  - Eight hemodialysis (HD) patients with convulsions of unknown cause were monitored
      for serum levels of uremic toxins such as methylguanidine(MG), and
      polymorphonuclear leukocyte elastase (PMNE). Twenty HD patients without
      convulsions served as controls. In the convulsion group, MG and PMNE were high.
      In 2 patients, convulsions subsided after daily hemodiafiltration (HDF). Although
      PMNE was thought to be a mediator of injury in the present series, no significant
      correlation was found between PMNE and either neutrophil numbers or endotoxin
      levels. PMNE may indicate the over production of cytokines not associated with
      serious infection or septicemia. In patients with renal failure and complications
      of unknown cause, intensified dialysis therapy such as frequent HDF may be useful
      when combined with treatment of the underlying disease producing the toxins. PMNE
      measurement is useful in assessing the uremia caused by high cytokine levels and,
      together with methylguanidin (MG) serum levels, can indicate the severity of the
      convulsion.

PMID- 9608631
TI  - Analysis of factors causing signal loss in the measurement of lung tissue water
      by nuclear magnetic resonance.
AB  - The water content of lung, brain, and muscle tissue was measured by nuclear
      magnetic resonance (NMR) and compared with gravimetric determinations. The NMR
      signal intensity of water was measured by a single 90 degree pulse and by a spin
      echo sequence. The absolute water content was determined by the difference in the
      sample's weight before and after desiccation. The NMR detectable water in each
      tissue was expressed as a percentage of the signal intensity for an equal weight
      of distilled water. Using the single pulse measurement, 67% of the
      gravimetrically-measured water was detected in collapsed lung samples (consisting
      of about 47% retained air), in contrast to 96% for brain and 98% for muscle. For
      degassed lung samples, the NMR detectability of water increased to 87% with the
      single pulse measurement and to 90% with the spin-echo measurement, but the
      values remained significantly less than those of brain or muscle. Factors that
      caused the NMR signal loss of 33% in collapsed lung samples were: air-tissue
      interfaces (20%), microscopic field inhomogeneity (3%), and a water component
      with an extremely short magnetization decay time constant (10%).

PMID- 9608632
TI  - The role of histamine in ethanol-induced gastric mucosal injury in the rat.
AB  - It has been suggested that changes in the micro circulatory system are related to
      the early production of acute gastric mucosal injury and inflammatory factors
      such as prostaglandins, histamine, etc., have been considered as contributing to
      the development of the injury. We assessed the permeability of the gastric mucosa
      in rats with ethanol-induced acute mucosal injury by measuring the leakage rate
      of 51chronium-ethylene-diamine-tetraacetic acid (51Cr-EDTA) into the gastric
      juice. Histamine concentrations in the gastric mucosa was measured by high
      performance liquid chromatography. The enterochromaffin-like (ECL) cell counts in
      the gastric mucosa was performed following histamine staining with an enzyme
      labeled antibody, and the histamine released due to degranulation was observed.
      We also investigated the kinetics of endogenous histamine in the gastric mucosa.
      Five minutes after the administration of ethanol, an increase in permeability, an
      increase in histamine concentration, and a decrease in ECL cell count were found
      in the gastric mucosa. These results suggest that endogenous histamine in the
      gastric mucosa is closely related to the early development of acute gastric
      mucosal injury.

PMID- 9608633
TI  - A case of epithelioid hemangioendothelioma associated with an artery.
AB  - We report a case of epithelioid hemangioendothelioma (EHE) arising in the left
      elbow of a 67-year-old woman. The tumor was characterized by centrifugal growth
      and association with the brachial artery, causing complete occlusion.
      Immunohestochemical and electron microscopical features were typical of EHE. The
      patient was free of local recurrence or disease metastasis for more than 3 years
      after tumor resection, but subsequently died of respiratory failure due to a
      primary lung cancer.

PMID- 9608634
TI  - PUVA treatment of human keratinocytes suppresses the surface expression of
      intercellular adhesion molecule 1 (ICAM-1) and inhibits adherence of PHA-blasts
      in vitro.
AB  - To determine the basis of the therapeutic efficacy of Psoralens and UVA (PUVA) in
      inflammatory skin diseases, the effect of PUVA on the expression of cell adhesion
      molecules of keratinocytes was investigated in vitro. The addition of IFN-gamma
      and TNF-alpha to human keratinocytes in culture up-regulated the expression of
      ICAM-1 and HLA-DR on the cell surface. The cultured human keratinocytes were
      exposed to UVA light in the presence of 8-methoxypsoralen (PUVA). The ICAM-1 and
      HLA-DR surface molecules were stained by monoclonal antibodies, and the intensity
      of the resultant fluorescence was analyzed by FACS-can. PUVA treatment suppressed
      the expression of these cell surface molecules, with increasing UVA fluence.
      Moreover, PHA-blasts failed to adhere to PUVA treated keratinocytes. When
      keratinocytes were treated with PUVA prior to the addition of IFN-gamma and TNF
      alpha, ICAM-1 and HLA-DR expression was suppressed. These results suggest that
      one of the therapeutic mechanisms of PUVA in inflammatory skin diseases is by
      inhibition of the adhesion of activated lymphocytes to keratinocytes due to
      suppression of cell surface molecules. It also suggests that PUVA may be useful
      as maintenance therapy for inflammatory skin diseases.

PMID- 9608635
TI  - A review of chronic inhalation studies with mainstream cigarette smoke in rats
      and mice.
AB  - In this paper, I review the results of a representative selection of chronic
      inhalation studies with rats and mice exposed to mainstream cigarette smoke and
      describe the inhalation exposures and the histopathological changes reported by
      various authors. Many of the studies used nose-only exposure systems, whereas
      others simply used large whole-body chambers. Smoke-induced epithelial
      hypertrophy, hyperplasia, and squamous metaplasia were reported in the conducting
      airways in most of the studies, along with increased numbers of intra-alveolar
      macrophages that were occasionally associated with alveolar metaplasia. Lung
      adenomas and adenocarcinomas were reported in only a few of the studies. No
      statistically significant increase in the incidence of malignant lung tumors was
      seen in either species as a result of smoke exposure, a finding that does not
      agree with the results of epidemiological studies in humans. Possible reasons for
      this lack of correlation are given.

PMID- 9608636
TI  - Precision in data acquisition and reporting of organ weights in rats and mice.

PMID- 9608637
TI  - Appropriate parameters to be tested in rodent oncogenicity studies.

PMID- 9608638
TI  - Precision of organ and body weight data: additional perspective.

PMID- 9608639
TI  - Cytokeratin expression patterns in the rat respiratory tract as markers of
      epithelial differentiation in inhalation toxicology. I. Determination of normal
      cytokeratin expression patterns in nose, larynx, trachea, and lung.
AB  - Cytokeratin (CK) polypeptides constitute the intermediate filament cytoskeleton
      of epithelial cells. The patterns of CK expression can be regarded as specific
      markers for the epithelial differentiation status. Our objective was to map the
      cell type-specific CK expression patterns at all representative sites of the
      respiratory tract of untreated rats to use as a base for the detection of
      inhalation exposure-related differentiation changes. Using routine paraffin
      embedded sections and a panel of well-characterized monoclonal antibodies for
      immunohistochemistry, we obtained CK staining patterns as follows. Nasal cavity:
      respiratory epithelium CK18, CK19 (basal, ciliated, nonciliated cells), CK14,
      and/or CK15 (basal and nonciliated cells); olfactory epithelium CK18 (basal, mid,
      apical zones and Bowman's glands), CK14, and CK15 (basal zone); squamous
      epithelium of ventral meatus CK14, CK15 (basal and suprabasal cells), CK1, 10/11,
      and CK13 (suprabasal cells); glands and columnar epithelia of vomeronasal organ
      and nasolacrimal duct CK7 and CK13 in addition to respiratory epithelial CK
      pattern. Trachea: similar to nasal respiratory epithelium with pronounced CK15
      and additional CK7. Larynx: CK14, CK15 (basal, ciliated, nonciliated cells), CK8,
      CK18, CK19 (not in basal cells), CK4, and CK13 (cuboidal and squamoid cells of
      ventral half). Lung: bronchial epithelium CK14 and CK15 (basal cells only);
      bronchial and alveolar epithelium CK7, CK8, CK18, and CK19; bronchiolar
      epithelium similar but less CK8 and no CK7; pleural mesothelium CK7, CK8, and
      CK19. This inventory of complex CK expression patterns provides the basis for
      investigating test substance-related effects in inhalation toxicology, e.g.,
      cigarette smoke-induced changes.

PMID- 9608640
TI  - Cytokeratin expression patterns in the rat respiratory tract as markers of
      epithelial differentiation in inhalation toxicology. II. Changes in cytokeratin
      expression patterns following 8-day exposure to room-aged cigarette sidestream
      smoke.
AB  - The expression of specific cytokeratin (CK) polypeptide patterns is a sensitive
      marker of the cytoskeletal differentiation of epithelial cells. We developed an
      immunohistochemical method to assess CK expression patterns in the rat
      respiratory tract using serial paraffin-embedded sections from the nasal cavity,
      trachea, and lung. In the present study, this method was used to detect exposure
      related differences in CK expression patterns in adult Wistar rats following
      inhalation of room-aged sidestream smoke (11 mg total particulate matter/m3 air,
      8 days, 12 hr/day, whole body). In the anterior nasal cavity level 1 (NL1),
      changes in CK expression patterns were observed in the respiratory epithelium of
      the lateral wall and the maxilloturbinate (CK14, CK15, and CK18) and in the
      squamous epithelium of the ventral meatus (CK13). At nasal cavity level 2 (NL2),
      immediately behind NL1, changes were observed in the olfactory epithelium (CK13,
      CK14, and CK18) and in the respiratory epithelium of the septum (CK7 and CK19),
      the lateral wall (CK7 and CK13), and the lateral aspect of the maxilloturbinate
      (CK14). Changes were also observed in the submucosal glands, nasolacrimal duct,
      and vomeronasal organ. In the trachea only CK7 expression changed, and in the
      lung expression of CK7 (bronchioli) and CK8 (bronchus) changed; the expression of
      other CK polypeptides did not change. The observed changes in CK expression at
      NL1 correlated with the histomorphological changes, whereas CK expression changes
      were also seen in the olfactory and respiratory epithelia at NL2 and in the
      trachea and lung, where no histomorphological changes were seen. These findings
      indicate that changes in CK expression in respiratory tract epithelial cells are
      a sensitive marker for cellular stress response.

PMID- 9608641
TI  - Effect of hexachloro-1,3-butadiene on renal carcinogenesis in male rats
      pretreated with N-ethyl-N-hydroxyethylnitrosamine.
AB  - Hexachloro-1,3-butadiene (HCBD) is a potent nephrotoxicant that selectively
      damages the straight portion (pars recta) of the proximal tubule in the rat. To
      determine its effects on carcinogenesis. HCBD was administered for 30 wk at a
      concentration of 0.1% by weight in basal diet to male Wistar rats previously
      given 0.1% N-ethyl-N-hydroxyethylnitrosamine (EHEN) in the drinking water for 2
      wk. The combined treatment resulted in a significantly higher incidence of renal
      cell tumors than when EHEN was administered alone. This chronic exposure and a
      short course of a 0.2% HCBD diet for 3 wk caused marked increase in the numbers
      of bromodeoxyuridine-incorporating cells or proliferating cell nuclear antigen
      positive cells in the outer stripe of the kidney. The ability of HCBD to promote
      EHEN-initiated renal tumorigenesis in rats thus appears to be associated
      intimately with linked nephropathy and subsequent cell proliferation.

PMID- 9608642
TI  - Predominant p53 G-->A transition mutation and enhanced cell proliferation in
      uterine sarcomas of CBA mice treated with 1,2-dimethylhydrazine.
AB  - Mouse uterine tumors were examined for genetic alterations in the ras proto
      oncogene and p53 tumor suppressor gene and for other biologically relevant
      immunohistochemical markers that may increase our understanding of the events
      that occur in uterine cancer. Fourteen dimethylhydrazine (DMH)-induced uterine
      sarcomas, including 3 primary malignant fibrous histiocytomas (MFH), 7
      transplanted MFH, 3 stromal sarcomas, and 1 undifferentiated sarcoma, were first
      screened by immunohistochemistry for p53 missense mutations, followed by single
      strand conformation polymorphism analysis and DNA sequencing for the
      identification of point mutations. There was 100% correlation between p53 protein
      immunopositivity and subsequent detection of p53 mutations in DMH-induced
      malignant fibrous histiocytomas. All MFH had a characteristic p53 G:C-->A:T
      transition mutation, consistent with O6-methylguanine mispairing with thymine,
      the most common DNA lesion caused by alkylating agents. DMH-induced uterine MFH
      with p53 mutations also had a higher proliferative rate (qualitatively evaluated
      by immunohistochemical detection of proliferating cell nuclear antigen) when
      compared with other DMH-induced sarcomas. Uterine sarcomas were further evaluated
      for biological end points, such as estrogen receptor and desmin. Neoplastic cells
      from stromal sarcomas (SS), undifferentiated sarcomas (US), and MFH did not stain
      for desmin. The estrogen receptor was detected in normal uteri and a small
      portion of MFH, SS, and US. Our data suggest that DMH-induced uterine sarcomas
      are not consistent with smooth muscle cell origin and that a subset of these
      tumors, specifically DMH-induced malignant fibrous histiocytomas, have unique p53
      G:C-->A:T transitions and a high proliferative rate.

PMID- 9608643
TI  - Arteriopathy induced by an adenosine agonist-antihypertensive in monkeys.
AB  - An adenosine agonist, designated chemically as (R)-N-(2,3-dihydro-1H-inden-1-yl)
      adenosine or CI-947, was administered orally to 2 males and 2 female cynomolgus
      monkeys each at 5, 10, 20, and 50 mg/kg of body weight for 2 wk. One male and 1
      female given 50 mg/kg were euthanatized on days 10 and 8, respectively, because
      of poor clinical condition. Emesis was present at 10, 20, and 50 mg/kg. Decreased
      heart rate and QT prolongation were present at 50 mg/kg. Extramural coronary
      arterial lesions consisting of medial necrosis with cellular debris and mixed
      inflammatory cell response in the intima, media, and adventitia were present in 1
      male at 20 mg/kg and 1 male at 50 mg/kg at study termination. Similar arterial
      lesions were present in the small and large intestines and testis of the male at
      50 mg/kg. Colonic mucosal erosions with mixed inflammatory cell infiltrates in
      the lamina propria were seen in this male and in all CI-947 treated females at
      10, 20, and 50 mg/kg. Myocardial degeneration and necrosis of myocardial fibers
      with mononuclear cell infiltrates in the interstititum were noted in the left
      ventricle of 1 female at 20 mg/kg and in all animals at 50 mg/kg. Renal cortical
      tubular dilatation with increases in serum creatinine and/or blood urea nitrogen
      were noted in a control female and animals at 10 and 50 mg/kg. Plasma CI-947
      concentration increased with increasing dose. Coronary vascular injury in the
      monkey was similar to the arterial lesion in CI-947-treated dogs and may relate
      to the pharmacologic/hemodynamic effects induced by CI-947. When compared with
      the dog, the monkey appears to be less sensitive to development of arteriopathy,
      as indicated by lower incidence, at similar systemic exposure levels.

PMID- 9608644
TI  - Exploration of the transformation potential of a unique male rat protein alpha2u
      globulin using hamster embryonic cells.
AB  - Several environmentally and socially important chemicals such as d-limonene and
      unleaded gasoline have been demonstrated to induce alpha2u-globulin (alpha 2u)
      nephropathy in male rats. Substantial progress has been made in characterizing
      the biological effects of these chemicals on the kidney and in further defining
      prerequisite events in the pathogenesis of this syndrome. The alpha 2u increase
      in the kidney is hypothesized to be the proximal event in the toxicologic and
      tumorigenic sequelae associated with administration of these xenobiotics over the
      male rat's lifetime rather than a direct effect of the administered chemical. The
      administered chemical appears to simply mediate the increase in alpha 2u
      concentration in the kidney. To further investigate the properties of alpha 2u,
      this protein was tested in the pH 6.7 Syrian hamster embryo (SHE) cell
      transformation assay. The alpha 2u caused morphological transformation in these
      cells, whereas another protein, bovine serum albumin, did not induce
      transformation at equimolar concentrations, suggesting a protein-specific
      phenomenon. Neither d-limonene nor trimethylpentane (a causal component in
      unleaded gasoline) induced SHE cell transformation. These results support the
      hypothesis that alpha 2u increase in proximal convoluted tubules may directly
      cause renal tumorigenesis in male rats. The SHE cell transformation assay may be
      a useful tool for mechanistic studies of this syndrome.

PMID- 9608645
TI  - Metal storage and transport proteins increase after exposure of the rat lung to
      an air pollution particle.
AB  - With the single exception of mercury, all metals in the atmosphere are associated
      with particles. The lungs are subsequently exposed to metals present in air
      pollution particles on a continuous basis. Because metal exposure can be
      associated with an oxidative stress, a mechanism that isolates the metal in a
      chemically less reactive form would be of benefit. We tested the hypothesis that
      the concentrations of both lactoferrin and ferritin in the rat lung increase
      after exposure to a metal-rich emission source air pollution particle. Using
      immunohistochemistry, we characterized changes in the concentrations of ferritin
      and lactoferrin after exposure of rats to an emission source air pollution
      particle. Lavage metal concentrations, measured by inductively coupled plasma
      emission spectroscopy, increased 4 hr after exposure to an oil fly ash. After
      exposure to this metal-rich emission source air pollution particle, ferritin
      concentrations in the lower respiratory tract increased. Comparable to the iron
      storage protein, concentrations of both lactoferrin and transferrin were elevated
      after exposure. The greatest concentrations of ferritin, lactoferrin, and
      transferrin occurred at approximately 24 hr after exposure to the air pollution
      particle. Levels then decreased, and by 96 hr after instillation of the oil fly
      ash, ferritin, lactoferrin, and transferrin were not elevated relative to those
      animals exposed to saline. We conclude that, in response to an emission source
      air pollution particle with high concentrations of metals, there is an increase
      in ferritin, lactoferrin, and transferrin concentrations in the lungs of the
      host. The function of these increases in iron-binding proteins may be to control
      the oxidative stress associated with the exposure to metals.

PMID- 9608646
TI  - Glycine modulates the toxicity of benzyl acetate in F344 rats.
AB  - The influence of supplemental glycine on benzyl acetate (BA; a compound
      metabolized via the hippurate pathway)-induced toxicity was investigated. Groups
      of male F344 rats were fed NIH-07 diet containing 0, 20,000, 35,000, or 50,000
      ppm BA for up to 28 days. Two additional groups were fed NIH-07 diet with 50,000
      ppm BA and 27,000 ppm glycine or 50,000 ppm BA 32,000 ppm L-alanine; supplemental
      glycine and L-alanine were equimolar. The L-alanine group served as an amino
      nitrogen control. A third group was fed NIH-07 diet with 32,000 ppm L-alanine and
      served as an untreated isonitrogenous control BA caused increase in mortality,
      body weight loss, the incidence of abnormal neurobehavioral signs such as ataxia
      and convulsions, along with astrocyte hypertrophy and neuronal necrosis in the
      cerebellum, hippocampus, and pyriform cortex of the brain. These effects were
      reduced significantly by supplementation with glycine but not with L-alanine.
      These results suggest that the neurodegeneration induced by BA is mediated by a
      depletion of the glycine pool and the subsequent excitotoxicity.

PMID- 9608647
TI  - Quantitation of glandular gastric changes in rats given a proton pump inhibitor
      for 3 months with emphasis on sampling scheme selection.
AB  - Proton pump inhibitors and H2-receptor antagonists suppress gastric acid
      secretion and secondarily induce hypergastrinemia. Sustained hypergastrinemia has
      a trophic effect on stomach fundic mucosa, including enterochromaffin-like (ECL)
      cell hypertrophy and hyperplasia. Histomorphometric quantitation of the
      pharmacologic gastric effects was conducted on 10 male and 10 female rats treated
      orally with LY307640 sodium, a proton pump inhibitor, at daily doses of 25, 60,
      130, or 300 mg/kg for 3 mo. Histologic sections of glandular stomach, stained for
      chromogranin A, were evaluated by image analysis to determine stomach mucosal
      thickness, mucosal and nonmucosal (submucosa and muscularis) area, gastric
      glandular area, ECL cell number/area and cross-sectional area. Total mucosal and
      nonmucosal tissue volumes per animal were derived from glandular stomach
      volumetric and area data. Daily oral doses of compound LY307640 sodium caused
      slight to moderate dose-related mucosal hypertrophy and ECL cell hypertrophy and
      hyperplasia in all treatment groups as compared with controls. All observed
      effects were prominent in both sexes but were generally greater in females. The
      morphometric sampling schemes were explored to optimize the data collection
      efficiency for future studies. A comparison between the sampling schemes used in
      this study and alternative schemes was conducted by estimating the probability of
      detecting a specific percentage of change between the male control and high-dose
      groups based on Tukey's trend test. The sampling scheme analysis indicated that
      mucosal thickness and mass had been oversampled. ECL cell density quantitation
      efficiency would have been increased by sampling the basal mucosa only for short
      term studies. The ECL cell size sampling scheme was deemed appropriate for this
      type of study.

PMID- 9608648
TI  - Immunohistochemical localization of microcystin-LR in the liver of mice: a study
      on the pathogenesis of microcystin-LR-induced hepatotoxicity.
AB  - The relationship between the intralobular sites of hepatotoxic injury and the
      distribution of microcystin-LR (MCLR), an inhibitor of protein phosphatases 1
      (PP1) and 2A (PP2A), was examined using an immunohistochemical method with a
      monoclonal antibody specific to MCLR on the livers of mice receiving a single
      i.p. injection of the MCLR. Immunoblotting and high-performance liquid
      chromatography analyses of liver extracts were also performed to determine the
      binding form of MCLR to PP1 and PP2A (MCLR-PP1/PP2A adducts) and free MCLR.
      Immunohistochemistry revealed a discernible intensity of staining in the
      centrilobular regions where hemorrhage and apoptosis occurred. In these regions,
      immunopositivity was evident in the cytoplasm and nuclei of the hepatocytes; some
      apoptotic cells were also immunopositive. In contrast, coagulative necrosis,
      which was mainly evident in the midlobular regions, was completely negative.
      Analysis of liver extracts demonstrated MCLR-PP1/PP2A adducts, but free MCLR was
      below detection limit. These results suggest that the immunohistochemical
      localization of MCLR in centrilobular hepatocytes is closely associated with the
      onset of hemorrhage and apoptosis and is related to adduct formation. The
      occurrence of coagulative necrosis however might also be related to other factors
      such as ischemia/hypoxia.

PMID- 9608649
TI  - Spontaneous proliferative lesions in the nasopharyngeal meatus of F344 rats.
AB  - Spontaneous proliferative lesions in the nasopharyngeal meatus were identified as
      the cause of death in 12 of 1,600 male and 5 of 1,600 female Fisher 344 (F344)
      rats used in 2-yr carcinogenicity studies; none of the lesions were considered
      treatment related. All the rats showed dyspnea, abdominal distension, and
      clinical deterioration. Gross features were characterized by simultaneous
      occurrence of conspicuous gaseous distension of the intestinal tract, especially
      in the ileum and cecum, and focal nodular lesions in the nasopharyngeal meatus.
      Histopathologically, the nasopharyngeal meatus was partially obstructed by the
      following proliferative lesions: 3 areas of hyperplasia of the ectopic sebaceous
      glands in the soft and hard palate, 4 areas of squamous metaplasia (SM) with
      massive hyperkeratosis, 5 squamous cell papillomas (SCPs), and 5 squamous cell
      carcinomas (SCCs). No pathological changes were found in the distended portion of
      the intestinal tract. Formalin-fixed, paraffin-embedded samples of the
      proliferative lesions from the nasopharyngeal meatus were examined for the
      presence of mutations in the c-H-ras and c-K-ras genes. In vitro amplification of
      DNA using a polymerase chain reaction was combined with a nonisotopic method for
      selective oligonucleotide hybridization. Two of the 4 SM lesions, 3 of the 5
      SCPs, and 5 of the 5 SCCs contained 1-3 point mutations in the c-H-ras and/or c-K
      ras gene. Immunohistochemically, overexpression of p53 protein was found in 1
      area of SM with a dysplastic lesion and 2 SCCs. These findings indicate that
      detailed examination of the upper respiratory system, including the
      nasopharyngeal meatus, may be particularly helpful for identifying primary occult
      lesions in F344 rats that show only gut distension at necropsy in long-term
      toxicity studies. In addition, mutations of the ras genes may be an important
      step in the early stages of carcinogenesis in the rat nasopharyngeal meatus,
      whereas p53 mutations could occur relatively late.

PMID- 9608650
TI  - Spontaneous neoplasm incidences in Fischer 344 rats and B6C3F1 mice in two-year
      carcinogenicity studies: a National Toxicology Program update.
AB  - Spontaneous neoplasm rates were determined for control Fischer 344 (F344) rats
      and B6C3F1 mice from 2-yr rodent carcinogenicity studies carried out by the
      National Toxicology Program (NTP). The most frequently occurring neoplasms in
      untreated male F344 rats were testicular adenoma (89.1%), mononuclear cell
      leukemia (50.5%), adrenal gland pheochromocytoma (31.9%), and pituitary gland
      neoplasms (30.4%). For untreated female F344 rats, the most frequently occurring
      neoplasms were pituitary gland neoplasms (54.2%), mammary gland fibroadenoma
      (41.2%), and mononuclear cell leukemia (28.1%). The most frequently occurring
      neoplasms in untreated male B6C3F1 mice were liver adenoma/carcinoma (42.2%),
      lung adenoma/carcinoma (20.5%), and malignant lymphoma (8.3%). For untreated
      female B6C3F1 mice, the most frequently occurring neoplasms were liver
      adenoma/carcinoma (23.6%), malignant lymphoma (20.9%), and pituitary gland
      adenoma/carcinoma (14.8%). The tumor rates observed in feeding study (untreated)
      and inhalation study (chamber) control rats were generally similar. The major
      exceptions were pituitary gland tumors and testicular adenoma in male F344 rats.
      The overall incidence of testicular adenoma was much lower in chamber controls
      (69.4%) than in feeding study controls (89.1%), whereas pituitary gland neoplasm
      showed the opposite trend (60.7% vs 30.4%). The most likely explanation for this
      difference is related to the individual housing of chamber controls and the group
      housing of feeding study controls. Differences in diagnostic criteria may
      influence reported tumor rates. To ensure consistency and comparability of tumor
      diagnosis from study to study, the NTP uses rigorous histopathology quality
      assurance and peer review procedures. Biological factors such as body weight may
      also affect tumor incidence. For example, increased body weights are associated
      with increased incidences of certain site-specific neoplasms, especially
      pituitary gland and mammary gland neoplasms in rats and liver tumors in mice. The
      presence of Helicobacter hepaticus has been associated with an increased
      incidence of liver neoplasms in male B6C3F1 mice. Other factors that may produce
      differences in control tumor rates from study to study include diet,
      environmental factors, genetic drift, study duration, and survival differences.
      The NTP database provides historical control data that may be useful in the
      evaluation of possible chemically related changes in tumor incidence. However, it
      is essential that the study being evaluated be comparable to those in the NTP
      database with respect to those factors that are known to influence tumor
      occurrence.

PMID- 9608651
TI  - Dermatotoxicity of agricultural chemicals in the dorsal skin of hairless dogs.
AB  - Dermatotoxicity of agricultural chemicals (ACs) with or without ultraviolet (UV)
      irradiation was histologically examined using hairless descendants of Mexican
      hairless dogs. ACs examined were pentachlorophenol sodium salt, 2,4
      dichlorophenoxyacetic acid (DCPAA), Maneb, and Zineb. One day after cessation of
      the 7-day AC treatment, the skin treated with DCPPA and Maneb indicated only
      slight histological changes. The UV + AC-treated sites had as much pigmentation
      as the control sites. Fourteen days after cessation of treatment, dogs treated
      with Maneb showed marked reactions such as epidermal degeneration, vasodilation,
      and intradermal infiltration of inflammatory cells. These histological changes
      were more severe in the UV + AC-treated sites. Zineb induced comedones with well
      developed pilosebaceous glands. These results suggest that hairless dogs may be
      useful laboratory animals for the investigation of dermatotoxicity of ACs in
      conjunction with UV irradiation.

PMID- 9608652
TI  - A spontaneous seminal vesicle adenocarcinoma in an aged F344 rat.
AB  - A rare seminal vesicle adenocarcinoma was found in a 109-wk-old Fischer 344
      (F344) rat. At necropsy, the right seminal vesicle was enlarged, containing a 15-
      x 18- x 18-mm mass. The neoplasm occupied almost the entire seminal vesicle lumen
      and consisted of epithelial cells arranged in papillary, glandular, and solid
      patterns. Tumor cells were larger than their normal counterparts in the seminal
      vesicles and had round nuclei and abundant cytoplasm. Clusters of macrophagelike
      cells with less abundant cytoplasm and indented nuclei were apparent in the
      lumina of the glandular structures formed by the tumor cells. No metastasis to
      other tissues or organs was observed. Immunohistochemically, tumor cells were
      positive for keratin and S-100, and the macrophagelike cells bound antibodies
      against vimentin and ED-1. Ultrastructurally, the tumor cells exhibited many
      small secretory granules, some microvilli, and intercellular junctions. The
      macrophagelike cells, in contrast, were characterized by lysosomes and abundant
      rough endoplasmic reticulum. Therefore, a diagnosis of seminal vesicle
      adenocarcinoma with intraluminal macrophage infiltration was made. This is the
      first case report of such a seminal vesicle tumor in an F344 rat.

PMID- 9608653
TI  - Phenotypic properties of preneoplastic rat liver lesions and applications to
      detection of carcinogens and tumor promoters.

PMID- 9608654
TI  - The carcinogenic risk of ethene (ethylene).

PMID- 9608655
TI  - "Have you seen this?" Bone marrow infarct in a cynomolgus monkey.

PMID- 9608656
TI  - Gag-Pol region determines the tropism of SIVagm for human cells.
AB  - Simian immunodeficiency virus isolated from African green monkeys (SIVagm) does
      not grow in many of human cell lines such as CEM x 174, H9, and MT-4, but could
      replicate in some human cell lines. Sequence of SIVagm responsible for its narrow
      host range was determined by making and monitoring growth potential of chimeric
      clones between SIVagm and human immunodeficiency virus type 1 (HIV-1). The
      results obtained indicated that the gag-pol region determines the observed narrow
      host range. By monitoring virus DNA synthesis and progeny virion production, the
      defect(s) of SIVagm in the replication in the restricted cells was demonstrated
      to be located at early phase.

PMID- 9608657
TI  - The characterization of a subgenomic RNA and in vitro translation products of oat
      chlorotic stunt virus.
AB  - Oat chlorotic stunt virus (OCSV) is a 35 nm icosahedral plant virus comprising of
      a single capsid protein with a Mr of 48.2 kDa and a 4.1 kb single stranded,
      positive sense genomic RNA. Northern blot analysis detected a single 3' terminal
      subgenomic RNA in extracts from infected plants, which was also found to be
      encapsidated. Virion RNA directs the synthesis of a 23 kDa polypeptide in a
      rabbit reticulocyte in vitro translation system. Primer extension analysis has
      been used to map the end of both the genomic and subgenomic RNA's, and has shown
      the genomic size to be 4115 nucleotides in length. The results have enabled a
      model for the genome expression to be proposed.

PMID- 9608658
TI  - Does the latency associated transcript (LAT) of herpes simplex virus (HSV)
      function as a ribozyme during viral reactivation?
AB  - The latency associated transcript (LAT) of herpes simplex virus (HSV) appears to
      exist as an RNA molecule only. This phenomenon is consistent with the concept of
      functioning at an RNA level, and several lines of evidence suggest that the LAT
      may be a ribozyme. This provides an insight into understanding the role of LAT
      during HSV reactivation.

PMID- 9608659
TI  - A single amino-acid substitution in gag p19 protein (MA) of Rous sarcoma virus
      suppresses virus production from infected cells.
AB  - Gag p19 protein (MA) of the transformation-defective Rous sarcoma virus mutant,
      tdPH2010, has a point mutation at nucleotide 376 (G to A) that results in an
      amino-acid change at residue 126 of p19 (Glu to Lys). This single amino-acid
      change is the cause of the aberrantly fast migration of this protein on SDS
      polyacrylamide gels. To study the biological significance of the mutation, we
      introduced this mutation into a transformation-defective derivative of the
      molecularly cloned Rous sarcoma virus, SRA2, and examined its effect on virus
      replication. The virus possessing the mutation in its gag p19 gene had 50% slower
      replication as measured by the amount of reverse transcriptase as well as gag p27
      protein (CA) in the culture media. Glu at position 126 appears to be important
      for efficient production of Rous sarcoma virus in vitro.

PMID- 9608660
TI  - Effects of mutations within the SV40 large T antigen ATPase/p53 binding domain on
      viral replication and transformation.
AB  - The simian virus 40 (SV40) large T antigen is a 708 amino-acid protein possessing
      multiple biochemical activities that play distinct roles in productive infection
      or virus-induced cell transformation. The carboxy-terminal portion of T antigen
      includes a domain that carries the nucleotide binding and ATPase activities of
      the protein, as well as sequences required for T antigen to associate with the
      cellular tumor suppressor p53. Consequently this domain functions both in viral
      DNA replication and cellular transformation. We have generated a collection of
      SV40 mutants with amino-acid deletions, insertions or substitutions in specific
      domains of the protein. Here we report the properties of nine mutants with single
      or multiple substitutions between amino acids 402 and 430, a region thought to be
      important for both the p53 binding and ATPase functions. The mutants were
      examined for the ability to produce infectious progeny virions, replicate viral
      DNA in vivo, perform in trans complementation tests, and transform established
      cell lines. Two of the mutants exhibited a wild-type phenotype in all these
      tests. The remaining seven mutants were defective for plaque formation and viral
      DNA replication, but in each case these defects could be complemented by a wild
      type T antigen supplied in trans. One of these replication-defective mutants
      efficiently transformed the REF52 and C3H10T1/2 cell lines as assessed by the
      dense-focus assay. The remaining six mutants were defective for transforming
      REF52 cells and transformed the C3H10T1/2 line with a reduced efficiency. The
      ability of mutant T antigen to transform REF52 cells correlated with their
      ability to induce increased levels of p53.

PMID- 9608662
TI  - Complete nucleotide sequence of the genomic RNA of tobacco mosaic virus strain
      Cg.
AB  - Tobacco mosaic virus (TMV)-Cg is a crucifer-infecting tobamovirus that was
      isolated from field-grown garlic. We determined the complete nucleotide sequence
      of the genomic RNA of TMV-Cg. The genomic RNA of TMV-Cg consists of 6303
      nucleotides and encodes four large open reading frames, organized basically in
      the same way as that of other tobamoviruses. The nucleotide and deduced amino
      acid sequences are very similar to those of the other crucifer-infecting
      tobamoviruses that have been sequenced so far.

PMID- 9608661
TI  - The foot and mouth disease virus type O outbreak of 1992 is not related to
      vaccine strain (O/R2/75).
AB  - Vaccination is the only pragmatic approach to control foot and mouth disease in
      India. Strict quality control measures are essential to supply potent vaccine to
      the field application, in addition to monitoring the performance of the vaccine
      in the field. During the process of monitoring, an outbreak of FMD in vaccinated
      animals caused by type "O" virus in Tanjavur district of Tamil Nadu and a type
      "O" virus from unvaccinated herd of Karnataka were studied. Field isolates and
      vaccine virus were sequenced and analyzed. Data indicated that the virus from the
      outbreak in vaccinated cattle was a variant which could escape neutralization by
      antibodies against vaccine virus.

PMID- 9608663
TI  - The rubella virus putative replicase interacts with the retinoblastoma tumor
      suppressor protein.
AB  - In utero fetal infection of rubella virus (RV), a positive-stranded RNA virus,
      frequently induces birth defects if contracted in the first trimester of
      pregnancy. The underlying mechanism of RV-induced birth defects is not known.
      Birth defects are also common in certain DNA viral infections such as human
      cytomegalovirus (HCMV). During HCMV infection, one of its proteins interacts with
      a cell growth regulatory protein, the retinoblastoma protein (Rb) and stimulates
      DNA synthesis which is associated with chromosomal damage and cellular mitotic
      arrest. These affects have been implicated in HCMV induced teratogenesis. Since
      RV and HCMV both cause teratogenesis, we postulated that during RV infection, a
      virus-encoded protein might interact with Rb and affect fetal cell growth. In the
      present study, we have identified a known Rb-binding motif, L x C x E (LPCAE) in
      the carboxy-terminal half of the putative replicase (NSP90) of RV and
      demonstrated that the C-terminal region specifically binds to GST-Rb in vitro.
      Further, by coimmunoprecipitating NSP90 and Rb using specific antibodies to
      respective proteins, we have confirmed that NSP90 specifically binds to Rb in
      vivo as well. In addition, RV replication was shown to be less in null-mutant (Rb
      /-) mouse embryonic fibroblast cells than in wild-type (Rb+/+) cells, suggesting
      a possible physiological role for this interaction. Thus, in facilitating RV
      replication, binding of NSP90 to Rb potentially alters the cell growth regulatory
      property of Rb, and this could be one of the initial steps in RV-induced
      teratogenesis.

PMID- 9608664
TI  - VP1-coding sequences of recent isolates of foot-and-mouth disease virus types A,
      O and Asia1.
AB  - A large part of the capsid protein VP1-coding sequence of foot-and-mouth disease
      virus, isolated between 1993 and 1996 in Europe, was amplified by the reverse
      transcription-dependent polymerase chain reaction (RT-PCR). The same was done
      with some non-European virus isolates, especially those against which vaccines
      were currently produced. The products were sequenced, and the sequences aligned.
      The alignment comprises sequences of the types A, O and Asia 1. Although the
      provenance of virus introduced to Europe remains unknown, genetic relation to
      some other isolates was indicated. Several genotypes of the virus were found to
      circulate in the field since years.

PMID- 9608665
TI  - HTLV-I associated sicca syndrome in Guadeloupe: lack of relation with a peculiar
      encoding sequence of surface envelope glycoprotein.
AB  - We previously reported a strikingly high prevalence of ocular diseases in HTLV-I
      infected patients in Guadeloupe (Caribbean basin). We sequenced the surface
      envelope encoding region of 7 HTLV-I proviruses from guadeloupean patients (5
      with sicca syndrome, 2 with TSP/HAM). No relation between sequence and disease
      was observed. These 7 sequences are the first described from Guadeloupe.

PMID- 9608666
TI  - Genome organization of Xestia c-nigrum granulovirus.
AB  - In order to characterize the genome organization of Xestia c-nigrum granulovirus
      (XcGV), mapping of putative XcGV genes was performed by construction of lambda
      and M13 phage libraries followed by Southern blot and nucleotide sequencing
      analyses. Mapping of the lambda (32 clones covering the entire XcGV genome) and
      M13 (133 clones made by random cloning) phage library clones was carried out by
      hybridization of the labeled lambda phage clone DNAs to 1) Southern blotted XcGV
      genomic DNA fragments cleaved with EcoRI, BamHI, or HindIII, and 2) dot blotted
      M13 clone DNAs. All 133 M13 clone DNAs were sequenced, and coding possibilities
      were investigated by computer-assisted homology search; in total, about 43 kb of
      the genome was sequenced. Amino acid sequence homology searches of 67 M13 clones
      suggested that these GV DNAs coded for previously characterized genes identified
      in nucleopolyhedroviruses (NPVs) and GVs. These 67 M13 clones were classified
      into 25 gene homolog groups (including 29 putative genes) based on their
      homologies to NPV and GV genes. The remaining M13 clones, except one that encoded
      a putative metalloproteinase, did not possess deduced amino acid sequences with
      significant homology to proteins in gene databases. Complete nucleotide sequences
      of the putative XcGV DNA polymerase and Ac144 homolog genes confirmed the
      reliability of our speculation of putative genes based on the M13 clones
      sequencing analysis. In a comparison of relative locations of putative XcGV genes
      with locations of their homologs in NPVs, most XcGV genes were mapped close to
      the corresponding locations in NPV genomes. These results suggested that XcGV,
      compared to NPVs, had relatively conserved gene arrangements, although about 22
      kb of 43 kb of DNA sequenced randomly in the XcGV genome consisted of
      sequences/genes non-homologous to those of previously characterized NPVs.

PMID- 9608667
TI  - Development of RT-PCR for turkey meningoencephalitis virus and partial sequence
      analysis of the NS5 gene.
AB  - Turkey meningoencephalitis virus (TMEV) causes paralysis and mortality in
      turkeys. Because the classical diagnostic methods are complicated, we developed
      the RT-PCR as a new molecular diagnostic method. Since the nucleic acid sequence
      of TMEV is unknown, the first step in developing the RT-PCR relied on conserved
      sequences of viruses belonging to the Flaviviridae family, in which TMEV has been
      classified serologically. Using primers from the NS5 gene, three amplification
      products of TMEV RNA were obtained (125 bp, 181 bp and 800 bp). Their sequences
      were homologous to one another and to the NS5 gene of other flaviviruses.

PMID- 9608668
TI  - Cloning, expression and sequence analysis of the classical swine fever virus
      nucleocapsid protein.
AB  - The DNA complementary to the 5'-terminal 1929 nucleotides of classical swine
      fever virus (CSFV; alias hog cholera virus, HCV) LPC vaccine strain RNA was
      cloned and sequenced. The sequence encompasses a 5'-noncoding region (NCR) of 264
      nucleotides and an open reading frame (ORF) of 1665 nucleotides. The cloned
      sequence contains genes of four viral proteins, P23, nucleocapsid (core) protein,
      E0 and part of E1 proteins. Alignment of the 5'-terminal 1929 nucleotides of LPC
      strain with other strains of CSFV showed well conservation and a homology as high
      as 84-95% was found between these strains. The cDNA of CSFV-LPC core was cloned
      into an expression vector, and a fusion protein of 38.5 kDa was obtained which
      reacted strongly to CSFV antiserum. Purification of the core fusion protein was
      achieved by a single-step affinity chromatography and the purified product could
      be recognized by the sera of CSFV-infected swine in ELISA assay. Phylogenetic
      analysis of the 5'-terminal 1929 nucleotides between pestiviruses revealed that
      the 5'-end region seems to be suitable for differentiation of different strains
      of CSFV.

PMID- 9608669
TI  - The aquaporins. A family of water channel proteins.
AB  - The recent discovery of aquaporins, a family of highly conserved water channel
      proteins, which are expressed in both eukaryotes and prokaryotes, has provoked a
      re-evaluation of the physiology of water transport in all organisms. So far,
      seven distinct aquaporins have been characterised in mammals, but highly
      homologous family members have also been found in amphibians, insects, plants and
      bacteria. These transmembrane proteins serve to facilitate water transport down
      osmotic gradients with low activation energy. Alterations in channel expression,
      cellular targeting and perhaps channel permeability regulate membrane water
      transport. Naturally occurring and experimentally produced mutations in
      aquaporins cause a variety of perturbations of water homeostasis. Manipulation of
      aquaporin expression may have a therapeutic role in several disease processes
      including cardiac failure and the ascites associated with liver disease.

PMID- 9608670
TI  - Leukotriene B4.
AB  - Leukotriene B4 is a pro-inflammatory mediator synthesised in myeloid cells from
      arachidonic acid. Synthesis is catalysed by 5-lipoxygenase and leukotriene A4
      hydrolase and is increased by inflammatory mediators including endotoxin,
      complement fragments, tumor necrosis factor and interleukins. A nuclear membrane
      protein, 5-lipoxygenase activating protein, is an essential co-factor for 5
      lipoxygenase. Leukotriene B4 induces recruitment and activation of neutrophils,
      monocytes and eosinophils. It also stimulates the production of a number of
      proinflammatory cytokines and mediators indicating an ability to augment and
      prolong tissue inflammation. Elevated levels of leukotriene B4 have been found in
      a number of inflammatory diseases and levels are related to disease activity in
      some of these. Initial data from pharmacological inhibition studies support a
      role for leukotriene B4 in the pathogenesis of neutrophil mediated tissue damage,
      and treatments which reduce its production or block its effects may prove
      beneficial in neutrophil mediated inflammatory diseases.

PMID- 9608671
TI  - The integrin beta subunit.
AB  - The integrin family of cell adhesion receptors plays a fundamental role in the
      processes involved in cell division, differentiation and movement. The
      extracellular domains of integrin alpha/beta heterodimers mediate cell-matrix and
      cell-cell contacts while their cytoplasmic tails associate with the cytoskeleton.
      Integrins are capable of transducing information in a bidirectional manner and
      the beta subunit is now recognised to play an important role in this process.
      Recent studies have led to the identification of a ligand-binding region on the
      beta subunit similar to that already characterised on some alpha subunits, and
      sequences in the cytoplasmic tails of the beta subunits that interact with
      cytoskeletal and signalling components. Adhesive events can also play a role in
      the progression of all four major classes of human disease--neoplastic,
      inflammatory, traumatic and infectious--and the specific nature of integrin
      adhesion mechanisms make them an attractive target for therapy.

PMID- 9608672
TI  - Purification and isotype analysis of protein kinase C from rat liver nuclei.
AB  - The properties and subtype composition of protein kinase C present in rat liver
      nuclei were studied in a Triton-X-100 extract of isolated purified nuclei. The
      enzyme activity was dependent on both Ca2+ and phosphatidylserine, but the
      phorbol ester 12-O-tetradecanoylphorbol 13-acetate gave only a partial
      stimulation. Both histone and myelin basic protein served as substrate.
      Purification of the Triton-X-100 extract followed by Q-Sepharose chromatography
      gave a preparation with a specific activity of 70 pmol/mg protein min. Western
      blotting of this preparation showed only the presence of the delta and zeta
      subtypes, but not the alpha-subtype, although the latter was present in rat liver
      homogenates. The beta, gamma and epsilon subtypes were not found in the
      homogenate nor in the nuclear extract. The specific activity of protein kinase C
      could be further increased up to 800 pmol/mg protein min after protamine agarose
      chromatography. Also in this preparation the presence of the delta and zeta
      subtypes could be established.

PMID- 9608673
TI  - Abnormal content of n-6 and n-3 long-chain unsaturated fatty acids in the
      phosphoglycerides and cholesterol esters of parahippocampal cortex from
      Alzheimer's disease patients and its relationship to acetyl CoA content.
AB  - The long-chain fatty acid composition of cholesterol esters, phosphatidylcholine
      (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS) and
      phosphatidylinositol (PI) from parahippocampal cortex of Alzheimer's disease (AD)
      patients and control subjects was examined. In general the PC fraction contained
      less polyunsaturated long-chain fatty acids than did PE, PS or PI. Of the n-6
      polyunsaturated long-chain fatty acids, PI contained the greatest incorporation
      of these acids followed by PE. There were significant differences between
      controls and AD patients in total n-6 EFAs. Arachidonic acid (C20:4n-6) was the
      predominant fatty acid of this family found to be present. In AD, PE and PS
      showed a deficit of adrenic acid (C22:4n-6) content and PE also contained less
      arachidonic acid. In AD subjects, the cholesterol esters contained significantly
      less n-3 polyunsaturated fatty acids with, specifically, a reduction in alpha
      linolenic acid. Acetyl CoA content of hippocampal cortex was greater in AD
      patients than in control subjects indicating either an increased extent of
      oxidative metabolism or a failure to utilise acetyl CoA for anabolic processes.
      Abnormal magnitude of oxidative processes could give rise to the biosynthesis of
      PE and PS species containing less n-6 polyunsaturated fatty acids than occurs in
      control subjects.

PMID- 9608674
TI  - The decrease of liver LDL receptor mRNA during fasting is related to the decrease
      in serum T3.
AB  - Fasting is associated with a reduction in serum T3 and T4 and a rise of plasma
      LDL cholesterol. We hypothesized that an hypothyroid-like condition induced by
      fasting is responsible for the rise in LDL cholesterol. We therefore examined the
      relation between changes in thyroid hormone and cholesterol metabolism in rats
      fasted for 0, 8, 12, 24 or 48 h. Fasting resulted in a decrease of liver 5'
      deiodinase mRNA from 8 h (to 50%, p < 0.05, n = 6), of serum T3 from 12 h and of
      serum T4 at 48 h; serum TSH remained unchanged. Furthermore, plasma LDL
      cholesterol increased from 24 h onwards preceded by a decrease of liver LDL
      receptor mRNA which in turn is related to serum T3 (r = 0.55, p < 0.05, n = 19).
      Adding T3 at a concentration such that normal T3 levels are maintained during 48
      h fasting, prevents the decrease in the LDL receptor mRNA. Fasting did not change
      hepatic HMG CoA reductase mRNA but decreased cholesterol 7 alpha-hydroxylase
      mRNA, which however was not related to the decrease of serum T3. IN CONCLUSION:
      (1) Fasting induces a hypothyroid-like condition in which inhibition of hepatic
      conversion of T4 into T3 may be responsible for the decrease of serum T3. (2)
      Fasting induces an increase of plasma LDL cholesterol, apparently caused by a
      decrease of hepatic LDL receptor gene expression which is (partly) related to the
      fall in serum T3.

PMID- 9608675
TI  - Identification of an endonuclease secreted by human B lymphoblastic IM9 cells.
AB  - We have identified a Mg(2+)-dependent endonuclease from IM9 cell lysates and
      culture medium using DNA-native-polyacrylamide gel electrophoresis (DNA-native
      PAGE) nuclease assay system. This particular endonuclease activity was not
      detectable in conventional DNA-SDS-polyacrylamide gel electrophoresis assay
      system which is similar to the method originally described by Rosenthal and Lacks
      (A.L. Rosenthal and S.A. Lacks, Anal. Biochem. 80 (1977) 76-90). Experimental
      results clearly demonstrated that the endonuclease activity was not derived from
      the fetal calf serum in which the cells were grown, but synthesized in the cell
      and secreted into the culture medium by IM9 cells. Biosynthesis and subsequent
      release of the endonuclease into the culture medium were significantly decreased
      by pretreatment of the cells with actinomycin D. Using supercoiled plasmid DNA as
      a substrate, the endonuclease activity was determined with the enzyme isolated
      from the cell culture medium by native-PAGE electroelution. The endonuclease,
      with Mg2+ alone, was able to catalyze the conversion of the plasmid into linear
      DNA followed by further degradation. This is the first report demonstrating that
      a distinct Mg(2+)-dependent endonuclease is secreted by a human immune cell line.

PMID- 9608676
TI  - Elucidation of a new biological function of an old protein: unique structure of
      the cobra serum albumin controls its specific toxin binding activity.
AB  - Although few proteins have been studies as thoroughly as serum albumin, a new
      biological property of this evolutionary ancient protein was recently discovered:
      The ability of cobra serum albumin (CSA) to specifically sequester lethal
      endogenous toxins. A study of the structural basis of this property is reported
      in this contribution. Two independent approaches were used to alter the structure
      of the CSA at defined positions: Directed mutagenesis and limited proteolysis.
      The conserved pattern of the disulfide linkages in the primary structure of the
      serum albumins showed in the case of the cobra snake (Naja naja kaouthia) an
      anomaly at C11 and C502, which suggested the existence of a unique spatial
      structure in this protein. The two cysteine residues were singly replaced with
      the consensus residue, i.e. C11-->F and C502-->T. The former substitution
      increased the specific neurotoxin binding capacity of the CSA by the factor 1.7
      +/- 0.2, whereas the latter replacement reduced it to (25 +/- 2)%. The limited
      proteolysis yielded the large tryptic peptides T60, T40, T30 and T18, which after
      isolation by PAGE followed by HPLC had retained a strong toxin affinity. The
      location of these peptides in the amino-acid sequence was identified by Edman
      degradation and suggested the order of their release. On the basis of these data,
      a model of the unfolding and of the activity changes of the CSA caused by the
      structural perturbations was composed and the kinetic parameters associated with
      the process were evaluated. The results support the hypothesis of the existence
      of a structure of multiple homologous domains with a disulfide linkage between
      C11 and C502 in the native CSA that joins the chain ends to form a dense
      conformation.

PMID- 9608677
TI  - Nocturnal increases in the triiodothyronine/thyroxine ratio in the rat thymus and
      pineal gland follow increases of type II 5'-deiodinase activity.
AB  - The type II 5'-deiodinase (5'D-II) is regulated by the light-dark cycle in some
      tissues in which the enzyme is present. This prompted us to investigate putative
      influences of light-dark cycle on thyroid hormone concentrations in these
      tissues. The results revealed the following facts: (a) Deiodinase activity in the
      rat thymus exhibits a nyctohemeral profile with peak values late at night and
      basal values during the day. The thyroid hormone concentrations in the thymus
      also show a 24 h rhythm with an increase in the triiodothyronine/thyroxine
      (TT3/TT4) ratio at night. (b) The content of thyroid hormones in the pineal gland
      exhibits, like in the thymus, nyctohemeral variations with increase values in the
      TT3/TT4 ratio during the dark period coinciding with the maximal enzyme activity.
      (c) Other tissue, like the anterior pituitary, in which 5'D-II, activity does not
      exhibit a diurnal variation, the concentration of thyroid hormones does not show
      modifications. In conclusion, the nocturnal increase of 5'D-II activity produces
      an increase of T3 concentration and a decrease of T4 concentration in both thymus
      and pineal gland. Therefore, these diurnal changes in 5'D-II activity is a mean
      by which the cell can regulate the intracellular availability of the most active
      thyroid hormone T3.

PMID- 9608678
TI  - L-3,4-dihydroxyphenylalanine and L-5-hydroxytryptophan share the same transporter
      in Opossum kidney cells.
AB  - Opossum kidney (OK) cells, which have the ability to synthesise dopamine and 5
      HT, have been used as an in vitro model for the study of renal actions of
      dopamine and 5-hydroxytryptamine (5-HT). The present study reports on the uptake
      of their immediate precursors L-3,4-dihydroxyphenylalanine (L-DOPA) and L-5
      hydroxytryptophan (L-5-HTP). IC50 values for L-5-HTP (1569 microM) obtained in
      the presence of a nearly saturating (250 microM) concentration of L-DOPA were 6
      fold those obtained when using non-saturating (0.25 and 25 microM) concentrations
      of L-DOPA (251 and 266). Vmax values (in nmol mg protein-1 6 min-1) for L-DOPA
      uptake are identical in the absence (13.6) and the presence of 250 microM L-5-HTP
      (13.3), but K(m) values (microM) are significantly greater (P < 0.05) when L-DOPA
      uptake was studied in the presence of L-5-HTP (90 vs 1.79). IC50 values for L
      DOPA (679 microM) obtained in the presence of a near saturating (250 microM)
      concentration of L-5-HTP were almost 3-fold those obtained when non-saturating
      (0.25 and 25 microM) concentrations of L-5-HTP were used (254 and 220). Vmax
      values (in nmol mg protein-1 6 min-1) for L-5-HTP uptake are identical in the
      absence (11.2) and the presence of 250 microM L-DOPA (11.7), but K(m) values
      (microM) are significantly greater (P < 0.05) when L-5-HTP uptake was studied in
      the presence of L-DOPA (103 vs 220). It is concluded that L-DOPA and L-5-HTP
      share the same transporter(s) and each compound exerts a competitive type of
      inhibition upon the other.

PMID- 9608679
TI  - Lipid-protein complexes as cholesterol pronucleating agents in human bile.
AB  - Among the various substances which accelerate the formation of cholesterol
      crystals in cholesterol supersaturated bile are proteins obtained from the bile
      by affinity chromatography on con A-Sepharose. Several such con A binding
      proteins have been identified and shown to mediate acceleration of cholesterol
      crystal formation in vitro. However, the major protein fraction, which does not
      bind con A, has been studied rarely. Investigation of the effect of this latter
      bile protein fraction on cholesterol crystallization is the aim of this study.
      Contrary to results published to date, the con A nonbinding protein fraction
      exerted a higher cholesterol crystallization promoting activity than the con A
      binding fraction. Delipidation as well as proteolytic degradation sharply
      decreased the activity of both fractions. Albumin was identified as the main
      component of the con A nonbinding fraction. A lipid-protein complex formed from
      the lipid and albumin possessed a very high cholesterol crystallization promoting
      activity whereas albumin or the lipid alone showed much lower activity. Bivalent
      ions, especially Mn2+ and Ca2+, increased the promoting activity of the lipid
      protein complex. Thus, albumin and other bile protein can bind noncovalently
      biliary lipid material and such lipid-protein complexes may act as the main
      cholesterol crystallization promoter in the human bile.

PMID- 9608680
TI  - Pax7 includes two polymorphic homeoboxes which contain rearrangements associated
      with differences in the ability to regenerate damaged skeletal muscle in adult
      mice.
AB  - Pax7 is a paired-type homeobox gene which has previously been shown to play an
      important role in skeletal muscle formation. It is expressed in skeletal muscle
      of the limbs during embryogenesis and in adulthood. The aims of this study were
      firstly to determine the degree of polymorphism of Pax7 amongst inbred laboratory
      mice using Southern blotting and Pax7 regional specific sub-probes. Secondly,
      functional studies were performed on mice with each of the different structural
      forms of Pax7 to determine whether they were associated with differences in the
      ability to regenerate damaged skeletal muscle. Four different allelic forms of
      Pax7 have now been identified in laboratory mice indicating that the previously
      reported DNA sequence of Pax7 is not applicable to all laboratory mice.
      Hybridisation patterns of TaqI digested DNA representing each of the different
      Pax7 alleles with the Pax7 specific sub-probes suggested that in contrast to
      previous findings, Pax7 is associated with two highly polymorphic homeoboxes. The
      presence of two homeoboxes in BALB/c mice has been confirmed by DNA sequencing.
      Results of functional studies have also shown that the ability to regenerate
      damaged skeletal muscle in adult mice is strongly associated with the presence of
      a 0.15-kb TaqI fragment derived from one of the homeoboxes.

PMID- 9608681
TI  - Effects of wortmannin and rapamycin on CSF-1-mediated responses in macrophages.
AB  - There are differing views regarding the roles of phosphatidylinositol 3-kinases
      (PI3-kinases) and p70 S6 kinase (p70s6k) in growth factor-induced cellular
      responses. One approach that is widely employed to investigate these roles is to
      use the inhibitors, wortmannin and rapamycin, respectively. This approach is used
      here to study the responses in macrophages to colony stimulating factor-1 (CSF
      1). Wortmannin (> or = 30 nM) and rapamycin (> or = 3 nM) both weakly inhibited
      CSF-1-stimulated DNA synthesis in murine bone marrow-derived macrophages (BMM),
      suggesting that there are PI3-kinase- and p70s6k-independent pathways required
      for the onset of S phase; interestingly the combination of the drugs gave
      dramatic suppression. Inhibition of DNA synthesis by rapamycin on the BMM was
      much less than that observed with the CSF-1-dependent cell line, BAC1.2F5. In
      BMM, wortmannin suppressed CSF-1-stimulated increase in p70s6k activity
      indicating that PI3-kinase activity may lie upstream. In contrast to some other
      growth factor/cell systems, no evidence was obtained using the inhibitors for the
      involvement of PI3-kinase or p70s6k in CSF-1-mediated induction of c-fos mRNA
      expression or Erk-1 activity; in addition, no evidence was found for an
      involvement in the CSF-1-mediated increase in cyclin D1 expression or STAT
      activation. The findings reinforce the need to study the signal transduction
      cascades relevant to each individual growth factor and preferably not in cell
      lines.

PMID- 9608682
TI  - Heme oxygenase induction by UVA radiation. A response to oxidative stress in rat
      liver.
AB  - Heme oxygenase is a key enzyme for heme catabolism and catalyzes the oxidative
      degradation of heme to form biliverdin IX alpha, an immediate precursor of
      bilirubin. In order to shed light on the mechanism by which UVA radiation causes
      oxidative damage, the relationship between heme oxygenase induction and oxidative
      stress was studied. HO-1 activity, lipid peroxidation and generation of active
      oxygen species (H2O2) were measured in rat liver exposed to UVA radiation.
      Besides, soluble and enzymatic antioxidant defenses (GSH, SOD, CAT and GSH-Px)
      were determined, while bilirubin antioxidant capacity was also evaluated. UVA
      radiation markedly increased both lipid peroxidation (180% +/- 7; S.E.M., n = 9
      over control value of 0.1 +/- 0.01 nmol MDA/min per mg prot.) and steady state
      concentration of hydrogen peroxide (4 +/- 0.03 microM; S.E.M., n = 9) 3 h after
      treatment. At the same time, GSH content decreased to 3.6 +/- 0.2 mumol/g liver
      (S.E.M., n = 9) increasing thereafter. Antioxidant enzymes reached minimum values
      6 h after UVA treatment (SOD: 7.2 +/- 0.2 U/mg protein, CAT: 7.8 +/- 0.2 pmol/mg
      protein, GSH-Px: 0.088 +/- 0.004 U/mg protein; S.E.M., n = 9), starting to
      increase 12 h after irradiation. HO-1 induction was observed 6 h after UVA
      irradiation, reaching a maximum value of 2.5 +/- 0.03 U/mg protein (S.E.M., n =
      9) 12 h after treatment, and then declined until it reached control levels 24 h
      after exposure. Administration of bilirubin 2 h before UVA irradiation, entirely
      prevented HO-1 induction, the increase in MDA content and the decrease in GSH
      levels. This study shows that UVA irradiation leads to oxidative stress as
      evidenced by increased MDA content and H2O2 steady state levels, and depletion of
      GSH, SOD, CAT and GSH-Px. All these changes produced HO-1 induction. It is
      concluded that the induction of this enzyme could be a response to oxidative
      stress, since bilirubin can act as a physiological antioxidant.

PMID- 9608683
TI  - Mitochondrial DNA sequencing of shed hairs and saliva on robbery caps:
      sensitivity and matching probabilities.
AB  - Sequencing of mitochondrial DNA (mtDNA) has been used for human identification
      based on teeth and skeletal remains. Here, we describe an amplification system
      for the mtDNA control region (D-loop) suited for the analysis of shed hair, which
      constitutes the most common biological evidence material in forensic
      investigations. The success rate was over 90% when applied to evidence materials
      such as shed hair, saliva stains and saliva on stamps. The analysis of evidence
      materials collected from three similar robberies revealed the presence of mtDNA
      sequences identical to those of the suspects in the three crimes. The use of
      mtDNA control region sequences for individual identification was evaluated. The
      probability of identity by chance for the mtDNA types of the suspects in the
      robberies was found to vary between Pr = 0.017 - < 0.0017, depending on the
      reference population used, emphasizing the need for large population databases to
      obtain the appropriate estimate.

PMID- 9608684
TI  - Interlaboratory comparison of autoradiographic DNA profiling measurements:
      precision and concordance.
AB  - Knowledge of the expected uncertainty in restriction fragment length polymorphism
      (RFLP) measurements is required for confident exchange of such data among
      different laboratories. The total measurement uncertainty among all Technical
      Working Group for DNA Analysis Methods laboratories has previously been
      characterized and found to be acceptably small. Casework cell line control
      measurements provided by six Royal Canadian Mounted Police (RCMP) and 30 U.S.
      commercial, local, state, and Federal forensic laboratories enable quantitative
      determination of the within-laboratory precision and among-laboratory concordance
      components of measurement uncertainty typical of both sets of laboratories.
      Measurement precision is the same in the two countries for DNA fragments of size
      1000 base pairs (bp) to 10,000 bp. However, the measurement concordance among the
      RCMP laboratories is clearly superior to that within the U.S. forensic community.
      This result is attributable to the use of a single analytical protocol in all
      RCMP laboratories. Concordance among U.S. laboratories cannot be improved through
      simple mathematical adjustments. Community-wide efforts focused on improved
      concordance may be the most efficient mechanism for further reduction of among
      laboratory RFLP measurement uncertainty, should the resources required to fully
      evaluate potential cross-jurisdictional matches become burdensome as the number
      of RFLP profiles on record increases.

PMID- 9608685
TI  - Using a tree diagram to interpret a mixed DNA profile.
AB  - A recent case is described where the evidence of bloodstaining on a knife
      suggested that it was a mixture from the two victims. Interpretation of the
      evidence in this problem necessitated the formulation of several sets of multiple
      hypotheses which were analyzed by means of a tree diagram. The problem was then
      greatly simplified to one of comparing the two alternative hypotheses of most
      interest. It was found that results were robust to variation in the expert's
      judgment regarding the possibility that a mixture of blood was present on the
      knife.

PMID- 9608687
TI  - Effect of reference database on frequency estimates of polymerase chain reaction
      (PCR)-based DNA profiles.
AB  - A variety of general, regional, ancestral and ethnic databases is available for
      the polymerase chain reaction (PCR)-based loci LDLR, GYPA, HBGG, D7S8, Gc, DQA1,
      and D1S80. Generally, we observed greater differences in frequency estimations of
      DNA profiles between racial groups than between ethnic or geographic subgroups.
      Analysis revealed few forensically significant differences within ethnic
      subgroups, particularly within general United States groups, and multi-locus
      frequency estimates typically differ by less than a factor of ten. Using a
      database different from the one to which a target profile belongs tends to
      overestimate rarity. Implementation of the general correction of homozygote
      frequencies for a population substructure, advised by the 1996 National Research
      Council report, The Evaluation of Forensic DNA Evidence, has a minimal effect on
      profile frequencies. Even when it is known that both the suspect and all possible
      perpetrators must belong to the same isolated population, the special correction
      for inbreeding, which was proposed by the 1996 National Research Council report
      for this special case, has a relatively modest effect, typically a factor of two
      or less for 1% inbreeding. The effect becomes more substantial (exceeding a
      factor of ten) for inbreeding of 3% or more in multi-locus profiles rarer than
      about one in a million.

PMID- 9608686
TI  - Sex identification of elk (Cervus elaphus canadensis), moose (Alces alces), and
      white-tailed deer (Odocoileus virginianus) using the polymerase chain reaction.
AB  - We have developed a PCR-based protocol to determine the gender of tissue samples
      originating from elk (Cervus elaphus canadensis), moose (Alces alces) and white
      tailed deer (Odocoileus virginianus). The technique simultaneously amplifies a
      conserved region of the sex-determining gene on the Y-chromosome (Sry) and a
      region of the Fragile X mental retardation gene (Fmr-1). The multiplex nature of
      this protocol allows the determination of gender using the Sry marker with the
      Fmr-1 marker providing an internal control. This technique is applicable to the
      enforcement of the validation tag system for game species. Data are provided from
      a wildlife investigation in Ontario.

PMID- 9608688
TI  - Frequency of pubic hair transfer during sexual intercourse.
AB  - This study measured the frequency of pubic hair transfer between a limited number
      of consenting heterosexual partners. The results derive from controlled
      experiments with a number of human subjects rather than forensic casework.
      Standardized collection procedures were observed, situational variables were
      tracked. Participants (forensic laboratory employees and their spouses) were six
      Caucasian couples who collected their pubic hair combings immediately following
      intercourse. Subjects provided informed consent in accordance with the protocol
      for human subjects approved by the U.A.B. institutional review board. The
      experiment was replicated ten times for five couples, and five times for another
      couple (total n = 110). Transfer frequencies were calculated from instances where
      foreign (exogenous) hairs were observed. Results showed at least one exogenous
      pubic hair in 17.3% (19/110) of combings. Transfers to males (23.6%, or 13/55)
      were more prevalent than transfers to females (10.9%, or 6/55). Only once were
      transfers observed simultaneously between both male and female. A total of 28
      exogenous pubic hairs were identified. Subjects reported intercourse duration of
      2-25 min, intervening intervals of 1-240 h, pre-coital bathing intervals of 0.25
      24 h, and predominantly missionary position (76%). No clear relationship among
      these other survey variables was observed. The prevalence of female-to-male pubic
      hair transfers suggests the importance of collecting pubic hair combings from the
      male suspects as well as from female victims, provided the time interval is not
      extreme. Even under these optimum collection conditions, pubic hair transfers
      were observed only 17.3% of the time.

PMID- 9608689
TI  - Visualization of sebaceous fingerprints on fired cartridge cases: a laboratory
      study.
AB  - The visualization and endurance of fingerprints on cartridge cases after the
      firing process have been examined. Cartridges of M16, AK-47 (Kalashnikov) and
      Parabellum have been tested. Despite difficulties in visualizing these
      fingerprints, it was found that in some cartridge cases under laboratory
      conditions--for instance, on M16 brass cartridges--substantial parts of the
      fingerprints remain intact after shooting. The careful use of illumination after
      metal vapor deposition enabled visualization. Different possible mechanisms
      responsible for the partial destruction of the fingerprints are discussed.

PMID- 9608690
TI  - Malingering uncommon psychiatric symptoms among defendants charged under
      California's "three strikes and you're out" law.
AB  - This paper describes an epidemic of uncommon psychiatric symptoms among nine
      criminal defendants charged under California's new "Three Strikes and You're Out"
      law. The defendants were facing a minimum sentence of 25 years to life in prison.
      The defendants exhibited the following uncommon psychiatric symptoms: coprophagia
      (eating feces), eating cockroaches and many reported seeing little green men. The
      defendants, all of whom we believe were malingering, were evaluated by the
      authors for competency to stand trial. Thus far, eight of the nine defendants
      were found competent to stand trial; only one defendant was found incompetent to
      stand trial. The authors created a database which included information on the
      defendants from court documents and from our interview with the defendants. We
      summarized the data and outcomes of the case. Also included is a brief review of
      the "Three Strikes Law" and a paradigm for how we ruled out relevant psychiatric
      diagnoses before we arrived at our opinion of malingering.

PMID- 9608691
TI  - Bombing and psychopathy: an integrative review.
AB  - A review of the research on the motivations and behaviors of bombers is
      presented. The methodology consisted of a computer search of eight databases,
      book reviews, and telephonic interviews with local and federal law enforcement.
      The data were then compared to the substantial research on psychopathy. The
      authors conclude that a federally funded research effort is necessary, and should
      incorporate various structured interviews, history gathering, and psychological
      and physiological tests of incarcerated bombers, theoretically guided by the
      concordance between the known motivations and behavior of bombers and the
      concurrent and predictive validity of the construct, psychopathy.

PMID- 9608692
TI  - Criminal multilation of the human body in Sweden--a thirty-year medico-legal and
      forensic psychiatric study.
AB  - During the 30-year period 1961-1990, a total of 22 deaths with criminal
      multilation/dismemberment of the human body were registered in Sweden. The
      multilations occurred in time clusters, mostly during the summer and winter
      periods, and increased during the three decades, with incidence rates of 0.05,
      0.1, and 0.125 per million inhabitants and year, respectively. Multilation was
      noted 6.6 times more often in large urban areas than in the rest of Sweden.
      Defensive mutilation, in order to get rid of the corpse or make its identity more
      difficult, was noted in ten instances, aggressive mutilation following outrageous
      overkilling in four, offensive mutilation (lust murder) in seven, and necromanic
      multilation in one instance. In the last-mentioned case the cause of death was
      natural, while all deaths in the first three groups were homicidal, or homicide
      was strongly suspected. All perpetrators were males, in six instances assisted by
      other persons. In more than half of the cases the perpetrator's occupation was
      associated with application of anatomical knowledge, e.g., butcher, physician,
      veterinary assistant, or hunter. The perpetrators of the defensive and aggressive
      mutilations were mostly disorganized, i.e., alcoholics or drug users with
      previous psychiatric contacts and criminal histories, while the lust murderers
      were mostly organized, with a history of violent crimes (including the "serial
      killing" type), drug abuse and mental disorders with anxiety and schizophrenia,
      in that order to a diminishing degree. There were differences in mode of
      mutilation, depending on whether the mutilation was carried out by a layman, a
      butcher, or a physician. In only one case was the perpetrator convicted for the
      mutilation act itself; in the remaining instances the manslaughter, as a more
      serious crime, assimilated the mutilation. When the mutilation made it impossible
      to establish the cause of death, the perpetrators, despite strong circumstantial
      evidence indicating murder, were acquitted.

PMID- 9608693
TI  - Arthropod succession patterns onto burnt carrion in two contrasting habitats in
      the Hawaiian Islands.
AB  - Decomposition studies were conducted using carcasses of domestic pigs, Sus scrofa
      L., one burned and the other unburned (the control) to determine effects of
      burning on arthropod succession patterns. The burnt carcass corresponded to a CGS
      level #2 burn victim. The studies were conducted in two contrasting habitats,
      both on the island of Oahu. The first was conducted in a xerophytic habitat from
      1 Sept. 1995 through 1 Oct. 1995 while the second was conducted in a rainforest
      habitat from 29 April 1996 to 28 May 1996. No marked differences were noted in
      arthropod fauna present or the duration of the stages of decomposition between
      the carcasses at either site. The major oviposition by flies of the family
      Calliphoridae occurred one day earlier on the burnt carcass than the control
      carcass at Diamond Head and four days earlier at Lyon Arboretum. This resulted in
      all successional waves onto the burnt carcass occurring one day earlier at
      Diamond Head and four days earlier at Lyon Arboretum. These differences could
      alter a postmortem interval estimate based on arthropod succession patterns by up
      to 24 hours and 4 days, respectively.

PMID- 9608694
TI  - Stability of diltiazem in whole blood: forensic implications.
AB  - The stability of diltiazem (DTZ) in whole blood and in postmortem samples was
      investigated. In the first study, an aliquot of outdated Red Cross blood with
      sodium fluoride added as a preservative was spiked with DTZ and stored for one
      year under three separate conditions: room temperature, 4 degrees C, and -20
      degrees C. DTZ and one of its major metabolites, desacetyldiltiazem (DAD), were
      quantitated at given intervals during this period. In the second study, case
      postmortem blood samples (n = 36) that exhibited different degrees of
      putrefaction were spiked in a similar fashion and the stability of DTZ was
      determined after storage at 4 degrees C for 92 days. DTZ and DAD were extracted
      as bases, using mild pH conditions to prevent the hydrolysis of DTZ, and
      quantitated by an HPLC system equipped with a diode array detector and a
      Supelcosil LCDP column, 5 microns, 250 mm x 4.6 mm inside diameter. Approximately
      50% of DTZ was lost in the Red Cross blood stored at room temperature and 4
      degrees C, after 19 and 124 days, respectively. This was associated with
      concomitant appearance and comparable increase in DAD concentration, presumably
      due to the in vitro hydrolysis of DTZ to DAD. No significant loss of DTZ was
      observed in the -20 degrees C samples. Similar changes in DTZ and DAD
      concentrations were seen in postmortem blood samples stored at 4 degrees C for 92
      days, though notably, the extent of loss of DTZ varied from complete to
      negligible. The data suggest that the potential for in vitro conversion of DTZ to
      DAD should be considered for proper interpretation of postmortem DTZ/DAD
      findings. Several cases examined in this laboratory will be used to discuss other
      forensic implications.

PMID- 9608695
TI  - Comparison of anti-epileptic drug levels in different cases of sudden death.
AB  - Sudden unexplained death syndrome (SUDS) in epilepsy is identified as death in an
      epileptic individual with no anatomic cause found at autopsy. SUDS appears to be
      associated with subtherapeutic levels of anticonvulsants. Sudden death with no
      demonstrable cause at autopsy accounts for 5% to 30% of deaths in epileptic
      individuals. In the majority of cases, however, the cause of death in epileptic
      individuals can be demonstrated at autopsy. We examined the anti-epileptic drug
      concentrations in decedents who died as a direct result of epilepsy and compared
      these findings with those from a control population of epileptic patients who
      died suddenly due to some unrelated cause. This retrospective study was conducted
      on all deaths involving patients with epilepsy examined at the Jefferson County
      Coroner/Medical Examiner office from 1986-95. Out of 115 total cases the
      underlying cause of death was epilepsy in 60 cases--52 cases of SUDS and 8 deaths
      caused by an accident precipitated by a seizure. In 44 cases death was unrelated
      to the decedent's epilepsy. In 11 cases the contribution of epilepsy to death
      could not be determined. Published articles on SUDS report subtherapeutic anti
      epileptic medication levels in 63% to 94% of cases. We found subtherapeutic drug
      levels in 69% of the 52 cases of SUDS, in 75% of the 8 cases where a seizure
      precipitated an accident causing death, and in 34% of the control population. The
      incidence of subtherapeutic anticonvulsants is significantly greater in patients
      dying as a direct result of their epilepsy than in those dying of an unrelated
      cause.

PMID- 9608696
TI  - Electrolyte concentration differences between left and right vitreous humor
      samples.
AB  - Between-eye differences in electrolyte concentrations were studied in 200 medico
      legal autopsies using an ion-specific electrode system. Taking the highest of the
      paired vitreous potassium concentrations, cases < 15 mM/L were classified as
      biochemically nonputrefied (Cat.1, n = 124), cases 15 to 20 mM/L as early
      putrefaction (Cat.2, n = 51), and cases > 20 mM/L as biochemically putrefied
      (Cat.3, n = 25). Mean paired vitreous sodium for all cases (n = 200) was 112 to
      173 mM/L (mean 148, standard deviation (SD) = 8.9); between-eye differences were
      0 to 8 mM/L (0% to 5.1% of mean), averaging 1.5 mM/L (1%) and with only one case
      (in Cat.3) outside instrument accuracy (+/- 3 mM/L). Mean paired vitreous
      chloride for all cases was 73 to 124 mM/L (mean 109, SD = 7.8); between-eye
      differences were 0 to 9 mM/L (0% to 8.8% of mean), averaging 1.7 mM/L (1.5%) and
      with 5 of 200 cases outside instrument accuracy (+/- 3 mM/L). Thus between-eye
      concentration differences of sodium and chloride are tolerable using this
      methodology. Previous reports of greater variability likely reflect errors
      introduced by sample manipulation prior to analysis. By contrast, between-eye
      differences in potassium in Cat.1 cases were 0 to 2.34 mM/L (0% to 21.8% of mean)
      averaging 0.37 mM/L (3.3%). Significant and erratic between-eye differences in
      potassium undermine the usefulness of vitreous potassium in estimation of time of
      death.

PMID- 9608697
TI  - Ethics, Malingering, and a lie-detector at the bedside.
AB  - A psychiatric consultation is presented in which the physician uses a cardiac
      monitor in the manner of a lie-detector. Ethical analysis of a clinician's duties
      in cases of suspected malingering addresses both the standard of informed consent
      necessary for such assessments and the potential forensic consequences of
      unanticipated clinical findings.

PMID- 9608698
TI  - Factors associated with weapon use in maternal filicide.
AB  - The objective of this study was to identify factors associated with weapon use in
      a group of filicidal women. Clinical data were gathered from the charts of sixty
      filicidal women evaluated at Michigan's Center for Forensic Psychiatry or through
      Connecticut's Psychiatric Security Review Board from 1970 to 1996. Factors
      associated with weapon use were determined using chi squares, ANCOVAS, and a
      logistic regression. Results were compared to national statistics for child
      homicide from the Department of Justice Uniform Crime Reports (UCR). Weapon was
      defined as knife or gun for the study. Weapons were used by one of four women in
      our study. Guns were used by 13% of filicidal women and knives by 12%. Odds ratio
      showed that psychotic women were eleven times more likely to kill their child
      with a weapon than their non-psychotic counterparts (11.2; p = .008). Psychosis
      was present in every mother who killed her child with a knife and in seven of
      eight women who killed their children with a gun. Younger children were less
      likely to be killed with weapons (ANCOVA; F = 8.28; p = .006). This finding was
      independent of presence or absence of maternal psychosis. These results show that
      psychotic women are more likely than non-psychotic women to kill their children
      with weapons. They also show that mothers are more likely to use weapons to kill
      older children than younger children.

PMID- 9608699
TI  - Screening of pharmaceuticals and drugs in synovial fluid of the knee joint and in
      vitreous humor by fluorescence polarization immunoassay (FPIA).
AB  - The investigations presented are aimed at testing whether ABBOTT's fluorescence
      polarization immunoassays for identification of drugs of abuse and
      pharmaceuticals in serum and urine are applicable to knee joint synovial fluid
      and vitreous humor. The survey confirms the general applicability of the tests to
      the respective body fluids without previous precipitation, only after
      liquefaction using hyaluronidase. The calculated cross-reactivities are shown in
      tables.

PMID- 9608700
TI  - Automated extraction of lysergic acid diethylamide (LSD) and N-demethyl-LSD from
      blood, serum, plasma, and urine samples using the Zymark RapidTrace with LC/MS/MS
      confirmation.
AB  - A forensic procedure for the quantitative confirmation of lysergic acid
      diethylamide (LSD) and the qualitative confirmation of its metabolite, N-demethyl
      LSD, in blood, serum, plasma, and urine samples is presented. The Zymark
      RapidTrace was used to perform fully automated solid-phase extractions of all
      specimen types. After extract evaporation, confirmations were performed using
      liquid chromatography (LC) followed by positive electrospray ionization (ESI+)
      mass spectrometry/mass spectrometry (MS/MS) without derivatization. Quantitation
      of LSD was accomplished using LSD-d3 as an internal standard. The limit of
      quantitation (LOQ) for LSD was 0.05 ng/mL. The limit of detection (LOD) for both
      LSD and N-demethyl-LSD was 0.025 ng/mL. The recovery of LSD was greater than 95%
      at levels of 0.1 ng/mL and 2.0 ng/mL. For LSD at 1.0 ng/mL, the within-run and
      between-run (different day) relative standard deviation (RSD) was 2.2% and 4.4%,
      respectively.

PMID- 9608701
TI  - A convenient derivatization method for gas chromatography/mass spectrometric
      determination of phenmetrazine in urine using 2,2,2-trichloroethyl chloroformate.
AB  - Phenmetrazine is a central nervous system stimulant currently used as an
      anorectic agent. The drug is abused and is reported to cause death from overdose.
      We describe a new derivatization method for phenmetrazine using 2,2,2
      trichloroethyl chloroformate. Quantitation of urinary phenmetrazine can be easily
      achieved by using N-propylamphetamine as an internal standard. The phenmetrazine
      2,2,2-trichloroethyl carbamate showed a molecular ion isotope cluster at m/z 351,
      353, 355, and 357 (isotope effect of three chlorine atoms in the derivatized
      molecule) and other peaks at m/z 247, 245, 204, 114, and 70 in the electron
      ionization mass spectrometry, thus aiding in unambiguous identification. The
      underivatized phenmetrazine showed a relatively weaker molecular ion at m/z 177
      and a base peak at m/z 71. The N-propylamphetamine 2,2,2-trichloroethyl carbamate
      (internal standard) showed a very weak molecular ion at m/z 351 and a base peak
      at m/z 260. Another strong characteristic peak at m/z 91 was also observed. The
      retention time of derivatized phenmetrazine (9.5 min) was substantially longer
      than the retention time of the underivatized molecule (2.5 min). Moreover,
      underivatized phenmetrazine showed poor peak shape (substantial tailing) while
      derivatized phenmetrazine had excellent chromatographic property. The within-run
      and between-run precisions of the assay were 1.9% and 3.2% at a urinary
      phenmetrazine concentration of 20 micrograms/mL. The assay was linear for urinary
      phenmetrazine concentration of 1 microgram/mL to 100 micrograms/mL with a
      detection limit of 0.5 microgram/mL.

PMID- 9608702
TI  - Gas chromatography-electron ionization and chemical ionization mass spectrometric
      analysis of urinary phenmetrazine after derivatization with 4
      carbethoxyhexafluorobutyryl chloride--a new derivative.
AB  - Phenmetrazine is a central nervous system stimulant currently used as an
      anorectic agent. The drug is abused and is reported to cause death from overdose.
      We describe a new derivatization method for phenmetrazine using 4
      carbethoxyhexafluorobutyryl chloride. Quantitation of urinary phenmetrazine can
      be easily achieved by using N-ethyl amphetamine as an internal standard. The
      electron ionization mass spectrum of 4-carbethoxyhexafluorobutyryl derivative of
      phenmetrazine showed a molecular ion at m/z 427 and a base peak at m/z 70. In the
      methane chemical ionization mass spectrum, the base peak was observed at m/z 428
      (protonated molecular ion). In the electron ionization mass spectrum of 4
      carbethoxyhexafluorobutyryl derivative of the internal standard, N-ethyl
      amphetamine we did not observe a molecular ion. However, in the chemical
      ionization mass spectrum, the protonated molecular ion at m/z 414 was the base
      peak. The retention time of derivatized phenmetrazine (8.4 min) was substantially
      longer than the retention time of the underivatized molecule. Moreover,
      underivatized phenmetrazine showed poor peak shape (substantial tailing) while
      derivatized phenmetrazine had excellent chromatographic properties. The within
      run and between-run precisions of the assay were 2.6% and 3.1% respectively at a
      urinary phenmetrazine concentration of 10 micrograms/mL. The assay was linear for
      urinary phenmetrazine concentration of 1 to 100 micrograms/mL with a detection
      limit of 0.2 microgram/mL.

PMID- 9608703
TI  - DNA typing of human dandruff.
AB  - Dandruff particles contain a considerable portion of nucleated cells within the
      aggregates of nuclei-free corneocytes. The nuclei could be partially degraded due
      to epidermal differentiation processes. To test the suitability of DNA from
      dandruff for forensic application, a study of 35 subjects and two crime cases has
      been carried out using different STR polymorphisms. In 90% of the samples DNA
      genotyping could be easily performed indicating that DNA from dandruff is at
      least suitable for STR analysis. DNA quantity per dandruff particle varies
      extremely within a range from 0.8 to 16.6 ng DNA for the tested subjects.
      Genotyping was also possible for a single dandruff particle if DNA extraction
      volume had been reduced. In mixed samples from dandruff coextracted with
      bloodstains or semen stains dandruff genotype was detectable. in some cases.
      These results demonstrate the relevance of dandruff in forensic casework either
      as an additional sample or as a source of inadvertent contamination.

PMID- 9608704
TI  - Subtyping of the HLA-DQA1 locus and independence testing with PM and STR/VNTR
      loci.
AB  - Allele and genotype frequencies for six loci (HLA-DQA1 and PM loci) were
      determined in African Americans, United States Caucasians, and Southwestern
      Hispanics. The data include allele frequencies of the HLA-DQA1 4 subtypes. The
      HLA-DQA1 4 allele subtyping affords greater power of discrimination in African
      Americans and Southwestern Hispanics than in Caucasians, due to the relatively
      lower 4.2/4.3 allele frequency in Caucasians. Based on the exact test, all loci,
      except the GYPA locus in the African American sample (p = 0.011), meet Hardy
      Weinberg expectations. There were two examples of significant departures from
      expectations of independence between alleles of the HLA-DQA1 and PM loci (HBGG/Gc
      in African Americans, p = 0.30; LDLR/DQA1 in Caucasians, p = 0.023). The HLA-DQA1
      and PM loci also were tested for associations with three STR loci and the DIS80
      locus. There were four examples of significant departures from expectations of
      independence (TPOX/D7S8 and THO1/HBGG in African Americans, p = 0.035 and 0.028,
      respectively; THO1/LDLR in Caucasians, p = 0.028; and GYPA/D1S80 in Hispanics, p
      = 0.046). The HLA-DQA1 and PM allele frequency data were compared with previously
      reported data on other sample populations of the same population categories from
      our laboratory; the allele frequencies at all loci, except the D7S8 locus in
      Hispanics (p = 0.028), were statistically similar. The frequency data can be used
      in forensic analyses and paternity tests to estimate the frequency of a multiple
      locus DNA profile in various general United States populations.

PMID- 9608705
TI  - Greek Cypriot allele and genotype frequencies for Amplitype PM-DQA1 and D1S80
      loci.
AB  - A sample from the Greek Cypriot population was typed at seven forensically
      important PCR-based loci: LDLR, GYPA, HBGG, D7S8, GC, HLA-DQA1, and D1S80. The
      results showed that all loci meet Hardy-Weinberg expectations and that there is
      no evidence for association of alleles between loci. Allelic frequency
      distributions at all loci, except HLA-DQA1 and two D1S80 alleles, were similar to
      those of U.S. Caucasians. Greek Cypriot population databases have been created
      and can be used for forensic analyses to estimate the frequency of a multiple
      locus DNA profile.

PMID- 9608706
TI  - An illustrated guide to RFLP troubleshooting.
AB  - A large number of reagents and steps are required for restriction fragment length
      polymorphism (RFLP) analysis, which at times make determining the cause of any
      observed anomaly difficult. Troubleshooting problems in RFLP analysis is
      difficult and often the exact cause of a problem cannot be determined. In this
      paper a collection of controlled experiments detail the consequences of a number
      of human or materials problems. Although the focus is on forensic applications,
      this troubleshooting guide will be helpful to anyone employing Southern analysis.

PMID- 9608707
TI  - Identification of zinc phosphide in a falsely labeled rodenticide bait.
AB  - "Kela" is a commercial rodenticide bait commonly used in Israel, made of wheat
      grains, which, according to its label, contains chlorophacinone. This product was
      involved in the death case of a man in which the victim's female companion was
      accused of assisting in this suicide and was subsequently convicted. Analysis of
      the wheat grains revealed zinc phosphide, whose use is restricted to authorized
      exterminators only, instead of chlorophacinone. Zinc phosphide was identified
      using microscopic examination, scanning electron microscopy/energy dispersive X
      ray spectroscopy (SEM/EDX) and X-ray powder diffraction (XRD).

PMID- 9608708
TI  - Use of nested PCR to identify charred human remains and minute amounts of blood.
AB  - Reliable single cell PCR requires nested or heminested PCR and careful
      optimization of conditions. This report describes the successful use of nested
      PCR for gender identification and reverse paternity testing in a forensic case
      where the only available materials consisted of charred human remains and a
      minute quantity of blood that were unsuitable for standard PCR. Use of nested PCR
      allowed the blood and burned tissue to be identified as human female. Analysis of
      two PCR length polymorphisms (AMPFLP) was successful on the blood sample and
      reverse paternity testing yielded a 98% probability that the blood spot was from
      the victim. The defendant was convicted of murder following a bench trial and the
      verdict was upheld by the Appellate court.

PMID- 9608710
TI  - An unusual case of multiple mesosternal foramina.
AB  - We present an unusual example of multiple mesosternal foramina (MMF). The
      alignment of the paired defects is unlike any previously described. Although
      single sternal defects are often encountered, paired defects are quite uncommon.
      This is the first documented example of bilateral paired defects in the sternum.

PMID- 9608709
TI  - Maternal identification from skeletal remains of an infant kept by the alleged
      mother for 16 years with DNA typing.
AB  - This is a case study concerning maternal identification by DNA typing at various
      loci. An infant skeleton was found in the alleged mother's apartment after it was
      kept for 16 years. We obtained the skeletal remains as well as saliva stains from
      the alleged mother. DNA typing was conducted for three loci in the HLA class II
      region (HLA-DQA1, -DPB1, and DRB1), five loci with the AmpliType PM kit (LDLR,
      GYPA, HBGG, D7S8, and GC), five STR loci (LPL, vWA, F13B, TH01, and TPOX) and D
      loop region in mtDNA for maternal identification. Sex determination was
      accomplished using fluorescent DNA capillary electrophoresis typing.
      Approximately 5 ng of human DNA was recovered from 1 g of femur bone retrieved
      from the infant skeletal remains. The probability of two unrelated Japanese
      sharing the same genotypes was estimated as 7.2 x 10(-11). The combined
      probability of exclusion that an individual is not the mother was also calculated
      at 0.998. We therefore conclude that the skeleton is from a female infant, and
      that there is no inconsistency in the claim that the infant was a daughter of the
      alleged mother.

PMID- 9608711
TI  - Sudden unexpected death resulting from an anomalous hypoplastic left coronary
      artery.
AB  - We present a case of sudden death in a 24-year-old, healthy white female who was
      physically active and participated in sports, including soccer. Two weeks prior
      to her death, an insurance physical examination revealed an abnormal
      electrocardiogram which demonstrated flipped T waves in the anterior leads. There
      was no other remarkable medical history. At autopsy, only one coronary ostium was
      demonstrated and it originated from the right aortic sinus. Approximately 0.8 cm
      from this right coronary artery (RCA) ostium, a left coronary artery (LCA)
      branched off the RCA at a 90-degree angle. The LCA had luminal diameter of 0.4 m
      but the LCA had a luminal diameter of only 0.1 cm. The LCA coursed anterior to
      the base of the pulmonary artery and down the anterior ventricular septum
      reflecting the usual course of the left anterior descending (LAD) coronary
      artery. The LCA and RCA paths appeared to merge or terminate at the anterior left
      ventricular myocardium which was discolored gray, a process that involved the
      inner and middle thirds of the myocardium. Based on the autopsy findings, we
      certified the cause of death as a probable arrhythmia due to myocardial fibrosis
      and dystrophic calcification resulting from complications of an anomalous
      hypoplastic left coronary artery. Anomalies of coronary arteries have been
      classified and studied at autopsy and by clinical angiography. Coronary artery
      anomalies can be divided into minor and major forms with major anomalies often
      resulting in cardiac dysfunction that may cause failure and death. Minor
      anomalies, in general, have no pathophysiological significance and are compatible
      with life. Minor anomalies include variations in number and location of coronary
      ostia. A single coronary ostia is exceedingly rare in hearts with no other
      congenital malformations. The prognostic significance can be unpredictable. A
      single coronary artery has the potential to be dangerous if obstructed at its
      main stem, or if it branches at an acute angle. Additionally, hypoplasia of one
      or more coronary arteries has been found to be associated with sudden death.

PMID- 9608712
TI  - 9 mm ammunition used in a 40 caliber glock pistol: an atypical gunshot wound.
AB  - Atypical gunshot wounds due to ricochet and intermediate targets have been well
      described in the literature. We represent a case of suicide with an atypical
      entrance wound and bullet without rifling marks due to 9 mm ammunition being
      loaded and fired from a 40 caliber semiautomatic pistol.

PMID- 9608713
TI  - Cardiac sarcoidosis--an occult cause of sudden death: a case report and
      literature review.
AB  - Sarcoidosis is a multi-systemic granulomatous disease of unknown cause. It
      commonly involves lymph nodes, lungs, eyes, and skin. Cardiac sarcoid may be
      isolated, or associated with systemic involvement. Cardiac involvement is found
      in 20-50% of autopsied patients with sarcoidosis. However, it only gives rise to
      clinical manifestations in about 5% of patients. Cardiac involvement by sarcoid
      has been reported to manifest as complete heart block, papillary muscle
      dysfunction, congestive heart failure, pericarditis and/or effusion, conduction
      abnormality or arrhythmia, chest pain, and sudden death. The most common site of
      involvement is the interventricular septum base, which when involved may lead to
      heart block or arrhythmia. We report a case of sudden death in a 33-year-old male
      with a history of surgically repaired congenital heart disease. Although his
      congenital heart disease was originally postulated to be important in his death,
      autopsy examination revealed cardiac sarcoid with prominent involvement of the
      conduction system.

PMID- 9608714
TI  - Absorption of intubation-related lidocaine from the trachea during prolonged
      cardiopulmonary resuscitation.
AB  - The purpose of this study was to determine whether lidocaine is absorbed from the
      trachea during the artificial circulation of cardiopulmonary resuscitation. The
      tissue distribution of lidocaine was investigated in eight individuals (Cases 1
      8) who underwent cardiopulmonary resuscitation before being pronounced dead. In
      Cases 1-4, there was no restoration of heart beat during cardiopulmonary
      resuscitation. Heart massage had been continued for 5 min in Cases 1 and 2, and
      for 60 min in Cases 3 and 4. Relatively high concentrations of lidocaine (more
      than 0.1 mg/L) were detected in the blood left in the heart and/or in the large
      thoracic vessels in the four cases. In Cases 1-3, a large proportion of the
      lidocaine detected in these blood samples may have diffused from the trachea
      after cessation of cardiopulmonary resuscitation since no lidocaine was detected
      in the cerebrospinal fluid, cerebrum, liver, right kidney, and/or right femoral
      muscle. In Case 4, however, tracheal lidocaine was thought to have been absorbed
      during cardiopulmonary resuscitation because 0.167-0.340 mg/L or mg/kg lidocaine
      was detected in the cerebrospinal fluid, liver, right kidney, and right femoral
      muscle. This was substantiated in experiments performed in rabbit carcasses given
      50 microL/kg Xylocaine jelly (a 2% lidocaine hydrochloride preparation)
      intratracheally, followed by rhythmical thoracic compressions (100-150 times per
      minute) for 60 min. A possible reason for lack of absorption of lidocaine from
      the trachea of Case 3 during a 60-min cardiopulmonary resuscitation procedure may
      have been that effective blood circulation was not obtained during
      cardiopulmonary resuscitation because of bleeding and pulmonary collapse. Cases 5
      8 survived for 3 h to 10 days after successful cardiopulmonary resuscitation; it
      was obvious that lidocaine was distributed to the tissues under the influence of
      the natural circulation. The kidney to liver lidocaine ratio in Case 4 (0.8) was
      much lower than that in Cases 5-8 (1.3-4.6), although the lidocaine ratio in the
      blood in the left ventricle when compared to blood in the right ventricle was
      similar in the five cases. The kidney to liver lidocaine ratio may be helpful in
      judging whether the lidocaine detected was absorbed during the artificial
      circulation of cardiopulmonary resuscitation or naturally. Additionally,
      postmortem diffusion of tracheal lidocaine into the blood in the left ventricle
      was much greater than into the blood in the right ventricle due to their
      anatomical location during a supine position. The pattern of tissue distribution
      of lidocaine gives useful information on the state of decedents during
      cardiopulmonary resuscitation.

PMID- 9608715
TI  - Interval duration between injury and severe symptoms in nonaccidental head trauma
      in infants and young children.
AB  - Forensic pathologists are frequently asked to describe the interval between
      injury and the onset of symptoms in child abuse head injury deaths. A
      prospective, postmortem study examined the interval between injury and onset of
      symptoms in 76 head injury deaths in which this information was available. The
      head injury deaths were divided by mechanism of injury. The mechanisms were shake
      (no impact), combined shake and blunt impact, and blunt impact (no history of
      shaking). The interval was less than 24 hours in 80% of shakes, 71.9% of
      combined, and 69.2% of blunt injuries. The interval was greater than 24 hours in
      more than 25% of each of these latter groups and was more than 72 hours in four
      children. The variable intervals between injury and severe symptoms warrant
      circumspection in describing the interval for investigators or triers of fact. It
      should be noted that in all of the cases where information was supplied by
      someone other than the perpetrator, the child was not normal during the interval.

PMID- 9608716
TI  - A fatal case of fungal endocarditis of the tricuspid valve associated with long
      term venous catheterization and treatment with antibiotics in a patient with a
      history of alcohol abuse.
AB  - We report a fatal case of fungal (candidal) endocarditis of the tricuspid valve
      with clinico-pathologically interesting findings following and associated with
      candidal pneumonia during long-term central venous catheterization (CVC) for
      intravenous therapy and long-term treatment with antibiotics for bacterial and
      fungal infection in a patient with a history of alcohol abuse. We review the
      literature on fungal cardiac infection related to long-term catheterization and
      alcohol abuse, and discuss the pathogenesis.

PMID- 9608717
TI  - Protein profiles of Malassezia pachydermatis isolated from dogs.
AB  - The protein fractions of 30 Malassezia pachydermatis isolates from dogs (15 with
      otitis and 15 with dermatitis) were investigated by sodium dodecyl sulphate
      polyacrylamide gel electrophoresis (SDS-PAGE). The electrophoresis runs resulted
      in bands ranging from 15.0-145.7 kDa in the ear canal secretion isolates. The
      values for the skin isolates varied between 16.0-141.1 kDa. The presence of
      protein bands occurred most frequently within the 30-40 kDa bands (66.7%), 40-50
      kDa (70.0%), 50-60 kDa (73.3%) and 80-90 kDa (83.3%). No statistical differences
      were determined, considering the behavior of M. pachydermatis isolates from ear
      and skin in each band of molecular weight values, nor in the number of bands
      obtained.

PMID- 9608718
TI  - Keratinolysis by poultry farm soil fungi.
AB  - Species of Chrysosporium, Malbranchea, Scopulariopsis, Microascus, and
      Gliocladium isolated from poultry farm soils were grown on two keratin media. All
      the test fungi could grow on keratin (human hair) and degrade it, releasing
      sulphydryl-containing compounds detected as extracellular keratinase, cysteine
      and total proteins. Glucose supplemented keratin medium supported maximum
      keratinolysis. Keratinase activity also changed the pH of the medium towards
      alkalinity and species with strong keratinolytic ability were noted to render the
      culture medium more alkaline than those that were less kiratinolytic.

PMID- 9608719
TI  - The invasive behaviour of Cryptococcus neoformans: a possibility of direct access
      to the central nervous system?
AB  - Cryptococcocal meningoencephalitis is always considered secondary to initial lung
      infection. Because of the unquestionable evidence of haematogenious spread from
      the lungs, few publications have reported about other possible primary sites of
      infection or other routes to the central nervous system. This study was designed
      to investigate the infiltrative pattern of C. neoformans in immunocompromised
      mice by treatment with dexamethasone. The infection was performed by nasal
      instillation (30 mice) or injection into the retro-orbital space (12 mice). From
      the group infected intranasally, 3 mice presented diffuse invasive fungal
      colonisation of the mucosa and submucosa. The histologic findings showed
      infiltrative growth along the periosteum, sometimes surrounded nervous endings of
      submucosa, invasion along the olfactory nerve and simultaneous meningeal
      involvement in 2 mice on the 6th and 8th day of infection. All mice infected into
      the retro-ocular space developed lesions containing numerous cryptococci in the
      local of the inoculum. Out of the main lesion we observed preferential growth
      along the perineural spaces with adherence to the perineurium, perivascular
      spaces and sometimes along aponeurosis. Simultaneous invasion of trigeminal
      ganglio and trigeminal branches was observed in 4 mice. These morphologic
      patterns suggest the hypothesis of direct infiltrative invasion of the central
      nervous system.

PMID- 9608720
TI  - Cryptococcosis associated with AIDS in the Muniz Hospital of Buenos Aires.
AB  - Some epidemiologic, diagnostic and immunologic aspects of 93 (75 males and 18
      women) cases of cryptococcosis (CRY) associated with AIDS, hospitalized in the
      Muniz Hospital (MH) in Buenos Aires during 1994, were retrospectively studied.
      The median age (MA) of the patients under study was 28 years (17-49 y); 30 (17
      49) y for males and 23 (22-34) y for women. Intravenous drug addiction (34% of
      patients) and homo/bisexuality in men (17%) were the most frequent risk factors
      for HIV infection. The MA of these groups were 27.5 (17-41) y and 34 (25-41) y,
      respectively. Microscopic CSF examination with India ink and the blood cultures
      (lysis-centrifugation) achieved the diagnosis of CRY in 67 (72%) and 16 (17%)
      patients, respectively. At diagnosis, the median titers for Cryptococcus
      neoformans capsular antigen were 1/1,000, 1/100 and 1/1 in serum, CSF and urine,
      respectively. Sixty five strains of C. neoformans were insolated from clinical
      samples; all were identified at variety neoformans employing the culture medium
      proposed by Salkin & Hurd and the D-proline assimilation test. At diagnosis, CD4+
      lymphocytes counts were < 50/microliter in 46 patients (83.63%), and were between
      51 and 200/microliter in 9 (16.4%). The CD4+/CD8+ ratio was < 1 in all patients.
      Most patients were born (83%) and lived at diagnosis (96%) in Buenos Aires (Bs
      As) city, Bs As outskirts towns and cities located in Bs As province.

PMID- 9608721
TI  - Interactions of F1 fractions from different strains of Paracoccidioides
      brasiliensis with human complement and with human neutrophils.
AB  - The aim of our study was to investigate differences that might exist in the
      activation of the human complement system by F1 fractions from four different
      isolates of P. brasiliensis. Isolates HC and 18 (virulent), 265 (low virulence),
      and 9 (intermediate virulence, attenuated) were used; before the experiments, the
      virulence of isolates HC and 18 was recovered by in vivo passage in guinea pigs.
      The four isolates of the fungus were processed for purification of F1 fractions
      and the activation of the human complement system was studied by a kinetic method
      of hemolytic activity measurement. The incubation of F1 fractions in normal human
      serum resulted in different degrees of inhibition of the classical and
      alternative pathways. The F1 fraction from the low virulence isolate was more
      efficient than the F1 fraction from the virulent isolates (HC and 18). Previous
      absorption of sera with F1 fractions completely abolished classical pathway
      activation. Using zymosan, instead of F1, in the absorption process caused the
      same phenomenon, suggesting that natural or nonspecific antibodies are
      responsible for the classical pathway activation. The alternative pathway
      activation did not depend on these antibodies, but was enhanced by their
      presence. On the other hand, F1 fractions from virulent isolates were more active
      in the stimulation of neutrophil chemiluminescence compared with the F1 fraction
      from the low virulence isolate. Whole P. brasiliensis yeast cells (WYC) from two
      distinct strains, 18 and 265, showed the same patterns of response of those
      observed with the F1 fractions in the functions tested. These differences in the
      behavior of the F1 fractions as well as WYC in relation to human complement
      activation and consequently to neutrophil stimulation may correlate with the
      virulence of individual isolates and may contribute to the understanding of the
      inflammatory response generation and maintenance processes in
      paracoccidioidomycosis.

PMID- 9608722
TI  - Palpebral paracoccidioidomycosis.
AB  - This paper describes two cases of eyelid paracoccidioidomycosis (South American
      blastomycosis) in which it was the first signal of the disease. In both cases the
      first clinical diagnosis made was not a fungal infection, but a neoplastic
      disease that was not confirmed by the pathology study. In the first patient we
      suspected a primary infection on the eyelid, because there was no other systemic
      signs of the disease, and in the second patient we noted a very advanced
      pulmonary lesions caused by the Paracoccidioides brasiliensis. We believe that,
      in endemic areas, the histopathological study should be made before every
      excisional procedures to avoid unnecessary palpebral mutilation.

PMID- 9608723
TI  - Ribosomal variation in six species of Fusarium.
AB  - Eighteen isolates representing six Fusarium species from diverse hosts and
      geographical origins were evaluated to determine ribosomal DNA variation using
      polymerase chain reaction and restriction fragment length polymorphisms. No
      length variation was observed for amplified 18S and 28S regions. However,
      amplification of the ITS region showed one isolate, a F. oxysporum, to be about
      120 bp larger than the remaining 17. Restriction digestions in the 18S region
      revealed polymorphisms within species of F. oxysporum and F. solani. An amplified
      variable stretch of the 28S gene showed restriction site differences between F.
      avenecum, F. sambucinum and F. sporotrichioides. A large degree of polymorphism
      was observed both between and within species in the ITS region. Therefore, entire
      sequences of the ITS and the 5.8S subunit were obtained for 17 of the 18
      isolates. These sequences, along with those from eight additional isolates, were
      analysed using PAUP to assess the occurrence of DNA sequence divergence within
      the ITS region. The lack of correlation between molecular-based relationships and
      species affinities inferred from morphology for some isolates indicates that
      species designation can be unreliable using morphological data alone. Possible
      reasons for the discordance of the sequence and morphological data are discussed.

PMID- 9608724
TI  - Characterization of epoxide hydrolase activity in Alternaria alternata f. sp.
      lycopersici. Possible involvement in toxin production.
AB  - Using trans-diphenylpropane oxide (tDPPO) as a substrate, we measured epoxide
      hydrolase (EH) activity in subcellular fractions of Alternaria alternata f. sp.
      lycopersici (Aal), a fungus that produces host-specific toxins. The activity was
      mainly (> 99.5%) located in the soluble fraction (100,000 x g supernatant) with
      the optimum pH at 7.4. An increase of toxin production between days 3 and 9 found
      in a Aal liquid culture over a 15 days period was concomitant with a period of
      high EH activity. EH activity remained constant during the same period in an
      Alternaria alternata culture, a fungus which does not produce toxin. In vivo
      treatment of Aal culture with the peroxisome proliferator clofibrate stimulated
      EH activity by 83% and enhanced toxin production 6.3 fold. Both 4-fluorochalcone
      oxide (4-FCO) and (2S,3S)-(-)-3-(4-nitrophenyl)-glycidol (SS-NPG) inhibited EH
      activity in vitro with a I50 of 23 +/- 1 microM and 72 +/- 19 microM,
      respectively. The possible physiological substrate 9,10-epoxystearic acid was
      hydrolyzed more efficiently by Aal sEH than the model substrates trans- and cis
      stilbene oxide (TSO and CSO) and trans- and cis-diphenylpropane oxide (tDPPO and
      cDPPO).

PMID- 9608725
TI  - In vitro effects of diacetoxyscirpenol (DAS) on human and rat granulo-monocytic
      progenitors.
AB  - Diacetoxyscirpenol (DAS) is a trichothecene mycotoxin produced by various species
      of fungi. Trichothecenes are known as major contaminants of cereals and cereal
      containing foods. DAS has been detected in agricultural products worldwide and
      persists in products after processing. In human as well as in animals, DAS
      consumption has been shown to induce haematological disorders (neutropenia,
      aplastic anemia). Granulo-monocytic progenitors (CFU-GM) from human umbilical
      cord blood and rat bone marrow have been cultured in the presence of DAS (from
      10(-8) M to 5 x 10(-10) M) for 14 days. Study of concentration and effect
      relationships have shown a sharp effect of DAS on rat CFU-GM between 10(-7) M and
      10(-8) M, while human CFU-GM are able to grow in the presence of 10(-8) M of the
      toxin. IC50 values on day 14 are respectively, 7.6 x 10(-9) M for human CFU-GM
      and 6.2 x 10(-9) M for rat CFU-GM.

PMID- 9608727
TI  - The spatial region of integration for visual symmetry detection.
AB  - Symmetry is a complex image property that is exploited by a sufficiently wide
      range of species to indicate that it is detected using simple visual mechanisms.
      These mechanisms rely on measurements made close to the axis of symmetry. We
      investigated the size and shape of this integration region (IR) by measuring
      human detection of spatially band-pass symmetrical patches embedded in noise.
      Resistance to disruption of symmetry (in the form of random phase noise) improves
      with increasing patch size, and then asymptotes when the embedded region fills
      the IR. The size of the IR is shown to vary in inverse proportion to spatial
      frequency; i.e. symmetry detection exhibits scale invariance. The IR is shown to
      have rigid dimensions, elongated in the direction of the axis of symmetry, with
      an aspect ratio of ca. 2:1. These results are consistent with a central role for
      spatial filtering in symmetry detection.

PMID- 9608726
TI  - Experience-dependent modulation of tonotopic neural responses in human auditory
      cortex.
AB  - Experience-dependent plasticity of receptive fields in the auditory cortex has
      been demonstrated by electrophysiological experiments in animals. In the present
      study we used PET neuroimaging to measure regional brain activity in volunteer
      human subjects during discriminatory classical conditioning of high (8000 Hz) or
      low (200 Hz) frequency tones by an aversive 100 dB white noise burst.
      Conditioning-related, frequency-specific modulation of tonotopic neural responses
      in the auditory cortex was observed. The modulated regions of the auditory cortex
      positively covaried with activity in the amygdala, basal forebrain and
      orbitofrontal cortex, and showed context-specific functional interactions with
      the medial geniculate nucleus. These results accord with animal single-unit data
      and support neurobiological models of auditory conditioning and value-dependent
      neural selection.

PMID- 9608728
TI  - Identification of Ca(2+)-activated K+ channel splice variants and their
      distribution in the turtle cochlea.
AB  - Turtle auditory-hair cells are frequency-tuned by the activity of calcium
      activated potassium (KCa) channels, a cell's characteristic frequency being
      determined by the KCa channel density and kinetics which both vary systematically
      along the cochlea. As a first step towards identifying the source of KCa channel
      variation, we have isolated, by reverse-transcription polymerase chain reaction
      on dissociated hair cells, the main cDNAs homologous to the slo gene which
      encodes the channel's alpha-subunit. A total of six alternatively spliced
      variants were identified, the smallest of which is 94% identical to a mouse Slo
      sequence. Variation occurs by insertion of exons at only two splice sites, two of
      these exons encoding novel 31- and 61-amino acid sequences. As we were unable to
      detect splicing at other potential sites, we infer that the six variants
      correspond to naturally occurring combinations. The spatial distribution of the
      variants, defined by isolating hair cells from different regions of the cochlea,
      indicated that some isoforms were non-uniformly distributed. Those containing
      large inserts in the first splice site were notably absent from the highest
      frequency region. We suggest that alternative splicing of the slo gene may
      contribute to variation in KCa channel properties.

PMID- 9608729
TI  - The role of parasite-induced immunodepression, rank and social environment in the
      modulation of behaviour and hormone concentration in male laboratory mice (Mus
      musculus).
AB  - Peripheral immune responsiveness in male laboratory mice was reduced by infection
      with the trichostrongyloid nematode Heligmosomoides polygyrus. Responsiveness was
      also lower among high-ranking (aggressive) males regardless of infection status.
      Reduced responsiveness in both infected animals and high rankers was associated
      with elevated serum corticosterone concentration (a potential immunodepressant)
      and was compounded among high-ranking males by subsequent high aggressiveness. As
      in previous experiments, only low rankers modulated testosterone secretion in
      relation to current immunocompetence and corticosterone concentration. The lack
      of any downregulation of aggression in response to parasite-induced
      immunodepression contrasted with previous results using antithymocyte serum and
      may be due to the more localized nature of immunodepression during H. polygyrus
      infection. However, the additional increase in corticosterone concentration
      resulting from exposure to female odour and destabilized aggressive social
      relationships did result in downregulation of aggression among high rankers and
      of testosterone among mice generally, suggesting that modulation rules of thumb
      are at least partly dependent on the proximate cues associated with
      immunodepression.

PMID- 9608730
TI  - The population genetic structure of the facultatively sexual parasitic nematode
      Strongyloides ratti in wild rats.
AB  - We have investigated the population genetic structure of the parasitic nematode
      Strongyloides ratti in wild rats. In the UK, S. ratti reproduces predominantly by
      mitotic parthenogenesis, with sexual forms present at a rate of less than 1%. S.
      ratti was found to be a prevalent parasite and substantial genetic diversity was
      detected. Most rats were infected with a genotypic mixture of parasites. A
      hierarchical analysis of the genetic variation found in S. ratti sampled across
      Britain and Germany showed that 73.3% was explained by variation between
      parasites within individual hosts and 25.3% by variation between rats within
      sample sites. Only a small proportion (1.4%) of the total genetic variation was
      attributable to genetic subdivision between sample sites, suggesting that there
      is substantial gene flow between these sites. Most parasites sampled were found
      to exist in Hardy-Weinberg equilibrium and this population genetic structure is
      discussed in view of the virtual absence of sexual reproduction.

PMID- 9608731
TI  - MHC-genotype of progeny influenced by parental infection.
AB  - In a previous series of in vitro fertilization experiments with mice we found non
      random combination of major histocompatibility complex (MHC) haplotypes in the
      very early embryos. Our results suggested that two selection mechanisms were
      operating: (i) the eggs selected specific sperm; and (ii) the second meiotic
      division in the eggs was influenced by the type of sperm that entered the egg.
      Furthermore, the proportion of MHC-heterozygous embryos varied over time,
      suggesting that non-random fertilization was dependent on an external factor that
      changed over time. As a higher frequency of heterozygous individuals correlated
      with an uncontrolled epidemic by MHV (mouse hepatitis virus), we suggested that
      MHV-infection might have influenced the outcome of fertilization. Here, we
      present an experiment that tests this hypothesis. We infected randomly chosen
      mice with MHV and sham-infected control mice five days before pairing. We
      recovered the two-cell embryos from the oviduct, cultured them until the
      blastocyst stage, and determined the genotype of each resulting blastocyst by
      polymerase chain reaction. We found the pattern that we expected from our
      previous experiments: virus-infected mice produced more MHC-heterozygous embryos
      than sham-infected ones. This suggests that parents are able to promote specific
      combinations of MHC-haplotypes during fertilization according to the presence or
      absence of a viral infection.

PMID- 9608732
TI  - The neurobiology of depression.

PMID- 9608733
TI  - Defibrillation: the spark of life.

PMID- 9608734
TI  - 2D 1H and 13C NMR evidence for stereoselective formation of a new bond C-N, C-S
      or C-C in the reaction of ivalin acetate with substituted pyrimidines.
AB  - Several pyrimidine derivatives of ivalin acetate were synthesized as potential
      anti HIV agents. High stereoselective Michael addition to ivaline acetate was
      observed and a new C-C, C-N or C-S bond was formed. 2D NMR 1H and 13C as well as
      X-ray crystallographic studies were performed on the compounds herein described
      to establish the structure and stereochemistry.

PMID- 9608735
TI  - Insect resistance of transgenic tobacco expressing an insect chitinase gene.
AB  - Chitinase expression in the insect gut normally occurs only during moulting,
      where the chitin of the peritrophic membrane is presumably degraded. Thus,
      insects feeding on plants that constitutively express an insect chitinase gene
      might be adversely affected, owing to an inappropriately timed exposure to
      chitinase. This hypothesis was tested by introducing a cDNA encoding a tobacco
      hornworm (Manduca sexta) chitinase (EC 3.2.1.14) into tobacco via Agrobacterium
      tumefaciens-mediated transformation. A truncated but enzymatically active
      chitinase was present in plants expressing the gene. Segregating progeny of high
      expressing plants were compared for their ability to support growth of tobacco
      budworm (Heliothis virescens) larvae and for feeding damage. Both parameters were
      significantly reduced when budworms fed on transgenic tobacco plants expressing
      high levels of the chitinase gene. In contrast, hornworm larvae showed no
      significant growth reduction when fed on the chitinase-expressing transgenics.
      However, both budworm and hornworm larvae, when fed on chitinase-expressing
      transgenic plants coated with sublethal concentrations of a Bacillus
      thuringiensis toxin, were significantly stunted relative to larvae fed on toxin
      treated non-transgenic controls. Foliar damage was also reduced. Plants
      expressing an insect chitinase gene may have agronomic potential for insect
      control.

PMID- 9608736
TI  - Cloning and sequencing of the CRABP-I locus from chicken and pufferfish: analysis
      of the promoter regions in transgenic mice.
AB  - Retinoic acid (RA), a derivative of vitamin A, is an important molecule for
      development and homeostasis of vertebrate organisms. The intracellular retinoic
      acid binding protein CRABP-I has a high affinity for RA, and is thought to be
      involved in the mechanism of RA signalling. CRABP-I is well conserved in
      evolution and shows a specific expression pattern during development, but mice
      made deficient for the protein by gene targeting appear normal. However, the high
      degree of homology with CRABP-I from other species indicates that the protein has
      been subject to strong selective conservation, indicative of an important
      biological function. In this paper we have compared the conservation in the
      expression pattern of the mouse, chicken and pufferfish CRABP-I genes to
      substantiate this argument further. First we cloned and sequenced genes and
      promoter regions of the CRABP-I genes from chicken and the Japanese pufferfish,
      Fugu rubripes. Sequence comparison with the mouse gene did not show any large
      blocks of homology in the promoter regions. Nevertheless, the promoter of the
      chicken gene directed expression to a subset of the tissues that show expression
      with the promoter from the mouse gene. The pattern observed with the pufferfish
      promoter is even more restricted, essentially to rhombomere 4 only, indicating
      that this region may be functionally the most important for CRABP-I expression in
      the developing embryo.

PMID- 9608737
TI  - Restricted beta-galactosidase expression of a hygromycin-lacZ gene targeted to
      the beta-actin locus and embryonic lethality of beta-actin mutant mice.
AB  - beta-actin is a cytoskeletal protein that is ubiquitously expressed. To exploit
      the regulation the beta-actin gene, a promoterless hygromycin-lacZ fusion gene
      with a splice acceptor was introduced into the first intron of the beta-actin
      locus by homologous recombination in mouse embryonic stem (ES) cells. The
      targeted ES cells were hygromycin resistant and expressed beta-galactosidase
      (beta-gal) activity. However, no beta-gal activity was detected in heterozygous
      embryos. In adult heterozygotes, beta-gal activity was detected only in testes.
      RT-PCR analysis demonstrated the presence of both beta-actin exon 1-hygromycin-
      and exon l-exon 2-containing transcripts in homozygous mutant embryos. LacZ
      containing transcripts were detected in adult heterozygous tests and,
      surprisingly, in homozygous mutant embryos. These results demonstrate that the
      integration of the hygromycin-lacZ gene into the first intron of the beta-actin
      locus was not productive for the ubiquitous expression of beta-gal activity.
      Because this integration mimics certain types of gene trap events, it suggests
      that caution should be used when interpreting beta-gal expression patterns in
      genetic screens using gene trap strategies. In addition, mice homozygous for the
      beta-actin mutation developed normally up to embryonic day 8.5 (E8.5) but became
      growth retarded at E9.5 and subsequently died. The RT-PCR data indicate that this
      targeted mutation is a hypomorphic allele of beta-actin.

PMID- 9608738
TI  - Maternally expressed PGK-Cre transgene as a tool for early and uniform activation
      of the Cre site-specific recombinase.
AB  - A transgenic mouse strain with early and uniform expression of the Cre site
      specific recombinase is described. In this strain, PGK-Crem, Cre is driven by the
      early acting PGK-1 promoter, but, probably due to cis effects at the integration
      site, the recombinase is under dominant maternal control. When Cre is transmitted
      by PGK-Crem females mated to males that carry a reporter transgene flanked by
      loxP sites, even offspring that do not inherit PGK-Cre delete the target gene. It
      follows that in the PGK-Crem female Cre activity commences in the diploid phase
      of oogenesis. In PGK-Crem crosses complete recombination was observed in all
      organs, including testis and ovary. We prepared a mouse stock that is homozygous
      for PGK-Crem and at the albino (c) locus. This strain will be useful for the
      early and uniform induction of ectopic and dominant negative mutations, for the
      in vivo removal of selective elements from targeted mutations and in connection
      with the manipulation of targeted loci in 'knock in' and related technologies.

PMID- 9608739
TI  - The human pH aldolase A promoter directs widespread but muscle-predominant
      expression in transgenic mice.
AB  - In order to identify regulatory elements that direct widespread in vivo
      expression of a linked gene, we have examined one of the human aldolase A
      alternative promoters, the ubiquitous pH promoter, which is active in most foetal
      and adult tissues. We have used the pH promoter region to drive expression of an
      heterologous CAT reporter gene in transgenic mice. We show that a short 820 bp pH
      promoter fragment is able to confer a ubiquitous and reproducible activity
      pattern on the CAT reporter gene in most of the transgenic lines analysed, with a
      particularly high level of expression in adult skeletal muscle. Activity of this
      transgene was detected from early embryonic stages. Therefore, this pH promoter
      region appears to be a powerful tool to direct ubiquitous and early expression of
      a transgene in vivo. Deletion analysis revealed that: (i) the region between -651
      and -369 bp relative to the pH promoter transcription start site includes DNA
      elements capable of overriding effects of the surrounding chromatin at the
      integration site, (ii) the region between -285 and -211 bp is involved in pH
      promoter tissue-specific expression pattern in skeletal muscle and/or nervous
      tissues, (iii) the region located between -211 and -108 bp is necessary for its
      ubiquitous and muscle-predominant activity and (iv) the most proximal region
      downstream from -108 bp is still sufficient to confer an activity in brain and
      lung.

PMID- 9608740
TI  - Identification of transgenic mice by direct PCR analysis of lysates of epithelial
      cells obtained from the inner surface of the rectum.
AB  - Conventional screening protocols for transgene integration in mice employ tail
      tips or blood samples as sources to obtain genomic DNA preparations. We have
      developed a simple alternative non-surgical method. Epithelial cells are scraped
      off the inner surface of the rectum with a sterile plastic inoculation loop and
      are lysed with Kawasaki buffer. The lysate can be directly examined in a
      polymerase chain reaction (PCR) analysis without any need for further DNA
      purification. This procedure causes minimal harm and stress to the animals and
      repeated samples can be obtained as often as necessary. This technique has been
      used successfully to identify transgenic mice from a number of different lines.
      The method allows quick screening of numerous animals and contributes to a
      reduction of the number of surgical biopsies required.

PMID- 9608741
TI  - Rapid confirmation of gene targeting in embryonic stem cells using two long-range
      PCR techniques.
AB  - Gene targeting in mouse embryonic stem (ES) cells generally includes the analysis
      of numerous colonies to identify a few with mutations resulting from homologous
      recombination with a targeting vector. Thus, simple and efficient screening
      methods are needed to identify targeted clones. Optimal screening approaches
      require probes from outside of the region included in the targeting vector to
      avoid detection of the more common random insertions. However, the use of large
      genomic fragments in targeting vectors can limit the availability of cloned DNA,
      thus necessitating a strategy to obtain unique flanking sequences. We describe a
      rapid method to identify sequences adjacent to cloned DNA using long-range
      polymerase chain reaction (PCR) amplification from a genomic DNA library,
      followed by direct nucleotide sequencing of the amplified fragment. We have used
      this technique in two independent gene targeting experiments to obtain genomic
      DNA sequences flanking the mouse cholecystokinin (CCK) and gastrin genes. The
      sequences were then used to design primers to characterize ES cell lines with CCK
      or gastrin targeted gene mutations, employing a second long-range PCR approach.
      Our results show that these two long-range PCR methods are generally useful to
      rapidly and accurately characterize allele structures in ES cells.

PMID- 9608742
TI  - Characterization of two pore-forming proteins isolated from the outer membrane of
      Synechococcus PCC 6301.
AB  - Two major proteins, A and B, were isolated and purified from outer membranes of
      the unicellular cyanobacterium Synechococcus PCC 6301 by gel filtration, anion
      exchange chromatography, and preparative SDS-PAGE. Protein A revealed a single
      channel conductance of 0.4 nanoSiemens (nS) in 1 M KCl, whereas preparations
      containing both proteins showed two different conductance maxima of 0.4 and 0.9
      nS, suggesting that B also forms pores. The apparent molecular mass of the two
      closely migrating proteins was determined as 52 kDa, whereas native porin
      extracts revealed a relative molecular mass of ca. 140 kDa, indicating trimeric
      pore-forming units. Partial sequences of both proteins were obtained by N
      terminal sequencing of tryptic peptides, and the C-terminal amino acid sequences
      were derived from the complete proteins. These sequences were aligned to protein
      sequences available in the databases. The results are discussed.

PMID- 9608743
TI  - Identification and isolation of the indole-3-pyruvate decarboxylase gene from
      Azospirillum brasilense Sp7: sequencing and functional analysis of the gene
      locus.
AB  - The root-associated bacterium Azospirillum brasilense Sp7 produces the growth
      stimulating phytohormone indole-3-acetic acid (= IAA) via the indole-3-pyruvate
      pathway. The DNA region containing ipdC, the structural gene for indole-3
      pyruvate decarboxylase, was identified in a cosmid gene library of strain Sp7 by
      hybridization and has been sequenced. Upstream of the gene, two other ORF
      homologous to gltX and cysS were sequenced that are transcribed in the opposite
      direction. A functional analysis of the cloned ipdC region has been performed. To
      test the expression of the gene, a lacZ-Km cartridge was introduced into the
      gene. By this construct, tryptophan-dependent stimulation of gene expression in
      A. brasilense Sp7 was observed. Evidences for the existence of another copy of
      the ipdC gene in the Azospirillum genome are also reported.

PMID- 9608744
TI  - Identification of clinically important species of Enterococcus within 1 day with
      randomly amplified polymorphic DNA (RAPD).
AB  - The use of randomly amplified polymorphic DNA (RAPD) for rapid, reliable, and
      easily interpreted identification of enterococci was evaluated. Nineteen type
      strains of Enterococcus, 12 reference strains, and 114 clinical isolates of
      Enterococcus were analyzed. Discrimination was obtained between most type
      strains, the exceptions being Ent. casseliflavus and Ent. flavescens, which had
      relatively similar RAPD-profiles. Ent. faecalis and Ent. faecium were readily
      separated, and Ent. gallinarum and Ent. durans could also be identified. Extracts
      to be used in the polymerase chain reaction (PCR) were prepared directly from
      agar plate colonies, which made it possible to complete the identification
      procedure in one day. RAPD was proved to be a fast and reliable method for
      identification of most Enterococcus spp. of clinical significance.

PMID- 9608745
TI  - The effect of the lacY gene on the induction of IPTG inducible promoters, studied
      in Escherichia coli and Pseudomonas fluorescens.
AB  - The role of the Escherichia coli lacY gene product (the lactose permease) in the
      induction of isopropyl-beta-D-thiogalactopyranoside (IPTG) inducible promoters
      was studied in E. coli and P. fluorescens. This was done by comparing strains
      containing a lacIPOZYA chromosomal insert with newly constructed strains
      containing inserts without the lacY gene (lacIPOZ). The lactose operon inserts
      were introduced as single-copy chromosomal inserts to eliminate differences in
      expression caused by differences in copy number. Comparison between the two types
      of inserts showed that the lactose permease was essential to allow growth on
      lactose by both bacteria and that the lactose permease plays an important role in
      transporting the inducer IPTG across the membrane of P. fluorescens. The use of a
      functional lactose permease allows expression of beta-galactosidase to increase
      more than fivefold from a wild-type lac promoter in P. fluorescens SS1001. We
      suggest that an increase in the rate of protein synthesis from lac-type promoters
      could be enhanced if an active lactose permease is present as well.

PMID- 9608746
TI  - Effects of chlorhexidine diacetate on ruminal microorganisms.
AB  - The objectives of this study were to examine the effects of chlorhexidine
      diacetate on growth and L-lactate production by Streptococcus bovis JB1 as well
      as the effects of this antimicrobial compound on the mixed ruminal microorganism
      fermentation. Addition of 1.8 microM chlorhexidine diacetate to glucose medium
      resulted in a lag in growth by S. bovis JB1, and growth was completely inhibited
      in the presence of 3.6, 9.0, and 18 microM chlorhexidine. When 6.2 microM
      chlorhexidine diacetate was added to glucose medium after 2 h of incubation,
      glucose utilization and L-lactate production by S. bovis JB1 were reduced.
      Phosphoenolpyruvate-dependent phosphorylation of 14C-glucose by toluene-treated
      cells of S. bovis JB1 was inhibited by increasing concentrations (1.8 to 18
      microM) of chlorhexidine, whereas only the 18 microM concentration reduced the
      membrane potential (delta psi). Chlorhexidine diacetate was a potent inhibitor of
      L-lactate and methane production from glucose fermentation by mixed ruminal
      microorganisms. However, because chlorhexidine also decreased acetate and
      propionate concentrations and increased ammonia concentrations in mixed-culture
      incubations, this antimicrobial compound may have limited application as a
      ruminant feed additive.

PMID- 9608747
TI  - The characteristics of arylamine N-Acetyltransferase in Pseudomonas aeruginosa.
AB  - N-Acetyltransferase (NAT), responsible for bioactivation and detoxification of
      arylamines, has been demonstrated to be widely distributed in many organisms
      ranging from humans to microorganisms. Using high performance liquid
      chromatography (HPLC) to analyze NAT activity in bacteria, the authors found that
      Pseudomonas aeruginosa exhibited high NAT activity with 2-aminofluorene (2-AF) as
      substrate. Characteristics of this bacterial NAT were further investigated. The N
      acetylation catalyzed by this enzyme is an acetyl coenzyme A (AcCoA)-dependent
      reaction. As the concentration of AcCoA in the reaction mixture was increased,
      the apparent K(m) and Vmax for 2-AF increased. The K(m) and Vmax were 0.504 +/-
      0.056 mM and 31.92 +/- 3.23 nmol/min/mg protein, respectively, for the
      acetylation of 2-AF with 0.5 mM AcCoA. The optimum pH for the enzyme activity was
      estimated to be around 8.5. It was active at a temperature range from 5 degrees C
      to 55 degrees C, with maximum activity at 37 degrees C. The enzyme activity was
      inhibited by divalent metal ions including Cu++, Fe++, Zn++, Ca++, Co++, Mn++,
      and Mg++, suggesting that a sulfhydryl group is involved in the N-acetylation
      activity. The three chemical modification agents, iodoacetamide, phenylglyoxal,
      and diethylpyrocarbonate, all exhibited a dose-, time-, and temperature-dependent
      inhibition effect. Preincubation of the NAT with AcCoA provided significant
      protection against the inhibition of iodoacetamide and diethylpyrocarbonate, but
      only partial protection against the inhibition of phenylglyoxal. These results
      indicate that cysteine, histidine, and arginine residues are essential for this
      bacterial enzyme activity, and the first two are likely to reside on the AcCoA
      binding site, but arginine residue may be located only near the AcCoA binding
      site. Our data demonstrate that P. aeruginosa possesses highly active N
      acetyltransferase which shares a similar catalytic mechanism as that of higher
      organisms. These findings are very helpful for further investigating the role of
      arylamine NAT in this bacterial species.

PMID- 9608748
TI  - Determination of host specificity of cowpea miscellany Rhizobium spp. by nodABC
      lacZ fusion.
AB  - Cowpea miscellany group of rhizobia are generally broad host range.
      Transconjugants of these cowpea rhizobial isolates having nodABC-lacZ fusion were
      monitored for flavonoid/root exudate-induced activation of the nod genes in terms
      of beta-galactosidase activity, thus determining the potential host range of the
      rhizobial isolates.

PMID- 9608750
TI  - High-level expression of ice nuclei in Erwinia herbicola is induced by phosphate
      starvation and low temperature.
AB  - In laboratory cultures of ice nucleation-active (Ice+) Erwinia herbicola
      isolates, it has been difficult to achieve high-level expression of ice nuclei,
      especially nuclei active at temperatures warmer than -5 degrees C (i.e., type 1
      ice nuclei). Here we demonstrate that starvation for phosphate and exposure to
      low temperature triggers expression of ice nuclei in E. herbicola cultures.
      Starvation for nitrogen, sulfur, or iron was less effective. Under optimal
      conditions with two different strains, essentially all cells produced ice nuclei
      active at -10 degrees C or warmer, with an average of 22% containing type 1 ice
      nuclei within 1 h of a low-temperature shift. These conditions did not greatly
      enhance the shedding of ice nucleation-active membrane vesicles that are known to
      be produced by Ice+ E. herbicola isolates. These results support the theory that
      the Ice+ phenotype may allow nutrient-limited epiphytes to trigger freezing
      damage, releasing nutrients from host plants.

PMID- 9608749
TI  - Lysogeny of Oenococcus oeni (syn. Leuconostoc oenos) and study of their induced
      bacteriophages.
AB  - A large number of strains of Oenococcus oeni (formerly Leuconostoc oenos) that
      had been isolated from wines were checked for lysogeny with mitomycin C as
      inducer. As a result of this test, 45% of the strains proved to be lysogenic,
      suggesting that lysogeny is widespread among bacteria isolated from wines during
      malolactic fermentation. The sensitivity of bacteria to phages was very
      different, depending on the strain. All the lysogenic strains were resistant to
      infection by the temperate phage they released. Some phages infected none of the
      strains. Phages of Oenoc. oeni had a classical morphology, an isometric head, and
      a long striated tail. With the broadest host strain as an indicator, phages were
      detected in wines after malolactic fermentation.

PMID- 9608751
TI  - Nucleic acid and protein elimination during the sugar manufacturing process of
      conventional and transgenic sugar beets.
AB  - The fate of cellular DNA during the standard purification steps of the sugar
      manufacturing process from conventional and transgenic sugar beets was
      determined. Indigenous nucleases of sugar beet cells were found to be active
      during the first extraction step (raw juice production) which was carried out at
      70 degrees C. This and the consecutive steps of the manufacturing process were
      validated in terms of DNA degradation by competitive PCR of added external DNA.
      Each step of the process proved to be very efficient in the removal of nucleic
      acids. Taken together, the purification steps have the potential to reduce the
      amount of DNA by a factor of > 10(14), exceeding by far the total amount of DNA
      present in sugar beets. Furthermore, the gene products of the transgenes neomycin
      phosphotransferase and BNYVV (rhizomania virus) coat protein CP21 were shown to
      be removed during the purification steps, so that they could not be detected in
      the resulting white sugar. Thus, sugar obtained from conventional and transgenic
      beets is indistinguishable or substantially equivalent with respect to purity.

PMID- 9608752
TI  - Recombinant flounder growth hormone from Escherichia coli: overexpression,
      efficient recovery, and growth-promoting effect on juvenile flounder by oral
      administration.
AB  - An efficient production method for recombinant flounder growth hormone (r-fGH)
      from Escherichia coli was developed and the biological activity of purified r-fGH
      was examined using juvenile flounder. The use of bicistronic construction in the
      expression plasmid resulted in the production of over 40% of the E. coli cellular
      protein as r-fGH. The r-fGH was recovered from cell lysates following inclusion
      body washing, solubilization and refolding in sodium dodecylsulfate (SDS)
      solution, and removal of contaminated proteins with secondary butanol treatment.
      The SDS content in purified r-fGH solution was adjusted to appropriate levels by
      diafiltration. More than 47% of the r-fGH was recovered from the E. coli cell
      lysates and the purity of recovered r-fGH was 98%. The oral administration of
      purified r-fGH to juvenile flounder, once a week for 4 weeks at a dosage of 40
      micrograms r-fGH g-1 fish body weight, resulted in significant increases both in
      weight and length. These results of overexpression, simple purification with high
      recovery yield and purity, and good growth-promoting activity of the r-fGH
      suggest that the production scheme described in this study is useful for the
      potential application of r-fGH in fish farming.

PMID- 9608753
TI  - [MacDonald Critchley (February 2, 1900-October 15, 1997)].

PMID- 9608754
TI  - New and old treatments for multiple sclerosis.

PMID- 9608755
TI  - [Treatment of Guillain-barre syndrome: immunoglobulins or plasmapheresis?].
AB  - The aim of this study was to compare the efficacy of IgIV versus plasmapheresis
      in the treatment of Guillain-Barre syndrome. Twenty-four Guillain-Barre patients
      were treated either with IgIV (n = 17), or plasmapheresis (n = 7). Evolution
      during the first year after onset were assessed using the motor functional scale
      of Hughes and nerve conduction studies. IgIV treated patients had better
      functional recovery than the plasmapheresis group (p < 0.05) and shorter hospital
      stays (p < 0.05). These differences were significant from day 30 after treatment.
      Complications occurred in 14 patients: 9 (58%) in the IgIV group, and 5 (71%) in
      the patients treated with plasmapheresis. IgIV treated patients had better
      functional recovery scores and shorter hospital stays. There were no differences
      in the complication rates. Therefore we believe that IgIV is the treatment of
      choice for Guillain-Barre syndrome in our clinical setting.

PMID- 9608756
TI  - [Lymphocytic meningitis in a 45-year-old male].

PMID- 9608757
TI  - [Spontaneous bilateral tectal hemorrhage].

PMID- 9608758
TI  - [Seven hundred words and expressions of misleading translation in neurology,
      neuropsychiatry and neurosurgery].

PMID- 9608759
TI  - [Intracranial hemorrhage with fluid level. A case report without coagulation
      alterations].
AB  - The presence of intracranial hemorrhage with a fluid-blood level in patients
      receiving anticoagulant medication or with coagulopathy is an infrequent but well
      documented complication. We reported a patient with a fluid-blood level with
      normal haemostasis. A 62-year-old-man was admitted with a left putaminal
      hemorrhage containing a fluid-blood level, but without abnormal haemostasis. Five
      months later the patient returned to the hospital because of a transient ischemic
      attack. A cranial CT demonstrated a hypodensity in the left putamen nucleus and
      corona radiata. Electrocardiogram revealed atrial fibrillation and a cardiac
      ultrasonographic examination showed mitral annulus calcification and left atrial
      enlargement. The finding of intracranial fluid-blood level has been seen in
      patients with arteriovenous malformations, primary and metastatic neoplasm,
      radiation-induced necroses, cerebral amyloid angiopathy, intrainfarct hematoma
      and without any identified aetiology. We suggest that in our patient this
      disorder was due to a intrainfarct hematoma.

PMID- 9608760
TI  - [Mitochondrial respiratory chain deficiency may present as multiple sclerosis].
AB  - Defects of the mitochondrial respiratory chain are associated with a great
      variety of clinical disorders. In addition to the well recognized syndromes, a
      significant number of patients present non-specific encephalopathic disorders. In
      consequence these types of mitochondrial disorder are very difficult to diagnose
      on clinical features alone. In this paper, we describe the clinical and the
      magnetic resonance findings of 2 patients with a neurological syndrome
      indistinguishable from multiple sclerosis (Poser). Muscle biochemistry revealed
      defect of complex IV of the respiratory chain. We think that these patients have
      a mitochondrial encephalomyopathy. We suggest that in patients presenting as
      atypical multiple sclerosis it could be necessary investigating mitocondrial
      encephalopathy.

PMID- 9608761
TI  - ["Telegraphist's " stroke].

PMID- 9608762
TI  - Acute hemichorea caused by a cavernous angioma in the caudate.

PMID- 9608763
TI  - [Dopamine receptors and dyskinesias].

PMID- 9608764
TI  - [Advances in anesthesiology in the 90's].
AB  - Author looks over the novelties in anaesthesiology in the 90-ies; (1) effort to
      relief not only the postoperative, but in general, every kind of pain; (2)
      publication of evidence based guidelines; (3) standpoints according to
      perioperative risk factors; (4) conception of preemptive analgesia; (5) usage of
      modern brain imaging techniques in anaesthesiology also; (6) researches about the
      sites, where general anaesthetics exert their effect; (7) new volatile
      anaesthetics (desflurane, sevoflurane); (8) researches, targeting the use of
      xenon; (9) new i.v. anaesthetics-analgesics (propofol, remifentanil, S(+)
      ketamine, eltanolone) and their administration (TCI); (10) potential interactions
      between NO and anaesthetic agents; (11) new neuromuscular blocking drugs
      (mivacurium, rocuronium, cis-atracurium) and the new possibilities of
      neuromuscular monitoring; (12) question of difficult intubation (McCoy and
      bullard laringoscopes, laryngeal mask); (13) synthesis of the new elements for
      the challenges of the surgical practice: the anaesthesiological solution of
      laparoscopic surgery, one-day surgery, minimally invasive heart-surgery; (14)
      TIVA (recognition of awareness during operation); (15) closed circuit
      anaesthesia; (16) reduction of expenses; (17) application of computer and data
      management techniques; (18) organizational steps in order to achieve an
      integrated standard throughout the country.

PMID- 9608765
TI  - [Combined therapy of metastatic liver neoplasms: intrahepatic chemoembolization
      and systemic chemotherapy].
AB  - Chemoembolisation has been an effective treatment-option for unresectable
      colorectal liver metastases, however it frequently fails because of tumour
      progression outside the liver. We conducted a pilot study to assess the toxicity
      and efficacy of combined regional and systemic chemotherapy for patients having
      liver dominant disease. Three cycles of chemoembolisation using 50 mg adriamycin,
      8 mg mitomycin C, 50 mg cisplatinum admixed with 10 ml of lipiodol were given at
      6 weeks intervals. The systemic therapy consisted of 425 mg/m2 5-fluorouracil and
      20 mg/m2 leucovorin by intravenous infusion 1-5 days repeated every 28 days. 41
      patients were treated for the period 1st January 1994-31st December 1996. Out of
      these 27 were male, 14 female with a medium age of 62 years (40-78). Primary site
      of tumour was colon in 30 cases and rectum in 11 cases. 14 patients received
      prior chemotherapy (5 adjuvant, 9 palliative). Mean follow up time is 18 months
      (4-36) in this study. 27 partial and 1 complete remissions were achieved at the
      average response rate of 68%. Mean time of progression was 10.7 months (4-18),
      overall survival time was 15 months (4-36). Common toxicity was the
      postembolisation syndrome consisting of abdominal pain, fever, chills, reversible
      elevated liver enzymes. Four patients had drug-induced cholangiohepatitis. At 15
      patients we experienced grade 3, toxicity (5 diarrhoea, 3 mucositis, 2 vomiting,
      2 leukopenia, 2 thrombocytopenia, one skin rush). No treatment related death or
      catheter complications were observed. Although these treatment results are
      superior to our historical experience, a controlled clinical trial will be
      acquired to establish this approach.

PMID- 9608766
TI  - [Body composition in overweight children, healthy children as well as children
      with mucoviscidosis, measured by multifrequency impedance].
AB  - The body composition of a total of 90 children (aged 5-18) were subjected to
      multifrequency impedance measurement with a Human IM Scan impedance analyser. We
      compared data of 30 overweight children (17 boys, 13 girls; mean age 11.47 yrs,
      range: 4-17 yrs), 30 children with cystic fibrosis (12 boys, 18 girls; mean age
      12.8 yrs, range: 3-24 yrs) and 30 healthy children (12 boys, 18 girls; mean age
      13.4 yrs, range 7-18 yrs). The percentage of fat mass was found to be inversely
      proportional to total body water. Extracellular water expressed as a percentage
      of the total body water was significantly higher in overweight children than in
      the other two groups: (p < 0.01) between children with cystic fibrosis and
      overweight children, (p < 0.05) between healthy children and overweight children.
      Extracellular water expressed as a percentage of total body water was lower in
      children with cystic fibrosis than in healthy children (p < 0.05). The ratios of
      extracellular mass and body cell mass to body weight were significantly lower in
      overweight children than in healthy children (p < 0.01) or in children with
      cystic fibrosis (p < 0.01). The ratio of exchangeable sodium and potassium was
      lower in all three groups than the normal value given for adults (> 0.87), but in
      overweight children it was significantly higher than in the other two groups; (p
      < 0.01) between children with cystic fibrosis and overweight children, (p < 0.05)
      between healthy children and overweight children. Multifrequency impedance
      measurement is reliable, fast, non-invasive, easy to carry out, therefore we
      consider it very useful in determining the body composition of children in
      various pathological conditions.

PMID- 9608768
TI  - [Biometric bases: basic concepts of probability calculation].
AB  - The author gives or outline of the basic concepts of probability theory. The
      bases of the event algebra, definition of the probability, the classical
      probability model and the random variable are presented.

PMID- 9608767
TI  - [Iron deficiency anemia caused by an arteriovenous malformation in the distal
      ileum].
AB  - The case of a young woman with chronic iron deficiency anemia is described. Her
      consequent guaiac-positive stool suggested a gastrointestinal bleeding behind her
      anemia. The use of the conventional diagnostic techniques did not result in a
      definitive diagnosis. The source of the hemorrhage was later detected by the aid
      of selective mesenteric arteriography as an unusual form of arteriovenous
      malformations localized to the small intestine. 20 months passed since the
      resection of the affected intestinal segment. During this period of close follow
      up no clinical signs of recurrent gastrointestinal hemorrhage was observed. The
      authors briefly review the relevant literature.

PMID- 9608769
TI  - [Prognostic factors in breast cancer].
AB  - Prognostic factors are clinical and pathological features that give information
      in estimating the likely clinical outcome of an individual suffering from cancer.
      The author gives a short review of the most important prognostic factors in
      breast cancer. 376 breast cancer cases of a ten year interval in a county
      hospital are summarized. Traditional clinico-pathological parameters i.e. TNM and
      steroid receptor status are discussed. The more common karyotipic, oncogene and
      tumor suppressor gene alterations are outlined in the study. Methods for their
      detection are presented and their value in prognostication is reviewed. Emphasis
      was laid on steroid receptors, c-erpB-2, p53 and bcl-2 alterations. Genes
      responsible for heritable forms of increased breast cancer risk are briefly
      reviewed.

PMID- 9608770
TI  - [Drug therapy of gastroesophageal reflux (a prospective controlled clinical
      trial)].
AB  - One year follow up(1.5, 3, 6, 12 months) study was established to examine the
      role of several classes of drugs in the treatment of reflux disease in 40
      patients on the basis of objective control parameters (pH-metry, endoscopy,
      histology). The therapy was initiated, respectively, the different stage of
      severity (Savary-Miller): in stage 0 sucralfate + domperidone, in stage I and II:
      ranitidine + domperidone and in stage III-IV omeprazole was introduced. Our
      results proved that sucralfate + domperidone is curative on reflux oesophagitis
      in stage 0 cases. In stage I sucralfate and domperidone were effective in 3 of 9
      cases, ranitidine + domperidone was optimal in 5 of 9, and omeprazole was
      required in 1 of 9 patients. In stage II, ranitidine + domperidone was effective
      only in 4 of 11 patients, and the initial therapy was modified to omeprazole in 7
      of 11 patients to find the optimal drug in this stage. In stage III and IV only
      omeprazole showed curative effect and the doses required were 20 mg in 8 of 13
      and 40 mg in 5 of 13 patients. The complaints improved in 34 of 40 patients after
      6 weeks treatment, while histological healing of reflux oesophagitis was observed
      in 12 of 40 cases. After 3 months the endoscopic healing rate was 28/40, but
      histological healing could be reached after 6 months of optimal treatment in 30
      of 40 cases. We can conclude, that the optimal drug selection may result a rapid
      improvement of complaints, but endoscopic and histological regeneration of the
      oesophageal mucosa is more graduated with time. The healing process of the reflux
      oesophagitis requires 3 months. Proton pump inhibitor drugs have an enhanced role
      in the treatment of gastrooesophageal reflux disease, and our results proved that
      the efficient and safety treatment of mild form (stage II) of disease requires
      the administration of proton pump inhibitors.

PMID- 9608771
TI  - [Mutation analysis in the CTG-base multiplication in a family with myotonic
      dystrophy in three generations].
AB  - A PCR-based method with a novel silver staining detection was developed for the
      determination of CTG repeat number in the 3' untranslated region of the MD-PK
      gene responsible for myotonic dystrophy. Through the investigation of a family
      with affected members in three generations the application of the method is
      presented. According to the results, healthy individuals were verified easily,
      and the repeat number in patients with mild features or with premutation could be
      determined accurately. In severe clinical forms, e.g. congenital myopathy, the
      expansion can be deduced only from the lack of amplification, however, this is
      also helpful if the segregation of familial alleles is known.

PMID- 9608772
TI  - [Fetal atrioventricular septal defect associated with Patau and Edwards
      syndromes, as well as trisomy 22].
AB  - The atrioventricular septal defect is usually associated with trisomy 21 and it
      may be observed in the heterotaxia syndromes. Atrioventricular septal defect may
      be associated with 8p deletion. There are reported cases of familial
      atrioventricular septal defect. Atrioventicular septal defect is rarely
      associated with other chromosomal abnormalities. We are reporting three unusual
      cases of atrioventricular septal defect that were associated with trisomy 13, 18
      and 22. This association may be due to effect of genetic loci on the 13, 18 and
      22 chromosome which could play the role in the development and fusion of
      endocardial cushion and atrioventricular septal defect.

PMID- 9608773
TI  - [A case of spontaneous rupture of a cervical hematoma causing respiratory
      insufficiency].
AB  - The authors review a case of a patient with spontaneous cervical hematoma without
      trauma. The similar cases of the international literature, the causes (local and
      systemic vascular disorders, inflammatory and neoplastic disease of the
      surrounding tissues) are summarized and the importance of the computerized
      tomography in connection with the described case is emphasized.

PMID- 9608774
TI  - [Remembering Janos Balassa].

PMID- 9608775
TI  - [Pathography of J. F. Kennedy].

PMID- 9608776
TI  - [Quo vadis "suprema lex"?].

PMID- 9608777
TI  - [An evaluation of the XVI International Congress of Clinical Allergy and
      Immunology].

PMID- 9608778
TI  - [Eosinophils in peripheral blood and nasal mucus, in asthmatic and healthy
      subjects].
AB  - MATERIAL AND METHODS: 600 subjects were studied, chosen at random, between 1 and
      55 years old, 300 asthmatic and the rest apparently healthy. RESULTS: Of 300
      asthmatic patients, the average concentration of eosinophils in peripheral blood
      was of 615.93/mm3 (p = 0.000004, R = 2.13), the asthmatic patients with levels of
      eosinophils over a 400/mm3 presented: more severe asthma per month and made use
      of hospital services more often, (p = 0.00001, R = 3.56). In 195 patients were
      detected eosinophils in nasal mucus with an average concentration of 10.54% (p =
      0.04, R = 0.70). CONCLUSIONS: The incidence and prevalence of asthma seem favored
      by the lact of predictive sensors. In the study, the blood and nasal eosinophils,
      in high levels were identified in subjects at high risk, consequently its use is
      proposed to diagnose and follow up, with the goal of applying measures in the
      balanced phase of the health-illness chain.

PMID- 9608779
TI  - [Prevalence on acute asthma in children].
AB  - OBJECTIVE: In this descriptive study we considered age, sex, and admission's
      month of children under 15 years-old admitted to the emergency room for acute
      asthma between January 94 to july 95. MATERIAL AND METHOD: There were 594 boys
      and 421 girls. Male to female mean ratio was 1.4:1. We found a greater and
      significative admission's number in boys than in girls (x2: p < 0.001). Odds
      ratio was greater in boys. 1.18 (CI 95%: 1.04-1.35) than in girls, 0.85 (CI 95%:
      0.750.96). RESULTS: The acute asthma admissions monthly trend was in third place
      (median) and second place (mode) when compared with other children's admission
      diagnoses. Total monthly admissions amount did not show a significative
      differences when compared the first seven months of 1994 and 1995 (Mann-Whitney's
      U: p > 0.05). CONCLUSIONS: The acute asthma admissions are currently predominant
      in boys over girls, and that bronchial asthma is one of the more frequent
      emergency admission's causes in children.

PMID- 9608780
TI  - [Comparative study of secretory IgA].
AB  - OBJECTIVE: The aim of this study was measure and compare Secretory IgA levels in
      the respiratory tract. DESIGN: Cross-sectional study. SETTING: Neumology
      Department of General Hospital. La Raza Medical Center Mexico. MATERIAL AND
      METHOD: There were 35 volunteers. Samples of sputum, washings nasopharyngeal and
      bronchial was obtained from thirty five patients with COPD. Measurement of SIgA
      levels was performed by nephelometric technique. Results is reported as ratio of
      SIgA concentration/Total proteins concentration named SIgA relative
      concentration. Correlation index was obtained of three type of samples. RESULTS:
      The SIgA values of sputum, washings nasopharyngeal and bronchial was similar
      similar +/- 0.011, 0.064 +/- 0.007 and 0.082 +/- 0.017 respectively). Multiple
      correlation was r = 0.508 (p < 0.01).

PMID- 9608781
TI  - [Asthma associated with gastroesophageal reflux].
AB  - OBJECTIVE: In order to explore the association between poorly controllable asthma
      and gastroesophageal reflux (GER), a prospective clinical trial is presented.
      MATERIAL AND METHOD: This trial included 28 patients with negative atopic
      indicators who presented difficulty in the management of their disease. All
      patients underwent a complete medical history as well as skin tests for common
      airborne allergens, total serum IgE, peripheral blood eosinophils, spirometry,
      chest X-ray and esophageal barium films. Additionally, esophageal endoscopy was
      performed on 9 patients, and esophageal manometry in 1 patient. All were
      submitted to antireflux therapy and received omeprazole and cisapride for 8
      weeks. RESULTS: Complete improvement was observed in 24 patients (85.7%),
      moderate improvement in 3 patients (10.7%), and no improvement in 1 patient
      (3.6%). Three patients required antireflux surgery. CONCLUSIONS: Symptoms
      reappeared 2-3 weeks after suspending treatment, which led to the recommendation
      that antireflux measures become a way of life for these patients.

PMID- 9608782
TI  - [Morphological features of the nasal mucosa in healthy children exposed to
      different concentrations of atmospheric pollution].
AB  - OBJECTIVE: During the last decades the impact of pollution in big cities on the
      upper respiratory tract of children has become an issue of interest. The purpose
      of the present study was to determine if exposure of healthy children to
      different concentrations of atmospheric pollution alters morphologically the
      nasal respiratory epithelium. MATERIAL AND METHODS: In this randomised,
      prospective, open clinical trial we included 71 healthy children matched for age
      and sex and divided them into 3 groups: Group I, 31 children from Mexico City.
      Group II, 21 children from Tula, Hidalgo a moderate polluted area, and Group III,
      19 children from Contepec, Michoacan, a rural non-polluted area. We took a nasal
      biopsy from the lower turbinate and performed nasal cytology in all children. The
      samples were examined twice by a pathologist with a double-blind technique. Ozone
      measurements were taken during 1992. RESULTS: Nasal symptoms (nasal obstruction,
      pruritus and dryness) were present in 96.8%, 71.4% and 52.6% of patients in
      groups I, II and III respectively (p = 0.001). We also found bilateral
      hypertrophy turbinates in 100% of children in group I versus 81% and 73% in
      groups II and III (p = 0.009). Citologic examination disclosed no significant
      differences among the study groups, although p values were 0.06 respecting
      inflammation and abnormal goblet cells when we compared group I versus group II
      and III. Respecting histological examination we found significant differences
      when comparing group I versus II and III in squamous metaplasia (p = 0.02) and
      pseudoepitheliomatous hyperplasia (p = 0.003), with not significant differences
      among keratinization (p = 0.06) and dysplasia (p = 0.06). CONCLUSIONS: The
      results of this study indicate that exposure to a polluted atmosphere is followed
      by severe changes in the histology and cytology of the nasal mucosa in healthy
      children, with these changes being more frequent and severe in the more polluted
      areas. These findings implicate that we must put more attention on the long term
      effects of atmospheric pollution in order to establish stronger control measures.

PMID- 9608783
TI  - Higher prevalence of diabetes in hypertensive subjects with upper body fat
      distribution.
AB  - OBJECTIVE: To analyze the association of hypertension and upper body fat
      distribution on the occurrence of non-insulin-dependent diabetes mellitus in
      Mexicans. MATERIAL AND METHODS: It was a population-based cross-sectional study
      in Cuajimalpa, a district of Mexico City. A total of 1066 subjects were home
      interviewed, and attended our clinic for fasting plasma glucose sampling, blood
      pressure and anthropometric measurements. Diabetes was defined according to the
      World Health Organization criteria, and hypertension as a blood pressure equal to
      or greater than 140/90. The ratio of upper to lower body skinfolds was used to
      estimate body fat distribution. RESULTS: The prevalence of diabetes was 12.0%.
      There was a significant positive trend in the age and sex adjusted prevalence of
      diabetes according to the magnitude of hypertension (p = 0.0006) and upper body
      fat distribution (p = 0.007). The age and sex adjusted prevalence in normotensive
      subjects with lower body fat distribution was 7.1% (95% confidence interval 5.9
      8.2) whereas it was 19.9% (CI 17.0-22.8) in those with hypertension and upper
      body fat distribution. The prevalence of diabetes in Mexicans was high and it may
      be related to a genetic susceptibility for an insulin resistance syndrome.
      CONCLUSIONS: These results indicate that there is a dose response effect in the
      association of hypertension and upper body fat distribution with diabetes in
      Mexicans, and that there may be an interaction in the effect of hypertension and
      body fat distribution in this syndrome.

PMID- 9608784
TI  - [Case-control study of an outbreak of S. marcescens in a neonatal intensive care
      unit].
AB  - OBJECTIVE: To analyze an outbreak of Serratia marcescens in a neonatal intensive
      care unit and identify the risk factors associated to the development of
      infection. MATERIAL AND METHODS: It was a case-control study from March to July
      1995. Factors included were age, sex, intravascular devices, nebulizers,
      mechanical ventilation, use of total parenteral nutrition (TPN), underlying
      diseases, surgical interventions, tubes, previous antimicrobial treatment and
      days of exposure. The associations were explored using the odds ratio. RESULTS:
      24 cases and 30 controls were included. In the univariate analysis the
      significant risk factors (OR,IC) were use of central venous catheter (4.57, 1.01
      23.5), days of use of TPN (4.38, 1.03-16.5), days of previous antimicrobial
      treatment (4.87, 1.60-22) and days of exposure (2.7, 2.65-27.6). In the
      multivariate analysis the significant risk factors were previous antimicrobial
      treatment (3.98, 2.36-18.2), days of previous antimicrobial treatment (6.76, 3.02
      24.6) and days of use of TPN (4.87, 1.67-15.6). CONCLUSIONS: The significant risk
      factors in our study were previous antimicrobial treatment, days of antimicrobial
      and days of use of TPN.

PMID- 9608785
TI  - [Antibiotic resistance of Helicobacter pylori in an infectious disease referral
      center].
AB  - OBJECTIVE: To estimate the frequency of H. pylori clinical isolates resistant to
      six commonly used antimicrobials. DESIGN: Cross-sectional observational study.
      SETTING: A tertiary-referral health care institution in Mexico City.
      PARTICIPANTS: 31 isolates of H. pylori from 31 patients with chronic antral
      gastritis were obtained from gastric mucosal biopsy specimens. MAIN OUTCOME
      MEASURE: The Minimum Inhibitory Concentration (MIC) to ampicillin, amoxycillin,
      tetracycline, doxycycline, metronidazole and to colloidal bismuth subcitrate was
      determined by the agar plate dilution test. RESULTS: All isolates showed to be
      susceptible to the former four antibiotics but only in 46% and 55% growth was
      inhibited by 8 micrograms/mL and 16 micrograms/mL of metronidazole, respectively.
      All isolates were inhibited by < or = 128 micrograms/mL of bismuth. A 50%
      increase in the percentage of metronidazole-resistant isolates (MIC > or = 8
      micrograms/mL) between 1988 to 1992 was observed. CONCLUSION: There is a need of
      future studies in our setting aimed at assessing the cost/effectiveness of
      diverse H. pylori-associated peptic ulcer treatment options.

PMID- 9608786
TI  - [Prognostic factors in breast cancer with contralateral supraclavicular or
      axillary lymphatic metastases].
AB  - OBJECTIVE: To evaluate prognostic factor differences between surviving and
      decreased breast cancer patients in clinical stage IV with supraclavicular or
      contralateral axilla metastasis when first seen. METHODS: From the clinical
      records of 13 years (1975-88) two groups of ten patients each were obtained.
      Group 1 were women alive and free of disease for more than five years. Group 2
      had similar characteristics but had died of the disease. In both groups clinical
      data were evaluated (age, menstrual status and survival); from slides the
      histologic factors like tumor size, nodal status, fibrosis percentage,
      inflammatory infiltrate, nuclear grade and necrosis were evaluated;
      immunohistochemistry of CD34 for angiogenesis, cathepsin D, p53 antioncogen, c
      erb-B2 oncogen, epidermic growth factor, estrogen and progesterone receptors and
      cellular kinetics were performed; Kaplan Meier survival curves were constructed
      for the factors showing intergroup differences. RESULTS: The factors associated
      to the living patients were: low inflammatory infiltrate (p = 0.001), low
      fibrosis (p = 0.007), lower p53 expression (p = 0.03) and positive estrogen
      receptor (p = 0.03); other factors were marginally associated: positive
      progesterone receptor (p = 0.07) and having less than 6 positive lymph nodes (p =
      0.07).

PMID- 9608787
TI  - [Neonatal bacterial meningitis in a tertiary treatment center].
AB  - OBJECTIVE: To determine incidence, etiologic agents and clinical manifestations
      of bacterial meningitis in patients hospitalized in the newborn ward at the
      Hospital Infantil de Mexico in Mexico City and establish the incidence of
      meningitis in newborns admitted with respiratory distress syndrome (RDS) and
      determine how often blood cultures are negative in bacterial meningitis in this
      population. METHODS: Retrospective chart review of patients with bacterial
      meningitis admitted to our hospital. STUDY PERIOD: January 1990-July 1995.
      RESULTS: There were 959 admissions to the neonatal intensive care unit (NICU).
      The overall incidence of bacterial meningitis was 32.3/1000 admissions; however,
      among 170 patients with RDS, [corrected] meningitis was detected in one (5.9/1000
      RDS patients). Of the 31 patients with bacterial meningitis, 10 were preterm (PT)
      and 21 term (T). In the cerebrospinal fluid (CSF) isolates, there was a
      predominance of gram negative rods (n: 19; 61%). Clinical findings associated to
      meningitis were non-specific and there were no differences between PT and T
      infants. From 31 patients, 19 had negative blood cultures at the time of
      diagnosis (61%). Mortality associated to bacterial meningitis was [corrected] 40%
      and 23%, for PT and T, respectively (p = NS). CONCLUSIONS: The incidence of
      bacterial meningitis in the study population was high. Most isolates in CSF were
      gram-negative rods. Clinical findings in meningitis were non-specific and there
      were no differences between PT and T. Most of the patients (61%) had negative
      blood cultures at the time of diagnosis.

PMID- 9608788
TI  - [Gastrointestinal hormones during minimal enteral feeding of sick premature
      infants].
AB  - OBJECTIVE: To measure gastrointestinal hormonal response (GHR) with minimal
      enteral feeding (MEF) in sick premature infants. METHODS: Forty-one babies birth
      weight < 1800 g receiving total parenteral nutrition or intravenous solutions
      entered the study. They were distributed in two groups: group I: 26 infants
      (early enteral feeding < or = 5 d) and group II = 15 infants (late enteral
      feeding = 10-14 d). A diluted special formula was used as MEF starting with 1 mL
      hourly with daily increments of 1 mL up to 120 mL. Basal and final determinations
      of GHR were done before and after the MEF. RESULTS: Both groups were similar in
      birth weight, postnatal age, and trophism. There were intragroup differences
      between basal and final GHR for all hormones in both groups. Subgroups by
      gestational age (< or = 32 vs > 32 weeks) and trophism (< or = 1250 vs > 1250 g)
      also showed basal-final differences. There were no complications related to the
      MEF. CONCLUSIONS: MEF favors secretion of gastrointestinal hormones in sick
      premature infants. Early MEF seems to be preferable to late one since it allows a
      faster secretion related to volume of the formula. MEF did not increase abdominal
      complications in our infants.

PMID- 9608789
TI  - [Persistence of critical-reading learning in medical residents].
AB  - OBJECTIVES: 1. To evaluate the persistence of a training course on critical
      reading of medical articles by medical residents seven months after training. 2.
      To compare the persistence of training according to type of training
      (participative vs expositive). METHODS: We used the same groups of first year
      medical residents of a previous study. They had received seven months before a 30
      hours training in the reading of research articles: Group I (N = 28) had a course
      of active participation by reading articles previous to meeting discussions; II
      (n = 17) exposition of research themes by active researchers; III (n = 23) same
      as II but with non-research trainers. Using an examination questionnaire
      developed and validated by us to explore critical reading of research papers, the
      trainees were scored after finishing their training (initial score). Seven months
      later we retested them using the same test (not all were retested: two were
      missing in groups I and III and six in Group II). Non parametric statistics were
      used to compare the groups (Wilcoxon, Kruskal-Wallis, Mann-Whitney). RESULTS:
      There were no intragroup differences of the retesting versus the initial median
      in the three groups (I had 17.5 vs 19 initial, II had 7 vs 13, III had 6 vs 3).
      In the initial testing, Groups I and II scored higher than III, but only Group I
      was higher than the other groups upon retesting (p < 0.006). CONCLUSION: An
      active participatory training to promote critical reading was better than the
      traditional training techniques still widely used.

PMID- 9608790
TI  - [Postoperative analgesia using epidural administration of bupivacaine plus
      lidocaine].
AB  - OBJECTIVE: To compare the postoperative analgesia of bupivacaine + lidocaine
      versus lidocaine in lower abdominal surgery. DESIGN: Randomized clinical trial.
      METHODS: Thirty patients, scheduled for lower abdominal surgery and epidural
      anesthesia (EA) were randomly assigned to receive EA with 30 mg of bupivacaine
      plus 240 mg of lidocaine (group A) or 300 mg of lidocaine (group B). A lumbar
      epidural catheter in L1-L2 or L2-L3 was inserted, and a bolus with total dose was
      given. The periods of latency and postoperative analgesia, the hemodynamic
      variable and the preoperative, intraoperative and postoperative data were
      recorded. RESULTS: Fifteen patients per group were included. There were no
      differences intergroup in age, height, weight, hemodynamic variables and surgical
      data. The period of latency was similar in the groups but postoperative analgesia
      was longer in group A and the postoperative pain scores were higher in group B in
      the first 120 minutes after surgery. There were no serious complications. In
      newborns of cesarean section, the Apgar scores at 1 and 5 minutes after delivery
      were similar in both groups. CONCLUSIONS: The mixture of bupivacaine + lidocaine
      proved be an effective alternative for epidural use in lower abdominal surgery.

PMID- 9608791
TI  - [Diagnosis of breast tumors by scintigraphy versus mammography].
AB  - OBJECTIVE: To compare the efficacy of the breast scintigraphy with 99mTc-MIBI in
      the detection of breast lesions versus mammography. DESIGN: Cross sectional
      study. SETTING: A concentration oncologic hospital in Mexico City. PATIENTS: 56
      women with a biopsy performed due to radiologic suspicion of mammary cancer were
      included as well as 10 normal women. MAIN PROCEDURES: Mammography, breast
      scintigraphy with 99mTc-MIBI, and biopsy were performed. RESULTS: Sensitivity of
      breast scintigraphy was 100% specificity 94.6%, PPV 90% and NPV 100%; sensitivity
      of the mammography was 100%, specificity 54% PPV 52.7%, and NPV 100%.
      CONCLUSIONS: Breast scintigraphy with 99mTc-MIBI showed a higher sensitivity and
      specificity than those of mammography. It was highly reliable for the diagnosis
      of mammary gland malignant lesions.

PMID- 9608792
TI  - [What is known about micronutrients in Mexico].
AB  - OBJECTIVE: To update the information on micronutrients in Mexico regarding: 1.
      The research lines according to priority of the micronutrient, subjects affected,
      and its focus (basic, clinical, epidemiological, operational). 2. The laboratory
      capacity available for micronutrient assays. MATERIAL AND METHODS: We analyzed
      review articles of what has been published on micronutrients in Mexico since
      1950. We also gathered information by questionnaire from the 16 research groups
      working in Mexico in the area of micronutrients. RESULTS: We generated tables
      summarizing the situation of the six micronutrients which we identified as the
      most problematic in Mexico (vitamins A and C, and iron, iodine, zinc and
      calcium). CONCLUSIONS: We reached 10 conclusions related to populations of study,
      research line priorities, and desirable operational studies.

PMID- 9608793
TI  - [Problems and solutions in the interpretation of diagnostic tests].
AB  - The interpretation of diagnostic tests has had a remarkable progress in recent
      years with a tendency towards a more clinical and patient-oriented perspective.
      Here we emphasize the limitations of using the dichotomy positive/negative
      testing or cut-off points for normality in many of our medical decisions. We also
      introduce alternative methods to interpret diagnostic tests, specially in unusual
      circumstances, i.e., in the development of new diagnostic tests that may be
      better than the accepted gold standard or when there is no gold standard. Finally
      we analyze the different interpretations of false negative results that may
      modify the interpretation of subsequent testing in a patient.

PMID- 9608794
TI  - [Survey of professionalism among medical professors in Mexico].
AB  - OBJECTIVE: We explored the type of academic training and labor relationship of
      medical teachers in the schools of medicine in Mexico. METHODS: We considered two
      types of academic training (formal and informal) and of labor relations (primary
      and secondary): we considered a teacher as professional when he or she had formal
      training and a primary relationship with the school. A questionnaire was applied
      to 436 medical professors chosen at random from 10 medical schools (who were
      selected as representatives of the 10 types of medical schools identified by
      crossing characteristics of financing (public vs private), curricula (traditional
      vs modular), size (< 500 vs > or = 500 students) and longevity (established
      before 1970 vs 1970+). RESULTS: Only 2.8% (n = 12) of the teachers had a
      professional standing, and in private schools the proportion decreased to 1.3%.
      CONCLUSIONS: Medical education as a professional activity was seen in very few
      teachers. Medical education in Mexico appears to be a secondary and informal
      activity for a large number of teachers.

PMID- 9608795
TI  - [Classification by levels of clinico-epidemiological research designs].
AB  - The objective was to identify the characteristics of epidemiologic designs
      enabling their classification. A critical review of the literature in the
      clinical epidemiologic area was done to establish the main differences between
      designs. A meeting with experts to discuss this controversial topic and obtain
      criteria by consensus was organized. We propose an integral classification based
      on levels with two fundamental shafts: intervention and explanatory reasoning.

PMID- 9608796
TI  - [Consensus versus dissent in leukemia].

PMID- 9608797
TI  - [English in publications].

PMID- 9608798
TI  - [Current indications for implantable automatic defibrillators].
AB  - Since the first implantation in man in 1980 implantable cardioverter
      defibrillator technology has greatly improved and the number of devices implanted
      has increased considerably in recent years. Non-thoracotomy lead systems and
      biphasic shocks are now the approach of choice, offering nearly a 100% success
      rate. This paper version reviews the current indications for the implantation of
      implantable cardioverter defibrillator and is an upgraded of an article
      previously published by the Arrhythmia's Section of the Spanish Society of
      Cardiology. Recommendations for qualification of centres implanting
      defibrillators and follow up are also addressed.

PMID- 9608799
TI  - [Genetic bases of arrhythmias].
AB  - We have long known that there are diseases which are inherited from the parents,
      but it has not been until this last decade, with the introduction of the
      techniques of molecular biology, that we have been able to study them. These
      techniques have enable us to localize and detect the gene that causes a disease
      in the members of a family. The identification of a disease-causing gene does not
      lead only to the diagnosis and possible treatment of a very select patient
      population (the one with the familial disease), but also to a better
      understanding of the molecular basis and pathogenesis of the non-familial forms
      of the disease. Cardiology, despite having received these techniques more slowly,
      is now completely. Involved in the study of the molecular basis of cardiac
      diseases. The first gene to be mapped was that of hypertrophic cardiomyopathy in
      1989. Since then, advances have been achieved at all levels in familial cardiac
      diseases. Hypertension, atherosclerosis, congenital heart diseases, and
      arrhythmias have all benefitted from the new techniques. Spectacular progress has
      been achieved in understanding familial heart rhythm disturbances, like long QT
      syndrome, both as congenital and acquired diseases. In the last five years 4 loci
      and 3 genes have been identified. The first studies of genetic based therapy have
      shown that in the near future patients with receive medication depending on the
      affected gene. Other familial arrhythmias are presently under study. Loci have
      been detected in some, such as bundle branch block and familial atrial
      fibrillation. At the speed that the techniques are evolving, and with the
      impressive advances of the Human Genome Project, we can expect to find the rest
      of the genes causing familial diseases in the next few years. These results are
      encouraging and clearly indicate the need for genetic diagnosis in all patients
      with these diseases. The diagnostic and therapeutic implications of all these
      discoveries could be of paramount importance.

PMID- 9608800
TI  - [Appraisal of the state of the autonomic nervous system in hypertrophic
      cardiomyopathy by the analysis of heart rate variability].
AB  - INTRODUCTION: The analysis of heart rate variability has been accepted as a non
      invasive method to evaluate the influence of the autonomic nervous system over
      the heart. Although heart rate variability has been used during the last decade
      in several illnesses the studies in hypertrophic cardiomyopathy are scarce.
      OBJECTIVES: We report the activity of the autonomic nervous system in patients
      with hypertrophic cardiomyopathy using the analysis of heart rate variability.
      PATIENTS AND METHODS: Heart rate variability was evaluate by the analyzing 24-h
      ambulatory electrocardiograms (Holter) in 20 patients with hypertrophic
      cardiomyopathy and in 15 controls. This method has been used to measure heart
      rate variability. Spectral analysis of the frequencies were calculated using fast
      Fourier transformation. Spectral heart rate variability was computed as high
      (0.15 to 0.40 Hz) low (0.04 to 0.15 Hz) and total (0.01 to 1.0 Hz). We compared
      the relation between low/high frequency as an index of the
      sympathetic/parasympathetic balance. All data are expressed as mean value +/- SD.
      The unpaired Student t-test was used. A two tailed p valued < 0.05 was considered
      statistically significant. RESULTS: There were no differences in the mean heart
      rates among the patients with hypertrophic cardiomyopathy and normal subjects
      (mean +/- SD: 71 +/- 9 versus 74 +/- 11 beats/minute; p = NS) while there was a
      significant decline in total spectral (mean +/- SD: 7.14 +/- 1.1 versus 7.57 +/-
      0.6 ln [ms2]; p = 0.02) and high (mean +/- SD: 5.22 +/- 0.8 versus 5.63 +/- 1.3
      ln [ms2]; p = 0.04) as well as in low spectral frequency of heart rate
      variability (mean +/- SD: 22 +/- 0.8 versus 5.63 +/- 1.3 ln [ms2]; p = 0.04) in
      patients with hypertrophic cardiomyopathy. There were no differences in the
      low/high frequency component ratio in these patients (mean +/- SD: 1.1 +/- 0.1
      versus 1.2 +/- 0.1 ln [ms2]; p = NS). CONCLUSIONS: These facts suggest that the
      patients with hypertrophic cardiomyopathy have an alteration in the autonomic
      nervous system: sympathetic (low spectral frequencies) and parasympathetic
      activity (high spectral frequencies), although this does not reflect an imbalance
      between sympathetic and parasympathetic activities (relation of low to high
      spectral frequencies).

PMID- 9608801
TI  - [Early discharge in uncomplicated acute myocardial infarction].
AB  - INTRODUCTION AND OBJECTIVES: The length of hospital stay for uncomplicated
      myocardial infarction is still a debatable issue. Our study tries to establish
      the rate of patients amenable early discharged and the safety of this practice.
      PATIENTS AND METHODS: We studied retrospectively the clinical features, in
      hospital events and 30-day follow up of 238 patients discharged early (5 or 6
      days) during the last three years. These patients were compared with the
      remaining group of 929 patients discharged after a conventional stay (mean 10.4
      days) in the same time frame. RESULTS: The mean hospital stay in the early
      discharged group was 5.4 days. They had no ischemic, arrhythmic or haemodynamic
      complications in the acute phase. In the 30-day follow up there was only one
      death (at the 14 th post-myocardial infarction day) and 17 readmissions to the
      hospital, none with re-infarction. By contrast, there were 14 deaths and 43
      readmissions among the patients with the standard stay at the hospital.
      CONCLUSIONS: At least 20% of patients with uncomplicated myocardial infarction
      can be discharged early. This practice seems to be safe in low risk groups, and
      is not associated with a higher rate of complications when compared with longer
      hospital stays.

PMID- 9608802
TI  - [Prognosis of patients with angina pectoris or silent ischemia: exercise 99mTC
      MIBI SPECT].
AB  - INTRODUCTION AND OBJECTIVES: Although different reports have compared the extent
      of the myocardial ischemia in patients with or without angina during exercise
      test, there have been few publications which have studied their prognosis. The
      aim of this study is to analyze the prognostic value of the presence of angina
      during 99mTc-MIBI SPECT in patients with proven coronary artery disease without
      previous myocardial infarction. PATIENTS AND METHODS: We studied 82 patients
      prospectively with at least one coronary stenosis > 70% and with reversible
      perfusion defects in 99mTc-MIBI SPECT (long protocol). Twenty two of these
      patients had angina during exercise test. The extension of ischemia was
      quantified on SPECT and the severity of coronary stenoses on coronary
      angiography. The mean follow-up period was 3.2 years. RESULTS: The angina
      patients showed a significantly lower coronary reserve (exercise duration: 6.3
      min vs 8 min; p = 0.03), a lower maximal O2 consumption (5.8 METs vs 6.2 METs; p
      = 0.04), a higher rate of ST depression > 1 mm (64% vs 19%; p = 0.006) and a
      higher degree of ST depression (0.9 mm vs 0.4 mm; p = 0.01) than those patients
      without angina. There were no significant differences in the extent of ischemia
      in SPECT or in the angiographic severity of coronary disease between either
      groups. During the follow-up period the presence of severe complications
      (myocardial infarction or death) tended to be higher (27% vs 17%; NS) in patients
      with angina and the indication of surgical revascularization was also
      significantly higher (50% vs 17%; p = 0.002) in this group. CONCLUSIONS: Presence
      of angina during 99mTc-MIBI SPECT portends a higher risk of medium and long term
      complications, mainly due to surgical revascularization.

PMID- 9608803
TI  - [Transesophageal echocardiography follow-up of patients operated on using the
      Bono-Bentall technique in aneurysms or dissection of the ascending aorta].
AB  - INTRODUCTION: Increasingly patients are surviving after reconstructive surgery of
      the ascending aorta. These patients require follow-up to detect postoperative
      prognostic markers, such as persistence of the flow in a false lumen, intimal
      rupture, or graft complications. We conducted a study with transthoracic and
      transesophageal echocardiography in order to detect residual abnormalities and
      establish the usefulness of this technique in a group of patients after Bono
      Bentall surgery for ascending aorta pathology. PATIENTS AND METHODS: Twelve
      patients were studied with transthoracic and transesophageal echocardiography,
      four after surgery for annulo-aortic ectasia with severe aortic insufficiency and
      eight for type A aortic dissection. The Bono-Bentall surgical procedure was used
      in all the patients with Cabrol's modification being added in three. RESULTS:
      Seven of the eight (87%) patients with aortic dissection had residual
      abnormalities: five persistence of the distal dissection, one pseudo-aneurysm,
      and one peritubular haematoma. A residual lesion (pseudo-aneurysm) was found in
      just one of the four patients (25%) who underwent surgery for annulo-aortic
      ectasia. The ejection fraction was normal in those patients who had been operated
      on for aortic dissection and depressed in those who had annulo-aortic ectasia (60
      +/- 9 vs 40 +/- 10; p = 0.005). CONCLUSIONS: In patients undergoing surgery with
      the Bono-Bentall procedure there is a high incidence of residual aortic
      abnormalities, especially when the operation is for aortic dissection.
      Transesophageal echocardiography is an ideal diagnostic method for the detection
      and follow up of residual abnormalities after ascending aorta surgery. We believe
      this technique should be included in the periodic follow up of these patients.

PMID- 9608804
TI  - [Hemodynamic deterioration in patients submitted to ablation of the
      atrioventricular node].
AB  - INTRODUCTION: Radiofrequency ablation of the atrioventricular conduction system
      has become an established therapy for patients with drug-refractory atrial
      fibrillation. We observed 14 patients with hemodynamic deterioration related to
      worsening of mitral regurgitation after the procedure. PATIENTS AND METHODS: We
      retrospectively evaluated 256 consecutive patients with drug-refractory atrial
      fibrillation referred for radiofrequency ablation of the AV node and implantation
      of a pacemaker. Because we found hemodynamic deterioration related to worsening
      mitral regurgitation, we compared the clinical history, electrophysiologic and
      echocardiographic data from the patients with hemodynamic deterioration and
      worsening mitral regurgitation (group A) with those without hemodynamic
      deterioration (group B). RESULTS: Fourteen out of 256 patients (group A)
      undergoing ablation of the atrioventricular conduction system deteriorated with
      acute pulmonary edema (3 patients) or congestive heart failure (11 patients) at a
      mean of 6 weeks after the ablation procedure. Four of these patients were
      referred for mitral valve surgery. The length of the procedure and the number of
      applications during ablation were similar in both groups. Compared with group B
      patients, group A patients had significantly higher left ventricular end
      diastolic diameters (64 +/- 6 mm vs 56 +/- 9 mm; p < 0.05) at baseline despite
      similar left ventricular end-systolic diameters, fractional shortening and grade
      of mitral regurgitation (1.15 +/- 1.05 vs 1.11 +/- 0.97). Moreover, whereas no
      change was observed in left ventricular end-diastolic diameter, left ventricular
      end-systolic diameter, fractional shortening and grade of mitral regurgitation in
      group B patients after ablation, group A patients experienced a significant
      increase in left ventricular end-diastolic diameter (64 +/- 6 mm vs 72 +/- 9 mm;
      p < 0.01) and grade of mitral regurgitation (1.15 +/- 1.05 vs 2.90 +/- 1.15; p <
      0.01). In patients operated on no ablation related structural damage to the
      mitral valve apparatus could be detected. The worsening of the mitral
      regurgitation was related to dilation of the mitral valve annulus. CONCLUSIONS:
      Hemodynamic deterioration together with progression of mitral regurgitation is a
      potential complication of ablation of the atrioventricular conduction system.

PMID- 9608805
TI  - [Heart pathology of extracardiac origin. VII. Heart and neoplasms].
AB  - Cardiac alterations of neoplastic diseases can be due to direct invasion produced
      by primary cardiac tumors or more frequently secondary to local compression of
      vascular structures by extracardiac neoplasms, such as superior vena cava
      syndrome. One of the most important alterations is the cardiotoxicity of
      anticancer treatments, either chemotherapy drugs or radiotherapy techniques.
      These treatments cause acute and/or chronic cardiotoxicity that the oncologist
      and the cardiologist must be aware of. For instance, 4.5% to 7% of patients that
      have been treated with anthracyclines may suffer cardiac failure in their
      lifetime. The pathogenesis is still not clear. There is currently a lot of
      research on cardioprotectors, but nowadays the only one approved by the FDA is
      dexrazoxane, which is used on breast cancer patients treated with adriamycin.

PMID- 9608806
TI  - [Contribution of color Doppler in the diagnosis of bilateral ductus arteriosus].
AB  - We report a neonate with distal bilateral ductus arteriosus origin of
      nonconfluent pulmonary arteries which was only diagnosed accurately by 2-D echo
      Doppler color flow mapping in the context of situs ambiguous, univentricular A-V
      connection and pulmonary atresia with normal systemic/pulmonary venous drainage.
      The color flow appearance of this singular vascular anatomy was enhanced after
      prostaglandin administration, which, allowed us to see an image resembling a
      "moustache morphology". At 36 months of age, and after a successful bilateral 4
      mm modified Blalock Taussig shunt implantation by sequential approach, the
      patient is waiting for the next surgical step which will include a restoration of
      the confluence of the pulmonary arteries with bidirectional Glenn operation.
      Brief embryological and differential diagnosis comments are discussed.

PMID- 9608807
TI  - [Acute myocardial infarction secondary to Wegener's granulomatosis].
AB  - Wegener's granulomatosis (WG) is a necrotizing and granulomatous vasculitis that
      usually affects the upper and lower respiratory tract and the kidneys. Cardiac
      involvement is rare although pericarditis, coronary arteritis, myocarditis,
      valvulitis and arrhythmias have been described. Acute myocardial infarction with
      clinical expression is an exceptional complication of Wegener's granulomatosis.
      We report a case of a 30-year-old man with Wegener's granulomatosis who suffered
      an acute myocardial infarction during the initial phase of the disease, following
      seven days of treatment with glucocorticoids and cyclophosphamide. Transthoracic
      echocardiography showed abnormal regional wall motion with septal hypokinesia and
      apical akinesia. Cardiac catheterization revealed an ectasic segment in the
      proximal left anterior descending coronary artery and total occlusion in the mid
      segment. Medical therapy with prednisone and cyclophosphamide was continued. No
      complications and initial remission were achieved.

PMID- 9608808
TI  - [Spontaneous echocardiographic contrast in the left ventricle: apropos of 2
      cases].
AB  - Two cases of spontaneous echocardiographic contrast in the left ventricle, using
      transthoracic echocardiography, are presented. One is due to a low-flow state in
      a patient with a dilated myocardiopathy. In the other we observed the
      echogenicity of a turbulent intracardiac blood flow across a mitral prosthesis.
      We considered the different theories that tried to explain the multiple origin of
      this "smoke".

PMID- 9608809
TI  - [Coronary ischemia during radiofrequency ablation of left lateral accessory
      pathway in an infant].
AB  - Acute coronary ischaemic complications are uncommon following catheter ablation
      of accessory pathways. Only isolated cases have been previously reported in adult
      patients during ablation of left free-wall accessory pathways by retrograde or
      anterograde approach. We report a transient ischaemic complication after catheter
      ablation of a left free wall accessory pathway by transseptal approach in an
      infant.

PMID- 9608810
TI  - [Incidence and risk factors in fractures of the proximal femur due to
      osteoporosis].
AB  - Every year more than one million fractures of the proximal femur occur in the
      world, especially in older persons. Given the continuous aging experienced by
      populations, such fractures will become more frequent from year to year and will
      constitute a growing public health problem. The largest increase is expected to
      occur in countries of Latin America around the year 2050. Since nearly 70% of all
      atraumatic fractures in persons over 45 are due to osteoporosis, a case-control
      study was conducted in the city of Mar del Plata, Argentina, for the purpose of
      investigating the incidence of and the risk factors associated with proximal
      femur fractures due to osteoporosis. Between 1 August 1992 and 31 July 1993, a
      record was kept of all fractures of the proximal femur due to osteoporosis in
      persons over 50 years of age that visited any of the city's 30 public and private
      health centers. A total of 246 cases was recorded. The incidence rate per 100,000
      inhabitants in the above-50 population was 259 among women and 92 among men, for
      a ratio of 2.8:1. The incidence was consistently higher in the older age groups,
      especially in persons over 75. Factors associated with a statistically
      significant increased risk of fracture of the proximal femur were: a history of
      neurologic disorders, psychotherapeutic drug use, alcohol consumption, previous
      fractures, cardiovascular disease, and a decreased intake of milk products. There
      were no observed differences between cases and controls with respect to age at
      menopause, weight, height, previous activity, smoking habits, or sun exposure,
      nor were such differences detected in terms of the percentage of women who had
      undergone oophorectomy.

PMID- 9608811
TI  - [A simplified screening test for the identification of individuals with
      diminished vision in developing countries].
AB  - Simple but effective tests have been produced for screening subjects with low
      vision in developing countries. These tests of distance and near vision, based on
      the E test, were evaluated and validated in trials with people aged 4-90 years,
      and have been field tested in the health, education and rehabilitation services
      in 32 developing countries. Their sensitivity and specificity as screening tools
      for low vision have been calculated: sensitivity of 85% and specificity of 96%
      for the distance vision test, and sensitivity of 100% and specificity of 84% for
      the near vision test. The content and format of the tests have been demonstrated
      to be appropriate for developing countries, and their effectiveness for screening
      for low vision has been confirmed.

PMID- 9608812
TI  - Reducing automobile traffic: an urgent policy for health promotion.
AB  - In recent decades traffic injuries have become a leading cause of death and
      disability the world over. In congested urban areas, the noise and emissions from
      vehicle engines cause discomfort and disease. More than one billion people are
      exposed daily to harmful levels of atmospheric contamination. Because internal
      combustion generates carbon dioxide (CO2), the automobile is a principal
      contributor to the greenhouse effect, which has significantly raised the
      temperature of the atmosphere. Scientists anticipate that in coming decades the
      greenhouse effect will produce alterations in climate that are very likely to be
      harmful and possibly catastrophic. Meanwhile, burgeoning traffic and rural and
      urban highway infrastructures are already among the principal causes of
      environmental degradation. Urban development, because it is nearly always
      "planned" to accommodate automobiles rather than people, reduces the quality of
      life and tears the social fabric. In contrast to private automobiles, public
      transportation, bicycles, and walking produce little environmental contamination
      or injury-related morbidity and mortality. These modes of transport involve more
      physical activity, with its positive health effects, and avoid contributing to
      the greenhouse effect. The reduction of automobile traffic and substitution of
      alternative modes of transport are essential policies for health promotion. They
      should be incorporated in "healthy cities" programs and general economic
      policies.

PMID- 9608813
TI  - Quality assurance of the serologic diagnosis of Chagas' disease.
AB  - A quality assurance program of the Chagas' disease laboratory network of
      Argentina has been conducted by the National Reference Center since 1988, with
      the aim of assessing the reliability of serologic test results. Chagas' disease
      is endemic in Argentina, but the prevalence of seropositivity for Trypanosoma
      cruzi among 18- to 20-year-old men decreased from 5.8% in 1981 to 1.8% in 1994.
      About 600 laboratories form the Chagas' disease laboratory network, with main
      central laboratories in each of the 24 provinces in Argentina. The quality
      assurance program promotes regular use of good laboratory practice and internal
      and external quality control to improve performance of the participants; it also
      provides technical assistance and guidelines. Eventual corrective measures are
      discussed in workshops. Results of the first external evaluation by proficiency
      testing of serum panels and confirmation of results for 58 of the main
      laboratories reveal that from 1988 to 1994 the rate of agreement has increased.

PMID- 9608814
TI  - [Anti-sulfatide antibody titers in patients with chronic Chagas disease and other
      forms of cardiopathy].
AB  - A specific treatment for Chagas' disease has not yet been discovered, even though
      the condition is endemic in large parts of the Region of the Americas. Earlier
      studies have addressed the possibility that the sulfatide galactocerebroside in
      Trypanosoma cruzi behaves as an immunogen involved in the production of the high
      antisulfatide antibody levels found in patients with chronic infestation with the
      parasite. This may be an important factor in the pathogenesis of the cardiac
      symptoms and peripheral neuropathy seen in Chagas' disease, which is the most
      important cause of myocarditis in Central and South America and the second most
      important cause of heart failure in several of the countries located in these
      subregions. The present study was conducted in order to ascertain whether
      patients with Chagas' disease and other patients not afflicted with the ailment
      differ insofar as the presence of antibodies against sulfatide is concerned, and
      it describes antisulfatide antibody levels in 124 hospital patients (74 men and
      50 women) between the ages of 15 and 94 who were in the cardiology unit of Vargas
      Hospital in Caracas from 1 July to 30 June 1995. Antisulfatide antibody titers
      were determined by means of enzyme-linked immunosorbent assays (ELISA), and the
      antigen employed was sulfatide cerebroside obtained from bovine brain tissue. Of
      the 124 patients under study, 39 (31.5%) suffered from Chagas' disease and had
      antisulfatide antibody levels higher than those detected in patients without
      Chagas (P = 0.0298) and in 28 seemingly healthy controls (P = 0.0035). Serum
      levels of antisulfatide antibodies in patients with other forms of heart disease
      were also compared with those seen in the control group, and significantly higher
      levels were found in patients with acute ischemic heart disease (P = 0.0049),
      rheumatic valvular heart disease (P = 0.0075), chronic ischemic heart disease (P
      = 0.0464) and bradiarrythmias (P = 0.0157), and significantly lower ones in
      subjects with hypertensive heart disease (P = 0.0367). These antibody levels
      showed no correlation with clinical or paraclinical variables indicative of the
      degree of cardiac compromise. Our results support the notion that antibodies
      against sulfatide may play a role in the pathogenesis of Chagas' cardiomyopathy
      and other forms of heart disease and should be further studied in an effort to
      determine their potential role in these processes.

PMID- 9608815
TI  - [Declarations issued by the International Committee of Medical Journal Editors in
      conjunction with the Vancouver standards].
AB  - These statements, which are published by the International Committee of Medical
      Journal Editors in conjunction with the Vancouver standards, cover some of the
      legal, ethical, and practical aspects of the publication of research papers, and
      of the comments generated by them, in biomedical journals. Following a definition
      of what constitutes a peer-reviewed journal, the roles of journal owners and
      editors are described, along with those of members of an editorial board, and
      procedural norms are set forth in connection with conflicts of interests,
      retractions or corrections, fraud, and breaches of confidentiality. Among the
      last topics explored are the problems involved in the dissemination of research
      results by the popular media, the handling of advertising within the journal, and
      the simultaneous acceptance of manuscripts whose authors have arrived at opposite
      conclusions regarding the results of a particular study.

PMID- 9608816
TI  - [Changes in the geometry of the heart cavities in patients with cardiac tamponade
      undergoing pericardial drainage].
AB  - OBJECTIVES: The objective of our study was to evaluate the changes in cardiac
      chamber dimension--longitudinal and transversal axis--in patients with cardiac
      tamponade after drainage of the pericardial effusion. STUDY DESIGN: This is a
      five year retrospective study (from 1991 to 1995 inclusive) which evaluates
      patients with cardiac tamponade from a clinical and electrocardiographic, as well
      as echocardiographic, point of view. MATERIALS AND METHODS: Thirty-nine
      consecutive patients with cardiac tamponade were evaluated clinically and by ECG
      and two-dimensional echocardiography, before and after drainage of the
      pericardial effusion. The drainage was done by pericardiocentesis alone in 28
      cases (72%), pericardiocentesis followed by surgery in seven cases (18%) and
      surgery alone in four cases (10%). MAIN RESULTS: After drainage we observed a
      reduction in the diameter of the pericardial effusion from 30.1 +/- 8 to 8.1 +/-
      7 mm; the occurrence of jugular vein turgescence decreased from 87% to 5% (p <
      0.001) and heart rate also decreased from 100 +/- 20 beats/minute to 79 +/- 17
      beats/minute (p < 0.001). Systolic blood pressure increased from 107.8 +/- 20.4
      mmHg to 134.6 +/- 20.3 mmHg (p < 0.001). All longitudinal and transversal
      diameters of the cardiac chambers increased after drainage. The greatest increase
      was observed in the transversal diameters of the right chambers. CONCLUSIONS:
      Cardiac tamponade affects both right and left cardiac chambers which are affected
      in their transversal as well as longitudinal diameters; the effect of compression
      was more marked in the right chambers and in the transversal diameters.

PMID- 9608817
TI  - [Tracking indices of the blood pressure in a longitudinal study in infants and
      adolescents].
AB  - OBJECTIVE: The objective of this study was to assess the degree of BP Tracking
      from childhood to adulthood and to evaluate whether high BP levels persist over
      time and progress to adult hypertension. PATIENTS AND METHODS: Two hundred and
      twenty-two healthy schoolchildren living in the North of Portugal were assessed
      at 17 year intervals, starting in 1979 (cohort 1) aged 5 to 18 years, and again
      in 1996 (cohort 2). Tracking indices (Ti) were calculated as follows: Ti = (2x +
      y-z) /N/0.89, where x, y and z refer to the total number in the same, adjacent
      and remote trisections, respectively, and N = x + y + z. If Ti > 1 there is
      positive tracking. RESULTS AND CONCLUSIONS: For systolic and diastolic blood
      pressure, all Ti were greater than 1.0. All individuals that remained in the 3rd
      tertil, 17 years later, weigh more and are more obese than those of the 1st
      tertil. 56.6% of the individuals that belong to the 3rd tertil are now
      hypertensive, which means that a significant percentage of the children with high
      blood pressure in the first survey will be hypertensive in the future.

PMID- 9608818
TI  - [Pulmonary embolism: a clinical case documented, in acute setting, using
      pulmonary scintigraphic perfusion].
AB  - The acute clinical evolution is presented of a patient with previous myocardial
      infarction who was admitted for dyspnea and chest pain. Acknowledging the
      possibility of a new ischemic event, confronted with aortic dissection or
      pulmonary embolism, the clinical investigation is described up to the
      scintigraphic diagnosis of pulmonary embolism. The clinical presentation,
      diagnostic investigation and therapeutic decisions are discussed, with emphasis
      on the usefulness of pulmonary scintigraphy.

PMID- 9608819
TI  - [Rhabdomyoma of the right ventricle associated with Behcet disease simulating the
      presence of a malignant tumor].
AB  - OBJECTIVE OF THE STUDY: To present the clinical case of a patient suffering from
      a rhabdomyoma associated to Behcet's disease. PATIENTS: A 35-year-old man with a
      history of high fever associated to oral ulcers, sinus tachycardia, leukocytosis
      and a high erythrocyte sedimentation rate. Physical examination, chest x-ray,
      blood chemistry, serology and rheumatic tests were normal. Seriate sputum
      cultures, urocultures and blood cultures were negative. The echocardiogram showed
      a non-obstructive mass in the right ventricle, which was confirmed by magnetic
      resonance imaging. INTERVENTIONS: Resection of the tumor under cardiopulmonary
      bypass. After the post-operative recurrence of the fever and the appearance of
      genital ulcers, the diagnosis of Behcet's disease was made. Two and a half years
      after the operation the patient remains asymptomatic under treatment with
      colchicine. CONCLUSIONS: The clinical setting suggested a malignant tumor of the
      right ventricle but the pathological findings showed an adult rhabdomyoma. The
      rarity of finding a rhabdomyoma in an adult is stressed, as well as its
      association with Behcet's disease.

PMID- 9608820
TI  - [The Internet and Cardiology].

PMID- 9608821
TI  - [Current perspectives in screening for cardiac diseases which most frequently
      cause sudden death during the practice of a sports activity].
AB  - Sudden death during sports activities is extremely rare in athletes and
      sportsmen. Its occurrence was calculated at 0.77 to 13 deaths per 100,000
      sportsmen/year. The most frequent causes were coronary heart disease, coronary
      muscular bridges, congenital coronary artery anomalies, subarachnoid hemorrhage,
      hypertrophic cardiomyopathy, arrhythmogenic right ventricular dysplasia, Marfan
      syndrome, aortic coarctation, myocarditis, pulmonary embolism, aortic stenosis,
      mitral valve prolapse and WPW syndrome. Clinical examination nearly identifies
      all cases of aortic stenosis, mitral valve prolapse with regurgitation, and
      aortic coarctation but misses the majority of cases of hypertrophic
      cardiomyopathy and coronary artery diseases. The use of Chest x-rays, ECG, Stress
      Test and Echocardiogram will provide the identification of most cases with
      increased risk of death. Although costs are not limited for professional
      athletes, this strategy does not totally overcome the problem because diagnostic
      errors are frequent (false positives and false negatives). Therefore it is
      important to admit the failure of these screening procedures and the necessity to
      adapt the strategy to cost-efficiency and time-efficiency in this population.

PMID- 9608822
TI  - [The Medico-Social Cardiology Center of Coimbra. History and epilogue].
AB  - The Medico-Social Cardiology Center of Coimbra, designed and founded by Joao
      Porto in 1941, played a remarkable (and pioneering) role in helping cardiac
      patients in the central part of Portugal. Its work was made possible by the
      commitment of many doctors, nurses and Social Center Bulletins. For a quarter of
      a century the number of medical and social interventions in favor of cardiac
      patients is truly remarkable. Meanwhile, improvements in the national social
      services--easier access to medical services, free semiology exams, subsidized
      drugs, state illness subsidies--caused a reduction of monetary contributions from
      both partners and wealthier and healthier cardiac patients. Little by little the
      Center's activity was reduced, which ultimately led to its recent dissolution.
      The Center's books were placed in the Archive of the University and its assets
      (bank deposits) were donated to the Association for the Development of Cardiology
      at the University Hospital in Coimbra. As its name suggests, the main goal of
      this non-profit association consists in the promotion of scientific and
      technological improvement of the Cardiology Department at the University Hospital
      of Coimbra.

PMID- 9608823
TI  - [Hibernating myocardium. An incomplete adaptation to ischemia].
AB  - BACKGROUND: We tested the hypothesis that hibernating myocardium represents an
      incomplete adaptation to a reduced myocardial oxygen supply. METHODS AND RESULTS:
      In 38 patients, areas of hibernating myocardium were identified by angiography,
      multigated radionuclide ventriculography, thallium scintigraphy with reinjection,
      and low-dose dobutamine echocardiography. Biopsies removed at cardiac surgery
      showed structural degeneration characterized by a reduced protein and mRNA
      expression and disorganization of the contractile and cytoskeletal proteins
      myosin, actin, desmin, titin, alpha-actinin, and vinculin by electron microscopy,
      immunohistochemistry, and in situ hybridization. Additionally, an increased
      amount of extracellular matrix proteins resulting in a significant degree of
      reparative fibrosis was present. Dedifferentiation, i.e., expression of fetal
      proteins, was absent. Apoptosis indicating suicidal cell death was found by the
      terminal deoxynucleotidyl transferase end-labeling method and electron
      microscopy. Radionuclide ventriculography showed improvement of regional function
      at 3 months postoperatively compared with preoperative values (mean values, 23.5%
      and 48%, respectively), and the echocardiographic wall-motion score index
      decreased from 3.4 to 1.8. The degree of severity of the morphological changes
      (three stages) correlated well with the extent of postoperative functional
      recovery: more advanced clinical improvement was observed in patients with slight
      and moderate morphological degeneration (stages 1 and 2), but recovery was only
      partial in severe degeneration (stage 3). CONCLUSIONS: Cellular degeneration
      rather than adaptation is present in hibernating myocardium. The consequence is
      progressive diminution of the chance for complete structural and functional
      recovery after restoration of blood flow. The practical consequence from this
      study should be early revascularization in patients showing areas of hibernating
      myocardium.

PMID- 9608824
TI  - Pharmacokinetics of beta2-sympathomimetics at the example of fenoterol and
      conclusion for the administration.
AB  - The pharmacokinetics of fenoterol (salbutamol, terbutaline) after systemic
      administration (i.v., infusion, nasal administration) can be best described by a
      three-compartmental model. Nasal administration causes an effect-time profile
      between that of infusion and inhalation. The effects of nasal administration on
      the lung function and the heart rate depend on the plasma levels of the beta2
      agonist. The absorption rate after inhalation differs individually in a large
      variability (1-27% of the dosage). After inhalation the effect on the lung
      function does not depend on the absorption rate nor on the plasma levels of the
      beta2-agonist. After inhalation the effect on the lung function is three- to
      fivefold more expressed than predictable from the plasma level. From the pk/pd
      data it can be assumed, that there are 10-20 fold higher concentrations in the
      airways than in the plasma. It is assumed that there are structures nearby the
      beta2-receptor responsible for the long-lasting effect observed after inhalation.
      These depot structures cannot be reached from the plasma in concentrations needed
      for bronchodilation under in vivo conditions. In respect to the effect/side
      effect relations, there is no doubt that inhalation is the optimal solution for
      administering beta2-agonists. In respect to the effect/side effect relations more
      frequent administration of small doses seems to be more favourable than high
      doses inhaled in long periods.

PMID- 9608825
TI  - The hypoxaemia in chronic obstructive pulmonary disease (COPD) and its
      management.
AB  - Chronic hypoxaemia < or = 55 mmHg, induces various clinical and physiological
      consequences in patients with stable COPD: dyspnoea, decrease in exercise
      performances, erythrocytosis impairment of neuropsychological functions,
      pulmonary hypertension, right ventricular heart failure, all of these troubles
      impairing quality of life and vital prognosis. To restore a PaO2 > 60 mmHg (or
      SaO2 > 90%), long term oxygen therapy (LTOT) is the best method in the management
      of COPD with severe chronic respiratory failure. For patients with PaO2 55-70
      mmHg. Almitrine bismesylate a piperazine derivative improving the
      ventilation/perfusion matching, used in low dosage and in sequential
      administration, is a useful drug to increase the PaO2 and so, to delay but not to
      avoid LTOT in responder patients when PaO2 remains < or = 55 mmHg.

PMID- 9608826
TI  - [Digital goniometry "Spasmometr GC-2"].
AB  - The review of modern application of goniometric assessment in rehabilitation of
      patients with movement organs system disorders is done by the authors. The
      construction and principle of operation of digital goniometer, applied to
      pendulum testing of lower extremities with pathologic changed muscle tone, are
      described. An electro-optical transducer transmits the digitized time-dependent
      function of an angle between the thigh and leg axes of subject via an interface
      to the special computer programme. The function is registered, some coefficients
      describing extremity motion in joint are determined and the patient is assigned
      to the proper rehabilitation group by the composed programme. Normal values of
      the pendulum test coefficients in the asymptomatic subjects are performed.

PMID- 9608827
TI  - [Use of intraoperative fiber-esophagoscopy in surgical treatment of rare
      esophageal diseases].
AB  - The aim of our study is to discuss our observations concerning surgical treatment
      of rare diseases of the oesophagus. 10 patients were operated on, 6 cases with
      benign tumours (including leiomyoma, Abrikossoff tumour, polyp of oesophageal
      mucose), 2 with intramural bronchogenic cysts of the oesophagus, 1 with benign
      stricture after inflammation and 1 with stricture of oesophagogastric anastomosis
      after Akiyama operation. In 6 cases tumour was resected without opening of the
      oesophageal lumen (enucleation), in 4 patients with tumours located on one of the
      walls, the wedge resection, transversely to the long oesophageal axis was
      performed. In cases with tumour located in mucose (Abrikossoff tumour, polyp,
      post-inflammatory scar), intraoperative fiber-esophagoscopy was conducted
      simultaneously to enable the exact localisation of tumour and evaluation of
      radical resection. There were no postoperative complications and dysphagia showed
      regression. The remote results (from 1 year to 6 years) have been found to be
      satisfactory. CONCLUSIONS: 1. The procedure of choice in the treatment of the
      intramural cysts and benign tumour of the oesophagus is enucleation and wedge
      resection with suture in layers in the tumour located in mucose. 2.
      Intraoperative fiber-esophagoscopy enables the exact lesion localisation and
      evaluation of radical resection.

PMID- 9608828
TI  - [Mobilization of the pulmonary hilus from the pericardium in plastic surgery of
      the bronchi].
AB  - Since February 1990 to May 1996 we performed 69 operations of "sleeve resection"
      of the bronchi. "U" shape interior in pericardium was made below inferior
      pulmonary vein. Additionally, on the right side the inferior vena cava was
      mobilized. In this way 5 cm movement upwards of the pulmonary hilus was possible.
      Healing of the bronchial anastomosis was proper in each case. We conclude that
      performance of bronchial anastomosis without any tension in suture line is the
      most important factor for obtaining good healing of the bronchi.

PMID- 9608829
TI  - [Long-term results of surgical treatment in patients with lung neoplasms
      depending on the time of diagnosis].
AB  - In this work we did an analysis of the correlation between duration of lung
      cancer symptoms before operation and the stage of disease and long-term results
      of treatment. 181 pts were examined and 5-year survival was evaluated after
      surgical treatment. We found that it took from 2 weeks to 2 years and average 4,6
      months, from the first clinical symptoms of lung cancer and occasional detection
      in X-ray examination till the moment of surgical treatment. We also noticed that
      long term results depended on the stage of disease of the surgically treated pts.

PMID- 9608830
TI  - [Preliminary treatment results of relapsed or refractory acute leukemia using two
      and three drug regimens].
AB  - 36 patients with relapsed (29) or refractory (7) acute lymphoblastic or
      nonlymphoblastic leukaemia received regimens employing 1-3 courses of
      mitoxantrone (or idarubicin), intermediate doses of cytarabine and etoposide.
      Complete remission (CR) was achieved in 30% of patients (5/15 ALL, 6/21 AML, 5
      cases of refractory and 6 of relapsed leukaemia). Duration of CR was 3-6+ months
      (3 patients are still alive). Toxicity of the treatment was acceptable, however 5
      patients with severe granulocytopenia died from sepsis.

PMID- 9608831
TI  - [Diagnosis of infectious mononucleosis in children].
AB  - Clinical course of infectious mononucleosis was analysed in 36 children.
      Heterophilic antibodies were found in 27.8% of children at the age of six or
      less, and in 72.2% of older ones, mainly between 5-15 day of disease. Mild,
      mainly haematological complications occurred in 13.8% of cases.

PMID- 9608832
TI  - [Usefulness of ultrasonographic tests for localizing changes in peri-thyroid
      nodes in patients with malignant lymphomas].
AB  - 9 cases initially suspected of toxic nodular disease were proved to be Hodgkin
      disease in 8 and lymphoma in one. Sonographic exams of the neck revealed enlarged
      peri-thyroid nodes in all cases. Biopsy of these nodes and histopathological
      examinations of the nodes confirmed the diagnosis.

PMID- 9608833
TI  - [Most frequent causes and treatments of urinary tract infections in children].
AB  - The pathogenesis and frequency of the urinary tract infections in children were
      introduced. I evaluated the consequences of the infections in children with
      congenital anomalies of the urinary tract. I also mentioned the possibilities of
      treatment and its results.

PMID- 9608834
TI  - [Necrotizing dermatitis, infections of soft tissue and deep fascia:
      classification and treatment].
AB  - Nectrotizing fasciitis is a mixed infection of skin and subcutaneous tissue with
      a characteristic clinical and pathological appearance. Necrotizing soft tissue
      infections, caused by aerobic, anaerobic and mixed bacterial flora are an
      increasing problem in medical and surgical practice. The apparently wide variety
      of these infections is systematized. Etiology and bacteriology are discussed, as
      the role of surgery, antibiotics and hyperbaric chamber in the treatment of the
      infections. Early and radical surgical excision of all affected tissue is the
      treatment of choice. Adjuvant hyperbaric oxygen appears to be important in
      refractory progressive bacterial gangrene. A combination of hyperbaric oxygen,
      surgical treatment and antibiotics gives the lowest mortality and morbidity in
      gas gangrene compared with other treatment modifications. Extensive clinical
      experience shows the efficacy of these treatment protocols.

PMID- 9608835
TI  - [The role of carnitine in human lipid metabolism].
AB  - Carnitine is an important nutrient that is present in diet (particularly in meat
      and dairy products) and is synthesized from amino acids. Carnitine has two
      principal functions in the organism. One is to transport long-chain fatty acids
      into the mitochondrion. The second function of carnitine is to regulate the
      intramitochondrial ratio of acylocoenzyme A to free coenzyme A. This function is
      important because it allows to remove excessive (and potentially toxic) short-
      and medium-chain fatty acids from the mitochondrion, and because it maintains
      sufficient free coenzyme A within the mitochondrion to support energy metabolism.

PMID- 9608836
TI  - [Restenosis after percutaneous coronary angioplasty--cause, prevention
      strategies].
AB  - PTCA is a new method of invasive cardiology. Restenosis is an important
      limitation of efficacy of this method. It occurs in 20-45% of patients.
      Pathomechanism of the restenosis is not clear. It is assumed, that restenosis is
      an answer of the endothelium to the procedure. This response consists of the
      inflammation, platelet primary adhesion and aggregation, proliferation of smooth
      muscle cells and intercellular matrix production. These changes together with old
      atheroma and thrombus create a new stenosis. There were many attempts to prevent
      restenosis based on the pathophysiology, but so far no successful method has been
      found.

PMID- 9608837
TI  - [Treatment of anxiety disorders].
AB  - The paper presents current methods of treatment of anxiety disorders:
      psychotherapeutic and pharmacologic. Therapy of panic disorder differs from
      therapy of generalised anxiety disorder, the two main categories of anxiety
      disorders. An anxiety often is present in somatic diseases. Benzodiazepines are
      the most often used medicines against anxiety.

PMID- 9608838
TI  - [Diagnostic difficulties in a case of malignant carcinoma of the small intestine.
      Clinical reports].
AB  - The paper presents clinical findings in four patients with malignant tumours
      originally arising from the jejunum, which have been diagnosed and surgically
      treated in the Department of Alimentary Tract Surgery during the last six years.
      Diagnostic problems and the patients' postoperative course have been presented.
      One patient had a metastatic malignancy which turned out to be the Sister Mary
      Joseph tumour.

PMID- 9608839
TI  - [Remembrance of Professor Rudolf Weigl].

PMID- 9608840
TI  - [Computer program "PANCREAS"].
AB  - Contemporary computer technology allows precise and fast large database analysis.
      Widespread and common use depends on appropriate, user friendly software, usually
      lacking in special medical applications. The aim of this work was to develop an
      integrated system designed to store, explore and analyze data of patients treated
      for pancreatic cancer. For that purpose the database administration system MS
      Visual Fox Pro 3.0 was used and special application, according to ISO 9000 series
      has been developed. The system works under MS Windows 95 with possibility of easy
      adaptation to MS Windows 3.11 or MS Windows NT by graphic user's interface. The
      system stores personal data, laboratory results, visual and histological analyses
      and information on treatment course and complications. However the system
      archives them and enables the preparation reports of according to individual and
      statistical needs. Help and security settings allow to work also for one not
      familiar with computer science.

PMID- 9608841
TI  - Detection of conformational changes in an immobilized protein using surface
      plasmon resonance.
AB  - Utilizing surface plasmon resonance (SPR), we have developed novel methodology
      for the detection of conformational change(s) in immobilized proteins. A
      genetically altered E. coli dihydrofolate reductase (DHFR-ASC) was attached to a
      carboxymethyldextran matrix layer covering the sensor surface of an SPR biosensor
      through a disulfide linkage at the engineered protein's C-terminus. The DHFR-ASC
      immobilized surface exhibited a larger response to acid treatment than reference
      surfaces lacking immobilized proteins. The SPR signal of the tethered protein and
      the molar ellipticity of DHFR-ASC in solution responded similarly to pH changes,
      consistent with the interpretation that changes in the SPR signal reflect
      conformational changes occurring during acid denaturation. A pH shift observed
      between the SPR signal and ellipticity changes may reflect a difference between
      surface and bulk pH. The tethered protein sensor surface was stable to repeated
      acid treatment using solutions in the pH range of 0.12-7.80 and yielded
      reproducible measurements. This is the first demonstration of detection of
      conformational changes in an immobilized protein using an SPR biosensor. This
      technique has potential for developing novel sensors and/or switching devices in
      response to protein conformational changes.

PMID- 9608842
TI  - Tapered optical fiber sensor using near-infrared fluorophores to assay
      hybridization.
AB  - We present an all-fiber hybridization assay sensor that relies on the evanescent
      field excitation of fluorescence from surface-bound fluorophores. The evanescent
      field is made accessible through the use of a long, adiabatically tapered single
      mode fiber probe. A laser diode with a 785-nm wavelength is used in a pulsed mode
      of operation to excite fluorescence in the tapered region of a fiber probe using
      the near-infrared fluorophore IRD 41. We have used various chemical treatments to
      prepare the tapered fiber surface for chemical, as well as physical, binding of
      fluorophores. We have carried out real-time hybridization tests for IRD 41
      labeled oligonucleotide, at various probe concentrations, binding to
      complementary oligonucleotide cross-linked to the tapered fiber surface. The
      biospecificity of our sensor is confirmed through hybridization tests with a
      control oligonucleotide. Short oligonucleotides (20-mer) bound to the fiber
      surface have been used to detect near-IR dye-labeled complementary sequences at
      subnanomolar levels. Sandwich assays with Helicobacter pylori total RNA were
      conducted to examine the capability of the biosensor for detecting bacterial
      cells using rRNA as the target. The results indicate that this fluorosensor is
      capable of detecting H. pylori in a sandwich assay at picomolar concentrations.

PMID- 9608843
TI  - Monitoring protein refolding induced by disulfide formation using capillary
      isoelectric focusing-electrospray ionization mass spectrometry.
AB  - Rapid growth in the biotechnology industry has led to a dramatic increase in
      attention to the protein folding problem. Understanding protein-folding pathways
      is essential to the production of biopharmaceuticals since commercial production
      of recombinant proteins often requires a protein-refolding process for recovery
      of high yields. Protein folding coupled to the formation of disulfide bonds
      presents one of the simplest approaches to studying folding intermediates. On
      line capillary isoelectric focusing-electrospray ionization mass spectrometry
      (CIEF-ESIMS) is demonstrated for kinetic studies of disulfide bond-induced
      protein refolding. Refolding intermediates of bovine pancreatic ribonuclease A, a
      model system for this study, are blocked at different stages by alkylating free
      thiols with iodoacetate. The alkylation reaction results in the introduction of
      charge (-1) and mass (59) differences for each alkylation site, providing the
      means for predictable separation and direct identification of refolding
      intermediates using CIEF-ESIMS. Besides the observation of refolding
      intermediates containing different numbers of disulfide bonds and even mixed
      disulfides, the two-dimensional resolving power of CIEF-ESIMS allows the
      determination of conformational heterogeneity among groups of refolding
      intermediates.

PMID- 9608844
TI  - Identification of phosphorylation sites in proteins separated by polyacrylamide
      gel electrophoresis.
AB  - We report a fast, sensitive, and robust procedure for the identification of
      precise phosphorylation sites in proteins separated by polyacrylamide gel
      electrophoresis by a combination of matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry (MALDI/TOF) and online capillary liquid
      chromatography electrospray tandem ion trap mass spectrometry (LC/ESI/MS/MS).
      With this procedure, a single phosphorylation site was identified on as little as
      20 ng (500 fmol) of the baculovirus-expressed catalytic domain of myosin I heavy
      chain kinase separated by gel electrophoresis. The phosphoprotein is digested in
      the gel with trypsin, and the resulting peptides are extracted with > 60% yield
      and analyzed by MALDI/TOF before and after digestion with a phosphatase to
      identify the phosphopeptides. The phosphopeptides are then separated and
      fragmented in an on-line LC/ESI ion trap mass spectrometer to identify the
      precise phosphorylation sites. This procedure eliminates any off-line HPLC
      separation and minimizes sample handling. The use of MALDI/TOF and LCQ, two types
      of mass spectrometers that are widely available to the biological community, will
      make this procedure readily accessible to biologists. We applied this technique
      to identify two autophosphorylation sites and to assign at least another 12
      phosphorylation sites to two tryptic peptides in a series of experiments using a
      gel slice containing only 200 ng (3 pmol) of human double-stranded RNA-activated
      protein kinase expressed in a mutant strain of the yeast Saccharomyces
      cerevisiae.

PMID- 9608845
TI  - Characterization of heparin oligosaccharide mixtures as ammonium salts using
      electrospray mass spectrometry.
AB  - Among glycosaminoglycans, polysulfated heparin chains provide the greatest
      challenge to characterization due to high polarity, structural diversity, and
      sulfate lability. The present report demonstrates how electrospray mass
      spectrometry (ESMS) can be used to derive compositional information from pure and
      mixed fractions of heparin tetra- to decasaccharide fragments prepared by
      controlled digestion of heparin with heparinase I. It also describes an improved
      procedure for fractionation of heparin oligosaccharides up to
      octadecasaccharides. Ammonium salts prove to be superior to sodium salts,
      particularly for analysis of mixed components. In the mass spectrum of a
      hexasaccharide fraction, the identification of six major mass peaks that
      represent the known hexasaccharide structures confirms that ESMS analysis of
      heparin oligosaccharide fragments gives a close representation of their
      constituent composition. In addition to the previously identified components,
      several unreported oligosaccharides were detected in the spectra of octa- and
      decasaccharide fractions. The ESMS identification of the three major species in a
      decasaccharide fraction was confirmed after HPLC subfractionation and reanalysis.
      ESMS detection sensitivity of low picomole amounts of oligosaccharides can be
      readily achieved.

PMID- 9608846
TI  - Analysis of DNA fragments from conventional and microfabricated PCR devices using
      delayed extraction MALDI-TOF mass spectrometry.
AB  - Applications of polymerase chain reaction (PCR) product analysis using rapid
      affinity capture followed by delayed extraction (DE) MALDI-TOFMS is presented.
      Such applications include multiplex short tandem repeat (STR) typing, which is
      demonstrated for STR systems from conventional and microchip-based thermal
      cycling instruments. Using the combination of the microfabricated PCR instrument
      and DE-MALDI-TOFMS, a complete genotyping assay can be performed in under 50 min
      with a resultant molecular weight accuracy approaching or exceeding 100 ppm
      through external calibration. The observed resolution and mass accuracy for a 69
      base PCR product enables identification of single base substitutions by direct
      molecular weight determination.

PMID- 9608847
TI  - Estimation of the partitioning characteristics of drugs: a comparison of a large
      and diverse drug series utilizing chromatographic and electrophoretic
      methodology.
AB  - 1-Octanol-water log P values for a large number of standards and bioactive
      molecules have been correlated to the logarithm of the corresponding capacity
      factors determined by reversed-phase high-performance liquid chromatography,
      using a novel dynamically coated phase, containing phosphatidylcholine. Similarly
      a correlation was also obtained for log P and capacity factors determined by
      micellar electrokinetic capillary chromatography (MECC), involving the use of
      phosphatidylcholine--bile acid mixed micelles in the separation buffer.
      Statistical analysis of data obtained via both methods has shown that either
      method will give reliable log P predictions, although MECC is generally more
      useful for neutral and basic compounds. It is recommended that, as both methods
      can easily be set up in an analytical laboratory, their combined use provides
      rapid methodology for the confident estimation of hydrophobicity, as measured by
      log P for the widest diversity of chemical structures.

PMID- 9608848
TI  - Reverse micelle formation for acceleration of the supercritical fluid extraction
      of cholesterol from food samples.
AB  - Reverse micelle formation is presented as a new strategy for improving the
      extraction of polar species with supercritical (SC) CO2. The addition of a
      reverse-micelleforming reagent prior to SFE accelerates the quantitative
      extraction of the analyte. The effect was used to develop a method for the
      determination of cholesterol in solid foods. The proposed method involves the
      addition of a microemulsion of a nonionic surfactant (Triton X-100) to the sample
      and dynamic extraction with SC-CO2 at 383 bar and 40 degrees C for 20-40 min. The
      method was validated using a certified reference material (NIST-SRM 1845) and was
      subsequently used to analyze low-cholesterol (whole bread, oat biscuits, orange
      biscuits) and high-cholesterol foods (semiskimmed and whole milk) with excellent
      results (RSD < 11% in all instances).

PMID- 9608849
TI  - Automatic and simultaneous analysis of Lens culinaris agglutinin-reactive alpha
      fetoprotein ratio and total alpha-fetoprotein concentration.
AB  - An automated analytical method for analyzing alpha-fetoprotein (AFP) carbohydrate
      chain microheterogeneity based on competitive reaction between lectin and anti
      AFP monoclonal antibody in liquid phase is described. The antibody used binds to
      all species of AFP molecule without Lens culinaris agglutinin (LCA); however, its
      binding reaction to LCA-reactive AFP was inhibited by LCA. Sulfated tyrosine
      octamer was conjugated to the antibody, and sulfated tyrosine pentamer and
      peroxidase were conjugated to other monoclonal antibodies, respectively. Serum
      reacted with three anti-AFP monoclonal antibodies and LCA in liquid phases, and
      two types of immune complex were observed. The two types were separated directly
      by the liquid-phase binding assay system equipped with an anion-exchange column.
      Peroxidase activity of immune complex was determined fluorophotometrically. Total
      AFP concentration and the ratio of LCA-reactive AFP in samples were calculated
      simultaneously, using the sum of the two peaks and the ratio of peaks obtained by
      LCA inhibition to sum of two peaks. The results correlated well with conventional
      methods. The method is simple and convenient for routine clinical assays.

PMID- 9608850
TI  - Solid-state DNA sizing by atomic force microscopy.
AB  - Atomic force microscopy (AFM) allows rapid, accurate, and reproducible
      visualization of DNA adsorbed onto solid supports. The images reflect the lengths
      of the DNA molecules in the sample. Here we propose a solid-state DNA sizing
      (SSDS) method based on AFM as an analytical method for high-throughput
      applications such as finger-printing, restriction mapping, +/- screening, and
      genotyping. For this process, the sample is first deposited onto a solid support
      by adsorption from solution. It is then dried and imaged under ambient conditions
      by AFM. The resulting images are subjected to automated determination of the
      lengths of the DNA molecules on the surface. The result is a histogram of sizes
      that is similar to densitometric scans of DNA samples separated on gels. A direct
      comparison of SSDS with agarose gel electrophoresis for +/- screening shows that
      it produces equivalent results. Advantages of SSDS include reduced sample size
      (i.e., lower reagent costs), rapid analysis of single samples, and potential for
      full automation using available technology. The high sensitivity of the method
      also allows the number of polymerase chain reaction cycles to be reduced to 15 or
      less. Because the high signal-to-noise ratio of the AFM allows for direct
      visualization of DNA-binding proteins, different DNA conformations, restriction
      enzymes, and other DNA modifications, there is potential for dramatically
      improving the information content in this type of analysis.

PMID- 9608852
TI  - Nonlinear dynamics of the blood flow studied by Lyapunov exponents.
AB  - In order to gain an insight into the dynamics of the cardiovascular system
      throughout which the blood circulates, the signals measured from peripheral blood
      flow in humans were analyzed by calculating the Lyapunov exponents. Over a wide
      range of algorithm parameters, paired values of both the global and the local
      Lyapunov exponents were obtained, and at least one exponent equaled zero within
      the calculation error. This may be an indication of the deterministic nature and
      finite number of degrees of freedom of the cardiovascular system governing the
      blood-flow dynamics on a time scale of minutes. A difference was observed in the
      Lyapunov dimension of controls and athletes.

PMID- 9608851
TI  - Accuracy of the one-point in vivo calibration of "wired" glucose oxidase
      electrodes implanted in jugular veins of rats in periods of rapid rise and
      decline of the glucose concentration.
AB  - The hypothesis of the feasibility of one-point in vivo calibration of
      intravenously implanted glucose sensors during periods of rapid rise and decline
      of venous blood glucose concentration was tested. Miniature (5 x 10(-4) cm2 mass
      transporting area) glucose electrodes with 10-90% response times < 2 min, that
      did not consume oxygen, were implanted in jugular veins of systemically
      heparinized rats and used in 4-h experiments, during which the blood glucose
      concentration was amperometrically monitored. The glucose electrodes were made by
      electrically connecting ("wiring") reaction centers of glucose oxidase through an
      electron-conducting redox hydrogel to gold electrode surfaces. The redox polymer
      and enzyme constituting the electrode sensing layer were immobilized by cross
      linking, and thus the electrodes had no diffusional and readily leached redox
      mediator. One hour after their implantation, the electrodes accurately tracked
      the blood glucose concentration when calibrated in vivo by a one-point
      calibration, when the glucose concentration was steady, when rising rapidly, and
      when declining steeply. For an assumed 2-min lag time, the sensor readings were
      well correlated with the true blood glucose concentrations, with linear
      regression analysis yielding a slope of 0.97 +/- 0.07 and an intercept (bias) of
      0.3 +/- 0.3 mM. The correlation coefficient, r2, was 0.949 +/- 0.020, and the
      percent difference through the 2-22 mM range was 1.9 +/- 1.0%. The results
      suggest that, in combination with understanding and modeling of transient
      physiological differences between the subcutaneous and the blood glucose
      concentrations, it will be possible to calibrate by one-point in vivo calibration
      subcutaneously implanted sensors, even while the glucose concentration changes
      rapidly.

PMID- 9608853
TI  - Models for the length distributions of actin filaments: I. Simple polymerization
      and fragmentation.
AB  - We studied mathematical models for the length distributions of actin filaments
      under the effects of polymerization/depolymerization, and fragmentation. In this
      paper, we emphasize the effects of these two processes acting alone. In this
      case, simple discrete and continuous models can be derived and solved explicitly
      (in several special cases), making the problem interesting from a modeling and
      pedagogical point of view. In a companion paper (Ermentrout and Edelstein-Keshet,
      1998, Bull. Math. Biol. 60, 477-503) we investigate what happens when the
      processes act together, with particular attention to fragmentation by gelsolin,
      and with a greater level of biological detail.

PMID- 9608854
TI  - Models for the length distributions of actin filaments: II. Polymerization and
      fragmentation by gelsolin acting together.
AB  - In a previous paper, we studied elementary models for polymerization,
      depolymerization, and fragmentation of actin filaments (Edelstein-Keshet and
      Ermentrout, 1988, Bull. Math. Biol. 60, 449-475). When these processes act
      together, more complicated dynamics occur. We concentrate on a particular case
      study, using the actin-fragmenting protein gelsolin. A set of biological
      parameter values (drawn from the experimental literature) is used in computer
      simulations of the kinetics of gelsolin-mediated actin filament fragmentation.

PMID- 9608855
TI  - In vivo simulation of human pharmacokinetics in the rabbit.
AB  - The evaluation of drugs in vivo is often based on experimental models using small
      animals such as mice, rats and rabbits. However, these models could be improved
      to correspond more closely to the human situation if the pharmacokinetics of the
      drugs tested in animals were similar to that observed in humans. The use of a
      computer-controlled pump allowing an adequate flow of tobramycin and amikacin to
      be infused into rabbits enabled us to simulate the human pharmacokinetics of
      these antibiotics in vivo in this study. The function defining the rate of
      infusion required to perform the simulation of an intravenous bolus was first
      determined generally and symbolically for linear pharmacokinetic models
      independently from the number of compartments involved. The practical simulation
      of a decreasing monoexponential serum profile with a half-life of 2 h (one
      compartment model for the human pharmacokinetics of aminoglycosides) was then
      studied for tobramycin and amikacin on the basis of a two-compartment model in
      the animal. The kinetics obtained had an apparent elimination half-life of 1.97
      and 1.86 h, respectively. Linearity of the semilogarithmic regressions of the
      profiles obtained was quite sound. Finally, an a posteriori analysis of the
      pharmacokinetic model and its parameters is proposed on the basis of the results
      obtained after simulation.

PMID- 9608856
TI  - Modelling the spread of phocine distemper virus among harbour seals.
AB  - Data presented in earlier publications on the 1988 epizootic among seals in North
      West Europe show a pattern that is somewhat inconsistent with the predictions of
      the standard mathematical model of epidemics. We argue that for animals living in
      herds or colonies, such as seals, the mutual contact behaviour is such that
      models for the transmission of infectious diseases should be applied with special
      care for the distinction between numbers and densities. This is demonstrated by
      using a mechanistic description of the contacts among seals, which leads to a
      slightly different formulation of the model. Results of the analysis of this
      formulation are more in line with the data. The model introduced here can be
      applied to epidemics among all kinds of animals living in herds and in fact to
      any species with constant local density, independent of the total population size
      (i.e., occupying a variable area). Application of the traditional formulation,
      using different parameters for herds of different sizes, will give equally good
      results for non-lethal diseases. However, especially for diseases with a low R0
      and high death rates, such as the phocine distemper virus (PDV) disease, the two
      model formulations give quite different results. Further analysis of the model is
      performed to determine the most important factors influencing such an epidemic.
      The survival of infected animals turns out to have a disproportionately great
      influence on the intensity of the epidemic. Therefore in the case of the PDV
      epizootic we conclude that marine pollution may not only have contributed to the
      high death rates, but, if so, it has intensified the epizootic as well.

PMID- 9608857
TI  - Review of alternative methods of carcinogenicity testing and evaluation of human
      pharmaceuticals.
AB  - Hundreds of pharmaceuticals have been reported to give a positive result in the
      standard "Chronic Bioassay", which consists of an 18 to 24 month daily
      administration of the test compound in mice and rats. This is in contrast with 20
      pharmaceuticals, which are known to be carcinogenic to humans. The high incidence
      of apparently false-positive results in the Chronic Bioassay may be related to
      differences in mechanism of pharmacological action between rodents and humans,
      but also to the very high dose levels that have to be administered to rodents in
      accordance to regulatory guidelines. Lack of relevance to man therefore often has
      to be demonstrated by additional mechanistic studies. Based upon the deficiencies
      of the Chronic Bioassay and on the increased knowledge on cellular and molecular
      mechanisms involved in carcinogenicity, extensive discussions have recently taken
      place between regulatory agencies and industry associations at the occasion of
      International Conferences on Harmonization (ICH). These discussions have resulted
      in the possibility to use alternative short-to-medium-term carcinogenicity models
      in combination with a single two-year carcinogenicity study for evaluation of
      carcinogenicity. A description of these models is provided in this review as well
      as possible strategies for carcinogenicity testing and evaluation in the future.

PMID- 9608858
TI  - Metabolic consequences of alcohol dependency.
AB  - Alcohol dependency leads to a variety of biochemical adaptations and
      morphological changes which may be considered as either adaptive or destructive.
      This ranges from the utilization of ethanol as a metabolic fuel, to overt tissue
      and cellular damage, and may lead to increases in morbidity and mortality.
      Virtually every organ system is affected by either acute and chronic ethanol
      exposure and numerous metabolic pathways are altered. As a consequence of these
      wide ranging effects, it is extremely difficult to cover every aspect of alcohol
      toxicity in a single review. Instead, attention is focussed on selected areas,
      such as nutrition and protein metabolism in the liver and bone (and to a lesser
      extent, skeletal muscle and the gastrointestinal tract). The aim is to illustrate
      the numerous ways in which alcohol affects the body.

PMID- 9608859
TI  - [Primary tumors of the kidney in adults].

PMID- 9608860
TI  - [Prognostic value of Furhman's grade in renal cell carcinoma. A study of 170
      cases].
AB  - In order to evaluate the prognostic value of the anatomical stage (pTNM 1992) and
      of the histological factors (Fuhrman's grade, cellular and architectural types),
      170 renal cell carcinoma diagnosed between 1971 and 1991 were reviewed. In
      univariate analysis, the prognosis was correlated with the anatomical stage and
      Fuhrman's grade: for the 125 patients without metastasis, grades 1 and 2 had a
      good prognosis, whereas grades 3 and 4 did poorly. The cellular type was not
      related to survival. Among architectural types, only the pseudo-sarcomatous type
      was correlated with prognosis. Multivariate analysis revealed that grade and
      metastasis at diagnosis were two independent predictors of survival; the grade
      was prognostically superior to metastasis. Fuhrman's grade is essential in
      determining prognosis; its statistical value is superior to anatomical stage in
      multivariate analysis.

PMID- 9608861
TI  - [Prognostic value of E-cadherin expression in hepatocellular carcinoma].
AB  - Expression of E-cadherin (E-cad) was investigated immunohistologically in 91
      cases of operated hepatocellular carcinomas. An alteration of E-cad
      immunodetection was found in 56% of tumours. These alterations were correlated
      with histopathologic features of prognostic value including tumour size (> 3 cm),
      high nuclear grade and mitotic index. Patients with down-regulated E-cad
      expression had statistically significant shorter survival than the others.
      Although E-cad immunodetection was an independent prognostic factor, the Cox
      multivariate analysis showed that its prognostic value was low when compared to
      other prognostic factors.

PMID- 9608862
TI  - [Cytokeratins 7 and 20: aid in tumor typing].

PMID- 9608863
TI  - [Microdissection on histologic and cytologic preparation: an approach to tissue
      heterogeneity].

PMID- 9608864
TI  - Metanephric adenoma of the kidney. A clinicopathologic, immunohistochemical and
      electron microscopic study of two cases.
AB  - We report two cases of metanephric adenoma in 40 and 48 year-old women. These
      rare kidney tumors were composed of cuboidal epithelial cells forming tubules,
      glomeruloid structures and sheets. Ultrastructural and immunohistochemical
      studies revealed that the tumor cells are similar to epithelial cells of
      developing nephrons. These features differentiate the metanephric adenoma from
      tubulo-papillary renal carcinoma, nephroblastoma, and cortical adenoma. According
      to its invariably benign course, the metanephric adenoma treatment could be
      restricted to a simple tumorectomy.

PMID- 9608865
TI  - [Congenital hepatic fibrosis. Five cases with late occurrence in adults].
AB  - Congenital hepatic fibrosis (CHF), is an autosomal recessive disease, presenting
      principally in childhood with portal hypertension and/or cholangitis, and often
      associated with renal malformations. The forms presenting later in adults are
      rare, and illustrated herein by 4 cases with dominant cholangitis, and one latent
      form. Biological tests and radiological imaging are often normal. The
      histopathologic diagnosis, sometimes difficult on liver needle biopsy is based on
      fibrous enlargement of portal areas, with numerous and tortuous bile ducts, lined
      by regular, cuboidal epithelium. Interportal fibrosis can mimic cirrhosis. In
      CHF, cholangitis are favoured by intrahepatic biliary dilatation, sometimes
      related to Caroli's disease, associated in 25% of cases. Suppurative
      complications, sometimes fatal explain the severity of cholangitis forms of CHF,
      contraindicating inopportune cholangiography and biliary surgery.

PMID- 9608866
TI  - [Breast metastasis from a "tall cell variant" of papillary thyroid carcinoma].
AB  - The authors report a case of breast metastasis from a "tall cell" variant of
      papillary thyroid carcinoma in a 59-year-old woman. This metastasis was
      discovered two months after the diagnosis of an inextirpable thyroid tumor. Tall
      cell variant of papillary thyroid carcinoma is a sub-type of papillary carcinoma
      with an aggressive course and frequent metastases (in patients over 50 years of
      age). No mammary metastasis of this tumor type has been reported so far.

PMID- 9608867
TI  - [Endometrial stromal tumor associated with rhabdoid phenotype and and zones of
      "sex cord-like" differentiation].
AB  - An unusual endometrial stromal sarcoma is described in a 50-year-old patient. The
      distinctive feature of this case is the focal occurrence of sex cord-like pattern
      and rhabdoid appearance of tumor cells. Rhabdoid cells have an eosinophilic
      cytoplasm and a vesicular nucleus with a prominent nucleolus.
      Immunohistochemistry showed positive cytoplasmic staining for both cytokeratin
      and vimentin, and ultrastructural examination identified tumor cells with
      abundant cytoplasmic intermediate filaments. To our knowledge, only one case of
      endometrial stromal sarcoma with this unusual morphological association has been
      reported in the literature.

PMID- 9608868
TI  - [Pseudomyxoma extraperitonei. Report of 3 cases].
AB  - The authors report three additional cases of pseudomyxoma extraperitonei and
      describe the modalities of occurrence and evolution. Pseudomyxoma extraperitonei
      arises from spontaneous or accidental implantation of mucosal cells of the
      primary site. This inoculation is accompanied by the modification of glandular
      cells which survive by adapting themselves to the interstitial connective tissue
      environment, raising thus the ability of extensive involvement and tumor-like
      invasive behavior.

PMID- 9608869
TI  - [A voluminous inguinal hernia].

PMID- 9608870
TI  - [A mesenteric lymph node suspected of lymphoma].

PMID- 9608871
TI  - [A resistant keratitis].

PMID- 9608872
TI  - [Cystic kidney tumor in a woman].

PMID- 9608873
TI  - [Fetal neuropathology].

PMID- 9608874
TI  - [An unusual nodule of the thyroid].

PMID- 9608875
TI  - Synthesis and pharmacological evaluation of a new homologous series of (+/-)-p
      fluoro-phenyl alcohol amide anticonvulsants.
AB  - The anticonvulsant activity of a homologous series of (+/-)-p-fluoro-phenyl
      alcohol amides is described. The compounds (+/-)-2-hydroxy-2-(4'
      fluorophenyl)butyramide (2), (+/-)-3-hydroxy-3-(4'-fluorophenyl)pentanamide (4)
      and (+/-)-4-hydroxy-4-(4'-fluorophenyl)hexanamide (6) were prepared and tested.
      Compounds 2, 4 and 6 exhibited a similar significant activity in seizures
      provoked by pentylenetetrazol. Incorporation of fluorine in the para position of
      the phenyl ring, increased both their potency at the time of the peak drug effect
      and the duration of their anticonvulsant activity.

PMID- 9608876
TI  - Effects of taltirelin hydrate (TA-0910), a novel thyrotropin-releasing hormone
      analog, on in vivo dopamine release and turnover in rat brain.
AB  - Effects of taltirelin hydrate (CAS 103300-74-9, TA-0910), a novel thyrotropin
      releasing hormone (TRH) analog, on the cerebral monoamine systems, especially the
      release and turnover of dopamine (DA) in rat brain were compared with those of
      TRH by intraperitoneal administration. Taltirelin hydrate (1-10 mg/kg) increased
      the extracellular levels of DA and its metabolites, 3,4-dihydroxyphenylacetic
      acid (DOPAC) and homovanillic acid (HVA) in the nucleus accumbens and corpus
      striatum for 3 h in a microdialysis study. TRH (30 mg/kg) also increased the
      levels of these substances, the potency of TRH being the same as that of
      taltirelin hydrate at doses of 1-3 mg/kg. Taltirelin hydrate (10 mg/kg) also
      caused an increase in 3-methoxytyramine (3-MT: DA metabolite) until 6 h after the
      treatment and L-3-dihydroxyphenylalanine (DOPA: precursor of DA and
      noradrenaline). Taltirelin hydrate also increased the 3-methoxy-4
      hydroxyphenylglycol (MHPG: noradrenaline metabolite) level in the frontal cortex
      and hypothalamus, and 5-hydroxytryptophan (5-HTP: serotonin precursor)
      accumulation and 5-hydroxyindoleacetic acid (5-HIAA: serotonin metabolite) level
      in the nucleus accumbens or corpus striatum. These results suggest that
      taltirelin hydrate possesses not only an enhancing effect on DA release, but also
      a stimulating effect on the monoamine system. Moreover, these actions were 10-30
      times stronger and also longer-lasting than those of TRH. In addition, the
      mechanisms of DA release induced by these drugs were different from those induced
      by methamphetamine.

PMID- 9608877
TI  - Protective effects of taurine against reperfusion-induced arrhythmias in isolated
      ischemic rat heart.
AB  - The protective effect of taurine (CAS 107-35-7) against reperfusion-induced
      arrhythmias has been investigated in isolated perfused rat heart (Langendorff
      method). Partial ischemia was induced by occlusion of left descending artery for
      15 min, followed by 10 min reperfusion. Left ventricular pressure and epicardial
      ECG were continuously monitored before and during ischemia and reperfusion. A
      control group was submitted to partial ischemia without taurine treatment. Three
      groups were submitted to partial ischemia, under taurine (10 mmol/l) treatment in
      the Krebs-Henseleit perfusing buffer during ischemia only (group 1), at
      reperfusion (group 2) and throughout the experimental period (group 3).
      Malondialdehyde levels were measured as an index of lipid peroxidation and heart
      muscle damage. The incidence of irreversible ventricular fibrillation was
      significantly diminished from 83% (control group) to 36% in group 1, 42% in group
      2 and 16% in group 3. The incidence of premature ventricular beats and
      ventricular tachycardia at reperfusion as well as malondialdehyde levels were
      significantly decreased under taurine treatment. The results indicate that
      taurine protects ischemic heart against reperfusion-induced arrhythmias, via both
      its properties as membrane stabilizer and oxygen free radical scavenger.

PMID- 9608878
TI  - Preclinical safety studies of the combination moexipril
      hydrochloride/hydrochlorothiazide.
AB  - The general pharmacological properties of a combination of the angiotensin
      converting enzyme (ACE) inhibitor moexipril hydrochloride (CAS 82586-52-5) and
      the thiazide diuretic hydrochlorothiazide (CAS 58-93-5, HCTZ), ratio 7.5 + 12.5,
      were studied in generally accepted models in vitro and in vivo. In vitro, the
      combination showed neither agonistic nor antagonistic activities on the isolated
      guinea pig trachea in concentrations up to 2 x 10(-4) g/ml. In mice, there was no
      effect on intestinal motility or the thiopental-induced sleeping time up to 1000
      mg/kg. The only activity observed in mice was an inhibition of spontaneous
      motility after oral dosing with 300 and 1000 mg/kg, respectively. Both HCTZ (1-10
      mg/kg) alone and the combination moexipril/HCTZ (1.6 or 4.8 mg/kg) produced dose
      related increases in diuresis and electrolyte excretion in rats, however, without
      any potentiating effects for the drug combination. On the cardiovascular system
      of anaesthetised dogs, the effects observed were as expected, e.g. dose-related
      decrease in blood pressure. Repeated dose toxicity studies in rats and dogs
      revealed the kidney as target organ. This effect, based on highly exaggerated
      pharmacological activity, is well-known for other ACE inhibitors. No potential
      for teratogenic effects could be observed for the drug combination. In summary,
      the preclinical data indicate that the combination of moexipril and HCTZ (ratio
      7.5 + 12.5) represents a safe drug without relevant side effects or gross
      toxicity.

PMID- 9608879
TI  - Pharmacokinetics, protein binding and metabolic profile of 3H-icometasone
      enbutate following intravenous, oral and intratracheal administrations to Sprague
      Dawley rats.
AB  - Absorption, distribution and excretion of 3H-icometasone enbutate (9 alpha-chloro
      11 beta,17 alpha,21-trihydroxy-16 alpha-methylpregna-1,4-diene-3,20-dione, 17
      butyrate, 21-acetate, CAS 103466-73-5 CL09) were studied in male and female
      Sprague-Dawley rats after a single dose administration by intravenous (1 mg/kg),
      oral and intratracheal (2 mg/kg) routes. The metabolic profile after the
      different routes and protein binding were also determined. Independent of the
      route, the radioactivity was mainly excreted in faeces. Less than 10% of the dose
      were excreted in urine. The majority of the administered doses was recovered
      within 24 h postdose, and the total recovery of the doses administered was
      obtained. After oral and intravenous administration to bile-duct cannulated rats,
      most of the radioactivity was excreted in the bile (80% of the administered dose)
      and some radioactivity was found in the faeces. It can thus be concluded that
      some intestinal secretion occurred. After oral administration, mean maximum blood
      concentrations were obtained about 0.75 h postdose. For the intratracheal route,
      the radioactive dose administered was too low to determine precise blood
      pharmacokinetic parameters. However, the distribution study results allowed us to
      conclude that the drug was absorbed first from the lungs and then from the
      gastrointestinal tract. Immediately after the intravenous injection, the liver,
      the kidneys, the small intestine and its contents and the carcass presented the
      highest levels of radioactivity. 168 h postdose, low radioactivity was still
      measurable in these organs. In other tissues, the radioactivity decreased
      reaching the limit of quantification 72 h postdose. After oral administration,
      the maximum concentrations were observed 1 h after administration in the liver,
      the small intestine and its contents. Then the radioactivity decreased in most of
      the tissues but a slight increase at 72 and/or 120 h postdose was noted in large
      intestine contents, carcass, lungs, eyes. After intratracheal administration, the
      maximum radioactivity was observed in lungs and trachea. A few minutes later the
      radioactivity reached the gastrointestinal tract. The protein binding study
      showed a saturable binding in rat and human plasma without notable differences
      between the two species. The binding on human serum albumin was shown to be non
      saturable with a total binding capacity of 7.48 +/- 1.83 mumol/l, suggesting that
      other proteins were involved in CL09 binding. This binding was demonstrated to be
      reversible. CL09 was extensively metabolized since no unchanged CL09 was
      recovered in bile or urine and at least nine metabolites have been detected. The
      profiles seemed to be different according to the route of administration.

PMID- 9608880
TI  - Dose-dependent protection by azelastine eye drops against pollen-induced allergic
      conjunctivitis. A double-blind, placebo-controlled study.
AB  - The efficacy and tolerability of azelastine (CAS 58581-89-8) eye drops at three
      different doses (0.025%, 0.05% and 0.1%) were investigated in a double-blind,
      randomized, placebo-controlled, crossover study in 24 subjects with a history of
      allergic conjunctivitis/rhinoconjunctivitis, who were challenged, out of season,
      by airbone allergen in the "Vienna Challenge Chamber" (VCC). Subjects received a
      single dose of azelastine eye drops 60 min before the start of a 4 h challenge in
      the VCC. Additional local challenge, mimicking a gust of wind, was administered
      15 min before the end of the session. Each of the 4 study days was separated by a
      2 week washout period. Azelastine eye drops showed a dose-dependent inhibition of
      the development of itching of the eyes. The effect was most pronounced 15 min
      after the additional local challenge. A maximal effect was achieved at a dose of
      0.05%. Similar effects were observed on lacrimation. Azelastine eye drops also
      dose-dependently inhibited the degree of conjunctival redness, measured by
      digital imaging, and tended to reduce the low incidence of chemosis observed.
      Ranking of the results of all symptoms for each treatment group confirmed the
      optimal effect at a dose of 0.05%. Azelastine eye drops had no effect on nasal
      and bronchial symptoms or on measurements of airways function (FEV1). No adverse
      effects of the treatments were reported. The data support the use of 0.05%
      azelastine eye drops in the treatment of allergic
      conjunctivitis/rhinoconjunctivitis.

PMID- 9608881
TI  - Anti-inflammatory activity of inhaled mometasone furoate in allergic mice.
AB  - Mometasone furoate (CAS 83919-23-7, Sch 32088) is a new inhaled corticosteroid
      that is being developed to treat allergic inflammatory airway disorders such as
      rhinitis and asthma. In this study, we investigated the effects of inhaled
      mometasone furoate in allergic mice that, after antigen challenge, develop an
      influx of eosinophils and T cells and display an increased mRNA expression of
      proinflammatory cytokines in the lungs. Mometasone furoate aerosol was generated
      from metered dose inhalers and delivered into an animal exposure chamber. The
      mice were exposed to mometasone furoate by nose-only inhalation at respired doses
      ranging from 0.5-33 micrograms/kg given 24, 18 and 2 h before aeroallergen
      challenge. The elevated eosinophil numbers in the bronchoalveolar lavage fluid
      and lung tissues of sensitized, ovalbumin challenged mice were dose-dependently
      inhibited by inhaled mometasone furoate. Increased numbers of Thy1+ T cells and
      CD4+ (T-helper) and CD8+ (T-cytotoxic) T cell subsets were seen in the
      bronchoalveolar lavage fluid of ovalbumin-challenged mice. Pretreatment of these
      animals with mometasone furoate (33 micrograms/kg) reduced the number of Thy1+ T
      cells and the T-helper subset. Furthermore, mometasone furoate (33 micrograms/kg)
      reduced the percentage of CD44+ T-helper cells (activated/memory cells) to the
      levels observed in non-sensitized, ovalbumin-challenged mice. There were
      increased levels of steady-state mRNA for interleukin-4, interleukin-5, and to a
      lesser extent, gamma-interferon in the lungs of sensitized mice after ovalbumin
      challenge and pretreatment with mometasone furoate reduced the steady-state mRNA
      levels of these cytokines. Our results demonstrate a potent lung anti
      inflammatory effect of inhaled mometasone furoate and identify that inhibition of
      T cell influx, eosinophil accumulation and modulation of cytokine activity are
      important components of this response.

PMID- 9608882
TI  - Comparative bioavailability study of two oral formulations of ibuprofen.
AB  - The pharmacokinetic profile of ibuprofen (CAS 15687-27-1) in a Fast Melting
      Tablet (FMT), a modified release formulation (encapsulation of the active
      ingredient in gastroresistant microcapsules), was compared with that of sugar
      coated tablets (SCT; Moment 200). In the following paper an open, single dose,
      cross-over study in eighteen healthy volunteers (9 males and 9 females--mean age
      27 years) is reported. The results of the study demonstrated that the rate of
      absorption of the FMT was markedly slower than that of the SCT. In fact, the
      geometric mean peak plasma concentration (Cmax) and median peak time (tmax) were
      12.04 micrograms/ml at 3.5 h with the new formulation, and 18.71 micrograms/ml at
      1 h with the SCT, respectively. The longer absorption time and diminished peak
      plasma concentration did not affect the extent of absorption of the two
      formulations, expressed by AUCo-t and AUC (90% confidence interval: 0.89-1.00 for
      AUCo-t and 0.92-1.03 for AUC). The safety profile of both drugs proved to be very
      good and no clinically significant adverse events were observed.

PMID- 9608883
TI  - Apolipoprotein E*3-Leiden transgenic mice as a test model for hypolipidaemic
      drugs.
AB  - Apolipoprotein (APO) E*3-Leiden mice with impaired chylomicron and VLDL (very low
      density lipoprotein) remnant metabolism display hyperlipidaemia and
      atherosclerosis. In the present study, these mice were used for testing the
      hypolipidaemic effect of two marketed agents, lovastatin (CAS 75330-75-5) and
      gemfibrozil (CAS 25812-30-0) as well as a novel compound, SB 204990 (the 5-ring
      lactone of +/-(3R*,5S*) 3-carboxy-11-(2,4-dichlorophenyl)-3,5-dihydroxyundecanoic
      acid, CAS 154566-12-8), a potent inhibitor of cholesterol and fatty acid
      synthesis at the level of ATP-citrate lyase. APOE*3-Leiden mice were fed a
      saturated fat and cholesterol-rich diet supplemented with either 0.05 or 0.1% w/w
      of lovastatin, 0.1 or 0.2% w/w of gemfibrozil or 0.1 or 0.2% w/w of SB 204990.
      Lovastatin showed a dose-related decrease in plasma cholesterol levels (up to 
      20%) due to a lowering of LDL and HDL (low density resp. high density
      lipoprotein)-cholesterol (-20 and -18%, respectively), while plasma triglyceride
      levels were unaffected. Gemfibrozil had no effect on plasma total cholesterol
      levels but gave significant dose-dependent decreases in plasma (VLDL)
      triglyceride levels (up to -53%). SB 204990 resulted in a dose-dependent
      reduction of plasma cholesterol (up to -29%) by lowering VLDL, LDL and HDL
      cholesterol (-50, -20 and -20%, respectively). In addition, a strong dose
      dependent reduction of plasma (VLDL) triglycerides up to -43% was observed with
      this compound. Although the effects of gemfibrozil and SB 204990 were not simply
      explained by changes in a single determinant of VLDL metabolism--no effects of
      these drugs were seen on post-heparin plasma lipoprotein lipase activity, in vivo
      rate of VLDL synthesis or hepatic apoC-III mRNA levels--APOE*3-Leiden mice were
      found to give robust hypolipidaemic responses to these test compounds. The
      responsiveness to hypolipidaemic therapy combined with a clear relationship
      between aortic lesion size and plasma cholesterol exposure, as demonstrated
      previously, makes this mouse an attractive model for the testing of anti
      atherosclerotic properties of hypolipidaemic drugs.

PMID- 9608884
TI  - Effects of YF476, a potent and selective gastrin/cholecystokinin-B receptor
      antagonist, on gastric acid secretion in beagle dogs with gastric fistula.
AB  - The antisecretory effects of the gastrin/cholecystokinin-B (CCK-B) receptor
      antagonist YF476 ((R)-1-[2,3-dihydro-2-oxo-1-pivaloylmethyl-5-(2'-pyridyl) 1H-1,4
      benzodiazepin-3-yl]-3-(3-methylaminophenyl)-urea, CAS 155488-25-8) on
      secretagogue- and peptone-induced gastric acid secretion in beagle dogs with
      chronic gastric fistula were examined. Plasma gastrin concentrations were
      evaluated following introduction of peptone into the stomach. Intravenous
      administration of YF476 dose-dependently inhibited pentagastrin (1
      microgram/kg/h)-induced gastric acid secretion, with an ED50 value of 0.0023
      mumol/kg. In contrast, intravenous administration of YF476 (0.3 mumol/kg) did not
      affect histamine (15 micrograms/kg/ h)-induced gastric acid secretion. Oral
      administration of YF476, famotidine and omeprazole dose-dependently inhibited
      peptone (8%, 200 ml)-induced gastric acid secretion with ED50 values of 0.11,
      0.76 and 4.28 mumol/kg, respectively. The antisecretory effect of YF476 was about
      7 and 40 times more potent than that of famotidine and omeprazole, respectively.
      Plasma gastrin concentrations were increased by introduction of peptone. These
      results suggest that YF476 is an extremely potent and selective antisecretory
      drug and the endogenous gastrin plays an important role in peptone-induced
      gastric acid secretion in dogs.

PMID- 9608885
TI  - Uptake of ethylenediamine tetramethylene phosphonic acid in normal bone after
      multiple applications. A non-human primate study.
AB  - Palliation of bone pain in patients with bone metastases has previously been
      evaluated using 153Sm (samarium) complexed to bone seeking ethylenediamine
      tetramethylene phosphonic acid (CAS 1429-50-1, EDTMP). Repeated application of
      the radioligand as needed was found progressively less effective. This study
      questions whether EDTMP exerts a blocking function, limiting access to bone or
      osseous tumours with successive administration. The pharmacokinetics and
      biodistribution of 153Sm-EDTMP in the normal experimental baboon (n = 6) during
      three successive applications (6 weekly) each with two different concentrations
      of EDTMP (0.7 and 1.4 mg/kg b.wt.) were investigated using bone scintigraphy.
      153Sm-EDTMP (111 MBq) was injected in each case and monitored for 5 h. Curves of
      tracer kinetics and bone to background uptake were obtained, also blood and
      cumulative urine curves. Comparisons were statistically assessed in each group
      between successive applications and between EDTMP concentrations. Partial
      blocking with the low EDTMP concentration reached statistical significance after
      the third application. The first application of the high EDTMP concentration
      yielded lower uptake in the bone than did low EDTMP pointing to blocking by the
      high concentration, but not seen with repeated applications. Continual
      application of high concentration EDTMP could lead to a reduced level of calcium
      in serum and increased parathyroid hormone levels which might trigger
      osteoblastic activity and bone remodelling. This would partially affect the
      blocking which was thus more obvious at the low EDTMP concentration.

PMID- 9608886
TI  - Innovative and economic potential of mammalian cell culture.
AB  - Innovations for economic optimization of manufacturing processes of mammalian
      cell culture processes address new expression systems, optimized cell culture
      media and feeding systems, economy of scale, efficient harvest systems for viable
      cell separation, redesign of downstream processing and reduction of the overall
      number of quality control assays. A very efficient expression system in Chinese
      hamster ovary cells is the NEOSPLA expression system yielding 60-100 micrograms
      monoclonal antibodies per cell and day. Efficient supplements in nutrient feeding
      are insulin and amino acids which contribute to a high extent to the productivity
      of the mammalian cell culture process. Large scale manufacturing processes lower
      cost of goods by reduction of turn around cost for cleaning and steaming in
      place, media preparation, number of batches for annual campaign, in-process and
      quality control. In downstream processing the number of process steps and the
      step yield are responsible for the economics. Process control systems in a
      computer assisted manufacturing plant increase success rate, reduces man power
      and minimizes shifts. In the innovative process also alternative technologies
      such as transgenic animals should be considered to improve the economy of the
      manufacturing processes.

PMID- 9608887
TI  - Health services research, outcomes, and perinatal information systems.
AB  - The progress in information and communication technology, together with the
      search for the most effective and efficient ways to use the limited resources for
      health care, are opening new areas for research and development in perinatal
      care. Information systems and practice oriented by evidence-based medicine are
      modifying the operation of health services, and the quality of their management
      is being monitored by the success of their outcomes. As a study case, a Perinatal
      Information System widely used in Latin America and the Caribbean is discussed in
      some detail. Future challenges in the compatibility of information systems and
      databanks, the need for longer follow-up periods and measurement of health
      related quality of life as outcomes for perinatal care, and the strategies to
      integrate all these concepts for the improvement of daily practice are discussed.

PMID- 9608888
TI  - Necrotizing enterocolitis.
AB  - Necrotizing enterocolitis is a relatively common disorder of unknown etiology
      that primarily affects premature newborns. The majority of babies with
      necrotizing enterocolitis respond to nonsurgical management, and, despite an
      increase in the number of premature infants, the surgical mortality rate has
      improved. This review provides an overview of the current literature covering new
      developments in etiology, risk factors, pathogenesis, diagnosis, therapy,
      outcome, and preventable measures related to necrotizing enterocolitis.

PMID- 9608889
TI  - Magnesium sulfate and cerebral palsy in premature infants.
AB  - This article reviews clinical and experimental evidence as to whether magnesium
      sulfate, administered soon before premature birth, can reduce the high rate of
      cerebral palsy in tiny infants. Three observational studies have reported an
      association of magnesium sulfate with lower rate of cerebral palsy, whether
      treatment was for maternal preeclampsia or for tocolysis. One of these studies
      also noted a significant reduction in cognitive disability. In another study, no
      significant protective effect was seen except in a small subset of infants.
      Magnesium was neuroprotective in many but not all of a variety of experimental
      studies and has a variety of biologic effects that might account for benefit. All
      existing clinical studies had relatively small numbers of very premature infants.
      Although all attempted to control for possible confounders, such studies cannot
      provide definitive answers as to possible benefits or risks of magnesium therapy.
      Only randomized clinical trials are likely to resolve the question of whether a
      brief exposure to an agent which, in the American experience, is considered safe
      if administered with appropriate supervision, can reduce longterm neurologic
      disability in premature infants.

PMID- 9608890
TI  - Developmental care in the newborn intensive care unit.
AB  - Developmental care is a framework that encompasses all care procedures as well as
      social and physical aspects in the newborn intensive care unit. Its goal is to
      support each individual infant to be as stable, well-organized, and competent as
      possible. The infant's physiologic and behavioral expression of current
      functioning is seen as the reliably available guide for caregivers to estimate
      the infant's current strengths, vulnerabilities, and thresholds to
      disorganization; to identify the infant's own strategies and efforts in
      collaborating toward best progress; and to implement care in a way that enhances
      the infant's stability and competence. The family is understood to be the
      infant's primary coregulator. It is the caregivers' responsibility to maximize
      opportunities to enhance each infant's and family's strengths and reduce apparent
      stressors. Studies of the effectiveness of developmental care also identify
      implications for staff education and challenges for nursery-wide implementation.

PMID- 9608891
TI  - Mother-to-child transmission of HIV.
AB  - The first children with HIV-1 infection were described in 1983. As of 1998, the
      global HIV epidemic is having a profound impact on the health and survival of
      children. Almost all HIV infections among young children are due to vertical
      transmission, and the intrapartum period appears to provide us with a crucial
      window of opportunity for prevention. Postnatal transmission through
      breastfeeding also contributes an estimated one third to one half of vertical
      transmission worldwide. Carefully conducted epidemiologic studies are elucidating
      the immunologic, virologic, and behavioral factors affecting the risk of HIV-1
      transmission from mother to infant and the natural history of HIV disease in
      perinatally infected children. Transmission of HIV-1 is influenced by many
      factors, and a high maternal viral load is insufficient to fully explain vertical
      transmission of HIV-1. Pediatricians and other providers should counsel HIV
      infected women about the means available to decrease the risk of HIV transmission
      to the infant. However, the majority of HIV-infected children are born in the
      developing world, and a crucial challenge is to identify safe and effective
      interventions that are feasible in those countries with the most significant HIV
      burden.

PMID- 9608892
TI  - The neonatal nurse practitioner.
AB  - Neonatal nurse practitioners have been introduced into tertiary level neonatal
      intensive care units in the United States, Canada, and the United Kingdom in
      response to the increased survival rates of extremely low birth weight infants,
      the short-age of physicians, and the nursing profession's emphasis on development
      of advanced nursing practice roles. This brief review summarizes the recent
      research related to the facilitating and constraining factors that influence the
      role; the safety, effectiveness, and cost of the role; the impact of this role on
      other members of the health care team; and the satisfaction of those in the role.

PMID- 9608893
TI  - Hypernatremia in infancy.

PMID- 9608894
TI  - An overview of renal trauma.
AB  - The topic of renal trauma has offered many substantial and poignant issues of
      debate over the years, such as classification schemes, management techniques,
      imaging and diagnostic preferences, and post-traumatic sequelae. This overview
      presents the most recent and applicable arguments and data surrounding the
      treatment of renal trauma. Various classification structures have been proposed
      and utilized for over a century, yet they do not all focus on the different
      features of trauma presentation (pathogenesis, morphologic implications,
      symptoms, predisposing conditions) in an equal manner. The traditional
      controversy between observation and invasive surgery with trauma patients still
      exists, yet new methods of treatment protocol have been proposed for patients in
      traumatic shock. Concerning the state of the patient, it has been recognized that
      children with pretraumatic renal abnormalities are more prone to serious injury,
      but it is still undecided whether renal trauma will predispose a child to later
      pathologies such as arterial hypertension. Modern advances in imaging, and
      diagnostic procedures have dramatically shifted the reliance on intravenous
      pyelograms to computed tomography, yet the question remains of how much imaging
      actually is needed in the average patient presenting with renal trauma. Pertinent
      issues such as these are presented, with main emphasis on literature published
      within the past 18 months.

PMID- 9608895
TI  - Nocturnal enuresis in children.
AB  - Nocturnal enuresis (NE) can result from an interaction of unstable detrusor
      contractions, delayed arousal from sleep, and nocturnal polyuria. Some children
      with NE can hold urine well for several hours during the day and have isolated
      nocturnal enuresis, while others manifest diurnal voiding symptoms (DVS) as well,
      including urinary frequency, urgency, urge incontinence, and pelvic withholding.
      The pathogenesis of NE in patients with isolated NE may be different than in
      those with NE and DVS. In children with NE and DVS, detrusor instability may play
      a major role in the causation of their voiding problems, whereas delayed arousal
      from sleep in response to a full bladder may be a major contributor to NE in
      patients with isolated NE. The treatment should address the underlying pathogenic
      factors. The commonly used treatment regimens are described. Motivation and
      efforts of the child in training the bladder are vital to achieving cure of
      enuresis.

PMID- 9608896
TI  - Genetic renal disease.
AB  - Many genetic renal disease now have specific genetic definitions, allowing
      prognostication. Several glomerular basement membrane defects include Alport's
      syndrome and benign familial hematurias. Genetic tubular or interstitial
      structural defects likely include familial juvenile nephronophthisis, as well as
      the polycystic diseases. Hereditary metabolic diseases can result in storage
      processes and circulating lipid disorders, which result in progressive glomerular
      sclerosis. Hereditary metabolic errors result in products causing obstruction and
      interstitial damage. Other hereditary disorders cause hemodynamic process that
      result in renal damage. The vascular structural defects of Marfan syndrome,
      Alagille syndrome, neurofibromatosis, and Cockayne's syndrome can secondarily
      result in renal vascular destruction. An awareness of these hereditary disease
      pathways to renal disease is essential to primary care pediatrics.

PMID- 9608897
TI  - Causes, management approaches, and outcome of acute renal failure in children.
AB  - Although acute renal failure (ARF) remains an uncommon problem in pediatrics, it
      is characterized by significant morbidity and mortality. This review addresses
      several broad topics related to ARF and summarizes the results of recent studies
      of particular significance. Following a brief discussion of the main causes of
      ARF in children, more detailed attention is paid to the problems of ARF caused by
      hemolytic-uremic syndrome and of ARF in neonates. Management of ARF is reviewed,
      including recent advances in dialysis modalities. Recent data on the outcome of
      ARF in children are summarized, and future approaches to the prevention and
      management of ARF are briefly examined.

PMID- 9608898
TI  - Renal osteodystrophy.
AB  - Secondary hyperparathyroidism develops in most patients with chronic renal
      failure, and is associated with the histologic finding of osteitis fibrosa
      cystica. The disease is characterized by growth failure and severe bone
      deformities in children, especially the very young. The pathogenesis of renal
      osteodystrophy is related to phosphate retention, and its effect on calcium and
      calcitriol metabolism, in addition to roles played by metabolic acidosis,
      cytokines, and degradation of parathyroid hormone. Treatment includes restriction
      of dietary phosphorous intake, phosphate binders, and use of active metabolites
      of vitamin D.

PMID- 9608899
TI  - Urinary tract infection.
AB  - The approach to urinary tract infection remains a difficult and sometimes
      controversial issue. One area in particular is accurate diagnosis. In a recent
      article it was suggested utilizing the "enhanced" urinalysis, not as a
      replacement to culture but as a potential sensitive predictor to allow therapy to
      be given while awaiting culture results. Another difficult area is the issue of
      radiologic evaluation for underlying urologic abnormalities following a urinary
      tract infection. Previous discussion on this topic has pointed to early
      evaluation, even after the first urinary tract infection. There now seems to be
      some reconsideration of when to evaluate children following urinary tract
      infection. Some reviews, however point to a less aggressive approach. Another
      area of discussion is the evaluation of siblings of index cases with reflux. Here
      there is new data suggesting that evaluation of young siblings (under 6 years of
      age) may yield a relatively high incidence of reflux whereas evaluation of
      siblings over 6 years of age yields a small percentage of patients with reflux.
      The question of circumcision is another area of long-term interest in the study
      of urinary tract infections. Still more data published recently suggests that
      uncircumcised males have a higher incidence of urinary tract infection. However,
      this continues to be a point of controversy.

PMID- 9608900
TI  - Therapeutics and toxicology.

PMID- 9608901
TI  - Evidence-based pain management for infants.
AB  - The impact of pain on infants has been the topic of increasing research interest
      over the past decade. Although pain is now known to be stressful and the source
      of immediate and long term consequences, inadequate progress has been made in
      infant pain management. Research evidence provides the basis for effective pain
      management. However, the quality of the evidence, inconsistent findings, and the
      perceived lack of clinical relevance may have hindered the utilization of
      research on infant pain management in clinical practice. Reconceptualization of
      the definition of pain, increased methodologic rigor, validated assessment
      approaches, and systematic reviews of research studies on pain management may
      provide the opportunity for improved pain management using evidence-based
      practice.

PMID- 9608902
TI  - The genetic basis for variation in antibody response to vaccines.
AB  - Following a brief review of important concepts of vaccine response and vaccine
      immunology, recent reports on genetic determinants of vaccine response are
      reviewed. Recent data demonstrating significant associations with particular
      human leukocyte antigen genes and responsiveness to measles and hepatitis B
      vaccines are discussed, along with the influence of Km and Gm allotype genes on
      pneumococcal polysaccharide vaccines. These recent findings have important
      considerations for research, vaccine development, and clinical practice.

PMID- 9608903
TI  - Child abuse and sudden infant death syndrome.
AB  - Ann Botash reviews the current literature regarding the association of retinal
      hemorrhage and subarachnoid bleeds in infants who have suffered head trauma.
      Particular emphasis is placed on differentiating these findings from those in
      children who suffer other forms of trauma, especially cardiopulmonary
      resuscitation. The office practitioner needs appropriate skills in performing
      careful retinal examination and when to refer patients to an ophthalmologist for
      specific evaluation. The current literature on sudden infant death syndrome is
      reviewed in this section by Steven Blatt and Victoria Meguid. Specific studies
      about sleep position are analyzed and the rationale for the "back to sleep"
      movement is explained from a physiologic standpoint. The impact of maternal
      smoking and poor prenatal care is also reviewed in the form of a number of
      epidemiologic studies. It is important for the clinician to recognize that there
      is often a fine line differentiating sudden infant death syndrome and
      infanticide. The pediatrician needs to be aware of the importance of careful
      investigation of death scenes to insure that we are not missing other causes of
      death in those patients who are labeled as having died of sudden infant death
      syndrome.

PMID- 9608904
TI  - [Identification of mRNA, localized at various segments of the Xenopus laevis
      embryo at early stages of the gastrula].

PMID- 9608905
TI  - [Regeneration of irradiated, mechanically damaged rat skeletal muscle after
      exposure to infrared laser irradiation].

PMID- 9608906
TI  - [Is "work hypoxia" a stimulus for structural-metabolic changes in skeletal
      muscle?].

PMID- 9608907
TI  - [Syntagmatic and paradigmatic principles of organizing lexicon and functional
      asymmetry of the brain].

PMID- 9608908
TI  - [Search for molecular-genetic markers associated with arterial hypertension by
      polymerase chain reaction with random primers].

PMID- 9608909
TI  - [Ribonuclease gene--a base of "zero background" cloning].

PMID- 9608910
TI  - [Structural-conformational changes of DNA in open promoter complexes with E. coli
      RNA-polymerase].

PMID- 9608911
TI  - [The dnaK genes as a basis for phylogenetic analysis of Mycoplasma].

PMID- 9608912
TI  - [Types of cerebral hemisphere dominance and sound analysis].

PMID- 9608913
TI  - [Modeling of a temperature dependence of the efficacy of site-specific
      modification of nucleic acids by oligonucleotide reagents forming reactive
      intermediates. Discovery and prediction of novel characteristics of
      modification].

PMID- 9608914
TI  - [Anticholinesterase effect of calcium channel blockers: diltiazem, verapamil, and
      nifedipine].

PMID- 9608915
TI  - [Formation of reactive oxygen species in aqueous solutions after exposure to
      extremely-high frequency electromagnetic fields].

PMID- 9608916
TI  - [Plastic activity of muscle allotransplants after preliminary irradiation with
      helium-neon laser].

PMID- 9608917
TI  - [Phase shifts of gamma-oscillations and reciprocal inhibition in transcallosal
      interactions].

PMID- 9608918
TI  - [Evolution theory, mutations, and human life span].

PMID- 9608919
TI  - [Degradation of juvenile hormone does not play a role in the reproductive
      function of Drosophila melanogaster males].

PMID- 9608920
TI  - [Staphylokinase and its mutants: a new generation of thrombolytic agents].
AB  - Staphylokinase which is extracted from Staphylococci has been known for more than
      40 years as a profibrinolytic compound. It has been obtained more recently by
      genetic engineering. Staphylokinase activates plasminogen into plasmin. It is a
      promising new thrombolytic agent for the treatment of acute myocardial infarction
      and thromboembolic disease in general. It is a fibrin specific thrombolytic agent
      which does not decrease plasma fibrinogen level in treated patients. However it
      is antigenic and the group of Louvain has made much effort to reduce its
      antigenicity without decreasing its thrombolytic activity. Mutants with a reduced
      antigenic activity have been recently obtained. These new thrombolytic agents
      could be superior to currently used drugs. Staphylokinase mutants could have a
      better benefit/cost ratio than other thrombolytic agents.

PMID- 9608921
TI  - [The role of season in the incidence of deep venous thrombosis].
AB  - INTRODUCTION: The question of the role of season as a predisposing factor for
      development of venous thromboembolic disease still remains a matter of debate.
      Actually, most reports described a higher incidence of thrombotic disorders in
      winter, while a recent study showed no seasonal variation in the incidence of
      deep vein thrombosis (DVT). These data led us to study the seasonal distribution
      of all outpatients with DVT admitted to our Department over a period of 14 years.
      METHODS: Retrospective review of the files of all outpatients with confirmed
      (venography or ultrasound) DVT of the legs admitted from Jan. 1st 1982 to Dec.
      31st 1995 (n = 512; mean age 59.4 years; 49.4% women). RESULTS: DVT occurred in
      spring in 135 (26.4%), in summer in 104 (20.3%), in autumn in 142 (27.7%) and in
      winter in 131 (25.6%) patients. This distribution appears to be similar to an
      expected uniform distribution [chi 2(3) df = 6.48; p = 0.090 (NS)]. CONCLUSIONS:
      In our study, by investigating retrospectively 512 outpatients with confirmed
      DVT, no correlation was found between season and development of thrombosis,
      suggesting that cold seasons do not represent a predisposing factor for DVT.
      Further large prospective studies are needed in order to validate our data and to
      investigate the clinical implications and the precise role of the season in the
      risk of occurrence of venous thrombosis.

PMID- 9608922
TI  - [Role of the process of endothelium formation on the wall of the aortic
      prosthesis in protection against infection. Experimental study in dogs].
AB  - An experimental canine model was developed in order to evaluate the role of
      endothelialization of aortic prostheses for protection against septicemic
      infection and the utilization of 131I radiolabeled bacteria for vascular
      experimentation. Two groups of dogs were submitted to insertion of a dacron
      prosthesis segment in the abdominal aorta with subsequent infusion of inert 131I
      radiolabeled bacteria. In the first group ("A"), formed by five dogs, the
      infusion was made 30 minutes after the insertion of the prosthesis and in the
      second group ("B"), formed by four dogs, in a new surgery performed 12 weeks
      after. Fragments of the animals' prostheses and aortas were collected after 30
      minutes of septicemia and analyzed by scan electron microscopy and submitted to
      reading of radioactivity uptake by a well-type counter. The microscopy recognized
      a complete endothelialization of the prostheses of dogs of group "B" 12 weeks
      after their insertion. Statistical analysis comparing fragments of non
      endothelialized prostheses, of endothelialized prostheses and aortas demonstrated
      that the lower radioactivity uptake of the endothelialized prostheses in relation
      to non-endothelialized ones was significant (p = 0.0143) and that there was no
      significant statistical difference in uptake in the aortas and in endothelialized
      prosthesis (p = 0.3173). It was, therefore, concluded that prosthesis
      endothelialization fully protected them against septicemic infection; bacteremia
      contaminated all the non-endothelialized prostheses; there was no bacterial
      adhesion in the endothelialized prostheses and the use of bacteria labeled with
      radioisotope 131I is appropriate for the study of infections in vascular
      prosthetic devices.

PMID- 9608923
TI  - [Evaluation of clinical efficacy of a venotonic drug: lessons of a therapeutic
      trial with hemisynthesis diosmin in "heavy legs syndrome"].
AB  - Venous-type symptoms, i.e. painful sensation of heavy, swollen or restless legs,
      influenced by orthostatism and warm environment, significantly alters quality of
      life of a large proportion of women. Although the condition is frequently
      associated with chronic venous insufficiency, no demonstrable hemodynamic
      abnormality of the superficial as well as deep venous systems of the lower limbs
      can be found in many patients. The pathogenesis of this syndrome remains unknown,
      and there is no objective measurement of any biological nor hemodynamic
      parameters that can be used for its assessment. Diosmine and other flavane
      derivatives have been shown beneficial in this condition using various discomfort
      indexes. The aim of this work was to compare the therapeutic efficacy of two
      formulations of the same compound diosmine. In the analysis, particular attention
      was paid to the signification and usefulness of discomfort scales. This study was
      a double-blind, placebo-controlled therapeutic trial, comparing the efficacy of a
      new formulation, hemisynthesis diosmine 600 mg, one tablet per day taken in the
      morning, versus the usual tablet formulation of 300 mg taken twice a day (morning
      and evening). Treatment blindness was assured by the double placebo method. Two
      parallel groups were treated 28 days with one or the other treatment.
      Randomization was performed with stratification by center. The main evaluation
      criteria were a composite scale of venous type symptoms (i.e. the sum of
      individual score 0-4 of each symptom), and a visual analog auto-evaluation scale
      quoted each week by the patient. The global opinion of the physician on treatment
      adequacy to the clinical situation, and the degree of patient satisfaction (four
      grade scales) were used as subsidiary criteria. In order to increase the
      homogeneity of the study sample, inclusion was restricted to non-menopaused women
      aged 18 years and over, having given written informed consent, complaining of
      distressing sensation of heavy legs, without history of venous thrombosis,
      varicose veins, superficial or deep venous reflux at the duplex-scan examination.
      Patients with other causes of pain in the lower limbs, taking analgesic
      medications or requiring elastic stocking were not included. 255 patients
      participated in the trial. Eighteen withdrew, equally distributed in both groups
      (6 lost, 5 interfering diseases, and two dropouts for side effects, namely
      headache and gastric pain). Twenty additional patients complained of detrimental
      events not requiring treatment withdrawal, equally distributed between both
      groups, and mainly involving digestive functions. The results confirmed a similar
      efficacy of the two drug regimens, and a small but significantly better
      improvement of the patients' auto-evaluation of their discomfort on the analogic
      scale (p = 0.021) for hemisynthesis diosmine 600 mg, mainly during the first two
      weeks; for all four criteria, the gamma risk showed that the once-a-day 600 mg
      preparation at least as effective as 300 mg twice daily (p < 0.001). On a
      methodological point of view, the comparison of evaluation criteria showed that
      the composite scale, although giving the feeling of a comprehensive and
      quantitative appraisal of the discomfort in the legs, was almost equivalent to a
      standard four grade rating of heaviness, which appeared as the central symptom of
      this condition. Auto-evaluation through an analogic scale proved to be more
      informative, more sensitive, less influenced by the physician's feelings and
      allow easier assessment of the time-course of the drug's effects. Global
      evaluations by the patient and the physician did not give additional information
      but could be used as quality criteria, assessing the coherence of the results
      obtained with the scales. This study demonstrated a similar efficacy of the two
      drug regimens, with a more rapid effectiveness of the 600 mg preparation taken
      once a day. Auto-evaluation on the analog scale proved to be the most informative
      and effe

PMID- 9608924
TI  - Threshold of shear stress in human blood for healthy and sick subjects.
AB  - It is now well recognized that blood is a yield stress fluid, that is to say that
      it will not flow below a critical threshold level of stress. This is reflected in
      vivo with a cessation of flow threshold, of great importance in circulatory
      physiology and pathophysiology. Values for yield stress obtained by different
      techniques are scarce. Rheometry at low shear rates is one method of obtaining
      values. After mitigating the slip effects on the walls of the rheometer, it has
      been possible to get an approximate value of the yield stress in human blood
      samples in controls and in ill subjects with different hematocrits. A Low Shear
      40 rheometer with a controlled rotation speed was used. Home made geometries were
      used and the shear rate was varied in the range 10(-3) s-1-100 s-1. Fresh blood
      samples from healthy donors and patients were anticoagulated with EDTA.
      Suspensions of red cells in plasma were prepared by removing plasma. The
      measurements were made at 25 degrees C within four hours following blood
      sampling. Particular attention was paid to data acquisition at low shear rates
      (10(-3) s-1, 3.10(-3) s-1, 10(-2) s-1, 3.10(-2) s-1) with a computer linked to
      the rheometer. Shear stress approached a constant value at low shear rates for
      geometries with rough surfaces. Shear stress measured at 10(-3) s-1 was taken as
      an approximation of yield stress. Values were 5 to 6 mPa for hematocrit 60% and
      20 to 25 mPa for hematocrit in the 80 to 90% range. For pathological blood
      samples, accurate measurements were made at shear rate as low as 0.01 s-1.
      Migrational effects were present at 10(-1) s-1 et 3.10(-3) s-1 but they could be
      greatly mitigated by the use of the 170 microns surface roughness.

PMID- 9608925
TI  - [Modulators of leukocytic functions].
AB  - Polymorphonuclear neutrophils (PMN) and monocytes play a role in vascular
      diseases. Animal experimental models, using deleukocytation or injection of anti
      CD11b-anti-CD18 monoclonal antibodies (inhibition of leukocytic adhesion and of
      interaction with the endothelial cell) have confirmed this role in the ischemia
      reperfusion syndrome and in myocardial infarction. In man, increased production
      of oxygen radicals, PMN release of elastase, increased monocyte formation of
      tissue factor (TF) and integrins have been noted in coronary artery disease, in
      chronic arteriopathy of the lower limbs and in association with vascular risk
      factors such as diabetes. Pharmacological alteration of leukocyte hyperactivity
      therefore seems to be justified. Pentoxifylline, used with good effect in
      arteriopathy of the lower limbs, affects numerous leukocytic functions:
      diminution in adherence and in PMN production of free radicals, diminution in the
      formation of TF and cytokines (TNF). Gingkolides reduce leukocytic interactions
      and platelet activation through an anti-PAF (Platelet Activation Factor) action.
      Aspirin may interfere with free radicals and inhibit TF formation. alpha
      tocopherol blocks the activation, by free radicals, of the transcription factor
      NF k B. By altering the TNF and IL-1 cytokines, leukocytic activation can be
      controlled. Other cytokines (IL-4, IL-10) have an immunosuppressive action and
      reduce the formation of TF. The pharmacological targets are therefore multiple.
      Their use in vascular diseases is only at a very preliminary stage.

PMID- 9608926
TI  - [Medical recommendations and references 1997. Stenosis of the origin of the
      cervical internal carotid and the carotid bifurcation: surgery, angioplasty.
      ANAES. National Agency for Accreditation and Evaluation in Health].

PMID- 9608927
TI  - [Nicotine addiction: greatly missing in Congress. Why such indifference...].

PMID- 9608928
TI  - The Department of Veterans Affairs integration of imaging into the healthcare
      enterprise using the VistA Hospital Information System and Digital Imaging and
      Communications in Medicine.
AB  - The United States Department of Veterans Affairs is integrating imaging into the
      healthcare enterprise by using the Digital Imaging and Communication in Medicine
      (DICOM) standard protocols. Image management is directly integrated into the
      VistA Hospital Information System (HIS) software and clinical database. Radiology
      images are acquired with DICOM and are stored directly in the HIS database.
      Images can be displayed on low-cost clinician's workstations throughout the
      medical center. High-resolution diagnostic quality multimonitor VistA
      workstations with specialized viewing software can be used for reading radiology
      images. Two approaches are used to acquire and handle images within the radiology
      department. Some sites have a commercial Picture Archiving and Communications
      System (PACS) interfaced to the VistA HIS, whereas other sites use the direct
      image acquisition and integrated diagnostic display capabilities of VistA itself.
      A small set of DISCOM services has been implemented by VistA to allow patient and
      study text data to be transmitted to image producing modalities and the
      commercial PACS, and to enable images and study data to be transferred back.
      DICOM has been the cornerstone in the ability to integrate imaging functionality
      into the healthcare enterprise. Because of its openness, it allows the
      integration of system components from commercial and noncommercial sources to
      work together to provide functional cost-effective solutions.

PMID- 9608929
TI  - Voice-activated retrieval of mammography reference images.
AB  - We undertook this project to integrate context sensitive computer-based
      educational and decision making aids into the film interpretation and reporting
      process, and to determine the clinical utility of this method as a guide for
      further system development. An image database of 347 digital mammography images
      was assembled and image features were coded. An interface was developed to a
      computerized speech recognition radiology reporting system which was modified to
      translate reported findings into database search terms. These observations were
      used to formulate database search strategies which not only retrieved similar
      cases from the image database, but also other cases that were related to the
      index case in different ways. The search results were organized into image sets
      intended to address common questions that arise during image interpretation. An
      evaluation of the clinical utility of this method was performed as a guide for
      further system development. We found that voice dictation of prototypical
      mammographic cases resulted in automatic retrieval of reference images. The
      retrieved images were organized into sets matching findings, diagnostic
      hypotheses, diagnosis, spectrum of findings or diagnoses, closest match to
      dictated case, or user specified parameters. Two mammographers graded the
      clinical utility of each form of system output. We concluded that case specific
      and problem specific image sets may be automatically generated from spoken case
      dictation. A potentially large number of retrieved images may be divided into
      subsets which anticipate common clinical problems. This automatic method of
      context sensitive image retrieval may provide a "continuous" form of education
      integrated into routine case interpretation.

PMID- 9608930
TI  - An algorithm for automatic segmentation and classification of magnetic resonance
      brain images.
AB  - In this article, we describe the development and validation of an automatic
      algorithm to segment brain from extracranial tissues, and to classify
      intracranial tissues as cerebrospinal fluid (CSF), gray matter (GM), white matter
      (WM) or pathology. T1 weighted spin echo, dual echo fast spin echo (T2 weighted
      and proton density (PD) weighted images) and fast Fluid Attenuated Inversion
      Recovery (FLAIR) magnetic resonance (MR) images were acquired in 100 normal
      patients and 9 multiple sclerosis (MS) patients. One of the normal studies had
      synthesized MS-like lesions superimposed. This allowed precise measurement of the
      accuracy of the classification. The 9 MS patients were imaged twice in one week.
      The algorithm was applied to these data sets to measure reproducibility. The
      accuracy was measured based on the synthetic lesion images, where the true voxel
      class was known. Ninety-six percent of normal intradural tissue voxels (GM, WM,
      and CSF) were labeled correctly, and 94% of pathological tissues were labeled
      correctly. A low coefficient of variation (COV) was found (mean, 4.1%) for
      measurement of brain tissues and pathology when comparing MRI scans on the 9
      patients. A totally automatic segmentation algorithm has been described which
      accurately and reproducibly segments and classifies intradural tissues based on
      both synthetic and actual images.

PMID- 9608931
TI  - Detection of suspected malignant patterns in three-dimensional magnetic resonance
      breast images.
AB  - In this article, a Boolean Neural Network (BNN) is used for the detection of
      suspected malignant regions in 3D breast magnetic resonance (MR) images. The BNN
      is characterized by fast learning and classification, guaranteed convergence, and
      simple, integer weight calculations. The BNN learning algorithm is incremental,
      which allows the addition and deletion of training patterns without unlearning
      those already learned. The incremental learning algorithm automatically reduces
      the training set and trains the network only with those examples estimated to be
      useful. The architecture is suitable for parallel hardware implementation using
      available Very Large Scale Integration (VLSI) technology. The BNN was trained by
      using a set of malignant, benign, and false-positive patterns, extracted by
      experts, from selected MR studies, by using an incremental learning algorithm.
      After training, the network was tested by means of a consistency checking test,
      cross validation techniques, and patterns from actual MR breast images. During
      the consistency test, the BNN was tested by using the same patterns used for
      training. The BNN classification accuracy in this case was 99.75%, proving the
      ability of the BNN to select useful patterns from the training set. Then, a leave
      one out cross-validation (LOOCV) test was done by using patterns from the
      training set and the classification accuracy was 90%. Next, an extended training
      set was created by shifting the original patterns in different directions. A
      cross-validation test was then performed by dividing the set of patterns into a
      training and a test set. Classification accuracy was compared to the nearest
      neighbor classifier. Results showed that the BNN achieved an average of 77%
      classification accuracy while requiring only 34% of the original training set. On
      the other hand, the nearest neighbor classifier achieved an accuracy of 57.9%
      while retaining the whole training set. Another test using actual MR slices
      different from the training set was done and results compared favorably to a
      radiologist's findings. Test results show the BNN's capability to detect
      suspected malignant regions in 3D MR images of the breast. The proposed BNN
      architecture can save the radiologist a great deal of time browsing MR slices
      searching for suspected malignancies.

PMID- 9608932
TI  - Recommendations for image prefetch or film digitization strategy based on an
      analysis of an historic radiology image database.
AB  - Picture archiving and communications systems (PACS) utilize short- and long-term
      storage to provide both rapid retrieval and large storage capacity. Owing to the
      practical limitations imposed on the size of the much faster short-term storage,
      it is important to use an effective algorithm in the retrieval of comparison
      images from long to short-term storage. A strategy must be used to maximize the
      likelihood that the relevant historic images have been previously retrieved into
      short-term memory. Data were collected with a database consisting of 754
      consecutive examinations and 7,723 associated historic studies. The most frequent
      number of previous examinations was zero (11% of patients). In 45% of cases, no
      previous matching examinations had been performed. Two basic strategies of image
      retrieval were evaluated. The first algorithm retrieved the last n studies in
      chronological order. The second strategy tested was retrieval based on a defined
      interval of time. This strategy was found to be less efficient. By using the
      former strategy, a 91% success rate (defined as successful retrieval of the
      previous matching exam) was achieved with retrieval of only 30% of the prior
      exams. The second approach required retrieval of 70% of the prior exams to
      achieve a 90% success rate for the previous matching exam. However, the data from
      this latter strategy suggest that examinations are often ordered in clusters.
      Thus, there was found to be a 72% likelihood that a previous matching exam, if
      present, would available on a PACS after only 1 week of operation, and an 80%
      chance after only 1 month of operation. The data therefore suggest that
      digitization of film in a new PACS environment might not be necessary owing to
      the relatively short period of time required to populate the database with
      historical studies.

PMID- 9608933
TI  - The Society for Computer Applications in Radiology.

PMID- 9608934
TI  - [Genes of DNA stabilization and carcinogenesis].

PMID- 9608935
TI  - [Tumor suppressor genes].

PMID- 9608936
TI  - [Gene therapy today and tomorrow].

PMID- 9608937
TI  - [Logical regulation of DNA polymerase mutagenesis and autonomous 3'-5'
      exonuclease].

PMID- 9608938
TI  - [Position of a template in the decoding region from affinity modification of
      human ribosomes by a photoactivated derivative of the oligoribonucleotide
      pGUGUUU].

PMID- 9608939
TI  - [System of regulating expression of antirestriction genes ardA and ardB, coding
      for the transmissive IncN plasmid pKM101 (R46)].

PMID- 9608940
TI  - [Features of the structure, expression and chromosomal mapping of the nucleotide
      sequences of Hmob3 and Hmob33, obtained from a human medulla oblongata cDNA
      library].

PMID- 9608941
TI  - [Functional sites of pro- and eukaryotic genomes: computer modeling and
      predicting activity].

PMID- 9608942
TI  - [Molecular mechanisms of nucleic acid biosynthesis validity. Comparison of
      results of computer modeling with experimental data].

PMID- 9608943
TI  - [Molecular-genetic disruption in area near the BRCA1 gene, associated with
      ovarian carcinoma].

PMID- 9608945
TI  - [Connection of multiple sclerosis in the Russian population with alleles of the
      major histocompatibility complex DRB1 gene].

PMID- 9608944
TI  - [Exon-intron organization rpb10+ and rpc10+ genes of Schizosaccharomyces pombe,
      coding for mini-subunits of nuclear RNA-polymerase I-III].

PMID- 9608946
TI  - [Antirestriction activity of the transmissive plasmid R64 (IncI1) is determined
      by the arsR gene].

PMID- 9608947
TI  - [Structural aspects of protein thermostability].

PMID- 9608948
TI  - [Probing the structure of triplex and parallel DNA using chemical ligation].

PMID- 9608949
TI  - [Intracellular solubility of hybrid growth hormones].

PMID- 9608950
TI  - [Antisense RNA, suppressing the reproduction of bovine leukemia virus in cell
      culture, binds effectively with an RNA target in vitro].

PMID- 9608951
TI  - [A proposed new mammalian cell protein kinase, associated with microtubules].

PMID- 9608952
TI  - [Analysis of the cell cycle structure and apoptosis of E1Aad5-immortalized rat
      cells after exposure to DNA damaging agents].

PMID- 9608953
TI  - [Differentiation of neurons and synapses of mossy fibers in transplants of fascia
      dentata developing in the rat neocortex].
AB  - Embryonic fascia dentata tissue isolated from the hippocampus was transplanted
      heterotopically into the neocortex of adult rats. Ultrastructural characteristics
      of neurons and synapses in transplants were studied nine months later. It has
      been found that the main types of neurons present in fascia dentata undergo
      differentiation in the transplants, and a dense neuropile containing various
      types of synapses is produced. A characteristic feature of the transplanted
      neurons is the presence of additional microspines on somatic and dendrite
      surfaces; this appears to be due to a deficiency of external and internal
      afferents. Gigantic synaptic terminals of granule cell axons (mossy fibers) in
      transplants possess unique morphological characteristics, which allow their
      identification in a complex neuropile. Just as in situ, they form two types of
      contacts: chemical asymmetric contacts with dendrite spines and desmosome-like
      ones with dendrite surface characteristics. However, accumulations of large
      vesicles with electron-dense centers can often be observed near the active zones
      of the synapses, and desmosome-like connections are more prominent. The most
      important feature is that gigantic synapses in transplants use midsize and small
      dendrites as postsynaptic targets up to terminal branches, and they contact with
      spines of the usual shape and size, whereas in situ terminal synaptic contacts of
      mossy fibers are formed only with gigantic processes of initial segments of the
      large apical dendrites. Thus, in the absence of normal synaptic targets, mossy
      fibers can produce contacts having all features of functional synapses, but with
      atypical postsynaptic structures.

PMID- 9608954
TI  - [Effect of cryopreservation on the morphology of preimplantation embryos of the
      ISIAH rat line].
AB  - Micronuclei of preimplantation embryos of the hypertensive rat strain with
      inherited spontaneously induced arterial hypertension (ISIAH) are studied. Also
      studied are the formation of micronuclei and other morphological changes in these
      embryos after freezing, cryoconservation, and consequent transplantation to
      Wistar recipient rats. Analysis of semithin sections demonstrates that the above
      procedures lead to the formation of micronuclei in most embryos, while the shape
      of nuclei changes in only some embryos. There is a tendency towards perinuclear
      location of organelles and inclusions and to the partial disappearance of
      polarity in the majority of blastomeres. We believe that the increase in the
      number of micronuclei can be associated with a certain selection of embryos
      during cryoconservation and transplantation.

PMID- 9608955
TI  - [The interaction of homotypic and heterotypic embryonic stem cells with
      developing embryos].
AB  - It has been demonstrated that embryonic stem cells form adhesive contacts with
      external blastomeres of mouse morula, while there is no such contact with
      blastocysts. The development of morula in the blastocysts is delayed inside a
      dense layer of such cells; however, in some cases, external blastomeres of the
      morula begin to differentiate into trophoblastic cells. The introduction of an
      excessive number of embryonic stem cells (15-20) into a 4-8-cell embryo results
      in abnormal development. When heterotypic embryonic mink stem cells are co
      cultivated, they show only very weak adhesion with mouse blastomeres and are
      displaced as a result of compactization. When blastocysts are formed after the
      injection of heterotypic embryonic stem cells, such cells remain in the
      perivitelline space. In some cases, heterotypic embryonic stem cells continue to
      be determined in the trophoblastic direction and produce trophoblastic vesicles
      autonomously. The role of cell interaction in the determination of cells during
      early mammalian development is discussed.

PMID- 9608956
TI  - [Embryo- and genotoxic effects of two endosulfan forms in the culture of rat and
      mouse pre- and postimplantation embryos].
AB  - We studied embryo- and genotoxic effects of two forms (powder and microcapsular)
      of organochlorine insecticide and acaricide endosulfan in rat and mouse cultures
      of pre- and postimplantation embryos. The substance caused embryonic death,
      teratogenesis, and inhibited embryonic growth. Embryo cultivation in the serum
      obtained from the rats 1-48 h after single peritoneal introduction of highest
      bearable endosulfan dose allowed us to compare time pattern of the embryotoxic
      factors in the animal blood for the both substance forms. Microcapsular
      endosulfan induced much later appearance of the embryotoxic factors in the rat
      blood, had lower embryolethal and teratogenic effects, but prolonged the presence
      of pathogenic factors in the animal as compared to the powder form. We propose
      that embryo- and genotoxic activity of endosulfan increases in the course of its
      biotransformation.

PMID- 9608957
TI  - [Cytogenetic analysis of sister chromosome sets in the second polar body and in
      pronuclei of unicellular mouse embryos. I. Frequency and origin of aneuploidy in
      embryos heterozygous for the reciprocal chromosome translocation T[14;15]6Ca].
AB  - We carried out a cytogenetic study of ovulating oocytes and unicellular embryos,
      heterozygous by reciprocal chromosomal translocation T[14;15]6Ca. Okadaic acid
      was used to induce premature condensation of the interphase chromosomes in the
      embryos, and the number of G1 chromosomes was counted in the second polar body
      and pronuclei. It was shown that cytogenetic analysis of the sister chromosomal
      sets adequately determines the frequency of chromosomal segregation errors during
      oocyte meioses I and II. Trisomy and monosomy were observed in 36.2% embryos,
      while 2.2% featured tetrasomy or double monosomy. Errors of the first meiotic
      division caused aneuploidy in 28.5% embryos; trisomy and monosomy resulted from
      the homologs non-disjunction and chromatid presegregation in 17.6 and 10.9%,
      respectively. Numeral chromosomal aberrations in 4.1% of the embryos resulted
      from abnormal chromosomal segregation during oocyte meiosis II, while paternal
      chromosomal aberrations were found in 5.8% embryos. The main advantage of the
      proposed method is not only the higher accuracy in estimating the meiotic error
      frequency, but also the possibility to trace the origin of aneuploidy in
      mammalian embryos.

PMID- 9608958
TI  - [Cytologic mechanisms of postnatal growth of adrenal chromaffin tissue].
AB  - We have studied the contribution of proliferation and hypertrophy of glandular
      cells to the ontogenetic growth of adrenal chromaffin tissue using several
      methods (organometry, cytometry, cytophotometric quantitation of DNA in the
      nuclei, radioautographic analysis of 3H-thymidine incorporation, calculation of
      the mitotic index and proportion of binuclear cells, as well as stereological
      analysis). Mitotic division of diploid glandular cells is the main cellular
      mechanism of postnatal growth of chromaffinocytes. It is most prominent during
      the first 2 weeks of life and is maintained at a rather high level throughout the
      life of animals (the daily proliferative pool in 6-month-old and 30-month-old
      rats equals 0.3%). Development of cellular hypertrophy has been noted during the
      first 6 months after birth. The population of chromaffinocytes throughout life is
      practically diploid; the proportion of tetraploid (binuclear) cells does not
      exceed 1-1.5%. The growth of adrenal chromaffin tissue during the first month of
      life is generally supported by hyperplasia and hypertrophy of norepinephrocytes
      and later of epinephrocytes. The contribution of cell proliferation and
      hypertrophy to postnatal growth of each subpopulation appears to be equal.

PMID- 9608959
TI  - [Effect of local application of aminazine on transcallosal responses in cats
      during postnatal ontogenesis].
AB  - We studied the effect of aminazine on transcallosal response in kittens during
      different periods of postnatal ontogenesis. We demonstrate that at the beginning,
      aminazine does not influence transcallosal response, but from Days 7-12 after
      birth, it leads to full inhibition of the negative component. In older kittens,
      aminazine also reverses late components of the response and decreases their
      amplitude.

PMID- 9608960
TI  - Preemptive analgesia for postop pain.

PMID- 9608961
TI  - Total intravenous anaesthesia (TIVA) in paediatrics: advantages and
      disadvantages.

PMID- 9608962
TI  - Prevention of halothane-induced bradycardia: is intranasal premedication
      indicated?
AB  - Eighty ambulatory surgical patients with ASA physical status 1 and 2, aged 1-10
      years, were studied. One group received intranasal (IN) midazolam 0.25 mg.kg-1; a
      second group received IN 0.25 mg.kg-1 of midazolam plus 0.02 mg.kg-1 of atropine;
      the third group received 0.25 mg.kg-1 of midazolam plus 0.02 mg.kg-1 of atropine
      administered intramuscularly, and the fourth group received IN saline drops. All
      patients were anaesthetized with nitrous oxide, oxygen and halothane administered
      via mask. Heart rate (HR) was recorded every minute up to start of surgery.
      Children receiving midazolam had better preoperative sedation and anaesthesia
      induction scores. The IN administration of neither midazolam alone nor midazolam
      atropine altered the incidence or degree of halothane-induced bradycardia.

PMID- 9608963
TI  - A modified technique of tubeless anaesthesia for microlaryngoscopy and
      bronchoscopy in young children with stridor.
AB  - Sixty children including neonates and infants, with stridor undergoing
      investigations under general anaesthesia, were studied retrospectively. General
      anaesthesia was induced using an inhalational technique with halothane and was
      maintained with propofol infusion without the use of tracheal intubation. The
      ages ranged from three days to two years and five months. In most of the cases
      after propofol infusion, there was a slight drop in blood pressure without change
      in heart rate. This modified technique was found to be satisfactory in most of
      the cases.

PMID- 9608964
TI  - Double volume exchange transfusion for ABO incompatible liver transplantation in
      paediatric patients: intraoperative and preoperative approach.
AB  - Double volume blood exchange transfusions (DBVET) were used to reduce the serum
      antibody levels in six paediatric patients receiving ABO incompatible hepatic
      allografts. In four patients, the exchange transfusions took place on the ward
      prior to surgery. In three of these four patients who had titres measured, the
      anti-A IgM titres fell from 1024 to 64, 64 to 8, and 128 to 16, respectively. The
      anti-A IgG titres fell from 32 to 16 and 512 to 64 in two patients, but rose from
      16 to 32 in the third. In two patients DBVET were performed intraoperatively
      using a rapid infusion device. The IgM titres fell from 256 to 32 and 64 to 1,
      respectively, and the IgG titres fell from 16 to 4 and 2 to 0. Intraoperative
      DBVET can acutely and effectively reduce blood group antibodies. Intraoperative
      DBVET may reduce graft ischaemia time and allow red blood cell salvage.

PMID- 9608965
TI  - Progressive hyperthermia during thoracoscopic procedures in infants and children.
AB  - We describe the development of progressive hyperthermia during thoracoscopic
      procedures in infants and children. Twelve patients (four infants and eight
      children) underwent closure of a patent ductus arteriosus using the video
      assisted technique. A progressive increase in body temperature of more than 2
      degrees C occurred in six of the patients during surgery. The increase in body
      temperature correlated inversely with body weight and directly with duration of
      surgery (r = -0.76, P = 0.003 and r = 0.68, P = 0.01, respectively). We found
      that the thoracoscope produces 28.5 joule.min-1 of constant energy in vitro. Our
      findings show progressive hyperthermia during thoracoscopic procedures, due to
      energy release from the thoracoscope. This could be a significant complication in
      infants undergoing prolonged operations.

PMID- 9608966
TI  - A comparison of intubation success for paediatric transport team paramedics using
      lighted vs regular tracheal tube stylets.
AB  - We conducted a prospective randomized study of success rate and time to
      intubation using Trachlight and Surch-Lite lighted stylets versus a regular
      tracheal tube stylet, in a training setting. Participants, 18 paediatric
      transport paramedics, performed two intubations with each of the three devices,
      using an airway management trainer. There was no significant difference in mean
      time for intubation between the three devices. The times for external
      confirmation of correct tube placement were comparable using the two lighted
      stylets. External confirmation of the tube placement using the lighted stylets
      was quicker than laryngoscopic visualization. In darkness, with a nonfunctioning
      laryngoscope, intubations were successfully performed 100% of the time with the
      lighted stylet, but only 11% of the time with the regular stylet. All paramedics
      felt that a lighted stylet would be a useful airway management adjunct for the
      transport environment for complicated intubations or for use in very high or low
      levels of ambient light.

PMID- 9608967
TI  - Stridor in the neonate and infant. Implications for the paediatric anaesthetist.
      Prospective description of 155 patients with congenital and acquired stridor in
      early infancy.
AB  - One hundred-and-fifty-five neonates and infants up to the sixth month of
      postnatal age were investigated to reveal the cause of clinically relevant
      stridor. In 100 patients congenital stridor was found, in 55 children the stridor
      was considered to be acquired. A curled, soft epiglottis, almost synonymously
      used with the diagnosis of congenital stridor, was found in 7% only, indicating
      different methods of investigation and different selection of patients compared
      to previous years. In acquired stridor the majority of infants showed laryngeal
      and tracheal trauma, mostly due to the use of too large tracheal tubes.

PMID- 9608968
TI  - Comparison of morphine requirements for sedation in Down's syndrome and non
      Down's patients following paediatric cardiac surgery.
AB  - Anaesthetists recognize that children with Down's syndrome require special
      management in a number of clinical situations. There is a widespread clinical
      impression that it is difficult to achieve adequate sedation and that, following
      cardiac surgery, these children require higher doses of morphine and additional
      sedative agents compared to patients without Down's syndrome. We conducted a
      retrospective chart review of 16 Down's syndrome and 16 matched non-Down's
      syndrome children who underwent cardiac surgery between 1984 and 1991. The
      average dose of morphine (continuous infusion) administered per hour was higher
      in the Down's syndrome group than in the non-Down's syndrome group. The
      difference was not statistically or clinically significant until the third
      postoperative day. Down's syndrome patients were more likely to still be
      receiving morphine on Day 3 than non-Down's patients (P < 0.05). The Down's
      syndrome patients were also more likely to receive additional sedatives and
      skeletal muscle relaxants.

PMID- 9608969
TI  - Examination of acetaminophen for outpatient management of postoperative pain in
      children.
AB  - We have examined acetaminophen (paracetamol) dosing for outpatient management of
      posttonsillectomy pain in children. Forty children, 5-15 years of age, undergoing
      tonsillectomy and their parents were randomly assigned to use a scheduled
      administration of acetaminophen in weight appropriate doses, 60 mg.kg-1.24h-1
      orally, 90 mg.kg-1.24h-1 rectally, or to use acetaminophen 'as needed' according
      to present standards (control group). Postoperative pain was assessed by the
      child using the poker chip tool for the first three days after discharge. The
      prevalence of pain amongst all the children was high. The second day after
      discharge 22%-64% of the children in the study group and 36%-73% of the children
      in the control group rated severe pain. Recommended dose ranges of acetaminophen
      do not provide sufficient pain relief in children following tonsillectomy.
      Further studies are required to determine, whether higher doses of acetaminophen
      or analgesics with different analgesic properties will lead to improved analgesia
      in children following tonsillectomy.

PMID- 9608970
TI  - Comparison of granisetron and droperidol in the prevention of vomiting after
      strabismus surgery or tonsillectomy in children.
AB  - This prospective, randomized, double-blinded study evaluated the antiemetic
      efficacy of granisetron and droperidol in 80 ASA physical status I children, aged
      4-10 years, undergoing strabismus surgery or tonsillectomy with or without
      adenoidectomy. After anaesthetic induction, the patients received either
      granisetron (40 micrograms.kg-1, n = 40) or droperidol (50 micrograms.kg-1, n =
      40) intravenously. The incidence of vomiting during the first 24h after
      anaesthesia was 15% and 38% after administering granisetron and droperidol,
      respectively (P = 0.02). The requirement for rescue antiemetic therapy for the
      treatment of two or more episodes of vomiting was 0% with granisetron and 18%
      with droperidol (P = 0.001). In conclusion, granisetron was superior to
      droperidol in reducing the incidence and frequency of postoperative vomiting in
      paediatric patients.

PMID- 9608971
TI  - Diagnosis and anaesthesia management of haemophilia during the neonatal period.
AB  - We report here the case of a newborn infant admitted to our hospital for moderate
      gastro-intestinal bleeding. Despite abnormal value for aPTT, diagnosis of
      moderate haemophilia A was only made preoperatively when surgery was deemed
      necessary to treat pyloric stenosis. Clinical circumstances of the diagnosis and
      anaesthesia management of haemophilia during the neonatal period are discussed.

PMID- 9608972
TI  - Anaesthesia and mitochondrial disease.
AB  - Mitochondrial diseases, or encephalomyopathies, are an uncommon, heterogeneous
      group of disorders with variable clinical course and presentation. Many of these
      patients present for surgery, or undergo anaesthesia in the course of
      investigation of their illness. Unfortunately, little information exists on their
      management in anaesthetic texts and the literature. We report on the anaesthetic
      management of a paediatric patient with mitochondrial disease, and briefly
      discuss the pathophysiology and anaesthetic implications of these disorders.

PMID- 9608974
TI  - Recurrent intraoperative lobar collapse.
AB  - We present a case report of an asymptomatic 12-year-old girl who was incidentally
      noted to have a collapsed upper lobe of her right lung during anaesthesia for
      angiography. After initial success at reexpansion using manual ventilation and
      suctioning, the lobe collapsed again some 15 min later. Physiological parameters
      remained stable throughout. Consent was obtained for fibreoptic bronchoscopy
      which was performed uneventfully and resulted in reexpansion of the lobe. We
      discuss the difficulty in identifying patients at risk of this complication, the
      need for therapeutic intervention and the issue of consent.

PMID- 9608973
TI  - Anaesthetic management of the surgical separation of a pair of thoracopagus
      cardiopagus twins.
AB  - We describe the anaesthetic management of the surgical separation of a pair of
      thoracopagus-cardiopagus twins with a common right atrium and a myocardial tissue
      bridge containing vascular channels between their ventricles. One of them died
      during the procedure, the surviving twin is now two years old. The survival of
      one twin for two years without significant sequelae, after the surgical
      separation of twins with shared right atrium and fused ventricles, has not
      previously been reported. Careful preoperative assessment is essential to
      anticipate potential serious problems during the procedure.

PMID- 9608975
TI  - Improvement of intraoperative somatosensory evoked potentials by ketamine.
AB  - Many anaesthetics effect the latency and amplitude of somatosensory evoked
      potentials (SSEP). We present a patient who underwent two anterior/posterior
      spine fusions (A/PSF) at age 11 and 12 years old after resection of a spinal
      astrocytoma. She did have residual neurologic deficits of her lower extremities.
      SSEPs were unobtainable during the first surgery using an opioid-based
      anaesthetic. A ketamine-based anaesthetic was used for the second surgery and
      SSEPs were easily monitored. No other factors seem to have changed between the
      two surgeries. The anaesthetic management during each procedure is reviewed and
      the contributions of other factors to SSEP monitoring discussed.

PMID- 9608976
TI  - Anaesthesia and Prader-Willi syndrome.
AB  - A review of a case series of sixteen anaesthetics in eight cases was undertaken
      to determine whether children with Prader-Willi syndrome present particular
      problems to the anaesthetist. Children in an early stage of the condition who are
      below their centile for weight present no specific problems. Children who are
      heavier than 97th centile weight have problems associated with their obesity:
      difficult intravenous access and sleep apnoea. Scoliosis was noted in both groups
      and was not associated with problems after minor surgery.

PMID- 9608977
TI  - An inexpensive arterial line protector.

PMID- 9608978
TI  - Oesophageal intubation in an infant for oesophageal dilatation.

PMID- 9608979
TI  - Variability of concentrations after rectal paracetamol.

PMID- 9608980
TI  - Use of the laryngeal mask airway to preoxygenate in a paediatric patient with
      Treacher-Collins syndrome.

PMID- 9608981
TI  - Use of laryngeal mask airway in two children with upper airways abnormalities.

PMID- 9608982
TI  - [Respiratory impact of new anesthetic agents].
AB  - Respiratory depression is induced by the great majority of anaesthetic agents and
      is responsible for the morbidity and mortality and is the prime complication of
      anaesthesia. However, for several years newer agents are available which are
      characterised by equal or superior power although the duration of their residual
      effects, in particular their respiratory effects are considerably reduced. This
      development leads to the possibility that the newer agents will enable a
      reduction in the respiratory morbidity associated with anaesthesia.

PMID- 9608983
TI  - [The evaluation of the quality of life in asthma patients. Value and
      implementation].
AB  - Asthma, as a chronic condition, alters individual's day-to-day life in
      functional, emotional and social domains. There has been a recent upsurge of
      interest in the assessment of quality of life in asthmatic patients. Indeed,
      there is growing evidence that conventional outcomes of asthma (symptoms
      assessments, functional measures...) although important, may not detect all the
      changes experienced by patients. Quality-of-life instruments target two distinct
      properties. First, discriminative instruments are needed to distinguish between
      individuals or groups of patients. Second, an evaluative instrument is required
      to detect such changes in an individual or group of patients, as occur in
      clinical trials. There are now a number of quality-of-life instruments, with
      strong measurement properties, that can be used in clinical trials.

PMID- 9608984
TI  - [Mineral analysis and study of asbestos pathology].
AB  - Several tools are available for the evaluation of the exposure to asbestos,
      particularly occupational questionnaire and mineralogical analysis of biological
      samples. These analysis allow quantification of the level of retention of
      asbestos fibres in the respiratory tract. Two groups of analysis may be used:
      quantification of asbestos bodies in sputum, bronchoalveolar lavage fluid or lung
      tissue samples using light microscopy; quantification and identification of
      asbestos fibres in bronchoalveolar lavage fluid or lung tissue using analytical
      electron microscopy. Profiles of lung retention of asbestos bodies or asbestos
      fibres have been described in various asbestos-related disorders, and reference
      values are available in control populations mainly for asbestos bodies using
      light microscopy. Mineralogical analysis of biological samples is not required
      for compensation of occupational asbestos-related diseases. However, this type of
      analysis may prove to be useful to the chest physician when looking for the
      etiology of some nonspecific respiratory diseases (interstitial pulmonary
      fibrosis, lung cancer), particularly when the occupational questionnaire is not
      contributive. As they are quite easier and less expensive, analysis using light
      microscopy will be performed first.

PMID- 9608985
TI  - [Thoracic infections in immunocompetent patients. The contribution of computed
      tomography].
AB  - Chest X-Ray is the most accurate method of imaging for infectious diseases in an
      immunocompetent patient. Computed tomography (CT) may be useful in certain
      circumstances, particularly in case of atypical findings at the time of diagnosis
      or in case of complications. CT helps to detect and perform a complete study of
      the lesions, some aspects being very suggestive of a diagnosis, as in post
      primary active tuberculosis. CT may also detect an unknown underlying etiology.
      Multiplanar reformations with helical CT can be useful for example in case of
      empyema. In case of non tuberculous bacterial infections, CT is mainly
      recommended when abscess and empyema are difficult to differentiate or in case of
      pleural complications with possible percutaneous treatment. In case of
      tuberculosis, CT may be indicated when clinical and chest X-Ray findings are
      discordant, in case of mediastinal adenopathies, when reactivation is suspected
      or in case of complications as hemoptysis. A baseline CT examination could be
      proposed at the end of a specific treatment to facilitate the diagnosis of
      reactivation tuberculosis. A nontuberculous mycobacterial infection should
      finally be suspected in front of peculiar CT findings.

PMID- 9608986
TI  - [The sickle cell anemia lung from childhood to adulthood].
AB  - The pulmonary complications remain the prime cause of morbidity and mortality in
      sickle cell disease. The pathogenetic mechanisms consists both of an alteration
      of the rheological properties of the blood, the existence of a hypercoagulability
      state and above all specific interactions between the abnormal sickle cells and
      the vascular endothelium and a dysregulation of the vascular reactivity in which
      nitrous oxide intervenes. The acute chest syndrome (ACS) is characterised by
      chest pain with dyspnoea and recent radiological abnormalities and it is an acute
      lung complication whose problem is one of aetiology. The infectious pneumonias
      are rarely documented. On the other hand, alveolar hypoventilation linked to
      infarcts of the thoracic ribs, thoracoabdominal trauma, subdiaphragmatic pain,
      the administration of analgesics causing respiratory depression, obesity or sleep
      disturbance are frequent causes of ACS. Bronchoalveolar lavage has revealed a
      frequency of fat emboli following infarcts in the long bones. Pulmonary emboli is
      rarely a cause. Pulmonary thrombosis is a serious complication, the diagnosis is
      difficult and is seen in a predisposed clinical setting. The treatment of ACS
      rests on controlled hydration and antibiotic therapy, oxygen therapy and
      controlled analgesic therapy. The indications for blood transfusion and for
      exchange transfusion merits a better evaluation. In the long term patients with
      sickle cell disease present with a failure of normal thoracopulmonary growth with
      a restrictive ventilatory defect and progressive diminution in the transfer
      factor of carbon monoxide with age. A history of ACS favours chronic lung
      disease. Pulmonary arterial hypertension is less frequent.

PMID- 9608987
TI  - [Epidemiologic followup of cases of tuberculosis in the medical-social centers of
      Paris for the year 1994].
AB  - This study was carried out in 280 patients in 1994 in five medico-social centres
      (CMS) in the city of Paris for the follow up of treatment tuberculous disease.
      The group represented approximately one fifth of the tuberculous patients in
      Paris. 90.7% of the subjects were of foreign origin, predominantly African.
      Amongst these 280 patients, 80% were unemployed and 64.6% without social security
      protection. Their tuberculous disease did not differ on clinical grounds from
      those of the general population but they were less often vaccinated with BCG.
      They are also less often co-infected with the HIV virus (4.4 vs 12-16%). The
      level of resistance to isoniazid and rifampicin was 1.4%. A cure was certainly
      achieved in 73.5% of the patients. For the remainder, the absence of information
      and the loss to follow up prevented us from having a definite answer. The
      patients lost to follow numbered 56 and represented 20% of the group.

PMID- 9608988
TI  - [Bronchial endoscopy under local anesthesia and pain in children. The value of a
      nitrous oxide-oxygen combination].
AB  - To evaluate the efficacy of continuous administration of 50% nitrous oxide in
      oxygen for reducing pain during flexible fiberoptic bronchoscopy 32 children aged
      3-60 months were randomly assigned to an experimental or a control group.
      Indications for endoscopy included persistent atelectasis (6), wheezing (10)
      cystic fibrosis (2) pneumonia (11) persistent cough (3). All patients received
      Midazolam (0.3 mg/kg) atropine (20 mcg/kg) intra rectaly 20 minutes before the
      procedure. The flexible fiberoptic bronchoscope (Olympus BF3C4) was inserted
      transnasally through a face mask. Topical anesthesia with 1% lidocaine
      hydrochloride (3 mg/kg) was applied to the nose, larynx, trachea and bronchial
      tree over 15 minutes through the suction chanel of the bronchoscope. All patients
      were monitored with a pulse oximeter and a cardiac monitor. The experimental
      group (n = 16) received 50% nitrous oxide in oxygen prior (3 minutes) and during
      flexible fiberoptic bronchoscopy, the control group (n = 16) received only
      oxygen. We measured pain of the children by a behavioral observation scale
      (Children's Hospital of Eastern Ontario Pain Scale: CHEOPS) at each phase of
      topical anesthesia during bronchoscopy in the two groups. At the end of
      bronchoscopy physician's satisfaction was scored by a visual analogue scale (VAS
      0-100) in which 0 corresponded to absence of satisfaction. Nitrous oxide was
      associated with lesser pain scores than those with oxygen. Physician
      significantly preferred these procedure compared with oxygen. No complication
      occurred during procedure. Combined with local anesthesia midazolam and atropin
      the administration of 50% nitrous oxide in oxygen seems a better choice for
      flexible fiberoptic bronchoscopy in children and should be used routinely.

PMID- 9608989
TI  - [Quantitative bibliographic analysis of French clinical research in the treatment
      of bronchopulmonary cancer].
AB  - A retrospective analysis by searching Medline to assess various criteria
      regarding the quality of publications in recent years in the treatment of
      bronchial cancer in France. Following some pre-defined principles for inclusion,
      103 references corresponding to 90 papers were retained for this study. The data
      analysed had been the method of publication (45 abstracts and 58 articles), the
      origin of the study based on the place and the specialty of the first signatory
      to publication, the subject of the study (42 out of the 90 studies were on
      chemotherapy), the population of the patient studies (56 concerned non small cell
      cancer), the methodology of the study which most often used the rules for open
      phase II trials and only 13 times was it a phase III study, also the number of
      patients included was recorded. A tentative interpretation of the weak and strong
      points of French lung cancer research was carried out based on this analysis and
      has led to the proposition for the creation of a confederation of clinical
      research in this area.

PMID- 9608990
TI  - [Osmolarity of solutions used in nebulization].
AB  - Inhaled medications are widely used in patients suffering from bronchial
      diseases. Beside their pharmacological properties, nebulised solutions have
      physico-chemical characteristics that can alter bronchial reactivity. Non
      isotonic solutions can induce a bronchial hyperresponsiveness and/or a severe
      bronchonconstriction. Nevertheless, multiple drugs are used for nebulisation
      despite their unknown osmolarity. The aim of this study was to measure the
      tonicity of drug solutions commonly used for nebulisation in patients suffering
      from bronchial disease. Drug solutions were prepared either according to
      manufacturer recommendations or by diluting the stock in 5 ml of NaCl (0.9%) or
      H2CO3 (0.14%). Although bronchodilatator solutions (i.e. salbutamol, terbulatine,
      ipratropium bromide) were nearly isotonic, some drugs prepared for nebulisation
      had either a very high (e.g. mesna, netilmicine) or a very low (e.g. gomenol,
      sodium cromoglycate) tonicity. These values may be responsible for
      bronchoconstriction. Some hypertonic solutions, prepared with drugs such as
      acetylcytein or netilmycin, are not commercialised for nebulisation but are
      commonly used for aerosol therapy. In addition, solutions initially isotonic
      could become significantly hypertonic towards the end of nebulisation. Taken
      together, these results suggest that non-isotonic solutions should be used with
      caution specially in patients with bronchial hyperresponsiveness, even when
      aerosol therapy is prescribed for upper airways.

PMID- 9608991
TI  - [Desquamative interstitial pneumopathy: a rare form of diffuse interstitial
      pneumopathy].
AB  - Desquamative interstitial pneumonia (PID) is a rare disorder initially described
      by Liebow in 1965. It is characterised by the presence of an interstitial
      pneumonia consisting of minimal lesions of interstitial fibrosis and by the
      accumulation of a rich intraalveolar cellular material principally composed of
      macrophages. Numerous aetiologies have been found particularly that due to long
      term Nitrofurantoin. We report the observation of a 57 year old patient, a
      cigarette smoker, in whom the diagnosis of PID was made after histological
      examination of a lung biopsy. Based on this observation the pathogenesis and
      possible different aetiologies of PID are discussed.

PMID- 9608992
TI  - [Acute diffuse interstitial pneumopathy following docetaxel (Taxotere). Apropos
      of 2 cases].
AB  - Docetaxel, a new chemotherapeutic agent, has demonstrated activity in non-small
      cell lung cancer and breast cancer. Toxicities associated with treatment using
      docetaxel include hypersensitivity reactions and fluid retention, which can be
      prevented by pretreatment with corticosteroids. We describe herein two cases of
      acute interstitial pneumonitis after administration of docetaxel to patients
      suffering from metastatic non-small cell lung cancer. A pulmonary toxicity of
      docetaxel from an hypersensitivity reaction is likely because of symptoms course,
      radiological demonstration of an interstitial pneumonitis, lack of an infectious
      etiology and of clinical response to antibiotic treatment, and rapid recovery
      with corticosteroids. This unusual pulmonary toxicity has been rarely described
      with docetaxel, as transient pulmonary infiltrates have been observed during
      treatment with paclitaxel. The possibility of an hypersensitivity pneumonitis
      must be taken into account when a patient with docetaxel treatment presents
      pulmonary infiltrates.

PMID- 9608993
TI  - [Uveitis, arthralgia and pseudo-jaundice in a HIV seronegative patient due to
      rifabutin].
AB  - Rifabutin is an effective drug in the treatment of Mycobacterium avium complex
      (MAC). Rare adverse effects have been described in non immunocompromised
      patients. We report the case of a 35 year-old woman, negative for the human
      immunodeficiency virus (HIV), who had an isolated pulmonary infection caused by
      MAC. Under Rifabutin (600 mg/day), Clarithromycin and Ethambutol, an uveitis,
      associated with a pseudojaundice and polyarthralgia, appeared, while pulmonary
      infection improved. Improvement of adverse effects was obtained with non-steroid
      anti-inflammatory drugs, local steroid treatment for uveitis and lower doses of
      Rifabutin (300 mg/day). Those adverse effects have not been previously described
      with this dose of Rifabutin in a non HIV patient. The mechanism remained unknown.
      The decrease of Rifabutin doses associated with symptomatic treatments allow the
      preservation of an effective treatment for MAC infection.

PMID- 9608994
TI  - [Partial left ventriculectomy. Data update, possible indications, and future
      perspectives].

PMID- 9608995
TI  - [Cardiomyopathies. A critical vision of the classification concept].

PMID- 9608996
TI  - [Clinical-epidemiologic indications for echocardiographic assessment in the
      neonatal period. Value of risk groups].
AB  - PURPOSE: An echocardiographic study was performed in newborns from risk groups,
      with the aim of to determining prevalence and to evaluate the indications for
      this test in the neonatal period. METHODS: One hundred fifty six newborns were
      studied. They were admitted to the Newborn ward of the Department of Obstetric of
      the HC-FMUSP, in the period of November 91 to April 93, from mothers with
      congenital heart disease or diabetes, low birth weight newborns, with
      extracardiac malformations, cardiac signs and/or congenital infections. RESULTS:
      The observed prevalence was 21.8%, greater than that of the general population
      (0.8-1.2%). The group composed by 27 children with extracardiac abnormalities
      presented the largest prevalence when compared with the other groups (40.7%).
      These data justify the use of echocardiography in high risk newborns for the
      detection of congenital heart disease.

PMID- 9608997
TI  - [Obstructive ischemic involvement of the anterior descending coronary artery in
      asymmetrical septal form of hypertrophic cardiomyopathy].
AB  - PURPOSE: The significance of necrosis and fibrosis of the interventricular septum
      in hypertrophic cardiomyopathy (HCM) is controversial. The purpose of this study
      was then to evaluate the clinical impact of left anterior descending artery (LAD)
      disease in HCM. METHODS: Among 158 patients presenting with HCM, 6 (3.79%) had
      LAD disease. Mean age was 65.16 years (52 to 70), 4 were men and 4 had the
      obstructive form of HCM. All patients were submitted to complete clinical and
      laboratory evaluation. Mean time of the diagnosis was 141 months (ranging from 78
      to 182) for HCM and 42 months (ranging from one day to 106 months) for LAD
      disease. RESULTS: Five patients had unstable angina and one had myocardial
      infarction. LAD disease (60 to 100% coronary narrowing) was present in all
      patients; one patient had single vessel disease and 5 multivessel disease. During
      follow-up, 3 patients had coronary artery bypass grafting (CABG), one with
      associated septal myectomy; one was submitted to coronary angioplasty and 2 were
      submitted to medical treatment. During a follow-up period ranging from 76 to 124
      months after LAD disease diagnosis, one patient died. At the end of the study, a
      reduction of the thickness of the interventricular septum from 1.53 to 1.40 cm
      was observed and left ventricular outflow pressure gradient decreased from 56 to
      16 mmHg. Left ventricular diastolic diameter increased from 4.55 to 4.85 cm and
      systolic diameter from 2.83 to 3.13 cm. Left atrium diameter was unchanged.
      CONCLUSION: LAD disease is well tolerated in the asymmetrical form of HCM and may
      contribute to septal fibrosis, improving cardiac function. It does not represent
      an adverse factor in the evolution of HCM.

PMID- 9608998
TI  - [Long-term course and complications of arterial hypertension after heart
      transplantation].
AB  - PURPOSE: To evaluate the progression of arterial hypertension (AH) and its
      consequences, in patients submitted to cardiac transplantation (CT) in use of
      cyclosporine (CY). METHODS: In 65 patients submitted to orthotopic CT, we
      evaluated blood pressure, serum creatinine and blood levels of CY before, 15 and
      30 days, and 6, 12, 24, 48 and 60 months after CT; in 20 patients we analyzed
      cardiac index and systemic vascular resistance pre-CT, 15 and 30 days, 6 and 12
      months after CT; in 33 patients, we studied anatomic and functional modifications
      by echocardiography, 24 +/- 13 months after CT. RESULTS: Thirty days after CT, AH
      was present in 58.5% (50% mild), and after one year, 93% of patients were
      hypertensives (85% moderate-to-severe), remaining unchanged during the rest of
      follow-up. The serum creatinine progressively increased, reaching values
      significantly higher than those pre-CT after one year, persisting with a mild
      increment until 60 months. Echocardiography showed left ventricle hypertrophy in
      54% of patients, all of which had normal function. Two patients died as a direct
      consequence of hypertensive complications. CONCLUSION: AH in patients submitted
      to CT on CY use occurs early, increases in prevalence and severity during the
      follow-up and is mediated by an increase in vascular resistance. Also, the AH
      does not correlate to CY blood levels or nefrotoxicity, but it can impair renal
      function and compromise longevity of transplantation by inducing ventricular
      hypertrophy.

PMID- 9608999
TI  - [Blood pressure responses in children of normotensive and of hypertensive parents
      treated with pressor stimulus].
AB  - PURPOSE: To compare cardiovascular reactivity in adolescents with and without
      family history of hypertension. METHODS: Thirty two subjects, males, students,
      aging between 13 to 18 years old were examined. One half of them had no family
      history of hypertension and the other half had at least one hypertensive parent.
      Basal blood pressure level was obtained before the application of the following
      selected tests: isometric handgrip exercise test, cold pressor test and
      arithmetic mental stress test. The blood pressure values were obtained by a
      digital, oscilometric device, previously calibrated. RESULTS: The subjects with
      family history of hypertension exhibited higher basal levels of both systolic and
      diastolic blood pressure (p < 0.10). Concerning the tests applied, the subjects
      with family history of hypertension also exhibited higher responses, but only the
      responses of the diastolic blood pressure to the mental stress test was
      statistically significant (p < 0.10). CONCLUSION: Our findings point to the need
      of a special follow-up of children with a family history of hypertension.

PMID- 9609000
TI  - [Multicenter study of elderly patients assisted at outpatient cardiology and
      geriatrics clinics in Brazilian institutions].
AB  - PURPOSE: To evaluate epidemiological, clinical and therapeutic aspects of elderly
      patients with cardiovascular disease in Brazil. METHODS: Elderly patients with
      cardiovascular disease treated in 36 centers of cardiology and geriatrics were
      investigated through a questionnaire applied to those who had an appointment
      during the analyzed period. RESULTS: 2196 elderly patients ranging from 65 to 96
      years of age were analyzed, 60% of which were females. The main risk factors
      were: sedentarism (74%); high blood pressure (53%), high LDL-cholesterol (33%),
      high total cholesterol (30%), obesity (30%), low HDL-cholesterol (15%), diabetes
      (13%) and smoking (6%). A higher prevalence of females existed among those with >
      or = 3 risk factors. The main reason for the medical appointment was high blood
      pressure (48%). Stress test and coronariography were requested more often in
      males. The most common diagnoses were hypertension (67%), and coronary disease
      (29%). The most often used medications were diuretics (42%). CONCLUSION: There
      was high prevalence of risk factors (93%), mainly in females; sedentarism was the
      most common risk factor and prevalence increased with age; hypertension was the
      most common reason for a medical appointment. Diuretics were the most used drugs;
      congestive heart failure was the main disease associated to hospitalization (31%)
      and emergencies (10%).

PMID- 9609001
TI  - [Patent ductus arteriosus and pulmonary artery endarteritis].
AB  - We describe a seven year old girl with echocardiographic diagnosis of pulmonary
      artery endarteritis as a complication of a patent ductus arteriosus, confirmed at
      surgery. This case illustrates the necessity of complete surgical resection of
      the infectious source as a way to avoid other complications such as pulmonary
      embolism.

PMID- 9609002
TI  - [Surgical treatment of chronic pulmonary thromboembolism].

PMID- 9609003
TI  - [Antiatherogenic effects of endothelium-derived relaxing factor (nitric oxide)].

PMID- 9609005
TI  - [Successful reversal of pulmonary hypertension in Eisenmenger complex].

PMID- 9609004
TI  - [II Brazilian Consensus of Ambulatory Blood Pressure Monitoring].

PMID- 9609006
TI  - [Loyalty to common sense].

PMID- 9609007
TI  - [Medical treatment of heart failure at a tertiary hospital of Sao Paulo].
AB  - PURPOSE: To study how patients with heart failure (HF) are treated in a tertiary
      hospital in Sao Paulo. METHODS: One hundred patients with HF during ambulatory
      care were analyzed. Seventy-six were men, and the average population age was 56.8
      years old. All patients were submitted to echocardiogram, which identified
      ventricular diameters ranging between 48 and 89 mm (average 65.9) and ejection
      fraction (EF) between 0.22 and 0.59 (average 0.43). The cause of HF was ischemic
      in 42 cases, dilated cardiomyopathy in 28, valvular heart disease in 12, Chagas'
      disease in 10 and systemic hypertension in 8 patients. The prescribed treatment
      was analyzed, with attention to the prescription and dosage of angiotensin
      converting enzyme (ACE) inhibitors. We also analyzed whether the cause and/or the
      degree of HF influenced the treatment chosen. RESULTS: Eighty-seven patients
      received ACE inhibitors, 31 received doses below those recommended in the large
      trials. Digoxin was prescribed in 69 cases, diuretics in 85, and aspirin in 33.
      When dividing the patients according to EF, the group with EF below 0.45 was
      prescribed more often ACE inhibitors (91.5% vs 80.4%) and had more often usage of
      adequate doses (61% vs 48.7%). CONCLUSION: In this sample the majority of the
      patients were treated according to modern recommendations and tolerated well ACE
      inhibitors, however 1/3 did not receive ACE inhibitors in the recommended doses.
      Treatment based on betablockers or angiotensin II inhibitors were not routinely
      employed.

PMID- 9609008
TI  - [Role of myocardial contractile status and relaxation in ventricular dysfunction
      during the transition of heart hypertrophy to failure].
AB  - PURPOSE: To investigate the participation of contractile state and relaxation in
      cardiac muscle dysfunction during the transition from stable hypertrophy to
      cardiac decompensation in aging spontaneously hypertensive rats (SHR). METHODS:
      Isolated left ventricular papillary muscle function was studied in SHR with heart
      failure (SHR-F), in age-matched SHR without evidence of heart failure (SHR-NF),
      and in nonhypertensive controls Wistar-Kyoto rats (WKY). Muscles were analysed in
      isometric and isotonic contractions in Krebs-Henseleit solution with calcium
      concentration of 1.25 mM at 28 degrees C. RESULTS: Papillary muscles from SHR-F
      and SHR-NF demonstrated decreased active tension development and shortening
      velocity relative to normotensive WKY (p < 0.05). SHR-F and SHR-NF did not
      differ. Compared with SHR-NF and WKY, muscle passive stiffness was increased in
      the failing SHR (p < 0.05 versus WKY and SHR-NF). This parameter did not differ
      between SHR-NF and WKY (p > 0.05). CONCLUSION: These data suggest that the
      progression from stable hypertrophy to heart failure is associated with changes
      in the passive stiffness and is not related to depression of myocardial
      contractile function.

PMID- 9609009
TI  - [Athlete's heart in elite disabled athletes].
AB  - PURPOSE: To assess the prevalence of the athlete's, heart syndrome in elite
      disabled Brazilians athletes. METHODS: Seventy-five athletes, age 27.8 +/- 6.7
      years, 56 men, with various disabilities (47 physical, 12 visual and 16 cerebral
      paralysis) underwent clinical, electrocardiographic, vectorcardiographic,
      ergometric and echocardiographic evaluations. RESULTS: Athlete's heart signs
      occurred in 33% of the clinical evaluations, in 55% of the electrocardiograms, in
      15% of the vectorcardiograms, and in 5% of the echocardiograms. At least one of
      these signs was presented in 51% of the athletes. There were 2 or more
      abnormalities in 46% of the athletes and 4 or more signs in 12%. Exercise test
      was considered not ischemic in 77% of the subjects. There was right bundle branch
      block in 23% of the tests. CONCLUSION: There were two or more athlete's heart
      syndrome signs in 46% of Brazilian disabled athletes.

PMID- 9609010
TI  - [Natural history of myocardial hypertrophy and its association with
      hyperinsulinism in infants of diabetic mothers].
AB  - PURPOSE: To test the hypothesis that myocardial hypertrophy is associated with
      increased serum insulin levels in children of diabetic mothers and to determine
      the frequency and timing of this spontaneous regression. METHODS: Seventy-two
      patients were studied (54 children of diabetic mothers and 18 controls).
      Diagnosis of myocardial hypertrophy was made by fetal echocardiography. Amniotic
      fluid insulin levels were obtained from a previous prenatal study on hypertrophic
      cardiomyopathy, since the participation of the mothers was common to both
      projects. RESULTS: There were 10 cases of myocardial hypertrophy among children
      of diabetic mothers (18.52%). Septal thickness was significantly different
      between the 2 groups (children of diabetic mothers and controls) in the
      evaluation performed at the age of 1 month (p = 0.04). Insulin levels were still
      increased in children of diabetic mothers until the age of 3 months. During this
      period insulin levels were significantly higher than those of controls (p = 0.003
      and p = 0.001, at 1 and 3 months, respectively). The association between
      regression of ventricular septum thickness and the decrease of insulin levels
      occurred up to the age of 1 month. CONCLUSION: There was spontaneous regression
      of ventricular septum thickness in children of diabetic mothers during the first
      6 months of life. The association between hyperinsulinism and hypertrophic
      cardiomyopathy was present up to the first month of life.

PMID- 9609011
TI  - [Prevalence of dyslipidemias in adults in laboratory tests from Salvador,
      Brazil].
AB  - PURPOSE: To determine the prevalence of dyslipidemia in non-hospital laboratory
      tests of adults from Salvador, Brazil. METHODS: The study was carried out in
      subjects from a probabilistic sample of 25% of a total of 104 local laboratories
      that used the same enzymatic method for lipid analysis with the quality control
      as recommended by the Brazilian Society of Clinical Analyses. These represented
      93% of all non-hospital laboratories of Salvador in 1995. The odd months of 1995
      were selected for sampling in the present study. Criteria for dyslipidemias were:
      total cholesterol > or = 240; LDL > or = 160; HDL < 35 and triglycerides > or =
      200 mg/dl. Prevalence rates and their 95% confidence intervals (CI) and chi 2
      test were used in the analyses. RESULTS: Tests from two of the 26 laboratories
      were not used in the analyses due to file problems or refusal. 7,392 adults were
      screened, 65% female. We observed prevalence (95% CI) of hypercholesterolemia in
      30.0 (27.8; 32.2)%, high LDL in 30.1 (30.8; 35.4)% and hypertriglyceridemia in
      30.4 (29.0; 31.4)% of the females. As to the male subjects, prevalences were;
      24.0 (20.5; 27.5)% for hypercholesterolemia, 26.1 (22.4; 29.3)% for high LDL,
      27.6 (25.7; 29.5)% for hypertriglyceridemia. All gender differences were
      significant. Low HDL occurred in 15.9 (14.2; 17.8)% of males and in 8.0 (7.1;
      8.9)% of females. CONCLUSION: Dyslipidemia is an important risk factor observed
      in non-hospital laboratory tests of men and women in Salvador. Our data may
      provide physicians and other health care professionals with objective information
      to encourage life-style changes.

PMID- 9609012
TI  - [Use of high-dose oral amiodarone for the reversion of atrial fibrillation during
      the postoperative period of cardiac surgery].
AB  - PURPOSE: To report our experience using high dose oral amiodarone (1,800 mg/day)
      for the reversion of atrial fibrillation to sinus rhythm in patients submitted to
      cardiac surgery. METHODS: We retrospectively analyzed the records of 80 patients
      who had atrial fibrillation during the postoperative period after cardiac
      surgery, initially divided in two groups: group A, 28 patients that used
      amiodarone, and group B composed of patients receiving digoxin. The latter group
      was divided further in a third group (C), with 21 patients in which amiodarone
      was associated with digoxin if there was no reversion of the arrhythmia after 48
      hours of treatment. The observed differences were considered significant at P <
      0.05. RESULTS: Atrial fibrillation occurred in 19.4% of the patients submitted to
      surgery, predominating in males, 60 to 69 years-old. In group A there was
      reversion to sinus rhythm in 78.6% of the cases. In group B digoxin succeeded in
      60%, and in group C 90% of the patients reverted to sinus rhythm. CONCLUSION:
      High dose oral amiodarone, alone or combined to digoxin, can be safe and
      effective for the treatment of atrial fibrillation after cardiac surgery.

PMID- 9609013
TI  - [Infective endocarditis in adolescents. Analysis of risk factors for hospital
      mortality].
AB  - PURPOSE: To study the epidemiological, clinical, therapeutic and evolutive
      aspects of endocarditis in a group of patients aging 12 to 20 years-old (mean
      15.5). METHODS: Thirty-three consecutive patients (14 males, 19 females) admitted
      with infective endocarditis were retrospectively studied. RESULTS: Infective
      endocarditis mortality was 42%. Rheumatic heart disease was the predominant
      underlying condition in 63% of patients. Congenital heart disease (24%) and
      cardiac prosthesis (12%) were the other affections involved. The majority of
      patients (78%) were in functional class III and IV, with more deaths than the 22%
      who were in functional class I and II (p = 0.01). Staphylococcus aureus was the
      most frequently isolated agent (42% of the positive blood cultures, followed by
      Staphylococcus viridans, 21%). Multivariate analysis identified total leukocyte
      count above 10,000/mm3 and functional class, both at admission (p = 0.01 and p =
      0.004, respectively), and the occurrence of embolic complications (p = 0.03) as
      independent predictors of in-hospital mortality. CONCLUSION: Rheumatic heart
      disease remains, as in adults, the main predisposing factor for infective
      endocarditis in adolescents, and S. aureus is, like in children, the leading
      agent. Mortality is high and functional class at hospital admission, embolic
      complications and leukocytosis are independent predictors of in-hospital
      mortality.

PMID- 9609014
TI  - [Assessment of left internal thoracic artery anastomosis with left anterior
      descending coronary artery by Doppler echocardiography].
AB  - PURPOSE: To study the value of Doppler echocardiography as a tool for the
      evaluation of left internal thoracic artery graft (LITAG) patency in patients who
      underwent coronary revascularization using minimally invasive bypass surgery
      without extracorporeal circulation. METHODS: The first 12 consecutive patients
      were studied after coronary artery bypass surgery using a 5 MHz Doppler
      transducer. Doppler signals for the systolic and diastolic flow velocities were
      preferably obtained in the second intercostal space. All patients underwent
      coronary angiography while hospitalized. RESULTS: The exam was feasible in 93% of
      patients. Doppler flow pattern was predominantly diastolic (pattern A) in
      patients with patent anastomoses (6/7). In patients with occluded anastomoses
      (4/4) Doppler flow pattern was predominantly systolic (pattern B) (p = 0.003).
      CONCLUSION: Internal thoracic artery flow pattern as measured by Doppler
      echocardiography after minimally invasive coronary artery bypass graft surgery is
      an accurate method for identifying LITAG patency.

PMID- 9609016
TI  - [Anatomo-clinical correlation (case 7/97--Hospital Santa Isabel--Cenprecor-
      Salvador, BA, Brazil)].

PMID- 9609015
TI  - [Acute left ventricular systolic dysfunction after pericardial effusion
      drainage].
AB  - A patient with a thymoma and initially normal ventricular systolic function
      developed cardiac tamponade, which was relieved by pericardiocentesis. After four
      days, the tumor was removed and, one week after the relief of tamponade, she
      developed severe left ventricular systolic dysfunction, that recovered in three
      days with venous therapy.

PMID- 9609017
TI  - [Declaration of early defibrillation].

PMID- 9609018
TI  - [Proposal of a new standard for the nutritional assessment of pregnant women].
AB  - BACKGROUND: There is evidence to suggest that the criteria for nutritional
      assessment of pregnant women, used by the Chilean Ministry of Health,
      overestimates nutritional disturbances. AIM: To propose a new reference table to
      assess the nutritional status of pregnant women, based on body mass index.
      MATERIAL AND METHODS: The table was theoretically defined using criteria for
      normality proposed by FAO and the weight increase during pregnancy that is
      associated with a lower maternal and fetal morbidity and mortality. In 665
      pregnant women, weight, height, mid arm circumference and skinfolds were measured
      using standard techniques. Body mass index, arm fat and muscle area and
      percentage of body fat were calculated. Body composition for each nutritional
      category, derived from the body mass index or "Rosso-Mardones classification",
      was analyzed. RESULTS: According to the new table, under weight women had lower
      percentage of body fat and mid arm circumference and overweight women had higher
      weight, skinfold thickness and percentage of body fat than the homologous groups
      defined according to Rosso-Mardones tables. CONCLUSIONS: The proposed reference
      table may be useful to correct distortions generated by the current norms for
      nutritional assessment of pregnant women, proposed by the Chilean Ministry of
      Health. It has to be validated, analyzing its sensitivity, specificity and
      predictive value to predict fetal and maternal variables.

PMID- 9609019
TI  - [Design of a weight gain chart for pregnant women].
AB  - BACKGROUND: A low weight for height of pregnant women at the start of pregnancy
      and a low weight gain during pregnancy has a negative impact of fetal growth.
      AIM: To report the design of a weight gain chart for pregnant women that allows
      to classify mothers according to their nutritional status and to monitor weight
      gain during gestation. MATERIAL AND METHODS: Data from 1745 Chilean mothers who
      delivered their newborns in 1983 and 1984 were used to build this chart. RESULTS:
      The instrument could diagnose, from gestational week 10 onwards, mothers at risk
      of delivering babies with birth weight under 3000 g and set weight gain goals for
      each individual mother based on her nutritional status. Similarly, mothers at
      risk of delivering babies with birth weight over 3999 g could be early diagnosed
      during pregnancy and guided to have a prudent weight gain. CONCLUSIONS: The chart
      can be easily used in prenatal clinics of developing countries and is currently
      applied in several Latin American countries.

PMID- 9609020
TI  - [Transplacental alloimmunization against specific platelet antigens: prevalence
      and features in a Chilean population].
AB  - BACKGROUND: Neonatal alloimmune thrombocytopenia (NAIT) is a result of
      fetomaternal incompatibility. Platelet destruction is caused by a maternal
      antibody directed against a fetal platelet antigen inherited from the father and
      lacking on the mother's platelets. The incidence and features of transplacental
      alloimmunization depend on the frequency of expression of platelet specific
      antigens; which are highly variable among different populations. AIM: To
      determine the prevalence and characteristics of transplacental alloimmunization
      in a large group of pregnant women in Chile. MATERIAL AND METHODS: We studied
      3,041 samples obtained during the third trimester of gestation. In all samples,
      anti platelet antibodies were screened by ELISA with platelet membranes fixed to
      a microtiter plate. Positive samples were further studied for antigenic
      specificity with the monoclonal antibody specific immobilization of platelet
      antigens (MAIPA) test. RESULTS: Anti platelet antibodies were found in 261
      samples (8.5%). The MAIPA test identified 6 samples with antibodies directed
      against major platelet membrane glycoproteins, 2 anti GPIb, 2 anti GPIIb/IIIa and
      2 anti GPIa/IIa. In four cases, anti HLA antibodies coexisted. Two cases
      corresponded to well defined platelet antigen systems: one anti HPA-1a and one
      anti HPA-5b. No clinical evidence of thrombocytopenia of the newborn was detected
      in all these cases with anti GP antibodies. CONCLUSIONS: A prevalence of platelet
      specific antibodies of 0.2% with only one anti HPA-1a was detected. These
      findings are in contrast with those of other populations but in accordance with
      the low frequency of the HPA-1 b/b phenotype in the Chilean population. The very
      low incidence of platelet specific antibodies and the lack of association with
      clinical thrombocytopenia in the newborn, do not support the recommendation of
      routine antenatal screening to all women in Chile.

PMID- 9609021
TI  - [Effects of metformin on insulin resistance in obese and hyperandrogenic women].
AB  - BACKGROUND: Metformin is a biguanide often used in obese diabetics that improves
      tissue sensitivity to insulin. AIM: To assess the effects of metformin on tissue
      insulin sensitivity in obese and hyperandrogenic women. PATIENTS AND METHODS:
      Eight obese and eight obese and hyperandrogenic women received metformin 850 mg
      orally during 12 weeks. Before and at the end of the treatment period, an insulin
      tolerance test to measure insulin sensitivity was performed and blood was drawn
      to measure sex hormone binding globulin (SHBG), dehydroepiandrosterone sulphate
      (DHEAS), testosterone, triglycerides, total and HDL cholesterol. The free
      androgen index was calculated for each sample. RESULTS: After metformin
      treatment, the insulin sensitivity index improved from 0.38 (0.05-0.5) to 0.43
      (0.25-0.59) in obese women and from 0.2 (0-0.36) to 0.3 (0.06-0.4) in obese and
      hyperandrogenic women. SHBG increased and total cholesterol and triglycerides
      decreased significantly in both groups. No other significant changes were
      observed. CONCLUSIONS: Metformin has a favorable effect on tissue sensitivity to
      insulin, SHBG and serum lipids in obese and hyperandrogenic women.

PMID- 9609022
TI  - [Ethical features related to clinical decisions in neonatology. Preliminary
      study].
AB  - BACKGROUND: Personnel working in neonatal intensive care units frequently face
      difficult ethical problems related to the initiation, maintenance or withdrawal
      of life support therapies. AIM: To assess the importance of ethical issues in the
      clinical decision making of health care providers in neonatal intensive care
      units. MATERIAL AND METHODS: A questionnaire based on five clinical vignettes
      that assessed judgments about quality of life, impact of parent's opinions and
      decision making in emergency situations and with different degrees of certainty,
      was designed. Eleven neonatologists and 20 nurses and midwives specialized in
      neonatology anonymously answered this questionnaire. RESULTS: There was a great
      inter individual variability in therapeutic approaches in cases with a bad vital
      and neurological prognosis. In cases of medical emergencies with uncertain
      diagnoses, bad vital prognosis but neurological indemnity, most professionals
      coincided in delivering all possible therapeutic options. Parent's opinions had a
      great impact in medical decisions, except when there was neurological indemnity.
      CONCLUSIONS: The specific responsibilities of the different agents in medical
      decision making must be delimited. Parents do not have absolute rights over their
      offspring and physicians must reject useless therapies.

PMID- 9609023
TI  - [Rotational atherectomy (Rotablator) for percutaneous transluminal coronary
      angioplasty].
AB  - BACKGROUND: The use of Rotablator in percutaneous transluminal coronary
      angioplasty attempts to reduce the atheromatous plaque abrading it and
      fragmenting the parietal calcium of the artery. AIM: To report our experience
      with the use of Rotablator. PATIENTS AND METHODS: Rotational atherectomy was
      performed in 189 patients aged 60.8 +/- 11 years (154 men). The clinical
      indication for the procedure was chronic angina in 22%, unstable angina in 44%,
      myocardial infarction in 21%, silent angina in 7% and re-stenosis in 6%. One
      hundred seventy seven patients were followed for a mean of 15.9 +/- 6.3 months.
      RESULTS: Two hundred thirty six stenoses in 215 coronary arteries were treated
      with a 98.7% angiographic success rate. One patient had a Q infarction and no
      patient died or required emergency surgery. Fourteen patients had rises in CK MB
      enzymes (non Q infarction). Three patients had a pseudoaneurism and three had
      bleedings that required transfusion. Of the followed patients, 33 had a
      clinically suspected re-stenosis, that was angiographically confirmed in 23.
      Cardiac mortality was 2.3%. Seventy nine percent of patients had an evolution
      without angina or coronary events. CONCLUSIONS: Percutaneous transluminal
      coronary angioplasty with the use of Rotablator had a high immediate success rate
      and a low incidence of complications. The clinical evolution of patients has been
      favorable with a low incidence of mortality and ischemic events.

PMID- 9609024
TI  - [Universal Declaration on the Human Genome and Human Rights].

PMID- 9609025
TI  - [Bioethics in contemporary medicine].
AB  - Bioethics arose in a delicate social and political moment in the United States of
      America. With time, it has become a social and perhaps political movement. Its
      scope is wider and different than that of medical ethics. Bioethics appeared in
      the second half of the twentieth century, in the middle of a spectacular advance
      in biological knowledge and technology. Meanwhile, medical ethics was formulated
      in the fifth century B.C. in relation to medical care. This defines the main
      focus of their respective interests. Anglo-Saxon philosophers, deriving from
      moral philosophy, applied the principles of beneficence, no maleficence, justice
      and autonomy to medicine. The Hippocratic oath refers specifically to the first
      three and to a number of other ethical principles. Nothing in its contents,
      contradicts the principle of autonomy. The emphasis in the principle of autonomy
      that some specialists in bioethics pose, even over the principle of beneficence,
      is determined, according to our judgment, by inherent factors of the North
      American culture. We believe that medical ethics should be distinguished even
      though not separated from bioethics. Physicians should go back to the Hippocratic
      oath as the fundamental guide for their professional activity.

PMID- 9609026
TI  - [Beginning of human life. The need for a philosophical reflection].
AB  - The question about the identification of the exact moment when human life begins
      has a special ethic transcendence. Elements afforded by science are insufficient
      for this objective, because of the nature of the object in study and of the
      cognoscent subject. This article makes a proposal with arguments afforded by the
      philosophical reflection.

PMID- 9609027
TI  - [Reflections on the beginning of a new human individual].
AB  - Although there is very little doubt that when a child is born a new actual person
      can be identified, there is continuous debate as to the moment in embryological
      development when that same person begins its existence. Based on today's
      knowledge of human fertilization and the early stages of embryo development, this
      position paper examines three theses that deal with the establishment of
      personhood. The first thesis stipulates that a human individual exists prior to
      syngamy. Although the sperm has penetrated the plasmatic membrane of the oocyte,
      the genetic information contained in both gametes remain separated in the male
      and female pronucleus; thus, the oocyte contains the sum of two identities
      responsible for creating a new individual. This paper will argue that a human
      individual has not yet formed. The second thesis recognizes that with syngamy, a
      unicellular structure (zygote) is established, endowed with genetic individuality
      and with the potential to become a person maintaining that same genetic framework
      throughout its lifetime. The third thesis argues that although genetic
      individuality is established with syngamy, the ontological individuality is only
      reached once genetic expression and cellular specialization are achieved and
      twinning is no longer possible (15 days after fertilization).

PMID- 9609028
TI  - [Medical liability and unintentional offenses in professional practice].
AB  - Malpractice and negligence lawsuits against physician have significantly
      increased lately. Therefore, the legal and ethical setting of this problem in our
      country must be specified. There are multiple causes that lead to attribute the
      responsibility of a determinate damage to medical practice, but the most
      important is an inadequate medical-patient-family relationship. Lawsuits are
      transcendental for physicians and affect them in several ways. Several measures
      are proposed to reduce them. Considering the increasing importance of solidarity
      and shared compensations, the responsibility of institutions and other
      professionals, besides physicians, is analyzed.

PMID- 9609029
TI  - [The care of the terminally ill patient].
AB  - Drs. Alejandro Goic (internist), Ramon Florenzano (psychiatrist), Bernardino
      Pinera (physician and Catholic Bishop), Sergio Valdes (internist) and Rodolfo
      Armas (internist) participated in a round table about the care of the terminally
      ill, during a Postgraduate Course organized by the Chilean Society of
      Gastroenterology. After a general introduction, participants discussed the
      psychological aspects of terminally ill patients, about the sense of death from a
      Christian anthropological perspective, the terminally ill in intensive care units
      and finally about the education of medical students in this frequently neglected
      aspect of medical practice.

PMID- 9609030
TI  - [Adverse drug reactions among hospitalized elderly patients. Prospective study].
AB  - BACKGROUND: It is not clear if old age is a risk factor for adverse drug
      reactions. AIM: To study the incidence of adverse drug reactions and the effect
      of age in patients admitted to an Internal Medicine Service in an university
      hospital. PATIENTS AND METHODS: Two hundred one patients, hospitalized at the
      Clinical Hospital of the Catholic University, were studied. These patients were
      followed using a prospective pharmacological surveillance method. For statistical
      purposes, patients aged 65 years old or older were compared with those younger
      than 65 years old. RESULTS: Patients over 65 years old had a 33% incidence of
      adverse drug reactions, mainly involving cardiovascular system and provoking
      metabolic disturbances. Younger subjects had a 24% incidence of adverse drug
      reactions, mainly involving the gastrointestinal system and the skin. Sixteen
      percent of adverse drug reactions were classified as severe and there was a
      direct relationship between its frequency and the number of drugs prescribed, the
      hospitalization length and the presence of renal failure. Younger patients with
      adverse drug reactions had lower serum albumin levels than those without adverse
      reactions. This relationship was not observed in older patients. CONCLUSIONS: The
      frequency of adverse drug reactions in hospitalized patients, is related to the
      number of drugs prescribed and the length of hospitalization.

PMID- 9609031
TI  - [Chronic exposure to environmental lead in Chilean infants].
AB  - BACKGROUND: In Chile, there are several sources of environmental lead exposure.
      However, the few studies about lead levels in Chilean infants, do not allow to
      establish the prevalence of high lead levels in this population. AIM: To measure
      blood lead levels in nursing infants, living in rural and urban areas, from birth
      until two years of age. SUBJECTS AND METHODS: Newborns from public maternity
      hospitals in Santiago and a rural area were selected for the study. An umbilical
      cord blood sample was obtained at birth and venous blood samples thereafter,
      every 6 months until the age of 24 months. Lead levels were measured by atomic
      absorption spectrophotometry. Atmospheric lead was measured simultaneously every
      week in Santiago and the rural area. RESULTS: Three hundred twelve children from
      Santiago and 113 from the rural area completed the 24 months follow-up. The mean
      lead exposure for infants living in Santiago and in the rural area was 1.23 +/-
      0.66 and 0.19 +/- 0.15 micrograms/m3 respectively (p < 0.001). Mean blood levels
      were always higher in infants from Santiago, compared to those from the rural
      area. At 24 months, 4.5% of children from Santiago and 0.7% of children from the
      rural area had blood lead levels over 10 micrograms/dl. Significant risk factors
      for high lead levels were recent painting of the house where the infant lives,
      eating soil, biting banisters and familiar labor exposure to lead. CONCLUSIONS:
      Infants living in an urban area and exposed to increased atmospheric lead levels
      have higher blood lead levels than infants living in a rural area.

PMID- 9609032
TI  - [Respiratory symptoms and cough reflex in populations exposed to different
      degrees of environmental pollution].
AB  - BACKGROUND: Santiago is a city with a high degree of environmental pollution
      caused by particulate matter and ozone, producing adverse effects in the
      respiratory system. AIM: To compare respiratory symptoms and cough reflex in
      adults from Santiago and from a rural area with low levels of environmental
      pollution. SUBJECTS AND METHODS: One hundred twenty six non-smoker adults from
      Santiago and 116 from a rural area with low levels of pollution answered a
      respiratory symptom questionnaire. Of these 101 subjects from Santiago and 116
      from the rural area inhaled doubling concentrations of capsaicin from 0.5 to 500
      microM or until five coughs were elicited. The lowest concentration eliciting 2
      or more coughs (CD2) or 5 or more coughs (CD5) was recorded. Levels of
      environmental particulate matter were also recorded in both locations. RESULTS:
      Levels of particulate matter were 102 +/- 41 and 64 +/- 24 micrograms/m3 in
      Santiago and the rural area respectively. People from Santiago had higher rates
      of throat clearing, cough and phlegm. CD2 geometric mean and confidence limits in
      Santiago and the rural area were 6.9 (5.2-7.4) and 2.8 (2.7-2.9) respectively (p
      < 0.001). No differences in CD5 were observed between both locations.
      Multivariate analysis disclosed the variable location (city) as the only
      independent predictor of respiratory symptoms. CONCLUSIONS: The increased CD2
      found in Santiago suggests that the higher rates of respiratory symptoms related
      to air pollution can be associated to a decreased sensitivity of the cough
      reflex.

PMID- 9609033
TI  - [Antibiotic effect of wild Streptomyces strains isolated from Chilean soils].
AB  - BACKGROUND: The soils of the southern part of Chile, that are isolated, cold,
      humid, poorly oxygenated and with a low acidity, could contain new strains of
      antimicrobial producing Streptomyces. AIM: To demonstrate that the soil of the
      Southern region of Chile contains Streptomyces strains with antimicrobial
      activity towards pathogenic bacteria and fungi. MATERIAL AND METHODS: Two hundred
      fifty eight soil and sediment samples were collected from 148 places in Southern
      regions of Chile. They were cultured in Kuster-Williams growth media and the
      presence of Streptomyces was confirmed by microscopic examination and biochemical
      characterization. The antimicrobial activity against reference microorganisms of
      each wild strain was tested using the disk method. Among active Streptomyces
      strains, 38 with the higher activity were selected and tested against 142
      clinical microorganisms. RESULTS: Seventy seven percent of soils were positive
      and 542 wild strains of Streptomyces were isolated; of these, 266 had
      antimicrobial activity. Fifty three percent of isolates had activity against S
      aureus 43% against B subtilis and 0.7% against E coli. Most Streptomyces were
      active against more than one organism. When there was activity against single
      organisms, these were mostly eucariotic, such as C albicans and T mentagrophytes.
      Among clinical microorganisms, 29% of S aureus strains were inhibited, while P
      aeruginosa, Alternaria sp, P vulgaris and Y enterocolitica strains were not
      inhibited. The most frequent Streptomyces morphotypes were those showing
      pigmented colonies with flexuous and spiral shaped chains of arthrospores.
      CONCLUSIONS: Soils of the Southern region of Chile allow the growth of abundant
      native strains of Streptomyces with a promising antimicrobial activity.

PMID- 9609034
TI  - [Chlamydia trachomatis infection in asymptomatic Chilean men and with urethritis.
      Usefulness of first catch urine samples].
AB  - BACKGROUND: Chlamydia trachomatis is responsible for 30 to 50% of genital tract
      infections and is present, without symptoms, in 20% of men and 60% of women. We
      have little information in Chile about the prevalence of this infection. AIM: To
      assess the prevalence of Chlamydia trachomatis in men, using first catch urine
      samples. SUBJECTS AND METHODS: Three hundred and fifty one first catch urine
      samples of asymptomatic men and 50 samples coming from men with a primary
      urethritis, were analyzed. Urethral discharge samples from the latter were
      simultaneously studied. Analysis was performed using an enzyme immuno analysis
      (MicroTrak Chlamydia EIA, Syva Co.) and a nested polymerase chain reaction
      towards the gene that codifies MOMP (PCR/OMP). RESULTS: Among asymptomatic men,
      two of 154 teenagers aged 18 to 19 years old (1.3%), 10 of 100 university
      students (10%) and eight of 97 adults over 30 years old (8.2%), were infected.
      The global prevalence of infection in these men was 5.7%. The prevalence of
      infection in men with urethritis was 12%. Urine EIA had a higher detection
      frequency than PCR/OMP, but according to another PCR assay, these results were
      false positives. EIA in first catch urine, had a sensitivity, specificity,
      positive and negative predictive value of 83.3, 75, 31.3 and 97% respectively,
      for the detection of Chlamydia trachomatis. The figures for PCR/OMP were 100% for
      all these parameters. CONCLUSIONS: The prevalence of Chlamydia trachomatis
      infection in Chilean men is similar to that reported in developed countries.
      Enzyme immuno assay in first catch urine had a good diagnostic accuracy and could
      be used in epidemiological studies in asymptomatic men.

PMID- 9609035
TI  - [Clinical correlation between the premortem study and autopsy].
AB  - BACKGROUND: Lately, autopsies are performed less frequently in hospitals, despite
      their importance as a diagnostic tool. AIM: To study the concordance between
      clinical diagnosis and postmortem study in patients that died in a teaching
      hospital. MATERIAL AND METHODS: Autopsy findings in 57 patients (aged 16 to 85
      years old, 28 female) that died at a University hospital were analyzed. Clinical
      diagnoses were compared with those of the postmortem examination and the degree
      of concordance between both diagnoses was calculated. RESULTS: Seven major
      omissions (12.3%), whose knowledge could have changed the clinical course of
      patients, were detected. These omissions occurred in patients with complex
      diseases or due to limitations of diagnostic procedures. Also, seven omissions,
      found in severely ill patients, whose knowledge would not change the patient's
      evolution, were also detected. CONCLUSIONS: Autopsy still is a valuable tool to
      assess the quality of care for patients that die during their hospitalization.

PMID- 9609036
TI  - [Determination of DNA content in salivary gland tumors].
AB  - BACKGROUND: DNA content determination is a useful tool in the characterization of
      different malignant tumors. AIM: To measure DNA content in cells of salivary
      gland tumors as adjunct to histological diagnosis, correlating morphologic and
      biological features of these tumors. MATERIAL AND METHODS: From the archives of
      the Pathology service of a general hospital, 21 salivary gland tumors, 15
      pleomorphic adenomas, 3 mucoepidermoid carcinomas and 3 cystic adenoid carcinomas
      were selected. DNA content was determined in the histological samples using a
      flow cytometric DNA analysis. RESULTS: All pleomorphic adenomas had a normal or
      diploid DNA content. Fifty percent of malignant tumors had an aneuploid DNA
      content (1 mucoepidermoid carcinoma and 2 cystic adenoid carcinomas).
      CONCLUSIONS: DNA determination may help in the histological diagnosis of salivary
      gland tumors. The presence of aneuploidy suggests malignity.

PMID- 9609037
TI  - [Parathyroid scintigraphy with Tc99m Sestamibi].
AB  - BACKGROUND: Parathyroid scintigraphy with Tc99m Sestamibi, a tracer that is taken
      up by hyperfunctioning parathyroid tissue, has a high yield in the diagnosis of
      abnormal parathyroid growths. AIM: To assess the usefulness of parathyroid
      scintigraphy with Tc99m Sestamibi in patients with suspected hyperparathyroidism.
      PATIENTS AND METHODS: We analyzed retrospectively 29 patients with suspected
      hyperparathyroidism, in whom a scintigraphy with Tc99m Sestamibi was performed.
      RESULTS: Twenty four of 25 patients in whom hyperfunctioning parathyroid tissue
      was evidenced with scintigraphy, were operated. Histological diagnosis of the
      excised parathyroid gland, showed 23 adenomas and 1 hyperplasia. Anatomical
      location disclosed by scintigraphy was concordant with surgical findings in all
      cases, including a mediastinic adenoma. Of the four patients with negative
      scintigraphic findings, two had transitory PTH elevations and in two the presence
      of adenoma or hyperplasia could not be demonstrated with other diagnostic
      procedures. CONCLUSIONS: Parathyroid scintigraphy with Tc99m Sestamibi had an 86%
      sensitivity for the detection of hyperfunctioning parathyroid tissue in patients
      with elevated PTH.

PMID- 9609038
TI  - [Diffuse lung involvement in primary amyloidosis as an infrequent cause of
      interstitial lung disease. Clinical case].
AB  - We report a 50 years old female, admitted to the hospital due to malaise lasting
      7 months, with diffuse bilateral lung infiltrates and a progressive respiratory
      insufficiency, dying one month after admission. A transbronchial biopsy disclosed
      an extensive amyloid infiltration. The necropsy confirmed this finding and showed
      a systemic primary amyloidosis associated to a multiple myeloma.

PMID- 9609039
TI  - [Supraventricular paroxysmal tachycardia with ventriculo-atrial dissociation.
      Report of one case].
AB  - Nodal reentrant supraventricular paroxysmal tachycardia corresponds to a reentry
      circuit established between fibers with different conduction velocities and
      refractory periods in the atrioventricular node. These are the slow and fast
      nodal pathways. That ventricular tissue does not form part of the circuit of this
      arrhythmia is accepted nowadays, and the involvement of atrial tissue is
      discussed. We report a 57 years old male with a nodal reentrant tachycardia. In
      the electrophysiological study he presented an atrial and ventricular
      dissociation during the tachycardia. These findings allow a better understanding
      of the electrophysiological substrate of this arrhythmia.

PMID- 9609040
TI  - [Anal tuberculosis. Report of a case].
AB  - We report a 70 years old man presenting with malaise, anal pain and progressive
      defecation difficulty, with a decrease in stool caliber. The patient had no
      contact or past history of tuberculosis. On physical examination, there was an
      ulcerated anal lesion with purulent discharge, that produced an anal stenosis.
      The patient had an erythrocyte sedimentation rate of 108 mm/h, images of active
      tuberculosis in both apical pulmonary lobes and a chronic tuberculous
      inflammation with caseation and epithelioid tubercles was observed in a biopsy of
      the anal lesion. Treatment with antituberculous drugs produced a categorical
      remission of anal lesions and after five months of therapy the patient is well.

PMID- 9609041
TI  - [Bioethical dimensions of medical care in the elderly].
AB  - This editorial examines the challenges posed by the current epidemiological
      transition towards ageing of societies, against the background of medical
      technologies: life-saving, life-sustaining and life-enhancing. Increased life
      expectancy among the elderly, compression of morbidity in the last year of life,
      cost containment in health-care delivery and humane treatment are elements of the
      dilemma facing modern medicine confronted to the aged. Technical success and
      medicalization of life are doomed to failure if the necessary reflection on what
      is proper, what is good and what is fair or just is not incorporated into
      everyday practice. These bioethical dimensions' should be reformulated at the
      level of the individual professional, the institutional environment and the
      social milieu. Aside from gloomy predictions about the future, the challenges
      imposed by treatment of the elderly are seen as invigorating stimuli for the
      continuous improvement of medical care.

PMID- 9609042
TI  - [The situation of the elderly in Chile].
AB  - Chile is experiencing a demographic transition and the causes of death and
      diseases of elders are similar to those of developed countries. However, these
      facts do not reflect the real problems that elderly people must face in this
      country, since they frequently suffer of not well diagnosed or assessed chronic
      diseases or functional limitations, that render them dependent or prostrated. If
      Chile wants to improve the physical and mental well being of elders, a global
      policy towards them must be developed and the financing of health services must
      be assured. In March 1996, a National Policy for Elderly People, aiming to
      improve the quality of life of these individuals, was approved by the government.
      We must successfully prevent and retard functional impairment and divulge the
      integral geriatric focus, encouraging global assessment, preventing disabilities
      and protecting functional independence. We must develop specialized Geriatric
      services in general hospitals, day care centers and rehabilitation units. We must
      teach the general principles of geriatric practise to health teams. Chile has a
      few trained specialists in geriatric medicine that must train other
      professionals. Thus, Medical Schools should expand research and post graduate
      training programs in geriatrics.

PMID- 9609043
TI  - [Why do we work in public hospitals? Some ideas to keep in mind].
AB  - Why do we work in public hospitals, what do we look for and what do we find
      working at these places? There are several answers. The heritage, the places
      where we learnt, the places where medicine is practiced. A model that feeds us.
      They cannot be improved and it is difficult to accept their limitations. However,
      many factors such as teaching, research and group work, encourage us to continue
      working in them. Variation and simultaneity, they are places with many variables,
      a living organism. The myth, the mother, that transmits its principles and
      behaviors, gives us a sense of life, feeds us and allows us to feed others.
      Economical reasons and performance. When performance of physicians is analyzed,
      positive values such as contact with patients, hours of discussion and study,
      quality of care, risks, dedication and training difficulties must be taken into
      consideration. Hospitals are not a patient assembly line. Fantasies and
      representations. We are participating in a health community and hospitals become
      a place for personal growth. Respect towards poverty. Helping the less fortunate.
      Knowledge and learning. Experiencing values. Forgotten words. Bioethics brought
      back several principles that are present in hospitals such as compassion,
      empathy, sweetness, service, humility, gratitude.

PMID- 9609044
TI  - [The problem of obesity and its shocking characteristics in Chile].
AB  - Obesity is a disease which severely affects health associated to an increase in
      relative mortality. The measurement of obesity is currently performed by means of
      the Body Mass Index (BMI). Normal BMI values are between 20 and 24.9 kg/m2. In
      obese individuals a central fat distribution is associated with an increased
      mortality in men and probably in women when compared with a peripheral
      distribution. Based on studies carried out in the Metropolitan Region (Greater
      Santiago) in 1992, it is estimated that the prevalence of obesity in the
      population is near 20% in men and 40% in women, with the highest prevalence being
      observed in women from a low socioeconomic level. The projection of these figures
      to the whole country gives an estimate of 2.5 million people in Chile with an
      increased risk of mortality due to obesity. Since there is a lack of awareness in
      the Chilean population of the pathology of obesity and its consequences, the
      implementation of programs of prevention and treatment of this disease lead by
      the health authorities is of paramount importance.

PMID- 9609045
TI  - [Infant mortality in Chile: the great descent].
AB  - Infant mortality in Chile decreased from 120 to 12 per thousand between 1960 and
      1994. Outstanding events of this "great descent" are reviewed, based on past
      research and on updated information. Demographic and socioeconomic changes and
      improvements in health care that occurred during this period of decline are
      shown. It is estimated that 30% of the reduction of infant mortality between 1972
      and 1982 was due to the decreasing proportion of births of high mortality risk,
      as a consequence of the fertility decline initiated in the mid 60s. Possible
      explanations for the continuing decline of infant mortality during the economic
      crisis of 1975 and 1982 are discussed. Finally, neonatal and postneonatal
      mortality rates by causes are compared between 1994 and 1980 and causes of death
      in extreme groups of infant mortality differentials by age of mother, birth
      order, gestational age, place of residence and educational level of the mother
      are shown.

PMID- 9609046
TI  - [Trends in birth rates, general, infantile and neonatal mortality in Chile from
      1850 to date].
AB  - BACKGROUND: Chile has experienced great changes in its health conditions, due to
      economical, social and demographic phenomena. AIM: To underline the moment of the
      demographic transition in Chile by means of a chronological epidemiological
      study, using available information. MATERIAL AND METHODS: Data was obtained from
      registries of the National Statistical Office, General Statistics Direction and
      National Institute of Statistics. RESULTS: Birth rate was 41/1000 in 1850,
      remained stable until the thirties, decreased to 35/1000 in 1965, to 21.3/1000 in
      1978 and to 20.5/1000 in 1994. The mortality rate increased from 20.3 to 37/1000
      from 1850 to 1901 and the it descended to 5.50/1000 in 1993. The annual
      population growth was 1% in the forties, increased to 2.5% in 1965 and is 1.6% at
      the present. The population thus increased from 1,400,000 inhabitants in 1850 to
      14,000,000 in 1994. The nuptial rate has remained between 7 and 8/1000 since
      1934. Infantile mortality was 337 per 1000 newborns in 1950 and dropped to 12 in
      1994. It represented 36% of the total mortality until the sixties, and now
      represents only 5%. This has contributed to the increase in life expectancy and
      ageing of our population. Neonatal mortality dropped from 136 per 1000 newborns
      in 1915 to 6.8 in 1994. Fetal mortality changed from 50 per 1000 newborns in 1936
      to 5.3 in 1993. CONCLUSIONS: Several causes have contributed to the changes in
      the above mentioned indicators. Currently, we are in the third stage of a
      Demographic transition that began in the sixties.

PMID- 9609047
TI  - [Cloning of internal medicine: are we experiencing it?].

PMID- 9609048
TI  - [Improving the editing of medical journals and the World Association of Medical
      Editors (WAME)].
AB  - Medical journal editing is a task with many facets. The role of the editors
      includes organizing and evaluating a peer-review system as a main tool for their
      decision making in selecting manuscripts to be published. The International
      Congress on Biomedical Peer Review and Global Communications was held in
      September, 1997, in Prague, Czech Republic, organized by JAMA, the BMJ and
      Project HOPE, and sponsored by several other organizations. A meeting of the
      World Association of Medical Editors took place during this Congress and its
      institutional objectives and membership were discussed and enlarged, based on the
      previous foundation Conference held in Bellagio, Italy, in March 1995. The main
      goals of this Association: "To facilitate worldwide cooperation and communication
      among editors of peer-reviewed medical journals; to improve editorial standards,
      to promote professionalism in medical editing through education, self-criticism
      and self-regulation; and to encourage research on the principles and practices of
      medical editing" were accomplished in a warm and friendly atmosphere, with over
      300 participants from 46 countries and every continent. Revista Medica de Chile
      was represented in these meetings by its former and present Editors. An analysis
      of the meetings by the editorial team will lead to changes intended to improve
      the editorial process in our journal.

PMID- 9609049
TI  - [Comparison of extra renal potassium management in hypertensive, diabetic and
      normal subjects].
AB  - BACKGROUND: Sodium and potassium ions are involved in the regulation of blood
      pressure and the genesis of hypertension. AIM: To assess internal potassium
      balance, as a measure of sodium pump activity, in subjects with essential
      hypertension and diabetic patients. PATIENTS AND METHODS: Eleven hypertensive
      subjects, 5 non-insulin-dependent diabetics and 16 age matched controls were
      studied. An acute oral load of 0.8 mEq/Kg body weight of KCl was administered and
      blood samples were drawn every 30 min thereafter, until 120 min, to measure
      plasma K+ levels. Urinary K+ excretion during this period was also measured. In
      eight hypertensive patients, the test was repeated after two week of
      supplementation with 60 mEq/day of KCl. The maximal increase in plasma potassium
      levels and the time required to achieve the maximum concentration was recorded.
      RESULTS: All patients had normal serum creatinine levels. Mean fasting blood
      glucose of diabetic patients was 133 +/- 15.1 mg/dl. No difference between
      patients and controls in maximal increase plasma potassium increase, was
      observed. In hypertensive patients the lapse to achieve the maximal potassium
      concentration was longer than in controls. After the period of potassium
      supplementation in hypertensive patients, there was a significant increase in
      basal plasma K+ levels and the temporal pattern of plasma potassium increase was
      similar to that of controls. Between 63 and 68% of retained K+ load was
      translocated to the intracellular space at 120 min in all study groups.
      CONCLUSIONS: Internal potassium balance is not significantly altered in subjects
      with essential hypertension or in non-insulin-dependent diabetics.

PMID- 9609050
TI  - [Iodine nutrition in school children of four census areas of Chile].
AB  - BACKGROUND: Although endemic goiter is an easily controlled chronic disease, it
      continues to be a serious global public health problem. AIM: To study iodine
      nutrition in school age children from different areas of Chile. SUBJECTS AND
      METHODS: Thyroid gland was palpated in 4181 school age children from Calama,
      Santiago, Temuco and Punta Arenas. Urinary iodine excretion was measured to 9% of
      these children and iodine concentration in salt for human consumption obtained in
      each of these areas was determined. RESULTS: A 9% goiter prevalence in boys and
      11% prevalence in girls was detected. The prevalence of goiter Ia was 6.5% and
      the figure in different geographic areas was similar. Iodine concentration in
      salt for human consumption was adequate according to Chilean legislation (82.6,
      95.7, 96.8 and 93.2 micrograms ugI/g salt in Calama, Santiago, Temuco and Punta
      Arenas respectively). Urinary iodine excretion in boys and girls was 1695 and
      1802 micrograms l/g creatinine in Calama, 680 and 732 in Santiago, 574 and 690 in
      Temuco, 570 and 528 in Punta Arenas. These values are well above recommendations.
      CONCLUSIONS: Endemic goiter is no longer a problem in Chile. The importance of a
      continuous surveillance of iodine nutrition in Chile and the reduction of salt
      iodine concentration required by Chilean legislation is underscored.

PMID- 9609051
TI  - [Platelet alloimmunization in patients with oncologic blood disorders treated
      with multiple transfusions: prospective study in adults and children].
AB  - BACKGROUND: Refractoriness continues to be a major complication of platelet
      transfusion therapy in patients with multiple transfusions. Despite most cases
      are secondary to non-immune causes, the most serious is that associated to
      alloimmunization. The incidence and consequences of HLA and non-HLA (platelet
      specific) antibodies are unknown in our country. AIM: To prospectively determine
      the frequency and characteristics of post transfusion alloimmunization and the
      incidence of platelet specific antibodies. PATIENTS AND METHODS: Forty one adults
      and 24 children with a recently diagnosed malignancy and undergoing chemotherapy
      that required multiple transfusions were studied. Screening for antiplatelet
      antibodies (platelet membrane ELISA) was performed before the first transfusion,
      every four weeks or whenever the 1 hour corrected count increment for platelet
      transfusions was lower than 5000. Platelet specific antibodies were identified
      with a monoclonal antibody-specific immobilization of platelet antigens (MAIPA),
      with anti-GPIb, GPIIb/IIIa, GPIa/Iia and anti-HLA class I. RESULTS: Adult
      patients received an average of 10.2 +/- 5.5 units of red blood cells and 58.6 +/
      35.4 units of platelets. Children received 4.8 +/- 3.7 units of red blood cells
      and 9.6 +/- 6.7 units of platelets. HLA antibodies appeared in 7 of 41 adult
      patients (17%), platelet specific alloantibodies were found in two patients (one
      anti GP Ia/IIa and one anti GP Ib). Platelet refractoriness appeared in three
      alloimmunized patients. No child had detectable serum antibodies during follow
      up. CONCLUSIONS: Platelet transfusion refractoriness of immune origin occurs
      infrequently in our population and the presence of platelet antibodies does not
      mean that it will appear. The use of leukocyte depleted blood components to
      prevent refractoriness cannot be justified at this time.

PMID- 9609052
TI  - [24 hour esophageal pH monitoring in healthy individuals].
AB  - BACKGROUND: Twenty four hour esophageal pH monitoring is considered the gold
      standard investigation for gastroesophageal reflux disease. This test allows the
      linkage of symptoms to occurrence of reflux episodes and is used to record the
      frequency of reflux and the amount of esophageal acid exposure that results from
      reflux. AIM: To know the acid esophageal exposure in healthy Chilean subjects.
      SUBJECTS AND METHODS: Thirty two asymptomatic volunteers aged 30 to 76 years old
      (24 female) underwent 24 h esophageal pH monitoring with a digitrapper Mark II
      Gold (Synectics Medical Stockholm). Total reflux episodes, episodes greater than
      5 min, the longest reflux episode, the lapse with pH < 5, the percentage of time
      with pH < 4 and the score suggested by Johnson and De Mester were analyzed.
      RESULTS: There was a mean of 20.9 reflux episodes per subject and 0.1 episodes of
      more than 5 min. The longest episode lasted 8 min and the mean total time of acid
      reflux was 10 min/24 h. Total percentage pH below 4 was 0.7% and the mean score
      was 3.2. No subject reported symptoms during the test. CONCLUSIONS: For practical
      purposes, the upper limit of normal acid exposure in Chilean subjects is 2.4%.

PMID- 9609054
TI  - [Lipoprotein lipase gene polymorphism in non-insulin-dependent diabetics:
      preliminary study].
AB  - BACKGROUND: Lipoprotein lipase plays a crucial role in plasma lipoprotein
      metabolism. Several lipoprotein lipase gene polymorphisms have been found
      associated with lipid levels, premature atherosclerosis and cardiovascular
      disease. AIM: To investigate, in the Chilean population, the genotype
      distribution of lipoprotein lipase polymorphisms and its possible association
      with lipid levels and obesity. PATIENTS AND METHODS: Hind III and Pvu II
      polymorphism was determined in 45 non-insulin-dependent diabetic patients and in
      52 non diabetic controls from Santiago, Chile. RESULTS: Hind III (+/+)
      polymorphism had a higher frequency in diabetics as compared to controls (0.6 and
      0.29 respectively, p = 0.009). The frequency of heterozygous distribution was
      higher in non diabetic subjects. Controls and diabetics had comparable gene
      frequencies for the Pvu II genotype distribution. Analyzing the impact of these
      polymorphisms on plasma lipid levels, Hind III (+/+) genotype was associated with
      high levels of total cholesterol and triglycerides in both groups. The
      heterozygote (+/-) or homozygote (-/-) state for Hind III was effectively
      associated with high levels of HDL cholesterol levels, as compared to the (+/+)
      genotype. There was no relationship between these genotypes and body mass index
      and waist to hip ratio. CONCLUSIONS: An association between genetic variation at
      the lipoprotein lipase locus with high levels of triglycerides and total
      cholesterol was confirmed. However, no association of these genetic markers with
      anthropometric measurements was found.

PMID- 9609053
TI  - [Diabetic neuropathy: thermal sensation and metabolic control in non-insulin
      dependent diabetics].
AB  - BACKGROUND: The early detection of peripheral neuropathy in diabetics is
      important since it is the main risk factor for lower limb trophic lesions in
      diabetics. AIM: To assess the relationship between feet thermal sensation
      threshold and metabolic control in ambulatory non-insulin-dependent diabetics.
      PATIENTS AND METHODS: A random sample of 34 non-insulin-dependent diabetics
      followed for more than five years in a special clinic, out of 368 patients, was
      selected. Warmth sensation thresholds were measured in the dorsum of both feet
      using a MSTP-III thermostimulator. The average value of all glycosylated
      hemoglobins obtained during the 9.7 +/- 5.3 years of follow up for each patient
      was calculated. A multiple stepwise regression analysis was performed between
      thermal sensation as the dependent variable and glycosylated hemoglobin, fasting
      blood glucose, age and diabetes duration. RESULTS: The regression model disclosed
      glycosylated hemoglobin as the only independent predictor of warmth sensation
      threshold (partial r = 0.385; p = 0.043). Fifteen diabetic patients with good
      metabolic control, defined as those with a mean glycosylated hemoglobin of less
      than 9.5%, had a warmth sensation threshold of 35.6 +/- 3.7 degrees C, whereas 19
      diabetics with a had control (glycosylated hemoglobin > or = 9.5%) had a
      threshold of 39 +/- 3.8 degrees C (p = 0.017). CONCLUSIONS: In this group of
      diabetics, there is a relationship between the severity of distal polyneuropathy
      and the metabolic control, assessed with glycosylated hemoglobin levels.

PMID- 9609055
TI  - [Comparative analysis of body composition assessment methods in healthy adult
      men].
AB  - BACKGROUND: The degree of agreement between different methods to assess total
      body composition is not well known. AIM: To determine the level of agreement for
      total body fat mass measurement by dual-photon absorptiometry (DEXA),
      bioelectrical impedance (BIA) and anthropometry using the deuterium dilution
      method as the gold-standard technique, in normal male volunteers. SUBJECTS AND
      METHODS: Total body fat mass was measured by DEXA, BIA, anthropometry and
      deuterium dilution in thirty one healthy men, aged 41.9 +/- 8.6 years old.
      RESULTS: Mean differences in percentage of total body fat compared with deuterium
      dilution were 0.3% +/- 2.2, 1.3% +/- 3.4 and 1.8 +/- 2.3% for DEXA1 BIA and
      anthropometry respectively. DEXA had the lower difference with deuterium dilution
      and the confidence intervals for this difference (+/- DS) showed that, at the
      individual level, the maximum difference was 4.4%. CONCLUSIONS: All the methods
      evaluated gave similar average measurements for total body fat mass, but with
      different individual variability. In this group of healthy male subjects, DEXA
      was the best method in terms of agreement with the gold-standard.

PMID- 9609056
TI  - [Endoscopic manometry of Oddi's sphincter].
AB  - BACKGROUND: Endoscopic manometry is the gold standard for the diagnosis of
      sphincter of Oddi dysfunction. AIM: To report the results of the first 30
      endoscopic manometries of sphincter of Oddi performed in a Gastroenterology
      Service. PATIENTS AND METHODS: Thirty manometries were performed in 28 patients
      aged 30 to 70 years old (14 females). The papilla was cannulated with a perfused
      catheter, measuring pressure with external transducers. RESULTS: Deep cannulation
      of the papilla was achieved in 88%. Procedure-related complications were not
      observed in these cases. Normal values were registered in 11 cases with a basal
      sphincter pressure 15.6 +/- 10.7 mm Hg, contractions with an amplitude of 92.3 +/
      35.7 mm Hg and 6.0 +/- 2.4/min frequency. The clinical suspicion of hypertonic
      dyskinesis was confirmed in 5 cases with an elevated basal pressure of 43.69 +/-
      13.3 mm Hg, an increased frequency of contractions ("tachyoddia") in one, and
      large spastic contractions of high pressure in other case. In 3 of 5 cases with
      common bile duct stones, a predominance of retrograde propagation of the
      contractions was observed with normal pressure. Variable manometric results were
      observed after endoscopic papillotomy observing a scale from the complete absence
      of motor activity to normal sphincter function. CONCLUSIONS: Endoscopic manometry
      is a reasonably safe method, of great importance in the diagnosis of functional
      disorders of the sphincter of Oddi.

PMID- 9609057
TI  - [Relevance of the thyroid function assessment in psychiatric patients].
AB  - BACKGROUND: Thyroid dysfunction is frequent in psychiatric outpatients and the
      correction of their endocrine abnormalities seems to improve the response to
      psychopharmacologic treatment. AIM: To retrospectively explore the frequency of
      thyroid abnormalities in psychiatric outpatients. MATERIAL AND METHODS: Clinical
      charts and thyroid assessment of 102 psychiatric patients aged 40.8 +/- 15 years
      old (28 male) seen between April 1995 and September 1996 were reviewed. Endocrine
      diagnosis was made according to international criteria and psychiatric diagnosis
      was made by a single psychiatrist following DSM IV criteria. RESULTS: Forty
      patients (39.2%) had thyroid abnormalities. Thirteen (12.7%) had a diagnosis of
      thyroid problems and were in treatment before they came to the psychiatric
      clinic. Sixteen patients had hypothyroidism (40%), seven had subclinical
      hypothyroidism (17.5%), 12 were euthyroid but had goiter or positive thyroid
      antibodies (30%) and 5 individuals had hyperthyroidism (12.5%). The most frequent
      thyroid abnormality was the presence of positive thyroid antibodies in 16 cases
      (15.7%). No specific association was found between psychiatric and endocrine
      diagnoses. CONCLUSIONS: The design of this study prevents to draw conclusions
      about prevalence of thyroid alterations in psychiatric patients. Nevertheless
      results support the need for routine thyroid assessment in this specific
      population.

PMID- 9609058
TI  - [Hepatitis C virus infection presenting as a polyarthritis: report of 2 cases].
AB  - Several disease have been associated with hepatitis C virus infections, including
      rheumatologic, hematologic and neoplastic disorders. We report two women, aged 57
      and 39 years old whom the initial presentation of hepatitis C virus infection was
      an arthritis resembling rheumatoid arthritis. Laboratory work up revealed
      abnormal liver function tests, stimulating the search for hepatitis C virus
      infection, having both patients positive ELISA tests. Detection of this agent is
      extremely important when selecting a therapy for the articular disease, since
      several drugs used in the treatment of rheumatic disorders are potentially
      hepatotoxic and immunosuppression is risky in the setting of a viral hepatitis.

PMID- 9609059
TI  - [Hypertension treatable with glucocorticoids: report of a case].
AB  - Lately, a series of hypertensive syndromes of unknown etiology that respond to
      new forms of therapy, have been described. One of these is glucocorticoid
      remediable hypertension, that evolves with suppressed plasma renin activity and
      normal or high serum aldosterone levels, that lead to an aldosterone/plasma renin
      activity ratio over 30. We report a 45 years old woman with a severe
      hypertension, despite the use of antihypertensive medications. She had a plasma
      renin activity of less than 0.3 ng/ml/h, normal serum aldosterone levels (10
      ng/ml) and thus a high aldosterone/plasma renin activity ratio. She had normal
      serum potassium and sodium levels. Due to the bad results of conventional
      antihypertensive medications, a treatment with dexamethasone was started, that
      normalized blood pressure and allowed to discontinue other antihypertensive
      medications. This type of hypertension must be sought since non conventional
      treatments could be used for refractory hypertensive syndromes.

PMID- 9609060
TI  - [Renovascular hypertension and abdominal bruit in a case: has its interpretation
      modified technology?].
AB  - A lateral abdominal bruit is considered an important finding for the detection of
      renovascular hypertension. However, the precision and accuracy of new techniques
      such as angiography, Doppler ultrasound and studies with radioisotopes have
      changed its value and clinical interpretation. We report a 75 years old woman
      with a bilateral renal artery stenosis in whom a bruit was heard over the artery
      that did not contribute to the genesis of hypertension and the significant
      arterial stenosis causing hypertension was silent. This particular situation
      could lead to erroneous clinical decisions.

PMID- 9609062
TI  - [Liver transplantation: preoperative assessment].
AB  - Candidates for hepatic transplant require a careful identification of risk
      factors present in the preoperative period. Child C patients have a higher
      incidence of renal function derangement, septic complications and mortality than
      Child A or B patients. Alterations in cardiovascular, renal, respiratory and
      neurologic systems, that sometimes constitute clearly defined syndromes, have
      important prognostic implications. These alterations shed doubts on the moment
      and indications for transplantation and on the correct preoperative management of
      these patients.

PMID- 9609061
TI  - [Thyroid neoplasm of mid follicular-medullary type; an uncommon, particular and
      aggressive form: report of 3 cases].
AB  - Mixed medullary and follicular carcinoma of the thyroid shares secretory and
      immunohistochemical features of both follicular and parafollicular thyroidal
      cells. We report three women, aged 34, 63 and 61 old with this type of tumor. Its
      diagnosis must be bore in mind in patients with thyroidal tumors and a
      histological appearance of a medullary or undifferentiated carcinoma. An early
      diagnosis of a mixed medullary and follicular carcinoma of the thyroid is
      important, considering its special treatment and negative prognosis.

PMID- 9609063
TI  - [Medical treatment of prolactin and growth hormone-secreting pituitary tumors].
AB  - Advances in medical treatment of prolactinomas and acromegaly in the last 20
      years are analyzed. Dopaminergic drugs as bromocriptine, lisuride, pergolide and
      terguride successfully control hyperprolactinemia, reduce tumor size and cause
      clinical improvement. New long lasting medications with less adverse effects such
      as cabergoline, with oral weekly administration, and the repeatable monthly
      injectable form of bromocriptine (Parlodel LAR, Sandoz) may be the treatment of
      choice for prolactinomas. Dopaminergic medications are less effective in
      acromegaly. The higher doses required induce more collateral effects. An
      important step has been the incorporation of long lasting somatostatin analogues
      such as octreotide (for sbc use tid) intramuscular every 28 days injectable
      Sandostatin LAR and lanreotide SR (Somatuline, Ipsen Biotech), injectable every
      10 to 14 days. Medical treatment of acromegaly is not, at the present, an
      alternative to surgery. However, the development of long lasting specific drugs
      may become, in the future, the choice or an alternative in the treatment of
      acromegaly.

PMID- 9609064
TI  - [Medical certification of deaths by trauma in the Chilean health services].
AB  - BACKGROUND: Trauma in the third cause of death in Chile and the most important
      among youngsters. AIM: To analyze the certification of deaths by trauma, studying
      those deaths in which it is not known if they were accidental or self inflicted.
      MATERIAL AND METHODS: Deaths certified as caused by trauma, poisoning or violence
      during the period 1992-1994 are analyzed. Those in which their accidental or self
      inflicted nature was ignored were specially considered. RESULTS: During the study
      period, 26,886 f 225,796 deaths were certified as caused by trauma, poisoning or
      violence. In 41.7% of these deaths, no defined cause (accidental or self
      inflicted) was reported) was reported. In the Metropolitan region 65.3% of deaths
      by trauma were not defined. Ninety seven percent of certificates in this area
      were extended by pathologists or coroners. In all health services, there was a
      positive correlation between the percentage of ill defined deaths by trauma and
      the percentage of certifications by pathologists or coroners. CONCLUSIONS: The
      deficiency in certification of deaths by trauma is possibly due to administrative
      causes and precludes the study of deaths caused by accidents, violence or suicide
      in Chile and its comparison with other countries. An effort should be done to
      solve this problem.

PMID- 9609065
TI  - [Complementary health care models: a neglected component in the health care
      systems reform].
AB  - Complementary health care models represent a neglected and scarcely studied area
      of the health services structure. Within them a myriad of medical therapies of
      various origins are included. Lately, their importance has grown by means of the
      increase in demand for such services, both in industrialized and developing
      countries. It is urgent to reinforce research in the area aiming at understanding
      the processes through which the population demands these services and the
      processes through which complementary practitioners are able to maintain their
      presence in a market environment where the forces of supply and demand are
      significant. The context created by the health services reform should be used to
      review the therapeutic value of these models, to promote its regulation, and to
      amplify the availability of therapeutic options for the population.

PMID- 9609066
TI  - [Time trends in risk factors for chronic diseases: is a new epidemic coming?].

PMID- 9609067
TI  - [Role of nitric oxide in gastrointestinal physiology and in the pathogenesis of
      digestive diseases].

PMID- 9609068
TI  - Dealing with publication bias.

PMID- 9609069
TI  - Health economics: the illusion and the "bladder effect".

PMID- 9609070
TI  - Results of local excision in rectal cancer. Is there good evidence?

PMID- 9609071
TI  - Roll-over test in primigravidae attending a public primary care service.
AB  - OBJECTIVE: To determine the roll-over test (ROT) performance in predicting
      pregnancy-induced hypertension (PIH) in primigravidae aged 15-29 years in a
      public primary care service. METHOD: Prospective cohort study enrolling 369
      consecutive and initially normotensive primigravidae. The ROT was applied within
      28-32 weeks of pregnancy. PIH was defined as diastolic blood pressure (DBP) 90 mm
      Hg or systolic blood pressure (SBP) 140 mm Hg, or a rise in DBP 15 mm Hg or a
      rise in SBP 30 mm Hg. The ROT prognostic properties were calculated, and a
      receiver operating characteristic (ROC) curve was constructed. RESULTS: For the
      20 mm Hg cutoff point, sensitivity was 20% and specificity was 93%. Positive and
      negative predictive values were, respectively, 23% and 92%, for a PIH cumulative
      incidence of 9.5%. With other cutoff points, the ROC curve showed a poor
      discriminatory value of the test. CONCLUSION: The ROT was not useful for
      predicting PIH in a primary prenatal care setting.

PMID- 9609072
TI  - Myelodysplastic syndromes (MDS): prognostic factors and scoring systems.
AB  - OBJECTIVE: To evaluate the score systems of Cassano and Sanz and suggest a new
      one. DESIGN: Case series. LOCATION: Teaching hospitals: EPM UNIFESP and Faculdade
      de Medicina de Botucatu. PARTICIPANTS: 59 patients diagnosed from 1979 to 1992.
      INTERVENTION: Evaluation of clinical-laboratorial data. MEASUREMENT: Statistical
      comparison, uni and multivariate analysis and actuarial survival curves. RESULTS:
      Cassano's system divided the patients into high and low risk (p = 0.0966) while
      Sanz's gave high, intermediate and low risk (p = 0.0108). The univariate analysis
      showed hemoglobin, WBC count, E/M ratio, liver size and blast percentage in BM as
      statistically significant. The multivariate analysis showed blast percentage in
      BM (p = 0.004) and Hb (p = 0.050) as significant. Our system, considering the
      multivariate analysis data, divided the patients into high, intermediate and low
      risk (p = 0.0038). CONCLUSIONS: Sanz's system was more functional than Cassano's,
      while ours showed predictive survival value and ease of use in clinical practice.

PMID- 9609073
TI  - Evaluation of staging, cytoreduction and second-look operation of 119 ovarian
      cancer patients.
AB  - OBJECTIVE: This study was conducted on patients with ovarian cancer in order to
      evaluate survival. DESIGN: A retrospective study of 119 cases of ovarian cancer
      from January 1977 to December 1992 with observation until 1993. LOCATION:
      Department of Gynecology and Obstetrics, Ribeirao Preto School of Medicine, Sao
      Paulo University. PARTICIPANTS: Of the 119 cases, 70 (58.8%) presented epithelial
      carcinomas and 21 (17.6%) tumors of the sexual girdle/stroma. DATA SOURCE: The
      data were obtained from the medical records of the patients. MEASUREMENT:
      Statistical analysis of survival time was based on the nonparametric Mann-Whitney
      test with the level of significance set at P < 0.05. RESULTS: The patients with a
      negative second look had a mean survival of 79.4 +/- 48.5 months versus 24.2 +/-
      15.1 months for patients with a positive second look (P < 0.02). CONCLUSIONS: It
      is concluded that patients with a negative second look present a better prognosis
      compared to those with residual disease.

PMID- 9609074
TI  - Hemophagocytic syndrome: pitfalls in its diagnosis.
AB  - The hemophagocytic syndrome (HS) is characterized by a clinical picture of fever,
      hepatosplenomegaly, lymphadenopathy and peripheral pancytopenia. The morphologic
      hallmark of this syndrome is the phagocytosis of hematopoietic elements by
      morphologically normal macrophages. HS is considered rare and may be a primary
      disease or associated to viral, infection, neoplasias or autoimmune diseases.
      Treatment is controversial and its evolution is often fatal. Anatomo-pathological
      evaluation shows the phenomenon of hemophagocytosis in several organs, especially
      the hematopoietic tissues. We describe a case of HS, discuss its possible causes,
      its clinical and pathologic features, its pathophysiology and therapeutic
      possibilities.

PMID- 9609075
TI  - Saphenous nerve entrapment manifested as proximal cruralgia.
AB  - A 16 year old boy had continuous pain in the right testis, groin, and the medial
      aspect of the thigh and knee for 16 months. The onset of symptoms was acute and
      pain distribution included a retrograde area in relation to the entrapment site.
      Tinel's sign was the clue for diagnosis. Diagnosis was confirmed at operation and
      division of the aponeurosis of Hunter's canal relieved the symptoms for three
      days. A second surgical exploration, proximal to the former one, was performed
      after five months. The right femoral nerve was found normal. This new operation
      was therapeutically ineffective. Causes of pain distribution and relapsed pain
      are discussed. The relapse was attributed to myofascial pain syndrome. This
      diagnosis should be considered independently of the correct treatment of the
      primary lesion.

PMID- 9609076
TI  - Muscle pathology in juvenile dermatomyositis.
AB  - OBJECTIVE: To study muscle biopsies, using histochemistry, on ten children with
      infantile dermatomyositis. DESIGN: Series of ten patients (of whom eight patients
      had received treatment and two had not) were submitted to muscle biopsy in order
      to diagnose possible inflammatory myopathy or to detect recurrences. PLACE OF
      DEVELOPMENT OF THE STUDY: Public Health Service of Sao Paulo State. PARTICIPANTS:
      Children with clinical features of inflammatory myopathy. INTERVENTION: Biopsies
      were performed on the vastus lateralis using local anesthetic. Histochemistry was
      performed according to standardized methods. RESULTS: Architectural changes of
      the muscle fibers, necrosis of variable intensity and accentuated evidence of
      regeneration were observed in patients who had not received treatment (2 cases)
      and in one case where muscular weakness persisted in spite of corticosteroid
      therapy. Necrosis and regeneration were minimal or absent in cases treated for
      one year or more (4 cases). In 3 cases with clinical and laboratorial
      recurrences, muscle necrosis and architectural changes were detected.
      CONCLUSIONS: It was concluded that muscle biopsy could aid in diagnosing
      infantile dermatomyositis as well as in detecting recurrences even in cases
      without clinical activity of the disease.

PMID- 9609077
TI  - Legislation of human cloning in the United States.

PMID- 9609078
TI  - Signaling hypertrophy: how many switches, how many wires.

PMID- 9609079
TI  - Clinical and epidemiological significance of left ventricular mass assessed in
      children and adolescents.

PMID- 9609080
TI  - Managed care and patients with cardiovascular disease.

PMID- 9609081
TI  - Real-time three-dimensional echocardiography for determining right ventricular
      stroke volume in an animal model of chronic right ventricular volume overload.
AB  - BACKGROUND: The lack of a suitable noninvasive method for assessing right
      ventricular (RV) volume and function has been a major deficiency of two
      dimensional (2D) echocardiography. The aim of our animal study was to test a new
      real-time three-dimensional (3D) echo imaging system for evaluating RV stroke
      volumes. METHODS AND RESULTS: Three to 6 months before hemodynamic and 3D
      ultrasonic study, the pulmonary valve was excised from 6 sheep (31 to 59 kg) to
      induce RV volume overload. At the subsequent session, a total of 14 different
      steady-state hemodynamic conditions were studied. Electromagnetic (EM) flow
      probes were used for obtaining aortic and pulmonic flows. A unique phased-array
      volumetric 3D imaging system developed at the Duke University Center for Emerging
      Cardiovascular Technology was used for ultrasonic imaging. Real-time volumetric
      images of the RV were digitally stored, and RV stroke volumes were determined by
      use of parallel slices of the 3D RV data set and subtraction of end-systolic
      cavity volumes from end-diastolic cavity volumes. Multiple regression analyses
      showed a good correlation and agreement between the EM-obtained RV stroke volumes
      (range, 16 to 42 mL/beat) and those obtained by the new real-time 3D method
      (r=0.80; mean difference, -2.7+/-6.4 mL/beat). CONCLUSIONS: The real-time 3D
      system provided good estimation of strictly quantified reference RV stroke
      volumes, suggesting an important application of this new 3D method.

PMID- 9609082
TI  - Tracking of left ventricular mass in children: race and sex comparisons: the MCV
      Twin Study. Medical College of Virginia.
AB  - BACKGROUND: Increased left ventricular (LV) mass is a predictor of cardiovascular
      disease in adults. The mechanism(s) for these observations are not fully
      understood. METHODS AND RESULTS: We repeatedly studied a biracial sample of
      children from ages 11 through 17 years. At visits 1 through 5, height, weight,
      and pubertal stage were determined. Blood pressure and heart rate were measured.
      M-mode and two-dimensional echocardiograms were performed with a 3.5-MHz
      transducer with the subject in the supine position. LV mass was calculated.
      Repeated-measures analysis using a mixed modeling approach was performed for LV
      mass. At all ages, boys had greater LV mass than girls. For the population as a
      whole, we found significant tracking correlations for LV mass between each
      interval of measurement and throughout the entire period of examination. The
      tracking correlation for the entire sample from visit 1 through visit 5 was
      r=.41. The LV mass in white children tracked from the youngest to the oldest.
      Black children tracked similarly from ages 1 to 15 years, but tracking was not
      significant across the widest interval, visit 1 through visit 5. Racial
      differences were found in the interactions of systolic blood pressure and heart
      rate, which magnified the differences in LV mass. During adolescence, LV mass
      tracks significantly in both black and white children. CONCLUSIONS: Interactive
      effects such as weight, blood pressure, and heart rate magnify sex and race
      differences in LV mass.

PMID- 9609083
TI  - Left ventricular geometry and severe left ventricular hypertrophy in children and
      adolescents with essential hypertension.
AB  - BACKGROUND: Left ventricular (LV) hypertrophy has been established as an
      independent risk factor for cardiovascular disease in adults. Recent research has
      refined this relationship by determining a cutpoint of 51 g/m(2.7) for LV mass
      index indicative of increased risk and defining LV geometric patterns that are
      associated with increased risk. The purpose of this study was to evaluate severe
      LV hypertrophy and LV geometry in children and adolescents with essential
      hypertension. METHODS AND RESULTS: A cross-sectional study of young patients
      (n=130) with persistent blood pressure elevation above the 90th percentile was
      conducted. Nineteen patients (14%) had LV mass greater than the 99th percentile;
      11 of these were also above the adult cutpoint of 51 g/m(2.7). Males, subjects
      with greater body mass index, and those who had lower heart rate at maximum
      exercise were at significantly (P<.05) higher risk of severe LV hypertrophy. In
      addition, 22 patients (17%) had concentric LV hypertrophy, a geometric pattern
      that is associated with increased risk of cardiovascular disease in adults. Seven
      patients had LV mass index above the cutpoint and concentric hypertrophy. No
      consistent significant determinants of LV geometry were identified in these
      children and adolescents with hypertension. CONCLUSIONS: Severe LV hypertrophy
      and abnormal LV geometry are relatively prevalent in young patients with
      essential hypertension. These findings suggest that these patients may be at risk
      for future cardiovascular disease and underscore the importance of recognition
      and treatment of blood pressure elevation in children and adolescents. Weight
      loss is an important component of therapy in young patients with essential
      hypertension who are overweight.

PMID- 9609084
TI  - Diabetes mellitus, glycoprotein IIb/IIIa blockade, and heparin: evidence for a
      complex interaction in a multicenter trial. EPILOG Investigators.
AB  - BACKGROUND: After angioplasty, major complications and ischemic events occur more
      frequently in diabetic than nondiabetic patients. To determine whether treatment
      with abciximab is effective in reducing these events in diabetics, we analyzed
      characteristics and outcomes of diabetic patients enrolled in a large multicenter
      study (EPILOG). METHODS AND RESULTS: Of 2792 patients enrolled, 638 (23%) were
      diabetic. Diabetic patients were older, shorter, and heavier; more likely to be
      female and have three-vessel disease, prior coronary artery bypass graft surgery,
      a history of hypertension, or a recent myocardial infarction; and less likely to
      be current smokers than their nondiabetic counterparts. During hospitalization,
      death, myocardial infarction, or urgent revascularization occurred in 7.1% of
      diabetics and 7.5% of nondiabetics. By 6 months, the composite of death and
      myocardial infarction had occurred in 8.8% of diabetic patients and 7.4% of
      nondiabetics, whereas death, myocardial infarction, or revascularization had
      occurred in 27.2% and 22.6%, respectively. Abciximab treatment reduced death or
      myocardial infarction among diabetic and nondiabetic patients (hazard ratios,
      0.28 [95% confidence interval (CI), 0.13 to 0.57] and 0.47 [95% CI, 0.33 to 0.70]
      at 30 days for diabetics and nondiabetics, respectively, and 0.36 [95% CI, 0.21
      to 0.61] and 0.60 [95% CI, 0.44 to 0.82] at 6 months for diabetics and
      nondiabetics, respectively). Abciximab reduced target vessel revascularization
      among nondiabetic patients (hazard ratio, 0.78 [95% CI, 0.63 to 0.96]) but not
      among diabetics (hazard ratio, 1.4 [95% CI, 0.94 to 2.08]). When standard- and
      low-dose heparin adjuncts were compared, diabetics receiving abciximab with
      standard-dose heparin had marginally greater reductions in the composite of death
      and myocardial infarction and in target vessel revascularization than diabetics
      assigned to abciximab with low-dose heparin. CONCLUSIONS: Abciximab treatment in
      diabetic patients led to a reduction in the composite of death and myocardial
      infarction, which was at least as great as that seen in nondiabetic patients.
      However, target vessel revascularization was reduced in nondiabetic but not
      diabetic patients. This effect may be associated in part with lower doses of
      heparin. These differences may be related to differences in the platelet and
      coagulation systems between diabetics and nondiabetics, the greater extent of
      coronary artery disease in diabetics, or patient selection and management
      factors.

PMID- 9609085
TI  - Plasma N-terminal pro-brain natriuretic peptide and adrenomedullin: new
      neurohormonal predictors of left ventricular function and prognosis after
      myocardial infarction.
AB  - BACKGROUND: Newly discovered circulating peptides, N-terminal pro-brain
      natriuretic peptide (N-BNP) and adrenomedullin (ADM), were examined for
      prediction of cardiac function and prognosis and compared with previously
      reported markers in 121 patients with myocardial infarction. METHODS AND RESULTS:
      The association between radionuclide left ventricular ejection fraction (LVEF)
      and N-BNP at 2 to 4 days (r=-.63, P<.0001) and 3 to 5 months (r=-.58, P<.0001)
      after infarction was comparable to that for C-terminal BNP and far stronger than
      for ADM (r=-.26, P<.01), N-terminal atrial natriuretic peptide (N-ANP), C
      terminal ANP, cGMP, or plasma catecholamine concentrations. For prediction of
      death over 24 months of follow-up, an early postinfarction N-BNP level > or = 160
      pmol/L had sensitivity, specificity, positive predictive value, and negative
      predictive values of 91%, 72%, 39%, and 97%, respectively, and was superior to
      any other neurohormone measured and to LVEF. Only 1 of 21 deaths occurred in a
      patient with an N-BNP level below the group median (Kaplan-Meier survival
      analysis, P<.00001). For prediction of heart failure (left ventricular failure),
      plasma N-BNP > or = 145 pmol/L had sensitivity (85%) and negative predictive
      value (91%) comparable to the other cardiac peptides and was superior to ADM,
      plasma catecholamines, and LVEF. By multivariate analysis, N-BNP but not ADM
      provided predictive information for death and left ventricular failure
      independent of patient age, sex, LVEF, levels of other hormones, and previous
      history of heart failure, myocardial infarction, hypertension, or diabetes.
      CONCLUSIONS: Plasma N-BNP measured 2 to 4 days after myocardial infarction
      independently predicted left ventricular function and 2-year survival.
      Stratification of patients into low- and high-risk groups can be facilitated by
      plasma N-BNP or BNP measurements, and one of these could reasonably be included
      in the routine clinical workup of patients after myocardial infarction.

PMID- 9609086
TI  - Glutathione-related antioxidant defenses in human atherosclerotic plaques.
AB  - BACKGROUND: Oxidative stress, resulting from an antioxidant/prooxidant imbalance,
      seems to be crucial in atherogenesis. Recent evidence has emerged, however, of a
      surprisingly high content of low-molecular-weight antioxidants in human
      atherosclerotic plaques, although other antioxidant systems have not been
      investigated in these lesions. METHODS AND RESULTS: We studied glutathione
      related antioxidant defenses (which play a key role in tissue antioxidant
      protection) in carotid atherosclerotic plaques of 13 patients subjected to
      endarterectomy and in normal internal mammary arteries of 13 patients undergoing
      coronary artery bypass surgery. Selenium-dependent glutathione peroxidase
      activity was undetectable in the plaques of 7 patients; the other 6 patients with
      plaques showed a mean enzymatic activity approximately 3.5-fold lower than that
      of mammary arteries. Glutathione reductase activity was also markedly lower in
      the plaques than in the arteries. Glutathione transferase instead had comparable
      activity in the two tissues. Remarkably, 5 of the 7 patients with an undetectable
      selenium-dependent glutathione peroxidase activity but none of the 6 with a
      detectable one were characterized by multivascular atherosclerotic involvement (3
      patients) or stenosis of the contralateral carotid artery (2 patients).
      CONCLUSIONS: A weak glutathione-related enzymatic antioxidant shield is present
      in human atherosclerotic lesions. Although the cause of this phenomenon remains
      to be determined, the present data suggest that a specific antioxidant/prooxidant
      imbalance operative in the vascular wall may be involved in atherogenic processes
      in humans.

PMID- 9609087
TI  - Electropharmacologic effects of class I and class III antiarrhythmia drugs on
      typical atrial flutter: insights into the mechanism of termination.
AB  - BACKGROUND: Acute effects of class I and class III antiarrhythmia drugs on the
      reentrant circuit of typical atrial flutter are not fully studied. Furthermore,
      the critical electrophysiologic determinants of flutter termination by
      antiarrhythmia drugs are not clear. METHODS AND RESULTS: The study population
      consisted of 36 patients (mean age, 53+/-17 years) with clinically documented
      typical atrial flutter. A 20-pole "halo" catheter was positioned around the
      tricuspid annulus. Incremental pacing was performed to measure the conduction
      velocity along the isthmus and lateral wall, and extrastimulation was performed
      to evaluate atrial refractory period in the baseline state and after intravenous
      infusion of ibutilide, propafenone, and amiodarone. Efficacy of these drugs in
      conversion of typical atrial flutter and patterns of termination were also
      determined. Ibutilide significantly increased the atrial refractory period and
      decreased conduction velocity in the isthmus at short pacing cycle length. It
      terminated atrial flutter in 8 (67%) of 12 patients after prolongation of flutter
      cycle length due to increase (86+/-19%) of conduction time in the isthmus.
      Propafenone predominantly decreased conduction velocity with use dependency and
      significantly increased atrial refractory period, but it only converted atrial
      flutter in 4 (33%) of 12 patients. Amiodarone had fewer effects on atrial
      refractory period and conduction velocity than did ibutilide and propafenone, and
      it terminated atrial flutter in only 4 (33%) of 12 patients. Termination of
      typical atrial flutter was due to failure of wave front propagation through the
      isthmus, which occurred with cycle length oscillation, abruptly without
      variability of cycle length, or after premature activation of the reentrant
      circuit. CONCLUSIONS: Ibutilide, with a unique increase in atrial refractoriness,
      was more effective in conversion of atrial flutter than were propafenone and
      amiodarone.

PMID- 9609088
TI  - Patent foramen ovale is an important predictor of adverse outcome in patients
      with major pulmonary embolism.
AB  - BACKGROUND: Right-to-left shunt through a patent foramen ovale is frequently
      diagnosed by contrast echocardiography and can be particularly prominent in the
      presence of elevated pressures in the right side of the heart. Its prognostic
      significance in patients with pulmonary thromboembolism, however, is unknown.
      METHODS AND RESULTS: The present prospective study included 139 consecutive
      patients with major pulmonary embolism diagnosed on the basis of clinical,
      echocardiographic, and cardiac catheterization criteria. All patients underwent
      contrast echocardiography at presentation. The end points of the study were
      overall mortality and complicated clinical course during the hospital stay
      defined as death, cerebral or peripheral arterial thromboembolism, major
      bleeding, or need for endotracheal intubation or cardiopulmonary resuscitation.
      Patent foramen ovale was diagnosed in 48 patients (35%). These patients had a
      death rate of 33% as opposed to 14% in patients with a negative echo-contrast
      examination (P=.015). Logistic regression analysis demonstrated that the only
      independent predictors of mortality in the study population were a patent foramen
      ovale (odds ratio [OR], 11.4; P<.001) and arterial hypotension at presentation
      (OR, 26.3; P<.001). Patients with a patent foramen ovale also had a significantly
      higher incidence of ischemic stroke (13% versus 2.2%; P=.02) and peripheral
      arterial embolism (15 versus 0%; P<.001). Overall, the risk of a complicated in
      hospital course was 5.2 times higher in this patient group (P<.001). CONCLUSIONS:
      In patients with major pulmonary embolism, echocardiographic detection of a
      patent foramen ovale signifies a particularly high risk of death and arterial
      thromboembolic complications.

PMID- 9609089
TI  - Pressure overload induces cardiac hypertrophy in angiotensin II type 1A receptor
      knockout mice.
AB  - BACKGROUND: Many studies have suggested that the renin-angiotensin system plays
      an important role in the development of pressure overload-induced cardiac
      hypertrophy. Moreover, it has been reported that pressure overload-induced
      cardiac hypertrophy is completely prevented by ACE inhibitors in vivo and that
      the stored angiotensin II (Ang II) is released from cardiac myocytes in response
      to mechanical stretch and induces cardiomyocyte hypertrophy through the Ang II
      type 1 receptor (AT1) in vitro. These results suggest that the AT1-mediated
      signaling is critical for the development of mechanical stress-induced cardiac
      hypertrophy. METHODS AND RESULTS: To determine whether AT1-mediated signaling is
      indispensable for the development of pressure overload-induced cardiac
      hypertrophy, pressure overload was produced by constricting the abdominal aorta
      of AT1A knockout (KO) mice. Quantitative reverse transcriptase-polymerase chain
      reaction revealed that the cardiac AT1 (probably AT1B) mRNA levels in AT1A KO
      mice were <10% of those of wild-type (WT) mice and were not affected by pressure
      overload. Chronic treatment with subpressor doses of Ang II increased left
      ventricular mass in WT mice but not in KO mice. Pressure overload, however, fully
      induced cardiac hypertrophy in KO as well as WT mice. There were no significant
      differences between WT and KO mice in expression levels of fetal-type cardiac
      genes, in the left ventricular wall thickness and systolic function as revealed
      by the transthoracic echocardiogram, or in the histological changes such as
      myocyte hypertrophy and fibrosis. CONCLUSIONS: AT1-mediated Ang II signaling is
      not essential for the development of pressure overload-induced cardiac
      hypertrophy.

PMID- 9609090
TI  - PDGF-receptor tyrosine kinase blocker AG1295 selectively attenuates smooth muscle
      cell growth in vitro and reduces neointimal formation after balloon angioplasty
      in swine.
AB  - BACKGROUND: Signaling through protein tyrosine kinases (PTKs) is a major
      contributor to the transmission of mitogenic stimuli to the interior of the cell
      and nucleus. The present study was designed to determine the effect of the
      tyrphostin AG1295, a selective blocker of PDGF-receptor PTK, on the growth of
      porcine and human smooth muscle cells (SMCs) in culture, on the outgrowth
      kinetics of SMCs from porcine and human arterial explants, and on neointimal
      formation after balloon injury in pigs. METHODS AND RESULTS: SMCs for culture
      were obtained from porcine abdominal aortas, human internal mammary arteries, and
      endarterectomy tissue from a single human carotid artery. Addition of AG1295 to
      SMCs before PDGF stimulation completely inhibited PDGF-beta-receptor tyrosine
      phosphorylation without affecting the level of PDGF-beta-receptor. AG1295
      resulted in a selective, reversible inhibition of SMC proliferation in culture
      (76%) with only mild (13.5%) inhibition of endothelial cell proliferation. The
      number of SMCs accumulating around explants of porcine carotid arteries and human
      endarterectomy specimens 12, 15, 19, 22, and 24 days after plating was reduced by
      82% to 92% in AG1295-treated compared with nontreated specimens, and initiation
      of SMC outgrowth was markedly delayed. The numbers of cells accumulated 10 days
      after initiation of outgrowth were significantly lower in treated versus control
      explants. Local intravascular delivery of AG1295-impregnated polylactic acid
      based nanoparticles (130+/-25 nm) to the site of balloon injury to porcine
      femoral arteries resulted in significant reductions in intima/media area ratio
      and luminal cross-sectional area narrowing by neointima compared with
      contralateral control arteries to which empty nanoparticles were applied (0.15+/
      0.07 versus 0.09+/-0.03, P=.046 and 20+/-4% versus 10+/-4%, P=.0009, n=6 for
      both). CONCLUSIONS: The tyrphostin AG1295, a selective blocker of PDGF-receptor
      kinase, exerts a marked inhibitory effect on the activation, migration, and
      proliferation of porcine and human SMCs in vitro and an approximately 50%
      inhibitory effect on neointimal formation after balloon injury in porcine femoral
      arteries when delivered via biodegradable nanoparticles. Further studies appear
      to be warranted to evaluate the applicability of this novel approach to the
      interventional setting.

PMID- 9609092
TI  - Cardiac pacing, 1960-1985: a quarter century of medical and industrial
      innovation.

PMID- 9609091
TI  - Doppler tissue imaging quantitates regional wall motion during myocardial
      ischemia and reperfusion.
AB  - BACKGROUND: Quantification of regional myocardial function is a major unresolved
      issue in cardiology. We evaluated the accuracy of pulsed Doppler tissue imaging
      (DTI), a new echocardiographic technique, to quantify regional myocardial
      dysfunction induced by acute ischemia and reperfusion. METHODS AND RESULTS: In
      nine open-chest anesthetized pigs, various degrees of regional wall motion
      abnormalities were induced by graded reduction of left anterior descending
      coronary artery (LAD) blood flow. Pulsed Doppler tissue imaging was performed
      from an epicardial apical four-chamber view with the sample placed within the
      middle part of the septal wall. Peak septal velocities were calculated during
      systole, isovolumic relaxation, and early and late diastole. Regional myocardial
      blood flow and systolic and diastolic dysfunctions were assessed by radioactive
      microspheres and ultrasonic crystals, respectively. Ischemia resulted in a
      significant rapid reduction of systolic velocities and an early decrease in the
      ratio of early to late diastolic velocities. Both changes were detected by pulsed
      DTI within 5 seconds of coronary artery occlusion. The decrease in systolic
      velocity significantly correlated with both systolic shortening (r=.90, P<.0001)
      and regional myocardial blood flow (r=.96, P<.0001) during reduction of LAD blood
      flow. CONCLUSIONS: These results suggest that DTI may be a promising new tool for
      the quantification of ischemia-induced regional myocardial dysfunction.

PMID- 9609093
TI  - Images in cardiovascular medicine. Partial pericardial defect.

PMID- 9609094
TI  - Images in cardiovascular medicine. Malignant cardiac pheochromocytoma with bone
      metastases.

PMID- 9609095
TI  - Twelfth Aspen Cancer Conference: mechanisms of toxicity and carcinogenesis.

PMID- 9609097
TI  - Inhibitory effects of pentoxifylline on ultraviolet B light-induced cutaneous
      inflammation.
AB  - It is now recognized that ultraviolet (UV) radiation is a potent environmental
      insult capable of interfering with immunity to skin cancers and modifying certain
      immunologic reactions within both locally irradiated skin and distant, unexposed
      sites. Exposure to UVB light (290-320 nm) induces a potent cutaneous inflammatory
      response that involves the infiltration of leukocytes into the dermis as well as
      the production of proinflammatory cytokines by both resident epidermal
      keratinocytes and dermal cells. Tumor necrosis factor-alpha (TNF-alpha) is a
      proinflammatory cytokine that has been shown to be a major mediator of UVB light
      effects on cutaneous immunity. Recent studies have demonstrated that
      pentoxifylline (PTX), a xanthine-derived phosphodiesterase inhibitor, has the
      ability to inhibit synthesis of TNF-alpha. To examine the effects of PTX on UVB
      mediated cutaneous inflammation, Skh/hr hairless mice were injected
      intraperitoneally with either phosphate-buffered saline or 50 microg/g PTX 1 h
      before exposure to 2240 J/m2 UVB. Reverse transcription-polymerase chain reaction
      and immunohistochemical techniques were used to demonstrate that 24 h to 1 wk
      after UVB-light irradiation, PTX inhibited UVB-induced TNF-alpha gene expression,
      inhibited the increase in epidermal TNF-alpha protein synthesis, blocked the
      increase in epidermal proliferation observed after exposure to UVB light, and
      decreased production of myeloperoxidase by neutrophils infiltrating into the
      dermis. These studies demonstrated that PTX modifies epidermal responses after
      acute UVB light exposure and suggest that PTX treatment may be used clinically to
      modulate the deleterious effects of long-term UVB-light irradiation.

PMID- 9609096
TI  - Few point mutations in elongation factor-1gamma gene in gastrointestinal
      carcinoma.
AB  - Elongation factor-1 (EF-1) gamma is overexpressed in a high proportion of
      gastrointestinal cancers. The mechanism of overexpression has not been
      determined. The purpose of this study was to examine cDNA specimens from
      pancreatic and colorectal cancer for mutation in this gene, which would allow us
      to determine whether gene mutations are responsible for overexpression of EF
      1gamma. In one colorectal carcinoma, we detected an A-->G transition at amino
      acid codon 158 (T-->C in the sense strand) resulting in a change from a leucine
      to a serine. The base change was not detected in cDNA isolated from normal
      appearing tissue from the same patient. We did not find mutations in another five
      colorectal carcinoma and five pancreatic cancer samples. Thus, although we
      detected a mutation in one tumor, the frequency of mutations was too low to
      account for the high frequency of overexpression of the EF-1gamma RNA in
      colorectal cancer. We also investigated other possible mechanisms of
      overexpression of the EF-1gamma RNA in this study. Slot-blot analysis of DNA
      isolated from colorectal cancers showed that the overexpression was not due to
      gene amplification. Using serum starvation to synchronize cultured cells, we
      showed that the overexpression was also not due to an increase in the number of
      cycling cells, as occurs in cancer. Using Southern blot analysis, we were unable
      to detect genome rearrangements that could have been responsible for the
      overexpression. In conclusion, the mechanism for overexpression of the EF-1gamma
      gene in colorectal and pancreatic cancer remains unknown. However, mutations in
      the coding sequence of the gene, gene amplification, and gene rearrangement do
      not account for the high frequency of overexpression of this gene, and the
      overexpression is not due to an increase in the number of cycling cells.

PMID- 9609098
TI  - Tumor suppressor function of a dominant negative retinoic acid receptor mutant.
AB  - Mutations in receptors for the vitamin A metabolite retinoic acid (RAR) that
      repress retinoic acid (RA)-responsive gene expression have been identified and
      characterized. We previously reported an absence of target gene response to RA in
      all but one of a series of transformed human epithelial cell lines. To elucidate
      the mechanisms of this unresponsiveness, we created stable transfectants that
      expressed an RARalpha mutant (RARalpha403) previously shown to have dominant
      negative activity due to a C-terminal truncation. All clones exhibited repressed
      RA-responsive gene expression. These cells grew slowly and demonstrated greater
      growth inhibition by RA. Pretreatment of both control and experimental groups
      with RA enhanced epidermal growth factor-induced proliferation despite RA
      dependent downregulation of epidermal growth factor receptor expression. In
      addition, clones expressing the mutant RARalpha were 60% less invasive in an in
      vitro assay. This reduced invasiveness correlated with decreased gelatinase
      activity in these cells. We showed for the first time that a dominant negative
      mutation in RARalpha can function as a tumor suppressor in transformed epithelial
      cells.

PMID- 9609099
TI  - Mapping a novel cellular-senescence gene to human chromosome 2q37 by irradiation
      microcell-mediated chromosome transfer.
AB  - To identify the subchromosomal region that carries the cellular-senescence
      restoring program of the human cervical carcinoma cell line SiHa, we constructed
      by irradiation microcell-mediated chromosome transfer a library of mouse A9 cells
      containing various fragments of human chromosome 2 tagged with pSV2neo in 2p11
      p12. Eighty-seven clones were isolated and screened for the presence of human
      sequences by inter-Alu and inter-L1 polymerase chain reaction (PCR), and six
      clones exhibiting PCR-laddering patterns that differed from those of the A9 cells
      containing an intact chromosome 2 were examined further. Chromosome analysis and
      fluorescence in situ hybridization (FISH) using human-specific repetitive
      sequences revealed that four of these clones contained single subchromosomal
      transferable fragments (STFs). Southern blot hybridization of 14 cosmid markers
      revealed that the STFs in A9 cells were derived from human chromosome 2. These
      STFs were transferred into SiHa cells by microcell fusion, and one of the STFs
      restored the cellular-senescence program. The concordance of the cellular
      senescence-restoring program with the presence or absence of specific DNA
      fragments of chromosome 2 indicated that the putative cellular-senescence gene
      was located in 2q32-qter. For more detailed mapping, we constructed mouse A9
      cells containing STFs derived from human chromosome 2 tagged with pSTneo at
      different regions in 2q31-qter. PCR-laddering and FISH analyses were used to
      identify six clones that contained different STFs. These STFs were transferred
      into SiHa cells, and one of the three clones that restored cellular senescence
      contained a small fragment of human chromosome 2. This STF was shown by PCR
      analysis using 14 human chromosome 2-specific primer pairs to be smaller than
      12.2 cM and was mapped to the 2q37 region by FISH analysis with inter-Alu PCR.
      Beta-galactosidase activity, which is a biomarker of senescent cells, and
      telomerase activity similar to that found in parental SiHa cells were detected in
      SiHa microcell hybrids, suggesting that the putative cellular-senescence gene was
      not involved in a telomerase pathway but rather in an alternate pathway of
      cellular senescence.

PMID- 9609100
TI  - Reduction in transforming growth factor-beta type II receptor in mouse lung
      carcinogenesis.
AB  - Transforming growth factor-beta (TGF-beta) is a growth modulator that inhibits
      the proliferation of many epithelial cells through interaction with its
      receptors, the type I and type II receptors (TGF-beta RI and RII) by activating
      their serine/threonine kinase activities. Loss of growth inhibition by TGF-beta
      is thought to contribute to the development of many types of tumors. To examine
      the roles of TGF-beta1, -beta2, and -beta3 and TGF-beta RI and RII in chemically
      induced mouse lung tumorigenesis, we used immunohistochemical and in situ
      hybridization analyses to measure the expression of their proteins and mRNAs in
      A/J mice treated with the carcinogen urethane to induce lung adenomas.
      Immunostaining for the TGF-beta ligands and receptors was detected in the
      epithelia of the bronchioles of untreated and treated A/J mice at similar levels.
      Immunostaining for the TGF-beta ligands and receptors was also detected in
      adenomas by 2 mo. While immunostaining for TGF-beta1, -beta2, and -beta3 and TGF
      beta RI in adenomas was detected at levels comparable to those in bronchioles,
      immunostaining for TGF-beta RII was less intense in adenomas than in bronchioles.
      Decreased immunostaining for TGF-beta RII in adenomas persisted for at least 8 mo
      after exposure to urethane, whereas immunostaining for TGF-beta1, -beta2, and 
      beta3 and TGF-beta RI persisted at levels comparable to those in normal
      bronchioles. In situ hybridization studies conducted with TGF-beta receptor
      riboprobes showed a corresponding reduction in expression of TGF-beta RII mRNA
      but not of TGF-beta RI mRNA in adenomas compared with expression in bronchioles.
      Expression of TGF-beta RII mRNA was also examined in non-tumorigenic and
      tumorigenic mouse lung cells; expression of TGF-beta RII mRNA was lower in the
      tumorigenic cells derived from urethane-induced lung tumors. These data suggest
      that a decrease in expression of TGF-beta RII may contribute to autonomous cell
      growth and may play an important role in mouse lung carcinogenesis induced by
      urethane.

PMID- 9609101
TI  - Inhibitory effect of matrilysin antisense oligonucleotides on human colon cancer
      cell invasion in vitro.
AB  - In colorectal cancer, matrilysin (matrix metalloproteinase-7) is mainly produced
      by the tumor cells themselves and is thought to play an important role in tumor
      invasion and metastasis. In the study reported here, we examined the effects of
      matrilysin antisense phosphorothioate oligonucleotides on both the expression of
      matrilysin and the invasive potential of the human colon cancer cell line CaR-1
      in vitro. To select the most specific and potent oligonucleotide sequence, we
      performed extensive analyses of the binding specificities of all antisense
      candidates in the GenBank database by using a computer program we developed. As a
      result, a 15-mer matrilysin-specific antisense oligonucleotide that hybridizes to
      the coding region of matrilysin mRNA (AS-1) and a random control oligonucleotide
      (CL-1) were designed. Reverse transcription-polymerase chain reaction and western
      blot analysis demonstrated that 10 microM AS-1 suppressed matrilysin expression
      at both the mRNA level (92%) and protein level (64%). In vitro invasion assays
      demonstrated that this same concentration of AS-1 inhibited the ability of cells
      to invade a reconstituted basement membrane by 50% as compared with the ability
      of untreated cells to do so. On the other hand, CL-1, which had the same length
      and GC content as AS-1, did not show any inhibitory effect. These results
      demonstrate that the antisense oligonucleotide AS-1 inhibits matrilysin
      activities in a sequence-specific manner and suggest that AS-1 has the potential
      to be used as an anti-metastatic agent in an in vivo experimental model of colon
      cancer.

PMID- 9609102
TI  - A historical perspective on oxaliplatin: rethinking the role of platinum
      compounds and learning from near misses.

PMID- 9609103
TI  - Oxaliplatin: mechanism of action and antineoplastic activity.
AB  - Oxaliplatin, a platinum-based chemotherapeutic agent with a 1,2
      diaminocyclohexane (DACH) carrier ligand, has shown in vitro and in vivo efficacy
      against many tumor cell lines, including some that are resistant to cisplatin and
      carboplatin. The retention of the bulky DACH ring by activated oxaliplatin is
      thought to result in the formation of platinum-DNA adducts, which appear to be
      more effective at blocking DNA replication and are more cytotoxic than adducts
      formed from cisplatin. Studies by the National Cancer Institute (NCI) have
      suggested that oxaliplatin has a spectrum of activity different from that of
      either cisplatin or carboplatin, suggesting that it has different molecular
      targets and/or mechanisms of resistance. Oxaliplatin has been demonstrated to
      differ in some mechanisms associated with the development of cisplatin
      resistance. Compared with cisplatin-conditioned cells, deficiencies in mismatch
      repair (MMR) and increases in replicative bypass, which appear to contribute to
      cisplatin resistance, have not been shown to induce a similar resistance to
      oxaliplatin. A decreased likelihood of resistance development makes oxaliplatin a
      good candidate for first-line therapy. Studies also demonstrate additive and/or
      synergistic activity with a number of other compounds, however, suggesting the
      possible use of oxaliplatin in combination therapies.

PMID- 9609104
TI  - Pharmacokinetics and safety profile of oxaliplatin.
AB  - In early clinical trials, oxaliplatin has demonstrated significant activity
      against colorectal cancer, both as a single agent and in combination with 5
      fluorouracil (5-FU) and folinic acid (FA). Oxaliplatin differs from cisplatin in
      its lack of nephrotoxicity and from carboplatin in its hematologic toxicity being
      mild. The most constant acute side effect of oxaliplatin observed in clinical
      trials was a transient peripheral neuropathy manifesting as paresthesia and
      dysesthesia in the extremities, triggered or enhanced by exposure to cold. The
      neurosensory phenomena, dependent on the cumulative dose of oxaliplatin, affect
      all patients who receive doses > or = 540 mg/m2 over four cycles or more of
      therapy. This neurologic toxicity is also highly reversible, with 82% of patients
      having their neuropathy regress within 4 to 6 months and 41% experiencing
      complete recovery within 6 to 8 months. With these considerations in mind, the
      currently recommended dosing schedules for oxaliplatin are 130 mg/m2/d as a 2- to
      6-hour infusion or 175 mg/m2/d as a chronomodulated infusion over 5 days, both of
      which are administered every 3 weeks. Oxaliplatin rapidly disappears from the
      plasma and is rapidly transformed into putative active species. 5-Fluorouracil
      and folinic acid, often used in combination with oxaliplatin, do not affect its
      pharmacokinetics. The favorable pharmacokinetics and safety profile of
      oxaliplatin contribute to its tolerability, particularly in pretreated cancer
      patients with reduced renal function. The reversible nature of its dose-limiting
      neurotoxicity and its synergistic action with 5-FU/FA make oxaliplatin an
      interesting agent for the treatment of colorectal cancer and for other potential
      indications.

PMID- 9609105
TI  - Clinical efficacy of oxaliplatin monotherapy: phase II trials in advanced
      colorectal cancer.
AB  - For the past 40 years, the mainstay of chemotherapy against colorectal cancer has
      been 5-fluorouracil (5-FU), often administered in recent years with folinic acid
      modulation. Traditional platinum derivatives have generally been ineffective in
      colorectal cancer therapy; however, the third-generation 1,2-diaminocyclohexane
      platinum derivative oxaliplatin has shown good antitumor activity and a lack of
      cross-reactivity with cisplatin. Oddly, oxaliplatin was first developed as a
      combination therapy with 5-FU plus folinic acid administered as a chronomodulated
      infusion over 5 days. In subsequent phase II clinical trials, the activity of
      single-agent oxaliplatin was assessed in 63 previously untreated patients and 139
      patients with metastatic disease refractory to 5-FU. In first-line therapy, the
      median overall survival was approximately 13 to 14 months, whereas in previously
      treated patients no longer responding to 5-FU, it was 8 to 10 months. The 18%
      objective response rate obtained with first-line therapy confirms that the
      activity of single-agent oxaliplatin is comparable to other anticancer therapies
      considered active against colorectal cancer. The 10% response rate obtained in
      second-line therapy in patients refractory to 5-FU provides a means for
      palliative care and suggests the possibility for a potentially active combination
      regimen with 5-FU.

PMID- 9609106
TI  - Oxaliplatin plus 5-fluorouracil: clinical experience in patients with advanced
      colorectal cancer.
AB  - Oxaliplatin was first introduced to the clinical setting as a combination therapy
      with 5-fluorouracil/folinic acid (5-FU/FA) in an attempt to improve the response
      rate obtained with 5-FU/FA against colorectal cancer. To dispel the impression
      that the improvements observed in objective response were somehow due to the
      chronomodulated regimen used, oxaliplatin was also tested in constant-rate
      infusion schedules and in regimens using bolus administration followed by 5-FU/FA
      infusion. The most current data comparing chronomodulated infusion and constant
      rate infusion in untreated patients show a lower objective response rate for the
      latter (51 % v 29%), but comparable median progression-free survival and median
      survival (9.8 months and 15.9 months v 7.9 months and 16.9 months, respectively).
      The first trials using constant-rate therapy included pretreated patients with
      metastatic colorectal cancer, most of whom were refractory to 5-FU. In these
      studies, conducted using two different regimens or variations of them, objective
      response rates < or = 46% were obtained. The addition of oxaliplatin to 5-FU/FA
      in controlled, randomized phase III trials has resulted in a twofold or greater
      increase in objective response rate and a 3-month gain in time to progression,
      with survival differences blurred by crossover effect. Compassionate-use programs
      that included many heavily pretreated relapsing patients reported response rates
      of 15% to 25%, confirming the value of the oxaliplatin-5-FU/FA regimen and
      suggesting that oxaliplatin may act synergistically with 5-FU.

PMID- 9609107
TI  - Reduction of nonresectable liver metastasis from colorectal cancer after
      oxaliplatin chemotherapy.
AB  - Until recently, approximately 30% of patients with resectable hepatic metastases
      from colorectal cancer survived 5 years after surgery. Additionally, many
      patients present with unresectable metastases and can look forward only to
      palliative care. Whereas therapeutic approaches such as cryosurgery appear to
      improve resectability, a key to resecting hepatic metastases is the ability to
      shrink the metastatic sites to make them more amenable to surgery. The
      administration of traditional chemotherapeutic modalities by conventional means
      or via intra-arterial or portal vein infusion has not provided significant
      improvements. The recent introduction of the combination oxaliplatin-5
      fluorouracil/folinic acid administered as a chronomodulated regimen, however, has
      provided better response rates with minimal toxicity. Recent results show that
      the resection of previously unresectable metastases became possible in up to 16%
      of patients after chemotherapy with a chronomodulated regimen of oxaliplatin plus
      5-fluorouracil/folinic acid. Of the patients who had successful resections, 54%
      and 40% were alive at 3 years and 5 years after surgery, respectively. The
      results of these studies demonstrate that this new approach can significantly
      prolong survival for patients with a previously bleak outlook. As a result, new
      treatment algorithms are evolving, integrating chemotherapeutic and surgical
      strategies for the treatment of patients with metastatic colorectal cancer.

PMID- 9609108
TI  - Oxaliplatin for the treatment of advanced colorectal cancer: future directions.
AB  - The introduction of oxaliplatin into the colorectal cancer setting represents a
      significant advancement in the treatment of the disease. Synergistic effects with
      traditional therapy 5-fluorouracil/folinic acid have increased response rates
      significantly, improved time-sensitive response parameters, and facilitated the
      removal of previously unresectable hepatic metastases, thus changing the natural
      history of the disease. Ongoing and planned trials are identifying various issues
      that need to be addressed to fully realize the potential of oxaliplatin. These
      include optimization of dosing and schedule of administration, determination of
      the most effective oxaliplatin-5-fluorouracil/folinic acid combination,
      definition of the role of new thymidylate synthase inhibitors with respect to
      oxaliplatin therapy, and identification of the most effective combinations of
      oxaliplatin with the new anticancer agents that have been recently introduced.
      Providing the answers to these questions will contribute to changing the attitude
      of the clinical oncologist regarding what strategy to adopt in treating
      colorectal cancer in the coming years.

PMID- 9609109
TI  - The IRS-signalling system: a network of docking proteins that mediate insulin
      action.
AB  - New molecules discovered during the past ten years have created a rational
      framework to understand signalling transduction by a broad range of growth
      factors and cytokines, including insulin. Insulin action is initiated through the
      insulin receptor, a transmembrane glycoprotein with intrinsic protein tyrosine
      kinase activity. The tyrosine kinase mediates the insulin response through
      tyrosine phosphorylation of various cellular substrates, in particular the IRS
      proteins. During insulin-stimulated tyrosine phosphorylation, the IRS-proteins
      mediate a broad biological response by binding and activating various enzymes or
      adapter molecules. Although we are far from a complete understanding of the
      insulin signalling system and its failure, enough pieces of the puzzle are
      falling into place that mechanism-based solutions to insulin resistance
      encountered with type II diabetes may soon be attainable.

PMID- 9609110
TI  - Role of binding proteins to IRS-1 in insulin signalling.
AB  - Insulin elicits its divergent metabolic and mitogenic effects by binding to its
      specific receptor, which belongs to the family of receptor tyrosine kinases. The
      activated insulin receptor phosphorylates the intracellular substrate IRS-1,
      which then binds various signalling molecules that contain SRC homology 2
      domains, thereby propagating the insulin signal. Among these IRS-1-binding
      proteins, the Grb2-Sos complex and the protein tyrosine phosphatase SHP-2
      transmit mitogenic signals through the activation of Ras, and phosphoinositide 3
      kinase is implicated in the major metabolic actions of insulin. Although
      substantial evidence indicates the importance of IRS-1 in insulin signal
      transduction, the generation of IRS-1-deficient mice has revealed the existence
      of redundant signalling pathways.

PMID- 9609111
TI  - Insulin regulation of the Ras activation/inactivation cycle.
AB  - In addition to mediating a number of metabolic functions, insulin also uses
      mitogenic pathways to maintain cellular homeostasis. Many of these mitogenic
      responses are mediated by signals through the small molecular weight guanine
      nucleotide binding protein, Ras. In the last decade, great progress has been made
      in understanding the molecular mechanisms which regulate the insulin mediated
      conversion of Ras from its inactive, GDP-bound state, to the activated GTP-bound
      form. More recently, it has been appreciated that insulin also regulates the
      inactivation of this pathway, namely by uncoupling the protein complexes whose
      formation is required for Ras activation. This review addresses molecular
      mechanism which both positively and negatively regulate this mitogenic signalling
      pathway.

PMID- 9609113
TI  - Protein phosphatase-1 and insulin action.
AB  - Protein Phosphatase-1 (PP-1) appears to be the key component of the insulin
      signalling pathway which is responsible for bridging the initial insulin
      simulated phosphorylation cascade with the ultimate dephosphorylation of insulin
      sensitive substrates. Dephosphorylations catalyzed by PP-1 activate glycogen
      synthase (GS) and simultaneously inactivate phosphorylase a and phosphorylase
      kinase promoting glycogen synthesis. Our in vivo studies using L6 rat skeletal
      muscle cells and freshly isolated adipocytes indicate that insulin stimulates PP
      1 by increasing the phosphorylation status of its regulatory subunit (PP-1G). PP
      1 activation is accompanied by an inactivation of Protein Phosphatase-2A (PP-2A)
      activity. To gain insight into the upstream kinases that mediate insulin
      stimulated PP-1G phosphorylation, we employed inhibitors of the ras/MAPK, PI3
      kinase, and PKC signalling pathways. These inhibitor studies suggest that PP-1G
      phosphorylation is mediated via a complex, cell type specific mechanism involving
      PI3-kinase/PKC/PKB and/or the ras/MAP kinase/Rsk kinase cascade. cAMP agonists
      such as SpcAMP (via PKA) and TNF-alpha (recently identified as endogenous
      inhibitor of insulin action via ceramide) block insulin-stimulated PP-1G
      phosphorylation with a parallel decrease of PP-1 activity, presumably due to the
      dissociation of the PP-1 catalytic subunit from the regulatory G-subunit. It
      appears that any agent or condition which interferes with the insulin-induced
      phosphorylation and activation of PP-1, will decrease the magnitude of insulin's
      effect on downstream metabolic processes. Therefore, regulation of the PP-1G
      subunit by site-specific phosphorylation plays an important role in insulin
      signal transduction in target cells. Mechanistic and functional studies with cell
      lines expressing PP-1G subunit site-specific mutations will help clarify the
      exact role and regulation of PP-1G site-specific phosphorylations on PP-1
      catalytic function.

PMID- 9609112
TI  - Insulin signal transduction through protein kinase cascades.
AB  - This review summarizes the evolution of ideas concerning insulin signal
      transduction, the current information on protein ser/thr kinase cascades as
      signalling intermediates, and their status as participants in insulin regulation
      of energy metabolism. Best characterized is the Ras-MAPK pathway, whose input is
      crucial to cell fate decisions, but relatively dispensable in metabolic
      regulation. By contrast the effectors downstream of PI-3 kinase, although less
      well elucidated, include elements indispensable for the insulin regulation of
      glucose transport, glycogen and cAMP metabolism. Considerable information has
      accrued on PKB/cAkt, a protein kinase that interacts directly with Ptd Ins 3'OH
      phosphorylated lipids, as well as some of the elements further downstream, such
      as glycogen synthase kinase-3 and the p70 S6 kinase. Finally, some information
      implicates other erk pathways (e.g. such as the SAPK/JNK pathway) and Nck/cdc42
      regulated PAKs (homologs of the yeast Ste 20) as participants in the cellular
      response to insulin. Thus insulin recruits a broad array of protein (ser/thr)
      kinases in its target cells to effectuate its characteristic anabolic and
      anticatabolic programs.

PMID- 9609114
TI  - Insulin receptor internalization and signalling.
AB  - The insulin receptor kinase (IRK) is a tyrosine kinase whose activation,
      subsequent to insulin binding, is essential for insulin-signalling in target
      tissues. Insulin binding to its cell surface receptor is rapidly followed by
      internalization of insulin-IRK complexes into the endosomal apparatus (EN) of the
      cell. Internalization of insulin into target organs, especially liver, is
      implicated in effecting insulin clearance from the circulation. Internalization
      mediates IRK downregulation and hence attenuation of insulin sensitivity although
      most internalized IRKs readily recycle to the plasma membrane at physiological
      levels of insulin. A role for internalization in insulin signalling is indicated
      by the accumulation of activated IRKs in ENs. Furthermore, the maximal level of
      IRK activation has been shown to exceed that attained at the cell surface. Using
      an in vivo rat liver model in which endosomal IRKs are exclusively activated has
      revealed that IRKs at this intracellular locus are able by themselves to promote
      IRS-1 tyrosine phosphorylation and induce hypoglycemia. Furthermore, studies with
      isolated rat adipocytes reveal the EN to be the principle site of insulin
      stimulated IRS-1 tyrosine phosphorylation and associated PI3K activation. Key
      steps in the termination of the insulin signal are also operative in ENs. Thus,
      an endosomal acidic insulinase has been identified which limits the extent of IRK
      activation. Furthermore, IRK dephosphorylation is effected in ENs by an
      intimately associated phosphotyrosine phosphatase(s) which, in rat liver, appears
      to regulate IRK activity in both a positive and negative fashion. Thus, insulin
      mediated internalization of IRKs into ENs plays a crucial role in effecting and
      regulating signal transduction in addition to modulating the levels of
      circulating insulin and the cellular concentration of IRK in target tissues.

PMID- 9609115
TI  - Spatial determinants of specificity in insulin action.
AB  - Insulin is a potent stimulator of intermediary metabolism, however the basis for
      the remarkable specificity of insulin's stimulation of these pathways remains
      largely unknown. This review focuses on the role compartmentalization plays in
      insulin action, both in signal initiation and in signal reception. Two examples
      are discussed: (1) a novel signalling pathway leading to the phosphorylation of
      the caveolar coat protein caveolin, and (2) a recently identified scaffolding
      protein, PTG, involved directly in the regulation of enzymes controlling glycogen
      metabolism.

PMID- 9609116
TI  - Binding of SH2 containing proteins to the insulin receptor: a new way for
      modulating insulin signalling.
AB  - Prior studies have established a role in insulin action for the tyrosine
      phosphorylation of substrates and their subsequent complexing with SH2 containing
      proteins. More recently, SH2 proteins have been identified which can tightly bind
      to the tyrosine phosphorylated insulin receptor. The major protein identified so
      far (called Grb-IR or Grb10) of this type appears to be present in at least 3
      isoforms, varying in the presence of a pleckstrin homology domain and in the
      sequence of its amino terminus. The binding of this protein to the insulin
      receptor appears to inhibit signalling by the receptor. The present review will
      discuss the current knowledge of the structure and function of this protein.

PMID- 9609117
TI  - Insulin receptor-associated protein tyrosine phosphatase(s): role in insulin
      action.
AB  - Protein tyrosine phosphatases (PTPs) play a critical role in regulating insulin
      action in part through dephosphorylation of the active (autophosphorylated) form
      of the insulin receptor (IRK) and attenuation of its tyrosine kinase activity.
      Following insulin binding the activated IRK is rapidly internalized into the
      endosomal apparatus, a major site at which the IRK is dephosphorylated in vivo.
      Studies in rat liver suggest a complex regulatory process whereby PTPs may act,
      via selective IRK tyrosine dephosphorylation, to modulate IRK activity in both a
      positive and negative manner. Use of peroxovanadium (pV) compounds, shown to be
      powerful PTP inhibitors, has been critical in delineating a close relationship
      between the IRK and its associated PTP(s) in vivo. Indeed the in vivo
      administration of pV compounds effected activation of IRK in parallel with an
      inhibition of IRK-associated PTP activity. This process was accompanied by a
      lowering of blood glucose levels in both normal and diabetic rats thus
      implicating the IRK-associated PTP(s) as a suitable target for defining a novel
      class of insulin mimetic agents. Identification of the physiologically relevant
      IRK-associated PTP(s) should facilitate the development of drugs suitable for
      managing diabetes mellitus.

PMID- 9609119
TI  - Protein-tyrosine phosphatase-1B acts as a negative regulator of insulin signal
      transduction.
AB  - Insulin signaling involves a dynamic cascade of protein tyrosine phosphorylation
      and dephosphorylation. Most of our understanding of this process comes from
      studies focusing on tyrosine kinases, which are signal activators. Our knowledge
      of the role of protein-tyrosine phosphatases (PTPases), signal attenuators, in
      regulating insulin signal transduction remains rather limited. Protein-tyrosine
      phosphatase 1B (PTP-1B), the prototypical PTPase, is ubiquitously and abundantly
      expressed. Work from several laboratories, including our own, has implicated PTP
      1B as a negative regulator of insulin action and as a potentially important
      mediator in the pathogenesis of insulin-resistance and non-insulin dependent
      diabetes mellitus (NIDDM).

PMID- 9609118
TI  - Regulation of the insulin signalling pathway by cellular protein-tyrosine
      phosphatases.
AB  - Protein-tyrosine phosphatases (PTPases) have been implicated in the physiological
      regulation of the insulin signalling pathway. In cellular and molecular studies,
      the transmembrane, receptor-type PTPase LAR and the intracellular, non-receptor
      enzyme PTP1B have been shown to have a direct impact on insulin action in intact
      cell models. Since insulin signalling can be enhanced by reducing the abundance
      or activity of specific PTPases, pharmaceutical agents directed at blocking the
      interaction between individual PTPases and the insulin receptor may have
      potential clinical relevance to the treatment of insulin-resistant states such as
      obesity and Type II diabetes mellitus.

PMID- 9609120
TI  - Multifunctional actions of vanadium compounds on insulin signaling pathways:
      evidence for preferential enhancement of metabolic versus mitogenic effects.
AB  - The pathophysiologic importance of insulin resistance in diseases such as obesity
      and diabetes mellitus has led to great interest in defining the mechanism of
      insulin action as well as the means to overcome the biochemical defects
      responsible for the resistance. Vanadium compounds have been discovered to mimic
      many of the metabolic actions of insulin both in vitro and in vivo and improve
      glycemic control in human subjects with diabetes mellitus. Apart from its direct
      insulinmimetic actions, we found that vanadate modulates insulin metabolic
      effects by enhancing insulin sensitivity and prolonging insulin action. All of
      these actions appear to be related to protein tyrosine phosphatase (PTP)
      inhibition. However, in contrast to its stimulatory effects, vanadate inhibits
      basal and insulin-stimulated system A amino acid uptake and cell proliferation.
      The mechanism of these actions also appears to be related to PTP inhibition,
      consistent with the multiple roles of PTPs in regulating signal transduction.
      While the precise biochemical pathway of vanadate action is not yet known, it is
      clearly different from that of insulin in that the insulin receptor and
      phosphatidylinositol 3'-kinase do not seem to be essential for vanadate
      stimulation of glucose uptake and metabolism. The ability of vanadium compounds
      to 'bypass' defects in insulin action in diseases characterized by insulin
      resistance and their apparent preferential metabolic versus mitogenic signaling
      profile make them attractive as potential pharmacological agents.

PMID- 9609121
TI  - Regulation of the Na+/K+-ATPase by insulin: why and how?
AB  - The sodium-potassium ATPase (Na+/K+-ATPase or Na+/K+-pump) is an enzyme present
      at the surface of all eukaryotic cells, which actively extrudes Na+ from cells in
      exchange for K+ at a ratio of 3:2, respectively. Its activity also provides the
      driving force for secondary active transport of solutes such as amino acids,
      phosphate, vitamins and, in epithelial cells, glucose. The enzyme consists of two
      subunits (alpha and beta) each expressed in several isoforms. Many hormones
      regulate Na+/K+-ATPase activity and in this review we will focus on the effects
      of insulin. The possible mechanisms whereby insulin controls Na+/K+-ATPase
      activity are discussed. These are tissue- and isoform-specific, and include
      reversible covalent modification of catalytic subunits, activation by a rise in
      intracellular Na+ concentration, altered Na+ sensitivity and changes in subunit
      gene or protein expression. Given the recent escalation in knowledge of insulin
      stimulated signal transduction systems, it is pertinent to ask which
      intracellular signalling pathways are utilized by insulin in controlling Na+/K+
      ATPase activity. Evidence for and against a role for the phosphatidylinositol-3
      kinase and mitogen activated protein kinase arms of the insulin-stimulated
      intracellular signalling networks is suggested. Finally, the clinical relevance
      of Na+/K+-ATPase control by insulin in diabetes and related disorders is
      addressed.

PMID- 9609122
TI  - Potential mechanism(s) involved in the regulation of glycogen synthesis by
      insulin.
AB  - Stimulation of glycogen synthesis is one of the major physiological responses
      modulated by insulin. Although, details of the precise mechanism by which insulin
      action on glycogen synthesis is mediated remains uncertain, significant advances
      have been made to understand several steps in this process. Most importantly,
      recent studies have focussed on the possible role of glycogen synthase kinase-3
      (GSK-3) and glycogen bound protein phosphatase-1 (PP-1G) in the activation of
      glycogen synthase (GS) - a key enzyme of glycogen metabolism. Evidence is also
      accumulating to establish a link between insulin receptor induced signaling
      pathway(s) and glycogen synthesis. This article summarizes the potential
      contribution of various elements of insulin signaling pathway such as mitogen
      activated protein kinase (MAPK), protein kinase B (PKB), and phosphatidyl
      inositol 3-kinase (PI3-K) in the activation of GS and glycogen synthesis.

PMID- 9609123
TI  - Metabolic and therapeutic lessons from genetic manipulation of GLUT4.
AB  - This review focuses on the effects of varying levels of GLUT4, the insulin
      sensitive glucose transporter, on insulin sensitivity and whole body glucose
      homeostasis. Three mouse models are discussed including MLC-GLUT4 mice which
      overexpress GLUT4 specifically in skeletal muscle, GLUT4 null mice which express
      no GLUT4, and the MLC-GLUT4 null mice which express GLUT4 only in skeletal
      muscle. Overexpressing GLUT4 specifically in the skeletal muscle results in
      increased insulin sensitivity in the MLC-GLUT4 mice. In contrast, the GLUT4 null
      mice exhibit insulin intolerance accompanied by abnormalities in glucose and
      lipid metabolism. Restoring GLUT4 expression in skeletal muscle in the MLC-GLUT4
      null mice results in normal glucose metabolism but continued abnormal lipid
      metabolism. The results of experiments using these mouse models demonstrates that
      modifying the expression of GLUT4 profoundly affects whole body insulin action
      and consequently glucose and lipid metabolism.

PMID- 9609124
TI  - Insulin action in skeletal muscle from patients with NIDDM.
AB  - Insulin resistance in peripheral tissues is a common feature of non insulin
      dependent diabetes mellitus (NIDDM). The decrease in insulin-mediated peripheral
      glucose uptake in NIDDM patients can be localized to defects in insulin action on
      glucose transport in skeletal muscle. Following short term in vitro exposure to
      both submaximal and maximal concentrations of insulin, 3-O-methylglucose
      transport rates are 40-50% lower in isolated skeletal muscle strips from NIDDM
      patients when compared to muscle strips from nondiabetic subjects. In addition,
      we have shown that physiological levels of insulin induce a 1.6-2.0 fold increase
      in GLUT4 content in skeletal muscle plasma membranes from control subjects,
      whereas no significant increase was noted in NIDDM skeletal muscle. Impaired
      insulin-stimulated GLUT4 translocation and glucose transport in NIDDM skeletal
      muscle is associated with reduced insulin-stimulated IRS-1 tyrosine
      phosphorylation and PI3-kinase activity. The reduced IRS-1 phosphorylation cannot
      be attributed to decreased protein expression, since the IRS-1 protein content is
      similar between NIDDM subjects and controls. Altered glycemia may contribute to
      decreased insulin-mediated glucose transport in skeletal muscle from NIDDM
      patients. We have shown that insulin-stimulated glucose transport is normalized
      in vitro in the presence of euglycemia, but not in the presence of hyperglycemia.
      Thus, the circulating level of glucose may independently regulate insulin
      stimulated glucose transport in skeletal muscle from NIDDM patients via a down
      regulation of the insulin signaling cascade.

PMID- 9609125
TI  - Genetic manipulation of insulin action and beta-cell function in mice.
AB  - Transgenic and gene targeting approaches have now been applied to a number of
      genes in order to investigate the metabolic disorders that would result by
      manipulating insulin action or pancreatic beta-cell function in the mouse. The
      availability of such mutant mice will allow in the future to develop animal
      models in which the pathophysiologies resulting from polygenic defects might be
      reconstituted and studied in detail. Such animal models hopefully will lead to
      better understanding of complex polygenic diseases such as non-insulin-dependent
      diabetes mellitus (NIDDM).

PMID- 9609126
TI  - TNF-alpha and insulin resistance: summary and future prospects.
AB  - While the causes of obesity remain elusive, the relationship between obesity and
      insulin resistance is a well-established fact [1]. Insulin resistance is defined
      as a smaller than normal response to a certain dose of insulin, and contributes
      to several pathological problems of obese patients such as hyperlipidemia,
      arteriosclerosis and hypertension. Several pieces of evidence indicate that the
      cytokine tumor necrosis factor a (TNF-alpha) is an important player in the state
      of insulin resistance observed during obesity. In this review we will try to
      summarize what is known about the function of TNF-alpha in insulin resistance
      during obesity and how TNF-alpha interferes with insulin signaling.

PMID- 9609127
TI  - Membrane glycoprotein PC-1 and insulin resistance.
AB  - Peripheral resistance to insulin is a major component of non-insulin dependent
      diabetes mellitus. Defects in insulin receptor tyrosine kinase activity have been
      demonstrated in several tissues from insulin resistant subjects, but mutations in
      the insulin receptor gene occur in only a small fraction of cases. Therefore,
      other molecules that are capable of modulating the function of the insulin
      receptor are likely candidates in the search for the cellular mechanisms of
      insulin resistance. We have isolated an inhibitor of insulin receptor tyrosine
      kinase activity from cultured fibroblasts of an insulin resistant NIDDM patient
      and identified it as membrane glycoprotein PC-1. Subsequently we have
      demonstrated that expression of PC-1 is elevated in fibroblasts from other
      insulin resistant subjects, both with and without NIDDM. Studies in muscle, the
      primary site for insulin-mediated glucose disposal, have shown that the levels of
      PC-1 in this tissue are inversely correlated to insulin action both in vivo and
      in vitro. Transfection of PC-1 into cultured cells has confirmed that
      overexpression of PC-1 can produce impairments in insulin receptor tyrosine
      kinase activity and the subsequent cellular responses to insulin. Preliminary
      data suggests a direct interaction between PC-1 and the insulin receptor.
      However, the mechanisms whereby PC-1 inhibits insulin receptor signaling remain
      to be determined.

PMID- 9609128
TI  - Insulin action on protein phosphatase-1 activation is enhanced by the
      antidiabetic agent pioglitazone in cultured diabetic hepatocytes.
AB  - Effect of the antidiabetic agent pioglitazone on the insulin-mediated activation
      of protein phosphatase-1 was examined in diabetic hepatocytes. Streptozotocin
      induced diabetes in Sprague Dawley rats caused a significant decrease in the
      activation of glycogen synthase in hepatocytes isolated from these animals. There
      was an inverse correlation between the in vivo hyperglycemic condition and the in
      vitro activation of glycogen synthase in liver cells (r = 0.93, p < 0.001). Long
      term incubation of diabetic hepatocytes with insulin and dexamethasone caused
      significant (p < 0.001) improvement in the activation of glycogen synthase
      activation. When incubated along with hormones, pioglitazone enhanced their
      action (p < 0.05-0.01). Diabetic hepatocytes were also characterized by 50%
      decrease in the activity of protein phosphatase-1, the enzyme which
      dephosphorylates and activates glycogen synthase. Pioglitazone potentiated the
      acute stimulatory effect of insulin on protein phosphatase-1 in normal
      hepatocytes but not in diabetic hepatocytes. Long term incubation of diabetic
      hepatocytes with insulin ameliorated the decrease in the protein phosphatase-1
      activity in these cells. This stimulatory long-term effect of insulin was
      significantly (p < 0.05) enhanced by the antidiabetic agent pioglitazone.

PMID- 9609129
TI  - Flexibility of the thyroiditogenic T cell repertoire for murine autoimmune
      thyroiditis in CD8-deficient (beta2m -/-) and T cell receptor Vbeta(c) congenic
      mice.
AB  - In murine experimental autoimmune thyroiditis (EAT), previous studies have
      revealed a highly adaptable thyroiditogenic T cell repertoire which involves both
      CD4+ and CD8+ T cells in the susceptible H2k strain. To further test this
      flexibility, congenic B10.K mice lacking CD8+ T cells (B2m -/-) or harboring 70%
      T cell receptor (TCR) Vbeta gene deletions (Vbeta(c)) were immunized with mouse
      thyroglobulin (MTg) and evaluated for EAT 28 days later. All B2m -/- mice
      developed moderate antibodies to MTg, and thyroidal inflammation was comparable
      to B10.K mice, averaging 35-40%. Spleen cells (SC) from MTg-immunized mice were
      then injected into syngeneic recipients after stimulation in vitro with MTg or
      with conserved, thyroxine (T4)- or thyronine (T0)- containing 12mer peptides,
      hT4(5), hT0(2553), or hT4(2553), derived from the primary hormonogenic sites at
      position 5 or 2553 of human Tg. As previously shown in another H2k strain
      (CBA/J), all three peptides activated MTg-primed SC to transfer EAT in B10.K
      mice. hT4(5) and hT4(2553) were further tested in B10.K-Vbeta(c) and beta2m-
      B10.K mice. Both peptides expanded thyroiditogenic T cells in either strain,
      resulting in severe thyroiditis in syngeneic recipients. That EAT can develop in
      the absence of CD8+ T cells or in the presence of a severely restricted TCR
      repertoire underscores the remarkable flexibility of the thyroiditogenic T cell
      profile in the susceptible k haplotype.

PMID- 9609130
TI  - Cyclosporine induced autoimmunity in newborns prevented by early immunization.
AB  - It has been shown in animal toxicity models that administration of Cyclosporine,
      CsA, to a pregnant mouse greatly increases the risk that the offspring will
      develop autoimmunity. Immunization starting at birth has been shown to prevent
      autoimmunity in other animal models of autoimmunity and early immunization is
      associated with the prevention of diabetes in humans. Experiments were performed
      to see if early immunization could also prevent CsA induced autoimmunity. Mice
      were injected with CsA during the first week of life and then immunized with
      killed human vaccines, including common pediatric vaccines, starting in the
      second week of life for a total of 3-4 doses. Administration of CsA during the
      first week of life resulted in the development of antigastric autoantibodies
      which were measured at week 8 of life. Only 12% of mice treated with CsA alone
      lacked anti-agastric antibodies compared to 61% in the group receiving the CsA
      and the diphtheria, tetanus, pertussis, and anthrax vaccines (p = 0.0005). The
      results indicate early immunization can prevent CsA induced autoimmunity and
      provide further evidence that the effect of starting immunization in the first
      month should be compared to starting immunization after 2 months in humans.

PMID- 9609131
TI  - Antiphospholipid antibodies: a new risk factor for restenosis after percutaneous
      transluminal coronary angioplasty?
AB  - Antiphospholipid antibodies (aPL) have been found to be associated with arterial
      and venous thrombosis. Percutaneous transluminal coronary angioplasty (PTCA) is
      an established therapy for ischaemic heart disease (IHD), which is still affected
      by restenosis at a rate of 20-30%. This study was aimed at investigating the
      possible role of aPL in restenosis after PTCA. In sixty consecutive IHD patients,
      aPL (lupus anticoagulant -LA- and anticardiolipin antibodies -aCL) and markers of
      haemostatic activation were investigated before PTCA, and patients were followed
      up for restenosis. No infections, autoimmune disease or treatment by drugs that
      may alter aPL levels occurred in any of the patients. aPL were found in 15/60
      patients: aCL in 7/60, LA in 5/60 and aCL and LA in 3/60. No statistically
      significant difference was found between aPL negative and aPL positive patients
      in pre PTCA plasma levels of prothrombin activation fragment (F1+2) 1.4 nmol/l
      (0.3-5.71) vs 1.4 nmol/l (0.9-4.0), thrombin-antithrombin complex (TAT) 4.0
      microg/l (1.1-34.2) vs 5.2 microg/l (2.1-60.0), D-dimer (DD) 25 ng/ml (2-515) vs
      44 ng/ml (2-160) or plasminogen activator inhibitor activity (PAI) 4.8 IU/ml (2.5
      36.4) vs 4.4 IU/ml (2.5-13.4). Restenosis was observed in 13/60 patients (7/45
      15% - aPL negative and 6/15-40% - aPL positive patients) who underwent
      angiographic tests after PTCA because of recurring angina or positive exercise
      test. Restenosis occurred after 2.2 months (0.5-3) in aPL positive patients and
      after 3.5 months (1-12.8) in aPL negative. These results suggest that 1)
      restenosis with recurrent ischaemia occurs more frequently in aPL positive than
      in aPL negative patients, 2) in aPL positive patients restenosis occurs earlier,
      and 3) the presence of aPL is not associated with hypercoagulability.

PMID- 9609132
TI  - Evidence for carbimazole as an antioxidant?
AB  - There is evidence in the literature to support the view that antioxidants are
      involved in the pathogenesis of Graves disease and that antioxidants may act as
      free radical scavengers. This study has compared the effects of a 12 month course
      of conventional Carbimazole therapy on peripheral blood antioxidant levels with
      those of a 12 month course of a higher dose treatment regime. Fifty seven
      patients were enrolled into the study. Those in Group 1 (n = 23) received a 12
      month course of 60 mg/day Carbimazole. Those in Group 2 (n = 34) received 45
      mg/day for the first month, 30 mg/day for the second and 20 mg/day for the
      remaining 10 months of treatment. T3 was added in both groups after 2-4 months to
      maintain patients euthyroid. Baseline samples were also obtained from 30 control
      subjects. Blood samples were taken for the measurement of plasma thiol (PSH),
      lysate thiol (LSH), superoxide dismutase (SOD) and caeruloplasmin (CP) and for
      routine thyroid function tests (TT4, TT3 and TSH). In untreated Graves' patients,
      serum levels of PSH and SOD were reduced and levels of LSH increased compared to
      controls. Following 2 months high dose Carbimazole therapy there was a
      significant increase in PSH levels and a significant reduction in CP levels
      compared to presentation levels. In the more conventional dose Group 2 patients
      PSH levels also rose significantly during the first 2 months of treatment. Levels
      for both groups were still significantly lower than the control group. After 12
      months high dose Carbimazole therapy PSH levels had decreased so that they no
      longer differed from untreated levels. LSH and SOD levels still remained
      abnormal. CP levels continued to fall. Similar findings were obtained in those
      patients receiving the more conventional course of treatment. At no point was
      their any significant difference in antioxidant levels between the two treatment
      groups. The abnormal levels of antioxidants in the serum of untreated Graves'
      patients confirm their involvement in the pathogenesis of Graves' disease.
      Carbimazole therapy appeared to have only short term effects on the peripheral
      blood levels of the antioxidants measured. Carbimazole appeared to act only on
      the extra cellular markers of antioxidant activity (PSH, CP) although the disease
      itself had marked intracellular effects (LSH, SOD). These findings suggest that
      Carbimazole does not act as a free radical scavenger.

PMID- 9609133
TI  - Plasma and synovial fluid soluble CD23 concentrations in children with juvenile
      chronic arthritis.
AB  - Since increased levels of sCD23 were demonstrated in patients with autoimmune
      diseases, plasma and synovial fluid sCD23 levels were examined in 22 patients
      with juvenile chronic arthritis (JCA) and in 10 children undergoing
      arthrocentesis for orthopedic disorders. There was no significant difference in
      plasma sCD23 concentrations between patients with pauciarticular and
      polyarticular onset. Plasma and synovial fluid sCD23 concentrations were found to
      be significantly increased in JCA patients as compared to controls. However,
      plasma sCD23 levels were not positively correlated with laboratory parameters
      showing disease activity such as erythrocyte sedimentation rate, C-reactive
      protein, serum IgG and IgA. It was concluded that increased production of sCD23
      in peripheral blood and synovial fluid might be important in the pathogenesis of
      JCA. However, determination of this immunological parameter provides no useful
      clinical information about disease activity and management.

PMID- 9609134
TI  - Autoimmune diabetes: the role of T cells, MHC molecules and autoantigens.
AB  - Type 1 diabetes (IDDM) is a T cell mediated autoimmune disease which in part is
      determined genetically by its association with major histocompatibility complex
      (MHC) class II alleles. The major role of MHC molecules is the regulation of
      immune responses through the presentation of peptide epitopes of processed
      protein antigens to the immune system. Recently it has been demonstrated that MHC
      molecules associated with autoimmune diseases preferentially present peptides of
      other endogenous MHC proteins, that often mimic autoantigen-derived peptides.
      Hence, these MHC-derived peptides might represent potential targets for
      autoreactive T cells. It has consistently been shown that humoral autoimmunity to
      insulin predominantly occurs in early childhood. The cellular immune response to
      insulin is relatively low in the peripheral blood of patients with IDDM. Studies
      in NOD mice however have shown, that lymphocytes isolated from pancreatic islet
      infiltrates display a high reactivity to insulin and in particular to an insulin
      peptide B 9-23. Furthermore we have evidence that cellular autoimmunity to
      insulin is higher in young pre-diabetic individuals, whereas cellular reactivity
      to other autoantigens is equally distributed in younger and older subjects. This
      implicates that insulin, in human childhood IDDM and animal autoimmune diabetes,
      acts as an important early antigen which may target the autoimmune response to
      pancreatic beta cells. Moreover, we observed that in the vast majority of newly
      diagnosed diabetic patients or individuals at risk for IDDM, T cell reactivity to
      various autoantigens occurs simultaneously. In contrast, cellular reactivity to a
      single autoantigen is found with equal frequency in (pre)-type 1 diabetic
      individuals as well as in control subjects. Therefore the autoimmune response in
      the inductive phase of IDDM may be targeted to pancreatic islets by the cellular
      and humoral reactivity to one beta-cell specific autoantigen, but spreading to a
      set of different antigens may be a prerequisite for progression to destructive
      insulitis and clinical disease. Due to mimic epitopes shared by autoantigen(s),
      autologous MHC molecules and environmental antigens autoimmunity may spread,
      intramolecularly and intermolecularly and amplify upon repeated reexposure to
      mimic epitopes of environmental triggers.

PMID- 9609135
TI  - The APC1 concept of type I diabetes.
AB  - Type I diabetes appears to be a T cell dependent disease. T cell reactivity is
      regulated by antigen presenting cells (APCs). In animal models of type I
      diabetes, abnormal reactivity of APCs, in particular of macrophages, probably is
      responsible for the progression of islet inflammation from T helper type 2
      dependent benign periinsulitis to T helper type I dependent destructive
      intrainsulitis. The functional state of APCs during preferential stimulation of
      Th1 reactivities (APC1 state) is characterized by the release of TNFalpha, IL-12
      and/or IL-18. The bias towards APC1 reactivity has been found due to defective
      inhibition via IL-10 and PGE2.

PMID- 9609136
TI  - Hypothesis: interleukin-5 production impairment can be a key point in the
      pathogenesis of the MHC-linked selective IgA deficiency.
AB  - Selective IgA deficiency (IgA-D) is associated with the expression of some human
      leukocyte antigens (HLA) haplotypes and Major Hystocompatibility Complex (MHC)
      gene products have been suggested to be involved in the regulation of IgA
      synthesis. Recently, we have obtained evidences indicating that MHC influences
      the production of IgA and interleukin-5 (IL-5) both in humans and in mice.
      Lymphnode cells from pychril chloride (PC1) immunised BALB/c mice (bearing the H
      2d haplotype) fail to produce IL-5 when stimulated in vitro with PC1 and this
      correlates with low antigen specific IgA production in vivo. In contrast using
      congenic BALB/k mice (bearing the H-2k haplotype) an high production both of IL-5
      and of PC1-specific IgA is observed. Moreover, in vivo or in vitro administration
      of IL-5 to BALB/c mice was able to increase the production of antigen specific
      IgA. Similar evidences have been obtained by evaluation of the HLA influence on
      circulating immunoglobulin levels and interleukin production in normal HLA typed
      subjects. In fact HLA-B8, DR3 positive subjects show reduced level of serum IgA
      and their peripheral blood mononuclear cells stimulated with mitogen produce
      significantly reduced amounts of IL-5, IL-12, IL-2 and Interferon-gamma. We
      hypothesise that HLA-B8, DR3 associated IgA deficiency, known to be asymptomatic,
      can be due to a lack of subsequent signals, in particular of IL-5, involved in
      the late regulation of B cell differentiation. Preliminary evidences
      demonstrating that low amounts of human recombinant IL-5 are able to reconstitute
      IgA production by cells from HLA-B8, DR3 IgA-D subjects, seem to confirm this
      hypothesis.

PMID- 9609137
TI  - Histamine-containing mast cells and their relationship to NGFr-immunoreactive
      nerves in prurigo nodularis: a reappraisal.
AB  - The mast cell, which is a histamine-containing cell, has been found to have far
      more functions in skin inflammation than hitherto understood. To investigate the
      appearance of mast cells in prurigo nodularis, histamine immunohistochemistry in
      combination with nerve growth factor receptor (NGFr) double-staining as well as
      electron microscopic studies were performed. The results revealed that the
      histamine-containing cell number was increased in the lesional dermis. The mast
      cell size was also increased and the shape had become more dendritic. They tended
      to contact the epidermis and even infiltrated into it. In the histamine and NGFr
      double-staining, both an increased histamine-containing mast cell number and an
      increased number of NGFr-immunoreactive nerve fiber profiles were revealed in the
      upper dermis of the prurigo nodularis lesional skin. Mast cells were seen in
      close vicinity to NGFr-positive nerves and sometimes even seemingly to contact
      single nerve fibers. At the ultrastructural level, it is obvious that the mast
      cell bodies become larger, having more abundant cytoplasm and organelles (e.g.
      mitochondria), but comparatively fewer characteristic granules. Mast cells were
      often observed to sprout long dendrites, with or without granules. The cells were
      also frequently seen to contact other cell types, and a mast cell infiltration
      into the epidermis was also found. The statistical results of mast cell numbers
      showed a significant increase in prurigo nodularis lesional skin compared to the
      normal controls. The present results further indicate that mast cells, together
      with cutaneous nerve fibers, are actively involved in the pathogenesis of the
      disease.

PMID- 9609138
TI  - CD44 and variants in melanocytic skin neoplasms.
AB  - Expression of cell surface molecules that mediate cell-matrix and cell-cell
      interactions largely contributes to the ability of melanoma cells to migrate and
      spread beyond the primary site of the tumor. CD44, the principal cell-surface
      receptor for hyaluronate, and its numerous splice variants have been reported to
      play a crucial role in invasion and the metastatic process of different human
      neoplasms, including primary malignant melanoma (PMM). The aim of this study was
      to clarify which isoforms of CD44 (standard CD44 and CD44 variants) are
      distributed in PMM with a vertical tumor thickness of >1.4 mm. Staining of CD44
      standard (CD44s) and splice variants was further examined for diagnostic and
      prognostic relevance in a panel of melanocytic skin lesions. Ten cases of PMM
      with Breslow >1.4 mm were analysed by immunohistochemistry using monoclonal
      antibodies specific for CD44s and the splice variants v3, v5, v6, v7, v7-8, and
      v10. In addition, using anti-CD44s, v5, and v6 antibodies, 55 melanocytic
      lesions, including dermal nevi (n=12), Clark nevi (dysplastic nevi) (CN; n=11),
      melanoma in situ (Mis; n=8), PMM (n=18), and cutaneous metastasis of malignant
      melanoma (cMMM; n=6) were assessed. Staining intensities were scored visually and
      evaluated by means of a staining index. In ten cases of PMM with a Breslow index
      >1.4 mm positive staining was ascertained for CD44s, v5 and for v6 in three
      cases. No staining was found for v3, v7, v7-8, and v10. Examination of CD44s, v5,
      and v6 in 55 melanocytic skin lesions revealed a high index for CD44s in all
      specimens and a weak staining of v5 in Mis; dermal nevi and CN did not stain for
      v5. However, in PMM and cMMM we found v5 to be strongly positive. The isoform v6
      showed a variable index only in PMM, but without connection to established
      prognostic criteria. We conclude that CD44s and splice variants can not be
      regarded as indicators for tumor progression in malignant melanomas. However, v5
      may potentially serve as a diagnostic marker for melanocytic skin lesions.

PMID- 9609139
TI  - Tyrosinase immunoreactivity in formalin-fixed, paraffin-embedded primary and
      metastatic melanoma: frequency and distribution.
AB  - Monoclonal antibody T311 specifically detects tyrosinase protein expression.
      Tyrosinase-derived peptides are recognized by CD8+ T-cells and applied in
      immunotherapy. We examined formalin-fixed paraffin-embedded tissue of 50 melanoma
      (primary n=31, metastatic n=19) and 41 control cases (junctional, dermal,
      compound, Spitz, Reed, balloon-cell nevi) by immunochemistry using the alkaline
      phosphatase-anti-alkaline phosphatase method after antigen retrieval. Staining
      with mAb T311 showed a sensitivity of 94% for melanoma with a very high
      specificity for melanocytic cells. Immunopositivity (94% of melanomas overall)
      correlated inversely with clinical stage: clinical stage I and stage II showed
      100%, stage III and stage IV 86% immunoreactivity each. Staining changed from an
      exclusively homogeneous pattern in early stages to a more heterogeneous pattern
      in later stages. Melanocytic control tissue like nevi of different subtypes all
      showed weak to moderate, homogeneous immunoreactivity with polarity towards the
      epidermis. RT-PCR ELISA analysis of short-term melanoma cell cultures displayed
      mRNA expression in only half of the originally immunopositive tumors only,
      suggesting rapid mRNA expression loss in culture. mAb T311 allows detection of
      melanoma-associated tyrosinase protein expression and thus profiling of melanomas
      using routine archival tissue suited for immunotherapy approaches involving
      tyrosinase derived epitopes.

PMID- 9609140
TI  - The lymphocytic infiltrate in acute cutaneous allogeneic graft-versus-host
      reactions lacks evidence for phenotypic restriction in donor-derived cells.
AB  - The lymphocytic subtypes effecting allogeneic graft-versus-host disease (GVHD)
      are unknown. We studied 35 skin biopsy specimens from 19 women transplanted with
      bone marrow from men for patterns and time course of infiltration of the skin by
      Y chromosome-bearing lymphocytes using in situ hybridization. Immunophenotypic
      analysis was performed on serial sections. Significant numbers of donor cells
      were first observed by day 13 after bone marrow transplantation (BMT), although a
      few cells were noted at earlier time points. The quantity of donor lymphocytes in
      the dermis correlated with the diagnosis of GVHD. For specimens with grade 1
      features, only rare cells bore the Y chromosome, whereas the majority of
      lymphocytes in grade 2 tissues, whether heavily inflamed or not, contained the Y
      chromosome. These lymphocytes were predominantly CD4+ with fewer CD8+ and CD56+
      cells in the dermis and epidermis. No concentration of a specific subtype in the
      epidermal compartment was observed. These data do not support the observation
      that a cutaneous graft-versus-host reaction (GVHR) is mediated primarily by CD8+
      lymphocytes. Several effector cell populations may mediate a cutaneous GVHR with
      further variation over time and in BMTs between different individuals.

PMID- 9609141
TI  - Sterile neutrophilic folliculitis with perifollicular vasculopathy: a distinctive
      cutaneous reaction pattern reflecting systemic disease.
AB  - The authors prospectively encountered skin biopsies from 20 patients which
      demonstrated a neutrophilic or suppurative and granulomatous folliculitis
      accompanied by a folliculocentric neutrophilic vascular reaction of Sweet's-like
      or leukocytoclastic vasculitis subtypes. While in each case the histomorphology
      raised diagnostic consideration of bacterial folliculitis, patients frequently
      expressed systemic complaints such as arthritis, fever, and malaise, and special
      stains for micro-organisms were negative. Among the clinical presentations were
      folliculitis, vasculitis, acneiform eruptions, vesiculopustular lesions, and
      erythema nodosum-like lesions, with the legs, arms, and upper back being the most
      commonly involved sites. Nineteen patients were found to have specific underlying
      systemic diseases, namely, inflammatory bowel disease, Reiter's disease, Behcet's
      disease, hepatitis B, connective tissue disease including mixed connective tissue
      disease and rheumatoid arthritis, scrofuloderma, and hematologic dyscrasias. The
      other patient had antecedent bacterial sinusitis in the setting of atopy. The
      folliculocentric nature of these lesions may reflect preferential processing of
      antigens through the hair follicle and/or homology between bacterial and
      follicular heat shock proteins in the susceptible host, namely, one who responds
      excessively to exogenous antigenic triggers. Folliculitis with folliculocentric
      vasculopathy may be a clue to underlying systemic disease and/or an
      extracutaneous infection. Certain light microscopic features in concert with the
      clinical presentation may distinguish such cases from conventional infectious
      folliculitis.

PMID- 9609142
TI  - Lichen planoporitis: keratosis lichenoides chronica revisited.
AB  - We report a 70-year-old woman who over a 7-year period developed a widespread
      violaceous, reticulate and striate eruption with a keratotic component in a
      clinical pattern previously described as keratosis lichenoides chronica. Multiple
      biopsies showed a lichenoid reaction centred over the acrosyringium and eccrine
      ducts entering the epidermis. The acrosyringeal ducts were surrounded by an
      epidermis that was associated with saw-tooth acanthosis. The ducts displayed
      hypergranulosis and keratin plugs that extended into the stratum corneum. In the
      upper dermis the eccrine ducts showed squamous metaplasia with liquefaction of
      degeneration of their basal cells as well as apoptotic keratinocytes. The
      subepidermal acrosyringial zone and the eccrine ducts were associated with
      lymphocytic inflammation and fibrosis. These histopathological findings may
      represent the counterpart of lichen planopilaris targeting the eccrine ducts. The
      clinical features defining keratosis lichenoides chronica probably represents a
      heterogeneous group of conditions including this distinctive subset of lichen
      planus which we have termed lichen planoporitis.

PMID- 9609143
TI  - Stimulation of folliculo-sebaceous proliferations by neurofibromas: a report of
      two cases.
AB  - Two unrelated patients, a woman aged 44 and a man aged 56, with a type I
      neurofibromatosis, showed comedo-like formations at the top of some
      neurofibromas. One of them was excised in each case and they were studied
      histopathologically. The comedo-like formation of the first case mimicked the
      epithelial component of a fibrofolliculoma, and that of the second case had the
      structure of a primary late microcomedo and showed also anagen hair
      differentiation in the form of a follicular bulb and papilla. Both events are
      considered to be the result of a stimulation phenomenon and to reflect the
      essential role of the stroma in many cutaneous epithelial hyperplasias,
      hamartomas and possibly in some neoplasms.

PMID- 9609144
TI  - Sebaceous neoplasm with reticulated and cribriform features: a rare variant of
      sebaceoma.
AB  - Troy and Ackerman defined the term sebaceoma (Am J Dermatopathol 1984: 6: 7-13)
      as benign neoplasm of basaloid cells with varying numbers of mature sebocytes.
      Steffen and Ackerman (Neoplasms with sebaceous differentiation. Philadelphia: Lee
      and Febiger, 1994: 401-425) illustrated many examples of sebaceoma, two of which
      had a reticulated and cribriform pattern. We report a case of sebaceoma from the
      scalp of a 52-year-old white female. Histologically, it displayed reticulated and
      cribriform basaloid epithelial islands. This is the third reported case of
      sebaceoma, to our knowledge, with these unusual features.

PMID- 9609145
TI  - What's in a name?

PMID- 9609146
TI  - Malpractice issues in radiology. Teleradiology.

PMID- 9609147
TI  - Disclosure of results of sonographic examinations to patients by sonologists.
AB  - OBJECTIVE: The aim of this study was to assess if patients prefer to talk with a
      sonologist concerning the results of sonographic examinations. MATERIALS AND
      METHODS: The study involved outpatients who underwent diagnostic sonography.
      Technologists offered patients the chance to speak with a sonologist about the
      results of their sonograms. If requested, a sonologist reviewed the results, and
      if the study showed an abnormality, its significance was discussed. No treatment
      recommendations were offered. Patients then filled out a questionnaire. RESULTS:
      Of the 391 outpatients given the choice, 348 (89%) requested a consultation and
      207 of those (60%) returned the completed questionnaire. Of the 207 patients
      completing the questionnaire, 94% preferred receiving the results from the
      sonologist rather than from their referring physician. CONCLUSION: We propose a
      revision of the traditional role of the office-based sonologist to one in which
      he or she will function as a consultant to both the patient and the patient's
      physician.

PMID- 9609148
TI  - "Conventional radiograph," not "plain film".

PMID- 9609149
TI  - Helical body CT: evolution of scanning protocols.

PMID- 9609150
TI  - Helical CT pneumocolon to assess colonic tumors: radiologic-pathologic
      correlation.
AB  - OBJECTIVE: The objective of this study was to determine the accuracy of helical
      CT pneumocolon in the staging of colonic carcinomas. SUBJECTS AND METHODS: Fifty
      two patients (27 men, 25 women; age range, 40-88 years old; mean age, 67 years
      old) with known or strongly suspected colonic disorders underwent CT pneumocolon.
      After bowel cleansing, administration of smooth muscle relaxant, and rectal air
      insufflation, CT pneumocolon was performed with 5-mm collimation, 2.5-mm
      reconstruction interval, and a pitch of 1.5. Two contrast administration
      protocols were used. Twelve patients received 100 ml of i.v. contrast material
      that was injected at 3 ml/sec; scan delay was 45 sec. The other 40 patients
      received 150 ml of contrast material at 5 ml/sec; scan delay was 25 sec. Images
      were prospectively evaluated. All patients had pathologic confirmation: 46
      patients had resections and six patients had endoscopic biopsies. RESULTS:
      Diagnostic images were obtained in 47 of 52 patients. In the 47 patients, there
      were 38 colonic carcinomas (one synchronous), nine diverticular strictures, eight
      polyps, one ischemic stricture, and one normal study. Thirty of 38 carcinomas
      were correctly staged by CT. Sensitivity and specificity for serosal infiltration
      were 100% (35/35 carcinomas) and 33% (one of three carcinomas), respectively;
      sensitivity and specificity for lymph node involvement were 56% (nine of 16
      carcinomas) and 95% (21/22 carcinomas), respectively. Four polyps that were
      smaller than 5 mm in diameter were not revealed by CT. Twelve of 14 benign
      lesions were correctly diagnosed and two were believed to be malignant. No
      malignant lesion was misdiagnosed. CONCLUSION: CT pneumocolon gave an overall
      staging accuracy of 79% in 38 carcinomas.

PMID- 9609151
TI  - Helical CT with only colonic contrast material for diagnosing diverticulitis:
      prospective evaluation of 150 patients.
AB  - OBJECTIVE: We prospectively evaluated a helical CT technique in which contrast
      material is administered only through the colon for the imaging of suspected
      diverticulitis. SUBJECTS AND METHODS: One hundred fifty consecutive patients who
      presented to our emergency department with clinically suspected diverticulitis
      underwent helical abdominal CT after contrast material was administered only
      through the colon. CT findings of diverticulitis included diverticula, muscular
      wall hypertrophy, focal colonic wall thickening, and pericolonic fat stranding.
      CT results were correlated with clinical follow-up (all patients) and with
      pathologic findings (41 patients). RESULTS: A final clinical diagnosis of
      diverticulitis was made in 64 patients (43%), of whom 62 (97%) had CT results
      positive for diverticulitis. Of the 86 patients for whom diverticulitis was
      clinically excluded, all (100%) had CT results that were negative for
      diverticulitis. CT interpretations had a sensitivity of 97%, a specificity of
      100%, a positive predictive value of 100%, a negative predictive value of 98%,
      and an overall accuracy of 99%. Alternative diagnoses were noted on CT in 50
      (58%) of 86 patients who did not have diverticulitis and included 50 (78%) of the
      64 patients in whom an alternative condition other than nonspecific abdominal
      pain was established. CONCLUSION: Helical CT obtained after contrast material
      administered only through the colon is accurate (99%) for confirming or excluding
      clinically suspected diverticulitis and for suggesting alternative conditions
      (78%) when they are present. This CT technique avoids the risks, discomforts, and
      costs of oral and i.v. contrast material administration and allows immediate
      scanning.

PMID- 9609152
TI  - Sonographic appearance of benign and malignant conditions of the colon.
AB  - OBJECTIVE: The objective of this study was to compare the sonographic appearance
      of different abnormalities of the colon to evaluate the role of sonography in
      their differential diagnosis. MATERIALS AND METHODS: We retrospectively reviewed
      videotaped sonographic examinations of 99 patients with proven diagnoses that
      included diverticulitis (n = 35), malignancy (n = 20), Crohn's disease (n = 16),
      pseudomembranous colitis (n = 14), ischemic colitis (n = 9), and ulcerative
      colitis (n = 5). Data were collected with regard to gut features, including the
      site of colonic involvement, associated small-bowel involvement, length of
      diseased segment, stratification, luminal contents, pneumatosis, and diverticula.
      Perigut features evaluated included abnormal fat, abscess, fistula, and ascites.
      RESULTS: On sonography, the following features were statistically significant (p
      < .05). Involvement of the small bowel was more common in patients with Crohn's
      disease than in the remainder of the study population (44% versus 1%). Left-sided
      colonic disease (91% versus 38%), diverticula (91% versus 3%), and perigut
      findings (91% versus 57%), including abnormal fat (83% versus 39%) and abscess
      (34% versus 8%), were features that indicated diverticulitis. Malignant
      conditions were more common in patients with a greater wall thickness (mean, 26.2
      mm versus 10.2 mm), asymmetric involvement (85% versus 39%), loss of
      stratification (85% versus 20%), absence of perigut findings (65% versus 22%),
      and involvement of a short diseased segment (70% versus 16%). Involvement of the
      entire colon (50% versus 2%), luminal contents (64% versus 28%), and ascites (64%
      versus 26%) were features suggesting pseudomembranous colitis. CONCLUSION:
      Although the sonographic appearances of abnormalities of the colon overlap, some
      sonographic features are helpful in the differential diagnosis of colonic
      abnormalities.

PMID- 9609153
TI  - MR imaging of the small bowel using the HASTE sequence.
AB  - OBJECTIVE: To establish the normal MR appearance of small bowel on half-Fourier
      acquisition single-shot turbo spin-echo (HASTE) sequence and to determine the
      ability of HASTE to reveal small-bowel disease. MATERIALS AND METHODS: HASTE
      images in 50 patients without small-bowel disease were reviewed retrospectively
      to determine the normal MR appearance of small bowel. All patients fasted for at
      least 6 hr. The images of 18 patients with proven small-bowel abnormalities that
      were obtained with the HASTE sequence were also reviewed retrospectively by one
      observer unaware of the findings. The ability to characterize small-bowel
      diseases using the HASTE sequence was assessed. RESULTS: In the 50 patients with
      normal small bowel, no fluid was seen in the jejunum and ileum loops in four
      (8%). Fluid was present in less than 25% of small-bowel loops in 20 patients
      (40%), 25-50% of small-bowel loops in 20 patients (40%), and 50-75% of small
      bowel loops in six patients (12%). Equal amounts of fluid were present in the
      jejunum and ileum in 30 patients (60%). More fluid was seen in the jejunum than
      the ileum in 16 patients (32%) and the reverse was true in four patients (8%).
      The mean diameter of the jejunum was 2.1 cm (SD = 0.34 cm) and of the ileum, 1.9
      cm (SD = 0.41 cm). The thickness of the small-bowel wall and valvulae conniventes
      averaged 2 mm. Findings of dilatation of the bowel lumen and increased thickness
      of the bowel wall and valvulae conniventes were identified in 18 patients with
      small-bowel abnormalities. CONCLUSION: The normal and abnormal small bowel can be
      assessed using the HASTE sequence.

PMID- 9609154
TI  - Fast MR imaging and the detection of small-bowel obstruction.
AB  - OBJECTIVE: Our aim was to determine whether fast MR imaging using the half
      Fourier acquisition single-shot turbo spin-echo (HASTE) MR sequence is accurate
      for diagnosis of small-bowel obstruction. MATERIALS AND METHODS: Forty-three
      nonconsecutive patients with suspected small-bowel obstruction were evaluated
      with HASTE MR imaging during a 12-month period. Images were retrospectively
      assessed for the presence, level, and cause of bowel obstruction. Data were
      compared with results of conventional radiography and findings at surgery when
      available. RESULTS: Of the 43 patients imaged, 29 patients had small-bowel
      obstruction revealed by unenhanced or contrast-enhanced radiography or by CT.
      Surgical confirmation was available in 21 patients. Small-bowel obstruction was
      shown by HASTE MR imaging in 26 (90%) of these 29 patients. HASTE MR images
      showed the correct level of obstruction in 19 (73%) of the 26 patients and showed
      the cause of obstruction in 13 (50%) of the 26 patients. CONCLUSION: With a high
      degree of accuracy, HASTE MR imaging can show the presence and level of small
      bowel obstruction.

PMID- 9609155
TI  - Fast MR abdominal imaging using the HASTE sequence.

PMID- 9609156
TI  - A new design of the esophageal Wallstent endoprosthesis resistant to distal
      migration.
AB  - OBJECTIVE: Because plastic-covered metallic stents used in the palliation of
      patients with unresectable esophageal cancer are associated with significant
      rates of migration, particularly when the lower end of the stent projects into
      the gastric fundus, the purpose of this study was to establish whether two new
      prototype designs of the Wallstent esophageal endoprosthesis are prone to
      migration. SUBJECTS AND METHODS: A cylindrical stent and a conical stent were
      studied. Both designs included plastic covering inside the metallic mesh. In
      addition, the conical device incorporated a variation in the braiding angle
      between the upper and lower parts of the endoprosthesis. Ten conical stents and
      eight cylindrical stents were inserted in 18 patients with tumors involving the
      gastroesophageal junction who were followed up with esophagography and endoscopy.
      RESULTS: All insertions of stents were successful. Two cylindrical stents (25%)
      migrated distally. Two conical stents (20%) migrated proximally. One perforation
      occurred that was associated with distal migration of a cylindrical stent.
      CONCLUSION: The frequency of distal migration of cylindrical stents is
      unacceptably high. Conical stents are resistant to distal migration, although
      improvements in design are required to deal with the problem of proximal
      migration.

PMID- 9609157
TI  - Nonendoscopic, fluoroscopically guided gastric biopsy augmenting the double
      contrast upper gastrointestinal examination.

PMID- 9609158
TI  - Lipomas of the pancreas.
AB  - OBJECTIVE: The purpose of this study was to describe the CT findings of
      pancreatic lipomas in four patients. CONCLUSION: In all four cases, the lipoma
      was revealed incidentally on CT scans obtained for other reasons. CT scans were
      diagnostic, showing well-circumscribed masses within the pancreas composed almost
      entirely of fat, with a few scattered vessels or septa or both, which ranged in
      size from 1.4 x 2.0 cm to 4.5 x 5.3 cm in the axial plane. Pancreatic lipomas are
      rare, usually incidental tumors and, as with lipomas found elsewhere in the body,
      conservative management is often indicated.

PMID- 9609159
TI  - Tailgut cyst with malignancy: MR imaging findings.

PMID- 9609160
TI  - Neoplastic pancreaticobiliary duct obstruction: evaluation with breath-hold MR
      cholangiopancreatography.
AB  - OBJECTIVE: The purpose of this study was to investigate the use of breath-hold
      single-shot fast spin-echo MR cholangiopancreatography in neoplastic
      pancreaticobiliary duct obstruction. MATERIALS AND METHODS: Breath-hold MR
      cholangiopancreatography was performed for preoperative examination of 32
      consecutive patients with pathologically confirmed neoplastic obstruction of the
      biliary tract or pancreatic duct using a single-shot fast spin-echo sequence. Two
      observers, unaware of clinical or pathologic findings, independently reviewed the
      MR cholangiopancreatograms to assess level of obstruction and site of underlying
      tumor. Pathologic diagnoses, based on surgical or CT-guided biopsy specimens,
      were pancreatic tumor (n = 12), gallbladder cancer (n = 9), intrahepatic cancer
      (n = 9), and ampullary cancer (n = 2). RESULTS: On the basis of conventional
      cholangiography, CT, and surgical findings, 20 patients had isolated bile duct
      obstruction, 11 patients had combined pancreatic and bile duct obstruction, and
      one patient had isolated pancreatic duct obstruction. Isolated bile duct
      obstruction was classified as lobar (n = 5), hilar (n = 12), or distal (n = 3).
      These levels of obstruction were correctly identified in 27 (84%) and 28 (88%) of
      the 32 cases by the two observers. The site of the underlying tumor was
      identified in 27 (84%) and 29 (91%) cases by the two observers. Good
      interobserver agreement was reached for both level of obstruction (kappa = .70)
      and identification of tumor site (kappa = .75). CONCLUSION: Breath-hold single
      shot fast spin-echo MR cholangiopancreatography is accurate in identifying the
      level of obstruction and the site of underlying tumor in neoplastic
      pancreaticobiliary duct obstruction, with good interobserver agreement.

PMID- 9609161
TI  - Normal Vaterian sphincter complex: evaluation of morphology and contractility
      with dynamic single-shot MR cholangiopancreatography.
AB  - OBJECTIVE: The objective of this study was to assess the usefulness of dynamic
      single-shot MR cholangiopancreatography in the evaluation of the morphology and
      contractility of the normal Vaterian sphincter complex and to assess whether i.v.
      injection of glucagon can improve visualization. SUBJECTS AND METHODS: Sixty
      patients without signs of Vaterian sphincter complex dysfunction were studied. A
      fast single-shot MR imaging sequence was used to obtain 20 consecutive images of
      the Vaterian sphincter complex during successive episodes of breathholding. In
      patients of group A (n = 30), 10 images were obtained before and 10 after i.v.
      administration of a sphincter-relaxing agent (glucagon). In the patients of group
      B (n = 30), no glucagon was administered. The degree of visualization of the
      Vaterian sphincter complex was assessed. RESULTS: Overall, the morphology and
      contractility of the Vaterian sphincter complex was adequately assessed in 57
      patients (95%). However, the number of repetitions required to obtain this result
      varied greatly (mean, seven; range, two to 18). Glucagon had no apparent effect
      on the visibility of the most distal portion of the common bile duct. CONCLUSION:
      Nonvisualization of the most distal portion of the common bile duct on MR
      cholangiopancreatography studies is a normal variant that can simulate disease.
      Obtaining serial breath-hold images using a single-shot technique is helpful to
      avoid diagnostic errors.

PMID- 9609162
TI  - MR imaging during arterial portography for assessment of hepatocellular
      carcinoma: comparison with CT during arterial portography.
AB  - OBJECTIVE: The purpose of this study was to document the usefulness of MR imaging
      during arterial portography (MRAP) versus CT during arterial portography (CTAP)
      in the diagnosis and assessment of hepatocellular carcinoma. SUBJECTS AND
      METHODS: In addition to static T1- and T2-weighted MR imaging, MRAP was performed
      immediately after hepatic angiography through contrast material injection into
      intraarterially placed catheters (superior mesenteric or splenic artery) in 21
      patients with nodular hepatocellular carcinoma. CTAP was performed afterward for
      each patient. The sensitivity and specificity of MRAP for lesion detection and
      the differential diagnosis of hepatocellular carcinoma were compared with the
      sensitivity and specificity of CTAP. RESULTS: MRAP revealed more perfusion
      defects (n = 56) than did CTAP (n = 46). The sensitivity for detection of
      hepatocellular carcinoma was higher for MRAP (94%) than for CTAP (83%); however,
      the difference was not statistically significant (p > .05). More hepatocellular
      nodules with unknown malignant potential were revealed on MRAP (n = 7) than on
      CTAP (n = 2). For the differential diagnosis of perfusion defects commonly
      revealed by both techniques, more benign lesions and pseudolesions (n = 14) were
      shown on MRAP through the combined interpretation with static images than on
      unenhanced and contrast-enhanced CTAP (n = 11). CONCLUSION: Because of its high
      sensitivity and its ability to enable radiologists to differentiate benign from
      malignant conditions, MRAP may have merit compared with CTAP in the assessment of
      hepatocellular carcinoma.

PMID- 9609163
TI  - Accuracy of high-resolution CT in diagnosing lung diseases.
AB  - OBJECTIVE: The purpose of our study was to determine if high-resolution CT
      facilitates the diagnoses of three diseases that cause cystic air spaces in the
      lungs: pulmonary eosinophilic granuloma, pulmonary lymphangiomyomatosis, and
      emphysema. MATERIALS AND METHODS: Retrospective review of high-resolution CT
      findings in patients with pathologically proven pulmonary eosinophilic granuloma
      (n = 10), pulmonary lymphangiomyomatosis (n = 9), and emphysema (n = 10) and five
      control patients without cystic air spaces was conducted by two thoracic
      radiologists unaware of the pathologic diagnosis. After reviewing the scans, the
      radiologists made a diagnosis and indicated their level of confidence in the
      diagnosis on a three-point scale. RESULTS: High-resolution CT allowed the two
      radiologists to be confident of the diagnosis of pulmonary eosinophilic granuloma
      in 84% of CT scans, lymphangiomyomatosis in 79%, and emphysema in 95%. When
      confident, the observers were correct in 100% of the cases. Agreement between
      observers was good for confident diagnoses based on high-resolution CT scans of
      pulmonary eosinophilic granuloma (kappa = .77), lymphangiomyomatosis (kappa =
      .88), and emphysema (kappa = 1). Distribution of cystic changes differed on high
      resolution CT scans for lymphangiomyomatosis and pulmonary eosinophilic
      granuloma. No consistent distribution pattern was observed for emphysema. Lack of
      a perceptible cyst wall was unique to cases of emphysema. All patients with
      lymphangiomyomatosis lacked nodules in the intervening lung parenchyma, whereas
      most patients with pulmonary eosinophilic granuloma had parenchymal nodules.
      CONCLUSION: High-resolution CT can help radiologists reliably diagnose pulmonary
      eosinophilic granuloma, lymphangiomyomatosis, and emphysema.

PMID- 9609164
TI  - Association of small cell lung cancer and the anti-Hu paraneoplastic syndrome:
      radiographic and CT findings.
AB  - OBJECTIVE: The anti-Hu syndrome (bearing the name of the patient in whom the
      antibody was first discovered) is characterized by a paraneoplastic
      encephalomyelitis or sensory neuronopathy and the presence of a specific antibody
      in the serum or CSF and is associated with lung cancer in most patients who have
      the syndrome. The objective of this study was to determine the relative merits of
      chest radiography and CT in the imaging of patients with the anti-Hu syndrome.
      MATERIALS AND METHODS: Chest radiographic and CT findings of 11 patients with
      anti-Hu syndrome were reviewed and correlated with results of bronchoscopy,
      surgery, or autopsy. RESULTS: Ten of the 11 patients had small cell lung cancer;
      in the remaining patient, no cancer was found. Small cell lung cancer was first
      revealed on radiographs in one patient and solely on CT in the remaining nine
      patients with small cell lung cancer. In six of these nine patients, the initial
      CT findings were positive for lung cancer. Tumor was found on follow-up CT in 4-8
      months when initial CT findings were negative. Mediastinal adenopathy was present
      in all 10 cancer patients. Hilar adenopathy was present in four. Parenchymal
      involvement was seen in three of the 10 patients with cancer. In two patients,
      the only CT finding of small cell lung cancer was one mediastinal lymph node of
      10 mm in each patient. CONCLUSION: Chest CT should be recommended for patients
      with anti-Hu syndrome, even when chest radiographic findings are interpreted as
      normal.

PMID- 9609165
TI  - Rounded atelectasis and mesothelioma.
AB  - OBJECTIVE: The purpose of this article is to report the coexistence of rounded
      atelectasis with malignant pleural mesothelioma as revealed by radiography and
      CT. CONCLUSION: Our five cases show the coexistence of rounded atelectasis and
      malignant mesothelioma. If rounded atelectasis is associated with a pleural
      effusion, a pleural mass with or without chest-wall invasion, or thickened pleura
      not adjacent to the rounded atelectasis, malignant mesothelioma should be
      strongly considered.

PMID- 9609166
TI  - Periaortic hematoma on helical CT of the chest: a criterion for predicting blunt
      traumatic aortic rupture.
AB  - OBJECTIVE: The purpose of this study was to evaluate the accuracy of helical CT
      of the chest for predicting blunt traumatic aortic ruptures when periaortic
      hematoma is used as a positive criterion. CONCLUSION: We recommend the use of
      periaortic hematoma as a criterion for predicting traumatic aortic ruptures on CT
      because this criterion is sensitive and can reduce the false-positive rate of CT
      interpretations.

PMID- 9609167
TI  - Computed radiography of the chest in patients with paraesophageal varices:
      diagnostic accuracy and characteristic findings.
AB  - OBJECTIVE: The purpose of our study was to determine the diagnostic accuracy of
      computed radiography of the chest in the detection of paraesophageal varices and
      to describe the characteristic radiographic findings. SUBJECTS AND METHODS: From
      June 1995 through May 1997, in 100 consecutive patients, portal hypertension was
      diagnosed through both clinical and radiologic evidence. Computed radiographs of
      the chest and hepatic helical CT scans of these 100 patients with portal
      hypertension and 20 control subjects were analyzed by two chest radiologists and
      one abdominal radiologist, who were not aware of the results of the other study.
      RESULTS: On CT, paraesophageal varices were seen in 38 (38%) of 100 patients with
      portal hypertension. Overall, the sensitivity, specificity, and accuracy of chest
      computed radiography in the detection of paraesophageal varices were 53% (20/38),
      90% (74/82), and 78% (94/120), respectively. In the patients with paraesophageal
      varices, splenomegaly (29/38, 76%), lateral displacement or obliteration of the
      inferior portion of the azygoesophageal interface (18/38, 47%), obliteration or
      nodularity of the inferior portion of the descending thoracic aorta interface
      (9/38, 24%), lateral displacement of the right inferior paraspinal interface
      (6/38, 16%), lateral displacement of the left inferior paraspinal interface
      (4/38, 11%), and varices in the left inferior pulmonary ligament (1/38, 3%) were
      seen on chest computed radiographs. Paraesophageal varices smaller than the
      diameter of the descending thoracic aorta (usually <2.5 cm) were not detected.
      CONCLUSION: Although chest computed radiography is only moderately sensitive for
      paraesophageal varices, the findings are characteristic when well developed, with
      a limited differential diagnosis. Splenomegaly, whether detected clinically or
      radiographically, eliminates most other diagnostic possibilities.

PMID- 9609168
TI  - Upper-extremity deep vein thrombosis and chronic pulmonary embolism resulting in
      pulmonary artery hypertension.

PMID- 9609169
TI  - Preaortic esophageal veins: CT appearance.
AB  - OBJECTIVE: The purpose of this study was to describe the CT imaging features of
      preaortic esophageal veins in 10 patients with liver cirrhosis. CONCLUSION:
      Preaortic esophageal veins deriving from the paraesophageal varices course
      anterior to the descending aorta and drain into the hemiazygos vein. Preaortic
      esophageal veins are anatomically identical to extrinsic esophageal veins. The
      diameter of the veins we studied ranged from 1 to 8 mm (mean, 3.1 mm). Two
      preaortic esophageal veins were noted in each of two patients.

PMID- 9609170
TI  - Previous breast biopsy for benign disease rarely complicates or alters
      interpretation on screening mammography.
AB  - OBJECTIVE: It has been suggested that breast screening leads to too many biopsies
      for benign disease that permanently scar the breast and confuse the
      interpretation of subsequent mammograms. We undertook retrospective and
      prospective studies to determine how often an excisional biopsy for benign breast
      disease complicates or alters interpretation of screening mammograms. MATERIALS
      AND METHODS: Retrospective review of our screening center database yielded 31,025
      asymptomatic patients who had routine mammographic screening studies between 1993
      and 1996. Of the 58,538 examinations of these patients, 53,510 were of patients
      who had no history of breast biopsy and 5028 were of patients who had a history
      of breast biopsy for benign disease. Recall rates were compared between the two
      groups. In the prospective study, radiologists reviewed the mammograms of 1997
      consecutive patients presenting to the screening center, 173 of whom reported a
      prior breast biopsy for benign disease. The radiologist interpreting the images
      determined how often evidence of the biopsy site was apparent on the mammogram
      and how often such changes necessitated additional imaging. RESULTS: In the
      retrospective study, 3296 (6%) of the 53,510 studies done in patients who did not
      have a biopsy for benign disease and 360 (7%) of the 5028 studies done in women
      who had a biopsy for benign disease led to additional imaging. Eight recalls for
      further imaging (0.16%) among the 5028 studies in women with a prior biopsy for
      benign disease were related to the biopsy site. In the prospective study, 24
      (14%) of the 173 women who had a biopsy for benign disease had mammographic
      evidence of the biopsy site. Nine (5%) of the 173 women who had previously had a
      biopsy for benign disease and 86 (5%) of the 1824 patients without a prior biopsy
      were recalled for additional imaging. No women were recalled because a previous
      breast biopsy for benign disease led to confusion or diagnostic concern.
      CONCLUSION: Changes in patients' breasts due to previous excisional biopsies for
      benign breast disease rarely pose a diagnostic dilemma in the interpretation of
      routine screening mammograms.

PMID- 9609171
TI  - Ductal carcinoma in situ of the breast: mammographic-pathologic correlation.

PMID- 9609172
TI  - Anatomy and clinical significance of the horizontal cleft in the infrapatellar
      fat pad of the knee: MR imaging.
AB  - OBJECTIVE: The purpose of this study was to determine the prevalence and nature
      of a horizontal cleft in the posterior aspect of Hoffa's infrapatellar fat pad
      and to show pathologic processes involving this cleft. MATERIALS AND METHODS:
      Fifty consecutive MR imaging examinations of the knee were evaluated for the
      presence and appearance of a cleft in the infrapatellar fat pad. Examples of
      abnormalities involving the cleft were collected from additional MR studies. MR
      imaging, gross dissection, and histologic examination of a cadaveric knee were
      also performed to evaluate the anatomy and histology of the cleft. RESULTS: The
      cleft in the infrapatellar fat pad was revealed on MR imaging in 45 of 50 knees
      and had a variable shape, either linear (82%), pipe-shaped (7%), or globular
      shaped (11%). Joint effusion or anterior cruciate ligament tear did not affect
      the appearance of the cleft. The cleft was located anterior to the distal
      insertion of the anterior cruciate ligament on the tibia. At gross dissection of
      the cadaveric knee, the roof of the cleft was formed by the ligamentum mucosum
      (infrapatellar plica), and the cleft was lined with synovium. The prospective
      evaluation of additional MR imaging examinations of the knee revealed pathologic
      entities of the cleft such as ganglion cysts, loose bodies, nodular synovitis,
      and amyloid. CONCLUSION: A horizontal cleft located in the posterior aspect of
      the infrapatellar fat pad is a common and normal MR imaging finding with a
      prevalence of 90%. The horizontal cleft is lined with synovium and its roof is
      formed by the ligamentum mucosum (infrapatellar plica). This cleft communicates
      with the knee joint. A distended cleft can form a prominent recess mimicking
      pathologic processes; conversely, disorders can arise in the cleft.

PMID- 9609173
TI  - Metallosis after total knee replacement.

PMID- 9609174
TI  - Tendinopathy and rupture of the tendon of the long head of the biceps brachii
      muscle: evaluation with MR arthrography.
AB  - OBJECTIVE: The purpose of this study was to assess the diagnostic role of MR
      arthrography in patients with tendinopathy or rupture of the long biceps tendon.
      MATERIALS AND METHODS: MR arthrograms of 42 consecutive patients with
      arthroscopic or surgical confirmation of diagnosis (16 normal biceps tendons, 19
      with tendinopathy, and seven with ruptures) were analyzed independently by two
      radiologists. Visibility of the biceps tendon, caliber changes, contour
      irregularities, and signal intensities were assessed separately in the
      parasagittal and axial planes. In addition, the two radiologists made an overall
      evaluation of abnormalities of the biceps tendon using both MR imaging planes.
      RESULTS: The most reliable MR findings for tendinopathy were caliber changes
      (sensitivity was 59% for observer 1 and 82% for observer 2; specificity was 88%
      and 64%, respectively) and signal abnormalities (sensitivity, 77% and 88%,
      respectively; specificity, 75% and 43%, respectively) in the parasagittal plane.
      Absence of visualization of the tendon in the parasagittal plane was a reliable
      sign for rupture (sensitivity, 86% and 86%, respectively; specificity, 94% and
      87%, respectively). The overall sensitivity for detecting abnormalities
      (tendinopathy or rupture) was 92% for observer 1 and 89% for observer 2.
      Specificity was 56% and 81%, respectively. CONCLUSION: MR findings of
      tendinopathy and rupture of the biceps tendon are subtle. However, the
      combination of several MR criteria in two imaging planes makes a reasonably
      accurate diagnosis possible. The biceps tendon should not only be assessed in the
      bicipital sulcus on axial images but also on parasagittal images.

PMID- 9609175
TI  - The linear intravertebral vacuum: a sign of benign vertebral collapse.
AB  - OBJECTIVE: We describe 11 patients with radiographically visible linear
      intravertebral vacuums to increase awareness of this benign finding that is
      diagnostic of ischemic necrosis of the vertebral body (Kummell's disease).
      MATERIALS AND METHODS: We retrospectively reviewed the radiologic and clinical
      histories of 11 patients seen at our institution between 1991 and 1997 in whom
      the linear intravertebral vacuum phenomenon had been diagnosed. Imaging included
      plain radiographs in all patients, CT scans in three, bone scintigrams in three,
      and MR images in three. RESULTS: Twelve linear intravertebral vacuums associated
      with vertebral compression deformities were visible in 11 patients from T8 to L2,
      four at T12, and four at L1. Of the 12 linear intravertebral vacuums, seven (58%)
      were seen by the initial interpreting radiologist. The mean age of these patients
      was 76.6 years. The female:male ratio was 10:1. During the period of analysis,
      two patients were known to have malignancy, one with metastasis to the spine but
      not to the affected vertebral body. One patient, who underwent equivocal MR
      imaging for malignancy, later underwent bone biopsy, which showed no neoplasm
      within the collapsed vertebra. Of the remaining nine patients, one was undergoing
      chronic corticosteroid therapy and another had a history of radiation therapy to
      the spine. Seven of the 11 patients had histories of falling, prompting
      radiographs of the spine. All 11 patients were radiographically osteopenic.
      Ultimately, none of the patients had clinical evidence of neoplasm or infection
      involving the affected vertebral body. CONCLUSION: Recognition of the near
      certain benign significance of a linear intravertebral gas collection revealed by
      radiography may prevent unnecessary imaging or biopsy in a patient with a
      suggestive vertebral compression deformity.

PMID- 9609176
TI  - Osteochondromalike parosteal osteosarcoma: a report of six cases of a new entity.
AB  - OBJECTIVE: Our purpose was to describe a rare juxtacortical bone sarcoma with
      deceptively benign, osteochondromalike histologic characteristics. We present
      criteria by which this low-grade malignant neoplasm can be distinguished from
      other benign and malignant surface lesions of bone with particular emphasis on
      the imaging features. MATERIALS AND METHODS: Six cases of a low-grade,
      chondroossifying parosteal sarcoma of bone were reviewed. Patients included four
      males and two females 11 months to 66 years old. Histologic findings from initial
      tumors and from recurrent tumors were reviewed. Two musculoskeletal radiologists
      analyzed the imaging studies, which included plain films, CT scans, MR images,
      and a bone scan. RESULTS: Histologically, the lesions were characterized by a
      thin layer of proliferating, periosteally derived spindle cells overlying a thin,
      low-grade malignant cartilage cap that underwent calcification,
      neovascularization, and conversion into benign bone and marrow fat. These lesions
      were unique in that the malignant elements were only at their periphery. All six
      cases were initially misdiagnosed as benign lesions on pathologic evaluation. In
      each patient, imaging revealed a "pasted-on" ossified surface lesion with an
      intact underlying cortex and no medullary involvement. In three cases, recurrent
      tumors had histologic appearances consistent with conventional parosteal
      osteosarcoma. Dedifferentiation, metastases, and death occurred in one of these
      three cases. CONCLUSION: To our knowledge, this surface lesion of bone has not
      been specifically described. Whether this tumor constitutes a distinct entity or
      is a specialized variant of parosteal osteosarcoma is unclear. Precise radiologic
      pathologic correlation is essential for appropriate diagnosis and management.

PMID- 9609177
TI  - Ganglion cysts of the knee: articular communication revealed by delayed
      radiography and CT after arthrography.
AB  - OBJECTIVE: The diagnosis of ganglion cysts of articular origin may sometimes be
      uncertain when communication with the joint is not evident. Because we have
      observed that opacification of ganglion cysts revealed by arthrography can be
      significantly delayed, the purpose of this study was to determine retrospectively
      in 20 cases the time delay needed to show with arthrography a communication
      between the articular cavity and ganglion cysts of the knee. CONCLUSION:
      Arthrographic evidence of a communication between the articular cavity of the
      knee and communicating ganglion cysts requires delayed radiography performed at
      least 1 hr after intraarticular injection of contrast material. The best results
      are obtained with additional CT performed 1-2 hr after injection.

PMID- 9609178
TI  - Unilateral hypertrophic osteoarthropathy associated with aortobifemoral graft
      infection.

PMID- 9609179
TI  - Interventional radiology case conference: the University of Texas Medical Branch.
      Percutaneous management of pyogenic spondylodiskitis.

PMID- 9609181
TI  - Possible causes of inconclusive results on CT-guided thoracic and abdominal core
      biopsies.
AB  - OBJECTIVE: We sought to determine possible technical causes of inconclusive
      results on CT-guided core biopsies of lesions suggestive of malignancy and to
      determine the frequency with which such lesions are eventually found to be
      malignant. MATERIALS AND METHODS: We retrospectively reviewed 116 consecutive CT
      guided thoracic and abdominal core biopsies performed with a 20-gauge automatic
      biopsy system. Biopsy results were conclusive (n = 94) if pathology confirmed
      malignancy and inconclusive (n = 22) if pathology results were negative for
      malignancy or were nondiagnostic. Lesion volume, location, number of cores, and
      biopsy technique (paraxial or coaxial) were compared for the conclusive and
      inconclusive biopsy results. Malignancy within the group of inconclusive biopsy
      results was determined from a second biopsy, radiographic follow-up, or surgery.
      RESULTS: Regression analysis identified only the biopsy method as a significant
      factor affecting biopsy outcome: The paraxial method was more likely to yield a
      conclusive result than the coaxial method (p < .002). For the two biopsy methods,
      lesions had similar volumes, locations, and numbers of cores obtained. For single
      core biopsies, both methods were equivalent. However, if two or more cores were
      obtained, a conclusive result was achieved in more than 90% of biopsies with the
      paraxial method versus 65% for the coaxial method. On follow-up, results of 14
      (64%) of 22 inconclusive biopsies were malignant, indicating an overall false
      negative rate of 12%. CONCLUSION: CT-guided core biopsy performed with 20-gauge
      automatic biopsy systems and the paraxial method will yield conclusive results
      significantly more often than the coaxial method. In the event of inconclusive
      results, malignancy will exist often enough to warrant follow-up.

PMID- 9609180
TI  - Interactive MR imaging-guided biopsy and aspiration with a modified clinical C
      arm system.
AB  - OBJECTIVE: This investigation was performed to test the hypotheses that
      interactive guidance of MR image acquisition during needle-directed procedures
      using a clinical 0.2-T C-arm open MR imaging system integrated with a frameless
      optically linked stereotaxy system is feasible, and that procedure times can be
      sufficiently short to be well tolerated by the patient. SUBJECTS AND METHODS: One
      hundred six MR-guided procedures were performed in 86 patients (ranging in age
      from 5 months to 88 years) using a clinical C-arm imaging system supplemented
      with an in-room RF-shielded liquid crystal display monitor, a frameless
      stereotaxy system, rapid gradient-echo sequences for needle guidance, and MR
      compatible monitoring and surgical lighting equipment. We performed 50 biopsies
      and aspirations of the head and neck in 37 patients, 23 biopsies of
      musculoskeletal lesions in 22 patients, 16 biopsies of abdominal sites in 10
      patients, six biopsies of the thoracolumbar spine or sacrum in six patients, and
      11 shoulder joint injections for MR arthrography in 11 patients, in addition to
      38 MR arthrographic injections on the same imaging system described in a previous
      report. Tissue sampling included fine-needle aspiration (n = 90) and cutting
      needle core biopsy (n = 41). Thirty-five patients underwent both procedures.
      Procedures were evaluated for success of needle placement, procedure time, and
      complications. RESULTS: Needle placement was successful in all cases, and no
      complications occurred. Tissue was sufficient for pathologic diagnosis for all
      but eight patients. Passes per patient averaged 2.1. For fine-needle aspiration,
      instrument time averaged 7 min 42 sec per pass, cutting needle core biopsy
      averaged 6 min 24 sec, and shoulder injection averaged 8 min. CONCLUSION: MR
      imaging guidance for needle procedures on a clinical 0.2-T C-arm system with
      supplemental interventional accessories is feasible, with relatively rapid needle
      placement.

PMID- 9609182
TI  - Peripherally inserted central venous catheters: factors affecting patient
      satisfaction.
AB  - OBJECTIVE: We studied factors that affect satisfaction of patients who have
      undergone placement of peripherally inserted central venous catheters (PICCs) by
      interventional radiologists and patients' willingness to undergo placement of
      future PICCs. SUBJECTS AND METHODS: This longitudinal prospective consecutive
      cohort study included 85 patients referred for PICC placement. A record was made
      of catheter type, time taken for placement, patient age, and possible
      complications. Follow-up was obtained by telephone interview to determine the
      effect of site of placement in the arm, residence time of catheter, additional
      complications, and interference with activities of daily living on patient
      willingness to undergo future PICC placement at the same site. Logistic
      regression analysis was used to determine factors statistically predictive of
      patient willingness to undergo placement of future PICCs. RESULTS: Patients
      having PICCs placed above the elbow were more often satisfied (55 of 61
      respondents) with catheter location than patients having placements at the elbow
      (three of 17 respondents). Patient willingness to undergo future PICC placement
      was strongly related to catheter location (p < .0001) and interference with
      activities of daily living (p < .0001). Catheter type, residence time, time taken
      for the placement, age, and complications were not associated with patient
      willingness to undergo future PICC placement. CONCLUSION: PICC placement above
      the elbow is more acceptable to patients than placement at the elbow. PICC
      placement above the elbow and patients' perception of less interference by the
      PICC with activities of daily living are positively related to patient
      willingness to undergo future PICC placement.

PMID- 9609183
TI  - Sonographically guided placement of peripherally inserted central venous
      catheters: review of 355 procedures.
AB  - OBJECTIVE: This paper reviews our experience using sonographic guidance in the
      insertion of peripherally inserted central venous catheters (PICCs). SUBJECTS AND
      METHODS: Three hundred fifty-five PICCs were placed in 262 patients, 19-92 years
      old, over a 24-month period using sonographic guidance for the initial venous
      cannulation. RESULTS: The average number of punctures was 1.2, with an average
      procedure time of 21 min. Our overall success rate to achieve the initial venous
      access was 99%. I.v. contrast material was used in only 2% of the cases, after
      successful initial venous access with sonographic guidance alone, to allow
      demonstration of anatomic variations or lesions that interfered with the
      completion of the procedure. Two immediate minor complications occurred. A high
      margin of safety was provided by avoiding the use of iodinated contrast medium
      and by visualizing the artery and its anatomic relation to the vein before and
      during needle placement. CONCLUSION: Sonographic guidance yielded superior three
      dimensional localization of the selected vein and its precise anatomic
      relationship to the artery. Our experience has led us to conclude that
      sonographically guided placement of PICCs is a fast, safe, efficient, and
      inexpensive technique and should be the preferred method for PICC placement,
      especially in patients with no clinically identifiable peripheral vein.

PMID- 9609184
TI  - Central venous access: low internal jugular vein approach using imaging guidance.
AB  - OBJECTIVE: The use and safety of a low internal jugular vein cannulation
      technique for central venous access was prospectively evaluated. CONCLUSION: The
      inferior internal jugular vein provides a safe and direct route to the superior
      vena cava and right atrium for central venous access. Use of an internal jugular
      vein cannulation site at the base of the neck avoids kinking of tunneled and
      untunneled catheters.

PMID- 9609185
TI  - Helical CT of traumatic arterial injuries.

PMID- 9609186
TI  - The yield of CT of children who have complicated pneumonia and noncontributory
      chest radiography.
AB  - OBJECTIVE: Our purpose was to investigate the usefulness of CT in evaluating
      children who do not respond appropriately to treatment for pneumonia, when chest
      radiography is noncontributory. MATERIALS AND METHODS: Fifty-six contrast
      enhanced CT scans were compared with radiographs obtained on the same day in
      children with complicated pneumonia. CT scans were evaluated for clinically
      significant findings that were not revealed by radiography: lung parenchymal
      complications (cavitary necrosis, abscess, decreased enhancement, bronchopleural
      fistula, or cavity suspected on radiography but not seen on CT), pleural
      complications (loculation, malpositioned chest tube), inaccurate estimation of
      cause of chest opacity on radiography (pleural versus parenchymal), bronchial
      obstruction, or pericardial effusion. RESULTS: One hundred ten CT findings, not
      revealed by radiography, were seen on 56 CT scans (2.0 per CT scan): parenchymal
      complications (n = 40), pleural complications (n = 37), inaccurate estimation of
      cause of chest opacity on radiography (n = 20), pericardial effusion (n = 13).
      All CT scans showed at least one significant finding (100% yield) not seen on
      radiography. CONCLUSION: In the evaluation of children with complicated
      pneumonia, CT often reveals clinically significant findings not apparent on
      radiography.

PMID- 9609187
TI  - Gadolinium-enhanced MR imaging of pediatric patients after reduction of
      dysplastic hips: assessment of femoral head position, factors impeding reduction,
      and femoral head ischemia.
AB  - OBJECTIVE: We describe gadolinium-enhanced MR imaging of position and vascular
      enhancement of the femoral head in pediatric patients who have undergone
      reduction of hip dislocation. SUBJECTS AND METHODS: Within 24 hr of hip reduction
      and spica casting, we performed 25 gadolinium-enhanced MR studies in 18 infants
      and young children (15 girls, three boys) with 23 dysplastic hips. All but two
      patients underwent closed reductions. We evaluated intraoperative arthrograms for
      obstacles to reduction and subsequent radiographs for avascular necrosis.
      RESULTS: MR images showed that all femoral heads were in their respective
      acetabula, but several structures interfered with concentric reduction. Obstacles
      to reduction included a pulvinar (n = 16), infolding of the capsule (n = 9),
      interposition of the labrum (n = 2), and a hypertrophied ligamentum teres and
      transverse ligament (n = 2). All 50 femoral heads showed enhancement: 35
      normally, 10 homogeneously but less than on the contralateral femoral head or the
      ipsilateral greater trochanter, and five with areas of focally decreased
      enhancement. Hips that showed decreased enhancement had undergone greater degrees
      of abduction (r = .38, p < .01). CONCLUSION: Gadolinium-enhanced MR imaging can
      reveal abnormalities of hip position and proximal femoral epiphyseal and physeal
      vascularity that can occur after hip reduction. Abnormalities of enhancement were
      more frequent in patients who had greater femoral abduction. The effect of
      decreased epiphyseal vascular enhancement is still uncertain.

PMID- 9609189
TI  - A pattern approach to the differential diagnosis of intramedullary spinal cord
      lesions on MR imaging.

PMID- 9609188
TI  - MR imaging of thoracic tumors in pediatric patients.

PMID- 9609190
TI  - Calcified filum terminale paraganglioma causing superficial siderosis.

PMID- 9609191
TI  - Hydrogen peroxide poisoning causing brain infarction: neuroimaging findings.
AB  - OBJECTIVE: We describe the CT and MR imaging findings of the brain in patients
      who inadvertently poisoned themselves with concentrated hydrogen peroxide. Thirty
      five percent hydrogen peroxide is commercially available as an oxidant and
      disinfectant. This solution is currently sold and promoted in health food stores
      in the United States as a means of "improving oxygenation" in people with
      coronary artery disease and other health problems. CONCLUSION: Our findings show
      the high toxicity of concentrated hydrogen peroxide. CNS damage and death are
      likely consequences after ingestion of this agent.

PMID- 9609192
TI  - Improving CT angiography of the carotid artery using the "right" arm.

PMID- 9609193
TI  - Limbic encephalitis: comparison of FDG PET and MR imaging findings.

PMID- 9609195
TI  - The postpneumonectomy syndrome.

PMID- 9609194
TI  - MR features of the lacrimal gland in Sjogren's syndrome.
AB  - OBJECTIVE: Our purpose was to investigate the MR features of the lacrimal glands
      in patients with Sjogren's syndrome. SUBJECTS AND METHODS: Using MR imaging, we
      examined 58 lacrimal glands in 29 women with Sjogren's syndrome and 150 lacrimal
      glands in 75 female control subjects. The patients ranged in age from 21 to 76
      years, and the control subjects ranged in age from 0 to 78 years. We analyzed the
      thicknesses and internal signal intensity patterns of the lacrimal glands and
      compared the results with lacrimal flow rates using Schirmer's test. RESULTS: On
      the basis of the profile of normal age-related decreases in lacrimal gland
      thickness that we obtained from our control subjects, we categorized the lacrimal
      glands in the patients with Sjogren's syndrome as hypertrophic (7.8 +/- 0.8 mm),
      normal-sized (4.8 +/- 1.2 mm), or atrophic (2.4 +/- 0.5 mm). The patients had
      slower lacrimal flow rates than did the control subjects. Atrophic lacrimal
      glands had slower lacrimal flow rates (1.8 +/- 1.2 mm/5 min) than did normal
      sized (5.2 +/- 2.8 mm/5 min) and hypertrophic (4.3 +/- 2.6 mm/5 min) glands.
      Normal-sized lacrimal glands with homogeneous MR features had faster lacrimal
      flow rates (7.6 +/- 2.2 mm/5 min) than did normal-sized glands with heterogeneous
      MR features (4.0 +/- 2.4 mm/5 min). Fat suppression studies showed that fat
      deposition was accelerated in the lacrimal glands of patients with Sjogren's
      syndrome. CONCLUSION: These results suggest that change in size associated with
      accelerated fat deposition may be the characteristic MR feature of lacrimal
      glands affected by Sjogren's syndrome. Thus, MR imaging could be a useful tool
      for assessment of the extent of lacrimal gland involvement in patients with
      Sjogren's syndrome.

PMID- 9609196
TI  - MR arthrography.

PMID- 9609197
TI  - The use of helical CT angiography for examination of living renal donors.

PMID- 9609198
TI  - A plea and pledge against excessive use of abbreviations in medical literature
      (APPEAL)

PMID- 9609199
TI  - The status quo is not tenable.

PMID- 9609200
TI  - Adhesion-related abdominal wall varices: demonstration by color Doppler
      sonography.

PMID- 9609201
TI  - Agenesis of the parotid gland: association with ipsilateral accessory parotid
      tissue.

PMID- 9609202
TI  - Radiologic findings in chronic esophagitis dissecans.

PMID- 9609203
TI  - Multifocal primary colonic lymphoma in a patient with posttransplantation
      lymphoproliferative disease: CT findings.

PMID- 9609204
TI  - Osteoporosis: preventive strategies.
AB  - In the United States alone, osteoporosis affects over 20 million women. The cost
      of treating the complications of osteoporosis exceeds 10 billion dollars. Half of
      those who sustain a hip fracture never return to their former life style. In
      addition, there is a major increase in mortality within the first year of a hip
      fracture. These facts dictate an urgent need to address issues relevant to the
      prevention of osteoporosis. Only by preventing bone loss will it be possible to
      meet the challenge of dealing effectively with this major public health problem.
      There are three major components of an effective preventive strategy. The first
      is to ensure that optimal peak bone mass is achieved during childhood,
      adolescence and early adulthood. Although much of peak bone mass is determined by
      genetic influence, there are other factors of importance over which one has
      control. These include adequate dietary calcium intake, good nutrition, exercise
      and hormone sufficiency. The second aspect to prevention is maintaining bone mass
      that has been acquired. Bone maintenance requires adequate calcium intake and
      exercise as well as avoiding tobacco and excessive alcohol. Certain diseases
      (i.e., hyperthyroidism) and medications (i.e., steroids, anticonvulsants) will
      tend to erode the repositories of bone at any time in life. The third aspect to
      prevention is counteracting the process of age-related bone loss that occurs
      after 40-45 years of age. In women, the menopause markedly accelerates bone loss.
      Measures to ensure that bone loss is minimized during the middle years and beyond
      include adequate nutrition (vitamin D and calcium) and hormone sufficiency. For
      women, hormone replacement therapy is a gold standard of therapy because it
      arrests bone loss associated with the menopause. For women who cannot or will not
      take estrogen, newer, effective approaches, such as estrogen analogues and the
      nonhormonal bisphosphonates, are available. With this three-phased approach,
      requiring constant attention to bone health over one's entire life, the risk of
      developing osteoporosis and its complications can be minimized.

PMID- 9609205
TI  - Women's health: not for women only.
AB  - Because most medical investigation traditionally has been restricted to men, many
      of our models of normal human physiology and of the pathophysiology of disease
      are skewed. The current interest in women's health has led us to concentrate on
      the differences between men and women; indeed, a survey of already published data
      reveals that there are significant variations in the normal function of virtually
      all the systems in the body. Furthermore, each of the sexes experiences disease
      differently in many important respects: coronary artery disease is a well
      understood example of how gender determines the pathobiology of illness. As our
      understanding of the impact of gender on the mechanism of disease expands, our
      treatment of illness will become more focused and accurate. Sex-specific
      prescribing may well become the norm as the science of gender-specific medicine
      expands.

PMID- 9609206
TI  - Injectable depot medroxyprogesterone acetate contraception: an update for U.S.
      clinicians.
AB  - Injectable contraceptions appeal to women who value the efficacy, convenience,
      and safety provided by this reversible birth control option. Since FDA approval
      for contraceptive use in 1992, depot medroxyprogesterone acetate (DMPA)--already
      used by millions of women worldwide--has been used by several million U.S. women.
      Although women using this 3-month progestin-only injectable often experience
      irregular bleeding and spotting (initially), long-term DMPA use typically results
      in amenorrhea. Many users, including adolescents, choose DMPA because of its
      convenience--nearly 100% contraceptive effectiveness is achieved with 4
      injections per year. Because DMPA does not contain estrogen, it represents an
      appropriate contraceptive choice for postpartum or lactating women, as well as
      those whose medical status precludes use of contraceptive doses of estrogen. Some
      examples include: women over age 35 who smoke, those with increased
      thromboembolism risk, women with cardiovascular or liver disease, as well as
      women with complex migraines. Although fertility resumes on the average 10 months
      following the last injection, suppression of ovulation occasionally persists for
      as long as 22 months. Consequently, DMPA is not an appropriate choice for women
      who may wish to conceive within the next two years. Since the use of DMPA lowers
      ovarian estradiol production, reversible loss of bone mineral density (BMD) may
      occur. Studies currently in progress may clarify DMPA's long-term impact, if any,
      on BMD. Therapeutic uses of DMPA include treatment of: dysmenorrhea, menorrhagia
      (including that associated with fibroid uterine tumors), endometriosis,
      endometrial hyperplasia, ovulatory pain, pain associated with ovarian adhesive
      disease, premenstrual dysphoria and perimenopausal symptoms.

PMID- 9609207
TI  - An update on coronary heart disease in women.
AB  - Coronary heart disease is the leading cause of mortality for adult women in the
      United States, accounting for the death of nearly 250,000 women each year. Once
      coronary disease becomes clinically evident, it causes prominent morbidity and
      disability in women, particularly among older women. Women are more likely to die
      from an episode of myocardial infarction than are men, and first-year mortality
      following myocardial infarction is comparably greater for women. Similarly, women
      do not fare as well as men following myocardial revascularization procedures,
      having a greater mortality from coronary artery bypass graft surgery, less graft
      patency, less symptomatic relief, and more reoperation within the initial
      postoperative 5 years. Despite initial favorable outcomes from percutaneous
      transluminal coronary angioplasty, women have less long-term symptomatic relief
      and decreased long-term survival, the latter, however, predominantly related to
      their older age. The increased case fatality rates and greater morbidity of women
      following both myocardial infarction and myocardial revascularization procedures
      underscore the need for preventive interventions for women across their life
      span. Dramatic strides have been made in recent years, based on the recognition
      of the importance of coronary heart disease as a health problem for women. There
      is an increased emphasis on coronary preventive strategies, improvement in the
      prompt evaluation of chest pain syndromes, and increase in the performance of
      myocardial revascularization when appropriate; research is also under way to
      assess risk interventions unique to women.

PMID- 9609208
TI  - Androgens and women's health.
AB  - Androgenic disorders are those conditions in women characterized by excessive
      androgen action. They are the most common endocrinopathy of women, affecting from
      10% to 20%. Signs are: persistent acne, hirsutism and androgenic alopecia, which
      is the female equivalent of male pattern baldness. A subgroup, those
      traditionally labeled as having polycystic ovary syndrome (PCOS), additionally
      have anovulation, as well as menstrual abnormalities and, often, obesity.
      Although women with androgenic disorders usually present themselves for help with
      the skin or menstrual changes, there are other important implications regarding
      their health. Women with PCOS have varying degrees of insulin resistance, and an
      increased incidence of Type II diabetes mellitus, as well as unfavorable lipid
      patterns. The presence of these risk factors is suggested by upper segment
      obesity, darkening of the skin, and the other skin changes that make up
      acanthosis nigricans. Diagnosis involves measurement of circulating androgens (of
      which free testosterone is most important), together with prolactin and FSH when
      menstrual dysfunction is present. Many women with androgenic skin changes have
      normal serum androgen levels, suggesting increased end organ sensitivity to
      androgens. Others have hyperandrogenism (of ovarian or adrenal origin). Treatment
      is usually successful in controlling acne, reducing hirsutism and stabilizing, or
      partially reversing, androgenic alopecia. Pharmacological approaches involve
      suppressing androgen levels, for example, the use of an appropriate oral
      contraceptive, or antagonizing androgen action with several medications that have
      this activity. Unfortunately, most women with androgenic disorders are frustrated
      in their efforts to obtain medical help. Understanding androgenic disorders will
      enable the physician to significantly help the majority of women with these
      conditions.

PMID- 9609209
TI  - Use of combined estrogen-androgen preparations in the postmenopause: evidence
      from clinical studies.
AB  - This article reviews the effects, on clinical symptoms, such as energy level and
      aspects of sexual functioning in postmenopausal women, of adding testosterone to
      an estrogen replacement regimen. The efficacy of combined estrogen-androgen
      preparations on bone density and lipoprotein lipid metabolism is also reviewed.
      Clinical recommendations for use of combined therapy are described with respect
      to specific symptoms.

PMID- 9609210
TI  - Migraine: diagnosis and rational treatment.
AB  - When patients present with severe, incapacitating headaches, they are often
      concerned with whether or not they are suffering from a severe illness, or even a
      brain tumor. The next concern is the relief of the incapacitating pain. In
      adults, primary headache disorders account for approximately 80% of the headaches
      experienced, compared with 20% for secondary headache disorders. Migraine, one of
      the most common disabling headaches, afflicts more than 18 million women and 5
      million men with severe, incapacitating pain. Determining which headache patient
      requires a detailed evaluation can be facilitated by the use of the International
      Headache Society criteria, a thorough history, and a complete physical
      examination. The management of headaches, specifically migraines, encompasses
      both pharmacologic and nonpharmacologic strategies, requiring the integration of
      new medications into our established treatment profiles. Selecting appropriate
      pharmacologic therapy also requires the recognition of comorbid conditions
      associated with headache. Physicians and allied health care professionals can
      improve the quality of life and headache patients by instituting and coordinating
      comprehensive therapeutic approaches.

PMID- 9609211
TI  - Obesity: a never-ending cycle?
AB  - Obesity is the number one public health concern in the United States, affecting
      over one-third of women. Minorities are at highest risk, with nearly 50% of
      African-American and Mexican-American women obese. Obesity significantly
      increases risk for mortality and morbidity in women, including several
      gynecological and reproductive disorders and infertility. Obesity, with the
      resultant hyperinsulinemia and hyperandrogenemia, negatively affects normal
      menstrual function and fertility. In addition, maternal adiposity may increase
      risk in offspring through perinatal mechanisms, resulting in a never-ending cycle
      of obesity. Data suggest that modest weight losses of about 10% of initial weight
      are effective in improving hormonal profiles, menstrual regularity, ovulation,
      and pregnancy rates. Available treatments include life-style modification
      programs, with a focus on eating a healthful diet and increasing physical
      activity, plus adjunctive pharmacotherapies.

PMID- 9609212
TI  - Use of tretinoin in female health practice.
AB  - Tretinoin (all trans-retinoic acid) is extensively used in the treatment of acne
      as Retin-A; of photoaging as Renova; and in the treatment of striae distensae.
      The indications, rationale, and clinical observations are discussed in detail so
      that these may be instituted in the practice of female health.

PMID- 9609213
TI  - Postmenopausal sexual functioning: a case study.
AB  - Most men and women remain sexually active into mid-life and beyond. However,
      sexual functioning in peri- and postmenopausal women, and their partners, is
      widely variable. Somatic symptoms, psychological issues, partner's physical,
      psychological, and relationship status are all important to one's perceived
      quality of life, and may greatly affect sexuality. These wide-ranging influences
      complicate assessment, diagnosis, and subsequent management of sexual problems. A
      number of factors influence sexual functioning in menopausal women. There are age
      related changes that are unrelated to menopause, which include changes in drive,
      body image, and general health status. Beliefs about menopause and sexuality
      impact sexual functioning in women. Changes in relationship status and the
      physical health of a partner may also influence sexuality. Physiologic changes,
      directly related to menopausal hormone changes, often impact sexual functioning,
      both directly and indirectly. Health care providers can play an important role in
      treating sexual problems and enhancing sexuality in aging patients. Effective
      evaluation will result in accurately determining the source(s) of an individual's
      or a couple's sexual dysfunction. Treatment may include the following: basic
      education about sexuality and sexual functioning, normalizing sexual activity in
      aging adults, medical management of symptoms or problems that are interfering
      with sexual desire or activity (such as HRT for vaginal atrophy or in reduction
      of hot flashes), referral for treatment of the partner's physical or
      psychological problem, and/or sex therapy to treat a sexual dysfunction or to
      manage a chronic physical problem that requires a change in a person's or
      couple's typical sexual repertoire. This paper includes a detailed case history
      of a couple to illustrate the concepts mentioned above.

PMID- 9609214
TI  - Francois-Henri Duckert, 1922-1998.

PMID- 9609215
TI  - European Working Group on Clinical Cell Analysis: Consensus protocol for the flow
      cytometric characterisation of platelet function.

PMID- 9609216
TI  - Comparison of a once daily with a twice daily subcutaneous low molecular weight
      heparin regimen in the treatment of deep vein thrombosis. FRAXODI group.
AB  - BACKGROUND: Clinical trials have been performed to compare with standard heparin
      a once or a twice daily regimen of low-molecular-weight heparin but no direct
      comparison has been done between these two low-molecular-weight heparin regimens
      in terms of efficacy and safety with a long-term clinical evaluation. METHODS:
      Patients with proximal deep vein thrombosis, confirmed by venography were
      randomly assigned to either nadroparin (10,250 AXa IU/ml) twice daily or
      nadroparin (20,500 AXa IU/ml) once daily for at least 5 days. Regimens were
      adjusted to bodyweight. Oral anticoagulants were started on day 1 or 2 and
      continued for 3 months. Patients were followed up for 3 months. The composite
      outcome of venous thromboembolism and death possibly related to pulmonary
      embolism was the primary measure of efficacy. Major bleeding was the principal
      measure of safety. The study was designed to show equivalence between the two
      regimens. RESULTS: Recurrent thromboembolic events or death possibly related to
      pulmonary embolism were reported in 13 patients in the once daily group (4.1%)
      and in 24 patients of the twice daily group (7.2%): (absolute difference 3.1% in
      favor of the once daily regimen; 95% confidence interval -6.6%, +0.5%). Major
      bleeding episodes during nadroparin treatment occurred in 4 (1.3%) and 4 patients
      (1.2%) in the once and twice daily groups, respectively. CONCLUSIONS: A
      nadroparin regimen of one injection per day is at least as effective and safe as
      the same total daily dose divided over two injections for the treatment of acute
      deep vein thrombosis.

PMID- 9609217
TI  - Low molecular weight heparin decreases proximal and distal deep venous thrombosis
      following total knee arthroplasty. A meta-analysis of randomized trials.
AB  - OBJECTIVES: To assess the efficacy and safety of low molecular weight heparin
      (LMWH) as deep venous thrombosis (DVT) prophylaxis following total knee
      arthroplasty. DATA SOURCES: Medline 1986 to June 1997, Embase, and manufacturers
      were used to identify randomized controlled trials. REVIEW METHODS: Trials
      included were randomized studies of LMWH with routine radiological screening for
      DVT. Placebo or active controls were included. Two reviewers independently
      screened trials for inclusion, and assessed their quality. Pooled relative risk
      estimates of DVT and proximal DVT rates were calculated using a DerSimonian and
      Laird random effects model. Sensitivity of the results to the type of control
      used and the quality of the trial was assessed. RESULTS: The relative risk of DVT
      for a patient given LMWH is 0.73 (95% CI 0.66 to 0.80) when compared with
      patients treated with adjusted dose heparin or warfarin controls. The relative
      risk for proximal DVT is 0.58 (95% CI 0.38 to 0.90). The relative risk of
      pulmonary emboli in the LMWH group was 0.55 (95% C.I. 0.20 to 1.57). No excess of
      bleeding was recorded in the LMWH group. CONCLUSIONS: Low molecular weight
      heparin is more efficacious than either adjusted dose heparin or adjusted dose
      warfarin, when used to prevent DVT and proximal DVT following total knee
      arthroplasty.

PMID- 9609218
TI  - The methylenetetrahydrofolate reductase TT677 genotype is associated with venous
      thrombosis independently of the coexistence of the FV Leiden and the prothrombin
      A20210 mutation.
AB  - A polymorphism, C-->T677, in the methylenetetrahydrofolate reductase (MTHFR) gene
      has been identified as a cause of mild hyperhomocysteinemia, a risk factor for
      venous thrombosis. We have investigated the frequency of the TT genotype in 277
      consecutive patients with confirmed deep venous thrombosis and 431 healthy
      subjects. The TT MTHFR genotype was more frequent in patients than in controls
      (25.6% vs. 18.1%; p = 0.016). The risk of thrombosis among carriers of this
      genotype was significantly increased [odds ratio: 1.6 (95% CI: 1.1-2.3)]. The
      estimated risk associated with the TT genotype was 2.0 (95% CI: 1.3-3.1) in
      subjects with (n = 122), and 1.3 (95% CI: 0.8-2.0) in those without (n = 155)
      predisposing (hereditary, acquired or circumstantial) risk factors for venous
      thrombosis. Factor V Leiden and prothrombin G-->A20210 are known risk factors for
      venous thrombosis. After stratification for FV Leiden and prothrombin A20210
      mutations, a significant association was also observed. After adjustment for sex,
      FV Leiden and prothrombin A20210 mutation, the estimated risk of venous
      thrombosis among carriers of the TT MTHFR genotype was 1.7 (95% CI: 1.2-2.6). The
      TT MTHFR genotype is independently associated with venous thrombosis, mainly
      among individuals with a high risk profile.

PMID- 9609219
TI  - Factor V Leiden is not a risk factor for arterial vascular disease in the
      elderly: results from the Cardiovascular Health Study.
AB  - Coagulation factor V Leiden is a risk marker for venous thrombosis. For arterial
      thrombosis no large study to date has included population-based elderly patients.
      The Cardiovascular Health Study is a longitudinal study of 5,201 men and women
      over age 65. With 3.4-year follow-up, we studied 373 incident cases of myocardial
      infarction (MI), angina, stroke. or transient ischemic attack (TIA), and 482
      controls. The odds ratios for each event with heterozygous factor V Leiden were:
      MI, 0.46 (95% CI 0.17 to 1.25); angina, 1.0 (95% CI 0.45 to 2.23); stroke, 0.77
      (95% CI 0.35 to 1.70): TIA, 1.33 (95% CI 0.5 to 3.55); any outcome, 0.83 (95% CI
      0.48 to 1.44). Adjustment for cardiovascular risk factors did not change
      relationships. In older adults factor V Leiden is not a risk factor for future
      arterial thrombosis.

PMID- 9609220
TI  - Platelet count and survival in patients with colorectal cancer--a preliminary
      study.
AB  - In a previous report we found an inverse correlation between pre-operative
      platelet count (PlC) levels and the risk of post-operative pulmonary embolism in
      patients undergoing hip surgery. In the present study, we prospectively evaluated
      the prognostic significance of pre-operative PlC levels on survival in 180
      consecutive patients undergoing surgery for colorectal cancer. Other major
      clinicopathological parameters studied were age, gender, Dukes' stage, duration
      of surgery, pre-operative haemoglobin levels and transfusion requirements. There
      were no significant differences in mean pre-operative PlC levels according to
      tumor stage. Thirty-three patients (18%) died during follow-up (3-23 months,
      median: 13 months). Univariate analysis (Kaplan-Meier estimates) showed that
      advanced tumor stage (p < 0.001), duration of surgery (p < 0.05) and a high pre
      operative PlC level (p < 0.001) were significantly associated to a poor survival.
      The multivariate Cox analysis revealed that tumor stage (RR:5.734; 95%C.I.: 2.644
      12.44), a high pre-operative PlC level (RR: 2.467; 95%C.I.: 1.117-5.452), and to
      a lesser extent the patients' age remained independent prognostic variables for
      mortality. The findings of this preliminary study may be of interest from the
      point of view of pathogenesis, but also clinically, since they might be used in
      the decision as to which patients or groups of patients should receive more
      aggressive therapeutic intervention.

PMID- 9609221
TI  - Increased plasma levels of free tissue factor pathway inhibitor in patients with
      Graves' disease.
AB  - Tissue factor pathway inhibitor (TFPI) is present in a free-form and in
      lipoprotein-associated forms in plasma. In this study, the plasma concentrations
      of total TFPI (tTFPI) and free-form TFPI (fTFPI) were measured in 25 patients
      with Graves' disease and 25 age-matched healthy subjects, and the relationship
      between thyroid state and plasma TFPI was examined. Plasma concentrations
      (median) of tTFPI and fTFPI in Graves' patients who were hyperthyroid were
      significantly increased compared with Graves' patients who were euthyroid (152
      ng/ml versus 124 ng/ml, p < 0.01 and 41.3 ng/ml versus 20.2 ng/ml, p < 0.0001,
      respectively), and control subjects (152 ng/ml versus 96 ng/ml, p < 0.0001 and
      41.3 ng/ml versus 18.7 ng/ml, p < 0.0001, respectively). There was no significant
      difference in plasma fTFPI concentrations between the euthyroid group and the
      control group. Plasma fTFPI concentrations correlated closely with thyroid
      hormone (T3) levels in the patients (r = 0.559, p < 0.005). Serial measurement of
      individual patients revealed that plasma concentrations of fTFPI and tTFPI were
      significantly decreased, reaching normal control values upon attainment of
      euthyroidism. In conclusion, the close correlation between plasma fTFPI and serum
      thyroid hormone levels suggests that thyroid hormones might influence the
      synthesis or metabolism of TFPI on the surface of endothelial cells in patients
      with Graves' disease. This is the first report concerning high concentrations of
      plasma tTFPI in patients with hyperthyroidism.

PMID- 9609222
TI  - Fcgamma receptor IIA H/R131 polymorphism in patients with antiphospholipid
      antibodies.
AB  - A role for Fcgamma receptor in the pathophysiology of thrombosis in APS has been
      hypothesized. The polymorphism of this receptor, FcgammaRIIA H/R131, is
      associated with the binding affinity for human IgG2 (i.e. FcgammaRIIA-H131
      isoform has a higher affinity than FcgammaRIIA-R131). Since anti-beta2
      glycoprotein I antibodies (anti beta2GPI), which play a major pathogenic role in
      APS, show IgG2 dominant distribution, we investigated the prevalence of receptor
      isoforms in patients with antiphospholipid antibodies (aPL) by a PCR-RFLP method.
      We studied 100 Caucasian patients with aPL (57 primary APS, 32 secondary APS to
      SLE and 11 other diseases with aPL) and 41 healthy controls. H131/H131, H131/R131
      and R131/R131 genotypes were found in 21 (21%), 50 (50%) and 29 (29%) in the
      patient group, and 9 (22%), 23 (56%) and 9 (22%) in control group, respectively.
      Thus there was no statistically significant difference in the prevalence of each
      genotype in these groups. None of the clinical manifestations of primary APS
      (arterial/venous thrombosis, recurrent pregnancy loss and thrombocytopenia) was
      significantly correlated with any FcgammaRIIA genotype. In conclusion,
      FcgammaRIIA polymorphism did not correlate with the manifestations of APS, and
      FcgammaRIIA genotype is not a genetic marker of APS.

PMID- 9609224
TI  - Prophylactic use of factor VIII: an economic evaluation.
AB  - BACKGROUND: Since the introduction of exogenous factor VIII therapy, several
      studies have explored the clinical benefits of prophylactic use of factor VIII.
      Little research, though, has focused on the economic aspects of this regimen. We
      conducted a cost analysis using data from the Orthopedic Outcomes Study, a
      prospective, cross-national study of the clinical outcomes associated with
      different patterns of factor VIII utilization to examine the health care costs
      incurred and expenditures averted in patients receiving on-demand versus
      prophylactic use of factor VIII in hemophilia. METHODS AND ANALYSIS: 831 patients
      with severe hemophilia aged 1 to 31 years, from 19 centers around the world were
      included in the cost analysis. Patients were categorized into three groups
      according to the number of weeks during the study years in which they received
      prophylactic regimens of factor VIII. For each subject, we estimated the costs of
      hospitalization, surgery, days lost from school or work, and factor VIII
      utilization. Costs were then stratified by age and by joint score to assess
      confounding, and a multivariate model developed to determine the relationship
      between use of factor VIII prophylaxis and total costs, while controlling for
      potential confounders. RESULTS: Patients who received factor VIII episodically
      incurred substantially greater disability-related costs (days lost from school or
      work, days hospitalized due to hemophilia, surgery) than patients who received
      factor VIII prophylactically for some or all of the study period. For all
      treatment regimens, most disability-related costs were accounted for by
      hospitalization for hemophilia-related conditions. The cost of factor VIII itself
      was substantial in all treatment categories but was highest among patients who
      received year-round prophylaxis, exceeding the savings resulting from reduced
      disability and other health care expenditures. CONCLUSIONS: Reductions in non
      factor health care costs and disability associated with prophylactic use of
      factor VIII in hemophilia were substantial and helped somewhat to offset the much
      higher costs of this regimen. For certain subgroups, frequent episodic treatment
      may be more expensive than full-time prophylaxis. However, because of the very
      high cost of year-round prophylactic use of factor VIII, total health care
      expenditures were highest among patients receiving this therapeutic regimen.
      However, because prophylaxis clearly offers important clinical benefits, this
      approach may be warranted on medical rather than economic grounds.

PMID- 9609223
TI  - Failure of thrombolytic therapy in patients with myocardial infarction is
      associated with high plasma levels of factor VII antigen.
AB  - Thrombolytic therapy in acute myocardial infarction fails to re-establish
      coronary blood flow in a significant number of patients. One reason for this may
      be haemostatic imbalance. We investigated whether coagulation factor VII antigen
      (FVIIag), fibrinogen and protein C were related to reperfusion. Plasma from 45
      patients was drawn before treatment and reperfusion assessed by means of
      continuous, on-line, vector-ECG analysis. Among the 17 patients with no
      reperfusion, FVIIag levels were significantly higher than among the 28 with signs
      of reperfusion (560 vs. 410 microg/l median, p = 0.006). Protein C levels where
      higher in the group with successful reperfusion (1.10 vs. 1.01 U/ml median, p =
      0.03), whereas no difference was seen in fibrinogen levels. The findings were not
      influenced by plasma-triglycerides, body-mass index, age or time between onset of
      chest pain and thrombolytic therapy. The results suggest that FVII is of
      importance for the formation as well as resolution of coronary clots.

PMID- 9609225
TI  - A 20.7 kb deletion within the factor VIII gene associated with LINE-1 element
      insertion.
AB  - Large deletions within the factor VIII gene account for approximately 5% of the
      mutations causing haemophilia A. The characterization of such mutations can
      provide insights into the molecular mechanisms of these and other deletions in
      man. We have analyzed a 20.7 kb deletion spanning exons 15 to 20 within the
      factor VIII gene in a patient with severe haemophilia A. Long range PCR was used
      to investigate the extent of the deletion and to provide a template for
      sequencing across the deletion breakpoint. A 38-base insertion homologous to the
      3' region of a LINE-1 (L1) element was detected at the breakpoint of the
      deletion. Normal sequence at the 5' breakpoint in intron 14 was homologous to an
      L1 flanking region and normal sequence at the 3' breakpoint in intron 20 was
      homologous to an adjacent sequence within the same L1 flanking region. A
      molecular mechanism for the deletion involving retrotransposition of a
      readthrough product of an L1 element plus its 3' flanking region is suggested.

PMID- 9609226
TI  - Partial reconstitution of factor VIII activity from a mild Crm+ hemophilia A
      patient by replacement of the defective A2 domain.
AB  - We further characterised the abnormal factor VIII molecule (factor VIII Leiden)
      of a Crm+, mild hemophilia A patient with a factor VIII activity of 0.18 IU/ml
      and a factor VIII antigen of 0.95 IU/ml. Mutation analysis of the coding region,
      promoter and 3' untranslated region of the factor VIII gene revealed the presence
      of a C to T substitution at codon 527. This nucleotide change predicts the
      replacement of an arginine to tryptophan in the A2 domain close to a suggested
      binding site for factor IXa. Since a previous study of this mutant factor VIII
      protein suggested that this protein had a reduced affinity for factor IXa,
      position 527 in the protein might be involved in the interaction with factor IXa.
      In this study we gathered evidence for our hypothesis that the Arg to Trp
      mutation at position 527 is the cause of the reduced activity of factor VIII
      Leiden. Replacement of the mutated A2 domain by wild type A2 domain partially
      corrected the defect. Factor VIII from normal and factor VIII Leiden plasma was
      concentrated by cryoprecipitation, activated with thrombin and incubated with
      excess wild type A2 domain. Competition with excess isolated human A2 domain
      resulted in a partial reconstitution of the factor VIIa activity of thrombin
      treated factor VIII Leiden. This supports the hypothesis that the mutation in the
      A2 domain is the cause of the reduced factor VIII activity.

PMID- 9609227
TI  - Factor V Leiden (G1691A), the prothrombin 3'-untranslated region variant
      (G20210A) and thermolabile methylenetetrahydrofolate reductase (C677T): a single
      genetic test genotypes all three loci--determination of frequencies in the S.
      Wales population of the UK.
AB  - Simultaneous genetic diagnosis of factor V (FV) Leiden (G1691A), the prothrombin
      variant (G20210A) and the thermolabile methylenetetrahydrofolate reductase
      (MTHFR) variant (C677T) has been achieved using multiplex heteroduplex analysis.
      All three loci are amplified in a single polymerase chain reaction (PCR)
      containing test DNA and three heteroduplex generators, respectively detecting the
      three nucleotide substitutions. After PCR, the products are analysed directly
      without further manipulation and the resulting heteroduplex profiles permit
      straightforward interpretation of the respective genotypes. The multiplex test
      has been used to assess the prevalence and allele frequency of each of the three
      nucleotide substitutions in 300 individuals (150 males and 150 females) from the
      local (S. Wales) population. A prevalence of 8% and an allele frequency of 0.040
      +/- 0.015 (95% confidence interval) was obtained for FV Leiden; the prothrombin
      variant showed a prevalence of 1% and an allele frequency of 0.007 +/- 0.006 (95%
      confidence interval); the MTHFR mutation showed a prevalence of 60% and an allele
      frequency of 0.377 +/- 0.039 (95% confidence interval). This method is applicable
      to investigation of large cohorts of patients with arterial or venous thrombotic
      disease.

PMID- 9609228
TI  - Monoclonal antibodies against beta-2-glycoprotein I: use as reference material
      for lupus anticoagulant tests.
AB  - The laboratory diagnosis of lupus anticoagulants (LA) remains difficult despite
      internationally accepted guidelines for its detection. Several interlaboratory
      surveys have shown poor agreement between laboratories. Further standardization
      of LA testing will to a large extent depend on better insights on the mechanisms
      by which LA affect phospholipid-dependent coagulation assays as well as on the
      availability of well characterized and internationally accepted reference
      materials and control specimens. We recently raised a series of murine monoclonal
      antibodies against human beta2GPI (anti-beta2GPI moabs), a phospholipid-binding
      protein directly involved in the interaction between certain lupus anticoagulants
      and phospholipids. In this study we report on the use of LA positive anti
      beta2GPI moabs as easy to handle reference and control material. The relative LA
      responsiveness of various phospholipid-dependent clotting assays was determined
      on plasmas spiked with such moabs and compared well with that determined on LA
      positive plasma samples. Plasmas spiked with LA positive anti-beta2GPI moabs were
      also used as control specimens to study the interlaboratory precision of LA
      testing. With these control specimens, low interassay coefficients of variation
      were obtained. Our results indicate that LA positive anti-beta2GPI moabs have
      potential for the production of control specimens that could be made available to
      routine hemostasis laboratories to assess intra-laboratory precision of LA
      testing and to manufacturers to control batch-to-batch variability of their
      reagents.

PMID- 9609229
TI  - Cytokine gene expression in human LPS- and IFNgamma-stimulated mononuclear cells
      is inhibited by heparin.
AB  - In addition to its well-understood anticoagulant activity, heparin is known to
      modulate a variety of biological functions including immunologic responses. In
      order to investigate whether heparin influences the humoral immunity by
      interacting with cellular elements and affecting gene expression in blood
      circulating cells. we studied the effect of heparin on IL-1beta, IL-6 and
      TNFalpha mRNAs in human lipopolysaccharide-(LPS)- or interferon-gamma(IFN-gamma)
      stimulated mononuclear cells. The study of mRNA was carried out by an initial PCR
      screening followed by a Northern blot quantitative analysis. Heparin (0.5 U/ml)
      turned out to inhibit all three cytokine gene expressions. The mRNA decrease was
      37 +/- 6% for IL-1beta, 53 +/- 3% for IL-6 and 47 +/- 4% for TNFalpha with LPS
      stimulus. No differences could be observed in the inhibitory effect of heparin on
      IFNgamma-stimulated cells. This effect of heparin was confirmed in a subset of
      experiments performed on purified monocytes. These results suggest an important
      immunosuppressive effect of heparin on cell-mediated immune responses.

PMID- 9609230
TI  - Antibodies against fibrinogen in pregnant women, in post delivery women and in
      the newborns.
AB  - Pregnancy and delivery have measurable effects on haemostatic and immunological
      changes. Degradation of fibrinogen induces significant structural and
      conformational modulation and leads to the progressive loss of antigenic sites
      present on the parent molecule but also exposes some new sites. These neoantigens
      may be recognized by the immune system and may be elicited by the autologous host
      manifested by the production of autoantibodies. Therefore in the present study,
      in pregnant and post delivery women and in the newborns, levels of antibodies
      against fibrinogen, fibrin(ogen) degradation products (FDP) and fibrin
      degradation products (D-dimer) were examined. Enzyme immunoassay (ELISA) was used
      to detect and quantitate autoantibodies against fibrinogen (class G
      immunoglobulin) in human sera. In all sera there were found varying
      concentrations of autoantibodies and their levels were significantly higher in
      all pregnant women in comparison with non-pregnant ones. Significantly higher
      levels were found in Rh immunized and clinically complicated pregnancies. The
      level of autoantibodies, coagulation and fibrinolytic system components were
      higher in post delivery women than in normal pregnant women. Also antibodies to
      fibrinogen were studied in cord serum of newborns in different terms of delivery.
      The low levels of antibodies in all newborns raise questions of possible foetal
      maternal immunologic interactions. Positive correlation between mothers and
      newborns was demonstrated after delivery at gestational age from 34th to 41st
      week, and negative in 42nd and more week. There were no significant differences
      in antibody level among the newborns delivered by the same mothers. It was found
      that autoantibodies bind selectively to the fibrinogen and fibrinogen fragments
      X, Y and D. These autoantibodies may represent a new interface between the
      coagulation and the immune systems which may be significant in controlling the
      pathologic activities of the cleavage fragments.

PMID- 9609231
TI  - Intra- and interindividual variability of hemostatic factors and traditional
      cardiovascular risk factors in a three-year follow-up.
AB  - Elucidation of the key role of thrombosis in cardiovascular disease events has
      arisen considerable interest in hemostatic factors and in the repeatability of
      their determinations. Data on long-term repeatability has, however, remained
      scanty. We examined twice 208 men and 265 women in North Karelia, eastern
      Finland. The baseline examination was a part of the FINRISK 1992 Hemostasis Study
      and the age-range of participants was between 45-64 years. The re-examination
      took place three years later in 1995. Both surveys followed the same protocol and
      were carried out during the same season. Spearman rank correlation coefficients
      between 1992 and 1995 measurements of fibrinogen, factor VII coagulant activity
      (FVII:C), factor VII antigen (FVII:Ag), and plasminogen were among men 0.72,
      0.77, 0.46 and 0.56, respectively. For total cholesterol, HDL-cholesterol,
      triglycerides and diastolic blood pressure the corresponding coefficients were
      0.74, 0.83, 0.66, and 0.54. In women, the coefficient of fibrinogen was lower
      than in men, 0.62, otherwise the results were similar. Of men belonging to the
      highest quarter of fibrinogen, FVII:C, FVII:Ag and plasminogen in 1992, 65%, 60%,
      53% and 60% belonged to the highest quarter of respective distributions also in
      1995. In women, the corresponding proportions were 64%, 65%, 46% and 58%. The
      modest repeatability of FVII:Ag and plasminogen was mainly due to the high
      intraindividual variability. However, in comparisons of plasma levels between two
      groups, relatively small sample sizes seemed to give adequate statistical power
      to detect possible differences in FVII:Ag and plasminogen. In conclusion, the
      long-term repeatability of fibrinogen and FVII:C is similar to that of
      triglycerides and even better than that of diastolic blood pressure, but somewhat
      lower than the repeatability of total cholesterol. FVII:Ag and plasminogen did
      not have very good repeatability and more than one measurement of them should be
      considered if they are used as predictors of cardiovascular disease in
      prospective studies.

PMID- 9609232
TI  - The 4G/5G sequence polymorphism in the promoter of plasminogen activator
      inhibitor-1 (PAI-1) gene: relationship to plasma PAI-1 level in venous
      thromboembolism.
AB  - Impaired fibrinolysis due to increased plasminogen activator inhibitor-1 (PAI-1)
      is observed in up to 40% of patients with venous thromboembolism and might be
      causally related to the disease. There is evidence that genetic variations in the
      promoter of the PAI-1 gene and metabolic factors contribute to increased plasma
      PAI-1 levels. A single nucleotide insertion/deletion (4G/5G) polymorphism in the
      promoter region of the PAI-1 gene and metabolic factors were studied in 158
      unrelated patients below the age of 61 years (43 +/- 11 years, mean +/- standard
      deviation) with history of objectively confirmed venous thromboembolism and in
      145 apparently healthy controls. Patients had on average two times higher PAI
      activity (11.9 vs. 6.1 IU/ml) and by 40% higher PAI-1 antigen (14.8 vs. 10.7
      ng/ml) than healthy controls, and also higher body mass index, lipid levels,
      fasting glucose and insulin. Patients differed significantly from healthy
      controls neither in the frequency of the 4G and 5G alleles (0.57/0.43 in patients
      and 0.52/0.48 in controls) nor in the distribution of the 4G/5G genotypes.
      Possession of the 4G/4G or the 4G/5G genotype did not increase relative risk for
      venous thromboembolic disease and the distribution of the 4G/5G genotypes was
      neither associated with recurrent nor with spontaneous disease. In patients
      association between the 4G/5G genotypes and PAI activity (adjusted for body mass
      index, triglyceride and glucose level) was observed, with the highest PAI
      activity values in the 4G/4G genotype (14.6 IU/ml), intermediate in the 4G/5G
      genotype (13.3 IU/ml) and the lowest in the 5G/5G genotype (5.2 IU/ml, all values
      means). Association between PAI activity and triglyceride level was the strongest
      in the 4G/4G genotype (correlation coefficient r = 0.47, p < 0.01) and the
      weakest in the 5G/5G genotype (r = -0.04, not significant). In conclusion, the
      present case-control study shows an association between the 4G/5G polymorphism in
      the promoter of the PAI-1 gene and plasma PAI-1 levels in patients with venous
      thromboembolism. Similar distribution of the 4G/5G genotypes in patients and
      healthy controls suggests that this genetic variation by itself is not a major
      risk factor for venous thromboembolism.

PMID- 9609233
TI  - Distribution of tissue plasminogen activator insertion/deletion polymorphism in
      myocardial infarction and control subjects.
AB  - An insertion (I)/deletion (D) polymorphism in the tissue plasminogen activator
      (TPA) gene locus has recently been reported to be associated with the risk of
      myocardial infarction (MI) with increased risk in II/ID subjects compared with DD
      subjects. To investigate this further, we analysed 529 acute MI cases and 525
      population-based control subjects recruited in two centers (Leicester and
      Sheffield, UK). We found no difference between cases and controls in TPA I/D
      allele frequencies (cases I = 0.574, controls I = 0.582, p = 0.74) or genotype
      distribution (cases II 33%, ID 48%, DD 19%; controls II 34%, ID 49%, DD 17%, p =
      0.88). Compared with the DD genotype, the age, sex and centre adjusted odds
      ratios for MI for II genotype was 0.95 (95% confidence interval, 0.64-1.40, p =
      0.85) and that for ID genotype was 0.89 (0.62-1.27, p = 0.56). There was no
      significant effect modification by smoking status, body mass index or cholesterol
      level. There was no difference in the reported frequency of positive family
      history of coronary heart disease or mean age at MI in the different genotype
      groups. We conclude that in our populations the TPA I/D polymorphism is not a
      major independent risk factor for myocardial infarction.

PMID- 9609234
TI  - Functional analysis of the amino- and carboxyl-termini of streptokinase.
AB  - Streptokinase (SK) is a 414 amino acid bacterial protein that activates human
      plasminogen. Streptokinase fragments derived from the central portion of the
      protein bind plasminogen, but are inactive, indicating that the amino- and/or
      carboxyl-termini are required for normal plasminogen activator activity. To
      better define the function of the N- and C-termini of SK we generated and
      characterized 21 N-terminal and 20 C-terminal deletion mutants. All mutants
      lacking > or = 18 N-terminal or > or = 51 C-terminal amino acids exhibited
      markedly reduced plasminogen activator activity, while mutants lacking < or = 12
      N-terminal or < or = 40 C-terminal residues were fully active. The decrease in SK
      activity with N-terminal deletion appeared to result not from loss of plasminogen
      binding capacity, but rather from increased susceptibility of deletion mutants to
      degradation by plasmin. Point mutations at positions 13 (SK V13D) or 20 (SK V20D)
      produced functional abnormalities similar to those observed in N-terminal
      deletion mutants, with SK V13D exhibiting delayed amidolytic activity and SK V20D
      exhibiting only 1% plasminogen activator activity and marked sensitivity to
      degradation by plasmin. C-terminal deletion mutants lacking > or = 51 amino acids
      also bound plasminogen, but did not induce significant amidolytic activity in
      plasminogen or activator activity in plasmin. Prevention of cleavage at position
      59 of SK had no effect on plasminogen activator activity, suggesting that the
      rapid hydrolysis of this bond that occurs after SK-plasminogen complex formation
      is not required for normal function of the N-terminus. These results suggest that
      residues within or near positions 13-20 of SK are important determinants of its
      capacity to generate amidolytic activity and are a critical determinant of the
      stability of SK, while residues within or near position 364-374 are required for
      generating amidolytic activity and for conferring plasminogen activator activity
      to plasmin(ogen). These results also suggest that SK fragments significantly
      smaller than SK 13-374 are unlikely to be effective thrombolytic agents.

PMID- 9609235
TI  - Preparation of a novel streptokinase mutant with improved stability.
AB  - The novel mutant streptokinase, SK-K59E, can activate human plasminogen as
      efficiently as the purified commercially available streptokinase. Several peptide
      bonds including Lys59-Ser60 in native streptokinase were hydrolyzed in reaction
      with plasmin and peptides of small molecular masses were generated. The
      plasminogen activator activity of native streptokinase in reaction with human
      plasmin declined to 25% of the original activity in a 120-min incubation. On the
      other hand, the NH2-terminal peptide of SK-K59E remained intact in reaction with
      plasmin and the activator activity of streptokinase decreased to 75% of the
      original activity in 120 min. The major degraded peptide fragments of native
      streptokinase in reaction with plasmin had molecular masses of 36 and 30 kDa.
      However, two major peptide fragments of 42 and 34 kDa were observed in the
      reaction of SK-K59E with human plasmin. The 42 kDa peptide fragment, which
      contained NH2-terminal of streptokinase, could activate human plasminogen as
      efficiently as the native streptokinase. SK-K59E can induce greater degree of
      caseinolysis and fibrinolysis than the native streptokinase. In conclusion, the
      results demonstrate that the prevention of cleavage at Lys59 of streptokinase
      prolongs the half-life of streptokinase in complex with plasmin and that the NH2
      terminal of streptokinase (Ile1-Lys59) plays an important role in maintaining its
      stability.

PMID- 9609236
TI  - Adhesion of ADP-activated platelets to intact endothelium under stagnation point
      flow in vitro is mediated by the integrin alphaIIbeta3.
AB  - As we demonstrated earlier, platelets adhere to intact endothelium provided they
      are activated and convectively transported against the endothelial surface. To
      identify the platelet receptors involved we superfused cultured endothelium with
      activated platelet rich plasma (PRP) by means of the Stagnation Point Flow
      Adhesio- Aggregometer while blocking various platelet receptors. Inhibition was
      performed with the tetrapeptide RGDS, the non-peptide Ro-43-8857, or a monoclonal
      antibody directed against integrin alphaIIbeta3. Platelet deposition was video
      recorded and quantified by image analysis. Infusion of RGDS or Ro-43-8857 into
      ADP-stimulated PRP completely prevented adhesion as well as subsequent
      aggregation. Interrupting the inhibitor infusion while ADP stimulation persisted,
      prompted adhesion and aggregation, demonstrating the reversibility of the
      inhibition. Platelet adhesion was irreversibly blocked by preincubation of the
      PRP with the moab against alphaIIbeta3. Its specific binding was confirmed by
      immunoelectron microscopy. Our results suggest that platelet adhesion to intact
      endothelium is mediated via platelet integrin alphaIIbeta3.

PMID- 9609237
TI  - Detection of platelets activated during acetylcholine-induced coronary vasospasm.
AB  - Although platelet activation may play a role in coronary artery spasm, platelets
      activated following coronary vasospasm have not been clinically detected. We
      performed flow cytometric analysis of activation-dependent granular proteins,
      CD62P (P-selectin), CD63, PAC-1 (activated glycoprotein [GP] IIb/IIIa) and
      thrombospondin on the platelet plasma membrane in patients who exhibited
      acetylcholine-induced coronary vasospasm and compared findings with those in
      control patients without vasospasm. We simultaneously investigated the plasma
      levels of thrombin anti-thrombin III complex (TAT), plasmin alpha2-plasmin
      inhibitor complex (PIC), and thrombomodulin. In patients with vasospasm, the
      expression of CD62P, CD63 and PAC-1 on the platelet membrane surface increased in
      coronary sinus blood samples following coronary vasospasm, although the
      expression in aortic samples did not change. The TAT level also increased in the
      coronary sinus after vasospasm. Platelets might be activated by coronary
      vasospasm within the coronary circulation. The platelet activation process may be
      modulated by thrombin generation.

PMID- 9609238
TI  - Stimulation by G protein betagamma subunits of phospholipase C beta isoforms in
      human platelets.
AB  - Different phospholipase C (PLC) isoforms were located in human platelet cytosol
      and membranes. PLCgamma2 and PLCbeta3b were mainly located in the cytosol and
      PLCbeta2 and PLCbeta3a were in both cytosol and membranes by using specific
      antibodies against PLC isozymes (Banno Y, Nakashima S, Ohzawa M, Nozawa Y. J Biol
      Chem 1996; 271: 14989-94). Three PLC fractions activated by G protein betagamma
      subunits were purified from human platelet cytosol and membrane fractions. Two
      PLC fractions from membranes were identified as PLCbeta2 and PLCbeta3a, and one
      from cytosol was PLCbeta3b. These PLCbeta isoforms were activated by the purified
      betagamma subunits of brain G proteins in the order PLCbeta3b > PLCbeta3a >
      PLCbeta2. Western blot analysis of gamma subunits of the purified platelet G
      proteins with antibodies against various standard gamma subunits revealed that
      the major component of the gamma subunit of Gi2 and Gq was gamma5, and that
      gamma7 was a minor component. Studies using various subtypes of betagamma
      subunits, betagamma2, betagamma3, and betagamma7 purified from bovine brain,
      betagamma5 from bovine lung, or betagamma12 from bovine spleen, failed to show
      differences in their ability to stimulate the isolated platelet PLCbeta isoforms.
      These results suggest that the betagamma subunits of Gi2 and Gq have similar
      efficacy in regulation of effectors in human platelets.

PMID- 9609239
TI  - Maturation of megakaryoblastic cells is accompanied by upregulation of G(s)alpha
      L subtype and increased cAMP accumulation.
AB  - In platelets and megakaryoblasts Gs, the trimeric G-protein that stimulates
      adenylyl cyclase, is present in a short, 45 kDa, and a long, 52 kDa isoform
      termed G(s)alpha-S and G(s)alpha-L, respectively. To assess the relative
      contribution of these isoforms in the cellular synthesis of cAMP, the ratio
      G(s)alpha-S/G(s)alpha-L was changed in the megakaryoblastic cell line DAMI by
      inducing cell maturation with recombinant human thrombopoietin (TPO) or the
      phorbol ester PMA. Flow cytometric analysis confirmed that this treatment induced
      a moderate (TPO) and extensive (PMA) increase in nuclear ploidy and expression of
      the glycoproteins-IIIa and -Ib. Northern blot analysis revealed downregulation of
      total Gs-mRNA after treatment of DAMI-cells with TPO and PMA. Western blot
      analysis showed significant (P < 0.05) upregulation of Gs-L with respective
      amounts of 27 +/- 4% of total Gs in untreated cells, 35 +/- 1% in TPO- and 41 +/-
      3% in PMA-treated DAMI cells (n = 3-4). DAMI cells contained 6 +/- 1 pmol
      cAMP/10(6) cells, which was not changed by treatment with TPO or PMA. In
      untreated cells this level increased to 70 +/- 9 pmol cAMP/10(6) cells after 10
      min stimulation with 1 micromol/l of the stable prostacyclin analog iloprost. The
      same stimulation with iloprost resulted in 165 +/- 32 pmol cAMP/10(6) in TPO
      treated cells and in 588 +/- 100 pmol cAMP/10(6) in cells treated with PMA. Thus,
      a shift from G(s)alpha-S to G(s)alpha-L during megakaryoblast maturation strongly
      potentiates the production of cAMP. A similar shift may occur during normal
      megakaryocyte maturation and may explain the extreme sensitivity to prostacyclin
      of platelets, which contain G(s)alpha-S and G(s)alpha-L in approximately equal
      amounts.

PMID- 9609240
TI  - Human platelet CD36 (GPIIIb, GPIV) binds to cholesteryl-hemisuccinate and can be
      purified by a simple two-step method making use of this property.
AB  - CD36, also known as GPIIIb or GPIV, is a main protein of the platelet membrane.
      Accumulating evidence implicates CD36 in the pathogenesis of atherosclerosis.
      CD36 binds to cholesteryl-hemisuccinate coupled to agarose. This binding may be
      of physiologic relevance since CD36 has a long extracellular hydrophobic region
      at its N-terminus and belongs to a family of proteins involved in lipid
      metabolism. This newly discovered binding property of CD36 was used to develop a
      rapid, efficient and gentle two-step purification method for CD36 from human
      platelets.

PMID- 9609241
TI  - CD40 engagement on endothelial cells promotes tissue factor-dependent
      procoagulant activity.
AB  - The CD40 molecule expressed on endothelial cells has been shown to transduce
      activation signals resulting in upregulation of adhesion molecules. Herein, we
      studied the impact of CD40 engagement on the induction of tissue factor (TF)
      dependent procoagulant activity (PCA) at the surface of human umbilical vein
      endothelial cells (HUVECs). First, we found that co-incubation of HUVECs with 3T6
      fibroblasts transfected with the CD40L gene (3T6-CD40L) resulted in a clear
      induction of PCA which was not observed with control untransfected fibroblasts.
      The specificity of this finding was established by inhibition experiments using
      monoclonal antibodies (mAbs) blocking CD40 or CD40L. PCA induced by CD40 ligation
      was TF-related as it was not observed in factor VII-deficient plasma and was
      associated with the accumulation of TF mRNA. To investigate the role of
      CD40/CD40L interactions in the induction of endothelial cell PCA by lymphocytes,
      interferon (IFN)-gamma-stimulated EC were incubated with T cells in the absence
      or presence of anti-CD40 or anti-CD40L mAb. The 60-70% inhibition of PCA induced
      by these mAbs but not their isotype-matched control indicated that the CD40
      pathway is involved in the induction of PCA resulting from interactions between
      activated HUVECs and T cells. We conclude that activation signals elicited by
      CD40 engagement on endothelial cells result in the induction of TF-dependent PCA.
      The CD40/CD40L pathway might therefore be involved in the development of
      prothrombic states during diseases associated with endothelial cell and T cell
      activation.

PMID- 9609242
TI  - The effects of sex steroids on plasma levels of marker proteins of endothelial
      cell functioning.
AB  - We studied thirteen male-to-female (M-->F) and ten female-to-male (F-->M)
      transsexuals who, for four months, received cross-sex treatment with,
      respectively, ethinylestradiol and cyproterone acetate, and with testosterone
      esters. We assessed the effects of treatment on plasma levels of tissue-type
      plasminogen activator (tPA), von Willebrand factor (vWF), vWF-propeptide
      (vWF:AgII) and big-endothelin-1 (big-ET-1), four proteins that are markers of
      endothelial cell functioning. We also measured urokinase-type PA (uPA) and
      plasminogen activator inhibitor-type 1 (PAI-1), which may not be endothelium
      derived but share major clearance pathways with tPA. In M-->F transsexuals, mean
      plasma levels of tPA (minus 4.4 ng/ml), big-ET-1 (minus 0.8 pg/ml), uPA (minus
      0.5 ng/ml) and PAI-1 (minus 26 ng/ml) decreased (all Ps < or =0.02). The level of
      vWF increased (plus 24%; P = 0.005), while vWF: AgII did not change (P = 0.49).
      In F-->M transsexuals, levels of big-ET-1 increased (plus 0.4 pg/ml; P = 0.02),
      while tPA, uPA and PAI-1 did not change (all Ps >0.25). In this group vWF
      decreased (minus 14%; P = 0.06), but vWF:AgII did not change (P = 0.38).
      Estrogens and androgens have clear effects on plasma levels of endothelial marker
      proteins. The mechanisms behind these effects are complex and appear to involve
      both altered secretion (big-ET-1) and processing and/or clearance (vWF and
      possibly tPA). Therefore, effects of hormones on the levels of endothelial marker
      proteins do not necessarily reflect changes in endothelial cell functioning, at
      least with regard to changes in vWF level associated with the oral administration
      of high doses of ethinylestradiol and cyproterone acetate to healthy men and the
      parenteral administration of testosterone to healthy women.

PMID- 9609243
TI  - Morphological and biochemical features affecting the antithrombotic properties of
      the aorta in adult rabbits and rabbit pups.
AB  - We hypothesised that there are important physiologic differences in arterial wall
      structure and function with respect to antithrombotic activity in the very young
      (pre-puberty) compared to adults. Electron microscopy, gel electrophoresis, and
      activity assays were used to examine differences in aorta structure and function
      comparing prepubertal rabbits (pups) to adult rabbits. Differences in endothelial
      function, extracellular matrix structure, proteoglycan (PG) distribution and
      glycosaminoglycan (GAG) content and function were shown. In both intima and
      media, total PG, chondroitin sulfate (CS) PG and heparan sulfate (HS) PG content
      were significantly increased in pups compared to adult rabbits. These findings
      corresponded to increased concentrations by mass analyses of CS GAG and DS GAG in
      aortas from pups. There was also a significant increase in antithrombin activity
      in pups due to HS GAG. In conclusion, differences in both structure and
      antithrombin activity of aortas from pups compared to adult rabbits suggest that
      young arteries may have greater antithrombotic potential that is, at least in
      part, related to increased HS GAG.

PMID- 9609244
TI  - Ancylostoma caninum anticoagulant peptide blocks metastasis in vivo and inhibits
      factor Xa binding to melanoma cells in vitro.
AB  - We evaluated the in vivo anti-metastatic activity of recombinant Ancylostoma
      caninum Anticoagulant Peptide (rAcAP), a potent (Ki = 265 pM) and specific active
      site inhibitor of human coagulation factor Xa originally isolated from
      bloodfeeding hookworms. Subcutaneous injection of SCID mice with rAcAP (0.01-0.2
      mg/mouse) prior to tail vein injection of LOX human melanoma cells resulted in a
      dose dependent reduction in pulmonary metastases. In order to elucidate potential
      mechanisms of rAcAP's anti-metastatic activity, experiments were carried out to
      identify specific interactions between factor Xa and LOX. Binding of biotinylated
      factor Xa to LOX monolayers was both specific and saturable (Kd = 15 nM).
      Competition experiments using antibodies to previously identified factor Xa
      binding proteins, including factor V/Va, effector cell protease receptor-1, and
      tissue factor pathway inhibitor failed to implicate any of these molecules as
      significant binding sites for Factor Xa. Functional prothrombinase activity was
      also supported by LOX, with a half maximal rate of thrombin generation detected
      at a factor Xa concentration of 2.4 nM. Additional competition experiments using
      an excess of either rAcAP or active site blocked factor Xa (EGR-Xa) revealed that
      most of the total factor Xa binding to LOX is mediated via interaction with the
      enzyme's active site, predicting that the vast majority of cell-associated factor
      Xa does not participate directly in thrombin generation. In addition to
      establishing two distinct mechanisms of factor Xa binding to melanoma, these data
      raise the possibility that rAcAP's antimetastatic effect in vivo might involve
      novel non-coagulant pathways, perhaps via inhibition of active-site mediated
      interactions between factor Xa and tumor cells.

PMID- 9609246
TI  - Multiplex ASA PCR for a simultaneous determination of factor V Leiden gene, G-->A
      20210 prothrombin gene and C-->T 677 MTHFR gene mutations.

PMID- 9609245
TI  - Attenuation of tissue thrombosis and hemorrhage by ala-TFPI does not account for
      its protection against E. coli--a comparative study of treated and untreated non
      surviving baboons challenged with LD100 E. coli.
AB  - This study was designed to determine the effect of a delayed infusion (T+120 min)
      of alanyl tissue factor pathway inhibitor (ala-TFPI) on the response to LD100 E.
      coli. We hypothesized that baboons treated with a low dose of TFPI (5 mg/kg)
      which did not survive would exhibit thrombosis, infarction and hemorrhage of
      target tissues such as that seen in untreated animals infused with LD100 E. coli.
      Eight baboons were infused with 5 mg/kg of ala-TFPI over a 10 h period beginning
      immediately after a 2 h infusion of LD100 E. coli (experimental group). Four
      baboons were infused with E. coli followed by a 10 h infusion of saline (control
      group). Of the 12 baboons, the 11 non-survivors (TFPI = 7 out of 8; controls = 4
      out of 4) were evaluated for the extent of thrombosis, necrosis, hemorrhage, and
      congestion of target tissues and for changes in clinical chemical parameters. We
      expected that failure to protect would correlate with failure to inhibit
      thrombosis of target tissue (8). Surprisingly ala-TFPI significantly inhibited
      thrombosis, hemorrhage and necrosis of adrenal and renal tissues and attenuated
      the rise in creatinine in the 7 treated non-survivors. The lungs of these non
      survivors, however, exhibited intra-alveolar fibrin and a mild degree of
      hemorrhage and edema. We concluded that low doses of ala-TFPI begun as late as
      T+120 in minutes failed to protect against the lethal effects of LD100 E. coli in
      spite of completely preventing thrombosis and hemorrhage in target organs, and
      that thrombosis, infarction and hemorrhage of adrenal and renal tissue are not
      part of the lethal chain of events in this IV model of E. coli sepsis.

PMID- 9609247
TI  - Detection of the 20210 A/G variation in the prothrombin gene by denaturing
      gradient gel electrophoresis (DGGE)

PMID- 9609248
TI  - Methylene tetrahydrofolate reductase (MTHFR) 677T-->C mutation and unexplained
      early pregnancy loss.

PMID- 9609249
TI  - The alpha fibrinogen T/A312 polymorphism in the ECTIM study.

PMID- 9609250
TI  - Resistance to activated protein C (APC) in childhood hydrocephalus.

PMID- 9609251
TI  - Thromboprophylaxis in antiphospholipid syndrome pregnancies with previous
      cerebral arterial thrombotic events: is warfarin preferable?

PMID- 9609252
TI  - Effect of evacuated blood collection tubes on thromboplastin calibration.

PMID- 9609253
TI  - Intraindividual variability in plasma viscosity measurements.

PMID- 9609254
TI  - Is factor VII protein concentration (FVII:Ag) a thrombotic risk indicator?

PMID- 9609255
TI  - Acquired anti-factor VII (proconvertin) inhibitor: hemorrhage and thrombosis.

PMID- 9609256
TI  - Deficiency of platelet glass bead adhesion and platelet membrane glycoprotein IV
      (CD36) in Duchenne muscular dystrophy.

PMID- 9609257
TI  - Obstetrics and gynaecology, and women's health.

PMID- 9609258
TI  - The scandal of the century.

PMID- 9609259
TI  - Practical strategies for hormone replacement therapy and risk of venous
      thromboembolism.

PMID- 9609260
TI  - Pre-eclamptic toxaemia: the role of uterine artery Doppler.

PMID- 9609261
TI  - Laparoscopic colposuspension.

PMID- 9609262
TI  - Anaemia in pregnancy in developing countries.

PMID- 9609263
TI  - The use of periurethral injectables in the treatment of genuine stress
      incontinence.

PMID- 9609264
TI  - A randomised controlled trial of antibiotic prophylaxis for vesico-vaginal
      fistula repair.
AB  - OBJECTIVE: To test the hypothesis that intravenous antibiotics given intra
      operatively reduce the failure rate of vesico-vaginal fistula repair. DESIGN: A
      single blind, randomised controlled trial. SETTING: A district hospital in Benin,
      West Africa. POPULATION: Seventy-nine women undergoing repair of an obstetric
      vesico-vaginal fistula by a single surgeon at Hopital Evangelique; two women had
      repeat operations. METHODS: Participants in the treatment group (n = 41) received
      ampicillin 500 mg intra-operatively. Controls (n = 40) received no prophylactic
      antibiotics. MAIN OUTCOME MEASURES: Failure of fistula closure and objective
      incontinence (a positive pad test) at hospital discharge. Secondary outcomes
      included febrile morbidity, other antibiotic use and urinary infection. RESULTS:
      Antibiotic prophylaxis did not reduce the odds of failed repair (OR 2.1 95% CI
      0.75-6.1) or of objective incontinence (OR 1.9; 95% CI 0.72-5.1). The women in
      the antibiotic prophylaxis group received less post-operative antibiotics and had
      less urinary infections at day 10. CONCLUSIONS: Prophylactic antibiotics should
      not be used in vesico-vaginal fistulae repair in the developing world outside
      randomised controlled trials.

PMID- 9609265
TI  - Incidence of urinary incontinence and constipation during pregnancy and
      postpartum: survey of current findings at the Rotunda Lying-In Hospital.
AB  - OBJECTIVE: To assess the impact of pregnancy upon continence and constipation.
      DESIGN: A questionnaire survey. SETTING: Maternity wards in the Rotunda Lying In
      Hospital, Dublin, Republic of Ireland. POPULATION: 7771 women who were delivered
      of liveborn infants. METHODS: Questionnaires were delivered and collected by
      physiotherapy staff as part of routine postnatal care. RESULTS: Analysis of data
      using chi2 tests showed significant differences between three parity groups
      [primigravidae, multigravidae (2-4) and multigravidae (5+)] for symptoms of both
      urinary incontinence (chi2 = 119.54, df = 2, P = 0.000) and constipation (chi2 =
      12.53, df = 3, P = 0.002); the incidence of both constipation and urinary
      incontinence increased with parity. CONCLUSION: The results of this survey have
      emphasised the relation between parity and postpartum incontinence which stresses
      the importance of early diagnosis and intervention.

PMID- 9609266
TI  - Low dose oestrogen prophylaxis for recurrent urinary tract infections in elderly
      women.
AB  - OBJECTIVE: To assess the efficacy of oral oestriol in the prevention of recurrent
      urinary tract infections in elderly women. DESIGN: Double-blind, randomised,
      parallel group, placebo controlled trial SETTING: Urogynaecology Unit at King's
      College Hospital with some women recruited from the geriatric units of St.
      Pancras Hospital and Dulwich Hospital, London (UK). PARTICIPANTS: Seventy-two
      postmenopausal women older than 60 years of age (mean 73.2 years) suffering from
      recurrent urinary tract infections. INTERVENTION: Oral oestriol (3 mg per day) or
      placebo for six months. MAIN: outcome measures Urinary tract infection rates.
      RESULTS: The study was difficult to conduct because of its design and the age of
      the participants. Oral oestriol (3 mg per day) was not shown to be superior to
      placebo in the prevention of recurrent urinary tract infections, but both
      oestriol and placebo improved urinary symptoms during the trial. CONCLUSION: The
      power of the study might have been too low to detect a significant difference
      between the groups, or oral oestriol (3 mg per day) may have been either the
      wrong dose or the wrong route of administration for this indication.

PMID- 9609267
TI  - A double-blind, placebo controlled study of postmenopausal oestrogen replacement
      therapy and carotid artery pulsatility index.
AB  - OBJECTIVE: To determine whether postmenopausal oestrogen replacement therapy
      affects carotid artery pulsatility index. DESIGN: A prospective double-blind
      placebo controlled trial. SETTING: University associated teaching hospital.
      PARTICIPANTS: Twenty-eight postmenopausal women who were more than 12 months
      postmenopausal and who had not taken exogenous oestrogen. INTERVENTIONS:
      Independent randomisation to receive oral oestradiol (2 mg daily) or placebo for
      20 to 24 weeks. MAIN OUTCOME MEASURES: Internal carotid artery Doppler
      pulsatility index, measured within one centimetre of the carotid bifurcation.
      RESULTS: Replicate data were available from 27 women. The mean pulsatility index
      decreased by -0.11 in 15 women receiving oestradiol, compared with a mean rise of
      0.05 in the 12 women who received placebo (P = 0.006, 95% CI for treatment
      difference 0.06-0.31). CONCLUSIONS: Oestrogen replacement decreases
      postmenopausal carotid artery pulsatility index, probably reflecting decreased
      peripheral vascular resistance. This is a further mechanism whereby hormone
      replacement therapy may impart cardiovascular protection.

PMID- 9609268
TI  - A comparative study using two dose regimens (200 microg or 400 microg) of vaginal
      misoprostol for pre-operative cervical dilatation in first trimester nulliparae.
AB  - OBJECTIVE: To determine the optimal dosage and dosing interval for the use of
      misoprostol administered vaginally for pre-operative cervical dilatation. DESIGN:
      Prospective double-blind randomised study. SETTING: Fertility Control Centre,
      National University Hospital, Singapore. METHODS: Women were randomly allocated
      to either the 200 microg or the 400 microg misoprostol group. Vacuum aspiration
      was performed at either three or four hours after the insertion of misoprostol
      tablets. Using Hegar's dilatator, degree of cervical dilatation before operation
      was measured. Other parameters assessed included the amount of additional
      dilatation required (if it was < Hegar 8), pre-operative and intra-operative
      blood loss, and associated side effects. RESULTS: For the 200 microg misoprostol
      group, only seven (23.3%) achieved a dilatation of > or = 8 mm compared with 29
      women (96.7%) in the 400 microg misoprostol group. The odds ratio was 95.3 (95%
      CI 10.9-830.9) for 400 microg misoprostol for successful pre-operative cervical
      dilatation of > or = 8 mm. The mean cervical dilatation for 400 microg and 200
      microg misoprostol was 8.2 mm and 6.4 mm, respectively (P < 0.001). The use of
      400 microg misoprostol with an evacuation interval of three hours appears to be
      the optimal dosage and evacuation time interval. Increasing the time interval
      beyond three hours did not confer any additional advantage on the rate of
      successful cervical dilatation but was instead associated with an increase in
      side effects such as vaginal bleeding, lower abdominal pain and the appearance of
      products of conception at the cervical os. However, besides vaginal bleeding, no
      significant differences in the frequency of these side effects were demonstrated.
      CONCLUSION: This first report on the comparison of differing dosages and time
      intervals to determine the optimal dosage treatment schedule shows that the
      vaginal application of 400 microg misoprostol for at least three hours is optimal
      for pre-operative cervical dilatation before vacuum aspiration in first trimester
      nulliparae.

PMID- 9609269
TI  - Induced abortion in the first trimester of pregnancy and risk of miscarriage.
AB  - OBJECTIVE: To analyse the relation between induced abortion and risk of
      subsequent miscarriage. DESIGN: Case-control study conducted between February
      1990 and May 1995. PARTICIPANTS: Case group included 782 women (median age 32
      years, range 14-46) admitted for spontaneous abortion (within the 12th week of
      gestation) to a network of obstetric departments in the greater Milan area. The
      control group was recruited among women who gave birth at term (> 37 weeks of
      gestation) to healthy infants on randomly selected days at the hospitals where
      cases had been identified. A total of 1543 controls (median age 30 years, range
      14-45) were interviewed. RESULTS: A total of 102 cases (13%) and 181 controls
      (12%) reported one or more induced abortions. No clear relation emerged between
      miscarriage and induced abortions. In comparison with women reporting no induced
      abortion the odds ratio (OR) for miscarriage were 1.1 (95% CI 0.8-1.4) in women
      reporting one induced abortion and 0.9 (95% CI 0.4-1.8) in women reporting two or
      more. Likewise, there was no association between time since last and age at first
      induced abortion and risk of miscarriage. CONCLUSIONS: This study did not find
      any strong association between induced and spontaneous abortion.

PMID- 9609270
TI  - Prediction of pre-eclampsia, low birthweight for gestation and prematurity by
      uterine artery blood flow velocity waveforms analysis in low risk nulliparous
      women.
AB  - OBJECTIVE: To assess the performance of four previously reported Doppler
      abnormalities of uterine artery velocity waveforms (presence of a protodiastolic
      notch, peak systolic over protodiastolic velocities (A:C ratio) > 2.5, peak
      systolic over end diastolic velocities (A:B ratio) > 90th centile, resistance
      index (RI) ([A-B]/A) > or = 0.58) in predicting pre-eclampsia, low birthweight
      and prematurity. DESIGN: Prospective cohort study. SETTING: Tertiary care
      university hospital in Quebec City. POPULATION: 1311 nulliparous women. METHODS:
      Evaluation of pulsed Doppler abnormalities of uterine artery velocity waveforms
      was carried out in 1000 and 1194 of women at 18.3 (SD 0.9) or 26.7 (SD 0.9) weeks
      of pregnancy. MAIN OUTCOME MEASURES: Pre-eclampsia, birthweight below the 10th
      centile for gestational age and spontaneous preterm birth (< 37 completed
      gestation weeks). RESULTS: Pre-eclampsia, low birthweight for gestation and
      prematurity occurred in 4%, 11% and 7% of the pregnancies, respectively. At 26
      weeks all the abnormalities of the studied Doppler indices were significantly
      associated with pre-eclampsia and low birthweight for gestation as reflected by
      the 95% confidence intervals of the positive likelihood ratios which did not
      include the value 1. However, sensitivities (26% to 34%) and positive predictive
      values (7% to 28%) were low. No Doppler indices performed significantly better
      than the others. The abnormalities of the Doppler indices were not associated
      with spontaneous prematurity. The performance of the Doppler measurements
      performed at 18 weeks was poor. CONCLUSIONS: Uterine artery Doppler velocimetry
      waveform analysis does not qualify as a reliable screening test for pre-eclampsia
      or low birthweight for gestation in low risk pregnancies but may be useful in
      selected high risk populations.

PMID- 9609271
TI  - Low sodium diet and pregnancy-induced hypertension: a multi-centre randomised
      controlled trial.
AB  - OBJECTIVE: To examine the effectiveness of the standard policy in the Netherlands
      to prescribe a sodium restricted diet to prevent or to treat mild pregnancy
      induced hypertension. DESIGN: Multi-centre randomised controlled trial between
      April 1992 and April 1994. SETTING: Seven practices of independent midwives and
      one university hospital. PARTICIPANTS: The experimental group comprised 184 women
      given a low sodium diet (< or = 50 mmol sodium/day) and a control group of 177
      women given a normal diet. Eligible women for inclusion had had a rise of blood
      pressure, or excessive weight gain or oedema during the antenatal period. The 361
      women in the trial were recruited from 2020 nulliparae, of whom 1512 (75%) gave
      informed consent at the beginning of their pregnancy to participate in the study.
      MAIN OUTCOME MEASURES: The difference between highest diastolic blood pressure
      after randomisation and diastolic blood pressure at the moment of randomisation;
      referral and admission to hospital for hypertension. RESULTS: There was no
      difference in increase of diastolic blood pressure after randomisation, the
      percentage of referral and admission to hospital for hypertension, or in
      obstetric outcome between the two groups. Urinary sodium excretion after
      randomisation in the normal diet group was significantly higher than in the low
      sodium group. CONCLUSION: Prescribing a sodium-restricted diet to prevent or to
      treat mild pregnancy-induced hypertension is not effective. Therefore there is no
      need to introduce a salt restricted diet in prenatal care, although increasing
      evidence shows that a low sodium diet prevents hypertension in non-pregnant
      individuals.

PMID- 9609273
TI  - The Ipswich Childbirth Study: 2. A randomised comparison of polyglactin 910 with
      chromic catgut for postpartum perineal repair.
AB  - OBJECTIVE: To compare polyglactin 910 sutures with chromic catgut sutures for
      postpartum perineal repair. DESIGN: A stratified randomised controlled trial,
      using a 2 x 2 factorial design. SETTING: The maternity unit at Ipswich Hospital
      NHS Trust, a district general hospital, between 1992 and 1994. SAMPLE: 1780 women
      who had sustained an episiotomy or first or second degree tear following a
      spontaneous or simple instrumental delivery. METHODS: Policies of repair with
      polyglactin 910 or chromic catgut were compared. Both groups were assessed by a
      research midwife completing questionnaires at 24 to 48 hours and at ten days
      postpartum, and by self-completed questionnaires at three months after birth.
      MAIN OUTCOME MEASURES: 1. 24 to 48 hours postpartum: perineal pain, healing; 2.
      ten days postpartum: perineal pain, healing and removal of sutures; 3. three
      months postpartum: perineal pain, removal of sutures, resuturing, dyspareunia,
      and failure to resume pain-free intercourse. RESULTS: Completed questionnaires
      were returned for 99% of women at both 24 to 48 hours and ten days and by 93% of
      women three months postpartum. The two groups were similar at trial entry.
      Significantly fewer women allocated to the polyglactin 910 reported pain in the
      previous 24 hours at both 24 to 48 hours (59% vs 67%; RR 0.89, 95% CI 0.83-0.95;
      2P < 0.01), and ten days (24% vs 29%; RR 0.81, 95% CI 0.69-0.95; 2P = 0.01). At
      three months postpartum there was no clear difference between the groups in terms
      of perineal pain, dyspareunia or failure to resume pain-free intercourse. More
      women in the polyglactin 910 group reported that some suture material had been
      removed (12% vs 7%; RR 1.62, 95% CI 1.19-2.21; 2P < 0.01). Three women in the
      polyglactin 910 group had required resuturing compared with ten in the chromic
      catgut group (RR 0.30; 95% CI 0.08-1.09; 2P = 0.1). CONCLUSIONS: Using
      polyglactin 910 rather than chromic catgut for perineal repair leads to about one
      fewer women among every 20 having perineal pain and using analgesia ten days
      postpartum. Its only apparent disadvantage is that more women, again estimated as
      1 in 20, report having material removed during healing. Data from this and other
      trials suggest that for every 100 women repaired with a polyglycolic acid-based
      material, about one fewer will require resuturing.

PMID- 9609272
TI  - The Ipswich Childbirth Study: 1. A randomised evaluation of two stage postpartum
      perineal repair leaving the skin unsutured.
AB  - OBJECTIVE: To evaluate a policy of two stage postpartum perineal repair leaving
      the skin unsutured. DESIGN: A stratified randomised controlled trial using a 2 x
      2 factorial design. SETTING: The maternity unit at Ipswich Hospital NHS Trust, a
      district general hospital, between 1992 and 1994. SAMPLE: 1780 women requiring
      surgical repair of episiotomy or first or second degree tear following a
      spontaneous or simple instrumental delivery. METHODS: A policy of two-stage
      perineal repair leaving skin unsutured was compared with a policy of three stage
      repair including skin closure with interrupted or subcuticular sutures. Both
      groups were assessed by a research midwife, blind to the allocation, completing
      questionnaires at 24 to 48 hours and 10 days postpartum, and by self-completed
      questionnaires at three months after birth. MAIN OUTCOME MEASURES: 1. 24 to 48
      hours postpartum: perineal pain; healing; 2. 10 days postpartum: perineal pain,
      healing and removal of sutures; 3. three months postpartum: perineal pain,
      removal of sutures, resuturing, dyspareunia, and failure to resume pain-free
      intercourse. RESULTS: Completed questionnaires were returned for 99% of women at
      both 24 to 48 hours and ten days and by 93% of women three months postpartum. No
      differences were detected in perineal pain at 24 to 48 hours (62% vs 64%; RR
      0.96, 95% CI 0.90-1.03; 2P = 0.3) and 10 days (25% vs 28%; RR 0.90, 95% CI 0.77
      1.06; 2P = 0.2). Significantly fewer women allocated to two-stage repair reported
      tight stitches at ten days (14% vs 18%; RR 0.77, 95% CI 0.62-0.96, 2P = 0.02);
      similar numbers of repairs were judged to be breaking down (five compared with
      seven women). At three months postpartum fewer women allocated to the two-stage
      repair reported perineal pain and more had resumed pain-free intercourse. Amongst
      women who had resumed intercourse there was a significant difference in
      dyspareunia (15% vs 19%; RR 0.80, 95% CI 0.65-0.99; 2P = 0.04). Significantly
      fewer women in the two-stage repair group (7% vs 12%; RR 0.61, 95% CI 0.45-0.83;
      2P = < 0.01) reported removal of suture material. Four women in the two-stage
      repair group had required resuturing, compared with nine allocated to the three
      stage repair. CONCLUSIONS: Two-stage repair of perineal trauma leaving the skin
      unsutured appears to reduce pain and dyspareunia three months postpartum. There
      are no apparent disadvantages, in particular no evidence of an increased risk of
      breakdown of the repair and resuturing.

PMID- 9609275
TI  - Pregnancy after heart or heart-lung transplantation: a series of 10 pregnancies.
AB  - OBJECTIVE: To evaluate pregnancy after heart or heart-lung transplantation in
      France. DESIGN: A questionnaire survey of all French centres performing heart and
      heart-lung transplants provided an exhaustive registry on pregnancy after
      transplantation. METHODS: A questionnaire was sent to 36 centres. Anonymous
      reports on transplantation and subsequent pregnancies between 1984 and 1996 were
      analysed. RESULTS: Of 1290 heart and 120 heart-lung transplantation performed
      during the study period, 10 pregnancies (seven after heart transplantation and
      three after heart-lung transplantation) were reported in nine women who were
      delivered of 11 infants. High blood pressure complicated nine pregnancies and
      severe pre-eclampsia occurred in two. One woman developed Kaposi sarcoma of the
      cervix. Delivery at 35 weeks gestation (27-39) was by caesarean section in 50%
      cases. Mean birthweight was 1990 g (700-2880g) and 50% of the infants had a
      birthweight < tenth centile. One infant developed cardiomyopathy as a condition
      inherited from her mother, and congenital hepatitis B was diagnosed in another.
      CONCLUSIONS: Pregnancy after heart and heart-lung transplantation is feasible and
      can be successful, but this should be planned when cardiac and respiratory
      functions are stable. Adequate obstetrical and genetic counselling should be
      provided.

PMID- 9609274
TI  - Endoscopic laser coagulation in the management of severe twin-to-twin transfusion
      syndrome.
AB  - OBJECTIVE: To assess the clinical effectiveness of endoscopic laser coagulation
      of placental vessels in the treatment of severe transfusion syndrome. DESIGN:
      Prospective study. SETTING: Three referral centres for the management of twin-to
      twin transfusion syndrome. POPULATION: One hundred and thirty-two pregnancies
      complicated by severe twin-to-twin transfusion syndrome, reflected by
      polyhydramnios and enlarged bladder of one twin and oligoanhydramnios and
      collapsed bladder of the other twin, presenting before 28 weeks of gestation.
      METHODS: Prospective collection of data on pre-procedure assessment, the
      procedure and the follow up were collected prospectively. Laser coagulation of
      placental vessels crossing the intertwin membrane on the chorionic surface under
      sono-endoscopic guidance, followed by amniodrainage. MAIN OUTCOME MEASURES:
      Maternal and pregnancy complications, perinatal death and morbidity were assessed
      over the last five years with follow up of survivors. RESULTS: Endoscopic laser
      was carried out at a median gestation of 21 weeks. The total number of surviving
      infants was 144 (55%) and there was at least one survivor in 97 cases (73%). At a
      minimum age of one year neurological handicap was suspected in six survivors
      (4.2%). CONCLUSIONS: The results of this multicentre study are similar to those
      in our original report on the first 45 cases. In comparison with serial
      amniodrainage, the survival rate may be similar, but the handicap rate in
      survivors appears much lower. This study stresses the need for a prospective
      study comparing these two techniques.

PMID- 9609276
TI  - Plasma from pre-eclamptic women and functional change in myometrial resistance
      arteries.
AB  - This study assesses the ability of plasma from women with pre-eclampsia to induce
      altered endothelial function in myometrial resistance vessels from normotensive
      women. Vessels from normotensive pregnant women (n = 7) were incubated with
      plasma from other pregnant women who were normotensive (n = 6) or had pre
      eclampsia (n = 7). A wire myograph was used to test the endothelium-dependent
      relaxatory response to bradykinin of preconstricted vessels. The relaxation in
      vessels incubated with plasma from women with pre-eclampsia was markedly less
      than in vessels incubated with plasma from normotensive pregnant women (P =
      0.039). This supports the theory that a plasma-borne factor contributes to the
      endothelial changes seen in pre-eclampsia.

PMID- 9609277
TI  - The effect of physiological urine dilution on pregnancy test results in
      complicated early pregnancies.
AB  - This study addresses the likelihood of false negative urine pregnancy test
      results, due to physiological urine dilution as described in some anecdotal
      reports. In this prospective study 320 pregnancy tests were performed on urine
      samples of varying concentrations obtained from 40 women, with suspected
      complications of early pregnancy, who had presented for ultrasound scans. Four
      different pregnancy tests were used and serum betahCG levels were measured
      quantitatively. Despite a mean fivefold increase in urine dilution, the pregnancy
      tests with low betahCG detection limits maintained maximal sensitivity. The
      detection of betahCG in dilute urine was adversely affected by using pregnancy
      tests with higher betahCG detection limits and these tests should be used with
      caution when assessing gynaecological emergencies.

PMID- 9609278
TI  - Variation in biochemical screening for Down's syndrome in the United Kingdom.
AB  - A questionnaire survey was undertaken of all 73 laboratories performing Down's
      syndrome screening in 1995. An estimated 352,000 tests were performed
      representing 47% of maternities. Three-quarters of these tests have ultrasound
      dating information at the time of testing. The majority of laboratories (70%)
      commenced screening at 15 weeks of gestation or later, and there was considerable
      variation in the upper limit of screening (17 to 24 weeks). Eighty-six percent of
      laboratories screened all women regardless of age. The reported Down's syndrome
      risk was based on term in 85% of laboratories. There was an inconsistent approach
      to determining and reporting high risk for trisomy 18 (Edwards' syndrome): 5%
      reported risks on report forms and 42% notified the clinicians if the risk was
      considered to be raised.

PMID- 9609279
TI  - The development of invasive vulvar cancer in a patient with Job's syndrome, a
      rare immunodeficient condition.

PMID- 9609280
TI  - Malignant eccrine poroma of the vulva.

PMID- 9609281
TI  - The changing pattern of eclampsia over a 60-year period.

PMID- 9609282
TI  - Activated protein C resistance in normal pregnancy.

PMID- 9609283
TI  - Pregnancy post-transplant: the establishment of a UK registry.

PMID- 9609284
TI  - The whole duty of obstetricians.

PMID- 9609285
TI  - Surgical experience with an implanted artificial cervical joint.
AB  - OBJECT: To assess the effectiveness of Cummins' artificial cervical joint, the
      authors reviewed the cases of 20 patients in whom the joint had been placed.
      METHODS: A review of patients' medical records and reexamination of 18 patients
      were performed. The review of the surgical experience with the implantation of
      movable stainless-steel joints in 20 patients treated for cervical myelopathy (16
      patients), cervical radiculopathy (three patients), and severe pain (one patient)
      indicated that the procedure is safe and well tolerated and does preserve
      cervical joint motion in most patients over an extended period of observation. To
      date, adjacent segmental symptomatic degenerative changes leading to further
      surgical treatment have been avoided. The joint has been placed in patients with
      advanced congenital and acquired cervical fusion and has been demonstrated to be
      stable, mobile, and biomechanically and biochemically compatible; it has shown no
      subsidence into adjacent bone. Wear debris has not occurred. CONCLUSIONS: The use
      of stainless steel in the cervical spine appears to be suitable for this joint
      replacement design.

PMID- 9609286
TI  - Long-term evaluation of reconstruction of the sellar floor with a silicone plate
      in transsphenoidal surgery.
AB  - OBJECT: The authors have used a silicone plate for reconstruction of the sellar
      floor during rhinoseptoplastic transsphenoidal surgery because it has greater
      elasticity and is easier to carve than nasal septal cartilage and sphenoid sinus
      bone. This study was designed to evaluate the usefulness of this technique based
      on the authors' experience during the past 7.6 years. METHODS: A silicone plate
      was used to reconstruct the sellar floor in 69 consecutive patients with sellar
      tumors that included 60 pituitary adenomas and nine Rathke's cleft cysts. The
      patients ranged in age from 16 to 82 years (mean 52 years). The postoperative
      position of the silicone plate could be clearly identified on sagittal or coronal
      magnetic resonance (MR) imaging as a very low intensity plate (void signal). No
      displacement or migration of the implanted silicone plate was observed on follow
      up MR imaging in any patient. Infections of the lesion such as a pituitary
      abscess were not observed clinically or radiologically in any patient. Of the 16
      patients with intraoperative cerebrospinal fluid (CSF) leakage, only one patient
      who had a ghost sella developed postoperative CSF rhinorrhea. In all seven
      patients who underwent repeated surgery for residual or recurrent tumor, the
      silicone plate that had been placed at the initial procedure was covered with a
      relatively thin fibrous capsule and the plate was well preserved. The silicone
      plate was easily removed at reoperation and was useful for detection of the
      sellar floor window made previously. CONCLUSIONS: These results indicate that a
      silicone plate can be useful for reconstruction of the sellar floor in
      rhinoseptoplastic transsphenoidal surgery.

PMID- 9609287
TI  - Spinal hamartomas: a distinct clinical entity.
AB  - OBJECT: Congenital spinal hamartomas are defined as tumors of well-differentiated
      mature elements situated in an abnormal location. In this report, the authors
      document the clinical and pathological features of spinal hamartomas in 10
      patients. METHODS: Ten patients presented with midline dorsal malformations at
      birth, initially diagnosed as teratomas or myelomeningoceles. The locations of
      the masses were variable: two were located in the thoracic region, four at the
      thoracolumbar junction, two in the lumbar region, one at the lumbosacral
      junction, and one in the sacral region. The results of the neurological
      examination were normal in nine patients. All but one mass had intact skin and
      seven had palpable bone components. Neuroimaging studies revealed widening of the
      spinal canal, heterotopic bone located dorsally in some patients, and varying
      degrees of involvement of the intraspinal contents. During surgery, six patients
      were found to have involvement of the spinal cord or cauda equina. The
      pathological characteristics of the masses included three or more of the
      following: bone, cartilage, synovial membrane, urinary tract tissue, cyst wall,
      yellow or brown fat, and nerves. The well-differentiated cellular elements, which
      formed mature structures, along with the absence of primitive cellular components
      and neoplastic characteristics are more consistent with a diagnosis of hamartoma
      than teratoma. CONCLUSIONS: In this series, the authors describe a lesion that is
      overt on physical examination, yet can have occult spinal canal involvement.
      Complete neurosurgical evaluation is essential to provide appropriate treatment
      and prognosis.

PMID- 9609288
TI  - Congenital tethered spinal cord syndrome in adults.
AB  - OBJECT: The management of tethered spinal cord syndrome with onset of
      symptomatology occurring in adulthood remains controversial, although the
      necessity of early surgery in the pediatric tethered cord syndrome population is
      well established. To ascertain the results of surgery in adult patients with this
      anomaly, the authors undertook a retrospective review of 34 cases. METHODS: The
      authors studied the hospital records of 34 consecutive patients who presented in
      adulthood with tethered cord syndrome and conducted follow-up phone interviews
      with 28 of them. The population consisted of 12 men and 22 women, ranging in age
      from 18 to 70 years (mean 34 years). The most common presenting feature was pain,
      followed by weakness and incontinence. All patients underwent surgery. The most
      common operative findings were tight filum terminale, split cord malformation,
      and lipomyelomeningocele, paralleling those observed in pediatric studies. Long
      term surgical results and patient outcome ratings were encouraging. After a mean
      clinical follow-up period of 4 years, significant improvement occurred in 22 of
      27 patients presenting with pain, 13 of 27 patients with motor or sensory
      dysfunction, and 11 of 18 patients with bowel and bladder disturbance. In
      addition, telephone interviews were obtained after a period of 8.6 years. Twenty
      two (79%) of 28 patients called the operation a long-term success; 21 (75%) of 28
      patients believed that they had significant postoperative improvement (and not
      just stabilization) in pain and/or neurological function. Surgical complications
      were generally minor. Nineteen (86%) of 22 employed patients returned to work
      after surgery. Two (33%) of six patients who were not employed before surgery
      worked full time postoperatively. Only two of the 28 patients interviewed had
      received Workers' Compensation benefits; both of these had good outcomes and
      returned to work. CONCLUSIONS: Tethered spinal cord syndrome in adults is an
      uncommon entity that can become symptomatic. Although surgery in adults involves
      greater risk of neurological injury than in children, it is a low-risk procedure
      with encouraging results. Because neurological deficits are generally
      irreversible, early surgery is recommended.

PMID- 9609289
TI  - Basilar invagination: a study based on 190 surgically treated patients.
AB  - OBJECT: The authors analyzed the cases of 190 patients with basilar invagination
      that was diagnosed on the basis of criteria laid down in 1939 by Chamberlain to
      assess the appropriate surgical procedure. METHODS: Depending on the association
      with Chiari malformation, the anomaly of basilar invagination was classified into
      two groups. Eighty-eight patients who had basilar invagination but no associated
      Chiari malformation were assigned to Group I; the remainder of the patients, who
      had both basilar invagination and Chiari malformation, were assigned to Group II.
      The principal pathological characteristic was observed to be direct brainstem
      compression due to odontoid process indentation in Group I and a reduction in
      posterior cranial fossa volume in Group II. CONCLUSIONS: Despite the anterior
      concavity of the brainstem in both groups, transoral surgery was the most
      suitable procedure for those patients in Group I and decompression of the foramen
      magnum was found to be appropriate for patients in Group II. After surgical
      decompression, a fixation procedure was found to be necessary in most Group I
      cases, but only in a small minority of Group II cases.

PMID- 9609290
TI  - Low-grade gliomas in children: tumor volume response to radiation.
AB  - OBJECT: The authors conducted a retrospective review to examine and document the
      frequency, degree, and timing of the radiologically confirmed response to
      radiotherapy of low-grade gliomas in children. METHODS: Between 1963 and 1995, 80
      patients 17 years of age or younger were referred to the London Regional Cancer
      Centre in London, Ontario after diagnosis of a low-grade glioma. All patients
      underwent surgical resection or biopsy procedures and 47 underwent radiotherapy
      (40 postoperatively and seven at the time of tumor progression). Nineteen
      patients with residual measurable lesions who received radiation therapy were
      selected for volumetric analysis of tumor response to this treatment. The extent
      and timing of response to radiation were determined by the process of comparing
      postoperative, preirradiation computerized tomography (CT) scans with
      postirradiation, follow-up CT scans. For one patient the comparison was made by
      using serial magnetic resonance images. Residual tumor was found on postoperative
      CT scans in all cases. The mean preradiotherapy tumor volume was 17.1 cm3, and
      the postradiotherapy volume was reduced to a mean of 11.5 cm3. A reduction in
      tumor volume was demonstrated in eight patients by the time of their first
      postirradiation follow-up CT scan and in two patients a slower reduction in
      volume over time was shown, bringing the total number of "responders" to 10. In
      five of these 10 patients the tumor had shown a maximum response by the time of
      the first postirradiation CT scan; the median time to response was 3.3 months. A
      25% or greater reduction in tumor volume was seen in eight (42%) of the 19
      patients. A 50% or greater reduction was noted in five (26%) of the patients. A
      complete response was demonstrated at 7, 12, and 15 months, and 5 years,
      respectively, in four patients (21%). One responder's tumor eventually increased
      in size after radiotherapy and he died of his disease. The magnitude of the
      radiographically demonstrated response to radiation did not correlate
      significantly with clinical outcome (that is, survival or symptom improvement).
      CONCLUSIONS: On the basis of this CT scan analysis of the response of low-grade
      gliomas in children to radiotherapy, the authors suggest that these lesions
      respond to radiation, as demonstrated by tumor shrinkage on serial imaging. Major
      or complete responses occur occasionally. However, low-grade gliomas in children
      mimic other benign brain tumors such as pituitary adenomas and meningiomas in
      that, although growth is frequently arrested after radiotherapy, residual tumor
      can persist for many years, illustrating that tumor shrinkage may not be a good
      measure of treatment efficacy. Nevertheless, radiation therapy can result in
      improvement of clinical symptomatology in association with or independent of
      visible tumor reduction. As radiation treatment techniques become increasingly
      conformal and because studies indicate that lower doses of radiation may be
      equally effective, improvement of symptoms may be an important consideration when
      weighing treatment options, particularly in patients with residual or
      unresectable disease.

PMID- 9609291
TI  - Mechanical dysfunction of ventriculoperitoneal shunts caused by calcification of
      the silicone rubber catheter.
AB  - OBJECT: The authors studied new and calcified shunt catheters to identify the
      prevalence of failures caused by aging materials in the shunt. Complications
      associated with these devices have various origins. Among late complications,
      fracture or migration of the system is related to the subcutaneous adhesion of
      the distal tubing in a growing child. A review of a cohort of 64 children who
      underwent shunt placement in 1980 with barium-impregnated distal catheters showed
      that 10 of these patients underwent reoperation for complications related to
      aging of the shunt material. This group represents 15% of the whole series and
      30% of those children who were followed for more than 3 years. The true impact of
      aging of materials on shunt function is probably underestimated. METHODS: The
      authors performed physical, chemical, and mechanical analyses of the retrieved
      aged catheters and also of new catheters, resulting in the following findings: 1)
      calcifications were observed only on the external surface of the catheter,
      predominantly in its subcutaneous segment at the level of the neck and anterior
      chest wall; 2) calcifications contained particles of free silicon and barium
      sulfate, signifying fragmentation of the polymer; 3) the microstructure of the
      silicone polymer was modified: microfractures and alteration of the polymeric
      network were observed; 4) silanol groups were observed on the external surface of
      the catheter; and 5) the mechanical properties of the silicone rubber were
      degraded, and the aged catheters were more brittle than the new ones, with
      ruptures at elongations and fracture energy much lower than that seen in new
      catheters. Furthermore, in vitro testing with a metastable solution of simulated
      body fluid demonstrated the critical impact of pH variations in liquid media and
      surface degradation of the catheters on the precipitation of hydroxylapatite
      crystals. CONCLUSIONS: Although most shunt complications can be addressed by
      better patient management and surgical technique, late complications appear to be
      partly related to aging of the material. Distal tubing calcifications have been
      observed in barium-impregnated catheters. The industry recently responded to
      these observations by introducing plain silicone-coated shunt tubing; further
      evaluation will show what improvement can be expected.

PMID- 9609292
TI  - Tympanic membrane displacement testing in regular assessment of intracranial
      pressure in eight children with shunted hydrocephalus.
AB  - OBJECT: The authors assessed the accuracy and repeatability of the tympanic
      membrane displacement (TMD) test, an audiometric technique that is used to
      evaluate changes in intracranial pressure (ICP) in children with shunted
      hydrocephalus. METHODS: A prospective comparative evaluation of 31 clinical
      episodes of shunt malfunction was made by using the serial TMD test and direct
      ICP measurement in eight children with shunted hydrocephalus between January 1995
      and February 1996. The volume displacement of the tympanic membrane (Vm) on
      stapedial contraction was inward for raised ICP in 11 instances and ranged from 
      120 to -539 nl (mean -263.5 nl). This was confirmed by direct ICP monitoring,
      which showed values ranging from 20 to 30 mm Hg (mean 26 mm Hg). The TMD test
      measurement (Vm) in 18 instances of low ICP ranged from 263 to 717 nl (mean 431.3
      nl); this was corroborated by direct ICP measurement, which ranged from 3 to 7 mm
      Hg (mean 4.2 mm Hg). The normal baseline Vm values obtained when patients were
      asymptomatic ranged from 98 to 197 nl (mean 110 nl). As a noninvasive diagnostic
      tool used in predicting changes in ICP, the TMD test had a sensitivity of 83% and
      specificity of 100%. The positive predictive value of the test was 100% and the
      negative predictive value was 29%. CONCLUSIONS: The TMD test can be used on a
      regular basis as a reproducible investigative tool in the assessment of ICP in
      children with shunted hydrocephalus, thereby reducing the need for invasive ICP
      monitoring. The equipment necessary to perform this testing is mobile. It will
      provide a useful serial guide to ICP abnormalities in children with shunted
      hydrocephalus.

PMID- 9609293
TI  - Changes in cerebral blood flow during PaCO2 variations in patients with severe
      closed head injury: comparison between the Fick and transcranial Doppler methods.
AB  - OBJECT: The aim of this study was to reassess whether middle cerebral artery
      blood flow velocity (MCAv) variations measured by transcranial Doppler
      ultrasonography during acute PaCO2 manipulation adequately reflect cerebral blood
      flow (CBF) changes in patients with severe closed head injury. METHODS: The study
      was performed by comparing MCAv variations to changes in CBF as assessed by
      measurements of the difference in the arteriovenous content in oxygen (AVDO2).
      The authors initiated 35 CO2 challenges in 12 patients with severe closed head
      injury during the acute stage. By simultaneous recording of systemic and cerebral
      hemodynamic parameters, 105 AVDO2 measurements were obtained. Patients were
      stratified into two groups, "high" and "low," with respect to whether their
      resting values of MCAv were greater than 100 cm/second during moderate
      hyperventilation. Four patients displayed an elevated MCAv, which was related to
      vasospasm in three cases and to hyperemia in one case. The PaCO2 and intracranial
      pressure levels were not different between the two groups. The slope of the
      regression line between 1 divided by the change in (delta)AVDO2 and deltaMCAv was
      not different from identity in the low group (1/deltaAVDO2 = 1.08 x deltaMCAv -
      0.07, r = 0.93, p < 0.001) and significantly differed (p < 0.05) from the slope
      of the high group (1/deltaAVDO2 = 1.46 x deltaMCAv - 0.4, r = 0.83, p < 0.001).
      CONCLUSIONS: In patients with severe closed head injury, MCAv variations
      adequately reflect CBF changes as assessed by AVDO2 measurements in the absence
      of a baseline increase in MCAv. These observations indicate that both moderate
      variations in PaCO2 and variations in cerebral perfusion pressure do not act
      noticeably on the diameter of the MCA. The divergence from the expected
      relationship in the high group seems to be due to the heterogeneity of CO2
      induced changes in cerebrovascular resistance between differing arterial
      territories.

PMID- 9609294
TI  - Stereotactic radiosurgery for recurrent surgically treated acromegaly: comparison
      with fractionated radiotherapy.
AB  - OBJECT: The authors tested the assumption that gamma knife radiosurgery is more
      effective than fractionated radiotherapy for the treatment of patients with
      acromegaly who have undergone unsuccessful resective surgery. Untreated and
      uncured acromegaly causes illness and death. Acromegalic patients in whom growth
      hormone and, particularly, insulin-like growth factor I are not normalized must
      undergo further treatment. METHODS: After unsuccessful operations, 16 patients
      suffering from recurrent and uncured acromegaly underwent stereotactic
      radiosurgery (25 Gy to the tumor margin, 50 Gy maximum), the outcome of which was
      compared with the result obtained in 50 patients who received fractionated
      radiotherapy (40 Gy). The cumulative distribution functions of the two groups
      (Kaplan-Meier estimate) differed significantly (p < 0.0001 in the log-rank test
      of Mantel). The mean time to simultaneous normalization of both parameters was
      1.4 years in the group treated with the gamma knife and 7.1 years in the group
      treated with fractionated radiotherapy. CONCLUSIONS: The authors suggest the use
      of stereotactic radiosurgery as the preferred treatment for recurrent acromegaly
      resulting from unsuccessfully resected tumors.

PMID- 9609295
TI  - Intrathecal baclofen infusion and subsequent orthopedic surgery in patients with
      spastic cerebral palsy.
AB  - Intrathecal baclofen infusion (IBI) is an effective treatment for spasticity
      secondary to cerebral palsy (CP). OBJECT: To assess the need for orthopedic
      surgery of the lower extremities in such cases, the authors retrospectively
      reviewed the outcome in 48 patients with spastic CP who were treated with IBI.
      METHODS: Pumps were placed in 40 patients (84%) suffering from spastic
      quadriplegia and eight patients (16%) with spastic diplegia. The patients' ages
      ranged from 5 to 43 years (mean 15 years). The mean follow-up period was 53
      months (range 24-94 months). The mean baclofen dosage was 306 microg/day (range
      25-1350 microg/day). At the time of pump placement, subsequent orthopedic surgery
      was planned in 28 patients (58%); however, only 10 (21%) underwent surgery after
      IBI therapy. In all 10 cases, the surgical procedure was planned at the time of
      initial evaluation for IBI therapy. In the remaining 18 patients, who did not
      subsequently undergo their planned orthopedic operation, it was believed that
      their lower-extremity spasticity had improved to the degree that intervention was
      no longer indicated. In addition, although six patients had undergone multiple
      orthopedic operations before their spasticity was treated, no patient required
      more than one operation after IBI treatment for spasticity. CONCLUSIONS: The
      authors conclude that IBI for treatment of spastic CP reduces the need for
      subsequent orthopedic surgery for the effects of lower-extremity spasticity. In
      patients with spastic CP and lower-extremity contractures, spasticity should be
      treated before orthopedic procedures are performed.

PMID- 9609296
TI  - Gait before and 10 years after rhizotomy in children with cerebral palsy
      spasticity.
AB  - OBJECT: Selective dorsal rhizotomy is a neurosurgical procedure performed for the
      relief of spasticity in children with cerebral palsy, but its long-term
      functional efficacy is still unknown. The authors sought to address this issue by
      means of an objective, prospective study in which quantitative gait analysis was
      used. METHODS: Eleven children with spastic diplegia (mean age at initial surgery
      7.8 years) were evaluated preoperatively in 1985 and then at 1, 3, and at least
      10 years after surgery. For comparison, 12 age-matched healthy individuals were
      also studied. Retroreflective targets were placed over the hip, knee, and ankle
      joints, and each individual's gait was videotaped. The video data were
      subsequently entered into a computer for extraction and analysis of the gait
      parameters. An analysis of variance yielded a significant time effect (p < 0.05),
      and post hoc comparisons revealed differences before and after surgery and with
      respect to the healthy volunteers. The knee and hip ranges of motion (59 degrees
      and 44 degrees, respectively, for healthy volunteers) were significantly
      restricted in children with spastic diplegia prior to surgery (41 degrees and 41
      degrees, respectively), but were within normal limits after 10 years (52 degrees
      and 45 degrees, respectively). The knee and hip midrange values (31 degrees and 3
      degrees, respectively, for healthy volunteers), indicative of posture, were
      significantly elevated preoperatively (42 degrees and 15 degrees) and increased
      sharply at 1 year (56 degrees and 18 degrees), but by 10 years they had decreased
      to within normal limits (36 degrees and 9 degrees). Step length and velocity
      improved postoperatively but were not within the normal range after 10 years. Ten
      years after surgery these patients not only had increased ranges of motion, but
      also used that movement at approximately a normal midrange point. CONCLUSIONS:
      Selective dorsal rhizotomy is an effective method for alleviating spasticity.
      Furthermore, the authors provide evidence to show that lasting functional
      benefits, as measured by improved gait, can also be obtained.

PMID- 9609297
TI  - Spasticity and strength changes as a function of selective dorsal rhizotomy.
AB  - OBJECT: The goal of this investigation was to quantify changes in hamstring
      muscle spasticity and strength in children with cerebral palsy (CP) as a function
      of their having undergone a selective dorsal rhizotomy. METHODS: Nineteen
      children with CP (CP group) and six children with able bodies (AB group)
      underwent testing with a dynamometer. For the spasticity measure, the dynamometer
      measured the resistive torque of the hamstring muscles during passive knee
      extension at four different speeds. Torque-angle data were processed to calculate
      the work done by the machine to extend the knee for each speed. Linear regression
      was used to calculate the slope of the line of best fit for the work-velocity
      data. The slope simultaneously encompassed three key elements associated with
      spasticity (velocity, resistance, and stretch) and was considered the measure of
      spasticity. For the strength test, the dynamometer moved the leg from full knee
      extension to flexion while a maximum concentric contraction of the hamstring
      muscles was performed. Torque-angle data were processed to calculate the work
      done on the machine by the child. Hamstring spasticity values for the CP group
      were significantly greater than similar values for the AB group prior to surgery;
      however, they were not significantly different after surgery. Hamstring strength
      values for the CP group remained significantly less than those for the AB group
      after surgery, but were significantly increased relative to their presurgery
      values. CONCLUSIONS: The results of spasticity testing in the present
      investigation agreed with those of previous studies, indicating a reduction in
      spasticity for the CP group. The results of strength testing did not agree with
      those in the previous literature; a significant increase in strength was observed
      for the CP group.

PMID- 9609298
TI  - Microelectrode-guided pallidotomy: technical approach and its application in
      medically intractable Parkinson's disease.
AB  - OBJECT: The authors describe the microelectrode recording and stimulation
      techniques used for localizing the caudal sensorimotor portion of the globus
      pallidus internus (GPi) and nearby structures (internal capsule and optic tract)
      in patients undergoing GPi pallidotomy. METHODS: Localization is achieved by
      developing a topographic map of the abovementioned structures based on the
      physiological characteristics of neurons in the basal ganglia and the
      microexcitable properties of the internal capsule and optic tract. The location
      of the caudal GPi can be determined by "form fitting" the physiological map on
      relevant planes of a stereotactic atlas. A sensorimotor map can be developed by
      assessing neuronal responses to passive manipulation or active movement of the
      limbs and orofacial structures. The internal capsule and optic tract,
      respectively, can be identified by the presence of stimulation-evoked movement or
      the patient's report of flashes or speckles of light that occur coincident with
      stimulation. The optic tract may also be located by identifying the neural
      response to flashes of light. The anatomical/physiological map is used to guide
      lesion placement within the sensorimotor portion of the pallidum while sparing
      nearby structures, for example, the external globus pallidus, nucleus basalis,
      optic tract, and internal capsule. The lesion location and size predicted by
      using physiological recording together with thin-slice high-resolution magnetic
      resonance imaging reconstructions of the lesion were confirmed in one patient on
      histological studies. CONCLUSIONS: These data provide important information
      concerning target identification for ablative or deep brain stimulation
      procedures in idiopathic Parkinson's disease and other movement disorders.

PMID- 9609299
TI  - Gamma knife radiosurgery for thalamotomy in parkinsonian tremor: a five-year
      experience.
AB  - OBJECT: Certain patients, for example, elderly high-risk surgical patients, may
      be unfit for radiofrequency thalamotomy to treat parkinsonian tremor. Some
      patients, when given the opportunity, may choose to avoid an invasive surgical
      procedure. The authors retrospectively reviewed their experience using gamma
      knife radiosurgery for thalamotomies in this patient subpopulation: 1) to
      determine the efficacy of the procedure; 2) to see if there is a dose-response
      relationship; 3) to review radiological findings of radiosurgical lesioning; and
      4) to assess the risks of complications. METHODS: Radiosurgical nucleus ventralis
      intermedius thalamotomy using the gamma knife unit was performed to make 38
      lesions in 24 men and 10 women (median age 73 years, range 58-87 years) over a 5
      year period. A median radiation dose of 130 Gy (range 100-165 Gy) was delivered
      to 38 nuclei (four patients underwent bilateral thalamotomy) using a single 4-mm
      collimator following classic anatomical landmarks. Twenty-nine lesions were made
      in the left nucleus ventralis intermedius thalamus for right-sided tremor.
      Patients were followed for a median of 28 months (range 6-58 months). Independent
      neurological evaluation of tremor based on the change in the Unified Parkinson's
      Disease Rating Scale tremor score was correlated with subjective patient
      evaluation. Comparison was made between a subgroup of patients in whom "low-dose"
      lesions were made (range 110-135 Gy, mean 120 Gy) and those in whom "high-dose"
      lesions were made (range 140-165 Gy, mean 160 Gy) for purposes of dose-response
      information. Four thalamotomies (10.5%) failed, four (10.5%) produced mild
      improvement, 11 (29%) produced good improvement, and 10 (26%) produced excellent
      relief of tremor. In nine thalamotomies (24%) the tremor was eliminated
      completely. The median time to onset of improvement was 2 months (range 1 week-8
      months). Concordance between an independent neurologist's evaluation and that of
      the patient was statistically significant (p < 0.001). Two patients who underwent
      unilateral thalamotomy experienced bilateral improvement in their tremor. There
      were no neurological complications. There was better tremor reduction in the high
      dose group than in the low-dose group (p < 0.04). CONCLUSIONS: Although less
      effective than other stereotactic techniques, gamma knife radiosurgery for
      thalamotomy offers tremor control with minimal risk to patients unsuited for open
      surgery.

PMID- 9609300
TI  - Combined supra/infratentorial-transsinus approach to large pineal region tumors.
AB  - OBJECT: The authors sought to confirm that the combined supra/infratentorial
      transsinus approach offers a safer means of resecting large pineal region tumors
      than other approaches currently being used. The aforementioned method provides a
      wider exposure of the pineal region with less brain retraction than the
      infratentorial-supracerebellar or the occipital-transtentorial approach alone and
      is applicable to some large and giant tumors of this area. This combined approach
      was used in six patients to remove large pineal region tumors including four
      tentorial meningiomas, one pineocytoma, and one epidermoid cyst. METHODS: The
      transverse sinus and tentorium were sectioned after review of preoperative
      angiographic studies, after taking intraoperative measurements of the venous
      pressure in the nondominant transverse sinus before and after clipping and while
      monitoring the somatosensory evoked potentials. The occipital lobe cortex and
      cerebellum were retracted slightly along the tentorium. Deep veins of the galenic
      system, the quadrigeminal area, and the tumor were well exposed. Before it was
      used for tumor resection the approach was studied in five cadaveric head
      specimens, and the projection of different approaches was compared
      radiologically. The tumors were removed in a gross-total manner in all patients,
      and none of the major veins of the galenic system was injured. Resuturing of the
      nondominant transverse sinus was performed postoperatively in one patient. One of
      the six patients experienced transient visual loss, and another suffered mild
      right sixth cranial nerve paresis; however, both recovered in 3 weeks. The wide
      exposure of the combined approach was also confirmed on radiological and
      anatomical studies. CONCLUSIONS: The combined supra/infratentorial-transsinus
      approach is preferred for the resection of certain large pineal region tumors.

PMID- 9609301
TI  - Early metabolic alterations in edematous perihematomal brain regions following
      experimental intracerebral hemorrhage.
AB  - OBJECT: The authors previously demonstrated, in a large-animal intracerebral
      hemorrhage (ICH) model, that markedly edematous ("translucent") white matter
      regions (> 10% increases in water contents) containing high levels of clot
      derived plasma proteins rapidly develop adjacent to hematomas. The goal of the
      present study was to determine the concentrations of high-energy phosphate,
      carbohydrate substrate, and lactate in these and other perihematomal white and
      gray matter regions during the early hours following experimental ICH. METHODS:
      The authors infused autologous blood (1.7 ml) into frontal lobe white matter in a
      physiologically controlled model in pigs (weighing approximately 7 kg each) and
      froze their brains in situ at 1, 3, 5, or 8 hours postinfusion. Adenosine
      triphosphate (ATP), phosphocreatine (PCr), glycogen, glucose, lactate, and water
      contents were then measured in white and gray matter located ipsi- and
      contralateral to the hematomas, and metabolite concentrations in edematous brain
      regions were corrected for dilution. In markedly edematous white matter, glycogen
      and glucose concentrations increased two- to fivefold compared with control
      during 8 hours postinfusion. Similarly, PCr levels increased several-fold by 5
      hours, whereas, except for a moderate decrease at 1 hour, ATP remained unchanged.
      Lactate was markedly increased (approximately 20 micromol/g) at all times. In
      gyral gray matter overlying the hematoma, water contents and glycogen levels were
      significantly increased at 5 and 8 hours, whereas lactate levels were increased
      two- to fourfold at all times. CONCLUSIONS: These results, which demonstrate
      normal to increased high-energy phosphate and carbohydrate substrate
      concentrations in edematous perihematomal regions during the early hours
      following ICH, are qualitatively similar to findings in other brain injury models
      in which a reduction in metabolic rate develops. Because an energy deficit is not
      present, lactate accumulation in edematous white matter is not caused by
      stimulated anaerobic glycolysis. Instead, because glutamate concentrations in the
      blood entering the brain's extracellular space during ICH are several-fold higher
      than normal levels, the authors speculate, on the basis of work reported by
      Pellerin and Magistretti, that glutamate uptake by astrocytes leads to enhanced
      aerobic glycolysis and lactate is generated at a rate that exceeds utilization.

PMID- 9609302
TI  - Neuroprotective effects of NPS 846, a novel N-methyl-D-aspartate receptor
      antagonist, after closed head trauma in rats.
AB  - OBJECT: The authors sought to determine whether 3,3-bis (3-fluorophenyl)
      propylamine (NPS 846), a novel noncompetitive N-methyl-D-aspartate receptor
      antagonist, alters outcome after closed head trauma in rats. METHODS: The
      experimental variables were: presence or absence of closed head trauma, treatment
      with NPS 846 or no treatment, and time at which the rats were killed (24 or 48
      hours). The NPS 846 (1 mg/kg) was administered intraperitoneally at 1 and 3 hours
      after closed head trauma or sham operation. Outcome measures were the
      neurological severity score (NSS), ischemic tissue volume, hemorrhagic necrosis
      volume, and specific gravity, water content, and concentrations of calcium,
      sodium, potassium, and magnesium in brain tissue. The following closed head
      trauma-induced changes in the injured hemisphere (expressed as the mean +/- the
      standard deviation) were reversed by NPS 846: decreased specific gravity of 1.035
      +/- 0.006 at 24 hours was increased to 1.042 +/- 0.004; the decreased potassium
      level of 0.583 +/- 0.231 mg/L at 48 hours and at 24 hours was increased to 2.442
      +/- 0.860 mg/L; the increased water content of 84.7 +/- 2.6% at 24 hours was
      decreased to 79.8 +/- 2%; the increased calcium level of 0.592 +/- 0.210 mg/L at
      24 hours was decreased to 0.048 +/- 0.029 mg/L; and the increased sodium level of
      2.035 +/- 0.649 mg/L was decreased to 0.631 +/- 0.102 mg/L. Administration of NPS
      846 also lowered the NSS (improved neurological status) at 48 hours (7 +/- 3) and
      caused no significant changes in ischemic tissue or hemorrhagic necrosis volumes
      in the injured hemisphere at 24 or 48 hours. CONCLUSIONS: In this model of closed
      head trauma, NPS 846 improved neurological outcome, delayed the onset of brain
      edema, and improved brain tissue ion homeostasis.

PMID- 9609303
TI  - Antivasospastic and brain-protective effects of a hydroxyl radical scavenger
      (AVS) after experimental subarachnoid hemorrhage.
AB  - OBJECT: The radical scavenger (+/-)-N,N'-propylenedinicotinamide (AVS) was shown
      recently to ameliorate delayed neurological deficits resulting from ischemia in
      patients who have had an aneurysmal subarachnoid hemorrhage (SAH). The aim of
      this study was to evaluate the effect of AVS administration after experimental
      SAH on 1) behavioral deficits; 2) angiographically confirmed basilar artery (BA)
      spasm; and 3) blood-brain barrier (BBB) permeability changes. METHODS: These
      parameters were measured by 1) using a battery of well-characterized chronic
      assessment tasks over a 5-day observation period; 2) assessing in vivo the mean
      vessel diameter 2 days after SAH; and 3) evaluating the extravasation of protein
      bound Evans Blue dye by using a spectrophotofluorimetric technique 2 days after
      SAH. Groups of eight to 10 rats received injections of 400 microl of autologous
      blood into the cisterna magna. Within 5 minutes after the surgical procedures
      were completed the rats were treated with an intravenously administered
      continuous infusion of saline (Group III) or AVS (1 mg/kg/minutes, Group IV).
      Results were compared with those in sham-operated animals treated with
      intravenously administered saline (Group I) or AVS (Group II). The AVS-treated
      rats had significantly improved balance beam scores on Days 1 to 2 (p < 0.05),
      shorter beam traverse times on Day 1 (p < 0.05), and better beam walking
      performance on Days 1 to 4 (p < 0.01), but no significant effect was seen in
      terms of SAH-related changes in body weight. Treatment with AVS also attenuated
      the SAH-induced BA spasm (p < 0.05) and decreased BBB permeability changes in
      frontal, temporal, parietal, occipital, and cerebellar cortices, and in the
      subcortical and cerebellar gray matter and brainstem (p < 0.01). CONCLUSIONS:
      These results demonstrate useful antivasospastic and brain-protective actions of
      AVS after induction of experimental SAH and provide support for observations of
      beneficial effects of AVS made in the clinical setting.

PMID- 9609304
TI  - Enhanced endogenous antioxidant activity and inhibition of cerebral vasospasm in
      rabbits by pretreatment with a nontoxic endotoxin analog, monophosphoryl lipid A.
AB  - OBJECT: Monophosphoryl lipid A (MPL) and diphosphoryl lipid (DPL) are derivatives
      of the lipopolysaccharide (endotoxin) of Salmonella minnesota strain R595.
      Monophosphoryl lipid A is relatively nontoxic and can stimulate the natural
      defense or immune system. Diphosphoryl lipid is relatively toxic; however, at
      higher concentrations, it can also stimulate an immune response. The purpose of
      the present study was to determine the effects of these endotoxin analogs on
      cerebral vasospasm after the onset of subarachnoid hemorrhage (SAH) in rabbits.
      METHODS: Intrathecal administration of MPL or DPL (5 microg/kg) was performed
      immediately before and 24 hours after induction of SAH in New Zealand White
      rabbits. Forty-eight hours after induction of SAH, the animals were killed by
      perfusion fixation for morphometric analyses of vessels or perfused with saline
      and assayed for superoxide dismutase (SOD) activity. Additional rabbits were
      administered MPL or DPL and killed 24 hours later for assessment of SOD activity;
      no SAH was induced in these animals. Experimental SAH elicited spasm of the
      basilar arteries in each group. Vasospasm was markedly attenuated in animals
      treated with MPL (p < 0.01 compared with vehicle-treated animals), but not in
      animals treated with DPL. A substantial reduction in SOD activity in the basilar
      artery accompanied the vasospasm; this loss of activity was significantly blocked
      by treatment with MPL, but not DPL. In animals that were not subjected to
      experimental SAH, MPL elicited a significant increase in SOD activity over basal
      levels, whereas DPL was ineffective. CONCLUSIONS: These data provide evidence of
      a marked protective effect of the endotoxin analog MPL against vasospasm.
      Although the mechanism(s) responsible for the protective effect of MPL remains to
      be verified, an enhancement of basal antioxidant activity and an inhibition of
      SAH-induced loss of this activity are attractive candidates. An MPL-based therapy
      could represent a useful addition to current therapies for SAH-induced cerebral
      injury.

PMID- 9609305
TI  - Enhancement of graft survival and sensorimotor behavioral recovery in rats
      undergoing transplantation with dopaminergic cells exposed to glial cell line
      derived neurotrophic factor.
AB  - OBJECT: The goal of this study was to investigate the ability of fetal
      dopaminergic neurons to improve complex sensorimotor behavior. METHODS: The
      authors obtained ventral mesencephalic tissue from 14-day-old rat fetuses. The
      cells were exposed to glial cell line-derived neurotrophic factor (GDNF) prior to
      transplantation into rats with unilateral 6-hydroxydopamine lesions of the
      dopaminergic nigrostriatal pathway. Animals that received 400,000 cells exposed
      to GDNF demonstrated significant improvement in contralateral forelimb function
      and showed improvement in rotational behavior faster than animals that received
      cells not exposed to GDNF. Increasing the number of implanted cells to 800,000
      exposed to GDNF did not result in any additional improvement in functional
      recovery. CONCLUSIONS: As neural grafting procedures in the nervous system evolve
      and genetically engineered cells or stem cells replace fetal tissue, crucial
      questions about cell number and trophic regulation will need to be addressed.
      This study demonstrates that grafting of 400,000 cells exposed to GDNF before
      transplantation has a beneficial effect in the restoration of complex
      sensorimotor behavior.

PMID- 9609306
TI  - Rerupture of coil-embolized aneurysm during long-term observation. Case report.
AB  - The authors describe the histopathological findings in a case involving rerupture
      of a recanalized aneurysm of the internal carotid artery 8 months after partial
      (95%) embolization with interlocking detachable coils. The aneurysm was filled
      with poorly organized thrombus, and its orifice was devoid of endothelial cells.
      It appears likely that a long period of observation may be required to confirm
      the complete thrombotic organization of coil-embolized aneurysms. This indicates
      that caution is needed because rupture may follow recanalization of the aneurysm.

PMID- 9609307
TI  - Symptomatic hamartoma of the spinal cord associated with neurofibromatosis type
      1. Case report.
AB  - The authors present a case in which a symptomatic hamartoma was found in the
      spinal cord of a patient with neurofibromatosis type 1 (NF-1). This 52-year-old
      woman presented with painful urinary incontinence. Magnetic resonance (MR)
      imaging revealed an intramedullary lesion within the lower thoracic spinal cord
      and conus medullaris, which was surgically removed. Pathological investigation
      showed a hamartomatous lesion consisting of glial cells, ganglion cells, abundant
      disoriented axons, and thin-walled vessels. This case provides a pathological
      correlate to the hamartomatous lesions demonstrated on MR imaging in patients
      with NF-1 and illustrates that these benign lesions may become symptomatic and
      require neurosurgical intervention.

PMID- 9609308
TI  - Malignant meningioma of the oculomotor nerve without dural attachment. Case
      report and review of the literature.
AB  - Meningiomas, thought to arise from arachnoid cap cells, are usually attached to
      the dura. Malignancy is present in approximately 1% of these tumors. The authors
      report the case of a patient with a malignant meningioma arising from the
      oculomotor nerve with no dural attachment. The patient presented with a 7-month
      history of left-sided ptosis and diplopia. Magnetic resonance imaging
      demonstrated an extrinsic mass compressing the root of the oculomotor nerve at
      its exit from the midbrain. During surgery, a left-sided subtemporal approach
      revealed the tumor to be arising from the oculomotor nerve. Histological
      investigation showed a malignant spindle cell lesion with an immunohistochemical
      profile that was consistent with malignant meningioma. To the authors' knowledge,
      this is the first documented case of a malignant meningioma arising from the
      oculomotor nerve.

PMID- 9609309
TI  - Palatal myoclonus induced by extirpation of a cerebellar astrocytoma. Case
      report.
AB  - A 45-year-old woman developed a rare case of palatal myoclonus with no other
      neurological signs after undergoing extirpation of a small cerebellar low-grade
      astrocytoma that was located in the right dentate nucleus. The palatal myoclonus
      has persisted for 4 years after the operation. Magnetic resonance T2-weighted
      imaging revealed a high-intensity lesion in the left inferior olive. Palatal
      myoclonus associated with the removal of cerebellar tumors is unusual but may
      easily be overlooked.

PMID- 9609310
TI  - Pituitary adenoma producing growth hormone and adrenocorticotropin: a
      histological, immunocytochemical, electron microscopic, and in situ hybridization
      study. Case report.
AB  - The authors report on the morphological features of a pituitary adenoma that
      produced growth hormone (GH) and adrenocorticotropic hormone (ACTH). This hormone
      combination produced by a single adenoma is extremely rare; a review of the
      available literature showed that only one previous case has been published. The
      tumor, which was removed from a 62-year-old man with acromegaly, was studied by
      histological and immunocytochemical analyses, transmission electron microscopy,
      immunoelectron microscopy, and in situ hybridization. When the authors used light
      microscopy, the tumor appeared to be a bimorphous mixed pituitary adenoma
      composed of two separate cell types: one cell population synthesized GH and the
      other ACTH. The cytogenesis of pituitary adenomas that produce more than one
      hormone is obscure. It may be that two separate cells--one somatotroph and one
      corticotroph--transformed into neoplastic cells, or that the adenoma arose in a
      common stem cell that differentiated into two separate cell types. In this case
      immunoelectron microscopy conclusively demonstrated ACTH in the secretory
      granules of several somatotrophs. This was associated with a change in the
      morphological characteristics of secretory granules. Thus it is possible that the
      tumor was originally a somatotropic adenoma that began to produce ACTH as a
      result of mutations that occurred during tumor progression.

PMID- 9609311
TI  - Benign fibroosseous lesions involving the skull base, paranasal sinuses, and
      nasal cavity. Report of two cases.
AB  - The authors report two patients with benign fibroosseous lesions involving the
      center of the skull base: a 15-year-old boy with repetitive meningitis and
      pneumocephalus and a 11-year-old boy with nasal obstruction and headache. The
      clinical diagnoses were ossifying fibroma and aneurysmal bone cyst, respectively.
      Lesions in both patients extended to the nasal cavity, the sphenoid and posterior
      ethmoid sinuses, and the skull base, where the planum sphenoidale, the sella
      turcica, the upper two-thirds of the clivus, and the medial portion of the middle
      cranial base were involved. The lesions were totally removed using an anterior
      craniofacial approach. Characteristics of these lesions and the surgical approach
      are discussed.

PMID- 9609312
TI  - Artificial cervical joint.

PMID- 9609313
TI  - Thalamotomy for parkinsonian tremor.

PMID- 9609314
TI  - Arteriovenous oxygen difference in head injury.

PMID- 9609315
TI  - Percutaneous ventriculoatrial shunts.

PMID- 9609316
TI  - Localizing pallidotomy lesions.

PMID- 9609317
TI  - Localizing pallidotomy lesions.

PMID- 9609318
TI  - Synergistic DNA damaging effects of malondialdehyde/Cu(II) in PM2 DNA and in
      human fibroblasts.
AB  - Malondialdehyde (MDA) is a product of lipid peroxidation (LPO). In combination
      with CuCl2 MDA induced single strand breaks in PM2 DNA whereas MDA or CuCl2 alone
      had no effect. Cu(II) oxidized MDA by a radical mechanism under formation of
      Cu(I). DNA strand break induction was inhibited by catalase (98%), neocuproine
      (76%) and DMSO (61%). The synergistic damaging effect of MDA and Cu(II) was also
      demonstrated in human fibroblasts measured by alkaline elution. The combination
      MDA/CuCl2 caused extensive DNA breakage while neither MDA nor CuCl2 alone induced
      DNA damage within the cell. Synergistic cytotoxic effects were observed 18 h
      after a simultaneous treatment of the cells with MDA and CuCl2 for 1 h.

PMID- 9609319
TI  - Effect of piperonyl butoxide or allopurinol on cyanide-induced lipid peroxidation
      in mouse brain.
AB  - The effect of piperonyl butoxide or allopurinol on cyanide-induced lipid
      peroxidation was investigated using homogenates from whole brain of mice. The
      brain homogenate exposed to a low concentration of potassium cyanide (10, 50, or
      100 microM) was significantly increased in their concentration of malondialdehyde
      (MDA) + 4-hydroxyalkenals (4-MDA) as compared to control samples, in a
      concentration-dependent manner. The increased lipid peroxidation induced by
      cyanide was inhibited by piperonyl butoxide (1 mM), an inhibitor of mixed
      function oxidase, but not by allopurinol (0.1 mM), an inhibitor of xanthine
      oxidase. Furthermore, when a brain homogenate heated at 86 degrees C for 1 min
      was incubated with or without cyanide at 37 degrees C for 20 min, MDA + 4-MDA
      levels in the homogenate were not changed between cyanide treatment and
      untreated. An intraperitoneal injection of piperonyl butoxide (1 g/kg)
      significantly inhibited cyanide-induced seizures in mice. These results suggest
      that cyanide-induced seizures may be partly involved in the lipid peroxidation
      produced by the heat unstable and piperonyl butoxide dependent factors in brain.

PMID- 9609320
TI  - Promotion of cultured vascular smooth muscle cell proliferation by low levels of
      cadmium.
AB  - Cadmium is a toxic heavy metal which has been shown to be a possible risk factor
      of atherosclerosis in epidemiological and experimental studies. Since intimal
      hyperplasia in vascular tissue is an important component of atherosclerosis, we
      examined the effect of cadmium on the proliferation of vascular smooth muscle
      cells cultured in a serum-free medium. It was found that cadmium at 100 nM or
      less can increase the incorporation of [3H]thymidine into the acid-insoluble
      fraction of growing bovine and rabbit aortic smooth muscle cells but not of
      growing bovine aortic endothelial cells. Although vascular smooth muscle cells
      are sensitive to cadmium cytotoxicity, no increase in the leakage of lactate
      dehydrogenase from the cells was caused by the metal at 200 nM or less in bovine
      aortic smooth muscle cells. Intracellular accumulation of radioactive calcium in
      bovine aortic smooth muscle cells was significantly increased by cadmium. It was
      therefore suggested that low levels of cadmium may promote the proliferation of
      vascular smooth muscle cells through intracellular calcium-dependent signalling
      pathway. The present study supports the hypothesis that cadmium can be a risk
      factor of atherosclerosis through dysfunction of vascular smooth muscle cells as
      well as vascular endothelial cells under certain conditions.

PMID- 9609321
TI  - Repair of wounded monolayers of cultured vascular endothelial cells after
      simultaneous exposure to lead and zinc.
AB  - We investigated the interaction between lead and zinc on the repair of wounded
      monolayers of cultured bovine aortic endothelial cells. A half area of the
      monolayers was wounded and then incubated in the presence of lead (5.0 and 10
      microM) and/or zinc (10 microM). It was morphologically observed that the
      appearance of the cells in the wounded area was strongly decreased by lead alone
      but considerably increased by zinc alone. The repair of wounded area after
      simultaneous exposure to lead and zinc showed that lead inhibits not only
      spontaneous but also zinc-promoted repair of endothelial cell layers without a
      change of the leakage of lactate dehydrogenase. Interaction between lead and zinc
      on the DNA synthesis of growing endothelial cells was similar to that on the
      repair, suggesting that the repair reflected the proliferation. In growing
      endothelial cells, the intracellular accumulation of lead was significantly
      increased by zinc; that of zinc was unaffected by lead; and that of
      metallothionein was slightly increased by zinc and lead but the effect of zinc
      was suppressed in the presence of lead. Although zinc significantly decreased the
      intracellular accumulation of radioactive calcium, lead increased it in the
      presence or absence of zinc. It was therefore concluded that lead inhibits not
      only spontaneous but also zinc-promoted repair of the damaged endothelial cell
      layers through an inhibition of the proliferation mediated by the calcium
      mediated signalling pathways and/or a disturbance of intracellular calcium
      homeostasis.

PMID- 9609322
TI  - Protective effects of extracted human-liver RNA, a known interferon inducer,
      against radiation-induced cytogenetic damage in male mice.
AB  - Cells in vitro or in vivo pre-exposed to low-dose radiation (LDR) or low
      concentrations of chemical mutagens became more resistant to large-dose radiation
      induced DNA or chromosome damage. This was known as radio-adaptive response, for
      which the exact mechanism was unclear. However, multiple cellular and molecular
      responses to LDR have been documented, for instance, the induction of some
      cytokines such as interferon (IFN). Administration of exogenous IFN to cultured
      cells or mice showed marked radio-protection. In the present study, we
      investigated the in vivo radio-protective effects of extracted human liver RNA
      (HL-RNA), a known IFN inducer, indirectly to determine the radio-protective
      action of endogenous IFN. First, mice were administered with 6.25 mg/kg HL-RNA at
      different times before exposure to radiation and the 24 h pretreatment offered
      the optimal protective action for HL-RNA on cytogenetic effects in bone marrow
      cells. When the mice were treated with different concentrations of HL-RNA for 24
      h, a wide dose-range (25-100 mg/kg) of HL-RNA resulted in a marked protection
      from X-ray-induced chromosome aberrations in both bone marrow cells and germ
      cells. In subsequent experiments, a protective effect of pretreatment with 25
      mg/kg HL-RNA for 24 h was also found for radiation-induced micronuclei in
      polychromatic erythrocytes (PCE), and inhibition of DNA repair ability
      (unscheduled DNA synthesis, UDS). These results demonstrated that HL-RNA, an IFN
      inducer, is able to offer significant cytogenetic protection from radiation,
      implying indirectly that the induction of IFN by LDR may also play a protective
      role as one of the mechanisms in the induction of the cytogenetic adaptive
      response.

PMID- 9609323
TI  - O6-methylguanine and O6-methylguanine-DNA [corrected] methyltransferase activity
      in tissues of BDF-1 mice treated with antiparasitic drugs.
AB  - Levels of the DNA promutagenic methylation damage, O6-methylguanine (O6-MeG) and
      the activity of the O6-methylguanine-DNA methyltransferase (MGMT), the enzyme
      responsible for repairing O6-MeG, were measured at various time intervals in
      tissues of BDF-I mice administered a single therapeutic dose of the
      antischistosomal agents hycanthone, oxaminiquine and metrifonate. Hycanthone
      increased O6-MeG in the liver-DNA after 6 h, then decreased by 3-fold after 48 h.
      Lower levels of the adduct and a slower rate of formation were found in the
      intestine and bladder. MGMT activities were significantly lower in the liver
      (74%) and bladder (25%) compared to control animals after 6 h, then restored by
      48 h. Oxaminiquine increased O6-MeG in all tissues, but spleen, after 6 h and
      persisted only in the bladder after 48 h. Liver and bladder tissues of these
      animals exhibited a pattern of alteration in the MGMT activity similar to that
      observed for hycanthone. Metrifonate induced a profile of O6-MeG comparable to
      that of oxaminiquine but the levels of the adduct were about 2-fold lower.
      Hepatic MGMT in these animals was significantly lower (approximately 38%) than
      the control values after 6 h, then restored by 48 h. A significant negative
      correlation was obtained between O6-MeG and MGMT activity in the liver (r=-
      0.85), intestine (r=- 0.62) and bladder (r=- 0.59). These results demonstrate
      that treatment with antischistosomal agents may lead to the formation of
      promutagenic alkylation damage in the tissue DNA and alterations in the DNA
      repair capacity.

PMID- 9609324
TI  - The role of reactive oxygen species in adriamycin and menadione-induced
      glomerular toxicity.
AB  - Redox cycling leading to oxidative stress has been proposed as the mechanism by
      which adriamycin induces glomerular toxicity in rats. The present study compares
      the extent of the oxidative stress and cytotoxicity induced by adriamycin to
      menadione (a model redox cycling quinone) in freshly isolated rat glomeruli.
      Adriamycin and menadione (25 microM) decreased de novo protein synthesis
      (measured by 3H-proline incorporation into acid-precipitable glomerular protein)
      by 50 and 85%, respectively, in 2 h. By contrast, menadione at 25 microM reduce
      glomerular membrane integrity (as assessed by lactate dehydrogenase leakage),
      adriamycin reduced membrane integrity at 500 microM adriamycin. Reactive oxygen
      species (ROS) were measured by the oxidation of dihydrodichlorofluorescein.
      Menadione (25 microM) and adriamycin (25 microM) increased ROS formation to 260
      and 156% of controls after 30 min incubation, respectively. Oxidative stress was
      assessed by measuring the intracellular level of reduced glutathione (GSH) and
      the decrease of the NADPH/NADP- ratio which stimulates the pentose phosphate
      pathway (PPP): (a) menadione (25-100 microM) reduced glomerular GSH to 10-20% of
      controls, adriamycin (25-100 microM) had no effect; (b) menadione (10 microM)
      increased PPP activity 6-fold, while adriamycin (125 microM) had only a 2-fold
      effect. Although adriamycin and menadione generate extensive ROS and decrease
      protein synthesis, there was no correlation between the extent of oxidative
      stress and cytotoxicity in glomeruli exposed to adriamycin. These results suggest
      that oxidative stress may not be the primary mechanisms by which adriamycin
      induces selective glomerular toxicity.

PMID- 9609325
TI  - Effect of cadmium(II) on the extent of oxidative DNA damage in primary brain cell
      cultures from Pleurodeles larvae.
AB  - Compounds of cadmium(II) are well-known human and animal carcinogens.
      Furthermore, they affect development. growth and brain functions at subacute
      environmental concentrations in experimental animals. We investigated the
      potential of cadmium(II) to induce oxidative DNA damage in brain cell cultures
      obtained from larvae of Pleurodeles waltl. As indicators of DNA lesions typical
      of oxygen free radicals, we determined the frequencies of DNA strand breaks and
      of DNA base modifications recognized by the bacterial formamidopyrimidine-DNA
      glycosylase (Fpg protein). DNA strand breaks were generated in a dose-dependent
      manner at concentrations of 1 microM and greater. In contrast, no significant
      increase in Fpg-sensitive sites was observed under our experimental conditions.
      However, the repair of Fpg-sensitive DNA lesions induced by visible light was
      slightly diminished at 1 microM and inhibited completely at 10 microM of
      cadmium(II), while the closure of DNA strand breaks was not affected. Our results
      show that, although cadmium is not able to induce oxidative DNA base
      modifications in larval brain cells directly, its capability to generate DNA
      strand breaks and to interfere with the repair of oxidative DNA damage could
      explain the early life stage neurotoxicity of this metal.

PMID- 9609326
TI  - The effect of methylmercury on skeletal muscle in the rat: a histopathological
      study.
AB  - Methylmercury (MeHg)-induced neurotoxicity includes skeletal muscle symptoms
      (extremity weakness and wasting, muscle cramp) in addition to ataxia and
      disturbances of sensory and visual function. The underlying mechanisms
      responsible for the skeletal muscle symptoms are still poorly understood. In this
      study the effects of MeHg exposure on skeletal muscle were investigated in rats
      receiving orally administered MeHgCl at 5 mg/kg/day for 12 days. MeHg-treated
      rats gradually lost body weight and showed muscle weakness and wasting. Seven
      days after the last MeHg dose, MeHg levels in the skeletal muscle were as high as
      those in liver, kidney, or cerebrum. The obvious histopathological finding in
      skeletal muscle was a decrease in mitochondrial enzyme activity. These changes
      were more prominent in mitochondria-rich soleus muscle than in extensor digitorum
      longus muscle. Our findings confirm that MeHg exposure disturbs mitochondrial
      energy metabolism in skeletal muscle.

PMID- 9609327
TI  - Primary slings for everyone with genuine stress incontinence? The argument
      against.

PMID- 9609328
TI  - The relationship of body mass index to intra-abdominal pressure as measured by
      multichannel cystometry.
AB  - The aim of the study was to identify the possible relationship between body mass
      index and intra-abdominal pressure as measured by multichannel cystometry. A
      retrospective chart review of patients presenting for urodynamic evaluation
      between January 1995 and March 1996 was carried out. Variables identified
      included weight, height, intra-abdominal pressure and intravesical pressure as
      recorded on multi-channel cystometrogram at first sensation in the absence of
      detrusor activity. Body mass index was defined as weight in kilograms divided by
      height in square meters. Intra-abdominal pressure was measured intravaginally
      except in those cases of complete procidentia or severe prolapse, where it was
      measured transrectally. Adequate data were available on 136 patients. The mean
      age was 60.6 years (range 30-91); mean body mass index was 27.7 kg/m2 (range 12.7
      47.7); and mean intra-abdominal pressure was 27.5 cmH2O (range 9.0-48.0). A
      strong association between intra-abdominal pressure and body mass index was
      demonstrated, with a Pearson coefficient correlation value of 0.76 (P<0.0001).
      Strong correlation was still demonstrated when those patients who had had the
      intra-abdominal pressure measured transrectally were separated out, thus
      eliminating any possible confounding factors between measurements of intra
      abdominal pressure measured transvaginally versus transrectally. In addition a
      strong correlation between intravesical pressure and body mass index was also
      demonstrated, with a Pearson coefficient correlation value of 0.71 (P<0.0001). Of
      the 136 patients, 65 (47.8%) were ultimately diagnosed as having genuine stress
      urinary incontinence (GSUI), 35 (25.7%) with GSUI and a low-pressure urethra
      (maximum urethral closure pressure of less than 20 cmH2O), and 18 (13.2%) with
      detrusor instability. The remaining 13.2% had severe prolapse. Our data
      demonstrate a significant correlation between body mass index and intra-abdominal
      pressure. These findings suggest that obesity may stress the pelvic floor
      secondary to chronic state of increased pressure, and may represent a mechanism
      which supports the widely held belief that obesity is a common factor in the
      development and recurrence of GSUI.

PMID- 9609329
TI  - The prevalence of adult female urinary incontinence in Hong Kong Chinese.
AB  - This was a community-based study to evaluate the prevalence and characteristics
      of female urinary incontinence in women aged 18 and above in the Shatin District
      of Hong Kong. Of a total of 1018 female households contacted, 362 individuals
      were successfully interviewed and 123 women (34%) reported they had experienced
      at least one episode of urinary incontinence as adults. Of these, 18.5% reported
      persistent incontinence and 15.5% reported absence of incontinence after a single
      episode of urine loss. The risk factors for incontinence revealed by this study
      were body mass index and parity. Women who had never been incontinent had a lower
      body mass index and were usually nulliparous. Most of the respondents (43.9%) who
      had urinary incontinence considered the condition to be a minor problem and did
      not seek professional advice. This investigation indicates that a territory-wide
      study should be carried out to determine the incidence of urinary incontinence
      throughout Hong Kong.

PMID- 9609330
TI  - The importance of vaginal mucosal folds at the urethral external meatus.
AB  - We report on the vaginal mucosal folds (VMF) at the urethral external meatus.
      Resection of the VMF reduces the dispersed micturition and other urinary
      symptoms.

PMID- 9609331
TI  - Vaginal topography does not correlate well with visceral position in women with
      pelvic organ prolapse.
AB  - The objective was to determine whether vaginal topography accurately predicts the
      location of the pelvic viscera on fluoroscopy in women with pelvic organ
      prolapse. Eighty-nine women undergoing preoperative evaluation for reconstructive
      pelvic surgery at a tertiary care referral practice formed the study population.
      Each woman completed a comprehensive urogynecologic history and physical
      examination, which included a quantified (POP-Q) assessment of her vaginal
      topography, as described by Bump et al. In addition each woman underwent pelvic
      floor fluoroscopy (PFF). Visceral sites were selected which corresponded
      clinically to the vaginal sites measured by the POP-Q. The most dependent portion
      of the bladder, small intestine, rectum and urethrovesical junction was measured.
      Twenty-five (28%) women had stage II prolapse, 34 (38%) had stage III prolapse,
      and 28 (32%) had stage IV prolapse. The remaining 2 women were symptomatic, with
      stage I prolapse. For the entire study population there was no correlation
      between the fluoroscopic position of the small bowel and/or rectum and any apical
      or posterior wall POP-Q site (C, Ap or Bp). There was no correlation with the
      fluoroscopic position of the UVJ at rest or with straining and the corresponding
      POP-Q site (Aa). The fluoroscopic position of the most dependent portion of the
      bladder correlated only modestly with the upper (Ba, rho = 0.51) and lower Aa,
      rho = 0.68) anterior vaginal wall POP-Q sites. In women without prior surgery (n
      = 33) there was only modest correlation between the fluoroscopic position of the
      bladder and the corresponding POP-Q site (Aa, rho = 0.71). In this unoperated
      subpopulation there was no correlation with PFF and any other POP-Q site. In
      women who had undergone prior hysterectomy (n = 25) or hysterectomy with anterior
      and/or posterior colporrhaphy (n = 17), there was only a modest correlation of
      the most dependent portion of the bladder and the upper anterior vaginal wall
      site (Bb, rho = 0.67 and rho = 0.55, respectively). It was concluded that vaginal
      topography does not reliably predict the position of the associated viscera on
      PFF in women with primary or recurrent pelvic organ prolapse.

PMID- 9609332
TI  - Thirst at work--an occupational hazard?
AB  - Of 1492 teachers 791 (53%) responded to a survey addressing whether voiding
      habits at work or behavioral factors influenced by this occupation predisposed
      women to urinary tract infection. The mean number of voids during the work day
      was 2.7 +/- 1.4; 24.5% voided infrequently (never or only once) and 26.5% voided
      four or more times during the work day; 15.8% had had a urinary tract infection
      in the preceding year. Half of the respondents made a conscious effort to drink
      less while working, to avoid needing to use the toilet. There was no association
      between the prevalence of urinary tract infection and the number of voids or
      infrequent voiding at work. Compared to women who drank the volume they desired
      at work, those who drank less had a 2.21-fold higher risk (95% CI 1.45-3.38) of
      urinary tract infection after controlling for being parous, voiding infrequently
      at work, and urge incontinence. Further study is warranted to determine whether
      modification of behavioral factors at work can reduce the incidence of urinary
      tract infections. If this association holds, public policy must be changed to
      allow workers more adequate access to toilet facilities.

PMID- 9609333
TI  - Gore-Tex sling urethral suspension in type III female urinary incontinence:
      clinical results and urodynamic changes.
AB  - The authors prospectively evaluated 24 consecutive female patients with type III
      stress urinary incontinence, ranging in age from 36 to 70 years (mean 55 years).
      All patients were operated upon and had a vesicourethral suspension by a Gore-Tex
      suburethral sling. All were evaluated urodynamically 6 and 30 months after
      surgery. In this group of patients clinical cure of incontinence was observed in
      83.3% (20) and in the remaining 4 patients it was significantly improved. In 2
      patients there was an erosion of the urethra and the sling had to be removed 3.5
      years later. Five other women remained dry but complained of occasional
      irritative symptoms, and several urinary tract infections were recorded (2-3 per
      year), which were documented by positive urine cultures. In the remaining 17
      patients no erosion was observed and no irritative symptoms were reported. The
      urodynamic evaluation revealed an excellent postoperative result both 6 months
      and 30 months after surgery.

PMID- 9609334
TI  - Use of a vaginal sponge during aerobic exercises in patients with stress urinary
      incontinence.
AB  - A newly marketed vaginal sponge intended to support the urethra was tested during
      aerobic exercise in a group of 6 women suffering from stress urinary
      incontinence. The patients performed half an hour of aerobic exercises on 2
      consecutive days, with and without the vaginal sponge. A pad was worn during
      exercise and weighed before and after. Without the vaginal sponge the patients
      had a mean loss of 7 g (range 2-18 g) during exercise. With the vaginal sponge in
      situ there was no leakage. The sponge can be recommended for use during sports in
      patients with mild to moderate incontinence.

PMID- 9609335
TI  - Human papillomavirus and bladder cancer.
AB  - Bladder cancer remains an important cause of oncological morbidity and mortality
      in women. Known etiological agents include smoking and exposure to certain
      industrial chemical compounds, though the origin of the majority of cases remains
      unknown. Human papillomavirus infection is also common in women and has been
      closely linked to the development of carcinoma of the cervix. It has been
      suggested that infection with HPV may also be an important factor in the
      subsequent development of bladder cancer. A number of studies using various
      techniques of molecular biology have looked at the relationship between HPV
      infection and bladder cancer. Although the results are somewhat conflicting, the
      overall picture would suggest little involvement of HPV in the evolution of
      bladder cancer, except possibly in a small group of patients who are
      immunocompromised.

PMID- 9609336
TI  - Pubovaginal slings: past, present and future.
AB  - Renewed interest in the pubovaginal sling procedure for stress urinary
      incontinence has occurred in response to recent reports of poor durability and
      inconsistent efficacy associated with simple cystourethropexy. Many of the
      failures are felt to represent patients with an unrecognized component of
      intrinsic sphincteric deficiency. Historically slings have a favourable cure
      rate, but have been perceived as having unacceptably high rates of prolonged
      urinary retention and secondary detrusor instability. This article reviews the
      preoperative evaluation and indications for pubovaginal slings, describes the
      evolution of the current techniques, and discusses choice of sling material,
      surgical approach, results and complications. It is hoped that this review will
      stimulate interest in this versatile but technically challenging procedure.

PMID- 9609337
TI  - Ambulatory monitoring.
AB  - Ambulatory monitoring has been hailed as the 'way forward' in urodynamic
      investigation. Its introduction has caused much excitement and there is no doubt
      that it detects more abnormalities than does conventional cystometry. It is,
      however, labour intensive and time consuming for both operator and patient, and
      requires commitment from both to be successful. No standards have been set as to
      how long a test ought to last, how many voids are required and how to interpret
      traces. To date the standard cystometric criteria of normality have been applied,
      but this would appear to be inappropriate. Several commercial companies have
      developed systems and are marketing them widely as an adjunct, or alternative, to
      conventional cystometry. It is recommended that before this technique is
      introduced into routine clinical practice it is fully evaluated, with
      standardization of terminology relating to its use.

PMID- 9609338
TI  - Adipose tissue and lipid droplet embolism following periurethral injection of
      autologous fat: case report and review of the literature.
AB  - The authors present a case of a death associated with pulmonary adipose tissue
      and lipid droplet embolism following autologous fat harvesting, periurethral
      injection and videocystourethroscopy for the treatment of recurrent genuine
      stress incontinence.

PMID- 9609339
TI  - Artificial ventricle: from the laboratory to clinical use.

PMID- 9609340
TI  - The living organism and artificial organs.

PMID- 9609341
TI  - Afterload-dependent flow fluctuation of centrifugal pump: should it be actively
      fixed?
AB  - To evaluate the clinical meaning and effects of afterload-dependent flow
      fluctuation in a centrifugal pump, concomitant measurement of flow rate and mixed
      venous oxygen saturation (SVO2) was performed in 5 cases of open heart surgery in
      which the patients underwent cardiopulmonary bypass (CPB) with the Terumo Capiox
      centrifugal pump. Continuous measurement of SVO2 using the 3M CDI System 100 was
      performed with a disposable cuvette incorporated into the drainage circuit. After
      the target flow rate of 2.4 L/min/m2 was obtained under a nonbeating condition,
      the pump rotational speed was fixed. During the cooling and low temperature
      period, SVO2 decreased as the flow rate spontaneously decreased but still stayed
      around 80% even with a 15-20% decrease in blood flow rate. This indicates that a
      luxury perfusion condition is ensured as long as the body temperature is kept
      low. In contrast, during the rewarming period, SVO2 decreased to around 70-75%
      despite a 15-25% spontaneous increase in flow rate. Although this level of SVO2
      still indicates adequate systemic perfusion, there is a possibility of regional
      hypoperfusion in patients with such conditions as cerebrovascular disease. In
      conclusion, although diligent adjustment of the physiological fluctuating flow
      rate in the centrifugal pump seems unnecessary during conventional open heart
      surgery, manual control may be necessary especially during the rewarming period,
      normothermic surgery, or circulatory assist for shocked patients. From this
      study, we also conclude that the major benefit of the afterload-independent
      autoflow control system of the centrifugal pump is the improvement of safety in
      terms of the fixed reservoir level and the handling of cardiopulmonary bypass.

PMID- 9609342
TI  - In vitro performance of a centrifugal, a mixed flow, and an axial flow blood
      pump.
AB  - We specially devised 3 types of turbo pumps, a centrifugal pump (CFP), a mixed
      flow pump (MFP), and an axial flow pump (AFP), and analyzed their in vitro
      performance. The common structural design elements were an impeller diameter of
      20 mm and sealless magnet couple driving. In vitro tests were carried out using
      heparinized fresh bovine blood. The hemolysis was comprehensively evaluated at 7
      16 points by changing the flow rate and pressure head (mapping of hemolytic
      property). The maximum efficiency (motor output to pump output) was 44.9% at
      7,000 rpm, 3.17 L/min, 191 mm Hg in the CFP; 66.3% at 7,000 rpm, 6.9 L/min, 136
      mm Hg in the MFP; and 20.6% at 9,000 rpm, 5.54 L/min, 74 mm Hg in the AFP,
      respectively. The minimum normalized index of hemolysis (NIH) (g/100 L) was 0.038
      at 5,000 rpm, 4.60 L/min, 38 mm Hg in the CFP; 0.010 at 7,000 rpm, 8.22 L/min,
      100 mm Hg in the MFP; and 0.033 at 7,000 rpm, 2.84 L/min, 48 mm Hg in the AFP,
      respectively. The best efficiency and NIH were achieved in the MFP.

PMID- 9609343
TI  - Evaluation of platelet damage in two different centrifugal pumps based on
      measurements of alpha-granule packing proteins.
AB  - Mechanical trauma caused by centrifugal pumps is usually evaluated in terms of
      hemolysis. However, platelet damage caused by centrifugal pumps has not been
      studied well. We evaluated platelet damage in 2 different centrifugal pumps, the
      Medtronic BioMedicus BP-80 and the Terumo Capiox, in vitro and compared the
      results in terms of hemolysis. To evaluate platelet damage, the rate of increase
      (RI) for beta-thromboglobulin (beta-TG) and platelet factor-4 (PF-4) were
      measured by enzyme immunoassay. RI was defined as follows: RI for beta-TG is
      deltabeta-TG/deltaN and RI for PF-4 is deltaPF-4/deltaN where deltabeta-TG is the
      increase in beta-TG, deltaPF-4 is the increase in PF-4, and deltaN is the
      increase of the passing number, which is defined in the following equation: N =
      Qt/V (t, time; V, priming volume; Q, flow rate). Each pump was tested in a mock
      circuit for 3 h under a flow rate of 5 L/min and a pressure head of 100 mm Hg
      using fresh human heparinized blood (n = 5). For comparison, the normalized index
      of hemolysis (NIH) values were calculated for both pumps. The NIH values did not
      indicate a significant difference between the Capiox and the BP-80 pumps (Capiox
      vs. BP-80, 0.0021 +/- 0.0004 vs. 0.0034 +/- 0.0007, NS). However, the RI values
      for beta-TG and PF-4 in the Capiox were significantly lower than in the BP-80
      (beta-TG, 0.198 +/- 0.047 vs. 0.376 +/- 0.049; PF-4, 0.080 +/- 0.014 vs. 0.268 +/
      0.043, p < 0.05). In conclusion, although there was no significant difference
      between the 2 pumps in terms of hemolysis, the Capiox centrifugal pump induced
      less platelet damage than the BP-80. The results suggest that measurements of RI
      for beta-TG and PF-4 are more sensitive parameters than NIH values for evaluating
      blood cell damage.

PMID- 9609344
TI  - Flow visualization as a complementary tool to hemolysis testing in the
      development of centrifugal blood pumps.
AB  - With a 250% scaled-up pump model, high speed video camera, and argon ion laser
      light sheet, flow patterns related to hemolysis were visualized and analyzed with
      4 frame particle tracking software. Different flow patterns and shear
      distributions were clarified by flow visualization for pumps modified to have
      different hemolysis levels. A combination of in vitro hemolysis tests, flow
      visualization, and CFD analysis suggested a close relationship between hemolysis
      and high shear caused by small impeller/casing gaps. Because arbitrary cross
      sections can be illuminated by laser light sheet, flow visualization is a useful
      tool in finding locations related to hemolysis in the design process of rotary
      blood pumps.

PMID- 9609345
TI  - Computational fluid dynamic analyses to establish design process of centrifugal
      blood pumps.
AB  - To establish quantitative, efficient design theories for centrifugal blood pumps,
      computational fluid dynamics (CFD) analyses were compared to the results of flow
      visualization tests and hemolysis tests, mainly on the Nikkiso centrifugal blood
      pump. The results turned out to coincide in the velocity vector plots. CFD
      analysis revealed that the smaller the gap is, the greater the shear stress
      becomes. This tendency becomes even greater with a radial gap change. Hemolysis
      study also indicated that the smaller the gap is, the greater the hemolysis. CFD
      analysis in comparison with hemolysis tests could be a useful index for
      developing blood pumps in the future.

PMID- 9609346
TI  - Washout hole flow measurement for the development of a centrifugal blood pump.
AB  - Washout holes in the impeller of a centrifugal blood pump reduce thrombus
      formation in areas where blood is apt to stagnate, especially in the back gap of
      the impeller. In this study, flow through the washout holes is quantified by
      pressure measurement and flow visualization with a 300% scaled-up model to
      understand the force driving flow through the washout holes and the flow itself.
      When external circuit resistance is constant, pressure distribution normalized by
      the square of the tip speed is constant and independent of the impeller
      rotational speed. The ratio of the flow rate through the washout holes to the
      flow rate of the external circuit is also constant. When the external circuit
      resistance increases, the pressure difference at the washout holes between the
      front and back gap of the impeller increases and generates a greater flow rate
      through the washout holes.

PMID- 9609347
TI  - Development of design methods of a centrifugal blood pump with in vitro tests,
      flow visualization, and computational fluid dynamics: results in hemolysis tests.
AB  - There are few established engineering guidelines aimed at reducing hemolysis for
      the design of centrifugal blood pumps. In this study, a fluid dynamic approach
      was applied to investigate hemolysis in centrifugal pumps. Three different
      strategies were integrated to examine the relationship between hemolysis and flow
      patterns. Hemolytic performances were evaluated in in vitro tests and compared
      with the flow patterns analyzed by flow visualization and computational fluid
      dynamic (CFD). Then our group tried to establish engineering guidelines to reduce
      hemolysis in the development of centrifugal blood pumps. The commercially
      available Nikkiso centrifugal blood pump (HPM-15) was used as a standard, and the
      dimensions of 2 types of gaps between the impeller and the casing, the axial and
      the radial gap, were varied. Four impellers with different vane outlet angles
      were also prepared and tested. Representative results of the hemolysis tests were
      as follows: The axial gaps of 0.5, 1.0, and 1.5 mm resulted in normalized index
      of hemolysis (NIH) values of 0.0028, 0.0013 and 0.0008 g/100 L, respectively. The
      radial gaps of 0.5 and 1.5 mm resulted in NIH values of 0.0012 and 0.0008 g/100
      L, respectively. The backward type vane and the standard one resulted in NIH
      values of 0.0013 and 0.0002 g/100 L, respectively. These results revealed that
      small gaps led to more hemolysis and that the backward type vane caused more
      hemolysis. Therefore, the design parameters of centrifugal blood pumps could
      affect their hemolytic performances. In flow visualization tests, vortices around
      the impeller outer tip and tongue region were observed, and their patterns varied
      with the dimensions of the gaps. CFD analysis also predicted high shear stress
      consistent with the results of the hemolysis tests. Further investigation of the
      regional flow patterns is needed to discuss the cause of the hemolysis in
      centrifugal blood pumps.

PMID- 9609348
TI  - Effect of pressure-flow relationship of centrifugal pump on in vivo hemodynamics:
      a consideration for design.
AB  - We have been developing centrifugal pumps for an implantable left ventricular
      assist device. We manufactured 2 prototype centrifugal pumps (PI, PII). These two
      have similar designs except for the PII having a volute casing and a large output
      port. To determine the differences in the hydraulic characteristics between the
      PI and PII, we carried out in vitro and in vivo experiments. In vitro study
      showed that the PII had a shallower H-Q curve than that of the PI, and the PII
      required a pump speed faster than the PI for the same flow rate and pressure
      head. On the other hand, in vivo study showed that the PII demonstrated a flow
      pulsatility greater than that of the PI at 1,900 rpm and 8 L/min although no
      significant change was observed at low pump speeds (< or = 1,500 rpm). This
      greater pulsatility consisted of a large discharge according to the small
      differential pressure during the systolic phase and a small discharge according
      to the large differential pressure during the diastolic phase. In contrast, the
      PI, having the steeper H-Q curve, showed a small discharge in the systolic phase
      and a large discharge in the diastolic phase. These results showed that
      pulsatility synchronized with the native heart beating depended on the slope of
      the H-Q curve. As a result, the slope of the H-Q curve is important to determine
      the component of pulsatility synchronized with native cardiac output. Regarding
      the slope of the H-Q curve, a pump having a volute casing and a large outlet port
      demonstrates a shallow slope in the H-Q curve. In conclusion, we suggest that a
      centrifugal pump for use in left ventricular aortic bypass should be designed
      considering the effect on the native heart pulsatility.

PMID- 9609349
TI  - Prolonged nonpulsatile left heart bypass with reduced systemic pulse pressure
      causes morphological changes in the aortic wall.
AB  - We investigated the morphological changes in the aorta due to reduced systemic
      pulse pressure in prolonged nonpulsatile left heart bypass (LHB). Nineteen adult
      goats were divided into 3 groups, the nonpulsatile group in which nonpulsatile
      LHB was conducted, the pulsatile group in which pulsatile LHB was conducted, and
      the control group used as the normal control. The average aortic pulse pressures
      were 12, 47, and 37 mm Hg, respectively. The descending aorta was subjected to
      morphological examination. In the nonpulsatile group, the wall was significantly
      thinner, and the volume ratio of smooth muscle cells (SMCs) was much lower. In
      terms of the SMC type classification, the proportion of SMCs with low activity
      and low contractility was higher, and the cell density of the SMCs was increased
      compared to those in the other groups. These results indicate that prolonged
      nonpulsatile LHB causes morphological atrophic changes in the aorta.

PMID- 9609350
TI  - Estimation of the native cardiac output from a rotary blood pump flow: in vitro
      study.
AB  - The rotary blood pump will be an implantable left ventricular assist device
      (LVAD) in the near future. However, the best control method and the
      interrelationship between the rotary blood pump and native heart functions are
      unclear. An estimation was made of the native heart cardiac output from the
      change of an LVAD's outflow waveform. The mock circulation loop was composed of
      an aortic compliance chamber, left arterial chamber, total artificial heart as a
      native heart, and a rotary blood pump that was placed as an LVAD with left
      ventricular drainage. The fast Fourier transform (FFT) technique was utilized to
      analyze the LVAD's outflow waveform and calculate the pulse power index (PPI) to
      examine a relation between the PPI and total artificial heart (TAH) output. The
      PPI increased with the increase of the TAH output; there was a positive
      correlation, and there was an inverse correlation between the PPI and the assist
      ratio. From this viewpoint, an estimation of the pulsatility change of the LVAD's
      outflow wave may indicate the native cardiac output.

PMID- 9609351
TI  - A simple neonatal mock circulation enabling pulsatility and different
      hemodynamical states for neonatal ECMO research: application to assess the effect
      of a centrifugal pump operated neonatal ECMO system on the circulation.
AB  - In neonates, extracorporeal membrane oxygenation (ECMO) is increasingly used for
      circulatory support, e.g., after cardiac surgery. For training purposes and for
      research, animal experiments are usually required, complicated by increasing
      social issues, high costs, and limited reproducibility. Therefore, we designed a
      mechanical neonatal mock circulation (NMC) model enabling pulsatility and various
      hemodynamic conditions commonly occurring in neonates. Connected to a flow and
      pressure reading interface, a computer assisted data management system was
      installed. A nonocclusive roller pump combined with stiff and elastic tubing
      segments (for aortic pressure regulation and venous capacity) as well as constant
      and variable resistance (and optionally a patent duct) are essential features of
      the NMC system. To show the investigational potential, we studied the influence
      of venoarterial and venovenous ECMO on the NMC performance during normal
      circulation, hypovolemia, high arterial resistance, the combination of both, and
      in low cardiac output. By assessing the significant effects of ECMO on the
      circulatory function of the NMC, its feasibility and investigational properties
      could be demonstrated.

PMID- 9609352
TI  - Study of left ventricular bypass using Wankel type semipulsatile blood pump.
AB  - The influence of the Wankel type semipulsatile left ventricular assistance on
      hemodynamics was investigated with a computer simulation and an animal
      experiment. A simulation circuit was constructed to express the circulatory
      system. A current source was added to create a semipulsatile blood pump. The left
      and right ventricles were replaced by variable compliances. Left heart failure
      was simulated by decreasing the amount of compliance change of the left
      ventricle. Under the condition of heart failure when semipulsatile assist flow
      increased, the mean aortic pressure (AoP), tension time index (TTI), and
      diastolic pressure time index (DPTI) increased, and the cardiac output, pulse
      pressure (PP), and pulsatility indicator (PI) decreased. In an animal experiment,
      a Wankel type blood pump was used in a calf. With the increase of the assist
      flow, AoP curves became less pulsatile, and PP and PI decreased in accordance,
      which was predicted by the numerical simulation.

PMID- 9609353
TI  - Left heart bypass using the oscillated blood flow with totally implantable
      vibrating flow pump.
AB  - Aiming at a totally implantable ventricular assist device (VAD), a vibrating flow
      pump (VFP) was developed in Tohoku University. A transcutaneous energy
      transmission system (TETS) using an amorphous fiber was developed for the totally
      implantable VAD system. The VFP works with a higher frequency than the natural
      heart of a biological system, a frequency of 10-50 Hz. In this research, animal
      experiments on left heart bypass were performed with healthy goats. Blood from
      the apex of the left ventricle was received and was sent to the aorta so that an
      adequate supporting effect of the left heart was provided. In particular, the
      depression effect of the left ventricle was obvious. As a result, sufficient
      artificial heart flow was provided. For a totally implantable type VAD, left
      heart bypass of almost 100% may become necessary in some situations. Therefore,
      apex approaches of left heart bypass may be desirable. From an anatomical
      consideration, an apex of the heart is suitable for the VFP of this totally
      implantable type. In the left heart bypass for which the apex of the heart was
      used, an almost 100% bypass was possible. This is a requirement that is important
      when waiting for recovery of sufficient cardiac function. It is also important
      that left heart circulation is maintained fully by an artificial heart of the
      complete implantation type. The VFP was considered to be useful as a totally
      implantable type artificial heart from the results.

PMID- 9609354
TI  - Control of the pulmonary arterial resistance by the use of the oscillated assist
      flow.
AB  - In the clinical application of supporting circulation, the treatment of a patient
      with pulmonary hypertension is very important. We developed the
      electromagnetically driven vibrating flow pump (VFP) as a totally implantable
      type ventricular assist system. The artificial heart driven by electromagnetic
      forces creates high speed oscillation flow around 10-50 Hz. Assistance by high
      speed oscillation flow has an interesting influence on the cardiovascular system.
      In this study, we carried out research on the influence such oscillation flow had
      on the pulmonary arterial vessels, and the supporting flow wave-form that
      controlled pulmonary vascular resistance was considered. Six healthy adult goats
      of both sexes were used in the experiments. We carried out inhalation anesthesia
      and performed intubation. The thorax was opened through left fourth rib
      resection. Right heart bypass was performed from the right atrium to the
      pulmonary artery. The flow of right heart assistance was maintained within 20-25%
      of total flow. Our purpose was to add flow of a specific high frequency to the
      right heart circulation. The hemodynamic parameters were recorded on a magnetic
      tape data recorder and input into a computer through an A-D converter. A result
      identified was that the pulmonary vascular resistance changed according to the
      alteration of the driving frequency of the VFP even during the same flow
      assistance. The resistance of the pulmonary arterial vessels became smaller when
      the driving of the VFP of 30 Hz was added to the right heart circulation. This
      was significant even when compared with continuous flow right heart assist. The
      characteristics of impedance appeared to have interesting alterations as well.
      Control of pulmonary vascular resistance by right heart assistance becomes
      possible if these results are applied. Accordingly, it may become one of the
      choices for treatment of a patient with pulmonary hypertension.

PMID- 9609355
TI  - Lipids and diabetes: a fatal combination?

PMID- 9609356
TI  - Role of non-esterified fatty acids in the pathogenesis of type 2 diabetes
      mellitus.
AB  - Over 30 years after the original description of Randle's cycle, the mechanisms by
      which elevated circulating non-esterified fatty acids might be causally related
      to glucose intolerance in Type 2 diabetes mellitus remain uncertain. This review
      examines the evidence that elevated plasma NEFA can inhibit glucose-stimulated
      insulin secretion by pancreatic beta-cells and impair glucose- and insulin
      stimulated glucose disposal by peripheral tissues. Experimental evidence
      beginning to examine the mechanisms of these phenomena is discussed.

PMID- 9609357
TI  - Cryptolepis sanguinolenta: an ethnobotanical approach to drug discovery and the
      isolation of a potentially useful new antihyperglycaemic agent.
AB  - Evidence has been published that a wide array of plant-derived active principles,
      representing numerous classes of chemical compounds, demonstrate activity
      consistent with their possible use in the treatment of patients with Type 2
      diabetes mellitus (DM). Despite these interesting observations, to date,
      metformin is the only ethical drug approved for treatment of Type 2 DM derived
      from a medicinal plant. Why is this so, given the fact that higher plants are
      such a potential source of new drugs? The answer to this rhetorical question may
      lie in the reliance of most pharmaceutical companies on random, in vitro,
      mechanism-based, high throughput screening in the initial phases of plant drug
      research. In this article we describe an alternative pathway to discovery of
      drugs for the treatment of Type 2 DM: on based on an ethnomedical approach,
      involving ethnobotany and traditional medicine. In particular, we present
      evidence that cryptolepine, an indoloquinolone alkaloid isolated from Cryptolepis
      sanguinolenta, significantly lowers glucose when given orally to a mouse model of
      diabetes. The antihyperglycaemic effect of cryptolepine leads to a significant
      decline in plasma insulin concentration, associated with evidence of an
      enhancement in insulin-mediated glucose disposal. Finally, cryptolepine increases
      glucose uptake by 3T3-L1 cells. These data permit us to conclude that an
      ethnobotanical approach to drug discovery can identify a potentially useful drug
      for the treatment of Type 2 DM.

PMID- 9609358
TI  - Atrial natriuretic peptide in type 2 diabetes mellitus: response to a
      physiological mixed meal and relationship to renal function.
AB  - Relatively few data exist on atrial natriuretic peptide (ANP) characteristics in
      Type 2 diabetes mellitus (DM). Therefore, plasma immunoreactive ANP
      concentrations were measured before and for 4 h following the ingestion of a
      physiological mixed meal in 8 newly diagnosed, normotensive, normoalbuminuric,
      patients with Type 2 DM and 6 normotensive, non-diabetic controls. In patients
      with Type 2 DM, basal plasma ANP concentrations were 4.0 +/- 2.0 and not
      significantly changed following ingestion of the meal, with peak levels of 4.9 +/
      2.8 pmol l(-1). Non-diabetic controls had higher basal plasma ANP
      concentrations, 8.7 +/- 3.4 pmol l(-1) (p < 0.05), significantly increasing to a
      peak of 11.9 +/- 6.3 pmol l(-1) at 30 min post meal. Extracellular fluid volume
      (ECV) was not different between diabetic patients and controls (15877 +/- 2679 vs
      13668 +/- 1792 ml3). Glomerular filtration rate (GFR) (isotopic clearance
      corrected for body surface area) was elevated in diabetic patients (mean +/- SD)
      130 +/- 39 vs 98 +/- 10 ml min(-1), p < 0.05). For the DM subjects, basal ANP
      levels were negatively correlated with GFR (rs - 0.74, p < 0.05) and effective
      renal plasma flow (ERPF) (rs - 0.8, p < 0.05). We conclude that patients with
      Type 2 DM demonstrate reduced basal plasma ANP concentrations which are inversely
      correlated to renal function. In contrast to non-diabetic controls, ANP in Type 2
      DM does not rise in response to feeding.

PMID- 9609359
TI  - Reducing lipid peroxidation stress of erythrocyte membrane by alpha-tocopherol
      nicotinate plays an important role in improving blood rheological properties in
      type 2 diabetic patients with retinopathy.
AB  - The effects of alpha-tocopherol nicotinate on blood viscoelasticity and viscosity
      and on lipid peroxidation stress in erythrocyte membranes in patients with Type 2
      DM were investigated. Thirteen Type 2 diabetic subjects with retinopathy were
      given alpha-tocopherol nicotinate 300 mg tds, after meals, for 3 months. The
      treatment resulted in significant reductions of blood viscosity at different
      shear rates (e.g. -2.23 +/- 2.82 p<0.015, gamma = 1.5 s(-1)) and viscoelasticity
      (p<0.004); resistance of erythrocyte deformation (p<0.001) and lipid peroxidation
      stress in red cell membrane (malondialdehyde or MDA reduced by 0.17 +/- 0.13 nmol
      l(-1) p<0.005). Plasma viscosity, red cell rigidity, and HbA1c were unchanged.
      There were negative linear correlations between the indices of red cell
      deformability and the levels of MDA of red cell membrane both pre- and post
      treatment (e.g. R = -0.79, p<0.001; R = -0.78, p<0.002, n = 13; pre- and post-,
      respectively). We suggest that the improvements of rheological properties of
      blood and red cell deformability by alpha-tocopherol nicotinate are mainly
      attributed to reducing lipid peroxidation stress on membrane of red blood cells.
      The treatment may be useful in slowing deterioration of microangiopathy in Type 2
      DM.

PMID- 9609360
TI  - Lipid but not glycaemic parameters predict total mortality from type 2 diabetes
      mellitus in Canterbury, New Zealand.
AB  - A cohort of 447 subjects with Type 2 diabetes mellitus (208 male, 239 female; age
      range 30-82, median 62 years; and of predominantly European origin) was
      characterized in a clinic survey in 1989. Individual status (dead or alive) at 1
      June 1995 was ascertained. Mortality rates were compared with the general New
      Zealand population by calculating standardized mortality ratios (SMR) and the
      hazard ratio (HR) of prognostic factors evaluated with Cox's proportional hazards
      model. At 6 years, 289 subjects were confirmed as alive and 133 as dead; only 25
      were untraceable. Six-year survival for the cohort was 70% (95% CI 66-74). SMR
      was 2.53 (95% CI 1.99-2.68) for the female cohort and 2.03 (95% CI 1.60-2.59) for
      the male cohort. Factors assessed at baseline (1989) that were independently
      prognostic of total mortality included age, male sex, pre-existing coronary
      artery disease (CAD) (HR 2.2, 95% CI 1.5-3.3) and plasma cholesterol (HR for 1.4
      mmol l(-1) change: 1.49, 95% CI 1.2-1.9). HDL-cholesterol was protective in women
      (HR for 0.4 mmol l(-1) change: 0.72, 95% CI 0.51-1.00) but not men. Glycated
      haemoglobin was not a significant predictor of total mortality. Predictors of CAD
      mortality (in those subjects free of CAD in 1989) included plasma cholesterol (HR
      for 1.4 mmol l(-1) change: 1.86 95% CI 1.20-2.89), glycated haemoglobin (HR for
      1.8% change: 1.9 95% CI 1.04-3.47), male sex, peripheral vascular disease, and
      smoking. There is therefore increased mortality in Type 2 diabetic subjects in
      Canterbury, New Zealand. HDL-cholesterol is protective against total mortality in
      females.

PMID- 9609361
TI  - Carbohydrate malabsorption following acarbose administration.
AB  - Carbohydrate absorption was assessed during acarbose administration to
      investigate the actions of this drug. In 7 healthy volunteers, breath hydrogen
      concentration was measured at 15-min intervals after administration of 6 g of
      lactulose, and continued until 4 h after the breath hydrogen level exceeded its
      pretreatment value by > or =10 ppm, then the amount of undigested carbohydrate
      was calculated following administration of various doses of acarbose and Ensure
      Liquid. Breath hydrogen data were also obtained before and after administration
      of acarbose to 8 patients with Type 2 diabetes mellitus for 2 and 4 months. After
      administration of 50 mg of acarbose with 250 ml or 500 ml of Ensure, the mean
      amount of unabsorbed carbohydrate was 5.3 g and 7.7 g, respectively, while
      unabsorbed carbohydrate increased to 10.8 g after 100 mg of acarbose with 500 ml
      of Ensure. In the diabetic patients, breath hydrogen excretion decreased to 31.6%
      of baseline after 2 months of acarbose administration, indicating decreased
      carbohydrate malabsorption. Despite this, the haemoglobin A1c level remained
      stable after 5 months. In conclusion, the extent of carbohydrate malabsorption
      depended on the acarbose dose and the carbohydrate load. Although carbohydrate
      malabsorption decreased with continued acarbose administration, the improvement
      of glycaemic control was maintained.

PMID- 9609362
TI  - Perceived symptoms of hypoglycaemia in elderly type 2 diabetic patients treated
      with insulin.
AB  - Elderly insulin-treated diabetic patients have a high risk of severe
      hypoglycaemia, yet their hypoglycaemic symptom profile has attracted little
      research. In this study, the frequency and intensity of symptoms of hypoglycaemia
      were recorded using a validated questionnaire in 132 insulin-treated diabetic
      patients, aged 70 years or more. Principal components analysis (PCA) was used to
      discover the factorial structure of the symptoms. Lightheadedness and
      unsteadiness were prominent symptoms in the elderly patients. PCA suggested three
      separate groups of symptoms: (1) those related specifically to impairment of co
      ordination and articulation; (2) more general neuroglycopenic symptoms, and (3)
      autonomic symptoms. The frequency and classification of hypoglycaemic symptoms in
      this elderly population is different from those seen in younger diabetic patients
      treated with insulin. Neurological symptoms of hypoglycaemia were more commonly
      reported and may be misinterpreted as features of cerebrovascular disease. Health
      professionals and carers involved in the treatment and education of diabetic
      patients should be aware of the age-specific differences in hypoglycaemic
      symptoms.

PMID- 9609363
TI  - Autonomic function in children with type 1 diabetes mellitus.
AB  - We investigated autonomic function in 58 children and young adults with Type 1
      diabetes mellitus (aged 7-22 years, duration from 3 to 18, 8.6 +/- 3.4 years) and
      in 74 healthy controls (6-21 years) using power spectral analysis of blood
      pressure and heart rate in addition to conventional standard autonomic function
      tests: deep breathing, the Valsalva manoeuvre, and a standing test. None of the
      diabetic patients were symptomatic. Reproducibility of the tests was assessed by
      determining the coefficient of variation in 9 controls (7.8-37.7%). Thirteen per
      cent of the subjects had difficulty in adequately performing the Valsalva
      manoeuvre. After adjustment for age, sex, body mass index, and respiratory
      frequency, results of the Valsalva manoeuvre and deep breathing were not
      different between patients and controls and there was no significant postural
      reduction in systolic blood pressure (> or = 20 mmHg) in the patients. Heart rate
      variation in the supine position during natural breathing was low in patients,
      although power spectral analysis of heart rate variation did not show a
      significant decrease in the power density in the high and the low frequency in
      patients compared to healthy controls. Beat-to-beat blood pressure fluctuation
      was significantly lower in patients and correlated with metabolic control (mean
      annual haemoglobin A1c), but not with disease duration and was abnormal in 7
      diabetic children (12%). In contrast, tests of vagal activity were not impaired
      in the patients in this age range. We concluded that vagal involvement in Type 1
      diabetic patients determined by spectral analysis of R-R intervals in addition to
      conventional tests is uncommon, but that beat-to-beat blood pressure variation
      was more likely to be affected.

PMID- 9609364
TI  - Conservative surgical approach versus non-surgical management for diabetic
      neuropathic foot ulcers: a randomized trial.
AB  - To test the efficacy of surgical treatment of non-infected neuropathic foot
      ulcers compared to conventional non-surgical management, a group of diabetic
      outpatients attending our diabetic foot clinic were studied. All patients who
      came to the clinic for the first time from January to December 1995 inclusive
      with an uncomplicated neuropathic ulcer were randomized into two groups. Group A
      received conservative treatment, consisting of relief of weight-bearing, regular
      dressings; group B underwent surgical excision, eventual debridement or removal
      of bone segments underlying the lesion and surgical closure. Healing rate,
      healing time, prevalence of infection, relapse during a 6-month period following
      intervention and subjective discomfort were assessed. Twenty-four ulcers in 21
      patients were treated in group A (17 Type 2 DM/3 Type 1 DM, age 63.24 +/- 13.46
      yr, duration of diabetes 18.2 +/- 8.41 yr, HbA1c 9.5 +/- 3.8%) and 22 ulcers in
      21 patients in group B (19 Type 2 DM/2 Type 1 DM, age 65.53 +/- 9.87yr, duration
      of diabetes 16.84 +/- 10.61 yr; HbA1c 8.9 +/- 2.2%). Healing rate was lower
      (79.2% = 19/24 ulcers) in group A than in group B (95.5% = 21/22 ulcers; p <
      0.05), and healing time was longer (128.9 +/- 86.60 days vs 46.73 +/- 38.94 days;
      p < 0.001). Infective complications occurred significantly more often in group A
      patients (3/24, 12.5% vs 1/22, 4.5%; p < 0.05), as did relapses of ulcerations (8
      vs 3; p < 0.01). There were only two minor perioperative complications in group B
      patients. Patients reported a higher degree of satisfaction in group B (p < 0.01)
      as well as lower discomfort (p < 0.05) and restrictions (p < 0.05). Thus surgical
      treatment of neuropathic foot ulcers in diabetic patients proved to be an
      effective approach compared to conventional treatment in terms of healing time,
      complications, and relapses, and can be safely performed in an outpatient
      setting.

PMID- 9609365
TI  - Parental history of hypertension and parental history of diabetes and
      microvascular complications in insulin-dependent diabetes mellitus: the EURODIAB
      IDDM Complications Study.
AB  - Diabetic nephropathy clusters in families, suggesting an inherited
      predisposition. Parental history of hypertension and of Type 2 diabetes mellitus
      have been associated with nephropathy in offspring with Type 1 diabetes in some
      studies but not in others. The associations of parental history of hypertension
      and of diabetes with both albuminuria and proliferative retinopathy were studied
      in a large cross-sectional study of 3250 patients with Type 1 diabetes, from 16
      European countries. Albuminuria was associated with hypertension in a parent (p <
      0.01 in men, p < 0.05 in women), adjusted for age. Patients with a parental
      history of hypertension had a higher prevalence of hypertension (p < 0.001 in
      men, p < 0.01 in women) and a higher prevalence of parental diabetes (p < 0.001
      in men, p < 0.001 in women). The association of albuminuria with parental
      hypertension was independent of parental diabetes in men but not women (OR = 1.28
      in men p = 0.04, OR = 1.25 in women p = 0.09) and was not independent of
      hypertension in the patient him/herself in either sex. Albuminuria was associated
      with parental diabetes in women only (OR = 1.36, p = 0.04). This association was
      independent of both parental hypertension and hypertension in the patient
      herself. Proliferative retinopathy was not associated with parental hypertension
      or diabetes. The implications of these data are that both candidate genes for
      hypertension and Type 2 diabetes should be considered in the search for the
      genetic determinants of diabetic nephropathy.

PMID- 9609366
TI  - Dobutamine stress echocardiography: false positive scans in proteinuric patients
      with type 1 diabetes mellitus at high risk of ischaemic heart disease.
AB  - Patients with Type 1 diabetes mellitus have an increased risk of ischaemic heart
      disease (IHD). When diabetes is complicated by nephropathy this risk is further
      increased and asymptomatic IHD is common. New techniques for non-invasive cardiac
      evaluation are now available and one of these, Dobutamine Stress Echocardiography
      (DSE), was studied in subjects with Type 1 DM and nephropathy who had no evidence
      of IHD. DSE was performed on 18 subjects (13 male, 5 female; mean age 37.8 +/-
      3.4 years), diabetes duration 23.7 +/- 1.2 years and nephropathy diagnosed for
      10.9 +/- 1.3 years. There were 7 (38%) positive scans-suggesting asymptomatic
      IHD; 16.7% of subjects studied had a significant arrhythmia. Coronary angiography
      was performed in 6 of the 7 subjects with positive DSEs and was positive in only
      2. These results suggest that DSE has a high rate of false positive results in
      Type 1 DM patients suffering from nephropathy and may limit its usefulness in
      these subjects.

PMID- 9609367
TI  - Onset of type 1 diabetes mellitus in infancy after enterovirus infections.
AB  - Enterovirus infections may initiate and accelerate the beta-cell damaging process
      leading to Type 1 (insulin-dependent) diabetes mellitus (Type 1 DM). Recent
      prospective studies have suggested that this can happen long before overt disease
      and even in utero. We describe an infant, followed regularly from birth, who
      progressed to clinical Type 1 DM at the age of 14 months. He had a strong
      enterovirus exposure exceptionally early in life; the first enterovirus infection
      occurred before the age of 3 months and the second between the age of 9 and 12
      months. The first infection probably occurred at birth, when the child had
      symptoms of a respiratory infection. This infection was followed by the
      appearance of beta-cell autoimmunity, and clinical Type 1 DM was diagnosed
      shortly after the second infection. The child had a low level of maternal
      enterovirus antibodies and short duration of breast-feeding, both associated with
      increased risk for enterovirus infections during the fetal period and infancy.
      This case fits with the current hypothesis that enterovirus infections can induce
      the process resulting in Type 1 DM, especially when occurring early in life.
      Furthermore, this demonstrates the feasibility of the present study design, which
      is applicable also in large-scale birth-cohort studies.

PMID- 9609368
TI  - Hyperglycaemia due to insulin resistance caused by interferon-gamma.
AB  - Marked hyperglycaemia (30.9 mmol l(-1)) during interferon-gamma (IFN-gamma)
      therapy for asymptomatic recurrent renal cancer as multiple lung metastases in a
      52-year-old man is described. Although the involvement of IFN-gamma has been
      reported in the development of autoimmune diabetes, in this case, antibodies
      against pancreatic beta-cells including anti-islet cell antibody (ICA) and anti
      glutamic acid decarboxylase (GAD) antibody were negative. Moreover, serum level
      of immunoreactive insulin (IRI) (11 microU ml(-1) at fasting) and urinary
      excretion of C-peptide (108 microg day(-1), reference range: 20-130) suggested
      insulin resistance, supported by results of insulin tolerance tests. With insulin
      therapy and cessation of IFN-gamma, fasting blood glucose concentration returned
      to 6.2 mmol l(-1), and insulin therapy was discontinued. The injection of IFN
      gamma may cause hyperglycaemia because of insulin resistance, rather than beta
      cell injury.

PMID- 9609369
TI  - Evaluation of antimicrobial efficacy and release pattern of tetracycline and
      metronidazole using a local delivery system.
AB  - The present study compared the effectiveness of two antimicrobials, tetracycline
      and metronidazole, in reducing subgingival microorganisms in periodontal pockets
      using an ethyl cellulose strip as the delivery medium. The study involved 30
      patients, with a minimum of 3 periodontal pockets with probing depths > 6 mm
      throughout the oral cavity. Patients were given supragingival scaling and then
      divided into 5 groups, depending on the length of time the medication was in
      place. Sites were marked for tetracycline, metronidazole, and placebo. Sites were
      wiped and isolated, and baseline microbiology samples were taken for Gram
      staining and culture methods. After treatment, subgingival microbiological
      samples were taken again. The ethyl cellulose strips were removed and analyzed
      for any remaining drug. Results showed that tetracycline and metronidazole can
      both be applied locally to periodontal sites using ethyl cellulose strips and
      markedly suppress the subgingival bacteria over a period of several days. The
      tetracycline showed a faster release; however, the metronidazole required a
      lesser concentration to achieve complete reduction of the subgingival flora.

PMID- 9609370
TI  - Histologic findings after implantation and evaluation of different grafting
      materials and titanium micro screws into extraction sockets: case reports.
AB  - The purpose of this study was to compare extraction socket healing in 8 patients
      after implantation with either xenogenic bovine bone (n=5 sites), demineralized
      freeze-dried bone (DFDBA) (n=3 sites), autologous bone (n=3 sites), or human bone
      morphogenetic proteins in an osteocalcein/osteonectin carrier (hBMP/NCP) (n=2
      sites). Three of the patients received 6 commercially pure micro screws which
      were fixed into extraction sockets, after which the sockets were implanted with
      either bovine bone (n=3 sites), DFDBA (n=2 sites) or intraoral autologous bone
      (n=1 site). Biopsies of the extraction sockets were taken from 3 to 6 months
      after treatment (average, 4.6 months). For comparison of healing between the
      implanted materials, histologic evaluation and bone scores were determined. Bone
      scores of 0 indicated an absence of new bone, with dead implanted bone particles
      entrapped within connective tissue, while a score of 3 indicated the entire field
      consisted of vital bone. Biopsies from bovine bone sockets revealed dead
      implanted particles surrounded by connective tissue. Isolated sections showed
      host bone in contact with the bovine bone particles. Bone scores ranged from 0 to
      3. Biopsies from DFDBA-implanted sites revealed dead particles entrapped with
      dense connective tissue. The bone scores ranged from 0 to 1. Biopsies from sites
      implanted with hBMP/NCP revealed a combination of woven and lamellar bone with
      bone scores of 3. Five of the 6 micro screws were processed and evaluated. One
      screw was mobile at the time of removal and was not evaluated. Bone scores were
      used to compare new bone formation adjacent to the micro screws. Bone scores
      ranged from 0 to 2. A score of 0 indicated non-vital implant material in contact
      with host bone and connective tissue in contact with implant; 2 indicated vital
      bone in contact with the majority of the implant surface. Retrieved sockets with
      micro screws implanted with bovine bone (n=2) demonstrated a connective tissue
      interface between the screws and the surrounding tissues (bone score 0). The
      adjacent tissues showed dead bovine particles entrapped within fibrous tissue.
      Retrieved screws implanted with DFDBA (n=2) were surrounded by connective tissue,
      with dead bone particles enmeshed within fibrous tissue (bone score 0). The screw
      implanted with intra-oral autologous bone was primarily surrounded by vital bone
      with a connective tissue interface (bone score 1). Three implant threads were in
      contact with bone. The results of this study indicate that bovine bone, DFDBA,
      and intraoral autologous bone do not promote extraction socket healing. Sockets
      implanted with hBMP/NCP contained vital woven and lamellar bone. Xenogenic bovine
      bone and DFDBA did not contribute to bone to micro screw contacts and are not
      recommended for enhancement of vital bone to implant contacts. Intraoral
      autogenous bone also does not appear to significantly contribute to bone to
      implant contacts. Intraoral autologous bone, xenogenic bone, and DFDBA appear to
      interfere with normal extraction socket healing.

PMID- 9609371
TI  - The influence of direct composite additions for the correction of tooth form
      and/or position on periodontal health. A retrospective study.
AB  - The aim of this in vivo study was to evaluate the influence of 5- to 6-year-old
      direct composite additions on the marginal periodontal tissues. Composite
      additions were directly placed on 79 intact maxillary anterior teeth in 19
      patients (12 to 19 years) by one operator using an ultrafine midway-filled
      densified resin composite. All patients were recalled 5 to 6 years later for a
      periodontal evaluation. Plaque index, gingivitis index, and probing depth were
      measured at the buccal-approximal sites of all unilaterally restored teeth
      (n=51). An intra-individual comparison was made between the periodontal health of
      the treated versus the intact sites. The plaque index (P=0.029) and gingivitis
      index (P=0.008) were significantly higher for the treated sites compared to the
      intact sites. The difference in probing depth nearly reached the level of
      significance (P=0.059). In conclusion, 5-to 6-year-old direct composite additions
      have a negative influence on marginal periodontal health, which consisted of
      increased plaque retention, gingival inflammation, and periodontal destruction.

PMID- 9609372
TI  - Tumor necrosis factor alpha production by oral leukocytes: influence of tumor
      necrosis factor genotype.
AB  - Tumor necrosis factor alpha (TNF-alpha) is a proinflammatory cytokine that is
      thought to play a role in the pathogenesis of periodontal disease. TNF-alpha
      production is regulated by many factors, including certain alleles of TNF gene
      polymorphisms. In the present study, TNF genotypes of 3 bi-allelic polymorphisms
      were determined in 32 Caucasian patients with adult periodontitis and 32 orally
      healthy matched controls, and correlated with TNF-alpha production by oral
      polymorphonuclear leukocytes (PMN). No differences in distribution of TNF alleles
      of the -238, -308, or +252 gene polymorphisms were observed between patients and
      controls or between patients with different disease severity. However, the level
      of TNF-alpha production by oral PMN correlated with the TNF-alpha 308 genotype in
      patients with adult periodontitis, with increased production found in patients
      with the T1,2 genotype (t-test; P=0.037). When cytokine production was examined
      in patients according to disease severity, an association between the T1,2
      genotype and increased production was observed only in patients with advanced
      disease (t-test; P=0.05). These findings suggest that further studies are
      warranted to determine if the TNF genotype is a risk factor for severity of
      disease in adult periodontitis.

PMID- 9609373
TI  - Blood contamination of the aerosols produced by in vivo use of ultrasonic
      scalers.
AB  - Disease transmission and barrier techniques during dental treatment have been
      areas of recent concern in dentistry. Ultrasonic scalers are known to produce
      aerosols, and these aerosols are often produced from areas of significant disease
      activity, including bleeding. This study was performed to determine if these
      aerosols contain blood from the gingival sulcus. Forty areas consisting of two
      contiguous periodontally involved teeth (probing depth of at least 5 mm on one
      site of each tooth) were scaled subgingivally with an ultrasonic scaler for 30
      seconds. A high volume evacuator (HVE) tip was positioned 3 to 5 cm away from the
      operating site and utilized to capture the aerosols produced. The water remaining
      in and on the HVE tube was tested for occult blood by the guiac resin method.
      Gingival index, mean probing depth, presence of bleeding with scaling, and
      presence of visible blood in the HVE tip were recorded. All 40 test sites showed
      a positive result for blood in the captured aerosols despite the wide variation
      in the measured parameters. It may be concluded that subgingival scaling on
      periodontally involved teeth with ultrasonic scalers would be expected to produce
      aerosols containing blood.

PMID- 9609374
TI  - Changing number and distribution of periodontists: a continuing imbalance--1987
      1995.
AB  - A review of the 1995 and past American Dental Association (ADA) studies on the
      distribution of dentists provides information on the evolving numbers of
      periodontists. Despite an overall increase in the number of periodontists, major
      differences continue in practitioner-to-population ratios in different geographic
      areas. Suggestions include 1) efforts by the ADA and/or The Academy of
      Periodontology to draw attention to the limited numbers of periodontists in
      particular locales and states; 2) increased general efforts to educate the public
      on the need and value of periodontal services; and 3) increase in the
      profession's awareness of the growing diversity in the population of the nation
      and the need to modify and adjust its efforts to attract underserved populations
      with different familial, cultural, and educational backgrounds.

PMID- 9609375
TI  - Clinical and microbiological evaluation of a bioabsorbable and a nonresorbable
      barrier membrane in the treatment of periodontal intraosseous lesions.
AB  - Clinical and microbiological features of periodontal healing in barrier membrane
      treated sites were determined in a randomized clinical trial. The study included
      10 patients with advanced adult periodontitis and a minimum of one set of similar
      2 to 3 wall intraosseous periodontal lesions with no furcation involvement. In
      each patient, one periodontal lesion was treated with a biodegradable membrane
      and a contralateral lesion with a nonresorbable barrier membrane. Within the
      preceding 3 months of regenerative therapy, all patients received full mouth
      osseous surgery except for the sites for regeneration, were instructed in oral
      hygiene, and were prescribed systemic ciprofloxacin and metronidazole (250 mg of
      each, TID, 8 days), starting 7 days before membrane placement. At baseline and at
      6 months postsurgery, probing depth and clinical attachment level were assessed
      in each study site. The subgingival presence of suspected periodontal pathogens
      was determined by non-selective and selective culture and by DNA probe analyses,
      and of human cytomegalovirus (HCMV) and Epstein-Barr virus type 1 (EBV-1) by a
      nested-polymerase chain reaction detection method. At baseline, the barrier
      treated sites did not differ significantly in clinical and microbial parameters.
      Mean baseline probing depth was 7.8+/-1.1 mm for bioabsorbable and 7.9+/-1.3 mm
      for nonresorbable barrier-treated sites. At 6 months, sites treated with
      bioabsorbable barrier revealed 4.6+/-1.7 mm gain of clinical attachment (range: 1
      to 7 mm) and sites treated with nonresorbable barrier 4.2+/-2.0 mm (range: 1 to 8
      mm). The 11 barrier-treated sites that harbored 10% or less bacterial pathogens
      and were free of HCMV and EBV-1 averaged significantly more clinical attachment
      gain than the 9 sites that yielded more than 10% bacterial pathogens and/or test
      viruses (5.6 mm versus 3.0 mm; P=0.005). The present data suggest bioabsorbable
      and nonresorbable barriers provide similar clinical healing of 2 to 3 wall
      intraosseous periodontal lesions, emphasize the importance of controlling
      bacterial pathogens prior to and during periodontal healing, and point to the
      possible detrimental role of HCMV and EBV-1 in periodontal repair.

PMID- 9609376
TI  - Clinical comparison of cellulose and expanded polytetrafluoroethylene membranes
      in the treatment of class II furcations in mandibular molars with 6-month re
      entry.
AB  - The present study compared two barrier membranes, ePTFE and cellulose, used to
      treat Class II furcations in mandibular molars. Fifteen patients with no history
      of systemic diseases and presenting matched pair defects were selected. The
      following soft tissue measurements were taken at baseline (after the hygienic
      phase), and 6 months after surgery: gingival recession, probing depth, clinical
      attachment level, and width of keratinized tissue. At the time of membrane
      placement, and 6 months later (re-entry), the following hard tissue parameters
      were recorded: cemento-enamel junction (CEJ) to alveolar crest, CEJ to base of
      osseous defect, alveolar crest to base of osseous defect, and horizontal defect
      depth. According to the surgical protocol, the ePTFE membranes were completely
      covered by the flaps (subgingival placement), whereas the cellulose membranes
      extended 1 mm coronal to the gingival margin (supragingival placement). Healing
      was uneventful in all cases and membranes remained in place for 4 weeks. Data
      were analyzed using the Wilcoxon signed-rank test at the 5% level of
      significance. No statistically significant differences were found between the
      ePTFE and cellulose membranes, respectively (in mm): probing depth reduction
      (2.87+/-1.0 versus 3.27+/-1.1), gain in attachment level (2.53+/-1.2 versus 2.8+/
      1.3), defect fill (3.0+/-1.4 versus 4.0+/-2.3), horizontal furcation fill (2.87+/
      1.1 versus 2.93+/-1.0), alveolar crest resorption (2.4+/-10 versus 2.73+/-1.2),
      and intrabony defect fill (0.6+/-1.2 versus 1.27+/-1.7). We conclude that both
      ePTFE and cellulose membranes are effective, not showing statistical differences
      in efficacy. A larger study may be necessary to show differences in efficacy and
      adverse effects.

PMID- 9609377
TI  - Inflammatory cell population and bacterial contamination of membranes used for
      guided tissue regenerative procedures.
AB  - The purpose of this study was to determine the types of inflammatory cells and
      bacterial contamination on expanded polytetrafluoroethylene (ePTFE) membranes
      which might affect new tissue formed by guided tissue regeneration (GTR). Forty
      periodontal bony defects were treated by the flap procedure, which included the
      use of an ePTFE membrane. Twelve months after the second surgery, the defect
      sites were re-evaluated for changes in probing depth and clinical attachment
      level. The ePTFE membranes were retrieved after 4 to 6 weeks of healing and
      sectioned serially at 3 microm in a coronal-apical plane. The ePTFE membrane was
      divided into 3 portions: cervical, middle, and apical, each of which was
      subdivided into outer, central, and inner segments, providing a total of 9
      fields. Cells and bacteria were analyzed by light microscopy for their types:
      mononuclear cell, erythrocyte, fibroblast, neutrophil, plasma cell, T lymphocyte,
      B lymphocyte, macrophage, and oral bacteria. Both cells and bacteria decreased in
      number towards the apical portion and were present even in the central part. Most
      cells were mononuclear cells. Erythrocytes, fibroblasts, neutrophils, and plasma
      cells were rarely encountered. Bacteria, most of which were Gram-positive, were
      observed in almost the same number in the outer and inner parts. The results
      indicate that numerous inflammatory cells adhered to and invaded the ePTFE
      membranes accompanied by bacterial contamination and that there was a tendency
      for a negative correlation between the increment number of bacteria and the gain
      of clinical attachment level.

PMID- 9609378
TI  - Ability of commercial demineralized freeze-dried bone allograft to induce new
      bone formation is dependent on donor age but not gender.
AB  - Demineralized freeze-dried bone allografts (DFDBA) have been used extensively in
      periodontal therapy. DFDBA is used because it contains bone morphogenetic protein
      (BMP), which induces new bone formation during the healing process. Most
      commercial bone banks do not verify the presence or activity of BMP in DFDBA nor
      the ability of DFDBA to induce new bone. Recently, we showed that different bone
      bank preparations of DFDBA, even from the same bank, varied considerably in their
      ability to induce new bone, suggesting inherent differences in the quality of the
      material. Therefore, we examined whether donor age or gender contributed to the
      variability seen with these preparations. Twenty-seven batches of DFDBA from
      different donors were donated by one bone bank which had been shown previously to
      supply DFDBA that was consistently able to induce new bone formation. Each batch
      was implanted bilaterally in the thigh muscle of nude mice. After 56 days, the
      implants were excised and examined by light microscopy and histomorphometry.
      Seventy percent of the preparations tested induced new bone formation. Most of
      these preparations produced ossicles containing cortical bone surrounding bone
      marrow-like tissue. The ability to induce bone appears to be age-dependent, with
      DFDBA from older donors being less likely to have strong bone-inducing activity.
      By contrast, no difference in ability to induce new bone was noticed between male
      or female donors. The results of this study confirm that commercial preparations
      of DFDBA differ in their ability to induce new bone formation. In fact, some of
      the batches had no activity at all. The ability of DFDBA to induce new bone
      formation is suggested to be age-dependent, but not gender-dependent by our
      study. These results indicate that commercial bone banks need to verify the
      ability of DFDBA to induce new bone formation and should reconsider the
      advisability of using bone from older donors.

PMID- 9609379
TI  - Elevated salivary EGF levels stimulated by periodontal surgery.
AB  - Previous studies have shown epidermal growth factor (EGF) to be involved in oral
      wound healing as well as gastric cytoprotection. EGF functions with hormone-like
      properties to stimulate epithelial cells by binding to the EGF receptor which
      ultimately leads to proliferation via signal transduction mechanisms. Salivary
      glands are a major source of EGF The purpose of this study was to determine if
      intra-oral wounding by periodontal surgery stimulated increased salivary EGF
      levels. Salivary EGF levels were determined for 12 systemically healthy
      individuals (ages 27 to 70 years old) presurgically and postsurgically at 6, 12,
      18, 24, 30, 36, and 42 hours and 2 and 6 weeks. Three ml of unstimulated whole
      saliva was obtained at each time point to allow immunoassay quantitation. Age and
      gender matched unoperated patients served as controls. Salivary samples were
      incubated with monoclonal and polyclonal EGF antibodies in these "sandwich"
      enzyme immunoassays. Quantitation was obtained by spectrometric analysis at OD
      450 nm after addition of 200 microl of colorimetric substrate. Mean EGF levels
      ranged from 2441 pg/ml presurgically to 3349 pg/ml at 18 hours postsurgically and
      1207 pg/ml at 6 weeks postsurgically. Repeated measures analysis of variance
      indicated statistically significant differences in 18 hours postsurgical salivary
      EGF levels when compared to controls and to postsurgical levels from 36 hours
      forward (P < 0.01). A second smaller rise in EGF was detected at 30 hours. These
      results suggest a transient increase in salivary EGF levels in response to intra
      oral wounding.

PMID- 9609380
TI  - A histological study on tissue responses to titanium implantation in rat maxilla:
      the process of epithelial regeneration and bone reaction.
AB  - The present study aimed to establish a titanium implantation model using rat
      maxillae as well as demonstrate the chronological tissue responses to
      implantation. Pure titanium implants were inserted in the upper first molar
      extraction sites of Wistar rats 1 month after tooth extraction. The animals were
      sacrificed at 1 to 30 days postimplantation, and prepared tissue specimens were
      processed for light microscopy. The removal of implants from tissue blocks was
      done using 2 methods: mechanical removal or a cryofracture technique. In the
      early stages, peri-implant tissues showed severe damage to the oral epithelium
      and collagen bundles with significant inflammatory cell infiltration. The peri
      implant epithelium grew apically along the implant by 10 days postimplantation,
      and regenerated to show a similar feature of junctional epithelium seen in normal
      rats at 15 days postimplantation, at which time no signs of inflammation were
      observed. The regenerated collagen bundles in the connective tissue were arranged
      circumferentially to the implants in the horizontal sections. New bone formation
      first appeared around the implants at 5 days postimplantation, covering the
      entire perimeter of implants by 30 days postimplantation. Scanning electron
      microscopic observations of the surface texture of the removed implants suggest
      the probability of an adhesive mechanism between the implants and the peri
      implant epithelium and/or the alveolar bone. These findings indicate that this
      experimental model is useful for detailed analysis of peri-implant tissue because
      of its easy implantation procedure.

PMID- 9609381
TI  - Association of oral spirochetes from periodontally healthy sites with development
      of gingivitis.
AB  - The purpose of this investigation was to determine whether the presence of
      selected disease-associated bacteria in health-associated plaque correlated with
      future gingivitis. Sites of periodontal health were identified in 65 adults. Six
      months later (recall 1) plaque was collected from sites that remained in
      periodontal health, and 5 species of specific bacteria and pathogen-related oral
      spirochetes were detected using monoclonal antibodies in a microscopic assay.
      Members of the spirochete morphogroup were also identified by phase contrast
      microscopy. The relationship between site-specific detection of bacteria at
      recall 1 and development of gingivitis at recall 2 or 3 was evaluated by means of
      logistic regression using generalized estimating equations, from which odds
      ratios (OR) were estimated. Significance was conservatively defined as OR > 2.0
      and P < 0.05. We found that 488 of 1,424 healthy sites developed gingivitis over
      the 12-month interval between recall 1 and 3. Only the spirochete morphogroup (OR
      =2.04; P=0.002) was significantly associated with the transition from health to
      gingivitis. The association of Treponema socranskii with future gingivitis was
      higher than expected (OR=2.27), but the relationship was not statistically
      significant (P=0.163). Campylobacter rectus, Eikenella corrodens, Porphyromonas
      gingivalis, and pathogen-related oral spirochetes did not correlate well with
      gingivitis (OR < 2.0). Health-associated plaque from 5 sites contained Treponema
      denticola, and all 5 sites progressed to gingivitis. An OR could not be
      calculated because T. denticola was not detected in health-associated plaque from
      stable healthy sites. These findings indicated that the presence of T. denticola
      and unidentified spirochetes in health-associated plaque was associated with
      increased susceptibility to gingival inflammation. Future studies assessing a
      larger panel of dental plaque microorganisms, with shorter intervals between
      baseline and follow-up assessment, are necessary to more fully evaluate the
      association between detection of specific organisms at healthy sites and risk for
      gingivitis.

PMID- 9609382
TI  - Supportive periodontal therapy (SPT).
AB  - The purpose of this paper is to provide a general overview of the role of
      supportive periodontal therapy in the treatment of periodontal diseases. Reliance
      on this position paper in patient management will not guarantee a successful
      outcome, as periodontal diseases typically involve numerous and complex causes
      and symptoms. Ultimately, decisions regarding the diagnosis, treatment, and
      management of disease, as well as subsequent preventive therapy, must be made by
      the treating practitioner based on the specific circumstances presented by that
      patient.

PMID- 9609383
TI  - Toxicity of fotemustine in rat hepatocytes and mechanism-based protection against
      it.
AB  - Fotemustine is a relatively novel DNA-alkylating 2-chloroethyl-substituted N
      nitrosourea (CENU) drug, clinically used for the treatment of disseminated
      malignant melanoma in different visceral and non-visceral tissues.
      Thrombocytopenia has been observed in patients treated with fotemustine and liver
      and renal toxicities as well. In this study, firstly the metabolism of
      fotemustine was investigated in vitro and secondly the undesired cytotoxicity of
      fotemustine as well as different ways of protection against it. In rat
      hepatocytes, chosen as a model system, fotemustine was shown to cause lactate
      dehydrogenase (LDH) leakage, glutathione (GSH) depletion, GSSG-formation and
      lipid peroxidation (LPO). A reactive metabolite, DEP-isocyanate, is most likely
      responsible for these undesired cytotoxic effects. Based on the observed
      cytotoxicity mechanisms, chemoprotection with several sulfhydryl-containing
      nucleophiles and antioxidants was investigated. The sulfhydryl nucleophiles; GSH,
      N-acetyl-L-cysteine (NAC) and glutathione isopropylester (GSH-IP) protected
      almost completely against fotemustine-induced LDH-leakage and LPO. NAC and GSH
      protected partly against fotemustine-induced GSH-depletion. The antioxidant,
      vitamin E protected completely against fotemustine-induced LPO, but only partly
      against fotemustine-induced LDH-leakage and not against GSH-depletion. Ebselen, a
      peroxidase-mimetic organoselenium compound, did not show protective effects
      against the cytotoxicity of fotemustine, possibly because GSH is required for the
      bioactivation of ebselen. It is concluded that co-administration of sulfhydryl
      nucleophiles, in particular NAC and GSH-IP, possibly in combination with
      antioxidants, such as vitamin E, are effective against the toxicity of
      fotemustine in vitro. It might, therefore, be worthwhile to investigate the
      cytoprotective potency of these agents against undesired toxicities of
      fotemustine in vivo as well.

PMID- 9609384
TI  - Involvement of protein tyrosine phosphorylation in the effect of green tea
      polyphenols on Ehrlich ascites tumor cells in vitro.
AB  - Green tea extract and its polyphenolic components have been found to possess
      anticarcinogenic, antimutagenic, antihypertensive and antihepatotoxic effects,
      and several mechanisms have been proposed for these effects. In this study, the
      effects of five tea polyphenols, (-)-epigallocatechin-3-gallate (EGCG), (-)
      epigallocatechin (EGC), (-) epicatechin-3-gallate (ECG), ( -) epicatechin (EC)
      and (+)-catechin (C), were examined on the viability of Ehrlich ascites tumor
      cells in vitro and a possible relationship with tyrosine phosphorylation was
      determined. Proteins extracted from the cells treated with the tea polyphenols
      were separated by SDS-PAGE, and tyrosine-phosphorylated proteins were detected by
      immunoblotting with anti-phosphotyrosine antibody and the extent of
      phosphorylation determined. EGC (100 microM) caused a significant decrease in
      cell viability to 4.1 +/- 0.2% of the control value, and this correlated with a
      stimulation of protein tyrosine kinase (PTK) activity. EGCG (100 microM) also
      caused a slight decrease in cell viability (approximately 70% of the control
      value) but this and the other polyphenols, which had no effect on cell viability
      likewise, had no effect on tyrosine phosphorylation. Tyrosine phosphorylations of
      42 and 45 kDa proteins were also observed for EGC. Further evaluation of the
      effect of EGC showed that the activity of ornithine decarboxylase (ODC), a key
      enzyme in polyamine biosynthesis in cells, decreased significantly as well. A
      significant correlation has therefore been observed between a cellular event,
      namely, a reduction in the viability of Ehrlich ascites tumor cells and an
      association with a tyrosine phosphorylation of 42 and 45 kDa proteins by the
      polyphenol EGC.

PMID- 9609385
TI  - Evidence for the DNA binding and adduct formation of estrone and 17beta-estradiol
      after dimethyldioxirane activation.
AB  - Estrogens, used widely from hormone replacement therapy to cancer treatment, are
      themselves carcinogenic, causing uterine and breast cancers. However, the
      mechanism of their carcinogenic action is still not known. Recently, we found
      that estrone (E1) and 17beta-estradiol (E2) could be activated by the versatile
      epoxide-forming oxidant dimethyldioxirane (DMDO), resulting in the inhibition of
      rat liver nuclear and nucleolar RNA synthesis in a dose-dependent manner in
      vitro. Since epoxidation is often required for the activation of chemical
      carcinogens, we proposed that estrogen epoxidation is the underlying mechanism
      for the initiation of estrogen carcinogenesis (Carcinogenesis 17 (1996) 1957
      1961). It is known that initiation requires the binding of a carcinogen to DNA
      with the formation of DNA adducts. One of the critical tests of our hypothesis is
      therefore to determine whether E1 and E2 after activation are able to bind DNA.
      This paper reports that after DMDO activation, [3H]E1 and [3H]E2 were able to
      bind to both A-T and G-C containing DNAs. Furthermore. the formation of E1-DNA
      and E2-DNA adducts was detected by 32P-postlabeling analysis.

PMID- 9609386
TI  - The glutathione dependence of inorganic sulfate formation from L- or D-cysteine
      in isolated rat hepatocytes.
AB  - The GSH dependence of the metabolic pathways involved in the conversion of
      cysteine to sulfate in intact cells has been investigated. It was found that
      hepatocyte-catalysed sulfate formation from added L-cysteine did not occur if
      hepatocyte GSH was depleted beforehand, but was restored when GSH levels
      recovered. Furthermore, sulfate formation did not recover in GSH-depleted
      hepatocytes if GSH synthesis was prevented with buthionine sulfoximine.
      Thiosulfate formation was, however, markedly enhanced in GSH-depleted
      hepatocytes. These results suggest that thiosulfate is an intermediate in the
      formation of inorganic sulfate from L-cysteine and that GSH was required for the
      conversion of thiosulfate to inorganic sulfate. Much less sulfate was formed if
      the cysteine was replaced with cysteinesulfinate. Furthermore, sulfate formation
      from L-cysteine was markedly inhibited by the addition of the transaminase
      inhibitor DL-cycloserine or the gamma-cystathionase inhibitor DL
      propargylglycine. The major routes of sulfate formation from L-cysteine therefore
      seems to involve pathways that do not involve L-cysteinesulfinate. Similar
      amounts of sulfate were formed from D-cysteine as L-cysteine. Thiosulfate instead
      of sulfate was also formed in GSH-depleted hepatocytes. However, sulfate
      formation from D-cysteine differed from L-cysteine in that it was inhibited by
      the D-aminoacid oxidase inhibitor sodium benzoate and was not affected by
      transaminase or gamma-cystathionase inhibitors. These results suggest that
      thiosulfate is an intermediate in sulfate formation from D-cysteine and involves
      the oxidation of D-cysteine by D-amino acid oxidase to form beta
      mercaptopyruvate.

PMID- 9609387
TI  - Action of antitumoral platinum complexes on in vitro platelet functions.
AB  - This report presents a comparison of the effects of cis- and trans
      diamminedichloroplatinum complexes on in vitro platelet functions. Pretreatment
      of platelets with cis-platinum (cisplatin) induced a slow, dose-dependent (0.1
      0.45 mM), increase in the cytosolic Ca2+ concentration, pleckstrin (47 kDa)
      phosphorylation and serotonin secretion, as well as a slight shape modification
      with emission of a few pseudopodia. All these effects were remarkably increased
      in platelets exposed to trans-platinum (transplatin). The rise in cytosolic Ca2+
      concentration and serotonin secretion evoked by stimulation of platelets with
      thrombin were not significantly influenced by cellular exposure to cis-platinum,
      whereas they were enhanced and inhibited, respectively, by exposure to trans
      platinum. Trans-platinum also inhibited thrombin-promoted platelet aggregation to
      a greater extent than the cis-isomer. While the viscosity of platelet rich-plasma
      tended to decrease in the presence of cis-platinum, it tended to increase in the
      presence of trans-platinum. Taken together, these results indicate that the
      effects on platelet functions of the efficacious antitumor complex cis-platinum
      is rather different from that of the inactive complex trans-platinum. Therefore,
      the in vitro tests of platelet functions employed in this study might provide an
      index of antitumor drug toxicity and serve as a preliminary indicator of
      therapeutic efficacy.

PMID- 9609388
TI  - Analysis of micronuclei and DNA single-strand breaks in mouse splenocytes and
      peripheral lymphocytes after oral administration of tetramethylthiuram disulfide
      (thiram).
AB  - The fungicide thiram (tetramethylthiuram disulfide, TMTD) was administered by
      repeated oral intubations to groups of male B6C3F1 mice at 100, 300 and 900 mg/kg
      body weight for 4 consecutive days, or at 300 mg/kg for 8 and 12 days. 24 hr
      after the last treatment animals were killed, and splenocyte cultures were set up
      for the analysis of micronuclei by the cytokinesis-block method. DNA single
      strand breaks (ssb) and alkali labile sites were also analysed by the single cell
      gel electrophoresis (Comet) assay in splenocytes and lymphocytes of animals
      receiving the 8- and 12-day treatments. Parallel experiments with human
      peripheral lymphocytes were carried out to assess the ability of thiram to induce
      micronuclei and DNA ssb and alkaline labile sites under in vitro conditions. No
      significant increase of micronucleated splenocytes was observed in treated
      animals, despite some evidence of treatment-related cellular toxicity. A
      borderline excess of DNA damage was suggested by the Comet assay on circulating
      lymphocytes, whereas negative results were obtained with splenocytes. In vitro,
      positive results with both genetic end points were obtained in assays with human
      lymphocytes in the dose ranges 0.5-24 microg/ml and 0.1-8 microg/ml for
      micronucleus and Comet assays, respectively. These results suggest that thiram,
      despite its established genotoxicity in vitro, is devoid of appreciable
      clastogenic and/or aneugenic activity in vivo after oral administration to mice
      at the maximum tolerated dose.

PMID- 9609389
TI  - Subchronic inhalation toxicity study of 2-ethylhexanol vapour in rats.
AB  - A 90-day subchronic inhalation toxicity study was performed on Wistar rats in
      accordance to OECD testing guidelines to evaluate the toxicological profile of 2
      ethylhexanol, potential target organs, and a no-observable-adverse-effect-level
      (NOAEL). 10 males and 10 females per group were exposed to 2-ethylhexanol vapours
      at concentrations of 15, 40 and 120 ppm (the latter corresponding to the vapour
      saturation at 20 degrees C) 6 hours/day for 90 days. The respective controls
      inhaled clean air under the same conditions. No substance-related adverse effects
      were observed for body weight, body weight gain, mortality, organ weights,
      clinical biochemistry and haematological parameters including clotting time.
      Cyanide-insensitive palmitoyl-CoA oxidation, a marker for peroxisome
      proliferation, was found elevated in a subchronic study in Fischer 344 rats after
      gavage application of 500 mg/kg but not under the conditions of this 90-day
      subchronic inhalation study. There were no findings related to the treatment with
      2-ethylhexanol either at necropsy or at histological examination. The highest
      concentration tested under these conditions (120 ppm) was found to be the NOAEL
      for male and female rats.

PMID- 9609390
TI  - Chemical and biological studies of a new cigarette that primarily heats tobacco.
      Part 1. Chemical composition of mainstream smoke.
AB  - A new-technology cigarette has been developed. While the new cigarette burns some
      tobacco, it does not use tobacco as the fuel to sustain combustion and provide
      heat to the cigarette. Rather, the new cigarette primarily heats tobacco thereby
      reducing products of smoke formation mechanisms such as tobacco combustion,
      tobacco pyrolysis and pyrosynthesis. The mainstream smoke composition from a
      cigarette based on the new design (TOB-HT) has been characterized in comparative
      chemical testing with two reference cigarettes using the FTC puffing regimen.
      Thermal properties, UV absorption characteristics, elemental composition and
      materials balance studies all suggest a simplified smoke aerosol. Twenty-five
      smoke constituents ("target compounds") identified by the scientific community as
      compounds that may contribute to the diseases statistically associated with
      smoking have also been measured. Mainstream smoke concentrations of most target
      compounds are significantly lower with the TOB-HT cigarette when compared with
      reference cigarettes in the ultra-light "tar" and light "tar" categories. Taken
      together, chemical analysis results suggest simplified TOB-HT smoke chemistry
      with marked reductions in specific chemicals reported to be biologically active.

PMID- 9609391
TI  - Chemical and biological studies of a new cigarette that primarily heats tobacco.
      Part 2. In vitro toxicology of mainstream smoke condensate.
AB  - The genotoxic and cytotoxic potential of mainstream cigarette smoke condensate
      (CSC) from a new cigarette that primarily heats tobacco (TOB-HT) was compared
      with that of CSC from a Kentucky reference low "tar" cigarette (1R4F)
      representative of the current US cigarette market, and Kentucky Reference 1R5F,
      representative of ultra-low "tar" cigarettes on the US market. TOB-HT was
      evaluated at concentrations which induced concentration-dependent positive
      responses with 1R4F and 1R5F in an in vitro toxicology test battery which
      included sister chromatid exchange, chromosome aberration, and neutral red
      cytotoxicity assays in CHO cells, and the Ames bacterial mutagenicity assay. CSC
      from 1R4F and 1R5F was positive in the Ames assay with Salmonella typhimurium
      strains TA98, TA100, TA1538 and TA1537, and negative with TA1535, while CSC from
      TOB-HT was negative in all five strains. CSC from 1R4F and 1R5F cigarettes was
      positive in sister chromatid exchange (SCE), chromosome aberration (CA) and
      neutral red cytotoxicity assays, while CSC from the TOB-HT cigarette yielded
      negative results in all the above endpoints. These data indicate that in these
      assays the genotoxic and cytotoxic potential of CSC from the new cigarette that
      primarily heats tobacco is significantly less than CSC from Kentucky reference
      1R4F and 1R5F cigarettes, which are representative of cigarettes currently sold
      in the US.

PMID- 9609392
TI  - Chemical and biological studies of a new cigarette that primarily heats tobacco.
      Part 3. In vitro toxicity of whole smoke.
AB  - Mainstream smoke from Kentucky reference low "tar" (1R4F) and ultra-low "tar"
      (1R5F) cigarettes and a test cigarette (TOB-HT), that primarily heats tobacco,
      was compared for cytotoxic and genotoxic potential using cellular smoke exposure
      technology (CSET). CSET includes a computer controlled 30-port AMESA/Battelle
      Geneva smoke generator which exposes cultured mammalian Chinese hamster ovary
      cells (CHO) to whole smoke. Cytotoxicity was assessed using the neutral red assay
      and genotoxicity was assessed using the sister chromatid exchange (SCE) assay.
      Compared on a per cigarette basis, mainstream smoke from 1R5F and the TOB-HT
      cigarette was significantly less cytotoxic and genotoxic than the smoke from the
      1R4F cigarette. The cytotoxic and genotoxic activity of smoke from the TOB-HT
      cigarettes was slightly greater than the smoke from the ultra-low "tar" Kentucky
      1R5F reference cigarettes. In conclusion, in these assays mainstream whole smoke
      of the TOB-HT cigarette had slightly greater cytotoxic and genotoxic potential
      compared with an ultra-low "tar" 1R5F Kentucky reference cigarette and
      significantly less activity compared with the whole mainstream smoke from a low
      "tar" 1R4F Kentucky reference cigarette, representative of the US market average
      cigarette for FTC yields of "tar", CO and nicotine.

PMID- 9609393
TI  - Selective induction of type 2 cytokines following topical exposure of mice to
      platinum salts.
AB  - Repeated topical exposure of BALB/c strain mice to organic chemical respiratory
      allergens, such as trimellitic anhydride (TMA), or contact allergens such as 2,4
      dinitrochlorobenzene (DNCB), provokes characteristic cytokine secretion profiles
      consistent with the divergent activation of discrete T cell subpopulations. Under
      such conditions, lymph node cells (LNC) isolated from animals exposed to TMA
      elaborated comparatively large amounts of the type 2 cytokines interleukin 10 (IL
      10) and mitogen-inducible interleukin 4 (IL-4), but only low levels of the type 1
      product interferon gamma (IFN-gamma). In contrast, DNCB-activated LNC displayed
      the converse (type 1) cytokine secretion profile. We have now examined cytokine
      production induced by topical application to mice of respiratory sensitizing
      platinum salts; ammonium tetrachloroplatinite II, ammonium hexachloroplatinate IV
      and cis-dichlorodiammine platinum II. Metal salts were dissolved in dimethyl
      sulfoxide (DMSO). Cytokine secretion profiles were compared with those elicited
      following concurrent exposure to TMA or DNCB or to the vehicle acetone:olive oil
      (AOO) alone. All three platinum salts and TMA stimulated vigorous IL-4 and IL-10
      production compared with DNCB-activated LNC; vehicle-stimulated LNC failed to
      elaborate detectable levels of either cytokine. However, DNCB and the DMSO
      vehicle provoked substantial IFN-gamma expression, whereas exposure to AOO
      vehicle resulted in a considerably weaker IFN-gamma response. Levels of this
      cytokine induced by treatment with respiratory allergens were, in the majority of
      cases, substantially lower than those observed with the relevant vehicle. Indeed,
      an inverse dose-response relationship for IFN-gamma expression was exhibited by
      all three platinum salts, suggestive of the elaboration by platinum salt
      activated LNC of an inhibitory factor or factors for IFN-gamma. These data
      suggest that it may be possible to identify those metal salts with respiratory
      sensitizing potential as a function of induced type 2 cytokine secretion
      patterns.

PMID- 9609394
TI  - A comparison of low volume, Draize and in vitro eye irritation test data. III.
      Surfactant-based formulations.
AB  - The third phase in a series of investigations of the relationship between low
      volume eye test (LVET) data, Draize eye irritation test data, and comparable data
      from in vitro assay protocols is presented. These investigations utilize Draize
      eye test and in vitro endpoint data generated previously as part of the CTFA
      Evaluation of Alternatives Program. LVET data were generated de novo using the
      same 25 representative surfactant-based personal-care formulations. In general,
      these formulations were minimally to moderately irritating. The linear
      correlation between maximum average score as determined by the Draize test (MAS)
      and the LVET (LVET-MAS) was 0.87; LVET-MAS values were typically about 30% lower
      then corresponding MAS values. Comparison of in vitro assay performance with that
      of the LVET was determined by statistical analysis of the relationship between
      LVET-MAS and in vitro endpoint. Regression modelling was the primary means of
      enabling such a comparison, the objective being to predict LVET-MAS for a given
      test material (and to place upper and lower prediction bounds on the range in
      which the LVET-MAS is anticipated to fall with high probability) based on
      observation of an in vitro score for that material. The degree of 95% confidence
      in prediction is quantified in terms of the relative widths of prediction
      intervals constructed about the fitted regression curves. Twenty in vitro
      endpoints were shown to have the greatest agreement with the LVET (these
      endpoints included those with low discordance rates relative to the Draize test)
      and were therefore selected for regression modelling. Although prediction
      interval widths tended to be narrower when predicting LVET-MAS compared with
      predicting MAS, the confidence with which the selected in vitro endpoints
      predicted both LVET-MAS and MAS for surfactant-based formulations was greatest
      when values were close to the lower or upper limits of the observed irritation
      range (i.e. 95% prediction interval widths were most narrow in these areas).
      Overall precision of LVET-MAS prediction for surfactant-based formulations was
      similar to that previously reported for hydroalcoholic formulations and
      considerably better than was reported for oil/water emulsions.

PMID- 9609395
TI  - Skin irritation potential of mixed surfactant systems.
AB  - Virtually all current detergent formulations contain mixtures of surfactants. Our
      experience and test data on these formulations, which is in agreement with that
      of many others, has shown that in use the formulations exhibit lower acute
      irritation potential than predicted by simple summation of the irritation
      potential of the individual actives. Using the criteria of the Dangerous
      Preparations Directive (EC Directive 88/379/EEC), many of these formulations
      classify as irritant in the neat state, with consequent labelling requirements.
      Such classification is based on addition of irritant components giving a total
      concentration which exceeds a nominal threshold. In this study, mixtures of
      surfactants were tested by application to a panel of 31 human volunteers for up
      to 4 hr, using the technique established for the assessment of acute skin
      irritation potential. The positive control, sodium dodecyl sulfate (SDS) at 20%
      concentration, gave an 84% positive response. Dimethyl dodecyl amido betaine
      (DDAB) at the same concentration gave a 94% response. However, a combination of
      20% of each of these surfactants in the same panellists gave a response of only
      44%--a significant reduction in the irritation potential. A further test
      conducted with a mixture of 10% SDS and 10% DDAB in a second panel gave a 31%
      positive response compared with a 94% positive response to the 20% SDS control in
      that panel. These results clearly demonstrate that the acute irritation potential
      of mixed surfactants cannot be predicted by simple summation of the irritation
      potential of the component substances. Initial results of the mechanistic
      investigation indicate that the reduced irritation induced by the mixed
      surfactant systems correlates with a reduced critical micelle concentration
      (CMC). However, the reduced CMC itself seems not to be responsible for the
      lowered irritation, since these experiments were conducted at concentrations well
      above the CMC. It is proposed that the critical event leading to skin irritation
      is binding to skin protein and that in mixed surfactant systems, the individual
      surfactants exhibit less affinity for this protein.

PMID- 9609396
TI  - Effect of taurine on toxicity of copper in rats.
AB  - An attempt was made to study the effect of taurine on the toxicity of copper in
      male Wistar rats. The rats were divided into eight groups and fed different diets
      with or without supplement of 5% taurine and 150-600 ppm copper for 2 months. It
      was found that the levels of copper and malondialdehyde (MDA) in the liver, and
      the activities of aspartate transaminase (AST) and alanine transaminase (ALT) in
      the plasma of rats were increased with the increasing dose of copper. However,
      the levels of copper and MDA, and the enzyme activities of AST and ALT in the
      rats fed with supplement of taurine were significantly lower than in the rats fed
      without supplement of taurine. The level of copper in the faeces of rats treated
      with taurine and copper was higher than that of rats treated with copper alone.
      It indicated that taurine might play a role in reducing the toxic effect of
      copper in rats.

PMID- 9609397
TI  - Balkan endemic nephropathy, the haematopoietic system and the environmental
      connection.
AB  - We previously reported the detection of an increased subpopulation of cytotoxic T
      lymphocytes in patients with Balkan (endemic) nephropathy (BEN) and in area
      controls (individuals free of clinical syndrome but born in a BEN endemic area
      and having a family history of BEN). Extending the flow-cytometric analyses to
      other populations of peripheral blood leucocytes, we found a decrease in the
      proportion of B lymphocyte subset and an increased proportion of eosinophils in
      BEN patients and in area controls. Although these numerical alterations cannot be
      categorically linked to the aetiopathogeny of the disease, it is presumed that
      they can be induced by the same factor(s) causing the kidney damage, through a
      direct haemato- and lymphotoxic effect.

PMID- 9609398
TI  - The intermediate filament protein peripherin is a marker for cerebellar climbing
      fibres.
AB  - Immunocytochemical staining with antibodies to the class III intermediate
      filament protein peripherin reveals discrete subpopulations of neurons and nerve
      fibres throughout the rat central nervous system. Some of these fibres enter the
      cerebellar granular and molecular layers. Here we use light and electron
      microscopic immunocytochemistry and confocal fluorescence microscopy to identify
      the peripherin positive fibres in the molecular layer of the cerebella of various
      mammals. (1) The peripherin positive fibres in the molecular layer have
      morphological attributes of climbing fibres, and peripherin positive fibres are
      also detected in the olivo-cerebellar tract. Furthermore peripherin positive
      neurons can be seen in the inferior olive, from which climbing fibres originate.
      (2) The peripherin positive molecular layer fibres rapidly degenerate in rats
      treated with 3-acetylpyridine (3-AP), a reagent which destroys neurons in the
      inferior olive, and the time course of degeneration of these mirrors that
      previously described for 3-AP induced destruction of climbing fibres. (3)
      Cerebella of other mammal species tested (mouse, rabbit, pig, cow and human)
      revealed a similar peripherin staining pattern in the cerebellum, including
      fibres in the molecular layer with the morphology of climbing fibres. (4) We also
      noted peripherin positive spinocerebellar and vestibulocerebellar mossy fibres in
      the cerebellar granular layer of folia known to receive these inputs. (5) A
      subset of perivascular nerve fibres are also peripherin positive. These results
      show that peripherin is a useful marker for mammalian cerebellar climbing fibres,
      and that a subset of morphologically distinct cerebellar mossy fibres are also
      peripherin positive.

PMID- 9609399
TI  - Redistribution of Schwann cells at the developing PNS-CNS borderline. An
      ultrastructural and autoradiographic study on the S1 dorsal root of the cat.
AB  - In order to test our hypothesis that myelin-forming Schwann cells early during
      development, after having been eliminated from their parent axons, colonize
      neighbouring unmyelinated axons, we studied the distribution of Schwann cells at
      the PNS-CNS border in the feline S1 dorsal spinal root during pre- and postnatal
      development using electron microscopy and autoradiography. Myelination of axons
      peripheral to the PNS-CNS border began about 1.5 weeks before birth. The adult
      distribution of one-third myelinated and two-thirds unmyelinated axons was noted
      3 weeks after birth. Analysis based on to-scale reconstructions of axon and
      Schwann cell samples from the first 6 postnatal weeks gave the following results.
      (1) CNS tissue appeared in the proximal part of the root around birth and
      expanded peripherally during the first three postnatal weeks. (2) The number of
      Schwann cells associated with myelinated axons decreased. (3) The number of
      Schwann cells associated with unmyelinated axons increased. (4) The mitotic
      activity of the Schwann cells was low at birth and nil after the first postnatal
      weak. (5) Apoptotic cell units were virtually absent. (6) Aberrant Schwann cells,
      i.e. short and very short Schwann cells with distorted and degenerating myelin
      sheaths, were common. (7) The endoneurial space contained numerous Schwannoid
      cells i.e. solitary cells surrounded by a basal lamina. (8) Cytoplasmic contacts
      between unmyelinated axons and aberrant Schwann cells or Schwannoid cells were
      observed. We take these results to support our hypothesis.

PMID- 9609400
TI  - Paranodal Schwann cell mitochondria in spinal roots of the cat. An
      ultrastructural morphometric analysis.
AB  - We have calculated the number of paranodal Schwann cell mitochondria in adult
      feline ventral and dorsal lumbar spinal roots using ultrastructural serial
      section analysis. Distinct accumulations of paranodal mitochondria were noted in
      nerve fibres more than 4-5 microm in diameter. The calculated number of paranodal
      mitochondria increased linearly with fibre diameter from a few hundred up to
      20,000-30,000 per node. A linear increase in the number of paranodal mitochondria
      per node also appeared as a function of nodal variables such as 'nodal axon
      membrane area', 'nodal Schwann cell membrane area', and 'node gap extracellular
      volume'. In large fibres (D = 15-18 microm), a calculated number of about 20,000
      paranodal Schwann cell mitochondria were accumulated at each node of Ranvier and
      related to nodal axon membrane area of about 20 microm2. Our calculations
      indicate that, on the average, 1000 paranodal Schwann cell mitochondria with a
      total volume of 6.7 microm3, a total outer membrane area of 250 microm2 and a
      total inner membrane area of 580 microm2 projected to each microm2 of the nodal
      axon membrane via the nodal Schwann cell brush border.

PMID- 9609401
TI  - The glio-toxic mechanism of alpha-aminoadipic acid on cultured astrocytes.
AB  - The mechanism of action of the glutamate analogue alpha-aminoadipic (AAA) acid
      was investigated in terms of its toxicity to cultured astrocytes. AAA was more
      toxic to type 1 astrocytes than type 2 astrocytes. Also the higher toxicity of
      the L-isomer as compared to the D-isomer was seen on type 1 astrocytes but not
      type 2. The toxicity of AAA can be reduced by co-culture of type 1 astrocytes
      with microglia. This inhibition may be due to glutamate release by microglia. No
      such effect is seen for type 2 astrocytes. The major uptake route for AAA by type
      1 astrocytes is through the sodium dependent glutamate port. Both isomers of AAA
      are toxic to dividing astrocytes. The D-isomer appears to be toxic only for
      mitotic cells. The mechanism of this toxicity is protein synthesis dependent. It
      is suggested that AAA is toxic to mitotic astrocytes by interference with protein
      synthesis needed for cell division. D-AAA as opposed to L-AAA may prove a
      valuable tool for investigation of astrocyte proliferation in development and
      disease.

PMID- 9609402
TI  - Microtubule dynamics in a cytosolic extract of fetal rat brain.
AB  - Brain microtubule dynamics were studied by video-enhanced differential
      interference contrast microscopy in a cytosolic extract from fetal rat brain,
      prepared under conditions designed to produce minimal alterations in microtubule
      stability. With urchin sperm axoneme fragments as nucleation seeds, the extract
      was shown to support cellular-like microtubule dynamics. Microtubules elongated
      from one end of the axonemes, and did not spontaneously self-assemble in the
      absence of axonemes. The following microtubule kinetic parameters were measured
      in the extract: velocity of elongation (8.1 mm/min), velocity of rapid shortening
      (5.8 mm/min), catastrophe frequency (0.17 min(-1)), and rescue frequency (1 min(
      1)). These parameters were in close agreement with reported values for growth
      cones of living neurons. Microtubule properties in the fetal brain extract were
      shown to be affected by agents with known effects on the cytoskeleton. pp60c-src,
      a tyrosine kinase important in cell adhesion molecule-dependent axon growth,
      caused small increases in the frequency of microtubule catastrophe (0.31 min(-1))
      and rescue (2 min(-1)) without changing the velocities of elongation or rapid
      shortening. Although pp60c-src phosphorylated purified porcine brain tubulin in
      vitro, it did not elicit significant changes in its polymerization properties,
      suggesting that other cytoskeletal proteins in the brain extract are involved in
      modulating microtubule dynamics. The cytosolic extract of fetal rat brain
      provides a useful system for studying regulation of microtubule assembly in
      neuronal growth cones.

PMID- 9609403
TI  - Development of glia and blood vessels in the internal capsule of rats.
AB  - We have explored two aspects of internal capsule development that have not been
      described previously, namely, the development of glia and of blood vessels. To
      these ends, we used antibodies to glial fibrillary acidic protein (GFAP) and to
      vimentin (to identify astrocytes and to radial glia) and Griffonia simplicifolia
      (lectin; to identify microglia and blood vessels). Further, we made intracardiac
      injections of Evans Blue to examine the permeability of this dye in the vessels
      of the internal capsule during neonatal development. Our results show that large
      numbers of radial glia, astrocytes and microglia are not labelled with these
      markers in the white matter of the internal capsule until about birth; very few
      are labelled earlier, during the critical stages of corticofugal and corticopetal
      axonal ingrowth (E15-E20). The large glial labelling in the internal capsule at
      birth is accompanied by a dense vascular innervation of the capsule; as with the
      glia, very few labelled patent vessels are seen earlier. After intracardiac
      injections of Evans Blue, we find that the blood vessels of the internal capsule
      are not particularly permeable to Evans Blue. At each age examined (P0, P5, P15),
      blood vessels are outlined very clearly and there is no diffuse haze of
      fluorescence within the extracellular space, which is indicative of a leaky
      vessel. There are three striking differences between the glial environment of the
      internal capsule and that of the adjacent thalamus. First, the internal capsule
      is never rich with radial glial fibres (vimentin- and GFAP-immunoreactive) during
      development (except at P0), whereas the thalamus has many radial fibres from very
      early development (E15-E17). Second, astrocytes (vimentin- and GFAP
      immunoreactive) first become apparent in the internal capsule (E20-P0) well
      before they do in the thalamus (P15). Third, the internal capsule houses a large
      transient population of amoeboid microglia (P0-P22), whereas the thalamus does
      not; only ramified microglia are seen in the thalamus. In summary, our results
      indicate that all three types of glia in the internal capsule are associated
      closely with the vasculature, suggesting they may play a role in the development
      of the blood-brain barrier among the vessels in this white matter region of the
      forebrain.

PMID- 9609404
TI  - Fixed-dose combination therapy: panacea or poison?

PMID- 9609406
TI  - Bronchoalveolar lavage fluid characteristics of early intermediate and late
      phases of ARDS. Alterations in leukocytes, proteins, PAF and surfactant
      components.
AB  - OBJECTIVE: To determine the concentration of proteins and phospholipids, markers
      of inflammatory reaction such as platelet-activating factor (PAF), and cell
      alterations in bronchoalveolar lavage (BAL) fluid during the evolution of the
      acute respiratory distress syndrome (ARDS). DESIGN: Prospective controlled study.
      SETTING: 14-bed medical-surgical intensive care unit in a 750-bed university
      teaching hospital. PATIENTS: 19 mechanically ventilated patients, 9 patients with
      ARDS and 10 patients without cardiopulmonary disease (controls), were eligible
      for this study. INTERVENTIONS: BAL was performed during the early, intermediate,
      and late phases of ARDS. MEASUREMENTS AND RESULTS: Total phospholipids and
      individual phospholipid classes of the surfactant, proteins, PAF, and cells were
      measured. High levels of PAF, an increase in neutrophils and proteins, and
      quantitative as well as qualitative alterations in phospholipids in BAL fluid
      were observed in ARDS patients compared to the control group. PAF, proteins, and
      neutrophils were higher in early ARDS than in intermediate or late ARDS. The
      surfactant pool increased in the early phase and decreased in the intermediate or
      late phase of the syndrome. The qualitative alterations of surfactant consist of
      reduced phospholipid content in the surfactant structures with good surface
      properties; moreover, there was a considerable decrease in the percentage of
      phosphatidylcholine and phosphatidylglycerol, followed by an increase in
      phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, and
      sphingomyelin in all three phases of ARDS compared to the control group.
      Lysophosphatidylcholine was detectable only in late ARDS. CONCLUSION: Total
      surfactant phospholipids, surfactant components, and inflammatory markers such as
      PAF, cells, and proteins were affected in patients with ARDS. These factors,
      undergoing quantitative alterations during the course of ARDS, could have a
      significant role in the pathogenesis and evolution of ARDS.

PMID- 9609407
TI  - Hyperlactatemia during acute severe asthma.
AB  - OBJECTIVE: To evaluate arterial lactate levels during treatment of acute severe
      asthma (ASA) and the prognostic value of arterial hyperlactatemia in ASA. DESIGN:
      Prospective study. SETTING: A respiratory intensive care unit (ICU) of a
      university hospital. PATIENTS: 29 consecutive patients admitted to the ICU for
      ASA not intubated on admission and with a peak expiratory flow (PEF) < 150 l/min
      or an arterial carbondioxide tension (PaCO2) > 40 mm Hg. All patients received
      standardized treatment during the first 24 h including i.v. and nebulized
      salbutamol, i.v. theophylline, and dexamethasone. MEASUREMENTS AND RESULTS:
      Arterial lactate levels were serially measured by an enzymatic method during the
      first 24 h following admission. On admission, the mean arterial lactate level was
      3.1 +/- 0.38 mmol/l (range 1.1-10.4); 17 patients (59%) had arterial
      hyperlactatemia with a lactate level > 2 mmol/l. No difference was found in
      lactate levels between patients with progressively worsening asthma and those
      with an acute onset of severe asthma. No correlation was found between arterial
      lactate levels on admission, on the one hand, and respiratory rate (RR), heart
      rate, PEF, pH, PaCO2, arterial oxygen tension, potassium, phosphorus, creatine
      kinase, or transaminase values on admission, on the other hand. All patients
      developed an important but transient increase in arterial lactate levels during
      treatment, with a peak at 7.72 +/- 0.46 mmol/l and a mean elevation of 4.62 +/-
      0.45 mmol/l (range 0.4-12.1), from the initial admission value contrasting with a
      significant clinical improvement assessed by RR, PEF, and arterial blood gas
      parameters. CONCLUSION: This study suggests that, in ASA, arterial
      hyperlactatemia is frequently present on admission to the ICU. Delayed
      hyperlactatemia is a constant finding during treatment of ASA. Initial or delayed
      hyperlactatemia seems of no prognostic value because none of the patients
      required mechanical ventilation. The effects of therapy for acute asthma on
      lactate metabolism still need to be studied.

PMID- 9609408
TI  - Acute normovolaemic haemodilution does not aggravate gastric mucosal acidosis
      during cardiac surgery.
AB  - OBJECTIVE: Acute normovolaemic haemodilution with subsequent autologous blood
      transfusion after surgery is widely used to reduce homologous blood requirements
      during cardiac surgery. The hypothesis tested was whether a low intraoperative
      haematocrit (Hct) resulting from haemodilution decreases gastric mucosal pH
      (pHi). DESIGN: Prospective clinical investigation. SETTING: University Hospital
      of Vienna, Austria. PATIENTS: 16 consecutive patients scheduled for elective
      cardiac surgery. INTERVENTIONS: The patients were randomly assigned to one of two
      groups: In 10 patients (group 1), 500 ml of blood was withdrawn and stored after
      anaesthesia induction. An equal amount of 6% hydroxyethyl starch was
      simultaneously infused. After discontinuation of cardiopulmonary bypass (CPB),
      the autologous blood unit was transfused. Six patients (group 2), who were not
      subjected to haemodilution and autologous blood transfusion served as controls.
      In all patients, a gastric tonometry probe was inserted. MEASUREMENTS AND
      RESULTS: Measurements of pHi and Hct were performed before and after acute
      normovolaemic haemodilution, during pulsatile hypothermic (30-32 degrees C) CPB,
      after rewarming, and 30 min after autologous blood transfusion in group 1, and at
      corresponding time intervals in group 2. Repeated measures analysis of variance
      and the Mann-Whitney U test were used for statistical analysis. Data are
      presented as means +/- standard error of the mean. Haemodilution in group 1
      caused a significant and persistent decrease in Hct (after haemodilution in group
      1 34 +/- 1 vs 40 +/- 1% in group 2). In both groups, pHi decreased during
      rewarming and after termination of CPB. However, in group 1, pHi was better
      preserved than in group 2 (rewarming: 7.44 +/- 0.02 vs 7.34 +/- 0.04; after CPB:
      7.38 +/- 0.03 vs 7.28 +/- 0.02; p < 0.05). CONCLUSIONS: Acute normovolaemic
      haemodilution does not aggravate gastric mucosal acidosis during cardiac surgery.

PMID- 9609405
TI  - Cardiac dysfunction in sepsis: new theories and clinical implications.

PMID- 9609409
TI  - Ibuprofen does not impair renal function in patients undergoing infrarenal aortic
      surgery with epidural anaesthesia.
AB  - OBJECTIVE: To investigate the effect of preoperative ibuprofen administration on
      renal function during and after infrarenal aortic surgery under thoracolumbar
      epidural anaesthesia (EPA). DESIGN: A prospective randomised, double-blinded
      clinical study. SETTING: Operation room and intensive care unit in a university
      hospital. PATIENTS: Twenty-six consecutive patients scheduled for elective
      infrarenal aortic surgery. INTERVENTIONS: The patients were prospectively
      randomised to receive 400 mg ibuprofen intravenously (i.v.) or a placebo aliquot
      before surgery. MEASUREMENTS AND RESULTS: We assessed renal function by
      calculating creatinine clearance, and fractional sodium excretion before surgery
      (baseline), 1 h after cross-clamping (intraoperative), 6 h after cross-clamping
      (postoperative) and 24 h after cross-clamping (on the 1 st postoperative day). At
      each point in time, we additionally registered haemodynamics and determined the
      plasma concentration of 6-keto-PGF1alpha (stable metabolite of prostacyclin,
      PGI2), bicyclic PGE2 (stable metabolite of PGE1 E2), active renin, aldosterone
      and vasopressin by radioimmunoassays. Throughout the observation period the renal
      function parameters mostly remained within the normal range without a significant
      difference between ibuprofen- and placebo-treated patients (creatinine clearance:
      baseline 41 +/- 3 vs 38 +/- 6, intraoperative 57 +/- 8 vs 64 +/- 11,
      postoperative 64 +/- 9 vs 56 +/- 9, first postoperative day 43 +/- 5 vs 47 +/- 6
      ml x min x m(-2), means +/- SEM). The plasma levels of 6-keto-PGF1alpha (68 +/- 8
      vs 380 +/- 71* ng x l(-1)), bicyclic PGE2 (57 +/- 5 vs 88 +/- 9* ng x l(-1)) and
      vasopressin (14 +/- 7 vs 45 +/- 10* ng x l(-1), p < 0.0125), however, were
      significantly higher during the intraoperative period in the placebo-treated
      patients. CONCLUSION: The inhibition of endogenous prostaglandin release by
      ibuprofen does not substantially impair renal function during infrarenal aortic
      surgery under EPA.

PMID- 9609410
TI  - Predictive value of interleukin 6 (IL-6), interleukin 8 (IL-8) and gastric
      intramucosal pH (pH-i) in major abdominal surgery.
AB  - OBJECTIVE: To study plasma concentrations of interleukin 6 (IL-6) and interleukin
      8 (IL-8) in patients with splanchnic hypoxia, as documented by gastric
      intramucosal measurements (pH-i), during major abdominal surgery and the
      relationship between IL-6 and IL-8 concentrations and postoperative complications
      as well as clinical outcome. DESIGN: A prospective study. PATIENTS: Twelve
      patients scheduled for major abdominal surgery with no evidence of coexisting
      infectious disease. RESULTS: Six out of seven samples from patients with
      postoperative complications showed intraoperative pH-i levels lower than 7.32 and
      IL-6 levels higher than 300 pg/ml. Seven out of nine samples from patients
      without complications showed pH-i levels higher than 7.32 and IL-6 levels lower
      than 300 pg/ml. The difference in the pattern of distribution was statistically
      significant (p < 0.01). Only two out of seven samples of patients with
      postoperative complications showed intraoperative pH-i levels lower than 7.32 and
      IL-8 levels higher than 60 pg/ml. It was not possible to identify a clear
      distribution pattern of data points for IL-6 and IL-8 during the postoperative
      period. CONCLUSIONS: Intraoperative splanchnic ischemia, as documented by gastric
      intramucosal pH-i, is directly correlated to the increase of IL-6 plasma levels
      and to the incidence of postoperative complications, while IL-8 levels showed no
      correlation with surgical complications.

PMID- 9609411
TI  - Antithrombin III (ATIII) replacement therapy in patients with sepsis and/or
      postsurgical complications: a controlled double-blind, randomized, multicenter
      study.
AB  - BACKGROUND: ATIII is decreased in sepsis and/or shock and its baseline value
      correlates with mortality. The efficacy of ATIII therapy on mortality was
      assessed in a selected group of patients admitted to the intensive care unit
      (ICU) in a double-blind, randomized, multicenter study. METHODS: 120 patients
      admitted to the ICU with an ATIII concentration < 70% were randomized to receive
      ATIII (total dose 24000 units) or placebo treatment for 5 days; 56 patients had
      septic shock. RESULTS: ATIII concentrations in the treated group remained
      constant throughout the treatment period (range 97-102%). The Kaplan-Meier
      analysis showed no difference in overall survival between the two groups: 50 and
      46% for ATIII and placebo, respectively. Septic shock and hemodynamic support
      were unbalanced in the two groups at admission. Therefore the Cox analysis was
      carried out after adjusting for these two variables. Treatment with ATIII
      decreases the risk of death with an odds ratio (OR) of 0.56. Of the covariates
      analyzed, septic shock and the baseline multiple organ failure score were
      negatively associated with survival and plasma activity level was positively
      associated with survival with an OR of 0.97 for each 1% increase in the ATIII
      plasma concentration at baseline. CONCLUSIONS: The results of ATIII treatment in
      this population of patients suggests that replacement therapy reduces mortality
      in the subgroup of septic shock patients only.

PMID- 9609412
TI  - Bioavailability of ciprofloxacin after multiple enteral and intravenous doses in
      ICU patients with severe gram-negative intra-abdominal infections.
AB  - BACKGROUND: Few data are available on the pharmacokinetics of multiple enteral
      dosing of ciprofloxacin in critically ill intensive care patients and none for
      those with severe gram-negative intra-abdominal infections (GNIAI). OBJECTIVE: To
      determine the bioavailability of enteral ciprofloxacin in tube-fed intensive care
      patients with severe GNIAI. DESIGN: A randomized crossover study. SETTING:
      University-based medical center. PATIENTS: 5 critically ill intensive care
      patients with GNIAI and an estimated creatinine clearance > 25 ml/ min who
      received continuous tube feeding. INTERVENTIONS: Multiple doses of enteral 750 mg
      b.i.d. versus 400 mg b.i.d.i.v. ciprofloxacin. MEASUREMENTS: The calculated 12-h
      area under the serum concentration versus time curve after 750 mg b.i.d. enteral
      dosing was equivalent to that after 400 mg b.i.d.i.v. The mean bioavailability of
      enteral dosing was 53.1% [95% confidence interval (CI) 43.5-62.8]. In seven
      additional patients, the mean serum steady-state concentration at 2 h after
      enteral administration was 3.9 microg/ml (95% CI 1.9-5.9), not significantly
      different from that found in the crossover study (p = 0.4). CONCLUSIONS: In tube
      fed intensive care patients with severe GNIAI, the bioavailability of enteral
      ciprofloxacin is adequate.

PMID- 9609413
TI  - Training is required to improve the reliability of esophageal Doppler to measure
      cardiac output in critically ill patients.
AB  - OBJECTIVES: Assessment of and effect of training on reliability of esophageal
      Doppler (ED) versus thermodilution (TD) for cardiac output (CO) measurement.
      DESIGN: Prospective study. SETTING: Intensive care unit of a university hospital.
      PATIENTS: 64 consecutive critically ill patients requiring a pulmonary artery
      catheter, sedation, and mechanical ventilation. INTERVENTIONS: Esophageal Doppler
      CO measurements were performed by the same operator, whereas TD CO measurements
      were carried out by other independent operators. A training period involving the
      first 12 patients made the operator self-confident. In the remaining patients,
      the reliability of ED was assessed (evaluation period), using correlation
      coefficients and the Bland and Altman diagram. Between training and evaluation
      periods, correlation coefficients, biases, and limits of agreement were compared.
      MEASUREMENTS AND RESULTS: During training and evaluation periods, 107 and 320 CO
      measurements were performed in 11 out of 12 patients and in 49 out of 52
      patients, respectively. Continuous CO monitoring was achieved in 6 out of 11
      patients and in 38 out of 49 patients during training and evaluation periods,
      respectively. Between the two periods, correlation coefficients increased from
      0.53 to 0.89 (p < 0.001), bias decreased from 1.2 to 0.1 l x min(-1) (p < 0.001),
      and limits of agreement decreased from 3.2 to 2.2 l x min(-1) (p < 0.001).
      CONCLUSION: A period of training involving no more than 12 patients is probably
      required to ensure reliability of CO measurement by ED.

PMID- 9609414
TI  - Critical care research and pre-emptive informed consent: a practical approach
      used in Chris Hani Baragwanath ICU.
AB  - OBJECTIVES: 1) To establish a protocol within international and local ethical
      guidelines to obtain informed consent for critical care research, overcoming
      constraints previously described and 2) To evaluate eventual recruitment using
      this protocol. DESIGN: Prospective descriptive study. SETTING: Multidisciplinary
      ICU in a community-based university teaching hospital. PATIENTS AND PARTICIPANTS:
      Following approval by the University Ethics Committee and Hospital Review Board,
      patients admitted between January and May 1996 were assessed on weekdays for
      potential enrollment into existing clinical trials. Discussion with potential
      candidates and/or next-of-kin occurred at the earliest opportunity and informed
      consent was obtained preemptively. Next-of-kin was notified if enrollment
      subsequently occurred. We evaluated the number of patients screened, the number
      of potential study candidates, the number for whom consent was obtained or
      refused and the number subsequently enrolled. INTERVENTIONS: None RESULTS: Of 249
      patients screened, 149 (60%) did not meet the inclusion criteria. Of 100
      potential study candidates (40% of all patients screened), we failed to make
      contact with the next-of-kin in 29 cases (12% of all patients screened). Thus 71
      patients or next-of-kin were counselled (28% of all patients screened). In all,
      30 patients (12% of all patients screened) were subsequently enrolled into a
      study. CONCLUSIONS: A policy of pre-emptive informed consent enabled us to
      overcome some of the problems previously experienced in our unit with regards to
      patient enrollment in critical care research. Although overall recruitment
      remained low, predictions for future enrollment can be made from this study.

PMID- 9609415
TI  - Oxygen delivery and consumption in surfactant-depleted newborn piglets.
AB  - OBJECTIVE: To study the relationship between oxygen (O2) delivery (DO2) and O2
      consumption (VO2) in surfactant-depleted newborn piglets. DESIGN: Prospective
      animal study. SETTING: Hospital surgical research laboratory. SUBJECTS: Twenty
      six anesthetized and ventilated newborn piglets. INTERVENTIONS: Twenty of the
      animals were subjected to repeated saline lung lavages, and then assigned to
      either the saline group or the L-NAME group. The other six animals without lavage
      were studied as the control group. Piglets in the L-NAME group and the control
      group received 3 mg/kg of N(omega)-nitro-L-arginine methyl ester (L-NAME, an
      inhibitor of NO synthase) i.v.; and those in the saline group received the same
      volume of saline i.v. MEASUREMENTS AND RESULTS: Cardiac output (CO) was measured
      and arterial and mixed venous blood gases were analyzed. DO2, O2 extraction ratio
      (O2ER) and VO2 were calculated. Plasma hypoxanthine was analyzed. In the lung
      lavaged groups, cardiac index, DO2 and VO2 decreased significantly after L-NAME
      i.v. but not after saline i.v. Further, the decrease in VO2 in the L-NAME group
      correlated with the decrease in DO2 (r = 0.83, p < 0.001). In the control group,
      cardiac index and DO2, but not VO2, decreased significantly after L-NAME i.v.
      Simultaneously, O2ER increased significantly. Plasma hypoxanthine was not
      modified by lung lavage but increased after L-NAME i.v. in both the L-NAME and
      control groups. CONCLUSION: These data suggest that O2 supply dependency is
      present in surfactant-depleted newborn piglets.

PMID- 9609416
TI  - Recurrent hydrochlorothiazide-induced pulmonary edema.
AB  - Hydrochlorothiazide-induced pulmonary edema is an unusual but life-threatening
      adverse reaction. It causes hypoxemia, hypotension, tachycardia, fever, and
      occasionally electrocardiographic and echocardiographic abnormalities. The
      mechanism of production is, probably, idiosyncratic.

PMID- 9609417
TI  - Sequential production of leukaemia inhibitory factor by blood cell culture in
      patients with ARDS.
AB  - OBJECTIVE: Leukaemia inhibitory factor (LIF) is a polyfunctional cytokine
      integrated in cytokine networks and its concentration has been shown to be
      elevated in bronchoalveolar lavage fluid of patients with the acute respiratory
      distress syndrome (ARDS). The aim of our study was to evaluate the production of
      LIF by culturing blood cells from patients with ARDS. PATIENTS: 8 patients with
      ARDS, 8 patients with pneumonia and 5 healthy subjects. MEASUREMENTS AND RESULTS:
      The blood samples were taken on day 1 after onset of ARDS. LIF was measured, in
      the cell-free supernatant, with an enzyme-linked immunosorbent assay after 24 h,
      48 h and 72 h of blood cell culture. LIF was detectable in some patients in the
      ARDS group: at i) at 24 h and 48 h: in 2 patients ii) at 72 h in 4/5 patients
      (140 +/- 231 pg/ml). Only in the 4 patients in whom LIF was measured at 72 h was
      ARDS associated with the multiple organ dysfunction syndrome. Furthermore, among
      the 5 patients with ARDS who subsequently died, 4 had a detectable LIF.
      CONCLUSIONS: We have observed that LIF was produced only in ARDS, but not in all
      patients. The production of LIF seems to be a good indicator of the severity of
      ARDS. These preliminary results must be confirmed by a larger study.

PMID- 9609418
TI  - Severe hyperthermia during tetrabenazine therapy for tardive dyskinesia.
AB  - We recently observed a 45-year-old patient with a history of psychiatric illness
      who presented with severe hyperthermia (rectal temperature above 41 degrees C)
      with intense rhabdomyolysis and liver cytolysis during tetrabenazine therapy for
      neuroleptic tardive dyskinesia. In addition to tetrabenazine, this patient took
      lorazepam and two antidepressant drugs: clomipramine, a potent serotonin-reuptake
      inhibitor, and mianserin. Hyperthermia responded to parenteral sodium dantrolene
      and oral bromocriptine administration. The significant role of tetrabenazine (a
      central nervous system dopamine-depleting drug) and the contribution of
      antidepressants to the mechanism of this neuroleptic malignant syndrome - like
      hyperthermia are discussed.

PMID- 9609419
TI  - Intensive care training and specialty status in Europe: international
      comparisons. Task Force on Educational issues of the European Society of
      Intensive Care Medicine.
AB  - OBJECTIVE: To describe current arrangements for postgraduate training and
      speciality status for intensive care medicine in Europe, and to compare these
      with three other geographical regions: the Middle East, North America, and
      Australia and New Zealand. METHODS: An iterative survey, by questionnaire and
      direct discussion, of council members of the European Society of Intensive Care
      Medicine, national specialist societies with involvement in intensive care, and
      national experts, representing four geographical regions and 47 countries.
      RESULTS: For the purposes of analysis, countries with common training structures
      have been grouped together; the denominator therefore includes both countries and
      regions. Formal training programmes in intensive care medicine (ICM) are
      available in 18 (85%) of the 21 countries or regions surveyed. Twelve (57%) offer
      multidisciplinary access to intensive care training with a common core
      curriculum. In six (28%) training in ICM is available solely through anaesthesia.
      The duration of intensive care training required for recognition as a specialist
      in the 18 countries or regions with a formal programme ranges from 18 to 30
      months, with a median of 24 months. All countries assess competence in intensive
      care, but methods for doing so vary widely. Eighteen countries or regions offer
      specialist registration (accreditation) in ICM; in 12 this is provided as dual
      accreditation in a base speciality and in ICM. CONCLUSIONS: There is substantial
      support for multidisciplinary training in ICM, as demonstrated by collaborative
      interspeciality developments in many countries. We propose that these national
      developments should be strengthened within Europe by the recognition of 'supra
      speciality' status for ICM by the European Commission, and by the establishment
      of a multidisciplinary Board for training in ICM, with international agreement on
      core competencies and duration of training programmes, and a common approach to
      the assessment of competence through formal examination.

PMID- 9609421
TI  - Inhaled nitric oxide in patients with pulmonary embolism.

PMID- 9609422
TI  - Randomized study of intracorporeal laser lithotripsy versus extracorporeal shock
      wave lithotripsy for difficult bile duct stones.
AB  - BACKGROUND: Endoscopic treatment modalities are well established for the removal
      of bile duct stones. For the small percentage of stones that are difficult or
      impossible to extract by conventional means, more sophisticated endoscopic
      techniques or associated modalities such as intracorporeal laser lithotripsy
      (ILL) and extracorporeal shock wave lithotripsy (ESWL) have to be applied. Little
      is known, however, about the relative value of these different techniques. We
      therefore compared endoscopic ILL with ESWL in patients with difficult bile duct
      stones in a prospective randomized study. METHODS: The study included 60 patients
      (35 women; mean age 70+/-15 years) with bile duct stones in whom standard
      extraction failed (n=33) or in whom the papilla was not accessible, thus
      requiring percutaneous access (n=27). They were randomized to receive ESWL under
      fluoroscopic targeting (maximum discharge number per session: 6000) or ILL using
      a pulsed dye laser with an automatic stone recognition system, which was mostly
      performed (28 of 30 cases) under cholangioscopic control. Endoscopic removal of
      fragments was attempted within the subsequent (ESWL) or the same (ILL) session.
      Failure was defined as failure to remove all ductal stones/fragments after a
      maximum of three lithotripsy sessions. RESULTS: There were no statistical
      differences in background variables between the two groups. Bile duct clearance
      was achieved in 22 of 30 patients (73%) in the ESWL group and in 29 of 30
      patients (97%) in the ILL group (p < 0.05). The number of treatment sessions
      (ESWL 3.0+/-1.3; ILL 1.2+/-0.4; p < 0.001) and the duration of treatment (ESWL
      3.9+/-3.5 days; ILL 0.9+/-2.3 days; p < 0.001) were also significantly different
      in favor of ILL. Two minor complications occurred in each group; there was no 30
      day mortality. Crossover therapy to ILL led to stone removal in seven of the
      eight cases in which ESWL failed, whereas ESWL fragmented the stone in the single
      patient in whom ILL failed. CONCLUSIONS: ILL is more effective in the treatment
      of difficult bile duct stones than ESWL in terms of stone clearance rate and
      treatment duration.

PMID- 9609423
TI  - EUS-guided, fine-needle aspiration biopsy using a new mechanical scanning
      puncture echoendoscope.
AB  - BACKGROUND: A new mechanical sector scanning echoendoscope designed for EUS
      guided, fine-needle aspiration biopsy (FNAB) was prospectively evaluated. The
      technical feasibility, safety, and histocytologic FNAB results are reported.
      METHODS: Eighty-six patients underwent 106 FNAB procedures. The new echoendoscope
      has a 2.8 mm accessory channel and an elevator. Target sites: pancreas 58, lymph
      nodes 43, and miscellaneous lesions 5. Lesions were punctured with a 0.7 mm
      needle and submitted for cytologic and histologic examination. Definitive
      diagnosis was by surgery or clinical follow-up. RESULTS: The wide scanning field
      (250 degrees) enabled easy sonographic orientation for FNAB. Longitudinal needle
      visibility was "good" in 93% and 71% of transesophageal and transgastric
      procedures, respectively, but were compromised during most transduodenal
      procedures. Needle penetration of indurated pancreatic lesions failed in two
      patients, and in four additional patients pancreatic sampling succeeded only
      after a second attempt using an automated spring-loaded device. The mean number
      of passes was three. Ten percent of FNAB specimens were "inadequate"; excluding
      these, the diagnostic accuracy rate was 97%; sensitivity for malignancy was 88.5%
      and specificity was 100%. CONCLUSION: EUS-guided FNAB is feasible, safe, and
      accurate using the new mechanical puncture echoendoscope. Needle visibility needs
      to be improved, particularly for transduodenal FNAB.

PMID- 9609420
TI  - The American-European Consensus Conference on ARDS, part 2. Ventilatory,
      pharmacologic, supportive therapy, study design strategies and issues related to
      recovery and remodeling.
AB  - The acute respiratory distress syndrome (ARDS) continues as a contributor to the
      morbidity and mortality of patients in intensive care units throughout the world,
      imparting tremendous human and financial costs. During the last ten years there
      has been a decline in ARDS mortality without a clear explanation. The American
      European Consensus Committee on ARDS was formed to re-evaluate the standards for
      the ICU care of patients with acute lung injury (ALI), with regard to ventilatory
      strategies, the more promising pharmacologic agents, and the definition and
      quantification of pathological features of ALI that require resolution. It was
      felt that the definition of strategies for the clinical design and coordination
      of studies between centers and continents was becoming increasingly important to
      facilitate the study of various new therapies for ARDS.

PMID- 9609424
TI  - Characterization of biliary strictures using intraductal ultrasonography:
      comparison with percutaneous cholangioscopic biopsy.
AB  - BACKGROUND: We determined the accuracy of intraductal ultrasonography (IDUS) in
      distinguishing between bile duct cancer and benign bile duct disease. METHODS:
      Patients (n=42) who required bile duct biopsy using percutaneous transhepatic
      cholangioscopy (PTCS) to evaluate bile duct strictures or filling defects were
      studied. A thin-caliber ultrasonic probe (2.0 mm diameter and 20 MHz frequency)
      was inserted into the bile duct, and its images were prospectively reviewed
      before PTCS. RESULTS: Disruption of the bile duct wall structure, seen on IDUS,
      was associated with malignancy in 25 of 26 patients. When IDUS demonstrated a
      lesion with normal bile duct structure, six of nine patients were found to have
      no malignancy. IDUS demonstrated no intraductal lesion in seven patients, and
      bile duct biopsy also did not indicate cancer in any of these patients. The
      accuracy, sensitivity, and specificity of IDUS for diagnosing bile duct cancer
      were 76%, 89%, and 50%, respectively. When used in tandem with IDUS, the
      sensitivity of bile cytology (64%) and PTCS (93%) improved to 96% and 100%,
      respectively. CONCLUSIONS: The accuracy of IDUS for diagnosing bile duct cancer
      was less than that of PTCS (95%). However, the sensitivity for bile cytology, or
      bile duct biopsy improved when performed in combination with IDUS.

PMID- 9609425
TI  - Utility of preoperative fiberoptic flexible sigmoidoscopy in the evaluation of
      patients with suspected gynecologic malignancy.
AB  - BACKGROUND: Fiberoptic flexible sigmoidoscopy (FFS) is routinely requested
      preoperatively as part of evaluation of pelvic masses to exclude colonic
      involvement by the tumor or concurrent colonic neoplasm. The aim of our study was
      to evaluate the utility of preoperative FFS in patients with suspected
      gynecologic malignancy. METHODS: FFS, performed using a 60 cm sigmoidoscope,
      evaluated (1) presence of bowel involvement by the tumor, (2) extrinsic
      compression by the tumor, and (3) presence of colonic neoplasms. FFS findings
      were correlated with surgical findings. RESULTS: A total of 107 women underwent
      preoperative FFS and subsequent surgery. Eleven patients (11%) had lower
      gastrointestinal symptoms. At surgery, 63% of pelvic tumors were malignant and
      37% were benign. The most common abnormality at FFS was colonic polyps in 23
      patients (21%). Colonic adenomas were found in 11 patients (10%). Extrinsic
      compression by the tumor without mucosal abnormalities was seen in 15 patients
      (14%). The most common intraoperative finding was tumor adhering to the bowel in
      18 patients requiring dissection, but only 1 patient required bowel resection.
      Eight of these 18 patients had preoperative lower gastrointestinal symptoms. All
      15 patients with extrinsic compression at FFS had tumor adhering to the bowel.
      CONCLUSIONS: Pelvic masses cause extrinsic compression at FFS in 14% of patients.
      This is suggestive of tumor adherent to the bowel at surgery. However, bowel
      resection is rarely required because of tumor involvement. Most patients with
      bowel adherence by tumor have lower gastrointestinal symptoms. Colonic adenomas
      are found in one tenth of patients, mostly in patients older than 50 years of
      age. Preoperative FFS does not change the surgical management of pelvic tumors.
      Screening FFS is indicated in all patients with pelvic tumors over age 50, as in
      persons with average risk, but is otherwise unnecessary in evaluation of pelvic
      masses.

PMID- 9609427
TI  - Endoscopic retrograde cholangiopancreatography under general anesthesia:
      indications and results.
AB  - BACKGROUND: Conscious sedation is usually used during endoscopic retrograde
      cholangiopancreatography (ERCP). Little is known about the indications and
      outcomes for ERCP in patients who cannot undergo conscious sedation and therefore
      require general anesthesia. We retrospectively evaluated the indications and
      outcome for patients undergoing ERCP who required general anesthesia at four
      teaching hospitals over a 2-year period. METHODS: Of 1200 ERCPs performed over a
      2-year period, 65 patients required general anesthesia. Retrospective chart
      analysis was undertaken to determine indications and outcomes of ERCP performed
      under general anesthesia. Eleven patients underwent sphincter of Oddi manometry.
      RESULTS: The major indication for general anesthesia was substance abuse.
      Therapeutic intervention was successful in 45 of 48 patients; 6 of the 63
      patients had complications, all mild and not related to the anesthesia. Sphincter
      of Oddi manometry was normal in 7 patients; 4 patients had elevated basal
      pressures. CONCLUSIONS: ERCP under general anesthesia may be considered when
      conscious sedation fails to achieve a satisfactory level of sedation for a
      successful and safe ERCP. Procedure-related complication rates appear to be
      comparable if not lower with general anesthesia.

PMID- 9609426
TI  - Outcome in patients with bifurcation tumors who undergo unilateral versus
      bilateral hepatic duct drainage.
AB  - BACKGROUND: There is much controversy as to the importance of establishing
      drainage of both liver lobes in malignant hilar obstruction. The purpose of the
      present study was to compare survival data in patients with malignant hilar
      obstruction, stratified according to the Bismuth classification, who had
      cholangiography with filling of one or both hepatic ducts and subsequently
      endoscopic or percutaneous drainage of one or both ducts. METHODS: A
      retrospective review was performed for the time period from July 1990 to July
      1995, and 224 patients were identified with a presumed diagnosis of a bifurcation
      tumor. All x-ray films were reviewed and 150 patients finally diagnosed as hilar
      tumor were classified according to Bismuth type I, II, or III. Type II and III
      patients were further subclassified with respect to contrast injection into a
      single or both hepatic duct systems and whether one or both sides were eventually
      drained. RESULTS: Data were obtained in 141 patients (4 patients still alive);
      there were 43 type I, 58 type II, and 40 type III. Type II and III patients were
      divided into three groups: group A, one lobe opacified with same lobe drained;
      group B, both lobes opacified with both lobes drained; and group C, both lobes
      opacified with one lobe drained. Overall median survival for type I, II, and III
      patients was 160, 131, and 62 days, respectively. Among type II and III patients
      the median survivals of groups A, B, and C were 145, 225, and 46 days,
      respectively. Survival was significantly longer in group A vs. group C (p <
      0.001), group B vs. group C (p < 0.001, and group A + B (165 days) vs. group C p
      < 0.001). There was no difference in group A + B versus type I (p=0.90). In
      addition, when comparing single drain only (group A + C, 80 days) versus double
      drains (group B, 225 days), there was a significant survival advantage (p <
      0.0001). CONCLUSION: In bifurcation tumors the best survival was noted in those
      with bilateral drainage, and the worst survival in those with cholangiographic
      opacification of both lobes but drainage of only one.

PMID- 9609428
TI  - Emergency endoscopic retrograde cholangiopancreatography in critically ill
      patients.
AB  - BACKGROUND: The aim of this study was to assess the frequency, indications,
      yield, and outcome of emergency endoscopic retrograde cholangiopancreatography
      (ERCP) in critically ill patients. METHODS: Records of all intensive care unit
      patients undergoing emergency ERCP were reviewed over a 40-month period.
      Indications, findings, therapeutic interventions, and survival were analyzed.
      Those requiring mechanical ventilation at the time of ERCP were in group A and
      those who did not were in group B. RESULTS: Of 1781 ERCPs, 32 (1.80%) were
      performed on intensive care unit patients. Fifteen patients belonged to group A
      (46.87%) and 17 (53.13%) to group B. The common bile duct was the duct of
      interest in 30 patients (94%) and was cannulated in 97%. Indications included
      possible biliary sepsis (68.75%), gallstone pancreatitis, and jaundice (12.5%
      each). The most common finding was choledocholithiasis (34%), followed by failure
      to fill the cystic duct (16%) and common bile duct stricture (9%). A normal
      examination was present in 18.75% of cases. Endoscopic therapy was required in
      66.6% of patients in group A and 70.5% of group B. The overall 30-day mortality
      was 25% (33% for group A and 17.6% for group B) and not related to the ERCP.
      CONCLUSIONS: Two percent of all ERCPs performed were on intensive care unit
      patients (47% requiring mechanical ventilation) primarily to evaluate for
      possible biliary sepsis. Technical success was not compromised by mechanical
      ventilation. Therapeutic intervention was required in more than two thirds of
      patients and the overall 30-day mortality was 25%.

PMID- 9609429
TI  - Push enteroscopy for obscure gastrointestinal bleeding yields a high incidence of
      proximal lesions within reach of a standard endoscope.
AB  - BACKGROUND: The use of push enteroscopy to evaluate patients with obscure
      gastrointestinal bleeding has increased in recent years, and diagnostic yield has
      been reported to be 50% to 65%. This yield may be an overestimate of accuracy, as
      some lesions found during enteroscopy are within reach of a standard endoscope.
      METHODS: Ninety-five patients underwent push enteroscopy for obscure
      gastrointestinal bleeding. There were 58 men and 37 women with a mean age of 67
      years (range 32 to 93 years). Diagnostic yield and patient outcome were assessed.
      RESULTS: A suspected source of bleeding was found in 39 of 95 patients (16 of
      these patients had endoscopic treatment of their lesions). Proximal lesions (at
      or above the main duodenal papilla) accounted for 25 of 39 sources (64%),
      including Cameron ulcers and arteriovenous malformations of the stomach/proximal
      duodenum. Distal lesions accounted for 14 of 39 sources (36%) with arteriovenous
      malformations (n=0) being most common. Patients who underwent some form of
      treatment (medical, surgical, or endoscopic) because of an enteroscopic finding
      had a statistically better outcome than patients without a lesion (73% vs. 47%, p
      < 0.05). CONCLUSIONS: Push enteroscopy identified a presumed bleeding source in
      41 % of patients with obscure gastrointestinal bleeding. However, 64% were within
      reach of a standard endoscope. Repeat standard endoscopy should be considered
      before push enteroscopy for obscure gastrointestinal bleeding, and during
      enteroscopy meticulous attention should be given to the proximal gastrointestinal
      tract in addition to the distal duodenum and jejunum.

PMID- 9609430
TI  - Risk of contamination of sterile biopsy forceps in disinfected endoscopes.
AB  - BACKGROUND: Previous studies have shown that pathogens may persist within
      bacterial biofilms in endoscope accessory channels despite high-level
      disinfection. Breaching the gastrointestinal mucosa with biopsy forceps
      contaminated at time of passage has the potential to cause cross-infection
      between patients. METHODS: We studied contamination risk of sterilized biopsy
      forceps passed through endoscopes after high-level disinfection. For each trial,
      five video colonoscopes, duodenoscopes, and gastroscopes were used. All
      endoscopes had been previously processed and stored for 10 or more hours. Sterile
      biopsy forceps were inserted and retrieved followed by vortexing the tips in 15
      mL of soy broth. Under a laminar flow hood, the broth was filtered through a 0.2
      microm millipore membrane and plated. Because of minimal bacterial growth
      resulting from the above, soy broth (> 20 mL) was flushed through two video
      colonoscopes, duodenoscopes, and gastroscopes on two occasions and collected. The
      effluent was plated using a sample of 0.1 mL dilution. The remaining suspension
      was passed through a millipore filter, and the filter was cultured. All cultures
      were incubated more than 48 hours. RESULTS: Biopsy forceps underwent a total of
      24 anaerobic and 75 aerobic cultures. Microbacterial growth occurred on 17
      plates: 7 from gastroscopes, 5 from colonoscopes, and 5 from duodenoscopes.
      Fifteen plates grew staphylococcus for a total of 21 colonies, 1 plate grew 1
      colony of propionibacter, 2 plates grew diphtheroids for a total of 4 colonies,
      and 1 plate grew a single colony of lactobacillus. Cultures from soy broth
      flushed through the various endoscopes grew on 5 plates: 3 from gastroscopes and
      2 from duodenoscopes grew a total of 8 colonies of staphylococcus. CONCLUSIONS:
      With proper cleaning technique, a 20-minute soak in 2% glutaraldehyde is
      effective in disinfecting endoscopes. Although current procedures for endoscope
      disinfection remain imperfect, we found that in this clinical setting, infection
      of pathogenic gastrointestinal flora is unlikely when using sterile biopsy
      forceps.

PMID- 9609432
TI  - Subumbilical midline vascularity of the abdominal wall in portal hypertension
      observed at laparoscopy.
AB  - BACKGROUND: Large volume paracentesis is a common treatment of ascites. Injury to
      abdominal wall collateral veins during this procedure can lead to hemoperitoneum.
      Because of this concern, the midline below the umbilicus is often recommended as
      a site for paracentesis because of its presumed avascularity. METHODS: We
      examined the subumbilical peritoneal surface in 20 consecutive patients with
      liver disease undergoing diagnostic laparoscopy. This area was visualized by
      table tilting and confirmed by external finger compression. Nineteen patients had
      cirrhosis of various etiologies, and one had advanced fibrosis with evidence of
      portal hypertension. RESULTS: In these 20 patients, only 7 had avascular midlines
      below the umbilicus. Seven had small but definite veins running along the path of
      the urachus (median umbilical fold), and 6 had more prominent veins in this
      region. The internal landmarks in this region (median and medial folds) were
      frequently asymmetric with regard to the external appearance of the midline.
      CONCLUSION: The subumbilical midline in patients with portal hypertension is
      commonly vascular. When using this site for paracentesis, care should be
      exercised to identify venous structures with the narrow-gauge needle used to
      inject local anesthetic agent before placement of larger paracentesis needles.

PMID- 9609431
TI  - Effectiveness of premedication with pronase for improving visibility during
      gastroendoscopy: a randomized controlled trial.
AB  - BACKGROUND: Minute early gastric cancers can be removed with endoscopic mucosal
      resection techniques. However, early detection of these minute cancers with
      endoscopy is still difficult. For this purpose, use of a dye is helpful. To
      increase visibility further, gastric mucus should be removed before endoscopic
      examination. In this study, the effectiveness of premedication with pronase for
      improving visibility during gastroendoscopy was investigated. METHODS: From
      January through July 1996, outpatients scheduled for gastroendoscopy were
      randomly assigned to oral premedication with the antifoam agent
      dimethylpolysiloxane alone (n=34), with dimethylpolysiloxane plus sodium
      bicarbonate (n=32), or with dimethylpolysiloxane, sodium bicarbonate, and pronase
      (n=34). All were given about 10 minutes before the start of endoscopy. After
      inserting the endoscope, the endoscopist gave visibility scores at conventional
      endoscopy and after methylene blue spraying. RESULTS: Premedication with pronase
      significantly improved visibility before and after methylene blue spraying as
      compared with the two other groups pretreated without pronase. Pronase also
      significantly shortened the times for chromoendoscopic examination. Pronase had
      no significant effect on the culture of Helicobacter pylori. CONCLUSION:
      Premedication with pronase improved endoscopic visualization during conventional
      endoscopy and chromoendoscopy. Its routine use at gastroendoscopy is therefore
      recommended.

PMID- 9609433
TI  - Usefulness of laparoscopy with liver biopsy in the assessment of liver
      involvement at diagnosis of Hodgkin's and non-Hodgkin's lymphomas.
AB  - BACKGROUND: Staging of lymphoma at diagnosis determines therapeutic strategy and
      disease prognosis. Hepatic involvement, demonstrated by laparotomy or
      laparoscopy, is frequent in Hodgkin's and non-Hodgkin's lymphoma. However, it is
      unclear whether these procedures are still necessary or whether they should be
      replaced by less invasive techniques. METHODS: Laparoscopy-assisted liver
      biopsies, as well as laboratory studies, bone marrow biopsy, and thoracic and
      abdominal computed tomography, were performed as an initial staging evaluation in
      112 consecutive patients who were diagnosed with Hodgkin's or non-Hodgkin's
      lymphoma. RESULTS: Hepatic lymphomatous involvement was demonstrated in 18
      patients (16%). It was more frequent in non-Hodgkin's (24%) than in Hodgkin's
      (8%) lymphomas (p < 0.04) and among stage III and IV (24%) than stage I and 11
      (10%) patients (p < 0.05). The laparoscopic finding of white spots or nodules on
      the liver surface had a 100% specificity in the diagnosis of lymphomatous liver
      involvement. Conversely, hepatomegaly on both laparoscopy and computed
      tomography, as well as laboratory studies, had a low sensitivity and specificity.
      CONCLUSIONS: Laparoscopy-assisted liver biopsy was a useful technique to
      establish hepatic lymphomatous involvement, which was not identified by either
      computed tomography or laboratory studies.

PMID- 9609434
TI  - Increased selective biliary cannulation rates in the setting of periampullary
      diverticula: main pancreatic duct stent placement followed by pre-cut biliary
      sphincterotomy.
AB  - BACKGROUND: Selective biliary cannulation is often difficult when there is a
      periampullary diverticulum, especially when the papilla is within the
      diverticulum. We report eight such cases in which a new technique was used to
      achieve biliary access. METHODS: Among 4138 ERCPs, there were 246 cases (5.9%)
      with periampullary diverticula. Biliary cannulation initially failed in eight
      patients (3.3%), five of whom had previously undergone six failed attempts at
      other institutions. A technique was used whereby the papilla was kept out of the
      diverticulum by placement of a pancreatic duct stent. Needle-knife sphincterotomy
      was then performed followed by attempts to achieve biliary access. RESULTS:
      Biliary entry was immediately successful in five patients and successful at a
      second ERCP in two (overall success 87.5%). Two patients developed post-ERCP
      pancreatitis. CONCLUSIONS: When the papilla is within the periampullary
      diverticulum, placement of a main pancreatic duct stent keeps the papilla out of
      the diverticulum, thereby facilitating pre-cut needle-knife sphincterotomy and
      selective biliary cannulation.

PMID- 9609435
TI  - Emergency endoscopic ligation of actively bleeding gastric varices with a
      detachable snare.
AB  - BACKGROUND: Bleeding gastric varices (BGV) is a challenging condition whose
      management remains controversial and often empirical. METHODS: Over the past 6
      months, emergency ligation of BGV was performed in seven cirrhotic patients (five
      men, two women; age range 47 to 70 years) using a detachable snare. Child's grade
      was B in two and C in five patients. Two patients had a concurrent hepatocellular
      carcinoma. Three patients had been previously treated with either balloon
      tamponade or injection sclerotherapy for bleeding esophageal varices. RESULTS:
      Hemostasis was achieved in all patients. Morbidity consisted of fever in one
      case. Six snares passed spontaneously, one was removed from the stomach on follow
      up examination. Post-ligation ulcers were detected in all patients after
      treatment (mean diameter 7.4+/-2.1 mm) with no stigmata of recurrent hemorrhage.
      No early rebleeding was observed during hospital stay. On a mean follow-up of 3.8
      months (range 2 to 6 months), no digestive hemorrhage was recorded. Ligated
      gastric varices were significantly 'reduced in size in four patients.
      CONCLUSIONS: Emergency ligation with detachable snare is feasible and may be an
      alternative life-saving method of endoscopic hemostasis in BGV.

PMID- 9609436
TI  - Endoscopic injection and polypectomy for bleeding Brunner's gland hamartoma: case
      report and expanded literature review.

PMID- 9609438
TI  - Adenosquamous carcinoma of the pancreas: differentiation from pancreatic
      pseudocyst.

PMID- 9609437
TI  - Life-threatening complications of nasogastric administration of polyethylene
      glycol-electrolyte solutions (Golytely) for bowel cleansing.

PMID- 9609439
TI  - Elongated non-neoplastic colonic polyp: endoscopic features.

PMID- 9609440
TI  - Acute airway obstruction from insertion of a cuffed esophageal stent for
      malignant tracheoesophageal fistula.

PMID- 9609441
TI  - ERCP complicated by a retroperitoneal abscess caused by Haemophilus influenzae
      and Haemophilus parainfluenzae.

PMID- 9609442
TI  - Abdominal pain and rectal bleeding as a complication of biliary stent migration
      in a liver transplant recipient.

PMID- 9609443
TI  - EUS-guided FNA: a few caveats.

PMID- 9609444
TI  - Internet for endoscopists: surf or drown?

PMID- 9609445
TI  - Acute ulcer bleeding: a prospective randomized trial to compare Doppler and
      Forrest classifications in endoscopic diagnosis and therapy.

PMID- 9609446
TI  - Gallstone size and risk of pancreatitis.

PMID- 9609447
TI  - A comparison of omeprazole and placebo for bleeding peptic ulcer.

PMID- 9609448
TI  - Endoscopy teaching: time to get serious.

PMID- 9609449
TI  - Endoscopy in Australia.

PMID- 9609450
TI  - PanAmerican Congress of Gastroenterology.

PMID- 9609451
TI  - Percutaneous endoscopic gastrojejunostomy tube placement.

PMID- 9609453
TI  - "Novel technique" revisited.

PMID- 9609452
TI  - Modified push-PEG technique to facilitate reinsertion of the gastroscope.

PMID- 9609454
TI  - Overtube separation.

PMID- 9609455
TI  - Thin glomerular basement membrane nephropathy in adults.

PMID- 9609456
TI  - Tacrolimus in kidney transplantation. A clinical review.

PMID- 9609457
TI  - Detection of apoptotic cells in glomeruli of patients with IgA nephropathy.
AB  - The purpose of the present study was to determine the relationship between the
      existence of apoptotic cells in glomeruli, clinical or histopathological findings
      and response to treatment in patients with IgA nephropathy. Renal biopsy
      specimens were obtained from 23 patients with IgA nephropathy. These patients
      were divided into two groups: mild glomerular damage (12 patients), and severe
      glomerular damage (11 patients). The nick end-labelling method (TUNEL) and
      fluorescent staining (Hoechst 33258) were used for the detection of apoptotic
      cells. Five of 6 patients with apoptotic cells in the glomeruli detected by TUNEL
      were in the severe glomerular damage group, and only 1 patient was in the mild
      glomerular damage group. Apoptotic cells in glomeruli were also detected by
      fluorescent staining in 3 of 5 patients in the severe glomerular damage group who
      showed apoptotic cells in TUNEL. However, no apoptotic cells were detected in
      patients in the mild glomerular damage group in fluorescent staining. Mean levels
      of urinary protein excretion at the time of renal biopsy in the patients with
      apoptotic cells were significantly higher than those in patients without
      apoptotic cells (p < 0.01). The mean levels of creatinine clearance (Ccr) in the
      patients with apoptotic cells were slightly lower than those in patients without
      such cells. There were no significant differences in the levels of serum
      creatinine (s-Cr) and BUN in patients with or without apoptotic cells. In the
      severe glomerular damage group, urinary protein excretion after treatment in the
      patients with apoptotic cells was significantly improved compared with that in
      the patients without such cells (p < 0.01). It appears that the levels of
      proteinuria and renal function tests might be influenced by apoptosis in patients
      with IgA nephropathy. It is postulated that apoptosis may induce reduction of
      excess proliferative mesangial cells and/or infiltrated cells, and tissue repair.
      Thereafter, these histological alterations may improve proteinuria and renal
      function.

PMID- 9609458
TI  - Effect of intrauterine growth retardation on the clinical course and prognosis of
      IgA glomerulonephritis in children.
AB  - Intrauterine growth retardation (IUGR) resulting in a reduced number of nephrons
      is one of the nonimmune mechanisms that have been recently proposed as
      contributing to the progression of renal diseases. The purpose of our study was
      to determine whether IUGR has any effect on the clinical course and prognosis of
      IgA glomerulonephritis (IgA GN) in children. Fifty children with biopsy-proven
      IgA GN, who were followed for at least 3 years, were included. Six of the 50
      children (12%) had signs of IUGR at birth, defined as birth weight below the 10th
      percentile for gestational age. There were no significant differences in initial
      clinical presentation between children with IUGR and those without IUGR. However,
      in kidney biopsy specimens, we found a significantly higher mean percentage of
      sclerotic glomeruli in children with IUGR than in those without IUGR (33 vs. 13%,
      p < 0.015). At the end of the follow-up period, we observed a significantly
      higher incidence of arterial hypertension in children with IUGR than in those
      without IUGR (50 vs. 11 %, p < 0.05). Other differences between the two groups of
      children were not statistically significant. In conclusion, our study
      demonstrated an increased risk of the development of arterial hypertension and
      glomerulosclerosis in children with IgA GN who had suffered from IUGR with a
      birth weight below the 10th percentile for gestational age. IUGR may therefore
      help to identify early in the course of IgA GN those children who are at higher
      risk of an unfavorable course.

PMID- 9609459
TI  - A high glucose concentration stimulates the expression of monocyte chemotactic
      peptide 1 in human mesangial cells.
AB  - The mechanism of glomerular infiltration of monocytes remains unknown in diabetic
      nephropathy. We examined the effect of a high glucose concentration on monocyte
      chemotactic peptide 1 (MCP-1) expression in human mesangial cells (MCs) by using
      enzyme-linked immunosorbent assay and reverse transcription coupled with
      polymerase chain reaction (PCR). More than a 50% increase in the MCP-1 protein
      production was observed in MCs cultured in high-glucose medium (450 mg/dl) as
      compared to normal glucose (100 mg/dl; 1,496 +/- 75 vs. 966 +/- 15 pg/ml after 24
      h, 1,910 +/- 93 vs. 1,250 +/- 55 pg/ml after 48 h). Semiquantitative PCR showed
      that phorbol myristate acetate (100 nM) increased the ratio of PCR products for
      MCP-1 to housekeeping gene glyceraldehyde-3-phosphate dehydrogenase on
      densitometric results at 24 h by 2.7-fold, which was prevented by calphostin C
      (200 nM) pretreatment. High glucose increased the ratio by 3-fold as compared to
      normal glucose at 24 h (0.72 +/- 0.11 vs. 0.24 +/- 0.01). This was also
      suppressed by calphostin C pretreatment. These findings demonstrate that high
      glucose can directly increase MCP-1 expression in MCs, which may contribute to
      monocyte infiltration in diabetic nephropathy, and this is regulated by protein
      kinase C.

PMID- 9609460
TI  - The fibronectin production is increased by thrombospondin via activation of TGF
      beta in cultured human mesangial cells.
AB  - Thrombospondin (TSP) is a multifunctional glycoprotein that is synthesized by a
      variety of cells including mesangial cells (MCs). To clarify the effect of TSP on
      the pathogenesis of diabetic nephropathy, we studied the effect of glucose
      concentrations on TSP synthesis in cultured human MCs. Thereafter, the effects of
      TSP on the activation of transforming growth factor beta (TGF-beta) and
      fibronectin production were investigated in MCs. Incubating MCs with elevated
      glucose levels for 6 days resulted in an increase in TSP synthesis, measured by
      an enzyme-linked immunosorbent assay, both in culture media and cell layers.
      Treatment of MCs with TSP (final concentrations 1 and 5 microg/ml) for 24 h
      resulted in an increase (1.3- and 2.1-fold, respectively) in active TGF-beta,
      which was determined with an enzyme-linked immunosorbent assay using TGF-beta
      soluble receptor type II, in the culture media without having any effect on the
      production of total TGF-beta. Exposure of MCs to TSP caused enhancement of
      fibronectin production in both media and cell layers in a TSP dose-dependent
      manner with the maximum at a TSP concentration of 1 microg/ml. The TSP-induced
      increase in fibronectin production from MCs was completely prevented by
      concomitant treatment with 10 microg/ml anti-TGF-beta neutralizing antibody.
      These results indicate that the TSP production is promoted by a high ambient
      glucose concentration in human MCs and that TSP, in turn, causes an increase in
      fibronectin production via activation of TGF-beta.

PMID- 9609461
TI  - Urinary soluble HLA class I antigen in patients with minimal change disease: a
      predictor of steroid response.
AB  - In primary minimal change disease (MCD) and focal segmental glomerulosclerosis
      (FSGS), increased lymphocyte reactivity to renal antigens has been defined.
      Soluble HLA class I antigen (sHLA-I) is actively secreted by T and B lymphocytes
      when they are stimulated by mitogens, antigens and lymphokines. To determine if
      serum and urine sHLA-I levels could predict steroid response in patients with MCD
      and differentiate those from FSGS, we have investigated 45 healthy controls,
      biopsy-proven 17 patients with MCD (edema and 24-hour urine protein > 3.5 g/day),
      8 patients with FSGS (24-hour urine protein > 1 g/day) and 10 patients with
      membranous nephropathy (MGN) (24-hour urine protein > 1 g/day). Before and after
      prednisone therapy (1 mg/kg/day or 2 mg/kg/EOD for 8 weeks), the levels of serum
      and urinary sHLA-I were measured by ELISA (sHLA-STAT; Sangstat Co., Calif., USA).
      After 8 weeks of treatment, 10 patients with MCD were responders (MCD-CR) while
      the other 7 patients with MCD were nonresponders (MCD-NR). Three of 7 patients
      with MCD-NR were re-biopsied and finally diagnosed as FSGS. They were included in
      the data of patients with FSGS. In healthy controls, serum sHLA-I was detected
      (415 +/- 256 ng/ml), but urinary sHLA-I was not. At entry, there were no
      differences in age, sex, serum Cr and 24-hour urine protein among the patients
      with MCD-CR, MCD-NR and FSGS, but serum albumin was significantly elevated in
      patients with FSGS and MGN (p < 0.05). Serum sHLA-I levels were notably elevated
      in MCD-CR (1,040 +/- 1,066 ng/ ml), in MCD-NR (668 +/- 315 ng/ml) and in FSGS
      (713 +/- 790 ng/ml), but not in patients with MGN (444 +/- 86 ng/ml) when
      compared with controls (p < 0.05). On the other hand, urinary sHLA-I levels in
      MCD-NR (541 +/- 239 ng/mg Cr) and in FSGS (457 +/- 239 ng/mg Cr) were
      significantly higher than those in MGN (125 +/- 28 ng/mg Cr) and in MCD-CR(100 +/
      42 ng/mg Cr, p < 0.05) and these substantial differences were maintained for 8
      weeks. In all patients, serum and urinary sHLA-I levels were not reduced during 8
      weeks of steroid therapy. We conclude that elevated serum and urinary sHLA-I
      levels reflect increased cellular immune response and disease activity in
      patients with MCD and FSGS. In patients with MCD, urinary sHLA-I may be an easily
      measurable indicator of predicting steroid response, while MCD-NR with high
      urinary sHLA-I levels might be re-evaluated for the possibility of FSGS.

PMID- 9609462
TI  - Effect of increased hemodialysis dose on endogenous erythropoietin production in
      end-stage renal disease.
AB  - We investigated 20 patients (12 men and 8 women) with end-stage renal disease
      sustained on hemodialysis to determine the effect of 6 weeks of increased
      dialysis dose on endogenous erythropoietin production. Increased dialysis dose
      was achieved by increasing thrice-weekly dialysis treatment time from 4 to 4.5 h
      and switching from an MCA 160 dialyzer to an F80 dialyzer. The mean age of the
      study subjects was 51 +/- 13.8 years, and the mean duration of end-stage renal
      disease prior to the study was 31.4 +/- 55.5 months. All subjects were receiving
      recombinant erythropoietin for at least 4 months prior to the study. The dialysis
      dose was increased from a mean reduction of urea of 60.7 to 72%. At baseline, the
      group's mean hematocrit was 28.4 +/- 3.4%, the mean predialysis endogenous
      erythropoietin level was 9.1 +/- 4.5 (range 2.5-18.4) mU/ml, the mean reduction
      of urea was 60.7 +/- 4%, and the mean transferrin saturation was 22.6 +/- 15.5%.
      Mean thrice-weekly recombinant erythropoietin injections were administered
      intravenously after dialysis to each patient at a dose of 51 +/- 19 U/kg body
      weight. After 6 weeks of an increased dialysis dose, the mean hematocrit
      increased from 28.4 +/- 3.4 to 32.3 +/- 3.3% (p = 0.0001), while the mean serum
      endogenous erythropoietin level decreased from 9.1 +/- 4.5 (range 2.5-18.4) mU/ml
      to 6.1 +/- 3.2 (range 2.5-13.4) mU/ml (p = 0.0001). We conclude that the serum
      endogenous erythropoietin levels decrease with increased dialysis dose and that
      the increase in hematocrit following increased dialysis dose is probably not
      mediated by changes in endogenous erythropoietin.

PMID- 9609463
TI  - Eradication and follow-up of Helicobacter pylori infection in hemodialysis
      patients.
AB  - It is currently accepted that Helicobacter pylori (Hp) infection is crucial in
      the pathogenesis of peptic ulcer. Therefore, we developed a prospective study to
      assess the prevalence of Hp infection by the 13C Urea Breath Test (13C UBT) in 52
      hemodialysis patients, and we evaluated the efficacy of two consecutive
      eradication regimens in 23 positive patients with dyspepsia and/or on a
      transplantation list. The correlation between anti-Hp serology and 13C UBT
      results was also analyzed in 34 patients who were followed up during 18 months.
      The Hp prevalence by 13C UBT was 63.5% (33/52). The eradication rate after the
      first cycle of therapy (amoxicillin 500 mg/8 h and omeprazole 20 mg/12 h, 14
      days) was 60.8% (14/23). After the second cycle (clarithromycin 500 mg/12 h plus
      omeprazole 20 mg/12 h, 14 days), the eradication rate reached 82.6% (19/23). The
      serological procedure showed a good correlation with 13C UBT (about 80% sensitive
      and specific) when very restrictive diagnostic and eradication criteria were
      adopted. We conclude that an eradication rate higher than 80% can be reached
      after two consecutive cycles of dual therapy in hemodialysis patients. Anti-Hp
      serological tests must be cautiously interpreted in these patients.

PMID- 9609464
TI  - Transcription of the XRCC1 gene in kidneys of radiosensitive and radioresistant
      mice following whole-body irradiation.
AB  - The XRCC1 gene was described to play a role in the sensitivity of mammalian cell
      lines towards ionizing irradiation. Cells with a mutation of this gene present
      with decreased single-strand break repair and reduced recombination repair, show
      increased double-strand breaks, and the sister chromatid exchange is increased up
      to tenfold. The goal of our study was to investigate the transcription of this
      gene in the kidney following ionizing irradiation in the mouse, as this could be
      relevant to the pathogenetic mechanisms found in radiation nephropathy.
      Furthermore, we intended to examine whether radiation-sensitive mice would show a
      transcriptional pattern different from radiation-resistant mice. Radiation
      sensitive BALB/c/J/Him mice and radiation-resistant C3H/He/Him mice were whole
      body irradiated with X-ray at 2, 4, and 6 Gy and sacrificed 5, 15, and 30 min
      after irradiation. mRNA was isolated from kidney cortex and hybridized with
      probes for XRCC1 and beta-actin as a housekeeping gene control. Following
      irradiation at 2 Gy, radiation-resistant mice increased transcriptional levels of
      mRNA-XRCC1/mRNA-beta-actin as early as after 5 min, and 15 and 30 min after
      irradiation, XRCC1 transcription was still higher than in radiation-sensitive
      mice. At higher radiation doses, no differences were found. This finding is the
      first in vivo study on XRCC1 of this kind and may in part explain the differences
      in the radiation sensitivity between the two strains studied.

PMID- 9609465
TI  - Effect of mizoribine on glomerulonephritis of early-stage IgA nephropathy in ddY
      mice.
AB  - Immunopathological studies were performed to determine whether the glomerular
      injuries in ddY mice, a model for IgA nephropathy (Berger's disease), are
      influenced by treatment with mizoribine, a new immunosuppressive agent. The ddY
      mice were treated with a low (0.05 mg/ml) or a high (0.1 mg/ml) dose of
      mizoribine for 35 weeks. Flow cytometry analysis showed that there was a marked
      decrease in the number of B cells and IgA-bearing B cells. In immunofluorescence,
      the deposition of IgA in the glomerular mesangial areas and capillary walls of
      the high-dose mizoribine-treated ddY mice was markedly decreased as compared with
      that of control ddY mice receiving drinking water. The glomerular mesangial
      expansion in the high-dose mizoribine-treated ddY mice was milder than that found
      in the control ddY mice. In 45-week-old ddY mice, the average number of
      intraglomerular cells in the high-dose and low-dose mizoribine-treated ddY mice
      was slightly lower than that in drinking water treated ddY mice. The levels of
      urinary protein excretion in the high-dose mizoribine-treated ddY mice were also
      lower than those in the low-dose mizoribine-treated or drinking water treated ddY
      mice. It appears that treatment of mizoribine might influence the proliferation
      of B cells, especially IgA-bearing B cells, and improve the glomerular IgA
      deposition and glomerular expansion in early-stage IgA nephropathy of ddY mice.

PMID- 9609466
TI  - A rat model of chemical-induced polycystic kidney disease with multistage tumors.
AB  - Diphenylthiazole (DPT) induces polycystic kidney disease in the rat which serves
      as a model of human acquired cystic disease of the kidney. However, DPT
      administration alone does not produce neoplastic changes in renal cysts. We
      examined the effect of N-nitrosomorpholine (NNM), a carcinogen, in rats bearing
      DPT-induced renal cysts. Forty Sprague-Dawley rats were divided into four groups:
      DPT/NNM, DPT, NNM, and nontreated groups. DPT was administered throughout the
      experimental period, and NNM was given from weeks 4 to 7 after the start of the
      experiment. The rats were sampled from weeks 39 to 48, and histopathological
      examinations of the excised kidneys were performed. Multiple cystic changes were
      observed in all the DPT-treated rats in both DPT and DPT/NNM groups which were
      absent in almost all other rats. Solid adenomatous lesions were observed in the
      NNM-treated rats: in 7 of 9 and in 3 of 10 rats in the DPT/NNM and NNM groups,
      respectively. Cystic adenomatous lesions were found in 4 of 9 rats in the DPT/NNM
      group exclusively and not in the other groups. Combined DPT and NNM
      administration to rats produced an animal model showing neoplastic changes in
      renal cysts resembling microscopically renal cancer lesions in human acquired
      cystic disease of the kidney (on hematoxylin and eosin staining).

PMID- 9609468
TI  - Intercellular adhesion molecule 1 mediates mononuclear cell infiltration into rat
      glomeruli after renal ablation.
AB  - Mononuclear cells, primarily macrophages and lymphocytes, infiltrate the renal
      glomeruli and are involved in the progression of various glomerular diseases.
      Intercellular adhesion molecule 1 (ICAM-1) is expressed on the vascular
      endothelium and mediates the infiltration of leukocytes into the site of
      inflammation. Although the expression of ICAM-1 can be induced by the stimulation
      of inflammatory cytokine, ICAM-1 expression can also be induced by such nonimmune
      mechanisms as shear stress. Glomerular hyperfiltration is a major mechanism that
      contributes to the progression of the glomerular sclerosis that results from the
      loss of functioning nephrons. In the present study, we examined the role of ICAM
      1 for mononuclear cell infiltration in the glomeruli of the five-sixth
      nephrectomized rat as a model of glomerular hyperfiltration. The fluorescence
      intensity score of the staining for ICAM-1 in the glomeruli of the five-sixth
      nephrectomized rats was significantly increased as compared with that in the
      control (sham-operated) rats at 1 week (1.51 +/- 0.15 vs. 0.61 +/- 0.13; p <
      0.01) and 2 weeks (1.31 +/- 0.17 vs. 0.51 +/- 0.09; p < 0.01). The number of
      leukocytes present in the glomeruli was significantly increased in the five-sixth
      nephrectomized rats compared with control (sham-operated) rats at 1 week (3.44 +/
      0.16 vs. 0.99 +/- 0.08; p < 0.01) and 2 weeks (3.14 +/- 0.14 vs. 0.89 +/- 0.07;
      p < 0.01). Leukocytes mainly consisted of macrophages in the five-sixth
      nephrectomized rats at 1 week (2.39 +/- 0.19) and 2 weeks (1.46 +/- 0.11). Anti
      ICAM-1 monoclonal antibody effectively prevented the infiltration of macrophages
      into the glomeruli following nephrectomy. These results indicate that glomerular
      hyperfiltration may be involved in the induction of the expression of ICAM-1 and
      the infiltration of macrophages into the renal glomeruli following glomerular
      injury.

PMID- 9609467
TI  - Purification, characterization and differentiation-dependent expression of a
      perchloric acid soluble protein from rat kidney.
AB  - We have recently reported the presence of a novel perchloric acid soluble protein
      in rat liver (PSP1) that inhibits cell-free protein synthesis in a rabbit
      reticulocyte system. While studying the perchloric acid soluble proteins from
      different tissues of rats, we found that the kidney protein cross-reacted with
      antibody against the PSP1. In this investigation, we have purified a perchloric
      acid soluble protein from the rat kidney and studied its characterization and
      expression. The protein extracted from the postmitochondrial supernatant fraction
      with 5% perchloric acid was purified by ammonium sulfate fractionation and CM
      Sephadex chromatography. By immunoscreening with the rabbit antisera against the
      PSP1, we detected a cDNA that contained an open reading frame of 411 bp, encoding
      a 137 amino-acid protein with a molecular mass of 14,149 daltons. The deduced
      amino acid sequence was completely identical with that of PSP1 from rat liver.
      The perchloric acid soluble protein from rat kidney (K-PSP1) also inhibited cell
      free protein synthesis in the rabbit reticulocyte lysate system in a different
      manner than RNase A. Immunohistochemistry showed that the expression of K-PSP1
      increased from fetal 17th day to postnatal 4th week, and it remained almost the
      same until the 7th week of postnatal age. Furthermore, the expression of K-PSP1
      in the kidney of the nephrotic rat model was shown to be differentiation
      dependent. On the other hand, the expression of K-PSP1 in renal tumor cells was
      downregulated as compared with intact tissue. These results suggest that the
      expression of K-PSP1 is regulated in a differentiation-dependent manner in the
      kidney.

PMID- 9609469
TI  - Effect of dialysate buffer on serum beta-2-microglobulin levels in chronic
      hemodialysis.

PMID- 9609470
TI  - Effectiveness and safety of azithromycin on the treatment of cyclosporine-induced
      gingival overgrowth.

PMID- 9609471
TI  - Suppressed parathyroid hormone response to oral and intravenous calcium
      calcitriol treatment in chronic renal failure.

PMID- 9609472
TI  - Musical hallucinations after childbirth in a female patient on hemodialysis.

PMID- 9609473
TI  - Technical aspects of percutaneous renal biopsy now.

PMID- 9609474
TI  - Renal cell carcinoma presenting as solitary cervical node metastasis compressing
      the brachial plexus.

PMID- 9609475
TI  - Persistent hypercalcemia leading to acute pancreatitis in a patient with relapsed
      myeloma and renal failure.

PMID- 9609476
TI  - Effects of moderate chronic renal failure in aluminum and phosphate excretion.

PMID- 9609477
TI  - Hematuria in nephroptosis.

PMID- 9609478
TI  - Severe eosinophilia related with lansoprazole in a hemodialysis patient.

PMID- 9609479
TI  - Rhinocerebral mucormycosis in a kidney transplant recipient.

PMID- 9609480
TI  - Recurrent pulmonary oedema caused by iliac artery stenosis in a renal transplant
      recipient.

PMID- 9609481
TI  - Altered red blood cell rheology as a predisposing factor for diabetic
      nephropathy.

PMID- 9609482
TI  - A self-administered quality of life questionnaire for renal transplant
      recipients.

PMID- 9609483
TI  - Computer-assisted myocardial thickening analysis of gated MIBI SPECT images.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study is to use the relationship
      between the partial volume effect, count density, matrix size, and reconstruction
      filter in gated single photon emission computer tomography (SPECT) to recover
      myocardial thickness, and to validate measurements generated using a computer
      assisted automatic contour method with a phantom model and with thickness changes
      measured by echocardiography. METHODS: Regional myocardial contour was defined
      automatically using shape constraints, gray level thresholding, and a gradient
      method applied to gated technetium-99m (99mTc)-methoxy-isobutyl-isonitile (MIBI)
      SPECT images. A heart phantom with wall thickness ranging from 0.8 cm to 1.3 cm
      was constructed. SPECT images were acquired and reconstructed using different
      matrix sizes, count densities, and filters. Wall thickness determinations derived
      from the reconstructions made with each combination of matrix size, type of
      filter, and cutoff frequency were correlated with the measured thicknesses. The
      best combination was applied to the gated MIBI SPECT images of 55 patients who
      also had echocardiography and coronary arteriography. Count density measurements
      were made across each regional myocardial segment to evaluate wall thickness at
      end-diastole and end-systole. Systolic wall thickening measurements made with
      this automated computer-assisted contour technique were compared with
      echocardiographic measurements made from segments with normal perfusion and from
      regions containing infarcted tissue. RESULTS: Different reconstruction filters
      and cutoff frequencies affected the accuracy of measurements of myocardial wall
      thickness determined from gated myocardial SPECT images. A matrix size of 64 x
      64, with a minimum of 10 counts/pixel/frame, and use of a Hanning filter with 0.5
      cyc/cm cutoff frequency gave the best combination for myocardial thickness
      determination and spatial resolution. Application of these factors to the phantom
      yielded results that correlated very well with the thickness measurements (r =
      0.986, P < 0.001). Application of the technique to the clinical SPECT studies
      yielded measurements of myocardial wall thickening that were not significantly
      different from that determined by echocardiography. CONCLUSION: Computer-assisted
      contour analysis of gated SPECT images enables accurate determination of regional
      wall thickening using the count density changes within each myocardial segment.

PMID- 9609484
TI  - Evaluation of standard and high-dose contrast-enhanced breath-hold liver magnetic
      resonance for visualization of metastatic disease in an animal model.
AB  - RATIONALE AND OBJECTIVES: The ability of dynamic contrast-enhanced magnetic
      resonance imaging to improve detection of liver metastases was evaluated in an
      experimental rabbit model. Scans using two different contrast doses, 0.1 and 0.3
      mmol/kg, of a gadolinium chelate with extracellular distribution were compared to
      precontrast T2- and T1-weighted scans. METHODS: Seven New Zealand White rabbits
      with VX-2 adenocarcinoma metastases to the liver were imaged at 1.5 tesla. Each
      animal was studied twice, on different days, to evaluate both contrast doses.
      Precontrast T2- and T1-weighted scans were compared to dynamic postcontrast T1
      weighted scans obtained at 1, 2, 3, 4, and 5 minutes after intravenous injection.
      All scans were acquired during suspended respiration. The contrast agent, Gd HP
      DO3A (gadoteridol or ProHance), was administered as a bolus. Images were analyzed
      by region of interest measurements. RESULTS: Injection of 0.3 mmol/kg Gd HP-DO3A
      produced liver enhancement which was statistically superior to 0.1 mmol/kg at all
      time points postcontrast. Enhancement of the paraspinous musculature at the
      higher dose was also statistically superior at all time points, with one
      exception (5 minutes postcontrast). Lesion detectability, evaluated by the signal
      difference over noise ratio, peaked at one minute postcontrast and was
      substantially greater at the higher contrast dose (31.4 +/- 8.3 at 0.3 mmol/kg
      versus 16.8 +/- 4.2 at 0.1 mmol/kg, P = 0.02). CONCLUSIONS: Using a rabbit model
      and breath-hold imaging technique, metastatic lesions in the liver were best
      visualized on early (1 minute) dynamic high dose (0.3 mmol/kg) postcontrast
      scans. Contrast dose and timing of image acquisition are critical issues for
      optimal liver lesion detection on magnetic resonance imaging.

PMID- 9609485
TI  - Synergistic effects of relaxation and susceptibility in differentiation between
      compartmentalized and noncompartmentalized tissues.
AB  - RATIONALE AND OBJECTIVES: This study illustrates the synergistic effects of
      relaxation- and susceptibility-based contrast enhancement. Using a combination of
      gadolinium (Gd) and dysprosium (Dy) complexes and a sequence capable of taking
      advantage of the particular relaxation behavior of this combination, the
      difference between compartmentalized and noncompartmentalized regions was
      significantly enhanced. METHODS: Magnetic resonance imaging of the rat kidney was
      performed before and immediately after the administration of a combination of Gd
      and Dy chelates (Gd-DTPA-BMA and Dy-DTPA-BMA). RESULTS: The signal intensity (SI)
      of the renal parenchyma was reduced by 85%, whereas the collecting tubes had a
      100% increase of their SI as demonstrated by a short repetition time (600 msec),
      long echo time (50 msec), and spin-echo sequence. CONCLUSIONS: The high R2*
      effect, specific to the compartmentalized tissues, associated with the moderately
      high R1 and R2 developed in the remaining areas, results in an important
      improvement in tissue differentiation, which potentially is useful for the
      evaluation of pathological changes as in tubular necrosis.

PMID- 9609486
TI  - Wrist arthrography after acute trauma to the distal radius: diagnostic accuracy,
      technique, and sources of diagnostic errors.
AB  - RATIONALE AND OBJECTIVES: The objective of this investigation was to determine
      the diagnostic accuracy of wrist arthrography in the detection of interosseous
      ligament disruptions and of triangular fibrocartilage complex (TFCC) lesions in
      patients after acute wrist trauma and to define the sources of diagnostic error
      of wrist arthrography after recent trauma. METHODS: Twenty-two patients with
      radial fractures after acute wrist trauma underwent arthrography and arthroscopy
      of the wrist. Arthrography was performed in a standardized manner by two- or
      three-compartment injection technique. Subsequently wrist arthroscopy was
      performed within the same session. Image analysis included the evaluation of
      interosseous carpal ligaments, the TFCC, and the osseous structures. RESULTS: In
      22 patients, 11 injuries of the intrinsic ligaments and the TFCC were diagnosed
      by arthroscopy, of which 9 had been diagnosed correctly with arthrography before
      surgery. One scaphoid fracture previously missed on conventional radiographs also
      could be diagnosed by arthrography. CONCLUSION: Arthrography of the posttraumatic
      wrist is a valuable tool in the diagnostic evaluation of interosseous carpal
      ligaments and the TFCC.

PMID- 9609487
TI  - Exacerbated pain in cervical radiculopathy at axial rotation, flexion, extension,
      and coupled motions of the cervical spine: evaluation by kinematic magnetic
      resonance imaging.
AB  - RATIONALE AND OBJECTIVES: The authors evaluate the functional changes in patients
      with cervical radiculopathy and increasing symptoms after provocative maneuvers
      at flexion, extension, axial rotation, and coupled motions of the cervical spine.
      METHODS: Twenty-one patients with cervical disc herniation (n = 17) or cervical
      spondylosis (n = 4) in whom symptoms were elicited at flexion, extension, axial
      rotation, and coupled motions of the cervical spine were studied. The patients
      were examined inside a positioning device by using a circular surface coil for
      signal reception. At neutral position (0 degrees) and at provocative positions
      sagittal T2-weighted turbo spin-echo, axial T2-weighted two-dimensional flash
      sequence, sagittal three-dimensional (3D) fast imaging with steady state
      precision sequence and coronal 3D double-echo-in-the-steady-state sequences were
      obtained. The 3D sequences were reformatted in the axial and oblique coronal
      planes perpendicular to the exiting nerve roots. The images were evaluated for
      the size of disc herniations, the foraminal size and cervical cord rotation or
      displacement at provocative position compared with neutral position (0 degrees).
      RESULTS: Compared with neutral position (0 degrees), change in size of disc
      herniation was not found in any (0%) of the provocative positions. In five (24%)
      patients cervical cord rotation or displacement was noted at axial rotation. The
      foraminal size increased at flexion, axial rotation to the opposite side of pain
      and flexion combined with axial rotation to the opposite side of the pain. The
      foraminal size decreased at extension combined with axial rotation to the side of
      the pain. A decrease or no change in foraminal size was observed at either
      extension or axial rotation to the side of the pain. CONCLUSIONS: In patients
      with cervical disc herniation or cervical spondylosis, exacerbated pain at
      defined provocative maneuvers is related more to changes in the foraminal size
      and to nerve root motion with, in some cases, cervical cord rotation or
      displacement than to changes in the size of herniated discs.

PMID- 9609488
TI  - Measurement of localized cartilage volume and thickness of human knee joints by
      computer analysis of three-dimensional magnetic resonance images.
AB  - RATIONALE AND OBJECTIVES: This work demonstrates a new method for computerized
      measurement of the dimensions (thickness and volume) of articular cartilage for
      any specified region of the human knee joint. Three-dimensional magnetic
      resonance (MR) images optimized for cartilage contrast have been analyzed using
      computerized edge-detection techniques, and the reproducibility of articular
      cartilage thickness and volume measurements is assessed. METHODS: A fat
      suppressed, three-dimensional SPoiled GRass MR sequence (45/7.5/30 degrees) with
      total scan time of approximately 12 minutes was used to acquire volume images of
      human knee joints at spatial resolution of 0.6 x 1.2 x 1.2 mm. Measurements were
      made using six repeated scans for three healthy volunteers over a period of 2
      months. The subsequent semi-automated image processing to establish total
      cartilage volume and cartilage thickness maps for the femur required
      approximately 60 minutes of operator time. RESULTS: The mean coefficient of
      variation for total cartilage volume for the six repeated scans for the three
      volunteers was 3.8%, and the average coefficient of variation for the user
      selected cartilage plugs was 2.0%. The cartilage thickness maps from the repeated
      scans of the same knee were similar. CONCLUSIONS: Standard resolution MR images
      with fat-suppressed contrast lead to an objective and reproducible measurement of
      spatial dimensions of articular cartilage when analyzed semi-automatically using
      computerized edge-detection methods.

PMID- 9609489
TI  - Evaluation of the effects of high dose irradiation on canine thigh muscle by
      follow-up magnetic resonance imaging and phosphorus-31 magnetic resonance
      spectroscopy.
AB  - RATIONALE AND OBJECTIVES: The authors investigate alterations of proton T1 and T2
      relaxation times and phosphorus metabolites of canine thigh muscle tissue after
      high dose x-ray irradiation by follow-up magnetic resonance imaging (MRI) and
      phosphorus-31 (31P) magnetic resonance spectroscopy (MRS). METHODS: A group of 20
      dogs was used for MRI and in vivo 31P MRS. Single doses of 5,000 and 10,000 cGy
      were delivered to the right thigh muscle of groups of 10 dogs each. All MRI and
      31P MRS examinations were performed before irradiation and 1, 7, 14, 28, 42, and
      56 days after irradiation. For measurement of T1, repetition time (TR) was
      measured at 300, 500, 1000, 1500, 2000 msec and echo time (TE) was fixed at 12
      msec. Also, for measurement of T2, TE was measured at 20, 40, 60, and 80 msec and
      TR was fixed at 2000 msec. Image selected in vivo spectroscopy (ISIS) pulse
      sequence was used to obtain 31P MR spectra. Peak areas for each phosphorus
      metabolite were measured using a Marquart algorithm. RESULTS: Magnetic resonance
      imaging signal began to change at 28 days after a single dose of 10,000 cGy,
      whereas there was no significant MRI signal change until 56 days after a single
      dose of 5,000 cGy. Also, extensive MRI signal changes were observed at 42 days
      after a single dose of 10,000 cGy. Significant correlation was established
      between T2 and a lapse of time although there was no correlation between T1 and a
      lapse of time. T2 value increased substantially corresponding to the time period
      after x-ray irradiation. Although MR spectral change was not observed until 42
      days after a single dose of 5,000 cGy, it began at 14 days after a single dose of
      10,000 cGy. And, significant MR spectral changes were observed at 28 and 42 days.
      Inorganic phosphate and phosphodiesters signal intensities increased while
      phosphocreatine signal intensity decreased. The pH value was 7.22 +/- 0.05 at
      control, and 6.98 +/- 0.04 at 42 days after a single dose of 10,000 cGy.
      CONCLUSIONS: The postirradiation follow-up MRI and 31P MRS studies demonstrated
      that morphologic and metabolic changes were dependent upon the x-ray dose and a
      lapse of time.

PMID- 9609490
TI  - The effect of some iodinated contrast media on human plasma butyrylcholinesterase
      activity.
AB  - The effect of three iodinated contrast media (CM) on human plasma
      butyrylcholinesterase (BuChE) activity was studied during the intravenous
      pyelography (i.v.P). BuChE is an enzyme that participates in the metabolism of
      acetylcholine and hydrolyzes food esters and drugs such as nondepolarizing muscle
      relaxants and local anesthetics. The three CM were: diatrizoate (an ionic
      substance) and iohexol and iopentol (two nonionic substances). Five minutes after
      the intravenous injection, iohexol reduces BuChE plasma activity by 8.5% but this
      effect disappears within 15 minutes. Diatrizoate and iopentol decrease BuChE
      plasma activity by 8% and 15.2%, respectively, 5 minutes after the injection and
      this effect remains stable for the next 15 minutes. The underlying mechanism is
      unknown. Plasma BuChE activity remains within the normal range in any case and no
      association with side effects can be made. Thus, according to the above findings,
      it is not possible to connect or exclude any relationship between BuChE plasma
      activity and CM-derived adverse reactions during the i.v.P.

PMID- 9609491
TI  - Implementing clinical guidelines: how can informatics help?
AB  - Clinical guidelines are heralded as a positive contribution to improving quality
      of care and ensuring the effectiveness of care. From the perspective of the
      health services researcher, the authors propose a model of how informatics can
      support the implementation of clinical guidelines and their integration into
      systems for decision support and clinical audit. Each element of the model is
      discussed in turn.

PMID- 9609492
TI  - Online practice guidelines: issues, obstacles, and future prospects.
AB  - The "guidelines movement" was formed to reduce variability in practice, control
      costs, and improve patient care outcomes. Yet the overall impact on practice and
      outcomes has been disappointing. Evidence demonstrates that the most effective
      method of stimulating awareness of and compliance with best practices is computer
      generated reminders provided at the point of care. This paper reviews five steps
      along the path from the development of a guideline to its integration into
      practice and the subsequent evaluation of its impact on practice and outcomes.
      Issues arising at each step and obstacles to moving from one step to the next are
      described. Last, developments that could help overcome the obstacles are
      highlighted. These include 1) more rapid knowledge acquisition using data mining,
      2) better accommodation to imprecise knowledge in clinical algorithms using fuzzy
      logic, 3) development of a shareable model for guideline representation and
      execution, and 4) more widespread availability of clinically robust information
      systems that support decision-making at the point of care.

PMID- 9609493
TI  - A template-based approach to support utilization of clinical practice guidelines
      within an electronic health record.
AB  - Practice guidelines are an integral part of evidence-based health care delivery.
      When the authors decided to install the clinical documentation component of an
      electronic health record in a nurse practitioner faculty practice, however, they
      found that they lacked the resources to integrate it immediately with other
      systems and components that would support the processing of clinical rules. They
      were thus challenged to devise an initial approach for decision support related
      to clinical practice guidelines that did not include interfacing with an
      inference engine and set of decision rules. The authors developed a prototypic
      application within the WAVE electronic health record that demonstrates the
      feasibility of representing a guideline as structured encoded text organized into
      an online patient-encounter template. Although this approach may be more broadly
      applicable, it is described within the context of the management of diabetes
      mellitus by nurse practitioners. The advantages of the approach relate primarily
      to the integration of the guideline recommendations with the encounter form, the
      online interaction of the clinician with the system, and the ease of creation and
      modification of the guideline-based encounter form. However, there are several
      limitations of the current approach as a result of the inability to do inference
      and the lack of integration with patient-specific data to trigger specific rules.

PMID- 9609495
TI  - Improving health care by understanding patient preferences: the role of computer
      technology.
AB  - If nurses, physicians, and health care planners knew more about patients' health
      related preferences, care would most likely be cheaper, more effective, and
      closer to the individuals' desires. In order for patient preferences to be
      effectively used in the delivery of health care, it is important that patients be
      able to formulate and express preferences, that these judgments be made known to
      the clinician at the time of care, and that these statements meaningfully inform
      care activities. Decision theory and health informatics offer promising
      strategies for eliciting subjective values and making them accessible in a
      clinical encounter in a manner that drives health choices. Computer-based
      elicitation and reporting tools are proving acceptable to patients and clinicians
      alike. It is time for the informatics community to turn their attention toward
      building computer-based applications that support clinicians in the complex
      cognitive process of integrating patient preferences with scientific knowledge,
      clinical practice guidelines, and the realities of contemporary health care.

PMID- 9609494
TI  - The use of multimedia in the informed consent process.
AB  - OBJECTIVE: The goal of the project was to create recommendations and design
      specifications for a multimedia tool to enhance the informed consent process for
      clinical trials. The authors focused on the needs of patients with potential
      cognitive impairment. DESIGN: The authors first performed a needs assessment
      using focus groups and interviews with health care researchers, institutional
      review board members, and three groups of patients (who had depression, breast
      cancer, or schizophrenia). Their feedback was incorporated into the design of a
      prototype multimedia tool. The design included general modules with information
      about clinical trials and informed consent as well as trial-specific modules. The
      authors then used the resulting prototype multimedia tool for informed consent in
      follow-up focus groups and interviews to obtain feedback on the feasibility and
      potential effectiveness of using such a tool routinely for clinical trials.
      RESULTS: The authors showed that it was feasible to adapt a structured multimedia
      informed consent system to a specific clinical trial and to incorporate
      techniques to improve the understandability of informed consent content. Patients
      generally felt the prototype system was useful and could replace the paper
      document. They felt using the system would be less stressful, because they would
      have a greater sense of control and could proceed at their own pace. They liked
      the hierarchic and modular approach to providing information and felt that the
      use of video made information more understandable. Researchers and institutional
      review board members also found the system to be valuable in these ways but had
      concerns about how to review the system for potential biases in presentation and
      about the legal issues associated with replacing the paper document.

PMID- 9609496
TI  - The challenge of meeting patients' needs with a national nursing informatics
      agenda.
AB  - Information has become a capital good and is focused on outcomes. Clinical
      guidelines are being developed to standardize care for populations, but patient
      preferences also need to be known when planning individualized care. Information
      technologies can be used to retrieve both types of information. The concern is
      that nurses are not adequately prepared to manage information using technology.
      This paper presents five strategic directions recommended by the National
      Advisory Council on Nurse Education and Practice (Department of Health and Human
      Services, Division of Nursing) to enhance nurses' preparation to use and develop
      information technology. The recommendations are 1) to include core informatics
      content in nursing curricula, 2) to prepare nurses with specialized skills in
      informatics, 3) to enhance nursing practice and education through informatics
      projects, 4) to prepare nursing faculty in informatics, and 5) to increase
      collaborative efforts in nursing informatics. The potential impact of these
      strategic directions on patients is discussed.

PMID- 9609497
TI  - Infrastructure for reaching disadvantaged consumers: telecommunications in rural
      and remote nursing in Australia.
AB  - Both consumers and health service providers need access to up-to-date
      information, including patient and practice guidelines, that allows them to make
      decisions in partnership about individual and public health in line with the
      primary health care model of health service delivery. Only then is it possible
      for patient preferences to be considered while the health of the general
      population is improved. The Commonwealth Government of Australia has allocated
      $250 million over five years, starting July 1, 1997, to support activities and
      projects designed to meet a range of telecommunication needs in regional, rural,
      and remote Australia. This paper defines rural and remote communities, then
      reviews rural and remote health services, information, and telecommunication
      technology infrastructures and their use in Australia to establish the current
      state of access to information tools by rural and remote communities and rural
      health workers in Australia today. It is argued that a suitable telecommunication
      infrastructure is needed to reach disadvantaged persons in extremely remote areas
      and that intersectoral support is essential to build this infrastructure. In
      addition, education will make its utilization possible.

PMID- 9609498
TI  - Development of the Logical Observation Identifier Names and Codes (LOINC)
      vocabulary.
AB  - The LOINC (Logical Observation Identifier Names and Codes) vocabulary is a set of
      more than 10,000 names and codes developed for use as observation identifiers in
      standardized messages exchanged between clinical computer systems. The goal of
      the study was to create universal names and codes for clinical observations that
      could be used by all clinical information systems. The LOINC names are structured
      to facilitate rapid matching, either automated or manual, between local
      vocabularies and the universal LOINC codes. If LOINC codes are used in clinical
      messages, each system participating in data exchange needs to match its local
      vocabulary to the standard vocabulary only once. This will reduce both the time
      and cost of implementing standardized interfaces. The history of the development
      of the LOINC vocabulary and the methodology used in its creation are described.

PMID- 9609499
TI  - How should we organize to do informatics? Report of the ACMI Debate at the 1997
      AMIA Fall Symposium.

PMID- 9609501
TI  - Nursing Informatics 1997 postconference on patient guidelines and clinical
      practice guidelines: the state of our knowledge and a vision.

PMID- 9609500
TI  - Identifying adverse drug events: development of a computer-based monitor and
      comparison with chart review and stimulated voluntary report.
AB  - BACKGROUND: Adverse drug events (ADEs) are both common and costly. Most hospitals
      identify ADEs using spontaneous reporting, but this approach lacks sensitivity;
      chart review identifies more events but is expensive. Computer-based approaches
      to ADE identification appear promising, but they have not been directly compared
      with chart review and they are not widely used. OBJECTIVES: To develop a computer
      based ADE monitor, and to compare the rate and type of ADEs found with the
      monitor with those discovered by chart review and by stimulated voluntary report.
      DESIGN: Prospective cohort study in one tertiary-care hospital. PARTICIPANTS: All
      patients admitted to nine medical and surgical units in a tertiary-care hospital
      over an eight-month period. MAIN OUTCOME MEASURE: Adverse drug events identified
      by the computer-based monitor, by chart review, and by stimulated voluntary
      report. METHODS: A computer-based monitoring program identified alerts, which
      were situations suggesting that an ADE might be present (e.g., an order for an
      antidote such as naloxone). A trained reviewer then examined patients' hospital
      records to determine whether an ADE had occurred. The results of the computer
      based monitoring strategy were compared with two other ADE detection strategies:
      intensive chart review and stimulated voluntary report by nurses and pharmacists.
      The monitor and the chart review strategies were independent, and the reviewers
      were blinded. RESULTS: The computer monitoring strategy identified 2,620 alerts,
      of which 275 were determined to be ADEs. The chart review found 398 ADEs, whereas
      voluntary report detected 23. Of the 617 ADEs detected by at least one method, 76
      ADEs were detected by both computer monitor and chart review. The computer
      monitor identified 45 percent; chart review, 65 percent; and voluntary report, 4
      percent. The ADEs identified by computer monitor were more likely to be
      classified as "severe" than were those identified by chart review (51 versus 42
      percent, p = .04). The positive predictive value of computer-generated alerts was
      16 percent during the first eight weeks of the study; rule modifications
      increased this to 23 percent in the final eight weeks. The computer strategy
      required 11 person-hours per week to execute, whereas chart review required 55
      person-hours per week and voluntary report strategy required 5. CONCLUSIONS: The
      computer-based monitor identified fewer ADEs than did chart review but many more
      ADEs than did stimulated voluntary report. The overlap among the ADEs identified
      using different methods was small, suggesting that the incidence of ADEs may be
      higher than previously reported and that different detection methods capture
      different events. The computer-based monitoring system represents an efficient
      approach for measuring ADE frequency and gauging the effectiveness of ADE
      prevention programs.

PMID- 9609502
TI  - Knowing what to do: international perspectives on the roles of clinical
      guidelines and patient preferences in patient care.

PMID- 9609503
TI  - Assuring the production of scholars who will continue to build nursing knowledge
      into the next millenium.

PMID- 9609504
TI  - Imaging ability and effective use of guided imagery.
AB  - Imaging ability, the ability to generate mental images and become absorbed in
      them as if they were real, is proposed as a moderator in the relationship between
      guided imagery and symptom relief. Two existing measures of image generation,
      Marks's (1973) Vividness of Visual Imagery Questionnaire and Betts's (1909)
      shortened Questionnaire Upon Mental Imagery (Sheehan, 1967), and one measure of
      absorption, Tellegen's Absorption scale (1993; TAS) were completed by 60 graduate
      students prior to listening to a guided imagery intervention to relieve anxiety
      associated with an upcoming stressful task. Analyses were conducted using data
      from 30 participants (7 men and 23 women) who reported an increase in anxiety
      level after learning of the stressful task. Participants were divided into two
      groups, successful (n=21) and unsuccessful (n=9) users of imagery, based on
      change in anxiety scores after listening to the guided imagery intervention.
      Absorption (TAS) scores were significantly higher for persons in the successful
      group; there were no differences in image generation scores. Two TAS items were
      identified as potential predictors of success with guided imagery. Findings may
      be helpful in developing a clinically useful instrument to predict likelihood of
      success with guided imagery in relieving cancer pain and its distress.

PMID- 9609505
TI  - The long-term efficacy of a behavioral parent training intervention for families
      with 2-year-olds.
AB  - The effectiveness of a behavioral parent training (BPT) intervention for
      improving maternal self-efficacy, maternal stress, and the quality of mother
      toddler interactions has been demonstrated (Gross, Fogg, & Tucker, 1995). The 1
      year follow-up of the 46 parents of toddlers (assigned to an intervention or
      comparison group) who participated in that study is reported. It was hypothesized
      that (a) BPT would lead to enduring positive changes in parenting self-efficacy,
      parenting stress, and parent-toddler interactions; and (b) the amount of parent
      participation in the intervention would be correlated with greater gains in
      parent-child outcomes at 1 year. All the families were retained and significant
      gains in maternal self-efficacy, maternal stress, and mother-child interactions
      were maintained. Minimal BPT effects were found for fathers. BPT dosage was
      related to reductions in mother critical statements and negative physical
      behaviors at 1-year postintervention. The findings are consistent with self
      efficacy theory and support parenting self-efficacy as a target for BPT in
      families of young children.

PMID- 9609506
TI  - The Prenatal Psychosocial Profile: a research and clinical tool.
AB  - This report summarizes five studies of culturally diverse women who were
      administered the Prenatal Psychosocial Profile (PPP). These data from 3,444 rural
      and urban women of all childbearing ages support the validity and reliability of
      the PPP as a measure of stress, support from partner, and support from others.
      The self-esteem scale is a valid and reliable measure for Caucasian and African
      American women. However, the cultural appropriateness of the self-esteem scale
      for Native American women is questionable, and it is neither valid nor culturally
      appropriate for traditional Hispanic women. The mean scores for stress, partner
      support, and other support were similar for all groups except for scales expected
      to differ by sample groups. Thus, suggested cutoff scores should be useful for
      screening purposes. The PPP provides a brief, yet comprehensive profile that is
      accepted by participants and useful to researchers and clinicians.

PMID- 9609507
TI  - Estrogen suppresses gastric motility response to thyrotropin-releasing hormone
      and stress in awake rats.
AB  - Symptoms associated with gastric motility alteration vary with stress and ovarian
      hormone status, most notably in women with irritable bowel syndrome. This study
      examines combined effects, comparing gastric motility during administration of a
      stress-related neuropeptide thyrotropin-releasing hormone (TRH) and restraint
      stress in conscious rats of varied ovarian hormone status. Adult rats were
      ovariectomized and implanted with estrogen, progesterone, or vehicle-releasing
      pellets. After 21 days, intracerebroventricular (i.c.) cannula and gastric
      tension transducer were implanted. After 25-27 days, motility was recorded during
      neuropeptide injection (TRH/saline i.c.) or restraint stress. TRH induced
      increased motility in all groups; the response varied with hormone group, and was
      least and briefest in estrogen-treated rats. Motility during restraint varied
      with hormone group; it was diminished in estrogen-treated but not other groups.
      Ovarian hormone status (estrogen) modifies gut response to TRH and restraint
      stress.

PMID- 9609508
TI  - Age and extent of surgery affect attention in women treated for breast cancer.
AB  - Women treated for breast cancer have shown attentional fatigue manifested as a
      decreased capacity to concentrate or direct attention in daily life activities.
      This study was conducted to determine if age and extent of surgery increase the
      risk of early development of attentional fatigue in 74 women newly diagnosed with
      Stage I or II breast cancer. Measures of capacity to direct attention (CDA) were
      obtained at two time points, about 12 days before, and 15 days after, breast
      conserving surgery or mastectomy. ANOVA showed significant age and age by time
      interaction effects (p < .05). Women aged 65-79 showed a significant mean decline
      (p < .05) in CDA over time regardless of extent of surgery. Women aged 46-64, who
      underwent mastectomy, showed a mean loss in CDA, whereas those having breast
      conserving surgery showed a significant mean gain (p < .05). Women aged 25-45
      showed no significant mean change in CDA over time. Older age and more extensive
      surgery increase the likelihood of loss of attention due, in part, to greater
      risk of attentional fatigue.

PMID- 9609509
TI  - An intervention for changing high-risk HIV behaviors of African American drug
      dependent women.
AB  - The purpose of this study was to test the effectiveness of an AIDS education
      intervention for methadone-dependent, African American women. The women were
      randomly assigned to experimental (n=107) or control (n=97) group. The
      experimental group participated in a peer counseling and leadership training
      program conducted by two experienced nurse counselors over an 8-week period,
      followed by 8 weeks of reinforcement. The program was designed to reduce AIDS
      high-risk sexual behavior, increase self-esteem, decrease depressive affect, and
      increase the women's community-based AIDS prevention communication activities. A
      total of 130 women completed all phases of the study, including longitudinal
      Posttests at 2, 4, and 7 months after enrollment. Compared to the control group,
      there were statistically significant differences in three of the outcomes for the
      experimental group: The experimental group reported an increased number of safer
      sexual behaviors (p=.029), showed decreases in depression (p=.001), and reported
      engaging in more AIDS-related, community-based communication activities regarding
      prevention (p=.005).

PMID- 9609510
TI  - HIV informal caregiving: emergent conflict and growth.
AB  - Findings are reported from a prospective study of 20 persons on the experience of
      providing informal care to partners or family members with HIV syndrome. In
      depth, focused interviews were completed. Data were initially coded using an
      inductive technique and thematically analyzed. The informal care providers were
      found to engage in a variety of interacting, and often conflicting, psychosocial
      and instrumental processes that occurred over three emergent phases: (a)
      transitions to care, (b) living the burden, and (c) facing the void. Although the
      care providers struggled with various sources of uncertainty and distress, when
      periods of equanimity were realized, they experienced a heightened sense of
      coherence and personal growth.

PMID- 9609511
TI  - Finding a balance point: a process central to understanding family caregiving in
      Taiwanese families.
AB  - The grounded theory method was used to explore the psychosocial process of family
      caregiving to frail elders in Taiwan. Interview and observation data from 15
      family caregivers were analyzed using constant comparative analysis. Caregivers
      used the process of finding a balance point to achieve or preserve equilibrium
      between and within caregiving and family life. Caregivers who did better in
      finding a balance point provided better quality care to frail elders. Caregivers
      who were good at finding a balance point anticipated competing needs,
      conceptualized multiple strategies to meet the needs, and predicted accurately
      the consequences of the strategies. They described a wide variety of balancing
      strategies.

PMID- 9609512
TI  - Structural equation modeling and its relationship to multiple regression and
      factor analysis.
AB  - Using a conceptual and nontechnical approach, the meaning of structural equation
      modeling (SEM) and the similarities to, and differences from, more commonly used
      procedures such as correlation, regression, path analysis, and factor analysis
      are explained. Application of the statistical technique is presented using data
      from a study of the relationships among stresses, strains, and physical health in
      a random sample of 492 community-dwelling elders aged 65 and older. Advantages of
      each statistical procedure are described. Theoretical issues related to the use
      of each procedure are presented with emphasis on the need for a sound theoretical
      model and match between the statistical procedure and the aims of the analysis.

PMID- 9609513
TI  - Can haemophilic arthropathy be prevented?

PMID- 9609514
TI  - Ineffective haemopoiesis and apoptosis in myelodysplastic syndromes.

PMID- 9609515
TI  - GM-CSF promotes differentiation of a precursor cell of monocytes and Langerhans
      type dendritic cells from CD34+ haemopoietic progenitor cells.
AB  - Epithelia-associated dendritic cells (DC) including Langerhans cells in the skin
      (LC) are precursors of lymph node located interdigitating DC (iDC). CD1a+ LC are
      known to be derived from CD34+ haemopoietic progenitor cells (HPC); however,
      cells of an intermediate differentiation state that are CD34- and CD1a- have not
      been identified. Monitoring the differentiation pathway of HPC in the presence of
      GM-CSF+IL-4, we observed the emergence of a distinct LC precursor population that
      was CD33+ CD13+ CD4+ CD38+ CD44+ CD34- CD14- CD1a-. The cells could be separated
      by FACS due to a unique CD44/CD38 expression pattern or by CD44 expression in
      conjunction with the SSC profile. It was found that they were similarly generated
      in the presence of GM-CSF alone and were detectable in culture for at least a
      week. Irrespective of being generated in the presence of GM-CSF+IL-4 or GM-CSF
      alone, CD44/SSC-sorted precursor cells matured to MHC class II compartments
      (MIIC) and Birbeck granules (BG) expressing LC, when subsequently cultured in the
      presence of GM-CSF+IL-4. When IL-4 was omitted, however, the same cells matured
      to phagocytically active adherent macrophages (Mphi). These culture conditions
      were associated with a > 4-fold increase in the concentration of IL-6 when
      compared to those used for LC differentiation. The identification of a distinct
      oligopotent precursor cell population that can deliberately be induced to give
      rise to BG+ MIIC+ CD1a+ CD14- LC or to adherent CD14+ Mk further substantiates
      the close relationship of monocytes and DC and may help to identify its in vivo
      equivalent.

PMID- 9609516
TI  - Serum thrombopoietin level is mainly regulated by megakaryocyte mass rather than
      platelet mass in human subjects.
AB  - A patient with idiopathic thrombocytopenic purpura (ITP) developed T-cell
      lymphoma while undergoing steroid therapy. We examined the relationship between
      the patient's serum thrombopoietin (Tpo) level, platelet count, megakaryocyte
      number and CFU-Meg number during the second 5 d course of chemotherapy for
      lymphoma in which megakaryopoiesis switched from ITP phase to amegakaryocytic
      phase. The patient's platelet count was temporarily elevated but CFU-Meg numbers
      were markedly suppressed, and megakaryocyte numbers were decreased in this
      period, whereas serum Tpo level was not suppressed despite an increased platelet
      count, indicating that serum Tpo level is mainly regulated by megakaryocyte mass.

PMID- 9609517
TI  - Evidence that the ubiquitin proteolytic pathway is involved in the degradation of
      precipitated globin chains in thalassaemia.
AB  - Ultrastructural immunocytochemical studies were performed on sections of bone
      marrow from three patients with beta-thalassaemia major and two patients with
      haemoglobin H (HbH) disease. Some sections were reacted with either a polyclonal
      or a monoclonal anti-human-ubiquitin antibody and the reaction visualized using a
      gold-labelled secondary antibody. The inclusions of precipitated globin chains
      found within the erythropoietic cells of all five patients reacted much more
      strongly than the surrounding inclusion-free cytoplasm with both of the anti
      ubiquitin antibodies, indicating that the precipitated globin chains were
      ubiquitinated. A non-specific reaction between the anti-ubiquitin antibodies and
      the inclusions was excluded by demonstrating that various other antibodies,
      including a polyclonal anti-human cathepsin D antibody, did not react with the
      inclusions. The data suggest that the ubiquitin proteolytic pathway is involved
      in the degradation of precipitated globin chains in alpha- and beta-thalassaemia.

PMID- 9609518
TI  - Frequent de novo monoallelic expression of beta-spectrin gene (SPTB) in children
      with hereditary spherocytosis and isolated spectrin deficiency.
AB  - This report represents an attempt to define the rate of beta-spectrin de novo
      mutations affecting mRNA accumulation in patients with hereditary spherocytosis
      (HS). 19 HS children with haematologically normal parents and varying degrees of
      spectrin deficiency were studied. 13 of the 19 cases who were heterozygous at the
      genomic level for polymorphisms in the beta-spectrin coding region were further
      studied. However, in an analysis of reverse-transcripted amplified cDNA from the
      regions of the polymorphisms, seven patients appeared to be homozygous,
      suggesting the occurrence of de novo mutational events affecting expression of
      one beta-spectrin allele. We conclude that in HS patients with isolated spectrin
      reduction and normal parents the apparently recessive pattern of inheritance may
      frequently be associated with de novo monoallelic expression of beta-spectrin.

PMID- 9609519
TI  - Cone and platelet analyser (CPA): a new test for the prediction of bleeding among
      thrombocytopenic patients.
AB  - The risk of bleeding among thrombocytopenic patients was evaluated using our new
      cone and platelet analyser (CPA) test. Using this test, adherence of platelets
      was quantitated on extracellular matrix and expressed as percent of surface
      coverage (SC) and the average size (AS) of aggregates. 42 thrombocytopenic
      patients with ITP (n=23), post chemotherapy (n= 12) and others (n= 7) were tested
      over a total of 82 visits. On each visit, complete blood count and CPA tests were
      performed and patients were evaluated for evidence of bleeding (found in 40
      visits). Bleeding patients had significantly lower platelet counts (27.4 +/- 22.0
      v 47.1 +/- 21.0 x 10(9)/l), lower haematocrit values (30.2 +/- 8.1 v 35.2 +/-
      6.6%), lower MPV (6.83 +/-1.89 v 8.98 +/- 1.13 fl), and lower SC (4.87 +/- 3.95 v
      10.33 +/-5.48%) and AS (33.99 +/- 14.94 v 52.9 +/- 24.34 microm2). Univariate
      analysis yielded platelet count < or =20.0 x 10(9)/l, MPV < or =8 fl, haematocrit
      <35%, SC <5%, AS< or =40 microm2 as significantly associated with bleeding,
      whereas only MPV and SC were associated with bleeding (OR 6.95, CI 2.25-21.46 and
      OR 4.27, CI 1.29-14.16, respectively) by multivariate analysis. When taken
      together, 21/22 of patients (95%) with both low SC (<5%) and low MPV (<8.0 fl)
      had bleeding symptoms, whereas only 9/43 (21%) patients with both these
      parameters above these values experienced bleeding symptoms. We conclude that the
      CPA test and the parameter SC (<5%) together with MPV (< or =8 fl) might be used
      as independent predictors of bleeding in the management of thrombocytopenic
      patients.

PMID- 9609520
TI  - Association between hyperflexibility of the thumb and an unexplained bleeding
      tendency: is it a rule of thumb?
AB  - A bleeding tendency manifested by petechiae and ecchymoses is one of the most
      common causes for referral of patients to haematology clinics. Vessel wall
      pathology is not usually considered to be a cause for deranged haemostasis,
      although coexistence of increased capillary fragility and joint hypermobility
      have been reported. We determined the frequency of thumb hyperextensibility and
      scored the findings in a series of 44 patients referred because of ecchymoses and
      petechiae, as well as 261 control children and their mothers. All 44 patients had
      normal coagulation studies. Thumb flexibility score was +4 in 30 patients, +3 in
      eight patients, +2 in five patients and +1 in one of the index patients. In the
      control group, only one of 261 had a +4, and three had a +3 score, and two of 260
      mothers had a +4 score. Ecchymoses were not observed in any of these subjects,
      nor in the +1 patients. Based on clinical presentation and normal coagulation
      studies, we suggest that our patients had an underlying subtype of Ehlers-Danlos
      syndrome. In view of the dramatically high occurrence of thumb hyperextensibility
      in patients with unexplained mild bleeding tendency, costly haemostatic and
      coagulation studies on such patients may not be necessary.

PMID- 9609521
TI  - Arg260-Cys mutation in severe factor XIII deficiency: conformational change of
      the A subunit is predicted by molecular modelling and mechanics.
AB  - To explore the implications of the structure/ function relationships in factor
      XIII. a patient with severe A subunit deficiency was examined at the DNA and RNA
      levels. Nucleotide sequence analysis of the patient's DNA amplified by PCR
      revealed that the patient had a replacement of C by T in the codon for Arg260. RT
      PCR analysis demonstrated that only one kind of mRNA coding for the Arg260-Cys
      mutation was expressed in the patient at a normal level. Another possible
      defective allele of the A subunit gene with a G-A polymorphism was not expressed
      (null allele). The substitution of Arg260 by Cys located on the interface of two
      A subunits would preclude the reciprocal ionic interaction (salt bridge) between
      Arg260 and Asp404. Molecular modelling and, for the first time, molecular
      mechanics calculated that Cys260 changed the local conformation of the A subunit
      and reduced the electrostatic interaction between two monomers, suggesting
      destabilization of the molecule's dimer.

PMID- 9609522
TI  - Androgen effects on factor IX expression: in-vitro and in-vivo studies in mice.
AB  - A role for steroid hormones has been proposed for the post-pubertal factor IX
      increment of approximately 25% seen in both normal males and females, as well as
      in the post-pubertal phenotypic recovery seen in haemophilia B Leyden. We have
      evaluated androgen receptor binding to the factor IX promoter and have assessed
      transcriptional activation of the factor IX gene in hepatocytes through transient
      transfection studies and through expression of factor IX in a murine model of
      androgen insensitivity. Whereas transfection of the androgen receptor alone did
      not activate expression from the factor IX promoter, co-transfection with the
      CCAAT enhancer binding protein resulted in a synergistic 17-fold enhancement of
      transcriptional activity. Using liver nuclear extracts and recombinant androgen
      receptor protein we have confirmed binding of this protein to the factor IX
      proximal promoter and disruption of binding with a mutation at nucleotide -26.
      Finally, studies in normal and testicular feminized male mice showed different
      developmental patterns of factor IX expression. In normal mice, expression
      recapitulates that seen in humans, with early post-natal levels being
      approximately 50% of the adult values and with a post-pubertal increment of
      approximately 25%. In contrast, testicular feminized animals did not show a
      significant post-pubertal increment of factor IX. These studies provide further
      support for the role of androgen receptor binding to the factor IX promoter in
      regulating the developmental expression of factor IX.

PMID- 9609523
TI  - Failure of oral pamidronate to reduce skeletal morbidity in multiple myeloma: a
      double-blind placebo-controlled trial. Danish-Swedish co-operative study group.
AB  - In order to study whether oral bisphosphonate therapy might prevent or reduce
      skeletal-related morbidity in patients with newly diagnosed multiple myeloma who
      required chemotherapy, 300 patients were included in a randomized multi-centre
      trial. Patients were given oral pamidronate at a dose of 300 mg daily, or
      placebo, in addition to conventional intermittent melphalan/prednisolone (and in
      some cases alpha-interferon) treatment. With a median treatment duration of about
      550d, no statistically significant reduction in skeletal-related morbidity
      (defined as bone fracture, related surgery, vertebral collapse, or increase in
      number and/or size of bone lesions) could be demonstrated. Pamidronate treatment
      also did not have any influence on patient survival or on the frequency of
      hypercalcaemia. However, in patients treated with pamidronate there were fewer
      episodes of severe pain (P=0.02) and a decreased reduction of body height of 1.5
      cm (P= 0.02). The overall negative result of the study is attributed to the very
      low absorption of orally administered bisphosphonates in general.

PMID- 9609524
TI  - Interleukin-6 is expressed by plasma cells from patients with multiple myeloma
      and monoclonal gammopathy of undetermined significance.
AB  - Interleukin-6 (IL-6) is an important growth factor for human myeloma cells in
      vitro and in vivo. However, the identity of the cells producing IL-6 in vivo in
      patients with multiple myeloma (MM) remains the subject of debate. We have
      developed a sensitive dual-colour fluorescence in situ hybridization (FISH)
      technique to investigate the expression of IL-6 mRNA by individual bone marrow
      plasma cells from patients with multiple myeloma, monoclonal gammopathy of
      undetermined significance (MGUS) and healthy subjects. IL-6 mRNA could be
      identified in all immunoglobulin light chain (IgLC) expressing cells from all
      patients with MM and MGUS. The IL-6 protein could also be detected by direct
      immunofluorescence in all plasma cells (cytoplasmic light chain positive) from
      all patients with MM and MGUS. Furthermore, it was also possible to demonstrate
      cytoplasmic IL-6 staining of plasma cells from patients with MM by flow
      cytometric analysis. In contrast, neither the IL-6 mRNA or protein could be
      detected in normal plasma cells from healthy bone marrow donors. These data
      demonstrate that plasma cells from patients with MM and MGUS express the IL-6
      mRNA and synthesize the IL-6 protein and support the hypothesis that autocrine
      synthesis of IL-6 is of importance in patients with MM.

PMID- 9609525
TI  - Multiple myeloma and the translocation t(11;14)(q13;q32): a report on 13 cases.
AB  - Complex cytogenetic abnormalities have been described in patients with multiple
      myeloma (MM). To better understand the significance of the most frequent
      translocation observed in MM, we studied the clinical characteristics of patients
      with MM and the t(11;14)(q13;q32) abnormality. A search of the cytogenetic
      database at the Mayo Clinic identified patients with MM and t(11;14)(q13;q32).
      The medical records were reviewed for the clinical characteristics of these
      patients. We identified 13 patients with MM and t(11;14)(q13;q32) determined by
      standard cytogenetic analysis: in 10 patients the abnormality was detected at the
      time of relapse (three with previously normal results of cytogenetic
      examination). At the time the translocation was detected, plasma cell (PC)
      leukaemia was clinically diagnosed in two patients. The median number of
      circulating PCs, as determined by the cytoplasmic immunofluorescence of T-cell
      depleted peripheral blood mononuclear cells, was 1.1x10(9)/l (mean 1.74; range
      0.0017-6.26x10(9)/l). On linear regression analysis there was a strong
      correlation between the number of circulating PCs and the number of bone marrow
      PCs. The median survival after demonstration of the translocation was 8.1 months.
      Of all patients, 10 died of disease progression and three were alive. Patients
      with MM who have t(11;14)(q13;q32) seem to have an aggressive clinical course,
      even when the abnormality is detected at the time of diagnosis, with evidence of
      many circulating PCs.

PMID- 9609526
TI  - Bone marrow and peripheral blood involvement in mantle cell lymphoma.
AB  - The peripheral blood smears, bone marrow aspirates and biopsies of 46 patients
      with mantle cell lymphoma were reviewed. The diagnosis of mantle cell lymphoma
      was established in all cases on extramedullary tissue samples using standard
      morphologic, phenotypic and molecular genetic criteria. 27/35 patients (77%) had
      circulating lymphoma cells (median 200%m of all circulating white blood cells;
      range 5-90%) identified by morphology at some point during the course of their
      disease. No statistical difference in survival was detected in patients with or
      without peripheral blood involvement. Lymphoma was identified in bone marrow
      aspirate specimens from 33/40 patients (83%) and in bone marrow biopsy specimens
      from 39/43 patients (91%). The pattern of marrow biopsy involvement was nodular
      (31 cases; 82%), interstitial (19 cases; 50%), paratrabecular (17 cases, 45%) and
      diffuse (12 cases; 32%). Although the median survival of patients with > or = 50%
      bone marrow involvement was 13 months, and the median survival of patients with <
      or = 50% was 49 months; no statistically significant differences between these
      small subgroups were observed. Mantle cell lymphoma frequently involves the
      peripheral blood and bone marrow. Its appearance is distinctive but variable, and
      immunophenotypic studies as well as morphologic confirmation by a biopsy of
      tissue other than bone marrow is still required for diagnosis.

PMID- 9609527
TI  - Functional analysis of the p53 protein in AIDS-related non-Hodgkin's lymphomas
      and polymorphic lymphoproliferations.
AB  - Alteration of the tumour suppressor gene p53 is frequent in AIDS-related non
      Hodgkin's lymphomas (AIDS-NHL), particularly in Burkitt's or Burkitt's-like
      lymphomas (BL/BLL). Since mechanisms of inactivation other than mutations have
      been advanced, the transcriptional activity of the p53 protein was studied in a
      functional assay in yeast in a series of AIDS-NHL lesions and compared with their
      morphology, immunohistochemistry (IHC) and single-strand conformation
      polymorphism (SSCP) analysis detection of other p53 abnormalities, Epstein-Barr
      virus (EBV) status, MDM-2 oncoprotein expression and c-MYC rearrangement.
      Polymorphic lymphoproliferations (PL), identified as precursors of NHL in HIV
      patients, were also analysed in attempt to detect p53 modifications related to
      clonal progression. The functional assay detected p53 mutants in 40% (12/ 30) of
      the tumours: 50% (6/12) of BL/BLL, 40% (4/10) of diffuse large cell lymphomas
      (DLCL) and 25% (2/8) of PL. An oligoclonal or monoclonal population was
      identified in the two PL cases with mutant p53. An accumulation of the p53
      protein was detected by IHC in 26% (8/30) of the tumours (five BL/BLL and three
      DLCL) and was associated with positive functional assay. In the 20 lesions tested
      by both of the screening methods for mutations, a p53 mutant pattern was detected
      in 55% of cases (11/20) and in 25% of cases (5/ 20) respectively with the
      functional assay and SSCP analysis of exons 5-8. There was no inverse correlation
      between the detection of EBV genome and the presence of p53 mutations and no
      overexpression of MDM-2 protein for the whole series. In conclusion, the
      functional assay was more sensitive than IHC and SSCP for the detection of p53
      mutations in tumour samples. The mutations identified in AIDS-NHL lesions
      inactivate the p53 protein and in PL they could represent a selection of an
      aggressive clone.

PMID- 9609528
TI  - Epitope mapping of HTLV envelope seroreactivity in LGL leukaemia.
AB  - Sera from approximately 50% of patients with large granular lymphocyte (LGL)
      leukaemia react with a recombinant human T-cell leukaemia/lymphoma virus (HTLV)
      transmembrane envelope protein, p21e. Two immunodominant epitopes within env p21e
      have been defined by reactivity against recombinant proteins GD21 and BA21. In
      this study sera from 41 patients with LGL leukaemia were examined for reactivity
      against these recombinant HTLV env proteins. Overall, 21/41 (51%) sera reacted to
      p21e. Only two sera reacted to GD21. The predominant immunoreactivity against
      p21e was directed against the BA21 epitope, with 19/41 (46%) sera being BA21
      positive. Seroconversion to BA21 protein was also documented. PCR analyses
      confirmed the low incidence of protypical HTLV sequences (2/41, 5%). These data
      document an association between BA21 seroreactivity and LGL leukaemia. This
      finding raises the possibility that such BA21 seroreactivity could be due to
      cross-reactivity to a cellular or retroviral antigen sharing some amino acid
      homology with the transmembrane glycoprotein of HTLV.

PMID- 9609529
TI  - Distinction of eosinophilic leukaemia from idiopathic hypereosinophilic syndrome
      by analysis of Wilms' tumour gene expression.
AB  - In patients presenting with immature eosinophilic precursors it is notoriously
      difficult to distinguish acute eosinophilic leukaemia (EoL) from the benign
      idiopathic hypereosinophilic syndrome (HES), based on morphological, cytochemical
      and immunophenotyping criteria, alone. Cytogenetic analysis or fluorescence in
      situ hybridization (FISH) can help in discriminating between these rare
      haematological disorders, but often treatment decisions cannot wait for the
      results of these time-consuming techniques. Recently, we and others found Wilms'
      tumour (WT1) gene expression to be increased in virtually all patients with acute
      leukaemias, whereas normal haemopoietic progenitors express the WT1 gene at much
      lower levels or not at all. To determine whether detection of WT1 gene expression
      is useful to distinguish EoL from HES patients, we analysed, by RT-PCR, bone
      marrow or blood mononuclear cells from EoL (n=3), HES (n=3) and reactive
      eosinophilia patients (n = 4) for WT1 gene expression. Using our WT1-RT-PCR
      protocol, we found WT1 gene expression to be restricted to EoL patients. By
      detecting WT1 mRNA transcripts in the cerebrospinal fluid using RT-PCR, we were
      also able to diagnose isolated CNS-relapsed leukaemia, initially confused with
      bacterial meningitis, in an EoL patient. In conclusion, we show that WT1-RT-PCR
      is a powerful complementary diagnostic tool to distinguish acute eosinophilic
      leukaemia from the hypereosinophilic syndromes. This observation needs
      confirmation in a larger series of EoL and HES patients.

PMID- 9609530
TI  - Clonal T-cell proliferation causing pure red cell aplasia in chronic B-cell
      lymphocytic leukaemia: successful treatment with cyclosporine following in vitro
      abrogation of erythroid colony-suppressing activity.
AB  - Clonal T cells that cause pure red cell aplasia were demonstrated in a patient
      with chronic B-cell lymphocytic leukaemia. The T-cell fraction was enriched by
      the immunomagnetic method and shown to have T-cell receptor-beta gene
      rearrangement. Cryopreserved T cells, obtained during the period of anaemia,
      suppressed autologous erythroid progenitor cell growth from remission marrow. The
      colony-suppressing activity was markedly improved by the addition of cyclosporine
      to the culture medium. The patient achieved haematological remission by
      cyclosporine monotherapy. Cyclosporine treatment may improve erythropoiesis in
      both a T-cell-dependent and a T-cell-independent manner.

PMID- 9609531
TI  - A study to determine whether trisomy 8, deleted 9q and trisomy 22 are markers of
      cryptic rearrangements of PML/RARalpha, AML1/ETO and CBFB/MYH11 respectively in
      acute myeloid leukaemia. MRC Adult Leukaemia Working Party. Medical Research
      Council.
AB  - Acute myeloid leukaemia (AML) patients with either a t(15;17), t(8;21) or inv(16)
      at diagnosis have 'good-risk' disease with a favourable response to therapy and
      improved survival. Detection of cryptic fusion genes created by these
      translocations has been reported where there is no cytogenetic evidence of the
      corresponding abnormality. It is likely that these cases share the same
      favourable prognosis. Secondary cytogenetic changes commonly associated with
      these rearrangements are +8 with t(15;17), del(9q) with t(8;21) and +22 with
      inv(16). These secondary abnormalities are also observed alone, raising the
      possibility that they may be markers of underlying cryptic rearrangements. In
      order to determine the frequency of these rearrangements in AML cases with +8,
      del(9q) or +22 we have performed an analysis of 63 such patients in whom there
      was no evidence of a t(15;17), t(8;21) or inv(16) by cytogenetics. No disease
      related fusion transcripts were identified, indicating that the secondary changes
      are rarely markers for cryptic rearrangements.

PMID- 9609532
TI  - Microsatellite instability in adult T-cell leukaemia.
AB  - Microsatellite instability (MSI) is thought to represent a defect of the DNA
      mismatch repair system which has been implicated in the tumourigenesis of several
      human malignancies. We investigated MSI in acute/ lymphomatous adult T-cell
      leukaemia (ATL: n=22) using 54 highly polymorphic dinucleotide short-tandem
      repeat sequences. The corresponding control DNA from each individual was obtained
      from the peripheral blood in either chronic phase (n=5) or when complete
      remission was achieved (n=17). 10/22 (41%) patients had MSI, six of whom showed
      MSI in multiple loci; four loci had MSI in multiple samples. The incidence of MSI
      in ATL was found to be higher than in other haematological malignancies,
      indicating MSI as a feature of ATL, which may be involved in the progression of
      the disease.

PMID- 9609533
TI  - Primary central nervous system lymphoma in a child with acute B-cell
      lymphoblastic leukaemia: consecutive Epstein-Barr virus-related malignancies.
AB  - Primary central nervous system lymphoma (PCNSL), observed among immunocompromised
      AIDS patients, has not been reported during chemotherapy for acute lymphoblastic
      leukaemia (ALL). We report a case of PCNSL occurring in a child receiving
      intensive multiagent chemotherapy for B-cell ALL. In situ hybridization studies
      demonstrated Epstein-Barr virus genome in both tumours, suggesting a possible
      link between the two diseases. The clinical response of the PCNSL to conservative
      therapy highlights the importance of accurately diagnosing such EBV-related
      disorders, especially in patients where immune compromise can be reversed.

PMID- 9609534
TI  - DNA extraction from archival Giemsa-stained bone-marrow slides: comparison of six
      rapid methods.
AB  - The ability of six rapid DNA extraction procedures to provide DNA for the
      polymerase chain reaction from archival Giemsa-stained bone marrow slides was
      tested on 120 samples. Boiling in distilled water, freeze-thaw method, boiling in
      10% Chelex-100 resin solution, proteinase K/Tween 20/NP-40 method coupled with
      simplified phenol/ chloroform/isoamyl alcohol protocol or salting-out procedure
      using saturated NaCl and modification of commercial QIAamp procedure (Qiagen.
      Chatsworth, Calif.) gave DNA extraction efficiencies of 50%, 70%, 85%, 95%, 100%
      and 100%, respectively. Our results demonstrate that rough DNA extraction methods
      have decreased efficiencies compared to complete DNA extraction protocols and
      that the latter are required to ensure highly reproducible results from archival
      Giemsa-stained bone marrow slides.

PMID- 9609535
TI  - Expansion of dendritic cells derived from human CD34+ cells in static and
      continuous perfusion cultures.
AB  - We examined the effects of different cytokine combinations and culture conditions
      on the expansion and modulation of cell surface antigens of CD34+ derived
      dendritic cells (DCs), the most efficient antigen-presenting cells capable of
      stimulating resting T cells in the primary immune response. Cells with a
      dendritic morphology and expressing HLA-DR, CD1a, S100 and CD83 were maximally
      expanded under serum-free conditions with the addition of SCF, GM-CSF, TNF-alpha,
      TGF-beta and Flt-3 ligand (fold increase of CD1a+ cells = 102 +/- 32 after 2
      weeks of culture). CD34+ cells were also grown under continuous flow conditions
      in an artificial capillary system: after 14d of culture, the expansion in the
      total cell number was lower than that of the static cultures (3.3 +/- 2 v 18.9 +/
      4) but the percentage of CD1a+/CD83+/ CD80+ cells was considerably higher,
      whereas the CD14+ cells were significantly reduced (8.9 +/- 2 v 26 +/- 13). In
      continuous perfusion cultures, low levels of DC precursors and of LTC-IC were
      still present up to day 14. The DCs generated under flow conditions stimulated
      the mixed leucocyte reaction (MLR) more than the cells grown in static cultures.
      By electron microscopy, cells grown in the continuous flow system showed an
      increased number of large cells with numerous dendritic processes and abundant
      multilamellar complexes. The cells expanded under these conditions were sorted on
      the basis of their light-scatter properties into two fractions: one containing a
      predominance of CD1a+/S100+/ CD8 3+/CD80+/CD14- 'large cells' with great internal
      complexity (mature DCs); the second including 'small cells' either CD33+/CD14+,
      CD33+/CD15+ or CD33+/CD13-/CD14. The DCs generated and selected with this method
      are therefore particularly well suited for immunotherapeutic protocols.

PMID- 9609536
TI  - Rheological properties and function of blood cells in stored bank blood and
      salvaged blood.
AB  - The technique involving filtration of diluted blood enables the separate analysis
      of the flow properties of different cell subpopulations. This study was designed
      to assess the changes occurring in the flow properties and function of blood
      cells in stored bank blood and salvaged blood compared to patient blood in a
      given clinical situation. We measured hydrogen peroxide production by neutrophils
      and the filterability, through 5 microm Nucleopore filters, of isolated red blood
      cells and of diluted blood. Samples were obtained from patients undergoing aortic
      surgery and blood intended for transfusion: either salvaged during surgery or
      stored bank blood. Both salvaged and bank blood were much less filterable than
      patient blood, with reduced deformability of both red and white blood cells.
      However, salvaged blood contained highly activated neutrophils with a prolonged
      transit time of the 'fast-flowing' cells in the analysis compared to bank blood.
      Bank blood contained significantly more particles which acted as pore-blockers.
      Cells in bank and salvaged blood therefore have markedly abnormal flow and
      biochemical properties compared to patient blood.

PMID- 9609537
TI  - The effect of HFE mutations on serum ferritin and transferrin saturation in the
      Jersey population.
AB  - High frequencies of the haemochromatosis-related HFE C282Y mutation have been
      reported in North European populations, in which a high proportion of patients
      with the disease are homozygotes. However, the degree of penetrance of this
      genotype is unknown. We determined the HFE C282Y and H63D genotypes of 411
      consenting volunteer blood donors on Jersey, and the serum ferritin and
      transferrin saturation levels of 204 of these volunteers. The C282Y allele
      frequency was found to be 8.3% in 822 chromosomes, indicating a homozygote
      frequency of 1/145. Consistent with this, four C282Y homozygotes were detected in
      411 volunteers. As there are only 18 patients presently receiving treatment for
      haemochromatosis on Jersey, out of a total population of about 85000, there is a
      large discrepancy between the number of haemochromatosis patients and the number
      of C282Y homozygotes in this population. In a preliminary study of 204 consenting
      volunteers we found a correlation between transferrin saturation and HFE H63D/
      C282Y genotype (P=0.017) and between serum ferritin and genotype (P = 0.056). We
      also observed elevated values of transferrin saturation in the two C282Y
      homozygotes assayed. These results suggest that a large proportion of the many
      undetected C282Y homozygotes on Jersey and in similar populations could be in the
      preclinical stages of haemochromatosis, and warrant investigation. However, there
      may be a wide variation in the expression of the condition, and a more extensive
      study of the level of disease penetrance encompassing a large number of hitherto
      undetected C282Y homozygotes is therefore imperative.

PMID- 9609538
TI  - Guidelines on oral anticoagulation: third edition.

PMID- 9609539
TI  - Reticulated platelets in primary and reactive thrombocytosis.

PMID- 9609540
TI  - Epidemiology of monoclonal gammopathy in Cote d'Or, France.

PMID- 9609541
TI  - Monitoring oral anticoagulant therapy in patients with lupus anticoagulants.

PMID- 9609542
TI  - Positron emission scanning with 18-FDG in the diagnosis of deep fungal
      infections.

PMID- 9609543
TI  - Non-transferrin bound iron induced by myeloablative therapy.

PMID- 9609544
TI  - Lineage involvement and prognosis in Ph chromosome positive acute lymphoblastic
      leukaemia.

PMID- 9609545
TI  - Effect of early treatment of prostate cancer with the 5alpha-reductase inhibitor
      turosteride in Dunning R3327 prostatic carcinoma in rats.
AB  - BACKGROUND: Turosteride, a selective 5alpha-reductase inhibitor, was reported to
      be effective in inhibiting the growth of established tumors in the Dunning R3327
      rat prostatic carcinoma model. We evaluated the preventive effect of turosteride
      when administered during the latency period in this prostatic tumor model.
      METHODS: Turosteride was given orally, 6 days a week for 10-15 weeks, starting at
      different times: 1) 5 weeks after tumor implantation, when tumors were not yet
      palpable, or 2) 1 day after tumor implantation. In each experiment, one group of
      animals was castrated on the first treatment day. RESULTS: When treatment started
      5 weeks after tumor implantation, neither turosteride (at 50 and 200 mg/kg/day)
      nor castration reduced tumor incidence (91-100%). Tumor growth was reduced in
      groups treated with the highest dose of turosteride and in castrated rats. When
      treatment started 1 day after tumor implantation, castration resulted in a 62%
      tumor incidence compared to 100% in controls, while turosteride at 200 mg/kg/day
      was not effective in reducing tumor incidence. However, as in the previous
      experiment, the compound was highly effective in reducing tumor growth.
      CONCLUSIONS: The antitumor activity profile of turosteride seems not to be
      related to the timing of treatment. Given either 5 weeks or 1 day after tumor
      implantation, the compound did not reduce tumor take, while it maintained
      effective tumor growth-inhibiting activity in both cases.

PMID- 9609546
TI  - Total and regional bone mass and biochemical markers of bone remodeling in
      metastatic prostate cancer.
AB  - BACKGROUND: The osteolytic activity of metastases of prostate cancer was
      evaluated in relation to total body bone mineral content (TBBMC) and regional
      bone mineral content (RBMC). METHODS: Bone mass was determined by dual-energy X
      ray absorptiometry (DXA). Tartrate-resistant acid phosphatase (TRAP) was measured
      as a biochemical marker of bone resorption. RESULTS: In 32 patients (mean age
      72+/-4 years) compared with 32 controls (mean age 73+/-5 years), there were
      significant differences in TRAP (P < 0.0001), TBBMC (P < 0.0001), and RBMC in the
      pelvis (P < 0.0001), legs (P=0.0001), and trunk (P<0.05), but not in the arms and
      head (P=ns). In the overall group of subjects, the correlation between TBBMC and
      TRAP was r=-0.68, P < 0.0001. The correlations remained significant in the
      patient and control groups separately. CONCLUSIONS: The loss of bone mass
      observed in patients with metastatic prostate cancer was caused mainly by the
      predominance of bone resorption in the osteoblastic metastases.

PMID- 9609547
TI  - Synthetic matrix metalloproteinase inhibitor, BB-94, inhibits the invasion of
      neoplastic human prostate cells in a mouse model.
AB  - BACKGROUND: It has been suggested that increased metalloproteinase activity is a
      critical event in neoplastic progression leading to the initiation of local
      invasion and ultimately to the dissemination of neoplastic cells. This has led to
      an interest in testing the ability of metalloproteinase inhibitors to prevent the
      progression of carcinoma in situ into invasive and, therefore, more malignant
      tumors. One such agent is the synthetic matrix metalloproteinase inhibitor, BB
      94. METHODS: The effect of BB-94 on the intrinsic invasive potential of
      matrilysin-transfected Du-145 cells was evaluated by an in vitro invasion assay.
      In addition a diaphragm invasion model, which provides an easily oriented
      structure in which the earliest penetration of the basal lamina can be observed,
      was used to investigate the effect of BB-94 on the invasion and growth of tumors
      formed by these cells when injected into S.C.I.D. mice. RESULTS: The synthetic
      matrix metalloproteinase inhibitor, BB-94, was shown to effectively inhibit the
      invasion of matrigel and murine diaphragm. CONCLUSIONS: Metalloproteinase
      inhibitors, such as BB-94, that are able to limit tumor growth, and local
      invasion, may decrease the invasion of invasive carcinomas.

PMID- 9609548
TI  - Interleukin-6 and epidermal growth factor promote anchorage-independent growth of
      immortalized human prostatic epithelial cells treated with N-methyl-N
      nitrosourea.
AB  - BACKGROUND: Epidermal growth factor (EGF) and interleukin (IL)-6 are implicated
      in the growth of benign and malignant prostatic epithelial cells. We investigated
      the role of EGF and IL-6 during the process of prostate carcinogenesis. METHODS:
      Using growth in soft agar as an index of transformation, we examined the effect
      of EGF and IL-6 on the enhancement of N-methyl-N-nitrosourea (MNU)-initiated
      transformation of immortalized, nontumorigenic prostatic epithelial cell lines
      (PWR-1E and RWPE-1) developed in our laboratory. The effect of EGF and IL-6 on
      the growth of MNU-induced transformants isolated from soft agar was assessed both
      in monolayer culture and in a soft agar. RESULTS: After a 1 hr exposure to N
      methyl-N-nitrosourea (50 microg/ml), cells (5 x 10(4)) were grown in soft agar in
      the presence of EGF (5 ng/ml) or IL-6 (10 or 100 ng/ml). Addition of EGF or IL-6
      significantly increased colony formation in soft agar of both immortalized
      prostatic epithelial cell lines initiated with MNU (P < 0.001-0.05). Only a very
      small number of colonies was observed with the parental cell lines PWR-1E and
      RWPE-1 not exposed to MNU, and their numbers increased by the addition of EGF or
      IL-6. All of the transformants, derived by exposure to MNU and isolated from soft
      agar, exhibited a higher cell growth potential in monolayer cultures than did
      their parental cell lines. Furthermore, as compared to the parental cell lines,
      growth response of MNU-transformants to 5alpha-dihydrotestosterone (5alpha-DHT),
      EGF, or IL-6 in monolayer culture was better in 5 of 8, 6 of 8, and 7 of 8 cell
      lines, respectively. All of the MNU-transformants exhibited a far higher colony
      forming efficiency in soft agar than did the parental cell lines. However, the
      degree of responsiveness to EGF or IL-6 in soft agar varied among the MNU
      transformants. CONCLUSIONS: The results of the present study suggest that IL-6
      and EGF may enhance prostate carcinogenesis in vitro by preferentially
      stimulating the growth of transformed cells.

PMID- 9609549
TI  - Group II phospholipase A2 in human male reproductive organs and genital tumors.
AB  - BACKGROUND: Group II phospholipase A2 (PLA2) is a lipolytic enzyme suggested to
      play a role in inflammation and antibacterial defence. In seminal fluid, the
      concentration of PLA2 is exceedingly high under normal circumstances (about 1,000
      times the concentration in blood plasma of healthy humans). To elucidate the
      origin of the enzyme present in seminal plasma, we investigated the expression of
      group II PLA2 in male reproductive organs both at protein and mRNA levels. In
      addition, the presence of the enzyme was studied in common male genital tumors.
      METHODS: The methods used were immunocytochemistry, in situ hybridization, and
      Northern blotting. RESULTS: Northern blotting gave positive results for group II
      PLA2 mRNA in normal prostate, whereas other normal genital tissues gave negative
      results. Immunohistochemistry and in situ hybridization of group II PLA2 gave
      identical results. The enzyme was produced exclusively by the secretory
      epithelial cells of the prostatic gland. Surprisingly, expression was restricted
      to the posterior lobe and paraurethral glands of the prostate. Cells of prostatic
      adenocarcinoma expressed group II PLA2, whereas cells of other male genital
      tumors contained neither the enzyme protein nor the mRNA of group II PLA2. In
      some cases prostatic cancer cell seemed to express group II PLA2 at a higher rate
      than normal prostatic gland cells. CONCLUSIONS: The high content of group II PLA2
      in seminal plasma is due to the local production and secretion of the enzyme by
      the epithelial cells of the prostatic glands. Group II PLA2 is expressed focally,
      suggesting that specialized prostatic glands secrete this enzyme. All prostatic
      adenocarcinomas tested expressed group II PLA2 in variable amounts.

PMID- 9609550
TI  - Insulin-like growth factor binding protein 5 is associated with involution of the
      ventral prostate in castrated and finasteride-treated rats.
AB  - BACKGROUND: Insulin-like growth factor binding protein (IGFBP)-5 has been
      proposed as a signal for apoptosis in the ovary. To determine the relationship
      between IGFBP-5 and apoptosis during regression of the androgen-deprived
      prostate, rats were castrated or treated with the 5alpha-reductase inhibitor
      finasteride for 4, 9, 14, 21, and 28 days. METHODS: Ventral prostate tissue was
      immunostained for IGFBP-5, and apoptotic cells were identified by in situ end
      labeling of fragmented DNA (TUNEL). To compare the distribution of IGFBP-5 with
      the distribution of apoptotic cells, mirror-image serial sections of prostate
      tissues from normal and day 4 finasteride-treated rats were examined. RESULTS: In
      normal rats, 4+/-1% of prostate epithelial cells stained positively for IGFBP-5,
      and 0.1+/-0.03% demonstrated DNA fragmentation. IGFBP-5 staining peaked at day 9
      with 93 +/-2% and 64+/-13% of epithelial cells staining positively in castrated
      and finasteride-treated rats, respectively. In contrast, DNA fragmentation peaked
      at day 4 in tissues from both castrated and finasteride-treated rats with 7+/-1%
      and 0.7+/-0.3% of epithelial cells, respectively, staining. In the serial
      sections, TUNEL and IGFBP-5 staining were not usually expressed in the same
      cells. CONCLUSIONS: Prostatic involution involves both programmed cell death and
      inhibition of cell growth. Because of the distribution of staining and the
      delayed expression of IGFBP-5 relative to initiation of apoptosis, we postulate
      that IGFBP-5 functions as an inhibitor of cell proliferation rather than as a
      signal for apoptosis.

PMID- 9609551
TI  - Induction of early and bioeffective antibody response in rodents with the
      luteinizing hormone-releasing hormone vaccine given as a single dose in
      biodegradable microspheres along with alum.
AB  - BACKGROUND: Previous studies in animals and phase I/phase II clinical trials in
      humans have shown the suppressive effect of immunization with the luteinizing
      hormone-releasing hormone (LHRH) vaccine on prostatic hypertrophy and
      hyperplasia. A drawback of this vaccine was a delay of about 8 weeks in buildup
      of antibody titers to efficacy level and the requirement of three injections of
      the vaccine given at monthly interval for full primary immunization. METHODS:
      LHRH vaccine was encapsulated in poly-lactic-co-glycolic acid (PLGA) 50:50
      copolymer microspheres of reproducible physicochemical characteristics.
      Immunogenicity studies were carried out in rodents and prostate weights were
      determined at various antibody titers. RESULTS: The vaccine entrapped in
      biodegradable microspheres generated high antibody response in rats, persisting
      for 5-7 months following a single immunization. One hundred micrograms was the
      optimum dose, and the intramuscular route was more immunogenic than the
      subcutaneous. It was further observed that coadministration of 75% of the vaccine
      entrapped in microspheres with 25% adsorbed on alum generated higher antibody
      response in rodents, exceeding the bioeffective threshold as early as day 15
      postimmunization. CONCLUSIONS: Coadministration of the LHRH vaccine in
      biodegradable PLGA microspheres with a quarter of the dose adsorbed on alum
      generates high antibody titers within 15 days, which are effective in causing
      atrophy of the prostate.

PMID- 9609552
TI  - Novel role of zinc in the regulation of prostate citrate metabolism and its
      implications in prostate cancer.
AB  - The prostate gland of humans and many other animals has the major function of
      accumulating and secreting extraordinarily high levels of citrate. This
      specialized metabolic process of "net citrate production" is the result of unique
      metabolic capabilities of the secretory epithelial cells. Most importantly, in
      prostate cancer (Pca) the capability for net citrate production is lost. In
      addition to citrate, the normal and BPH (benign prostatic hyperplasia) prostate
      also accumulates the highest levels of zinc in the body. As with citrate, in Pca
      the ability for high zinc accumulation is diminished. These and other
      correlations between zinc and citrate in the prostate have been indicative of an
      important role of zinc in the regulation of citrate metabolism in normal and
      malignant prostate epithelial cells. The link between zinc and citrate metabolism
      has now been established. The intramitochondrial accumulation of high zinc levels
      inhibits mitochondrial (m-) aconitase activity, which inhibits citrate oxidation.
      This essentially truncates the Krebs cycle and markedly decreases the cellular
      energy (ATP) production normally coupled to citrate oxidation. It is also clear
      that zinc accumulation in citrate-producing prostate epithelial cells is
      regulated by testosterone and by prolactin. These relationships form the basis
      for a new concept of the role of zinc and citrate-related energy metabolism in
      prostate malignancy. The inability of malignant prostate cells to accumulate high
      zinc levels results in increased citrate oxidation and the coupled ATP production
      essential for the progression of malignancy. The concept offers new approaches to
      the treatment of Pca.

PMID- 9609553
TI  - Evaluating the outcome of surgery for pelvic organ prolapse.

PMID- 9609554
TI  - Single and repetitive maternal glucocorticoid exposures reduce fetal growth in
      sheep.
AB  - OBJECTIVE: We evaluated the effects of single or three repeated doses of maternal
      betamethasone on fetal growth at preterm and term delivery in sheep. STUDY
      DESIGN: Pregnant ewes were randomly assigned to receive one dose of 0.5 mg/kg
      betamethasone at 104 days' gestational age; three doses of betamethasone at 104,
      111, and 118 days' gestational age; or saline for controls. Lambs were delivered
      at 125 days' (preterm) or at 145 days' (term) gestational age for assessments of
      fetal growth. RESULTS: The single betamethasone exposure at 104 days' gestational
      age caused symmetric growth retardation of 11% at 125 days' gestational age and
      14% at term. The three-dose exposures decreased body weights by 25% in preterm
      lambs and by 19% at term. Organ protein and deoxyribonucleic acid per kilogram of
      body weight were selectively decreased in preterm lambs. At term the decreases in
      organ weight, protein, and deoxyribonucleic acid were proportionate to the
      decreased birth weight. CONCLUSION: One or three doses of maternal
      glucocorticoids begun at an early gestational age caused symmetric growth
      retardation in lambs delivered prematurely, and the decreased fetal size
      persisted to term.

PMID- 9609555
TI  - Urinary compound W in pregnant women is a potential marker for fetal thyroid
      function.
AB  - OBJECTIVE: Previously we reported 3,3'-diiodothyronine sulfate-like material
      (compound W) in maternal serum, and studies suggest that compound W is derived
      from thyroid hormones of fetal origin. In this study we characterized gestational
      changes of urinary compound W concentrations to correlate with changes in serum
      concentrations. STUDY DESIGN: Urinary samples were collected from 94 women at
      various gestational ages ranging from 3 to 40 weeks. Urinary compound W was first
      identified biochemically. The concentrations of compound W (adjusted for
      creatinine levels) were assessed by a 3,3'-diiodothyronine sulfate
      radioimmunoassay in ethanol extracts of urine samples. RESULTS: Compound W
      increased to 88 +/- 1.4 pmol (of 3,3'-diiodothyronine sulfate equivalent)/mmol
      creatinine in urinary samples obtained from 26 women in the first trimester of
      pregnancy compared with 40 +/- 6.9 pmol/mmol creatinine in 10 nonpregnant women.
      Excretion of compound W increased further during the second and third trimesters:
      171 +/- 17 (n = 18) and 434 +/- 26 (n = 50) respectively. In contrast, urinary
      3,3',5-triiodothyronine sulfate concentrations measured by radioimmunoassay were
      similar during pregnancy to values in nonpregnant women. CONCLUSIONS: Urinary
      compound W concentrations increase with the progression of normal pregnancy and
      correlate with the increase in serum levels. Random spot urine compound W
      concentrations, adjusted for creatinine levels, may be used in place of serum
      levels in conditions in which obtaining serum samples may be technically
      difficult, especially during population screening.

PMID- 9609556
TI  - Effects of ouabain on the isolated human uteroplacental vasculature.
AB  - OBJECTIVE: We sought to describe the effects of ouabain on the human
      uteroplacental vasculature. STUDY DESIGN: Stem villous vessels and
      intramyometrial arteries isolated from placental and myometrial biopsy specimens
      at term were mounted in organ baths. Moreover, isolated human placental
      cotyledons were perfused. RESULTS: Contractions induced by the thromboxane A2
      analog U46619 were unaffected by pretreatment with ouabain 10(-10) to 10(-6)
      mol/L. In fetal vessels nitric oxide (10(-8) to 3 x 10(-5) mol/L) induced
      relaxation of vascular tonus induced by U46619 and potassium. This relaxation was
      inhibited by pretreatment with ouabain 10(-7) to 10(-6) mol/L. These associations
      were unaffected by removal of the endothelium. In maternal arteries ouabain (10(
      6) mol/L) failed to significantly affect nitric oxide-induced relaxation. Ouabain
      (10(-9) mol/L) significantly affected pressure-flow relationships in perfused
      cotyledons. CONCLUSIONS: Ouabain impairs nitric oxide-induced relaxation of human
      stem villous arteries and veins, which may explain the changes induced by
      therapeutically relevant concentrations of the drug on pressure-flow
      relationships in the perfused cotyledon. Thus treatment with cardiac glycosides
      in pregnancy may impair uteroplacental blood flow.

PMID- 9609557
TI  - Concomitant use of glucocorticoids: a comparison of two metaanalyses on
      antibiotic treatment in preterm premature rupture of membranes.
AB  - OBJECTIVE: This study was performed to investigate whether the demonstrated
      beneficial effects of antibiotics on maternal and neonatal morbidity are altered
      when glucocorticoids are part of the treatment of preterm premature rupture of
      membranes. STUDY DESIGN: We performed a metaanalysis of five published,
      randomized trials of antibiotic treatment in preterm premature rupture of
      membranes in which glucocorticoids were used as additional treatments and
      compared the results with those of a previously published metaanalysis of
      antibiotic treatment in preterm premature rupture of membranes, which excluded
      studies with concomitant glucocorticoids. Primary outcomes included
      chorioamnionitis, postpartum endometritis, neonatal sepsis, respiratory distress
      syndrome, intraventricular hemorrhage, necrotizing enterocolitis, and neonatal
      mortality. A logistic regression analysis was performed to test whether
      glucocorticoids significantly influenced the effect of antibiotic treatment.
      RESULTS: Among the 509 patients from five trials on antibiotic and glucocorticoid
      treatment published between 1986 and 1993 antibiotic therapy did not show any
      significant effect on any of the outcomes analyzed. In contrast, antibiotic
      therapy without concomitant use of glucocorticoids significantly reduced the odds
      of chorioamnionitis, postpartum endometritis, neonatal sepsis, and
      intraventricular hemorrhage by 62%, 50%, 68%, and 50%, respectively. The logistic
      regression analysis showed that glucocorticoids significantly diminished the
      effect of antibiotic treatment on chorioamnionitis and neonatal sepsis.
      CONCLUSION: Glucocorticoids appear to diminish the beneficial effects of
      antibiotics in the treatment of preterm premature rupture of membranes. A careful
      selection of patients who are likely to benefit from both therapies is therefore
      recommended.

PMID- 9609558
TI  - The impact of fetal compromise on outcome at the border of viability.
AB  - OBJECTIVE: Our goal was to evaluate the impact of fetal compromise on the outcome
      of borderline viable babies. STUDY DESIGN: All 142 babies born in our hospital
      from 1990 to 1995 with a gestational age of 23 to 25 weeks were included. Fetal
      compromise was considered present if one of the following was documented: a major
      anomaly, congenital sepsis, chronic intrauterine infection, intrauterine drug
      exposure, congenital anemia, severe growth restriction, fetal acidosis, or
      cardiorespiratory and neurologic depression in the delivery room. RESULTS: The 43
      babies who had at least one cause of fetal compromise had a lower birth weight (p
      < 0.001), but there were no other differences in demographics or complications of
      prematurity. The survival rate was significantly better for babies free of fetal
      compromise (75% vs 33%, p < 0.001), particularly for babies born at 23 weeks of
      gestation (75% vs 6%, p < 0.001). For surviving babies free of fetal compromise,
      the outcome at 23 weeks was comparable to that at 24 to 25 weeks for major causes
      of long-term neurologic morbidity. CONCLUSIONS: Like advancing gestational age
      and increasing birth weight, the absence of fetal compromise has a major
      beneficial impact on the outcome of borderline viable babies that might be
      important when decisions are made about the appropriate level of support.

PMID- 9609559
TI  - Ultrasonographic examination of intrauterine growth for multiple fetal dimensions
      in a Chinese population. Central-South China Fetal Growth Study Group.
AB  - OBJECTIVE: We sought to construct an ultrasonography-based growth curve in a
      Chinese population. STUDY DESIGN: Routine ultrasonographic examination was
      performed in 5496 normal pregnancies (>95% first births) in five obstetric
      ultrasonography laboratories in Central-South China from January 1, 1992, to
      December 31, 1993. RESULTS: All the fetal growth measures increased with
      gestational age, whereas the ratios either decreased or remained constant across
      gestation. Biparietal diameter and cerebral hemispheric width were higher at
      early gestational ages, whereas femur length, thoracic circumference, and
      abdominal circumference were lower at later gestational ages in our study than in
      previous studies. The ratio of lateral ventricular width/cerebral hemispheric
      width was lower at an early gestational age but higher in later gestational ages
      in our study. CONCLUSIONS: A different standard of ultrasonography-based fetal
      growth is needed for different populations. The ultrasonography-based growth
      curve constructed in this large Chinese population provides an additional tool
      for the evaluation of fetal growth and development.

PMID- 9609560
TI  - Elective delivery of infants with macrosomia in diabetic women: reduced shoulder
      dystocia versus increased cesarean deliveries.
AB  - OBJECTIVE: We sought to test the hypothesis that elective delivery of infants
      diagnosed with macrosomia by ultrasonographic studies in diabetic women will
      significantly reduce the rate of shoulder dystocia without significantly
      increasing cesarean section rate. STUDY DESIGN: In a prospective study diabetic
      women with ultrasonographic estimated fetal weight > or = 4250 gm underwent
      elective cesarean section; women with estimated fetal weight > or = 90th
      percentile but < 4250 gm underwent induction of labor. Maternal and neonatal
      outcomes were analyzed and compared for the periods before and after initiation
      of the protocol. RESULTS: A total of 2604 diabetic patients were included in this
      study. The rate of shoulder dystocia was significantly lower after instituting
      the protocol (2.4% vs 1.1%, odds ratio 2.2). The cesarean section rate increased
      significantly between the two periods (21.7% vs 25.1%, p < 0.04). Ultrasonography
      correctly identified the presence or absence of macrosomia in 87% of patients.
      Only 10.6% of diabetic patients at term required intervention under the protocol
      (6.8% labor induction, 3.8% elective cesarean section). The rate of shoulder
      dystocia was 7.4% in macrosomic infants delivered vaginally. CONCLUSION: An
      ultrasonographically estimated weight threshold as an indication for elective
      delivery in diabetic women reduces the rate of shoulder dystocia without a
      clinically meaningful increase in cesarean section rate. This practice, in
      conjunction with an intensified management approach to diabetes, improves the
      outcome of these high-risk women and their infants.

PMID- 9609561
TI  - A positive umbilical venous-arterial difference of leptin level and its rapid
      decline after birth.
AB  - OBJECTIVE: We investigated the site of leptin production in the fetoplacental
      circulation. STUDY DESIGN: We simultaneously determined plasma leptin levels in
      cord vessels and maternal peripheral veins of 38 healthy pregnant women. We also
      compared plasma leptin levels in 20 neonates at birth and on the fifth day after
      birth. RESULTS: Leptin levels in cord vessels were significantly (p < 0.001)
      lower than those in maternal veins (mean 29.5 ng/ml). Leptin levels in umbilical
      arteries (mean 9.8 ng/ml) were significantly (p < 0.01) lower than those in
      umbilical veins (mean 12.9 ng/ml). Leptin levels in neonatal veins on the fifth
      day (mean 3.0 ng/ml) were markedly (p < 0.001) lower than those in umbilical
      arteries of the same neonates (mean 10.9 ng/ml). CONCLUSION: The higher leptin
      levels in umbilical veins than in umbilical arteries and the marked decrease
      during the neonatal period suggest that the placenta is one of the major sources
      of leptin in the fetal circulation.

PMID- 9609562
TI  - Gestational age changes in circulating CD34+ hematopoietic stem/progenitor cells
      in fetal cord blood.
AB  - OBJECTIVE: We sought to evaluate the frequency of CD34+ hematopoietic
      progenitor/stem cells across gestation and the proliferative response of early
      versus late gestational age fetal blood to growth factor stimulation. STUDY
      DESIGN: Fetal blood samples were obtained at 17 to 41 weeks' gestational age. The
      mononuclear cell population was separated by red blood cell lysis. The frequency
      of CD34+ cells within the lymphocyte-monocyte light scatter gate and the
      expression of CD34 by colony-forming cells of different types were determined by
      fluorescence-activated cell sorting. The growth response of colony-forming cells
      to varying concentrations of defined growth factors (interleukin-3, interleukin
      6, granulocyte-macrophage colony-stimulating factor, stem cell factor, and
      erythropoietin) was determined, as well as the frequency of burst-forming units
      erythroid, colony-forming units granulocyte-macrophage, and total colony-forming
      cells. Samples from 17 to 24 weeks' gestation (early) were compared with those of
      39 to 41 weeks' gestation (late). RESULTS: The frequency of CD34+ cells in early
      fetal blood (17 to 24 weeks' gestation) was 4.9-fold higher (6.4% vs 1.3%, p <
      0.002) than term gestation (37 to 41 weeks' gestation) and declined linearly with
      gestational age (p < 0.0001). When gestational ages were grouped into 4-week
      blocks (17 to 20, 21 to 24, 25 to 28, 29 to 32, 33 to 36, and >37 weeks),
      statistically significant changes in the frequency of CD34+ cells did not occur
      until after 28 weeks' gestation. By cell sorting, >99% of all colony-forming
      cells were contained within the CD34+ population at all gestational ages tested.
      Compared with term, the frequency of colony-forming cells was significantly
      greater in early fetal blood (burst-forming units erythroid [18.1-fold, p <
      0.0001], colony-forming units granulocyte-macrophage [2.9-fold, p <0.001], and
      total colony-forming cells [9.4-fold, p < 0.0001]). However, when the frequency
      of colony-forming cells was corrected for the frequency of CD34+ cells, only the
      number of burst-forming units erythroid remained significantly greater in early
      fetal blood. The relative size of the colonies formed by individual progenitors
      from early fetal blood was greater than those from term samples. CONCLUSIONS:
      From 17 to 41 weeks' gestation the frequency of CD34+ cells in fetal blood, which
      includes hematopoietic progenitors and stem cells, decreases. This decline occurs
      during the transition from hepatic to bone marrow hematopoiesis. Early fetal
      blood, with a higher circulating frequency of progenitor/stem cells and
      proliferative capacity, may be a preferable target for gene therapy.

PMID- 9609563
TI  - Fetal membrane closure techniques after hysteroamniotomy in the midgestational
      rabbit model.
AB  - OBJECTIVE: We studied closure techniques for amniotic access in midgestational
      rabbits. STUDY DESIGN: Twenty-eight rabbits with a total of 313 amniotic sacs
      were used for this study. In each animal a 1 cm hysteroamniotomy was made in two
      amniotic sacs at 22 days' gestation (term = 32). For 12 amniotic sacs (group 1)
      only the myometrium was closed by microsurgical suturing. In group 2 (n = 12),
      sutures included myometrium and membranes. In group 3 (n = 8), a collagen plug
      was placed, and in group 4 (n = 12) fibrin glue was used. Twelve sacs were left
      unclosed (positive controls) and the unmanipulated 257 sacs were negative
      controls. Eight days later (gestational age 30 days) amniotic sacs were evaluated
      for the presence of amniotic fluid, membrane integrity, and fetal weight and
      survival. Statistics were done with two-tailed Fisher's exact test and one-way
      analysis of variance. RESULTS: Membrane integrity (p = 0.0036) and amniotic fluid
      (p = 0.047) were best restored after myometrial closure. Fetal weight and
      survival rate were not affected by different closure techniques. CONCLUSION: In
      this model primary closure of the myometrium only yielded best results.

PMID- 9609564
TI  - Blood flow through the ductus venosus in singleton and multifetal pregnancies and
      in fetuses with intrauterine growth retardation.
AB  - OBJECTIVE: It is known from animal experiments that blood flow through the ductus
      venosus changes with fetal strain. Therefore the ratio of umbilical vein to
      ductus venosus flow rate in human intrauterine growth retardation and multifetal
      pregnancies was investigated and compared with that in control subjects. STUDY
      DESIGN: Blood flow rates in the umbilical vein and in the ductus venosus, as well
      as peak velocity, minimum velocity, mean velocity, and pulsatility index (maximum
      velocity envelope curve) in the ductus venosus, were measured in women with
      normal pregnancies (n = 55), intrauterine growth retardation (n = 20), and
      multifetal pregnancies (10 women with 20 fetuses) with color Doppler
      ultrasonography. RESULTS: Average ductus venosus blood flow rates (mean +/- SD),
      normalized for estimated fetal body weight, were 60 +/- 30, 69 +/- 35, and 77 +/-
      28 (ml x min(-1) x kg(-1)) in control subjects, intrauterine growth retardation,
      and multifetal pregnancies, respectively. Umbilical vein blood flow rates
      amounted to 140 +/- 59, 111 +/- 54, and 141 +/- 47 (ml x min(-1) x kg(-1)). Both
      absolute flow rates increased with gestational age, whereas normalized flow rates
      decreased. The percentage of umbilical blood flow passing through the ductus
      venosus in the control group was 43% + 9%. It was significantly increased in both
      intrauterine growth retardation (62% +/- 8%) and in multifetal pregnancies (55%
      +/- 12%). Peak velocity, minimum velocity, mean velocity, and pulsatility index
      in the ductus venosus were not significantly different between groups.
      CONCLUSION: The increased ratio of ductus venosus blood flow to umbilical vein
      blood flow may indicate fetal strain.

PMID- 9609565
TI  - Baroreflex-mediated bradycardia but not tachycardia is blunted peripherally by
      intravenous mu-opioid agonists.
AB  - OBJECTIVE: We sought to test the hypothesis that an intravenous dose of H-Tyr-D
      Arg-Phe-Lys-NH2, a highly mu-receptor selective opioid peptide, suppresses
      baroreflex sensitivity through a peripheral mechanism. STUDY DESIGN: A transient
      change in mean arterial pressure was produced in chronically instrumented
      pregnant ewes by norepinephrine or sodium nitroprusside in the absence or in the
      presence of H-Tyr-D-Arg-Phe-Lys-NH2, a highly mu-selective opioid peptide. In
      some studies naloxone methiodide, a peripheral opioid antagonist, was infused
      starting 60 minutes before the administration of H-Tyr-D-Arg-Phe-Lys-NH2 and
      maintained for a total of 90 minutes. Linear plots were obtained when the changes
      in mean arterial pressure during the pressure rise were plotted against the
      changes in heart rate and the sensitivity of the baroreflex was derived as the
      slope of the linear regression line. RESULTS: We observed (1) lower baroreflex
      sensitivity after H-Tyr-D-Arg-Phe-Lys-NH2 administration with a hypertensive
      stimulus; (2) unchanged baroreflex sensitivity after H-Tyr-D-Arg-Phe-Lys-NH2
      administration with a hypotensive stimulus; and (3) unchanged baroreflex
      sensitivity after H-Tyr-D-Arg-Phe-Lys-NH2 administration with a hypertensive
      stimulus in the presence of naloxone methiodide. CONCLUSION: H-Tyr-D-Arg-Phe-Lys
      NH2 suppresses the hypertensive but not the hypotensive arm of the baroreflex
      through peripheral opioid receptors. These results suggest that mu-opioid
      receptors are present in the vagus nerves and that the activation of these opioid
      receptors inhibits reflex bradycardia in pregnant sheep.

PMID- 9609566
TI  - Triage of abnormal postmenopausal bleeding: a comparison of endometrial biopsy
      and transvaginal sonohysterography versus fractional curettage with hysteroscopy.
AB  - OBJECTIVE: We sought to compare the combined diagnostic reliability of
      sonohysterography and endometrial biopsy with fractional curettage with
      hysteroscopy in the initial evaluation of postmenopausal women with abnormal
      uterine bleeding. STUDY DESIGN: This year-long, prospective, controlled, clinical
      investigation was initiated Sept. 1, 1995. All postmenopausal women with abnormal
      uterine bleeding were offered inclusion, with 104 enrolled. An endometrial biopsy
      was performed at the time of initial evaluation. Routine transvaginal
      ultrasonography was then used to measure the uterus, ovaries, and endometrial
      stripe thickness, followed immediately by sonohysterography to evaluate the
      symmetry of endometrial wall thickness and delineate any intraluminal masses.
      Definitive histopathologic sampling was obtained by fractional curettage with
      hysteroscopy and statistically compared with the diagnoses arrived at by
      endometrial biopsy and sonohysterography. RESULTS: The combination of endometrial
      biopsy and transvaginal sonohysterography positively correlated with the surgical
      findings >95% of the time, with a sensitivity and specificity of 94% and 96%,
      respectively (confidence interval 91% to 99%). No patients with endometrial
      hyperplasia or cancer were misdiagnosed. CONCLUSIONS: Sonohysterography combined
      with endometrial biopsy is a reliable office tool for evaluating postmenopausal
      women with abnormal uterine bleeding. Medical management of those patients
      identified as having no endometrial abnormalities can be considered with
      confidence, while saving the cost and surgical risk of fractional curettage.
      Patients with intraluminal masses should be referred for surgical management in a
      timely fashion.

PMID- 9609567
TI  - Reflex human papillomavirus deoxyribonucleic acid testing in women with abnormal
      Papanicolaou smears.
AB  - OBJECTIVE: The study examined interrelationships between sensitivity and
      specificity of "reflex human papillomavirus deoxyribonucleic acid testing" from
      liquid-based cervical cytologic specimens by means of receiver operator
      characteristics curves. STUDY DESIGN: A cohort study was performed on 265 women
      evaluated by colposcopy because of atypical squamous cells of undetermined
      significance or low-grade squamous intraepithelial lesion found on Papanicolaou
      smear. RESULTS: At a positive threshold of 0.2 pg/ml (1000 copies of human
      papillomavirus per test), human papillomavirus deoxyribonucleic acid testing
      detected 86% of women with cervical intraepithelial neoplasia and 93% of women
      with high-grade cervical intraepithelial neoplasia with a specificity of 30%.
      Decreasing the sensitivity of the human papillomavirus test to 1 pg/ml (5000
      copies of human papillomavirus per test) improved the specificity of a positive
      result to 44% but decreased the clinical sensitivity to 78% for cervical
      intraepithelial neoplasia grade 2 or 3. Relationships between sensitivity and
      specificity were influenced by patient age and referral diagnosis. For example,
      limiting the analysis to only women with a referral for atypical squamous cells
      of undetermined significance found on Papanicolaou smear and a positive human
      papillomavirus test threshold of 0.5 pg/ml produced a sensitivity of 90% for
      cervical intraepithelial neoplasia grade 2 or 3 and a test specificity of 55%.
      CONCLUSION: Human papillomavirus deoxyribonucleic acid testing of residual
      cellular material from liquid cytologic specimens appears to be more appropriate
      for older women (>30 years old) and women with atypical squamous cells of
      undetermined significance, as opposed to low-grade squamous intraepithelial
      lesion, on their Papanicolaou smears.

PMID- 9609568
TI  - Ureteral complications with operative gynecologic laparoscopy.
AB  - OBJECTIVE: The study assessed the incidence, diagnosis, management, and causes of
      ureteral injuries during major laparoscopic operations at our department in a 6
      year period. STUDY DESIGN: The study was a chart review of 790 consecutive major
      laparoscopic procedures in 711 patients (mean age 37.4 +/- 11.6 years, mean
      weight 64.3 +/- 29.1 kg). RESULTS: There were four ureteral complications in
      three patients during or after laparoscopic operations: three of 711 patients
      (0.42%) and four of 790 procedures (0.38%). All three ureteral complications (one
      transection and a total of three ureterovaginal fistulas in two patients)
      occurred during laparoscopically assisted vaginal hysterectomies, for an
      incidence of 4.3%. There were no ureteral injuries in 291 salpingo
      oophorectomies, 414 ovarian cystectomies, and 15 colposuspensions. Both delayed
      ureteral complications occurred in the lower segment of the ureter after
      laparoscopic bipolar coagulation and division of the cardinal ligament.
      CONCLUSION: We conclude that in laparoscopic surgery the ureter is most at risk
      when the cardinal ligament is dissected and divided below the uterine vessels.

PMID- 9609569
TI  - Liposuction-assisted nerve-sparing extended radical hysterectomy: oncologic
      rationale, surgical anatomy, and feasibility study.
AB  - OBJECTIVE: Our purpose was to improve the therapeutic index of radical
      hysterectomy by extending the resection of parametrial tissue without further
      impairing pelvic autonomic nerve functions. STUDY DESIGN: We studied the
      topographic anatomy of the parametrial tissue with high-resolution magnetic
      resonance imaging and by dissection of fresh human cadavers. We then performed a
      clinical feasibility study of the liposuction-assisted nerve-sparing extended
      radical hysterectomy. RESULTS: Magnetic resonance imaging demonstrated that the
      perispinous adipose tissue is retained after type III radical hysterectomy and is
      a frequent site of tumor recurrence. The perispinous adipose tissue contains the
      pelvic plexus, the pelvic splanchnic nerves, small blood vessels, and lymphatic
      tissue. We developed the liposuction-assisted nerve-sparing extended radical
      hysterectomy and applied it to seven consecutive patients with cervical or
      vaginal cancer. No intraoperative or postoperative complications occurred.
      Postoperative magnetic resonance imaging assured us that perispinous adipose
      tissue was cleared in all cases. A metastatic lymph node was found in the
      perispinous adipose tissue removed by liposuction from one patient. Suprapubic
      cystostomies could be removed after a median period of 12 days. CONCLUSION: The
      nerve-sparing removal of perispinous adipose tissue by liposuction is a feasible
      addition to wide en bloc parametrectomy in anatomically defined planes.

PMID- 9609570
TI  - Severity of pelvic inflammatory disease as a predictor of the probability of live
      birth.
AB  - OBJECTIVE: Our aim was to study the association between severity of pelvic
      inflammatory disease at laparoscopy and the probability of achieving a live
      birth, while accounting for subsequent episodes of pelvic inflammatory disease.
      STUDY DESIGN: Beginning in 1960 a cohort of 1288 women in Lund, Sweden, who had
      clinical symptoms of acute pelvic inflammatory disease and who desired pregnancy
      was followed for up to 24 years. All participants underwent laparoscopy and were
      categorized by degree of salpingitis: mild (n = 371), moderate (n = 580), or
      severe (n = 337) pelvic inflammatory disease. Cumulative live birth rates,
      obtained by life-table analysis, and proportional hazards ratios were compared
      among women by severity of pelvic inflammatory disease, while accounting for
      subsequent episodes. RESULTS: The cumulative proportion of women achieving a live
      birth after 12 years was 90% for women with mild, 82% for women with moderate,
      and 57% for women with severe pelvic inflammatory disease. The occurrence of
      subsequent episodes in women with mild pelvic inflammatory disease did not
      diminish their long-term probability of live birth, whereas it significantly
      lowered the probability of live birth in women with severe pelvic inflammatory
      disease. Women with severe disease and subsequent episodes were eight times more
      likely to fail to achieve live birth compared with women with a single pelvic
      inflammatory disease episode with mild disease (relative risk 8.1; 95% confidence
      interval 3.0 to 22.2). CONCLUSIONS: Increasing severity of pelvic inflammatory
      disease correlates with a lower long-term probability of live birth. Subsequent
      episodes have a greater impact on women with severe pelvic inflammatory disease
      at the index episode compared with those with milder disease.

PMID- 9609571
TI  - A longitudinal study of human papillomavirus carriage in human immunodeficiency
      virus-infected and human immunodeficiency virus-uninfected women.
AB  - OBJECTIVE: We sought to determine the relationship of human immunodeficiency
      virus serostatus to carriage of oncogenic human papillomavirus. MATERIAL AND
      METHODS: A total of 268 human immunodeficiency virus-infected and 265 human
      immunodeficiency virus-uninfected women were seen every 6 months, at which time
      they had laboratory tests performed including a CD4 count. Human papillomavirus
      deoxyribonucleic acid was analyzed by polymerase chain reaction. Statistical
      methods included Kaplan-Meier and Cox's proportional hazard models. RESULTS: The
      prevalence at baseline of any human papillomavirus type was 73% and 43% among
      human immunodeficiency virus-seropositive and seronegative women, respectively (p
      < 0.0001) and of oncogenic types was 32.5% and 17.0% (p < 0.001). The prevalence
      of oncogenic human papillomavirus was higher in women with CD4 counts <200 mm3 (p
      < 0.001). The rate of detection of new oncogenic human papillomavirus per 100
      patient years of follow-up in human immunodeficiency virus-seropositive women was
      almost three times higher than among human immunodeficiency virus-seronegative
      women (p < 0.01). The rate of loss of an oncogenic human papillomavirus was
      higher in the human immunodeficiency virus-seronegative women but the difference
      was not significant. The relative risk of a human immunodeficiency virus-infected
      woman who did not initially have a specific type of oncogenic human
      papillomavirus having one detected during follow-up was 6.6 times greater than
      among human immunodeficiency virus-negative women (p < 0.001). CONCLUSIONS: Human
      immunodeficiency virus-seropositive women are more likely to have newly
      detectable oncogenic types of human papillomavirus at follow-up and to show
      persistent carriage of oncogenic types of human papillomavirus types. Among human
      immunodeficiency virus-infected women, those with higher CD4 counts were more
      likely to have a newly detected oncogenic human papillomavirus during follow-up.

PMID- 9609572
TI  - Risk factors for plasma cell endometritis among women with cervical Neisseria
      gonorrhoeae, cervical Chlamydia trachomatis, or bacterial vaginosis.
AB  - OBJECTIVE: We sought to determine potential risk factors for upper genital tract
      inflammation in women with cervical Neisseria gonorrhoeae, Chlamydia trachomatis,
      or bacterial vaginosis. STUDY DESIGN: In a case-controlled study we compared 111
      women with cervical Neisseria gonorrhoeae, Chlamydia trachomatis, or bacterial
      vaginosis (the study group) with 24 women who had negative tests for each of
      these infections (the control group). We evaluated potential risk factors for
      upper genital tract inflammation by use of bivariate and then logistic regression
      analysis. RESULTS: We found plasma cell endometritis in 53 of 111 women in the
      study group and 3 of 24 controls (odds ratio = 6.4, 95% confidence interval 1.7
      to 35.0). On logistic regression, the study group women who were in the
      proliferative phase had increased likelihood of plasma cell endometritis (odds
      ratio = 4.5, 95% confidence interval 1.6 to 12.4). CONCLUSION: The proliferative
      phase of the menstrual cycle seems to be the primary risk factor for ascending
      infection by organisms associated with pelvic inflammatory disease. This may be
      due to a hormonal effect or to the loss of the cervical barrier during
      menstruation.

PMID- 9609573
TI  - Atypical squamous cells of undetermined significance: management patterns at an
      academic medical center.
AB  - OBJECTIVE: Our intent was to compare the management of patients with atypical
      squamous cells of undetermined significance on cytologic screening at an academic
      center to published guidelines. STUDY DESIGN: We reviewed the management of 223
      atypical squamous cells of undetermined significance cervical smears. Patients
      with a history of dysplasia were excluded. The time interval to and nature of
      follow-up testing was determined, and the influence of atypical squamous cells of
      undetermined significance qualifiers and provider specialty analyzed. RESULTS:
      Initial follow-up consisted of repeat cytologic examination alone in 94% of
      cases. Of patients with follow-up, 29% were retested within 2 months and 68%
      within 4 months. No conclusive differences in management were found by qualifier
      type or by provider specialty. Subsequent high-grade dysplasia was found in 2.6%
      of patients. CONCLUSIONS: A discrepancy exists between published guidelines and
      actual management of patients with atypical squamous cells of undetermined
      significance smears at this medical center. Patients often undergo follow-up
      testing at shorter intervals than those suggested despite a low likelihood of
      finding high-grade disease.

PMID- 9609574
TI  - E-cadherin and its messenger ribonucleic acid in periimplantation phase human
      endometrium in normal and clomiphene-treated cycles.
AB  - OBJECTIVE: The purpose of this investigation was to determine whether treatment
      with clomiphene citrate, which is estrogenic and antiestrogenic, affects the
      expression of the cell adhesion molecule E-cadherin in human periimplantation
      phase endometrium. STUDY DESIGN: Five healthy women were studied for two cycles
      each, a control and a treated (clomiphene 50 mg daily, days 5 through 9) cycle. A
      biopsy specimen of endometrial tissue was studied (8 to 10 days post luteinizing
      hormone surge) for immunohistochemical localization, Western analysis of E
      cadherin with use of a highly specific monoclonal antibody to human E-cadherin,
      and determination of messenger ribonucleic acid for E-cadherin by reverse
      transcription-polymerase chain reaction by use of oligonucleotide primers
      specific to E-cadherin and amplifying a 432 bp fragment. RESULTS: Luteal phase
      plasma progesterone levels were significantly higher in clomiphene cycles. E
      cadherin was immunocytochemically present in endometrium of control and treated
      cycles with no apparent difference in staining intensity. Western blots revealed
      the presence of E-cadherin. It was relatively more abundant in clomiphene-treated
      than control cycles but not significantly different. The message for E-cadherin
      gene is expressed in endometrium of control (n = 5) and clomiphene cycles (n =
      4). CONCLUSIONS: E-cadherin and its gene transcripts are expressed in
      periimplantation phase endometrium and are not significantly affected by
      clomiphene treatment.

PMID- 9609575
TI  - When does estrogen replacement therapy improve sleep quality?
AB  - OBJECTIVE: Our purpose was to evaluate the effect of estrogen replacement therapy
      on sleep complaints by postmenopausal women and to assess the predictive factors
      involved. STUDY DESIGN: Sixty-three postmenopausal women entered a 7-month
      prospective, randomized, double-blind, crossover study consisting of two 3-month
      treatments with estrogen and placebo with a 1-month washout period between. Eight
      Visual Analogic Scale statements about different sleep complaints, the Basic
      Nordic Sleep Questionnaire, scoring of climacteric symptoms, The Beck Depression
      Inventory, and serum estradiol and follicle-stimulating hormone level controls
      were the main outcome measures. RESULTS: Estrogen replacement therapy improved
      sleep quality, facilitated falling asleep, and decreased nocturnal restlessness
      and awakenings (p < 0.001). The subjects were less tired in the mornings and in
      the daytime (p < 0.001) when taking estrogen replacement therapy. Estrogen
      induced sleep improvement was associated with alleviation of vasomotor symptoms
      (r range 0.27 to 0.55), alleviation of somatic symptoms (palpitations and
      muscular pain, r range 0.26 to 0.36), and alleviation of mood symptoms (r range
      0.28 to 0.37) on estrogen replacement therapy. The severity of initial insomnia
      predicted only one estrogen-induced sleep improvement effect: the more the
      subjects experienced insomnia, the better the estrogen replacement therapy
      facilitated falling asleep (r = 0.26, p = 0.040). Estrogen-induced sleep
      improvement was also reported by the 15 climacterically asymptomatic subjects. In
      these subjects initial insomnia scores strongly predicted estrogen-induced sleep
      improvement (r range 0.50 to 0.75). CONCLUSIONS: Estrogen replacement therapy
      significantly diminished sleep complaints among postmenopausal women. Alleviation
      of climacteric symptoms was the most important predictive factor for the
      beneficial effect of estrogen replacement therapy on sleep complaints. The use of
      estrogen replacement therapy in women without self-reported climacteric symptoms
      could also be considered because women do not always recognize their climacteric
      symptoms or they ignore them.

PMID- 9609576
TI  - Longitudinal changes in maternal serum leptin concentrations, body composition,
      and resting metabolic rate in pregnancy.
AB  - OBJECTIVE: We sought to evaluate the longitudinal changes in maternal serum
      leptin concentrations, body composition, and resting metabolic rate during
      pregnancy. STUDY DESIGN: Ten women were evaluated before pregnancy, in early
      pregnancy (12 to 14 weeks), and in late pregnancy (34 to 36 weeks). Leptin
      concentrations were measured by radioimmunoassay, body composition with
      hydrodensitometry with adjustment for total body water, and resting metabolic
      rate by use of indirect calorimetry. RESULTS: Using analysis of variance with
      repeated measures from pregravid to late pregnancy, a 66% increase (mean +/- SD)
      was found in leptin concentrations (in nanograms per milliliter) (before
      pregnancy, 25.4 +/- 19.9; in early pregnancy, 37.5 +/- 26.2; and in late
      pregnancy, 38.4 +/- 27.3, p = 0.003); a 9% increase in body fat (in kilograms)
      (before pregnancy, 29.4 +/- 15.7; in early pregnancy, 28.7 +/- 14.0; in late
      pregnancy, 31.4 +/- 14.6; p = 0.04); a 28% increase in oxygen consumption (in
      milliliters of oxygen per minute) (before pregnancy, 221.2 +/- 29.5; in early
      pregnancy, 230.4 +/- 42.9; in late pregnancy, 285.3 +/- 51.9; p < 0.0001); and a
      9% increase in oxygen consumption (milliliters of oxygen per kilogram per minute)
      (before pregnancy, 3.02 +/- 0.43; in early pregnancy, 3.05 +/- 0.30; in late
      pregnancy, 3.31 +/- 0.37, p = 0.002) with advancing gestation. A significant
      positive correlation was present between leptin and body fat before pregnancy (r
      = 0.90, p < 0.0001), in early pregnancy (r = 0.91, p < 0.0001), and in late
      pregnancy (r = 0.87, p = 0.0005) and between leptin and oxygen consumption before
      pregnancy (r = 0.80, p = 0.004), in early pregnancy (r = 0.92, p < 0.0001), and
      in late pregnancy (r = 0.62, p = 0.06). When oxygen consumption was adjusted for
      maternal and fetal tissue mass, a significant negative correlation was found
      between leptin and oxygen consumption before pregnancy (r = -0.96, p < 0.0001),
      in early pregnancy (r = -0.80, p = 0.0034), and in late pregnancy (r = -0.70, p =
      0.02). CONCLUSION: We conclude that leptin increases significantly during early
      pregnancy before any major changes in body fat and resting metabolic rate. These
      data suggest that pregnancy represents a leptin-resistant state.

PMID- 9609577
TI  - Ultrasonographic bone velocity in pregnancy: a longitudinal study.
AB  - OBJECTIVE: Longitudinal changes in bone mass were evaluated with use of
      ultrasonography and bone remodeling markers in 40 normal pregnant women in
      relation to their calcium intake. STUDY DESIGN: The study took place at the
      University of Alcala Hospital in Madrid. Biochemical markers of bone remodeling
      and ultrasonographic bone propagation velocity in the proximal phalanxes of
      fingers 2 to 5 were measured in all three trimesters of pregnancy. Wilcoxon,
      unpaired and paired t tests, and analysis of variance were used. RESULTS:
      Ultrasonographic bone propagation velocity (meters per second) was lower in the
      second and third trimesters of pregnancy (p < 0.0001) compared with the
      respective preceding trimesters and in the third trimester in the overall group
      of pregnant women. Tartrate-resistant acid phosphatase and alkaline phosphatase
      levels increased significantly (p < 0.0001) in parallel with the ultrasonographic
      bone propagation velocity decrease. CONCLUSIONS: Gestation was accompanied by a
      reduction in ultrasonographic bone propagation velocity that was greater in women
      with low calcium intake.

PMID- 9609578
TI  - Father's effect on infant birth weight.
AB  - OBJECTIVE: We sought to determine whether paternal size at birth and during young
      adulthood influences the birth weight of the offspring. STUDY DESIGN: This
      historic cohort study followed up girls born in Copenhagen during 1959 to 1961.
      Their pregnancies in 1974 to 1989 were traced through the Danish Population
      Register, and the Personal Identification Numbers of the fathers of the children
      were obtained. Paternal birth weight was obtained from midwifery records and
      adult stature from military draft records. RESULTS: Compared with fathers who
      weighed at least 4 kg at birth, fathers who weighed 3 to 3.99 kg at birth had
      infants who were 109 gm lighter, and fathers who weighed <3 kg had infants who
      were 176 gm lighter after adjustment for maternal birth weight and adult stature,
      smoking, and medical and socioeconomic factors. After adjustment, fathers in the
      lowest quartile of adult body mass index had infants that were 105 gm lighter
      than those of fathers in the highest quartile. Both paternal birth weight and
      adult body mass index exhibited significant trends in association with infant
      birth weight. CONCLUSION: Independently of maternal size, the father's physical
      stature, particularly his own size at birth, influences the birth weight of his
      children.

PMID- 9609579
TI  - Activation of large-conductance potassium channels in pregnant human myometrium
      by pinacidil.
AB  - OBJECTIVE: The aim was to investigate the effects of the potassium-channel opener
      pinacidil on single uterine potassium channels and the contribution of the latter
      to pinacidil-induced myometrial relaxation. STUDY DESIGN: Myometrial strips and
      freshly dispersed uterine myocytes were prepared from the myometrial biopsy
      samples of women undergoing elective, nonlabor caesarean section at term
      gestation. RESULTS: In isometric tension experiments pinacidil potently relaxed
      pregnant nonlabor human myometrial strips, with an agonist concentration yielding
      the half maximal response of 0.4 +/- 0.1 micromol/L. This effect was antagonized
      by 500 nmol/L charybdotoxin. Application of 10 micromol/L glibenclamide also
      inhibited the pinacidil-induced relaxation. Coapplication of charybdotoxin (500
      nmol/L) and glibenclamide (10 micromol/L) produced a biphasic curve, which was
      fitted to a two-site model with values for agonist concentration yielding the
      half maximal response of 0.6 +/- 0.2 micromol/L and 189.7 +/- 0.8 micromol/L.
      Large-conductance calcium-dependent potassium channel activity was dramatically
      increased after application of pinacidil (between 10 and 100 micromol/L) to both
      inside-out and outside-out patches. The activation required the presence of
      calcium ions at the intracellular aspect of the membrane. Charybdotoxin but not
      glibenclamide blocked pinacidil-induced unitary large-conductance calcium
      dependent potassium channel activity. CONCLUSION: Pinacidil-mediated relaxation
      of human pregnant myometrial strips may be partially attributable to the opening
      of uterine large-conductance calcium-dependent potassium channels in addition to
      adenosine triphosphate potassium channel activation. Drugs with specific
      potassium channel-activating properties may have important clinical application
      as novel tocolytics in the treatment of preterm labor.

PMID- 9609580
TI  - The Preterm Prediction Study: recurrence risk of spontaneous preterm birth.
      National Institute of Child Health and Human Development Maternal-Fetal Medicine
      Units Network.
AB  - OBJECTIVE: We sought to estimate the risk of spontaneous preterm birth in parous
      women by use of obstetric history, fetal fibronectin, and sonographic cervical
      length. STUDY DESIGN: The probability of spontaneous preterm birth before 35
      weeks' gestation was estimated from a logistic regression model with data from
      1282 parous women analyzed according to gestational age at the most recent prior
      delivery (prior preterm birth at 18 to 26 weeks, 27 to 31 weeks, 32 to 36 weeks,
      and > or = 37 weeks' gestation), fetal fibronectin status (positive = > or = 50
      ng/dl), and cervical length by percentile groups (< or = 10th = < or = 25 nm,
      10th to 50th = 26 to 35 mm, and > 50th = > 35 mm) measured at 22 to 24 weeks'
      gestation. Fibronectin and cervical length results were blinded for clinical
      care. RESULTS: Among fetal fibronectin positive women with a prior preterm birth,
      the estimated recurrence risk of preterm birth < 35 weeks' gestation was
      approximately 65% when the cervix was < or = 25 mm, 45% when the cervix was 26 to
      35 mm, and 25% when the cervix was > 35 mm at 24 weeks' gestation. For fetal
      fibronectin negative women with a prior preterm birth, the recurrence risk was
      25% when the cervix was < or = 25 mm, 14% when the cervix was 26 to 35 mm, and 7%
      when the cervix was > 35 mm. The risk of preterm birth was increased among women
      with a history of preterm delivery but was not influenced by the gestational age
      at delivery of the most recent preterm birth. CONCLUSION: The recurrence risk of
      spontaneous preterm birth varies widely according to fetal fibronectin and
      cervical length. Cervical length and fetal fibronectin results had distinct and
      significant effects on the recurrence risk of preterm birth. Predicted recurrence
      risk is increased by twofold to fourfold in women with a positive compared with a
      negative fetal fibronectin, and it increases as cervical length shortens in both
      fetal fibronectin-positive and fetal fibronectin-negative women. These data may
      be useful to care for women with a history of preterm birth and to design studies
      to prevent recurrent premature delivery.

PMID- 9609581
TI  - The effect of oral terbutaline on maternal glucose metabolism and energy
      expenditure in pregnancy.
AB  - OBJECTIVE: Terbutaline, a selective beta2-agonist, is a frequently used tocolytic
      known to affect maternal metabolism. The purpose of this study was to evaluate
      the effect of oral terbutaline on maternal glucose metabolism and energy
      expenditure. STUDY DESIGN: Six healthy pregnant women with normal glucose
      tolerance were evaluated between 30 and 34 weeks' gestation. Oral terbutaline was
      administered to determine the effects on hepatic glucose production with [6
      6(2)H2] glucose tracer, insulin sensitivity (hyperinsulinemic-euglycemic clamp),
      and energy expenditure (indirect calorimetry). Terbutaline, insulin, and glucagon
      levels were also obtained. Subjects were randomly assigned to either oral
      terbutaline 5 mg every 6 hours for 24 hours or no medication. Repeat studies were
      conducted 1 week apart, each subject serving as her own control. RESULTS: In the
      basal state terbutaline was associated with a trend toward increased basal
      glucose levels (81.6 +/- 6.6 vs 93.7 +/- 12.0 mg/dl, p = 0.06) but no significant
      increase in hepatic glucose production (3.2 +/- 0.3 vs 3.6 +/- 0.4 mg/kg fat-free
      mass/min, p = 0.23). However, there was a significant increase in basal insulin
      concentration (17.6 +/- 9.2 vs 25.6 +/- 10.4 microU/ml, p = 0.02). There was a
      28% decrease in insulin sensitivity as measured by the glucose infusion rate
      during the euglycemic clamp plus residual hepatic glucose turnover (5.78 +/- 1.91
      vs 4.16 +/- 1.49 mg/kg fat-free mass/min, p = 0.005). Glucagon concentration was
      significantly decreased both in the basal state (163 +/- 26 vs 144 +/- 27 pg/ml,
      p = 0.0007) and during the clamp (144 +/- 27 vs 133 +/- 27 pg/ml, p = 0.003).
      Basal oxygen consumption increased 9% (270 +/- 49 vs 294 +/- 50 ml oxygen/min, p
      = 0.007) and caloric expenditure 14% (1.32 +/- 0.23 vs 1.50 +/- 0.31 kcal/min, p
      = 0.025) or 260 kcal/day with terbutaline. CONCLUSION: Decreased peripheral
      insulin sensitivity, and to a lesser degree increased endogenous glucose
      production, may represent the pathophysiology of abnormal glucose tolerance
      observed in many women treated with oral terbutaline. Common side effects such as
      tremors and tachycardia experienced by many women on a regimen of terbutaline are
      consistent with our finding of a significant increase in basal energy
      expenditure.

PMID- 9609582
TI  - Uterine artery blood flow velocity waveforms in pregnant women with mullerian
      duct anomaly: a biologic model for uteroplacental insufficiency.
AB  - OBJECTIVE: The purpose of this study was to determine whether there are
      demonstrable alterations in uterine artery blood flow in pregnant women with
      mullerian duct anomaly. STUDY DESIGN: Flow velocity waveforms obtained from the
      placental and nonplacental uterine arteries were studied at 18 to 24 weeks'
      gestational age in 15 pregnant women with mullerian duct anomaly and in 30
      controls. The systolic/diastolic ratios were compared and correlated with the
      degree of placental laterality and perinatal outcome. RESULTS: Systolic/diastolic
      ratio in the uterine artery was abnormal in 80% of the cases and in 10% of
      controls (p < 0.0001). A completely lateral placenta was found in 10 of 15 women
      of the study group and only in 1 of the 30 controls (p < 0.0001). Women with
      mullerian duct anomaly had higher systolic/diastolic ratios in the nonplacental
      uterine artery than those with a normal uterus (median 4.3, range 2.0 to 7.4 vs
      median 2.8, range 2.0 to 4.0; p < 0.001). Twelve of 15 women of the study group
      had poor perinatal outcome compared with 4 of the 30 controls (p < 0.001). Among
      those women with poor perinatal outcome, 11 of 12 (92%) in the study group and
      only 1 of the 4 (25%) in the control group had an abnormal systolic/diastolic
      ratio in the uterine arteries (p < 0.05). CONCLUSION: There is a clear
      association between placental laterality and high systolic/diastolic ratio in the
      nonplacental uterine artery in pregnant women with mullerian duct anomaly who had
      poor perinatal outcome. This finding suggests that unilateral placental
      implantation could lead to functional exclusion of one uterine artery from the
      uteroplacental circulation and could explain pregnancy complications in women
      with developmental fusion defects of the uterus.

PMID- 9609583
TI  - Experience with oral methylprednisolone in the treatment of refractory
      hyperemesis gravidarum.
AB  - OBJECTIVE: Our purpose was to describe the effect of oral methylprednisolone on
      the course of refractory hyperemesis gravidarum. STUDY DESIGN: Patients with
      intractable hyperemesis gravidarum were candidates for oral methylprednisolone.
      Forty-eight milligrams per day was given for 3 days followed by a tapering dose
      over 2 weeks. If vomiting recurred after 2 weeks of therapy or during tapering,
      the medication was restarted or extended but not longer than 1 month total.
      RESULTS: Seventeen of 18 patients (94%) were free of vomiting and were able to
      tolerate a regular diet within 3 days. Seven did not have further symptoms during
      their pregnancies. Nine vomited during or after tapering, but 7 of these
      responded to extension or reinstitution of therapy. Four of 6 patients on total
      parenteral nutrition at the start of therapy had a complete response within 3
      days. CONCLUSIONS: A short course of oral methylprednisolone appears to be a
      reasonable therapeutic alternative for intractable hyperemesis.

PMID- 9609584
TI  - Pregnant women with impaired tolerance to an oral glucose load in the afternoon:
      evidence suggesting that they behave metabolically as patients with gestational
      diabetes.
AB  - OBJECTIVE: In previous studies we observed the existence of a circadian variation
      of the blood glucose response to oral glucose in pregnant women with higher
      values at 4 PM. Some women with increased risk of diabetes with normal oral
      glucose tolerance tests at 8 AM also had values above maximum normal levels at 4
      PM. The aim of this trial was to determine the clinical significance of this
      impaired tolerance in the afternoon. STUDY DESIGN: Seventy-seven pregnant women
      with normal risk of diabetes (65 of normal weight and 12 overweight), 75 with
      increased risk of diabetes (26 overweight), and 12 patients with gestational
      diabetes were incorporated in the study. All women underwent two oral glucose
      tolerance tests (1.5 gm/kg) at 31 to 32 weeks' gestation at 8 AM and 4 PM with a
      1-week interval. At 33 weeks' gestation a whole-day blood glucose profile was
      performed with usual food intake; samples were withdrawn before each meal and at
      30, 60, and 120 minutes after each meal. The weight of the newborns was recorded.
      RESULTS: (1) Results of oral glucose tolerance tests confirmed a circadian
      variation of the response in all groups; (2) 37 women with increased risk of
      diabetes had higher values after oral glucose tolerance testing than the normal
      threshold at 4 PM but not at 8 AM; (3) among women with normal risk of diabetes
      all values were within the normal range despite the circadian variation; (4)
      blood glucose levels during whole-day profiles were normal in women with normal
      risk of diabetes and with increased risk of diabetes with normal oral glucose
      tolerance testing at 4 PM, whereas all women with increased risk of diabetes and
      impaired tolerance in the afternoon showed hyperglycemic episodes; (5) the
      percentage of newborns with high weight (>90th percentile) among women with
      increased risk of diabetes and abnormal oral glucose tolerance tests at 4 PM was
      similar to the percentage found in women with gestational diabetes and much
      higher than the one observed in women with normal oral glucose tolerance tests in
      the afternoon. CONCLUSIONS: The impairment of the response to oral glucose
      tolerance testing seen in some patients with increased risk of diabetes at 4 PM
      but not at 8 AM seems of clinical significance in view of the abnormal whole-day
      blood glucose profile these women had and the weights of the newborns.

PMID- 9609585
TI  - The clinical utility of serum uric acid measurements in hypertensive diseases of
      pregnancy.
AB  - OBJECTIVE: Our purpose was to evaluate the clinical utility of serum uric acid
      measurements in the hypertensive diseases of pregnancy. STUDY DESIGN: We
      performed a nested case-control study to assess the clinical utility of serum
      uric acid measurements in women with hypertensive diseases of pregnancy. We
      identified 344 women who had serum uric acid measurements at term and categorized
      them into five diagnostic groups according to definitions of hypertensive
      diseases in pregnancy published by the National Working Group on Hypertension in
      Pregnancy: transient hypertension of pregnancy (n = 69), preeclampsia (n = 130),
      chronic hypertension (n = 23), chronic hypertension with superimposed
      preeclampsia (n = 29), and normal (n = 93). We compared the mean uric acid
      concentration for each group with use of a one-way analysis of variance and
      Scheffe's post hoc test and calculated the sensitivities and specificities in
      diagnosing preeclampsia as well as the likelihood ratios for serum uric acid
      values of 5.5, 6.0, and 6.5 mg/dl. We also examined the correlation between serum
      uric acid levels and several clinical outcome measures in women with hypertensive
      diseases of pregnancy. RESULTS: The mean serum uric acid values for women with
      preeclampsia (6.2 +/- 1.4 mg/dl) and transient hypertension (5.6 +/- 1.7 mg/dl)
      were significantly higher than those of controls (4.3 +/- 0.8 mg/dl, p < 0.05).
      The difference in mean serum uric acid values between women with chronic
      hypertension (4.9 +/- 1.0 mg/dl) and superimposed preeclampsia (5.8 +/- 1.4
      mg/dl) were not statistically significant. The likelihood ratio of having
      preeclampsia with a serum uric acid value of 5.5 mg/dl was 1.41 in gestational
      hypertension of pregnancy and 2.5 in chronic hypertension. With use of a receiver
      operator characteristic curve, we were unable to identify a serum uric acid value
      that could be used to differentiate various hypertensive diseases of pregnancy.
      There was a weak correlation between serum uric acid values and several clinical
      outcome measures of preeclampsia (r = 0.06 to 0.26). CONCLUSION: Although mean
      serum uric acid values are elevated in women with preeclampsia, the clinical
      utility of serum uric acid values in differentiating various hypertensive
      diseases of pregnancy appears to be limited. In the setting of chronic
      hypertension, however, a serum uric acid level of > or = 5.5 mg/dl could identify
      women with an increased likelihood of having superimposed preeclampsia.

PMID- 9609586
TI  - Lipid peroxide and vitamin E patterns in pregnant women with different types of
      hypertension in pregnancy.
AB  - OBJECTIVES: We sought to evaluate the circulating levels of lipid peroxides and
      vitamin E and the placental levels of lipid peroxides in pregnant women with
      different types of hypertension. STUDY DESIGN: Lipid peroxides were measured in
      serum and placental tissue by the thiobarbituric acid method and high-pressure
      liquid chromatography, and vitamin E was measured by high-pressure liquid
      chromatography. The patients studied were 36 healthy pregnant women and 92 women
      with hypertension classified as having mild gestational hypertension (n = 28),
      severe gestational hypertension (n = 10), preeclampsia (n = 34), and chronic
      hypertension (n = 20). RESULTS: Lipid peroxides in serum and placental tissue
      were significantly increased, and vitamin E levels in serum were significantly
      decreased in women with severe gestational hypertension and preeclampsia compared
      with controls. The groups of mild gestational hypertension or chronic
      hypertension had similar values of lipid peroxides or vitamin E as controls.
      CONCLUSIONS: Our results suggest that the category of gestational hypertension
      may be composed of at least two entities with different pathophysiology and
      support the concept of nonproteinuric preeclampsia.

PMID- 9609587
TI  - Cocaine augments contractility of the pregnant human uterus by both adrenergic
      and nonadrenergic mechanisms.
AB  - OBJECTIVE: Our purpose was to evaluate the mechanisms of cocaine's effect on both
      spontaneous and agonist-induced contractility of pregnant human myometrium. STUDY
      DESIGN: Myometrium was obtained from 42 women at term who were undergoing
      cesarean section. Myometrial strips were suspended in contraction baths and
      isometric contractions were measured. Tissue was exposed to various combinations
      of cocaine, prazosin, desipramine, benzoylecgonine, and procaine. Spontaneous
      contractility and the contractile responses to increasing concentrations of
      methoxamine and oxytocin were measured and compared. RESULTS: Cocaine increased
      spontaneous myometrial contractility by more than threefold. Prazosin, an alpha
      adrenergic antagonist, blocked this effect only for the first 35 minutes of
      exposure. The cumulative concentration-response to the alpha-adrenergic agonist
      methoxamine was increased by cocaine in terms of both sensitivity and maximal
      response. The maximal response to oxytocin, but not the sensitivity, was
      increased by cocaine by an effect that could not be blocked by prazosin.
      CONCLUSION: Cocaine augments spontaneous and agonist-induced contractility of
      pregnant human myometrium by mechanisms that appear to be both alpha-adrenergic
      and nonadrenergic in nature.

PMID- 9609588
TI  - Dilatation of the urinary tract during pregnancy: proposal of a curve of maximal
      caliceal diameter by gestational age.
AB  - OBJECTIVE: Dilatation of the urinary tract is common during pregnancy, but the
      limits between physiologic and pathologic dilatation are unknown. Our purpose was
      to establish the pattern of physiologic urinary tract dilatation during
      pregnancy. STUDY DESIGN: This was a cross-sectional study. The maximal caliceal
      diameter was measured by ultrasonography at different weeks' gestational age in
      1506 pregnant and 181 postpartum women. A curve with the 90th, 75th, and 50th
      percentiles was drawn for each kidney. RESULTS: Fifty-three (6%) pregnant and
      postpartum women had some degree of dilatation. The right kidney was more
      frequently and severely affected, as were nulliparous women. The 90th percentile
      of maximal caliceal diameter of the right kidney increased about 0.5 mm/wk up to
      24 to 26 weeks, about 0.3 mm/wk up to 31 to 32 weeks, and remained stable until
      term. The left maximal caliceal diameter attained 8 mm around week 20 to 24 and
      remained stable until term. Only 6% had dilatation in the postpartum period.
      CONCLUSION: A normal curve of dilatation of the urinary tract is proposed.

PMID- 9609589
TI  - Effects of hormone replacement therapy on the endometrium and lipid parameters: a
      review of randomized clinical trials, 1985 to 1995.
AB  - The association between unopposed estrogen replacement therapy and endometrial
      hyperplasia and endometrial cancer in nonhysterectomized postmenopausal women is
      well known, and studies have suggested that the addition of progestin to the
      regimen reduces the risk of hyperplasia and cancer. The effect of estrogen plus
      progestin hormone replacement therapy on the lipid profile has also been
      extensively studied. To determine the extent of the effects of hormone
      replacement therapy on the endometrium and lipid parameters and to provide an
      overview of these studies, we reviewed 10 years of English language publications.

PMID- 9609590
TI  - Clinical value of intrapartum fetal pulse oximetry in cases complicated with
      meconium-stained amniotic fluid.

PMID- 9609591
TI  - Rapid prenatal detection of aneuploidies by fluorescent polymerase chain
      reaction.

PMID- 9609592
TI  - Metabolic acidosis and newborn complications: is a univariate threshold
      appropriate?

PMID- 9609593
TI  - Apgar scores.

PMID- 9609594
TI  - Breech delivery protocol.

PMID- 9609595
TI  - Fractured clavicle and birth trauma.

PMID- 9609596
TI  - Scientific problems with a noncausal artifact.

PMID- 9609597
TI  - Factor V Leiden--a novel etiology of the long-standing thrombosis theory for
      recurrent pregnancy loss.

PMID- 9609598
TI  - Towards better recognition of urogenital aging. Proceedings of the 8th
      International Congress on the Menopause held on November 5, 1996, in Sydney,
      Australia. Chairman's introduction.

PMID- 9609599
TI  - Urogenital aging--a hidden problem.
AB  - Urogenital problems in the elderly female population are experienced by one third
      of women from the age 50 years and onward. Symptoms from the lower urinary tract
      include incontinence, urethritis, and recurrent urinary tract infections.
      Atrophic changes within the bladder neck and urethra could be corrected by
      estrogen administration even at doses so low that endometrial proliferation is
      avoided. Hence such estrogens could be given without progestogen comedication.
      Control of micturition is a complex process of which estrogen deficiency is only
      one of several factors. The aging process with subsequent changes in membrane
      permeability, neuromuscular function, and collagen synthesis contributes to the
      local problems of control of micturition. In addition, the central control may
      also be affected by degenerative changes of the nervous system. Vaginal symptoms
      comprise dryness of vagina, dyspareunia, and recurrent vaginitis often followed
      by a foul odor and discharge. The microflora with lactobacilli and low pH as seen
      in fertile women is gradually replaced by a mixed germ flora including several of
      the pathogenic organisms common in urinary tract infections. Vaginal pH increases
      from around 4 to between 6 and 7. It is a puzzling fact that the urogenital
      tissues seem to be more "sensitive" to estrogens than other tissues.
      Conformational changes of the estrogen receptor(s) brought about by the local
      cytokine milieu is one possibility to explain the situation. The systemic
      absorption of low-dose estrogen preparations is dependent on the status of the
      vaginal mucosa. Absorption is high when the vaginal mucosa is atrophic and
      gradually decreases (but not to zero) as the vaginal mucosa matures under
      estrogen influence.

PMID- 9609600
TI  - The female perspective: women's attitudes toward urogenital aging.
AB  - Different perspectives toward symptoms of urogenital aging exist among
      postmenopausal women, influenced by social and cultural factors, but one constant
      is that women rarely feel able to discuss urogenital problems freely--with their
      physicians, husbands, or friends. European women >55 years old were brought up to
      prize "modesty" and to consider urogenital symptoms as private matters that the
      woman must solve herself. Sexuality in older age groups is recognized as
      important, but many postmenopausal women are reluctant to complain of
      deteriorating sex lives. In spite of a different view of the menopause, similar
      reticence is found in Japan. Physicians need to be better equipped to improve
      communications between themselves and their postmenopausal patients.

PMID- 9609601
TI  - Urogenital aging--creation of improved awareness.
AB  - Urogenital aging is given a low priority in the medical community and is an
      entity not well known to the general public. Many women are not aware of the
      possible disorders of the lower urinary tract and the vagina because of estrogen
      deficiency. These changes are perceived often as a normal part of the general
      aging process not associated with the possibility of medical attention,
      diagnosis, and treatment. Access to the information that certain urogenital
      dysfunctions, in particular incontinence, and vaginal discomfort respond to
      estrogen replacement therapy is not available for every woman. In addition,
      physicians and patients may hesitate to address these issues because of feelings
      of shame and embarrassment, feelings commonly encountered and specific for the
      complex of urogenital aging. Educational efforts and promotion of information
      with use of various media might help to improve knowledge and remove the taboo
      attached to urogenital aging in both health care providers and the general
      public. Thus a better understanding of urogenital aging would be achieved and the
      potential of estrogen replacement extended.

PMID- 9609602
TI  - The clinical platform for the 17beta-estradiol vaginal releasing ring.
AB  - All women, regardless of race, culture, or socioeconomic background, experience
      urogenital atrophy as a result of hypoestrogenism from the menopause. As women go
      through the aging cycle, their vaginal and urethral epithelium become
      progressively deprived of estrogen and the tissue loses epithelial thickness,
      rugation, moisture, vasculature, and elasticity. The pH increases to above 5,
      infections in the urinary tract and vagina become more prevalent and cytologic
      study reflects loss of estrogen by a decrease in superficial cells and an
      increase in basal and parabasal cells. Replacement of estrogen to reverse these
      changes is the standard of care, with recent attention focused on the local
      delivery of estrogen by the vaginal route. The first vaginal ring delivery system
      of estrogen to the urogenital tract recently has been introduced, with the data
      confirming efficacy and safety of this delivery method for the treatment of
      urogenital atrophy. In addition, data on the 17beta-estradiol-releasing ring also
      support excellent patient acceptance of this local vaginal delivery system of
      estrogen therapy.

PMID- 9609604
TI  - Hypereosinophilia and markedly elevated immunoglobulin E in a 3-year-old child.

PMID- 9609603
TI  - Principles of current adult HIV pharmacotherapy.
AB  - OBJECTIVE: To provide a concise review of the current approach to the clinical
      use of the available drugs for HIV infection. DATA SOURCES: Recent "state of the
      art" publications and key reference articles. CONCLUSIONS: Prognostic and
      monitoring parameters for HIV infection have been established based on new
      insights into the life-cycle of HIV and novel virologic techniques. Three groups
      of antiretrovirals are now available for general use. Familiarity with these
      drugs, their pharmacokinetics, side effects, and drug-drug interactions, as well
      as with the specific milieu of each individual patient is crucial for the
      successful management of HIV infection.

PMID- 9609605
TI  - Allergic bronchopulmonary mycosis to Fusarium vasinfectum in a child.
AB  - BACKGROUND: A 12-year-old boy with asthma and 6 years of recurrent pneumonias who
      had normal serum immunoglobulin concentrations was suspected of having allergic
      bronchopulmonary aspergillosis (ABPA). OBJECTIVE: To search for and secure a
      fungal etiology for a child who did not have ABPA but was suspected of having an
      allergic bronchopulmonary mycosis. METHODS: Immediate skin testing with fungal
      extracts, high resolution computerized tomography, and establishment of an ELISA
      procedure to detect serum IgE and IgG antibodies to Fusarium vasinfectum.
      RESULTS: Immediate skin reactivity was present for Fusarium, Cladosporium,
      Helminthosporium, and Aspergillus fumigatus. The ELISA demonstrated serum IgE and
      IgG antibodies to Fusarium vasinfectum 8.5 and 5.6 times nonatopic control sera.
      CONCLUSIONS: This 12-year-old with asthma has sufficient criteria for a diagnosis
      of allergic bronchopulmonary mycosis (ABPM) to Fusarium vasinfectum.
      Bronchiectasis was not present despite recurrent pneumonias and hemoptysis. This
      case appears to be the first pediatric example of ABPM to Fusarium species, a
      fungus more recognized for causing rotting of tomatoes and melons than human
      disease.

PMID- 9609606
TI  - Methacholine provocations do not reveal sensitivity to strong scents.
AB  - BACKGROUND: It is common among patients with asthma to report sensitivity to
      strong scents. Provocations with methacholine are often used to verify this
      sensitivity. OBJECTIVE: To evaluate the significance of methacholine provocations
      in asthmatic patients complaining about sensitivity to strong scents, we compared
      sensitivity to methacholine and reactions to provocation with perfume. METHODS:
      Ten asthmatic patients having a PC20 less than 2 mg methacholine/mL were provoked
      with perfume or saline on four occasions. On two occasions, the patients wore a
      nose clip and underwent provocations with perfume for 5 and 30 minutes,
      respectively. On one occasion, the patients were provoked with perfume but
      without a nose clip for five minutes. All patients were also subjected to
      provocation with a placebo (saline). They were asked to estimate their
      sensitivity to strong scents in connections with symptoms of asthma. RESULTS: No
      changes in lung function occurred after any of the provocations with perfume
      compared with the baseline or with placebo. Although all patients were very
      sensitive to methacholine, no relationship was found to their reported
      sensitivity to strong scents in connection with asthmatic symptoms. CONCLUSION:
      In this study, asthmatic patients who were very sensitive to methacholine were
      not affected by provocations with perfume. One may therefore question the value
      of provocations with methacholine in patients complaining of symptoms after
      contact with strong scents.

PMID- 9609607
TI  - A controlled trial of twice daily triamcinolone oral inhaler in patients with
      mild-to-moderate asthma.
AB  - BACKGROUND: National and international guidelines recommend inhaled anti
      inflammatory medications for patients with all but the mildest forms of asthma.
      Patients may also be more compliant with twice daily dosing. OBJECTIVE: To
      evaluate the efficacy and safety of triamcinolone acetonide (triamcinolone
      acetonide), 400 microg bid, in mild-to-moderate asthma patients. METHODS: A
      multicenter, randomized, double-blind, placebo-controlled study with a 7- to 21
      day baseline and 6-week treatment period. Adult mild-to-moderate asthma patients
      poorly controlled by beta2-agonists alone were randomized to receive placebo (48)
      or triamcinolone acetonide (53). Patients recorded daytime and nighttime asthma
      symptoms, albuterol use, and morning and evening peak expiratory flow (PEF) rates
      on diary cards. Clinic spirometry measures included FEV1, FEF25-75%, FVC,
      FEV1/FVC, and PEF. RESULTS: Triamcinolone acetonide treatment resulted in
      improvement from baseline of 17% for FEV1 (P < .0001); 44% for albuterol use (P =
      .0009); 9% for FVC (P = .0185); 19% for PEF (P = .0011); 42% for FEF25-75% (P <
      .0001); 8% for FEV1/FVC (P = .0016); 36% for daytime, 39% for nighttime, and 38%
      for total asthma symptoms (P < or = .0001); and 12% for morning, and 10% for
      evening PEF (P < or = .001). These changes were highly significant when compared
      with placebo (P < or = .0185). Significant improvement for all variables was
      demonstrated within 1 to 2 weeks of active treatment, and maintained for most
      variables over the 6-week treatment phase. Both treatments were well tolerated.
      Respiratory adverse events occurred more frequently with placebo; pharyngitis was
      reported more frequently with triamcinolone acetonide. CONCLUSIONS: Triamcinolone
      acetonide, administered twice daily, can effectively and safely treat patients
      with milder forms of asthma. In these patients, triamcinolone acetonide improves
      asthma symptoms and decreases the need for as-needed beta2-agonists.

PMID- 9609608
TI  - Clinical adverse effects of inhaled corticosteroids: results of a questionnaire
      survey of asthma specialists.
AB  - BACKGROUND: Inhaled corticosteroids are recognized as the mainstay of
      prophylactic anti-inflammatory therapy in patients with persistent asthma. In
      large multiclinic trials, the clinical adverse event profiles have been not
      significantly different than patients treated with placebo or other medications;
      however, in small studies evaluating very sensitive in vitro measurements of the
      hypothalamic pituitary adrenal axis there have been adverse laboratory events
      noted with moderate and high doses of inhaled steroids. OBJECTIVE: To survey
      asthma specialists in North America with regard to their personal clinical
      experience of adverse events with the use of inhaled corticosteroids. METHODS:
      Two hundred thirteen physicians specializing in the treatment of asthma responded
      to questionnaires asking their experiences with specific adverse clinical events
      that have the potential to occur after the use of inhaled corticosteroids (see
      appendix A for questionnaire). RESULTS: There was a 67% response rate for the
      questionnaire. Eighty percent of the respondents were allergists/immunologists
      and 20% were pulmonologists. The average length of time they had been in practice
      was 16 years. In general, side effects from inhaled steroids were seen very
      infrequently in the hands of these physicians in spite of the fact that they were
      primarily secondary or tertiary referral physicians for the treatment of asthma.
      The local oropharyngeal adverse events were seen 48% of the time on an occasional
      basis but only 3% of the time on a frequent basis. When spacers were used the
      oropharyngeal symptoms were reduced significantly. Skin changes such as bruising
      or thin skin were seen frequently 6% of the time and occasionally 24% of the time
      only. In general, these skin changes were found in elderly or middle-aged
      individuals. Weight gain was very unusually seen, as were adverse effects on bone
      (osteoporosis, fractures, growth problems, etc.). Hypothalamic pituitary axis
      abnormalities were seen quite infrequently and primarily in patients who had also
      received oral corticosteroids. CONCLUSIONS: This study shows that inhaled
      corticosteroids are generally safe in the treatment of asthma and are rarely
      associated with systemic side effects, as detected in routine clinical practice.

PMID- 9609609
TI  - Efficacy of aminophylline in the treatment of acute asthma exacerbation in
      children.
AB  - BACKGROUND: The role of aminophylline (ethylene diamine salt of theophylline) in
      the treatment of acute exacerbation of asthma has not been well established in
      children. OBJECTIVE: The aim of the study was to determine the additional
      therapeutic benefit of intravenous aminophylline in the treatment of children
      hospitalized for acute asthmatic exacerbation and treated with inhaled
      bronchodilators and glucocorticoid therapy. METHODS: Thirty-eight children aged
      from 2 to 16 years (mean age 5.64 +/- 3.31), admitted for acute exacerbation of
      asthma, participated in a prospective, randomized, double-blind, placebo
      controlled study. All the subjects received methylprednisolone, administered
      intravenously, and nebulized salbutamol. The treatment group received intravenous
      aminophylline therapy and the placebo group received 0.9% saline solution for 24
      hours. RESULTS: The number of salbutamol nebulizations needed and the clinical
      asthma scoring were recorded both at onset and at the end of 24 hours. There was
      no significant difference in either the mean number of nebulizations or the
      clinical asthma scores between the two groups (P = .7843, P = .8452). CONCLUSION:
      Intravenous aminophylline (ethylene diamine salt of theophylline) demonstrated no
      additional beneficial effect to the combination of beta adrenergic agonists and
      glucocorticoid treatment in acute asthma attack in children.

PMID- 9609611
TI  - Chlamydia pneumoniae and exacerbations of asthma in adults.
AB  - BACKGROUND: Chlamydia pneumoniae is a frequent causative agent of acute
      respiratory disease and has been recently reported as a possible cause of asthma.
      OBJECTIVE: We assessed the prevalence of C. pneumoniae infections in adult
      patients with acute exacerbations of asthma. METHODS: One hundred sixty-eight
      adult patients with acute exacerbations of asthma and 108 control subjects
      matched for age, sex, and smoking status were studied. Nasopharyngeal swab
      specimens were obtained from all subjects and analyzed by isolation in cell
      culture and polymerase chain reaction (PCR) test for C. pneumoniae. Serum samples
      were also obtained and tested for C. pneumoniae-specific antibodies by the
      microimmunofluorescence test. RESULTS: C. pneumoniae was isolated from two (1.2%)
      asthma patients and none from controls and detected by PCR from nine (5.4%) cases
      and one (0.9%) control. Both culture positive specimens were also positive in
      PCR. Further, serologic evidence of acute C. pneumoniae infection was present in
      15 (8.9%) of asthma patients and in three (2.8%) of controls (P = .048). The
      prevalence of C. pneumoniae-specific IgG and IgA was significantly higher in
      asthma cases than in controls (IgG > or = 1:16: 85.1% versus 67.6%, P = .001; IgA
      > or = 1:16: 47.6% versus 16.7%, P < .001). Mean titer of IgG and IgA was also
      significantly greater in asthma cases than in controls (IgG: 38.8 versus 18.1, P
      = .0001; IgA: 17.2 versus 6.1, P = .0001). CONCLUSIONS: Our data suggest that C.
      pneumoniae infection may trigger acute exacerbations of adult asthma.

PMID- 9609610
TI  - Comparison of efficacy and safety of cetirizine and ebastine in patients with
      perennial allergic rhinitis.
AB  - BACKGROUND: Cetirizine and ebastine are two second-generation histamine H1
      antagonists undergoing evaluation for treatment of perennial rhinitis. OBJECTIVE:
      The clinical efficacy and safety of once daily cetirizine 10 mg were compared
      with ebastine 10 mg in patients with perennial allergic rhinitis in a 4-week,
      double-blind, parallel-group, randomized, multicenter study. METHOD: Two hundred
      fourteen patients (120 females, 94 males, aged 17 to 70 years, mean 31.2 years)
      were selected on the basis of perennial allergic rhinitis history, positive skin
      test for perennial allergens and a minimum rhinitis symptom score of 6/12.
      Patients recorded nasal symptom severity (nasal stuffiness, nasal discharge,
      sneezing, and itching) once daily on diary cards using a rating scale of 0 (none)
      to 3 (severe). Clinicians made an overall evaluation after 4 weeks of treatment.
      An intent-to-treat-analysis was performed comparing cetirizine (106 patients) and
      ebastine groups (108 patients). RESULTS: The individual and total baseline
      symptom scores were comparable in both treatment groups. During the first week,
      the percentage mean decrease in the total nasal symptom score from baseline (sum
      of nasal stuffiness, discharge, sneezing, and itching) was significantly higher
      for cetirizine 46.2% than for ebastine 32.8% (P = .037). After 4 weeks of
      treatment, total symptom score improvement was 53.7% for cetirizine and 44.7% for
      ebastine (P = .12), and the clinician's overall evaluation showed that the
      percentage of symptom-free patients was significantly higher for cetirizine 17.8%
      than for ebastine 6.9% (P = .02). Cetirizine also significantly improved nasal
      stuffiness. An associated antiinflammatory effect is suggested. Commonly reported
      drug-related side effects were similar in both groups. CONCLUSION: This study
      shows that both antihistamines, cetirizine 10 mg and ebastine 10 mg once a day,
      improved symptom scores of patients with perennial allergic rhinitis. Cetirizine,
      however, provided faster improvement and total relief in a greater number of
      patients after 4 weeks.

PMID- 9609612
TI  - Seasonal variation of IgG subclass antibodies to house dust mite in sera from
      mite-sensitive asthmatic patients.
AB  - BACKGROUND: House dust mite is an important cause of bronchial asthma. Seasonal
      variation of environmental house dust mite allergen levels and the specific IgE
      antibody to house dust mite have been reported. OBJECTIVE: We studied the changes
      in IgG subclass antibodies to house dust mite associated with seasonal variation
      of house dust mite allergen levels in houses of mite-sensitive asthmatic
      patients. METHODS: In 14 mite-sensitive asthmatic patients, house dust mite
      allergen (Der f 1) contents in bedding were measured monthly, and IgG subclass
      antibodies to house dust mite, Dermatophagoides farinae (D. farinae), were
      determined by enzyme-linked immunosorbent assay (ELISA) every 3 months from July
      to December. RESULTS: The concentration of Der f 1 in dust from bedding reached
      maximum levels in August and September, and significantly decreased in November
      and December compared with August and September (P < .05). Levels of D. farinae
      specific IgG4 antibodies significantly decreased in December compared with
      September (P < .05) with no statistically significant change between September
      and June (P > .05). Levels of D. farinae-specific IgG2 antibodies decreased
      significantly in December compared with June (P < .05). The levels of IgG1 and
      IgG3 antibodies to D. farinae showed no significant differences during the study
      period. CONCLUSION: These findings suggest that seasonal changes in natural
      exposure to house dust mite allergen might lead to concurrent changes in specific
      IgG4 antibodies to house dust mite in mite-sensitive asthmatic patients and each
      IgG subclass antibodies to house dust mite might have a different kinetics.

PMID- 9609613
TI  - Probenecid hypersensitivity in AIDS: a case report.
AB  - BACKGROUND: Cidofovir plus probenecid is a new therapeutic alternative for
      refractory cytomegalovirus and acyclovir-resistant herpes infections in AIDS
      patients. Probenecid is used in conjunction with the antiherpetic medication
      (cidofovir) in order to reduce the incidence of nephrotoxicity by cidofovir.
      OBJECTIVE: To present therapeutic alternatives for successful administration of
      probenecid to AIDS patients who develop a hypersensitivity reaction to the
      medication. METHODS AND RESULTS: We describe a patient with AIDS who was being
      treated with the cidofovir/probenecid combination for a peri-anal acyclovir
      resistant herpetic infection. The patient subsequently developed a cutaneous
      hypersensitivity reaction to probenecid alone. A pretreatment regimen consisting
      of prednisone, H1 and H2 blockers was administered before the dosing of
      probenecid in order for the patient to continue with the antiviral therapy.
      CONCLUSION: Cutaneous hypersensitivity reactions to probenecid may be seen more
      frequently with the increasing use of cidofovir in AIDS patients. Our pre
      treatment protocol is one therapeutic alternative to be considered in order to
      continue with probenecid.

PMID- 9609614
TI  - Immunologic changes during immunotherapy in asthmatic children: increased IL-13
      and allergen-specific IgG4 antibody levels.
AB  - BACKGROUND: The prevalence of allergic diseases such as asthma, allergic
      rhinitis, and atopic diseases has increased in recent years. Immunotherapy with
      allergens is a treatment documented to have an effect on regulating cytokine
      production and allergen-specific antibody production. OBJECTIVE: The aim of this
      study was to further investigate immunologic changes during immunotherapy and to
      explore the possible more efficient approach of immunotherapy. METHODS: Asthmatic
      children receiving house dust mite immunotherapy were followed to learn
      immunologic parameters such as allergen-specific antibody levels, proliferative
      response of peripheral blood mononuclear cells, and cytokine change during
      immunotherapy. RESULTS: The data suggested (1) IgG4 anti-mite antibody increased
      8 months after immunotherapy while IgE antibody level remained the same; (2)
      allergen-induced, in vitro production of certain cytokines such as IL-4 and IL-10
      decreased after immunotherapy; (3) IL-13 (which can induce IgG4 and IgE antibody
      production by B cells) increased after immunotherapy. CONCLUSION: Although this
      needs more study, IL-13 might play an important role in the generation of IgG4
      blocking antibody during immunotherapy.

PMID- 9609615
TI  - Peripheral blood manifestations of T(H)2 lymphocyte activation in stable atopic
      asthma and during exercise-induced bronchospasm.
AB  - BACKGROUND: Recently, TH2 lymphocyte activation has been shown to play a key role
      in initiating and propagating the inflammatory response in asthmatic airways.
      This is manifest through increased numbers of "activated" CD25-(IL-2R)-bearing T
      helper cells and can be seen through the IL-5 driven recruitment of eosinophils
      and IL-4-mediated B-cell expression of CD23 (low affinity IgE receptor) and
      ultimately IgE production. OBJECTIVE: To gain a better understanding of the role
      of immune cells in asthma by describing the peripheral blood immune cell
      phenotypes in mild atopic asthma. METHODS: We enrolled 13 patients with mild
      atopic asthma and a group of seven nonatopic, nonasthmatic controls. Objective
      measures of lung function were obtained. The peripheral blood was analyzed by
      flow cytometry for specific cellular markers at rest and during the development
      of exercise induced bronchospasm. RESULTS: At rest the number of CD23-bearing B
      cells (169/mL versus 117/mL; P = .05) and the number of CD25-bearing T cells
      (355/mL versus 237/mL; P = .03) were increased in the asthma group. There was a
      linear relationship between these two lymphocyte subsets and the maximum
      voluntary ventilation at rest (r = 0.56, P = .01 and r = 0.57, P = .01). With the
      development of exercise-induced bronchospasm there was a significantly greater
      increase in CD23-positive B cells (96.7/mL versus 59.7/mL; P = .05) and CD25
      positive T cells (111.8/mL versus 45.1; P = .01) in the asthma group.
      CONCLUSIONS: These data indicate that TH2 lymphocyte activation is manifested by
      increased numbers of CD23-bearing B cells and CD25-bearing T cells in the
      peripheral blood of patients with stable mild atopic asthma. Further, these
      immune cell subsets correlate with markers of resting lung function and increase
      in the peripheral blood early after the development of exercise-induced
      bronchospasm.

PMID- 9609616
TI  - Delayed hypersensitivity to aminopenicillins is related to major
      histocompatibility complex genes.
AB  - BACKGROUND: Although in some cases delayed hypersensitivity may be observed, beta
      lactam antibiotics frequently induce immediate allergic IgE-mediated reactions
      with the specificity localized in the acyl-side chain structure. Generally,
      delayed immunologic reactions are related to sensitized T lymphocytes and major
      histocompatibility complex restricted. OBJECTIVE: To investigate the prevalence
      of HLA class I and II antigens in patients with delayed hypersensitivity to
      aminopenicillins in order to evaluate a relationship between major
      histocompatibility complex immune response genes and aminopenicillins
      hypersensitivity. METHODS: We assessed 24 patients with history of delayed
      hypersensitivity to aminopenicillins using (1) skin test with penicilloyl
      polylysine, minor determinant mixture, benzylpenicillin, amoxicillin, and
      ampicillin; (2) patch tests with benzylpenicillin, amoxicillin, and ampicillin;
      (3) RAST for penicilloyls G and V; and (4) oral challenges with amoxicillin,
      ampicillin, and penicillin V in 18/24 patients. All patients were typed by
      microlymphotoxicity standard test for HLA class I and II antigens. Statistical
      analysis by chi2 test 2 x 2 contingency tables, according to Svejgaard, were used
      for comparison between patients and random Italian population (522 subjects).
      RESULTS: In the patients group we found higher prevalence of HLA A2 (12/24 = 50%,
      RR = 6.76 P < .001, EF = 0.425), DRw52 (20/24 = 83.3%, RR = 9.28, P < .001, EF =
      0.74), and lower frequency of DR4 (3/24 = 12% ns). CONCLUSIONS: These data
      suggest that the immune mechanisms involved in adverse reactions to
      aminopenicillins in vivo are related to genetic markers of immune response and
      confirms that the presentation of penicillin-hapten determinants to lymphocyte is
      major histocompatibility complex restricted.

PMID- 9609617
TI  - Control of environmental tobacco smoke.

PMID- 9609618
TI  - Endopyelotomy revisited.

PMID- 9609619
TI  - Retrograde acucise endopyelotomy.

PMID- 9609620
TI  - Alpha-blockade therapy for benign prostatic hyperplasia: from a nonselective to a
      more selective alpha1A-adrenergic antagonist.
AB  - Benign prostatic hyperplasia (BPH) is very common in older men, causing symptoms
      that can markedly impair quality of life. Surgical treatment, typically
      transurethral resection of the prostate (TURP), is highly effective but can be
      costly and is associated with the risk for significant morbidity. Medical
      treatments for BPH are targeted toward reducing bladder outlet obstruction either
      by androgen blockade to reduce prostatic volume or alpha-adrenergic blockade to
      relax the smooth muscle tone of the prostate. In recent years, understanding of
      the sympathetic innervation of the prostate has improved. This has been
      paralleled by the development of alpha-adrenergic blocking agents, from
      nonselective alpha-antagonists, to selective alpha1-antagonists, to the more
      selective alpha1A-antagonists. It is anticipated that more specific agents will
      optimize the therapeutic effectiveness of alpha-adrenergic blockade in the
      prostate while reducing the side effects associated with alpha-adrenergic
      blockade in other areas of the body, such as the vascular system. This article
      reviews the evolution of alpha-blockade therapy in management of BPH, focusing on
      tamsulosin, an agent targeted toward the alpha1A-adrenoceptor that predominates
      in the prostate. Clinical trials in Europe and the United States have provided
      evidence that tamsulosin is effective at doses of 0.4 and 0.8 mg/day. At both
      doses, tamsulosin is associated with significant improvements in the American
      Urological Association symptom score and the mean and peak urinary flow rates as
      compared with placebo. This once-daily alpha1A-adrenergic antagonist is well
      tolerated, with a minimal potential for the side effects associated with alphas
      blocker therapy.

PMID- 9609621
TI  - Erectile dysfunction: therapy health outcomes.

PMID- 9609622
TI  - Comparison of radical prostatectomy and iodine 125 interstitial radiotherapy for
      the treatment of clinically localized prostate cancer: a 7-year biochemical (PSA)
      progression analysis.
AB  - OBJECTIVES: To evaluate the relative efficacy of brachytherapy to radical
      prostatectomy, we compared biochemical progression rates from a published series
      of men who underwent iodine 125 (125I) interstitial radiotherapy for localized
      prostate cancer to a similar group of men who underwent anatomic radical
      prostatectomy using appropriate end points. METHODS: Seventy-six men who
      underwent anatomic radical prostatectomy between 1988 and 1990 were carefully
      matched for Gleason score and clinical stage to a recently reported contemporary
      series of patients treated at another institution with 125I brachytherapy without
      adjuvant treatment. The definition of biochemical progression was a serum PSA
      level greater than 0.2 ng/mL after anatomic radical prostatectomy and greater
      than 0.5 ng/mL for brachytherapy-treated patients. RESULTS: The 7-year actuarial
      PSA progression-free survival following anatomic radical prostatectomy was 97.8%
      (95% confidence interval [CI], 85.6% to 99.7%) for this group of men selected to
      match the brachytherapy group, compared to 79% (95% CI not published) for men
      treated with 125I interstitial radiotherapy. CONCLUSIONS: Using comparative end
      points for biochemical-free progression, failure rates may be higher following
      125I interstitial radiotherapy compared to anatomic radical prostatectomy. These
      data provide a better comparison of biochemical progression than previously
      published studies and emphasize the need for caution in interpreting the relative
      efficacy of brachytherapy in controlling localized prostate cancer.

PMID- 9609623
TI  - Phase III multicenter placebo-controlled study of tamsulosin in benign prostatic
      hyperplasia. Tamsulosin Investigator Group.
AB  - OBJECTIVES: To evaluate the efficacy and safety of two once-daily doses of
      tamsulosin, the first selective alpha1A-antagonist studied in clinical trials.
      METHODS: Patients with benign prostatic hyperplasia (BPH) were randomized to
      receive either tamsulosin (0.4 and 0.8 mg/day) or placebo (n = 756). Primary
      efficacy parameters were improvement in the total American Urological Association
      (AUA) symptom score and peak urinary flow (Qmax). Secondary efficacy parameters
      were improvement in measurements at individual double-blind visits corresponding
      to the primary efficacy parameters; percentage of patients with a 3-mL/s increase
      in Qmax; total AUA irritative, obstructive, and bother scores; individual AUA
      symptom scores; total, irritative, obstructive, and individual Boyarsky symptom
      scores; average urinary flow rate and other uroflowmetric parameters; and
      investigator's global assessment. RESULTS: Statistically significant improvements
      in all efficacy parameters were observed in tamsulosin-treated compared with
      placebo-treated patients. Additionally, the 0.4-mg/day dose demonstrated a rapid
      onset of action (4 to 8 hours) based on Qmax after the first dose of double-blind
      medication. A review of the safety parameters demonstrated excellent tolerance at
      1 week after the initial 0.4-mg/day dose and continued tolerance during the
      additional 12 weeks of 0.4- and 0.8-mg/day dosing. The incidence of positive
      orthostatic test results in the tamsulosin groups was comparable to that observed
      in the placebo group. Adverse events were comparable in the 0.4-mg/day tamsulosin
      and placebo groups and were somewhat higher in the 0.8-mg/day tamsulosin group.
      CONCLUSIONS: Tamsulosin was effective, safe, and well tolerated in the target BPH
      population at both the 0.4- and 0.8-mg/day dose levels, without the blood
      pressure-lowering effects typical of nonselective alpha-adrenergic antagonists.

PMID- 9609624
TI  - Long-term evaluation of tamsulosin in benign prostatic hyperplasia: placebo
      controlled, double-blind extension of phase III trial. Tamsulosin Investigator
      Group.
AB  - OBJECTIVES: To evaluate the long-term efficacy and safety of once-daily
      tamsulosin (0.4 and 0.8 mg), a unique selective alpha1A-adrenoceptor antagonist
      in patients with benign prostatic hyperplasia (BPH). METHODS: This trial extended
      a 13-week, Phase III multicenter placebo-controlled, double-blind outpatient
      trial for an additional 40 weeks. Of 618 patients, 418 (68%) continued into the
      extension phase on the same double-blind medication and dose. The primary
      efficacy parameters were total American Urological Association (AUA) symptom
      score and maximum urinary flow (Qmax). RESULTS: The mean changes in AUA symptom
      score from baseline to end point were statistically significant in all groups (P
      <0.001). Significant improvements were observed in Qmax for both tamsulosin
      groups but not for the placebo group. The statistically significant improvements
      from baseline in efficacy parameters observed for each tamsulosin group at the
      end of the 13-week Phase III trial were maintained during the long-term extension
      phase. Tamsulosin at both dosages was well tolerated as maintenance therapy.
      Clinically significant orthostatic hypotension was not observed. Vital sign
      changes in either hypertensive or normotensive patients were not clinically
      significantly different across the three groups. CONCLUSIONS: Tamsulosin once
      daily at 0.4 or 0.8 mg was shown to be effective, safe, and well tolerated in the
      target BPH population during long-term use.

PMID- 9609625
TI  - Contrasting heating patterns and efficiency of the Prostatron and Targis
      microwave antennae for thermal treatment of benign prostatic hyperplasia.
AB  - OBJECTIVES: To determine the design and performance characteristics of two
      microwave antennae for use in thermal treatment of benign prostatic hyperplasia.
      METHODS: Prostatron and Targis antennae were subjected to detailed physical
      examination and measurement. The heating patterns generated by these two types of
      antennae were characterized in detail using tissue-equivalent phantoms.
      Measurements of return loss as a function of frequency were conducted to evaluate
      the capacity of the antennae for impedance matching. Percent reflected power was
      calculated from the return loss results to provide a relative measure of
      potential for efficient delivery of thermal energy. RESULTS: The Prostatron
      antenna was found to be a monopole design consisting of a coaxial cable with a
      3.3-cm length of inner conductor exposed at the tip. The Targis antenna was
      observed to be a dipole design with a 2.8-cm helical coil attached through a
      ground connection and a tap point to a coaxial cable. The heating pattern of the
      Targis antenna was symmetric; that of the Prostatron was asymmetric with
      substantial back heating along the catheter axis in the direction of the
      microwave power source. The mean extension of the 30 degrees C isotherm in the
      direction of the power source with the Prostatron antenna (71.5 mm; 95%
      confidence interval [CI], 63.4 to 79.6 mm) was 55% greater (P < 0.0005) than that
      with the Targis antenna (46.0 mm; 95% CI, 38.2 to 53.8 mm). Return loss with the
      Targis antenna declined sharply to a relative minimum value of -32.9 dB (95% CI, 
      73.8 to 8.0 dB) at 915 MHz, providing evidence of this antenna's capacity for
      impedance matching; little change was observed with the Prostatron in return loss
      over a frequency range 100 MHz above and below this antenna's standard operating
      frequency of 1296 MHz. The mean reflected power of the Targis antenna (0.4%; 95%
      CI, 0.0% to 1.4%) was lower by more than 20-fold (P = 0.036) than that of the
      Prostatron antenna (11.0%; 95% CI, 3.4% to 18.7%); thus, the potential for
      efficient operation was greater with the Targis than the Prostatron antenna.
      CONCLUSIONS: The Targis microwave antenna was found to provide a more targeted
      heating pattern and have a capacity for more efficient thermal energy delivery
      than the Prostatron antenna. These differences observed in vitro could
      potentially translate into clinical advantages in vivo, such as improved
      tolerability of microwave treatment, reduced risk of complications, greater
      thermoablative efficacy, and scalability.

PMID- 9609626
TI  - Laparoscopy for the acute abdomen in the postoperative urologic patient.
AB  - OBJECTIVES: Exploratory laparotomy offers the greatest diagnostic accuracy of
      intra-abdominal pathologic processes, but can be associated with significant
      morbidity. Laparoscopy provides diagnostic capabilities equivalent to that of
      open exploration, but with potentially less morbidity. We present 3 cases in
      which laparoscopy was used to diagnose and manage urologic patients with an acute
      abdomen in a postoperative period. METHODS: Three patients underwent laparoscopy
      between 1 and 14 days postoperatively for an acute abdomen (fever, elevated white
      blood cell count, and peritoneal signs). The initial procedures included a
      pubovaginal sling repair with fascia lata, endoscopic placement of a percutaneous
      gastrostomy tube, and a laparoscopic ureterolithotomy for a distal stone.
      RESULTS: In each of the 3 patients laparoscopy revealed misplacement or
      malfunction of a previously placed tube. In all cases, the patient was managed
      laparoscopically without the need for laparotomy. CONCLUSIONS: These cases
      demonstrate the feasibility of laparoscopy to provide diagnostic and therapeutic
      solutions to postoperative urologic patients presenting with an acute abdomen.

PMID- 9609627
TI  - Sixty adrenal masses of large dimensions: hormonal and morphologic evaluation.
AB  - OBJECTIVES: To evaluate the nature and function of adrenal masses of large
      dimensions (macrotumors). METHODS: Sixty consecutive patients (31 women, 29 men,
      age range 15 to 84 years) with adrenal masses 4.0 cm in diameter or larger (range
      4.0 to 15.0 cm) underwent morphologic study by computed tomography (CT); the
      majority also underwent 131-I-6beta-norcholesterol (131I-NC) or 131I-MIBG
      scintigraphy. Basal evaluation of glucocorticoids, mineralcorticoids, and
      catecholamines was performed in all patients, and in 38 cases determination of
      androgens was also made. In addition, on the basis of various clinical
      suspicions, a dynamic hormonal study was performed. RESULTS: Macrotumors were
      benign in 78.3% of cases and included pheochromocytomas (n = 17), nonfunctioning
      cortical adenomas (n = 12), and cortisol-secreting tumors (n = 7, Cushing's
      syndrome). Malignant forms were 21.7% of the total, including pheochromocytomas
      (n = 3), cortical carcinomas (n = 6), and metastases (n = 4). On CT, malignant
      masses were larger (8.4+/-0.9 cm) than benign ones (5.7+/-0.3 cm) (P < 0.0001)
      and the mass size was strictly related to malignancy (P < 0.03). CT did not offer
      other diagnostic criteria for malignancy, except irregular margins and regional
      lymph node enlargement, which were more frequently (P < 0.0001) found in
      malignant forms. 131I-MIBG scintigraphy showed tracer uptake in all
      pheochromocytomas, both benign and malignant. By contrast, on 131I-NC
      scintigraphy, cortical malignancies never accumulated the radiotracer, whereas
      uptake was observed in all cases of solid cortical benign adenomas. Patients with
      cortical carcinomas showed plasma sex steroids above the normal range,
      pheochromocytomas were asymptomatic in 15% of cases, and almost half of the
      patients with Cushing's syndrome did not show clinical features of the disease
      (pre-Cushing's syndrome). CONCLUSIONS: Adrenal macrotumors frequently show
      endocrine activity and the medulla seems to be involved more than the cortex.
      Pheochromocytomas and cortisol-secreting adenomas are sometimes asymptomatic.
      Malignancy is often found in macromasses and, at least for the cortical forms,
      size of the tumor on CT, 131I-NC uptake on scintigraphy, and determination of
      levels of sex steroids seem to be useful criteria for predicting the nature of
      the mass.

PMID- 9609628
TI  - Urologist-acquired renal access for percutaneous renal surgery.
AB  - OBJECTIVES: In most endourology programs an interventional radiologist is
      employed to acquire renal access for percutaneous renal surgery. Over the last 13
      years the senior endourologist at Oregon Health Sciences University has acquired
      access without employing a radiologist. We report our experience with urologist
      acquired renal access for percutaneous renal surgery in 522 cases. METHODS: We
      reviewed the records of all patients at our hospital who underwent percutaneous
      renal surgery between August 1983 and December 1996 with renal access being
      obtained in the operating room by a urologist. RESULTS: Four hundred fifty-six
      patients underwent 522 procedures. Indications for percutaneous renal surgery
      were renal and proximal ureteral calculi (n = 516), retained ureteral stent (n =
      3), and intrarenal collecting system tumor (n = 3). We were successful in gaining
      access to 513 of 522 kidneys (98.3%). Access was obtained via a subcostal
      approach in 344 procedures, over the 12th rib in 152 procedures, over the 11th
      rib in 15 procedures, and transabdominally in 2 procedures. Sixty-five patients
      (12.7%) required a second or multiple sites to facilitate complete removal of
      calculi. Our overall complication rate was 15.3%. Blood transfusion was required
      in 5.4% of the cases, ileus developed in 1.9%, pneumothorax in 1.1%,
      intraoperative hydrothorax in 1.1%, postoperative pleural effusion requiring
      aspiration in 0.9%, and septic shock in 0.9%. Our overall success rate for stone
      removal was 94.5%. CONCLUSIONS: In our experience, the urologist is able to
      safely and effectively obtain percutaneous access to the collecting system for
      percutaneous renal surgery as a one-stage procedure without the aid of
      interventional radiologists.

PMID- 9609629
TI  - Efficacy of multimodality therapy in advanced renal cell carcinoma.
AB  - OBJECTIVES: The integration of systemic biologic response modifier (BRM) therapy
      and surgery to treat metastatic renal cell carcinoma (RCC) is an evolving
      approach. The purpose of this study was to evaluate the efficacy of this form of
      multimodality therapy in patients with metastatic RCC. METHODS: Between 1988 and
      1996, 14 patients at our institution underwent initial BRM therapy followed by
      surgical resection of primary and metastatic RCC lesions. Patient records were
      reviewed to determine the response to BRM therapy, progression-free survival
      rate, and overall survival rate. The mean follow-up for the entire group was 43.5
      months. RESULTS: After BRM therapy, 9 patients manifested an objective response
      and 5 patients had stable disease. All patients were then rendered disease-free
      by surgical excision of residual or recurrent metastatic lesions and the primary
      tumor. The cancer-specific survival rate at 3 years was 81.5%. Currently, 7
      patients are alive and disease-free (mean follow-up 41.4 months), 3 patients are
      alive with recurrent disease (mean survival 48.3 months), 3 patients died of
      metastatic disease (mean survival 27.9 months), and 1 patient died of an
      unrelated cause 54.4 months after therapy. CONCLUSIONS: The results of this study
      suggest that adjunctive surgery after BRM therapy can extend the survival of
      selected patients with metastatic RCC. Aggressive surgical resection of stable or
      responding lesions after BRM therapy should be considered in the management of
      these patients.

PMID- 9609630
TI  - Altered expression of bladder mast cell growth factor receptor (c-kit) in
      interstitial cystitis.
AB  - OBJECTIVES: To investigate the presence of mast cell growth factor receptors (c
      kit) on bladder mast cells in interstitial cystitis (IC), a bladder condition
      occurring primarily in women. IC is characterized by pain, urgency, frequency,
      and mucosal microhemorrhages discernible with cystoscopy under general
      anesthesia. One of the prevailing theories to explain IC pathophysiology is the
      increased number of bladder mast cells, many of which are activated in at least a
      subgroup of IC patients. Stem cell factor (SCF), also known as c-kit ligand, is
      now recognized as the key molecule responsible for mast cell proliferation and is
      known to exert its action through specific surface receptors. METHODS: Bladder
      specimens from patients with IC, identified by the criteria established by the
      National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and
      control patients were obtained during diagnostic cystoscopy and were immediately
      fixed in 4% paraformaldehyde. They were then examined by immunohistochemistry for
      the unique proteolytic mast cell enzyme tryptase or the presence of c-kit, or
      both. RESULTS: Bladders of IC patients contained a higher number of mast cells
      than control patients. However, mast cells in IC patients expressed fewer c-kit
      on their surface than those in control patients. These results could be explained
      if the c-kit were occupied by endogenous SCF or were downregulated, possibly by
      internalization after ligand-receptor interactions, making them inaccessible to
      immunocytochemical detection. CONCLUSIONS: Bladder mastocytosis and/or activation
      of mast cells, in at least a subpopulation of IC patients, may be explained by
      increased stimulation of mast cells by SCF. These results could be explained
      either by a mutation leading to constitutive activation of c-kit or
      overproduction of c-kit ligand leading to bladder mast cell proliferation in IC.

PMID- 9609631
TI  - Static cytometry and neural networks in the discrimination of lower urinary
      system lesions.
AB  - OBJECTIVES: To investigate the potential of morphometry and artificial
      intelligence tools for the discrimination of benign and malignant lower urinary
      system lesions. METHODS: The study group included 50 cases of lithiasis, 61 cases
      of inflammation, 99 cases of benign prostatic hyperplasia, 5 cases of in situ
      carcinoma, 71 cases of grade I transitional cell carcinoma of the bladder (TCCB),
      and 184 cases of grade II and grade III TCCB. Images of voided urine smears
      stained by the Giemsa technique were analyzed by a custom image analysis system.
      The analysis gave a data set of features from 45,452 cells. A learning vector
      quantizer (LVQ)-type neural network (NN) was used to discriminate benign from
      malignant cells on the basis of the extracted morphometric and textural features.
      The data from 13,636 randomly selected cells were used as a training set and the
      data from the remaining 31,816 cells made up the test set. Similarly, in an
      attempt to discriminate at the patient level, 30% of the cases randomly selected
      were used to train an LVQ NN and the remaining 329 cases were used for the test.
      RESULTS: The application of the LVQ NN enabled the correct classification of
      95.42% of the benign cells and 86.75% of the malignant cells, giving an overall
      accuracy rate of 90.63%. At the patient level, the LVQ NN enabled the correct
      classification of 100% of benign cases and 95.6% of malignant cases, giving an
      overall accuracy rate of 97.57%. CONCLUSIONS: NNs combined with image analysis
      offer useful information in the discrimination of benign and malignant cells and
      lesions of the lower urinary system.

PMID- 9609632
TI  - Prospective pathologic analysis of female cystectomy specimens: risk factors for
      orthotopic diversion in women.
AB  - OBJECTIVES: To prospectively evaluate our previously established pathologic risk
      factors in women undergoing cystectomy for bladder cancer and to determine if
      these criteria identify appropriate female candidates for orthotopic diversion.
      METHODS: Prospective pathologic evaluation was performed on 71 consecutive female
      cystectomy specimens removed for primary transitional cell carcinoma of the
      bladder. The histologic grade, pathologic stage, presence of carcinoma in situ,
      number, and location of tumors were determined. In addition, final pathologic
      analysis of the bladder neck and proximal urethra was performed and compared with
      the intraoperative frozen-section analysis of the distal margin (proximal
      urethra). RESULTS: Tumor at the bladder neck and proximal urethra was seen in 14
      (19%) and 5 (7%) cystectomy specimens, respectively. Bladder neck tumor
      involvement was found to be the most significant risk factor for tumor involving
      the urethra (P <0.001). All patients with urethral tumors demonstrated
      concomitant bladder neck tumors. However, more than 60% of patients with bladder
      neck tumors had a normal (tumor-free) proximal urethra. Furthermore, no patient
      with a normal bladder neck demonstrated tumor involvement of the urethra.
      Intraoperative frozen-section analysis of the distal surgical margin was
      performed on 47 patients: 45 without evidence of tumor and 2 patients with
      urethral tumor involvement. In all cases, the intraoperative frozen-section
      analysis was correctly confirmed by final permanent section. CONCLUSIONS: We
      prospectively demonstrate that bladder neck tumor involvement is a significant
      risk factor for urethral tumor involvement in women. However, despite bladder
      neck tumor involvement, a number of women undergoing cystectomy for bladder
      cancer have a normal urethra and may be candidates for orthotopic diversion.
      Furthermore, our data demonstrate that intraoperative frozen-section analysis of
      the distal surgical margin accurately and reliably evaluates the proximal urethra
      and currently determines which patients undergo orthotopic diversion at our
      institution.

PMID- 9609633
TI  - Utility of the Bard BTA test in detecting upper urinary tract transitional cell
      carcinoma.
AB  - OBJECTIVES: The Bard BTA test has been shown in early studies to be useful in
      diagnosing transitional cell carcinoma (TCC) of the bladder. However, the utility
      of this test has not been evaluated for TCC of the upper urinary tract. We
      therefore evaluated the clinical utility of the BTA test for upper urinary TCC.
      METHODS: We tested 71 specimens from the ureter and/or renal pelvis in 22
      patients with a history or clinical suspicion for TCC and 9 patients with benign
      disorders. RESULTS: When compared to cytologic diagnoses, BTA had a sensitivity
      of 65%, a specificity of 40% (when correlated with clinical history), a false
      positive rate of 33%, and a false-negative rate of 62%. The test had a positive
      predictive value of 83% and a negative predictive value of 32%. CONCLUSIONS: The
      BTA does not have any clinical value in detecting upper urinary tract TCC.

PMID- 9609634
TI  - Preservation of putative continence nerves during radical retropubic
      prostatectomy leads to more rapid return of urinary continence.
AB  - OBJECTIVES: Urinary incontinence is a significant complication of radical pelvic
      surgery. A better understanding of the neuroanatomy of the rhabdosphincter has
      led to the modification of the radical retropubic prostatectomy to optimize the
      recovery of postoperative urinary control. METHODS: Mock radical retropubic
      prostatectomy was performed on fresh cadavers to determine which surgical
      maneuvers could injure what may be the continence nerves. To assess the clinical
      significance of modifying the radical retropubic prostatectomy based on these
      anatomic studies, a contemporary series of 60 consecutive patients who underwent
      radical retropubic prostatectomy with continence nerve preservation was compared
      with a control group of 38 consecutive patients who had a standard anatomic
      radical retropubic prostatectomy. RESULTS: At the level of the prostatic apex,
      both the pelvic and pudendal nerves gave intrapelvic branches that bilaterally
      coursed to the external urinary sphincter to enter at the 5 and 7 o'clock
      positions. The mock radical prostatectomy revealed that the nerves to the
      external urinary sphincter were most prone to injury when a right angle clamp was
      used to develop a plane between the posterior rhabdosphincter and anterior rectum
      and if the urethral anastomotic sutures were placed at the 5 and 7 o'clock
      positions. In addition, blunt dissection of the tips of the seminal vesicles
      injured the inferior hypogastric plexus. Modifications to preserve the continence
      nerves were incorporated in the anatomic radical prostatectomy. Although overall
      continence rates were similar for the two groups (98.3% for continence nerve
      preserving radical prostatectomy versus 92. 1% for standard prostatectomy),
      continence nerve preservation decreased the time to achieve continence.
      CONCLUSIONS: During radical retropubic prostatectomy, surgical maneuvers that
      avoid injury to the continence nerves resulted in the more rapid return of
      urinary control.

PMID- 9609635
TI  - Significance of familial history of prostate cancer to traditional prognostic
      variables, genetic biomarkers, and recurrence after radical prostatectomy.
AB  - OBJECTIVES: Prostate cancer (PCa) has a familial predisposition imparting an
      increased risk of developing the disease in those with a family history. The
      pathologic characteristics are similar to sporadic cases; however, the disease
      free survival rates of hereditary PCa have recently been disputed, with one major
      study suggesting that familial cases have higher recurrence rates. Our study
      seeks to support or refute this association and to evaluate the genetic
      biomarkers p53, bcl-2, Ki-67, and neovascularity between familial and sporadic
      disease. METHODS: We retrospectively reviewed data of 573 patients who underwent
      radical prostatectomy over an 11-year period. Of these, 474 patients had known
      family history data. Univariable statistical analysis using the Pearson chi
      square test and Kaplan-Meier disease-free survival analysis was performed to
      identify any correlation between the tested variables and family history. Smaller
      subsets of this cohort that had available archival material for
      immunohistochemical staining and family history data were analyzed in a similar
      manner. RESULTS: The preoperative variables (prostate-specific antigen, prostatic
      acid phosphatase, clinical stage, highest biopsy Gleason sum, and glandular
      differentiation) and postoperative variables (stage, highest Gleason sum, and
      glandular differentiation) did not correlate with family history. Kaplan-Meier
      disease-free survival analysis revealed no differences between sporadic and
      familial cases. The analysis of p53, bcl-2, Ki-67, and angiogenesis revealed that
      only increasing p53 expression and positive family history of PCa approached
      significance (P = 0.057). CONCLUSIONS: Prognostic variables routinely used in PCa
      and selected genetic biomarker immunostaining abnormalities are not significantly
      different in men with and without a family history of PCa. Disease-free survival
      after radical prostatectomy is also unaffected by family history.

PMID- 9609636
TI  - Radiolabeled monoclonal antibody indium 111-labeled CYT-356 localizes
      extraprostatic recurrent carcinoma after prostatectomy.
AB  - OBJECTIVES: The sites of recurrent carcinoma of the prostate were localized with
      radiolabeled monoclonal antibody, and these sites were correlated with the
      response of patients treated with pelvic radiation after prostatectomy. METHODS:
      Radionuclide scans were performed with indium 111-labeled CYT-356, a monoclonal
      antibody that binds to prostate epithelial cells, in 48 men diagnosed with
      recurrent carcinoma detected by prostate-specific antigen (PSA) screening after
      radical retropubic prostatectomy. RESULTS: In 48 patients with recurrent
      carcinoma detected by PSA screening following radical retropubic prostatectomy,
      73% had monoclonal antibody activity beyond the prostatic fossa, and only 3
      patients (6%) had activity in the prostatic fossa alone; 65% had monoclonal
      antibody activity in pelvic lymph nodes despite the fact that lymph node
      dissections were pathologically negative at the time of prostatectomy in 90% of
      the patients; and 23% of patients had monoclonal antibody activity in abdominal
      and extrapelvic retroperitoneal nodes. Of 48 patients, 13 underwent external beam
      radiation therapy after monoclonal antibody scans. Six patients had scans showing
      activity beyond the field of radiation, and radiation therapy failed in 4 of
      these patients. Seven patients had scans with no activity beyond the field of
      radiation therapy, and radiation therapy failed in only 2 of these patients.
      CONCLUSIONS: The scans frequently show monoclonal antibody uptake in pelvic,
      abdominal, and extrapelvic retroperitoneal sites beyond the region of limited
      obturator node dissections and may account for the understaging and subsequent
      failure of radical prostatectomy in some patients. The monoclonal antibody scan
      seems to be a good predictor of which patients will respond to radiation therapy
      after radical prostatectomy, but because these patients often have nodal activity
      beyond the radiated field, this initial response may not be curative.

PMID- 9609637
TI  - Age-related prostate cancer metastases.
AB  - OBJECTIVES: Metastatic prostate cancer results in significant patient morbidity,
      health care expenditure, and ultimately in mortality. We sought to identify
      patient and treatment factors predictive of distant metastases in patients
      completing external beam radiotherapy. METHODS: Five hundred sixty-seven patients
      completing external beam radiotherapy at Fox Chase Cancer Center, Philadelphia,
      Pennsylvania between March 1987 and November 1994 for Stage T1 to T3 tumors were
      analyzed. Distant metastases were detected by radionuclide bone scans. Estimates
      of rates for distant metastases as a first failure were conducted using
      cumulative incidence methods and predictors of failure were analyzed univariately
      and multivariately. RESULTS: The median follow-up was 46 months. On univariate
      analysis, the following were statistically significant predictors of distant
      metastases at 5 years: patient age greater than 65 years, pretreatment prostate
      specific antigen (PSA) level, advanced stage, lower radiation dose, and Gleason
      score 7 to 10. Multivariate testing confirmed that age greater than 65 years,
      high pretreatment PSA level, lower radiation dose, and advanced stage were
      significant independent predictors of distant metastases. CONCLUSIONS: Men over
      the age of 65 years are more likely to experience distant failure than are
      younger men. The discovery of age-related differences in patterns of failure has
      significant therapeutic implications with regard to patient selection, trial
      design, and adjuvant therapy recommendations. Furthermore, age-related
      differences in failure may influence comparison of outcome data for radiotherapy
      series, which tend to have older patients, to surgical reports that usually
      include significantly younger men.

PMID- 9609638
TI  - Late effects after radiotherapy for prostate cancer in a randomized dose-response
      study: results of a self-assessment questionnaire.
AB  - OBJECTIVES: To evaluate the late effects more than 2 years after radiotherapy
      using a patient-reported questionnaire in patients with prostate cancer enrolled
      in a randomized dose-response study comparing 70 Gy (conventional) and 78 Gy
      (conformal) radiotherapy (RT). METHODS: The first 112 patients in the study were
      sent questionnaires to evaluate late bladder, rectal, and sexual function. There
      were 101 evaluable responses, with 50 in the conventional (Conven-RT) arm and 51
      in the conformal (3DCRT) arm. RESULTS: The overall rate of persistent
      incontinence was 29%, with 36% reporting urgency-related and 8% stress-related
      incontinence at some time after radiation. Use of a urinary protective device was
      required in 2%. The majority noticed leakage less than once per day (52%). In
      comparing the Conven-RT group with the 3DCRT group, similar incontinence rates
      were seen. However, fewer of those who received 3DCRT reported daily leakage of
      urine (33% versus 63%, P = 0.044). The majority (78%) of patients experienced no
      or mild change in bowel function after RT. Urgency of bowel movements (BMs) was
      of concern for 27% of patients; however, 90% reported their BMs were controlled
      without accidents, and 1% were taking antidiarrheal medications once a week or
      daily. The Conven-RT group had more moderate or major changes in bowel function
      than the 3DCRT group (34% versus 10%), more frequent BMs (47% versus 27%), and
      more urgent BMs (37% versus 18%) (P < or = 0.040 for all three comparisons).
      Hematochezia was uncommon, occurring once a week in 7% and daily in 4% of
      patients. Before RT, 80% of patients were potent, with erections adequate for
      intercourse at least a few times over the prior year. After RT, potency was
      decreased to 51%, with erections adequate for intercourse at least a few times
      since the completion of RT. CONCLUSIONS: The overall rates of significant
      complications were extremely low. Although 30% reported incontinence, relatively
      few patients (2%) required pads. This rate compares favorably with the 31% of
      patients requiring protection after radical prostatectomy reported previously.
      Despite the higher treatment doses in the 3DCRT arm, slightly fewer long-term
      bowel side effects were noted. These data indicate that 78 Gy may safely be
      delivered using the conformal RT boost treatment technique described.

PMID- 9609639
TI  - Impact of postprostatectomy prostate-specific antigen nadir on outcomes following
      salvage radiotherapy.
AB  - OBJECTIVES: To evaluate the relationship between the postprostatectomy prostate
      specific antigen (PSA) nadir and the outcome of patients treated with salvage
      radiotherapy. METHODS: Seventy-eight patients received definitive external beam
      radiation for recurrence following radical prostatectomy (RP). The PSA nadir was
      undetectable in 41 patients (less than 0.05 ng/mL). All patients received salvage
      radiotherapy (median dose 66 Gy) for a median of 19 months (range 2 to 149)
      following prostatectomy. The median follow-up time was 25 months (range 1 to 59)
      from the date of completion of radiation. RESULTS: Among patients having an
      undetectable or detectable postoperative PSA, 78% and 68% were free of disease,
      respectively, at the last follow-up. At 3 years, the disease-free survival rates
      were 65% and 60%, respectively (P = 0.6). Overall, the disease-free survival rate
      at 3 years was 78% in patients with a PSA level 2 ng/mL or less at the time of
      radiotherapy compared to 31% with a PSA greater than 2 ng/mL (P < 0.0001).
      CONCLUSIONS: Many patients who never achieve an undetectable postprostatectomy
      PSA level may still be salvaged with therapeutic radiotherapy. The best predictor
      of a favorable outcome is a low (2 ng/mL or less) PSA level at the time of
      radiation.

PMID- 9609640
TI  - Saw palmetto (Serenoa repens) in men with lower urinary tract symptoms: effects
      on urodynamic parameters and voiding symptoms.
AB  - OBJECTIVES: To assess the effects of saw palmetto on voiding symptoms and
      urodynamic parameters in men with lower urinary tract symptoms (LUTS) presumed
      secondary to benign prostatic hyperplasia (BPH). METHODS: Fifty men with
      previously untreated LUTS and a minimum International Prostate Symptom Score
      (IPSS) of 10 or greater were treated with a commercially available form of saw
      palmetto (160 mg twice per day) for 6 months. The initial evaluation included
      measurement of peak urinary flow rate, postvoid residual urine volume, pressure
      flow study, and serum prostate-specific antigen (PSA) level. Patients completed
      an IPSS, serum PSA was determined, and flow rate was measured every 2 months
      during the course of the study. A urodynamic evaluation was repeated at the
      completion of the 6-month trial. RESULTS: The mean IPSS (+/-SD) improved from
      19.5+/-5.5 to 12.5+/-7.0 (P <0.001) among the 46 men who completed the study.
      Significant improvement in the symptom score was noted after treatment with saw
      palmetto for 2 months. An improvement in symptom score of 50% or greater after
      treatment with saw palmetto for 2, 4, and 6 months was noted in 21% (10 of 48),
      30% (14 of 47), and 46% (21 of 46) of patients, respectively. There was no
      significant change in peak urinary flow rate, postvoid residual urine volume, or
      detrusor pressure at peak flow among patients completing the study. No
      significant change in mean serum PSA level was noted. CONCLUSIONS: Saw palmetto
      is a well-tolerated agent that may significantly improve lower urinary tract
      symptoms in men with BPH. However, we were unable to demonstrate any significant
      improvement in objective measures of bladder outlet obstruction. Placebo
      controlled trials of saw palmetto are needed to evaluate the true effectiveness
      of this compound.

PMID- 9609641
TI  - Transurethral microwave thermotherapy for management of benign prostatic
      hyperplasia: a single-institution experience.
AB  - OBJECTIVES: This is the first and largest single institution retrospective study
      in the United States to examine the effects of transurethral microwave
      thermotherapy (TUMT) for the treatment of benign prostatic hyperplasia (BPH).
      METHODS: From September 1996 to June 1997, 78 men with moderate to severe
      symptomatic BPH were treated with the Prostatron at our institution. Patient age
      ranged from 52 to 85 years. Prostate volume ranged from 23 to 110 cc, and mean
      total energy applied during the treatment was 156.17 kJ. Patients were re
      evaluated at 3 months and were asked to answer a questionnaire regarding their
      opinion about the treatment. RESULTS: At 3 months there was a significant
      decrease in mean symptom score from 19.6 to 11.2 (P <0.0001). Mean peak flow rate
      increased from 8.5 to 12.8 mLs (P <0.0001). Mean postvoid residual urine
      decreased from 56.8 to 22.0 mL (P <0.0001). We did not observe any severe
      complications. Unlike prior studies, we removed the Foley catheter, and patients
      performed clean intermittent catheterization (CIC) when necessary. There was no
      significant differences in subjective and objective parameters between these
      patients and those who did not need CIC. Patient opinion about the treatment was
      not affected by CIC. About two thirds (67.2%) of the patients in the study group
      were satisfied with the results of treatment, and 60.3% would undergo the same
      procedure again. CONCLUSIONS: TUMT of the prostate is an effective, safe, and
      acceptable form of treatment for patients with BPH. Longer follow-up is needed to
      examine the durability of TUMT treatment.

PMID- 9609642
TI  - Outcome of vaportrode transurethral vaporization of the prostate using pressure
      flow urodynamic criteria.
AB  - OBJECTIVES: To use pressure-flow urodynamic parameters to evaluate the outcome of
      patients with benign prostatic hyperplasia (BPH) who were treated with
      transurethral vaporization of the prostate (TUVP) using the Vaportrode. METHODS:
      Forty consecutive patients (mean age 71.7 years) undergoing TUVP for treatment of
      symptomatic obstructive BPH or urinary retention were evaluated preoperatively
      and postoperatively with American Urological Association (AUA) Symptom Score,
      uroflowmetry, and pressure-flow multichannel urodynamic studies. RESULTS: Twenty
      nine patients were voiding preoperatively. Eleven patients presented with urinary
      retention and were analyzed separately. At 3-month mean follow-up, the AUA
      Symptom Score decreased from 20.7 to 7.2 (n = 26). Peak uroflow rate (Qmax)
      increased from 8.2 to 15.5 mL/s (n = 27), whereas detrusor pressure at maximal
      flow (Pdet) decreased from 95.0 to 44.7 cm H2O (n = 24), indicating relief of
      obstruction. Postvoid residual urine volume decreased from 181.8 to 37.3 mL (n =
      27). At 1-year mean follow-up, the AUA Symptom Score was 5.6 (n = 15) and Qmax
      was 14.3 mL/s (n = 19). The overall complication rate was 17.5% and included
      meatal stenosis (n = 1), bulbar urethral stricture (n = 1), refractory detrusor
      hyperreflexia (n = 1), dystrophic bladder neck calcification (n = 1), prostatic
      synechial formation requiring revision (n = 2), and residual prostatic tissue
      requiring revision (n = 1). CONCLUSIONS: This study provides objective evidence
      that TUVP is effective in providing prompt relief of bladder outlet obstruction
      with durable improvement in symptoms and flow rate with no acute morbidity.
      Accordingly, TUVP should continue to be considered as a minimally invasive
      surgical alternative to transurethral resection of the prostate.

PMID- 9609644
TI  - Childhood nocturnal enuresis in The Netherlands.
AB  - OBJECTIVES: To assess the prevalence of nocturnal enuresis in school children
      aged 5 to 15 years, and to investigate the association of bedwetting with
      ethnicity, the educational level of the parents, and the type of education
      (mainstream or special) received by the child. METHODS: Data were obtained for
      5360 children in mainstream education and 2571 children in special education. The
      data were weighted to calculate estimates representative of the Dutch population.
      Nocturnal enuresis was examined in children 5 or 6 years of age who wet their bed
      at least twice in the 4 weeks previous to questioning, and in children 7 years of
      age and older who did so at least once in the previous 4 weeks. RESULTS: The
      prevalence of nocturnal enuresis was 6%; 15% in the 5 to 6-year-age group and 1%
      in the 13 to 15-year age group. Marked enuresis (at least twice a week) was
      reported in 4%. Nocturnal enuresis was more common in Turkish/Moroccan (14%) than
      in Dutch children (6%). The educational level of the parents was not
      significantly related to nocturnal enuresis. Children in special education more
      frequently reported nocturnal enuresis than children in mainstream education (14%
      and 6%, respectively). This was especially true for children in schools for the
      mentally retarded as compared to children in mainstream education ?odds ratio
      [OR] in boys 3.21 (99% confidence interval [CI] 2.26 to 4.55) and OR in girls
      4.25 [99% CI 2.61 to 6.92]?. CONCLUSIONS: Nocturnal enuresis occurs most
      frequently among mentally retarded children. Children attending special education
      schools for reasons other than mental retardation are also at a higher risk of
      experiencing nocturnal enuresis than children attending mainstream education
      schools. Nocturnal enuresis is more prevalent in Turkish/Moroccan children than
      in Dutch children.

PMID- 9609643
TI  - Inconclusive clinical and ultrasound evaluation of the scrotum: impact of
      magnetic resonance imaging on patient management and cost.
AB  - OBJECTIVES: To determine the diagnostic utility and net cost of magnetic
      resonance imaging (MRI) in the management of clinically and sonographically
      inconclusive scrotal lesions. METHODS: A multicenter retrospective review
      identified 34 patients diagnosed with scrotal MRI following inconclusive clinical
      and ultrasound (US) evaluation. Final diagnoses were based on surgery (n = 18) or
      clinical and US follow-up (n = 16). Final diagnoses of 29 testicular lesions were
      as follows: orchitis (n = 11), infarct (n = 6), neoplasm (n = 6), rupture (n =
      3), torsion (n = 2), and radiation fibrosis (n = 1). Final diagnoses of five
      extratesticular lesions were as follows: epididymitis (n = 2), epididymal abscess
      (n = 2), and neoplasm (n = 1). Management plans prior to and following MRI
      findings were formulated by a general urologist and a urologic oncologist. The
      costs of the pre-MRI and post-MRI management plans were estimated using the
      Medicare reimbursement schedule. RESULTS: The leading US diagnosis was correct
      for 10 of 34 patients (29%) and the leading MRI diagnosis was correct for 31 of
      34 patients (91%). MRI improved the management plan of the general urologist and
      urologic oncologist in 19 patients (56%) and 17 patients (50%), respectively. MRI
      worsened the management plan of both clinicians in 1 patient. Management was
      unchanged in all other patients. The overall net cost savings were $543 to $730
      per patient for the urologic oncologist and the general urologist, respectively,
      and $3833 per patient originally scheduled for surgery. CONCLUSIONS: Use of MRI
      after inconclusive clinical and US evaluation of scrotal lesions may improve
      management, decrease the number of surgical procedures, and result in net cost
      savings.

PMID- 9609645
TI  - Placement of a bladder neck purse-string cuff for the management of incontinence
      in children with myelodysplasia.
AB  - OBJECTIVES: Numerous surgical procedures have been developed in an attempt to
      increase bladder compliance and/or outlet resistance for the treatment of
      intractable incontinence in children with neurogenic lower urinary tract
      dysfunction. We report our experience with the development of a biocompatable
      purse-string cuff to increase outlet resistance by providing circumferential
      compression at the bladder neck. METHODS: A total of 12 children (6 boys, 6
      girls) with myelodysplasia and persistent incontinence despite clean intermittent
      catheterization (CIC) and pharmacotherapy underwent urodynamic testing and
      cystoscopy that revealed neurogenic bladders with concomitant intrinsic sphincter
      deficiency. Through an anterior approach, the bladder neck was mobilized and
      wrapped with 5-mm polytetrafluoroethylene tubing. Five-millimeter woven polyester
      tape was then placed circumferentially within the polytetrafluoroethylene tubing
      lumen, purse-stringed under tension with a silicone tubing shod to appose the
      mucosa of the bladder neck, and secured under such tension with a surgical clip.
      Ten of the 12 patients underwent concomitant augmentation cystoplasty. RESULTS:
      Nine of 12 children (age range at time of operation 2.5 to 16 years) are
      continent on CIC in follow-up ranging from 6 months to 12 years. Four cuffs had
      to be surgically removed postoperatively. Two were removed secondary to
      inadvertent transvaginal placement. Two other cuffs were removed for infection.
      One child with persistent postoperative incontinence had the cuff retightened
      through a minor surgical procedure and has remained dry. Annual renal ultrasound
      examinations reveal stabilization of upper urinary tracts throughout the follow
      up period in all but 1 patient. Postoperative urodynamic studies reveal increased
      bladder capacity, decreased intravesical pressures, and increased leak point
      pressures. CONCLUSIONS: The purse-string bladder neck cuff in combination with
      augmentation cystoplasty, when warranted, provides excellent, durable continence
      rates in children with myelodysplasia and neurogenic bladders. Attributes of the
      cuff are its relative low cost, ease of construction, unchanged angle of the
      bladder neck making catheterization easy, and potential adjustability in patients
      with persistent incontinence.

PMID- 9609646
TI  - Use of a sponge stopper for placement of urethrovesical anastomotic sutures after
      radical prostatectomy or enterocystoplasty.
AB  - Vesicourethral anastomosis during radical retropubic prostatectomy or
      enterocystoplasty is often difficult because of poor visualization and collapse
      of the urethral stump. We have attempted to use a sponge stopper to facilitate
      urethral suture placement for vesicourethral anastomosis. The technique for use
      of a sponge stopper is described.

PMID- 9609647
TI  - Genitourinary tuberculosis.

PMID- 9609648
TI  - Obstructive uropathy due to sliding inguinal hernia.

PMID- 9609649
TI  - Epithelioid leiomyoma of the bladder: an unusual cause of voiding symptoms.
AB  - Epithelioid leiomyoma of the bladder is a rare benign neoplasm. A 63-year-old
      woman with a 2-year history of frequency and urgency was found to have a bladder
      mass on intravenous urography and subsequent cystoscopy. The mass was removed
      endoscopically. The patient's symptoms resolved.

PMID- 9609650
TI  - Fine needle aspiration biopsy of the penis: transitional cell carcinoma of the
      urinary bladder with mucinous differentiation.
AB  - We report a case of transitional cell carcinoma of the urinary bladder metastatic
      to the penis. The diagnosis was established by fine needle aspiration biopsy
      (FNAB). Malignant cells showed mucinous differentiation. Ancillary studies
      carried out in the FNA material as well as in the primary bladder carcinoma
      suggested transitional cell carcinoma with mucinous differentiation. FNAB proved
      to be effective in diagnosing a secondary neoplasm to the penis. Mucoid
      differentiation of urothelial cells can be seen in FNAB specimens and might pose
      a problem in differential diagnosis.

PMID- 9609651
TI  - Seminoma with isolated central nervous system relapse, and salvage with
      craniospinal irradiation.
AB  - We report a case of a patient with isolated central nervous system relapse of
      classical seminoma, refractory to intrathecal and systemic chemotherapy, but
      successfully salvaged with craniospinal axis irradiation. A 44-year-old man with
      bulky Stage II classic seminoma obtained complete remission with four cycles of
      cisplatin etoposide combination chemotherapy, but relapsed with lumbar vertebral
      metastases with epidural spinal cord compression 5 months after completion of
      primary treatment. He underwent laminectomy, local radiotherapy, and salvage
      chemotherapy. Two months later he developed cranial nerve palsies, and magnetic
      resonance imaging confirmed leptomeningeal disease. After brain radiotherapy,
      systemic and intrathecal chemotherapies were begun but tumor recurred around the
      cauda equina, producing paraparesis. The patient received salvage craniospinal
      irradiation, with resolution of paraparesis and cranial nerve palsies. Thirty
      months after completion of craniospinal radiotherapy, he remains in complete
      remission. We suggest consideration of craniospinal axis irradiation as salvage
      therapy in patients with isolated central nervous system relapse of seminoma.

PMID- 9609652
TI  - Association of human papillomavirus type 11 with carcinoma of the penis.
AB  - Human papillomaviruses (HPVs) are epithelium-tropic viruses associated with
      several cutaneous, epithelial, and mucosal lesions. The oncogenic potential
      varies considerably among the more than 70 different genotypes so far identified.
      HPV 6 and 11 are generally found in benign genital condilomata or laryngeal
      papillomas, but they have been sporadically associated with genital malignancies.
      Polymerase chain reaction (PCR) primed by degenerated consensus oligonucleotides
      (from a late region of the HPV genome) allows one to amplify a broad spectrum of
      HPV, whereas the amplification with specific primers is restricted to a limited
      number of HPVs. Therefore, the restriction fragment length polymorphism assay
      permits one to identify the HPV type present in the PCR product. We report a case
      of an invasive verrucous carcinoma of the penis associated with HPV 11, a type
      previously considered noncarcinogenic.

PMID- 9609653
TI  - Renal medullary carcinoma in patients with sickle cell trait.
AB  - Renal medullary carcinoma has recently been described as an aggressive neoplasm
      affecting young African Americans with sickle cell disease or sickle cell trait.
      We report the presentation, treatment, and outcome in 3 patients with renal
      medullary carcinoma along with a description of the unsuccessful treatment
      attempts. A brief discussion and review of the literature is included.

PMID- 9609654
TI  - Testicular effects of vasectomy in rats: an ultrastructural and
      immunohistochemical study.
AB  - OBJECTIVES: The correlation between infertility and morphofunctional alterations
      following vasal occlusion is not clearly understood. Although a correlation has
      been found between the expression of a high titer of antisperm antibodies and the
      status of infertility, the relationship between the immunoglobulin (Ig)
      depositions in the testis and ultrastructural alterations of the peritubular
      structures has not been clearly established. The objective of this study is to
      explain the etiopathogenesis of diffuse and focal testicular lesions caused by
      vasal obstruction. METHODS: Unilateral vasectomy was performed on adult male
      rats. Ultrastructural changes of testicular tissues and immunostaining affinity
      of peritubular structures with anti-actin, anti-vimentin, anti-laminin, and anti
      immunoglobulin G (anti-IgG) antibodies were analyzed. RESULTS: In an
      ultrastructural study, vasectomized animals presented abundant collagen fibril
      accumulation in the peritubular area. In testis with intense IgG antibodies,
      staining revealed weak immunostaining of peritubular myoid cells with anti-actin
      antibodies, but intense immunostaining with anti-vimentin antibodies. The tubules
      of rats with no IgG deposition on peritubular structures revealed intense
      immunostaining with anti-actin antibodies but scant immunostaining with anti
      vimentin antibodies. Anti-laminin deposits decreased severely in most of the
      tubules demonstrating intense IgG deposition. CONCLUSIONS: Our findings suggest
      that spermatogenesis deteriorates more severely in testes with dense IgG
      deposition. The sclerosis of the lamina propria in cases with vasal occlusion is
      secondary to alterations in the peritubular myoid cells. With the progressive
      changes that occur in the peritubular myoid cells or differentiation of the
      peritubular myoid cells that acquire active cell characteristics, collagen
      accumulation adjacent to these cells increases markedly. The alterations of the
      peritubular myoid cells reported here may be caused by alterations in basement
      membrane structures.

PMID- 9609656
TI  - Overactive bladder.

PMID- 9609655
TI  - P53, bcl-2, and Bax expression in renal cell carcinoma.
AB  - OBJECTIVES: Renal cell carcinomas often show a high degree of resistance to
      chemotherapy and radiation despite expressing normal function of the protein p53.
      The loss of control of apoptosis may also contribute to progression and
      resistance to treatment modalities and can be attributed to an interaction
      between p53 and the apoptotic regulators bcl-2 and Bax. To determine whether the
      expression of p53, bcl-2, or Bax could be correlated with outcome, we analyzed
      the expression pattern of these proteins in renal cell tumor samples. METHODS: We
      examined 28 patients with clear cell renal cell carcinomas along with 7 patients
      with papillary renal cell carcinomas and 4 with renal oncocytomas. All renal cell
      carcinomas were clinically localized Stage pT2 with tumor size ranging from 4.0
      to 10.3 cm (mean 6.23). Immunohistochemistry was performed on all samples and
      correlated with markers of outcome, including tumor grade, metastasis,
      recurrence, and overall survival rate. RESULTS: In all clear cell tumors, the
      detection level of p53 expression was below the sensitivity of the assay,
      consistent with the reported infrequent incidence of p53 mutations in renal cell
      cancers. bcl-2 expression showed a significant correlation (P = 0.018) with
      higher tumor grade but could not be significantly correlated with other
      parameters examined including tumor recurrence, metastasis, or survival rate. The
      expression of Bax could similarly be correlated with higher tumor grade but with
      none of the other parameters. CONCLUSIONS: At the present time, the combination
      of both tumor grade and stage represents the best prognostic markers available.
      Adjunctive use of bcl-2 and Bax staining currently plays a minimal role in
      helping to further stratify patients at high risk for disease progression or
      recurrence.

PMID- 9609657
TI  - Evidence for close contact between recombination nodules and the central element
      of the synaptonemal complex.
AB  - During the first part of meiosis, homologous chromosomes pair and undergo genetic
      recombination. Two meiotic structures are involved in these processes: the
      synaptonemal complex (SC) is essential for synapsis of the chromosomes, and the
      recombination nodules (RNs) represent the sites for recombination. In the present
      investigation we have used conventional electron microscopy to study the
      association between the SCs and the RNs in the beetle Blaps cribrosa. This
      experimental material was chosen because the spermatocytes in B. cribrosa display
      both exceptionally well-defined SCs and distinct RNs. We find that the RNs are
      drop shaped, located on top of the SC and oriented in parallel with the ribbon
      like SC. The most striking observation is that the RNs coalesce with the top
      layer of the central element of the SC. The RNs are also connected via fibres to
      the lateral elements of the SC. These and other structural observations suggest
      that the RNs could influence the synapsis of homologous chromosomes by affecting
      both early and late steps in the assembly of the SCs.

PMID- 9609658
TI  - DNA methylation of the extraembryonic tissues: an in situ study on human
      metaphase chromosomes.
AB  - DNA methylation level and pattern of human metaphase chromosomes from
      extraembryonic tissues (chorionic villi and placental fibroblasts) were analysed
      in situ. The DNA methylation global level of these tissues was studied by
      comparing them with the one observed in fetal fibroblasts and adult lymphocytes.
      In order to assess the tissue specificity and significance of the observed
      differences, chromosomal preparations were then treated in parallel. They were
      first stained with distamycin A/DAPI and pictured, then treated with
      immunofluorescent staining using monoclonal antibodies raised against 5
      methylcytosine. Compared with metaphases from lymphocytes or placental and fetal
      fibroblasts, distamycin-A/DAPI stained metaphases and constitutive
      heterochromatic regions with very similar intensities. In contrast, in chorionic
      villi, the immunofluorescent intensities revealing the presence of 5
      methylcytosine was much duller than in the other tissues. In addition, in both
      chorionic villi and placental fibroblasts, large differences were observed
      between various chromosome structures within individual metaphases. In
      particular, the secondary constriction of chromosome 9, the distal segment of
      chromosome Y and the short arms of acrocentric chromosomes exhibited a much lower
      staining than the one observed for the secondary constrictions of chromosome 1
      and 16 of the same metaphases. Because all these structures are known to be
      deeply methylated in other somatic tissues, this suggests that in extraembryonic
      tissues DNA methylation level remained hypomethylated and the pattern is under
      precise control.

PMID- 9609659
TI  - A 169-base pair tandem repeat DNA marker for subtelomeric heterochromatin and
      chromosomal rearrangements in aphids of the Myzus persicae group.
AB  - Numerous copies of a 169-base pair DNA sequence (Myzus persicae group repeat;
      MpR) occur at subtelomeric locations on all chromosomes of three members of the
      Myzus persicae species group (Myzus persicae, M. antirrhinii, M. certus). MpR
      occurs in large tandem arrays at both ends of all autosomes of the standard 2n =
      12 karyotype, and near one end of the X chromosome (the end opposite to the
      nucleolar organizer) and is estimated to make up about 5% of the genome (a total
      of about 200000 copies). Locations of MpR were compared in various karyotypes to
      determine the likely nature of the rearrangements (fusions, dissociations,
      translocations) that are found in this species group which, like other Hemiptera,
      has holocentric chromosomes that are devoid of morphological markers. Aphid
      clones heterozygous for autosome dissociations do not have any detectable MpR at
      'new' chromosome ends, indicating that this sequence is not involved in 'capping'
      of chromosomes. However, a clone with a de novo autosome fusion had an
      interstitial block of MpR marking the point of fusion, and clones heterozygous
      for an autosomal 1,3 translocation had MpR from autosome 1 translocated to a new
      site on autosome 3. The isolation from M. antirrhinii of the telomeric repeat
      TTAGG, which is found in several insect groups, is also reported.

PMID- 9609660
TI  - Orientation of the 'stretched' univalent X chromosome during the unequal first
      meiotic division in male aphids.
AB  - In situ hybridization was used to label the ends of the X chromosomes of two
      aphid species, Myzus persicae and Amphorophora tuberculata, in order to study the
      peculiar behaviour and orientation of the univalent X in aphid spermatogenesis.
      Anaphase I begins with the long axis of the X chromosome at right angles to the
      spindle and its two chromatids closely associated, but as the division proceeds
      the chromatids separate along most of their lengths, retaining only a midway
      connection as the X chromosome becomes stretched on the spindle. Both ends of one
      chromatid move towards one pole, while both ends of the other chromatid move
      towards the other pole. However, the midway connection is retained and the whole
      X chromosome eventually passes into one daughter cell. This form of X chromosome
      behaviour is common to all aphids and therefore presumably dates back to the
      Permian. It is independent of the type of meiosis, which in aphids can be
      'normal' (reductional first division) or 'inverted' (reductional second
      division).

PMID- 9609661
TI  - Molecular cytogenetic characterization of Thinopyrum and wheat-Thinopyrum
      translocated chromosomes in a wheat-Thinopyrum amphiploid.
AB  - The wheat-Thinopyrum amphiploid 'Agrotriticum # 3425' (AT 3425), which is highly
      resistant to Cephalosporium stripe, was identified to carry seven pairs of
      Thinopyrum chromosomes, three pairs of wheat-Thinopyrum translocated chromosomes
      and 18 pairs of wheat chromosomes. Fluorescence genomic in situ hybridization
      (FGISH), C-banding, sequential C-banding and FGISH, and denaturing polyacrylamide
      gel electrophoresis (SDS-PAGE) were used to characterize and identify the
      chromosomes. The Thinopyrum chromosomes in AT 3425 were designated as T1 through
      T7 based on their C-banding patterns. The FGISH and C-banding patterns of mitotic
      chromosomes in AT 3425 and meiotic chromosomes in the hybrid between AT 3425 and
      wheat cultivar 'Chinese Spring' (CS) revealed that wheat chromosomes 1D, 2B and
      3D were involved in the three wheat-Thinopyrum chromosome translocations
      designated as (W-T)1, (W-T)2, and (W-T)3 respectively. The analysis of high
      molecular-weight glutenin subunits in single seeds of AT 3425 confirmed the
      involvement of wheat chromosome 1D in the translocation (W-T)1. The designations
      1DSx1DL-1TL, 2BSx2BL-2TL and 3DSx3DL-3TL were suggested for the wheat-Thinopyrum
      translocated chromosomes (W-T)1, (W-T)2 and (W-T)3 in AT 3425 respectively.

PMID- 9609662
TI  - Tandem duplication of nucleolus organizer region (NOR) in the Japanese macaque,
      Macaca fuscata fuscata.
AB  - During exploration of chromosome polymorphisms in Japanese macaques, a
      heteromorphic polymorphism was found in a population in the Zigokudani monkey
      park. The population consisted of three troops (social units). Of 36 monkeys
      examined, five females showed heterozygotic 'marker' chromosome (chromosome 9).
      The polymorphism was a tandem duplication of the nucleolus organizer region (NOR)
      of the short arm of chromosome 9, which was found for the first time in the genus
      Macaca. FISH and fibre-FISH using human 18S rDNA and sequential silver nitrate
      staining revealed that the duplicated region included a part of the euchromatic
      satellite and the stalk and that the euchromatic block (intercalary satellite)
      divided the NOR into two parts (distal and proximal). Furthermore, it showed that
      the distal region possessed much more rDNA than the proximal region, and that the
      duplications might have been introduced via a mechanism of gene amplification
      (inverted duplications associated with over-replication and recombination
      events). As the tandem duplication was observed sporadically in four maternal
      pedigrees in two troops and the mothers of the variants all had normal
      chromosomes, the variation might have been introduced from another population's
      gene pool by a solitary male immigrant.

PMID- 9609663
TI  - Localization of the human membrane-type 2 matrix metalloproteinase gene (MMP15)
      to 16q12.1 near DNA elements that are part of centromeric and non-centromeric
      heterochromatin of 11 human chromosomes.
AB  - We have localized a second gene for membrane-type matrix metalloproteinases, MT2
      MMP, to chromosome 16q12 by in situ hybridization. FISH experiments using a
      genomic PAC clone containing the MT2-MMP gene resulted in an unusual
      hybridization pattern detecting centromeric and non-centromeric heterochromatin
      regions or its flanking sequences in 11 human chromosomes in addition to the MT2
      MMP locus on chromosome 16q12. The detailed analysis of this hybridization
      pattern using molecular cytogenetic methods together with the specific
      hybridization of the MT2-MMP cDNA allowed a refined mapping of the gene to
      16q12.1, directly adjacent to the 16q heterochromatin. Our findings may give some
      insights into the evolution of the MMP gene family.

PMID- 9609664
TI  - Molecular cytogenetic analysis of heterochromatin in the chromosomes of tilapia,
      Oreochromis niloticus (Teleostei: Cichlidae).
AB  - The structure of the heterochromatic bands in mitotic chromosomes of the
      important tropical aquaculture species of tilapia, Oreochromis niloticus, was
      investigated by the combination of the C-banding technique, chromosomal digestion
      with two restriction endonucleases and fluorescence in situ hybridization (FISH)
      of two satellite DNAs (SATA and SATB). The tilapia chromosomes presented
      heterochromatic bands in the centromeres and in the short arms of almost all
      chromosomes that were differentially digested by the restriction endonucleases
      HaeIII and EcoRI. FISH of SATA showed that this satellite sequence is distributed
      in the centromeric region of all chromosomes of tilapia. FISH also revealed an
      intense hybridization signal for SATB in only one chromosome pair, but less
      intense signals were also present in several other pairs. The digestion of
      tilapia chromosomes by HaeIII and EcoRI was positively correlated with the
      position of SATA and SATB in chromosomes as revealed by FISH. The results
      obtained may be useful in future molecular and genetic studies of tilapias.

PMID- 9609665
TI  - Microdissected bovine X chromosome segment delineates homoeologous chromosomal
      regions in sheep, goat and buffalo.
AB  - The terminal part of the long arm of the bovine X chromosome (bands Xq41-q43) was
      microdissected. The DNA thus obtained was PCR amplified, labelled and used as
      painting probe on cattle, sheep, goat and buffalo chromosomes. In cattle, as
      expected, distinct hybridization signals were observed on bands Xq41-q43. In
      sheep and goat, the painting signals were observed on the proximal part of the
      long arm of the X chromosome, adjacent to the centromere (Xp12-q12). In buffalo,
      however, the terminal part of the X chromosome involving bands q44-q47 was
      painted. The findings contribute towards developing a better understanding of the
      comparative organization of the X chromosome in the four bovidae species.
      Proposed models of evolutionary rearrangements within the X chromosome of the
      four species are examined in light of the results obtained.

PMID- 9609666
TI  - Molecular-cytogenetic characterization of the Vicia faba genome--heterochromatin
      differentiation, replication patterns and sequence localization.
AB  - A comprehensive survey of the molecular-cytogenetic features of the Vicia faba
      chromosome complement (2n = 12) is given. It includes previous as well as new
      original data. Various Giemsa, restriction endonuclease and fluorochrome banding
      patterns, azacytidine-mediated segment extension, replication patterns, lateral
      A/T asymmetry and sequence localization data for tandemly arranged simple
      sequence repeats, dispersed repeats and coding sequences as well as histone
      acetylation patterns are considered. This allows not only to distinguish and
      characterize telomeres, subtelomeres, centromeres and the NOR, but also the
      structure of the 5S rRNA gene loci and two main types of interstitial
      heterochromatin. Additionally, it offers physical landmarks within euchromatic
      areas. Thus, the field bean genome, exemplified by the reconstructed karyotype
      ACB, belongs to the cytogenetically best investigated plant genomes.

PMID- 9609667
TI  - Mapping of five members of the cyclin gene family on chicken chromosomes by FISH.

PMID- 9609668
TI  - Simultaneous detection of p53 nuclear protein and chromosome aberrations on
      sections from formalin-fixed, paraffin-embedded breast cancer tissue.

PMID- 9609670
TI  - Chromosome Webwatch.

PMID- 9609669
TI  - Localization of a repetitive DNA sequence to the primary constrictions of maize
      pachytene chromosomes.

PMID- 9609671
TI  - Porcine Agouti gene map position SSC 17q21.

PMID- 9609672
TI  - Altered cerebral energy utilization in late life depression.
AB  - BACKGROUND: Global and regional changes in cerebral energy utilization are
      reported to characterize late life depression. METHODS: Twenty seven subjects
      with late life depression (9 prior to starting medication, 18 after starting) and
      27 matched controls were evaluated with cordance, a quantitative EEG measure that
      reflects cerebral energy utilization. RESULTS: Global and focal (anterior and
      centrotemporal) differences were present in theta-band cordance between
      unmedicated depressed and control subjects. Depressed subjects receiving
      treatment had cordance patterns similar to controls. CONCLUSIONS: The presence of
      both diffuse and focal disturbances in energy utilization prior to initiating
      treatment indicates that cordance detects altered cerebral physiology in
      depressed patients, and that this measure may also be sensitive to treatment
      interventions.

PMID- 9609673
TI  - Predictors of recurrence in affective disorder. A case register study.
AB  - BACKGROUND: The risk of recurrence in affective disorder is affected by socio
      demographic variables such as gender, age at onset and marital status and by
      illness related factors as the length of previous episodes and the total duration
      of the illness. The present study investigated how the effect of these variables
      changed with the progression of the illness. METHOD: Using survival analysis, the
      risk of recurrence was estimated in a case register study including all hospital
      admissions with primary affective disorder in Denmark during 1971-1993. RESULTS:
      Totally, 20350 first admission patients had been discharged with a diagnosis of
      affective disorder, depressive or manic/circular type. Initially in the course of
      the illness, bipolar patients had a substantial greater risk of recurrence
      compared with unipolar patients. At this time, gender, age and marital status
      together with the total duration of the illness predicted the risk of recurrence
      in both unipolar and bipolar illness. Some variables had different predictive
      effect in the two types of illness. Later, especially the duration of the
      previous illness predicted the risk of recurrence. CONCLUSION: It seems as
      initially in the course of affective disorder socio-demographic variables such as
      gender, age at onset and marital status act as risk factors for further
      recurrence. Later, however, the illness itself seem to follow its own rhythm
      regardless of prior predictors. LIMITATION: The data relate to re-admissions
      rather than recurrence and the findings may be due to decreasing sample sizes
      during the course of illness. CLINICAL RELEVANCE: The study underscores the
      importance of the illness process itself.

PMID- 9609674
TI  - Light treatment for nonseasonal depression: speed, efficacy, and combined
      treatment.
AB  - BACKGROUND: Using bright light for treating major depressive disorders which are
      not seasonal needs reassessment. METHODS: Clinical trials of light treatment for
      nonseasonal major depressive disorders were compared with selected trials of
      light treatment of winter depression and with antidepressant clinical drug
      trials. RESULTS: Light treatment of nonseasonal depression produces net benefits
      in the range of 12-35%, often within 1 week. CONCLUSIONS: Light's value for
      nonseasonal and seasonal depression are comparable. Light appears to produce
      faster antidepressant benefits than psychopharmacologic treatment. LIMITATIONS:
      Direct randomizing comparisons between light and medications for nonseasonal
      depression are not available. CLINICAL RELEVANCE: Bright light can be combined
      with standard therapies for treating nonseasonal depressions and appears
      synergistic.

PMID- 9609675
TI  - Olanzapine in treatment-resistant bipolar disorder.
AB  - BACKGROUND: We evaluated the response to olanzapine in 14 consecutive patients
      with bipolar I disorder who were inadequately responsive to standard psychotropic
      agents. METHODS: Fourteen patients with bipolar I disorder by DSM-IV criteria
      experiencing persistent affective symptoms inadequately responsive to at least
      one standard mood stabilizer were treated with open-label olanzapine by one of
      the authors. Response was assessed with the Clinical Global Impression Scale
      modified for use in bipolar disorder (CGI-BP). RESULTS: The 14 patients received
      olanzapine at a mean (SD dosage of 14.1+/-7.2 (range 5-30) mg/day for a mean+/-SD
      of 101.4+/-56.3 (range 30-217) days of treatment. Of the 14 patients, 8 (57%)
      displayed much or very much overall improvement in their illness. In general,
      olanzapine was well tolerated. The most common side effects were sedation,
      tremor, dry mouth, and appetite stimulation with weight gain. LIMITATIONS: Data
      were obtained nonblindly and without a randomized control group, and olanzapine
      was added to ongoing psychotropic regimens. CONCLUSION: Olanzapine may have
      antimanic and mood-stabilizing effects in some patients with bipolar disorder,
      and is generally well tolerated. Controlled studies of olanzapine in bipolar
      disorder appear warranted.

PMID- 9609676
TI  - A neuropsychological study of panic disorder: negative findings.
AB  - BACKGROUND: Gray (1982) proposed that the septo-hippocampal system, which plays
      an important role in learning and memory, may partially mediate anxiety. Thus,
      patients with anxiety disorders may manifest neurocognitive performance deficits.
      We hypothesized that patients with panic disorder would demonstrate learning and
      memory deficits relative to normal comparison subjects. METHOD: Comprehensive
      neuropsychological batteries were administered to 69 panic disorder subjects and
      19 normal volunteers. RESULTS: There were no significant group differences in any
      neuropsychological performance domain including learning, memory, attention,
      visuospatial functioning, and psychomotor speed. Multiple regression conducted to
      evaluate the contribution of clinical symptoms to neuropsychological impairment
      within the panic disorder sample revealed that anxiety severity did not affect
      neuropsychological test performance. LIMITATIONS: Most patients had mild or
      moderate, rather than severe, panic disorder. CONCLUSION: Neuropsychological
      dysfunction was not associated with panic disorder.

PMID- 9609677
TI  - Patterns of mood variation during antidepressant treatment.
AB  - Previous findings showed that, in a subgroup of patients administered
      heterogeneous antidepressant treatments, perceived mood levels during a major
      depressive episode fluctuate with day to day changes which follow cyclical
      patterns (termed "minicycles"). We investigated the predictability of infradian
      mood fluctuations during acute depressive episodes in patients standardly
      medicated with fluvoxamine. We applied time series analysis, by means of
      autocorrelation techniques, to time lagged serial recordings of perceived mood
      levels of 20 inpatients (13 Major Depression Recurrent, and 7 Bipolar Depressive
      Disorders). 5/20 patients exhibited predictable cyclical patterns in their
      perceived symptomathology, 8/20 exhibited an uneven, sawtooth pattern of
      progressive amelioration, and 7/20 showed an erratic pattern of unpredictable day
      to-day variations. We confirmed the existence and the predictability of cyclical
      mood patterns in a subgroup of patients. The absence of a linear improvement in
      perceived mood did not worsen the final response to antidepressant therapy.

PMID- 9609678
TI  - The SSRI antidepressants: exploring their "other" possible properties.
AB  - BACKGROUND: Anecdotal reports suggest that the SSRIs may have important
      properties in addition to their antidepressant effects, possibly modifying
      mediating variables that dispose to and maintain depression. This preliminary
      study seeks to identify any such potential variables. METHODS: Fifty three
      subjects who had reported substantial general benefit to their clinician after
      treatment with an SSRI were requested to retrospectively rate change across a
      range of constructs assessed by questionnaire. RESULTS: Differential effects were
      identified. Irritability, trait depression, worry and neuroticism scores showed
      the most marked improvement, with cognitive style components also showing
      significant positive change. Equally importantly, there was no evidence of a
      positive response bias across all constructs. CONCLUSION: We suggest that the
      SSRIs may act as "antiworry" agents and reduce irritability, neuroticism and
      dysfunctional attributions. LIMITATIONS: Our study was retrospective and relied
      on self-report by volunteer patients who had been previously depressed. The study
      design cannot exclude the possibility that improvement reported on a number of
      measures may have been due to the amelioration of residual depression. CLINICAL
      RELEVANCE: The SSRIs, recognised as having antidepressant and anti-obsessional
      properties, may also have the capacity to lower irritability, worrying and
      neuroticism. This capacity could be useful per se but may, in addition, reduce
      the occurrence and duration of depressive episodes, particularly by reducing
      "anxious worrying".

PMID- 9609679
TI  - Seasonal affective disorder: report from India (latitude 26 degrees 45'N).
AB  - BACKGROUND: A number of studies have established the entity of seasonal affective
      disorder (SAD) and delineated the presence of atypical depressive features of
      carbohydrate craving, hyperphagia and hypersomnia. Most literature has emanated
      from research carried out in temperate climates, and only few reports are
      available from tropical countries, especially India. METHODS: Consecutive
      patients with recurrent mood disorder (who had at least 2 episodes of depression
      in the past) comprised the study sample. The diagnosis of mood disorder was made
      according to DSM-III-R criteria. The sample was divided into two groups -
      seasonal and non-seasonal according to the DSM-III-R criteria of seasonal
      pattern. The depressed patients were rated on SADD and HDRS, and manic patients
      on BRMRS. RESULTS: Eighteen of 93 patients fulfilled the criteria of seasonal
      pattern; 7 of these seasonal patients, and 25 of the non-seasonal patients were
      currently in depressive phase. Males dominated the sample in both the groups. The
      seasonal and non-seasonal groups as regards symptomatology, differed only on a
      few items - decreased libido on SADD, and suicidal ideation and helplessness on
      HDRS. Atypical vegetative features were not seen in any of the seasonal patients.
      CONCLUSIONS: SAD is seen at lower latitudes also, although atypical vegetative
      features are not a prominent part of the symptomatology. LIMITATIONS: The study
      sampled was obtained from a very select population, and thus does not indicate
      the prevalence of SAD in India. Secondly, the small sample size precludes any
      categorical comments of the symptomatology. Moreover, winter and summer
      depressives were considered as one group. CLINICAL RELEVANCE: Emphasising the
      presence of SAD in a tropical country where there is relatively less variation in
      daylight periods, this report forms a base for future studies. It also raises the
      question of the role of variations in daylight in the aetiology SAD.

PMID- 9609680
TI  - The relationship of suicide attempts, borderline personality traits, and major
      depressive disorder in a veteran outpatient population.
AB  - BACKGROUND: Suicide attempts have been associated to both Major Depression and
      Borderline Personality Disorder. This report hypothesized that there would be
      significant clinical differences between psychiatric outpatients with Major
      Depression, Major Depression with a history of a suicide attempt (but low
      Borderline traits) and Major Depression high levels of Borderline personality
      traits. METHODS: Male psychiatric outpatients who had Major Depression were
      divided into three groups: No suicide attempts and low Borderline traits
      (Depression), suicide and low Borderline traits (Suicide) and high Borderline
      traits (Borderline traits.) A screened control group was also used (Controls).
      Standardized measures of Axis I and Axis II variables were gathered by trained
      interviewers. RESULTS: "Suicide" had significantly higher levels of anxiety and
      depression than all other groups. "Borderline traits" had higher levels of
      pathological personality traits and familial Generalized Anxiety Disorder (GAD)
      than all other groups. CONCLUSIONS AND CLINICAL RELEVANCE: The Suicide group
      appears to identify a group that is more symptomatically severe in Axis I
      symptoms than other Major Depression groups. Different Major Depression groups
      may require different treatments. The association between Borderline and GAD
      warrants further research. LIMITATIONS: This study used male veterans in middle
      age. The usual cautions about generalizing findings to other demographic groups
      apply.

PMID- 9609681
TI  - Effects of lamotrigine on the 5-HT1A receptor function in healthy human males.
AB  - BACKGROUND: Lamotrigine, a new anticonvulsant, has recently been reported to be
      effective in treating patients with bipolar mania, depression, and
      schizoaffective disorder, suggesting that it is perhaps a mood stabilizer with
      antimanic and antidepressant properties. However, the mechanism of action
      underlying its efficacy in mood disorders is still unknown. METHODS: To explore
      the role of 5-HT1A receptors in the mechanism of action of lamotrigine, we
      measured the body temperature and plasma cortisol responses to a challenge with a
      selective 5-HT1A receptor agonist ipsapirone in ten healthy human males. Each
      subject received 0.3 mg/kg of ipsapirone hydrochloride tablets at time "0". Body
      temperature readings and blood samples for cortisol levels were obtained at 0,
      30, 60, 90, 120, 150, 180 min. The ipsapirone challenge tests were repeated after
      1 week treatment with lamotrigine (100 mg/day). RESULTS: Treatment with
      lamotrigine for 1 week did not significantly alter the hypothermic or cortisol
      responses to ipsapirone. LIMITATIONS: The limitations of this study included
      small sample size, low treatment dose, short treatment interval, and lack of
      placebo control. CONCLUSIONS: Our findings might suggest that 5-HT1A receptor
      function is not involved in the mechanism of action of lamotrigine in humans.
      Further placebo-controlled studies with a higher lamotrigine dose and a longer
      treatment interval in a larger number of subjects are needed to verify this.

PMID- 9609682
TI  - Functional expression of P-glycoprotein in the hepatic canalicular membrane of
      developing rats 

PMID- 9609683
TI  - Protein farnesyltransferase: structure and implications for substrate binding.
AB  - The rat protein farnesyltransferase crystal structure has been solved by multiple
      isomorphous replacement methods at a resolution of 2.75 A. The three-dimensional
      structure, together with recent data on the effects of several mutations, led us
      to propose a model for substrate binding which differs from the model presented
      by Park et al. based on their independent structure determination [Park, H. -W.,
      Boduluri, S. R., Moomaw, J. F., Casey, P. J., and Beese, L. S. (1997) Science
      275, 1800-1804]. Both farnesyl diphosphate and peptide substrates can be
      accommodated in the hydrophobic active-site barrel, with the sole charged residue
      inside the barrel, Arg202 of the beta-subunit, forming a salt bridge with the
      negatively charged carboxy terminus of peptide substrates. Our proposals are
      based in part on the observation of electron density in the active site which can
      be modeled as bound farnesyl diphosphate carried through the enzyme purification.
      In addition, our model explains in structural terms the results of mutational
      studies which have identified several residues critical for substrate specificity
      and catalysis.

PMID- 9609684
TI  - The structure of the monomeric porcine odorant binding protein sheds light on the
      domain swapping mechanism.
AB  - The X-ray structure of the porcine odorant binding protein (OBPp) was determined
      at 2.25 A resolution. This lipocalin is a monomer and is devoid of naturally
      occurring bound ligand, contrary to what was observed in the case of bovine OBP
      [Tegoni, M., et al. (1996) Nat. Struct. Biol. 3, 863-867; Bianchet, M. A., et al.
      (1996) Nat. Struct. Biol. 3, 934-939]. In this latter protein, a dimer without
      any disulfide bridges, domain swapping was found to occur between the beta- and
      alpha-domains. A single Gly (121) insertion was found in OBPp when it was
      compared to OBPb, which may prevent domain swapping from taking place. The
      presence of a disulfide bridge between the OBPp beta- and alpha-domains
      (cysteines 63 and 155) may lock the resulting fold in a nonswapped monomeric
      conformation. Comparisons with other OBPs indicate that the two cysteines
      involved in the OBPp disulfide bridge are conserved in the sequence, suggesting
      that OBPp may be considered a prototypic OBP fold, and not OBPb.

PMID- 9609685
TI  - Two high-resolution crystal structures of the recombinant N-lobe of human
      transferrin reveal a structural change implicated in iron release.
AB  - The N-lobe of human serum transferrin (hTF/2N) has been expressed in baby hamster
      kidney cells and crystallized in both orthorhombic (P212121) and tetragonal
      (P41212) space groups. Both crystal forms diffract to high resolution (1.6 and
      1.8 A, respectively) and have been solved by molecular replacement. Subsequent
      refinement resulted in final models for the structure of hTF/2N that had
      crystallographic R-factors of 18.1 and 19.7% for the two crystal forms,
      respectively; these models represent the highest-resolution transferrin
      structures determined to date. The hTF/2N polypeptide has a folding pattern
      similar to those of other transferrins, including the presence of a deep cleft
      that contains the metal-binding site. In contrast to other transferrins, both
      crystal forms of hTF/2N display disorder at the iron-binding site; model building
      suggests that this disorder consists of alternative conformations of the
      synergistically bound carbonate anion, the side chain for Arg-124, and several
      solvent molecules. Subsequent refinement revealed that conformation A has an
      occupancy of 0.63-0. 65 and corresponds to the structure of the iron-binding site
      found in other transferrins. The alternative conformation B has an occupancy of
      0.35-0.37; in this structure, the carbonate has rotated 30 degrees relative to
      the iron and the side chain for Arg-124 has moved to accommodate the new
      carbonate position. Several water molecules appear to stabilize the carbonate
      anion in the two conformations. These structures are consistent with the
      protonation of the carbonate and resulting partial removal of the anion from the
      metal; these events would occur prior to cleft opening and metal release.

PMID- 9609686
TI  - NMR solution structure of the 21 kDa chaperone protein DnaK substrate binding
      domain: a preview of chaperone-protein interaction.
AB  - The solution structure of the 21 kDa substrate-binding domain of the Escherichia
      coli Hsp70-chaperone protein DnaK (DnaK 386-561) has been determined to a
      precision of 1.00 A (backbone of the beta-domain) from 1075 experimental
      restraints obtained from multinuclear, multidimensional NMR experiments. The
      domain is observed to bind to its own C-terminus and offers a preview of the
      interaction of this chaperone with other proteins. The bound protein region is
      tightly held at a single amino acid position (a leucyl residue) that is buried in
      a deep pocket lined with conserved hydrophobic residues. A second hydrophobic
      binding site was identified using paramagnetically labeled peptides. It is
      located in a region close to the N-terminus of the domain and may constitute the
      allosteric region that links substrate-binding affinity with nucleotide binding
      in the Hsp70 chaperones.

PMID- 9609687
TI  - Human general transcription factor TFIIB: conformational variability and
      interaction with VP16 activation domain.
AB  - Human TFIIB, an essential factor in transcription of protein-coding genes by RNA
      polymerase II, consists of an amino-terminal zinc binding domain (TFIIBn)
      connected by a linker of about 60 residues to a carboxy-terminal core domain
      (TFIIBc). The TFIIB core domain has two internally repeated motifs, each
      comprising five alpha-helices arranged as in the cyclin box. Compared to the
      crystal structure of TFIIBc in complex with TBP and a TATA-containing
      oligonucleotide, the NMR-derived solution structure of free TFIIBc is more
      compact, with a different repeat-repeat orientation and a significantly shorter
      first helix in the second repeat. Analysis of backbone 15N relaxation parameters
      indicates the presence of relatively large amplitude, nanosecond time-scale
      motions in the TFIIBc interrepeat linker and structural fluctuations throughout
      the backbone. Interaction of TFIIBc with the acidic activation domain of VP16 or
      with TFIIBn induces 1H-15N chemical shift and line width changes concentrated in
      the first repeat, interrepeat linker and the first helix of the second repeat.
      These results suggest that TFIIB is somewhat pliable and that the conformation of
      the C-terminal core domain can be modulated by interaction with the N-terminal
      zinc binding domain. Furthermore, binding of the VP16 activation domain may
      promote TFIIBc conformations primed for binding to a TBP-DNA complex.

PMID- 9609688
TI  - Contribution of the beta subunit M2 segment to the ion-conducting pathway of the
      acetylcholine receptor.
AB  - We have applied the substituted-cysteine-accessibility method (SCAM) to the M2
      segment and the M1-M2 loop of the acetylcholine (ACh) receptor beta subunit. Each
      residue from beta P248 to beta D273 was mutated one at a time to Cys, and the
      mutant beta subunits were expressed together with wild-type alpha, beta, and
      delta subunits in Xenopus oocytes. For each of the mutants, the ACh-induced
      current was near wild-type. The accessibility of the substituted Cys was inferred
      from the irreversible inhibition or potentiation of ACh-induced current by
      methanethiosulfonate (MTS) derivatives added extracellularly. Inhibition by
      MTSethylammonium of beta G255C, in the narrow part of the channel, was mainly due
      to a reduction in the single-channel conductance. Conversely, potentiation by
      MTSethylammonium of beta V266C, in a wider part of the channel, was mainly due to
      an increase in channel open-time. Two substituted Cys at the intracellular end of
      M2 and three at the extracellular end were accessible to MTSethylammonium in the
      absence of ACh. Three additional Cys in the middle of M2 and three in the M1-M2
      loop were accessible in the presence of ACh. In the presence of ACh, the
      secondary structure of beta M2 is alpha-helical from beta G255 to beta V266 and
      extended from beta L268 to beta D273. The accessible residues in beta M2 are
      remarkably hydrophobic, while the accessible residues in the M1-M2 loop are
      charged. beta M2, like alpha M2, alpha M1, and beta M1, undergoes widespread
      structural changes concomitant with gating, but the gate itself is close to the
      intracellular end of the channel. Many aligned residues in the M2 segments of
      alpha and beta are not identically accessible, indicating that the two subunits
      contribute differently to the channel lining.

PMID- 9609689
TI  - Backbone and side chain dynamics of uncomplexed human adipocyte and muscle fatty
      acid-binding proteins.
AB  - Adipocyte lipid-binding protein (A-LBP) and muscle fatty acid-binding protein (M
      FABP) are members of a family of small ( approximately 15 kDa) cytosolic proteins
      that are involved in the metabolism of fatty acids and other lipid-soluble
      molecules. Although highly homologous (65%) and structurally very similar, A-LBP
      and M-FABP display distinct ligand binding characteristics. Since ligand binding
      may be influenced by intrinsic protein dynamical properties, we have
      characterized the backbone and side chain dynamics of uncomplexed (apo) human A
      LBP and M-FABP. Backbone dynamics were characterized by measurements of 15N T1
      and T2 values and ?1H?-15N NOEs. These data were analyzed using model-free
      spectral density functions and reduced spectral density mapping. The dynamics of
      methyl-containing side chains were charaterized by measurements of 2H T1 and
      T1rho relaxation times of 13C1H22H groups. The 2H relaxation data were analyzed
      using the model-free approach. For A-LBP, 15N relaxation data were obtained for
      111 residues and 2H relaxation data were obtained for 42 methyl groups. For M
      FABP, 15N relaxation data were obtained for 111 residues and 2H relaxation data
      were obtained for 53 methyl groups. The intrinsic flexibilities of these two
      proteins are compared, with particular emphasis placed on binding pocket
      residues. There are a number of distinct dynamical differences among
      corresponding residues between the two proteins. In particular, many residues
      display greater backbone picosecond to nanosecond and/or microsecond to
      millisecond time scale mobility in A-LBP relative to M-FABP, including F57, K58,
      and most residues in alpha-helix 2 (residues 28-35). Variations in the dynamics
      of this region may play a role in ligand selectivity. The side chains lining the
      fatty acid binding pocket display a wide range of motional restriction in both
      proteins. Side chains showing distinct dynamical differences between the two
      proteins include those of residues 20, 29, and 51. This information provides a
      necessary benchmark for determining dynamical changes induced by ligand binding
      and may ultimately lead to an enhanced understanding of ligand affinity and
      selectivity among fatty acid-binding proteins.

PMID- 9609691
TI  - A divalent metal site in the small subunit of the manganese-dependent
      ribonucleotide reductase of Corynebacterium ammoniagenes.
AB  - Based on its metallo-cofactor, the manganese-dependent ribonucleotide reductase
      (Mn-RRase) responsible for delivery of DNA precursors in the Mn-requiring Gram
      positive bacterium Corynebacterium (formerly Brevibacterium) ammoniagenes ATCC
      6872 is no longer considered as a simple analogue of the aerobic Fe-RRase of
      Escherichia coli but as the prototype of the class IV enzymes (1). Deliberate
      dissociation of the Mn-RRase holoenzyme and an improved sample preparation of the
      dimeric CA2 protein allowed further characterization of the inherent metallo
      cofactor by Q-band electron paramagnetic resonance (EPR) spectroscopy. At 40 K, a
      distinct hyperfine sextet (I = 5/2,55Mn) pattern with a weak zero-field splitting
      was detected in the CA2 protein prepared from manganese-sufficient cells
      displaying high RRase activity as expected. This Q-band Mn(II) signal was absent
      in the apo-CA2 protein obtained from manganese-depleted cells devoid of this
      enzymatic activity. The presence of a mixed valence manganese cluster in the C.
      ammoniagenes RRase is excluded since no complex multiline EPR signals were
      detected in the CA2 protein even at very low (8 K) temperature. The observed
      Mn(II) spectrum indicates a protein-bound manganese which was modified in the
      presence of 5.7 mM p-methoxyphenol, but is insensitive toward 10 mM EDTA. Thus,
      the manganese appeared to be either strictly bound or buried within a hydrophobic
      pocket of the CA2 protein, inaccessible for EDTA.

PMID- 9609690
TI  - A mutational analysis of binding interactions in an antigen-antibody protein
      protein complex.
AB  - Alanine scanning mutagenesis, double mutant cycles, and X-ray crystallography
      were used to characterize the interface between the anti-hen egg white lysozyme
      (HEL) antibody D1.3 and HEL. Twelve out of the 13 nonglycine contact residues on
      HEL, as determined by the high-resolution crystal structure of the D1.3-HEL
      complex, were individually truncated to alanine. Only four positions showed a
      DeltaDeltaG (DeltaGmutant - DeltaGwild-type) of greater than 1.0 kcal/mol, with
      HEL residue Gln121 proving the most critical for binding (DeltaDeltaG = 2.9
      kcal/mol). These residues form a contiguous patch at the periphery of the epitope
      recognized by D1.3. To understand how potentially disruptive mutations in the
      antigen are accommodated in the D1.3-HEL interface, we determined the crystal
      structure to 1.5 A resolution of the complex between D1.3 and HEL mutant Asp18 -
      > Ala. This mutation results in a DeltaDeltaG of only 0.3 kcal/mol, despite the
      loss of a hydrogen bond and seven van der Waals contacts to the Asp18 side chain.
      The crystal structure reveals that three additional water molecules are stably
      incorporated in the antigen-antibody interface at the site of the mutation. These
      waters help fill the cavity created by the mutation and form part of a rearranged
      solvent network linking the two proteins. To further dissect the energetics of
      specific interactions in the D1.3-HEL interface, double mutant cycles were
      carried out to measure the coupling of 14 amino acid pairs, 10 of which are in
      direct contact in the crystal structure. The highest coupling energies, 2.7 and
      2.0 kcal/mol, were measured between HEL residue Gln121 and D1.3 residues VLTrp92
      and VLTyr32, respectively. The interaction between Gln121 and VLTrp92 consists of
      three van der Waals contacts, while the interaction of Gln121 with VLTyr32 is
      mediated by a hydrogen bond. Surprisingly, however, most cycles between interface
      residues in direct contact in the crystal structure showed no significant
      coupling. In particular, a number of hydrogen-bonded residue pairs were found to
      make no net contribution to complex stabilization. We attribute these results to
      accessibility of the mutation sites to water, such that the mutated residues
      exchange their interaction with each other to interact with water. This implies
      that the strength of the protein-protein hydrogen bonds in these particular cases
      is comparable to that of the protein-water hydrogen bonds they replace. Thus, the
      simple fact that two residues are in direct contact in a protein-protein
      interface cannot be taken as evidence that there necessarily exists a productive
      interaction between them. Rather, the majority of such contacts may be
      energetically neutral, as in the D1.3-HEL complex.

PMID- 9609692
TI  - Adsorption of vitamin K-dependent blood coagulation proteins to spread
      phospholipid monolayers as determined from combined measurements of the surface
      pressure and surface protein concentration.
AB  - Spread phospholipid monolayers are particularly useful as model membranes in that
      changes in surface pressure (Deltapi) can be monitored in response to protein
      adsorption to the monolayer, thus providing a unique manner of assessing protein
      membrane contact. In the present study, spread monolayers below their collapse
      pressures have been utilized to evaluate Ca2+-specific adsorption of several
      vitamin K-dependent coagulation proteins to monolayers that contain negatively
      charged phospholipid. From combined measurements of Deltapi and Gamma (the
      surface excess protein concentration), values of dGamma/dpi have been evaluated
      for different proteins with varying lipid composition of the monolayers. Using
      mixed, liquid-expanded monolayers at equivalent initial surface pressures (pii)
      and which contain different amounts of phosphatidylserine, phosphatidylcholine,
      and phosphatidylethanolamine, the dGamma/dpi of bovine prothrombin was shown to
      decrease monotonically with increasing protein affinity for the monolayer. For
      example, KD values of 7, 20, and 60 nM produced dGamma/dpi values of 14, 17, and
      21 nmol m-1 mN-1, respectively. However, the trend in dGamma/dpi appears to
      originate from characteristics of the monolayer and not from those of the
      protein, since a much different adsorbate (i.e., a positively charged pyrene
      derivative) exhibited a similar trend in dGamma/dpi with monolayer composition.
      On the other hand, dGamma/dpi values of bovine prothrombin, human factor IX,
      human protein S, bovine protein C, and human protein C, determined using liquid
      expanded phosphatidylserine monolayers, were essentially equivalent. Therefore,
      the five vitamin K-dependent proteins that were examined were equivalent in terms
      of the manner in which the gamma-carboxyglutamic acid (Gla) domain of each
      protein perturbed the surface pressure. This study shows that Ca2+-specific
      membrane contact sites in the Gla domain of the five proteins tested are similar
      despite the naturally occurring differences in the normal Gla domain sequence of
      these proteins.

PMID- 9609693
TI  - Mutational and crystallographic analyses of interfacial residues in annexin V
      suggest direct interactions with phospholipid membrane components.
AB  - Annexin V belongs to a family of eukaryotic calcium-dependent membrane-binding
      proteins. The calcium-binding sites at the annexin-membrane interface have been
      investigated in some detail; however, little is known about the functional roles
      of highly conserved interfacial residues that do not coordinate calcium
      themselves. In the present study, the importance of tryptophan 185, and threonine
      or serine at positions 72, 144, 228, and 303, in rat annexin V is investigated by
      site-directed mutagenesis, X-ray crystallography, and functional assays. The high
      resolution crystal structures of the mutants show that the mutations do not cause
      structural perturbations of the annexin molecule itself or disappearance of bound
      calcium ions from calcium-binding sites. The assays indicate that relative to
      wild-type annexin V, loss of the methyl substituent at position 72 (Thr72-->Ser)
      has no effect while loss of the hydroxyl group (Thr72-->Ala or Thr72-->Lys)
      causes reduction of membrane binding. Multiple lysine substitutions (e.g.,
      Thr72,Ser144,Ser228,Ser303-->Lys) have a greater adverse effect than the single
      lysine mutation, suggesting that in annexin V the introduction of potentially
      favorable electrostatic interactions between the lysine side chains and the net
      negatively charged membrane surface is not sufficient to overcome the loss of the
      hydroxyl side chains. Replacement of the unique tryptophan, Trp185, by alanine
      similarly decreases membrane binding affinity. Taken together, the data suggest
      that the side chains mutated in this study contribute to phospholipid binding and
      participate directly in intermolecular contacts with phospholipid membrane
      components.

PMID- 9609694
TI  - Transport of long-chain native fatty acids across human erythrocyte ghost
      membranes.
AB  - Evidence from a number of laboratories suggests that membrane proteins may
      meditate the transport of physiologic fatty acids (FA) across cell membranes.
      However, actual transport of unbound free fatty acids (unbound FFA) from the
      aqueous phase on one side of a cell membrane to the aqueous phase on the other
      side has not been measured previously. In this study, we have used the
      fluorescent probe of unbound FFA, ADIFAB, to monitor the time course of FA
      movement from the outer to the inner aqueous compartments, and from the lipid
      membrane to the outer aqueous compartment of red cell ghosts. These two
      measurements, together with measurements of the lipid/aqueous partition
      coefficients, allowed the determination of the rate constants for binding (kon),
      flip-flop (kff), and dissociation (koff) for the transport of long-chain natural
      FA across red cell ghosts. Measurements done using palmitate, oleate, and
      linoleate at temperatures between 20 and 37 degreesC revealed that the overall
      transport times ranged from about 0.5 to more than 10 s, depending upon FA type
      and temperature. Analysis of these time courses yielded kff values between 0.3
      and 3.0 s-1, and these values were consistent with those obtained using ghosts
      containing pyranine to detect intracellular acidification by the translocating
      FA. The measured koff values ranged from about 0.3 to 5 s-1, while the rate of
      binding, for the ghost concentrations used in this study (>50 microM
      phospholipid), exceed both kff and koff. Thus, long-chain FA transport across red
      cell ghost membranes is rate-limited by a combination of flip-flop and
      dissociation rates. Binding of FA to ghost membranes was well described by
      simple, nonsaturable, aqueous/membrane partition, and that partition appears to
      be governed by the aqueous solubility of the FA. Transport rates did not reveal
      any evidence of saturation and were not affected by a variety of protein-specific
      reagents. These FA binding and transport characteristics are similar to those
      observed previously for lipid vesicles, although the rate constants are generally
      about 2-3 fold larger for ghosts as compared to the lipid vesicles. We suggest,
      therefore, that FA transport across red cell ghosts is reasonably well described
      by transport across the lipid phase of the membrane.

PMID- 9609695
TI  - Ligand-induced changes in periplasmic loops in the lactose permease of
      Escherichia coli.
AB  - N- and C-terminal halves of lactose permease, each with a single-Cys residue in a
      periplasmic loop, were coexpressed, and cross-linking was studied in the presence
      or absence of ligand. A Cys residue at position 36 between transmembrane helices
      I and II (loop I/II) forms a disulfide spontaneously with a Cys residue at
      position 253, 254, 255, or 256 in loop VII/VIII. Moreover, in the presence of o
      phenanthroline-copper, a Cys residue at position 42 in loop I/II forms a
      disulfide with a Cys residue at position 253, 254, 257, or 258 in loop VII/VIII.
      Changes in the rate of cross-linking are also observed in the presence of
      substrate, suggesting that ligand binding induces movement between loops I/II and
      VII/VIII such that positions 253-256 are brought closer to position 36 or 42,
      while positions 257 and 258 move away from position 42.

PMID- 9609696
TI  - Calcium is not required for 5-lipoxygenase activity at high phosphatidyl choline
      vesicle concentrations.
AB  - 5-Lipoxygenase (5-LO) catalyzes the formation of 5-hydroperoxy-eicosatetraenoic
      acid (5-HPETE) and leukotriene A4 (LTA4) from arachidonic acid. Following a rise
      in intracellular calcium, 5-LO translocates to a membrane where it reacts with
      arachidonic acid via an 18 kD protein (FLAP). In vitro studies using a vesicle
      system of phosphatidylcholine (PC) and purified 5-LO were conducted under varying
      concentrations of PC and calcium. At high PC concentrations, 5-LO partitioned
      onto the vesicle containing arachidonic acid, resulting in product formation in
      the absence of calcium. Addition of calcium increased the initial rate of the
      reaction with a small increase in product accumulation. Dilution experiments in
      the absence of calcium at high PC concentrations indicated that binding of 5-LO
      to the vesicles is rapidly reversible. In the presence of calcium, this binding
      is much more favorable than without calcium. Stimulation of 5-LO activity by
      dithiothreitol (DTT) was more pronounced at high PC concentrations than at low PC
      concentrations. The requirement for ATP for maximal activity was independent of
      vesicle concentration. Inhibitors that functioned in the conditions of low PC
      with calcium present also inhibited under high PC without calcium. In the
      presence of PC and calcium and without substrate, the enzyme was unstable and was
      rapidly and irreversibly inactivated. In high PC without calcium, the enzyme was
      much more stable but it was still subject to turnover-dependent inactivation.
      Fluorescence energy-transfer experiments confirmed the kinetic findings that 5-LO
      could bind to the vesicle in the absence of calcium. These results show that in
      the absence of calcium, 5-LO can reversibly bind to the vesicle containing
      arachidonic acid and produce the same amount of product by a similar mechanism as
      observed with low PC and calcium. Calcium likely causes a conformational change
      that increases the affinity of the enzyme for the vesicle, but it is not strictly
      required for enzymatic activity and has no effect on the function of the
      catalytic site.

PMID- 9609697
TI  - Tertiary structural changes in the cleft containing the ATP sensitive tryptophan
      and reactive thiol are consistent with pivoting of the myosin heavy chain at
      Gly699.
AB  - The conformation of myosin subfragment 1 (S1) in the vicinity of the ATP
      sensitive tryptophan (Trp510) and the highly reactive thiol (SH1), both residing
      in the "probe-binding" cleft at the junction of the catalytic and lever arm
      domains, was studied to ascertain its role in the mechanism of energy
      transduction and force generation. In glycerinated muscle fibers in rigor, a
      fluorescent probe linked to SH1 detects a strained probe-binding cleft
      conformation following a length transient by altering emission intensity without
      detectably rotating. In myosin S1 in solution, the optical activity of Trp510
      senses conformation change in the probe-binding cleft caused by substrate analog
      trapping of S1 in various structures attainable transiently during normal energy
      transduction. Also in S1 in solution, the induced optical activity of a
      fluorescein probe linked to SH1 shows sensitivity to changing probe-binding cleft
      conformation caused by nucleotide binding to the S1 active site. The changes in
      the optical activity of Trp510 and SH1 bound fluorescein in response to
      nucleotide or nucleotide analog binding are interpreted structurally using the S1
      crystallographic coordinates and aided by a model of energy transduction that
      pivots at Gly699 to change probe-binding cleft conformation and to displace the
      S1 lever arm as during force generation. The crystallographic structure of the
      probe-binding cleft in S1 resembles most the nucleotide bound conformation in the
      native protein. A different structure, generated by pivoting at Gly699, better
      resembles the native rigor conformation of the probe-binding cleft. Pivoting at
      Gly699 rotates probes at SH1 suggesting that length transients on fibers in rigor
      do not cause pivoting at Gly699 or reverse the power stroke.

PMID- 9609698
TI  - Binding of SH1-SH2-modified myosin subfragment-1 to actin.
AB  - Myosin subfragment-1 (S1) was labeled with NPM in the presence of ATP or with
      pPDM in the presence of ADP at 0 degreesC, conditions which favor linking of
      maleimide groups to both Cys-707 (SH1) and Cys-697 (SH2). Unmodified S1 was
      removed by sedimentation with a small amount of F-actin, and the modified protein
      in the supernatant thoroughly dialyzed. The myosin high-salt EDTA and calcium
      ATPase activities of the isolated modified S1 were close to zero, suggesting
      nearly complete modification of SH1 and SH2. The binding of control and these
      modified myosins to actin was measured at 100 mM ionic strength using a co
      sedimentation assay. In the presence of high MgATP concentration, control and NPM
      and pPDM-reacted S1 all bind weakly to actin, with binding constants K3 of 4.9,
      2.2, and 1.9 x 10(4) M-1, respectively. In the absence of MgATP, the binding
      constant K2 of pPDM-reacted S1 remains weak, 4.6 x 10(4) M-1,while that of NPM
      reacted and control S1 becomes strong, 4.7 and 31 x 10(6) M-1, respectively. The
      binding constant for ATP to acto-NPM-reacted-S1 is approximately 2 x 10(4) M-1.
      Our data suggest that the binding of NPM-S1 to F-actin, in contrast to that of
      pPDM-S1, is ATP sensitive and can be quite strong at very low ATP concentration.
      They also suggest that while simple alkylation of SH1 and SH2 may be sufficient
      to inhibit myosin's ability to hydrolyze ATP, actual covalent linkage of SH1 and
      SH2 may be necessary to inhibit the weakly to strongly binding conformational
      change.

PMID- 9609699
TI  - Structural interactions between horseradish peroxidase C and the substrate
      benzhydroxamic acid determined by X-ray crystallography.
AB  - The three-dimensional structure of recombinant horseradish peroxidase in complex
      with BHA (benzhydroxamic acid) is the first structure of a peroxidase-substrate
      complex demonstrating the existence of an aromatic binding pocket. The crystal
      structure of the peroxidase-substrate complex has been determined to 2.0 A
      resolution with a crystallographic R-factor of 0.176 (R-free = 0. 192). A well
      defined electron density for BHA is observed in the peroxidase active site, with
      a hydrophobic pocket surrounding the aromatic ring of the substrate. The
      hydrophobic pocket is provided by residues H42, F68, G69, A140, P141, and F179
      and heme C18, C18-methyl, and C20, with the shortest distance (3.7 A) found
      between heme C18-methyl and BHA C63. Very little structural rearrangement is seen
      in the heme crevice in response to substrate binding. F68 moves to form a lid on
      the hydrophobic pocket, and the distal water molecule moves 0.6 A toward the heme
      iron. The bound BHA molecule forms an extensive hydrogen bonding network with
      H42, R38, P139, and the distal water molecule 2.6 A above the heme iron. This
      remarkably good match in hydrogen bond requirements between the catalytic
      residues of HRPC and BHA makes the extended interaction between BHA and the
      distal heme crevice of HRPC possible. Indeed, the ability of BHA to bind to
      peroxidases, which lack a peripheral hydrophobic pocket, suggests that BHA is a
      general counterpart for the conserved hydrogen bond donors and acceptors of the
      distal catalytic site. The closest aromatic residue to BHA is F179, which we
      predict provides an important hydrophobic interaction with more typical
      peroxidase substrates.

PMID- 9609700
TI  - Chromium(III) modification of the first metal binding site of phosphoenolpyruvate
      carboxykinase.
AB  - Chicken liver phosphoenolpyruvate carboxykinase (PEPCK) is activated by Cr2+ as
      the sole activator under anaerobic conditions. PEPCK was modified with Cr3+,
      starting with either Cr2+ or Cr3+. Cr3+ has the distinct advantage of being a
      paramagnetic cation that could serve as a paramagnetic probe. Activators Mn2+,
      Mg2+, and Co2+ protect against Cr3+ incorporation. EPR, CD, and fluorescence
      studies indicate that Cr3+ was incorporated into the cation binding site of
      PEPCK. The water proton relaxation rate (PRR) and fluorescence binding studies
      showed that Cr3+(n1)-PEPCK forms enzyme-substrate complexes similar to those
      observed for the Mn2+(n1)-PEPCK complex (n1 represents the metal "enzyme binding
      site" as opposed to the metal "nucleotide binding site"). Cr3+(n1)-PEPCK requires
      an additional divalent cation for activity, an indication of two metal sites on
      PEPCK. Cr3+(n1)-PEPCK retains 15% residual activity as compared to unmodified
      PEPCK and demonstrates normal Michaelis-Menten kinetics. This is the first report
      of an active Cr3+-modified enzyme complex.

PMID- 9609701
TI  - The effect of boundary selection on the stability and folding of the third
      fibronectin type III domain from human tenascin.
AB  - Correct selection of domain boundaries is critical for structural analysis of
      single domains from multimodular proteins. Folding and stability studies of the
      third fibronectin type III domain from human tenascin (TNfn31-90) have shown that
      it is moderately stable (Delta G(D-N)(H2O) approximately 5 kcal mol-1) and folds
      with two-state kinetics. In an attempt to stabilize the protein, five domains
      were constructed with different combinations of extensions to the N- and C
      termini. Thermal denaturation studies show that a specific two amino acid (Gly
      Leu) extension at the C-terminus is primarily responsible for a significant
      increase in stability. The Delta Delta G(D-N)(H2O) of the Gly-Leu extension
      (TNfn3(1-92)) is 2.7 +/- 0.3 kcal mol-1. Refolding kinetics do not differ
      significantly, but unfolding is slowed 40-fold. Mutation of leucine 92 to alanine
      does not affect stability, indicating that the stability of the extension does
      not come from the packing of the leucine side chain. Hydrogen exchange data
      suggest that the extension adds new hydrogen bonds and strengthens existing
      hydrogen bonds in the C-terminal interaction with the A-B and E-F loops. Removal
      of a very small number of hydrogen bonds substantially increases the unfolding
      rate, a phenomenon which may be important in stress-relaxation of FNIII
      containing muscle proteins such as titin. These experiments demonstrate the
      importance of a small number of additional long-range interactions in the overall
      formation of a compact independently folding beta-sheet module.

PMID- 9609702
TI  - Spectroscopic characterization of recombinant pea cytosolic ascorbate peroxidase:
      similarities and differences with cytochrome c peroxidase.
AB  - Recombinant pea cytosolic ascorbate peroxidase (APX) has been characterized by
      resonance Raman (RR) and electronic absorption spectroscopies. The ferric and
      ferrous forms together with the complexes with fluoride and imidazole have been
      studied and compared with the corresponding spectra of cytochrome c peroxidase
      (CCP). Ferric APX at neutral pH is a mixture of 6- and 5-coordinate high-spin and
      6-c low-spin hemes, the latter two species being dominant. The results suggest
      that the low-spin form derives from a water/hydroxo ligand bound to the heme iron
      and not from a strong internal ligand as observed in CCP at alkaline pH. Two Fe
      Im stretching modes are identified, as in CCP, but the RR frequencies confirm a
      weaker His163-Asp208 hydrogen bond than in CCP, as suggested on the basis of the
      X-ray structure [Patterson, W. R., and Poulos, T. L. (1995) Biochemistry 34, 4331
      4341]. The data show that CCP and APX have markedly different orientations of the
      vinyl substituents on the heme chromophore resulting from different steric
      constraints exerted by the protein matrix.

PMID- 9609703
TI  - Early and late M intermediates in the bacteriorhodopsin photocycle: a solid-state
      NMR study.
AB  - To enforce vectorial proton transport in bacteriorhodopsin (bR), it is necessary
      that there be a change in molecular structure between deprotonation and
      reprotonation of the chromophore-i.e., there must be at least two different M
      intermediates in the functional photocycle. We present here the first detection
      of multiple M intermediates in native wild-type bacteriorhodopsin by solid-state
      NMR. Illumination of light-adapted [zeta-15N-Lys]-bR at low temperatures shifts
      the 15N signal of the retinal Schiff base (SB) downfield by about 150 ppm,
      indicating a deprotonated chromophore. In 0.3 M Gdn-HCl at pH 10.0, two different
      M states are obtained, depending on the temperature during illumination. The M
      state routinely prepared at the lower temperature, Mo, decays to the newly
      observed M state, Mn, and the N intermediate, as the temperature is increased.
      Both relax to bR568 at 0 degreesC. A unique reaction sequence is derived: bR568-
      >Mo-->(Mn+N)-->bR568. Mo and Mn have similar chemical shifts at [12-13C]ret, [14
      13C]ret, and [epsilon-13C]Lys216, indicating that Mn, like Mo, has a 13-cis and
      C=N anti chromophore. However, a small splitting in the [14-13C]ret signal of Mo
      reveals that it has at least two substates. The 7 ppm greater shielding of the SB
      nitrogen in Mn compared to Mo suggests an increase in basicity and/or hydrogen
      bonding. Probing the peptide backbone of the protein, via [1-13C]Val labeling,
      reveals a substantial structural change between Mo and Mn including the
      relaxation of perturbations at some sites and the development of new
      perturbations at other sites. The combination of the change in the protein
      structure and the increase in the pKa of the SB suggests that the demonstrated Mo
      ->Mn transition may function as the "reprotonation switch" required for vectorial
      proton transport.

PMID- 9609704
TI  - Kinetic studies on bovine cytochrome p45011 beta catalyzing successive reactions
      from deoxycorticosterone to aldosterone.
AB  - The reactions for the synthesis of aldosterone from deoxycorticosterone were
      investigated kinetically in the membrane-reconstituted system with bovine
      cytochrome P45011 beta at 37 degrees C. Reaction rapid-quenching experiments for
      the metabolism of deoxycorticosterone by P45011 beta showed that aldosterone was
      produced via corticosterone, not via 18-hydroxydeoxycorticosterone. The kinetic
      analysis revealed that aldosterone was formed successively from fractions of
      intermediate metabolites which did not dissociate from P45011 beta. The rate of
      each reaction step in the successive reactions was estimated from the combination
      of results of the rapid-quenching experiments and the metabolism of
      deoxycorticosterone in the presence of an excess amount of substrate, in which
      the dissociation of final product, aldosterone, from the enzyme was the slowest
      step in the synthesis from deoxycorticosterone. Under steady-state reaction
      conditions, the interaction of P45011 beta with P450scc stimulates the production
      of corticosterone from deoxycorticosterone by about 10-fold but inhibits further
      reactions from corticosterone. The rapid-quenching experiments showed, however,
      that the rate constant for the 11 beta-hydroxylation of deoxycorticosterone for
      corticosterone production in the presence of P450scc was almost the same as that
      without P450scc. The interaction of P45011 beta with P450scc in the reaction
      system for deoxycorticosterone metabolism was found to slow the rate of the
      subsequent 18-hydroxylation of the produced corticosterone and to accelerate the
      dissociation of the corticosterone from P45011 beta, which stimulated the
      corticosterone production and inhibited the further reaction for aldosterone
      synthesis in the steady-state reaction.

PMID- 9609706
TI  - The S0 state EPR signal from the Mn cluster in photosystem II arises from an
      isolated S = 1/2 ground state.
AB  - During oxygen evolution, the Mn cluster in Photosystem II cycles through five
      oxidation states, S0-S4. S0 and S2 are paramagnetic, and can be monitored by
      electron paramagnetic resonance (EPR). Recently a new EPR signal from the S0
      state was discovered [Ahrling et al. (1997) Biochemistry 36, 13148-13152,
      Messinger et al. (1997) J. Am. Chem. Soc. 119, 11349-11350]. Here, we present a
      well-resolved S0 spectrum, taken at high power and low temperature. The spectrum
      is wider and more resolved than previously thought, with structure over more than
      2500 G, and appears to have at least 20 reproducible peaks on each side of g = 2.
      We also present the temperature dependence of the unsaturated S0 signal
      amplitude. A linear relationship was found between signal intensity and
      reciprocal temperature (1/T) in the region 5-25 K, clearly extrapolating to 0.
      This obeys the Curie law, indicating that the S0 state is a ground S = 1/2 state
      with no thermally accessible excited state. The data are consistent with a
      minimum energy gap of 30 cm-1 between the ground and first excited states.

PMID- 9609705
TI  - Interactions between the cytochrome b, cytochrome c1, and Fe-S protein subunits
      at the ubihydroquinone oxidation site of the bc1 complex of Rhodobacter
      capsulatus.
AB  - Ubihydroquinone:cytochrome (cyt) c oxidoreductase (bc1 complex and its plant
      counterpart b6f complex) is a vital component of energy-transducing systems in
      most organisms from bacteria to eukaryotes. In the facultative phototrophic (Ps)
      bacterium Rhodobacter capsulatus, it is constituted by the cyt b, cyt c1, and
      Rieske Fe-S protein subunits and is essential for Ps growth. Of these subunits,
      cyt b has two nontransmembrane helices, cd1 and cd2, which are critical for its
      structure and function. In particular, substitution of threonine (T) at position
      163 on cd1 with phenylalanine (F) or proline (P) leads to the absence of the bc1
      complex. Here, Ps+ revertants of B:T163F were obtained, and their detailed
      characterizations indicated that position 163 is important for the assembly of
      the bc1 complex by mediating subunit interactions at the Qo site. The loss of the
      hydroxyl group at position 163 of cyt b was compensated for by the gain of either
      a hydroxyl group at position 182 of cyt b or 46 of the Fe-S protein or a
      sulfhydryl group at position 46 of cyt c1. Examination of the mitochondrial bc1
      complex crystal structure [Zhang, Z., Huang, L., Shulmeister, V. M., Chi, Y.-I.,
      Kim, K. K., Hung, L.-W., Crofts, A. R., Berry, E. A., and Kim, S.-H. (1998)
      Nature 392, 677-684] revealed that the counterparts of B:G182 (i.e., G167) and
      F:A46 (i.e. , A70) are located close to B:T163 (i.e., T148), whereas the C:R46
      (i.e., R28) is remarkably far from it. The revertants contained substoichiometric
      amounts of the Fe-S protein subunit and exhibited steady-state and single
      turnover, electron transfer activities lower than that of a wild-type bc1
      complex. Interestingly, their membrane supernatants contained a smaller form of
      this subunit with physicochemical properties identical to those of its membrane
      bound form. Determination of the amino-terminal amino acid sequence of this
      soluble Fe-S protein revealed that it was derived from the wild-type protein by
      proteolytic cleavage at V44. This work revealed for the first time that position
      163 of cyt b is important both for proper subunit interactions at the Qo site and
      for inactivation of the bc1 complex by proteolytic cleavage of its Fe-S protein
      subunit at a region apparently responsible for its mobility during Qo site
      catalysis.

PMID- 9609707
TI  - Conformation and ion-channeling activity of a 27-residue peptide modeled on the
      single-transmembrane segment of the IsK (minK) protein.
AB  - IsK (minK) protein, in concert with another channel protein KVLQT1, mediates a
      distinct, slowly activating, voltage-gated potassium current across certain
      mammalian cell membranes. Site-directed mutational studies have led to the
      proposal that the single transmembrane segment of IsK participates in the pore of
      the potassium channel [Takumi, T. (1993) News Physiol. Sci. 8, 175-178]. We
      present functional and structural studies of a short peptide (K27) with primary
      structure NH2-1KLEALYILMVLGFFGFFTLGIMLSYI27R-COOH, corresponding to the
      transmembrane segment of IsK (residues 42-68). When K27 was incorporated, at low
      concentrations, into phosphatidylethanolamine, black-lipid membranes, single
      channel activity was observed, with no strong ion selectivity. IR measurements
      reveal the peptide has a predominantly helical conformation in the membrane. The
      atomic resolution structure of the helix has been established by high-resolution
      1H NMR spectroscopy studies. These studies were carried out in a solvent
      comprising 86% v/v 1,1,1,3,3,3-hexafluoro-isopropanol-14% v/v water, in which the
      IR spectrum of the peptide was found to be very similar to that observed in the
      bilayer. The NMR studies have established that residues 1-3 are disordered, while
      residues 4-27 have an alpha-helical conformation, the helix being looser near the
      termini and more stable in the central region of the molecule. The length (2. 6
      nm) of the hydrophobic segment of the helix, residues 7-23, matches the span of
      the hydrocarbon chains (2.3 +/- 0.25 nm) of fully hydrated bilayers of
      phosphatidylcholine lipid mixture from egg yolk. The side chains on the helix
      surface are predominantly hydrophobic, consistent with a transmembrane location
      of the helix. The ion-channeling activity is believed to stem from long-lived
      aggregates of these helices. The aggregation is mediated by the pi-pi stacking of
      phenylalanine aromatic rings of adjacent helices and favorable interactions of
      the opposing aliphatic-like side chains, such as leucine and methionine, with the
      lipid chains of the bilayer. This mechanism is in keeping with site-directed
      mutational studies which suggest that the transmembrane segment of IsK is an
      integral part of the pore of the potassium channel and has a similar disposition
      to that in the peptide model system.

PMID- 9609708
TI  - Reconstitution of the iterative type II polyketide synthase for tetracenomycin F2
      biosynthesis.
AB  - The tetracenomycin polyketide synthase (TCM PKS), a type II complex, produces TCM
      F2, a precursor of TCM C in Streptomyces glaucescens, and consists of at least
      the TcmK, -L, -M, and -N proteins. The TcmK/TcmL ketosynthase subunits were
      purified from overexpression of their genes in Streptomyces lividans. TcmK
      (calculated molecular mass 45 kd) and TcmL (calculated molecular mass 42 kd)
      function as a heterodimeric alphabeta complex based on observing that only the
      purified complex complemented TCM PKS activity in protein extracts made from
      strains bearing tcmK or tcmL deletion mutants to make TCM F2 in vitro, and that
      the molecular mass of the purified complex was 90 kd as estimated by gel
      filtration chromatography. The TCM PKS activity was reconstituted with purified
      protein components, indicating that the minimal set of proteins required to make
      TCM F2 included the ketosynthase complex (TcmKL), an acyl carrier protein (TcmM),
      a malonyl CoA:ACP acyltransferase (MAT), and a cyclase (TcmN). The MAT was
      required to catalyze the transacylation between malonyl-CoA and TcmM, although a
      relatively slow spontaneous transacylation also occurred in a reaction without
      the MAT. Acetyl-CoA, the proposed starter unit for the TCM PKS, was not required
      for the production of TCM F2 in vitro, although it could be incorporated into
      this polyketide to a small extent. TcmJ, a PKS protein without a known function,
      greatly increased the production of TCM F2 but could not replace TcmN as a
      cyclase in the reconstituted system.

PMID- 9609709
TI  - Folding of circular and permuted chymotrypsin inhibitor 2: retention of the
      folding nucleus.
AB  - The 64-residue chymotrypsin inhibitor 2 (CI2) folds by a two-state nucleation
      condensation mechanism, whereby secondary and tertiary structure coalesce
      concomitantly in the transition state around Ala 16 in the helical N-cap.
      Permutation of the SH3-domain of alpha-spectrin apparently shifts its folding
      nucleus to another region of the protein, suggesting that a protein's transition
      state may be altered by altering the protein's connectivity. We have
      characterized the structure of the transition state of a circular and a permuted
      version of CI2 by a protein engineering study encompassing 11 mutations. Circular
      CI2 was obtained by the introduction of cysteines at residues 3 and 63 and
      linking them by disulfide bond formation. Subsequent cyanogen-bromide cleavage of
      the scissile bond, Met 40-Glu 41, yielded permuted CI2. Circular and permuted CI2
      also fold according to a two-state mechanism. Permutation does not affect the
      folding rate constant, but circularization increases it 7-fold. The transition
      states of circular and permuted CI2 are essentially unchanged from that of wild
      type CI2. Importantly, the folding nucleus around Ala16 is retained. These
      results complement a previous observation that the transition state for
      association of two CI2 fragments (residues 1-40 and 41-64, generated by CNBr
      cleavage) is very similar to the folding transition state of intact CI2. The
      similarity of rate constants for folding of wild-type and permuted CI2, and their
      value relative to that for the association of fragments, allows us to estimate
      the gain in entropy of activation on having the separate fragments linked: 18.3
      cal M-1 K-1; i.e. an effective molarity of 10(4) M. The contrast between the
      retention of the folding nucleus on permutation of CI2 and its change for the SH3
      domain of alpha-spectrin probably arises because the latter was cleaved in its
      folding nucleus whereas cleavage at sites other than 40-41 in CI2 is very
      destabilizing. Whether or not a folding nucleus can be changed probably depends
      on the specific protein and its permissivity to permutation.

PMID- 9609710
TI  - Denaturation of type I collagen fibrils is an endothermic process accompanied by
      a noticeable change in the partial heat capacity.
AB  - Thermal transitions of type I collagen fibrils were investigated by differential
      scanning calorimetry and spectrophotometry of turbidity within a wide range of
      external conditions. The advanced microcalorimeter allowed us to carry out the
      measurements at low concentrations of collagen (0.15-0.3 mg/mL). At these
      concentrations of collagen and under fibril-forming conditions, the melting
      curves display two pronounced heat adsorption peaks (at 40 and 55 degreesC). The
      low-temperature peak was assigned to the melting of monomeric collagen, while the
      high-temperature peak was assigned to the denaturation of collagen fibrils. It
      was shown that the denaturation of fibrils, in contrast to the monomeric
      collagen, is accompanied by a noticeable change in the partial specific heat
      capacity. Surprisingly, comparison of the collagen calorimetric curves in the
      fibril-forming and nonforming conditions revealed that DeltaCp of fibril
      denaturation is caused by a decrease in the Cp of collagen at premelting
      temperatures. This suggests the existence of an intermediate structural state of
      collagen in a transparent solution preceding fibril formation. Our study also
      shows that collagen fibrils formed prior to heating have thermodynamic parameters
      different from those of fibrils formed and denatured during heating in the
      calorimeter. Analysis of the data allowed us to determine the denaturation
      enthalpy of the mature fibrils and to conclude that the enthalpy plays a more
      important role in fibril stabilization than was previously assumed. The observed
      large DeltaCp value of fibril denaturation as well as the difference between
      thermodynamic parameters of the mature and newly formed fibrils is readily
      explained by the presence of water molecules in the fibril structure.

PMID- 9609711
TI  - The orientation of nisin in membranes.
AB  - Nisin is a 34 residue long peptide belonging to the group A lantibiotics with
      antimicrobial activity against Gram-positive bacteria. The antimicrobial activity
      is based on pore formation in the cytoplasmic membrane of target organisms. The
      mechanism which leads to pore formation remains to be clarified. We studied the
      orientation of nisin via site-directed tryptophan fluorescence spectroscopy.
      Therefore, we engineered three nisin Z variants with unique tryptophan residues
      at positions 1, 17, and 32, respectively. The activity of the tryptophan mutants
      against Gram-positive bacteria and in model membrane systems composed of DOPC or
      DOPG was established to be similar to that of wild type nisin Z. The tryptophan
      fluorescence emission maximum showed an increasing blue-shift upon interaction
      with vesicles containing increased amounts of DOPG, with the largest effect for
      the 1W peptide. Studies with the aqueous quencher acrylamide showed that all
      tryptophans became inaccessible from the aqueous phase in the presence of
      negatively charged lipids in the vesicles. From these results it is concluded
      that anionic lipids mediate insertion of the tryptophan residues in at least
      three positions of the molecule into the lipid bilayer. The depth of insertion of
      the tryptophan residues was determined via quenching of the tryptophan
      fluorescence by spin-labeled lipids. The results showed that the depth of
      insertion was dependent on the amount of negatively charged lipids. In membranes
      containing 50% DOPG, the distances from the bilayer center were determined to be
      15.7, 15.0, and 18.4 A for the tryptophan at position 1, 17, and 32,
      respectively. In membranes containing 90% DOPG, these distances were calculated
      to be 10.8, 11.5, and 13.1 A, respectively. These results suggest an overall
      parallel average orientation of nisin in the membrane, with respect to the
      membrane surface, with the N-terminus more deeply inserted than the C-terminus.
      These data were used to model the orientation of nisin in the membrane.

PMID- 9609712
TI  - Solution structure of the ternary complex between aminoacyl-tRNA, elongation
      factor Tu, and guanosine triphosphate.
AB  - Complex formation between elongation factor Tu (EF-Tu), Phe-tRNAPhe, and GTP was
      analyzed by small-angle neutron and X-ray scattering methods. Both techniques
      show that the ternary complex consists of one EF-Tu and one aminoacyl-tRNA. No
      shift in stoichiometry was detected when the temperature was raised from 5 to 37
      degreesC, in contrast to previous observations obtained from RNase A protection
      experiments [Bilgin and Ehrenberg (1995) Biochemistry34, 715-719]. A small but
      significant increase in the radius of gyration of the complex was observed when
      the temperature was decreased from 37 to 5 degreesC. The X-ray solution
      scattering patterns were compared with those calculated from the crystal
      structure of the complex formed between EF-Tu from Thermus aquaticus and Phe
      tRNAPhe from yeast. The comparison shows that the solution structure of the
      ternary complex, formed entirely from Escherichia coli components and under
      translationally optimal buffer conditions, is very close to the crystal
      structure, formed from heterologous components under very different conditions.
      Furthermore, for the hybrid complex in solution there is no evidence for the
      formation of trimers as suggested by the crystal structure.

PMID- 9609713
TI  - DNA curvature in solution measured by fluorescence resonance energy transfer.
AB  - The sequence-induced curvature of DNA fragments free in solution was
      characterized by measurements of the end-to-end distance using fluorescence
      resonance energy transfer (FRET). The 31 bp oligonucleotides were labeled at
      their 5' ends with fluorescein as the donor and rhodamine X as the acceptor. We
      compared a curved oligonucleotide with three phased A6 blocks and a control
      containing (AT)3 instead of the A6 blocks. The increased efficiency of energy
      transfer of the A6-containing DNA indicates the existence of a permanent sequence
      induced curvature, the magnitude of which is in good agreement with estimates
      from theoretical curvature predictions. Energy transfer efficiency and
      correspondingly curvature increases with NaCl concentration.

PMID- 9609714
TI  - Location of diphenylhexatriene (DPH) and its derivatives within membranes:
      comparison of different fluorescence quenching analyses of membrane depth.
AB  - The average membrane location of a series of diphenylhexatriene (DPH)-derived
      membrane probes was analyzed by measuring the quenching of DPH fluorescence with
      a series of nitroxide-labeled lipids in which the depth of the nitroxide group is
      varied. All DPH derivatives were located deeply within the bilayer. Some
      derivatives were anchored at a shallower depth than free DPH by attachment to
      cationic or anionic groups. However, the absolute change in DPH depth upon
      attachment to such groups was relatively modest (<4 A). In fact, protonated DPH
      fatty acid and a DPH fatty acyl group attached to a phosphatidylcholine were
      found to locate slightly more deeply than free DPH. The location of DPH
      derivatives can be explained by the length of the DPH group and its tendency to
      orient predominantly parallel to the fatty acyl chains of the bilayer. These
      factors allow a charged group attached to one end of a DPH molecule to be
      accommodated at the polar surface while maintaining a deep DPH location.
      Basically, it appears that most DPH derivatives probe the same region in the
      bilayer. We conclude previously reported differences in fluorescence polarization
      of free and anchored forms of DPH may reflect a direct effect of anchoring on
      motion rather than an effect on average DPH location. Other experiments showed
      the localization of DPH probes was found to be similar in the presence and
      absence of cholesterol. This implies that previously observed cholesterol-induced
      effects on DPH fluorescence polarization also largely reflect differences in DPH
      motion, not DPH location. From the quenching results it was also possible to
      define rules governing the location of a variety of chemical groups in membranes
      by comparison of the results obtained with DPH derivatives to those of similar
      derivatives of other fluorescent groups. Finally, an important goal of this study
      was to compare different methods of analysis of quenching data: parallax
      analysis, distribution (Gaussian) analysis (using a single Gaussian), and a
      second-order polynomial analysis. To evaluate the accuracy of these methods, the
      apparent depths of a series of fluorescence probes previously analyzed by
      parallax analysis was reanalyzed with all three methods. There was good agreement
      unless the fluorescent molecule was very shallow or very deep. In such cases,
      only parallax analysis gave physically reasonable results. This is likely to be
      due to the lack of a sufficient number of quenchers spanning a wide enough range
      for other analyses to compensate for deviations from ideal curves. Parallax
      analysis was also compared to distribution (Gaussian) analysis using a double
      Gaussian fit to account for quenching from the trans leaflet (Ladokhin, A. (1997)
      Methods Enzymol. 278, 462-473). Again more physically reasonable results were
      obtained from parallax analysis, likely due to non-Gaussian behavior of the depth
      dependence of quenching. Notwithstanding these observations, the significant
      number of cases where Gaussian curve fitting methods for quenching analysis are
      most powerful are discussed.

PMID- 9609715
TI  - Sulfhydryl oxidation of mutants with cysteine in place of acidic residues in the
      lactose permease.
AB  - To examine further the role of charge-pair interactions in the structure and
      function of lactose permease, Asp237 (helix VII), Asp240 (helix VII), Glu126
      (cytoplasmic loop IV/V), Glu269 (helix VIII), and Glu325 (helix X) were replaced
      individually with Cys in a functional mutant devoid of Cys residues. Each mutant
      was then oxidized with H2O2 in order to generate a sulfinic and/or sulfonic acid
      at these positions. Due to the isosteric relationship between aspartate and
      sulfinate, in particular, and the lower pKa of the sulfinic and sulfonic acid
      side chains, oxidized derivatives of Cys are useful probes for examining the role
      of carboxylates. Asp237-->Cys or Asp240-->Cys permease is inactive, as shown
      previously, but H2O2 oxidation restores activity to an extent similar to that
      observed when a negative charge is reintroduced by other means. Glu126-->Cys,
      Glu269-->Cys, or Glu325-->Cys permease is inactive, but oxidation does not
      restore active lactose transport. The data are consistent with previous
      observations indicating that Asp237 and Asp240 are not critical for active
      lactose transport, while Glu126, Glu269, and Glu325 are irreplaceable. Although
      Glu269-->Cys permease does not transport lactose, the oxidized mutant exhibits
      significant transport of beta,D-galactosylpyranosyl 1-thio-beta,D
      galactopyranoside, a property observed with Glu269-->Asp permease. The
      observation supports the idea that an acidic residue at position 269 is important
      for substrate recognition. Finally, oxidized Glu325-->Cys permease catalyzes
      equilibrium exchange with an apparent pKa of about 6.5, more than a pH unit lower
      than that observed with Glu325-->Asp permease, thereby providing strong
      confirmatory evidence that a negative charge at position 325 determines the rate
      of translocation of the ternary complex between the permease, substrate, and H+.

PMID- 9609716
TI  - Specific cross-links between fragments of proteolyzed Na,K-ATPase induced by o
      phthalaldehyde.
AB  - We have used o-phthalaldehyde (OPA) to cross-link adjacent fragments of "19 kDa
      membranes", a tryptic preparation of Na,K-ATPase lacking the ATP site but
      retaining cation occlusion sites. Treatment with OPA of "19 kDa membranes" or
      detergent-solubilized membranes containing occluded Rb ions [Or, E., Goldshleger,
      R., Tal, D. M., and Karlish, S. J. D. (1996) Biochemistry 35, 6853-6864] yielded
      cross-linked products of 25 and 31 kDa. Both species contained the 19 kDa
      fragment of the alpha subunit (transmembrane segments M7-M10). In addition, the
      25 kDa product contained the fragment including M5-M6, while the 31 kDa product
      contained a 16 kDa fragment of the beta subunit. Cross-linking was unaffected by
      the absence or presence of ligands (Na, Rb, or Mg and ouabain). Cross-linking was
      largely abolished in thermally inactivated "19 kDa membranes". When proteolytic
      digestion of the 25 and 31 kDa products was combined with antibody binding, PKA
      dependent phosphorylation, and sequencing of fragments, approximate positions of
      the cross-links were established. In the 25 kDa product, the cross-link was
      located within the short cytoplasmic segment Asn831-Arg841 of the 19 kDa fragment
      preceding M7 and within Ala749-Ala770 preceding M5. Thus, M7 and M5 are likely to
      be in close proximity. In the 31 kDa product, the cross-link was located in the
      extracellular loop of the alpha subunit between M7 and M8, close to residues
      which are known to interact with the beta subunit. Functional implications of the
      interactions between the fragments of the alpha (M5-M6 and M7-M10) and beta
      subunits are discussed.

PMID- 9609717
TI  - The solution structure of human coagulation factor VIIa in its complex with
      tissue factor is similar to free factor VIIa: a study of a heterodimeric receptor
      ligand complex by X-ray and neutron scattering and computational modeling.
AB  - Factor VIIa (FVIIa) is a soluble four-domain plasma serine protease coagulation
      factor that forms a tight complex with the two extracellular domains of the
      transmembrane protein tissue factor in the initiating step of blood coagulation.
      To date, there is no crystal structure for free FVIIa. X-ray and neutron
      scattering data in solution for free FVIIa and the complex between FVIIa and
      soluble tissue factor (sTF) had been obtained for comparison with crystal
      structures of the FVIIa-sTF complex and of free factor IXa (FIXa). The solution
      structure of free FVIIa as derived from scattering data is consistent with the
      extended domain arrangement of FVIIa seen in the crystal structure of its complex
      with sTF, but is incompatible with the bent, less extended domain conformation
      seen in the FIXa crystal structure. The FVIIa scattering curve is also compatible
      with a subset of 317 possible extended structures derived from a constrained
      automated conformational search of 15 625 FVIIa domain models. Thus, the
      scattering data support extended domain models for FVIIa free in solution.
      Similar analyses showed that the solution scattering derived and crystal
      structures of the FVIIa-sTF complex were in good agreement. An automated
      constrained search for allowed structures for the complex in solution based on
      scattering curves showed that only a small family of compact models gave good
      agreement, namely those in which FVIIa and sTF interact closely over a large
      surface area. The general utility of this approach for structural analysis of
      heterodimeric complexes in solution is discussed. Analytical ultracentrifugation
      data and the modeling of these data were consistent with the scattering results.
      It is concluded that in solution FVIIa has an extended or elongated domain
      structure, which allows rapid interaction with sTF over a large surface area to
      form a high-affinity complex.

PMID- 9609718
TI  - Bypass of a site-specific cis-Syn thymine dimer in an SV40 vector during in vitro
      replication by HeLa and XPV cell-free extracts.
AB  - The key step in skin cancer induction by UV light is thought to be the mutagenic
      DNA synthesis past a DNA photoproduct in a proto-oncogene or tumor suppressor
      gene. To investigate this critical step, we have constructed an SV40 vector
      containing a cis-syn thymine dimer, the major DNA photoproduct induced by UVB
      light, within an AseI site at a location that would initially be replicated by
      leading strand synthesis. When the dimer-containing SV40 vector was incubated
      with cell-free HeLa extracts in the presence of TAg, and then digested with AseI,
      a 2325 bp fragment corresponding to inhibition of cleavage at the dimer site was
      observed, suggesting that the dimer had terminated synthesis and/or had been
      bypassed. When the reaction was limited to one round of replication and the
      products of restriction enzyme digestion were examined by denaturing gel
      electrophoresis, bands corresponding to both termination and bypass were observed
      in roughly a one-to-one ratio. Whereas increasing the dNTP concentration from 10
      microM to 1 mM increased the ratio of bypass to termination from 0.6 to 2.6, it
      had no effect on the site of termination, which occurred exclusively one
      nucleotide before the dimer. Experiments in which dGTP was held constant at 25
      microM and various combinations of the remaining nucleotides were raised from 25
      microM to 1 mM showed substantial increases in the bypass-to-termination ratio,
      with the greatest effect seen for raising all three nucleotides to 1 mM.
      Replication by primary fibroblast XPV extracts was also investigated and found to
      be greatly stimulated by rhRPA, whereas the stimulatory effect for HeLa cell
      extracts was variable. In the presence of rhRPA, the XPV extracts were also found
      to bypass the cis-syn dimer, which contrasts with a recent report that could not
      detect dimer bypass in SV40 transformed XPV extracts in the absence of added
      replication factors [Cordeiro-Stone, M., et al. (1997) J. Biol. Chem. 272, 13945
      13954].

PMID- 9609719
TI  - The chromophore induces a correct folding of the polypeptide chain of
      bacteriorhodopsin.
AB  - The pK values of the Schiff bases of several bacteriorhodopsin (BR) preparations
      have been determined by titration. While for the native protein a high pK of 13
      has been reported [Druckmann et al. (1982) Biochemistry 21, 4953], we find that a
      BR reconstituted from retinal and the apoprotein obtained from the retinal
      deficient strain JW5 exhibits a low pK value, 8.5. When the retinal chromophore
      is added to growing JW5 cells leading to in vivo BR formation, this BR shows a
      high Schiff base pK, >/=10.2. A value of 9.3 was determined when BR was
      reconstituted from retinal and BO, obtained from bleaching BR with hydroxylamine.
      A low pK value of 8.1 was found when 13-trifluoro(CF3)-retinal was used as
      chromophore for in vitro reconstitution [Sheves et al. (1986) Proc. Natl. Acad.
      Sci. U.S.A. 83, 3262], which is confirmed in this study. When we add CF3-retinal
      to growing JW5 cells, this low pK shifts to 9.1. Besides wild-type protein, the
      apoprotein from the mutant D96N (from the chromophore-deficient strain L-07) was
      also used for in vitro reconstitution with either chromophore, retinal or CF3
      retinal. Irrespective of the chromophore used, both mutant BRs exhibit low pK
      values of their Schiff bases of 8.1. Flash photolysis with respect to the rise
      and decay of the M-photocycle intermediate of wild-type and D96N-mutated BR
      carrying retinal and CF3-retinal revealed that in both proteins the incorporation
      of the trifluororetinal leads to a faster rise of the M-intermediate and to a
      slower decay. Since the apoprotein from the chromophore-deficient JW5 strain of
      H. salinarium, despite its lower boyant density, is arranged into trimers
      (according to CD measurements), we propose that the high pK value of the BR
      Schiff base is induced by long-distance interactions between BR molecules in the
      purple membrane patches which control the pK of the chromophore.

PMID- 9609720
TI  - Structural and functional analysis of the homing endonuclease PI-sceI by limited
      proteolytic cleavage and molecular cloning of partial digestion products.
AB  - PI-SceI is a member of an unusual class of rare cutting homing endonucleases
      produced by an autocatalytic protein splicing from a precursor. To analyze the
      structural and functional domain organization of the endonuclease PI-SceI and to
      examine whether the DNA binding activity can be structurally separated from the
      catalytic activity, we performed limited proteolytic digestion experiments with
      various proteases. Two protease-resistant fragments spanning the N- and C
      terminal halves of the nuclease were identified using different proteases which
      cleave the protein in the same region. Each fragment contains one of the two
      conserved LAGLIDADG motifs. The products of the limited proteolytic digests were
      shown to remain associated and to exhibit specific DNA binding but to be inactive
      in DNA cleavage. Different from what is observed with native PI-SceI, only one
      complex is formed as shown in an electrophoretic mobility shift assay. Expression
      clones for the N- and C-terminal protein fragments obtained by tryptic digestion
      were constructed, and the proteins PI-SceI-N and PI-SceI-C were purified. Only PI
      SceI-N exhibits DNA binding activity. Bending experiments with PI-SceI-N, a
      mixture of PI-SceI-N and PI-SceI-C, as well as the products of the limited
      tryptic digest show that a DNA substrate with the full length recognition
      sequence is bent by 45;. This degree of bending is also observed with a DNA
      containing only the right side of the recognition sequence, corresponding to one
      of the DNA cleavage products of PI-SceI. Our results demonstrate that the N
      terminal half of PI-SceI which lacks one of the two LAGLDADG motifs is able to
      bind to DNA specifically and to induce one of the distortions observed to occur
      in the process of DNA binding by PI-SceI. These results are discussed in light of
      the recently solved crystal structure of PI-SceI and used to refine a model for
      the mechanism of DNA binding and cleavage by PI-SceI.

PMID- 9609721
TI  - Kinetic mechanism and intrinsic isotope effects for the peptidylglycine alpha
      amidating enzyme reaction.
AB  - The bifunctional peptidylglycine alpha-amidating enzyme catalyzes the C-terminal
      amidation of glycine-extended peptides. The first enzyme activity,
      peptidylglycine alpha-hydroxylating monooxygenase, catalyzes the oxygen-,
      ascorbate-, and copper-dependent formation of alpha-hydroxyglycine derivatives.
      These are substrates for the second enzyme activity, peptidylamidoglycolate
      lyase, which catalyzes their breakdown to the corresponding C-terminal amidated
      peptide and glyoxylate as final products. Kinetic and isotope effect studies were
      carried out with N-benzoylglycine as a substrate at pH 6.0 using monofunctional
      and bifunctional monooxygenase activities. Kinetic data indicate an equilibrium
      ordered mechanism, with hippuric acid binding first followed by oxygen. A
      potentially important difference between the two monooxygenase activities is that
      product release occurs more slowly from the bifunctional enzyme, indicating an
      influence of the lyase domain on release of alpha-hydroxyglycine product to
      solution. Intrinsic isotope effects for the C-H bond cleavage were measured for
      the monofunctional form of the enzyme using a double-label tracer method,
      yielding 10.6 +/- 0.8 and 1.20 +/- 0.03 for the primary and alpha-secondary
      deuterium intrinsic isotope effects, respectively. These values are identical to
      previous measurements for the analogous enzyme system, dopamine beta
      monooxygenase [Miller, S. M., and Klinman, J. P. (1985) Biochemistry 24, 2114
      2127]. The identity of intrinsic isotope effects for peptidylglycine alpha
      hydroxylating monooxygenase and dopamine beta-monooxygenase with substrates of
      comparable reactivity (N-benzoylglycine and dopamine, respectively) extends
      similarities between the two enzymes significantly beyond sequence homology and
      cofactor requirements.

PMID- 9609722
TI  - Constitutive activation of opsin by mutation of methionine 257 on transmembrane
      helix 6.
AB  - Rhodopsin is a member of the large family of G protein-coupled receptors
      (GPCR's). Constitutive activity of GPCR's, defined as ligand-independent
      signaling, has been recognized as an important feature of receptor function and
      has also been implicated in the molecular pathophysiology of a number of human
      diseases. Rhodopsin has evolved a unique mechanism to minimize receptor basal
      activity. The chromophore 11-cis-retinal, which acts as an inverse agonist in
      rhodopsin, is covalently bound to the receptor to ensure extremely low receptor
      signaling in the dark. In this study, we replaced Met257 in TM helix 6 of opsin
      with each of the remaining 19 amino acids. Only mutant opsin M257R failed to be
      expressed in COS-cell membranes. Each of the remaining 18 mutant opsins, with the
      exception of M257L, was significantly constitutively active. Two mutants in
      particular, M257Y and M257N, displayed very high levels of constitutive activity.
      In addition, the double-site mutants with substitutions of both Met257 and Glu113
      in TM helix 3 tended to be much more constitutively active than the sums of the
      activities of the individual single-site mutants. Based on existing structural
      models of rhodopsin, we conclude that Met257 may form an important and specific
      interhelical interaction with a highly conserved NPXXY motif in TM helix 7, which
      stabilizes the inactive receptor conformation by preventing TM helix 6 movement
      in the absence of all-trans-retinal. Furthermore, we are able to show that the
      pharmacological properties of the large number (approximately 50) of mutant
      opsins that we have characterized to date support the two-state model of GPCR
      function. These results suggest that rhodopsin and other GPCR's share a common
      mechanism of receptor activation that involves specific changes in helix-helix
      interactions.

PMID- 9609724
TI  - Fluoride binding in hemoproteins: the importance of the distal cavity structure 

PMID- 9609723
TI  - Structures and dynamic motion of laminin-1 as observed by atomic force
      microscopy.
AB  - Laminins are a family of multifunctional extracellular matrix glycoproteins that
      play important roles in the development and maintenance of tissue organization
      via their interactions with cells and other extracellular matrix proteins. To
      understand the structural basis of laminins' functions, we examined the motion of
      laminin-1 (Ln-1) in physiological buffers using atomic force microscopy. While
      many Ln-1 molecules assumed the expected cruciform structure, unexpected dynamic
      movements of the Ln-1 arms were observed in aqueous environments. These dynamic
      movements of the Ln-1 arms may contribute to the diversity of laminin functions.

PMID- 9609725
TI  - A urokinase receptor mRNA binding protein from rabbit lung fibroblasts and
      mesothelial cells.
AB  - The urokinase receptor (uPAR) influences several biological functions relevant to
      lung injury and repair, including proteolysis, cell migration, and adhesion. In
      malignant mesothelioma cells, we recently found that a posttranscriptional
      mechanism involving a cis-trans interaction between a uPAR mRNA sequence and a
      cytoplasmic uPAR mRNA binding protein (mRNABP) regulates uPAR gene expression (S.
      Shetty, A. Kumar, and S. Idell. Mol. Cell Biol. 17: 1075-1083, 1997). In this
      study, we sought to determine if uPAR expression in lung and pleural cells
      involves a similar posttranscriptional pathway. We first identified and
      characterized the uPAR mRNABP in rabbit tissues using gel mobility shift,
      ultraviolet (UV) cross-linking, and RNase protection assays and detected it in
      liver, heart, brain, spleen, colon, and lung. Phorbol 12-myristate 13-acetate,
      lipopolysaccharide, transforming growth factor-beta, tumor necrosis factor-alpha,
      or cycloheximide induced uPAR and uPAR mRNA expression in cultured rabbit pleural
      mesothelial cells and lung fibroblasts and concurrently reduced the uPAR mRNA
      uPAR mRNABP interaction. Using conventional and affinity chromatography, we
      purified a 50-kDa uPAR mRNABP that selectively binds to a 51-nucleotide fragment
      of the uPAR coding region. This protein migrates as a monomer when analyzed by
      SDS-PAGE and UV cross-linking and does not possess intrinsic RNase activity in
      vitro. A uPAR mRNABP physicochemically and functionally similar to that of human
      malignant mesothelioma is constitutively expressed in the rabbit lung and other
      nonneoplastic tissues. In rabbit lung fibroblasts and mesothelial cells,
      expression of uPAR involves posttranscriptional regulation whereby the uPAR
      mRNABP appears to interact with a specific coding region cis-element to decrease
      the stability of uPAR mRNA.

PMID- 9609726
TI  - Mechanical strain inhibits repair of airway epithelium in vitro.
AB  - The repair of airway epithelium after injury is crucial in restoring epithelial
      barrier integrity. Although the airway epithelium is stretched and compressed due
      to changes in both circumferential and longitudinal dimensions during respiration
      and may be overdistended during mechanical ventilation, the effect of cyclic
      strain on the repair of epithelial wounds is unknown. Human and cat airway
      epithelial cells were cultured on flexible membranes, wounded by scraping with a
      metal spatula, and subjected to cyclic strain using the Flexercell Strain Unit.
      Because the radial strain profile in the wells was nonuniform, we compared
      closure in regions of elongation and compression within the same well. Both
      cyclic elongation and cyclic compression significantly slowed repair, with
      compression having the greatest effect. This attenuation was dependent upon the
      time of relaxation (TR) during the cycle. When wells were stretched at 10
      cycles/min (6 s/cycle) with TR = 5 s, wounds closed similarly to wounds in static
      wells, whereas in wells with TR = 1 s, significant inhibition was observed. As
      the TR during cycles increased (higher TR), wounds closed faster. We measured the
      effect of strain at various TRs on cell area and centroid-centroid distance (CD)
      as a measure of spreading and migration. While cell area and CD in static wells
      significantly increased over time, the area and CD of cells in the elongated
      regions did not change. Cells in compressed regions were significantly smaller,
      with significantly lower CD. Cell area and CD became progressively larger with
      increasing TR. These results suggest that mechanical strain inhibits epithelial
      repair.

PMID- 9609727
TI  - Pseudomonas pyocyanine alters calcium signaling in human airway epithelial cells.
AB  - Pseudomonas aeruginosa, an opportunistic human pathogen, causes both acute and
      chronic lung disease. P. aeruginosa exerts many of its pathophysiological effects
      by secreting virulence factors, including pyocyanine, a redox-active compound
      that increases intracellular oxidant stress. Because oxidant stress has been
      shown to affect cytosolic Ca2+ concentration ([Ca2+]c) in other cell types, we
      studied the effect of pyocyanine on [Ca2+]c in human airway epithelial cells
      (A549 and HBE). At lower concentrations, pyocyanine inhibits inositol 1,4,5
      trisphosphate formation and [Ca2+]c increases in response to G protein-coupled
      receptor agonists. Conversely, at higher concentrations, pyocyanine itself
      increases [Ca2+]c. The pyocyanine-dependent [Ca2+]c increase appears to be
      oxidant dependent and to result from increased inositol trisphosphate and release
      of Ca2+ from intracellular stores. Ca2+ plays a central role in epithelial cell
      function, including regulation of ion transport, mucus secretion, and ciliary
      beat frequency. By disrupting Ca2+ homeostasis, pyocyanine could interfere with
      these critical functions and contribute to the pathophysiological effects
      observed in Pseudomonas-associated lung disease.

PMID- 9609728
TI  - PKC isoforms and other signaling proteins involved in surfactant secretion in
      developing rat type II cells.
AB  - We previously reported that there is a developmental increase in surfactant
      secretion in response to P2Y2 purinoceptor agonists. UTP does not stimulate
      secretion in type II cells from 1- or 2-day-old rats; there is a small response
      to UTP in cells from 4-day-old animals, and the response increases with
      increasing age thereafter. Second messenger formation in response to P2Y2
      agonists has a similar developmental pattern. We have investigated whether the
      failure to respond to P2Y2 agonists is due to a deficiency in the P2Y2 receptor
      or in downstream signaling factors. We compared type II cells from adult and 1-
      to 2-day-old rats with respect to expression of the P2Y2 receptor gene and the
      levels of phospholipase C-beta (PLC-beta) and protein kinase C (PKC) isomers and
      of the alpha-subunit of the GTP-binding protein Gq. We measured gene expression
      by reverse transcriptase-polymerase chain reaction and protein levels by
      immunoblotting. We identified PKC-alpha, -betaI, -betaII, -delta, -eta, -zeta, 
      theta, and -mu, PLC-beta3, and Gqalpha in adult and newborn type II cells. PKC
      epsilon, -gamma, and -lambda and PLC-beta1, -beta2, and -beta4 were not present
      in adult or newborn type II cells. Expression of the P2Y2 receptor gene was
      essentially the same in newborn and adult cells. However, the levels of PKC
      alpha, -betaI, -betaII, and -zeta in newborn type II cells were only 43-57% those
      of adult cells. The level of PKC-theta also tended to be lower in the newborn
      cells. There was little difference between newborn and adult type II cells in the
      levels of PKC-delta, -eta, and -mu, PLC-beta3, and Gqalpha. These data suggest
      that the lack of response of early newborn type II cells to P2Y2 agonists is not
      due to a lack of expression of the receptor gene but possibly to insufficient
      amounts of one or more of the alpha, betaI, betaII, or zeta PKC isoforms.

PMID- 9609729
TI  - Endothelial dysfunction in pulmonary arteries of patients with mild COPD.
AB  - To investigate whether endothelial dysfunction of pulmonary arteries (PA) is
      present in patients with mild chronic obstructive pulmonary disease (COPD) and to
      what extent it is related to the morphological abnormalities of PA, we studied 41
      patients who underwent lung resection. Patients were divided into the following
      groups: nonsmokers (n = 7), smokers with normal lung function (n = 13), and COPD
      (n = 21). Endothelium-dependent relaxation mediated by nitric oxide was evaluated
      in vitro in PA rings exposed to cumulative concentrations of acetylcholine (ACh)
      and ADP. Structural abnormalities of PA were assessed morphometrically. PA of
      COPD patients developed lower maximal relaxation in response to ADP than both
      nonsmokers and smokers (P < 0.05 each) and a trend to reduced relaxation in
      response to ACh (P = 0.08). Maximal relaxation to ADP correlated with the degree
      of airflow obstruction (r = 0.48, P < 0. 01). Morphometrical analysis of PA
      revealed thicker intimas, especially in small arteries, in both smokers and COPD
      compared with nonsmokers (P < 0.05 each). We conclude that endothelial
      dysfunction of PA is already present in patients with mild COPD. In these
      patients, as well as in smokers with normal lung function, small arteries show
      thickened intimas, suggesting that tobacco consumption may play a critical role
      in the pathogenesis of pulmonary vascular abnormalities in COPD.

PMID- 9609730
TI  - Effect of a novel covalent antithrombin-heparin complex on thrombin generation on
      fetal distal lung epithelium.
AB  - Respiratory distress syndrome is characterized by fibrin deposition in the lung.
      Fibrin adversely affects surfactant function and stimulates proliferation of
      fibroblasts. There is evidence that these properties may be important to the
      development of bronchopulmonary dysplasia. Despite successful initial treatment
      of neonatal respiratory distress syndrome with surfactant, the incidence of
      bronchopulmonary dysplasia has not decreased. In previous studies, it has been
      demonstrated that rat fetal distal lung epithelium (FDLE) possesses both
      procoagulant and anticoagulant properties. In this report, we have demonstrated
      (using factor VII-deficient plasma) that tissue factor is expressed on the FDLE
      surface and promotes thrombin generation. To regulate thrombin within this
      procoagulant environment, we have developed a novel anticoagulant, antithrombin
      heparin covalent complex (ATH) that can be retained within the lung after
      intrapulmonary instillation. We have demonstrated that ATH was superior to
      antithrombin plus standard heparin in suppressing thrombin generation (P < 0.001)
      and prothrombin consumption (P < 0.01) in recalcified defibrinated plasma on the
      surface of FDLE. Further studies with ATH in vivo need to be performed.

PMID- 9609731
TI  - Cytokine-induced nitric oxide formation in normal but not in neoplastic murine
      lung epithelial cell lines.
AB  - Cytomix, a mixture of interferon-gamma, tumor necrosis factor-alpha, and
      interleukin-1beta, induces nitric oxide (NO) production in lung epithelial cell
      lines. It is not known whether neoplastic transformation alters a cell's ability
      to form NO in response to cytokines. The present study investigated NO formation
      in two murine lines of immortalized "normal" (nontumorigenic) lung epithelial
      cells of alveolar type II origin, E10 and C10, and their sibling spontaneous
      transformants, E9 and A5. Nontumorigenic cells elaborated much more NO after
      cytomix exposure than did their tumorigenic counterparts. NO production was
      prevented by inhibiting protein synthesis and NO synthase and attenuated by
      dexamethasone. Northern and Western blot analyses of inducible NO synthase (iNOS)
      demonstrated cytomix-induced induction of iNOS only in nontumorigenic cells. The
      deficiency in NO production in tumorigenic cells was not associated with reduced
      iNOS mRNA stability or with differences in cytomix-induced nuclear factor-kappaB
      activation. Although cytomix caused a greater production of NO in E10 cells than
      in E9 cells, the same treatment induced equivalent proliferation in both cell
      lines. These results indicate a specific deficiency in cytokine-induced NO
      synthesis in transformed murine lung epithelial cells relative to their normal
      progenitor cells and provide a model for investigating iNOS regulation.

PMID- 9609732
TI  - Clearance of SP-C and recombinant SP-C in vivo and in vitro.
AB  - Surfactant protein (SP) C metabolism was evaluated in vivo by measurements of the
      clearance of bovine native SP-C (nSP-C) and a recombinant SP-C (rSP-C) in rabbits
      and mice and in vitro by the uptake into MLE-12 cells. rSP-C is the 34-amino acid
      human sequence with phenylalanine instead of cysteine in positions 4 and 5 and
      isoleucine instead of methionine in position 32. Alveolar clearances of iodinated
      SP-C and rSP-C after tracheal instillation were similar and slower than those for
      dipalmitoyl phosphatidylcholine (DPC) in the rabbit. nSP-C and rSP-C were cleared
      from rabbit lungs similarly to DPC, each with a half-life (t1/2) of approximately
      11 h. In mice, the clearance of rSP-C from the lungs was slower (t1/2 28 h) than
      the clearance of DPC (t1/2 12 h). Liposome-associated dinitrophenyl-labeled rSP-C
      was taken up by MLE-12 cells, and the uptake was inhibited by excess nSP-C. The
      pattern of inhibition of dinitrophenyl-rSP-C uptake by SP-B, but not by SP-A, was
      similar to that previously reported for nSP-C. Clearance kinetics of nSP-C were
      similar to previous measurements of pulmonary clearance of SP-B in rabbits and
      mice. rSP-C has clearance kinetics and uptake by cells similar to those of nSP-C.

PMID- 9609733
TI  - Transcriptional regulation of tropoelastin expression in rat lung fibroblasts:
      changes with age and hyperoxia.
AB  - Elastic fibers are thought to provide structural support for secondary septa as
      the lung undergoes the transition from the saccular to the alveolar stage. The
      synthesis of the soluble precursor of elastin, tropoelastin, occurs during a
      finite developmental period. We have investigated the developmental regulation of
      tropoelastin gene transcription and mRNA expression in fetal and postnatal rat
      lung fibroblasts and have assessed the changes in tropoelastin gene expression
      caused by hyperoxic exposure during secondary septal development. With the use of
      an RT-PCR assay and intron-specific primers to detect heterogeneous nuclear RNA
      (hnRNA) and intron-spanning primers to detect mRNA in freshly isolated rat lung
      fibroblasts, tropoelastin gene expression was found to be upregulated late in
      gestation. From days 18 to 21 of gestation, there was a 4.5-fold increase in
      tropoelastin hnRNA (P < 0.0001) and a 6-fold increase in mRNA (P = 0.002). After
      birth, tropoelastin expression was downregulated. Signals decreased from fetal
      day 21 to postnatal day 2 for both tropoelastin hnRNA (P = 0. 021) and mRNA (P =
      0.043). Tropoelastin hnRNA decreased further from days 2 to 6 (P = 0.04). Both
      tropoelastin hnRNA and mRNA were again upregulated during alveolarization from
      days 9 to 11, indicating that, once upregulated, transcription of the
      tropoelastin gene is not constant but varies with fetal and postnatal age.
      Exposure to >95% oxygen, when initiated on postnatal day 2 or 3 and continued
      until day 11, significantly diminished the developmental increase in tropoelastin
      hnRNA (P < 0.005) and mRNA (P < 0.05) normally seen on days 9-11, indicating that
      the postnatal upregulation of tropoelastin gene expression is inhibited by
      hyperoxic exposure in the early postnatal period.

PMID- 9609734
TI  - Altered ETB- but not ETA-receptor density and function in sheep airway smooth
      muscle cells in culture.
AB  - The possibility that significant changes in endothelin (ET)A- and ETB-receptor
      density and function occur in airway smooth muscle cells (ASMCs) during cell
      growth and extended cell culture was investigated in sheep tracheal ASMCs. As in
      intact tracheal smooth muscle tissue from this species, early-passage sheep ASMCs
      contained a homogeneous population of ETA receptors. However, growth of ASMCs
      from seeding to postconfluence and repeated passage of ASMCs (6th to 14th
      passages) was associated with a substantial increase in ETB-receptor density,
      with no change in ETA-receptor density. ET-1-induced stimulation of ETB receptors
      increased the intracellular Ca2+ concentration in single ASMCs. Interestingly, a
      2-day period of serum deprivation completely eliminated the increase in ETB
      receptor density and the ETB receptor-mediated change in intracellular Ca2+
      concentration. In summary, growth and repeated passage of sheep ASMCs were
      associated with a profound and selective increase in the density and function of
      the ETB receptor, a receptor subtype not present in early-passage ASMCs and not
      detected in intact sheep tracheal airway smooth muscle.

PMID- 9609735
TI  - Pulmonary surfactant proteins A and D enhance neutrophil uptake of bacteria.
AB  - The collectins are a class of collagenous lectin proteins present in serum and
      pulmonary secretions [pulmonary surfactant protein (SP) A and SP-D] that are
      believed to participate in innate immune responses to various pathogens. With the
      use of flow cytometric and fluorescent-microscopic assays, SP-A and SP-D were
      shown to increase calcium-dependent neutrophil uptake of Escherichia coli,
      Streptococcus pneumoniae, and Staphylococcus aureus. Evidence is provided that
      the collectins enhanced bacterial uptake through a mechanism that involved both
      bacterial aggregation and direct actions on neutrophils. The degree of
      multimerization of SP-D preparations was a critical determinant of both
      aggregating activity and potency in enhancing bacterial uptake. The mechanisms of
      opsonizing activity of SP-D and SP-A differed in important respects from those of
      opsonizing antibodies. These results provide the first evidence that surfactant
      collectins may promote neutrophil-mediated clearance of bacteria in the lung
      independently of opsonizing antibody.

PMID- 9609736
TI  - Acetylcholine stimulates alveolar macrophages to release inflammatory cell
      chemotactic activity.
AB  - Neurological transmitters including ACh, substance P (SP), and calcitonin gene
      related peptide (CGRP) play an important role in regulating airway tone, and
      increased bronchial reactivity to cholinergic stimulation is a well-recognized
      phenomenon in patients with bronchial asthma. We postulated that ACh, SP, and
      CGRP might stimulate alveolar macrophages (AMs) to release neutrophil, monocyte,
      and eosinophil chemotactic activities. To test this hypothesis, bovine AMs were
      isolated by bronchoalveolar lavage and cultured. AMs released chemotactic
      activities in response to ACh in a dose- and time-dependent manner (P < 0.05).
      However, SP and CGRP did not stimulate bovine AMs. Checkerboard analysis revealed
      that these released activities were predominantly chemotactic. Partial
      characterization and molecular-sieve column chromatography revealed that low
      molecular-weight lipid-soluble activity was predominant. Lipoxygenase inhibitors
      significantly blocked the release of chemotactic activities (P < 0.05).
      Leukotriene B4- and platelet-activating factor-receptor antagonists blocked the
      chemotactic activities. Immunoreactive leukotriene B4 significantly increased in
      supernatant fluids in response to ACh (P < 0.05), but platelet-activating factor
      did not. The receptor responsible for the release of the chemotactic activities
      was the muscarinic M3 receptor. These data demonstrate that ACh stimulates AMs to
      release lipoxygenase-derived chemotactic activities and plays a role in
      inflammatory cell recruitment into the airway.

PMID- 9609737
TI  - Regulation of myosin heavy chain gene expression after short-term diaphragm
      inactivation.
AB  - Although prolonged diaphragm denervation (DNV) produces myofiber atrophy and a
      loss of type I myosin heavy chain (MHC) expression, short-term DNV leads to
      significant diaphragm hypertrophy. The purpose of this study was to explore the
      regulation of MHC isoform expression and muscle remodeling during DNV hypertrophy
      of the diaphragm. Both unilateral and bilateral DNV led to similar changes, with
      a significant increase in total RNA content and muscle mass but no change in dry
      to-wet weight ratio. Sarcomere number was also increased in diaphragm myofibers
      after DNV ( approximately 20%), suggesting an adaptive response to muscle
      stretch. There was hypertrophy of type I myofibers and increased coexpression of
      type I and type II MHCs within single myofibers by immunocytochemistry as well as
      increased type I MHC (25-46%) and decreased type IIb MHC (14-39%) by SDS-PAGE.
      Contractility parameters were also consistent with a type II-to-type I MHC
      phenotype transformation. Importantly, DNV-induced modulation of MHC isoform mRNA
      transcript levels did not correspond to changes in their cognate proteins,
      suggesting a major degree of posttranscriptional control. We conclude that DNV
      hypertrophy of the diaphragm is associated with reciprocal changes in type I and
      type II MHC isoforms that are directly opposed to the type I-to-type II MHC
      phenotype transformation reported in the diaphragm DNV atrophy model.
      Furthermore, in contradistinction to most hypertrophy models, control of MHC gene
      expression and myofibrillar remodeling after short-term DNV appears to entail
      major involvement of posttranscriptional regulatory mechanisms.

PMID- 9609738
TI  - Regulation of amiloride-sensitive sodium absorption in murine airway epithelium
      by C-type natriuretic peptide.
AB  - We have previously shown that C-type natriuretic peptide (CNP), a guanylate
      cyclase agonist, can stimulate cystic fibrosis transmembrane conductance
      regulator (CFTR)-mediated chloride secretion in murine airway epithelial cells
      via protein kinase (PK) A activation through the inhibition of cGMP-inhibited
      phosphodiesterases. In this paper, we show that CNP is also capable of reducing
      amiloride-sensitive sodium absorption in murine airway epithelium through a cGMP
      dependent mechanism that is separate from the CFTR regulatory signaling pathway.
      Both murine tracheal and nasal tissues exhibit sensitivity to amiloride-sensitive
      sodium regulation by exogenously added CNP. CNP depolarized the nasal
      transepithelial potential difference by 6.3 +/- 0.5 mV, whereas the cGMP
      inhibited phosphodiesterase inhibitor milrinone actually hyperpolarized the nasal
      transepithelial potential difference by 2.0 +/- 1.2 mV in mice homozygous for a
      CFTR stop mutation [CFTR(-/-)]. Inhibition of guanylate cyclase activity and PKG
      activity in normal mice resulted in an increase in amiloride-sensitive sodium
      absorption, suggesting that tonic regulation of amiloride-sensitive sodium
      absorption is in part due to basal cGMP levels and PKG activity.

PMID- 9609739
TI  - Eosinophils, major basic protein, and polycationic peptides augment bovine airway
      myocyte Ca2+ mobilization.
AB  - Previous studies in vivo or in isolated airway preparations have suggested that
      eosinophil-derived polycationic proteins enhance airway smooth muscle tone in an
      epithelium-dependent manner. We assessed the direct effects of activated human
      eosinophil supernatant, major basic protein (MBP), and polycationic polypeptides
      on basal and agonist-stimulated intracellular Ca2+ concentrations ([Ca2+]i) in
      cultured bovine tracheal smooth muscle (TSM) cells. A 1-h incubation of myocytes
      with activated eosinophil buffer resulted in a doubling of basal [Ca2+]i and
      increased responsivity to histamine compared with myocytes that were exposed to
      sham-activated eosinophil buffer. In addition, concentration-dependent acute
      transient increases and subsequent 1-h sustained elevations of basal [Ca2+]i were
      observed immediately after addition of MBP and model polycationic proteins.
      Finally, both peak and plateau [Ca2+]i responses to bradykinin addition were
      augmented significantly in cultured myocytes that had been exposed to low
      concentrations of MBP or model polycationic proteins but were inhibited at
      greater concentrations. This elevated [Ca2+]i to polycationic proteins was
      manifest in epithelium-denuded bovine TSM strips as concentration-dependent
      increased basal tone. We conclude that activated eosinophil supernatant, MBP, and
      other polycationic proteins have a direct effect on both basal and subsequent
      agonist-elicited Ca2+ mobilization in cultured TSM cells; TSM strips in vitro
      demonstrated, respectively, augmented and diminished responses to the contractile
      agonist acetylcholine. It is possible that alteration in myocyte Ca2+
      mobilization induced by these substances may influence clinical states of altered
      airway tone, such as asthma.

PMID- 9609740
TI  - O3-induced formation of bioactive lipids: estimated surface concentrations and
      lining layer effects.
AB  - Recent evidence suggests that inhaled ozone (O3) does not induce toxicity via
      direct epithelial interactions. Reactions with epithelial lining fluid (ELF)
      constituents limit cellular contact and generate products, including lipid
      ozonation products, postulated to initiate pathophysiological cascades. To
      delineate specific aspects of lipid ozonation product formation and to estimate
      in situ surface concentrations, we studied the O3 absorption characteristics of
      ELF constituent mixtures and measured hexanal, heptanal, and nonanal yields as a
      function of ascorbic acid (AH2) concentration. Exposures of isolated rat lungs,
      bronchoalveolar lavage fluid (BALF) and egg phosphatidylcholine (PC) liposomes
      were conducted. 1) O3 absorption by AH2, uric acid, and albumin exceeded that by
      egg PC and glutathione. O3 reaction with egg PC occurred when AH2 concentrations
      were reduced. 2) Aldehydes were produced in low yield during lung and BALF
      exposures in a time- and O3 concentration-dependent manner. 3) Diminishing BALF
      AH2 content lowered O3 uptake but increased aldehyde yields. Conversely, AH2
      addition to egg PC increased O3 uptake but reduced aldehyde yields. Estimations
      of bioactive ozonation and autoxidation product accumulation within the ELF
      suggested possible nanomolar to low micromolar concentrations. The use of
      reaction products as metrics of O3 exposure may have intrinsic sensitivity and
      specificity limitations. Moreover, due to the heterogenous nature of O3 reactions
      within the ELF, dose-response relationships may not be linear with respect to O3
      absorption.

PMID- 9609742
TI  - cAMP protects endothelial barrier function independent of inhibiting MLC20
      dependent tension development.
AB  - Exposure of cultured human umbilical vein endothelial cells to the cAMP agonists
      theophylline and forskolin decreased constitutive isometric tension of a
      confluent monolayer inoculated on a collagen membrane, but it did not prevent
      increased tension in cells exposed to thrombin. The inability of cAMP agonists to
      prevent tension development correlated with an inability of cAMP stimulation to
      prevent increased 20-kDa myosin light chain (MLC20) phosphorylation in response
      to thrombin. Although cAMP did not prevent tension development or increased MLC20
      phosphorylation, cAMP attenuated the effect of thrombin on transendothelial
      electrical resistance across a confluent monolayer inoculated on a gold
      microelectrode. Activation of cAMP-dependent signal transduction did not prevent
      a decline in resistance in thrombin-treated cells, but it more promptly restored
      transendothelial resistance to initial basal levels (10 min) compared with
      thrombin only (60 min). ML-7, an MLC kinase antagonist, at doses that attenuate
      increased MLC20 phosphorylation and tension development, did not prevent a
      decline in resistance in thrombin-treated cells. Yet, ML-7 also restored
      transendothelial resistance more rapidly than thrombin alone (20 min) but at a
      slower rate than cAMP. These data demonstrate that activation of cAMP-dependent
      signal transduction protects barrier function independent of inhibition of MLC20
      dependent tension development.

PMID- 9609741
TI  - Rhinovirus infection induces mucus hypersecretion.
AB  - Rhinorrhea is a prominent symptom of the common cold. Although increases in
      vascular permeability and serous cell secretion have been demonstrated in human
      nasal mucus during active rhinovirus infections, changes in mucin constituents
      have not been quantified. Nonallergic (n = 48) and asymptomatic allergic rhinitis
      (n = 32) subjects were inoculated with rhinovirus type hanks before the spring
      allergy season. Nasal lavages were performed before inoculation (day 0), then
      daily for 5 days afterward. The subjects were divided into infected and
      noninfected groups on the basis of evidence of successful rhinovirus infection
      (nasal shedding of virus or fourfold increases in specific serum antibodies).
      Concentrations of interleukin (IL)-8, markers of vascular leak (IgG), seromucous
      cells (lysozyme), and mucoglycoprotein exocytosis [7F10-immunoreactive mucin
      (7F10-irm) and Alcian blue staining of acidic mucoglycoproteins] were measured in
      lavage fluids. The infected subgroup had maximal increases in nasal lavage fluid
      concentrations of IL-8 (sevenfold), IgG (fourfold), total protein (twofold), and
      gel-phase 7F10-irm (twofold) on day 3. There were no differences between infected
      allergic and nonallergic subjects. IL-8 and gel-phase 7F10-irm were significantly
      higher in infected than in noninfected subjects. In addition to promoting plasma
      exudation, rhinovirus hanks infection increases IL-8 and gel-phase mucin
      secretion. These processes may contribute to a progression from watery rhinorrhea
      to mucoid discharge, with mild neutrophilic infiltration during the common cold.

PMID- 9609743
TI  - Leukotriene B4 mediates histamine induction of NF-kappaB and IL-8 in human
      bronchial epithelial cells.
AB  - In 16HBE transformed human bronchial epithelial cells, histamine stimulated
      interleukin (IL)-8 mRNA and protein secretion, and this histamine stimulation was
      inhibited by the H1-receptor antagonist diphenhydramine (DPH), by the inhibitor
      of 5-lipoxygenase-activating protein (FLAP) MK-886, by the 5-lipoxygenase
      inhibitor Zileuton, and by dexamethasone. Histamine stimulated bronchial
      epithelial cell production of leukotriene B4 (LTB4), and this production was
      inhibited by FLAP inhibitors MK-886 and L-655,238 and Zileuton. Histamine
      stimulated IL-8 luciferase reporter gene activity that was inhibited with DPH,
      dexamethasone, MK-886 and L-655,238, and Zileuton. The inhibition of IL-8
      transcription and protein secretion by FLAP inhibitors and Zileuton was reversed
      with exogenous LTB4. There was increased IL-8 nuclear factor-kappaB (NF-kappaB)
      DNA-binding activity after histamine stimulation, and this was inhibited by DPH
      and MK-886. Cytoplasmic phospholipase A2 mRNA levels were also potently induced
      by histamine. Thus histamine stimulation of bronchial epithelial cells involves
      binding at H1 receptors, production of LTB4, activation of NF-kappaB and
      increased expression of IL-8.

PMID- 9609744
TI  - Upregulation of urokinase in alveolar macrophages and lung tissue in response to
      silica particles.
AB  - Impaired fibrinolytic activity and persistent fibrin deposits in lung tissue have
      been associated with lung fibrotic disorders. The present study examined the
      sources of plaminogen activator (PA) changes induced by a single intratracheal
      administration of silica particles (5 mg) in the mouse lung. We found in both
      control and silica-treated animals that amiloride almost totally abolished PA
      activity in bronchoalveolar lavage (BAL) fluid (BALF), indicating that initial
      upregulation (from day 1) as well as sustained PA activity (up to day 30)
      observed in response to silica is related to changes in urokinase-type PA (uPA).
      The upregulation of BALF uPA activity was associated with a marked and persistent
      increase in uPA mRNA levels in lung tissue. Changes in uPA expression were also
      reflected in the BAL cell fraction. A maximal and constant increase in cell uPA
      activity was associated with the early response to silica, whereas significant
      but lower upregulation was still noted at the fibrotic stage. From days 3 to 30,
      a progressive increase in uPA mRNA levels was noted in BAL inflammatory cells
      elicited by silica. Because the number of BAL neutrophils was strongly correlated
      with BALF and BAL cell-associated uPA activity, their involvement in uPA
      upregulation was addressed by inducing neutropenia with cyclophosphamide (200
      mg/kg ip) before administration of the silica. Neutrophilic depletion did not,
      however, reduce, and even increased, the BAL cell-associated uPA activity. At the
      BALF level, neutropenia did not change PA activity in silica-treated mice,
      pointing to alveolar macrophages as the principal source of uPA in response to
      silica. Immunohistochemical stainings identified alveolar macrophages and
      pneumocytes as uPA-expressing cells in silica-treated animals (day 30). Intense
      and heterogenous staining was observed in silicotic nodules. These findings
      indicate that urokinase produced by alveolar macrophages is operative not only at
      the alveolitis stage but also later in the fibrotic process, produced by silica
      particles, supporting the role of uPA in fibrogenesis.

PMID- 9609745
TI  - Induction of tenascin in rat lungs undergoing bleomycin-induced pulmonary
      fibrosis.
AB  - Lung injury induced by bleomycin is associated with early inflammation and
      subsequent excessive deposition of extracellular matrix. In the present study, we
      investigated the expression of extracellular matrix glycoprotein tenascin (TN)
      during pulmonary injury induced by bleomycin. After the initial lung injury
      induced by intratracheal bleomycin instillation, TN and collagen type III (COL
      III) mRNAs were greatly induced. The pattern of induction of TN was distinct from
      that of COL III. TN was primarily induced during the early inflammatory phase,
      whereas the increase in COL III synthesis continued during the reparative phase.
      The induction and localization of TN mRNA during bleomycin-induced pulmonary
      injury were also examined by in situ hybridization. TN mRNA was focally induced
      in rat lungs 3 days after bleomycin administration. Induction of TN mRNA was
      spatially restricted in the areas of tissue inflammation. The interstitial cells
      in alveolar septal walls and secondary septal tips in the areas of tissue damage
      were the major source of TN mRNA production. Expression of TN mRNA was decreased
      as the inflammation attenuated and development of fibrosis proceeded.
      Immunocytochemical analyses of TN protein distribution in the lung yielded
      corroborative results. Immunoreactive TN protein was found in a patchy
      distribution in alveolar septal walls and secondary septal tips in the areas of
      damaged tissues. This study demonstrated that TN is a unique early-response
      extracellular matrix component to bleomycin-induced pulmonary injury and is
      induced at the sites of the inflammation, suggesting a potential role of TN as a
      modulator of pulmonary inflammation and repair.

PMID- 9609746
TI  - eNOS expression is not altered in pulmonary vascular remodeling due to increased
      pulmonary blood flow.
AB  - Congenital heart lesions resulting in increased pulmonary blood flow are common
      and if unrepaired often lead to pulmonary hypertension and heart failure.
      Therefore, we hypothesized that increased pulmonary blood flow without changes in
      pressure would result in remodeling of the pulmonary arterial wall. Furthermore,
      because the vasodilator nitric oxide is produced by the lung, is regulated by
      flow in the systemic circulation, and has been associated with the regulation of
      smooth muscle cell proliferation, we hypothesized that increased pulmonary blood
      flow would result in altered expression of endothelial nitric oxide synthase
      (eNOS). To study this hypothesis, 42-day-old Sprague-Dawley rats had creation of
      an aortocaval shunt to increase pulmonary blood flow for 6 wk. The shunt resulted
      in a significant increase in the heart- and lung-to-body weight ratios (>2-fold;
      P < 0.05) without significant alteration of pulmonary or systemic blood
      pressures. Significant thickening of the pulmonary arterial medial wall
      developed, with increased muscularization of small (50-100 micron)- and medium
      (101-200 micron)-sized arteries as evidenced by alpha-actin smooth muscle
      staining. Proliferating cell nuclear antigen staining and bromodeoxyuridine
      labeling did not detect proliferating smooth muscle cells in the vascular wall.
      eNOS Western and Northern blot analyses and immunohistochemical staining
      demonstrated that eNOS protein and mRNA levels were not altered in the shunt
      lungs compared with sham controls. Therefore, increased pulmonary flow without
      increased pressure resulted in pulmonary artery medial thickening, without
      ongoing proliferation. Unlike chronic hypoxia-induced vascular remodeling, the
      pulmonary vascular remodeling resulting from increased pulmonary blood flow is
      not associated with changes in eNOS.

PMID- 9609747
TI  - Modulation of aquaporin 4 and the amiloride-inhibitable sodium channel in
      perinatal rat lung epithelial cells.
AB  - During the perinatal period, a dramatic reversal of lung transepithelial ion and
      water transport occurs that involves the amiloride-inhibitable Na+ channel
      (ENaC). Aquaporin (AQP) water channel proteins facilitate cell membrane water
      transport. We now report that AQP-4, localized to basolateral membranes of airway
      epithelial cells, increases its mRNA expression in developing lung eightfold
      during the 2 days before birth to reach a peak on the first postnatal day in the
      lungs but not in brains or kidneys of neonatal rats. AQP-4 and the alpha-, beta-,
      and gamma-subunits of ENaC are both expressed by cultured rat fetal distal lung
      epithelial (FDLE) cells. AQP-4 and ENaC expression increase in FDLE cells
      cultured on uncoated permeant filters compared with matched control cells
      cultured on filters containing extracellular matrix derived from fetal lung
      epithelial cells. Similarly, AQP-4 expression increases in FDLE cells exposed to
      21% O2 compared with cells exposed to 3% O2. These data demonstrate that AQP-4
      expression is highest on the first day after birth in neonatal rat lungs.
      Exposure to ambient 21% O2 may contribute to increases in AQP-4 and ENaC
      expression to facilitate water transport across neonatal airway epithelia in the
      immediate postnatal period.

PMID- 9609748
TI  - High basal gastric acid secretion in somatostatin receptor subtype 2 knockout
      mice.
AB  - BACKGROUND & AIMS: Somatostatin receptor subtype 2 (sst2) agonists inhibit
      gastric secretion. The role of sst2 in the regulation of acid secretion was
      assessed using sst2 knockout mice and urethane to induce somatostatin release.
      METHODS: Acid secretion was monitored every 10 minutes by gastric perfusion and
      backtitration of perfusates in fasted, urethane-anesthetized C57/129 sst2 (-/-)
      mice and wild-type (+/+) mice. The ileal vein was cannulated for drug injection.
      Intragastric pH and serum gastrin were monitored 1 hour after anesthesia without
      perfusion. RESULTS: Gastric pH values were lower in sst2 (-/-) mice (3.8 +/- 0.3)
      than in wild-type mice (7.1 +/- 0.1, P < 0.05), and there was no difference in
      gastrin levels. Basal acid output per 2 hours was 10-fold higher in sst2 knockout
      mice compared with wild-type mice. The gastrin antibody abolished the high basal
      acid secretion in sst2 (-/-) mice and had no effect in wild-type mice. The
      somatostatin antibody increased basal secretion by 4-fold in wild-type and had no
      effect in knockout mice. Somatostatin 14 or the sst2 agonist DC 32-87 inhibited
      pentagastrin-stimulated acid secretion in wild-type mice, but did not alter basal
      secretion in knockout mice. CONCLUSIONS: These results indicate that sst2 is the
      main subtype whereby endogenous somatostatin suppresses gastric acid secretion
      through inhibition of gastrin action.

PMID- 9609750
TI  - Meniere of Meniere's syndrome.

PMID- 9609749
TI  - A placebo-controlled trial of ICAM-1 antisense oligonucleotide in the treatment
      of Crohn's disease.
AB  - BACKGROUND & AIMS: Intercellular adhesion molecule 1 (ICAM-1) plays an important
      role in the trafficking and activation of leukocytes and is up-regulated in
      inflamed mucosa in Crohn's disease. ISIS 2302 is an antisense phosphorothioate
      oligodeoxynucleotide that inhibits ICAM-1 expression. The aim of this study was
      to obtain preliminary assessment of tolerability, pharmacology, and efficacy of
      ISIS 2302 in Crohn's disease. METHODS: Twenty patients with active, steroid
      treated Crohn's disease were randomized (3:1, ISIS 2302 to placebo) to receive
      over 26 days 13 intravenous infusions of ISIS 2302 (0.5, 1, or 2 mg/kg) or saline
      placebo in a double-blinded study. The patients were followed up for 6 months.
      RESULTS: At the end of treatment. 47% (7 of 15) of ISIS 2302-treated and 20% (1
      of 5) of the placebo-treated patients were in remission (Crohn's Disease Activity
      Index [CDAI] < 150). At the end of month 6, 5 of these 7 ISIS 2302-treated
      remitters were still in remission, and a 6th patient had a CDAI of 156.
      Corticosteroid usage was significantly lower (P = 0.0001) in the ISIS 2302
      treated patients. These findings were corroborated by significant increases in
      beta7 and alpha d bearing CD3+ peripheral blood lymphocytes and by decreases in
      intestinal mucosal ICAM-1 expression during the treatment period. CONCLUSIONS:
      ISIS 2302 seems to be a well-tolerated and promising therapy for steroid-treated
      Crohn's disease.

PMID- 9609751
TI  - Clinical course of colorectal Crohn's disease: a 35-year follow-up study of 507
      patients.
AB  - BACKGROUND & AIMS: Crohn's disease (CD) confined to the colon and rectum is an
      increasing clinical entity. The aim of this study was to assess the features and
      clinical course of colorectal CD. METHODS: This was a retrospective cohort study
      of 507 patients in whom colonic or rectal CD had been diagnosed between 1955 and
      1989. RESULTS: Colonic distribution was segmental in 40%, total in 31%, and left
      sided in 26%. Perianal/rectal fistulas occurred in 37%. In patients who attained
      clinical remission, the 5-year cumulative relapse rate after diagnosis was 67%
      (95% confidence interval [CI], 62-72). At the initial presentation of CD, the
      frequency of major surgery decreased from 24% to 14% (P < 0.005) over time.
      Still, the overall long-term probability of major surgery after 10 years was
      unaltered (49% vs. 47%). The presence of fistulas increased the probability of
      surgical resection (relative risk [RR], 1.7 [95% CI, 1.3-2.2]), whereas left
      sided disease was associated with a decrease (RR, 0.6 [95% CI, 0.4-0.8]). Twenty
      four percent of the patients developed inflammation in the small bowel. The
      cumulative risk for a permanent ileostomy was 25% (95% CI, 21-29) 10 years after
      diagnosis. CONCLUSIONS: Colorectal CD is an increasing entity carrying
      substantial morbidity. Half of the patients will undergo surgical resection
      within the first 10 years, and half of those will ultimately undergo ileostomy.
      Changed management at diagnosis has not affected the long-term probability of
      resection.

PMID- 9609752
TI  - Crohn's disease in Olmsted County, Minnesota, 1940-1993: incidence, prevalence,
      and survival.
AB  - BACKGROUND & AIMS: Many centers worldwide have reported an increased incidence of
      Crohn's disease, but population-based data in North America are sparse. We
      studied the incidence and prevalence of Crohn's disease in Olmsted County,
      Minnesota, and examined temporal trends in incidence and survival. METHODS:
      Residents diagnosed with Crohn's disease between 1970 and 1993 were incidence
      cases, and residents with Crohn's disease who were alive on January 1, 1991, were
      prevalence cases. Cases from previous studies were reconfirmed. Rates were
      adjusted using 1990 U.S. Census figures for whites. Incidence trends were
      evaluated with a Poisson regression model. Survival from diagnosis was compared
      with that expected for U.S. north-central whites. RESULTS: Between 1940 and 1993,
      225 incidence cases were identified, for an adjusted incidence rate of 5.8 per
      100,000 person-years. On January 1, 1991, there were 145 residents with Crohn's
      disease, an adjusted prevalence rate of 133 per 100,000, 46% higher than that
      seen in 1980. Incidence rates before 1964 were significantly lower than those of
      1989-1993. Observed survival was less than expected (P = 0.007). CONCLUSIONS: The
      incidence of Crohn's disease has stabilized since the 1970s at a rate higher than
      that seen previously. Prevalence has increased by 46% since 1980. Overall
      survival is slightly decreased.

PMID- 9609753
TI  - Meta-analysis of the relationship between Helicobacter pylori seropositivity and
      gastric cancer.
AB  - BACKGROUND & AIMS: Reports in the literature regarding the relationship of
      Helicobacter pylori infection to gastric cancer are conflicting. The aim of this
      study was to identify the source of heterogeneity between studies. METHODS: Meta
      analysis of cohort or case-control studies with age- and/or sex-matched controls,
      providing raw data on H. pylori infection detected by serology, was used.
      RESULTS: A fully recursive literature search identified 19 qualified studies with
      2491 patients and 3959 controls. Test for homogeneity found a significant
      difference in odds ratio between patients with early and advanced gastric cancer
      (6.35 vs. 2.13; P = 0.01), patients with cardiac and noncardiac gastric cancer
      (1.23 vs. 3.08; P = 0.003), and population- and hospital-based controls (2.11 vs.
      1.49; P < 0.001). The summary odds ratio for gastric cancer in H. pylori-infected
      patients is 1.92 (95% confidence interval [CI], 1.32-2.78), 2.24 (95% CI, 1.15
      4.4), and 1.81 (95% CI, 1.16-2.84) for all studies, cohort, and case-control
      studies, respectively. H. pylori-infected younger patients have a higher relative
      risk for gastric cancer than older patients with odds ratios decreasing from 9.29
      at age < or = 29 years to 1.05 at age > or = 70 years. H. pylori infection is
      equally associated with the intestinal or diffuse type of gastric cancer.
      CONCLUSIONS: H. pylori infection is a risk factor for gastric cancer. The
      heterogeneity of reported results is caused by differences in the selection of
      controls, patient age, and the site and stage of gastric cancer.

PMID- 9609754
TI  - Allelic loss on chromosome 18q as a prognostic marker in stage II colorectal
      cancer.
AB  - BACKGROUND & AIMS: Loss of heterozygosity (LOH) on chromosome 18q is frequent in
      colorectal cancer (CRC) and has been associated with poor prognosis in stage II
      tumors. This study investigated the frequency of LOH in sporadic CRC and its
      effect on patient prognosis. METHODS: One hundred forty-four patients were
      screened for LOH at 18q by polymerase chain reaction using three polymorphic
      microsatellite markers. RESULTS: Nineteen patients were excluded because their
      tumors showed microsatellite instability in at least one marker. Of the remaining
      125 patients, 121 were informative in at least one marker; 45% (54 of 121) showed
      18q LOH. Five-year survival was 42% in those with 18q LOH and 73% in those
      without 18q LOH (P = 0.008). Multivariate analysis showed that tumor side (P =
      0.0001) and 18q LOH (P = 0.01) were the only independent prognostic factors.
      Examining markers individually showed that only the lost of D18S474 had a
      significant influence on survival in patients with stage II CRC (P = 0.016).
      CONCLUSIONS: 18q LOH indicates an unfavorable outcome in patients with stage II
      CRC. Our results emphasize the importance of the 18q21.1 region, where several
      tumor-suppressor genes have been mapped. Microsatellite analysis may be useful in
      identifying high-risk patients who might benefit from adjuvant therapy.

PMID- 9609755
TI  - Prognostic significance of allelic lost at chromosome 18q21 for stage II
      colorectal cancer.
AB  - BACKGROUND & AIMS: Allelic loss of a portion of chromosome 18q and lack of
      expression of deleted in colorectal cancer (DCC) protein has been reported as an
      adverse prognostic indicator for stage II (i.e., Dukes' B2) colorectal cancer.
      Our aim was to assess whether the DCC gene locus was responsible. METHODS: We
      amplified five DNA microsatellite markers located on chromosome 18q21 surrounding
      or within the DCC gene locus, including a DCC intragenic (TA)n microsatellite,
      from DNA microdissected and isolated from paraffin-embedded, formalin-fixed
      specimens of 70 patients with stage II colorectal cancer. Epidemiological and
      survival data were blinded from the microsatellite analysis to avoid bias.
      RESULTS: The average follow-up time was 63.3 months for all patients. Eleven
      patients died of colorectal cancer by the end of the study. Loss of
      heterozygosity of 18q21 was present in 30 of 70 (43%) tumors. After adjustment
      for all other evaluated factors, 18q21 allelic loss was not a predictor of
      survival (hazard ratio, 1.17; 95% confidence interval, 0.27-5.10; P = 0.84).
      CONCLUSIONS: Loss of heterozygosity of 18q21 does not seem to predict a survival
      disadvantage in stage II colorectal cancer in our patient population, and its
      proposed use as a prognosticator of survival or chemotherapy stratification
      marker for stage II tumors is not substantiated.

PMID- 9609756
TI  - Abnormal expression of CD44 variants in the exfoliated cells in the feces of
      patients with colorectal cancer.
AB  - BACKGROUND & AIMS: Recent investigations have shown that CD44 variant exons are
      frequently overexpressed in human colorectal adenocarcinoma. The aim of this
      study was to investigate abnormal expression of the CD44 gene in exfoliated cells
      from patients with colorectal cancer. METHODS: Exfoliated cells in feces from 25
      patients with colorectal cancer before and after surgery and from 15 healthy
      volunteers were analyzed. CD44 standard, variant 6, and variant 10 messenger RNA
      (mRNA) expressions were examined in the exfoliated cells in feces by using
      reverse-transcription polymerase chain reaction followed by Southern
      hybridization with exon-specific probes. RESULTS: CD44 standard mRNA was detected
      in all samples before and after surgery and in all healthy volunteers. CD44
      variant 6 and variant 10 mRNA were detected in 17 of 25 patients (68%) and 15 of
      25 patients (60%), respectively, in individual feces obtained before surgery.
      CD44 variant 6 mRNA and variant 10 mRNA were detected in postoperative samples in
      3 of 25 patients (12%) and 7 of 25 patients (28%), respectively. Fifteen of 17
      patients who were positive for CD44v6 based on preoperative fecal samples became
      negative after surgery (88.2%). Similarly, 12 of 15 patients who were CD44v10
      positive in preoperative fecal samples were negative postoperatively (80%).
      CONCLUSIONS: These results suggest that analysis of CD44 variant expression in
      the exfoliated cells in feces can provide a noninvasive diagnostic test for
      colorectal cancer.

PMID- 9609757
TI  - Tylosis esophageal cancer locus on chromosome 17q25.1 is commonly deleted in
      sporadic human esophageal cancer.
AB  - BACKGROUND & AIMS: Tumor-suppressor genes found in inherited cancer
      predisposition syndromes are also responsible for sporadic cancers of the same
      type. Recently, the tylosis oesophageal cancer (TOC) gene locus has been mapped
      to 17q25 by linkage analyses of pedigrees with focal nonepidermolytic
      palmoplantar keratoderma associated with a high risk of esophageal cancer
      development. The aim of this study was to clarify whether the TOC locus is
      affected in sporadic esophageal cancers. METHODS: We investigated loss of
      heterozygosity (LOH) on 17q in 58 sporadic esophageal squamous cell carcinomas
      (ESCs) using 20 microsatellite markers focusing on the TOC locus. RESULTS: LOH on
      17q was observed in 37 of 52 (71%) informative cases at one or more loci, 80%
      (33/37) of which included the TOC locus. The smallest common deleted region was
      at D17S1839 within the TOC locus. CONCLUSIONS: The constructed deletion map
      revealed that the TOC locus is commonly deleted in sporadic ESCs, suggesting that
      a tumor-suppressor gene responsible for ESC is contained within this locus.

PMID- 9609758
TI  - Expression of transforming growth factor beta receptors in normal human colon and
      sporadic adenocarcinomas.
AB  - BACKGROUND & AIMS: An absence or a presence of mutated transforming growth factor
      (TGF)-beta receptors is a possible hypothesis explaining the resistance of cancer
      cells to the growth-inhibitory effect of TGF-beta. Mutations involving
      microsatellite-like regions of the type II TGF-beta receptor have been described
      in subgroups of colorectal cancers. The aim of this study was to investigate the
      expression and distribution of TGF-beta receptors in sporadic colorectal cancers
      and normal tissues. METHODS: Thirty-three sporadic colorectal cancers and 20
      normal colonic tissues were explored by immunohistochemistry for the expression
      of type I and type II TGF-beta receptors. Eighteen tumor and 20 normal samples
      were used for radioactive thermocycling and sequencing of the two microsatellite
      like regions of the type II receptor. RESULTS: Both receptors were overexpressed
      in tumors compared with normal samples. There was a relationship between the
      abundance of type II receptor expression and the degree of differentiation of the
      tumors but not the Dukes' staging or the localization of the neoplasias. No
      mutation was observed in the microsatellite-like regions of receptor II in any of
      the samples. CONCLUSIONS: Sporadic colorectal cancers do not show an absence or a
      presence of mutated TGF-beta receptors that could explain a resistance to TGF
      beta-mediated growth inhibition. The pathways to tumorigenesis of sporadic
      colorectal cancers may be different from those of some hereditary ones.

PMID- 9609759
TI  - Differential activation of IGF-II promoters P3 and P4 in Caco-2 cells during
      growth and differentiation.
AB  - BACKGROUND & AIMS: Insulin-like growth factor (IGF)-II gene is overexpressed in
      colon cancers. Transcriptional up-regulation may be the major mechanism
      contributing to its overexpression. IGF-II messenger RNA (mRNA) levels are up
      regulated during proliferation followed by a significant decline during
      differentiation of Caco-2 cells. Mechanisms underlying transcriptional regulation
      of the IGF-II gene promoters (P1-P4) have yet to be examined in colon cancers,
      which was the basis for this study. METHODS: Ribonuclease protection assay was
      used to measure IGF-II mRNA derived from P1-P4. To determine if changes in the
      IGF-II transcripts reflected differences in promoter activity, transient
      transfection assays with the full-length P1-P4-luciferase expression vectors were
      performed. RESULTS: Both P3- and P4-derived transcripts were significantly up
      regulated during the proliferative phase of the cells (days 3-6 in culture) and
      declined rapidly in cells undergoing differentiation (days 7-10); conversely, P1-
      and P2-derived transcripts were not detected. Similarly, transcriptional activity
      of P3 and P4 promoters reached peak levels by days 4-6 and declined rapidly
      thereafter. P1 and P2 were relatively inactive on all days. CONCLUSIONS: The
      activity of the P3 and P4 promoters may play a selective role in regulating IGF
      II mRNA levels during growth and differentiation of colon cancer cells.

PMID- 9609760
TI  - The genetically programmed down-regulation of lactase in children.
AB  - BACKGROUND & AIMS: Intestinal lactase activity is high in all healthy human
      babies, but in adults a genetic polymorphism, which acts in cis to the lactase
      gene, determines high or low messenger RNA (mRNA) expression and activity
      (lactase persistence and nonpersistence, respectively). Our aim was to
      investigate the onset of expression of this polymorphism in children. METHODS:
      Activities were analyzed in relation to age in normal biopsy specimens from a 20
      year collection of diagnostic specimens. In a smaller set of 32 samples, aged 2
      132 months, RNA was extracted for semiquantitative reverse-transcription
      polymerase chain reaction. Marker polymorphisms were used to determine the
      allelic origin of lactase mRNA transcripts. RESULTS: Analysis of 866 children
      showed evidence that the lactase persistence/nonpersistence polymorphism began
      before 5 years of age. The 32 children tested had high lactase mRNA and activity.
      Six children aged 2-16 months showed equal expression of two alleles, 2 children
      aged 7 and 14 months showed slightly asymmetric expression, and 7 children aged
      22-132 months showed very asymmetric expression, the second allele being
      undetectable in the 11-year-old, as previously seen in lactase-persistent
      heterozygote adults. CONCLUSIONS: Genetically programmed down-regulation of the
      lactase gene is detectable in children from the second year of life, although the
      onset and extent are somewhat variable.

PMID- 9609761
TI  - Interleukin 15 activity in the rectal mucosa of inflammatory bowel disease.
AB  - BACKGROUND & AIMS: Interleukin (IL)-15 has been found to share many
      immunoregulatory activities in lymphocytes with IL-2. The aim of this study was
      to investigate IL-15 activity in organ cultures, localization of IL-15 messenger
      RNA (mRNA), and proliferation of lamina propria mononuclear cells (LPMCs) in
      response to recombinant IL-15 using the mucosal tissues obtained from patients
      with inflammatory bowel disease (IBD). METHODS: The contents of IL-15, tumor
      necrosis factor alpha, and IL-2 in the culture supernatant of the rectal mucosal
      tissues were determined by an enzyme-linked immunosorbent assay. Expression of IL
      15 mRNA was analyzed by in situ hybridization, and proliferative response of
      LPMCs to recombinant IL-15 was determined by [3H]thymidine incorporation into
      DNA. RESULTS: Significantly greater IL-15 activity was detected in active IBD,
      and this elevation was also observed in inactive ulcerative colitis. In contrast,
      greater tumor necrosis factor alpha activity was observed only in active IBD, and
      IL-2 was not detected in organ cultures. In situ hybridization showed IL-15 mRNA
      in macrophages and epithelial cells in active IBD specimens, and recombinant IL
      15 induced a dose-dependent proliferative response in LPMCs. CONCLUSIONS: Mucosal
      IL-15 may be involved in the pathogenesis of IBD as one of the important
      mediators in activation of mucosal immune cells.

PMID- 9609762
TI  - Proinflammatory cytokines differentially modulate their own expression in human
      intestinal mucosal mesenchymal cells.
AB  - BACKGROUND & AIMS: Intestinal homeostasis is coordinated through the response of
      different cell types, including the interaction of immune with nonimmune cells.
      This study investigated the effect of immune cell-derived proinflammatory
      cytokines on mesenchymal cell proliferation and gene product expression. METHODS:
      Primary cultures of human mucosal mesenchymal cells were activated with
      interleukin (IL)-1 beta, IL-6, and tumor necrosis factor alpha (TNF-alpha).
      Proliferation was measured by thymidine incorporation, messenger RNA (mRNA)
      expression was assessed by Northern blot analysis, and IL-1 receptor type was
      identified by reverse-transcription polymerase chain reaction. RESULTS:
      Mesenchymal cells dose-dependently proliferated in response to IL-1 beta, IL-6,
      and TNF-alpha. Each cytokine differentially induced mRNA expression in a dose
      dependent and selective fashion: IL-1 beta was the most potent inducer, TNF-alpha
      was weaker, and IL-6 induced little or no mRNA; in contrast, IL-6 mRNA was the
      most abundantly induced, followed by IL-1 beta mRNA, whereas TNF-alpha mRNA was
      weakly and infrequently expressed. The IL-1 receptor antagonist inhibited
      cytokine mRNA expression, and mesenchymal cells expressed the type II, but not
      the type I, IL-1 receptor. CONCLUSIONS: The ability of intestinal mesenchymal
      cells to express proinflammatory gene products implicates them as regulators of
      local immune cells through immune-nonimmune interactions. Thus, mesenchymal cells
      should be considered as active regulators of intestinal immunity under normal and
      inflammatory conditions.

PMID- 9609763
TI  - Levamisole inhibits intestinal Cl- secretion via basolateral K+ channel blockade.
AB  - BACKGROUND & AIMS: Phenylimidazothiazoles have recently been shown to activate
      wild-type and mutant cystic fibrosis transmembrane conductance regulator (CFTR)
      Cl- channels in transfected cells and were proposed as therapy for cystic
      fibrosis. The aim of this study was to investigate the effects of
      phenylimidazothiazoles on regulated transepithelial Cl- transport in intact
      epithelia. METHODS: T84 intestinal epithelial cells grown on permeable supports
      and stripped human colonic mucosal sheets were studied by conventional current
      voltage clamping. Selective permeabilization of apical or basolateral membranes
      with the monovalent ionophore nystatin was used to isolate basolateral K+ and
      apical Cl- channel activity, respectively. 86Rb+ uptake was assessed for Na/K/2Cl
      cotransporter and Na+,K(+)-adenosine triphosphatase activity. RESULTS: In T84
      monolayers and human colon, levamisole and its brominated derivative
      bromotetramisole failed to activate transepithelial secretion. In fact, these
      compounds dose-dependently inhibited secretory responses to the cyclic adenosine
      monophosphate agonist forskolin and the Ca2+ agonist carbachol. In permeabilized
      T84 monolayers, phenylimidazothiazoles weakly activated apical Cl- currents
      (consistent with their reported action on CFTR) and did not affect bumetanide
      sensitive or bumetanide-insensitive 86+Rb+ uptake. Instead, they profoundly
      inhibited the basolateral Ba(2+)-sensitive and Ba(2+)-insensitive K+ currents.
      CONCLUSIONS: Phenylimidazothiazoles block K+ channels required for Cl(-)
      secretory responses elicited by diverse pathways in model epithelia and native
      colon, an effect that outweighs their ability to activate apical Cl- channels.

PMID- 9609764
TI  - Solitarial premotor neuron projections to the rat esophagus and pharynx:
      implications for control of swallowing.
AB  - BACKGROUND & AIMS: The buccopharyngeal and esophageal phases of swallowing are
      controlled by distinct networks of premotor neurons localized in the nucleus
      tractus solitarius. The neuronal circuitry coordinating the two phases was
      investigated using a combination of central and peripheral tracing techniques.
      METHODS: Using pseudorabies virus, a transsynaptic tracer, in anesthetized rats,
      third-order esophageal neurons (neurons projecting to premotor neurons) were
      identified. In a separate protocol that combined transsynaptic and retrograde
      fluorescent tracing, third-order esophageal neurons projecting to pharyngeal
      motoneurons (buccopharyngeal premotor neurons) were then identified. RESULTS:
      Third-order esophageal neurons were identified in the interstitial and
      intermediate subnuclei of the nucleus tractus solitarius and in other medullary,
      pontine, midbrain, and forebrain nuclei. A subpopulation of these neurons (double
      labeled) in the interstitial and intermediate subnuclei were found to project to
      pharyngeal motoneurons (buccopharyngeal premotor neurons) and to be linked
      synaptically to esophageal premotor neurons. CONCLUSIONS: The synaptic link
      between buccopharyngeal and esophageal premotor neurons provides an anatomic
      pathway for the central initiation of esophageal peristalsis and its coordination
      with the pharyngeal phase of swallowing. This neural circuitry within the nucleus
      tractus solitarius is consistent with a complex central control mechanism for the
      swallowing motor sequence that can function independently of afferent feedback.

PMID- 9609765
TI  - Prostaglandin E2 and aggressive factors increase the gland luminal pressure in
      the rat gastric mucosa in vivo.
AB  - BACKGROUND & AIMS: The gastroprotective properties of prostaglandins in low
      concentrations are still unclear. In this study, we investigated the effects of
      prostaglandin E2 (PGE2), indomethacin, and intraluminally applied HCl or ethanol
      on intraglandular pressure, mucus thickness, acid secretion, and gastric mucosal
      blood flow. METHODS: Glandular pressure and mucous gel thickness were measured
      with microelectrodes during intravital microscopy in thiobutabarbital sodium
      anesthetized rats. Gastric blood flow was measured with laser Doppler flowmetry.
      RESULTS: In pentagastrin-treated rats, glandular pressure increased significantly
      in response to topical (1 micrograms/mL) or intra-arterial (12 micrograms.kg-1.h
      1) PGE2 from approximately 17 to 69 and 18 to 57 mm Hg, respectively, whereas
      blood flow, mucus thickness, and acid secretion were unaltered. Indomethacin (3
      mg/kg intravenously) significantly decreased glandular pressure from
      approximately 20 to 11 mm Hg. Intraluminal application of 10 and 100 mmol/L HCl
      or 20% and 40% ethanol significantly increased glandular pressure but had no
      effect after indomethacin pretreatment. CONCLUSIONS: Endogenous PGE2 is important
      for maintaining a high glandular pressure, and exogenous PGE2 potently increases
      glandular pressure at concentrations not altering blood flow, mucus thickness, or
      acid secretion. This suggests that high intraglandular pressures might be
      involved in gastroprotection.

PMID- 9609766
TI  - Overexpression of pp60c-src elicits invasive behavior in rat colon epithelial
      cells.
AB  - BACKGROUND & AIMS: Src activation is reported as an early event found in
      preneoplastic colonic adenomas and in 70% of colon carcinomas. The aim of this
      study was to identify the biological consequences of c-src overexpression in rat
      colon epithelial cells. METHODS: Introduction and overexpression of c-src in an
      immortalized rat colon epithelial cell line was achieved using lipofection.
      Transfectants were tested for changes in growth and cell behavior using different
      in vitro assay systems. RESULTS: Colon epithelial cells overexpressing c-src
      showed the ability to form microcolonies in soft agar without acquiring
      tumorigenic potential. In in vitro assays, c-src transfectants displayed a gain
      of invasive potential through Matrigel without an accompanying change in
      migrational ability. No discernible qualitative changes were observed in the
      phosphotyrosyl protein profile between c-src and v-src transfectants. Assessment
      of the cadherin/catenin status in these cells revealed an intact, functional
      complex with no detectable tyrosine phosphorylation of different components of
      the complex. CONCLUSIONS: Overexpression of c-src in an immortalized rat colon
      epithelial cell line does not elicit full neoplastic transformation but enhances
      anchorage-independent growth and confers invasion capability. Increased invasion
      through Matrigel was not linked to inactivation of the cadherin complex in c-src
      transfectants.

PMID- 9609767
TI  - Clinical events after transjugular intrahepatic portosystemic shunt: correlation
      with hemodynamic findings.
AB  - BACKGROUND & AIMS: Transjugular intrahepatic portosystemic shunt (TIPS)
      procedures are increasingly being used, but the relationship between the
      hemodynamic effects of TIPS and the clinical events on follow-up remains
      undefined. Hence, we have investigated the hemodynamic correlations of portal
      hypertension-related events after a TIPS procedure. METHODS: Prospective follow
      up of 122 cirrhotic patients who had a TIPS procedure performed because of
      variceal hemorrhage was conducted. RESULTS: The portacaval pressure gradient
      (PPG) significantly decreased after the TIPS procedure (from 19.7 +/- 4.6 to 8.6
      +/- 2.7 mm Hg; P > 0.001), but increased thereafter and at rebleeding (n = 25)
      was > 12 mm Hg in all patients (18.4 +/- 4.6 mm Hg). Twenty-six patients
      developed ascites; the PPG (measured in 19) was always > 12 mm Hg. Increasing the
      PPG to > 12 mm Hg occurred very frequently (83% at 1 year). Within 1 year, 77% of
      patients underwent balloon angioplasty or restenting. However, 80% had again a
      PPG of > 12 mm Hg 1 year after reintervention. Hepatic encephalopathy developed
      in 31% of patients at 1 year; 21 of 23 patients had a PPG of < 12 mm Hg.
      CONCLUSIONS: Total protection from the risk of recurrent complications of portal
      hypertension after a TIPS procedure requires that the PPG be decreased and
      maintained < 12 mm Hg. However, reintervention will be required in most patients
      within 1 year and again the second year. On the other hand, such portal
      decompression is associated with an increased risk of hepatic encephalopathy.

PMID- 9609768
TI  - Targeted inhibition of hepatitis C virus-directed gene expression in human
      hepatoma cell lines.
AB  - BACKGROUND & AIMS: The 5'-nontranslated region (NTR) of hepatitis C virus (HCV)
      contains important elements that control HCV translation. The aim of this study
      was to determine whether antisense oligonucleotides against the NTR of the HCV
      genome can be targeted to inhibit HCV gene expression. METHODS: Antisense
      oligonucleotides directed against a sequence in the internal ribosomal binding
      site of the NTR (anti-III) and a portion of the NTR overlapping the core protein
      translational start site of HCV (anti-IV) were prepared. In transient
      transfections of a plasmid containing a luciferase gene immediately downstream
      from an HCV NTR insert, oligonucleotides anti-III and anti-IV in the form of
      asialoglycoprotein-polylysine complexes were administered to Huh7 cells, and
      luciferase activity generated by cytomegalovirus (CMV) HCVluc was measured.
      RESULTS: Anti-III inhibited luciferase activity by 75% and 99% at 0.01 mumol/L
      and 0.1 mumol/L, respectively. Similarly, anti-IV inhibited luciferase activity
      88% and 99% at 0.01 mumol/L and 0.1 mumol/L, respectively. In cell lines stably
      transfected with CMV HCVluc plasmid, complexed anti-III inhibited luciferase
      activity in Huh7 cells by 20% at 10 mumol/L and 85% at 60 mumol/L, and was
      competable by an excess of asialoglycoprotein. CONCLUSIONS: Antisense
      oligonucleotides that bind to the NTR of HCV can be targeted by receptor-mediated
      endocytosis, and they specifically inhibit HCV-directed protein synthesis under
      intracellular conditions.

PMID- 9609769
TI  - Successful treatment of retractile mesenteritis with oral progesterone.
AB  - Retractile mesenteritis is a rare inflammatory mesenteric disorder that involves
      the intestine secondarily. The natural history of this process is diverse, but
      most patients require some empiric therapeutic measures. Up to now,
      pharmacological therapy has included corticosteroids, colchicine, and
      immunosuppressive drugs. Although these drugs are successful in most patients,
      some have been refractory to these therapies and, in others, the beneficial
      effects were counterbalanced by adverse reactions. Many patients require surgery,
      but most have poor results. This report describes a 42-year-old man with
      histologically proven retractile mesenteritis refractory to surgical intervention
      who had a good response to oral progesterone (10 mg/day for 6 months) with
      complete disappearance of tumor mass and clinical symptoms. No adverse effects
      were detected. Current knowledge about the mechanism by which progesterone
      affects fibrogenesis is scanty. It seems likely that progesterone down-regulates
      proliferation and metabolism of fibroblasts and fibrogenesis.

PMID- 9609770
TI  - An evidence-based approach to gastroenterology therapy. Evidence-Based
      Gastroenterology Steering Group.

PMID- 9609771
TI  - Presentation of the Julius M Friedenwald Medal to Eugene D Jacobson, M.D.

PMID- 9609772
TI  - Invited editorial on "Effect of arterial occlusion on responses of group III and
      IV afferents to dynamic exercise".

PMID- 9609773
TI  - Effect of arterial occlusion on responses of group III and IV afferents to
      dynamic exercise.
AB  - Our laboratory has shown previously that a low level of dynamic exercise induced
      by electrical stimulation of the mesencephalic locomotor region (MLR) stimulated
      group III and IV muscle afferents in decerebrate unanesthetized cats (C. M.
      Adreani, J. M. Hill, and M. P. Kaufman. J. Appl. Physiol. 83: 1811-1817, 1997).
      In the present study, we have extended these findings by examining the effect of
      occluding the arterial supply to the dynamically exercising muscles on the
      afferents' responses to MLR stimulation. In decerebrate cats, we found that
      arterial occlusion increased the responsiveness to a low level of dynamic
      exercise in 44% of the group III and 47% of the group IV afferents tested.
      Occlusion, compared with the freely perfused state, did not increase the
      concentrations of either hydrogen ion or lactate ion in the venous effluent from
      the exercising muscles. We conclude that arterial occlusion caused some
      unspecified substance to accumulate in the working muscles to increase the
      sensitivity of equal percentages of group III and IV afferents to dynamic
      exercise.

PMID- 9609774
TI  - Regional deposition of inhaled particles in human lungs: comparison between men
      and women.
AB  - We measured detailed regional deposition patterns of inhaled particles in healthy
      adult male (n = 11; 25 +/- 4 yr of age) and female (n = 11; 25 +/- 3 yr of age)
      subjects by means of a serial bolus aerosol delivery technique for monodisperse
      fine [particle diameter (Dp) = 1 micron] and coarse aerosols (Dp = 3 and 5
      micron). The bolus aerosol (40 ml half-width) was delivered to a specific
      volumetric depth (Vp) of the lung ranging from 100 to 500 ml with a 50-ml
      increment, and local deposition fraction (LDF) was assessed for each of the 10
      local volumetric regions. In all subjects, the deposition distribution pattern
      was very uneven with respect to Vp, showing characteristic unimodal curves with
      respect to particle size and flow rate. However, the unevenness was more
      pronounced in women. LDF tended to be greater in all regions of the lung in women
      than in men for Dp = 1 micron. For Dp = 3 and 5 micron, LDF showed a marked
      enhancement in the shallow region of Vp </= 200 ml in women compared with men (P
      < 0.05). LDF in women was comparable to or smaller than those of men in deep lung
      regions of Vp > 200 ml. Total lung deposition was comparable between men and
      women for fine particles but was consistently greater in women than men for
      coarse particles regardless of flow rates used: the difference ranged from 9 to
      31% and was greater with higher flow rates (P < 0.05). The results indicate that
      1) particle deposition characteristics differ between healthy men and women under
      controlled breathing conditions and 2) deposition in women is greater than that
      in men.

PMID- 9609775
TI  - Effect of continuous negative-pressure breathing on skin blood flow during
      exercise in a hot environment.
AB  - To assess the impact of continuous negative-pressure breathing (CNPB) on the
      regulation of skin blood flow, we measured forearm blood flow (FBF) by venous
      occlusion plethysmography and laser-Doppler flow (LDF) at the anterior chest
      during exercise in a hot environment (ambient temperature = 30 degreesC, relative
      humidity = approximately 30%). Seven male subjects exercised in the upright
      position at an intensity of 60% peak oxygen consumption rate for 40 min with and
      without CNPB after 20 min of exercise. The esophageal temperature (Tes) in both
      conditions increased to 38.1 degreesC by the end of exercise, without any
      significant differences between the two trials. Mean arterial pressure (MAP)
      increased by approximately 15 mmHg by 8 min of exercise, without any significant
      difference between the two trials before CNPB. However, CNPB reduced MAP by
      approximately 10 mmHg after 24 min of exercise (P < 0.05). The increase in FBF
      and LDF in the control condition leveled off after 18 min of exercise above a Tes
      of 37.7 degreesC, whereas in the CNPB trial the increase continued, with a rise
      in Tes despite the decrease in MAP. These results suggest that CNPB enhances
      vasodilation of skin above a Tes of approximately 38 degrees C by stretching
      intrathoracic baroreceptors such as cardiopulmonary baroreceptors.

PMID- 9609776
TI  - Effects of high-intensity intermittent swimming on glucose transport in rat
      epitrochlearis muscle.
AB  - Recently (K. Kawanaka, I. Tabata, and M. Higuchi. J. Appl. Physiol. 83: 429-433,
      1997), we demonstrated that glucose transport activity after repeated 10-s-long
      in vitro tetani in rat epitrochlearis (Epi) muscle was negatively correlated with
      the postcontraction muscle glycogen concentration. Therefore, we examined whether
      high-intensity intermittent swimming, which depletes muscle glycogen to a lower
      level than that observed after ten 10-s-long in vitro tetani, elicits higher
      glucose transport than that observed after ten 10-s-long in vitro tetani, which
      has been regarded as the exercise-induced maximal stimulus for glucose transport.
      In male rats, 2-deoxy-D-glucose transport rate in Epi muscle after eight bouts of
      high-intensity intermittent swimming with a weight equal to 18% of body mass
      (exercise duration: 20 s, rest duration between exercise bouts: 40 s) was higher
      than that observed after the ten 10-s-long tetani (2.25 +/- 0.08 vs. 1.02 +/-
      0.16 micromol . ml intracellular water-1 . 20 min-1). Muscle glycogen
      concentration in Epi after eight bouts of high-intensity intermittent swimming
      was significantly lower than that observed after ten 10-s-long in vitro tetani
      (7.6 +/- 0.5 vs. 14.8 +/- 1.4 micromol glucose/g muscle). These observations show
      that the high-intensity intermittent swimming increases glucose transport in rat
      Epi to a much higher level than that induced by ten 10-s-long in vitro tetani,
      which has been regarded as the exercise-related maximal stimulus for glucose
      transport. Furthermore, this finding suggests that the lower muscle glycogen
      level after high-intensity intermittent swimming than after in vitro tetani may
      play a role, because there was a significant negative correlation between glucose
      transport and muscle glycogen concentration in Epi after high-intensity swimming
      and in vitro tetani.

PMID- 9609777
TI  - Hyperhydration: tolerance and cardiovascular effects during uncompensable
      exercise-heat stress.
AB  - This study examined the efficacy of glycerol and water hyperhydration (1 h before
      exercise) on tolerance and cardiovascular strain during uncompensable exercise
      heat stress. The approach was to determine whether 1-h preexercise hyperhydration
      (29.1 ml H2O/kg lean body mass with or without 1.2 g/kg lean body mass of
      glycerol) provided a physiological advantage over euhydration. Eight heat
      acclimated men completed three trials (control euhydration before exercise, and
      glycerol and water hyperhydrations) consisting of treadmill exercise-heat stress
      (ratio of evaporative heat loss required to maximal capacity of climate = 416).
      During exercise ( approximately 55% maximal O2 uptake), there was no difference
      between glycerol and water hyperhydration methods for increasing (P < 0.05) total
      body water. Glycerol hyperhydration endurance time (33. 8 +/- 3.0 min) was longer
      (P < 0.05) than for control (29.5 +/- 3.5 min), but was not different (P > 0.05)
      from that of water hyperhydration (31.3 +/- 3.1 min). Hyperhydration did not
      alter (P > 0.05) core temperature, whole body sweating rate, cardiac output,
      blood pressure, total peripheral resistance, or core temperature tolerance.
      Exhaustion from heat strain occurred at similar core and skin temperatures and
      heart rates in each trial. Symptoms at exhaustion included syncope and ataxia,
      fatigue, dyspnea, and muscle cramps (n = 11, 10, 2, and 1 cases, respectively).
      We conclude that 1-h preexercise glycerol hyperhydration provides no meaningful
      physiological advantage over water hyperhydration and that hyperhydration per se
      only provides the advantage (over euhydration) of delaying hypohydration during
      uncompensble exercise-heat stress.

PMID- 9609778
TI  - Recovery of muscle transfers replacing the total plantar flexor muscle group in
      rats.
AB  - In rats, combinations of plantar flexor muscles representing approximately 20,
      40, 60, and 80% of the mass of the total plantar flexor group were transferred
      orthotopically in the absence of synergistic muscles and allowed to recover for
      120 days. We hypothesized that, compared with their individual control values for
      structural and functional variables, the transfers would display a hierarchical
      array of deficits, proportional to their initial mass and, consequently,
      inversely proportional to the relative load on the transfers. Surprisingly,
      compared with their individual control values, each muscle transfer displayed
      deficits of 30-40% in muscle mass, total fiber cross-sectional area, and maximum
      isometric force, with the exception of the smallest transfer, the plantaris (PLN)
      muscle, which recovered 100% of its control value for each of these variables.
      Therefore, except for the PLN transfer, the muscle transfers studied displayed
      deficits similar in magnitude to those reported for muscles transferred in the
      presence of synergistic muscles. The greater recovery of the PLN transfer was
      attributed to the relatively large requirement for force production imposed on
      this transfer due to the average force requirements of the total plantar flexor
      group.

PMID- 9609779
TI  - Smaller lungs in women affect exercise hyperpnea.
AB  - We subjected 29 healthy young women (age: 27 +/- 1 yr) with a wide range of
      fitness levels [maximal oxygen uptake (VO2 max): 57 +/- 6 ml . kg-1 . min-1; 35
      70 ml . kg-1 . min-1] to a progressive treadmill running test. Our subjects had
      significantly smaller lung volumes and lower maximal expiratory flow rates,
      irrespective of fitness level, compared with predicted values for age- and height
      matched men. The higher maximal workload in highly fit (VO2 max > 57 ml . kg-1 .
      min-1, n = 14) vs. less-fit (VO2 max < 56 ml . kg-1 . min-1, n = 15) women caused
      a higher maximal ventilation (VE) with increased tidal volume (VT) and breathing
      frequency (fb) at comparable maximal VT/vital capacity (VC). More expiratory flow
      limitation (EFL; 22 +/- 4% of VT) was also observed during heavy exercise in
      highly fit vs. less-fit women, causing higher end-expiratory and end-inspiratory
      lung volumes and greater usage of their maximum available ventilatory reserves.
      HeO2 (79% He-21% O2) vs. room air exercise trials were compared (with screens
      added to equalize external apparatus resistance). HeO2 increased maximal
      expiratory flow rates (20-38%) throughout the range of VC, which significantly
      reduced EFL during heavy exercise. When EFL was reduced with HeO2, VT, fb, and VE
      (+16 +/- 2 l/min) were significantly increased during maximal exercise. However,
      in the absence of EFL (during room air exercise), HeO2 had no effect on VE. We
      conclude that smaller lung volumes and maximal flow rates for women in general,
      and especially highly fit women, caused increased prevalence of EFL during heavy
      exercise, a relative hyperinflation, an increased reliance on fb, and a greater
      encroachment on the ventilatory "reserve." Consequently, VT and VE are
      mechanically constrained during maximal exercise in many fit women because the
      demand for high expiratory flow rates encroaches on the airways' maximum flow
      volume envelope.

PMID- 9609780
TI  - Bioenergetics of contracting skeletal muscle after partial reduction of blood
      flow.
AB  - The purpose of this study was to examine the bioenergetics and regulation of O2
      uptake (VO2) and force production in contracting muscle when blood flow was
      moderately reduced during a steady-state contractile period. Canine gastrocnemius
      muscle (n = 5) was isolated, and 3-min stimulation periods of isometric, tetanic
      contractions were elicited sequentially at rates of 0.25, 0.33, and 0.5
      contractions/s (Hz) immediately followed by a reduction of blood flow [ischemic
      (I) condition] to 46 +/- 3% of the value obtained at 0.5 Hz with normal blood
      flow. The VO2 of the contracting muscle was significantly (P < 0.05) reduced
      during the I condition [6.5 +/- 0.8 (SE) ml . 100 g-1 . min-1] compared with the
      same stimulation frequency with normal flow (11.2 +/- 1.5 ml . 100 g-1 . min-1),
      as was the tension-time index (79 +/- 12 vs. 123 +/- 22 N . g-1 . min-1,
      respectively). The ratio of VO2 to tension-time index remained constant
      throughout all contraction periods. Muscle phosphocreatine concentration, ATP
      concentration, and lactate efflux were not significantly different during the I
      condition compared with the 0. 5-Hz condition with normal blood flow. However, at
      comparable rates of VO2 and tension-time index, muscle phosphocreatine
      concentration and ATP concentration were significantly less during the I
      condition compared with normal-flow conditions. These results demonstrate that,
      in this highly oxidative muscle, the normal balance of O2 supply to force output
      was maintained during moderate ischemia by downregulation of force production. In
      addition, 1) the minimal disruption in intracellular homeostasis after the
      initiation of ischemia was likely a result of steady-state metabolic conditions
      having already been activated, and 2) the difference in intracellular conditions
      at comparable rates of VO2 and tension-time index between the normal flow and I
      condition may have been due to altered intracellular O2 tension.

PMID- 9609781
TI  - Hypohydration effects on skeletal muscle performance and metabolism: a 31P-MRS
      study.
AB  - The purpose of this study was to determine whether hypohydration reduces skeletal
      muscle endurance and whether increased H+ and Pi might contribute to performance
      degradation. Ten physically active volunteers (age 21-40 yr) performed supine
      single-leg, knee-extension exercise to exhaustion in a 1.5-T whole body magnetic
      resonance spectroscopy (MRS) system when euhydrated and when hypohydrated (4%
      body wt). 31P spectra were collected at a rate of one per second at rest,
      exercise, and recovery, and were grouped and averaged to represent 10-s
      intervals. The desired hydration level was achieved by having the subjects
      perform 2-3 h of exercise in a warm room (40 degrees C dry bulb, 20% relative
      humidity) with or without fluid replacement 3-8 h before the experiment. Time to
      fatigue was reduced (P < 0.05) by 15% when the subjects were hypohydrated [213 +/
      12 vs. 251 +/- 15 (SE) s]. Muscle strength was generally not affected by
      hypohydration. Muscle pH and Pi/beta-ATP ratio were similar during exercise and
      at exhaustion, regardless of hydration state. The time constants for
      phosphocreatine recovery were also similar between trials. In summary, moderate
      hypohydration reduces muscle endurance, and neither H+ nor Pi concentration
      appears to be related to these reductions.

PMID- 9609782
TI  - Postprandial lipemia in endurance-trained people during a short interruption to
      training.
AB  - This study examined changes in postprandial lipemia in endurance-trained people
      during a short interruption to training. Nine men and one woman (ages 18-55 yr)
      undertook fat tolerance tests after 15 h, 60 h, and 6.5 days without exercise.
      The test meal (1.2 g fat, 1.1 g carbohydrate, 66 kJ/kg body mass) was consumed
      after a 12-h fast. Postprandial lipemia increased rapidly with detraining (area
      under plasma triacylglycerol vs. time curve: 8.42 +/- 1.40, 11. 35 +/- 1.38, and
      11.97 mM x 6 h at 15 h, 60 h and 6.5 days, respectively). In the fasted state,
      plasma triacylglycerol concentration (0.85 +/- 0.15, 1.09 +/- 0.12, and 1.10 +/-
      0.11 mM at 15 h, 60 h and 6.5 days, respectively) and the ratio of total
      cholesterol to high-density-lipoprotein cholesterol increased with detraining.
      Values were significantly higher at 60 h and 6.5 days than values at 15 h ( P <
      0.05) for each of these three variables. The serum insulin response was higher (
      P < 0.05) at 6.5 days than at 15 h (81.6 +/- 11.3, 87.6 +/- 11.4, and 94.5 +/-
      9.4 microIU/ml x 6 h at 15 h, 60 h, and 6.5 days, respectively). Frequent
      exercise is needed to maintain a low level of postprandial lipemia and
      insulinemia in trained people.

PMID- 9609783
TI  - L-NAME does not affect exercise-induced pulmonary hypertension in thoroughbred
      horses.
AB  - The present study was carried out to examine the effects of nitric oxide synthase
      inhibition with Nomega-nitro-L-arginine methyl ester (L-NAME) on the right atrial
      as well as on the pulmonary arterial, capillary, and venous blood pressures of
      horses during rest and exercise performed at maximal heart rate (HRmax).
      Experiments were carried out on seven healthy, sound, exercise-trained
      Thoroughbred horses. Using catheter-tip manometers, with signals referenced at
      the point of the shoulder, we determined phasic and mean right atrial and
      pulmonary vascular pressures in two sets of experiments [control (no medications)
      and L-NAME (20 mg/kg iv given 10 min before exercise studies)]. The studies were
      carried out in random order 7 days apart. Measurements were made at rest and
      during treadmill exercise performed on a 5% uphill grade at 6, 8, and 14.2 m/s.
      Exercise on a 5% uphill grade at 14.2 m/s elicited HRmax and could not be
      sustained for >90 s. In quietly standing horses, L-NAME administration caused a
      significant rise in right atrial, as well as pulmonary arterial, capillary, and
      venous pressures. This indicates that nitric oxide synthase inhibition modifies
      the basal pulmonary vasomotor tone. In both treatments, exercise caused
      progressive significant increments in right atrial and pulmonary vascular
      pressures, but the values recorded in the L-NAME study were not different from
      those in the control study. The extent of exercise-induced tachycardia was
      significantly decreased in the L-NAME study at 6 and 8 m/s but not at 14.2 m/s.
      Thus, L-NAME administration may not modify the equine pulmonary vascular tone
      during exercise at HRmax. However, as indicated by a significant reduction in
      heart rate, L-NAME seems to modify the sympathoneurohumoral response to
      submaximal exercise.

PMID- 9609784
TI  - Mechanical and metabolic determination of VO2 and fatigue during repetitive
      isometric contractions in situ.
AB  - Repetitive isometric tetanic contractions (1/s) of the canine gastrocnemius
      plantaris muscle were studied either at optimal length (Lo) or short length (Ls;
      approximately 0.9 . Lo), to determine the effects of initial length on mechanical
      and metabolic performance in situ. Respective averages of mechanical and
      metabolic variables were (Lo vs. Ls, all P < 0.05) passive tension (preload) = 55
      vs. 6 g/g, maximal active tetanic tension (Po) = 544 vs. 174 (0.38 . Po) g/g,
      maximal blood flow (Q) = 2.0 vs. 1.4 ml . min-1 . g-1, and maximal oxygen uptake
      (VO2) = 12 vs. 9 micromol . min-1 . g-1. Tension at Lo decreased to 0.64 . Po
      over 20 min of repetitive contractions, demonstrating fatigue; there were no
      significant changes in tension at Ls. In separate muscles contracting at Lo, Q
      was set to that measured at Ls (1.1 ml . min-1 . g-1), resulting in decreased VO2
      (7 micromol . min-1 . g-1), and rapid fatigue, to 0.44 . Po. These data
      demonstrate that 1) muscles at Lo have higher Q and VO2 values than those at Ls;
      2) fatigue occurs at Lo with high VO2, adjusting metabolic demand (tension
      output) to match supply; and 3) the lack of fatigue at Ls with lower tension, Q,
      and VO2 suggests adequate matching of metabolic demand, set low by short muscle
      length, with supply optimized by low preload. These differences in tension and
      VO2 between Lo and Ls groups indicate that muscles contracting isometrically at
      initial lengths shorter than Lo are working under submaximal conditions.

PMID- 9609785
TI  - Influence of carbohydrate status on immune responses before and after endurance
      exercise.
AB  - To determine the effect of carbohydrate (CHO) status on immune responses after
      long-duration exercise, on two occasions, 10 men completed a glycogen-depleting
      bout of cycle ergometry followed by 48 h of either a high-CHO diet (HiCHO; 8.0 g
      CHO/kg) or a low-CHO diet (LoCHO; 0.5 g CHO/kg). After the 48 h, subjects
      completed a 60-min ride at 75% maximal O2 uptake (EX). Blood samples were taken
      predepletion, pre-EX, post-EX, and 2 and 24 h post-EX and were assayed for
      leukocyte number and function, glucose, glutamine, and cortisol. The glucose
      responses were significantly higher in the HiCHO (4.62 +/- 0.26 mM) vs. the LoCHO
      (3.19 +/- 0.15 mM) condition post-EX, and glutamine was significantly higher in
      the HiCHO (0.472 +/- 0.036 mM) vs. the LoCHO (0.410 +/- 0.025 mM) condition
      throughout. Cortisol levels were significantly greater in the LoCHO (587 +/- 50
      nM) vs. the HiCHO (515 +/- 62 nM) condition throughout the trial. Lymphocyte
      proliferation (phytohemagglutinin) was significantly depressed after exercise.
      However, there was no difference between conditions, and the depression was not
      correlated with elevations in cortisol. Circulating numbers of leukocytes,
      neutrophils, lymphocytes, and lymphocyte subsets were significantly greater in
      the LoCHO vs. the HiCHO condition at the post-EX and 2 h post-EX time points.
      These data indicate that the exercise and diet manipulation altered the number of
      circulating leukocytes but did not affect the decrease in lymphocyte
      proliferation that occurred after exercise.

PMID- 9609786
TI  - Arousal and ventilatory responses during sleep in children with obstructive sleep
      apnea.
AB  - Abnormal central regulation of upper airway muscles may contribute to the
      pathophysiology of the childhood obstructive sleep apnea syndrome (OSAS). We
      hypothesized that this was secondary to global abnormalities of ventilatory
      control during sleep. We therefore compared the response to chemical stimuli
      during sleep between prepubertal children with OSAS and controls. Patients with
      OSAS aroused at a higher PCO2 (58 +/- 2 vs. 60 +/- 5 Torr, P < 0.05); those with
      the highest apnea index had the highest arousal threshold (r = 0.52, P < 0.05).
      The hypercapnic arousal threshold decreased after treatment. For all subjects,
      hypoxia was a poor stimulus to arousal, whereas hypercapnia and, particularly,
      hypoxic hypercapnia were potent stimuli to arousal. Hypercapnia resulted in
      decreased airway obstruction in OSAS. Ventilatory responses were similar between
      patients with OSAS and controls; however, the sample size was small. We conclude
      that children with OSAS have slightly blunted arousal responses to hypercapnia.
      However, the overall ventilatory and arousal responses are normal in children
      with OSAS, indicating that a global deficit in respiratory drive is not a major
      factor in the etiology of childhood OSAS. Nevertheless, subtle abnormalities in
      ventilatory control may exist.

PMID- 9609787
TI  - Single soleus muscle fiber function after hindlimb unweighting in adult and aged
      rats.
AB  - This investigation compared how hindlimb unweighting (HU) affected the
      contractile function of single soleus muscle fibers from 12- and 30-mo-old
      Fischer 344 Brown Norway F1 Hybrid rats. After 1 wk of HU, functional properties
      of single permeabilized fibers were studied, and, subsequently, the fiber type
      was established by myosin heavy chain (MHC) analysis. After HU, the relative mass
      of soleus declined by 12 and 19% and the relative mass of the gastrocnemius
      declined by 15 and 13% in 12- and 30-mo-old animals, respectively. In 12-mo-old
      animals, the peak active force (5.0 +/- 0.2 x10(-4) vs. 3.8 +/- 0.2 x10(-4) N)
      and the peak specific tension (92 +/- 4 vs. 78 +/- 3 kN/m2) were significantly
      reduced in the MHC type I fibers by 24 and 15%, respectively. In 30-mo-old
      animals, the peak active force declined by 40% (4.7 +/- 0.2 x10(-4) vs. 2.8 +/-
      0. 3 x10(-4) N) and the peak specific tension declined by 30% (79 +/- 5 vs. 55 +/
      4 kN/m2). The maximal unloaded shortening velocity of the MHC type I fibers
      increased in 12-mo-old animals (from 1.65 +/- 0.12 to 2.59 +/- 0.26 fiber
      lengths/s) and in 30-mo-old animals (from 0.90 +/- 0. 09 to 1.50 +/- 0.10 fiber
      lengths/s) after HU. Collectively, these data suggest that the effects of HU on
      single soleus skeletal muscle fiber function occur in both age groups; however,
      the single MHC type I fibers from the older animals show greater changes than do
      single MHC type I fibers from younger animals.

PMID- 9609788
TI  - Alternate activity in the synergistic muscles during prolonged low-level
      contractions.
AB  - The purpose of this study was to investigate the functional interrelationship
      between synergistic muscle activities during low-level fatiguing contractions.
      Six human subjects performed static and dynamic contractions at an ankle joint
      angle of 110 degrees plantar flexion and within the range of 90-110 degrees
      (anatomic position = 90 degrees) under constant load (10% maximal voluntary
      contraction) for 210 min. Surface electromyogram records from lateral
      gastrocnemius (LG), medial gastrocnemius (MG), and soleus (Sol) muscles showed
      high and silent activities alternately in the three muscles and a complementary
      and alternate activity between muscles in the time course. In the second half of
      all exercise times, the number of changes in activity increased significantly (P
      < 0.05) in each muscle. The ratios of active to silent periods of electromyogram
      activity were significantly higher (P < 0.05) in MG (4.5 +/- 2.2) and Sol (4.3 +/
      2.8) than in the LG (0.4 +/- 0.1), but no significant differences were observed
      between MG and Sol. These results suggest that the relative activation of
      synergistic motor pools are not constant during a low-level fatiguing task.

PMID- 9609789
TI  - Enhanced muscle glucose uptake facilitates nitrogen efflux from exercised muscle.
AB  - The hypothesis that glucose ingestion in the postexercise state enhances the
      synthesis of glutamine and alanine in the skeletal muscle was tested. Glucose was
      infused intraduodenally for 150 min (44.5 micromol . kg-1 . min-1) beginning 30
      min after a 150-min period of exercise (n = 7) or an equivalent duration
      sedentary period (n = 10) in 18-h-fasted dogs. Prior exercise caused a twofold
      greater increase in limb glucose uptake during the intraduodenal glucose infusion
      compared with uptake in sedentary dogs. Arterial glutamine levels fell gradually
      with the glucose load in both groups. Net hindlimb glutamine efflux increased in
      response to intraduodenal glucose in exercised but not sedentary dogs (P < 0. 05
      0.01). Arterial alanine levels, depleted by 50% with exercise, rose with
      intraduodenal glucose in exercised but not sedentary dogs (P < 0.05-0.01). Net
      hindlimb alanine efflux also rose in exercised dogs in response to intraduodenal
      glucose (P < 0.05-0.01), whereas it was not different from baseline in sedentary
      controls for the first 90 min of glucose infusion. Beyond this point, it, too,
      rose significantly. We conclude that oral glucose may facilitate recovery of
      muscle from prolonged exercise by enhancing the removal of nitrogen in the form
      of glutamine and alanine.

PMID- 9609790
TI  - Antioxidants protect rat diaphragmatic muscle function under hypoxic conditions.
AB  - In hypoxia, mitochondrial respiration is decreased, thereby leading to a buildup
      of reducing equivalents that cannot be transferred to O2 at the cytochrome
      oxidase. This condition, called reductive stress, can paradoxically lead to
      enhanced formation of reactive O2 species, or a decrease in the ability of the
      cell to defend against an oxidative stress. We hypothesized that antioxidants
      would protect tissues under conditions of hypoxia. Rat diaphragm strips were
      incubated in tissue baths containing one of four antioxidants: N-acetyl-L
      cysteine, dimethyl sulfoxide, superoxide dismutase, or Tiron. The strips were
      directly stimulated in an electrical field. Force-frequency relationships were
      studied under baseline oxygenation (95% O2-5% CO2), after 30 min of hypoxia (95%
      N2-5% CO2), and 30 min after reoxygenation. In all tissues, antioxidants markedly
      attenuated the loss of contractile function during hypoxia (P < 0.01) and also
      significantly improved recovery on reoxygenation (P < 0.05). We conclude that
      both intracellular and extracellular antioxidants improve skeletal muscle
      contractile function in hypoxia and facilitate recovery during reoxygenation in
      an in vitro system. The strong influence of antioxidants during hypoxic exposure
      suggests that they can be as effective in protecting cell function in a reducing
      environment as they have been in oxidizing environments.

PMID- 9609791
TI  - Cellular adaptations of skeletal muscles to cyclosporine.
AB  - The aim of this study was to evaluate the cellular response of the diaphragm,
      extensor digitorum longus (EDL), and soleus (Sol) muscles to clinically relevant
      doses of cyclosporine administered to male rats over 4 wk. Control rats were
      provided with vehicle only. Muscle fiber types, cross-sectional areas, indexes of
      capillarity, and succinate dehydrogenase (SDH) activity were determined by
      quantitative histochemistry. Myosin heavy chain isoforms were identified by SDS
      PAGE, and their proportions were measured by scanning densitometry. Serum
      cyclosporine level, 20-24 h after the last dose of cyclosporine, was 145 +/- 81
      ng/ml. Final body weight and muscle mass were similar between the cyclosporine
      and control groups. In the diaphragm, EDL, and Sol, no differences were observed
      between the groups with regard to fiber type proportions, fiber cross-sectional
      areas, and proportions of myosin heavy chain isoforms. In the EDL, reductions,
      both in SDH activity in type I, IIx, and IIb fibers (-26 to -37%) and in indexes
      of capillarity (-18 to -37%), were noted. In the Sol, SDH activity and
      capillarity were similar between the groups. In the diaphragm of cyclosporine
      treated rats, there was significant reduction in the number of capillaries around
      individual fibers (-5%), whereas levels of SDH activity tended to be lower. This
      suggests that activation history may in part determine muscle-specific responses
      to cyclosporine. We speculate that reduced oxidative activity and capillarity of
      some limb muscles contribute to reduced exercise capacity and the "deconditioned
      state" observed in patients receiving cyclosporine after successful solid-organ
      transplantation.

PMID- 9609792
TI  - Leg intramuscular pressures during locomotion in humans.
AB  - To assess the usefulness of intramuscular pressure (IMP) measurement for studying
      muscle function during gait, IMP was recorded in the soleus and tibialis anterior
      muscles of 10 volunteers during treadmill walking and running by using transducer
      tipped catheters. Soleus IMP exhibited single peaks during late-stance phase of
      walking [181 +/- 69 (SE) mmHg] and running (269 +/- 95 mmHg). Tibialis anterior
      IMP showed a biphasic response, with the largest peak (90 +/- 15 mmHg during
      walking and 151 +/- 25 mmHg during running) occurring shortly after heel strike.
      IMP magnitude increased with gait speed in both muscles. Linear regression of
      soleus IMP against ankle joint torque obtained by a dynamometer produced linear
      relationships (n = 2, r = 0.97 for both). Application of these relationships to
      IMP data yielded estimated peak soleus moment contributions of 0.95-1.65 N . m/kg
      during walking, and 1.43-2.70 N . m/kg during running. Phasic elevations of IMP
      during exercise are probably generated by local muscle tissue deformations due to
      muscle force development. Thus profiles of IMP provide a direct, reproducible
      index of muscle function during locomotion in humans.

PMID- 9609793
TI  - Protein kinase C modulation of ventilatory response to hypoxia in nucleus tractus
      solitarii of conscious rats.
AB  - This study aimed to determine the role of protein kinase C (PKC) in signal
      transduction mechanisms underlying ventilatory regulation in the nucleus tractus
      solitarii (NTS). Microinjection of phorbol 12-myristate 13-acetate into the
      commissural NTS of nine chronically instrumented, unrestrained rats elicited
      significant cardiorespiratory enhancements that lasted for at least 4 h, whereas
      administration of vehicle (n = 15) or the inactive phorbol ester 4alpha-phorbol
      12,13-didecanoate (n = 7) did not elicit minute ventilation (VE) changes. Peak
      hypoxic VE responses (10% O2-balance N2) were measured in 19 additional animals
      after NTS microinjection of bisindolylmaleimide (BIM) I, a selective PKC
      inhibitor (n = 12), BIM V (inactive analog; n = 7), or vehicle (Con; n = 19). In
      Con, VE increased from 139 +/- 9 to 285 +/- 26 ml/min in room air and hypoxia,
      respectively, and similar responses occurred after BIM V. BIM I did not affect
      room air VE but markedly attenuated hypoxia-induced VE increases (128 +/- 12 to
      167 +/- 18 ml/min; P < 0. 02 vs. Con and BIM V). When BIM I was microinjected
      into the cerebellum (n = 4), cortex (n = 4), or spinal cord (n = 4), VE responses
      were similar to Con. Western blots of subcellular fractions of dorsocaudal brain
      stem lysates revealed translocation of PKCalpha, beta, gamma, delta, epsilon, and
      iota isoenzymes during acute hypoxia, and enhanced overall PKC activity was
      confirmed in the particulate fraction of dorsocaudal brain stem lysates harvested
      after acute hypoxia. These studies suggest that, in the adult rat, PKC activation
      in the NTS mediates essential components of the acute hypoxic ventilatory
      response.

PMID- 9609794
TI  - Pyridoxalated hemoglobin polyoxyethylene conjugate reverses hyperdynamic
      circulation in septic sheep.
AB  - We investigated the effects of modified hemoglobin on regional blood flow and
      function of different organs during hyperdynamic sepsis. Fourteen sheep were
      surgically prepared for the study. After a 5-day recovery period, a continuous
      infusion of live Pseudomonas aeruginosa bacteria was begun and maintained for 48
      h. At 24 h, after a hyperdynamic circulation had developed, the animals were
      randomly assigned to two groups: 1) a treatment group (n = 7) that received an
      infusion with 100 mg/kg pyridoxalated hemoglobin polyoxyethylene conjugate (PHP)
      over 30 min and 2) a control group (n = 7) that received only the vehicle. PHP
      infusion increased mean arterial pressure from 86 +/- 2.8 to 101.8 +/- 3.5 mmHg
      (P < 0.05) and systemic vascular resistance index from 769 +/- 42.1 to 1,087 +/-
      56.8 dyn . s . m2 . cm-5 (P < 0.05). PHP infusion did not decrease regional blood
      flow, measured with fluorescent microspheres, below the baseline values in any of
      the analyzed tissues. None of the investigated blood chemistry variables showed
      any changes indicative of impaired organ function after PHP infusion. In our
      model of ovine sepsis we found no side effects after PHP infusion that would
      limit the use of PHP as a nitric oxide scavenger in sepsis.

PMID- 9609795
TI  - Qualitative aspects of exertional dyspnea in patients with interstitial lung
      disease.
AB  - We compared qualitative and quantitative aspects of perceived exertional dyspnea
      in patients with interstitial lung disease (ILD) and normal subjects and sought a
      physiological rationale for their differences. Twelve patients with ILD [forced
      vital capacity = 64 +/- 4 (SE) %predicted] and 12 age-matched normal subjects
      performed symptom-limited incremental cycle exercise tests with measurements of
      dyspnea intensity (Borg scale), ventilation, breathing pattern, operational lung
      volumes, and esophageal pressures (Pes). Qualitative descriptors of dyspnea were
      selected at exercise cessation. Both groups described increased "work and/or
      effort" and "heaviness" of breathing; only patients with ILD described
      "unsatisfied inspiratory effort" (75%), "increased inspiratory difficulty" (67%),
      and "rapid breathing" (58%) (P < 0.05 patients with ILD vs. normal subjects).
      Borg-O2 uptake (VO2) and Borg-ventilation slopes were significantly greater
      during exercise in patients with ILD (P < 0.01). At peak exercise, when dyspnea
      intensity and inspiratory effort (Pes-to-maximal inspiratory pressure ratio) were
      similar, the distinct qualitative perceptions of dyspnea in patients with ILD
      were attributed to differences in dynamic ventilatory mechancis, i.e., reduced
      inspiratory capacity, heightened Pes-to-tidal volume ratio, and tachypnea.
      Factors contributing to dyspnea intensity in both groups were also different: the
      best correlate of the Borg-VO2 slope in patients with ILD was the resting tidal
      volume-to-inspiratory capacity ratio (r = 0.58, P < 0.05) and in normal subjects
      was the slope of Pes-to-maximal inspiratory pressure ratio over VO2 (r = 0.60, P
      < 0. 05).

PMID- 9609796
TI  - Redistribution of pulmonary blood flow during unilateral hypoxia in prone and
      supine dogs.
AB  - We used fluorescent-labeled microspheres in pentobarbital-anesthetized dogs to
      study the effects of unilateral alveolar hypoxia on the pulmonary blood flow
      distribution. The left lung was ventilated with inspired O2 fraction of 1.0,
      0.09, or 0.03 in random order; the right lung was ventilated with inspired O2
      fraction of 1.0. The lungs were removed, cleared of blood, dried at total lung
      capacity, then cubed to obtain approximately 1,500 small pieces of lung (
      approximately 1.7 cm3). The coefficient of variation of flow increased (P <
      0.001) in the hypoxic lung but was unchanged in the hyperoxic lung. Most (70-80%)
      variance in flow in the hyperoxic lung was attributable to structure, in contrast
      to only 30-40% of the variance in flow in the hypoxic lung (P < 0.001). When
      adjusted for the change in total flow to each lung, 90-95% of the variance in the
      hyperoxic lung was attributable to structure compared with 70-80% in the hypoxic
      lung (P < 0.001). The hilar-to-peripheral gradient, adjusted for change in total
      flow, decreased in the hypoxic lung (P = 0.005) but did not change in the
      hyperoxic lung. We conclude that hypoxic vasoconstriction alters the regional
      distribution of flow in the hypoxic, but not in the hyperoxic, lung.

PMID- 9609797
TI  - Ventrolateral medullary respiratory network and a model of cough motor pattern
      generation.
AB  - The primary hypothesis of this study was that the cough motor pattern is
      produced, at least in part, by the medullary respiratory neuronal network in
      response to inputs from "cough" and pulmonary stretch receptor relay neurons in
      the nucleus tractus solitarii. Computer simulations of a distributed network
      model with proposed connections from the nucleus tractus solitarii to
      ventrolateral medullary respiratory neurons produced coughlike inspiratory and
      expiratory motor patterns. Predicted responses of various "types" of neurons (I
      DRIVER, I-AUG, I-DEC, E-AUG, and E-DEC) derived from the simulations were tested
      in vivo. Parallel and sequential responses of functionally characterized
      respiratory-modulated neurons were monitored during fictive cough in decerebrate,
      paralyzed, ventilated cats. Coughlike patterns in phrenic and lumbar nerves were
      elicited by mechanical stimulation of the intrathoracic trachea. Altered
      discharge patterns were measured in most types of respiratory neurons during
      fictive cough. The results supported many of the specific predictions of our
      cough generation model and suggested several revisions. The two main conclusions
      were as follows: 1) The Botzinger/rostral ventral respiratory group neurons
      implicated in the generation of the eupneic pattern of breathing also participate
      in the configuration of the cough motor pattern. 2) This altered activity of
      Botzinger/rostral ventral respiratory group neurons is transmitted to phrenic,
      intercostal, and abdominal motoneurons via the same bulbospinal neurons that
      provide descending drive during eupnea.

PMID- 9609798
TI  - Effects of isometric training on skeletal myosin heavy chain expression.
AB  - This study tested the hypothesis that an isometric resistance-training program
      induces upregulation of slow myosin heavy chain (MHC) expression in a fast-twitch
      skeletal muscle. Thus we studied the effects of two resistance-training programs
      on rodent medial gastrocnemius (MG) muscle that were designed to elicit
      repetitive isometric contractions (10-12 per set; 4 sets per session) of
      different duration (8 vs. 5 s) and activation frequency (100 vs. 60 Hz) per
      contraction during each training session (total of 6 and 12 sessions). Results
      showed that both training paradigms produced significant increases in muscle
      weight ( approximately 11-13%) after completion of training (P < 0.05).
      Significant transformations in MHC expression occurred and involved specifically
      a decrease in the relative expression of the fast type IIb MHC and concomitant
      increased expression of the fast type IIx MHC. These adaptations were observed in
      both the "white" and "red" regions of the MG, and they occurred at both the mRNA
      and protein levels. These adaptations were detected after only six training
      sessions. Neither of the training programs produced any change in the relative
      expression of either the slow type I MHC or the moderately fast type IIa MHC,
      which can be upregulated in the red MG by chronic functional overload. These
      findings show that the isometric protocols used in this investigation were not
      sufficient to induce the hypothesized changes in the myosin heavy chain isoform
      expression in rodent skeletal muscle.

PMID- 9609799
TI  - Hydration effects on physiological strain of horses during exercise-heat stress.
AB  - This study examined the effects of hyperhydration, exercise-induced dehydration,
      and oral fluid replacement on physiological strain of horses during exercise-heat
      stress. On three occasions, six horses completed a 90-min exercise protocol (50%
      maximal O2 uptake, 34.5 degrees C, 48% relative humidity) divided into two 45-min
      periods (exercise I and exercise II) with a 15-min recovery between exercise
      bouts. In random order, horses received no fluid (NF), 10 liters of water (W), or
      a carbohydrate-electrolyte solution (CE) 2 h before exercise and between exercise
      bouts. Compared with NF, preexercise hyperhydration (W and CE) did not alter
      heart rate, cardiac output (Q), stroke volume (SV), core body temperature,
      sweating rate (SR), or sweating sensitivity during exercise I. In contrast, after
      exercise II, exercise-induced dehydration in NF (decrease in body mass: NF, 5.6
      +/- 0.8%; W, 1.1 +/- 0.4%; CE, 1.0 +/- 0.2%) resulted in greater heat storage,
      with core body temperature approximately 1. 0 degrees C higher compared with W
      and CE. In exercise II, the greater thermal strain in NF was associated with
      significant (P < 0. 05) decreases in Q (10 +/- 2%), SV (9 +/- 3%), SR, and
      sweating sensitivity. We concluded that 1) preexercise hyperhydration provided no
      thermoregulatory advantage; 2) maintenance of euhydration by oral fluid
      replacement ( approximately 85% of sweat fluid loss) during exercise in the heat
      was reflected in higher Q, SV, and SR with decreased heat storage; and 3) W or an
      isotonic CE solution was equally effective in reducing physiological strain
      associated with exercise-induced dehydration and heat stress.

PMID- 9609800
TI  - Force, speed, and oxygen consumption in thoroughbred and draft horses.
AB  - Thoroughbred (TB) and draft horses (DH) have long been selected for tasks of very
      different intensities and force-speed relationships. To study their adaptations,
      we measured O2 consumption and related variables in three TB and four DH during
      progressive exercise tests on a level treadmill. The horses exerted a draft force
      of 0, 5, 10, 15, or 20% of their body weight at speeds that increased by 2 m/s
      every 3 min until they could not maintain that speed. We found that TB could
      exert the same draft forces as DH and, at each force, TB achieved about twice the
      speed, twice the external power, and twice the O2 consumption as DH; thus the two
      breeds had the same gross efficiencies. We also found maximal O2 consumption of
      TB to be about twice that of DH (134 vs. 72 ml . kg-1 . min-1, respectively),
      suggesting adaptations to high-intensity exercise. Peak efficiency was reached at
      lower speeds in DH than in TB, suggesting adaptations to high-force, low-speed
      exercise. These differences between TB and DH in force-speed and aerobic
      capacities and in speed for peak efficiency likely reflect different contraction
      velocities in locomotor muscles.

PMID- 9609801
TI  - Chest wall mechanics in sustained microgravity.
AB  - We assessed the effects of sustained weightlessness on chest wall mechanics in
      five astronauts who were studied before, during, and after the 10-day Spacelab D
      2 mission (n = 3) and the 180-day Euromir-95 mission (n = 2). We measured flow
      and pressure at the mouth and rib cage and abdominal volumes during resting
      breathing and during a relaxation maneuver from midinspiratory capacity to
      functional residual capacity. Microgravity produced marked and consistent changes
      (Delta) in the contribution of the abdomen to tidal volume [DeltaVab/(DeltaVab +
      DeltaVrc), where Vab is abdominal volume and Vrc is rib cage volume], which
      increased from 30.7 +/- 3. 5 (SE)% at 1 G head-to-foot acceleration to 58.3 +/-
      5.7% at 0 G head-to-foot acceleration (P < 0.005). Values of DeltaVab/(DeltaVab +
      DeltaVrc) did not change significantly during the 180 days of the Euromir
      mission, but in the two subjects DeltaVab/(DeltaVab + DeltaVrc) was greater on
      postflight day 1 than on subsequent postflight days or preflight. In the two
      subjects who produced satisfactory relaxation maneuvers, the slope of the Konno
      Mead plot decreased in microgravity; this decrease was entirely accounted for by
      an increase in abdominal compliance because rib cage compliance did not change.
      These alterations are similar to those previously reported during short periods
      of weightlessness inside aircrafts flying parabolic trajectories. They are also
      qualitatively similar to those observed on going from upright to supine posture;
      however, in contrast to microgravity, such postural change reduces rib cage
      compliance.

PMID- 9609802
TI  - Role of reaction resistance in limiting carbon monoxide uptake in rabbit lungs.
AB  - The contribution of reaction resistance to overall resistance to pulmonary carbon
      monoxide (CO) uptake [DLCO/(ThetaCO . Vc), where DLCO is lung CO diffusing
      capacity, ThetaCO is CO uptake conductance of erythrocytes, and Vc is pulmonary
      capillary blood volume] was determined in 10 anesthetized, paralyzed, and
      artificially ventilated rabbits. On the basis of the classical double-reciprocal
      equation of F. G. W. Roughton and R. E. Forster (J. Appl. Physiol. 11: 290-302,
      1957), DLCO/(ThetaCO . Vc) was obtained by solving the relation DLCO/(ThetaCO .
      Vc) = 1 - 2/(DLNO/DLCO), where DLNO/DLCO represents the ratio between the
      respective single-breath diffusing capacities (DL) of nitric oxide (NO) and CO
      pulmonary capillary blood. The lungs of eight rabbits were inflated, starting
      from residual volume, by using 55 ml of indicator gas mixture (0.2% CO and 0.05%
      NO in nitrogen). DL values were calculated by taking the end-tidal partial
      pressures of CO and NO as analyzed by using a respiratory mass spectrometer. The
      overall value was DLCO/(ThetaCO . Vc) = 0.4 +/- 0.025 (mean +/- SD). Because of
      the use of O2-free indicator gas mixtures, the end-tidal O2 partial pressures
      were approximately 21 Torr. In one other rabbit, the application of 0.2% CO and
      0.001% NO yielded DLCO/(ThetaCO . Vc) = 0.39; in the tenth rabbit, however,
      inspiratory volume was varied, and an identical value was found at functional
      residual capacity. We conclude that the contribution of reaction resistance to
      overall resistance to pulmonary CO uptake is independent of the inspiratory NO
      concentration used, including, with respect to the pertinent literature, the
      conclusion that in rabbits, dogs, and humans this contribution amounts to 40%
      when determined at functional residual capacity.

PMID- 9609803
TI  - Modeling bronchial circulation with application to soluble gas exchange:
      description and sensitivity analysis.
AB  - The steady-state exchange of inert gases across an in situ canine trachea has
      recently been shown to be limited equally by diffusion and perfusion over a wide
      range (0.01-350) of blood solubilities (betablood; ml . ml-1 . atm-1). Hence, we
      hypothesize that the exchange of ethanol (betablood = 1,756 at 37 degrees C) in
      the airways depends on the blood flow rate from the bronchial circulation. To
      test this hypothesis, the dynamics of the bronchial circulation were incorporated
      into an existing model that describes the simultaneous exchange of heat, water,
      and a soluble gas in the airways. A detailed sensitivity analysis of key model
      parameters was performed by using the method of Latin hypercube sampling. The
      model accurately predicted a previously reported experimental exhalation profile
      of ethanol (R2 = 0.991) as well as the end-exhalation airstream temperature (34.6
      degrees C). The model predicts that 27, 29, and 44% of exhaled ethanol in a
      single exhalation are derived from the tissues of the mucosa and submucosa, the
      bronchial circulation, and the tissue exterior to the submucosa (which would
      include the pulmonary circulation), respectively. Although the concentration of
      ethanol in the bronchial capillary decreased during inspiration, the three key
      model outputs (end-exhaled ethanol concentration, the slope of phase III, and end
      exhaled temperature) were all statistically insensitive (P > 0.05) to the
      parameters describing the bronchial circulation. In contrast, the model outputs
      were all sensitive (P < 0.05) to the thickness of tissue separating the core body
      conditions from the bronchial smooth muscle. We conclude that both the bronchial
      circulation and the pulmonary circulation impact soluble gas exchange when the
      entire conducting airway tree is considered.

PMID- 9609804
TI  - Nicotine stimulates DNA synthesis and proliferation in vascular endothelial cells
      in vitro.
AB  - Nicotine is a major component of cigarette smoke and has been postulated to play
      an important role in atherogenesis and malignancy. Endothelial cell growth may be
      regulated by nicotine, yet operative mechanisms at the endothelial level are
      poorly understood. We studied the effects of nicotine (10(-14)-10(-4) M) on
      endothelial DNA synthesis, DNA repair, proliferation, and cytotoxicity by using
      cultures of bovine pulmonary artery endothelial cells. Assays were performed on
      cells incubated with nicotine in the presence and absence of hydroxyurea (an
      inhibitor of scheduled DNA synthesis), serum, human platelet-poor plasma, and
      platelet-derived growth factor and endothelial cell growth factor (PDGF and
      PDECGF, respectively). Nicotine significantly stimulated endothelial cell DNA
      synthesis and proliferation at concentrations lower than those obtained in blood
      after smoking (<10(-8) M). The stimulatory effects of nicotine were enhanced by
      serum (0.5%) and PDECGF and were blocked by the nicotinic-receptor antagonist
      hexamethonium. The response to nicotine was bimodal because cytotoxicity was
      observed at higher concentrations (>10(-6) M). This study has implications for
      understanding cellular mechanisms of nicotine action. The results may be
      important in tumor angiogenesis, atherogenesis, and vascular dysfunction in
      smokers.

PMID- 9609805
TI  - Hypercapnia-induced long-term depression of respiratory activity requires alpha2
      adrenergic receptors.
AB  - We investigated the effects of repeated hypercapnic episodes (inspired CO2
      fraction = 0.10) on posthypercapnic respiratory nerve discharge. Anesthetized
      (urethan), vagotomized, and artificially ventilated rats were presented with
      three consecutive 5-min episodes of hyperoxic hypercapnia, separated by 5 min of
      hyperoxic normocapnia (inspired O2 fraction = 0.5). Respiratory nerve discharge
      and blood gases were recorded before and 30 and 60 min after the final
      hypercapnic episode. Posthypercapnia, arterial PCO2 was maintained within 1 Torr
      of initial baseline values. Integrated phrenic and hypoglossal burst amplitudes
      decreased posthypercapnia by up to 46 +/- 17 and 55 +/- 13% of baseline values,
      respectively, and remained reduced for at least 1 h [long-term depression (LTD)].
      The protocol was repeated in rats pretreated with the alpha2-adrenergic
      antagonists yohimbine HCl (0.5 mg/kg; n = 7) or 2-[2-(2-methoxy-1,4
      benzodioanyl)]imidazoline (RX-821002) HCl (0.25 mg/kg; n = 3). Both drugs
      attenuated LTD in the phrenic and hypoglossal neurograms. Results indicate that
      episodic hypercapnia elicits a yohimbine- and RX-821002-sensitive LTD of
      respiratory nerve activity in rats, suggesting that LTD requires alpha2-receptor
      activation.

PMID- 9609806
TI  - Elicited pontogeniculooccipital waves and phasic suppression of diaphragm
      activity in sleep and wakefulness.
AB  - Fractionations are 20- to 100-ms pauses in diaphragm activity that occur
      spontaneously during rapid-eye-movement (REM) sleep, sometimes in association
      with pontogeniculooccipital (PGO) waves. Auditory stimuli can elicit
      fractionations or PGO waves during REM sleep, non-REM (NREM) sleep, and waking;
      however, their interrelationship has not been investigated. To determine whether
      the two phenomena are produced by a common phasic-event generator in REM sleep,
      we examined PGO waves and fractionations that were elicited by auditory stimuli
      (tones) presented to freely behaving cats across states. Tones elicited PGO waves
      and two types of fractionations: short-latency fractionation responses (SFRs; 10-
      to 60-ms latencies) and long-latency fractionation responses (LFRs; 60- to 120-ms
      latencies). Both a PGO wave and a SFR were elicited in 60-70% of trials across
      states, but each could be elicited alone. The latencies and durations of elicited
      SFRs were similar across states, but the latencies of elicited PGO waves in REM
      sleep (mean 62.5 ms) were significantly longer than in waking or NREM sleep.
      Elicited SFRs consistently occur with shorter latencies than do PGO waves, in
      contrast to spontaneous fractionations, which have a variable relationship to PGO
      waves and usually occur 10-40 ms after the onset of the PGO wave. The LFR then,
      elicited most frequently during REM sleep, resembles a spontaneous fractionation
      in its temporal relationship to the PGO wave and may reflect the bias toward
      motoneuronal inhibition characterizing REM sleep but not NREM sleep or waking. We
      conclude that, although PGO waves and SFRs share some features, like LFRs they
      probably are generated by different neuronal populations. In three cats there was
      no correlation between PGO waves and fractionations, whereas in one cat they were
      associated in REM sleep (LFRs and SFRs) and waking (SFRs only). Thus the majority
      of evidence argues against the existence of a common phasic-event generator in
      REM sleep.

PMID- 9609807
TI  - Effect of alae nasi activation on maximal nasal inspiratory airflow in humans.
AB  - The upper airway is a complicated structure that is usually widely patent during
      inspiration. However, on inspiration during certain physiological and
      pathophysiological states, the nares, pharynx, and larynx may collapse. Collapse
      at these locations occurs when the transmural pressure (Ptm) at a flow-limiting
      site (FLS) falls below a critical level (Ptm'). On airway collapse, inspiratory
      airflow is limited to a maximal level (VImax) determined by (-Ptm')/Rus, where
      Rus is the resistance upstream to the FLS. The airflow dynamics of the upper
      airway are affected by the activity of its associated muscles. In this study, we
      examine the modulation of VImax by muscle activity in the nasal airway under
      conditions of inspiratory airflow limitation. Each of six subjects performed
      sniffs through one patent nostril (pretreated with an alpha agonist) while
      flaring the nostril at varying levels of dilator muscle (alae nasi) EMG activity
      (EMGan). For each sniff, we located the nasal FLS with an airway catheter and
      determined VImax, Ptm', and Rus. Activation of the alae nasi from the lowest to
      the highest values of EMGan increased VImax from 422 +/- 156 to 753 +/- 291 ml/s
      (P < 0.01) and decreased Ptm' from -3.6 +/- 3.0 to -6.0 +/- 4.7 cmH2O (P < 0.05).
      Activation of the alae nasi had no consistent effect on Rus. VImax was positively
      correlated with EMGan, and Ptm' was negatively correlated with EMGan in all
      subjects. Our findings demonstrate that alae nasi activation increases VImax
      through the nasal airway by decreasing airway collapsibility.

PMID- 9609808
TI  - Load compensation as a function of state during sleep onset.
AB  - Ventilation decreases and airway resistance increases with the loss of
      electroencephalogram alpha activity at sleep onset. The aim of this study was to
      determine whether reflexive load compensation is lost immediately on the loss of
      alpha activity. Six healthy male subjects were studied under two conditions (load
      and control-no load), in three states (continuous alpha, continuous theta, and
      immediately after a transition from alpha to theta), and in two phases (early and
      late sleep onset). Ventilation and respiratory timing were measured. A comparison
      of loaded with control conditions indicated that loading had no effect on
      inspiratory minute ventilation during continuous alpha (differential effect of
      0.00 l/min) and only a small, nonsignificant effect in theta immediately after
      phase 2 transitions (0.31 l/min), indicating a preservation of load compensation
      at these times. However, there were significant decreases in inspiratory minute
      ventilation on loaded trials during continuous theta in phase 2 (0.77 l/min) and
      phase 3 (1.15 l/min) and during theta immediately after a transition in phase 3
      (0.87 l/min), indicating a lack of reflexive load compensation. The results
      indicate that, because reflex load compensation is state dependent, state-related
      changes in airway resistance contribute to state-related changes in ventilation
      during sleep onset. However, this effect was slightly delayed with transitions
      into theta early in sleep.

PMID- 9609809
TI  - Spaceflight has compartment- and gene-specific effects on mRNA levels for bone
      matrix proteins in rat femur.
AB  - In the present study, we evaluated the possibility that the abnormal bone matrix
      produced during spaceflight may be associated with reduced expression of bone
      matrix protein genes. To test this possibility, we investigated the effects of a
      14-day spaceflight (SLS-2 experiment) on steady-state mRNA levels for
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH), osteocalcin, osteonectin, and
      prepro-alpha(1) subunit of type I collagen in the major bone compartments of rat
      femur. There were pronounced site-specific differences in the steady-state levels
      of expression of the mRNAs for the three bone matrix proteins and GAPDH in normal
      weight-bearing rats, and these relationships were altered after spaceflight.
      Specifically, spaceflight resulted in decreases in mRNA levels for GAPDH
      (decreased in proximal metaphysis), osteocalcin (decreased in proximal
      metaphysis), osteonectin (decreased in proximal and distal metaphysis), and
      collagen (decreased in proximal and distal metaphysis) compared with ground
      controls. There were no changes in mRNA levels for matrix proteins or GAPDH in
      the shaft and distal epiphysis. These results demonstrate that spaceflight leads
      to site- and gene-specific decreases in mRNA levels for bone matrix proteins.
      These findings are consistent with the hypothesis that spaceflight-induced
      decreases in bone formation are caused by concomitant decreases in expression of
      genes for bone matrix proteins.

PMID- 9609810
TI  - Muscle performance and enzymatic adaptations to sprint interval training.
AB  - Our purpose was to examine the effects of sprint interval training on muscle
      glycolytic and oxidative enzyme activity and exercise performance. Twelve healthy
      men (22 +/- 2 yr of age) underwent intense interval training on a cycle ergometer
      for 7 wk. Training consisted of 30-s maximum sprint efforts (Wingate protocol)
      interspersed by 2-4 min of recovery, performed three times per week. The program
      began with four intervals with 4 min of recovery per session in week 1 and
      progressed to 10 intervals with 2.5 min of recovery per session by week 7. Peak
      power output and total work over repeated maximal 30-s efforts and maximal oxygen
      consumption (VO2 max) were measured before and after the training program. Needle
      biopsies were taken from vastus lateralis of nine subjects before and after the
      program and assayed for the maximal activity of hexokinase, total glycogen
      phosphorylase, phosphofructokinase, lactate dehydrogenase, citrate synthase,
      succinate dehydrogenase, malate dehydrogenase, and 3-hydroxyacyl-CoA
      dehydrogenase. The training program resulted in significant increases in peak
      power output, total work over 30 s, and VO2 max. Maximal enzyme activity of
      hexokinase, phosphofructokinase, citrate synthase, succinate dehydrogenase, and
      malate dehydrogenase was also significantly (P < 0.05) higher after training. It
      was concluded that relatively brief but intense sprint training can result in an
      increase in both glycolytic and oxidative enzyme activity, maximum short-term
      power output, and VO2 max.

PMID- 9609811
TI  - Regional measurements of pulmonary edema by using magnetic resonance imaging.
AB  - A three-dimensional magnetic resonance imaging (MRI) method to measure pulmonary
      edema and lung microvascular barrier permeability was developed and compared with
      conventional methods in nine mongrel dogs. MRIs were obtained covering the entire
      lungs. Injury was induced by injection of oleic acid (0.021-0.048 ml/kg) into a
      jugular catheter. Imaging followed for 0.75-2 h. Extravascular lung water and
      permeability-related parameters were measured from multiple-indicator dilution
      curves. Edema was measured as magnetic resonance signal-to-noise ratio (SNR).
      Postinjury wet-to-dry lung weight ratio was 5.30 +/- 0.38 (n = 9). Extravascular
      lung water increased from 2.03 +/- 1.11 to 3.00 +/- 1.45 ml/g (n = 9, P < 0.01).
      Indicator dilution studies yielded parameters characterizing capillary exchange
      of urea and butanediol: the product of the square root of equivalent diffusivity
      of escape from the capillary and capillary surface area (D1/2S) and the capillary
      permeability-surface area product (PS). The ratio of D1/2S for urea to D1/2S for
      butanediol increased from 0.583 +/- 0.027 to 0.852 +/- 0.154 (n = 9, P < 0.05).
      Whole lung SNR at baseline, before injury, correlated with D1/2S and PS ratios
      (both P < 0.02). By using rate of SNR change, the mismatch of transcapillary
      filtration flow and lymph clearance was estimated to be 0.2-1.8 ml/min. The
      filtration coefficient was estimated from these values. Results indicate that
      pulmonary edema formation during oleic acid injury can be imaged regionally and
      quantified globally, and the results suggest possible regional quantification by
      using three-dimensional MRI.

PMID- 9609812
TI  - Rapid determination of glomerular filtration rate by single-bolus inulin: a
      comparison of estimation analyses.
AB  - Rapid measurement of glomerular filtration rate (GFR) by an inulin single-bolus
      technique would be useful, but its accuracy has been questioned. We hypothesized
      that reported inaccuracies reflect the use of inappropriate mathematical models.
      GFR was measured in 14 intact and 5 unilaterally nephrectomized conscious male
      Sprague-Dawley rats (mean weight 368 +/- 12 g) by both single-bolus (25 mg/kg)
      and constant-infusion techniques (0.693 mg . kg-1 . min-1). The temporal decline
      in plasma inulin concentration was analyzed through biexponential curve fitting,
      which accounted for renal inulin loss before complete vascular and interstitial
      mixing. We compared our mathematical model based on empirical rationale with
      those of other investigators whose studies suggest inaccuracy of single-bolus
      methods. Our mathematical model yielded GFR values by single bolus that agreed
      with those obtained by constant infusion [slope = 0.94 +/- 0.16 (SE); y intercept
      = 0.23 +/- 0.64; r = 0.82]. In comparison to the data obtained by constant inulin
      infusion, this method yielded a very small bias of -0.0041 +/- 0.19 ml/min. Two
      previously reported models yielded unsatisfactory values (slope = 1. 46 +/- 0.34,
      y intercept = 0.47 +/- 1.5, r = 0.72; and slope = 0.17 +/- 1.26, y intercept =
      17.15 +/- 5.14, r = 0.03). The biases obtained by using these methods were -2.21
      +/- 0.42 and -13.90 +/- 1. 44 ml/min, respectively. The data indicate that when
      appropriate mathematical models are used, inulin clearance after single-bolus
      delivery can be used to measure GFR equivalent to that obtained by constant
      infusion of inulin. Attempts to use methods of analysis for simplicity or
      expediency can result in unacceptable measurements relative to the clinical range
      of values seen.

PMID- 9609813
TI  - Predictors of age-associated decline in maximal aerobic capacity: a comparison of
      four statistical models.
AB  - Studies assessing changes in maximal aerobic capacity (VO2 max) associated with
      aging have traditionally employed the ratio of VO2 max to body weight. Log
      linear, ordinary least-squares, and weighted least-squares models may avoid some
      of the inherent weaknesses associated with the use of ratios. In this study we
      used four different methods to examine the age-associated decline in VO2 max in a
      cross-sectional sample of 276 healthy men, aged 45-80 yr. Sixty-one of the men
      were aerobically trained athletes, and the remainder were sedentary. The model
      that accounted for the largest proportion of variance was a weighted least
      squares model that included age, fat-free mass, and an indicator variable
      denoting exercise training status. The model accounted for 66% of the variance in
      VO2 max and satisfied all the important general linear model assumptions. The
      other approaches failed to satisfy one or more of these assumptions. The results
      indicated that VO2 max declines at the same rate in athletic and sedentary men
      (0.24 l/min or 9%/decade) and that 35% of this decline (0.08 l . min-1 . decade
      1) is due to the age-associated loss of fat-free mass.

PMID- 9609814
TI  - A stimulating nerve cuff for chronic in vivo measurements of torque produced
      about the ankle in the mouse.
AB  - Specific muscle training and chronic contractile measurements are difficult in
      rodents, especially in the mouse. The primary reason for this is the lack of a
      means for stimulating the motor nerve that does not damage the nerve and that
      permits reproducible measurements of contractility. In this paper, we describe
      procedures for the construction and implantation of a stimulating nerve cuff for
      use on the mouse common peroneal nerve. We demonstrate that nerve cuff
      implantation success rates can be high (i.e., 75-93%), as determined from
      measurements of maximal isometric torque produced by the anterior crural muscles.
      Isometric torque production is not adversely affected by the nerve cuff because
      the torque produced matches that observed in our established percutaneous
      stimulation model. We also demonstrate that use of the nerve cuff for stimulation
      is compatible with electromyographic measurements made on the tibialis anterior
      muscle, with no sign of stimulation artifact in the electromyographic signal.

PMID- 9609815
TI  - Quantitative methanol-burning lung model for validating gas-exchange measurements
      over wide ranges of FIO2.
AB  - The methanol-burning lung model has been used as a technique for generating a
      predictable ratio of carbon dioxide production (VCO2) to oxygen consumption (VO2)
      or respiratory quotient (RQ). Although an accurate RQ can be generated,
      quantitatively predictable and adjustable VO2 and VCO2 cannot be generated. We
      describe a new burner device in which the combustion rate of methanol is always
      equal to the infusion rate of fuel over an extended range of O2 concentrations.
      This permits the assembly of a methanol-burning lung model that is usable with O2
      concentrations up to 100% and provides continuously adjustable and quantitative
      VO2 (69-1,525 ml/min) and VCO2 (46-1,016 ml/min) at a RQ of 0.667.

PMID- 9609816
TI  - Hypertrophy of rat plantaris muscle fibers after voluntary running with
      increasing loads.
AB  - There have been no systematic comparisons of skeletal muscle adaptations in
      response to voluntary wheel running under controlled loading conditions. To
      accomplish this, a voluntary running wheel for rats and mice was developed in
      which a known load can be controlled and monitored electronically. Five-week-old
      male Sprague-Dawley rats (10 rats/group) were assigned randomly to either a 1)
      sedentary control group (Control); 2) voluntary exercised with no load (Run-No
      Load) group; or 3) voluntary exercised with additional load (Run-Load) group for
      8 wk. The load for the Run-Load group was progressively increased to reach
      approximately 60% of body weight during the last week of training. The
      proportions of fast glycolytic (FG), fast oxidative glycolytic (FOG), or slow
      oxidative (SO) fibers in the plantaris were similar in all groups. The absolute
      and relative plantaris weights were greater in the Run-Load group compared with
      the Control and Run-No-Load groups. The mean fiber cross-sectional areas of FG,
      FOG, and SO fibers were 20, 25, and 15% greater in the Run-Load than in Control
      rats. In addition, these fiber types were 16, 21, and 12% larger in Run-Load than
      in Run-No-Load rats. The muscle weights and mean cross-sectional areas of each
      fiber type were highly correlated with the average running distances and total
      work performed in the Run-Load, but not the Run-No-Load, group. The slope of the
      relationship between fiber size and running distance and total work performed was
      significant for each fiber type but was higher for FG and FOG fibers compared
      with SO fibers. These data show that the load on a rat running voluntarily can
      determine the magnitude of a hypertrophic response and the population of motor
      units that are recruited to perform at a given loading condition.

PMID- 9609817
TI  - A new approach to normalize myocardial temperature in the open-chest pig model.
AB  - To prevent unphysiological temperature fluctuations in the myocardium in the open
      chest model, we constructed a thermocage. Five pigs under pentobarbital sodium
      anesthesia underwent repetitive left anterior descending (LAD) coronary artery
      occlusions. Myocardial temperature was measured without any thoracic temperature
      controlling device and in the presence of either a heating lamp or the
      thermocage. Without any thoracic temperature-controlling device, the temperature
      at 5-mm myocardial depth was 1.28 +/- 0.33 degrees C below the intra-abdominal
      temperature (P < 0.05). During a proximal 5-min LAD occlusion, myocardial
      temperature decreased by 1.86 +/- 1.02 degrees C in the ischemic area (P < 0.05).
      Both the heating lamp and the thermocage abolished the difference between intra
      abdominal and myocardial temperatures and prevented the decrease in myocardial
      temperature during ischemia. Only the thermocage minimized myocardial temperature
      fluctuations due to air currents and prevented epicardial exsiccation. We
      conclude that either a thermocage or a heating lamp may be used to normalize
      myocardial temperature in the open-chest pig model. However, the thermocage is
      superior to the lamp in minimizing temperature fluctuations and preventing
      epicardial exsiccation.

PMID- 9609818
TI  - Overlapping functions of the myogenic bHLH genes MRF4 and MyoD revealed in double
      mutant mice.
AB  - The myogenic basic helix-loop-helix (bHLH) genes - MyoD, Myf5, myogenin and MRF4 
      exhibit distinct, but overlapping expression patterns during development of the
      skeletal muscle lineage and loss-of-function mutations in these genes result in
      different effects on muscle development. MyoD and Myf5 have been shown to act
      early in the myogenic lineage to establish myoblast identity, whereas myogenin
      acts later to control myoblast differentiation. In mice lacking myogenin, there
      is a severe deficiency of skeletal muscle, but some residual muscle fibers are
      present in mutant mice at birth. Mice lacking MRF4 are viable and have skeletal
      muscle, but they upregulate myogenin expression, which could potentially
      compensate for the absence of MRF4. Previous studies in which Myf5 and MRF4 null
      mutations were combined suggested that these genes do not share overlapping
      myogenic functions in vivo. To determine whether the functions of MRF4 might
      overlap with those of myogenin or MyoD, we generated double mutant mice lacking
      MRF4 and either myogenin or MyoD. MRF4/myogenin double mutant mice contained a
      comparable number of residual muscle fibers to mice lacking myogenin alone and
      myoblasts from those double mutant mice formed differentiated multinucleated
      myotubes in vitro as efficiently as wild-type myoblasts, indicating that neither
      myogenin nor MRF4 is absolutely essential for myoblast differentiation. Whereas
      mice lacking either MRF4 or MyoD were viable and did not show defects in muscle
      development, MRF4/MyoD double mutants displayed a severe muscle deficiency
      similar to that in myogenin mutants. Myogenin was expressed in MRF4/MyoD double
      mutants, indicating that myogenin is insufficient to support normal myogenesis in
      vivo. These results reveal unanticipated compensatory roles for MRF4 and MyoD in
      the muscle differentiation pathway and suggest that a threshold level of myogenic
      bHLH factors is required to activate muscle structural genes, with this level
      normally being achieved by combinations of multiple myogenic bHLH factors.

PMID- 9609819
TI  - Control of floral homeotic gene expression and organ morphogenesis in
      Antirrhinum.
AB  - The development of reproductive organs in Antirrhinum depends on the expression
      of an organ identity gene, plena, in the central domain of the floral meristem.
      To investigate the mechanism by which plena is regulated, we have characterised
      three mutants in which the pattern of plena expression is altered. In polypetala
      mutants, expression of plena is greatly reduced, resulting in a proliferation of
      petals in place of reproductive organs. In addition, polypetala mutants exhibit
      an altered pattern of floral organ initiation, quite unlike that seen in loss-of
      function plena mutants. This suggests that polypetala normally has two roles in
      flower development: regulation of plena and control of organ primordia formation.
      In fistulata mutants, plena is ectopically expressed in the distal domain of
      petal primordia, resulting in the production of anther-like tissue in place of
      petal lobes. Flowers of fistulata mutants also show a reduced rate of petal lobe
      growth, even in a plena mutant background. This implies that fistulata normally
      has two roles in the distal domain of petal primordia: inhibition of plena
      expression and promotion of lobe growth. A weak allele of the floral meristem
      identity gene, floricaula, greatly enhances the effect of fistulata on plena
      expression, showing that floricaula also plays a role in repression of plena in
      outer whorls. Taken together, these results show that genes involved in plena
      regulation have additional roles in the formation of organs, perhaps reflecting
      underlying mechanisms for coupling homeotic gene expression to morphogenesis.

PMID- 9609820
TI  - A role for the vegetally expressed Xenopus gene Mix.1 in endoderm formation and
      in the restriction of mesoderm to the marginal zone.
AB  - We have studied the role of the activin immediate-early response gene Mix.1 in
      mesoderm and endoderm formation. In early gastrulae, Mix.1 is expressed
      throughout the vegetal hemisphere, including marginal-zone cells expressing the
      trunk mesodermal marker Xbra. During gastrulation, the expression domains of Xbra
      and Mix.1 become progressively exclusive as a result of the establishment of a
      negative regulatory loop between these two genes. This mutual repression is
      important for the specification of the embryonic body plan as ectopic expression
      of Mix.1 in the Xbra domain suppresses mesoderm differentiation. The same effect
      was obtained by overexpressing VP16Mix.1, a fusion protein comprising the strong
      activator domain of viral VP16 and the homeodomain of Mix.1, suggesting that
      Mix.1 acts as a transcriptional activator. Mix.1 also has a role in endoderm
      formation. It cooperates with the dorsal vegetal homeobox gene Siamois to
      activate the endodermal markers edd, Xlhbox8 and cerberus in animal caps.
      Conversely, vegetal overexpression of enRMix.1, an antimorphic Mix.1 mutant,
      leads to a loss of endoderm differentiation. Finally, by targeting enRMix.1
      expression to the anterior endoderm, we could test the role of this tissue during
      embryogenesis and show that it is required for head formation.

PMID- 9609821
TI  - Fgf8 is mutated in zebrafish acerebellar (ace) mutants and is required for
      maintenance of midbrain-hindbrain boundary development and somitogenesis.
AB  - We describe the isolation of zebrafish Fgf8 and its expression during
      gastrulation, somitogenesis, fin bud and early brain development. By
      demonstrating genetic linkage and by analysing the structure of the Fgf8 gene, we
      show that acerebellar is a zebrafish Fgf8 mutation that may inactivate Fgf8
      function. Homozygous acerebellar embryos lack a cerebellum and the midbrain
      hindbrain boundary organizer. Fgf8 function is required to maintain, but not
      initiate, expression of Pax2.1 and other marker genes in this area. We show that
      Fgf8 and Pax2.1 are activated in adjacent domains that only later become
      overlapping, and activation of Fgf8 occurs normally in no isthmus embryos that
      are mutant for Pax2.1. These findings suggest that multiple signaling pathways
      are independently activated in the midbrain-hindbrain boundary primordium during
      gastrulation, and that Fgf8 functions later during somitogenesis to polarize the
      midbrain. Fgf8 is also expressed in a dorsoventral gradient during gastrulation
      and ectopically expressed Fgf8 can dorsalize embryos. Nevertheless, acerebellar
      mutants show only mild dorsoventral patterning defects. Also, in spite of the
      prominent role suggested for Fgf8 in limb development, the pectoral fins are
      largely unaffected in the mutants. Fgf8 is therefore required in development of
      several important signaling centers in the zebrafish embryo, but may be redundant
      or dispensable for others.

PMID- 9609822
TI  - Complete dissipation of coherent clonal growth occurs before gastrulation in
      mouse epiblast.
AB  - Observations on chimaeric mice argue that there must be considerable dispersal
      and intermingling of the clonal descendants of epiblast founder cells at an early
      stage in the development of the tissue. However, it has not been established when
      or how this occurs. Here we have used a genetic marker that enables donor cells
      to be visualized in situ to examine the early postimplantation distribution of
      clones obtained by transplanting epiblast founder cells into host blastocysts. We
      have also determined the spatial relationship between sister cells in non
      chimaeric postimplantation epiblast by ionophoretic injection of a fluorescent
      macromolecule. Both experimental approaches support the conclusion that breakdown
      of coherent clonal growth accompanies epithelialization of the epiblast and is
      essentially complete by the onset of gastrulation. Furthermore, the clonal
      analysis shows that descendants of different epiblast founder cells continue to
      intermingle extensively well into organogenesis. We suggest that this sustained
      intermingling of cells in the epithelial epiblast, which does not occur in the
      adjacent visceral endoderm, depends on cells losing contact with the basal lamina
      when they divide. These findings have implications both for patterning of the
      early amniote embryo and for the growth of tall columnar epithelia in general.

PMID- 9609823
TI  - Neural crest induction in Xenopus: evidence for a two-signal model.
AB  - We have investigated the molecular interactions underlying neural crest formation
      in Xenopus. Using chordin overexpression to antagonize endogenous BMP signaling
      in whole embryos and explants, we demonstrate that such inhibition alone is
      insufficient to account for neural crest induction in vivo. We find, however,
      that chordin-induced neural plate tissue can be induced to adopt neural crest
      fates by members of the FGF and Wnt families, growth factors that have previously
      been shown to posteriorize induced neural tissue. Overexpression of a dominant
      negative XWnt-8 inhibits the expression of neural crest markers, demonstrating
      the necessity for a Wnt signal during neural crest induction in vivo. The
      requirement for Wnt signaling during neural crest induction is shown to be
      direct, whereas FGF-mediated neural crest induction may be mediated by Wnt
      signals. Overexpression of the zinc finger transcription factor Slug, one of the
      earliest markers of neural crest formation, is insufficient for neural crest
      induction. Slug-expressing ectoderm will generate neural crest in the presence of
      Wnt or FGF-like signals, however, bypassing the need for BMP inhibition in this
      process. A two-step model for neural crest induction is proposed.

PMID- 9609824
TI  - Human ZP3 restores fertility in Zp3 null mice without affecting order-specific
      sperm binding.
AB  - The mammalian zona pellucida surrounding ovulated eggs mediates sperm binding at
      fertilization, provides a postfertilization block to polyspermy, and facilitates
      passage of pre-implantation embryos down the oviduct. Although the three zona
      proteins (ZP1, ZP2, ZP3) are well conserved, mammalian fertilization is
      relatively specific and human sperm do not bind to the mouse zona pellucida.
      There are considerable in vitro data that ZP3 acts as a primary sperm adhesion
      molecule in mice and, by analogy, a similar role has been postulated for human
      ZP3. Genetically altered mice lacking ZP3 (Zp3(tm/tm)) do not form a zona
      pellucida and are infertile. To rescue this phenotype, transgenic mice expressing
      human ZP3 (67% identical to mouse ZP3) were produced and bred with Zp3(tm/tm)
      null mice. The resultant human ZP3 rescue females had chimeric zonae pellucidae
      composed of mouse ZP1, mouse ZP2 and human ZP3. Human ZP3 expressed in mouse
      oocytes had an apparent mass (64 kDa) indistinguishable from native human ZP3 and
      distinct from mouse ZP3 (83 kDa). Despite the presence of human ZP3, human sperm
      did not bind to the chimeric zona pellucida, and notwithstanding the absence of
      mouse ZP3, mouse sperm bound to ovulated eggs in vitro and fertility was restored
      in vivo. These data have implications regarding the molecular basis of mouse and
      human sperm binding to their respective zonae pellucidae.

PMID- 9609825
TI  - The Xenopus homologue of the Drosophila gene tailless has a function in early eye
      development.
AB  - Genetic circuits responsible for the development of photoreceptive organs appear
      to be evolutionarily conserved. Here, the Xenopus homologue Xtll of the
      Drosophila gene tailless (tll), which we find to be expressed during early eye
      development, is characterized with respect to its relationship to vertebrate
      regulators of eye morphogenesis, such as Pax6 and Rx. Expression of all three
      genes is first detected in the area corresponding to the eye anlagen within the
      open neural plate in partially overlapping, but not identical, patterns. During
      the evagination of the optic vesicle, Xtll expression is most prominent in the
      optic stalk, as well as in the distal tip of the forming vesicle. In tadpole
      stage embryos, Xtll gene transcription is most prominent in the ciliary margin of
      the optic cup. Inhibition of Xtll function in Xenopus embryos interferes
      specifically with the evagination of the eye vesicle and, in consequence, Xpax6
      gene expression is severely reduced in such manipulated embryos. These findings
      suggest that Xtll serves an important regulatory function in the earliest phases
      of vertebrate eye development.

PMID- 9609826
TI  - Role of caudal in hindgut specification and gastrulation suggests homology
      between Drosophila amnioproctodeal invagination and vertebrate blastopore.
AB  - During early embryogenesis in Drosophila, caudal mRNA is distributed as a
      gradient with its highest level at the posterior of the embryo. This suggests
      that the Caudal homeodomain transcription factor might play a role in
      establishing the posterior domains of the embryo that undergo gastrulation and
      give rise to the posterior gut. By generating embryos lacking both the maternal
      and zygotic mRNA contribution, we show that caudal is essential for invagination
      of the hindgut primordium and for further specification and development of the
      hindgut. These effects are achieved by the function of caudal in activating
      different target genes, namely folded gastrulation, which is required for
      invagination of the posterior gut primordium, and fork head and wingless, which
      are required to promote development of the internalized hindgut primordium.
      caudal is not sufficient for hindgut gastrulation and development, however, as it
      does not play a significant role in activating expression of the genes tailless,
      huckebein, brachyenteron and bowel. We argue that caudal and other genes
      expressed at the posterior of the Drosophila embryo (fork head, brachyenteron and
      wingless) constitute a conserved constellation of genes that plays a required
      role in gastrulation and gut development.

PMID- 9609827
TI  - Recruitment of Tube and Pelle to signaling sites at the surface of the Drosophila
      embryo.
AB  - A signaling pathway initiated by activation of the transmembrane receptor Toll
      defines dorsoventral polarity in the Drosophila embryo. Toll, which is present
      over the entire surface of the embryo, is activated ventrally by interaction with
      a spatially restricted, extracellular ligand. Tube and Pelle then transduce the
      signal from activated Toll to a complex of Dorsal and Cactus. Here we demonstrate
      by an mRNA microinjection assay that targeting of either Tube or Pelle to the
      plasma membrane by myristylation is sufficient to activate the signal
      transduction pathway that leads to Dorsal nuclear translocation. Using confocal
      immunofluorescence microscopy we also show that activated Toll induces a
      localized recruitment of Tube and Pelle to the plasma membrane. Together, these
      results strongly support the hypothesis that intracellular signaling requires the
      Toll-mediated formation of a membrane-associated complex containing both Tube and
      Pelle.

PMID- 9609828
TI  - Chromatin silencing and the maintenance of a functional germline in
      Caenorhabditis elegans.
AB  - The germline of the nematode Caenorhabditis elegans exhibits a remarkable ability
      to specifically silence transgenic DNA. We have shown that this silencing
      mechanism is disrupted in animals mutant for the maternal effect sterile genes
      mes-2, mes-3, mes-4 and mes-6. The proteins encoded by mes-2 and mes-6 have been
      shown to be related to the Polycomb Group of transcriptional repressors
      (Holdeman, R., Nehrt, S. and Strome, S. (1998). Development 125, 2457-2467; Korf,
      I., Fan, F. and Strome, S. (1998). Development 125, 2469-2478). These results
      suggest that a genetic silencing process is essential for sustained germline
      function, and that this silencing is mediated, at least in part, by Polycomb
      Group proteins.

PMID- 9609829
TI  - MES-2, a maternal protein essential for viability of the germline in
      Caenorhabditis elegans, is homologous to a Drosophila Polycomb group protein.
AB  - A unique and essential feature of germ cells is their immortality. In
      Caenorhabditis elegans, germline immortality requires the maternal contribution
      from four genes, mes-2, mes-3, mes-4 and mes-6. We report here that mes-2 encodes
      a protein similar to the Drosophila Polycomb group protein, Enhancer of zeste,
      and in the accompanying paper that mes-6 encodes another Polycomb group protein.
      The Polycomb group is responsible for maintaining proper patterns of expression
      of the homeotic and other genes in Drosophila. It is thought that Polycomb group
      proteins form heteromeric complexes and control gene expression by altering
      chromatin conformation of target genes. As predicted from its similarity to a
      Polycomb group protein, MES-2 localizes to nuclei. MES-2 is found in germline
      nuclei in larval and adult worms and in all nuclei in early embryos. By the end
      of embryogenesis, MES-2 is detected primarily in the two primordial germ cells.
      The correct distribution of MES-2 requires the wild-type functions of mes-3 and
      mes-6. We hypothesize that mes-2 encodes a maternal regulator of gene expression
      in the early germline; its function is essential for normal early development and
      viability of germ cells.

PMID- 9609830
TI  - The Polycomb group in Caenorhabditis elegans and maternal control of germline
      development.
AB  - Four Caenorhabditis elegans genes, mes-2, mes-3, mes-4 and mes-6, are essential
      for normal proliferation and viability of the germline. Mutations in these genes
      cause a maternal-effect sterile (i.e. mes) or grandchildless phenotype. We report
      that the mes-6 gene is in an unusual operon, the second example of this type of
      operon in C. elegans, and encodes the nematode homolog of Extra sex combs, a WD
      40 protein in the Polycomb group in Drosophila. mes-2 encodes another Polycomb
      group protein (see paper by Holdeman, R., Nehrt, S. and Strome, S. (1998).
      Development 125, 2457-2467). Consistent with the known role of Polycomb group
      proteins in regulating gene expression, MES-6 is a nuclear protein. It is
      enriched in the germline of larvae and adults and is present in all nuclei of
      early embryos. Molecular epistasis results predict that the MES proteins, like
      Polycomb group proteins in Drosophila, function as a complex to regulate gene
      expression. Database searches reveal that there are considerably fewer Polycomb
      group genes in C. elegans than in Drosophila or vertebrates, and our studies
      suggest that their primary function is in controlling gene expression in the
      germline and ensuring the survival and proliferation of that tissue.

PMID- 9609831
TI  - MyoD and the specification of muscle and non-muscle fates during postembryonic
      development of the C. elegans mesoderm.
AB  - Basic-helix-loop helix factors of the myoD/myf5/ myogenin/MRF4 family have been
      implicated in acquisition and elaboration of muscle cell fates. Here we describe
      both myogenic and non-myogenic roles for the Caenorhabditis elegans member of
      this family (CeMyoD) in postembryonic mesodermal patterning. The postembryonic
      mesodermal lineage in C. elegans provides a paradigm for many of the issues in
      mesodermal fate specification: a single mesoblast ('M') divides to generate 14
      striated muscles, 16 non-striated muscles, and two non-muscle cells. To study
      CeMyoD function in the M lineage, we needed to circumvent an embryonic
      requirement for the protein. Two approaches were used: (1) isolation of mutants
      that decrease CeMyoD levels while retaining viability, and (2) analysis of
      genetic mosaics that had lost CeMyoD in the M lineage. With either manipulation,
      we observed a series of cell-fate transformations affecting a subset of both
      striated muscles and non-muscle cells. In place of these normal fates, the
      affected lineages produced a number of myoblast-like cells that initially failed
      to differentiate, instead swelling to acquire a resemblance to sex myoblasts (M
      lineage-derived precursors to non-striated uterine and vulval muscles). Like
      normal sex myoblasts, the ectopic myoblast-like cells were capable of migration
      and proliferation followed by differentiation of progeny cells into vulval and
      uterine muscle. Our results demonstrate a cell-intrinsic contribution of CeMyoD
      to specification of both non-muscle and muscle fates.

PMID- 9609832
TI  - GSK3beta/shaggy mediates patterning along the animal-vegetal axis of the sea
      urchin embryo.
AB  - In the sea urchin embryo, the animal-vegetal axis is defined before fertilization
      and different embryonic territories are established along this axis by mechanisms
      which are largely unknown. Significantly, the boundaries of these territories can
      be shifted by treatment with various reagents including zinc and lithium. We have
      isolated and characterized a sea urchin homolog of GSK3beta/shaggy, a lithium
      sensitive kinase which is a component of the Wnt pathway and known to be involved
      in axial patterning in other embryos including Xenopus. The effects of
      overexpressing the normal and mutant forms of GSK3beta derived either from sea
      urchin or Xenopus were analyzed by observation of the morphology of 48 hour
      embryos (pluteus stage) and by monitoring spatial expression of the hatching
      enzyme (HE) gene, a very early gene whose expression is restricted to an animal
      domain with a sharp border roughly coinciding with the future ectoderm / endoderm
      boundary. Inactive forms of GSK3beta predicted to have a dominant-negative
      activity, vegetalized the embryo and decreased the size of the HE expression
      domain, apparently by shifting the boundary towards the animal pole. These
      effects are similar to, but even stronger than, those of lithium. Conversely,
      overexpression of wild-type GSK3beta animalized the embryo and caused the HE
      domain to enlarge towards the vegetal pole. Unlike zinc treatment, GSK3beta
      overexpression thus appeared to provoke a true animalization, through extension
      of the presumptive ectoderm territory. These results indicate that in sea urchin
      embryos the level of GSKbeta activity controls the position of the boundary
      between the presumptive ectoderm and endoderm territories and thus, the relative
      extent of these tissue layers in late embryos. GSK3beta and probably other
      downstream components of the Wnt pathway thus mediate patterning both along the
      primary AV axis of the sea urchin embryo and along the dorsal-ventral axis in
      Xenopus, suggesting a conserved basis for axial patterning between invertebrate
      and vertebrate in deuterostomes.

PMID- 9609833
TI  - Involvement of T-box genes Tbx2-Tbx5 in vertebrate limb specification and
      development.
AB  - We have recently shown in mice that four members of the T-box family of
      transcription factors (Tbx2-Tbx5) are expressed in developing limb buds, and that
      expression of two of these genes, Tbx4 and Tbx5, is primarily restricted to the
      developing hindlimbs and forelimbs, respectively. In this report, we investigate
      the role of these genes in limb specification and development, using the chick as
      a model system. We induced the formation of ectopic limbs in the flank of chick
      embryos to examine the relationship between the identity of the limb-specific T
      box genes being expressed and the identity of limb structures that subsequently
      develop. We found that, whereas bud regions expressing Tbx4 developed
      characteristic leg structures, regions expressing Tbx5 developed characteristic
      wing features. In addition, heterotopic grafts of limb mesenchyme (wing bud into
      leg bud, and vice versa), which are known to retain the identity of the donor
      tissue after transplantation, retained autonomous expression of the appropriate,
      limb-specific T-box gene, with no evidence of regulation by the host bud. Thus
      there is a direct relationship between the identity of the structures that
      develop in normal, ectopic and recombinant limbs, and the identity of the T-box
      gene(s) being expressed. To investigate the regulation of T-box gene expression
      during limb development, we employed several other embryological manipulations.
      By surgically removing the apical ectodermal ridge (AER) from either wing or leg
      buds, we found that, in contrast to all other genes implicated in the patterning
      of developing appendages, maintenance of T-box gene expression is not dependent
      on the continued provision of signals from the AER or the zone of polarizing
      activity (ZPA). By generating an ectopic ZPA, by grafting a sonic hedgehog (SHH)
      expressing cell pellet under the anterior AER, we found that Tbx2 expression can
      lie downstream of SHH. Finally, by grafting a SHH-expressing cell pellet to the
      anterior margin of a bud from which the AER had been removed, we found that Tbx2
      may be a direct, short-range target of SHH. Our findings suggest that these genes
      are intimately involved in limb development and the specification of limb
      identity, and a new model for the evolution of vertebrate appendages is proposed.

PMID- 9609834
TI  - The snail repressor establishes a muscle/notochord boundary in the Ciona embryo.
AB  - Previous studies have identified a minimal 434 bp enhancer from the promoter
      region of the Ciona Brachyury gene (Ci-Bra), which is sufficient to direct a
      notochord-specific pattern of gene expression. Here we present evidence that a
      Ciona homolog of snail (Ci-sna) encodes a repressor of the Ci-Bra enhancer in the
      tail muscles. DNA-binding assays identified four Ci-Sna-binding sites in the Ci
      Bra enhancer, and mutations in these sites cause otherwise normal Ci-Bra/lacZ
      transgenes to be misexpressed in ectopic tissues, particularly the tail muscles.
      Selective misexpression of Ci-sna using a heterologous promoter results in the
      repression of Ci-Bra/lacZ transgenes in the notochord. Moreover, the conversion
      of the Ci-Sna repressor into an activator results in the ectopic induction of Ci
      Bra/lacZ transgenes in the muscles, and also causes an intermixing of notochord
      and muscle cells during tail morphogenesis. These results suggest that Ci-Sna
      functions as a boundary repressor, which subdivides the mesoderm into separate
      notochord and tail muscle lineages.

PMID- 9609835
TI  - Involvement of Sox1, 2 and 3 in the early and subsequent molecular events of lens
      induction.
AB  - Activation of the first lens-specific gene of the chicken, delta 1-crystallin, is
      dependent on a group of lens nuclear factors, deltaEF2, interacting with the
      delta1-crystallin minimal enhancer, DC5. One of the deltaEF2 factors was
      previously identified as SOX2. We show that two related SOX proteins, SOX1 and
      SOX3, account for the remaining members of deltaEF2. Activation of the DC5
      enhancer is dependent on their C-terminal domains. Expression of Sox1-3 in the
      eye region during lens induction was studied in comparison with Pax6 and delta1
      crystallin. Pax6, known to be required for the inductive response of the
      ectoderm, is broadly expressed in the lateral head ectoderm from before lens
      induction. After tight association of the optic vesicle (around stage 10-11, 40
      hours after egg incubation), expression of Sox2 and Sox3 is activated in the
      vesicle-facing ectoderm at stage 12 (44 hours). These cells, expressing together
      Pax6 and Sox2/3, subsequently give rise to the lens, beginning with formation of
      the lens placode and expression of delta-crystallin at stage 13 (48 hours). Sox1
      then starts to be expessed in the lens-forming cells at stage 14. When the
      prospective retina area of the neural plate was unilaterally ablated at stage 7,
      expression of Sox2/3 was lost in the side of lateral head ectoderm lacking the
      optic cup, implying that an inductive signal from the optic cup activates Sox2/3
      expression. In the mouse embryonic lens, this subfamily of Sox genes is expressed
      in an analogous fashion, although Sox3 transcripts have not been detected and
      Sox2 expression is down-regulated when Sox1 is activated. In ectodermal tissues
      of the chicken embryo, delta -crystallin expression occurs in a few ectopic
      sites. These are always characterized by overlapping expression of Sox2/3 and
      Pax6. Thus, an essential molecular event in lens induction is the 'turning on' of
      the transcriptional regulators SOX2/3 in the Pax6-expressing ectoderm and these
      SOX proteins activate crystallin gene expression. Continued activity, especially
      of SOX1, is then essential for further development of the lens.

PMID- 9609836
TI  - Human mutations affecting branched chain alpha-ketoacid dehydrogenase.
AB  - Maple syrup urine disease results from defective function of the branched chain
      alpha-ketoacid dehydrogenase complex [BCKD] within the matrix of the
      mitochondria. This disorder in humans is inherited as an autosomal recessive
      trait with an incidence of 1 in 150,000 live-births in the general population and
      1/176 for the Mennonite population. Over 50 different causal mutations are known
      to exist scattered among the three genes unique to the catalytic function of the
      enzyme complex. The defect was first described in 1954 and much has been learned
      about the genes and proteins involved in this rare human disorder. The enzyme is
      present in all mammalian cells that contain mitochondria, and the activity of
      BCKD is regulated by phosphorylation through a complex-specific kinase.
      Expression of the kinase is regulated by metabolic and hormonal components.
      Naturally occurring mutations are used to define the molecular mechanisms of
      transcription, translation, protein import into mitochondria and the assembly of
      the component proteins into a functional complex. The long-term pathophysiology
      of BCKD dysfunction remains to be explained. What began as a focused interest in
      BCKD due to the associated disease, has broadened into a quest to understand the
      role of BCKD in regulation of leucine levels and in turn controlling protein
      metabolism and hormone release.

PMID- 9609837
TI  - [Validation of the imagamma interface for connecting gamma cameras to personal
      computers].
AB  - An electronic interface, imagamma, has been designed in order to link analog
      gamma cameras to IBM personal computers (PCs). The performance of the interface
      was assessed for a camera-computer system composed by a GE Maxicamera II-400T
      gamma camera and an IBM PC, which has a DX 80486 processor, 8 Mb RAM and a
      suitable acquisition and processing software. Quality control tests for gamma
      camera-computer systems, established by the International Atomic Energy Agency in
      the IAEA-TECDOC-602 for <<Quality Control of Nuclear Medicine Instruments 1991>>,
      were performed. The main performance characteristics of the gamma camera:
      intrinsic flood field uniformity, intrinsic spatial resolution and spatial
      linearity were tested as well as the system time performance for dynamic and
      gated studies. The results obtained for the camera-computer system performance
      parameters show a good stability. Those results concerning the dynamic
      characteristics of the interface are between the limits of acceptability,
      established for each test by the IAEA standards. We conclude that the imagamma
      interface has suitable performance characteristics to link analog gamma cameras
      to PC based computer systems in order to be used with clinical application
      purposes.

PMID- 9609838
TI  - [Study of primary hyperparathyroidism by double-phase gammagraphy using Tc99m
      MIBI: preoperative detection of pathological glands].
AB  - The preoperative use of imaging techniques to localize the diseased glands in
      primary hyperparathyroidism is still the subject of controversy. This paper
      assess the use of double-phase 99mTc-MIBI scintigraphy with that purpose. We
      examined 37 patients with primary hyperparathyroidism before surgical
      intervention. Two planar images 10 minutes and 3 hours after injection of 99mTc
      MIBI were acquired. Final diagnosis was adenoma in 32 patients, 30 of whom had a
      positive scintigraphy (sensitivity 94%), with only two false negative results. In
      the other five patients, four with hyperplasia and one carcinoma, scintigraphy
      was also positive. Radioisotopic study was of particular interest in 5 patients
      who had undergone previous surgery; in one case, other diseased gland was located
      in the neck, and an ectopic adenoma was found in the remaining four cases. Two
      other ectopic lesions were also MIBI positive and, in these cases, scintigraphy
      was a direct indication for mediastinal surgery. There was no false positive
      results. We conclude that the high sensitivity and easy performance make double
      phase 99mTc-MIBI scintigraphy the technique of choice for the preoperative
      localization of diseased glands in primary hyperparathyroidism, especially in
      cases of adenoma. Its use is of particular interest in adenomas with aberrant
      location and in patients who have undergone previous surgery.

PMID- 9609839
TI  - [Detection of sentinel lymph nodes by lymphatic gammagraphy and intraoperative
      gamma-ray probe in patients with malignant melanoma. Initial results].
AB  - In the last years there has been an arising concern in the sentinel lymph node
      identification, the first lymph node to receive direct draining from the primary
      tumour, specially in malignant melanoma (MM). We studied 20 patients with MM: 10
      with palpable regional lymph nodes and 10 without palpable LN by performing a
      lymphoscintigraphy using 99mTc-nanocolloid and a gamma-ray detecting probe during
      the surgery to locate the sentinel lymph node. In patients with palpable LN, 13
      sentinel lymph nodes were identified. Ten of them were MM involved. Furthermore,
      82 LN were harvested from involved lymph basins and 30 of them were positive for
      MM. In patients without palpable LN, 14 sentinel lymph nodes were identified (3
      positives and 11 negatives for MM) and other 76 LN were resected (all of them
      negative). There were not <<skip metastases>> in any patient. These preliminary
      results support the utility of the technique for the diagnosis and
      lymphadenectomy selection in patients without palpable LN but which could be
      involved by micrometastases.

PMID- 9609840
TI  - [Diagnostic usefulness of radioisotope study of nasal mucociliary transport in
      patients with recurrent respiratory infections].
AB  - Mucociliary transport system is thee most primitive and essential airway defense
      mechanisms. Primary ciliary dyskinesia syndrome (PCDS), an inherited recessive
      autosomal disease, produces an absence of mucociliary transport, therefore
      chronic upper and lower airways infections since birth. The study of nasal
      mucociliary transport by Seroalbumin-Tc99m method is very useful in the diagnosis
      of this syndrome. According to our experience, mucociliary stasis in a patient
      with chronic respiratory airways infections is a typical condition of PCDS.
      Normal nasal mucociliary transport velocity discards the PCDS.

PMID- 9609841
TI  - [Integration of multimodal medical images].
AB  - Multimodality analysis is becoming a required tool in medical practice due to the
      development of different image techniques and new imaging processing tools. This
      paper is a review of the basis of medical image integration, image fusion
      techniques, and their clinical applications, especially addressing our experience
      with brain tomographic studies in nuclear medicine and radiology.

PMID- 9609842
TI  - [Reversible hyperparathyroid metabolic osteopathy secondary to parathyroid
      carcinoma].
AB  - Parathyroid carcinoma is a rare cause of hyperparathyroidism and metabolic
      osteopathy. The authors report a patient with parathyroid carcinoma who underwent
      99mTc-Sestamibi parathyroid and 99mTc-MDP bone scanning. These techniques showed
      the parathyroid lesion and typical features of severe metabolic osteopathy
      respectively. The bone scan performed at only four months after surgery showed
      near complete resolution.

PMID- 9609843
TI  - [Normally functioning ectopic thyroid in adults. Apropos of 4 cases].
AB  - Four cases are presented of ectopic thyroid tissue in adult women who underwent
      for thyroid study for different motives. Radioisotopic uptake was absent in the
      usual thyroid location. Thyroid function was normal in every case and no
      psychomotor abnormalities were present. In one case, echography revealed an
      atrophic thyroid in the usual location in association with thyroid ectopy. The
      literature of thyroid ectopy was reviewed and the preponderant role of
      radioisotopic scan is underlined, together with thyroid echography in the imaging
      diagnosis of neck masses.

PMID- 9609844
TI  - [Thoracic SPECT using (111 In-DTPA-D-Phe1)-octreotide in bronchial carcinoid
      syndrome].
AB  - We describe two cases of bronchial carcinoid tumour detected by (111In-DTPA-D
      Phe1)-octreotide scintigraphy. The SPECT of the thoratic region provided a better
      images of the primary tumour than the planar images. In one of the patients, the
      bronchial carcinoid tumour was associated with sarcoidosis, which led to an
      erroneous evaluation of the extension of the tumour.

PMID- 9609845
TI  - [Study of myocardial viability by positron emission tomography].

PMID- 9609846
TI  - Another way to enhance SOAP's usefulness.

PMID- 9609848
TI  - The role surgery residents in educating medical students.

PMID- 9609847
TI  - Assessing teachers' effectiveness in a pathology course.

PMID- 9609849
TI  - A standardized curriculum and evaluation system for an ophthalmology residency.

PMID- 9609850
TI  - Keeping the faith.

PMID- 9609851
TI  - Sustaining the structure of the professional self.

PMID- 9609852
TI  - On the commodification of medicine.
AB  - The author reviews key themes of medicine and medical education in the 20th
      century, such as the revolution in therapies and the consequent and continuing
      changes in the economics of health care; workforce issues, including the
      controversy over the optimum number of residency slots; and the impact of managed
      care on teaching hospitals and medical schools. This impact is part of "the
      commodification of health care," in which health care is beginning to be bought
      and sold in a market, where prices determine outcomes, and where the not-for
      profit, service orientation of health care providers is threatened. He discusses
      in detail the pressures this new health care environment places on medical
      schools and teaching hospitals, and recounts the first Senate Finance Committee
      hearing in April 1994 on the subject of academic health centers under health care
      reform. Soon after, the Committee approved legislation to create the Graduate
      Medical Education and Academic Health Center Trust Fund, to be financed by a 1.5%
      tax on private health care premiums in addition to Medicare Graduate Medical
      Education payments. The provision was later dropped from a similar bill that came
      before the full Senate, but has since been introduced as the Medical Education
      Trust Fund Act of 1997. The author concludes by cautioning that matters will grow
      more difficult in the near future, since the threats to academic medicine's
      institutions have not yet become part of the national political agenda.

PMID- 9609853
TI  - Revitalization of the Warren G. Magnuson Clinical Center at the National
      Institutes of Health.
AB  - For nearly 45 years the Warren G. Magnuson Clinical Center has been the site of
      the intramural clinical research of the National Institutes of Health. It has
      served as the largest clinical research facility for the nation and the site for
      training many of the clinical investigators in the nation's academic medical
      centers. Research at the Clinical Center has focused on study of orphan diseases
      and phase 1 and 2 clinical trials, and this research emphasis has made it a
      special national resource. Over the last decade there has been a dramatic decline
      in the number of patients seen at the Clinical Center, as well as a perceived
      decrease in the quality of research performed at the center. The decreased
      activity is related in part to fiscal constraints and the impact of the changing
      health care delivery system. The trends at the Clinical Center are particularly
      distributing because they parallel what is happening at academic health centers
      across the country. Because its success is viewed as vital to national clinical
      research, a major effort has been undertaken to revitalize the center. This paper
      reports on the plans and activities undertaken to reorganize the center's
      management, revitalize its infrastructure for conducting clinical research,
      establish vital clinical research training, and promote partnerships with
      extramural investigators who will benefit from access to the center. The hope is
      that the model established at the NIH Clinical Center will assist in the
      revitalization of clinical research across the nation.

PMID- 9609854
TI  - Anonymity and pseudonymity in whistleblowing to the U.S. Office of Research
      Integrity.
AB  - Given the concerns expressed by members of the academic and legal community about
      whether (and how) to handle anonymous and pseudonymous allegations of scientific
      misconduct, this paper summaries the experiences of the Office of Research
      Integrity and its predecessor from 1989 through 1997. Although the record shows
      that research institutions and the ORI have treated such allegations seriously,
      the fraction of complainants to the ORI who remain anonymous is small (8% of 986
      allegations); few anonymous complaints are sufficiently substantive to be pursued
      (4% of the 357 formal cases opened in the ORI); and only 1 of these 13 cases
      resulted in an ORI finding of scientific misconduct.

PMID- 9609855
TI  - Songs of innocence and experience: student's poems about their medical education.
AB  - Personal creative writing is increasingly used in medical schools to foster self
      reflection. This article looks particularly at poetry as a vehicle for expressing
      personal experiences of professional development. The authors present a series of
      poems written by students at their medical school. In them, the students reflect
      on embryology, gross anatomy, telling (or not telling) bad news to trusting
      patients (and family members), encountering death, and encountering their own
      anger and frustration with the demands of medicine. These poems not only capture
      individual students' feelings and imaginations but also demonstrate the students'
      constant struggle to sustain their idealism about medicine throughout the four
      years of their education.

PMID- 9609856
TI  - Educating residents for managed care: report on a multidisciplinary conference.
AB  - A growing number of residency programs are preparing their graduates for the
      realities of managed care practice. In 1996, The Cleveland Clinic Foundation, a
      private, nonprofit academic medical center, hosted a two-day conference on
      managed care education to develop innovative instructional and evaluative
      approaches that, where appropriate, would build on existing expertise. The
      conference was attended by invited national experts who had a stake in residents'
      education: clinical faculty, residents, medical educators, executives of managed
      care organizations, and representatives of other interested organizations.
      Participants spent much of their time in four small break out groups, each
      focusing on one of the following topics that were judged particularly relevant to
      managed care: preventive and population-based medicine, appropriate utilization
      of resources, clinician-patient communication, and interdisciplinary team
      practice. Participants shared existing materials, discussed teaching goals and
      objectives, and generated ideas for teaching methods, teaching materials, and
      evaluative methods for their respective topics. The authors summarize the
      recommendations from the four groups, with an overview of the issues that emerged
      during the conference concerning curriculum development, integration of managed
      care topics into existing curricula, staging of the curriculum, experiential
      teaching methods, negative attitudes and resistance, evaluation of trainees and
      profiling, program assessment, faculty development, and cooperation between
      academic medical centers and managed care organizations.

PMID- 9609857
TI  - How a community teaching hospital is changing to better serve its community.
AB  - In recent years increased attention has been focused on the importance of
      teaching hospitals' serving the health of their communities. A community teaching
      hospital may have a special impetus and some advantages because of its linkage to
      a defined geographic community and a traditional mission of providing clinical
      and other services to that community. The authors describe how their community
      teaching hospital, the health and education services network it belongs to, and
      the integrated delivery system of which it is a member work together to respond
      to the current challenge to provide care and education to local communities. In
      particular, they describe how since 1995 the hospital has used an approach
      (called Measurably Enhancing the Status of Health) to create and operate its new
      Department of Community Health and Health Studies and associated new programs to
      benefit the community. The new department combines innovative community outreach
      programs with an emphasis on the qualitative and quantitative evaluation of the
      these programs. There are also programs of medical education in the hospital and
      at the Pennsylvania State University College of Medicine, and other programs that
      have community educational components (e.g., a coalition to reduce the number of
      smokers; a center to reduce health risks and prevent disease). The authors and
      their hospital colleagues have found three concepts to be helpful as they reflect
      on what they have learned since 1995 and continue to refine their community
      outreach work: community, complexity, and collaboration/competition. They explain
      these concepts and suggest that other institutions in academic medicine may find
      them and the ideas and programs of their hospital useful as the seek ways to care
      for, educate, and measure the health status of their own communities.

PMID- 9609858
TI  - Sustaining curricular change at Sherbrooke through external, formative program
      evaluations.
AB  - In this case study, the authors discuss external, formative program evaluation as
      a means to monitor and sustain ongoing curricular change and to prepare for
      periodic accreditation reviews. The Faculty of Medicine at Sherbrooke (in Quebec,
      Canada), following a major curricular reform begun in the mid-1980s, held three
      external, formative program evaluations in 1988, 1991, and 1994, using expert
      judgment and "connoisseur" models of evaluation. The authors present the goals of
      the evaluations (e.g., to evaluate the implementation of intended curricular
      changes) and the 17-step process used (e.g., "involve as many faculty and
      students as possible before and during the visit"), and describe the preparation
      for the evaluations, the selection of the external evaluators (e.g., a chief
      medical officer from the World Health Organization, a high-profile basic sciences
      teacher, the chairman of the previous accreditation team, and others), and on
      site activities and reporting. Recommendations from the evaluators and the
      subsequent actions taken (and in a few cases, not taken) by the school are
      presented and discussed in terms of program planning, curricular content, basic
      sciences, problem-based learning and tutors' training, assessment of students,
      resource constraints, clerkships, community orientation, students' self
      directedness, and medical humanism. The three evaluations helped guide and
      support the major curricular undertakings and encouraged continued changed and
      refinements. They also had a significant effect on the curriculum itself, on the
      faculty, and on the socioeducational climate of the school.

PMID- 9609859
TI  - "Reform without change": update, 1998.
AB  - As a result of the Flexner Report in 1910, proprietary medical schools
      disappeared and science taught by researchers became a part of every medical
      school curriculum. Medical research produced products that improved health and
      brought large profits to health-related industries. Research became the currency
      most valued within the organizational power structure of medical schools,
      overshadowing the educational mission. Almost 90 years and multiple calls for the
      educational reform of medical education have failed to bring about true change in
      medical education because of researchers' conflict of interest--that is, the time
      spent providing effective education equals time away from the research necessary
      to maintain their careers. Basic scientists have kept teaching in medical schools
      efficient by giving discipline-related lectures that allow them to maximize their
      research time. Planning for meaningful learning with integration of disciplines
      and small-group teaching requires an investment of time that researchers are
      unwilling to make because it does not further their careers. Separation of
      scientific research from medical school teaching is necessary for reform of
      medical education. Medical students need to be taught by teachers who are not
      researchers.

PMID- 9609860
TI  - Old thoughts, new ideas: comparing traditional Talmudic education with today's
      medical education.
AB  - The authors compare innovative learning strategies in medical education today
      with the traditional educational methods of Jewish Talmudic study. These methods
      began to be developed in yeshivas (the highest Jewish educational institutions)
      in the third century BC and continue to be used in yeshivas today. The teaching
      in thousands of yeshivas of Talmudic study worldwide emphasizes student-centered,
      problem-based, small-group, and lifelong learning. Further, in the yeshivas rote
      memorization is discouraged; students are selected on the basis of merit rather
      than social status; and the teachers (particularly master teachers) are expected
      to act as role models for all aspects of living. Over the centuries, the yeshiva
      has been slightly modified and specialized, and the number of students has
      increased, but the institution has retained its basic instructional format. The
      authors briefly describe each aspect of Talmudic study and how it relates to
      current educational practices in medical schools. They argue that comparing these
      two educational institutions--the yeshiva and medical school--is valuable, in
      that the history of the yeshiva educational system, which has successfully
      produced generations of creative scholars, educators, and leaders, as well as an
      enormous body of literature, validates the innovative teaching approaches being
      used in medical schools today.

PMID- 9609861
TI  - What are we going to do with all that money?

PMID- 9609862
TI  - Medicare provider-sponsored organizations: opportunities and challenges.

PMID- 9609863
TI  - Clarifying the relationship of medical education and moral development.
AB  - PURPOSE: To assess the development of the moral reasoning skills of medical
      students through the course of their education, and to determine whether their
      scores would reflect the increases usually found at this age range and education
      level. METHOD: Using Rest's Defining Issues Test (DIT), the authors assessed the
      moral reasoning of a total of 95 Texas A&M medical students from the classes of
      1991-94 at the beginning of their first semester, at the end of a required first
      semester medical ethics course, and at the end of the students' fourth year.
      RESULTS: The mean score on the first test was 47.7; on the second, 53.7; and on
      the third, 56.5. The +6.0 change in mean scores from the first to second test was
      statistically significant (p < .0001), as was the +8.8 change from the first to
      final test (p < .0001). The +2.8 change from the second to final test was also
      significant, although at a lower level (p < .0302). Analysis revealed no
      significant correlation between moral reasoning scores and age; however, there
      was a significant correlation between moral reasoning scores and sex, with women
      scoring higher than men on all three tests. CONCLUSIONS: While data from the
      current study seem to contradict earlier findings that medical education inhibits
      an increase in moral reasoning skills, the current findings may alternatively be
      interpreted as resulting mainly from the required first-semester medical ethics
      course, which involved small-group discussion of moral dilemmas, an educational
      method shown elsewhere to be effective in enhancing moral reasoning skills.

PMID- 9609864
TI  - The amount of small-group case-study discussion needed to improve moral reasoning
      skills of medical students.
AB  - PURPOSE: To examine how much exposure to small-group case-study discussion is
      necessary to significantly increase moral reasoning skills. METHOD: For the
      classes of 1991-1998 at Texas A&M, using Rest's Defining Issues Test, the authors
      tested groups of students for moral reasoning skills both before and after the
      students participated in small-group case-study discussions of medical ethics.
      RESULTS: From 960 students asked to participate, the authors collected complete
      data for 729 students (75.9% response rate). Small-group case-study exposures
      ranged from 0 to 44 hours. Groups of students exposed to 20 hours or more
      demonstrated a significant increase in their moral reasoning scores. Groups with
      less than 20 hours of exposure demonstrated no significant increase in their
      scores. CONCLUSION: This study indicates that moral reasoning skills are
      teachable and measurable, and that small-group discussion significantly increases
      moral reasoning skills. Further studies are needed to increase the
      generalizability of these findings.

PMID- 9609865
TI  - Injury-control education in six U.S. medical schools.
AB  - PURPOSE: To assess knowledge, attitudes, and formal instruction related to injury
      control among fourth-year medical students. Injury is the leading cause of death
      among Americans aged 1 to 44 years. METHOD: The authors conducted a cross
      sectional survey of fourth-year students at six U.S. medical schools, four of
      which maintain federally funded injury prevention research centers. Main outcome
      measures included injury-related knowledge scores, three attitude measures, and
      self-reported exposures to injury prevention education. RESULTS: Six hundred and
      thirty-five fourth-year medical students (73% of those eligible) participated.
      The responding students were, on average, unable to correctly answer half of the
      questions testing injury-related knowledge. They rated medical problems more
      important and more preventable than injury problems, and they felt more
      comfortable asking their patients about risk factors for medical problems. These
      findings may be explained, in part, by the students' reported minimal exposure to
      injury control education in medical school. The students encountered the topic
      more frequently on rotations in pediatrics (84%), family medicine (73%), and
      preventive medicine (66%) than on rotations in emergency medicine (47%), internal
      medicine (41%), or obstetrics and gynecology (34%). Injury control was
      encountered least often on rotations in psychiatry (23%) and surgery (14%).
      CONCLUSIONS: These findings suggest that injury control is given limited coverage
      in the curricula of U.S. medical schools. As a result, students have little
      understanding of the principles and benefits of injury control.

PMID- 9609866
TI  - Medical students' perceptions of unethical conduct at one medical school.
AB  - PURPOSE: To assess medical students' perceptions of the ethical environment
      across four years of medical school. METHOD: In the spring of 1996, the authors
      distributed a questionnaire to all four classes at the Wake Forest University
      School of Medicine. The students provided demographic information and information
      about their exposures to or participation in unethical situations. Results were
      analyzed using multiple analysis of variance, univariate analysis of variance,
      Pearson correlation, and cross-tabulations. RESULTS: The response rate was 71%.
      The students reported that exposures to unethical behavior started early and
      continued to increase with each year in school. For example, 35% of the first
      year students reported observing unethical conduct by residents or attending
      physicians. This percentage rose to 90% of the fourth-year students. The authors
      found no significant relationship between demographic variables other than the
      year in school and the ethical dilemma variables. CONCLUSION: Medical students
      face perceived ethical dilemmas beginning as early as the first year of medical
      school. Thus ethics instruction must begin in the freshman year. In addition,
      there must be changes to the environment in which clinical education is conducted
      to enhance the positive enculturation of students into the medical profession.

PMID- 9609867
TI  - Misrepresentation of authorship by applicants to pediatrics training programs.
AB  - PURPOSE: To determine whether applicants to pediatrics residency and fellowship
      programs misrepresented authorship of publications. METHOD: The authors sampled
      1995 applications to the University of Washington School of Medicine's pediatrics
      residency program and pediatrics pulmonary fellowship program. They submitted all
      publications claimed in the submitted applications to extensive efforts to
      authenticate both their existence and authorship. RESULTS: Among the 404
      pediatrics residency program applications studied, 147 claimed authorship of
      publications; 29 (19.7%) of these contained at least one unverifiable
      publication. Of the 401 publications claimed in the 147 applications, 41 (10.2%)
      could not be confirmed. Among 31 fellowship applications, 14 claimed
      publications. At least one citation was unverifiable for each of the 14
      applications. Of the total 77 publications claimed, 31 (40%) could not be
      confirmed. CONCLUSION: Misrepresentation occurs on graduate medical education
      applications; solutions are needed to address this problem.

PMID- 9609868
TI  - Poison pen letters, due process, and medical schools' policies toward anonymous
      correspondence that disparages medical school faculty.
AB  - PURPOSE: To learn more about the frequency of and response to poison pen letters
      (anonymous correspondence that disparages faculty members) in academic medicine.
      METHOD: The authors surveyed all 143 deans of medical schools that are members of
      the AAMC about their practices and policies regarding the handling of poison pen
      letters. RESULTS: Of the deans surveyed, 119 (83%) responded. Sixty-seven deans
      (56%) reported having received poison pen letters during their tenure. Of those,
      16 (24%) reported that they had discarded the letters based solely on the
      anonymity of the authors. The remaining 51 deans (76%) reported that they had
      either sequestered, investigated, or placed the letters into the faculty members'
      files, or that they had based their decisions to discard the letters on factors
      other than the authors' anonymity. Only one dean reported having a written policy
      for handling such correspondence. CONCLUSION: This survey of AAMC schools
      indicates that poison pen letters are not uncommon. The authors recommend a
      policy by which anonymous letters that disparage current or prospective faculty
      members would be categorically discarded.

PMID- 9609869
TI  - Using natural frequencies to improve diagnostic inferences.
AB  - PURPOSE: To test whether physician's diagnostic inferences can be improved by
      communicating information using natural frequencies instead of probabilities.
      Whereas probabilities and relative frequencies are normalized with respect to
      disease base rates, natural frequencies are not normalized. METHOD: The authors
      asked 48 physicians in Munich and Dusseldorf to determine the positive predictive
      values (PPVs) of four diagnostic tests. Information presented in the four
      problems appeared either as probabilities (the traditional way) or as natural
      frequencies. RESULTS: When the information was presented as probabilities, the
      physicians correctly estimated the PPVs in only 10% of cases. When the same
      information was presented as natural frequencies, that percentage increased to
      46%. CONCLUSION: Representing information in natural frequencies is a fast and
      effective way of facilitating diagnosis insight, which in turn helps physicians
      to better communicate risks to patients, and patients to better understand these
      risks.

PMID- 9609870
TI  - Emotional and cognitive empathy in medical schools.

PMID- 9609871
TI  - Effect of inclusion of cost information on student and faculty evaluation of a
      computer-assisted, problem-based learning course.

PMID- 9609872
TI  - On the importance and validity of medical accreditation standards.
AB  - In late 1997, the authors conducted a national survey of communities of interest
      about the importance and clarity of 44 accreditation standards applied to
      teaching, learning, and evaluation in medical schools by the Liaison Committee on
      Medical Education (LCME). Questionnaires were mailed to deans and educational
      administrators at U.S. medical schools; current LCME members and surveyors and
      those who had served during the preceding five years; a random selection of
      residency program directors drawn from both general practice and speciality
      disciplines; sample groups of medical students and residents; and a cohort of
      practicing physicians not affiliated with academic medical institutions.
      Altogether 1,659 questionnaires were mailed, and 701 responses were received
      (42%). The recipients were asked to use a five-point Likert scale to rate each of
      the 44 standards both for its perceived importance as an indicator of the quality
      of undergraduate medical education and for the clarity with which the standard's
      intent was conveyed. Although the mean ratings of importance all fell in the
      "moderately important" and "highly important" areas across the respondent groups,
      the ratings divided into three groups, semantically and statistically. At the
      high end for importance are standards dealing with fundamental qualities of
      students, instruction, and the structuring of resources. At the low end of the
      importance scale are standards dealing largely with matters of process. The
      ratings for clarity were systematically lower than the ratings for importance,
      and in some cases the rating for clarity were even more widely discrepant with
      the ratings for importance. Individual comments by respondents about certain
      standards were critical of their complicated construction and of confusion about
      their meaning and measures of compliance. One or more of these hallmarks--being
      rated of lower importance or clarity, and being the target of criticism by survey
      respondents--distinguished most of the standards that earlier study had shown are
      often neglected by surveyors. The predictive validity of each of a number of
      standards was examined by testing the association between the standard (or its
      derivative) and outcomes expressed in annual student and school questionnaires
      and compiled in databases of the Association of American Medical Colleges and the
      American Medical Association. The result was a mixed bag, confounded by the
      absence of specific dimensions of many accreditation standards (independent
      variables) and the lack of discriminating measures of outcome (dependent
      variables). Nevertheless, the LCME's accreditation standards are believed to be
      important by those most affected by them. And beyond validating that medical
      accreditation is guided by relevant standards for teaching, learning, and
      evaluation, the results of this study point to ways by which the process can be
      made more precise and useful.

PMID- 9609873
TI  - The Society of Computed Body Tomography and Magnetic Resonance Imaging. Research
      in CT and MR imaging: 2000 and beyond.

PMID- 9609874
TI  - Dialysis Outcomes Quality Initiative: required reading for radiologists.

PMID- 9609875
TI  - Should cutting needles replace needle aspiration of lung lesions?

PMID- 9609876
TI  - Blunt carotid injury: a review.

PMID- 9609877
TI  - Yasargil aneurysm clips: evaluation of interactions with a 1.5-T MR system.
AB  - PURPOSE: To evaluate the magnetic field interactions with Yasargil aneurysm clips
      exposed to a 1.5-T MR system. MATERIALS AND METHODS: Sixteen Yasargil aneurysm
      clips made with Phynox (10 clips returned to the manufacturer due to suspected
      magnetic field interactions and six clips obtained from the manufacturer in
      sterile packages) were tested for magnetic field interaction at 1.5 T by using
      techniques to assess magnetic field-induced translational (deflection angle test)
      and torque (changes in alignment or rotation) forces. RESULTS: None of the
      aneurysm clips demonstrated magnetic field interactions; that is, deflection
      angles were zero and there were no changes in alignment or evidence of rotational
      forces present. CONCLUSION: It is safe to perform MR procedures at 1.5 T or less
      in patients with Yasargil aneurysm clips made with nonferromagnetic material.

PMID- 9609878
TI  - MR imaging of the mamillothalamic tract.
AB  - PURPOSE: To demonstrate the normal and abnormal appearance of the mamillothalamic
      tract (MTT) on cranial magnetic resonance (MR) images. MATERIALS AND METHODS: Two
      formalin-fixed normal human brain specimens sectioned in axial and coronal planes
      were used to demonstrate the normal anatomy of the MTT. MR images were obtained
      in 32 volunteers. Proton-density-weighted coronal and axial pulse sequences were
      used. The images were evaluated for visualization quality and size and signal
      intensity of the MTTs in correlation with the specimens. Abnormal MTTs were
      identified on cranial MR images in two patients, and the imaging findings were
      analyzed. The clinical history of the patients was also reviewed to determine the
      effect of these findings on patient care. RESULTS: Normal MTTs were easily
      identified on MR studies of cadaveric brains and of the brains of the human
      volunteers. On MR images, normal MTTs were commonly symmetric in appearance, with
      signal intensity equal to that of other normal fiber tracts. The abnormal MTTs
      showed high signal intensity on images obtained with a long repetition time or
      asymmetric volume loss and were associated with atrophy of the ipsilateral
      mamillary body. CONCLUSION: Normal MTTs are readily visible on conventional MR
      images. Abnormality of the MTT is a very subtle finding but may be a marker of a
      limbic system abnormality.

PMID- 9609879
TI  - The caput medusae sign.

PMID- 9609880
TI  - Cerebral vasculopathy and neurologic sequelae in infants with cervicofacial
      hemangioma: report of eight patients.
AB  - PURPOSE: To determine the association of cerebral arterial anomalies and
      progressive cerebral arterial occlusive disease in infants with facial
      hemangiomas. MATERIALS AND METHODS: The cases of eight infants (seven girls and
      one boy) with the diagnosis of cervicofacial hemangioma and intracranial arterial
      anomalies were reviewed retrospectively. Findings from clinical and imaging
      examinations--including cranial computed tomography, magnetic resonance imaging
      and angiography, and catheter angiography--were evaluated. Serial imaging
      findings were studied to document progressive intracranial vascular changes.
      RESULTS: Five patients had additional associated congenital anomalies. Seven were
      treated with corticosteroids, interferon alfa-2a, or both. Progressive
      cerebrovascular occlusive changes were documented in four of the seven patients
      with serial imaging findings. Four other patients (all treated pharmacologically)
      had MR imaging documentation of cerebral infarction, and all had consistent,
      acquired neurologic symptoms. CONCLUSION: Intracranial arterial anomalies can
      coexist with cervicofacial hemangioma. Aneurysmal and occlusive changes are
      potentially progressive and can result in cerebral infarction. A causative
      association between occlusive cerebrovascular disease and pharmacologic treatment
      has not been excluded.

PMID- 9609881
TI  - Subdural empyema in 10 infants: US characteristics and clinical correlates.
AB  - PURPOSE: To investigate the ultrasonographic (US) characteristics of subdural
      empyema (SDE) and its differentiation from reactive subdural effusion (RSE) in
      infants with meningitis. MATERIALS AND METHODS: Images in 10 infants with SDE
      with or without RSE complicating meningitis were retrospectively reviewed and
      correlated with clinical findings and compared with US and magnetic resonance
      (MR) images in four infants with meningitis and RSE. RESULTS: At US, 15 of 16
      SDEs in the 10 infants were seen as heterogeneous to hyperechoic convexity
      collections. Hyperechoic strands were seen in 12 SDEs. Other findings included a
      thick, echogenic inner membrane (n = 9), increased echogenicity of pia-arachnoid
      and exudates in the subarachnoid space (n = 16), mass effect (n = 16), and
      loculated extraaxial collections (n = 2). MR imaging findings correlated well
      with US and surgical results. At computed tomography, SDE was misinterpreted as
      RSE in one patient, due to the absence of inner membrane contrast material
      enhancement. Clinical outcome was related to the degree of brain damage
      consequent to meningitis and the chronicity of SDE. RSEs in seven infants (three
      with concurrent SDE) were anechoic; an inner membrane was seen in six, and
      increased pia-arachnoid echogenicity was seen in four. CONCLUSION: SDE has
      complex US features that are helpful for differentiation from anechoic RSE in
      infants with meningitis.

PMID- 9609882
TI  - Review of 3,530 referrals for bone density measurements of spine and femur:
      evidence that radiographic osteopenia predicts low bone mass.
AB  - PURPOSE: To determine the relationship between bone mineral density (BMD)
      measurements and the initial reason for referral to a BMD screening service.
      MATERIALS AND METHODS: Referral letters for 3,479 of the 3,530 women referred for
      BMD screening were classified according to the indication for screening. Mean age
      matched standard deviation scores (Z scores) were derived for each of the 10 most
      common indications. Mean BMD between each group was compared with the age-matched
      value from the local normal range by means of a one-sample Student t test. Mean
      young normal standard deviation scores (T scores) were derived, and the
      percentages of women with osteopenia or osteoporosis from each referral group
      were calculated on the basis of the World Health Organization criteria. RESULTS:
      The most common reason for referral was to aid in a decision regarding hormone
      replacement therapy (n = 700). The highest proportion of women with osteoporosis
      in any group was in the radiographic osteopenia group (n = 269). CONCLUSION:
      Radiographic evidence of osteopenia is a strong predictor of osteoporosis.
      Screening for osteopenia appears justified in this and other high-risk groups and
      those seeking a rationale for preventive therapy.

PMID- 9609883
TI  - Osteomyelitis of the foot: relative importance of primary and secondary MR
      imaging signs.
AB  - PURPOSE: To determine the usefulness of primary and secondary magnetic resonance
      (MR) imaging signs of osteomyelitis. MATERIALS AND METHODS: MR imaging at 1.5 T
      was performed in 73 feet (62 patients) with clinical concern for osteomyelitis.
      Images were reviewed retrospectively and separately by two reviewers in a blinded
      fashion for primary (abnormal marrow signal intensity) and secondary (ulcer,
      cellulitis, soft-tissue mass, abscess, sinus tract, cortical interruption) signs
      associated with osteomyelitis. RESULTS: Of the 73 feet, 43 had osteomyelitis.
      Discordant marrow signal intensity between individual MR sequences was observed
      by reader 1 in six (8%) feet and by reader 2 in 15 (21%) feet. For primary signs,
      fast spin-echo short inversion time inversion-recovery and gadolinium-enhanced
      fat-suppressed T1-weighted images had the highest sensitivity, and T1-weighted
      and gadolinium-enhanced fat-suppressed T1-weighted images had the highest
      specificity and least interobserver variability. Signs of cutaneous ulcer, sinus
      tract, and cortical interruption had the highest positive predictive value for
      osteomyelitis; signs of soft-tissue mass and cortical interruption had the
      highest negative predictive value. All had good interobserver agreement except
      cellulitis. CONCLUSION: When osteomyelitis of the foot is suspected, marrow
      signal intensity can differ on different types of MR images. Identification of
      secondary signs may augment diagnostic confidence when abnormal marrow signal
      intensity is seen.

PMID- 9609884
TI  - Internal derangements of the knee: rates of occurrence at MR imaging in patients
      referred by orthopedic surgeons compared with rates in patients referred by
      physicians who are not orthopedic surgeons.
AB  - PURPOSE: To compare the occurrence at magnetic resonance (MR) imaging of
      clinically important knee abnormalities in patients referred by orthopedic
      surgeons with that in patients referred by other physicians. MATERIALS AND
      METHODS: Knee MR images in all patients referred for evaluation of internal
      derangement for 12 months were retrospectively reviewed. Meniscus, ligament, and
      articular cartilage abnormalities were tabulated. The numbers of abnormalities
      detected in the patients referred by orthopedic surgeons were compared with those
      in the patients referred by all other physicians by using chi(2) analysis.
      Significance was defined at P less than .05. RESULTS: Knee MR images in 439
      patients were reviewed; 328 patients were referred by orthopedic surgeons, and
      111 were referred by other physicians. There was no significant difference in the
      rates of occurrence of meniscus tear (149 [45%; orthopedic surgeon referrals] vs
      50 [45%; other physician referrals], P = .96); ligament tear (82 [25%] vs 21
      [19%], P = .25); isolated hyaline cartilage defect (77 [23%] vs 20 [18%], P =
      .29); meniscus or ligament tear (167 [51%] vs 55 [50%], P = .86); or meniscus,
      ligament, or articular cartilage tear (242 [74%] vs 72 [65%], P = .34). The
      proportion of patients who subsequently underwent surgery of the knee was also
      similar (39% [118 of 300] vs 28% [23 of 82], P = .14). CONCLUSION: There was no
      significant difference in the occurrences of clinically important knee internal
      derangement at MR imaging between patients referred by orthopedic surgeons and
      those referred by other physicians.

PMID- 9609885
TI  - Developing epiphysis: MR imaging characteristics and histologic correlation in
      the newborn lamb.
AB  - PURPOSE: To correlate magnetic resonance (MR) signal characteristics of
      developing regions at the ends of bones with the histologic findings. MATERIALS
      AND METHODS: In 36 newborn lamb epiphyses (including cartilage of the epiphysis
      and physis, and bone of the secondary ossification center and juxtaphyseal
      metaphysis), signal intensity and thickness of cartilaginous regions seen on MR
      images were correlated with architecture and thickness of zones shown in
      corresponding histologic sections. Possible effects of T2, magnetization
      transfer, fat or water content, chemical shift, and anisotropy on differences in
      regional signal intensity were evaluated. RESULTS: MR imaging depicted five
      regions between the secondary ossification center and the metaphysis
      corresponding histologically to (a) zone of provisional calcification of the
      secondary ossification center, (b) physis of the secondary ossification center,
      (c) epiphyseal cartilage, (d) physis, and (e) zone of provisional calcification.
      The thickness of regions shown on T1- and T2-weighted images correlated with that
      of histologic zones (r = .9). T2 signal intensity and relaxation time were
      greater in physeal than in epiphyseal cartilage (P < .01). No regional
      differences due to fat or water content, magnetization transfer, chemical shift,
      or anisotropy were found. CONCLUSION: MR imaging findings differentiate
      epiphyseal and physeal regions and correlate with histologic findings. T2 is
      slower in physeal than in epiphyseal cartilage, probably reflecting differences
      in water binding.

PMID- 9609886
TI  - Aortic and hepatic contrast medium enhancement at CT. Part I. Prediction with a
      computer model.
AB  - PURPOSE: To develop a physiologic model of contrast medium enhancement by
      incorporating available physiologic data and contrast medium pharmacokinetics and
      to predict organ-specific contrast medium enhancement at computed tomography (CT)
      with various contrast medium injection protocols in patients of variable height
      and weight. MATERIALS AND METHODS: A computer-based, compartmental model of the
      cardiovascular system was generated by using human physiologic parameters and
      more than 100 differential equations to describe the transport of contrast
      medium. Blood volume, extracellular fluid volume, and regional blood flow were
      estimated from available data. Local structures were modeled mathematically to
      describe the distribution and dispersion of intravascularly administered
      iodinated contrast medium. A global model was formed by integrating regional
      circulation parameters with the models of local structures. Aortic and hepatic CT
      contrast-enhancement curves were simulated for three protocols and were compared
      with mean enhancement curves in three groups of 25-28 patients (80 patients
      total; 28 in one group, 25 in one group, and 27 in one group) receiving the same
      protocols. The percent difference in maximum enhancement between the simulated
      and empiric curves and the enhancement difference index (sum of the area
      difference between the simulated and empiric curves divided by the total area
      under the empiric curve) were computed. RESULTS: The simulated and empiric
      enhancement curves closely agreed in maximum enhancement (the mean percent
      difference in the aorta was 7.4%; liver, 4.8%) and in variation over time (mean
      enhancement difference index in the aorta was 11.6%; liver, 12.7%). CONCLUSION: A
      computer-based, physiologic model that may help predict organ-specific CT
      contrast medium enhancement for different injection protocols was developed. Such
      a physiologic model may have many clinical applications.

PMID- 9609887
TI  - Aortic and hepatic contrast medium enhancement at CT. Part II. Effect of reduced
      cardiac output in a porcine model.
AB  - PURPOSE: To investigate how reduction in cardiac output affects the magnitude and
      timing of aortic and hepatic contrast medium enhancement during abdominal
      computed tomography (CT). MATERIALS AND METHODS: Eight 20-30-kg pigs underwent CT
      before and after pharmacologic reduction of cardiac output (measured by means of
      thermodilution). Each CT study consisted of 53 dynamic images acquired every 5
      seconds at a fixed level through the midliver after intravenous injection of
      contrast medium (concentration, 282 mg of iodine per milliliter; dose, 2 mL per
      kilogram of body weight; injection rate, 2 mL/sec). Curves of contrast medium
      enhancement versus time were measured. Changes in the magnitude and timing of
      aortic and hepatic enhancement were compared with the reduction in cardiac
      output. RESULTS: With reduction in cardiac output, the time from the injection
      start to the arrival of the contrast medium bolus in the aorta (P < .01) and the
      times from injection completion to peak aortic (P < .01) and peak hepatic (P <
      .01) enhancement increased. As cardiac output decreased, peak aortic enhancement
      increased proportionally (P < .01). Peak hepatic enhancement increased only
      slightly and correlated weakly with the decrease in cardiac output (P = .07).
      CONCLUSION: As cardiac output decreases, the times to the arrival of the contrast
      medium bolus in the aorta and to peak aortic and hepatic enhancement increase.
      Reduction in cardiac output results in a substantial increase in peak aortic
      enhancement but not in peak hepatic enhancement.

PMID- 9609888
TI  - Improvement in mammography quality control: 1987-1995.
AB  - PURPOSE: To assess possible changes in quality control (QC) practices at
      mammography sites in the United States. MATERIALS AND METHODS: Mammography site
      surveys were conducted in 1990, 1992, and 1995 through the Colorado Mammography
      Advocacy Project (CMAP). Data from mammography sites applying for American
      College of Radiology (ACR) accreditation were collected between August 1987 and
      August 1993 through the ACR Mammography Accreditation Program. Data from both of
      these surveys were analyzed to assess temporal changes in mammography QC
      practices in the United States between 1987 and 1995. RESULTS: CMAP results
      indicated statistically significant improvement in medical physicist QC practices
      between 1990 and 1992 and in technologist QC practices between 1990 and 1995.
      Improvements in radiologic technologist QC practices coincided with increases in
      radiologic technologist continuing education in mammography. ACR results
      indicated statistically significant improvement in technologist QC practices
      between 1988 and 1992. CONCLUSION: There have been substantial improvements in QC
      practices at mammography sites in the United States during the past decade.

PMID- 9609889
TI  - Retroareolar breast carcinoma: clinical, imaging, and histopathologic features.
AB  - PURPOSE: To evaluate the clinical, imaging, and histopathologic features of
      breast carcinoma in the retroareolar tissues and to determine whether there are
      any characteristics common to this location. MATERIALS AND METHODS: Thirty-five
      patients (age range, 38-77 years) with 37 retroareolar carcinomas were identified
      retrospectively. Retroareolar carcinoma was defined as that within 2 cm of the
      nipple-areolar complex. Mammographically occult tumors were identified by using
      histopathologic records (n = 4) or clinical examination findings (n = 6).
      RESULTS: Twenty-nine (78%) tumors had clinical findings, including palpable mass
      (n = 29), associated nipple inversion or retraction (n = 4), and associated
      nipple discharge (n = 2). Twenty-seven (73%) tumors had mammographic findings of
      mass (n = 16), mass with calcifications (n = 5), and microcalcifications (n = 6;
      four of these microcalcifications were associated with a mammographically occult
      palpable mass). Ultrasound was performed in 17 tumors, all of which were
      hypoechoic. The stage of 31 carcinomas was known: one was stage 0, 17 were stage
      I, and 13 were stage II. Histopathologic analysis revealed 35 ductal carcinomas
      and two invasive lobular carcinomas. CONCLUSION: Retroareolar carcinoma usually
      manifests as a palpable mass. Mammography is less sensitive in this area than in
      other areas of the breast. Ultrasound can be a valuable adjunct in the assessment
      of retroareolar malignancy.

PMID- 9609890
TI  - MR imaging of mammographically detected clustered microcalcifications: is there
      any value?
AB  - PURPOSE: To assess the value of dynamic magnetic resonance (MR) imaging in
      patients with mammographically detected suspicious microcalcifications. MATERIALS
      AND METHODS: Sixty-three patients (age range, 31-84 years; mean age, 56 years)
      with mammographically suspicious clustered microcalcifications underwent dynamic
      MR imaging of the breast before surgical biopsy. MR imaging was performed with a
      1.5-T unit and a two-dimensional fast low-angle shot sequence with a flip angle
      of 80 degrees. Thirty-two axial sections, 4 mm thick and without interval gaps,
      were acquired before and five times after administration of gadopentetate
      dimeglumine (dose, 0.1 mmol per kilogram of bodyweight). Histologic findings were
      used as the standard of reference. Any effect of MR imaging on surgical
      management was noted. RESULTS: Biopsy findings verified five patients with T1
      invasive carcinomas, 33 with ductal carcinomas in situ, 13 with proliferative
      fibrocystic disease, eight with nonproliferative fibrocystic disease, and four
      with sclerosing adenosis. Contrast material-enhanced dynamic MR imaging had a
      sensitivity of 45%, a specificity of 72%, and an overall accuracy of 56% in
      differentiating benign from malignant microcalcifications. All invasive tumors
      were detected with MR imaging. In no case was surgical management altered by MR
      imaging findings. CONCLUSION: MR imaging of the breast is not reliable in
      differentiation of benign from malignant breast disease in mammographically
      suspicious clustered microcalcifications and has no effect on treatment.

PMID- 9609891
TI  - Transjugular intrahepatic portosystemic shunt patency and the importance of
      stenosis location in the development of recurrent symptoms.
AB  - PURPOSE: To analyze in detail the location and types of stenosis and occlusion
      that occur after transjugular intrahepatic portosystemic shunt (TIPS) creation
      and to determine the relative contribution of these various types of TIPS
      malfunction to recurrent symptoms of variceal bleeding or ascites. MATERIALS AND
      METHODS: In 116 of 217 patients who underwent TIPS creation between June 1990 and
      July 1995, follow-up portal venography was performed at 6-month intervals and for
      symptoms of recurrent variceal bleeding or ascites. RESULTS: Cumulative primary
      venographic patency by means of Kaplan-Meier survival analysis was 55% at 6
      months and 5% at 2 years. Secondary patency was 92% at 2 years. Stenosis or
      occlusion occurred in 63 of 116 patients (54%). In 20 patients (17%), acute shunt
      occlusions developed less than 30 days after TIPS creation; in 24 patients (21%),
      tract abnormalities were detected after 30 days; and in 19 patients (16%),
      hepatic vein stenoses were detected after 30 days. Abnormalities of the
      parenchymal tract were more often correlated with recurrent variceal bleeding or
      ascites than were hepatic vein stenoses (odds ratio, 3.6; P = .02). Ten of 14
      patients (71%) with detected biliary fistulas to their TIPS had symptoms, and all
      patients with biliary fistulas had tract abnormalities. CONCLUSION: Tract
      stenoses and occlusions were the major cause of symptomatic shunt failure after
      TIPS creation. Substantial bile duct transections are often associated with tract
      abnormalities and recurrent symptoms. Although common, hepatic vein stenoses were
      rarely associated with recurrent symptoms in our patient population.

PMID- 9609892
TI  - Lower extremity: nonstepping digital angiography with photostimulable imaging
      plates versus conventional angiography.
AB  - PURPOSE: To compare nonstepping digital subtraction angiography (DSA) (ie,
      storage phosphor radiography adapted to a stationary imaging plate changer) with
      conventional screen-film angiography in the evaluation of the lower extremities.
      MATERIALS AND METHODS: Fifty-one patients with peripheral vascular disease
      underwent both nonstepping DSA and screen-film angiography. The angiographic and
      radiologic techniques of both systems were kept identical for each patient. Three
      radiologists independently rated the overall quality of each angiogram. In their
      evaluations for each of 12 arterial segments on all 102 angiograms, they also
      rated the degree of opacification, the diameter reduction of the most severe
      stenosis, and their level of confidence. RESULTS: Mean overall quality scores and
      levels of confidence were better for nonstepping DSA than for screen-film
      angiography (P < .001). Full opacification was reported in 95.6% and 89.2% of all
      1,836 segments with nonstepping DSA and screen-film angiography, respectively (P
      < .0001). The difference between the mean stenosis grades obtained with screen
      film angiography and nonstepping DSA was not statistically significant.
      Intertechnique agreements were good (kappa = 0.77, 0.81, and 0.81), whereas
      interobserver agreements were influenced by the observer's experience with the
      imaging techniques. CONCLUSION: Nonstepping DSA images of the lower extremity
      were of better diagnostic quality than were screen-film angiograms. The
      development of dedicated nonstepping DSA equipment is warranted.

PMID- 9609893
TI  - Abdominal percutaneous interventional procedures: comparison of CT and US
      guidance.
AB  - PURPOSE: To compare ultrasound (US) with computed tomography (CT) as a guidance
      modality for percutaneous interventional procedures. MATERIALS AND METHODS: A
      database of abdominal interventional procedures was reviewed for the 6 months
      preceding and 6 months after the opening of a dedicated US interventional suite.
      Changes in the number and type of procedures performed, room time, number of
      needle passes, and complication rates were calculated. RESULTS: In the first 6
      months, 305 interventional procedures (138 tissue biopsies and 167 fluid
      aspirations) were performed (CT guidance in 87% [n = 120] and 95% [n = 159],
      respectively). In the 6 months after installation of the suite, 395 procedures
      (195 tissue biopsies and 200 fluid aspirations) were performed (US guidance in
      76% [n = 148] and 34% [n = 67], respectively). The largest increase in US
      utilization was for guidance of tissue biopsies, rising from 6% (18 of 305) to
      37% (148 of 395) of all procedures. Room time was significantly less for US
      guided procedures (mean US room time, 77 minutes +/- 33 [1 standard deviation];
      mean CT room time, 99 minutes +/- 38; P < .0001). CONCLUSION: US guidance often
      allows performance of quicker, more accurate procedures than does CT guidance,
      probably because of its real-time capabilities.

PMID- 9609894
TI  - Doppler sonography of the portal vein and hepatic artery: measurement of a
      prandial effect in healthy subjects.
AB  - PURPOSE: To determine if the prandial effect outweighs variability in the
      measurement of portal venous blood flow and hepatic arterial resistive index.
      MATERIALS AND METHODS: Fourteen healthy adult volunteers fasted overnight. For
      eight of the subjects, two sonographers performed three determinations of portal
      venous blood flow and hepatic arterial resistive index before and 30 minutes
      after a liquid meal (5 mg per kilogram of body weight). In the remaining six
      volunteers, determinations were made at the same time intervals but without a
      meal. The sonographers were blinded to on-screen measurements and the subject's
      prandial status. RESULTS: For subjects examined after the meal by sonographers A
      and B, respectively, portal venous blood flow increased from 144.2 to 201.7
      mL/min and from 209.2 to 331.9 mL/min and hepatic arterial resistive index
      increased from 0.70 to 0.77 and from 0.67 to 0.78. After repeated-measures
      analysis of variance, ingestion of a meal was estimated to increase portal venous
      blood flow by 96.3 mL/min (P < .001)--a change in sonographers could affect the
      measurement by 76.7 mL/min (P < .001)--and to increase hepatic arterial resistive
      index by 0.089 (P < .001)--a change in sonographers did not affect the
      measurement (P > .1). CONCLUSION: The prandial effect on portal venous blood flow
      is only marginally greater than the interobserver variation in the measurement.
      Hepatic arterial resistive index also increases after a meal, but interobserver
      differences between sonographers are minimal; therefore, it is a more robust
      measurement.

PMID- 9609895
TI  - Perflenapent emulsion: a US contrast agent for diagnostic radiology--multicenter,
      double-blind comparison with a placebo. EchoGen Contrast Ultrasound Study Group.
AB  - PURPOSE: To evaluate perflenapent emulsion as a contrast agent for ultrasound
      (US) of the liver, kidneys, and vasculature. MATERIALS AND METHODS: A randomized,
      double-blind, placebo-controlled, multicenter trial of 151 patients was
      performed. Investigators and blinded readers compared sonograms obtained after
      intravenous administration of perflenapent emulsion (0.05 mL/kg) and of a placebo
      with baseline sonograms. RESULTS: Contrast enhancement occurred in 140 of 149
      patients (94%) after perflenapent administration and in 12 patients (8%) after
      placebo administration (P < .001). Enhancement lasted 5.0-15.4 minutes with
      perflenapent and 0.1-1.7 minutes with the placebo (P < .001). Perflenapent
      enhanced or facilitated visualization of blood flow, abnormal structures, masses,
      and lesions in 138 of 147 patients (94%) versus 12 of 147 (8%) for the placebo (P
      < .001). Improved visualization assisted in the diagnosis in 105 of 143
      perflenapent studies (73%) compared with five of 143 placebo studies (3%) (P <
      .001). Diagnostic information affected case management in 71 of 148 patients
      (48%) after perflenapent administration and in nine of 148 patients (6%) after
      placebo administration (P < .001). Adverse effects associated with perflenapent
      were few and mostly mild, occurred within 30 minutes, and resolved without
      treatment. CONCLUSION: Perflenapent emulsion is a safe and effective contrast
      agent for US of the liver, kidneys, and vasculature.

PMID- 9609896
TI  - Portal vein anomaly associated with deviation of the ligamentum teres to the
      right and malposition of the gallbladder.
AB  - PURPOSE: To develop a complete clinical picture of a portal vein anomaly
      associated with a rightward-deviated ligamentum teres. MATERIALS AND METHODS:
      Three hundred twenty-seven consecutive living donor candidates for partial liver
      transplantation were evaluated for hepatic vascular abnormalities with computed
      tomography supplemented with intraoperative examinations. Special attention was
      given to the branching pattern of the portal system and the relative positions of
      the umbilical portion of the portal vein, the ligamentum teres, and the
      gallbladder. RESULTS: Four donor candidates (1.2%) had a portal vein anomaly
      associated with a rightward-deviated ligamentum teres. In all four, the umbilical
      portion of the portal vein (and hence the ligamentum teres) was abnormal, lying
      above the gallbladder bed and giving off major branches to the right anterior
      segment. If unrecognized, these might have been ligated, leading to major
      complications in the donors. CONCLUSION: A portal vein anomaly associated with a
      rightward-deviated ligamentum teres is an important clinical entity that is not
      as rare as indicated in the literature. This anomaly should be kept in mind
      during preoperative examination of the liver.

PMID- 9609897
TI  - Progressive viral-induced cirrhosis: serial MR imaging findings and clinical
      correlation.
AB  - PURPOSE: To determine which magnetic resonance (MR) imaging findings of cirrhosis
      change as disease severity progresses. MATERIALS AND METHODS: Seventy-six
      abdominal MR imaging studies in 38 patients (two per patient) with Child-Pugh
      grade A cirrhosis were retrospectively reviewed. All patients were followed up
      clinically and with MR imaging for 12 months or longer. MR images were used to
      determine volume indexes of the spleen and of each liver segment, as well as
      changes in hepatic contour, iron or fat deposition, and presence of varices and
      collateral vessels. RESULTS: During follow-up in patients with progressive
      cirrhosis (n = 13), the volume indexes of the anterior, posterior, and medial
      segments of the liver decreased significantly (P = .011, .013, .002,
      respectively), and the number of varices and collateral vessels increased
      significantly (P = .018). In patients with stable cirrhosis (n = 25), the volume
      indexes of the spleen, caudate lobe, and lateral segment increased significantly
      (P = .032, .018, .003, respectively). The atrophic index was significantly
      greater in progressive cirrhosis than in stable cirrhosis (P = .009). CONCLUSION:
      Progressive atrophy of the right hepatic lobe and the medial segment correlated
      with progression of clinical severity of cirrhosis, whereas increasing size of
      the caudate lobe and the lateral segment correlated with stability.

PMID- 9609898
TI  - Biliary stricture caused by blunt abdominal trauma: clinical and radiologic
      features in five patients.
AB  - PURPOSE: To evaluate the clinical and radiologic features of biliary stricture
      after blunt abdominal trauma and to report the results of endoscopic stent
      placement. MATERIALS AND METHODS: Medical records and radiologic findings were
      reviewed in five patients with biliary stricture after blunt abdominal trauma.
      The level, length, and contour of the strictures were analyzed with endoscopic
      retrograde cholangiopancreatography (ERCP). Computed tomographic (CT) scans were
      also reviewed to determine the presence of biliary dilatation, configuration of
      the injured bile duct, and ancillary abdominal findings. Results from endoscopic
      stent placement were evaluated in all patients. RESULTS: Stricture occurred in
      the suprapancreatic portion of the common bile duct in four patients and in the
      intrapancreatic portion in one patient. At ERCP, the stricture contour was
      concentric and smooth in three patients, eccentric and smooth in one, and
      abruptly terminated in one. CT showed abrupt narrowing of the common bile duct
      with dilatation of the proximal portion in all patients. Endoscopic stent
      placement was successful in all patients. CONCLUSION: Patients with biliary
      stricture after blunt abdominal trauma exhibit a delayed onset of symptoms. A
      correct diagnosis may be difficult on the basis of findings from CT or ERCP alone
      without a clinical history or evidence of contusions at other sites.

PMID- 9609899
TI  - Right ventricular arrhythmia in the absence of arrhythmogenic dysplasia: MR
      imaging of myocardial abnormalities.
AB  - PURPOSE: To evaluate right ventricular abnormalities with magnetic resonance (MR)
      imaging in patients with arrhythmia but without arrhythmogenic dysplasia.
      MATERIALS AND METHODS: In 53 patients being evaluated for right ventricular
      arrhythmia and 15 control subjects, MR imaging was performed to evaluate fixed
      thinning, fatty replacement, or reduced systolic wall thickening or motion. A
      diagnosis of idiopathic right ventricular outflow tract tachycardia or
      indeterminate was assigned for each patient, and the severity of arrhythmia was
      categorized. RESULTS: Right ventricular abnormalities were revealed in 32 (60%)
      of the 53 patients: fixed thinning in 27 (84%), fatty replacement in eight (25%),
      and reduced wall thickening or motion in 31 (97%). Right ventricular
      abnormalities were found in 35 (76%) of 46 patients with idiopathic right
      ventricular outflow tract tachycardia and in seven (39%) of 18 patients with
      indeterminate diagnoses (P = .022). CONCLUSION: Mild right ventricular
      abnormalities are likely sources for arrhythmias, even in the absence of
      arrhythmogenic right ventricular dysplasia.

PMID- 9609900
TI  - Acute pulmonary embolism: ancillary findings at spiral CT.
AB  - PURPOSE: To determine the value of parenchymal findings at contrast material
      enhanced spiral computed tomography (CT) in patients suspected to have pulmonary
      embolism (PE). MATERIALS AND METHODS: Eighty-eight patients suspected to have PE
      underwent contrast-enhanced spiral CT and ventilation-perfusion scintigraphy.
      Concordance between CT and scintigraphic results was used to diagnose or exclude
      PE. Pulmonary angiography was attempted in all patients with discordant CT and
      scintigraphic results or indeterminate scans. Parenchymal CT scans were assessed
      by two radiologists who were not aware of the diagnosis and who had access only
      to lung window images. RESULTS: Twenty-six patients had PE; 62 did not. Wedge
      shaped pleural-based consolidation was seen in 16 patients with PE (62%) and 17
      patients without PE (27%) (P < .05) (sensitivity, 62%; specificity, 73%). Linear
      bands were seen in 12 patients with PE (46%) and 13 patients without PE (21%) (P
      < .05) (sensitivity, 46%; specificity, 79%). There was no statistically
      significant difference in the frequency of non-wedge-shaped consolidation, areas
      of decreased attenuation, or atelectasis. Central and lower-lobe segmental
      pulmonary arteries that contained emboli were enlarged (P < .05). CONCLUSION:
      Parenchymal findings may suggest further investigations when results of spiral CT
      are inconclusive in diagnosis of PE.

PMID- 9609901
TI  - Intrapulmonary lesions: percutaneous automated biopsy with a detachable, 18
      gauge, coaxial cutting needle.
AB  - PURPOSE: To evaluate a lung biopsy technique in which a detachable, 18-gauge,
      coaxial guide around a central notched stylet is used as a cutting needle.
      MATERIALS AND METHODS: The records of 89 consecutive patients (41 women, 48 men;
      aged 21-86 years) who underwent coaxial percutaneous core biopsy of 91 lung
      lesions that required needle passage through normal lung tissue (mean lesion
      size, 33.6 mm; range, 9-80 mm) were studied. Detachable, 18-gauge, coaxial
      automated cutting needles were used. RESULTS: The mean number of needle passes
      was 2.5 (range, 1-4). All biopsies yielded sufficient tissue for histopathologic
      (n = 91) and, if necessary, bacteriologic (n = 12) evaluation (mean core length,
      5 mm; range, 1-15 mm). Eighty-nine lesions had definitive diagnoses. Seventy-five
      lesions were proved to be malignant; seventy (93%) could be accurately diagnosed
      with coaxial percutaneous core biopsy samples. Fourteen lesions were proved to be
      benign; 10 (71%) were specifically diagnosed with biopsy samples. Among the 91
      biopsies, the overall diagnostic accuracy was 88% (80 of 91 lesions). A
      pneumothorax occurred in 31 cases (34%), three (3%) of which necessitated
      placement of a chest tube. Postbiopsy hemoptysis occurred and resolved
      spontaneously in nine cases (10%). CONCLUSION: This technique provides a core
      biopsy specimen without the need for an on-site cytopathologist during the
      procedure. It has a high diagnostic accuracy and an acceptable rate of
      complications.

PMID- 9609902
TI  - Untreated primary lung and breast cancers: correlation between F-18 FDG kinetic
      rate constants and findings of in vitro studies.
AB  - PURPOSE: To compare kinetic modeling of 2-[fluorine-18]fluoro-2-deoxy-D-glucose
      (F-18 FDG) between untreated primary lung and untreated primary breast cancers by
      using positron emission tomographic (PET) findings and to correlate these
      findings with findings of in vitro studies. MATERIALS AND METHODS: Nineteen
      patients (12 men, seven women; age range, 49-82 years) with untreated primary
      lung cancer and 17 women with untreated primary breast cancer (age range, 26-65
      years) underwent 1-hour dynamic F-18 FDG PET. A three-compartment model was
      applied to F-18 FDG kinetics in tumors. The standard uptake value normalized for
      lean body mass (SUVlean) in tumors was measured 50-60 minutes after tracer
      injection. In vitro, thin-layer chromatography was performed to evaluate the
      intracellular phosphorylation of tritiated F-18 FDG in human lung cancer and
      breast cancer cell lines. RESULTS: At PET, lung cancer had a significantly (P <
      .003) higher rate constant for F-18 FDG phosphorylation (k3) and SUVlean than did
      breast cancer (0.164 +/- 0.150 [standard deviation] vs 0.043 +/- 0.018 and 8.25
      +/- 3.28 vs 3.17 +/- 1.08, respectively). Breast cancer showed a significant
      correlation between k3 and SUVlean (r = .607, P < .01), although no such
      correlation was observed in lung cancer. In vitro studies showed phosphorylation
      of F-18 FDG in breast cancer cells was less complete in hyperglycemia than it was
      in lung cancer cells. CONCLUSION: A much lower k3 appears to be a rate-limiting
      factor for F-18 FDG accumulation in breast cancer, while the higher k3 in lung
      cancer is probably not rate limiting for F-18 FDG accumulation.

PMID- 9609903
TI  - Chronic thyroiditis: diffuse uptake of FDG at PET.
AB  - PURPOSE: To determine the frequency and clinical importance of diffuse 2
      [fluorine-18]fluoro-2-deoxy-D-glucose (FDG) uptake in the thyroid gland.
      MATERIALS AND METHODS: A total of 1,102 healthy subjects underwent whole-body
      positron emission tomography (PET). PET images were evaluated for increased
      diffuse FDG uptake in the thyroid gland. Serum free thyroxine and thyrotropin
      levels were measured in 36 subjects with increased uptake and in 36 matched
      control subjects without uptake. Antithyroid antibodies were also measured.
      Morphologic abnormalities were examined by using ultrasonography (US). RESULTS:
      Diffuse FDG uptake was found in three men and 33 women; the prevalence was
      significantly higher in women (P < .01). Thirty-five subjects were euthyroid; one
      had hypothyroidism. Antithyroid antibodies were positive in 27 subjects. In most
      subjects, US findings facilitated the diagnosis of chronic thyroiditis. In
      control subjects, the positive rates for antithyroid antibodies and US
      abnormalities were significantly lower than those of the study group (P < .01).
      CONCLUSION: Diffuse thyroidal FDG uptake may be an indicator of chronic
      thyroiditis. The actual prevalence of the disorder was not low in this series,
      and such lesions may be found incidentally at FDG PET.

PMID- 9609904
TI  - Lung cancer: intermittent irradiation synchronized with respiratory motion-
      results of a pilot study.
AB  - PURPOSE: To test the feasibility of a system for intermittent irradiation
      synchronized with respiratory motion in a clinical setting. MATERIALS AND
      METHODS: A newly developed gate pulse controller that starts and stops
      irradiation at a chosen phase of the respiratory cycle by controlling a linear
      accelerator was used in six patients with lung cancer. A laser displacement
      sensor was used for the detection of respiratory motion. Three patients underwent
      radiation therapy during the cycles between 50% expiration and 50% inspiration
      (step 1), and three patients underwent radiation therapy during the cycles
      between 70% expiration and 30% inspiration (step 2). RESULTS: The system
      functioned well; irradiation was verified with portal verification radiography in
      all six patients. The range of the tumor position during synchronized irradiation
      was detectable with fast portal localization radiography. The treatment times for
      steps 1 and 2 were 1.38-1.71 and 2.03-2.18 times longer, respectively, than those
      for conventional irradiation. CONCLUSION: Synchronized irradiation with the
      authors' system allowed convenient and reliable reduction of the target volume.
      Further study is needed to standardize the system for clinical use.

PMID- 9609905
TI  - Intraobserver and interobserver variability of MR imaging- and CT-derived
      prostate volumes after transperineal interstitial permanent prostate
      brachytherapy.
AB  - PURPOSE: To evaluate the relative accuracy and precision of magnetic resonance
      (MR) imaging and computed tomography (CT) in the assessment of postimplantation
      prostate volume by determining intraobserver, interobserver, and intermodality
      variations. MATERIALS AND METHODS: CT and MR images of 41 consecutive patients,
      after transperineal interstitial permanent prostate brachytherapy, were evaluated
      by two physicians to determine interobserver and intermodality variability in
      prostate volume measurements. Repeat evaluation in five randomly selected
      patients was used to determine intraobserver variability. RESULTS: Observer 1
      versus 2 CT-determined mean prostate volume difference was statistically
      significant (-8.5 cm3 +/- 9.74 [standard deviation], P < .001); observer 1 versus
      2 MR-determined mean prostate volume difference was not significant (1.9 cm3 +/-
      11.7, P = .492). CT intraobserver range of dimensional errors was 3.5 and 11.4
      times that of MR imaging. Observer 1 CT and MR volumes were significantly
      different (P = .001); observer 2 CT and MR volumes were not significantly
      different (P = .079). CONCLUSION: With both CT and MR imaging, variation is less
      when evaluations are conducted by one observer. Variation in one observer may be
      further reduced by using MR imaging in place of CT.

PMID- 9609906
TI  - Evaluation of chemotherapy in advanced urinary bladder cancer with fast dynamic
      contrast-enhanced MR imaging.
AB  - PURPOSE: To evaluate if the failure of chemotherapy in patients with advanced
      urinary bladder cancer can be predicted early in the course of chemotherapy with
      fast dynamic contrast material-enhanced magnetic resonance (MR) imaging.
      MATERIALS AND METHODS: In this prospective study, 22 consecutive patients with
      histologically proved advanced urinary bladder cancer underwent MR imaging before
      and after two, four, and six cycles of chemotherapy with methotrexate,
      vinblastine, adriamycin, and cisplatin (MVAC). The response after two
      chemotherapy cycles was evaluated by using conventional tumor size parameters at
      unenhanced MR imaging and with changes in the time to the start of tumor or lymph
      node enhancement at fast dynamic contrast-enhanced MR imaging. The results
      obtained with these techniques were compared with the findings at histopathology
      in cystectomy (n = 9) or multiple transurethral resection (n = 13) specimens
      obtained after completion of chemotherapy. RESULTS: After two MVAC cycles, the
      accuracy, sensitivity, and specificity in distinguishing responders from
      nonresponders with conventional MR imaging were 73%, 79%, and 63%, respectively.
      With the dynamic technique, these were 95%, 93%, and 100%, respectively. Although
      the differences between these values are not significant (P = .48 for
      sensitivity, .25 for specificity, and .07 for accuracy), the data indicate that
      dynamic enhanced MR imaging performed better than unenhanced MR imaging. Dynamic
      imaging yielded correct results after two MVAC cycles in 21 cases, and in all
      cases after four cycles. After four MVAC cycles, the accuracy of dynamic MR
      imaging was significantly better (P < .05). Persisting early enhancement after
      four MVAC cycles correctly corresponded with lack of response in all nine cases,
      and after two cycles in eight of these cases. The unenhanced MR technique showed
      initial tumor size reduction in three of these cases. CONCLUSION: Conventional
      and dynamic enhanced MR imaging were used to evaluate chemotherapy after two,
      four, and six cycles of MVAC in 22 patients with bladder cancer. After two
      cycles, dynamic MR imaging helped detect 13 of 14 responders and eight of eight
      nonresponders. It helped detect five of seven lymph node responders and two of
      two nonresponders. Thus, it may be possible to predict after two MVAC cycles
      whether a patient will respond to chemotherapy.

PMID- 9609907
TI  - Lymph node metastases: safety and effectiveness of MR imaging with ultrasmall
      superparamagnetic iron oxide particles--initial clinical experience.
AB  - PURPOSE: To evaluate the clinical and biologic safety of ultrasmall
      superparamagnetic iron oxide particles (AMI-227) as a contrast agent for magnetic
      resonance (MR) lymphography and to assess their efficacy for the differentiation
      of metastatic and benign nodes in patients with urologic and pelvic cancer.
      MATERIALS AND METHODS: Thirty adults suspected of having lymph node metastases
      underwent MR imaging before and 22-26 hours after intravenous infusion of AMI-227
      (1.7 mg Fe/kg). Sixty histopathologically proved lymph nodes were analyzed on MR
      images, and 29 of these nodes were also analyzed quantitatively. RESULTS: AMI-227
      was well tolerated with no major side effects. It allowed the detection of 10
      additional nodes relative to those detected at MR imaging without AMI-227. None
      of the 27 metastatic nodes showed a decrease in signal intensity (SI) on AMI-227
      enhanced images; nine of 27 metastatic nodes showed an increase in SI on T1
      weighted images, probably resulting from altered capillary permeability in the
      tumor. A visually perceptible reduction in SI, indicating active AMI-227 uptake,
      was observed on postcontrast T2- and T2*-weighted images in 16 of 21 benign
      nodes. The SI ratio of benign nodes was lower than that of metastatic nodes on T2
      and T2*-weighted images. The sensitivity of AMI-227-enhanced MR lymphography was
      100%, and the specificity was 80%. CONCLUSION: AMI-227 is safe and may facilitate
      the differentiation of metastatic and benign nodes in patients with urologic and
      pelvic cancers.

PMID- 9609908
TI  - Selective salpingography and fallopian tubal occlusion with n-butyl-2
      cyanoacrylate: report of two cases.
AB  - Selective salpingography with fluoroscopic guidance was used to perform fallopian
      tubal occlusion by using n-butyl-2-cyanoacrylate in two women. No other method of
      sterilization was possible, and a new pregnancy was considered to be life
      threatening. After 4 years of follow-up, neither woman had become pregnant. Tubal
      occlusion with n-butyl-2-cyanoacrylate is a safe, effective and inexpensive means
      of sterilization that provides long-term occlusion.

PMID- 9609910
TI  - Cervical spine: three-dimensional MR imaging with magnetization transfer
      prepulsed turbo field echo techniques.
AB  - In 11 volunteers, magnetic resonance (MR) imaging of the cervical spine was
      performed with a magnetization transfer preparatory pulse (prepulsed), three
      dimensional Fourier transform, turbo field echo sequence. The effects of flip
      angle, number of shots, phase-encoding profile order, and magnetization transfer
      prepulse offset frequency on cerebrospinal fluid-to-cord contrast were evaluated.
      The contrast was improved by lowering the flip angle, increasing the number of
      shots, and implementing a magnetization transfer prepulse and linear phase
      encoding profile order. Maximum myelographic effect was achieved with the
      magnetization prepulse (500-Hz frequency offset), 3 degrees flip angle, six
      shots, and linear phase-encoding profile order.

PMID- 9609911
TI  - Cranial bone flap fixation clamps: compatibility at MR imaging.
AB  - Metallic cranial bone flap fixation clamps were tested for compatibility at 1.5-T
      magnetic resonance (MR) imaging with standardized techniques. There was no
      magnetic field attraction, heating was minor, and artifacts involved a relatively
      small signal void. These data indicate that bone flap fixation clamps will not
      present risks to patients undergoing MR imaging procedures with MR systems of 1.5
      T or less.

PMID- 9609912
TI  - Shin splints.

PMID- 9609913
TI  - Selective use of low-osmolality contrast media in biphasic helical CT of the
      liver.

PMID- 9609914
TI  - Cigarette smoke-induced acute eosinophilic pneumonia.

PMID- 9609915
TI  - Hepatic enhancement at dual-phase helical CT.

PMID- 9609916
TI  - Miss rates for surgical biopsy of needle-localized breast lesions.

PMID- 9609917
TI  - Contrast medium dose and renal failure.

PMID- 9609918
TI  - The use of ACE inhibitors for congestive heart failure among Delaware Medicare
      beneficiaries.
AB  - The analysis upon which this publication is based was performed under Contract
      Number 500-96-P603, entitled, Utilization and Quality Control Peer Review
      Organization for the State of Delaware, as sponsored by the Health Care Financing
      Administration (HCFA), Department of Health and Human Services. The content of
      this publication does not necessarily reflect the views or policies of the
      Department of Health and Human Services, nor does mention of trade names,
      commercial products, or organizations imply endorsement by the U.S. Government.
      The author assumes full responsibility for the accuracy and completeness of the
      Health Care Quality Improvement Program initiated by HCFA, which has encouraged
      identification of quality improvement projects derived from analysis of patterns
      of care, and therefore, required no special funding on the part of this
      Contractor. Ideas and contributions to the author concerning experience in
      engaging with issues presented are welcomed.

PMID- 9609919
TI  - Useful sites on the Internet.
AB  - Internet medical sites offer the physician opportunities to improve patient care,
      to obtain continuing education and medical management services, and the ability
      to communicate with colleagues. This paper discusses how to choose the best
      sites, and highlights some valuable federal, university and commercial medical
      sites found on the Internet.

PMID- 9609920
TI  - ACE inhibitor use for CHF in Delaware.

PMID- 9609921
TI  - [Pneumonia in ambulatory care patients. Choice of antibiotics for therapy of
      community-acquired pneumonia].
AB  - According to the statistics prepared by health insurance carriers community
      acquired pneumonia has an incidence of some 300,000 to 400,000 cases per year. In
      old age (more than 80 years), the mortality rate increases from 20 to 2000 per
      100,000 head of the population, that is, by a factor of 100. The former
      classification into "typical" and "untypical" pneumonia has now been abandoned,
      the modern approach being that of "calculated antibiotic therapy" that involves
      the placing of patients in "risk groups". To each risk group a probable pathogen
      spectrum is assigned and a recommendation for the selection of an appropriate
      antibiotic then made. Thus, for example, for the pathogen spectrum in group 1
      (ambulatory patients under 60 years of age and no major secondary diseases), the
      macrolides are the antibiotics of first choice. The procedure to be followed in
      the other risk groups and in the event of treatment failures is discussed.
      Criteria that identify the need for hospitalization are presented.

PMID- 9609922
TI  - [Diagnostic procedure in renal artery stenosis].

PMID- 9609923
TI  - [New developments in neuroradiologic diagnosis. Indications for MRI and PET-
      advances in functional imaging].
AB  - In the field of neuroradiology in particular, a number of special indications
      have been identified for which the new generation of imaging procedures, MRT and
      PET are superior to other technologies currently available. This applies, for
      example, to MRT used to investigate MS, herpes encephalitis, certain forms of
      epilepsy and arteriovenous anomalies or cavernomas. Further developments of the
      MRT technique are being used to visualize vascular anomalies or the penumbra in
      the case of cerebral infarction. Here, MRT is increasingly entering the area of
      functional imaging which, however, is primarily the domain of PET. For the first
      time, PET now allows us to objectify such otherwise merely subjective symptoms as
      chronic pain or tinnitus. In the preoperative diagnosis of epilepsy, for example
      in the case of temporal lobe epilepsy, PET has now been accepted as the standard
      technique.

PMID- 9609924
TI  - [Diagnostic imaging in rheumatology. I: Typical roentgen signs (conventional)].

PMID- 9609925
TI  - [Letter from the President of the Austrian Society of Gynecology and Obstetrics].

PMID- 9609926
TI  - [Epidemiology and diagnosis of cervical intraepithelial neoplasia--is the present
      concept of screening and diagnosis still current?].
AB  - Infection with human papillomavirus (HPV) is the major factor in the genesis of
      cervical intraepithelial (CIN) and invasive neoplasia. However, screening is
      still based upon cytology and further diagnostic investigation relies on
      colposcopy with punch biopsy. In this review, recent studies are evaluated with
      regard to consequences for optimal screening and management strategies of CIN. In
      summary, exfoliative cytology is still widely considered as the method of choice
      for population screening. Primary HPV DNA screening proves equivalent or superior
      to cytology only in populations with a low prevalence of HPV infections.
      Preliminary data from serological HPV tests are less promising. Cytological
      diagnosis of HPV infection may be verified by HPV testing. Recognizing high
      oncogenic risk viruses in CIN 1 may help to reduce the control period from 24 to
      12 months and may lead to immediate therapy for CIN 2 lesions. However, further
      prospective studies evaluating the cost-effectiveness of HPV DNA tests in German
      speaking countries are necessary.

PMID- 9609928
TI  - [Fetal outcome in reduced flow in the ductus venosus during atrial contraction].
AB  - OBJECTIVE: To document the fetal outcome in cases with pathologic Doppler
      findings in the fetal ductus venosus. METHODS: The outcome of 12 fetuses with
      reduced velocities in the ductus venosus during atrial contraction was analyzed
      retrospectively and compared with that of a group of 57 fetuses with normal flow
      velocities in the umbilical artery and in the fetal ductus venosus. RESULTS: The
      perinatal mortality was higher in the group with pathologic Doppler findings.
      There was no significant difference of pH (7.20 vs. 7.24) and Apgar scores (7.57
      vs. 8.36) of survivors between the two groups. All 12 fetuses showed increased
      retrograde velocities in the inferior vena cava. Seven fetuses showed umbilical
      vein pulsations. CONCLUSIONS: The diagnosis of altered velocities in the ductus
      venosus may influence prenatal decisions. Therefore Doppler examinations of the
      fetal ductus venosus should be performed in high-risk pregnancies.

PMID- 9609927
TI  - [Fetal blood analysis--pro and contra].
AB  - OBJECTIVE: Fetal blood gas analysis (FBA) or micro blood gas analysis (MBU) is
      seen worldwide as an integral part of modern obstetrics. However, there are a
      number of obstetricians who practise obstetrics quite safely and competently
      without MBU. The aim of this study was to find out what effect MBU frequency (%)
      had on vital obstetric performance parameters. METHODS: This study was based on
      the obstetric parameters of 1,003 clinics in Ostwestfalen-Lippe in the years 1990
      1996. The percentages of 10 principal variables (including cesarean section,
      forceps, acidosis rates, postpartal mortality) were calculated per clinic/year.
      Correlations (according to Kendall) were established between the individual
      variables to estimate the influence of MBU frequency (%) on the different
      variables. Data from the 1,003 clinics in the years 1990-1996 could be pooled.
      RESULTS: Approximately 91% of all clinics perform FBA. The mean MBU frequency is
      6.1 +/- 10.1%, the median is 2.3%. Upward variance is large: the 90th percentile
      of MBU distribution amounts to 15.5, the 95th centile to 22.6%. There is no
      correlation between MBU frequency (%) and clinic size, measured by the number of
      children born per year. There is no statistically relevant connection between the
      acidosis rate (%) in umbilical artery (UA) blood and MBU frequency. The same
      holds true for mortality (%) of neonates in the first week. However, there is a
      highly significant positive correlation between MBU frequency on the one hand and
      cesarean and forceps rates (%) on the other. Clinics without FBA (n = 88,
      approximately 9%) have obstetric performance figures that are as good as those of
      the total amount of clinics examined. There is no correlation between the
      acidosis rate (pH < 7.100, UA (%)) and neonatal mortality in the first week.
      However, a significant correlation between pH values < 7.000 (UA) and an
      increased postnatal mortality (p < 0.001) has been observed. CONCLUSIONS: In
      analogy to cardiotocography, cesarean and forceps rates are increased in FBA,
      although there is no statistically significant decrease in acidosis morbidity and
      postpartal mortality. These figures support the observation that obstetrics
      without FBA is possible and legitimate. The significance of FBA for fetal
      diagnosis lies in the small number of cases where cardiotocograms are hard to
      interpret. Therefore, every obstetrician should be able to handle it. A new
      evaluation of pH values is discussed.

PMID- 9609929
TI  - [Cervical pregnancy. A gynecologic-obstetric emergency situation].
AB  - The cervical pregnancy is defined as the implantation of the blastocyst into the
      cervical canal. The characteristic clinical sign is a severe asymptomatic uterine
      bleeding in early pregnancy or during curettage. Prior to 1978, correct
      preoperative diagnosis was rare and in almost all cases a hysterectomy was
      performed. Today, transvaginal sonography allows early diagnosis, and
      conservative treatment (two-time treatment: first treatment with systemic or
      intraamniotic methotrexate, secondly with curettage or ligature of the uterine
      arteries) improves the prospects of fertility.

PMID- 9609930
TI  - [Primary fallopian tube carcinoma. Report of a single case with review of the
      literature].
AB  - With an incidence of 0.1-1.0% of all genital malignancies, primary fallopian tube
      carcinoma is an extremely uncommon neoplasm of the female genital tract. We
      report a 58-year-old postmenopausal woman with primary fallopian tube carcinoma
      confined to the right fallopian tube in primary stage pT2a pN0 G3 M0, who is
      alive without evidence of disease 2 years after abdominal hysterectomy, bilateral
      adnexectomy, omentectomy and lymphonodectomy followed by an adjuvant cisplatin
      (70 mg/m2) and treosulfan (5 g/m2) chemotherapy. An accompanying literature
      review indicates that clinical signs and symptoms of fallopian tube neoplasms are
      usually nonspecific and include lower abdominal pain. The primary treatment
      remains surgical resection followed by adjuvant chemotherapy or radiation.
      Prognosis is poor, although long-term survivors have been reported.

PMID- 9609931
TI  - [Survival prognosis in ovarian carcinoma Figo stages III and IV: 1980-1985 versus
      1986-1993. A comparison of 2 treatment periods].
AB  - We examined the survival prognosis of 638 patients who had ovarian carcinoma Figo
      stages III and IV. We considered two separate time periods, 1980-1985 versus 1986
      1993, including the size of the postoperative residual tumor, polychemotherapy
      with and without platinum, histological grading 1 versus 2 and 3, Figo stage III
      versus IV, and ascites present versus no ascites. Since 1986, 96% of the patients
      received platinum-containing polychemotherapy at a dosage of > or = 75 mg/m2,
      whereas between 1980 and 1985, only 76% of these patients received platinum
      containing polychemotherapy at a dosage of 50 mg/m2, and 24% of the patients
      received polychemotherapy without platinum. The size of residual tumor masses and
      also the time period of treatment had an independent influence on survival
      prognosis. Patients treated from 1980 to 1985 had a relative risk to die which
      was 1.44 times higher than for the patients who were studied from 1986 to 1993.

PMID- 9609932
TI  - [Guidelines for surgical treatment of cervix carcinoma developed by the Standard
      Committee of the Austrian Society of Gynecology and Obstetrics. Austrian Society
      of Gynecology and Obstetrics].

PMID- 9609933
TI  - Seizure detection of newborn EEG using a model-based approach.
AB  - Seizures are often the first sign of neurological disease or dysfunction in the
      newborn. However, their clinical manifestation is often subtle, which tends to
      hinder their diagnosis at the earliest possible time. This represents an
      undesirable situation since the failure to quickly and accurately diagnose
      seizure can lead to longer-term brain injury or even death. In this paper we
      consider the problem of automatic seizure detection in the neonate based on
      electroencephalogram (EEG) data. We propose a new approach based on a model for
      the generation of the EEG, which is derived from the histology and biophysics of
      a localized portion of the brain. We show that by using this approach, good
      detection performance of electrographic seizure is possible. The model for
      seizure is first presented along with an estimator for the model parameters. Then
      we present a seizure-detection scheme based on the model parameter estimates.
      This scheme is compared with the quadratic detection filter (QDF), and is shown
      to give superior performance over the latter. This is due to the ability of the
      model-based detector to account for the variability (nonstationarity) of the EEG
      by adjusting its parameters appropriately.

PMID- 9609934
TI  - Wavelet analysis of click-evoked otoacoustic emissions.
AB  - Time-frequency distribution methods are being widely used for the analysis of a
      variety of biomedical signals. Recently, they have been applied also to study
      otoacoustic emissions (OAE's), the active acoustic response of the hearing end
      organ. Click-evoked otoacoustic emissions (CEOAE's) are time-varying signals with
      a clear frequency dispersion along with the time axis. Analysis of CEOAE's is of
      considerable interest due to their close relation with cochlear mechanisms. In
      this paper, several basic time-frequency distribution methods are considered and
      compared on the basis of both simulated signals and real CEOAE's. The particular
      structure of CEOAE's requires a method with both a satisfactory time and
      frequency resolution. Results from simulations and real CEOAE's revealed that the
      wavelet approach is highly suitable for the analysis of such signals. Some
      examples of the application of the wavelet transform to CEOAE's are provided
      here. Applications range from the extraction of normative data from adult and
      neonatal OAE's to the extraction of quantitative parameters for clinical
      purposes.

PMID- 9609935
TI  - Power spectral density of unevenly sampled data by least-square analysis:
      performance and application to heart rate signals.
AB  - This work studies the frequency behavior of a least-square method to estimate the
      power spectral density of unevenly sampled signals. When the uneven sampling can
      be modeled as uniform sampling plus a stationary random deviation, this spectrum
      results in a periodic repetition of the original continuous time spectrum at the
      mean Nyquist frequency, with a low-pass effect affecting upper frequency bands
      that depends on the sampling dispersion. If the dispersion is small compared with
      the mean sampling period, the estimation at the base band is unbiased with
      practically no dispersion. When uneven sampling is modeled by a deterministic
      sinusoidal variation respect to the uniform sampling the obtained results are in
      agreement with those obtained for small random deviation. This approximation is
      usually well satisfied in signals like heart rate (HR) series. The theoretically
      predicted performance has been tested and corroborated with simulated and real HR
      signals. The Lomb method has been compared with the classical power spectral
      density (PSD) estimators that include resampling to get uniform sampling. We have
      found that the Lomb method avoids the major problem of classical methods: the low
      pass effect of the resampling. Also only frequencies up to the mean Nyquist
      frequency should be considered (lower than 0.5 Hz if the HR is lower than 60
      bpm). We conclude that for PSD estimation of unevenly sampled signals the Lomb
      method is more suitable than fast Fourier transform or autoregressive estimate
      with linear or cubic interpolation. In extreme situations (low-HR or high
      frequency components) the Lomb estimate still introduces high-frequency
      contamination that suggest further studies of superior performance interpolators.
      In the case of HR signals we have also marked the convenience of selecting a
      stationary heart rate period to carry out a heart rate variability analysis.

PMID- 9609936
TI  - Global optimization in the localization of neuromagnetic sources.
AB  - The locations of active brain areas can be estimated from the magnetic field
      produced by the neural current sources. In many cases, the actual current
      distribution can be modeled with a set of stationary current dipoles with time
      varying amplitudes. This work studies global optimization methods that find the
      minimum of the least-squares error function of the current dipole estimation
      problem. Three different global optimization methods were investigated:
      clustering method, simulated annealing, and genetic algorithms. In simulation
      studies, the genetic algorithm was the most effective method. The methods were
      also applied to analysis of actual measurement data.

PMID- 9609937
TI  - A computer simulation study of cortical imaging from scalp potentials.
AB  - In this paper, computer simulation studies were conducted to test the feasibility
      of imaging brain electrical activity from the scalp electroencephalograms. The
      inhomogeneous three-concentric-sphere head model was used to represent the head
      volume conductor. Closed spherical dipole layers, consisting of several thousand
      uniformly distributed dipoles, were used to reconstruct the cortical potential
      maps corresponding to neuronal sources located inside the brain. Simulation
      results indicate that the present procedure can image both cortical and deep
      sources, and for the cortical sources, a spatial resolution as high as 1.2 cm can
      be achieved.

PMID- 9609938
TI  - On the realization of an analytic high-resolution EEG.
AB  - The analytic solution of the harmonic downward continuation of the scalp
      potential field in an N-shell heterogeneous, but isotropic, spherical volume
      conductor model has been derived. The objective of this paper was to investigate
      the realization of a so-called "high-resolution electroencephalogram (EEG)": by
      enhancing the poor spatial resolution of EEG recordings. To this end, the forward
      problem for a dipolar source arbitrarily located at the source point Q = Q(rs,
      phi s, theta s) has been determined in a compact matrix notation. It is possible
      to transfer the potential field given on the outer surface of a spherically
      shaped volume conductor to an arbitrary inner surface (e.g., to the cortical
      surface) under consideration of the electrical and geometrical properties of the
      model. For the application of the proposed method to real-world problems, the
      coefficients of the series expansion describing the cortical potential
      distribution are determined by minimizing the squared curvature of the scalp
      potential field integrated over the scalp surface. Simulation results for
      distributed sources show that the proposed method is superior to the surface
      Laplacian method for interelectrode distances below 2.5 cm.

PMID- 9609939
TI  - Electric lead field for a piecewise homogeneous volume conductor model of the
      head.
AB  - A new method is presented for computing the electric lead field of a realistic
      head shape model which has piecewise homogeneous conductivity. The basic formulae
      are derived using the well-known reciprocity theorem. Previously described
      methods are also based upon this theorem, but these first calculate the electric
      potential inside the head by a scalar boundary element method (BEM), and then
      approximate the ohmic current density by some sort of gradient. In contrast, this
      paper proposes the direct evaluation of the ohmic current density by discretizing
      the vector Green's second identity which leads to a vector version of BEM. This
      approach also allows the derivation of the same equations for the three
      concentric spheres model as obtained by Rush and Driscoll [8]. The results of
      simulations on a spherical head model indicate that the use of a vector BEM leads
      to an improvement of accuracy in the computation of the ohmic current density
      with respect to those reported previously, in term of different measures of
      error.

PMID- 9609940
TI  - A mathematical model for the assessment of hemodynamic parameters using
      quantitative contrast echocardiography.
AB  - A mathematical model for the assessment of hemodynamic parameters using
      quantitative echocardiography is presented. The method involves the intravenous
      injection of an ultrasonic echo contrast agent. The relative enhancement of the
      backscattered ultrasound intensity is measured as a function of time (the time
      intensity curve). From this measurement, the volume flow rate (cardiac output)
      and the mixing volume are calculated. Relevant acoustic properties of the
      ultrasound contrast agent are discussed. An in vitro experiment is performed to
      corroborate the theory presented.

PMID- 9609941
TI  - Analysis of the electrical excitation of CNS neurons.
AB  - The artificial excitation process of neurons of the central nervous system
      depends on the applied extracellular field, on the geometry of the neuron and on
      the electrical properties of the neural subunits. Results of computer simulations
      are based on a compartment model of the neuron and its equivalent electrical
      network. Furthermore, a theory is presented which generalizes the activating
      function concept known from peripheral nerve stimulation. The theory predicts the
      influence of electrical and geometrical parameters on the excitation threshold.
      Generally, the myelinated axon is the part of a neuron which is most excitable to
      a given applied field. An example demonstrates that for a target neuron the
      quotient (anodic threshold current)/(cathodic threshold current) essentially
      depends on the position and orientation of the neuron relative to the electrode.

PMID- 9609942
TI  - A versatile system for the generation and the development of speech coding
      strategies in cochlear implants.
AB  - A signal processor-based (DSP32C) stimulation system for cochlear implants has
      been developed. This system allows up to 14 stimulation channels (place
      principle) and conserves the time structure of the acoustic signal (periodicity
      principle). Any combination of these features is possible; in compressed analogue
      mode, pulsatile mode, or combinations of both. The system also takes electrical
      crosstalk into account caused by the electrical properties of the inner ear and
      compensates for it. Lateral inhibition strategies improve spatial resolution.
      Finally, the system offers an interface for the generation of quick continuous
      interleaved sampling strategies (CIS); up to 11,000 pulses/s per channel.

PMID- 9609943
TI  - An automatic diagnostic system for CT liver image classification.
AB  - Computed tomography (CT) images have been widely used for liver disease
      diagnosis. Designing and developing computer-assisted image processing techniques
      to help doctors improve their diagnosis has received considerable interests over
      the past years. In this paper, a CT liver image diagnostic classification system
      is presented which will automatically find, extract the CT liver boundary and
      further classify liver diseases. The system comprises a detect-before-extract
      (DBE) system which automatically finds the liver boundary and a neural network
      liver classifier which uses specially designed feature descriptors to distinguish
      normal liver, two types of liver tumors, hepatoma and hemageoma. The DBE system
      applies the concept of the normalized fractional Brownian motion model to find an
      initial liver boundary and then uses a deformable contour model to precisely
      delineate the liver boundary. The neural network is included to classify liver
      tumors into hepatoma and hemageoma. It is implemented by a modified probabilistic
      neural network (PNN) [MPNN] in conjunction with feature descriptors which are
      generated by fractal feature information and the gray-level co-occurrence matrix.
      The proposed system was evaluated by 30 liver cases and shown to be efficient and
      very effective.

PMID- 9609944
TI  - Influence of smoothing window length on electromyogram amplitude estimates.
AB  - A systematic, experimental study of the influence of smoothing window length on
      the signal-to-noise ratio (SNR) of electromyogram (EMG) amplitude estimates is
      described. Surface EMG waveforms were sampled during nonfatiguing, constant
      force, constant-angle contractions of the biceps or triceps muscles, over the
      range of 10%-75% maximum voluntary contraction. EMG amplitude estimates were
      computed with eight different EMG processor schemes using smoothing length
      durations spanning 2.45-500 ms. An SNR was computed from each amplitude estimate
      (deviations about the mean value of the estimate were considered as noise). Over
      these window lengths, average +/- standard deviation SNR's ranged from 1.4 +/-
      0.28 to 16.2 +/- 5.4 for unwhitened single-channel EMG processing and from 3.2 +/
      0.7 to 37.3 +/- 14.2 for whitened, multiple-channel EMG processing (results
      pooled across contraction level). It was found that SNR increased with window
      length in a square root fashion. The shape of this relationship was consistent
      with classic theoretical predictions, however none of the processors achieved the
      absolute performance level predicted by the theory. These results are useful in
      selecting the length of the smoothing window in traditional surface EMG studies.
      In addition, this study should contribute to the development of EMG processors
      which dynamically tune the smoothing window length when the EMG amplitude is time
      varying.

PMID- 9609945
TI  - Optimal detection of visual evoked potentials.
AB  - We consider the problem of detecting visual evoked potentials (VEP's). A matched
      subspace filter is applied to the detection of the VEP and is demonstrated to
      perform better than a number of other evoked potential detectors. Unlike single
      harmonic detectors, the matched subspace filter (MSF) detector is suitable for
      detecting multiharmonic VEP's. Moreover, the MSF is optimal in the uniformly most
      powerful sense for multiharmonic signals with unknown noise variance.

PMID- 9609946
TI  - [Apoptosis: current status of the problem].
AB  - Accelerating progress in studying the nature of apoptosis (programmed cell death,
      PCD) has been observed in recent years. Apoptosis proved to be preprogrammed
      biological phenomenon with the key role in fundamental processes such as
      embryogenesis, morphogenesis, and cellular homeostasis. Apoptosis is induced by
      specific physiological signals as well as by various damaging influences. A
      complex system of metabolic and genetic control of apoptosis is realized by
      phylogenetically conserved set of genes with pro- and antiapoptotic activity.
      Genetic and metabolic disturbances of initiation and/or realization of PCD make
      substantial contribution to a number of pathologies such as cancer, AIDS, and
      degenerative processes. Active search for apoptosis-controlling remedies may open
      new horizons for fighting these widespread diseases.

PMID- 9609947
TI  - [Apoptosis and thymocyte development (epithelial cells as inducers of thymocyte
      apoptosis)].
AB  - Apoptosis, together with proliferation, is a main factor of selection of the
      clones of developing T-lymphocytes: the clones not supported by positive
      selection are subject to apoptosis and apoptosis accounts for discarding of
      potentially autoaggressive clones, i.e., for negative selection in the thymus and
      peripheral lymphoid tissue. Realization of apoptosis at different stages of the
      development of T-lymphocytes depends to a varying extent on Fas, Bcl-2, p53, and
      other regulators. The dendritic cells are the main cell type, the contact with
      determines apoptosis of T-lymphocytes. A possible role of the epithelial cells
      was shown in few models (on murine cells) and was not practically studied. We
      obtained a line of epithelial cells of the human thymus cells HTSC, cocultivation
      with which induces apoptosis of immature thymocytes and blood T-cells activated
      by mitogens. Development of apoptosis is suppressed by inhibitors of protein and
      RNA synthesis, chelators Ca2+, ions Zn2+, and factors destroying the cytoskeleton
      components. In this model, interaction of pairs of molecules CD4-HLA class II and
      LFA-1-ICAM-1. When in contact with the HTSC cells, the thymocytes of mice mutant
      for Fas-receptor (line MRL.lpr) are subject to apoptosis, but when this receptor
      is present, it affects the development of apoptosis.

PMID- 9609948
TI  - [The role of p53 gene in programmed cell death].
AB  - The gene coding for p53, a suppressor of malignant growth, is induced by various
      stress factors that cause appearance of the hereditarily pathologic cells. One of
      important p53 functions is initiation of apoptosis that eliminates potentially
      dangerous cells from the organism. The mechanism of p53-induced apoptosis are
      reviewed.

PMID- 9609949
TI  - [The role of sphingomyelin cycle products in development of apoptosis mediated by
      Fas receptors and tumor necrosis factor alpha].
AB  - Programmed cell death or apoptosis is a cell suicide developing according to a
      specific program, in which the sphingomyelin cycle products, ceramide and
      sphingosine, play the central role. The present review provides published data
      and the authors' results suggesting that the content of ceramide and sphingosine
      in the cell is controlled by the tumor necrosis factor alpha and activators of
      Fas receptor. The results of many experiments confirmed that the sphingomyelin
      cycle products induce cells death by the apoptotic pathway and enhance induced
      apoptosis. Ceramide and sphingosine regulate the activity of enzymes involved in
      transduction of apoptosis signal (protein kinases. Phosphatases, and proteases)
      and act as second messengers in transduction of the apoptosis signal.

PMID- 9609950
TI  - [Large-scale DNA fragmentation during apoptosis: is genome cleaved at boundaries
      of the topological domain?].
AB  - Published data demonstrating DNA cleavage to large fragments (tens kb) at the
      initial stages of apoptosis are critically reviewed. The presented data suggest
      specific pattern of such cleavage reflecting the general principle of eukaryotic
      genome arrangement in functional domains.

PMID- 9609951
TI  - [The role of apoptosis in the thymic involution during growth of the syngeneic
      transplanted tumor in mice].
AB  - Thymic involution accompanies the growth of many human and animals tumors but the
      precise mechanism of this phenomenon is unknown. We tried to elucidate the role
      of apoptosis as a possible mechanism of thymic involution during tumor growth.
      The mice were inoculated subcutaneously with syngeneic hepatoma 22a cells.
      Starting from the 3rd week after tumor inoculation, progressive thymic involution
      was observed. Histological studies revealed distinct delymphatization of the
      thymic cortex, reduced numbers of big lymphocytes in the subcapsular zone and of
      mitoses in the cortex, and an increased amount of mast cells. This was followed
      by decreased DNA synthesis in vitro as measured from 3H-thymidine incorporation.
      The number of pycnoses in the cortex was two to three times that in the thymus of
      control animals. DNA gel electrophoresis did not reveal any signs of apoptosis in
      the thymocytes without preincubation. Within 2 h of in vitro incubation of the
      thymocytes taken on the 7th day after the tumor inoculation, spontaneous
      apoptosis was more expressed than in the thymocytes from intact mice. This may
      reflect different induction mechanisms of apoptosis in the thymocytes from the
      tumor bearing and control mice. We propose that the mechanism of thymic
      involution during tumor growth is related to inhibition of thymocytes'
      proliferation, impaired differentiation and enhanced intrathymic death caused by
      cytokine release from the nonlymphoid thymic population.

PMID- 9609952
TI  - [Comparative study of Ca/Mg-dependent nucleases from the mammalian thymus].
AB  - Ca/Mg-dependent nuclease is a possible key enzyme of apoptosis. We isolated and
      purified nucleases from the human and rat thymus to a homogeneous state and
      compared some properties of the obtained preparations with those of the earlier
      isolated Ca/Mg-dependent nuclease from the calf thymus. The activity of the
      nuclease from the human thymus in the presence of bivalent ions decreases in a
      sequence:(Ca + Mg) = (Ca + Mn) > Mn, that from the rat thymus: (Ca + Mn) > Mn >
      (Ca + Mg), and that from the calf thymus: (Ca + Mn) > (Ca + Mg) > Mn. Nuclease
      are not active in a medium containing only Mg, Ca, Co, and Zn ions. The
      preparations proved to be unstable during their isolation and storage. If the
      relative molecular mass of the purifies preparations was according to
      electrophoresis in 12% DS-Na-polyacrylamide gel 28, 29, and 18.4 and 21 kDa for
      the calf, human, and rat, respectively, after storage at -20 degrees C for two to
      six months, the molecular mass of native proteins decreases to 17-14 kDa. Some
      other properties of the enzymes have been described.

PMID- 9609953
TI  - [Cell sensitivity to Fas-mediated apoptosis depends on three forms of Fas
      antigen].
AB  - It is known that binding of specific anti-Fas antibodies to Fas-receptor induces
      apoptosis in various cell lines. But the mechanisms of functional regulation and
      realization of apoptosis remain so far unknown. We obtained HeLa cells
      transfected with cDNA of Fas-antigen, whose expression was located under the
      promoter controlled by isopropoyl beta-D-thiogalactopiranoside. Analysis of
      transfectants has shown that expression of Fas above a certain critical level
      leads to redistribution of Fas in the cells and is accompanied by changes in the
      cell cycles and cell sensitivity to the cytotoxic effects of anti-Fas and tumor
      necrosis factor (TNF). We propose that the sensitivity of cells to Fas-mediated
      apoptosis depends on the ratio of transmembrane, intracellular and soluble Fas
      antigen in the cells.

PMID- 9609954
TI  - [Mechanism of cell death in myeloma NS(O) in culture].
AB  - We studied in vitro myeloma cell death in a serum-free medium. Spectrophotometric
      assessment of DNA fragmentation, flow cytometry, and staining by Hoechst dye and
      ethidium bromide indicate that by the beginning of the third day cell death
      largely followed the apoptotic pathway. We studied dynamics of intracellular pH
      (pHi) during the cell death and the relationship between the pHi and apoptosis
      induction during cultivation in media with different pH. We have shown that
      decreasing pHi in the course of cell death is a consequence rather than the cause
      of myeloma cell death. Apoptosis took place at cultivation in the media with pH
      6.3 and 8.1; the corresponding pHi values were 6.5 and 7.2, respectively. In the
      presence of Ca-ionophore A23187 we observed appearance of the cells with aberrant
      distribution of chromatin and fragmented nucleus; however calcium binding in the
      media with 5-10 mM EDTA induced even more pronounced nuclei fragmentation. This
      may indicate that both increased and decreased concentration of intracellular
      calcium induce NS(O) myeloma cell apoptosis.

PMID- 9609955
TI  - [Signalling during radiation-induced apoptosis of thymocytes].
AB  - The mechanisms of signal triggering, enhancement and transduction during
      radiation-induced apoptosis of the thymocytes are discussed. Apoptosis is
      triggered by aggregation of receptors accompanied by activation of protein
      tyrosine kinases. The receptor aggregation is caused by radiation-induced cross
      links. The signal is transduced to the gene from protein tyrosine kinase through
      Ras-proteins, protein kinase C, and transcription factors. The necessity of the
      lipoxygenase gene expression and synthesis of this enzyme for support and
      enhancement of the apoptotic signal is postulated.

PMID- 9609956
TI  - [The role of cell interaction in initiation of radiation-induced death of
      thymocytes and apoptosis].
AB  - The experimental evidence of crucial importance of cell interactions for
      initiation of radiation-induced thymocyte death was obtained. It has been
      proposed that ionizing radiation, in contrast to many other cytotoxic agents,
      initiates thymocyte death simultaneously by different independent pathways,
      affecting all cellular components. The concept of apoptosis as "programmed cell
      death" has been critically discussed.

PMID- 9609957
TI  - [Increase in Ca(2+)-permeability of the plasma membrane during radiation-induced
      apoptosis of thymocytes].
AB  - The parameters of Ca(2+)-permeability (rate of Ca2+ influx in the presence of
      Ca(2+)-ATPase blocker vanadate and initial rate of Ca2+ uptake) were determined
      in the rat thymocytes after induction of apoptosis in vitro by gamma (gamma
      irradiation at 5 Gy. There were no changes in the rate of Ca(2+)-influx within 30
      to 909 min after irradiation, thus suggesting passive membrane permeability,
      while the initial rate of Ca(2+)-uptake, which characterizes Ca(2+)-exchange,
      approximately doubled in the irradiated cells. Thereafter, the initial rate of
      Ca(2+)-uptake in the intact and irradiated thymocytes became equal, while the
      rate of Ca(2+)-influx in the irradiated cells increased reliably 1.5-2 times
      within 90-180 min. Modification of membrane permeability for Ca2+ in the
      irradiated thymocytes precedes initiation of DNA degradation, and passive
      permeability is increasingly disturbed as apoptosis progresses. These data
      suggest that disturbances in Ca2+ passive permeability and intracellular Ca2+
      homeostasis are an apoptosis trigger in lethally irradiated thymocytes.

PMID- 9609958
TI  - [Apoptosis of cells of the bone marrow hematopoietic tissue during acute
      radiation damage in humans and experimental animals].
AB  - We studied the bone marrow of various localization taken during autopsy of the
      humans died as a result of accident at the Chernobyl Nuclear Power Station and
      experimental animals (frogs and rats) subject to external gamma (gamma
      irradiation at lethal doses (SD 100). It was shown using histological,
      histochemical and electronmicroscopic methods that the early radiation death of
      the bone marrow hemopoietic cells, so-called "early necrobiosis", is realized by
      apoptosis. During the period of recovery, apoptotic death of the hemopoietic
      cells also takes place, which, being expressed simultaneously with the onset of
      hemopoiesis, directly correlates with the intensity of repair. It was proposed
      that apoptosis as a physiological contrast of mitosis, arises during the early
      postradiation period as a response to blockade of mitotic activity and causes its
      abortive rise and bone marrow cellularity. During the recovery period, apoptosis
      may not only passively accompany mitosis but stimulate proliferative processes.

PMID- 9609959
TI  - [Proliferation and death of thymocytes caused by phospholipase A2 activator-
      melittin].
AB  - The effects of mellitin, a component of bee venom activating phospholipase A2, on
      proliferation and death of the rat thymocytes were studied in a wide
      concentration range. Cell proliferation was estimated by the accumulation of
      colchicine metaphases, Necrosis was estimated by cell lysis and Trypan blue
      staining. Apoptosis was estimated by the type of DNA fragmentation, amount of
      fragmented DNA, and percentage of cells with hypodiploid DNA set. Low
      concentrations of mellitin (below 5 micrograms/ml) stimulated proliferation. At
      higher mellitin concentrations, the thymocytes die by the primary necrosis type.
      Mellitin did not induce apoptosis in the thymocytes within the concentration
      range used: on the contrary, at high concentrations, it inhibited apoptosis of
      the thymocytes in the control and after irradiation. Actinomycin D, inhibitor of
      RNA synthesis, exerted no effect on the thymocyte death in the presence of
      mellitin. It has been concluded that activation of phospholipase A2 may induce
      necrosis, rather than apoptosis, and consequently, activation of phospholipase A2
      is not a necessary step in the signalling cascade that initiated apoptosis in the
      thymocytes.

PMID- 9609960
TI  - [Variable changes in immune reactivity and stress-sensitivity as a factor of
      selection of adaptation strategy under unfavorable conditions].
AB  - Experimental data are provided which substantiate the concept on reciprocal
      changes in immune reactivity and stress sensitivity as a basis for selection of
      adaptation strategy under unfavorable conditions. The data obtained suggest that
      transition from the resistant (stress) strategy of adaptation to hypobiosis is a
      prerequisite for maintenance of the immune reactivity under extreme conditions.
      Stimulation of the immune system per se may provide for transition from stress to
      the tolerant (hypobiotic) strategy of adaptation.

PMID- 9609961
TI  - [Changes in reactivity of the contractile system of the small intestine caused by
      disturbed parasympathetic innervation].
AB  - We studied the role of parasympathetic division of vegetative nervous system in
      regulation of the intestine activity in rats subjected to bilateral
      subdiaphragmal vagotomy, the response of the neuromuscular apparatus of the small
      intestine to stimulation by aceclydine taken as an example. Intravenous injection
      of aceclydine (0.5 mg/kg) into intact animals is accompanied by characteristics
      changes in the electrical and contractile activities of the intestine, which
      reflect its enhanced motor activity. Vagotomy leads to changes of response of the
      intestine to pharmacological stimulation, most expressed within 3, 7, and 30
      days. It was proposed that distortion of reactive properties of the intestine
      contractile system under these conditions is related to functional changes in
      rhythm-setting neurons of intramural ganglia and M-cholinoreceptors of
      neuromuscular synapses.

PMID- 9609963
TI  - Antiretroviral therapy, 1998.
AB  - In summary, during 1996 and 1997 important improvements occurred in HIV therapy.
      The introduction of new drugs benefited patients with access to these
      medications. The use of antiretrovirals remains complex and is rapidly evolving.
      This is an inspiring challenge for physicians and health workers caring for HIV
      infected patients.

PMID- 9609962
TI  - [Prevention of nitric oxide hyperproduction by adaptation to stressor effects].
AB  - As was shown earlier, acute hypotensive shock induced by nitrogen oxide (NO)
      hyperproduction can be prevented by dosed adaptation to environmental factors. In
      this work we tested the hypothesis that the mechanism of this adaptive effect is
      based on limiting NO hyperproduction. It was shown that rat adaptation to stress
      completely prevented arterial depression and sharply increased revival rate of
      the animals after heat shock. Hypotension induced by heat shock was accompanied
      by almost 2.5-fold increase in NO production (EPR analysis) as compared to the
      control. At the background of preadaptation, heat shock did not increase NO
      production relative to the animals not subjected to heat shock. The data obtained
      agree with the proposal that the adaptation initiates NO-dependent mechanisms of
      limiting NO hyperproduction. Such limiting seems to be negatively regulated by
      NO.

PMID- 9609964
TI  - Dynamic stereotactic radiosurgery: the Charleston program: a report on the first
      150 patients.
AB  - We have been pleased with our initial experience in an evolving program. As newer
      surgical and radiotherapy techniques have become available, the role of
      radiosurgery has been and will continue to be modified. As more commercially
      available systems have been marketed, the availability will become more
      widespread. A battery of residents in neurosurgery and radiation oncology trained
      in these technologies will provide leadership and future directions of this
      therapy.

PMID- 9609965
TI  - The medical workforce in South Carolina: its current status and a look to the
      future.
AB  - Available data suggest that South Carolina does not have the same degree of
      problems with its medical workforce as is present in many other areas of the
      country. While there may be too many specialists and not enough primary care
      physicians and while maldistribution is also a problem in some areas of the
      state; it appears that the total number of physicians and the size and focus of
      the medical education system in South Carolina are about what they should be.
      Furthermore, the graduate medical education system in South Carolina is currently
      changing on its own to emphasize more primary care and less specialist training.
      With careful monitoring, coordination of effort, and specific initiatives to
      address specialty, maldistribution and curricular issues, the state's medical
      education programs can take action to build on their current strengths and assure
      a medical workforce of sufficient size, type, and skill to meet the future needs
      of the citizens of South Carolina.

PMID- 9609966
TI  - Rightsizing the healthcare workforce.

PMID- 9609967
TI  - [Factor impact and indexing in bibliographic databases: comparison of these
      quality criteria for the assessment of pharmaceutical journals].
AB  - In spite of limits, the impact factor (IF) of Journal Citation Reports (JCR) of
      Science Citation Index (SCI) edited by the Institute for Scientific Information
      (ISI) is the most currently used bibliometric factor by scientists. Otherwise,
      bibliographic systems select and index scientific journals with their own quality
      criterion. In order to bring scientists and information professionals some new
      journal evaluation developments, we studied and compared pharmaceutical journal
      IF and the number of bibliographic systems in which they were indexed. We firstly
      have given our definition of pharmaceutical journal and then evaluated these
      journals by giving one point each time they were indexed in one of the five
      following bibliographic systems: Index Medicus/Medline, Excerpta Medica/Embase,
      International Pharmaceutical Abstracts, Chemical Abstracts, Current Contents. We
      then compared their results with IF. We selected 292 journals: 14.4% scored 5
      points, 22.3% scored 4 points, 27.7% scored 3 points, 18.8% scored 2 points,
      16.8% scored 1 point. We also showed that the more journals scored highly, the
      more they had chances of being taken by JCR. We studied the first hundred
      journals indexed by JCR and having the highly IF: 31, 40, 21, 6 and 2 journals
      were respectively indexed by 5, 4, 3, 2 and 1 bibliographic systems. We showed
      that there was a significant difference between the two classifications. So, we
      can say that people who take IF as the one and only journal quality criterion
      have in fact a very partial representation of the edition of scientific papers.

PMID- 9609968
TI  - Influence of stearylamine and dicetylphosphate on the physical properties of
      submicron O/W emulsions.
AB  - Stearylamine and dicetylphosphate were added to glycerol or sorbitol isotonised
      sunflower oil, soybean oil and medium chain triglyceride (MCT) oil-in-water
      submicron emulsions stabilised using egg yolk and soybean lecithins, and blends
      of polysorbate/sorbate with the aim to induce positive and negative electrical
      charges. Glycerol isotonized emulsions containing 0.3% (w/w) stearylamine could
      only be obtained when lecithins dosing up to 80% (w/w) phosphatidylcholine (PC)
      were employed, but they did not resist to long term storage up to 90 days.
      Sorbitol isotonized stearylamine emulsions were achieved only with lecithins
      having a PC content superior to 90% (w/w) without more resistance to storage.
      Stearylamine did not influence the stability of emulsions prepared with non-ionic
      emulsifiers. So, the destabilising effect of stearylamine on emulsions prepared
      with lecithins could be due to interaction of its cationic group with anionic
      lipids and was not related to the nature of the oil. Dicetylphosphate did not
      markedly affect emulsions supporting further the hypothesis of interaction of
      stearylamine with lecithin phospholipids.

PMID- 9609969
TI  - Protective effect of cysteine and vitamin E, Crocus sativus and Nigella sativa
      extracts on cisplatin-induced toxicity in rats.
AB  - Cisplatin [cis-dichlorodiammineplatinum (II)] is a widely used chemotherapeutic
      drug that is toxic to the kidney. Concurrent administration of cysteine together
      with vitamin E, Crocus sativus and Nigella sativa reduced the toxicity of
      cisplatin in rats. When administered i.p. for 5 alternate days with 3 mg/kg
      cisplatin, cysteine (20 mg/kg) together with vitamin E (2 mg/rat) an extract of
      Crocus sativus stigmas (50 mg/kg) and Nigella sativa seed (50 mg/kg)
      significantly reduced blood urea nitrogen (BUN) and serum creatinine levels as
      well as cisplatin-induced serum total lipids increases. In contrast, the
      protective agents given together with cisplatin led to an even greater decrease
      in blood glucose than that seen with cisplatin alone. The serum activities of
      alkaline phosphatase, lactate dehydrogenase, malate dehydrogenase, aspartate
      aminotransferase and alanine aminotransferase of cisplatin-treated rats were
      significantly decreased, whereas the activities of glutathione reductase and
      isocitrate dehydrogenase were significantly increased. Addition of cysteine and
      vitamin E, Crocus sativus and Nigella sativa in combination with cisplatin
      partially prevented many changes in the activities of serum enzymes. In cisplatin
      treated rats, the liver activities of isocitrate dehydrogenase and aspartate
      aminotransferase were significantly increased, whereas much greater changes were
      found in the kidneys, with increased activity of glucose-6-phosphate
      dehydrogenase and decreased activities of alkaline phosphatase, isocitrate
      dehydrogenase, malate dehydrogenase, aspartate aminotransferase, alanine
      aminotransferase, sorbitol dehydrogenase and gamma-glutamyl transferase, as well
      as a decreased phosphorylation to oxidation ratio in the mitochondria, indicating
      reduced adenosine triphosphate production. Also, administration of cysteine and
      vitamin E, Crocus sativus and Nigella sativa together with cisplatin partially
      reversed many of the kidney enzymes changes induced by cisplatin. Cysteine
      together with vitamin E, Crocus sativus and Nigella sativa tended to protect from
      cisplatin-induced falls in leucocyte counts, haemoglobin levels and mean osmotic
      fragility of erythrocytes and also prevented the increase in haematocrit. The
      results of this study indicate a basis for the toxic effects of cisplatin, and
      suggest a possible way of counteracting the toxicity by introducing protective
      agents such sulphydryl compounds, other antioxidants and extracts of natural
      products. It also appears that cells adapt to the effects of cisplatin through
      the induction of systems that produce NADPH, which in turn compensates the
      decrease of free sulphydryl groups. We conclude that cysteine and vitamin E,
      Crocus sativus and Nigella Sativa may be a promising compound for reducing
      cisplatin-toxic side effects including nephrotoxicity.

PMID- 9609970
TI  - Men, masculinity, and health behavior.

PMID- 9609971
TI  - College students' binge drinking at a beach-front destination during spring
      break.
AB  - Four hundred forty-two women and 341 men were surveyed at Panama City Beach,
      Florida, to assess the effects of gender, age, fraternity or sorority membership,
      and travel motivation on alcohol consumption and binge drinking during spring
      break. The mean number of drinks consumed the previous day was 18 for men and 10
      for women; 91.7% of the men and 78.1% of the women had participated in a binge
      drinking episode during the previous day. Respondents less than 21 years old
      consumed less alcohol and reported significantly lower frequencies of
      intoxication than those over 21. The men's reported levels of alcohol
      consumption, binge drinking, and intoxication to the point of sickness were
      significantly higher than the women's, but fraternity or sorority membership was
      not associated with higher levels of consumption. Students motivated to visit the
      specific destination because of its "party" reputation consumed significantly
      more alcohol than students who cited other reasons for going there.

PMID- 9609972
TI  - Alcohol use and related consequences among students with varying levels of
      involvement in college athletics.
AB  - Alcohol use, binge drinking, and substance abuse-related consequences among
      students with varying levels of participation in intercollegiate athletics were
      examined. Between October 1994 and May 1996, 51,483 students at 125 institutions
      answered questions about their involvement in athletics, ranging from
      noninvolvement to participant to leadership positions, on the long form of the
      Core Alcohol and Drug Survey. In comparisons with nonathletes, both male and
      female athletes consumed significantly more alcohol per week, engaged in binge
      drinking more often, and suffered more adverse consequences from their substance
      use. No support was found for the hypothesis that athletic leaders were more
      responsible than other team participants in using alcohol. Male team leaders
      appeared to be at significantly greater risk than female team leaders; they also
      consumed more alcohol, binged more often, and suffered more consequences than
      other team members.

PMID- 9609973
TI  - Health risk taking and human immunodeficiency virus risk in collegiate female
      athletes.
AB  - Risky health behaviors of female intercollegiate varsity athletes and their
      nonathlete peers were compared. Five hundred seventy-one female university
      students (109 athletes and 462 nonathlete peers) at two midwestern universities
      completed a self-administered, anonymous questionnaire during team meetings or
      class sessions. Each athlete was matched with two nonathlete controls of similar
      age, ethnicity, and class year to test for dichotomous outcome variables. A human
      immunodeficiency virus (HIV) risk scale was developed to identify factors
      associated with increased HIV risk for all of the female participants. Measures
      of alcohol and other drug use were associated with HIV risk. The athletes were
      found to engage in significantly fewer risk-taking behaviors than the nonathletes
      and to be at less risk for HIV. High levels of risk behaviors generally indicated
      the need for increased efforts to change risky behaviors in all college women.

PMID- 9609974
TI  - Over-the-counter psychotropics: a review of melatonin, St John's wort, valerian,
      and kava-kava.
AB  - Use and availability of alternative healthcare products have revived in the last
      few years. The prevalence of supplement use in the United States is largely
      unknown but is thought to be widespread. In this article, four of the common
      substances used to treat emotional problems are reviewed. The plant or substance
      description, clinical indications, evidence of therapeutic efficacy, mechanisms
      of therapeutic actions, dosages and regimens, different commercially available
      preparations, and adverse effects and toxicities are described for melatonin, St
      John's wort, valerian, and kava-kava. That a product is "natural" does not mean
      that it is either safe or effective. Many supplements are potent drugs that lack
      sufficient data on safety, dose-response relationships, drug interactions, and
      purity.

PMID- 9609975
TI  - College men's health: an overview and a call to action.
AB  - For men of college age, the risks of disease, injury, and death are far greater
      than for women of the same age group, yet college men's health concerns receive
      little attention from health professionals. In this multidisciplinary overview,
      the author discusses college men's health risks, men's failure to adopt health
      promoting behaviors, their propensity to engage in risky behaviors, their beliefs
      about manhood, their attitudes concerning their own vulnerability, and their
      limited knowledge about health. Men's socialization as boys is discussed to
      provide a framework for understanding why many college men have adopted unhealthy
      lifestyles. How masculinity and stereotypes about manhood influence the health
      services provided for men are outlined. The importance of providing gender
      specific health behavior interventions and programs is stressed, and implications
      for future research are offered.

PMID- 9609976
TI  - Analysis of weapon carrying among college students, by region and institution
      type.

PMID- 9609977
TI  - The proliferation and differentiation of neonatal epidermal melanocytes in F1
      hairless mice of HR-1 x HR/De in serum-free culture.
AB  - To investigate the characteristics of the proliferation and differentiation of
      epidermal melanocytes in F1 hairless mice of HR-1 x HR/De parents in vitro, cell
      suspensions of the neonatal epidermis were cultured in a serum-free medium
      supplemented with dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP) and/or
      basic fibroblast growth factor (bFGF). The differentiation of melanocytes was
      induced by treatment with DBcAMP. In contrast, the sustained proliferation of
      melanoblasts was induced by combined treatment with DBcAMP and bFGF. The
      melanoblasts could be subcultured in serum-free medium supplemented with the two
      factors in the presence of keratinocytes, but not in their absence. This is the
      first report of successful culture of melanoblasts and melanocytes from hairless
      mice; it is expected to be useful in understanding the mechanism of the
      development of pigmented spots in the epidermis of (HR-1 x HR/De)F1 mice, which
      are reported to be induced by repeated exposure to ultraviolet light B.

PMID- 9609978
TI  - Ultrastructural observation of platelets from patients with progressive systemic
      sclerosis (PSS).
AB  - We observed the ultrastructure of platelets from patients with PSS (7 cases; 48.2
      +/- 12.3 y-old; M:F = 1:6_ and healthy controls (HC) (5 cases; 44.8 +/- 8.0 y
      old; M:F = 1:4) by using transmission (TEM) and freeze-fracture electron
      microscopy (FEM). The open canalicular system (OCS) connected with the plasma
      membrane (PM) formed pinhole-like invaginations (50 nm in diameter) in the
      cleaved face (P-face) of the plasma membrane seen from the outside of the
      platelets and sharply elevated structures in the cleaved face (E-face) of PM seen
      from the inside of the platelets by FEM. The density of OCS on the surface of the
      platelets from PSS patients was 3 +/- 1/micron 2, which was higher than that from
      HC (1 +/- 0.5/micron 2) (p < 0.02). Dome-shaped structures, which clearly differ
      from OCS and were 80-150 nm in diameter without intramembranous particles, were
      seen in the P-face, and the complementary depressed structures were seen in the E
      face. These structures were thought to be vesicles fused onto the PM of the
      platelets. The total volume of platelets (7.62 +/- 0.11 micron 3), total volume
      of granules (0.79 +/- 0.01 micron 3) and vacuoles including OCS (0.78 +/- 0.05
      micron 3), and the total surface area of platelets (17.25 +/- 1.30 micron 2) from
      four PSS patients calculated by the morphometrical method were similar to those
      from four HC (7.32 +/- 0.25 micron 3, 0.76 +/- 0.03 micron 3, 0.80 +/- 0.05
      micron 3, 18.75 +/- 0.35 micron 2, respectively); there were no statistical
      significances between the data from PSS patients and HC. The total volumes of
      vacuoles in platelets from both PSS patients and HC significantly decreased after
      a 2 min-vibration stress of the hands (p < 0.02) and the total volume of granules
      in platelets from PSS patients decreased significantly after the same stress (p <
      0.002), although that from HC showed no similar significant change. However,
      there were no statistically significant differences in total volume or total
      surface of platelets from PSS patients and HC after the stress. These data may
      suggest that depletion of granules occurred due to activation of platelets from
      PSS patients following a secretion of their proteins, because their plasma
      protein levels were elevated after the stress (Jpn J Dermatol, 98; 1205, 1988).
      Higher density of OCS on the surface of the platelets from PSS patients may play
      an important role in secretion of their proteins, although the detailed mechanism
      of secretion of specific proteins derived from platelet granules is still
      unknown. These ultrastructural abnormalities of platelets may correlate with some
      involvement of a platelet disorder and with a possible role for the activation of
      platelets from PSS patients.

PMID- 9609979
TI  - Topical anthralin therapy for refractory nail psoriasis.
AB  - The nail is commonly involved in psoriasis; however, very few therapies are
      satisfactory. In this study, we treated for 20 cases of psoriasis vulgaris with
      nail involvement with topical anthralin therapy. An ointment of 0.4-2.0%
      anthralin in petrolatum was applied to the affected nail bed once a day and
      washed away with water after 30 minutes. Then, 10% triethanolamine cream was
      applied to prevent undesired pigmentation. Within five months of therapy, twelve
      out of twenty psoriatic patients (60%) showed moderate and obvious improvement,
      four patients (20%) showed no response to this regimen. Onycholysis and
      pachyonychia both responded clinically, and the number of pitting was markedly
      decreased in some cases. The main side effect of anthralin therapy was reversible
      pigmentation of the nail plate. Topical anthralin therapy is effective for nail
      psoriasis and considered to be a useful treatment for refractory nail psoriasis.

PMID- 9609980
TI  - Treatment of cutaneous leishmaniasis by direct current electrotherapy: the
      Baghdadin device.
AB  - Electrical stimulation has been used as a mode of therapy for a number of
      clinical conditions. However, it has not been used for the treatment of cutaneous
      leishmaniasis (CL). For this purpose, we designed the "Baghdadin device". A total
      of 146 lesions of acute CL in 54 patients were treated by this device. Twenty-one
      lesions in the same patients were left untreated as controls. In addition, 36
      lesions in 15 patients were treated with intralesional sodium stibogluconate.
      Treatment by the Baghdadin device consisted of weekly sessions of 10 minutes of
      direct current electrical stimulation. The intensity of the direct current ranged
      between 5 and 15 milliamperes, and the voltage was kept below 40 volts. Of the
      146 lesions, 135 (92.5%) showed total clearance or marked improvement in 4-6
      weeks time. Approximately 67% of the lesions needed only one or two sessions.
      Scarring was not observed after resolution. None of the untreated lesions showed
      any signs of improvement in 6 weeks. Of the lesions treated with sodium
      stibogluconate, 32 lesions (88.9%) showed total clearance or marked improvement,
      which was not significantly different from the results with the Baghdadin device.

PMID- 9609981
TI  - High incidence of IgG antibodies to phenolic glycolipid in non-leprosy patients
      in India.
AB  - Purified phenolic glycolipid (PGL-1) from Mycobacterium leprae was used to detect
      IgG antibodies against PGL-1 in leprosy patients in an enzyme-linked
      immunosorbent assay (ELISA). A total of 698 sera were screened; they came from
      patients suffering from leprosy, autoimmune disease, myeloma, tuberculosis and
      sexually transmitted diseases (STDs). Cases with miscellaneous diseases and
      persons undergoing AIDS screening were also included. Sera from lepromatous and
      tuberculoid leprosy patients gave positivity rates of 60.5% and 41.7%,
      respectively. In non-leprosy cases, the PGL-1 ELISA showed an overall positivity
      rate of 6.9%; this was greatest in patients with tuberculosis (43.8%) followed by
      autoimmune diseases (40.9%) and miscellaneous cases including liver diseases
      (37.9%). This study emphasizes that PGL-1 ELISA has a low predictive value for
      diagnosis of active infection by Mycobacterium leprae. Positive reactions in a
      significant percentage of patients with autoimmune disease are intriguing and
      need indepth study.

PMID- 9609982
TI  - Pyodermia chronica glutealis complicated by acromegalic gigantism.
AB  - We report a case of pyodermia chronica glutealis complicated by acromegalic
      gigantism associated with hyperprolactinemia. The serum prolactin, growth
      hormone, adrenocorticotropic hormone, and 11-deoxycortisol levels were elevated,
      but the estradiol and dehydroepiandrosterone-sulphate levels were within normal
      limits. However, the testosterone level was very low. Histopathologically, we
      found sinus tracts and scarring in a specimen from the buttocks. We could not
      immunohistochemically detect clear androgen, growth hormone, or prolactin
      receptors at any site. The patient was a man with a height of 197 cm and weight
      of 140 kg, he had clinical features of active acromegaly such as excessive
      sweating and increased thickness of soft tissue. He was also diagnosed with
      diabetes mellitus. Under such conditions, bacteria could easily grow and lesions
      might have been aggravated by the heavy pressure from his weight, a possible
      causes of his pyodermia chronica glutealis.

PMID- 9609983
TI  - A case of bullous pemphigoid in a patient on hemodialysis.
AB  - We describe a case of bullous pemphigoid (BP) in a patient with chronic renal
      failure maintained on hemodialysis. We diagnosed BP by histopathological and
      immunofluorescence studies. The relationship between BP and chronic renal failure
      and/or hemodialysis is not clear, but we believe that immune disarrangement due
      to chronic renal failure and/or hemodialysis may have influenced the pathogenesis
      of BP in our case.

PMID- 9609984
TI  - Suplatast tosilate (IPD), a new immunoregulator, is effective in vitiligo
      treatment.
AB  - The major type of vitiligo is considered to be an autoimmune disorder. Anti
      melanocyte antibodies are frequently detected in sera of patients with this
      disease. Interleukin (IL)-4 released from Th2 cells is an important factor in
      stimulating autoantibody production by B-cells. In this study, seven patients
      with vitiligo treated with suplatast tosilate (IPD), three showed repigmentation
      and improvement of their lesions after administration of the drug. IPD halted the
      continuous spread of the lesions in three of the other patients, and, in two of
      them, also reduced microsome test and thyroid test titers. The efficacy of IPD in
      treating vitiligo was thought to be due to the suppressive effect of this drug on
      IL-4 production. No side effect was observed. Thus IPD may represent a new
      alternative in vitiligo treatment due to its inhibition of autoimmunity by the
      suppression of IL-4.

PMID- 9609985
TI  - Metastasis of esophageal carcinoma manifesting as whitlow-like lesions.
AB  - A rare case of phalangeal metastasis of esophageal carcinoma in an 81-year-old
      man is described. The patient developed a tender, red, and swollen right index
      finger. From the clinical features, he was erroneously diagnosed with whitlow at
      first and treated with antibiotics with no success. A bone X-ray showed that the
      distal phalanx of the index finger was completely dissolved. Histopathological
      examination revealed proliferation of squamous cell carcinoma into the deep
      dermis. It is important to understand that the phalangeal metastases commonly
      display inflammatory symptoms that mimic acute infection.

PMID- 9609986
TI  - Two cases of unilateral axillary Paget's disease.
AB  - We herein report two cases of unilateral axillary Paget's disease. Extramammary
      Paget's disease commonly occurs in the anogenital area. Unilateral axillary
      occurrence is relatively rare. One defect was reconstructed with a pedicled
      scapular flap, and the other was reconstructed with split-skin graft after
      excision of the tumor. No recurrence was seen in either patient three years
      postoperatively. However, although the patient who had been reconstructed with a
      pedicled flap recovered uneventfully, the other patient, who had been
      reconstructed with a split-skin graft, suffered from axillary contracture due to
      the shrinkage of the grafted skin after surgery. A skin graft requires fixation
      for a long period to prevent shrinkage, which causes axillary contracture.
      Therefore, from the viewpoint of quality of life, reconstruction using flaps is
      recommended for axillary lesions.

PMID- 9609987
TI  - Pretibial myxedema with Graves' disease: a case report and review of Japanese
      literature.
AB  - We report a case of pretibial myxedema with Graves' disease in an 18-year-old
      Japanese woman. The physical examination revealed waxy indurated plaques with
      prominent hair follicle openings and nonpitting edema disseminated on her lower
      legs. Histology from an edematous lesion revealed that the dermis was markedly
      thickened with abundant mucin, especially hyaluronic acid, and the collagen
      fibers in this portion were splitting up into fibrils. We also reviewed 112 cases
      of pretibial myxedema reported in the Japanese literature.

PMID- 9609989
TI  - A case of seborrheic keratosis distributed along skin cleavage lines.
AB  - A 65-year-old woman with seborrheic keratosis following skin cleavage lines is
      reported. The mostly brownish-yellow lesions were located on the back. The round,
      oval, spindle, comet, and slightly raised papules varied from 1 mm to 2 cm in
      diameter. The distribution of lesions was unusual; they tended to follow skin
      cleavage lines on her lower back and waist. The arrangement of lesions was
      streamlined. The skin biopsy specimen revealed hyperkeratosis, acanthosis, and
      papillomatosis. The acanthosis was caused by proliferation of squamous and
      basaloid cells.

PMID- 9609988
TI  - Generalized erythematous skin eruptions due to trimethoprim itself and co
      trimoxazole.
AB  - A 20-year-old Japanese woman (Case 1) and a 70-year-old Japanese man (Case 2)
      consulted us with slight fever and disseminated erythematous papules.
      Examinations revealed that the first case was a skin eruption due to trimethoprim
      itself and the second was due to both trimethoprim and sulphamethoxazole. To our
      knowledge, our Case 1 is the first reported case with an erythematous papular
      type skin eruption caused by trimethoprim itself, and our Case 2 is the first
      case of a skin eruption in reaction to both trimethoprim and sulphamethoxazole.

PMID- 9609990
TI  - Pseudo-ainhum in discoid lupus erythematosus.

PMID- 9609991
TI  - Human autoimmune lymphoproliferative syndrome, a defect in the apoptosis-inducing
      Fas receptor: a lesson from the mouse model.
AB  - The immune response is regulated not only by the proliferation, differentiation,
      and activation of cells, but also by programmed cell death, called apoptosis. Fas
      ligand expressed in activated T cells binds to its receptor, Fas, and induces
      apoptosis in target cells. Two mouse mutations that cause autoimmune disease, lpr
      (lymphoproliferation) and gld (generalized lymphoproliferative disease), are
      mutations in Fas and FasL genes, respectively. Human patients showing phenotypes
      (Canale-Smith syndrome or autoimmune lymphoproliferative syndrome) similar to
      those in lpr mice also carry mutations in Fas. This is a good example of a case
      in which the identification of a mouse mutation has led to the understanding of a
      human disease.

PMID- 9609992
TI  - Identification by differential display of eight known genes induced during in
      vivo intimal hyperplasia.
AB  - To achieve a better understanding of the mechanism of intimal thickening, we used
      a rabbit model in which aorta was denuded mechanically by a balloon catheter.
      Total RNA was prepared from each aorta 1, 2, 7, 14, 23, or 30 days after
      denudation, and from intact aorta of non-denuded control rabbits. Subsequently,
      using the differential display method, we identified eight genes that were
      expressed differently during the time course after injury. One of them, RESP18
      (encoding regulated endocrine secretory protein 18), was suppressed during the
      acute reaction. The other seven showed increase in expression during the acute
      phase: the genes for hTAFII68 (human TATA-binding protein associated factor),
      NPAT (nuclear protein mapped to the AT locus), OSF2 (osteoblast-specific factor
      2), Pyst1, casein kinase 1 alpha, integrin alpha 1, and XP-C complementing
      protein. Although hTAFII68, NPAT, OSF2, and Pyst1 are thought to be related to
      transcription, not all four are positive regulators. Considering that none of
      these genes had previously been reported as being implicated in intimal
      hyperplasia, we conclude that many known or unknown genes play roles in this
      process. We believe that differential display is an effective method for
      screening genes whose variations in expression can provide clues toward
      understanding the molecular mechanism of intimal hyperplasia.

PMID- 9609993
TI  - An HLA-binding-motif-aided peptide epitope library: a novel library design for
      the screening of HLA-DR4-restricted antigenic peptides recognized by CD4+T cells.
AB  - Susceptibility to a series of autoimmune diseases is strongly associated with
      particular HLA class II alleles. Identification of T cell clones and antigenic
      epitopes bound by HLA class II molecules involved in autoimmune diseases is
      critical to understanding the etiology of these HLA class II-associated diseases.
      However, establishment of T cell clones in autoimmune diseases is difficult
      because the antigenic peptides are unknown. Peptide library methods which include
      all possible peptide sequences offer a potentially powerful tool for the
      detection of cross-reactive antigenic peptides recognized by T cells. Here, we
      reduced the number of peptides per mixture by utilizing the known binding motifs
      of peptides for the HLA-DRB1*0405 molecule and evaluated the effectiveness of
      this library design. Each library mixture evoked a strong proliferative response
      in the unprimed peripheral blood lymphocytes (PBL) from HLA-DRB1*0405-positive
      donors but little or no response in the PBL from HLA-DRB1*0405-negative donors.
      The library also detected antigenic peptides that activated three antigen
      specific T cell lines restricted by HLA-DRB1*0405, with different specificities.
      The motif-based approach thus presents a powerful method for monitoring T cells
      in large, heterogeneous T cell populations and is useful for the identification
      of the mimic peptide epitopes of T cell lines and clones.

PMID- 9609994
TI  - Refinement of the gene locus for autosomal recessive juvenile parkinsonism (AR
      JP) on chromosome 6q25.2-27 and identification of markers exhibiting linkage
      disequilibrium.
AB  - Autosomal recessive juvenile parkinsonism (AR-JP) (MIM 600116) is a hereditary
      neurodegenerative disorder characterized by levodopa-responsive parkinsonism with
      a mean age at onset of 23.2 years. We recently mapped the AR-JP gene locus to a
      17-cM interval on chromosome 6q25.2-27. To further narrow the candidate region of
      the AR-JP gene, we performed detailed linkage analysis using densely placed
      genetic markers in this region (D6S437, D6S1581, D6S1579, D6S305, D6S411, SOD2,
      D6S253, D6S1599, D6S1719 and D6S264). Pairwise linkage analysis revealed the
      highest cumulative maximal lod score of 9.13 at D6S1579 (theta = 0.05), and
      multipoint linkage analysis revealed the highest cumulative lod score of 12.4 at
      the locus 3 cM telomeric to D6S1599. Observation of obligate recombination events
      narrowed the candidate region to a 13-cM region between D6S1579 and D6S264.
      Furthermore, we identified two marker loci, D6S1579 and D6S1599, which exhibit
      strong linkage disequilibrium with the AR-JP locus: chi 2 (2 x n table) = 84.22;
      P < 0.0001, chi 2 [likelihood-ratio test (LRT)] = 20.66; P < 0.0001, lambda =
      0.40 and chi 2 (2 x n table) = 63.37; P < 0.0001, chi 2 (LRT) = 10.32; P <
      0.0001, lambda = 0.30, respectively. These results suggest that the candidate
      region for the AR-JP gene is most likely located near the 4-cM region
      encompassing D6S1579 and D6S1599.

PMID- 9609995
TI  - The gene for mesomelic dysplasia Kantaputra type is mapped to chromosome 2q24
      q32.
AB  - Mesomelic dysplasia Kantaputra type (MDK) (MIM *156232) is a new autosomal
      dominant skeletal dysplasia characterized by dwarfism, shortening of the
      forearms/lower-legs, carpal/tarsal synostosis, and dorsolateral foot deviation.
      We studied a Thai family in which 15 members in 3 generations were affected with
      MDK. With reference to the breakpoints of a balanced translocation
      [t(2;8)(q31;p21)] in patients from a previously reported Italian family with a
      skeletal dysplasia that appears similar to MDK, a linkage analysis was performed
      in the Thai family using 50 CA-repeat markers mapped to nearby regions (2q22-q34
      and 8p24-p21) of the translocation breakpoints. The results clearly ruled out a
      linkage of MDK to marker loci at the 8p24-p21 region, whereas all nine affected
      members available for the study shared a haplotype at four loci (D2S2284, D2S326,
      D2S2188, and D2S2314) spanning about 22.7 cM in the 2q24-q32 region. The computer
      assisted two-point linkage analysis revealed maximum logarithm of odds (lod)
      scores of 4.82, 4.21, 4.82, and 4.21 (theta = 0) at these loci, respectively.
      These data indicated that the MDK locus is in the vicinity of D2S2284 and D2S2188
      loci that are most likely mapped to 2q24-q32.

PMID- 9609996
TI  - -6A promoter variant of angiotensinogen and blood pressure variation in Canadian
      Oji-Cree.
AB  - We previously reported significant associations between variation in the AGT gene
      at codon 235 and both systolic pressure and hypertension in Canadian Oji-Cree.
      Recently, Inoue et al suggested that the AGT T235 variant was not causative, but
      was rather in linkage disequilibrium with a variant in the AGT promoter, namely 
      6A, that was associated with increased in vitro expression of angiotensinogen and
      was thus a strong candidate to be the functional basis of the previously observed
      associations. We genotyped 518 adult Oji-Cree for the AGT promoter polymorphism
      and tested for its association with blood pressure and hypertension. We found
      that the frequency of the -6A variant was 0.85 in the Oji-Cree, which is much
      higher than the frequency observed in other human samples. We also found strong
      linkage disequilibrium between the AGT -6A and T235 variants. However, genetic
      variation of the AGT promoter was only marginally associated with variation in
      systolic pressure, with a trend to significantly higher systolic pressure seen in
      AGT -6A/A homozygotes than in subjects with other genotypes. In addition, genetic
      variation of the AGT promoter tended to be associated with a diagnosis of
      hypertension. Despite the very high prevalence of -6A, our native sample was
      essentially normotensive. Our findings are consistent with a marginally
      deleterious effect of the AGT -6A allele on blood pressure, but linkage
      disequilibrium with another causative variant cannot be ruled out in this sample
      of aboriginal Canadians.

PMID- 9609997
TI  - High proportion of missense mutations of the BRCA1 and BRCA2 genes in Japanese
      breast cancer families.
AB  - Mutations in either of two recently identified genes, BRCA1 and BRCA2, are
      thought to be responsible for approximately two-thirds of all cases of autosomal
      dominantly inherited breast cancer. To examine the nature and frequency of BRCA1
      and BRCA2 mutations in Japanese families exhibiting a high incidence of breast
      cancer, we screened 78 unrelated families in this category for mutations of these
      two genes. Examining the entire coding sequences as well as exon-intron
      boundaries of both genes by polymerase chain reaction (PCR) single-strand
      conformation polymorphism (SSCP) and multiplex-SSCP analysis, we identified
      possible disease-causing alterations in BRCA1 among affected members of 15
      families and in BRCA2 in another 14 families. In 15 of those 29 families, the
      affected individuals carried missense mutations, although most germline mutations
      reported worldwide have been deletions or nonsense mutations. Our results,
      indicating that missense mutations of BRCA1 and BRCA2 tend to predominate over
      frameshifts or nonsense mutations in Japanese breast cancer families, will
      contribute significantly to an understanding of mammary tumorigenesis in Japan,
      and will be of vital importance for future genetic testing.

PMID- 9609998
TI  - In situ detection of insulin-like growth factor II (IGF2) and H19 gene expression
      in hepatocellular carcinoma.
AB  - To assess the relationship between insulin-like growth factor II (IGF2) and H19
      gene expression at the cellular level, we have examined the distribution of IGF2
      and H19 mRNA by means of an situ hybridization in hepatic malignancies consisting
      of hepatocellular carcinoma (HCC), cholangiocellular carcinoma (CCC), and
      metastatic liver cancer (MLC). In HCC, 15 of 27 tumors (56%) and 11 of 27 tumors
      (41%) demonstrated increased IGF2 and H19 gene expression, respectively. Of 16
      HCCs with increased expression of either IGF2 or H19, 10 tumors coexpressed both
      transcripts at comparable levels. Moreover, the spatiotemporal distribution and
      the cellular localization of the two gene transcripts were almost identical,
      suggesting the presence of a reciprocal relation between IGF2 and H19. In
      addition, 5 HCCs showed increased IGF2 expression without concomitant H19
      expression, whereas 1 HCC showed increased H19 expression without IGF2
      transcripts. However, 11 HCCs showed no IGF2 or H19 expression. On the other
      hand, neither IGF2 transcripts nor H19 transcripts were detected in 2 CCCs or 10
      MLCs studied. The data suggest that IGF2 and/or H19 gene expression may be
      characteristic of some HCCs.

PMID- 9609999
TI  - Expression analysis of two mutant human ornithine transcarbamylases in COS-7
      cells.
AB  - Ornithine transcarbamylase (OTC) is located in the mitochondrial matrix of the
      liver and small intestine and catalyzes the second step of the urea cycle. OTC
      deficiency (OTCD) is an X-linked inborn error of metabolism and causes
      hyperammonemia. We reported in 1992 the A152V and G195R mutations in patients
      with OTCD. These mutant OTC cDNAs were prepared by site-directed mutagenesis
      using the polymerase chain reaction (PCR). The wild-type and mutant cDNAs were
      transiently expressed in COS-7 cells. The wild-type cDNA gave an OTC activity of
      1180 +/- 47 nmol/min per mg protein. The OTC activities of the A152V and the
      G195R mutants were 3.7% and 2.5% of that of wild-type, respectively. Immunoblot
      analysis showed that the quantities of OTC proteins in the A152V and G195R
      mutants were 29% and 12% of that of wild-type, respectively. In pulse-labeling
      and pulse-chase experiments, the precursor form of OTC was synthesized and
      processed to the mature form. The A152V mutant OTC was processed to the mature
      form as rapidly as the wild-type precursor. However, the processed, mature form
      of the mutant OTC was rapidly degraded, presumably in the mitochondrial matrix.
      These results indicate that OTCD with the A152V mutation is due both to rapid
      degradation of the processed, mature form, and to a lower specific activity of
      the remaining protein.

PMID- 9610000
TI  - New radiological finding by magnetic resonance imaging examination of the brain
      in Coffin-Lowry syndrome.
AB  - We used magnetic resonance imaging (MRI) to examine the brain of a typical Coffin
      Lowry syndrome (CLS) patient. There were many small perivascular focal areas of
      hypointensity in the white matter on T1-weighted images, similar to those found
      in mucopolysaccharidosis or perivascular leukomalacia. However, these changes
      could not seen in another patient we examined. Both patients showed normal
      urinary mucopolysaccharide patterns with chromatographic analysis. The cause of
      the MRI result is not known, but it could have a heterogeneous origin, and this
      result could represent an important indication defining one type of CLS.

PMID- 9610001
TI  - A severe case of Moebius syndrome with calcification on the fourth ventricular
      floor.
AB  - We report the case of a Japanese girl with a severe type of Moebius syndrome. Her
      morphological features were a mask-like face, limitation of horizontal eye
      movements, severe bulbar palsy, multiple and bilateral arthrogryposis including
      the elbow, knee, and ankle joints, and clubfeet. After birth, her general
      condition became worse because of repeated apneic spells and aspiration
      pneumonias due to dysphagia. She finally required tracheotomy. Computed
      tomography (CT) of the brain revealed minute calcifications on the fourth
      ventricle floor; this may have been due to severe damage to the brain stem. It is
      most likely that the various manifestations in our patient were due to
      disturbance of the blood supply to arteries perfusing the brain stem and to some
      other arteries, at a critical stage of fetal development.

PMID- 9610002
TI  - A case of craniofacial dysmorphism, congenital heart defects, coccygeal skin
      folds, generalized skeletal alterations, and hemihypertrophy with linear skin
      hypopigmentation: a new syndrome?
AB  - The case of a Japanese girl with a unique combination of congenital malformations
      is reported. The malformations include craniofacial dysmorphism, congenital heart
      defects, coccygeal skin folds, generalized skeletal alterations, and
      hemihypertrophy with linear skin hypopigmentation that indicated somatic
      mosaicism of a mutated gene or a submicroscopic chromosomal aberration. The
      phenotype in our patient overlapped significantly with, but was not completely
      consistent with, that of ter Haar syndrome, a recently elucidated malformation
      syndrome with an autosomal recessive trait. The present patient may have
      represented a previously undescribed malformation syndrome, or an atypical
      manifestation of ter Haar syndrome due to somatic mosaicism.

PMID- 9610003
TI  - A SacII polymorphism in the human ASCL2 (HASH2) gene region.
AB  - The mouse achaete-scute homolog-2 gene (Ascl2 or Mash2) encodes a transcription
      factor playing a role in the development of the trophoblast. The Ascl2 gene is
      paternally imprinted in the mouse, but whether this applies to its human homolog
      is unknown. In the present study, we found a SacII polymorphism in the possible
      3' untranslated region (UTR) of the gene. It would be very useful to determine
      definitively whether the gene is imprinted, as well as to analyze the allelic
      methylation status of the gene.

PMID- 9610004
TI  - Isolation and mapping of a polymorphic CA repeat sequence at the human
      interleukin 6 locus.
AB  - A polymorphic dinucleotide (CA) sequence was isolated from a genomic clone
      containing the human interleukin 6 (interferon beta-2) gene and was mapped to
      7p21. This polymorphism will be useful in the genetic study of disorders
      affecting the inflammation process, calcium metabolism, and hematologic
      malignancies.

PMID- 9610005
TI  - Isolation and radiation hybrid mapping of dinucleotide repeat polymorphism at the
      human estrogen receptor beta locus.
AB  - A gene for a second type of human estrogen receptor, the estrogen receptor beta
      (ESR beta), was recently identified. We isolated a polymorphic dinucleotide CA
      repeat marker from a genomic clone containing the human estrogen receptor beta
      gene. High heterozygosity (0.93) makes this polymorphism a useful marker in the
      genetic study of disorders affecting female endocrine systems; calcium
      metabolism; and breast, uterine, and ovarian cancers.

PMID- 9610006
TI  - Isolation and radiation hybrid mapping of dinucleotide repeat polymorphism at the
      human matrix Gla protein (MGP) locus.
AB  - Matrix Gla protein (MGP) is an 84-residue, vitamin K-dependent protein expressed
      by chondrocytes and vascular smooth muscle cells, and is a potent regulator of
      calcium deposition in cartilage and arterial wall. We isolated a polymorphic
      dinucleotide CA repeat marker from a genomic clone containing the human MGP gene.
      This polymorphism will be useful in genetic studies of arteriosclerosis and
      osteoporosis.

PMID- 9610007
TI  - Improving outcomes through a developmental approach to nipple feeding.

PMID- 9610008
TI  - Six steps to better quality nursing care through political action.

PMID- 9610009
TI  - Don't be left out of the loop: using networks and groupware.

PMID- 9610010
TI  - The Nursing Outcomes Classification.
AB  - The Nursing Outcomes Classification (NOC) is a comprehensive taxonomy of patient
      outcomes influenced by nursing care. Each outcome is stated as a variable concept
      measured on a five-point Likert scale and includes a definition, indicators, and
      references. The classification provides outcomes that can be used across the care
      continuum to assess patient status following nursing interventions. The
      classification has a number of advantages, including being research-based,
      standardized, comprehensive, and flexible for clinical use. It was developed by a
      large research team that included clinical experts and has been subjected to
      testing.

PMID- 9610011
TI  - Nursing Outcomes Classification: implications for nursing information systems and
      the computer-based patient record.
AB  - Quality improvement, measurement, and accountability pervade all health care,
      including the agendas of nursing, other care providers, and consumer groups. One
      new face of quality is unequivocal: data will be more equitably shared among all
      groups for data-based quality judgments. This will emphasize quality more than
      cost with greater involvement of the citizens compared to health care providers,
      payers, and health care product suppliers. Emphasis on quality will allow
      patients to have a voice heard and amplified through the implementation of
      patient-centered outcomes in the computerized patient care record. This article
      describes the implications of the Nursing Outcomes Classification (NOC) for
      nursing information systems and the computer-based patient record.

PMID- 9610012
TI  - Implementation and evaluation of Nursing Interventions Classification and Nursing
      Outcomes Classification in a patient education plan.
AB  - Nursing Interventions Classification (NIC) and Nursing Outcomes Classification
      (NOC) are recognized examples of standardized nursing languages used to describe
      the contribution nursing makes to patient care. Columbus Regional Hospital
      nursing leadership recognized the need to use standardized nursing interventions
      and nursing-sensitive patient outcomes to describe the unique contribution
      nursing makes to patient education. In collaboration with the University of Iowa,
      NIC/NOC languages were implemented in the development of a patient education plan
      for a clinical pathway population.

PMID- 9610013
TI  - Implementing nurse sensitive outcomes into care planning at a long-term care
      facility.
AB  - This article describes one long-term care facility's efforts to implement
      standardized language in the care planning process. Federal regulations for long
      term care mandate the use of a uniform comprehensive assessment tool. Eighteen
      Resident Assessment Protocols (RAPs) are identified for data collection. Computer
      databases were revised for care planning. Appropriate North American Nursing
      Diagnosis Association (NANDA) diagnoses were linked to each RAP. Nursing
      Sensitive Outcomes (NOCs) were linked to each NANDA as goals. Nursing
      Interventions Classifications (NICs) were linked to NANDA diagnosis and NOC
      outcomes as approaches. The databases are illustrated, and frequently used NANDAs
      and NOCs are identified.

PMID- 9610014
TI  - Nursing Outcomes Classification implementation projects across the care
      continuum.
AB  - The health care environment in which nurses deliver care is experiencing constant
      change characterized by decreased lengths of stay in acute care settings,
      increased use of technology, increasing emphasis on computerized patient records
      and care planning options, increasing markets dominated by managed care, and an
      emphasis on outcomes rather than process. These changes dictate that nursing as a
      profession ensures that the work of nursing is visible in this health care
      environment and included in the data used to make health policy decisions. This
      article describes the rich history of a Midwestern hospital's use of standardized
      nursing languages for the last 25 years. Currently this facility is in the
      process of implementing the Nursing Outcomes Classification (NOC). Four projects
      are described that illustrate the ways nurses can use this language with
      diagnoses from the North American Nursing Diagnoses Association (NANDA) and
      interventions from the Nursing Interventions Classification (NIC).

PMID- 9610015
TI  - Implementing the Nursing Outcomes Classification in a clinical information system
      in a tertiary care setting.
AB  - Implementing Nursing-Sensitive Outcomes Classification (NOC) is consistent with
      the goal of the Department of Nursing at this tertiary care center to include the
      Nursing Minimum Data Set in the electronic medical record (EMR). This article
      describes the implementation and evaluation of the NOC in selected patient care
      units where a clinical information system is used in conjunction with
      departmental patient care guidelines. In light of identified limitations, the NOC
      was determined to be useful and comprehensive as measured by the frequency of its
      use, the positive feedback by staff, and the minimal additions identified for the
      classification.

PMID- 9610016
TI  - Integrating Nursing Outcomes Classification in nursing education.
AB  - The importance of standardized language to communicate the contribution of
      nursing to the health of patients is beginning to be recognized and embraced by
      the profession. As we move to make standardized language part of nursing
      practice, it is essential to reach nursing educators who prepare future
      generations of nurses for the practice realities of the next century. The Nursing
      Outcomes Classification (NOC) is a valuable tool in nursing education and needs
      to be integrated into the curriculum at all levels. The current emphasis on
      evidence-based practice demands that graduates have the skills and mechanisms to
      measure the outcomes of nursing care.

PMID- 9610017
TI  - Reflections on a trip to Tibet.

PMID- 9610018
TI  - Academic nursing under scrutiny in the United Kingdom.

PMID- 9610019
TI  - Developing reflective learners--student self-assessment as learning.

PMID- 9610020
TI  - Deconstructing and reconstructing history.

PMID- 9610021
TI  - When the mission is teaching: does nursing faculty practice fit?
AB  - As nursing faculty practice becomes a part of academic life, nursing programs in
      liberal arts colleges, where the primary mission is teaching, must document not
      only that practice is scholarship but also that practice conforms to the teaching
      mission of the institution. Discussions of scholarly practice from the nursing
      literature, as well as from Schon and Boyer, serve to validate that nursing
      faculty practice is scholarship. Attributes of scholarly practice, to be used to
      evaluate nursing practice outcomes, are identified. Finally, the concept of
      "scholarship in support of teaching"--the standard used to evaluate scholarship
      at The College of New Jersey, a medium-sized liberal arts college with a school
      of nursing--is analyzed as a model to document that nursing faculty practice is
      not only scholarship but also supports the teaching mission of the institution.

PMID- 9610022
TI  - Impact of interdisciplinary education in underserved areas: health professions
      collaboration in Tennessee.
AB  - A community-based interdisciplinary health professions education project,
      involving the Colleges of Medicine, Nursing and Public and Allied Health, was
      implemented at the undergraduate level at East Tennessee State University from
      1990 to the present. The outcomes of this project and the extension of the
      project into graduate health profession programs are described. Committed
      leadership, effective communication, and genuine community involvement are
      identified as essential to the success of community-based, interdisciplinary
      health professions training programs.

PMID- 9610023
TI  - The business management preceptorship within the nurse practitioner program.
AB  - Changes in health care reimbursement practices have affected the way in which
      primary health care is provided. To be successful, nurse practitioners must have
      a proficient understanding of basic business functions, including accounting,
      finance, economics, marketing, and reimbursement practices. Yet, many graduates
      of nurse practitioner programs are not adequately prepared to make fundamental
      business decisions. Therefore, it is essential that nurse practitioner faculty
      provide learning experiences on primary practice business. Because the preceptor
      experience is an integral aspect of nurse practitioner education, a business
      preceptorship provides students with pragmatic knowledge of the clinical practice
      within a business framework. The University of Indianapolis School of Nursing
      offers a nurse practitioner business preceptorship. The implementation,
      challenges, and positive outcomes of the course are discussed in this article.

PMID- 9610024
TI  - A framework for advanced practice nursing.
AB  - The empirical and expository literatures about advanced nursing practice have
      lacked a broad, comprehensive, conceptual framework to organize and guide
      substantive work. Such a framework is needed during the development of health
      care policy, educational curricula, role descriptions, and research agendas for
      this arena of practice. The framework proposed in this article represents an
      integrative synthesis of previous work on advanced nursing practice. The proposed
      framework is based on the definition of advanced practice nursing as professional
      health care activities that (1) focus on clinical services rendered at the nurse
      client interface, (2) use a nursing orientation, (3) have a defined but dynamic
      and evolving scope, and (4) are based on competencies that are acquired through
      graduate nursing education. Advanced practice nursing is comprised of activities
      in the domains of advanced clinical practice, health care systems management, and
      professional involvement in broad health care discourse.

PMID- 9610026
TI  - Women's choices: an historical perspective of nursing as a career choice.
AB  - Over time there has been debate within nursing regarding its designation as a
      professional career or "skilled craftsperson" job. Although the respectability of
      nursing has always been acknowledged, for some nursing is not considered a high
      status career. This qualitative study sought to identify the reasons why women
      chose to become nurses. Fifteen nurses who had graduated from nursing school
      between 1900 and 1985 were interviewed and asked about their reasons for choosing
      nursing as a career. Various themes emerged as consistent in their choice to
      enter nursing. Paramount was the desire to be of service. The other primary
      motivator was the need for a practical career that was viewed as satisfying,
      flexible, accessible in terms of cost of schooling, always in demand, and
      respectable. When nursing was chosen in the face of family opposition, it was
      viewed as a calling where one could be of service.

PMID- 9610025
TI  - The message of SUPPORT: Study to Understand Prognosis and Preferences for
      Outcomes and Risks of Treatment. Change is long overdue.
AB  - The major findings of the Study to Understand Prognosis and Preferences for
      Outcomes and Risks of Treatment (SUPPORT), a multimillion dollar, multisite
      investigation of the process of dying in American hospitals, were extremely
      disappointing to the medical community. The major conclusion of this intervention
      study was that increased efforts to improve communication about patients'
      preferences for end-of-life care to physicians did not have a significant impact
      on the care that is provided in hospitals. In a commissioned series of papers to
      examine the conclusions of the study, numerous factors were identified as the
      possible reasons for the SUPPORT findings. Among the factors was the role of
      nurses in communicating patients' preferences to physicians. Nurses, however,
      were not participants in the design and conduct of this study nor were they among
      those who were respondents to the conclusions of SUPPORT. In this manuscript, an
      analysis of the report of the SUPPORT study itself and the commentaries
      commissioned by its funding agency are reported. Numerous issues about the
      scientific rigor of SUPPORT, the perceived roles of nurses in end-of-life
      decision making, and the need for interdisciplinary collaboration in health care
      and health care research are presented in an effort to ensure that nurses'
      contributions to the quality of patient care are recognized, acknowledged, and
      valued in the future.

PMID- 9610027
TI  - Genetic testing: implications for professional nursing.
AB  - Scientific information emerging from human genome research has significant
      implications for the practice of professional nursing. Professional nurses assist
      individuals in making decisions about DNA studies, ensure that consent is
      informed before genetic testing, and help clients cope with genetic information
      after test results are known. Nurses with advanced education in genetics identify
      and counsel people who are candidates for DNA testing. Gene identification can
      have beneficial as well as harmful outcomes. Education is needed to prepare
      nurses for new roles regarding genetic testing.

PMID- 9610028
TI  - Immunohistochemical study of p53 overexpression in radiation-induced colon
      cancers.
AB  - The expressions of p53 and proliferating cell nuclear antigen (PCNA) were studied
      immunohistochemically from paraffin sections of 7 cases (9 lesions) of radiation
      induced colon cancer and 42 cases of spontaneous colon cancer. Age distribution
      of radiation-induced and spontaneous colon cancer were 68.1 years (range, 56 to
      77 years) and 67.4 years (range, 31 to 85 years), respectively. Among the
      radiation-induced colon cancers, there were 3 lesions of mucinous carcinoma
      (33%), a much higher than found for spontaneous mucinous cancer.
      Immunohistochemically, p53 protein expression was detected in 7/9 (78%) of
      radiation-induced cancers and in 23/42 (55%) of spontaneous colon cancers. chi 2
      analysis found no significant differences between radiation-induced and
      spontaneous colon cancers in age distribution or p53-positive staining for
      frequency, histopathology, or Dukes' classification. In radiation colitis around
      the cancers including aberrant crypts, spotted p53 staining and abnormal and
      scattered PCNA-positive staining were observed. In histologically normal cells,
      p53 staining was almost absent and PCNA-positive staining was regularly observed
      in the lower half of the crypt. In radiation colitis including aberrant glands,
      cellular proliferation increased and spotted p53 expression was observed. This
      study suggests that radiation colitis and aberrant glands might possess malignant
      potential and deeply associate with carcinogenesis of radiation-induced colon
      cancer.

PMID- 9610029
TI  - Effects of low-dose X-irradiation on the development of the mouse cerebellar
      cortex.
AB  - We labeled proliferating cells of the cerebellum of 6-day-old mice with 5-bromo
      2'-deoxyuridine (BrdU) followed by a single exposure to 0.5, 1 or 2 Gy of X-rays.
      We then studied the effects of low-dose irradiation on the migration and survival
      of granule neurons in the mouse cerebellum. The animals were killed at 4 days, or
      at 2, 4 or 6 weeks after irradiation. Brains were fixed and BrdU-labeled cells in
      the cerebella were immunohistochemically analyzed. BrdU was predominantly
      distributed in the superficial layer of the external granular layer soon after
      injection. Four days after irradiation with 0.5 or 1 Gy, labeled cells were
      mainly seen in the inner granular layer, which was also the case in non
      irradiated mice. However, following 2 Gy irradiation BrdU was found not only in
      the inner granular layer, but also in the Purkinje cell layer. This distribution
      was also seen at 2 and 4-6 weeks after irradiation. In animals irradiated with 1
      Gy 4-6 weeks after irradiation, the proportion of labeled cells present in the
      inner granular layer decreased, while labeled cells in the Purkinje cell layer
      increased. On the other hand, 0.5 Gy irradiation did not change the distribution
      of labeled cells, except that the proportion of labeled cells in the inner
      granular layer decreased at 2 weeks after irradiation. The number of labeled
      cells in the cerebellar cortex per unit area decreased with time and dose. These
      results suggest that 2 Gy irradiation induces a migratory delay, abnormal
      distribution, and cell death of the granule neurons of the mouse cerebellum.

PMID- 9610030
TI  - 3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) sensitizes mammalian cells
      to UV radiation by causing the S-phase arrest, not by inhibiting the repair of
      DNA damage as observed in Escherichia coli.
AB  - 3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) is known to be a mutagen
      and carcinogen isolated from the charred parts of cooked foods. We found
      previously that Trp-P-1 enhanced UV-induced lethality and mutation frequency in
      Escherichia coli by inhibiting the repair of UV-induced DNA damage. In the
      present study, we investigated whether Trp-P-1 also potentiated UV-induced
      lethality by inhibiting the repair of UV-induced DNA damage in cultured mammalian
      cells. As a result, Trp-P-1 enhanced UV-induced lethality in a concentration
      dependent manner in human and Chinese hamster cells. However, Trp-P-1 was unable
      to inhibit the repair of the two major photolesions (cyclobutane pyrimidine
      dimers and (6-4)photoproducts) from the genomic DNA, as determined using
      monoclonal antibodies specific for each type of lesion. On the other hand, Trp-P
      1, with or without UV irradiation, efficiently suppressed DNA synthesis and
      arrested cells in S phase in concentration- and time-dependent manners, as
      measured by pulse-labelling with 3H-thymidine and flow cytometry. Thus, the
      present results suggest that Trp-P-1 potentiates UV-induced lethality in cultured
      mammalian cells by causing the S-phase arrest, not by inhibiting the repair of UV
      induced DNA damage as observed in Escherichia coli.

PMID- 9610031
TI  - Telomerase activity, telomere length, and chromosome aberrations in the extension
      of life span of human embryo cells induced by low-dose X-rays.
AB  - We examined whether the shortening of telomere structure is related to in vitro
      cellular aging after multiple low-dose irradiation. We used three strains of HE
      cells (HE23, HE31, and HE40) exhibiting different levels of telomerase activity
      and irradiated these cells twice a week with a dose of 2 cGy or 4 cGy of X-rays
      until they senesced. The cells were in total exposed to doses of 52-208 cGy of X
      rays. Only the HE31 cells, which had no telomerase activity, experienced an
      increase in the number of cell divisions, reaching a maximum of 120-124% of the
      non-irradiated controls. However, in two strains which did exhibit telomerase
      activity in an early passage in culture, no extension of cell life span was
      found. Telomerase-positive cells completely lost all telomerase activity when the
      cells were subcultured several times without irradiation. In the HE31 cells where
      the life span was extended, the ratio of cell having a long telomere was higher
      than those of the other two cells (HE23 and HE40). Cytogenetic analysis revealed
      that the life span extension due to multiple low-dose irradiation which was
      observed in HE31 cells did not correlate with specific chromosome alterations.
      Our results suggest that the telomerase activity remaining in the cells at an
      early passage does not correlate with the extension of life span in vitro by X
      irradiation. The factor other than telomerase activity may play an important role
      in the regulation of telomere length and the extension of life span.

PMID- 9610032
TI  - Mutant frequencies in lacZ transgenic mice following the internal irradiation
      from 89Sr or the external gamma-ray irradiation.
AB  - Mutagenesis assays using transgenic mice have been recently developed and applied
      to the studies on the mutagenesis. The present study was undertaken to clarify
      whether the mutagenesis assay with transgenic mice could detect the mutations
      induced by the internal beta-ray irradiation from 89Sr or the external gamma-ray
      irradiation. The transgenic mice used were Muta mouse strain, which carries 80
      copies of the bacterial lacZ gene per cell as a target of mutagenesis. Female
      animals were given intraperitoneal injections of ethylnitrosourea (50 mg/kg per
      day) for five days, a single intravenous injection of 89Sr (7.4 and 74 MBq/kg),
      or daily irradiation with 1.5 Gy gamma-rays for five days. The liver, spleen, and
      bone marrow were collected 15 days after the treatment with each agent. After the
      genomic DNA was extracted from each tissue, mutation analysis at lacZ locus was
      carried out. The spontaneous lacZ mutant frequencies were 2-4 x 10(-5). The
      frequencies of mutants induced by ethylnitrosourea in the liver, spleen and bone
      marrow were 68, 55, and 11 x 10(-5), respectively. In contrast, the mutant
      frequencies detected after the treatment with gamma-rays were not so high in all
      three tissues as those treated with ethylnitrosourea. The injection of 89Sr at a
      dose of 74 MBq/kg induced mutation at significantly higher frequencies in the
      bone marrow, but not in the liver and spleen. The results clearly showed that the
      mutation assay system used here could detect mutagenic effects of the local
      irradiation from 89Sr, but was relatively insensitive to the beta- and gamma-ray
      irradiation compared with the chemical mutagens such as ethylnitrosourea.

PMID- 9610033
TI  - Differential dose responses of pulmonary tumor types in the rat after inhalation
      of plutonium dioxide aerosols.
AB  - Dose responses were compared among primary lung tumors and their histological
      types induced by a single inhalation exposure of female Wistar strain rats to
      submicron-size and polydispersed aerosols of plutonium dioxide (239PuO2). While
      the primary lung tumors were found only in 2.3% of the unexposed control animals,
      the frequency of all the primary lung tumors in the exposed animals was 44% at
      the mean lung dose of 0.71 Gy, and increased sharply at the doses of 1.5 Gy or
      more, reaching the maximum of 97% at 5.4 Gy, and the dose responses around at 1.0
      Gy were different between benign and malignant lung tumors. Almost all the
      pulmonary tumors in the exposed animals were classified into epithelial types
      such as adenomas, adenocarcinomas, adenosquamous carcinomas, and squamous cell
      carcinomas. The dose responses were different between these tumor types as shown
      by the peak incidence of adenomas at 0.71 Gy, adenocarcinomas at 2.9 Gy,
      adenosquamous and squamous cell carcinomas at 5.4-8.5 Gy, respectively. As the
      magnitudes of neoplastic lesions in pulmonary carcinomas were expressed by
      histological scores, metaplasias and adenomatous lesions most frequently appeared
      at doses of 1.5 Gy, while the appearance and increase of carcinomatous lesions
      differed in the dose ranges as shown by the peak incidence of adenocarcinomatous
      lesions at 2.9 Gy, and adenosquamous or squamous lesions at 5.4-6.6 Gy. These
      results indicate a differential dose response of pulmonary carcinogenesis in
      which metaplasias and benign adenomas were induced at lower doses (< 1.0 Gy),
      whereas malignant carcinomas were induced at relatively higher doses (> 1.5 Gy).
      Together with the increase of carcinomatous lesions at higher doses, the
      intranuclear p53 protein accumulation was detectable, but only in a few
      percentages of malignant carcinomas.

PMID- 9610034
TI  - An UVB-carcinogenesis model with KSN nude mice.
AB  - We established and characterized a systematic ultraviolet light-induced
      carcinogenesis model using KSN nude mice. We prepared five groups of KSN mice and
      exposed them six times a week to five levels of daily ultraviolet B (UVB) doses;
      1340, 670, 320, 160 and 0 J/m2/day. In 670, 320 and 160 J/m2/day, the latency
      period tended to become shorter in proportion to the daily doses and prevalence
      data fitted well to log-normal distribution. In the log-log plot of days till 50%
      prevalence versus daily dose, we saw a linear relationship for 1 mm tumor
      diameter. From this analysis, we determined that days necessary to reach 50%
      prevalence is in proportion to the -0.49 power of daily dose. The average number
      of tumors per survivor correlated with prevalence data. Direct measured rates of
      tumor growth were independent of daily UVB-dose. Therefore we speculated that UV
      irradiation did not affect tumor growth after its appearance. Most UVB-induced
      tumors were squamous cell carcinoma, the rest were spindle cell carcinoma,
      papilloma and mixed type. We concluded that our experimental data with nude mice
      was in accordance with data with hairless mice in nature.

PMID- 9610035
TI  - Hypertension and public health.

PMID- 9610036
TI  - Hypertension and the eye: applications of the Sixth Report of the Joint National
      Committee on Prevention, Detection, Evaluation, and Treatment of High Blood
      Pressure.
AB  - BACKGROUND: High blood pressure is a major risk factor for coronary artery
      disease, kidney disease, and stroke. More people are aware of treating and
      controlling their blood pressure, but overall control rates are low and the
      incidence of hypertension-related morbidity and mortality remains high. METHODS:
      The National Heart, Lung, and Blood Institute released The Sixth Report of the
      Joint National Committee on Prevention, Detection, Evaluation, and Treatment of
      High Blood Pressure (JNC VI) as the most recent national guideline to
      hypertension control for primary care clinicians. RESULTS: JNC VI identifies 10
      hypertension-related public health challenges: (1) prevent the rise of blood
      pressure; (2) decrease prevalence of hypertension; (3) increase awareness and
      detection of hypertension; (4) improve control of hypertension; (5) reduce
      cardiovascular risks; (6) increase recognition of importance of isolated systolic
      hypertension; (7) improve recognition of importance of high-normal blood
      pressure; (8) reduce ethnic, socioeconomic, and regional variations; (9) improve
      treatment; and (10) enhance community programs. CONCLUSIONS: The eye is a target
      organ and retinopathy is a frequent complication--as well as a prognostic
      indicator--of sustained hypertension. As part of a multidisciplinary team
      approach, the optometrist assumes a significant role in the prevention,
      detection, evaluation, and treatment of high blood pressure and its associated
      morbidities.

PMID- 9610038
TI  - Armaignac's 1906 paper on the recording of visual acuity and the progression of
      letter sizes on visual acuity charts.
AB  - BACKGROUND: Henry Armaignac, a French ophthalmologist in the early twentieth
      century, criticized the Monoyer optometric scale, which was used to measure
      visual acuity. METHODS: This article discusses the "optometric scale" for visual
      acuity letter sizes proposed by Armaignac in a 1906 publication. CONCLUSION:
      Armaignac pointed out the flaws of the Monoyer visual acuity chart commonly used
      in France at the time and suggested an improvement in the progression of letter
      sizes on the chart.

PMID- 9610037
TI  - Acute vision loss resulting from complications of ethanol abuse.
AB  - BACKGROUND: Alcoholism affects about 10% of men and 3% to 5% of women in their
      lifetime. It is a primary chronic disease with genetic, psychosocial, and
      environmental factors that influence its development and manifestations. METHODS:
      A 47-year-old alcoholic male manifested mild nutritional optic atrophy, chronic
      anemia, pancreatitis, and previous gastrojejunostomy and pancreaticojejunostomy.
      After an acute episode of hypovolemic blood loss from peptic ulceration, there
      was increased bi-temporal optic nerve head pallor with permanent vision loss,
      central scotoma, and an acquired red-green color vision defect. RESULTS: The
      genetic, psychosocial, and systemic effects of ethanol abuse--including anemia,
      cardiomyopathy, gastric/duodenal ulceration, pancreatitis, and neurologic
      deficits--are reviewed. Appropriate treatment and management of ocular
      manifestations and complications from alcoholism are discussed. Prophylactic
      topical therapy may be indicated to restore the balance between intraocular
      tension and optic nerve head perfusion in an attempt to prevent further axonal
      loss. CONCLUSION: Alcohol-induced nutritional optic neuropathy should not be
      viewed as an isolated ocular entity, but rather as a potentially treatable
      neurologic problem. An interdisciplinary approach is essential optimal in the
      management of the alcoholic patient.

PMID- 9610039
TI  - A yearly summary of quality assessment and improvement in the optometric
      pediatric clinics of the SUNY College of Optometry.
AB  - BACKGROUND: Each clinic within the University Optometric Center (UOC) of the
      State University of New York (SUNY) College of Optometry develops a Quality
      Management (QM) Plan for each calendar year. The vehicle for implementation is a
      Quality Assessment and Improvement (QA&I) committee. The clinical adherence to
      the objectives are reviewed each year. The following article is a review of the
      QA&I reports of the Pediatric Vision Clinics within the College for the year
      1996. METHODS: Clinical records were concurrently and retrospectively reviewed
      for completeness and appropriateness of care. One hundred percent of the records
      were concurrently reviewed, and 10% of each doctors' total records were
      retrospectively reviewed. In addition, records with specific diagnoses--chosen as
      clinical indicators--were reviewed for a specified period of time. RESULTS:
      Patient satisfaction exceeded predetermined threshold values. On general review,
      the clinical faculty performed at a 95% efficiency level. The pediatric
      population yielded only minimal major pathologies. In our strabismic sample,
      patients with esotropia exceeded those with exotropia (61% vs. 39%). Strabismic
      amblyopes were more prevalent than refractive amblyopes (80% vs. 20%). Preschool
      vision therapy appeared to be successful in most cases. CONCLUSION: Quality
      assessment and improvement is an ongoing process that can provide an overview of
      case management and type. The process serves to monitor quality of care, provide
      a modality for improvement, enhance outcomes, and guide future QM plans.

PMID- 9610040
TI  - Retinal manifestations of idiopathic myelofibrosis, a hematologic disorder.
AB  - BACKGROUND: Idiopathic myelofibrosis (IMF) is a bone marrow and hematologic
      disorder. Retinal and systemic manifestations are observed and result from
      inefficient blood cell production and blood cell irregularities. CASE REPORT: A
      review of IMF as a disease process is presented by way of case report. A 70-year
      old woman came to us with specific systemic symptoms. Further ocular
      investigation revealed bilateral retinal hemorrhages. The hemorrhages were
      consistent with the results of subsequently ordered blood tests. An understanding
      of the underlying systemic condition and recognition of the retinal
      manifestations of IMF aid in the diagnosis. Recognizing differential diagnoses is
      important as well because IMF produces retinal findings similar to other blood
      disorders with comparable blood counts and morphologies. There are certain
      systemic signs the optometrist may look for to assist in the recognition of IMF
      as opposed to the other diseases. CONCLUSION: This is an important disease
      process to recognize, since the systemic and retinal manifestations are within
      optometry's scope to co-manage.

PMID- 9610041
TI  - A brief history of optometry in Israel, 1937 to 1997.

PMID- 9610042
TI  - Spectacle/loupe telescope.

PMID- 9610043
TI  - Two automated perimeters.

PMID- 9610044
TI  - Guidelines for evaluation and management of five common podopediatric conditions.
AB  - Practice guidelines for five of the most common podopediatric deformities are
      presented. In establishing these diagnosis and management guidelines, the authors
      have reviewed an extensive body of literature and considered their experience as
      clinicians in one of the busiest settings for the evaluation and treatment of
      disorders of children's feet. No attempt has been made to be encyclopedic;
      rather, the authors emphasize practical visual descriptors and the rationale for
      treatment to demonstrate the value of early intervention in moderate-to-severe
      orthopedic pathology of the foot and leg.

PMID- 9610045
TI  - Congenital talonavicular coalition. Review of the literature, case report, and
      orthotic management.
AB  - Talonavicular coalition is a rare entity and is often discovered as a secondary
      radiographic finding. Today, orthoses are as varied as the patients for whom they
      are prescribed; however, in cases of symptomatic talonavicular fusion, the use of
      a shallow U-shaped dispersion within the high medial flange of an orthosis can
      prove beneficial to the pediatric patient. This article encourages podiatric
      physicians to return to utilizing basic diagnostic tools (gait analysis,
      biomechanical examination, and radiographs) to detect and treat talonavicular
      coalition, a significant but rare anomaly of the foot.

PMID- 9610046
TI  - Cutaneous larva migrans infection in the pediatric foot. A review and two case
      reports.
AB  - Cutaneous larva migrans is the result of infestation of human skin by helminth
      larvae, which burrow through the epidermis. This route of infestation makes the
      foot a typical site for origination of this infection. Children, who frequently
      play barefoot in locations where the most common of the helminth larvae, the dog
      and cat hookworms, are endemic, are at particular risk for this disorder. This
      article reviews the differential diagnosis of cutaneous larva migrans and current
      concepts in management. Two cases of related children who presented to their
      pediatricians with this condition are reported.

PMID- 9610047
TI  - Pediatric resources on the Internet.
AB  - This article introduces the podiatric physician interested in pediatrics to the
      resources available on the Internet. It surveys search engines, gateway sites on
      the World Wide Web leading to a wealth of pediatric information and services, and
      features such as electronic mail, news-groups, and Gopher sites. Examples
      illustrate how such resources can be helpful to the practicing podiatrist.

PMID- 9610048
TI  - Foot problems associated with older patients. A focused podogeriatric study.
AB  - The authors report on a 3-year prospective program that included foot-health
      education and an initial assessment of foot problems in an older population. The
      program represents a cooperative effort by the Philadelphia Corporation for Aging
      and the Pennsylvania College of Podiatric Medicine to enhance the quality of life
      of older citizens. The results show that foot problems are prevalent among older
      patients. The program also refined a protocol that can be applied in other
      settings.

PMID- 9610049
TI  - Foot-care awareness. A survey of persons aged 65 years and older.
AB  - The authors conducted a mail survey that examined foot problems, rates of
      utilization of foot-health services, and the perception of foot problems as
      medical conditions in a sample of people aged 65 years and older who lived
      independently. Although 71% of the 128 respondents reported suffering from foot
      problems, only 39% had consulted medical personnel about their feet, and only 26%
      identified their foot pathologies as medical conditions. More female than male
      respondents experienced foot problems and had visited medical personnel about
      their feet. Increased education of older individuals about their foot-care
      requirements, as well as increased access to podiatric medical services, is
      recommended.

PMID- 9610050
TI  - Neuropathy associated with prostate cancer.

PMID- 9610051
TI  - Central pain syndrome with manifestations in the foot.

PMID- 9610052
TI  - Alternative techniques for the clinical assessment of foot pronation.

PMID- 9610053
TI  - Sex difference in the mortality trends of acute myocardial infarction in Taiwan,
      1974 to 1993.
AB  - The mortality patterns of coronary heart disease (CHD) vary among countries.
      Although the mortality rates from this disease are decreasing in the majority of
      developed nations, most developing countries are experiencing upward trends,
      especially among men. The mortality trends of acute myocardial infarction (AMI)
      in Taiwan have not been reported. The purpose of this study was to investigate
      the effects of age, chronicle period, and birth cohort on the AMI mortality rates
      using computerized vital statistics data from 1974 through 1993. Compared with
      the age-adjusted AMI mortality rates in 1974, the mortality rates in 1993 were
      2.4 times higher for men and 2.2 times higher for women. When the log-linear
      Poisson model was used to assess age, birth cohort, and chronicle period
      simultaneously, women had no elevated relative risk of dying from AMI in
      different periods. The relative risk of dying from AMI increased 2.5 times for
      men in the 1955-1959 birth cohort compared with those in the 1890-1894 birth
      cohort, while the relative risk for females declined by 3.7 times for the
      corresponding birth cohorts. Based on birth cohort, the trends in mortality
      differ substantially between sexes in Taiwan. These results may help to generate
      hypotheses regarding the possible factors, prevention, and control of mortality
      from AMI in Taiwan.

PMID- 9610054
TI  - Normal standards for cardiopulmonary responses to exercise using a cycle
      ergometer test.
AB  - The purpose of the study was to establish standards for cardiopulmonary responses
      to exercise in healthy Chinese subjects in Taiwan. One hundred and five sedentary
      healthy subjects, 55 men and 50 women aged between 20 and 75 years, were tested.
      They pedalled a cycle ergometer with the work rate increased by 10 W every minute
      until they were exhausted. Expiratory gas volume, oxygen concentration, carbon
      dioxide concentration, and heart rate were measured during the exercise test.
      Work rate (WRmax), oxygen consumption (VO2max), oxygen consumption divided by
      body weight (VO2max/BW), heart rate (HRmax), and ventilation (VEmax) at maximal
      exercise, and oxygen consumption at anaerobic threshold (VO2AT) were determined.
      These parameters were regressed by age (A, in year), height (H, in cm), body
      weight (G, in kg), and gender (S, 0 = women, and 1 = men), and the following
      predictive equations were obtained: 1) WRmax (W) = -1.2 A + 1.1 H + 0.7 G + 28 S 
      56, R = 0.90; 2) VO2max (ml/min) = -20 A + 9.5 H + 16 G + 461 S - 237, R = 0.90;
      (3) VO2max/BW (ml/kg/min) = -0.31 A + 0.14 H - 0.14 G - 7.2 S + 22, R = 0.87; 4)
      HRmax (beat/min) = -0.81 A + 209, R = 0.61; 5) VEmax (L/min) = -0.74 A - 0.04 H +
      0.93 G + 22.2 S + 42, R = 0.83; 6) VO2AT (ml/min) = -9.5 A + 3.5 H + 9.4 G + 140
      S - 122, R = 0.79. Our results provide normal standards for cardiopulmonary
      responses to exercise during cycle ergometer testing in Taiwan.

PMID- 9610055
TI  - Tissue plasminogen activator reduces intraperitoneal adhesion after intestinal
      resection in rats.
AB  - We investigated whether tissue plasminogen activator (tPA), a plasma serine
      protease that catalyzes the initial and rate-limiting step in fibrinolysis,
      inhibits postoperative intraperitoneal adhesion formation in rats. Male Wistar
      rats weighing 200 to 250 g underwent laparotomy with a 15-cm intestinal resection
      and reanastomosis; the intestinal serosa was scratched to induce adhesion
      formation. The rats were divided into three groups: the control group received no
      medication; the normal saline group received peritoneal irrigation with 6 mL
      normal saline intraoperatively; and the tPA group received peritoneal irrigation
      with 6 mL tPA solution (5 mg/L) intraoperatively. The rats were killed 7 or 14
      days later. The scores (severity of adhesion, 0-3 point scale), strength, and
      extent of fibrous bands were recorded on the day the rats were killed. Wound
      strength was measured using an Instron tensionmeter immediately after the rats
      were killed. The concentrations of plasma tPA and plasminogen activator inhibitor
      (PAI)-1 and -2 were measured. The scores and strength of fibrous bands in the tPA
      group were lower than those in the control and saline groups whereas wound
      strength was similar in all groups. The plasma tPA concentration was
      significantly higher and the plasma PAI-1 and PAI-2 concentrations were
      significantly lower in the tPA group than in the control and saline groups on the
      7th and 14th postoperative days. Our findings suggest that tPA can reduce the
      incidence of postoperative intraperitoneal adhesions without impairing wound
      healing.

PMID- 9610056
TI  - Clubfoot deformity in congenital constriction band syndrome: manifestations and
      treatment.
AB  - Clubfoot deformity associated with congenital constriction band syndrome (CCBS)
      has different characteristics than classic idiopathic clubfoot, and is more
      difficult to treat. We describe the manifestations, treatment, and outcomes of
      nine patients treated for 11 CCBS-associated clubfoot deformities between 1980
      and 1993. All but one of these children had an abnormal gestational or neonatal
      history. From an assessment of the correctability of the deformity and the
      associated secondary changes, the clubfoot severities were all classified as
      grade B (intermediate). The constriction bands in eight clubfeet were classified
      as type 0 (5 feet), II (2), or III (1), according to the location and depth of
      the band. Band types in three feet were unclassified because the band release was
      performed at other hospitals. We released the bands before correcting the
      clubfeet in the two patients with type II bands. The five patients with type 0
      bands received casting first but with poor response. All clubfeet were corrected
      surgically; the procedures were posteromedial release in 10 feet, split tibialis
      anterior tendon transfer in five, and lengthening of the Achilles tendon in
      three. At an average follow-up of 3.8 years, seven of the 11 clubfeet were
      classified as having good results and four as fair. Among the six clubfeet with
      constriction bands on the ipsilateral leg, five were classified as having good
      results and one as fair. Two of the five clubfeet without constriction bands on
      the ipsilateral leg had good results and three had fair results. The presence of
      a band did not influence the final outcome of the clubfoot deformity (p > 0.05).
      In the five patients with forefoot varus deformity due to peroneal weakness,
      tibialis anterior tendon transfer successfully corrected the deformity. All the
      clubfeet treated in this series were plantigrade after treatment and had
      satisfactory results.

PMID- 9610057
TI  - Wrist arthrodesis using a slab bone graft from the dorsal radius.
AB  - Arthrodesis is a well-established procedure for the management of wrist
      deformity, instability, and arthritis resulting from various causes. Several
      techniques, with or without internal fixation or heterotopic bone grafting, have
      been described, but no single procedure has gained general acceptance. We present
      our results using a simple and reliable technique that employs a local bone graft
      and light internal fixation. From 1987 to 1996, eight consecutive patients with
      wrist lesions were treated using a modified Gill procedure for arthrodesis. The
      average age of patients was 62 years and the mean follow-up period was 4 years. A
      slab corticocancellous bone graft harvested from the dorsal aspect of the distal
      radius was turned about to cover the fusion mass from the distal radius to the
      third metacarpal bone. Kirschner wires and tension band wires were used to fix
      the wrist and compress the bone graft. A long arm cast was applied for 6 weeks,
      followed by a short arm cast until arthrodesis was achieved. The wrist position
      was well maintained by the tension band wire alone thereafter. Pain relief, grip
      strength, and assessment of daily activities were documented. Solid fusion was
      achieved smoothly in all cases and all patients were satisfied with the results.
      We recommend this simple and reliable technique for wrist arthrodesis.

PMID- 9610058
TI  - Gain of muscle torque at low and high speed after isokinetic knee strengthening
      program in healthy young and older adults.
AB  - Low-speed isokinetic exercise has been recommended to exert a maximal contraction
      and produce greater muscle torque than high-speed exercise in young adults. The
      purpose of this study was to compare the effectiveness of low- and high-speed
      isokinetic exercise programs for increasing muscle torque in young and elderly
      people. Twenty healthy elderly and 20 young subjects participated. The elderly
      subjects were divided into two groups. One group performed high-speed (300
      degrees/s) isokinetic exercise training three times a week for the dominant-side
      knee extensor and low-speed (60 degrees/s) exercise for the non-dominant side for
      6 weeks. The other group was trained using the reverse exercise regime. The
      training program for the young subjects was the same as that for the elderly
      groups. All subjects had their knee extensor torque evaluated with an isokinetic
      test before and at 2-week intervals during the training program. For young and
      elderly groups, both high- and low-speed isokinetic exercise training increased
      extensor torque in low- and high-speed tests. For the young group, low-speed
      exercise effectively improved muscle torque at low and high speeds. The
      improvement in slow muscle torque was significantly greater than that in fast
      muscle torque. For the elderly subjects, high-speed isokinetic exercise produced
      the greatest muscle torque at high speed in the first 2 weeks of training, and
      demonstrated a sharp increase in muscle torque in the final 2 weeks. Low-speed
      exercise frequently caused knee stress and the inability of some elder subjects
      to continue the exercises with maximal effort. Our findings indicate that high
      speed exercise may be more appropriate for the elderly, and low-speed exercise
      may be more appropriate for younger people.

PMID- 9610059
TI  - The impact of a clinical pathway for transurethral resection of the prostate on
      costs and clinical outcomes.
AB  - The purpose of this study was to evaluate the effects of implementing a clinical
      pathway for transurethral resection of the prostate on hospital costs and
      procedures, outcomes, and complications. Consecutive patients who underwent
      transurethral resection of the prostate for benign prostate hyperplasia in our
      hospital before (February-August 1996) and after (October 1996-March 1997)
      implementation of the clinical pathway were included. Statistical analyses
      included Student's t-test to test the impact of the clinical pathway on resource
      consumption and medical care processes, and multiple linear regression to control
      for patient characteristics such as age, severity of disease, and comorbidity.
      The major findings of this study were that implementation of the clinical pathway
      1) decreased resource consumption and controlled medical care expenditure; 2)
      influenced physicians' patterns of practice and decreased the number of
      procedures performed; and 3) did not affect clinical outcomes or complication
      rates. In conclusion, our results support the hypothesis that the clinical
      pathway is an effective medical management tool to contain costs, which does not
      adversely affect quality of care. We suggest health policy makers promote
      clinical pathways in more hospitals to encourage appropriate resource
      consumption.

PMID- 9610060
TI  - A patient with familial Takayasu's arteritis presenting with fever of unknown
      origin.
AB  - Takayasu's arteritis rarely presents with fever of unknown origin. We describe a
      14-year-old girl who was admitted with a 2-month history of fever of unknown
      origin associated with vague pain in her left upper arm. The constitutional
      symptoms responded to a trial of steroid therapy for suspected collagen-vascular
      disease, but flared up when the dose was tapered. An asymmetric radial pulse was
      recognized incidentally during follow-up examination; diagnosis of Takayasu's
      arteritis was confirmed by Duplex ultrasonography and angiography. Takayasu's
      arteritis must be considered when evaluating children with fever of unknown
      origin, especially those with a positive family history. Careful assessment of
      the peripheral vascular system with better interpretation of limb symptoms should
      allow early, appropriate treatment to prevent irreversible vascular damage.

PMID- 9610061
TI  - X-linked recessive bulbospinal neuronopathy: clinical and molecular studies in a
      Taiwanese family.
AB  - We describe clinical, biochemical, and molecular studies on a Taiwanese family
      with X-linked recessive bulbospinal neuronopathy. There were three probands and
      five female carriers among the 23 members examined. The clinical manifestations
      included progressive muscle weakness, diffuse fasciculation, postural tremor,
      muscle cramps, dysarthria, dysphagia, diabetes, and gynecomastia. Phenotypic
      expression varied among the affected subjects. Two carriers also had postural
      tremor and perioral fasciculation. Endocrine tests were normal except for a mild
      increase in serum testosterone and/or growth hormone in one patient and one
      carrier. Type IV hyperlipoproteinemia was observed in two patients, one carrier,
      and one healthy offspring. Molecular genetic studies confirmed elongation of the
      CAG triplet repeat in exon 1 of the gene for the androgen receptor. Sequence
      analysis showed that there were 42 to 43 CAG repeats in the three probands and 42
      to 45 in the five carriers. The mutant allele had a tendency to increase by one
      or two repeats from one generation to the next. The length of CAG repeats at
      which the mutant allele became unstable was shorter in our family than in
      previous reports. The normal allele was also unstable and had a tendency to
      shrink by one of five repeats during transmission. These findings suggest that
      the number of CAG triplet repeats is variable in both the mutant and normal
      alleles.

PMID- 9610062
TI  - Reconstruction of circumferential pharyngeal defect following cancer surgery with
      tubed pectoralis major myocutaneous flap and interdigitating anastomosis.
AB  - Hypopharyngeal cancer has a poor prognosis and the tumor may spread submucosally
      to involve all the pharyngeal mucosa. Reconstruction of circumferential defects
      after resection of hypopharyngeal cancer is a challenge. We describe our results
      using a tubed fan-shaped pectoralis major myocutaneous flap and distal
      interdigitating anastomosis to reconstruct a circumferential pharyngeal defect
      following surgical resection in six patients with advanced hypopharyngeal cancer.
      There was no perioperative mortality in this study. Fistula formation occurred in
      three patients and was corrected by secondary closure in two and spontaneous
      healing in one. Oral intake was started 2 weeks to 2 months after surgery. Four
      patients died of distant metastases within 24 months of follow-up and two
      survived without disease. Neither locoregional recurrence nor stenosis occurred.
      Our results show that the tubed fan-shaped pectoralis major myocutaneous flap
      with distal interdigitating anastomosis is a reliable way to reconstruct
      circumferential pharyngeal defects, and is relatively noninvasive.

PMID- 9610063
TI  - Extracorporeal membrane oxygenation in treatment of cardiogenic shock caused by
      acute myocarditis.
AB  - We report a 31-year-old woman with acute myocarditis who was transferred to our
      hospital because of rapidly progressive cardiogenic shock unresponsive to
      infusion of high doses of inotropic agents and intraaortic balloon pump support.
      Upon arrival at our hospital, extracorporeal membrane oxygenation (ECMO) was
      immediately established through a right femoral venoarterial route by
      percutaneous cannulation; the blood flow of ECMO was maintained at around 2,100
      mL/min. Shock-induced rhabdomyolysis complicated with acute renal failure
      occurred. During treatment with ECMO and hemodialysis, the patient gradually
      recovered cardiac and renal function. The patient was maintained on ECMO for 90
      hours then successfully weaned from the machine without major complications. Our
      experience suggests that ECMO can be used for temporary mechanical circulatory
      support in patients with cardiogenic shock due to acute myocarditis.

PMID- 9610064
TI  - Penetrating chest injury: who warrants aggressive treatment?
AB  - To determine the degree of severity in penetrating chest injuries that predicts
      survival, we conducted a logistic regression analysis. All patients suffering
      penetrating chest injuries (n = 310) admitted to an urban level I teaching
      hospital in the USA between January 1993 and December 1994 were evaluated. The
      Injury Severity Score (ISS), Glasgow Coma Scale (GCS), Trauma Score (TS), and
      Revised Trauma Score were used to compare injury survivors with nonsurvivors. We
      used the trauma scores to create a logit to predict the outcome among 160
      patients in 1993 and tested the validity of this logit in another 150 patients in
      1994. With death = 0, survival = 1, the equation lnPd/Ps = b0 + b1 ISS + b2 GCS +
      b3 TS was obtained from logistic regression, where b0 was the constant of the
      equation and b1, b2, and b3 were the coefficients of ISS, GCS, and TS,
      respectively. A logit score greater than 0.5 was found to be predictive of death
      with a sensitivity of 80.0%, a specificity of 97.5%, and an accuracy of 94.0%.
      Aggressive resuscitation should be aimed at patients with a logit score greater
      than 0.5 to reduce mortality. This knowledge may aid in the management of
      patients with severe chest injuries.

PMID- 9610065
TI  - ECG of the month. Cool dude! Hypothermia.

PMID- 9610066
TI  - Pediatric airway foreign bodies.
AB  - Foreign body aspiration (FBA) is a leading cause of accidental death in children
      less than one year old and is the cause of death in 7% of children less than
      four. Food items, especially peanuts, are the most common items aspirated in
      infants and toddlers, whereas older children are more likely to aspirate non-food
      items such as pen caps, pins, and paper clips. A high degree of suspicion is
      required to diagnose FBA. A history of a witnessed choking episode is most
      important in early diagnosis. An asymptomatic period is common after aspiration
      and contributes to a delay in diagnosis of greater than one week in 12% to 26% of
      patients. This delay in diagnosis causes increased morbidity from bronchial
      inflammation, obstruction, and pneumonia which is resistant to treatment. Prompt
      endoscopic removal of the foreign body with an open rigid bronchoscope under
      general anesthesia is the mainstay of therapy.

PMID- 9610067
TI  - Radiology case of the month. Painless enlargement of the jaw. Giant cystic
      ameloblastoma of the left mandible.

PMID- 9610068
TI  - The Journal 100 & 150 years ago. Devils, doctors, and deities. 19th century
      surgeons of Louisiana.

PMID- 9610069
TI  - The Louisiana Cancer and Lung Trust Fund Board.

PMID- 9610070
TI  - Cancer incidence in the industrial corridor: an update.
AB  - Because of the high density of industries along the Lower Mississippi River,
      there is a concern about adverse impact on health, including cancer, among
      residents in these parishes. This study provides an update of cancer incidence in
      the Industrial Corridor for the period 1989-93. Age-adjusted cancer incidence
      rates were calculated for the seven-parish study area from Baton Rouge down to,
      but not including, New Orleans. Rates were also computed for the entire state of
      Louisiana and for the combined Surveillance, Epidemiology and End Results (SEER)
      program. Cancer incidence rates for the Industrial Corridor are either similar
      to, or lower than, the combined SEER rates for most of the common cancers as well
      as for rare tumors. The only two exceptions are lung cancer in white males and
      kidney cancer in white females that are significantly elevated when compared to
      the SEER averages. Significantly lower rates are found among white males for
      cancers of kidney, brain, and nervous system, and melanoma; among black males,
      cancers of all sites combined, oral cavity, stomach, rectum, and prostate,
      Hodgkin's disease, and non-Hodgkin's lymphoma; among white females, cancers of
      all sites combined, cervix, uterine corpus, ovary, bladder, and melanoma; and
      among black females, cancers of all sites combined, oral cavity, lung, breast,
      ovary, and melanoma. The persistent excess of lung cancer has led to the
      development of a multi-agency project to evaluate the impact of potential
      environmental exposures, genetic susceptibility, and their interactions on lung
      cancer risk. The findings also confirm the urgent need to include and strengthen
      tobacco prevention and cessation programs in our cancer control activities.

PMID- 9610071
TI  - Gene therapy for malignant mesothelioma: a novel approach for an incurable cancer
      with increased incidence in Louisiana.
AB  - Malignant mesothelioma (MM) is a tumor of the pleura for which there is no
      satisfactory treatment. It is an almost universally fatal disease, regardless of
      the stage of the tumor at the time of diagnosis. Current treatment modalities
      include surgery, chemotherapy, and radiation therapy, although in some series
      none of these modalities is superior to no treatment at all. Because of the
      dismal prognosis for patients with MM, new modes of treatment are desperately
      needed. A promising area of research into the treatment of various malignancies
      is gene therapy. Recent studies have demonstrated the utility of exposing tumor
      cells to cells transduced to express the Herpes simplex virus gene for thymidine
      kinase (HSV-TK). By virtue of their expression of HSV-TK, the transduced cells
      are rendered susceptible to the antiviral drug, ganciclovir (GCV). Nearby
      untransduced tumor cells are killed by a so-called bystander effect. We are
      describing a Phase I clinical gene therapy trial for MM, which we are presently
      conducting at the Louisiana State University Medical Center of New Orleans. The
      purpose is to study the safety and to determine the maximal tolerated dose of an
      HSV-TK-transduced ovarian cancer cell line (PA1-STK cells) that is infused into
      the pleural cavities of patients. This infusion is followed by systemic
      administration of GCV. The hope is that administration of GCV will result in
      killing of both the transduced ovarian cancer cells as well as the nearby
      malignant cells.

PMID- 9610072
TI  - p53 molecule as a prognostic marker in human malignancies.
AB  - The tumor suppressor gene, p53, is the most commonly mutated gene associated with
      cancer. Mutation of p53 plays a critical role in the multiple stages of
      carcinogenesis. The functional inactivation of p53 by missense mutations has been
      described in various cancers and the majority of these mutations occur in exons 5
      through 9 of the p53 gene. Mutations leading to the overexpression of p53 have
      been found to affect the patient survival outcome in several human malignancies.
      Our experience with more than 200 samples of breast and prostate carcinoma is
      presented. Our results strongly suggest that the type and location of the p53
      mutations within the molecule may affect and dictate the outcome of cancer.

PMID- 9610073
TI  - Lung-specific expression in mice of a dominant negative mutant form of the p53
      tumor suppressor protein.
AB  - Lung cancer is the most frequent cause of cancer deaths in the United States. A
      strong correlation exists between mutations in the gene encoding the p53 tumor
      suppressor protein and lung malignancies. Our goal is to prepare a transgenic
      mouse model with disrupted p53 function in the epithelial cells of the peripheral
      lung. To achieve this goal, a "dominant negative" mutant form of p53 was
      expressed from the human surfactant protein C (SPC) promoter. The dominant
      negative p53 expressed from the SPC promoter will antagonize wild-type p53
      functions in alveolar type II pneumocytes and some bronchiolar cells of the
      transgenic animals and thereby promote development of carcinoma of the lung. This
      animal model should prove useful to the study of lung carcinogenesis and to the
      identification of agents that contribute to neoplastic conversion in the lung.

PMID- 9610074
TI  - Role of technetium-99m sestamibi myocardial imaging in the emergency department
      evaluation of chest pain.
AB  - The use of technetium-99m sestamibi myocardial imaging is rapidly becoming a
      state of the art methodology for the emergency department evaluation of patients
      with chest pain. The following case report represents the first emergency
      department sestamibi scan ordered at the University of Mississippi Medical Center
      and is used to discuss the logistics and indications for such tests. A general
      guideline for ordering sestamibi scans has been developed for use in the
      emergency department.

PMID- 9610075
TI  - Oral magnesium for tocolysis: a comparison of magnesium gluconate and enteric
      coated magnesium chloride.
AB  - PURPOSE: Following parenteral magnesium tocolysis for patients in preterm labor.
      The choice of oral tocolytic medications is controversial. METHODS: Over a six
      month period, 47 patients who were inpreterm labor were randomized after
      parenteral magnesium tocolysis to receive magnesium gluconate ([Mg-g] 648 mg
      elemental magnesium/day) or magnesium chloride ([Mg-c] 640 mg elemental
      magnesium/ day). A serum magnesium was obtained 24 hours after the initiation of
      oral therapy. RESULTS: In the 25 patients were treated with Mg-g and 22 with Mg-c
      there were no differences in patient demographics, initial cervical dilatation
      hours on parenteral magnesium sulfate, recurrent contractions, or side effects
      between the two groups. The cost was also similar (Mg-c, $1.40/d; Mg-g, $2.11/d).
      The serum magnesium levels were higher in the Mg-c group (1.80 +/- 0.28 mg/dl)
      compared to the Mg-g group (1.63 +/- 0.30 mg/dl) but the difference was not
      significant. CONCLUSION: These two preparations of magnesium are similar in their
      effects on uterine activity and serum levels when used at these dosages.

PMID- 9610076
TI  - Isoenzymes in parasitic disease.

PMID- 9610077
TI  - Methotrexate in rheumatoid arthritis: a 2 year experience at a university
      hospital in Pakistan.
AB  - In this study we report our two years experience of methotrexate (MTX) in the
      management of rheumatoid arthritis (RA) at the Aga Khan University Hospital,
      Karachi. We studied the clinical course of 124 RA patients. The mean age was 44
      +/- 11 years (range 19-72) and mean duration of RA was 5 +/- 4 years (range 0.3
      25). Female to male ratio was 10:2.4 (100F:24M). All of them were diagnosed
      according to the criteria set by American Rheumatism Association. The mean value
      of ESR was 60 +/- 30 (Range 3-128). Fifty one percent had severe disease (> 10
      joints involved and evidence of erosions and deformities). Twenty-one patients
      had extra-articular manifestations. None of them had received MTX previously.
      Their kidney and liver functions were assessed to be normal. Patients were
      divided into two groups. One group (n = 92) received MTX (7.5-10 mg/week) as
      initial treatment, while the other group (n = 32) was given other disease
      modifying anti-rheumatic drugs (penicillamine, salazopyrin, gold, or chloroquine)
      followed by MTX. Assessment of the treatment outcome and development of any
      adverse reactions was carried out at 3-month interval over an average period of 1
      year. Assessment of the treatment outcome in the group which received MTX as
      initial drug revealed the response to be excellent in 13%, good in 70%, fair in
      11% and variable in 4%. In the group which received MTX as second-line of
      therapy, 59% of the patients had the response from good to excellent, while 25%
      of the patients exhibited poor to fair response. Regarding side-effects of MTX
      treatment, 57% exhibited none, while 35% had nausea and vomiting. Alopecia was
      the next common toxicity in these patients. Two individuals had abnormal liver
      function tests (value twice more than normal), while one developed lung fibrosis.
      MTX despite its adverse effects in some of the patients is still an effective,
      well tolerated and inexpensive disease modifying drug in RA.

PMID- 9610078
TI  - Diagnostic evaluation of fine needle aspiration cytology in the management of
      palpable breast lesions.
AB  - A total of 113 fine needle aspirates of the breast masses were evaluated in which
      the subsequent biopsy or mastectomy specimen were also available for histological
      examination. The age ranged from 16 to 80 years with a mean of 42 years. In
      benign conditions the mean age was 34.7 years while in malignant cases it was 48
      years. The cytological diagnoses were compared with the histological results
      which revealed that the specificity and sensitivity of fine needle aspiration
      cytology in the palpable breast lesions was 86.1% and 89.2% respectively with a
      positive predictive value of 93% and efficiency of 88.2%. Similar statistics from
      other series in which the cytological results of breast lesions were compared
      with histological results, revealed almost same results which suggest that fine
      needle aspiration cytology is an effective and accurate technique for the
      diagnosis and management of palpable breast lumps.

PMID- 9610079
TI  - Pemphigus in Pakistan, a study of 108 cases [corrected].
AB  - Pemphigus has an average age of onset in the fifth and sixth decades of life,
      with a mean age of onset of about 50 to 60 years. In this study of 108 patients
      conducted in Karachi, Pakistan, 82 had pemphigus vulgaris, 24 pemphigus foliaceus
      and 2 pemphigus vegetans. Other types of pemphigus were not seen. Seventy cases
      were under 41 years with the mean age at the time of diagnosis being 33.8 years,
      which is considerably low compared to that mentioned in standard western
      literature. Considerable variation in the age incidence of the disease exists in
      different geographic locations.

PMID- 9610080
TI  - Magnitude of lipoprotein (a) in diabetes mellitus.
AB  - One hundred and three patients, 76 with diabetes mellitus alone (48- Non-Insulin
      dependent diabetes and 28 Insulin dependent diabetes) and 27 diabetics having
      coronary heart disease (CHD) and 27 normal control subjects were included in this
      study. All the 27 diabetics with CHD were Non-Insulin dependent. The patients and
      the controls were investigated for serum Lp (a), triglycerides, cholesterol, VLDL
      C, LDL-C, HDL-C, apo A1 and apo B. The objective was to assess and compare the
      level of lipoproteins, especially the lipoprotein (a), in diabetic and non
      diabetic subjects and to compare the level of the aforementioned parameters in
      diabetics with and without CHD. The Lp (a) and other lipid parameters were
      significantly raised (P < 0.001) except HDL-C and apo A1 that were significantly
      decreased (P < 0.001) both in diabetic patients with and without CHD, as compared
      to the control group. The diabetics with CHD showed significantly elevated (P <
      0.001) Lp (a) and lipid profile, and significantly low (P < 0.001) HDL-C and apo
      A1 levels as compared to the patients having diabetes alone. No significant
      difference was observed in the levels of the above parameters when NIDDM patients
      were compared with IDDM group. In both NIDDM and IDDM patients significantly low
      (P < 0.001) HDL-C level and significantly high (P < 0.001) Lp (a) level along
      with the aforementioned lipid parameters was observed as compared to control
      group. Elevated levels of Lp (a) and lipid profile in diabetic subjects suggest
      their involvement in atherogenesis and subsequent development of CHD.

PMID- 9610081
TI  - Frequency of gastrointestinal tumours at a teaching hospital in Karachi.
AB  - Malignant gastrointestinal tumours are amongst the commonest tumours exhibiting
      an annual increase globally. There is a change in the morphological site of
      involvement observed over the years. In this study biopsy proven malignant
      gastrointestinal tumours seen at Jinnah Postgraduate Medical Centre, Karachi from
      1961-1992 were analyzed with reference to age, sex, topography and histology. The
      study showed an increase in malignant gastrointestinal tumours over the years,
      from 9% in 1961 to 17% in 1992 with respect to all malignant tumours reported.
      The tumours affected a much younger age in our population, 74% occurring between
      35-64 years of age. Carcinoma oesophagus accounted for 10% of all malignancies
      (48.7% male and 62.4% female gastrointestinal tumours), while gastric carcinoma
      remained unchanged (14% male and 9% female GI tumours). The colorectal carcinoma
      (25.4% of male and 20.1% of female GI tumours) and carcinoma pancreas (1.2% male
      and 1.5% female GI tumours) were less frequently seen. It was observed that
      malignant gastrointestinal tumours have increased significantly over the years in
      our local population as part of international trend and are occurring at a much
      younger age as compared to western population. Carcinoma oesophagus was seen more
      frequently than gastric carcinoma and colorectal carcinoma. A substantially
      higher number tend to be more anaplastic being seen at an advanced stage of
      disease at the time of diagnosis.

PMID- 9610082
TI  - Predictive value of MCV/RBC count ratio to discriminate between iron deficiency
      anaemia and beta thalassaemia trait.
AB  - AIM AND BACKGROUND: Two forms of hypochromic microcytic anaemia i.e. iron
      deficiency and beta-thalassaemia trait are common in our society. This study
      reports the prevalence of iron deficiency anaemia and beta-thalassaemia trait and
      predictive value of MCV/RBC count ratio to discriminate between two. METHODS:
      Venous blood was taken from 299 students of Karachi Medical & Dental College and
      Ziauddin Medical University in Na2 EDTA and analyzed by semi-automated Sysmex K
      1000 haematology analyzer. MCV/RBC count ratio was used to discriminate between
      iron deficiency and beta-thalassaemia trait and > 14% was marked as iron
      deficiency. Hb electrophoresis was used as gold standard test for confirmation.
      Serum iron and TIBC was performed to confirm iron deficiency anaemia. RESULTS:
      Iron deficiency was found in 9% while beta-thalassaemia was seen in 3% students.
      MCV/RBC count ratio showed a positive predictive value of 91%. CONCLUSIONS: In
      areas where iron deficiency anaemia and beta-thalassaemia trait are common,
      MCV/RBC count ratio can be used to screen out beta-thalassaemia trait.

PMID- 9610083
TI  - 46 XX male: a case of sex reversal syndrome.

PMID- 9610084
TI  - de Lange syndrome.

PMID- 9610085
TI  - Percutaneous nephrostomy: a non-operative management of urinomas: 2 case reports.

PMID- 9610086
TI  - Prevention of pre-eclampsia--is it possible?

PMID- 9610087
TI  - Ectopic pregnancy: an analysis of 62 cases.
AB  - Sixty-two cases of ectopic pregnancy admitted in the Department of Obstetrics and
      Gynaecology, Jinnah Postgraduate Medical Centre, Karachi from July, 1989 to
      December, 1990 were analysed to determine the incidence, risk factors, diagnostic
      features and management. During this period a total number of 10,798 patients
      were delivered giving an incidence of 1:174 births or 5.7 per 1000 births. In
      48.3% cases the cause was unknown, 16.1% followed by pelvic inflammatory disease,
      16.1% had history of D & E for abortion, 6.4% had history of different type of
      pelvic surgery, 4.8% had IUCD in situ, 1.6% had recurrent ectopic pregnancy.
      Diagnosis was made clinically in 80.6% cases. Culdocentesis was performed in all
      cases except one and was diagnostic in 90.1% cases. Ultrasound was performed in
      51 cases and showed positive results in 90.1% cases. Laparoscopy was performed in
      only 10 cases and had 100% accurate results. After thorough re-suscitation
      laparotomy was performed in all cases. Partial salpingectomy was done in 53.2%,
      salpingectomy and tubal ligation in 32.2%. (They had already completed their
      family) and salpingo-oophorectomy in 4.8% cases. Tubes were conserved in 6.2%
      cases (all of them were primigravidas). In single abdominal pregnancy, dead fetus
      and placenta was removed from the peritoneal cavity very carefully. The mortality
      rate in this study was 1.6%.

PMID- 9610088
TI  - A comparison of severe pre-eclampsia/eclampsia in patients with and without HELLP
      syndrome.
AB  - BACKGROUND: The relationship of Haemolysis, Elevated Liver Enzymes and Low
      Platelets (HELLP) syndrome with maternal and perinatal health and its
      presentation in Pakistani population is not known. PURPOSE: To determine the mode
      of presentation along with maternal and perinatal outcome of patients with HELLP
      syndrome. METHODS: Case records of patients with severe hypertension in pregnancy
      who delivered between January 1, 1989 and December 31, 1994 at The Aga Khan
      University Hospital, Karachi. Out of 120 cases of severe pre-eclampsia/eclampsia,
      there were 36 cases of HELLP syndrome (Group-A). These were then compared with
      cases without HELLP syndrome (Group B) for their mode of presentation along with
      maternal and perinatal morbidity and mortality. RESULTS: The overall incidence of
      HELLP syndrome was 0.4%. In the antepartum factors; unbooked status (66% vs 30%;
      p < 0.05), diastolic B.P. > 120 mmHg (61% vs 16%; p < 0.05) DIC (13% vs 2%; p =
      0.03), seizures (40% vs 16%, p = 0.01) and ARF (11% vs 1%, p = 0.07) were
      significantly raised. In the intrapartum factors there were no significant
      differences between the two groups in mode of delivery and complications of
      delivery. Neonatal outcomes did not differ significantly in the two groups.
      CONCLUSIONS: Women with severe hypertension in pregnancy manifesting with HELLP
      syndrome show a significantly greater frequency of developing DIC, seizures and
      acute renal failure. Therefore, their care necessitates intensive monitoring to
      preclude development of these complications.

PMID- 9610089
TI  - Magnesium status in maternal and cord blood.
AB  - Magnesium (Mg) was assessed at term in maternal and cord blood in 52 women and 15
      age matched non pregnant controls and its correlation was studied with Zn, Cu, Ca
      and P. Mean Mg levels in maternal and cord blood when compared with controls was
      not significantly different. A negative correlation was observed between birth
      weight and Mg levels. The levels were higher (P < 0.05) in the cord blood of new
      borns weighing less than 3 kgs as compared to those weighing more than 3 kgs. Mg
      levels were significantly higher in the cord blood of primiparas (P < 0.05) and
      mothers aged less than 20 years (P < 0.05). A positive correlation was observed
      between Mg and zinc (P < 0.01). Mg levels did not differ between a male and
      female child.

PMID- 9610090
TI  - An epidemiologic study of cystitis among Muslim women attending an out-patients
      clinic in Karachi.
AB  - Cystitis is considered to be one of the most common infections afflicting women
      of all age groups. It has been suggested that personal hygiene customs may
      influence the prevalence of cystitis. In this study, 130 women of child bearing
      age attending the out-patients clinic were interviewed in order to determine the
      frequency of cystitis and its associated risk factors including personal hygiene
      practices. Twenty seven percent of the women reported suffering from cystitis
      atleast once in the past, comparable to reported studies from the United States
      but higher than reported from other Muslim countries. Sixty-three percent of
      women reported their first episode during pregnancy and a significant
      relationship was observed between parity and cystitis (p value < 0.000). However,
      personal hygiene practices following micturition or sexual intercourse bore no
      significant association with cystitis. Cystitis, commonly reported among
      Pakistani married women, occurs primarily during pregnancy. Preventive measures
      during pregnancy are suggested.

PMID- 9610091
TI  - Variations in ocular pressure during menstrual cycle.
AB  - The present study investigated whether a correlation between days of the
      menstrual cycle and variations in intraocular pressure exists or not. The number
      of days since the beginning of last menses was recorded along with intraocular
      pressure for 1,459 women. Measurements were taken by Goldmann applanation
      tonometer. The differences among various days of menstrual cycle were
      statistically insignificant. The highest mean IOP occurred between 20th and 22nd
      day and the second peak from 13th to 15th days of the cycle. The lowest mean IOP
      was found from 16th to 19th days of the cycle. This study concludes that
      intraocular pressure varies with the various days of the menstrual cycle, but
      fluctuations are statistically insignificant and cannot affect the diagnoses of
      glaucoma.

PMID- 9610092
TI  - Effects of first and second trimester vaginal bleeding on pregnancy outcome.
AB  - The effects of vaginal bleeding during first and second trimester on pregnancy
      outcomes was assessed in a hospital-based population of 268 non-diabetic women.
      The group of non-bleeders comprised 173 females whereas, there were 71 females
      with first and 24 with second trimester bleeding. Fetal loss (abortion) occurred
      in 34% of first trimester and 25% of second trimester bleeders. Low birth weight
      and preterm delivery were significantly associated with second trimester
      haemorrhage. The results suggest that first and second trimester vaginal bleeding
      correlates with adverse infant outcomes.

PMID- 9610093
TI  - Complications attributed to illicit abortions.
AB  - A four year prospective study was carried out involving 83 cases of induced
      abortions, 72 were induced illegally and 11 were medically indicated, to
      determine the incidence and types of complications of illegally induced abortions
      as well as those of therapeutic ones. The prevalence of illegal abortion was
      3.61% and that of therapeutic was 0.55%. In illegally induced group, age of 48
      (66.66%) women ranged between 21-35 years, 34 (47.22%) were grand multiparas and
      79% were illiterate. In 31 (43.25%) women, illegal abortions were carried out by
      TBAs and the most commonly used method was instrumentation employed in 46
      (63.88%) of cases. The commonest complication detected was haemorrhage occurred
      in 31 (43.25%) patients, followed by sepsis in 24 (33.33%) and trauma in 13 (18%)
      cases. Indications of therapeutic abortions included maternal malignant diseases
      and fetal anomalies. Only one patient developed post abortal endometritis.

PMID- 9610094
TI  - The role of diet in allergic dermatoses.

PMID- 9610096
TI  - Importance of correct interpretation of postmortem artifacts in medicolegal
      autopsies.
AB  - PURPOSE: To study whether various injuries labelled as antemortem are in fact
      postmortem artifacts. STUDY SUBJECTS: 780 postmortems conducted in mortuary of
      S.M.C. Karachi from 1-1-95 to 20-9-95. MAIN FINDINGS: Out of 780 autopsies, 229
      showed postmortem artifacts which included decomposition in 78, animal and
      insects producing changes in 45, injuries due to rough handling in 40, breaking
      of rigor mortis and shifting of postmortem lividity during transportation in 37,
      iatrogenic fracture of skull during opening in 15, fractured ribs during
      resuscitation after death in 8 and exhumation producing fractures of bones in 6
      bodies.

PMID- 9610095
TI  - Acquired arterio-venous fistula with mycetoma: two entities coinciding: a case
      report.

PMID- 9610097
TI  - Pattern of female genital tract malignancy at a private tertiary hospital.

PMID- 9610098
TI  - Psammoma bodies in a cervical smear in association with borderline ovarian
      epithelial malignancy.

PMID- 9610099
TI  - Retinoic acid syndrome: a potentially fatal side effect of retinoic acid therapy.

PMID- 9610100
TI  - Blindness in postpartum period: spinal analgesia or pre-eclampsia caused it?

PMID- 9610101
TI  - Diffuse esophageal spasm: transforming into achalasia.

PMID- 9610102
TI  - Range of validity of alpha and beta for a generalized diversity index H (alpha,
      beta) due to Good.
AB  - Good (I. J. Good, Biometrika 40 (1953) 237; J. Am. Statist. Assoc. 77 (1982) 561)
      proposed a diversity index H (alpha, beta), defined for non-negative integer
      alpha and beta, which generalized the well-known indices of Shannon and Simpson.
      In this paper we further generalize Good's index by allowing the parameters alpha
      and beta to take values in the real plane. For two simple properties which a
      'good' diversity index should possess, we determine the range of valid alpha and
      beta values for this generalized index.

PMID- 9610103
TI  - Optimal harvesting with both population and price dynamics.
AB  - We consider the effects of large inflationary price fluctuations on the computed
      optimal harvest strategy for a randomized Schaefer model. Both prices and
      population sizes are assumed random with both background (Wiener) and jump
      (Poisson) components. Population fluctuations are assumed to be density
      independent, i.e., relative changes are independent of population size.
      Stochastic dynamic programming is employed to find the optimal harvesting effort
      and economic return for a realistic set of bioeconomic data for Pacific halibut.
      It is found that inflationary effects have a pronounced influence on the optimal
      return, even in a hazardous or disastrous environment. However, optimal
      harvesting effort levels are much less sensitive to inflationary effects.

PMID- 9610104
TI  - Model of plasmid-bearing, plasmid-free competition in the chemostat with nutrient
      recycling and an inhibitor.
AB  - In this paper, we consider competition between plasmid-bearing and plasmid-free
      organisms with nutrient recycling and an inhibitor in a chemostat-type systems.
      We discuss the cases where the nutrient is supplied at a constant rate and the
      nutrient supply is time-dependent. For each case, we obtain criteria for the
      boundedness of solutions and persistence.

PMID- 9610105
TI  - Infectious disease transmission and infection-dependent matching.
AB  - This paper uses commonly available prevalence estimates to bound future
      incidence. The bounds rely on restricting the fraction of contacts between
      individuals of different infection statuses. It is argued that these bounds can
      be further tightened by restrictions of economic models of infectious disease
      that imply that uninfected individuals have larger incentives to avoid matching
      with infected individuals than do the infected individuals themselves. This
      implies that incidence predictions from canonical models of infectious disease
      are worst-case upper bounds, with the degree to which they overestimate new cases
      being monotonically related to this type of infection-dependent matching.
      Evidence in support of the economic type of infection-dependent matching is
      presented, by using data on the joint distribution of partners' HIV statuses in a
      random sample of couples from San Francisco in 1988-1989.

PMID- 9610106
TI  - A model for hepatocarcinogenesis treating phenotypical changes in focal
      hepatocellular lesions as epigenetic events.
AB  - The major paradigm for mathematically describing the carcinogenic process has
      been through the use of multistage models. Multistage models are made up of
      numerous compartments representing cells in various stages on the way to
      malignancy and where movement from one cell class to another is assumed to have
      exponential waiting time. Once a cell is in a particular class, clonal expansion
      through a linear birth-death process increases the size of the compartment. These
      models are characterized by movement of single cells from one compartment to
      another rather than clonal colonies of cells. However, there is some evidence to
      suggest that, in certain organs for certain types of agents, preneoplastic
      lesions with different phenotypes arise directly from an entire clonal colony
      rather than from a single cell within that colony. This manuscript describes a
      simple mathematical model of carcinogenesis using both persistent changes of
      single or several cells (to start the process) and shifting of colonies to
      describe the stages of the model. Likelihoods for the use of the model with data
      on colonies of preneoplastic lesions are described and applied to real data.

PMID- 9610107
TI  - Unique wave front for dendritic spines with Nagumo dynamics.
AB  - A model of dendritic spines uniformly distributed along a dendrite cable with the
      Nagumo dynamics for active membrane spine activity is considered. We show
      analytically the existence and uniqueness of traveling front solutions for a wide
      range of parameters including the spine density and the resistance between spine
      heads and dendrites. And such wave front travels at a slower speed for a larger
      spine density. Numerical simulations support the above results.

PMID- 9610108
TI  - Multiple nutrient limitation in unicellulars: reconstructing Liebig's law.
AB  - Liebig's law of the Minimum is reformulated in terms of biomass composition
      dynamics. The doctrine of the single limiting nutrient is shown to be invalid
      generally. The nutritional status of a unicellular organism is expressed in terms
      of state variables; one which represents the subsistence composition and a number
      of reserve surplus type variables. It is proposed that the property of being
      limiting should be defined in terms of the reserve surplus variables. On the
      basis of this definition, it can be decided whether a nutrient, or combination of
      nutrients, is limiting, both in transient and steady states. The concept of
      multiple limitation is shown to have two distinct meanings on these definitions.
      A non-interactive minimum model, based on a 'hard' minimum operator, is
      introduced. Smooth interactive models may be formulated which have this minimum
      model as a limiting case. One such model is described. Numerical simulations show
      how the behaviour of this smooth model can approximate that of the minimum model:
      apparently hard non-linearities can arise in the smooth model, through time-scale
      separation.

PMID- 9610109
TI  - The dynamics of an infectious disease in a population with birth pulses.
AB  - In most models of population dynamics increases in population due to births are
      assumed to be time-independent, but many species of wild animal give birth only
      during a single period of the year. We propose a model for the dynamics of a
      fatal infectious disease in a wild animal population for which births occur in a
      single pulse once per time period. Periodic solutions are found and criteria for
      their stability determined. A simple example applied to tuberculosis in the
      possum is used to illustrate the effect of the birth pulse on critical population
      parameters.

PMID- 9610110
TI  - Age-density dependent population dispersal in RN.
AB  - We discuss an N-dimensional model for diffusion of age dependent populations. Let
      rho(x, t, a) be the population density at time t, age a and spatial position x,
      and let u(x, t) = [formula: see text] rho(x, t, a) da be the total population at
      t and x. The directed dispersal model to be discussed, with diffusion depending
      on the gradient of the total population, is [formula see text] With some
      assumptions on the form of the death and birth modulus, this system is reduced to
      a mixed parabolic-hyperbolic system containing the Porous Medium equation in RN.
      We discuss the existence, regularity and localization of the solution of this
      reduced system.

PMID- 9610111
TI  - Modeling and analysis of a marine bacteriophage infection.
AB  - A mathematical model for the marine bacteriophage infection is proposed and its
      essential mathematical features are analyzed. Since bacteriophage infection
      induces bacterial lysis which releases into the marine environment, on the
      average, 'b' viruses per cell, the parameter b epsilon (1, t infinity) or 'virus
      replication factor' is chosen as the main parameter on which the dynamics of the
      infection depends. We proved that a threshold b* exists beyond which the endemic
      equilibrium bifurcates from the free disease one. Still, for increasing b values
      the endemic equilibrium bifurcates toward a periodic solution. We proved that a
      compact attractor set omega within the positive cone exists and within omega the
      free disease equilibrium is globally stable whenever b < or = b*, whereas it
      becomes a strong uniform repeller for b > b*. A concluding discussion with
      numerical simulation is then presented.

PMID- 9610112
TI  - A lineal equation for the classification of progressive and hyperactive
      spermatozoa.
AB  - Capacitation of spermatozoa, a complex sequence of events that render them able
      to fertilize the egg, is generally associated with a switch from lineal,
      progressive movement to a vigorous, non-progressive pattern characterized by
      starlike tracks, a process known as hyperactivation. Development of a method for
      the analysis of progressive and hyperactive tracks is thus important for the
      assessment of capacitation in biochemical, physiological and clinical studies. In
      this study, we have applied a two-step heuristic model to deduce a lineal
      equation that discriminates hyperactive from progressive spermatozoa. The kinetic
      parameters (curvilinear velocity (VCL), linearity (LIN), amplitude of lateral
      head displacement (ALH), straightness (STR), wobble (WOB), mean 'dance' (DAN) and
      velocity of the average path (VAP)) of ram spermatozoa were evaluated with a
      computerized motility analyzer, and classified one by one as progressive or
      hyperactive by the appearance of their tracks. In a first step, a discriminating
      plane was defined by minimizing the number of misclassified spermatozoa
      ('conflicting points'); then, the plane was adjusted by an iterative process to
      minimize the distance from conflicting points to it. The resulting plane showed a
      discriminating capacity of over 95% for both classes, higher than that achieved
      by setting a threshold value for the parameters taken separately or in group.
      When included in a standard semen analysis, application of the equation allowed a
      rapid assessment of the percentage of hyperactive spermatozoa. The method
      described, developed in ram spermatozoa, can be applied to different species for
      a variety of purposes.

PMID- 9610113
TI  - A stochastic model of cellular transformation and its relevance to chemical
      carcinogenesis.
AB  - A mathematical model is presented which determines the relationship of cellular
      mutation to cellular survival and transformation. The basis for this model is the
      hypothesis that the entropy associated with changes of genotype are linearly
      proportional to the entropy associated with changes in phenotype. This hypothesis
      leads to a mathematical derivation relating cellular survival, mutation and
      transformation. The relevance of this model to data derived from experiments in
      chemical carcinogenesis is presented.

PMID- 9610114
TI  - Novel popout without novelty.
AB  - Localization of a novel word in an array with several familiar words is typically
      enhanced relative to localization in an all-novel array (between-array novel
      popout) and sometimes enhanced relative to familiar words in one-novel arrays
      (within-array novel popout). Christie and Klein (1996) have questioned the
      reality of the latter effect, suggesting that it may be an artifact of guessing
      bias. The present Experiment 1 replicated within-array novel popout with the
      novel word probed at chance (i.e., on only one quarter of trials). Experiments 2
      and 3 demonstrated a similar popout effect for a categorically unrelated word
      among three categorically related words, despite superior performance on all
      related arrays relative to all-unrelated arrays. Repetition of constant sets of
      words within the experimental context is therefore unnecessary for a popout
      effect, contrary to assertions by Johnston and Hawley (1994). Interitem
      associations appear to be sufficient to produce a popout effect; as such, "novel
      popout" appears to be a misnomer for a phenomenon that does not depend on
      novelty.

PMID- 9610115
TI  - Long-term positive and negative identity priming: evidence for episodic
      retrieval.
AB  - An episodic retrieval account of negative priming (Neill, 1997; Neill & Valdes,
      1992) was evaluated in three experiments. During practice, regular word pairs
      were presented to subjects differing numbers of times. The subjects named
      specific target words while they ignored specific distractor words. Following a 5
      min retention interval, memory for practice was revealed: Test responses for
      target words exhibited positive priming that increased with increases in the
      number of times that the words had been attended. Test responses for distractor
      words exhibited either positive priming (Experiment 1) or negative priming
      (Experiments 2-3) that also increased with increases in the number of times that
      the words had been ignored. The type of priming that distractors exhibited was
      determined by several contextual similarities between the practice environment,
      in which distractors were ignored initially, and the test environments, in which
      they were processed subsequently. Negative priming that spanned a 5-min interval,
      increased with increases in the number of times that a distractor was ignored,
      and was sensitive to contextual changes indicated that the direction of the
      effect was temporally backward because the test probe cued memory for earlier
      processing of the priming stimulus when the distractor had been ignored.

PMID- 9610116
TI  - The gender difference on the Mental Rotations test is not due to performance
      factors.
AB  - Men score higher than women on the Mental Rotations test (MRT), and the magnitude
      of this gender difference is the largest of that on any spatial test. Goldstein,
      Haldane, and Mitchell (1990) reported finding that the gender difference on the
      MRT disappears when "performance factors" are controlled--specifically, when
      subjects are allowed sufficient time to attempt all items on the test or when a
      scoring procedure that controls for the number of items attempted is used. The
      present experiment also explored whether eliminating these performance factors
      results in a disappearance of the gender difference on the test. Male and female
      college students were allowed a short time period or unlimited time on the MRT.
      The tests were scored according to three different procedures. The results showed
      no evidence that the gender difference on the MRT was affected by the scoring
      method or the time limit. Regardless of the scoring procedure, men scored higher
      than women, and the magnitude of the gender difference persisted undiminished
      when subjects completed all items on the test. Thus there was no evidence that
      performance factors produced the gender difference on the MRT. These results are
      consistent with the results of other investigators who have attempted to
      replicate Goldstein et al.'s findings.

PMID- 9610117
TI  - Retrieval dynamics in recognition and list discrimination: further evidence of
      separate processes of familiarity and recall.
AB  - Two experiments tested the hypothesis that the time course of retrieval from
      memory is different for familiarity and recall. The response-signal method was
      used to compare memory retrieval dynamics in yes-no recognition memory, as a
      measure of familiarity, with those of list discrimination, as a measure of
      contextual recall. Responses were always made with regard to membership in two
      previous study lists. In Experiment 1 an exclusion task requiring positive
      responses to words from one list and negative responses to new words and words
      from the nontarget list was used. In Experiment 2, recognition and list
      discrimination were separate tasks. Retrieval curves from both experiments were
      consistent, showing that the minimal retrieval time for recognition was about 100
      msec faster than that for list discrimination. Repetition affected asymptotic
      performance but had no reliable effects on retrieval dynamics in either the
      recognition or the list-discrimination task.

PMID- 9610118
TI  - The role of item distinctiveness in short-term recall of order information.
AB  - In two experiments, we examined short-term recall of order information using a
      partial-report distractor task. We manipulated the characteristics of a single
      letter in one of two four-letter segments. Participants knew in advance the
      identity of the letters in each segment. We made a single letter distinctive at
      presentation either by printing it in red or by replacing it with a red dash.
      Presenting the letter in red did not affect overall recall of the positions of
      the letters in the segment but did facilitate specific recall of the position of
      the distinct letter. Replacing the letter with a red dash inhibited overall
      recall as well as specific recall of the distinct letter. Participants were also
      less likely to respond in the regular output order when there was a dash
      replacing a letter in the segment. These effects of distinctiveness are explained
      in terms of output order processes in recent versions of the perturbation model.

PMID- 9610119
TI  - Creating proactive interference in immediate recall: building a dog from a dart,
      a mop, and a fig.
AB  - Phonemic codes are accorded a privileged role in most current models of immediate
      serial recall, although their effects are apparent in short-term proactive
      interference (PI) effects as well. The present research looks at how assumptions
      concerning distributed representation and distributed storage involving both
      semantic and phonemic codes might be operationalized to produce PI in a short
      term cued recall task. The four experiments reported here attempted to generate
      the phonemic characteristics of a nonrhyming, interfering foil from unrelated
      filler items in the same list. PI was observed when a rhyme of the foil was
      studied or when the three phonemes of the foil were distributed across three
      studied filler items. The results suggest that items in short-term memory are
      stored in terms of feature bundles and that all items are simultaneously
      available at retrieval.

PMID- 9610121
TI  - Prime time advertisements: repetition priming from faces seen on subject
      recruitment posters.
AB  - Repetition priming is defined as a gain in item recognition after previous
      exposure. Repetition priming of face recognition has been shown to last for
      several months, despite contamination by everyday exposure to both experimental
      and control faces in the interval. Here we show that gains in face recognition in
      the laboratory are found from faces initially seen in a rather different context-
      on subject recruitment posters, even when the advertisements make no specific
      mention of experiments involving face recognition. The priming was greatest when
      identical pictures were shown in the posters and in the test phase, although
      different views of faces did give significant priming in one study. Follow-up
      studies revealed poor explicit memory for the faces shown on the posters. The
      results of these experiments are used to develop a model in which repetition
      priming reflects the process of updating representations of familiar faces.

PMID- 9610120
TI  - Simulating individual word identification thresholds and errors in the
      fragmentation task.
AB  - This article presents a large-scale study that collected word identification
      thresholds and errors in the fragmentation task for all four-letter French words.
      In the first part of this article, we identify some of the variables (e.g., word
      frequency, neighborhood size, letter confusability) that affect performance in
      the fragmentation task. In the second part, we analyze individual response
      performance and identify different response strategies. We demonstrate that the
      interactive activation model can account for individual response strategies by
      adapting two of its original parameters: word-letter feedback and letter-word
      inhibition. In the third part, we demonstrate that the adaptation of the
      interactive activation model to the fragmentation task makes it possible to
      successfully simulate a facilitatory frequency effect on identification
      thresholds, an inhibitory neighborhood size effect on error rates, and an
      inhibitory letter confusability effect on identification thresholds. When the
      task-specific processes of the fragmentation task are specified and individual
      response strategies are considered, the interactive activation model provides a
      parsimonious architecture for modeling the task-independent processes involved in
      word perception.

PMID- 9610122
TI  - Flashbulb memories and the underlying mechanisms of their formation: toward an
      emotional-integrative model.
AB  - Flashbulb memories (FBMs) are detailed recollections of the context in which
      people first heard about important events. The present study investigates three
      models of the formation and maintenance of FBM. Two models have previously been
      proposed in the literature (Brown & Kulik, 1977; Conway et al., 1994). A third
      model of FBM that integrates theories of FBM and recent developments in the field
      of emotions is proposed. The present study compares these three competing models
      by investigating the FBMs that Belgian citizens developed upon learning of the
      unexpected death of their king Baudouin. Structural equation modeling revealed
      that, as compared to the two previously proposed models, the third model, which
      takes into account emotional processes, better explains FBM.

PMID- 9610123
TI  - A year's memories: the calendar effect in autobiographical recall.
AB  - When asked to recall autobiographical events from the past year, students tend to
      recall more incidents from the beginning and the end of school terms than from
      other periods. We investigated this calendar effect in Experiment 1 by comparing
      free recall at schools with different academic calendars. The event distributions
      tracked the individual calendars, helping to eliminate the possibility that the
      calendar effect is due to seasonal, nonschool factors, such as holidays. In
      Experiments 2-4, we checked explanations based on the ideas that events at term
      boundaries are more important or distinctive than others, that events are
      incorrectly dated too near the boundaries, and that boundaries serve as implicit
      cues for recall. These experiments revealed no evidence that importance or errors
      in dating could explain the effect. Manipulating cues, however, did change the
      size of the effect, implicating retrieval from very long-term memory as the
      effect's source. We suggest that when people have to search episodic memory, they
      consider their own calendar rhythms (such as a student's academic schedule) and
      let the temporal structure of their personal context guide their search.

PMID- 9610124
TI  - Effects of target set size on feelings of knowing and cued recall: implications
      for the cue effectiveness and partial-retrieval hypotheses.
AB  - Target set size refers to the number of preexisting connections a studied word
      has to closely related concepts in long-term memory. The purpose of this
      investigation was to determine whether target set size influences feeling-of
      knowing (FOK) ratings. The results showed that ratings were higher for targets
      connected to smaller sets, as compared with those connected to larger sets.
      Comparable effects were obtained with the use of different encoding strategies,
      including concreteness classifications and vowel naming, and with both
      meaningfully and phonologically related test cues. These findings indicate that
      FOKs are sensitive to competition between concepts linked to the target and that
      this sensitivity is independent of encoding strategy and type of test cue.
      Response time measures indicated that FOKs are sensitive to competition that
      arises when concepts are activated in parallel, whereas recall is more sensitive
      to competition that arises during sampling associated with search. Implications
      for various cue-based and target-based explanations of FOK effects are discussed.

PMID- 9610125
TI  - Effect of normal aging on the manipulation of information in working memory.
AB  - The goal of this study is to examine the central executive of working memory in
      normal aging, specifically focusing on its capacities to manipulate or modify the
      format of the to-be-recalled material. The central executive was measured with
      the alphabetical span procedure, during which subjects were asked to recall a
      random series of words in their alphabetical order. The storage demand was
      equalized across subjects by adjusting the list lengths according to individual
      span. Experiments 1, 2, and 3 showed that elderly subjects were not impaired in
      manipulating information, relative to young controls, even when the difficulty of
      the task was increased. In Experiment 4, validity was tested by asking young
      subjects to perform the task under the conditions of full or divided attention.
      Alphabetical recall was more impaired than direct recall during the divided
      attention condition, which suggests a larger involvement of the central executive
      component in the former. These results are discussed in relation to the
      hypothesis of a central executive impairment being associated with normal aging.

PMID- 9610126
TI  - A "word length effect" for sign language: further evidence for the role of
      language in structuring working memory.
AB  - We report a sign length effect in deaf users of American Sign Language that is
      analogous to the word length effect for speech. Lists containing long signs
      (signs that traverse relatively long distances) produced poorer memory
      performance than did lists of short signs (signs that do not change in location).
      Further, this length effect was eliminated by articulatory suppression
      (repetitive motion of the hands), and articulatory suppression produced an
      overall drop in performance. The pattern of results, together with previous
      findings (Wilson & Emmorey, 1997), provides evidence for a working memory system
      for sign language that consists of a phonological storage buffer and an
      articulatory rehearsal mechanism. This indicates a close equivalence of structure
      between working memory for sign language and working memory for speech. The
      implications of this equivalence are discussed.

PMID- 9610127
TI  - Voice-specificity effects on auditory word priming.
AB  - This research explores the nature of the memory traces that support spoken word
      identification. Specifically, do voice-specificity effects in implicit memory
      depend on information in a perceptual representational system or, alternatively,
      on the similarity of study and test exemplars? Memory for words and voices was
      assessed with two perceptual identification tests--the identification of words in
      noise and the identification of low-pass filtered words--after two encoding
      conditions (identification of words in noise and of words in the clear). At test,
      a word was presented in the same voice as at study or in a different voice. The
      data from the two experiments showed that study-to-test changes in voice reduced
      priming and that voice-specificity effects were greatest when the type of
      processing engaged at study overlapped with that required at test. Taken
      together, the results implicate the goodness of the processing match between
      encoding and test as the primary determinant of voice-specificity effects on
      perceptual identification tests and support the hypothesis that both voice and
      word information is represented within a single episodic memory system.

PMID- 9610128
TI  - Accessing singular antecedents in conjoined phrases.
AB  - Two experiments examined processing of singular pronouns when the antecedent
      (e.g., Mary) was a noun phrase (NP) in a conjoined phrase (e.g., Mary and John).
      Whole-sentence reading times showed an increase in processing time associated
      with splitting the conjoined phrase to access a single NP antecedent. The
      increase in processing occurred both when the antecedent was in the subject
      position and when it was in a nonsubject position. The source of the disruption
      was further investigated using eyetracking methods. Summing over regions of the
      text, the magnitude of the processing cost incurred by having to split a
      conjoined NP was closely comparable when there was and when there was not a
      gender-appropriate distracting potential antecedent. When there was no such
      potential antecedent, the increase in processing time occurred immediately in the
      pronoun region when eye movements were measured. In contrast, when there was a
      second discourse entity that matched the gender and number of the pronoun (but
      was not a plausible antecedent for the pronoun), eyetracking measures suggested
      that the processing difficulty was delayed until additional information was read
      that forced the antecedent to be one of the conjoined NPs. The results are
      interpreted in terms of Sanford and Garrod's (1981) scenario-based model of text
      comprehension.

PMID- 9610130
TI  - Deep-seated fungal diseases in the South Pacific, especially in New Caledonia.
AB  - The main deep-seated fungal diseases and their encountered pathology in New
      Caledonia and other islands of the South Pacific are reviewed (1970-96).
      Cryptococcosis is encountered in all islands of the South Pacific, Australia and
      Papua New Guinea, with a predominance of variety gattii, which is associated with
      some species of Eucalyptus. Histoplasmosis is not uncommon, and there was an
      epidemic in New Caledonia in 1994 among people who had visited a bat-inhabited
      cave. Mycetomas, in particular presenting as pale granules in tissues, are
      encountered in New Caledonia, Vanuatu, Papua New Guinea, Fiji and French
      Polynesia. Other fungal infections, such as zygomycosis, sporotrichosis (three
      cases) and chromomycosis (six cases) are rarely observed in New Caledonia.

PMID- 9610129
TI  - Experimental models in antifungal chemotherapy.

PMID- 9610131
TI  - Isolates of Cryptococcus neoformans serotype A and D developed on canavanine
      glycine-bromthymol blue medium.
AB  - Two isolates of Cryptococcus neoformans serotype A and one isolate of serotype D
      from pigeon droppings were found to grow on canavanine-glycine-bromthymol blue
      (CGB) medium, when the Japanese isolates of Cr. neoformans were examined for
      their serotype and biochemical characteristics. The susceptibility to canavanine
      and the activity in assimilation of glycine were analysed on these three
      isolates. They were resistant to canavanine at the high concentration of 3.6 mmol
      l-1 and developed by assimilating the glycine even at a concentration of 7 mmol l
      1. These isolates were proved to develop well on CGB medium, which contains 0.1
      mmol l-1 of canavanine and 133 mmol l-1 of glycine. Three isolates of Cr.
      neoformans developed on CGB medium were also confirmed to be serotype A or D by
      the molecular analysis.

PMID- 9610132
TI  - Susceptibility testing of Cryptococcus neoformans using the urea broth
      microdilution method.
AB  - An urea broth microdilution method to assay the susceptibility of Cryptococcus
      neoformans to antifungal drugs was newly developed. Using this method, urease
      activity of the fungus was measured instead of the viability by checking colony
      development. The urease activities were indicated by colour changes in optical
      density at 545 nm. The end point in this assay was considered as 99% inhibitory
      concentration. When we measured antifungal activities of the three drugs against
      16 isolates of Cr. neoformans using this assay method, mean minimum-inhibitory
      concentrations (MICs) of fluconazole, itraconazole and terbinafine were 2.0
      micrograms ml-1, 0.008 microgram ml-1 and 0.25 microgram ml-1 respectively. This
      assay method resulted in higher sensitivity in MICs of the three antifungal drugs
      than the broth microdilution method recommended by the Committee for Laboratory
      Standards of the Japanese Society for Medical Mycology. The results obtained
      using this assay method support the more effective evaluation of antifungal
      substances in susceptibility testing of Cr. neoformans.

PMID- 9610133
TI  - Rhinocerebral zygomycosis treated with liposomal amphotericin B and surgery.
AB  - We report three cases with rhinocerebral zygomycosis in two diabetic persons and
      one otherwise healthy person. The diagnosis was established by histopathological
      appearance and computerized tomography (CT) and/or magnetic resonance imaging
      (MRI) scans. These cases were successfully treated by a combination of surgery
      and liposomal amphotericin B.

PMID- 9610134
TI  - Rhinocerebral zygomycosis.
AB  - An unusual case of rhinocerebral zygomycosis with its clinical and
      histopathological features are presented. A good response was observed with oral
      itraconazole at a dose of 200 mg day-1 for a period of 3 months. To our
      knowledge, it is the first case report of this infection, involving the maxillary
      sinus, eye and the brain, from Madras, Tamilnadu, India.

PMID- 9610135
TI  - Entomophthoromycosis in India--a 4-year study.
AB  - Ten cases of entomophthoromycosis encountered in a period of 4 years in Tamilnadu
      are reported. Basidiobolomycosis accounted for eight cases and was seen
      predominantly in children. Two cases of conidiobolomycosis were seen in elderly
      patients. Potassium iodide was the drug of choice in the treatment of
      entomophthoromycosis. All our patients, except one, responded with complete
      resolution of their lesions.

PMID- 9610137
TI  - Long-term post-treatment follow-up of onychomycosis treated with terbinafine: a
      multicentre trial.
AB  - Between 1991 and 1993, 32 cases of fingernail mycosis and 20 cases of toenail
      mycosis caused by dermatophytes were treated with terbinafine. For 8 weeks, 250
      mg of terbinafine was given daily for fingernail infections, and for 12 weeks the
      same dose was given for toenail involvement; the short-term follow-up was 24 and
      48 weeks respectively. A long-term follow-up was performed twice, initially at 24
      and then at 48 months after the end of the treatment. For fingernail mycosis, the
      mycological cure rate was 100% at the end of month 24 and 91% at the end of month
      48. Mycological cultures gave negative results in toenail infections in 90% after
      24 months and in 86% after 48 months. After 24 months, 23 out of 26 patients
      (88%) with fingernail and 17 out of 20 patients (95%) with toenail mycosis were
      clinically cured. After 48 months, 20 out of 22 cases (91%) with fingernail and
      10 out of 14 cases (71%) with toenail involvement showed a complete cure.

PMID- 9610136
TI  - Disseminated Fusarium solani infection with endocarditis in a lung transplant
      recipient.
AB  - Eleven days after double lung transplantation for cystic fibrosis, an 18-year-old
      patient developed a disseminated Fusarium solani infection with tricuspid valve
      endocarditis. This infection occurred under fluconazole and immunosuppressive
      therapy with cyclosporin, prednisone and azathioprine, with a normal leucocyte
      count. Liposomal amphotericin B allowed blood culture negativation. The patient
      died from a bacterial septic shock.

PMID- 9610138
TI  - Clinical and diagnostic aspects of dermatophyte onychomycosis.
AB  - The paper presents mechanisms of the spread of dermatophyte infection in the nail
      and the associated most frequently encountered clinical features. Particular
      attention has been paid to advantages for dermatological practice that are based
      on using some diagnostic traits of dermatophyte onychomycosis, in particular
      signs of a transverse and spriggy network, typical of the disease.

PMID- 9610139
TI  - Keratin degradation by Scytalidium species and Fusarium solani.
AB  - The keratin degradation capability of some non-dermatophytic filamentous fungi,
      viz Scytalidium dimidiatum types A and B, S. hyalinum, S. japonicum and Fusarium
      solani, was investigated using nail clippings and keratin powder as substrates.
      Representative isolates of the dermatophytes Trichophyton rubrum and T.
      mentagrophytes were also tested. The two morphological types of S. dimidiatum
      were almost equally effective in the degradation of substrates, 42-43% nail
      clippings and 24-26% keratin. Scytalidium hyalinum and S. japonicum degraded 40%
      and 38% of nail clippings respectively. Degradation of keratin was insignificant.
      In the case of F. solani, nail clippings were degraded 43% and keratin 20%. The
      dermatophytes caused much higher degradation of nail clippings (70-73%) and
      keratin (42-52%).

PMID- 9610141
TI  - Protective efficacy of vaccines against bovine dermatophytosis after double and
      single vaccination.
AB  - The protective efficacy of two Czech vaccines against bovine Trichophyton
      verrucosum infection after double vaccination of calves in prophylactic doses,
      with an interval of 13 days between vaccination and revaccination, was very good.
      When these preparations were applied in a double dose only once, less protective
      effect was produced. The use of 0.5% aluminium hydroxide to dilute the vaccines
      had no influence on the effect of single vaccination.

PMID- 9610140
TI  - A case of tinea barbae successfully treated with terbinafine.
AB  - Terbinafine was remarkably effective in tinea barbae due to Trichophyton rubrum
      on the cheek in front of the right ear in a 75-year-old man. This patient also
      showed tinea pedis and unguium, but these were due to Trichophyton mentagrophytes
      and were unrelated to the tinea in the cheek. This patient showed an atypical
      clinical picture slightly different from that during the initial visit, requiring
      histological differentiation from trichophytic granuloma.

PMID- 9610142
TI  - Effect of aflatoxin ingestion in feed on body weight gain and tissue residues in
      rabbits.
AB  - The effect of a subclinical dose of aflatoxin on body weight gain and risk
      assessment of aflatoxin in muscle tissue for food safety were the focus of the
      study. Thirty New Zealand rabbits, 2 months old, were used. A group of 24 rabbits
      was fed aflatoxin 2 p.p.m. day-1 for a period of 4 months. The weights of the
      individual aflatoxin-fed rabbits and those of the control group were recorded
      weekly. Aflatoxin was withdrawn from a group of six rabbits chosen at random for
      a period of 4 weeks before the termination of the experiment. All rabbits were
      necropsied at the end of the study for gross and microscopic changes of the
      internal organs. Samples of muscle tissue were also collected and analysed
      chemically for aflatoxin using thin-layer chromatography. Significant weight loss
      equivalent to 13% mortality was found in the aflatoxin-fed rabbits.
      Characteristic pathological changes were found. Aflatoxins B1 and G2 were
      detected in muscle tissue at alarming concentrations far exceeding the
      permissible levels in food for human consumption in the aflatoxin-fed group. No
      detectable aflatoxins were found in the aflatoxin-withdrawal group.

PMID- 9610143
TI  - The cultural context of interventions for family members with a seriously
      mentally ill relative.
AB  - This chapter provides an overview of interventions for relatives of severely
      mentally ill individuals. The author discusses the design and use of these
      interventions in the context of the cultural characteristics of families and
      providers, as well as the culture of the interventions themselves.

PMID- 9610145
TI  - Family-to-family: a trauma-and-recovery model of family education.
AB  - A peer educational program sponsored by the National Alliance for the Mentally
      Ill uses a unique combination of healing, consciousness-raising, and empowerment
      to serve long-neglected family needs.

PMID- 9610144
TI  - Reducing the culture clash in family-provider relationships: a bilateral
      perspective.
AB  - This chapter uses the concept of culture clash to take a fresh look at the slow
      progress toward family-provider collaboration. The authors discuss an
      intervention that targets both family culture and provider culture.

PMID- 9610146
TI  - Multicultural experiences of family caregiving: a study of African American,
      European American, and Hispanic American Families.
AB  - There is growing attention to the roles of families as caregivers of relatives
      with serious mental illness. This chapter examines the experiences of family
      caregivers in diverse cultures and discusses the implications of these
      experiences for the goal of supporting families in these roles.

PMID- 9610147
TI  - Support group satisfaction: a comparison of minority and white families.

PMID- 9610148
TI  - Family wisdom and clinical support: culturally relevant practice strategies for
      working with Indochinese families who care for a relative with mental illness.
AB  - Clinical issues in serving Indochinese families with a member with severe mental
      illness are discussed, together with culturally relevant strategies for
      engagement, communication, psychoeducational interventions, and reinforcing
      natural support systems.

PMID- 9610149
TI  - Working with native American families.
AB  - Family education is a respectful approach to working with Native American
      families. When clinicians are informed about tribal ways, families can contribute
      greatly to accurate diagnosis and effective treatment and rehabilitation.

PMID- 9610151
TI  - Perspectives on religion, death.

PMID- 9610150
TI  - The family experience in cultural context: implications for further research and
      practice.
AB  - Cross-cultural studies of families' experience of mental illness are discussed,
      in terms of uniformities in and differences between belief systems and values,
      caregiving norms, perceived burden and distress, and expectations, with
      suggestions for further research and applications to practice.

PMID- 9610152
TI  - Let's keep medicine safe from "intellectual midgets".

PMID- 9610154
TI  - What is the Office of Alternative Medicine and what does it do?

PMID- 9610153
TI  - The role of the medical profession in a managed care environment. Response to
      comments on the Bioethics Committee statement.

PMID- 9610155
TI  - Mind-body medicine. A cautionary note.

PMID- 9610156
TI  - Spirituality and the brain.

PMID- 9610157
TI  - Chaos. A mathematics for heart and mind.

PMID- 9610158
TI  - The spiritual platform. Spirituality and psychotherapy in addiction medicine.

PMID- 9610159
TI  - The mind, the body, health, and disease. What do we know, what should we do?

PMID- 9610160
TI  - Hypnosis. Fact or fiction for treating pain and related disorders?

PMID- 9610161
TI  - Brain and behavior.

PMID- 9610162
TI  - The psychophysiology of ecstasy in Sufism and Yoga.

PMID- 9610163
TI  - Religion and healing. Cultivating a respectful ambivalence.

PMID- 9610164
TI  - Chinese medicine and the life of the mind. Are brains necessary?

PMID- 9610165
TI  - Are men's and women's brains different?

PMID- 9610166
TI  - Iris. UNC students launch a journal for medicine, literature, and visual art.

PMID- 9610168
TI  - Coefficient of accuracy and concordance correlation coefficient: new statistics
      for methods comparison.
AB  - A new statistic, the Coefficient of Accuracy, C(a), has been developed by Lin for
      methods comparison. When an old measurement method is compared to a new
      measurement method or if the same method is compared in two laboratories, the
      Coefficient of Determination, r2, is typically used to measure the relationship.
      However, r2 only measures the precision of the relationship. The newly developed
      statistic, C(a), measures the accuracy of the relationship. When these two
      statistics are combined together, they form a single statistic for both accuracy
      and precision called the Concordance Correlation Coefficient, rc.

PMID- 9610167
TI  - Validation and the human element.
AB  - Frequently the steps in the process which involve human intervention are the weak
      links in the process, the steps representing the highest risk. This is not due to
      lack of training or motivation of people, but to weaknesses in the design of the
      process and to the intrinsic error rate of manual operations. Quite often in
      validation work the human element is ignored while mechanical and technological
      aspects are studied in great detail. This article will include some examples
      about what we have learned about risk where human intervention is involved by
      using Failure Mode Effect Analysis (FMEA) and Process Reengineering
      methodologies. Furthermore, the implications for training and qualification of
      people in the validation context will be discussed.

PMID- 9610169
TI  - Selection of biological indicator for validating microwave heating sterilization.
AB  - For the purpose of selecting an appropriate biological indicator for evaluation
      of the effects of microwave heating sterilization, we examined aerobic bacterial
      spores to determine whether microwaves have non-thermal sterilization effects.
      After microwave irradiation on dry bacterial spores (three species), none of the
      bacterial spores were killed. The survival rate of the spores after microwave
      irradiation of spore suspensions (twelve species) was compared with that after
      heating by a conventional method. The order of heat resistance in the bacterial
      species was similar between the two heating methods. Bacillus stearothermophilus
      spores were the most heat-resistant. These results suggest that microwaves have
      no non-thermal sterilization effects on bacterial spores, the specific resistant
      spores to microwave heating, and microwave heating sterilization can be evaluated
      in the same way as for conventional heating sterilization. As a biological
      indicator for evaluation of overkill sterilization, B. stearothermophilus spores
      may be appropriate for microwave heating sterilization as well as steam
      sterilization.

PMID- 9610170
TI  - Lysis of human red blood cells. 3: Effect of contact time on surfactant-induced
      hemolysis.
AB  - The percent hemolysis induced by various surfactants was determined as a function
      of the formulation composition and formulation: blood contact time using the
      dynamic in vitro method of Krzyzaniak et al. (1). The amount of hemolysis induced
      by nonionic surfactant formulations is shown to be relatively low and to increase
      only slightly with contact time. However, when ionic surfactant formulations are
      used, hemolysis is shown to increase dramatically with surfactant concentration
      and to be sigmoidally related to the logarithm of contact time. Since surfactant
      induced hemolysis is dependent on both the surfactant concentration and the
      contact time, intravascular hemolysis must be evaluated using an in vitro method
      that simulates the intravenous injection site. With this information,
      hemolytically safe surfactant formulations can be developed for intravenous
      administration.

PMID- 9610171
TI  - The effect of closure processing on the microbial inactivation of biological
      indicators at the closure-container interface.
AB  - Two biological indicators are routinely used by the Hospital Products Division to
      demonstrate the sterilization of the closure-container interface. The use of a
      moist heat (Clostridium sporogenes) and a dry heat (Bacillus subtilis) biological
      indicator allows a better understanding of the parameters that impact
      sterilization of the closure-container system. The ability to sterilize a given
      closure-container interface is defined in large part by closure moisture and
      product time above 100 degrees C. The data will demonstrate several different
      means to alter these two key factors, thereby enhancing sterilization of the
      closure-container interface. A categorization of closure types and processing
      parameters allows for more efficient cycle development in the R&D facility and a
      higher success rate for the final subprocess validation in the manufacturing
      steam vessels.

PMID- 9610172
TI  - New hospital regulations meet resistance from physicians.

PMID- 9610173
TI  - Improper use of DEA number again draws physician attack.

PMID- 9610174
TI  - Survival requires more than acceptance.

PMID- 9610175
TI  - The ills of cigar smoking: just the facts, please.

PMID- 9610176
TI  - [The impact factor--what it is and where it is useless].

PMID- 9610177
TI  - [Recombinant allergens for diagnosis of allergic bronchopulmonary aspergillosis].

PMID- 9610178
TI  - [Role of Bcl-xL in cytokine-induced delay of eosinophilia apoptosis].

PMID- 9610179
TI  - [Induction of manganese superoxide dismutase gene expression in broncho
      epithelial cells after exposure to mineral wool].

PMID- 9610180
TI  - [Cellular association of antiproteases].

PMID- 9610181
TI  - [Cell activation and cytokine liberation in pulmonary sarcoidosis--immunologic
      analysis and clinical relevance].

PMID- 9610182
TI  - [Sense of smell in allergic rhinitis].
AB  - BACKGROUND: Olfactory dysfunction is one of the major complaints in patients
      suffering from allergic rhinitis. Little is known about the onset of hyposmia in
      seasonal allergy. METHODS: We performed two prospective studies to examine
      olfactory function in allergic rhinitis using an established (modified CCCRC)
      test for olfactory threshold, identification and discrimination. RESULTS: In a
      pilot study the time-course of olfactory function in 14 patients with allergic
      rhinitis to grass pollen was examined at the beginning of the season. Olfactory
      function was evaluated birhinal on day 3, 7, 14, and 21 of the season.
      Preseasonally, all patients were normosmic. There was a significant decrease in
      threshold and identification between the third and fourteenth day of the season,
      resulting in a moderate hyposmia in the mean. Hyposmia was not correlated to
      subjective symptom of nasal blockage. Therefore, a follow-up study was performed
      on 17 patients and a control group with a similar study design including
      measurements of nasal volume flow (rhinomanometry) and an inflammatory cell
      activation marker (ECP) in nasal secretions. The time-course of the olfactory
      changes was much better correlated to the inflammatory measure than to nasal
      volume flow. CONCLUSIONS: Patients with allergic rhinitis develop a significant
      olfactory dysfunction under allergen exposition. Inflammatory dysfunction of the
      olfactory epithelium seems to be more important than respiratory dysfunction in
      the pathomechanism of allergic hyposmia.

PMID- 9610183
TI  - [Activated eosinophilic granulocytes in wheezing infants indicate chronic airway
      obstruction].

PMID- 9610184
TI  - [Sensitization to storage mites--studies of the incidence of sensitivity to
      storage mites in comparison with house dust mites. Experiences in allergologic
      ambulatory care].
AB  - We examined the prevalence of sensitisation to storage mites and house dust mites
      in patients attending a pneumologist and allergologist in the office and clinical
      outpatient department. Our findings show sensitisations to storage mites up to
      12%, to house dust mites in 26%. From a total of 3213 patients 914 patients (=
      28%) showed positive skin reactions against at least one storage mite. There is a
      relationship of about 2:1 between house dust mites and storage mites in skin test
      results. From these data, safe conclusions as to the prevalence of storage mite
      sensitisation among the general population may not be drawn.

PMID- 9610185
TI  - [Sensitization in budgerigar owners].
AB  - In a prospective study 258 adults were investigated for sensitisation against
      bird antigens (budgerigar, canary, pigeon) using intracutaneous test. 18 of 78
      budgerigar keepers were sensitised against budgerigar feathers. 30 (38%) showed a
      positive skin reaction at least with one of the three extracts tested. In none
      bird exposed persons a sensitisation was found in 18/96 (19%) against budgerigar
      and in 24/96 (25%) against at least one of the three allergen extracts. Late
      reactions occurred in 5/70 (7%) budgerigar keepers, 4/5 with pigeon feathers. The
      frequency of sensitisation against budgerigar antigens increased to 48% of bird
      keepers (24/50) if the birds could fly in their homes instead of being caged
      always (4/22, 18%). Three of the 78 budgerigar keepers (4%) had a positive nasal
      provocation with feathers extract, they were skin positive against all three bird
      antigens tested.

PMID- 9610186
TI  - [Guidelines for bronchial provocation tests with pharmacologic agents. "Bronchial
      Provocation Tests" Study Group].

PMID- 9610187
TI  - [German Society of Pneumology: recommendations for carrying out and evaluating
      stress tests in pneumology. Cardiorespiratory Interaction Section of the German
      Society of Pneumology].

PMID- 9610188
TI  - [Prevention and therapy of bronchial infections. Recommendations of the German
      Respiratory League of the German Society of Pneumology].

PMID- 9610212
TI  - The usefulness of the Functional Status Questionnaire and Medical Outcomes Study
      Short Form in Parkinson's disease research.
AB  - Parkinson's disease (PD) has no cure and is a progressive neurological disorder
      with treatment aimed at the maintenance of function and limitation of the
      symptoms. No extensive studies of the disease's impact on health-related quality
      of life (HRQoL) have been conducted. The purpose of this study was to assess the
      potential usefulness of the Medical Outcomes Study Short Form (SF-36) and the
      Functional Status Questionnaire (FSQ) in Parkinson's disease research. This cross
      sectional study of 193 PD patients who visited two hospital-based neurology
      clinics used self-administered in-clinic and take-home questionnaires to
      ascertain the demographic and environmental characteristics of the subjects and
      to gain health profile measures from the SF-36 and the FSQ. The two health
      profiles provide important HRQoL information supplementary to the traditional
      signs and symptoms evaluated by the Unified Parkinson's Disease Rating Scale
      (UPDRS). Many of the HRQoL measures discriminate progressive stages of disease in
      this study group and distinguish those with complications of therapy from
      subjects without complications.

PMID- 9610213
TI  - The European Organization for Research and Treatment of Cancer approach to
      developing questionnaire modules: an update and overview. EORTC Quality of Life
      Study Group.
AB  - The European Organization for Research and Treatment of Cancer (EORTC) Quality of
      Life Study Group has adopted a modular approach to quality of life (QoL)
      assessment in cancer clinical trials. The core instrument (the EORTC QLQ-C30)
      covers a range of QoL issues relevant to a broad spectrum of patients with
      cancer. The QLQ-C30 is designed to be supplemented by more specific subscales
      ('modules') to assess aspects of QoL of particular importance to specific
      subgroups of patients. Since individual members of the study group were to be
      involved in module development, guidelines were established. The primary aim of
      these guidelines was to standardize the module development process in order to
      ensure uniformly high quality across modules. This paper gives an update of the
      work completed to date. First, while the guidelines proved practical for module
      development, producing modules that exhibit adequate levels of psychometric and
      cross-cultural validity, experience pointed to three areas where the guidelines
      required more precision. These amendments will be provided and include (1)
      stricter monitoring of the developmental process from within the study group, (2)
      the explicit requirement of involvement of the study group and (3) a more precise
      definition of the criteria to be fulfilled before modules are allowed to be
      called 'EORTC modules'. Second, an overview of the modules currently under
      development or available for general use is provided. These modules include those
      for body image, high-dose chemotherapy, leukaemia, myeloma, palliative care and
      the following cancers: bladder, brain, breast, colorectal, head and neck, lung,
      oesophageal, ophthalmic, ovarian, pancreas and prostate. Finally, the need for
      the coordination of efforts in module development, both from within and outside
      the EORTC, is discussed.

PMID- 9610214
TI  - Measurement of fatigue in cancer patients: development and validation of the
      Fatigue Symptom Inventory.
AB  - Although fatigue is one of the most common and debilitating symptoms experienced
      by cancer patients, it has received little systematic attention. This situation
      is due in large part to the lack of adequate instruments to measure fatigue. The
      primary aim of this study was to validate a newly developed measure of fatigue
      for use with cancer patients: the Fatigue Symptom Inventory (FSI). This 13 item
      self-report measure was designed to measure the intensity and duration of fatigue
      and its impact on quality of life. The psychometric properties of the FSI were
      assessed in women undergoing treatment for breast cancer, women who had completed
      treatment for breast cancer and women with no history of cancer. A seven-item
      interference subscale was found to have good internal consistency, with alpha
      coefficients above 0.90 in all three groups. The complete FSI was found to have
      rather weak to moderate test-retest reliability among patients in active
      treatment and healthy comparison subjects assessed on three separate occasions.
      Convergent validity was demonstrated using comparisons with existing measures of
      fatigue. Construct validity was demonstrated using comparisons between and within
      groups as well as comparisons with measures of anxiety and depression. Overall,
      the FSI was established as a valid and reliable measure of fatigue in cancer
      patients and healthy individuals. Suggestions are made for the potential
      application of the measure in clinical research.

PMID- 9610215
TI  - Using the EuroQoI 5-D in the Catalan general population: feasibility and
      construct validity.
AB  - Spanish and Catalan versions of the EuroQoi 5-D (EQ-5D) were included in the
      Catalan Health Interview Survey (CHIS) and administered to a randomly selected
      cross-section of 12,245 individuals from the Catalan general population. This
      paper analyses the feasibility, convergent validity and construct validity of
      three parts of the EQ-5D (the descriptive system, the visual analogue scale (VAS)
      and the Spanish tariff) using the results obtained in the CHIS. The feasibility
      was assessed by the number of missing responses. The convergent validity was
      based on the correlations between the EQ-5D scores and the scores on the General
      Health Questionnaire (GHQ) and on an index of self-perceived overall health. The
      construct validity was assessed by analysing the degree to which lower scores on
      the EQ-5D correlated positively with increasing age, being female, being in a
      lower social class or having a lower level of education and with increasing
      levels of disability, co-morbidity, restricted activity, mental health problems
      and poor self-perceived health. A low number of missing responses on the
      descriptive system and the VAS (1.5%) indicated a high level of acceptance. A
      marked ceiling effect was found, with 67% of the sample reporting no problem in
      any EQ dimension. The convergent validity with the GHQ was generally low, though
      moderate on the mood dimension. Self-perceived overall health correlated
      moderately to strongly with the mean VAS and tariff values. The positive
      correlations between lower scores on all three elements of the EQ-5D and
      increasing age, increasing levels of disability, comorbidity, restricted
      activity, mental health problems and poor self-perceived health provide some
      evidence of the instrument's construct validity, as does the fact that women
      reported more problems than men. Multivariate analyses using the VAS and tariff
      values as dependent variables and all of the sociodemographic and health
      variables as independent variables reached R2 values of 0.45 and 0.81,
      respectively. The Spanish and Catalan versions of the EQ-5D have proved to be
      feasible and valid for use in health interview surveys.

PMID- 9610216
TI  - A model of equivalence in the cultural adaptation of HRQoL instruments: the
      universalist approach.
AB  - The health-related quality of life (HRQoL) literature presents a confused picture
      of what 'equivalence' in the cross-cultural use of HRQoL questionnaires means and
      how it can be assessed. Much of this confusion can be attributed to the
      'absolutist' approach to the cross-cultural adaptation of HRQoL questionnaires.
      The purpose of this paper is to provide a model of equivalence from a
      universalist perspective and to link this to the translation and adaptation of
      HRQoL questionnaires. The model evolved from reviews of the HRQoL and other
      literatures, interviews and discussions with researchers working in HRQoL and
      related areas and practical experience in the adaptation and development of HRQoL
      instruments. The model incorporates six key types of equivalence. For each type
      of equivalence the paper provides a definition, proposes various strategies for
      examining whether and how types of equivalence can be achieved, illustrates the
      relationships between them and suggests the order in which they should be tested.
      The principal conclusions are: (1) that a universalist approach to the cross
      cultural adaptation of HRQoL instruments requires that six types of equivalence
      be taken into account; (2) that these are sufficient to describe and explain the
      nature of the cross-cultural adaptation process; (3) that this approach requires
      careful qualitative research in target cultures, particularly in the assessment
      of conceptual equivalence; and (4) that this qualitative work will provide
      information which will be fundamental in deciding whether to adapt an existing
      instrument and which instrument to adapt. It should also result in a more
      sensitive adaptation of existing instruments and provide valuable information for
      interpreting the results obtained using HRQoL instruments in the target culture.

PMID- 9610217
TI  - The quality of life of older adults with urinary incontinence: determining
      generic and condition-specific predictors.
AB  - Urinary incontinence (UI) is an unpleasant problem for many adults. This study
      determined the importance of demographic, health and incontinence variables for
      the generic and incontinence-specific quality of life (QoL) of older adults (age
      > or = 60 years). Telephone surveys of adults reporting at least weekly episodes
      of UI (n = 435) were conducted as part of a randomized, controlled trial.
      Logistic regression analyses showed that the predictors of generic and
      incontinence-specific QoL differed. Life satisfaction, a generic outcome, was
      predicted by education, the number of days in bed due to health problems, the
      number of days not feeling well and the amount of urine lost. Generic health was
      related to education, the number of days sick in the previous 30 days and the
      number of days health issues restricted activities. The incontinence-specific QoL
      outcomes were predicted by age, mobility difficulties, the amount of urine lost,
      the frequency of UI, and the number of daytime and night-time voids. The specific
      QoL measures provide a different profile of those most affected in this sample
      than that obtained by the generic measures. The most affected are younger persons
      with severe urine loss. Older persons may have other conditions impinging on QoL
      and may have adapted behaviourally and psychologically to urine loss.

PMID- 9610218
TI  - The psychosocial health status of carers of persons with dementia: a comparison
      with the chronically ill.
AB  - This project aimed to determine overall psychosocial health (measured using the
      psychosocial dimension of the Functional Limitations Profile) and factors which
      influence this in a group of carers of those with dementia and to compare their
      psychosocial health with that of older people attending general practitioners
      (GPs); arthritis support groups and a pain clinic (out-patients) and a group of
      community dwellers undergoing renal dialysis. The carer group showed a
      significant decrease in recreation and pastimes and social interactions compared
      to older GP attenders. The carers showed similar restrictions in social
      interactions and recreation to those with chronic arthritis, but the latter were
      more impaired in the domains of emotional behaviour and sleep and rest. The older
      people attending a pain clinic did not differ in the areas of alertness and
      social interactions compared to the carer group. The dialysis group demonstrated
      the greatest dysfunction overall. These results suggest that the psychosocial
      health of carers of those with dementia is impaired, the profile of which differs
      from those suffering with chronic diseases. Social and recreation activities
      appear most affected in the carers. Commensurate with studies exploring the
      health status of those suffering from diseases, the measurement of the
      psychosocial health status of carers should also be considered in the scope of
      assessment and intervention.

PMID- 9610220
TI  - Quality of life issues in patients with diabetes and lower extremity ulcers:
      patients and care givers.
AB  - The impact of lower extremity ulcers on the quality of life (QoL) of patients
      with diabetes and their care givers was assessed in a series of focus groups.
      Fourteen patients with diabetes and lower extremity ulcers and 11 care givers
      participated in the focus groups. Semi-structured discussions identified the
      issues relating to four broad QoL domains and subdomains: social (daily, leisure,
      family and social life), psychological (emotional health and positive
      consequences), physical (physical health and treatment impact) and economic
      (employment and finances). The patients and care givers experienced a negative
      impact on all domains of QoL because of the limitations in mobility caused by the
      ulcer which required an adaptation to a different lifestyle. A reduction in
      social activities, increased family tensions, lost time from work and a negative
      impact on general health were experienced by both groups. It is necessary to
      separate the impact of the ulcer from the general condition of diabetes on both
      patients' and care givers' QoL. The results from this disease-specific focus will
      allow for an improved clinical understanding with targeted interventions and
      contribute to the development of a disease-specific instrument to understand and
      measure QoL better in these individuals.

PMID- 9610219
TI  - Adaptation and evaluation of the Liverpool Seizure Severity Scale and Liverpool
      Quality of Life battery for American epilepsy patients.
AB  - The Liverpool Seizure Severity Scale (LSSS) and the Liverpool Quality of Life
      (LQOL) battery were developed in Great Britain to assess the severity of seizure
      symptoms and the impact of epilepsy on patients' quality of life. The scales have
      been validated on British patients, but have not been validated for use with
      American patients. The objectives of this study were to adapt the scales to the
      American population and to evaluate their reliability and validity. After
      modifications recommended by focus groups with patients and epilepsy specialists,
      the scales were administered to a sample of 90 epilepsy patients who had
      experienced seizures within the previous 4 weeks. Comparisons of patients with
      generalized tonic-clonic seizures (n = 58) and partial seizures (n = 32) revealed
      significant differences on 12 of the 20 items on the LSSS as well as the total
      score. None of the six LQOL subscales (negative drug effects, positive drug
      effects, affect balance, sense of mastery, life fulfillment and impact of
      epilepsy) distinguished patients with different seizure types but five of the six
      subscales were significantly correlated with seizure severity. The internal
      consistency and test-retest reliability were adequate for both the LSSS and LQOL.
      Finally, five of the six LQOL scales were significantly correlated with
      independent measures of mental health, physical health and role functioning.

PMID- 9610221
TI  - [Exercise and sports: an undervalued health resource].
AB  - The importance of physical activity for health is internationally recognised. The
      physiological and the epidemiological evidence for health effects of both
      moderate and vigorous intensity exercise is demonstrated and a "Physical Activity
      Pyramid" is recommended: Half an hour of moderate intensity activities a day at
      the base level are already promising substantial health effects. On the second
      step, additional benefits can be derived from cardiorespiratory fitness training,
      strength training and stretching exercises. The top of the pyramid can be reached
      by further sports activities.

PMID- 9610222
TI  - [Sudden cardiac death in sports].
AB  - The majority of sudden deaths during physical activity is due to cardiac
      diseases. In younger persons (< 25 years) the hypertrophic cardiomyopathy is most
      often involved, followed by infectious cardiac diseases (myocarditis). Already in
      persons up to 40 years the incidence of coronary arteriosclerosis markedly
      increases. Although the acute risk of sudden cardiac death is enhanced during
      sport activity, regular physical training results in an overall cardioprotective
      effect. Demands on the sports medical examination are discussed in the light of
      the prevention of sudden cardiac death as well as the long-term health care.
      Based on a careful anamnesis and clinical examination the ECG as well as the
      echocardiography present non-invasive methods with high informational value. An
      exercise-ECG is especially recommended to evaluate the eligibility for physical
      exercise in persons > 35-40 years and in subjects with risk factors for
      cardiovascular diseases.

PMID- 9610223
TI  - [Sports in the heart rehabilitation group--experiences with ambulatory
      rehabilitation at home].
AB  - Regular physical exercise has shown to be beneficial for patients with
      cardiovascular disease. Therefore cardiac rehabilitation in Germany is continued
      for years after hospital discharge in outpatient cardiac exercise groups which
      meet twice a week under the guidance of a physician and a sports instructor.
      Before participation cardiac patients have to be examined including exercise
      tests and echocardiography for assessment of contraindications for exercise
      therapy as well as individual exercise capacity. Patients are assigned to two
      groups with different levels of exercise intensity according to their symptom
      free work-capacity (cutoff level 1 W/kg). During exercise sessions sports
      specific forms of exercise such as stretching, aerobic exercise or ball games are
      accompanied by psychosocial elements such as stress management. This global
      approach is intended to improve cardiovascular risk factors, cardiac function,
      and work capacity as well as to stabilize the patient psychologically in order to
      accelerate social integration. Recently these groups have opened towards patients
      after cardiac transplantation or with severe heart failure. Therefore, cardiac
      exercise groups play a central role in cardiac rehabilitation long after the
      acute cardiac event.

PMID- 9610224
TI  - [Recommendations for sports in chronic obstructive pneumopathy (COPD)].
AB  - Although exercise tolerance can be quite limited in patients with COPD due to
      dyspnea, arterial desaturation, chronic disuse muscular atrophy, and fear of
      distressing symptoms, regular daily exercise is an important part of optimal
      disease management. Patients can be provided with simple exercise instructions
      tailored to their physiological impairment and recreational interests. The
      benefits of regular exercise observed even in the most severely obstructed
      patients include desensitization to dyspnea, increased exercise tolerance,
      improved capacity for daily activities, greater self esteem and independence, and
      reduced rates of hospitalization. These benefits of exercise training in COPD are
      best realized within a multidisciplinary program of supervised pulmonary
      rehabilitation, that also incorporates education about COPD, proper use of
      medications and oxygen, and psychosocial counseling.

PMID- 9610225
TI  - [Diagnosis of performance capacity and guided training for physical endurance].
AB  - The evaluation of the aerobic capacity is of great importance for athletes as
      well as for patients with cardiac and pulmonary diseases. For objective
      measurements of cardiorespiratory and metabolic responses heart rate, lactate
      concentration in capillary blood and ventilatory gas exchange are determined
      during incremental exercise tests either on different ergometers in a laboratory
      or under training conditions in the field. Besides the maximal O2-uptake (VO2max)
      several ventilatory and lactate thresholds have been proposed as reliable values
      for assessing the aerobic capacity and giving training recommendations. For
      interpretation of the results the training and nutrional behaviour in the
      previous days have to be considered as especially the lactat thresholds are
      influenced by the glycogen content of the muscles. Furthermore, training
      recommendations cannot always be easily transferred from test to training
      conditions as these can be very different from each other.

PMID- 9610226
TI  - [Pseudo-anemia caused by sports].
AB  - Regular physical training leads to an increase of plasma volume by 10-20 percent.
      Therefore, hemoglobin concentration slightly below normal values in the presence
      of low-normal serum ferritin levels in athletes are usually due to a dilutional
      "pseudoanemia". Several cross sectional studies indicate that true iron
      deficiency anemia is not more frequent in athletes than in the general
      population. Since regular physical activity, especially extensive, running
      increases iron loss, mild iron deficiency (abnormal serum ferritin and normal
      hemoglobin concentration) and sometimes true iron deficiency anemia can occur
      especially when nutritional iron intake is insufficient and iron demand is
      increased because of growth (children, adolescents) or additional iron loss
      (menstruation). Several controlled studies indicate that iron supplementation
      (recommended dose 2 x 100 mg elementary iron/day) improves performance only when
      hemoglobin concentration increases, i.e. when iron deficiency anemia is present.
      On the contrary, iron supplementation has no measurable effects on performance
      when hemoglobin concentration cannot be increased, i.e. in mild iron deficiency.

PMID- 9610227
TI  - [Menstrual disorders in athletes].
AB  - It is important to pay attention to bone metabolism in women long before the
      menopause. Irregular menstruation with anovulatory cycles or amenorrhoea
      persisting over several years have negative effects on bone formation and total
      bone mass already within a few years after menarche. They lead to a lack of
      oestradiol and are often associated with inadequate and unbalanced nutrition
      (e.g. lack of calcium and proteins). This results in severe impairment of bone
      formation and a net loss of bone mass. It is the duty of the doctors taking care
      of female athletes (as well as non-athletes) with irregular menstrual cycles or
      amenorrhoea to protect them against osteoporosis which may manifest itself 2-5
      decades later. In the special case of female athletes a reduced bone mass is an
      important risk factor for stress fractures which can result in interruption or
      even in a premature termination of promising athletic careers. Athletes with
      retarded menarche, irregular menstrual cycles, or amenorrhoea must, therefore, be
      referred to a gynecologist for further diagnosis and treatment.

PMID- 9610228
TI  - [Overuse syndrome of the soft tissues of the lower extremity].
AB  - Sports activities with high demands and stresses to the musculoskeletal system
      increase the risk of overuse injures. The etiologic mechanisms are
      multifactorial, with both intrinsic and extrinsic factors. In spite of better
      diagnostic equipment and conservative methods of treatment, some of these overuse
      injuries do not heal and a structural damage of the tissue remains. Thus, surgery
      is often the only way to relieve the symptoms and to restore normal function.
      This article provides a basic overview of the epidemiology, anatomy,
      biomechanical factors, stress responses and therapeutic principles regarding
      overuse injuries of the soft tissues.

PMID- 9610229
TI  - [Stretching--possibilities and limits].
AB  - The basic scientific knowledge about stretching remains incomplete in spite of
      its wide use in sports and physiotherapy. This article deals with the assessment
      of the flexibility and with the anatomical and physiological basis and
      limitations of stretching. The effects of stretching on delayed onset muscle
      soreness (DOMS), performance and regeneration are discussed. Recommendations are
      given for stretching as a measure of warming-up and cooling-down, for stretching
      before exercises, which demand explosive maximum muscle strength, and for
      stretching after training for strength endurance.

PMID- 9610230
TI  - [Inhaled glucocorticosteroids--distribution, stability, therapy].
AB  - In this paper the basic methods of aerosol generation--ultrasonic and pneumatic
      and problems resulting from their use have been discussed. Nebulisation of the
      inhaled steroids has been presented together with metered dose inhalers (MDI) and
      dry powder inhalers (DPI). Special attention has been payed to the role of lung
      volume chambers (spacers). In the tables the review of steroid preparations and
      their dosage has been displayed.

PMID- 9610231
TI  - [Longterm effects of steroid therapy].
AB  - Asthma is a chronic inflammatory disease of the airways play. Anti-inflammatory
      drugs the fundamental role in the treatment of asthma and among them steroids are
      the most important. However, oral steroids may cause many serious side effects. A
      major breakthrough in the treatment of asthma was introducing inhaled steroids.
      Inhaled steroids have much less side effects than oral steroids, although they
      have the same anti-inflammatory activity. Long term effect of inhaled steroids
      can be divided into wanted and unwanted outcome. The desirable anti-inflammatory
      effect of steroids is reflected by lowering of bronchial hyperresponsiveness and
      a better control of asthma symptoms. Inhaled corticosteroid may have systemic
      side effects similar to those observed with oral steroids such as 1) adrenal
      suppression, 2) effect on bone metabolism, 3) growth suppression in children, 4)
      impaired skin collagen synthesis, 5) cataract, 6) metabolic disturbances, 7)
      effect on central nervous system. Topical side effects of inhaled corticosteroid
      such as oral candidiasis, dysphonia and cough effect about 10 to 30% of patients
      taking those drugs. Summing up it is advisable to use inhaled corticosteroid in
      the lower effective dose.

PMID- 9610232
TI  - [The role of steroid therapy in treatment of bronchial asthma in children].
AB  - Bronchial asthma is a chronic inflammatory disease of respiratory system.
      Antiinflammatory therapy, especially inhaled steroid is a basic form of
      pharmacotherapy. Inhaled steroids are used in chronic mild, medium and severe
      bronchial asthma. Dose of drugs depends on severity of the illness.

PMID- 9610233
TI  - [Mechanism of action for corticosteroids].
AB  - The article is the review of the literature data concerning the molecular
      mechanism of action of corticosteroids in bronchial asthma and related diseases.
      Extensive research has led to the detailed understanding of the mechanisms
      underlying the cellular actions of steroids, their interactions with beta 2
      agonists and reasons of steroid resistance.

PMID- 9610234
TI  - What health for whom? A challenge for epidemiology.
AB  - The ideal of universal access to the best possible health is being replaced by
      questions of how best to distribute limited health resources. Epidemiology can
      help to answer these questions by combining its functions of investigation and
      target-setting. Thus studies on health differences should be aimed at reducing
      unjust inequalities.

PMID- 9610235
TI  - Validation of indicators for health policy research.
AB  - The information used to determine the subjects of health policy research takes
      the form of indicators obtained by data manipulation. Validation is the process
      whereby the ability of health indicators to measure what they are supposed to
      measure is determined. The author discusses ways of overcoming various
      limitations affecting the development of health indicators.

PMID- 9610237
TI  - Knowledge-based technology in the service of health.
AB  - The significance of numerical information for decision-making usually has to be
      assessed on the basis of knowledge that does not readily lend itself to
      quantification. Computational logic can help to handle the complexity of this
      process of interpretation without sacrificing the necessary rigour. When this
      approach is used, health indicators are expressed in the form of a "knowledge
      map".

PMID- 9610236
TI  - Information and research for decision-makers.

PMID- 9610238
TI  - WHO at fifty. Highlights of the early years until 1960.
AB  - To mark the fiftieth anniversary of the World Health Organization in 1998, World
      Health Forum briefly reviews the early years of the Organization and highlights
      some of the wide range of activities carried out or promoted by WHO during the
      last 50 years. This article describes the founding of the Organization and gives
      examples of WHO's work until 1960.

PMID- 9610239
TI  - Getting together for injury control.
AB  - The proceedings of a round table session on injury control in Africa, held as
      part of the Third International Conference on Injury Prevention and Control, are
      outlined in the present article. The prospects for collaborative efforts in this
      field seem reasonable, but increased support from governments and the
      international donor community is essential if the immense burden of injury is to
      be significantly diminished.

PMID- 9610240
TI  - Help for people with disabilities: do cultural differences matter?
AB  - Since the Year of the Disabled (1981) and the Decade for Disabled Persons (1983
      1992), many questions have arisen about how to understand and deal with
      disability in a multicultural world. To what extent can programmes developed in
      one place be successfully implemented elsewhere? What kinds of cultural and
      social differences matter and how can they be taken into account?

PMID- 9610241
TI  - Best resource use for disabled children.

PMID- 9610242
TI  - Prevention of blindness--WHO's mission for vision.
AB  - Changes in the world order and in technology during the last half-century have
      revolutionized approaches to blindness prevention and sight restoration. Although
      the possibilities have improved and increased immeasurably, unnecessary blindness
      will remain common, especially among the poor, unless a concerted international
      effort is made to prevent it.

PMID- 9610243
TI  - Occupational health--a requirement for development.
AB  - Many people are at serious risk of ill-health and accidents because of the
      conditions they encounter in their workplaces. Combating these dangers requires a
      multidisciplinary approach and special attention to the elimination of hazards
      from the work environment. This is a long-standing concern of WHO.

PMID- 9610244
TI  - WHO's laboratory programme.
AB  - The dependence of modern medicine on laboratory services has increased enormously
      during the last 50 years. Rapid developments in this field present a challenge
      for standard setting and quality control.

PMID- 9610245
TI  - Community participation--with provider collaboration.

PMID- 9610246
TI  - Male involvement in family planning in Turkey.
AB  - Many men in Turkey are motivated to use contraception and to share responsibility
      for family planning with their wives. About half the couples practising family
      planning use male-dependent methods. Men commonly use traditional methods,
      predominantly withdrawal, and should be treated as a specific target group in
      family planning programmes in order to motivate them to use modern methods.

PMID- 9610247
TI  - Alma-Ata and after.
AB  - The Alma-Ata Conference on Primary Health Care in 1978 marked a turning point in
      WHO's history and in international cooperation in health. Attempts to put the
      decisions of that conference into practice have not always been successful, but
      the principles that were formulated then remain as valid as ever. The author, who
      was one of the main moving spirits behind this unique event, puts things into
      perspective.

PMID- 9610248
TI  - WHO--from the past to the future.

PMID- 9610249
TI  - Community participation: continuing the momentum.

PMID- 9610250
TI  - On auscultation.

PMID- 9610251
TI  - Memories of a WHO expert in midwifery.
AB  - Much of the health infrastructure we now take for granted is the result of
      determined efforts made in the 1960s and 1970s. The objective was relatively
      clear: to help build up strong national health systems. But to do that an
      uncommon amount of energy and imagination was needed.

PMID- 9610252
TI  - The rights of the patient in art therapy.
AB  - Artistic activities are widely used in mental health care for both diagnostic and
      therapeutic purposes. The art produced in this process is often recognized as a
      valuable commodity in its own right, and this raises questions of ownership, self
      determination, privacy, respect and psychic integrity.

PMID- 9610254
TI  - Obesity is major public health problem.

PMID- 9610253
TI  - Global campaign against epilepsy.

PMID- 9610255
TI  - Managing childhood illnesses.

PMID- 9610256
TI  - The patient connection.

PMID- 9610257
TI  - Latex allergies.

PMID- 9610258
TI  - Recommendations for routine immunizations of oral health care providers.

PMID- 9610259
TI  - Universal precautions reconsidered.

PMID- 9610260
TI  - Oral cancer examination guide. Hines Tumor Registry, Hines VA Medical Center.

PMID- 9610261
TI  - 8 tips on increasing practice productivity.

PMID- 9610262
TI  - Sealants.

PMID- 9610263
TI  - Vaccine. Preventable diseases. Recommendations for routine immunizations in oral
      health care providers.

PMID- 9610264
TI  - Treating after hours emergency patients.

PMID- 9610265
TI  - Air abrasion in dentistry.

PMID- 9610266
TI  - Polishing your image.
AB  - Today, dental assistants are becoming more aware that a professional image is
      necessary for putting dental professionals in the best light in the changing
      health care society. Not only must dental assistants know how to work in the
      system and how to effectively care for dental patients, but attention to matters
      such as personal grooming, dress, and body language is necessary if dental
      assistants are to be a powerful and proud profession in today's society. How you
      look and act will make a difference in how others treat you. When you act like a
      professional, others will react to you as one.

PMID- 9610267
TI  - Are we dental assistants marketing and promoting our practices?

PMID- 9610268
TI  - Managing the pregnant dental patient.

PMID- 9610269
TI  - Folic acid update.

PMID- 9610270
TI  - Dysmorphophobia: a case successfully treated using a multidisciplinary approach.
AB  - Dysmorphophobia is a syndrome in which a person of normal appearance becomes
      obsessed with an aspect of their appearance which they feel is noticeably
      defective, and for which they constantly seek treatment. This case report
      describes the successful management of a young woman with dysmorphophobia using a
      multidisciplinary approach.

PMID- 9610271
TI  - Restoration of posterior teeth with composite resin. 1: Direct-placement
      composite.
AB  - Composite restorative materials were introduced to the dental profession in the
      early 1960s and quickly became the principal anterior restorative material.
      Following improvements in composite technology, these materials were also
      developed as aesthetic posterior materials but were initially hampered by
      problems of poor wear resistance. In this, the first of two articles on the uses
      of composite replacement materials, the development of composite resins are
      discussed and the problems of using direct-placement composite to restore
      posterior teeth are examined in detail. The second article will review the use of
      the composite inlay technique.

PMID- 9610272
TI  - Large pyogenic granuloma: a case report.
AB  - Pyogenic granuloma is a common reactive lesion seen in the third decade of life,
      generally between 1 and 2 cm in size. It may be confused clinically with
      malignancy. It is treated by surgical excision, and recurrence is rare.

PMID- 9610273
TI  - Belle Maudsley Lecture. Digits, dummies and malocclusions.
AB  - When considering the aetiology of malocclusion in general, factors are often
      cited as having a genetic basis or an environmental basis. An individual
      malocclusion is likely to be a result of the variable effects of multiple
      environmental influences, upon an equally variable genetic predisposition. One of
      the most tangible 'environmental' factors is that of sucking habits involving
      digits or dummies. This review considers the nature of these habits, their
      effects on the developing dentition and methods used to combat the problem.

PMID- 9610274
TI  - Squamous cell carcinoma of the gingiva in an HIV-positive patient: a case report.
AB  - This article presents a case of gingival squamous cell carcinoma in a patient who
      was HIV positive but who had no history of pan chewing, smoking, alcohol
      consumption or nutritional deficiency. Investigations also revealed the presence
      of superimposed pseudomembranous candidiasis. The case reported reveals that
      squamous cell carcinoma of the gingiva may occur as an oral manifestation of
      AIDS.

PMID- 9610275
TI  - Trouble-free debonding in orthodontics: 2.

PMID- 9610276
TI  - Case report: radical management of an adolescent with amelogenesis imperfecta.
AB  - Amelogenesis imperfecta is a rare developmental abnormality of enamel, the main
      clinical problems of which are extensive loss of tooth tissue, poor aesthetics
      and tooth sensitivity. Management often involves complex and long-term treatment
      but is usually successful if patients are well motivated. This case report
      outlines the management of a teenager with amelogenesis imperfecta (hypocalcified
      type) who had requested a dental clearance at an early age.

PMID- 9610277
TI  - A cephalometric analysis of six Twin Block patients. A study of mandibular (body
      and ramus) growth and development.
AB  - A study of the effect of the Twin Block appliance on the underdeveloped mandible.
      Significant growth has been measured cephalometrically and charted on 6 patients,
      4 males and 2 females, who have worn the Twin Block for approximately one year.
      With Pre-Twin Block cephalometric taken, the Twin Block was inserted and bite
      blocks were advanced approximately every 8 weeks. Progress and Post-Twin Block
      cephalometric (lateral) radiographs show a significant increase in ramus height
      and mandibular body length. The purpose of this article is to demonstrate actual
      mandibular bone growth. A number of the subjects still are in the process of
      finishing their fixed bracketing phase, and we hope to follow this article with
      another, demonstrating post Twin Block occlusion and other case finishing
      factors.

PMID- 9610278
TI  - Eagle's syndrome and the trauma patient. Significance of an elongated styloid
      process and/or ossified stylohyoid ligament.
AB  - The elongated styloid process has been noted in medical literature for hundreds
      of years and is commonly referred to as Eagle's Syndrome. The presence of
      anomalous structures is always a concern to therapists and surgeons. The anatomy,
      embryology, etiology, plus treatment risks are reviewed. The affects of
      hyperflexion/hyperextension (whiplash) injuries are exacerbated in the presence
      of this unexpected calcified structure. The clinical significance of Eagle's
      Syndrome in the treatment of the trauma patient is explored.

PMID- 9610279
TI  - Remodeling of the temporomandibular joint condyle. Following direct trauma to the
      mandible.
AB  - A patient involved in a bicycle accident received direct trauma to the mandible
      and the maxillary anterior teeth. The injuries were demonstrated using x-rays,
      tomography and magnetic resonance imaging (MRI).

PMID- 9610280
TI  - Facial asymmetry: recognition of TMD.
AB  - For many years researchers and clinicians have been aware of the varying
      presenting signs and symptoms common in the TMD patient. The symptom-complex
      frequently includes preauricular pain; cephalgia (predominantly frontal,
      temporal, occipital, vertex, retro- and periorbital); cervicalgia
      (immobility/stiffness); otalgia (congestion, vertigo, tinnitus). The most
      prominent signs are those of joint sounds (popping, click and crepitus due to
      disc displacement with reduction and/or osseous breakdown); restricted mandibular
      excursion (disc displacement without reduction); and mandibular
      deviation/deflection (disc(s) displacement).

PMID- 9610281
TI  - Relationship between morphologic malocclusion and temporomandibular disorders in
      orthodontic patients prior to treatment.
AB  - The purpose of this study was to investigate the role of malocclusion in
      temporomandibular disorders (TMD) in an orthodontic patient population prior to
      treatment. The subjects were 508 Chinese patients (214 males, 294 females), 6 to
      56 years of age. The type of malocclusion was diagnosed using dental casts, and
      TMD signs were recorded by clinical examination. The overall prevalence of TMD
      signs in the whole group was 26.6%. The frequencies of TMD signs were 44.0% for
      edge-to-edge bite, 31.2% for posterior crossbite, 27.6% for deep bite, 26.5% for
      excessive overjet, 26.5% for crowding, 23.7% for anterior crossbite and 23.6% for
      open bite. Although patients with edge-to-edge bite or posterior crossbite had
      TMD signs more often than the others in the whole group, the differences did not
      reach statistical significance. We did not find a significant relationship
      between morphologic malocclusion and TMD.

PMID- 9610282
TI  - How to complete a medical insurance form.
AB  - The information submitted is knowledge accumulated over years of experience
      teaching dentists how to bill medical insurance. This is supplemented with a good
      number of personal expert witness testimonies in criminal and malpractice
      insurance cases. The objective is to prevent problems before they start with the
      prudent use of information. My experience in court testimony on these issues has
      shown me that there is an army of lawyers, insurance company fraud examiners, and
      dentists working for the aforementioned, just waiting for you to improperly use
      this method of insurance reimbursement. Use this only if you understand the
      nuances of what it is you are doing! For example, any procedure you bill to
      dental insurance using CDT-2 codes can be billed to medical insurance using
      medical insurance CPT-95 codes. The difference is that if the procedure is not a
      covered medical expense, it will not be paid by the medical insurance carrier. I
      strongly suggest that you do not fall into the trap of obfuscating these codes.
      There are a number of so-called insurance "gurus" teaching dentists how to write
      confusing and misleading operative reports so as to obtain reimbursement for
      procedures that normally would not be covered. I beseech you--please do not do
      it! The penalties are severe. You will experience a significant increase in
      payments from the medical insurance when procedures are submitted in the proper
      manner. More and more computerized dental insurance management programs are
      offering their clients the ability to automatically cross-code and submit
      dental/medical insurance claims. It is a recognized ability of dentists to do
      such. Billing responsibly is of the utmost importance.

PMID- 9610283
TI  - An interview with Dr. William Clark. Interview by Craig C. Stoner.

PMID- 9610284
TI  - Higher levels of orthodontic and dental excellence.
AB  - In the past, providers of orthodontic services were solely concerned with
      esthetic/cosmetic considerations of the teeth. In more recent years emphasis has
      been placed on the interdigitation of the teeth in centric occlusion combined
      with the absence of occlusal interferences in sliding/gliding jaw movements with
      the teeth in partial contact with each other (protrusive, cuspid disclusion,
      etc.). Still more recently true jaw function, or, function of the entire
      stomatognathic system, as opposed to the more limited functional movement of the
      teeth as influenced by their inclined planes when in partial occlusion, has come
      to the fore. And rightly so. This necessarily required consideration of the
      health or pathology of the temporomandibular joint/s because some patients could
      open their mouths more than others. Some opened straight up and down, while
      others deflected to the left or right and some made various noises and jerky
      movements. Others opened noiselessly and smoothly and were in moderate to severe
      pain and pointing their finger at the orthodontic provider.

PMID- 9610285
TI  - Non-extraction therapy in maxillary deficiency cases.
AB  - Combined orthodontic and surgical management of maxillary deficiency with a Class
      III profile has accomplished efficient treatment and predictable results. Also,
      orthodontic/orthopedic therapy can give good results; but, in any case, if one of
      either or a combined therapy is selected, the orthodontist has to be sure of the
      correct diagnosis. The cephalometric analyses have to be done with care as it is
      possible to find contradictions among different analyses, especially in the A/P
      aspect. The Wits appraisal shows good capacity for determining the antero
      posterior maxillomandibular relationship because it is sensitive to the osseous
      dimensional variants and lower anterior facial height. Nevertheless, it is a
      supplementary evaluation requiring additional data for the localization of the
      deformity.

PMID- 9610286
TI  - Management of the airway.
AB  - Management of the airway for sufferers of SDB is the newest field in dentistry
      and is growing at a very rapid rate. An understanding of sleep medicine and
      physiology as well as the techniques for clinically managing the patients is
      necessary and complex. Dentists interested in managing these patients properly
      should consider membership in the SDDS and should pursue continuing education
      through their auspices. This field offers dentists opportunities to participate
      in a tremendously rewarding area of medicine, but requires due diligence to
      participate responsibly in that field.

PMID- 9610287
TI  - The bionator/OCI as a retainer.
AB  - For over a century the complete and long term retention of orthodontic treatment
      results has been the "Achilles heel" of the orthodontic discipline, regardless of
      which particular technique was used to treat a given case nor which treatment
      philosophy spawned its methods. Yes, there are some cases that appear on the
      surface to remain orthodontically stable, preserving the beautiful results
      effected by the treating clinician's efforts without exhibiting even the most
      minuscule post-treatment changes in tooth position.

PMID- 9610288
TI  - Etiological factors and temporomandibular treatment outcomes: the effects of
      trauma and psychological dysfunction.
AB  - This paper examines the effect of trauma and psychological dysfunction as
      etiological factors in temporomandibular disorder (TMD). It employs a thoroughly
      validated measurement system, the TMJ Scale, to determine the effects of
      traumatic temporomandibular joint injury as well as pre-treatment stress and
      psychological dysfunction levels upon presenting symptom levels. It also
      addresses these parameters for the eventual treatment outcome. During the course
      of the study, 754 patients were evaluated at the author's practice, which is
      limited to the diagnosis and Phase I treatment of temporomandibular dysfunction.
      Of those individuals, 693 (91.9%) were found to have clinically treatable
      temporomandibular disorders. At the time of this study, 201 consecutive patients
      (29%) have completed treatment and were deemed to have reached Maximum Medical
      Improvement (MMI). The validated measurement system of the TMJ Scale was
      readministered to this post treatment population. Data analysis revealed that
      trauma patients did not differ from non-trauma patients in initial symptom
      levels, nor in levels of symptom improvement (with the exception of a higher
      palpation pain level reported by the trauma patients). Stress and psychological
      dysfunction were predictive of higher initial symptom perception levels, but were
      not significantly related to treatment outcomes. These findings have important
      implications for practitioners in the field of temporomandibular studies. If it
      can be confirmed that psychological variables have no impact on treatment
      outcome, it would be difficult to justify the now frequently employed "dual axis"
      classifications and major emphasis placed on psychological treatment for
      temporomandibular patients.

PMID- 9610289
TI  - The pen: the clinician's most powerful "handpiece".
AB  - They say when you travel that you have to take 100 photographs per day to
      adequately cover an area such as Disney World, Hawaii, London, or some other such
      place. I thought at first that sounded ridiculous until I tried it myself. They
      were right. If you really try to show the folks back home what your trip to some
      exotic place was really like, about 100 snap shots per day is about what it
      takes. You always seem to wind up with less pictures of things than you think you
      have. The same holds true for record keeping in dentistry. There is no such thing
      as too much.

PMID- 9610290
TI  - The Magill Sagittal and Drive Tube.
AB  - The Magill Sagittal and Drive Tube was developed as a result of the demands for
      more efficient "fixed" functional appliances. Continued pressure on orthodontic
      laboratories and manufacturers has resulted in the development of various 'fixed'
      versions of the appliances necessary to accomplish the goals of functional jaw
      orthopedic therapy. The introduction of 'fixed' functional treatment modalities
      into the traditional "braces correct everything" USA market has spread rapidly
      over the past fifteen years. This method has evolved due to the demand by
      practitioners who want to gain more total control over the patient's treatment.

PMID- 9610291
TI  - Transitional Twin Block.
AB  - When FJO is integrated with fixed orthodontic treatment possibilities are greater
      than with one system only. Given proper case selection and patient corroboration
      consistent results are achieved. The Comfort Twin Block design enhances patient
      acceptance and compliance. Transitional Twin Block Methods to encourage active
      eruption of teeth result in faster case completion. The Twin Block is a versatile
      and effective appliance in the correction of Class II malocclusions.

PMID- 9610292
TI  - Prevalence of hyperactive digastric muscles during swallowing as measured by
      electromyography in patients with myofascial pain dysfunction syndrome.
AB  - One purpose of this clinical study is to establish a relationship between the
      hyper activity of the digastric muscles and predisposition of an individual to
      MPDS (myofacial pain dysfunction syndrome). If a population predisposed to MPD
      could be identified by an early diagnosis, intervention and treatment could
      eliminate potential pain in adulthood. Secondly, can the employment of
      electromyography to aid in the diagnosis of patients with MPD be helpful in
      establishing a program of prevention and treatment? Thirty-one patients, male and
      female, were randomly selected from among those routinely diagnosed as having
      myofascial pain dysfunction syndrome by the dental staff at the Long Island
      Center for Craniofacial Pain. Eighteen patients who did not experience any
      symptoms of facial pain comprised the control group in the study. This study
      demonstrated that the average trace readings which indicate the activity of the
      digastric muscles, as measured by the electromyogram from patients experiencing
      facial pain were significantly higher than those from patients without pain
      symptoms. In every instance, the correlation between facial pain and abnormal
      swallow patterns which are a cause of hyperactivity of the digastrics was
      confirmed.

PMID- 9610293
TI  - Panoramics for the temporomandibular joint?

PMID- 9610294
TI  - Yesterday's dentistry--today's chronic pain. How three seconds of outdated
      technique turned a healthy dentist into a chronic pain patient.

PMID- 9610295
TI  - DORA. Dental Orthogonal Radiographic Analysis: original research.

PMID- 9610296
TI  - Case file #XXX: Jane Doe.

PMID- 9610297
TI  - Fluoride profiles in the cementum and root dentine of human permanent anterior
      teeth extracted from adult residents in a naturally fluoridated and a non
      fluoridated area.
AB  - OBJECTIVES: To determine the effect of water fluoride concentration on the
      fluoride profile across the entire thickness of the cementum and root dentine of
      human permanent anterior teeth in adults. SUBJECTS: Twenty-eight human permanent
      anterior teeth from individuals aged from 30 to over 60 years were studied.
      SETTING: Teeth were obtained from a natural high-fluoride area (West Hartle-pool,
      UK; 1.0-1.3 ppm F in drinking water, WHP) and the other from a non-fluoridated
      naturally low fluoride area (Leeds, UK; 0.1 ppm F in drinking water, LDS).
      DESIGN: Cementum and root dentine were sampled using an abrasive micro-sampling
      technique from the cementum surface to the pulpal surface of root dentine.
      RESULTS: Fluoride concentration was higher in tooth roots (the cementum and
      dentine) taken from the naturally fluoridated area (WHP) than from the non
      fluoridated area (LDS). Age and average fluoride concentration showed a positive
      correlation in WHP dentine, middle region of the root (r = 0.78, P < 0.001) and
      in the apical region of the root (r = 0.61, P < 0.05). WHP cementum had the
      strongest fluoride concentration correlation with age in the cervical region of
      the root (r = 0.67, P < 0.01). An analysis of variance (ANOVA) showed that the
      area (water fluoride content), age and number of years lived in the area combined
      with total age were significant. CONCLUSIONS: The fluoride content of cementum
      and root dentine in adult residents is related to fluoride content in drinking
      water.

PMID- 9610298
TI  - Oral health and history of respiratory tract infection in frail institutionalised
      elders.
AB  - OBJECTIVES: The purpose of this study was to look for a relationship between
      history of respiratory tract infection (RTI) and oral health in very old
      subjects. SETTING AND SUBJECTS: 302 frail elders (mean age: 85 years) living in a
      medical care facility were examined by one dentist. OUTCOME MEASURES: The
      incidence of RTI over 1 year had been recorded along with markers of nutritional
      status and degree of dependency. The oral examination comprised an evaluation of
      hygiene, quality of prostheses and the prevalence of caries, periodontal disease
      and mucosal disorders. RESULTS: One third (33%) of the subjects had experienced
      at least one episode of RTI, and a fifth (19%) had visited the dentist in
      emergency. The incidence of RTI had been greater among dentate subjects and those
      who came to the dentist in emergency. The dentate subjects with a history of RTI
      had higher plaque score (P = 0.02). Half (49%) of the subjects had oral disorders
      that could develop in a dental emergency and these subjects had had a higher risk
      of RTI (relative risk: 1.9, 95% confidence interval: 1.1-3.9). The presence of
      selected oral disorders associated with low serum albumin increased the relative
      risk of having had RTI to 3.2 (1.5-6.7). The association between presence of
      actual oral health problems and previous experience of RTI was more noticeable in
      those who had poor general health or were more debilitated. CONCLUSIONS: The
      present study suggests that poor oral hygiene and the presence of potential
      emergency could be major risk factors for RTI among the frail elderly.

PMID- 9610299
TI  - Oral glucose clearance in nonagenarians in relation to functional capacity,
      medication and oral variables.
AB  - OBJECTIVES: To study oral sugar (glucose) clearance and to examine some factors
      which were believed to either influence or be dependent upon oral glucose
      clearance. DESIGN: Cross-sectional, clinical study with analysis of records.
      SETTING: Goteborg gerontological and geriatric population studies, Goteborg
      University, Sweden. SUBJECTS: 71 community-dwelling individuals, 27 men and 44
      women, of a representative sample of 260 92-year-old persons. INTERVENTION AND
      MAIN OUTCOME MEASURES: Glucose concentration was measured in saliva after chewing
      of a glucose tablet and the clearance was assessed by three different variables:
      (i) the initial salivary glucose concentration, (ii) the area under the curve
      (AUC) and (iii) the clearance time. RESULTS: The glucose clearance showed a wide
      inter-individual variation, which could be explained partly by differences in
      oral state, chewing time, stimulated salivary secretion rate and medication use.
      A positive correlation was found between the clearance variables and the number
      of lactobacilli and mutans streptococci in saliva and the percentage of untreated
      root caries lesions of the total number of exposed root surfaces. CONCLUSIONS: A
      slow oral sugar clearance is more common among 92-year-olds than younger adults
      earlier reported in other studies, particularly in those who have uncompensated
      functional impairments and a high medication history. A decreased oral glucose
      clearance was associated with high counts of salivary lactobacilli and mutans
      streptococci and a high proportion of untreated root caries lesions.

PMID- 9610300
TI  - Staff attitudes to oral health care. A comparative study of registered nurses,
      nursing assistants and home care aides.
AB  - This study compares differences in attitude, of oral health care of nursing
      personnel working with dependent elderly and severely disabled patients. A
      questionnaire was administered to 398 personnel covering (1) personal oral health
      care habits, (2) experiences and attitudes in assisting oral care and (3)
      willingness to assist patients/residents with their daily oral hygiene. Three
      hundred and sixty-four persons answered the questionnaire, including 70
      registered nurses, 148 nursing assistants and 146 home care aides. The study
      revealed that oral care assistance is viewed as more disagreeable than other
      nursing activities. Although registered nurses were found to have more positive
      attitudes toward oral care assistance than the other nursing groups, they were
      seldom involved in the daily practice of oral hygiene care. The results indicate
      a gap between knowledge and practice in nursing personnel's attitudes toward oral
      health care of dependent elderly and severely disabled patients.

PMID- 9610301
TI  - A reference guide to drugs and dry mouth--2nd edition.
AB  - Xerostomia (dry mouth) is an uncomfortable and potentially harmful oral symptom
      which is usually caused by a decrease in the secretion rate of saliva (salivary
      gland hypofunction, or SGH). It is more prevalent in the elderly population,
      primarily due to their increased use of drugs and their susceptibility to
      disease. Many drugs and drug classes have been linked to xerostomia; the
      xerogenic effect increases when many drugs are taken concurrently. This Reference
      Guide to Drugs and Dry Mouth is designed to allow the reader to rapidly identify
      those pharmacologic agents which have the capacity to induce xerostomia and SGH.
      Xerogenic drugs can be found in 42 drug categories and 56 sub-categories. A guide
      to the management of drug-induced SGH and xerostomia is also provided.

PMID- 9610302
TI  - The development of patient information leaflets. Care of the mouth after
      radiotherapy.
AB  - OBJECTIVES: Describe the methodology used to produce a patient leaflet on care of
      the mouth after radiotherapy. DESIGN: Prospective study to design a patient
      information leaflet. SETTING AND SUBJECTS: Patients undergoing radiotherapy for
      oral cancer. INTERVENTION: After a review of the relevant literature, a patient
      questionnaire was produced. This was then completed by patients undergoing
      radiotherapy treatment and gave an indication of the problems being encountered.
      Healthcare professionals were surveyed for their views. A leaflet was then
      produced according to published guidelines. It was taken back to another group of
      patients and a further version produced after input from a health promotion
      group. RESULTS: A leaflet was produced after wide consultation and survey.
      CONCLUSIONS: Considerable effort must to be put into the production to patient
      information leaflet. It must be discussed with patients in the target group if it
      is to be sensitive, understood and find acceptance among its users.

PMID- 9610303
TI  - A preliminary assessment of intra-oral lubricating systems for dry mouth
      patients.
AB  - OBJECTIVE: To provide extended intra-oral delivery of a saliva substitute.
      INTERVENTION: Three different types of prostheses containing saliva substitute
      were designed and assessed: a two-part device resembling a mandibular complete
      denture sealed by cobalt-samerium magnets, a one-part clear resin device for the
      edentate patients and a flexible mouth guard type of appliance containing a
      lubricant releasing bubble for the dentate patients. SETTING: A teaching hospital
      Oral Medicine and Rheumatology Clinic. SUBJECTS: 8 edentate and 3 dentate Sjogren
      Syndrome sufferers. OUTCOME MEASURES: Subjective dryness after a week of wearing
      the lubricating appliance. RESULTS: The majority of the subjects wore the
      appliances for 6-12 hours during each 24 hours. The initial dryness severity
      diminished after wearing the lubricating prosthesis. The patients preferred to
      wear the appliance at night. CONCLUSION: All criteria were fulfilled on designing
      a saliva substitute lubricating appliance and some of the subjects have worn this
      prosthesis successfully for up to 3 years. Particular benefit was obtained by
      night-time wear.

PMID- 9610304
TI  - Geroprosthodontics: The Nijmegen and Manchester Dental Schools approach.
AB  - If quality of care for elderly patients is to be achieved, thorough and realistic
      geroprosthodontic treatment planning is essential. This requires mature
      consideration, incorporating comprehensive patient assessment and selection of
      the most appropriate treatment option for each patient. The latter should be
      based on criteria which meet the demands of a healthy dentition and which enable
      a patient to achieve satisfactory oral function. The Nijmegen and Manchester
      Dental Schools have evolved simple patient-related treatment guidelines. These
      start with a problem-oriented approach which leads to a provisional treatment.
      The provisional treatment is intended to result in a healthy dentition that is
      monitored over an appropriate period. Evaluation of the provisional treatment
      leads to three options: extension of the monitoring time, preservation of the
      natural occlusion or loss of the natural occlusion. Definitive prosthodontic
      treatment plans are based on the second or third option. In the maintenance of
      good oral health after prosthodontic treatments, plaque and diet control are
      essential elements. Recall or maintenance programmes must be carried out if
      successful treatment is to be achieved and maintained.

PMID- 9610305
TI  - "The pitfalls and merits of using commonly accepted orthodontic cephalometric
      analyses".
AB  - With these thoughts in mind, a realistic, systematic approach can be designed to
      better develop and interpret cephalometric tracings. After all landmarks are
      traced and located, connect Sella to Nasion to D point. The triangle formed by
      connecting these landmarks without other planar values interfering will
      facilitate evaluation of these three landmarks to each other. With the apex of
      the triangle formed at D point, the angle formed by Sella-D point and D Axis
      should be anterior to an iscosoles triangle position. If not, the patient is
      likely to evidence a vertical growth and mandibular retrognathism, or the Sella
      Nasion pattern plane has a severely flat cant. In cases where this same apex
      (SDN) is severely anterior to an "iscosoles angle," this patient is likely to
      have either mandibular prognathism or a steep cant of the Sella-Nasion Plane (see
      Figs. 11 and 12). To determine the relative cant of Sella-Nasion, locate and
      trace the desired planar position of Frankfurt Horizontal using one of the three
      choices listed previously. If the Sella-Nasion Plane is 10 degrees or more
      greater than the cant of Frankfurt Horizontal, the Sella-Nasion plane will be
      inaccurate as a reference plane for A point, B point and D point gnathic
      relations, as well as Occlusal Plane to Sella-Nasion. Once it has been
      established which horizontal reference plan is to be used, the relative positions
      of the remaining planar values can be traced and compared. In so doing, more
      accurate interpretation of cephalometric data can be achieved without the
      puzzling conflicts with other analysis values that might otherwise occur.

PMID- 9610306
TI  - "The importance of nutrition in TMJ treatment, periodontal treatment and
      dentistry".

PMID- 9610307
TI  - Case report: air rotor stripping and lower incisor extraction to resolve mild
      crowding.

PMID- 9610309
TI  - Psychophysical subtypes of temporomandibular disorders.
AB  - This study presents an approach to the classification of temporomandibular
      disorders (TMD) based on acknowledgement of the interaction of physical,
      psychologic, and social factors using a multidimensional instrument that has been
      previously validated. The psychometric properties of this instrument were
      reevaluated in 140 women with TMD. Multidimensional clustering identified three
      subgroups of patients with TMD, including a highly distressed, psychosocially
      maladaptive group; a moderately distressed, behaviorally functional group; and a
      predominantly physical disorder group with an unremarkable psychosocial profile.
      These groups were termed maladaptive, adaptive, and uncomplicated, respectively,
      according to the constellation of predominant symptoms and psychosocial profiles
      of each cluster. The groups showed no consistent differences in pain frequency,
      use of medication, or duration of pain. This finding supports earlier work that
      suggested the prominence of three subtypes of this disorder according to both
      physical illness and psychosocial illness impact parameters.

PMID- 9610308
TI  - Effects of adjuvant on neuropeptide-like immunoreactivity in the
      temporomandibular joint and trigeminal ganglia.
AB  - To study the role of the nervous system in temporomandibular joint arthritis,
      substance P-, calcitonin gene-related peptide-, and neuropeptide Y-like
      immunoreactivity in the trigeminal ganglia and temporomandibular joint of rats
      was examined. Arthritis was induced in female Lewis rats through bilateral
      injection of a suspension of heat-killed Mycobacterium butyricum in paraffin oil
      into the temporomandibular joint. Control rats received paraffin oil via the same
      route. Tissues were collected for neuropeptide extraction 28 days after injection
      and analyzed by radioimmunoassay and reverse-phase high-performance liquid
      chromatography. Calcitonin gene-related peptide was significantly increased in
      the arthritic trigeminal ganglia. Substance P, calcitonin gene-related peptide,
      and neuropeptide Y in the arthritic temporomandibular joint were significantly
      increased as compared to controls. The results of this study show that sensory
      and sympathetic neuropeptides may possibly be associated with the development of
      arthritis in the temporomandibular joint of rats.

PMID- 9610310
TI  - A comparison of TMD patients with or without prior motor vehicle accident
      involvement: initial signs, symptoms, and diagnostic characteristics.
AB  - The role of trauma in the etiology of temporomandibular disorders (TMD) is
      controversial. The objectives of this study were to compare presenting signs,
      symptoms, and diagnoses in patients who had motor vehicle accident trauma-related
      TMD to patients who had nontrauma-related TMD. Files of 50 trauma and 50 matched
      nontrauma TMD patients were reviewed. Information concerning presenting pain,
      temporomandibular joint (TMJ) and related symptoms, examination findings, and
      diagnoses was recorded. Posttraumatic TMD patients reported higher facial (P =
      .006) and headache (P = .0001) pain ratings, neck symptom frequency (P < .01),
      ear-related symptoms (P = .02), sleep disturbance (P < .001), and occupational
      and avocational disability frequencies (P < .0001). They had greater masticatory
      muscle (P < .001), neck muscle (P < .001), and TMJ tenderness (P = .01) scores
      and myofascial pain (P = .006) and arthralgia/capsulitis (P = .008) diagnoses.
      The nontrauma group had more subjective (P = .02) and objective (P = .05) TMJ
      crepitus and higher self-reports of parafunctional jaw habits (P = .05). Trauma
      may be an important etiologic factor for some TMD patients.

PMID- 9610311
TI  - Generalized joint laxity and temporomandibular disorders.
AB  - Temporomandibular disorders (TMD) has been suggested to be of multifactorial
      etiology. One factor that has been suggested is laxity of joint ligaments. The
      purpose of this study was to evaluate the relationship between generalized joint
      hypermobility and TMD. Thirty-eight asymptomatic volunteers and 62 symptomatic
      patients were included in this study. All asymptomatic volunteers did not have
      temporomandibular joint pain, limited jaw movement, joint sounds, or previous TMD
      treatment. All subjects had bilateral magnetic resonance imaging scans in the
      sagittal closed and opened and coronal closed positions. The Beighton test was
      used to score joint laxity with a laxity score of > or = 4 to define generalized
      joint laxity. The symptomatic group had an increase in joint laxity as compared
      to asymptomatic control subjects (odds ratio 4.0 [95% confidence interval = 1.38
      to 10.95, P = .01]). There were no differences in laxity between male and female
      symptomatic subjects (P > .05). This study suggests a positive correlation
      between generalized joint laxity and TMD.

PMID- 9610312
TI  - Diagnostic accuracy of sagittal condylar movement patterns for identifying
      internal derangement of the temporomandibular joint.
AB  - The aim of this study was to compare sagittal condylar movement patterns (SCMP,
      Axiograph) and high-field (1.5 T) magnetic resonance imaging (MRI) findings of
      the temporomandibular disorders. One hundred forty-one patients with TMD signs
      and/or symptoms were selected for this study. SCMP was categorized into six
      patterns: normal, figure-eight (early/intermediate/late), limited, and other
      irregularities. The MRI findings of TMJ internal derangement were defined as one
      of five stages according to Wilkes criteria and then compared to the SCMP
      findings. Among normal SCMP, MRI revealed disc displacement in 27%. Sixty-three
      percent of figure-eight SCMP were regarded as stage I or II with reducible disc
      displacement. The sensitivity and specificity of SCMP for detecting TMJ internal
      derangement were 0.79 and 0.62, respectively. The point of deflection in figure
      eight SCMP and the degree of disc displacement were not significantly related.
      However, a significant relationship was observed between the point of deflection
      in figure-eight SCMP and any type of disc deformation (chi-square = 9.80, P =
      .002). Thus, SCMP is not yet accurate enough for diagnosing a TMJ condition,
      especially in the case of chronic and/or adaptive internal derangement.

PMID- 9610313
TI  - Comorbidity between myofascial pain of the masticatory muscles and fibromyalgia.
AB  - This study compared myofascial pain of the masticatory muscles to fibromyalgia.
      Study data show that, in both myofascial pain and fibromyalgia patients, facial
      pain intensity and its daily pattern and effect on quality of life are very
      similar. This indicates that fibromyalgia should be included in the differential
      diagnosis for myofascial pain of the masticatory muscles. However, with the
      higher prevalence of neurologic and gastrointestinal symptoms, and the stronger
      words used to describe the affective dimension of pain, it is apparent that
      fibromyalgia may be a more debilitating condition than myofascial pain of the
      masticatory muscles. Since the intensity of facial pain was strongly and
      significantly correlated to the body-pain index in fibromyalgia but not in
      myofascial pain patients, it can be concluded that facial pain may be part of the
      clinical manifestations of fibromyalgia, but it is unlikely to be related to body
      pain in myofascial pain patients. On the other hand, while body pain is episodic
      in most myofascial pain patients, it is constant and more severe in the majority
      of fibromyalgia patients. This difference in the pain patterns suggests that body
      pain in fibromyalgia and myofascial pain could have different etiologies. The
      lack of correlation between the intensity of pain and the length of time since
      onset also supports the concept that myofascial pain of the masticatory muscles
      and fibromyalgia are unlikely to be progressive disorders.

PMID- 9610314
TI  - Association between TMD treatment need, sick leaves, and use of health care
      services for adults.
AB  - The objective of this study was to analyze the relationship between need for
      treatment of temporomandibular disorders, sick leaves, and use of health care
      services in a study population of 441 adults born between 1927 and 1967. The
      findings indicated that these were strongly associated. The results were in
      agreement with earlier studies suggesting that stomatognathic disorders are one
      link between medicine and dentistry in health care. Subjects with
      temporomandibular disorders were significantly more often on sick leave, visited
      a physician more often, and had more physiotherapy and massage than subjects who
      did not need treatment for temporomandibular disorders. Intervention studies are
      needed to improve cooperation between different specialties, to eliminate
      unnecessary examinations as well as ineffective treatment modalities, and to
      decrease the cost of health care.

PMID- 9610315
TI  - Short-term effect of glucocorticoid injection into the superficial masseter
      muscle of patients with chronic myalgia: a comparison between fibromyalgia and
      localized myalgia.
AB  - The aim of this study was to investigate whether the treatment effect of
      intramuscular glucocorticoid injection differs between patients with fibromyalgia
      and those with localized myalgia of the masseter muscle concerning pain,
      tenderness to digital palpation, pressure pain threshold, pressure pain tolerance
      level, maximum voluntary occlusal force, or intramuscular temperature. Twenty
      five patients with fibromyalgia and 25 patients with localized myalgia of the
      masseter muscle were first asked to assess their pain on a visual analogue scale;
      afterward, a routine clinical examination, including tenderness to digital
      palpation, was performed. For each patient, the pressure pain threshold, pressure
      pain tolerance level, and maximum voluntary occlusal force, as well as the
      intramuscular temperature, were recorded. Finally each patient received an
      injection of glucocorticoid. The examination and glucocorticoid treatment were
      repeated after approximately 2 weeks, and a follow-up was performed after another
      5 weeks. In the fibromyalgia group, there was a reduced tenderness to digital
      palpation in response to the treatment. The localized myalgia group responded
      with a general improvement of symptoms as well as a significant reduction of pain
      intensity and tenderness to digital palpation. The results of this study indicate
      that patients with fibromyalgia and localized myalgia in many respects show a
      similar response to local glucocorticoid treatment.

PMID- 9610316
TI  - Long-term follow-up study on drop-out TMD patients with self-administered
      questionnaires.
AB  - Although patient attrition might be a serious threat to the validity of treatment
      outcome studies on temporomandibular disorders (TMD), studies on TMD patient
      attrition are scarce. Of the 1405 consecutive TMD patients examined in a recent
      10-year period, 367 (26.1%) drop-out patients or patients identified with a
      control group were sampled. A mailed questionnaire failed to reach 41 patients,
      and 203 (62.3%) were returned. The questionnaire elicited information on reasons
      for dropping out, changes in symptoms, treatment received in other clinics after
      dropping out, present treatment needs, and current signs and symptoms. Dropouts
      were divided into two groups: (1) those who failed to show up for their first
      scheduled appointment after the clinical examination; (2) those who failed to
      complete treatment. A group of patients who were judged by the examiner not to
      need treatment were included as a control group. The main reasons for dropping
      out were environmental obstacles, perceived improvement of the disease, and
      dissatisfaction with services. Only 21.7% considered themselves to be in need of
      treatment, and only 10.3% had visited other clinics after dropping out. Only 8.9%
      complained of the continued aggravation of symptoms, whereas 57.6% reported
      improvement. In addition, pain, dysfunction, and daily activity limitation tended
      to improve with time, although temporomandibular joint noise tended to persist.
      These results suggest that TMD signs and symptoms tend to decrease in patients
      after dropping out, and that the natural fluctuation of TMD signs and symptoms
      should be taken into consideration when treating TMD.

PMID- 9610317
TI  - Reaching your practice potential.

PMID- 9610318
TI  - Pediatric dentistry: a vital component in the delivery of oral health care.

PMID- 9610319
TI  - Contemporary adhesive restorative dentistry--an update on materials.

PMID- 9610320
TI  - Marginal adaptation of dental composites containing prepolymerized filler.
AB  - Marginal adaptation to cylindrical dentin preparations of five commercially
      available dental composites--Charisma, Estelite, Herculite, Pertac, and Silux
      Plus--and seven experimental dental composites containing prepolymerized filler
      was evaluated by measurement of the wall-to-wall polymerization contraction gaps.
      The experimental composites were prepared with varying amounts of spherical
      inorganic filler particles, irregularly shaped prepolymerized filler particles,
      and a base resin matrix composed of BIS-GMA and TEGDMA. Cylindrical dentin
      preparations, approximately 3.0 mm in diameter and 1.5 mm deep, were prepared in
      the exposed approximal dentin surfaces of extracted human molars. These cavity
      preparations were pretreated with an experimental dentin bonding system
      consisting of 0.5 mol/L EDTA, 35% glyceryl methacrylate, and Clearfil Photo Bond,
      then restored with each composite. Complete marginal adaptation was observed in
      two composites (Silux Plux and Estelite). Wall-to-wall contraction gaps were
      significantly related to the amount of ashed inorganic component in the
      composites (0.01 < P < 0.05) and to the spherical inorganic filler content by
      volume (P < 0.01).

PMID- 9610321
TI  - The effect of alcoholic and nonalcoholic mouthwashes on heat-treated composite
      resin.
AB  - Studies show that mouthwashes containing alcohol soften the surface of composite
      resin restorations. The present study determined weight change over time in heat
      treated composite resin soaked in alcohol and nonalcohol-containing mouthwashes.
      The results indicate that samples soaked in mouthwashes containing alcohol gained
      significantly more weight than samples soaked in nonalcoholic mouthwashes.

PMID- 9610322
TI  - The effect of air abrasion on shear bond strength to dentin with dental
      adhesives.
AB  - This study compared the effects of different dentin surface treatments on the
      shear bond strengths of three adhesive systems. The adhesive systems included a
      resin-modified glass ionomer, Fuji II LC, and two dentin bonding systems, One
      Step and Scotchbond Multi-Purpose Plus. The surface treatments compared for each
      adhesive system were as follows: 1) the controls, which were conditioned, 2) air
      abrasion at 120 psi without conditioning, 3) air abrasion at 160 psi without
      conditioning, 4) air abrasion at 120 psi with conditioning, and 5) air abrasion
      at 160 psi with conditioning. The KCP 1000 Whisperjet was used for all air
      abrasive specimens. Controls for each adhesive material (Fuji II LC, One Step,
      Scotchbond Multi-Purpose Plus) were bonded using manufacturers' recommendations.
      Results showed that air abrasion significantly lowered bond strength of the resin
      modified glass ionomer, conditioned or nonconditioned (P < 0.01). Air abrasion
      alone significantly lowered bond strengths of the dentin bonding agent systems (P
      < 0.01). However, air abrasion plus conditioning of the dentin surface resulted
      in bond strengths that were similar to the conditioned-only specimens (P < 0.01).

PMID- 9610323
TI  - Surface characteristics of tooth-colored restoratives polished utilizing
      different polishing systems.
AB  - The surface characteristics of different tooth-colored restoratives polished with
      the Enhance system, white stones, and the Super-snap system were evaluated using
      profilometry and microhardness testing. Surface characteristics of materials
      cured against a Mylar Uni-strip were used as a control. The results of this study
      show that the surface characteristics (roughness and hardness) following
      polishing with different systems are material dependent. The result may be
      attributed to the discrepancy between filler and matrix hardness of the
      restorative. Filler content, particle size, and the ability of the polishing
      system to abrade the filler may also contribute to the observed change in surface
      characteristics.

PMID- 9610324
TI  - Three-year clinical evaluation of the Clearfil Liner Bond system.
AB  - Modern dental adhesive systems have improved the bond of restorative materials to
      mineralized tooth structures. The purpose of this study was to evaluate the
      clinical performance of composite restorations placed in abrasion and erosion
      lesions using the Clearfil Liner Bond dental adhesive system. Following ADA
      clinical guidelines for dentin and enamel adhesive materials, 62 facial class 5
      smooth surface erosion or abrasion lesions with no undercuts and involving
      primarily root surfaces were restored in 25 adult male and female patients. The
      teeth were restored without preparations using Clearfil Liner Bond and Clearfil
      Photo Anterior composite resin. The clinical performance of the restorations was
      assessed by two examiners at baseline, 6 months, 1, 2, and 3 years using the
      following evaluative parameters: color match, marginal discoloration, and
      marginal integrity according to modified Ryge criteria; the presence or absence
      of recurrent decay; pre- and postoperative sensitivity; and restoration failure
      due to loss of retention or other causes. At the end of 3 years, four of the 55
      restorations remaining in the study failed due to lack of retention (92.7%
      retention rate). The evaluations of the other clinical parameters demonstrated
      excellent performance by this system.

PMID- 9610325
TI  - Trends in clinical dentistry skills observed by board examiners: a 15-year
      comparison.
AB  - This study compares and analyzes the clinical performance of recent dental
      graduates over a 15-year period. A majority of the 981 board examiners,
      cumulatively surveyed, observed an increase in diagnosis/treatment planning and
      periodontal skills, and a decrease in operative and prosthodontic skills, while
      many other skills were performed at approximately the same level.

PMID- 9610326
TI  - Effect of home-use fluoride gels on resin-modified glass-ionomer cements.
AB  - Acidic fluoride gels have been found to significantly damage conventional glass
      ionomer cements. In this study the effect to acidulated phosphate fluoride (APF)
      and neutral fluoride gels on the recently introduced resin-modified glass
      ionomers and a polyacid-modified composite resin (Variglass) was studied using
      scanning electron microscopy (SEM). Five materials were examined: Photac-Fil,
      Fuji II LC, Vitremer, Variglass, and Ketac-Fil (control). Groups of five
      specimens of each material were treated for 24 hours with one of the following:
      1) distilled water, 2) neutral fluoride gel, 3) APF gel. Surface micro-structure
      of treated specimens was examined using SEM, and microphotographs were evaluated
      using a three-point scale. APF was found to have a deleterious effect on all
      examined materials, while minimal effects resulted from the neutral fluoride gel
      compared to the control group. Although showing greater resistance to the APF gel
      than conventional glass-ionomer cements, resin-modified glass-ionomer materials
      revealed characteristic immersion and erosion behavior, substantiating their
      differentiation from a hybrid material containing a preponderance of resin.

PMID- 9610327
TI  - A study on the radiopacity of different shades of resin-modified glass-ionomer
      restorative materials.
AB  - There are several resin-modified glass-ionomer restorative materials available to
      the dental profession today. The commercially available brands are presented in a
      range of shades. There is little information on their radiopacity and whether
      this varies with differences in shade. While the general radiopacity of various
      products may have been studied, only assumptions are available regarding their
      consistency between shades. The purpose of this study was to investigate if there
      were any significant differences in the radiopacity of the shades available
      within each commercial product. The products evaluated were Fuji II LC, Vitremer,
      and Photac-Fil. The optical densities of standardized radiographs of samples of
      these materials were determined and radiopacity values of materials expressed in
      millimeter equivalents of aluminum. Of the three resin-modified glass-ionomer
      restorative materials tested, Fuji II LC was the most radiopaque and Photac-Fil
      the least. Fuji II LC and Vitremer showed radiopacity values equivalent to > 2.5
      mm and > 1.5 mm aluminum respectively; Photac-Fil demonstrated very low
      radiopacity values (equivalent to < 0.6 mm aluminum). Statistical analysis
      revealed that there was no significant difference in radiopacity among the shades
      within each of these brands.

PMID- 9610328
TI  - Effects of surface treatments on amalgam repair.
AB  - Dentists are faced with clinical situations that require the decision to replace
      or repair an amalgam restoration. The purpose of this study was to compare five
      amalgam repair techniques. Six groups of 15 amalgam beams each were fabricated by
      mechanical condensation of Tytin into an anodized aluminum split mold. Specimens
      were aged for 7 days prior to repair. Repaired specimens were stored for 7 days
      and thermocycled 500 times. Repair strength was measured by transverse strength
      testing in an Instron testing machine. Data were analyzed by a one-way ANOVA and
      a Student-Newman-Keuls test at the P < or = 0.05 level. The surface treatments
      were: Group A) intact beams, B) roughened with a #557 bur, C) air abraded with 50
      microns aluminum oxide, D) retentive undercuts with a #33 1/2 bur, E) Amalgambond
      Plus, and F) no treatment. The repair strength of the various experimental groups
      ranged from 7-18% of the intact specimens. The #557 bur-roughened group yielded
      statistically higher repair strengths than all other surface treatments, which
      were statistically equivalent to each other.

PMID- 9610330
TI  - Microleakage of dentin/amalgam alloy bonding agents: results after 1 year.
AB  - The purpose of this study was to evaluate the 1-year results of the dentin bond
      (DBS)/viscous resin liner combinations Amalgambond Plus, Tenure/Panavia,
      Syntac/Dual Cem, and All-Bond 2/Liner F in reducing microleakage in class 5
      cavity preparations restored with an admixed or a spherical amalgam alloy and to
      compare these results to the previously reported short-term (4-day) data from
      this same study. Class 5 cavity preparations with occlusal margins in enamel and
      gingival margins in cementum were prepared on extracted human molar teeth.
      Prepared teeth were distributed randomly into 12 treatment groups (n = 10)
      consisting of the various DBS/ liners, Copalite, and no liner for each alloy.
      Samples were stored in saline for 12 months, thermocycled, and stained with dye.
      Restorations were sectioned and microleakage scored. The DBS/liner combinations,
      with the exception of Syntac/Dual Cem, had significantly less microleakage with
      both alloys than Copalite or no liner. Comparing short-term to long-term results
      within the DBS/liners, only Tenure/ Panavia with Tytin had a significant increase
      in microleakage scores. These data indicate DBS/ liner combinations can provide
      significant protection against microleakage under high-copper amalgam alloys for
      up to 1 year.

PMID- 9610329
TI  - Monkey pulpal responses to conventional and adhesive luting cements.
AB  - Monkey pulpal responses to metal inlays luted with a combination of an adhesive
      resin and luting composite and conventional dental cements were
      histopathologically evaluated. Initial pulpal responses caused by re-exposure of
      the cut dentin surfaces and luting procedure under hydraulic pressure subsided at
      90 days after final cementation. There was no significant difference among pulpal
      reactions to conventional dental cements and a combination of an adhesive resin
      and luting composite. The adhesive resin coating of freshly cut dentinal
      walls/floors immediately after cavity preparation seems to provide protection for
      the dentin and pulp in indirect restorations requiring temporary sealing.

PMID- 9610332
TI  - Implants in mandibular resection.
AB  - This clinical report presents a method of satisfactorily restoring a patient with
      a Class V mandibular defect. Conventional restoration of this patient would have
      consisted of a soft tissue-supported prosthesis with its inherent instability and
      associated problems. The use of implants has provided stability and function
      unobtainable with conventional prosthesis for this patient.

PMID- 9610331
TI  - The effect of three finishing systems on four esthetic restorative materials.
AB  - Previous studies have investigated the finishing and smoothness of composite and
      traditional glass-ionomer restorations, but few have included resin-modified
      glass-ionomer cements or more recent finishing systems. The results of using
      three different finishing systems (Sof-Lex, Enhance, finishing burs) on two
      composites (Silux, Prisma TPH), a traditional glass ionomer (Ketac-Fil), and a
      resin-modified glass ionomer (Fuji II LC) were studied. Sixty samples were
      condensed into sectioned acrylic tubes, covered with a Mylar matrix plus a glass
      slide at each surface, then cured as per the manufacturers' instructions. Samples
      were randomized to three groups of five for each material and testing with a
      Surfanalyzer 4000 of unfinished samples (cured with Mylar matrix) was done to
      obtain baseline average surface roughness (Ra). Samples were then finished as per
      the manufacturers' instructions using polishing disks, abrasive impregnated
      disks, and finishing burs before further surface testing. Samples finished with
      burs and with abrasive impregnated disks were further polished using polishing
      paste (Prisma Gloss) and again tested. Data were analyzed with ANOVA testing and
      Tukey's HSD pairwise comparison. Initial testing after randomization to groups
      showed no significant difference in surface roughness (P = 0.24). Two-factor
      analysis revealed no significant difference between materials (P = 0.34), a
      significant difference in method of finish (P < or = 0.00), with no significant
      interaction between type of material and method of finish (P = 0.11). Aluminum
      oxide disk and impregnated disk systems provided the best finish for microfilled
      composite and both glass-ionomer materials (P < or = 0.00). No significant
      difference in method of finish existed with the hybrid composite (P = 0.07).
      Overall, esthetic restorative material finishing is best accomplished using
      abrasive impregnated disks or aluminum oxide disks. Finishing burs gave a
      significantly rougher surface than the former methods.

PMID- 9610333
TI  - Waiving copayments: a legal and ethical dilemma.

PMID- 9610334
TI  - The use of botulinum toxin for the treatment of temporomandibular disorder.

PMID- 9610335
TI  - Dental and dental hygiene students' attitudes in a joint local anesthesia course.
AB  - In 1995, the local anesthesia course was combined for dental and dental hygiene
      students. It was also the first time that dental hygiene students were instructed
      clinically in local anesthetic techniques. Faculty felt it important to evaluate
      student attitudes regarding these curriculum changes. This study assessed
      students' perceptions of the adequacy of background preparation courses, concerns
      about administering local anesthetics and attitudes about its administration by
      dental hygienists. A pre/post survey was completed by dental and dental hygiene
      students. T-tests were used to determine if differences in attitudes existed
      between groups and if changes in attitudes occurred within groups after taking
      the course. Results indicated that both groups believed they had adequate
      background preparation. Apprehensions about administering local anesthetics were
      similar, but the dental hygiene students felt significantly less anxiety (p <
      0.01). Results also differed significantly on the issue of hygienists
      administering local anesthetics, with hygiene students in support of it and
      dental students opposed (p < 0.01). Results confirmed that no changes were needed
      in the existing prerequisite courses for both groups. A need to address student
      anxiety about local anesthetic administration has been identified. In addition,
      it may be beneficial to expand dental students' appreciation of dental hygiene
      education to foster mutually successful working relationships in the future.

PMID- 9610336
TI  - The effects of cigarette smoking on periodontal disease.

PMID- 9610338
TI  - Recognition and management of occlusal disease from a hygienist's perspective.
AB  - Dental disease can be described as a permanent alteration of loss or function of
      those parts generally cared for by dentists. Specifically, these include the
      teeth, periodontal tissues and associated dental structures. Historically the
      breakdown and subsequent loss of tooth structure was caused by dental caries. It
      has also been observed that tooth loss can result from overuse-abuse referred to
      as bruxism or bruxamania.

PMID- 9610337
TI  - Women's oral health issues: an exploration of the literature.
AB  - As interest in women's health issues grows, there is increasing concern that
      today's practice of medicine may not meet the health needs of women. A primary
      reason is the gender bias that has been inherent in medical education, research
      and clinical practice. The prevailing medical viewpoint has often been that the
      male body is considered to be the norm and that the female body exactly the same
      except for the reproductive function. This attitude has led to a lack of interest
      in researching gender differences and a consequent lack of knowledge of women's
      health issues. Fortunately, there is a movement for change. The Women's Health
      Interschool Curriculum Committee was formed in January 1992 to develop curricula
      concerning women's health and examine bias that may exist in existing curricula.
      The Canadian Women's Health Network has been growing across the country and there
      have been calls to create a new specialty in women's health. According to Angell,
      this proposal for a new specialty was provocatively debated in the Journal of
      Women's Health, which started publication in 1992. There is also a growing
      concern on how to conduct better research to address women's health needs. As
      more attention is paid to women's health issues, what will happen in the area of
      oral health? In health care, it would seem that the mouth has become completely
      separated from the rest of the body. Health conferences rarely have any oral
      health content at all. To correct this problem, there must be an increase in
      general awareness of the importance of oral health as it relates to the overall
      health of both women and men. Good oral health is more than just decay-free
      teeth. Oral health encompasses the teeth, the supporting periodontal structures,
      soft tissues of the mouth and oral pharynx area, temporomandibular joints and
      muscles of mastication. The mouth is a gateway to the body and will also reflect
      many systemic health problems, such as diabetes, leukemia and lupus. The second
      step would be the recognition that women may have different oral health needs and
      issues than men. The common view may be that teeth are gender free, but how can
      this be when teeth exist in a body, and that body is male or female? For many
      years, the primary acknowledged difference between men and women's oral health
      was pregnancy gingivitis. Like medicine, dentistry must re-examine the viewpoint
      that women's oral health differs from men's only as it is influenced by
      reproductive processes. There are many areas where women's oral health may differ
      from that of men. This paper will explore the literature for potential women's
      oral health issues in the areas of oral hygiene behaviours, esthetics, eating
      disorders, temporomandibular disorders, and hormonal influences on periodontal
      health.

PMID- 9610339
TI  - Local effects of nitric oxide supplementation and suppression in the development
      of intimal hyperplasia in experimental vein grafts.
AB  - OBJECTIVES: The universal response of vein grafts after insertion into the
      arterial circulation is the development of intimal hyperplasia; smooth muscle
      cell proliferation and connective tissue deposition, which may be modulated in
      part by dysfunctional endothelial nitric oxide (NO) metabolism. This study
      examines the effects of single dose, local application by pluronic gel of a NO
      donor, S-nitroso-N-acetylpenicillamine (SNAP) and an NO synthase inhibitor nitro
      L-arginine methyl ester (L-NAME) on the formation of intimal hyperplasia.
      MATERIALS: Forty New Zealand white rabbits underwent jugular vein interposition
      grafting of the common carotid artery. DESIGN: Ten animals were controls, 10
      animals had the outer surface of the vein graft coated with 30% pluronic gel (2.5
      ml), and 10 each were immersed for 15 min prior to insertion in Ringer lactate
      containing 10(-3) M of SNAP or L-NAME and then had their vein grafts coated with
      2.5 ml of gel containing either SNAP (10(-3) M) or L-NAME (10(-3) M), which
      allows for sustained delivery for up to 6 h. On the 28th post operative day, the
      animals were sacrificed and vein grafts were harvested for morphology by electron
      microscopy (SEM and TEM) and dimensional analysis by videomorphometry. RESULTS:
      All vein grafts developed intimal hyperplasia. On SEM the vein grafts had a
      confluent layer of endothelial cells with multiple layers of smooth muscle cells
      representing intimal hyperplasia in TEM. There were no demonstrable morphological
      differences between the four groups. Local treatment with SNAP produced a
      significant 36% decrease in mean intimal thickness (72 +/- 4 microns vs. 45 +/- 4
      microns; mean +/- S.E.M.; p < 0.01) without a change in medial thickness compared
      to gel-only treated groups (58 +/- 6 microns vs. 61 +/- 7 microns; p = ns).
      Inhibition of NO synthase by L-NAME had no effect on the development of intimal
      hyperplasia (72 +/- 4 microns vs. 79 +/- 10 microns; p = ns); medial thickness
      was also unchanged. CONCLUSION: These data confirm the protective effect of NO in
      vascular injury and suggest that NO synthase activity is either absent or reduced
      to such a level that further inhibition in this short time course is not relevant
      to the pathophysiology of vein graft intimal hyperplasia.

PMID- 9610340
TI  - Biomechanics of abdominal aortic aneurysm in the presence of endoluminal
      thrombus: experimental characterisation and structural static computational
      analysis.
AB  - OBJECTIVES: To evaluate the role played by biomechanical and geometrical
      parameters of endoluminal thrombus and of aortic wall on abdominal aortic
      aneurysm (AAA) behaviour. MATERIALS AND METHODS: Tensile tests on 21 AAA thrombus
      specimens from six patients undergoing AAA repair and numerical evaluation of
      aneurysmal aortic wall stress and strain distribution. Parameters of the analysis
      were lumen eccentricity, thrombus Young's Modulus and the aortic wall
      constitutive equation. RESULTS: There was a linear stress/strain for all the
      thrombus specimens. The numerical analyses show the mechanical behaviour of AAA
      as a function of lumen eccentricity and biomechanical parameters. CONCLUSIONS:
      Well organised thrombus reduces the effect of the pressure load on the aneurysmal
      aortic wall.

PMID- 9610341
TI  - Oral iloprost in the treatment of thromboangiitis obliterans (Buerger's disease):
      a double-blind, randomised, placebo-controlled trial. The European TAO Study
      Group.
AB  - OBJECTIVES: To assess efficacy and tolerability of two dosages of the oral
      prostacyclin analogue iloprost versus placebo in thromboangiitis obliterans
      (TAO). DESIGN: Placebo-controlled, double-blind, study; TAO patients randomised
      to iloprost 100, 200 micrograms, or placebo bid for 8 weeks, with 6 months'
      follow-up. METHODS: Three-hundred and nineteen TAO patients with rest pain,
      trophic lesions (or both) from 23 clinics in six European countries. Primary
      endpoint: total healing of most important lesion. Secondary endpoint: relief of
      rest pain without need of analgesics. Combined endpoint: alive without major
      amputation, no lesions, no rest pain, no use of analgesics. RESULTS: Total
      healing of lesions was not significantly different between treatment groups at
      any time point. For relief of rest pain without need of analgesics, low dose (LD)
      iloprost was significantly more effective than placebo at end of follow-up
      (placebo 49%; LD iloprost 63%; p = 0.020). This also applied to the combined
      endpoint (placebo 35%; LD iloprost 50%; p = 0.016). High dose iloprost (HD)
      failed to show significant treatment effects over placebo. CONCLUSIONS: Iloprost
      LD was significantly more effective than placebo for relief of rest pain without
      need of analgesics and for a combined endpoint at 6 months of follow-up, whilst
      both iloprost doses showed no significant effects vs. placebo on total healing of
      lesions.

PMID- 9610342
TI  - A dynamic view on the diameter of abdominal aortic aneurysms.
AB  - OBJECTIVES: To study 40-55 mm aneurysms and calculate their size in relation to
      the individual predicted normal aortic diameter to see if this might add anything
      in the evaluation of treatment. MATERIAL AND METHODS: The anteroposterior
      diameter of 40-55 mm AAAs was measured with an echo-tracking ultrasonic technique
      in 147 consecutive patients. The weight and height were registered and body
      surface area calculated. The predicted normal aortic diameters were defined
      according to nomograms and the diameter increase from the predicted normal aortic
      size in the individual aneurysms calculated. RESULTS: The median AAA diameter was
      48 mm (range 40-55), the BSA 1.85 m2 (1.42-2.37), and the predicted AO size 19.4
      mm (14.3-21.6). The calculated increase of size in the individual aneurysms was
      2.51 (1.9-3.53), that is the spread of data doubled as compared to conventional
      diameter measurements. When females and males were studied separately the AAA
      diameter was 46.5 mm (40-55) and 48 mm (40-55), respectively (NS). Since the BSA
      was significantly lower in women than in men, 1.63 (1.42-1.95) and 1.89 (1.47
      2.37), respectively (p < 0.0001), also the predicted normal aortic size was
      lower, 16.4 (14.3-17.8) vs. 19.7 (18.0-21.6) (p < 0.0001). Thus, the AAA diameter
      increase from the predicted size was larger in women than in men; 2.93 (2.25
      3.53) vs. 2.46 (1.90-2.94), respectively (p < 0.0001). CONCLUSION: To define an
      aneurysm as a localised dilatation of an artery exceeding 50% of the expected
      normal diameter is now possible. This may facilitate how to treat especially
      smaller aneurysms and give new information concerning patterns of growth and risk
      of rupture.

PMID- 9610343
TI  - Chronic inflammation and elastin degradation in abdominal aortic aneurysm
      disease: an immunohistochemical and electron microscopic study.
AB  - OBJECTIVES: To investigate (i) elastin degradation and the possible association
      between proteolysis and inflammation in abdominal aortic aneurysm disease (AAA),
      and (ii) the presence of cytomegalovirus (CMV) infection in the walls of AAA.
      MATERIALS: Specimens from 12 infrarenal AAAs, eight aortas with occlusive disease
      (AOD) and two normal aortas were studied by conventional light microscopy,
      immunohistochemistry using a monoclonal anti-elastin antibody BA-4 and anti-CMV
      antibody and transmission electron microscopy (TEM). MAIN RESULTS: In AAA the
      decrease in elastin immunoreactivity and the presence of elastin degradation was
      associated with increased mononuclear inflammatory cell infiltrates (p = 0.004
      and p = 0.00002, respectively). The CMV immunostainings of the normal aortic wall
      and all the AAA and AOD samples were negative, nor could any CMV particles be
      demonstrated by TEM. CONCLUSIONS: The chronic inflammation and degradation of
      elastin in AAA suggests a possible immune-mediated mechanism. The inflammation
      may be induced by the chemotactic properties of elastin-derived peptides.

PMID- 9610345
TI  - Below-knee popliteal and distal bypass with PTFE and vein cuff.
AB  - OBJECTIVES: To determine the value of PTFE grafts with a distal vein cuff as a
      conduit for below-knee (BK) popliteal and distal bypass in the absence of
      autologous vein. DESIGN: Retrospective study. MATERIALS AND METHODS: Forty below
      BK popliteal and distal bypass procedures in 39 patients with PTFE and distal
      vein cuff (Miller cuff n = 31, Wolfe cuff and adjuvant arteriovenous fistula n =
      9). Nineteen primary and 21 secondary reconstruction procedures. RESULTS: The
      primary patency rate was 62.5% at 1 year falling to 50% at 2 years. The secondary
      patency rates were very similar owing to poor outcome of thrombectomy. Ten cases
      (25%) resulted in major amputation postoperatively. There was a tendency towards
      better outcome for primary procedures compared to secondary/redo procedures.
      CONCLUSIONS: BK popliteal and distal bypass with PTFE and distal vein cuff is a
      worthwhile procedure in the absence of autologous vein. The value of thrombectomy
      following thrombosis of a secondary bypass procedure with PTFE and distal vein
      cuff is questionable.

PMID- 9610344
TI  - The use of the gastroepiploic artery for peripheral revascularisation. A study in
      pigs.
AB  - OBJECTIVES: To use the autologous gastroepiploic artery (GEA) as arterial bypass
      graft for peripheral revascularisation. We compared the development of intimal
      hyperplasia and nitric oxide (NO) capacity in GEA and internal jugular vein (IJV)
      implanted as peripheral grafts. MATERIALS AND METHODS: In pigs the GEA was
      implanted into the right peripheral circulation as a femoropopliteal bypass
      graft. In the left peripheral circulation the IJV was implanted as a
      femoropopliteal graft. After 21 days all grafts were harvested. Vascular rings of
      each graft before and after operation were studied for NO capacity. The distal
      half of each graft was prepared for histomorphometric studies. RESULTS:
      Administration of bradykinin to IJV and GEA induced relaxation. After
      implantation bradykinin resulted in contraction in IJV grafts, whereas in GEA
      grafts relaxation was reduced. In IJV grafts extensive intimal hyperplasia was
      formed, whereas in GEA grafts only small areas of intimal hyperplasia were
      formed. CONCLUSIONS: The functional studies lost NO capacity in IJV grafts,
      whereas NO capacity in GEA grafts remained intact. Intimal hyperplasia in IJV
      grafts was extensive, whereas GEA grafts demonstrated preservation of pre
      existent intimal architecture. These results may encourage the application of the
      human GEA as bypass graft for reconstruction of arteries in the lower limb or
      foot.

PMID- 9610346
TI  - Effects of alpha-trinositol on peripheral circulation in diabetic patients with
      critical limb ischaemia. A pilot study using laser Doppler fluxmetry,
      transcutaneous oxygen tension measurements and dynamic capillaroscopy.
AB  - OBJECTIVES: To evaluate whether alpha-trinositol may have an effect on the
      microcirculation in patients with diabetes mellitus and critical ischaemia.
      MATERIAL AND METHODS: Ten patients with previously known diabetes mellitus and
      with critical limb ischaemia were given alpha-trinositol during a 24 h infusion,
      resulting in a total dose of 2400 mg. Microcirculation was evaluated by means of
      laser doppler fluxmetry (LDF), transcutaneous oxygen tension (tcPO2) and dynamic
      capillaroscopy (CBV). RESULTS: Plasma concentration of alpha-trinositol reached a
      steady state level after 1 h following the start of the administration. There
      were no detectable changes in blood pressure or heart rate. Laser Doppler flux
      increased from 41% to 57.5% and tcPO2 changed from 116 to 91 s in "half time
      recovery" after occlusion. Capillary blood flow showed an increase in resting
      velocity from 0.1 to 0.5 mm/s at 24 h. CONCLUSIONS: The infusion of alpha
      trinositol did not cause any changes in the haemodynamics in general, but
      resulted in changes in LDF(rest value), tcO2(half-time recovery) and CBV(rest
      flow) during or following the infusion suggesting improved microcirculation.

PMID- 9610347
TI  - The increasing workload required to maintain infrainguinal bypass graft patency.
AB  - BACKGROUND: To assess the impact upon the provision of a vascular service of the
      workload associated with maintaining infrainguinal bypass graft patency. DESIGN:
      A computerised prospective audit. MATERIALS AND METHODS: Between January 1990 and
      December 1995, all patients with infrainguinal bypass grafts were entered into a
      prospective computerised audit to monitor interventions for the maintenance of
      graft patency. Excluded from the study were interventions during the first 30
      postoperative days and procedures not directly related to the graft. A graft
      surveillance programme was in operation throughout. RESULTS: During the study
      period a total of 131 patients with 144 grafts were admitted on 330 occasions and
      required 401 separate interventional procedures. There were 227 procedures in 72
      femorodistal grafts, 116 in 38 below-knee femoropopliteal grafts and 58
      interventions in the group of 34 above-knee femoropopliteal grafts. Radiological
      interventions accounted for almost 70% of this workload. CONCLUSION: The workload
      associated with the maintenance of infrainguinal bypass grafts increased
      considerably during the study period, and seems likely to increase further. Such
      interventions should therefore be considered when planning for vascular service
      provision.

PMID- 9610349
TI  - Role of medial smooth muscle cell function in antithrombogenicity of vein grafts.
AB  - OBJECTIVES: To determine the significance of prostaglandin I2 (PGI2) production
      by medial smooth muscle cells (SMCs), we assessed PGI2 production from denuded
      vein grafts and their antithrombogenicity. MATERIALS AND METHODS: A total of 30
      dogs were divided into two groups: in group I, 14 dogs (27 veins, 188 segments)
      were used to assay PGI2 production, which was measured as 6-keto-PGF1 alpha. In
      group II, 16 dogs were used for an implantation study and the thrombus-free
      surface (TFS) score was calculated 24 h after implantation. Both groups contained
      the following subgroups: subgroup A, freshly harvested veins; subgroup B,
      endothelial denuded veins; subgroup C, veins frozen and cryopreserved; subgroup
      D, veins treated with protease. RESULTS: Values of 6-keto-PGF1 alpha (pg/mg/min)
      for basal and stimulated states in subgroup I-A through I-D were 58.0 +/- 8.9 and
      530.6 +/- 74.7, 26.3 +/- 4.7 and 82.3 +/- 11.4, 17.9 +/- 1.3 and 39.4 +/- 3.3,
      and 13.3 +/- 1.8 and 32.2 +/- 6.2, respectively. The PGI2 production in subgroup
      I-A were significantly higher than those in the other three subgroups (p < 0.01
      for basal and stimulated), while the production in subgroup I-B was also
      significantly higher than those in the remaining two (p < 0.05 for basal and
      stimulated). The TFS scores in subgroup II-A through II-D were 98 +/- 2%, 90 +/-
      2%, 38 +/- 5%, and 15 +/- 7%, respectively, showing significantly superior
      antithrombogenicity in subgroup II-B, as well as in II-A, when compared with the
      remaining two (p = 0.014). CONCLUSION: The amount of PGI2 generated by the medial
      SMCs may be sufficient for maintaining the antithrombogenicity of the endothelial
      denuded AVGs.

PMID- 9610348
TI  - Endothelial activation in patients with chronic venous disease.
AB  - OBJECTIVES: Leukocyte trapping due to leukocyte-endothelial activation has been
      implicated as the cause of lipodermatosclerosis and ulceration in patients with
      chronic venous disease. We investigated endothelial activity in normal controls
      and patients subjected to short-term venous hypertension. METHODS: Twenty-five
      normal volunteers and 30 patients with chronic venous disease divided into two
      groups: varicose veins with skin changes (LDS, n = 15); and varicose veins
      without skin changes (VVs, n = 15) were studied. Blood samples were taken from a
      foot vein before and after experimental venous hypertension. Plasma levels of
      ELAM-1 (endothelial leukocyte adhesion molecule-1), ICAM-1 (intercellular
      adhesion molecule-1), VCAM-1 (vascular cell adhesion molecule-1), and von
      Willebrand factor (vWf) was measured by an ELISA. RESULTS: There was a
      significant rise in the plasma concentration of ELAM-1, ICAM-1 and VCAM-1 in
      patients and normal controls in response to venous hypertension. Basal levels of
      plasma VCAM-1 and vWf were higher in patients with LDS compared to patients with
      VVs. The magnitude of rise of VCAM-1 was greater in patients with LDS compared to
      patients with VVs (p = 0.01, Mann-Whitney U-test). There was no difference in the
      basal levels or in the magnitude of change in plasma ICAM-1 and ELAM-1 between
      the two patient groups. CONCLUSION: Venous hypertension results in endothelial
      activation which may aid endothelial-leukocyte adhesion. Patients with LDS
      exhibit increased VCAM-1, which is a counterligand for receptors expressed by
      monocytes and lymphocytes signifying that these cells may be more important in
      the development of skin changes.

PMID- 9610350
TI  - The ability of qualitative assessment of the common femoral Doppler waveform to
      screen for significant aortoiliac disease.
AB  - OBJECTIVE: To study the ability of a qualitative assessment of the common femoral
      Doppler waveform to screen for significant aortoiliac disease. DESIGN:
      Prospective, semi-blind study. SETTING: Vascular laboratory, University Hospital.
      METHODS: A total of 118 aortoiliac segments were studied in 73 patients. Each
      aortoiliac segment was graded as normal or abnormal from visual interpretation of
      the common femoral Doppler waveform obtained by colour duplex ultrasound. Full
      ultrasound assessment of the aortoiliac vessels acted as the "gold standard".
      Abnormal aortoiliac segments were defined by the presence of at least one > or =
      50% diameter reducing lesion, whereas vessels considered "normal" included those
      with disease between 0-49% diameter reduction. An increase in peak systolic
      velocity of two-fold or greater was used to define a > or = 50% diameter reducing
      stenosis. Agreement between common femoral waveform analysis and the duplex scans
      was measured by the Kappa statistic. RESULTS: The Kappa value for the agreement
      between common femoral waveform analysis and duplex scans was 0.74 (95% CI; 0.62
      0.86). This represents substantial agreement. Doppler waveform analysis had a
      sensitivity of 95%, specificity of 80% and accuracy of 87% for the prediction of
      a significant aortoiliac stenosis seen by ultrasound. CONCLUSION: Visual
      interpretation of the common femoral Doppler waveform is a sensitive and accurate
      technique for the prediction of significant aortoiliac stenosis. It is of
      particular value when full ultrasound aortoiliac assessments are not feasible due
      to time constraints, obesity or the presence of bowel gas.

PMID- 9610351
TI  - Idiopathic aneurysm of the inferior vena cava as a cause of massive penile
      bleeding.

PMID- 9610352
TI  - Reconstruction of the SMA after excision of an anomalous splenic artery aneurysm.

PMID- 9610353
TI  - Are rotors at the heart of all biological motors?
AB  - Biological motors are generally divided into two classes: 1) rotary motors. These
      include ATP synthase (F0-F1) and the bacterial flagellar motor which are driven
      by proton and Na+ gradients., 2) linear motors. Myosin, kinesin and dynein are
      considered to be such motors, F-actin and microtubules serving as passive
      "tracks". However, data is presented which suggests that the actin filaments
      rotate in shortening muscle. Microtubules also have been reported to rotate upon
      interacting with kinesin and dynein. Axial protein rotation thus appears to be a
      common fundamental characteristic of actin- and of microtubule-based motility
      systems, in addition to F0-F1 and the bacterial motor. An analysis is carried out
      of the way ATP hydrolysis and randomly moving protons can induce rotation. It is
      concluded that all four engines are driven by water jets, thus operating like
      water turbines.

PMID- 9610354
TI  - Identification of testis-specific (Limk2t) and brain-specific (Limk2c) isoforms
      of mouse LIM-kinase 2 gene transcripts.
AB  - LIM-kinase 1 (LIMK1) and LIM-kinase 2 (LIMK2) are members of a novel
      serine/threonine kinase subfamily with structural features composed of N-terminal
      two LIM domains, an internal PDZ-like domain, and a C-terminal protein kinase
      domain. We recently identified and characterized the mouse Limk2 gene and two
      Limk2 transcripts (Limk2a and Limk2b) coding for proteins with distinct N
      terminal LIM structures. Here we describe two additional transcripts of the mouse
      Limk2 gene. One is a 1.7-kb transcript, termed Limk2t, which is specifically
      expressed in the testis and codes for an N-terminally truncated form of LIMK2
      consisting of only a part of a PDZ-like domain and a protein kinase domain. The
      other is a transcript, termed Limk2c, which is specifically expressed in the
      brain and codes for a protein with a 6-amino-acid insert within the protein
      kinase domain. Exons specific to the 5'-terminal extra sequence of Limk2t and the
      insert sequence of Limk2c locate between exons 5-6 and exons 8-9 in the mouse
      Limk2 gene, respectively. Testis- and brain-specific expression of Limk2t and
      Limk2c suggests specific roles in these tissues.

PMID- 9610355
TI  - Multiple isoforms of the regulatory subunit for phosphatidylinositol 3-kinase
      (PI3-kinase) are expressed in neurons in the rat brain.
AB  - Phosphatidylinositol 3-kinase (PI3-kinase) is a heterodimeric enzyme composed of
      a catalytic subunit of 110 kDa and an adaptor regulatory subunit. We investigated
      the presence and localization of five isoforms of the regulatory subunits, p55
      alpha, p55 gamma, p85 alpha, p85 beta, and p50 alpha, in the rat brain. In situ
      hybridization histochemistry using isoform-specific cRNA probes revealed that all
      five isoforms were expressed in the neurons of the brain. Interestingly, most
      neuronal cells including Purkinje cells in the cerebellum and pyramidal cells in
      the cerebrum expressed all five isoforms. Immunohistochemical staining also
      showed the localization of p55 alpha, p55 gamma, p85 alpha, and p50 alpha in the
      neuronal cells in the brain. Expression of multiple isoforms in neurons suggests
      that they may play important roles in signal transduction in the brain.

PMID- 9610356
TI  - Identification of a novel type II activin receptor, type IIA-N, induced during
      the neural differentiation of murine P19 embryonal carcinoma cells.
AB  - We have identified a novel type II activin receptor, called type IIA-N, the
      expression of which was induced during the neural differentiation of murine P19
      embryonal carcinoma cells (P19 cells). P19 cells differentiate into several cell
      types dependent on the culture conditions. The induction of type IIA-N mRNA
      occurred predominantly in conjunction with neural differentiation. Sequence
      analysis of a cDNA clone for type IIA-N indicated that type IIA-N had a 24 bp
      insertion in the juxtamembrane region of the type IIA activin receptor suggesting
      that it is an alternative splicing product of the type IIA gene. Type IIA-N was
      also identified in human and Xenopus, and the amino acid sequences of three
      species were completely conserved. The expression of type IIA-N mRNA was
      specifically detected in neuroblastoma cells among several activin responsive
      cell lines. In vivo expression of type IIA-N mRNA was detected only in the neural
      tissues such as brain and spinal cord in adult mouse, by RT-PCR. Furthermore, its
      expression in developing Xenopus embryos was restricted to the neurula and later
      stages. These results suggest that the expression of type IIA-N is specific to
      neural cells and mediates neural differentiation-specific activin signaling.

PMID- 9610357
TI  - Development of resistance to insulin-like growth factor binding protein-3 in
      transfected T47D breast cancer cells.
AB  - Insulin-like growth factor binding protein-3 (IGFBP-3) has antiproliferative
      effects in many cell types but paradoxical growth stimulation has also been
      reported. In early passages following transfection of T47D breast cancer cells
      with IGFBP-3 cDNA, the proliferation rate and serum-stimulated DNA synthesis were
      significantly reduced compared to control cells. Cell cycle analysis indicated
      that growth-inhibited IGFBP-3-producing cells accumulated in G1 phase. After
      several passages, the transfected cells became resistant to the inhibitory
      effects of IGFBP-3 and showed transiently enhanced proliferation rates despite an
      increased IGFBP-3 concentration in the medium. IGFBP-3 proteolysis did not
      account for its decreased antiproliferative activity in resistant cells. We
      hypothesize that development of resistance to the antiproliferative action of
      IGFBP-3 might be an important step in the malignant progression of breast cancer
      cells.

PMID- 9610358
TI  - Expression of NHE1 and NHE4 in rat pancreatic zymogen granule membranes.
AB  - We previously characterized a Na+/H+ exchange activity in rat pancreatic zymogen
      granules [Anderie, I., and Thevenod, F. (1996) J. Membrane Biol, 152, 195-205].
      Here we have identified the Na+/H+ exchanger (NHE) isoforms present in zymogen
      granules by functional studies with NHE inhibitors. The NHE1 specific blocker HOE
      694 [3-(methylsulfonyl-4-piperidino-benzoyl)-guanidine methanesulfonate]
      inhibited zymogen granule Na+/H+ exchange in a concentration dependent manner,
      maximally to 53 +/- 5% of controls at 100nM. The remaining Na+/H+ exchange
      activity was inhibitable by EIPA [5-(N-ethyl-N-isopropyl)amiloride] (EC50
      approximately 25 microM) or benzamil (EC50 approximately 100 microM). Amiloride
      inhibited weakly suggesting that "amiloride-resistant" and "amiloride-sensitive"
      NHE are expressed in zymogen granules. cDNA sequences encoding NHE1- and NHE4
      specific transmembrane domains were detected by RT-PCR in rat pancreatic tissue
      and in the rat pancreatic acinar cell line AR4-2J. The presence of NHE1 and NHE4
      in zymogen granule membranes was confirmed by immunoblots of zymogen granule
      membranes and by pre-embedding immunogold labeling of purified rat pancreatic
      zymogen granules with polyclonal NHE1 and NHE4 antibodies. Therefore, we propose
      that NHE1 and NHE4 are expressed in zymogen granule membranes of rat exocrine
      pancreas.

PMID- 9610359
TI  - Osteoclast differentiation factor mediates an essential signal for bone
      resorption induced by 1 alpha,25-dihydroxyvitamin D3, prostaglandin E2, or
      parathyroid hormone in the microenvironment of bone.
AB  - Osteoclast differentiation factor (ODF), a ligand for osteoprotegerin
      (OPG)/osteoclastogenesis-inhibitory factor (OCIF), induces osteoclast-like cell
      formation in vitro. To elucidate the role of ODF in the microenvironment of bone,
      we examined effects of ODF, OPG/OCIF, and anti-ODF polyclonal antibody on bone
      resorption using a fetal mouse long bone culture system. A genetically engineered
      soluble-form ODF (sODF) elicited bone resorption in a concentration-dependent
      manner and OPG/OCIF blocked the bone resorption. Anti-ODF polyclonal antibody,
      which neutralizes ODF activity, negated bone resorption induced by 1 alpha,25
      dihydroxyvitamin D3, parathyroid hormone, or prostaglandin E2. OPG/OCIF also
      abolished bone-resorbing activity elicited by these bone-resorbing agents.
      Interleukin 1 alpha-stimulated bone resorption was also significantly suppressed
      by anti-ODF polyclonal antibody and OPG/OCIF. Thus, we conclude that ODF plays a
      critical role in bone resorption in the microenvironment of bone.

PMID- 9610360
TI  - Isolation and crystallization of functionally competent Escherichia coli peptide
      deformylase forms containing either iron or nickel in the active site.
AB  - Three metallo forms of peptide deformylase (PDF, EC 3.5.1.31) of Escherichia coli
      were prepared and crystallized (space group C2, diffraction limit 1.9 A) for
      initiating the X-ray structure determination of the metal center in correlation
      with the catalytic functionality of this enzyme. The native Fe2+ containing
      enzyme species was directly isolated from overproducing bacteria by using
      catalase as a buffer additive, which stabilizes the catalytic activity against
      oxidative destruction. The Ni2+ containing form, which is oxygen-insensitive, was
      obtained by metal exchange with free Ni2+ and found to be catalytically equally
      effective (kcat/KM = 10(5) M-1 s-1 for N-formyl-Met-Ala). The Zn2+ form, prepared
      from the apoenzyme or by displacement of bound Ni2+ by free Zn2+, proved
      virtually inactive.

PMID- 9610361
TI  - The region of dopamine transporter encompassing the 3rd transmembrane domain is
      crucial for function.
AB  - Bovine dopamine transporter (bDAT) shows relatively low dopamine (DA) uptake
      efficacy and scant MPP+ transport and cocaine binding, while all of these
      activities are avid in human dopamine transporter (hDAT). In this study, we
      constructed a series of chimeras between human and bovine DAT to find out the
      structure(s) responsible for each DAT functions. DA uptake, MPP+ uptake, and
      cocaine binding in hDAT nearly disappeared only by the substitution of the 3rd
      transmembrane domain (TMD) with that of bDAT. On the contrary, the substitution
      of an identical region of hDAT into bDAT produced a complete shift toward the
      value of WT hDAT in the DA uptake, even though the MPP+ uptake and CFT binding
      maintained the values of WT bDAT. Collectively, these results suggest that the
      3rd TMD in DAT is crucial for the function, especially for DA uptake.

PMID- 9610362
TI  - Targeting human breast cancer cells that overexpress HER-2/neu mRNA by an
      antisense iron responsive element.
AB  - The overexpression of HER-2/neu proto-oncogene has been found in a variety of
      human cancers. In particular, the amplification and overexpression of HER-2/neu
      gene were found in 20-30% of breast and ovarian cancer patients with a decreased
      survival and an increased relapse rates. To target the breast cancer cells
      overexpressing HER-2/neu mRNA, a novel approach is described that combines the
      antisense principle and the biochemical property of a translation regulator, an
      iron responsive element (IRE). This report shows that a HER-2/neu antisense IRE
      reporter gene can be preferentially expressed in the breast cancer cells that
      overexpress HER-2/neu mRNA. This antisense IRE-mediated gene expression system
      may be applied broadly to target other cell type that uniquely expresses or
      overexpresses a known gene.

PMID- 9610363
TI  - Progesterone release of lipid second messengers at the amphibian oocyte plasma
      membrane: role of ceramide in initiating the G2/M transition.
AB  - Treatment with either sphingomyelinase (SMase), or soluble forms of ceramide, has
      been reported to induce meiosis in oocytes from Xenopus laevis, a species which
      can breed throughout most of the year. In this paper the sphingomyelin-derived
      second messenger, ceramide, is compared with progesterone for its ability to
      induce meiosis in oocytes from the seasonal breeder, Rana pipiens. Serum
      gonadotropin levels normally rise as Rana females emerge from hibernation in the
      spring, stimulating follicular synthesis of progesterone and subsequent
      ovulation. Injection of gonadotropins can induce earlier meiosis and ovulation,
      effective from the previous October through the following spring. During the same
      period, defolliculated oocytes respond to exogenous progesterone by meiosis, as
      indicated by nuclear breakdown. We find that in the spring, treatment of
      defolliculated Rana oocytes with exogenous C2- or C8-ceramide or SMase did induce
      meiosis, but not during the fall or winter. A 50% response was seen by late April
      and a 100% response by early May. Exposure of [3H]palmitate-labeled Rana oocytes
      to either exogenous progesterone or to SMase produced a rapid and comparable
      release of intracellular [3H]ceramide within 1-2 min in fall, winter or spring.
      Our results from this and from previous experiments indicate that increased
      ceramide is not the initiating event in meiotic induction in Rana, but is
      associated with a subsequent pathway which depends upon a threshold level of
      progesterone.

PMID- 9610364
TI  - Zinc suppresses apoptosis of U937 cells induced by hydrogen peroxide through an
      increase of the Bcl-2/Bax ratio.
AB  - Treatment of human premonocytic U937 cells with 500 microM H2O2 for 1h followed
      by 4h incubation in fresh medium to allow the cells to execute apoptotic
      processes caused DNA fragmentation. However, in the presence of 1mM ZnSO4
      throughout the incubation, DNA ladder formation was markedly inhibited. Hydrogen
      peroxide treatment for 1h with or without zinc increased both Bcl-2 and Bax
      proteins. However, only Bax protein decreased to basal levels in the presence of
      zinc during the following 4h incubation, resulting in an increase of the Bcl
      2/Bax ratio and prevention of apoptosis. Treatment of U937 cells with 1mM ZnSO4
      alone also decreased the levels of Bax protein. Furthermore, we observed that
      zinc completely inhibited the activation of CPP32 by H2O2, while no significant
      changes of ICE activities occurred with either H2O2 and/or zinc. These results
      indicate that the suppression of H2O2-induced apoptosis by zinc is mediated
      through an increase of the Bcl-2/Bax ratio, which occurs upstream from the
      activation of CPP32.

PMID- 9610365
TI  - Expression of peroxisome proliferator-activated receptor alpha (PPAR alpha) in
      primary cultures of human vascular endothelial cells.
AB  - The peroxisome proliferator-activated receptor (PPAR) is a member of the steroid
      nuclear receptor superfamily. Three types of PPARs have been described in humans:
      PPAR alpha, PPAR beta, and PPAR gamma. Here we investigated the levels of PPAR
      alpha mRNA in primary cultures of human umbilical venous endothelial cells
      (HUVEC), human umbilical arterial endothelial cells (HUAEC), human coronary
      arterial endothelial cells (HCAEC), and human aortic endothelial cells (HAEC),
      using the reverse transcriptase-polymerase chain reaction (RT-PCR). The HUVEC,
      HAEC, and HCAEC, but not the HUAEC, showed relatively low expression of PPAR
      alpha in comparison with liver, which was used as a positive control. Moreover,
      the partial sequences of the PCR-amplified products from HUVEC, HAEC, and HCAEC
      were similar to that of the PPAR alpha from human liver. The expression of PPAR
      alpha in cultured HAEC, which were induced by dexamethasone, was inhibited by
      insulin. In addition, PPAR alpha expression was also increased by benzafibrate or
      eicosapentaenoic acid with the physiological concentration. These results suggest
      that the PPAR alpha in endothelial cells may have the same physiological role as
      the expression of PPAR alpha in the liver.

PMID- 9610366
TI  - Differential effects of somatostatin and its analog on protein tyrosine kinases
      activity in the rat pituitary and the murine colonic tumors.
AB  - The effects of the native somatostatin-14 (SST-14) and of its analog octreotide
      (OCT) on the activity of protein tyrosine kinases (PTK) in the normal rat
      anterior pituitary gland, diethylstilbestrol (DES)-induced rat pituitary tumor
      and murine colonic cancer Colon 38 were studied in vitro. PTK activity was
      estimated in tissue homogenates using gamma-[32P]ATP and poly (Glu80, Tyr20) as a
      substrate. It was found that both SST-14 and OCT suppressed the PTK activity in
      all examined tissues. The suppressive effect was more pronounced in DES-induced
      pituitary tumor than in normal anterior pituitary gland, and in the former, OCT
      was more effective than SST-14. In contrast, SST-14 stronger suppressed PTK
      activity in colonic cancer than OCT. We hypothesize that SST-14 acts on PTK
      activity in colonic cancer mainly via SSTR-1 subtype of somatostatin receptors.

PMID- 9610367
TI  - Molecular cloning of Saccharomyces cerevisiae MLF4/SSH4 gene which confers the
      immunosuppressant leflunomide resistance.
AB  - Immunosuppressant leflunomide inhibits the growth of cytokine-stimulated lymphoid
      cells in vitro and also inhibits the growth of eukaryotic microorganism
      Saccharomyces cerevisiae. To elucidate the molecular mechanism of the action of
      the drug, a yeast gene which suppresses the anti-proliferative effect when in
      increased copy number was cloned and designated MLF4 for multicopy suppressor of
      leflunomide sensitivity. DNA sequencing analysis indicates that the MLF4 gene is
      identical to the SSH4 gene which suppresses the shr3 mutation. Excess of amino
      acids overcame the anti-proliferative activity of leflunomide. Thus, leflunomide
      is suggested to affect amino acid transport by interacting with Shr3 chaperon
      like protein.

PMID- 9610368
TI  - Cysteine protease inhibitor from pearl millet: a new class of antifungal protein.
AB  - A cysteine protease inhibitor exhibiting antifungal activity from pearl millet
      seeds has been purified to homogeneity by ammonium sulphate precipitation and
      chromatographic procedures involving CM- sephadex and SP-sepharose cation
      exchange columns. The molecular characterization has revealed its molecular mass
      as 24 kD and isoelectric point 9.8. The amino acid composition data shows
      presence of high content of serine and glycine (34 residues/mole) and absence of
      tryptophan. The inhibitor exhibits potent antifungal activity against Trichoderma
      reesei, a dead wood fungus with minimum inhibitory dose to inhibit mycelial
      growth or spore germination is as low as 1 microgram/ml (250 ng/disc). In
      addition to Trichoderma reesei, the antifungal activity is observed against some
      important phytopathogenic fungi, namely, Claviceps, Helminthosporium, Curvularia,
      Alternaria and Fusarium species. To the best of our knowledge, a cysteine
      protease inhibitor as an antifungal protein is reported for the first time from a
      plant system.

PMID- 9610369
TI  - Cloning and expression of a novel gene encoding a new antibacterial peptide from
      silkworm, Bombyx mori.
AB  - We differentially screened a novel gene encoding a new antibacterial peptide from
      the immunized Bombyx mori cDNA library. The gene showed a similar structure to
      that of cecropin-family, encoding 59 amino acids including a putative leader
      peptide and mature peptide. The deduced peptide, named Enbocin, had conserved
      amino acid residues which have been known to play an important role in the
      antibacterial activities. Enbocin genomic sequence revealed that the
      transcription unit of Enbocin gene was about 1.2 kb, and the coding sequence was
      interrupted by an intron of 660 bases. Recombinant Enbocin, expressed under the
      control of the baculovirus polyhedrin promoter, demonstrated a broad range of
      antibacterial activities against gram positive and gram negative bacteria.

PMID- 9610370
TI  - Cobalamin inhibition of HIV-1 integrase and integration of HIV-1 DNA into
      cellular DNA.
AB  - Our prior studies showed that certain cobalamins inhibit productive HIV-1
      infection of primary cultures of blood lymphocytes and monocytes. We demonstrate
      here that this antiviral activity may be mediated by an inhibition of HIV-1
      integrase, an enzyme required for productive infection. Purified recombinant HIV
      1 integrase activity was inhibited in vitro by hydroxocobalamin (OH-Cbl),
      methylcobalamin (Me-Cbl), adenosylcobalamin (Ado-Cbl), and dicyanocobinamide (CN2
      Cbi) with IC50 values of approximately 17, 17, 17, and 4 microM, respectively.
      The agents inhibited HIV-1 infection of cultured monocytes (IC50 values for OH
      Cbl, Me-Cbl, Ado-Cbl, and CN2-Cbi of 6, 7, 4, and 1 microM, respectively) and of
      cultured lymphocytes (IC50 values of 60, 50, 60, and 11 microM, respectively).
      Experiments using cultured monocytes or lymphocytes demonstrated that OH-Cbl
      inhibited integration of HIV-1 DNA into cellular DNA. Thus, cobalamins and
      cobinamides represent novel inhibitors of HIV-1 integrase. These or related
      agents may be useful as anti-viral treatments that target HIV-1 integrase.

PMID- 9610371
TI  - Glutathione homeostasis in human hepatic cells: overexpression of gamma
      glutamylcysteine synthetase gene in cell lines resistant to buthionine
      sulfoximine, an inhibitor of glutathione synthesis.
AB  - The synthesis of glutathione (GSH) and its conjugation to xenobiotics are
      essential for detoxification in liver cells. To understand how cellular levels of
      GSH are balanced in response to environmental stress, we cloned two cell lines,
      HLE/BSO1-1 and HLE/BSO1-2, from human hepatic HLE/WT cells resistant to
      buthionine sulfoximine (BSO), an irreversible inhibitor of gamma-glutamylcysteine
      synthetase (GCS). HLE/BSO1-1 and HLE/BSO1-2 showed 35- and 40-fold higher
      resistance respectively, than the wild type to BSO. In the absence of BSO,
      cellular levels of GSH were 3.0-fold higher, whereas levels of Pi class
      glutathione thiol transferase, GSTP1, were 2-fold lower, in the subclones than in
      the wild type cells. GCS heavy subunit (GCSh) mRNA level were 2.5-fold higher in
      HLE/BSO1-1 and HLE/BSO1-2 as compared with HLE/WT. Sequences between -315 and 
      241 base pairs of the 5' region, which contain an AP1 site, were shown to be
      responsible for the enhanced expression of GCSh in HLE/BSO1-1 cells. The
      expression of a dominant-negative mutant of c-Jun was found to inhibit the AP1
      dependent GCSh promoter activity in HLE/WT and HLE/BSO1-1. Both protein level of
      c-Jun and binding activity of AP-1 were increased in both HLE/BSO1-1 and HLE/BSO1
      2 cells. The up-regulation of GCSh gene appeared to be due to enhanced GCSh
      promoter acting through AP-1 activation in BSO-resistant hepatic cells.

PMID- 9610372
TI  - Mechanotransduction in stretched osteocytes--temporal expression of immediate
      early and other genes.
AB  - Osteocytes, dendritic bone cells, transduce signals of mechanical loading that
      results in bone formation. We have reported in stretched primary osteocytes that
      the cAMP level, IGF-I and osteocalcin protein levels were elevated (Endocrinology
      137:2028, 1996). Here we report that stretching induces the expression of
      immediate early genes, c-fos, and COX-2; inducive cyclooxygenase gene. Compared
      to c-fos, COX-2 as well as IGF-I and osteocalcin mRNA appeared in a biphasic
      manner; second peaks at 8 (COX-2) or 24 hrs (IGF-I and osteocalcin) later.
      Furthermore, these second peaks are abolished by including NS398, a specific
      inhibitor of the inducive cyclooxygenase, during the 3-hr stretching. A sequence
      that the calcium influx activates PkA which, in turn, activates c-fos and COX-2
      transcription resulting in the production of proteins such as IGF-I and
      osteocalcin. A long-lasting effect of mechanical loading in vivo can be explained
      from the secondary anabolic reaction we observed through the upregulated COX-2
      mRNA.

PMID- 9610374
TI  - Increased plasma P-selectin induced by intravenous administration of endotoxin in
      rats.
AB  - We developed a competitive enzyme immunoassay for detection of rat P-selectin and
      examined temporal changes of plasma P-selectin levels in an endotoxin-induced
      injury model in rats. Soluble P-selectin was detected in rat plasma after
      intravenous administration of lipopolysaccharide (LPS), and increased to a
      maximum level of five-fold over baseline after 24 hours. Plasma P-selectin was
      partially purified by gelfiltration and was identified as a 122 kDa band by
      Western blotting. Using the ELISA system we developed, monitoring of plasma P
      selectin has become possible in the rat.

PMID- 9610373
TI  - Enzymatic activation of immunoglobulin binding factor in female reproductive
      tract.
AB  - Human seminal plasma and cervical mucus contains an immunoglobulin binding factor
      (IgBF) which interacts with IgG as monomers under reducing condition. It may play
      a role in preventing antibody production against allogeneic sperms in the female
      reproductive tract. However, since IgBF is secreted as a homodimer that does not
      bind IgG, in vivo activation systems should be investigated. GSH reduces the
      inactive native dimer to the active monomer. Protein disulfide isomerase (PDI), a
      molecular chaperone, alters the configuration of dimers to active monomers. 20S
      proteasomes produced by activated T cells which cleave the dimers in the presence
      of GSH to active fragments. All these activating systems are widely distributed
      as cellular enzymes in vivo. Also PDI mRNAs are expressed in uterine cervix,
      endometrium and fallopian tube. Since these enzymes are produced upon stimulation
      by the immune system, we hypothesize that immunocompetent cells interact with
      allogeneic sperms, leading to the local production of these enzymes that will
      activate IgBF.

PMID- 9610375
TI  - AP-1 and ATF-2 are constitutively activated via the JNK pathway in Theileria
      parva-transformed T-cells.
AB  - Bovine T-cells infected by the protozoan parasite Theileria parva undergo
      lymphoblastoid transformation, and proliferate in an uncontrolled manner. While
      it has been established that the transcription factor NF-kappa B is
      constitutively activated in T. parva-infected T-cells, little is known about
      other transcription factors such as AP-1 and ATF-2. We demonstrated increased
      binding activity to the AP-1 and CREB/ATF-2 consensus binding sites and show that
      the AP-1 complex is composed of c-Jun, JunD, c-Fos, and ATF-2. The transcription
      factors c-Jun and ATF-2 are constitutively phosphorylated in a parasite-dependent
      manner. Both transcription factors can be phosphorylated by jun-NH2-terminal
      kinase (JNK), but ATF-2 is also a substrate for p38. We determined whether p38 is
      activated in T. parva-infected cells. Immunoblot analysis and inhibitor studies
      indicate that JNK, but not p38, is involved in ATF-2 phosphorylation. Based on
      these results and previous studies, we conclude that parasite interference with
      mitogen-activated protein kinase pathways is restricted to constitutive
      activation of JNK.

PMID- 9610376
TI  - Cyclic AMP induces ryanodine-sensitive Ca2+ release from microsomal vesicles of
      rat parotid acinar cells.
AB  - The effect of cAMP on a ryanodine-sensitive Ca2+ release from microsomal vesicles
      of rat parotid acinar cells was studied. After a steady state of ATP-dependent
      45Ca2+ uptake into the vesicles, cAMP was added to the medium with thapsigargin
      (TG) to block a reuptake of 45Ca2+. The addition of cAMP (1.0 mM) with TG
      released about 10% of the 45Ca2+ that had been taken up. The cAMP-induced 45Ca2+
      release was strongly inhibited by pretreatment of the vesicles with 500 microMM
      ryanodine. Preincubation with cAMP (1 mM) abolished ryanodine (10 microM)-induced
      45Ca2+ release. The presence of a specific inhibitor of cAMP-dependent protein
      kinase (PKA) H-89 (10 microMM) inhibited the cAMP-induced 45Ca2+ release. These
      results indicate that in rat parotid acinar cells, cAMP can activate a ryanodine
      sensitive Ca2+ release mechanism in the endoplasmic reticulum and that this
      activation is via a PKA-dependent process.

PMID- 9610377
TI  - Insulin and insulin-like growth factor-I receptor mediated differentiation of 3T3
      F442A cells into adipocytes: effect of PI 3-kinase inhibition.
AB  - The ability of insulin and insulin-like growth factors (IGF-I and IGF-II) to
      induce differentiation of 3T3-F442A cells into adipocytes was examined at various
      hormone concentrations. Both insulin and the IGFs promoted differentiation at
      concentrations compatible with binding to their cognate receptors, suggesting
      that both insulin and IGF-I receptors are capable of promoting this
      differentiation. Adipocyte conversion of 3T3-F442A cells was completely blocked
      in the presence of LY294002, a specific inhibitor of PI 3-kinase, indicating that
      PI 3-kinase activity plays a crucial role in the initial signalling events that
      trigger this differentiation process.

PMID- 9610378
TI  - Methylesters of L-arginine and N-nitro-L-arginine induce nitric oxide synthase in
      Staphylococcus aureus.
AB  - The presence of L-arginine methylester (AME), L-arginine ethylester (AEE), or N
      nitro-L-arginine methylester (NAME) in the growth media of Staphylococcus aureus
      increased the nitric oxide synthase (NOS) activity approximately 5- to 14-fold.
      The increase of NOS activity was confirmed by two assay methods, namely assaying
      the formation of L-[3H] citrulline from L-[3H] arginine and NO formation. The
      increase of NOS activity was most likely due to increased de novo synthesis,
      demonstrated by Western immunoblot analysis. The addition of methanol to the
      culture medium also increased the NOS activity as much as that found with the
      above three compounds. Evidence is presented to show that AME, AEE, or NAME gave
      rise to the formation of methanol in vivo by the action of intracellular
      esterase(s) and that methanol is subsequently involved in the induction of NOS in
      this bacterial system.

PMID- 9610379
TI  - Common proteins bind mRNAs encoding erythropoietin, tyrosine hydroxylase, and
      vascular endothelial growth factor.
AB  - The hypoxia-inducible genes erythropoietin (Epo), tyrosine hydroxylase (TH), and
      vascular endothelial growth factor (VEGF) are regulated post-transcriptionally by
      proteins binding to specific regions located in the 3' untranslated region (UTR)
      of their mRNAs. To determine whether trans-factors binding to this region in all
      three of these RNAs are similar, we generated riboprobes containing the 3' UTR of
      erythropoietin, tyrosine hydroxylase, and vascular endothelial growth factor mRNA
      and assayed them by electrophoretic mobility shift assay (EMSA) and UV cross
      linking experiments. Each riboprobe formed similar shifted protein complexes
      using human hepatoma cell (Hep3B) cytoplasmic lysates in the EMSA. Hep3B proteins
      bound to each probe could be cross-competed by the specific unlabeled Epo, TH, or
      VEGF riboprobes. By contrast, a non-specific 3' UTR riboprobe did not compete for
      binding with the Epo, TH, or VEGF RNA shifted protein complexes. UV cross-linking
      studies revealed proteins of similar molecular weights for the Epo, TH, and VEGF
      RNA shifted protein complexes. Taken together, these results suggest a common
      posttranscriptional regulatory mechanism for hypoxia-inducible genes.

PMID- 9610380
TI  - Intermolecular interaction of lens crystallins: from rotationally mobile to
      immobile states at high protein concentrations.
AB  - The conformation of lens crystallins in vivo or in a highly concentrated solution
      is not well established. Most studies were carried out in dilute solutions in
      which protein-protein interaction is minimal. In order to see whether there is
      conformational change (tertiary and secondary structures) when crystallin
      solutions are brought to high concentrations, we have performed the following
      molecular spectroscopic measurements: circular dichroism (CD) and Fourier
      transform infrared (FTIR). Near-UV CD measurements showed a more than two-fold
      increase in CD intensity (molar ellipticity) for the total water-soluble (WS)
      protein from young calf lens nucleus in a highly concentrated solution (> 300
      mg/ml in a 0.01-mm cell), when compared with a dilute solution (1000-fold
      dilution in a 10-mm cell). The individual crystallins in concentrated solutions
      also showed an increase in CD intensity, but of different magnitude: alpha
      crystallin > beta-crystallin > gamma-crystallin. The increased CD indicates that
      lens crystallins are in a more compact structure in highly concentrated
      solutions; they likely undergo a transition from a mobile to an immobile state.
      Change in near-UV CD usually is caused by restricted mobility of aromatic side
      groups, particularly Trp. The transition involves not only a change in protein
      tertiary and/or quaternary structure, but also in protein backbone structure. The
      change of protein backbone structure was drawn from FTIR measurements. FTIR
      spectra, sensitive to the secondary structure in the amide I region, could be
      measured for a highly concentrated solution for which far-UV CD measurement is
      not feasible. The secondary structure that showed prominent change for alpha
      crystallin in a highly concentrated solution was beta-conformation: increase in
      beta-turn with a concomitant decrease of alpha-helix structure.

PMID- 9610381
TI  - Characteristic analysis of the luxG gene encoding the probable flavin reductase
      that resides in the lux operon of Photobacterium leiognathi.
AB  - Nucleotide sequence of the luxG gene (GenBank Accession No. AF053227) from
      Photobacterium leiognathi PL741 has been determined, and the encoded probable
      flavin reductase is deduced. The probable flavin reductase encoded by the luxG
      gene has a calculated M(r) 26,544 and comprises 235 amino acid residues. The
      probable flavin reductase like the NAD(P)H-flavin reductase might catalyze the
      reduction of flavins. Alignment and comparison of the probable flavin reductases
      from P. leiognathi PL741, ATCC 25521, P. phosphoreum, Vibrio fischeri, and V.
      harveyi show that they are homologous; there is 66% homologous (29.4% identity
      and 36.6% similarity). Also, the probable flavin reductase is homologous to the
      NAD(P)H-flavin reductase; it is perceived that the probable flavin reductase and
      the NAD(P)H-flavin reductase could be enzyme isoforms encoded by two genes of a
      multigene family for differential response functions. Functional analysis
      illustrates that the specific segment sequence lay inside and behind the luxG
      gene might form the potential hairpin loops omega gI, omega gII, omega o, and
      omega oT as mRNA stability loop or/and as the attenuator-like loop or the dynamic
      terminator-like block for sub-regulation in the lux operon. The gene order of the
      luxG gene in the lux operon and the lum operon is <--ter-lumQ-lumP-R&R-luxC-luxD
      luxA-luxB-+ ++luxN-luxE-luxG--> (R&R: regulatory region; ter: transcriptional
      terminator), whereas the R&R is the regulatory region for the lum operon and the
      lux operon, and ter is the transcriptional terminator for the lum operon.

PMID- 9610382
TI  - Effect of gabexate mesylate (FOY), a drug for serine proteinase-mediated
      diseases, on the nitric oxide pathway.
AB  - Considering the structural similarity between gabexate mesylate (FOY), a drug for
      serine proteinase-mediated diseases, and L-arginine, the effect of gabexate
      mesylate on the nitric oxide (NO) pathway has been investigated. Gabexate
      mesylate inhibits competitively constitutive and inducible NO synthase (cNOS and
      iNOS, respectively), with Ki values of 1.0 x 10(-4) M and 5.0 x 10(-3) M,
      respectively, at pH 7.4 and 37.0 degrees C. However, gabexate mesylate is not an
      NO precursor. Moreover, like other NOS inhibitors, gabexate mesylate increases
      iNOS mRNA expression in rat C6 glioma cells, as induced by E. coli
      lipopolysaccharide plus interferon-gamma. Finally, gabexate mesylate inhibits
      dose-dependently nitrite production (i.e. NO release) in rat C6 glioma cells, as
      induced by E. coli lipopolysaccharide plus interferon-gamma. Thus, this drug
      should be administered under careful control, since enzyme inhibition may occur
      also in vivo.

PMID- 9610383
TI  - Purification of toxic compounds from larvae of the gray fleshfly: the
      identification of paralysins.
AB  - Larval haemolymph of Neobellieria bullata (Insecta, Diptera) is highly toxic to
      adults of the same species: injection causes instant paralysis to death.
      Referring to their dramatic effect in adult insects the responsible compounds
      were designated paralysins. Two paralysins, soluble in organic solvents and heat
      stable, were chromatographically purified to homogeneity. They were identified by
      use of mass spectrometry and nuclear magnetic resonance respectively as beta
      alanine-tyrosine (beta-Ala-Tyr) and as 3-hydroxy-kynurenine (3-HK). The
      quantities of beta-Ala-Tyr and 3-HK in the insect appear to increase steadily
      during larval development, with peak values prior to the pupal stage. These
      findings may contribute to a better understanding of some aspects of the process
      of insect metamorphosis. Orienting experiments in mammals suggest that both
      compounds, when injected intraspinally, are also neurotoxic to rats. In addition,
      cytotoxicity tests revealed that 3-HK, but not beta-Ala-Tyr is toxic to human
      neuroblastoma cells, rat primary cortex neurons as well as to rat glial cells.

PMID- 9610384
TI  - Stimulation of prohormone convertase-1 mRNA expression by second messenger
      signaling systems.
AB  - The purpose of this study was to investigate the effects of activation of various
      second messenger signaling systems on gene expression (i.e. mRNA levels) of a
      peptide hormone processing enzyme called prohormone convertase-1 (PC-1, also
      called PC-3) in a human pancreatic carcinoid cell line (BON) that expresses
      several endocrine peptides (chromogranin A, pancreastatin, neurotensin).
      Pharmacologic activation of adenylate cyclase-cAMP, protein kinase-C and Ca2+
      mobilization pathways increased PC-1 mRNA levels and neurotensin secretion.
      Elevations in PC-1 mRNA levels were dose and time-related. Secretagogue-induced
      cellular depletion of neurotensin was followed by a replenishment of cellular
      neurotensin stores and an upregulation of PC-1 mRNA levels. Together, these data
      indicate that PC-1 mRNA expression is increased with peptide secretion and
      coordinated with maintenance of cellular stores of peptides.

PMID- 9610385
TI  - A highly active microsomal glutathione transferase from frog (Xenopus laevis)
      liver that is not activated by N-ethylmaleimide.
AB  - Microsomal glutathione transferase has hitherto only been purified from mammalian
      species. N-ethylmaleimide and trypsin activation (discriminating features of this
      enzyme) has only been observed in microsomes from mammals. In this paper we
      describe the first isolation and characterization of a non-mammalian microsomal
      glutathione transferase from frog (Xenopus laevis) liver. This protein has a
      molecular weight similar to that of the mammalian enzyme (approximately 17 kDa),
      but cannot be activated by N-ethylmaleimide or trypsin. In fact the enzyme is
      rapidly inactivated by this sulfhydryl reagent and protease. It thus appears that
      N-ethylmaleimide activation is not an obligatory property of microsomal
      glutathione transferase. The frog liver microsomal glutathione transferase has
      one of the highest specific activities towards the second substrate 1-chloro-2,4
      dinitrobenzene (CDNB) (200 mumol/min mg) obtained with any glutathione
      transferase and accounts for the high activity found in frog liver microsomes.
      The kcat/K(m) for glutathione and CDNB are 0.017 and 1.1 x 10(6) M-1 s-1,
      respectively. The enzyme also functions as a glutathione peroxidase (dilinoleoyl
      phosphatidylcholine hydroperoxide is reduced (5.2 mumol/min mg)). It is now
      evident that a highly active microsomal glutathione transferase, with a molecular
      weight similar to that of the mammalian enzymes also exists in a non-mammal
      species.

PMID- 9610386
TI  - Valacyclovir: a substrate for the intestinal and renal peptide transporters PEPT1
      and PEPT2.
AB  - Valacyclovir is a prodrug of the antiviral agent acyclovir and it does not
      contain a peptide bond in its structure. We studied the interaction of
      valacyclovir with the peptide transporters in the human intestinal cell line Caco
      2 and the rat kidney proximal tubular cell line SKPT which differentially express
      peptide transporters PEPT1 and PEPT2. The results of the studies done with these
      cell lines were confirmed with the cloned peptide transporters human PEPT1 and
      rat PEPT2, expressed heterologously in HeLa cells. The activity of the peptide
      transporters was assessed by measuring the uptake of radiolabeled glycylsarcosine
      in the presence of a H+ gradient. Valacyclovir inhibited the uptake of
      glycylsarcosine with an inhibition constant (Ki) of 0.49 +/- 0.04 mM in Caco-2
      cells and 0.17 +/- 0.01 mM in SKPT cells. In both cell types, the inhibition was
      competitive. Acyclovir, in contrast to valacyclovir, did not interact with the
      peptide transporters. Similar results were obtained with heterologously expressed
      human PEPT1 and rat PEPT2. Valacyclovir inhibited the hPEPT1-mediated
      glycylsarcosine transport competitively with a Ki value of 0.74 +/- 0.14 mM. The
      rPEPT2-mediated transport of glycylsarcosine was also inhibited by valacyclovir
      competitively and the Ki value for the process was 0.39 +/- 0.03 mM. Acyclovir
      did not interact with either of these cloned peptide transporters. We conclude
      that valacyclovir is a substrate for the peptide transporters PEPT1 and PEPT2 and
      that a peptide bond is not a prerequisite for recognition as a substrate by the
      peptide transporters.

PMID- 9610387
TI  - Induction of apoptosis in pancreatic acinar cells reduces the severity of acute
      pancreatitis.
AB  - 1-Cyano-2-hydroxy-3-butene (CHB) has been reported to cause cell death in rat
      pancreatic acini. In this report, we describe the time-dependent effects of CHB
      on mouse acinar cell apoptosis and the effects of CHB-induced acinar cell
      apoptosis on the severity of secretagogue-induced acute pancreatitis in mice. CHB
      administration to mice resulted in a time-dependent increase in pancreatic
      apoptosis, which was maximal 12 hours after CHB administration. The severity of
      pancreatitis was significantly reduced by prior CHB administration and maximal
      protection was observed when the caerulein injections were started 12 hours after
      CHB administration. These observations indicate that induction of apoptosis can
      reduce the severity of pancreatitis and they suggest that induction of pancreatic
      acinar cell apoptosis may be beneficial in the clinical management of acute
      pancreatitis.

PMID- 9610388
TI  - Involvement of Bcl-2 cleavage in the acceleration of VP-16-induced U937 cell
      apoptosis.
AB  - Apoptosis is cellular suicide functionally opposite of mitosis. It plays an
      important role in tissue growth control and removal of damaged and premalignant
      cells. The decrease in death suppressor Bcl-2 protein level was implicated in the
      many types of apoptotic cell death. Because Bcl-2 protein was recently found to
      be cleaved during apoptosis induced by Fas ligation, IL-3 withdrawal, and
      alphavirus infection, we assessed whether Bcl-2 protein was also cleaved during
      the anticancer drug (VP-16)-induced apoptotic cell death in U937 cells. We found
      that Bcl-2 protein was cleaved in vivo and in vitro after the treatment of VP-16.
      We also found that caspase-3/CPP32, which was activated after VP-16 treatment,
      was responsible for the direct cleavage of Bcl-2 protein. The overexpression of
      the cleaved Bcl-2 fragment increased the sensitivity to VP-16 and promoted
      apoptotic cell death. Therefore, caspase-3/CPP32 accelerates VP-16-induced U937
      cell apoptosis by cleaving death suppressor Bcl-2 protein to produce a death
      promoter Bcl-2 fragment.

PMID- 9610389
TI  - Characteristics of smooth muscle cell lipoprotein binding proteins (p105/p130) as
      T-cadherin and regulation by positive and negative growth regulators.
AB  - Smooth muscle cells (SMC) express atypical surface low density lipoprotein (LDL)
      binding proteins of M(r)105 and M(r)130 (p105 and p130) which have been
      putatively identified as the cell adhesion glycoprotein T-cadherin. Using
      cultured human and rat aortic SMC and analysis by ligand (LDL)- and immuno
      blotting techniques we now confirm identity of p105 and p130 as T-cadherin, as
      adjudged by sensitivity to PI-PLC cleavage, insensitivity to trypsin degradation
      in the presence of calcium, and immunoreactivity to anti-T-cadherin peptide
      antisera. The function of T-cadherin (p105/p130) in the vasculature is unknown.
      The proteins were downmodulated by the peptide growth factors PDGF-BB, IGF, EGF,
      and bFGF, but not by vasoactive peptide hormones (angiotensin II, vasopressin,
      bradykinin, and endothelin). TGF beta, a recognized inhibitor of SMC
      proliferation, per se had no effect but inhibited growth factor-induced p105/p130
      downmodulation. Expression of p105/p130 in quiescent SMC and growth-stimulated
      SMC (respectively, in serum-free and serum or PDGF-BB containing culture
      conditions) was increased by forskolin and 8-Br-cyclic GMP, both anti-mitogenic
      substances, but was unaffected by phorbol ester, calcium ionophores, or calcium
      antagonists. The findings are compatible with a function for the lipoprotein
      binding proteins (T-cadherin) in negative regulation of SMC growth.

PMID- 9610390
TI  - Functional role for glycosylated subtypes of rat endothelin receptors.
AB  - Glycosylation of endothelin (ET) receptors was found to occur in rat cerebellar
      and atrial membranes. Specifically, we investigated whether the ETA and ETB
      receptor subtypes differed in their sensitivity to deglycosylation treatment and
      whether the two affinity states (nanomolar and picomolar) observed in each
      receptor subtype reflect differences in glycosylation states. Pretreatment of
      cerebellar or atrial membranes with endoglycosidase H (endo H) caused a marked
      decrease in the number of maximal binding sites that bind ligand with nanomolar
      affinity, whereas ligand affinity remained the same. The picomolar-affinity
      binding sites were not affected by endo H. The use of specific antagonists
      indicated that the receptor subtype most likely to be influenced by glycosylation
      is ETA. We suggest that in both cerebellar and atrial membranes, the carbohydrate
      chains of the ETA receptor contribute to the binding of ligand to the nanomolar
      affinity binding sites, but not to the picomolar-affinity binding sites.

PMID- 9610391
TI  - Expression of extracellular calcium (Ca2+o)-sensing receptor in human peripheral
      blood monocytes.
AB  - The calcium-sensing receptor (CaR) is a G protein-coupled receptor playing key
      roles in extracellular calcium ion (Ca2+o) homeostasis in parathyroid gland and
      kidney. Macrophage-like mononuclear cells appear at sites of osteoclastic bone
      resorption during bone turnover and may play a role in the "reversal" phase of
      skeletal remodeling that follows osteoclastic resorption and precedes
      osteoblastic bone formation. Bone resorption produces substantial local increases
      in Ca2+o that could provide a signal for such mononuclear cells present locally
      within the bone marrow microenvironment. Indeed, previous studies by other
      investigators have shown that raising Ca2+o either in vivo or in vitro stimulated
      the release of interleukin-6 (IL-6) from human peripheral blood monocytes,
      suggesting that these cells express a Ca2+o-sensing mechanism. In these earlier
      studies, however, the use of reverse transcription-polymerase chain reaction (RT
      PCR) failed to detect transcripts for the CaR previously cloned from parathyroid
      and kidney in peripheral blood monocytes. Since we recently found that non
      specific esterase-positive, putative monocytes isolated from murine bone marrow
      express the CaR, we reevaluated the expression of this receptor in human
      peripheral blood monocytes. Immunocytochemistry, flow cytometry, and Western blot
      analysis, performed using a polyclonal antiserum specific for the CaR, detected
      CaR protein in human monocytes. In addition, the use of RT-PCR with CaR-specific
      primers, followed by nucleotide sequencing of the amplified products, identified
      CaR transcripts in the cells. Therefore, taken together, our data show that human
      peripheral blood monocytes possess both CaR protein and mRNA very similar if not
      identical to those expressed in parathyroid and kidney that could mediate the
      previously described, direct effects of Ca2+o on these cells. Furthermore, since
      mononuclear cells isolated from bone marrow also express the CaR, the latter
      might play some role in the "reversal" phase of bone remodeling, sensing local
      changes in Ca2+o resulting from osteoclastic bone resorption and secreting
      osteotropic cytokines or performing other Ca2+o-regulated functions that
      contribute to the control of bone turnover.

PMID- 9610392
TI  - Propensity for macrophage apoptosis is related to the pattern of expression and
      function of integrin extracellular matrix receptors.
AB  - Ligation of integrins to an extracellular matrix activates signal transduction
      systems which produce multiple responses in different cell types. Adhesion often
      provides a survival signal to cells; disruption of adhesion frequently results in
      apoptosis. Our laboratory has utilized apoptosis-sensitive and -resistant cell
      lines to investigate the role of integrin expression and function in regulation
      of apoptosis in macrophages. Chronic exposure of murine macrophage-like RAW264.7
      cells to apoptosis-inducing agents (bacterial lipopolysaccharide and interferon
      gamma) resulted in the generation of a derivative cell line (RES) resistant to
      apoptosis. Observation of RAW and RES cultures indicated a difference in adhesion
      between the two cell types. The two cell lines also exhibit significant
      differences in expression of integrins previously characterized to be important
      in apoptosis.

PMID- 9610393
TI  - Pancreatic lipase-related protein type 1: a double mutation restores a
      significant lipase activity.
AB  - Besides the active pancreatic lipase (PL) which plays a major role in dietary fat
      digestion, the presence of a pancreatic lipase related protein 1 (PLRP1)
      displaying a very low lipolytic activity has been reported in vertebrates. It has
      been suggested that the reduced lipolytic activity of PLRP1 results from specific
      features of the N-terminal domain of the protein. Therefore, based on sequence
      comparison between PL and PLRP1 and modelling experiments, several residues
      located in the vicinity of the active site pocket of both enzymes have been
      mutated. In this paper, we report that, as regards to PL, two substitutions in
      positions 179 and 181 in PLRP1 account for the very low lipolytic activity of the
      protein. Indeed, substituting these residues (V179 and A181) in PLRP1 for those
      found in PL (A179 and P181), restores a significant lipolytic activity for PLRP1.

PMID- 9610394
TI  - Assembled IgG molecules are exported from the endoplasmic reticulum in myeloma
      cells despite the retention signal SEKDEL.
AB  - The KDEL retention signal, when added at the C-terminal of the constant region of
      light and heavy chains of immunoglobulins is able to efficiently retain assembled
      immunoglobulins only in cells of nonlymphoid origin. In transfected myeloma cells
      the wild type and the KDEL-Ig mutants are secreted with the same efficiency. This
      phenomenon is not due to a proteolytic cleavage of the KDEL signal nor to a lack
      of intermolecular disulfide bond formation and is not due to an impaired
      recognition of the KDEL signal in myeloma cells. Thus, the constitutive secretion
      of assembled immunoglobulins, currently considered to follow a default process,
      appears to be regulated by a mechanism that is able to overcome an efficient ER
      retention system.

PMID- 9610395
TI  - Novel transcriptional mechanisms are involved in regulating preproenkephalin gene
      expression in vivo.
AB  - For the dissection of the temporal and spatial patterns of cell- and tissue
      specific gene expression an understanding of the contributing regulating
      mechanisms is required. We now confirm that there are novel mechanisms regulating
      preproenkephalin gene expression in basal as well as cholinergic agonist treated
      rats. Moreover, we demonstrate that these novel transcriptional mechanisms are
      consistent with RNA intragenic elongation pausing, alternate promoter usage, and
      small sense and antisense RNA transcription from the preproenkephalin gene locus.
      We report that while basal striatal and olfactory bulb proenkephalin RNA
      transcripts are initiated from the "normal" proximal promoter, in cerebellum de
      novo RNA transcription appears to be initiated from the distal so-called "germ
      cell" promoter. Furthermore, "normally" initiated olfactory bulb proenkephalin
      RNA transcripts appear to be down-regulated by the time the RNA polymerase II
      complex reaches the first preproenkephalin intron, in a way that is consistent
      with RNA elongation pausing. As the pattern of small sense and antisense
      transcripts found associated with this gene's expression is tissue-specific, we
      suggest that they may also play a role in regulating gene expression. The
      understanding of this gene's regulation should have widespread importance, not
      only to those interested in opioid gene expression, but also to those interested
      in gene regulation, in general.

PMID- 9610396
TI  - A novel unusual DNA structure formed in an inverted repeat sequence.
AB  - A potential to form a non-cruciform unusual DNA structure was shown at the
      inverted repeat DNA sequence of a fish satellite DNA. The recombinant plasmid
      harboring a member of the EcoRI satellite family of Sillago japonica (Percoidei,
      Sillaginidae) was subjected to S1 nuclease treatment, and the cutting sites were
      mapped by primer extension assay. The S1 nuclease attacked the 3'-half of the
      inverted repeat but not the middle part of symmetry under various salt
      conditions, suggesting that this unusual DNA structure is different from the DNA
      cruciform and a conventional intramolecular triplex structure. In the presence of
      200 mM potassium chloride, the typical DNA cruciform has extruded, suggesting
      that certain purine-purine-pyrimidine base triads are involved in the formation
      of this unusual DNA structure. These results support the occurrence of a novel
      unusual DNA structure formed in the inverted repeat sequence.

PMID- 9610397
TI  - Molecular cloning of a new sodium bicarbonate cotransporter cDNA from human
      retina.
AB  - Sodium bicarbonate cotransport is an electrogenic process and a principal
      regulator of pH. A recently cloned sodium bicarbonate cotransporter (NBC1) is
      predominantly expressed in kidney. The presence of several isoforms is suggested
      from functional studies. We have cloned a new member of this family from human
      retina, which was named hNBC2 (for human sodium bicarbonate cotransporter 2). The
      hNBC2 has 1018 amino acid residues with 10 hydrophobic transmembrane domains. A
      cluster of five N-glycosylation sites is present at the second extracellular
      loop. It has 53% amino acids identity with hNBC1 and 38% identity with anion
      exchanger 1. Thus, NBC2 is a new member of the anion exchanger superfamily.
      Northern blot of human tissues revealed its expression in many tissues such as
      testis, spleen, ovary, small intestine, colon, thymus, heart, and muscle (8.5
      kb). The predominant expression at retina was documented with Northern blot of
      rat tissues. NBC2 may be a major regulator of extracellular pH of retina where
      light stimulation produces an extracellular alkalization and may contribute as a
      solute transporter to the prevention of retinal detachment.

PMID- 9610398
TI  - Evidence for bidirectional functional communication between myosin subfragments 1
      and 2 in skeletal muscle fibers.
AB  - It has been shown that, in glycerinated skeletal muscle fibers, polyclonal
      antibody directed against myosin subfragment 2 (S-2) eliminates Ca(2+)-activated
      isometric force development, while Mg-ATPase activity of the fibers remains
      unchanged. To further explore possible involvement of myosin S-2 in muscle
      contraction, we studied the effect of anti-S-2 antibody on rigor linkage
      formation in the fibers. It was found that the antibody inhibited development of
      rigor force in a dose- and time-dependent manner, without changing the relation
      between muscle fiber stiffness and force. If, however, the antibody was applied
      after development of rigor force, it had no effect on both the stiffness and
      force. These results strongly suggest bidirectional functional communication
      between myosin subfragments 1 and 2 in the fibers.

PMID- 9610399
TI  - Evidence for mitochondrial Ca(2+)-induced Ca2+ release in permeabilised
      endothelial cells.
AB  - Generally most intracellular Ca2+ is stored in the endoplasmic reticulum (ER) and
      mitochondria. Recently a mitochondrial Ca(2+)-induced Ca2+ release (mCICR)
      mechanism, unconnected with ryanodine receptors (RyR's), has been shown in tumour
      cells. The existence of a mitochondrial Ca2+ release mechanism in BAE cells was
      investigated using saponin-permeabilised BAE cells. When buffered intracellular
      solution were 'stepped' from 10 nM to 10 microM free Ca2+, the mitochondrial
      inhibitors CN (2 mM), FCCP (1 microM), and RR (20 microM) significantly reduced
      total CICR by approximately 25%. The ER Ca(2+)-ATPase inhibitor thapsigargin (100
      nM) had no effect. Furthermore, cyclosporin A (200 nM), an inhibitor of the
      mitochondrial permeability transition pore (PTP), abolished total CICR.
      Therefore, the novel ryanodine-caffeine insensitive CICR mechanism previously
      reported in BAE cells involves mitochondrial Ca2 release. It is proposed that in
      BAE cells, mCICR occurs via the mitochondrial PTP and may be physiologically
      important in endothelial cell Ca2+ signalling.

PMID- 9610400
TI  - Essential role of phosphatidylserine externalization in apoptosing cell
      phagocytosis by macrophages.
AB  - In many apoptotic cells, phosphatidylserine (PS), that is normally restricted to
      the inner membrane layer, is externalized and subsequently recognized by
      phagocytes. However, it has been unclear whether PS externalization is sufficient
      for phagocytosis induction. In a cultured cell line undergoing Fas-mediated
      apoptosis, PS externalization preceded other apoptotic events. When transbilayer
      movement of membrane phospholipids was analyzed, a decrease of the uptake of PS
      and phosphatidylethanolamine and an increase of phosphatidylcholine incorporation
      were observed upon apoptosis induction. Apoptotic cultured cells were
      phagocytosed by macrophages in a manner dependent on externalized PS before
      plasma membrane permeability increased. Moreover, a N-ethylmaleimide treatment
      caused PS externalization independent of apoptosis, and such cells underwent PS
      mediated phagocytosis. These results suggested that PS is externalized as a
      result of membrane phospholipid redistribution and externalized PS by itself
      induces apoptosing cell phagocytosis.

PMID- 9610401
TI  - Mitochondrial membrane potential supported by exogenous cytochrome c oxidation
      mimics the early stages of apoptosis.
AB  - Mitochondria isolated from rat liver, incubated with inhibitors of respiratory
      Complexes I and III but in the presence of added NADH as a source of reducing
      equivalents, generate a membrane potential, the extent of which is comparable to
      that supported by the oxidation of intramitochondrial respiratory substrates. A
      catalytic amount of exogenously added cytochrome c is required in order for this
      membrane potential to be observed. Such an experimental approach mimics the early
      stages of the apoptotic program of mammalian cells. This has been reported to be
      characterized by the extrusion of the bulk of intermembrane pool of cytochrome c
      while the mitochondria continue to preserve their membrane potential. The data
      obtained are consistent with the proposal that the bi-trans-membrane electron
      transport pathway, activated by the transfer of cytochrome c from mitochondria to
      the cytosolic compartment, may be directly involved in the generation of the
      mitochondrial membrane potential at the beginning of the cell death process.

PMID- 9610402
TI  - Chromosomes and expression mechanisms. Web alert.

PMID- 9610403
TI  - The histone tails of the nucleosome.
AB  - Reversible acetylation of core histone tails plays an important role in the
      regulation of eukaryotic transcription, in the formation of repressive chromatin
      complexes, and in the inactivation of whole chromosomes. The high-resolution X
      ray structure of the nucleosome core particle, as well as earlier evidence,
      suggests that the histone tails are largely responsible for the assembly of
      nucleosomes into chromatin fibers and implies that the physiological effects of
      histone acetylation may be achieved by modulation of a dynamic inter-conversion
      between the fiber and a less condensed nucleofilament structure. In addition, the
      tails and adjacent regions serve as recognition sites for chromatin assembly and
      transcription remodeling machinery and the interactions that occur may also be
      responsive to histone acetylation.

PMID- 9610404
TI  - Unfolding the mysteries of heterochromatin.
AB  - The function of heterochromatin has not been well understood. Recent studies,
      however, demonstrate that heterochromatin is essential for proper chromosome
      behavior. The silencing of euchromatic genes by heterochromatin has been
      exploited to understand the molecular nature of heterochromatin. Mutations that
      either suppress or enhance gene silencing exist within chromatin structural
      proteins and modifying enzymes. Interactions between some of these proteins have
      been demonstrated, suggesting a complicated picture of heterogeneous silencing
      complexes that are counteracted by protein-modifying machinery.

PMID- 9610405
TI  - Imprinting mechanisms in mammals.
AB  - Imprinting is a genetic mechanism that determines expression or repression of
      genes according to their parental origin. Some imprinted genes occur in clusters
      in the genome. Recent work using transgenic mice shows that multiple cis-acting
      sequences are needed for correct imprinting. Mutation analysis in a normal
      chromosomal context reveals the importance of imprinting centres for regional
      establishment or maintenance of imprinting in a cluster. Elements that contribute
      to the function of imprinting centres and regional propagation of the imprints
      are CpG-rich differentially methylated regions (that during development retain
      germline imposed methylation or demethylation), direct repeat clusters, and
      unusual RNAs (antisense, non-translated etc.). The interaction of these cis
      elements with transacting factors such as methylase and chromatin factors
      establishes a hierarchical control system with local and regional effects.

PMID- 9610406
TI  - Transcription of chromatin: these are complex times.
AB  - Transcription of chromatin-packaged genes involves highly regulated changes in
      nucleosomal structure that control DNA accessibility. Two systems that facilitate
      these changes are ATP-dependent chromatin remodeling complexes and enzymatic
      complexes which control histone acetylation and deacetylation. Recent studies
      provide insight on the role of these remodeling machines and specific
      transcription factors in the expression of viral, inducible, and tissue
      restricted genes.

PMID- 9610407
TI  - Covalent modifications of histones: expression from chromatin templates.
AB  - Recent advances highlight the involvement of histone acetyltransferases in
      transcriptional activation and histone deacetylases in transcriptional
      repression. Transcription factors loaded onto regulatory DNA elements may recruit
      either coactivators with histone acetyltransferase activity or corepressors
      associated with histone deacetylases. The recruited enzymes may either acetylate
      or deacetylate proximal nucleosomal histones or nonhistone chromosomal proteins.

PMID- 9610408
TI  - Dosage compensation in flies and worms: the ups and downs of X-chromosome
      regulation.
AB  - Dosage compensation ensures that individuals with a single X chromosome have the
      same amount of most X-linked gene products as those with two. In Drosophila, this
      equalization is achieved by a two-fold enhancement of the level of transcription
      of the X in males (XY) relative to each X chromosome in females (XX). In
      Caenorhabditis, equalization of X-linked gene products between hermaphrodites
      (XX) and males (XO) is achieved by decreasing the activity of genes in the
      former. These two different solutions to the common problem of unequal dosage of
      X-linked genes in different sexes provide invaluable paradigms for the study of
      gene regulation at the level of chromatin remodeling.

PMID- 9610409
TI  - DNA damage checkpoints update: getting molecular.
AB  - Eukaryotic checkpoint controls impose delays in the cell cycle in response to DNA
      damage or defects in DNA replication. Genetic and physiological studies in
      budding yeast have identified key genes and defined genetic pathways involved in
      checkpoint-mediated responses. Recent studies now lead to biochemical models that
      explain at least in part the arrest in G1 and delays during DNA replication after
      damage. Though progress in checkpoint controls has indeed been rapid, several
      observations identify puzzling aspects of checkpoint controls with few plausible
      explanations.

PMID- 9610410
TI  - Replication origins in yeast versus metazoa: separation of the haves and the have
      nots.
AB  - The recent flood of information concerning Saccharomyces cerevisiae replication
      origins and the proteins that interact with them contrasts alarmingly to the
      trickle of progress in our understanding of metazoan origins. In mammalian cells,
      origins are complex and heterogeneous, and appear to be selected by features of
      nuclear architecture that are re-established after each mitosis. Studies in
      Xenopus egg extracts have shown that once per cell cycle replication does not
      require specific origin sequences, despite the identification of functional
      homologues to yeast origin-binding proteins. These observations suggest that
      initiation of DNA replication in higher eukaryotes is focused to specific genomic
      regions by features of chromosome structure.

PMID- 9610411
TI  - Recombination at work for meiosis.
AB  - In sexually reproducing organisms, homologous recombination increases genetic
      diversity in gametes and ensures proper chromosome segregation. Recent
      publications have provided details of the molecular intermediates and proteins
      involved, the control of the distribution of recombination events at the
      chromosomal level, and the surveillance mechanisms that coordinate recombination
      with the meiotic cell cycle.

PMID- 9610412
TI  - Centromeres: proteins, protein complexes, and repeated domains at centromeres of
      simple eukaryotes.
AB  - Similarities exist among components of simple and complex centromeres that may
      not have been expected on the basis of wide variation in size and sequence
      organization of centromeric DNAs among eukaryotes. Support is growing in systems
      from fungi to Drosophila for a model of centromere assembly and activation that
      is dependent on a particular underlying chromatin structure but not necessarily
      on a specific DNA sequence.

PMID- 9610413
TI  - Centromeres: the missing link in the development of human artificial chromosomes.
AB  - Successful construction of artificial chromosomes is an important step for
      studies to elucidate the DNA elements necessary for chromosome structure and
      function. A roadblock to developing a tractable system in multicellular
      organisms, including humans, is the poorly understood nature of centromeres.
      Progress, has been made in defining the satellite DNA that appears to contribute
      to the centromere in both humans and Drosophila and large arrays of alpha
      satellite DNA have been used to construct first-generation human artificial
      chromosomes. Non-satellite DNA sequences are also capable of forming 'neo
      centromeres' under some circumstances, however, raising questions about the
      sequence-dependence of centromere and kinetochore assembly. Taken together with
      new information on the nature of protein components of the kinetochore, these
      data support a model in which functional kinetochores are assembled on
      centromeric chromatin, the competence of which is established epigenetically. The
      development of human artificial chromosome systems should facilitate
      investigation of the DNA and chromatin requirements for active centromere
      assembly.

PMID- 9610414
TI  - Telomerase and chromosome end maintenance.
AB  - The past year has seen significant advances in our understanding of telomerase
      and other factors involved in chromosome end maintenance. The protein subunit of
      telomerase that provides the active site for telomeric DNA synthesis was
      identified in ciliates, yeast and mammals. It is structurally related to reverse
      transcriptase and thus represents the first member of this protein family with an
      essential cellular function. Telomere DNA-binding proteins that may mediate the
      interaction of telomerase with telomeres have been identified and further
      characterized in diverse eukaryotes. A further elucidation of telomeric DNA
      structure has influenced our view of how telomeres replicate.

PMID- 9610415
TI  - Mechanisms of silencing in Saccharomyces cerevisiae.
AB  - In the yeast Saccharomyces cerevisiae, heterochromatin-like regions are formed at
      the silent mating type loci and at telomeres. The past year of investigations has
      led to a clearer understanding of the nature of nucleation and spreading of
      heterochromatin, as well as uncovering a fascinating link between silencing, the
      nucleolus and aging.

PMID- 9610416
TI  - Chromosomal imprinting in plants.
AB  - Chromosomal imprints in the broadest sense can arise in somatic as well as
      germline cells. They can be imposed through the modification of chromosomal
      proteins or by the modification of chromosomal DNA, and they typically effect the
      expression of nearby genes. Modification enzymes--such as histone deacetylases
      and cytosine methyltransferases, as well as chromatin components--are known to
      play this role in animals and many of these same enzymes and components have been
      found in plants. Transposable elements are subject to chromosomal imprinting and
      may play a fundamental role in this process in plant and other eukaryotic
      genomes.

PMID- 9610417
TI  - Fragile-X syndrome and myotonic dystrophy: parallels and paradoxes.
AB  - Fragile-X syndrome and myotonic dystrophy are caused by triplet repeat expansions
      embedded in CpG islands in the transcribed non-coding regions of the FMR1 and the
      DMPK genes, respectively. Although initial reports emphasized differences in the
      mechanisms by which the expanded triplet repeats caused these diseases, results
      published in the past year highlight remarkable parallels in the likely molecular
      etiologies. At both loci, expansion is associated with altered chromatin,
      aberrant methylation, and suppressed expression of the adjacent FMR1 and DMAHP
      genes, implicating epigenetic mediation of these genetic diseases.

PMID- 9610418
TI  - Chromosome dynamics: the SMC protein family.
AB  - Recent evidence suggests that members of the structural maintenance of
      chromosomes (SMC) protein family are involved in a much broader spectrum of
      chromosome and DNA metabolic reactions than was originally thought. Other than
      their role in chromosome condensation, SMC proteins are essential for sister
      chromatid cohesion and gene dosage compensation, and are involved in DNA
      recombination. This diversity of function is achieved both through the formation
      of different heterodimers and through their participation in higher-order protein
      complexes adapted to achieve specific ends.

PMID- 9610419
TI  - One additional mutation at exon A amplifies thermolability of androgen receptor
      in a case with complete androgen insensitivity syndrome.
AB  - We have previously demonstrated a substitutional mutation (glycine to alanine at
      position 820) of the androgen receptor (AR) gene in a patient with complete
      androgen insensitivity syndrome (CAIS). We first examined whether the mutation
      could lead to a disorder in AR binding activity in in vitro expression
      experiments. In a luciferase assay, the effect of the mutant AR on a target's
      gene was definitely impaired. However, the mutant AR had less thermal instability
      compared to that of the patient's fibroblast cell lines established in a whole
      cell binding assay. In order to analyze the cause of the thermal instability, a
      further analysis of exon A in the AR gene was performed because the previous
      study had been performed only between exon B and H encoding the DNA-binding
      domain and the hormone-binding domain. The second mutation (leucine to proline at
      position 257) was newly identified. In in vitro expression experiments, the AR
      with both mutations showed marked thermal instability, whereas the AR with a
      mutation in exon A had no effect on thermal stability. The results show that the
      N-terminal domain might also play an important role in amplifying or modifying
      the AR binding activity.

PMID- 9610420
TI  - Pregnancy in patients with Turner's syndrome: six new cases and review of
      literature.
AB  - Pregnancy in women with Turner's syndrome (TS) is an exceptional event, but is
      possible in 2% of cases. It can occur in patients with structural anomalies of
      the X chromosomes in which the Xq13-q26 region, containing the genes that are
      thought to control ovarian function, is spared; or in patients with a mosaic
      karyotype containing an 46,XX cell line, which preserves ovarian function. In our
      Centre we observed six cases of women with Turner's syndrome conceiving. Out of
      13 pregnancies, there were six abortions and eight live-births; among the latter,
      four babies exhibited malformations. Reviewing the literature shows that out of
      160 pregnancies which occurred in 74 women with TS, 29% ended in spontaneous
      abortion, 7% led to the perinatal death of the fetus, 20% gave birth to malformed
      babies (TS, Down's syndrome, etc.) and only in 38% of cases were healthy children
      born. This study suggests that the rare TS patients who are able to procreate
      should undergo prenatal diagnosis techniques. In sterile TS patients the use of
      artificial fertilization techniques is a possible solution.

PMID- 9610421
TI  - The incidence of 21 alpha-hydroxylase deficiency in Greek hyperandrogenic women:
      screening and diagnosis.
AB  - The purpose of this prospective study was to determine the incidence of any form
      of 21 alpha-hydroxylase deficiency among Greek women with hyperandrogenic
      symptoms, and to test the predictive value of basal serum 17-hydroxyprogesterone
      (17-OHP) in the early follicular phase as a screening index for patient
      preselection to adrenocorticotropic hormone (ACTH) testing. Eighty-eight
      unselected women with hyperandrogenic symptoms were examined in the Gynecological
      Endocrinology Unit of the Second Department of Obstetrics and Gynecology of
      Athens University. Using the ACTH-stimulated 17-OHP values at 60 minutes (17
      OHP60) the study population was divided into four groups (A, B, C and D).
      Clinical and basal hormonal parameters as well as serum 17-OHP60 values and human
      leukocyte antigens were studied. Both clinical and basal hormonal parameters
      could be used to distinguish only patients with severe 21 alpha-hydroxylase
      deficiency (group A). In contrast, patients with moderate non-classical
      congenital adrenal hyperplasia (NC-CAH; group B), heterozygotes for NC-CAH (group
      C), and unaffected females (group D) can be diagnosed and classified only by
      serum 17-OHP60 values. In conclusion, the incidence of NC-CAH in Greek females
      with hyperandrogenic symptoms is 3.4%. The positive predictive value of basal 17
      OHP is only 13% for this disease. Only 17-OHP60 helps to diagnose and classify
      moderate and mild forms of NC-CAH. Thus, it seems that ACTH testing is imperative
      in every subject suspected of this enzymatic disorder.

PMID- 9610422
TI  - Combined somatostatin analog and follicle-stimulating hormone for women with
      polycystic ovary syndrome resistant to conventional treatment.
AB  - This study was undertaken to determine whether somatostatin analog in combination
      with human urinary follicle-stimulating hormone (FSH) improves ovulatory
      performance in patients with polycystic ovarian syndrome (PCOS) who failed to
      respond to FSH alone. A comparative prospective study was performed in six
      insulin-resistant, hyperandrogenic, PCOS women treated with somatostatin analog
      combined with FSH for one cycle. Individual ovulatory performance was compared to
      the cumulative ovulatory response of three previous cycles. Somatostatin analog
      was administered subcutaneously by means of an infusion pump, providing a total
      daily dose of 200 micrograms starting from days 1-3 of the cycle. Induction of
      ovulation with FSH was initiated on day 5 of the stimulated cycle. Vaginal
      ultrasonography for follicular surveillance was performed before the pump setting
      and during the treatment cycle. A significant decrease in insulin, insulin-like
      growth factor (IGF-I), growth hormone (GH) and luteinizing hormone (LH) was
      observed during the combined somatostatin analog-FSH treatment cycles. The
      follicular growth patterns and the incidence of ovarian hyperstimulation syndrome
      (OHSS) was not affected. These observations suggest that adjuvant therapy with
      somatostatin analog may have a beneficial effect on the hormonal response of PCOS
      patients to gonadotropin induction of ovulation.

PMID- 9610423
TI  - Gonadotropin ovulation induction and pregnancies in women with Kallmann's
      syndrome.
AB  - Only 17 cases of pregnancy in women with Kallmann's syndrome have been reported
      in the literature, eight as case reports. In our clinic, we diagnosed seven women
      with complete Kallmann's syndrome in a 16-year period. In five cases (unprimed
      patients) the diagnosis was established for the first time, while in the other
      two cases diagnosis had been established earlier. The five unprimed patients
      received hormone therapy (HRT) immediately after diagnosis. The other two
      patients had already been on HRT. Four patients wanted to bear children.
      Follicular evolution and maturation was induced with daily human menopausal
      gonadotropin (hMG) administration. The results were monitored through plasma
      estradiol (E2) determinations and ultrasonography. Ovulation was induced with hCG
      administration. Five pregnancies were achieved in three patients, resulting in
      four healthy neonates. Two women achieved a second pregnancy. Nausea and vomiting
      did not occur in any of our five pregnancies. We found no significant differences
      between the total hMG dose needed for ovulation induction, the number of
      stimulation days, estradiol plasma concentrations and the number of follicles
      with diameter > or = 17 mm, in either conceptional or non-conceptional cycles. In
      fact, the total hMG dose administered was lower and the days of stimulation were
      significantly fewer in women on their second pregnancy. There was no difference
      in plasma estradiol concentrations and the number of follicles with diameter > or
      = 17 mm. In conclusion, ovulation induction and pregnancy in women with complete
      Kallmann's syndrome is not such a difficult procedure as was believed in the
      past. A previous pregnancy seemed to augment ovarian sensitivity to
      gonadotropins.

PMID- 9610424
TI  - Combined oral estradiol valerate-norethisterone treatment over three years in
      postmenopausal women. 1. Clinical aspects and endometrial histology.
AB  - The aim of this study was to determine the medium-term safety and efficacy of
      once-daily, oral estradiol valerate 2 mg with norethisterone 0.7 mg on menopausal
      symptoms, bleeding incidence, endometrial pathology, adverse events and other
      clinical parameters. A three-year, single-center, open study was performed. Women
      with menopausal symptoms and > or = 6 months since the last spontaneous menstrual
      period were recruited. Patients were assessed using questionnaires and daily
      records of bleeding incidence and severity. Adverse events were recorded at each
      visit and endometrial histopathology was determined at baseline and annually.
      There were 206 patients at entry and 133 completers at the end of year 3.
      Menopausal symptoms showed significant improvements within 4 months (p < 0.0001
      compared with baseline). By the end of month 4, 79.9% of patients had stopped
      bleeding. The mean number of days bleeding per month declined from 2.8 (month 1)
      to 1.1 (month 12). Significantly less bleeding was observed in patients who were
      > or = 2 years postmenopausal. No abnormalities in endometrial histology were
      found. Bleeding and breast tenderness were the commonest adverse events. Twenty
      four patients experienced serious adverse events although no definite
      relationship to drug therapy was considered likely. We therefore conclude that
      the oral combination of estradiol valerate 2 mg and norethisterone 0.7 mg given
      daily and continuously leads to amenorrhea and symptom alleviation in the
      majority of patients and is well tolerated.

PMID- 9610425
TI  - Hormonal breast augmentation: prognostic relevance of insulin-like growth factor
      I.
AB  - Many women would like to after their breasts but are deterred by the risks
      involved. Silicone breast implants have been linked to a variety of illnesses,
      the most controversial of which are connective-tissue diseases. These
      circumstances urged us to perform this pilot study using a non-invasive method
      that involved the application of 17 beta-estradiol as it is known that estradiol
      enhances expression of insulin-like growth factor-I (IGF-I) which can promote
      growth in breast tissue. Forty-five women were included in the study. Their
      breast volume, IGF-I, prolactin (PRL) and estradiol levels were measured before
      treatment and between each application of 80 mg estradiol polyphosphate. The
      women's satisfaction with the results obtained was also subsequently evaluated.
      In 21 women (46.7%), breast size increased from 824.3 +/- 13.7 mm to 898.5 +/-
      12.5 mm after 6 months. In these women a significant increase in IGF-I values was
      noted after 4 weeks of treatment. The increase in IGF-I values was not
      statistically significant in the remaining women. In addition, treatment was not
      successful in these women. IGF-I concentration seems to be of prognostic value as
      far as the response of breast tissue to estrogen stimulation is concerned. If IGF
      I levels do not increase within 1 month, treatment should be discontinued. If IGF
      I values do increase, this indicates that treatment is likely to be successful
      and can therefore be continued.

PMID- 9610426
TI  - Interrelationships between oxytocin and eicosanoids in human fetal membranes at
      term gestation: which role for leukotriene B4?
AB  - The existence of a functional paracrine loop between oxytocin and prostaglandin
      F2-alpha in human placental cells has been demonstrated. The present study was
      undertaken to investigate further the possible interrelationships between
      oxytocin and eicosanoids in human intrauterine tissues at term gestation.
      Therefore, we evaluated the effect of leukotriene B4 (LTB4) on oxytocin (OT)
      production by explants of fetal membranes and amnion and the effect of oxytocin
      on the production of LTB4 and prostaglandin E2 (PGE2) by both fetal membranes and
      amnion. In all cases studied (n = 25), short-term cultures of tissue explants
      (fetal membranes or amnion) have been carried out. The production of eicosanoids
      and oxytocin in culture medium was evaluated. Oxytocin measurement was carried
      out by radioimmunoassay following extraction of the substance with Sep Pak C18
      cartridges, PGE2 and LTB4 were measured by radioimmunoassay directly in culture
      medium. Results show that LTB4 has no significant stimulatory effect on oxytocin
      production by fetal membranes or amnion tissue. On the other hand, oxytocin
      stimulates PGE2 release by both fetal membranes and isolated amnion, but has no
      effect on LTB4 production by these tissues. Taken together, these findings
      suggest the following conclusions: (1) a paracrine loop between LTB4 and oxytocin
      is lacking in fetal membranes and amnion at term pregnancy; (2) oxytocin exerts a
      stimulatory effect on PGE2 release by both fetal membranes and amnion; (3) the
      interrelationships between oxytocin and the different eicosanoids in the above
      tissues seem to be highly selective.

PMID- 9610427
TI  - The transition from pubertal development to postmenopause discloses a
      gonadotropin-releasing hormone-independent mechanism regulating follicle
      stimulating hormone release.
AB  - The reproductive function is tightly dependent on gonadotropin secretion and the
      optimal activity of the hypothalamus-pituitary axis. This study discusses
      evidence that supports the possible existence of a GnRH-independent modulator of
      FSH secretion in humans. Such a hypothesis has been consistently reported in
      several experimental animals. To test the hypothesis specific times during the
      physiological development and activity of the hypothalamus-pituitary axis have
      been evaluated under the use of drugs acting directly on hypothalamic GnRH
      secreting neurons, such as GnRH agonists. The possible presence also in humans of
      such an independent FSH stimulator might be important for the understanding of
      anovulation and infertility.

PMID- 9610428
TI  - Beta-adrenoceptor subtypes and their desensitization mechanisms.

PMID- 9610429
TI  - Effect of cyclopiazonic acid on contractions produced by tachykinin NK1 and NK2
      receptor agonists in the circular muscle of guinea-pig colon.
AB  - 1 This study aimed to assess the effect of cyclopiazonic acid (CPA), an inhibitor
      of sarcoplasmic reticulum calcium (Ca) pump, against contractile responses
      produced by selective tachykinin NK1 and NK2 receptor agonists, [Sar9]substance P
      (SP) sulfone and [beta Ala8]neurokinin A (NKA) (4-10), respectively, on the
      circular muscle of guinea-pig colon. All experiments were performed in the
      presence of atropine (1 microM) and indomethacin (10 microM). 2 In organ bath
      experiments, a submaximally equieffective concentration of the two agonists (10
      nM) was selected: [Sar9]SP sulfone (10 nM) produced a biphasic contraction, the
      two amplitudes averaging 75 +/- 2 and 43 +/- 3% of the maximal response to KCl
      (80 mM) at 1 and 15 min from application of the agonist, respectively. CPA (3
      microM for 60 min) slightly reduced the phasic response to [Sar9]SP sulfone (16
      +/- 4% inhibition) and markedly suppressed the tonic component (89 +/- 3%
      inhibition). 3 The contraction produced by [beta Ala8]NKA (4-10) (10 nM) was more
      sustained than that induced by the NK1 receptor agonist: it averaged 69 +/- 5 and
      73 +/- 4% of the response to KCl at 1 and 15 min from application of the agonist,
      respectively. CPA slightly and evenly depressed the response to [beta Ala8]NKA (4
      10) (18 +/- 7 and 21 +/- 5% inhibition at 1 and 15 min). 4 In the presence of
      tachykinin NK1 and NK2 receptor antagonists (SR 140333 and MEN 10627,
      respectively, 1 microM each) and of L-nitroarginine (100 microM), KCl (40 mM)
      produced a distinct phasic and tonic contraction which was suppressed by 1 mM
      nifedipine. CPA (3 microM) did not affect the phasic contraction to KCl but
      abolished the tonic component of the response. 5 In the presence of 1 microM
      nifedipine, the response to [beta Ala8]NKA (4-10) was slightly depressed (32 +/-
      6% inhibition) in its early component only, while the response to [Sar9]SP
      sulfone was abolished. CPA produced a slight inhibition (15 +/- 9 and 33 +/- 10%
      at 1 and 15 min, respectively) of the nifedipine-resistant response to [beta
      Ala8]NKA (4-10), an effect similar to that observed in the absence of nifedipine.
      Therefore, a large part of the response to [beta Ala8]NKA (4-10) persisted in the
      presence of both CPA and nifedipine. 6 In the sucrose gap, a prolonged
      superfusion with [Sar9]SP sulfone (0.1 microM for 5 min) produced sustained
      depolarization with superimposed spikes and contraction. CPA (3 microM) produced
      transient depolarization and contraction. In the presence of CPA, the initial
      responses (depolarization, spikes and contraction) to [Sar9]SP sulfone were
      unaffected but the sustained component of contraction was absent; the latter
      effect was accompanied by a suppression of spikes while the sustained
      depolarization was present. 7 We conclude that, during sustained depolarization
      produced by the NK1 receptor agonist, blockade of the sarcoplasmic reticulum Ca
      pump by CPA produces a faster Ca-dependent inactivation of Ca channels, thereby
      eliminating spikes and abolishing the tonic component of contraction. Ca
      mobilization/reuptake from a CPA-sensitive store seems to be of minor importance
      for regulating the NK2 receptor-mediated contractile responses.

PMID- 9610430
TI  - Effects of noise stress on EFS-mediated cholinergic and inhibitory NANC responses
      in tracheae from normal and sensitized guinea-pigs.
AB  - 1 The aim of the present research was to study the cholinergic and inhibitory non
      adrenergic-non-cholinergic (NANC) responses obtained with electrical field
      stimulation (EFS) of tracheal tissues from sham- and noise-exposed guinea-pigs. A
      comparison was also made between normal and ovalbumin (OA)-sensitized animals. 2
      In proximal tracheae pretreated with indomethacin (3 microM), propranolol (1
      microM), alpha-chymotrypsin (2 U ml-1) and L-NAME (0.1 mM), frequency-dependent
      responses to EFS (0.1 ms width; 20 V, 0.1-100 Hz, 15 s train duration) were
      obtained, both contractile and relaxing in nature. The contractile responses were
      abolished by atropine (1 microM), and did not vary significantly between sham-
      and noise-exposed guinea-pigs, or between normal and sensitized animals. The NANC
      relaxing responses, present in spite of the pre-treatment of the tissues with L
      NAME and alpha-chymotrypsin, and almost completely abolished by tetrodotoxin
      (TTX) treatment (10 microM), appeared to be enhanced in noise-exposed guinea
      pigs, with respect to sham-exposed animals, but only when the animals were not OA
      sensitized. 3 In distal tracheae contracted with histamine (10 microM), the study
      of the whole inhibitory NANC response (pre-treatment with propranolol, but not
      with alpha-chymotrypsin and L-NAME), which was mainly TTX-sensitive, revealed a
      statistically non-significant difference between sham- and noise-exposed guinea
      pigs, both normal and OA-sensitized. When distal tracheae were preincubated with
      alpha-chymotrypsin (2 U ml-1) and L-NAME (0.1 mM), in addition to propranolol, a
      significant residual inhibitory NANC response to EFS was observed. Surprisingly,
      in this case, similarly to the evidence obtained in proximal tracheae, a
      significantly enhanced response was revealed in noise-exposed guinea-pigs with
      respect to sham-exposed animals. 4 The noise-induced enhancement of the relaxant
      response disappeared when the tissues were pretreated with the A2 purinergic
      antagonist 3,7-dimethyl-1-propargylxanthine (DMPX, 1 microM), while it persisted
      in the presence of the A1 antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX,
      10 nM). 5 The above data indicate that, while not modifying the cholinergic and
      the whole inhibitory NANC response to EFS, noise stress selectively influences an
      inhibitory component of the NANC system in guinea-pig trachea with a mechanism
      probably involving an enhanced neurally mediated release of adenosine, which
      relaxes the smooth muscle via A2 receptors. This effect appears to be lacking or
      masked in sensitized guinea-pigs.

PMID- 9610431
TI  - Muscarinic modulation of endogenous noradrenaline release from adrenergic
      terminals in the guinea-pig colon.
AB  - 1 The present study examined the role of muscarinic receptors in the modulation
      of noradrenaline (NA) release in the guinea-pig isolated distal colon. The
      spontaneous endogenous NA overflow assayed by HPLC-ED was taken as an index of NA
      release from enteric noradrenergic nerve terminals. 2 Physostigmine (10 microM)
      significantly enhanced spontaneous endogenous NA overflow. Hyoscine (muscarinic
      antagonist), (R)-(-)-trihexyphenidyl and telenzepine (M1-selective antagonists),
      and 11[[2-[(diethylamino)methyl]-1-piperydil]acetyl]-5,11 -dihydro-6H-pyrido[2,3
      b][1,4]benzodiazepine-6-one (AF-DX 116, M2-selective antagonist) inhibited NA
      overflow in a concentration dependent manner, with the following EC50 values:
      131.74 (18.19-953.96), 101.62 (58.83-175.60), 150 (60-330), 30 (5-170) nM,
      respectively. 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, M1- and M3
      selective antagonist) had no significant effect up to 100 microM. 3 The
      muscarinic agonist oxotremorine inhibited NA overflow in a concentration
      dependent manner, with an EC50 value of 0.67 (0.30-1.51) microM. The response to
      oxotremorine was inhibited by muscarinic antagonists with the following order of
      potency: hyoscine = (R)-(-)-trihexyphenidyl = telenzepine > 4-DAMP >> AF-DX 116.
      4 In the presence of 3 microM tetrodotoxin (TTX), the effect of oxotremorine and
      4-DAMP was unchanged, while hyoscine, (R)-(-)-trihexyphenidyl, telenzepine and AF
      DX 116, instead of inhibiting, significantly enhanced NA overflow. 5 The present
      results indicate that, in the guinea-pig colon, endogenous acetylcholine sustains
      spontaneous NA release by activating muscarinic receptors possibly located on
      interneurones. In addition, inhibitory muscarinic receptors may exist on
      adrenergic terminals.

PMID- 9610432
TI  - Postanesthetic hypotropia.

PMID- 9610433
TI  - Hyposecretion of aqueous: another mechanism for reduced intraocular pressure
      after phacoemulsification.

PMID- 9610435
TI  - Treatment of fibrinous effusion.

PMID- 9610434
TI  - Corticosteroids and antibiotics in combination.

PMID- 9610436
TI  - Consultation section. Refractive surgical problem.

PMID- 9610437
TI  - Closed-chamber capsulorhexis for cataract extraction combined with penetrating
      keratoplasty.
AB  - We describe a modified closed-chamber capsulorhexis technique that facilitates
      cataract extraction and intraocular lens insertion combined with penetrating
      keratoplasty. This technique eliminates most of the risks associated with can
      opener capsulotomies, offers the benefits of capsulorhexis, and enhances the
      safety of the triple procedure.

PMID- 9610438
TI  - Phacoemulsification and combined management of intraocular silicone oil.
AB  - We report two techniques in which cataract extraction is carried out by
      phacoemulsification through a corneal incision. If silicone oil is to be removed,
      a posterior continuous curvilinear capsulorhexis is performed, allowing
      aspiration of oil through the capsulorhexis followed by lens implantation into
      the remaining capsular bag. If silicone oil is to be left in situ, the remaining
      capsule is removed, converting the cataract extraction to an intracapsular-type
      procedure that retains the advantages of small incision surgery. These techniques
      offer good improvement in vision and retinal view with more rapid rehabilitation
      than conventional large incision surgery. The 20% retinal redetachment is
      comparable to that of other studies and we have not encountered any other
      significant complications with these techniques.

PMID- 9610439
TI  - Three-phase phacoemulsification.
AB  - In phase 1 of three-phase phacoemulsification, an endocapsular nuclear
      emulsification technique, two intersecting grooves divide the nucleus into four
      quadrants. The grooves are short and involve most of the thickness of the
      nucleus. In phase 2, the standard irrigation/aspiration flow is reversed by a
      valve. Fluid enters the eye via the ultrasound tip, and aspirated tissue exits
      through the silicone sleeve. The critical juxtacapsular parts of the nucleus are
      removed with minimal risk of aspirating the capsule, and the four quadrants are
      separated completely. In phase 3, the free quadrants are emulsified in the center
      of the capsular bag. This technique helps prevent capsule rupture and might also
      be less traumatic to the corneal endothelium than traditional two-phase phaco.

PMID- 9610440
TI  - New instrument for revision lamellar refractive surgery.
AB  - A new instrument that aids in retreating or revising lamellar refractive surgery
      is described. The edge delineator and lifter can both delineate and lift the edge
      of a previously made corneal flap.

PMID- 9610441
TI  - Staar Collamer posterior chamber phakic intraocular lens to correct myopia and
      hyperopia.
AB  - PURPOSE: To evaluate the efficacy, safety, stability, and predictability of
      implanting a collagen polymer (Staar Collamer), posterior chamber phakic
      intraocular lens (IOL) to correct myopia and hyperopia. SETTING: Centre for
      Advanced Refractive Eye Surgery at the BMI Alexandra Hospital, Cheadle,
      Manchester, United Kingdom. METHODS: A Staar Collamer posterior chamber phakic
      IOL was implanted in 25 eyes of 14 patients with a mean age of 37.9 years (range
      20 to 50 years). Seven patients were men and seven, women. Sixteen were myopic
      and 9, hyperopic. Before treatment, each patient had a thorough evaluation
      including refractive, general, ocular, and social and personal histories. The
      examination included visual acuity, refraction, tonometry, topography, biometry,
      biomicroscopy, pupil size in dim illumination, and posterior segment evaluation
      by a vitreoretinal specialist. Patients were informed about the surgical process
      and expected outcome, their own expectations were discussed, and their consent to
      surgery was obtained. Surgical implantation was performed through a less than 3.0
      mm clear corneal sutureless incision using brief general anesthesia on a day-case
      surgical basis. RESULTS: At 3 months postoperatively, all eyes had a significant
      increase in uncorrected visual acuity, allowing all but two patients (three eyes)
      to manage most activities without spectacles. Adjustment by incisional corneal
      surgery was planned for undercorrected myopic eyes (n = 3). Pupil block glaucoma
      and pigment deposits occurred in one patient each. CONCLUSION: In this short-term
      study, the posterior chamber phakic IOL was predictable, safe, and efficacious in
      the correction of myopic and hyperopic refractive errors, with good refractive
      stability. Long-term follow-up is required to validate that the absence of
      significant complications in most patients is a lasting phenomenon.

PMID- 9610442
TI  - Implantable contact lens for moderate to high myopia: phase 1 FDA clinical study
      with 6 month follow-up.
AB  - PURPOSE: To assess the short-term safety and efficacy of the implantable contact
      lens (ICL) to treat moderate to high myopia. SETTING: Phase 1 U.S. Food and Drug
      Administration clinical study of the ICL conducted at four sites in the United
      States. METHODS: Ten patients with myopia of 7.00 diopters (D) or greater had
      implantation of a Staar Surgical ICL and were examined preoperatively (baseline)
      and 1 day, 1 week, and 1, 3, and 6 months postoperatively. Mean preoperative
      myopia was 7.75 D (range 7.25 to 9.37 D). RESULTS: Six months postoperatively, 5
      of 10 eyes (50%) had an uncorrected visual acuity (UCVA) of 20/20 or better, and
      all eyes had a UCVA of 20/30 or better. All eyes had a best spectacle-corrected
      visual acuity (BSCVA) of 20/20 or better and 6 eyes (60%), of 20/15 or better.
      Six eyes (60%) had an improvement of one or more lines of BSCVA. Mean
      postoperative spherical equivalent was -0.025 D +/- 0.47 (SD). Eight eyes (80%)
      were within +/- 0.250 D of emmetropia, and all were within +/- 1.125 D. No
      intraoperative or postoperative complications or adverse reactions were observed.
      CONCLUSIONS: The results support the short-term safety, efficacy, and
      predictability of ICL implantation to treat moderate to high myopia.

PMID- 9610443
TI  - Minoxidil-induced alteration of corneal topography after radial keratotomy.
AB  - PURPOSE: To determine the antiproliferative effect of minoxidil on human corneal
      epithelium (hCE) proliferation in vitro and to assess whether topical minoxidil
      can significantly alter corneal topography after radial keratotomy (RK) by
      inhibiting myofibroblast activity in the keratotomy wound. SETTING: Corneal
      Research Laboratory, University of Chicago, Illinois, USA. METHODS: In the in
      vitro evaluation, proliferating hCE was exposed to minoxidil (0.1 to 2.0 mM) for
      96 hours to determine the minimum inhibitory dose. Human corneal epithelium cell
      proliferation was assessed by the incorporation of bromodeoxyuridine (BRDU) into
      DNA. In the in vivo analysis, eight New Zealand albino rabbits had an eight
      incision bidirectional RK on one eye and were divided into two groups. The
      control eyes (n = 3) received tobramycin and dexamethasone (TobraDex),
      ciprofloxacin hydrochloride (Ciloxan), and balanced salt solution (BSS) drops
      four times a day for 3 weeks, while the treatment eyes (n = 5) received TobraDex,
      Ciloxan, and minoxidil 1.0 mM drops four times daily for 3 weeks. The net change
      in corneal curvature at 3 weeks was analyzed with corneal topography.
      Myofibroblast activity in the keratotomy wound was assessed using alpha smooth
      muscle actin staining techniques. RESULTS: At concentrations of 1.0 mM and above,
      minoxidil caused a statistically significant, dose-dependent reduction in hCE
      cellular proliferation ranging from 29 to 44% (P < .05). Minoxidil (1.0 mM)
      caused a statistically significant central corneal flattening effect of 4.66
      diopters (D) after RK in the treatment eyes compared with 1.11 D in the control
      eyes (P = .05). Histologically, minoxidil-treated keratotomy wounds lacked cells
      with contractile elements consistent with myofibroblast differentiation. Corneal
      epithelial wound healing was similar in both groups. CONCLUSION: At the
      appropriate dose, topical minoxidil may be a useful adjunctive treatment that can
      reduce the number of undercorrections after mini-RK without apparent toxicity to
      the corneal epithelium.

PMID- 9610444
TI  - Complications of photorefractive keratectomy for myopia: two year follow-up of
      3000 cases.
AB  - PURPOSE: To evaluate the results and complications of photorefractive keratectomy
      (PRK) for myopia. SETTING: Alicante Institute of Ophthalmology, University of
      Alicante, Spain. METHODS: This prospective study evaluated the results and
      complications of the first 3000 cases of PRK performed with a VISX Twenty-Twenty
      excimer laser. Myopia ranged from -1.0 to -14.0 diopters (D) and astigmatism,
      from -1.0 to -5.0 D. Follow-up was 2 years. RESULTS: Ten eyes (0.7%) lost two or
      more lines of best corrected visual acuity 1 year after surgery. Retreatment for
      undercorrection or regression was done in 7.41% in the low myopia group and
      38.69% in the high myopia group. Central islands, which could be detected only on
      videokeratoscopy, occurred frequently but influenced the refractive and visual
      outcomes in few cases. Severe haze was present in 17 eyes only after 1 year
      follow-up. There were no cases of progressive hyperopia. Other complications such
      as eccentric ablation producing astigmatism (n = 15), delayed re
      epithelialization, or recurrent corneal erosion were rare. CONCLUSION: There were
      few complications after PRK in 3000 eyes. With proper patient selection, PRK can
      be considered relatively safe compared with other refractive procedures.

PMID- 9610445
TI  - Excimer laser correction of astigmatism with multipass/multizone treatment. The
      Melbourne Excimer Laser Group.
AB  - PURPOSE: To evaluate the accuracy of excimer laser correction of myopic
      astigmatism by multipass/multizone photoastigmatic refractive keratectomy (PARK).
      SETTING: Tertiary referral ophthalmic hospital with an associated private laser
      facility. METHODS: This study comprised a consecutive series of 332 eyes of 289
      patients who were followed for 6 months. All patients were 18 years or older, had
      stable myopic astigmatism (up to a -19.0 diopters [D] spherical equivalent [SE]
      at the spectacle plane), and had a best corrected visual acuity of at least 20/60
      in both eyes. All eyes were treated with a VISX Twenty-Twenty excimer laser. The
      correction was divided between ablation zones using a multipass/multizone
      treatment paradigm based on the amount of myopia and astigmatism. Patients were
      examined 1 week, and 1, 3, and 6 months after surgery. RESULTS: Analysis of the
      mean percentage of spherical correction across the range of myopic preoperative
      SEs treated demonstrated 90% correction for most amounts of myopic astigmatism.
      Eyes with low myopia (mean preoperative SE < or = -5.0 D) treated with < or = 
      1.0 diopter cylinder (DC) of astigmatism achieved a mean percentage of spherical
      correction of 91% versus 93% in eyes with high myopia (> -5.0 D mean preoperative
      SE). Eyes with low myopia treated with > -1.0 DC of astigmatism achieved a mean
      percentage spherical correction of 90% versus 89% in eyes with high myopia. The
      differences between the two groups were not statistically significant. Patients
      with high relative cylinder (> 80% of total sphere treated) achieved comparable
      results. Analysis of the astigmatic component of the treatment, independent of
      the spherical result, showed a trend toward overcorrection in the high myopia
      group with less than -1.0 DC and a mean astigmatic correction of 89 and 98%,
      respectively, in the low and high myopic astigmatism groups. The mean angle of
      error was +2.0 degrees. CONCLUSION: Multipass/multizone PARK for myopic
      astigmatism demonstrated a high degree of predictability and stability with
      desirable results for low and high levels of astigmatism across the range of
      myopic astigmatism treated by surface ablation.

PMID- 9610446
TI  - Treatment of irregular astigmatism.
AB  - PURPOSE: To treat irregular astigmatism by applying separate appropriate
      treatments in each of the two distinct hemidivisions of the cornea. SETTING:
      Cheltenham Eye Centre, Melbourne, Australia. METHODS: Two general surgical
      strategies are presented. The first applies the principles of optimization
      separately to each corneal hemidivision to achieve the maximum reduction in
      astigmatism when measured topographically and refractively. The second is for
      targeting symmetrical orthogonal topographic goals for each semimeridian to
      create the regular state in differing ways. These are performed in one of the
      following ways: without changing refractive astigmatism; by reducing the
      associated ocular residual astigmatism; by shifting the less favorably placed
      topography semimeridian to the other more favorably located one; by shifting both
      topographic semimeridians to more favorably located sites. This is an alternative
      when a potential improvement in the best corrected visual acuity is sought and
      the maximum reduction of astigmatism is not the priority. RESULTS: The calculated
      treatments necessary to achieve various improved astigmatic states, together with
      each of their respective separate refractive astigmatism targets, are presented.
      A single refractive astigmatism value for the entire cornea is also calculated by
      vector summation. CONCLUSION: Consideration of each of the two distinct
      hemidivisions of the eye enables improved treatment of irregular astigmatism,
      potentially resulting in improved visual outcomes.

PMID- 9610447
TI  - Analysis of light energy distribution by multifocal intraocular lenses through an
      experimental optical model.
AB  - PURPOSE: To analyze and compare the light energy distribution generated by
      multifocal intraocular lenses (IOLs). SETTING: Laser Laboratory of the Department
      of Electronics, Electrotechnics and Informatics, University of Trieste, Italy.
      METHODS: An optic system to examine the division of a laser beam in the various
      focal spots of multifocal IOLs was developed. The model consists of a helium-neon
      laser and an optical system: a triangular optical bench with a precision
      collimator, a micropositionable immersion stage supporting the IOL to be
      measured, and a digital image-processing system. Four bifocal and three
      multifocal IOLs were studied. This system is able to expand the distance between
      foci, leading to a sharper separation of the focal spots. The resolution of the
      images makes it possible to analyze the distribution of total light energy among
      the foci. RESULTS: Results showed the variation in light intensity of the focal
      spots of multifocal and bifocal IOLs, as well as their disposition in the
      dioptric range. CONCLUSION: Light distribution among various focal distances
      corresponded to the foci provided by monofocal, bifocal, and multifocal IOLs. The
      percentage of light energy distribution was related to the importance of each
      focus.

PMID- 9610448
TI  - Contrast sensitivity after implantation of diffractive bifocal and monofocal
      intraocular lenses.
AB  - PURPOSE: To compare contrast sensitivity (CS) after implantation of a diffractive
      bifocal intraocular lens (IOL) and a monofocal IOL of similar design. SETTING:
      Seven European centers. METHODS: In this randomized, prospective study, CS was
      tested 5 months after cataract and IOL implantation surgery in 115 patients with
      a diffractive bifocal IOL and 106 patients with a monofocal IOL. It was also
      tested in a subgroup of 38 patients who had bilateral implantation of a
      diffractive bifocal IOL. Contrast sensitivity was tested using the Vision
      Contrast Test System (VCTS). RESULTS: In patients with a best corrected visual
      acuity (BCVA) of 1.0 or better, the CS at all spatial frequencies (1.5 to 18
      cycles/degree), both at distance and near, was slightly lower in the bifocal IOL
      group than in the monofocal group. Mean values were within the normal range. In
      patients with a BCVA of less than 1.0, the CS was lower and the difference
      between the bifocal and monofocal groups was less. In patients with bilateral
      bifocal IOLs, CS was better when tested bilaterally than when testing the better
      eye alone. Pupil size affected the results to a small degree. Contrast
      sensitivity appeared to improve over time after implantation of a diffractive
      bifocal IOL. CONCLUSIONS: In patients with cataract and no other eye pathology,
      the diffractive bifocal IOL with slightly reduce the CS at all spatial
      frequencies. In those with reduced visual acuity after cataract surgery, CS will
      be reduced accordingly. In this situation, the reduction from the diffractive
      bifocal optic would be minor.

PMID- 9610449
TI  - Contrast sensitivity and glare disability with diffractive and refractive
      multifocal intraocular lenses.
AB  - PURPOSE: To compare contrast sensitivity and glare disability provided by
      diffractive and refractive multifocal intraocular lenses (IOLs). SETTING:
      University Eye Clinic Vienna, Austria. METHOD: This study evaluated the contrast
      sensitivity and glare disability in 29 eyes with a diffractive multifocal IOL
      (3M815LE) and 12 with a three-piece, five-zone refractive multifocal IOL (AMO
      Array SSM 26 NB). The Brightness Acuity Tester (Mentor, Inc.) was used with
      stationary sinusoidal gratings at spatial frequencies of 0.5, 1, 3, 6, 11.4, and
      22.8 cycles per degree (cpd) generated on a television monitor (Nicolet CS 2000).
      RESULTS: The contrast sensitivity functions of both multifocal IOL groups were
      within the reference range and were identical at 0.5, 1, and 22.8 cpd spatial
      frequencies. At 3, 6, and 11.4 cpd, the contrast sensitivity function in the
      diffractive IOL group was 6, 9, and 10% lower than in the refractive IOL group,
      and the difference between groups was statistically significant at 6 cpd. When
      glare was present, contrast sensitivity in the diffractive IOL group was
      generally in the lower limit of the reference range and remained below at 3 and 6
      cpd. Contrast sensitivity in the refractive IOL group remained below the
      reference range at 3 cpd. At 0.5 and 1 cpd, there were no differences between the
      groups. At the middle and high spatial frequencies (3, 6, 11.4, 22.8 cpd),
      contrast sensitivity in the diffractive group was 8, 16, 11, and 12% lower than
      in the refractive group. At 6 cpd, the between-group difference was statistically
      significant. CONCLUSION: Diffractive multifocal IOLs provided decreased contrast
      sensitivity and greater glare disability than refractive multifocal IOLs.

PMID- 9610450
TI  - Comparison of pseudoaccommodation and visual quality between a diffractive and
      refractive multifocal intraocular lens.
AB  - PURPOSE: To determine depth of focus and visual quality after implantation of a
      diffractive intraocular lens (IOL) and a refractive IOL. SETTING: University Eye
      Clinic, Vienna, Austria. METHOD: This study comprised 10 eyes of 9 patients with
      a diffractive IOL (3M 825x + 4) and 13 eyes of 9 patients with a refractive lens
      (AMO Array SSM 26NB). Depth of focus was evaluated in a defocused range of -6.0
      to +3.0 diopters (D), and Snellen visual acuity was recorded. RESULTS: Distance
      acuity peaked at 1.0 +/- 0.2 (3M group) and 0.91 +/- 0.13 (AMO group). The near
      acuity peaks were at 0.82 +/- 0.15 and 0.55 +/- 0.14, respectively. Visual acuity
      of 0.5 was possible in a range of defocus of +1.0 to -4.0 D (3M) and +1.0 to -3.5
      D (AMO). CONCLUSION: Pseudoaccommodation and full distance visual acuity were
      realized with both types of multifocal lenses. For intermediate distances, visual
      acuity may be limited to activities that do not require optimal vision. At near
      distances, the 3M lens provided statistically significantly better visual acuity.

PMID- 9610451
TI  - Mini-haptics to improve capsular fixation of plate-haptic silicone intraocular
      lenses.
AB  - PURPOSE: To evaluate the effects of a new mini-haptic design on the strength and
      stability of capsular bag fixation of plate-haptic silicone intraocular lenses
      (IOLs) and determine whether this design encourages the growth of regenerating
      lens material or fibrous tissue around the haptic biomaterial and thus improves
      lens fixation in the capsular bag. SETTING: Center for Research on Ocular
      Therapeutics and Biodevices, Storm Eye Institute, Medical University of South
      Carolina, Department of Ophthalmology, Charleston, South Carolina, USA. METHODS:
      Six rabbits had bilateral continuous curvilinear capsulorhexis,
      phacoemulsification, and plate-haptic silicone IOL implantation. Each rabbit had
      a small-hole plate IOL (Chiron C10UB) implanted in the right eye and a mini
      haptic plate IOL (Chiron C40UB) in the left eye. All rabbits were killed at 2
      months. The force required to extract one haptic from the capsular bag was
      measured with a digital force gauge. Histopathologic analysis was performed on
      all specimens. RESULTS: The mini-haptic style IOLs required significantly more
      extraction force than the small-hole design (P = .011). Histopathologically,
      proliferating lens epithelial cells were observed growing circumferentially
      around the mini-haptics, causing a 360 degree synechia formation. This formation
      did not occur with the conventional small-hole plate IOLs used as the control.
      CONCLUSIONS: Lens epithelial cell proliferation around the mini-haptics
      significantly improved capsular bag fixation of the plate-haptic silicone IOL.
      This should decrease the incidence of clinical decentration and dislocation.

PMID- 9610452
TI  - Dose uniformity of ophthalmic suspensions.
AB  - PURPOSE: To quantify the rate of redispersion of three commercially available
      ophthalmic preparations as well as the drug content of single drops during the
      course of emptying a full container of suspension eyedrops. SETTING: Department
      of Ophthalmology, University of Koln, and Department of Pharmaceutical
      Technology, University of Bonn, Germany. METHODS: In a computer-controlled test
      apparatus used to simulate the shaking and dropping behavior of humans under
      strictly reproducible conditions, we studied the rate of redispersion of three
      ophthalmic suspensions: 50 mg indomethacin, 50 mg prednisolone-21-acetate, and 50
      mg dexamethasone in 5 mL of aqueous fluid. The degree of shaking intensity
      essential for the redispersion of the ophthalmic suspensions was quantified in
      healthy persons and patients by an acceleration sensor. RESULTS: The mean dose
      delivered and the coefficient of variation of prednisolone were satisfactory.
      However, only 25% of the dexamethasone was available for administration; the rest
      remained in the bottle as a cake of sediment. Also, the variability of the drug
      content between drops was unacceptably high. The mean dose of indomethacin was
      adequate, but the between-drop variability was excessive. CONCLUSION: The dose
      uniformity of suspension eyedrops depends on their homogeneity immediately before
      administration. Among the formulation factors studied, particle size appears to
      be the most important. The various redispersion rates of the three drugs
      underline their clinical profile.

PMID- 9610453
TI  - Viscoelastic adherence to corneal endothelium following phacoemulsification.
AB  - PURPOSE: To compare the residual adherence of viscoelastics to the corneal
      endothelium following phacoemulsification in an in vitro rabbit model. SETTING:
      Departments of Ophthalmology and Anatomy, Wayne State University, Detroit,
      Michigan, USA. METHODS: Three groups of 10 rabbit eyes each had a lensectomy via
      phacoemulsification using sodium hyaluronate (Amvisc Plus, Healon GV) or sodium
      chondroitin sulfate-sodium hyaluronate (Viscoat) as the viscoelastic agent. After
      phacoemulsification and cortex removal, a central corneal block was excised,
      cryofixed, and processed for light and electron microscopy. Viscoelastic
      thickness was determined by a calibrated reticule on the light microscope or a
      calibrated measuring program in the electron microscope. The nonparametric
      statistical test, Kruskal-Wallis, was used to compare viscoelastic groups.
      RESULTS: Median phacoemulsification time between viscoelastic agents was not
      significantly different. Median viscoelastic thicknesses were 13.0 microns for
      Amvisc Plus, 0.4 micron for Healon GV, and 375.0 microns for Viscoat. Each was
      significantly different from the others (Kruskal-Wallis, P < .001). CONCLUSIONS:
      Median thickness of Amvisc Plus, Healon GV, and Viscoat remaining adherent to the
      corneal endothelium after phacoemulsification was markedly different. Viscoat
      provided the greatest amount of viscoelastic material adjacent to the corneal
      endothelium.

PMID- 9610454
TI  - Systemic diclofenac sodium to maintain mydriasis during phacoemulsification.
AB  - PURPOSE: To determine whether systemic diclofenac sodium affects the maintenance
      of mydriasis during phacoemulsification and to compare pupil diameter regression
      rates with those in a control group. SETTING: An ophthalmic unit of a National
      Health Service Trust Hospital in the United Kingdom. METHOD: A prospective,
      randomized control study of 100 patients presenting for cataract surgery was
      undertaken. Both groups were administered an identical mydriatic regime
      commencing 1 hour before surgery. In addition, the diclofenac group (n = 48)
      received 50 mg of oral diclofenac sodium 1 hour before surgery. Both the control
      (n = 52) and diclofenac groups had phacoemulsification by one experienced surgeon
      using a standard technique. The surgeon was masked as to which group the patient
      belonged. The irrigating fluid in all cases contained adrenaline. Pupil diameter
      was measured at five stages during surgery and recorded along with the times
      relative to the start of the procedure. RESULTS: Mean pupil diameter in the
      diclofenac group was slightly larger than in the control group, but the
      difference was not significant. Although mean pupil diameter at the start of
      surgery was 0.4 mm greater in the diclofenac group, the slopes of regression in
      pupil diameters were virtually identical between the first three stages of
      surgery, after which a slight reversal occurred in both groups. The slope of
      regression of mydriasis was small in both groups. CONCLUSION: Systemic diclofenac
      sodium 50 mg given orally 1 hour before surgery did not significantly inhibit
      miosis when compared with a control group. Regression rates of pupil mydriasis
      were small in both groups.

PMID- 9610455
TI  - Comparison of energy required for phaco-chop and divide and conquer
      phacoemulsification.
AB  - PURPOSE: To evaluate the safety and usefulness of phaco-chop cataract extraction.
      SETTING: A university-associated, multispecialty ophthalmology practice. METHODS:
      Fifty-three patients in a university-associated ophthalmology practice had
      cataract extraction, 32 by the phaco-chop technique and 21 by four-quadrant
      divide and conquer phacoemulsification. Phacoemulsification energy and
      complication rates were compared. RESULTS: Mean phacoemulsification energy was
      significantly lower in the phaco-chop group (mean 782 J +/- 446 [SD]) than in the
      divide and conquer group (mean 3264 +/- 1218 J)(P < .00001). No complications
      occurred in either group. CONCLUSION: The phaco-chop technique provided safe,
      effective cataract extraction with significantly less energy than that required
      for divide and conquer phacoemulsification.

PMID- 9610456
TI  - Clinical comparison of the Alcon 20,000 Legacy and 10,000 Master
      phacoemulsification units.
AB  - PURPOSE: To determine whether the use of the Alcon 20,000 Legacy
      phacoemulsification unit requires less phacoemulsification time and causes fewer
      intraoperative complications than the Alcon 10,000 Master unit. SETTING: Private
      practices in Kansas City, Missouri, and Marshalltown, Iowa, USA. METHODS: This
      prospective study comprised 400 consecutive cases of phacoemulsification with
      intraocular lens (IOL) implantation performed using the Alcon 20,000 Legacy unit
      by a high-volume phacoemulsification surgeon (n = 200) and a moderate-volume
      surgeon (n = 200). Data included age, phacoemulsification time, and surgical
      complications. The control study was a retrospective review of the same data from
      the previous 200 cases done by each surgeon with the Alcon 10,000 Master unit.
      RESULTS: In the combined series of 400 cases done with the 10,000 Master unit,
      mean age was 72.7 years and mean phacoemulsification (i.e., ultrasound) time,
      1.97 minutes. There were 2 cases (0.50%) of vitreous loss and 3 cases (0.75%) of
      posterior capsule tear without vitreous loss. The total complication rate for
      both surgeons was 1.25% with the 10,000 Master. In the combined series of 400
      cases done with the 20,000 Legacy unit, mean age was 72.5 years and mean
      phacoemulsification time, 1.50 minutes. There were no cases of vitreous loss and
      1 case (0.25%) of posterior capsule tear without vitreous loss. The total
      complication rate for both surgeons was 0.25% with the 20,000 Legacy. The
      difference in complication rates between the two machines was not significant.
      Phacoemulsification time with the 20,000 Legacy unit was significantly less than
      with the 10,000 Master unit for both surgeons (P < or = .001 and .05,
      respectively). CONCLUSION: The Alcon series 20,000 Legacy unit proved to be a
      safe, reliable, and highly effective instrument for modern cataract extraction
      and IOL implantation that required significantly less phacoemulsification time
      than the 10,000 Master unit.

PMID- 9610457
TI  - Factors contributing to retinal detachment after transscleral fixation of
      posterior chamber intraocular lenses.
AB  - PURPOSE: To ascertain the incidence of and factors related to retinal detachment
      (RD) after transscleral suture fixation of posterior chamber intraocular lenses
      (PC IOLs). SETTING: Seoul National University Hospital, Seoul, Korea. METHODS:
      Transscleral fixation of a PC IOL was performed in 122 eyes from January 1990 to
      December 1992. The occurrence of RD was noted and its association with
      preoperative, intraoperative, and postoperative factors evaluated. The type and
      location of retinal tears, extent of detachment, and need for reattachment
      surgery were recorded. Minimum follow-up was 12 months. RESULTS: Six eyes (4.9%)
      developed RD, 5 in the primary implantation group (n = 62; unplanned posterior
      capsule rupture during extracapsular cataract extraction, IOL
      dislocation/subluxation) and 1 in the secondary implantation group (n = 60;
      aphakia after previous cataract surgery); the difference between groups was not
      statistically significant. The factors predisposing to RD were myopia greater
      than -1.0 diopter (P = .03) and postoperative vitreous hemorrhage (P = .001).
      There was no significant difference in the incidence of RD in eyes having
      transscleral fixation in either a primary or secondary procedure and those having
      secondary lens implantation using a different IOL type or surgery with no lens
      implanted. CONCLUSION: The incidence of RD in patients having transscleral PC IOL
      fixation after vitreous loss was not significantly different from that in other
      studies not using transscleral PC IOL fixation with vitreous loss.

PMID- 9610458
TI  - Determining the imaging quality of intraocular lenses.
AB  - PURPOSE: To validate the proposed optical requirements of a draft international
      standard for intraocular lenses (IOLs). SETTING: Eight optical testing
      laboratories in the United States, Germany, Japan, and The Netherlands. METHODS:
      The testing laboratories performed modulation transfer function (MTF) tests on
      various IOLs using a model eye and visual resolution tests in air. Each
      laboratory performed duplicate measurements on a set of 43 lenses that was
      circulated among the testing laboratories. RESULTS: The interlaboratory tests
      showed that the MTF measurements using a model eye had better repeatability and
      reproducibility than the more common industry practice of resolution testing in
      air with parallel light and the United States Air Force three-bar target.
      However, the two methods correlated well. The commonly applied criterion that an
      IOL resolve in air at least 60% of the Rayleigh cutoff spatial frequency
      corresponded to a minimum requirement of 0.43 MTF units at 100 mm-1 in a model
      eye. CONCLUSIONS: Either criterion may be applied in accordance with a proposed
      international standard for IOLs. The model eye method can be applied over a
      broader range of dioptric powers and is relevant for materials that interact with
      aqueous. Both tests appear to have a greater ability to detect unwanted surface
      aberrations than resolution testing of IOLs in a water cell using parallel light,
      a method described in the current American National Standards Institute standard.

PMID- 9610459
TI  - Permanent glaucomatous visual loss after photorefractive keratectomy.
AB  - A 41-year-old man who had photorefractive keratectomy (PRK) for myopia developed
      corneal haze. After intensive treatment with topical corticosteroids, he
      developed elevated intraocular pressure and optic nerve damage. Because of an
      inadequate response to steroid discontinuation and medical treatment, the patient
      required a glaucoma filtering procedure. Corticosteroid-induced glaucoma is a
      possible complication of the treatment often associated with PRK. Careful patient
      screening and disclosure of this risk are imperative.

PMID- 9610460
TI  - Optical iridectomy for corneal opacities in Peter's anomaly.
AB  - Three children were born with partial corneal opacity and anterior segment
      anomalies but no cataract (Peter's anomaly type 1). In each affected eye, the
      corneal scar was off center and encroached on the visual axis. Glaucoma (if
      present) was controlled medically or surgically, after which an optical
      iridectomy was performed in each eye (in lieu of a penetrating keratoplasty).
      After surgery, in all patients the pupil extended beyond the corneal opacity and
      the corneal opacity decreased slightly. All could fixate and follow around the
      opacity. Optical iridectomy should be considered in selected cases of congenital
      corneal opacities.

PMID- 9610461
TI  - Carcinoembryonic antigen in women with isolated pelvic masses. Clinical utility?
AB  - OBJECTIVE: To determine the usefulness of serum carcinoembryonic antigen (CEA)
      determination in predicting the nature of an isolated pelvic mass. STUDY DESIGN:
      Two hundred twenty-six women with an isolated pelvic mass had a serum CEA
      determination preoperatively. The results were correlated with the
      histopathologic findings. RESULTS: CEA was elevated in 19 of the 226 women.
      Twelve of the 183 (7%) women with benign masses, 2 of the 17 (12%) women with
      tumors of low malignant potential and 5 of the 15 (33%) women with a frankly
      invasive epithelial ovarian cancer had elevated CEA. None of the women with a
      malignant germ cell or stromal tumor had elevated CEA (P = .06 for prediction of
      malignancy.) There were no cases of metastatic gastrointestinal malignancies in
      the study group. The sensitivity, specificity, positive predictive value and
      negative predictive value of serum CEA were 16%, 93%, 37% and 83%, respectively.
      The corresponding figures for serum CA-125 were 67%, 71%, 35% and 90%. There was
      no statistically significant correlation between elevated CEA and mucinous
      histology. CONCLUSION: Preoperative serum CEA determination in women with
      isolated pelvic masses is not useful.

PMID- 9610462
TI  - Inducing labor with a sustained-release PGE2 vaginal insert. Experience at a
      community hospital.
AB  - OBJECTIVE: To determine the safety of initiating labor using a sustained-release
      prostaglandin E2 (PGE2) vaginal insert at a nonuniversity-based community
      hospital. STUDY DESIGN: Data were compiled from a chart review of all cases in
      which the insert (Cervidil) was used during a 16-month period. Continuous uterine
      activity and fetal heart rate (FHR) tracings were evaluated for 12 hours after
      dosing. The onset of regular uterine contractions or of active labor and the
      reason for any premature removal of the insert were sought. RESULTS: Regular
      contractions ensued in 62 (35.8%) of 173 pregnancies. Primary reasons for removal
      of the insert in 59 (34.1%) cases were active labor (38), ruptured membranes
      (11), uterine hyperstimulation (7) and a nonreassuring FHR tracing. The average
      time from insertion until premature removal was 5.7 +/- 1.3 (SD) hours (95%
      confidence interval, 3.3-8.2). The insert fell out in nine (5.2%) cases. Cesarean
      delivery for failed labor induction was necessary in five (2.9%) cases. All
      immediate neonatal outcomes were reassuring. Following inservice training, nurses
      were capable of inserting and removing the insert. CONCLUSION: This PGE2 vaginal
      insert, administered and removed by attending nurses, is associated with very low
      rates of uterine hyperstimulation and failed induction. Premature removal of the
      insert occurred in 34.1% of cases.

PMID- 9610463
TI  - Ovarian estradiol production in vivo. Inhibitory effect of leuprolide acetate.
AB  - OBJECTIVE: To determine the impact of reducing the dose of gonadotropin-releasing
      hormone agonist (GnRH-a) for controlled ovarian stimulation in in vitro
      fertilization (IVF) on subsequent response to stimulation and cycle outcome.
      STUDY DESIGN: An IVF database was searched to identify patients who underwent at
      least two cycles of ovarian stimulation at a university-based medical center, and
      a retrospective chart review was performed. Fifty-one patients whose IVF
      stimulation protocols during the two cycles were identical except for the
      leuprolide dosage utilized for luteal pituitary suppression were included in the
      study. Two leuprolide dosages were utilized for suppression: a low dose, 0.5 mg
      daily, and a high dose, 1 mg daily. The leuprolide dose was uniformly halved upon
      initiation of gonadotropin stimulation; the gonadotropin dose and preparation
      were identical in the two protocols. Day 3 follicle-stimulating hormone levels,
      duration of stimulation, amount of gonadotropins required, midcycle and peak
      estradiol levels, oocyte yield and implantation rates were compared. RESULTS:
      Lowering the dose of GnRH-a while maintaining the same stimulation protocol
      resulted in a faster estradiol rise and higher mean peak estradiol level. The
      higher estradiol levels were obtained with a lower total gonadotropin dose. The
      oocyte yield was not affected by the stimulation protocol utilized. CONCLUSION:
      Lowering the dosage of leuprolide allows higher estradiol levels in those
      patients. This suggests an inhibitory in vivo effect of leuprolide acetate on
      ovarian steroidogenesis.

PMID- 9610464
TI  - Chronic abruption-oligohydramnios sequence.
AB  - OBJECTIVE: To determine outcome in patients with chronic abruption. STUDY DESIGN:
      A retrospective review was performed of all patients delivering at a tertiary
      medical center during a 54-month period. All patients with a diagnosis of
      placental abruption with oligohydramnios or ruptured membranes were included.
      Chronic abruption-oligohydramnios sequence (CAOS) was defined by the following
      criteria: (1) clinically significant vaginal bleeding in the absence of placenta
      previa or other identifiable source of bleeding, (2) amniotic fluid volume
      initially documented as normal, and (3) oligohydramnios (amniotic fluid index <
      or = 5) eventually developing without concurrent evidence of ruptured membranes.
      RESULTS: Twenty-four patients with CAOS were identified. Fourteen had first
      evidence of abruption at < 20 weeks' gestational age. A clot was identified
      between the chorion and uterus in 18/24. The mean gestational age at the first
      bleeding episode was 19.4 +/- 5.5 (SD) weeks, with the mean gestational age at
      delivery 28.1 +/- 4.5 weeks. Preterm premature membrane rupture occurred in
      15/24. In these 15 there was a mean of 11.5 +/- days between the diagnosis of
      oligohydramnios and of ruptured membranes. Patients whose first blood occurred at
      < 20 weeks' gestation delivered at a gestational age of 26.1 +/- 3.9 weeks versus
      33.0 +/- 5.3 weeks for the control group. CONCLUSION: CAOS can occur in
      pregnancies complicated by abruptio placentae. If it develops, the mean
      gestational age at delivery is 28 weeks.

PMID- 9610465
TI  - Screening semen donors for hereditary diseases. The Fairfax cryobank experience.
AB  - OBJECTIVE: To study the carrier frequency of hereditary diseases in potential
      semen donors with no family history of a genetic disease. STUDY DESIGN: Carrier
      screening was performed on potential semen donors for chromosomal abnormalities,
      cystic fibrosis, alpha-1-antitrypsin deficiency, hemoglobinopathies, Tay-Sachs
      disease, Gaucher disease, Canavan disease, and hereditary breast and ovarian
      cancer (the BRCA1 185delAG mutation). The screening regimen used for each donor
      was dictated by his ethnic background. RESULTS: Among 361 individuals screened
      for chromosomal abnormalities, 1 carried an inversion, and 4 were possible
      mosaics. Fifteen of 407 potential donors carried cystic fibrosis, 18 of 209
      carried alpha-1-antitrypsin deficiency, and 2 of 74 carried a hemoglobinopathy.
      No carriers of Tay-Sachs disease (56 screened), Gaucher disease (32 screened),
      Canavan disease (22 screened) or the BRCA1 185delAG mutation (22 screened) were
      found. CONCLUSION: Screening semen donors for a number of genetic diseases that
      are passed silently from generation to generation is warranted since family
      history alone cannot identify them.

PMID- 9610466
TI  - Tension-free vaginal tape. A minimally invasive solution to stress urinary
      incontinence in women.
AB  - OBJECTIVE: To determine the efficacy and safety of a new continence procedure,
      tension-free vaginal tape (TVT) placement for surgical treatment of stress
      urinary incontinence in women. STUDY DESIGN: Eighty-three women with demonstrable
      stress urinary incontinence underwent a nonrandomized, prospective study using
      the TVT procedure. The procedure was previously described by Ulmsten et al. In
      the present study, instead of local anesthesia, epidural blockade with 20 mL of
      2% xylocaine was used. Preoperatively the patients were evaluated with a one-hour
      pad test, full urodynamic testing using either a double-lumen catheter or
      microtip transducer catheter and were instructed to maintain an one-week baseline
      urinary diary one week before and two months after the operation. Another one
      hour pad test and complete urodynamic evaluation using microtip transducer
      catheters were offered to 20 patients postoperatively. The period of follow-up
      ranged from 3 to 18 months. RESULTS: Thirteen women were excluded for various
      reasons; thus, 70 subjects were enrolled in the study. The urodynamic diagnosis
      of the 83 women revealed that 71 had genuine stress incontinence, 11 had mixed
      incontinence and 1 was normal. Mean operation time was 29 minutes (range, 20-51)
      and mean hospital stay 3 days (range, 2-8). Three bladder perforations occurred
      intraoperatively. No patients had intraoperative bleeding > 300 mL, but 11 (16%)
      had blood loss > 200 mL, necessitating an indwelling catheter and vaginal
      tamponade. No evidence of defect healing or rejection of the tape occurred. Urine
      leakage observed on the pad test was significantly reduced from a mean of 63 g
      (range, 10-213) before to a mean of 5 g (range, 0-42) after surgery. The
      objective cure rate was 83%, and the subjective rate was 87%. CONCLUSION:
      Although the follow-up period was short, the TVT procedure seemed to be a safe
      and effective method for the treatment of stress urinary incontinence.

PMID- 9610467
TI  - Alternatively spliced mRNA transcripts encoding the extracellular domain of the
      FSH receptor gene. Expression in the mouse ovary during the ovulatory cycle.
AB  - OBJECTIVE: To evaluate regulation of follicle-stimulating hormone (FSH) receptor
      expression in the mouse ovary during different stages of an artificially induced
      ovulatory cycle. STUDY DESIGN: Follicular maturation was achieved in pubertal
      female mice by pregnant mares' serum gonadotropin (PMSG). Ovulation was induced
      48 hours later by human chorionic gonadotropin (hCG). Ovaries were harvested
      before treatment, at 24 and 48 hours after PMSG and at 3, 9 and 12 hours after
      hCG. RNA was extracted using a single-step isolation method and used for reverse
      transcription. The cDNA was amplified by polymerase chain reaction (PCR) using
      primers designed to amplify a 512-basepair product corresponding to the
      extracellular fragment of the FSH receptor. RESULTS: PCR products, resolved by
      electrophoresis on agarose gels, showed four bands corresponding to four
      discrete, alternatively spliced forms of the FSH receptor. Expression of the
      various transcripts varied at different stages of the ovulatory cycle such that
      the larger transcripts increased up to 48 hours following PMSG and began to
      decrease thereafter, reaching a trough 12 hours following hCG administration.
      Conversely, a smaller transcript reached a peak 9 hours following hCG
      administration and decreased thereafter. CONCLUSION: The various transcripts
      represent different FSH receptor mRNA splicing and may mediate changes in
      receptor function. Since these alternative spliced forms encode different
      portions of the extracellular domain, it is possible that they have altered
      hormone-binding affinity serving a regulatory purpose, such as decreasing hormone
      binding affinity.

PMID- 9610468
TI  - All-fours maneuver for reducing shoulder dystocia during labor.
AB  - OBJECTIVE: To report on a large amount of clinical experience with shoulder
      dystocia managed primarily with the all-fours maneuver. STUDY DESIGN: The all
      fours maneuver consists of moving the laboring patient to her hands and knees.
      Eighty-two consecutive cases of shoulder dystocia managed with this technique
      were reported to a registry through January 1996. RESULTS: The incidence of
      shoulder dystocia was 1.8%, and half of the newborns weighed > or = 4,000 g.
      Sixty-eight women (83%) delivered without the need for any additional maneuvers.
      The mean diagnosis-to-delivery interval was 2.3 +/- 1.0 (SD) minutes (range, 1
      6). No maternal or perinatal mortality occurred. Morbidity was noted in only four
      deliveries: a single case of postpartum hemorrhage that did not require
      transfusion (maternal morbidity, 1.2%), one infant with a fractured humerus and
      three with low Apgar scores (neonatal morbidity, 4.9%). All morbidity occurred in
      cases with a birth weight > 4,500 g (P = .0009). CONCLUSION: The all-fours
      maneuver appears to be a rapid, safe and effective technique for reducing
      shoulder dystocia in laboring women.

PMID- 9610469
TI  - Sixth report of the Joint National Committee on Prevention, Detection, Evaluation
      and Treatment of High Blood Pressure. A summary.

PMID- 9610470
TI  - Intrauterine growth retardation in a woman with primary hyperparathyroidism. A
      case report.
AB  - BACKGROUND: Primary maternal hyperparathyroidism leads to increased serum calcium
      levels, which suppress fetal parathyroid development, leading to hypocalcemia in
      the neonate. CASE: In a pregnant woman, hypercalcemia was observed to be related
      to a parathyroid adenoma that was surgically removed at 15 weeks' gestation.
      Subsequently, hypocalcemia developed, requiring calcium replacement. There was
      marked premature calcification of the placenta, noted to be grade 3 at 23 weeks,
      and this was thought to be related to the severe intrauterine growth retardation
      that later developed. Preterm premature rupture of membranes occurred at 33
      weeks, and a growth-retarded neonate with a small, calcified placenta was
      delivered. CONCLUSION: Pregnancies associated with hyperparathyroidism have been
      found to be complicated by an increased incidence of spontaneous abortion,
      stillbirth and neonatal tetany. There may also be an increased risk of fetal
      intrauterine growth retardation. Serial ultrasonography to evaluate fetal growth
      and antenatal testing should be considered.

PMID- 9610472
TI  - Hemangioma of the ovary. A case report.
AB  - BACKGROUND: Ovarian hemangioma is extremely rare. CASE: We report a case of a 32
      year-old woman who complained of pelvic pain due to a large right adnexal mass.
      On color Doppler sonography the mass showed very rich and complex vascularity,
      with prominent blood flow. A 10 x 8-cm hemangioma of the right ovary was
      resected. CONCLUSION: Hemangiomas should be considered when a richly vascularized
      tumor with prominent blood flow is detected on color Doppler sonography or
      magnetic resonance imaging.

PMID- 9610471
TI  - Eclampsia complicating hydatidiform molar pregnancy with a coexisting, viable
      fetus. A case report.
AB  - BACKGROUND: Eclampsia is a rare and serious complication of pregnancy. The
      occurrence of preeclampsia prior to the 20th week of gestation has been
      associated with concurrent hydatidiform molar pregnancy. We present a case of
      eclampsia complicating a partial molar pregnancy associated with a viable fetus.
      CASE: A 22-year-old white woman, gravida 1, para 0, at 14 weeks' gestation,
      presented with an excruciating headache associated with hypertension, proteinuria
      and a viable intrauterine fetus with gastroschisis. Subsequently the patient had
      a generalized tonic-clonic seizure which resolved with magnesium sulfate therapy.
      Markedly elevated quantitative human chorionic gonadotropin and a moderately
      thickened placenta were the sole clinical features suggestive of a molar
      gestation. Dilation and evacuation was performed revealing unremarkable products
      of conception. Pathologic and cytogenetic analyses revealed a triploid fetus
      (69,XXX) consistent with partial molar pregnancy. CONCLUSION: Development of
      preeclampsia/eclampsia prior to 20 weeks of gestation should prompt a clinical
      evaluation to exclude the possibility of an underlying hydatidiform molar
      pregnancy.

PMID- 9610473
TI  - Ultrasonically dense amniotic fluid in early pregnancy in asymptomatic women
      without vaginal bleeding. A report of two cases.
AB  - BACKGROUND: During the second trimester of pregnancy, the presence of free
      floating particles in the amniotic fluid on ultrasonography has been associated
      with aggregates of cells or fetal blood and with unexplained elevation of
      maternal serum alpha-fetoprotein and the later development of abruptio placentae
      and fetal distress. During the third trimester, particulate amniotic fluid is
      thought to represent meconium or vernix. CASES: An unusual, ultrasonically dense
      appearance of the amniotic fluid was noted prior to 18 weeks of pregnancy in two
      asymptomatic women who carried exencephalic fetuses. In both cases, prenatal
      evaluation of the amniotic fluid suggested that the free-floating particles were
      due to the presence of blood. CONCLUSION: A detailed ultrasonographic evaluation
      should be undertaken should dense amniotic fluid be detected early in pregnancy
      because this sign may help in the early diagnosis of fetuses with congenital
      malformations likely to bleed.

PMID- 9610474
TI  - Late-onset hematometra and hematosalpinx in a woman with a noncommunicating
      uterine horn. A case report.
AB  - BACKGROUND: Noncommunicating uterine horns are rare, occasionally presenting with
      functional endometrial cavities. Surgical removal of the noncommunicating horn is
      commonly performed to prevent endometriosis in these patients. CASE: A 41-year
      old woman with a unicornuate uterus and noncommunicating uterine horn presented
      with a three-month history of right-sided pelvic pain. She had previously
      undergone multiple assisted reproductive technique attempts with superovulation
      and supraphysiologic serum estradiol levels and no apparent symptomatology or
      evidence of hematosalpinx during laparoscopy. Shortly after completing a donor
      oocyte recipient cycle, she developed acute right-sided pelvic pain. Diagnostic
      laparoscopy and subsequent laparotomy confirmed a right hematosalpinx and
      hematometra of the noncommunicating horn, with stage III endometriosis.
      CONCLUSION: Consideration of prophylactic resection of a noncommunicating uterine
      horn with a cavity should be considered in an asymptomatic, reproductive-age
      patient with this rare mullerian anomaly.

PMID- 9610475
TI  - Intramural pregnancy with negative maternal serum beta-hCG. A case report.
AB  - BACKGROUND: Intramural pregnancy is the rarest form of ectopic pregnancy. The
      diagnosis depends upon the sonographic finding of intramural gestational sac-like
      growth and persistent high beta-human chorionic gonadotropin (beta-hCG) levels
      after dilatation and curettage. No authors mentioned negative beta-hCG result in
      such situation. Rarely has the literature contained preoperative sonograms and
      photographs of postoperative gestational tissue. CASE: A 31-year-old woman
      presented with vaginal spotting for five months. Six months earlier she underwent
      dilatation and curettage for blighted ovum at 8 weeks' gestation. Since then,
      incidental vaginal spotting was noted. Sonography demonstrated an intramural cyst
      with fetal pole-like growth. Serum beta-hCG, diagnostic dilatation and curettage,
      and hysteroscopic examination were negative. Laparotomy for excision of the cyst
      confirmed an intramural pregnancy. CONCLUSION: Because of the long period after
      fetal wastage, negative serum beta-hCG was noted in this case. Negative serum
      beta-hCG was unreliable in the exclusion of intramural pregnancy. With the
      sonographic appearance of intramural gestational sac-like growth, in spite of a
      negative serum beta-hCG the clinician should be alert to the possibility of
      intramural pregnancy.

PMID- 9610476
TI  - [Ultrastructure of conducting and working myocytes in papillary muscles of the
      heart of intact rabbits].
AB  - The quantitative and qualitative ultrastructural analysis of specialized
      conducting and working myocytes in papillary muscles of the rabbit heart was
      made. The volume fractions of myofibers, mitochondria, nuclei, lipids, vacuoles,
      glycogen, sarcoplasmatic reticulum, T-tubules, lysosomes, and "clear" cytoplasm
      of conducting and working myocytes were estimated in addition to cell diameters.
      The results were compared with literature data for the Purkinje cells of
      different mammals. Principles of morphological description of conducting and
      working myocytes, allowing to recognize these cells in different parts of the
      heart and to compare them in different animals, are discussed.

PMID- 9610477
TI  - [Morphologic and functional characterization of human aortic endothelium. III.
      Growth in culture and colony formation at low seeding density].
AB  - In human aortic endothelial cell (HAEC) cultures, obtained separately from aortic
      zones of low (LP) and high (HP) probability of atherosclerosis, proliferative
      characteristics of cells and HAEC ability to form colonies at clonal seeding
      density were studied. It has been found that the population doubling time is
      significantly higher in endothelial cell (EC) cultures from HP-zones, compared to
      that in cultures from LP-zones of the same vessels. In cultures from both LP- and
      HP-zones only a few percent of EC had a proliferative potential enough to form
      cell colonies. The number of formed colonies was always lower in EC cultures from
      HP-zones, and decreased depending on atherosclerotic lesions and cell donor age.
      The obtained data suggest that the decline of EC proliferative potential, mostly
      in HP-zones (even without visible signs of atherosclerotic lesions) is due to a
      decrease in the number of cells with a high mitotic activity, i.e. "cambial"
      cells.

PMID- 9610478
TI  - [Rehabilitation of the hepatocyte glycogen-forming function in the rat cirrhotic
      liver due to carbohydrate rich diet].
AB  - By cytofluorometric and biochemical methods the content of total glycogen and its
      fractions was investigated on the smears of isolated liver cells: labile fraction
      (LF) and stable fraction (SF) and also activities of glycogen phosphorylase (GP),
      glucose-6-phosphatase (G-6-Pase) and glycogen synthase. The material was obtained
      from serial liver biopsies from each investigated animal prior to CCl4 action
      (control), with cirrhosis (6 months of CCl4 poisoning) and 1, 3 and 6 months
      after CCl4 poisoning was finished. It was shown that chronic CCl4 poisoning
      induced a typical liver cirrhosis accompanied with the 2-3 times increase in the
      total glycogen content, in comparison with the norm, with the decrease in LF to
      53%, and also with the fall of G-6-Pase and GP activities by 82 and 25%, resp.
      After 1, 3 and 6 months following poisoning cessation, the lobule structure,
      infringed due to cirrhosis, was not restored. But functional parameters of the
      cirrhotic liver were seen gradually recovering without CCl4 poisoning. The
      application of carbohydrate rich diet favoured a most complete rehabilitation:
      the content of total glycogen and its fractions and the activity of G-6-Pase and
      GP returned to the normal level.

PMID- 9610480
TI  - [The interaction of prosomes with fibrillar actin].

PMID- 9610479
TI  - [Growth of stable clones of mouse fibroblast cell line C3H10T1/2 expressing the
      human retinoblastoma gene product].
AB  - Phosphorylation and dephosphorylation of the retinoblastoma gene product (pRB)
      are recognized as necessary events in the cell cycle progression. To study the
      role of pRB in regulation of cell proliferation, the stable cell lines with
      constitutive expression of the exogenous RB gene can be employed. In order to
      obtain such cell lines in this work C3H10T1/2 mouse fibroblasts were infected
      with defective retrovirus encompassing the RB and Neo gene conferring resistance
      to geniticine (G418). The pRB production and its phosphorylation pattern were
      analyzed by immunoblotting in cell lysates considering well known data on
      correlation between pRB phosphorylation pattern and its electrophoretic mobility.
      Cell lines subjected to G418 selection with the following cloning procedure were
      identical to the control cells expressing beta-galactosidase, when compared for
      pRB production and phosphorylation in the cell cycle stages characterized by
      hyperphosphorylated pRB. However, cells of the experimental cell lines
      hypophosphorylated pRB much faster and accumulated much more underphosphorylated
      protein compared to the control cell lines. The doubling time of the cells was
      not affected either by changes in the pRB phosphorylation pattern or by its
      overproduction during separate cell cycle stages. These results suggest that
      maintaining of the physiological level of pRB phosphorylation in cycling cells is
      strictly controlled and is considered to be a more important condition of the
      cell cycle progression than pRB dephosphorylation.

PMID- 9610481
TI  - Effect of human alpha2-macroglobulin on proliferative activity of rat tumor
      cells.
AB  - The Walker carcinosarcoma cells were cultured in the medium with low
      concentration (0.25%) of fetal calf serum, in the presence of native or
      methylamine-treated (modified) human alpha 2-macroglobulin (alpha 2-MG) in vitro.
      The proliferative activity (3H-thymidine incorporation) of these cells increased
      in the presence of one or the other alpha 2-MG preparation. It allows to suppose
      that the human alpha 2-MG may serve as a growth-stimulating factor of tumour
      cells.

PMID- 9610482
TI  - [Dependence of the process leading to phosphorylation of retinoblastoma protein
      (pRb) on the status of the actin cytoskeleton].
AB  - It has been confirmed that the main actin-dependent period of G1 phase of the
      cell cycle is the middle of G1. As the critical points in G1 phase are associated
      with the synthesis of cycling D and E and with the formation of their active
      complexes with cyclin-dependent kinases (Cdk's), a study of a possible influence
      of actin filaments on these processes was performed. The activity of G1 kinases
      was estimated by the degree of phosphorylation of their specific substrate
      retinoblastoma protein (pRb). Immunoblot analysis with specific antibodies to pRb
      revealed hypophosphorylated from of Rb in lysates of resting Swiss 3T3 cells and
      the appearance of hyperphosphorylated form after 12 h of EGF and serum
      stimulation. In was shown that actin filaments distruction by H2CB led to a
      decrease in hyper phosphorylated form appearance, depending on the depth of
      resting state of the cells and efficiency of their stimulation by growth factors.
      Thus, these data may suggest the involvement of actin cytoskeleton in functioning
      of the transcription chain cyclin/Cdk-R1-E2F.

PMID- 9610483
TI  - [Modification of cell damage, caused by variable rate heating, by means of
      changes in osmotic pressure of the medium or using chloramphenicol].
AB  - We investigated the influence of media with different osmotic pressure and of
      chloramphenicol on cytotoxic effects of heating with different rate of
      Escherichia coli B/r and Escherichia coli Bs-1 bacteria, and Zygosaccharomyces
      bailii yeast cells. It was shown that the hypotonic media appreciably increased
      cytotoxic action of heating with different rate, and, on the contrary, the
      hypertonic media inhibited induction of these effects. The inhibitor of protein
      synthesis chloramphenicol was established not to affect the bacterial
      thermoresistance in the process of different heating rate. On the basis of
      analysis of the obtained and literature data, it is proposed that a reason of
      cell injury dependence of the heating rate may be the availability of dissimilar
      levels of osmotic homeostasis destabilization in these cells when heated with
      different rates.

PMID- 9610484
TI  - [Association of phosphoinositide-specific phospholipase Cgamma1 with elements of
      cytoskeleton in A-431 cells].
AB  - It is shown that phosphoinositide-specific phospholipase C gamma 1 (PLC gamma 1),
      a substrate of growth factor receptors, is associated with cytoskeleton in A-431
      cells. PLC gamma 1 is co-localized only with the cortical actin but not with
      actin stress fibers. Since EGF receptor is also co-localized with the cortical
      actin it is concluded that PLC gamma 1 co-localized with actin is mediated by the
      EGF receptor. After the treatment with cytochalasin B PLC gamma 1 is co-localized
      with actin aggregates and cytoskeleton elements other than actin. Using double
      immunofluorescence PLC gamma 1 is shown to be associated with cytokeratin
      intermediate filaments. The cross-talking of different cytoskeleton elements and
      their participation in cell signaling is discussed.

PMID- 9610485
TI  - [Internal symmetry and repetitive sequences in the primary structure of IRS
      proteins, endogenous substrates of insulin receptor].
AB  - A new method is developed for identification of mirror type internal symmetry in
      protein primary structures (named as method of internal symmetry scanning). As
      distinct from our earlier developed graphic method, the application of the new
      method allows, to identify enough fast and effective, symmetrical segments in
      proteins of any length, and to determine the type of internal symmetry centres
      (one or two amino acid residues). By this method the structure of IRS-proteins,
      endogenous substrates of tyrosine kinase receptors, was analysed. It has been
      shown that the density of internal symmetry centre distribution and the homology
      of antiparallel sequences in functionally important regions, which possess
      conservation of the primary structure (the conservative profile for IRS1-proteins
      was calculated in this work), are higher in comparison with the variable regions.
      Groups of repeating sequences in the primary structure of IRS1-proteins are
      found. The localization of the repeats coincides with one of symmetrical
      structures. These findings are in line with Chipens' hypothesis in which he
      established a correlation between the internal symmetry and the homologous
      repeats.

PMID- 9610486
TI  - [Cytogenetics. Science and people].
AB  - Some little-known facts are presented about foundation of the Institute of
      Cytology, Academy of Sciences of the USSR (now of Russia). The advancement of
      main lines investigation in the field of cytogenetics, carried out at the
      Institute from its inception up to now, has been traced, with special attention
      being called to organization of a scientific school of cytogenetics.

PMID- 9610487
TI  - Effect of nickel chloride on mouse T-lymphocyte subsets.
AB  - The study was carried out to observe the effect of nickel chloride (NiCl2) on T
      lymphocyte subsets, CD4, CD8 and CD4/CD8 ratios in vivo. BALB/C mice were
      injected i.p. with NiCl2 every other day for 2 w. The NiCl2 doses were 1, 3, 6, 9
      or 12 mg/kg. Lymphocytes were obtained from mouse spleen and cultured in the
      presence of monoclonal antibody FITC conjugated, anti-CD4 or anti-CD8. Samples
      were determined with a flow cytometer. A suppressive effect on CD4-positive cells
      was found in the 6 mg/kg group, but this subset was restored to the control level
      in the 9 and 12 mg/kg groups, suggesting that there was an "immune tolerance"
      effect. No significant changes were found in CD8-positive cells and CD4/CD8
      ratios. The results suggested the NiCl2 had a deleterious effect on mouse T
      lymphocytes in short-term in vivo exposure, but the effects may depend on the
      dose and cell subset.

PMID- 9610488
TI  - Experimental intoxication by Myoporum laetum in sheep.
AB  - Myoporum laetum was collected in the municipalities of Rio Grande and Capao do
      Leao in winter and in Santa Vitoria in summer, autumn, winter and spring, in the
      state of Rio Grande do Sul, Brazil, and in the Department of Rocha, Uruguay, in
      winter and spring. The fresh green plant was fed to 17 sheep. All sheep developed
      clinical signs, except 1 that consumed only 4 g/kg bw daily during 10 d. Five of
      the 9 sheep dosed with 40 g/kg died. Four sheep dosed with plants from Uruguay at
      40 g/kg, 6 sheep dosed with 20 g/kg, and 1 sheep dosed with 2 daily doses of 8
      g/kg survived. Clinical signs were anorexia, restlessness, ruminal stasis,
      jaundice and dry feces with mucus or blood. All surviving sheep had
      photodermatitis in the face, ears, eyes and lips. Histologic lesions were
      characterized by periportal liver necrosis. Serum levels of AST, GGT and
      bilirubin were increased. M laetum from Uruguay was less toxic, suggesting a
      variation in toxicity among plants from different regions.

PMID- 9610490
TI  - Clenbuterol residues in non-liver containing meat as a cause of collective food
      poisoning.
AB  - beta 2-adrenergic agonists, particularly clenbuterol, are illegally used as
      growth promoters to obtain lean in meat. Their administration in feedlots can
      constitute a severe risk for animal welfare and exposes consumers to involuntary
      drug consumption at pharmacological active concentrations. Reported poisoning
      episodes have been associated with the consumption of beef liver where
      clenbuterol residues concentrate. In August 1996, 62 persons asked for medical
      help at the emergency rooms of 2 hospitals near the city of Caserta (Italy).
      Their clinical profile was characteristic of previously occurring clenbuterol
      intoxication, which reported superventricular extrasystoles and atrial
      fibrillation. All patients had non-liver beef meat consumption 10-30 min to 2-3 h
      before symptoms developed. An ELISA screening test specific for clenbuterol
      confirmed the drug's presence. Definitive confirmation of clenbuterol and
      determination of the drug content in meat samples were obtained by GC-MS, using 2
      different derivatization. Concentrations in the meats ranged from 0.8 to 7.4
      mg/kg. These analytical data provided evidence of the seriousness of the
      poisoning and helped the National Health System identify other possible
      misinterpreted cases. This case demonstrates that clenbuterol poisoning can also
      occur after consumption of beef meat other than liver.

PMID- 9610489
TI  - Does anti-atherogenic estradiol valerate treatment cause adverse effects on liver
      and uterus in NZW rabbits?
AB  - The rabbit has been a widely accepted animal model for atherosclerosis research
      since Anitschkow first used this animal in 1913 in identifying dietary-induced
      hypercholesterolemia as a major risk factor for atherogenesis. Experiments with
      cholesterol-fed rabbits have demonstrated the beneficial effects of estrogen
      treatment on the development of atheroma for more than 50 y. Clinical trials have
      found a reduction in cardiovascular events of up to 50% in postmenopausal women
      receiving estrogen replacement therapy. However, metabolic conditions in rabbits,
      as well as physiological estrogen serum levels, differ in some aspects from those
      in humans. In rabbits, experimentally-induced hormone levels are about 5- to 10
      fold higher than those found in untreated animals. Normal physiological estrogen
      levels in rabbits are not cardioprotective under dietary-induced
      hypercholesterolemia. We investigated whether replacement induced
      "hyperestrogenemia" causes adverse effects on organs other than the
      cardiovascular system. Twenty-nine female rabbits were divided into 4 different
      groups, 2 without and 2 with estrogen treatment (1 mg estradiol valerate/kg body
      weight/w over 12 w). Organ weights, transaminases and uterine histology were
      examined. In rabbits treated with estrogen, we did not see relevant adverse
      effects on heart, kidney and liver weights, or on liver enzymes. But there was a
      significant increase in spleen weights, as well as notable changes in the
      endometrium with moderate inflammation. These findings indicate that the dosage
      of estrogen commonly used for atherosclerosis research does not cause serious
      disorders in the major organs of cholesterol-fed rabbits.

PMID- 9610491
TI  - Intoxication by Xanthium cavanillesii in cattle and sheep in southern Brazil.
AB  - Three outbreaks of Xanthium cavanillesii intoxication occurred in the spring in
      the State of Rio Grande do Sul, southern Brazil. All outbreaks were observed in
      paddocks with sandy soils in flood plains along water streams. The paddocks had
      been under water, and after water withdrawal cattle were introduced to those
      areas which had seedlings of X cavanillesii and shortage of other forage.
      Mortality varied between 3 and 58%. Most animals were found dead or died a few
      hours after observation of clinical signs. The main lesion was a swollen liver
      with acute diffuse centrilobular necrosis. The disease was produced
      experimentally by feeding cotyledons at 0.75 and 1% bw in calves, and at 1.5 and
      2% bw in sheep. Clinical signs and gross and microscopic lesions were similar to
      those observed in field cases. X cavanillesii in the 4-leaf stage with the
      attached cotyledons was also toxic for cattle and sheep, but the same plant
      without cotyledons lost its liver toxicity. The lethal dose of cotyledons divided
      in 5 daily doses was not toxic for cattle and sheep, demonstrating the non
      cumulative effect of the plant.

PMID- 9610492
TI  - Bovine arsenic toxicosis from ingestion of ashed copper-chrome-arsenate treated
      timber.
AB  - Arsenic toxicosis is reported in a variety of animal species. It occurs most
      commonly in cattle and ranks second only to lead as a cause of heavy metal
      poisoning. We describe a case of arsenic toxicosis attributable to ingestion of
      ashes from burned posts treated with an arsenic-containing preservative. Burning
      of the posts concentrated the arsenic and rendered lethal a product normally used
      around livestock. Lack of normal salt supplementation to the herd was conducive
      to pica-like behavior and ingestion of toxic ashes. Rapid diagnosis led to
      removal of the arsenic source and limited losses to 4 cows.

PMID- 9610493
TI  - Clinical experience with pendimethalin (STOMP) poisoning in Taiwan.
AB  - The herbicide pendimethalin (STOMP) shares a similar chemical structure with
      nitro compounds such as dinitrobenzene, which was previously demonstrated to
      cause methemoglobinemia in mammals. However, reports on STOMP poisoning in humans
      are rare. We reviewed 71 STOMP poisoning cases (42 men and 29 women of mean age
      43.9 +/- 2.5 y) reported to the Poison Control Center--Taiwan from September 1986
      to September 1997 and summarized their clinical manifestations. Two incidences
      resulted from skin and eye contact. The rest were due to oral ingestion
      intentionally or accidentally. The average ingestion was 106.1 +/- 13.4 ml. Among
      them, 20 cases had no symptoms or signs, 38 had mild effects such as nausea,
      vomiting and sore throat, 7 had effects such as severe retching, hematemesis and
      seizures. Four patients expired due to also taking other herbicides (mainly
      organophosphates) and because of inadequate airway management. Adequate
      ventilation support was the major therapy in salvaging the poisoning cases.

PMID- 9610494
TI  - Malicious paraquat poisoning in Oklahoma dogs.
AB  - Paraquat is a restricted use herbicide which is extremely toxic to companion
      animals when ingested. This report details one incident of malicious poisoning
      involving 6 dogs. All dogs were from the same geographic area, and 5 had
      pulmonary and renal lesions consistent with paraquat toxicosis. Diagnosis was
      initiated by a modified dithionite spot test on vomitus from 1 dog. Subsequent
      tissue paraquat levels ranged from non-detectable to 1 ppm.

PMID- 9610495
TI  - Postmortem diagnosis of accidental cocaine intoxication in a dog.
AB  - Despite an abundance of data on the experimental effects of cocaine in dogs, no
      detailed reports documenting accidental cocaine exposure in domestic pets have
      been reported in the veterinary literature. A case of cocaine intoxication is
      described in a 19-mo-old male catahoula hound in which the diagnosis was
      confirmed using histopathology, thin-layer chromatography and mass spectrometry.
      The case was presented as a possible intoxication of unknown etiology. Routine
      toxicologic screens and characteristic histologic lesions provided evidence for
      the diagnosis without prior suspicion of cocaine involvement.

PMID- 9610496
TI  - Ibuprofen, aspirin and acetaminophen toxicosis and treatment in dogs and cats.
AB  - Toxicosis to 3 commonly available analgesics--ibuprofen, aspirin and
      acetaminophen--occurs in dogs and cats after acute ingestion or repetitive
      administration of therapeutic or excessive doses. Whereas in acute exposure,
      where the clinical course of an overdose to all 3 drugs is predictable in
      relation to the amount ingested, in chronic exposure to therapeutic doses of
      aspirin and ibuprofen, the development of gastric ulcers and analgesic
      nephropathy is unpredictable. Ibuprofen is not recommended for prolonged
      treatment in dogs and cats due to the likelihood of ulcer formation. Although
      gastric mucosal adaptation usually occurs with repeated therapeutic doses of
      aspirin, some individuals nevertheless develop gastric ulcers; simultaneous
      administration of the prostaglandin analogue misoprostol can reduce the risk.
      Following acute ingestion of aspirin or ibuprofen, treatment is essentially
      symptomatic and supportive following early decontamination procedures.
      Gastrointestinal protectants and i.v. fluids with sodium bicarbonate are
      generally recommended. Acetaminophen toxicosis is usually associated with single
      acute ingestion, and the primary target organs affected are the liver and the red
      blood cells in dogs and cats respectively. Because signs can progress rapidly
      with acute acetaminophen overdose, administration of N-acetylcysteine is always
      recommended, even when the history is unclear. This report summarizes the common
      clinical presentations of dogs and cats exposed to therapeutic or excessive doses
      of ibuprofen, aspirin or acetaminophen, and describes the treatment procedures
      advised by the ASPCA-National Animal Poison Control Center.

PMID- 9610497
TI  - Client satisfaction with the New Zealand National Poisons Information Service.
AB  - A telephone survey of a random sample of callers to the New Zealand National
      Poisons and Hazardous Chemicals Information Centre (NPC) was undertaken to assess
      public satisfaction with, and knowledge of, the NPC and to determine whether the
      NPC was meeting the needs of its users. The response from a sample of 433
      individuals (354 members of the general public and 79 health professionals) was
      79%. Maori and Pacific Island people were under--represented in the sample.
      Overall the level of satisfaction with the NPC was high with 91% of the
      respondents finding the information they received very useful. If the NPC had not
      been available, 81% of the public would have sought advice from a medical
      facility and 59% would have visited such a facility. It was estimated that the
      NPC could be saving the public health services in New Zealand (NZ) up to NZ $1.3
      million annually. It was concluded that the NPC was meeting the needs of current
      users, although greater public awareness and improved access are needed
      particularly for Maori and Pacific Island people.

PMID- 9610498
TI  - Deaths from pesticide poisoning in Spain from 1991 to 1996.
AB  - Data on 184 deaths from pesticide poisonings that occurred in Spain from 1991 to
      1996 have been collated via a survey from the National Institute of Toxicology,
      Sevilla. Organophosphates and carbamates accounted for the majority of the cases.
      Other substances involved were organochlorines such as endosulfan and the
      herbicide paraquat.

PMID- 9610499
TI  - [Areas, findings and possible interventions in psychogeriatric research].

PMID- 9610500
TI  - [Interventional gerontology in German-speaking countries: a social and behavioral
      science assessment].
AB  - This work is aimed at reviewing 20 years of gerontological intervention research
      within the social and behavioral domain in German speaking countries. Only
      controlled studies based on adequate measurement instruments are considered.
      Literature analyses reveal that the issue of cognitive intervention research is
      well-covered, underlining clear positive training effects in intellectual
      performance and memory. Also, studies on the limits of mental capacity represent
      a highlight of German cognitive training research. Another bunch of studies
      underlines the potential of different intervention to enhance independence in day
      to-day function, social activity, and subjective well-being. Positive effects in
      self-concept, personal control, and attribution style are as well reported. A
      general discussion of this body of work leads to suggestions for future research
      priorities.

PMID- 9610501
TI  - [Speed of information processing and fluid intelligence in advanced age. A
      secondary analysis of data of the Bonn Longitudinal Study of Aging based on
      "latent growth curve models"].
AB  - According to the "speed"-hypothesis of cognitive development, the slowing of
      information processing in old age is at the core of negative age differences in
      psychometric intelligence. The present study investigates the "speed"-hypothesis
      for fluid intelligence at the individual level using Latent Growth Curve
      Methodology. Data on 4 measurement points come from the Bonn Longitudinal Study
      of aging (N = 127, mean age 67.2, 53% women). Based on principal factor analysis,
      markers of mental speed were the WAIS Digit Symbol Test and a simple psychomotor
      task. As indicators of fluid intelligence the WAIS Object Assembly and Block
      Design were used. After separately fitting Latent Growth Curve Models for the
      trajectory of mental speed and fluid intelligence, a combined model showed no
      statistically significant improvement of fit for freeing the covariance between
      the two slope-factors. Interpreting this result, contrary to the "speed"
      hypothesis the intraindividual change of fluid intelligence does not relate to
      the according change of mental speed.

PMID- 9610502
TI  - [Modular memory training for elderly adults: concept and evaluation].
AB  - We present a modular concept of a cognitive training relevant to the demands of
      everyday life of community dwelling older adults. The concept has three major
      advantages. First, it takes into account the current performance levels and needs
      of the trainees. Second, the training is economical in aiming at selecting the
      most effective training elements. Third, the concept allows the evaluation of
      single elements of the training. The application of this concept points at the
      importance of training content being relevant to trainees' everyday lives.
      Results indicate that training effectiveness depends on the starting level of
      performance and the cognitive domain being trained. Overall, the results
      demonstrate the possibility to maximize training gains of older adults by
      designing adequate trainings for well-defined subgroups of normal older adults.

PMID- 9610503
TI  - [Constant social and spatial environment in aging: memory theory, case examples,
      practice relevance].
AB  - An ecological theory of remembering is formulated which is based on the patterns
      of meaningfulness in the social and spatial environment. The specific ecological
      relationship to the environment is affinitive, and also opens access to the
      resources of the past. In the present study, conditions for this access (in
      particular with older people) were investigated. It is assumed that older people,
      especially, when they lose someone with whom they had a fixed relationship seek
      counselling and that abrupt changes in the spatial environment, such as moving to
      a home, are rejected by older people. These hypotheses were checked on the basis
      of material (N = 120) gathered in a counselling service for the aged and they
      were essentially confirmed. To make matters clear, "typical" and thus every-day
      experiences of maintenance and loss of competence are cited from the material.
      Finally, practical conclusions are drawn with regard to work with the aged.

PMID- 9610504
TI  - [Behavior therapy competence training--a specific intervention with beginning
      Alzheimer dementia].
AB  - At the Psychiatric Department, Ludwig-Maximilians-Universitat, Munich, a
      behavioral competency training (Verhaltenstherapeutisches Kompetenztraining) VKT
      is offered to patients with early stages of Alzheimer's disease (AD). The primary
      objects of VKT are, (a) patient support in coping with the diagnosis of AD, (b)
      mobilization of the present personal activity resources, and (c) minimization of
      depressive symptoms. The VKT consists of six therapy-modules: 1. behavior
      analysis, 2. psychoeducation, 3. stress management, 4. increase of pleasant
      activities, 5. enhancement of social competency, and 6. modification of
      depressive cognitive patterns. The VKT is derived from scientific findings that
      show the involvement of psycho-social factors in the genesis of AD. Inadequate
      coping-behavior, unescapable stress and resulting neurodegenerative effects, a
      low premorbid niveau of activity and the presence of premorbid depressive
      symptoms outline the necessity of psychotherapeutic treatment in AD patients.

PMID- 9610505
TI  - [Effects of psychosocial and psychotherapy interventions on well-being and self
      concept in advanced age--results of meta-analyses].
AB  - Effects of 94 different psychosocial and psychotherapeutic interventions on well
      being in the elderly were meta-analyzed. Psychological well-being was improved
      and self-rated depression decreased for about half a standard deviation. The mean
      effect size for other-rated depression reached d = 1.15. Whereas age of
      participants did not correlate with change in self-rated well-being or
      depression, other-rated depression improved less in older samples. High effect
      sizes derived from control-enhancing interventions and behavior therapy. Sub
      analyses showed that individual setting produced higher improvement than group
      setting. Higher "therapeutic" qualifications and interventions in nursing homes
      were associated with higher effect-sizes too. Implications for planning
      interventions in old age are discussed.

PMID- 9610506
TI  - [Patterns of perception of work status: a contribution to innovative capacity of
      elderly workers].
AB  - Current demographic trends indicate an increase in average age within the
      workforce. The "junior-staff-directed" personnel strategies of companies
      obviously no longer fit when the number of older workers increase. Based on
      current research, it is still open in which direction older employees present an
      obstacle for innovation and which intervention strategies are necessary to
      promote their ability for innovation. This study particularly indicates the
      subjective view of older workers regarding various aspects of their current job
      situation. Data collection is based on semi-structured interviews with 75
      participants (49 men, 26 women, 45 to 55 years old) working in companies of
      chemical industries in Germany. Results show that older workers have different
      perceptions of their job situation. One group feels to be "successful and
      socialintegrated", a second group of older workers "adjusts itself passively to
      job demands", and a third group is "complaining and not satisfied with the
      current job situation". Indicators for innovation abilities are "to be able to
      set goals", "acceptance of challenges" as well as the "acceptance to take over
      responsibility". In addition aspects of the working conditions and the degree of
      job-training discriminated between the three groups. The findings point to a
      close relationship between "innovation capability" of older workers and
      "stimulating working conditions"; conclusions for personnel strategies can be
      drawn.

PMID- 9610507
TI  - [Recall of traumatic life events at the time of national socialism in (former)
      Jewish emigrants and concentration camp prisoners].
AB  - Semi-structured interviews with 248 (former) Jewish emigrants and extermination
      camp survivors in Germany and three destination countries of Jewish emigration
      (Argentina, Israel, United States) indicate that reminiscence of traumatic
      experiences suffered from National Socialist Germany occurs in numerous daily
      contexts. In later life, traumatic memories do not only occur spontaneously and
      unexpectedly; moreover, they are an essential part of the people's frame of
      reference for questions about personal identity, perceptions of social
      relationships, society and societal development, and coping with specific themes.
      Following a pilot study on subjective reconstruction of the life course in
      (former) Jewish emigrants and extermination camp survivors, different phases of
      post-holocaust development are distinguished. Self-ratings for intensity of
      traumatic reminiscence for these phases of personal development support the
      hypothesis that traumatic reminiscence increased in old age. People highly differ
      in coping with stressful reminiscence. Some study participants react with
      depression, anxiety, feelings of survivor guilt, and withdrawal from social
      relationships. Others, however, are highly engaged in social relationships,
      especially with the following generations. They want to give a contribution to
      the educational work of their society and to prevent discrimination, racism, and
      xenophobia.

PMID- 9610508
TI  - [Duplex ultrasound risk stratification of percutaneous puncture of the brachial
      artery for diagnostic and interventional coronary angiography].
AB  - Diagnostic and interventional heart catheterization in peripheral vascular
      disease often requires due to iliacal disease additional methods of arterial
      approach besides the Judkin's technique. The percutaneous catheterization of the
      brachial artery finds widespread use. A major complication linked with this
      method is an increased rate of thrombotic occlusions at the puncture site. Thus,
      we investigated in a prospective set-up the ability of duplex ultrasound to
      identify predictive risk factors for vascular complications. Over a period of 20
      months, 8000 patients referred to heart catheterization were studied. Routine
      catheterization via the femoral route was contraindicated in 34 out of 8000
      mostly due to severe peripheral vascular disease with multiple vascular risk
      factors (diabetes, hypertension, and smoking). 53 patients who had a comparable
      low risk-profile served as the control group. The brachial artery was examined by
      ultrasound duplex for vessel anatomy and diameter at the puncture site before
      coronary angiography. Both groups (patient and control group) showed in 15% a
      variable anatomy with a premature division of the brachial artery in 6% proximal
      of the elbow and in 9% already distal to the axillary artery. Because of reduced
      diameters of these variable vessels no procedure was carried out at these arms.
      In all cases the opposite arm was successfully used instead, because the variants
      were always located only at one arm. The diameter of the brachial artery measured
      in average 5.0 +/- 0.8 mm and 4.8 +/- 0.7 mm in patients and controls,
      respectively. Women had a significantly smaller vessel diameter than men,
      measuring a difference of 0.4 and 0.6 mm, respectively (p < 0.05). For coronary
      angiography 6F and 7F arterial sheats were used equally, and in 32% of all cases
      a coronary intervention was performed. 31 (91%) procedures were carried out
      without complications; there was a false aneurysm in 1 patient (3%) and an
      occlusion of the brachial artery at the puncture site in 2 patients (6%). The
      occluded vessels of two diabetic women had a reduced diameter at the level of 10%
      of the standard distribution and an unfavorable ratio of sheat-to-vessel-diameter
      which lead initially to an obstruction of nearly 50% of the vessel lumen during
      catheterization. Screening of the brachial artery by ultrasound duplex before a
      percutaneous catheterization for coronary angiography and intervention showed
      reproducibly the variable anatomy and differences in vessel diameter, which can
      be risk factors for thrombotic occlusion. Important details for the location of
      the puncture site and the possible size of the arterial sheat can be obtained, so
      that coronary interventions with 7F catheter systems are still practicable. This
      technique is a simple and efficient method to estimate the relative risk of
      arterial occlusion prior to percutaneous puncture of the brachial artery,
      especially in a group of patients with severe atherosclerosis and elevated
      vascular risk-factors.

PMID- 9610509
TI  - [Measuring bioelectric myocardial impedance as a noninvasive method for diagnosis
      of graft rejection after heart transplantation].
AB  - 12 beagle dogs underwent neck-heart transplantation and were immunosuppressed
      with cyclosporine and methylprednisolone. Intramyocardial impedance was
      determined twice daily with four screw-in electrodes in the right and left
      ventricle. Transmyocardial biopsies and the intra-myocardial electrogram (IMEG)
      were performed as reference methods. 19 rejection episodes were induced. When
      acute rejection was seen in histology the animals were treated with pulsed 125 mg
      methylprednisolone over 5 consecutive days and immunosuppression was raised to
      sufficient levels. Successful treatment of rejection was controlled by biopsy.
      All hearts showed a uniform decrease of impedance of about 28.3% +/- 5.5%
      immediately after implantation, then reaching a stable plateau after 7 to 8 days.
      Impedance values then remained unchanged as long as rejection was absent. Biopsy
      findings of grade 1A to 1B (ISHLT) were accompanied by a statistically
      significant increase of impedance of 12.2% +/- 2.5%, of grade 2 to 3A of 19.2% +/
      3.2%, and of grade 3B to 4 of 27.0% +/- 2.9%. Sensitivity was 95%, specificity
      91%. Successful treatment of rejection led to a uniform decrease of impedance to
      intramyocardial impedance for high frequencies can reliably indicate alterations
      of the cell membrane and the intracellular space during acute cardiac allograft
      rejection. The amount of increase of impedance is a reliable noninvasive
      parameter to graduate acute cardiac allograft rejection. The success of treatment
      of rejection can also be monitored by impedance. This noninvasive method is
      applicable for telemetric rejection monitoring via an implantable device, which
      would allow continuous rejection surveillance of a patient at home without
      hospital admission.

PMID- 9610510
TI  - [Evaluation of a rapid qualitative test for cardiac troponin T in clinical
      diagnosis of patients with acute coronary syndrome].
AB  - OBJECTIVE: To evaluate the practical performance and the diagnostic power of a
      rapid, qualitative assay for the detection of cardiac Troponin T (indicated cut
      off level: 0.3 ng/ml) in EMS patients presenting with acute myocardial ischemia.
      PATIENTS: 145 consecutive patients with non-traumatic chest pain treated by the
      Mobile Intensive Care Unit team. During phase 1 (73 patients), blood drawn at the
      emergency site was used to perform a Troponin T rapid assay under defined
      conditions at the hospital. During phase 2 (72 patients), the rapid assay was
      already performed at the emergency site. RESULTS: In phase 1 all tests were
      performed correctly, whereas 5.6% of the test results had to be declared invalid
      in phase 2. 17 (11.7%) of the 145 patients showed a positive test result.
      Analytic sensitivity was 100%, specificity 96.3%. 37 of the 145 patients (median
      duration of symptoms: 150 minutes) showed a myocardial infarction (MI). Related
      to the diagnosis of MI diagnostic sensitivity, specificity, positive and negative
      predictive values were 35.1, 96.3, 76.5, and 81.3%. Mortality in patients with a
      positive rapid assay was 35.3%, compared to 6.3% in patients with a negative test
      result (p < 0.001). CONCLUSIONS: The rapid assay allows the detection of Troponin
      T in concentrations above the cut-off level. Meticulous observance of the
      manufacturer's rules is imperative. A single preclinical rapid assay does not
      allow to exclude a MI. However, the test enables EMS personnel to identify
      patients who are at increased risk of dying from an acute coronary syndrome in
      the immediate future.

PMID- 9610511
TI  - [Surgery of acute aortic valve endocarditis: prognosis in paravalvular abscess].
AB  - The occurrence of paravalvular abscesses in the course of an acute endocarditis
      of the aortic valve indicates an advanced stadium of the disease. The infection
      has spread beyond the limits of the valve leaflets, and ongoing destruction of
      the paravalvular tissue is to be expected, if the endocarditis is continually
      treated by antibiotics alone. Surgery of acute endocarditis with paravalvular
      abscess, however, supposedly carries an increased risk of early mortality and
      late morbidity. The following prospective study was carried out to determine
      whether a radical surgical approach together with aggressive postoperative
      antibiotic therapy could help to improve results. Between 1988 and 1995, 138
      patients were operated during the acute phase of infective endocarditis; in 102
      the aortic valve was involved. Among these, 44 had paravalvular abscesses at the
      time of surgery. The mean age of both groups was the same, but there was a higher
      rate of concomitant coronary artery disease, multiple valve involvement, advanced
      NYHA-class, and staphylococcal disease among the patients with abscesses. All
      interventions were carried out with cardiopulmonary bypass and cardioplegic
      arrest. The aortic valve was resected, abscesses were removed, and each part of
      potentially infected or necrotic tissue was resected as complete as possible,
      irrespective of the possibility to jeopardize the conduction system or to create
      large tissue defects. The aortic valve was replaced with a mechanical prosthesis
      in each case. The postoperative antibiotic regimen was specifically directed
      against the microorganisms isolated preoperatively; therapy was only modified, if
      signs of systemic infection did not disappear three days after surgery. The
      operative mortality was 10% among patients without an abscess and 11% in patients
      with a paravalvular abscess. Early recurrent endocarditis was recorded in two
      patients without and in only one patient with an abscess. Late recurrent
      endocarditis was noted in three patients; none of them had abscesses at the time
      of surgery. We conclude that the operative risk of acute endocarditis of the
      aortic valve with a paravalvular abscess does not have to be inevitably higher
      compared to cases without paravalvular involvement. To achieve these results, it
      is necessary to use a radical surgical approach and to adjust postoperative
      antibiotic therapy, if infectious signs do not disappear shortly after surgery.

PMID- 9610512
TI  - [Mechanical recanalization of venous thrombosis and pulmonary embolism with the
      Clotbuster thrombectomy system in a 12-year-old boy].
AB  - The treatment of patients with deep vein thrombosis and pulmonary embolism with
      contraindications for a thrombolytic therapy is a therapeutic challenge. We
      report on a 12 year old patient who was treated for large cell lymphoma according
      to NHL-BFM 95: Block AA protocol. During his therapy, he developed a thrombosis
      of his right femoral vein and pulmonary embolism affecting the left segments 4,
      5, 8, and 9. Because of cerebral metastasis a fibrinolytic therapy was
      contraindicated. Therefore, we performed a mechanical thrombectomy using the
      Amplatz thrombectomy device. The postinterventional scintigraphy showed a
      markedly improved pulmonary perfusion; dopplersonography 4 months
      postinterventionally showed a patent right femoral vein.

PMID- 9610513
TI  - [Echocardiography diagnosis of a partial anomalous pulmonary vein anastomosis in
      2 patients with Ullrich-Turner syndrome].
AB  - We report on 2 infants with Ullrich-Turner syndrome in whom partial anomalous
      pulmonary venous drainage was diagnosed noninvasively by color-coded Doppler
      sonography. Several patients with the combination of anomalous drainage of one or
      more pulmonary veins and Ullrich-Turner syndrome have been described in the
      literature. However, in the majority of those previously reported cases the
      diagnosis of partial anomalous pulmonary venous drainage was established by
      angiography during cardiac catheterization performed for confirmation of other
      cardiovascular malformations. Our patients show that partial anomalous pulmonary
      venous drainage can be diagnosed easily in neonates and young infants, as long as
      this anomaly is taken into consideration.

PMID- 9610515
TI  - [Myocardial infarct caused by dissection of the anterior interventricular ramus
      after blunt thoracic trauma--a case report].
AB  - A 23 year old man, having experienced sudden retrosternal pain, radiating to both
      hemithoraces, with dyspnea at rest was admitted to another hospital. The physical
      examination of heart and lung was unremarkable, but the patient showed discrete
      signs of a respiratory infection. Because of the young age and the history of a
      respiratory infection, the differential diagnosis perimyocarditis was favored and
      an appropriate treatment was begun. Five days later the patient was transferred
      to our center for cardiac catheterization and further treatment. After admission
      the patient was reported to be hit by a football shortly before the onset of
      symptoms. The electrocardiogram and chemical values showed the signs of
      myocardial damage with extensive myocardial necrosis. In the coronary
      arteriography a dissection of the proximal left anterior descending artery of a
      length of about 2 cm was seen; in the levocardiogram anterior akinesis was
      verified. Because of the already completed myocardial infarction, the short
      distance of the lesion to the left main coronary artery, and the restored flow in
      the left anterior descending, a non-invasive treatment was preferred. A control
      coronary arteriography five days later showed solely an irregularity of the
      vessel wall, the coronary dissection was not further demonstrable.

PMID- 9610514
TI  - [Loffler fibroblastic endocarditis in the thrombotic stages in isolated right
      ventricular tissue eosinophilia].
AB  - We report on a male, 31 year old, Turkish patient with an intracardiac mass in
      the right ventricle, reduction of performance and weight, as well as intermittent
      fever. No eosinophilia was documented in the peripheral blood; cardiac function
      was primarily normal. Besides the differential diagnosis of Loffer's endocarditis
      (endomyocardial fibrosis) an inflammatory disease and a malignant cardiac tumor
      were suggested. The diagnosis of Loffler's endocarditis could not be confirmed
      morphologically by echocardiography nor histologically by right ventricular
      biopsy. Operative removal of the mass lesion was necessary because of fast tumor
      progression, fulminant pulmonary embolism, and infiltration of the tricuspid
      valve. Only then, histologically Loffler's eosinophilic endocarditis of
      thrombotic stage was diagnosed. Antiphlogistic therapy with cortisone was
      initially performed. With a dose reduction after 6 months, a relapse of the
      thrombotic mass occurred. Therefore, continuous treatment with cortisone and
      azathioprine was induced followed by further tumor regression and further
      clinical stabilization since 8 months of treatment.

PMID- 9610516
TI  - [Induction of atrial fibrillation by adenosine in a patient with supraventricular
      tachycardia].
AB  - Adenosine is generally considered to be safe and effective in treatment of
      orthodromic circus movement tachycardia in patients with accessory pathways. We
      present a case with reproducible induction of atrial fibrillation after initial
      successful termination of orthodromic circus movement tachycardia using a left
      sided accessory pathway by adenosine. With the induction of atrial fibrillation
      sudden onset of preexcitation with subsequent rapid ventricular response was
      accompanied by moderate hemodynamic compromise. Before and after successful
      ablation of the accessory pathway, adenosine was not able to induce atrial
      fibrillation when applied during sinus rhythm. Adenosine induced atrial
      fibrillation is due to shortening of the atrial action potential duration and
      atrial refractoriness, whereas shortening of the antegrade refractory period in
      the accessory pathway leads to rapid conduction to the ventricles. Thus, care
      should be taken using adenosine in patients with orthodromic circus movement
      tachycardias and evidence of antegrade preexcitation during sinus rhythm.

PMID- 9610517
TI  - [Electrophysiologic studies of fecal incontinence in the woman].
AB  - The cause of urinary or fecal incontinence may be a complex one. A central or
      peripheral neurogenic lesion is frequently found to be accounting for the
      problem. The diagnosis should be specified by neurologic examinations and
      adequate neurophysiologic workup prior to any conservative or surgical treatment.
      Of particular expressiveness are, neurological history, both neurography of the
      pudendal nerve and electromyography of the external anal sphincter. Additional
      measures such as recording of the motor or sensory potentials, determination of
      reflex latencies and an electromyogram of other striated muscles of the pelvic
      floor may be taken as needed. Close co-operation of gynecologists, proctologists,
      and neurophysiologically trained neurologists will help to improve the prospects
      of treatment and avoid inappropriate therapeutic approaches.

PMID- 9610518
TI  - [Hugo Sellheim (1871-1936): Leipzig acknowledgement of gynecology].
AB  - In 1928 Hugo Sellheim, Professor and Chairman of gynaecology and obstetrics at
      the University of Leipzig (1926-1936), inaugurated the new Clinic of Gynaecology
      and Obstetrics. The opening ceremony found a critical public response. Although
      the new building had been drawn up by his predecessor Walter Stoeckel, Sellheim
      developed own ideas concerning the equipment of the institution. In Leipzig
      Sellheim is continued his scientific efforts with a story focus on female
      reproduction and its sociocultural impact during the period of the Weimar
      Republic.

PMID- 9610519
TI  - [Ambulatory versus inpatient laparoscopy: decision aids for choice of
      management].
AB  - 319 Patients are retrospectively competed, which underwent an inpatient or
      outpatient gynecological laparoscopy in 1992. Equality exists for martial status,
      education degree, nationality, anesthesiological risk and social structure.
      Outpatients are older, more rarely private assured, more often abdominal
      preoperated, have more children and live closer to the providing clinic. The
      satisfaction with the chosen medical care was outpatiently higher than
      inpatiently (97% vs 86%). In this context hesitation of security, quality of care
      and involvement at home are important. The inpatient group is characterized by
      patients with infertility, endometriosis and extrauterine gravidity, distance to
      employment and intensity of troubles have been important for the decision of
      medical providing. Outpatients were less anxious, sterilization and adhesions
      were main diagnoses. Here decisive factors for the choice of medical care have
      been care requiring relatives and financial aspects. By mean of these
      characteristics predictors are diverted for both kinds of care for being help to
      the advising doctor.

PMID- 9610520
TI  - [Determination of prostate-specific antigen (PSA) in cytosol of breast tumors and
      human endometrium--new diagnostic approaches].
AB  - Prostate specific antigen is a highly specific marker of prostatic tissue. Recent
      studies have shown, that it is present in several other human tissues, tumors and
      fluids. PSA has been identified as a serine protease and member of the kallikrein
      family of enzymes. In our study PSA concentration was measured in 97 cytosols of
      breast cancer tissues and 14 samples, prepared from human endometrium. Cytosols
      were analysed also for steroid hormone receptors, EGF-receptor, Cathepsin D and
      pS-2 protein. PSA was found in 84.5% of breast cancer tissues and in 12
      endometrium samples. High concentration of PSA were associated with high pS-2
      protein levels. No correlation was found between the concentration of steroid
      hormone receptors and PSA in our material. The results suggest, that PSA in
      cytosol of human breast cancer and endometrial tissues may be an additional new
      prognostic indicator.

PMID- 9610522
TI  - [What is the value of combined surgical-hormonal therapy of endometriosis
      management?].
AB  - Medical oestrogen suppressive therapy has to be considered as an important
      principle in the management of endometriosis. In the last years GnRHa became the
      "gold standard" as pre or postoperative measures before/after surgical
      intervention. We analyzed the data of 198 patients, most of them with recurrent
      endometriosis histologically confirmed during first-look laparoscopy. Patients
      were treated in a prospective, multicentre phase III study with the six months
      GnRHa leuprorelinacetate depot (LAD) followed by a second-look laparoscopy for
      precise assessment of therapeutic effects. In all stages of endometriosis a 35%
      reduction of the r-AFS-score compared to the baseline could be achieved due to
      surgical intervention during first-look laparoscopy with a further improvement of
      64% after GnRHa-therapy and surgery during second-look laparoscopy. Two subgroups
      of patients (24 vs. 45) could be analyzed according to the time of second-look
      laparoscopy (< or = 30 days vs. > or = 60 days after last injection) showing a
      comparable r-AFS-score reduction. Both, superficial lesions and deep infiltrating
      nodules, endometriomas, peritoneal implants and obliterated cul de sac could
      successfully be treated through the combined medical-surgical approach. Pre- or
      postoperative therapy with a GnRHa facilitates surgical excision of the implants,
      a subtle adhesiolysis and often complete removal of all visible lesions. In a
      high percentage of patients, including advanced stages of the disease, a
      preservation of ovarian tissue to ensure the childbearing potential could be
      achieved by minimal-invasive techniques. These results can be claimed as the
      prerequisites for long-term relief of endometriosis complaints and encouraging
      pregnancy rates in endometriosis related infertility. This confirms great
      clinical benefit of the combined medical-surgical approach for the treatment of
      this enigmatic disease.

PMID- 9610521
TI  - [Long-term outcome of incontinence and prolapse surgery with reference to
      multiple endogenous and exogenous risk factors for the female pelvic floor].
AB  - OBJECTIVE: The long-term results following different types of operations for
      urinary stress incontinence (minimum follow-up: 18 months) as well as multiple
      risk factors for the pelvic floor with regard to the results of surgery are
      reviewed in a retrospective study. STUDY DESIGN: Between 1980 and 1992 1283
      patients underwent surgery because of urinary stress incontinence with or at the
      University Women's' Hospital in Heidelberg. The data of 478 patients, 430 of
      those following primary surgery and 48 following recurrent surgery, were
      evaluated from questionnaires with regard to their risk profile and long-term
      results. RESULTS: 57% of patients following primary surgical therapy and 37%
      following recurrent surgery were cured for longer than 5 years or since the
      operation. A cure or improvement of the incontinence could be observed in 80%
      following primary and in 73% following recurrent surgery. Long-term results were
      significantly unfavorable, if the patient was exposed to one or several of the
      following risk factors: 1. Strain at work by carrying weights more than 5 kg 2.
      At least medium-hard housework, psychological tensions in the private sphere or
      idle women, who take a car for shopping 3. Double strain with at least medium
      high burden with house-work and physical strain at work CONCLUSION: Long-term
      results following primary urinary stress incontinence surgery are influenced by
      certain risk-factors.

PMID- 9610523
TI  - [Laparoscopy complications in previously operated patients].
AB  - Laparoscopic complications among previously operated patients and patients
      without prior surgical treatment are compared in a retrospective study during the
      period 1994-1996. Complications occurred in 2.15% of the 789 (33.2%) previously
      operated patients and in 1.0% of the 1,588 (66.8%) patients not previously
      operated. Apart from early conversion to laparotomy if the intraabdominal
      situation is difficult, approaches recommended to reduce the incidence of severe
      complications in the case of previously operated patients include, from among the
      risk-minimized laparoscopic techniques for the Veress needle and optical
      troicart, the use of open laparoscopy, access from the left mammillary line at
      the margin of the costal arch and minilaparoscopy. With regard to avoiding severe
      complications during laparoscopic surgery, attention is drawn to the advantages
      of conventional surgery (sharp preparation and stitching techniques) as opposed
      to coagulation techniques, the necessity of exposing the ureter if the situation
      is unclear and, besides taking all necessary precautions, close visual inspection
      at the end of laparoscopy.

PMID- 9610524
TI  - [Granulosa cell tumor: implantation metastasis to the abdominal wall].
AB  - We report on the rare localization of a metastasis in the abdominal wall of an
      ovarian Granulosa Cell Tumor, manifested as a haematoma in the abdominal wall
      nine years after the primary operation of the Granulosa Cell Tumor. The therapy
      consisted of a wide excision of the tumor, hysterectomy with a partial excision
      of the remaining ovary and resection of the omentum majus. Our case report
      illustrates the clinical problems of these kind of tumors.

PMID- 9610525
TI  - [Construction of a clinic web site].

PMID- 9610526
TI  - Summary of cardiovascular health conference.

PMID- 9610527
TI  - Inflammation in cardiovascular disease: cart, horse, or both?

PMID- 9610528
TI  - Remodeling of in-stent neointima, which became thinner and transparent over 3
      years: serial angiographic and angioscopic follow-up.
AB  - BACKGROUND: Recently, it has been reported that the luminal diameter shows phasic
      changes after stenting: the progression of luminal narrowing followed by its
      regression. To elucidate the mechanisms involved in the phasic changes in luminal
      diameter after stenting, we examined the changes in neointimal thickness and the
      appearance of neointima by a series of angiographic and angioscopic observations
      for 3 years after stent implantation. METHODS AND RESULTS: In 12 patients who
      received a Wiktor coronary stent, serial angiographic and angioscopic
      examinations were performed immediately, 2 to 4 weeks, 3 months, 6 months, and 3
      years after the stenting without repetition of angioplasty. Neointimal thickness
      was determined by angiography as the difference between stent and luminal
      diameters. The angioscopic appearance of neointima over the stent was classified
      as transparent or nontransparent according to the visibility of the majority of
      the stent. Neointimal thickness increased significantly at 3 months (0.75+/-0.32
      mm) without further changes at 6 months (0.74+/-0.32 mm). Thereafter, however, it
      decreased significantly over 3 years (0.51+/-0.26 mm). The angioscopic appearance
      was classified as transparent in 8 patients (100) immediately after stenting, 6
      patients (100%) at 2 to 4 weeks, 2 patients (17%) at 3 months, 2 patients (20%)
      at 6 months, and 7 patients (58%) at 3 years. CONCLUSIONS: The neointima became
      thick and nontransparent until 6 months and then became thin and transparent by 3
      years. We conclude that neointimal remodeling exists after stenting and plays a
      major role in the alteration of coronary luminal diameter after stenting.

PMID- 9610529
TI  - C-reactive protein adds to the predictive value of total and HDL cholesterol in
      determining risk of first myocardial infarction.
AB  - BACKGROUND: C-reactive protein (CRP) is a sensitive marker of inflammation, and
      elevated levels have been associated with future risk of myocardial infarction
      (MI). However, whether measurement of CRP adds to the predictive value of total
      cholesterol (TC) and HDL cholesterol (HDL-C) in determining risk is uncertain.
      METHODS AND RESULTS: Among 14916 apparently healthy men participating in the
      Physicians' Health Study, baseline levels of CRP, TC, and HDL-C were measured
      among 245 study subjects who subsequently developed a first MI (cases) and among
      372 subjects who remained free of cardiovascular disease during an average follow
      up period of 9 years (controls). In univariate analyses, high baseline levels of
      CRP, TC, and TC:HDL-C ratio were each associated with significantly increased
      risks of future MI (all P values <0.001). In multivariate analyses, models
      incorporating CRP and lipid parameters provided a significantly better method to
      predict risk than did models using lipids alone (all likelihood ratio test P
      values <0.003). For example, relative risks of future MI among those with high
      levels of both CRP and TC (RR=5.0, P=0.0001) were greater than the product of the
      individual risks associated with isolated elevations of either CRP (RR=1.5) or TC
      (RR=2.3). In stratified analyses, baseline CRP level was predictive of risk for
      those with low as well as high levels of TC and the TC:HDL-C ratio. These
      findings were virtually identical in analyses limited to nonsmokers and after
      control for other cardiovascular risk factors. CONCLUSIONS: In prospective data
      from a large cohort of apparently healthy men, baseline CRP level added to the
      predictive value of lipid parameters in determining risk of first MI.

PMID- 9610530
TI  - Passive smoking induces atherogenic changes in low-density lipoprotein.
AB  - BACKGROUND: According to the American Heart Association, passive smoking is an
      important risk factor for coronary heart disease (CHD), but the mechanisms
      underlying this association are not fully understood. We studied the acute effect
      of passive smoking on the factors that influence the development of CHD: the
      antioxidant defense of human serum, the extent of lipid peroxidation, and the
      accumulation of LDL cholesterol in cultured human macrophages, the precursors of
      foam cells in atherosclerotic lesions. METHODS AND RESULTS: Blood samples were
      collected during 2 ordinary working days from healthy, nonsmoking subjects (n=10)
      before and after (up to 5.5 hours) spending half an hour in a smoke-free area
      (day 1) or in a room for smokers (day 2). Passive smoking caused an acute
      decrease (1.5 hours after exposure) in serum ascorbic acid (P<.001) and in serum
      antioxidant defense (P<.001), a decreased capacity of LDL to resist oxidation
      (P<.01), and the appearance of increased amounts of lipid peroxidation end
      products in serum (P<.01). Finally, LDL isolated from subjects after passive
      smoking was taken up by cultured macrophages at an increased rate (P<.05).
      CONCLUSIONS: Exposure of nonsmoking subjects to secondhand smoke breaks down the
      serum antioxidant defense, leading to accelerated lipid peroxidation, LDL
      modification, and accumulation of LDL cholesterol in human macrophages. These
      data provide the pathophysiological background for the recent epidemiological
      evidence about the increased CHD risk among passive smokers.

PMID- 9610531
TI  - Transdermal nitroglycerin patch therapy improves left ventricular function and
      prevents remodeling after acute myocardial infarction: results of a multicenter
      prospective randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Nitrates are widely used in the treatment of angina in patients with
      acute myocardial infarction (AMI). Short-term administration prevents left
      ventricular (LV) dilation and infarct expansion. However, little information is
      available regarding their long-term effects on LV remodeling in patients
      surviving Q-wave AMI. METHODS AND RESULTS: This was a randomized, double-blind,
      placebo-controlled trial designed to investigate the long-term (6-month) efficacy
      of intermittent transdermal nitroglycerin (NTG) patches on LV remodeling in 291
      survivors of AMI. Patients meeting entry criteria had baseline gated radionuclide
      angiography (RNA) followed by randomization to placebo or active NTG patches
      delivering 0.4-, 0.8-, or 1.6-mg/h. RNA was repeated at 6 months and 6.5 days
      after withdrawal of double-blind medication. The primary study end point was the
      change in end-systolic volume index (ESVI). Both ESVI and end-diastolic volume
      index (EDVI) were significantly reduced with 0.4-mg/h NTG patches (-11.4 and 
      11.6 mL/m2, respectively, P<.03). This beneficial effect was observed primarily
      in patients with a baseline LV ejection fraction < or =40% (deltaESVI, -31 mL/m2;
      deltaEDVI, -33 mL/m2; both P<.05) and only at the 0.4-mg/h dose. After NTG patch
      withdrawal, ESVI significantly increased but did not reach pretreatment values.
      CONCLUSIONS: Transdermal NTG patches prevent LV dilation in patients surviving
      AMI. The beneficial effects are limited to patients with depressed LV function
      and only at the lowest (0.4-mg/h) dose. Continued administration is necessary to
      maintain efficacy. Whether these remodeling effects confer a clinical or survival
      advantage will need to be addressed in an adequately powered cardiac event trial.

PMID- 9610532
TI  - Endovascular beta-radiation to reduce restenosis after coronary balloon
      angioplasty: results of the beta energy restenosis trial (BERT).
AB  - BACKGROUND: In the porcine overstretch injury model of restenosis, endovascular
      beta-radiation reduces neointima formation. To determine whether this therapy
      could be applied to patients with coronary artery disease, a special device was
      developed to allow delivery of 12 encapsulated 90Sr/Y sources, measuring a total
      of 30 mm, to various sites within the coronary arterial tree. This study was
      designed to evaluate the feasibility of the delivery of 12, 14, or 16 Gy at 2 mm
      after balloon angioplasty of stenoses of native coronary vessels. METHODS AND
      RESULTS: Delivery of beta-radiation was attempted in 23 patients after successful
      balloon angioplasty. Source delivery was successful in 21 of the 23 patients
      (91%). There was no in-hospital or 30-day morbidity or mortality. Follow-up
      quantitative coronary arteriography in 20 patients demonstrated a late loss of
      0.05 mm, a late loss index of 4%, and a restenosis rate of 15%. The use of the
      beta-emitter 90Sr/Y significantly reduced treatment time and operator exposure
      compared with previous trials with the gamma-emitter 192Ir. CONCLUSIONS: In this
      study, the administration of endovascular beta-radiation after angioplasty was
      safe and feasible and substantially altered the postangioplasty late lumen loss,
      resulting in a lower-than-expected rate of restenosis. On the basis of these
      encouraging results, a multicenter, randomized trial with operators and patients
      blinded to treatment assignment is planned.

PMID- 9610533
TI  - Power-law relationship of heart rate variability as a predictor of mortality in
      the elderly.
AB  - BACKGROUND: The prognostic role of heart rate (HR) variability analyzed from 24
      hour ECG recordings in the general population is not well known. We studied
      whether analysis of 24-hour HR behavior is able to predict mortality in a random
      population of elderly subjects. METHODS AND RESULTS: A random sample of 347
      subjects of > or =65 years of age (mean, 73+/-6 years) underwent a comprehensive
      clinical evaluation, laboratory tests, and 24-hour ECG recordings and were
      subsequently followed up for 10 years. Various spectral and nonspectral measures
      of HR variability were analyzed from the baseline 24-hour ECG recordings. Risk
      factors for all-cause, cardiac, cerebrovascular, cancer, and other causes of
      death were assessed. By the end of 10-year follow-up, 184 subjects (53%) had died
      and 163 (47%) were still alive. Seventy-four subjects (21%) had died of cardiac
      disease, 37 of cancer (11%), 25 of cerebrovascular disease (7%), and 48 (14%) of
      various other causes. Among all analyzed variables, a steep slope of the power
      law regression line of HR variability (< -1.50) was the best univariate predictor
      of all-cause mortality (odds ratio, 7.9; 95% confidence interval [CI], 3.7 to
      17.0; P<.0001). After adjusting for age and sex and including all univariate
      predictors of mortality in the proportional hazards analysis, ie, measures of HR
      variability, history of heart disease, functional class, smoking, medication, and
      blood cholesterol and glucose concentrations, all-cause mortality was predicted
      only by the slope of HR variability (adjusted relative risk, 1.74; 95% CI, 1.42
      to 2.13; P<.0001) and a history of congestive heart failure (adjusted relative
      risk, 1.70; P=.0002). The slope of HR variability predicted both cardiac
      (adjusted relative risk, 2.05; P=.0002) and cerebrovascular death (adjusted
      relative risk, 2.84; P=.0001) but not cancer or other causes of death.
      CONCLUSIONS: Power-law relationship of 24-hour HR variability is a more powerful
      predictor of death than the traditional risk markers in elderly subjects. Altered
      long-term behavior of HR implies an increased risk of vascular causes of death
      rather than being a marker of any disease or frailty leading to death.

PMID- 9610534
TI  - Body weight reduction, sympathetic nerve traffic, and arterial baroreflex in
      obese normotensive humans.
AB  - BACKGROUND: Previous studies have shown that sympathetic cardiovascular outflow
      is increased in obese normotensive subjects and that this increase is associated
      with a baroreflex impairment. The purpose of this study was to determine whether
      these abnormalities are irreversible or can be favorably affected by body weight
      reduction. METHODS AND RESULTS: In 20 obese normotensive subjects (age, 31.3+/
      1.7 years; body mass index, 37.6+/-0.9 kg/m2, mean+/-SEM), we measured beat-to
      beat arterial blood pressure (Finapres technique), heart rate (ECG),
      postganglionic muscle sympathetic nerve activity (microneurography at a peroneal
      nerve), and venous plasma norepinephrine (high-performance liquid chromatography)
      at rest and during baroreceptor stimulation and deactivation induced by increases
      and reductions of blood pressure via stepwise intravenous infusions of
      phenylephrine and nitroprusside. Measurements were repeated in 10 subjects after
      a 16-week hypocaloric diet with normal sodium content (4600 to 5000 J and 210
      mmol NaCl/d) and in the remaining 10 subjects after a 16-week observation period
      without any reduction in the caloric intake. The hypocaloric diet significantly
      reduced body mass index, slightly reduced blood pressure, and caused a
      significant and marked decrease in both muscle sympathetic nerve activity (from
      50.0+/-5.1 to 32.9+/-4.6 bursts per 100 heart beats, P<.01) and plasma
      norepinephrine (from 356.2+/-43 to 258.4+/-29 pg/mL, P<.05). This was associated
      with a significant improvement in the sensitivity of the baroreceptor heart rate
      (+71.5 +/- 11%, P<.01) and muscle sympathetic nerve activity (+124.5 +/- 22%,
      P<.001) reflex. Total body glucose uptake also increased significantly (+60.8 +/-
      12.0%, P<.05), indicating an increase in insulin sensitivity. All variables
      remained unchanged in subjects not undergoing caloric restriction. CONCLUSIONS:
      In obese normotensive subjects, a reduction in body weight induced by a
      hypocaloric diet with normal sodium content exerts a marked reduction in
      sympathetic activity owing to central sympathoinhibition. This can be due to the
      consequences of an increased insulin sensitivity but also to a restoration of the
      baroreflex control of the cardiovascular system with weight loss.

PMID- 9610535
TI  - Reduced penetrance, variable expressivity, and genetic heterogeneity of familial
      atrial septal defects.
AB  - BACKGROUND: Secundum atrial septal defect (ASD) is a common congenital heart
      malformation that occurs as an isolated anomaly in 10% of individuals with
      congenital heart disease. Although some embryological pathways have been
      elucidated, the molecular etiologies of ASD are not fully understood. Most cases
      of ASD are isolated, but some individuals with ASD have a family history of this
      defect or other congenital heart malformations. METHODS AND RESULTS: Clinical
      evaluation of three families identified individuals with ASD in multiple
      generations. ASD was transmitted as an autosomal dominant trait in each family.
      ASD was the most common anomaly, but other heart defects occurred alone or in
      association with ASD in individuals from each kindred. Genome-wide linkage
      studies in one kindred localized a familial ASD disease gene to chromosome 5p
      (multipoint LOD score=3.6, theta=0.0). Assessment of 20 family members with the
      disease haplotype revealed that 9 had ASD, 8 were clinically unaffected, and 3
      had other cardiac defects (aortic stenosis, atrial septal aneurysm, and
      persistent left superior vena cava). Familial ASD did not map to chromosome 5p in
      two other families. CONCLUSIONS: Familial ASD is a genetically heterogeneous
      disorder; one disease gene maps to chromosome 5p. Recognition of the heritable
      basis of familial ASD is complicated by low disease penetrance and variable
      expressivity. Identification of ASD or other congenital heart defects in more
      than one family member should prompt clinical evaluation of all relatives.

PMID- 9610536
TI  - Gene for arrhythmogenic right ventricular cardiomyopathy with diffuse
      nonepidermolytic palmoplantar keratoderma and woolly hair (Naxos disease) maps to
      17q21.
AB  - BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heart
      muscle disease of unknown etiology that causes arrhythmias, heart failure, and
      sudden death. Diagnosis can be difficult, and this hampers investigation of its
      molecular basis. Forms of ARVC in which gene penetrance and disease expression
      are greater should facilitate genetic study. We undertook a clinical and genetic
      investigation of Naxos disease, originally described by Protonotarios in 1986.
      This disease constitutes the triad of ARVC, diffuse nonepidermolytic palmoplantar
      keratoderma, and woolly hair. METHODS AND RESULTS: We evaluated the population of
      Naxos, Greece, to identify probands, which was followed by family screening.
      Twenty-one affected persons from 9 families of 150 persons were identified.
      Linkage analysis was performed with microsatellite markers. The disease locus
      mapped to 17q21. A peak 2-point LOD score of 3.62 at theta=0.0 was found with a
      marker within intron 4 of the keratin 9 gene, a member of the type I (acidic)
      keratin family. A preserved homozygous disease haplotype was identified.
      Haplotype analysis delimited the disease interval. CONCLUSIONS: Hair and skin
      abnormalities were found to be reliable markers of subsequent heart disease. This
      suggests the presence of a single mutant gene with novel cardiac, skin, and hair
      function or two or more tightly linked disease genes. Recessive inheritance of
      Naxos disease and a founder effect were demonstrated. Identification of a fully
      informative genetic marker linked to the disease and uncommon in the background
      population may be of use as a test to identify disease gene carriers.

PMID- 9610537
TI  - Exacerbated transplant arteriosclerosis in inducible nitric oxide-deficient mice.
AB  - BACKGROUND: Inducible NO synthase (NOS2, or iNOS) is upregulated in grafts with
      transplant arteriosclerosis. However, the functional role of NOS2 in the
      pathogenesis of transplant arteriosclerosis remains unclear. NOS2 may regulate
      lesion development by modulating the early alloimmune response and/or late
      myointimal thickening. METHODS AND RESULTS: To determine whether NOS2-mediated
      pathways protect against or promote transplant arteriosclerosis, we used NOS2
      deficient mice as recipients in our vascularized chronic cardiac rejection model.
      The severity of vascular thickening in 55-day grafts placed into NOS2 -/-
      recipients (n=13) was compared with that in wild-type recipients (n=15). Computer
      assisted analysis of all elastin-stained vessels (n=283) showed significantly
      increased luminal occlusion (77.11+/-9.4% versus 40.8+/-13.6%, P<.0001) and
      intima/media ratios in allografts from NOS2 -/- recipients (1.9+/-1.3 versus
      0.4+/-0.3, P=.0002). To elucidate potential mechanisms, we studied NOS2 effects
      on T-cell differentiation (Th1/Th2) and neointimal smooth muscle cell
      accumulation. Normalized mRNA levels for Th1- (signal transducer and activator of
      transcription [STAT] 4, interleukin [IL]-2, interferon-gamma) and Th2- (STAT 6,
      IL-4, and IL-5) associated factors were comparable in both groups. In contrast,
      quantitative analysis of the alpha-actin-positive area showed a significant
      increase in the contribution of smooth muscle cells within the neointima in
      allografts from NOS2 -/- recipients (28.2+/-2.0%) compared with wild-type
      controls (13.2+/-2.3%; P<.0001). CONCLUSIONS: NOS2 plays a protective role in the
      development of transplant arteriosclerosis, suppressing neointimal smooth muscle
      cell accumulation.

PMID- 9610538
TI  - Nitric oxide-induced downregulation of Cdk2 activity and cyclin A gene
      transcription in vascular smooth muscle cells.
AB  - BACKGROUND: Nitric oxide (NO) inhibits vascular smooth muscle cell (VSMC)
      proliferation and neointima formation after balloon injury. However, the
      molecular mechanisms underlying NO-mediated growth arrest are poorly understood.
      In the present study, we examined the effects of the NO donors sodium
      nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP) on cell cycle
      activity in VSMCs. METHODS AND RESULTS: Stimulation of quiescent rat VSMCs with
      serum leads to an increase in cyclin-dependent kinase (cdk)2 kinase activity that
      correlates with a marked induction of cyclin A protein expression. The addition
      of SNP or SNAP to VSMC cultures at the time of serum stimulation abrogates the
      induction of cdk2 activity without suppressing protein levels of cdk2 or cyclin
      E. These NO donors block serum-stimulated upregulation of cyclin A mRNA and
      protein and repress the serum induction of cyclin A promoter activity in VSMCs.
      CONCLUSIONS: The addition of the nitric oxide donors SNP or SNAP to mitogen
      stimulated VSMCs prevents activation of cdk2, a key regulator of the G1 and S
      phases of the cell cycle. These NO donors do not affect the expression of cdk2
      protein but block the mitogen-induced expression of cyclin A, an activating
      subunit of cdk2. SNP and SNAP also repress the mitogen-stimulated activation of
      the cyclin A promoter. These data suggest that the antiproliferative effect of NO
      on VSMCs results, at least in part, from the repression of cyclin A gene
      transcription.

PMID- 9610539
TI  - Influence of phase duration of biphasic waveforms on defibrillation energy
      requirements with a 70-microF capacitance.
AB  - BACKGROUND: Phase duration of biphasic shocks may be an important determinant of
      defibrillation success. The purpose of this study was to investigate the effect
      of changing phase duration of biphasic pulses delivered by 70-microF capacitors
      on defibrillation energy requirements. This may be clinically relevant for the
      optimization of implantable cardioverter-defibrillator design and programming.
      METHODS AND RESULTS: Defibrillation thresholds (DFTs) were determined for 13
      waveforms in 13 pigs by application of a 70-microF capacitance and a
      transvenous/submuscular lead system. In part I, phase-1 duration varied,
      preserving a phase-1/phase-2 duration ratio of 60%/40%. The phase-1 durations
      were 1, 2, 3, 4, 5, and 6 ms. The DFT was lowest (22.9+/-7 J) for phase 1=3 ms
      compared with phase 1=1 ms (36.4+/-7.5 J), 2 ms (25+/-6.5 J), 4 ms (25+/-7.6 J),
      5 ms (30.7+/-7.3 J), or 6 ms (32.9+/-8.1 J) (P<.001). In part II, phase-1
      duration was 3 ms but phase-2 duration varied: 0.7, 1.3, 2, 2.7, 3.3, 4, and 6
      ms. Significant DFT minima were found at phase 2=2 ms (22.5+/-4.2 J) and phase
      2=4 ms (22.5+/-4.2 J) compared with phase 2=0.7 ms (31.7+/-9.3 J), phase 2=3.3 ms
      (26.7+/-6.1 J), or phase 2=6 ms (28.3+/-6.8 J) (P<.05). CONCLUSIONS: The strength
      duration curve of biphasic defibrillation shocks demonstrates a single optimum
      for phase-1 duration. In contrast, two optima with minimal energy requirements
      were found for phase-2 duration. Optimization of both phases of low-capacitance
      biphasic shocks may reduce energy requirements for defibrillation.

PMID- 9610540
TI  - Mechanical circulatory support and cardiac transplantation.

PMID- 9610541
TI  - Images in cardiovascular medicine. Fistula between left main, left anterior
      descending, and pulmonary arteries.

PMID- 9610542
TI  - Images in cardiovascular medicine. Amyloidosis with cardiac involvement.

PMID- 9610543
TI  - Electron beam CT and coronary calcium score.

PMID- 9610544
TI  - Alcohol therapy for hypertrophic cardiomyopathy: is it time to toast?

PMID- 9610545
TI  - Effect of warfarin on rate of restenosis after PTCA.

PMID- 9610546
TI  - Potassium channel-blocking actions of nifedipine: a cause for morbidity at high
      doses?

PMID- 9610547
TI  - The Hopkins rod-lens system and the Storz cold light illumination system.

PMID- 9610548
TI  - Laparoscopy for the evaluation and management of the nonpalpable testicle.
AB  - OBJECTIVE: To assess the usefulness of laparoscopy for the diagnosis and
      treatment of the nonpalpable testicle and to evaluate the results of laparoscopic
      orchidopexy. METHODS: We retrospectively reviewed the charts of 91 laparoscopies
      performed over a period of 4 years. We reviewed the following parameters:
      findings, complications, patency of the processus vaginalis, appearance of the
      cord structures, and the success of the different procedures performed for the
      intra-abdominal testicle. RESULTS: Fourteen patients had bilateral and 77
      unilateral nonpalpable testicles. The mean age of the patients was 39.5 +/- 50.8
      months. There were three laparoscopic complications (3.2%) one of which was a
      major bowel laceration. Laparoscopy defined the intra-abdominal anatomy
      accurately in 90 of the 91 cases Of the 26 intra-abdominal testicles above the
      ring, a one-stage laparoscopic orchidopexy was performed in five and a single
      stage standard orchidopexy in seven. All of these testicles remain viable and are
      in good position. Eight patients underwent a staged Fowler-Stephens orchidopexy
      with laparoscopic clipping of the spermatic vessels as the first stage. Of these,
      a second-stage open orchidopexy was performed in five and a laparoscopic
      orchidopexy in three. Testicular atrophy occurred in two of the patients who
      underwent the second-stage open orchidopexy. Three one-stage Fowler-Stephens
      orchidopexies were performed with testicular atrophy occurring in two of these
      testicles. Laparoscopic orchiectomy was performed on two patients. CONCLUSIONS:
      Laparoscopy is a valuable tool in the diagnosis and treatment of the nonpalpable
      testicle. Laparoscopic orchidopexy may decrease the rate of testicular atrophy
      since most of these can be performed laparoscopically in one stage, thus
      preserving the vascular supply.

PMID- 9610549
TI  - Ureteral valves in children.
AB  - OBJECTIVES: Congenital ureteral valves are a rare cause of ureteral obstruction
      in children, with only 42 cases having been reported in peer-reviewed literature.
      Eight additional cases of ureteral valves are herein reported. METHODS: We report
      on the diagnosis and management of eight children with ureteral obstruction
      secondary to a ureteral valve. RESULTS: Eight children with congenital ureteral
      valves were managed by ipsilateral ureteroureterostomy, ureteropyelostomy, or
      longitudinal ureterotomy with excision of valve leaflets. The obstruction was
      relieved in all. CONCLUSIONS: Ureteral valves should be included in the
      differential diagnosis of ureteral obstruction in children. Reconstruction is
      curative.

PMID- 9610550
TI  - Detrusorrhaphy for repair of unilateral vesicoureteral reflux: report of 76
      patients using a modified technique.
AB  - OBJECTIVE: To present our results for repair of unilateral vesicoureteral reflux
      in 76 children using a modified technique of detrusorrhaphy. METHODS: A
      retrospective chart review was performed for 76 children who underwent repair of
      unilateral vesicoureteral reflux by a modified technique of detrusorrhaphy. Of
      the 76 refluxing ureters, 12 were associated with historically refluxing
      contralateral ureters. In addition, 72/76 were grades II to IV; 4/76 grade V;
      three had a paraureteral diverticulum; four completely duplicated collecting
      systems; and two had associated ureteroceles. The surgical technique was modified
      to preserve both the obliterated umbilical artery and superior vesical pedicle
      and to minimize trigonal distortion through dissection lateral to the trigone in
      a direct path to the bladder neck. RESULTS: Seventy-five of 76 ureters were
      successfully repaired (99%). The remaining ureter showed initial improvement to
      grade I reflux and spontaneous resolution by 1 year. Obstruction did not occur.
      Three episodes of "new onset" contralateral vesicoureteral reflux were noted
      postoperatively. This represents a substantial decrease in incidence (3.9%) when
      compared with previously reported series (18%). CONCLUSION: Detrusorrhaphy is a
      reasonable treatment of unilateral vesicoureteral reflux with utility in the full
      range of anatomic associations. This approach is also associated with a lower
      incidence of new onset, contralateral reflux when compared with intravesical
      surgery.

PMID- 9610551
TI  - Buccal mucosal grafts for urethral reconstruction.
AB  - OBJECTIVES: Patients requiring urethral reconstruction but who have a paucity of
      usable genital tissue present a considerable technical challenge. Herein we
      report the experience of three centers in the use of buccal mucosa for urethral
      replacement. METHODS: From 1991 to 1996, 22 urethral reconstructions were
      completed using a graft of buccal mucosa. Eighteen of 22 patients had previously
      failed hypospadias repairs, while three had bulbar urethral stricture and one had
      penile carcinoma. Grafts were taken from either the inner cheek or the lower lip,
      and seven were used as a combined graft. Onlay grafts were used in 6 cases and
      tubularized grafts in 16 cases. RESULTS: Two patients developed complications at
      the donor site. Nine of 22 patients had complications of the urethroplasty-two
      had meatal stenosis, four developed a urethral fistula, and three developed
      urethral stricture. All complications have been managed successfully to date.
      CONCLUSIONS: Buccal mucosa is an excellent source of graft material for urethral
      replacement in complex urethroplasties. It is readily available, in abundant
      supply, and has physical properties beneficial to free graft survival.

PMID- 9610552
TI  - Abdominoscrotal hydrocele in infancy.
AB  - Abdominoscrotal hydrocele is an uncommon clinical entity. Fewer than 200 cases
      have been reported in the literature, only two of which described bilateral
      involvement. We present five cases of abdominoscrotal hydrocele occurring in
      infancy, three of which revealed bilateral disease. The first case represents the
      youngest patient ever reported with this condition and the first reported with
      secondary bilateral upper tract dilatation. The historical background,
      pathophysiology, diagnosis, and treatment are reviewed.

PMID- 9610553
TI  - Prenatal diagnosis of duplex system hydronephrosis: effect on renal salvage.
AB  - OBJECTIVES: To determine if prenatal identification of significant renal
      duplication anomalies affects the management of the patient or the clinical
      outcome. METHODS: This is a retrospective review of 79 consecutive children with
      severe hydronephrosis involving a duplex renal collecting system, identified by
      either prenatal ultrasound (asymptomatic), or symptoms, most often urinary tract
      infection, but also including abdominal mass, hematuria, or incontinence. An
      individualized combination of voiding cystourethrogram, ultrasound, intravenous
      urogram, and nuclear renal scan was used to assess anatomy and function. Ablation
      of the involved segment was carried out if no or extremely poor function was
      identified; a definitive reconstructive procedure was elected in the face of
      easily measureable function. Outcome was determined clinically and by repeat
      imaging. RESULTS: There was no difference in the rate of renal segment salvage
      between the prenatally and clinically diagnosed groups. Of the cases analyzed,
      20/79 were prenatally identified, of which 13/20 (65%) were reconstructed; 59/79
      were identified on clinical grounds, of which 34/59 (58%) were reconstructed. One
      patient in the prenatal salvage group underwent removal of the affected kidney 5
      years later. Another, in the clinical salvage group, underwent a successful
      secondary procedure for closure of a ureteral fistula. All others have shown
      improved function, drainage, or both in follow-up. No secondary procedures have
      been required for the ablation group to date. Follow-up ranges from 4 months to
      12 years. CONCLUSIONS: Prenatal identification of significant duplex system
      hydronephrosis does not improve the rate of renal segment salvage, as determined
      by standard radiographic means, compared to later identification on clinical
      grounds. The decision for reconstruction versus ablation in significant duplex
      system hydronephrosis can be made on the basis of function alone.

PMID- 9610555
TI  - Managed care and its impact on American urology.
AB  - America's health care is undergoing a revolution. A previous private, fee-for
      service, delivery system chiefly centered around hospital specialty care is
      rapidly being replaced by a commercialized system of managed care, controlled by
      businessmen whose prime motive is profit. Increasing emphasis of these managed
      care organizations is upon primary physicians who function as gatekeepers. While
      this new commercialized method of health care has been attended with reductions
      in the previous omnipresent health care inflation our country has experienced for
      the past several decades, its impact on quality of care and patient choice of
      physician remain a great concern. Especially vulnerable in this new system are
      our nation's academic centers, which, burdened with responsibility for education
      and research, are at a disadvantage in the competitive cost-based bidding for
      managed care contracts. Urology work force issues and the number of urologists in
      our nation remain another concern for urologists as they compete for access to
      patients in this new highly competitive environment. In a 1995 survey of a cohort
      of urologists in seven states, the respondents reported 35.8% of gross income
      came from managed care contracts, 86% reported the need for preservice approval
      for many diagnostic and therapeutic undertakings, 87% reported an inability to
      refer complex cases outside the Managed Care Organization (MCO) network, and 23%
      reported they were required to retain patients for treatment who they would have
      otherwise referred to a more qualified urologist. The majority of American
      urologists are reporting dropping gross revenues and increasing overhead in their
      dealings with managed care contracts. The advent of managed care is being
      attended with dropping gross revenues, increasing overhead costs and interference
      with the practice patterns of American urologists.

PMID- 9610554
TI  - Outcome of patients with vesicoureteral reflux after renal transplantation: the
      effect of pretransplantation surgery on posttransplant urinary tract infections.
AB  - OBJECTIVES: We evaluated the relation of vesicoureteral reflux, pretransplant
      nephrectomy, and prior ureteral reimplant with respect to posttransplant urinary
      tract infection and graft survival. METHODS: From 1984 to 1995, 820 renal
      transplants were performed. Thirty-six (4%) patients had documented
      vesicoureteral reflux. The patients were divided into three groups: Group I, N =
      10 (28%) underwent ureteral reimplantation prior to transplantation; Group II, N
      = 8 (22%) had bilateral nephrectomy prior to transplantation; and Group III, N =
      18 (50%) had persistent reflux at the time of transplantation. RESULTS: Graft
      survival at 3 years was 50% (18/36). Patient survival was 94% (34/36). The
      overall incidence of urinary tract infection was 56% (20/36). Complicated urinary
      tract infection was seen in 28% (10/36) and uncomplicated urinary tract infection
      in 47% (17/36) of the patients. The incidence of both complicated and
      uncomplicated urinary tract infection was lower in Group I. However, graft
      survival was lower in Group I patients. Overall graft survival was significantly
      lower in patients with vesicoureteral reflux compared with the rest of the group.
      CONCLUSIONS: The incidence of urinary tract infection did not appear to be
      altered significantly whether the patients had bilateral nephrectomy or
      persistent vesicoureteral reflux. However, those patients who had ureteral
      reimplantation had fewer episodes of infection. Nephrectomy prior to
      transplantation should be performed selectively.

PMID- 9610556
TI  - Managed care in the Northern California Kaiser Permanente health care system.
AB  - Kaiser Permanente in Northern California is a group model health maintenance
      organization (HMO) that contracts with The Permanente Medical Group, Inc. (TPMG)
      to provide care for health plan members. TPMG is the largest (for-profit) private
      group practice in the world, with 3600 physicians in Northern California,
      including 62 urologists, providing care to 2.5 million health plan members.
      Recent changes in health care financing and delivery mandate an HMO-physician
      relationship which addresses issues of cost, quality of care, and the needs of
      physicians.

PMID- 9610557
TI  - Relevance of the immune system in human urological malignancies: prospective for
      future clinical treatments.
AB  - The possible role of the immune system in resisting human malignancies has long
      been debated. Several recent findings from animal and human studies have
      restimulated interest in the immune surveillance hypothesis for tumor control.
      These findings have been complied from various disciplines including cytokine
      therapy, adoptive immunotherapy, and gene therapy. Following the initial
      euphoria, it is now clear that immunotherapy of selected cancer cases in the
      early stages of tumor development may make an important contribution to tumor
      control, particularly in dealing with minimal residual disease after tumor
      debulking. This review discusses some of these issues and proposes approaches
      that could pave the way for better selection of the patients best suited for
      immunotherapy. We would argue that therapies directed at the re-expression of
      major histocompatibility complex (MHC) class I antigens might improve outcomes in
      immune-therapy-based treatments.

PMID- 9610559
TI  - DNA cytometry and chromosome 9 aberrations by fluorescence in situ hybridization
      of irrigation specimens from bladder cancer patients.
AB  - OBJECTIVES: To determine the sensitivity and specificity of combining
      fluorescence in situ hybridization (FISH) measurement of chromosome 9 and DNA
      cytometry of bladder irrigation specimens in the detection of bladder cancer.
      METHODS: Bladder irrigation specimens were obtained from 37 normal control
      patients and 317 bladder cancer patients during cystoscopic examinations. Bladder
      cancer patients were sampled in the absence of observable tumor (256 specimens)
      and concurrently with tumor (204 specimens). Chromosome 9 copy number was
      determined on a cellular basis by FISH, and cellular DNA content was determined
      by Feulgen DNA staining and image cytometry. RESULTS: Sensitivity of chromosome 9
      FISH was 42% for all tumors and was not correlated to transitional cell carcinoma
      tumor grade, while the sensitivity of DNA cytometry was 55% and improved with
      increasing grade from 38% for grade 1 to 90% for grade 3 tumors. The results of
      FISH and DNA cytometry were combined, resulting in specificity of 92% and
      sensitivity of 69% for grade 1, 76% for grade 2, and 97% for grade 3 tumors.
      CONCLUSIONS: The lack of increase with grade in the percentage of positive
      specimens by FISH supports the hypothesis that chromosome 9 aberrations are
      critical events in bladder tumorigenesis for many patients. These data
      demonstrate the presence of cells in irrigation specimens with specific genomic
      lesions of chromosome 9 and DNA content. Combining FISH on chromosome 9 and DNA
      cytometry provides an increase in sensitivity to transitional cell carcinoma over
      either test alone.

PMID- 9610560
TI  - Voiding dysfunction in benign prostatic hyperplasia: trends, controversies and
      recent revelations. I. Symptoms and urodynamics.

PMID- 9610558
TI  - European Organization for Research and Treatment of Cancer (EORTC) prostate
      cancer trials, 1976-1996.
AB  - The Genito-Urinary Tract Cancer Cooperative Group (GU Group) is one of the 18
      European Organization for Research and Treatment of Cancer (EORTC) cooperative
      groups. It was established as a nonprofit organization in 1976 with the aim of
      conducting phase II and phase III clinical trials. Its membership includes
      urologists, oncologists, radiotherapists, and endocrinologists that work in close
      collaboration with its five data managers and one statistician in the EORTC Data
      Center. Eight subcommittees meet independently to plan and to monitor urological
      trials and to design programs on quality of life and quality control. In the past
      20 years, 3,500 prostate cancer patients have been recruited in 16 phase III
      trials in untreated and advanced disease and in seven phase II trials in hormone
      refractory, metastatic disease. This vast experience led the EORTC GU Group to be
      involved in the development of response and progression criteria, as well as the
      validation of prognostic factors, quality of life questionnaires, and basic
      expertise on the design and analysis of prostate cancer trials, including the
      meta-analysis of the trials with maximal androgen blockade. The conclusions drawn
      out of this large pool of experience show the complexity of the clinical research
      questions. Global collaboration and megatrials with the development of surrogate
      endpoints and the emphasis on quality of life may prove to be as important as the
      sacred overall survival endpoint.

PMID- 9610561
TI  - Voiding dysfunction in benign prostatic hyperplasia: trends, controversies and
      recent revelations. II. Pathology and pathophysiology.

PMID- 9610562
TI  - Current status and future directions in standardization of prostate-specific
      antigen immunoassay.

PMID- 9610563
TI  - Measurement of serum prostate-specific membrane antigen, a new prognostic marker
      for prostate cancer.
AB  - OBJECTIVES: To describe current results with Western blot assay for prostate
      specific membrane antigen (PSMA) using 7E11.C5 antibody and the development of an
      additional antibody measurement for PSMA by a new sandwich immunoassay. METHODS:
      A population of patients from a screening group, from a difficult diagnostic
      group, from a pre- and postoperative radical prostatectomy group, and from a
      group with metastatic disease followed for a serial period, provided the serum
      values for a prospective assessment of PSMA by Western blot assay. A new
      monoclonal antibody was sought, reacting to the C-terminal region of PSMA in
      order to develop a sandwich radioimmunoassay. RESULTS: PSMA values in screened
      patients correlate with the more advanced stage of the cancers determined. In
      postprostatectomy patients, the PSMA value corresponds more with preoperative
      values and with the values of those with a poor clinical course. In difficult
      diagnostic cases, the PSMA value is increased, specifically in hormone-refractory
      cases and particularly in those cases judged by other criteria, such as the
      National Prostatic Cancer Project, to be in clinical progression compared with
      those judged to be in clinical remission. The level of PSMA value appears to be
      independent of homogeneous tumor volume and to be more related to that of prior
      hormone treatment, or to where prostate cancer cells can be documented to be
      outside the prostate. A new monoclonal antibody, 3F5.4G6, reacts with the
      extracellular domain of PSMA near the C-terminal region. This is in contrast to
      the previously measured antibody 7E11.C5, which reacts with an N-terminal
      epitope. 3F5.4G6 recognizes the same PSMA protein as does 7E11.C5. The epitopes
      are essentially at opposite ends of the molecule. The 3F5.4G6 antibody reacts
      with the LNCaP line but not with DU145, or PC3. These two antibodies to PSMA are
      well suited for use in a new sandwich immunoassay. CONCLUSIONS: PSMA provides a
      prostatic cancer serum test by using Western blot, which suggests a clinical
      prognostic value not seen with other markers. New antibodies, such as 3F5.4G6,
      reacting with the extracellular domain of PSMA combined with 7E11.C5, appear to
      offer an opportunity for a new sandwich immunoassay.

PMID- 9610564
TI  - Percent free prostate-specific antigen: the next frontier in prostate-specific
      antigen testing.

PMID- 9610565
TI  - Characterization of the cell-specific expression of parathyroid hormone-related
      protein in normal and neoplastic prostate tissue.
AB  - OBJECTIVES: Parathyroid hormone-related protein (PTHrP) is a primary factor in
      the pathogenesis of malignancy-associated hypercalcemia. By alternative splicing,
      the human PTHrP gene can generate three different species of mRNA that encode
      three initial translational isoforms of 139, 173, and 141 amino acids. We
      recently reported that PTHrP was present in normal prostatic neuroendocrine cells
      and was overexpressed in prostate cancer tissue as demonstrated by
      immunostaining. This study was undertaken to further clarify the complex
      expression of PTHrP gene in normal prostate tissue and prostate cancer. METHODS:
      PTHrP mRNA in samples prepared from normal prostate tissue, prostate cancer, and
      three prostate cancer cell lines, PC3, LNCaP, and DU145 was assessed using
      Northern hybridization. Expressed PTHrP isoforms were deduced from differential
      reverse transcription-polymerase chain reaction (RT-PCR) assays with exon
      specific primers. Further localization of different species of PTHrP mRNA was
      performed using nonradioactive in situ hybridization with exon-specific probes on
      consecutive sections of normal and neoplastic prostate tissue. RESULTS: Northern
      hybridization showed that the PTHrP expression level was higher in prostate
      cancer than in normal prostate tissue. All three PTHrP isoforms could be detected
      in normal prostate tissues and prostate cancer with differential RT-PCR. Further
      analysis using in situ hybridization with exon-specific probes revealed that all
      three PTHrP isoforms were present in prostatic neuroendocrine cells and only
      PTHrP-1-139 isoform could be clearly detected in prostate cancer tissue. Two
      androgen-insensitive cell lines, PC3 and DU145, derived from a bone metastasis
      and a brain metastasis, respectively, expressed all three mRNA species encoding
      for the three isoforms, but DU145 cells expressed less than PC3 cells. Androgen
      sensitive LNCaP cells exhibited a low level of expression of mRNA species
      encoding for PTHrP-1-139 and PTHrP-1-173, and no expression of PTHrP1-141
      isoform. CONCLUSIONS: All three initial translational isoforms of PTHrP are
      produced by prostatic neuroendocrine cells. The mature products of PTHrP might
      exert their effects on other prostatic epithelial cells in a paracrine fashion
      and also participate in the homeostatic regulation of the ejaculate. In prostate
      cancer, differential expression of these three isoforms is evident and PTHrP-1
      139 isoform is more abundant than the other two forms. These findings are
      valuable for designing future research studies to further elucidate the
      biological functions of PTHrP in normal prostatic glands and prostate cancer.

PMID- 9610566
TI  - Neuroendocrine cells of the prostate and neuroendocrine differentiation in
      prostatic carcinoma: a review of morphologic aspects.
AB  - Neuroendocrine cells of the prostate are intraepithelial regulatory cells that
      secrete serotonin and a variety of peptide hormones. It is hypothesized that
      these cells regulate both growth and differentiation, as well as exocrine
      secretory activity through endocrine, paracrine, neurocrine, and lumenocrine
      mechanisms. Neuroendocrine differentiation in prostatic carcinoma occurs as pure
      neuroendocrine malignancies, such as small-cell carcinoma and carcinoid/carcinoid
      like tumors, as well as focal neuroendocrine differentiation in a more
      conventional prostatic adenocarcinoma. Neuroendocrine differentiation in
      prostatic carcinoma may have diagnostic and prognostic significance.

PMID- 9610567
TI  - The usefulness of prostate-specific antigen (PSA) density in patients with
      intermediate serum PSA level in a country with low incidence of prostate cancer.
AB  - OBJECTIVES: To evaluate if a calculated PSA density (PSAD) prior to biopsy could
      be useful to determine the need for prostate biopsies in patients with serum PSA
      levels of 4.1-20.0 ng/mL in a country with low incidence of prostate cancer
      (PCa). METHODS: A total of 185 consecutive patients aged 50-79 years who
      underwent prostate biopsies were evaluated by correlating the biopsy results with
      the results of digital rectal examination (DRE), transrectal ultrasonography
      (TRUS), serum PSA levels, and PSAD. Prostate volume was calculated from TRUS
      using prolate ellipse formula and PSAD was obtained by dividing serum PSA level
      by prostate volume. RESULTS: In this study population, 27 cases (14.6%) had
      positive biopsies. Of 158 cases with negative biopsies, 43 (23.2%) had
      histologically verified prostatic inflammation. The diagnostic value of DRE and
      TRUS was hampered by unsatisfactory sensitivity and specificity in
      differentiating patients with positive biopsies from those with negative
      biopsies. The use of PSAD alone as an indicator for biopsy was also limited by
      its low specificity. A PSAD cutoff value of 0.15 resulted in a sensitivity of
      100% and a specificity of only 12%. Prostatic inflammation was a confounding
      factor for the inadequate specificity of DRE, TRUS and PSAD. Combined use of DRE
      and PSAD provided the best information regarding the need for biopsies.
      Accordingly, if the 47 patients (25.4%) who presented with both a negative DRE
      and a PSAD < or = 0.20 were not biopsied, the rate of positive biopsy could have
      increased to 19.6% (27 of 138) without missing any cancer detection. CONCLUSIONS:
      It is concluded from this study that for patients with serum PSA levels of 4.1
      20.0 ng/mL, biopsies should only be recommended for those with abnormal DRE
      and/or PSAD >0.20.

PMID- 9610568
TI  - Lymphoceles after laparoscopic pelvic node dissection.
AB  - OBJECTIVE: Lymphocele formation has been infrequently reported as a complication
      of laparoscopic pelvic lymph node dissection (LPLND). We determined the incidence
      of clinical and subclinical lymphocele formation in patients undergoing
      transperitoneal LPLND. METHODS: Charts and radiological records of 111 patients
      undergoing transperitoneal LPLND at this institution between January 1991 and
      December 1995 were reviewed to determine the incidence of lymphocele formation.
      RESULTS: Of 111 patients undergoing LPLND, 12.6% had positive lymph nodes and
      received hormonal therapy. Radical retropubic (12) or perineal (28) prostatectomy
      was performed either simultaneously or within 2 weeks in 41% of the node-negative
      patients. Radiation therapy was the treatment modality in the remaining node
      negative patients (N = 57). Twenty-three patients undergoing radiation therapy
      had preplanning pelvic computed tomography (CT) scans 2 to 16 weeks (mean 8.2
      weeks) after LPLND. These were reviewed by a single radiologist to determine the
      presence of subclinical lymphoceles. Seven patients (30.4%) had lymphoceles of
      varying sizes (3 large and 4 small). Although most were identified on CT scans 4
      weeks after the procedure, two were identified on scans 12 and 16 weeks after the
      procedure (mean 6.5 weeks). None of these patients developed symptoms referable
      to or had treatment for the lymphocele during a 2 to 37 month follow-up (mean 20
      months). Only two patients (3.5%) undergoing LPLND as an isolated procedure had
      clinical evidence of lymphocele formation, both of which were subsequently
      confirmed with CT scans (1 large, 1 small). One was treated with CT-guided
      drainage and sclerosis and the other resolved spontaneously. CONCLUSION: The
      clinical incidence of lymphocele formation following LPLND remains relatively
      low. Only a portion of these patients requires intervention. Subclinical
      lymphoceles, as detected on follow-up CT scans, occur with a much greater
      frequency. These seldom become symptomatic requiring treatment. Rather, they
      appear to resolve spontaneously. Nevertheless, clinical suspicion should remain
      high in order to detect and properly treat symptomatic lymphoceles when they
      occur.

PMID- 9610569
TI  - Lymphoceles: diagnosis and management in urologic patients.

PMID- 9610570
TI  - Granins and prostate cancer.
AB  - OBJECTIVES: The importance of the expression of granin A (GRN-A, chromogranin-A)
      has become appreciated in the neuroendocrine differentiation of prostate cancer.
      We studied the expression of GRN-A in prostate cancer using serum immunoassay and
      tissue immunohistology procedures for this protein in order to define the
      clinical value of its measurements. METHODS: GRN-A production was measured by
      immunoassay in serum samples from patients with prostate cancer. Immunohistology
      procedures were used to assess GRN-A expression in paraffin-embedded prostate
      tissue samples. Serum and tumor findings were evaluated according to the
      patient's clinical status in studies by us and others. RESULTS: These studies
      demonstrated that GRN-A can serve as a prostate cancer serum and tumor marker
      with clinical value for both diagnosis and prognosis. Serum GRN-A was increased
      in early- and late-stage disease. Elevated serum GRN-A levels identified some
      patients with prostate cancer who did not have elevated serum prostate-specific
      antigen levels. In addition to their diagnostic value, increased serum GRN-A
      concentrations had prognostic value. CONCLUSIONS: Our own studies as well as
      those of others support the clinical potential of GRN-A as a marker for early,
      progressive, and recurrent prostate cancer. This demonstration of clinical
      utility notwithstanding, further studies are needed to clearly define the
      clinical value of GRN-A as a serum and tumor marker for this common cancer.

PMID- 9610571
TI  - From antibodies to sperm to antibodies in transplantation.
AB  - OBJECTIVES: a) To assess the use of "panning" procedures for the detection of
      antibodies to sperm. b) To develop and use human monoclonal antibodies for the
      analysis of human transplantation antigens. METHODS: "Panning" assays were
      developed. The procedures and their use in the analysis of mouse monoclonal
      antibodies to human sperm are described. B-lymphocytes from individuals
      sensitized by pregnancy, graft rejection, or blood transfusion were immortalized
      with Epstein-Barr virus (EBV). Selected sublines producing antibodies to human
      leukocyte series A (HLA) antigens were fused with mouse myeloma cells and
      selected clones of hybrid cells secreting monoclonal antibodies were selected.
      RESULTS: The results of panning assays correlated with those of agglutination
      assays, but not immunofluorescence or enzyme-linked immunosorbent assays (ELISA).
      Monospecific and cross-reactive human monoclonal antibodies to HLA antigens were
      produced. CONCLUSIONS: Panning assays can be used for the detection of antibodies
      to sperm and can be useful where target sperm are of poor motility. The assays
      may be more sensitive for antibodies to superficial antigens. Human monoclonal
      antibodies may be used for investigating the identity of, and responses to,
      transplantation antigens.

PMID- 9610572
TI  - The treatment of obstructive azoospermia in male infertility--past, present, and
      future.
AB  - Until recently, the primary treatment option for infertile men with obstructive
      azoospermia was the reconstruction of the male seminal tract when the causes of
      obstruction were reconstructable. For unreconstructable causes, such as
      congenital absence of the vas deferens, the primary treatment option involved
      implantation of an alloplastic artificial spermatocele for subsequent
      percutaneous retrieval of sperm. Retrieved sperm was then used for intrauterine
      insemination. The introduction of in vitro fertilization (IVF), performed
      together with microsurgical epididymal sperm aspiration (MESA), provided new
      frontiers for the treatment of unreconstructable obstructive azoospermic
      infertility in men. Against this background, the author reviewed the past and
      present status of the treatment of obstructive male infertility for the purpose
      of seeking a future course for the treatment of obstructive azoospermia. At the
      Andrology Clinic, 246 (26%) of 963 infertile males revealed azoospermia and 72
      (29%) of these 246 patients showed obstruction at the seminal tract, showing that
      7.5% of male infertility cases were caused by ductal obstruction. Microsurgical
      reconstruction of the seminal tract was performed, including vasovasostomy (29
      cases), epididymovasostomy (18 cases), and artificial spermatocele implantation
      (20 cases). Vasovasostomy resulted in an 81.3% patency rate and a 37.5% fertility
      rate. Epididymovasostomy showed a 71% patency rate and a 29% fertility rate. In
      contrast, artificial spermatocele implantation resulted in positive sperm present
      in the aspirated fluid in 33.3% of the patients; however, no pregnancy was
      achieved by artificial insemination using aspirated sperm. MESA together with
      assisted reproductive technology (ART) in 14 patients showed 79% ovum
      fertilization rates and a 35.7% clinical pregnancy rate. Thus, this new technique
      could open new frontiers for the future treatment of obstruction of the male
      seminal tract which cannot be reconstructed by vasovasostomy or
      vasoepididymostomy.

PMID- 9610573
TI  - Renal tubular dysfunction in patients with cystic disease of the kidneys.
AB  - OBJECTIVE: To define the renal tubular functional abnormalities in patients with
      cystic disease of the kidneys. METHODS: Patients with autosomal dominant
      polycystic kidney disease (ADPKD) (n = 4) and medullary sponge kidneys (MSK) (n =
      3) with normal glomerular filtration rate (GFR), determined by inulin clearance,
      and effective renal plasma flow (ERPF), measured by p-aminohippurate clearance,
      underwent measurement of proximal and distal tubular functions. Proximal tubular
      functions were determined by the maximum reabsorption of glucose (TmGlucose) and
      the maximum secretion of p-aminohippurate (TmPAH). Distal tubular functions were
      measured by the maximum urinary concentrating and diluting mechanisms, and the
      urinary acidification response to acid load. RESULTS: TmGlucose was low in both
      groups (209 +/- 25 mg/min/1.73 m2 in the ADPKD group and 110 +/- 28 mg/min/1.73
      m2 in the MSK, compared with 375 +/- 40 mg/min/1.73 m2 in healthy controls; P <
      0.05). Likewise, TmPAH was significantly diminished in patients with ADPKD (72 +/
      6 mg/min/1.73 m2) and MSK (63 +/- 5 mg/min/1.73 m2) when compared with healthy
      controls (89 +/- 4 mg/min/1.73 m2; P < 0.05). Urinary maximum concentration after
      fluid deprivation was impaired in both ADPKD and MSK patients, but the diluting
      mechanism was intact. Finally, the ability to excrete urinary ammonium and
      titratable acids following an oral acid load was inadequate in both the ADPKD and
      MSK groups. CONCLUSIONS: Proximal and distal tubular functions are impaired in
      patients with ADPKD and MSK when GFR and ERPF are normal, indicating tubular
      disruption by the cysts and the alteration of the tubulo-interstitial vascular
      relationship.

PMID- 9610574
TI  - Laparoscopic cryosurgery of the kidney in the porcine model: an acute
      histological study.
AB  - OBJECTIVES: To verify histologically whether cryosurgery of the kidney can be
      accomplished reproducibly without injuring adjacent structures, using a
      combination of ultrasound and laparoscopic guidance. MATERIALS AND METHODS: Six
      kidneys from three domestic female farm pigs were utilized in the study. Under
      general anesthesia and after obtaining pneumoperitoneum, the lower pole of the
      kidney was mobilized laparoscopically and the ureter and adjacent bowel were
      protected with saline-soaked gauze. Two 3.8 mm-cryoprobes were placed
      percutaneously into the lower pole and cryoablation was carried out under
      laparoscopic and ultrasound guidance using a double-freeze technique (10-minute
      freeze and 5-minute thaw cycles to a probe temperature of -185 degrees C to -196
      degrees C) in five kidneys (one control). The kidneys, adjacent ureter and bowel
      were harvested acutely, and macroscopic, histologic, and electron microscopic
      evaluation of all specimens was performed. RESULTS: Macroscopically, clear
      margins of cryodestruction corresponded with the ultrasound images of the
      iceball. In all five treated kidneys, reproducible cell death corresponding to
      visible margins of cryodestruction were verified histologically. Cell death was
      further corroborated by electron microscopy. Adjacent structures (ureter and
      bowel) were sectioned and no significant damage was noted. Blood pressure
      remained constant throughout the procedure. A crack in the renal parenchyma of
      one kidney was noted during the thaw phase; at harvest that animal was found to
      have an intraperitoneal hemorrhage. CONCLUSION: Combined laparoscopic and
      ultrasound-guided cryoablation of the lower pole of the kidney can be
      accomplished reproducibly in the porcine model without injury to adjacent
      structures.

PMID- 9610575
TI  - Intratesticular spermatocele.
AB  - High resolution ultrasound has increased our awareness of benign testicular cysts
      that appear to arise from the intratesticular sperm conduit system of the
      intratesticular ducts of the mediastinum and rete testis. The location of these
      benign cysts in the area of the mediastinum and rete testis and the absence of
      signs of a germ cell tumor may permit testicle preservation. These benign cysts
      may contain sperm. We present a case of a benign sperm-containing cyst with
      visible communication to the rete testis, designated an intratesticular
      spermatocele and managed with testicle preservation.

PMID- 9610576
TI  - Schistosomiasis in Saudi Arabia, Egypt, and Iraq.
AB  - The incidence of schistosomiasis, a parasitic infestation caused by trematodes,
      or flukes, has decreased significantly in Egypt and other Middle Eastern
      countries. The education of people in the countryside is a primary reason. The
      water supply in these countries is now good, and, in most areas, women no longer
      use the stagnant river tributaries for washing clothes. Medications, which can be
      used to prevent the infection or kill the parasite include praziquante and
      metrifonate.

PMID- 9610577
TI  - Role of radionuclide phallogram in therapeutic decision-making for erectile
      dysfunction.
AB  - OBJECTIVE: The purpose of this study is to evaluate the role of radionuclide
      phallograms in therapeutic decision-making for erectile dysfunction. METHOD:
      Forty-eight impotent men being considered for pharmacologically-induced penile
      erection therapy (PIPE) had radionuclide phallograms (RP) as part of their
      evaluation. RP were performed using 99mTc-labeled autologous red blood cells and
      provided a measurement of penile blood volume (PBV) change following the
      intracorporeal injection of 0.25 to 0.3 mL of a papaverine/phentolamine mixture.
      RESULTS: Thirty-eight patients showed a good response with a mean PBV increase
      2.6 times baseline (range 1.2 to 8.9). Ten patients had significantly lower PBV
      changes (P = 0.001) than the first group, with a mean PBV increase of 1.6 times
      baseline (range 1.1 to 2.4). These ten patients were dissatisfied with
      pharmacologically induced penile erection (PIPE) therapy after an unsuccessful
      treatment trial. CONCLUSION: We conclude that the RP can help to discriminate
      between patients who will benefit from PIPE therapy and those who will not.

PMID- 9610578
TI  - The use of amitriptyline in patients with urinary frequency and pain.
AB  - OBJECTIVE: To evaluate the usefulness of amitriptyline (AMI) in the treatment of
      patients with urinary frequency or genital, pelvic, or suprapubic pain syndromes.
      METHODS: Charts of 22 patients (12 male and 10 female) without interstitial
      cystitis and having vague nonspecific urinary and pelvic or genital complaints
      were reviewed. All were treated with AMI in doses ranging from 25 to 100 mg.
      RESULTS: Eleven patients became symptom-free, six showed significant improvement
      and five did not respond. Four of the five could not tolerate the medication.
      Fifteen patients attempted tapering off the medication after 6 months, and 11
      experienced an early return of symptoms. A therapeutic response was again seen
      with retreatment. CONCLUSIONS: AMI is therapeutically useful in vague voiding
      dysfunctions, especially in the presence of urinary frequency or genital, pelvic,
      or suprapubic pain. It is effective for the treatment of both men and women. The
      response is durable, but the dose of the medication must be maintained.

PMID- 9610579
TI  - Long-term effects of finasteride in patients with benign prostatic hyperplasia: a
      double-blind, placebo-controlled, multicenter study. PROWESS Study Group.
AB  - OBJECTIVES: To compare the long-term effects of finasteride (5 mg/day) and
      placebo in patients with moderate symptoms of benign prostatic hyperplasia (BPH).
      METHODS: Patients aged 50 to 75 years, with at least two urinary symptoms
      indicating moderate BPH, and an enlarged prostate, were followed in a 2-year
      double-blind, randomized, placebo-controlled multicenter study. The effects of
      finasteride versus placebo were assessed by total symptom score (modified
      Boyarsky), obstructive symptom score, maximal urinary flow rate, prostate volume,
      and urologic end points (acute urinary retention, BPH-related surgical
      intervention). RESULTS: Of the 3270 men enrolled, 3168 contributed data to the
      safety analysis, and 2902 to the efficacy evaluation. Significantly greater
      improvement with finasteride compared to placebo was observed at 12 and 24 months
      for total symptom score (mean -2.9 versus -1.9 at 12 months, P < or =0.001; -3.2
      versus -1.5 at 24 months, P < or =0.001), obstructive symptom score (mean -1.9
      versus -1.3 at 12 months, P < or =0.001; -2.1 versus -1.1 at 24 months, P < or
      =0.001), maximal urinary flow rate (mean +1.2 versus +0.6 mL/s at 12 months, P =
      0.010; +1.5 versus +0.7 mL/s at 24 months, P = 0.002), and prostate volume (mean 
      14.2 versus +5.4% at 12 months, P < or =0.01; -15.3 versus +8.9% at 24 months, P
      < or =0.001). Greater improvements in placebo-adjusted total symptom score
      occurred in men with large prostates than in men with small prostates (mean -2.4
      versus -1.1 at 12 months; -3.2 versus -1.3 at 24 months, placebo-adjusted data, P
      = 0.053). Fifteen of 1450 men (1.0%) in the finasteride group experienced an
      acute urinary retention event, compared with 37 of 1452 (2.5%) in the placebo
      group, and the corresponding figures for surgery were 51 of 1450 (3.5%) and 86 of
      1452 (5.9%), respectively. The hazard rate for occurrence, computed using the log
      rank statistic, decreased by 57% for acute urinary retention and by 40% for
      surgery accompanied by finasteride therapy compared to placebo. CONCLUSIONS:
      Finasteride causes long-term symptomatic improvement and reduces the risk of
      acute urinary retention or surgery. Men with enlarged prostates benefit most from
      finasteride treatment.

PMID- 9610580
TI  - Transurethral alprostadil as therapy for patients who withdrew from or failed
      prior intracavernous injection therapy.
AB  - OBJECTIVES: Patients experiencing erectile dysfunction who fail intracavernous
      injection (ICI) therapy are commonly believed to have exhausted pharmacologic
      options. We evaluated the efficacy and safety of transurethral alprostadil (MUSE)
      in patients experiencing erectile dysfunction who underwent prior ICI therapy
      (alprostadil, papaverine, phentolamine, or a combination of these). METHODS: Of
      the 1511 patients enrolled in a multicenter trial of transurethral alprostadil,
      452 (30%) reported prior ICI therapy and its effects. These patients tested up to
      four dose levels of transurethral alprostadil in the clinic, and those who
      achieved an erection satisfactory for intercourse were treated at home in a
      double-blind, placebo-controlled trial. RESULTS: Prior ICI therapy was reported
      to be "not effective" by 95 of 452 patients (21%), "sometimes effective" by 119
      of 452 (26%), and "effective" by 238 of 452 (53%). In patients reporting ICI
      therapy as "not effective," 58% achieved an erection sufficient for intercourse
      following transurethral alprostadil therapy in the clinic; 47% of these
      responsive patients reported successful sexual intercourse after transurethral
      alprostadil therapy during home treatment. For patients reporting ICI therapy as
      "sometimes effective" or "effective," 68% achieved an erection sufficient for
      intercourse following transurethral alprostadil therapy in the clinic setting and
      67% of these responsive patients reported successful intercourse following
      transurethral alprostadil therapy at home. Few adverse effects were encountered.
      The most common adverse effect was penile pain, which occurred with 7.8% of
      administrations. CONCLUSIONS: Transurethral alprostadil therapy is an effective
      therapeutic option for patients with erectile dysfunction and may even "rescue"
      some patients who have failed prior intracavernous injection therapy.

PMID- 9610581
TI  - Clinical significance of tumor angiogenesis in patients with localized renal cell
      carcinoma.
AB  - OBJECTIVES: To determine the relationship between angiogenesis and various
      histopathologic features as well as clinical outcome in patients with localized
      renal cell carcinoma (RCC). METHODS: Microvessel density was quantified by using
      immunocytochemical staining of endothelial cells for factor VIII-related antigen
      of 36 specimens taken from patients with pathologic Stage pT1 or pT2 RCC. All
      patients underwent radical nephrectomy and were followed for a mean time of 97.3
      months. RESULTS: No association was noted between microvessel count (MVC) and
      either cell type, architecture, or tumor size. Inverse correlation was noted
      between MVC and nuclear area (P = 0.006), nuclear elipticity (P = 0.016), nuclear
      roughness (P = 0.039), and histologic grade (P = 0.047). Patients having tumors
      with low MVC had significantly better survival rate compared with those with high
      MVC neoplasms (P = 0.0014, by Cox proportional hazards method). CONCLUSIONS:
      Despite lack of correlation with known predictors of survival, MVC provides
      independent prognostic information for patients with localized RCC.

PMID- 9610582
TI  - Results of a multicenter trial of the CapSure (Re/Stor) Continence shield on
      women with stress urinary incontinence.
AB  - OBJECTIVES: To prospectively study the impact of the CapSure (Re/Stor) Continence
      shield for the treatment of stress urinary incontinence. METHODS: One hundred
      women with pure stress urinary incontinence were enrolled in a 6-month study.
      Objective measures of urine loss included pad weight test (PdWt) and provocative
      stress test (PST). Subjective measures included incontinence diaries documenting
      the number of incontinence episodes per day (IEPD), quality of life
      questionnaires, and satisfaction surveys. Objective and subjective measures were
      performed prior to enrollment, during use of the CapSure shield, and after
      discontinuation of the device. RESULTS: During the 12-week device utilization
      period, PdWt measurements demonstrated a 96% reduction in urine loss by week 1
      and 97% by week 12. Eighty-two percent of subjects were completely dry by week
      12. PST demonstrated 100% reduction in urine loss at each visit, with 91% of
      subjects completely dry by week 12. IEPD also demonstrated a 91% reduction in
      incontinence episodes by week 12. Quality of life scores and patient satisfaction
      surveys demonstrated significant improvement. During the 6-week post device
      utilization period (PUP), subjects continued to demonstrate a reduction in urine
      loss compared to pre-enrollment data, despite discontinuation of use. PdWt
      measurements demonstrated a 73% and 79% reduction in urine loss at weeks 14 and
      18, respectively. Measurements of PST and IEPD demonstrated significant
      reductions in urine loss at weeks 14 and 18. A 1.5% prevalence of positive urine
      cultures was noted during device use. Bothersome vaginal or urethral irritation
      occurred in 12% of patients. Adverse events were few and required no therapeutic
      intervention. CONCLUSIONS: The CapSure shield is a safe and efficacious method of
      managing stress urinary incontinence in women.

PMID- 9610583
TI  - Pubovaginal sling using polypropylene mesh and Vesica bone anchors.
AB  - OBJECTIVES: To report preliminary results from a modified pubovaginal sling
      procedure using polypropylene mesh as the sling suspended by nonabsorbable
      sutures anchored to the pubic tubercle with Vesica bone anchors. METHODS: Thirty
      five women with type III stress urinary incontinence (SUI) (with or without
      associated urethral hypermobility) or type II SUI with additional risk factors
      such as obesity, chronic obstructive pulmonary disease, or failed prior
      incontinence-correcting procedures underwent this modified pubovaginal sling
      procedure. Postoperative voiding status was evaluated during office follow-up
      visits and telephone surveys. RESULTS: With a mean follow-up of 8.4 months (range
      2 to 18), 32 women (91.4%) were dry, 1 improved, and 2 remained incontinent. The
      pubovaginal sling procedure was the only operation performed in 46% of patients,
      with a mean operative time of 72 minutes, a mean estimated blood loss of 137 mL,
      and a mean hospital period of 2.3 days. Patients on whom concomitant gynecologic
      procedures were performed had a mean duration of surgery of 122 minutes, a mean
      estimated blood loss of 202 mL, and a mean hospitalization period of 2.9 days.
      Thirteen women had preoperative urgency that persisted in 31% of patients. De
      novo urgency developed in 3 patients. Seven women required prolonged suprapubic
      tube drainage but no patient remained in permanent retention. There has been no
      infection or erosion. CONCLUSIONS: Our experience with this modified pubovaginal
      sling procedure using polypropylene mesh and Vesica bone anchors showed excellent
      results with greater technical ease, minimal morbidity, and decreased
      hospitalization period when compared to a traditional pubovaginal sling performed
      in our hands. Additional follow-up will be needed to assess long-term efficacy.

PMID- 9610585
TI  - Correlation of ultrasound-estimated bladder weight with ultrasound appearance of
      the prostate and postvoid residual urine in men with lower urinary tract
      symptoms.
AB  - OBJECTIVES: To reveal the possible relationship of urodynamic tests and
      transrectal sonography (TRS) of the prostate with bladder hypertrophy as
      evaluated by ultrasound-estimated bladder weight (UEBW) in men with lower urinary
      tract symptoms. METHODS: In a total of 234 men aged 50 years or more with a
      normal prostate or benign prostatic hyperplasia (BPH) as determined by TRS, UEBW
      was correlated with age, the American Urological Association (AUA) symptom score,
      postvoid residual urine, maximum flow rate, and transrectal ultrasound planimetry
      such as prostatic volume and presumed circle area ratio (PCAR). RESULTS: In a
      simple regression analysis there was a statistically significant correlation
      between UEBW and the AUA symptom score (R = 0.282, P <0.0001), postvoid residual
      urine (R = 0.490, P <0.0001), prostatic volume (R = 0.358, P <0.0001), and PCAR
      (R = 0.468, P <0.0001). A multiple regression analysis demonstrated postvoid
      residual urine and PCAR to be significant independent determinants of UEBW. The
      frequency of abnormal UEBW (35.0 g or more) increased significantly with postvoid
      residual urine (P <0.0001) and PCAR (P <0.0001). CONCLUSIONS: Postvoid residual
      urine and PCAR were useful parameters for the evaluation of the severity of BPH
      in terms of bladder hypertrophy probably due to infravesical obstruction.

PMID- 9610584
TI  - Postprostatectomy urinary incontinence: a comparison of the cost of conservative
      versus surgical management.
AB  - OBJECTIVES: Post-radical prostatectomy stress incontinence occurs in up to 20% of
      patients. Postprostatectomy incontinence is initially treated with undergarments,
      pads, or drip collectors. Patients with persistent leakage are often treated with
      a transurethral bulking agent (Contigen) or placement of an artificial
      genitourinary sphincter (AGUS). We have compared the direct costs of each
      treatment at our institution over 10 years. METHODS: The Mayo Clinic estimating
      office provided the Medicare and non-Medicare charges for patients receiving both
      collagen injection (outpatient) and AGUS placement (2-day hospitalization) during
      August 1995. The Mayo Store provided the current price of all undergarments,
      pads, and drip collectors carried. Two local grocery stores provided the cost of
      Depends undergarments. RESULTS: The following items were the least expensive
      carried at the Mayo Clinic Store: Entrust undergarments, Active Style pads, and
      Conveen drip collectors at $0.99, $0.52, $1.05 each, respectively. The average
      cost of Depends undergarments was $0.52 each. The cost of wearing 5 of the least
      expensive undergarments or pads per day for 10 years is $9497. The average
      estimated Medicare and non-Medicare cost for outpatient (general anesthesia)
      collagen injection is $4300 and $5625, respectively. The average Medicare and non
      Medicare cost for AGUS placement is $15,400 and $20,300, respectively. Factoring
      in our current 22.4% reoperation rate, the average per patient Medicare and non
      Medicare cost for AGUS placement is $18,850 and $24,847, respectively.
      CONCLUSIONS: The cost of the AGUS placement compares favorably with the cost of
      transurethral collagen injection (under general anesthesia) in patients requiring
      several (more than three) collagen injection treatments or requiring the
      continued use of undergarments after collagen injection. Whereas the cost of
      transurethral collagen injection, when effective, compares favorably with
      conservative treatment, AGUS placement is significantly more expensive than
      conservative management for almost all patients except the exceedingly rare
      patient wearing more than 9 undergarments or pads per day. When the psychosocial
      benefit of urinary continence is considered, however, transurethral injection of
      collagen or AGUS placement often becomes the preferred treatment.

PMID- 9610586
TI  - A high-efficiency microwave thermoablation system for the treatment of benign
      prostatic hyperplasia: results of a randomized, sham-controlled, prospective,
      double-blind, multicenter clinical trial.
AB  - OBJECTIVES: To determine the effectiveness, safety, and impact on patient quality
      of life (QOL) of a novel transurethral microwave thermoablation system for the
      treatment of benign prostatic hyperplasia (BPH). METHODS: A total of 169 patients
      with BPH were randomized to undergo a 1-hour microwave (n = 125) or sham (n = 44)
      procedure using the Urologix Targis thermoablation system on an outpatient basis,
      without general or regional anesthesia. Symptoms, flow rates, and QOL scores were
      determined before the study procedure and periodically thereafter up to 6 months.
      RESULTS: Mean American Urological Association (AUA) score in the microwave group
      diminished 50% (P <0.0005) by the 6-month evaluation (10.5, 95% confidence
      interval [CI] 9.2 to 11.8) compared with baseline values (20.8, 95% CI 19.8 to
      21.9). The sham group also exhibited lower postprocedural AUA scores; however,
      the magnitude of the postprocedural decline in AUA score in the microwave group
      was significantly greater (P <0.01) than that in the sham group. Half the
      microwave group had an AUA score of less than 9 by 6 months, and the decrease in
      symptoms was similar among patients with initially moderate versus initially
      severe symptoms. Mean peak urinary flow rate (Qmax) in the microwave group
      increased 51% (P <0.0005) by 6 months to 11.8 mL/s (95% CI 10.7 to 13.0) versus a
      pretreatment value of 7.8 mL/s (95% CI 7.4 to 8.2). The magnitude of the
      postprocedural increase in Qmax was significantly greater in the microwave than
      the sham group (P <0.05). In nearly half the microwave group (47%), Qmax
      increased 50% or more by 6 months compared with 24% of the sham group. Microwave
      treatment resulted in a significantly greater (P <0.05) positive impact on
      patient QOL than did the sham procedure. By 6 months, the QOL score in microwave
      treated patients (2.2, 95% CI 1.9 to 2.4) averaged 48% lower (P <0.0005) than
      that at baseline (4.2, 95% CI 4.0 to 4.4). Significantly greater durability of
      treatment effects was also evident with microwave than with sham treatment, as
      judged by the higher proportion of microwave-treated patients (98.4%) requiring
      no further treatment during the 6-month study period versus 83.3% of sham control
      patients (P <0.0005). Microwave treatment was well tolerated, and complications
      were generally minor, readily manageable, and transitory. CONCLUSIONS: The
      microwave thermoablation system proved to be an effective and safe treatment
      modality for BPH, with a positive impact on patient QOL.

PMID- 9610587
TI  - Association of benign prostatic hyperplasia with male pattern baldness.
AB  - OBJECTIVES: Both benign prostatic hyperplasia (BPH) and male pattern baldness
      (androgenic alopecia) share the pathogenesis of an androgen-dependent disorder
      and afflict a large population of elderly men with chronobiologic progress.
      However, it is unclear whether these diseases are related epidemiologically. We
      evaluated the association of frequency and severity of male pattern baldness
      between patients with BPH and a control group. METHODS: A total of 225 patients
      with BPH (mean age 69.3 +/- 6.5 years) and 1 60 controls (mean age 68.5 +/- 6.4
      years), all over 60 years of age, were included in this study. The estimation of
      baldness severity was based on Norwood's classification (grade I to VII). The
      International Prostate Symptom Score (IPSS) and genetic tendency for baldness
      were also evaluated. The difference between IPSS and grade of baldness between
      the two groups was analyzed by the Mann-Whitney test and the frequency of
      inherited baldness was compared by the chi-square test. Correlation between
      severity of baldness and IPSS in each group was estimated by Spearman's rank
      correlation method. RESULTS: The patients with BPH had an apparently higher grade
      of male pattern baldness in comparison with that of controls (median value of
      grade IV versus III, P <0.001). The proportion of men with male pattern baldness
      of grade IV or higher in the BPH group was significantly larger than that of
      controls (53.8% versus 36.9%, P <0.01). There was a greater frequency of
      inherited baldness in the BPH group than in the controls (31.6% versus 12.5%, P
      <0.001). No significant correlation was noted between baldness severity and IPSS
      in either group. CONCLUSIONS: This study demonstrates a strong association of BPH
      with male pattern baldness.

PMID- 9610588
TI  - Diagnosis of "suspicious for malignancy" in prostate biopsies: predictive value
      for cancer.
AB  - OBJECTIVES: Prostate needle biopsies occasionally contain an atypical small
      acinar proliferation (ASAP) that is suspicious for but not diagnostic of
      malignancy. The predictive value of ASAP for cancer has not been studied in a
      large series. METHODS: To determine the reproducibility and clinical significance
      of ASAP in a large urologic reference laboratory, we retrospectively studied 295
      patients with ASAP diagnosed from 1991 to 1995. Each patient had at least one
      follow-up biopsy. Mean patient age was 68.0 years (range 40 to 89). Numerous
      clinical and histologic features were assessed to determine their predictive
      value for malignancy on subsequent biopsy. RESULTS: Adenocarcinoma was identified
      on follow-up biopsy in 125 patients (42%), with a median follow-up of 5.7 months
      (range 0.1 to 43). Gleason score varied from 4 to 9 (mean 6.2). Cumulative
      detection of 125 cancers was 90% after second biopsy and 99% after third biopsy.
      Serum prostate-specific antigen, digital rectal examination result, and patient
      age were not predictive of cancer on follow-up biopsy. Likewise, the number of
      biopsy cores and histologic findings including number of acini per focus of ASAP,
      number of foci of ASAP, degree of nuclear and nucleolar enlargement, and presence
      of luminal pink granular secretions, mucin, or crystalloids were not predictive
      of cancer. Stratifying our level of suspicion into three categories (favor
      benign, uncertain, and favor carcinoma) did not differentially predict subsequent
      cancer (44%, 44%, and 41% of patients, respectively; P = 0.86) nor the percentage
      of tissue involved by cancer. No clinical or pathologic feature affected the
      likelihood of subsequent cancer. In 39% of patients, cancer was only
      contralateral to or in a different sextant site from the initial ASAP site.
      CONCLUSIONS: The high predictive value of ASAP for subsequent adenocarcinoma
      warrants repeat biopsy. Sampling should include multiple sites in the prostate.

PMID- 9610589
TI  - Ability of sextant biopsies to predict radical prostatectomy stage.
AB  - OBJECTIVES: There are few studies evaluating multiple variables on sextant
      biopsies with the intent to predict stage in radical prostatectomy specimens.
      METHODS: We studied 113 sextant biopsies with corresponding totally submitted
      radical prostatectomy specimens. Variables evaluated on sextant biopsies included
      total length and percent of cancer; maximum length and percent of cancer on one
      core; location (apex, mid, base); bilaterality; Gleason grade; number of cores
      involved; serum prostate-specific antigen (PSA) level; and serum PSA density
      (PSAD). Radical prostatectomy stage was classified as organ versus non-organ
      confined. RESULTS: The following variables individually correlated with radical
      prostatectomy stage: total cancer measured in millimeters (P <0.0001) or percent
      (P <0.0005); biopsy Gleason score (P <0.0001); number of involved cores (P
      <0.0001); maximum cancer on one core measured in millimeters (P = 0.0001);
      maximum percent of cancer on one core (P = 0.01); bilaterality (P = 0.01); PSA
      level (P = 0.03), and PSAD (P = 0.001). The most predictive sets of two variables
      that correlated with stage included high Gleason score (P <0.0001) combined with
      numbers of cores involved (P = 0.002). When biopsies had Gleason scores of 6 or
      less, two or fewer positive cores, and serum PSA of 0 to 4 ng/mL, 89% were organ
      confined. When biopsies had Gleason scores of 6 or less with two unilaterally
      positive cores, 87% were organ confined. In biopsies with Gleason scores of 7 or
      more and more than one positive core, only 10% were organ confined. CONCLUSIONS:
      The most important predictors of stage by sextant needle biopsy evaluation are
      numbers of cores involved with carcinoma and high Gleason score. Bilaterality and
      serum PSA values improved prediction in two small subgroups. In 37% of our
      population we were able to predict with a greater than 87% probability the organ
      confined versus non-organ-confined status.

PMID- 9610590
TI  - Initial dissection of the lateral fascia reduces the positive margin rate in
      radical prostatectomy.
AB  - OBJECTIVES: Positive margins predict an adverse outcome after radical retropubic
      prostatectomy (RRP). The effect of initial incision of the lateral pelvic fascia
      prior to urethral transection on positive margins rates is assessed. METHODS: The
      rate of positive margins in 350 consecutive RRPs is compared in two groups
      without hormonal pretreatment. In group 1 (n = 198), RRP was performed in
      standard fashion with apical dissection and urethral transection preceding
      dissection of the lateral pelvic fascia and mobilization of the prostate from the
      anterior rectal surface. In group 2 (n = 1 52), the initial step consisted of
      incision of the lateral pelvic fascia along the perirectal surface with prostatic
      mobilization off the rectum prior to urethral transection. The bladder neck and
      seminal vesicle dissection was identical in both groups. Specimens were step
      sectioned for histologic analysis. Differences in rates of positive margins were
      analyzed by Fisher's exact test and logistic regression. RESULTS: The rate of
      positive margins was reduced from 37.4% in group 1 to 15.8% in group 2. In the
      logistic regression model, surgical technique, Gleason sum, serum prostate
      specific antigen (PSA), and the presence of extracapsular extension were
      independent predictors of margin status, with group 1 being more than twice as
      likely to have positive margins than group 2 (P = 0.0076; odds ratio 2.198; 95%
      confidence interval 1.23 to 3.92). The rate of positive margins was reduced from
      45.5% in group 1 to 16.7% in group 2 (P = 0.0046) for non-nerve-sparing RRP and
      from 33.3% to 15.5% (P = 0.0012) for nerve-sparing RRP. There were no differences
      in functional outcomes between groups and no rectal injuries in group 2.
      CONCLUSIONS: Initial dissection of the lateral pelvic fascia during RRP results
      in a lower rate of positive margins independent of tumor grade, clinical stage,
      extracapsular extension, and preoperative PSA level.

PMID- 9610591
TI  - Idiopathic thromboembolism as the presenting sign of occult prostate cancer.
AB  - OBJECTIVES: Idiopathic thromboembolism has been associated with occult neoplasia;
      however, very limited information exists regarding a man's risk of occult
      prostate cancer after an idiopathic thromboembolic event. METHODS: We performed a
      case-control study of 209 consecutive men diagnosed with prostate cancer over a 3
      year period, with 350 men diagnosed with benign prostatic hyperplasia (BPH)
      serving as control subjects. RESULTS: Men with idiopathic thromboembolism had a
      fivefold increased risk of prostate cancer compared with the BPH control group
      (risk ratio = 5.0, P = 0.002). The prostate-specific antigen (PSA) progression
      free survival was not adversely affected after an idiopathic thromboembolic
      event. CONCLUSIONS: Our data suggest that men with idiopathic thromboembolism are
      at an increased risk for being diagnosed with prostate cancer. In men with
      idiopathic thromboembolism, attempts to diagnose prostate cancer, including
      digital rectal examination and serum PSA, warrant consideration.

PMID- 9610592
TI  - Stage T3 prostate cancer: a nonrandomized comparison between definitive
      irradiation and induction hormonal manipulation plus prostatectomy.
AB  - OBJECTIVES: At our institution, a Phase II trial using androgen suppression
      followed by surgery was completed for men with Stage T3 disease and negative
      laparoscopic nodal dissection. We recently reported the unfavorable biochemical
      outcome of that experience. Because that analysis did not include a control group
      of irradiated patients, the current project was undertaken to compare that Phase
      II experience with clinical Stage T3 patients treated at our institution with
      definitive irradiation during an overlapping period of time. METHODS: The Phase
      II trial included 21 patients with T3 tumors and negative laparoscopic nodal
      dissections treated by 4 months of neoadjuvant hormonal treatment (leuprolide +/-
      flutamide) prior to radical prostatectomy. Patients who declined to participate
      in the study or those judged ineligible by virtue of poor surgical risk were
      treated with definitive irradiation (n = 29). Although the radiation portals were
      shaped with multileaf collimation, no attempt was made to design "conformal
      fields." The median dose was 68 Gy (range 66 to 72) delivered in conventional
      fractionation. Biochemical failure after prostatectomy was defined as prostate
      specific antigen (PSA) levels exceeding 0.2 ng/mL. Biochemical failure after
      irradiation was defined as a rise in absolute level of PSA greater than 1.5
      ng/mL, or two consecutive elevations of PSA on sequential measurements, even if
      the absolute level was less than 1.5 ng/mL. RESULTS: In univariate comparison,
      the freedom from biochemical relapse rate at 3 years was 41% for irradiated
      patients and 23% for those treated by hormones combined with surgery (P <0.05).
      In a multivariate regression model controlling for the prognostic factors of
      baseline PSA, age, clinical substage, Gleason score, and treatment modality
      (induction androgen suppression + prostatectomy versus radiotherapy), only low
      baseline PSA independently predicted improved freedom from biochemical recurrence
      (P = 0.04). CONCLUSIONS: The combination of induction hormonal treatment followed
      by radical prostatectomy offered no advantage over irradiation alone in this
      single institutional experience. Notwithstanding, the majority of men treated by
      definitive radiotherapy manifested biochemical failure. More innovative
      strategies such as conformal irradiation (either alone or combined with androgen
      ablation) and radiation dose escalation should be pursued to optimize outcome for
      this unfavorable group of patients.

PMID- 9610593
TI  - Predictors for maximal outcome in patients undergoing salvage surgery for radio
      recurrent prostate cancer.
AB  - OBJECTIVES: To determine preradiation and preoperative clinical staging and
      postoperative pathologic factors that can predict disease-free survival in
      patients undergoing salvage surgery for radio-recurrent prostate cancer. METHODS:
      A retrospective review was performed on 40 patients who underwent salvage surgery
      for radio-recurrent prostate cancer. Preradiation and preoperative clinical
      staging factors, as well as pathologic stage were analyzed as predictors of
      disease-free survival. Biochemical failure was defined as a persistent serum
      prostate-specific antigen (PSA) elevation greater than 0.4 ng/mL. RESULTS: As a
      group, salvage surgery provided excellent clinical disease control in 35 of 40
      patients (87.5%). Overall, 18 of 38 (47.4%) patients analyzed had no evidence of
      biochemical progression. Preradiation clinical stage and pathologically organ
      confined disease were statistically significant predictors of disease-free
      survival (P = 0.03 and P = 0.02, respectively). Seminal vesicle invasion and
      positive lymph nodes were the worst pathologic prognostic factors. Preoperative
      clinical T1c disease approached statistical significance in predicting
      pathologically organ-confined disease and disease-free survival (P = 0.08 and P =
      0.07, respectively). CONCLUSIONS: Ideal candidates for salvage surgery should
      have preradiation and preoperative clinically organ-confined disease. All
      patients with pathologically organ-confined disease following salvage
      prostatectomy were disease free at a mean follow-up of 36.1 months. Salvage
      surgery, although technically feasible, should not be widely advocated as an
      effective curative treatment in patients with locally advanced disease at the
      time of diagnosis.

PMID- 9610594
TI  - Outpatient ultrasound-guided palladium 103 brachytherapy for localized
      adenocarcinoma of the prostate: a preliminary report of 434 patients.
AB  - OBJECTIVES: To assess the effectiveness of palladium 103 (Pd-103) brachytherapy
      in Stage T1 and T2 adenocarcinoma of the prostate. METHODS: Charts of 474
      patients treated between 1991 and 1996 with transperineal real-time ultrasound
      guided Pd-103 implants were reviewed to assess post-treatment prostate-specific
      antigen (PSA) levels and follow-up biopsy results. Of 474 patients, 434 had
      sufficient data for this report. The implant technique used allows precise
      placement of seeds and accurate dose delivery of the entire prostate.
      Preoperative neoadjuvant leuprolide (Lupron) and flutamide (Eulexin) were given
      selectively to reduce prostate size greater than 50 cc and for Gleason grade
      lesions greater than 7. RESULTS: Of 434 patients, successful cancer control was
      demonstrated in 81% of patients by a decrease in PSA levels to less than 1.5
      ng/mL at 1 year. Biopsies were negative in 88% of patients 1 year after the
      procedure and in 89% at 2 years. Analysis of the data suggests that patients with
      pretreatment PSA levels less than 10 ng/mL had the best outcomes. There were no
      disease-related deaths; the predominant morbidity was short-term bladder and
      bowel irritation without permanent sequelae. Incontinence occurred in less than
      5% of patients who had undergone prior transurethral resection of the prostate.
      Impotence occurred in less than 15% of patients. CONCLUSIONS: The technique used
      in this study proved effective in reducing PSA levels to less than 1.5 ng/mL and
      in producing negative biopsies 1 and 2 years postoperatively. Results are
      comparable to external-beam radiation therapy, demonstrating a significant
      reduction in morbidity.

PMID- 9610595
TI  - Development of monoclonal antibodies specific for human glandular kallikrein
      (hK2): development of a dual antibody immunoassay for hK2 with negligible
      prostate-specific antigen cross-reactivity.
AB  - OBJECTIVES: Human glandular kallikrein (hK2) is a protein that is 80% homologous
      to prostate-specific antigen (PSA), and, like PSA, is localized to the prostate.
      We developed a specific immunoassay for hK2 that can be used to evaluate its
      clinical diagnostic utility. METHODS: We developed monoclonal antibodies (mAbs)
      specific for hK2 by immunizing with hK2 and screening for clones reactive with
      hK2 and not PSA. Prototype sandwich assays using these mAbs were tested, and the
      optimum pair selected. Purified hK2 was used as standard and PSA cross-reactivity
      was assessed in the assay. Both hK2 and hK2-alpha1-antichymotrypsin (ACT)
      complexes have been identified in sera of patients with prostate cancer (PCa).
      Serum samples (n = 671) from healthy volunteers and patients with prostate
      disease were assayed for hK2 and PSA levels. RESULTS: The assay had a detection
      limit of less than 0.12 ng/mL and a less than 0.5% cross-reactivity with PSA. The
      assay preferentially detected free hK2 with a 3.5-fold higher molar response than
      with hK2-ACT. The mean serum concentration of hK2 in normal control samples was
      low (0.33 and 0.37 ng/mL for normal healthy men and women, respectively) but was
      elevated in patients with prostate disease (0.86 and 6.77 ng/mL for patients with
      benign prostatic hyperplasia and PCa, respectively). Negligible cross-reactivity
      to hK2 was measured by Tandem PSA assays (Hybritech). CONCLUSIONS: Significant
      concentrations of hK2, relative to PSA, were detected in human serum, especially
      in patients with prostate disease. Serum hK2 concentrations were not proportional
      to PSA concentration. Therefore, hK2 has the potential to be an independent and
      clinically useful marker for PCa.

PMID- 9610596
TI  - Postsurgical outcomes assessment following varicocele ligation: laparoscopic
      versus subinguinal approach.
AB  - OBJECTIVES: To prospectively compare and objectively assess the postsurgical
      outcome parameters of both laparoscopic and open subinguinal techniques for
      varicocele ligation in infertile men. METHODS: A total of 41 evaluable patients
      with a history of infertility, abnormal semen analysis, and clinically diagnosed
      varicoceles underwent surgical ligation either by the insufflative
      intraperitoneal laparoscopic (n = 15), gasless laparoscopic (n = 7), or the open
      subinguinal (n = 19) approach. Most procedures (39 of 41) were performed in the
      outpatient setting, and patients were followed postoperatively for a minimum of 6
      months. Postsurgical outcome was assessed by physical examination and review of a
      patient questionnaire quantifying the graded pain severity, analgesic
      requirements, and number of days to return to work. RESULTS: The average
      operative time was 82.3 +/- 26.5 minutes for insufflative intraperitoneal
      laparoscopic varicocelectomy, 170 +/- 55 minutes for gasless laparoscopic
      varicocelectomy, and 35.6 +/- 13.5 minutes for the open subinguinal approach. The
      analgesic requirement was 13.7 +/- 9.9 tablets for the insufflative laparoscopic
      group, 22.5 +/- 11 tablets for the gasless laparoscopic group, and 10.9 +/- 10.3
      tablets for the open subinguinal group. The average number of days to return to
      work was 4.9 +/- 2.7 for the insufflative group, 6.6 +/- 2.6 for the gasless
      group, and 5.1 +/- 3.7 for the open subinguinal group. CONCLUSIONS: These results
      show no superiority of laparoscopic techniques over the standard open subinguinal
      technique with respect to hospital stay, analgesic requirements, or return to
      work. Laparoscopic techniques require excessive operative time, may have
      attendant complications, and require general anesthesia, limitations that
      preclude their routine application in varicocele ligation. However, the
      laparoscopic approach may have a role in the setting of other concurrently
      performed laparoscopic procedures.

PMID- 9610597
TI  - Identification of spermatozoa and round spermatids in the ejaculates of men with
      spermatogenic failure.
AB  - OBJECTIVES: As many as 10% of infertile men have azoospermia caused by
      spermatogenic failure or ductal obstruction. The histologic diagnoses associated
      with spermatogenic failure--Sertoli cell-only syndrome, maturation arrest, and
      hypospermatogenesis--do not necessarily represent global changes in the affected
      testis, as occasional seminiferous tubules may still produce mature germ cells.
      Intracytoplasmic sperm injection (ICSI) allows individual sperm that have been
      isolated from testicular tissue to fertilize oocytes. This study assessed whether
      mature germ cells (either round spermatids or spermatozoa) were present in the
      ejaculates of patients with spermatogenic failure. METHODS: All semen analyses
      performed at our tertiary care institution from January 1993 through December
      1995 were reviewed to identify azoospermic men with spermatogenic failure. During
      this period, our laboratory employed Nuclear-Fast Red and picroindigocarmine
      staining (NF-PICS) of cytospin slides to identify rare spermatozoa and spermatids
      in otherwise azoospermic ejaculates. RESULTS: Of 3005 analyses reviewed, 20
      azoospermic men whose infertility was solely attributable to spermatogenic
      failure were identified. The histologic diagnoses were germinal cell aplasia (n =
      7), complete maturation arrest (n = 6), incomplete maturation arrest (n = 3), and
      hypospermatogenesis (n = 4). Using the NF-PICS technique, mature germ cells were
      identified in the ejaculates of 15 men (75%), and 9 men (45%) had fully formed
      spermatozoa present. CONCLUSIONS: In the clinical management of azoospermic
      infertile men, the NF-PICS technique may be used to identify men who have some
      degree of testicular spermatogenesis. This might obviate the need for the purely
      diagnostic testis biopsy that is performed before therapeutic biopsy for
      testicular sperm extraction in conjunction with ICSI.

PMID- 9610598
TI  - A quantitative histologic analysis of collagen subtypes: the primary obstructed
      and refluxing megaureter of childhood.
AB  - OBJECTIVES: To analyze and identify collagen subtypes in the primary obstructed
      and refluxing megaureter of childhood. METHODS: Anticollagen monoclonal
      antibodies to collagen types I, III, and IV were used in control ureters (n = 4),
      obstructed (n = 7), and refluxing (n = 13) megaureters. Additionally, all were
      stained with Masson's trichrome to further define the extracellular matrix. After
      staining and serial sectioning, representative ureteral sections, focusing on the
      muscularis and lamina propria regions, were digitized and analyzed with a color
      image analysis system. RESULTS: Immunohistochemical studies demonstrated
      increases in collagen types I and III for both obstructed and refluxing
      megaureters compared with controls (P <0.05). Collagen type IV was not detected
      in statistically significant amounts in any ureter. In control ureters most was
      type I (83% +/- 9%) collagen. Obstructed megaureters produced similar results
      with virtually all collagen being type I (84% +/- 26%) with very little type III
      collagen present, 5.3% +/- 3%. Refluxing megaureters contained only 55% +/- 15%
      type I collagen. However, there was an increase in type III collagen (16% +/- 4%)
      versus (4.5% +/- 2%) in controls (P <0.05). CONCLUSIONS: These data suggest that
      the greater contribution of type III collagen may play a role in the
      pathophysiology of refluxing megaureters. Because type III collagen is a less
      distensible fiber, it may cause an intrinsically stiffer ureter and play a role
      in the lower surgical success in the reimplantation of refluxing megaureters.

PMID- 9610599
TI  - Patient positioning for radical retropubic prostatectomy.
AB  - Proper positioning of a surgical patient reduces morbidity and mortality. We
      describe a method of patient positioning involving elevation of the lower
      extremities and protection of the brachial plexus that reduces complication rates
      in radical retropubic prostatectomy.

PMID- 9610600
TI  - Direct vision bladder catheterization using a short rigid ureteroscope.
AB  - We describe the use of a short, rigid ureteroscope to place a Foley catheter into
      the bladder under direct vision. The Circon ACMI MICRO-6 short ureteroscope was
      passed through a 22F Foley catheter modified with a catheter punch device. The
      catheter was placed rapidly and without difficulty in 2 patients with significant
      undermining of the trigone after transurethral incision of the prostate. This
      technique is rapid, simple, and avoids the potential complications of blind
      catheter placement following difficult transurethral procedures.

PMID- 9610601
TI  - Renal vein thrombosis secondary to absent inferior vena cava.

PMID- 9610602
TI  - Endoscopic incision of a seminal vesicle cyst.

PMID- 9610603
TI  - Lymphocele after retroperitoneal surgery for testicular or extragonadal germ cell
      tumors may mimic recurrence.

PMID- 9610604
TI  - Periurethral pseudocyst following cystoscopic collagen injection.
AB  - Periurethral injection of collagen is widely used for treatment of stress urinary
      incontinence. It has been shown to be an effective, low risk, minimally invasive
      surgical procedure to treat carefully selected patients with intrinsic sphincter
      deficiency. Adverse reactions and complications from this technique are rare. We
      report an unusual complication following cystoscopic injection of collagen.

PMID- 9610605
TI  - Rare association of renal angiomyolipoma and oncocytoma.
AB  - The association of renal angiomyolipoma and renal oncocytoma in the same kidney
      is rare, only 7 cases having been previously reported. We report a 69-year-old
      woman affected by the simultaneous presence of renal angiomyolipoma and
      oncocytoma in the right side with a decrease of renal function on the left side
      due to a stenosis of the superior polar branch that was successfully treated
      preoperatively by angioplasty. An enucleation of renal masses on the right side
      was performed with renal function preservation after 2 years.

PMID- 9610606
TI  - Seminal vesicle cystadenoma: a case report and literature review.
AB  - Primary tumors of the seminal vesicle are rare; most reported cases are
      carcinomas, with occasional reports of primary seminal vesicle sarcoma and an
      uncommon group of mixed epithelial-stromal tumors. The latter have been variably
      reported in the literature as cystadenoma, phyllodes tumor, and mullerian
      adenosarcoma-like tumor. We describe a 37-year-old man who presented with
      symptoms of bladder outlet obstruction and was found to have a pelvic mass.
      Resection of the mass yielded a biphasic tumor characterized by cystically
      dilated glandular spaces admixed with spindle-shaped stromal cells. There was no
      significant cytologic atypia or mitotic activity. The histologic features are
      most consistent with the reported cases of cystadenoma. The patient is alive,
      with no evidence of disease, 6 months after surgery. This case adds to the
      gradually growing body of literature on mixed epithelial-stromal tumors of the
      seminal vesicle.

PMID- 9610607
TI  - Hepatic subcapsular extension of pelvic lymphocele after radical retropubic
      prostatectomy.
AB  - Lymphoceles are a rare symptomatic complication after radical prostatectomy
      occurring in less than 5% of cases. We present a case of a symptomatic lymphocele
      that occurred after a radical retropubic prostatectomy and obturator
      lymphadenectomy. The lymphocele dissected along the retroperitoneum and extended
      into the hepatic subcapsular space and became secondarily infected with Candida
      albicans.

PMID- 9610608
TI  - Role of the matrix metalloproteinase and tissue inhibitors of metalloproteinase
      families in noninvasive and invasive tumors transplanted in mice with severe
      combined immunodeficiency.
AB  - OBJECTIVES: To elucidate the role of matrix metalloproteinases (MMPs) and tissue
      inhibitors of metalloproteinases (TIMPs) in human urothelial cancers, we studied
      gene expressions of MMPs, TIMPs, and membrane-type 1 matrix metalloproteinase
      (MT1-MMP) in noninvasive or invasive tumor lines transplanted in mice with severe
      combined immunodeficiency (SCID). METHODS: The UCT-1 tumor line, derived from
      bladder cancer, is a noninvasive transplantable tumor with no evidence of
      metastasis. The UCT-2 tumor line, derived from a renal pelvic tumor, extensively
      invades without metastasis. We examined gene expressions of MMPs-1, 2, 3, 7, 8,
      9, 10, and 11, TIMPs-1, 2, and 3, and MT1-MMP in UCT-1 and 2 by semiquantitative
      polymerase chain reaction analysis. RESULTS: Significantly higher gene expression
      of MMP-2 was detected in the invasive UCT-2 tumor line than in the noninvasive
      UCT-1 tumor line. Although both tumor lines expressed TIMP-1 and MT1-MMP,
      stronger gene expression of MT1-MMP was observed in the UCT-2 tumor line than in
      the UCT-1 tumor line. The other MMPs or TIMPs were not detected in either of the
      lines. CONCLUSIONS: MMP-2 and MT1-MMP may have an important role in the invasion
      mechanism of urothelial cancers.

PMID- 9610609
TI  - Hepatocarcinogenesis in liver cirrhosis: imaging diagnosis.
AB  - Hepatocellular carcinoma (HCC) frequently occurs in association with liver
      cirrhosis, as chronic liver disease is one of the most important factors in
      carcinogenesis. In addition to HCCs, recent reports of pathologic studies of
      resected specimens from cirrhotic liver describe associated small nodular lesions
      such as regenerative nodule, dysplastic nodule (adenomatous hyperplasia), and
      dysplastic nodule with subfocus of HCC (early HCC). In hepatocarcinogenesis of
      the cirrhotic liver, a regenerative nodule might be the first step in the
      development of HCC, going through phases of dysplastic nodule, early HCC and
      early advanced HCC in a multistep fashion. Fortunately, recent advances in
      various imaging techniques have facilitated the verification of these nodules. In
      this review, new nomenclature of small hepatocellular nodules, and detection and
      characterization of hepatic nodules in carcinogenesis with various imaging
      techniques are described with focus on the premalignant lesions and early stage
      of HCC. In addition, the efficacy of various imaging techniques for diagnosing
      them is discussed. Although the terms and definitions of these nodules are still
      variable and controversial, familiarity with the concept of these borderline
      lesions is important.

PMID- 9610610
TI  - Abnormal ventricular looping and abnormal laterality of the atrial chambers are
      the main morphogenetic mechanisms of cardiac lesions in cultured rat embryos
      treated with retinoic acid.
AB  - To establish the early morphogenetic mechanism in retinoid induced cardiac
      lesions, we investigated the morphology of the heart in cultured rat embryos
      treated with retinoic acid (RA) at 9.0 and 9.5 days post coitum (d.p.c). Wistar
      rat embryos were treated with RA (2 x 10(-7) M) for 6 hours from the embryonic
      day equivalent of 9.0 or 9.5 d.p.c. After further culture in an RA free medium
      for 2.5 days, embryos were fixed and examined with a stereomicroscope and a
      scanning electron microscope. Sixty three embryos were treated at 9.0 d.p.c., 14
      embryos were treated at 9.5 d.p.c. and 30 embryos were used as control. Abnormal
      ventricular looping was seen in 31 embryos (49.2%) from the group treated at 9.0
      d.p.c., and isomerism of right appendages occurred in 15 (23.8%). Embryos treated
      with RA at 9.5 d.p.c. showed a low incidence of abnormal ventricular looping
      (14.3%). We could summarize those abnormal looping as three variants of each
      looping. The mildest form was hypoplasia of the right ventricle observed in 20
      cases. Both the right and left ventricles in the second variant were shifted far
      to the left or right (10 cases). The third variant was a heart with generalized
      hypoplasia of both ventricles (3 cases). The incidence of branchial arch
      anomalies was higher at 9.5 d.p.c. than at 9.0 d.p.c. (71.4% and 30.2%,
      respectively). Abnormalities in the ventricular looping and the atrial laterality
      at 9.0 d.p.c. suggest that RA induces derangement in the development of
      laterality, while at 9.5 d.p.c., the abnormality of the migration of neural crest
      cells is the principal mechanism.

PMID- 9610611
TI  - In vitro inhibition of biophysical surface properties and change in
      ultrastructures of exogenous pulmonary surfactant by albumin or fibrinogen.
AB  - In order to observe the effects of serum albumin and fibrinogen on biophysical
      surface properties and the morphology of pulmonary surfactant in vitro, we
      measured the surface adsorption rate, dynamic minimum and maximum surface tension
      (min-, max-ST) by Pulsating Bubble Surfactometer, and demonstrated
      ultrastructures on a series of mixtures with varying concentrations of albumin or
      fibrinogen and Surfactant-TA. The albumin and fibrinogen significantly inhibited
      the adsorption rate and ST-lowering properties of surfactant through increasing
      STs of adsorption rate, min-ST, and max-ST. The characteristic morphology of the
      Surfactant-TA changed from lamellar rod-like structure with open ends into
      spherical structures with loss of their open ends by mixing with albumin or
      fibrinogen. These inhibitory effects of albumin and fibrinogen on surface
      properties of surfactant were dependent upon the increasing concentration of
      albumin or fibrinogen. We concluded that albumin and fibrinogen significantly
      altered surfactant function and its ultrastructural morphology in vitro. These
      findings support the concept that albumin and fibrinogen-induced surfactant
      dysfunction may play an important role in the pathophysiology of adult
      respiratory distress syndrome, and this adverse effect of albumin and fibrinogen
      on surfactant might be overcome by administration of large doses of exogenous
      surfactant.

PMID- 9610612
TI  - Recognition of Pneumocystis carinii antigen on its surface by
      immunohistochemistry and immunoelectron microscopy.
AB  - The aim of this study was to detect the surface antigens in different stages of
      experimental induced Pneumocystis carinii in Sprague-Dawley rats.
      Immunohistochemical staining with monoclonal (900, 902 and 904) and polyclonal
      (SP-D) antibodies demonstrated that the P. carinii organisms were mostly in the
      alveolar lumina. The binding sites of the monoclonal (900, 902 and 904) and
      polyclonal (SP-D) antibodies developed against P. carinii were examined at the
      ultrastructural level by using a post-embedding immunogold labeling. The gold
      particles were observed evenly on the surface of precyst and cyst stages of the
      P. carinii. In the trophozoite stage, scattered gold particles were seen on the
      pellicles and tubular expansions. The monoclonal antibodies reacted mainly with
      pellicles of P. carinii, whereas SP-D labeled pellicles, intracystic bodies,
      cytoplasms of alveolar macrophages, free floating surfactant material in the
      alveolar spaces, and adjacent type II epithelial cells. In the immunogold
      labeling, basically no significant differences were found in the precyst, cyst,
      and ruptured cyst stages. These results indicate that the gold particles were
      observed adhering to every stage of P. carinii, mostly concentrated on the
      pellicles, and more concentrated in the precyst or cyst stage than trophozoite
      stage which may be due to an increase in antigen accumulation during development
      from the trophozoite to the cyst.

PMID- 9610613
TI  - Prevalence and risk factors of urinary stones in Koreans.
AB  - To estimate the prevalence of urinary stone disease in Koreans, and to determine
      the inter-relationships between urinary stone disease and various epidemiological
      factors, 1,521 controls and 1,177 cases with urinary stones were evaluated. Of
      special interest in this study were: 1) proportion of past urinary stone history
      among controls; 1.9% 2) the point prevalence rate of urinary stones among
      controls; 0.2% 3) the recurrence rate of urinary stones (the proportion of past
      history of urinary stone) among cases; 56.8% 4) high incidences (76.3%) in the
      thirties to the fifties among cases 5) the risk factors for urolithogenesis;
      obesity [higher than 25 of BMI (body mass index, weight/height2)], more than 10
      year-experience as a production worker, past stone history, familial stone
      history, low physical activity (< 2,000 Kcal/day), and low intake of fruit.
      However, the well-known risk factors for urinary stones; over intake of meat or
      fish and milk or dairy products, perspiration, amount and kind of drinking water,
      and stress unexpectedly were not significantly different between the controls and
      the cases.

PMID- 9610614
TI  - Heterogeneity of IgE response to TDI-HSA conjugates by ELISA in toluene
      diisocyanate (TDI) -induced occupational asthma (OA) patients.
AB  - Toluene diisocyanate (TDI), a low molecular weight reactive chemical, is known to
      be a main cause of occupational asthma (OA) in Korea. Although it is thought that
      inhaled TDI may act as a hapten, the precise mechanisms of TDI-induced OA are
      unknown. In this study, TDI-human serum albumin (HSA) conjugates (5, 10, 20 and
      30 min) were prepared in the range of 1.5 to 5.0 TDI mole/HSA mole. Specific
      binding of serum IgE to TDI-HSA (30 min) was observed using IgE ELISA as well as
      ELISA inhibition assay. Around 40% of TDI-induced OA patients were positive for
      serum specific IgE by ELISA. Degrees of serum IgE binding were different
      depending on which TDI-HSA conjugate was used as an antigen. Moreover, binding
      patterns were different depending on the individuals. Interestingly, higher
      binding of IgE to TDI-HSA (5 min) than to TDI-HSA (30 min) which was more highly
      substituted was observed in some patients. Probably new antigenic epitopes on
      carrier proteins were targets of the specific IgE. The results of this study
      indicated that IgE responses to TDI-HSA conjugates were heterogeneous in TDI
      induced OA patients and self-proteins modified by reactive chemicals can become a
      major target antigen of IgE in certain cases.

PMID- 9610615
TI  - Nuclear overexpression of bcl-2 oncoprotein during the progression of human
      stomach cancer.
AB  - We unexpectedly observed strong nuclear overexpression of bcl-2 protein in
      advanced stomach cancer. As far as we know, such expression has not yet been
      reported. To investigate the significance of nuclear expression of bcl-2 protein
      in gastric carcinoma, we immunohistochemically analyzed bcl-2 overexpression in a
      gastric carcinogenic sequence, including 19 tubular adenomas (TA), 20 early
      carcinomas (EGC), and 20 advanced carcinomas (AGC). While TA displayed a specific
      granular and supranuclear cytoplasmic staining pattern, adenocarcinomas showed a
      strong nuclear staining pattern. Nuclear staining of bcl-2 was observed in 50% of
      AGC, 30% of EGC, and 10% of TA; cytoplasmic staining, on the other hand, was
      observed in all TA, 5% of EGC, and 10% of AGC. Nuclear bcl-2 overexpression
      differed according to the histologic type of AGC, occurring in 67% of the diffuse
      type and 25% of the moderately-to-well differentiated type. In the diffuse type,
      nuclear bcl-2 positive AGC predominated. In metastatic lesions, the pattern of
      bcl-2 immunostaining was almost identical to that seen in primary tumor. These
      results suggest that nuclear expression of bcl-2 may be related to malignant
      transformation in the stomach and is frequently associated with diffuse type
      advanced gastric adenocarcinomas.

PMID- 9610616
TI  - Detection of MYC gene amplification in malignant lymphomas.
AB  - The role of oncogene or tumor supressor gene in Epstein-Barr virus (EBV)
      associated malignant lymphomas (MLs) is poorly understood. We examined 36 MLs (21
      EBV positive and 15 EBV negative) and 6 reactive hyperplasias for the presence of
      myc gene amplification. Polymerase chain reaction (PCR) technology was used to
      examine the state of amplification of the proto-oncogene c-myc in formalin-fixed
      paraffin-embedded tissues. Variable degrees of myc gene amplification were
      detected in reactive hyperplasias and MLs. However, significant increase of c-myc
      copy numbers above 3 times were only found in 12 out of 31 non-Hodgkin's MLs
      (38.7%), in which 6 cases were EBV positive and 6 cases were EBV negative. In
      conclusion, myc gene amplification appears to play a part in MLs but no
      correlation was found between EBV infection and myc gene amplification.

PMID- 9610617
TI  - Chemokines, osteopontin, ICAM-1 gene expression in cultured rat mesangial cells.
AB  - To investigate whether MCP-1, CINC, RANTES, osteopontin and ICAM-1 mRNA could be
      induced in cultured rat mesangial cells by interleukin-1beta(IL-1beta), tumor
      necrosis factor-alpha (TNF-alpha) and lipopolysaccharide (LPS), and whether MCP-1
      and CINC gene expression could be modulated by dexamethasone, Northern blot
      assays were performed. IL-1beta induced MCP-1, CINC, RANTES and ICAM-1 gene
      expression in a time dependent manner. IL-1beta-induced MCP-1, CINC and ICAM-1
      mRNA amount were maximal at 3 hours exposure around 14.5, 15.7, 2.2 folds
      increase and IL-1beta-induced RANTES mRNA at 24 hours around 2.0 folds. TNF-alpha
      and LPS also induced MCP-1 and ICAM-1 gene expression. TNF-alpha also induced
      RANTES gene expression but LPS did not. On the other hand, IL-1beta, TNF-alpha
      and LPS had little effect on osteopontin gene expression but fetal calf serum
      could increase osteopontin mRNA. Dexamethasone suppressed the IL-1beta-induced
      MCP-1 and CINC mRNA. These results suggest that, through these gene expressions,
      mesangial cells are able to communicate directly or indirectly with macrophages
      or neutrophils, which may lead to glomerulosclerosis.

PMID- 9610618
TI  - Different protein-binding patterns in the P3 promoter region of the human insulin
      like growth factor II gene in the human liver cirrhosis and hepatocellular
      carcinoma tissues.
AB  - The P3 promoter of the human insulin-like growth factor II (IGF-II) is the major
      IGF-II promoter in fetal liver (FL) and hepatocellular carcinoma (HCC). However,
      little information is available on the transcriptional factors (TFs) controlling
      IGF-II gene expression in human liver cirrhosis (LC) and HCC tissues. To evaluate
      the protein-binding patterns in the P3 promoter region, we performed
      electromobility shift assay (EMSA) and DNase I footprinting assay using nuclear
      extracts from human FL, LC and HCC tissues. EMSA showed considerable differences
      in binding patterns of proteins to P3 promoter region according to different
      nuclear extracts used in this study. By footprinting assay, eight footprints were
      observed in extracts. In addition, LC extract showed two specific binding at L1 [
      80:+30] and L2 [-126:-80] regions, and HCC showed two specific binding at H1 [
      176:-120] and H2 [-210:-177] as well as two liver specific binding (L1 and L2).
      Footprinting after immunoprecipitation indicates that Egr1, Egr2 and Sp1 could
      bind to P3 promoter directly, while c-jun and c-fos could not bind to these
      region directly. Further study is required to determine the function of these
      proteins.

PMID- 9610619
TI  - Prenatal molecular evaluation of six fetuses in four unrelated Korean families
      with ornithine transcarbamylase deficiency.
AB  - Ornithine transcarbamylase (OTC) deficiency, an X-linked inborn error of the urea
      cycle, leads to the accumulation of ammonia, causing neurologic deficits.
      Clinical management for the patients with OTC deficiency is frustrating and
      requires a burdensome medical regimen, since they may have impairment and
      recurrent episodes of hyperammonemia in spite of intensive care. Therefore,
      prenatal diagnosis of the affected fetus is important in genetic counselling for
      the family at high risk. In this study, mutations in the OTC gene of three
      obligate heterozygotes and a proband have been identified in four unrelated
      families: R141Q, R320X, H214Y, M205T. Each mutation altered restriction
      recognition sites; TaqI for R141Q, NlaIII for M205T, RsaI for H214Y, BclI for
      R320X. Based on their molecular defects, prenatal diagnoses of 6 fetuses
      including one set of fraternal twins were successfully made at the ninth to
      eleventh week of gestation by polymerase chain reaction (PCR)-restriction
      digestion using genomic DNA from chorionic villus sampling (CVS). We predicted
      the outcome of all fetuses prenatally. Among six, four were females and two were
      males, which were determined by PCR amplification of the sex determining region
      of the Y chromosome (SRY) gene. Each carried a wild type allele for the
      corresponding mutant allele. They were also tested postnatally for the mutations
      to be unaffected.

PMID- 9610620
TI  - Hereditary protein C deficiency with recurrent thrombosis: identification of a
      missense mutation (C6218T).
AB  - Protein C is the central component of a major anti-thrombotic regulatory system
      and individuals with hereditary protein C deficiency (PCD) tend to have an
      increased risk of thromboembolism. During the last several years, mutations
      causing PCD have been identified in Western countries and in Japanese. In the
      present study, we report a case of hereditary PCD with a missense mutation
      (C6218T) in a 44 year old female with recurrent pulmonary thromboembolism. The
      protein C activity (35%) and antigen (58%) levels in this patient were decreased.
      Furthermore, we have identified the same molecular defect and PCD in other
      asymptomatic family members including proband's mother and two daughters and one
      son. To our knowledge, this is the first case of hereditary PCD with identified
      genetic defect in the Korean population, which may be one of hot spots for
      mutation in the protein C gene.

PMID- 9610621
TI  - Malignant eccrine spiradenoma with florid squamous differentiation.
AB  - Malignant eccrine spiradenoma (MES) is an exceedingly rare neoplasm of cutaneous
      adnexal origin. To date, 31 cases have been documented in the literature. We
      herein report an additional case of MES that arose in longstanding eccrine
      spiradenoma (ES). A 54-year-old woman was seen for a bluish nodular mass on the
      right flank that previously had been stable for 7 to 8 years and had recently
      increased in size and become tender. The excised mass (2.8 x 2.5 x 2.5 cm) had no
      attachment to the overlying epidermis. Microscopically, 2 to 3 sharply demarcated
      lobules were surrounded by a markedly thickened and hyalinized fibrous capsule.
      Of the lesion removed, approximately 20% of the tumor showed typical histologic
      features of benign ES. In the remaining malignant areas, the typical
      configuration of benign counterpart, consisting of peripheral rows of small dark
      basaloid cells and central layers of large pale cells partially forming lumina,
      was replaced with a massive solid proliferation of large pale cells showing
      nuclear pleomorphism, prominent nucleoli, increased mitotic activity (reaching
      12/10 HPF) and loss of PAS-positive basement membrane. There were multiple foci
      of florid squamous differentiation in the malignant portion. Cytokeratin, focally
      S-100 and EMA were expressed in large pale cells, whereas alpha smooth muscle
      actin and S-100 were positive in small dark basaloid cells. Focal reactivity of
      CEA and EMA was found in the central lumina. P53 was not expressed in benign
      areas, whilst in malignant areas an occasional nuclear reaction was disclosed.

PMID- 9610622
TI  - Acetazolamide-responsive hereditary paroxysmal ataxia: report of a family.
AB  - Hereditary paroxysmal ataxia is a rare dominantly inherited disorder
      characterized by recurrent attacks of cerebellar ataxia, dysarthria, and
      nystagmus. Each attack lasts from several minutes to few hours or days. Usually
      there are no motor difficulties between attacks. We report a patient who had had
      recurrent ataxic episodes since early childhood. Four members of the family over
      two generations had similar attacks. There were no abnormalities in the
      laboratory studies including plasma amino acid, lactate, pyruvate, and EEG.
      Treatment with acetazolamide resulted in complete abolition of the attacks.
      Because of its dramatic response to acetazolamide, the recognition of this rare
      disorder is important.

PMID- 9610623
TI  - Short-rib polydactyly syndrome, Beemer-Langer type, with bilateral huge
      polycystic renal dysplasia: an autopsy case.
AB  - Short rib-polydactyly syndrome (SRPS) is a group of lethal skeletal dysplasia of
      an autosomal recessive inheritance characterized by markedly narrow ribs,
      micromelia, and multiple anomalies of major organs. We report a case of type IV
      SRPS with uncommon associations of polydactyly and bilateral polycystic kidneys,
      in a 28 week old female fetus. She was born dead to a 28 year old mother, showing
      a hydropic change, narrow thorax, and shortened limbs with postaxial
      heptasyndactyly of both hands and feet. Radiologic examination revealed short
      horizontal ribs, curved short tubular limb bones, small ilia and scapula, and a
      mild vertebral abnormality. Postmortem examination disclosed pulmonary
      hypoplasia, pancreatic cysts, hepatic fibrosis, and left persistent superior vena
      cava. In addition this case had bilateral huge polycystic renal dysplasia that
      was seldom described in any type of SRPS. Histologic sections of the vertebrae
      disclosed abnormal enchondral ossification with irregular and retarded
      hypertrophic zone.

PMID- 9610624
TI  - Malignant mixed Mullerian tumor (homologous type) of the adnexa with
      neuroendocrine differentiation: a case report.
AB  - Malignant mixed mullerian tumors (MMMT) are unusual neoplasms occurring mostly in
      the uterus. In the ovary, they are very rare and represent fewer than 1% of all
      ovarian malignancies; in the salpinx, they are even rarer than those of the
      ovary. We report a carcinosarcoma of the left adnexa having features of
      neuroendocrine differentiation in a 69-year-old female. The tumor contained both
      adenocarcinoma and squamous cell carcinoma having dear cell change admixed with
      an undifferentiated malignant mesenchymal component. The sarcoma components
      consisted of spindle cells, small-round cells and bizarre giant cells mimicking
      rhabdomyoblast. Almost all of the carcinomatous glandular components and some
      foci of the squamous cell and undifferentiated carcinomatous components were
      focal positive for S-100 protein, chromogranin, neuron specific enolase,
      synaptophysin and Leu-7. Electron microscopy revealed membrane-bound
      neurosecretory granules in the cytoplasm of some glandular epithelial cells.
      Histologically, the tumor involved the left adnexa, abdominal peritoneum, surface
      of the bladder dome, omentum and left external iliac lymph node (stage IIIc).

PMID- 9610625
TI  - Glycogen storage disease type IV: a case report.
AB  - Glycogen storage disease type IV (GSD-IV) is a rare autosomal recessive disease
      caused by deficient glycogen branching enzyme (GBE). We report a 15-month-old
      female patient with GSD-IV who exhibited an abdominal distension and failure to
      thrive for 9 months. The patient showed hepatosplenomegaly with massive ascites.
      The laboratory findings showed abnormal liver functions including prolongation of
      prothrombin time and partial thromboplastin time. The light microscopic and
      electron microscopic findings of the liver biopsy specimen were consistent with
      GSD-IV. Measurement of glycogen quantity in the red blood cells showed increased
      storage of glycogen in the patient and interestingly, in her mother. The GBE
      activity of the patient's red blood cells was undetectable. The patient's
      ascites, general condition, and laboratory findings have been improved with
      supportive treatment with diuretics and a low dose of prednisolone.

PMID- 9610626
TI  - Emphysematous cystitis.
AB  - Emphysematous cystitis is characterized by gas collection within the bladder wall
      and lumen. We report two cases of emphysematous cystitis of the urinary bladder
      in a 67-year-old and a 63-year-old women. They presented with bladder irritation
      symptoms such as dysuria, hematuria and frequency. Urinalysis showed pyuria.
      Cystoscopic examination revealed that bladder mucosa was studded with vesicles
      varying in size and arranged in clumps. CT scans of the pelvis showed mottled gas
      bubbles within the bladder. They were treated with antibiotics. Four days after
      the treatment, the symptoms subsided and plain abdominal film showed no evidence
      of gas shadows in the pelvic cavity.

PMID- 9610627
TI  - Eosinophil-induced chronic hepatitis.
AB  - Chronic hepatitis associated with hypereosinophilia has been very rarely reported
      worldwide. A 7-month-old male infant presented with a high fever, cough, non
      projectile vomiting and hepatomegaly. The eosinophil count of the peripheral
      blood increased up to 21,500/mm3 (49% of WBC). The infant had a history of
      frequent contact with a neighbor keeping a pigsty. The pathologic examinations of
      the liver showed severe porto-periportal necroinflammation with marked
      eosinophilic infiltration, giant cell transformation and ballooning degeneration
      of hepatocytes, and degranulation of the eosinophils. Bone marrow showed
      increased eosinophils and decreased myeloid series. Pericardial effusion and
      bilateral pulmonary consolidation were noted. Corticosteroid aggravated the
      clinical symptoms of the infant. Anthelmintic treatment significantly normalized
      the eosinophil count and liver function tests, but cardiopulmonary manifestations
      continued.

PMID- 9610628
TI  - A case of spontaneous cervical and mediastinal emphysema.
AB  - Subcutaneous cervical and mediastinal emphysema usually can occurs as a result of
      surgery or trauma. Spontaneous cervical subcutaneous emphysema and
      pneumomediastinum, occurring in the absence of previous disorders or provocating
      factors, is very rare. The following case report of spontaneous cervical and
      mediastinal emphysema is assumed to be the first of its kind in Korea. The
      patient has been followed up for three years without recurrence or sequelae.

PMID- 9610629
TI  - Cultivation of bloodstream forms of Trypanosoma carassii, a common parasite of
      freshwater fish.
AB  - Trypanosoma carassii (syn. T. danilewskyi) is a widespread parasite of carp and
      other cyprinid as well as some noncyprinid freshwater fish. It lives
      extracellularly in the blood and tissues of its hosts, causing chronic
      infections. In this paper the isolation of T. carassii from fish blood and the
      propagation and cloning of bloodstream forms in vitro are described. By several
      criteria, cultured and fish-derived trypomastigotes are indistinguishable. The
      culture system should be useful for the biochemical characterization of this
      trypanosome and its interaction with the fish immune system.

PMID- 9610630
TI  - Compared vectorial transmissibility of pure and mixed clonal genotypes of
      Trypanosoma cruzi in Triatoma infestans.
AB  - A total of 15 mixtures involving 9 different stocks attributed to the 19/20, 32
      and 39 major clonal genotypes of Trypanosoma cruzi were used to infect third
      instar nymphs of Triatoma infestans via an artificial feeding device. Three
      biological parameters were considered: (1) the percentage of infected insects
      (%II), (2) the number of flagellates per insect (NFI), and (3) the percentage of
      trypomastigotes per insect (%DIF). Genetic characterization by both multilocus
      enzyme electrophoresis (MLEE) and random amplification of polymorphic DNA (RAPD)
      indicated that in almost all cases (87%), mixtures remained present after
      completion of the whole cycle in the insect vector. Two lines of comparison were
      performed: (1) pure clonal genotypes versus corresponding mixed clonal genotypes
      and (2) the actual behavior of mixed clonal genotypes versus the expected
      behavior of the theoretical mixture (i.e. the arithmetic mean of the results
      observed for each of the two clonal genotypes taken separately). Statistical
      analyses of the variables were made difficult because of the presence of large
      standard deviations. Nevertheless, in several cases, mixtures differed
      significantly from pure clonal genotypes, and in one case the actual mixture
      differed significantly from the theoretical mixture. In some cases, interaction
      (either potentialization or reciprocal inhibition) could be suspected.

PMID- 9610631
TI  - Trypanosomatid protozoa in plants of southeastern Spain: characterization by
      analysis of isoenzymes, kinetoplast DNA, and metabolic behavior.
AB  - Three flagellates of the family Trypanosomatidae were isolated from mango fruits
      (Mangifera indica) and from the stems of clover (Trifolium glomeratum) and
      Amaranth (Amaranthus retroflexus) in southeastern Spain and were adapted to in
      vitro culture in monophase media. The parasites showed an ultrastructural pattern
      similar to that of other species of the genus Phytomonas. Mango and clover
      isolates differed from amaranth isolates in ultrastructural terms. The isolates
      were characterized by isoenzymatic analysis and by kDNA analysis using five
      different restriction endonucleases. With eight of the nine enzymatic systems,
      mango and clover isolates were distinguished from those of amaranth.
      Nevertheless, with the enzymes malate dehydrogenase and superoxide dismutase,
      flagellates isolated from clover were differentiated from those isolated from
      mango. Electrophoretic and restriction-endonuclease analysis of kDNA minicircles
      showed similar restriction cleavage patterns for the isolates from mango and
      clover, whereas the patterns of the amaranth isolates differed. The results of
      the present study confirm that the strains isolated from mango and clover
      constitute a phylogenetically closely related group of plant trypanosomatids,
      which is more distantly related to the strain isolated from amaranth. The
      similarities in the results obtained for isolates from mango and clover foliage,
      on the one hand, and those obtained from tomato and cherimoya fruits (studied
      previously), on the other, as well as the geographic proximity of the different
      plants support the contention that only one strain is involved, albeit one strain
      that can parasitize different plants. Furthermore, some of the plants appear to
      act as reservoirs for the parasites. On the other hand, the metabolism studies
      using [1H]-nuclear magnetic resonance spectroscopy did not reveal that the
      catabolism of Phytomonas in general follows a pattern common to all the species
      or isolates. Phytomonas are incapable of completely degrading glucose, excreting
      a large part of their carbon skeleton into the medium as fermentative metabolites
      (acetate, ethanol, glycine, glycerol, and succinate).

PMID- 9610632
TI  - Effects of benzimidazole anthelmintics as microtubule-active drugs on the
      synthesis and transport of surface glycoconjugates in Hymenolepis microstoma,
      Echinostoma caproni, and Schistosoma mansoni.
AB  - Hymenolepis microstoma (Cestoda), Echinostoma caproni, and Schistosoma mansoni
      (Digenea) were exposed to benzimidazoles to determine the influence of the drugs
      on the secretion of glycoconjugates that protect the worms' surface. Worms were
      obtained from mice treated with mebendazole or albendazole, and the
      glycoconjugates were localized in the parasite tissues by cytochemistry using
      lectin-gold conjugates. Events leading to the death of H. microstoma and E.
      caproni extended over a medication period for at least 2-3 days, and the
      following interrelated phases were discernible. Upon depolymerization of the
      microtubules the tegumentary cytons continued to synthesize glycoconjugates for
      up to about 24 h. Vesicles containing the glycans accumulated in the cytons, but
      their microtubule-based transport to the distal tegument was inhibited. At about
      1 day the Golgi complex became fragmented and the production of glycans sharply
      declined. As a consequence of this and an ongoing turnover of the surface coat
      the contents of glycoconjugates in the distal tegument decreased. Similar effects
      were produced by vinblastine and colchicine in vitro. In contrast, benzimidazole
      treatment of S. mansoni, which is reportedly inefficacious, did not alter the
      replenishment of the surface glycoconjugates. Diminution of the coating with
      glycoconjugates of the surface of drug-sensitive species constitutes a secondary
      effect of benzimidazoles that might, synergistically with immune mechanisms of
      the host, enhance the expulsion of the worms.

PMID- 9610633
TI  - Thin-layer chromatography and histochemistry analyses of neutral lipids in
      Helisoma trivolvis infected with four species of larval trematodes.
AB  - Thin-layer chromatography (TLC) and histochemistry studies were done on the
      neutral lipid content of the digestive gland gonad (DGG) complex of Helisoma
      trivolvis infected with four species of larval trematodes. Two of the species,
      Ribeiroia sp. and Zygocotyle lunata, contained rediae, and the two others,
      Spirorchis sp. and an armatae xiphidiocercaria, contained sporocysts. The DGG
      infected by each species had its own distinct neutral lipid profile as determined
      by TLC. All profiles differed from that of the uninfected DGG. Densitometric TLC
      studies showed some quantitative differences in free sterols in infected versus
      uninfected DGGs. Visual observations of the chromatograms showed that all four
      species caused a marked elevation in the triacylglycerol fraction in the DGG as
      compared with the uninfected controls. Oil Red O (ORO) histochemistry studies
      showed that levels of neutral lipids were increased in the DGGs of infected
      versus uninfected samples. These histochemistry studies showed a variable
      distribution of neutral fat, ranging from its absence in the cercariae of Z.
      lunata and the armatae xiphidiocercaria to ORO-positive droplets in the excretory
      system of Ribeiroia sp. Rediae and sporocysts contained ORO-positive material in
      the body wall and in the space between cercariae.

PMID- 9610634
TI  - Involvement of Trichomonas vaginalis surface-associated glycoconjugates in the
      parasite/target cell interaction. A quantitative electron microscopy study.
AB  - Cytochemical labeling with gold particle-conjugated lectins in combination with
      transmission and scanning electron microscopy was used to localise specific sugar
      residues on the Trichomonas vaginalis cell surface. For investigation of the role
      played by the surface glycoconjugates of T. vaginalis in the process of parasite
      adhesion to the target cells, selected glycan moieties of parasite surface-bound
      molecules were removed by treatment with alpha-mannosidase and beta-N
      acetylglucosaminidase. For observation of the parasite/epithelial cell
      interaction, human amnion membrane was employed as an in vitro model.
      Ultrastructure observations showed that T. vaginalis has distinct binding sites
      for concanavalin-A and wheat-germ agglutinin. This indicates the presence of
      mannose or mannose-like residues and N-acetyl-D-glucosamine-containing residues
      on the parasite membrane. The addition of inhibitory sugars to T. vaginalis
      incubation media diminished the subsequent labeling of the parasite cell coat
      with lectins. Enzyme treatment caused a significant reduction in the number of
      sugar residues on the cell surface of the parasite. The majority of the viable,
      motile, enzyme-treated T. vaginalis cells incubated with amnion membrane were
      incapable of adhering to the target cells. It was concluded that sugar residues,
      in particular alpha-D-mannose and N-acetyl-glucosamine, present in the parasite
      glycocalyx are involved in the process of T. vaginalis attachment to the host's
      epithelial cells. Removal of the T. vaginalis cell-surface sugars prevented the
      attachment to and damage of the epithelial cells.

PMID- 9610635
TI  - A study of virulence parameters for Toxoplasma gondii infections in mice.
AB  - With the aim of establishing assessments of the virulence of Toxoplasma gondii
      isolates for mice, we investigated weight loss, serum levels of haptoglobin, and
      serum levels of tumor necrosis factor-alpha (TNF-alpha) as alternative parameters
      to mouse mortality. Groups of BALB/c mice were inoculated i.p. with increasing
      parasite doses (5 x 10(1), 10(4), and 10(6)) of isolate 119 and with a low dose
      (5 x 10(1)) of isolates GT1 and NED. The inoculation dose was inversely
      correlated with the interval to the onset of weight loss (starting at days 9, 7,
      and 5, respectively) and the onset of increase in serum haptoglobin (starting at
      about days 8, 6, and 4, respectively). The GT1 strain (inducing 100% mortality at
      day 9) also gave the fastest response in terms of weight loss (onset by day 8)
      and increase in serum haptoglobin (onset by day 6), which occurred 1-2 days
      before these parameters were affected in the other low-dose groups. The low-dose
      NED and 119 inoculations were distinguished by continued weight loss, which
      lasted until day 20 in the former group (max. average weight loss 2.9 g as
      compared with 0.4 g).

PMID- 9610636
TI  - Susceptibility of BALB/c mice to nymphs and larvae of Ixodes ricinus after
      modulation of IgE production with anti-interleukin-4 or anti-interferon-gamma
      monoclonal antibodies.
AB  - BALB/c mice infested three times with nymphs or larvae of Ixodes ricinus ticks do
      not acquire resistance as assessed by evaluation of both tick attachment and the
      weight of engorged nymphs or larvae. Tick challenge causes a gradual increase in
      total IgE antibody production from the first to the third infestation. Anti-tick
      IgG antibodies are never detected. When the mice are treated with anti
      interleukin-4 (anti-IL-4) or anti-interferon-gamma (anti-IFN-gamma) monoclonal
      antibodies (mAbs) 1 day before each infestation, they produce fewer or more IgE
      antibodies, respectively. No effect is observed on IgG antibodies. In IL-4
      deficient mice, no IgE or IgG antibody is produced. However, these treatments and
      the use of IL-4-deficient mice have no negative effect on either tick attachment
      or the weight of engorged nymphs or larvae. Treatment with anti-IL-4 mAb and the
      use of IL-4-deficient mice inhibits and abolishes the switching of IgE,
      respectively, but these are apparently not sufficient to shift the response
      toward Th1 cells.

PMID- 9610637
TI  - Major histocompatibility complex class I- and II-deficient knock-out mice are
      resistant to primary but susceptible to secondary Eimeria papillata infections.
AB  - Two distinct mechanisms seem to function in reducing oocyst output during Eimeria
      papillata infections in mice. For naive mice, immunity was afforded by a T-cell
      independent gamma-interferon (IFN-gamma) response mediated by natural killer (NK)
      cells. On reinfection, resistance was associated with T-cells and, to a lesser
      extent, perforin. To determine if antigen presentation with major
      histocompatibility complex (MHC) molecules was required to control oocyst
      production by NK cells during primary infection or by T-cells during secondary
      infection, mutant mice that lacked H2-IAbeta(b) (Abeta(b)-/-) or beta2
      microglobulin (beta2m-/-) were used. Since MHC molecules are required for the
      maturation of alphabeta T-cells, Abeta(b)-/- and beta2m-/- mutant mice are also
      deficient in functional alphabeta+CD4+ or alphabeta+CD8+ T-cells, respectively.
      As compared with wild-type control mice, oocyst output by mutant mice was not
      significantly affected during primary infection, suggesting that the ability of
      NK cells to control parasite replication is not dependent on the expression of
      MHC molecules. On reinfection, differences were observed for mutant mice as
      compared with controls. Abeta(b)-/- mice were found to be more susceptible than
      beta2m-/- mice, suggesting that the alphabeta+CD4+ T-cell subset plays a greater
      role in resistance to reinfection than does the alphabeta+CD8+ T-cell subset. The
      mechanism of resistance depends on the immune status of the host and requires the
      coordinated interaction of both alphabeta+ T-cell subsets for optimal parasite
      control during subsequent infections.

PMID- 9610638
TI  - Ultrastructural effects of the chelating agent 1,10-phenanthroline on Trypanosoma
      cruzi epimastigotes in vitro.
AB  - The in vitro effects of the metal chelator 1,10-phenanthroline (OPHEN) on the
      ultrastructure of Trypanosoma cruzi epimastigotes were investigated.
      Epimastigotes treated with OPHEN display swelling and electron-dense deposits in
      the kinetoplast, mitochondrion, and cisternae of the endoplasmic reticulum. These
      morphological alterations are dose-dependent and first appear at an OPHEN
      concentration of 5.0 microg/ml. Analytical electron microscope examination
      indicates that the metallic portion of the electron-dense deposits is
      predominantly calcium.

PMID- 9610639
TI  - Trichinella spiralis: induction of the basophilic transformation of muscle cells
      by synchronous newborn larvae.
AB  - Newborn larvae (NBL) possess the "transformation potential" (TP) to induce the
      basophilic transformation of the muscle cell into the nurse cell and to create
      the nurse cell-muscle larva complex. For investigation as to whether TP is age
      dependent, three groups of synchronous NBL (sNBL) were obtained at 1 h, 9 h, and
      6 days of age, respectively, and were injected intramuscularly into mice. The TP
      was demonstrated to be high for both 1- and 9-h-old sNBL, but for 6-day-old sNBL,
      none was found. The earliest transformation of muscle cells was observed at 48 h
      postinfection (p.i.) in the first two groups of sNBL. Moreover, for 1-h-old sNBL
      the numbers of basophilically transformed muscle cells without larvae were 3-fold
      those of sNBL observed in histology sections. The results indicate that (1) due
      to the high TP observed in the 1-h-old sNBL group, NBL are born with TP; (2) the
      TP is lost by aging; and (3) the induction of the basophilic transformation of
      muscle cells is possible without direct contact between the muscle cell and NBL
      being required, as contact with released factor(s) alone may be enough.

PMID- 9610640
TI  - An enzyme-linked immunosorbent assay for detection of Theileria parva antibodies
      in cattle using a recombinant polymorphic immunodominant molecule.
AB  - Field and experimental bovine infection sera were used in immunoblots of
      sporozoite and schizont lysates of Theileria parva to identify candidate
      diagnostic antigens. Four parasite antigens of Mr 67,000 (p67), 85,000 (the
      polymorphic immunodominant molecule, PIM), 104,000 (p104), and 150,000 (p150)
      were selected for a more detailed analysis. The p67 and p104 antigens were
      present only in the sporozoite lysates, whereas PIM and p150 were found in both
      sporozoite and schizont lysates. The four antigens were expressed as recombinant
      fusion proteins and were compared with each other in an enzyme-linked
      immunosorbent assay (ELISA) and in the whole-schizont-based indirect fluorescent
      antibody test (IFAT) in terms of their ability to detect antibodies in sera of
      experimentally infected cattle. The PIM-based ELISA provided a higher degree of
      sensitivity and specificity than did the ELISA using the other three recombinant
      antigens or the IFAT. Further evaluation of the PIM-ELISA using experimental sera
      derived from cattle infected with different hemoparasites and field sera from
      endemic and nonendemic T. parva areas showed that the assay had a sensitivity of
      > 99% and a specificity of between 94% and 98%.

PMID- 9610641
TI  - Echinococcus granulosus: membrane permeability of secondary hydatid cysts to
      albendazole sulfoxide.
AB  - The objectives of the present study were, first, to establish a methodology for
      evaluation of the permeability in vitro of hydatid cysts to different drugs and,
      second, to compare the permeability to albendazole sulfoxide of cysts from
      untreated animals, cysts from animals treated with 50 mg/kg netobimin for 5 days,
      and cysts from animals treated with 50 mg/kg netobimin plus 1.1 mg/kg
      fenbendazole for 5 days. The drug flow follows the Fick law, i.e., the uptake
      occurs by simple diffusion. We calculated the permeability constant of the cyst
      membrane by taking into account the disappearance velocity constant, the cyst
      area, and the incubation solution volume. The permeability value obtained for
      albendazole sulfoxide was 8.06+/-2.30 x 10(-6) cm s(-1) in cysts from untreated
      animals, 5.56+/-2.53 x l0(-6) cm s(-1) in cysts from animals treated with
      netobimin, and 7.05+/-3.04 x 10(-6) cm s(-1) in cysts from animals treated with
      netobimin +/- fenbendazole. These permeability values show significant
      differences (P < 0.05).

PMID- 9610642
TI  - Ultrastructure of the nucleus of the Iodamoeba butschlii cyst.
AB  - The ultrastructure of the Iodamoeba butschlii cyst from human feces was studied.
      The glycogen mass appears as a compact dense body in the cytoplasm without any
      surrounding membrane. The cytoplasm has no mitochondrion. The nucleus shows a
      distinct nucleolus filled with electron-dense particles. On one side of the
      nucleolus are electron-dense cytoplasmic masses measuring 200-400 nm. The nuclear
      membrane is two-layered and shows pores.

PMID- 9610643
TI  - Sequence and preliminary characterisation of a Taenia saginata oncosphere gene
      homologue of the small heat-shock protein family.
AB  - During antibody screening of a Taenia saginata oncosphere cDNA library a clone (R
      Tso2) sharing a high degree of homology at both the DNA and amino acid levels
      with the small heat-shock protein (shsp) family was identified. The R-Tso2 clone
      was a full-length sequence (1162 bp) with an open reading frame of 945 bp and 314
      amino acids, corresponding to a deduced molecular mass of 35.6 kDa and
      isoelectric point of 5.6. R-Tso2 had the highest degree of homology with the
      Schistosoma mansoni major egg antigens, showing the characteristic shsp 100 amino
      acid sequence motif duplicated. The R-Tso2 expression product was not immuno
      precipitated by any serum from a panel of serum samples obtained from bovine,
      porcine and human hosts suffering from either T. saginata or T. solium
      cysticercosis.

PMID- 9610645
TI  - Launching your research career through postdoctoral training opportunities.

PMID- 9610644
TI  - Sequence and immunogenicity of the Taenia saginata homologue of the major surface
      antigen of Echinococcus spp.
AB  - A clone (R-Tso18) was isolated from a Taenia saginata oncosphere cDNA library by
      screening with sera from rabbits immunised with oncosphere extract. It contained
      a full-length cDNA sequence of 1893 bp with an open reading frame of 1680 bp,
      corresponding to 559 amino acids with a deduced molecular mass of 65.173 kDa and
      an isoelectric point of 6.08. The R-Tso18 protein showed 80-84% nucleotide
      identity with the major protoscolex surface antigens of Echinococcus
      multilocularis (EM10) and E. granulosus (EG10). Preliminary immunogenicity
      studies employing the radiolabeled R-Tso18 protein in immune co-precipitation
      assays indicated sero-positivity for T. saginata-infected calf sera (6/13), T.
      solium cysticercosis human (7/22) and pig (2/2) sera and E. multilocularis (6/10)
      and E. granulosus (1/12)-infected human sera, whereas other helminth-infection
      sera were negative. As immuno-precipitation is a relatively insensitive assay, it
      was concluded that further studies on the diagnostic potential of the purified
      recombinant R-Tso18 antigen, or its peptides, are merited.

PMID- 9610646
TI  - Transmural care of terminal cancer patients: effects on the quality of life of
      direct caregivers.
AB  - BACKGROUND: The burden of caring for terminal cancer patients has a negative
      effect on the informal caregivers' quality of life. OBJECTIVES: To investigate
      the effects of a transmural home care intervention program for terminal cancer
      patients on the direct caregivers' (the patient's principal informal caregiver)
      quality of life, compared with standard care programs. The intervention program
      intended to optimize the cooperation and coordination between the intramural and
      extramural health care organizations (transmural care). METHODS: Direct
      caregivers of terminal cancer patients (estimated prognosis of less than 6
      months) could be included in this quasi-experimental study. The direct
      caregivers' quality of life was measured in a multidimensional way 1 week before
      (T1), 1 week after (T2), and 4 weeks after (T3) the patient's discharge from the
      hospital (discharge being the starting point of the intervention), then again at
      3 months after the patient's death (T4). Factor analyses on the four outcome
      measures yielded one factor. This was considered the primary outcome measure and
      was named the Overall Quality of Life Index (OQOLI). RESULTS: Multiple regression
      analyses showed that the intervention contributed significantly positively to the
      direct caregivers' OQOLI at T2 (beta=.30; p < .05) and T4 (beta=.28; p < or =
      .05), compared with standard care. CONCLUSION: Transmural care forms a
      significantly positive contribution to the OQOLI of direct caregivers of terminal
      cancer patients 1 week after the patient's discharge from the hospital and 3
      months after the patient's death. Good terminal care also appears to be important
      for direct caregivers as well, with respect to perceived quality of life.

PMID- 9610647
TI  - Symptom and activities of daily living trajectory in multiple sclerosis: a 10
      year study.
AB  - BACKGROUND: Symptom control in chronic illness is not merely a matter of medical
      management as the patient and family must rely on their own judgment, wisdom, and
      ingenuity for controlling symptoms. The absence in the literature regarding the
      effects of multiple sclerosis (MS) as perceived by afflicted people and their
      family members led to the 10-year longitudinal study. OBJECTIVES: To study
      patient self-report data to determine whether particular interventions may be
      needed to enhance the individual's comfort and functional levels. METHODS: The
      chronic illness trajectory of three groups of people with MS (< or =5 years of
      diagnosis, n=49; >5 to 10 years, n=36; and >10 years, n=68) was examined over a
      10-year period. Serial self-assessments of the subjects' prevalence of MS-related
      symptoms (motor, brain stem, sensory, elimination, mental/emotional) and level of
      activities of daily living (ADL) functioning (fine and gross motor activities,
      sensory/communication, socializing/recreation, intimacy) were obtained annually.
      Profiles illustrating the subject's symptom and ADL pattern were also returned
      annually to each subject. RESULTS: Using 10-year average scores, study findings
      indicated no group differences relative to symptoms but showed significant group
      differences in all ADL functions. Separate group within-year (1, 3, 5, 7, 10)
      comparisons reflected significant increases in motor, brain stem, and elimination
      symptoms together with a decline in all ADL functions for specific groups.
      CONCLUSIONS: Medical data suggest, on average, a continuous downward trajectory
      beginning in the first years of illness or at approximately 36 to 37 years of
      age. In contrast, in this research, patient self-reports of fine and gross motor
      ADL, a correlate of neurologically based disability evaluations, reflect that
      relatively major decline begins after 5 years post-diagnosis and after age 40 for
      subjects recruited primarily from nonclinical sites.

PMID- 9610648
TI  - Predicting pressure sore risk with the Norton, Braden, and Waterlow scales in a
      Hong Kong rehabilitation hospital.
AB  - BACKGROUND: Numerous pressure sore risk calculators have been developed since the
      1960s. Each scale is claimed to have predictive value and applicability in
      various clinical settings, but it has not been determined which one is more
      relevant for adoption in a rehabilitation setting. OBJECTIVES: To compare the
      predictive power of the three most commonly adopted pressure sore risk
      calculators: Norton, Braden, and Waterlow scales. METHOD: One hundred six
      patients, free of pressure sores at admission, were assessed using the three
      scales by independent assessors within 48 hours of admission, followed by a daily
      monitoring of skin condition for at least 14 days to detect any sore that
      developed. RESULTS: Both the Norton and Waterlow scales had relatively high
      sensitivity (81% and 95%, respectively), whereas the Braden Scale had both high
      sensitivity (91%) and specificity (62%). All three scales had relatively high
      negative predictive values (>90%), but the Braden Scale had better positive
      predictive value. CONCLUSIONS: The Braden Scale is more suitable for use in a
      rehabilitation hospital.

PMID- 9610649
TI  - The relationship between psychological distress and gastrointestinal symptoms in
      women with irritable bowel syndrome.
AB  - BACKGROUND: Individuals with irritable bowel syndrome (IBS) are reported to
      experience more symptoms compatible with psychopathologic disorders, abnormal
      personality traits, and psychological distress. Conversely, individuals with
      psychiatric disorders report higher levels of gastrointestinal (GI) symptoms
      compatible with IBS. Thus, psychological distress may contribute to GI symptoms
      in individuals with IBS. OBJECTIVES: To examine psychological distress in women
      with IBS, women with similar GI symptoms but not diagnosed (IBS nonpatients, IBS
      NP), and asymptomatic Control women. METHODS: The women (N=97) were interviewed,
      completed questionnaires, and maintained daily diaries for 2 months. Across-women
      and within-woman analyses were used to calculate the results. RESULTS: The IBS
      and IBS-NP groups had a higher percentage of lifetime psychopathology and
      recalled psychological distress. At least 40% of the women in the IBS and IBS-NP
      groups had positive relationships between daily psychological distress and daily
      GI symptoms. CONCLUSIONS: Psychological distress is an important component of the
      IBS symptom experience and should be considered when treatment strategies are
      designed.

PMID- 9610650
TI  - Parental sensitivity to infants and toddlers in dual-earner and single-earner
      families.
AB  - BACKGROUND: Concerns have been raised about the effects of maternal employment on
      parent-child relations. Some researchers have concluded that maternal employment
      status has no effect on children's maternal attachments; others have found that
      full-time employment initiated in the first year of life is associated with
      insecure patterns of attachment behavior. The evidence suggests that dual-earner
      parents who have young children have increased psychological distress, affecting
      marital quality and spousal and parenting behaviors. OBJECTIVES: To learn whether
      parental sensitivity and the determinants of parental sensitivity differ for
      first-time parents in single-earner and dual-earner families when their first
      born children are 3 months of age and when they are 2 1/2 years old; and to learn
      the extent to which changes in parental sensitivity and the determinants of
      parental sensitivity differ for single-earner and dual-earner parents during the
      study interval. METHOD: This panel study compared marital quality, psychological
      well-being, and parental sensitivity of single-earner and dual-earner parents
      when their first-born children were 3 months of age and again when they were 2
      1/2 years of age. RESULTS: Employed mothers were more sensitive to their 3-month
      olds than were nonemployed mothers. When children were 2 1/2 years of age, dual
      earner parents had lower marital quality than single-earner parents. Marital
      quality was positively associated with parental sensitivity at both study phases.
      Regardless of maternal employment status, parents' marital quality declined
      during the study interval. CONCLUSIONS: Regardless of mothers' employment status,
      well-educated, middle-class parents tend to provide sensitive parenting. Marital
      quality and psychological well-being are important supports of sensitive
      parenting for dual-earner and single-earner families.

PMID- 9610651
TI  - Cardiovascular dysautonomia of patients with end-stage renal disease and type I
      or type II diabetes.
AB  - BACKGROUND: End-stage renal disease and diabetes mellitus are known to cause
      autonomic dysfunctions that are responsible for poor outcomes. Studies suggest
      that 24-hour heart rate variability with power spectral analysis is more
      sensitive to early changes in autonomic function than laboratory-evoked measures.
      OBJECTIVES: To evaluate cardiovascular autonomic function in patients (a)
      awaiting kidney or pancreas-kidney transplantation, (b) without diabetes (NonDM),
      (c) with Type I insulin dependent diabetes mellitus (IDDM), and (d) with Type II
      noninsulin dependent diabetes mellitus (NIDDM), and to compare the results of the
      laboratory-evoked cardiovascular autonomic tests with those from 24-hour heart
      rate variability monitoring with power spectral analysis. METHOD: This cross
      sectional study examined autonomic function in prekidney transplant patients with
      and without diabetes (N=96), comparing laboratory-evoked measures to 24-hour
      measures. RESULTS: The nondiabetic group had a normal change in heart rate with
      deep breathing, Valsalva ratio, and change in systolic blood pressure with tilt.
      Both diabetic groups had poorer values for all measures of heart rate
      variability; demonstrated abnormal changes in heart rate with deep breathing and
      borderline Valsalva ratios; demonstrated a greater decrease in circadian
      rhythmicity; and had lower SDNNS, pNN50s, and rMSSDs than the nondiabetic group.
      CONCLUSIONS: Results showed that 24-hour measures are more sensitive, that
      patients with end-stage renal disease and diabetes regardless of type experience
      significantly poorer function than do patients without diabetes, and that these
      values approach those associated with sudden cardiac death.

PMID- 9610652
TI  - Older adults and exercise: path analysis of self-efficacy related constructs.
AB  - BACKGROUND: Despite the potential benefits of exercise, rates of exercise among
      older adults remain low. Self-efficacy expectation is the strongest correlate of
      exercise behavior or exercise behavior change. OBJECTIVES: To develop and test
      the predictive ability of a model of exercise among older adults. METHOD: The
      model's constructs related to exercise and self-efficacy included outcome
      expectancy, perceived barriers to exercise, perceived health, age, and lifelong
      leisure exercise among adults 65 to 100 years years of age (N=147). Data were
      collected by personal interview and analyzed with path analysis. RESULTS: Self
      efficacy expectation had a strong direct effect on exercise. Outcome expectancy
      contributed little to exercise in the model. Perceived barriers and self-efficacy
      expectation, followed by age, exerted the most total influence on exercise
      scores. CONCLUSIONS: Lifelong leisure exercise exerts its influence on exercise
      through self-efficacy beliefs, further emphasizing the importance of efficacy.
      Also important are perceived barriers to exercise. Further research should
      examine self-efficacy expectations, perceived barriers, and age as predictors of
      exercise among older adults at different stages of health behavior change.

PMID- 9610653
TI  - Metaphor: the language of nursing researchers.

PMID- 9610654
TI  - William Stewart Halsted is alive and well...

PMID- 9610655
TI  - New screening guidelines for colorectal cancer.

PMID- 9610656
TI  - Submucosal gastric cancer with lymph node metastasis.
AB  - BACKGROUND AND OBJECTIVES: The intraoperative assessment of lymph node metastasis
      of gastric cancer remains difficult and the characteristics of recurrence after
      gastrectomy are not well known regarding submucosal cancer. METHODS: We examined
      452 patients with submucosal gastric cancer and compared the clinicopathologic
      features as well as recurrence patterns between the 71 cases with lymph node
      metastasis (group I) and the 381 without it (group II). RESULTS: The mean tumor
      sizes were 44.8 and 33.5 mm, respectively (P < 0.01). The incidences of lymphatic
      invasion and vascular invasion were 91.5% (65/71) and 45.1% (32/71) in group I,
      which were significantly higher than those in group II (36.7 and 14.2%, 140/381
      and 54/381, respectively, P < 0.01). A total of 21 patients (4.6%, 21/452)
      experienced recurrence after undergoing a gastrectomy and hematogenic recurrence
      was the most frequent type of recurrence (2.0%, 9/452). However, in group I,
      lymphatic recurrence was most frequently observed (7.0%, 5/71), and it was more
      frequent than in group II (0.3%, 1/381, P < 0.01). The median intervals between
      gastrectomy and recurrence were 34.5 and 64.0 months in groups I and II,
      respectively (P < 0.05). CONCLUSIONS: The submucosal cancer with larger size,
      lymphatic invasion, and vascular invasion has high risks for lymph node
      metastasis. Furthermore, a strict follow-up for lymphatic as well as hematogenic
      recurrence is important for the patients with node positive submucosal cancer,
      especially within 5 years after operation.

PMID- 9610657
TI  - Prognostic factors of renal cell carcinoma: a multivariate analysis.
AB  - BACKGROUND AND OBJECTIVES: To establish appropriate therapeutic modalities for
      renal cell carcinoma (RCC), informations on the factors affecting prognosis of
      patients are essential. For this purpose, multivariate analysis including a large
      set of variables is necessary. METHODS: Prognostic significance of 14 clinical
      factors and 19 histologic factors including counting of silver-stained nucleolar
      organizer regions (AgNORs) were evaluated in 96 patients. Age of patients ranged
      from 41 to 85 (median 59) yr with a male to female ratio of 4:1. The tumors were
      staged based on the TNM classification as follows: 7 in stage I, 58 in stage II,
      15 in stage III, and 11 in stage IV. RESULTS: The overall and metastasis-free
      survival rates in all patients were 80.1% and 72.7%, respectively. Multivariate
      analysis using Cox's proportional hazards model performed on the factors proved
      to be significant at the univariate analysis. Univariate analysis revealed four
      clinical factors including presence of macroscopic hematuria, symptoms such as
      pain and palpable abdominal mass, anemia, and adjuvant therapy, and nine
      histologic factors, including AgNOR count, to be significant for survival.
      Multivariate analysis showed that anemia, pathological stage, and AgNOR count
      were independent factors for overall survival of patients. The AgNOR count, in
      particular, is the only predictive factor for metastasis-free survival.
      CONCLUSIONS: Among various clinicopathological factors, anemia, pathological
      stage, and AgNOR count are significant prognosticators of RCC. The AgNOR count is
      also predictive factor for metastasis-free survival.

PMID- 9610658
TI  - Immunohistochemical p53 protein status in nonsmall cell lung cancer is a
      promising indicator in determining in vitro chemosensitivity to some anticancer
      drugs.
AB  - BACKGROUND AND OBJECTIVES: The tumor suppressor oncogene p53 abnormalities have
      been closely associated with resistance or sensitivity of cancer cells to some
      chemotherapeutic agents. We examined the association between p53 protein status
      in nonsmall cell lung cancer (NSCLC) and in vitro chemosensitivity to several
      chemotherapeutic agents. METHODS: Using 146 surgically resected specimens of
      NSCLC, p53 status was immunohistochemically evaluated, and in vitro
      chemosensitivity to 5-fluorouracil (5-Fu), cisplatin (CDDP), mitomycin C (MMC),
      etoposide (VP-16), doxorubicin hydrochloride (ADM), and vindesine sulfate (VDS)
      was examined by a collagen gel-droplet embedded culture drug sensitivity test (CD
      DST, Int J Oncol, 1997;11:449). RESULTS: Sixty-five of 146 materials (45%) showed
      immunohistochemically abnormal p53 protein accumulation in >10% of cancer cells
      within the tumor tissue, being regarded as p53+, whereas 81 (55%) were to p53-,
      in which no or less than 10% positive immunostaining cancer cells were detected.
      By CD-DST, the incidence of chemosensitive, borderline, and resistant p53-
      materials (N=81) to 5-Fu was 37%(N=30), 14%(N=11), and 49%(N=40), whereas that of
      p53+ materials (N=65) was 20%(N=13), 6%(N=4), and 74%(N=48), respectively,
      showing that p53- materials were significantly more sensitive to 5-Fu than p53+
      materials (P=0.011), especially in the adenocarcinoma type. As similar borderline
      association between p53 protein status and in vitro chemosensitivity was also
      shown in ADM (P=0.078), but not in other chemoagents. CONCLUSIONS:
      Immunohistochemically detected p53 protein status in NSCLC patients may be a
      promising indicator in determining in vitro chemosensitivity to some anticancer
      drugs, especially 5-Fu and ADM.

PMID- 9610659
TI  - Different distributions of immunoreactive S100-alpha and S100-beta protein
      expression in human breast cancer.
AB  - BACKGROUND AND OBJECTIVES: Although the localization of S100 protein in breast
      carcinoma has previously been studied, the immunohistochemical expression of the
      S100-alpha and -beta subunits has not been examined. METHODS: Immunohistochemical
      staining for S100-alpha and S100-beta proteins was performed on 72 benign breast
      lesions and 72 infiltrating ductal carcinoma of the breast. Noncross-reactive
      anti-S100-alpha and anti-S100-beta antibodies purified by affinity chromatography
      were used in the studies. RESULTS: More than 30% of the epithelial cells
      comprising all the benign lesions were either S100-alpha or S100-beta positive.
      In breast carcinoma cases, however, >30% of malignant cells were S100-alpha
      positive in 70/72 cases (97.2%), whereas the number of S100-beta positive cells
      exceeded 30% in only 3/72 cases (4.0%). CONCLUSIONS: Immunohistochemical staining
      for S 100-alpha and S100-beta proteins may help to differentiate benign
      proliferative breast lesions from breast cancers in difficult cases.

PMID- 9610660
TI  - Retroperitoneal tumors: do the satellite tumors mean something?
AB  - BACKGROUND AND OBJECTIVES: Primary retroperitoneal tumors constitute a rather
      uncommon disease with an incidence of 2 in 100,000. Local recurrence after
      surgical resection is reported between 60% and 90% at 10 yr. The aim of this
      study was to present the problem of satellite tumors around the main tumor mass
      and their possible relation to local recurrence. METHODS: Twenty-nine patients
      with retroperitoneal tumors underwent surgical resection in our department during
      an 8-yr period. We reviewed their records including their preoperative computed
      tomography (CT) scans. RESULTS: Twenty patients had "complete" resections
      requiring seven nephrectomies, four colectomies, two splenectomies, and one
      appendectomy. In nine cases the resection was incomplete because of tumor
      invasion to vital structures. Histopathology revealed that the resected tumors
      were: liposarcomas (12), leiomyosarcomas (4), paragangliomas (5), malignant
      fibrous histiocytomas (3), other sarcomas (3), schwannoma (1), myelolipoma (1),
      and the malignancy grade was I in 6, grade II in 11, and grade III in 12 cases.
      Two patients died within 30 d of the operation. The I year recurrence rate was
      41.4% (12/29) and the total recurrence rate 55.2% (16/29). Survival at 5 yr was
      31% (9/29), whereas the disease-free survival was 20.7% (6/29). Four patients
      required reoperations. In seven cases (24,1%) preoperative CT scans revealed
      small nodular lesions around the main tumor that were removed en bloc and were of
      the same histopathological type as the main tumor. We called these "satellite"
      tumors. All seven patients had local recurrence within 1 yr. CONCLUSIONS: There
      seems to be a close relationship between the finding of satellite tumors and the
      recurrence of the disease. The existence of satellite tumors on the preoperative
      CT scan may be used as a guide for the extent of the resection, and further
      investigations are necessary before they are used as a prognostic sign.

PMID- 9610661
TI  - Spread of colorectal cancer micrometastases in regional lymph nodes by reverse
      transcriptase-polymerase chain reactions for carcinoembryonic antigen and
      cytokeratin 20.
AB  - BACKGROUND AND OBJECTIVES: Lymph node metastasis is known as a significant
      predictor of prognosis in colorectal cancer patients. Recently, reverse
      transcriptase polymerase chain reaction (RT-PCR) has been applied to detecting
      micrometastasis. To assess the risk of recurrence and accurately determine the
      spread of tumor cells, we examined lymph node micrometastases in a series of
      colorectal cancer patients. METHODS: We examined 202 lymph nodes obtained from 13
      colorectal cancer patients who underwent curative operation and were
      histologically diagnosed to be node-negative, using RT-PCR to amplify mRNAs for
      two epithelial markers, carcinoembryonic antigen (CEA) and cytokeratin 20 (CK
      20). RESULTS: All the cases, including early stage patients, had micrometastases.
      A total of 102 among 202 lymph nodes (50.5%) were positive for either CEA or CK
      20, or both (47.0, 40.1, and 36.6% respectively). Positive lymph nodes were
      spread along the courses of vascular trunks as well as being located in more
      distant regions. CONCLUSIONS: Even in histologically negative lymph nodes, there
      is a considerable possibility that micrometastases may exist. Their detection by
      RT-PCR may improve clinical staging and indications for cancer therapy. We should
      also take care in the choice of surgical approach.

PMID- 9610662
TI  - Deep venous thrombosis after orthopedic surgery in adult cancer patients.
AB  - BACKGROUND AND OBJECTIVES: Patients with cancer and patients undergoing major
      orthopedic procedures are two groups at risk of deep venous thrombosis (DVT). The
      objective was to determine the rate of venous thromboembolic disease in patients
      with a malignant neoplasm and major orthopaedic surgery of the lower limb.
      METHODS: The study included 169 patients. All patients were given knee-high
      intermittent pneumatic compression devices for prophylaxis. Postoperative
      surveillance for thrombosis was performed on all patients with venous duplex
      doppler ultrasonography. RESULTS: Proximal DVT occurred in 24 of 169 patients
      (14.2%). One patient (0.6%) developed a symptomatic, nonfatal pulmonary embolus
      (PE). The development of DVT was not associated with age, sex, type of surgery,
      type of neoplasm, location, or pathologic fracture. The addition of anticoagulant
      medication such as warfarin did not significantly reduce the rate of DVT in a
      subset of 54 patients. In three patients, the DVT occurred only in the
      contralateral limb, and in four patients, there were bilateral DVTs. CONCLUSIONS:
      When intermittent compression boots were used for prophylaxis in conjunction with
      ultrasound screening, the risk of proximal DVT was substantial (14.2%), but the
      rate of symptomatic PE was low (0.6%).

PMID- 9610663
TI  - CMF + radiotherapy in the primary treatment of operable breast cancer:
      preliminary results of a phase II pilot study.
AB  - BACKGROUND AND OBJECTIVES: Chemotherapy and radiotherapy have been investigated
      in several studies about their role in primary (neoadjuvant) treatment before
      surgery in breast cancer. We proposed a pilot study to evaluate a primary scheme
      of alternate radio-chemotherapy in the treatment of operable (T2- small T3)
      breast cancer. METHODS: 14 patients were recruited. Cyclophosphamide,
      methotrexate, and 5-fluorouracil (CMF) were administered on days 1 and 8, every 4
      wk, for two cycles. Radiotherapy was administered during the 3rd and 4th wk (5
      d/wk) after the beginning of chemotherapy. The patients were operated on within
      24 wk. All the patients received four additional cycles of chemotherapy within 1
      mo after surgery. RESULTS: We observed: 1 (8.3%) complete remission (CR), 8
      (66.7%) partial remission (PR), 3 (25%) stationary disease (SD); no progressive
      disease was observed. Modified radical mastectomy was performed on 7 patients
      (58.3%). Conservative surgery was performed on 5 cases (41.7%). No major
      complications were observed. No patient has shown local or distant recurrence.
      CONCLUSIONS: This study shows the feasibility of a primary chemoradiotherapy
      treatment for breast cancer. But to evaluate the impact of this therapy on
      overall survival and recurrence risk and its possible introduction in clinical
      practice, we need larger series and longer follow-up.

PMID- 9610664
TI  - Priapism secondary to penile metastasis: a report of two cases and a review of
      the literature.
AB  - Malignancy metastasis to the penis is an uncommon clinicopathological entity. We
      present two cases of malignant priapism following penile metastasis, in which the
      diagnosis was established by core needle biopsy of the corpus cavernosum. Primary
      tumors were urothelial carcinoma of the urinary bladder in one case (the patient
      having concomitant high-grade prostatic adenocarcinoma) and prostatic
      adenocarcinoma in the other. The clinicopathological features of 51 previously
      reported cases of penile metastasis in the recent literature are reviewed.

PMID- 9610665
TI  - Strip biopsy for gastrointestinal carcinoid tumor.

PMID- 9610666
TI  - Statistical inaccuracies in a comparative analysis of imaging modalities in the
      assessment of nodal metastasis in esophageal cancer.

PMID- 9610667
TI  - Perspectives of neuroimmune issues and substances of abuse.

PMID- 9610668
TI  - Opiates and infection.
AB  - This review on the effects of opiate use on infectious diseases discusses the
      complete spectrum of infections in the opiate user, including those of the lung,
      the GI tract, the skin, the skeletal system, and the CNS. There is both increased
      prevalence and increased severity of bacterial and viral infections in injection
      drug users with the outcome of increased morbidity and mortality. The
      experimental administration of opiates has lead to a greater understanding of the
      effects on susceptibility to and progression of infectious diseases. Animal
      models of opiate dependence and infection are reviewed with specific attention to
      cases in which the opiate-mediated effects are harmful and in which cases they
      are beneficial.

PMID- 9610669
TI  - Evidence for central opioid receptors in the immunomodulatory effects of
      morphine: review of potential mechanism(s) of action.
AB  - This review will discuss studies demonstrating that activation of opioid
      receptors within the central nervous system alters various immune system
      parameters. Specifically, natural killer cell cytolytic activity and lymphocyte
      proliferative responses to mitogen appear to be modulated predominantly, if not
      exclusively, through central opioid receptors. The potential mechanisms by which
      central opioid receptors appear to modulate these peripheral immune functions
      will be examined by evaluating the role of both the hypothalamic-pituitary
      adrenal (HPA) axis and the autonomic nervous system. The studies discussed below
      indicate that acute administration of morphine or related compounds appears to
      primarily alter peripheral immune function through the sympathetic nervous
      system, while more prolonged exposure to opioids alter the immune system
      predominantly by activation of the HPA axis. Finally, the potential clinical
      relevance of these observations are discussed in relationship to both the
      therapeutic use, as well as the abuse of opioid compounds.

PMID- 9610670
TI  - Opioid mediated effects on the immune system: sympathetic nervous system
      involvement.
AB  - Opioids have been hypothesized to suppress parameters of immune function by
      acting within the central nervous system to increase the activity of the
      hypothalamic-pituitary-adrenal axis and the sympathetic nervous system.
      Production of catecholamines and adrenocorticoids have been demonstrated to be
      responsible for many of the observed immunomodulatory effects which occur
      following opioid administration. In general, the sympathetic nervous system has
      been shown to play a role in regulating lymphocyte proliferation and natural
      killer cell activity as well as several other parameters of immune function.
      Here, we will focus primarily on the role of the sympathetic nervous system in
      modulating opioid induced immunosuppression. The role of the hypothalamic
      pituitary adrenal axis is reviewed elsewhere in this issue.

PMID- 9610671
TI  - Opioid modulation of immune responses: effects on phagocyte and lymphoid cell
      populations.
AB  - The literature describing effects of morphine on cells of the immune system
      points to the clear conclusion that morphine given in vivo suppresses a variety
      of immune responses that involve the major cell types in the immune system,
      including natural killer (NK) cells, T cells, B cells, macrophages and
      polymorphonuclear leukocytes (PMNs). Depression of NK cell activity has been
      reported in humans, monkeys and rodents. Similarly, responses of T cells are
      depressed by morphine, as assessed by inhibition of induction of delayed-type
      hypersensitivity reactions and cytotoxic T-cell activity, modulation of T-cell
      antigen expression, and depression of responses to T-cell mitogens. Effects on T
      cells have been reported in humans, monkeys and rodents. Effects of morphine on B
      cell activity have mainly been tested in rodents using assays of antibody
      formation, which also require macrophages and T cells, preventing a conclusion as
      to the cell type being affected. Consistent effects on phagocytic cell function
      have been reported in rodents given morphine. In contrast, studies on
      immunomodulatory effects of morphine added to cells of the immune system in vitro
      have shown robust effects on some of these cell types, but not others. There is a
      rich literature demonstrating downregulation of phagocytic cell function by
      morphine, particularly for human peripheral blood mononuclear cells (PBMCs) and
      PMNs. Phagocytosis, chemotactic responses, interleukin production, and generation
      of activated oxygen intermediates and arachidonic acid products have all been
      reported to be inhibited. On the contrary, the literature does not support direct
      effects of morphine on NK cell function, is inconclusive concerning effects on B
      cells, and provides limited evidence for effects on T cells. The divergence
      between the in vivo and in vitro data suggests that effects on some cells in the
      immune system observed after in vivo morphine are probably not direct, but
      mediated. In aggregate, the literature supports the existence of an in vivo
      neural-immune circuit through which morphine acts to depress the function of all
      cells of the immune system. Further, there is strong evidence that morphine can
      directly depress the function of macrophages and PMNs, and modulate expression of
      one type of T-cell surface marker. There is, however, little evidence for direct
      effects of morphine on NK cells and B cells. A further complication emerges from
      reports of immunopotentiation of immune function in in vitro assays using
      endogenous opioids. The possibility of different receptors for endogenous and
      exogenous opioids or of interactions among the activated opioid receptors may
      account for these opposing effects.

PMID- 9610672
TI  - Evidence for opioid receptors on cells involved in host defense and the immune
      system.
AB  - Although the role of opiates and opioids in the physiological and pathological
      function of the immune system is only beginning to be unraveled, converging lines
      of evidence indicate that the opioid receptors expressed by immune cells are
      often the same or similar to the neuronal subtypes, particularly delta and kappa.
      Recent studies also point to the existence of novel opioid receptors and/or
      binding sites on immune cells that are selective for morphine. Opioids and their
      receptors, particularly those with high affinity for delta agonists, appear to
      function in an autocrine/paracrine manner. Thus, opioid peptides generated from
      immune-derived proenkephalin A act as cytokines, capable of regulating myriad
      functions of both granulocytes and mononuclear cells. Further identification and
      characterization of receptors and signal transduction pathways that account for
      some of the unique properties of opiate binding and immunomodulation (e.g., dose
      dependent effects of morphine that occur at exceptionally low concentrations
      relative to the Kd's of the neuronal mu receptor or the morphine binding site
      reported on activated human T-cells) represents one of the major research
      challenges ahead. Elucidating mechanisms, such as these, may provide unique
      therapeutic opportunities through the application of opioid immunopharmacology to
      disorders involving immune responses in peripheral organs and the central nervous
      system.

PMID- 9610673
TI  - Opiate binding sites in the cellular immune system: expression and regulation.
AB  - The direct actions of opiates on the mammalian immune system depend on the
      existence of ligand binding sites either on the surface of the affected cell or
      in the interior of the cell. With the cloning of various opiate receptors from
      neuronal tissue, numerous researchers have screened leukocyte cDNA libraries for
      the expression of these receptors with some positive results. However, the
      pattern of expression of neuronal opiate receptors in the cellular immune system
      does not completely explain the biological action of opiates there. Several
      possibilities could account for this non-congruence including differential
      expression of the receptors as determined by such factors as cell population or
      prior history of the cells; the existence of sequence modified versions of the
      neuronal receptors such that the amplification methods miss their presence; or
      the opiates act by a different, non-receptor mechanism in the cellular immune
      system.

PMID- 9610674
TI  - The opioid-cytokine connection.
AB  - Opioids (exogenous opiates and endogenous opioid peptides) have a diversity of
      effects on the immune system. Although numerous studies have shown that opioid
      induced immunosuppression can be mediated indirectly via the central nervous
      system (CNS) or through direct interactions with immunocytes, the precise
      cellular mechanisms underlying the immunomodulatory effects of opioids are
      largely unknown. In recent years, investigations from several laboratories have
      indicated that opioids can operate as cytokines, the principal communication
      signals of the immune system. All of the major properties of cytokines are shared
      by opioids, i.e., production by immune cells with paracrine, autocrine, and
      endocrine sites of action, functional redundancy, pleiotropy and effects that are
      both dose- and time-dependent. Studies of the effects of opioids on peripheral
      blood mononuclear cells (PBMC) or brain cells cocultured with HIV-infected cells
      suggest that some of the immunoregulatory actions of opioids are mediated by
      ultrahigh affinity receptors on PBMC and glial cells. Because the CNS is
      populated predominantly by astroglia and microglia which have properties of
      immune cells, it is possible that certain of the CNS effects of opioids involve
      cytokine-like interactions with glial cells. Although there is mounting evidence
      supporting the concept that opioids are members of the cytokine family, the
      relative contribution of the opioids to immunoregulation remains unclear. The
      importance of opiate addiction in the AIDS epidemic means that gaining a better
      understanding of the mechanisms of opioid-induced immunomodulation is of more
      than academic interest.

PMID- 9610675
TI  - Autoimmunovascular regulation: morphine and anandamide and ancondamide stimulated
      nitric oxide release.
AB  - The hypothesis concerning morphine as an endogenous signal molecule has been
      strengthened with the recent discovery of a new opiate receptor subtype,
      designated mu3. This opiate receptor is opiate alkaloid sensitive and opioid
      peptide insensitive, including peptides previously shown to have affinities for
      mu opiate receptors. This receptor is coupled to nitric oxide release in human
      endothelial cells, granulocytes and monocytes and in invertebrate immunocytes and
      microglia. In relation to the endothelium, it has also been coupled to
      vasodilation via nitric oxide. Given the known influence of nitric oxide in
      downregulating cell adhesion, the role of this compound has now been investigated
      in also diminishing endothelial-immunocyte interaction. Morphine, via nitric
      oxide, has the potential to diminish adhesion molecule expression and in so doing
      calm an inflammatory process between immunocytes and the endothelial surface. In
      this regard, the potential for abuse is also present.

PMID- 9610676
TI  - Opiates as potential cofactors in progression of HIV-1 infections to AIDS.
AB  - Because of the widely documented association of AIDS with opiate abuse, there is
      considerable interest in knowing whether opiates alter progression of HIV-1
      infections to AIDS. The main reason for this interest is that opiates and opiate
      abuse have been shown to have broad influence on immune processes as well as in
      vitro expressions of HIV-1. This article reviews literature defining the
      connection between opiate use and AIDS. Basic understanding of the effects of
      opiates on immune process and HIV-1 infection, especially as derived from study
      of a monkey model of AIDS, are discussed as well as epidemiological data
      regarding the connection between chronic injected drug abuse and AIDS, in the
      context of current knowledge about the HIV-1 infectious process and AIDS
      pathogenesis. Theoretically, there is ample reason to suspect that opiates are
      involved in progression of HIV-1 infections to AIDS. To date, however,
      epidemiological approaches have been unable to link decline in CD4 T-cell counts,
      as a marker of AIDS progression, with opiate use--although other indices of AIDS
      progression have yet to be thoroughly evaluated in this regard. Also, the impact
      of opiate use and abuse on opportunistic infections occurring prior to or
      concurrent with HIV-1 infection has not been closely scrutinized. Interestingly,
      despite considerable evidence delineating the potential of opiates to exacerbate
      HIV-1 infections, there is suggestive evidence from both clinical observations
      and basic studies that homeostatically balancing conditions of chronic,
      consistent opiate exposure have the potential to protect the host from
      progression of HIV-1 infections--a situation that may well differ from when
      opiate-naive subjects first experience exposure to opiates and when opiate
      dependency is not maintained in a consistent fashion. Taken together, therefore,
      information from basic studies, including most particularly studies with monkeys,
      and epidemiological studies, indicates that effects of opiates on progression to
      AIDS may be conditionally variable. There are many aspects of the drug abuse
      culture that have potentially offsetting consequences in terms of their potential
      to up- or down-regulate both HIV-1 expression and host protective responses
      thereto that could be relevant in this regard. In conclusion, many ambiguities
      are yet to be considered, and basic and epidemiological studies to be pursued
      before the opiate-AIDS connection is fully understood.

PMID- 9610677
TI  - Cocaine abuse and HIV-1 infection: epidemiology and neuropathogenesis.
AB  - The epidemiology of cocaine abuse and potential relationships of cocaine
      withdrawal to human immunodeficiency virus type 1 (HIV-1)-associated dementia
      (HAD) are discussed. Neuroendocrinological changes in HIV-1 infection of the
      central nervous system (CNS) are discussed with the relevant impact of cocaine
      abuse. HIV-1 load in the brain tissue of infected substance users is described
      along with possible associations with neuropathology and HAD. Finally, the
      molecular epidemiology and sequence heterogeneity of HIV-1 and their implications
      for neuropathogenesis are summarized. The complex context of addressing cocaine
      abuse in the setting of HIV-1 infection appears more tractable when decomposed
      into its components.

PMID- 9610678
TI  - Marijuana, immunity and infection.
AB  - The influence of marijuana cannabinoids on immune function has been examined
      extensively over the last 25 yr. Various experimental models have been used
      employing drug-abusing human subjects, experimental animals exposed to marijuana
      smoke or injected with cannabinoids, and in vitro models employing immune cell
      cultures treated with various cannabinoids. For the most part, these studies
      suggest that cannabinoids modulate the function of T and B lymphocytes as well as
      NK cells and macrophages. In addition to studies examining cannabinoid effects on
      immune cell function, other reports have documented that these substances
      modulate host resistance to various infectious agents. Viruses such as herpes
      simplex virus and murine retrovirus have been studied as well as bacterial agents
      such as members of the genera Staphylococcus, Listeria, Treponema, and
      Legionella. These studies suggest that cannabinoids modulate host resistance,
      especially the secondary immune response. Finally, a third major area of host
      immunity and cannabinoids is that involving drug effects on the cytokine network.
      Employing in vivo and in vitro models, it has been determined that cannabinoids
      modulate the production and function of acute phase and immune cytokines as well
      as modulate the activity of network cells such as macrophages and T helper cells,
      Th1 and Th2. These results are intriguing and demonstrate that under certain
      conditions, cannabinoids can be immunomodulatory and enhance the disease process.
      However, more studies are needed to determine both the health risk of marijuana
      abuse and the role of the cannabinoid receptor/ligand system in immune regulation
      and homeostasis.

PMID- 9610679
TI  - Drugs and immunity: cannabinoids and their role in decreased resistance to
      infectious disease.
AB  - Marijuana, Cannabis sativa, elicits a variety of effects in experimental animals
      and humans. Delta-9-tetrahydrocannabinol (THC) is the major psychoactive
      component in marijuana. This substance has been shown, also, to be
      immunosuppressive and to decrease host resistance to bacterial, protozoan, and
      viral infections. Macrophages, T lymphocytes, and natural killer cells appear to
      be major targets of the immunosuppressive effects of THC. Definitive data which
      directly link marijuana use to increased susceptibility to infection in humans
      currently is unavailable. However, cumulative reports indicating that THC alters
      resistance to infection in vitro and in a variety of experimental animals support
      the hypothesis that a similar effect occurs in humans.

PMID- 9610680
TI  - Regulation of the cAMP cascade, gene expression and immune function by
      cannabinoid receptors.
AB  - The objective of this article is to discuss the putative role of cannabinoid
      receptors in immune modulation by cannabinoid compounds. The primary focus is on
      the signal transduction events that are initiated following ligand binding to
      cannabinoid receptors and how these events lead to detrimental effects on the
      normal responsiveness of immunocompetent cells. Toward this end, signalling
      events are traced from the cannabinoid receptor to the transcription factors
      which are adversely regulated in the presence of cannabinoid compounds during
      leukocyte activation. Moreover, this aberrant regulation of transcription factors
      is discussed in the context of altered gene expression and the impact this has on
      leukocyte function. Lastly, an important goal of this article is to dispel a long
      standing myth that the cyclic adenosine 3':5'-monophosphate (cAMP) cascade is a
      negative regulatory pathway for immunocompetent cells. This chapter examines two
      major immunologic cell-types which are well established as exhibiting altered
      function following cannabinoid treatment, helper T-cells and the macrophage. Not
      discussed are the effects of cannabinoids on B-cell function. This is primarily
      due to the rather refractory nature of B-cells to inhibition by cannabinoids in
      spite of the fact that this cell-type expresses functional cannabinoid receptors
      [Schatz, A.R., Koh, W.S., Kaminski, N.E., 1993. Delta9-tetrahydrocannabinol
      selectively inhibits T-cell dependent humoral immune responses through direct
      inhibition of accessory T-cell function. Immunopharmacol., 26, pp. 129-137.]. One
      cautionary note, although the focus of this article is on cannabinoid receptor
      mediated signalling events, immune modulation by cannabinoid compounds is likely
      multi-factorial presumably involving receptor as well as receptor-nonrelated
      events. Effects on leukocytes by cannabinoids which are believed to be mediated
      by receptor-nonrelated events are outside the scope of this paper and will not be
      discussed. One last introductory point is that even though their is presumably
      little overlap in the genes which are regulated by cannabinoids in leukocytes as
      compared to other cell-types (e.g., neural cells), the major signalling pathways
      involved in cellular regulation are ubiquitous. With that in mind, it is likely
      that their is a considerable amount of similarity in the signalling pathways
      regulated by cannabinoids in cell-types of different lineage, given that they
      express cannabinoid receptors. In this context, signalling events observed in
      leukocytes can provide important insight into which genes may be modulated by
      cannabinoid in other cell types.

PMID- 9610681
TI  - Acute and chronic effects of cocaine on the immune system and the possible link
      to AIDS.
AB  - The pathogenesis of AIDS is a complex and prolonged process that is affected by a
      variety of cofactors, including the abuse of both intravenous and smoked (crack)
      cocaine. The exact mechanisms by which cocaine facilitates this disease are yet
      to be proven, but likely include a combination of increased risk due to cocaine
      related social behaviours, a wide-ranging capacity for cocaine to suppress the
      immune system, and an effect of cocaine on the infectivity and replication of
      HIV. While sometimes contradictory, both human and animal studies document that
      cocaine alters the function of natural killer (NK) cells, T cells, neutrophils
      and macrophages, and alters the ability of these cells to secrete
      immunoregulatory cytokines. In addition to these effects on the immune system,
      cocaine also enhances the infectivity and/or replication of HIV when tested using
      human cells in vitro.

PMID- 9610682
TI  - In vivo effects of cocaine on immune cell function.
AB  - Cocaine use has been shown to increase the risk of HIV infection in humans, and
      this increased risk cannot be explained by i.v. drug use alone. It is thought
      that this increased susceptibility may be a result of decreased immune
      responsiveness in cocaine addicts. Scientists are now using animal models to
      study the effects of cocaine on immune function in vivo under controlled
      conditions. Many facets of the immune system are being examined, which include
      immune cell number and distribution, cellular- and humoral-mediated immunity,
      cytokine production, and immunocompetence to challenges such as infection and
      tumor growth. The effects of cocaine on many of these functions are not yet
      clear. Often there are variations in the response of the immune system to
      cocaine. Potential confounding factors include variations in dose, duration of
      treatment, and route of administration of cocaine, as well as variations in assay
      protocols. In addition, there appear to be species differences in immune
      responses to cocaine. Although it is clear that more research is necessary to
      resolve the discrepancies, a sufficient number of trends are starting to emerge.
      This review will systematically evaluate the reported effects of cocaine on
      immune cell function in vivo. In addition, the possible mechanisms that may be
      contributing to the immune modulation observed with cocaine in vivo will be
      addressed. Further, data will be presented describing the effects of cocaine on
      the autonomic nervous system and the neuroendocrine system suggesting that
      inhibition of serotonin uptake may be an important component of the overall
      effects of cocaine on the immune system.

PMID- 9610683
TI  - Immunomodulatory effects of cigarette smoke.
AB  - Cigarette smoke is a major health risk factor which significantly increases the
      incidence of diseases including lung cancer and respiratory infections. This
      increased susceptibility may result from cigarette smoke-induced impairment of
      the immune system. While the acute effects of cigarette smoke on the immune
      system are less clear, chronic exposure to cigarette smoke or nicotine causes T
      cell unresponsiveness. This apparent T cell anergy may account for or contribute
      to the immunosuppressive and anti-inflammatory properties of cigarette
      smoke/nicotine. Nicotine-induced immunosuppression may result from its direct
      effects on lymphocytes, indirectly through its effects on the neuroendocrine
      system, or both.

PMID- 9610684
TI  - Immunomodulation by nitrite inhalants may predispose abusers to AIDS and Kaposi's
      sarcoma.
AB  - Epidemiological studies indicating that nitrite inhalant abuse is a co-factor in
      HIV infection and in Kaposi's sarcoma are supported by recent experimental
      studies, described in this review. Inhalation exposure to the nitrites produce a
      nonspecific cytotoxicity, depleting many cells of the immune system. Apparently
      distinct from this cytotoxicity, inhalation of the nitrites impairs a variety of
      immune mechanisms, affecting both humoral and cell-mediated immunity. In
      addition, the inhalant-increased macrophage production of the inflammatory
      cytokine tumor necrosis factor-alpha (TNF-alpha), can directly stimulate HIV
      replication and can also stimulate the growth of Kaposi's sarcoma cells. Thus,
      nitrite inhalants may impair immune resistance to infection and actively promote
      viral replication and tumor growth.

PMID- 9610685
TI  - Potential for the effects of anabolic steroid abuse in the immune and
      neuroendocrine axis.
AB  - Some of the effects that high-dose anabolic steroid abuse have and could have on
      the interactions between the immune and neuroendocrine systems are reviewed.
      Considering the past demonstrations on the actions of normal steroids on
      endocrine and immune responses, it is apparent that pharmacologically high doses
      of both normal and derivatized androgens (anabolic steroids) could have a
      significant effect. Indeed, some of the pathologies attributed to anabolic
      steroid abuse point to disturbances in the intimate connection between
      neuroendocrine and immune function and interaction. We attempt to review both the
      direct and indirect effects of this abuse, not only on this interaction but also
      on certain immune functions in particular.

PMID- 9610686
TI  - Fibrosarcoma: a historic commentary.

PMID- 9610687
TI  - Tamoxifen and breast conservation: do we still need radiotherapy?

PMID- 9610688
TI  - Current clinical trial design issues in hormone-refractory prostate carcinoma.
      Consensus Panel.

PMID- 9610689
TI  - Monoclonal origin of an esophageal carcinosarcoma producing granulocyte-colony
      stimulating factor: a case report.
AB  - BACKGROUND: Carcinosarcomas are comprised of carcinomatous and sarcomatous
      elements, and their histogenesis remains unclear. The authors examined the serum
      concentrations of hematopoietic growth factors and performed immunohistochemical
      studies on an esophageal carcinosarcoma from a patient with marked granulocytosis
      to determine its histopathogenesis and clonality. METHODS: The authors examined
      the case of a 63-year-old man with a polypoid tumor of the esophagus associated
      with marked leukocytosis (131 x 10(9) per liter). Immunohistochemical staining of
      the esophageal tumor was performed using monoclonal antibodies against
      granulocyte-colony stimulating factor (G-CSF), keratin, epithelial membrane
      antigen (EMA), and vimentin. RESULTS: The patient's leukocyte count was increased
      (124 x 10(9) per liter) on admission. Because mature granulocytes predominantly
      were increased despite the absence of apparent infection, the patient's serum G
      CSF concentration was examined and found to be 286.0 pg/mL and to increase with
      time. After thoracic esophagectomy was performed, granulocyte count and serum G
      CSF concentration rapidly normalized. G-CSF concentration was 50-fold higher in
      the tumor tissue extract than in the extract from normal esophageal tissue.
      Microscopic examination of the resected specimens revealed that the tumor was
      comprised of squamous cell carcinoma (SCC) and spindle-shaped sarcomatous
      elements, and transitional features were observed within these two components.
      Immunohistochemical examination disclosed cells that were positive for keratin
      and EMA in the carcinomatous element and vimentin positive cells in the
      sarcomatous element. However, both types of tumor cells were positive for G-CSF.
      CONCLUSIONS: The presence of G-CSF in both SCC cells and spindle-shaped
      sarcomatous cells indicated that these two components originated from a single
      clone.

PMID- 9610690
TI  - The relation between the growth patterns of gastric carcinoma and the expression
      of hepatocyte growth factor receptor (c-met), autocrine motility factor receptor,
      and urokinase-type plasminogen activator receptor.
AB  - BACKGROUND: Hepatocyte growth factor receptor (c-met), autocrine motility factor
      receptor (AMFR), and urokinase-type plasminogen activator receptor (uPAR) are
      known to play important roles in tumor cell migration, invasion, and metastasis.
      The authors studied the relation between the expression patterns of these genes
      and the growth patterns of human gastric carcinoma. METHODS: The relation between
      the expression of c-met, AMFR, and uPAR and clinicopathologic parameters was
      studied using immunohistochemical preparations from 102 paraffin embedded primary
      gastric carcinomas. RESULTS: Of 102 cases, 43 (42%) had overexpression of c-met,
      and AMFR and uPAR immunoreactivity was observed in 41 cases (40%) and 38 cases
      (37%), respectively. Macroscopic examination revealed that all three genes were
      expressed in 1 (3%) of 32 early stage gastric carcinomas, 0 (0%) of 29 localized
      carcinomas (Borrmann types 1 and 2), and 16 (39%) of 41 infiltrating carcinomas
      (Borrmann types 3 and 4). In particular, the incidence (68%, 13 of 19 cases) of
      simultaneous expression of the three genes was significantly higher in Borrmann
      type 4 gastric carcinoma than in the other macroscopic types (P < 0.01). The
      overexpression of these genes was also closely associated with lymph node
      metastasis and peritoneal dissemination. In addition, the simultaneous
      overexpression of the three genes was associated with positive lymphatic vessel
      invasion and infiltrating type. Patients with tumors that simultaneously
      expressed all three genes had significantly poorer prognoses than those with
      tumors expressing only one or two of the genes. Furthermore, the number of genes
      expressed was closely related to the prognosis, and the Cox proportional hazards
      model identified this as one of the independent prognostic factors. CONCLUSIONS:
      These results suggest that the expression patterns of c-met, AMFR, and uPAR may
      be closely associated with the progression and invasion of gastric carcinoma as
      well as the prognoses of the patients. Borrmann type 4 gastric carcinoma is
      characterized by the diverse and simultaneous expression of these three genes.

PMID- 9610691
TI  - Comorbidity and age as predictors of risk for early mortality of male and female
      colon carcinoma patients: a population-based study.
AB  - BACKGROUND: Colon carcinoma primarily affects persons 65 years and older. Seventy
      five percent of the incident tumors affect persons in this age group. Because of
      their advanced age, older patients already may be coping with other concomitant
      major physical illnesses. This article documents preexisting diseases in older
      colon carcinoma patients at diagnosis and evaluates the effects of their
      comorbidity burden on early mortality. METHODS: Prevalence of comorbid conditions
      was assessed by a retrospective medical records review of an age-stratified
      random sample of male and female patients aged 55-64 years, 65-74 years, and 75+
      years (males, n=799; females, n=811). Data were collected on comorbidity by the
      National Institute on Aging (NIA) and National Cancer Institute (NCI) and merged
      with NCI Surveillance, Epidemiology, and End Results (SEER) tumor registry data.
      RESULTS: Hypertension, high impact heart conditions, gastrointestinal problems,
      arthritis, and chronic obstructive pulmonary disease emerged as the most
      prominent comorbid conditions in the NIA/NCI SEER Study sample. The prevalence of
      comorbidity in the number and type of conditions was similar for both men and
      women (e.g., 40% of each gender had > or = 5 comorbidities). Within 2 years of
      diagnosis, 28% (n=454) of the patients had died. The number of comorbid
      conditions was significant in predicting early mortality in a model including
      age, gender, and disease stage (P=0.0007). Certain comorbidities, classified as
      "current problem," added significantly to a basic model (e.g., heart problems,
      alcohol abuse, liver disease, and deep vein thrombosis). CONCLUSIONS: Although
      disease stage at time of diagnosis of colon carcinoma is a crucial determinant of
      patient outcome, comorbidity increases the complexity of cancer management and
      affects survival duration. Cancer control and treatment research questions should
      address comorbidity issues pertinent to the age group primarily afflicted with
      colon carcinoma (i.e., the elderly).

PMID- 9610692
TI  - GIVIO-SITAC 01: A randomized trial of adjuvant 5-fluorouracil and folinic acid
      administered to patients with colon carcinoma--long term results and evaluation
      of the indicators of health-related quality of life. Gruppo Italiano Valutazione
      Interventi in Oncologia. Studio Italiano Terapia Adiuvante Colon.
AB  - BACKGROUND: In 1989, the authors began a randomized trial to determine whether 5
      fluorouracil and high dose folinic acid (HD-FUFA) would increase the event free
      and overall survival of patients with resectable Dukes B and C (AJCC/UICC Stage
      II and Stage III) colon carcinoma, and to assess the toxicity of the treatment
      and its impact on selected health-related quality-of-life indicators. Early
      results were published as a part of an international multicenter pooled analysis
      (IMPACT) in 1995. The purpose of this report is to update the survival data for
      patients enrolled in the trial and describe their reported perceptions of their
      own health and quality of life. METHODS: The trial involved multiple treatment
      centers, with a centralized randomization between surgery alone and surgery with
      chemotherapy. The HD-FUFA regimen employed consisted of 5-fluorouracil (370
      mg/m2) plus folinic acid (200 mg/m2) administered daily for 5 days every 4 weeks
      for 6 cycles. Patients' perceptions of their own health status were obtained by
      means of 3 self-administered questionnaires, which were completed by patients at
      the time of discharge from the treatment center and at 6 and 24 months after
      randomization. RESULTS: Overall, 888 patients with resected Dukes B2 and C colon
      carcinoma were enrolled in the trial. HD-FUFA significantly reduced mortality by
      25% (95% confidence interval, 5-41%; P=0.02) and events by 31% (95% confidence
      interval, 14-45%; P < or = 0.001). Compliance with treatment was good; more than
      80% of patients completed the planned therapy. Toxicity was mild, and oral
      mucositis was the main side effect. None of the health-related quality-of-life
      parameters investigated (emotional status, worry about the future, changes in
      social life, impact of the disease, follow-up, and global quality of life) seemed
      to be affected by the treatment to which patients were allocated. A positive
      trend in the evolution of patients' psychologic status was observed. CONCLUSIONS:
      Long term results of this SITAC study confirm that HD-FUFA is a well-tolerated,
      effective 6-month adjuvant regimen for patients with colon carcinoma that has no
      detrimental effect on their quality of life.

PMID- 9610693
TI  - Minute nodular intrahepatic cholangiocarcinoma.
AB  - BACKGROUND: This study describes the clinicopathologic features of minute
      intrahepatic cholangiocarcinoma (ICC) and clarifies the relation between minute
      nodular ICC and hepatitis viral infection. METHODS: The presence of hepatitis C
      virus antibody (anti-HCV) and hepatitis B surface antigen (HBsAg) was examined in
      the serum of 50 patients with ICC who underwent hepatectomy from 1990-1996. The
      ICCs included 12 minute tumors (<3 cm in greatest dimension), 6 of which were
      nodular type and 6 others were nonnodular type (5 of periductal spreading or
      infiltrating type and 1 of intraductal type). RESULTS: Of these 50 patients with
      ICC, 16 (32%) were positive for anti-HCV, 5 (10%) were positive for HBsAg, and 1
      (2%) was positive for both. The prevalence of hepatitis viral infection in cases
      of minute nodular-type tumor (83%; 5 patients positive for anti-HCV) was
      significantly higher than that in cases of minute nonnodular-type tumor (0%; P <
      0.05). These minute nodular-type tumors were detected during follow-up of
      patients with chronic hepatitis or cirrhosis. All patients were treated with
      hepatectomy alone. At last follow-up, 3 patients had been free of disease for >5
      years after surgery. However, 1 patient died 2 years after surgery because of
      remnant liver and lymph node recurrence. CONCLUSIONS: Minute nodular ICC appears
      to be related to hepatitis viral infection and could be detected at an early
      stage, similar to hepatocellular carcinoma, by following up cases of chronic
      hepatitis or cirrhosis.

PMID- 9610694
TI  - A clinicopathologic and immunohistochemical study of ten pancreatic lymphangiomas
      and a review of the literature.
AB  - BACKGROUND: Pancreatic lymphangiomas are rare benign tumors, of which only a few
      cases have been reported in the literature. In this study, the authors present a
      series of primary pancreatic lymphangiomas. METHODS: Cases of nonepithelial
      pancreatic cystic tumors (lymphangiomas) diagnosed between 1966 and 1994 were
      retrieved from the Endocrine Pathology Registry of the Armed Forces Institute of
      Pathology. Histologic features (in 10 cases) as well as histochemical and
      immunohistochemical studies (in 6 cases) were reviewed. Long term patient follow
      up data were obtained in 9 cases. RESULTS: The patients included 8 females and 2
      males ages 2-61 years (mean age, 28.9 years) at initial presentation. The tumors
      were circumscribed and occurred predominantly (in 6 of 10 cases) in the tail of
      the pancreas. The multicystic, serous, or chylous fluid-filled cystic tumors
      ranged from 3 to 20 cm (average, 12.7 cm) in greatest dimension. Histologically,
      the tumors consisted of multilocular cystic spaces of various sizes, lined by
      endothelial cells. The stroma contained smooth muscle and mature lymphocytes.
      Immunohistochemistry determined the endothelial lining cells to be factor VIII-R
      antigen and CD31 positive (in all cases tested) but usually CD34 negative. All
      patients for whom follow-up data were obtained (n=9) were alive without evidence
      of disease an average of 7.2 years after initial diagnosis. CONCLUSIONS:
      Pancreatic lymphangiomas occur predominantly in females within a wide age range.
      Multilocular, fluid-filled cysts, with endothelial immunoreactivity for factor
      VIII-R antigen and CD31, are characteristic of these tumors. Complete surgical
      excision of these benign tumors resulted in excellent long term prognoses for all
      patients studied.

PMID- 9610695
TI  - The prognostic significance of the biomarkers p21WAF1/CIP1, p53, and bcl-2 in
      laryngeal squamous cell carcinoma.
AB  - BACKGROUND: The clinical course of laryngeal squamous cell carcinoma (LSCC)
      varies considerably among patients. New biologic markers are needed to facilitate
      the stratification of individual patients within the conventional
      clinicopathologic stages of LSCC. METHODS: Eighty-three LSCCs from an equal
      number of patients who received at least 10 years of follow-up were investigated
      for p53, p21WAF1/CIP1, and bcl-2 protein expression by immunohistochemical
      techniques. The results were correlated with various clinicopathologic
      parameters, DNA content, and patient outcome by univariate and multivariate
      statistical analyses. RESULTS: Stage IV disease, large tumor size (>3 cm),
      positive lymph node status, extranodal extension, and p53 overexpression (in >
      75% of cells) correlated significantly with prognosis in univariate analysis.
      There was no correlation between patient outcome and age, gender, race,
      histologic differentiation, or expression of bcl-2 or p21WAF1/CIP1. In
      multivariate analysis, lymph node status and p53 overexpression were the only
      factors significantly associated with survival. CONCLUSIONS: High p53 expression
      and positive lymph node status were independent predictors of the outcomes of
      patients with LSCC. These factors may assist in prognostication and better
      classification of patients for treatment.

PMID- 9610696
TI  - A phase I clinical and pharmacologic study of a carboplatin and irinotecan
      regimen combined with recombinant human granulocyte-colony stimulating factor in
      the treatment of patients with advanced nonsmall cell lung carcinoma.
AB  - BACKGROUND: This Phase I study was designed to determine the toxicity and
      efficacy of a carboplatin and irinotecan (CPT-11) regimen with recombinant human
      granulocyte colony-stimulating factor (rhG-CSF) support for patients with
      advanced nonsmall cell lung carcinoma. METHODS: Treatment consisted of
      carboplatin administered intravenously (i.v.) on Day 1 plus CPT-11 i.v. on Days
      1, 8, and 15. The carboplatin dose was calculated using Calvert's formula, where
      the target area under the plasma concentration versus the time curve (AUC) was 5
      or 6 mg x min/mL. rhG-CSF (2 microg/kg) was administered daily, except on Days 1,
      8, and 15, until the leukocyte count exceeded 20,000/mm3 (10,000/mm3 after Day
      16). Cycles were repeated every 4 weeks. Groups entered the trial at escalating
      CPT-11 and carboplatin dose levels of 60 mg/m2 and 5 mg x min/mL, 70/5 and 60/6.
      RESULTS: Twenty-one patients were enrolled in this study, of whom 20 were
      assessable for toxicity and therapeutic efficacy. Two of 6 patients experienced
      Grade 4 diarrhea at the 70/5 dose level, suggesting that this was the maximum
      tolerated dose (MTD). However, the 60/6 dose level was included because
      toxicities were very mild at the 60/5 dose level. At the 60/6 dose level, 1 of 6
      patients experienced severe, life-threatening toxicity. Therefore, subsequent
      dose escalation was stopped and the study terminated. There were 7 responses
      (35%) among the 20 patients. At the 60/6 dose level (n=5), the observed
      carboplatin AUC after aiming for a target AUC of 6 was 5.9+/-0.9 mg x min/mL, as
      expected, although the AUCs of both CPT-11 and its active metabolite, SN-38, were
      lower than expected. CONCLUSIONS: The recommended doses for Phase II studies are
      60 mg/m2 of CPT-11 and a target AUC of 5 mg x min/mL for carboplatin, plus rhG
      CSF. The combination of AUC-based carboplatin and CPT-11 with rhG-CSF support
      appears to be an active regimen in the treatment of patients with NSCLC.

PMID- 9610697
TI  - Granulocyte-macrophage-colony stimulating factor stimulates tumor invasiveness in
      squamous cell lung carcinoma.
AB  - BACKGROUND: Bronchial epithelial cells produce a significant amount of
      granulocyte-macrophage-colony stimulating factor (GM-CSF), which is believed to
      mediate both the host defense and inflammation. Recently, GM-CSF has been
      demonstrated to be produced by several tumor cells and also to be associated with
      tumor growth and metastasis. In the current study, the authors investigated the
      biologic role of GM-CSF produced by squamous cell lung carcinoma. METHODS: The
      production of GM-CSF from 17 human lung carcinoma cell lines was determined by an
      enzyme-linked immunoabsorbent assay. In vitro invasiveness was investigated by
      using a Biocoat Matrigel (Collaborative Biomedical Products, Bedford, MA)
      precoated invasion chamber. The activity of the matrix metalloproteinases (MMPs)
      were examined by gelatin zymography. The expression of GM-CSF in 113 cases of
      resected nonsmall cell lung carcinoma was analyzed immunohistochemically, and the
      association between the expression of GM-CSF and clinicopathologic features was
      investigated. RESULTS: The production of GM-CSF by squamous cell carcinoma cell
      lines was closely related to the in vitro invasiveness and MMP activity of the
      cancer cells. Recombinant GM-CSF stimulated the invasiveness of less invasive LK
      2 and LC-1 cells in a dose-dependent manner, and this stimulation was abrogated
      by the neutralizing anti-GM-CSF antibody. Furthermore, anti-GM-CSF antibody
      decreased the invasiveness of highly invasive EBC-1 and NCI-H157 cells. GM-CSF
      also increased the MMP activity of LK-2 and LC-1 cells. Of 113 resected nonsmall
      cell lung carcinomas, 30 of 71 squamous cell carcinomas (42.3%), and 24 of 42
      adenocarcinomas (57.1%) stained positively for GM-CSF. The expression of GM-CSF
      in squamous cell carcinomas was associated with the local invasion by the primary
      tumor. CONCLUSIONS: These results suggest that the production of GM-CSF is
      involved in both the in vitro invasiveness and the local progression of squamous
      cell carcinoma of the lung.

PMID- 9610698
TI  - Radioimmunodetection of human myeloma xenografts with a monoclonal antibody
      directed against a plasma cell specific antigen, HM1.24.
AB  - BACKGROUND: To develop a new immunologic approach to multiple myeloma, the
      authors generated a monoclonal antibody against a human plasma cell specific
      antigen, HM1.24. Their previous study showed the antitumor effect of this
      antibody in severe combined immunodeficiency (SCID) mice bearing human myeloma
      xenografts. In the current study, the efficacy of anti-HM1.24 immunoglobulin (Ig)
      G and its F(ab')2 fragment were evaluated for radioimmunologic detection of the
      myeloma xenografts. METHODS: SCID mice bearing subcutaneous RPMI 8226 tumors were
      injected with 125I-labeled antibodies, and radioactivity in the tumor and normal
      tissues was measured. Radioimmunoscintigraphy and autoradiography were performed
      to investigate the distribution of the antibodies. RESULTS: In comparative
      biodistribution studies, the maximum tumor localization index of anti-HMl.24
      F(ab')2 fragment was significantly higher than that of anti-HM1.24 IgG. Anti
      HM1.24 F(ab')2 consistently had higher tumor-to-tissue ratio than anti-HM1.24 IgG
      and gave distinct tumor images by radioimmunoscintigraphy. Autoradiographic study
      showed that anti-HM1.24 F(ab')2 penetrated the tumor mass more uniformly than
      whole IgG antibody. CONCLUSIONS: These results indicate that anti-HM1.24 antibody
      has the potential to provide a new approach to the immunodetection and
      immunotherapy of multiple myeloma and related plasma cell dyscrasias.

PMID- 9610699
TI  - Subdiaphragmatic and intrathoracic paraspinal malignant peripheral nerve sheath
      tumors: a clinicopathologic study of 25 patients and 26 tumors.
AB  - BACKGROUND: To determine the effects of anatomic site on the presentation and
      diagnosis of malignant peripheral nerve sheath tumors (MPNSTs) and on the
      treatment and outcomes of the patients, the authors initiated a study of these
      tumors at different sites. An earlier report described MPNSTs of the buttock and
      lower extremity, and the current series analyzes those presenting at
      intrathoracic (IT) and subdiaphragmatic (SD) paraspinal sites. METHODS: The
      authors reviewed data on patients with paraspinal MPNSTs who were seen at
      Memorial Hospital during the period 1960-1995 and for whom histologic slides were
      available. Various clinicopathologic parameters and their effects on patient
      outcomes were examined. RESULTS: Twenty-five patients with 26 tumors were
      evaluated. Seven tumors were IT and 19 were SD; 60% of the patients had
      neurofibromatosis type 1 (NF1). Most patients presented with pain, and a
      diagnostic delay (of 3 months to 2 years) was often noted. Mean tumor sizes for
      SD and IT tumors were 14.3 cm and 6.6 cm, respectively. Most MPNSTs were composed
      of spindle cells in fascicles. Twenty-seven percent exhibited divergent
      differentiation. Twenty-four tumors were high grade, and a low grade component
      was identified in 8 tumors. Surgical resection was attempted for 23 tumors (88%),
      but complete resection was achieved in only 6 cases (23%). Eighty percent of the
      patients died of their tumors, 2-year and 5-year survival rates were 35% and 16%,
      and median survival was 8.5 months. Significant prognostic factors were tumor
      size <5 cm, the presence of a low grade component, and complete tumor resection.
      CONCLUSIONS: Paraspinal MPNSTs have more aggressive behavior than peripherally
      located tumors, mainly because of the difficulty encountered in resecting them
      completely. Prognoses of patients with MPNST at this site appear to be affected
      by resection status, tumor size, and tumor grade.

PMID- 9610700
TI  - A randomized trial of long term adjuvant tamoxifen plus postoperative radiation
      therapy versus radiation therapy alone for patients with early stage breast
      carcinoma treated with breast-conserving surgery. Stockholm Breast Cancer Study
      Group.
AB  - BACKGROUND: The use of adjuvant tamoxifen to treat postmenopausal breast
      carcinoma patients as an adjunct to primary surgery is well established. The
      current study reports the long term results for a low risk stratum in a
      randomized trial of adjuvant tamoxifen. The main focus of this analysis was to
      determine whether tamoxifen would result in a reduced local failure rate for
      lymph node negative, postmenopausal patients treated with breast-conserving
      surgery and postoperative radiotherapy. METHODS: The study population included
      432 lymph node negative, postmenopausal patients with invasive breast carcinoma
      (classified as T1-T2) who underwent breast-conserving surgery followed by
      radiotherapy in Stockholm during the period 1976-1990. The patients constituted a
      separate stratum of the Stockholm Adjuvant Tamoxifen Trial, which included a
      total of 2729 patients. Of 432 patients, 213 received 40 mg of tamoxifen daily
      for either 2 or 5 years. The median follow-up time was 8 years (range, 5-19
      years). RESULTS: At 10 years, the overall survival was 90% for the tamoxifen
      group and 88% for the control group. The event free survival at 10 years was 80%
      for the tamoxifen group and 70% for the control group (P=0.03). Tamoxifen reduced
      the overall rate of ipsilateral (hazard ratio=0.4, 95% confidence interval
      [CI]=0.2-0.9, P=0.02) and contralateral breast tumor recurrences (hazard
      ratio=0.4, 95% CI=0.1-1.1, P=0.06). Trends toward a reduced number of distant
      metastases (hazard ratio=0.6, 95% CI=0.3-1.2, P=0.1) and deaths due to breast
      carcinoma (hazard ratio=0.5, 95% CI=0.2-1.2, P=0.1) also were observed.
      CONCLUSIONS. The addition of tamoxifen to radiotherapy for postmenopausal, lymph
      node negative breast carcinoma patients treated with breast-conserving surgery
      resulted in a reduced rate of ipsilateral and contralateral breast tumor
      recurrences. The avoidance of salvage mastectomies, reexcisions, and new
      contralateral malignancies justifies the use of tamoxifen even in the treatment
      of patients with a 10-year survival rate of 90%.

PMID- 9610701
TI  - The number of positive margins influences the outcome of women treated with
      breast preservation for early stage breast carcinoma.
AB  - BACKGROUND: There are conflicting reports regarding whether focally positive
      surgical margins influence tumor control in breast-conservation therapy. The
      authors have evaluated the relation between positive surgical margins on tumor
      control and whether the number of positive margins affects tumor control in
      patients undergoing reexcision lumpectomy. METHODS: From 1978 to 1994, 453
      American Joint Committee on Cancer Stage I/II breast carcinoma patients were
      treated at Thomas Jefferson University Hospital with breast conservation therapy.
      Patients underwent excisional biopsy and margin sampling with shaved biopsies of
      the tumor cavity. The entire breast received 45 grays (Gy) with a 20-Gy iridium
      192 implant or an electron boost. Eighty-six patients had microscopically
      positive margins (19%), and the remainder had confirmed negative margins. The
      median follow-up time was 45 months. RESULTS: Local tumor control rates for
      patients with negative margins at 5 and 10 years were 94% and 87%, respectively,
      compared with 86% and 69%, respectively, for those patients with positive margins
      (P=0.005). The disease free survival rates for the negative margin group at 5 and
      10 years were 91% and 82%, respectively, compared with 76% and 71%, respectively,
      for the positive margin group (P=0.001). Overall survival rates for patients with
      negative margins at 5 and 10 years were 95% and 84%, respectively, compared with
      87% and 78%, respectively, for those with positive margins (P=0.047). When
      comparing the negative margin group with the one positive margin group, there was
      no significant difference in local tumor control (P=0.12). However, women with
      two or more positive margins had an inferior local tumor control compared with
      those women with negative margins (P=0.002). CONCLUSIONS: Patients with positive
      margins have a higher risk for local failure and worse survival when undergoing
      breast conservation therapy. Inferior local tumor control was noted in those
      patients with two or more positive margins.

PMID- 9610702
TI  - The benefits of mammography are not limited to women of ages older than 50 years.
AB  - BACKGROUND: Although the benefits of mammography are established in women age <
      or = 50 years, its use in women age < 50 years is controversial. It is the
      purpose of this study to determine whether the better outcome in mammographically
      detected breast carcinoma compared with clinically detected breast carcinoma
      observed in women age > or = 50 years also is observed in women age < 50 years.
      METHODS: The authors analyzed 869 cases of Stage I and II breast carcinoma in
      women treated with breast-conserving therapy between 1984-1994. The median follow
      up was 43 months (range, 3-128 months). Three hundred and eighteen patients (37%)
      presented with mammographic abnormalities without clinical signs of disease and
      551 patients (63%) presented with clinical signs of disease. The median age of
      the patients was 56 years (range, 22-88 years). Three hundred and four patients
      (35%) were age < 50 years. RESULTS: Mammographically detected tumors in women age
      < 50 years were of similar size to those in women age > or = 50 years (median 1.1
      cm vs. 1.0 cm). Axillary lymph node involvement and tumor grade were not
      significantly different between these two groups. However, in women age < 50
      years the clinically detected tumors were found to be significantly larger, more
      likely to be axillary lymph node positive, and of higher grade compared with
      tumors in older women. Consequently, in patients with mammographically detected
      tumors, there was no significant difference in recurrence free survival (RFS)
      between women age < 50 years compared with women age > or = 50 years (90% and
      92%, respectively; P=0.4), whereas in patients with clinically detected tumors
      there was a significant difference in 5-year RFS (77% vs. 87%, respectively;
      P=0.02). CONCLUSIONS: Mammography results in the diagnosis of smaller and lower
      grade breast carcinoma. If mammographically detected, there appears to be no
      difference in RFS between women age < 50 years and those women age > or = 50 but
      there is a difference if the tumors are clinically detected. If left to grow to
      the size necessary for clinical detectability, the disease appears to be more
      aggressive in younger women.

PMID- 9610703
TI  - Predicting the prognoses of breast carcinoma patients with positron emission
      tomography using 2-deoxy-2-fluoro[18F]-D-glucose.
AB  - BACKGROUND: Positron emission tomography (PET) with 2-deoxy-2-fluoro[18F]-D
      glucose (FDG) can provide quantitative information about tumor glucose
      metabolism. The prognostic value of this technique was evaluated for breast
      carcinoma patients. METHODS: FDG PET was performed on 70 patients with primary
      breast carcinoma, and the differential absorption ratio (DAR) was calculated as
      an index of FDG uptake. Overall and relapse free survival curves were created by
      the Kaplan-Meier method, and differences between the curves were analyzed with
      the log rank test. For multivariate analysis, the Cox proportional hazards
      regression model was used. RESULTS: The mean DAR was 2.61+/-1.61 standard
      deviation (range, 0.65-9.39). According to the grade of DAR, patients were then
      classified into high DAR (> or =3.0) and low DAR (<3.0) groups. The high DAR
      group had significantly worse prognoses for both overall and relapse free
      survival (P < 0.0005 and P < 0.0001, respectively). In multivariate analysis, DAR
      was an independent predictor of the relapse free survival of breast carcinoma
      patients (P=0.0377). CONCLUSIONS: DAR, as determined by FDG PET, may be useful as
      a prognostic indicator for patients with primary breast carcinoma.

PMID- 9610704
TI  - Screening mammography beginning at age 40 years: a reappraisal of cost
      effectiveness.
AB  - BACKGROUND: Several recent studies have added significant information regarding
      the benefit of screening mammography, especially in the 40-49-years age group.
      This new information makes it important to reassess the cost-effectiveness of
      screening. METHODS: A Markov model was used to study the cost-effectiveness of 4
      age-related screening strategies: 1) annually from ages 40-79 years; 2) annually
      from ages 40-64 years and biennially from ages 65-79 years; 3) annually from ages
      40-49 years and biennially from ages 50-79 years; and 4) annually from ages 40-79
      years in high risk women (10%) and biennially from ages 40-49 years followed by
      annually from ages 50 -79 years in normal risk women (90%). An additional
      strategy simulating hormone status and estrogen exposure was evaluated. Cost
      effectiveness was expressed as marginal cost per year-life saved (MCYLS).
      RESULTS: The MCYLS varied from $18,800 to $16,100. For all strategies this was
      within the range of other generally acceptable diagnostic and therapeutic medical
      procedures. There was a 14% decrease in MCYLS from the least cost-effective to
      the most cost-effective strategy. CONCLUSIONS: Cost-effectiveness of four age
      related mammographic screening strategies was evaluated. The MCYLS for all
      strategies was within a generally accepted range. With increasing concerns
      regarding the cost of health care, this information may be useful in health
      policy decision-making.

PMID- 9610705
TI  - Pretreatment surgical staging of patients with cervical carcinoma: the case for
      lymph node debulking.
AB  - BACKGROUND: The routine use of extraperitoneal surgical staging prior to
      radiation therapy in patients with bulky or locally advanced cervical carcinoma
      remains controversial. METHODS: A review was performed of 266 patients with
      cervical carcinoma who underwent extraperitoneal pelvic and paraaortic
      lymphadenectomy prior to receiving radiotherapy. Patients were divided into
      groups based on their lymph node status. Group A had negative lymph nodes; Group
      B had resected, microscopic lymph node metastases; Group C had macroscopically
      positive lymph nodes that were resectable at the time of surgery; and Group D had
      unresectable lymph nodes. All patients received standard radiotherapy utilizing
      external beam and brachy-therapy. Patients with lymph node metastases received
      extended field irradiation. Survival probabilities were computed by the Kaplan
      Meier product limits method with statistical significance determined by the
      Mantel-Cox log rank test. RESULTS: Lymph node metastases were detected in 50% of
      patients. Five- and 10-year disease free survival rates were similar for all
      patients in Groups B and C. All patients in Group D recurred. There was a 10.5%
      incidence of severe radiation-related morbidity and a 1.1% incidence of treatment
      related deaths. CONCLUSIONS: Pretreatment extraperitoneal staging of patients
      with bulky or locally advanced cervical carcinoma may afford a survival benefit
      via the debulking of macroscopically positive lymph nodes without significantly
      increasing treatment-related morbidity or mortality.

PMID- 9610706
TI  - Diagnosis of squamous cell carcinoma arising from mature cystic teratoma of the
      ovary.
AB  - BACKGROUND: The prognoses of patients with squamous cell carcinoma of the ovary
      are quite poor. However, preoperative diagnosis is difficult due to the rarity of
      this tumor and its similarity to mature cystic teratoma (MCT). The objective of
      this study was to assess the value of tumor markers and clinical characteristics
      in making a differential diagnosis between MCT and squamous cell carcinoma
      arising from MCT. METHODS: Between September 1979 and June 1996, 37 patients with
      ovarian squamous cell carcinoma arising from MCT were treated by the Tokai
      Ovarian Tumor Study Group. The authors evaluated tumor markers, tumor size, and
      age as parameters for differentiation between MCT and squamous cell carcinoma
      arising from MCT. Diagnostic efficiency was calculated as the sensitivity
      multiplied by the specificity. RESULTS: There were significant differences (P <
      or = 0.0002) in age, tumor size, and levels of squamous cell carcinoma antigen
      (SCC), CA125, and CEA, as well as a significant difference (P < or = 0.0396) in
      the CA19-9 level between MCT and squamous cell carcinoma arising from MCT.
      Diagnostic efficiency was highest for SCC (63.0%), followed by CA125 (50.7%).
      Receiver operating characteristic (ROC) curves demonstrated that CEA was the best
      screening marker for squamous cell carcinoma arising from MCT, whereas age and
      tumor size were better markers than CA125 or CA19-9. The optimal cutoff values
      for age and tumor size were 45 years and 99 mm, respectively, according to ROC
      analysis. CONCLUSIONS: These findings demonstrate that age and tumor size are
      important factors in making a differential diagnosis. In addition, SCC and CEA
      levels should be measured in patients age 45 years or older who have an MCT-like
      ovarian tumor larger than 99 mm in greatest dimension.

PMID- 9610707
TI  - Prostate specific membrane antigen expression in prostatic intraepithelial
      neoplasia and adenocarcinoma: a study of 184 cases.
AB  - BACKGROUND: Prostate specific membrane antigen (PSM) is a membrane-bound antigen
      that is highly specific for benign and malignant prostate epithelial cells. Its
      expression in high grade prostatic intraepithelial neoplasia (PIN) has not been
      compared with that in prostate carcinoma. METHODS: The authors performed an
      immunohistochemical study of representative sections from 184 radical
      prostatectomies from previously untreated patients with pathologic stage T2N0M0
      adenocarcinoma treated at the Mayo Clinic between 1987 and 1991. Affinity
      purified monoclonal antibody 7E11-5.3 directed against PSM was employed at a
      concentration of 20 microg/mL overnight. For comparison, serial sections in each
      case were stained with prostate specific antigen (PSA). Staining for all
      antibodies was performed using the streptavidin-biotin method. For each case, the
      percentage of immunoreactive cells in benign epithelium, PIN, and adenocarcinoma
      was estimated in increments of 10%. Cox proportional hazards models were used to
      identify the risk of carcinoma recurrence according to the number of
      immunoreactive PIN or cancer cells for PSM and PSA; the date of radical
      prostatectomy was used as the starting time, and serum PSA (biochemical) failure
      or clinical failure was the event. PSA biochemical failure was defined as serum
      PSA > 0.2 ng/mL at least 30 days after surgery. RESULTS: Intense cytoplasmic
      immunoreactivity for PSM was observed in the benign and neoplastic epithelial
      cells in all cases (100% of cases staining). The number of cells staining was
      lower in benign epithelium and PIN than in adenocarcinoma (69.5+/-17.3% [range,
      20-90%] vs. 77.9+/-13.2% [range, 30-100%] vs. 80.2+/-13.7% [range, 30-100%],
      respectively). With rare exceptions, basal cells were negative, and there was no
      immunoreactivity of the prostate stroma, urothelium, or vasculature.
      Adenocarcinoma gave the most intense and extensive staining, and the highest
      grades of adenocarcinoma (Gleason primary patterns 4 and 5) showed staining in
      virtually every cell; there was greater heterogeneity of staining in lower grades
      of adenocarcinoma. By contrast, PSA immunoreactivity was more intense and
      extensive in benign epithelium than in PIN and adenocarcinoma. The number of
      immunoreactive PIN or cancer cells for PSM and PSA was not predictive of PSA
      biochemical or clinical failure as defined in this study. CONCLUSIONS: PSM was
      expressed in all cases of prostate adenocarcinoma, with the greatest extent and
      intensity observed in the highest grades. The expression increased incrementally
      from benign epithelium to high grade PIN or adenocarcinoma. Conversely, PSA
      showed the greatest staining in benign epithelium, with decreased expression
      incrementally from benign epithelium to high grade PIN or adenocarcinoma.
      Expression of PSM is clinically useful for the identification of prostate
      epithelium, particularly PIN or adenocarcinoma, and its expression is regulated
      independent of PSA. The number of PSM immunoreactive cells was not predictive of
      recurrence, most likely because of the presence of abundant immunoreactivity in
      most cases, or because of differential expression in primary and metastatic
      disease.

PMID- 9610708
TI  - The prognostic significance of MIB-1, p53, and DNA flow cytometry in completely
      resected primary meningiomas.
AB  - BACKGROUND: Despite the availability of clinical and pathologic parameters of
      prognosis, the behavior of an individual meningioma may be difficult to predict.
      In a recent review of gross totally resected (GTR) meningiomas, the authors found
      strong associations between microscopic brain invasion, increased mitotic rate (>
      or = 4/10 high-power fields), the presence of at least 3 of 4 morphologic
      variables (sheeting, hypercellularity, macronucleoli, and small cells), and
      decreased recurrence free survival (RFS). In this study, they assessed the
      prognostic value of three ancillary techniques: DNA flow cytometry, MIB-1
      labeling, and p53 protein expression. METHODS: The authors evaluated primary GTR
      meningiomas from 425 patients with DNA flow cytometry, immunostaining for MIB-1,
      and determination of p53 protein expression. The patients were followed until
      death or for a median of 8.9 years. RESULTS: An MIB-1 labeling index (LI) of > or
      = 4.2%, identified in 8% of cases, was strongly associated with decreased RFS in
      univariate analysis (P=0.0001). Fourteen percent contained aneuploid cell
      populations, and 48% exhibited a p53 LI of >10%. Neither variable was associated
      with decreased RFS. Further analysis revealed a close association between MIB-1
      LI and mitotic index, the latter being the parameter of greatest significance in
      multivariate analysis. CONCLUSIONS: MIB-1 LI is a useful adjunct to routine
      histologic evaluation of meningiomas and appears to be of greatest value in the
      evaluation of tumors exhibiting borderline atypia. In contrast, our data suggest
      that, regarding patients with primary GTR meningiomas, neither flow cytometry nor
      p53 immunohistochemistry provides useful prognostic information.

PMID- 9610709
TI  - Final report of a phase II evaluation of paclitaxel in patients with advanced
      squamous cell carcinoma of the head and neck: an Eastern Cooperative Oncology
      Group trial (PA390).
AB  - BACKGROUND: A number of single agents have been tested in patients with carcinoma
      of the head and neck receiving palliative treatment. In general, 15-30% of
      patients achieve a partial response lasting 3-4 months. Treatment has not been
      shown to alter survival rates. It is clear that new drugs with potentially
      greater activity need to be identified. For this purpose, the Eastern Cooperative
      Oncology Group conducted a Phase II evaluation of paclitaxel. METHODS: Patients
      with recurrent, metastatic, or locally advanced, incurable squamous cell
      carcinoma of the head and neck were eligible. The dose and schedule tested was
      the maximum tolerable dose of 250 mg/m2 determined from Phase I trials using a 24
      hour infusion schedule and granulocyte-colony stimulating factor support. Courses
      were given at 3-week intervals until progression of disease was documented. Dose
      modifications were specified for hematologic toxicity and for neurotoxicity.
      RESULTS: Thirty-four patients were registered on study and 30 were eligible.
      Severe or life-threatening granulocytopenia was the most frequent toxicity
      observed, occurring in 91% of patients. Prior to response evaluation, one patient
      died of sepsis and one died of a myocardial infarct. Response was observed in 40%
      of eligible patients (4 complete and 8 partial responses). The median duration of
      response was 4.5 months (range, 2-20 months), with a median survival of 9.2
      months and a 1-year survival rate of 33%. CONCLUSIONS: These results indicate
      that paclitaxel is an active agent for the treatment of squamous cell carcinoma
      of the head and neck. Studies evaluating alternative infusion schedules and
      combination regimens currently are underway.

PMID- 9610710
TI  - The impact of mucositis on alpha-hemolytic streptococcal infection in patients
      undergoing autologous bone marrow transplantation for hematologic malignancies.
AB  - BACKGROUND: Antibacterial prophylaxis with quinolone antibiotics has resulted in
      an increase in streptococcal infections among bone marrow transplantation (BMT)
      recipients with myelosuppression. Oral ulceration (mucositis), which frequently
      occurs as a consequence of chemotherapy, has been implicated as a significant
      portal of entry for streptococci. The objectives of this study were to confirm
      the correlation between mucositis and streptococcal bacteremia, determine the
      risk associated with this correlation, and evaluate the impact of mucositis and
      streptococcal bacteremia on hospital course and costs associated with autologous
      BMT. METHODS: This was a retrospective, case-control study in which the charts of
      autologous BMT recipients treated for hematologic malignancies between 1990 and
      1996 were reviewed. Twenty-four patients were identified who met the criteria of
      autologous BMT; their blood cultures confirmed (x2) alpha-hemolytic streptococcal
      sepsis. A control group of 45 without positive cultures was matched by gender,
      age, diagnosis, and treatment to the study group. RESULTS: The results confirm
      that ulcerative mucositis is a significant risk factor for alpha-hemolytic
      streptococcal bacteremia among autologous BMT patients. Of the 24 patients with
      bacteremia, 15 of 24 (62%) had ulcerative mucositis, compared with 16 of 45 (36%)
      of patients in the control population (P < 0.05). Patients with ulcerative
      mucositis were found to be three times as likely to develop alpha-hemolytic
      streptococcal bacteremia as those without ulcerative mucositis (odds ratio=3.02).
      Both independently and as a cofactor associated with bacteremia, mucositis
      adversely affected the length of hospital stay (LOS). Of all the patients
      studied, those with oral ulcerations had a LOS of 34 days, compared with 29 days
      for patients without oral ulcerations (P < 0.05). Of patients in the study group,
      those with oral ulcerations stayed in the hospital 6 days longer than patients
      without oral ulcerations (40 days vs. 34 days, P < 0.05). CONCLUSIONS: Oral
      ulcerative mucositis is a significant, common, and important risk factor for
      alpha-hemolytic streptococcal bacteremia in BMT recipients with myelosuppression;
      it results in longer hospital stay and increased costs.

PMID- 9610711
TI  - A randomized comparison of the efficacy and toxicity of epirubicin and
      doxorubicin in the treatment of patients with non-Hodgkin's lymphoma.
AB  - BACKGROUND: Combination chemotherapy consisting of methotrexate, doxorubicin,
      cyclophosphamide, vincristine, prednisolone, and bleomycin (MACOP-B) has been
      frequently used for the treatment of non-Hodgkin's lymphoma. This randomized
      study was undertaken to assess the efficacy and toxicity of this regimen when
      either doxorubicin or epirubicin was used as the anthracycline drug. METHODS:
      Between April 1989 and December 1993, 211 previously untreated patients with
      intermediate grade and high grade non-Hodgkin's lymphoma were randomized to
      receive either doxorubicin (n=106) or epirubicin (n=105) with the MACOP-B
      regimen. These patients were followed through December 1996. Numerous clinical
      features predictive of response and survival were analyzed. Cardiac and
      noncardiac toxicity in the two treatment arms were compared. RESULTS: The median
      age of the patients was 48 years. Complete remission was experienced by 122
      patients (58.3%); 62 patients (58.5%) achieved complete remission in the
      doxorubicin arm and 60 (58.1%) in the epirubicin arm. Response rates, time to
      treatment failure, relapse data, and overall survival were comparable between the
      two arms. Morbidity due to mucositis, vomiting, peripheral neuropathy, and
      cardiotoxicity were also comparable. The overall mortality was 10%. Mortality due
      to neutropenic sepsis was considerably higher among patients who received
      epirubicin (10 patients) than among those who received doxorubicin (5 patients).
      Cardiac evaluation revealed no difference in toxicity between the two arms.
      CONCLUSIONS: Epirubicin was as effective as doxorubicin in terms of patients'
      responses to therapy. There was no difference in cardiotoxicity between the two
      treatment arms. However, in this study, the mortality due to neutropenic sepsis
      was significantly higher among patients treated with epirubicin.

PMID- 9610712
TI  - Lumpectomy margins and much more.

PMID- 9610713
TI  - Consensus conference on the classification of ductal carcinoma in situ.

PMID- 9610714
TI  - Pilot study--cimetidine enhances lymphocyte infiltration of human colorectal
      carcinoma: results of a small randomized control trial.

PMID- 9610715
TI  - Different risk factor patterns for high-grade and low-grade intraepithelial
      lesions on the cervix among HPV-positive and HPV-negative young women.
AB  - Risk factors for cervical intraepithelial neoplasia have most often been studied
      in high-grade lesions. Furthermore, in a high proportion of the studies, human
      papillomavirus (HPV), the most significant risk determinant of cervical
      neoplasia, was not taken into account when evaluating other risk factors. To
      compare risk factors for ASCUS (atypical cells of undetermined significance),
      LSIL (low-grade squamous intraepithelial lesion) and HSIL (high-grade squamous
      intraepithelial lesion), we conducted a case-control study among 20 to 29 year
      old women participating in a prospective cohort study in Copenhagen. It included
      131 women with ASCUS, 120 women with LSIL, 79 women with HSIL and 1,000 randomly
      chosen, cytologically normal, control women. All participants had a personal
      interview and a gynecological examination including a Pap smear and cervical
      swabs for HPV DNA detection using general primer-mediated polymerase chain
      reaction. The most significant risk determinant of all 3 disease categories was
      the presence of genital HPV DNA. The risk factor pattern was nearly identical for
      ASCUS and LSIL, but differed significantly from that for HSIL. Stratified
      analysis by HPV-status showed that, apart from, respectively, smoking and parity
      among HPV-positive women, and smoking and number of sex partners among HPV
      negative women, no additional risk factors were observed for ASCUS and LSIL. In
      contrast, among HPV-negative women with HSIL, long-term use of oral
      contraceptives was the most important risk factor. However, our result should be
      taken with great caution as it is based on very small numbers, and as it is
      unknown whether the HPV-negative lesions constitute a true entity. Among HPV
      positive women, the risk of HSIL was associated with e.g., years of sex life
      without barrier contraceptive use, early age at first genital warts and smoking.
      Whether the risk factors that are applicable only to HSIL represent factors
      related to progression remains unknown.

PMID- 9610716
TI  - Expression of somatostatin receptor subtypes in human brain tumors.
AB  - Expression of mRNA for the 5 somatostatin receptors (sst1-5) was characterized by
      Northern blot and RT-PCR analysis in 20 meningioma and 9 glioma samples. sst1
      mRNA was detectable by Northern blots of poly-A+ RNA in meningiomas but not
      gliomas. In contrast, sst2 mRNA was readily detected by Northern blots of total
      RNA as a major 2.3 kb transcript and 2 minor 4.3 kb and 8 kb transcripts in all
      meningiomas and 6 out of 9 gliomas. Quantitation of the 2.3 kb sst2 mRNA showed
      that 15 out of 20 tumors expressed 1.3- to 33-fold higher levels than control
      normal human brain. Mean sst2 mRNA for the 20 meningioma samples was 978% that of
      normal brain. Three gliomas showed 7- to 14-fold higher sst2 mRNA than normal
      brain whereas the remaining samples displayed very low or undetectable levels.
      Immunocytochemistry of meningioma and glioma samples, with a sst2-specific
      antibody revealed immunoreactivity in tumor cells and peritumoral tissue, with
      prominent expression in blood vessels. mRNA for sst3,4,5 could not be detected by
      Northern blots in any of the tumors. RT-PCR analysis of meningiomas and gliomas
      revealed the following percent of tumors positive for a given sst mRNA: sst1
      (86%), sst2 (100%), sst3 (60%), sst4 (58%), and sst5 (67%); 85% of tumors
      expressed 3 of the 5 subtypes. No correlation was found between the pattern of
      expression of sst mRNA and tumor type, location, and histology for either the
      meningiomas or gliomas. Our results show that meningiomas and gliomas are all
      positive for at least one sst subtype, the majority expressing multiple subtypes.
      sst2 is the most abundant isoform with a rich expression in both tumor and
      peritumoral tissue especially blood vessels.

PMID- 9610717
TI  - Demographic characteristics, pigmentary and cutaneous risk factors for squamous
      cell carcinoma of the skin: a case-control study.
AB  - We conducted a case-control study of squamous cell carcinoma of the skin (SCC) in
      a cohort of people followed from 1987 to 1994. Subjects were residents of
      Geraldton, Western Australia, who were between 40 and 64 years of age in 1987. On
      2 occasions, in 1987 and 1992, dermatologists examined participants for skin
      cancers. Subjects were also asked on several occasions about skin cancers that
      they had had treated. Migrants to Australia had reduced risks of SCC.
      Furthermore, people who migrated to Australia early in life or, equivalently,
      lived in Australia for a long time had a higher risk than immigrants who arrived
      later in life or more recently. People who had southern European ancestry had a
      much lower risk of SCC than other subjects, most of whom were of British or
      northern European origin. Among Australian-born subjects of British or northern
      European ancestry, the skin's sensitivity to sunlight was strongly associated
      with SCC. The pigmentary traits of hair colour, eye colour and skin colour showed
      weaker associations. The degree of freckling on the arm was strongly predictive
      of risk. The risk of SCC increased strongly with increasing evidence of cutaneous
      solar damage and was most strongly associated with the number of solar keratoses.
      Our results show that sensitivity to sunlight and high levels of exposure to
      sunlight are important determinants of the risk of SCC.

PMID- 9610718
TI  - No evidence of replication error phenotype in primary gastric lymphoma of mucosa
      associated lymphoid tissue.
AB  - Replication error (RER) phenotype, caused by deficiency of DNA mismatch repair
      genes and revealed by widespread microsatellite instability, has been detected in
      subsets of a wide variety of solid tumors, but rarely in lymphomas in general. So
      far, the involvement of RER phenotype in the pathogenesis of gastric lymphoma of
      mucosa-associated lymphoid tissue (MALT) type has not been conclusively
      established. We therefore examined 9 microsatellite loci on 5 chromosomes
      [D2S123, D3S11, D3S1261, D3S1262, D3S1265, D6S262, D18S559, a CTTT(T) repeat in
      intron 20 of RBI gene and a CA repeat in p53 locus] in 33 cases of primary
      gastric MALT lymphoma for evidence of microsatellite instability by polymerase
      chain reaction using primers end-labeled with [gamma-33P] ATP. Although novel
      length allele was observed in 7 of 33 cases (21.2%), none of these 7 cases showed
      changes in more than one locus. RER phenotype was scored as positive in a case
      when more than 1 of the 9 examined microsatellite loci showed length alterations.
      Accordingly, none of the 33 cases had a RER phenotype. This result suggests that
      the pathogenesis of gastric MALT lymphoma does not involve RER phenotype. It is
      consistent with the general observations in lymphomas, but is highly in contrast
      to a previous report showing more than 50% of MALT lymphomas with the RER
      phenotype.

PMID- 9610719
TI  - Selective down-regulation of human papillomavirus transcription by 2
      deoxyglucose.
AB  - The glycolytic pathway inhibitor 2-deoxyglucose (2-DG) is capable of suppressing
      the transcription of the human pathogenic papillomavirus type 18 (HPV 18) in
      cervical carcinoma cells and derived non-tumorigenic somatic cell hybrids at the
      level of transcription initiation. HPV down-regulation is selective, since other
      reference genes are not affected or even up-regulated under the same experimental
      conditions. Moreover, 2-DG appears to restore the normal half-life of the tumor
      suppressor gene product p53, because the protein is strongly up-regulated after
      HPV 18 E6/E7 suppression. The observed 2-DG-effect is not cytotoxic and is
      reversible after refeeding with fresh medium. HPV 18 suppression by 2-DG can be
      completely abrogated by simultaneous treatment with the intracellular Ca2+
      antagonist TMB-8, indicating that Ca2+, a known intracellular "second messenger",
      is involved in this process. Elevated c-myc and p53 expression appears to be
      responsible for the time-dependent accumulation of apoptotic cells after
      prolonged 2-DG treatment. The finding that 2-DG acts selectively against the
      expression of a human pathogenic papillomavirus strongly suggests that an
      appropriate level of glycolysis is not only a peculiarity of growing tumors, but
      even may be an essential prerequisite for the maintenance of virus-specific E6/E7
      gene expression. Our results may have substantial implications for the potential
      therapeutic application of 2-DG or other glucose derivatives in the treatment of
      precancerous and malignant HPV-associated lesions.

PMID- 9610720
TI  - Breast-cancer incidence in relation to height, weight and body-fat distribution
      in the Dutch "DOM" cohort.
AB  - In a cohort of 11,663 participants in a breast-cancer screening program, height,
      weight, waist circumference and hip circumference were measured, and information
      about menstrual and reproductive history was obtained by questionnaire. After
      exclusion of 83 women with unclear menopausal status, the subjects were divided
      into 3 sub-cohorts: 5,891 women who were pre-menopausal at the time of data
      collection, 3,521 women who had entered the study after natural menopause, and
      2068 women who had been hysterectomized and/or ovariectomized. After a median
      follow-up of 10.6 years, 147, 76 and 52 incident cases of breast cancer were
      detected in the 3 respective sub-cohorts. No statistically significant
      association was found in any of the sub-cohorts between breast-cancer risk and
      height, weight, body-mass index (BMI) or hip circumference. In the sub-cohort of
      women with natural menopause, however, risk of breast cancer was positively and
      significantly associated with the ratio of waist-to-hip circumferences (WHR) (RR
      = 2.63 for upper vs. lower quartile), and this association did not change after
      adjustment for variations in disease risk related to body height and weight.
      Although similar to observations in other cohort studies showing positive
      associations between obesity and breast-cancer risk in post-menopausal women, our
      results are different, in that WHR and not BMI appears to be the more specific
      indicator of breast-cancer risk.

PMID- 9610721
TI  - Characterization of human colon cancer antigens recognized by autologous
      antibodies.
AB  - The screening of cDNA expression libraries derived from human tumors with
      autologous antibody (SEREX) has proven to be a powerful method for defining the
      structure of tumor antigens recognized by the humoral immune system. In the
      present study, 48 distinct antigens (NY-CO-1-NY-CO-48) reactive with autologous
      IgG were identified by SEREX analysis in 4 patients with colon cancer. Sequencing
      analysis showed that 17 of the cDNA clones were previously uncharacterized
      molecules and 31 represented known gene products. The individual cDNA clones were
      analyzed in the following manner: a search for mutations or other structural
      changes; an analysis of mRNA expression in a panel of normal tissues; and a
      frequency analysis of the antibody response to the expressed product in the sera
      of colon cancer patients and normal individuals. The initial analysis showed NY
      CO-13 to be a mutated version of the p53 tumor suppressor gene. Three of the 48
      antigens showed a differential pattern of mRNA expression, with NY-CO-27
      (galectin-4) expressed primarily in gastrointestinal tract, and NY-CO-37 and -38
      showing a pattern of tissue-specific isoforms. With regard to immunogenicity, 20
      of the 48 antigens were detected by allogeneic sera; 14 of these were reactive
      with sera from both normal donors and cancer patients, and 6 other clones (NY-CO
      8, -9, -13, -16, -20 and -38) reacted exclusively with sera from colon cancer
      patients (ranging from 14% to 27%). Our results on colon cancer illustrate both
      the complexity and the potential of the SEREX approach for analysis of the
      humoral immune response against human cancer.

PMID- 9610722
TI  - Dietary habits and stomach cancer in Shanghai, China.
AB  - Stomach cancer remains the second leading cancer in incidence in Shanghai, China,
      despite its decline over the past 2 decades. To clarify risk factors for this
      common malignancy, we conducted a population-based case-control study in
      Shanghai, China. Included in the study were 1,124 stomach cancer patients (age 20
      69) newly diagnosed in 1988-1989 and 1,451 controls randomly selected among
      Shanghai residents. Usual adult dietary intake was assessed using a comprehensive
      food frequency questionnaire. Adjusted odds ratios (ORs) and 95% confidence
      intervals (CIs) were estimated using logistic regression models. Risks of stomach
      cancer were inversely associated with high consumption of several food groups,
      including fresh vegetables and fruits, poultry, eggs, plant oil, and some
      nutrients, such as protein, fat, fiber and antioxidant vitamins. By contrast,
      risks increased with increasing consumption of dietary carbohydrates, with odds
      ratios (ORs) of 1.5 (95% confidence interval [CI] 1.1-2.1) and 1.9 (95% CI 1.3
      2.9) in the highest quartile of intake among men (p for trend=0.02) and women
      (p=0.0007), respectively. Similar increases in risk were associated with frequent
      intake of noodles and bread in both men (p=0.07) and women (p=0.05) after further
      adjustment for fiber consumption. In addition, elevated risks were associated
      with frequent consumption of preserved, salty or fried foods, and hot
      soup/porridge, and with irregular meals, speed eating and binge eating. No major
      differences in risk were seen according to subsite (cardia vs. non-cardia). Our
      findings add to the evidence that diet plays a major role in stomach cancer risk
      and suggest the need for further evaluation of risks associated with
      carbohydrates and starchy foods as well as the mechanisms involved.

PMID- 9610723
TI  - Risk for endometrial cancer in relation to occupational physical activity: a
      nationwide cohort study in Sweden.
AB  - Notwithstanding its biologic plausibility, the association between physical
      activity and endometrial cancer has been analyzed in only a few epidemiological
      studies. Retrospective assessment of exposure and small sample size often hampers
      interpretation of published data. We studied risk for endometrial cancer in
      relation to physical activity at work in a large cohort of Swedish women
      identified in the nationwide censuses in 1960 and 1970, with jobs that could be
      consistently classified into one of 4 levels of physical demands. Follow-up from
      1971 through 1989 was accomplished through record linkages. Multivariate Poisson
      regression models were used to estimate relative risk. The risk for endometrial
      cancer increased regularly with decreasing level of occupational physical
      activity (p for trend < 0.001), and was associated more strongly with activity in
      1970 than in 1960. In multivariate analyses, adjusted for age at follow-up, place
      of residence, calendar year of follow-up, and social class, the relative risk
      among women with the same physical activity level in 1960 and in 1970 was 30%
      higher for sedentary as compared with high/very high activity level; (p for
      trend=0.04). The protective effect of physical activity appeared to be confined
      to women aged 50 to 69, among whom sedentary work was associated with a 60%
      higher risk than that observed among women estimated to be physically most
      active. The excess seemed to disappear within 10 years after a change in physical
      activity level. Although confounding cannot be ruled out in our data,
      occupational physical activity appears to reduce the risk for endometrial cancer.

PMID- 9610724
TI  - Human Trop-2 is a tumor-associated calcium signal transducer.
AB  - Trop-2/EGP-1/GA733-1 is a recently identified cell surface glycoprotein highly
      expressed by human carcinomas. The cytoplasmic tail of Trop-2 possesses potential
      serine and tyrosine phosphorylation sites and a phosphatidyl-inositol binding
      consensus sequence. Thus, we investigated whether Trop-2 might be a functional
      signaling molecule. Using the fluorescent probe Fura-2, we assayed the
      cytoplasmic calcium levels in human cancer cells stimulated with anti-Trop-2 or
      control antibodies. Three anti-Trop-2 MAbs, Rs7-7G11, MOv16 and 162-46.2
      specifically induced a transient intracellular calcium level increment in up to
      40% of the experiments performed. Polyclonal antisera recognizing recombinant
      Trop-2 molecules possessed a much lower stimulation efficiency. The average
      latency of antibody-induced Ca2+ rise for OvCa-432 cells was 64+/-26 sec.
      Internal Ca2+ concentrations reached peaks of 190+/-24 nM vs. basal levels of
      61+/-4 nM and returned to baseline within 193+/-37 sec. Similar values were
      obtained in MCF-7 cells. For comparison, stimulation of P2-purinergic receptors
      on MCF-7 and OvCa-432 cells induced a Ca2+ rise in most cases, leading to average
      internal Ca2+ concentrations of 297+/-41 and 391+/-39 nM, respectively. Our
      findings show that Trop-2 transduces an intracellular calcium signal, are
      consistent with the hypothesis that it acts as a cell surface receptor and
      support a search for a physiological ligand.

PMID- 9610725
TI  - Establishment and characterization of three new breast-cancer cell lines.
AB  - We have established and characterized 3 new breast-cancer cell lines from pleural
      effusions of patients with advanced breast cancer. All 3 cell lines, designated
      IBEP-1, IBEP-2 and IBEP-3, showed typical ultrastructural characteristics of
      epithelial mammary tumor cells. Electron microscopy showed, among other
      characteristics, the presence of numerous microvilli, desmosomal junctions,
      intracytoplasmic duct-like vacuoles, well-developed endoplasmic reticulum and
      large nuclei. Immunohistochemical and biochemical studies revealed that the 3
      cell lines expressed cytokeratin, epithelial membrane antigen, CEA and CA 15-3,
      but all showed negative immunoreaction for vimentin. On the other hand, other
      antigens (LEU-M1, GCDFP 15, c-erbB-2) were expressed by some of the cell lines,
      but in a variable manner. Ploidy studies confirmed the neoplastic origin of the
      cell lines. The doubling times were 68 hr for IBEP-1, 29 hr for IBEP-2 and 39 hr
      for IBEP-3. Only IBEP-2 cells expressed estrogen receptors (ER+), which were down
      regulated after preincubation with E2, but they did not express progesterone
      receptors (PgR-). IBEP-1 and IBEP-3 cells were ER- but expressed PgR (PgR+). In
      these 2 cell lines, PgR were down-regulated after pre-incubation of the cells
      with progesterone (10(-8) M) for 24 hr. Estradiol (E2) increased the
      proliferation rate of IBEP-2 cells and progesterone increased the proliferation
      of IBEP-I and -3 cell lines. S.C. injection of the 3 IBEP cell lines into nude
      mice resulted in the growth of solid tumors between 11 and 16 weeks after
      inoculation. These cell lines could thus be new models for studying various
      aspects of the biology and the tumorigenicity of breast-cancer cells. A major
      interest of these new cell lines is that 2 of them were ER- and PgR+, which is an
      exceptional phenotypic feature. These 2 cell lines could be interesting models
      for studying the regulation of PgR and the effects of progestins and
      antiprogestins independently of the presence of ER.

PMID- 9610726
TI  - Estrogenic regulation of clusterin mRNA in normal and malignant endometrial
      tissue.
AB  - Clusterin is a heterodimeric, 80kDa, glycoprotein that is synthesized in a wide
      variety of tissues in response to a number of diverse stimuli, including hormone
      ablation. We have investigated the regulation of clusterin expression by
      estradiol and anti-estrogens in RUCA-I rat endometrial adenocarcinoma cells in
      vitro and in vivo. We have also compared clusterin expression in endometrial
      tumors and in normal uterine tissue. Estradiol treatment significantly increases
      the steady state mRNA levels of clusterin in RUCA-I cells cultured on a
      reconstituted basement membrane, with a maximal induction 24 hr after estradiol
      treatment. The inductive effects of estrogen on clusterin mRNA steady state
      levels in vitro are significantly more pronounced than the effects on fibronectin
      mRNA levels, an estrogen-repressed gene in RUCA-I. In vivo, induction of
      clusterin expression in primary and metastatic endometrial adenocarcinoma is also
      dependent on the presence of estradiol, in marked contrast to expression of
      clusterin in the normal endometrium of the same animals. These data suggest that
      clusterin mRNA expression in rat endometrial adenocarcinoma cells is tightly
      regulated by estrogens and anti-estrogens in vitro and in vivo, and that there is
      a complex mechanism of regulation of clusterin expression in the normal and
      cancerous endometrium.

PMID- 9610727
TI  - Preleukemia in long-term plasmacytoma-regressor mice.
AB  - Our previous results have indicated that mice whose plasmacytoma regressed
      following curative melphalan chemotherapy manifested various persistent
      immunohematological abnormalities including immunosuppression,
      myeloproliferation, as well as excessive production of and response to growth
      factors. Mice not bearing plasmacytoma treated with an identical dose of
      melphalan chemotherapy did not exhibit such abnormalities. In the present study
      we show that plasmacytoma-regressor mice (PRM) contain preleukemic cells which do
      not progress to leukemia in these mice. However, adoptive transfer of splenocytes
      originating in PRM to preirradiated but otherwise untreated syngeneic recipients
      resulted in the development of overt leukemia in these recipients. The presence
      of leukemia in the primary recipient mice was ascertained by blood counts as well
      as by spleen histology. Furthermore, splenocytes from the irradiated primary
      recipients adoptively transferred to non-irradiated secondary recipients caused
      leukemia formation in 100% of the secondary recipients. Sex chromosome analysis
      of the leukemic cells in the irradiated primary recipients clearly showed that
      they originated in the PRM donors. Two leukemic lines were established from
      leukemias developing in the secondary recipients and both expressed surface
      markers of hematopoietic progenitor cells as well as markers of T cells. We
      suggest that PRM could serve as an animal model to investigate development of
      chemotherapy-related leukemia in humans.

PMID- 9610728
TI  - Epstein-Barr virus-infected B cells of males with the X-linked
      lymphoproliferative syndrome stimulate and are susceptible to T-cell-mediated
      lysis.
AB  - Primary infection with the Epstein-Barr virus (EBV) results in fatal infectious
      mononucleosis in up to 70% of males affected by the X-linked lymphoproliferative
      syndrome (XLP). This rare disease is often associated with diverse natural killer
      (NK)-, B- and T-cell deficiencies. We describe experiments testing whether the B
      lymphocytes of affected males play a role in the pathogenesis of XLP due to a low
      susceptibility to T-cell-mediated immunity. Using reverse transcription
      polymerase chain reaction (RT-PCR) and immunohistochemistry we detected in these
      B cells the expression of viral proteins EBNA-1, EBNA-2, EBNA-3A, EBNA-3C, LMP-1
      and LMP-2A, which provide targets for cytotoxic T cells. Major histocompatibility
      complex (MHC) class I, MHC class II and the B7 costimulatory molecule were
      present on the cell surface. Accordingly, the EBV-infected B cells were lysed in
      51Cr-release assays by T lymphocytes sharing MHC determinants with the targets.
      This MHC-restricted and specific lysis was confirmed in competition experiments
      using MHC-specific monoclonal antibodies (MAbs) and synthetic peptides. XLP
      derived LCLs could also induce MHC class I-restricted memory and cytotoxic T
      lymphocytes. Thus, these XLP-derived B cells resembled normal LCIs in vitro with
      respect to induction of EBV-specific cytotoxic T cells (CTL), the ability to
      present EB viral antigens and the susceptibility to EBV-specific and MHC
      restricted CTL-mediated killing. The failure of the immune system to eliminate
      these virus-infected B cells in XLP is clearly not caused by a B-cell-specific
      defect.

PMID- 9610729
TI  - Induction of broad drug resistance in small cell lung cancer cells and its
      reversal by paclitaxel.
AB  - The H82 "variant" and the H69 "classic" small cell lung cancer (SCLC) cell lines
      were treated with low levels of epirubicin (69 and 14 nM) which caused little
      cell death but produced the H82/E8 and H69/E8 extended-multidrug resistant
      sublines. Both were resistant to drugs associated with multidrug resistance
      (MDR), and to chlorambucil (9.5- and 5.6-fold, respectively) and cisplatin (2.3-
      and 8.5-fold, respectively). There was increased expression of the multidrug
      resistance-associated protein (MRP1) in the H82/E8 subline while P-glycoprotein
      expression was not detected in any cells or sublines. Treatment of the H82 cells
      for 1 hr with 69 nM epirubicin increased MRP1-mRNA expression within 4 hr and
      this was associated with an increase in the resistance to epirubicin,
      chlorambucil, cisplatin and paclitaxel. Further, a 1 hr treatment with non
      cytotoxic doses of chlorambucil (2.5 microM), cisplatin (1.3 microM) or
      paclitaxel (13 nM), drugs not normally associated with MRP1-mediated MDR, also
      increased MRP1-mRNA expression in the H82 cells with paclitaxel causing the
      highest increase (4.5-fold). For chlorambucil treatment, this increased MRPI-mRNA
      expression was accompanied by increased drug resistance while paclitaxel
      treatment had no effect on drug resistance in the H82 cells. For the drug
      resistant H82/E8 subline, these drug treatments had no effect on the MRP1-mRNA
      expression and little effect on increasing the subline drug resistance. However,
      pretreatment with paclitaxel sensitised the H82/E8 subline to chlorambucil and
      cisplatin returning the subline to the sensitivity of the H82 cell line. We
      conclude that treatment with low levels of MDR and non-MDR drugs can induce
      extended-multidrug resistance in SCLC cells, a process that probably involves the
      co-ordinate upregulation of MRP1 and other resistance mechanisms. The results
      also suggest paclitaxel may have a role as a response modifier in the treatment
      of refractory SCLC.

PMID- 9610730
TI  - Design and testing of a new cisplatin form using a base material by combining
      poly-D,L-lactic acid and polyethylene glycol acid against peritoneal metastasis.
AB  - Microspheres containing cisplatin (CDDP) embedded in poly-d,l-lactic acid (PLA)
      and polyethylene glycol acid (CDDP-PPMS) were developed to improve treatment of
      malignant effusions. In vitro studies demonstrated that CDDP was released
      continuously for more than 4 weeks from CDDP-PPMS without initial burst. CDDP
      PPMS was compared with CDDP aqueous solution (CDDP-SOL) by i.p. administration in
      rats for 1) tissue distribution, 2) toxicity and 3) therapeutic effects against
      Yoshida sarcoma. We found that the CDDP concentration in the omentum was
      maintained at a higher level than in the CDDP-SOL group, while the particles of
      CDDP-PPMS were observed in the stomata of the omentum by electron microscopy.
      Concentrations of CDDP in the lung, liver, kidney and blood were lower in the
      CDDP-PPMS group than in the CDDP-SOL group. All rats given CDDP-PPMS containing <
      or = 28 mg/kg were alive, whereas in the CDDP-SOL group, all rats given > or = 16
      mg/kg died from side effects. The LD50 of CDDP-PPMS and CDDP-SOL were 32.8 and
      14.8 mg/kg, respectively. The survival of rats with peritoneal metastasis was
      better in the CDDP-PPMS group than in the CDDP-SOL group.

PMID- 9610732
TI  - Antisense phosphorothioate oligonucleotides specifically down-regulate cdc25B
      causing S-phase delay and persistent antiproliferative effects.
AB  - Cell cycle progression in mammalian cells is regulated by a family of cyclin
      dependent kinases (cdks) that are activated by a family of 3 cdc25 phosphatases:
      cdc25A, cdc25B and cdc25C. We examined the expression of mRNA and protein of all
      3 cdc25s during the HeLa cell cycle, and found that cdc25B protein has a unique
      and limited pattern of expression relative to other cdc25 homologs. Antisense
      oligonucleotides reduced cdc25B mRNA levels and dysregulated protein expression,
      while inhibiting S-phase progression in synchronized HeLa cells. Scrambled
      control oligonucleotides had no effect. Antisense oligonucleotides transfected in
      early G2-phase had no effect on cell cycle progression. A direct correlation
      between down-regulation of cdc25B and inhibition of thymidine incorporation was
      found using several oligonucleotides. Our results suggest a role for cdc25B in S
      phase and demonstrate that inhibition of cdc25B has persistent antiproliferative
      effects.

PMID- 9610731
TI  - Interleukin-10 gene transfer inhibits murine mammary tumors and elevates nitric
      oxide.
AB  - Transfection of cDNA for IL-10 into line 66.1 murine mammary tumor cells results
      in marked suppression of tumor growth and metastasis. Others have reported that
      nitric oxide has potent antitumor activity and IL-10 is known to regulate the
      inducible isoform of nitric oxide synthase (iNOS) expressed in macrophages. We
      identified nitric oxide production in mammary tumors as indicated by electron
      paramagnetic resonance detection of nitric oxide-hemoglobin (NO-Hb). IL-10
      expression resulted in elevated levels of NO-Hb in mammary tumors.
      Immunohistochemical examination of mammary tumors for iNOS protein revealed few
      positively staining cells in parental or control neo-transfected tumors but
      strong iNOS staining in all IL-10 transfected tumors, consistent with the NO-Hb
      data. To determine if mammary epithelial tumor cells themselves, express nitric
      oxide synthase activity, cultured tumor cells were treated with pro-inflammatory
      cytokines and nitrite accumulation was assessed in the conditioned medium. All IL
      10 producing cell lines accumulated uM concentrations of nitrite in response to
      short term (24 hr) cytokine stimulation. Cells not expressing IL-10 (parental and
      neo-transfectants) accumulated no nitrite under similar culture conditions. After
      longer stimulation (48 hr), parental and 66-neo cells accumulated lower amounts
      of nitrite. IL-10 gene transfer is associated with increased iNOS protein
      expression and enzymatic activity detected both in vitro and in vivo. Our
      findings suggest that the antimetastatic and antitumor activity of IL-10 is
      related to enhanced production of nitric oxide.

PMID- 9610733
TI  - Drug binding to P-glycoprotein is inhibited in normal tissues following SDZ-PSC
      833 treatment.
AB  - Rats were treated with daily injections of SDZ-PSC 833 (PSC) to study the
      interaction of this potent modulator of multidrug resistance (MDR) with P
      glycoprotein (P-gp) expressed in normal tissues. After 2 days of treatment, the
      level of P-gp expression, detected by Western blot analysis, was not modified in
      renal brush border membranes (BBMs) and brain capillaries. However, the amount of
      P-gp detected with the photoaffinity probe [125I]-arylazidoprazosin (IAAP) was
      decreased in both tissues, suggesting that the drug binding properties of P-gp
      were altered by PSC treatment. This effect was further characterized by treating
      rats with PSC for 10 days. Following these treatments, the amount of
      immunodetected P-gp was increased in renal BBMs and brain capillaries. However,
      no increase in P-gp expression was observed in photolabeling experiments,
      suggesting that induced P-gp was not functional. In vitro experiments performed
      with renal BBMs showed that the inhibition of P-gp photolabeling by cyclosporin A
      (CsA), verapamil and vinblastine could be reversed by performing washing steps to
      remove these drugs before incubating the samples with IAAP. However, the
      inhibition mediated by PSC was less reversible since photolabeling of P-gp
      remained inhibited following the washing steps. Pre-incubation of intact CHRC5
      cells with PSC, CsA and verapamil also inhibited P-gp photolabeling and increased
      rhodamine 123 accumulation. For PSC pre-treated samples, these effects were not
      completely reversed following washing, but were abolished for CsA and Ver pre
      treated samples. Our results suggest that PSC could block P-gp function by a
      different mechanism from that of CsA and verapamil, involving modification of the
      drug binding sites.

PMID- 9610734
TI  - Therapeutic efficacy and dose-limiting toxicity of Auger-electron vs. beta
      emitters in radioimmunotherapy with internalizing antibodies: evaluation of 125I-
      vs. 131I-labeled CO17-1A in a human colorectal cancer model.
AB  - Recent clinical results suggest that higher anti-tumor efficacy may be achieved
      with internalizing monoclonal antibodies (MAbs) at lower toxicity when labeled
      with Auger-electron, as compared to conventional beta-emitters. The aim of our
      study was to compare the toxicity and anti-tumor efficacy of the 125I-labeled
      internalizing MAb, CO17-1A, with its 131I-labeled form in a human colon cancer
      model in nude mice. Biodistribution studies were performed in nude mice bearing
      s.c. human colon cancer xenografts. For therapy, the mice were injected either
      with unlabeled 125I- or 131I-labeled C017-1A at equitoxic doses. Control groups
      were left untreated, were given a radiolabeled isotype-matched irrelevant
      antibody or a tumor-specific, but noninternalizing antibody. The maximum
      tolerated activities (MTD) of 131I-and 125I-CO17-1A without artificial support
      were 300 microCi and 3 mCi, respectively. Myelotoxicity was dose-limiting; bone
      marrow transplantation allowed for an increase of the MTD to 400 microCi of 131I
      17-1A, whereas the MTD of 125I-17-1A with bone marrow support had not been
      reached at 5 mCi. Whereas no significant therapeutic effects were seen with
      unlabeled C017-1A, tumor growth was retarded with 131I-CO17-1A. With the 125I
      label, however, therapeutic results were clearly superior. In contrast, no
      significant difference was observed in the therapeutic efficacy of the 131I- vs.
      125I-labeled, noninternalizing antibodies. Our data indicate a superiority of
      Auger-electron emitters, such as 125I, as compared to therapy with conventional
      beta-emitters with internalizing antibodies. The lower toxicity of Auger emitters
      may be due to the short path length of their low-energy electrons, which can
      reach the nuclear DNA only if the antibody is internalized (as is the case in
      antigen-expressing tumor tissue, but not in the stem cells of the red marrow).

PMID- 9610735
TI  - HT-1080 fibrosarcoma cell matrix degradation and invasion are inhibited by the
      matrix-associated serine protease inhibitor TFPI-2/33 kDa MSPI.
AB  - The urokinase-urokinase receptor system plays a dominant role in the degradation
      and invasion of extracellular matrix (ECM) by tumor cells. In this system,
      urokinase bound to its cell receptor converts plasminogen to plasmin, a broad
      spectrum serine protease that participates in the degradation and invasion of
      connective tissues by tumor cells. In this study, we evaluated whether these
      activities of plasmin are inhibited by a newly characterized human 32 kDa
      recombinant serine protease inhibitor called trypsin/tissue factor pathway
      inhibitor-2 (rTFPI-2). We found that rTFPI-2 dose-dependently inhibited fluid
      phase plasmin as well as plasmin generated on the ECM and/or the cell surface of
      HT-1080 fibrosarcoma cells. The degradation of radiolabeled matrix as well as
      Matrigel invasion by these tumor cells is also inhibited by rTFPI-2 in a dose
      dependent fashion. We have reported that rTFPI-2 is identical to 33 kDa
      extracellular matrix-associated serine protease inhibitor (33 kDa MSPI), whereas
      the 31 and 27 kDa MSPIs are under-glycosylated forms of the 33 kDa MSPI. We
      therefore evaluated the ability of MSPIs from the ECM of dermal fibroblasts to
      inhibit plasmin and found that the plasmin activity was effectively blocked by
      the MSPIs. We have also evaluated whether the HT-1080 cells synthesize and
      secrete the MSPIs and found that the synthesis and secretion of the MSPIs was
      undetectable in these cells. Collectively, our results suggest that rTFPI-2/33
      kDa MSPI inhibits plasmin on the tumor cell and ECM surfaces as well as the
      degradation and invasion of matrix by HT-1080 fibrosarcoma cells.

PMID- 9610736
TI  - Induction of p53 and melanoma cell death is reciprocal with down-regulation of
      E2F, cyclin D1 and pRB.
AB  - Tumor-suppressor-gene products such as p53 and retinoblastoma (Rb) play an
      important role as negative regulators of cell-cycle progression, which is
      reciprocally favored by the availability of cyclin D1 and the E2F transcription
      factor. We now show that UV irradiation of B16 melanoma after prior exposure to
      the radiation sensitizer, bromodeoxyuridine (BUdR) leads to induction of p53 and
      DNA fragmentation, and concomitant decreases in Rb, E2F, cyclin D1, and cell
      viability, with no comparable effects on irradiated unsensitized cells. Our data
      suggest that over-expression of p53 correlates with down-regulation of E2F,
      cyclin D1 in inducing apoptosis.

PMID- 9610737
TI  - Targeting T cells against brain tumors with a bispecific ligand-antibody
      conjugate.
AB  - High-affinity receptors expressed on the surface of some tumors can be exploited
      by chemically conjugating the ligand for the receptor and an antibody against
      immune effector cells, thus redirecting their cytolytic potential against the
      tumor. Ovarian carcinomas and some brain tumors express the high-affinity folate
      receptor (FR). In this report, a transgenic mouse model that generates
      endogenously arising choroid plexus tumors was used to show that folate/anti-T
      cell receptor antibody conjugates can direct infiltration of T cells into solid
      brain tumor masses. An engineered single-chain Fv form of the anti-T-cell
      receptor antibody KJ16 was conjugated with folate, to produce a bispecific agent
      that was substantially smaller than most previously characterized bispecific
      antibodies. Folate conjugation to the antibody increased T-cell infiltration into
      the tumors by 10- to 20-fold, and significantly prolonged survival of the mice.

PMID- 9610738
TI  - Phenotypic diversity in human fibroblasts from myelometaplasic and non
      myelometaplasic hematopoietic tissues.
AB  - Fibroblasts from a variety of tissues interact with and influence the behavior of
      the cell types they are associated with by producing specific proteins that
      mediate these interactions. Thus, it is not surprising that fibroblasts have been
      shown to differ phenotypically and functionally depending on the tissue they are
      isolated from and its physiologic state. To study fibroblasts of hematopoietic
      tissues, cultures were established from human normal bone marrow (BM), and from
      non-myelometaplasic (NS) and myelometaplasic spleen (MMS) tissues and analyzed
      for phenotypic characteristics. The results are summarized as follows: (1)
      cytoskeletal elements: virtually all the MMS fibroblasts were stained positively
      for alpha-sm-actin while only a small fraction of BM and of NS fibroblasts were
      positive for this antigen; (2) extracellular matrix elements: MMS fibroblasts
      stained positively for ED-B fibronectin and tenascin while the other 2 fibroblast
      cell types did not; (3) cell surface molecules: NS and MMS fibroblasts expressed
      significantly higher levels of ICAM-1, VLA-4 and CD9 than BM fibroblasts.
      Moreover, MMS fibroblasts showed a higher expression of ICAM-1 and VLA-4 than NS
      fibroblasts; and (4) cytokines: IL-II, RANTES and MIP-1alpha were produced in
      higher amounts by BM than by NS fibroblasts. Conversely, production of GM-CSF,
      SCF, M-CSF and MCP-1alpha was elevated in NS compared with BM fibroblasts. The
      production of these cytokines was generally reduced in MMS cells. Overall, our
      results demonstrate that phenotypic characteristics can be identified to
      distinguish fibroblasts from normal and pathologic hematopoietic tissues. Such
      phenotypic characteristics suggest functional differences of each type of
      fibroblast in their influence on the blood cells with which they are associated.

PMID- 9610739
TI  - A unitary model for involutional osteoporosis: estrogen deficiency causes both
      type I and type II osteoporosis in postmenopausal women and contributes to bone
      loss in aging men.
AB  - We propose here a new unitary model for the pathophysiology of involutional
      osteoporosis that identifies estrogen (E) deficiency as the cause of both the
      early, accelerated and the late, slow phases of bone loss in postmenopausal women
      and as a contributing cause of the continuous phase of bone loss in aging men.
      The accelerated phase in women is most apparent during the first decade after
      menopause, involves disproportionate loss of cancellous bone, and is mediated
      mainly by loss of the direct restraining effects of E on bone cell function. The
      ensuing slow phase continues throughout life in women, involves proportionate
      losses of cancellous and cortical bone, and is associated with progressive
      secondary hyperparathyroidism. This phase is mediated mainly by loss of E action
      on extraskeletal calcium homeostasis which results in net calcium wasting and
      increases in the level of dietary calcium intake required to maintain bone
      balance. Because elderly men have low circulating levels of both bioavailable E
      and bioavailable testosterone (T) and because recent data suggest that E is at
      least as important as T in determining bone mass in aging men, E deficiency may
      also contribute substantially to the continuous bone loss of aging men. In both
      genders, E deficiency increases bone resorption and may also impair a
      compensatory increase in bone formation. For the most part, this unitary model is
      well supported by observational and experimental data and provides plausible
      explanations to traditional objections to a unitary hypothesis.

PMID- 9610740
TI  - Estrogens and postmenopausal osteoporosis: was Albright right after all?

PMID- 9610741
TI  - Combination of interleukin-6 and soluble interleukin-6 receptors induces
      differentiation and activation of JAK-STAT and MAP kinase pathways in MG-63 human
      osteoblastic cells.
AB  - Studies on the role of interleukin-6 (IL-6) in bone metabolism have been
      accumulating. However, its effects on osteoblasts are still unclear because the
      results are conflicting depending on the study models employed. We reasoned that
      these conflicting data are due to variable expression levels of membrane-bound IL
      6 receptors (IL-6Rs). In the present study, we found that IL-6 in combination
      with soluble IL-6R (sIL-6R) consistently caused a marked elevation of alkaline
      phosphatase and a decrease in proliferation in the human osteoblastic cell line
      MG-63, which expressed no detectable membrane-bound IL-6R and failed to respond
      to IL-6. These effects of IL-6/sIL-6R were blocked by neutralizing antibodies to
      the IL-6 signal transducer gp130, suggesting an involvement of IL-6 signaling in
      the elicitation of the effects of IL-6/sIL-6R. Upon stimulation with IL-6/sIL-6R,
      the gp130, cytoplasmic Janus kinases JAK1 and JAK2 were tyrosine phosphorylated.
      Moreover, signal transducers and activators of transcription STAT1 and STAT3 were
      also tyrosine phosphorylated, translocated to the nucleus, and bound to the
      putative STAT-binding DNA elements. In addition, mitogen-activated protein (MAP)
      kinase was also activated in response to IL-6/sIL-6R These data demonstrate that
      sIL-6R may enhance the responsiveness of MG-63 cells to IL-6. Thus, IL-6 in
      collaboration with sIL-6R may modulate differentiation and proliferation of
      osteoblastic cells, presumably by activating two distinct signaling pathways of
      JAK-STAT and MAP kinase.

PMID- 9610742
TI  - Alendronate/interleukin-1beta cotreatment increases interleukin-6 in bone and UMR
      106 cells: dose dependence and relationship to the antiresorptive effect of
      alendronate.
AB  - Aminobisphosphonates inhibit bone resorption but have been shown to elicit acute
      phase-like elevations in interleukin-6 (IL-6) in bone in vitro. The current
      studies were carried out to determine the relationship between the antiresorptive
      effects of the aminobisphosphonate alendronate and its effects on IL-6.
      Resorption was elicited in cultured 19-day fetal rat limb bones by 72 h treatment
      with interleukin-1beta (IL-1beta). Bone mass was quantitated at the end of the
      culture period to assess resorption. IL-6 was determined by bioassay (7TD1 cell
      proliferation). IL-1beta (18 and 180 pM) stimulated bone resorption and increased
      IL-6. Alendronate (70 microM) inhibited the IL-1beta-stimulated resorption.
      Alendronate alone did not affect IL-6 production by the bones. The IL-6
      production from bones stimulated with 18 pM IL-1beta was not significantly
      affected by alendronate, but the IL-6 production from bones stimulated with 180
      pM IL-1beta plus alendronate (21 and 70 microM) was higher than with IL-1beta
      alone. Indomethacin (1 mM) inhibited the IL-6 increase elicited by 180 pM IL
      1beta and the enhanced IL-6 production elicited by cotreatment with IL-1beta and
      alendronate. Since bone cultures contain multiple cell types, further experiments
      were carried out to determine whether alendronate could increase IL-1beta
      stimulated IL-6 production in an osteoblast cell line, UMR-106. Alendronate alone
      did not affect IL-6 in UMR-106 cells. Alendronate (70 microM) in combination with
      IL-1beta (180, 1.8, or 8 nM), or 7 microM alendronate, in combination with 8 nM
      IL-1beta, significantly increased IL-6 in 48 h cell cultures. The results from
      the bone organ cultures show that alendronate can enhance IL-6 production
      elicited by higher concentrations of the cytokine IL-1beta in bone, but that this
      effect on IL-6 does not prevent the inhibitory actions of alendronate on bone
      resorption. The results with the UMR106 cells indicate that one cellular site at
      which this enhancement of IL-6 production can occur is the osteoblast.

PMID- 9610743
TI  - Osteoblast programmed cell death (apoptosis): modulation by growth factors and
      cytokines.
AB  - Once osteoblasts have completed their bone-forming function, they are either
      entrapped in bone matrix and become osteocytes or remain on the surface as lining
      cells. Nonetheless, 50-70% of the osteoblasts initially present at the remodeling
      site cannot be accounted for after enumeration of lining cells and osteocytes. We
      hypothesized that the missing osteoblasts die by apoptosis and that growth
      factors and cytokines produced in the bone microenvironment influence this
      process. We report that murine osteoblastic MC3T3-E1 cells underwent apoptosis
      following removal of serum, or addition of tumor necrosis factor (TNF), as
      indicated by terminal deoxynucleotidyl transferase-mediated dUTP-nick end
      labeling and DNA fragmentation studies. Transforming growth factor-beta and
      interleukin-6 (IL-6)-type cytokines had antiapoptotic effects because they were
      able to counteract the effect of serum starvation or TNF. In addition, anti-Fas
      antibody stimulated apoptosis of human osteoblastic MG-63 cells and IL-6-type
      cytokines prevented these changes. The induction of apoptosis in MG-63 cells was
      associated with an increase in the ratio of the proapoptotic protein bax to the
      antiapoptotic protein bcl-2, and oncostatin M prevented this change. Examination
      of undecalcified sections of murine cancellous bone revealed the presence of
      apoptotic cells, identified as osteoblasts by their proximity to osteoid seams
      and their juxtaposition to cuboidal osteoblasts. Assuming an osteoblast life span
      of 300 h and a prevalence of apoptosis of 0.6%, we calculated that the fraction
      that undergo this process in vivo can indeed account for the missing osteoblasts.
      These findings establish that osteoblasts undergo apoptosis and strongly suggest
      that the process can be modulated by growth factors and cytokines produced in the
      bone microenvironment.

PMID- 9610744
TI  - Inorganic polyphosphate in human osteoblast-like cells.
AB  - Significant amounts of inorganic polyphosphates and of polyphosphate-degrading
      exopolyphosphatase activity were detected in human mandibular-derived osteoblast
      like cells. The amount of both soluble and insoluble long-chain polyphosphate in
      unstimulated osteoblast-like cells was higher than in human gingival cells,
      erythrocytes, peripheral blood mononuclear cells, and human blood plasma. The
      cellular content of polyphosphate in osteoblast-like cells strongly decreased
      after a combined treatment of the cells with the stimulators of osteoblast
      proliferation and differentiation, dexamethasone, beta-glycerophosphate,
      epidermal growth factor, and ascorbic acid. The amount of soluble long-chain
      polyphosphate, but not the amount of insoluble long-chain polyphosphate, further
      decreased after an additional treatment with 1alpha,25-dihydroxyvitamin D3
      (1,25(OH)2D3). The decrease in polyphosphate content during treatment with
      dexamethasone, beta-glycerophosphate, epidermal growth factor, and ascorbic acid
      was accompanied by a decrease in exopolyphosphatase, pyrophosphatase, and
      alkaline phosphatase activity. However, additional treatment with 1,25(OH)2D3
      resulted in an increase in these enzyme activities. Osteoblast-like cell
      exopolyphosphatase activity and exopolyphosphatase activity in yeast, rat
      tissues, and human leukemia cell line HL60 were inhibited by the bisphosphonates
      etidronate and, to a lesser extent, clodronate and pamidronate. From our results,
      we assume that inorganic polyphosphate may be involved in modulation of the
      mineralization process in bone tissue.

PMID- 9610745
TI  - Collagen Ialpha1 Sp1 polymorphism, bone mass, and bone turnover in healthy French
      premenopausal women: the OFELY study.
AB  - Bone mineral density (BMD) is under strong genetic control. Recent work has
      suggested that a polymorphism affecting an Sp1 binding site in the collagen I
      (COLI) A1 gene is associated with BMD and vertebral fracture in postmenopausal
      women. We analyzed this polymorphism in relation to BMD and bone turnover in 220
      healthy premenopausal women aged 31-57 years. There were 61% SS homozygotes, 35%
      Ss heterozygotes, and 4% ss homozygotes, genotype frequencies similar to those
      previously reported in other Caucasian populations. Women in the three genotype
      groups were matched for age, body weight, physical activity, smoking habits, and
      oral contraceptive use, but height was greatest in the SS group and lowest in the
      ss group (p = 0.03). Between-group comparisons by analysis of variance (ANOVA)
      showed that COLI A1 genotype was significantly associated with spine BMD (p =
      0.05), total body BMD (p = 0.046), and total body bone mineral content (BMC) (p =
      0.02), but the differences between extreme genotypes were small (4, 5, and 10%,
      for spine BMD, total body BMD, and total body BMC, respectively). After
      adjustment for height, the differences between genotypes decreased and were no
      longer significant by ANOVA (p = 0.08, 0.17, and 0.33 for spine BMD, total body
      BMD, and total body BMC). Furthermore, no significant difference between
      genotypes was observed for femoral neck, trochanter, Ward's triangle, or forearm
      BMD. COLI A1 genotype was associated with serum C-terminal extension propeptide
      of type I collagen (p = 0.04), with lowest levels in ss individuals, but not with
      any other marker of bone formation (osteocalcin, alkaline phosphatase, and type I
      collagen N-terminal extension propeptide) or bone resorption (urinary excretion
      of type I collagen C and N telopeptide breakdown products). The COLI A1 Sp1
      polymorphism is associated with height, peak total body BMD and BMC, and spine
      BMD. The genotype-specific differences account for only a small proportion of
      variance in BMD at these sites and are not significant after adjustment for
      height, suggesting that part of the effect on bone mass may be due to differences
      in body size. Our data support the view that COLI A1 may be a candidate gene for
      regulation of bone mass, but our results must be treated with caution, in view of
      the small number of ss individuals, and will require confirmation in larger
      studies.

PMID- 9610746
TI  - Expression of the thrombin receptor in developing bone and associated tissues.
AB  - Thrombin, a serine protease with a central role in thrombosis and hemostasis, is
      also a specific agonist for a variety of cellular responses in osteoblasts and
      stimulates bone resorption in organ culture. Cultured osteoblast-like cells
      express the proteolytically activated thrombin receptor, but the significance of
      this finding in vivo remains unknown. Immunohistochemistry was used to
      investigate the normal tissue distribution of the proteolytically activated
      thrombin receptor in developing rat bones and associated tissues. In hind limbs,
      the receptor was first observed on embryonic day 16 and became more abundant
      within the limb as gestation progressed. Thrombin receptor staining was detected
      on osteoblasts, macrophages, muscle cells, and endothelial cells, but not
      osteoclasts. Similarly, osteoblasts in developing calvariae stained positively
      for the thrombin receptor. The pattern of receptor expression by primary
      osteoblast cultures and freshly isolated macrophages and osteoclasts corresponded
      to that observed in vivo. The observed pattern of thrombin receptor expression in
      bone cells supports the hypothesis that cell-mediated thrombin-induced bone
      resorption is mediated by osteoblasts.

PMID- 9610747
TI  - Vascular pericytes express osteogenic potential in vitro and in vivo.
AB  - At postconfluence, cultured bovine pericytes isolated from retinal capillaries
      form three-dimensional nodule-like structures that mineralize. Using a
      combination of Northern and Southern blotting, in situ hybridization, and
      immunofluorescence we have demonstrated that this process is associated with the
      stage-specific expression of markers of primitive clonogenic marrow stromal cells
      (STRO-1) and markers of cells of the osteoblast lineage (bone sialoprotein,
      osteocalcin, osteonectin, and osteopontin). To demonstrate that the formation of
      nodules and the expression of these proteins were indicative of true osteogenic
      potential, vascular pericytes were also inoculated into diffusion chambers and
      implanted into athymic mice. When recovered from the host, chambers containing
      pericytes were found reproducibly to contain a tissue comprised of cartilage and
      bone, as well as soft fibrous connective tissue and cells resembling adipocytes.
      This is the first study to provide direct evidence of the osteogenic potential of
      microvascular pericytes in vivo. Our results are also consistent with the
      possibility that the pericyte population in situ serves as a reservoir of
      primitive precursor cells capable of giving rise to cells of multiple lineages
      including osteoblasts, chondrocytes, adipocytes, and fibroblasts.

PMID- 9610748
TI  - The relationship between three-dimensional connectivity and the elastic
      properties of trabecular bone.
AB  - A finite-element model was used to explore the relationship between connectivity
      density and the elastic modulus of trabecular bone. Six cubic specimens of
      trabecular bone, three prepared from human distal radii and three from L1
      vertebrae, were imaged with synchrotron microtomography. The three-dimensional
      images were reconstructed into binary volumes of mineralized bone and soft
      tissue, and incorporated into the finite-element model. The relationship between
      three-dimensional connectivity and elastic modulus was explored by uniform
      thinning (atrophy) and thickening (recovery) of the trabecular bone. Though no
      functional relationship was found between connectivity and elastic modulus, there
      was a linear relationship, after a full cycle of atrophy and recovery, between
      the loss of elastic modulus and the overall loss of connectivity. The results
      indicate that recovery of mechanical function depends on preserving or restoring
      trabecular connectivity.

PMID- 9610749
TI  - Colony-stimulating factor-1 stimulates the fusion process in osteoclasts.
AB  - Colony-stimulating factor-1 (CSF-1), also called macrophage colony-stimulating
      factor, is required for growth, differentiation, activation, and survival of
      cells of the mononuclear phagocytic system. This cytokine has been shown to be
      essential for osteoclast development as well as for inducing both proliferation
      and differentiation of osteoclast progenitors. It also sustains survival of
      mature osteoclasts and stimulates spreading and migration of these cells. In the
      present in vitro study, the formation of large tartrate-resistant acid
      phosphatase (TRAP)-positive cells with a high number of nuclei was observed when
      osteoclasts isolated from rat long bones were incubated with CSF-1. These large
      cells, cultured on plastic, bind calcitonin and form F-actin along the edges of
      the cells. Fusion to such large TRAP-positive multinucleated cells in the
      presence of CSF-1 and the formation of pits were also observed on dentine slices.
      Quantitative data obtained from cultures on plastic demonstrated that the number
      of osteoclasts slightly increased in the course of 72 h in the presence of 250 pM
      CSF-1, whereas it decreased rapidly after 24 h in the absence of CSF-1, which
      confirms that this cytokine is required for the survival of osteoclasts. The
      number of nuclei per osteoclast was maximal after 16 h of incubation with CSF-1,
      namely twice the value found in the absence of CSF-1. The maximal effect of the
      cytokine on the fusion process was observed at a concentration of 250 pM. A
      calculation of the medians of the average frequency of nuclei distribution per
      osteoclast resulted in four nuclei per osteoclast in the absence and six in the
      presence of CSF-1. Genistein and herbimycin A, inhibitors of tyrosine kinases,
      inhibited the fusion induced by CSF-1. The data suggest that CSF-1 induces
      osteoclast fusion and that tyrosine kinase(s) are involved in this process. The
      fusion process may continue throughout the entire life of an osteoclast.

PMID- 9610750
TI  - Estrogen via the estrogen receptor blocks cAMP-mediated parathyroid hormone (PTH)
      stimulated osteoclast formation.
AB  - Several lines of evidence indicate that estrogen inhibits parathyroid hormone
      (PTH)-induced bone resorption in vivo and in vitro. However, its precise
      mechanism remains unknown. The present study was performed to investigate whether
      osteoclast precursor cells possess the receptors for PTH/PTH-related protein
      (PTHrP) and/or estrogen and to clarify the mechanism by which estrogen affects
      PTH-induced osteoclast-like cell (Ocl) formation. The polymerase chain reaction
      (PCR) product corresponding in size to the mouse PTH/PTHrP receptor cDNA was
      detected in mouse hemopoietic blast cells supported by granulocyte-macrophage
      colony-stimulating factor (GM-CSF) as well as in osteoblastic MC3T3-E1 cells. The
      nucleotide sequence of the PTH/PTHrP receptor PCR product of hemopoietic blast
      cells was found to be 95.4% identical to that of PTH/PTHrP receptor cDNA of rat
      osteoblastic ROS cells. The PCR product corresponding in size to the mouse
      estrogen receptor cDNA was detected in mouse hemopoietic blast cells supported by
      GM-CSF as well as in MC3T3-E1 cells. The nucleotide sequence of the estrogen
      receptor PCR product of hemopoietic blast cells was completely identical to that
      of mouse estrogen receptor cDNA. 17Beta-estradiol (17beta-E2) but not 17alpha-E2
      dose dependently antagonized Ocl formation stimulated by human (h) PTH(1-34) at a
      minimal effective concentration of 10(-10) M in the hemopoietic blast cell
      culture. 17Beta-E2 also significantly inhibited Ocl formation stimulated by 10(
      8) M hPTHrP(1-34), while it did not affect 1,25-dihydroxyvitamin D3-induced Ocl
      formation. However, 10(-8) M 17beta-E2 significantly inhibited Ocl formation
      stimulated by dibutyryladenosine cAMP (10(-4) M) and Sp-cAMPS (10(-4) M), an
      activator of cAMP-dependent protein kinase (PKA) as well as forskolin (10(-5) M).
      In contrast, 17beta-E2 did not affect Ocl formation by either phorbol myristate
      acetate (10(-7) M), an activator of protein kinase C (PKC), or A23187 (10(-7) M),
      a calcium ionophore. The pretreatment with 17beta-E2 significantly inhibited Ocl
      formation induced by the combined treatment with PTH and PKC inhibitors (H7 or
      staurosporine), while it did not affect Ocl formation stimulated by the combined
      treatment with PTH and Rp-cAMPS, a PKA inhibitor. The present data indicate that
      estrogen inhibits PTH-stimulated Ocl formation by directly acting on hemopoietic
      blast cells, possibly through blocking a PKA pathway but not a calcium/PKC
      pathway.

PMID- 9610752
TI  - Peripheral quantitative computed tomography in human long bones: evaluation of in
      vitro and in vivo precision.
AB  - Despite the excellent performance in clinical practice and research, the dual
      energy X-ray absorptiometry is restricted by the inherent planar nature of the
      measurement and the inability to discriminate between trabecular and cortical
      components of bone. Recently, a new peripheral tomographic scanner
      (Norland/Stratec XCT 3000) was introduced for versatile measurements of human
      long bone characteristics in vivo, including trabecular and cortical density (TrD
      and CoD, respectively), respective cross-sectional areas (TrA and CoA), bone
      strength index (BSI), and bone mineral content (BMC). We evaluated the technical
      performance of the scanner using different phantoms and determined the in vivo
      precision of the above-noted applications by measuring twice several sites of
      upper and lower limbs of 19 and 36 volunteers aged 23-60 years. The bone scans
      were performed, with intermediate positioning of the subject, at two different
      anatomic sites of the forearm, three sites of the upper arm, three sites of the
      shank, and two sites of the thigh, with the respective skeletal sites
      representing different bone compositions and sizes. According to phantom
      measurements, the XCT 3000 appeared to be a highly linear, stable, and precise
      (coefficient of variation [CV] about 0.2%) system in vitro. The soft tissue
      thickness, however, had a linear effect on density values and a nonlinear effect
      on BMC, whereas the effect on cross-sectional area was marginal. The in vivo root
      mean square CV (CVrms) values for the long bone ends ranged from 0.9% (distal
      tibia) to 2.7% (distal femur) for TrD, from 1.8% (distal femur) to 7.6% (distal
      radius) for TrA, from 2.0% (distal tibia) to 6.8% (proximal tibia) for CoD, from
      1.8% (distal femur) to 4.9% (proximal tibia) for CoA, and from 4.2% (distal
      tibia) to 7.7% (distal radius) for BSI. The corresponding CVrms values for the
      long bone shafts ranged from 0.5% (midshaft of humerus) to 1.4% (midshaft of
      fibula) for CoD, from 1.7% (midshaft of tibia) to 4.6% (proximal shaft of
      humerus) for CoA, and from 2.5% (midshaft of tibia) to 7.5% (proximal shaft of
      humerus) for BSI. There was no interoperator effect on precision. This study
      provided, for the first time, independent precision data for the new XCT 3000
      peripheral quantitative computed tomography (pQCT) scanner in various
      applications of human long bones (radius, ulna, humerus, tibia, fibula, and
      femur) and gave practical guidelines and procedures on how to employ this
      versatile method in clinical and research applications. The technical performance
      of the tested system was excellent and it allowed, with a low radiation dose,
      precise in vivo evaluation of trabecular and cortical density, cross-sectional
      area, and BMC of selected skeletal sites. The potential effect of the soft tissue
      thickness on density and mineral content values need to be recognized. The pQCT
      measurement seems to be useful in supplementing the integral, planar DXA data and
      obviously opens new possibilities for clinical practice and research.

PMID- 9610751
TI  - Evidence that ibuprofen antagonizes selective actions of estrogen and tamoxifen
      on rat bone.
AB  - Studies were performed to determine if the nonsteroidal anti-inflammatory drug
      ibuprofen alters bone and mineral metabolism in female rats. In experiment 1,
      four groups of growing rats underwent either sham operation or ovariectomy (OVX).
      One week later, controlled-release pellets with ibuprofen or placebo were
      implanted subcutaneously at the back of the neck. Following 3 weeks of treatment,
      rats were sacrificed and blood and bone samples were removed for serum assays and
      histomorphometric analysis. Body growth rate and the static cortical bone
      measurements made at the tibial diaphysis did not change in response to OVX. OVX,
      however, did increase radial bone growth, lowered serum 17beta-estradiol, reduced
      uterine weight, and decreased the cancellous bone area of the tibial metaphysis
      in the rats. Ibuprofen did not alter serum 17beta-estradiol or uterine weight but
      reduced radial bone growth as well as cancellous bone area of the tibial
      metaphysis in both sham-operated and OVX animals. In experiments 2 and 3, we
      tested the influence of ibuprofen on the effects of the tissue-selective estrogen
      agonist tamoxifen and of exogenous 17beta-estradiol in the OVX rat. Ibuprofen
      completely blocked the effects of tamoxifen and partially blocked the effects of
      17beta-estradiol to prevent cancellous osteopenia. In contrast, ibuprofen did not
      influence the effects of tamoxifen and 17beta-estradiol to reduce radial bone
      growth. Besides the skeletal effects, ibuprofen suppressed estrogen-induced
      uterine growth. Our data suggest that ibuprofen blocks selective estrogen
      receptor-mediated activities in the rat.

PMID- 9610753
TI  - Accretion of bone mass and strength with parathyroid hormone prior to the onset
      of estrogen deficiency can provide temporary beneficial effects in skeletally
      mature rats.
AB  - Intermittent administration of parathyroid hormone (PTH) has been shown to be an
      anabolic agent for animal and human skeletons. In previous studies, PTH has been
      used concurrent with, or subsequent to, the onset of bone loss. However, it is
      entirely possible that PTH may be used as an anabolic agent in a situation where
      there is stable skeletal remodeling. Increasing bone mass at this time might
      confer long-lasting beneficial effects when bone loss begins, for example,
      subsequent to the loss of ovarian function. To test this hypothesis, we evaluated
      the effects of administering rat PTH(1-34) (80 microg/kg/day, subcutaneously
      [s.c.]) to 6-month-old rats for a 2-week period prior to ovariectomy, and
      followed the natural occurrence of bone loss over a 14-week period. To determine
      the effects of estrogen intervention on bone gained by PTH treatment, one group
      was repleted with 17beta-estradiol (10 microg/kg/day via s.c. implant). Serial
      measurements of bone mass in vivo at the distal femur were obtained at 2-week
      intervals using dual-energy X-ray absorptiometry, while histologic and mechanical
      strength data were obtained from excised proximal tibiae and distal femurs after
      sacrifice. Two weeks of PTH treatment resulted in an increase of bone mineral
      density (BMD), mechanical strength, and cancellous bone volume (CnBV/TV). Four
      weeks after PTH withdrawal, significant residual beneficial effects on BMD and
      strength, irrespective of ovarian status, were observed. However, 14 weeks after
      PTH withdrawal, although there were still residual effects on CnBV/TV in
      ovariectomized animals pretreated with PTH, the PTH effects on BMD and mechanical
      strength had been lost. Estradiol repletion during the rapid bone loss phase
      following ovariectomy prevented the reduction in BMD associated with either
      ovariectomy or PTH withdrawal. Our results suggest that: treatment of rats with
      PTH prior to ovariectomy produces an increase in BMD and strength, these
      beneficial effects extend for a period of at least three times the treatment
      duration, the BMD that is lost when PTH is discontinued equates to the amount
      accrued during the PTH treatment, estrogen replacement can be used to maintain
      the bone gained as a result of PTH treatment.

PMID- 9610754
TI  - Serum levels of insulin-like growth factor binding proteins (IGFBP)-4 and -5
      correlate with bone mineral density in growth hormone (GH)-deficient adults and
      increase with GH replacement therapy.
AB  - Adults with growth hormone deficiency (GHD) exhibit low bone mineral density
      (BMD) which improves by growth hormone (GH) replacement therapy. The insulin-like
      growth factor (IGF) system has an established role in mediating the effects of GH
      on bone and IGF binding proteins (IGFBP)-4 and IGFBP-5 have been shown to
      modulate the effects of IGFs in bone. Therefore, we studied serum levels of IGFBP
      4 and IGFBP-5 and their relationship to serum levels of bone biochemical markers
      and BMD in adults with GH deficiency (GHD) before and during GH therapy. Serum
      levels of IGFBP-5 and IGFBP-4 were measured on samples from 20 patients (11
      males) 22-57 years of age. All had IGF-I serum values below -2 standard deviation
      score. The first 6 months were placebo controlled and all received 3 years of
      active treatment with the mean dose 0.23 +/- 0.01 IU/kg/week divided into daily
      subcutaneous injections. Serum IGFBP-5 levels in GHD adults were low at baseline
      and positively related to total body, femoral neck, trochanter, and Ward's
      triangle BMD (r = 0.471, 0.549, 0.462, and 0.470, respectively, p < 0.05). The
      mean serum IGFBP-5 level increased by about 2-fold within 3 months after the
      initiation of GH therapy and was correlated with serum IGF-I (r = 0.719, 0.801,
      and 0.722 before and after 18 and 36 months, respectively,p < 0.001). A positive
      correlation between serum IGFBP-5 levels and lumbar spine BMD was found during GH
      treatment but not before. The percentage increase of serum IGFBP-5 after GH
      therapy showed a positive correlation with the percentage increase of total
      alkaline phosphate activity (r = 0.347 p < 0.05). In contrast to IGFBP-5, serum
      IGFBP-4 levels were positively related to body mass index (r = 0.607, p < 0.01).
      Baseline serum IGFBP-4 levels also correlated with total body, femoral neck,
      trochanter, and Ward's triangle BMD (r = 0.502, 0.590, 0.612, and 0.471,
      respectively,p < 0.05). The mean serum IGFBP-4 level was increased by 25% within
      3 months after initiation of GH therapy and did not correlate with serum IGF-I
      levels. Although the above findings are consistent with the idea that GH-induced
      changes in serum IGFBP-5 and IGFBP-4 levels may in part mediate the anabolic
      effects of GH on bone tissue in adults with GHD, further studies are needed to
      establish the cause and effect relationship.

PMID- 9610755
TI  - The side-to-side differences of bone mass at proximal femur in female rhythmic
      sports gymnasts.
AB  - This cross-sectional study examined the side-to-side differences of the bone
      mineral density (BMD) at proximal femora in female rhythmic sports gymnasts
      (RSGs). The hypothesis on which the study is based is that gymnasts use a
      different leg in take-off (left leg) and in landing (right leg) and therefore
      differ in the loading for the left and right legs. The gymnasts made up two
      groups: the regular group, which consisted of 15 regular players who had trained
      for about 28 h/week, and the substitutes group, which consisted of 8 substitute
      players who had trained for about 12 h/week. The control group consisted of 10
      nonathletic college women who had not participated in any kind of regular sports
      activity. BMD (g/cm2) was measured in three hip sites using the XR-26 dual-energy
      X-ray absorptiometer scanner. Muscle strength at knee extensors (EXT) and flexors
      (FLX) was examined using an isokinetic dynamometer (CYBEX6000), and the vertical
      ground reaction force was determined with a force platform during take-off and
      landing movements. In the regular players, the BMDs of the left leg were
      significantly higher than those of the right leg at the femoral necks, greater
      trochanters, and Ward's triangles (p < 0.01 to approximately 0.005). The side-to
      side differences were 4.7 to approximately 9.6%. Regarding the strength
      parameters, the left side was greater than the right side significantly at EXT 60
      degrees/s (p < 0.01), although the overall side-to-side difference was small. In
      the substitutes, the BMDs at the three sites mentioned above were also higher in
      the left leg than the right, but the side-to-side difference was statistically
      significant only at Ward's triangles (93%, p < 0.05). The side-to-side difference
      of strength was not significant. In the controls, there were small left-to-right
      differences of the BMDs, ranging from -1.8 to 0.5%, which was significantly lower
      than in the regular players at each site. The overall average strength
      measurements were larger in the right leg than in the left except at the 120
      degrees/s. The side-to-side difference was statistically significant at EXT 30
      degrees/s and 60 degrees/s (p < 0.05). The peak force was greater in take-off
      than in landing, and the unit time force during take-off was significantly
      greater than that during landing (p < 0.001). In conclusion, regarding the side
      to-side difference of the BMD at proximal femora, our results demonstrate: that
      the left leg for take-off had higher measurements than the right leg for landing
      in both gymnasts' groups, which accounts for the vertical ground reaction force
      during take-off being greater than that during landing; that the difference in
      the regular players group was greater than that in the substitute group, which
      can be explained because the regular players practiced much more than the
      substitutes did; and that there was no difference in the control group.

PMID- 9610756
TI  - Role of vitronectin and its receptors in haemostasis and vascular remodeling.

PMID- 9610757
TI  - Indium-111 DTPA-heparin: radiolabeling, pharmacokinetics, and biodistribution
      following intravenous administration in rat and rabbit.
AB  - Heparin was coupled to DTPA using the bicyclic anhydride and labeled with Indium
      111. This resulted in a radiochemically pure preparation (greater than 95%
      activity in one peak) as determined by high pressure liquid radiochromatography
      and did not affect the anticoagulant properties of heparin. Biodistribution in
      the rat at 1, 20, and 60 minutes after intravenous injection showed rapid blood
      clearance with uptake in the liver followed by bone and kidney when expressed as
      percent injected total dose per organ and liver followed by kidney and spleen
      when expressed as percent injected total dose per gram. Blood elimination in the
      rabbit was 18.5 minutes which decreased to 7.5 minutes when followed by the
      injection of protamine. Radioactivity cleared from the liver and lungs as a
      single exponential with a half-time of 30 minutes, but there was very rapid
      increase of radioactivity in the lungs, peaking at 1-2 minutes, following the
      injection of protamine. Indium-111 DTPA-heparin may be used to study in vivo
      pharmacokinetics and biodistribution of heparin.

PMID- 9610758
TI  - Peptide LSARLAF activates alpha(IIb)beta3 on resting platelets and causes resting
      platelet aggregate formation without platelet shape change.
AB  - Adhesion of resting platelets to fibrinogen was enhanced by a peptide which was
      designed to bind near the presumptive fibrinogen gamma-chain binding site of the
      alpha subunit of the integrin alpha(IIb)beta3. This peptide, but not a scrambled
      control peptide, induced adhesion of resting platelets to fibronectin,
      vitronectin, von Willebrand factor, and monovalent (lacks one functional gamma
      chain) fibrinogen. Resting platelets not treated with the agonist peptide did not
      adhere to these ligands. Agonist peptide induced adhesion of resting platelets to
      Fg was not secretion dependent and was inhibited by the monoclonal antibody 7E3.
      The agonist peptide caused aggregation of resting platelets on resting platelets
      adherent to immobilized Fg without causing platelet shape change. Therefore, the
      agonist peptide may activate alpha(IIb)beta3 by directly inducing a conformation
      change in the receptor on resting platelets.

PMID- 9610759
TI  - Studies of adsorption, activation, and inhibition of factor XII on immobilized
      heparin.
AB  - The aim of the present investigation was to clarify whether immobilized heparin
      does, as previously suggested, prevent triggering of the plasma contact
      activation system. Purified FXII in the absence or presence of antithrombin
      and/or C1 esterase inhibitor as well as plasma was exposed for 1 to 600 seconds
      to a surface modified by end-point immobilization of heparin. With purified
      reagents, a process including surface adsorption and activation of FXII occurred
      within 1 second. In the presence of antithrombin, the resulting surface-bound
      alpha-FXIIa was inhibited within that time. Likewise, the adsorption of native
      FXII from plasma was a rapid process. However, the inhibition of surface-bound
      alpha-FXIIa was slightly slower than with purified components. Nevertheless,
      neither beta-FXIIa nor FXIa were found in the plasma phase. Exposure of a surface
      prepared from heparin molecules, lacking antithrombin binding properties, to
      plasma resulted in surface-bound alpha-FXIIa within 1 second. In the liquid
      phase, beta-FXIIa was detected after 2.5 seconds and, 12 seconds later, FXIIa and
      FXIa in complex with the C1 esterase inhibitor appeared. Addition of heparin to
      plasma prior to surface exposure did not prevent activation of surface-bound
      FXII, nor did it increase the beta-FXIIa inhibition rate and prevent FXI
      activation in plasma, although beta-FXIIa and FXIa-AT complex formation occurred.
      It is concluded that surface-immobilized heparin, unlike heparin in solution,
      effectively inhibits the initial contact activation enzymes by an antithrombin
      mediated mechanism, thereby suppressing the triggering of the intrinsic plasma
      coagulation pathway.

PMID- 9610760
TI  - Physical effects of cholesterol on arterial smooth muscle membranes: evidence of
      immiscible cholesterol domains and alterations in bilayer width during
      atherogenesis.
AB  - Small angle X-ray diffraction was used to examine arterial smooth muscle cell
      (SMC) plasma membranes isolated from control and cholesterol-fed (2%)
      atherosclerotic rabbits. A microsomal membrane enriched with plasma membrane
      obtained from animals fed cholesterol for up to 13 weeks showed a progressive
      elevation in the membrane unesterified (free) cholesterol:phospholipid (C/PL)
      mole ratio. Beyond 9 weeks of cholesterol feeding, X-ray diffraction patterns
      demonstrated a lateral immiscible cholesterol domain at 37 degrees C with a unit
      cell periodicity of 34 A coexisting within the liquid crystalline lipid bilayer.
      On warming, the immiscible cholesterol domain disappeared, and on cooling it
      reappeared, indicating that the immiscible cholesterol domain was fully
      reversible. These effects were reproduced in a model C/PL binary lipid system. In
      rabbits fed cholesterol for less than 9 weeks, lesser increases in membrane C/PL
      mole ratio were observed. X-ray diffraction analysis demonstrated an increase in
      membrane bilayer width that correlated with the C/PL mole ratio. This effect was
      also reproduced in a C/PL binary lipid system. Taken together, these findings
      demonstrate that in vivo, feeding of cholesterol causes cholesterol-phospholipid
      interactions in the membrane bilayer that alter bilayer structure and
      organization. This interaction results in an increase in bilayer width peaking at
      a saturating membrane cholesterol concentration, beyond which lateral phase
      separation occurs resulting in the formation of separate cholesterol bilayer
      domains. These alterations in structure and organization in SMC plasma membranes
      may have significance in phenotypic modulation or aortic SMC during early
      atherogenesis.

PMID- 9610761
TI  - Antilipolytic actions of insulin on basal and hormone-induced lipolysis in rat
      adipocytes.
AB  - The levels of insulin, free fatty acids (FFA), and triglycerides in rat sera
      increase with age. The increase in serum FFA levels accompanied the stimulation
      of basal lipolysis (i.e., lipolysis in the absence of lipolytic agents) in fat
      cells and enlargement of the diameter of the cells. An overnight fast resulted in
      a significant increase in basal lipolysis in fat cells from 6- and 8-week-old
      rats. Although insulin inhibited lipolysis induced by norepinephrine and ACTH at
      a concentration of 10(-10) M, it failed to inhibit basal lipolysis even at a
      concentration of 10(-6) M. Propranolol, another antilipolytic agent like insulin,
      also did not affect basal lipolysis. Insulin did not inhibit the accelerated
      basal lipolysis in enlarged fat cells, fasted fat cells, and sonicated cells.
      These results indicate that insulin inhibits only the lipolysis induced by
      lipolytic agents such as norepinephrine and ACTH but not the basal lipolysis
      found in the absence of lipolytic agents. The possibility that free fatty acids
      produced by enlarged fat cells initiate insulin resistance and diabetes mellitus,
      is discussed.

PMID- 9610762
TI  - Intracellular movement of triacylglycerols in the intestine.
AB  - The intestine can vary its triacylglycerol output rate depending on differing
      physiological conditions. The rate-limiting step in the complex process from
      fatty acid and monoacylglycerol entry to triacylglycerol export is unknown but
      suggested to be the transport of triacylglycerol from the endoplasmic reticulum
      to the Golgi. The present studies were carried out to test this hypothesis. The
      conversion rate of absorbed fatty acid to mucosal triacylglycerol was studied in
      rats infused intraduodenally with trioleoylglycerol, 135 micromol/h, for 6 h
      followed by [3H]oleate. In 30 sec, 79% of the mucosal 3H-labeled fatty acid was
      esterified to [3H]triacylglycerol. The increase in the 3H specific activity of
      triacylglycerol in the endoplasmic reticulum and Golgi was studied in similarly
      prepared rats except that the radio-label was [3H]trioleoylglycerol. The
      endoplasmic reticulum triacylglycerol specific activity was always less than that
      of the Golgi with a steady state not reached until 60 min of
      [3H]trioleoylglycerol infusion. The steady state of [3H]triacylglycerol in the
      lymph was not reached until 70 min of infusion. We conclude that the data are
      consistent with the rate-limiting step in intestinal triacylglycerol export being
      the movement of triacylglycerol from the endoplasmic reticulum to the Golgi as
      the conversion of absorbed fatty acid to triacylglycerol is rapid and the
      movement of triacylglycerol from the Golgi to the lymph is rapid as well.

PMID- 9610763
TI  - Binding and functional effects of transcription factors Sp1 and Sp3 on the
      proximal human lecithin:cholesterol acyltransferase promoter.
AB  - Human lecithin:cholesterol acyltransferase (LCAT) circulates in plasma bound to
      high density lipoproteins (HDL) and modulates the rate by which cholesteryl ester
      is transported to the liver. So far, little is known about the regulation of the
      expression of the LCAT gene. In this study we have defined the cis-elements,
      identified the trans-acting factors and demonstrated their functional effects and
      significance in determining transcriptional activity of the proximal LCAT
      promoter. Using deletion mutants having 5' variable ends (from nucleotides -72 to
      -27), we have identified the presence of two non-consensus GC-rich regions that
      stimulate transcription in HepG2 and HeLa cells. These regions designated sites A
      (-29 to -47) and B (-49 to -65) contain the CCTCC core sequence which in
      electromobility shift analysis is critical for the formation of two DNA-protein
      complexes designated I and II. Site-directed mutagenesis suggests that both sites
      are equally important in promoter activity, and that cooperative interactions
      between both sites are not required for activity. Electromobility shift and
      supershift experiments using oligonucleotides spanning sites A and B identified
      Sp1 and Sp3 as the transcription factors interacting at these sites. To determine
      the significance and functional effects that Sp1 and Sp3 have in regulating LCAT
      promoter activity, we performed transfection experiments in Drosophila SL-2 cells
      as they lack endogenous Sp1 and Sp3. Sp1 but not Sp3 activates the human LCAT
      promoter and when Sp1 is co-transfected along with Sp3, Sp3 functions as a dose
      dependent repressor of Sp1-mediated activation. These findings indicate that Sp1
      is capable of transactivating a reporter gene linked to the LCAT promoter
      containing Sp binding sites and suggests that the levels of Sp3 or the nuclear
      Sp1/Sp3 ratio may play an important role in determining the transcriptional
      activity of the LCAT promoter in vivo.

PMID- 9610764
TI  - Conversion of eicosapentaenoic acid to chain-shortened omega-3 fatty acid
      metabolites by peroxisomal oxidation.
AB  - Human skin fibroblasts can convert arachidonic acid to 14- and 16-carbon
      polyunsaturated fatty acid products by peroxisomal beta-oxidation. The purpose of
      this study was to determine whether similar products are formed from
      eicosapentaenoic acid (EPA) and whether EPA and arachidonic acid compete for
      utilization by this oxidative pathway. Three radiolabeled metabolites with
      shorter retention times than EPA on reverse-phase high-performance liquid
      chromatography accumulated in the medium during incubation of fibroblasts with
      [5,6,8,9,11,12,14,15,17,18-3H] EPA ([3H]EPA). These metabolites, which were not
      formed from [1-14C]EPA and were not detected in the cells, were identified as
      tetradecatrienoic acid (14:3n-3), hexadecatetraenoic acid (16:4n-3), and
      octadecatetraenoic acid (18:4n-3). The most abundant product under all of the
      conditions tested was 16:4n-3. [3H]EPA was converted to 16:4n-3 and 14:3n-3 by
      fibroblasts deficient in mitochondrial long-chain acyl CoA dehydrogenase, but not
      by Zellweger syndrome or acyl CoA oxidase mutants that are deficient in
      peroxisomal beta-oxidation. Competition studies indicated that 16:4n-3 formation
      from 5 microM [3H]EPA was reduced by 60% when 10 microM arachidonic acid was
      added, but the conversion of [3H]arachidonic acid to its chain-shortened products
      was not decreased by the addition of 10 microM EPA. These findings demonstrate
      that as in the case of arachidonic acid, chain-shortened polyunsaturated fatty
      acid products accumulate when EPA undergoes peroxisomal beta-oxidation. While EPA
      does not reduce arachidonic acid utilization by this pathway, it is possible that
      some biological actions of EPA may be mediated by the formation of the
      corresponding EPA products, 16:4n-3 and 14:3n-3.

PMID- 9610765
TI  - Plasma and fibroblasts of Tangier disease patients are disturbed in transferring
      phospholipids onto apolipoprotein A-I.
AB  - Plasmas of patients with Tangier disease (TD) lack lipid-rich alpha-HDL which, in
      normal plasma, constitutes the majority of high density lipoprotein (HDL).
      Residual amounts of apolipoprotein (apo)A-I in TD plasma occur as lipid-poor or
      even lipid-free prebeta-HDL. By contrast to normal plasma, TD plasma does not
      convert prebeta-HDL into alpha-HDL. Moreover, fibroblasts of TD patients were
      found to be defective in secreting cholesterol or phospholipids in the presence
      of lipid-free apoA-I. We have therefore hypothesized that both defective
      conversion of prebeta-HDL into alpha-HDL and defective lipid efflux from TD cells
      onto lipid-free apoA-I result from a disturbance in phospholipid transfer
      occurring in both cellular and extracellular compartments. To test this
      hypothesis we established an assay that measures the activity of plasma, cells,
      and cell culture media to transfer radiolabeled phosphatidylcholine (PC),
      phosphatidylethanolamine (PE), and phosphatidylinositol (PI) from vesicles onto
      apoA-I, apoA-II, albumin, or reconstituted HDL. Plasmas, HDL, and lipoprotein
      depleted plasma of normolipidemic probands as well as cell homogenates and
      culture media of normal fibroblasts were active at 37 degrees C but not at 4
      degrees C in transferring radiolabeled PC, PI, and PE dose- and time-dependently
      onto either lipid-free apoA-I or reconstituted HDL. Transfer of
      glycerophospholipids onto apoA-II was much lower than onto apoA-I; transfer onto
      albumin was close to background. Compared to ten normolipidemic plasmas and four
      apoA-I-deficient plasmas, plasmas of six TD patients were significantly reduced
      by 40-50% in their glycerophospholipid transfer activities. Compared to eight
      normal fibroblast cell lines, homogenates and culture media of four TD fibroblast
      cell lines were reduced by 40-50% and 30-35%, respectively, in their activity to
      transfer PC, PI, or PE onto apoA-I. Our data suggest that in TD the same
      mechanism underlies both defective conversion of prebeta-HDL into alpha-HDL and
      impaired efflux of cellular lipids, namely a defective phospholipid transfer.

PMID- 9610766
TI  - Impact of LDL carotenoid and alpha-tocopherol content on LDL oxidation by
      endothelial cells in culture.
AB  - Carotenoids and alpha-tocopherol are dietary, lipophilic antioxidants that may
      protect plasma lipoproteins from oxidation, a process believed to contribute to
      atherogenesis. Previous work demonstrated that after the Cu(II)-initiated
      oxidation of human low density lipoprotein (LDL) in vitro, carotenoids and alpha
      tocopherol were destroyed before significant lipid peroxidation took place, and
      that alpha-tocopherol was destroyed at a much faster rate than were the
      carotenoids. Additionally, in vitro enrichment of LDL with beta-carotene, but not
      with lutein or lycopene, inhibited LDL oxidation. In the present studies the
      impact of LDL carotenoid and alpha-tocopherol content on LDL oxidation by human
      endothelial cells (EaHy-1) in culture was assessed. LDL isolated from 11
      individual donors was incubated at 0.25 mg protein/mL with EaHy-1 cells in Ham's
      F-10 medium for up to 48 h. Formation of lipid hydroperoxides was assessed by
      chemical analysis and the contents of lutein, beta-cryptoxanthin, lycopene, beta
      carotene and alpha-tocopherol were determined by high performance liquid
      chromatography. The extent of lipid peroxidation correlated with the endogenous
      alpha-tocopherol content of the LDL but not with its content of carotenoids. As
      in the Cu(II)-initiated system, carotenoids and alpha-tocopherol were destroyed
      before significant peroxidation took place, but, in the cell-mediated system,
      alpha-tocopherol and the carotenoids were destroyed at comparable rates. Also,
      like the Cu(II)-initiated oxidation, enrichment of the LDL with beta-carotene
      protected it from oxidation by the endothelial cells. However, enrichment with
      either lutein or lycopene actually enhanced the cell-mediated oxidation of the
      LDL. Thus, the specific content of carotenoids in low density lipoprotein (LDL)
      clearly modulates its susceptibility to oxidation, but individual carotenoids may
      either inhibit or promote LDL oxidation.

PMID- 9610767
TI  - Oxidized type IV hypertriglyceridemic VLDL-remnants cause greater macrophage
      cholesteryl ester accumulation than oxidized LDL.
AB  - We have previously shown that very low density lipoproteins (VLDL, Sf 60-400)
      from subjects with type IV hyperlipoproteinemia (HTG-VLDL) will induce
      appreciable cholesteryl ester accumulation in cultured macrophages (J774A.1). The
      present study examined whether copper-mediated oxidative modification of HTG-VLDL
      and their remnants would further enhance cholesteryl ester accumulation in
      J774A.1 cells. Incubation with oxidized VLDL-remnants caused the greatest
      increase in cellular cholesteryl ester concentrations (54-fold) relative to
      control cells (P = 0.001). HTG-VLDL and VLDL-remnants each induced similar
      increases in cholesteryl ester levels (32.3- and 35.8-fold, respectively; both P
      = 0.001), whereas incubation with oxidized HTG-VLDL brought about only a 20.6
      fold increase in cholesteryl ester concentrations (P = 0.014). The increase in
      cellular cholesteryl ester concentrations induced by oxidized VLDL-remnants was
      significantly higher (P < or = 0.04) than that induced by all other lipoproteins
      tested including low density lipoprotein (LDL) and oxidized LDL which caused a
      6.7- and a 35.1-fold increase (P < or = 0.0002 for both), respectively. Unlike
      HTG-VLDL and to a lesser extent VLDL-remnants, uptake of oxidized VLDL and
      oxidized VLDL-remnants did not require catalytically active, cell secreted
      lipoprotein lipase. Co-incubation with polyinosine, which blocks binding to the
      type I scavenger receptor, completely inhibited the cholesteryl ester
      accumulation induced by oxidized HTG-VLDL, oxidized VLDL-remnants and oxidized
      LDL (P < or = 0.02). We conclude that oxidation of VLDL-remnants significantly
      enhances macrophage cholesteryl ester accumulation compared to either HTG-VLDL,
      VLDL-remnants, or oxidized LDL. Uptake of oxidized VLDL and oxidized VLDL
      remnants does not require catalytically active lipoprotein lipase, and involves a
      receptor that can be competed for by polyinosine.

PMID- 9610768
TI  - A 3-basepair deletion in repeat 1 of the LDL receptor promoter reduces
      transcriptional activity in a South African Pedi.
AB  - We have examined a naturally occurring mutation in the promoter region of the low
      density lipoprotein receptor (LDLR) gene of a South African Black patient with a
      clinical diagnosis of familial hypercholesterolemia (FH). The mutation
      constitutes a 3-bp deletion at nucleotide position -92 (FH Pedi-2) in the distal
      Sp1 binding site in repeat 1 of the LDLR promoter. The patient carries a second
      mutant LDLR allele containing a 1-bp deletion in exon 2 (FH Pedi-1) that gives
      rise to a frameshift mutation. Consistent with low receptor activity previously
      observed in cultured fibroblasts from the patient (5-15%), the rate of LDL
      receptor synthesis was markedly reduced to less than 20% of normal. DNase I
      footprint analysis indicated that the -92 mutation abolished binding of Sp1 to
      repeat 1 in the LDLR promoter. Transcription studies in transfected cells using
      normal and mutant promoter fragments linked to a luciferase reporter gene
      demonstrated that the promoter fragment containing the -92 mutation had
      approximately 10% of normal promoter activity. These findings indicate that the
      distal Sp1 binding site is essential for maximal activity of the normal intact
      LDLR promoter.

PMID- 9610769
TI  - Stabilization and cytoskeletal-association of LDL receptor mRNA are mediated by
      distinct domains in its 3' untranslated region.
AB  - The mRNA encoding the human low density lipoprotein (LDL) receptor is transiently
      stabilized after phorbol ester treatment of HepG2 cells and has been shown to
      associate with components of the cytoskeleton in this cell line (G. M. Wilson, E.
      A. Roberts, and R. G. Deeley, J. Lipid Res. 1997. 38: 437-446). Using an episomal
      expression system, fragments of the 3' untranslated region (3'UTR) of LDL
      receptor mRNA were transcribed in fusion with the coding region of beta-globin
      mRNA in HepG2 cells. Analyses of the decay kinetics of these beta-globin-LDL
      receptor fusion mRNA deletion mutants showed that sequences in the proximal 3'UTR
      of LDL receptor mRNA including several AU-rich elements (AREs) were sufficient to
      confer short constitutive mRNA half-life in the heterologous system.
      Stabilization of LDL receptor mRNA in the presence of PMA required sequences in
      the distal 3'UTR, at or near three Alu-like repetitive elements. Furthermore, the
      3'UTR of LDL receptor mRNA conferred cytoskeletal association on the otherwise
      unassociated beta-globin mRNA, by a mechanism involving at least two distinct RNA
      elements. Comparisons of decay kinetics and subcellular localization of
      endogenous LDL receptor mRNA and beta-globin-LDL receptor mRNA fusions in HepG2
      cells have demonstrated that several cis-acting elements in the receptor 3'UTR
      contribute to post-transcriptional regulation of receptor expression, and provide
      further support for involvement of the cytoskeleton in the regulation of LDL
      receptor mRNA turnover.

PMID- 9610770
TI  - Monoacylglycerol binding to human serum albumin: evidence that monooleoylglycerol
      binds at the dansylsarcosine site.
AB  - The binding of monoacylglycerides of long-chain fatty acids to human serum
      albumin has been examined using monooleoylglycerol as the ligand. Binding was
      investigated using changes in tryptophan fluorescence and also the displacement
      of a variety of well-studied fluorescent ligands from human serum albumin (HSA).
      Monooleoylglycerol caused a decrease in fluorescence from tryptophan-214 when
      measured at 350 nm while oleic acid had no effect on fluorescence at this
      wavelength and did not compete with monooleoylglycerol. In contrast, oleic acid
      caused an increase in fluorescence at 330 nm whereas monooleoylglycerol did not
      affect fluorescence intensity at this wavelength. These results suggest that
      these two ligands do not bind to the same site on HSA. From competition studies
      using dansylglycine, dansylsarcosine, 11-(dansylamino)-undecanoic acid and 1
      anilino-8-naphthalenesulfonic acid it was proposed that monooleoylglycerol binds
      at the dansylsarcosine site (site II) of HSA. Monooleoylglycerol was a
      competitive inhibitor of dansylsarcosine binding with a Kd of about 2.5 microM
      whereas oleic acid was not competitive with dansylsarcosine binding.

PMID- 9610771
TI  - Stereochemical structures of synthesized and natural plasmalogalactosylceramides
      from equine brain.
AB  - Modified galactosylceramide with a long-chain cyclic acetal at the sugar moiety,
      plasmalogalactosylceramide, was isolated from equine brain. To identify the
      isomeric stereostructure of the natural product, the plasmalo derivative was
      chemically synthesized from galactosylceramide through acetalization. The
      presence of cyclic acetal linkage, the linked position and length of the acetal
      chain of the synthesized and natural products were determined by proton nuclear
      magnetic resonance spectroscopy and fast-atom bombardment-mass spectrometry, as
      well as gas chromatography-mass spectrometry and gas-liquid chromatography. The
      orientation of the acetal chain linked to galactoside was characterized by
      connectivity between the cyclic acetal proton and ring proton(s) on the sugar
      moiety using the homonuclear Overhauser effect. This revealed that, of the two
      positional isomers of the acetal linkage with 4,6-O-acetal and 3,4-O-acetal
      derivatives obtained from the acetalization reaction, the former positional
      isomer, separated into two spots, was identified to 'endo'- and 'exo'-type acetal
      chains. In comparison to the NMR data of the synthesized derivative, equine brain
      acetalized lipid was found to be an 'endo'-type 4,6-O-acetal derivative.

PMID- 9610772
TI  - HMG-CoA reductase is not the site of the primary defect in phytosterolemia.
AB  - Phytosterolemia is an autosomal recessive disorder characterized by the excessive
      absorption, reduced excretion, and consequent high tissue and plasma levels of
      plant sterols, by the presence of tendon xanthomas, and by premature
      atherosclerosis. Low HMG-CoA reductase (HRase) activity and mass have been
      reported in liver and mononuclear leucocytes and low mRNA levels in liver from
      phytosterolemic subjects. These results led to the proposal that the primary
      defect in this condition involves the HRase gene locus. We examined this
      hypothesis in phytosterolemic subjects and heterozygous parents from four
      unrelated families. A variable number tandem repeat (VNTR) polymorphism of the
      HRase gene in the three informative families and a ScrFI restriction fragment
      length polymorphism (RFLP) within intron 2 of the gene in one of these families,
      segregated independently of the disease phenotype. Biological parentage was
      confirmed in the family in whom both polymorphisms failed to segregate with the
      disorder. These results conclusively exclude the HRase gene locus as the site of
      the primary defect in phytosterolemia. The study was extended by examining plasma
      levels of mevalonic acid and lathosterol, both markers of cholesterol
      biosynthesis, in response to cholestyramine, a bile acid sequestrant that is
      known to up-regulate HRase. Oral administration of cholestyramine resulted in a
      substantial (7.7-fold) increase in mevaIonic acid levels in two phytosterolemic
      subjects, compared with a 2.2-fold rise in their obligate heterozygote parents
      and a 2.3-fold increase in three healthy control subjects. The
      lathosterol/cholesterol (L/C) ratio showed a quantitatively similar response.
      Baseline levels of mevalonate and the L/C ratio were low in the phytosterolemic
      patients in conformity with reports of reduced cholesterol biosynthesis and HRase
      activity in this disorder. These functional data provide support for the concept
      that the primary defect in phytosterolemia does not affect a trans gene locus
      responsible for the constitutive expression or regulation of HMG-CoA reductase.

PMID- 9610773
TI  - Sitosterolemia: exclusion of genes involved in reduced cholesterol biosynthesis.
AB  - Sitosterolemia (phytosterolemia) is a rare autosomal recessively inherited
      disorder that is characterized by premature coronary artery disease, xanthomas,
      and increased plasma plant sterols and 5alpha-stanols. Affected individuals show
      an increased absorption of both cholesterol and sitosterol from the diet,
      decreased bile clearance of these sterols and their metabolites resulting in
      markedly expanded whole body cholesterol and sitosterol pools. Biochemical
      studies have shown that the regulation of the cholesterol biosynthetic pathway
      may be abnormal in this condition. In particular, the activities and mRNA for the
      biosynthetic enzymes, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase
      and HMG-CoA synthase are low in liver biopsy specimens isolated from affected
      individuals, suggesting replete intracellular cholesterol pools. However, the
      membrane expression of hepatocyte low density lipoprotein receptors was
      increased, suggesting discordant regulation. Segregation analyses in three
      families for the genes for HMG-CoA reductase, HMG-CoA synthase, and LDL-receptor
      excluded these as sites of mutation. In view of the previously described
      discordant regulation of the above genes in sitosterolemia, the two major
      regulatory genes for this pathway, sterol regulatory element binding proteins
      (SREBP-1 and -2), were also examined. These genes did not segregate with the
      disease and were thus excluded. Two other genes involved in cholesterol
      absorption and chylomicron secretion, namely acyl coenzyme A:cholesterol
      acyltransferase (ACAT) and microsomal triglyceride transfer protein (MTP) were
      also examined for segregation and similarly excluded. Although the gene defect in
      sitosterolemia therefore remains to be elucidated, important candidate genes have
      been excluded.

PMID- 9610775
TI  - Relationship of HDL and coronary heart disease to a common amino acid
      polymorphism in the cholesteryl ester transfer protein in men with and without
      hypertriglyceridemia.
AB  - Plasma triglyceride (TG) levels are inversely related to HDL-cholesterol levels
      and subjects with high TG and low HDL cholesterol have increased coronary heart
      disease (CHD) risk. Plasma cholesteryl ester transfer protein (CETP) transfers
      cholesteryl esters from HDL to TG-rich lipoproteins. In this study we determined
      the relationship between a common CETP amino acid polymorphism (I405V) and CETP
      and HDL levels and CHD prevalence in 576 men of Japanese ancestry in the Honolulu
      Heart Program cohort. This conservative substitution was associated with altered
      plasma CETP concentration (1.95 +/- 0.54, 1.91 +/- 0.57, and 1.77 +/- 0.57
      microg/ml for the II, IV and VV genotypes, respectively). The distribution of
      plasma CETP concentrations among the VV, but not II, men appeared bimodal (P <
      0.01), suggesting the presence of a functionally significant CETP gene
      mutation(s) in a subset of V alleles. HDL-C levels were higher in VV than IV for
      II men (55.4 +/- 17.4, 51.3 +/- 16.6, 51.1 +/- 17.0 mg/dl, P < 0.04). However,
      the increase in HDL was only significant in VV men with plasma TG > 165 mg/dl.
      Although CHD prevalence was not significantly different among the three genotypes
      in this population, in the subpopulation with high plasma TG, CHD prevalence
      appeared higher among VV than IV or II subjects (38% vs. 27% vs. 18%, P < 0.05
      for an interaction of genotype and plasma TG levels). In fresh plasma from a
      separate group of normolipidemic subjects, the V/I polymorphism was not
      associated with any change in plasma CETP specific activity. The data suggest
      that a widespread and common CETP gene mutation(s) in linkage disequilibrium with
      405V causes low CETP. Among hypertriglyceridemic men this is associated with
      higher HDL and possibly with increased CHD.

PMID- 9610774
TI  - Structural requirements for inhibition of cytokine-induced endothelial activation
      by unsaturated fatty acids.
AB  - Dietary long-chain fatty acids (FA) may influence pathological processes
      involving endothelial activation, including inflammation and atherosclerosis. We
      have previously shown that the n-3 FA docosahexaenoate (DHA) inhibits endothelial
      activation in the range of nutritionally achievable plasma concentrations. The
      present study assessed structural determinants for this effect. Saturated,
      monounsaturated, and n-6 and n-3 polyunsaturated FA were incubated with cultured
      endothelial cells for 24-72 h alone, and then in the presence of interleukin-1,
      tumor necrosis factor, or bacterial lipopolysaccharide for an additional 24 h
      before assessing the expression of the vascular cell adhesion molecule-1 (VCAM-1)
      or other products of endothelial activation. No FA tested per se elicited
      endothelial activation. While saturated FA did not inhibit cytokine-induced
      expression of adhesion molecules, a progressively increasing inhibitory activity
      was observed, for the same chain length, with an increase in double bonds.
      Comparison of FA with the same length and number of unsaturation and only
      differing for the double bond position or for the cis/trans configuration
      indicated no difference in inhibitory potency, indicating no effect of the double
      bond position or configuration. As judged by Northern analysis, these latter FA
      also inhibited VCAM-1 messenger RNA steady state levels to the same extent,
      indicating a pre-translational site of action attributable to the single double
      bond. Thus the double bond is the minimum necessary and sufficient requirement
      for FA inhibition of endothelial activation. These properties are likely relevant
      to the anti-atherogenic and anti-inflammatory properties ascribed to n-3 FA,
      which are able to accommodate the highest number of double bonds in a fatty acid
      of given chain length.

PMID- 9610776
TI  - Effect of probucol on LDL oxidation and atherosclerosis in LDL receptor-deficient
      mice.
AB  - Probucol is a powerful inhibitor of atherosclerosis in a number of animal models.
      However, it is unknown whether this is due to the strong antioxidant protection
      of low density lipoprotein (LDL), to antioxidant effects in the artery wall, or
      to cellular effects not shared by other antioxidants. To investigate whether
      murine models are suitable to study the antiatherogenic mechanisms of probucol,
      three experiments following different protocols were carried out in 135 male and
      female LDL receptor-deficient (LDLR-/-) mice. Treatment groups received a high
      (0.5%) or low (0.025%) dose of probucol, or low-dose probucol plus a high dose
      (0.1%) of vitamin E for periods ranging from 6 to 26 weeks. In all experiments,
      probucol strongly protected LDL against ex vivo oxidation (lag times exceeding
      1400 min in 0.5% probucol-treated mice). Treatment with 0.5% probucol
      significantly lowered both HDL-cholesterol and plasma apolipoprotein (apo)A-I
      concentrations. In all three experiments, treatment with 0.5% probucol
      consistently increased the size of lesions in the aortic origin, from 1.3-fold
      (n.s.) to 2.9-fold (P < 0.05) in female mice and from 3.6- to 3.7-fold in males
      (P < 0.001). Even treatment with 0.025% probucol increased atherosclerosis 1.6
      fold in male mice (P < 0.01). Addition of the high dose of vitamin E did not
      attenuate the pro-atherogenic effect of 0.025% probucol. In conclusion, probucol
      not only failed to decrease but actively increased atherogenesis in LDLR-/- mice
      in a dose-dependent manner, even though it provided a very strong antioxidant
      protection of LDL. This suggests that the reduction of atherosclerosis observed
      in other animal models is due to intracellular effects of probucol not found in
      mice, to differences in the metabolism of probucol, and/or to an overriding
      atherogenic effect of the decrease in HDL in murine models.

PMID- 9610777
TI  - Therapy for X-adrenoleukodystrophy: normalization of very long chain fatty acids
      and inhibition of induction of cytokines by cAMP.
AB  - X-adrenoleukodystrophy (X-ALD) is an inherited fatty acid metabolic disorder with
      secondary manifestation of neuroinflammatory disease process. We report that
      compounds (forskolin, 8-bromo cAMP, and rolipram) that increase cAMP and activate
      protein kinase A (PKA) were found to stimulate the peroxisomal beta-oxidation of
      lignoceric acid (C24:0) whereas compounds (H-89 and myristoylated PKI) that
      decrease cAMP and PKA activity inhibited the peroxisomal beta-oxidation of
      lignoceric acid in cultured skin fibroblasts from X-ALD patients. Consistent with
      the stimulation of beta-oxidation of lignoceric acid, activators of PKA
      normalized the level of very long chain fatty acids (VLCFA) in X-ALD cultured
      skin fibroblasts. This normalization of VLCFA in X-ALD cells with forskolin, 8-Br
      cAMP or with rolipram, an inhibitor of cAMP phosphodiesterase, was realized
      independent of expression of mRNA or protein of the ALD gene, suggesting that
      cAMP derivatives can correct the metabolic defect in X-ALD fibroblasts without
      involving the candidate gene for the disease. Because astrocytes and microglia in
      demyelinating lesions of X-ALD brain express proinflammatory cytokines such as
      tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), we
      examined the effect of cAMP derivatives or rolipram on lipopolysaccharide
      stimulated rat primary astrocytes and microglia and found that cAMP derivatives
      and rolipram inhibited the induction of TNF-alpha and IL-1beta in both astrocytes
      and microglia. The ability of cAMP derivatives and rolipram to block the
      induction of TNF-alpha and IL-1beta in astrocytes and microglia and to normalize
      the fatty acid pathogen in skin fibroblasts of x-adrenoleukodystrophy (X-ALD)
      clearly identify cAMP analogs or rolipram as candidates for potential therapy for
      X-ALD patients.

PMID- 9610778
TI  - Simple detection of a point mutation in LDL receptor gene causing familial
      hypercholesterolemia in southern Italy by allele-specific polymerase chain
      reaction.
AB  - Polymerase chain reaction (PCR) amplification of specific alleles allowed the
      rapid detection of a point mutation (missense Gly528 --> Asp) in exon 11 of the
      low density lipoprotein receptor gene which was otherwise not detectable by exon
      amplification and enzymatic digestion as it does not modify the normal
      restriction pattern. The mutant allele, designated as FH-Palermo-1 from the
      origin of the first carrier family identified, gave a specific PCR product of 109
      bp clearly distinct from the product of 168 bp obtained from other alleles with a
      nonspecific couple of primers. This method allowed us to distinguish one positive
      sample mixed with up to 11 parts of normal DNA. Furthermore, the specific
      amplification product was characterized by a Bsm I restriction site not present
      in nonspecific products.

PMID- 9610779
TI  - Measurement of plasma glycerol specific activity by high performance liquid
      chromatography to determine glycerol flux.
AB  - Previous methods for measuring plasma glycerol specific activity (SA) are
      suboptimal, making the determination of glycerol kinetics in vivo with
      radiotracers difficult. A new high performance liquid chromatography (HPLC)
      method is described that permits the accurate and specific measurement of
      glycerol SA. The method involves isolation of glycerol from plasma and the
      formation of a tribenzoyl derivative. Glycerol rate of appearance was measured in
      five human volunteers using both [2-3H]glycerol and [2H5] glycerol. There was
      close agreement between the glycerol appearance rates measured using the two
      approaches (1.66 +/- 0.14 vs. 1.70 +/- 0.10 micromol x kg(-1) x min(-1),
      respectively, P = NS). This HPLC method offers improved specificity over existing
      methods of measuring glycerol turnover using radiotracers.

PMID- 9610780
TI  - Validation of deuterium incorporation against sterol balance for measurement of
      human cholesterol biosynthesis.
AB  - To examine the validity of the deuterium (D) incorporation technique for
      measurement of human cholesterol synthesis rates, D uptake from D2O into
      cholesterol was compared to sterol balance in 13 subjects each under three
      controlled diet settings. Subjects (age 62 +/- 3.6 yr, body weight 74 +/- 4.0 kg,
      BMI 27 +/- 1.4) consumed weight maintenance diets enriched in either corn oil,
      beef tallow, or stick corn oil margarine over a 5-week period. During the final
      week of the study period, subjects were given 1.2 g/D2O per kg body water. D
      enrichment was measured in plasma water and total cholesterol over 24 h. Also,
      during the final week, dietary intake and fecal elimination rates of cholesterol
      were assessed over one 6-day period to calculate sterol balance. There was no
      significant difference (t = 0.858, P = 0.397) between D incorporation into
      cholesterol (1,183 +/- 92 mg/day) and sterol balance (1,316 +/- 125 mg/day).
      Among diets, net cholesterol biosynthesis measured by D incorporation agreed (r =
      0.745, P = 0.0001) with values derived from sterol balance. The degree of
      association between methods was not influenced by the wide range of fatty acid
      composition of the diet fat. These data demonstrate the utility of the simple,
      non-restrictive deuterium incorporation method as a reliable means of determining
      cholesterol biosynthesis in free-living humans.

PMID- 9610781
TI  - Synthesis of an unsaturated fatty acid analogue (18-(4'-azido-2'
      hydroxybenzoylamino)-oleic acid) and its interaction with
      lysophosphatidylcholine: acyl-CoA-O-acyltransferase.
AB  - Acylation/deacylation reactions represent a basic requirement of triglyceride as
      well as phospholipid metabolism, and maintenance of membrane lipid composition.
      In order to examine enzymes participating in these pathways, we synthesized 18
      (4'-azido-2'-hydroxybenzoylamino)-oleic acid, an iodinable photoaffinity analogue
      of oleic acid as a new tool for analyzing enzymes, especially those binding
      unsaturated fatty acids or acyl-CoAs. For the synthesis of omega-amino-oleic
      acid, coupling two bifunctional Cg-components was used. The described synthesis
      scheme is also suited for the specific generation of other fatty acid analogues
      with distinct positions of the double bond. The functionality of 18-(4'-azido-2'
      hydroxybenzoylamino)-oleic acid was investigated with the enzyme
      lysophosphatidylcholine:acyl-CoA-O-acyltransferase (LAT) [EC 2.3.1.23], an enzyme
      that shows high specificity towards (poly)unsaturated fatty acyl-CoAs. It could
      be shown that the photolabel, esterified with coenzyme A, acts in the dark as a
      reversible inhibitor of the enzyme activity, but photolysis of the label results
      in irreversible inactivation of LAT. This inactivation could be prevented by
      addition of the native substrate arachidonyl-CoA during photolysis. Several
      proteins could be specifically visualized using the iodinated analogue. The data
      indicate that this new photoaffinity label may have application to identify and
      characterize lipid biosynthetic enzymes using unsaturated fatty acids as well as
      acyl-CoA binding proteins and the active site of these proteins.

PMID- 9610782
TI  - Body mass index and hepatic lipase gene (LIPC) polymorphism jointly influence
      postheparin plasma hepatic lipase activity.
AB  - The -514 polymorphism in the hepatic lipase gene (LIPC) is associated with
      decreased hepatic lipase activity. In the present study, the interaction between
      body mass index (BMI), the -514 polymorphism, and hepatic lipase activity was
      examined in 118 white men and in 51 African American men. BMI was significantly
      positively correlated with hepatic lipase activity in both populations. BMI was
      similar in men with genetic differences in hepatic lipase activity, indicating
      that high hepatic lipase activity did not cause increased BMI. The data therefore
      suggest that high BMI leads to increased hepatic lipase activity. The actions of
      BMI and the -514 polymorphism on hepatic lipase activity appear to be additive
      and independent, rather than synergistic. This finding indicates that hepatic
      lipase activity is a multifactorial trait, determined in part by polymorphism
      within the LIPC gene as well as by factors that influence BMI.

PMID- 9610783
TI  - Risk factors for breast cancer in women with a breast cancer family history.
AB  - Family history (FH) is an important indicator of a woman's future risk of
      developing breast cancer. Using data collected in a large population-based case
      control study (6705 cases and 9341 controls), we examined the associations of
      breast cancer with known risk factors in women reporting a first-degree FH
      (mother or sister), with an emphasis on lifestyle determinants that may be
      altered to reduce risk. First-degree FH was reported by 18.4% (n = 1234) of cases
      and 11.3% (n = 1058) of controls; the overall relative risk (RR) for breast
      cancer associated with a positive history was 1.70 [95% confidence interval (CI),
      1.55-1.87] and 2.34 (95% CI, 1.80-3.02) for breast cancer at age 45 years or
      younger. Among women with a FH, statistically significant inverse associations
      were observed for increasing parity (RR per birth = 0.90; P < 0.0001), intake of
      carotene-rich foods (RR for >2000 IU/day = 0.73; P = 0.02), and strenuous
      activity as a young adult (RR per episode/week = 0.93; P = 0.02). Recent alcohol
      consumption increased risk (RR per 13 g/week = 1.21; P = 0.02), as did weight
      gain during adult life in postmenopausal women (RR per 5 kg = 1.08; P = 0.001).
      Breast-feeding for any duration was associated with a lower RR in parous,
      premenopausal women (RR = 0.59; P = 0.04). Associations for most risk factors
      with breast cancer were similar among women with and without a FH of breast
      cancer; however, a stronger inverse association was observed for parity in women
      with a positive history (P for interaction = 0.04). Based on these data, women
      with a FH may reduce their excess risk of breast cancer through adjustments in
      lifestyle and reproductive choices. The risk associated with FH of breast cancer
      seems to be largely independent of other known risk factors.

PMID- 9610784
TI  - Breastfeeding experience and breast cancer risk among postmenopausal women.
AB  - Results of studies of breastfeeding and postmenopausal breast cancer risk have
      been inconsistent, with many investigators concluding that breastfeeding does not
      influence risk. We examined whether breastfeeding reduces postmenopausal breast
      cancer risk as well as the details of this relationship, including possible
      modification in risk by the age that a woman first breastfed a child and the
      number of children she breastfed. This population-based case-control study
      compared 974 women who were residents of Los Angeles County and newly diagnosed
      with breast cancer to 973 women with no history of breast cancer who were matched
      to patients by age (within 3 years) and neighborhood of residence. Subjects were
      parous and postmenopausal. Breast cancer patients were ages 55-64 years at
      diagnosis. Women who breastfed at least 16 months experienced a reduced odds of
      breast cancer relative to women who never breastfed (odds ratio, 0.73; 95%
      confidence interval, 0.52-1.01). Risk decreased as the number of children
      breastfed increased, but the association was attenuated after accounting for
      lifetime duration of breastfeeding. Breast cancer risk was 30% lower among women
      ages 20-24 years at first breastfeeding than women who had never breastfed (odds
      ratio, 0.69; 95% confidence interval, 0.54-0.88), independent of the effect of
      age at first birth. This study provides some evidence that the protective effect
      of breastfeeding persists into the postmenopausal years. The potential for
      nondifferential error in recall of breastfeeding habits among postmenopausal
      patients and controls may explain the inconsistent results observed across
      studies and underscores the need for careful assessment of this relationship.

PMID- 9610785
TI  - Cigarette smoking, N-acetyltransferases 1 and 2, and breast cancer risk.
AB  - To examine the effects of smoking and N-acetylation genetics on breast cancer
      risk, we analyzed data from an ongoing, population-based, case-control study of
      invasive breast cancer in North Carolina. The study population consisted of 498
      cases and 473 controls, with approximately equal numbers of African-American and
      white women, and women under the age of 50 and age 50 years or older. Among
      premenopausal women, there was no association between current smoking [odds ratio
      (OR), 0.9; 95% confidence interval (CI), 0.5-1.5] or past smoking (OR, 1.0; 95%
      CI, 0.6-1.6) and breast cancer risk. Among postmenopausal women, there was also
      no association with current smoking (OR, 1.2; 95% CI, 0.7-2.0); however, a small
      increase in risk was observed for past smoking (OR, 1.5; 95% CI, 1.0-2.4). For
      postmenopausal women who smoked in the past, ORs and 95% CIs were 3.4 (1.4-8.1)
      for smoking within the past 3 years, 3.0 (1.3-6.7) for smoking 4-9 years ago, and
      0.6 (0.3-1.4) for smoking 10-19 years ago. Neither N-acetyltransferase 1 (NAT1)
      nor N-acetyltransferase 2 (NAT2) genotype alone was associated with increased
      breast cancer risk. There was little evidence for modification of smoking effects
      according to genotype, except among postmenopausal women. Among postmenopausal
      women, ORs for smoking within the past 3 years were greater for women with the
      NAT1*10 genotype (OR, 9.0; 95% CI, 1.9-41.8) than NAT1-non*10 (OR, 2.5; 95% CI,
      0.9-7.2) and greater for NAT2-rapid genotype (OR, 7.4; 95% CI, 1.6-32.6) than
      NAT2-slow (OR, 2.8; 95% CI, 0.4-8.0). Future studies of NAT genotypes and breast
      cancer should investigate the effects of environmental tobacco smoke, diet, and
      other exposures.

PMID- 9610786
TI  - The androgen receptor gene GGN microsatellite and prostate cancer risk.
AB  - The androgen receptor (AR) gene contains a polymorphic GGN microsatellite in exon
      1, which encodes polyglycine in the amino terminus of the AR. Previous work has
      shown that a polymorphic region of CAG repeats also in exon 1 is inversely
      related to the ability of the AR to transactivate other genes and to prostate
      cancer risk. We investigated whether AR gene GGN repeat length is related to
      prostate cancer in a nested study of 582 cases and 794 controls matched on age
      and smoking status in the Physicians' Health Study. DNA was prepared from
      archived blood. Using PCR, the region surrounding the GGN repeat was amplified.
      Fluorescence-labeled primers were used such that the fragment produced could be
      sized using polyacrylamide gels and Genescan software. We estimated odds ratios
      and 95% confidence intervals from logistic models controlling for the matching
      variables for the relation between GGN repeat length and total prostate cancer
      and by stage/grade and by age at diagnosis. Among controls, the most frequent GGN
      repeat lengths were 23 (53.5%) and 24 (34.0%), with a range of 10-29. There was
      no statistically significant difference in the mean GGN repeat length between
      cases (23.13) and controls (23.05). However, cases had a narrower spread of
      repeats lengths (parametric test, P = 0.03; nonparametric test, P = 0.07) than
      controls, with fewer extreme lengths in either direction. The risk of total
      prostate cancer was slightly increased for a GGN repeat length of 23 compared to
      all others (odds ratio, 1.20; 95% confidence interval 0.97-1.49); risk did not
      vary by tumor stage/grade. For every one repeat deviation in either direction
      from 23, the risk of prostate cancer decreased by 8% (P = 0.04). Although the AR
      gene GGN repeat probably plays only a modest role in prostate cancer, the
      observed relation of this repeat with prostate cancer risk supports the
      evaluation of the effect of GGN repeat length on AR transactivation.

PMID- 9610787
TI  - Vitamin D receptor polymorphisms, circulating vitamin D metabolites, and risk of
      prostate cancer in United States physicians.
AB  - Prostatic cells express vitamin D receptor (VDR), which mediates the functions of
      1,25-dihydroxyvitamin D. Two recent case-control studies suggested strong inverse
      associations between two VDR polymorphisms, TaqI and poly(A), and risk of
      prostate cancer. These two and a third polymorphism, BsmI, are closely linked. In
      a case-control study nested in the Physicians' Health Study, a randomized double
      blind trial of aspirin and beta-carotene among 22,071 United States male
      physicians, we examined the associations between BsmI and TaqI and prostate
      cancer risk and whether the associations varied according to age and vitamin D
      metabolite levels among 372 incident cases and 591 controls. Among controls, the
      BB genotype was significantly associated with higher 1,25-dihydroxyvitamin D
      (median = 36.2 pg/ml for the BB versus 33.9 pg/ml for the bb genotype; P = 0.02),
      suggesting an association of the VDR polymorphisms with VDR function. Overall, we
      observed no significant associations of these VDR polymorphisms with prostate
      cancer risk: relative risk (RR) = 0.86 [95% confidence interval (CI) = 0.57-1.29]
      for the BB genotype and RR = 0.92 (95% CI = 0.69-1.22) for the Bb genotype,
      compared with the bb genotype (results were similar for the TaqI polymorphism).
      Stratification by age (< or = 61 and > 61 years) and tumor aggressiveness showed
      no significant associations. However, in an analysis restricted to men with
      plasma 25-hydroxyvitamin D below the median, we observed a 57% reduction (RR =
      0.43, 95% CI = 0.19-0.98) in risk for those with the BB versus the bb genotype;
      the risk reduction was particularly marked among older men (RR = 0.18, 95% CI =
      0.05-0.68). We did not observe this inverse association among men with 25
      hydroxyvitamin D levels above the median, nor did we observe it among younger
      men.

PMID- 9610788
TI  - Human prostate cells synthesize 1,25-dihydroxyvitamin D3 from 25-hydroxyvitamin
      D3.
AB  - Epidemiological and laboratory data support a role for vitamin D in the growth
      and differentiation of human prostatic cells. These findings prompted us to ask
      whether prostatic cells could convert 25-hydroxyvitamin D3 (25-OH-D3), the major
      circulating metabolite of vitamin D3, to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3],
      the hormonally active metabolite, in a manner similar to cultured human
      keratinocytes. Therefore, we investigated three well-characterized human prostate
      cancer cell lines, LNCaP, DU 145, and PC-3; two primary cultures of cells derived
      from noncancerous human prostates (one normal and one benign prostatic
      hyperplasia); and primary cultures of normal human keratinocytes for their
      ability to synthesize 1,25(OH)2D3. Assays were performed in the presence of 25-OH
      D3 as the enzyme substrate and 1,2-dianilinoethane, an antioxidant and free
      radical scavenger, and in the presence and absence of clotrimazole, a cytochrome
      P450 inhibitor. DU 145 and PC-3 cells produced 0.31 +/- 0.06 and 0.07 +/- 0.01
      pmol of 1,25(OH)2D3/mg protein/h, respectively. No measurable 1,25(OH)2D3 was
      detected in LNCaP cells. The normal and benign prostatic hyperplasia primary
      cultures and keratinocyte cultures produced 3.08 +/- 1.56, 1.05 +/- 0.31, and 2.1
      +/- 0.1 pmol of 1,25(OH)2D3/mg protein/h, respectively, using a calf thymus
      receptor binding assay to measure 1,25(OH)2D3 in the presence of 1,2
      dianilinoethane. The identity of the analyte as 1,25(OH)2D3 was supported by high
      performance liquid chromatography using [3H]25-OH-D3 as the enzyme substrate and
      a solvent system that is specific for 1,25(OH)2D3. The production of 1,25(OH)2D3
      in the prostate cancer cell lines and in the primary cultures was completely
      inhibited in the presence of clotrimazole. This report demonstrates that two of
      three human prostate cancer cell lines, as well as primary cultures of
      noncancerous prostatic cells, possess 1alpha-hydroxylase activity and can
      synthesize 1,25(OH)2D3 from 25-OH-D3. Together with recent data indicating that
      1,25(OH)2D3 inhibits the invasiveness of human prostate cancer cells (G. G.
      Schwartz et al., Cancer Epidemiol. Biomark. Prev., 6: 727-732, 1997), these data
      suggest a potential role for 25-OH-D3 in the chemoprevention of invasive prostate
      cancer.

PMID- 9610789
TI  - p53 mutations in cyclophosphamide-associated bladder cancer.
AB  - Cyclophosphamide is a known bladder carcinogen, with cumulative dose directly
      related to increased risk. There is no consensus, however, on which major
      cyclophosphamide metabolite (i.e., acrolein or phosphoramide mustard) drives
      bladder carcinogenesis. We examined 19 cyclophosphamide-related bladder tumors to
      test the hypothesis that they might contain somatic mutations in the p53 tumor
      suppressor gene that could link a specific metabolite to the etiology of these
      cancers. Forty-three % (9 of 19) of the cases had a mutation in p53, with a
      predominance at G:C bp (7 of 9, 77%), a preference for non-CpG sites (6 of 7,
      86%), and frequent G:C-->A:T transitions (5 of 7, 71%). The p53 mutation spectrum
      of these cyclophosphamide-associated bladder cancers differed significantly from
      patterns reported for sporadic (P = 0.020), smoking-related (0.043), and
      schistosomiasis-linked (P = 0.002) tumors but not arylamine-associated neoplasms
      (P = 0.860). Differences between the cyclophosphamide and arylamine-associated
      spectra included an unusual degree of clustering of exon 6 mutations (43% versus
      17%, respectively) and an absence of multiple mutations in the former. Notably
      lacking in our series were G:C-->T:A transversions, the principal mutation
      associated with acrolein. Instead, the mutation spectrum matches the
      phosphoramide mustard adduction sequences determined by a repetitive primer
      extension assay (P = 0.024), indicating that this metabolite might be a key
      mutagen in cyclophosphamide-related bladder cancer.

PMID- 9610790
TI  - Strategies for recruitment to a population-based lung cancer prevention trial:
      the CARET experience with heavy smokers. Beta-Carotene and Retinol Efficacy
      Trial.
AB  - The Beta-Carotene and Retinol Efficacy Trial tested the effect of the combination
      of beta-carotene (30 mg) and retinyl palmitate (25,000 units) daily on the
      incidence of lung cancer in high-risk individuals. In study centers located in
      Seattle, WA; Portland, OR; and Irvine, CA, we recruited current and recent ex
      cigarette smokers, aged 50-69 years. Our primary method of recruitment was by
      mailing study information and eligibility questionnaires to age-selected health
      insurance subscribers. A total of 1,216,549 subscriber households were contacted,
      which resulted in 16,449 enrollments and 12,184 randomizations. Other methods of
      recruitment yielded 1421 enrollments and 1002 randomizations. Seventy-four % of
      those participants who enrolled in the 3-month placebo run-in were randomized.
      The major reasons for nonrandomization once subjects were enrolled were: becoming
      ineligible (13%), concern about or development of side effects attributed to the
      study vitamins (18%), loss of interest or being too busy (23%), and not showing
      up at the appointed time or not willing to come to the study center (23%). Here,
      we discuss the reasons for nonparticipation and for subjects leaving the trial
      prior to randomization and possible modifications of trial design and procedures
      to address these problems. This recruitment approach provided a constant flow of
      potentially eligible participants, screened out many ineligible and uninterested
      persons prior to the scheduling of a study center visit, and ensured
      randomization of committed participants. A major limitation of this study was
      that the pool of minorities that was reached was small.

PMID- 9610791
TI  - Association of Ile462Val (Exon 7) polymorphism of cytochrome P450 IA1 with lung
      cancer in the Asian population: further evidence from a case-control study in
      Okinawa.
AB  - Okinawa, a group of islands that lie between the East China Sea and the Pacific
      Ocean, 2000 km south of the Japanese main islands, has a different profile of
      diseases, ethnicities, and cultures than does the rest of Japan. We examined an
      Ile462Val polymorphism (CYP1A1*2 allele) of cytochrome P450 IA1 in a hospital
      based case-control study of lung cancer patients (247 cases and 185 controls) in
      Okinawa to ascertain the association of this variant with lung cancer. In
      addition, the distribution of this genotype was studied in populations from
      different areas of Japan, including Tokyo (n = 69) and Iwate (northern part of
      Japan; n = 81), as well as in a Chinese group from the Jiangsu province (n = 39)
      and in an Australian Caucasian group (n = 146). Genotype frequency in controls
      was not significantly different from area to area in Japan. In Okinawa, however,
      the genotype encoding Val/Val was associated with a significantly higher risk of
      lung cancer (odds ratio = 3.32, P = 0.013), especially of squamous cell carcinoma
      and small cell carcinoma (odds ratio = 4.85 and 9.35, respectively). The Val
      encoding allele was less frequent in the Chinese population and was rare in
      Australian Caucasians. Thus, this study gives support to the value of the
      cytochrome P450 IA1 Ile462Val polymorphism as a practical high-risk marker of
      lung cancer in populations, especially those in southeast Asia, in which this
      variant is more common.

PMID- 9610792
TI  - Inhaled cellulosic and plastic fibers found in human lung tissue.
AB  - We report the results of studies undertaken to determine whether inhaled plant
      (i.e., cellulosic; e.g., cotton) and plastic (e.g., polyester) fibers are present
      in human lungs and, if so, whether inhaled fibers are also present in human lung
      cancers. Specimens of lung cancer of different histological types and adjacent
      nonneoplastic lung tissue were obtained from patients undergoing a lung resection
      for removal of a tumor. With the protection of a laminar flow hood and safeguards
      to prevent contamination by extraneous fibers, fresh, nonfixed, and nonstained
      samples of lung tissue were compressed between two glass microscope slides.
      Specimens in these dual slide chambers were examined with a microscope configured
      to permit viewing with white light, fluorescent light, polarizing light, and
      phase-contrast illumination. Near-term fetal bovine lungs and nonlung human
      tumors were used as controls. In contrast to the observations of these control
      tissues, morphologically heterogeneous fibers were seen repetitively in freshly
      excised human lung tissue using polarized light. Inhaled fibers were present in
      83% of nonneoplastic lung specimens (n = 67/81) and in 97% of malignant lung
      specimens (n = 32/33). Thus, of the 114 human lung specimens examined, fibers
      were observed in 99 (87%). Examination of histopathology slides of lung tissue
      with polarized light confirmed the presence of inhaled cellulosic and plastic
      fibers. Of 160 surgical histopathology lung tissue slides, 17 were selected for
      critical examination; of these, fibers were identified in 13 slides. The
      inhalation of mineral (e.g., asbestos) fibers has been described by many
      investigators; we believe, however, that this is the first report of inhaled
      nonmineral (e.g., plant and plastic) fibers. These bioresistant and biopersistent
      cellulosic and plastic fibers are candidate agents contributing to the risk of
      lung cancer.

PMID- 9610793
TI  - Tobacco use in relation to renal cell carcinoma.
AB  - The modest effect of cigarette smoking on renal cell carcinoma (RCC) requires a
      study with a large number of subjects to definitively answer the question of
      whether smoking is causally related to RCC. A population-based case-control study
      was conducted in Los Angeles, California that involved 1204 RCC patients and an
      equal number of neighborhood controls who were matched to the index cases by sex,
      date of birth (within 5 years), and race. Detailed information on tobacco use was
      collected through in-person interviews. Cigarette smoking was associated with a
      statistically significant 35% increase in the risk of RCC [odds ratio (OR), 1.35;
      95% confidence interval (CI), 1.14-1.60]. The risk increased with increasing
      number of cigarettes smoked per day (two-sided P < 0.001, linear trend test).
      Former smokers (OR, 1.24; 95% CI, 1.02-1.50) had a lower risk of RCC than current
      smokers (OR, 1.53; 95% CI, 1.23-1.90). Compared with current smokers, those who
      quit smoking 10 or more years ago experienced a statistically significant 30%
      reduction in the risk of RCC. Current smokers who smoked 40 or more
      cigarettes/day experienced a nearly 2-fold increase in the risk of RCC compared
      with lifelong nonsmokers. The association between cigarette smoking and RCC was
      similar in men and women. There were no measurable differences in the risk of RCC
      between filtered and nonfiltered cigarette smokers or between those who inhaled
      cigarette smoke deeply and those who inhaled lightly after adjustment for the
      number of cigarettes smoked per day and current smoking status. After the effect
      of cigarette smoking was accounted for, heavy cigar smokers (14 or more
      cigars/week) exhibited a statistically significant 70% increase in the risk of
      RCC, but no increased risk of RCC was observed for the use of pipes or smokeless
      tobacco. Seventeen percent of RCC (21% in men and 11% in women) in Los Angeles,
      California can be attributed to cigarette smoking.

PMID- 9610794
TI  - Lipid peroxidation-induced etheno-DNA adducts in the liver of patients with the
      genetic metal storage disorders Wilson's disease and primary hemochromatosis.
AB  - To assess DNA damage caused by lipid peroxidation due to copper and iron storage
      disorders in the human liver, the formation of the etheno adducts 1,N6
      ethenodeoxyadenosine (epsilon dA) and 3,N4-ethenodeoxycytine (epsilon dC) was
      measured in liver DNA from normal subjects and from patients with Wilson's
      disease (WD) and primary hemochromatosis. The mean epsilon dA and epsilon dC
      levels per 10(9) parent nucleotides in normal liver were 19.3 +/- 4.9 and 27.5 +/
      10.0, respectively. The mean epsilon dA and epsilon dC levels per 10(9) parent
      nucleotides in WD were 61.03 +/- 7.95 and 91.50 +/- 36.02, and in primary
      hemochromatosis, they were 46.62 +/- 32.83 and 64.32 +/- 11.55, respectively, two
      to three times higher than those in the normal liver. The etheno adduct levels
      were highly correlated with the copper content of the liver in the normal and WD
      samples. This study demonstrates for the first time the formation of promutagenic
      etheno adducts in humans in association with copper and iron storage-induced
      lipid peroxidation. Thus, the etheno adducts are implicated as initiating DNA
      damage in copper/iron-induced carcinogenesis in humans and should also be
      explored as biomarkers in disease progression and prevention trials.

PMID- 9610795
TI  - Detectable levels of serum aflatoxin B1-albumin adducts in the United Kingdom
      population: implications for aflatoxin-B1 exposure in the United Kingdom.
AB  - This study aimed to estimate aflatoxin B1 (AFB1) exposure in the United Kingdom
      population by measuring levels of serum AFB1-albumin (alb), using immunoassay and
      high-performance liquid chromatography (HPLC) with fluorescence detection. A self
      questionnaire on dietary habits from 104 volunteers (47 men and 57 women) in York
      was completed, and blood samples were collected. Serum alb was extracted, and
      AFB1-lysine (lys), the digest product of AFB1-alb, was isolated and measured. A
      sensitive ELISA (detection limit, approximately 1.4 pg of AFB1-lys) was
      developed. A good correlation was found between calibration of ELISA results and
      scintillation counting, for rats dosed with [3H]AFB1 (r = 0.972; P < 0.001). This
      ELISA was subsequently used to analyze human serum alb. For United Kingdom human
      sera, the mean adduct levels were 29.3 +/- 14.8 pg AFB1-lys equivalents (eq) mg
      albumin (males) and 26.9 +/- 14.4 pg AFB1-lys eq/mg alb (females). Confirmation
      of the ELISA data was sought using reversed-phase HPLC with fluorescence
      detection. HPLC chromatograms of digested York serum alb were compared to
      digested serum alb for humans from Qidong County, People's Republic of China, and
      from AFB1-dosed rats. These all gave similar HPLC profiles. Each sample contained
      fluorescent material that coeluted with and just before the AFB1-lys standard.
      Fluorescent fractions were found to be inhibitory in a separate anti-AFB1-lys
      ELISA, indicating that these earlier fluorescent peaks contained AFB1 residues.
      Our results suggest that measurable internal AFB1 exposure may be occurring in
      some United Kingdom individuals, albeit at lower levels than those seen for areas
      with high AFB1 exposure. The source of this exposure may reflect the known
      difficulties in accurately monitoring regulated imported foodstuffs and/or the
      lack of regulations on other potentially contaminated imports. However, no
      positive correlations were found between our AFB1-lys measurements and any
      dietary questionnaire information. Animal studies, as well as human studies, have
      been important in developing exposure and internal adduct relationships in
      humans. Based on this literature, our AFB1-alb data indicate a mean daily
      exposure of 3 microg of AFB1 and a mean internal dose in liver DNA of 5.9
      adducts/10(7) nucleotides. We believe this may be an overestimate of the AFB1
      exposure level in the United Kingdom, and further studies are needed to
      accurately relate external dose and internal AFB1 biomarkers in humans.

PMID- 9610796
TI  - Epstein-Barr virus involvement in gastric cancer: biomarker for lymph node
      metastasis.
AB  - EBV involvement in gastric cancer is characterized by episomal monoclonality,
      high antibody titers, EBV encoded small RNA and EBV nuclear antigen 1 expression
      in all tumor cells, and in the intramucosal stage, by a unique morphology. EBV
      involvement varies by population (approximately 7% of gastric cancers in Japan
      and >15% in Western countries), sex, histological type, and tumor location. The
      present study compares frequency of lymph node metastasis (LNM) between 170 EBV
      positive and 1590 EBV-negative gastric cancer cases in Japan by level of
      invasiveness. Frequency of LNM increased with increasing depth of invasiveness
      but was consistently and significantly greater for EBV-negative cases (P =
      0.0018). In particular, there were no instances of LNM among 75 EBV-positive
      cases as compared with 53 among 562 EBV-negative cases restricted to the mucosa
      and submucosa (odds ratio, 0; 95% confidence limits, 0-0.20). The finding
      suggests that genetic control of metastasis may differ between EBV-related and
      other gastric cancers. Also, the possibility that EBV-positive, noninvasive
      gastric cancers may not require lymph node dissection suggests that routine assay
      of biopsy specimens for EBV involvement could be important in populations, like
      that of Japan, where early gastric cancers are seen frequently.

PMID- 9610798
TI  - A comparison of disease and gene frequencies of inborn errors of metabolism among
      different ethnic groups in the West Midlands, UK.
AB  - OBJECTIVE: To assess birth and gene frequencies of specific autosomal recessively
      inborn errors of metabolism (IEM) within different ethnic groups. DESIGN:
      Retrospective study in a regional centre for investigation and treatment of IEM.
      SUBJECTS: All children born within the West Midlands NHS Region, UK, during the
      decade immediately preceding the 1991 National Census. METHODS: Birth frequencies
      for individual IEM were calculated separately for the main ethnic groups in the
      West Midlands using data from the West Midlands Neonatal Screening Programme, the
      regional register of IEM patients, and population frequencies from the National
      Census. Gene frequencies were calculated using previously documented observations
      on parental consanguinity rates and inbreeding coefficients. RESULTS: The overall
      incidence of recorded IEM was tenfold higher among Pakistanis compared to white
      children (1:318 v 1:3760), whereas only one AfroCaribbean child was identified
      (incidence 1:16 887). Tyrosinaemia type 1, cystinosis, mucopolysaccharidosis type
      1, non-ketotic hyperglycinaemia, and hyperchylomicronaemia all occurred more
      frequently among Pakistanis. An increased gene frequency was only confirmed for
      tyrosinaemia. The incidence of phenylketonuria was similar in Pakistani and white
      children (1:14 452 v 1:12 611), but the gene frequency was significantly lower in
      Pakistanis (1:713 v 1:112). These results illustrate the interplay between gene
      frequency and parental consanguinity in determining disease frequencies in
      different populations, and indicate anticipated disease frequencies in the
      absence of consanguineous marriage. These figures have implications for the
      organisation of services for management of inborn errors, for genetic
      counselling, and for the assessment of gene flow in world populations.

PMID- 9610797
TI  - Hereditary fructose intolerance.
AB  - Hereditary fructose intolerance (HFI, OMIM 22960), caused by catalytic deficiency
      of aldolase B (fructose-1,6-bisphosphate aldolase, EC 4.1.2.13), is a recessively
      inherited condition in which affected homozygotes develop hypoglycaemic and
      severe abdominal symptoms after taking foods containing fructose and cognate
      sugars. Continued ingestion of noxious sugars leads to hepatic and renal injury
      and growth retardation; parenteral administration of fructose or sorbitol may be
      fatal. Direct detection of a few mutations in the human aldolase B gene on
      chromosome 9q facilitates the genetic diagnosis of HFI in many symptomatic
      patients. The severity of the disease phenotype appears to be independent of the
      nature of the aldolase B gene mutations so far identified. It appears that
      hitherto there has been little, if any, selection against mutant aldolase B
      alleles in the population: in the UK, approximately 1.3% of neonates harbour one
      copy of the prevalent A149P disease allele. The ascendance of sugar as a major
      dietary nutrient, especially in western societies, may account for the increasing
      recognition of HFI as a nutritional disease and has shown the prevalence of
      mutant aldolase B genes in the general population. The severity of clinical
      expression correlates well with the immediate nutritional environment, age,
      culture, and eating habits of affected subjects. Here we review the biochemical,
      genetic, and molecular basis of human aldolase B deficiency in HFI, a disorder
      which responds to dietary therapy and in which the principal manifestations of
      disease are thus preventable.

PMID- 9610799
TI  - Prediction of liability to orofacial clefting using genetic and craniofacial data
      from parents.
AB  - BACKGROUND: Cleft lip with or without cleft palate (CL(P)) and isolated cleft
      palate (CP) are separate clinical entities and for both polygenic multifactorial
      aetiology has been proposed. Parents of children with orofacial clefting have
      been shown to have distinctive differences in their facial shape when compared to
      matched controls. OBJECTIVE: To test the hypothesis that genetic and morphometric
      factors predispose to orofacial clefting and that these markers differ for CL(P)
      and CP. Methods-Polymorphisms at the transforming growth factor alpha (TGFalpha)
      locus in 83 parents of children with nonsyndromic orofacial clefts were analysed,
      and their craniofacial morphology was assessed using lateral cephalometry.
      RESULTS: Parents of children with CL(P) and CP showed an increased frequency of
      the TGFalpha/TaqI C2 allele (RR=4.10, p=0.009) relative to the comparison group.
      Also the TGFalpha/BamHI A1 allele was more prevalent in the CP parents.
      MULTIVARIATE STATISTICAL ANALYSIS: Using stepwise logistic regression analysis
      the TGFalpha/TaqI C2 polymorphism provides the best model for liability to
      orofacial clefting. To determine the type of clefting a model involving
      interaction between the parental TGFalpha/BamHI and TGFalpha/RsaI genotypes
      showed the best fit. Using genotype only to predict the clefting defect in the
      children according to parental genotype, 68.3% could be correctly classified. By
      adding information on craniofacial measurements in the parents, 76% of CP and 94%
      of CL(P) parents could be correctly classified. CONCLUSIONS: This study provides
      a model for prediction of liability to orofacial clefting. These findings suggest
      that different molecular aberrations at the TGFalpha locus may modify the risk
      for CP and CL(P).

PMID- 9610800
TI  - Abnormalities of dystrophin, the sarcoglycans, and laminin alpha2 in the muscular
      dystrophies.
AB  - Abnormalities of dystrophin, the sarcoglycans, and laminin alpha2 are responsible
      for a subset of the muscular dystrophies. In this study we aim to characterise
      the nature and frequency of abnormalities of these proteins in an Australian
      population and to formulate an investigative algorithm to aid in approaching the
      diagnosis of the muscular dystrophies. To reduce ascertainment bias, biopsies
      with dystrophic (n=131) and non-dystrophic myopathic (n=71) changes were studied
      with antibodies to dystrophin, alpha, beta, and gamma sarcoglycan, beta
      dystroglycan, and laminin alpha2, and results were correlated with clinical
      phenotype. Abnormalities of dystrophin, the sarcoglycans, or laminin alpha2 were
      present in 61/131 (47%) dystrophic biopsies and in 0/71 myopathic biopsies,
      suggesting that immunocytochemical study of dystrophin, the sarcoglycans, and
      laminin alpha2 may, in general, be restricted to patients with dystrophic
      biopsies. Two patients with mutations identified in gamma sarcoglycan had
      abnormal dystrophin (by immunocytochemistry and immunoblot), showing that
      abnormalities of dystrophin may be a secondary phenomenon. Therefore, biopsies
      should not be excluded from sarcoglycan analysis on the basis of abnormal
      dystrophin alone. The diagnostic yield was highest in those with severe, rapidly
      progressive limb-girdle weakness (92%). Laminin alpha2 deficiency was identified
      in 5/131 (4%) patients; 215 patients presented after infancy, indicating that
      abnormalities of laminin alpha2 are not limited to the congenital muscular
      dystrophy phenotype. Overall patterns of immunocytochemistry and immunoblotting
      provided a guide to mutation analysis and, on the basis of this study, we have
      formulated a diagnostic algorithm to guide the investigation of patients with
      muscular dystrophy.

PMID- 9610801
TI  - Molecular study of the rhodopsin gene in retinitis pigmentosa patients in the
      Basque Country.
AB  - Retinitis pigmentosa (RP) is a degenerative disorder affecting the outer segment
      of the retina and leading to night blindness and progressive visual field loss.
      The rhodopsin gene encodes a photolabile pigment located in the rod outer
      segments constituting around 80-90% of its protein content and is the initiation
      point for the visual cascade upon absorption of a single photon. Seventy-five
      unrelated, isolated RP families in the Basque Country, with at least one affected
      member, were diagnosed at our hospital after ophthalmic examination and
      electroretinogram analysis. The patients received genetic counselling according
      to their individual case based on their clinical diagnosis. The modes of
      inheritance found from pedigree studies were the following: 20% (15/75) were
      classified as autosomal dominant retinitis pigmentosa (ADRP), 17.33% (13/75) were
      autosomal recessive (ARRP), 2.66% (2/75) were unclassified (NC), and 60% (45/75)
      were sporadic cases (SCRP). From these families, 75 unrelated and affected index
      cases together with 22 affected relatives and 42 unaffected relatives were
      screened for mutations in the rhodopsin gene by GC clamped denaturing gradient
      gel electrophoresis. Our results showed that five ADRP, three ARRP, 15 SCRP, and
      one NC families had alterations in this gene. Only three of these alterations,
      that is 4% (3/75) (95% CL 0-8), appeared to be responsible for the disease. This
      represents a lower percentage than the 10% previously reported.

PMID- 9610802
TI  - Linkage analysis in Usher syndrome type I (USH1) families from Spain.
AB  - Usher syndrome (USH) is an autosomal recessive hereditary disorder characterised
      by congenital sensorineural hearing loss and gradual visual impairment secondary
      to retinitis pigmentosa (RP). The disorder is clinically and genetically
      heterogeneous. With regard to Usher type I (USH1), several subtypes have been
      described, the most frequent being USH1B located on chromosome 11q13.5. Of 18
      USH1 families studied by linkage analysis, 12 (67%) showed significant lod score
      values for locus D11S527 (Zmax=14.032, theta=0.000) situated on chromosome 11q.
      Our findings suggest considerable genetic heterogeneity in the Spanish USH1
      population. It is important to note that one of our families linked to the USH1B
      locus shows interesting intrafamilial clinical variability. As regards the
      remaining six USH1 families, the linkage analysis did not provide conclusive
      data, although two of them show slight linkage to markers located on chromosome
      3q (Zmax=1.880, theta=0.000 for D3S1279), the same location that had previously
      been assigned to some USH3 families.

PMID- 9610803
TI  - Genotype-phenotype correlation in L1 associated diseases.
AB  - The neural cell adhesion molecule L1 (L1CAM) plays a key role during embryonic
      development of the nervous system and is involved in memory and learning.
      Mutations in the L1 gene are responsible for four X linked neurological
      conditions: X linked hydrocephalus (HSAS), MASA syndrome, complicated spastic
      paraplegia type 1 (SP-1), and X linked agenesis of the corpus callosum. As the
      clinical picture of these four L1 associated diseases shows considerable overlap
      and is characterised by Corpus callosum hypoplasia, mental Retardation, Adducted
      thumbs, Spastic paraplegia, and Hydrocephalus, these conditions have recently
      been lumped together into the CRASH syndrome. We investigate here whether a
      genotype-phenotype correlation exists in CRASH syndrome since its clinical
      spectrum is highly variable and numerous L1 mutations have been described. We
      found that (1) mutations in the extracellular part of L1 leading to truncation or
      absence of L1 cause a severe phenotype, (2) mutations in the cytoplasmic domain
      of L1 give rise to a milder phenotype than extracellular mutations, and (3)
      extracellular missense mutations affecting amino acids situated on the surface of
      a domain cause a milder phenotype than those affecting amino acids buried in the
      core of the domain.

PMID- 9610804
TI  - Psychosocial adaptation in adolescents and young adults with Marfan syndrome: an
      exploratory study.
AB  - We conducted a pilot study to evaluate the psychological effects and consequences
      of Marfan syndrome in 17 patients between 16 and 35 years of age. Through a semi
      structured interview, we investigated how the patients coped daily with Marfan
      syndrome and evaluated the impact of the disease on specific items such as
      schooling, occupational choices, self-image, and social behaviour. A second part
      of the study consisted of a battery of standardised psychological tests to
      evaluate the patients' anxiety and depression levels and coping styles. The
      following psychological tests were used: State and Trait Anxiety Inventory
      (STAI), Beck Depression Inventory (BDI), and the Utrecht Coping List (UCL). The
      interviews showed that the disease represented a significant burden on the daily
      physical activities of the patients, as well as on their schooling and job
      opportunities. During childhood, most of them were insensitively teased by peers
      because of their typical phenotypic features. This had its consequences on their
      social behaviour in that they are all more introvert. In the female patients, the
      risk associated with child bearing represented a major concern. Most patients
      emphasised the need for accurate information about the illness immediately after
      knowing the diagnosis and all found psychological support helpful. Depression and
      anxiety levels were higher in the female than in the male group, without being
      significantly different from the normal population. Nevertheless, most patients
      have come to terms with their disease and consider themselves happy most of the
      time.

PMID- 9610805
TI  - Recommendations for education and training of genetic nurses and counsellors in
      the United Kingdom.
AB  - Genetic nurses and counsellors work as part of the professional team providing
      clinical genetic services from regional centres in the United Kingdom. The
      education and training needs of genetic nurses and counsellors have not
      previously been formally identified. The guidelines presented have been devised
      to equip practitioners to fulfil their professional role as defined in a previous
      study, by identifying objectives, educational pathways, and means of assessment.
      While academic courses provide an essential framework, experiential learning in a
      clinical setting is also considered a vital component of the preparation for
      practice.

PMID- 9610806
TI  - The North Cumbria Community Genetics Project.
AB  - The aim of the North Cumbria Community Genetics Project is to establish a store
      of DNA, plasma, and viable cells from a cohort of around 8000 Cumbrian infants.
      To meet this objective, specimens of umbilical cord blood and tissue will be
      collected with maternal consent from babies born at the West Cumberland Hospital,
      Whitehaven over a five year period from January 1996. These samples will be used
      in a series of genetic and epidemiological studies investigating the interaction
      between genes, the environment, and health. There is little population movement
      in West Cumbria and so it will be possible to follow many of the babies
      throughout their childhood and to investigate the relationship between their
      genetic constitution and health outcome.

PMID- 9610807
TI  - Autosomal dominant juvenile recurrent parotitis.
AB  - Juvenile recurrent parotitis is a common cause of inflammatory salivary gland
      swelling in children. A variety of aetiological factors has been proposed for the
      condition. Here we present a family where four members had juvenile recurrent
      parotitis and where two other family members may have had an atypical form of the
      condition. The segregation pattern in the family is consistent with autosomal
      dominant inheritance with incomplete penetrance and this suggests that, at least
      in some cases, genetic factors may be implicated in juvenile recurrent parotitis.

PMID- 9610808
TI  - 49,XXXXY: a distinct phenotype. Three new cases and review.
AB  - Over 100 cases of 49,XXXXY syndrome have been published to date. Classic findings
      include radioulnar synostosis, hypogonadism, and mental retardation. The majority
      of reported cases have not distinguished the 49,XXXXY syndrome from Klinefelter
      syndrome (47,XXY), and these patients are frequently labelled as having
      Klinefelter syndrome or as being a "Klinefelter variant." Because of distinct
      clinical features, we delineate the 49,XXXXY syndrome as separate from
      Klinefelter syndrome, and emphasise the prevalence of congenital heart defects.
      We also report three new cases of 49,XXXXY syndrome and briefly discuss patient
      management.

PMID- 9610809
TI  - Triplication of 15q11-q13 with inv dup(15) in a female with developmental delay.
AB  - A 4 year old female referred with developmental delay was found to have two de
      novo abnormal derivatives of chromosome 15, a supernumerary inverted duplicated
      marker chromosome (inv dup(15)) and an interstitial triplication of proximal
      15q11-q13 or 14 in one of the two 15 homologues (trip(15)). Fluorescence in situ
      hybridisation (FISH) using probes within and flanking the Prader-Willi/Angelman
      syndrome critical region (PWASCR) confirmed the triplication in the abnormal 15
      homologue. The inv dup(15) was dicentric, positive for IR39d which maps proximal
      to the PWASCR, but was negative for all the PWASCR FISH probes used. Results
      using polymorphic microsatellite repeats confirmed that the additional material
      in the trip(15) was maternal in origin and included several PWASCR loci. The
      presence of two de novo abnormalities involving the proximal region of 15q
      suggests a linked mechanism of origin.

PMID- 9610810
TI  - A new family of Greek origin maps to the CRD locus for autosomal dominant cone
      rod dystrophy on 19q.
AB  - Retinal photoreceptor dystrophies (RD) are a highly heterogeneous group of
      genetic disorders of the retina, representing the most frequently inherited form
      of visual handicap, affecting approximately 1.5 million people world wide. To
      date, more than 40 genetic loci have been implicated in RD. One of them, the
      CORD2 locus, for an autosomal dominant form of cone-rod dystrophy (CRD), maps to
      chromosome 19q and has previously been reported in a single large family of
      British origin. We now report a new family with severe early onset CRD,
      phenotypically very similar to the British family, which also maps to 19q, but is
      of Greek origin. Haplotype data of the Greek family showed no recombination
      between and including markers D19S219 and D19S246 and linkage analysis gave a lod
      score of 2.7 (at theta=0) with marker D19S412, confirming the data obtained in
      the British family.

PMID- 9610811
TI  - Exclusion of the familial Mediterranean fever locus as a susceptibility region
      for autosomal dominant familial Hibernian fever.
AB  - Autosomal dominant periodic fevers constitute a range of syndromes characterised
      by recurrent attacks of fever and abdominal pain. Familial Hibernian fever (FHF)
      has been described in only one United Kingdom based family, but two other Irish
      families have been found with similar clinical features. FHF resembles familial
      Mediterranean fever (FMF) in several clinical features, but the mode of
      inheritance of FHF is dominant whereas FMF is recessive. We have investigated
      whether autosomal dominant periodic fevers, in particular FHF, map to the FMF
      susceptibility locus (MEFV) on chromosome 16p13.3. We have used informative
      microsatellite markers flanking this locus to genotype members of the three
      families mentioned above. Two point and multipoint lod scores definitively
      excluded linkage to MEFV in the two larger families. A haplotype study confirmed
      these findings, indicating that FHF is genotypically as well as phenotypically
      distinct from FMF.

PMID- 9610812
TI  - Unknown syndrome: peculiar face, severe hypodontia of permanent teeth, and
      precocious choroid calcifications.
AB  - We describe a mother and her twin daughters affected with severe hypodontia of
      the permanent teeth, precocious calcification of the choroid plexus, and minor
      digital anomalies. The presence of inner telecanthus, broad and flattened nasal
      bridge, mild ocular proptosis, small nose with anteverted nostrils, and slight
      microretrognathia gives them an unusual appearance. All three affected persons
      are of normal intelligence.

PMID- 9610813
TI  - Immunocytochemical demonstration of the expression and induction of manganese
      superoxide dismutase in the adenohypophysis.
AB  - Immunocytochemistry for manganese-superoxide dismutase (Mn-SOD) was studied in 12
      normal adenohypophyses and 38 various pituitary lesions. The proportions of cells
      with granular immunoreactivity for Mn-SOD in normal adenohypophysis ranged from
      9.8% to 29.6% (mean +/- SD; 18.4+/-6.2%). Some positive cells tended to
      accumulate in clusters, distribution of which corresponded well with those
      immunopositive for mitochondrial protein and cytochrome oxidase. The number of Mn
      SOD-positive cells increased in adjacent residual adenohypophysis in eight of
      nine recent infarcts, in two of five old infarcts, in all four cases of
      lymphocytic hypophysitis, in two of four abscess cases and in one of three
      metastatic tumour cases, whereas the immunoreactivities of mitochondrial protein-
      and cytochrome oxidase-positive cells either did not vary or decreased. The
      intensity of the histological inflammatory reactions showed a positive
      correlation with reactivity for Mn-SOD in these lesions. Of eight adenomas, the
      surrounding area of compressed adenohypophysis showed increased numbers of Mn-SOD
      and mitochondrial protein-/cytochrome oxidase-positive cells in four and six
      cases respectively. It is suggested that positivity for Mn-SOD may be related to
      some functional activity of mitochondria. It is further suggested that
      adenohypophysial cells have a high potential to induce Mn-SOD by inflammatory and
      ischaemic stress and, in addition, by enhanced mitochondrial activity.

PMID- 9610814
TI  - Computer-assisted visualization of the rat epididymis: a methodological study
      based on paraffin sections autometallographically stained for zinc ions.
AB  - A concept for the computer-assisted visualization of tubular organs is presented.
      Unmarked histological zinc-stained serial sections from the epididymis of the
      Wistar rat were aligned to demonstrate the concept. Virtual images were made
      through the aligned sections and served as controls for the alignment process.
      Animation of the serial sections and the virtual images revealed new information
      about the structure of the organ under investigation. The analysis was used to
      upgrade the anatomical knowledge of rat epididymis by describing how the
      epididymal duct runs through the structure. The proximal parts of the epididymis
      contain large communicating septa of connective tissue dividing the caput and the
      upper part of the corpus epididymidis into segments. The tortuousness was high in
      the caput with many turns within a small area of the epididymis, whereas longer
      loops were found in the lower part of the corpus and cauda epididymidis. The tube
      of the vas deferens was found to become an integrated part of the ductal system
      in the cauda epididymidis, although it was histologically easy to distinguish
      from the epididymal duct. The total number of cross-sections of the ductus
      epididymidis in the 2254, 15-microm-thick, tissue sections analysed was 104700,
      giving a minimum length of the ductal system of 1.5 m.

PMID- 9610815
TI  - Immunolocalization of myotonic dystrophy protein kinase in corbular and
      junctional sarcoplasmic reticulum of human cardiac muscle.
AB  - The subcellular localization of myotonic dystrophy protein kinase has been
      examined in human cardiac muscles with confocal laser-scanning microscopy and
      electron microscopy. A polyclonal antibody was produced against the synthesized
      peptide from a human kinase cDNA clone. We checked the antibody specificity for
      cardiac myotonic dystrophy protein kinase using an immunoblotting technique.
      Immunoblotting of extract from human cardiac muscles showed mainly 70 kDa and 55
      kDa molecular weight bands. Confocal images of the protein kinase immunostaining
      showed striated banding patterns similar to those of skeletal muscles. In
      addition, the kinase was strongly detected around the intercalated disc.
      Immunoelectron microscopy showed that the kinase was mainly expressed in both
      corbular and junctional sarcoplasmic reticulum, but not in network sarcoplasmic
      reticulum. These results suggest that myotonic dystrophy protein kinase may be
      involved in the modulation of Ca2+ homeostasis in cardiac myofibres.

PMID- 9610816
TI  - The ultrastructure of anionic sites in rat articular cartilage as revealed by
      different preparation methods and polyethyleneimine staining.
AB  - The ultrastructure of anionic sites in the middle layer of rat articular
      cartilages was studied by two methods, the quick-freezing and deep-etching
      method, and the quick-freezing and freeze-substitution method. The anionic sites
      were visualized with a cationic tracer, polyethyleneimine. They were also
      compared with those revealed in tissues subjected to conventional fixation, such
      as pre-embedding or post-embedding. With the deep-etching method, three
      dimensional meshwork structures were observed more clearly in the extracellular
      matrix compared with those seen in conventional ultrathin sections. In
      combination with polyethyleneimine staining, in which no chemical contrast was
      needed for visualization of anionic sites, numerous stained particles were
      detected around filaments in the extracellular matrix, indicating that they were
      anionic sites consisting mainly of proteoglycans. With the pre-embedding method
      and polyethyleneimine staining, the shapes of aggregated stained particles varied
      with different preparation procedures, including chemical fixation and
      contrasting. The fine meshworks were also observed with the post-embedding method
      and polyethyleneimine staining. It is suggested that such images of anionic
      sites, as revealed by the deep-etching method and the post-embedding
      polyethyleneimine-staining method with low-temperature dehydration, are probably
      closer to native states than those revealed by the conventional pre-embedding
      polyethyleneimine-staining method.

PMID- 9610817
TI  - Effect of serotonin on ouabain-sensitive, K+-dependent, p-nitrophenylphosphatase
      activity in strial marginal cells of normal and reserpinized guinea pigs.
AB  - Na+,K+-ATPase activity is abundant on the basolateral infoldings of the strial
      marginal cells and contributes to the maintenance of the characteristic
      electrolyte composition of the endolymph. However, the stria vascularis of the
      cochlea is known not to be innervated. In order to clarify its humoral regulation
      by serotonin, the K+-p-nitrophenylphosphatase activity of strial marginal cells
      was investigated with a cerium-based method in normal guinea pigs and in guinea
      pigs treated with reserpine, 5-hydroxytryptamine or reserpine plus 5
      hydroxytryptamine. K+-p-nitrophenylphosphatase activity was almost completely
      depressed 3-20 days after reserpine administration. Ten days after
      reserpinization, followed by repeated 5-hydroxytryptamine treatment, the enzyme
      activity was detectable. These results suggest that 5-hydroxytryptamine increases
      the phosphatase activity. Thus, the function of the stria vascularis in producing
      cochlear endolymph may be regulated by 5-hydroxytryptamine.

PMID- 9610818
TI  - Evidence that failure of osteoid bone matrix resorption is caused by perturbation
      of osteoclast polarization.
AB  - Osteoclasts resorb bone by a complex dynamic process that initially involves
      attachment, polarization and enzyme secretion, followed by their detachment and
      migration to new sites. In this study, we postulated that mineralized and osteoid
      bone matrix signal osteoclasts differently, resulting in the resorption of
      mineralized bone matrix only. We, therefore, compared the cytoplasmic
      distribution of cytoskeletal proteins F-actin and vinculin using confocal laser
      scanning microscopy in osteoclasts cultured on mineralized and demineralized bone
      slices and correlated the observations with their functional activity. Our
      results have demonstrated significant differences in F-actin and vinculin
      staining patterns between osteoclasts cultured on mineralized bone matrix and
      those on demineralized bone matrix. In addition, the structural variations were
      accompanied by significant differences in bone resorbing activity between
      osteoclasts grown on mineralized bone matrix and those on demineralized bone
      matrix after 24 h of culture --resorption only occurring in mineralized bone but
      not in demineralized bone. These results indicated that failure of osteoid bone
      resorption is caused by perturbation of osteoclast polarization.

PMID- 9610819
TI  - Quantitative immunohistochemical evidence of a functional gradient of chondroitin
      4-sulphate/dermatan sulphate, developmentally regulated in the predentine of rat
      incisor.
AB  - A quantitative examination was carried out on the early and mature stages of
      dentinogenesis in the rat incisor, using a post-embedding immunogold labelling
      with an anti-chondroitin 4 sulphate/dermatan sulphate antibody (2B6). At a very
      early stage of predentine formation, before polarizing odontoblasts have
      established junctional complexes, immunolabelling was weak. In contrast, when
      polarized odontoblasts established distal junctional complexes, immunolabelling
      in predentine was uniform and threefold denser than in initial predentine. The
      same gold particle density was found in the non-mineralized mantle dentine.
      During circumpulpal dentine formation, a gradient was seen in predentine, a
      larger number of gold particles being scored in the proximal zone compared with
      the distal region adjacent to the mineralization front. In circumpulpal dentine,
      some labelling was found within the lumen of the tubules and in the bordering
      dentine around the tubules. A few particles were also detected in intertubular
      matrix after demineralization. Together, these data provide evidence for a
      developmentally regulated gradient during the transition between mantle and
      circumpulpal dentine, and also in a more mature part of the tooth, a functional
      gradient that probably plays a role in the process of mineralization.

PMID- 9610821
TI  - Leriche Memorial Lecture: Presidential address of the International Society for
      Cardiovascular Surgery.

PMID- 9610820
TI  - Enrichment of human bone marrow mononuclear phagocytes and characterization of
      macrophage subpopulations by immunoenzymatic double staining.
AB  - In order to isolate and enrich bone marrow mononuclear phagocytes, we performed
      magnetic-activated cell sorting using beads coupled to a monoclonal antibody
      directed against the monocyte/macrophage surface molecule CD14. Colocalization of
      antigens in single cells was achieved by combining an alkaline phosphatase-anti
      alkaline phosphatase and an avidin-biotin complex immunoassay, avoiding the use
      of peroxidase. Bone marrow macrophages were first labelled by the monoclonal
      antibody PG-M1 (anti-CD68). Subsequently, cytoplasmic and/or surface double
      staining by the monoclonal antibodies against HLA-DR and Mac-2 antigen or the
      lectin GSA-I-B4 was carried out. Whereas HLA-DR was co-expressed by the great
      majority of PG-M1+ macrophages (84.9%+/-6.9%), only a subpopulation exhibited Mac
      2 (69.9%+/-5.9%) antigen or galactoside structures detected by GSA-I-B4 (65.0%+/
      6.7%). The latter result differed only slightly from the percentage of GSA-I-B4+
      macrophages determined in a previous comparative immunomorphometrical study.
      Therefore, using our method of isolation and enrichment by magnetic-activated
      cell sorting, only a negligible portion of macrophages is apparently stimulated,
      as shown by GSA-I-B4 staining. This methodology seems to be a valuable tool for
      further studies on the monocyte-macrophage system.

PMID- 9610822
TI  - The role of the neutrophil in ischaemia-reperfusion injury: potential therapeutic
      interventions.
AB  - The pathogenesis of the reperfusion syndrome is complex and as yet not fully
      elucidated. It is characterized by the development of increased microvascular
      permeability, oedema and tissue necrosis, and is associated with free radical
      release, cellular calcium overload and activation of neutrophils. Furthermore,
      systemic release of putative mediators may result in distant organ injury (lung,
      kidney, heart). This review, after briefly describing the role of neutrophils in
      these events, will concentrate on potential therapeutic interventions that might
      be employed to minimise ischaemia-reperfusion syndrome. Issues of safety will be
      considered, and potential applications of these techniques in patient management
      discussed.

PMID- 9610823
TI  - The role of the monocyte in the generation and dissolution of arterial and venous
      thrombi.
AB  - Monocyte infiltration into forming thrombus has been demonstrated in experimental
      models of venous thrombosis developed in our laboratories. These cells produce
      and release plasminogen activators as the thrombus organises and resolves.
      Monocytes are also capable of assembling and releasing procoagulant factors and
      the evidence for their importance in thrombogenesis is reviewed. The ability of
      monocytes to maintain this fibrinolytic balance suggests that they may have a
      role in both thrombosis and thrombus resolution. Control of the mechanisms which
      regulate these activities may therefore be important in preventing thrombus
      formation or stimulating its resolution.

PMID- 9610824
TI  - Long-term survival after aortic valve replacement for native active infective
      endocarditis.
AB  - BACKGROUND: The objective of this study was to analyse the impact of acute
      surgery for native aortic valve endocarditis and its influence on the long-term
      prognosis after surgery. METHODS: A total of 161 patients underwent aortic valve
      replacement for native active aortic valve endocarditis (NAAVE) during a 29-year
      period, from 1967 to 1995 (age range: 10 to 72 years; mean 48 +/- 12). The main
      indication for surgery was progressive congestive heart failure (76%). Other
      indications were untreatable sepsis (27%), peripheral or central emboli (12%)
      and, from 1978, echocardiographic evidence of friable, pedunculated vegetations
      (3%). Streptococcal and staphylococcal infections predominated. Concomitant
      procedures were performed in 27% of the patients, including mitral and tricuspid
      valve surgery and coronary bypass procedures. RESULTS: Operative mortality was 8%
      in the majority of cases caused by heart failure or multi-organ failure.
      Multivariate logistic regression analysis identified NYHA class IV to be an
      independent predictor for postoperative death. Long-term survival for discharged
      patients was 75% at 10 years and 58% at 15 years, with a mortality rate of
      3.6%/patient/year. Cox regression analysis identified the year of operation,
      trivalvular endocarditis and staphylococcal infection as independent predictors
      of survival. At 10 and 15 years after aortic valve replacement, 91% and 84% of
      the patients, respectively, were free of recurrent endocarditis. The presence of
      an abscess cavity at first operation was found to be predictive of recurrent
      endocarditis. CONCLUSIONS: Valve replacement for NAAVE offers a good chance for a
      cure and satisfactory long-term survival. Improvements in pre- and per-operative
      management of the very ill patient, and the use of allograft valves are likely to
      further improve long-term results. Finally, the presence of staphylococcal
      endocarditis requires long-term postoperative antibiotic therapy.

PMID- 9610825
TI  - Valve replacement in rheumatic mitral incompetence: total versus posterior
      chordal preservation.
AB  - Several studies have shown that mitral valve replacement with total chordal
      preservation (MVR-TCP) improves left ventricular function when compared with
      total chordal transection. Few clinical studies, however, have compared this
      technique to that involving only posterior chordal preservation (MVR-PCP). This
      study was intended to cover this aspect. A total of 36 consecutive patients with
      chronic rheumatic mitral incompetence were operated upon by one surgeon and
      benefited from MVR-TCP (group I). During the same period and along similar
      selection criteria, 60 patients underwent MVR-PCP (group II) in our department.
      With the exception of a statistically significant higher preoperative left
      ventricular ejection fraction (LVEF) percentage and lower fractional shortening
      (LVFS) percentage in group II patients; both groups were comparable as regarding
      age, sex distribution New York Heart Association (NYHA) functional class (FC),
      preoperative left atrial diameter (LAD), left ventricular end-diastolic dimension
      (LVEDD), left ventricular end-systolic dimension (LVESD) as well as aortic cross
      clamp and cardiopulmonary bypass times. The means of the differences, between the
      pre- and postoperative values of NYHA FC and echocardiographic data were compared
      between both groups. As compared with group II, group I patients showed lower:
      hospital mortality rate (0 versus 8.3%; P > 0.05); need for positive inotropic
      support (11.1 versus 20.8%; P > 0.05) and total ICU stay (2.9 +/- 0.17 versus 2.2
      +/- 0.13 days; P < 0.01). In addition, group I patients showed a better NYHA FC
      improvement (-2.08 +/- 0.15 versus -1.93 +/- 0.11; P > 0.05) as well as a
      statistically significant (P < 0.00001) higher decrease in the LAD (-18.19 +/-
      0.97 versus -11.59 +/- 0.58 mm), LVEDD (-14.44 +/- 0.91 versus -6.17 +/- 0.05
      mm), LVESD (-6.17 +/- 0.77 versus -3.23 +/- 0.01 mm), LVFS percentage (-0.06 +/-
      0.01 versus -0.01 +/- 0.001%) and a higher increase in the LVEF percentage (8.1
      +/- 0.9 versus 1.48 +/- 0.02%). The smaller mean diameter of the implanted St
      Jude prosthesis, in group I patients (26.77 +/- 0.22 versus 27.43 +/- 0.21 mm; P
      = 0.046), was neither associated with the use of a smaller prosthesis than that
      predicted for the patient size nor a significantly higher mean transprosthetic
      pressure gradient. These data suggest that in rheumatic patients with chronic
      mitral incompetence, MVR-TCP is always feasible: it is associated with lower
      hospital mortality and morbidity rates and better preservation of the
      postoperative left ventricular systolic functions when compared with MVR-PCP.

PMID- 9610826
TI  - Coronary artery bypass surgery without cardiopulmonary bypass.
AB  - In the years 1994 and 1995, 1087 patients underwent coronary artery bypass
      grafting at our institution. Of these, 297 were operated on without
      cardiopulmonary bypass. 239 were male, and 58 were female. Their ages ranged from
      28 to 81 years (54.43 +/- 9.63). Of the total, 294 were operated on electively,
      two as a coronary reoperations, and one as an emergency after a failed
      percutaneous transluminal coronary angioplasty procedure. In all patients
      complete revascularization was the aim, and a cardiopulmonary bypass team was
      kept on standby. Median sternotomy was performed as the exposure in all patients,
      except a patient who underwent a coronary reoperation through a left thoracotomy
      incision. The average of the distal anastomoses was 1.51 +/- 0.6, ranging from 1
      to 3. The left internal thoracic artery was used in 292 operations, which was an
      individual graft in 284, a sequential graft in five, and a free graft in four.
      Major complications in the early postoperative period were noted in three
      patients as reoperation for excessive bleeding. One patient had reoperation for
      left internal thoracic artery spasm, and one patient had lower extremity ischemia
      caused by intraoartic balloon counterpulsation. Hospital mortality was 0.3% with
      one patient. It is our belief that in selected cases coronary artery bypass
      grafting without cardiopulmonary bypass is a safe procedure with the advantage of
      improvement in recovery during the postoperative period.

PMID- 9610827
TI  - The dose-dependent effects of L-carnitine in myocardial protection in
      normothermic ischemia.
AB  - L-Carnitine has been shown to improve the post-ischemic recovery of myocardial
      function and metabolic measurements that are reduced in the course of ischemia
      and reperfusion of the heart. In this study we used 40 male guinea-pigs in order
      to determine if the effect of L-carnitine which is used in the protection of the
      post-ischemic reperfused heart, is dose-dependent or not. All harvested hearts
      were perfused for 30 min on modified Langendorf apparatus with oxygenized Krebs
      Henseleit solution. After this period, in (n = 10), 5 mmol and 10 mmol (group B,
      n = 10) of L-carnitine were added into a Krebs-Henseleit solution. After 20 min,
      perfusion was complete and the hearts were then exposed to normothermic ischemia
      for 20 minutes. Following the ischemia, hearts were reperfused with the same
      solutions for 30 min. In group C (n = 10), 10 mmol of L-carnitine was added into
      the solution at the post-ischemic reperfusion step. In the control group, the
      same procedures were performed without using L-carnitine. Matching was done
      according to the contractile force of the heart rate and the levels of
      malondialdehyde and adenosine deaminase. When 10 mmol L-carnitine was added into
      the perfusion solutions at the pre-ischemic period, the best results were
      obtained and myocardial damage was much less than the control group. The
      protective effects of L-carnitine in normothermic ischemia is dose-dependent and
      it must be given at the pre-ischemic period.

PMID- 9610828
TI  - Preoperative identification of viable myocardium: effectiveness of nitroglycerine
      induced changes in myocardial Sestamibi uptake.
AB  - In order to predict tissue viability in infarcted myocardial areas, changes
      induced by nitroglycerine infusion on Sestamibi myocardial uptake were evaluated
      in 37 patients with previously confirmed myocardial infarction undergoing
      coronary artery bypass grafting, and compared with echocardiographic and
      perfusional changes occurring after the operation. The improvement of Sestamibi
      uptake after nitroglycerine correctly classified 24/26 (92%) patients showing
      postoperative improvement of wall motion in the infarcted area, whereas 24/31
      (77%) patients with nitroglycerine-induced increase in Sestamibi uptake had
      improved wall motion after operation. The presence of collateral flow to the
      infarcted area was associated with a significantly (P < 0.01) higher increase in
      Sestamibi uptake both during nitroglycerine infusion and postoperatively. An
      increase in wall motion score after operation was associated with a significantly
      higher (P < 0.05) increase in Sestamibi uptake score during nitroglycerine
      infusion. Thus, the results of this study suggest that Sestamibi perfusional
      myocardial scintigraphy during nitroglycerine infusion is capable of assessing
      viable but chronically hypoperfused myocardium and predicting postoperative wall
      motion and perfusional improvement, to yield the best results in patients with
      evidence of collateral circulation that supplies the infarcted area.

PMID- 9610829
TI  - Combined carotid and coronary artery surgery: what have we learned after 15
      years?
AB  - Optimal surgical strategy in patients with concomitant coronary and carotid
      artery disease is debatable. We have analysed 15-years of experience (January
      1981-August 1996) with 195 consecutive patients in whom we have used two
      different surgical approaches. Group A consisted of 48 patients who underwent a
      single-stage surgical procedure, and group B (147 patents) underwent a two-stage
      procedure, either as carotid endarterectomy followed by coronary artery bypass
      surgery (group B1, 97 patients), or as coronary artery bypass surgery followed by
      carotid endarterectomy (group B2, 50 patients). Overall, there were 40 (20.5%)
      patients with left main coronary artery disease, 49 (25.1%) with poor left
      ventricular function, 128 (65.6%) with previous myocardial infarction, 134
      (68.7%) were in New York Health Authority (NYHA) functional class III or IV, and
      bilateral carotid involvement was present in 57 patients (29.2%). Unstable angina
      was more frequent in groups A and B2 (P < 0.0001), NYHA class III-IV was more
      frequent in group A (versus B1, P = 0.001 and versus B2, P = 0.02), low ejection
      fraction (EF) was more frequent in groups A and B2 (P < 0.0001 for both),
      bilateral carotid stenosis in groups A and B1 (P = 0.02 and P = 0.0001,
      respectively) and ulcerated plaque in group B1 (versus A, P = 0.0001). These
      differences dictated the surgical strategy, which resulted in different protocols
      for clinical and operative management. RESULTS: Early mortality for the entire
      group was 4.6% (9/195-6.2% in group A, 6.2% in group B1 and 0% in group B2,
      respectively P > 0.05). Serious morbidity occurred in 7.3% of patients (14/195
      8.3% in group A, 7.2% in group B1 and 6% in group B, respectively P > 0.05).
      Univariate analysis revealed only bilateral carotid stenosis as a predictor of
      outcome (P = 0.04). Follow-up was completed for 156 patients (80.0%) and averaged
      84.1 +/- 13.3 months (range 1-180 months). Kaplan-Meier survival estimate for the
      entire group was 81% and event-free survival was 76% at 5 years. Actuarial and
      event-free survivals were similar for all groups. Early and late outcome in these
      patients were influenced more by their preoperative clinical status than by the
      surgical strategy itself. It is therefore concluded that surgical approach should
      be individualized for the majority of patients.

PMID- 9610830
TI  - Surgery of cavo-atrial renal carcinoma employing circulatory arrest: immediate
      and mid-term results.
AB  - From 1990 to 1995, 12 patients with cavo-atrial renal cell carcinoma underwent
      resection of the tumor. Circulatory arrest was employed in 11/12 cases. The
      neoplasm extended to the inferior vena cava in two patients and to the
      intrahepatic veins or right atrium in five cases. Two severely cardiac
      compromised patients died perioperatively. Of five patients who showed
      preoperative suspicion of isolated metastases, 3 patients died postoperatively
      because of relapsing disease after a mean period of 10.8 months. Five patients
      are alive and doing well after a mean follow-up of 14.8 months. In our experience
      myocardial dysfunction determined poor immediate survival. Mid-term survival was
      influenced by preoperative metastases and lymph-node involvement, but not by
      intracaval extension. Circulatory arrest appears to be a relatively safe
      technique to remove renal carcinoma with cavo-atrial extension and should be
      indicated whenever there are no metastases.

PMID- 9610831
TI  - Management of isolated common iliac artery aneurysms.
AB  - PURPOSE: Since isolated common iliac artery aneurysms are rare and there is no
      consensus regarding some aspects of their management, we reviewed our recorded
      experience with common iliac artery aneurysms from 1977 through 1993. METHODS: We
      were able to identify 25 patients having a total of 33 common iliac artery
      aneurysms on the basis of information maintained by our medical records staff,
      old surgical logs and a departmental registry that was implemented in 1989.
      Follow-up data were collected from outpatient charts and by telephone contact.
      New imaging studies were obtained for 14 patients who either underwent common
      iliac artery aneurysm repair without aortic replacement (aortic ultrasound scans,
      n = 7) or had no surgical treatment whatsoever (computerized tomography of the
      abdomen and pelvis, n = 7). RESULTS: All 25 patients were men (mean age, 71
      years). Eighteen patients (72%) had elective (n = 14) or urgent (n = 4)
      operations to repair common iliac artery aneurysms with mean diameters of 3.8 cm
      and 5.8 cm, respectively. There was one postoperative death (5.5%) in conjunction
      with complementary renal revascularization in a patient with pre-operative renal
      insufficiency. During a mean follow-up period of 50 months, two (29%) of the
      seven patients who had not received bifurcation grafts at the time of their
      common iliac artery aneurysm procedures had developed infrarenal aortic
      aneurysms. Seven (28%) of the original 25 patients were observed without
      intervention for common iliac artery aneurysms measuring 2-2.5 cm in diameter. No
      common iliac artery aneurysm enlargement or new aortic aneurysms have been
      documented in any of these patients at a mean follow-up interval of 57 months.
      CONCLUSIONS: In our limited experience, the risk for spontaneous rupture appears
      to be concentrated among common iliac artery aneurysms exceeding 5 cm in
      diameter, while those that are less than 3 cm in diameter may fail even to
      enlarge under observation. Therefore, common iliac artery aneurysms measuring >
      or = 3 cm in size probably warrant surgical treatment, at which time simultaneous
      aortic replacement also should be a serious consideration.

PMID- 9610832
TI  - Effect of alpha-tocopherol, taurine and selenium on the attenuation of
      ischemia/reperfusion injury of splanchnic organs.
AB  - BACKGROUND: Splanchnic artery occlusion shock is caused by increased capillary
      permeability and cellular injury precipitated by oxygen derived free radicals
      following ischemia and reperfusion of splanchnic organs. The purpose of this
      study was to assess the role of several well-known oxygen-derived free radical
      scavengers in ameliorating or preventing this syndrome. STUDY DESIGN:
      Anesthetized rats were subjected to periods of occlusion of the visceral arteries
      and reperfusion. Tocopherol, taurine, selenium or a 'cocktail' of these three
      agents was injected subcutaneously for 4 consecutive days prior to operation.
      Mean arterial blood pressure was measured throughout the experimental period.
      Fluorometry and technetium-99m pyrophosphate counting of the visceral organs were
      performed as well as a histologic grading system for intestinal viability.
      RESULTS: Final mean arterial blood pressure associated with the 'cocktail' and
      selenium groups was 79.1 +/- 27.4 mmHg and 83.6 +/- 17.8 mmHg, respectively.
      These values were significantly higher than the control group, 40.8 +/- 11.4 mmHg
      (P < 0.05). Similar patterns of the benefit of selenium in contrast with the
      other groups were obtained with fluorescein perfusion, radioisotopic activity and
      histologic analysis. CONCLUSION: Pretreatment with selenium of splanchnic
      ischemia and reperfusion in the rat improves mean arterial blood pressure and
      microcirculatory visceral perfusion. Further analysis of the precise protective
      mechanism of selenium for reperfusion injury will enable visceral organs to
      withstand the consequences of increased capillary leakage and oxidant injury.

PMID- 9610833
TI  - Premature peripheral vascular disease: clinical profile and abnormal lipid
      peroxidation.
AB  - The aim of this study was to determine any biochemical differences between early
      onset peripheral vascular disease and typical onset atherosclerosis, and age
      matched controls. A subset of patients present at a young age ( < 50 years) with
      peripheral vascular disease which pursues an aggressive course. As lipid
      oxidation seems important in atherosclerosis, total lipid peroxides, oxidized
      subfractions, and Trolox equivalent antioxidant capacity (TEAC) were studied in
      patients with premature peripheral vascular disease. Charts were reviewed of
      patients operated on for vascular occlusive disease over a 5-year period.
      Patients with early-onset peripheral vascular disease (group I) were evaluated
      for biochemical abnormalities and compared with typical onset atherosclerotics
      (group II) and age-matched controls (group III). Sixteen patients with early
      onset peripheral vascular disease underwent biochemical evaluation. Conventional
      lipid profiles did not differ statistically from those of age-matched controls,
      except for mild elevations in LDL and VLDL in patients with vascular occlusive
      disease (207 and 195 mg/dl in groups I and 11 versus 157 mg/dl in group III).
      Total oxidative potential was significantly elevated (P = 0.006) 3.04, 2.15 and
      2.04 nmol/ml in groups I, II and III, respectively. Levels of oxidized LDL and
      VLDL were even more significantly elevated (P = 0.0009) for premature peripheral
      vascular disease, (1.2, 0.58 and 0.47 nmol/ml in groups I-II). TEAC values did
      not differ significantly between groups (0.83, 0.82, 0.82 nmol/ml) and did not
      correlate with total lipid peroxide values for individual patients. In
      conclusion, lipid peroxides were significantly elevated in patients with
      premature peripheral vascular disease, the most marked changes being seen in
      oxidized LDL and VLDL subfractions. Lipid peroxides were elevated when standard
      lipid profiles were only mildly abnormal. The poor long-term prognosis in these
      patients suggests the need for aggressive evaluation and treatment of lipid
      abnormalities.

PMID- 9610834
TI  - Endovascular grafting for abdominal aortic aneurysms: changing incidence and
      indication for conversion to open operation.
AB  - The incidence and indications for conversion from endoluminal to open repair of
      abdominal aortic aneurysms are changing. This paper is based on a 5-year
      experience in which endoluminal repair of abdominal aortic aneurysms was
      undertaken in 156 patients. Primary conversion at the original operation was
      required in 14 patients and secondary conversion at a subsequent operation was
      required in 9 patients. The reasons for primary conversion were access problems
      (n = 2), balloon related problems (n = 2), endograft migration (n = 4), endograft
      thrombosis (n = 1) and failed deployment of a bifurcated endograft (n = 5).
      Twelve of 14 primary conversions occurred in the first half of the study period,
      in which 59 endoluminal abdominal aortic aneurysms repairs were undertaken.
      Improvements in technology and interventional techniques for overcoming
      obstacles, as well as increasing experience, has resulted in primary conversion
      being limited to two patients in the most recent 2.5-year period in which 97
      endoluminal repairs were undertaken. The reasons for secondary conversion were
      renal arteries covered by the endograft (n = 2), increasing abdominal aortic
      aneurysm diameter in the absence of endoleak (n = 1) and persistent endoleak (n =
      6). The latter group comprised three patients with intact aneurysms and three
      with known endoleaks who presented with ruptured aneurysms. The current
      indications for primary conversion include: (i) rupture of the aorta; (ii)
      complete migration of the endograft resulting in obstruction of the iliac
      arteries; and (iii) irreversible twisting of a non-modular bifurcated endograft.
      The current indications for secondary conversion include: (i) persistent
      endoleak; (ii) sealed endoleak with continued abdominal aortic aneurysms
      expansion; (iii) apparently successful endoluminal repair without evidence of
      endoleak but continued abdominal aortic aneurysms expansion; and (iv) infected
      endograft.

PMID- 9610835
TI  - Female sex function after aortic surgery.
AB  - OBJECTIVE: To determine the incidence of sexual dysfunction in women after
      abdominal aortic surgery in a questionnaire based study. PATIENTS: A total of 100
      women (aged 46-96, median 75 years) who had aortic grafts during 1990-1994.
      METHODS: Patients were traced and their social circumstances determined. An
      initial approach was made by letter, and questionnaires were sent to women who
      were willing to participate at 1 year or more after their operation. RESULTS:
      Sixty-nine patients were found to be ineligible because they had died (39),
      recently been widowed (15), become seriously unwell or untraceable (15). Of the
      remaining 31, only eight were willing to answer a detailed questionnaire about
      sexual function, and seven did so: four had maintained good sexual function, and
      three had experienced deterioration since surgery (but in two there had been some
      improvement over a period of months). CONCLUSIONS: Assessing any possible effect
      of aortic surgery on sexual function in women is most difficult, because of the
      age and circumstances of many patients, and a general reluctance of patients to
      answer explicit questions about their sexual function. Although this study fails
      to provide any clear evidence of adverse effects, it focuses attention on a
      neglected yet potentially important subject.

PMID- 9610836
TI  - Research initiatives in vascular disease.

PMID- 9610837
TI  - Increased arachidonic acid induced platelet chemiluminescence indicates
      cyclooxygenase overactivity in schizophrenic subjects.
AB  - Platelets were found to emit a burst of chemiluminescence during incubation with
      arachidonic or linoleic acid. This chemiluminescence response may indicate
      activation of the enzyme prostaglandin synthase in the arachidonate-induced
      platelet chemiluminescence as it is inhibited by aspirin. Stimulation of
      platelets with arachidonic acid and linoleic acid induced a concentration
      dependent chemiluminescence response. Platelets from drug naive schizophrenic
      subjects showed significantly increased arachidonic acid metabolism compared to
      control subjects. No significant difference was observed between schizophrenic
      and control subjects in the chemiluminescence response to linoleic acid. In
      schizophrenic subjects treated with neuroleptic drugs the overactive arachidonic
      acid response was normalized. Linoleic acid chemiluminescence response was
      unaffected by neuroleptic treatment. Hyperactive cyclooxygenase activity may
      reflect a similar condition in the brain and implicates prostaglandin pathway
      abnormalities in the pathogenesis of schizophrenia.

PMID- 9610838
TI  - Detection of acyl-CoA synthetase, acyl-CoA:lysophospholipid acyltransferase and
      phospholipase A2 activities in non-pregnant and pregnant guinea-pig uterine
      tissues.
AB  - Acyl-CoA synthetase (ACS), acyl-CoA:lysophospholipid acyltransferase (ACLAT) and
      phospholipase (PL) A2 activities were detected in guinea-pig endometrium on days
      7 and 15 of the cycle, and on days 15, 29 and 36 of pregnancy. Ovariectomy of non
      pregnant animals resulted in an increase in the apparent activities of these
      three enzymes which was reversed by treatment with oestradiol and/or
      progesterone. ACS, ACLAT and PLA2 activities were detected in day 15 conceptuses,
      and in the placenta, sub-placenta, chorion and amnion on days 29 and 36 of
      pregnancy. Apparent activities of the enzymes were generally higher in the fetal
      membranes than in the placental tissue. This study has established that the
      enzymes involved in turnover of arachidonic acid in phospholipids are present in
      tissues in the non-pregnant and pregnant guinea-pig uterus. The higher apparent
      activities of enzymes (ACS and ACLAT) involved in arachidonic acid uptake
      compared to the enzyme (PLA2) involved in arachidonic acid release is in
      agreement with there being very low concentrations of free arachidonic acid in
      tissues.

PMID- 9610839
TI  - Prostanoids counterbalance the bronchoconstrictor activity of endothelin-1 in
      pigs.
AB  - In 12 anaesthetized spontaneously breathing pigs divided into two groups of six
      animals we evaluated the respiratory and haemodynamic responses to endothelin-1
      (ET-1) administered by aerosol (200 pmol x kg(-1) in 1 ml of saline solution). In
      the first group (control group), the responses to ET-1 were evaluated before and
      after the blocking of endogenous nitric oxide (NO) by NG-nitro-L-arginine methyl
      ester (L-NAME 5 mg x kg(-1), i.v.). In the second group (indomethacin-pretreated
      group), the experimental protocol was similar to that of the control group, but
      the responses were evaluated after the blocking of endogenous prostanoids by
      indomethacin (3 mg x kg(-1), i.v.). Results show that in the control group ET-1
      administered before and after L-NAME did not change compliance (Crs) or
      resistances (Rrs) of the respiratory system. In indomethacin-pretreated pigs, ET
      1 significantly increased Rrs and decreased Crs. This constrictor effect
      appearing only during the block of arachidonic acid metabolites showed that ET-1
      activity can be counterbalanced by a release of dilator prostanoids. In this
      group after L-NAME pretreatment ET-1 did not alter the mechanical properties of
      the respiratory system, suggesting an involvement of other bronchodilator
      mechanisms. In the control group, aerosol administered ET-1 increased mean
      systemic (MAP) and pulmonary (MPAP) arterial pressures, while when ET-1 was
      administered after L-NAME pretreatment, MPAP decreased. In the indomethacin
      pretreated group, the peptide did not modify MAP, but caused an early decrease in
      MPAP when administered after L-NAME. Therefore, our results show that ET-1 caused
      a bronchoconstrictor effect only in indomethacin-pretreated pigs and suggest that
      the intrinsic constrictor activity of the peptide can be modulated especially by
      the release of dilator prostanoids.

PMID- 9610840
TI  - Dietary alpha-linolenic acid increases TNF-alpha, and decreases IL-6, IL-10 in
      response to LPS: effects of sesamin on the delta-5 desaturation of omega6 and
      omega3 fatty acids in mice.
AB  - Sesamin (a non-fat portion of sesame seed oil) inhibits delta-5 desaturase
      activity resulting in an accumulation of dihomo-gamma-linolenic acid (DGLA) which
      can displace arachidonic acid (AA) and decrease the formation of pro-inflammatory
      mediators. We investigated the effects of consumption of diets containing 0.25wt%
      sesamin and 15 wt% safflower oil (SO) (providing 12% of the added fat as linoleic
      acid) or a 15 wt% 2:1 mixture of linseed oil and SO (LOSO) (providing 6% alpha
      linolenic acid and 6% linoleic acid) for 3 weeks on the liver membrane fatty acid
      composition and on the production of prostaglandin (PG) E2, TNF-alpha, IL-6 and
      IL10 in mice. Consumption of sesamin-supplemented SO and LOSO diets resulted in a
      significant increase in the levels of 20:3omega6 (DGLA), suggesting that sesamin
      inhibited delta-5 desaturation of omega6 fatty acids. In animals fed LOSO diets,
      the levels of alpha-linolenic acid, eicosapentaenoic acid (EPA) and of
      docosahexaenoic acid (DHA) were elevated with a concomitant decrease of
      arachidonic acid (AA) in the liver membrane phospholipids. Further, in animals
      fed LOSO diets with or without sesamin, an increase in the circulating levels of
      TNF-alpha was associated with a concomitant decrease in PGE2. Despite a lack of
      differences in the levels of AA, the PGE2 levels were significantly lower in mice
      fed sesamin-supplemented SO compared to those fed SO alone. Thus, these data
      suggest that irrespective of the availability of a specific fatty acid as a
      substrate, through regulating the PGE2 synthesis, the production of TNF-alpha
      could be modulated.

PMID- 9610841
TI  - Apoptosis in human primary brain tumours: actions of arachidonic acid.
AB  - It has been postulated that loss of proliferative control in tumour cells is a
      consequence of depletion of cellular arachidonic acid (AA) and that exogenous AA
      and n-6 fatty acids may restore control of proliferation. To test this hypothesis
      and to investigate the activity of AA, apoptosis in human primary brain tumour
      cells was analysed using flow terminal deoxynucleotide transferase uridine nick
      end-labelling (TUNEL). The effect of exogenous AA (30 microM) was analysed in
      collagenase-dispersed tissue from seven human primary brain tumours and in the
      normal brain tissue surrounding one of the tumours. Exogenous AA stimulated
      apoptosis in tumour tissue. A rapid three-fold increase in endonuclease activity
      was detected in tumour cells incubated with AA. The increase in apoptosis was
      significantly greater than the contemporary (< 15%) increase in necrosis detected
      using propidium iodide permeability and was greater than AA effects on normal
      brain tissue. These results are consistent with activation of the pathways of
      apoptosis by AA.

PMID- 9610842
TI  - Effect of carnitine and essential fatty acid supplementation on the uptake of 11C
      carnitine in muscle of a myopathic carnitine-deficient patient using positron
      emission scintigraphy.
AB  - The aim of this study was to demonstrate the pattern of 11C-carnitine uptake
      after various treatment regimens in a myopathic carnitine-deficient patient and
      two normal volunteers, using a whole body counter specially adapted for positron
      emission. One carnitine-deficient patient and two normal volunteers were scanned
      after an intravenous injection of 11C-carnitine, both while on carnitine therapy
      and after discontinuation thereof. The third scan was done on the patient
      following carnitine and fatty acid therapy for 7 days. Both the carnitine
      deficient patient and the normal volunteers showed improved 11C-carnitine uptake
      by thigh muscles after carnitine supplementation, and the carnitine-deficient
      patient even more so after carnitine and fatty acid supplementation. It is
      therefore concluded that the scintigraphic findings support the clinical
      impression that carnitine deficient patients improve after carnitine and
      essential fatty acid supplementation.

PMID- 9610843
TI  - Which prostanoid metabolites should be determined for the study of reproductive
      processes?
AB  - The non-enzymatic metabolites of prostacyclin (PGI2) and thromboxane A2 (TXA2), 6
      keto-prostaglandin F1alpha (6-keto-PGF1alpha) and thromboxane B2 (TXB2), and
      their 2,3-dinor metabolites, 2,3-dinor-6-keto-PGF1alpha and 2,3-dinor-TXB2, were
      measured in early morning urine samples in 24 in vitro fertilization (IVF) cycles
      in 24 women and in 27 women who became pregnant after IVF and embryo transfer
      (ET). The sum of the non-enzymatic metabolites and their 2,3-dinor metabolites
      was considered to be a reflection of total PGI2 and total TXA2 production in
      vivo. Both the ratio of 'total' PGI2/'total' TXA2 and the ratio of the 2,3-dinor
      metabolites were calculated. TXB2 concentrations showed virtually no change and
      the ratios of the non-enzymatic metabolites of PGI2 and TXA2 versus their 2,3
      dinor metabolites remained relatively constant. As a consequence, the ratio of
      2,3-dinor-6-keto-PGF1alpha/2,3-dinor-TXB2 was a close reflection of the ratio of
      'total' PGI2/'total' TXA2, although the latter ratio was significantly higher all
      the time. We conclude that for comparative studies on the balance between PGI2
      and TXA2 in IVF cycles and during gestation, the determination of the 2,3-dinor
      metabolites alone can replace the measurement of all four metabolites.

PMID- 9610844
TI  - 20-HETE mediates the effect of parathyroid hormone and protein kinase C on renal
      phosphate transport.
AB  - Parathyroid hormone (PTH) is a major inhibitor of renal proximal tubule (PT)
      sodium-dependent phosphate (Na+-Pi) cotransport. PTH is thought to exert its
      effect on Pi transport in the PT via the protein kinase A (PKA) and C (PKC)
      intracellular signalling pathways. PKC-dependent phosphorylation of phospholipase
      A2 stimulates arachidonic acid (AA) release, the latter a potent inhibitor of Pi
      transport. In turn, AA is metabolized to 20-hydroxyeicosatetraenoic acid (20
      HETE) in the PT. In addition, 20-HETE production is stimulated by PTH. We
      therefore explored the possibility that 20-HETE may mediate the PTH/PKC
      inhibition of renal Na+-Pi cotransport. To this end, we tested the effect of 20
      HETE on Na+-Pi cotransport in proximal tubule-like cells. Exposure of opossum
      kidney (OK) cells for 4 h to 20-HETE (10(-7) M) decreased Na+-dependent uptake of
      32Pi (from 0.26 +/- 0.02 to 0.19 +/- 0.01 nmol/mg protein.min) by approximately
      25% (P < 0.001). The inhibition was due to a reduction in Vmax. 20-HETE had no
      significant effect on either the apical amiloride-sensitive and insensitive 22Na
      uptakes or on basolateral ouabain-sensitive 86Rb uptake, and was specific for Pi.
      These results indicate that 20-HETE specifically inhibits Na+-dependent Pi
      transport in OK cells and that it may be a mediator of PTH action in the PT.

PMID- 9610846
TI  - Antiatherosclerotic potency of high density lipoprotein of different origins: a
      review and some new findings.
AB  - The antiatherosclerotic potency of isolated high density lipoproteins (HDL) of
      different origins was investigated in three experimental models: (1) isolated HDL
      were injected into cholesterol-rich fed rabbits; (2) the effect of HDL on the
      intracellular level of free and esterified cholesterol as well as on
      proliferation of smooth muscle cells and fibroblasts was investigated in cell
      cultures; and (3) we studied the influence of isolated HDL fractions on
      thromboxane (TXB2) formation in clotting whole blood with different cholesterol
      content.

PMID- 9610845
TI  - Retinoic acid suppresses interleukin-6 synthesis induced by prostaglandins in
      osteoblasts.
AB  - We previously reported that prostaglandin E1 (PGE1) induces the synthesis of
      interleukin-6 (IL-6) via cAMP production in osteoblast-like MC3T3-E1 cells, and
      that, on the other hand, prostaglandin F2alpha (PGF2alpha) stimulates IL-6
      synthesis via activation of protein kinase C. In the present study, we examined
      the effect of retinoic acid on IL-6 synthesis induced by these two prostaglandins
      in MC3T3-E1 cells. Retinoic acid inhibited the IL-6 synthesis induced by
      PGF2alpha or PGE1 in a dose-dependent manner in the range between 0.1 and 10 nM.
      Retinoic acid also suppressed the IL-6 synthesis stimulated by 12-O
      tetradecanoylphorbol-13-acetate, an activator of protein kinase C. The IL-6
      synthesis induced by cholera toxin, forskolin or dibutyryl cAMP was inhibited by
      retinoic acid. However, retinoic acid had little effect on the IL-6 synthesis
      induced by interleukin-1. These results indicate that retinoic acid inhibits IL-6
      synthesis induced by prostaglandins in osteoblasts as follows: the inhibitory
      effect on the PGE1-induced IL-6 synthesis is exerted at a point downstream from
      cAMP, and the inhibitory effect on the PGF2alpha-induced IL-6 synthesis is
      exerted at a point downstream from protein kinase C.

PMID- 9610847
TI  - Influence of diet-modified lipoprotein fractions from rabbits on eicosanoid
      production and on proliferation of rabbit skin fibroblasts.
AB  - Three groups of rabbits received for 8 weeks either ordinary pellets, fish oil
      enriched pellets or a cholesterol-rich (0.5%) diet for modification of
      lipoprotein composition. At the end of the dietary period, low density
      lipoproteins (LDL) and high density lipoproteins (HDL) were prepared from plasma
      of these rabbits. Rabbit skin fibroblasts (RSF) in culture were exposed to these
      isolated LDL and HDL fractions or to human serum albumin (HSA), respectively.
      Eicosanoid release was estimated after stimulation of cells with the Ca ionophore
      A 23187. Exogenous added HDL from the pellet group and HDL from the cholesterol
      fed group as well as HSA stimulated PGI2 production by rabbit skin fibroblasts (P
      < 0.05, respectively) as compared to controls. All LDL preparations investigated
      inhibited PGI2 release from RSF (P < 0.05, respectively). The TXA2 release from
      RSF was increased only by HDL from cholesterol-fed rabbits and by HSA (P < 0.05,
      respectively). Pretreatment of RSF with cholesterol significantly decreased the
      number of detectable cells. Subsequent addition of HDL from the pellet or from
      the fish oil group completely restored the ability of cholesterol-enriched RSF to
      proliferate (P < 0.05, respectively).

PMID- 9610848
TI  - Effects of experimental salt depletion on urinary prostanoid excretions in normal
      women.
AB  - The effects of moderate salt depletion on urinary excretions of prostanoids
      (PG)E2, 6-keto-PGF1alpha (6KPGF) and thromboxane (TX)B2 have been investigated in
      healthy women (SD group, n = 14). Salt depletion was obtained by combining a low
      sodium chloride dietary intake (< 60 mmol per day) with natriuretic and potassium
      sparing treatment. At the end of the treatment, the cumulative sodium deficit was
      438 +/- 42 mmol (mean +/- SEM). Plasma renin activity (PRA) and urinary
      aldosterone excretion were determined in basal conditions. Renal functional
      exploration was performed during hypotonic polyuria (by oral water load) and
      subsequent moderate antidiuresis (by low dose infusion of an antidiuretic hormone
      analogue). In both phases, renal function was estimated by the clearance (cl.)
      method and the urinary concentrations of PGE2, 6KPGF and TXB2 by RIA method. The
      control group was composed of 20 healthy women in normal sodium and potassium
      balance (N group). Salt depletion was effective in increasing the basal values of
      plasma renin activity (PRA) and urinary aldosterone excretion. Moreover, it was
      effective in inducing the following during polyuria: (a) a depression of the
      diuretic response to water load in presence of a reduction in plasma osmolality;
      (b) a reduction in creatinine cl. in the absence of significant changes in mean
      arterial pressure; (c) an increase in the fractional reabsorption of sodium and
      chloride, in particular at the level of the diluting segments. Both in polyuria
      and in antidiuresis, the excretions of 6KPGF and TXB2 were higher in the SD vs. N
      group, while the excretion of PGE2 was not significantly different. In SD and N
      pooled groups, significant positive correlations were shown between basal PRA and
      urinary excretions during polyuria of 6KGPF and TXB2, (but not of PGE2) as well
      as between the excretions of the two metabolites. In conclusion, functionally
      effective salt depletion induces in healthy women a stimulation of renal
      synthesis of both prostacyclin and thromboxane. The excretory data do not give
      evidence of a similar effect on PGE2 synthesis.

PMID- 9610850
TI  - A multilevel analysis of factors affecting the longevity of fixed partial
      dentures, retainers and abutments.
AB  - There is a methodological problem in analysis of data belonging to different
      hierarchical levels, e.g. patient, arch, and tooth. A method for multilevel
      modelling (MLM) that resolves this problem is available. This method which is
      presented in this article, was used to reanalyse previously published long-term
      treatment results concerning the longevity of fixed partial dentures, retainers
      and abutments. The main results were consistent, indicating that no great faults
      were committed when using the conventional logistic regression method. There
      were, however, differences when calculating the combined risks for various
      situations. The conventional method was found to over- and underestimate
      probabilities of survival in different cases, compared to the MLM method.
      Especially when the most negative factors were combined, the conventional method
      had a tendency to underestimate the risk. For example, if an abutment had the
      combination 'endodontically treated'; 'FPD placed by 'another dentist''; 'distal
      abutment'; and 'marginal bone loss > 50%'; the probability of the tooth remaining
      after 18-23 years was only 20% according to the MLM method but 35% according to
      the conventional method. It was concluded that MLM is the method of choice for
      many situations in dental research where data belonging to different levels are
      to be analysed.

PMID- 9610849
TI  - Modulation of eosinophil chemotactic activities to leukotriene B4 by n-3
      polyunsaturated fatty acids.
AB  - Eosinophil accumulation induced by leukotriene B4 appears to be involved in the
      pathogenesis of allergic diseases. We evaluated the effects of docosahexaenoic
      acid (DHA) and eicosapentaenoic acid (EPA) on chemotaxis to leukotriene B4 in
      guinea pig peritoneal eosinophils. Guinea pigs that were sensitized to polymyxin
      B were administered an intraperitoneal injection of polymyxin B (1 mg/animal)
      alone or combined with DHA (15 or 50 mg/kg, i.p.), EPA (50 or 100 mg/kg, i.p.),
      or with linoleic acid (LA) (100 mg/kg, i.p.). Forty hours later, eosinophils were
      obtained from the intraperitoneal lavage fluid and purified. The chemotactic and
      chemokinetic responses of eosinophils to leukotriene B4 were measured using a 96
      well microchemotaxis chamber. DHA significantly decreased the chemotactic and
      chemokinetic responses of eosinophils in a dose-dependent fashion. A higher dose
      of EPA also significantly inhibited both of those responses, whereas LA had no
      effect. Our results suggested a possible mechanism for the improvement of
      allergic diseases by dietary supplementation with n-3 PUFA.

PMID- 9610851
TI  - Methods to improve a periodontally involved terminal abutment of a cantilever
      fixed partial denture--a finite element stress analysis.
AB  - The two-dimensional plane stress finite element stress analysis was used to
      evaluate the stress of mandibular posterior cantilevers for compromised
      periodontal involved distal terminal abutments. Some commonly practiced methods
      to alleviate the stress from mastication of the cantilever FPDs were also
      evaluated. From the analysis the following was concluded: (1) The most distal
      terminal abutment of a cantilever FPD generally experienced a high stress
      concentration. (2) The cantilever FPDs require at least two abutments. Optimum
      stress reduction occurred with a splinting of three abutments. To increase the
      number of abutments to more than three, would not result in a proportional and
      meaningful reduction of stress in the periodontium. (3) To alter the bridge
      material with more rigid material or to have a longer marginal preparation of the
      terminal abutment are ineffective for better stress distribution.

PMID- 9610852
TI  - Gender difference in jaw pain induced by clenching.
AB  - Seven normal male and seven normal female volunteers performed three types of
      biting exercises: an intermittent contraction at maximum voluntary bite force
      (MVBF) to pain intolerance; a ramp intermittent contraction starting at 10% MVBF
      and increasing 10% every 10 s; and a sustained biting at 100% MVBF to pain
      intolerance. The following measurements were made on the first and second days
      before exercise: a pre- and post-exertional overall jaw pain level; maximum pain
      free jaw opening; bilateral masseter pressure pain threshold (PPT) and
      intolerance (PPI). The results showed that only females presented an increased
      overall pain level on the second day and a significant decrease in pain-free jaw
      opening, but no significant decrease of PPT and PPI. These results suggest that
      females respond differently than males to exertional jaw pain, by increasing
      their pain response 24 h later.

PMID- 9610853
TI  - Effect of resin monomer composition on toothbrush wear resistance.
AB  - The purpose of this study was to compare the toothbrush abrasion resistance of
      seven different experimental resins which were made by changing the composition
      of resin monomers. The experimental resins were made by mixing four kinds of
      dental resin monomers (Bis-GMA, UDMA, TMPT and TEGDMA), camphorquinone (1 wt%),
      dimethylaminoethyl methacrylate (2 wt%) and 2,6-di-tert-butyl-p-cresol (0.05
      wt%). The resin specimens were stored in air for 2 weeks, and then put on a
      toothbrush abrasion testing machine. After 100000 strokes, the wear loss of each
      specimen was determined by weight change during the wear test. TMPT-TEGDMA resin
      showed the most wear resistance, while Bis-GMA- and UDMA-based resins showed
      increased wear resistance with an increased content of TEGDMA. Also, a inverse
      relationship between the microhardness number and the amount of wear of the
      respective resins was confirmed.

PMID- 9610854
TI  - The influence of modified cavity design and finishing techniques on the clinical
      performance of amalgam restorations: a 2-year clinical study.
AB  - Use of modified cavo-surface angles (CSAs) and finishing techniques for amalgam
      restorations may influence the long term marginal fracture around these
      restorations. One operator placed 111 Tytin amalgam restorations in Class I and
      II preparations in the permanent teeth of 37 patients, each of whom received
      three restorations. One of these restorations was placed in a cavity prepared
      with a 'traditional' CSA and was finished more than 24 h after placement.
      Prepared cavities for the remaining two restorations for each patient were
      'modified' with the aim of producing an occlusal CSA of 90-110 degrees. One
      restoration was carved-only and the other was finished more than 24 h after
      placement. Clinical evaluation of the restorations was carried out at baseline, 1
      year and 2 years. At these times, the restorations were photographed and stone
      replicas were obtained from impressions taken at the cavity preparation stage to
      determine the cavo-surface angles. Careful application of the modified cavity
      design provided a mean cavo-surface angle of 109 degrees whereas a 'traditional'
      cavity design provided a mean cavo-surface angle of 126 degrees. Using the Mahler
      photographic method of evaluation, a combination of modification of the occlusal
      cavo-surface angle and finishing of the restoration was found to have an
      influence on the marginal fracture at 2 years. The clinical significance of these
      findings, with respect to the modified cavity design, is discussed.

PMID- 9610855
TI  - The effect of noble metals on the mechanical properties of dispersed phase dental
      amalgam.
AB  - The effects of noble metals added as part of a Ag-Cu dispersant on the
      compressive strength and creep of dental amalgams was determined. The Ag-Cu
      eutectic used in high copper dispersant alloy L(0), was altered by adding 15 per
      cent by weight (wt%) of noble metal in place of Ag. In L(1) the noble metal was
      Pd. In L(2), Au and Pd were combined in equal proportions. In L(3), the noble
      metal content was Pd and Pt in equal proportions. A low copper lathe-cut amalgam,
      Aristalloy was used as the matrix. Amalgams S(0) and S(1) had the same
      composition as L(0) and L(1) except that the the low copper alloy matrix was
      Spheralloy, a low copper spherical amalgam. The compressive strength and creep
      were measured according to American Dental Association specification No. 1 and
      the results analysed by ANOVA. The addition of noble metals to the dispersant
      significantly lowered the 1-h compressive strength of amalgams. Compared to the
      control amalgam L(0), the 24-h compressive strength was increased for L(1) and
      L(2) but lowered for L(3). The ADA creep values were significantly lowered by
      addition of all combinations of noble metals. Reported microstructural changes
      such as an increase in unreacted particles, and a slowed setting reaction may
      account for the findings.

PMID- 9610856
TI  - In-vitro solubility of three types of resin and conventional luting cements.
AB  - The solubility of resin luting cement remains unknown although the use of resin
      luting cement for routine cementation of restorations has increased. The purpose
      of this in-vitro study was to compare the solubilities of three resin cements
      currently in clinical use with three brands of conventional luting agents. The
      three resin luting cements, All-Bond C&B (AB, Bisco) Panavia 21 (P21, Kuraray),
      and Super-Bond C&B (SB, Sun-Medical), and the three conventional luting agents,
      Elite Cement 100 (EC, zinc phosphate cement, GC), HY-Bond Carbo-plus Cement (HCP,
      polycarboxylate cement, Shofu), and Fuji I (FI, glass-ionomer cement, GC) were
      used in this study. A modification of the ADA specification test was adopted to
      evaluate the solubilities of luting cements. The two types of media (distilled
      water and pH 4.0 lactic acid solution) in which specimens were stored for 30 days
      were prepared. The four luting cements, EC, FI, AB, and P21, were more soluble in
      lactic acid solution than in distilled water. Resin luting cements were markedly
      less soluble than conventional luting agents when placed in fresh lactic acid
      solution (0.001 mol/L) at pH 4.0 every 24 h over a 30-day period. The solubility
      rates of luting cements could be fitted to mathematical expressions which
      indicated that the solubilities increased linearly or logarithmically with
      immersion period. Fixed prosthodontic restorations cemented with resin luting
      cement may be capable of withstanding long-term clinical use compared with
      conventional luting agents.

PMID- 9610857
TI  - Corrosion behaviour of an indigenous Ag-Sn-Cu cast dental alloy in artificial
      saliva.
AB  - The corrosion behaviour of an indigenous cast alloy of Ag-Sn-Cu, developed for
      crown and bridge prostheses, was studied in artificial saliva, with and without
      the addition of 0.1 M lactic acid, using a potentiostatic technique, and compared
      with that of the standard cast alloy of Ag-Pd (Ney 76). The values of different
      parameters such as corrosion potential and corrosion current density were
      determined for the indigenous alloy of Ag-Sn-Cu and the Ag-Pd alloy. The rate of
      corrosion of the indigenous alloy was found to be relatively higher than that of
      the Ag-Pd alloy up to an applied potential of + 400 mV. However, while the
      indigenous alloy showed a distinct tendency for passivation below + 200 mV at the
      current level of 0.5 mA/cm2 in the artificial saliva (pH 5.7) at 37 degrees C, no
      such tendency for passivation was shown by the Ag-Pd alloy even up to + 400 mV.
      The tendency for passivation by the indigenous Ag-Sn-Cu alloy, however, was not
      shown in the artificial saliva in the presence of 0.1 M lactic acid (pH. 2.7) at
      37 degrees C. Minor variation was observed in the corrosion behaviour of the
      indigenous Ag-Sn-Cu alloys of different grades prepared by alloying elements of
      varying purity.

PMID- 9610858
TI  - A comparative evaluation of mandibular finite element models with different
      lengths and elements for implant biomechanics.
AB  - Further validity of finite element analysis (FEA) in implant biomechanics
      requires an increase of modelled range and mesh refinement, and a consequent
      increase in element number and calculation time. To develop a new method that
      allows a decrease of the modelled range and element number (along with less
      calculation time and less computer memory), 10 FEA models of the mandible with
      different mesio-distal lengths and elements were constructed based on three
      dimensional graphic data of the bone structure around an osseointegrated implant.
      Analysis of stress distribution followed by 100 N loading with the fixation of
      the most external planes of the models indicated that a minimal bone length of
      4.2 mm of the mesial and distal sides was acceptable for FEA representation.
      Moreover, unification of elements located far away from the implant surface did
      not affect stress distribution. These results suggest that it may be possible to
      develop a replica FEA implant model of the mandible with less range and fewer
      elements without altering stress distribution.

PMID- 9610860
TI  - Characteristics of protrusive and lateral excursions of the mandible in children
      with the primary dentition.
AB  - This study characterizes the mandibular protrusive and lateral excursions of
      children with primary dentition. With use of a Selspot system, the protrusive and
      lateral excursions of nine children with the primary dentition and nine adults
      with the permanent dentition were measured and compared. This system was able to
      analyse the simultaneous movements of multiple points on the mandible of a
      subject in three dimensions. Furthermore, the system proved appropriate for use
      in young children because of the small burden imposed on them during the
      measurements. Using this subject-friendly system, the directions of the
      mandibular excursion for five reference points on the mandibular dental arch at
      each measurement distance (i.e. at 0.5 mm intervals) for three projected angles
      (frontal, sagittal and horizontal) were calculated. From the results it was found
      that the excursions of the primary dentition can move more horizontally and more
      forward with small descent compared with the permanent dentition. The underlying
      reason for these findings may be physiological growth, maturation, and adaptation
      of the occlusal function.

PMID- 9610859
TI  - The effect of prosthesis disinfection on salivary microbial levels.
AB  - The aim of this study was to evaluate how the soaking of dentures in a
      disinfection solution affects salivary microbe counts and stomatitis of partially
      dentate patients. Patients soaked their dentures for 4 weeks randomly both in a
      disinfection solution and in a placebo solution. Mutans streptococci,
      lactobacilli and yeast counts were measured before and after each test period and
      also the flow rate, buffer capacity and pH of saliva were registered.
      Disinfection decreased all microbe levels investigated, but only lactobacilli
      counts decreased significantly. Placebo treatment had either no effect on
      salivary microbe counts or they increased slightly. Disinfection caused some
      reduction of the mucosal inflammation under the denture base, but could not
      completely remove stomatitis during the 4-week test period.

PMID- 9610861
TI  - The use of interferon-alpha in the treatment of cutaneous melanoma: a review.
AB  - During the past few years significant progress has been made in the treatment of
      cutaneous melanoma. These developments often involve the use of interferon-alpha
      (IFNalpha). Promising results have been reported in high risk patients using
      adjuvant treatment with high dose IFNalpha. A confirmatory trial of high dose
      IFNalpha and several adjuvant trials using low or intermediate dose IFNalpha are
      ongoing, and currently a standard regimen cannot be defined. High response rates
      have been reported in patients with metastatic disease with combination
      chemoimmunotherapy schedules. Randomized trials have to be performed in order to
      demonstrate a survival benefit over less toxic regimens. In this paper the
      current status of IFNalpha in the treatment of cutaneous melanoma is reviewed.

PMID- 9610862
TI  - Comparison of antimelanoma effects of 4-S-cysteaminylphenol and its homologues.
AB  - 4-S-Cysteaminylphenol (4-S-CAP), a phenolic thioether, has been evaluated for
      melanocytotoxicity. We have recently shown that dihydro-1,4-benzothiazine-6,7
      dione (benzothiazine BQ) is the ultimate toxic metabolite produced by tyrosinase
      oxidation of 4-SCAP. In this study we compared the antimelanoma effects of 4-SCAP
      and its two homologues, alpha-methyl-4-S-cysteaminylphenol (alpha-Me-4-SCAP) and
      4-S-homocysteaminylphenol (4-S-Homo-CAP). Biochemical experiments showed that
      upon tyrosinase oxidation alpha-Me-S-CAP and 4-S-Homo-CAP also produced
      homologues of BQ which reacted rapidly with reduced glutathione (GSH) and also
      inhibited alcohol dehydrogenase, an SH enzyme. In vitro experiments showed that 4
      S-CAP and its two homologues were taken up into B16-F1 melanoma cells at
      comparable rates but that 4-S-Homo-CAP was least effective in GSH deprivation,
      which was reflected in the low cytotoxicity of this phenol, and that the
      cytotoxicity of the phenols was tyrosinase dependent, as proved by the negligible
      effects on B16-G4F cells which have a much lower tyrosinase activity. In vivo
      experiments showed that direct intratumoral administration of these phenols
      inhibited the subcutaneous growth of B16 melanoma, with 4-S-Homo-CAP being the
      least effective, and that indirect Intraperitoneal administration of 4-S-CAP
      inhibited melanoma growth much more effectively than the two homologues. These
      results indicate that 4-S-CAP is the most promising antimelanoma agent among the
      three phenols examined.

PMID- 9610863
TI  - Melanoma cell growth inhibition and melanocortin receptor downregulation induced
      by selective and non-selective retinoids.
AB  - The purpose of this study was to investigate the effects of retinoid analogues
      with different retinoid receptor specificity on the growth of human D10 and
      Cloudman S91 mouse melanoma cells. We compared the growth inhibitory effects with
      the ability of retinoids to downregulate cell surface expression of the
      melanocortin receptor (MC1-R). Retinoic acid receptor (RAR)-gamma-selective
      retinoids exerted the most prominent growth effects, with up to 68% and 69%
      inhibition in D10 and S91 cells, respectively. A retinoid X receptor (RXR)
      selective compound inhibited cell growth by only 14% and 23% in D10 and S91
      cells, respectively. Growth inhibition by RARalpha- and RARbeta-selective
      compounds was below 10% in both cells. In D10 cells, MC1-R downregulation was
      also induced most effectively by an RARgamma-selective retinoid (84% relative to
      controls). RARalpha-, RARbeta-and RXR-selective agonists induced only 16-24% MC1
      R downregulation in these cells. The pattern for MC1-R downregulation was
      completely different in S91 cells. The RXR-selective compound was the most active
      (85%), followed by the RARalpha-selective agonist (58%), the RARgamma-selective
      compound (47%), and finally by the RARbeta-selective agonist (29%). We conclude
      that RARgamma-selective retinoids may have potential as therapeutic agents in
      melanoma. Different selectivity profiles for growth inhibition and MC1-R
      downregulation in S91 cells suggest that these two retinoid effects are not
      directly dependent on each other.

PMID- 9610864
TI  - Melanoma-cell toxicity of cystemustine combined with O6-benzyl-N2
      acetylguanosine.
AB  - Cystemustine (N'-(2-chloroethyl)-N-(2-(methylsulphonyl)ethyl)-N'-nitrosourea) is
      a new chloroethylnitrosourea (CENU) being used in phase II clinical trials of
      disseminated melanoma. Clinical results show that tumour regression has only been
      observed in 25% of melanomas treated by CENUs. Tumour resistance to CENU is known
      to be mainly due to a DNA repair protein, O6-methylguanine-DNA methyltransferase
      (MGMT). The poor remission rate of melanoma with CENUs is attributed to the fact
      that metastases contain high MGMT levels. Previously, we have shown that O6
      benzyl-N2-acetylguanosine (BNAG), an MGMT inhibitor, can be combined with
      cystemustine by intravenous administration, and increases the antitumour effect
      of cystemustine in resistant human melanoma. In the work presented here, we
      investigated the in vitro pharmacological effect of this combination on the DNA
      of human melanoma cells (M3Dau cells). A quantitative polymerase chain reaction
      (QPCR) assay was used to measure DNA damage in a fragment (2.7 kb) of the hprt
      gene. The results show that treatment with BNAG enhances the number of lesions in
      the DNA of cystemustine-treated resistant malignant melanocytes, which may
      account for the high tumour-cell toxicity of the combination of cystemustine and
      BNAG.

PMID- 9610865
TI  - Inhibition of melanoma pulmonary metastasis by methylxanthines due to decreased
      invasion and proliferation.
AB  - Theophylline- and caffeine-treated B16-F10 cells exhibited low adhesion to
      laminin/collagen type IV and reduced invasion through Matrigel in an in vitro
      assay. In contrast, theobromine appeared ineffective. When young adult C57BL/6
      mice were injected intravenously with theophylline-treated B16-F10 cells, the
      number of surface lung tumours was markedly reduced. Densitometric analyses
      performed on digitalized microscopic images of histological sections of lung were
      used to estimate the frequency (number of lung foci; NLF) and the size (average
      area of metastatic foci; AMF) of the resulting tumour foci. These parameters were
      correlated to the proliferation (AMF) and invasion (NLF) of melanoma cells in
      vivo. The data showed a similar theophylline-induced decrease in the AMF and NLF
      values (71%, P < 0.01). Caffeine treatment produced a more pronounced decrease in
      the AMF (61%, P < 0.01) than in the NLF (25%, P < 0.01). To our knowledge, this
      is the first demonstration that theophylline and caffeine possess the capacity to
      inhibit not only cell proliferation, but also the metastatic behaviour of
      melanoma cancer cells.

PMID- 9610866
TI  - The prognostic significance of c-myc oncogene expression in uveal melanoma.
AB  - The role of the c-myc oncogene has been little investigated in uveal melanoma. In
      this study an analysis of c-myc oncoprotein expression was undertaken using flow
      cytometry in 71 patients with posterior uveal melanoma. Nuclear c-myc oncoprotein
      was detected in all of the tumours, and survival analysis revealed a significant
      association between high oncoprotein positivity and improved survival (log rank
      test: chi2 = 6.47, P = 0.01). Multifactorial analysis using Cox's proportional
      hazards model revealed nuclear c-myc oncoprotein to be an independent prognostic
      marker more accurate than other clinicopathological parameters (log rank test:
      chi2 = 6.61, P = 0.01). However, this result of high oncoprotein expression
      correlating with improved outcome is surprising and in contrast to our previous
      studies using the same method on cutaneous melanoma, where high levels of nuclear
      c-myc expression have been found to correlate with poor outcome both in primary
      and secondary disease. This study suggests that the pattern of oncogene
      expression in uveal melanoma is distinct from cutaneous melanoma and that the
      underlying biology of these tumours is different.

PMID- 9610867
TI  - DNA damage in peripheral blood mononuclear cells correlates with response to
      biochemotherapy in melanoma.
AB  - The combination of cisplatin-based chemotherapy with interleukin-2 (IL-2) and
      interferon, referred to as biochemotherapy, has shown encouraging results in
      patients with advanced melanoma. Toxicity is high, however and no objective
      parameters exist to distinguish between patients who are likely to respond and
      those who are not. The purpose of this pilot study was to determine whether in
      vitro cisplatin-induced damage to the glutathione S-transferase-pi (GST-pi) gene
      in peripheral blood mononuclear cells (PBMCs) before therapy correlated with the
      histological response in melanoma patients with local-regional metastases who
      received concurrent biochemotherapy before definitive surgery. Before therapy,
      PBMCs from 16 patients were exposed to cisplatin at concentrations of 25, 50 or
      100 microM for 3 h and the extent of damage to the GST-pi gene was quantitated by
      polymerase chain reaction (PCR). Patients were subsequently treated on a
      biochemotherapy regimen consisting of cisplatin 20 mg/m2 intravenously (i.v.) on
      days 1-4, vinblastine 1.5 mg/m2 i.v. on days 1-4, dacarbazine 800 mg/m2 i.v. on
      day 1, IL-2 9 MIU/m2 per day i.v. by continuous infusion on days 1-4 (total of 96
      h), and interferon alpha2a 5 MU/m2 subcutaneously on days 1-5. The 16 patients
      were categorized into two groups: major responders (n = 7) and non-major
      responders (n = 9). Although we observed a wide interpatient variation, a
      statistically significant correlation existed between the histological response
      and the degree of DNA damage caused in the PBMCs at all three cisplatin
      concentrations tested (P = 0.024 for 25 microM; P = 0.036 for 50 microM; P =
      0.007 for 100 microM). Our pilot study suggests that determination of in vitro
      cisplatin-induced DNA damage using a gene-specific PCR assay may be useful in
      predicting the histological response to biochemotherapy.

PMID- 9610868
TI  - Nitric oxide and neopterin levels and clinical response in stage III melanoma
      patients receiving concurrent biochemotherapy.
AB  - The combination of cisplatin-based chemotherapy with interleukin-2 (IL-2) and
      interferon-alpha (IFN-alpha), referred to as biochemotherapy, has produced
      overall response rates of greater than 50% in advanced melanoma patients, with
      durable complete responses in the range of 5-10%. The mechanism of action of
      biochemotherapy is unknown. Preclinical work suggests synergistic interactions
      between the cytotoxic agents, especially cisplatin, and the biological agents in
      killing melanoma cells. Immune effector cells activated by the components of the
      biochemotherapy may also be involved, as direct cytotoxic effectors and/or as
      sources of secondary cytokines, which can induce nitric oxide (NO) production in
      a wide variety of cell types. In addition, high levels of neopterin, a marker of
      monocyte/macrophage activation, have been found in patients undergoing
      immunotherapy or biochemotherapy for melanoma. Based on these data, we
      hypothesized that the degree of elevation of serum NO metabolic products and
      neopterin during treatment would correlate with the response to biochemotherapy
      in melanoma patients. Blood samples were obtained before and during preoperative
      biochemotherapy with cisplatin, vinblastine, dacarbazine, IL-2 and IFN-alpha in
      45 melanoma patients with locoregionally advanced disease. NO was measured as
      nitrite after enzymatic reduction, using the colorimetric assay of Griess, and
      neopterin was measured by radioimmunoassay. Our results demonstrate a higher day
      5 nitrite level (of borderline statistical significance, P = 0.057) in major
      responders to the therapy than in those who did not achieve a major response,
      while there was no difference in the elevation in neopterin level during therapy
      between major and non-major responders. These results suggest that induction of
      NO during biochemotherapy may be playing a role in the mechanism of action of
      this therapy, while the role of monocyte/macrophage activation is still in
      question.

PMID- 9610869
TI  - Multiple agminate Spitz naevi.
AB  - We report two patients with multiple agminate Spitz naevi (MASM), a rare
      disorder. In case 1, a 16-year-old girl, the results of chromosomal investigation
      of fibroblasts from the affected area (translocation 45, X, t(4; 7) (p14; p22) in
      a mosaic pattern) suggest that early during embryogenesis a de novo reciprocal
      translocation has occurred between chromosomes 4 and 7. This resulted in the skin
      lesions as described on the right shoulder, arm and hand. The melanoma risk in
      MASM is also discussed.

PMID- 9610870
TI  - Incorporation of pre-existing collagen bundles in primary cutaneous melanoma.
AB  - In a previous qualitative study it has been shown that the incorporation of pre
      existing collagen bundles from the reticular dermis into the bulk of melanoma
      lesions metastatic to the skin indicates rapid systemic spread. In the present
      study the amount of pre-existing dermal collagen in the bulk of the melanoma
      lesions in 267 cases of primary melanoma of the skin with a Clark level of at
      least III was quantitatively assessed using automated image analysis based on RGB
      (red, green and blue) colour images of sections stained with haematoxylin and
      eosin. There was a weak correlation between the amount of pre-existing collagen
      and the Clark level and the Breslow index. With regard to prognosis, a large
      amount of pre-existing collagen (> 0.13 mm2 per index slide) was significantly
      associated with a particularly poor outcome (24-month survival rate: 71 +/- 17%
      compared with 96 +/- 2%; log rank test: P < 0.001). It is clear that a large
      amount of pre-existing collagen bundles occurring as a particular feature of
      tumour-stroma interaction indicates high metastatic capacity in primary malignant
      melanoma.

PMID- 9610871
TI  - Combined treatment of stage IV melanoma patients with amifostine and fotemustine-
      a pilot study.
AB  - Amifostine (Ethyol) is a new chemoprotective agent that has been shown to have
      significant activity in the prevention of nephro-, oto-, neuro- and
      haemotoxicity. In preclinical models as well as in clinical trials carried out in
      patients suffering from various malignancies, the adverse effects and signs of
      toxicity related to a number of cytostatic drugs, including cisplatin,
      cyclophosphamide, carboplatin and mitomycin C, were prevented. In Europe
      fotemustine (Muphoran) is widely used in the treatment of brain metastases in
      melanoma patients. However, the dose is often limited by severe bone marrow
      toxicity after induction cycles, particularly in heavily pretreated patients. In
      order to test whether amifostine treatment might promote bone marrow protective
      effects when combined with fotemustine chemotherapy, we conducted a preliminary
      study in 10 patients suffering from stage IV disseminated malignant melanoma. The
      patients received amifostine (740 mg/m2) prior to fotemustine chemotherapy (100
      mg/m2). Six of the patients had failed one or two other prior chemotherapy
      regimens. Seven patients had brain metastases. Among the 10 patients treated with
      amifostine and fotemustine, no major clinical responses (complete response or
      partial response) were achieved, with four patients showing stabilization of the
      disease over more than 3 months. No patient in the amifostine plus fotemustine
      treatment group showed severe myelosuppression (WHO grade III/IV), in contrast to
      a historical control group treated with fotemustine alone, in which about 40%
      developed major thrombocytopenia and about 45% developed severe leucopenia (WHO
      grade III/IV). Therefore, we conclude that the combination of amifostine with
      fotemustine was well tolerated in this small series of patients and further
      studies are warranted to test the amelioration of myelosuppression by the
      addition of amifostine.

PMID- 9610872
TI  - Combined treatment with dacarbazine, cisplatin, fotemustine and tamoxifen in
      metastatic malignant melanoma.
AB  - The combination of dacarbazine (DTIC), cisplatin (DDP), carmustine and tamoxifen
      (TAM) has been reported to yield a high rate of response in patients with
      metastatic melanoma, but responders often experience intracranial recurrences. As
      fotemustine (FOT) has demonstrated activity on cerebral metastases, the rationale
      of this study was to replace carmustine by FOT in this four-drug regimen. Twenty
      patients with metastatic melanoma received FOT (100 mg/m2) on days 1 and 8, DTIC
      (220 mg/m2 per day) and DDP (25 mg/m2 per day) from day 1 to day 3 and from day
      28 to day 30, and continuous daily treatment with TAM (20 mg/day). If
      stabilization or response was observed at the end of the 8th week, patients
      received maintenance courses of FOT on day 1, and DTIC (220 mg/m2 per day) and
      DDP (25 mg/m2 per day) on days 1 to 3. Nineteen patients were evaluable. Of
      these, six had brain metastases. The overall response rate was 10.5% (two out of
      19); both of the responders had only partial responses. The best responding site
      was lung. No response was obtained in the four patients with evaluable brain
      metastases, but no patient had therapy failure due to new brain metastases. The
      median overall survival was 5 months (range 1-45 months). Toxicity was mainly
      haematological. The use of this combination is not recommended.

PMID- 9610873
TI  - Occurrence of cutaneous and uveal melanoma in patients with uveal melanoma and
      their first degree relatives.
AB  - Uveal and cutaneous melanomas are rare tumours, but have been described to occur
      together in one patient or in members of the same family. A group of 109
      consecutive uveal melanoma patients from one specialized ocular tumour clinic
      were investigated dermatologically. The patient's own history and medical data
      and the family history of skin or eye problems were recorded. A total of three
      cutaneous melanomas were found as a result of this study--two in ocular melanoma
      patients and one in a first-degree relative. Four patients had first-degree
      relatives with a skin melanoma (in three of these families dysplastic naevus
      syndrome was also found), and one patient had a first-degree relative with an
      uveal melanoma. To find cutaneous and uveal melanoma coexisting in two cases and
      cutaneous melanoma in first-degree relatives in four cases out of a total of 109
      uveal melanoma patients seems more than a coincidence. A linking factor in three
      cases was the familial atypical multiple mole melanoma syndrome, suggesting a
      common genetic predisposition to both malignancies in these families. In our only
      family with familial uveal melanoma, cutaneous melanoma and atypical naevi did
      not occur. A different genetic mechanism for these cases is probable.

PMID- 9610874
TI  - Extent and consequences of physician delay in the diagnosis of acral melanoma.
AB  - The extent and consequences of professional delay in diagnosis were analysed in
      83 patients with palmoplantar and subungual melanomas treated from January 1986
      to March 1997 in our department. Seventeen (52%) out of 33 subungual melanomas
      and 10 (20%) out of 50 palmoplantar melanomas were clinically misdiagnosed by
      physicians. Three palmoplantar melanomas (6%) were initially misinterpreted by
      pathologists. In 23 of the 27 cases (85%) the clinical misdiagnosis was made by
      non-dermatologists. Misdiagnosis caused a median delay of 12 months in the
      diagnosis of palmoplantar melanomas and 18 months in the diagnosis of subungual
      melanomas. Delay in diagnosis was associated with increased tumour thickness,
      more advanced stage at time of melanoma diagnosis and a lower estimated 5-year
      survival rate (15.4% versus 68.9% for palmoplantar; 68.5% versus 90.9% for
      subungual). Acral melanomas are frequently misdiagnosed due to their less common
      locations and because plantar and subungual melanomas often do not fit the
      'changing mole' pattern. To Improve the patient's prognosis it is necessary to
      increase the physicians' skill in the diagnosis of acral melanomas. Histological
      examination should always be performed in acral lesions that do not heal.

PMID- 9610875
TI  - Malignant melanoma associated with human immunodeficiency virus infection: a case
      report and review of the literature.
AB  - A case of malignant melanoma arising in a young patient suffering from human
      immunodeficiency virus (HIV) infection is reported, along with a review of the
      literature. The neoplasm was characterized by aggressive clinical behaviour and,
      histopathologically, by a peculiar retiform pattern of growth with neoplastic
      cells interspersed among collagen bundles in the dermis without evident
      fibroplastic stromal reaction. In addition, a complete absence of host
      inflammatory cell infiltrate was noted. We hypothesize that this unusual
      histopathological pattern of growth, which has never been reported in this
      clinical setting, might be associated to HIV disease, immunosuppression and poor
      clinical outcome.

PMID- 9610876
TI  - The lack of methods for assessment of natural and artificial ultraviolet exposure
      in the population.

PMID- 9610877
TI  - Development and evolution in nervous systems: development and evolution of ideas.

PMID- 9610878
TI  - Regeneration in the CNS: optimism mounts.

PMID- 9610879
TI  - Synaptic tagging: implications for late maintenance of hippocampal long-term
      potentiation.
AB  - A novel property of hippocampal LTP, 'variable persistence', has recently been
      described that is, we argue, relevant to the role of LTP in information storage.
      Specifically, new results indicate that a particular pattern of synaptic
      activation can give rise, either to a relatively short-lasting LTP, or to a
      longer-lasting LTP as a function of the history of activation of the neuron. This
      has led to the idea that the induction of LTP is associated with the setting of
      a'synaptic tag' at activated synapses, whose role is to sequester plasticity
      related proteins that then serve to stabilize temporary synaptic changes and so
      extend their persistence. In this article, we outline the synaptic tag
      hypothesis, compare predictions it makes with those of other theories about the
      persistence of LTP, and speculate about the cellular identity of the tag. In
      addition, we outline the requirement for aminergic activation to induce late LTP
      and consider the functional implications of the synaptic tag hypothesis with
      respect to long-term memory.

PMID- 9610880
TI  - Language within our grasp.
AB  - In monkeys, the rostral part of ventral premotor cortex (area F5) contains
      neurons that discharge, both when the monkey grasps or manipulates objects and
      when it observes the experimenter making similar actions. These neurons (mirror
      neurons) appear to represent a system that matches observed events to similar,
      internally generated actions, and in this way forms a link between the observer
      and the actor. Transcranial magnetic stimulation and positron emission tomography
      (PET) experiments suggest that a mirror system for gesture recognition also
      exists in humans and includes Broca's area. We propose here that such an
      observation/execution matching system provides a necessary bridge from'doing'
      to'communicating',as the link between actor and observer becomes a link between
      the sender and the receiver of each message.

PMID- 9610881
TI  - 1898: the Golgi apparatus emerges from nerve cells.
AB  - A century ago, Camillo Golgi discovered in neurons an intracellular network of
      anastomosing threads, impregnated by the chromoargentic reaction he had devised
      to stain the nervous tissue. This structure, designated by Golgi as 'internal
      reticular apparatus', was soon detected in a wide variety of eukaryotic cells.
      However, skepticism arose on the existence of the Golgi apparatus in the first
      decades of this century, when it was fiercely debated whether this structure
      represented a genuine new cell constituent or an artifact due to the deposit of
      metallic impregnation on diverse cytoplasmic structures. The reality of the Golgi
      apparatus became established unequivocally only with the application of electron
      microscopy; with the visualization of its fine structure, the apparatus finally
      achieved the status of cytoplasmic organelle, and thus, linked with Golgi's name,
      entered the modern era of investigation on its components, chemistry and
      function.

PMID- 9610882
TI  - The amygdala: myth or monolith?

PMID- 9610883
TI  - The function of consciousness.

PMID- 9610884
TI  - The effects of steroid hormones on electrical activity of excitable cells.
AB  - Steroid hormones influence the electrical activity of many neurons and effectors
      by regulating the transcription of their ion channels and neurotransmitter
      receptors, or by modulating the activity of their channels and receptors through
      second messenger-coupled membrane receptors, or both. In this article, four cell
      types with known functions and distinct electrical activities are focused on to
      illustrate how different steroids act synergistically with, or in opposition to,
      each other to modulate specific electrical phenomena such as spontaneous regular
      firing (GH3 cells, a pituitary cell line), action potential duration (electric
      organ cells), and intrinsic excitability and sensitivity to neurotransmitters
      (GnRH and opioidergic neurons).These examples illustrate how steroids might
      influence electrical activity in neurons involved in more complex central
      circuits.

PMID- 9610885
TI  - Extracellular space structure revealed by diffusion analysis.
AB  - The structure of brain extracellular space resembles foam. Diffusing molecules
      execute random movements that cause their collision with membranes and affect
      their concentration distribution. By measuring this distribution, the volume
      fraction (alpha) and the tortuosity (lambda) can be estimated. The volume
      fraction indicates the relative amount of extracellular space and tortuosity is a
      measure of hindrance of cellular obstructions. Diffusion measurements with
      molecules <500 Mr show that alpha approximately 0.2 and lambda approximately 1.6,
      although some brain regions are anisotropic. Molecules > or =3000 Mr show more
      hindrance, but molecules of 70000 Mr can move through the extracellular space.
      During stimulation, and in pathophysiological states, alpha and lambda change,
      for example in severe ischemia alpha = 0.04 and lambda = 2.2. These data support
      the feasibility of extrasynaptic or volume transmission in the extracellular
      space.

PMID- 9610886
TI  - Orphanin FQ/nociceptin: a role in pain and analgesia, but so much more.
AB  - The publication of the delta opioid receptor sequence led to the cloning of three
      homologous receptors: the mu and kappa opioid receptors, and a novel opioid-like
      orphan receptor. The orphan receptor's endogenous ligand, a 17-amino-acid peptide
      that resembles dynorphin, was named 'orphanin FQ' and 'nociceptin' (OFQ/N1-17).
      The OFQ/N1-17 receptor is expressed widely in the nervous system, and it is
      becoming clear that the peptide is likely to participate in a broad range of
      physiological and behavioral functions. At the cellular level, OFQ/N1-17 has much
      in common with the classical opioids; however, functional studies are now
      revealing distinct actions of this peptide. Identified only two years ago, OFQ/N1
      17 has already attracted a great deal of attention. The number and diversity of
      papers focused on OFQ/N1-17 at the recent meeting of the Society for Neuroscience
      augur an exciting future for this new peptide.

PMID- 9610887
TI  - Increased diameters of collagen fibrils precipitated in vitro in the presence of
      decorin from various connective tissues.
AB  - Proteoglycans were isolated from bovine skin, sclera, deep flexor tendon and the
      periphery of the temporomandibular joint disc with urea. Decorin was purified
      from each of these extracts by ion-exchange, hydrophobic-interaction and gel
      filtration chromatography. Purities were assessed by amino acid analysis and by
      sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS-PAGE) of the
      protein cores released by digestion with chondroitin-ABC-lyase. In these respects
      the decorins were indistinguishable. However the glycosaminoglycan chains
      released by digesting the proteoglycans with papain varied widely in mobility on
      SDS-PAGE: that from skin decorin migrating fastest and that from tendon decorin
      slowest. The effects of each of the decorins on collagen fibrillogenesis in vitro
      were similar, all reducing the rate of fibril growth (by 55 to 71%, depending on
      the source of the proteoglycan) and increasing the diameters of the fibrils
      formed (by 27 to 66%). Core protein alone, isolated from skin decorin, reduced
      the rate of fibril growth as effectively as intact decorin, but had no effect on
      the diameter of fibrils formed. The dermatan sulphate chain and the protein thus
      appear to play different roles in the interaction of intact decorin with
      collagen. These data suggest that decorin found in fibrous connective tissues may
      increase Type I collagen fibril diameters, resulting in tissues that are better
      able to withstand tensile forces.

PMID- 9610888
TI  - The contributions of glycosaminoglycans, collagen and other interstitial
      components to the hydraulic resistivity of porcine aortic wall.
AB  - A pressure-driven flux of water occurs across the arterial wall in vivo. We have
      investigated the role of several interstitial components in determining the
      resistance of the wall to this flow. Pieces of porcine thoracic aorta were
      modified by thermal denaturation, enzymatic digestion or disruptive chemical
      treatments. The effect of these procedures on the wall content of
      glycosaminoglycans, collagen and elastin was determined by biochemical assay of
      uronic acid and hydroxyproline. Effects on hydraulic conductivity were measured
      by using a flow cell in which tissue was free to deform under applied pressure.
      Untreated tissue showed considerable variation in uronic acid content but
      conductivities were substantially less variable and averaged 0.75 x 10(-12)
      cm4/dyne.s. In tissue autoclaved for < 1 h, resistivity increased, possibly
      because interstitial components had been denatured but not removed from the wall.
      After longer periods, resistivity decreased by a factor of one hundred. More
      specific treatments showed that resistivity decreased by up to a factor of ten
      when glycosaminoglycans were removed and by a similar factor when collagen was
      removed. Tissue in which both were removed showed a hundred-fold decrease in
      resistivity. As with tissue subjected to prolonged autoclaving, the resistivity
      was still an order of magnitude higher than that of alkali- or acid-extracted
      elastin despite an apparently similar composition, suggesting the existence of a
      non-assayed component with important properties. The resistivity of the samples
      was decreased further by treatment with chymotrypsin, consistent with this
      component being microfibrillar protein.

PMID- 9610889
TI  - Characterization of cementum derived growth factor as an insulin-like growth
      factor-I like molecule.
AB  - Cementum is the thin calcified outer layer through which tooth-root surfaces are
      anchored to soft periodontal connective tissues. A variety of growth factors and
      adhesion molecules are sequestered in the extracellular matrix of cementum, and
      we have purified and characterized one of the growth factors. This growth factor,
      the cementum derived growth factor (CGF), was purified from bovine cementum by
      acetic acid extraction followed by heparin affinity chromatography and HPLC using
      cation exchange, molecular sieve, and reverse-phase columns. NaDodSO4
      polyacrylamide gel electrophoresis of purified CGF preparation revealed the
      presence of two major protein bands migrating with Mr 18,000-22,000 and 14,000
      16,000. The latter was associated with the major part of the mitogenic activity.
      The activity of CGF was inhibited by antibodies to insulin-like growth factor-I
      (IGF-I) and IGF-I receptor. Both CGF and IGF-I were mitogenic to human gingival
      fibroblasts and alveolar bone cells, but the bone cells responded better to CGF
      than to IGF-I. The IGF-I did not bind to heparin-sepharose, while CGF bound to it
      and was eluted with 0.6M NaCl from heparin-sepharose columns. Heparin-sepharose
      0.2M NaCl fractions of cementum extracts contained IGF-I migrating with Mr 7,500,
      but its mobility was not affected by N-glycosidase treatment. Western analysis
      using anti-IGF-I antibodies showed that CGF preparations contained cross-reacting
      species migrating with Mr 18,000-22,000, 14,000-16,000 and 11,000-12,000, however
      after treatment with N-glycosidase the Mr 18,000-22,000 component was absent.
      Internal amino acid sequences of six tryptic peptides of CGF were determined by
      microsequencing. The sequence of one 15-amino acid long peptide was the same as
      the receptor binding domain of IGF-I, and another 9-amino acid peptide had 78 %
      homology to a sequence derived from an untranslated region of sheep IGF-I exon 1.
      Four other peptides had no apparent homology with IGF-I. From these results we
      conclude that the CGF is an IGF-I like molecule.

PMID- 9610890
TI  - ETS sites in the promoters of the matrix metalloproteinases collagenase (MMP-1)
      and stromelysin (MMP-3) are auxiliary elements that regulate basal and phorbol
      induced transcription.
AB  - The matrix metalloproteinases collagenase (MMP-1) and stromelysin (MMP-3) are
      often coordinately expressed, and their promoters contain similar regulatory
      elements, including an AP-1 site at about -70. There are, however, additional
      sequences including an adjacent ETS site at about -90 in both promoters, and a
      NIP (nuclear inhibitory protein) binding site in the stromelysin promoter. In
      this paper, we have investigated the role of these elements in transcriptional
      activation by phorbol myristate acetate (PMA). Using mobility shift assays, we
      demonstrate that in the collagenase promoter, PMA induction requires the binding
      of nuclear proteins to the ETS site as well as to the adjacent AP-1 element. In
      the stromelysin promoter, we used mutational analysis and DNA/protein
      interactions to illustrate a role for a single ETS site and for the NIP element
      in phorbol induction. These data suggest that ETS elements interact with other
      cis-acting sequences in these promoters to elicit transcriptional activation, and
      that the placement of the ETS sites in these promoters may influence
      transcriptional activity.

PMID- 9610891
TI  - Vascular endothelial growth pattern during demineralized bone matrix induced
      osteogenesis.
AB  - The purpose of the current study was to determine the timely ingrowth of blood
      vessels associated with demineralized bone matrix (DMB) induced osteogenesis.
      Critical-size (10 x 5mm), full thickness bony defects in rabbit parietal bone
      were implanted with DBM. Histological and ultrastructural changes were examined
      1, 2, 3, 4, 5, 6, 7 and 14 days later. Neovascularization was assessed by
      immunohistochemical staining for factor VIII antigen (marker for vascular
      endothelium) and also confirmed by staining using pan-endothelial antibody (CD31)
      (a marker for endothelium). Immunohistochemical evaluation revealed a positive
      staining for CD31 and Factor VIII expressed by endothelial cells by day 3 post
      grafting. By day 4, small blood vessels were first seen budding from host bed
      towards the grafted DBM. Ultrastructural identification of cells in the early
      stages of healing revealed the presence of macrophages. The monocyte-derived
      macrophage appears to play a central role in the repair process using DBM.
      Results of this study demonstrated a rapid vascularization during the DBM induced
      osteogenesis. This rapid vascularization is vital to the healing and bone
      induction ability of the DBM.

PMID- 9610892
TI  - A thermodynamic analysis of the contribution of hydroxyproline to the structural
      stability of the collagen triple helix.

PMID- 9610893
TI  - The Junior Radiology Forum: What do the trainees think about the future of
      oncology training?

PMID- 9610894
TI  - Cellular response to low-dose irradiation.

PMID- 9610895
TI  - Combined chemotherapy and radiation for locally advanced cervical carcinoma.

PMID- 9610896
TI  - The future of oncology training: from the trainees' perspective.
AB  - A fundamental step towards any potential integration of the specialties of
      medical and clinical oncology into a common faculty in the UK, is to establish a
      core curriculum of training in both cancer sciences and clinical cancer medicine
      for both specialties. A questionnaire was sent to all UK trainees in cancer
      medicine in March 1997 to establish a baseline of patterns of training and to
      gather information on the trainees' views regarding the future of oncology
      training. The results of this survey are presented along with suggestions for
      discussion on the future of oncology training.

PMID- 9610897
TI  - Life expectancy as a measurement of the benefit shown by clinical trials of
      treatment for early breast cancer.
AB  - Improvements in life expectancy could be a more readily appreciated measure of
      benefit from a clinical trial than relative risks, odds ratios or increases in
      survival rate at some arbitrary point in time. Parametric models of survival
      experience can be used to determine differences in life expectancy. Using the log
      normal model, it is shown that the increases in 10-year survival rate found by
      the overviews of adjuvant systemic therapy trials in early breast cancer are
      consistent with only small overall increases in life expectancy of about 1 year
      for Stage I and about 2 years for Stage II. However, if adjuvant therapy
      transfers a patient from being not cured to being cured, then her life expectancy
      will have been improved by 16 years for Stage I disease and by 21 years for Stage
      II. Model analyses on large data sets, such as are available in overviews, could
      possibly provide some evidence on whether the effect of adjuvant systemic therapy
      is to increase the cure rate, with the consequent considerable increase in life
      expectancy for some patients, or whether the effect is only a small increase in
      life expectancy for those who are not cured.

PMID- 9610898
TI  - A detailed baseline audit of radiotherapy for primary breast cancer: old habits,
      new principles.
AB  - In the UK, fundamental changes are occurring to the organization and delivery of
      services to breast cancer patients, prompted by the Calman/Hine initiative and by
      the perception that outcomes in the UK compare unfavourably with the rest of
      Europe and North America. Breast cancer, being a common malignancy, has often
      been treated by general surgeons and oncologists rather than by site-specialized
      multidisciplinary teams. Outcome results for many of these surgeons and
      oncologists may be unknown, so it becomes difficult, in any particular centre, to
      quantify changes that arise from the reorganization of treatment services and
      adherence to new guidelines without first determining baseline results. A
      retrospective audit of the 350 patients with primary breast cancer who received
      radiotherapy in Velindre NHS Trust in 1988-1989 has been performed to provide a
      baseline against which future results can be measured following the adoption of
      agreed guidelines. The endpoints for this study were: the completeness of data;
      actual treatment received versus current guideline recommendations; locoregional
      recurrence rates; and radiation related morbidity. The adherence to agreed
      guidelines is likely to ensure more appropriate surgery of the primary disease
      and will limit radiotherapy compared with 1988-1989 in that much radiation to the
      axilla and Internal Mammary Chain and 'booster' treatment to the primary site
      will be avoided in the future. The incidence of brachial plexus neuropathy was
      consistent with the radiation doses used and an analysis of this data suggests
      that the adoption of the guidelines will probably result in the complete
      avoidance of this complication in the future. Likewise, it is expected that the
      incidence of soft tissue fibrosis, telangiectasia and pneumonitis should
      diminish, but this and the effect of the clinical guidelines on local recurrence
      rates remains to be demonstrated by future comparable audits.

PMID- 9610899
TI  - The effectiveness of the routine clinic visit in the follow-up of breast cancer
      patients: analysis of a defined patient cohort.
AB  - The study aimed to identify the proportion of patients with relapse or a
      contralateral breast tumour who are diagnosed as a consequence of regular follow
      up in a specialist breast clinic after breast conserving surgery and radiotherapy
      for early breast cancer. A retrospective review was undertaken of 490 consecutive
      patients entered into a randomized clinical trial of radiotherapy fractionation
      at a single institution. As part of the trial, patients were reviewed in a
      multidisciplinary breast clinic 3-monthly for the first 3 years, 6-monthly
      between 3 and 5 years and annually thereafter, with biennial mammography. For
      this study, information was retrieved from hospital records to ascertain: (a)
      whether patients were symptomatic at the time of relapse or contralateral breast
      tumour; and (b) whether they presented at a scheduled appointment or brought
      their appointment dates forward. The subsequent management of patients with
      relapse was reviewed to determine whether or not this may have been influenced
      favourably by a policy of regular follow-up. Twenty-one (44%) of the 48 patients
      with locoregional relapse were asymptomatic. Of these, 17 were detected by
      clinical examination (that is, directly as a result of a routine clinic
      attendance), while four were detected by routine mammography. Ten of the 17
      patients diagnosed by clinical examination had successful surgery for
      locoregional relapse and all have remained disease free. Five of 17 developed
      distant metastases within 6 months and two others had skin nodules on the breast
      excised. Only three of the 67 patients with distant relapses were asymptomatic.
      Two of the 11 patients with contralateral breast tumours were asymptomatic and
      were diagnosed on routine mammography. The benefits and cost-effectiveness of
      less rigid approaches to follow-up of breast cancer patients needs to be
      evaluated in large prospective randomized trials.

PMID- 9610901
TI  - The history of radium in medicine in Manchester.

PMID- 9610900
TI  - Randomized multicentre trial of filgrastim as an adjunct to combination
      chemotherapy for Hodgkin's disease. West of Scotland Lymphoma Group.
AB  - This study was intended to ascertain whether the adjunctive administration of
      filgrastim (r metHuG-CSF, Amgen) would influence the dose intensity of
      chemotherapy or the morbidity of myelosuppression in patients receiving MOPP or
      MOPP/EVAP hybrid chemotherapy for Hodgkin's disease. In a prospective randomized
      trial, two regimens for the treatment of Hodgkin's disease were compared. The
      substudy described here randomized patients receiving either regimen to receive
      filgrastim on the days when chemotherapy was not administered. During
      chemotherapy, parameters of myelosuppression were documented, including dose
      delays, the severity and duration of neutrophil and platelet nadirs, infective
      episodes, and resulting hospital admissions. In the MOPP arm, 13/25 eligible
      patients, and, in the MOPP/EVAP arm, 12/22 eligible patients, received
      filgrastim. The use of filgrastim made no statistically significant difference to
      the administered dose intensity for either MOPP (P = 0.57, 95% confidence
      interval (CI) 15-point increase to 8-point reduction) or MOPP/EVAP (P = 0.53; 95%
      CI 7-point increase to 11-point reduction). In patients receiving MOPP,
      filgrastim reduced the median duration of leucopenia (P = 0.007) and the severity
      of the white blood cell nadir (P = 0.036); however, no statistically significant
      effect (at the 5% level) was seen in platelet or haemoglobin nadirs, the number
      of days of in-patient hospitalization, the number of admissions for infective
      complications, the incidence, grade or duration of infections, or the incidence
      of febrile neutropenia. In patients receiving MOPP/EVAP, filgrastim had no
      significant effect on the duration or depth of leucopenia but was associated with
      a reduction in the median haemoglobin (P = 0.002) and platelet nadirs (P =
      0.015). No effect on the above listed sequelae of myelosuppression was influenced
      by the administration of filgrastim. This study, although small, suggests that
      the routine use of filgrastim, aimed at influencing the administered dose
      intensity of conventional dose chemotherapy in Hodgkin's disease, is not
      warranted.

PMID- 9610902
TI  - Cervical spine involvement in metastatic colorectal carcinoma.
AB  - Bone metastasis in colorectal carcinoma is an uncommon occurrence. The lumbar and
      thoracic vertebrae are the most commonly reported sites. In contrast, the
      reported incidence of cervical vertebral involvement is relatively rare at 2%-7%.
      We document seven patients with colorectal carcinoma who presented with
      symptomatic cervical spine metastases and describe their clinical
      characteristics. This represents a disproportionately large number (24%) of those
      with bone metastases seen at this centre.

PMID- 9610903
TI  - Intralesional interferon for the treatment of metastatic carcinoid tumours.
AB  - We report the first documented case of intralesional interferon administration
      for the palliation of carcinoid tumour metastases. This was performed under
      ultrasound guidance and gave a good clinical response, which correlated with
      tumour necrosis demonstrated by serial CT scanning.

PMID- 9610904
TI  - Pitfalls of hCG monitoring in stage I seminoma.
AB  - We detail the case history of a patient with Stage I seminoma, who developed an
      elevated level of human chorionic gonadotrophin (hCG) while on follow-up. It
      transpired that the patient had injected himself with hCG several days before.
      This type of abuse has been documented, but this is the first reported case of it
      interfering with the follow-up of a patient with a germ cell tumour.

PMID- 9610905
TI  - Consensus conference on platelet transfusion. Royal College of Physicians of
      Edinburgh, UK.

PMID- 9610906
TI  - Fractionation or chemoradiation for head and neck cancer?

PMID- 9610907
TI  - The use of a cationic liposome formulation (DOTAP) mixed with a recombinant tumor
      associated antigen to induce immune responses and protective immunity in mice.
AB  - The cationic liposome DOTAP is a well-known transfection reagent. It has been
      manufactured and approved for clinical use, is readily available, and can be
      easily used as an adjuvant. These characteristics prompted us to investigate the
      effectiveness of DOTAP as an adjuvant to induce immune responses and protective
      immunity in mice using baculovirus-derived carcinoembryonic antigen (bV-CEA) as a
      model antigen. Two routes of administration and a dose-response study of bV-CEA
      were used in BALB/c mice to define the magnitude of the immune response as well
      as the most effective route of immunization. The results demonstrate differences
      in antibody titers, immunoglobulin (Ig)G isotype, and T-cell responses between
      the intravenous (i.v.) or subcutaneous (s.c.) route of immunization. The titer of
      the anti-CEA antibodies induced by the s.c. immunization was greater than the
      response by i.v. immunization. The s.c. route enhanced the IgG2a/2b isotype,
      whereas i.v. immunization elicited primarily IgG1. T-cell proliferation responses
      and cytokine production paralleled the humoral response (i.e., production was
      higher in the s.c. immunized animals). No differences in immunological responses
      were seen using either 25 or 10 microg of bV-CEA three times. An amount of 25
      microg of bV-CEA/DOTAP given by s.c. immunization was sufficient in protecting
      mice from the transplant of syngeneic tumor cells transduced with the human CEA
      gene. We conclude that the cationic liposome DOTAP may be a useful immunoadjuvant
      for active anti-tumor immunotherapy in future clinical trials. This study will
      help to define the most effective way to use such an adjuvant.

PMID- 9610908
TI  - Adenovirus-mediated interleukin-2 production by tumors induces growth of
      cytotoxic tumor-infiltrating lymphocytes against human renal cell carcinoma.
AB  - Combination therapy with interleukin-2 (IL-2) and tumor-infiltrating lymphocytes
      (TILs) demonstrates significant clinical activity in patients with metastatic
      renal cell carcinoma (RCC). To investigate whether local delivery of IL-2 via
      gene transfer is capable of improving the potency and efficacy of in vitro
      propagated TILs as compared with standard growth conditions [400 BRMP U (BU)/ml],
      a replication-deficient adenovirus expressing the human IL-2 gene under control
      of the cytomegalovirus (CMV) promoter (Ad-IL-2) has been constructed in our
      laboratory. RCC-TIL cultures were initiated by directly infecting RCC tumor
      suspension with Ad-IL-2 at a multiplicity of infection of 10:1. Subsequently the
      TIL cultures were restimulated with nonirradiated autologous RCC infected with Ad
      IL-2 (RCC-Ad-IL-2) every 10 days (TIL/tumor = 50:1). Cell growth, phenotype,
      cytotoxicity, and cytokine messenger RNA (mRNA) expression were analyzed and
      compared with TIL growth stimulated with exogenous IL-2 (400 BU/ml). All five
      TILs tested responded to RCC-Ad-IL-2 activation, and a completed clearance of
      tumor cells was observed in cultures within 7-10 days. Lysis of nonirradiated RCC
      Ad-IL-2 cells by TILs also was observed in cultures 3-5 days after restimulation.
      The IL-2 concentration in cell culture supernatants was maintained between 10 BU
      and 35 BU/ml (2 and 7 ng/ml), respectively. When compared with exogenous IL-2,
      RCC-Ad-IL-2 induced less growth expansion of TILs whereas a reduced CD56+ (23 +/-
      14% vs. 44 +/- 13%; p < 0.05) but increased CD3+CD4+ cell population (32 +/- 11%
      vs. 15 +/- 6%; p < 0.05) with enhanced T cell-receptor use (59 +/- 10% vs. 42 +/-
      7%; p < 0.005) was determined. An augmented human leukocyte antigen (HLA)
      restricted and tumor-specific cytotoxicity was detected in RCC-Ad-IL-2-expanded
      TILs (day 35, 15.3 +/- 4.2 LU vs. 4.6 +/- 1.8 LU; p < 0.005). These properties
      were mediated by the CD8+ and CD4+ T-cell populations, as demonstrated by
      antibody-blocking assays. A unique cytokine profile also was detected in RCC-Ad
      IL-2-induced TILs, which demonstrated an upregulation of both GM-CSF and IL-6
      mRNA as compared with TILs expanded in the presence of exogenous IL-2. These data
      suggest that RCC-Ad-IL-2 is a potent immune stimulant that can be used in vitro
      as an immunogen to propagate cytotoxic RCC-TILs for adoptive immunotherapy or
      potentially in vivo by direct injection as a live tumor vaccine.

PMID- 9610909
TI  - Regulation of T cell subsets from naive to memory.
AB  - To gain insights into the development and regulation of immune responses, we have
      studied the phenotype, cytokine profiles, activation requirements, and
      susceptibility to apoptosis of naive CD4, Th1, Th2 polarized effectors, resting
      memory, and memory effector cells. T cell receptor (TCR) transgenic mice were
      utilized as a source of enriched naive cells that could be used to generate
      effector and memory populations. The direct comparison of these populations,
      which all bear the same TCR, has revealed some interesting distinctions. When
      restimulated with antigen, effector populations secrete high titers of cytokines
      in polarized patterns. Retaining their polarized profile, memory cells secrete
      low levels and memory effector cells secrete very large levels of cytokine.
      Unlike naive CD4 T cells, effector cell proliferation is not dependent on classic
      co-stimulation but does require a threshold level of TCR signaling that can be
      enhanced by accessory interactions. Memory cells have intermediate requirements
      for co-stimulation/accessory interactions. However, different thresholds of
      activation are required for production of various cytokines, with requirements
      for production of interleukin (IL) 2 >> interferon-gamma > IL-4. CD4 subsets also
      differ dramatically in their susceptibility to apoptosis. Naive Th2 effectors and
      resting memory cells undergo activation-induced cell death (AICD) 4-7 days after
      antigen stimulation. In contrast, both primary and memory Th1 effectors undergo
      rapid AICD mediated by Fas/FasL within 0.5-2 days after stimulation. AICD is
      substantially blocked by IL-2 and transforming growth factor-beta1, resulting in
      impressive effector expansion. The process of memory development from effector
      populations remains mysterious, but these studies suggest roles for cytokines in
      promoting survival.

PMID- 9610910
TI  - Functional and molecular analysis of T cell receptors used by pancreatic- and
      breast tumor- (mucin-) specific cytotoxic T cells.
AB  - We have previously reported that tumor-specific cytotoxic T lymphocytes (CTLs)
      derived from pancreatic and breast cancer patients recognize specific epitopes on
      the mucin polypeptide core. These CTLs recognize breast and pancreatic tumor
      cells in a major histocompatibility complex (MHC)-unrestricted fashion, and the
      lytic activity of these T cells is mediated through the T cell receptor (TCR). To
      characterize the TCR-mediated MHC-unrestricted CTL function, we used
      semiquantitative polymerase chain reaction (PCR) and cytofluorometry to analyze
      the TCR repertoire in CTL lines established from cancer patients and specific for
      mucin-expressing tumors. We found three TCR Vbeta genes, Vbeta9, Vbeta13.1. and
      Vbeta17, predominantly expressed in these functional cell lines, established
      either from one patient by stimulation with various mucin-expressing targets or
      from different patients. Sequencing of these preferentially used TCR genes
      unveiled usage of distinct Jbeta and Cbeta but a potentially interesting
      conservation of certain amino acids in the CDR3 region.

PMID- 9610911
TI  - Intralesional selection of T cell clonotypes in the immune response to melanoma
      antigens occurring during vaccination.
AB  - T cells infiltrating pre- and postvaccine metastases obtained from melanoma
      patients vaccinated with either dinitrophenyl (DNP)-modified autologous tumor or
      with the MAGE-3.A1 peptide display selective T cell receptor (TCR) beta chain
      variable region (BV) repertoire changes at the tumor site as a consequence of
      vaccination. Restricted sets of BV families expand in all postvaccine lesions
      when compared with prevaccine specimens and often contain dominant clones. A
      protocol devised to obtain T cell lines highly enriched for expression of a given
      BV region through the use of anti-BV monoclonal antibodies was used to understand
      whether responses to specific antigen(s) accounted for these clonal expansions.
      In one of the patients vaccinated with DNP-modified tumor cells, BV-driven
      selection of the T lymphocytes expanded in two infiltrated postvaccine metastases
      resulted in T cell lines able to exert HLA class I-restricted lysis of the
      autologous tumor. These results indicate that TCR repertoire analysis at the
      tumor site facilitates the detection of T cell responses elicited by a vaccine
      and potentially cytotoxic for the autologous tumor.

PMID- 9610912
TI  - IL-3-mediated enhancement of particulate antigen presentation by macrophages.
AB  - Mice were exposed to interleukin- (IL-) 3 in vivo by injection of tumor cells
      transfected with the IL-3 gene. At 10 days post tumor injection, bone marrow
      cells were recovered, pulsed with particulate antigen in the form of ovalbumin
      (Ova)-coated magnetic beads, and tested for their ability to present antigen via
      class I to an Ova/class I-restricted T cell hybridoma. Cells from IL-3-stimulated
      mice exhibited a marked increase in antigen presentation compared with cells from
      mice injected with control non-cytokine-secreting tumor cells. These cells were
      markedly more efficient at presenting particulate Ova antigen than in presenting
      soluble Ova. Based on adherence, radiation resistance, and surface markers, the
      cells presenting antigen appear to be in the macrophage cell lineage. These cells
      are susceptible to lysis by antigen-specific cytotoxic T lymphocytes, which may
      contribute to limiting the effectiveness of antitumor responses.

PMID- 9610913
TI  - Cytokine gene therapy or infusion as treatment for solid human cancer.
AB  - In the induction of tissue-directed immune responses, cytokines tend to be
      released within the affected tissues. We used two strategies to expose tumor
      tissues to continuous high levels of cytokines: First, a vaccinia interleukin
      (IL)2 recombinant was injected directly intratumorally 3-weekly at 10(7)
      pfus/dose in six patients with the solid tumor malignant mesothelioma (MM). No
      virus excretion was detectable. At each cycle vaccinia-IL-2 mRNA (SQ [semi
      quantitative] reverse transcription polymerase chain reaction) was maximal 24-72
      h following injection reduced at 8 days and faded by 21 days. No tumor regression
      occurred. Second, based on the success of granulocyte macrophage colony
      stimulating factor (GM-CSF) in gene transfer experiments, we conducted a study
      using continuous intratumoral GM-CSF infusion in eight patients with MM using a
      portable pump at doses of 10 micro/cg/24 h over 8 weeks. Systemic neutrophil
      agglutination and local catheter-related difficulties occurred. Two patients
      demonstrated tumor necrosis, one of whom had a marked progressive mononuclear
      cell infiltration of the tumor associated with a partial response (>50% reduction
      in tumor area). Murine studies using our MM model in CBA and BALB/C mice have
      demonstrated that B7-1 and allo-class I transfections induce strong tumor
      specific cytotoxic T lymphocyte responses: GM-CSF, IL-12, and IL-2 induced mixed
      nonspecific plus specific responses, whereas B7-2 and class II transfections were
      not effective. We conclude that increased intratumoral cytokine concentrations
      can be generated using both gene transfer and cytokine infusion approaches;
      however, both have their limitations and, at this stage, have not produced
      dramatic antitumor effects in humans.

PMID- 9610914
TI  - Class II-transfected tumor cells directly present endogenous antigen to CD4+ T
      cells in vitro and are APCs for tumor-encoded antigens in vivo.
AB  - We have previously demonstrated that class II-transfected tumor cells are very
      effective immunogens that protect against wild-type primary and metastatic tumor
      and, if supertransfected with genes encoding co-stimulatory molecules, are
      immunotherapeutic agents that successfully treat mice with established solid
      tumor. These results are consistent with our hypothesis that the class II
      transfected tumor cells act as antigen-presenting cells (APCs) that directly
      activate tumor-specific CD4+ T cells; however, direct data supporting this
      hypothesis are lacking. In the present study, we test this hypothesis using class
      II-transfected tumor cells supertransfected with the hen egg lysozyme gene as a
      surrogate tumor antigen. In vitro antigen presentation assays demonstrate that
      class II-transfected tumor cells present to CD4+ T cells endogenously encoded
      tumor antigen, provided they do not co-express the class II-associated invariant
      chain. In vivo experiments using genetically marked tumor cells and host APCs
      demonstrate that both class II-transfected tumor cells and host cells are APCs
      for tumor-encoded antigens, although tumor cells appear to dominate the response.
      These results support the hypothesis that the immunogenicity and therapeutic
      value of class II-transfected tumor cells stem from their ability to function as
      APCs for tumor-encoded antigens and directly activate tumor-specific CD4+ T
      lymphocytes.

PMID- 9610915
TI  - CD40 and CD70 co-stimulate a potent in vivo antitumor T cell response.
AB  - In several studies, CD80, a potent co-stimulatory molecule, has been reported to
      be responsible for the induction of CD8+ antitumor T cell responses by CD80
      transfected tumor cells. However, expression of CD80 by tumors not always ensures
      generation of a T cell-mediated antitumor response. Variables such as the
      inherent immunogenicity of a tumor and its major histocompatibility complex (MHC)
      expression status affect the efficacy of this approach. Therefore, in this study
      two other co-stimulatory ligands, CD40 and CD70, have been investigated for their
      ability to co-stimulate antitumor responses. The efficacy of CD40 and CD70 is
      compared with that of CD80, with respect to CD4 and CD8 T cell co-stimulatory
      capacity in vitro and their ability to induce in vivo antitumor responses.
      Furthermore, CD40 and CD70 are tested for their capacity to induce a long-lived
      memory response in vivo, as defined both by induction of tumor-specific cytotoxic
      T lymphocytes (CTLs) and rejection of wild-type tumor cells. It was found that,
      despite the fact that CD40 predominantly stimulates CD4 T cells, CD40-transfected
      MHC class II-negative P815 tumor cells become highly immunogenic and induce long
      lasting memory tumor-specific CTLs in vivo. Furthermore, CD40 and CD70 emerge as
      powerful and even superior alternatives to CD80 for improving tumor
      immunogenicity in vivo. While the mechanisms by which they do so remain to be
      defined, these findings suggest additional strategies for immunotherapy.

PMID- 9610916
TI  - Opiate agonist-induced changes in behavioral sensitivity to clonidine are
      observed in perinatally malnourished rats exposed to chronic stress.
AB  - Sensitivity of alpha2-adrenoceptors following repeated immobilization sessions
      plus morphine (MOR) or beta-endorphin (BETA) was assayed by examining clonidine
      (CLO)-induced hypoactivity in adult malnourished rats at perinatal age. As
      previously described, chronic restraint did not attenuate the hypoactivity
      elicited by CLO in malnourished rats, although chronic restraint did have such an
      effect on motor activity in control animals. MOR and BETA administration prior to
      each restraint session induced subsensitivity of alpha2-adrenoceptors in
      malnourished rats as determined by a blunted response to clonidine challenge. An
      injection of naloxone (NAL) prior to BETA before each stress session fully
      antagonized the subsensitivity to clonidine observed in malnourished animals. A
      possible deficiency in the functional role of the opiate system in the process of
      adaptation to chronic stress in perinatal malnourished rats is suggested.

PMID- 9610917
TI  - Behavioral, electroencephalographic, and histopathologic effects of a
      neuropeptide isolated from Tityus serrulatus scorpion venom in rats.
AB  - The effects of intrahippocampal administration of a neuropeptide (TS-8F toxin)
      isolated from Tityus serrulatus scorpion venom have been determined on behavior,
      limbic seizures, and neuronal degeneration in rats. Behavioral observation showed
      orofacial automatism, wet dog shakes, and myoclonus. Concomitantly, the
      electroencephalographic record showed high-frequency and high-voltage spikes that
      evolved to seizure activity in the hippocampus and cortex. Seven days after TS-8F
      toxin microinjection, neuronal damage was observed in CA1 and CA2 pyramidal cells
      and in granular cells of the dentate gyrus. The results suggest that TS-8F toxin
      may be responsible, at least in part, by the epileptic effects observed with the
      crude venom. Thus, this toxin may be a useful tool in the study of some
      neurobiological process.

PMID- 9610918
TI  - Antagonism of ketamine-induced anesthesia by an inhibitor of nitric oxide
      synthesis: a pharmacokinetic explanation.
AB  - Because ketamine is an antagonist of NMDA receptors, and because some NMDA
      receptors activate nitric oxide synthesis in brain, this study examined if nitric
      oxide synthase (NOS) inhibition by L-NAME altered the course of ketamine-induced
      behavioral impairment. Rats given progressive doses of L-NAME until NOS activity
      was inhibited at least 90% displayed reduced depth and duration of behavioral
      depression after i.m. ketamine. Blood and brain concentrations of ketamine,
      norketamine, and its dehydrogenated derivative were isolated from rats previously
      given saline or L-NAME as above, by ether extraction, HPLC separation, and
      ultraviolet quantitation. The same doses of L-NAME that altered ketamine behavior
      reduced blood and brain ketamine concentrations 15 min after administration to
      about three-fourths and one-third of control, respectively. The content of
      norketamine and its adventitial extraction product were similarly reduced
      relative to control but the ratio of metabolites to ketamine was not
      significantly altered (p > 0.05) in brain. The decreased delivery of ketamine
      into brain, perhaps due to L-NAME-induced alterations in blood flow, may explain
      the reduced behavioral response to ketamine in these rats.

PMID- 9610919
TI  - Conditioned place preference induced by a combination of L-dopa and a COMT
      inhibitor, entacapone, in rats.
AB  - The interaction of dopamine (DA) precursor L-dopa and catechol-O
      methyltransferase (COMT) inhibitor, entacapone, was examined in rats using
      conditioned place preference (CPP) paradigm to assess reinforcement, and by
      measuring DA metabolism in the striatum and the limbic forebrain. Neither L-dopa
      (100 mg/kg i.p.) nor entacapone (30 mg/kg i.p.) alone induced CPP, but in
      combination they induced significant CPP. Entacapone alone had no effect on
      limbic or striatal DA concentrations, while it reduced the concentrations of the
      COMT products 3-methoxytyramine (3-MT), a metabolite reflecting DA release, and
      homovanillic acid (HVA) in both brain areas. L-dopa elevated limbic but not
      striatal 3-MT. L-dopa also slightly elevated limbic DA but had no effect on
      striatal DA concentration. L-Dopa-induced increase of 3-MT was attenuated by
      entacapone. Our results show for the first time that L-dopa is able to produce
      CPP in intact animals. This effect may be related to the findings that L-dopa
      increases synaptic DA concentrations in the limbic areas, and entacapone may
      enhance this elevation as it prevents the synaptic metabolism of DA.

PMID- 9610920
TI  - Modification of the anxiolytic action of 5-HT1A compounds by GABA-benzodiazepine
      agents in rats.
AB  - The general purpose of the present study was to analyze the possible interactions
      between the GABA benzodiazepine and the serotonin systems in the mediation of the
      antianxiety actions of 5-HT1A compounds. The anxiolytic effect of buspirone (5
      mg/kg), ipsapirone (5 mg/kg), indorenate (5 mg/kg), and 8-OH-DPAT (0.5 mg/kg) was
      established in the rat burying behavior test. Flumazenil (5 mg/kg), but not
      bicuculline (2.5 mg/kg), effectively counteracted the reduction in burying
      behavior produced by buspirone, ipsapirone, and 8-OH-DPAT. These same 5-HT1A
      compounds, at subthreshold doses, produced an important reduction in burying
      behavior when combined with diazepam (0.25 mg/kg). The effect of indorenate was
      not altered by any of the antagonists and, when combined with diazepam it
      produced large increases in burying behavior latency. Only buspirone alone and in
      combination with bicuculline or flumazenil impaired motor coordination as tested
      in the rota rod. Data are discussed on the bases of the interaction between the
      GABAergic and serotonergic systems, stressing species differences and variations
      due to the animal model of anxiety.

PMID- 9610921
TI  - Decreased activity of striatal monoamine oxidase B after rapid eye movement (REM)
      sleep deprivation in rats.
AB  - The striatum seems to be the main brain region involved in stereotyped behavior
      induced by dopaminergic agonists. Rapid eye movement (REM) sleep deprivation
      increases dopaminergic agonist-induced stereotypy and produces biochemical
      changes in striatal dopaminergic neurotransmission. However, the mechanism
      underlying the increased dopaminergic sensitivity induced by REM sleep
      deprivation has not been elucidated. In an attempt to determine some of the
      biochemical changes in striatal dopaminergic neurotransmission that could
      contribute to REM sleep deprivation effects, we measured the activity of
      monoamine oxidase (MAO) A and B, the enzymes responsible for dopamine and beta
      phenylethylamine (beta-PEA) deamination in striatum. Male adult rats were
      deprived of REM sleep for 96 h by the flower-pot technique. MAO A and B were
      assayed radioisotopically in the mitochondrial fraction by standard laboratory
      procedures, using [14C]-5-hydroxytryptamine (5-HT) and [14C]-beta
      phenylethylamine (beta-PEA), as substrates for MAO A and MAO B, respectively. The
      results showed no significant statistical differences in striatal MAO A activity,
      whereas a significant decrease in MAO B activity was observed. The results are
      discussed in terms of the possible involvement of beta-PEA, a striatal endogenous
      trace amine, which potentiates dopaminergic neurotransmission and may participate
      in the increased dopaminergic sensitivity observed after REM sleep deprivation.

PMID- 9610922
TI  - Pharmacological features of masculine sexual behavior in an animal model of
      depression.
AB  - Neonatal treatment with clomipramine induces behavioral alterations during
      adulthood that resemble symptoms observed in human depression. Therefore, it has
      been proposed as an animal model of depression. Impairment of male sexual
      performance is one of the main effects of this treatment. Using this model of
      depression, we evaluated the effects of drugs that stimulate sexual performance
      by acting selectively on the adrenergic, serotonergic, or cholinergic system.
      Yohimbine, a selective antagonist of the alpha-2 receptors; 8-OH-DPAT, a
      selective agonist of the 5-HT1A receptors; and oxotremorine, a muscarinic
      agonist, were administered to male rats neonatally treated with clomipramine that
      showed sexual behavior impairments. Yohimbine and oxotremorine induced only a
      slight improvement of sexual deficiencies. 8-OH-DPAT not only restored sexual
      behavior to normal levels, but induced facilitation in most of the copulatory
      parameters. These results suggest that neonatal treatment with clomipramine
      induces sexual deficits acting mainly on the adrenergic and cholinergic systems,
      while the serotoninergic system seems to be preserved.

PMID- 9610923
TI  - Relationships between midembryonic 5-HT2 agonist and/or antagonist exposure and
      detour learning by chickens.
AB  - The importance of serotonin (5-HT) as both a transmitter and a regulatory signal
      during development of many species is well established. The availability of 5-HT
      receptor subtype agonists and antagonists will enable pharmacological dissection
      of the importance of one or more of the 5-HT receptors for their involvement in
      the mediation of developmental insults by drugs that are less selective but
      include actions upon serotonergic function. Such insults include exposure to
      cocaine or opiate withdrawal, both of which are blocked or attenuated by 5-HT2
      antagonists. The 5-HT2 receptor agonist dimethoxyiodophenylaminopropane (DOI),
      like cocaine, causes vasoconstriction during embryogenesis, herniated umbilici in
      hatchlings, and altered detour learning by young chickens after injection into
      eggs at late stages of embryogenesis. The 5-HT2 antagonist ritanserin (RIT)
      blocks or significantly attenuates these effects. This study describes an effect
      of DOI on posthatch detour learning when injected earlier during embryogenesis
      (i.e., on embryonic day 12, E12) which is opposite its effect when injected later
      (i.e., on E15). Both effects are blocked by an inactive dose of RIT (0.3 mg/kg
      egg) and by a higher dose of RIT (0.9 mg/kg egg), which itself retards posthatch
      detour learning following E12 injection. Thus, excessive stimulation or blockade
      of 5-HT2 receptors around midembryogenesis can cause a similar behavioral
      teratogenic outcome. The data are discussed in relation to the likelihood that
      potential use of 5-HT2 antagonists for treating pregnant women and their fetuses
      who are not at risk is nil.

PMID- 9610924
TI  - A comparison of the effects of risperidone, raclopride, and ritanserin on
      intravenous self-administration of d-amphetamine.
AB  - These experiments were conducted to examine the effects of simultaneous blockade
      of dopamine D2 and 5-hydroxytryptamine2 (5-HT) receptor function on responding
      for intravenous infusions of d-amphetamine. Rats were trained to self-administer
      d-amphetamine intravenously according to a progressive ratio schedule of
      reinforcement, in which response requirements increased for successive infusions
      until responding extinguished. In the first experiment it was shown that
      increases in the unit infusion dose of d-amphetamine resulted in an increase in
      the number of amphetamine infusions earned. Thus, the strength of responding for
      d-amphetamine was linked to the dose of drug received. The mixed D2 and 5-HT2
      receptor antagonist risperidone (0.1, 0.2, and 0.4 mg/kg) reduced responding for
      d-amphetamine (60 microg/kg infusion). The selective D2 antagonist raclopride
      (0.1, 0.2, and 0.4 mg/kg) also reduced responding for d-amphetamine. In contrast,
      the selective 5-HT2 antagonist ritanserin (0.63, 1.25, and 2.5 mg/kg) failed to
      alter amphetamine self-administration. Combined injections of raclopride (0.05 or
      0.1 mg/kg) and ritanserin (2.5 mg/kg) were no more effective than injections of
      raclopride alone in reducing responding for d-amphetamine. Overall, these results
      suggest that 5-HT2 receptor blockade plays a negligible role in the rewarding
      effects of d-amphetamine measured by intravenous self-administration, and does
      not contribute to the suppressant effects of risperidone on this behavior.

PMID- 9610925
TI  - Discrimination of ethanol in rats: effects of nicotine, diazepam, CGP 40116, and
      1-(m-chlorophenyl)-biguanide.
AB  - The drug discrimination paradigm was used to evaluate the role of certain ligand
      gated ion channels in the discriminative stimulus properties of ethanol. Rats
      were trained to discriminate ethanol (1.0 g/kg) from saline vehicle under the
      FR10 schedule of sweetened milk reinforcement. The discrimination of lower
      ethanol doses was enhanced by either the GABA(A) receptor positive modulator,
      diazepam (0.5 mg/kg), or nicotinic acetylcholine receptor agonist, nicotine (0.3
      mg/kg). Neither diazepam nor nicotine produced any effect on the rate of
      responding. Both the NMDA receptor competitive antagonist, CGP 40116 (0.5 mg/kg)
      and the 5-HT) receptor agonist, 1-(m-chlorophenyl)-biguanide (5.0 mg/kg) enhanced
      the cueing properties of lower ethanol doses, but these effects were associated
      with a significant reduction in the response rate. The ethanol-like stimulus
      effects produced by diazepam or CGP 40116 were not influenced by 0.3 mg/kg
      nicotine. In contrast, CGP 40116 moderately enhanced the ethanol-like stimulus
      effects of diazepam. The present results show that: 1) pretreatment with
      nicotine, diazepam, CGP 40116 or 1-(m-chlorophenyl)-biguanide enhance the ethanol
      discrimination; 2) neither the GABA(A) nor the NMDA receptor complex alone is
      critically involved in the nicotine-induced enhancement of the ethanol
      discrimination; 3) NMDA receptor competitive antagonist and GABAergic
      benzodiazepine derivative may produce moderate additive effects in rats trained
      to discriminate ethanol.

PMID- 9610926
TI  - Cyclosporine A affects open field behavior in DA rats.
AB  - Since the introduction of Cyclosporine A (CsA) for immunosuppression in solid
      organ transplantation, the rate of allograft rejection has decreased
      substantially. However, treatment with CsA induces neuropsychological
      complications in patients, including affective disorders such as anxiety,
      disorientation, depression, aggression, paranoia, and apathy. These CsA-induced
      affective side effects cannot be extensively studied in humans. Therefore, this
      study investigates the effects of intraperitoneal CsA (20 mg/kg) injections on
      the open-field behavior of male Dark Agouti (DA) rats 1, 6, 12, and 23 h after
      drug administration on 3 consecutive days. CsA induced an increase in
      emotionality in DA rats 6 h after injection, reflected by decreased ambulatory
      activity in the open field and increased defecation. In addition, a decrease in
      rearing activity was observed 12 h after CsA administration. These behavioral
      alterations are discussed in the view of changes in cytokine profiles induced by
      CsA.

PMID- 9610927
TI  - The effects of branched chain amino acid infusion on pain perception and plasma
      concentrations of monoamines.
AB  - Infusions of branched chain amino acids (BCAA) have been shown to have several
      CNS-mediated effects including antinociceptive action. We investigated the
      effects of BCAA infusion on pain perception, respiratory control, and plasma
      monoamine concentrations. Six healthy female volunteers were given in a double
      blind, random, crossover design an 8-h infusion (1.75 ml/kg/h) of either (a)
      Ringers lactate, (b) conventional 4% amino acid solution, or (c) 4% BCAA solution
      with intervals of at least 48 h. Respiratory control was evaluated with
      continuous capnography. Pain perception was measured using dental dolorimetry for
      sharp pain, and pain transmitted by afferent C-fibers was evaluated with
      tourniquet test. Changes in vigilance were measured using critical flicker fusion
      technique. Evaluations were made for baseline, and after 2.5, 5, and 8 h. Plasma
      samples were collected at the same time points for amino acid and monoamine
      analysis. BCAA infusion resulted in significant increases of plasma
      concentrations of all BCAAs, with a simultaneous decrease in concentrations of
      aromatic amino acids. Of the measured monoamines and their metabolites
      dihydroxyphenylacetic acid (DOPAC) decreased, showing significant treatment
      effect for BCAA. Despite these changes no significant effect of BCAAs on
      respiratory control, vigilance, or pain perception was observed. In conclusion,
      despite significant changes in plasma concentrations of both amino acids and
      DOPAC, BCAA infusion did not show any clinically relevant antinociceptive effect.

PMID- 9610928
TI  - Cocaine and selective monoamine uptake blockers (sertraline, nisoxetine, and GBR
      12935) prevent the d-fenfluramine-induced head-twitch response in mice.
AB  - Serotonin release subsequent to 5-HT precursor loading mainly occurs via
      exocytosis. Acute cocaine or sertraline administration promote the ability of 5
      HT precursors (e.g. L-tryptophan) to induce the 5-HT2A receptor-mediated head
      twitch response (HTR) in rodents. The 5-HT releaser, d-fenfluramine, at
      behaviorally active doses, can induce the head-twitch response in rodents by
      releasing cytoplasmic 5-HT via the serotonin uptake carrier working in reverse.
      The purpose of the present study was to utilize the d-fenfluramine-induced HTR to
      determine the serotonergic and nonserotonergic components of cocaine's actions on
      the d-fenfluramine-sensitive pool of cytoplasmic 5-HT. Because a dramatic
      differential potentiation in HTR frequency is obtained when cocaine is
      administered prior relative to after L-tryptophan injection, the effects of
      varying doses of cocaine and the selective serotonin (sertraline), dopamine (DA)
      (GBR 12935), and norepinephrine (NE) (nisoxetine) uptake blockers were
      investigated on the d-fenfluramine-induced behavior in two experimental
      protocols. Thus, each uptake inhibitor was administered either 10 min following
      (protocol 1) or 10 min prior to (protocol 2) d-fenfluramine injection. All the
      tested uptake inhibitors attenuated the d-fenfluramine-induced HTR in a dose
      dependent manner in both experimental protocols. However, their order of potency
      in either protocol 1 (nisoxetine > GBR 12935 > cocaine > sertraline) or protocol
      2 (cocaine > GBR 12935 > nisoxetine = sertraline) does not agree with in vitro
      affinity of these drugs for the 5-HT transporter. In addition, the potency order
      for cocaine and nisoxetine in protocol 1 was significantly reversed in protocol
      2. The inhibitory effects of the cited drugs on the d-fenfluramine-induced HTR
      are discussed in terms of: 1) high doses of selective monoamine uptake blockers
      may not exhibit as much selectivity for their target uptake sites as indicated by
      in vitro tests; and 2) possible pharmacokinetic interactions between d
      fenfluramine and the monoamine uptake blockers.

PMID- 9610929
TI  - N(G)-nitro-L-arginine methyl ester reduces stress-related feeding in the rat tail
      pinch model.
AB  - A possible role of nitric oxide (NO) in stress-related feeding was investigated
      in male rats using the tail-pinch (TP) model, in within-subjects experimental
      designs. An initial experiment demonstrated a dose-related reduction in TP
      induced solid food intake over a 10-min test period with increasing dose (10.25,
      and 50 mg/kg SC) of the NO-synthase (NOS) inhibitor, N(G)-nitro-L-arginine methyl
      ester (L-NAME), reaching statistical significance at 25 mg/kg L-NAME when
      compared to vehicle control (p < 0.05). Pattern analysis further revealed a
      decrease both in total duration of food-directed oral behavior and in percentage
      of longer duration (> 60 s) oral behavior bouts with increasing dose of L-NAME;
      both measures reached statistical significance at 50 mg/kg (p < 0.01).
      Pretreatment with 500 mg/kg of the NO precursor, L-arginine (L-arg), resulted in
      partial but not significant reversal of the attenuating effect of 25 mg/kg L-NAME
      on food intake. Latency to begin eating or gnawing was not significantly affected
      by L-NAME. In a subsequent experiment, L-arg alone (500 and 750 mg/kg) did not
      significantly alter TP-induced food intake. It is cautiously suggested that these
      results implicate involvement of NO in TP-induced feeding.

PMID- 9610930
TI  - Neonatal withdrawal following pre- and postnatal exposure to methadone in the
      rat.
AB  - Recent evidence has shown that infant rats undergo precipitated withdrawal
      following chronic postnatal injection of morphine. In this study we examined
      whether or not infants exposed to methadone prenatally via the placental blood
      supply and postnatally via the dam's milk would also experience precipitated
      withdrawal. Dam's were implanted on gestational day 14 with osmotic minipumps
      containing one of two concentrations of methadone to supply the opiate throughout
      gestation and the first postnatal week. Nontreated and pair-fed controls were
      used. On postnatal day 7, pups were injected with naltrexone and their locomotor
      activity and ultrasonic vocalizations measured. Methadone exposed pups were more
      active and vocalized more when injected with naltrexone than with saline. The
      controls did not show these behavioral changes. The milk of methadone-exposed
      dams apparently contains sufficient quantities of the opiate for dependence to
      develop. The results are consistent with other data that demonstrate that very
      young rat pups can experience an opiate abstinence syndrome that includes
      increased behavioral activation.

PMID- 9610931
TI  - Chronic d-fenfluramine treatment reduces fat intake independent of macronutrient
      preference.
AB  - We investigated the effect of chronic dexfenfluramine (DFEN) treatment on
      macronutrient selection in a three-choice diet paradigm using Sprague-Dawley
      rats. Baseline macronutrient intakes were measured for several days before the
      initiation of treatment. In Experiment 1, daily intraperitoneal injections of
      DFEN (1.5 mg/kg) or saline were administered 60 min before dark onset for 12
      consecutive days and 24 h macronutrient intakes were measured. DFEN significantly
      reduced absolute fat intake (kcal) by 30% and relative fat intake (% of total
      energy) by 14% in animals that received dexfenfluramine treatment compared to
      controls over the 12-day period. Absolute carbohydrate intake was increased 24%
      compared to controls, but this difference was not significant. These changes in
      food intake resulted in a 10% lower total energy intake. Upon discontinuation of
      the drug, fat intake of the DFEN-treated rats rebounded to control levels within
      24 h. In Experiment 2, rats were assigned to carbohydrate- or fat-preferring
      groups based on the ratio of their average daily carbohydrate to fat intake
      (kcal). All animals then received DFEN. During DFEN treatment, fat-preferring
      rats reduced their daily fat intake from 62 to 53% of total energy. The low
      baseline fat intake of carbohydrate-preferring rats was reduced even further by
      DFEN (from 24 to 15% of total energy). These corresponding effects of DFEN on
      macronutrient selection in both fat- and carbohydrate-preferring rats indicate
      that chronic DFEN treatment selectively suppressed fat intake independent of the
      preferred macronutrient diet.

PMID- 9610932
TI  - Olfactory cues and morphine-induced conditioned analgesia in rats.
AB  - In a Pavlovian conditioning procedure, rats were exposed to an odor conditioned
      stimulus (CS) and then were given morphine with its effect serving as the
      unconditioned stimulus (US). After four CS-US pairings, the CS was tested alone
      to assess the presence of an analgesic conditioned response (CR) using a hot
      plate test. In Experiment 1a, two groups were conditioned by pairing either 10
      mg/kg morphine or saline with an odor CS. In Experiment 1b, two groups were given
      an odor CS paired or unpaired with 10 mg/kg morphine. These results established
      that an odor cue can support a morphine-induced analgesic CR. Experiment 2
      characterized the dose-effect curve (0, 3, 10, and 30 mg/kg morphine) using an
      odor conditioning procedure. The dose-effect curve showed an inverted U-shaped
      function, with the 10 mg/kg morphine group having significantly longer paw-lick
      latencies compared to all other groups. This finding contrasts with the
      monotonically ascending dose-effect curve for the analgesic unconditioned
      response (UR) to morphine.

PMID- 9610933
TI  - The putative AMPA receptor antagonist, LY326325, produces anxiolytic-like effects
      without altering locomotor activity in rats.
AB  - Anxiolytic-like effects produced by the novel, water-soluble AMPA/kainate
      receptor antagonist, LY326325 (3RS,4aRS,6RS,8aRS)-6-[2-(1(2)H-tetrazole-5-yl)e
      thyl]decahydro-isoquinoline-3-carboxylic acid), were examined in the elevated
      plus-maze and in a conflict-suppressed drinking situation. Administration of low
      doses (0.5, 1.2, and 5 mg/kg; i.p., -30 min) of LY326325 to Sprague-Dawley rats
      did not alter the percentage of entries into the open arms of the plus-maze,
      whereas only one dose of LY326325 (1 mg/kg) produced a slight, but significant,
      increase of the time spent in the open arms of the plus maze. In the conflict
      suppressed drinking test, similar doses of LY326325 (2.5 and 5 mg/kg; i.p., -30
      min) caused a dose-dependent and significant increase of punished drinking
      behavior without having any significant effects on unpunished drinking. The
      anxiolytic-like effects of LY326325 in the plus-maze and in the anticonflict
      tests were observed at doses, which, by themselves, had no influence on various
      measures of locomotor activity, i.e., horizontal activity, forward locomotion,
      and corner time. Our data suggest that the putative AMPA/glutamate receptor
      antagonist, LY326325, produces anxiolytic-like effects similar to those of
      diazepam in the conflict-suppressed drinking test, but displays considerably
      weaker anxiety-reducing properties compared to diazepam in the elevated plus
      maze.

PMID- 9610934
TI  - Antineophobic effect of the neuroactive steroid 3alpha-hydroxy-5beta-pregnan-20
      one in male rats.
AB  - The neuroactive steroid 3alpha-hydroxy-5beta-pregnan-20-one (pregnanolone) and
      benzodiazepine receptor (BZR) agonists share sedative, anxiolytic, and
      anticonvulsant properties. Recent evidence suggests that like BZR agonists,
      pregnanolone may also modulate feeding responses. The present experiments
      examined the behavioral mechanisms responsible for any hyperphagic effect of
      pregnanolone. The effect of pregnanolone (1-10 mg/kg i.p.) on the intake and
      microstructure of licking for two sucrose solutions (1 and 3%) in well
      familiarized nondeprived male rats under either light or dark conditions was
      examined. Pregnanolone had no effect on either intake or the duration or number
      of bouts of licking in these experiments, although in all cases the intrabout
      lick rate was significantly reduced at the highest dose. Pregnanolone (1-10
      mg/kg) also failed to increase intake of a sweet wet mash in familiarized
      nondeprived male rats. However, in a food choice test where both novel and
      familiar food items were available, pregnanolone (1-3 mg/kg) significantly
      increased the time spent eating the novel food. These results suggest that unlike
      BZR agonists, which enhance feeding responses directly, pregnanolone may
      facilitate feeding secondarily via an attenuation of anxiety.

PMID- 9610935
TI  - Antipsychotic-like profile of alstonine.
AB  - Although recently developed drugs have brought significant improvement, the
      treatment of psychotic disorders still presents serious drawbacks. Because
      inherent complexity and lack of satisfactory understanding of the underlying
      pathophysiology impose limits for rational drug design, resourceful approaches in
      the search for antipsychotics are pertinent. This article reports pharmacological
      properties of alstonine, a heteroyohimbine-type alkaloid, which exhibited an
      antipsychotic-like profile, inhibiting amphetamine-induced lethality, apomorphine
      induced stereotypy, and potentiating barbiturate-induced sleeping time. Atypical
      features of alstonine were the prevention of haloperidol-induced catalepsy and
      lack of direct interaction with D1, D2 and 5-HT2A receptors, classically linked
      to antipsychotic mechanism of action.

PMID- 9610936
TI  - 8-OH-DPAT interacts with sexual experience and testosterone to affect ejaculatory
      response in rats.
AB  - Studies investigating the effect of 8-OH-DPAT (DPAT) on male sexual response have
      typically used subjects having variable sexual experience and levels of
      testosterone, factors known to independently influence male sexual behavior. This
      experiment examined the role of these two variables in the mediation of DPAT
      effects on sexual behavior. One hundred and six castrated males, half of whom
      received sexual experience, were tested with an effective dose of 8-OH-DPAT (0.1
      mg/kg) or saline. In addition, males were tested under one of three regimens of
      testosterone. Results indicated that DPAT and testosterone exerted independent
      effects on ejaculatory measures, and along with sexual experience, showed
      interactive effects as well. When testosterone (T) levels were substantially
      below normal, DPAT showed no effect. When T reached threshold levels, the DPAT
      effect was limited to sexually experienced males. At high T levels, both
      experienced and naive males exhibited strong effects from DPAT. In contrast with
      ejaculatory measures, mounting and intromitting behaviors were relatively
      unaffected by DPAT. These results emphasize the importance of specifying both the
      animal's sexual history and its testosterone profile in studies investigating
      pharmacological effects on sexual response.

PMID- 9610937
TI  - Nijmegen high and low responders to novelty: a new tool in the search after the
      neurobiology of drug abuse liability.
AB  - Knowledge about the differences in structure, function, and reactivity of the
      brain and body between Nijmegen high responders to novelty and Nijmegen low
      responders to novelty may help us to understand which factors give rise to the
      vulnerability and/or susceptibility to drugs of abuse. For that purpose, this
      contribution provides a short overview of the outcome of the available studies on
      Nijmegen high responders to novelty and Nijmegen low responders to novelty. These
      animals can be selected using three major behavioral paradigms: (a) the open
      field test (which allows the separation of high and low responders to novelty);
      (n) the intruder test (which allows the separation of fleeing and nonfleeing
      rats); (c) the apomorphine test (which allows the separation of apomorphine
      susceptible and apomorphine-unsusceptible rats). Data to date suggest that the
      same traits have been selected by all three paradigms, and point to the
      hypothesis that the neurochemical state of the nucleus accumbens directs the
      sensitivity to drugs of abuse. In addition, recent evidence suggests that the
      sensitivity to the psychostimulant and/or reinforcing effects of dexamphetamine
      and ethanol is smaller in HR than in LR under certain experimental conditions,
      whereas the reverse is found when different experimental conditions are chosen.
      The data all together lay the foundation for the overall hypothesis that there
      are three factors ultimately determining the individual-specific sensitivity to
      drug of abuse: (a) the genetic background that predisposes an individual to
      become a HR or a LR, (b) early postnatal factors that direct the phenotypic
      expression of a particular genotype at adult age, and (c) the degree of stress
      during exposure to the drug of abuse. Further testing of this hypothesis may
      provide important information about the factors that contribute to individual
      differences in vulnerability to drugs of abuse.

PMID- 9610938
TI  - Effects of the experimental diabetes on dopamine D1 receptor-mediated locomotor
      enhancing activity in mice.
AB  - The effects of diabetes on the dopamine-related locomotor-enhancing activities
      were studied in mice. Although spontaneous locomotor activity in diabetic mice
      was significantly greater than that in nondiabetic mice, the locomotor-enhancing
      effects of methamphetamine (4 mg/kg, s.c.), cocaine (20 mg/kg, s.c.) and SKF82958
      (1 mg/kg, s.c.), a selective dopamine D1-receptor agonist, in diabetic mice were
      significantly lower than those in nondiabetic mice. When dopamine level in the
      whole brain was reduced by pretreatment with 6-hydroxydopamine (6-OHDA),
      spontaneous locomotor activity was significantly reduced in both nondiabetic and
      diabetic mice. There was no significant difference in the total spontaneous
      locomotor activity counts within 3 h between 6-OHDA-treated nondiabetic and 6
      OHDA-treated diabetic mice. Furthermore, the locomotor-enhancing effect of
      SKF82958 in 6-OHDA-treated diabetic mice was also significantly lower than that
      in 6-OHDA-treated nondiabetic mice. In a binding assay, the Bmax values of
      [3H]SCH23390 binding to whole-brain membranes of diabetic mice were significantly
      lower than those in nondiabetic mice. However, there was no significant
      difference in the Kd values between nondiabetic and diabetic mice. These results
      suggest that the decreased density of dopamine D1 receptors in diabetic mice may
      result in hyporesponsiveness to dopamine-related locomotor enhancement.

PMID- 9610939
TI  - Emergence of oral and locomotor activity in chronic haloperidol-treated rats
      following cortical N-methyl-D-aspartate stimulation.
AB  - Neuroleptic-induced orofacial movements in rats have been widely utilized as an
      animal model of tardive dyskinesia (TD). The present study investigated the role
      of the oral motor cortex in these movements by applying direct cortical
      stimulation in rats exposed to chronic haloperidol. Rats received depot i.m.
      injections of haloperidol decanoate or sesame oil vehicle every 3 weeks (10 rats
      per group). After 24 weeks of injections and a 3-week withdrawal period,
      bilateral guide cannulae were implanted into the primary oral motor cortex. After
      a 1-week recovery, bilateral microinfusions of saline vehicle followed by 1, 3,
      and 10 mM N-methyl-D-aspartate (NMDA) were given and observations of oral
      activity, locomotion, rearing, and grooming were recorded. Haloperidol-treated
      rats displayed a significant emergence of NMDA stimulated oral activity
      (nondirected oral movements, oral tremor, audible teeth grinding, and directed
      oral movements). In addition, rearing and locomotion were significantly elevated
      in these animals. In contrast to haloperidol-treated rats, sesame oil-treated
      rats showed no significant emergence of any motor activity. These results suggest
      that chronic haloperidol administration alters primary motor cortex efferents,
      and that this effect may be a factor in the manifestation of chronic neuroleptic
      induced motor side effects, such as TD.

PMID- 9610940
TI  - Behavioral and neuroendocrine assessment of ritanserin exposure in the developing
      chicken: lack of toxicity at effective doses.
AB  - The 5-HT2 antagonist ritanserin (RIT) is undergoing Phase III clinical trials for
      the treatment of substance abuse disorders. RIT has also shown preclinical
      therapeutic potential for attenuating or blocking lethal and/or toxic effects of
      exposure to cocaine or the selective 5-HT2 agonist dimethoxyiodophenyl
      aminopropane (DOI) in the developing chicken. To assess the potential toxicity
      ("side effects") of RIT itself during development, we exposed chicken embryos to
      0, 0.1, 0.3, 0.9, or 2.7 mg RIT/kg egg by injecting the drug into eggs with 14
      day-old embryos (E14). Voltage generated by spontaneous embryonic activity
      (motility) was measured on E15 to assess short-term effects of RIT; none were
      observed. There was no overall effect of these RIT doses on hatchability, though
      sample sizes were small (n = 13-15 per group). One to 2 weeks after hatching,
      chicks' acquisition of a detour learning response was tested. There were no
      observable effects of any RIT dose on detour learning. To assess potential
      effects of RIT on responsiveness to stress, some chicks were exposed to isolation
      stress approximately 3 weeks after hatching and killed 15 min later. Blood was
      assayed for serum corticosterone. There was no effect of any embryonic RIT dose
      on corticosterone concentrations in nonstressed subjects. Although corticosterone
      was elevated in all stressed groups, the group exposed to the highest embryonic
      RIT dose (2.7 mg/kg egg) showed a stress-induced elevation greater than other
      groups. Thus, except for the highest RIT dose (six to seven times greater than a
      therapeutically effective dose used in earlier work), embryonic RIT exposure on
      E14 had no effect on embryonic behavior, hatchability, posthatch learned
      behavior, and basal serum corticosterone concentrations. At a supraefficacious
      dose it appears to have modified the responsiveness of the neuroendocrine axis to
      mild stress.

PMID- 9610941
TI  - Characterization of delta9-tetrahydrocannabinol and anandamide antinociception in
      nonarthritic and arthritic rats.
AB  - Little is known about the effectiveness of delta9-tetrahydrocannabinol (THC) and
      anandamide in blocking mechanical nociception. Even less is known about their
      antinociceptive efficacy in chronic inflammatory arthritis induced by Freund's
      complete adjuvant. The hypothesis was tested that THC and anandamide elicit
      antinociception in the paw pressure test, and that arthritic rats would exhibit a
      different response. In nonarthritic rats, THC- and anandamide-induced
      antinociception lasted 90 min and 15 min, respectively, while antinociception
      lasted 90 min and 30 min, respectively, in arthritic rats. Area under the curve
      calculations revealed no effect of arthritis on THC- and anandamide-induced
      antinociception. Another hypothesis was that paw pressure thresholds in arthritic
      rats reflect chronic cannabinoid receptor stimulation due to elevations in free
      anandamide levels. Yet, the CB1 receptor antagonist SR141716A failed to alter paw
      pressure thresholds in either nonarthritic or arthritic rats. Further
      investigation revealed that SR141716A significantly blocked THC antinociception,
      with no effect on anandamide. Thus, anandamide's effects did not result from CB1
      receptor stimulation, and any potential contribution of endogenous anandamide in
      arthritis was not revealed. Finally, THC and anandamide appear to release an as
      yet unknown endogenous opioid, because naloxone significantly blocked their
      effects. This study indicates that anandamide and THC may act at different
      receptor sites to modulate endogenous opioid levels in mechanical nociception.

PMID- 9610942
TI  - The abuse potential of zolpidem administered alone and with alcohol.
AB  - The abuse potential of zolpidem, alone and in combination with alcohol, was
      examined in healthy volunteers with a history of social use of alcohol and drugs.
      Zolpidem, a short-acting imidazopyridine hypnotic with selectivity for a
      benzodiazepine receptor subtype (BZ1 or omega1), was administered double blind at
      0, 10, or 15 mg with alcohol (0.75 g ethanol/kg b.wt.) or with placebo beverage
      in a randomized, six-way crossover design. Outcome measures included the Drug
      Effect Questionnaire (DEQ), the Addiction Research Center Inventory (ARCI-40),
      and the Profile of Mood States (POMS). Blood alcohol concentrations (BACs) were
      not significantly modified by zolpidem. Relative to placebo, zolpidem and alcohol
      significantly (p < 0.05) increased drug strength perception, drug-liking, and
      drug-disliking scores on the DEQ. On the ARCI-40, zolpidem and alcohol
      significantly increased sedation/intoxication and dysphoria/fear scores, but did
      not significantly change euphoria/well-being scores. Zolpidem and alcohol were
      rated more unfavorably than placebo on the POMS. Alcohol did not have additive
      effects on the subjective ratings for zolpidem. It is concluded that, for this
      population and at the doses tested, the abuse potential of zolpidem appears to be
      modest and not increased by alcohol.

PMID- 9610943
TI  - Perinatal treatment with picrotoxin induces sexual, behavioral, and
      neuroendocrine changes in male rats.
AB  - The effects of maternal exposure to picrotoxin (PT) during the prenatal and
      postnatal periods of sexual brain differentiation were studied. Behavioral
      (sexual behavior), physical (sexual maturation, body, and organ weights) and
      neurochemical (striatal and hypothalamic monoamine and respective metabolite
      levels) data were assessed in the offspring of PT-treated dams. The following
      results were obtained: 1) sexual maturation as measured by the day of testis
      descent and testis weight comparison was unchanged; 2) a decrease in male sexual
      behavior occurred, as well as a decrease in body, ductus deferens, and seminal
      vesicle weights and in plasma testosterone levels of adult male offspring; 3)
      striatal dopamine (DA) and homovanillic acid (HVA) levels were decreased and
      hypothalamic norepinephrine (NE) levels were increased. These results indicate
      that perinatal exposure to PT during the critical periods of male brain sexual
      differentiation has long-term effects on the reproductive physiology and behavior
      of male rats.

PMID- 9610944
TI  - Corticotropin-releasing factor and defensive withdrawal: inhibition of monoamine
      oxidase prevents habituation to chronic stress.
AB  - There is growing evidence for a role of extrahypothalamic corticotropin-releasing
      factor (CRF) in the pathogenesis of anxiety. A modified form of the defensive
      withdrawal test was used to test the anxiogenic effects of acute administration
      of intracerebroventricular (1 microg, i.c.v.) CRF in adult male rats. Habituation
      to the mild stress of daily handling and subcutaneous (s.c.) saline injection
      over 2-6 weeks abolished the anxiogenic effects of exogenous CRF. At 6 weeks this
      habituation also resulted in attenuation of baseline withdrawal behavior. CRF
      receptor binding was significantly decreased in the amygdala of chronically
      handled animals and may have been responsible for this habituation phenomenon.
      Comparison of rats treated with the monoamine oxidase (MAO) inhibitor, phenelzine
      [3 mg/kg, s.c., daily for 2-6 weeks] to the saline-treated groups revealed a
      failure to habituate to the chronic handling, as the baseline withdrawal (after
      injection of artificial CSF) by the phenelzine-treated animals was not different
      from the baseline withdrawal by unhandled rats. In comparison to rats treated
      chronically with saline, phenelzine treatment enhanced the anxiogenic effect of
      CRF. In summary, habituation to a mild chronic stress decreased baseline
      defensive withdrawal. Intraventricular administration of CRF produced an
      anxiogenic response as measured in the defensive withdrawal test, which was lost
      through exposure to mild chronic stress. Two or 6 weeks of daily handling and SC
      saline injection caused a downregulation of CRF receptors in the amygdala, which
      could account for the behavioral habituation and the loss of CRF-induced
      defensive withdrawal. Phenelzine treatment concurrent with mild chronic stress
      prevented habituation and maintained the anxiogenic effect of CRF in spite of the
      downregulation of CRF receptors in the amygdala.

PMID- 9610945
TI  - Morphine-induced conditioned place preference in preweanling and adult rats.
AB  - The ability of morphine to support a conditioned place preference (CPP) in
      preweanling (18-22-day-old) and adult (70-90-day-old) rats was assessed. Prior to
      a 15-min compartment preference test, subjects received a saline-paired, 30-min
      exposure to a distinct compartment 2 h prior to receiving an injection of 1 or 5
      mg/kg of morphine or saline, paired with a 30-min exposure to an alternate
      compartment for 4 consecutive days. Although overall activity levels differed
      substantially across age, preweanling and adult rats displayed similar patterns
      of activity during conditioning. Moreover, only adults exhibited a significant
      sex difference; females were more active than were males following an injection
      of 5 mg/kg of morphine. Both doses of morphine supported a comparable CPP in
      preweanlings and adults, and both ages exhibited relatively low activity levels
      while in the morphine-paired compartment. These similarities across age suggest
      that the CPP procedure may prove to be useful in elucidating the ontogeny of
      learning, memory, and stimulus selection in rats.

PMID- 9610946
TI  - Ring A reductions of progestins are not essential for estrous behavior
      facilitation in estrogen-primed rats.
AB  - In Experiment 1 six dose levels (range 0.66-2000 microg) of progesterone (P) and
      two synthetic progestins with a double bond at C6: megestrol acetate (MA) and
      chlormadinone acetate (CA), which cannot be reduced at C5, were injected to
      estrogen-primed (2 microg estradiol benzoate 42 h earlier) ovariectomized (ovx)
      rats. The three progestins elicited significant lordosis and proceptive
      behaviors. Potency analysis showed that MA was the most potent progestin for
      stimulating estrous behavior, followed by P and CA. These results suggest that
      ring A reduction of progestins to 5alpha/5beta metabolites is not essential for
      the facilitation of estrous behavior in ovx estrogen-primed rats. Progestins with
      the 3-ketone group and a double bond at C4 can also be reduced at C3 to yield
      3alpha-hydroxysteroid metabolites potentially capable of stimulating estrous
      behavior. In Experiment 2, the relevance of the formation of 3alpha
      hydroxysteroid metabolites for estrous behavior facilitation was tested by
      concurrently injecting indomethacin (1.5 mg), a blocker of 3alpha-hydroxysteroid
      oxidoreductase, with 400 microg of P, MA, or CA to ovx estrogen-primed rats.
      Indomethacin failed to block the stimulatory effect of these progestins on
      estrous behavior. These results suggest that 3-ketosteroid reduction is also not
      essential for estrous behavior facilitation by progestins.

PMID- 9610947
TI  - The relationship between intravenous cocaine self-administration and avidity for
      saccharin.
AB  - Two experiments were conducted to determine whether measures of saccharin intake
      could be used as a predictor of intravenous cocaine self-administration.
      Saccharin avidity, defined as the ratio of total daily fluid intake when
      saccharin and water were available to total intake when only water was available,
      was measured in male rats. Cocaine self-administration (0.4 mg/kg/infusion) was
      subsequently measured in an initial 18-h session, followed by daily 1-h sessions
      in which the infusion dose and the reinforcement schedule were varied. In the
      initial overnight session, some rats obtained the maximum or near-maximum number
      of infusions; this high level of cocaine intake was unrelated to saccharin
      avidity. In the remaining rats, there was a pattern somewhat resembling an
      "inverted-U," in which rats with low or high avidity self-administered less
      cocaine than those with intermediate avidity. This pattern reemerged later in the
      experiment when rats were tested at a low cocaine infusion dose combined with a
      FR-6 reinforcement schedule. In a second experiment, no significant relationship
      was observed between the self-administration of a lower cocaine dose (0.125
      mg/kg/infusion) and avidity for either saccharin or the artificial sweetener SC
      45647. Although these results are consistent with a previous report indicating no
      simple relationship between saccharin preference and the acquisition of cocaine
      self-administration, they do suggest that a more complex relationship may be
      observed under some conditions. Additional research with other drugs, as well as
      with caloric and noncaloric sweeteners, will be needed to determine the
      usefulness of taste measures in identifying or treating substance abuse.

PMID- 9610948
TI  - The role of dopamine and GABA in the frontal cortex of mice in modulating a motor
      stimulant effect of amphetamine and cocaine.
AB  - The results of previous studies have indicated that the activation of
      dopaminergic and GABAergic systems in the prefrontal cortex can decrease
      dopaminergic and glutamatergic activity in the striatum, ostensibly by the
      inhibition of corticofugal glutamatergic pathways. The present studies were
      designed to investigate the cortical influence of dopamine and GABA agonists and
      antagonists on the motor response to systemically administered amphetamine and
      cocaine in the mouse. The results show that both dopamine and THIP, the GABA(A)
      agonist, injected intracortically (i.c.) depress amphetamine- or cocaine-induced
      stereotypy. That these responses are functionally significant is illustrated by
      the i.c. effects of sulpiride and bicuculline; they enhance the motor activity of
      the stimulants, suggesting that both dopaminergic and GABAergic systems in the
      cortex are activated by systemically administered amphetamine or cocaine.
      Additional experiments demonstrated that bicuculline i.c. can antagonize the
      depressant effect of dopamine i.c.; therefore, the dopaminergic inhibition in the
      cortex appears to be mediated by the activation of a cortical GABA system. These
      results show that systemically administered amphetamine or cocaine causes
      dopaminergic effects not only in the striatum but also in the cortex, and that
      the dopaminergic effect in the cortex may activate a cortical GABAergic system,
      which in turn, may account for the noted cortical inhibition of the dopaminergic
      motor-stimulatory action in the striatum.

PMID- 9610949
TI  - Supraspinal flumazenil inhibits the antianalgesic action of spinal dynorphin A (1
      17).
AB  - DynorphinA (Dyn) administered intrathecally or released spinally in mice produces
      antianalgesia, that is, antagonizes morphine analgesia (tail-flick test). Spinal
      transection eliminates this Dyn antianalgesia. Present results in mice show that
      intracerebroventricular administration of flumazenil, a benzodiazepine receptor
      antagonist, also eliminated the antianalgesic action of Dyn; flumazenil in the
      brain eliminated the suppressant effect of intrathecal Dyn on intrathecal and
      intracerebroventricular morphine-induced antinociception. Intracerebroventricular
      clonidine, naloxone, and norbinaltorphimine release spinal Dyn. The latent
      antinociceptive actions of these compounds were uncovered by
      intracerebroventricular flumazenil. Thus, Dyn, given intrathecally or released
      spinally, activates a pathway that is inhibited by intracerebroventricular
      flumazenil. Dyn antianalgesia is not significantly altered by
      intracerebroventricular administration of bicuculline and picrotoxin, suggesting
      that activation of the gamma-aminobutyric acid receptor has little if any
      involvement in the antianalgesic action of Dyn. The antagonistic effect of Dyn
      seems to be mimicked by benzodiazepine agonists. Furthermore, administration of a
      benzodiazepine receptor inverse agonist (methyl-6,7-dimethoxy-4-ethyl-beta
      carboline-3-carboxylate) inhibited Dyn antianalgesia as did flumazenil. Thus,
      flumazenil, through a benzodiazepine antagonist or inverse agonist action,
      interrupts, as does spinal transection, the neuronal circuit (cord/brain/cord)
      necessary for the antianalgesic action of spinal Dyn. Because Dyn antianalgesia
      is an indirect action, activation of the neuronal circuit must lead to the
      release of a direct-acting antianalgesic mediator in the spinal cord.

PMID- 9610950
TI  - Effect of precipitated withdrawal on extracellular glutamate and aspartate in the
      nucleus accumbens of chronically morphine-treated rats: an in vivo microdialysis
      study.
AB  - Excitatory amino acids release during morphine or naloxone administration was
      studied in rats. Microdialysis in freely moving animals and capillary
      electrophoresis with laser-induced fluorescence detection were used to measure
      several amino acids including glutamate and aspartate in the extracellular fluid
      at the nucleus accumbens. Perfusion with a calcium-free Ringer's solution
      decreased glutamate and aspartate in nucleus accumbens dialysates to 35% of its
      baseline levels, suggesting partial synaptic origin of these amino acids. The
      first morphine injection decreased glutamate and aspartate to 50% of its baseline
      level. After repeated morphine injections this effect disappeared, suggesting
      tolerance. Naloxone injections to morphine-dependent rats increased 300%
      glutamate and aspartate release; these experiments suggest that excitatory amino
      acid release in the nucleus accumbens might play a role in morphine withdrawal.

PMID- 9610951
TI  - Brain beta-endorphin immunoreactivity as an index of cocaine and combined cocaine
      ethanol toxicities.
AB  - The present study examines alterations in the cytoplasmic immunoreactivity of
      brain beta-endorphin, an endogenous opioid peptide regarded as the mediator of
      both euphoria and antinociceptive systems, in relation to toxicities due to
      cocaine and combined cocaine-ethanol. Beta-endorphin-immunoreactive cells were
      visualized and counted in adjacent sections from male rat brains at the level of
      the arcuate nucleus. In this region, cytoplasmic beta-endorphin immunoreactivity
      is prevalent. An intraperitoneal injection of cocaine (75 or 15 mg/kg) was given
      15 min after an intraperitoneal injection of 3 g/kg ethanol or vehicle. With a
      fatally toxic dose (75 mg/kg) of cocaine, the number of neurons exhibiting
      cytoplasmic beta-endorphin immunoreactivity (immunoreactive nerve cells) was
      significantly increased immediately after the drug administration. Ethanol
      further enhanced the effects of both 15 and 75 mg/kg of cocaine. When the
      immunoreactivity was visually estimated by computer imaging analysis, lightly
      stained, weakly immunoreactive cells with photographic light absorption values
      greater than 50% were enhanced in the cocaine-ethanol groups compared to the
      cocaine only groups. Fatal toxicities were only observed in the groups treated
      with the high cocaine doses (75 mg/kg), with or without ethanol. In these groups,
      the number of strongly immunoreactive cells had increased significantly compared
      to the other groups. In the group treated with the high cocaine dose (75 mg/kg)
      plus ethanol, an increased frequency of late deaths that occurred over 1 h after
      the drug administration was observed, together with a decreased severity of
      cocaine-induced seizures and an early enhancement of weakly immunoreactive cells.
      Unlike the strongly immunoreactive cells, the weakly immunoreactive cells
      appeared to be continuously enhanced, based on an experiment examining beta
      endorphin immunoreactivity at 24 h after an injection of 50 mg/kg cocaine.

PMID- 9610952
TI  - Caffeine has similar pharmacokinetics and behavioral effects via the i.p. and
      p.o. routes of administration.
AB  - Caffeine administered intraperitoneally (i.p.) or orally (p.o.) decreased the
      reinforcement rate and increased the nonreinforced response rate in a dose
      related fashion under a differential reinforcement of low rate schedule (DRL 45
      s) in 3-h sessions. These effects were similar following both routes of caffeine
      administration. The parallel pharmacokinetics for i.p. and p.o. caffeine were
      each determined and related to the respective effects of caffeine on
      reinforcement rate. Serum caffeine concentrations were similar across the session
      after the absorption phase for a given dose. Consequently, the effect remained in
      approximately the same range within a dose, and no single dose possessed a full
      concentration-effect relation for the two routes. The effects of i.p. and p.o.
      caffeine on reinforcement rate plateaued at doses higher than 40 mg/kg, which
      produced a serum caffeine concentration of approximately 25 microg/ml regardless
      of the route of administration. The EC50 values were 7.34 and 9.93 microg/ml for
      i.p. and p.o. caffeine, respectively. This study as well as our previous studies
      demonstrated that the i.p. route is dependable for studying caffeine dose
      response relations but not for studying other drugs (e.g., midazolam). The
      possible mechanism accounting for this difference is discussed.

PMID- 9610953
TI  - The higher the dose, the greater the sex differences in escape-avoidance response
      in mice after acute administration of haloperidol.
AB  - Sex differences in the effects of haloperidol in the escape-avoidance response
      have previously been found in various studies carried out in our laboratory in
      which mice were used as experimental subjects. Males were more affected than
      females by the disruptive effects of this neuroleptic of frequent clinical use.
      In the present work these sex differences were evaluated in a unique training
      session using several doses of the drug (0.075, 0.25, and 0.75 mg/kg i.p.). The
      number of avoidances, escapes, nonresponses, crossings during the adaptation
      period, crossings during intertrial intervals, and response latencies were
      analyzed. Statistically significant sex differences were found in the number of
      escapes and nonresponses: males showed fewer escape responses and more
      nonresponses than females. These sex differences were dose dependent: a positive
      correlation was obtained between doses of haloperidol and sex differences
      observed in the number of escapes and nonresponses. The higher the dose, the
      greater the sex differences. These are related not only to the impairment of
      motor activity, because no sex differences were found in the number of crossings
      during the adaptation period and intertrial intervals.

PMID- 9610954
TI  - Monoaminergic dysregulation on diestrus-2 and estrus through high emotional
      reactivity.
AB  - Rats with great differences in emotional reactivity, during weighing and handling
      for vaginal smear screening were examined on diestrus-2 (DE-2), proestrus (PE),
      and estrus (E). Rats with high emotional reactivity (HR), interpreted as trait
      anxiety, had different serotonergic and dopaminergic profile in hypothalamus
      preoptic area (HY-PA) and striatum (Str) and thymus weight lower than that found
      in rats with low emotional reactivity (LR). In HY-PA of rats with HR when
      compared to rats with LR, increased 5-hydroxyindoleacetic acid (5-HIAA), 5
      HIAA/serotonin (5-HT) ratio, and 3,4-dihydroxyphenylacetic acid (DOPAC) and in
      Str increased DOPAC and DOPAC/dopamine (DA) ratio were found only on DE-2,
      paralleled by increased adrenal weight and decreased thymus weight. In Str, a
      significant effect of HR on 5-HIAA was found only on E, in parallel with
      increased 5-HT and decreased DOPAC and DOPAC/DA ratio when compared to rats with
      LR. The results suggest that activation of 5-HT and DA in HY-PA and DA in Str
      through HR is apparent only on DE-2 while, conversely, on E suppression of
      striatal DA it is apparent with 5-HT dysregulation. These findings might have
      some relevance to the predisposition of women with trait anxiety to premenstrual
      syndrome.

PMID- 9610955
TI  - Individual differences in the feeding and locomotor stimulatory effects of acute
      and repeated morphine treatments.
AB  - Rats with high propensity to ingest sugar (HIGH) show increased responsiveness to
      amphetamine treatments than rats with low propensity to ingest sugar (LOW).
      Intrinsic variation in the functioning of the mesolimbic dopamine system has been
      suggested to account for these individual differences. Morphine has stimulatory
      effects on feeding and locomotion that are in part mediated by the mesolimbic
      dopamine system. The present study therefore examined whether LOW and HIGH rats
      would exhibit differences in the feeding and locomotor stimulating effects of
      morphine. Morphine (1, 2, and 4 mg/kg) significantly stimulated the intake of
      chow and sugar in LOW rats without affecting food consumption in HIGH rats.
      Further, it was found that both groups of rats did most of their feeding in the
      first 20 min following injection, and that the stimulatory effect of morphine in
      LOW rats was restricted to the first hour of the 3-h test session. Repeated
      morphine (2 mg/kg) stimulated sugar intake in LOW but not HIGH rats, and there
      was no evidence of increased intake across injections. Acute administration of
      5.0 mg/kg, but not 2.0 mg/kg, of morphine produced higher levels of locomotor
      activity in LOW rats compared to HIGH rats; repeated treatment with 5.0 mg/kg
      morphine produced a sensitized locomotor response in both LOW and HIGH rats.
      These results indicate that LOW rats exhibit increased responsiveness to the
      locomotor and feeding stimulatory effects of morphine compared to HIGH rats. One
      implication arising from these findings is that LOW and HIGH rats may be
      distinguished by differences in opiatergic function, as well as by differences in
      dopaminergic function.

PMID- 9610956
TI  - Chronobiological patterns of onset of acute cerebrovascular diseases.
AB  - There is a considerable amount of data indicating that several major unfavorable
      cerebrovascular events are not randomly distributed over time, but show a
      peculiar distribution along the day, the week, and the months of the year. The
      authors review the available evidence on the chronobiological (circadian, weekly,
      and seasonal) patterns of onset of acute cerebrovascular diseases and variations
      in their possible triggering mechanisms. The existence of a peculiar
      chronobiological pattern in the onset of acute cerebrovascular disease,
      characterized by both circadian (morning and evening occurrence), circaseptan
      (last and first days of the week), and circannual (especially in winter) is
      confirmed, although differences depending on biological (gender, age),
      pathological (diabetes, hypertension, smoke, alcohol), cultural, social, and
      environmental factors exist. A deeper knowledge of the underlying
      pathophysiologic mechanisms could provide more effective insights for both
      preventive strategies and optimization of therapeutic approach.

PMID- 9610958
TI  - Delayed treatment with desulfato-hirudin prevents fibrin formation in
      lipopolysaccharide-induced shock.
AB  - Previous work has shown that pre-treatment with the thrombin inhibitor
      recombinant desulfato-hirudin prevented fibrin formation and respiratory
      dysfunction in porcine lipopolysaccharide shock. We examined the effects of
      delayed administration of recombinant desulfato-hirudin in bacterial
      lipopolysaccharide shock. Miniature pigs were studied under anaesthesia and
      ventilation, and received a bacterial lipopolysaccharide infusion (2 microg/kg/h)
      for 7 h; recombinant desulfato-hirudin was started 1 h after bacterial
      lipopolysaccharide in 10 animals (bolus 12.9 nmol/kg; continuous infusion 6.5
      nmol/ kg/h); 10 randomised control animals received saline instead of recombinant
      desulfato-hirudin. Fibrin and thrombin-antithrombin complex levels in plasma were
      significantly lower in bacterial lipopolysaccharide+recombinant desulfato-hirudin
      animals than in controls. Both groups displayed a similar rise in pulmonary
      vascular resistance and other parameters of lung dysfunction; only lung tissue
      wet/dry ratio was lower in recombinant desulfato-hirudin-treated than in control
      animals. Both groups had similar circulatory alterations. Recombinant desulfato
      hirudin interrupted coagulation activation during ongoing bacterial
      lipopolysaccharide-induced shock in pigs even when administered with a delay of
      one hour after start of the bacterial lipopolysaccharide infusion. A protective
      effect of delayed recombinant desulfato-hirudin administration on bacterial
      lipopolysaccharide-induced acute lung injury and alterations in the systemic
      circulation could not be demonstrated in this experiment.

PMID- 9610957
TI  - Endothelial cell markers in chronic uremia: relationship with hemostatic defects
      and severity of renal failure.
AB  - Plasma von Willebrand factor antigen, soluble thrombomodulin, and tissue factor
      were increased in 31 patients with severe chronic renal failure (creatinine
      clearance <20 ml/min) under conservative treatment, whereas plasminogen activator
      inhibitor antigen did not differ significantly from healthy controls. No
      correlation among plasma levels of these proteins was found. Three patterns of
      relationship between endothelial cell markers and hemostatic defects were
      identified: 1) Plasma thrombomodulin, a marker of endothelium damage, was found
      an independent predictor of bleeding time and platelet aggregation, and secretion
      defects, and was also related to the severity of renal failure; 2) von Willebrand
      factor antigen, an index of endothelial cell activation and secretion, was
      significantly correlated with intravascular markers of thrombin and plasmin
      generation and with platelet adenosine triphosphate content, but not with plasma
      creatinine levels; and 3) tissue factor and plasminogen activator inhibitor
      antigen levels were not statistically correlated with the diverse hemostatic
      defects. Activation of coagulation and fibrinolysis, secondary to endothelial
      cell activation, appearing early during the evolution of chronic renal failure,
      is pathogenically related to the platelet dysfunction, and probably to
      development of atherosclerosis and thrombotic events in this disease. The
      progression of chronic renal failure, through endothelial cell damage, would lead
      to aggravation of the platelet functional defect potentiating the hemorrhagic
      risk.

PMID- 9610960
TI  - Low density lipoprotein receptor-related protein (LRP) expression varies among
      Hep G2 cell lines.
AB  - The multiligand receptor, low density lipoprotein receptor-related protein (LRP),
      is implicated in processes such as atherosclerosis and fibrinolysis through its
      mediation of the catabolism of lipoproteins, proteases, and protease inhibitor
      complexes. The hepatoma cell line Hep G2 expresses LRP and has been used widely
      to investigate the catabolism of LRP ligands including tissue-type plasminogen
      activator (tPA). However, the mechanism and degree by which tPA interacts with
      Hep G2 has been reported with some inconsistencies which may reflect variation in
      their level of LRP expression. To address this possibility we characterized,
      antigenically and functionally, LRP expression in high and low passage Hep G2
      cells both from the parental line (ATCC sourced) and a cloned subline, a16. The
      LRP contribution to 125I-tPA binding varied from 65% for high passage a16 cells,
      to 20% for low passage parent cells as quantified by inhibition in the presence
      of 39-kD receptor associated protein (RAP) which prevents binding of all known
      LRP ligands. The same trend in LRP expression among Hep G2 sublines was further
      evident in their ability to degrade 125I-tPA and survive Pseudomonas exotoxin A
      challenge. These results imply wide variability in basal LRP expression among Hep
      G2 lines dependent on cell lineage and long-term culture conditions.

PMID- 9610959
TI  - Measurement of fibrinogen in frozen plasma.
AB  - Several large studies have compared fibrinogen measurements determined over a
      particular time interval. These assays are subject to difficulties encountered by
      all laboratories on tests carried out over a period of time such as assay drift.
      To avoid this problem, plasma can be stored frozen and fibrinogen determined in a
      large number of samples simultaneously. However, a thorough comparison of
      measurements carried out in fresh and frozen plasma has not yet been performed.
      Fibrinogen concentration was therefore determined in fresh plasma samples and
      then at a later date in the same samples after storage at -70 degrees C. A good
      correlation was observed between the two measurements, however, bias increased at
      the higher fibrinogen levels which are most critical in the determination of
      thrombotic risk. An increase in measurement error as a result of freezing was
      also observed. These effects may, therefore, be important considerations in
      future studies of this nature.

PMID- 9610961
TI  - Effective anticoagulation by argatroban during coronary stent implantation in a
      patient with heparin-induced thrombocytopenia.

PMID- 9610962
TI  - Indium-111 DTPA-heparin: pharmacokinetics and biodistribution following
      subcutaneous administration in rat and rabbit.

PMID- 9610963
TI  - One-week survey of pain intensity on admission to and discharge from the
      emergency department: a pilot study.
AB  - The purpose of this pilot study was to determine the incidence and severity of
      pain intensity in patients 4 years of age and older presenting to the noncritical
      ward of the emergency department (ED). All patients presenting to the ED of two
      university hospitals (one general, one pediatric) who were triaged to the
      noncritical ward during 12 h/day for 1 week were asked to report their pain
      intensity on admission and again asked just prior to discharge home. The
      chromatic analogue scale with a range of 0-10 was used as the measure of pain
      intensity. Pain reports were obtained from half of all patients (58% of adults,
      47% of children) admitted during the study week. Approximately one-third (29% of
      adults and 31% of children) reported no pain on admission, but half of both age
      groups (52% of adults, 48% of children) reported pain 4/10 or higher. On
      discharge, one-third of both groups reported pain 4/10 or higher. Eleven percent
      of both adults and children reported pain 1.5/10 or higher on discharge than on
      admission. Adult patients with musculoskeletal complaints had the highest pain
      intensities (mean score admission-discharge, 5.6-4.7/10; other categories, <5).
      For children, neurological complaints, exclusively headaches, were highest (mean
      score admission-discharge, 4.8-5.2/10; other categories, <5). Children
      accompanied by their mothers alone had poorer pain improvement (no change) than
      children accompanied by their fathers alone or both parents (score improvement of
      1). It thus appears that pain is a problem for the majority of patients
      presenting to the ED. An important percentage of patients leave the ED with more
      pain than when they arrived. Further investigation is warranted to determine
      factors predicting poor pain resolution during an ED visit.

PMID- 9610965
TI  - Victims of the Palestinian uprising (Intifada): a retrospective review of 220
      cases.
AB  - The purpose of this study was to review the cases of the victims of the
      Palestinian uprising (Intifada) and to describe the clinical presentations, the
      types of weapons used, and the different sites of injuries. This is a
      retrospective chart review study of the patients who were injured during the
      Palestinian uprising in the period April 1993-April 1994 and treated in the
      emergency department of the Barzilai Medical Center, Ashkelon, Israel. The
      Barzilai Medical Center is a regional level II trauma referral general hospital.
      Two hundred and twenty patients were injured during the Palestinian uprising and
      referred to our emergency department. Forty-one patients were citizens of the
      Gaza area, 26 patients were Israeli civilians, and 153 were Israeli soldiers.
      There were 55 patients (25%) injured by firearms, 10 patients (4.5%) by
      explosives, and 120 (54.5%) by striking stones. Seventy-three patients (33.2%)
      were hospitalized, and 22 patients needed surgery. The most commonly injured part
      of the body was the lower limb among the Gaza citizens and the head and neck
      among the Israeli soldiers and civilians. Striking stones was the most common
      means of injury used by the Palestinians, and stab wounds by knives and other
      sharp objects were the most common injuries among Israeli civilians. None of the
      patients suffered direct blast injuries. The Palestinian uprising resulted in
      many victims and disabled people in both nations. Terrorism did not cease after
      the peace treaty. It changed its face and moved from Gaza to the center of
      Israel. Suicidal terrorist bombing in public spaces and public buses carries more
      danger and more victims with much more severe injuries. We hope that the future
      will be brighter, and both nations will eventually be able to live in peace.

PMID- 9610964
TI  - Intravenous propafenone for converting recent onset atrial fibrillation in
      emergency departments: a randomized placebo-controlled multicenter trial. FAPS
      Investigators Study Group.
AB  - Atrial fibrillation (AF) is one of the most frequent dysrhythmias in patients
      coming to emergency departments (EDs), and pharmacological treatment is
      frequently performed. The aim of this randomized placebo-controlled multicenter
      trial was to compare propafenone (a class 1C antidysrhythmic agent), administered
      i.v. in the ED, with placebo in the treatment of recent-onset AF (<72 h). We
      randomly allocated 156 patients (88 males; 68 females) from 18 to 80 years old,
      with recent-onset AF, to receive i.v. propafenone (2 mg/kg for 10 min) or the
      matching placebo. The patients were followed for 2 h. Exclusion criteria were the
      presence of one of the following: lack of informed consent, clinical evidence of
      heart failure, clinical hyperthyroidism, recent acute myocardial infarction,
      atrioventricular block, cardiac valve dysfunction, a history of bronchial asthma,
      and current treatment with antidysrhythmic agents including digitalis. The two
      groups did not differ significantly in terms of sex, age, body weight, or
      estimated time elapsed since the beginning of atrial fibrillation. Conversion to
      sinus rhythm occurred in 13 of the 75 patients who received the placebo (17.3%)
      and in 57 of the 81 patients who were given propafenone (70.3%). In conclusion,
      intravenous propafenone administration in the ED can be considered a safe and
      effective approach for converting AF to sinus rhythm.

PMID- 9610966
TI  - Sustained effect of an intervention to limit ordering of emergency department
      lumbosacral spine films.
AB  - Attempts at modification of test-ordering practices among housestaff demonstrate
      reversion to prior behavior after relaxation of surveillance. To test the
      hypothesis that use of pre-specified criteria for obtaining emergency department
      (ED) lumbosacral spine (LSS) films would reduce LSS utilization, we designed a
      cross-sectional observational study, with 1-year follow-up. The primary endpoint
      was estimate of efficacy, expressed as a proportionate change in LSS films from
      1982 to 1992, adjusted for ED volume. The secondary endpoint was estimate of
      safety of this protocol. We found a 28% proportionate decrease in LSS films from
      1982 to 1992. Among 520 patients with back complaints not meeting criteria for
      films, 4 had serious back pathology on follow-up that may have been detected on
      the index ED visit if LSS films had been ordered. All four were HIV(+), three of
      whom initially denied, then subsequently admitted, to active intravenous drug
      use. We conclude that use of a simple requisition form is associated with a
      quantitatively and statistically significant sustained reduction in utilization
      of ED LSS radiography. This protocol appears to provide a safe, cost-efficient
      means of limiting LSS film ordering by housestaff, with the possible exception of
      HIV(+) individuals. Because the association between HIV and radiographic
      abnormalities may be confounded by intravenous drug use, we cannot determine, on
      the basis of our data, whether HIV(+) status should be considered an independent
      criterion for obtaining LSS films.

PMID- 9610967
TI  - Magnetic resonance imaging in the early diagnosis of group A beta streptococcal
      necrotizing fasciitis: a case report.
AB  - Early diagnosis of invasive group A beta streptococcal (GABS) infection has been
      achieved in a patient using magnetic resonance imaging (MRI) complemented by
      needle aspiration. Life-saving treatments of GABS infection that include
      immediate surgical debridement along with the administration of i.v. antibiotics,
      gamma globulin, and hyperbaric oxygen were then implemented successfully to
      prevent the development of streptococcal toxic shock syndrome. While MRI is
      valuable in making early diagnosis of GABS, it should not delay surgical
      intervention.

PMID- 9610968
TI  - Cold injury from pressurized liquid ammonia: a report of two cases.
AB  - Patients exposed to pressurized liquids or gases present unique diagnostic and
      treatment challenges to the Emergency Physician. The potential for injury depends
      upon the properties of the chemical in addition to the thermodynamic effects from
      exposure to a pressurized substance. We present two cases of exposure to
      pressurized ammonia during an industrial accident. One patient's symptoms were
      consistent with an ammonia alkali burn, whereas the other patient's symptoms were
      more characteristic of a significant thermal injury caused by the rapid expansion
      and evaporation of a pressurized liquid.

PMID- 9610969
TI  - Fatal pulmonary barotrauma due to obstruction of the central circulation with
      air.
AB  - Cardiac arrest in cases of barotraumatic arterial gas embolism (AGE) is usually
      ascribed to reflex dysrhythmias secondary to brainstem embolization or secondary
      to coronary artery embolization. Several case reports suggest that obstruction of
      the central circulation (i.e., the heart, pulmonary arteries, aorta, and arteries
      to the head and neck) may play a role in the pathogenesis of sudden death in
      victims of pulmonary barotrauma. We report three consecutive cases of fatal AGE
      in patients in whom chest roentgenograms demonstrated confluent air lucencies
      filling the central vascular bed, the heart, and great vessels. In none of the
      victims was there evidence by history or at autopsy that the intravascular gas
      was iatrogenically introduced. Total occlusion of the central vascular bed with
      air is a mechanism of death in some victims of AGE, and resuscitation efforts for
      such patients should take this possibility into consideration.

PMID- 9610970
TI  - Intravenous vitamins for alcoholics in the emergency department: a review.
AB  - It is common practice for emergency physicians to provide i.v. vitamin
      replacements for alcoholics who present to the emergency department (ED). This
      article describes vitamin deficiencies in alcoholics and reviews the utility and
      utilization of vitamins in the emergency department. We conclude that the current
      data do not support the routine administration of i.v. vitamins to alcoholics who
      present to the ED and we do not recommend this practice.

PMID- 9610971
TI  - Childhood risks from the ferret.
AB  - The ferret is becoming an increasingly popular pet, yet the dangers of ferret
      ownership remain unrecognized by physicians and the general public. Reported are
      three incidents of ferret attacks in a 3-month period of time. The risk of attack
      is greatest in infants and small children. Wounds caused by ferret attacks must
      be evaluated for injury, infection, and rabies prophylaxis. Such attacks should
      be reported to animal control authorities. Physicians need to recognize the
      ferret as a risk to children.

PMID- 9610972
TI  - Carbon monoxide poisoning presenting as an isolated seizure.
AB  - Seizures are generally regarded as a manifestation of extreme, generally near
      fatal carbon monoxide poisoning. A case is described in which a seizure
      attributable to carbon monoxide poisoning occurred in a small child at a level
      not thought to be associated with serious neurologic toxicity. A literature
      review of the occurrence of seizures in carbon monoxide poisoning found that no
      particular degree of carboxyhemoglobin was correlated with the presence of
      seizures. A seizure with no other apparent cause occurring in circumstances in
      which carbon monoxide toxicity would be suspected can be attributed to carbon
      monoxide poisoning.

PMID- 9610973
TI  - Hemiparesis and altered mental status in a child after glyburide ingestion.
AB  - A normally healthy 6-year-old woke in an agitated state, limp, and moving only
      her left extremities. Upon arrival at the emergency department, a blood glucose
      measurement was 34 mg/dL. The child was lethargic, not responding to questions
      appropriately, and not moving her right extremities. The right arm was flexed,
      and the right leg was flexed and abducted. Pupils were equal and reactive, and
      eyes were deviated to the left. Six loose tablets of the grandmother's glyburide
      were found at home in the child's outdoor playhouse. Administration of glucose
      produced no change in the child's clinical condition. Intravenous glucose was
      begun at 4 mg glucose/kg/min, and the blood glucose level did not fall below 74
      mg/dL after that. Over the next 48 h, the hemiparesis and mental status changes
      resolved without sequelae. The events of the case suggest a hypoglycemia-induced
      seizure with subsequent Todd's paralysis. Early direct medical evaluation in
      suspected glyburide ingestions in children is suggested.

PMID- 9610974
TI  - Lyme disease complicated by the Jarisch-Herxheimer reaction.
AB  - A 31-year-old woman diagnosed with Lyme disease was treated with amoxicillin. One
      hour after the first antibiotic dose, the patient became acutely ill. She
      developed hypertension, fever, and rigors. Shortly afterward, she became
      hypotensive and required fluid resuscitation. This systemic illness, the Jarisch
      Herxheimer reaction, was first noted in association with antibiotic therapy for
      neurosyphilis. Thus, the institution of antibiotic therapy may be complicated by
      the Jarisch-Herxheimer reaction.

PMID- 9610975
TI  - Overview of evacuation and transport of patients following the 1995 Hanshin-Awaji
      earthquake.
AB  - We investigated how patients were evacuated and transported from affected
      hospitals in the disaster area to backup hospitals following the 1995
      catastrophic Hanshin-Awaji earthquake. A retrospective review was conducted of
      medical records of 6107 patients hospitalized during the first 15 days after the
      earthquake, collected from 48 affected hospitals in the disaster area and 47
      backup hospitals in the surrounding area. Of the 6107 patients, a total of 2290
      (38%) were transferred to backup hospitals, consisting of 187 patients (50%) with
      crush syndrome, 702 (26%) with other traumas, and 1401 (41%) with illness. Of
      those 2290 patients, 1741 (76%) were transferred from affected hospitals to
      backup hospitals, while 549 patients (24%) were evacuated directly to backup
      hospitals. The peak in transport came during the first 4 days. The family car was
      the most frequently used means of transport; ambulance was used in only 26% of
      cases, and helicopters were used minimally. There was no notable difference in
      the percentage of intensive care patients and nonintensive care patients
      transferred to backup hospitals. The mortality rate for patients with trauma and
      crush syndrome was significantly higher in the affected hospitals. These results
      suggest that the existing emergency medical service system was not adequate for
      this urban earthquake. From our vantage point, we are keenly aware of the need
      for improved communications between hospitals, a well equipped patient transport
      system, and a well coordinated disaster response mechanism.

PMID- 9610976
TI  - Pisiform and hamulus fractures: easily missed wrist fractures diagnosed on a
      reverse oblique radiograph.
AB  - We present a review of the current literature involving fractures of the pisiform
      and hook of the hamate. This is highlighted by two cases in which the fracture
      lines are seen only on the reverse oblique wrist radiograph, a view obtained with
      the wrist in a supinated rather than a pronated position. These fractures are not
      seen on standard two or three view wrist examination. Both of these fractures
      were initially missed in the emergency department. Serious sequelae can result
      from both of these injuries and can be avoided if diagnosed acutely. The reverse
      oblique radiograph can be quick, cost-effective, and diagnostic in this setting.
      If properly treated by immobilization or excision, the results can be excellent.

PMID- 9610977
TI  - Mechanical ventilation: past and present.
AB  - Emergency physicians commonly manage patients with acute respiratory failure who
      require assisted mechanical ventilation. Several different modes of positive
      pressure mechanical ventilation can be used to manage these patients when they
      present to the emergency department. These modes of ventilation have evolved over
      the last three decades. A comprehensive review of the most important historical
      moments in mechanical ventilation as well as the different modes commonly used in
      the emergency department are presented. In addition, new techniques in
      noninvasive mechanical ventilation are presented.

PMID- 9610978
TI  - Inadequate standard for glove puncture resistance: allows production of gloves
      with limited puncture resistance.
AB  - The National Fire Protection Association has developed standards for glove
      puncture resistance using a metal puncture probe. Biomechanical performance
      studies have demonstrated that glove puncture resistance to the probe is
      significantly greater than that of the hypodermic needle, suggesting that these
      standards have no clinical relevance. These standards give a false sense of
      security to health care personnel and sanction the production and use of gloves
      that give inadequate protection. The result is potentially harmful for medical
      personnel.

PMID- 9610979
TI  - Propofol bolus facilitates reduction of luxed temporomandibular joints.
AB  - "Locked" or dislocated temporomandibular joint (TMJ) is a common problem in
      emergency medicine. Like many other joint dislocations, the repositioning of the
      joint can be facilitated by conscious sedation and muscular relaxation. Propofol
      is a useful agent for use in the emergency department because of its extremely
      short half-life, its antiemetic properties, and its safety record. We report two
      cases of locked TMJ that were repositioned under sedation with propofol. We
      review methods for repositioning the locked TMJ and review appropriate agents for
      sedation and muscular relaxation.

PMID- 9610980
TI  - Nalmefene: a long-acting opioid antagonist. Clinical applications in emergency
      medicine.
AB  - The use of the opioid antagonist naloxone is well known to the experienced health
      care provider. The availability of the longer acting opioid antagonist nalmefene
      has several potential benefits in clinical practice. Nalmefene has a plasma half
      life of almost 11 h, compared to 60-90 min for naloxone. Nalmefene has been shown
      to reverse opioid intoxication for as long as 8 h, reducing the need for
      continuous monitoring of intoxicated patients and repeated dosing of naloxone.
      Single dose administration has also been used effectively in the reversal of
      opiate-assisted conscious sedation. In addition, this agent has been used in the
      treatment of diseases as diverse as interstitial cystitis and chronic alcohol
      dependence. However, the long duration of action enables extended withdrawal
      reactions in the chronically opioid-dependent patient. The prolonged opioid
      antagonism of nalmefene has several applications in the clinical practice of
      emergency medicine, and is a useful addition in certain situations to the
      pharmacologic armamentarium of the practicing emergency physician.

PMID- 9610981
TI  - Angioedema.

PMID- 9610982
TI  - Ludwig's angina.

PMID- 9610983
TI  - Elegant emergency medicine.

PMID- 9610984
TI  - Resource utilization in the emergency department.

PMID- 9610985
TI  - Etomidate and propylene glycol toxicity.

PMID- 9610986
TI  - Injury prevention and control.
AB  - Despite recent efforts to apply a public health epidemiology to violence in
      America, most physicians do not incorporate violence prevention methodologies
      into their own individual practices. The challenge of integrating violence
      detection, prevention, and management into the delivery of health care begins by
      building on the recent successful implementation of injury prevention and control
      policies. Three specific issues that physicians can address in their individual
      practice settings are reviewed: 1) alcohol and substance abuse, 2) firearms, and
      3) family violence. This article focuses on these issues and addresses the
      concept of the physician as an advocate for change.

PMID- 9610987
TI  - Resource utilization in the emergency department: the duty of stewardship.
AB  - As the pool of available health care resources continues to evaporate, emergency
      physicians will be increasingly required to guard against the provision of
      expensive, unnecessary, and marginally beneficial care. This article proposes
      that emergency physicians embrace the ethic of prudent resource stewardship to
      ensure the continued availability of emergency services to all who need them.
      When making resource allocation decisions, emergency physicians must consider the
      likelihood, magnitude, and duration of benefits to patients, the urgency of the
      condition, and the cost and burdens of treatment to patients, payers, and
      society. These considerations go beyond professional duties to individual
      patients and suggest that ignoring the burdens of emergency department
      microallocation decisions is socially and morally irresponsible.

PMID- 9610988
TI  - CAEP issues. The Canadian Triage and Acuity Scale: a new and critical element in
      health care reform. Canadian Association of Emergency Physicians.

PMID- 9610989
TI  - Maternal body composition near term and birth weight.
AB  - OBJECTIVE: To assess the relative influence of maternal body composition at late
      gestation on birth weight. METHODS: Maternal body composition was estimated in
      224 women near term using a deuterium dilution technique. Using a stepwise
      multiple linear regression analysis, we studied the association with birth weight
      of eight factors, including maternal fat-free mass and fat mass. RESULTS:
      Maternal fat-free-mass was the most important variable influencing birth weight
      (R2 = .144, P < .001), followed by maternal fat mass (R2 = .051, P < .001).
      Gestational age at delivery was the third strongest influence on birth weight (R2
      = .047, P < .001). CONCLUSION: In late pregnancy, fat-free mass was the most
      important maternal body component associated with birth weight. The
      implementation of longitudinal studies could shed more light on the influence of
      maternal body composition on birth weight.

PMID- 9610990
TI  - An empiric evaluation of the Institute of Medicine's pregnancy weight gain
      guidelines by race.
AB  - OBJECTIVE: To examine associations between pregnancy weight gain outside and
      within ranges recommended by the Institute of Medicine and birth weight by both
      prepregnant body mass index (BMI) and race-ethnicity. METHODS: Mean birth weight
      and incidence of term low birth weight (LBW, less than 2500 g) and high birth
      weight (more than 4500 g) were compared across BMI-pregnancy weight gain-race
      ethnicity strata. Subjects were 173,066 white, black, and Hispanic low-income
      pregnant women attending prenatal nutrition programs between 1990 and 1993.
      RESULTS: Among low and average BMI women (all race-ethnicity groups), weight gain
      within Institute of Medicine ranges resulted in significant LBW reductions;
      further LBW reductions at gains beyond Institute of Medicine ranges were offset
      by increasing high birth weight risk. Among women of high and obese BMI, LBW
      trends were less pronounced; thus, the benefit of gaining within the Institute of
      Medicine range was less apparent. Although blacks in every BMI-weight gain
      category had lower mean birth weights than white women, gaining in the upper end
      of the Institute of Medicine ranges did not provide a consistent LBW reduction
      for black women; adjusted LBW odds ratios and 95% confidence intervals for gains
      in the upper relative to the lower half of the Institute of Medicine range were
      1.3 (0.8, 2.1), 0.7 (0.5, 1.03), 0.3 (0.2, 0.8), and 1.3 (0.7, 2.5) for black
      women of low, average, high, and obese BMI, respectively. CONCLUSION: Institute
      of Medicine pregnancy weight gain ranges recommended for low and average BMI
      women appear reasonable, but recommendations for high and obese BMI women require
      further evaluation. The recommendation that black women in all BMI groups strive
      for gains toward the upper ends of the ranges is not supported clearly by these
      data.

PMID- 9610992
TI  - Alcohol use and pregnancy: improving identification.
AB  - OBJECTIVE: To test the effectiveness of a four-item prenatal-alcohol-use, self
      administered screening questionnaire that asks about tolerance to alcohol, being
      annoyed by other's comments about drinking, attempts to cut down, and having a
      drink first thing in the morning ("eye-opener") (T-ACE) in an ethnically and
      socioeconomically diverse sample. METHODS: Two hundred fifty T-ACE-positive and
      100 T-ACE-negative women completed a comprehensive assessment of their alcohol
      use after initiating prenatal care at the Brigham and Women's Hospital in Boston,
      Massachusetts. This comprehensive assessment, which included the Alcohol Use
      Disorders Identification Test and the Short Michigan Alcoholism Screening Test as
      comparisons to the T-ACE, generated three criterion standards: Diagnostic and
      Statistical Manual of Mental Disorders, Third Ed., Revised (DSM-III-R), lifetime
      alcohol diagnoses, risk drinking (regularly having more than one fluid ounce of
      alcohol per drinking day before pregnancy), and current drinking. RESULTS: T-ACE
      positive pregnant women were more likely than T-ACE-negative women to satisfy DSM
      III-R criteria for lifetime alcohol diagnoses (40% versus 14%, P < .001) and risk
      drinking (39% versus 8%, P < .001) and to have current alcohol consumption (43%
      versus 13%, P < .001). In contrast, obstetric staff members documented only 33
      (9%) women as using alcohol at any time, even though nearly all subjects (96%)
      were asked about drinking upon initiation of prenatal care. CONCLUSION: The T-ACE
      was the most sensitive screen for lifetime alcohol diagnoses, risk drinking, and
      current alcohol consumption. It outperformed obstetric staff assessment of any
      alcohol use by pregnant women enrolled in the study.

PMID- 9610991
TI  - Improved birth outcomes associated with enhanced Medicaid prenatal care in drug
      using women infected with the human immunodeficiency virus.
AB  - OBJECTIVE: To evaluate the effectiveness of an intervention designed to enhance
      Medicaid prenatal care in improving birth outcomes of drug-using women infected
      with the human immunodeficiency virus (HIV). METHODS: Medicaid and vital
      statistics records were linked for 353 HIV-infected drug-using women delivering
      in 1993 and 1994 while enrolled in New York State Medicaid. Of these, 68% were
      treated by providers participating in the Prenatal Care Assistance Program,
      designed to provide case management, improved continuity, referral services, and
      behavioral risk reduction counseling. In a series of logistic models, we
      estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of low
      birth weight (less than 2500 g) and preterm delivery (before 37 weeks), comparing
      women using and not using the program. RESULTS: Women using the Prenatal Care
      Assistance Program were significantly less likely, after adjustments were made
      for maternal characteristics, to have low birth weight infants and preterm
      deliveries (OR 0.52, 95% CI 0.31, 0.89; and OR 0.57, 95% CI 0.34, 0.97,
      respectively). Adding measures of greater adequacy and continuity of prenatal
      care to the models explained just over 20% of the Prenatal Care Assistance
      Program's protective effect. The addition of maternal high-risk behavior, HIV
      focused care, and drug use treatment variables altered program effect estimates
      less profoundly (together accounting for 4 and 9% of the program's protection
      against low birth weight and preterm delivery, respectively). CONCLUSION: The
      Prenatal Care Assistance Program appeared to be successful in reducing the
      incidence of low birth weight and preterm delivery in this high-risk population.
      The program's success can be attributed, in part, to increased adequacy and
      continuity of prenatal care and, to a lesser extent, to more frequent receipt of
      special services and reduced maternal high-risk behaviors.

PMID- 9610993
TI  - Maternal hypertension and spontaneous preterm births among black women.
AB  - OBJECTIVE: To examine effects of maternal hypertension on spontaneous preterm
      birth (birth at less than 37 weeks' gestation) among black women. METHODS: Using
      hospital discharge summary records from the National Hospital Discharge Survey
      between 1988 and 1993, we conducted a case-control study to assess the risk of
      spontaneous preterm birth among black women with chronic hypertension preceding
      pregnancy and pregnancy-induced hypertension. Logistic regression was used to
      derive odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Preterm
      births were almost two times more likely for women with pregnancy-induced
      hypertension (OR = 1.8; 95% CI, 1.5, 2.2), more than 1.5 times more likely for
      women with chronic hypertension preceding pregnancy (OR = 1.6; 95% CI, 1.3, 2.1),
      and more than four times more likely for women with pregnancy-aggravated
      hypertension (OR = 4.4; 95% CI, 2.9, 6.7) compared with normotensive women.
      Preterm births also were associated significantly with antepartum hemorrhage,
      poor fetal growth, marital status, and source of payment. The odds of preterm
      birth by maternal hypertension were increased among women with chronic
      hypertension and genitourinary infection, whereas the odds of preterm birth were
      reduced among women with pregnancy-induced hypertension and genitourinary
      infection. CONCLUSION: These findings are important in demonstrating the relation
      between type of hypertension in pregnancy and preterm birth. The relationships
      between maternal hypertension and preterm birth need to be further investigated
      to provide some guidelines in the management of hypertension in pregnancy and
      assessment of prenatal care compliance for black women, particularly when
      genitourinary infection is present.

PMID- 9610994
TI  - Pregnancy outcomes following sonographic nonvisualization of the fetal stomach.
AB  - OBJECTIVE: To review pregnancy outcomes when two or more ultrasound scans
      persistently fail to visualize the fetal stomach. METHODS: A computerized
      ultrasound database was used to identify all fetuses in which two or more serial
      ultrasound examinations failed to visualize the fetal stomach. Sonographic images
      were reviewed retrospectively, with the reviewer blinded to outcome data, to
      confirm persistent nonvisualization. Pregnancy outcome data were obtained from
      hospital charts and physicians' office records. Fetal karyotypes, when performed,
      were obtained from amniotic fluid (AF) culture. The ultrasound findings then were
      compared with fetal karyotype results and pregnancy outcome data. RESULTS: Of
      35,569 ultrasound scans performed during 1991-1996, 26 fetuses (0.07%) with
      persistently nonvisualized stomachs were identified. Structural defects were
      detected in 17 fetuses (65%), most often involving the cardiothoracic (n = 5),
      genitourinary (n = 4), and central nervous systems (n = 4). Karyotypes were
      obtained in 12 fetuses, and four of them were abnormal. Only five of 17 fetuses
      (29%) with a structural defect survived. In nine of 26 fetuses (35%) with
      persistently nonvisualized stomachs, no structural defect was identified. Each of
      these nine fetuses had abnormal AF volume in its surrounding sac, and the overall
      perinatal survival in fetuses without a structural defect was only 50%.
      CONCLUSION: Fetuses with persistently nonvisualized stomachs have an increased
      incidence of structural defects and AF abnormalities and are more likely to have
      a poor outcome. A detailed ultrasound examination and fetal karyotype analysis
      should be performed to evaluate fetuses with persistently nonvisualized stomachs.

PMID- 9610995
TI  - Predictors of neonatal resuscitation, low Apgar scores, and umbilical artery pH
      among growth-restricted neonates.
AB  - OBJECTIVE: To identify risk factors associated with poorer immediate neonatal
      outcomes among growth-restricted neonates. METHODS: Records of all 530 growth
      restricted neonates born between January 1989 and February 1995 were reviewed.
      Outcomes included resuscitation measures, Apgar scores, and umbilical blood gas
      values. Neonates were assigned to one of six anesthetic groups, and outcomes were
      compared. Predictors of poorer outcomes were examined using logistic and linear
      regression. RESULTS: Neonates exposed to general anesthesia were more likely to
      be intubated (37.9% versus 4.1%, P < .001, Pearson chi2) and had lower mean 1-
      (4.0 versus 7.0) and 5-minute (6.5 versus 8.4) Apgar scores (P < .01, Scheffe)
      than those in all other anesthetic groups. They also had significantly lower
      umbilical artery (UA) pH values than neonates who received nalbuphine, epidural,
      or no anesthesia (7.21 versus 7.28, 7.26, 7.29, respectively; P < .01, Scheffe).
      Factors that significantly and independently predicted intubation among all
      neonates included exposure to general anesthesia (odds ratio [OR] 4.1; 95%
      confidence interval [CI] 1.9, 8.9) and lower infant weight (OR 10.1 per kg
      decrease; CI 5.1, 20). Factors predicting UA pH at most 7.15 included
      preeclampsia (OR 3.0; CI 1.5, 5.9) and older maternal age (OR 1.3 per 5 years; CI
      1.02, 1.64); vertex delivery (OR 0.5; CI 0.2, 0.9) was protective. Factors
      predicting a 5-minute Apgar less than 7 were meconium (OR 1.5 per category going
      from none to terminal to light to heavy; CI 1.04, 2.3), general anesthesia (OR
      6.9; CI 2.6, 18.2), lower infant weight (OR 16.5 per kg decrease; CI 7.8, 34.5),
      and vaginal breech delivery (OR 7.0; CI 1.8, 28.6); cesarean delivery (OR 0.2; CI
      0.08, 0.66) was protective. Spontaneous vertex delivery raised the UA pH, and
      preeclampsia, amnioinfusion, breech delivery, and general anesthesia
      significantly and independently lowered the UA pH among all neonates. For infants
      delivered by cesarean, "fetal distress," preeclampsia, previous spontaneous
      abortion, failed forceps use, and nalbuphine significantly and independently
      predicted lower UA pH. CONCLUSION: Risk factors for poorer immediate neonatal
      outcomes among growth-restricted neonates include preeclampsia, fetal distress,
      breech delivery, forceps use, nalbuphine during labor, lower infant weight, and
      general anesthesia.

PMID- 9610996
TI  - Standards of birth weight in twin gestations stratified by placental
      chorionicity.
AB  - OBJECTIVE: To establish fetal growth nomograms for twin gestations, categorized
      by placental chorionicity, and to compare them with those of published singleton
      and twin nomograms. METHODS: Computerized data files of live births of all twins
      delivered between January 1990 and October 1996 at Saint Peter's Medical Center
      were used. Birth weight curves corresponding to the fifth, tenth, 50th, 90th, and
      95th percentiles were derived separately for twins with monochorionic and
      dichorionic placentation. We generated the curves by applying the method of
      generalized estimating equations, after adjusting for the potential intracluster
      correlation due to twinning. The curves were then smoothed on the basis of
      nonparametric restricted cubic splines to derive (smoothed) birth weight
      percentiles. We then compared our twin birth weight nomogram to six previously
      published singleton and two twin nomograms published previously for predicting
      small for gestational age infants (defined as birth weight below the tenth
      percentile). RESULTS: Among 1302 twin fetuses, 272 (21%) were monochorionic.
      Twins from monochorionic gestations weighed, on average, 66.1 g (standard
      deviation 28.4 g, P = .02) less than twins from dichorionic gestations after
      correcting for gestational age. Twin curves based on parity (nulliparity versus
      multiparity) were not different from each other. Analyses indicate that all
      previously published singleton nomograms approximate twin growth reasonably well
      between 32 and 34 weeks, but they underestimate twin growth at earlier
      gestational ages (between 25 and 32 weeks) and overestimate twin growth beyond 34
      weeks' gestation. Similarly, a comparison of previously published twin nomograms
      with those of ours indicates that the growth standards in our population were
      similar to those in other published twin nomograms. CONCLUSION: We recommend that
      future epidemiologic and clinical studies use twin nomograms to identify growth
      restricted twin fetuses. Moreover, because fetal growth is influenced by
      placental chorionicity, we recommend that fetal growth assessment in twin
      gestations consider placental chorionicity, whenever the information is
      available.

PMID- 9610997
TI  - Placental pathology in patients using cocaine: an observational study.
AB  - OBJECTIVE: Although retroplacental hemorrhage is a major cause of fetal death,
      its etiology often remains obscure. In some reports, cocaine use by pregnant
      women has been associated with retroplacental hemorrhage and clinical abruptio
      placentae. This study was designed to assess the occurrence of chorionic villus
      hemorrhage, an entity shown recently to be associated with retroplacental
      hemorrhage, in the placentas of cocaine users. METHODS: Twenty-nine placentas
      from cocaine users and 15 placentas from drug-free controls, as determined by
      questionnaire and urine toxicology screen, were examined prospectively, and
      pathological findings documented. The prevalence of retroplacental hemorrhage,
      chorionic villus hemorrhage, edema, chorioamnionitis, funisitis, infarction,
      fetal vessel thrombosis, and intervillus hemorrhage was examined in the two
      groups. RESULTS: Chorioamnionitis was the most frequent finding in both groups
      (58% of cocaine users, 66% of controls). Edema of moderate severity or greater
      was found only in the cocaine-using group (17%). The prevalence of chorionic
      villus hemorrhage among women using cocaine also was 17%. CONCLUSION: Cocaine use
      during pregnancy may be associated with chorionic villus hemorrhage and villus
      edema, even in the absence of clinical abruptio placentae. The relationship
      between abnormal placental morphology and adverse perinatal outcomes remains to
      be determined.

PMID- 9610998
TI  - Ring block for neonatal circumcision.
AB  - OBJECTIVE: To determine whether a difference in the behavioral and physiologic
      response to circumcision can be demonstrated between neonates undergoing the
      procedure with ring block and those receiving no anesthesia. METHODS: Forty
      healthy male newborns were assigned randomly to receive either ring block or no
      anesthesia. Indices of perceived pain including crying time, behavioral state,
      oxygen saturation, and heart and respiratory rates were recorded at baseline and
      at intervals during the circumcision. Infants were reassessed 2 minutes and 2
      hours postoperatively. RESULTS: Infants receiving ring block cried less than did
      controls (P < .001). Anesthetized infants had smaller increases in heart rate (P
      < .005) and demonstrated less arousal (P < .005) during each operative interval.
      For all operative intervals combined, anesthetized infants had a smaller decrease
      in oxygen saturation (P < .001) and a smaller increase in respiratory rate (P =
      .005) than did controls. Two minutes postoperatively, anesthetized infants had
      returned to their baseline behavioral state, whereas controls remained
      significantly more aroused (P < .005). Two hours postoperatively, there were no
      significant differences in any variables between the groups, nor between each
      group and its baseline. There were no complications related to anesthesia
      administration. CONCLUSION: Neonatal circumcision causes behavioral and
      physiologic changes consistent with the perception of pain. Ring block is an
      effective method of anesthesia for this procedure.

PMID- 9610999
TI  - Autonomic imbalance in preeclampsia: evidence for increased sympathetic tone in
      response to the supine-pressor test.
AB  - OBJECTIVE: To examine whether an increase in sympathetic nervous tone contributes
      to the augmented response to cardiovascular reflex testing in preeclamptic women.
      METHODS: Maternal electrocardiograms were recorded from 11 nonpregnant women and
      25 normotensive and 15 preeclamptic nulliparous women at term, during periods of
      quiet respiration in the left-lateral position and after shifting to the supine
      position. Power spectral analysis was applied to epochs of 512 consecutive beat
      to-beat intervals to determine the contribution of sympathetic tone,
      parasympathetic tone, and respiratory sinus arrhythmia to heart rate variability.
      RESULTS: Both normotensive and preeclamptic pregnant women showed a significant
      decrease in respiratory sinus arrhythmia and an increase in sympathetic tone
      compared with nonpregnant women. In nonpregnant and in normotensive pregnant
      women, shifting from the left-lateral to the supine position did not cause any
      change in autonomic characteristics. In contrast, preeclamptic women demonstrated
      a marked increase in power within the very low-frequency range representing
      sympathetic tone, from 288 +/- 214 to 556 +/- 322 second2/Hz, in response to the
      same challenge (P < .05). CONCLUSION: Third-trimester pregnancy is characterized
      by sympathetic overactivity. When complicated by preeclampsia, sympathetic
      overreactivity to cardiovascular reflex testing is observed. Our data support the
      notion that the pathophysiologic phenomena that characterize preeclampsia are
      mediated not only by circulating or locally acting vasoactive substances, but
      also, at least in part, by an increase in sympathetic nervous tone.

PMID- 9611000
TI  - Midtrimester N-terminal proatrial natriuretic peptide, free beta hCG, and alpha
      fetoprotein in predicting preeclampsia.
AB  - OBJECTIVE: To determine whether maternal midtrimester serum N-terminal peptide of
      proatrial natriuretic peptide, free beta subunit of human chorionic gonadotropin
      (hCGbeta), or alpha-fetoprotein (AFP) levels can predict preeclampsia. METHODS: A
      population-based cohort included 1037 nulliparous women, of whom 637 (61%)
      participated in a maternal serum Down syndrome screening program. Measurements of
      hCGbeta, AFP, and N-terminal peptide of proatrial natriuretic peptide were made
      from maternal serum collected at 15-19 weeks' gestation. Sensitivity,
      specificity, and predictive values were calculated for elevated AFP (at least 2.0
      multiples of the median [MoM]) and hCGbeta (at least 2.0 MoM) values. RESULTS: No
      difference was found in the concentrations of the N-terminal peptide of proatrial
      natriuretic peptide among the 30 women in whom preeclampsia developed later
      (median 270 [range 142-604] pmol/L) compared with 536 women who remained
      normotensive (274 [51-2626] pmol/L). The sensitivity and specificity of elevated
      AFP in predicting preeclampsia were 3% and 98% and those of elevated hCGbeta were
      20% and 84%, respectively. When a stepwise multiple logistic regression model was
      used, only mean arterial pressure was an independent risk factor in predicting
      preeclampsia. CONCLUSION: Determinations of the proposed new marker N-terminal
      peptide of proatrial natriuretic peptide, as well as serum hCGbeta or AFP, are
      not helpful in predicting preeclampsia.

PMID- 9611001
TI  - Interleukin-1beta and interleukin-8 concentrations in the lower uterine segment
      during parturition at term.
AB  - OBJECTIVE: To assess the roles of interleukin-1beta, interleukin-8, and
      fibroblasts in the lower uterine segment during parturition. METHODS: Lower
      uterine segment biopsy specimens were obtained from 36 women undergoing cesarean
      delivery at various stages of cervical dilation (less than 2 cm, n = 8; 2 to less
      than 4 cm, n = 9; 4-6 cm, n = 10; more than 6 cm, n = 9). The concentrations of
      interleukin-1beta and interleukin-8 in protein extracts prepared from the tissue
      samples were measured by enzyme immunoassays. The effect of incubation with
      interleukin-1beta (30 U/mL) on interleukin-8 secretion by lower uterine segment
      fibroblasts in vitro also was determined. RESULTS: The median interleukin-1beta
      concentration in the specimens increased from 1.3 pg/mg of total protein at less
      than 2 cm of dilation to 22.2 pg/mg of total protein at 4-6 cm of dilation (P <
      .05). No further increase was detectable after 6 cm of dilation. The interleukin
      8 concentration increased from 17.2 pg/mg of total protein at less than 2 cm of
      dilation to 2080.7 pg/mg of total protein at 4-6 cm of dilation (P < .05), thus
      paralleling the increase in interleukin-1beta concentration. Interleukin-1beta
      induced a significant increase in interleukin-8 secretion by fibroblasts in
      vitro, from 0.8 ng/10(6) cells to 35.6 ng/10(6) cells. CONCLUSION: The increase
      in interleukin-8 concentration in the lower uterine segment during parturition
      may be induced by interleukin-1beta and fibroblasts may be one of the sources of
      this interleukin-8.

PMID- 9611002
TI  - Placental mitochondrial DNA and respiratory chain enzymes in the etiology of
      preeclampsia.
AB  - OBJECTIVE: To evaluate the occurrence of the most common mutations and deletions
      in mitochondrial DNA and deficiencies in the enzyme complexes of the
      mitochondrial respiratory chain in placentas from preeclamptic women. METHODS:
      Mitochondria were isolated from the placentas of 17 preeclamptic or 25 control
      women, and the activities of mitochondrial respiratory chain complexes were
      measured. Deletions and three common point mutations of mitochondrial DNA were
      searched for by the Southern blot and polymerase chain reaction (PCR) methods
      from the same placentas. RESULTS: Mean (+/- standard deviation) mitochondrial
      respiratory chain enzyme complex activities in placentas on protein basis
      (nmol/min/mg of protein) were similar in preeclamptics and controls (nicotinamide
      adenine dinucleotide, reduced form-ubiquinone oxidoreductase 25.84 +/- 9.29
      versus 31.02 +/- 7.52; nicotinamide adenine dinucleotide, reduced form-cytochrome
      c oxidoreductase 77.88 +/- 42.24 versus 104.06 +/- 56.73; succinate-cytochrome-c
      oxidoreductase 57.90 +/- 13.83 versus 64.44 +/- 20.16; cytochrome-c oxidase
      106.43 +/- 35.46 versus 128.37 +/- 48.64, respectively) and they were similar
      also when referenced to the mitochondrial marker enzyme citrate synthase. The
      sample sizes in both patient and control groups were found to be large enough by
      post hoc test. Large-scale deletions or the common 5-kb and 7.4-kb deletions were
      not detected, even at the sensitivity level of PCR. The three most common point
      mutations were not found in either control or preeclamptic placental samples.
      CONCLUSION: Common mitochondrial DNA mutations seem to play no major role in the
      universal etiology of preeclampsia, as assessed by analysis of the mitochondrial
      genome and respiratory chain enzyme activities in vitro. This does not exclude
      possible alterations in the energy state of the preeclamptic placenta.

PMID- 9611003
TI  - The effect of fetal intravascular blood transfusion on plasma endothelin levels
      in fetuses with rhesus alloimmunization.
AB  - OBJECTIVE: To determine if intrauterine intravascular fetal transfusion affects
      fetal umbilical venous endothelin levels. METHODS: Endothelin concentrations were
      measured by radioimmunoassay in fetal umbilical venous blood obtained immediately
      before and after 36 fetal transfusions performed for Rh alloimmune hemolytic
      anemia. Umbilical venous pressures also were recorded before and after
      transfusion. RESULTS: The mean (+/- standard deviation [SD]) gestational age at
      transfusion was 27.0 +/- 4.6 weeks, whereas the initial and post-transfusion
      hematocrits were 23.3 +/- 8.5% and 41.8 +/- 6.3%, respectively. Post-transfusion
      endothelin levels correlated significantly with the volume of transfused blood (r
      = .41; P = .03) and with post-transfusion increases in umbilical vein pressure (r
      = .86; P < .001). Among fetuses undergoing initial transfusion, there were
      significant differences between mean (+/- SD) pre- and post-transfusion
      endothelin levels [3.6 (+/- 2.2) pg/mL versus 6.3 (+/- 4.0) pg/mL, respectively;
      P = .02]. In contrast, among fetuses undergoing a repeat fetal transfusion, no
      differences in mean (+/- SD) pre- versus post-transfusion endothelin levels were
      observed [3.8 (+/- 1.8) pg/mL versus 2.2 (+/- 1.77) pg/mL, respectively; P =
      .3)]. Step-wise multiple regression analysis identified order of transfusion as a
      significant predictor of change in endothelin levels from pre- to post
      transfusion measurements (adjusted r2 = .26; P = .003). CONCLUSION: Rapid
      expansion of fetal intravascular volume by intravenous transfusion of packed red
      blood cells with a high hematocrit enhances fetal endothelin levels in those
      fetuses undergoing initial but not subsequent transfusions.

PMID- 9611004
TI  - Comparison of pelvic organ prolapse in the dorsal lithotomy compared with the
      standing position.
AB  - OBJECTIVE: To determine if there is a significant difference in the degree of
      pelvic organ prolapse assigned during examination in the standing position
      compared with the dorsal lithotomy position with the patient performing maximal
      Valsalva maneuver. METHODS: Fifty-one women with symptoms of pelvic organ
      prolapse were examined in both the dorsal lithotomy position, while performing
      maximal Valsalva, and in the standing position at the same visit by one of two
      examiners. Nine site-specific measures and summary stages were recorded, as
      outlined by the International Continence Society's classification system for
      pelvic organ prolapse. The data were analyzed by Wilcoxon signed-rank test and
      correlation coefficients. RESULTS: The mean age was 52 +/- 15 years. Excellent
      correlation was noted between all six points representing the vaginal prolapse.
      The R values for point Aa were 0.97, Ba 0.96, C 0.98, Ap 0.97, Bp 0.96, and D
      0.97. The total vaginal length, perineal body, and genital hiatus measurements
      were performed in the dorsal lithotomy position with the patient at rest and were
      not repeated. The stages were identical in 48 of 51 patients. The average stage
      in the dorsal lithotomy position was 2.3 and in the standing position, 2.3. There
      was no statistically significant difference between the stage or any of the
      measured points in the dorsal lithotomy and standing examinations. CONCLUSION:
      The degree of pelvic organ prolapse can be assessed adequately in the dorsal
      lithotomy position with the patient performing maximal Valsalva. It is not
      necessary to routinely repeat the examination in the standing position.

PMID- 9611005
TI  - Stress incontinence diagnosed without multichannel urodynamic studies.
AB  - OBJECTIVE: To determine if the clinical diagnosis of stress urinary incontinence
      made on the basis of simple criteria correlates with the diagnosis of genuine
      stress incontinence as determined by provocative multichannel urodynamic testing.
      METHODS: The charts of 652 women who presented for clinical evaluation of a
      variety of lower urinary tract complaints were reviewed if they met all of the
      following criteria: 1) a predominant complaint of stress incontinence, 2)
      positive cough stress-test results, 3) postvoid residual urine volume no more
      than 50 mL, 4) a functional bladder capacity of at least 400 mL as determined by
      a completed 24-hour frequency-volume chart, and 5) a full multichannel urodynamic
      evaluation. Seventy-four patients met all these criteria. The clinical diagnosis
      of stress incontinence was based on the presence of factors 1-4; this diagnosis
      then was compared with the results of provocative multichannel urodynamic
      testing. RESULTS: Genuine stress incontinence was confirmed in 72 (97%) of 74
      patients meeting the aforementioned clinical criteria. In one patient, detrusor
      instability alone was demonstrated during urodynamic testing. In 11 patients with
      genuine stress incontinence (15%), an element of detrusor instability was also
      present at the time of urodynamic testing. One patient had normal urodynamic
      study findings, with no incontinence demonstrated. CONCLUSION: Rigorously defined
      clinical criteria are highly reliable in predicting the presence of genuine
      stress incontinence at the time of urodynamic testing. Because of the potential
      implications of this finding for clinical practice, further investigation is
      warranted.

PMID- 9611006
TI  - Intraepithelial and invasive squamous cell neoplasia of the vulva: trends in
      incidence, recurrence, and survival rate in Norway.
AB  - OBJECTIVE: To characterize time trends in incidence of intraepithelial and
      invasive vulvar neoplasia, transition of intraepithelial vulvar neoplasia to
      invasive cancer, and survival rate based on a total population. METHODS: The
      Cancer Registry of Norway was used to identify all Norwegian inhabitants
      diagnosed during 1956-1990 with squamous cell carcinoma of the vulva, and all
      those with intraepithelial vulvar neoplasia diagnosed during 1973-92. RESULTS:
      The incidence rate of intraepithelial neoplasia increased three-fold from 1973-77
      to 1988-92, and 3.4% changed into invasive disease. Multivariate analyses
      identified age as a significant variable. The age-adjusted incidence rate for
      squamous cell carcinoma was constant for the whole period. The ratio between
      recurrence and the total number of invasive cancer varied from 21% to 31%. The 5
      year survival rates have not changed significantly over the period. Age was
      revealed as a strong prognostic factor, showing an excess death rate by
      increasing age. CONCLUSION: The incidence of vulvar intraepithelial neoplasia has
      increased substantially over the last 40 years, but that of invasive vulvar
      cancer has not changed appreciably.

PMID- 9611007
TI  - Where's the high-grade cervical neoplasia? The importance of minimally abnormal
      Papanicolaou diagnoses.
AB  - OBJECTIVE: To characterize the relative contributions of the different abnormal
      Papanicolaou smear cytologic diagnoses in the Bethesda System to the subsequent
      histologic diagnosis of high-grade cervical neoplasia. METHODS: A total of 46,009
      nonpregnant female members of the Kaiser Permanente Health Plan, Northern
      California Region, were studied prospectively. The main outcome measures included
      routine Papanicolaou smear diagnoses and subsequent histologic diagnosis of
      colposcopically directed cervical tissue specimens. RESULTS: Atypical squamous
      cells of undetermined significance (ASCUS) was the most common abnormal
      Papanicolaou diagnosis, representing 3.6% of the total number of smears. Of the
      total number of cases of histologically confirmed high-grade cervical neoplasia
      present in the population, the largest proportion (38.8%) was in women with
      smears showing ASCUS. Minimal abnormalities combined (ASCUS, atypical glandular
      cells of undetermined significance, and low-grade squamous intraepithelial
      lesion) were coincident with 68.6% of the cases of histologic high-grade cervical
      neoplasia diagnosed in this routine screening population. CONCLUSION: Recognition
      of the importance of equivocal and mild Papanicolaou test abnormalities in the
      subsequent diagnosis of high-grade cervical neoplasia emphasizes the need for
      accurate and cost-effective triage of the large population of women with
      minimally abnormal Papanicolaou diagnoses.

PMID- 9611008
TI  - Adjuvant chemotherapy after radical hysterectomy for cervical carcinoma: a
      comparison with effects of adjuvant radiotherapy.
AB  - OBJECTIVE: To compare the efficacy of adjuvant chemotherapy after radical
      hysterectomy with that of adjuvant radiotherapy. METHODS: One hundred one women
      with invasive cervical carcinoma (stage IB through early stage IIB) underwent
      radical hysterectomy at Saga Medical School Hospital. Of these patients, 53 with
      squamous or adenosquamous carcinoma were classified as high risk, based on the
      presence of one or more of the following high-risk factors for recurrence: 1)
      lymph node metastasis, 2) deep cervical stromal invasion (greater than 3/4
      thickness), and 3) parametrial invasion. Adjuvant chemotherapy with a combination
      of cis-diamminedichloroplatinum (CDDP), vincristine, mitomycin C, and peplomycin
      (POMP), was prescribed. The outcome was compared with that for 127 patients who
      were classified as high risk under the same criteria and who received adjuvant
      radiotherapy at Kyushu University Hospital. RESULTS: The 5-year survival rates
      were much the same: 83.0% for adjuvant chemotherapy and 81.7% for adjuvant
      radiotherapy. In the chemotherapy group, intra- and extrapelvic recurrences
      accounted for 85 and 23% of all recurrences, respectively, whereas recurrences
      were noted for 38 and 71% in the radiotherapy group, respectively (P < .01).
      CONCLUSION: The use of adjuvant chemotherapy reduces extrapelvic recurrences. The
      combination of both adjuvant therapies may improve the prognosis for high-risk
      patients.

PMID- 9611009
TI  - Carotid artery wall changes in estrogen-treated and -untreated postmenopausal
      women.
AB  - OBJECTIVE: To investigate whether the thickness of the layers of the carotid
      artery (externa, media, and intima) are affected by menopause and its treatment
      with hormone replacement therapy (HRT). METHODS: One hundred twenty-nine
      postmenopausal women were recruited sequentially and classified into three
      groups. Forty-six were taking oral HRT, 32 had estradiol implants, and 51 had
      never taken HRT. The three layers of the externa wall of the carotid artery were
      identified and measured by high-resolution ultrasound. RESULTS: Women with
      implants had thicker carotid artery wall measurements (0.84 +/- 0.26 mm) than the
      other groups. The media (0.32 +/- 0.11 mm) was significantly thicker in the
      implant group. This layer has a high connective tissue component, including
      collagen type I, collagen type III, and elastin fibers. The intima layer was
      thinner (0.25 +/- 0.09 mm) in the oral HRT group compared with controls (0.29 +/-
      0.1 mm). A statistically significant higher intima-media ratio (1.17 +/- 0.05)
      was calculated for the control group, compared with both the oral HRT (0.92 +/-
      0.04) and implant groups (0.94 +/- 0.03). CONCLUSION: Our findings suggest that
      HRT given to postmenopausal women influences differentially the layers of the
      carotid artery. Hormones seem to encourage thickening of the layers with the
      highest connective tissue component (externa and media) and to delay thickening
      of the atheromatous intima layer. These effects on the vascular system may be
      partly responsible for the cardioprotection attributed to HRT.

PMID- 9611010
TI  - Leukocytes in the cervix: a quantitative evaluation of cervicitis.
AB  - OBJECTIVE: To quantify the numbers of leukocytes in the normal cervix and relate
      these numbers to the diagnosis of cervicitis. METHODS: Isolated cell suspensions
      were prepared from cervical tissue recovered at hysterectomy from 37 women who
      had no obvious cervical disease. The percentages of CD45+ cells (leukocytes) in
      these preparations were determined using immunofluorescence-based flow cytometric
      analysis. These percentages were compared with the pathologist's assessment of
      cervicitis. RESULTS: Leukocytes were present in all cervical samples tested. For
      endocervical samples, the mean (+/- standard error of the mean [SEM]) percentage
      of CD45+ cells was 12.4 +/- 1.9% of cells in patients with a diagnosis of
      cervicitis (n = 16) and 9.1 +/- 1.1% in patients without cervicitis (n = 17). For
      ectocervical samples, the mean (+/- SEM) percentage was 14.8 +/- 3.0% in those
      with cervicitis (n = 16) and 9.5 +/- 1.6% in those without cervicitis (n = 19).
      The differences between samples from patients with cervicitis and those without
      cervicitis were not statistically significant at the .05 level. Intra- and
      interassay variabilities were 5.7 +/- 1.2% and 7.3 +/- 1.6%, respectively.
      CONCLUSION: Our study demonstrates there is a resident population of leukocytes
      in the cervix. Leukocyte number did not relate clearly and consistently to the
      diagnosis of cervicitis made by the pathologist. We suggest that the resident
      population of leukocytes, in the absence of other indicators of infection, may
      confuse determinations of cervicitis.

PMID- 9611011
TI  - Vaginal douching as a risk factor for cervical Chlamydia trachomatis infection.
AB  - OBJECTIVE: To evaluate the association between vaginal douching and cervical
      Chlamydia trachomatis infection. METHODS: We analyzed cross-sectional data from a
      study conducted at Group Health Cooperative of Puget Sound, a nonprofit health
      maintenance organization in western Washington state. Participants were
      nonpregnant women Group Health enrollees between the ages of 18 and 34 years who
      were attending two primary care clinics either for nonurgent visits, primarily
      routine preventive health visits, or in response to an invitation from the study.
      Before the clinical examination, all completed a self-administered survey
      assessing demographic and behavioral characteristics, including the timing,
      frequency, products used, and reasons for douching. Chlamydial infection was
      ascertained via cell culture isolation of C trachomatis from endocervical
      specimens obtained at the same visit. RESULTS: Chlamydia trachomatis was isolated
      from cervical cultures in 58 (3.4%) of 1692 study participants. Women who
      reported douching in the 12 months before their clinic visit had an increased
      likelihood of chlamydial infection compared with women who did not douche
      (prevalence odds ratio [OR] 2.29, 95% confidence interval [CI] 1.22, 4.30, after
      adjusting for confounding factors). The likelihood was higher for women who
      reported douching more often: OR 2.60 (95% CI 1.29, 5.24) for women who douched
      one to three times per month, and OR 3.84 (95% CI 1.26, 11.70) for those douching
      four times or more per month. These associations were slightly stronger when
      women who reported douching because of an infection were excluded from the
      analysis. CONCLUSION: These results support the hypothesis that vaginal douching
      predisposes to acquisition of cervical chlamydial infection and are compatible
      with previous studies that report associations between douching and sequelae of
      chlamydial infection, including pelvic inflammatory disease, ectopic pregnancy,
      and infertility.

PMID- 9611012
TI  - Sciatic hernia as a cause of chronic pelvic pain in women.
AB  - OBJECTIVE: To review experience with 20 women treated for sciatic hernia between
      1993 and 1997. METHODS: Patients with chronic pelvic pain and sciatic hernias,
      identified retrospectively from chart review, were seen during a 46-month period
      that covered the surgical experience at our institution and included
      approximately 1100 cases. The median length of follow-up was 13 months (range 3
      36). RESULTS: Sciatic hernia was diagnosed in 20 white women with chronic pelvic
      pain and was treated using laparoscopy. In 14 cases the hernias were right sided,
      in five they were left sided, and in one they were bilateral. All sciatic hernias
      contained the ipsilateral ovary alone or with its fallopian tube. All 20 patients
      reported symptomatic relief at follow-up. CONCLUSION: Sciatic hernia is a cause
      of chronic pelvic pain and should be considered in the differential diagnosis.

PMID- 9611013
TI  - The prevalence of domestic violence among women seeking abortion.
AB  - OBJECTIVE: To determine the prevalence of self-reported abuse in a population of
      women aged 18 years or older seeking elective pregnancy termination, and to
      compare abused and nonabused women with respect to the primary reasons for
      pregnancy termination. METHODS: A self-administered questionnaire was returned by
      486 women seeking outpatient abortion. The survey included demographic
      information, abuse screening, and items regarding partner involvement/awareness
      of the pregnancy, and abuse as a determinant of the abortion decision. One open
      ended item asking the primary reason for pregnancy termination was included.
      RESULTS: The prevalence of self-reported abuse in this population was 39.5%.
      White women were significantly more likely to report any history of abuse than
      nonwhite women. Relationship issues were the only reason for pregnancy
      termination given more often by women with an abuse history than by nonabused
      women. Women with abuse histories were significantly less likely than nonabused
      women to inform the partner of the pregnancy or to have partner support for or
      involvement in the abortion decision. CONCLUSION: The prevalence of abuse
      reported by women in this population suggests that many women seeking abortion
      services may have abuse histories. Abused women may have different reasons for
      pregnancy termination than nonabused women and may be more likely to make the
      abortion decision without partner involvement. When routine screening for abuse
      is included in abortion counseling, health providers have the opportunity for
      developing a safety plan and initiating appropriate referral.

PMID- 9611014
TI  - Visits to emergency departments for gynecologic disorders in the United States,
      1992-1994.
AB  - OBJECTIVE: To assess rates of visits to emergency departments for gynecologic
      disorders among women of reproductive age in the United States. METHODS: Data
      from the National Hospital Ambulatory Medical Care Survey for 1992-1994 were
      analyzed to determine rates of visits to emergency departments among women, ages
      15-44 years. Average annual rates per 1000 women were calculated using age, race,
      and region-specific population estimates. Rate ratios were used to compare rates
      among subgroups. RESULTS: Approximately 1.4 million gynecologic visits were made
      to emergency departments annually, for an average annual rate of 24.3 visits per
      1000 women, ages 15-44 years (95% confidence interval [CI] 22.0, 26.6). The most
      frequent diagnoses were pelvic inflammatory disease (average annual rate 5.8, 95%
      CI 5.0, 6.6), lower genital tract infections including sexually transmitted
      diseases (average annual rate 5.7, 95% CI 4.8, 6.6), and menstrual disorders
      (average annual rate 2.9, 95% CI 2.3, 3.5). Nearly half of all gynecologic visits
      resulted in diagnoses of genital tract infections. Younger women (ages 15-24
      years) were 2.3 (95% CI 2.0, 2.6) times as likely as older women (ages 25-44
      years), and black women were 3.6 (95% CI 2.9, 4.3) times as likely as white
      women, to visit emergency departments for gynecologic disorders. Rate ratios for
      genital tract infections were 10-20 times higher for younger black women than for
      older, white women. CONCLUSION: Almost half of gynecologic visits to emergency
      departments were related to genital tract infections, which largely are
      preventable.

PMID- 9611015
TI  - Effect of departmental policies on cesarean delivery rates: a community hospital
      experience.
AB  - OBJECTIVE: During 1994, our department adopted several strategies in an attempt
      to decrease our cesarean delivery rates. This study evaluates the effect of these
      changes on our cesarean delivery rates. METHODS: We studied data of women who
      delivered at our community hospital obstetric unit over a period of 6 years, from
      January 1, 1991, to December 31, 1996. During 1994, our department adopted labor
      management and cesarean delivery guidelines, with review of every cesarean
      delivery that did not meet guidelines and confidential individual feedback;
      established 24-hour in-house coverage; and attempted to achieve the goal of an
      annual cesarean delivery rate of less than 15%. These data were evaluated by chi2
      analysis. Women who delivered in the first 3 years (group A) were compared with
      those who delivered in the second 3 years (group B) (ie, when the changes
      occurred). P < .05 was considered significant. RESULTS: Groups A and B shared
      similar demographic characteristics. The total cesarean delivery rate decreased
      from 22.5% (group A) to 18.6% (group B) (P = .001), whereas the primary cesarean
      delivery rate decreased from 13.5% to 10.6% (P = .001) and the repeat cesarean
      delivery rate decreased from 9.0% to 7.9% (P = .03). The proportion of women who
      received oxytocin and regional anesthesia and underwent vacuum-assisted
      deliveries increased (P < .001), whereas perinatal mortality and morbidity did
      not change. CONCLUSION: The cesarean delivery rate safely decreased. These data
      suggest the importance of the commitment of attending physicians to a lower
      cesarean delivery rate, of service improvements, and of detailed feedback.

PMID- 9611016
TI  - Double pessary use in grade 4 uterine and vaginal prolapse.
AB  - BACKGROUND: Certain situations dictate conservative management of grade 4 uterine
      or vaginal vault prolapse in women. The reduction of a prolapse may not be
      possible if the vagina cannot retain a single pessary. We have used double
      pessaries in the management of this condition. TECHNIQUE: With the patient in the
      dorsal lithotomy position, either a Donut or Inflatoball (Milex Products Inc.,
      Chicago, IL) pessary is inserted and pushed into the vagina as far as is
      comfortable. A second pessary, either a flexible Gellhorn or Shaatz (Milex
      Products Inc.), then is placed caudad to the first. EXPERIENCE: We have used this
      approach in five women who have been followed for 7-15 months. There have been no
      erosions or vaginitis and all the women experienced symptomatic relief.
      CONCLUSION: In women who want or require conservative management of grade 4
      prolapse and are unable to retain a single pessary, the placement of two
      pessaries often will be successful.

PMID- 9611017
TI  - Predictors of performance on the National Board of Medical Examiners obstetrics
      and gynecology subject examination.
AB  - OBJECTIVE: To examine the correlation among the National Board of Medical
      Examiners subject examination, the US Medical Licensure Examination step 1
      scores, and grade point average and to determine if poor performance could be
      predicted by the US Medical Licensure Examination step 1 score and grade point
      average. METHODS: The subject examination scores of 148 third-year medical
      students were compared with their US Medical Licensure Examination step 1 scores
      and grade point averages. Scores below the 20th percentile were defined as poor
      performance. RESULTS: There was a significant correlation between the US Medical
      Licensure Examination score and the subject examination score (r = .6, P < .001).
      The correlation with grade point average was also significant (r = .57, P <
      .001). CONCLUSION: The US Medical Licensure Examination step 1 performance, grade
      point average, and performance on the subject examination are all correlated.
      However, use of the US Medical Licensure Examination step 1 scores and grade
      point averages to identify all students at risk was associated with a high false
      positive rate at our institution.

PMID- 9611018
TI  - Factors affecting fellowship satisfaction, thesis completion, and career
      direction among maternal-fetal medicine fellows.
AB  - OBJECTIVE: To determine fellowship satisfaction through a survey of maternal
      fetal medicine fellows. METHODS: We constructed a survey using multiple choice,
      Likert scale, ordinal, and categorical scale questions. The questions focused on
      faculty involvement, mentorship, research time and productivity, education,
      fellowship selection, ultimate goals of fellows, and satisfaction. We sent the
      survey in two mailings to all maternal-fetal medicine fellows during April and
      May 1996. RESULTS: One hundred thirty-eight surveys were mailed, and 136 were
      returned (98.5% return rate). Twenty-seven percent of fellows did not believe
      they would complete their thesis by the end of their fellowship. No statistically
      significant relationship was noted between the fellows' predicted thesis
      completion and the availability of funding, support for statistical analysis, the
      presence of animal research facilities, age, number of dependents, or year of
      fellowship. The presence of a mentor on the maternal-fetal medicine faculty
      increased the likelihood of thesis completion from 52.3% to 83.5% (P < .001).
      Similarly, the presence of a faculty advisor increased the likelihood of thesis
      completion from 58.9% to 83.5% (P = .001). Thirty-two percent of the respondents
      did not have a mentor on the faculty, and 41% did not have a faculty advisor.
      Forty percent indicated that they were too involved in clinical pursuits to
      perform research. This group was significantly more likely to believe that their
      theses would not be completed (63% versus 80%, P = .029). Overall, 22% of the
      fellows would not recommend their fellowships. Fellows with a mentor (88.2%
      versus 55.8%; P < .001) or faculty advisor (87.3% versus 64.9%; P = .002) were
      more likely than those without to recommend their fellowship. CONCLUSION: A
      mentor or faculty advisor plays a significant role in the training of maternal
      fetal medicine fellows and is associated with a higher incidence of satisfaction
      with the fellowship program, thesis completion, and entrance into academic
      practice.

PMID- 9611019
TI  - Preventing neural tube defects: the importance of periconceptional folic acid
      supplements.
AB  - OBJECTIVE: To inform the obstetrician-gynecologist of recent scientific evidence
      regarding the use of supplemental folic acid for prevention of neural tube
      defects (NTDs). DATA SOURCES: We selected English language articles via MEDLINE
      published from January 1990 through February 1997, using the search terms "folic
      acid" and "neural tube defect." Additional sources were identified through cross
      referencing and through searching selected journals published from March through
      October 1997. METHODS OF STUDY SELECTION: Articles were selected on the basis of
      their relevance to the relationship between folate intake and NTD incidence,
      mechanisms of folate responsive NTD formation, and folate provision strategy. We
      referenced 55 papers in total. TABULATION, INTEGRATION, AND RESULTS: The majority
      of evidence demonstrates a decreased incidence of NTDs with increased folic acid
      consumption. The most convincing trials were performed in Europe among women who
      were planning pregnancy by using multivitamin or folic acid supplements. Some
      studies suggest that the protective effect of folate is explained, in many cases,
      not through correction of dietary deficiencies, but through correction of
      metabolic defects. Other evidence implies that it reduces NTDs by causing
      abortion of affected conceptuses. Supplemental folic acid tablets are the most
      proven means of improving an individual's folate status, but ensuring compliance
      with a strategy using vitamin tablets is problematic. CONCLUSION: Women of
      reproductive age should be advised to take multivitamin supplements containing
      0.4 mg folic acid daily. Women with previously affected offspring who intend to
      become pregnant should take daily supplementation containing 4 mg of folic acid
      in the periconceptional period to reduce the risk of recurrence.

PMID- 9611020
TI  - Anion gap determination in preeclampsia.

PMID- 9611021
TI  - A single constant in a world of change.

PMID- 9611023
TI  - Postoperative drains at the donor sites of iliac-crest bone grafts. A
      prospective, randomized study of morbidity at the donor site in patients who had
      a traumatic injury of the spine.
AB  - A prospective, randomized study was performed to assess the effectiveness of
      postoperative closed suction drainage. One hundred and twelve consecutive
      procedures involving autologous iliac-crest bone graft were performed, from
      December 29, 1992, to July 1, 1993, following a traumatic injury of the spine in
      108 patients. Sixty of the sites from which the bone graft had been obtained were
      drained with a single large Hemovac device. The drains were maintained for two to
      five days postoperatively. The remaining fifty-two incisions were closed without
      a drainage device. All patients were evaluated clinically for problems with wound
      healing. The incisions were considered to be healed when they had been
      asymptomatic for one year. Of eleven patients who had problems with wound
      healing, six had been managed with a drain and five had not. The findings of this
      study do not support the routine use of drainage at the donor sites of iliac
      crest bone grafts.

PMID- 9611022
TI  - Use of an intramedullary hip-screw compared with a compression hip-screw with a
      plate for intertrochanteric femoral fractures. A prospective, randomized study of
      one hundred patients.
AB  - One hundred elderly patients who had an intertrochanteric femoral fracture were
      randomized to treatment with a compression hip-screw with a plate (fifty
      patients) or a new intramedullary device, the intramedullary hip-screw (fifty
      patients). All patients were followed prospectively for one year or until death.
      A detailed assessment of the functional status and the plain radiographs of the
      hip was performed one, three, six, and twelve months postoperatively. The two
      treatment groups were strictly comparable. The operative time needed to insert
      the intramedullary hip-screw was significantly greater than that needed to insert
      the compression hip-screw with the plate (p = 0.02), but use of the
      intramedullary hip-screw was associated with less estimated intraoperative blood
      loss (p = 0.011). The prevalence of perioperative complications, such as
      bronchopneumonia, cardiac failure, and urinary tract infection, was comparable in
      the two treatment groups. There were one intraoperative fracture of the femoral
      shaft and two intraoperative fractures of the greater trochanter in the group
      managed with the intramedullary hip-screw. One patient had pulling-out of the
      compression hip-screw on the seventh postoperative day. Four patients had a
      trochanteric wound hematoma, without infection, after insertion of an
      intramedullary hip-screw. All but one of the fractures healed. The one non-union,
      which was in a patient who had a compression hip-screw, was treated with a
      hemiarthroplasty. The mortality rate was similar in the two treatment groups. The
      patients who had an intramedullary hip-screw had, on the average, significantly
      better mobility at one (p < 0.0001) and three months (p = 0.0013)
      postoperatively. This difference was no longer seen at six and twelve months,
      although the patients who had an intramedullary hip-screw still had significantly
      better walking ability outside the home at those time-periods (p = 0.05). The
      compression hip-screw was removed from two patients because of pain in the mid
      portion of the thigh, which had begun after consolidation of the fracture.
      Fourteen patients who had an intramedullary hip-screw had cortical hypertrophy at
      the level of the tip of the nail at twelve months postoperatively. Cortical
      hypertrophy was significantly related to the use of two interlocking screws (p =
      0.02). Six of these patients also had pain in the mid-portion of the thigh, and
      the nail had been locked with two screws in five of them. Three of the six
      patients had the hardware removed because of the pain, and the symptoms resolved.
      A seventh patient had pain without cortical hypertrophy. The intramedullary hip
      screw device was associated with significantly less sliding of the lag-screw and
      subsequent shortening of the limb in the region of the thigh (p = 0.012 and
      0.019, respectively); these differences were more pronounced when the unstable
      fractures in the two treatment groups were compared (p < 0.001).

PMID- 9611024
TI  - Prosthetic knee replacement after resection of a malignant tumor of the distal
      part of the femur. Medium to long-term results.
AB  - We evaluated the medium to long-term results of treatment with a custom
      prosthetic knee replacement after wide resection of a primary malignant tumor of
      the distal part of the femur in forty consecutive patients. The duration of
      follow-up ranged from five to seventeen years (median, eight years). At the time
      of the latest follow-up, thirty-five (88 per cent) of the forty patients were
      free of disease and five (13 per cent) were alive with metastatic disease. No
      local recurrence was observed. Twenty early complications occurred in eighteen
      patients (45 per cent). Aseptic loosening of the femoral component, which
      necessitated a revision in eleven patients at an average of fifty-one months, was
      the most frequent mode of failure. The rate of prosthetic survival, as estimated
      with use of the Kaplan-Meier method, was 85, 67, and 48 per cent at three, five,
      and ten years. Univariate analysis demonstrated that the rate of prosthetic
      survival was significantly worse for male patients, for those in whom at least 40
      per cent of the femur had been resected, for those who had had total resection of
      the quadriceps muscles or subtotal resection (preservation of only the rectus
      femoris muscle), and for those in whom a straight femoral stem had been used (p <
      0.05 for all comparisons). Multivariate analysis showed that the independent
      adverse prognostic factors for prosthetic survival were male gender, resection of
      at least 40 per cent of the femur, and fixation of the femoral stem with cement.
      The rate of limb salvage was calculated, with use of the Kaplan-Meier method, to
      be 93 per cent at three years and 90 per cent at five and ten years. At the
      latest follow-up examination, the functional scores according to the
      classification system of the Musculoskeletal Tumor Society ranged from 14 to 29
      points; the mean was 24 points, which represents function that is 80 per cent
      that of normal. The mean scores in the categories of walking supports and gait
      were better for the patients in whom the quadriceps muscles had been preserved
      than for those who had had total or subtotal resection of those muscles. Although
      advances in imaging and local therapy narrow the indications for an extra
      articular resection of a tumor, the implant that was used in the present study
      continues to be used in approximately 15 per cent of patients who have a fracture
      or an intra-articular extension of the tumor that necessitates extensive extra
      articular resection.

PMID- 9611025
TI  - Fibrous dysplasia of the proximal part of the femur. Long-term results of
      curettage and bone-grafting and mechanical realignment.
AB  - We reviewed the long-term outcomes of treatment of fibrous dysplasia of the
      proximal part of the femur in twenty-two patients (twenty-seven femora). There
      were fifteen male patients and seven female patients. Patients who had monostotic
      disease had no involvement of the calcar femorale, fewer microfractures, less
      deformity, and stronger bone that could support internal fixation. Patients who
      had polyostotic disease had frequent involvement of the calcar femorale; more
      microfractures; severe deformity, including shepherd's crook deformity; and, in
      many instances, bone that could not support internal fixation. Twenty-two of the
      twenty-seven femora had a microfracture at the time of the initial presentation.
      At least one osteotomy was performed in four femora that had monostotic disease
      and in nine femora that had polyostotic disease. Curettage and cancellous or
      cortical bone-grafting did not appear to have any advantage compared with
      osteotomy alone in the treatment of symptomatic lesions, as all grafts resorbed
      with persistence of the lesion. At the time of the latest follow-up evaluation,
      no lesion had been eradicated or had decreased in size. A satisfactory clinical
      result was achieved in twenty patients (twenty-four femora): nine who had
      monostotic disease and eleven who had polyostotic disease. Two patients who had
      polyostotic disease and an endocrinopathy (one of whom had bilateral involvement)
      had an unsatisfactory result. All three femora in these two patients had a neck
      shaft angle of less than 90 degrees at the time of the most recent follow-up
      evaluation. Varus deformity of the proximal part of the femur is best treated
      with valgus osteotomy and internal fixation early in the course of the disease.
      If the calcar of the femoral neck is involved or if the quality of the bone is
      such that internal fixation is not possible, a medial displacement valgus
      osteotomy can provide a more mechanically favorable position for healing of the
      microfracture.

PMID- 9611026
TI  - Glenoid deformity secondary to brachial plexus birth palsy.
AB  - The association between internal rotation contracture secondary to brachial
      plexus birth palsy and deformity and posterior dislocation of the glenohumeral
      joint has been known for a long time. The precise nature of these deformities and
      their pathogenesis, however, remain unclear. Twenty-five children, ranging in age
      from 1.5 to 13.5 years, had an operation to release an internal rotation
      contracture secondary to brachial plexus birth palsy; eleven had a latissimus
      dorsi transfer to augment external rotation power as well. Arthrograms were made
      intraoperatively in order to clarify the pathological changes that occur in the
      glenohumeral joint during growth in patients who have this condition. Seven
      children had a concentric glenohumeral joint (the humeral head was well centered
      in the glenoid fossa). The remaining eighteen children (72 per cent) had a
      deformity of the posterior aspect of the glenoid. Five of these children had
      flattening of the posterior aspect of the glenoid, seven had a biconcave glenoid
      with the humeral head articulating with the posterior of the two concavities, and
      six had a so-called pseudoglenoid (the most severe deformity, in which the
      humeral head articulated with a distinct, retroverted, posterior articular
      surface). Internal rotation contracture secondary to brachial plexus birth palsy
      may lead to glenoid deformity that is severely advanced by the time that the
      child is two years old. In patients who have such a contracture, we recommend
      early imaging of the shoulder with arthrography or some other modality to allow
      visualization of the skeletally immature glenohumeral joint.

PMID- 9611027
TI  - Glenohumeral deformity secondary to brachial plexus birth palsy.
AB  - Ninety-four patients who had brachial plexus birth palsy were entered into a
      prospective study to evaluate the association between persistent palsy, age
      related musculoskeletal deformity, and functional limitations. Of these patients,
      forty-two had either computerized tomography or magnetic resonance imaging to
      assess the presence and degree of incongruity of the glenohumeral joint,
      deformity of the humeral head, and hypoplasia of the glenoid as part of the
      preoperative planning for a reconstructive operation. Functional ability was
      rated with use of the classification of Mallet, on a scale of 1 to 5. The mean
      glenoscapular angle (the degree of retroversion of the glenoid) on the affected
      side was -25.7 degrees compared with -5.5 degrees on the unaffected side. Twenty
      six (62 per cent) of the forty-two shoulders had evidence of posterior
      subluxation of the humeral head, with a mean of only 25 per cent (range, 0 to 50
      per cent) of the head being intersected by the scapular line. Progressive
      deformity was found with increasing age (p < 0.001). The natural history of
      untreated brachial plexus birth palsy with residual weakness is progressive
      glenohumeral deformity due to persistent muscle imbalance. The status of the
      glenohumeral joint must be addressed when the choice between tendon transfer and
      humeral derotation osteotomy for reconstruction of the shoulder is considered for
      these patients.

PMID- 9611028
TI  - Total elbow arthroplasty in patients who have juvenile rheumatoid arthritis.
AB  - Patients who have juvenile rheumatoid arthritis often are seen at a very young
      age because of severe stiffness and pain in several joints. While total elbow
      replacement may be indicated in these patients, this procedure is difficult to
      perform because of contracture of the soft tissues and the extremely small bones
      and intramedullary cavities in these patients. As there is little information in
      the literature regarding this procedure, we attempted to learn about the long
      term results by evaluating nineteen patients (twenty-four elbows) with juvenile
      rheumatoid arthritis who had been managed with total elbow arthroplasty. At an
      average of 7.4 years (range, two to fourteen years) after the operation, there
      was an improvement in the average Mayo elbow performance score from 31 points
      (range, 5 to 55 points) preoperatively to 90 points (range, 55 to 100 points).
      Twenty-two (96 per cent) of the twenty-three elbows available at the most recent
      follow-up evaluation caused little or no pain, but the improvement in the range
      of motion was not as reliable. The average arc of flexion improved from only 63
      degrees preoperatively to 90 degrees postoperatively; the average postoperative
      arc of flexion began at 35 degrees, with additional flexion to 125 degrees.
      Examination of the four elbows that had been ankylosed before the procedure
      revealed an average arc of 73 degrees after the operation, and evaluation of the
      twenty ipsilateral wrists that were not limited by disease revealed that
      pronation and supination had been maintained. The average functional score
      improved from 9 points (range, 0 to 25 points) preoperatively to 23 points
      (range, 15 to 25 points) postoperatively (p < 0.001). The function of eighteen
      elbows (78 per cent) did not adversely affect the ability to perform activities
      of daily living. There were thirteen complications, including one perioperative
      death, that affected twelve of the twenty-four elbows. Seven of the nine early
      complications, including a fracture of the olecranon, subluxation of the
      prosthesis, stiffness of the elbow, and problems with wound-healing, led to an
      additional operative procedure but did not adversely affect the long-term outcome
      after appropriate diagnosis and treatment. Late complications (aseptic loosening,
      instability, and worn bushings) led to three poor results. None of the eighteen
      semiconstrained prostheses had radiographic evidence of loosening at the most
      recent follow-up evaluation. Of the twenty-three elbows that had been followed
      for at least two years, twelve (52 per cent) had an excellent result, eight (35
      per cent) had a good result, and three (13 per cent) had a poor result.

PMID- 9611029
TI  - Long-term outcome of lumbar discectomy in children and adolescents sixteen years
      of age or younger.
AB  - We retrospectively reviewed the cases of seventy-two consecutive patients who had
      a lumbar discectomy, between 1950 and 1983, when they were sixteen years of age
      or younger. There were forty boys and thirty-two girls. At the time of the lumbar
      discectomy, twelve patients (17 per cent) also had a spinal arthrodesis. The mean
      duration of follow-up was 27.8 years (range, twelve to forty-five years). Twenty
      patients (28 per cent) had one reoperation or more, with the first reoperation
      performed at a mean of 9.7 years after the initial discectomy. Fourteen patients
      had one reoperation, four had two reoperations, one had three, and one had five.
      Fifty-two patients (72 per cent) did not need a reoperation. At the time of the
      latest follow-up, forty-eight (92 per cent) of the fifty-two patients either had
      no pain or had occasional pain related to strenuous activity and fifty-one (98
      per cent) could participate in daily activities with no or mild limitations.
      Survivorship analysis showed that the overall probability that a patient would
      not need a reoperation was 80 per cent at ten years and 74 per cent at twenty
      years after the initial operation. With the numbers available for study, we could
      not show that age, gender, or an arthrodesis performed at the time of the initial
      operation were risk factors for a reoperation. We could not detect a difference,
      with respect to pain or the level of activity, between the patients who had had
      an arthrodesis at the initial operation and those who had not or between those
      who had a coexisting structural abnormality of the lumbar spine and those who did
      not.

PMID- 9611030
TI  - Reconstruction of the flexor pulley. The effect of the tension and source of the
      graft in an in vitro dog model.
AB  - Flexor pulleys in the hindpaw digits of twenty-eight adult mixed-breed dogs were
      reconstructed in order to investigate the influence, on the reconstruction, of
      the source of the autogenous tissue (intrasynovial compared with extrasynovial
      tendon) and the tension applied during the repair. The ipsilateral peroneus
      longus tendon was used to reconstruct the A2 pulley with an around-the-bone
      technique in twenty-one digits; the graft was sutured at a tension of 0.49, 0.98,
      and 1.96 newtons in seven digits each. The flexor digitorum profundus tendon of
      an adjacent digit was used to reconstruct the A2 pulley, at a tension of 0.98
      newton, in seven additional digits. The contralateral digits were used as
      controls for all twenty-eight treated digits. The digits were tested in a custom
      apparatus designed to measure the frictional force generated between the
      reconstructed pulley and the tendon beneath it. The frictional force did not
      differ significantly (p > 0.5) among the three groups repaired with peroneus
      longus tendon; however, the average value was more than five times that produced
      in the contralateral, control digits. The average frictional forces created by
      the flexor digitorum profundus grafts were similar to those in the contralateral,
      control digits. Reconstruction with the flexor digitorum profundus at a tension
      of 0.98 newton produced significantly less frictional force (p < 0.05) than that
      produced by the peroneus longus graft at the same tension. This in vitro model of
      reconstruction of the A2 pulley demonstrated that tendon from an intrasynovial
      source (the flexor digitorum profundus) produced less frictional resistance to
      gliding of the tendon than did tendon from an extrasynovial source (the peroneus
      longus). This result is consistent with previously published findings that
      intrasynovial tendons may make better grafts than extrasynovial tendons for the
      reconstruction of gliding flexor tendons because of decreased friction and better
      healing qualities. Intrasynovial tendons may also make better grafts for the
      reconstruction of flexor pulleys.

PMID- 9611031
TI  - Charnley total hip arthroplasty in patients less than fifty years old. A twenty
      to twenty-five-year follow-up note.
AB  - We evaluated the results twenty to twenty-five years after ninety-three
      consecutive, nonselected Charnley total hip arthroplasties performed with cement
      by the senior one of us in sixty-nine patients who were less than fifty years old
      at the time of the procedure. Seventy of the seventy-two hips in the living
      patients were followed radiographically for at least twenty years. Twenty-seven
      hips (29 per cent) had a revision or a resection of the prosthesis during the
      follow-up period. The revision or the resection was performed because of aseptic
      loosening in twenty-one hips (23 per cent), infection in four (4 per cent),
      dislocation in one (1 per cent), and fracture of the femur in one. Eighteen
      acetabular components (19 per cent) and five femoral components (5 per cent) were
      revised because of aseptic loosening, and an additional fourteen acetabular
      components (15 per cent) and seven femoral components (8 per cent) demonstrated
      definite or probable radiographic loosening. The present study demonstrates the
      long-term durability of total hip arthroplasty performed with cement in an active
      population of patients. The fixation of the femoral component was found to
      perform better than that of the acetabular component at twenty to twenty-five
      years after the procedure.

PMID- 9611032
TI  - The natural history of debonding of the femoral component from the cement and its
      effect on long-term survival of Charnley total hip replacements.
AB  - Two hundred and ninety-seven consecutive Charnley total hip replacements that had
      been followed for at least twenty years or until revision or death were analyzed
      to determine the effect of early debonding of the smooth-surfaced femoral
      component on its subsequent survival. Radiographically evident debonding was not
      found to have a significant effect, with the numbers available, on the long-term
      survival of the femoral component when the maximum thickness of the radiolucent
      line between the superolateral border of the prosthesis and the cement had been
      less than 2.0 millimeters during the first one to five years after the operation.
      The radiographic finding of debonding also was not found to be associated with
      pain in the hip. These data show that most components with early debonding
      functioned well during a long period of follow-up and suggest that debonding of a
      smooth femoral component of a Charnley total hip replacement should not be
      considered to be analogous to loosening. In contrast, when the maximum thickness
      of the radiolucent line between the superolateral border of the prosthesis and
      the cement was 2.0 millimeters or more, an early appearance of debonding was
      associated with a significantly poorer (p < 0.0001) probability of survival of
      the Charnley femoral component without revision because of aseptic loosening.
      Thus, pronounced early subsidence of the component within the cement mantle had a
      strong negative impact on the long-term performance of the implant. The results
      of the present study should not be extrapolated to prostheses with substantially
      different design characteristics, as it appears that different types of femoral
      components behave differently when debonding occurs.

PMID- 9611033
TI  - Recurrent meningitis secondary to infection after spinal arthrodesis with
      instrumentation. A case report.

PMID- 9611034
TI  - Extraskeletal osteosarcoma of the hand. A case report.

PMID- 9611035
TI  - Peridiscal metastatic carcinoma associated with lumbar disc herniation. A case
      report.

PMID- 9611036
TI  - Debridement of partial-thickness tears of the rotator cuff without acromioplasty.
      Long-term follow-up and review of the literature.

PMID- 9611037
TI  - Current concepts review. Treatment of metastatic adenocarcinoma of the pelvis and
      the extremities.

PMID- 9611038
TI  - Pyogenic vertebral osteomyelitis.

PMID- 9611039
TI  - Wear of polyethylene acetabular components in total hip arthroplasty. An analysis
      of one hundred and twenty-eight components retrieved at autopsy or revision
      operations.

PMID- 9611040
TI  - The natural history of untreated asymptomatic hips in patients who have non
      traumatic osteonecrosis.

PMID- 9611041
TI  - Measurement of polyethylene wear in acetabular components inserted with and
      without cement. A randomized trial.

PMID- 9611042
TI  - A self-administered questionnaire for assessment of symptoms and function of the
      shoulder.

PMID- 9611043
TI  - Side-to-side confrontational strength-testing for weakness of the intrinsic
      muscles of the hand.

PMID- 9611044
TI  - Long-term outcome after open reduction through an anteromedial approach for
      congenital dislocation of the hip.

PMID- 9611045
TI  - Spinal epidural compression complicating cancer of the cervix: review of seven
      cases.
AB  - Records of women with newly diagnosed cancer of the cervix during a 16-year
      period were reviewed retrospectively for the development of spinal epidural
      compression by metastatic tumor (SECMT). Of the 361 cases studied, seven patients
      (2%) experienced SECMT. Epidural compression often involved the lumbar segment,
      tended to occur in the nonelderly population, and was relatively protracted in
      onset following the diagnosis of cervical cancer in cases of metachronous
      presentations. Although the prognosis was generally poor, the application of
      therapy may have promoted a better quality of remaining life by relieving pain or
      restoring the ability to walk.

PMID- 9611046
TI  - Pleurodesis with recombinant tumour necrosis factor in gynaecological neoplasms.
AB  - Recombinant Tumour Necrosis Factor (rHuTNF) was locally applied to 18 patients
      with gynaecological tumours and recurrent malignant pleural effusions. Twenty
      nine administrations with doses between 0.10 mg and 0.50 mg were carried out.
      Side-effects were flu-like symptoms (41%), fever/chill (34%), fatigue/malaise
      (28%), nausea/vomiting (10%), chest pain (14%). A dose-toxicity or dose-response
      relationship could not be established. Eighty-eight percent of the patients
      treated with rHuTNF did not suffer from any recurrent effusion within 4 weeks
      after treatment. Regarding the total survival time after therapy with rHuTNF 78%
      of all patients did not require any further pleural aspiration. Instillation of
      rHuTNF appears to be an effective method which can be used for pleurodesis with
      relatively few side-effects. It is a treatment which can also be applied to
      patients who are in a poor general state of health. It is especially
      recommendable since it can be successfully applied even after other pleurodesis
      devices have failed.

PMID- 9611047
TI  - Culture of ascitic ovarian cancer cells as a clinically-relevant ex vivo model
      for the assessment of biological therapies.
AB  - There are few in vitro models of human ovarian cancer suitable for the assessment
      of biological therapies. We have established short-term cultures of ovarian
      carcinoma cells from ascites, maintained in suspension in ascitic fluid to help
      preserve the original tumor cell microenvironment. We assessed the effects of a
      potential biological therapeutic agent, interferon-alpha (IFN alpha), on ovarian
      cell phenotype. In total, eight cultures were established from seven patients.
      Quantitative changes in cell surface phenotype were determined by flow cytometry
      for HLA-ABC, HLA-DR, TAG72, CA125, HMFG1 and HMFG2 antigens. The amount of CA125
      antigen shed into the culture media was also assessed. Variations in cell surface
      phenotype between specimens probably reflected the specific cytokine milieu of
      the ascites as well as idiotypic differences between tumors. Nevertheless, there
      were consistent phenotypic responses to IFN alpha, with up-regulation of MHC
      Class I but down-regulation of the HMFG1 and HMFG2 antigens from the cell
      surface. The results suggest that this approach may be useful in patient
      selection and for optimizing biological therapies, as it enables patients'
      individual tumor responses to exogenous cytokine to be studied against the
      background of the endogenous cytokine milieu.

PMID- 9611048
TI  - The value of colposcopy in screening cervical carcinoma.
AB  - The value of colposcopy and cytology in screening CIN was analyzed in a
      retrospective study of 1,504 patients treated at the Department of Gynecologic
      Oncology, National Institute of Oncology, Budapest from 1980 to 1991. The
      majority (1,451) of the patients were admitted for histological confirmation of
      atypical colposcopic and/or cytologic findings, and 53 women were treated for
      cervical repair. All women underwent either cervical excision or conization.
      Cytologic and colposcopic findings were compared with the histological results.
      Sensitivity and specificity rates of cytology were 47% and 77%, respectively. The
      corresponding figures for colposcopy were 87% and 15% and for cytology and
      colposcopy together, 96% and 14%. The low sensitivity of cytology suggests that
      as many as 50% of CIN lesions may be overlooked if cytology alone is used for
      screening, i.e. in 50% of CIN associated with abnormal colposcopy the cytology
      was negative. We found 194 asymptomatic patients with carcinoma in situ, 40 with
      microinvasive and 8 with frank invasive carcinoma. This finding emphasizes the
      importance of cervical cancer screening. Our data suggest that, with colposcopy
      as a screening tool, the rate of false-negative cytology can be significantly
      reduced. Clinical implications of the "cytology-negative abnormal colposcopy and
      cytology-negative CIN" have yet to be determined. The major drawback of primary
      colposcopy is its low specificity with the consequence of high false-positive
      rate and over-treatment in a substantial number of cases. To overcome the problem
      of low specificity, further studies are required to identify those atypical
      colposcopic changes that most likely represent CIN--and high-grade CIN in
      particular.

PMID- 9611049
TI  - Biologic prognostic factors in ovarian cancer: a review.
AB  - The need of foreseeing the prognosis of ovarian cancer beyond the limits of
      classical methods based on clinical and histopathological staging has recently
      caused great interest in a large number of biologic prognostic markers. Studies
      concern proliferation associated proteins, suppressor genes, abnormal expressions
      of growth factors, cytokins, and many more. Here some of the most recent and
      promising factors being studied are described together with their significance
      for future clinical application.

PMID- 9611050
TI  - Aztreonam plus piperacillin--empiric treatment of neutropenic fever in gynecology
      oncology patients receiving cisplatin-based chemotherapy.
AB  - Antibiotic therapy must be instituted promptly and on an empiric basis in
      neutropenic patients. We evaluated the efficacy of a combined antibiotic regimen
      of monobactam (aztreonam) and antipseudomonal penicillin (piperacillin) in
      treating neutropenic fever episodes in gynecologic-oncology patients receiving
      cisplatin-based chemotherapy. A retrospective analysis of response to this
      regimen was performed. The rationale of this combination is the lack of
      nephrotoxicity and ototoxicity in patients who are or were previously treated
      with other nephrotoxic/ototoxic agents like cisplatin. A total of 19 courses of
      this regimen was administered to 13 patients with neutropenic fever following a
      complete fever work-up. Aztreonam (1-2gr q8h) plus piperacillin (4gr q8h) were
      administered intravenously for 6-8 days. Blood cultures were positive in four
      febrile episodes, and urine cultures were positive in seven. Gram negative
      organisms accounted for all positive cultures. The cultured organism showed in
      vitro sensitivity to at least one of the drugs in all positive isolates. Clinical
      response with defervescence was noted during therapy in 18/19 courses (94.7%).
      Although the two drugs share a common bactericidal mechanism they were found to
      be highly active in this subgroup of patients. A double blind prospective
      evaluation of this empiric combination is warranted.

PMID- 9611051
TI  - Ovarian germ cell tumors.
AB  - Ovarian germ cell tumors (OGCT) are a special type of ovarian cancers due to
      their histology, age of presentation, prognosis and treatment. MATERIAL AND
      METHODS: Eighteen cases of OGCT out of 313 total ovarian cancer diagnosed in
      Hospital Materno-Infantil Vall d'Hebredn between 1975 and 1994 are present.
      RESULTS: Mean age of the patients was 36 years. The most frequent symptom at
      diagnosis was abdominal bloating (44.5%). Echography was the most used diagnostic
      method (67%). Surgery was conservative in 44% of the cases, radical in 50% of the
      cases and palliative in one case. The histological types were 6 dysgerminomas and
      6 malignant teratomas (33.3%), 3 malignant dermoid cysts (16.7%), 2 yolk sac
      tumors (11%) and 1 embryonal carcinoma. According to FIGO 1987 staging
      classification 14 patients were in stage I disease and 4 in stage III disease.
      Polychemotherapy was performed on 6 patients and postsurgical radiotherapy was
      performed on 2 patients. Five patients recurred in an average time of 25 months.
      The five-year survival rate, according to the Kaplan-Meier method, was 80% in
      stage I and 0% in stage III. Five-year survival rate of patients only surgically
      treated was 65% and in patients who underwent postsurgical co-adjuvant treatment
      it was 100%. CONCLUSION: Conservative surgery followed by a BEP regimen may be
      performed nowadays with efficacy and acceptable toxicity while conserving the
      fertility of these patients.

PMID- 9611052
TI  - Serologic profile of some sexually transmitted diseases in women with squamous
      intraepithelial lesions.
AB  - The purpose of this study consisted of the evaluation of some sexually
      transmitted diseases in patients with cervical pathology, namely squamous
      intraepithelial lesions. METHODS: a prospective study was performed. Patients
      with an abnormal cervical smear were submitted to colposcopy, directed biopsy and
      an immunologic assay for Chlamydia, Herpes Simplex Virus (HSV) types 1 and 2,
      Cytomegalovirus, Treponema pallidum, Hepatitis B and Human Immunodeficiency Virus
      I and II. The same parameters were evaluated in women with normal cervical
      cytology in a matched control group. A comparative study was performed evaluating
      some epidemiological parameters and the referred immunologic assays. RESULTS: 118
      patients were separated into four groups. Statistically significant differences
      were observed in the personal history of fungi infections, as well as Chlamydia
      and HSV 2 IgM. CONCLUSION: immunologic assays may prove useful in identifying
      sexually-transmitted diseases, especially Chlamydia and HSV 2 infections, in
      Human Papillomavirus infected women.

PMID- 9611053
TI  - Primary tubal carcinoma: a retrospective analysis of four cases with a literature
      review.
AB  - With an incidence of 0.1% to 1.0% of all genital malignancies, primary tubal
      carcinoma is a rare malignant disease of the female genital tract. The prognosis
      is generally regarded as very poor. It is comparable with that of ovarian
      carcinoma. From 1980-1995, four patients were treated for primary tubal carcinoma
      at the Department of Gynecology and Obstetrics at the University of Homburg/Saar.
      FIGO stages IIa-IV were manifested as the primary stage. Surgery was performed as
      primary treatment in all patients. Both chemotherapy and percutaneous radiation
      were used as adjuvant postoperative therapy. The recurrence-free interval was 18
      30 months. One patient died 21 months after primary diagnosis. The other free
      patients are in a period of follow-up observation of 16-96 months in an NC or CR
      status.

PMID- 9611054
TI  - Expression of p53 protein in borderline epithelial ovarian tumors: a
      clinicopathologic study of 39 cases.
AB  - OBJECTIVE: To evaluate the expression of p53 protein in borderline ovarian tumors
      and its correlations with the clinicopathological parameters. STUDY DESIGN: p53
      protein was detected by immunoperoxidase in 79 ovarian tumors (39 borderline, 20
      malignant, 20 benign). p53 expression was compared to histological type, FIGO
      stage, age, presence of ascites, recurrence and patient survival. RESULTS: The
      median value of quantitative p53 immunopositivity was: 0.80+/-0.42 in ovarian
      cancers, 0+/-0.24 in borderline tumors and 0+/-0.16 in benign tumors (p=0.001).
      In borderline tumors, no correlation existed between p53 expression and the
      histological or clinical parameters. In malignant tumors, no correlation existed
      between the expression of p53 and patient survival. CONCLUSION: We found no
      correlation between p53 immunopositivity and clinicopathological parameters in
      carcinomas and borderline tumors of the ovary. p53 immunopositivity may help in
      distinguishing borderline tumors from ovarian cancers.

PMID- 9611055
TI  - Thyroid function in postmenopausal women with breast cancer on tamoxifen.
AB  - In 42 postmenopausal women with breast cancer, aged 48-85 years (mean age 62.4
      years) serum thyroid hormone concentrations were measured before and after 6
      months of tamoxifen therapy (20 mg daily). In particular triiodothyronine (T3),
      thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), thyroxine
      binding globulin (TBG) and thyroid-stimulating hormone (TSH) concentrations
      before and 30 minutes after thyrotrophin-releasing hormone (TRH) administration
      (200 microg i.v.) were measured before and 6 months after tamoxifen therapy. T3
      and T4 concentrations increased significantly (p<0.001 and p<0.05, respectively)
      whereas FT3 and FT4 remained unchanged (p>0.05), TBG increased significantly
      (p<0.001) and basal TSH concentrations as well as TSH response to TRH injection
      increased significantly (p<0.05) after tamoxifen therapy. It is concluded that
      tamoxifen administration changes thyroid hormone concentrations. However free
      thyroid hormone levels remain unchanged and the patients remain euthyroid after
      long-term tamoxifen therapy.

PMID- 9611056
TI  - Long-term chemotherapy of ovarian cancer: two case reports.
AB  - The treatment period of patients with advanced ovarian cancer is generally
      limited to about six months and maintenance chemotherapy is seldom used. The
      present report describes two women given chemotherapy continuously for several
      years with apparently good efficacy and acceptable toxicity.

PMID- 9611057
TI  - Angiogenesis as a prognostic factor in cervical carcinoma.
AB  - Angiogenesis and other prognostic factors have been studied among 32 recurrences
      and 28 deaths of 420 patients with cervical carcinoma operated in the 1st
      Department of Obstetrics & Gynecology of Catania University. Prognostic factors
      were studied in comparison with a group of patients still alive and NED was
      followed for more than 60 months independently of stage and node involvement.
      Angiogenesis, nuclear grading 3, and lymphovascular invasion were factors common
      to all patients with negative prognosis. It seems that in the presence of these
      negative prognostic factors, we should adopt a more aggressive attitude in both
      our surgical strategies and adjuvant therapies, particularly preferring
      chemotherapy where angiogenesis is more significant.

PMID- 9611058
TI  - 99mTc Tetrofosmin imaging in breast tumours.
AB  - Eighty-five women, 18 to 80 years of age, with palpable breast lumps were studied
      1-4 days before surgery in order to evaluate 99mTc Tetrofosmin imaging for the
      detection of malignant breast tumours. Intravenous injection of 99mTc Tetrofosmin
      was followed by 3 min planar images at 5-60 min postinjection. In the latter 57
      patients, planar imaging was preceded by a dynamic study of 20x5 sec images. The
      myocardium was always included in the field of the left breast. Count rates in
      suspicious areas were compared with normal tissue areas in the same and the
      opposite breast and with myocardial counts. Data analysis showed that 77 of the
      85 scan results were in agreement with the histological findings; six scans were
      false negative and two false positive for malignancy. The sensitivity of the
      method was 90.32% and the specificity 91.30%, with a positive predictive value of
      96.55%. We conclude that breast scanning with 99mTc Tetrofosmin may play an
      important role in the detection of breast malignancies.

PMID- 9611059
TI  - Hepatoid carcinoma of the ovary--a case report.

PMID- 9611060
TI  - Low-malignant potential epithelial tumors of the ovary: a clinicopathological
      study.
AB  - Low-malignant potential (LMP) epithelial tumors of the ovary are a group which
      occupy an intermediate position between the benign and those of the frankly
      malignant ovarian neoplasms. The actual incidence, present age and treatment are
      still being discussed. During the period 1991-1996, from the 650 ovarian tumors
      which were diagnosed and treated in our institution, 401 were epithelial tumors.
      The LMP serous epithelial tumors consisted of 4.36% of all serous tumors while
      LMP mucinous tumors were 9.70% of all mucinous tumors. The LMP serous tumors had
      an 8 cm diameter on average, 83% were unilocular and 76.5% unilateral. The LMP
      mucinous tumors had a 17 cm diameter on average, 95% were multilocular and 95%
      unilateral. The mean age at diagnosis was 39 years for LMP serous tumors and 48
      years for LMP mucinous tumors.

PMID- 9611061
TI  - Venous port systems in the field of gynaecological oncology.
AB  - In the field of gynaecological oncology, which is characterised by the frequent
      application of cytotoxic drugs strongly necrotising to tissue, fully implantable
      venous port systems are of particular relevance. Frequent and serious
      complications such as infection, thrombosis, obstruction, leakage, or
      paravasation detract considerably, however, from the advantages otherwise
      deriving from a safe and reliable means of accessing a patient's venous system.
      Most complications are caused by the inexpert handling of these fully implantable
      catheters and should, therefore, be avoidable. In many cases, it will be possible
      after efficient diagnosis to solve the complication and keep the port
      functioning. On the basis of 8 actual cases typical and frequent complications
      observed in connection with port systems are described, together with preventive
      measures, diagnosis and therapy.

PMID- 9611062
TI  - Cervical intraepithelial neoplasia and HPV infection.
AB  - Human papillomavirus (HPV) infection has been recognized as the major cause of
      cervical cancer [1]. The transformation zone of the cervix is the most frequent
      target of the high risk HPV types. In our study infection with HPV16 and 18 was
      investigated in the cervical scrapes of 28 subjects with cervical intraepithelial
      neoplasia. The DNAs isolated from the samples were amplified by dot-blot
      hybridization with fragmented digoxygenin labelled probes. Eighteen of 28
      patients (64.3%) were found positive for HPV-16, eleven (39.3%) were found
      positive for HPV-18 and six patients (21%) were infected with both HPV types.
      This method is practical and sensitive for determining patients with a higher
      risk of developing HPV-related cancer.

PMID- 9611063
TI  - Borderline ovarian tumours: retrospective analysis of twenty-one cases.
AB  - Twenty-one borderline ovarian tumour cases, diagnosed and treated in our oncology
      section between 1986 and 1996, were retrospectively analysed. Thirty-three
      percent of the cases had serous tumours and the rest (66.6%) were mucinous, 57.1%
      of the mucinous tumours were the intestinal type and the remaining 42.9% were the
      endocervical type. When all the cases were analysed, the average age was 45.4+/
      18.6 years, the average follow-up period was 5.5+/-2.6 years. The preoperative
      average CA125 level was 55.1+/-51.9 U/mL, and for CA19.9 it was 48.2+/-47.8 U/mL.
      Of the patients 85.7% were stage I and 14.3% state III. There were not any
      significant differences between the serous, intestinal-type mucinous and
      endometroid-type mucinous tumours regarding tumour volumes (p>0.05). When serous
      and mucinous tumours were compared according to the tumour markers, CA125 levels
      were significantly higher in the serous tumours (p=0.04) and CA19.9 levels were
      significantly higher in the mucinous tumours (p=0.02). All of the patients are
      under our follow-up and are in remission, except one, who died in the third year
      of the treatment because of chronic renal failure unrelated to the ovarian
      pathology.

PMID- 9611065
TI  - Small cell carcinoma of the cervix: analysis of clinical and pathological
      findings.
AB  - PURPOSE OF INVESTIGATION: An attempt to better identify small cell carcinoma of
      the cervix and evaluate its prognosis. METHODS: From January of 1970 to March of
      1995, a total of seven patients diagnosed with small cell carcinoma of the cervix
      by pathologic revision were retrospectively reviewed. Clinical information
      including age, clinical stage, lymph-vascular space invasion, lymph node
      metastases, prognoses were analyzed. RESULTS: All specimens stained positive for
      neuron-specific enolase (NSE) and four were positive for chromogranin (CGR). The
      majority of patients (71%) died of disease within 18 months. Only one patient had
      an abnormal Pap smear before definite diagnosis, and only one patient was well
      and alive after a combination of surgery and multi-agent chemotherapy (p<0.05).
      CONCLUSION: Pap smears may not be an appropriate screening method for detecting
      small cell carcinoma of the cervix. Immunohistological staining may be helpful in
      diagnosis of small cell carcinoma of the cervix. Because of a very poor
      prognosis, more effective therapeutic protocol should be further defined in the
      management of cervical small cell carcinoma.

PMID- 9611064
TI  - Primary malignant melanoma of the vagina: case report.
AB  - Primary vaginal melanoma is a very rare gynecological malignant tumor (less than
      150 reported cases to-date). Prognosis is poor in spite of treatment. Due to the
      fact that only small groups of patients have been compared, conservative
      treatment has usually been recommended. In recent times, radical pelvic surgery
      has appeared to improve the chances of survival. We present an unusual case of
      primitive melanoma of the upper-third of the vagina with urethral and urinary
      bladder infiltration in a 47-year-old woman. Treatment consisted of preliminary
      pelvic bilateral lymphadenectomy, anterior exenteration, and urinary bladder
      reconstruction according to the Bricker technique. Four months after surgical
      treatment, liver metastases were found. Chemotherapy was initiated consisting of
      8 cycles every 21 days of fotemustine 100 mg/m2 (day 1) and dacarbazine (DTIC)
      250 mg/m2 (days 2-5). Interferon alpha-2-b, 3 MU thrice weekly, for the whole
      period of chemotherapy, was also administered. The patient is in partial
      remission one year after surgical treatment.

PMID- 9611066
TI  - Toward understanding the pathogenesis of craniosynostosis through clinical and
      molecular correlates.

PMID- 9611067
TI  - Rapid determination of trisomy 18 parental origin using fluorescent PCR and small
      tandem repeat markers: case reports.
AB  - Trisomy 18 is the second most common genetic defect after trisomy 21, almost 90%
      of which are due to additional chromosome from the mother. The parental origin of
      the additional chromosome can, if required, be determined by two methods:
      karyotyping, which takes several weeks; or, more recently, by polymerase chain
      reaction (PCR) which is often problematic. Fluorescent PCR of small tandem
      repeats (STRs) can determine the parental origin in the majority of cases within
      5 h. Although the incidence of paternal origin is known for both trisomy 21 and
      trisomy 18, this technique can rapidly determine the parental origin in cases
      where there is insufficient samples to perform conventional tests. Determining
      parental origin by these methods may also have clinical significance in the
      diagnosis of chromosomal translocations or in the diagnosis of genetic disease
      using linkage analysis.

PMID- 9611068
TI  - Brother/sister siblings affected with Hunter disease: evidence for skewed X
      chromosome inactivation.
AB  - Hunter disease is an X-linked recessive disorder caused by a deficiency of
      iduronate-2-sulfatase activity. We describe a pair of brother/sister siblings
      with a typical feature of Hunter disease (mucopolysaccharidosis type II). They
      had normal karyotypes but a marked deficiency of iduronate-2-sulfatase activity
      in both lymphocytes and fibroblasts. The molecular analysis of the iduronate-2
      sulfatase gene revealed the R468L(G1403-->T) substitution in their genes.
      Although the sister's genomic DNA was heterozygous for the mutant allele, the
      sister's cDNA was found to be homogeneous for this mutation. The mother was found
      to be a heterozygote. The analysis of X chromosome inactivation by comparison of
      the methylation patterns of the androgen-receptor (AR) gene which was isolated
      from the sister's fibroblasts and leucocytes revealed a skewed X chromosome
      inactivation of the paternal allele. These findings indicate that a skewed X
      chromosome inactivation of the paternal gene and a point mutation in the maternal
      gene were responsible for the lack of iduronate-2-sulfatase activity in the
      sister.

PMID- 9611069
TI  - Skewed X inactivation in manifesting carriers of Duchenne muscular dystrophy.
AB  - We studied X inactivation patterns in manifesting carriers of familial and
      sporadic Duchenne muscular dystrophy (DMD) or unaffected carriers of DMD by
      analysis of the methylation of HpaII sites in the first exon of the human
      androgen-receptor gene (HUMARA) from peripheral blood samples. Three of the four
      manifesting carriers, four of the five asymptomatic carriers, and 31 of the 32
      female controls were heterozygous for the CAG repeat of HUMARA. All manifesting
      carriers showed skewed X inactivation, while all unaffected carriers showed
      almost symmetrical inactivation. One family studied over three generations is
      noteworthy because it includes two mother/daughter pairs, one an affected pair
      with skewed X inactivation, and the other a phenotypically normal carrier pair
      with random X inactivation. On the other hand, the extent of X inactivation for
      each X chromosome in 31 female controls was widely distributed. These data
      suggest that in carriers of DMD, both affected and unaffected, it is valuable to
      analyze the pattern of skewed X inactivation because it provides important
      prognostic information. Carriers of DMD with skewed X inactivation might show
      slowly progressive myopathy with advancing age.

PMID- 9611070
TI  - Clinical, morphological and biochemical features in the familial articular
      hypermobility syndrome (FAHS): a family study.
AB  - A female with clinical features of familial articular hypermobility syndrome
      (FAHS) and her family were studied. The subject showed generalized hypermobility,
      except for a painful shoulder which presented functional limitation with a
      diagnosis of painful shoulder syndrome. Biochemical studies demonstrated that
      collagen and glycosaminoglycans (GAGs) contents from skin biopsies of the subject
      and her family were almost normal. Nevertheless, the densitometric analysis of
      electrophoretic patterns showed differences in the relative proportions of their
      collagenous components. They were characterized by changes in type I and III
      collagens and the presence of type V collagen, in the subject, her father and
      brother. Also, they presented changes in the types of GAGs, when compared with
      those of normal skin. Morphological studies revealed a general disorganization of
      dermal components, a loose collagen network characterized by thick bundles. Also,
      besides cellular elements, the presence of an abundant darkly staining material
      was observed. Biochemical and morphological findings permit us to suggest a
      connective tissue defect, initially described in the FAHS, otherwise known as
      Ehlers Danlos syndrome (EDS) type XI.

PMID- 9611071
TI  - Maternal cell contamination of buccal smear samples in nursing neonates.
AB  - Buccal smear analysis is a non-invasive method which is being popularized by new
      fluorescence in situ hybridization (FISH) techniques. It is frequently used for
      gender identification and detection of sex chromosome aneuploidy in neonates. We
      attempted to determine whether or not buccal smears of nursing infants can be
      contaminated by maternal cells from breast feeding. FISH involving centromere
      specific directly labeled, multicolor probes for chromosomes X, Y and 18 were
      used for analysis of buccal smear samples. Buccal smear samples from 22 breast
      fed and 20 formula fed male neonates were analyzed in a blinded fashion. Twenty
      seven percent of samples from breast fed infants had some (0.5-2.5%) XX signal
      pattern while the samples from formula fed infants had no XX signal pattern
      (difference statistically significant, p < 0.02, at 95% confidence interval). Our
      results indicate that breast feeding can cause maternal cell contamination of
      buccal smear samples that can lead to misinterpretation of results involving FISH
      analysis or other DNA based diagnostic studies. We have also modified the FISH
      technique to suit the neonates.

PMID- 9611073
TI  - Vascular anastomoses leading to amelia and cutis aplasia in a dizygotic twin
      pregnancy.
AB  - Dichorionic placentation is observed in both monozygotic (MZ) and dizygotic (DZ)
      twinning, while monochorionic placentation is unique to MZ twinning. Examinations
      of monochorionic twin placentas frequently reveal the presence of vascular
      anastomoses between the two fetal circulations; such anastomoses rarely occur in
      dichorionic placentas. Consequently, abnormalities resulting from placental
      vascular communications are almost exclusively observed in MZ twin pairs with
      monochorionic placentas. We report opposite-sex DZ twins in which vascular
      anastomoses occurred within a fused dichorionic placenta and were associated with
      vascular disruptions in one twin. The liveborn male twin had amelia, cutis
      aplasia, and XX/XY blood chimerism; the female twin died in utero.

PMID- 9611072
TI  - Molecular genetic analysis of the gene encoding the trifunctional enzyme MTHFD
      (methylenetetrahydrofolate-dehydrogenase, methenyltetrahydrofolate
      cyclohydrolase, formyltetrahydrofolate synthetase) in patients with neural tube
      defects.
AB  - It is now well recognized that periconceptional folic acid or folic acid
      containing multivitamin supplementation reduces the risk of neural tube defects
      (NTDs). Recently we were able to show that homozygosity for a thermolabile
      variant of the enzyme methylenetetrahydrofolate reductase is associated with an
      increased risk for spina bifida in patients recruited from the Dutch population.
      However, this genetic risk factor could not account for all folic acid
      preventable NTDs. In an attempt to identify additional folate related enzymes
      that contribute to NTD etiology we now studied the methylenetetrahydrofolate
      dehydrogenase gene on chromosome 14q24 which encodes a single protein with three
      catalytic properties important in the folate metabolism. The cDNA sequence of 38
      familial and 79 sporadic patients was screened for the presence of mutations by
      single strand conformation polymorphism (SSCP) analysis followed by sequencing.
      Two amino acid substitutions were identified. The first one (R293H) was detected
      in a patient with familial spina bifida and not in 300 control individuals. The
      mutation was inherited from the unaffected maternal grandmother and was also
      present in two younger brothers of the index patient, one of them displaying
      spina bifida occulta and the other being unaffected. The second change turned out
      to be an amino acid polymorphism (R653Q) that was present in both patients and
      controls with similar frequencies. Our results so far provide no evidence for a
      major role of the methylenetetrahydrofolate-dehydrogenase (MTHFD) gene in NTD
      etiology. However, the identification of a mutation in one family suggests that
      this gene can act as a risk factor for human NTD.

PMID- 9611074
TI  - DGGE screening of mutations in mismatch repair genes (hMSH2 and hMLH1) in 34
      Swedish families with colorectal cancer.
AB  - Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominantly
      inherited syndrome which confers an increased risk for colorectal cancer and
      endometrial cancer as well as other tumors. It is caused by germline DNA mismatch
      repair (MMR) gene mutations in five MMR genes, hMSH2, hMLH1, hPMS1, hPMS2 and
      hMSH6. Finding mutations in these high risk families means that you can offer
      presymptomatic carrier diagnosis and thereby identify individuals with a very
      high risk for cancer. These persons benefit from counseling and should be offered
      surveillance. We have used DGGE to screen members from 34 families for mutations
      in hMLH1 and hMSH2. Six mutations in five families were found, five of these
      mutations are new. Besides, three new polymorphisms were identified. The
      mutations were found in two of seven Amsterdam criteria HNPCC families and in
      three of four families with at least one case of early onset of CRC (before 35),
      suggesting there are appropriate families to be chosen for mutation screening in
      MMR genes.

PMID- 9611075
TI  - Inherited microdeletion in Xp21.3-22.1 involved in non-specific mental
      retardation.
AB  - X-linked mental retardation (XLMR) is a genetically and clinically heterogeneous
      common disorder. A cumulative frequency of about 1/600 male births was estimated
      by different authors, including the fragile X syndrome, which affects 1/4000
      males. Given this very high cumulative frequency, identification of genes and
      molecular mechanisms involved in other XLMRs, represents a challenging task of
      considerable medical importance. In this report we describe clinical and
      molecular investigations in the family of a mentally retarded boy for whom a
      microdeletion in Xp21.3-22.1 was detected within the frame of a previously
      reported systematic search for deletion using STS-PCR screening. Thorough
      clinical investigation of the sibling showed that two affected brothers exhibit a
      moderate non-specific mental retardation without any additional neurological
      impairment, statural growth deficiency or characteristic dysmorphy. Molecular
      analysis revealed that the microdeletion observed in this family is an inherited
      defect which cosegregates with mental retardation as an X-linked recessive
      condition, since both non-deleted boys and transmitting mother are normal. These
      results and the inherited microdeletion detected within the same region
      associated with non-specific MR, reported by Raeymaekers et al., suggest that
      Xp21.3 MR locus is prone to deletions. Therefore, search for microdeletions in
      the eight families assigned by linkage analysis to this region might allow a
      better definition of the critical region and an identification of the gene
      involved in this X-linked mental retardation.

PMID- 9611076
TI  - A case of insertional translocation involving chromosomes 2 and 4.
AB  - We report on a 6-year-old Caucasian boy with direct insertion of genetic material
      from the short arm of chromosome 4 to the short arm of chromosome 2. He was
      referred for evaluation because of global developmental delay and seizure
      disorder. A karyotype performed at 4 1/2 months of age, by a laboratory
      elsewhere, reportedly showed a deletion of chromosome 4(p12). When we saw him, he
      had macrocephaly, hypotonia, psychomotor retardation, multiple minor congenital
      anomalies, and EEG abnormalities. Repeat chromosomes performed by our laboratory
      revealed that his karyotype was 46,XY,dir ins(2;4)(p24;p15.3p13). Fluorescence in
      situ hybridization (FISH) analysis, using chromosomes 2 and 4 painting probes
      confirmed that material from 4p has been translocated to 2p. Also, FISH analysis
      using the Wolf-Hirschhorn critical region probe revealed that both loci are
      intact. Parental chromosomes were normal. This complex rearrangement, though it
      appears balanced, probably might have resulted in either a structural loss of
      genetic material or functional loss of a gene action. Thus, his phenotype could
      be explained by this de novo insertion of chromosome 4 material into chromosome
      2. There is no reported case of this specific chromosome rearrangement.

PMID- 9611077
TI  - No relation between apolipoprotein E alleles and obstructive sleep apnea.
AB  - Apolipoprotein E (ApoE) is a genetic risk factor influencing the development of
      cardiovascular diseases and Alzheimer's disease. Patients with obstructive sleep
      apnea (OSA) suffer an excess mortality and morbidity from cardiovascular
      diseases. The frequencies of ApoE alleles were determined in 291 patients with
      OSA and 728 controls. The distribution of ApoE alleles and genotypes showed no
      difference between OSA and controls.

PMID- 9611078
TI  - High frequency of IgE receptor Fc epsilonRIbeta variant (Leu181/Leu183) in
      Kuwaiti Arabs and its association with asthma.
AB  - The presence of IgE receptor Fc epsilonRIbeta polymorphism (181/183) was
      investigated in Kuwaiti asthmatic patients and controls using an allele
      refractory mutation screening (ARMS) test. The variant sequence (Leu181/Leu183)
      was detected in 72% (320/442) chromosomes analysed. Homozygous LL genotype was
      detected in 48% (46/96) asthmatic subjects compared to 31% (39/125) in non
      asthmatics. In 11/52 families mothers of the asthmatic children were themselves
      asthmatic and 3/11 asthmatic mothers had homozygous LL genotype. 80% of the
      homozygous LL asthmatics showed a positive skin prick test (SPT) compared with
      28% of non-asthmatics with the same genotype. In heterozygous NL asthmatics a
      positive SPT was found in 60% cases compared to 17% in non asthmatics with the
      same genotype. The incidence of hay fever (HF) and eczema (E) was also found to
      be higher in homozygous LL asthmatics compared with the non-asthmatics with the
      same genotype. This study reports a high prevalence of IgE receptor Fc
      epsilonRIbeta variants in Kuwaiti Arabs compared with British, Australian and
      Austrian populations studied before. The association of Leu181/Leu183 variant
      with asthma in Kuwaitis underlines its significance as a risk factor in
      manifesting the clinical phenotype in this population.

PMID- 9611079
TI  - Chromosomal instability in Marinesco-Sjogren syndrome associated with acute
      myeloblastic leukemia.

PMID- 9611080
TI  - The Nordic Comparative Study on Sectorized Psychiatry: contact rates and use of
      services for patients with a functional psychosis.
AB  - As part of a Nordic comparative study on contact rates of new patients and use of
      services in seven catchment areas, contact rates and use of services for patients
      with a functional psychosis during a 1-year follow-up period were investigated.
      The highest contact rates were found in two large city catchment areas in
      Stockholm and Copenhagen. Compared to other patients in the cohorts, patients
      with a functional psychosis were more often found to be unemployed and living
      alone. They also showed more extensive service use in terms of both voluntary and
      compulsory admissions, and in the use of day-care facilities. In addition, they
      were more often multiple users of in-patient care (> or =3 admissions during the
      follow-up period). Large differences in service use among patients with a
      functional psychosis were discovered between the catchment areas, with the most
      extensive use of voluntary in-patient care and day-care facilities in
      Frederiksberg. Patients most frequently had compulsory admissions in Bodo and
      least frequently had them in Frederiksberg. Out-patient services were most
      frequently used in Stockholm. Correlations between levels of resources and use of
      services for patients with a functional psychosis were in general low, except for
      the rates of short-term beds, which showed a strong and significant correlation
      with the number of days in voluntary in-patient care (r=0.89).

PMID- 9611081
TI  - Sex difference in age at onset of schizophrenia: discrepant findings from India.
AB  - Consecutive male (n=100) and female (n=100) DSM-IV schizophrenics newly
      registered for treatment in a large psychiatric hospital were examined with
      regard to age at onset of the first psychotic symptom. Age at onset of the first
      psychotic symptom did not differ between the sexes regardless of whether
      schizophrenia was diagnosed by DSM-IV or by several alternative systems. Age at
      onset defined by other criteria, namely age at first contact with a physician,
      and age at first admission for psychiatric care, also did not show any
      differences between the sexes. Survival analysis of subjects having a documented
      date of birth revealed a female preponderance at younger ages. A higher positive
      symptom score predicted older age at onset of the first psychotic symptom in the
      total sample. These findings call into question the universality of the
      traditional view of a younger age at onset of schizophrenia among males.
      Tentative neurodevelopmental and cultural explanations are presented to explain
      why there is no sex difference in age at onset of schizophrenia in India.

PMID- 9611082
TI  - Lack of continuity--a problem in the care of young suicides.
AB  - The course of the psychiatric in-patient treatment received by 34 young people
      aged 15-24 years before their deaths from suicide was studied retrospectively on
      the basis of medical records. The quality of the care that they were given was
      appraised in terms of continuity, an important aspect of the care of young
      individuals during a period of dynamic development. There were two suicides among
      patients in child psychiatric care and 32 suicides among those in adult
      psychiatric care. Continuity of child psychiatric care was satisfactory, while
      the striking discontinuity in adult psychiatric care, in terms of contacts with
      doctors, therapists and other staff, with from 3 to 30 different doctors being
      involved during the period of care, may have been a factor contributing to the
      suicidal outcome in these cases. In total, 20 of the 34 young people had reported
      previously known suicide attempts, and notes concerning suicidal communication
      were mentioned in all but three of the records, while in only three of the
      records had any form of suicide-risk assessment been noted at the last care
      session before the suicide. Information about the suicidal process was thus
      available for most of these records but, as a rule, suicidal analyses were
      nevertheless lacking.

PMID- 9611083
TI  - The dimensionality of schizophrenia concepts in first-episode psychosis.
AB  - This study aimed to determine the dimensionality of concepts of schizophrenia
      using 11 different diagnostic systems, and then to identify the nature of these
      dimensions by their relationship to a range of signs and symptoms. The sample
      consisted of 479 patients admitted with a first episode of functional psychosis.
      The underlying structure of the 11 diagnostic systems was best represented by an
      oblique 3-factor solution. Whereas the second and third factors could be
      meaningfully interpreted by their correlations with signs and symptoms, the first
      factor, anchored by 'modern' nosologies such as DSM-III-R, was more clearly
      specified by what it is not (the absence of affective symptoms) rather than by
      what it is (the presence of characteristic psychotic symptoms). A logistic
      regression of DSM-III-R diagnosis on to separate diagnostic components supports
      the contention that duration of illness and affective exclusion criteria
      discriminate the presence of DSM-III-R schizophrenia much better than the three
      characteristic psychotic symptom groupings.

PMID- 9611084
TI  - Anticipation and imprinting in Spanish families with schizophrenia.
AB  - Evidence of imprinting and anticipation, two genetic phenomena that are
      correlated with clinical sequelae, was assessed in familial schizophrenia. A
      sample of patients (n=291) who fulfilled the ICD-9 criteria for schizophrenia and
      corresponding to the familial-type and sporadic-type of the disorder was
      recruited. Clinical anticipation and imprinting variables such as age at onset
      (AAO), schizophrenia subtype, course of disease and onset type were assessed over
      parental (G1) and filial (G2) generations in both schizophrenia types.
      Anticipation assessment indicated significant differences in mean AAO between
      parent-offspring pairs in unilineal families. These differences were not
      explained by a cohort effect. Imprinting assessment indicated non-significant
      differences in AAO between the offspring of affected mothers and the offspring of
      affected fathers. The results obtained for other clinical variables were non
      conclusive. The results suggest that anticipation, but not imprinting, is
      operative in schizophrenia.

PMID- 9611085
TI  - Cognitive deficits in schizophrenia and affective disorders: evidence for a final
      common pathway disorder.
AB  - This study was designed to determine whether patients with schizophrenia and
      those with affective disorders display a common pattern of cognitive deficits.
      Cognitive performance was assessed with a neuropsychological test battery in
      consecutively admitted in-patients with schizophrenia (n=100) and affective
      disorders (n=100). The two groups of patients showed a similar pattern of
      cognitive deficits, especially in tests focusing on attentional capacities. The
      groups only differed significantly in their performance on the Wisconsin Card
      Sorting Test (WCST), with the schizophrenic patients performing less well. These
      results suggest that, with the exception of the deficit as measured by the WCST,
      similar cognitive impairments exist in schizophrenia and affective disorders,
      even at very early stages of the illness. Therefore, patients with schizophrenia
      and those with affective disorders cannot be qualitatively distinguished with
      sufficient reliability. We postulate that the cognitive deficit pattern
      represents a final common pathway disorder in the two groups of patients.

PMID- 9611086
TI  - Impact of a history of physical and sexual abuse in eating disordered and
      asymptomatic subjects.
AB  - The present study aimed to explore the impact of sexual and/or physical abuse
      among eating disordered patients (ED) and asymptomatic subjects. A total of 86
      patients with anorexia nervosa, 69 patients with bulimia nervosa and 81
      asymptomatic subjects were assessed. Among ED, we did not find a significant
      association between abuse experiences and the severity of the eating disorder, or
      between abuse and dissociative symptoms. Among ED, self-destructive behaviour
      appears to be the most important predictor of a history of sexual and/or physical
      abuse. In contrast, in the asymptomatic group, the score on the Dissociation
      Questionnaire is the only significant predictor of reported abuse experiences.

PMID- 9611087
TI  - Eye movements in patients with schizophrenia: visual stimuli, semantic content
      and psychiatric symptoms.
AB  - In order to explore a possible association between psychiatric symptoms and eye
      movements, 32 patients with schizophrenia were examined using an eye mark
      recorder in combination with the Positive and Negative Syndrome Scale, and were
      compared with 32 controls. Four types of figures were presented to the subjects:
      geometrical figures, drawings, story drawings, and sentences. Mean eye fixation
      time was significantly longer and mean eye scanning length was significantly
      shorter for the patients than for controls, not only in response to the geometric
      figures, but also in response to the story drawings. Eye fixation time and
      scanning velocity were positively correlated with degrees of thought disturbance.
      The number of eye fixations, eye fixation time and scanning velocity were
      negatively correlated with degree of depressive tendency.

PMID- 9611088
TI  - Serotonergic 'vulnerability' in affective disorder: a study of the tryptophan
      depletion test and relationships between peripheral and central serotonin indexes
      in citalopram-responders.
AB  - A double-blind study of the tryptophan depletion (TD) challenge was performed on
      a sample consisting of 20 patients with a major depressive disorder in clinical
      remission after citalopram treatment. TD was induced by the intake of 43 g of an
      amino acid mixture containing the five large neutral amino acids. The control
      group received the same mixture, to which 2.3 g tryptophan had been added. Five
      of the 12 challenged patients showed a worsening of depressive symptoms during
      the day of the test. In contrast, there was no mood alteration in the eight
      control patients. Baseline cortisol levels were significantly higher in
      responders to TD compared to those in non-responders and controls. Platelet
      serotonin-receptor function and plasma prolactin levels were correlated. There
      was a significant positive correlation in the baseline data between rated mood
      state and plasma cortisol and a significant inverse correlation between related
      mood state and plasma tryptophan concentration. Thus low mood appeared to be
      associated with low serotonin precursor availability as well as with high
      cortisol levels.

PMID- 9611089
TI  - Perinatal complications, genetic risk and schizophrenia.

PMID- 9611090
TI  - Comparison of venlafaxine and imipramine in depressive illness.

PMID- 9611091
TI  - Higher-order chromatin structure-dependent repair of DNA double-strand breaks:
      factors affecting elution of DNA from nucleoids.
AB  - The nuclear matrix is increasingly identified with the processing of DNA damage.
      Previous work has suggested that association of DNA with the matrix can influence
      the repair of DNA double-strand breaks (DSBs) and the sensitivity of mammalian
      cells to ionizing radiation. By selectively examining DSBs that occur as
      multiples (multiple DSBs) within looped DNA structures, we have identified a
      subset of DSBs that repair with slow kinetics through the V(D)J recombination
      associated DSB repair pathway. Enrichment of S-phase populations by centrifugal
      elutriation and selective examination of nascent DNA by pulse-labeling were used
      to demonstrate that elution of DNA from nucleoids is retarded by the presence of
      replicating DNA. Previously, application of a Poisson-based model of induction of
      multiple DSBs and DNA elution to a panel of mammalian cell lines indicated that
      the size of the looped chromatin domains varied between cell lines. The data
      presented here explain the range in domain sizes between cells as the result of
      differences in the percentage of cells actively replicating their DNA. Correction
      of the model to account for S-phase populations results in a looped domain size
      of 2.9 Mbp independent of cell type. Single-cell gel electrophoresis of nucleoids
      provides additional evidence for such sized structures. Stabilization of DNA to
      elution during S phase does not permit repair of DSBs in the DSB repair mutants
      xrs5 and St.SCID, both defective for the DSB repair pathway associated with V(D)J
      recombination.

PMID- 9611092
TI  - Radioprotection of cellular chromatin by the polyamines spermine and putrescine:
      preferential action against formation of DNA-protein crosslinks.
AB  - Spermine is an efficient radioprotector of plasmid or viral DNA and of viral
      minichromosomes by a mechanism involving radical scavenging and the induction of
      compaction and aggregation of DNA. Based on radioprotection of SV40
      minichromosomes at a lower spermine concentration than needed for SV40 DNA,
      Newton et al. (Radiat. Res. 145, 776-780, 1996) proposed that the differential
      concentration dependence could account for the greater radiosensitivity of open
      regions of cellular chromatin compared to bulk inactive chromatin at
      physiological levels of spermine. However, we recently reported that, whereas the
      effects of spermine on the formation of DNA double-strand breaks (DSBs) in
      dehistonized V79 cell DNA (nucleoids) were consistent with spermine-induced DNA
      compaction, spermine provided no radioprotection of native chromatin and only
      modest radioprotection of histone H1-depleted chromatin (Chiu and Oleinick,
      Radiat. Res. 148, 188-192, 1997). To further characterize the radioprotection of
      cellular chromatin by spermine, radiation-induced DNA-protein crosslinks (DPCs)
      were investigated, because of evidence that these lesions occur preferentially at
      or near the sites of anchorage of chromosomes to the nuclear matrix. In contrast
      to the relatively inefficient radioprotection of V79 cell chromatin against the
      formation of DSBs, low concentrations (<0.1 mM) of spermine or putrescine
      provided partial radioprotection against the formation of DPCs in both native and
      H1-depleted chromatin. Whereas all DPCs generated by the irradiation of
      chromatin, above the level generated in intact cells, could be blocked by 5 mM
      spermine, less than half could be blocked by 5 mM putrescine. The difference in
      efficiency of radioprotection of native chromatin by the two polyamines can be
      accounted for by assuming that the binding of spermine is 10 times as efficient
      as the binding of putrescine. The results suggest that (a) both spermine and
      putrescine bind preferentially and with high affinity at matrix-associated sites
      of formation of DPCs, disrupting the associations between DNA and protein that
      are essential for formation of DPCs and/or scavenging hydroxyl radicals at these
      sites; (b) a smaller fraction of the sites are susceptible to putrescine than to
      spermine; and (c) endogenous spermine is a major radioprotector of cells against
      the formation of DPCs, either because of specific features of the lesion or
      because of the site of lesion formation at the nuclear matrix.

PMID- 9611093
TI  - The limits to radioprotection of Chinese hamster V79 cells by WR-1065 under
      aerobic conditions.
AB  - Clonogenic survival and drug content for Chinese hamster V79-171 cells incubated
      in suspension with WR-1065 prior to gamma irradiation have been determined.
      Factors that might influence the radioprotection by WR-1065 were investigated in
      control studies. Intracellular drug levels studied ranged between 0-36 nmol per
      10(6) cells. In control studies, it was established that extracellular drug
      toxicity was not significant for cells in suspension at 10(6) per milliliter over
      short periods but was important when residual drug was present above 2 microM in
      the final plating of cells. Accumulation of intracellular drug above 30 nmol per
      10(6) cells produced significant cytotoxicity in unirradiated cells. Irradiation
      with doses as high as 150 Gy produced no significant change in the total drug
      level or the thiol/disulfide ratio, either for the drug in the cells or for the
      drug in the medium. Preirradiation with 8 Gy did not change the ability of cells
      to import the drug but did appear to increase the cytotoxicity of the
      intracellular drug at levels above 25 nmol per 10(6) cells. There was no
      qualitative difference in the ability of WR-1065 to protect viable cells
      preirradiated with 8 Gy compared with protection of unirradiated cells. For a
      given gamma-ray dose from 2 to 40 Gy, there is a limiting value for surviving
      fraction which cannot be increased by further elevation of the intracellular drug
      level in V79-171 cells. Such limiting radioprotection was demonstrated for HT
      29/SP-ld, HeLa, Me-180-VCII and OV-2008-VI human tumor cells.

PMID- 9611094
TI  - Detailed characterization of the 1087 MeV/nucleon iron-56 beam used for
      radiobiology at the alternating gradient synchrotron.
AB  - We report beam characterization and dosimetric measurements made using a 56Fe
      beam extracted from the Brookhaven National Laboratory Alternating Gradient
      Synchrotron (AGS) with a kinetic energy of 1087 MeV/nucleon. The measurements
      reveal that the depth-dose distribution of this beam differs significantly from
      that obtained with a 600 MeV/nucleon iron beam used in several earlier
      radiobiology experiments at the Lawrence Berkeley National Laboratory's BEVALAC.
      We present detailed measurements of beam parameters relevant for radiobiology,
      including track- and dose-averaged linear energy transfer (LET), fragment
      composition and LET spectra measured behind sample holders used in irradiations
      of biological samples. We also report measurements of fluence behind three depths
      (1.94, 4.68 and 9.35 g cm(-2)) of polyethylene targets with the 1087 MeV/nucleon
      beam, and behind 1.94 g cm(-2) of polyethylene with a 610 MeV/nucleon beam
      delivered by the AGS. These results are compared to earlier measurements with the
      600 MeV/nucleon beam at the BEVALAC.

PMID- 9611095
TI  - Induction of serum amyloid A inflammatory response genes in irradiated bone
      marrow cells.
AB  - The molecular mechanisms underlying radiation-induced defects in the bone marrow
      which may contribute to the development of radiation-induced hematopoietic
      disorders such as aplastic anemia and leukemia are not known. Persistent changes
      in gene expression were examined after exposure of cells of a murine bone marrow
      stromal cell line to ionizing radiation. Analysis of mRNA transcript levels by
      differential display led to the identification of a band, C122, which increased
      in abundance 1 week after exposure. Northern blot hybridization verified these
      results and revealed a 12-fold increase in abundance of this message for up to 3
      weeks after irradiation in vitro. DNA sequence analysis identified clone C122 as
      murine serum amyloid A 3 (Saa3), a member of the Saa family of acute-phase or
      inflammatory response genes. Saa message levels were then examined in vivo in the
      bone marrow of mice exposed to total-body irradiation. Semi-quantitative reverse
      transcription-polymerase chain reaction revealed a 15-20-fold increase in Saa3
      message levels in the bone marrow of irradiated mice from 3 days to 2 weeks after
      exposure. Saa3 message levels continued to be 2-3-fold above control for up to 28
      weeks in vivo. Two additional members of the murine Saa gene family, Saa1 and
      Saa2, were also detected in irradiated bone marrow. The expression of SAA1 and
      SAA2 was also detected in irradiated cells of human bone marrow stromal cell
      lines in vitro. These results suggest that SAA genes are involved in the
      radiation response in the bone marrow, but their role in the recovery of the
      marrow after irradiation or in the development of radiation-induced hematopoietic
      disorders remains to be established. Additionally, the persistent radiation
      induced increase in expression suggests the potential utility of using SAA3
      transcript levels as a molecular marker of past radiation exposure.

PMID- 9611096
TI  - Calcium-dependent stimulation of mitogen-activated protein kinase activity in
      A431 cells by low doses of ionizing radiation.
AB  - Ionizing radiation at 2 Gy activates the epidermal growth factor receptor (EGFR)
      kinase activity in A431 squamous carcinoma cells and as a consequence transiently
      activates a downstream effector, mitogen-activated protein kinase (MAPK). A dose
      response analysis shows fourfold activation 3-5 min after irradiation at 0.5 Gy
      with no additional activation after doses up to 4 Gy. Activation is independent
      of protein kinase C as defined by marginal effects of protein kinase C down
      regulation and the protein kinase C inhibitor, chelerythrine. In contrast, an
      intracellular Ca2+ chelator (BAPTA/AM), a Ca2+ antagonist (TMB-8) and a
      phospholipase C inhibitor (U73223), which inhibits radiation-induced Ca2+
      oscillations, all block MAPK stimulation. The upstream component, Raf-1, is also
      activated through a mechanism that is dependent on EGFR and Ca2+. Activation of
      Raf-1, monitored by tyrosine phosphorylation and co-immunoprecipitation with Ras,
      was inhibited by BAPTA/AM and TMB-8, indicating that the Ca2+-dependent step
      occurs at or before the interaction of Ras and Raf-1. Neither the Ras guanosine
      triphosphate exchange protein, SOS, nor Ca2+-activated tyrosine kinases linked to
      the MAPK pathway, focal adhesion kinase and PYK2, were stimulated by radiation.
      In contrast, EGF activated SOS as shown by the enhanced association of SOS with
      EGFR in co-immunoprecipitation experiments. These results suggest that activation
      of EGFR-dependent downstream signaling induced by radiation differs from that
      induced by the natural ligands of EGFR.

PMID- 9611097
TI  - Radiation-induced apoptosis in human lymphocytes and lymphoma cells critically
      relies on the up-regulation of CD95/Fas/APO-1 ligand.
AB  - Ionizing radiation is known to induce death by apoptosis in malignant and
      nonmalignant human lymphocytes. The mechanism which initiates the induction of
      apoptosis has not been identified. Here we demonstrate that a radiation-induced
      up-regulation of CD95/Fas/APO-1 ligand (CD95-L) is involved in the induction of
      apoptosis in lymphocytes and lymphoma cells. Using antibodies against CD95-L, we
      detected a rapid and persistent up-regulation of CD95-L in Jurkat cells and blood
      lymphocytes after irradiation. Blocking of interactions between CD95/Fas/APO-1
      and CD95-L with inhibitory antibodies reduces apoptosis after irradiation. The
      hypothesis that an interaction between CD95 and CD95-L is involved in radiation
      induced apoptosis is supported by the finding that only peripheral blood
      lymphocytes that are stimulated with interleukin 2 for 5 days and thus are
      rendered sensitive to CD95-L show pronounced levels of apoptosis in response to
      low radiation doses, whereas resting peripheral blood lymphocytes show very low
      levels of apoptosis after treatment with CD95-L and radiation. The finding that
      the caspase FLICE is degraded proteolytically after irradiation and the
      observation of a radiation-induced CD95 receptor capping confirm the functional
      activation of the CD95 receptor.

PMID- 9611098
TI  - Impaired regulation of nuclear factor-kappaB results in apoptosis induced by
      gamma radiation.
AB  - Recent studies have shown that activation of nuclear factor-kappaB (NF-kappaB) is
      critical for cell survival. Cells from patients with ataxia telangiectasia (AT)
      have an impaired NF-kappaB response to ionizing radiation. AT cells also exhibit
      inappropriate regulation of apoptosis. We report here that expression of a
      dominant negative form of IkappaB-alpha, an inhibitor of NF-kappaB, protects AT
      fibroblasts from apoptosis induced by gamma radiation, but it enhances apoptosis
      in normal fibroblasts. Furthermore, the process leading to apoptosis may involve
      caspase 3-mediated cleavage of IkappaB-alpha. These data suggest that regulation
      of NF-kappaB may play an important role in programmed cell death induced by DNA
      damage in AT cells.

PMID- 9611099
TI  - Persistence of radiation-induced translocations in human peripheral blood
      determined by chromosome painting.
AB  - We have investigated the persistence of translocations and other types of
      chromosome damage with time using human peripheral blood acutely exposed in vitro
      to 137Cs gamma rays at doses ranging from 0.5 to 4 Gy. Freshly drawn blood from
      one donor was irradiated and metaphase chromosomes were prepared 2 to 7 days
      after exposure. Chromosomes 1, 2 and 4 were painted red-orange and chromosomes 3,
      5 and 6 were painted green by fluorescence in situ hybridization (FISH) using
      "semi-directly" labeled whole-chromosome painting probes. This type of labeling
      combines direct and indirect labeling and showed significant advantages over both
      these other methods. All types of structural chromosome aberrations were
      classified by the Protocol for Aberration Identification and Nomenclature
      Terminology (PAINT) system. The yields of dicentric chromosomes, acentric
      fragments and ring chromosomes diminished with time as expected. Translocations
      exhibited greater persistence but showed a clear and statistically significant
      reduction in frequency at all doses. The mathematical model suggested that the
      translocation frequencies would reach a plateau of approximately 4, 15, 51, 106
      and 179 translocations per 100 cell equivalents after irradiation with 0.5, 1, 2,
      3 and 4 Gy, respectively. When translocations were classified by the conventional
      system, an analysis of the distribution of translocations and dicentrics per cell
      indicated that both types of exchanges were Poisson-distributed 48 h
      postirradiation. However, cells bearing translocations have a higher possibility
      of having dicentrics than cells without translocations. These findings suggest
      that dicentrics may contribute to a decline of translocation frequencies with
      time, and that some translocations are not completely persistent. The results
      obtained here using human blood exposed in vitro may influence the use of
      translocations as a retrospective biodosimeter of exposure to ionizing radiation
      in humans.

PMID- 9611100
TI  - Radiation therapy among atomic bomb survivors, Hiroshima and Nagasaki.
AB  - As a follow-up to the two previous surveys of radiation therapy among the atomic
      bomb survivors, a large-scale survey was performed to document (1) the number of
      radiation therapy treatments received by the atomic bomb survivors and (2) the
      types of radiation treatments conducted in Hiroshima and Nagasaki. The previous
      two surveys covered the radiation treatments among the Radiation Effects Research
      Foundation Adult Health Study (AHS) population, which is composed of 20,000
      persons. In the present survey, the population was expanded to include the Life
      Span Study (LSS), including 93,611 atomic bomb survivors and 26,517 Hiroshima and
      Nagasaki citizens who were not in the cities at the times of the bombings. The
      LSS population includes the AHS population. The survey was conducted from 1981 to
      1984. The survey teams reviewed all the medical records for radiation treatments
      of 24,266 patients at 11 large hospitals in Hiroshima and Nagasaki. Among them,
      the medical records for radiation treatments of 1556 LSS members were reviewed in
      detail. By analyzing the data obtained in the present and previous surveys, the
      number of patients receiving radiation therapy was estimated to be 4501 (3.7%) in
      the LSS population and 1026 (5.1%) in the AHS population between 1945-1980.
      During 1945-1965, 98% of radiation treatments used medium-voltage X rays, and 66%
      of the treatments were for benign diseases. During 1966-1980, 94% of the
      radiation treatments were for malignant neoplasms. During this period, 60Co gamma
      ray exposure apparatus and high-energy electron accelerators were the prevalent
      mode of treatment in Hiroshima and in Nagasaki, respectively. The mean frequency
      of radiation therapy among the LSS population was estimated to have been 158
      courses/year during 1945-1965 and 110 courses/year during 1966-1980. The present
      survey revealed that 377 AHS members received radiation therapy. The number was
      approximately twice the total number of cases found in the previous two surveys.
      Thus the data on radiation therapy in the AHS members have been updated well by
      this survey, and will provide information for more precise dose-response analyses
      of radiation effects in the AHS population. The information extracted from the
      medical records of the hospitals consisted of hospital names, treatment periods,
      body sites treated, diagnoses, treatment doses, radiation sources, the field
      sizes of the exposures and the data for identification of the patients. These
      data will be essential in estimating the organ doses from scattered radiation and
      in evaluating the effects of therapeutic radiation.

PMID- 9611102
TI  - Anti-emetic effect of ondansetron and granisetron after exposure to mixed neutron
      and gamma irradiation.
AB  - The anti-emetic efficiency of orally administered ondansetron and granisetron has
      been tested in macaques exposed to a mixed y and neutron radiation (6 Gy) with a
      high neutron/gamma-ray ratio. Our experiments reveal that a single delivery of
      ondansetron (1 or 2 mg kg(-1)) or of granisetron (0.25 mg kg(-1)) 45-90 min
      before irradiation or 35-45 min after irradiation was not totally effective.
      Conversely, the delivery of two doses with the same delay prior to and after
      exposure led to a complete prevention of vomiting and retching. These
      observations can be explained by the dual mechanism of radiation-induced emesis:
      an early peripheral mechanism and a later central mechanism. Two deliveries of 5
      HT3 receptor antagonists seem to disrupt serotonergic transmission at the brain
      stem structures and to affect the peripheral release of serotonin from the gut,
      thus completely preventing radiation-induced vomiting. This study confirms that
      the 5-HT3-dependent mechanisms that mediate emesis are similar for both neutron
      and gamma radiation.

PMID- 9611101
TI  - Salivary gland tumors after childhood radiation treatment for benign conditions
      of the head and neck: dose-response relationships.
AB  - We have investigated the dose-response relationships for the incidence of
      salivary gland tumors in a cohort of 2945 individuals who were irradiated as
      children between 1939-1962. Most of the patients were treated to reduce the size
      of their tonsils and adenoids. The mean dose to the salivary glands (+/-SD) was
      4.2 +/- 1.7 Gy. Eighty-nine patients developed 91 salivary gland neoplasms; 22
      had single malignancies, 64 had single benign neoplasms, 2 developed two separate
      benign neoplasms, and 1 developed a single neoplasm but did not have surgery. The
      majority (81 of 89) of the patients developed neoplasms in the parotid glands.
      Mucoepidermoid carcinomas were the most common malignancy and mixed (pleomorphic)
      adenomas were the most common benign neoplasm. For all salivary gland tumors, the
      excess relative risk per gray (ERR/Gy) was 0.82; however, the 95% confidence
      interval was wide (0.04, upper bound indeterminate). The trend was determined
      principally by benign tumors, as there was no dose-response relationship for
      salivary gland cancer, although there were too few cases to draw definitive
      conclusions. Overall, our study provides support for an association between
      salivary gland tumors and radiation exposure. Although most salivary gland tumors
      are benign and are usually readily detected, they may cause morbidity, and people
      who have been irradiated in the area should be monitored for their occurrence.

PMID- 9611103
TI  - DNA damage in rat brain cells after in vivo exposure to 2450 MHz electromagnetic
      radiation and various methods of euthanasia.
AB  - The present study was done to confirm the reported observation that low-intensity
      acute exposure to 2450 MHz radiation causes DNA single-strand breaks (Lai and
      Singh, Bioelectromagnetics 16, 207-210, 1995). Male Sprague-Dawley rats weighing
      approximately 250 g were irradiated with 2450 MHz continuous-wave (CW) microwaves
      for 2 h at a specific absorption rate of 1.2 W/kg in a cylindrical waveguide
      system (Guy et al., Radio Sci. 14, 63-74, 1979). There was no associated rise in
      the core body temperature of the rats. After the irradiation or sham treatments,
      rats were euthanized by either CO2 asphyxia or decapitation by guillotine (eight
      pairs of animals per euthanasia group). After euthanasia the brains were removed
      and immediately immersed in cold Ames medium and the cells of the cerebral cortex
      and the hippocampus were dissociated separately and subjected to the alkaline
      comet assay. Irrespective of whether the rats were euthanized by CO2 asphyxia or
      decapitated by guillotine, no significant differences were observed between
      either the comet length or the normalized comet moment of cells from either the
      cerebral cortex or the hippocampus of sham-treated rats and those from the
      irradiated rats. However, the data for the rats asphyxiated with CO2 showed more
      intrinsic DNA damage and more experiment-to-experiment variation than did the
      data for rats euthanized by guillotine. Therefore, the guillotine method of
      euthanasia is the most appropriate in studies relating to DNA damage.
      Furthermore, we did not confirm the observation that DNA damage is produced in
      cells of the rat cerebral cortex or the hippocampus after a 2-h exposure to 2450
      MHz CW microwaves or at 4 h after the exposure.

PMID- 9611104
TI  - The minimum Do for cell killing for alpha-particle emitters uniformly distributed
      in an extended medium.
AB  - For cells irradiated by alpha particles in suspension, there is presently no
      simple test to show that the cell killing can be attributed to alpha-particle
      passages through the nuclei. In this communication, for a uniform distribution of
      alpha-particle sources and spherical nuclei, a D0 is calculated such that at
      least 63% of the cell nuclei have at least one alpha-particle passage. For a
      uniform distribution of alpha-particle sources and spherical nuclei, it is shown
      that the average dose for 63% of the cell nuclei to be hit (37% not hit) is equal
      to the average dose per hit. For this condition an energy deposition of any size
      would result in cell death and the average dose is the minimum D0 possible.
      Minimum D0 values are calculated using a Monte Carlo treatment for nuclear
      diameters from 4 to 10 microm and initial alpha-particle energies between 3.18
      and 8.38 MeV.

PMID- 9611105
TI  - Enhanced neoplastic transformation in an inhomogeneous radiation field: an effect
      of the presence of heavily damaged cells: a critical appraisal.

PMID- 9611106
TI  - Enhanced neoplastic transformation in an inhomogeneous radiation field: an effect
      of exposure to supralethally damaged cells.

PMID- 9611120
TI  - Glucagon-mediated Ca2+ signaling in BHK cells expressing cloned human glucagon
      receptors.
AB  - From video imaging of fura 2-loaded baby hamster kidney (BHK) cells stably
      expressing the cloned human glucagon receptor, we found the Ca2+ response to
      glucagon to be specific, dose dependent, synchronous, sensitive to pertussis
      toxin, and independent of Ca2+ influx. Forskolin did not elicit a Ca2+ response,
      but treatment with a protein kinase A inhibitor, the Rp diastereomer of 8
      bromoadenosine-3',5'-cyclic monophosphothioate, resulted in a reduced glucagon
      mediated Ca2+ response as well as Ca2+ oscillations. The specific phospholipase C
      inhibitor U-73122 abolished the Ca2+ response to glucagon, and a modest twofold
      increase in inositol trisphosphate (IP3) production could be observed after
      stimulation with glucagon. In BHK cells coexpressing glucagon and muscarinic (M1)
      acetylcholine receptors, carbachol blocked the rise in intracellular free Ca2+
      concentrations in response to glucagon, whereas glucagon did not affect the
      carbachol-induced increase in Ca2+. Furthermore, carbachol, but not glucagon,
      could block thapsigargin-activated increases in intracellular free Ca2+
      concentration. These results indicate that, in BHK cells, glucagon receptors can
      activate not only adenylate cyclase but also a second independent G protein
      coupled pathway that leads to the stimulation of phospholipase C and the release
      of Ca2+ from IP3-sensitive intracellular Ca2+ stores. Finally, we provide
      evidence to suggest that cAMP potentiates the IP3-mediated effects on
      intracellular Ca2+ handling.

PMID- 9611121
TI  - Dynamics of myosin light chain phosphorylation at Ser19 and Thr18/Ser19 in smooth
      muscle cells in culture.
AB  - Using the specific antibodies pLC1 and pLC2 for mono- and diphosphorylated 20-kDa
      myosin light chain (MLC20) at Ser19 and at both Thr18 and Ser19, respectively, we
      visualized the dynamics of the MLC20 phosphorylation in rabbit aortic smooth
      muscle cells (cell line SM-3) stimulated with PGF2alpha. In the resting state,
      the diphosphorylated form was located in the peripheral region of the cell, such
      as the leading edge or the adhesion plaque, and the monophosphorylated form was
      located not only in the peripheral region but also on a discontinuous fibrillary
      structure along the long axis of the cell. After stimulation with 30 microM
      PGF2alpha, although localization of the monophosphorylated form changed little,
      the content of the diphosphorylated form increased and the distribution spread
      along the fibrillary structure to an extent the same as or similar to that of the
      monophosphorylated form, which colocalized with actin filament bundles. The
      diphosphorylation of MLC20 was more sensitive to protein kinase inhibitors, HA
      1077, HA-1100, staurosporine, wortmannin, and ML-9, than was the
      monophosphorylation. In light of these observations, we propose that MLC20
      diphosphorylation and monophosphorylation are regulated by different mechanisms.

PMID- 9611122
TI  - Growth factor-like action of lysophosphatidic acid on human B lymphoblasts.
AB  - Proliferation and immunoglobulin secretion of B lymphocytes are regulated by
      specific antigens and numerous accessory immunomodulatory factors.
      Lysophosphatidic acid (LPA) is a glycerophospholipid mediator that is released
      from activated blood platelets, attains high levels in serum, and exerts potent
      stimulatory effects on, e.g., neutrophils, monocytes, and T lymphocytes. LPA is
      also generated by a secretory, cytokine-inducible phospholipase A2 present in
      high concentrations in inflammatory exudates and septic states. We investigated
      effects of LPA on human Epstein-Barr virus-immortalized B lymphoblasts, a model
      for immunoglobulin-secreting B cells. Intracellular Ca2+ was determined with fura
      2 and the formation of inositol 1,4, 5-trisphosphate by anion-exchange
      chromatography. LPA stimulated an increase in inositol 1,4,5-trisphosphate levels
      and induced a transient rise in intracellular free Ca2+ concentration from 105 +/
      17 to 226 +/- 21 nM. This Ca2+ signal resulted from Ca2+ mobilization and Ca2+
      influx and was subject to homologous desensitization. Pertussis toxin inhibited
      these responses by approximately 70%. Furthermore, LPA stimulated a 27.5%
      increase in guanosine 5'-O-(3-thiotriphosphate) binding to permeabilized B
      lymphoblasts, which suggests the direct activation of pertussis toxin-sensitive G
      proteins by LPA. LPA stimulated a strong increase in the specific phosphorylation
      of the mitogen-activated protein kinase (immunoblot analysis) that was prevented
      by the MEK inhibitor PD-98059. Finally, LPA triggered a 2-fold increase in DNA
      synthesis ([3H]thymidine incorporation) and a 2-fold increase in B lymphoblast
      number and evoked a 20- to 50-fold increase in immunoglobulin formation. By RT
      PCR we detected specific mRNA transcripts for the recently cloned human LPA
      receptor. Thus our data suggest that LPA behaves as a B cell growth factor.

PMID- 9611123
TI  - Endothelin-1 activates phospholipases and channels at similar concentrations in
      porcine coronary arteries.
AB  - Sensitivity of endothelin-1 (ET-1)-ion channel interactions has been proposed to
      exceed that of ET-1-phospholipase activation in vascular smooth muscle. We wanted
      to determine whether short-circuiting ion channels with staphylococcal alpha
      toxin pores would shift the ET-1-force relation to the right as predicted from
      the above proposal. Medium size porcine coronary arteries (outer diameter 0.7-1.5
      mm) were mounted on isometric force transducers. ET-1 concentration response
      curves were compared between intact rings and those subjected to alpha-toxin
      treatment with Ca buffered at 0.1 microM. The EC50 for treated rings (1.5 +/- 1.0
      nM, n = 5 pigs) was similar to that for intact rings (1.9 +/- 0.4 nM). The Ca
      sensitivity of the alpha-toxin-treated rings (EC50 = 0.43 +/- 0.08 microM) was
      similar to that reported by other laboratories for intact and alpha-toxin-treated
      arteries and was shifted eightfold to the left by a high concentration of ET-1
      (10 nM). Measurements of [32P]phosphatidic acid ([32P]PA) levels were used to
      evaluate phospholipase activity in intact arteries. The time courses for [32P]PA
      production and contraction were similar in response to high (100 nM) and to low
      (1 nM) ET-1. Significant increases in both steady-state contraction and [32P]PA
      occurred over a wide range of ET-1 concentrations tested (0.3-100 nM). Our
      findings support the concept that ET-1-phospholipase coupling is operative over
      the whole concentration range that induces contractile responses. It is suggested
      that both Ca entry and Ca sensitization processes are activated by ET-1 at low
      concentrations (<EC50) and that both processes contribute significantly to the
      integrated response.

PMID- 9611124
TI  - Release of dopamine and norepinephrine by hypoxia from PC-12 cells.
AB  - We examined the effects of hypoxia on the release of dopamine (DA) and
      norepinephrine (NE) from rat pheochromocytoma 12 (PC-12) cells and assessed the
      involvement of Ca2+ and protein kinases in stimulus-secretion coupling.
      Catecholamine release was monitored by microvoltammetry using a carbon fiber
      electrode as well as by HPLC coupled with electrochemical detection (ECD).
      Microvoltammetric analysis showed that hypoxia-induced catecholamine secretion
      (PO2 of medium approximately 40 mmHg) occurred within 1 min after the onset of
      the stimulus and reached a plateau between 10 and 15 min. HPLC-ECD analysis
      revealed that, at any level of PO2, the release of NE was greater than the
      release of DA. In contrast, in response to K+ (80 mM), DA release was
      approximately 11-fold greater than NE release. The magnitude of hypoxia-induced
      NE and DA releases depended on the passage, source, and culture conditions of the
      PC-12 cells. Omission of extracellular Ca2+ or addition of voltage-gated Ca2+
      channel blockers attenuated hypoxia-induced release of both DA and NE to a
      similar extent. Protein kinase inhibitors, staurosporine (200 nM) and
      bisindolylmaleimide I (2 microM), on the other hand, attenuated hypoxia-induced
      NE release more than DA release. However, protein kinase inhibitors had no
      significant effect on K+-induced NE and DA releases. These results demonstrate
      that hypoxia releases catecholamines from PC-12 cells and that, for a given
      change in PO2, NE release is greater than DA release. It is suggested that
      protein kinases are involved in the enhanced release of NE during hypoxia.

PMID- 9611125
TI  - Length-dependent modulation of smooth muscle activation: effects of agonist,
      cytochalasin, and temperature.
AB  - We tested the hypothesis that mechanical strain modulates agonist sensitivity of
      smooth muscle by measuring myosin phosphorylation and contractile force in bovine
      tracheal smooth muscle activated by various concentrations of the muscarinic
      receptor agonist carbachol and at various muscle lengths. Increasing carbachol
      concentration by 10,000-fold did not restore myosin phosphorylation levels at
      shorter muscle lengths to the level at optimal length (Lo). Maximum levels of
      myosin phosphorylation induced by carbachol at 0.6, 0.8, and 1.0 Lo were similar
      but became lower at <0.6 Lo. Cytochalasin D significantly attenuated carbachol
      induced contraction by 54%. In addition, cytochalasin D treatment induced a
      parallel downward shift in the length-myosin phosphorylation relation. Lowering
      temperature from 37 to 23 degrees C did not significantly change the length
      dependencies of carbachol-induced active force and myosin phosphorylation. These
      results have led us to conclude that 1) agonist sensitivity and maximum level of
      activation (as measured by myosin phosphorylation) are targets of length
      dependent modulation, 2) actin filaments involved in contraction and length
      dependent modulation are distinct in sensitivity to cytochalasin D, and 3) length
      dependent modulation is relatively temperature insensitive.

PMID- 9611126
TI  - Determinants of relaxation rate in skinned frog skeletal muscle fibers.
AB  - The influences of sarcomere uniformity and Ca2+ concentration on the kinetics of
      relaxation were examined in skinned frog skeletal muscle fibers induced to relax
      by rapid sequestration of Ca2+ by the photolysis of the Ca2+ chelator, diazo-2,
      at 10 degreesC. Compared with an intact fiber, diazo-2-induced relaxation
      exhibited a faster and shorter initial slow phase and a fast phase with a longer
      tail. Stabilization of the sarcomeres by repeated releases and restretches during
      force development increased the duration of the slow phase and slowed its
      kinetics. When force of contraction was decreased by lowering the Ca2+
      concentration, the overall kinetics of relaxation was accelerated, with the slow
      phase being the most sensitive to Ca2+ concentration. Twitchlike contractions
      were induced by photorelease of Ca2+ from a caged Ca2+ (DM-Nitrophen), with
      subsequent Ca2+ sequestration by intact sarcoplasmic reticulum or Ca2+ rebinding
      to caged Ca2+. These twitchlike responses exhibited relaxation kinetics that were
      about twofold slower than those observed in intact fibers. Results suggest that
      the slow phase of relaxation is influenced by the degree of sarcomere homogeneity
      and rate of Ca2+ dissociation from thin filaments. The fast phase of relaxation
      is in part determined by the level of Ca2+ activation.

PMID- 9611127
TI  - Glutamate transport and cellular glutamine metabolism: regulation in LLC-PK1 vs.
      LLC-PK1-F+ cell lines.
AB  - The glutamate (Glu) transporter may modulate cellular glutamine (Gln) metabolism
      by regulating both the rates of hydrolysis and subsequent conversion of Glu to
      alpha-ketoglutarate and NH+4. By delivering Glu, a competitive inhibitor of Gln
      for the phosphate-dependent glutaminase (PDG) as well as an acid-load activator
      of glutamate dehydrogenase (GDH) flux, the transporter may effectively substitute
      extracellularly generated Glu from the gamma-glutamyltransferase for that derived
      intracellularly from Gln. We tested this hypothesis in two closely related
      porcine kidney cell lines, LLC-PK1 and LLC-PK1-F+, the latter selected to grow in
      the absence of glucose, relying on Gln as their sole energy source. Both cell
      lines exhibited PDG suppression as the result of Glu uptake while disrupting the
      extracellular L-Glu uptake, with D-aspartate-accelerated intracellular Glu
      formation coupled primarily to the ammoniagenic pathway (GDH). Conversely,
      enhancing the extracellular Glu formation with p-aminohippurate and Glu uptake
      suppressed intracellular Gln hydrolysis while NH+4 formation from Glu increased.
      Thus these results are consistent with the transporter's dual role in modulating
      both PDG and GDH flux. Interestingly, PDG flux was actually higher in the Gln
      adapted LLC-PK1-F+ cell line because of a two- to threefold enhancement in Gln
      uptake despite greater Glu uptake than in the parental LLC-PK1 cells, revealing
      the importance of both Glu and Gln transport in the modulation of PDG flux.
      Nevertheless, when studied at physiological Gln concentration, PDG flux falls
      under tight Glu transporter control as Gln uptake decreases, suggesting that
      cellular Gln metabolism may indeed be under Glu transporter control in vivo.

PMID- 9611128
TI  - Na+/Ca2+ exchange in catfish retina horizontal cells: regulation of intracellular
      Ca2+ store function.
AB  - The role of the Na+/Ca2+ exchanger in intracellular Ca2+ regulation was
      investigated in freshly dissociated catfish retinal horizontal cells (HC). Ca2+
      permeable glutamate receptors and L-type Ca2+ channels as well as inositol 1,4,5
      trisphosphate-sensitive and caffeine-sensitive intracellular Ca2+ stores regulate
      intracellular Ca2+ in these cells. We used the Ca2+-sensitive dye fluo 3 to
      measure changes in intracellular Ca2+ concentration ([Ca2+]i) under conditions in
      which Na+/Ca2+ exchange was altered. In addition, the role of the Na+/Ca2+
      exchanger in the refilling of the caffeine-sensitive Ca2+ store following
      caffeine-stimulated Ca2+ release was assessed. Brief applications of caffeine (1
      10 s) produced rapid and transient changes in [Ca2+]i. Repeated applications of
      caffeine produced smaller Ca2+ transients until no further Ca2+ was released.
      Store refilling occurred within 1-2 min and required extracellular Ca2+. Ouabain
      induced increases in intracellular Na+ concentration ([Na+]i) increased both
      basal free [Ca2+]i and caffeine-stimulated Ca2+ release. Reduction of external
      Na+ concentration ([Na+]o) further and reversibly increased [Ca2+]i in ouabain
      treated HC. This effect was not abolished by the Ca2+ channel blocker nifedipine,
      suggesting that increases in [Na+]i promote net extracellular Ca2+ influx through
      a Na+/Ca2+ exchanger. Moreover, when [Na+]o was replaced by Li+, caffeine did not
      stimulate release of Ca2+ from the caffeine-sensitive store after Ca2+ depletion.
      The Na+/Ca2+ exchanger inhibitor 2',4'-dimethylbenzamil significantly reduced the
      caffeine-evoked Ca2+ response 1 and 2 min after store depletion.

PMID- 9611130
TI  - Androgen receptors in human preadipocytes and adipocytes: regional specificities
      and regulation by sex steroids.
AB  - Various clinical and epidemiological evidence strongly suggests a major role for
      sex steroid hormones in the determination of anatomical specificities of fat
      distribution in human. To date, no studies have examined the possible presence of
      androgen receptors (AR) in human adipocytes and preadipocytes. We have studied AR
      in preadipocytes from various anatomical locations (intra-abdominal and
      subcutaneous) in middle-aged men and women during the proliferation and
      differentiation processes (adipogenesis). Androgen binding sites quantified by
      [3H]R-1881-specific binding in whole cell extracts were twofold higher in intra
      abdominal than in subcutaneous preadipocytes but identical for the same fat
      depots in men and women. Western blot analysis revealed 1) the presence of AR in
      the nuclear and cytosolic fractions of human preadipocytes, 2) a decrease of AR
      expression during adipogenesis, and 3) an upregulation of AR by androgens in
      vitro. RT-PCR experiments showed the presence of AR mRNA in human preadipocytes
      and adipocytes and also the regional specificity of AR distribution. However, AR
      mRNA expression was found to increase during adipogenesis. The same results were
      observed in rat preadipocytes. In conclusion, this study clearly demonstrates the
      presence of AR in human preadipocytes and adipocytes and suggests that androgens
      may contribute, through regulation of their own receptors, to the control of
      adipose tissue development.

PMID- 9611129
TI  - ICAM-1-CD18 interaction mediates neutrophil cytotoxicity through protease
      release.
AB  - Interaction of the beta2-integrin complex on the polymorphonuclear neutrophil
      (PMN) with intercellular adhesion molecule-1 (ICAM-1) has been implicated in PMN
      mediated cytotoxicity. This study examined interaction of the CD11a, CD11b, and
      CD18 subunits of the beta2-integrin with ICAM-1, transfected into Chinese hamster
      ovarian (CHO) cells to avoid effects of other adhesion molecules. Incubation of
      quiescent PMNs with wild-type and ICAM-1-transfected CHO cells produced nominal
      cell lysis. Similarly, when phorbol myristate acetate (PMA)-activated PMNs were
      incubated with wild-type CHO cells, minimal cytotoxicity was produced. However,
      when ICAM-1-transfected CHO cells were incubated with PMA-activated PMNs, 40%
      cell lysis occurred. Blockade with a monoclonal antibody (MAb) to ICAM-1 or MAbs
      to CD11a, CD11b, or CD18 reduced PMN-mediated cytotoxicity to baseline. To
      examine the role of adhesion in cytotoxicity, we studied beta2-integrin-mediated
      PMN adhesion to ICAM-1-transfected CHO cells and found that MAbs for CD11a,
      CD11b, and CD18 all abrogated PMN cytotoxicity despite disparate effects on
      adhesion. To assess the role of CD18, beta2-integrin subunits were cross-linked,
      and CD18 alone mediated protease release. Moreover, ICAM-1 was immunoprecipitated
      from transfected CHO cells and incubated with PMNs. This soluble ICAM-1 provoked
      elastase release, similar to PMA, which could be inhibited by MAbs to CD18 but
      not MAbs to other beta2-integrin subunits. In addition, coincubation with
      protease inhibitors eglin C and AAPVCK reduced PMN-mediated cytotoxicity to
      control levels. Finally, ICAM-1-transfected CHO cells were exposed to activated
      PMNs from a patient with chronic granulomatous disease that caused significant
      cell lysis, equivalent to that of PMNs from normal donors. Collectively, these
      data suggest that ICAM-1 provokes PMN-mediated cytotoxicity via CD18-mediated
      protease release.

PMID- 9611131
TI  - Role of cyclic ADP-ribose in the regulation of [Ca2+]i in porcine tracheal smooth
      muscle.
AB  - The purpose of the present study was to determine whether cyclic ADP-ribose
      (cADPR) acts as a second messenger for Ca2+ release through ryanodine receptor
      (RyR) channels in tracheal smooth muscle (TSM). Freshly dissociated porcine TSM
      cells were permeabilized with beta-escin, and real-time confocal microscopy was
      used to examine changes in intracellular Ca2+ concentration ([Ca2+]i). cADPR (10
      nM-10 microM) induced a dose-dependent increase in [Ca2+]i, which was blocked by
      the cADPR receptor antagonist 8-amino-cADPR (20 microM) and by the RyR blockers
      ruthenium red (10 microM) and ryanodine (10 microM), but not by the inositol
      1,4,5-trisphosphate receptor blocker heparin (0.5 mg/ml). During steady-state
      [Ca2+]i oscillations induced by acetylcholine (ACh), addition of 100 nM and 1
      microM cADPR increased oscillation frequency and decreased peak-to-trough
      amplitude. ACh-induced [Ca2+]i oscillations were blocked by 8-amino-cADPR;
      however, 8-amino-cADPR did not block the [Ca2+]i response to a subsequent
      exposure to caffeine. These results indicate that cADPR acts as a second
      messenger for Ca2+ release through RyR channels in TSM cells and may be necessary
      for initiating ACh-induced [Ca2+]i oscillations.

PMID- 9611132
TI  - Developmental regulation of ENaC subunit mRNA levels in rat kidney.
AB  - To assess the role of distal nephron apical Na channel (ENaC) gene expression in
      Na wasting by the immature kidney, ENaC alpha-, beta-, and gamma-subunit mRNA
      levels were examined in the rat by RT-PCR. In microdissected nephron segments,
      all three ENaC subunit mRNAs were detected in the distal convoluted tubule,
      connecting tubule, cortical collecting duct, and outer medullary collecting duct.
      The inner medullary collecting duct and all other nephron segments were
      consistently negative. The mRNA levels were quantified in kidneys at different
      developmental stages by multiplex RT-PCR with "primer dropping," with endoplasmic
      reticulum-specific cyclophilin mRNA as an internal standard. All three ENaC mRNA
      levels were low or undetectable on gestational day 16 and only slightly higher 3
      days before birth. A sharp rise was observed between 3 days before and 1-3 days
      after birth; the levels at postnatal days 1-3 were already similar to those of
      adult kidneys. The results suggest that ENaC subunit gene expression is not a
      limiting factor in the full-term newborn rat kidney, but low levels of expression
      may limit distal Na absorption in more immature kidneys, such as those of very
      premature human infants.

PMID- 9611133
TI  - Beta-adrenergic-induced cytosolic redistribution of Rap1 in rat parotid acini:
      role in secretion.
AB  - Rap1 has recently been identified on the secretory granule membrane and plasma
      membrane of rat parotid acinar cells (N. J. D'Silva, D. DiJulio, C. B. Belton, K.
      L. Jacobson, and E. L. Watson. J. Histochem. Cytochem. 45: 965-973, 1997). In the
      present study, we examined the cellular redistribution of Rap1 following
      treatment of acini with isoproterenol (ISO), the beta-adrenergic agonist, and
      determined the relationship between translocation and amylase release. In the
      presence of ISO, Rap1 translocated to the cytosol in a concentration- and time
      dependent manner; this effect was not mimicked by the muscarinic agonist,
      carbachol. Translocation was maximal at 1 microM ISO and paralleled amylase
      release immediately after ISO stimulation. Rap1 translocation and amylase release
      were blocked by the beta-adrenergic antagonist, propranolol, whereas okadaic
      acid, a downstream secretory inhibitor, significantly blocked amylase release but
      did not inhibit Rap1 redistribution. Results suggest that the translocation of
      Rap1 is causally related to secretion and that the role of Rap1 in secretion is
      at a site proximal to the exocytotic event.

PMID- 9611134
TI  - Expression of adenylyl cyclase mRNAs in the denervated and in the developing
      mouse skeletal muscle.
AB  - Changes in the activity and in the expression of adenylyl cyclase (AC) were
      examined in mouse skeletal muscle after denervation and during development. Four
      isoforms of AC (AC2, AC6, AC7, and AC9) were detected by Northern blot analysis
      in gastrocnemius muscle, AC9 being the most abundant. After denervation, the
      levels of AC2 and AC9 mRNA decreased, whereas those of AC6 and AC7 increased. AC
      activity in response to several neurotransmitters was increased after
      denervation. During development, AC activity was high in fetus and neonate and
      declined in the adult; the sensitivity of AC activity to various
      neurotransmitters was the highest on the third postnatal day. The levels of AC6
      and AC7 mRNAs were high on the third postnatal day and then decreased in adult,
      paralleling the decline in AC activity. All the characteristics of AC expression
      and activity in fetus and neonate resembled those observed in denervated adult
      muscle. These results indicate that changes in AC activity and AC mRNAs play an
      important role in the various physiopathological states of skeletal muscle,
      especially during muscle atrophy.

PMID- 9611135
TI  - Inflammatory cytokines (IL-1alpha, TNF-alpha) and LPS modulate the Ca2+ signaling
      pathway in osteoblasts.
AB  - Locally derived growth factors and cytokines in bone play a crucial role in the
      regulation of bone remodeling, i.e., bone formation and bone resorption
      processes. We studied the effect of interleukin (IL)-1alpha, tumor necrosis
      factor (TNF)-alpha, and Escherichia coli lipopolysaccharide (LPS) on the hormone
      activated Ca2+ message system in the osteoblastic cell line UMR-106 and in
      osteoblastic cultures derived from neonatal rat calvariae. In both cell
      preparations, IL-1alpha, TNF-alpha, and LPS did not alter basal intracellular
      Ca2+ concentration ([Ca2+]i) but attenuated Ca2+ transients evoked by parathyroid
      hormone (PTH) and PGE2 in a dose (1-100 ng/ml)- and time (8-24 h)-dependent
      fashion. The cytokines modulated hormonally induced Ca2+ influx (estimated by
      using Mn2+ as a surrogate for Ca2+) as well as Ca2+ mobilization from
      intracellular stores. The latter was linked to suppressed production of
      hormonally induced inositol 1,4,5-trisphosphate. The effect of cytokines on
      [Ca2+]i was abolished by the tyrosine kinase inhibitor herbimycin A (50 ng/ml).
      The cytokine's effect was, however, independent of nitric oxide (NO) production,
      since NO donors (sodium nitroprusside) as well as permeable cGMP analogs augment,
      rather than attenuate, hormonally induced Ca2+ transients in osteoblasts. Given
      the stimulatory role of cytokines on NO production in osteoblasts, the disparate
      effects of cytokines and NO on the Ca2+ signaling pathway may serve an
      autocrine/paracrine mechanism for modulating the effect of calciotropic hormones
      on bone metabolism.

PMID- 9611136
TI  - Regulation of rENaC mRNA by dietary NaCl and steroids: organ, tissue, and steroid
      heterogeneity.
AB  - Rats on a low-NaCl diet have a high Na+ channel activity in colon and kidney. To
      address the mechanism of this increased activity, we measured mRNA levels of
      three Na+ channel subunits in epithelial tissue (rENaC) from rats having been fed
      either a low (0.13%)- or high (8%)-NaCl diet for 2-3 wk. The size of the mRNA for
      each of the rENaC subunits as determined by Northern blot was unaffected by diet.
      RNase protection assay showed heterogeneity of response by organs and subunit. In
      lung, there was no effect of diet on any of the three subunits. In descending
      colon, the low-NaCl diet increased beta- and gamma-rENaC mRNA, with no effect on
      alpha-rENaC mRNA. In the kidney, the response to dietary NaCl was dependent on
      the region. In cortex and outer medulla, diet had no effect on any of the
      subunits. Rats fed the low-NaCl diet had greater alpha-rENaC in inner medulla but
      not beta- or gamma-rENaC mRNA. We next asked whether acute administration of pure
      glucocorticoid (GC) or mineralocorticoid (MC) hormones to adrenalectomized rats
      reproduced the effects of a low-NaCl diet. Six hours after administration of GC
      or MC, a somewhat different heterogeneity occurred. In lung, alpha-rENaC mRNA was
      increased but only in response to GC. In colon, either GC or MC increased beta-
      or gamma-rENaC, and there was no effect on alpha-rENaC. In kidney, either GC or
      MC increased alpha-rENaC, without an effect on beta- or gamma-rENaC. In contrast
      to the response to a low-NaCl diet, all three regions were similarly affected by
      acute steroids. These results demonstrate a striking heterogeneity in response to
      physiological stimuli that regulate ENaC function. The mRNA levels of each of the
      rENaC subunits can be determined by the type of steroid and by factors unique to
      the organ and even to the specific region of the kidney.

PMID- 9611137
TI  - Occludin is concentrated at tight junctions of mouse/rat but not human/guinea pig
      Sertoli cells in testes.
AB  - Occludin is the only integral membrane protein identified to date as a component
      of tight junctions (TJs). Here, we examined the distribution and expression of
      occludin in murine testis bearing well-developed TJ. In the adult mouse testis,
      occludin was concentrated at TJ strands, which are located at the most basal
      regions of lateral membranes of Sertoli cells. In immunoblotting, occludin showed
      a characteristic multiple banding pattern, suggesting that occludin is highly
      phosphorylated in the testis. In 1-wk-old mouse testis, occludin was distributed
      diffusely at the lateral membranes of Sertoli cells, and even at this stage,
      highly phosphorylated occludin was detected. With development, occludin gradually
      became concentrated at the most basal regions of Sertoli cells. The same results
      were obtained in rat, but unexpectedly occludin was not detected in human or
      guinea pig Sertoli cells by immunofluorescence microscopy as well as by
      immunoblotting. Inasmuch as TJs are also well developed in Sertoli cells of these
      species, we concluded that, at least in the testes of these species, there are
      some Sertoli cell-specific isoforms of occludin or other TJ-associated integral
      membrane proteins that differ from occludin.

PMID- 9611138
TI  - Effect of clenbuterol on sarcoplasmic reticulum function in single skinned
      mammalian skeletal muscle fibers.
AB  - We examined the effect of the beta2-agonist clenbuterol (50 microM) on
      depolarization-induced force responses and sarcoplasmic reticulum (SR) function
      in muscle fibers of the rat (Rattus norvegicus; killed by halothane overdose)
      that had been mechanically skinned, rendering the beta2-agonist pathway
      inoperable. Clenbuterol decreased the peak of depolarization-induced force
      responses in the extensor digitorum longus (EDL) and soleus fibers to 77.2 +/-
      9.0 and 55.6 +/- 5.4%, respectively, of controls. The soleus fibers did not
      recover. Clenbuterol significantly and reversibly reduced SR Ca2+ loading in EDL
      and soleus fibers to 81.5 +/- 2.8 and 78.7 +/- 4.0%, respectively, of controls.
      Clenbuterol also produced an approximately 25% increase in passive leak of Ca2+
      from the SR of the EDL and soleus fibers. These results indicate that clenbuterol
      has direct effects on fast- and slow-twitch skeletal muscle, in the absence of
      the beta2-agonist pathway. The increased Ca2+ leak in the triad region may lead
      to excitation-contraction coupling damage in the soleus fibers and could also
      contribute to the anabolic effect of clenbuterol in vivo.

PMID- 9611139
TI  - Selective hydrolysis of plasmalogen phospholipids by Ca2+-independent PLA2 in
      hypoxic ventricular myocytes.
AB  - Accelerated phospholipid catabolism occurs early after the onset of myocardial
      ischemia and is likely to be mediated by the activation of one or more
      phospholipases in ischemic tissue. We hypothesized that hypoxia increases
      phospholipase A2 (PLA2) activity in isolated ventricular myocytes, resulting in
      increased lysophospholipid and arachidonic acid production, contributing to
      arrhythmogenesis in ischemic heart disease. The majority of ventricular myocyte
      arachidonic acid was found in plasmalogen phospholipids. Hypoxia increased
      membrane-associated, Ca2+-independent, plasmalogen-selective PLA2 activity,
      resulting in increased arachidonic acid release and lysoplasmenylcholine
      production. Pretreatment with the specific Ca2+-independent PLA2 inhibitor
      bromoenol lactone blocked hypoxia-induced increases in PLA2 activity, arachidonic
      acid release, and lysoplasmenylcholine production. Lysoplasmenylcholine produced
      action potential derangements, including shortening of action potential duration,
      and induced early and delayed afterdepolarizations in normoxic myocytes. The
      electrophysiological alterations induced by lysoplasmenylcholine would likely
      contribute to the initiation of arrhythmogenesis in the ischemic heart.

PMID- 9611140
TI  - Control of heat production by the Ca2+-ATPase of rabbit and trout sarcoplasmic
      reticulum.
AB  - The sarcoplasmic reticulum Ca2+-ATPase of rabbit skeletal muscle can convert the
      energy derived from a Ca2+ gradient into heat (L. de Meis, M. L. Bianconi, and V.
      A. Suzano. FEBS Lett. 406: 201-204, 1997). In this report, it is shown that this
      conversion varies depending on the temperature and on whether rabbit (endotherm)
      or trout (poikilotherm) sarcoplasmic reticulum vesicles are used. The gradient
      doubled the yield of heat produced during ATP hydrolysis and the calorimetric
      enthalpy of ATP hydrolysis (DeltaHcal) value found with both rabbit and trout
      varied between -10 and -12 kcal/mol in leaky vesicles (no gradient) and between 
      20 and -22 kcal/mol with intact vesicles (gradient). For the rabbit, the
      difference of DeltaHcal measured with and without gradient was detected in the
      range of 30-35 degrees C and disappeared when the temperature was decreased below
      30 degrees C. For the trout, the difference was detected between 20 and 25
      degrees C and disappeared below 20 degrees C. The effect of the gradient on the
      DeltaHcal for ATP hydrolysis was modified by DMSO, trifluoperazine, and heparin
      sodium.

PMID- 9611141
TI  - Synergism between toxin-gamma from Brazilian scorpion Tityus serrulatus and
      veratridine in chromaffin cells.
AB  - Toxin-gamma (Tgamma) from the Brazilian scorpion Tityus serrulatus venom caused a
      concentration- and time-dependent increase in the release of norepinephrine and
      epinephrine from bovine adrenal medullary chromaffin cells. Tgamma was
      approximately 200-fold more potent than veratridine judged from EC50 values,
      although the maximal secretory efficacy of veratridine was 10-fold greater than
      that of Tgamma (1.2 vs. 12 microg/ml of catecholamine release). The combination
      of both toxins produced a synergistic effect that was particularly drastic at 5
      mM extracellular Ca2+ concentration ([Ca2+]o), when 30 microM veratridine plus
      0.45 microM Tgamma were used. Tgamma (0.45 microM) doubled the basal uptake of
      45Ca2+, whereas veratridine (100 microM) tripled it. Again, a drastic synergism
      in enhancing Ca2+ entry was seen when Tgamma and veratridine were combined; this
      was particularly pronounced at 5 mM [Ca2+]o. Veratridine induced oscillations of
      cytosolic Ca2+ concentration ([Ca2+]i) in single fura 2-loaded cells without
      elevation of basal levels. In contrast, Tgamma elevated basal [Ca2+]i levels,
      causing only small oscillations. When added together, Tgamma and veratridine
      elevated the basal levels of [Ca2+]i without causing large oscillations. Tgamma
      shifted the current-voltage (I-V) curve for Na+ channel current to the left. The
      combination of Tgamma with veratridine increased the shift of the I-V curve to
      the left, resulting in a greater recruitment of Na+ channels at more
      hyperpolarizing potentials. This led to enhanced and more rapid accumulation of
      Na+ in the cell, causing cell depolarization, the opening of voltage-dependent
      Ca2+ channels, and Ca2+ entry and secretion.

PMID- 9611142
TI  - Voltage dependence of Ca2+ sparks in intact cerebral arteries.
AB  - Ca2+ sparks have been previously described in isolated smooth muscle cells. Here
      we present the first measurements of local Ca2+ transients ("Ca2+ sparks") in an
      intact smooth muscle preparation. Ca2+ sparks appear to result from the opening
      of ryanodine-sensitive Ca2+ release (RyR) channels in the sarcoplasmic reticulum
      (SR). Intracellular Ca2+ concentration ([Ca2+]i) was measured in intact cerebral
      arteries (40-150 micron in diameter) from rats, using the fluorescent Ca2+
      indicator fluo 3 and a laser scanning confocal microscope. Membrane potential
      depolarization by elevation of external K+ from 6 to 30 mM increased Ca2+ spark
      frequency (4. 3-fold) and amplitude (approximately 2-fold) as well as global
      arterial wall [Ca2+]i (approximately 1.7-fold). The half time of decay (
      approximately 50 ms) was not affected by membrane potential depolarization.
      Ryanodine (10 microM), which inhibits RyR channels and Ca2+ sparks in isolated
      cells, and thapsigargin (100 nM), which indirectly inhibits RyR channels by
      blocking the SR Ca2+-ATPase, completely inhibited Ca2+ sparks in intact cerebral
      arteries. Diltiazem, an inhibitor of voltage-dependent Ca2+ channels, lowered
      global [Ca2+]i and Ca2+ spark frequency and amplitude in intact cerebral arteries
      in a concentration-dependent manner. The frequency of Ca2+ sparks (<1 s-1 . cell
      1), even under conditions of steady depolarization, was too low to contribute
      significant amounts of Ca2+ to global Ca2+ in intact arteries. These results
      provide direct evidence that Ca2+ sparks exist in quiescent smooth muscle cells
      in intact arteries and that changes of membrane potential that would simulate
      physiological changes modulate both Ca2+ spark frequency and amplitude in
      arterial smooth muscle.

PMID- 9611143
TI  - Acetogenesis does not replace ketogenesis in fasting piglets infused with
      hexanoate.
AB  - The current studies were performed to better understand the physiological
      relevance of acetate in the poorly ketogenic piglet and to determine if
      endogenous acetogenesis rises with increased mitochondrial fatty acid beta
      oxidation, analogous to ketogenesis. Plasma acetate concentration values in
      newborn, fasted, or suckled piglets (230-343 microM) were at least 10-fold higher
      than the ketone bodies, a pattern opposite to that in 24- to 48-h suckled rats
      (77-175 microM). Employing continuous infusion techniques with sodium [3H]acetate
      tracer in fasting approximately 40-h-old piglets, acetate rate of appearance (Ra)
      was found to be 34 +/- 4 micromol . min-1 . kg body wt-1. This basal Ra was
      double that observed in animals coinfused with sodium [1-14C]hexanoate (P <
      0.001), despite active oxidation of the latter as determined by 14CO2 production.
      Active acetogenesis in vivo and relatively abundant acetate in piglet blood are
      consistent with the hypothesis that acetate plays an important physiological role
      in piglets. However, the negative impact of hexanoate oxidation upon acetate Ra
      and the lack of significant changes in circulating acetate in newborn, suckled,
      and fasted piglets draws into question the extent of analogy between acetogenesis
      and ketogenesis in vivo.

PMID- 9611144
TI  - alpha-MSH potentiates the responsiveness of mammotropes by increasing Ca2+ entry.
AB  - It is well known that the suckling stimulus renders mammotropes considerably more
      responsive to prolactin (PRL)-releasing stimuli, and the neurointermediate lobe
      peptide alpha-melanocyte-stimulating hormone (alpha-MSH) has been proposed to
      play a pivotal role in this priming. The objectives of the present study were to
      determine whether alpha-MSH could act directly on pituitary cells to potentiate
      PRL release in response to two physiologically relevant PRL secretagogues,
      thyrotropin-releasing hormone (TRH) and ATP, and, if so, to identify the
      mechanism by which this priming phenomenon is manifested. To this end, we
      cultured anterior pituitary cells from lactating rats overnight and then
      subjected them to a reverse hemolytic plaque assay for PRL to evaluate their
      responses to various test agents. We found that alpha-MSH, which had no effect on
      PRL export when tested alone, augmented by more than threefold the secretory
      responses to TRH and ATP. Next, we utilized digital-imaging fluorescence
      microscopy of fura 2 to evaluate the role of intracellular Ca2+ in this process.
      We found that PRL export induced by pharmacological activation of L-type voltage
      operated calcium channels was also potentiated by alpha-MSH, as was Ca2+ entry
      induced by TRH. Our results indicate that alpha-MSH acts as a mammotrope-priming
      agent on a subset of mammotropes by increasing Ca2+ entry induced by PRL
      secretagogues.

PMID- 9611145
TI  - Regional acetate kinetics and oxidation in human volunteers.
AB  - We have used a 3-h primed continuous infusion of [1,2-13C]acetate in five fasted
      (24 h) volunteers to quantify splanchnic and leg acetate metabolism (protocol 1).
      Fractional extraction of acetate by both tissues was high ( approximately 70%),
      and simultaneous uptake and release of acetate were observed. Labeled carbon
      recovery in CO2 was 37.9 +/- 2.3% at the whole body level, 37.7 +/- 1.5% across
      the splanchnic bed, and 37.3 +/- 2.9% across the leg. Furthermore, we calculated
      whole body labeled carbon recovery during 15 h of [1, 2-13C]acetate infusion in
      three volunteers (protocol 2). Whole body acetate carbon recovery in CO2 was
      significantly higher (66.7 +/- 4. 5%) after 15 h of tracer infusion than after 3
      h. We conclude that acetate is rapidly taken up by the leg and splanchnic tissues
      and that the percent recovery of CO2 from the oxidation of acetate is heavily
      dependent on the length of acetate tracer infusion. In the postabsorptive state,
      labeled carbon recovery from acetate across the leg and the splanchnic region is
      similar to the whole body CO2 recovery.

PMID- 9611147
TI  - Endotoxin-induced alteration in the expression of leptin and beta3-adrenergic
      receptor in adipose tissue.
AB  - Cytokines, such as tumor necrosis factor (TNF) and interleukin-6, may contribute
      to the anorexia and cachexia of infection, cancer, and AIDS. The present study
      tests the hypothesis that endotoxin alters the expression of two key fat cell
      proteins, leptin and beta3-adrenergic receptor (beta3-AR), through a mechanism
      involving TNF-alpha. Increasing doses of Escherichia coli endotoxin
      (lipopolysaccharide, LPS) resulted in dose-dependent elevations of plasma leptin
      (maximal response approximately 7-fold, half-maximal effective dose of
      approximately 16 microg/100 g body wt) and white fat leptin mRNA in C3/HeOUJ
      mice. LPS also produced a large decrease in adipose tissue beta3-AR mRNA and a
      parallel reduction in beta-agonist-induced activation of adenylyl cyclase.
      Changes in plasma leptin and beta3-AR mRNA were preceded by an approximately
      threefold increase in white fat TNF mRNA. TNF administration resulted in changes
      similar to those seen with LPS. We conclude that endotoxemia results in an
      induction of leptin mRNA and a decrease in beta3-AR mRNA in adipose tissue, an
      effect that may be mediated by alterations in TNF-alpha.

PMID- 9611146
TI  - Glycemia-lowering effect of cobalt chloride in the diabetic rat: role of
      decreased gluconeogenesis.
AB  - Results of previous studies indicated that treatment of diabetic rats (induced by
      streptozotocin) with cobalt chloride (CoCl2) resulted in a significant decrement
      in serum glucose concentration. The present study was designed to determine the
      potential role of enhanced glucose uptake vs. decreased glucose production in the
      above response. The rate of systemic appearance of glucose, measured under
      fasting conditions using [3-3H]glucose tracer, was reduced from 35.5 +/- 2.5 to
      17.5 +/- 1.8 micromol . kg-1 . min-1 in diabetic rats treated with 2 mM CoCl2
      added to the drinking water for 10-14 days (P < 0.01). Tissue accumulation of
      intravenously administered 2-deoxy-[14C]glucose was significantly reduced in
      kidney and eye of diabetic rats treated with CoCl2, whereas the uptake remained
      unchanged in several other tissues including cerebrum, red and white skeletal
      muscle, heart, and liver. The relative content of phosphoenolpyruvate
      carboxykinase (PEPCK) mRNA was increased 3.1-fold in livers of diabetic compared
      with normal rats (P < 0.001), and treatment of diabetic rats with CoCl2 decreased
      hepatic PEPCK mRNA levels to normal. The content of PEPCK mRNA in the liver was
      decreased by 33% in CoCl2-treated normal rats (P < 0.05). Treatment with CoCl2
      resulted in no change in cAMP levels in the livers of either diabetic or normal
      rats. These results suggest that the glycemia-lowering effect of CoCl2 is
      mediated by reductions in the rate of systemic appearance of glucose and hepatic
      gluconeogenesis.

PMID- 9611148
TI  - Effect of hyperinsulinemia on plasma leptin concentrations and food intake in
      rats.
AB  - We investigated the dose- and time-dependent effect of insulin infusion on
      peripheral and portal plasma leptin concentrations in normal rats. Three groups
      were studied: group I: euglycemic (6 mmol/l) insulin (6 mU . kg-1 . min-1) clamps
      for 0, 2, 4, 12, and 24 h; group II: euglycemic insulin (18 mU . kg-1 . min-1)
      clamp for 2 h; and group III: euglycemic insulin (3 mU . kg-1 . min-1) clamp for
      7 days. In group III, food intake was quantified during days 1-7. After an
      overnight fast, peripheral and portal plasma leptin levels were identical (1.5 +/
      0.2 and 1.6 +/- 0.2 ng/ml). Insulin infusion (6 mU . kg-1 . min-1) for 2 h had
      no effect on plasma leptin levels (1.5 +/- 0.2 ng/ml). After 4 h (2.0 +/- 0.2
      ng/ml), 12 h (2.2 +/- 0. 4 ng/ml), and 24 h (2.7 +/- 0.6 ng/ml; all P < 0.05) of
      insulin infusion, a progressive time-related increase in plasma leptin
      concentration was observed; portal vein leptin levels rose in parallel and were
      similar to peripheral levels. When insulin (18 mU . kg-1 . min-1) was infused for
      2 h, plasma leptin levels increased to 3.0 +/- 0.3 ng/ml (P < 0.01). Seven days
      of constant insulin infusion (3 mU . kg-1 . min-1) resulted in a progressive
      increase in fasting plasma leptin and a parallel decrease in food intake. A mean
      increase in plasma leptin concentration of 1 ng/ml during the 7-day insulin
      infusion period was associated with a mean decrease in food intake of 2.5 g/day
      (multivariate ANOVA, P < 0.05). We conclude that the insulin-induced rise in
      peripheral and portal vein leptin levels is similar and both dose and time
      dependent. The inverse relationship between plasma leptin concentration and food
      intake during prolonged hyperinsulinemia, but not during short-term
      hyperinsulinemia, supports the role of leptin in long-term food consumption.

PMID- 9611149
TI  - Mechanisms involved in the protective effect of estradiol-17beta on lipid
      peroxidation and DNA damage.
AB  - Previous studies from our laboratory have shown that estrogens can protect
      against lipoprotein peroxidation and DNA damage. In this study, the mechanism of
      estradiol-17beta (E2) action was investigated by comparing E2 with selective
      scavengers of reactive oxygen species (ROS) in terms of inhibition of 1) human
      low-density lipoprotein (LDL) peroxidation (measured by the diene conjugation
      method) and 2) DNA damage (measured by the formation of strand breaks in
      supercoiled OX-174 RFI DNA). In addition, the direct effect of E2 on the
      generation of individual ROS was also measured. By use of ROS scavengers, it was
      determined that lipoprotein peroxidation was predominantly due to superoxide
      (39%), with some contributions from hydrogen peroxide (23%) and peroxy (38%)
      radicals. E2 was a more effective inhibitor of peroxidation than all the ROS
      scavengers combined. In DNA damage, scavengers of hydrogen peroxide, hydroxyl,
      and superoxide radical offered significant protection (49-65%). E2 alone offered
      a similar degree of protection, and no additional effect was evident when it was
      combined with ROS scavengers. E2 caused a significant reduction (37%) in the
      production of superoxide radical by bovine heart endothelial cells in culture but
      had no effect on the formation of either hydrogen peroxide or hydroxyl radicals.
      These studies show that 1) the protection offered by E2 in terms of lipid
      peroxidation could be due to its ability to inhibit generation of superoxide
      radical and prevent further chain propagation, and 2) in DNA damage protection,
      E2 mainly appears to inhibit chain propagation.

PMID- 9611151
TI  - Thyroid receptor plasticity in striated muscle types: effects of altered thyroid
      state.
AB  - This study examined nuclear thyroid receptor (TR) maximum binding capacity
      (Bmax), dissociation constant (Kd), and TR isoform (alpha1, alpha2, beta1) mRNA
      expression in rodent cardiac, "fast-twitch white," "fast-twitch red," and "slow
      twitch red" muscle types as a function of thyroid state. These analyses were
      performed in the context of slow-twitch type I myosin heavy-chain (MHC)
      expression, a 3,5,3'-triiodothyronine (T3)-regulated gene that displays varying
      responsiveness to T3 in the above tissues. Nuclear T3 binding analyses show that
      the skeletal muscle types express more TRs per unit DNA than cardiac muscle,
      whereas the latter has a lower Kd than the former. Altered thyroid state had
      little effect on either cardiac Bmax or Kd, whereas hypothyroidism increased Bmax
      in the skeletal muscle types without affecting its Kd. Cardiac muscle
      demonstrated the greatest mRNA signal of TR-beta1 compared with the other muscle
      types, whereas the TR-alpha1 mRNA signals were more abundant in the skeletal
      muscle types, especially fast-twitch red. Hyperthyroidism increased the ratio of
      beta1 to alpha1 and decreased the ratio of alpha2- to alpha1+beta1-mRNA signal
      across the muscle types, whereas hypothyroidism caused the opposite effects. The
      nuclear T3 affinity correlated significantly with the TR-beta1 mRNA expression
      but not with TR-alpha1 mRNA expression. Collectively, these findings suggest
      that, despite a divergent pattern of TR mRNA expression in the different muscle
      types, these patterns follow similar qualitative changes under altered thyroid
      state. Furthermore, TR expression pattern cannot account for the quantitative and
      qualitative changes in type I MHC expression that occur in the different muscle
      types.

PMID- 9611150
TI  - Adiposity and serum leptin increase in fatty (fa/fa) BNZ neonates without
      decreased VMH serotonergic activity.
AB  - Decreased ventromedial hypothalamic (VMH) serotonergic activity occurs in genetic
      and diet-induced animal models of obesity. We previously found that this activity
      was lower in adult and in 12-day-old Zucker fa/fa vs. Fa/Fa pups, the fa/fa
      animals being identified by their greater adiposity. In the present study, we
      evaluated fa/fa rats (Brown Norway-Zucker hybrids) at ages 2, 4, 7, and 12 days
      to test the hypothesis that lower VMH serotonergic activity occurs before
      increased adiposity and/or attenuated energy expenditure. Our results negate this
      hypothesis. VMH serotonergic activity showed no consistent genotype differences
      even at 12 days of age. In contrast, by day 7, fa/fa vs. Fa/Fa pups had higher
      serum leptin concentrations, greater percent body fat, lower resting and cold
      induced energy expenditure, and lower activity of brown fat thyroxine 5'
      deiodinase, an enzyme that converts thyroxine to triiodothyronine. We conclude
      that the onset of increased adiposity induced by the fa gene does not require
      decreased VMH serotonergic activity and that the lower serotonergic activity seen
      in older fa/fa pups may be secondary to metabolic consequences of the disruption
      of the leptin regulatory pathway.

PMID- 9611152
TI  - Fat balance in obese subjects: role of glycogen stores.
AB  - In a previous study, we showed that lean subjects are capable of rapidly
      adjusting fat oxidation to fat intake on a high-fat (HF) diet when glycogen
      stores are lowered by exhaustive exercise. However, it has been proposed that
      obese subjects have impaired fat oxidation. We therefore studied the effect of
      low glycogen stores on fat oxidation after a switch from a reduced-fat (RF) diet
      to an HF diet in obese subjects. Ten healthy, obese male and female subjects (26
      +/- 2 yr, body mass index 31.8 +/- 1.4, maximal power output 228 +/- 14 W)
      consumed an RF diet (30, 55, and 15% of energy from fat, carbohydrate, and
      protein, respectively) at home for 3 days on four occasions (days 1-3). On two
      occasions, subjects came to the laboratory on day 3 at 1500 to perform an
      exhaustive glycogen-lowering exercise test (Ex), after which they went into a
      respiration chamber for a 36-h stay. On the other two occasions, subjects
      directly entered the respiration chamber at 1800 for a 36-h stay. In the
      respiration chamber, they were fed, in energy balance, either an HF diet (60, 25,
      and 15% of energy from fat, carbohydrate, and protein, respectively) or an RF
      diet. All diets were consumed as breakfast, lunch, dinner, and two or more snacks
      per day. Twenty-four-hour respiratory quotient was 0.91 +/- 0.01, 0.89 +/- 0.01,
      0.84 +/- 0.01, and 0.81 +/- 0.01 with RF diet, RF + Ex, HF, and HF + Ex
      treatments, respectively. With the HF treatment, fat oxidation was below fat
      intake, indicating the slow change of oxidation to intake on an HF diet. After
      the HF + Ex treatment, however, fat oxidation matched fat intake. In conclusion,
      obese subjects are capable of rapidly adjusting fat oxidation to fat intake when
      glycogen stores are lowered by exhaustive exercise.

PMID- 9611153
TI  - Vagotomy in young obese hyperglycemic mice: effects on syndrome development and
      islet proliferation.
AB  - Obese hyperglycemic mice have large pancreatic islets and high levels of serum
      insulin and blood glucose. Vagotomy was performed on 3-wk-old animals to
      investigate the role of gut cholinergic innervation in young Umea ob/ob mice.
      After vagotomy, obesity and hyperglycemia are dissociated. Weight increase in
      obese vagotomized mice was lower than in sham-operated controls during the 1st wk
      postoperatively but not thereafter. Blood glucose was lower up to 5 mo after
      vagotomy, but vagotomized mice showed reduced glucose tolerance. Islet cell
      proliferation rate was reduced 2 and 3 wk but not 5 mo after vagotomy. After 5
      mo, islet volume was smaller in vagotomized mice. Serum insulin levels were the
      same in vagotomized animals as in sham-operated controls. The effects of reduced
      cholinergic innervation are probably caused both by direct effects of denervation
      and by lowered metabolic demand.

PMID- 9611154
TI  - Effects of exercise on neuroendocrine secretions and glucose regulation at
      different times of day.
AB  - To study the effects of time of day on neuroendocrine and metabolic responses to
      exercise, body temperature, plasma glucose, insulin secretion rates (ISR), and
      plasma cortisol, growth hormone (GH) and thyrotropin (TSH) were measured in young
      men, both at bed rest and during a 3-h exercise period (40-60% maximal O2
      uptake). Exercise was performed at three times of day characterized by marked
      differences in cortisol levels, i.e., early morning (n = 5), afternoon (n = 8),
      and around midnight (n = 9). The subjects were kept awake and fasted, but they
      received a constant glucose infusion to avoid hypoglycemia. Exercise-induced
      elevations of temperature were higher in the early morning than at other times of
      day. The exercise-induced glucose decrease was approximately 50% greater around
      midnight, when cortisol was minimal and not stimulated by exercise, than in the
      afternoon or early morning (P < 0.05). This effect of time of day appeared
      unrelated to decreases in ISR or increases in temperature and GH. Robust TSH
      increases occurred in all exercise periods and were maximal at night. The results
      demonstrate the existence of circadian variations in neuroendocrine and metabolic
      responses to exercise.

PMID- 9611155
TI  - Effect of growth hormone treatment on postprandial protein metabolism in growth
      hormone-deficient adults.
AB  - Growth hormone (GH) treatment of GH-deficient adults increases lean body mass. To
      investigate this anabolic effect of GH, body composition and postabsorptive and
      postprandial protein metabolism were measured in 12 GH-deficient adults
      randomized to placebo or GH treatment. Protein metabolism was measured after an
      infusion of [1-13C]leucine before and after a standard meal at 0 and 2 mo. After
      2 mo, there was an increase in lean body mass in the GH group (P < 0. 05) but no
      change in the placebo group. In the postabsorptive state, there was increased
      nonoxidative leucine disappearance (NOLD; a measure of protein synthesis) and
      leucine metabolic clearance rate and decreased leucine oxidation in the GH group
      (P < 0.05) but no change in the placebo group. After the meal, there was an
      increase in NOLD and oxidation in all studies (P < 0.05), but the increase in
      NOLD, measured as area under the curve, was greater in the GH group (P < 0.05).
      This study clearly demonstrates for the first time that the increase in protein
      synthesis in the postabsorptive state after GH treatment of GH-deficient adults
      is maintained in the postprandial state.

PMID- 9611156
TI  - Behavioral and endocrine traits of obesity-prone and obesity-resistant rats on
      macronutrient diets.
AB  - Patterns of eating behavior, body weight gain, and hormone changes were examined
      in normal-weight albino Sprague-Dawley rats on macronutrient diets. These diets
      consisted of either three separate jars with pure macronutrients, fat,
      carbohydrate and protein, from which to choose, or a single diet with different
      concentrations of fat and carbohydrate. Similar patterns on the choice-diet and
      single-diet paradigms were observed. During the first 7-10 days on these diets
      but not subsequently, the rats consuming a fat-rich diet exhibit significant
      hyperphagia, an increase in both total and fat intake that produces higher body
      weight gain. Compared with a 10% fat diet, a 30% fat diet is associated with a
      decline in insulin and corticosterone (CORT) levels, whereas a 60% fat diet
      produces an increase in circulating glucose. Levels of glucose are positively
      correlated with fat intake, and together these measures are consistently related
      to body fat. These relationships are most strongly expressed in rats that consume
      a fat-rich diet with >30% fat. Whereas insulin levels are also positively related
      to body fat, CORT is inversely related in these normal-weight subjects. In
      animals consuming a high-fat diet, a clear separation can be seen between
      "obesity-prone" (OP) rats with 100% greater body fat than "obesity-resistant"
      (OR) rats. The OP rats, which consume 15% more total calories, have significantly
      higher insulin and glucose levels. In animals that consume a diet with >30% fat,
      it is the OP but not the OR rats that exhibit a positive relation between fat
      intake, glucose levels, and body fat and reveal an additional association between
      carbohydrate intake, insulin, and body fat. Thus these rats on macronutrient
      diets exhibit distinct traits that relate behavior to hormone disturbances and
      adiposity and distinguish subjects that are prone vs. resistant to obesity.

PMID- 9611157
TI  - Extreme hyperinsulinemia unmasks insulin's effect to stimulate protein synthesis
      in the human forearm.
AB  - Insulin clearly stimulates skeletal muscle protein synthesis in vitro.
      Surprisingly, this effect has been difficult to reproduce in vivo. As in vitro
      studies have typically used much higher insulin concentrations than in vivo
      studies, we examined whether these concentration differences could explain the
      discrepancy between in vitro and in vivo observations. In 14 healthy volunteers,
      we raised forearm insulin concentrations 1,000-fold above basal levels while
      maintaining euglycemia for 4 h. Amino acids (AA) were given to either maintain
      basal arterial (n = 4) or venous plasma (n = 6) AA or increment arterial plasma
      AA by 100% (n = 4) in the forearm. We measured forearm muscle glucose, lactate,
      oxygen, phenylalanine balance, and [3H]phenylalanine kinetics at baseline and at
      4 h of insulin infusion. Extreme hyperinsulinemia strongly reversed
      postabsorptive muscle's phenylalanine balance from a net release to an uptake (P
      < 0.001). This marked anabolic effect resulted from a dramatic stimulation of
      protein synthesis (P < 0.01) and a modest decline in protein degradation.
      Furthermore, this effect was seen even when basal arterial or venous
      aminoacidemia was maintained. With marked hyperinsulinemia, protein synthesis
      increased further when plasma AA concentrations were also increased (P < 0.05).
      Forearm blood flow rose at least twofold with the combined insulin and AA
      infusion (P < 0.01), and this was consistent in all groups. These results
      demonstrate an effect of high concentrations of insulin to markedly stimulate
      muscle protein synthesis in vivo in adults, even when AA concentrations are not
      increased. This is similar to prior in vitro reports but distinct from
      physiological hyperinsulinemia in vivo where stimulation of protein synthesis
      does not occur. Therefore, the current findings suggest that the differences in
      insulin concentrations used in prior studies may largely explain the previously
      reported discrepancy between insulin action on protein synthesis in adult muscle
      in vivo vs. in vitro.

PMID- 9611158
TI  - Effect of aging on beta-adrenergically mediated thermogenesis in men.
AB  - The age-dependent alterations in beta-adrenergically mediated thermogenesis were
      investigated in 11 young (mean +/- SE age: 21.9 +/- 0.5 yr) and 9 older (52.9 +/-
      2.1 yr) men during intravenous infusion of the nonselective beta-agonist
      isoprenaline (Iso). The older men had higher basal plasma norepinephrine (327.7
      +/- 35.8 vs. 159.0 +/- 18.2 pg/ml, P < 0.001) and epinephrine (75.1 +/- 18.1 vs.
      29.1 +/- 5.3 pg/ml, P < 0.05) concentrations than the young. The beta
      adrenergically mediated thermogenesis was diminished in the older men, as
      reflected by the significantly higher plasma Iso concentration needed to increase
      resting energy expenditure by 15% (236.1 +/- 51.0 vs. 107.6 +/- 11.4 pg/ml, P <
      0.05). Additionally, both dose (39.4 +/- 6.6 vs. 19.1 +/- 1.5 ng . kg fat-free
      mass-1 . min-1, P < 0.01) and plasma concentration (332.2 +/- 59.1 vs. 119.3 +/-
      14.0 pg/ml, P < 0.01) of Iso needed to increase resting heart rate by 25
      beats/min were higher in older than in younger subjects, suggesting that the age
      related decline in beta-adrenergic sensitivity is a generalized defect not
      related to a specific tissue or response. In conclusion, aging is associated with
      a diminished beta-adrenergically mediated thermogenesis. This blunted thermogenic
      response may contribute to a positive energy balance and thus promote increased
      fat storage and obesity.

PMID- 9611159
TI  - Skeletal muscle malonyl-CoA content at the onset of exercise at varying power
      outputs in humans.
AB  - To investigate the regulation of intramuscular fuel selection, we measured the
      malonyl-CoA (M-CoA) content in human skeletal muscle at three exercise power
      outputs [35, 65, and 90% maximal rate of O2 consumption (VO2 max)]. Four males
      and four females cycled for 10 min at one power output on three separate
      occasions with muscle biopsies sampled at rest and at 1 and 10 min. The
      respiratory exchange ratio was 0.84 +/- 0.03, 0.92 +/- 0.02, and >1.0 at 35, 65
      and 90% VO2 max, respectively. Muscle lactate content increased and
      phosphocreatine content decreased as a function of power output. Pyruvate
      dehydrogenase a activity increased from 0.40-0.64 mmol . kg wet muscle-1 . min-1
      at rest to 1.57 +/- 0.28, 2.80 +/- 0.41, and 3. 28 +/- 0.27 mmol . kg wet muscle
      1 . min-1 after 1 min of cycling at the three power outputs, respectively. Mean
      resting M-CoA contents were similar at all power outputs (1.85-1.98 micromol/kg
      dry muscle). During exercise at 35% VO2 max, M-CoA decreased from rest at 1 min
      (1.85 +/- 0.29 to 1.20 +/- 0.12 micromol/kg dry muscle) but returned to rest
      level by 10 min (1.86 +/- 0.25 micromol/kg dry muscle). M-CoA content did not
      decrease during cycling at 65% VO2 max. At 90% VO2 max, M-CoA did not increase
      despite significant acetyl-CoA accumulation (the substrate for M-CoA synthesis).
      The data suggest that a decrease in M-CoA content is not required for the
      increase in free fatty acid uptake and oxidation that occurs during exercise at
      35 and 65% VO2 max. Furthermore, M-CoA content does not increase during exercise
      at 90% VO2 max and does not contribute to the lower rate of fat oxidation at this
      power output.

PMID- 9611160
TI  - Genetic variability in melatonin concentrations in ewes originates in its
      synthesis, not in its catabolism.
AB  - We investigated whether the genetic difference in plasma melatonin concentration
      in ewes was due to differences in the synthesis pathway from the pineal gland or
      in the catabolism of the hormone. Two groups of ewes [9 low (L) and 10 high (H)]
      were selected according to the breeding value of their mean nighttime plasma
      melatonin concentrations estimated at winter and summer solstices. In response to
      an identical dose of melatonin administered intravenously at 9:00 AM, no
      differences between groups were observed for any of the kinetic parameters:
      clearance rate, steady-state volume of distribution, terminal half-lives, and
      mean residence times. In the second experiment, two series of frequent blood
      samples were performed, one in the middle of the dark phase with samples taken
      every 5 min, and the other over 24 h with hourly samples. Highly significant
      differences between groups in nocturnal melatonin production rate were observed
      (L: 25.7 +/- 2.8 vs. H: 63.1 +/- 8.9 microg . kg-1 . h-1, P < 0.01). Thus the
      genetic differences in plasma melatonin concentrations in ewes originate in the
      synthesis pathway of the melatonin from the pineal gland rather than from
      differences in the catabolism of the hormone.

PMID- 9611161
TI  - Remodeling of the HDL in NIDDM: a fundamental role for cholesteryl ester transfer
      protein.
AB  - When the Ay gene is expressed in KK mice, the yellow offspring (KKAy mice) become
      obese, insulin resistant, hyperglycemic, and severely hypertriglyceridemic, yet
      they maintain extraordinarily high plasma high-density lipoprotein (HDL) levels.
      Mice lack the ability to redistribute neutral lipids among circulating
      lipoproteins, a process catalyzed in humans by cholesteryl ester transfer protein
      (CETP). To test the hypothesis that it is the absence of CETP that allows these
      hypertriglyceridemic mice to maintain high plasma HDL levels, simian CETP was
      expressed in the KKAy mouse. The KKAy-CETP mice retained the principal
      characteristics of KKAy mice except that their plasma HDL levels were reduced
      (from 159 +/- 25 to 25 +/- 6 mg/dl) and their free apolipoprotein A-I
      concentrations increased (from 7 +/- 3 to 22 +/- 6 mg/dl). These changes appeared
      to result from a CETP-induced enrichment of the HDL with triglyceride (from 6 +/-
      2 to 60 +/- 18 mol of triglyceride/mol of HDL), an alteration that renders HDL
      susceptible to destruction by lipases. These data support the premise that CETP
      mediated remodeling of the HDL is responsible for the low levels of that
      lipoprotein that accompany hypertriglyceridemic non-insulin-dependent diabetes
      mellitus.

PMID- 9611162
TI  - Preferential utilization of newly synthesized cholesterol for brain growth in
      neonatal lambs.
AB  - These studies used the suckling lamb as a model to determine the sources of
      cholesterol that are utilized for development of the central nervous system in
      the neonate. Lambs were studied at 1.3 and 16.4 days after birth. Over this 15
      day interval, 14 g of new brain tissue were formed. About 9-10 mg of cholesterol
      were utilized daily for this new tissue growth. To determine the source of this
      cholesterol, the absolute rates of low-density lipoprotein clearance and
      cholesterol synthesis were measured in vivo in nine separate regions of the
      central nervous system. Low-density lipoprotein clearance throughout the brain
      was very low and at most could have contributed only 0.3-0.4 mg cholesterol daily
      for new brain growth. In contrast, the brain synthesized 7-8 mg of
      cholesterol/day. There were pronounced regional differences in the concentration
      of cholesterol throughout the brain, and these correlated closely with the rate
      of sterol synthesis (r = 0.95) in these same regions. We conclude that the
      principal source of sterol for brain growth in suckling lambs is de novo
      synthesis.

PMID- 9611163
TI  - Beta-adrenergic receptor number in human lymphocytes is inversely correlated with
      aerobic capacity.
AB  - In the present study, the relationships between beta-adrenergic receptor (beta
      AR) expression and aerobic capacity evaluated by maximal oxygen consumption
      (.VO2max) and oxygen consumption level at ventilatory threshold (.VO2@VT) were
      investigated. Seventeen physically untrained and 25 trained men participated in
      the study. After supine resting, the peripheral blood was sampled for preparation
      of lymphocytes, the model cell used to analyze the beta-AR state. The total
      number of beta-AR in lymphocytes (beta-ARtotal) was inversely correlated with the
      VO2 max (r = -0. 368; P < 0.05) and the VO2@VT (r = -0.359; P < 0.05). Similar
      relationships were also observed between the number of beta-AR in cell surface
      and both VO2 max (r = -0.491; P < 0.05) and VO2@VT (r = -0.498; P < 0.05).
      However, no correlation was obtained between the number of beta-AR in
      intracellular compartments and either VO2 max or VO2@VT. The beta2-AR mRNA level
      quantified by the use of competitive reverse transcription-polymerase chain
      reaction was inversely correlated with VO2@VT (r = -0.567; P < 0.05) and
      positively correlated with beta-ARtotal (r = 0.521; P < 0.05). These findings
      suggest that the beta-AR number in lymphocytes is inversely correlated with
      aerobic capacity. This relationship may be explained by downregulation of beta
      AR, including internalization with subsequent degradation of the receptors and
      inhibition of the beta-AR biosynthesis.

PMID- 9611164
TI  - Response of normal and osteoporotic human bone cells to mechanical stress in
      vitro.
AB  - Bone adapts to mechanical stress, and bone cell cultures from animal origin have
      been shown to be highly sensitive to mechanical stress in vitro. In this study,
      we tested whether bone cell cultures from human bone biopsies respond to stress
      in a similar manner as animal bone cells and whether bone cells from osteoporotic
      patients respond similarly to nonosteoporotic donors. Bone cell cultures were
      obtained as outgrowth from collagenase-stripped trabecular bone fragments from 17
      nonosteoporotic donors between 7 and 77 yr of age and from 6 osteoporotic donors
      between 42 and 72 yr of age. After passage, the cells were mechanically stressed
      by treatment with pulsating fluid flow (PFF; 0.7 +/- 0.03 Pa at 5 Hz for 1 h) to
      mimic the stress-driven flow of interstitial fluid through the bone canaliculi,
      which is likely the stimulus for mechanosensation in bone in vivo. Similar to
      earlier studies in rodent and chicken bone cells, the bone cells from
      nonosteoporotic donors responded to PFF with enhanced release of prostaglandin E2
      (PGE2) and nitric oxide as well as a reduced release of transforming growth
      factor-beta (TGF-beta). The upregulation of PGE2 but not the other responses
      continued for 24 h after 1 h of PFF treatment. The bone cells from osteoporotic
      donors responded in a similar manner as the nonosteoporotic donors except for the
      long-term PGE2 release. The PFF-mediated upregulation of PGE2 release during 24 h
      of postincubation after 1 h of PFF was significantly reduced in osteoporotic
      patients compared with six age-matched controls as well as with the whole
      nonosteoporotic group. These results indicate that enhanced release of PGE2 and
      nitric oxide, as well as reduced release of TGF-beta, is a characteristic
      response of human bone cells to fluid shear stress, similar to animal bone cells.
      The results also suggest that bone cells from osteoporotic patients may be
      impaired in their long-term response to mechanical stress.

PMID- 9611165
TI  - Short-term culture of ovine embryos modifies fetal myogenesis.
AB  - Certain reproductive techniques culture embryos in vitro; however, little is
      known about the impact of culture on fetal growth. Coculture of day 1 ovine
      zygotes on a bovine granulosa cell layer to blastocysts followed by transfer to
      synchronous recipients increased fetal weight by 11 and 40% at days 61 and 125,
      respectively, compared with the transfer of in vivo-produced blastocysts.
      Plantaris muscle weights were increased by 40% in cultured fetuses at day 125.
      Examination of myogenesis in plantaris muscle showed that primary fiber number
      was unchanged at day 61 by culture but that primary fiber area was increased
      significantly by 15 and 25% at days 61 and 125, respectively; secondary fiber
      area was increased by 40% at day 125 by culture, and the ratio of secondary to
      primary fiber numbers was 18-20% greater in the cultured groups compared with the
      controls at days 61 and 125. The results show that coculture of preimplantation
      embryos may alter myogenic programming. These changes may contribute to the
      abnormally large muscles observed in oversize fetuses.

PMID- 9611166
TI  - Anatomy of a revolution.

PMID- 9611167
TI  - Evidence for a role for AtMYB2 in the induction of the Arabidopsis alcohol
      dehydrogenase gene (ADH1) by low oxygen.
AB  - The transcription factor AtMYB2 binds to two sequence motifs in the promoter of
      the Arabidopsis ADH1 gene. The binding to the GT-motif (5'-TGGTTT-3') is
      essential for induction of ADH1 by low oxygen, while binding to the second motif,
      MBS-2, is not essential for induction. We show that AtMYB2 is induced by hypoxia
      with kinetics compatible with a role in the regulation of ADH1. Like ADH1, AtMYB2
      has root-limited expression. When driven by a constitutive promoter, AtMYB2 is
      able to transactivate ADH1 expression in transient assays in both Arabidopsis and
      Nicotiana plumbaginifolia protoplasts, and in particle bombardment of Pisum
      sativum leaves. Mutation of the GT-motif abolished binding of AtMYB2 and caused
      loss of activity of the ADH1 promoter in both transient assays and transgenic
      Arabidopsis plants. These results are consistent with AtMYB2 being a key
      regulatory factor in the induction of the ADH1 promoter by low oxygen.

PMID- 9611168
TI  - Arabidopsis mutants define an in vivo role for isoenzymes of aspartate
      aminotransferase in plant nitrogen assimilation.
AB  - Arabidopsis contains five isoenzymes of aspartate aminotransferase (AspAT)
      localized to the cytosol, chloroplast, mitochondria, or peroxisomes. To define
      the in vivo function of individual isoenzymes, we screened for Arabidopsis
      mutants deficient in either of the two major isoenzymes, cytosolic AAT2 or
      chloroplastic AAT3, using a native gel activity assay. In a screen of 8,000 M2
      seedlings, three independent mutants deficient in cytosolic AAT2 (aat2) and two
      independent mutants deficient in chloroplastic AAT3 (aat3) were isolated. Mapping
      of aat2 and aat3 mutations and the five AspAT genes (ASP1-ASP5) established
      associations as follows: the mutation affecting aat2 maps with and cosegregates
      with ASP2, one of two expressed genes for cytosolic AspAT; the mutation affecting
      aat3 maps to the same location as the ASP5 gene encoding chloroplastic AspAT.
      Phenotypic analysis of the aat2 and aat3 mutants revealed a dramatic aspartate
      related phenotype in one of the mutants deficient in cytosolic AAT2. The aat2-2
      mutant displays an 80% reduction in levels of aspartate transported in the phloem
      of light-grown plants, and a 50% reduction in levels of asparagine transported in
      dark-adapted plants. These results indicate that cytosolic AAT2 is the major
      isoenzyme controlling aspartate synthesized for nitrogen transport in the light,
      and that this aspartate pool is converted to asparagine when plants are dark
      adapted.

PMID- 9611169
TI  - A transgene encoding a plasma membrane H+-ATPase that confers acid resistance in
      Arabidopsis thaliana seedlings.
AB  - Proton pumps (H+-ATPases) are the primary active transport systems in the plasma
      membrane of higher plant cells. These enzymes are encoded by a large gene family
      expressed throughout the plant, with specific isoforms directed to various
      specialized cells. While their involvement in membrane energetics has been
      suggested by a large body of biochemical and physiological studies, a genetic
      analysis of their role in plants has not yet been performed. We report here that
      mutant Arabidopsis thaliana plants containing a phloem-specific transgene
      encoding a plasma membrane H+-ATPase with an altered carboxy terminus show
      improved growth at low pH during seedling development. These observations provide
      the first genetic evidence for a role of the plasma membrane H+-ATPase in
      cytoplasmic pH homeostasis in plants.

PMID- 9611170
TI  - Isolation of the GA-response mutant sly1 as a suppressor of ABI1-1 in Arabidopsis
      thaliana.
AB  - Seed dormancy and germination in higher plants are partially controlled by the
      plant hormones abscisic acid (ABA) and gibberellic acid (GA). ABA establishes
      dormancy during embryo maturation, whereas GA breaks dormancy and induces
      germination. Previous attempts to identify GA response genes were confounded
      because GA mutants are not expected to germinate and, unlike GA auxotrophs,
      should fail to be rescued by exogenous GA. Here, we describe a screen for
      suppressors of the ABA-insensitive mutant ABI1-1 that enriches for GA auxotrophs
      and GA-insensitive mutants. The vast majority (76%) of the suppressors of ABI1-1
      strongly resemble GA auxotrophs in that they are severely dwarfed and have dark
      green foliage and flowers with underdeveloped petals and stamen. Three isolates
      were alleles of the GA auxotroph ga1. The remaining severe dwarves were not
      rescued by GA and belong to a single complementation group that we designate sly1
      (Sleepy 1). The alleles of sly1 identified are the first recessive GA-insensitive
      mutations to reflect the full spectrum of GA-associated phenotypes, including the
      failure to germinate in the absence of the ABI1-1 lesion. Thus, we postulate that
      SLY1 is a key factor in GA reception.

PMID- 9611171
TI  - Coordination of phytochrome levels in phyB mutants of Arabidopsis as revealed by
      apoprotein-specific monoclonal antibodies.
AB  - Accumulating evidence indicates that individual members of the phytochrome family
      of photoreceptors have differential but interactive roles in controlling plant
      responses to light. To investigate possible cross-regulation of these receptors,
      we have identified monoclonal antibodies that specifically detect each of the
      five Arabidopsis phytochromes, phyA to phyE (phytochrome A holoprotein; PHYA,
      phytochrome A apoprotein; PHYA, phytochrome A gene; phyA, mutant allele of
      phytochrome A gene), on immunoblots and have used them to analyze the effects of
      phyA and phyB null mutations on the levels of all five family members. In phyB
      mutants, but not in phyA mutants, a four- to six-fold reduction in the level of
      phyC is observed in tissues grown either in the dark or in the light. Coordinate
      expression of phyB and phyC is induced in the phyB mutant background by the
      presence of a complementing PHYB transgene. However, in transgenic lines that
      overexpress phyB 15- to 20-fold, phyC is not similarly overexpressed. In these
      overexpressor lines, the levels of phyA, phyC, and phyD are increased two- to
      four-fold over normal in light-grown but not dark-grown seedlings. These
      observations indicate that molecular mechanisms for coordination or cross
      regulation of phytochrome levels are active in Arabidopsis and have implications
      for the interpretation of phytochrome mutants and overexpressor lines.

PMID- 9611172
TI  - Isolation of new Arabidopsis mutants with enhanced disease susceptibility to
      Pseudomonas syringae by direct screening.
AB  - To identify plant defense components that are important in restricting the growth
      of virulent pathogens, we screened for Arabidopsis mutants in the accession
      Columbia (carrying the transgene BGL2-GUS) that display enhanced disease
      susceptibility to the virulent bacterial pathogen Pseudomonas syringae pv.
      maculicola (Psm) ES4326. Among six (out of a total of 11 isolated) enhanced
      disease susceptibility (eds) mutants that were studied in detail, we identified
      one allele of the previously described npr1/nim1/sai1 mutation, which is affected
      in mounting a systemic acquired resistance response, one allele of the previously
      identified EDS5 gene, and four EDS genes that have not been previously described.
      The six eds mutants studied in detail (npr1-4, eds5-2, eds10-1, eds11-1, eds12-1,
      and eds13-1) displayed different patterns of enhanced susceptibility to a variety
      of phytopathogenic bacteria and to the obligate biotrophic fungal pathogen
      Erysiphe orontii, suggesting that particular EDS genes have pathogen-specific
      roles in conferring resistance. All six eds mutants retained the ability to mount
      a hypersensitive response and to restrict the growth of the avirulent strain Psm
      ES4326/avrRpt2. With the exception of npr1-4, the mutants were able to initiate a
      systemic acquired resistance (SAR) response, although enhanced growth of Psm
      ES4326 was still detectable in leaves of SAR-induced plants. The data presented
      here indicate that eds genes define a variety of components involved in limiting
      pathogen growth, that many additional EDS genes remain to be discovered, and that
      direct screens for mutants with altered susceptibility to pathogens are helpful
      in the dissection of complex pathogen response pathways in plants.

PMID- 9611173
TI  - Somatic embryogenesis in Arabidopsis thaliana is facilitated by mutations in
      genes repressing meristematic cell divisions.
AB  - Embryogenesis in plants can commence from cells other than the fertilized egg
      cell. Embryogenesis initiated from somatic cells in vitro is an attractive system
      for studying early embryonic stages when they are accessible to experimental
      manipulation. Somatic embryogenesis in Arabidopsis offers the additional
      advantage that many zygotic embryo mutants can be studied under in vitro
      conditions. Two systems are available. The first employs immature zygotic embryos
      as starting material, yielding continuously growing embryogenic cultures in
      liquid medium. This is possible in at least 11 ecotypes. A second, more efficient
      and reproducible system, employing the primordia timing mutant (pt allelic to
      hpt, cop2, and amp1), was established. A significant advantage of the pt mutant
      is that intact seeds, germinated in 2,4-dichlorophenoxyacetic acid (2, 4-D)
      containing liquid medium, give rise to stable embryonic cell cultures,
      circumventing tedious hand dissection of immature zygotic embryos. pt zygotic
      embryos are first distinguishable from wild type at early heart stage by a
      broader embryonic shoot apical meristem (SAM). In culture, embryogenic clusters
      originate from the enlarged SAMs. pt somatic embryos had all characteristic
      embryo pattern elements seen in zygotic embryos, but with higher and more
      variable numbers of cells. Embryogenic cell cultures were also established from
      seedling, of other mutants with enlarged SAMs, such as clavata (clv). pt clv
      double mutants showed additive effects on SAM size and an even higher frequency
      of seedlings producing embryogenic cell lines. pt clv double mutant plants had
      very short fasciated inflorescence stems and additive effects on the number of
      rosette leaves. This suggests that the PT and CLV genes act in independent
      pathways that control SAM size. An increased population of noncommitted SAM cells
      may be responsible for facilitated establishment of somatic embryogenesis in
      Arabidopsis.

PMID- 9611174
TI  - cot1: a regulator of Arabidopsis trichome initiation.
AB  - In Arabidopsis, the timing and spatial arrangement of trichome initiation is
      tightly regulated and requires the activity of the GLABROUS1 (GL1) gene. The
      COTYLEDON TRICHOME 1 (COT1) gene affects trichome initiation during late stages
      of leaf development and is described in this article. In the wild-type
      background, cot1 has no observable effect on trichome initiation. GL1
      overexpression in wild-type plants leads to a modest number of ectopic trichomes
      and to a decrease in trichome number on the adaxial leaf surface. The cot1
      mutation enhances GL1-overexpression-dependent ectopic trichome formation and
      also induces increased leaf trichome initiation. The expressivity of the cot1
      phenotype is sensitive to cot1 and 35S::GL1 gene dosage, and the most severe
      phenotypes are observed when cot1 and 35S::GL1 are homozygous. The COT1 locus is
      located on chromosome 2 15.3 cM north of er. Analysis of the interaction between
      cot1, try, and 35S::GL1 suggests that COT1 is part of a complex signal
      transduction pathway that regulates GL1-dependent adoption of the trichome cell
      fate.

PMID- 9611175
TI  - A genetic screen for modifiers of UFO meristem activity identifies three novel
      FUSED FLORAL ORGANS genes required for early flower development in Arabidopsis.
AB  - In a screen to identify novel genes required for early Arabidopsis flower
      development, we isolated four independent mutations that enhance the Ufo
      phenotype toward the production of filamentous structures in place of flowers.
      The mutants fall into three complementation groups, which we have termed FUSED
      FLORAL ORGANS (FFO) loci. ffo mutants have specific defects in floral organ
      separation and/or positioning; thus, the FFO genes identify components of a
      boundary formation mechanism(s) acting between developing floral organ primordia.
      FFO1 and FFO3 have specific functions in cauline leaf/stem separation and in
      first- and third-whorl floral organ separation, with FFO3 likely acting to
      establish and FFO1 to maintain floral organ boundaries. FFO2 acts at early floral
      stages to regulate floral organ number and positioning and to control organ
      separation within and between whorls. Plants doubly mutant for two ffo alleles
      display additive phenotypes, indicating that the FFO genes may act in separate
      pathways. Plants doubly mutant for an ffo gene and for ufo, lfy, or clv3 reveal
      that the FFO genes play roles related to those of UFO and LFY in floral meristem
      initiation and that FFO2 and FFO3 may act to control cell proliferation late in
      inflorescence development.

PMID- 9611176
TI  - The TERMINAL FLOWER2 (TFL2) gene controls the reproductive transition and
      meristem identity in Arabidopsis thaliana.
AB  - A new mutant of Arabidopsis thaliana that initiates flowering early and
      terminates the inflorescence with floral structures has been identified and named
      terminal flower2 (tfl2). While these phenotypes are similar to that of the
      terminal flower1 (tfl1) mutant, tfl2 mutant plants are also dwarfed in
      appearance, have reduced photoperiod sensitivity and have a more variable
      terminal flower structure. Under long-day and short-day growth conditions tfl1
      tfl2 double mutants terminate the inflorescence without development of lateral
      flowers; thus, unlike tfl1 single mutants the double mutant inflorescence
      morphology is not affected by day length. The enhanced phenotype of the double
      mutant suggests that TFL2 acts in a developmental pathway distinct from TFL1. The
      complex nature of the tfl2 single mutant phenotype suggests that TFL2 has a
      regulatory role more global than that of TFL1. Double mutant analysis of tfl2 in
      combination with mutant alleles of the floral meristem identity genes LEAFY and
      APETALA1 demonstrates that TFL2 function influences developmental processes
      controlled by APETALA1, but not those regulated by LEAFY. Thus, the TFL2 gene
      product appears to have a dual role in regulating meristem activity, one being to
      regulate the meristem response to light signals affecting the development of the
      plant and the other being the maintenance of inflorescence meristem identity.

PMID- 9611177
TI  - Genetic analysis of organ fusion in Arabidopsis thaliana.
AB  - Postgenital organ fusion occurs most commonly during reproductive development and
      is important in many angiosperms during genesis of the carpel. Although a number
      of mutants have been described that manifest ectopic organ fusion, little is
      known about the genes involved in regulating this process. In this article we
      describe the characterization of a collection of 29 Arabidopsis mutants showing
      an organ fusion phenotype. Mapping and complementation analyses revealed that the
      mutant alleles define nine different loci distributed throughout the Arabidopsis
      genome. Multiple alleles were isolated for the four complementation groups
      showing the strongest organ fusion phenotype while the remaining five
      complementation groups, all of which show only weak floral organ fusion, have a
      single representative allele. In addition to fusion events between aerial parts
      of the shoot, some mutants also show abnormal ovule morphology with adjacent
      ovules joined together at maturity. Many of the fusion mutants isolated have
      detectable differences in the rate at which chlorophyll can be extracted;
      however, in one case no difference could be detected between mutant and wild-type
      plants. In three mutant lines pollen remained unresponsive to contact with the
      mutant epidermis, demonstrating that organ fusion and pollen growth responses can
      be genetically separated from one another.

PMID- 9611178
TI  - Selection of T-DNA-tagged male and female gametophytic mutants by segregation
      distortion in Arabidopsis.
AB  - As a strategy for the identification of T-DNA-tagged gametophytic mutants, we
      have used T-DNA insertional mutagenesis based on screening for distorted
      segregation ratios by antibiotic selection. Screening of approximately 1000
      transgenic Arabidopsis families led to the isolation of eight lines showing
      reproducible segregation ratios of approximately 1:1, suggesting that these lines
      are putative gametophytic mutants caused by T-DNA insertion at a single locus.
      Genetic analysis of T-DNA transmission through reciprocal backcrosses with wild
      type showed severe reductions in genetic transmission of the T-DNA through the
      male and/or female gametes. Direct evidence for mutant phenotypes in these lines
      was investigated by DAPI staining of mature pollen grains and by the analysis of
      seed set and embryo sac morphology in cleared ovules. One line, termed limpet
      pollen, showed a novel pollen phenotype in that the generative cell failed to
      migrate inward after pollen mitosis I, such that the generative or sperm cells
      remained against the pollen wall. Two other lines, andarta and tistrya, were
      defective in female transmission and showed an early arrest of embryo sac
      development with the viable megaspore not initiating the nuclear division cycles.
      These data demonstrate the efficacy of a segregation ratio distortion strategy
      for the identification of T-DNA-tagged gametophytic mutants in Arabidopsis.

PMID- 9611179
TI  - Activation of latent transgenes in Arabidopsis using a hybrid transcription
      factor.
AB  - A hybrid transcription factor comprising a fusion of the DNA-binding domain of
      Saccharomyces cerevisiae GAL4 and the transcription activation domain of maize C1
      was expressed in stably transformed Arabidopsis. Additional transgenic lines were
      created containing test genes controlled by a synthetic promoter consisting of
      concatemeric copies of the cis-acting site recognized by GAL4 (UASG) fused to a
      minimal promoter. The GAL4/C1 effector line was crossed to two lines containing a
      synthetic promoter/GUS fusion. Both histochemical staining and GUS activity
      assays indicate strong activation of GUS expression was achieved only after
      crossing. The GAL4/C1 effector line was also crossed to 15 lines containing a
      synthetic promoter/antisense adenylosuccinate synthetase gene. Severely retarded
      growth, and in some cases lethality, was observed in 40% of the F1 lines. This
      system of activation by crossing is generally useful for activating expression of
      test transgenes.

PMID- 9611180
TI  - Major chromosomal rearrangements induced by T-DNA transformation in Arabidopsis.
AB  - We show that major chromosomal rearrangements can occur upon T-DNA transformation
      of Arabidopsis thaliana. In the ACL4 line, two T-DNA insertion loci were found;
      one is a tandem T-DNA insert in a head-to-head orientation, and the other is a
      truncated insert with only the left part of the T-region. The four flanking DNA
      regions were isolated and located on the Arabidopsis chromosomes; for both
      inserts, one side of the T-DNA maps to chromosome 2, whereas the other side maps
      to chromosome 3. Both chromosome 3 flanking regions map to the same location,
      despite a 1.4-kb deletion at this point, whereas chromosome 2 flanking regions
      are located 40 cM apart on the bottom arm of chromosome 2. These results strongly
      suggest a reciprocal translocation between chromosomes 2 and 3, with the
      breakpoints located at the T-DNA insertion sites. The interchanged fragments
      roughly correspond to the 20-cM distal ends of both chromosomes. Moreover, a
      large inversion, spanning 40 cM on the genetic map, occurs on the bottom arm of
      chromosome 2. This was confirmed by genetic analyses that demonstrated a strong
      reduction of recombination in the inverted region. Models for T-DNA integration
      and the consequences for T-DNA tagging are discussed in light of these results.

PMID- 9611181
TI  - Gene silencing and homology-dependent gene silencing in Arabidopsis: genetic
      modifiers and DNA methylation.
AB  - Transgenes inserted into the plant genome can become inactive (gene silencing) or
      result in silencing of homologous cellular genes [homology-dependent gene
      silencing (HDG silencing)]. In an earlier study we reported HDG silencing of
      chalcone synthase (CHS) in Arabidopsis. This study concerns genetic revertants of
      one of the CHS HDG-silencing transgenic homozygotes. Two monogenic recessive
      trans-acting mutations (hog1 and ddm1) that impair gene silencing and HDG
      silencing were identified. These mutations reduce genomic DNA methylation and
      affect the quantity and size of CHS mRNA. These results imply that DNA
      methylation is necessary for both gene silencing and HDG silencing. Two further
      monogenic, trans-acting, recessive mutations (sil1 and sil2) reduce gene
      silencing but not HDG silencing. The existence of this mutant class shows that
      gene silencing involves genes that are not necessary for HDG silencing. A further
      mutant (Catt) was isolated and has an attenuated HDG-silencing T-DNA.

PMID- 9611182
TI  - Members of the Arabidopsis actin gene family are widely dispersed in the genome.
AB  - Plant genomes are subjected to a variety of DNA turnover mechanisms that are
      thought to result in rapid expansion and presumable contraction of gene copy
      number. The evolutionary history of the 10 actin genes in Arabidopsis thaliana is
      well characterized and can be traced to the origin of vascular plant genomes.
      Knowledge about the genomic position of each actin gene may be the key to tracing
      landmark genomic duplication events that define plant families or genera and
      facilitate further mutant isolation. All 10 actin genes were mapped by following
      the segregation of cleaved amplified polymorphisms between two ecotypes and
      identifying actin gene locations among yeast artificial chromosomes. The
      Arabidopsis actin genes are widely dispersed on four different chromosomes (1, 2,
      3, and 5). Even the members of three closely related and recently duplicated
      pairs of actin genes are unlinked. Several other cytoskeletal genes (profilins,
      tubulins) that might have evolved in concert with actins were also mapped, but
      showed few patterns consistent with that evolutionary history. Thus, the events
      that gave rise to the actin gene family have been obscured either by the
      duplication of very small genic fragments or by extensive rearrangement of the
      genome.

PMID- 9611184
TI  - Characterization of the putative transposase mRNA of Tag1, which is ubiquitously
      expressed in Arabidopsis and can be induced by Agrobacterium-mediated
      transformation with dTag1 DNA.
AB  - Tag1 is an autonomous transposable element of Arabidopsis thaliana. Tag1
      expression was examined in two ecotypes of Arabidopsis (Columbia and No-0) that
      were transformed with CaMV 35S-Tag1-GUS DNA. These ecotypes contain no endogenous
      Tag1 elements. A major 2.3-kb and several minor transcripts were detected in all
      major organs of the plants. The major transcript encoded a putative transposase
      of 84.2 kD with two nuclear localization signal sequences and a region conserved
      among transposases of the Ac or hAT family of elements. The abundance of Tag1
      transcripts varied among transgenic lines and did not correlate with somatic
      excision frequency or germinal reversion rates, suggesting that factors other
      than transcript levels control Tag1 excision activity. In untransformed plants of
      the Landsberg ecotype, which contain two endogenous Tag1 elements, no Tag1
      transcripts were detected. Agrobacterium-mediated transformation of these
      Landsberg plants with a defective 1.4-kb Tag1 element resulted in the appearance
      of full-length Tag1 transcripts from the endogenous elements. Transformation with
      control DNA containing no Tag1 sequences did not activate endogenous Tag1
      expression. These results indicate that Agrobacterium-mediated transformation
      with dTag1 can activate the expression of Tag1.

PMID- 9611183
TI  - Molecular organization of the 20S proteasome gene family from Arabidopsis
      thaliana.
AB  - The 20S proteasome is the proteolytic complex in eukaryotes responsible for
      degrading short-lived and abnormal intracellular proteins, especially those
      targeted by ubiquitin conjugation. The 700-kD complex exists as a hollow cylinder
      comprising four stacked rings with the catalytic sites located in the lumen. The
      two outer rings and the two inner rings are composed of seven different alpha and
      beta polypeptides, respectively, giving an alpha7/beta7/beta7/alpha7 symmetric
      organization. Here we describe the molecular organization of the 20S proteasome
      from the plant Arabidopsis thaliana. From an analysis of a collection of cDNA and
      genomic clones, we identified a superfamily of 23 genes encoding all 14 of the
      Arabidopsis proteasome subunits, designated PAA-PAG and PBA-PBG for Proteasome
      Alpha and Beta subunits A-G, respectively. Four of the subunits likely are
      encoded by single genes, and the remaining subunits are encoded by families of at
      least 2 genes. Expression of the alpha and beta subunit genes appears to be
      coordinately regulated. Three of the nine Arabidopsis proteasome subunit genes
      tested, PAC1 (alpha3), PAE1 (alpha5) and PBC2 (beta3), could functionally replace
      their yeast orthologs, providing the first evidence for cross-species
      complementation of 20S subunit genes. Taken together, these results demonstrate
      that the 20S proteasome is structurally and functionally conserved among
      eukaryotes and suggest that the subunit arrangement of the Arabidopsis 20S
      proteasome is similar if not identical to that recently determined for the yeast
      complex.

PMID- 9611185
TI  - Potential retroviruses in plants: Tat1 is related to a group of Arabidopsis
      thaliana Ty3/gypsy retrotransposons that encode envelope-like proteins.
AB  - Tat1 was originally identified as an insertion near the Arabidopsis thaliana SAM1
      gene. We provide evidence that Tat1 is a retrotransposon and that previously
      described insertions are solo long terminal repeats (LTRs) left behind after the
      deletion of coding regions of full-length elements. Three Tat1 insertions were
      characterized that have retrotransposon features, including a primer binding site
      complementary to an A. thaliana asparagine tRNA and an open reading frame (ORF)
      with approximately 44% amino acid sequence similarity to the gag protein of the
      Zea mays retrotransposon Zeon-1. Tat1 elements have large, polymorphic 3'
      noncoding regions that may contain transduced DNA sequences; a 477-base insertion
      in the 3' noncoding region of the Tat1-3 element contains part of a related
      retrotransposon and sequences similar to the nontranslated leader sequence of AT
      P5C1, a gene for pyrroline-5-carboxylate reductase. Analysis of DNA sequences
      generated by the A. thaliana genome project identified 10 families of Ty3/gypsy
      retrotransposons, which share up to 51 and 62% amino-acid similarity to the ORFs
      of Tat1 and the A. thaliana Athila element, respectively. Phylogenetic analyses
      resolved the plant Ty3/gypsy elements into two lineages, one of which includes
      homologs of Tat1 and Athila. Four families of A. thaliana elements within the
      Tat/Athila lineage encode a conserved ORF after integrase at a position occupied
      by the envelope gene in retroviruses and in some insect Ty3/gypsy
      retrotransposons. Like retroviral envelope genes, this ORF encodes a
      transmembrane domain and, in some insertions, a putative secretory signal
      sequence. This suggests that Tat/Athila retrotransposons may produce enveloped
      virions and may be infectious.

PMID- 9611186
TI  - Detection of deleterious genotypes in multigenerational studies. I. Disruptions
      in individual Arabidopsis actin genes.
AB  - Plant actins are involved in numerous cytoskeletal processes effecting plant
      development, including cell division plane determination, cell elongation, and
      cell wall deposition. Arabidopsis thaliana has five ancient subclasses of actin
      with distinct patterns of spatial and temporal expression. To test their
      functional roles, we identified insertion mutants in three Arabidopsis actin
      genes, ACT2, ACT4, and ACT7, representing three subclasses. Adult plants
      homozygous for the act2-1, act4-1, and act7-1 mutant alleles appear to be robust,
      morphologically normal, and fully fertile. However, when grown as populations
      descended from a single heterozygous parent, all three mutant alleles were found
      at extremely low frequencies relative to the wild-type in the F2 generation.
      Thus, all three mutant alleles appear to be deleterious. The act2-1 mutant allele
      was found at normal frequencies in the F1, but at significantly lower frequencies
      than expected in the F2 and F3 generations. These data suggest that the
      homozygous act2-1/act2-1 mutant adult plants have a reduced fitness in the 2N
      sporophytic portion of the life cycle, consistent with the vegetative expression
      of ACT2. These data are interpreted in light of the extreme conservation of plant
      actin subclasses and genetic redundancy.

PMID- 9611187
TI  - Detection of deleterious genotypes in multigenerational studies. II. Theoretical
      and experimental dynamics with selfing and selection.
AB  - A mathematical model was developed to help interpret genotype and allele
      frequency dynamics in selfing populations, with or without apomixis. Our analysis
      provided explicit time-dependent solutions for the frequencies at diallelic loci
      in diploid populations under any combination of fertility, viability, and gametic
      selection through meiotic drive. With no outcrossing, allelic variation is always
      maintained under gametic selection alone, but with any fertility or viability
      differences, variation will ordinarily be maintained if and only if the net
      fitness (fertility x viability) of heterozygotes exceeds that of both homozygotes
      by a substantial margin. Under pure selfing and Mendelian segregation,
      heterozygotes must have a twofold fitness advantage; the level of overdominance
      necessary to preserve genetic diversity declines with apomixis, and increases
      with segregation distortion if this occurs equally and independently in male and
      female gametes. A case study was made of the Arabidopsis act2-1 actin mutant over
      multiple generations initiated from a heterozygous plant. The observed genotypic
      frequency dynamics were consistent with those predicted by our model for a
      deleterious, incompletely recessive mutant in either fertility or viability. The
      theoretical framework developed here should be very useful in dissecting the
      form(s) and strength of selection on diploid genotypes in populations with
      negligible levels of outcrossing.

PMID- 9611188
TI  - The molecular basis of quantitative genetic variation in central and secondary
      metabolism in Arabidopsis.
AB  - To find the genes controlling quantitative variation, we need model systems where
      functional information on physiology, development, and gene regulation can guide
      evolutionary inferences. We mapped quantitative trait loci (QTLs) influencing
      quantitative levels of enzyme activity in primary and secondary metabolism in
      Arabidopsis. All 10 enzymes showed highly significant quantitative genetic
      variation. Strong positive genetic correlations were found among activity levels
      of 5 glycolytic enzymes, PGI, PGM, GPD, FBP, and G6P, suggesting that enzymes
      with closely related metabolic functions are coregulated. Significant QTLs were
      found influencing activity of most enzymes. Some enzyme activity QTLs mapped very
      close to known enzyme-encoding loci (e.g., hexokinase, PGI, and PGM). A
      hexokinase QTL is attributable to cis-acting regulatory variation at the AtHXK1
      locus or a closely linked regulatory locus, rather than polypeptide sequence
      differences. We also found a QTL on chromosome IV that may be a joint regulator
      of GPD, PGI, and G6P activity. In addition, a QTL affecting PGM activity maps
      within 700 kb of the PGM-encoding locus. This QTL is predicted to alter starch
      biosynthesis by 3.4%, corresponding with theoretical models, suggesting that QTLs
      reflect pleiotropic effects of mutant alleles.

PMID- 9611189
TI  - Analysis of natural allelic variation at flowering time loci in the Landsberg
      erecta and Cape Verde Islands ecotypes of Arabidopsis thaliana.
AB  - We have analyzed the flowering behavior of two Arabidopsis ecotypes: the
      laboratory strain Landsberg erecta (Ler) and an ecotype from the tropical Cape
      Verde Islands (Cvi). They differ little in their flowering phenotypes and in
      their responses to photoperiod length changes and to vernalization treatment.
      However, segregating populations derived from crosses between them showed a much
      larger variation. An approach of quantitative trait locus (QTL) mapping in
      recombinant inbred lines (RILs) grown under three environments differing in day
      length and/or vernalization treatment has been used to detect and locate
      flowering loci. Four main QTLs were identified, designated early day-length
      insensitive (EDI), flowering F, G, and H (FLF, FLG, and FLH, respectively), to
      which most of the flowering behavior differences could be attributed. To further
      characterize the individual loci, near isogenic lines were constructed by
      introgressing Cvi early alleles of EDI and FLH into the Ler genetic background.
      EDI-Cvi alleles produce earliness under both long- and short-day photoperiods,
      rendering Ler plants almost day-length neutral. In addition, RILs were selected
      to analyze FLF and FLG. These loci interact epistatically and RILs carrying late
      alleles at FLF and FLG were very responsive to vernalization and showed an
      increased response to photoperiod length changes. The possible role of these loci
      for the control of flowering is discussed in the context of the current
      Arabidopsis model.

PMID- 9611190
TI  - Molecular evolution of genes controlling petal and stamen development:
      duplication and divergence within the APETALA3 and PISTILLATA MADS-box gene
      lineages.
AB  - The specification of floral organ identity in the higher dicots depends on the
      function of a limited set of homeotic genes, many of them members of the MADS-box
      gene family. Two such genes, APETALA3 (AP3) and PISTILLATA (PI), are required for
      petal and stamen identity in Arabidopsis; their orthologs in Antirrhinum exhibit
      similar functions. To understand how changes in these genes may have influenced
      the morphological evolution of petals and stamens, we have cloned twenty-six
      homologs of the AP3 and PI genes from two higher eudicot and eleven lower eudicot
      and magnolid dicot species. The sequences of these genes reveal the presence of
      characteristic PI- and AP3-specific motifs. While the PI-specific motif is found
      in all of the PI genes characterized to date, the lower eudicot and magnolid
      dicot AP3 homologs contain distinctly different motifs from those seen in the
      higher eudicots. An analysis of all the available AP3 and PI sequences uncovers
      multiple duplication events within each of the two gene lineages. A major
      duplication event in the AP3 lineage coincides with the base of the higher
      eudicot radiation and may reflect the evolution of a petal-specific AP3 function
      in the higher eudicot lineage.

PMID- 9611191
TI  - Multiple recombination events maintain sequence identity among members of the
      nitrogenase multigene family in Rhizobium etli.
AB  - A distinctive characteristic of the Rhizobium genome is the frequent finding of
      reiterated sequences, which often constitute multigene families. Interestingly,
      these families usually maintain a high degree of nucleotide sequence identity. It
      is commonly assumed that apparent gene conversion between reiterated elements
      might lead to concerted variation among members of a multigene family. However,
      the operation of this mechanism has not yet been demonstrated in the
      Rhizobiaceae. In this work, we employed different genetic constructions to
      address the role of apparent gene conversion as a homogenizing mechanism between
      members of the plasmid-located nitrogenase multigene family in Rhizobium etli.
      Our results show that a 28-bp insertion into one of the nitrogenase reiterations
      can be corrected by multiple recombination events, including apparent gene
      conversion. The correction process was dependent on the presence of both a wild
      type recA gene and wild-type copies of the nitrogenase reiterations. Frequencies
      of apparent gene conversion to the wild-type nitrogenase reiterations were the
      same when the insertion to be corrected was located either in cis or in trans,
      indicating that this event frequently occurs through intermolecular interactions.
      Interestingly, a high frequency of multiple crossovers was observed, suggesting
      that these large plasmid molecules are engaging repeatedly in recombination
      events, in a situation akin to phage recombination or recombination among small,
      high-copy number plasmids.

PMID- 9611192
TI  - A nucleolar protein that affects mating efficiency in Saccharomyces cerevisiae by
      altering the morphological response to pheromone.
AB  - SSF1 and SSF2 are redundant essential yeast genes that, when overexpressed,
      increase the mating efficiency of cells containing a defective Ste4p Gbeta
      subunit. To identify the precise function of these genes in mating, different
      responses to pheromone were assayed in cells that either lacked or overexpressed
      SSF gene products. Cells containing null alleles of both SSF1 and SSF2 displayed
      the normal transcriptional induction response to pheromone but were unable to
      form mating projections. Overexpression of SSF1 conferred the ability to form
      mating projections on cells containing a temperature-sensitive STE4 allele, but
      had only a small effect on transcriptional induction. SSF1 overexpression
      preferentially increased the mating efficiency of a strain containing a null
      allele of SPA2, a gene that functions specifically in cell morphology. To
      investigate whether Ssf1p plays a direct physical role in mating projection
      formation, its subcellular location was determined. An Ssf1p-GFP fusion was found
      to localize to the nucleolus, implying that the role of SSF gene products in
      projection formation is indirect. The region of Ssf1p-GFP localization in cells
      undergoing projection formation was larger and more diffuse, and was often
      present in a specific orientation with respect to the projection. Although the
      function of Ssf1p appears to originate in the nucleus, it is likely that it
      ultimately acts on one or more of the proteins that is directly involved in the
      morphological response to pheromone. Because many of the proteins required for
      projection formation during mating are also required for bud formation during
      vegetative growth, regulation of the activity or amount of one or more of these
      proteins by Ssf1p could explain its role in both mating and dividing cells.

PMID- 9611193
TI  - Mutational analysis of the yeast DEAH-box splicing factor Prp16.
AB  - Prp16 is an essential yeast splicing factor that catalyzes RNA-dependent
      hydrolysis of nucleoside triphosphates. Prp16 is a member of the DEAH-box protein
      family, which is defined by six collinear sequence motifs. The importance of
      residues within four of the conserved motifs was assessed by alanine-scanning
      mutagenesis. Mutant alleles of PRP16 were tested for in vivo function by
      complementation of a Deltaprp16 null strain. In motif I (GETGSGKT), alanine
      substitutions at Gly-378, Lys-379, and Thr-380 were lethal, whereas replacement
      of the amino acids in positions 373-377 were viable. In the signature DEAH-box
      (motif II), Asp-473 and Glu-474 were essential, whereas the H476A mutant was
      viable. The S505A and T507A mutants in motif III (SAT) were viable. In motif VI
      (QRSGRAGRTAPG), mutants Q685A, R686A, G688A, R689A, and R692A were lethal,
      whereas G691A, P695A, and G696A supported growth. Instructive structure-function
      relationships were established by conservative substitutions at essential
      residues identified by alanine scan. Overexpression of nonviable alleles impaired
      the growth of wild-type PRP16 cells. Deletion analysis of the 1071-amino-acid
      Prp16 protein revealed that the N-terminal 204 amino acids and the C-terminal 100
      residues were dispensable for PRP16 function in vivo. These studies provide an
      instructive framework for functional analysis of other DEAH-box splicing factors.

PMID- 9611194
TI  - Meiotic chromosome morphology and behavior in zip1 mutants of Saccharomyces
      cerevisiae.
AB  - The yeast Zip1 protein (Zip1p) is a component of the central region of the
      synaptonemal complex (SC). Zip1p is predicted to form a dimer consisting of a
      coiled-coil domain flanked by globular domains. To analyze the organization of
      Zip1p within the SC, in-frame deletions of ZIP1 were constructed and analyzed.
      The results demonstrate that the C terminus but not the N terminus of Zip1p is
      required for its localization to chromosomes. Deletions in the carboxy half of
      the predicted coiled-coil region cause decreases in the width of the SC. Based on
      these results, a model for the organization of Zip1p within the SC is proposed.
      zip1 deletion mutations were also examined for their effects on sporulation,
      spore viability, crossing over, and crossover interference. The results
      demonstrate that the extent of synapsis is positively correlated with the levels
      of spore viability, crossing over, and crossover interference. In contrast, the
      role of Zip1p in synapsis is separable from its role in meiotic cell cycle
      progression. zip1 mutants display interval-specific effects on crossing over.

PMID- 9611195
TI  - A high copy suppressor screen reveals genetic interactions between BET3 and a new
      gene. Evidence for a novel complex in ER-to-Golgi transport.
AB  - The BET3 gene in the yeast Saccharomyces cerevisiae encodes a 22-kD hydrophilic
      protein that is required for vesicular transport between the ER and Golgi
      complex. To gain insight into the role of Bet3p, we screened for genes that
      suppress the growth defect of the temperature-sensitive bet3 mutant at 34
      degrees. This high copy suppressor screen resulted in the isolation of a new
      gene, called BET5. BET5 encodes an essential 18-kD hydrophilic protein that in
      high copy allows growth of the bet3-1 mutant, but not other ER accumulating
      mutants. This strong and specific suppression is consistent with the fact that
      Bet3p and Bet5p are members of the same complex. Using PCR mutagenesis, we
      generated a temperature-sensitive mutation in BET5 (bet5-1) that blocks the
      transport of carboxypeptidase Y to the vacuole and prevents secretion of the
      yeast pheromone alpha-factor at 37 degrees. The precursor forms of these proteins
      that accumulate in this mutant are indicative of a block in membrane traffic
      between the ER and Golgi apparatus. High copy suppressors of the bet5-1 mutant
      include several genes whose products are required for ER-to-Golgi transport
      (BET1, SEC22, USO1 and DSS4) and the maintenance of the Golgi (ANP1). These
      findings support the hypothesis that Bet5p acts in conjunction with Bet3p to
      mediate a late stage in ER-to-Golgi transport. The identification of mammalian
      homologues of Bet3p and Bet5p implies that the Bet3p/Bet5p complex is highly
      conserved in evolution.

PMID- 9611197
TI  - Modulation of tubulin polypeptide ratios by the yeast protein Pac10p.
AB  - Normal assembly and function of microtubules require maintenance of the proper
      levels of several proteins, including the tubulin polypeptides themselves. For
      example, in yeast a significant excess of beta-tubulin causes rapid microtubule
      disassembly and subsequent cell death. Even the modest excess of beta-tubulin
      produced by genetic alterations such as deletion of the minor alpha-tubulin gene
      TUB3 affects cell growth and can confer microtubule phenotypes. We show here that
      the levels of the yeast protein Pac10p affect the relative levels of the tubulin
      polypeptides. Cells deleted for PAC10 have the same phenotypes as do cells that
      express reduced levels of alpha-tubulin or Rbl2p, two proteins that bind beta
      tubulin. Conversely, overexpression of Pac10p enhances the ability of alpha
      tubulin or Rbl2p to suppress the lethality associated with excess beta-tubulin.
      However, Pac10p is itself not a beta-tubulin binding protein. Pac10 null cells
      show a 30% decrease in the ratio of alpha-tubulin to beta-tubulin. The results
      suggest that Pac10p modulates the level of alpha-tubulin in the cell, and so
      influences microtubule morphogenesis and tubulin metabolism.

PMID- 9611196
TI  - Involvement of protein N-glycosyl chain glucosylation and processing in the
      biosynthesis of cell wall beta-1,6-glucan of Saccharomyces cerevisiae.
AB  - beta-1,6-Glucan plays a key structural role in the yeast cell wall. Of the genes
      involved in its biosynthesis, the activity of Cwh41p is known, i.e., the
      glucosidase I enzyme of protein N-chain glucose processing. We therefore examined
      the effects of N-chain glucosylation and processing mutants on beta-1,6-glucan
      biosynthesis and show that incomplete N-chain glucose processing results in a
      loss of beta-1,6-glucan, demonstrating a relationship between N-chain
      glucosylation/processing and beta-1,6-glucan biosynthesis. To explore the
      involvement of other N-chain-dependent events with beta-1,6-glucan synthesis, we
      investigated the Saccharomyces cerevisiae KRE5 and CNE1 genes, which encode
      homologs of the "quality control" components UDP-Glc:glycoprotein
      glucosyltransferase and calnexin, respectively. We show that the essential
      activity of Kre5p is separate from its possible role as a UDP-Glc:glycoprotein
      glucosyltransferase. We also observe a approximately 30% decrease in beta-1,6
      glucan upon disruption of the CNE1 gene, a phenotype that is additive with other
      beta-1,6-glucan synthetic mutants. Analysis of the cell wall anchorage of the
      mannoprotein alpha-agglutinin suggests the existence of two beta-1,6-glucan
      biosynthetic pathways, one N-chain dependent, the other involving protein
      glycosylphosphatidylinositol modification.

PMID- 9611198
TI  - Ion tolerance of Saccharomyces cerevisiae lacking the Ca2+/CaM-dependent
      phosphatase (calcineurin) is improved by mutations in URE2 or PMA1.
AB  - Calcineurin is a conserved, Ca2+/CaM-stimulated protein phosphatase required for
      Ca2+-dependent signaling in many cell types. In yeast, calcineurin is essential
      for growth in high concentrations of Na+, Li+, Mn2+, and OH-, and for maintaining
      viability during prolonged treatment with mating pheromone. In contrast, the
      growth of calcineurin-mutant yeast is better than that of wild-type cells in the
      presence of high concentrations of Ca2+. We identified mutations that suppress
      multiple growth defects of calcineurin-deficient yeast (cnb1Delta or cna1Delta
      cna2Delta). Mutations in URE2 suppress the sensitivity of calcineurin mutants to
      Na+, Li+, and Mn2+, and increase their survival during treatment with mating
      pheromone. ure2 mutations require both the transcription factor Gln3p and the Na+
      ATPase Pmr2p to confer Na+ and Li+ tolerance. Mutations in PMA1, which encodes
      the yeast plasma membrane H+-ATPase, also suppress many growth defects of
      calcineurin mutants. pma1 mutants display growth phenotypes that are opposite to
      those of calcineurin mutants; they are resistant to Na+, Li+, and Mn2+, and
      sensitive to Ca2+. We also show that calcineurin mutants are sensitive to
      aminoglycoside antibiotics such as hygromycin B while pma1 mutants are more
      resistant than wild type. Furthermore, pma1 and calcineurin mutations have
      antagonistic effects on intracellular [Na+] and [Ca2+]. Finally, we show that
      yeast expressing a constitutively active allele of calcineurin display pma1-like
      phenotypes, and that membranes from these yeast have decreased levels of Pma1p
      activity. These studies further characterize the roles that URE2 and PMA1 play in
      regulating intracellular ion homeostasis.

PMID- 9611199
TI  - Mot3, a Zn finger transcription factor that modulates gene expression and
      attenuates mating pheromone signaling in Saccharomyces cerevisiae.
AB  - In the yeast Saccharomyces cerevisiae, mating pheromone response is initiated by
      activation of a G protein- and mitogen-activated protein (MAP) kinase-dependent
      signaling pathway and attenuated by several mechanisms that promote adaptation or
      desensitization. To identify genes whose products negatively regulate pheromone
      signaling, we screened for mutations that suppress the hyperadaptive phenotype of
      wild-type cells overexpressing signaling-defective G protein beta subunits. This
      identified recessive mutations in MOT3, which encodes a nuclear protein with two
      Cys2-His2 Zn fingers. MOT3 was found to be a dosage-dependent inhibitor of
      pheromone response and pheromone-induced gene expression and to require an intact
      signaling pathway to exert its effects. Several results suggested that Mot3
      attenuates expression of pheromone-responsive genes by mechanisms distinct from
      those used by the negative transcriptional regulators Cdc36, Cdc39, and Mot2.
      First, a Mot3-lexA fusion functions as a transcriptional activator. Second, Mot3
      is a dose-dependent activator of several genes unrelated to pheromone response,
      including CYC1, SUC2, and LEU2. Third, insertion of consensus Mot3 binding sites
      (C/A/T)AGG(T/C)A activates a promoter in a MOT3-dependent manner. These findings,
      and the fact that consensus binding sites are found in the 5' flanking regions of
      many yeast genes, suggest that Mot3 is a globally acting transcriptional
      regulator. We hypothesize that Mot3 regulates expression of factors that
      attenuate signaling by the pheromone response pathway.

PMID- 9611200
TI  - The transcriptional activator Imp2p maintains ion homeostasis in Saccharomyces
      cerevisiae.
AB  - Yeast cells deficient in the transcriptional activator Imp2p are viable, but
      display marked hypersensitivity to a variety of oxidative agents. We now report
      that imp2 null mutants are also extremely sensitive to elevated levels of the
      monovalent ions, Na+ and Li+, as well as to the divalent ions Ca2+, Mn2+, Zn2+,
      and Cu2+, but not to Cd2+, Mg2+, Co2+, Ni2+, and Fe2+, as compared to the parent
      strain. We next searched for multicopy suppressor genes that would allow the
      imp2Delta mutant to grow under high salt conditions. Two genes that independently
      restored normal salt-resistance to the imp2Delta mutant, ENA1 and HAL3, were
      isolated. ENA1 encodes a P-type ion pump involved in monovalent ion efflux from
      the cell, while HAL3 encodes a protein required for activating the expression of
      Ena1p. Neither ENA1 nor HAL3 gene expression was positively regulated by Imp2p.
      Moreover, the imp2 ena1 double mutant was exquisitely sensitive to Na+/Li+
      cations, as compared to either single mutant, implying that Imp2p mediates
      Na+/Li+ cation homeostasis independently of Ena1p.

PMID- 9611201
TI  - Sir- and silencer-independent disruption of silencing in Saccharomyces by Sas10p.
AB  - A promoter fusion library of Saccharomyces cerevisiae genes was used to exploit
      phenotypes associated with altered protein dosage. We identified a novel gene,
      SAS10, by the ability of Sas10p, when overproduced, to disrupt silencing. The
      predicted Sas10p was 70,200 kD and strikingly rich in charged amino acids. Sas10p
      was exclusively nuclear in all stages of the cell cycle. Overproduction of Sas10p
      caused derepression of mating type genes at both HML and HMR, as well as of URA3,
      TRP1, and ADE2 when inserted near a telomere or at HMR or the rDNA locus.
      Repressed genes not associated with silenced chromatin were unaffected. Sas10p
      was essential for viability, and the termination point following Sas10p depletion
      was as large budded cells. Remarkably, Sas10p overproduction disrupted silencing
      even under conditions that bypassed the requirement for Sir proteins, ORC, and
      Rap1p in silencing. These data implied that Sas10p function was intimately
      connected with the structure of silenced chromatin.

PMID- 9611202
TI  - The mod-A suppressor of nonallelic heterokaryon incompatibility in Podospora
      anserina encodes a proline-rich polypeptide involved in female organ formation.
AB  - Vegetative incompatibility in fungi results from the control of heterokaryon
      formation by the genes present at het loci. Coexpression of antagonistic het
      genes in the same hyphae leads to a lethal process. In Podospora anserina, self
      incompatible strains containing nonallelic incompatible genes in the same nucleus
      are inviable as the result of a growth arrest and a lytic process. Mutations in
      suppressor genes (mod genes) can restore the viability. These mod mutations also
      interfere with developmental processes, which suggests common steps between the
      incompatibility reaction and cellular differentiation. The mod-A locus,
      responsible for growth arrest in the self-incompatible strains, is also involved
      in the control of the development of female organs. The mod-A gene was isolated.
      An open reading frame 687 amino acids long was identified. The MOD-A-encoded
      polypeptide is rich in proline residues, which are clustered in a domain
      containing a motif that displays similarity to SH3-binding motifs, which are
      known to be involved in protein-protein interactions. Construction of a strain
      deleted for mod-A confirmed that the product of this gene involved in
      differentiation is a key regulator of growth arrest associated with vegetative
      incompatibility.

PMID- 9611203
TI  - Genetics of the deflagellation pathway in Chlamydomonas.
AB  - Signal-induced deflagellation in Chlamydomonas involves Ca2+-activated breakage
      of the nine outer-doublet axonemal microtubules at a specific site in the
      flagellar transition zone. In this study, we isolated 13 new deflagellation
      mutants that can be divided into two phenotypic classes, the Adf class and the Fa
      class. Cells with the Adf deflagellation phenotype are defective in acid
      stimulated Ca2+ influx, but can be induced to deflagellate by treatment with
      nonionic detergent and Ca2+. Genetic analyses show that the five new Adf
      mutations, as well as the previously identified adf1 mutation, are alleles of the
      ADF1 gene. Mutants in the second phenotypic class, the Fa mutants, fail to
      deflagellate in response to any known chemical stimulus and are defective in Ca2+
      activated microtubule severing. Genetic analysis of these eight new Fa strains
      demonstrated that they define two complementation groups, and one of these
      contains the previously identified fa1 mutation. Diploid analysis showed that
      five alleles map to the FA1 gene, whereas four alleles define a novel gene that
      we have named FA2. The isolation of multiple mutant alleles of each gene,
      generated by either ultraviolet irradiation or insertional mutagenesis, indicates
      that ADF1, FA1, and FA2 may be the only genes that can be identified in a loss-of
      function screen. These alleles should provide a better understanding of the
      regulation of microtubule severing by Ca2+.

PMID- 9611204
TI  - An intragenic suppressor of cold sensitivity identifies potentially interacting
      bases in the peptidyl transferase center of Tetrahymena rRNA.
AB  - Peptidyl transfer of a growing peptide on a ribosome-bound transfer RNA (tRNA) to
      an incoming amino acyl tRNA is the central step in translation, and it may be
      catalyzed primarily by the large subunit (LSU) ribosomal RNA (rRNA). Genetic and
      biochemical evidence suggests that the central loop of domain V of the LSU rRNA
      plays a direct role in peptidyl transfer. It was previously found that a single
      base change at a universally conserved site in this region of the Tetrahymena
      thermophila LSU rRNA confers anisomycin resistance (an-r) as well as extremely
      slow growth, cold sensitivity, and aberrant cell morphology. Because anisomycin
      specifically inhibits peptidyl transfer, possibly by interfering with tRNA
      binding, it is likely that this mutant rRNA is defective in efficiently
      completing one of these steps. In the present study, we have isolated an
      intragenic suppressor mutation located only three bases away from the original
      mutation that partially reverses the slow growth and cold-sensitive phenotypes.
      These data imply that the functional interaction of these two bases is necessary
      for normal rRNA function, perhaps for peptidyl transfer or tRNA binding. These
      data provide the first demonstration of a functional interaction between bases
      within this rRNA region.

PMID- 9611205
TI  - The cloning by complementation of the pawn-A gene in Paramecium.
AB  - The genetic dissection of a simple avoidance reaction behavior in Paramecium
      tetraurelia has shown that ion channels are a critical molecular element in
      signal transduction. Pawn mutants, for example, were originally selected for
      their inability to swim backward, a trait that has since been shown to result
      from the loss of a voltage-dependent calcium current. The several genes defined
      by this phenotype were anticipated to be difficult to clone since the 800-ploid
      somatic macronucleus of P. tetraurelia is a formidable obstacle to cloning by
      complementation. Nonetheless, when the macronucleus of a pawn mutant (pwA/pwA)
      was injected with total wild-type DNA or a fractional library of DNA, its clonal
      descendants all responded to stimuli like the wild type. By sorting a fractional
      library, we cloned and sequenced a 2.3-kb fragment that restores the Ca2+ current
      and excitability missing in pawn-A. Data from RNase protection assays, followed
      by the sequencing of mutant alleles and cDNA clones, established an open reading
      frame. The conceptually translated product suggests a novel protein that may be
      glycophosphatidylinositol anchored. We also discuss the general usefulness of
      this method in cloning other unknown DNA sequences from Paramecium that are
      functionally responsible for various mutant phenotypes.

PMID- 9611206
TI  - Rate variation of DNA sequence evolution in the Drosophila lineages.
AB  - Rate constancy of DNA sequence evolution was examined for three species of
      Drosophila, using two samples: the published sequences of eight genes from
      regions of the normal recombination rates and new data of the four AS-C (ac, sc,
      l'sc and ase) and ci genes. The AS-C and ci genes were chosen because these genes
      are located in the regions of very reduced recombination in Drosophila
      melanogaster and their locations remain unchanged throughout the entire lineages
      involved, yielding less effect of ancestral polymorphism in the study of rate
      constancy. The synonymous substitution pattern of the three lineages was found to
      be erratic in both samples. The dispersion index for replacement substitution was
      relatively high for the per, G6pd and ac genes. A significant heterogeneity was
      found in the number of synonymous substitutions in the three lineages between the
      two samples of genes with different recombination rates. This is partly due to a
      lack of the lineage effect in the D. melanogaster and Drosophila simulans
      lineages in the AS-C and ci genes in contrast to Akashi's observation of genes in
      regions of normal recombination. The higher codon bias in Drosophila yakuba as
      compared with D. melanogaster and D. simulans was observed in the four AS-C
      genes, which suggests change(s) in action of natural selection involved in codon
      usage on these genes. Fluctuating selection intensity may also be responsible for
      the observed locus-lineage interaction effects in synonymous substitution.

PMID- 9611207
TI  - Allele-specific population structure of Drosophila melanogaster alcohol
      dehydrogenase at the molecular level.
AB  - The history of the Drosophila melanogaster alcohol dehydrogenase (ADH) Fast/Slow
      polymorphism was studied by recording molecular variation and inversion
      polymorphism in 233 chromosomes from European and African populations. Silent
      molecular variation in the Slow allele was very different between standard
      chromosomes and chromosomes bearing the In(2L)t inversion. Within populations,
      inverted Slow haplotypes were more variable than standard Slow haplotypes.
      Between populations, geographical structure was almost nonexistent for inverted
      Slow haplotypes and highly significant for standard Slow. All Fast haplotypes
      occurred on standard chromosomes. They showed little variation within and between
      populations. They were highly significantly closer to standard Slow haplotypes
      from Europe. These results suggest that the current range of Fast and In(2L)t
      Slow haplotypes is recent and that an older genetic differentiation between
      populations was followed by allele-specific gene flow.

PMID- 9611208
TI  - Candidate quantitative trait loci and naturally occurring phenotypic variation
      for bristle number in Drosophila melanogaster: the Delta-Hairless gene region.
AB  - Delta (Dl) and Hairless (H) are two chromosome 3 candidate neurogenic loci that
      might contribute to naturally occurring quantitative variation for sensory
      bristle number. To evaluate this hypothesis, we assessed quantitative genetic
      variation in abdominal and sternopleural bristle numbers among homozygous
      isogenic third chromosomes sampled from nature and substituted into the Samarkand
      (Sam) inbred chromosome 1 and 2 background; among homozygous lines in which the
      wild-derived Dl-H gene region was introgressed into the Sam chromosome 3
      background; and among Dl-H region introgression lines as heterozygotes against
      the Sam wild-type strain and derivatives of Sam into which mutant Dl and H
      alleles had been introgressed. Variation among the Dl-H region introgression
      lines accounted for 36% (8.3%) of the total chromosome 3 among line variance in
      abdominal (sternopleural) bristle number and for 53% of the chromosome 3 sex x
      line variance in abdominal bristle number. Naturally occurring alleles in the Dl
      H region failed to complement a Dl mutant allele for female abdominal bristle
      number and sternopleural bristle number in both sexes, and an H mutant allele for
      both bristle traits in males and females. These results are consistent with the
      hypothesis that naturally occurring alleles at Dl and H contribute to
      quantitative genetic variation in sensory bristle number.

PMID- 9611209
TI  - Two sites in the Delta gene region contribute to naturally occurring variation in
      bristle number in Drosophila melanogaster.
AB  - A restriction enzyme survey of a 57-kb region including the gene Delta uncovered
      53 polymorphic molecular markers in a sample of 55 naturally occurring
      chromosomes. A permutation test, which assesses the significance of the molecular
      marker with the largest effect on bristle variation in four genetic backgrounds
      relative to permuted data-sets, found two sites that were independently
      associated with variation in bristle number. A common site in the second intron
      of Delta affected only sternopleural bristle number, and another common site in
      the fifth intron affected only abdominal bristle number in females. Under an
      additive genetic model, the polymorphism in the second intron may account for 12%
      of the total genetic variation in sternopleural bristle number due to third
      chromosomes, and the site in the fifth intron may account for 6% of the total
      variation in female abdominal bristle number due to the third chromosomes. These
      results suggest the following: (1) models that incorporate balancing selection
      are more consistent with observations than deleterious mutation-selection
      equilibrium models, (2) mapped quantitative trait loci of large effect may not
      represent a single variable site at a genetic locus, and (3) linkage
      disequilibrium can be used as a tool for understanding the molecular basis of
      quantitative variation.

PMID- 9611210
TI  - Probable mechanisms underlying interallelic complementation and temperature
      sensitivity of mutations at the shibire locus of Drosophila melanogaster.
AB  - The shibire locus of Drosophila melanogaster encodes dynamin, a GTPase required
      for the fission of endocytic vesicles from plasma membrane. Biochemical studies
      indicate that mammalian dynamin is part of a complex containing multiple dynamin
      subunits and other polypeptides. To gain insight into sequences of dynamin
      critical for its function, we have characterized in detail a collection of
      conditional and lethal shi alleles. We describe a probable null allele of shi and
      show that its properties are distinct from those of two classes of lethal alleles
      (termed I and II) that show intergroup, interallelic complementation. Sequenced
      class I alleles, which display dominant properties, carry missense mutations in
      conserved residues in the GTPase domain of dynamin. In contrast, the sequenced
      class II alleles, which appear completely recessive, carry missense mutations in
      conserved residues of a previously uncharacterized "middle domain" that lies
      adjacent to the GTPase region. These data suggest that critical interactions
      mediated by this middle domain are severely affected by the class II lethal
      mutations; thus, the mutant sequences should be very useful for confirming the in
      vivo relevance of interactions observed in vitro. Viable heteroallelic
      combinations of shi lethals show rapid and reversible temperature-sensitive
      paralytic phenotypes hitherto only described for the ts alleles of shi. When
      taken together with the molecular analysis of shi mutations, these observations
      suggest that the GTPase domain of dynamin carries an intrinsically temperature
      sensitive activity: hypomorphic mutations that reduce this activity at low
      temperatures result in conditional temperature-sensitive phenotype. These
      observations explain why screens for conditional paralytic mutants in Drosophila
      inevitably recover ts alleles of shi at high frequencies.

PMID- 9611211
TI  - Transvection in the Drosophila Abd-B domain: extensive upstream sequences are
      involved in anchoring distant cis-regulatory regions to the promoter.
AB  - The Abd-B gene, one of the three homeotic genes in the Drosophila bithorax
      complex (BX-C), is required for the proper identity of the fifth through the
      eighth abdominal segments (corresponding to parasegments 10-14) of the fruitfly.
      The morphological difference between these four segments is due to the
      differential expression of Abd-B, which is achieved by the action of the
      parasegment-specific cis-regulatory regions infra-abdominal-5 (iab-5), -6, -7 and
      -8. The dominant gain-of-function mutation Frontabdominal-7 (Fab-7) removes a
      boundary separating two of these cis-regulatory regions, iab-6 and iab-7. As a
      consequence of the Fab-7 deletion, the parasegment 12- (PS12-) specific iab-7 is
      ectopically activated in PS11. This results in the transformation of the sixth
      abdominal segment (A6) into the seventh (A7) in Fab-7 flies. Here we report that
      point mutations of the Abd-B gene in trans suppress the Fab-7 phenotype in a
      pairing-dependent manner and thus represent a type of transvection. We show that
      the observed suppression is the result of trans-regulation of the defective Abd-B
      gene by the ectopically activated iab-7. Unlike previously demonstrated cases of
      trans-regulation in the Abd-B locus, trans-suppression of Fab-7 is sensitive to
      heterozygosity for chromosomal rearrangements that disturb homologous pairing at
      the nearby Ubx locus. However, in contrast to Ubx, the transvection we observed
      in the Abd-B locus is insensitive to the allelic status of zeste. Analysis of
      different deletion alleles of Abd-B that enhance trans-regulation suggests that
      an extensive upstream region, different from the sequences required for
      transcription initiation, mediates interactions between the iab cis-regulatory
      regions and the proximal Abd-B promoter. Moreover, we find that the amount of DNA
      deleted in the upstream region is roughly proportional to the strength of trans
      interaction, suggesting that this region consists of numerous discrete elements
      that cooperate in tethering the iab regulatory domains to Abd-B. Possible
      implications of the tethering complex for the regulation of Abd-B are discussed.
      In addition, we present evidence that the tenacity of trans-interactions in the
      Abd-B gene may vary, depending upon the tissue and stage of development.

PMID- 9611212
TI  - quemao, a Drosophila bristle locus, encodes geranylgeranyl pyrophosphate
      synthase.
AB  - The quemao (qm) locus of Drosophila melanogaster is characterized by a P-element
      associated mutant lacking most of the large bristles on the thorax and by several
      EMS-induced recessive lethals. quemao was cloned using a transposon tagging
      strategy. P-element-mediated transformation demonstrated that the cloned qm DNA
      sequence (from the 65F cytological region) rescues the mutant phenotype. A 2.3-kb
      qm transcript was identified by Northern blot analysis by sequencing of the
      isolated qm cDNA clones and by 5' rapid amplification cDNA end (RACE). The
      predicted amino acid sequence (338 residues) of the coding region of the qm
      transcript shares 42, 31, 13, 20, and 12% identical amino acid sequences with the
      geranylgeranyl pyrophosphate synthase (GGPPS) of fungi, yeast, plants,
      archaebacteria, and eubacteria, respectively. It also contains five highly
      conserved domains common among all known isoprenyl pyrophosphate synthases. The P
      element associated with the original qm mutant is inserted in the 5' untranslated
      region of the transcript. An EMS-induced qm nonsense mutation at the 12th codon
      leads to recessive lethality at the first larval instar, indicating the essential
      role of qm in the isoprenoid biosynthesis of insects.

PMID- 9611213
TI  - Possible assortment of a1 and a2 region gene segments in human MHC class I
      molecules.
AB  - Using pair-wise comparison of aligned nucleotide sequences of distinct and
      complete human MHC class I molecules, we have constructed triangular tables to
      study the similarities and differences of various a1 (exon 2) and a2 (exon 3)
      region sequences. There are two HLA-A (A*6901 and A*6601) and 13 HLA-B (B*4201,
      B*8101, B*4102, B*4801, B*4007, B*4001, B*4802, Dw53, B*4406, B*4402, B*3901,
      B*1514 and B*3702) sequences that have identical a1 sequences with other known
      MHC class I molecules, while their a2 sequences are the same as those of
      different ones. Of these 15, A*6901, B*4001 and B*4802 have previously been
      suggested as the results of recombination between A*6801 and A*0201, B*4101 and
      B*8101, and B*4801 and B*3501, respectively. However, many other sequences can
      also be used to generate them by recombination. Furthermore, their reciprocal
      products have never been identified. Thus, gene conversion has subsequently been
      suggested as an alternative. Another possible genetic mechanism for generating
      these nucleotide sequence similarities can be assortment, or that some gene
      segments can be duplicated or multiplicated to be used in different human MHC
      class I molecules. Interestingly, this genetic mechanism is probably absent for
      the generation of different mouse MHC class I molecules.

PMID- 9611214
TI  - Multiple marker mapping of quantitative trait loci in a cross between outbred
      wild boar and large white pigs.
AB  - A quantitative trait locus (QTL) analysis of growth and fatness data from a three
      generation pig experiment is presented. The population of 199 F2 animals was
      derived from a cross between wild boar and Large White pigs. Animals were typed
      for 240 markers spanning 23 Morgans of 18 autosomes and the X chromosome. A
      series of analyses are presented within a least squares framework. First, these
      identify chromosomes containing loci controlling trait variation and subsequently
      attempt to map QTLs to locations within chromosomes. This population gives
      evidence for a large QTL affecting back fat and another for abdominal fat
      segregating on chromosome 4. The best locations for these QTLs are within 4 cM of
      each other and, hence, this is likely to be a single QTL affecting both traits.
      The allele inherited from the wild boar causes an increase in fat deposition. A
      QTL for intestinal length was also located in the same region on chromosome 4 and
      could be the same QTL with pleiotropic effects. Significant effects, owing to
      multiple QTLs, for intestinal length were identified on chromosomes 3 and 5. A
      single QTL affecting growth rate to 30 kg was located on chromosome 13 such that
      the Large White allele increased early growth rate, another QTL on chromosome 10
      affected growth rate from 30 to 70 kg and another on chromosome 4 affected growth
      rate to 70 kg.

PMID- 9611215
TI  - Gene silencing by DNA methylation and dual inheritance in Chinese hamster ovary
      cells.
AB  - Chinese hamster ovary (CHO) cells strain D422, which has one copy of the adenine
      phosphoribosyl transferase (APRT) gene, were permeabilized by electroporation and
      treated with 5-methyl deoxycytidine triphosphate. Cells with a silenced APRT gene
      were selected on 2, 6-diaminopurine. Colonies were isolated and shown to be
      reactivated to APRT+ by 5-aza-cytidine and by selection in medium containing
      adenine, aminopterin and thymidine. Genomic DNA was prepared from eight isolates
      of independent origin and subjected to bisulphite treatment. This deaminates
      cytosine to uracil in single-stranded DNA but does not deaminate 5-methyl
      cytosine. PCR, cloning and sequencing revealed the methylation pattern of CpG
      doublets in the promoter region of the APRT- gene, whereas the active APRT gene
      had nonmethylated DNA. CHO strain K1, which has two copies of the APRT+ gene,
      could also be silenced by the same procedure but at a lower frequency. The
      availability of the 5-methyl dCTP-induced silencing, 5-aza-CR and a standard
      mutagen, ethyl methane sulphonate, makes it possible to follow concomitantly the
      inheritance of active, mutant or silenced gene copies. This analysis demonstrates
      "dual inheritance" at the APRT locus in CHO cells.

PMID- 9611216
TI  - Sequence-tagged-site (STS) markers of arbitrary genes: development,
      characterization and analysis of linkage in black spruce.
AB  - Sequence-tagged-site (STS) markers of arbitrary genes were investigated in black
      spruce [Picea mariana (Mill.) B.S.P.]. Thirty-nine pairs of PCR primers were used
      to screen diverse panels of haploid and diploid DNAs for variation that could be
      detected by standard agarose gel electrophoresis without further manipulation of
      amplification products. Codominant length polymorphisms were revealed at 15 loci.
      Three of these loci also had null amplification alleles as did 3 other loci that
      had no apparent product-length variation. Dominant length polymorphisms were
      observed at 2 other loci. Alleles of codominant markers differed in size by as
      little as 1 bp to as much as an estimated 175 bp with nearly all
      insertions/deletions found in noncoding regions. Polymorphisms at 3 loci involved
      large (33 bp to at least 114 bp) direct repeats and similar repeats were found in
      7 of 51 cDNAs sequenced. Allelic segregation was in accordance with Mendelian
      inheritance and linkage was detected for 5 of 63 pairwise combinations of loci
      tested. Codominant STS markers of 12 loci revealed an average heterozygosity of
      0.26 and an average of 2.8 alleles in a range-wide sample of 22 trees.

PMID- 9611217
TI  - Properties of maximum likelihood male fertility estimation in plant populations.
AB  - Computer simulations are used to evaluate maximum likelihood methods for
      inferring male fertility in plant populations. The maximum likelihood method can
      provide substantial power to characterize male fertilities at the population
      level. Results emphasize, however, the importance of adequate experimental design
      and evaluation of fertility estimates, as well as limitations to inference (e.g.,
      about the variance in male fertility or the correlation between fertility and
      phenotypic trait value) that can be reasonably drawn.

PMID- 9611218
TI  - Position effects of ribosomal RNA multigene loci on meiotic recombination in
      wheat.
AB  - Homeologous wheat chromosome arms that differ by the presence or absence of a Nor
      locus or greatly differ in the numbers of copies of rRNA genes per Nor locus show
      conspicuous differences in the distribution of recombination. To assess directly
      the position effects of Nor loci on recombination across chromosome arms, a
      Triticum monococcum Nor9 haplotype was substituted for Triticum aestivum Nor9
      haplotypes on two T. aestivum 1A chromosomes in the isogenic background of cv
      Chinese Spring. The numbers of rRNA genes in the 1A Nor9 haplotypes are greatly
      reduced relative to the T. monococcum haplotype. The substitution resulted in
      reduced recombination rate in the vicinity of the Nor9 locus. An intra-arm
      compensatory increase was observed in the proximal region of the arm so that the
      genetic length of the chromosome arm was unchanged. These findings suggest that
      Nor loci suppress recombination in their vicinity and change recombination
      patterns in Nor-bearing chromosome arms.

PMID- 9611219
TI  - Gametocidal genes induce chromosome breakage in the interphase prior to the first
      mitotic cell division of the male gametophyte in wheat.
AB  - Male gametogenesis was cytologically analyzed in wheat lines homozygous or
      hemizygous for gametocidal (Gc) factors with different modes of action. The first
      and second meiotic divisions in all lines were cytologically normal. The
      postmeiotic mitoses were normal in the homozygous lines; however, chromosome
      fragments and bridges were observed in the mitoses of the hemizygous lines. The
      morphology of the chromosome fragments suggests that the Gc genes induce
      chromosome breaks in the G1 phase prior to DNA synthesis of the first postmeiotic
      mitosis. The age of an anther was correlated with the frequency of aberrant
      second mitosis. Younger anthers contained a higher number of pollen undergoing
      normal second mitosis. This observation suggests that the arresting of the cell
      cycle occurs as the result of chromosome breaks during the first mitosis. Because
      chromosome bridges were more frequent than fragments in the second mitosis,
      breakage-fusion-bridge cycles possibly occurred during gametogenesis, which led
      to further chromosomal rearrangements. The Gc factors located on chromosomes 2S
      of Aegilops speltoides and 4Ssh of Ae. sharonensis induce severe chromosome
      breakage in pollen lacking them. However, the Gc factor on telosome 2CcL of Ae.
      cylindrica only induced chromosome breaks at a low frequency. The observed
      partial fertility of Gc lines is presumably due to cell cycle arrest and the
      competition among gametes with and without chromosome breakage.

PMID- 9611220
TI  - The maize regulatory gene B-Peru contains a DNA rearrangement that specifies
      tissue-specific expression through both positive and negative promoter elements.
AB  - The B-Peru allele of the maize b regulatory gene is unusual relative to most b
      alleles in that it is expressed in the aleurone layer of the seed. It is also
      expressed in a subset of plant vegetative tissues. Transgenic maize plants
      containing the B-Peru gene with the first 710 bases of upstream sequence
      conferred the same levels of aleurone expression as nontransgenic B-Peru plants,
      but no pigment was made in vegetative tissues. Transient transformation assays in
      aleurone tissue localized the aleurone-specific promoter to the first 176 bases
      of the B-Peru upstream region and identified two critically important regions
      within this fragment. Mutation of either region alone reduced expression greater
      than fivefold. Surprisingly, the double mutation actually increased expression to
      twice the native promoter level. Our results suggest that these two critical
      sequences, which lie close together in the promoter, may form a negative
      regulatory element. Several lines of evidence suggest that the B-Peru promoter
      arose through the translocation of an existing aleurone-specific promoter to the
      b locus. Immediately upstream of the aleurone-specific promoter elements and in
      the opposite orientation to the b coding sequence is a pseudogene sequence with
      strong similarity to a known class of proteins. Our findings that novel aleurone
      specific promoter sequences of the B-Peru transcription factor are found adjacent
      to part of another gene in a small insertion are quite unexpected and have
      interesting evolutionary implications.

PMID- 9611222
TI  - One-locus two-allele models with maternal (parental) selection.
AB  - I formulate and study a series of simple one-locus two-allele models for maternal
      (parental) selection. I show that maternal (parental) selection can result in
      simultaneous stability of equilibria of different types. Thus, in the presence of
      maternal (parental) selection the outcome of population evolution can
      significantly depend on initial conditions. With maternal selection, genetic
      variability can be maintained in the population even if none of the offspring of
      heterozygous mothers survive. I demonstrate that interactions of maternal and
      paternal selection can result in stable oscillations of genotype frequencies. A
      necessary condition for cycling is strong selection.

PMID- 9611221
TI  - Combining different line crosses for mapping quantitative trait loci using the
      identical by descent-based variance component method.
AB  - Mapping quantitative trait loci (QTLs) is usually conducted with a single line
      cross. The power of such QTL mapping depends highly on the two parental lines. If
      the two lines are fixed for the same allele at a putative QTL, the QTL is
      undetectable. On the other hand, if a QTL is segregating in the line cross and is
      detected, the estimated variance of the QTL cannot be extrapolated beyond the
      statistical inference space of the two parental lines. To reduce the likelihood
      of missing a QTL and to increase the statistical inference space of the estimated
      QTL variance, we present a consensus QTL mapping strategy. We adopt the identical
      by descent (IBD)-based variance component method originally applied to human
      linkage analysis by combining multiple line crosses as independent families. We
      explore the properties of consensus QTL mapping and demonstrate the method with
      F2, backcross (BC), and full-sib (FS) families. In addition, we examine the
      effects of the QTL heritability, marker informativeness, QTL position, the number
      of families, and family size. We show that F2 families notably outperform BC and
      FS families in detecting a QTL. There is a substantial reduction in the standard
      deviation of the estimated QTL position and the separation of the QTL and
      polygenic variance. Finally, we show that the power to detect a QTL is greater
      when using a small number of large families than a large number of small
      families.

PMID- 9611223
TI  - The number of self-incompatibility alleles in a finite, subdivided population.
AB  - The actual and effective number of gametophytic self-incompatibility alleles
      maintained at mutation-drift-selection equilibrium in a finite population
      subdivided as in the island model is investigated by stochastic simulations. The
      existing theory founded by Wright predicts that for a given population size the
      number of alleles maintained increases monotonically with decreasing migration as
      is the case for neutral alleles. The simulation results here show that this is
      not true. At migration rates above Nm = 0.01-0.1, the actual and effective number
      of alleles is lower than for an undivided population with the same number of
      individuals, and, contrary to Wright's theoretical expectation, the number of
      alleles is not much higher than for an undivided population unless Nm < 0.001.
      The same pattern is observed in a model where the alleles display symmetrical
      overdominant selection. This broadens the applicability of the results to include
      proposed models for the major histocompatibility (MHC) loci. For a subdivided
      population over a large range of migration rates, it appears that the number of
      self-incompatibility alleles (or MHC-alleles) observed can provide a rough
      estimate of the total number of individuals in the population but it
      underestimates the neutral effective size of the subdivided population.

PMID- 9611225
TI  - Evolutionary conservation of histone macroH2A subtypes and domains.
AB  - Histone macroH2A is an unusual core histone that contains a large non-histone
      region, and a region that resembles a full length H2A. We examined
      theconservation of this novel structural arrangement by cloning chicken macroH2A
      cDNAs and comparing them to their rat counterparts. The amino acid sequences of
      the two known macroH2A subtypes are >95% identical between these species despite
      evolutionary separation of approximately 300 million years. The H2A region of
      macroH2A is completely conserved, and thus is even more conserved than
      conventional H2A in these species. The origin of the non-histone domain was
      examined by comparing its sequence to proteins found in bacteria and RNA viruses.
      These comparisons indicate that this domain is derived from a gene that
      originated prior to the appearance of eukaryotes, and suggest that the non
      histone region has retained the basic function of its ancestral gene.

PMID- 9611224
TI  - Cisplatin inhibits synthesis of ribosomal RNA in vivo.
AB  - Cis -diammininedichloroplatinum(II) (cisplatin or cis -DDP) is a DNA-damaging
      agent that is widely used in cancer chemotherapy. Cisplatin crosslinks DNA and
      the resulting adducts interact with proteins that contain high-mobility-group
      (HMG) domains, such as UBF(upstream binding factor). UBF is a transcription
      factor that binds to the promoter of ribosomal RNA (rRNA) genes thereby
      supporting initiation of transcription by RNA polymerase I. Here we report that
      cisplatin causes a redistribution of UBF in the nucleolus of human cells, similar
      to that observed after inhibition of rRNA synthesis. A similar redistribution was
      observed for the major components of the rRNA transcription machinery, namely
      TBP, TAFIs and RNA polymerase I. Furthermore, we provide for the first time
      direct in vivo evidence that cisplatin blocks synthesis of rRNA, while activity
      of RNA polymerase II continues to be detected throughout the nucleus. The
      clinically ineffective trans isomer (trans -DDP) does not alter the localization
      of either UBF or other components of the RNA polymerase I transcription
      machinery. These results suggest that disruption of rRNA synthesis, which is
      stimulated in proliferating cells, plays an important role in the clinical
      success of cisplatin.

PMID- 9611226
TI  - Non-homologous recombination mediated by Thermus aquaticus DNA polymerase I.
      Evidence supporting a copy choice mechanism.
AB  - RT-PCR amplification of P450 2C6 from rat liver, using primers in opposite
      orientations of exon 6, resulted in PCR products containing segments of exons
      joined at non-consensus splice sites. Moreover, many of the PCR products
      identified were composed of not only a single region containing exonic segments
      joined at non-consensus splice sites but, instead, of several repeats of the non
      canonically joined region. To investigate whether these PCR products represent
      pre-existing molecules or are generated during the amplification process, the
      liver cDNA template was replaced by a plasmid containing the P450 2C6 cDNA.
      Surprisingly, PCR products containing repeats of non-canonically joined exonic
      segments were again revealed. In some cases the position of this non-canonical
      joining was a sequence of one or two identical nucleotides; however, there were
      also a number of products lacking any nucleotide identity at the position of
      joining. DNA nicking and/or DNA damage is thought to favour recombination during
      PCR, probably by misalignment of incomplete DNA strands; however, the presence of
      multiple repeats of the recombined region in the PCR products identified suggests
      a certain repetitiveness of the underlying mechanism. It is therefore proposed
      that these products result from a template switching event that occurs several
      times during a single polymerization step, following a rolling circle model of
      DNA synthesis.

PMID- 9611227
TI  - Stochastic, stage-specific mechanisms account for the variegation of a human
      globin transgene.
AB  - The random insertion of transgenes into the genomic DNA of mice usually leads to
      widely variable levels of expression in individual founder lines. To study the
      mechanisms that cause variegation, we designed a transgene that we expected to
      variegate, which consisted of a beta-globin locus control region 5' HS-2 linked
      in tandem to a tagged human beta-globin gene (into which a Lac-Z cassette had
      been inserted). All tested founder lines exhibited red blood cell-specific
      expression, but levels of expression varied >1000-fold from the lowest to the
      highest expressing line. Most of the variation in levels of expression appeared
      to reflect differences in the percentage of cells in the peripheral blood that
      expressed the transgene, which ranged from 0.3% in the lowest expressing line to
      88% in the highest; the level of transgene expression per cell varied no more
      than 10-fold from the lowest to the highest expressing line. These differences in
      expression levels could not be explained by the location of transgene
      integration, by an effect of beta-galactosidase on red blood cell survival, by
      the half life of the beta-galactosidase enzyme or by the age of the animals. The
      progeny of all early erythroid progenitors (BFU-E colony-forming cells) exhibited
      the same propensity to variegate in methylcellulose-based cultures, suggesting
      that the decision to variegate occurs after the BFU-E stage of erythroid
      differentiation. Collectively, these data suggest that variegation in levels of
      transgene expression are due to local, integration site-dependent phenomena that
      alter the probability that a transgene will be expressed in an appropriate cell;
      however, these local effects have a minimal impact on the transgene's activity in
      the cells that initiate transcription.

PMID- 9611228
TI  - Overexpression of Rad51 protein stimulates homologous recombination and increases
      resistance of mammalian cells to ionizing radiation.
AB  - Rad51 proteins share both structural and functional homologies with the bacterial
      recombinase RecA. The human Rad51 (HsRad51) is able to catalyse strand exchange
      between homologous DNA molecules in vitro . However the biological functions of
      Rad51 in mammals are largely unknown. In order to address this question, we have
      cloned hamster Rad51 cDNA and overexpressed the corresponding protein in CHO
      cells. We found that 2-3-fold overexpression of the protein stimulated the
      homologous recombination between integrated genes by 20-fold indicating that
      Rad51 is a functional and key enzyme of an intrachromosomal recombination
      pathway. Cells overexpressing Rad51 were resistant to ionizing radiation when
      irradiated in late S/G2phase of the cell cycle. This suggests that Rad51
      participate in the repair of double-strand breaks most likely by homologous
      recombination involving sister chromatids formed after the S phase.

PMID- 9611229
TI  - Transcription of INO2 and INO4 is regulated by the state of protein N
      myristoylation in Saccharomyces cerevisiae.
AB  - Inositol regulates transcription of Saccharomyces cerevisiae genes required for
      de novo synthesis of acylCoAs and phospholipids. Removal of inositol results in
      transcriptional activation by heterodimeric complexes of two bHLH proteins, Ino2p
      and Ino4p. In the presence of inositol, transcription is repressed by Opi1p.
      MyristoylCoA:protein N-myristoyltransferase (Nmt1p) is an essential enzyme whose
      activity is influenced by cellular myristoylCoA pool size and availability.
      nmt451Dp contains a Gly451-->Asp substitution that produces temperature-dependent
      reductions in affinity for myristoylCoA and associated reductions in acylation of
      cellular N-myristoylproteins. The conditional lethality produced by nmt1-451D is
      rescued at temperatures up to 33 degreesC by withdrawal of inositol. We tested
      the hypothesis that N-myristoylproteins function to regulate INO2, INO4 and/or
      OPI1 transcription, thereby affecting the expression of inositol-sensitive genes
      that influence myristoylCoA metabolism. The effect of nmt1-451D on INO2 , INO4
      and OPI1 promoter activities was examined by introducing episomes, containing
      their 5' non-transcribed domains linked to reporters, into isogenic NMT1 and nmt1
      451D cells. The activity of INO2 is significantly higher, INO4 significantly
      lower and OPI1 unaffected in nmt1-451D cells, both in the presence and absence of
      inositol. These changes are associated with a net increase in expression of some
      inositol target genes, including FAS1 . FAS1 encodes one of the subunits of the
      fatty acid synthase complex that catalyzes de novo acylCoA (including
      myristoylCoA) biosynthesis. Augmented expression of FAS1 overcomes the kinetic
      defects in nmt451Dp. FAS1 expression is Ino2p-dependent in NMT1 cells at 24-33
      degreesC. In contrast, FAS1 expression becomes Ino2p-independent in nmt1-451D
      cells at temperatures where efficient acylation of cellular N-myristoylproteins
      is jeopardized. The ability to maintain expression of FAS1 in nmt1-451Dino2 Delta
      cells suggests the existence of another transcription factor, or factors, whose
      expression/activity is inversely related to overall levels of cellular protein N
      myristoy-lation. This factor is not functionally identical to Ino2p since other
      inositol-responsive genes (e.g. CHO1 ) maintain INO2 -dependent expression in
      nmt1-451D cells.

PMID- 9611230
TI  - Visualisation of extensive water ribbons and networks in a DNA minor-groove drug
      complex.
AB  - The crystal structure is reported of a complex between an ethyl derivative of the
      minor-groove drug furamidine and the dodecanucleotide duplex d(CGCGAATTCGCG)2,
      which has been refined to 1.85 A resolution and an R factor of 16.6% for data
      collected at -173 degreesC. An exceptionally large number (220) of water
      molecules have been located. The majority of these occur in the first
      coordination shell of solvation. There are extensive networks of connected
      waters, both in the major and minor grooves. In particular, there are 21 water
      molecules associated with the minor-groove drug, via hydrogen bonds from the four
      charged nitrogen atoms. One cluster of four waters is situated in the groove
      itself; the majority are on the outer edge of the groove, and serve to bridge
      between the outward-directed drug nitrogen atoms and backbone phosphate oxygen
      atoms. These bridges are both intra- and inter-strand, with the net effect that
      the outer edge of the drug molecule is covered by ribbons of water molecules.

PMID- 9611231
TI  - Characterization of Werner syndrome protein DNA helicase activity:
      directionality, substrate dependence and stimulation by replication protein A.
AB  - Werner syndrome is an inherited disease characterized by premature aging, genetic
      instability and a high incidence of cancer. The wild type Werner syndrome protein
      (WRN) has been demonstrated to exhibit DNA helicase activity in vitro. Here we
      report further biochemical characterization of the WRN helicase. The enzyme
      unwinds double-stranded DNA, translocating 3'-->5' on the enzyme-bound strand.
      Hydrolysis of dATP or ATP, and to a lesser extent hydrolysis of dCTP or CTP,
      supports WRN-catalyzed strand-displacement. K m values for ATP and dATP are 51
      and 119 microM, respectively, and 2.1 and 3.9 mM for CTP and dCTP, respectively.
      Strand-displacement activity of WRN is stimulated by single-stranded DNA-binding
      proteins (SSBs). Among the SSBs from Escherichia coli, bacteriophage T4 and
      human, stimulation by human SSB (human replication protein A, hRPA) is the most
      extensive and occurs with a stoichiometry which suggests direct interaction with
      WRN. A deficit in the interaction of WRN with hRPA may be associated with
      deletion mutations that occur at elevated frequency in Werner syndrome cells.

PMID- 9611232
TI  - TAR-RNA binding by HIV-1 Tat protein is selectively inhibited by its L
      enantiomer.
AB  - An oligoribonucleotide, corresponding to the Tat-interactive top half of the HIV
      1 TAR RNA stem-loop, was synthesized in both the natural D- and the enantiomeric
      L-configurations. The affinity of Tat for the two RNAs, assessed by competition
      binding experiments, was found to be identical and is reduced 10-fold for both,
      upon replacement of the critical bulge residue U23 with cytidine. It is suggested
      that this interaction of the flexible Tat protein depends strongly upon the
      tertiary structure of a binding pocket within TAR, but not upon its handedness,
      and may be described by a 'hand-in-mitten' model.

PMID- 9611233
TI  - Auxiliary downstream elements are required for efficient polyadenylation of
      mammalian pre-mRNAs.
AB  - We have previously identified a G-rich sequence (GRS) as an auxiliary downstream
      element (AUX DSE) which influences the processing efficiency of the SV40 late
      polyadenylation signal. We have now determined that sequences downstream of the
      core U-rich element (URE) form a fundamental part of mammalian polyadenylation
      signals. These novel AUX DSEs all influenced the efficiency of 3'-end processing
      in vitro by stabilizing the assembly of CstF on the core downstream URE. Three
      possible mechanisms by which AUX DSEs mediate efficient in vitro 3'-end
      processing have been explored. First, AUX DSEs can promote processing efficiency
      by maintaining the core elements in an unstructured domain which allows the
      general polyadenylation factors to efficiently assemble on the RNA substrate.
      Second, AUX DSEs can enhance processing by forming a stable structure which helps
      focus binding of CstF to the core downstream URE. Finally, the GRS element, but
      not the binding site for the bacteriophage R17 coat protein, can substitute for
      the auxiliary downstream region of the adenovirus L3 polyadenylation signal. This
      suggests that AUX DSE binding proteins may play an active role in stimulating 3'
      end processing by stabilizing the association of CstF with the RNA substrate. AUX
      DSEs, therefore, serve as a integral part of the polyadenylation signal and can
      affect signal strength and possibly regulation.

PMID- 9611234
TI  - The corepressor N-CoR and its variants RIP13a and RIP13Delta1 directly interact
      with the basal transcription factors TFIIB, TAFII32 and TAFII70.
AB  - Repression of transcription by the classical nuclear receptors (e.g. TR, RAR),
      the orphan nuclear receptors (e.g. Rev-erbAalpha/beta), Mxi-1 and Mad bHLH-zip
      proteins and the oncoproteins PLZF and LAZ3/BCL6 is mediated by the corepressors
      N-CoR and SMRT. The interaction of the corepressors with the components involved
      in chromatin remodelling, such as the recruiting proteins Sin3A/B and the histone
      deacteylases HDAc-1 and RPD3, has been analysed in detail. The N-CoR/Sin3/HDAc
      complexes have a key role in the regulation of cellular proliferation and
      differentiation. However, the interaction of these corepressors with the basal
      transcriptional machinery has remained obscure. In this study we demonstrated
      that the N-terminalrepression domains and the receptor interactiondomains (RID)
      of N-CoR and its splice variants, RIP13a and RIP13Delta1, directly interact with
      TAFII32 in vivo and in vitro . We show that interaction domain II within the N
      CoR and RIP13a RID is required for the interaction with TAFII32. We also observed
      that N-CoR directly interacts with each of the basal factors, TFIIB and TAFII70,
      and can simultaneously interact with all three basal factors in a non-competitive
      manner. Furthermore, we provide evidence that suggests the RVR/Rev-erbbeta
      corepressor complex also interacts with the general transcriptional machinery,
      and that the physicalassociation of TFIIB with N-CoR also occurs in the presence
      of Sin3B and HDAc-1. Interestingly, we observed that N-CoR expression ablated the
      functional interaction between TFIIB and TAFII32 that is critical to the
      initiation of transcription. In conclusion, this study demonstrates that the N
      terminal repressor region and the C-terminal RIDs are part of the corepressor
      contact interface that mediates the interaction with the general transcription
      factors, and demonstrates that TAFs can also directly interact with corepressors
      to mediate signals from repressors to the basal machinery. We also suggest that N
      CoR interacts with the central components of the transcriptional initiation
      process (TFIIB, TAFs) and locks them into a non-functional complex or
      conformation that is not conducive to transcription.

PMID- 9611235
TI  - In vitro and in vivo reconstitution and stability of vertebrate chromosome ends.
AB  - Telomeres are essential repetitive sequences at the ends of chromosomes that
      prevent chromosome fusion and degradation. We have successfully recapitulated
      these two protective functions in vivo and in vitro by incubating blunt-end DNA
      constructs having vertebrate telomeric ends in Xenopus eggs and egg extracts.
      Constructs with telomeric ends are stable as linear molecules; constructs with
      non-telomeric ends undergo intramolecular fusion. In extracts, 99.8% of the
      telomeric constructs from 78 to 700 bp in length are assembled into 'model
      telomeres' in <5 min and have an extra-polated half-life of >3.5 years. Non
      telomeric constructs circularize with first order kinetics and a half-life of 4
      h. In living eggs the telomeric constructs are protected from fusion and
      degradation. The stability of the telomeric constructs is not due to covalent
      processing. Extract can protect approximately 100 pM telomeric ends (equivalent
      to 1.7 x 10(7) ends/egg) even in the presence of a 20-fold excess of double
      stranded telomeric DNA, suggesting that protection requires end-specific factors.
      Constructs with (TTGGGG) n repeats are unstable, suggesting that short tracts of
      this and other telomere-like sequences found within human telomeres could lead to
      genome instability if exposed by partial telomere erosion during aging.

PMID- 9611236
TI  - Mitochondrial targeting of human DNA glycosylases for repair of oxidative DNA
      damage.
AB  - Oxidative damage to mitochondrial DNA has been implicated in human degenerative
      diseases and aging. Although removal of oxidative lesions from mitochondrial DNA
      occurs, the responsible DNA repair enzymes are poorly understood. By expressing
      the epitope-tagged proteins in COS-7 cells, we examined subcellular localizations
      of gene products of human DNA glycosylases: hOGG1, hMYH and hNTH1. A gene
      encoding for hOGG1 which excises 7,8-dihydro-8-oxoguanine (8-oxoG) from DNA
      generates four isoforms by alternative splicing (types 1a, 1b, 1c and 2). Three
      tagged isoforms (types 1b, 1c and 2) were localized in the mitochondria. Type 1a
      protein, which exclusively contains a putative nuclear localization signal, was
      sorted to the nucleus and lesser amount to the mitochondria. hMYH, a human
      homolog gene product of Escherichia coli mutY was mainly transported into the
      mitochondria. hNTH1 protein excising several pyrimidine lesions was transported
      into both the nucleus and mitochondria. In contrast to the three DNA
      glycosylases, translocation of the human major AP endonuclease (hAPE) into the
      mitochondria was hardly observed in COS-7 cells. These results suggest that the
      previously observed removal of oxidative base lesions in mitochondrial DNA is
      initiated by the above DNA glycosylases.

PMID- 9611237
TI  - Chromatin remodeling of the interleukin-2 gene: distinct alterations in the
      proximal versus distal enhancer regions.
AB  - Known transcription factor-DNA interactions in the minimal enhancer of the murine
      interleukin-2 gene (IL-2) do not easily explain the T cell specificity of IL-2
      regulation. To seek additional determinants of cell type specificity, in vivo
      methodologies were employed to examine chromatin structure 5' and 3' of the 300
      bp IL-2 proximal promoter/enhancer region. Restriction enzyme accessibility
      revealed that until stimulation the IL-2 proximal promoter/enhancer exists in a
      closed conformation in resting T and non-T cells alike. Within this promoter
      region, DMS and DNase I genomic footprinting also showed no tissue-specific
      differences prior to stimulation. However, DNase I footprinting of the distal 
      600 to -300 bp region revealed multiple tissue-specific and stimulation
      independent DNase I hypersensitive sites. Gel shift assays detected T cell
      specific complexes binding within this region, which include TCF/LEF or HMG
      family and probable Oct family components. Upon stimulation, new DNase I
      hypersensitive sites appeared in both the proximal and distal enhancer regions,
      implying that there may be a functional interaction between these two domains.
      These studies indicate that a region outside the established IL-2 minimal
      enhancer may serve as a stable nucleation site for tissue-specific factors and as
      a potential initiation site for activation-dependent chromatin remodeling.

PMID- 9611238
TI  - Induction of XIST expression from the human active X chromosome in mouse/human
      somatic cell hybrids by DNA demethylation.
AB  - X chromosome inactivation occurs early in mammalian development to
      transcriptionally silence one of the pair of X chromosomes in females. The XIST
      RNA, a large untranslated RNA that is expressed solely from the inactive X
      chromosome, is implicated in the process of inactivation. As previous studies
      have shown that the XIST gene is methylated on the active X chromosome, we have
      treated a mouse/human somatic cell hybrid retaining an active human X chromosome
      with demethylating agents to determine whether expression of the human XIST gene
      could be induced. Stable expression of XIST was observed after several rounds of
      demethylation and stability of XIST expression correlated with the loss of
      methylation at the three sites analysed. We conclude that methylation is
      sufficient to inhibit expression of the XIST gene in somatic cell hybrids. No
      loss of expression was detected for eight other X-linked genes from the active X
      chromosome that was expressing XIST , suggesting that additional developmental or
      species-specific factors are required for the inactivation process.

PMID- 9611239
TI  - Combining diverse evidence for gene recognition in completely sequenced bacterial
      genomes.
AB  - Analysis of a newly sequenced bacterial genome starts with identification of
      protein-coding genes. Functional assignment of proteins requires the exact
      knowledge of protein N-termini. We present a new program ORPHEUS that identifies
      candidate genes and accurately predicts gene starts. The analysis starts with a
      database similarity search and identification of reliable gene fragments. The
      latter are used to derive statistical characteristics of protein-coding regions
      and ribosome-binding sites and to predict the complete set of genes in the
      analyzed genome. In a test on Bacillus subtilis and Escherichia coli genomes, the
      program correctly identified 93.3% (resp. 96.3%) of experimentally annotated
      genes longer than 100 codons described in the PIR-International database, and for
      these genes 96.3% (83.9%) of starts were predicted exactly. Furthermore, 98.9%
      (99.1%) of genes longer than 100 codons annotated in GenBank were found, and
      92.9% (75.7%) of predicted starts coincided with the feature table description.
      Finally, for the complete gene complements of B.subtilis and E.coli , including
      genes shorter than 100 codons, gene prediction accuracy was 88.9 and 87.1%,
      respectively, with 94.2 and 76.7% starts coinciding with the existing annotation.

PMID- 9611241
TI  - Interaction between the N-terminal domain of human DNA topoisomerase I and the
      arginine-serine domain of its substrate determines phosphorylation of SF2/ASF
      splicing factor.
AB  - Human DNA topoisomerase I, known for its DNA-relaxing activity, is possibly one
      of the kinases phosphorylating members of the SR protein family of splicing
      factors, in vivo. Little is known about the mechanism of action of this novel
      kinase. Using the prototypical SR protein SF2/ASF (SRp30a) as model substrate, we
      demonstrate that serine residues phosphorylated by topo I/kinase exclusively
      located within the most extended arginine-serine repeats of the SF2/ASF RS
      domain. Unlike other kinases such as cdc2 and SRPK1, which also phosphorylated
      serines at the RS domain, topo I/kinase required several SR dipeptide repeats.
      These repeats possibly contribute to a versatile structure in the RS domain
      thereby facilitating phosphorylation. Furthermore, far-western, fluorescence
      spectroscopy and kinase assays using the SF2/ASF mutants, demonstrated that
      kinase activity and binding were tightly coupled. Since the deletion of N
      terminal 174 amino acids of Topo I destroys SF2/ASF binding and kinase activity
      but not ATP binding, we conclude that at least two distinct domains of Topo I are
      necessary for kinase activity: one in the C-terminal region contributing to the
      ATP binding site and the other one in the N-terminal region that allows binding
      of SF2/ASF.

PMID- 9611242
TI  - The C-terminal domain but not the tyrosine 723 of human DNA topoisomerase I
      active site contributes to kinase activity.
AB  - Human DNA topoisomerase I not only has DNA relaxing activity, but also splicing
      factors phosphorylating activity. Topo I shows strong preference for ATP as the
      phosphate donor. We used photoaffinity labeling with the ATP analogue [alpha-32P]
      8-azidoadenosine-5'-triphosphate combined with limited proteolysis to
      characterize Topo I domains involved in ATP binding. The majority of incorporated
      analogue was associated with two fragments derived from N-terminal and C-terminal
      regions of Topo I, respectively. However, mutational analysis showed that
      deletion of the first 138 N-terminal residues, known to be dispensable for
      topoisomerase activity, did not change the binding of ATP or the kinase activity.
      In contrast, deletion of 162 residues from the C-terminal domain was deleterious
      for ATP binding, kinase and topoisomerase activities. Furthermore, a C-terminal
      tyrosine 723 mutant lacking topoisomerase activity is still able to bind ATP and
      to phosphorylate SF2/ASF, suggesting that the two functions of Topo I can be
      separated. These findings argue in favor of the fact that Topo I is a complex
      enzyme with a number of potential intra-cellular functions.

PMID- 9611240
TI  - Cloning of Drosophila GCN5: conserved features among metazoan GCN5 family
      members.
AB  - PCAF and hGCN5 are distinct human genes that encode proteins related to the yeast
      histone acetyltransferase and transcriptional adapter GCN5. The PCAF protein
      shares extensive similarity with the 439 amino acids of yGCN5, but it has an
      approximately 350 amino acid N-terminal extension that interacts with the
      transcriptional co-activator p300/CBP. Adenoviral protein E1a can disrupt PCAF
      CBP interactions and prevent PCAF-dependent cellular differentiation. In this
      report, we describe the cloning and initial characterization of a Drosophila
      homolog of yGCN5. In addition to the homology to yGCN5, the Drosophila protein
      shares sequencesimilarity with the N-terminal portion of human PCAF that is
      involved in binding to CBP. In the course of characterizing dGCN5, we have
      discovered that hGCN5 also contains an N-terminal extension with significant
      similarity to PCAF. Interestingly, in the case of the h GCN5 gene, alternative
      splicing may regulate the production of full-length hGCN5. The presence of the N
      terminal domain in a Drosophila GCN5 homolog and both human homologs suggests
      that it was part of the ancestral form of metazoan GCN5.

PMID- 9611243
TI  - Oligonucleotide bias in Bacillus subtilis: general trends and taxonomic
      comparisons.
AB  - We present a general analysis of oligonucleotide usage in the complete genome of
      Bacillus subtilis . Several datasets were built in order to assign various
      biological contexts to the biased use of words and to reveal local asymmetries in
      word usage that may be coupled with replication, the control of gene expression
      and the restriction/modification system. This analysis was complemented by cross
      comparisons with the complete genomes of Escherichia coli , Haemophilus
      influenzae and Methanococcus jannaschii . We have observed a large number of
      biased oligonucleotides for words of size up to 8, throughout the datasets and
      species, indicating that such long strict words play an important role as
      biological signals. We speculate that some of them are involved in interactions
      with DNA and/or RNA polymerases. An extensive analysis of palindrome abundances
      and distributions provides the surprising result that prophage-like elements
      embedded in the genome exhibit a smaller avoidance of restriction sites. This may
      reinforce a recently proposed hypothesis of a selfish gene phenomena in the
      transfer of restriction/modification systems in bacteria.

PMID- 9611244
TI  - A novel palindromic triple-stranded structure formed by homopyrimidine dodecamer
      d-CTTCTCCTCTTC and homopurine hexamer d-GAAGAG.
AB  - We have carried out NMR and molecular mechanics studies on a complex formed when
      a palindromic homopyrimidine dodecamer (d-CTTCTCCTCTTC) and a homopurine hexamer
      (d-GAAGAG) are mixed in 1:1 molar ratio in aqueous solutions. Such studies
      unequivocally establish that two strands of each oligomer combine to form a
      triple-stranded DNA structure with a palindromic symmetry and with six T.A:T and
      six C+. G:C hydrogen-bonded base triads. The two purine strands are placed head
      to head, with their 3' ends facing each other in the center of the structure. One
      half of each pyrimidine strand contains protonated and the other half contains
      non-protonated cytosines. The two half segments containing protonated cytosines
      are hydrogen bonded to each of the two purine hexamers through Hoogsteen T.A and
      C+.G base pairing. The segments containing non-protonated cytosines are involved
      in Watson-Crick (A:T and G:C) base pairing. This leads to a palindromic triplex
      with a C2-dyad symmetry with respect to the center of the structure. The complex
      is less stable at neutral pH, but the cytosines involved in Hoogsteen base
      pairing remain protonated even under these conditions. Molecular mechanics
      calculations using NMR constraints have provided a detailed three-dimensional
      structure of the complex. The entire stretches of purine, and the pyrimidine
      nucleotides have a conformation close to B-DNA.

PMID- 9611245
TI  - Down regulation of extramacrochaetae mRNA by a Drosophila neural RNA binding
      protein Rbp9 which is homologous to human Hu proteins.
AB  - Rbp9 is an RNA binding protein expressed mainly in the central nervous system of
      adult Drosophilamelanogaster. Rbp9 shares a high degree of sequence similarity
      with human neural proteins referred to as Hu antigens. Hu antigens bind to U-rich
      mRNA destabilizing elements with a high affinity and, thus, have been implicated
      as regulators of mRNA stability. Using in vitro RNA binding assays, we found that
      Rbp9 binds strongly to poly U sequences. We then employed a Selex system to
      identify a consensus Rbp9 binding site (UUUXUUUU). Information obtained from the
      Selex results allowed the detection of two repeats of the Rbp9 consensus binding
      sequence in the 3' untranslated region of extramacrochaetae mRNA. UV crosslinking
      experiments demonstrated that Rbp9 interactsspecifically with emc mRNA. The
      requirement of Rbp9 protein in the down regulation of emc mRNA was confirmed by
      northern (RNA) analysis, which revealed that the level of emc mRNA increased 10
      fold in rbp9 mutant flies. Taken together with the in vitro RNA binding results,
      the genetic evidence obtained strongly supports the hypothesis that Rbp9
      functions as a regulator of RNA stability.

PMID- 9611246
TI  - Non-enzymatic, template-directed ligation of 2'-5' oligoribonucleotides. Joining
      of a template and a ligator strand.
AB  - Decauridylate containing exclusively a 2'-5' phospho-diester bond ([2'-5']U10)
      served as a template for the synthesis of oligoadenylates [oligo(A)s] from the 5'
      phosphorimidazolide of 2'-5' diadenylate (ImpA-2'p5'A). Joining of [2'-5']U10and
      ImpA2'p5'A also took place in substantial amounts to yield long-chain
      oligoribonucleotides in the template-directed reaction. An unusual CD spectrum
      ascribed to helix formation between [2'-5']U10and [2'-5'](pA)2was observed under
      the same conditions as that of the template-directed reaction. The 3'-5' linked
      decauridylate ([3'-5']U10) also promoted the template-directed synthesis of
      oligo(A)s from ImpA2'p5'A, but more slowly compared with [2'-5']U10. The results
      indicate that short-chain RNA oligomers with a 2'-5' phosphodiester bond could
      lead to longer oligoribonucleotides by template-directed chain elongation.

PMID- 9611247
TI  - Binding of the modified daunorubicin WP401 adjacent to a T-G base pair induces
      the reverse Watson-Crick conformation: crystal structures of the WP401-TGGCCG and
      WP401-CGG[br5C]CG complexes.
AB  - 2'-Bromo-4'-epi-daunorubicin (alpha-manno configuration, denoted WP401) is a new
      anthracycline drug that exhibits promising activity toward multidrug-resistant
      cancer cells. We carried out X-ray diffraction analyses of the complexes formed
      in the presence of formaldehyde between WP401 and two DNA hexamers, TGGCCG and
      CGG[br5C]CG. The two complexes crystallized in different crystal lattices with
      respective crystal data of space group P4322, a = b = 37.20 A, c = 70.53 A and
      space group P43212, a = b = 37.23 A, c = 61. 96 A. These new crystal forms are
      different from the P41212 form of other daunorubicin/doxorubicin complexes
      studied previously. The refined crystal structures at approximately 2.0 A
      resolution revealed that the entire 2:1 drug-DNA complex is in the asymmetrical
      unit. Two WP401 drug molecules bind to the duplex, with the aglycones
      intercalated between the CpG or TpG steps and their modified daunosamines in the
      minor groove. As observed earlier, in the presence of formaldehyde, WP401 more
      readily forms a covalent adduct with (C/T)GG*:CCG than with (C/T)GC:G*CG (G* is
      the crosslink site), the opposite of what is seen for daunorubicin and
      doxorubicin. Surprisingly, the two T-G mismatched base pairs in the WP401-TGGCCG
      complex adopt the reverse Watson-Crick conformation, instead of the wobble
      conformation. The unusual T-G reverse Watson-Crick conformation may be required
      in order to maintain favorable stacking interactions between the base pair and
      the aglycone of WP401. Our results show that chemical modifications like bromo or
      iodo substitution on anthracycline drugs have significant effects on their DNA
      binding properties.

PMID- 9611248
TI  - Primer design for large scale sequencing.
AB  - We have developed PRIDE, a primer design program that automatically designs
      primers in single contigs or whole sequencing projects to extend the already
      known sequence and to double strand single-stranded regions. The program is fully
      integrated into the Staden package (GAP4) and accessible with a graphical user
      interface. PRIDE uses a fuzzy logic-based system to calculate primer qualities.
      The computational performance of PRIDE is enhanced by using suffix trees to store
      the huge amount of data being produced. A test set of 110 sequencing primers and
      11 PCR primer pairs has been designed on genomic templates, cDNAs and sequences
      containing repetitive elements to analyze PRIDE's success rate. The high
      performance of PRIDE, combined with its minimal requirement of user interaction
      and its fast algorithm, make this program useful for the large scale design of
      primers, especially in large sequencing projects.

PMID- 9611249
TI  - Transposon Tc1 of the nematode Caenorhabditis elegans jumps in human cells.
AB  - The transposon Tc1 of the nematode Caenorhabditis elegans is a member of the
      widespread family of Tc1/mariner transposons. The distribution pattern of
      virtually identical transposons among insect species that diverged 200 million
      years ago suggested horizontal transfer of the elements between species.
      Thishypothesis gained experimental support when it was shown that Tc1 and later
      also mariner transposons could be made to jump in vitro , with their transposase
      as the only protein required. Later it was shown that mariner transposons from
      one fruit fly species can jump in other fruit fly species and in a protozoan and,
      recently, that a Tc1-like transposon from the nematode jumps in fish cells and
      that a fish Tc1-like transposon jumps in human cells. Here we show that the Tc1
      element from the nematode jumps in human cells. This provides further support for
      the horizontal spread hypothesis. Furthermore, it suggests that Tc1 can be used
      as vehicle for DNA integration in human gene therapy.

PMID- 9611250
TI  - Unique organization and involvement of GAGA factors in transcriptional regulation
      of the Xenopus stromelysin-3 gene.
AB  - Expression of the matrix metalloproteinase (MMP) gene stromelysin-3 ( ST3 ) has
      been shown to be tightly associated with cell migration and apoptosis inmammals
      and amphibians. This contrasts with most other MMP genes. We demonstrate here
      that the Xenopus ST3 gene also has a structure distinct from other MMP genes,
      with its C-terminal half (the hemopexin domain) encoded by 4 instead of 6 exons,
      as in other MMP genes. Our primer extension analysis reveals the existence of two
      transcription start sites and at least one is needed for transcription of the
      promoter in transient transfection assays. Furthermore, our deletion analysis has
      demonstrated a requirement for at least one GAGA factor binding site for promoter
      function. In vitro DNA binding and mutational studies have provided strong
      evidence for the participation of GAGA or GAGA-like factors in transcriptional
      regulation of the frog ST3 gene. This contrasts with regulation of the human ST3
      promoter. These results suggest that the ST3 gene evolved prior to most other
      metalloproteinase genes and uses distinct regulation pathways to achieve similar
      expression profiles and serve similar functions in mammals and amphibians.

PMID- 9611251
TI  - Conservation and continuity of periodic bent DNA in genomic rearrangements
      between the c-myc and immunoglobulin heavy chain mu loci.
AB  - Periodic bent DNA was mapped in the human c- myc and immunoglobulin heavy chain
      mu (Ig mu) loci. A total of 12 DNA bend sites in the c- myc gene and 11 sites in
      the Ig mu locus were aligned at average intervals of 694.2 +/- 281.4 and 654.5 +/
      222.7 bp respectively. Although some of the bend sites retained the distance of
      700 bp, their periodicity was disturbed at several locations, including the exons
      of the c- myc gene and the enhancer element present in the Ig mu locus. Analysis
      of rearrangements that resulted in tumorigenesis of lymphocytes showed that the
      continuity of DNA bend sites was conserved in three lymphoma cell lines, Manca,
      BL22 and Ramos, suggesting that the genomic rearrangements gain stability by
      retaining their periodicity. This adds further evidence that the periodic bent
      DNA plays a crucial role in genomic structure.

PMID- 9611253
TI  - Functional and physical interactions between the estrogen receptor Sp1 and
      nuclear aryl hydrocarbon receptor complexes.
AB  - 17beta-Estradiol (E2) induces cathepsin D gene expression in MCF-7 human breast
      cancer cells and previous analyses of the proximal promoter region of this gene
      identified two functional enhancer sequences; namely an Sp1(N)23estrogen
      responsive element (ERE) half-site (-199 to -165) and an imperfect palindromic
      ERE (-119 to -107). A third region of the cathepsin D gene promoter (CD/L, -145
      to -119) was also E2 responsive in transient transfection assays. A GC-rich
      sequence which contains two overlapping Sp1 binding sites (-145 to -135) was
      responsible for ER-mediated transactivation and required formation of an ER/Sp1
      complex in which only the Sp1 protein bound DNA. E2 responsiveness of the CD/L
      sequence was also dependent on an adjacent overlapping GCGTG motif corresponding
      to the dioxin-responsive element (DRE) core binding sequence, which is the
      cognate response element for the heterodimeric aryl hydrocarbon receptor
      (AhR)/AhR nuclear translocator (ARNT) transcription factor complex. The results
      show that ER-mediated transactivation of CD/L was associated with the Sp1(N)2
      4DRE (core) motif and involved formation of a multiprotein ER/Sp1-AhR/ARNT
      complex. These results illustrate a unique example of an endogenous role for
      AhR/ARNT in the absence of added AhR agonist and indicate that the cathepsin D
      gene proximal promoter region contains at least three different functional motifs
      associated with ER-mediated transactivation.

PMID- 9611252
TI  - Use of RDA analysis of knockout mice to identify myeloid genes regulated in vivo
      by PU.1 and C/EBPalpha.
AB  - PU.1 and C/EBPalpha are transcription factors essential for normal myeloid
      development. Loss-of-function mutation of PU.1 leads to an absolute block in
      monocyte/macrophage development and abnormal granulocytic development while that
      of C/EBPalpha causes a selective block in neutrophilic differentiation. In order
      to understand these phenotypes, we studied the role of PU.1 and C/EBPalpha in the
      regulation of myeloid target genes in vivo . Northern blot analysis revealed that
      mRNAs encoding receptors for M-CSF, G-CSF and GM-CSF, were expressed at low
      levels in PU.1(-/-) fetal liver compared with wild type. To identify additional
      myeloid genes regulated by PU.1 and C/EBPalpha, we performed representational
      difference analysis (RDA), a PCR-based subtractive hybridization using fetal
      livers from wild type and PU.1 or C/EBPalpha knockout mice. By introducing a new
      modification of RDA, that of tissue-specific gene suppression, we could
      selectively identify a set of differentially expressed genes specific to myeloid
      cells. Differentially expressed genes included both primary and secondary granule
      protein genes. In addition, eight novel genes were identified that were
      upregulated in expression during myeloid differentiation. These methods provide a
      general strategy for elucidating the genes affected in murine knockout models.

PMID- 9611255
TI  - Detection of differentially expressed genes in primary tumor tissues using
      representational differences analysis coupled to microarray hybridization.
AB  - The identification of differential gene expressionbetween cells is a frequent
      goal in modern biological research. Here we demonstrate the coupling of
      representational difference analysis (RDA) of cDNA with microarray analysis of
      the output for high throughput screening. Two primary Ewing's sarcoma tissue
      samples with different biological behavior in vivo were compared by RDA: one
      which was metastatic and progressed rapidly; the other localized and successfully
      treated. A modified RDA protocol that minimizes the necessary starting material
      was employed. After a reduced number of subtractive rounds, the output of RDA was
      shotgun cloned into a plasmid vector. Inserts from individual colonies from the
      subtracted library were amplified with vector-specific primers and arrayed at
      high density on glass slides. The arrays were then hybridized with differentially
      fluorescently labeled starting amplicons from the two tissues and fluorescent
      signals were measured at each DNA spot. We show that the relative amounts of
      fluorescent signal correlate well with the abundance of fragments in the RDA
      amplicon and in the starting mRNA. In our system, we analyzed 192 products and
      173 (90%) were appropriately detected as being >2-fold differentially expressed.
      Fifty unique, differentially expressed clones were identified. Therefore, the use
      of RDA essentially provides an enriched library of differentially expressed
      genes, while analysis of this library with microarrays allows rapid and
      reproducible screening of thousands of DNA molecules simultaneously. The coupling
      of these two techniques in this system resulted in a large pool of differentially
      expressed genes.

PMID- 9611254
TI  - Use of capillary electrophoresis in the study of ligand-DNA interactions.
AB  - Free solution capillary electrophoresis (FSCE) has been used to separate two non
      self-complementary 12mer oligonucleotide duplexes: d(AAATTATATTAT).d(ATAA
      TATAATTT) and d(GGGCCGCGCCGC).d(GCGGCGCGGCCC). Titration of mixtures of the two
      oligonucleotides with model intercalators (ethidium bromide andactinomycin D) and
      minor groove binders (netropsin, Hoechst 33258 and distamycin) has shown the
      suitability of FSCE as a method to study the sequence selectivity of DNA binding
      agents. Binding data have shown cooperativity of binding for netropsin and
      Hoechst 33258 and have provided ligand:DNA binding ratios for all five compounds.
      Cooperativity of netropsin binding to a 12mer with two potential sites has been
      demonstrated for the first time. Ligands binding in the minor groove caused
      changes in migration time and peak shape which were significantly different from
      those caused by intercalators.

PMID- 9611256
TI  - The influence of 3TC resistance mutation M184I on the fidelity and error
      specificity of human immunodeficiency virus type 1 reverse transcriptase.
AB  - A common target for therapies against human immuno-deficiency virus type 1 (HIV
      1) is the viral reverse transcriptase (RT). Treatment with the widely used
      nucleoside analog (-)-2', 3'-deoxy-3'-thiacytidine (3TC) leads to the development
      of resistance-conferring mutations at residue M184 within the YMDD motif of RT.
      First, variants of HIV with the M184I substitution appear transiently, followed
      by viruses containing the M184V substitution, which persist and become the
      dominant variant for the duration of therapy. In the three-dimensional crystal
      structure of HIV-1 RT complexed with double-stranded DNA, the M184 residue lies
      in the vicinity of the primer terminus, near the incoming dNTP substrate. Recent
      studies have shown that 3TC resistance mutations, including M184I, increase the
      nucleotide insertion and mispair extension fidelity. Therefore, we have examined
      the effects of the M184I mutation on the overall polymerase fidelity of HIV-1 RT
      via an M13-based forward mutation assay. We found the overall error rate of the
      M184I variant of HIV-1 RT to be 1.7 x 10(-5) per nucleotide. This represents a 4
      fold increase in fidelity over wild-type HIV-1Hxb2RT (7.0 x 10(-5) per
      nucleotide) and a 2.5-fold increase in fidelity over the M184V variant (4.3 x 10(
      5) per nucleotide). Of the nucleoside analog resistance mutations studied using
      the forward assay, the M184I variant has shown the greatest increase in fidelity
      observed to date. Interestingly, the M184I variant RT displays significantly
      altered error specificity, both in terms of error rate at specific sites and in
      the overall ratio of substitution to frameshift mutations in the entire target.

PMID- 9611257
TI  - Detection of known mutation by proof-reading PCR.
AB  - Proof-reading PCR (PR-PCR) is designed to detect known mutations within genomic
      DNA. It differs from standard PCR approaches in that one of the two primers has
      its 3' end aligned with a putative mutation site, and has its 3'-OH replaced by a
      blocking group. Distinguishing a mutant gene from wild-type depends upon
      preferential removal of the blocked 3' terminal nucleotide by the polymerase
      proof-reading activity when it is mismatched with the template. Preferential
      removal of the blocked nucleotide allows subsequent extension and selective
      amplification, and provides the basis for distinguishing mutant from normal
      genes. This method has been used here to detect a transition mutation within the
      P53 gene of HaCaT cells with verification by direct sequencing of the selectively
      amplified DNA.

PMID- 9611258
TI  - Direct binding to nucleic acids by Vpr of human immunodeficiency virus type 1.
AB  - Human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) is a 15kDa
      regulatory protein packaged in the HIV-1 virion. Although the molecular mechanism
      of Vpr function during viral replication remains elusive, Vpr has been found to
      possess interesting biological activities, including cell-cycle arrest at the
      G2/M check point, promotion of the HIV-1 pre-integration complex for nuclear
      transport, and a low but significant level of transcriptional activation of a
      variety of viral and cellular promoters. We now present data suggesting that HIV
      1 Vpr is a nucleic-acid-binding protein. This activity of Vpr was demonstrated by
      DNA-cellulose chromatography, antibody co-immunoprecipitation, and gel
      electrophoretic mobility shift assays. By mutational analysis, the C-terminal
      region of Vpr, which is rich in basic amino-acid residues, was shown to be
      critical for Vpr binding to nucleic acids. The nucleic-acid-binding activity of
      Vpr is consistent with several biological activities of Vpr and may provide an
      important clue for understanding the molecular interactions between HIV-1 and the
      host cells.

PMID- 9611259
TI  - The Bacillus stearothermophilus argCJBD operon harbours a strong promoter as
      evaluated in Escherichia coli cells.
AB  - We have shown that the B. stearothermophilus argCJBD genes form a single operon.
      In B. stearothermophilus, a specific repressor governs operon expression by
      binding to the argCo operator site overlapping the Parg promoter sequence (Dion
      et al., 1997). Therefore, the enzymatic and transcriptional analyses performed in
      this work did not reflect the potential strength of Parg in the native host. For
      evaluation of the Parg promoter strength, E. coli was used as a host since its
      own ArgR repressor does not interact with the B. stearothermophilus heterologous
      operator. Parg-promoted argC gene expression dramatically increased, reaching up
      to 38% of the total protein in E. coli cells. An AT-rich sequence upstream of a 
      35 site of Parg was found to be indispensable for the promoter strength. Plasmids
      carrying the B. stearothermophilus argCJBD operon linked with its Parg/argCo
      region were unstable in E. coli. Stabilization of plasmids was achieved by
      repression of B. stearothermophilus arg genes through the action of the B.
      subtilis AhrC repressor.

PMID- 9611260
TI  - Characterization of yhcN, a new forespore-specific gene of Bacillus subtilis.
AB  - A new Bacillus subtilis sporulation-specific gene, yhcN, has been identified, the
      expression of which is dependent on the forespore-specific sigma factor sigmaG
      and to a much lesser extent on sigmaF. A translational yhcN-lacZ fusion is
      expressed at a very high level in the forespore, and the protein encoded by yhcN
      was detected in the inner spore membrane. A yhcN mutant sporulates normally and
      yhcN spores have identical resistance properties to wild-type spores. However,
      the outgrowth of yhcN spores is slower than that of wild-type spores.

PMID- 9611261
TI  - The influence of the 5' codon context on translation termination in Bacillus
      subtilis and Escherichia coli is similar but different from Salmonella
      typhimurium.
AB  - The last two amino acids in the nascent peptide influence translation termination
      in E. coli (Mottagui-Tabar et al., 1994; Bjornsson et al., 1996). We have
      compared the effects on termination in Escherichia coli, Bacillus subtilis and
      Salmonella typhimurium obtained by varying the -1 and -2 codons upstream of the
      weak UGAA stop signal. The peptide effect from the penultimate amino acid on
      translation termination in B. subtilis is similar to that seen in E. coli (with
      66.5% RF-2 amino acid sequence similarity), whereas the influence in S.
      typhimurium (with 95.3% similarity to E. coli) is weaker. The effect of changing
      the -1 codon (P-site) is weaker in S. typhimurium as compared to those in E. coli
      and B. subtilis. RF-2s from E. coli and S. typhimurium have a threonine or
      alanine at position 246, respectively. This amino acid exchange in RF-2 can
      explain the difference in efficiency and toxicity during overexpression when E.
      coli and S. typhimurium are compared (Uno et al., 1996). However, B. subtilis RF
      2 also has an alanine at that position, yet the sensitivity to the nascent
      peptide is similar to that in E. coli. Thus, the amino acid difference at
      position 246 in the RF-2 sequences cannot explain why termination in E. coli and
      B. subtilis is similar in peptide sensitivity while being different from that in
      S. typhimurium. Sequence alignments of RF-2 from the three bacteria show other
      regions of the molecule that could be involved in the functional interactions
      with the C-terminal end of the nascent peptide.

PMID- 9611262
TI  - YIpDCE1 - an integrating plasmid for dual constitutive expression in yeast.
AB  - YIpDCE1 (Dual Constitutive Expression), a novel Saccharomyces cerevisiae
      integrating plasmid, constitutively expresses two genes under the control of
      separate phosphoglycerol kinase promoters. YIpDCE1 contains the complete ADE2
      gene which can be used as a marker for selecting integrants at mutant ade2 loci
      commonly present in laboratory yeast strains. The YIpDCE1 plasmid can be inserted
      into the ade2-101 locus of the HF7c strain used in two hybrid screens. Thus it
      could be useful for analysis of two hybrid interactions that occur in the context
      of additional protein components (e.g. modifying enzymes such as kinases or
      phosphatases, or multimeric complexes consisting of three or four distinct
      protein components). YIpDCE1 has been used to create strains simultaneously
      overexpressing the permease (FTR1) and oxidase (FET3) components of the yeast
      high-affinity iron uptake system. This confers constitutive high-affinity iron
      uptake on the transformed strains, bypassing the normal regulatory mechanisms.

PMID- 9611263
TI  - The arbZ gene from Lactobacillus delbrueckii subsp. lactis confers to Escherichia
      coli the ability to utilize the beta-glucoside arbutin.
AB  - From a genomic library of the industrially used strain Lactobacillus delbrueckii
      subsp. lactis DSM7290, a gene designated arbZ (869bp; encoding a 33.5kDa protein)
      was isolated by screening E. coli transformants for the ability to utilize the
      beta-glucoside arbutin. Out of 9000 transformants nine were able to ferment
      arbutin, whereas no utilization of the beta-glucosides salicin, esculin or
      cellobiose could be detected. Overexpression of arbZ using the T7-polymerase-T7
      promoter-system resulted in the formation of insoluble, catalytically inactive
      protein aggregates (inclusion bodies). Accordingly, overexpression was not
      accompanied by an increase in ArbZ activity. Induction of arbZ controlled by the
      lac promoter under conditions that reduce protein aggregation resulted in a 12
      fold increase in arbutin hydrolyzing activity of intact cells and a 13-fold
      increase in phospho-beta-glycosidase activity in cell-free extracts of the
      respective transformants. Nucleotide sequence analysis revealed a second gene
      upstream of arbZ that was designated arbX (830bp). ArbX (32.6kDa) shared
      similarity with several glycosyltransferases involved in the biosynthesis of
      lipopolysaccharides in Gram-negative bacteria. In Lb. delbrueckii subsp. lactis
      DSM7290 two transcripts, one covering arbX together with arbZ and one covering
      arbZ alone were detected by Northern blot analysis.

PMID- 9611264
TI  - Murine branched chain alpha-ketoacid dehydrogenase kinase; cDNA cloning, tissue
      distribution, and temporal expression during embryonic development.
AB  - These studies were designed to demonstrate the structural and functional
      similarity of murine branched chain alpha-ketoacid dehydrogenase and its
      regulation by the complex-specific kinase. Nucleotide sequence and deduced amino
      acid sequence for the kinase cDNA demonstrate a highly conserved coding sequence
      between mouse and human. Tissue-specific expression in adult mice parallels that
      reported in other mammals. Kinase expression in female liver is influenced by
      circadian rhythm. Of special interest is the fluctuating expression of this
      kinase during embryonic development against the continuing increase in the
      catalytic subunits of this mitochondrial complex during development. The need for
      regulation of the branched chain alpha-ketoacid dehydrogenase complex by kinase
      expression during embryogenesis is not understood. However, the similarity of
      murine branched chain alpha-ketoacid dehydrogenase and its kinase to the human
      enzyme supports the use of this animal as a model for the human system.

PMID- 9611265
TI  - PCR isolation of catechol 2,3-dioxygenase gene fragments from environmental
      samples and their assembly into functional genes.
AB  - A method was developed to isolate central segments of catechol 2, 3-dioxygenase
      (C23O) genes from environmental samples and to insert these C23O gene segments
      into nahH (the structural gene for C23O encoded by catabolic plasmid NAH7) by
      replacing the corresponding nahH sequence with the isolated segments. To PCR
      amplify the central C23O gene segments, a pair of degenerate primers was designed
      from amino acid sequences conserved among C23Os. Using these primers, central
      regions of the C23O genes were amplified from DNA isolated from a mixed culture
      of phenol-degrading or crude oil-degrading bacteria. Both the 5' and 3' regions
      of nahH were also PCR-amplified by using appropriate primers. These three PCR
      products, the 5'-nahH and 3'-nahH segments and the central C23O gene segments,
      were mixed and PCR-amplified again. Since the primers for the amplification of
      the central C23O gene segments were designed so that the 20 nucleotides at both
      ends of the segments are identical to the 3' end of the 5'-nahH segment and the
      5' end of the 3'-nahH segment, respectively, the central C23O gene segments could
      anneal to both the 5'- and 3'-nahH segments. After the second PCR, hybrid C23O
      genes in the form of (5'-nahH segment-central C23O gene segment-3'-nahH segment)
      were amplified to full length. The resulting products were cloned into a vector
      and used to transform Escherichia coli. This method enabled divergent C23O
      sequences to be readily isolated, and more than 90% of the hybrid plasmids
      expressed C23O activity. Thus, the present method is useful to create, without
      isolating bacteria, a library of functional hybrid genes.

PMID- 9611266
TI  - Structure and expression of the human septin gene HCDCREL-1.
AB  - Septins are a family of highly conserved filament-forming proteins that have been
      shown to mediate cytokinesis and cytoskeletal organization in fungi and
      Drosophila. The gene encoding the human septin family member HCDCREL-1 has been
      shown to be transcribed from a locus immediately adjacent to that of the platelet
      glycoprotein (GP) Ib b. The HCDCREL-1 gene possesses a non-consensus
      polyadenylation signal that apparently is not efficiently utilized, resulting in
      the expression of a readthrough transcript also containing the platelet GPIb beta
      coding region. As a first step in understanding the regulation and function of
      HCDCREL-1, we have analyzed the structure of this gene and characterized its
      expression in a variety of human cells. Our results indicate that the gene is
      expressed at high levels in platelets and neural tissue, and is transcriptionally
      complex.

PMID- 9611267
TI  - Isolation of a Drosophila T-box gene closely related to human TBX1.
AB  - T-box genes, in all metazoans studied from nematode to man, exist in small gene
      families. They encode transcription factors with a novel, large, and highly
      conserved DNA binding domain termed the T-domain. In all cases studied, T-box
      genes have important developmental roles. Two familial diseases, Holt-Oram
      syndrome and ulnar-mammary syndrome, were recently shown to be caused by
      mutations in the human T-box genes TBX5 and TBX3, respectively. T-box genes were
      first identified in Drosophila and mouse. Two of the three known Drosophila T-box
      genes show a close sequence homology to mammalian genes. Similarities in the
      phenotypes of fly and mammalian mutants can be taken as evidence of functional
      conservation. We report here the isolation of a fourth Drosophila T-box gene,
      optomotor-blind-related gene-1 (org-1), closely related to mouse and human TBX1.
      We localized TBX1 to chromosomal band 22q11, confirming a recent report, and
      discuss TBX1 as a candidate gene for DiGeorge and related syndromes.

PMID- 9611268
TI  - The Arabidopsis SHAGGY-related protein kinase (ASK) gene family: structure,
      organization and evolution.
AB  - Higher plants contain a multigene family encoding proteins that share a highly
      conserved catalytic protein kinase domain about 70% identical to SHAGGY protein
      kinase (SGG) and glycogen synthase kinase-3 (GSK-3), respectively, from
      Drosophila and mammals. In this study we have characterized the structure and
      evolution of the Arabidopsis SHAGGY-related protein kinase (ASK) gene family. At
      least ten ASK genes are present per haploid genome of Arabidopsis. The genomic
      sequences of five ASK genes show a strikingly high conservation of intron
      positions and exon lengths. Phylogenetic analyses suggested that the Arabidopsis
      gene family contains at least three ancient classes of genes that diverged early
      in land plant evolution. The different classes may reflect specificity of
      substrates and/or biological functions. Eight out of the ten predicted ASK genes
      were mapped and shown to be dispersed over the five Arabidopsis chromosomes. A
      tentative model for the organization and evolution of the Arabidopsis ASK genes
      is presented.

PMID- 9611269
TI  - Secretory ribonuclease genes and pseudogenes in true ruminants.
AB  - Mammalian pancreatic ribonucleases (RNase) form a family of extensively studied
      homologous proteins. Phylogenetic analyses, based on the primary structures of
      these enzymes, indicated that the presence of three homologous enzymes
      (pancreatic, seminal and brain ribonucleases) in the bovine species is due to
      gene duplication events, which occurred during the evolution of ancestral
      ruminants. In this paper the sequences are reported of the coding regions of the
      orthologues of the three bovine secretory ribonucleases in hog deer and roe deer,
      two deer species belonging to two different subfamilies of the family Cervidae.
      The sequences of the 3' untranslated regions of the three different secretory
      RNase genes of these two deer species and giraffe are also presented. Comparison
      of these and previously determined sequences of ruminant ribonucleases showed
      that the brain-type enzymes of giraffe and these deer species exhibit variations
      in their C-terminal extensions. The seminal-type genes of giraffe, hog deer and
      roe deer show all the features of pseudogenes. Phylogenetic analyses, based on
      the complete coding regions and parts of the 3' untranslated regions of the three
      different secretory ribonuclease genes of ox, sheep, giraffe and the two deer
      species, show that pancreatic, seminal- and brain-type RNases form three separate
      groups.

PMID- 9611270
TI  - The gene and processed pseudogenes of the rat mitochondrial single-strand DNA
      binding protein: structure and promoter strength analyses.
AB  - The gene for the rat mitochondrial single-stranded DNA-binding protein (mtSSB)
      was amplified by PCR and isolated as several overlapping genomic clones. The
      clones encompassed the 5' untranslated sequence and all intron/exon junctions.
      The gene contained seven exons and six introns. The first exon contained only 5'
      untranslated sequence. The 16-amino acid mitochondrial targeting presequence,
      encoded by the second and third exons, was precisely bisected by intron 2. All
      intron donor and acceptor sites were consistent with the GT/AG consensus. The
      transcription start site was determined by primer-extension analysis to be 69bp
      upstream of the translation start codon. The upstream sequence lacked TATA and
      CCAAT boxes at the expected locations, but did contain several other potential
      regulatory elements including a GC box (Sp1-binding site) and three NRF-2 sites,
      one of which was located precisely beside the transcription start site. A 10 out
      of 12 imperfect NRF-1 site was located within the first exon. The 5' flanking
      sequence (-546 to +30) was shown to have strong promoter activity in transient
      transfection assays in primary rat hepatocytes and HepG2 cells. In addition,
      evidence for the existence of several mtSSB processed pseudogenes was obtained.
      These pseudogenes lacked introns and contained substitution and deletion
      mutations compared to the cDNA sequence. The 5' upstream region of one of the
      pseudogenes was analyzed and found to contain negligible promoter activity.

PMID- 9611271
TI  - Molecular cloning of a cDNA encoding a silkworm protein that contains the
      conserved BH regions of Bcl-2 family proteins.
AB  - To search for a Bcl-2 family homologue in the posterior silk gland of Bombyx
      mori, Western blot analysis was performed with the anti-rat Bcl-XL antiserum
      preabsorbed with a XL1-Blue MRF' lysate. The antiserum was shown to cross-react
      specifically with a silkworm protein of 80000 mol. wt (BmP80). The level of BmP80
      increased dramatically during the spinning stage and decreased rapidly after the
      formation of a cocoon, implying that the silkworm protein was involved in
      histolysis of posterior silk gland as a stimulator. Screening a B. mori cDNA
      library with the same preabsorbed antiserum, a cDNA clone contaiing a cDNA
      fragment that is presumably large enough to encode the entire BmP80 protein was
      identified. The cDNA fragment contained 127 nucleotides (nt) of untranslated
      sequence at the 5' end, 2895nt of presumptive coding sequence and 625nt of
      untranslated sequence including a poly(A) tail at the 3' end. The calculated mol.
      wt of the presumptive protein (BmP109) was 108800. BmP109 shared sequence
      homology with the antiapoptotic proteins within the four conserved regions, BH1,
      BH2, BH3 and BH4, which were located at the C-terminal half of the protein and
      resided in the same characteristic order as Bcl-2 family proteins. Comparison of
      amino acid content revealed that BmP109 contained much more cysteine and lysine
      but less glycine and arginine than the antiapoptotic proteins. Northern blot
      analysis indicated that the mRNA for BmP109 is about 4.0kb. Reverse transcription
      polymerase chain reaction experiments showed that the mRNA level for BmP109
      increased dramatically during the spinning stage and decreased rapidly after
      formation of a cocoon, suggesting the involvement of transcriptional regulation.

PMID- 9611272
TI  - Usage of non-canonical promoter sequence by the yeast mitochondrial RNA
      polymerase.
AB  - Prior work has demonstrated that a conserved nonanucleotide [5'-TATAAGTAA(+2)]
      promoter sequence is used by the mitochondrial [mt]1 RNA polymerase in
      Saccharomyces cerevisiae. However, the highly AT-rich yeast mt genome carries
      many other promoter-like sequences, but only a fraction of them are involved in
      gene-specific transcription. To examine the sequence variability of this
      nonanucleotide promoter motif, single or multiple nt substitutions were
      introduced into the canonical promoter sequence. The transcriptional activity of
      these altered promoter sequences was examined under the in-vitro reaction
      conditions. The results presented here determined that several variant promoter
      sequences (i. e. TAAAAGTAA, TATAAGAAA, TATAAGTAG, TATAAGAAG, TATAAGAGA,
      TATAAGGGA, TATAAGTGG, TAAAAGTAG) were efficiently used by the mtRNA polymerase.
      However, a single (i.e. AATAAGTAA, TTTAAGTAA, TATTAGTAA, TATAACTAA, TATAAGGAA,
      TATAAGTAT) or multiple (TATAGGAAA, TAAAAGGAA, TATAGGGAA, TAAAGGAAA, TAAAGGGAA) nt
      substitution(s) in other locations drastically reduced mt promoter function.
      Interestingly, some of these poorly or partially active promoter variants (i.e.
      TATAAGGAA, TATAAGTAT, TATAAGTCA) became fully functional in the presence of
      sequence-specific dinucleotide primer. Since dinucleotide primer bypasses the
      first phosphodiester bond formation in transcription, it is suggested that the 
      1T-->G, +1A-->C and +2A-->T mutations affect mt transcription at the level of
      initiation rather than polymerase binding.

PMID- 9611273
TI  - Recombination trapping: an in-vivo approach to recover cDNAs encoded in YACs.
AB  - We have developed an approach to identify and localize cDNAs encoded by YACs. In
      this scheme, a YAC truncation vector containing a cDNA library is used to
      interrupt the YAC by homologous recombination in yeast. This approach generates
      YACs truncated at the site of recombination between the cDNA and the cognate YAC
      sequence and thus localizes the gene in the YAC. This method results in the
      production of a large percentage of true recombinants identifying gene encoding
      regions of the genome. This approach is shown to identify an unique EST sequence
      from a YAC in Xp22, the recently described transketolase-like gene in a YAC from
      Xq28 and a putative kinesin-like gene in Xq13. This system should also be useful
      in the mapping of YACs by targeted integration. We have constructed a new
      telomere truncation vector, pGR8, which incorporates two selectable markers, HIS5
      and LYS2. This vector overcomes problems of previous vectors including:
      incompatibility with most YAC libraries, vector homology with the YAC arms and
      high backgrounds resulting from the use of a single selectible marker. A third
      counterselection with 5-fluoroorotic acid (5FOA) against yeast clones retaining
      the URA3 gene was also employed to reduce background further. Therefore, this
      vector and approach should be useful to the transcriptional analysis of YAC maps
      of any genome.

PMID- 9611275
TI  - Editorial 

PMID- 9611274
TI  - Isolation and characterization of a new gene encoding a member of the HIRA family
      of proteins from Drosophila melanogaster.
AB  - The HIRA family of genes (named after yeast HIR genes; HIR is an acronym for
      'histone regulator') includes the yeast HIR1 and HIR2 repressors of histone gene
      transcription in S. cerevisiae, human TUPLE-1/HIRA, chicken HIRA, and mouse HIRA.
      Here, we describe a new member of the HIRA family, Dhh, for the Drosophila
      homolog of HIRA . Northern analysis with poly (A)+ mRNA isolated from different
      developmental stages of Drosophila melanogaster shows hybridization with a single
      Dhh transcript of 4.1kb. Hybridization is strong in female adults, unfertilized
      eggs and 0-3-h-old embryos, then diminishes, but is still detectable, during
      later stages of development and in adult males. More specifically, in-situ
      hybridization shows that Dhh transcripts, which are initially detected in nurse
      cells during mid-oogenesis, become localized to the developing oocyte at high
      levels. Transcripts persist strongly during early blastoderm stages then fade
      dramatically by 3h of development. The Dhh cDNA encodes an open reading frame of
      1061 amino acids with high similarity scores to the HIRA polypeptides, as well as
      two hypothetical polypeptides from C. elegans and S. pombe, in a protein database
      search. They all share three highly homologous regions: a WD-repeat cluster, a
      small domain with clustered positively charged amino acids, and a domain
      comprising two repeats with close resemblance to WD repeats plus a region with no
      homology outside of the family. The conservation of these homologous regions in
      HIRA-encoded proteins from evolutionary distant organisms suggests that they are
      important for the activity of the members of the family.

PMID- 9611276
TI  - [Gammography using Tc 99m MIBI in patients with suspected breast cancer. Proposed
      diagnostic protocol].
AB  - The aim of this work has been to determine whether the joint use of mammography
      and scintimammography is capable of reducing the number of biopsies required in
      patients with suspected breast cancer. We have performed scintimammography in 90
      patients, 97 lesions, with breast cancer suspicion. In the mammography was
      evaluated the degree of malignancy suspicion and the size of the lesion. Only 41
      of the biopsies revealed the presence of cancer. The sensitivity, specificity,
      PPV and NPV of scintimammography were 85%, 79%, 74% and 88%. According to the
      mammography findings 20 lesions (1 breast cancer) were included as low, 31
      lesions (4 breast cancer) as indeterminate and 46 lesions (36 breast cancer) as
      high malignancy suspicion. 14 lesions (2 low, 2 indeterminate and 10 high
      suspicion) were smaller than 1 cm. The scintimammography was positive in all
      breast cancer of low and indeterminate suspicion of malignancy and in 30 of high
      probability. On the basis of this results we propose that a biopsy must be
      carried out to those lesions with a high suspicion of malignancy, and to lesions
      with low or indeterminate suspicion that are smaller than 1 cm or that present a
      positive scintimammography. Following this protocol, only 64 of the 97 biopsies
      would have been necessary, with a reduction of the 34% in the total number of
      biopsies and, more important, a 65% of reduction in the number of biopsies
      carried out in the groups of low and indeterminate suspicion of malignancy. At
      the same time we would indicate biopsy in all cases of breast cancer.

PMID- 9611277
TI  - [Radiolabeling of a new agent for the study of colorectal tumors].
AB  - A new Monoclonal Antibody (AcMo) ior-C5, highly specific for the most part of
      colorectal adenocarcinomas has been developed. The AcMo was labeled with 99mTc by
      the Schwarz's direct method using molar ratios MAb: reductant of 1:1,000 and
      1:2,000. The first molar ratio was the most adequate for the preparation of the
      radiopharmaceutical. A labeling yield greater than 95% was obtained. Several <<in
      vitro>> assays were carried out in order to evaluate the stability of the
      preparation, whose results reflected the presence of the stable complex 99mTc
      IgG. The biodistribution patterns for both preparations were similar. The
      excreting organs behaved like normal. Nevertheless, a greater renal excretion was
      observed for the preparation of the molar ratio of 1:2.000, which could be due to
      the presence of low affinity sites observed in this preparation. They are
      vulnerable to the trans-chelation of the 99mTc toward cysteine or glutathione
      present in plasma and tissues.

PMID- 9611278
TI  - [Scintigraphic images im primary hyperparathyroidism with 99m Tc-Tetrofosmin].
AB  - To evaluate the scintigraphy images of 99mTc-tetrofosmin in the primary
      hyperparathyroidism, we studied 8 patients, 5 males, with ages between 17 and 82
      (median = 50) years old, and with clinical and laboratory manifestations of
      hyperparathyroidism (calcium metabolism and PTH elevated); parathyroid
      scintigraphy was realized after 20mCi (740 MBq) intravenously injection of 99mTc
      tetrofosmin, and were acquired images (10, 60 and 120 min.) in a large field
      gamma camera. All patients were submitted to surgery. The histology of surgical
      specimens showed seven adenomas and one adenocarcinoma of parathyroids; the
      scintigraphic images showed four lesions in the inferior right lobe and four in
      the inferior left lobe of thyroid and have global correlation with surgical
      findings. There was preferential retention of the tracer in the earlier images
      (10 min) in all cases (100%) and in the later images (120 min.) in 5 cases
      (62.5%). In conclusion, the earlier images (10 min) were more diagnostic than the
      later in the primary hyperparathyroidism study. It is possible that other tumoral
      lesions have similar behavior with 99mTc-tetrofosmin.

PMID- 9611279
TI  - [Use of 99mTc-tetrofosmin scintigraphy in the diagnosis of patients with
      hyperparathyroidism].
AB  - The aim of the work was to study the diagnostic value of 99mTc-tetrofosmin to
      localize anomalous parathyroid glands in patients with hyperparathyroidism.
      METHODS: We have studied 33 patients: 12 with primary and 21 with secondary
      hyperparathyroidism, 9 of them renal graft recipients. Sixteen patients underwent
      surgery, 12 with primary and 4 with secondary hyperparathyroidism. All patients
      were injected with 740 MBq of 99mTc-tetrofosmin. Subsequently at 15, 30 and 60
      minutes images were acquired for 300 seconds using a pin-hole collimator. A
      pertechnetate thyroid scintigraphy was obtained in 7 cases (24-48 h later) when
      the thyroid activity made difficult the identification of parathyroid glands.
      RESULTS: In the group of patients with primary hyperparathyroidism, all cases
      showed a focal uptake in lower right localization. In the secondary
      hyperparathyroidism group, 12 patients showed diffuse tracer uptake in two or
      more glands and histology confirmed hyperplasia in four of them. Seven cases
      showed a greater focal uptake in a gland: two of them were renal graft recipients
      and three were chronic renal failure cases in haemodyalisis, and two were
      evaluated postsurgery showing uptake in the remnant parathyroid gland. The two
      remaining patients had a normal scintigraphy and corresponded to two false
      negative cases. In conclusion, our results suggest that 99Tc-tetrofosmin may be
      used as a suitable tracer for preoperative detection and screening of anomalous
      parathyroid glands.

PMID- 9611280
TI  - [99m Tc-sestamibi in the diagnosis of the location of hyperparathyroidism].

PMID- 9611281
TI  - [False positive with Tl-201 in the study of Ewing's sarcoma of the astragalus
      caused by reflex sympathetic dystrophy].
AB  - We describe a 14 year old male, diagnosed of Ewing sarcoma in left astragalus. We
      performed two 201-Thallium scan for evaluating the response to chemotherapy
      (before and after the treatment). The scan performed after chemotherapy showed
      patchy uptake in astragalus, calcaneus and some joints of the foot. The following
      radiology and scintigraphy diagnosed a reflex sympathetic dystrophy in the left
      foot due to disuse of the limb. The 201-Thallium overestimated viability of the
      tumour for this reason. We must discard the presence of this kind of associated
      pathology in order that they could be cause of false positives.

PMID- 9611282
TI  - [Hepatopulmonary syndrome and pulmonary perfusion scan].
AB  - We introduce you a case report of a female patient who has got a chronic liver
      disease and who entered our hospital with clinical suspicion of pulmonary
      embolism. The radionuclide lung perfusion scan using 99m Technetium-labelled with
      macroaggregated albumin, showed an abnormal uptake out of the lungs in liver,
      spleen, and kidneys. Once all possible etiologies of extrapulmonary uptake were
      excluded and confirming that the hepatopulmonary syndrome clinical criteria were
      coincident with our case, we attribute that the abnormal extrapulmonary uptake
      was explainable due to this syndrome. This is an hepatopulmonary syndrome case in
      which nuclear medicine techniques were decisive for the diagnosis in front of
      other diagnostic tests (radiography, echography and CT) that gave valuable but
      non conclusive information.

PMID- 9611284
TI  - [Hepatobiliary radioisotopic scanning: method and clinical applications].

PMID- 9611283
TI  - [Muscle uptake of 18FDG in positron emission tomography].

PMID- 9611285
TI  - [Biochemical markers of calcium/phosphorus metabolism].

PMID- 9611287
TI  - News 

PMID- 9611286
TI  - [Comments on the technical report "PET in Oncology" from the Health Technology
      Evaluation Agency of the Carlos III Health Institute].

PMID- 9611288
TI  - Esophageal peristalsis: the role of deglutitive inhibition in normal subjects and
      patients with dysphagia.

PMID- 9611289
TI  - Demonstration of the deglutitive wave of inhibition by extrinsic esophageal
      vascular compression.
AB  - In the human esophagus a wave of inhibition precedes the primary peristaltic
      contraction. To study this wave of deglutitive inhibition an artificial high
      pressure zone has to be created in the esophageal body. The inflation of an
      intraesophageal balloon is the way to demonstrate the inhibition. In this paper
      we show another possibility of manometric recording of esophageal deglutitive
      inhibition. Esophageal extrinsic vascular compression may cause a zone of high
      pressure in the esophageal body which can be seen in all segments of the
      esophagus. With deglutition there is a relaxation in this zone that precedes the
      primary peristaltic contraction.

PMID- 9611290
TI  - Laryngeal mobility and dysphagia.
AB  - The authors studied the utility of the physical test of laryngeal movement in
      swallowing disorders of the oropharyngeal region. Measurement and palpation of
      the larynx during deglutition were performed in the neck of 14 dysphagic patients
      and in two normal control groups. The normal groups were used to establish the
      pattern of the movement and the normal values of laryngeal elevation. Control
      elevation ranged from 1.80 to 2.50 cm. In eight patients laryngeal motion was
      defective and presented values ranging from zero to 1.50 cm. Palpation during
      laryngeal movement also revealed unexpected anomalous displacement such as
      lateral shifting and lowering of the larynx. In six patients with defective
      laryngeal motion, pharyngeal and upper esophageal sphincter function were also
      impaired. Direct measurement and palpation of laryngeal mobility during
      deglutition is a noninvasive method that can be used to evaluate dysphagia and
      the risk for aspiration. Also, it allows physical assessment of the evolution of
      the disorder.

PMID- 9611292
TI  - The screening sensitivity of endoscopy, acid perfusion test and 24-hour pH
      monitoring to evaluate esophagitis in patients with heartburn and histological
      esophagitis.
AB  - The sensitivity of endoscopic examinations, acid perfusion test and 24-hour
      esophageal pH-monitoring, were studied in patients with heartburn. Thirty six
      adult patients with histological esophagitis were included in this prospective
      study. Endoscopy showed esophageal lesion in 18/36 (sensitivity of 50%):
      esophagitis grade I in 10 (55.6%) and, grade II in eight (44.4%). Acid perfusion
      test was positive in 10/25 (sensitivity of 40%) of the patients submitted to the
      test. Twenty-four-hour pH-monitoring was positive in 17/29 patients (sensitivity
      of 58.6%): eight (61.5%) did not have esophageal lesion at endoscopy, two (25%)
      had esophagitis grade I and seven (87.5%) had esophagitis grade II. In the
      patients submitted to 24-hour pH-monitoring, a greater number or reflux episodes
      in orthostatic position than in supine position (P < 0.0001) was observed. The
      total number of reflux episodes, the most prolonged reflux and the total pH time
      < 4 were statistically higher in post-prandial period than during meals (P =
      0.005).

PMID- 9611291
TI  - Plasma levels of transthyretin and retinol-binding protein in Child-A cirrhotic
      patients in relation to protein-calorie status and plasma amino acids, zinc,
      vitamin A and plasma thyroid hormones.
AB  - Transthyretin and retinol-binding protein are sensitive markers of acute protein
      calorie malnutrition both for early diagnosis and dietary evaluation. A
      preliminary study showed that retinol-binding protein is the most sensitive
      marker of protein-calorie malnutrition in cirrhotic patients, even those with the
      mild form of the disease (Child A). However, in addition to being affected by
      protein-calorie malnutrition, the levels of these short half-life-liver-produced
      proteins are also influenced by other factors of a nutritional (zinc, tryptophan,
      vitamin A, etc) and non-nutritional (sex, aging, hormones, renal and liver
      functions and inflammatory activity) nature. These interactions were investigated
      in 11 adult male patients (49.9 +/- 9.2 years of age) with alcoholic cirrhosis
      (Child-Pugh grade A) and with normal renal function. Both transthyretin and
      retinol binding protein were reduced below normal levels in 55% of the patients,
      in close agreement with their plasma levels of retinol. In 67% of the patients
      (4/6), the reduced levels of transthyretin and retinol-binding protein were
      caused by altered liver function and in 50% (3/6) they were caused by protein
      calorie malnutrition. Thus, the present data, taken as a whole, indicate that
      reduced transthyretin and retinol-binding protein levels in mild cirrhosis of the
      liver are mainly due to liver failure and/or vitamin A status rather than
      representing an isolated protein-calorie malnutrition indicator.

PMID- 9611293
TI  - Kupffer cell activation with BCG. Corynebacterium parvum or zymosan protects
      against acute liver injury induced by carbon tetrachloride in rats.
AB  - Kupffer cells have been implicated in the pathogenesis of liver injury, but there
      is controversy about the effects of activation of these cells on the
      hepatotoxicity of chemicals and endotoxin. It has been shown that injection of
      Corynebacterium parvum in rats induces macrophage activation that protects
      against toxic effects of carbon tetrachloride and acetaminophen, five days after
      injection, and this protection is due to inhibition of microsomal oxidizing
      enzymes and increased production of glutathion. To verify if the protective
      effect occurs soon after Kupffer cell activation, with different activators, male
      albino rats were treated with intravenous injection of BCG (0.5 ml with 7.5.10(8)
      bacilli), Corynebacterium parvum (30 mg/kg) or zymosan (7.5.10(6) yeast cells).
      Fourty-eight hours after the injection of one of the macrophage activators, the
      animals and rats treated with intravenous injection of saline (controls) received
      carbon tetrachloride by subcutaneous route (1 ml/kg of CCl4, 3:1 in soybean oil).
      Fourty-eight hours after the animals were killed after ether anesthesia and
      fragments of the liver were fixed, paraffin embedded and the sections stained
      with hematoxylin and eosin. A Weibel grid with 168 points was used to estimate
      the percent volume of necrosis and severe hydropic degeneration. The results
      showed that the volume density of necrosis and severe hydropic degeneration were
      significatively lesser in rats treated with the three Kupffer cells activators.
      The protection was greater with BCG and Corynebacterium parvum than with zymosan.
      These results confirm that activation of Kupffer cell with three different
      activators can induce protection against liver cell injury produced by carbon
      tetrachloride in rats soon as 48 h after injection of activators.

PMID- 9611294
TI  - [Diffuse primary malignant mesothelioma in abdominal cavity].
AB  - Two cases of diffuse malignant mesothelioma of abdominal cavity were analysed.
      These tumors arise from the peritoneum and are also found in the parietal and
      visceral pleura, pericardium and in vaginal tunic. All of them, infra or supra
      diaphragmatic, are associated with asbestos exposure in at least 80% of cases. It
      is difficult to explain how inhaled asbestos induces peritoneal neoplasms. This
      aspects become very important in the diagnostic, basically why it is done at
      laparotomy or laparoscopy. When was proceed the biopsy of the lesions, and
      occasionally by identification of malignant mesothelial cells in ascitic fluid.
      In this two cases exposed considerations about the advanced phase of diagnostic
      are made, the diagnostic was performed in the majority of the collected cells,
      showing the advanced stage of the disease. At that time of diagnosis we observed
      poor evolution. We call attention to the importance of precancer diagnosis, the
      best chance to treatment options, always based on surgical resections, radiation
      or chemotherapy alone or combined. If the radical surgery is not possible, this
      patients must be treated by chemotherapy or radiotherapy, defined after complete
      staging of the disease.

PMID- 9611295
TI  - Synchronous primary malignant lymphoma and carcinoma of the stomach.
AB  - A case of synchronous concurrent carcinoma and primary malignant lymphoma
      developing as two independent tumors of the stomach is presented. The clinical
      and pathological diagnosis and therapeutic problems associated with synchronous
      tumors of the stomach are discussed. A possible relationship between the two
      tumors and the role of Helicobacter pylori are also reviewed.

PMID- 9611296
TI  - [Current concepts of digestion and absorption of carbohydrates].
AB  - The aim of this paper is to review recent aspects of digestion and absorption of
      carbohydrates that are the main source of energy in human diets. Recent
      researches have found that starch is not largely hydrolysed and absorbed in the
      small bowel but one part of it is resistant to digestion. Several food factors
      may be responsible for digestion and absorption velocity and totality of
      carbohydrates. Therefore, carbohydrate classification must be based not only on
      molecular size to express the real carbohydrates utilization as an energy source
      by humans. In agreement with molecular size of carbohydrate, its classification
      can be: a) monosaccharides; b) disaccharides; c) oligosaccharides; d)
      polysaccharides. In agreement with carbohydrate digestibility or availability,
      its classification can be: a) digestible carbohydrates; b) undigestable
      carbohydrates (NSP). Carbohydrate digestibility can be altered by several factors
      like: Intrinsic factors: a) physical structure; b) molecular physical
      distribution; c) physical state of food; d) food antinutrients. Extrinsics
      factors: a) chewing; b) transit time of food; c) amount of starch present; d)
      diet antinutrients. Under influence of this factors, process of digestion happen
      by enzymatic activity a long the gastrointestinal tract. Salivary and pancreatic
      amylase; glycosidases of the duodenal enterocyte brush border (lactase, sacarase
      and maltase), whose activity happen by close interaction of digestive breakdown
      with transport. The summarized pathways of the absorptive process: 1. movement
      from the bulk phase of the lumenal or mucosal fluid to enterocyte surface; 2.
      movement across the brush border membrane through specific transporters: a)
      SGLT1; b) GLUT 5; c) passive diffusion. 3. movement across the basolateral
      membrane by the GLUT 2.

PMID- 9611297
TI  - [Acute diarrhea: stool water loss in hospitalized infants and its correlation
      with etiologic agents and lactose content in the diet].
AB  - Forty weaned male infants were studied during their first year of life, all
      hospitalized with acute diarrhea in the Gastroenterology and Metabolism Unit of
      the Hospital "Umberto I", Sao Paulo, SP, Brazil. We evaluated and quantified
      water fecal losses, employing the metabolic bed technique, relating the feeding
      formula employed with the different causal enteropathogenic agents. 67.5% of the
      studied infants were under six months and 40% under three months of age. Two
      groups were randomly assembled to receive, lactose or lactose free feeding
      formulae. Twenty one patients received a lactose-containing formula (Ninho 10%)
      and the other 19 children were fed caseine (Portagen) formulae. According to
      coproculture results and identification of enteropathogenic agents, we divided
      the studied infants relating feeding formula with the presence or absence of the
      enteropathogenic Escherichia coli (EPEC): I-13 with positive coproculture for
      EPEC and diets which included lactose--(L/EPEC+); II--eight with negative
      coproculture for EPEC and diets which included lactose--(L/EPEC-); III--seven
      with positive coproculture for EPEC and lactose free diets--(G/EPEC+); IV--12
      with negative coproculture for EPEC and lactose free diets. (G/EPEC-). The most
      frequently isolated agent at coproculture was EPEC, in 20 of the cases (50%),
      followed by Campylobacter (7.5%). It was also possible to observe that the
      frequencies of EIEC, Salmonella and Rotavirus were all equal (2.5%). Mixed
      infections occurred only between EPEC and EIEC, registering a frequency of 5%.
      The EIEC samples, associated to EPEC 0111 were serotyped as 0 28 ac: H- and 0
      152:H-. The use of metabolic bed made the evaluation of fecal volumes possible by
      a simple and quick technique, thus allowing a closer clinical monitoring, as well
      as a more reliable evaluation of the patients hospitalized with acute diarrhea.
      Average acceptance volumes of the formulae--either with or without lactose--were
      always below the amount recommended by FAO/WHO (100 kcal/day) which shows the
      impact of acute diarrhea on the decrease of food intake. The average volumes of
      watery fecal losses found among any of the studied subgroups may be considered
      quite relevant when compared to standard values. Especially within the L/EPEC+
      group fecal losses, both on the first day (83.56 ml/kg/day) and, mainly, on the
      second (119.44 ml/kg/day) reached exceedingly high levels indicating a disastrous
      association between the presence of EPEC in the small intestine and lactose offer
      in the diet. Thus, the results show that there exists a positive and significant
      association between poor lactose absorption and the presence of EPEC in the
      feces. WHO's recommendation proposing the use of diluted cow milk, in universal
      and indiscriminate administration, in the two first days of the disease, may
      represent a risk factor, not only for malnutrition, but also for the survival
      rates of children with severe diarrhea, especially those under six months of age
      and hospitalized with EPEC enteroinfection.

PMID- 9611298
TI  - [Dermatoglyphic patterns in celiac disease].
AB  - In 1990 a project was performed in Israel in which the authors reported a higher
      frequency of whorls and a lower frequency of ulnar loops in the dermatoglyphic
      pattern of children with celiac disease than in children belonging to control
      group. Based on these findings we carried out a similar study with our local
      population. Thirty six celiac children, their parents and siblings had their
      fingerprints analysed and compared to a control group matching for age, sex and
      race, in order to assess the efficiency of this method for the diagnosis of
      celiac disease. A statistically significant higher frequency of whorls and arches
      was found in celiac children than in control group (whorls = 40.6%, arches =
      11.7%; whorls = 30.3%, arches = 5.0%, respectively) as well as a strong
      correlation between the dermatoglyphic pattern of the parents and their celiac
      children. There was also a statistically higher frequency of whorls > = 4 in
      celiac children (55.6%) than in controls (30.6%). The conclusion is that the
      dermatoglyphic pattern analysis can be used as a complementary data. Due to its
      low sensitivity (55.6%) and specificity (69.4%) considering the presence of four
      or more whorls, it is not useful as a screening or as a method itself, for the
      diagnosis of celiac disease.

PMID- 9611299
TI  - Lysenkoism and the population control movement.
AB  - The case of Lysenkoism in the Soviet Union helps us understand how people's wrong
      beliefs can be influenced by what the information they receive from outside,
      especially when there is a large volume of media coverage and there is no
      contrary information to be heard. The population control movement in contemporary
      United States has many parallels to the Lysenko episode.

PMID- 9611300
TI  - [Information on the use of laboratory animals indicated in scientific articles].
AB  - A sample of 15 Costa Rican scientific papers published since 1985 reported only
      49% of the necessary information about laboratory animals and experimental
      conditions, slightly better than in the rest of Latin America (47%, sample = 15
      papers) but lower than in the USA and Europe (60%, sample = 15). Adequate
      information on laboratory animals use for biomedical research is important to
      standardize their use.

PMID- 9611301
TI  - Occurrence of citrus viroids in Costa Rica.
AB  - A survey for citrus viroids was conducted in the major citrus commercial growing
      areas in Costa Rica. Screening of 36 sweet orange and 12 lemon trees resulted in
      the detection of members of four of the five citrus viroid groups as determined
      by nucleic acid hybridization using specific RNA probes and polymerase chain
      reaction (PCR) using specific oligonucleotide primers. CEVd, CVd-IIa, CVD-IIb and
      CVd-III viroids were found to be widespread in the three main regions of
      commercial citrus production. CVd-Ib was only found in lemon in Nicoya.

PMID- 9611302
TI  - Rotavirus and coronavirus outbreak: etiology of annual diarrhea in Costa Rican
      children.
AB  - In Costa Rica, an annual outbreak of infant diarrheal disease (December and
      January) was reported since 1976, and rotavirus was incriminated later as the
      main etiological agent (1976-1981). Apparently the disease has not been
      systematically studied in Costa Rica after 1981. For that reason the occurrence
      of the outbreak was retrospectively documented for 1993-1995 and etiology was
      studied in 48 children treated for diarrhea at the Nacional Children Hospital
      (capital city of San Jose) during December, 1994 and January, 1995. Rotavirus
      (33%) and coronavirus (27%) were the main agents. To our knowledge, this is the
      first time that these viruses are incriminated in an outbreak of diarrhea.

PMID- 9611303
TI  - [Heparin-induced thrombocytopenia. Diagnosis, clinical course and therapeutic
      alternatives].
AB  - Heparins are common and have been widely used in prophylaxis and therapy of
      thromboembolic disorders for many years. Nevertheless, the serious side effect of
      heparin-induced thrombocytopenia type II (HIT II) has attracted attention only
      recently. First evidence of HIT II is a drop in platelet count below 100,000/mm3.
      Subsequently, thromboembolic complications occur 6-20 days after beginning
      heparin therapy. Overall mortality is 20-30% of patients with HIT II. Therefore,
      frequent platelet counts are required for early diagnosis. However, in cases of
      moderate or absent thrombocytopenia the diagnosis of HIT II can be difficult.
      Laboratory tests such as heparin-induced platelet activation (HIPA) test or
      heparin/PF4-antibody-ELISA have limited sensitivity and specificity. Therefore,
      with typical clinical findings, divergent laboratory results should be
      interpreted with caution. If HIT II is suspected, all heparins should be
      discontinued immediately. Due to a high cross reactivity rate with the heparin
      dependent antibody, subsequent therapy with low molecular weight heparins (LMWH)
      is contraindicated. As treatment of choice danaparoid or recombinant hirudin may
      be administered. Oral anticoagulation should be started cautiously with an
      alternative immediate-acting antithrombotic agent. More widespread use of LMWH
      may reduce the incidence of HIT II in the future. Nevertheless, the main and most
      important factor in the prevention of this life-threatening complication is the
      awareness and caution of the clinician.

PMID- 9611304
TI  - [The motivation to use complementary medicine healing methods. Study of a general
      internal medicine and orthopedic patient sample].
AB  - 436 patients from two different clinics of internal medicine and one orthopaedic
      unit were asked to fill a questionnaire on their attitude towards and use of
      alternative medicine. Of the 272 questionnaires returned, 235 could be used for
      analysis. 42.6% of all analysed persons confirmed use of alternative medicine.
      About half of them were motivated to do so by their nursing staff. Homeopathy was
      by far the most frequently used method. Persons who used alternative medicine
      were characterised by a distinct environmental awareness and regular sports
      activity. They had also often had positive experience of alternative methods in
      childhood. On the other hand, age, sex, education, duration of the treated
      disease and success of conventional therapy did not correlate significantly with
      the use of alternative medicine. An essential motive for the need to seek help by
      alternative therapists was the opinion that conventional forms of treatment would
      concentrate too much on the purely physical side of a health problem. All in all,
      users of alternative medicine did not seek confrontation with conventional
      medicine but rather sought a real complement to conventional forms of treatment.

PMID- 9611305
TI  - [Chronic giardiasis with intestinal dwarfism and delayed puberty in
      immunoglobulin deficiency syndrome: complete catch-up growth after therapy].
AB  - A 10-year-old, previously healthy Swiss boy suffered from repeated episodes of
      watery diarrhea for some months following a summer camp holiday. No etiology was
      found, and except for symptomatic treatment no other therapy was necessary. Five
      years later he was investigated because of growth failure, with a bone age of
      11.5 years, but the correct diagnosis was not established. Only when he was
      reinvestigated at the age of 20 years, because of persistent growth failure and a
      bone age of 14 years, were Giardia lamblia trophozoites seen microscopically on
      the surface of duodenal mucosa biopsy specimens. At the same time
      dysgammaglobulinemia was detected which may have predisposed the gastrointestinal
      tract to chronic giardiasis. After a 10-day course of metronidazole the patient
      experienced catch-up growth and completed his pubertal development. The
      dysgammaglobulinemia persisted after therapy. This case showed that in patients
      with intestinal growth failure, catch-up growth and completion of pubertal
      development are possible even after the age of 20 years if nutritional supply is
      sufficient. Bone age determinations serve to indicate remaining growth potential.

PMID- 9611306
TI  - [Cancer and the cell cycle: a current merry-go-round in oncology of clinical
      relevance].
AB  - In normal cells the cell cycle, cell proliferation and differentiation are
      precisely regulated by a variety of different players. These include cyclins,
      which help to drive cells into mitosis, as well as cyclin-dependent kinase
      inhibitors which may be viewed as cell cycle brakes. Alterations in such genes
      and their products are frequent in human cancer. Overexpression of cyclins has
      been identified in lymphoma and in non-small cell lung cancer. Mutations in
      cyclin-dependent kinase inhibitors, such as the p16 gene, are particularly
      frequent in human cancer cell lines. Tumor suppressor genes, including the
      retinoblastoma gene and the p53 gene, are also crucial in this context, and their
      inactivation through gene mutations in cancer is frequent. Assessing alterations
      of genes associated with cell cycle regulation in malignancy or their protein
      products is of clinical interest. Molecular and immunological techniques to
      identify such alterations may provide unique markers of prognostic and predictive
      value in cancer. In addition, the technology is being developed for the treatment
      of such genetic alteration in cancer cells at the molecular-genetic level.
      Protocols introducing the wild-type p53 gene in tumors with p53 inactivations are
      on the way and clinical trials, although very preliminary, seem to be opening up
      completely new avenues for cancer treatment. Investigating cell cycle alterations
      in cancer is no longer the exclusive province of experimental research, but has
      rapidly developed into an area of unique clinical relevance.

PMID- 9611307
TI  - [Should the presence of coiled blood flow in the left heart ventricle and aorta
      be taken into consideration when constructing artificial heart valves?].
AB  - The use of an original device developed by the authors which was introduced in
      the blood flow in experiments in dogs has confirmed the presence of coiled blood
      flow in different parts of the aorta. The rate, direction and angle of coiling
      were calculated. The results obtained suggest that the fact of coiling the blood
      flow should be taken into account when constructing new models of artificial
      valves of the heart in order to decrease the energy value of the cardiac output,
      to prevent injury of the formed elements of blood and thrombogenesis.

PMID- 9611308
TI  - [Congenital bronchoesophageal fistulas].
AB  - During the period from 1970 till 1996 six patients with congenital
      bronchoesophageal fistulas were operated upon which was 0.75% of all
      developmental defects of the lungs. The leading symptoms of bronchoesophageal
      fistulas in the clinical picture are cough during and after meals and discharge
      of food mass with sputum. Roentgeno-endoscopic examinations are thought to be the
      main diagnostic method. Radical treatment of patients with the respiratory
      esophageal fistulas was facilitated by dissection of the fistula passage and
      closure of the openings in the esophagus and bronchus, covering the suture line
      on the esophagus with a flap of the mediastinal pleura, pericardium. The
      irreversible alterations in the lung tissue require a one-stage operation on the
      lung. Palliative operations (gastrostomy, jejunostomy) are indicated in severe
      pyo-destructive alterations in the lungs for preparation to radical operation.

PMID- 9611309
TI  - [Surgical correction of vertical reflux of blood in musculo-venous pump of the
      lower limbs and pelvis in patients with varicose veins].
AB  - The authors have made an analysis of results of treatment of 469 patients with
      the varicose disease. During operations on them surgical correction of vertical
      reflux of blood was performed by means of extravasal correction of incompetent
      valves of the femoral, popliteal and tibial veins, resection or obturation of the
      posterior tibial veins. Traditional methods (frame spiral and fascioplication)
      and original ones (three ligatures and tension of the valve cusps through the
      frame spiral coil) were used. Elimination of the vertical reflux of blood in each
      of the four pumps (abdomino-caval and femoral ones, those of the leg and foot)
      forming the musculo-venous pump, results in getting 7% greater amount of
      excellent and good results, bad results were obtained in 3.4% less number of
      cases. The period of temporary loss of working ability becomes shorter.

PMID- 9611310
TI  - [A comparative assessment of the effectiveness of dearterialization of the liver
      and intraorgan chemotherapy in patients with liver cancer].
AB  - An experience with treatment of 90 patients with primary (42) and metastatic (48)
      carcinomas of the liver who were treated by ligation of the hepatic artery (in 24
      patients), embolisation of the hepatic artery (in 21 patients) in combination
      with intraarterial and intraportal chemotherapy or without it is analyzed. It has
      been shown that these methods are more effective in metastatic carcinoma of the
      liver, longer terms of life of the patients were obtained when dearterialization
      of the liver was combined with chemotherapy.

PMID- 9611311
TI  - [Characteristics of the use of laparoscopic cholecystectomy in middle-aged and
      aged patients].
AB  - Under analysis are results of using laparoscopic cholecystectomy (LChE) in 43
      elderly and senile patients (from 60 to 88 years of age). The control group
      consisted of 67 patients of young and middle-aged patients (from 25 to 59 years
      of age) operated upon by the same method. Based on a comparative analysis of 2
      groups of patients the authors have established age-dependent specificity of
      using LChE at all stages of treatment from the preoperative preparation and
      choice of indications for operation till discharge from the hospital. The
      materials presented show that most of non-standard difficult and complicated LChE
      take place just in the age older than 60. When performing LChE in such patients
      additional intraoperative technical means should be used and the indications for
      laparotomy must be wider. A conclusion is made that when estimating results of
      LChE it is expedient to analyze results of treatment of elderly and senile
      patients by this method.

PMID- 9611312
TI  - [End-to-end anastomosis as a method of choice in right hemicolectomy].
AB  - The newest and long-term results of treatment of 239 patients were analyzed in
      whom right hemicolectomy with ileotransverse anastomoses "end-to side", "side-to
      side" and "end-to-end" were fulfilled. When estimating the results, the data of
      original methods developed and tested in the clinic were used for studying the
      motility and bioelectrical activity of the intestine in addition to clinical
      parameters. The main regularities of the development of postoperative
      complications were found in randomized groups. It was established that choice of
      the optimum variant of the anastomosis in right hemicolectomy was dependent on
      the understanding of pathophysiological consequences of either intestinal
      anastomosis. The anastomosis "end-to-end" is the quickest to fulfil, less
      traumatic and safe of the 3 types of ileotransverse anastomosis.

PMID- 9611313
TI  - [Enteral correction of hemodynamics in massive hemorrhage].
AB  - The method of enteral correction was clinically studied in complex treatment of
      20 patients with massive blood loss. An especially elaborated solution identical
      in its composition to chyme was used for the intravenous infusion. Mafusol was
      used for anti-ischemic defense of the intestine. The intestinal therapy at the
      early postoperative period allows effective elimination of hypovolemia,
      stabilization of the central hemodynamics indices, the earlier reestablishment of
      functional activity of the gastrointestinal tract. The enteral correction results
      in 30% less total volume of the intravenous infusion therapy and less amount of
      complications resulting from it.

PMID- 9611314
TI  - [Ways of improving treatment of patients with abdominal gunshot wounds].
AB  - Results of relaparotomies in 219 wounded with gunshot abdominal wounds got in
      local wars were analyzed. The main causes of relaparotomies were diagnostical,
      tactical and technical errors made during primary operations. The final outcome
      of the treatment depends upon the terms and volume of reoperations. Favourable
      results were frequent often in performing the programmed sanitation of the
      abdominal cavity which should be fulfilled in cases of diffuse peritonitis. The
      elaborated method of early diagnosis of postoperative complications, use of
      programmed sanitation of the abdominal cavity and restricted volume of
      reoperations allowed the frequency of relaparotomies to be decreased from 14.8 to
      12.1% and lethality after them from 53.2 to 25%.

PMID- 9611315
TI  - [Errors and complications in the treatment of gunshot thoracic injuries].

PMID- 9611316
TI  - [Prevention of errors and complications of laparoscopic cholecystectomy].
AB  - Great experience with performing laparoscopic cholecystectomies enabled the
      authors to work out a classification of failures, errors and complications
      appearing during preparation, in the process or after such operative
      interventions. Recommendations are given on prevention of them and for their less
      frequency.

PMID- 9611317
TI  - [Causes of lethal outcome in acute adhesive intestinal obstruction].
AB  - Causes of 90 lethal outcomes from acute intestinal obstruction were analyzed.
      Among them diagnostic errors were made in 10% of cases, late admission to the
      hospital and prolonged conservative treatment resulted in death in 37.8%,
      operative and postoperative complications--in 52.2%. A complex system of measures
      is proposed to reduce lethality of patients with this disease including all the
      stages of diagnosis and treatment.

PMID- 9611318
TI  - [Hemostatic therapy of gastroduodenal hemorrhage of non-ulcer genesis by the use
      of reserve mechanisms of hemostasis].
AB  - The article presents summarized results of treatment and examinations of 216
      patients with gastro-intestinal bleedings due to acute errosive hemorrhagic
      gastritis and gastroduodenitis, cancer and polyposis of the stomach, liver
      cirrhosis and portal hypertension, hemorrhage against the background of
      atherosclerosis and arterial hypertension by administration of hemostatic
      medicine into the lymphatic system for activation and reinforcement of the
      reserve monocyte-macrophage mechanism of hemocoagulation. The results obtained
      confirm the expedience of this method of influencing the monocyte-macrophage
      hemostasis, having no complications and giving better medical effects.

PMID- 9611319
TI  - [Premedication with different groups of hypotensive drugs in preparation of
      patients with concomitant arterial hypertension to planned surgical treatment].
AB  - Investigation of hemodynamic changes in 180 women liable to operations of
      supravaginal amputation were carried out in order to chose the optimum method of
      curative premedication in patients with essential arterial hypertension. The
      results obtained show that Adalat in dosage 60 mg daily during 7 days is most
      effective in cases with concomitant border-line hypertension. Anaprilin in dosage
      160 mg daily and Adalat in dosage 60 mg/day during 7 days have the best
      hypotensive effect at the first stage of essential hypertension. Clopheline in
      dosage 300 mg/day or Adalat in dosage 60 mg/day during 7 days are most expedient
      in the course of hypotensive preparing the patients with the II stage of
      essential hypertension.

PMID- 9611320
TI  - [150 years of the use of ether anesthesia in Russia].

PMID- 9611321
TI  - [A new method of angioscopy without exclusion of the vessel from blood
      circulation].

PMID- 9611322
TI  - [Diagnosis and removal of foreign bodies of the trachea and bronchi].
AB  - The article presents results of examination and treatment of patients with
      foreign bodies in the tracheobronchial tree. It was noted that clinical
      manifestations were not leading in diagnosis of aspirated foreign bodies. The X
      ray diagnosis is also not sufficiently effective, especially in cases with
      organic foreign bodies. Fiber bronchoscopy was used in 45 patients for diagnosis
      and removal of foreign bodies from the tracheobronchial tree. Practical
      recommendations are given on the method of removal of the foreign bodies
      depending on the shape, size and kind of the foreign body. The authors consider
      that the main criterion for fulfilling diagnostic fiber bronchoscopy in cases of
      suspected foreign body is information from the patient of probable aspiration of
      a foreign body. High efficiency of both diagnostic and curative fiber
      bronchoscopy for foreign bodies in the tracheobronchial tree is noted.

PMID- 9611323
TI  - [Acute appendicitis in patients with salmonellosis and dysentery].
AB  - Results of 214 appendectomies in patients with acute intestinal diseases were
      analyzed. The clinical course and results of treatment of acute appendicitis
      against the background of salmonellosis and dysentery were discussed. It was
      shown that the theory of infectious nature of acute appendicitis is rightful and
      that valuable etiotropic therapy is necessary for prevention of chronicity of the
      intestinal infection.

PMID- 9611325
TI  - [Gastric neurinoma complicated by hemorrhage].

PMID- 9611324
TI  - [Selective intra-arterial use of small doses of thienam and vasaprostanin the
      treatment of suppurative diseases of the foot in patients with diabetes
      mellitus].
AB  - The authors present data of using the selective intraarterial infusion of Thienam
      and Vasaprostan for treatment of purulent diseases of the foot in 70 patients
      with diabetes mellitus. The microsurgical method was used. The proposed method is
      thought to be expedient and highly effective.

PMID- 9611326
TI  - [Rare localization of duodenal ulcer].

PMID- 9611327
TI  - [Association of perforated ulcer of the duodenal bulb with gangrenous
      appendicitis and phlegmon of Meckel's diverticulum].

PMID- 9611328
TI  - [Cystic dilatation of the common bile duct].

PMID- 9611329
TI  - [Successful treatment of pancreatic pseudocyst in a child with transcutaneous
      drainage under ultrasound control].

PMID- 9611330
TI  - [A case of neglected colonic invagination with rectal prolapse of invaginate and
      strangulation in the anal canal].

PMID- 9611331
TI  - [Successful treatment of knife injury of the abdominal aorta].

PMID- 9611332
TI  - [Infection in surgery. An old problem on the eve of the new millenium. I].

PMID- 9611333
TI  - [Once more on terminology of radical surgery of the rectum].

PMID- 9611334
TI  - [Active methods of teaching surgery to students].

PMID- 9611335
TI  - [Cancer, immunity, immune rehabilitation (according to materials of the 3d
      International Congress on Immune Rehabilitation and Rehabilitation in Medicine.
      Eilat, Israel, May 4-7, 1997)].

PMID- 9611336
TI  - [Possibilities of radionuclide methods of investigation in the diagnosis of
      intracardiac foci of infection].

PMID- 9611337
TI  - [Present-day approach to the diagnosis of hiatal hernia].

PMID- 9611338
TI  - [Laparoscopic cholecystectomy and choledocholithiasis].

PMID- 9611339
TI  - [Quality improvement as global challenge: learning from differences and
      similarities].

PMID- 9611340
TI  - [Polyneuropathy in the critically ill patient--critical illness polyneuropathy].
AB  - Polyneuropathy developing in critically ill patients ("critical illness
      polyneuropathy"--CIP) is diagnosed with increasing frequency in intensive care
      units. CIP is an axonal polyneuropathy leading to difficulties in weaning from
      artificial ventilation and symmetrical flaccid tetraparesis. Pathogenetically CIP
      is considered to be part of the multiple organ dysfunction syndrome (MODS) in the
      course of sepsis or systemic inflammatory response syndrome (SIRS). The incidence
      of CIP in septic patients with MODS ranges from 50% to 70%. Electroneurography
      (ENG) and electromyography (EMG) are essential diagnostic procedures. The
      mortality in patients with CIP is higher than in patients without CIP. Depending
      on the severity of CIP, recovery of neurological function in survivors is usually
      relatively good.

PMID- 9611341
TI  - [Neurological and psychosocial sequelae 4 and 8 years after severe craniocerebral
      injury: a catamnestic study].
AB  - Thirty-three patients (29 male, 4 male) were examined 4 and 8 years after severe
      head injury. The patients underwent a detailed neurological examination. A
      semistructured interview according to the Glasgow Assessment Schedule was
      administered to the patients and their relatives. Most frequent neurological
      features were motor deficits (55%, at both follow-up investigations, mostly
      monoparesis), dysarthria (39% versus 33%), ataxia (49% versus 39%) and anosmia
      (46% versus 33%) at 4 and 8 years, respectively. There was a slight, but not
      significant improvement between the 2 examinations with respect to frequency and
      severity of neurological impairment. There was no significant improvement in the
      activities of daily living and 18% remained totally dependent on other people's
      help. At both follow-ups 85% complained of memory deficits. 67% and 70%
      respectively, suffered from poor initiative and increasing irritability at the
      first and second examination. The patients were more socially isolated and more
      irritable at the second follow-up. Only 12% and 18%, respectively held the same
      job as they had had before the injury; nearly half of them had retired.
      Occupational and psychosocial reintegration appeared to be rather poor in many
      patients. Excessive alcohol intake prior to trauma was identified as a person
      related predictive factor. In contrast to other studies we found persistent,
      although slight neurological deficits. In the long-term, a combination of
      neurological and neuropsychological deficits seems to contribute to residual
      handicap.

PMID- 9611342
TI  - Results of the treatment of colorectal cancer complicated by obstruction.
AB  - 654 patients with colorectal cancer were operated on during the period 1982-1993.
      Acute surgical intervention was performed in 232 cases because of large bowel
      obstruction, whereby the obstruction tumor was localized in the colon in 160
      patients and in the rectum in the remaining 72 patients. 53 of the patients were
      designated as stage T3,4N-M0 stage, 97 as T3,4N+M0 and 82 as T3,4N+/-M1.
      Histologically, well- and moderately-differentiated adenocarcinoma was diagnosed
      in 69%, poorly differentiated and mucinous adenocarcinoma in 29% and squamous
      cancer in 2% of the cases. The patients were distributed in 4 groups according to
      the clinical presentation of the obstruction: acute (n = 60), subacute (n = 52),
      recurring (n = 42) and chronic (n = 78) forms. 122 radical and 110 palliative
      operations were performed. 34% of the patients had postoperative complications.
      The overall postoperative mortality was 25% AND it was highest in one-stage
      operation with a primary anastomosis (p < 0.05). The 5-year survival in patients
      with obstructive colon and rectal tumours was 32% and 27%, respectively (p =
      0.631). The patients with differentiated adenocarcinoma have a better prognosis,
      as well as those without regional lymph node metastases (p < 0.05). The patients
      without obstruction operated on during the same period, had a higher 5-year
      survival for both colon (p < 0.01) and rectal (p < 0.0019) cancer.

PMID- 9611343
TI  - [Risk and procedure education in anesthesiology. Overview of Austrian and German
      legal regulations].
AB  - Informed consent is currently an ethical, medical and legal requirement. An
      increase in public discussion of real or supposed malpractice has led to critical
      attitude in patients and increased demands on informed consent by the courts.
      Unfortunately, the legal requirements of informed consent have developed from
      atypical situations involving dissatisfied and injured patients rather than from
      the more usual occurrences of physicians helping patients with subsequent patient
      satisfaction. In addition, laws have not set forth clear guidelines for
      physicians to follow. We review the elements of informed consent based on current
      Austrian and German jurisdiction in the particular field of anesthesiology and
      summarize the legal and medical realities in order to point out specific criteria
      for decision making.

PMID- 9611344
TI  - [Bovine spongiform encephalopathy and Creutzfeldt-Jakob disease].

PMID- 9611345
TI  - [Transmissible spongiform encephalopathies (prion diseases)--molecular principles
      and in vitro models].
AB  - Prion diseases are rare neurodegenerative and transmissible diseases affecting
      humans and mammals. The infectious agent of these deadly disease has been termed
      prion since in many respects this agent behaves differently from viruses. The
      prion hypothesis which was put forth by Stanley Prusiner in 1982 holds that the
      infectious agent consists of a conformationally changed normal cellular protein
      (PrPC). PrPC is a copper-binding protein of yet unknown function. PrPSc (the
      conformationally changed protein) in addition to its association with infectivity
      seems to have neurotoxic properties which are mediated by microglia in the CNS.
      Future research will have to concentrate on the dynamics of the conformational
      change from PrPC to PrPSc and understanding the neurotoxic mechanisms in prion
      diseases.

PMID- 9611346
TI  - [Significance of prion protein in transmission of prions and in pathogenesis of
      spongiform encephalopathies].
AB  - Prion disease or transmissible spongiform encephalopathies are caused by novel
      pathogens termed prions. Unlike classical infectious agents such as viruses or
      bacteria, prions lack an independent genome and consist largely if not entirely
      of an abnormal form of the host-encoded prion protein. How prions multiply is not
      known. A wealth of experimental evidence supports an essential role for the host
      encoded prion protein in susceptibility and pathogenesis of prion diseases and in
      the propagation and spread of prions. In addition, B lymphocytes have been found
      to play a crucial role in the neuroinvasiveness of prions.

PMID- 9611347
TI  - [Transmissible spongiform encephalopathies in animals].
AB  - Transmissible spongiform encephalopathies in animals are known for centuries. In
      particular scrapie in sheep and goats occurs worldwide; it spreads as a natural
      disease and is genetically controlled. Chronic wasting disease (CWD) in the
      United States (Wyoming and Colorado) also spreads as natural disease among free
      ranging and captive elk and mule deer. In contrast, transmissible mink
      encephalopathy (TME) of mink in fur producing farms is caused by contaminated
      feed; the source of this food contamination is still controversial. The only
      occurrence of a TSE in an avian species was reported from a flock of ostriches in
      a German zoo. The origin of the outbreak of bovine spongiform encephalopathy
      (BSE) in Great Britain could be traced back to feeding concentrates containing
      animal proteins contaminated with the agent of sheep scrapie. BSE was introduced
      into other countries, e.g. Switzerland and France, through the import of
      contaminated feeds from Great Britain. In addition, sporadic cases of TSE
      occurred in 10 other species, in particular domestic cats and zoo animals, e.g.
      antelopes and large cats. The diagnosis is based on the neuropathological
      examination of the brain as well as the demonstration of the disease specific
      protease resistant prion protein (PrPres). The first measures against the disease
      aim at eliminating the risk factors. The most important is the prohibition of
      feeding animal protein concentrates to ruminants. Thanks to this measure the
      incidence of BSE diminished remarkably. To protect consumers of beef products, in
      countries with BSE the potentially infectious organs of all cattle are
      confiscated at slaughter. Yet, in Great Britain this measure was introduced only
      at a point of time when BSE had already spread all over the country. Therefore,
      there is a strong probability of an exposition of consumers of beef with the BSE
      agent, which might have caused the new variant of Creutzfeldt-Jakob disease
      (nvCJD).

PMID- 9611348
TI  - [Transmissible spongiform encephalopathies--illnesses in the human].
AB  - Transmissible spongiform encephalopathies (TSEs) or prion diseases in man and
      animals are of utmost interest at present. Reasons are the highly probable origin
      from BSE of a new variant of Creutzfeldt-Jakob disease (CJD) in the UK and
      France, the new paradigm in biomedicine of the association of heredity and
      transmissibility, and the possible propagation of infectivity by protein only
      according to the prion hypothesis. Determination of the 14-3-3 protein in CSF and
      magnetic resonance imaging are promising new diagnostic tools; however, clinical
      examination yields only a suspect diagnosis, with formal criteria for "probable"
      or "possible" CJD. Definite diagnosis relies on neuropathology at autopsy or, in
      rare instances, brain biopsy. Handling of laboratory material from TSE patients
      requires specific measures of precaution and decontamination. Although blood and
      blood products have been shown to transmit disease, experimental and
      epidemiologic data for disease transmission via blood transfusion are lacking.
      New WHO regulations define exclusion criteria for blood donors. A special
      situation applies to the UK because the distribution of infectivity in the new
      CJD variant might differ from that of classical TSEs; therefore leukodepletion of
      blood donations was recommended.

PMID- 9611349
TI  - [Cerebrospinal fluid diagnosis of Creutzfeldt-Jakob disease].
AB  - Diagnosis of Creutzfeldt-Jakob disease (CJD) at lifetime according to the
      international diagnostic criteria may be greatly improved by the additional assay
      of 14-3-3 protein in cerebrospinal fluid (CSF). Occurrence of 14-3-3 protein in
      CSF may be observed in etiologically different conditions of brain damage, but
      confers high diagnostic specificity in cases of suspected CJD based on the
      diagnostic criteria. We investigated the occurrence of 14-3-3 protein in CSF of
      20 patients with an accompanying diagnosis "suspected CJD", of whom 5 cases had
      to be classified as neither probable nor possible CJD according to the
      international diagnostic criteria, as well as in 18 control cases with diseases
      other than CJD. Assay of 14-3-3 comprised SDS-PAGE, western blot, immunostaining
      with specific antibody, and luminiscence detection. With regard to case histories
      at the end of our study, 8 definitive and probable CJD cases were 14-3-3 positive
      and 2 possible CJD cases 14-3-3 negative. Of the 10 cases with final diagnosis
      other than CJD, 8 cases (in part with manifest or suspected brain damage; one
      case with hemorrhagic CSF) were 14-3-3 positive. Of the 18 controls with diseases
      other than CJD, 6 patients, characterized by brain tissue lesions or meningitis,
      respectively, were found to be 14-3-3 positive. Our observations, the first in
      Austria and on a limited number of patients yet, are in accordance with previous
      reports in the literature and further support the use of the 14-3-3 protein assay
      in CSF as a diagnostic tool for CJD, provided that probands had been pre
      evaluated positively by the international diagnostic criteria for CJD.

PMID- 9611350
TI  - [Epidemiology of transmissible spongiform encephalopathies (prion diseases) in
      Austria].
AB  - Between 1969 and 1996, transmissible spongiform encephalopathy was definitely
      diagnosed by autopsy and/or biopsy in 98 Austrian patients. The yearly incidence
      increased significantly in past years (1996: 1.41 cases per million inhabitants).
      This increase likely results from increased awareness in the medical community
      and effectuation of the diagnostic autopsy. The new variant of Creutzfeldt-Jakob
      disease (CJD), probably transmitted from bovine spongiform encephalopathy (BSE),
      has not occurred in Austria. The percentage of patients older than 70 years
      increased until 1989 and declined slightly thereafter. One patient received a
      dura mater graft 11 years before death. Another patient had familial CJD with a
      glutamatelysin mutation on codon 200 of the prion protein (PrP) gene PRNP. One
      more patient died from Gerstmann-Straussler-Scheinker disease (GSS), three
      patients from fatal familial insomnia (FFI). Another patient received
      intramuscular injections of a purified RNA preparation (Regeneresen) produced
      from various organs including brain. The age at death symmetrically distributes
      around a median of 64 years. Two CJD patients were unusually young (27 and 30
      years). Most patients (72.7%) died within 6 months of disease. Retrospectively,
      81% of patients had clinical diagnostic criteria of probable or possible CJD (52%
      probably and 29% possible). In 19%, clinical criteria for CJD were not fully met.
      There is no case clustering with specific professional groups or geographic
      areas. However, residents of Vienna, or Vienna and Lower Austria, respectively,
      had CJD diagnosed twice or three times more frequently than the rest of the
      country, indicating regionally differing qualities of case retrieval.

PMID- 9611351
TI  - [Complete radical prostatectomy and positive lymph nodes (stages pT1 to 4, N1 to
      3, M0, D1)].
AB  - Lymph node metastases are rarely detected during radical prostatectomy (55/647
      patients in our series or 8.5%) and several authors consider that lymphadenectomy
      is unnecessary in most cases. Criteria based on clinical stage, PSA and tumor
      grade have been elaborated in order to avoid pelvic lymph node dissection in a
      low risk population. It is commonly admitted that patients with clinically
      localized prostate cancer, a PSA level < 10 ng/ml, and a Gleason score < 7 could
      be spared a pelvic lymphadenectomy. In our series, these patients account for 12%
      of positive nodes. The best treatment for prostate cancer patients with a nodal
      disease is controversial. We compare the evolution of two groups of patients:
      radical prostatectomy alone or combined with an immediate adjuvant hormonal
      treatment. We observe a difference between the two groups for biological
      progression (PSA failure) but not yet for clinical progression nor for survival
      as our mean follow-up in only 6 years.

PMID- 9611352
TI  - [Correction of severe median hypospadias. Review of 77 cases treated by the onlay
      island flap technic].
AB  - Seventy-seven hypospadias, selected from a series of 504 treated in our
      institution, were operated using the pediculated transverse "onlay" preputial
      graft. We try to demonstrate that this technique produces excellent functional
      and cosmetic results. Chordee can be corrected using extensive dissection of the
      urethral plate with association, if necessary, of a Nesbit type of dorsal
      plication. Complications rate, in our hands, is lower in comparison to the
      technique described by John Duckett, where the urethral plate is divided and a
      complete urethral tube is performed. We report 4 fistulas, one distal end
      breakdown of the repair and one postoperative hematoma that had to be revised.
      Because of this low complication rate, in many cases, the "onlay" pediculated
      graft replaces advantageously the Duckett type of repair.

PMID- 9611353
TI  - [Methodology of penile isotope imaging. Evaluation].
AB  - AIMS: Duplex ultrasonography and pulsed doppler analysis or dynamic infusion
      cavernosometry and cavernosography are used for functional evaluation of penile
      arterial or venous dynamics during a pharmacological erection. The accuracy of
      the echographic investigations is correlated to the investigator experience.
      Cavernosometry and cavernosography are more invasive technique than the
      radioisotope erection penogram, which is a reproductive and reliable test.
      MATERIAL AND METHODS: We investigate 60 patients. Neurological, psychological and
      endocrinological etiology are excluded. The technique is described: thyroid is
      blocked by potassium perchlorate, bloodpool is labelled with Tc99m, a dynamic
      study is performed over 60 mn with intracavernous injection of PGE1 5g or
      Papaverine 30 mg at T10mn, ROIS are defined by computer processing, a phalogram
      curve is provided. RESULTS: This noninvasive test sorts out arteriogenic,
      venogenic and psychogenic impotence by a qualitative curve analysis. The
      quantitative parameters depending on numerous time consuming variables have
      proved to be of poor clinical use and non significant. We objectivate 20
      psychogenic impotence, 27 arteriogenic impotence, 7 venous leakage and 6 mixed
      (arteriogenic and venogenic) impotence. Statistic evaluation of arteriogenic
      lesions comparative by doppler technique reveals a sensitivity of 83% and a
      specificity of 87%. The advantages of the test are; ambulatory, objective,
      noninvasive and reliable investigation. In the same time, "qualitative" data
      evaluates the response to a pharmacological induced erection. CONCLUSIONS: The
      radioisotope erection penogram is a noninvasive, reproductive and reliable
      screening test for vasculogenic impotence.

PMID- 9611354
TI  - Prostatic fluid and sperm examination: 106 cases. Preliminary study on
      infertility.
AB  - OBJECTIVE: This research is designed to explore the relationship between the
      results of routine prostatic fluid and sperm examination obtained from 106
      married male young people. METHODS: The subject of the present research included
      106 married young men who underwent pre-martial checkups. Leukocyte count, pH
      value, and lecithin body in prostatic fluid were measured and compared with the
      data of sperm examination. RESULTS: The results showed that when leukocyte count
      in prostatic fluid was over 10/HPF, the survival rate of sperms decreased
      significantly, liquefying time prolonged significantly (p < 0.001), sperms
      decreased in number from 54.42 million/mm3 to 38.93 million/mm3 with rise in pH
      value. CONCLUSIONS: Our research reveals a positive correlation between increased
      leukocytes in prostatic fluid and infertility.

PMID- 9611355
TI  - Fracture of the penis: role of ultrasonography in localizing the cavernosal tear.
AB  - Fracture of the penis is a rare surgical emergency. A case is presented where a
      7.5 mHz ultrasonography probe was used to demonstrate the tear in the corpus
      cavernosum. Ultrasonography was able to identify the site and extent of the
      injury. Preoperative ultrasonography shows the best place for surgical incision
      and can be used to avoid negative surgical exploration.

PMID- 9611356
TI  - Angiokeratoma: a cause of scrotal bleeding.
AB  - We report a case of Fordyce angiokeratoma which presented with bleeding from the
      scrotum. The difference between Fordyce's angiokeratoma and Fabry's angiokeratoma
      corporis diffusum is described. The diagnosis, treatment and prognosis of scrotal
      angiokeratoma are discussed.

PMID- 9611357
TI  - [Reiter syndrome: apropos of a case].
AB  - We report the case of a 25 year-old man presenting Reiter's syndrome (urethritis,
      conjunctivitis and oligoarthritis). This clinical triad is a particular
      expression of reactive arthritis. A genital or enteric infection can be
      responsible for the onset. Presence of HLA B27 histocompatibility antigen is a
      genetic factor favoring the development of Reiter's syndrome. Many organs or
      systems can be affected. In addition to eradication of the initiating infection,
      treatment is mainly symptomatic and management is multidisciplinary.

PMID- 9611358
TI  - [Rare testicular tumors].
AB  - We report one case of "sex-cord stromal tumor" composed by Leydig and Sertoli
      cells. An epidermoid cyst of the testicle will be described. Finally, a case of
      scrotal leiomyoma is reported.

PMID- 9611359
TI  - Endoscopic percutaneous drainage of a renal echinococcal cyst during percutaneous
      nephrolithotomy.
AB  - In Morocco, hydatid disease is endemic and constitutes a major problem of public
      health. Renal echinococcal cyst ranks third after pulmonary and hepatic
      locations. We report a case of renal echinococcal cyst diagnosed during
      percutaneous nephrolithotomy which was treated endoscopically. To our knowledge,
      this situation has not been reported previously in the literature.

PMID- 9611360
TI  - [Application of the laryngeal mask for elective percutaneous dilatation
      tracheotomy].
AB  - Percutaneous dilatational tracheostomy is an increasingly accepted procedure for
      bed-side tracheostomy. The exact positioning of the endotracheal tube, the
      localization of the point for puncturing the trachea and damage to the
      endotracheal tube and the cuff as well as to the bronchoscope due to the
      puncturing process are technical problems which can endanger the course of the
      operation. In a prospective randomized study, we examined whether use of the
      laryngeal mask airway (LMA) is a real alternative to the endotracheal tube during
      tracheostomy. Of 48 consecutive patients only 43 fulfilled all criteria for this
      study: PaO2 > 100 mmHg, PaCO2 < 45 mmHg (in patients with head injury < 35 mmHg)
      under intermittent positive pressure ventilation (IPPV) with a mean ventilation
      pressure of < 25 mmHg and an FiO2 of 1.0. Patients with intestinal obstruction,
      hemorrhages of the mouth and nose and unfavourable anatomic conditions were not
      included in this study. Three more patients had to be excluded from the study
      because of technical problems. In 21 patients tracheostomy was performed using an
      endotracheal tube (ET group) and in 19 patients using a LMA (LM group). After
      positioning of the endotracheal tube or the LMA, tracheostomy was performed in
      the usual way. Arterial blood gases (PaO2 and PaCO2) were investigated before
      positioning of the endotracheal tube or the LMA, five minutes after this
      procedure and five minutes after the end of tracheostomy. Mean arterial pressure
      (MAP), heart frequency (HF) and peripheral oxygen saturation (SpO2),
      endexpiratory CO2 partial pressure (PetCO2) and minute ventilation volume (MVV)
      were registered every 60 seconds. The ET group and LM group did not differ
      regarding basic diseases, age and severity of illness. Before the beginning of
      tracheostomy, there were no differences in MAP, HF, SpO2, PetCO2 and PaCO2
      between the two groups. Before tracheostomy, only PaO2 was significantly higher
      in the LM group than in the ET group. Immediately before the insertion of the
      tracheal cannula and five minutes after the end of tracheostomy, there were no
      differences in the measured parameters of the two groups. An increase in PetCO2
      and a decrease in minute ventilation volume were observed in both groups.
      Regarding technical complications, the LMA is a safe alternative to the
      endotracheal tube. The choice of method should depend on the basic disease and
      the patient's ventilation requirements at the time of tracheostomy, while there
      is still a call for safe instruments guaranteeing sufficient sealing of the
      respiratory tract during the dilatational tracheostomy and simultaneous avoidance
      of technical problems during puncturing of the trachea and widening of the point
      of puncturing.

PMID- 9611361
TI  - [Is the laryngeal mask a viable alternative to endotracheal intubation in
      adenoidectomies in children?].
AB  - Based on our results and experiences, we consider the laryngeal mask anaesthesia
      a recommendable alternative to endotracheal intubation anaesthesia for
      adenotomies in children. Prerequisites with regard to the highest possible safety
      for the patient are specialist's knowledge, close anaesthesiological
      otolaryngological cooperation and continuous clinical and apparative monitoring
      in order to detect possible accidental dislocations of the laryngeal mask without
      any delay. Using the laryngeal mask, disadvantages of endotracheal intubation,
      such as lesions of the vocal cords and damages to the tracheal mucous membrane
      can be avoided and the total time of narcosis can be reduced on average by about
      five minutes, particularly by shortening the recovery time of anaesthesia.

PMID- 9611362
TI  - [Intubating laryngeal mask].
AB  - To improve the success of blind intubation through a laryngeal mask, Dr. A.I.J.
      Brain constructed the intubating laryngeal mask airway (ILMA), marketed under the
      name Fastrach. The new construction allows blind intubation with highly flexible
      endotracheal tubes up to 8 mm ID with cuff (straight Woodbridge type), securing
      the airway around the intubation process and maintaining most of the
      characteristics of a standard laryngeal mask airway (SLMA), including
      contraindications. An additional contraindication is the existence of a Zenker
      diverticle. Up to now, eight working groups reported a success rate of blind
      intubation through the ILMA of more than 90% in about 1,200 patients, with a
      success rate of blind intubation of more than 50% for the first intubation
      attempt. Ten percent of the patients were difficult to intubate with the same
      success rate for blind intubation as in normal patients. Reduced mouth opening
      does not seem to hinder the use of the ILMA in spite of its increased outer
      diameter of 2 cm, as long as it is possible to enlarge the mouth opening to > 2
      cm during anaesthesia. The new ILMA more than doubles the success of blind
      intubation compared to an SLMA, irrespective of a large variety of intubation
      difficulties. Correct judgement of endotracheal tube position is mandatory. The
      ILMA has the potential to be used in patients who are difficult to intubate and
      to substitute the SLMA in "cannot ventilate--cannot intubate" situations. The
      future will show if the ILMA also will improve emergency airway management by
      inexperienced personnel, including intubation, as has been shown for the standard
      laryngeal mask airway in cardiopulmonary resuscitation for ventilation only.

PMID- 9611363
TI  - [Sore throat after use of the laryngeal mask and intubation].
AB  - The laryngeal mask was developed by Brain in 1981 and described for the first
      time in 1983. It has been applied a few million times worldwide since 1988. One
      of the main complication is soreness of the throat. Two hundred unselected
      patients who had gynaecological procedures under general anaesthesia--100 under
      laryngeal mask airway and 100 under intubation--were surveyed to ascertain the
      incidence of sore throats under laryngeal mask airway. Each patient was asked
      about soreness of the throat during the next two days. The incidence and duration
      of sore throats were recorded using a pain scale (0-100). After narcoses with the
      laryngeal mask, 63 patients had no complaints. Thirty-seven had sore throats with
      an average pain score of 8.1 +/- 13.8 on the day of operation. The average pain
      scores showed a decreasing tendency (4.2 +/- 9.5 and 0.4 +/- 2.6) for the first
      and second postoperative day. After intubation narcoses, we recorded sore throats
      significantly more frequently (p < 0.05) and the average pain score on the day of
      operation was significantly higher (13.2 +/- 17.5; p < 0.05) than after narcoses
      with the laryngeal mask. Also after narcoses with the laryngeal mask, the average
      pain scores decreased quickly on the first and second postoperative days (5.1 +/-
      9.0 and 0.2 +/- 1.4). There were no differences regarding sore throats between
      narcoses with the laryngeal mask or intubation on these two postoperative days.
      Using both anaesthesiological methods, sore throat was not related to duration of
      anaesthesia or the experience of the anaesthetist.

PMID- 9611364
TI  - [Hepatotoxic encephalopathy versus Leigh syndrome--a case report].
AB  - Low perfusion of the liver due to hypovolaemia and sepsis-induced pathological
      distribution of blood volume can lead to severe liver disturbances. Damage to the
      liver as shock organ is manifold and affects other functions. Increased serum
      levels of ammonia and zerebral symptoms with disturbances of neurotransmission
      are responsible for the development of encephalopathia. Based on a case report,
      the differential diagnosis of Leigh-Syndrome as a mitochondric encephalopathy
      with uniform morphologic form is discussed. Long lasting parenteral nutrition,
      sepsis, metabolic imbalance and disturbance of the electrolyte balance can
      influence the extent of the mitochondric encephalopathy.

PMID- 9611365
TI  - Blood lactate disappearance during breathing hyperoxic gas after exercise in two
      different physical fitness groups--on the workload fixed at 130% AT.
AB  - This study aimed to investigate the effects of hyperoxic gas breathing on the
      disappearance of blood lactate after exercise in two groups having different
      physical fitness and to determine the most effective O2 concentration in
      consideration of workload. Our previous study has demonstrated that hyperoxic gas
      breathing brought out different effects among subjects. In respect of these
      effects, it was thought necessary to pay attention to exercise intensity.
      Therefore, the exercise intensity of this study was set by using relative
      workload of anaerobic threshold (AT) from the aspect of blood lactate. Ten
      healthy male students participated as subjects and were divided into 2 groups; a
      group consisting of 5 active students whose mean AT was 60.4% VO2max (Higher AT
      group) and the other group consisting of 5 inactive students having the mean AT
      of 48.8% VO2max (Lower AT group). All subjects underwent three cycles of
      ergometer exercise on a bicycle (workload; 130% AT) for 5 min and recovery
      session for 6 min. The hyperoxic gas breathing was given only for the recovery
      session. The conditions of breathing were air, 30, 40, 60 or 80% O2. Blood for
      determination of the blood lactate level was taken only in the recovery session.
      When compared with air-breathing, the blood lactate level was significantly
      reduced in the condition of more than about 60% O2 breathing in Higher AT group,
      but not in Lower AT one. Together with the previous findings, it was found that
      the blood lactate level was markedly reduced by more than 60% O2 breathing in
      Higher AT group without relation to the workload in the range of about 70 to 80%
      VO2max. In Lower AT group, however, the effects of hyperoxic gas breathing were
      dependent on the exercise intensity; 30% and 40% O2 breathings were effective for
      the subjects with more than about 65% VO2max, but not in a lower intensity than
      it. These results indicate that the effects of hyperoxic gas breathing on the
      disappearance of blood lactate are dependent on the exercise intensity and the
      physical capacity.

PMID- 9611366
TI  - Lateral difference in the reproduction of arm positioning movement: an
      examination of the hypothesis on the levels of psychological processes.
AB  - The purpose of this study was to determine whether the hypothesis on the levels
      of psychological processes (Hatta, 1977, 1978) accounts for lateral differences
      in arm positioning movement (a spatial localization task). Fifteen right-handed
      male subjects were asked to perform a constrained criterion movement, 12 cm in
      length, with the left or right arm. Then, after a 10-sec retention interval, they
      were asked to perform the movement with the same arm, estimating lengths of 6, 12
      or 24 cm. Different levels of psychological processes were assumed to be involved
      in estimating these various movement lengths--half, the same, or double that of
      the original. All possible combinations of the arm (left/right) and three
      movement length were tested. The CE scores were lower (more accurate) for the
      left arm (half; 1.5 +/- 8.1 mm, same; 4.3 +/- 6.2mm, double; 5.9 +/- 20.3 mm)
      than those for the right arm (half; 5.9 +/- 7.6 mm, same; 10.6 +/- 10.6 mm,
      double; 11.8 +/- 23.6 mm) in all conditions, indicating a lateral difference (the
      right hemisphere dominance) in arm positioning tasks. This typical lateral
      difference, which displayed no significant difference among conditions, is
      supposed to be mediated by complex or high-level psychological processes. These
      psychological processes are required by the subjects in the estimation of the
      various movement lengths. This study suggests that the level of psychological
      processes is a crucial factor in the manifestation of lateral differences in the
      performance of arm positioning movements.

PMID- 9611367
TI  - Comparison of diets among elderly female residents in two suburban districts in
      Chiang Mai Province, Thailand, in dry season--survey on high- and low-risk
      districts of lung cancer incidence.
AB  - By means of duplicate meals, we collected food samples of general female
      residents, aged 50 to 74 years at two suburban districts in Chiang Mai Province,
      which are distinguished by very high and low incidence rates of lung cancer.
      Then, on the basis of analyses of their consumption of foods by food groups, we
      compared their dietary habits in the dry season of northern Thailand with special
      reference to the difference in lung cancer incidence. In brief, the following
      features and difference in their dietary habits were found; 1) Rice, vegetables,
      and pork were most frequently eaten in both the districts. 2) Consumption of
      fruits, in both quantity and variety, at a high-risk district was much less than
      that at a low-risk district. 3) Female residents at a low-risk district consumed
      more variety of green and yellow vegetables than those at a high-risk district.
      4). Potato was not found in food samples of a high-risk district. 5)
      confectionery was more prevalent in a low-risk district than at a high-risk
      district.

PMID- 9611368
TI  - Cloth color preference under the influences of body heating due to hot bath
      immersion.
AB  - The experiment is aimed at knowing the effect of "body heating" on color
      preference. Eleven subjects with normal color vision served as subjects. Two
      tests, one of the "No Bath" and the other of the "Bath" were conducted. Hot bath
      immersion with 38.5 degrees C was performed for 30 min from 07:30 h to 08:00 h.
      Then, they were instructed to choose a single colored cloth out of 41 cloth
      colors (24 x 52 cm), preferred by themselves, every five min from 08:00 h to
      09:00 h under the ambient temperature (Ta) of 27 degrees C. Most subjects
      preferred cooler color after "body heating" than after "not body heating". This
      finding was discussed in terms of greater differences between core temperature
      and its set point after "body heating", because cooler color would be helpful
      psychologically in allowing raised core temperature approach its set point.

PMID- 9611369
TI  - A proposal of optimal floor surface temperature based on survey of literatures
      related to floor heating environment in Japan.
AB  - Due to comprehensive research on floor heating in Japan and abroad over the last
      twenty years it is possible today to predict these combinations of comfortable
      conditions. The specific aim of this investigation is to obtain experimental data
      upon which the comfortable range of the floor surface temperature could be based,
      thereby providing a practical and more satisfactory design guide. Accordingly
      literatures on floor heating are collected and investigated with the purpose of
      revealing what the comfort range of floor surface temperature ought to be.
      Authors tried to obtain a comfortable and permissible floor surface temperature
      and then reconfirm the maximum comfortable range so that they can propose a
      reasonable comfortable floor surface temperature and make it fit for practical
      and extensive use. After synthesizing all the comfortable and permissible values
      reported in many other papers, this paper finally advances a suggestion on the
      optimal and permissible floor surface temperatures. Results concerning this
      subject are as follows. The lowest floor surface temperature would be limited to
      25 degrees C, and it is 21-23 degrees C for the air temperature so that more than
      80% subjects can be expected to be comfortable within this recommended
      temperature interval.

PMID- 9611370
TI  - New apparatus stimulating the region of tongue innervated by glossopharyngeal
      nerve and its application to monosodium glutamate (MSG) solution.
AB  - Some apparatuses stimulating the region of tongue innervated by chorda tympani
      nerve were well known and they were used popularly, but the apparatuses for
      glossopharyngeal nerve were not produced yet. In the study, the apparatus for the
      stimulations of glossopharyngeal nerve was trially produced. It was known that
      the substance of "Umami" was responded well in the tongue region innervated by
      glossopharyngeal nerve. The evoked potential for the stimulations of monosodium
      glutamate (MSG) solution which was known as substance of Umami was measured with
      the use of the trial stimulating apparatus. The evoked potential was detected by
      monopolar lead for the positions between Cz and A1 (left lobe) with the ground at
      Fpz. The evoked potential of MSG consisted of a positive peak wave with the
      latency at approximately 250 ms. The amplitudes increased and the latency
      decreased as the concentration of MSG increased. The evoked potential stimulating
      the tongue innervated by this glossopharyngeal nerve could be detected for the
      first time by the use of the trial apparatus.

PMID- 9611371
TI  - Estimation of thermal sensation during varied air temperature conditions.
AB  - Seven male students were exposed to four varied air temperature environments: hot
      (37 degrees C) to neutral (27 degrees C) (HN), neutral to hot (NH), cool (17
      degrees C) to neutral (CN), and neutral to cool (NC). The air temperature was
      maintained at the first condition for 20 min, then was changed to the second
      condition after 15 min and was held there for 20 min. Each subject wore a T
      shirt, briefs, trunks, and socks. Each sat on a chair and was continuously
      evaluated for thermal sensation, thermal comfort, and air velocity sensation.
      Some physiological and thermal parameters were also measured every 5 s during the
      experiment. The correlation between thermal sensation and skin temperature at 15
      sites was found to be poor. The subjects felt much warmer during the rising phase
      of the air temperature (CN, NH) than during the descending phase (HN, NC) at a
      given mean skin temperature. However, thermal sensation at the same heat flux or
      at the same value of the difference between skin and air temperature (delta(Tsk -
      Ta)) was not so different among the four experimental conditions, and the
      correlation between thermal sensation and heat flux or delta(Tsk - Ta) was fairly
      good. The multiple regression equation of the thermal sensation (TS) on 15 sites
      of skin temperature (Tsk; degrees C) was calculated and the coefficient of
      determination (R*2) was found to be 0.656. Higher coefficients of determination
      were found in the equations of thermal sensation for the heat flux (H; kcal.m-2.h
      1) at the right and left thighs of the subjects and on delta(Tsk - Ta) (degrees
      C) at 4 sites. They were as follows: TS = 2.04 - 0.016 Hright - 0.036 Hleft; R*2
      = 0.717, TS = 1.649 + 0.013 delta(Tsk - Ta)UpperArm - 0.036 delta(Tsk - Ta)Chest 
      0.223 delta(Tsk - Ta)Thigh-0.083 delta(Tsk - Ta)LowerLeg; R*2 = 0.752,
      respectively.

PMID- 9611372
TI  - Treatment of cutaneous Bowen's disease with particular emphasis on the problem of
      lower leg lesions.
AB  - Bowen's disease has a particular predilection for the lower leg, especially in
      women. A review of the literature for treating Bowen's disease is presented and
      the problems associated with treating the lower leg emphasized. Evidence for the
      various treatment modalities used to treat Bowen's disease largely comes from
      studies that lack good methodology in terms of standardized techniques, patient
      controls and adequate follow-up. In particular the widely accepted recommendation
      for excision is not supported by evidence that this treatment is superior to
      other modalities. The choice of treatment for Bowen's disease should take into
      account the patient's general condition, the site and size of the lesion.

PMID- 9611373
TI  - Sunscreens and vitamin E provide some protection to the skin immune system from
      solar-simulated UV radiation.
AB  - Previous studies have indicated that sunscreens designed to protect from erythema
      do not adequately prevent immunosuppression. Mice were irradiated with
      suberythemal doses of solar-simulated ultraviolet radiation (ssUVR) to assess the
      immunoprotective ability of sunscreens. Whereas C3H/HeJ and BALB/c mice had
      similar sensitivities to ssUVR-induced inflammation, C3H/HeJ mice were more
      sensitive to ssUVR-induced immunosuppression. Octyl dimethyl-p-aminobenzoic acid
      did not protect from immunosuppression and, thus, had an immune protection factor
      (IPF) of 1. 2-Ethylhexyl-p-methoxycinnamate and microfine titanium dioxide
      provided limited protection, both having IPF values of 1.127. Immune protection
      by the sunscreens appeared to be dependent upon absorption of UVA as well as UVB,
      and was much less than predicted from the sun protection factor. Vitamin E, an
      inhibitor of lipid peroxidation, also protected the immune system, with an IPF of
      1.2, indicating that oxidation of lipids is involved in UVR-induced
      immunosuppression, and that it should be possible to develop sunscreens which
      protect the immune system.

PMID- 9611375
TI  - Cytokeratins in primary cutaneous amyloidosis.
AB  - The expression of keratins was investigated immunohistochemically on formalin
      fixed and snap-frozen primary cutaneous amyloidosis tissue with a panel of
      monospecific and polyspecific antikeratin antibodies, with recognized keratins
      K1, K5, K6, K7, K8, K10, K14, K16, K17, K18 and K19. Amyloid deposits in frozen
      sections of seven cases of macular amyloidosis and lichen amyloidosus always
      reacted with antibodies LP34 (labelling K5, K6 and K18), MNF 116 (labelling K5,
      K6, K8, K10, K17 and K18), and RCK 102 (labelling K5 and K8); frozen sections in
      one case each of the seven cases also reacted with antibodies LL001 (labelling
      K14), LP1K (labelling K7 and K17), and LP2K (labelling K19). In formalin-fixed
      sections of 13 cases of macular amyloidosis and lichen amyloidosus, amyloid
      deposits were labelled with LP34 in three sections, MNF 116 in four sections,
      LL020 (labelling keratins K5 and K6) in one section, and LP2K in two sections. In
      nodular primary cutaneous amyloidosis, amyloid deposits were not labelled with
      any antikeratin antibodies. These data confirm that amyloid in macular
      amyloidosis and lichen amyloidosus contains keratin epitopes, and suggests
      derivation of the fibrillar component from keratin intermediate filaments.
      Several different keratins appear to undergo conversion to amyloid. LP34, MNF 116
      and RCK 102 antibodies, which have in common the labelling of keratin K5, may be
      useful in the diagnosis of macular and papular amyloidosis with frozen tissue
      sections.

PMID- 9611374
TI  - A philosophy for the Skin and Cancer Foundation.
AB  - The Skin and Cancer Foundation is now 21 years old in Sydney and 10 years old in
      Melbourne, and a third is being planned for Brisbane. The achievements of these
      institutions are quite remarkable but the philosophy on which they were based may
      not now be applicable. An understanding of this original philosophy may assist
      future planning. People suffering from skin disease in Australia need help which
      can only be delivered by a combination of several institutions such as
      government, hospitals and the Australasian College of Dermatologists (College).

PMID- 9611376
TI  - Subungual squamous cell carcinoma presenting with minimal nail changes: a factor
      in delayed diagnosis?
AB  - Squamous cell carcinoma of the nail bed is a relatively uncommon tumour that may
      be diagnosed only after considerable delay. The first case presented is a 79-year
      old man with a history of discomfort and discoloration affecting the right
      thumbnail of 3 years duration. The second case is a 70-year-old man who presented
      with a recurrent, offensive discharge from beneath the left thumbnail of 40 years
      duration. Clinical examination of the affected digits revealed minor nail
      abnormalities. The presence of tumour was fully apparent only after removal of
      the nail plate and inspection and biopsy of the nail bed. The cases demonstrate
      that subungual squamous cell carcinoma may present with prolonged symptoms and a
      deceptively benign appearance. The importance of consideration of the possibility
      of malignancy, removal of the nail plate for inspection of the nail bed and
      appropriate biopsy is emphasized.

PMID- 9611377
TI  - Allergic contact dermatitis to ethoxyquin in a farmer handling chicken feeds.
AB  - Farm workers handling animal feeds are exposed to a variety of chemicals, some of
      which may cause allergic contact dermatitis. A case of allergy to ethoxyquin (a
      preservative added to chicken feed to inhibit vitamin degradation) in a chicken
      farmer is presented. Although the offending allergen was identified in this
      patient, it proved difficult to find ethoxyquin-free chicken feed products and
      the patient's dermatitis persisted. When facing the clinical problem of
      dermatitis in animal workers, the possibility of allergic contact dermatitis to
      components in animal feeds must be considered.

PMID- 9611378
TI  - Concurrent infection due to Shewanella putrefaciens and Mycobacterium marinum
      acquired at the beach.
AB  - Infection with marine bacteria is uncommon. A patient with systemic lupus
      erythematosus who developed concurrent infection with Shewanella putrefaciens and
      Mycobacterium marinum (M. marinum) is described. After bathing leg ulcers in sea
      water, severe cellulitis of the left leg with necrotic areas and extensive bullae
      developed. Infection due to S. putrefaciens was confirmed and a long course of
      hospitalization, oral ciprofloxacin and skin grafting was required. During
      hospitalization subcutaneous nodules developed on the other leg. Biopsy revealed
      acid-fast bacilli and culture grew M. marinum. These lesions responded to
      rifampicin and cotrimoxazole. Patients with leg ulcers, peripheral vascular
      disease, diabetes, or receiving immunosuppressive drugs may acquire unusual
      infections after salt water exposure.

PMID- 9611379
TI  - Antineutrophil cytoplasmic antibody (ANCA)-positive cutaneous leucocytoclastic
      vasculitis associated with antithyroid therapy in Graves' disease.
AB  - Presented is a case of a 27-year-old male with Graves' disease on long-term
      propylthiouracil treatment who, when changed to carbimazole, rapidly developed a
      petechial and purpuric eruption on the legs, which subsequently flared on
      treatment with radioiodine. The clinical diagnosis of leucocytoclastic vasculitis
      was confirmed on skin biopsy. High-titre antineutrophil cytoplasmic antibodies in
      a perinuclear pattern (P-ANCA) were identified. No anti-myeloperoxidase activity
      was noted; therefore, the P-ANCA were classified in the atypical group. The
      target antigens, as determined by enzyme-linked immunosorbent assay, were
      lysozyme, lactoferrin and bactericidal/permeability increasing protein.
      Propylthiouracil and carbimazole are chemically related antithyroid drugs. There
      are reports of typical and atypical P-ANCA-positive cutaneous vasculitis due to
      propylthiouracil. Cutaneous vasculitis associated with atypical P-ANCA has not
      been noted previously to be temporally related to carbimazole use. The
      consideration of thionamides as possible aetiological agents in cases of P-ANCA
      positive drug-induced vasculitis is suggested.

PMID- 9611380
TI  - Partial face-sparing lipodystrophy (Kobberling-Dunnigan syndrome): report of a
      sporadic case.
AB  - A sporadic case is presented of a 20-year-old female with partial face-sparing
      lipodystrophy, also known as the Kobberling-Dunnigan syndrome with the Type 1
      clinical phenotype. This disorder affects the limbs and spares the face. The
      trunk is spared in the Type 1 phenotype but is affected in the Type 2 phenotype.
      The patient had the associated features of this syndrome including the
      hyperinsulinaemia, acanthosis nigricans and mildly raised triglycerides, but not
      diabetes mellitus.

PMID- 9611381
TI  - Adult cutaneous Langerhans cell histiocytosis.
AB  - A 24-year-old male presented with a 4 year history of a crusted erythematous
      papular eruption of the scalp and external auditory meati and a 12 month history
      of painful perianal ulceration. A diagnosis of Langerhans cell histiocytosis was
      made and confirmed by skin histology. Extensive investigation revealed no
      systemic involvement. Rapid improvement occurred after intravenous 2
      chlorodeoxyadenosine but relapse of perianal lesions occurred within 5 months.
      Local radiotherapy to the perianal region resulted in a complete remission
      sustained over 12 months.

PMID- 9611382
TI  - Idiopathic multiple miliary osteomas of the face.
AB  - A case of multiple miliary osteomas of the face arising in a 45-year-old
      Caucasian female with no history of skin disease is reported. Spontaneous
      development of numerous asymptomatic, skin-coloured facial papules had occurred
      over a 3 year period. Originally described in association with long-standing acne
      vulgaris, multiple miliary osteomas of the face has recently been reported in
      patients without prior skin disease. The pathogenesis, classification and
      treatment of this rare condition are discussed.

PMID- 9611383
TI  - Variable presentation of parvovirus B19 in a family.
AB  - This case report of the sequential presentation of parvovirus B19 in a family
      describes a 38-year-old woman initially presenting with 'gloves and socks'
      syndrome, along with her husband and five children who were also affected. A high
      clinical attack rate with prolonged illness and variable clinical presentations
      was demonstrated, including polyarthritis, erythema infectiosum and symptoms of a
      respiratory tract infection. In addition, the range of syndromes and clinical
      features of parvovirus B19 are presented.

PMID- 9611384
TI  - A continuum of neutrophilic disease occurring in a patient with ulcerative
      colitis.
AB  - A case of Sweet's syndrome (acute febrile neutrophilic dermatosis) occurring
      concurrently with bullous pyoderma gangrenosum is reported to emphasize the close
      relationship between these two disorders. Atypical pyoderma gangrenosum and
      Sweet's syndrome have been described as occurring simultaneously in
      haematological dyscrasias but not, to our knowledge, in ulcerative colitis. It
      has been proposed that pyoderma gangrenosum, Sweet's syndrome, erythema elevatum
      diutinum and subcorneal pustular dermatosis may represent manifestations along a
      continuum of neutrophilic dermatoses.

PMID- 9611385
TI  - Localized lichen sclerosus with nail loss.
AB  - A 52-year-old woman who developed a pale sclerotic second left toe with loss of
      the nail plate is described. Biopsy showed changes of lichen sclerosus. There
      were no other skin or genital lesions present.

PMID- 9611386
TI  - Allergic contact dermatitis to cocamidopropylbetaine in hair shampoo.
AB  - Allergic contact dermatitis to shampoo is rare. Report of a patient with
      widespread dermatitis caused by contact allergy to Kathon CG and
      cocamidopropylbetaine in shampoo used is presented.

PMID- 9611387
TI  - Intralesional bleomycin.
AB  - The use of intralesional bleomycin to treat Bowen's disease of the palm affecting
      a motor mechanic is presented. Bleomycin in 1% lignocaine was injected at 3-6
      week intervals to a cumulative total of 6.35 U. Follow-up at 18 months showed no
      local recurrence and no long-term adverse events.

PMID- 9611388
TI  - An outline of the history of dermatology in Victoria.

PMID- 9611389
TI  - What is the cost of onychomycosis?

PMID- 9611390
TI  - Response to the article, 'Local recurrence of melanoma'.

PMID- 9611391
TI  - [Biomechanics--mediator between technique and medicine].

PMID- 9611392
TI  - Techniques and equipment for muscle mechanics.
AB  - The individual in vivo mechanical properties of muscle groups are not well known,
      and these data are important in simulations of a subject's movements, and
      analysis of measured movements. Discrepancies in the force-velocity relation
      between in vivo and in vitro measurements have been documented in previous
      investigations. A powerful, high precision dynamometer was designed and built to
      make in vivo tests on the elbow and ankle joints. Test data obtained with this
      machine did not exhibit the same discrepancies observed in previous experiments,
      which leads to the conclusion that the previous discrepancies resulted from the
      test method used.

PMID- 9611393
TI  - Noninvasive assessment of stiffness and failure load of human vertebrae from CT
      data.
AB  - A calculational method based on noninvasively derived data for the assessment of
      the mechanical quality of individual vertebrae is presented. Dimensional data
      obtained from serial, segmented CT scans were used as the geometric input for a
      newly developed finite element model designed to calculate stiffness and failure
      load of these complex bone structures. Mechanical, structural data for cancellous
      bone was obtained by measurements of the compressive strength and failure load of
      actual vertebral specimens obtained at autopsy. The stiffness and failure load
      calculated by the newly developed finite element model were compared with the
      data obtained from mechanical measurements of vertebral specimens. A high
      correlation between measured and calculated failure load was found (r = 0.89, p <
      0.001, n = 16). The correlation between the failure load and bone mineral density
      (BMD) was significant (r = 0.82, p < 0.001, n = 16). A similar correlation
      between calculated and measured stiffness (r = 0.81, p < 0.001, n = 15) was also
      found using the finite element model described herein. Thus the newly developed
      calculation methodology has been verified and can be used to predict the failure
      load and stiffness of osteoporotic vertebrae using data obtained non-invasively
      from CT scans.

PMID- 9611394
TI  - Mechanical strength of fracture plates made of titanium for functionally stable
      mandibular reconstruction.
AB  - Plates for functionally stable mandibular reconstruction are successfully
      introduced with biocompatible titanium. While screws have been the subject of
      numerous investigations, only few results are available for the mechanical
      stability of plates. This contribution gives an overview about experimental
      possibilities to test plates in tensional, bending, and torsional strength as
      well as fatigue, and reports results about plates made of titanium and oxygen
      alloyed titanium. The alloyed material is harder, stiffer and shows higher
      tensile strengths. In contrast to softer titanium, contouring procedures during
      implantation can lead to structural defects and an associated higher fracture
      risk.

PMID- 9611395
TI  - Biofluid mechanics.
AB  - The flow behavior of biological fluids in living organisms plays a crucial role
      in determining the state of the tissue through which they flow. Biofluid
      mechanics, the study of the fundamentals of biological fluid flow, has been
      recognized to be extremely important for the understanding of how changes in the
      flow behavior within living tissue maybe affect both the fluid and the tissue.
      Fluids in living tissue include blood, water, air and bodily fluids of animals,
      as well as the fluids in plants. The movement and balance of forces in resting
      fluids and fluids in motion are among the basic subjects for research. Biofluid
      mechanics is a field whose importance to the field of bioengineering has
      increased over the last two decades as pharmaceuticals, biomaterials and non
      invasive diagnostic and surgical procedures create changes in the fluid mechanics
      of biofluids. Biofluid mechanics is a complex field including one of the most
      important areas of study--blood flow and cardiovascular diseases.

PMID- 9611396
TI  - Biomechanical differential equations of variables of the arterial pulse based on
      vessel wall and blood flow features.
AB  - A dynamic arterial vessel model with an associated flow resistance is deduced in
      Laplace-transformed form based on a linear dynamic muscle model and a laminar
      instationary blood stream with accompanying parameters (such as elasticity, actin
      myosin overlap, movement resistances, blood stream resistance and blood mass). In
      addition, a flow resistance is connected at the outlet of the vessel. With the
      pulse pressure course as the given input, the Laplace-transformed definition
      enables, in a clearly arranged manner, the derivation of differential equations
      of several variables of the arterial pulse process--the changes of blood inflow,
      outflow, storage flow or volume, of the internal vessel pressure, of the output
      pressure, of the various pressure differences over the vessel, of the vessel wall
      tension, of the vessel radius and the vessel wall thickness. The derivations
      yield the order and the structures of these differential equations. The
      coefficients of these equations are complicated functions (sums and products) of
      the smooth-muscle, blood-flow and geometrical parameters. Only in special cases-
      with an open or the closed vessel at the outlet--are the coefficients simple
      functions of the vessels parameters.

PMID- 9611397
TI  - Analysis of respiratory mechanics during artificial ventilation.
AB  - Mechanical or artificial ventilation is the most important life-saving
      therapeutic instrument in modern intensive care medicine. The ventilator takes on
      the convective transport of the respiratory gas, i.e. delivery of oxygen and
      removal of carbon dioxide. The technical gas delivery system (ventilator,
      respiratory tubing system, gas humidifier) and the respiratory system (lungs and
      thorax) of the patients form a connected pneumatic system of high complexity. The
      respiratory system produces a mechanical impedance to ventilator output.
      Impedance is composed of an elastic, a non-elastic, i.e. resistive, and an
      inertive part. The corresponding indices describing respiratory mechanics are
      compliance, flow resistance and inertance. Based on the equation of motion of the
      respiratory system, several methods of analysing respiratory mechanics during
      mechanical ventilation are described. Quantitative analysis of respiratory system
      mechanics (a) is a prerequisite for the understanding of the complex patient
      ventilator interaction, (b) provides important clinical information on pulmonary
      function and the course of disease, and (c) allows the physician at the bedside
      to adjust the ventilatory settings to the needs of the individual patient.

PMID- 9611398
TI  - [Human immunodeficiency virus and acute renal insufficiency].
AB  - We describe here the broad spectrum of acute renal insufficiency occurring in the
      course of human immunoinsufficiency virus infection. In our renal unit in Tenon
      hospital, 90 human immunoinsufficiency virus-infected adult patients were
      admitted for acute renal insufficiency between June 1988 and December 1996. Sixty
      out of them had a pathological diagnosis. The remaining patients did not have
      renal biopsy because of obstructive renal failure (n = 2), bleeding risk (n =
      11), or clinically evident hypovolemic and/or sepsis-related acute tubular
      necrosis (n = 17). Nine different causes of acute renal insufficiency were
      listed. Human immunoinsufficiency virus-associated nephropathy, the most specific
      human immunoinsufficiency virus-related renal disease, which was diagnosed in 14
      patients, is characterized by focal and segmental glomerulosclerosis with an
      important hyperplasia and/or proliferation of podocytes and huge tubular
      distension. The rapid progression to end-stage renal failure was not a constant
      feature since 10/14 patients had a partial renal recovery. Hemolytic-uremic
      syndrome was the other major cause of acute renal failure in these patients (32
      cases) and was found to be associated with active cytomegalovirus infection.
      Cytomegalovirus-infected cells were present in half of the renal biopsies
      performed in this group of patients. Furthermore, these patients had an increased
      plasma tissue-type plasminogen activator activity whereas its type 1 inhibitor
      was not significantly increased, as opposed to non human immunoinsufficiency
      virus-associated hemolytic-uremic syndrome. Half of the patients had a complete
      renal recovery. The other causes of acute renal insufficiency were 1)
      intratubular deposition of either drugs (Adiazine, Foscavir, Indinavir) in 13
      patients, or monoclonal light chain in one patient with B cell-lymphoma; 2) lupus
      like glomerulonephritis characterized in one case by a complete clinical
      remission after 6 month-treatment by antiproteases; 3) acute tubular necrosis. In
      this setting, rhabdomyolysis could reveal HIV infection. The heterogeneity of
      renal diseases could be explained by the variation of human immunoinsufficiency
      virus-associated infections along time and by the different drugs which permit a
      better survival. We can hypothesize that new HIV-associated diseases will occur
      with the long term use of antiproteases.

PMID- 9611399
TI  - [Role of the hemobiologist in the detection and prevention of post-transfusional
      hepatitis].
AB  - To prevent post-transfusional hepatitis B and C, two epidemiologic studies were
      performed. The first, based on the frequencies distribution of hepatitis B virus
      serological markers versus sex and classes of age, has permitted the assessment
      of the profile of the infection in a population composed of 573 north vietnamese
      blood donors. There is no significant difference between men and women
      frequencies of HBs antigen (11.5%), anti-HBs antibody (70.2%) and anti-HBc
      antibody alone (3.8%), but a significant difference of no-marker frequencies:
      7.8% and 17.9% in men and women respectively (X2 = 9.11; p = 0.010). The
      percentage of no-marker decreases when the mean age of each class increases. The
      second, using the increase of the serum alanine aminotransferase (ALAT) activity
      as an indirect marker of non-A, non-B hepatitis for determining in a population
      of more than 25,000 parisian blood donors, the percentage of donors eliminated.
      They are between 0.70 and 0.76 in women and 2.26 and 2.46 in men. These
      investigations can be applied to prevent the hepatitis B transmission in a
      population of 102 south vietnamese women in age to procreate or to determine the
      percentage of blood donors eliminated (3.12%) in a population of 2,950 Parisians
      composed in majority (50.9%) of new donors. The hemobiologist will have an
      important role to elaborate strategies for orientation of blood gifts with
      hepatitis B and C virus markers.

PMID- 9611400
TI  - [Iodine deficiency in the Cirque of Salazie (Reunion Island). Analysis of
      nutritional causes and study of their consequences].
AB  - Randomized subjects (n = 294), (35 young children, 6-30 months old--91 children
      8.6 +/- 0.7 years, 116 teenagers 13.2 +/- 1.9 y--52 young women 28.5 +/- 6.1 y)
      leaving in a mountainous area of Reunion Island (Cirque de Salazie) were
      evaluated according to the following: a questionnaire related to food intake,
      cervical palpation for thyroid size evaluation and collections of urine and foods
      (natural and mineral water, breast and commercial milk and salt) for iodine
      measurement. Neonatal TSH of 308 new borns in Salazie were compared to TSH of 300
      new-borns of Lille (France). The prevalence of goiter increases with age (0% in
      young children, 12.1% in children, 23.3% in teenagers, 38.4% in women) whereas
      median urinary iodine (microgram/dl) decreases in the same groups (12-7.8-5.6
      4.2). The intake of milk and dairy products significantly decreases from children
      to adults. Neonatal TSH values are significantly higher in Salazie than in Lille
      (p < 0.005). Natural and mineral water, breast milk and salt contain little
      iodine. In conclusion iodine deficiency is present in this area of Reunion Island
      with a significant increment of neonatal TSH values.

PMID- 9611401
TI  - [Genetic factors, Na K ATPase activity and neuropathy in diabetics].
AB  - A genetic predisposition to develop a polyneuropathy in case of diabetes seems to
      exist. Some ethnic groups such as North Africans are prone to develop a diabetic
      polyneuropathy. To identify this predisposition could help in targeting a
      preventive treatment. We have observed that red cell Na/K ATPase activity was
      lower among diabetic patients than controls and even lower when diabetic
      neuropathy was present. Now an impaired NA/K ATPase activity has been implicated
      in the pathogenesis of diabetic neuropathy and ethnic differences in this enzyme
      activity have been demonstrated. For these reasons, we have compared red cell
      Na/K ATPase activity of European and North African individuals with or without
      diabetes and in case of diabetes with or without neuropathy. Among European
      subjects, Na/K ATPase activity was higher in 46 control subjects than in 84
      insulin-dependent diabetic patients (405 +/- 16 nmol.mg Prot-1h-1 versus 282 +/-
      10 p. < 0.05) and in the diabetic group Na/K ATPase activity was lower in the
      patients presenting with neuropathy (242 +/- 19 versus 323 +/- 12 p. < 0.05). The
      mean red cell Na/K ATPase activity was lower in 16 North African control subjects
      than in their European counterparts (296 +/- 26 p. < 0.05). The same observation
      was made when comparing 24 North Africans insulin dependent diabetic patients to
      the European diabetics (246 +/- 20 p. < 0.05). A low Na/K ATPase activity appears
      to be a risk marker of diabetic neuropathy. It could explain the propensity of
      North African patients to develop this diabetic complication. A restriction
      polymorphism exist on the first intron of the ATP1 A1 gene coding for the ATPase
      alpha 1 isoform. This isoform is preponderent in the nervous tissue and exclusive
      in red cells. Among European diabetic individuals, the presence of the restricted
      allele is strongly associated to diabetic neuropathy, confering a relative risk
      of 6.5 (95%, confidence interval 3.3-13). The restricted allele is associated to
      a lower Na/K ATPase activity but only among diabetic patients and not in control
      subjects. This fact suggests an interaction between genetic factors (the
      restriction polymorphism of ATP1 A1 gene) and environmental factors (diabetes) to
      induce a decrease in Na/K ATPase activity which in turn could favor the
      development of diabetic neuropathy. Among North African individuals the
      impairement of Na/K ATPase activity is not explained by the presence of this
      polymorphism. Other genetic factors remain to be identified.

PMID- 9611402
TI  - [Prevention of injurious effects of ultraviolet rays].

PMID- 9611410
TI  - The distribution of foodborne disease by risk setting--Ontario.

PMID- 9611411
TI  - Potential hazards of bat rehabilitation--Manitoba.

PMID- 9611412
TI  - Respiratory virus surveillance. FluWatch Project.

PMID- 9611413
TI  - Disseminated bacille Calmette-Guerin infection: three recent Canadian cases.
      IMPACT. Immunization Monitoring Program, Active.

PMID- 9611414
TI  - A rare manifestation of parathyroid carcinoma presenting as a cystic neck mass.
AB  - Parathyroid carcinoma is a rare endocrine neoplasm. An unusual case is reported
      where a patient presented with a cystic neck mass and hypercalcemia. A review of
      the Connecticut Tumor Registry data revealed that four cases were encountered
      statewide over years 1988 to 1993. A brief overview of the current literature
      follows.

PMID- 9611415
TI  - Significance of coagulase-negative staphylococci in urinary tract infections in a
      developing country.
AB  - The biotyping of 154 (3.8%) coagulase-negative staphylococci from 4,051 urinary
      specimens in males and females was performed. Their significance and
      antimicrobial susceptibility patterns were also evaluated. S. saprophyticus and
      S. epidermidis accounted for approximately 90% of isolates from females, while in
      males only 68.7% of isolates were S. epidermidis, S. hominis, S. xylosus, S.
      simulans, and S. hyicus, The mean age for females with infections due to S.
      saprophyticus was 23 years while for males with infections due to S. epidermidis
      it was 77 years. The mean age for infections due to other staphylococci was
      higher in males than in females. There was little variation in the antimicrobial
      susceptibility pattern in the various species. The results suggest that apart
      from S. saprophyticus and S. epidermidis, six other species of coagulase-negative
      staphylococci (S. hominis, S. xylosus, S. simulans, S. hyicus, S. hemolyticus,
      and S. cohnii) account for most urinary tract infections irrespective of gender.

PMID- 9611416
TI  - Systemic cat scratch disease: a brief case report and review of the literature.

PMID- 9611417
TI  - Intrinsic hemangiomas of the peripheral nerves report of a case and review of the
      literature.
AB  - A case of intrinsic hemangioma of the peripheral nerves and the diagnostic and
      therapeutic problems associated with these tumors is reviewed. Of the
      preoperative studies available, magnetic resonance imaging and to a lesser degree
      computed axial tomography are the most helpful in diagnosis. Angiograms are not
      helpful. Specific laboratory studies to evaluate lymphoproliferative disorders
      are necessary if lymphadenopathy can be ruled out. Needle biopsies should be
      avoided as they may result in nerve injuries. During surgery the recognition of
      the tumor as a hemangioma is of prime importance in order to avoid damage to the
      nerve structures. More aggressive resections that might sacrifice the nerve
      should be postponed if an intraoperative diagnosis is not possible. This will
      provide for a complete histopathological evaluation rather than reliance upon
      frozen section interpretations.

PMID- 9611418
TI  - Monitoring clinical quality in Medicaid managed care.
AB  - With the recent exponential growth in managed-care plan enrollment by Medicaid
      beneficiaries, a variety of quality monitoring systems have emerged. This paper
      argues that existing quality monitoring systems, originally designed for use by
      employers in the private sector, are a useful starting point for quality
      monitoring in the Medicaid program, but that substantial enhancements are needed
      to provide adequate quality assurance for Medicaid beneficiaries. This paper
      describes the development of a range of indicators for monitoring the clinical
      aspect of the quality of care for Medicaid beneficiaries and offers a framework
      for adapting existing monitoring systems to the needs of the Medicaid population.
      This work is part of a larger collaborative effort by the Connecticut Department
      of Public Health and the Department of Epidemiology and Public Health of Yale
      University School of Medicine to develop a blueprint for state government's role
      in quality assessment and performance management for managed care.

PMID- 9611419
TI  - Ongoing physician guidance to achieve periodic mammography of women at an urban
      health center.
AB  - The use of a low-cost behavior prompt at an urban, hospital-based health center
      that encourages physicians to record and act upon cancer screening information is
      described. Brief audit forms were incorporated into medical records of all women
      40+ years of age seen between June 1994 and March 1996 (approximately 4,700
      office visits). Audit forms alerted physicians about women's breast and cervical
      cancer screening histories and encouraged them to note any screening done or
      recommended during an office visit. Patient attributes did not readily
      distinguish who was and was not screened with mammography at recommended
      intervals, nor whether physicians did or did not address those needs for
      examination. On the other hand, explicit, continuous monitoring in medical
      records of the cancer screening status of women was associated with outcome
      variables. Availability of information on prior cancer screening activities
      significantly increased the odds that women were "on-time" for examinations as
      well as that physicians addressed the needs of women who were "past due" for
      mammograms at the time of their office visits.

PMID- 9611420
TI  - The need for single-payer catastrophic health insurance.
AB  - Both physicians and patients are becoming increasingly frustrated with the
      decreasing flexibility of our health-care system. Forty-one million citizens
      remain uninsured while ill patients in managed-care plans find themselves subject
      to bureaucratic hurdles in attempting to obtain necessary care. Rather than
      relying on the market place to provide affordable insurance to patients,
      physicians should embrace single-payer catastrophic coverage. A government
      insurance program should be enacted that covers all medical bills that exceed a
      $15,000 deductible annually for families and a $10,000 deductible annually for
      individuals. Patients could then purchase plans through the private sector to
      cover these deductibles. While such a plan would require a tax increase, premiums
      would decrease, health insurance would become more affordable to low wage
      earners, and more treatment decisions would be made by physicians and patients.

PMID- 9611421
TI  - Cancer gene testing?

PMID- 9611422
TI  - So what about character?

PMID- 9611423
TI  - Student dental hygienists' work values: a measure of an emerging profession?
AB  - The purpose of this study was to compare the work values of students in the
      School of Dental Hygiene and the Faculty of Dentistry at the University of
      Manitoba, Canada, both with each other, and with national sample of Canadian
      practitioners in both fields. The study was an outgrowth of a larger study
      measuring the work values of graduating students in six faculties selected to
      represent the occupational classification system of John Holland. The English
      version of the Canadian form of the Values Scale which measures 20 work and life
      values, was used in this study. Differences in values found between the student
      hygienists and practitioners in both dentistry and dental hygiene may indicate a
      growing desire for professional status by dental hygienists. Value differences
      found between practising dentists and hygienists may reflect a traditional
      hierarchical relationship between these occupations. Limitations of the study and
      future research questions are discussed.

PMID- 9611424
TI  - Community hospices: their role in palliative care.
AB  - This feature article is the first of a series of three articles on
      hospice/palliative care which will be published in future issues of Probe. The
      remaining two features discuss hospice care case scenarios and the role of the
      dental hygienist in palliative care.

PMID- 9611426
TI  - The independent practice of dental hygiene: political economy, professionalism
      and policy.

PMID- 9611425
TI  - Reconnecting the mouth to the body.

PMID- 9611427
TI  - Mediation in the workplace.

PMID- 9611428
TI  - Towards the professional status of dental hygiene in Alberta.
AB  - Presently, despite formal advances toward professional status and the acquisition
      of some professional attributes, dental hygiene may or may not be recognized as a
      profession. While dental hygienists in Alberta have a professional association
      that regulates the practice of dental hygiene, other professional attributes have
      yet to be attained. As the province's dental hygiene leaders begin to prepare
      recommendations to the Alberta government for the practice and direction of
      dental hygiene in Alberta, it is valuable for them to understand the different
      perceptions held by those affected. The study reported in this paper investigated
      the perceptions of Alberta dental hygienists and dentists regarding the
      professional status of dental hygiene in the province. Dental hygienists were
      selected to participate according to employment setting, while dentists were
      randomly selected. The questionnaire consisted of both open and closed ended
      questions, including Likert Scale items. Data were collected from questionnaires
      returned by 111 dental hygienists and 109 dentists. Two main points emerged from
      this study. The first is that although all dental hygienists recognize dental
      hygiene as an emerging profession, perceptions held by dental hygienists employed
      in private practice settings vary from those held by dental hygienists employed
      in traditional community care or alternative practice settings. The second
      recurrent theme is that dentists, while recognizing the expertise of dental
      hygienists, wish to retain economic control of dental hygiene. The article
      concludes by offering recommendations designed to increase the development of
      dental hygiene as a profession.

PMID- 9611430
TI  - Strategies for population health--investing in the health of Canadians.

PMID- 9611429
TI  - Risk assessment for periodontal disease.

PMID- 9611431
TI  - Ethics case study: double exposure.

PMID- 9611432
TI  - Dental caries and mutans streptococci levels in preschool children: a community
      research pilot project.

PMID- 9611433
TI  - Periodontitis in the diabetic; host response and potential treatment.

PMID- 9611434
TI  - Ethics case study.

PMID- 9611435
TI  - A culturally-specific oral health program for high risk Vietnamese children.

PMID- 9611436
TI  - Psychological predictors of pain during dental hygiene treatment.
AB  - This study examined the role of catastrophizing (i.e. a tendency to exaggerate
      the threat value of potentially painful situations) in predicting pain experience
      during dental hygiene treatment. Participants in the research were 100 patients
      undergoing scaling and/or root planing procedures at Dalhousie University's
      Dental Clinic. Following treatment, participants completed the Pain
      Catastrophizing Scale, a measure of emotional distress, a pain scale, and the
      Dental Anxiety Scale-Revised. Participants who scored above the median on the
      Pain Catastrophizing Scale were classified as catastrophizers, participants who
      scored below the median were classified as noncatastrophizers. Results showed
      that catastrophizers reported significantly more dental anxiety, emotional
      distress and pain than noncatastrophizers; and that distress reactions were more
      pronounced in men that in women. Discussion focuses on the importance of
      addressing psychological factors in dental hygiene practice, particularly as they
      relate to reactions to dental hygiene procedures, and avoidance of dental care.

PMID- 9611437
TI  - The palliative care team and the dental hygienist.

PMID- 9611438
TI  - Enhancing accurate assessment of periodontal disease by improving radiographic
      interpretation.
AB  - One of the most difficult areas of radiographic interpretation is periodontal
      assessment--an area critical to the success of the role of today's dental
      hygienists charged with the responsibility of evaluation and treatment of
      periodontal disease. The accurate evaluation and interpretation of radiographs,
      used by dental hygienists in conjunction with a clinical periodontal examination,
      is essential for effective planning and provision of nonsurgical periodontal
      therapy and appropriate referral as necessary. Definitive assessments require
      high quality radiographs with the minimum of distortion. Currently, bitewing
      radiographs are the technique of choice for evaluation of periodontal structures,
      with the use of vertical bitewings (which allow the clinician to view osseous
      tissue in both arches simultaneously) recommended as disease progresses.
      Clinicians have complete control over the various technical factors which may
      affect the processed radiograph and consequently the periodontal interpretation.
      The procedures highlighted in this article will result in good diagnostic quality
      with the minimum of exposure to the patient. Accurate radiographic assessment
      also depends upon the ability of the hygienist to recognize the appearance of
      normal periodontal tissues as well as the periodontium in a diseased state.
      Because in the early stages of disease radiographic changes are difficult to
      observe, a keen, well-trained eye is required to see the slight alterations
      occurring in the periodontium. This article reviews the radiographic appearance
      of normal tissues and the generally accepted sequence of radiographic changes
      associated with periodontitis according to the American Academy of Periodontology
      (AAP).

PMID- 9611439
TI  - Oral management of the cancer patient. Part I: Overview of cancer and oral
      cancer.
AB  - As the population of older Canadians (50 + years) grows, so the number of people
      diagnosed with some form of cancer increases. Through early detection, diagnosis,
      and advances in treatment of these cancers, the number of long-term survivors is
      also increasing. It is, therefore, predictable that the role of all health care
      providers will increase in the areas of diagnosis, treatment, and assistance with
      their continued care. In this first of a three part series, an overview of cancer
      (and in particular oral cancer) is presented as well as statistical information
      on cancer incidence and mortality, etiology, treatment modalities, head and neck
      cancers, their signs and symptoms, prognosis, and pre-treatment dental
      evaluations. The second installment will review the care and management of
      patients undergoing chemotherapy and the third will discuss the care and
      management of patients receiving radiation therapy for head and neck cancers. The
      series will focus specifically towards the oral implications impacting on dental
      hygiene services.

PMID- 9611440
TI  - Understanding the determinants of preventive oral health behaviours.
AB  - Achieving oral health for the client is the goal of dental hygiene practice. The
      two major threats to oral health, dental caries and periodontal disease, can
      almost always be controlled if clients adopt appropriate oral health behaviours.
      A review of the literature indicates that many factors determine whether or not a
      client will adopt appropriate oral health behaviours. These factors include
      demographics, socialization, emotional status, perceptions and dental beliefs.
      Determining a client's attitudes towards oral health requires the active
      participation of both the client and the dental hygienist. Interview techniques
      borrowed from participatory and ethnographic research can be used during the
      assessment phase of the dental hygiene process to allow the dental hygienist to
      systematically explore the factors that may affect the practice of preventive
      oral health behaviours. Data gathered during this phase can then be used in the
      planning phase of the dental hygiene process to develop a strategy which is
      specifically designed to meet the assessed needs of the individual client.

PMID- 9611441
TI  - Self-policing: it's our duty.
AB  - As professionals, dental hygienists have a duty to protect the public from
      incompetent and unethical behaviour. This literature review was completed to
      provide a guide for dental hygienists who may not feel confident addressing
      errant behaviour. It discusses principles of biomedical ethics and uses Morriem's
      system of evaluating levels of adverse outcome as an assessment tool. Pertinent
      examples in dental hygiene practice are included. Investigation and resolution of
      dilemmas are also discussed with the aim of upholding the integrity of dental
      hygiene practice.

PMID- 9611442
TI  - Dental hygiene proprietorship.

PMID- 9611443
TI  - Sharpen your professional edge.

PMID- 9611444
TI  - Desquamative gingivitis.

PMID- 9611445
TI  - A focus group study: overview of the methodology.
AB  - The intent of this paper is to present an overview of focus group research
      methodology. The purpose of the exploratory and qualitative focus study was to
      investigate the status of dental hygiene as a profession. Information was
      gathered from four self-facilitating focus groups: first year dental hygiene
      students comprised the first group and the other three focus groups were
      comprised of practising dental hygienists. Criteria for defining a profession was
      established by the first focus group; further discussion from the other three
      focus groups was categorized, and if needed, a new category was designated.

PMID- 9611446
TI  - Dental hygiene self-regulation: an educational perspective.
AB  - Dental hygiene's pursuit of self-regulation has been impeded from its beginning
      by conceptual discrepancies. It is often confused with independent practice
      and/or other scope of practice issues, all of which cloud the real impetus: true
      professional status. The authors suggest this confusion could be addressed by the
      educational system. Students in schools offering education to future
      professionals must have an opportunity to gain insight into the political
      environment of their respective fields in addition to acquiring the theory and
      skills designed to make them clinically proficient. Through increased awareness
      of issues related to governance, they will be able to make informed decisions
      about matters affecting their chosen profession. From the outset, the objective
      of this investigation was to unveil some of the common misconceptions about self
      regulation held by students of dental hygiene and dentistry. Following a review
      of the literature, 11 of the most recurrent points of confusion were incorporated
      into a true/false survey. The survey addressed the following issues as they
      relate to dental hygiene self-regulation: ability to practice independent of
      dentists' supervision, ability to diagnose dental caries, scope of practice
      expansion, dissolution of the "dental team", compromised client safety and
      increased income-generating potential. The survey was distributed to dental
      hygiene and dentistry students across Canada. The results indicate a general lack
      of understanding of the concept of self-regulation among the Canadian dental
      hygiene and dentistry student population.

PMID- 9611448
TI  - Mobile oral hygiene services.

PMID- 9611447
TI  - Crowns all around.

PMID- 9611449
TI  - Dental management of a heart transplant patient.

PMID- 9611450
TI  - A student research review of the mouthbreathing habit: discussing measurement
      methods, manifestations and treatment of the mouthbreathing habit.
AB  - Mouthbreathing as an oral habit is seldom discussed in detail and as a
      consequence has tended to be overlooked by dental professionals. This review
      paper is an in-depth look at the current research on the mouthbreathing habit.
      This report aims to inform the dental professional of the most current definition
      of mouthbreathing and the methods of measuring the habit, including both
      observational and quantitative techniques. The various factors that can cause a
      mouthbreathing habit, such as asthma, allergies and enlarged glandular tissue,
      are discussed in detail. A review of current data on the skeleto-facial, dental
      and gingival changes that occur in mouthbreathing individuals is given, with the
      intention of raising the awareness of dental professionals to the special needs
      of these patients.

PMID- 9611451
TI  - Positioning for clinical dental hygiene care. Preventing back, neck and shoulder
      pain.

PMID- 9611452
TI  - Dental hygiene students' attitudes toward treating individuals with disabilities.
AB  - In the past, studies have been conducted to determine dental and dental hygiene
      students' attitudes toward the disabled following their clinical experience. The
      purpose of this study was to identify how dental hygiene students' attitudes
      toward treating clients with disabilities changed between the start and the end
      of their didactic and clinical rotation. Earlier research had examined dental
      hygiene students' attitudes toward individuals with disabilities following either
      a limited didactic and clinical course addressing disabilities or at the
      completion of their dental hygiene education. Few investigations had examined
      students' attitudes prior to and at the completion of a long-term course on
      clients with disabilities. The aim of this investigation was to determine if a
      one-year clinical and didactic course addressing various disabilities would
      result in a significant change in the students' attitudes and comfort level when
      treating clients with disabilities. The survey researched the attitudes of 18
      senior dental hygiene students in the special care clinic at Baylor College of
      Dentistry, Texas. The students received a pre- and post-modified survey of the
      "Dental Students' Attitudes Toward the Handicapped Scale" and were asked to rank
      their responses from strongly agree (5) to strongly disagree (1). The following
      areas were assessed: Group 1 (Positive Perceptions of Educational Training);
      Group 2 (Negative Attitude Toward Treating Persons with Disabilities); Group 3
      (Providing Dental Services); Group 4 (Negative Perceptions of Educational
      Training); and Group 5 (Comfort Level when Treating Persons with Disabilities).
      There was a significant improvement in the students' attitudes in Groups 1, 2 and
      4 with p-values for the questions in these groups ranging between p < 0.001 to p
      < 0.05. In Group 3, only two out of the five questions yielded a significant
      change in attitude, p < 0.001 to p < 0.01. Following the rotation, when asked
      about their comfort level in treating clients with disabilities (Group 5), the
      students reported being comfortable treating persons with autism p < 0.01,
      cerebral palsy p < 0.05, quadriplegia and paraplegia p < 0.05.

PMID- 9611453
TI  - Community practise in action.

PMID- 9611454
TI  - Ridge augmentation with guided bone regeneration and GTAM case illustrations.
AB  - The principle of Guided Bone Regeneration (GBR) can be used for Ridge
      Augmentation. These case illustrations describe the technique using Autogenous
      Cortico-Cancellous Bone Grafts and stabilization with Miniscrews and placement of
      a GTAM Barrier Membrane. Nyman et al (1990) published the first report of
      enlargement of a reduced alveolar ridge. Becker & Becker, Jovanovic, Buser et al
      have documented successful regeneration of such ridges. A study by Lang et al
      established that: 1. An undisturbed healing period of at least six months is
      required for optimal bone regeneration. 2. Smaller defects (less than 70 mm.3)
      regenerate almost completely. 3. Larger defects (greater than 90 mm.3) regenerate
      90-93 percent and bone grafts may enhance success in larger defects. 4. Premature
      membrane removal will result in incomplete regeneration. Buser et al have
      described the technique of GBR in detail. They found the creation and maintenance
      of a secluded space is essential for successful outcome with GBR procedures. This
      space allows for the in growth of osteogenic cells so that bone regeneration is
      undisturbed by competing non-osteogenic soft tissue cells. Space-making defects
      such as extraction sockets are simple to treat, but localized ridge augmentation
      may be difficult because the membrane is not supported by bony walls. E-PTFE
      membranes have been reinforced with titanium struts and mini screws have been
      developed as a way of dealing with membrane collapse. Buser et al began to
      utilize autogenous bone grafts to support the membrane and to act as an
      osseoinductive scaffold for bone regeneration. They utilized a cortico-cancellous
      block graft in the centre of the augmentative area with smaller chips to fill in
      the periphery. The cortical portion of the graft re-establishes the buccal cortex
      and the cancellous portion is placed against the host bone. The host bone is
      perforated to open the marrow spaces. Placement of membrane protects the bone
      graft (up to 50 percent of grafted bone is lost through resorption in
      augmentation procedures where membrane is not used).

PMID- 9611455
TI  - The role of the dental hygienist as change agent.

PMID- 9611456
TI  - The dental hygienist and the senior client.

PMID- 9611457
TI  - Hospice care.
AB  - Hospice of Peel is a community-based hospice serving a population of between 750
      800,000. Hospice care evolved to meet the needs of the terminally ill. It can,
      and does, take many forms, as you will see in the brief case scenarios detailed
      below. The individuals and situations described are real and typical of day-to
      day-hospice care in a large urban environment. Both the sick and their families
      are in need of support and assistance to enable them to cope during this time of
      crisis in their lives. Increased awareness of hospice care is resulting in more
      and more people with a life-threatening or terminal illness and their families
      turning to hospice care.

PMID- 9611458
TI  - Status of diagnostic techniques to detect progressive periodontitis.

PMID- 9611459
TI  - Ethics case study.

PMID- 9611460
TI  - Osteoporosis and alveolar bone loss.

PMID- 9611461
TI  - Dental hygienist provides mobile dental hygiene services.

PMID- 9611462
TI  - Management of the patient with mental retardation: a case report.
AB  - During the course of their careers dental professionals frequently interact with
      individuals presenting with mental retardation. In order to provide the best
      possible quality of care they should be aware of the etiology of mental
      retardation, the medical and dental conditions associated with this disability,
      and the services which can be incorporated into a treatment plan focused on
      improving the oral health for these individuals. This article identifies basic
      information dental professionals need to know when treating people with mental
      retardation, as well as describing a case report of the dental hygiene services
      that were provided to a patient presenting with this disability.

PMID- 9611463
TI  - Oral health: Mozambique's response to the challenge.

PMID- 9611464
TI  - Dental hygiene: challenges and opportunities for the millennium.
AB  - This paper was originally presented as the Keynote Speech at the ODHA Annual
      Spring Meeting, Toronto, May 1, 1997. The author has drawn on her lengthy
      involvement with the dental hygiene profession, including as a clinician,
      educator, researcher, and president of the Canadian and Ontario Dental
      Hygienists' Associations and the International Federation of Dental Hygienists.

PMID- 9611465
TI  - A two centre study to determine differences in the prescription of posterior
      bitewing radiographs between Manchester (U.K.) and Indianapolis (U.S.A.).

PMID- 9611466
TI  - A comparative study of the selection criteria and diagnostic yield in panoramic
      radiography for patients attending Manchester and Indianapolis dental hospitals.

PMID- 9611467
TI  - A study to determine and assess the diagnostic quality of bitewing radiographs
      taken by two methods: using paper bite tags and using a proprietary film holder.

PMID- 9611468
TI  - An extra molar?: an unusual artifact produced on a panoramic radiograph.

PMID- 9611470
TI  - Adjunctive orthodontic treatment of periodontally involved teeth: case reports.
AB  - Elongated and spaced incisors are common in patients suffering from severe
      periodontal disease. Intrusion and uprighting of incisors might be the logical
      solution for this problem. This article describes a team approach to treatment
      planning for adult patients with severe localized periodontitis accompanied by
      marginal bone loss and spacing and elongation of incisors. The treatment involves
      the combination of periodontal treatment, orthodontic intrusion, and prosthetic
      therapy. Controlled intrusion in two patients led to a decrease in the clinical
      crown length, better access for oral hygiene procedures, better gingival form,
      and a more suitable distribution of occlusal forces.

PMID- 9611469
TI  - Saucer-shaped cavity preparations for posterior approximal resin composite
      restorations: observations up to 10 years.
AB  - OBJECTIVE: This clinical trial aimed at studying the long-term performance in
      routine clinical practice of saucer-shaped Class II resin composite restorations.
      METHOD AND MATERIALS: Fifty-one preparations were completed and filled with
      either of two light-cured posterior composites by seven dentists of the Public
      Dental Service. The restorations were evaluated annually, using the US Public
      Health Service criteria, bitewing radiographs, and dies based on replica
      impressions. At the final evaluation, the recall rate was 100%. RESULTS: After a
      mean of 7.2 +/- 1.3 years of service (censored maximum of 9.6 years), 70% of the
      restorations were acceptable for continued use. Caries and technical deficiencies
      were the main causes of failure. CONCLUSION: The saucer configuration, by
      respecting and utilizing inherent properties of the resin composites, spares
      sound dentin and is preferable to the box preparation.

PMID- 9611471
TI  - Effect of differing resin luting systems on fracture resistance of teeth restored
      with dentin-bonded crowns.
AB  - OBJECTIVE: This study investigated the effect of differing bonding and luting
      system combinations on the fracture resistance of teeth restored with dentin
      bonded all-ceramic crowns. METHOD AND MATERIALS: Standardized preparations were
      carried out on five groups, each of 10 sound, unrestored, maxillary premolar
      teeth. Ceramic crowns were constructed, their internal surfaces were etched with
      hydrofluoric acid, and the crowns were placed with the following dentin bonding
      and resin-based luting system combinations: group A, Mirage ABC and Mirage FLC;
      group B, Metabond luting material; group C, All-Bond 2 and Duo-link; group D,
      Scotchbond MP Plus and 3M Indirect Porcelain Bonding Kit; and group E, All-Bond 2
      and 3M Indirect Porcelain Bonding Kit. The restored teeth were loaded in
      compression at 1.0 mm/min. RESULTS: Mean fracture loads of 0.77 kN, 0.81 kN, 0.71
      kN, 1.24 kN, and 1.03 kN were recorded for groups A, B, C, D, and E,
      respectively. Statistical analysis indicated that the mean fracture resistance of
      the restored teeth of groups D and E was significantly greater (P < .05) than
      that of the other three groups. CONCLUSION: The fracture resistance of dentin
      bonded crowns used in this laboratory study was dependent on the bonding and
      luting systems used.

PMID- 9611472
TI  - Stain removal efficacy: an in vitro evaluation using quantitative image analysis.
AB  - OBJECTIVE: This study developed a computer image analysis technique as a
      quantitative means to measure changes in dental stain after brushing with various
      dentifrices. METHOD AND MATERIALS: Enamel specimens with naturally occurring
      mature stain were cut from bovine incisors. The specimens were subjected to in
      vitro toothbrushing with one of the four tested groups, consisting of two
      dentifrices that make claims of stain removal (Aquafresh Whitening and Rembrandt
      Sensitive), a regular dentifrice, (Aquafresh Triple Protection), and water.
      Digital images of stain specimens were recorded under standardized lighting
      conditions and analyzed with an image analysis software. The area-intensity stain
      determinant, which accounted for the reflected intensity and the corresponding
      areas of stain, was computed. Stain removal efficacy was calculated based on the
      difference in area-intensity stain determinant before and after brushing.
      RESULTS: Brushing with any of the tested dentifrices removed more stain than did
      brushing with water alone. The finding that brushing with a regular dentifrice
      resulted in higher stain removal efficacy than brushing with water seems to
      indicate a role for abrasivity. Aquafresh Whitening had a higher stain removal
      efficacy than did Rembrandt for the removal of mature calcified stain used in
      this study. However, there were certain stains that none of the dentifrices
      removed. CONCLUSION: Computer image analysis provides an objective and
      quantitative measurement to distinguish in vitro stain removal efficacy of
      dentifrices.

PMID- 9611473
TI  - Anterior esthetic rehabilitation of all-ceramic crowns: a case report.
AB  - A patient had a serious esthetic problem: One maxillary central incisor was
      discolored and the other was malpositioned and fractured. The fabrication of two
      all-ceramic crowns fulfilled both functional and esthetic objectives.

PMID- 9611475
TI  - Familial occurrence of mesiodentes with unusual findings: case reports.
AB  - Supernumerary teeth are common and can occur throughout the oral cavity.
      Molariform supernumerary teeth in the maxillary central incisor area have rarely
      been reported. This article reports the presence of mesiodentes in two siblings,
      one of whom exhibited an unusual molariform mesiodens. The clinical and
      radiographic appearance of the anomalies and treatment modalities are discussed.

PMID- 9611474
TI  - Comparison of the clinical effects of subgingival application of metronidazole
      25% gel and scaling in the treatment of adult periodontitis.
AB  - OBJECTIVE: Control of subgingival plaque is of paramount importance in the
      treatment of periodontal diseases. The role of subgingival sustained-release
      antibiotic therapy needs elucidation. A single-blind clinical trial was carried
      out in 13 patients with adult periodontitis to compare the effects of subgingival
      application of metronidazole dental gel with those of subgingival scaling. METHOD
      AND MATERIALS: A split-mouth design was used so that each patient received all
      treatments simultaneously. Randomly selected quadrants were treated with
      application of 25% metronidazole gel, subgingival scaling, or a combination of
      scaling and gel application. The remaining quadrant in each patient was left
      untreated as a control. RESULTS: All three treatments were effective in
      significantly reducing Plaque Index, Gingival Index, and bleeding on probing over
      the 14-week observation period. No statistically significant differences were
      found between scaling alone and combined treatment. Scaling and combined
      treatment were better than metronidazole. Metronidazole produced transient
      effects, best noted during the first 4 weeks after treatment. No additive effect
      of metronidazole was noted in the combined treatment. At week 14, only combined
      treatment sites and scaled sites showed statistically greater probing depth
      reduction than control sites. CONCLUSION: For the treatment of mild-to-moderate
      adult periodontitis, subgingival scaling alone is as effective as the combination
      of scaling and antibiotic therapy.

PMID- 9611476
TI  - All-ceramic crowns on modified CeraOne abutments: a case report.
AB  - Single-tooth implants were used to replace congenitally absent maxillary lateral
      incisors in a 17-year-old patient. The inclination of the alveolar process caused
      a severe discrepancy between the axes of the planned implant and the crown. To
      avoid the need for a labial screw opening in the crown or labial overcontouring,
      a CeraOne abutment of the Branemark system was modified by selective grinding in
      the dental laboratory. Individual all-ceramic crowns were fabricated with the
      Celay In-Ceram system.

PMID- 9611477
TI  - Does your dental blue light have hot spots?

PMID- 9611479
TI  - Should e-mail be documented?

PMID- 9611478
TI  - Medicare billing: ignorance is not a defense.

PMID- 9611480
TI  - For your patients: recognizing eating disorders.

PMID- 9611481
TI  - Pharmacologic management of hypertension. Choosing an initial therapy.

PMID- 9611482
TI  - Dyslipidemia in diabetes. A comprehensive analysis.

PMID- 9611483
TI  - The right angle. Otitis media and infant feeding position.

PMID- 9611484
TI  - Weight management on either side of the scale. Pharmacologic principles.

PMID- 9611485
TI  - A look ahead. Third-generation antihistamines.

PMID- 9611486
TI  - One nurse's story.

PMID- 9611487
TI  - Self-administered epinephrine: a guide.

PMID- 9611488
TI  - Breaking bad habits.

PMID- 9611489
TI  - Treating fecal incontinence. Restoring self-esteem in your elderly patients.

PMID- 9611490
TI  - To each his own.

PMID- 9611491
TI  - Pediatric infectious disease: updates on three top offenders.

PMID- 9611492
TI  - Videoconferencing: practical advice on implementation.
AB  - Videoconferencing provides a useful tool for improving information flow, with
      clinical, educational and administrative uses being particularly relevant to
      rural and remote Australia. This paper describes the range of possible uses for
      computer-based videoconferencing and describes the authors' experience in
      delivering rural medical education in North Queensland via videoconference.
      Principles that ensure successful videoconferencing are outlined and are
      applicable to a variety of formats and uses. They include the need to keep it
      simple, the importance of thorough preparation, and ensuring that education
      drives technology, rather than the converse.

PMID- 9611493
TI  - Correlates of condom use and attitudes to condoms and AIDS in a group of Darwin
      women.
AB  - This study investigated the use of condoms, attitudes to condoms and correlates
      of these in women in Darwin, Northern Territory, Australia. A survey using a
      Condom Attitudes Scale was administered to a convenience sample of 160 women.
      With regular partners, these women had a low level of use of condoms, with a
      somewhat higher level of use with casual partners. Their perceived risk of Human
      Immunodeficiency Virus and other sexually transmitted diseases was not strong.
      These women's attitude towards the condom was reasonably positive. The major
      factor that correlated with attitudes to condoms was the type of relationship
      with a partner. This paper demonstrates the need for health professionals to
      continue to promote condom use among women.

PMID- 9611494
TI  - Rates of dental service provision between capital city and non-capital locations
      in Australian private general practice.
AB  - Variations in service provision between geographical locations may be associated
      with factors such as imbalances in the availability of health services. The aim
      of this analysis was to examine differences in dental service provision between
      capital city and non-capital locations. Data were used from a survey collected in
      1993/94 from a random sample of Australian dentists, providing 817 responses (a
      response rate of 74%). Dentists from capital city locations comprised 71.8% of
      responding private general practitioners. Significantly more services per visit
      (Mann-Whitney, P < 0.05) were provided at capital city locations (mean = 2.16,
      95% CI = 2.08-2.24) compared to non-capital locations (mean = 1.84, 95% CI = 1.74
      1.94). Controlling for age of patient, insurance status and visit type, capital
      city locations included significantly higher rates of service per visit (P <
      0.05) for adult dentate patients (rate ratios, 95% CI) of diagnostic (1.17, 1.09
      1.25), preventive (1.20, 1.09-1.32), periodontal (2.71, 1.72-4.26), and crown and
      bridge (1.25, 1.03-1.53) services, but lower rates of prosthodontic (0.80, 0.67
      0.94) services compared to non-capital locations. These findings indicate that
      compared to non-capital locations, capital city patients received care that was
      more orientated towards prevention and maintenance of teeth, rather than
      replacement by dentures.

PMID- 9611495
TI  - Rural youth: HIV/STD knowledge levels and sources of information.
AB  - Though it is recognised that a sound knowledge of HIV/STD transmission is
      insufficient on its own to ensure that young people practise safer sex, knowledge
      of this sort is a necessary prerequisite to safe sex behaviours. Research on the
      HIV/STD knowledge levels of young people has shown that, while they have high
      levels of HIV knowledge, they generally have little idea about the transmission
      of other STDs. Moreover, most of this research has been conducted with more
      accessible youth in large urban centres. The research reported in this paper
      focused on HIV/STD knowledge levels, awareness of safe and unsafe sexual
      practices, and the information sources accessed by 1168 young people living in
      small rural towns in Queensland, Tasmania and Victoria. As with mainstream youth,
      the participants in this study had high levels of HIV knowledge and very low
      levels of knowledge about the transmission of other STDs, their names and
      symptoms. Practical knowledge of the safety of sexual practices was good,
      although a number of students confused high risk practices with high risk groups.
      Students mainly accessed informal information sources such as parents, peers and
      magazines and took little advantage of more formal sources even when they were
      available in their towns. There were few gender differences in levels of
      knowledge; however, girls accessed more information sources and knew more names
      of STDs. The implications of these findings are discussed in relation to young
      people developing critical attitudes towards more informal sources, and the
      better use of more formal sources.

PMID- 9611496
TI  - Remote area health service delivery in central Australia: primary health care and
      participatory management.
AB  - This paper provides a description of initiatives and changes made in remote
      primary healthcare service delivery in Central Australia. These changes included
      the introduction of an orientation and Aboriginal cultural awareness program,
      revising the recruitment process to include communities in staff selection,
      developing policies and protocols to support practice, and increasing support for
      remote area staff through managers being out and about in remote areas. The
      change from centralised management to an increasingly decentralised participatory
      management model, and involving local communities and local staff in decision
      making, was initiated early in the change process and continues to be of prime
      importance. After 5 years of intensive effort, it is clear that despite these
      initiatives sustainable change has been elusive and some problems remain. Further
      change and development is necessary. A number of new initiatives are described,
      including a Menzies School of Health Research project that examines structural
      issues, which will provide direction for the future by providing better support
      for remote area staff and facilitating greater community participation.

PMID- 9611497
TI  - Methodological issues in medical workforce analysis: implications for regional
      Australia.
AB  - Medical workforce data have a profound impact on health policy formulation, but
      derived doctor population ratios (DPR) are often more relevant to plotting
      national trends than providing a detailed regional or local workforce
      perspective. Regional workforce data may be more useful if national approaches
      are augmented by local information. In developing a detailed workforce analysis
      for one region of Australia, the authors encountered several challenging
      methodological issues, including the accuracy of medical workforce databases,
      clarity of definition of community boundaries, interpretation of workforce
      definitions and the difficulty accounting for local community needs. This paper
      discusses the implications for regional workforce research.

PMID- 9611498
TI  - Age-standardised mortality and proportional mortality analyses of aboriginal and
      non-aboriginal deaths in metropolitan, rural and remote areas.
AB  - The study's aim was to assess how much of the variation in disease-specific
      mortality between metropolitan, rural and remote areas is specific to those
      diseases or reflects the all-cause mortality pattern. The ranges and variances of
      disease-specific standardised proportional mortality ratios between geographical
      areas were compared to those of the corresponding standardised mortality ratios.
      For most chapters in the International Classification of Diseases, the ranges and
      variances of the standardised proportional mortality ratios were less than 40% of
      those of the corresponding standardised mortality ratios. Only a small proportion
      of the variation in mortality can therefore be attributed to a specific disease
      component; the remainder must be attributed to an underlying 'force of
      mortality'. Research, programs and policies addressing the socio-economic
      disadvantages of living in remote areas may lead to a greater improvement in
      mortality than those targeting specific diseases.

PMID- 9611499
TI  - Methadone in rural general practice: addiction or rehabilitation.
AB  - This article presents the reflections of a rural general practitioner who has
      been involved in the Victorian methadone program for some years. Its object is to
      highlight some perceived strengths and weaknesses in the Methadone Program,
      particularly as it operates in rural areas, and to suggest some ways in which it
      could be modified to provide better for the needs of opiate-dependent persons who
      live outside the major cities.

PMID- 9611500
TI  - Outcomes in rural obstetrics, Atherton Hospital 1981-1990.
AB  - Analysis of annual obstetric audit data collected over the decade 1981-1990 from
      the Atherton Hospital in far north Queensland provides evidence of safe obstetric
      practice provided by a group of non-specialist doctors in a rural community.
      During that period, there were 2883 deliveries with an overall perinatal
      mortality of 5.2/1000. There were 1974 public confinements (perinatal mortality
      5.1/1000) and 909 private confinements (perinatal mortality 5.5/1000). By
      including those perinatal deaths that occurred in public patients who were
      transferred because of intrapartum complications, such as premature labour or
      neonatal problems, the corrected perinatal mortality rate for the public patients
      was 9.6/1000, which compares favourably with rates for Queensland and the Far
      North Statistical Division in 1987 of 13.5/1000 and 16.9/1000, respectively. This
      was achieved with low intervention, as indicated by an overall Caesarean section
      rate of 13.0% (public 10.6%, private 18.3%) and an antenatal referral rate of
      less than 2% of patients from the hospital public clinic for delivery under
      specialist care.

PMID- 9611501
TI  - Psychological symptoms in rural road trauma victims.
AB  - There is limited research into the psychological aftermath for people who have
      experienced road accidents, especially outside major cities. This study by postal
      survey used the General Health Questionnaire-28, the Impact of Events Scale, the
      Post-Traumatic Stress Disorder Interview, and the Late Effects of Accidental
      Injury Questionnaire to assess the psychological effects on a sample of 80 people
      who had attended a hospital in a regional Australian centre following road
      accidents. Results showed that there were marked effects on many people and that
      these had not always been diagnosed or treated.

PMID- 9611502
TI  - Unmentionables.

PMID- 9611503
TI  - Identifying the risk factors for developing incontinence: can we modify
      individual risk?
AB  - Urinary incontinence (UI) is a common but often misunderstood problem. Newer
      treatments are being developed and examined, but prevention of incontinence
      rarely is addressed in the medical literature. This article reviews the current
      literature on risk factors for developing UI and raises the question, "Can
      patient education or nursing intervention reduce the incidence of incontinence by
      identifying and modifying risk factors?"

PMID- 9611504
TI  - Barriers to progress in urinary incontinence: achieving quality assessments.
AB  - Urinary incontinence is a major care problem in nursing homes. Despite
      legislation aimed at decreasing its incidence, minimal progress has been made to
      achieve this goal. Obtaining an accurate assessment about the level and pattern
      of incontinence will assist caregivers in developing plans to reduce it. This
      article identifies barriers the authors have encountered in obtaining accurate
      records in a research project and strategies implemented to overcome these
      barriers.

PMID- 9611505
TI  - A continence care approach for long-term care facilities.
AB  - Urinary incontinence (UI) is one of the most common reasons residents enter long
      term care facilities. A large number of long-term care residents with UI can be
      managed successfully when the problem is assessed and barriers to successful
      toileting are identified. This article describes an active program for managing
      UI in long-term care facilities using a multidisciplinary approach.

PMID- 9611506
TI  - Continence restoration in the cognitively impaired adult.
AB  - A large proportion of residents in long-term care has some degree of cognitive
      impairement, and urinary incontinence (UI) is more prevalent in demented than
      nondemented older people. This article highlights an approach to continence
      assessment and restoration in the cognitively impaired patient.

PMID- 9611507
TI  - The financial side of continence promotion.
AB  - Urinary incontinence (UI) is a tremendous problem in this country. Behavioral
      treatments often are considered first-line therapy, yet many nurses are not sure
      how to get paid for providing these services. This article provides an overview
      of the methods available for obtaining payment for nursing interventions that
      promote continence. Although the article focuses heavily on Medicare
      reimbursement, managed care and fee-for-service plans are mentioned. Payment
      issues as they pertain to various locations and both basic and advanced nursing
      preparation also are covered.

PMID- 9611509
TI  - Continence care pioneers: Thelma Wells, RN, PhD, FAAN, FRCN, and Joyce Colling,
      RN, PhD, FAAN. Interview by Priscilla R. Ebersole.

PMID- 9611508
TI  - Urinary incontinence in older adults admitted to acute care. The NICHE Faculty.
AB  - Nurses are in a key position to identify and treat urinary incontinence (UI) in
      hospitalized elders. This article reviews the consequences and etiologies of UI
      with an emphasis on the most common types of UI encountered in the acute hospital
      setting. Assessment parameters and care strategies are highlighted; a nursing
      standard of practice protocol also is included.

PMID- 9611510
TI  - Implementing undergraduate student learning in home care.

PMID- 9611511
TI  - Update on treatments for urinary incontinence.

PMID- 9611512
TI  - Diabetes education and care at home.

PMID- 9611513
TI  - Justice and home health aides.

PMID- 9611514
TI  - Living with diabetes.

PMID- 9611515
TI  - Assessing laboratory values: serum Na+, K+, and Ca+.
AB  - Three common electrolytes--sodium, potassium, and calcium--often are measured in
      home health patients. The nurse must monitor these laboratory values so that any
      abnormalities are detected early. Early detection and early treatment can prevent
      further complications for the homebound patient.

PMID- 9611516
TI  - New recommendations to diagnose and classify diabetes: important implications for
      home care.

PMID- 9611517
TI  - Principles of disinfection: Part 2.

PMID- 9611519
TI  - Congress and home health services: is any relief in sight?

PMID- 9611518
TI  - Drug-induced hypoglycemia in home care patients with diabetes.

PMID- 9611520
TI  - Diabetic wound and lower extremity disorder management.

PMID- 9611521
TI  - What is this condition? Noninfected olecranon bursitis.

PMID- 9611522
TI  - Monitoring the medications of clients with noninsulin-dependent diabetes
      mellitus.
AB  - Noninsulin-dependent diabetes mellitus (NIDDM) (type 2) affects 16 million people
      in the United States. To effectively monitor such clients in the home, a thorough
      knowledge of the medications used to control hyperglycemia is needed. Primary
      failure with monotherapy has been studied and found to occur within 6 years.
      Combinations of two drug classes now are used to control blood glucose levels.
      The home health care provider must be aware of the mechanism of action of the
      different classes of hypoglycemic agents to monitor treatment. This article will
      discuss the different agents, their mechanism of action, and the use of
      combination therapies.

PMID- 9611523
TI  - Improving home care. A survey on physician and nurse communication.
AB  - Home health care is growing, and phone calls between physicians and home care
      nurses are essential to successful home care patient management. This preliminary
      study analyzed several aspects of the physician and home health nurse telephone
      communication, including effectiveness, time expenditure, percentage of calls
      resolved by physicians, and documentation of phone contacts between 90
      medical/surgical physicians and six home health nurses in Cleveland, Ohio. The
      phone conversations involved 154 patient contacts during a 3-month period.
      Overall, we found 75% of the home calls were effective. Eighty-five percent of
      calls required 15 minutes or less for completion, 47% of nurse-generated calls
      were resolved by physicians, and 26% of calls were documented in the patient's
      medical record. Our results illuminated several aspects of home care
      communication amenable to improvement.

PMID- 9611524
TI  - A community health practicum model for baccalaureate nursing students.
AB  - This article describes the evolution of a practicum for baccalaureate nursing
      students in a Department of Veterans Affairs home care program. The model
      includes direct patient care, support to caregivers, and assessment and referral
      to community resources. Students also assess communities and conduct teaching
      projects to targeted populations.

PMID- 9611525
TI  - Caring for your gastric tube at home.

PMID- 9611526
TI  - Caregiver resources.

PMID- 9611527
TI  - Joint Commission on Accreditation of Healthcare Organizations. Complying with the
      Joint Commission's challenging home care standards.

PMID- 9611528
TI  - National Association for Medical Equipment Services. Certification helps home
      care reach new heights.

PMID- 9611529
TI  - Popularity of evidence based nursing amongst practitioners.

PMID- 9611530
TI  - Negotiating realistic and mutually sustaining nurse-patient relationships in
      palliative care.
AB  - This paper uses a literature review to question the proposition that nurses will
      be permitted to care for the psychosocial and spiritual needs of patients in the
      manner that is frequently presented as the nurses role. Second, it will explore
      qualities in nurse-patient relationships that can be not only helpful to those
      who are cared for but also can be a mode of sustenance to the nurse. Issues
      explored are the social construction of the nurse-patient relationship, reality
      checking, balancing emotional and cognitive functions in nursing, focus of
      nursing commitment, power issues, reciprocity and boundaries. Palliative care
      nursing will be referred to in relation to these themes as it is an area of
      nursing which highlights the increasing focus on psychosocial care. For this
      reason questions of what is realistic and sustainable for the nurse are of prime
      importance.

PMID- 9611531
TI  - The complexity of searching the literature.
AB  - The science of systematically reviewing literature has become a research process
      in its own right. The key word of course, is systematic. In the context of a
      systematic review this indicates that all possible sources have been
      comprehensively searched using a pre-defined search strategy designed to identify
      all relevant published and unpublished work. This paper illustrates the
      components of a comprehensive search, examines the yield of this approach and
      discusses the time and resource requirements for conducting the search. It uses
      as an example a recently completed systematic review. The paper goes on to
      discuss ways in which nurses can become more involved in conducting and using the
      results of good quality reviews.

PMID- 9611532
TI  - Disaster relief work: nurses and others in bushfire territory.
AB  - This paper describes one aspect of a study into the experiences in long-term
      healing of a community following the 1983 Ash Wednesday bushfire. Forty
      participants were interviewed, of whom 26 were residents and 14 disaster relief
      workers. The paper concentrates on the experiences of the latter, describing how
      they came to understand the bushfire affected the community and how they managed
      disaster work. For novices it was a profoundly difficult experience, for which
      they received little help and had to manage with whatever skill they drew on in
      their 'normal' working lives, mixed with a good deal of intuition. The paper
      suggests that health workers in vulnerable areas require preparation for a likely
      disaster; that 'outsiders' need to deal through existing community groups and
      individuals to gain access to those in need of their skills, and that they also
      require preparation for helping 'insiders' who are themselves victims of the
      catastrophe.

PMID- 9611533
TI  - Age-related hearing loss in the dependent elderly population: a model for nursing
      care.
AB  - Advancing nursing care through the implementation of evidence-based practice is a
      legitimate professional ideal. In reality there are many complex issues that need
      be addressed before such a goal can be achieved. This paper takes an intermediate
      step towards the realization of this aim in one aspect of continuing care nursing
      through the presentation of a procedural model. The presented model is designed
      to stimulate debate as to what could be, and arguably should be the role of the
      nurse in relation to meeting the auditory rehabilitative needs of dependent
      elderly patients. The model is based upon a published management model which
      outlines the auditory rehabilitative process within a psychosocial framework. The
      original model has been modified as a result of knowledge synthesis from a range
      of specialist disciplines including nursing. The Audiological Care Model for
      Nursing is intended to offer an accessible guide to this often neglected aspect
      of care.

PMID- 9611534
TI  - Liver transplantation: the death/life paradox.
AB  - Transplantation of organs has increased dramatically over the last 3 decades. The
      Australian National Liver Transplant Unit was established in 1985 at Royal Prince
      Alfred Hospital. Their first 5 years was reported in a paper in 1992 in which
      survival was defined as 'going home'. The study reported in this paper followed a
      3 year study with one woman who experienced a liver transplant in which survival
      had many dimensions, of which going home was not one. This post doctoral study of
      2 years extended the earlier work with one woman by exploring the experience with
      eight 'survivors'. It highlighted the paradox of facing life and death at the
      same time, which occurs when one has a terminal illness but is on a waiting list
      for a donor organ which could be life saving. Focus groups were used as the
      methodology while story telling within the group became the means by which
      individuals and the group recalled and made meaning of their experiences.

PMID- 9611535
TI  - Measurement of sleep and quality of life before and after coronary artery bypass
      grafting: a pilot study.
AB  - The aim of this study was to: (i) test different instruments that focused on
      sleep, quality of life and personal adjustment in order to evaluate the
      usefulness of these instruments in a larger study; and (ii) to describe self
      perceptions of sleep and life situation by patients who had undergone coronary
      artery bypass grafting (CABG). A one-group pre-test repeated post-test design was
      used. Six men aged between 51 and 70 years were interviewed, and 24 h
      polysomnographic recordings were performed before and after the operation. The
      interviews indicated disturbed sleep and changes in behaviour and mental state
      immediately postoperatively. Postoperatively the polysomnographic recordings
      revealed a significant decrease in mean duration of sleep, mean percentage of
      stage 3-4 sleep and mean rapid eye movement (REM) sleep. One month after surgery
      the quality of life was improved, while moderate anxiety and sensation of
      incisional pain persisted. The measurements used in this pilot study provide
      valuable information into the understanding of altered sleep, quality of life and
      personal adjustment following CABG.

PMID- 9611536
TI  - Relationships between demographic variables and family dynamics of childbearing
      families.
AB  - In this study relationships between demographic variables and family dynamics of
      childbearing families in Finland were studied. The sample was 160 urban families
      expecting their first or second child in the third trimester of pregnancy. One
      hundred and eighteen families participated in the study. The Family Dynamics
      Questionnaire (FDQ) and the Family Dynamics Measure (FDM) were used in this
      study. Most expectant parents reported their family was well-functioning. Mothers
      of higher socioeconomic status found more flexibility in their families than
      mothers of lower socioeconomic status. Fathers in families expecting their first
      baby reported more mutuality, role reciprocity and more stability than second
      time fathers. The findings contribute cues for public health nurses and midwives
      regarding parity, socioeconomic status and family dynamics to provide more
      specific family guidance during the transition to parenthood. Realistic
      information on the changes in family dynamics after childbirth should be given to
      pregnant parents.

PMID- 9611537
TI  - Ethical dilemmas concerning sexuality of elderly patients suffering from
      dementia.
AB  - This study endeavoured to clarify the ethical dilemmas concerning sexuality
      encountered by nurses caring for elderly patients suffering from dementia, and to
      assist the decision-making process of the nurses and staff who handle dilemmas of
      this nature. Many of the staff in geriatric institutions report difficulties,
      confusion, embarrassment and helplessness as well as negative responses and
      rejection when encountering sexual situations between patients of the same or
      different sex, patients and staff members or between patients and visitors.
      Embarrassment over sexuality is felt by staff members, visitors and family. This
      embarrassment may result in elderly patients being treated like children, and
      being separated from their partners. A response of this nature can provoke anger
      in the patients, sometimes leading to violence. The central dilemma on the
      subject of sexuality in a geriatric institution is the fact that staff are in
      conflict between the desire to protect the elderly patients and maintain their
      dignity and the patients' desire to fulfil their sexual needs. Since no single,
      definitive prescription can be provided for conduct acceptable to the staff, the
      patients and their families, it was decided to work with the staff on the basis
      of case studies to help them in selecting ways of coping.

PMID- 9611538
TI  - Development of a constipation risk assessment scale.

PMID- 9611539
TI  - Australia: international issues in nursing service delivery: a synopsis and
      critique of the future direction of healthcare services and nursing's role within
      it in Australia.

PMID- 9611540
TI  - "Sometimes you don't feel ready to be an adult or a mom:" the experience of
      adolescent pregnancy.
AB  - PROBLEM: To obtain a description of pregnant adolescents' responses to the
      preparation for motherhood class curriculum. METHODS: The design of this study
      was based in the anthropological tradition of qualitative research, ethnography;
      N = 36. FINDINGS: Within one category identified in this study, maternal role,
      three primary themes emerged: responsibility, respect, and reparation.
      CONCLUSIONS: The findings of this study indicate that for some adolescents,
      pregnancy implies a desire and an opportunity to heal childhood wounds if
      relevant psychotherapeutic interventions can be provided. Nurses can identify
      pregnant teens who are already suffering with depression and encourage them to
      seek counseling prior to the birth of their baby before they are experiencing the
      added stressors inherent in new motherhood.

PMID- 9611541
TI  - Attention-deficit/hyperactivity disorder: a neurodevelopmental approach.
AB  - TOPIC: Attention-deficit/hyperactivity disorder is frequently overdiagnosed when
      a complete evaluation by a knowledgeable clinician is not undertaken. Because of
      the recent negative media campaign regarding psychostimulant medication, it
      becomes more imperative that a thorough and accurate evaluation be completed
      before starting children and adolescents on psychostimulant medications. PURPOSE:
      To describe the neurodevelopmental perspective in the assessment and treatment of
      ADHD. SOURCES: Published literature and clinical experience. CONCLUSION: It is
      useful in practice to conceptualize the developmental path of children with ADHD
      not as disordered but as delayed, and to build on each child's strengths. The
      neurodevelopmental approach provides the child psychiatric nurse a child-focused
      framework for assessment and development of individualized interventions.

PMID- 9611542
TI  - Perceived self-care capabilities of abused/neglected and nonabused/non-neglected
      pregnant, low-socioeconomic adolescents.
AB  - PURPOSE: The purpose of this study was to determine whether abused and nonabused
      pregnant, low-socioeconomic adolescents differ in regard to perceived self-care
      capabilities. SAMPLE: The sample (N = 36) consisted of 18 abused/neglected and 18
      nonabused/non-neglected adolescents. DATA ANALYSIS: The adolescents' responses on
      the Denyes Self-Care Agency Instrument were analyzed to determine significant
      differences between the two groups regarding self-care agency. FINDINGS:
      Significant differences were found between the two groups in regard to perceived
      relative valuing of health and perceived attention to health. CONCLUSIONS:
      Although abused adolescents had a higher level of relative valuing of health and
      lower attention to health than their nonabused counterparts, findings show that
      both groups are capable of performing self-care and should be encouraged to do
      so.

PMID- 9611543
TI  - Atypical neuroleptics in children and adolescents.

PMID- 9611544
TI  - Communities in transition and construction of identity.

PMID- 9611545
TI  - Concept analysis: cultural competence.
AB  - To evaluate theory, concepts with that theory must be identified, analyzed and
      defined. The aim of this concept analysis of cultural competence is to clarify
      and differentiate the term as it is used in health care and nursing literature
      and to separate cultural competence from its measurement. Before the question of
      what is cultural competence can be answered, culture and competence--as separate
      terms--must be understood. Components of the cultural competence concept are
      identified along with its antecedents and consequences. Additionally, terms
      closely related to cultural competence are described and differentiated from the
      cultural competence concept. To add meaning to the analysis, a cultural
      competence model case and contrary case are supplied along with outcome measures
      and empirical referents for cultural competence. Finally, a concluding definition
      based on extensive review of literature sources such as archeology, anthropology,
      history, psychology, policy, criminal justice, occupational therapy, medicine,
      nursing, and education is provided.

PMID- 9611546
TI  - Caregiver characteristics and types of assistance provided by caregivers to
      minority women living with HIV/AIDS.
AB  - The incidence of HIV/AIDS has escalated among African American and Hispanic women
      in the United States and particularly in urban centers such as New York City. As
      a chronic illness, it is important to understand to whom minority women living
      with HIV/AIDS turn to for assistance and support. The purpose of this exploratory
      qualitative study was to identify the characteristics of informal caregivers and
      the types of assistance that they provide to minority women living with the HIV
      virus. Thirty one caregivers were interviewed using semi-structured and opened
      ended questions. Data analyses included the constant comparative method
      consistent with the grounded theory approach. A topology of two caregiver groups
      were identified, male companions and relative/girlfriend caregivers. Caregiving
      activities are described within each group in the areas of emotional support,
      child care, personal advisement, social welfare and financial assistance.
      Implications for practice and recommendations for further study are discussed.

PMID- 9611547
TI  - Utilization of folk/family remedies by community-residing African American
      elders.
AB  - The purpose of this study was to identify the range of folk/ family remedies used
      by African American elders to promote health. This was accomplished by obtaining
      self report information from a convenience sample of 200 African American elders.
      Participants resided in senior apartment complexes in metropolitan Baltimore.
      Fifteen categories of folk/family remedies were used routinely by African
      American elders to promote health or prevent illness. There were sixteen purposes
      identified for the categories of folk/family remedies.

PMID- 9611548
TI  - Privatizing higher education in Bangladesh: an American professor's involvement
      during the transition.
AB  - The topic of teaching abroad is a timely one in light of the increasing
      involvement of students, educators and industry professionals in international
      exchange programs. The author hopes that other educators, in particular, may
      benefit from the very personal insights brought by this paper into the early
      stages of experience of a professor who took on the challenge of a teaching
      assignment in Bangladesh during its significant period of transition from public
      to private higher education.

PMID- 9611549
TI  - Patient's perception of pain: comparison between Korean-American and Euro
      American obstetric patients.
AB  - This study explored the differences and similarities in the perception of pain
      reported between Korean-American and Euro-American obstetric patients, describing
      whether the different ethnocultural background of patients affected their
      perception of pain. Gate control theory provided the basis for the study. The
      theory of pain emphasizes the role of psychological variables in the perception
      of pain and behavioral responses to pain. The sample (N = 124) consisted of 67
      Euro-American and 57 Korean-American patients, who had delivered a baby within 12
      to 24 hours of the interview in a large community hospital in New York City. The
      results indicated that there were statistically significant differences in the
      quality of pain especially in affective type of pain experience and overall
      evaluation of pain while no significant differences appeared in the pain
      intensity in general between the two groups. Also, there were many interesting
      findings such as using own words in expressing pain, preferences in gender of
      baby, and childbirth training, or social support which reflected much cultural
      influences.

PMID- 9611550
TI  - A pitch for public policy.

PMID- 9611551
TI  - Changes in health status of elderly patients following hip replacement surgery.
AB  - This study investigated changes in health status following a total hip
      replacement among a convenience sample of 22 male and 23 female patients, all of
      whom had been suffering from hip dysfunction and associated arthritic pain and
      impaired mobility. Subjects were pretested in an orthopedic pre-admission clinic
      with the Arthritis Impact Measurement Scales questionnaire and were posttested
      with the same instrument 3 1/2 months after the initial contact and subsequent to
      hip replacement surgery. Analysis of pretest and posttest mean differences showed
      significant improvement in scores for pain and physical activity. No significant
      changes were demonstrated in the psychological and social domains of health
      status.

PMID- 9611552
TI  - Filial piety. A cross-cultural comparison and its implications for the well-being
      of older parents.
AB  - The purpose of this article is to compare and contrast the concept of filial
      piety in Chinese culture and American culture and to discuss the relationship
      between expectations of filial piety and the well-being of older adults. In both
      cultures, filial piety is a socially approved virtue and contains attributes of
      respecting, caring for, and loving the parents. The differences include:
      obedience versus confrontation of parents; limited versus unlimited
      responsibility to parents; and a difference in the concept of legitimate support.
      Based on previous literature, the relationship between the expectations of filial
      piety and parents' well-being was explored, and nursing implications were
      suggested. Nonetheless, there is no single intervention that could fit all
      clients from one culture. Nurses need to examine to what extent clients value
      their culture of origin.

PMID- 9611553
TI  - The relationship between loneliness, social support, and decline in cognitive
      function in the hospitalized elderly.
AB  - To determine the effects of preexisting levels of loneliness and social support
      on cognitive decline during hospitalization, 145 elderly subjects 65 to 92 years
      old without impaired cognition were tested for levels of loneliness, social
      support, and cognitive status on admission to an acute care hospital. Five days
      later, cognitive status was again measured in the remaining 86 patients.
      Loneliness was found to be inversely related to cognitive status on admission. In
      those with high loneliness scores on admission, cognitive status had improved
      significantly 5 days later. High social support was correlated with high
      cognitive status on admission and significant cognitive decline during
      hospitalization.

PMID- 9611554
TI  - Special care units for people with Alzheimer's disease. Only for the privileged
      few?
AB  - The number of Special Care Units (SCUs) for people with Alzheimer's disease (AD)
      in nursing homes have increased dramatically in the past 10 years. Despite the
      rapid increase in number of SCUs and the concern that most SCUs report higher
      costs than traditional nursing home units where residents with AD are integrated
      with cognitively intact residents, the evaluation of costs has been largely
      unsystematic and noncomparative. Studies are urgently needed to assess
      comparative costs so that administrators and policy makers can make informed
      decisions. This article reviews studies that examine the costs of care in SCUs
      and presents cost-related data comparing the outcomes of care for residents with
      AD on a SCU and on traditional units in one long-term care setting.

PMID- 9611555
TI  - Rethinking the obvious. A model for preventing constipation.

PMID- 9611556
TI  - Building community: developing skills for interprofessional health professions
      education and relationship-centered care.

PMID- 9611557
TI  - What methods do you use to make mealtime a pleasurable but efficient experience
      in your setting?

PMID- 9611558
TI  - Merging regulations and recommendations. How can the best outcomes be achieved?

PMID- 9611559
TI  - AIDS in older people. A literature review for clinical nursing research and
      practice.
AB  - Older Americans, 50 years of age and older, account for 10% of the 400,000
      reported cases of AIDS nationwide (Centers for Disease Control and Prevention,
      1994). the integrated literature review format in this article examines the
      published literature on HIV/AIDS in older adults. Most articles are case studies
      and reports, with only 17% having a research basis. The information reviewed
      indicates that older adults have different risk factors than younger populations
      for contracting HIV disease and a different pattern of disease progression. These
      differences create a need for knowledge of HIV infection and AIDS and its
      parameters in aging populations so nurses may provide both timely and appropriate
      care.

PMID- 9611560
TI  - Legalization of assisted suicide. A pilot study of gerontological nurses.
AB  - 1. Legalization of physician-assisted suicide poses serious challenges to the
      Code for Nurses of the ANA, particularly in the areas of self-determination and
      autonomy versus sanctity of life. 2. Nurses in this pilot study were divided in
      their support of legalization of physician-assisted suicide for all ages (46 in
      favor, 54 opposed) but showed stronger support for legalization when applied to
      the elderly (58 in favor, 42 opposed). 3. No demographic variables realized
      statistical significance toward attitudes on the legalization of physician
      assisted suicide or its legalization as applied to the elderly. 4. While
      supported conceptually, the actual practice of physician-assisted suicide was not
      supported by many who were in favor of legalization of physician-assisted
      suicide.

PMID- 9611561
TI  - Assessment and management of sleep disorders in the elderly.
AB  - Sleep disorders are major syndromes that can interfere with falling to sleep or
      maintaining sleep, or produce excessive daytime sleepiness. Sleep disorders are
      rarely diagnosed in the elderly due to age-related changes in sleep patterns.
      Gerontological nurses can assist the elderly client to achieve improved sleep
      through increased awareness of sleep disorders, related assessment tools, and
      interventions.

PMID- 9611562
TI  - Nursing home dementia care units. Providing a continuum of care rather than aging
      in place.
AB  - Experience from the first 24 months of a new Dementia Special Care Unit is
      presented with an emphasis on admission and discharge criteria, length of stay,
      and reasons for discharge. Maintaining residents with moderate functional
      abilities on a Special Care Unit is examined relative to relocation stress, aging
      in place, and staff needs. The benefits of providing a continuum of dementia care
      and the risk of potential harm of frequent intra-institutional moves are
      discussed.

PMID- 9611563
TI  - Aging and alcohol.

PMID- 9611564
TI  - Addressing hypersexuality in Alzheimer's disease.

PMID- 9611565
TI  - Nurses know that to change behavior, more than information is necessary. Have you
      found any motivational strategies that are particularly successful?

PMID- 9611566
TI  - Share your pearls. H.A.M.--Hygiene, Air and Mobility.

PMID- 9611567
TI  - School nurses and ethical dilemmas: are schools short on ethics?

PMID- 9611568
TI  - Advance directives and do not resuscitate orders: nurses' knowledge and the level
      of practice in school settings.
AB  - A descriptive, correlational study was conducted among school nurses to ascertain
      their knowledge of Advance Directives (ADs) and Do Not Resuscitate (DNR) orders,
      current AD and DNR practice in the school setting, and personal AD and DNR
      attitudes and plans of study respondents. A convenience sample of practicing
      school nurses was surveyed using an author-designed instrument. Results indicated
      a need to increase knowledge regarding ethical principles and advance directives.
      Eleven percent of the respondents reported school district policies in place
      regarding advance directives/DNR orders. Seventy-eight percent of respondents
      indicated they have no personal advance directives in place, but 76% would not
      wish to be resuscitated when facing terminal illness. These results suggest
      ambiguity regarding issues of death and dying.

PMID- 9611569
TI  - School health nursing services progress review: report of 1996 national meeting.
AB  - This is a report of the outcomes of an invitational meeting convened in 1996 by
      the Division of Adolescent and School Health at the Centers for Disease Control
      and Prevention (DASH/CDC) and the National Center for School Health Nursing,
      American Nurses Association. Participants reviewed progress made on seven
      critical needs identified in 1994 at the School Health Nursing Services:
      Exploring National Issues conference. Priority actions were updated, consensus
      was reached for specific strategies to move toward achievement of goals, and
      organizations and agencies were suggested to assume leadership. Participants and
      current membership of the National Nursing Coalition for School Health are
      listed. Collaborative partnerships are encouraged to assist school nurses in
      meeting the school-related health needs of students.

PMID- 9611570
TI  - Promoting mental wellness in children and adolescents through positive coping
      mechanisms.
AB  - Children and adolescents frequently experience stressful events such as moving to
      a new city, divorce of parents, or peer pressure. Parents may be unavailable or
      unable to model effective coping mechanisms for their children. Without adequate
      coping mechanisms children frequently are unable to adapt to a stressor; thus a
      crisis develops. School nurses and other school professionals are in a key
      position to help young people handle stressful life events and prevent a crisis.
      This paper reviews stress and suggests techniques to assist children and
      adolescents to identify and utilize coping strategies while in crisis.

PMID- 9611571
TI  - A survey of computer technology utilization in school nursing.
AB  - Computer technology offers a solution to problems associated with paper-based
      health records. The purposes of this descriptive study were to identify the
      utilization of and support for computer technology in managing student health
      data and documenting school nurse practice. Findings from a sample of school
      nurse respondents to the Computer Technology and School Nursing Survey (CTSNS)
      indicated that of the 65% that used computers, nearly two-third used computers
      for three years or less. Although there was an increase in computer use when
      compared with an earlier study, more training, financial support, and research
      are needed for optimal utilization of computer technology.

PMID- 9611572
TI  - Antiretroviral therapy for pediatric and adolescent HIV.
AB  - As the number of children infected in the HIV epidemic increases, the school
      nurse can play an important role in ensuring that these children receive
      comprehensive health care. Compliance with following an immunization program for
      HIV-infected children is a potential problem for various reasons. Many of these
      children come from homes where the mother also has HIV/AIDS. She is likely to be
      involved in keeping her family together, caring for her own health needs, and
      meeting financial and social needs of her family. Access to health care may be
      limited. The majority of vaccines administered within the first few months of
      life are parenteral and consist of inactivated antigens. Children or infants who
      are immunosuppressed may be unable to respond to the immunogen, thus rendering
      them susceptible to many infectious diseases. Heterosexual transmission and
      pregnancy compound the problems of HIV/AIDS (Flynn, 1994). Compliance following
      an immunization schedule becomes a greater challenge when working with the
      adolescent population. Parents may not understand that the risk of receiving
      vaccine, MMR for example, is less than the risk of severe complications
      associated with the diseases themselves. Coordination of care between the child,
      parent, and school district personnel is imperative to minimize the risk of
      further health-related problems of the HIV-infected child. Encouraging regular
      immunizations can decrease the child's susceptibility to infection, and
      administering medications properly can enhance the benefits of the drug therapy.
      An excellent resource for answering questions of school nurses related to
      HIV/AIDS is the National Pediatric and Family HIV Resource Center; contact Elaine
      Gross, R.N., M.S. at 1-800-362-0071.

PMID- 9611573
TI  - Utilizing standards of nursing practice for effective school nursing management.
AB  - This article describes the relevance of utilizing the Roles and Standards of
      School Nursing Practice in managing school health services systems effectively.
      One significant standard described is Program Management. This standard falls
      under the role of Planner and Coordinator of Client Care. By utilizing standards
      of practice to build and review school nursing practice, readers will be able to
      validate their significant role in supporting student success and management of
      school health programs.

PMID- 9611574
TI  - Spirituality through centering prayer in school nursing.
AB  - The experience of intuition in a school setting contributes to a positive outcome
      for a young girl who suffers a playground injury. Intuition and spirituality are
      linked. Through the development of one's spirituality, intuitive thoughts are
      experienced. Centering prayer is presented as a technique to develop an awareness
      of the spiritual dimension. Three variations of centering prayer are described to
      help individuals develop their spirituality. Developing an awareness of the
      spiritual dimension opens the way for intuitive thoughts to enhance clinical
      nursing competence and all other aspects of living.

PMID- 9611575
TI  - Understanding change in clinical nursing practice.
AB  - The present paper employs a poststructural framework to explore the construction
      of change in clinical nursing practice, as portrayed in nursing literature. In it
      a critique of two specific bodies of literature is offered: that which deals with
      the 'abstract' conception of change (but which is heavily influenced by
      organizational discourses) and that which describes changes in the clinical
      setting of critical care nursing practice. It is argued that the discursive
      constitution of change that is revealed in this analysis disadvantages clinical
      nurses. Because the context in which change occurs is largely unacknowledged,
      clinical nursing practice, as experienced and understood by nurses, is also
      marginalized. Change in clinical practice is under-researched, and such inquiry
      should be undertaken from the perspective of nurses themselves, and requires an
      exploration of the discursive context of nursing work.

PMID- 9611576
TI  - Nursing and motherhood constructions: implications for practice.
AB  - The present paper addresses the relationship between community based child health
      nursing services and social constructions of motherhood within Australia during
      the 1920s. Following the First World War, child health nursing services (then
      generally known as infant welfare or child welfare services) were established in
      all Australian states. The focus of the paper is mainly upon the development of
      the Tasmanian child health service, with some reference to similar services in
      other states. Within two decades of their establishment, most child-bearing women
      in Tasmania were in contact with child health services and this apparent success
      meant that, thereafter, women in Tasmania cared for their children under the
      'expert' guidance of nurses. As the 1920s progressed, child health nurses
      increasingly promoted one particular, and ultimately extremely influential,
      construction of motherhood, 'scientific motherhood', based upon the philosophy of
      Dr Truby King. I argue that an understanding of how nursing services have
      historically reinforced and promoted ideological constructions of motherhood
      enhances the practice of present day nurses working with women. This argument is
      supported by reference to present day nursing practice in relation to postnatal
      depression.

PMID- 9611577
TI  - Caring through a reflective lens: giving meaning to being a reflective
      practitioner.
AB  - Who is a reflective practitioner? It is assumed that a reflective practitioner is
      someone who views and responds to practice through an appropriate reflective
      lens. The present paper is a reflective account that gives meaning to being a
      reflective practitioner within everyday practice whereby the reflective lens is
      structured through the Burford Nursing Development Unit (NDU) Model: Caring in
      Practice.

PMID- 9611578
TI  - Ethics and nursing research: meeting the needs of indigenous peoples.
AB  - Identifying an appropriate ethical approach to guide research with historically
      exploited peoples, indigenous or disadvantaged, places the nurse researcher in an
      unenviable position. Conventional ethical procedures may be appropriate for the
      predominant society and academia; however, these have the potential to further
      disable the aspirations and integrity of those who are the focus of the research.
      The present paper examines a number of ethical guidelines designed by and in
      collaboration with Australia's indigenous peoples. The guidelines of the National
      Health and Medical Research Council (1991) are used as the benchmark for the
      discussion as these are the most frequently referred to and used in the approval
      of nursing and health research. The concepts and approaches discussed may be
      considered in other contexts where nursing research is conducted with or about
      historically disadvantaged peoples.

PMID- 9611579
TI  - From angels to handmaidens: changing constructions of nursing's public image in
      post-war Britain.
AB  - The public image of nursing is an important barometer of how the profession is
      valued in society. Recent research into images of nurses tends to use content
      analysis to substantiate claims that the mass media misrepresent the profession,
      perpetuating outmoded conceptions of nursing work. Such a strategy treats the
      nature of nursing itself as unproblematic, an object to be more or less
      accurately 'represented'. But these are assumptions that need to be questioned.
      The systems of belief and value that produce representations of nursing both
      reveal and constitute the institutional practices that regulate nursing as a
      profession, which in turn shape the material form and substance of
      representational constructs. Drawing on fictional and factual popular and
      official representations of nursing and nursing work on film, television and in
      recruitment literature, it is argued that although nursing was consistently
      constructed as 'women's work' for much of the 20th century, a noticeable shift is
      perceivable in the status of nursing's public image between the late 1930s and
      early 1970s.

PMID- 9611580
TI  - Organizing context: nurses' assessments of older people in an acute medical unit.
AB  - The paper presents findings from a study of how older people are assessed and
      cared for in an acute medical unit. The aim of the study was to reconsider
      nurses' assessment practices in relation to organisational context. Drawing
      together ethnographic methods with discourse analysis, the study develops an
      approach to studying nurses' assessment practices and aims to demonstrate that
      nurses go beyond entering their relationships with patients as individuals.
      Rather, nurses' assessments of patients can be considered as processes of
      alignment that help nurses accomplish complicit managerial and medical
      objectives, and shape their own identities.

PMID- 9611581
TI  - The experience of doctoral learning within a major research project.

PMID- 9611582
TI  - Our Healthier Nation.

PMID- 9611583
TI  - Occupational health audit.

PMID- 9611584
TI  - Education for a specialist future.

PMID- 9611585
TI  - Managed care. A view from down under.

PMID- 9611586
TI  - The eve of the release of the Green Paper.

PMID- 9611587
TI  - Yvonne Moores. Interview by Tom Keighley.

PMID- 9611588
TI  - Research strategy.

PMID- 9611589
TI  - A career in management.

PMID- 9611590
TI  - Self-esteem.

PMID- 9611591
TI  - RCN/LPNS/nursing management lectures.

PMID- 9611592
TI  - Ethnic lessons.

PMID- 9611593
TI  - The carrot beats.

PMID- 9611594
TI  - Spiritual care.

PMID- 9611595
TI  - The rocking horse risk.

PMID- 9611597
TI  - Jacqueline Mather. Interview by Tom Keighley.

PMID- 9611596
TI  - Shifting the responsibility.

PMID- 9611598
TI  - Valuing your staff.

PMID- 9611599
TI  - Finance and accounting for nurses. Part 4.

PMID- 9611600
TI  - Guilt by association.

PMID- 9611601
TI  - World Council for Enterostomal Therapy.

PMID- 9611602
TI  - Tracking how well you keep on track.

PMID- 9611603
TI  - Paternalism in healthcare decision making.
AB  - Paternalism is described as a dominant attitude of one over another. It was
      widely practiced years ago because clinicians were usually expected to make the
      best decision for the patient. Modern healthcare, with its many technically
      advanced diagnostic and treatment modalities complicates decision making. The
      trend legally and morally is to include the patient in the decision making
      process because patients are increasingly informed and able to participate in the
      decision making process. However, the risks of paternalism continue to be a
      debatable issue in healthcare. The purpose of this article is to describe types
      of paternalism, to present justification for paternalism, and to offer a case
      study to illustrate the struggle that occurs when decisions made by clinicians
      collide with decisions made by patients.

PMID- 9611604
TI  - Squamous cell carcinoma arising from a nonhealing wound and osteomyelitis treated
      with Mohs micrographic surgery: a case study.
AB  - The treatment of choice for squamous cell carcinoma arising from chronic ulcer at
      the lower extremity has traditionally been amputation. Recently, Mohs
      micrographic surgery has been used as a limb-saving option in selected patients.
      One of these patients, a 69 year-old white male, presented with a two-year
      history of a progressive non-healing would and osteomyelitis. A four-month
      history of an enlarging mass within the ulcer suggested squamous cell carcinoma,
      which was confirmed by biopsies. The patient was treated with Mohs micrographic
      surgery for local eradication of the tumor, intravenous antibiotics, and skin
      grafting.

PMID- 9611605
TI  - Needs of the homebound morbidly obese patient: a descriptive survey of home
      health nurses.
AB  - The purpose of this descriptive survey was to identify challenges encountered by
      the home care provider when caring for a morbidly obese client in the home care
      setting and to provide recommendations to those involved in the transition of the
      patient from the acute care setting to the home. This descriptive study used a
      convenience sample of 25 RNs employed in one of the many referral home care
      agencies in the greater Los Angeles, California area. The referral home care
      agencies were selected randomly. Criterion for inclusion was that the nurse had
      cared for at least three patients in the past 12 months with a Body Mass Index
      (BMI) of > or = 40. A semi-structured interview was completed using a ten item
      survey tool which included open ended questions. One hundred percent of the
      subjects approached participated (N = 25). The home care setting was their
      primary place of employment for at least 2 years (mean 5 years), and each RN had
      cared for an average of 4 patients with a BMI of greater than 40 in the past
      years. Challenges expressed by the nurses in the home care setting include:
      equipment (n = 25), reimbursement (n = 25), access to resources (n = 18), client
      motivation (n = 8), and family/significant other support (n = 10).

PMID- 9611606
TI  - Alternative medicine and wound healing.
AB  - Alternative and complementary medicine includes a vast array of both modalities
      for which the client is a passive recipient ant and self-care techniques. As a
      result of individuals taking more charge of their health as well as becoming
      disenchanted with the costs and outcomes of allopathic care, interest in this
      area is rapidly growing. Some alternative and complementary may offer benefits
      for patients with wounds and wound pain. These therapies include acupuncture,
      energy healing, guided imagery, hypnosis, prayer, and relaxation techniques. For
      each therapy identified here, a brief description as well as a summary of
      research in general and for wounds in particular is provided. In addition, the
      author's experience with implementing these therapies to complement state-of-the
      art wound care practices in an outpatient wound clinic is discussed.

PMID- 9611607
TI  - Diabetic ulcers of the lower extremity: a review of comprehensive management.
AB  - The management of lower extremity diabetic ulceration exacts enormous emotional
      and economic costs from patients, their family members and caregivers, and
      society. A team approach to wound healing has proved effective, but efforts at
      prevention have been less successful. The etiology of lower extremity diabetic
      ulcers includes injury complicated by underlying neuropathy, ischemia, or both.
      Prevention of primary and recurrent ulcers can be increased through programs to
      educate patients and caregivers. Proper management begins with thorough
      assessment and continues with various forms of medical and surgical therapy, and
      timely referral to specialists when appropriate. The use of recombinant growth
      factors is becoming more widespread as more is learned about their essential role
      in wound healing. Monitoring the wound while it is being treated is as important
      as initial assessment. Across the United States and Canada, wound care clinics
      are being established to provide intensive care directed by specially trained
      multidisciplinary care teams. Less populated areas must rely on proper education
      of ET nurses, home care nurses, visiting nurses, podiatrists/chiropodists, and
      allied healthcare professionals. Challenges for the future include the
      development of protocols for comprehensive assessment and care, better methods of
      prevention, a greater understanding of the role of growth factors in wound
      healing, and optimizing wound care.

PMID- 9611608
TI  - Mentoring: the ultimate professional relationship.
AB  - Mentoring plays a significant role in business, industry, government, education,
      and healthcare. Mentoring relationships help promote the individual's
      professional growth and development. Such development involves knowledge and
      skill acquisition, which is facilitated by interaction with other, more
      experienced and proficient professionals. The Belcher-Sibbald Continuum of
      Learning describes the relationship among the concepts of role modeling,
      networking, preceptoring, and mentoring. Each concept is defined and described as
      a unique relationship which promotes professional growth and development. In
      addition, three mentoring/networking relationships in the context of the wound
      care community are presented to provide insight into this type of relationship.

PMID- 9611609
TI  - Musings on sixty years in public health.
AB  - These reflections on six decades in public health work come from both personal
      experiences and observations in the field. Attention is given to changes in
      health problems during the period and how public health workers have responded to
      them. The commentary also touches on how one proceeds in public health, includes
      suggestions for effectiveness, notes some difficulties encountered, and briefly
      describes health progress. The evolution of public health to encompass a much
      broader scope of activity than in the 1930s and how that has come about is
      emphasized.

PMID- 9611610
TI  - Econometrics in outcomes research: the use of instrumental variables.
AB  - We describe an econometric technique, instrumental variables, that can be useful
      in estimating the effectiveness of clinical treatments in situations when a
      controlled trial has not or cannot be done. This technique relies upon the
      existence of one or more variables that induce substantial variation in the
      treatment variable but have no direct effect on the outcome variable of interest.
      We illustrate the use of the technique with an application to aggressive
      treatment of acute myocardial infarction in the elderly.

PMID- 9611611
TI  - Assessment of occupational exposures in community-based case-control studies.
AB  - Assessing occupational exposures in community-based studies is a challenge for
      investigators because there are no standardized or validated approaches for
      collecting information regarding occupational history. The strengths and
      limitations of the methods available for assessing occupational exposures are
      reviewed. In community-based case-control studies, the prevalence of most
      chemical agents is low. The common sources of misclassification in these studies
      are addressed, as are strategies for dealing with misclassification bias. Methods
      to assess the presence and magnitude of differential reporting by cases and
      controls are outlined, together with analytic strategies to improve the
      classification of occupational exposures.

PMID- 9611612
TI  - Hormone replacement therapy, heart disease, and other considerations.
AB  - Multiple observational studies suggest a marked reduction in risk of coronary
      heart disease (CHD) associated with postmenopausal estrogen use. A new meta
      analysis presented here extends these results to estrogen plus progestin
      regimens. Although the findings from observational studies are strong and
      consistent, and there are several plausible mechanisms by which estrogen might
      reduce risk for CHD, most of the known biases would tend to exaggerate estrogen's
      benefit. Further, estrogen therapy clearly increases risk for endometrial
      hyperplasia and cancer, venous thromboembolic events and gallbladder disease, and
      long-term use probably also increases the risk of breast cancer. Therefore, until
      findings from randomized trials confirm and quantitate the benefit of estrogen
      therapy for prevention of CHD, we believe it should not be recommended to all
      postmenopausal women.

PMID- 9611613
TI  - Chemoprevention of lung cancer: the rise and demise of beta-carotene.
AB  - Beta-carotene and retinoids were the most promising agents against common cancers
      when the National Cancer Institute mounted a substantial program of population
      based trials in the early 1980s. Both major lung cancer chemoprevention trials
      not only showed no benefit, but had significant increases in lung cancer
      incidence and in cardiovascular and total mortality. A new generation of
      laboratory research has been stimulated. Rational public health recommendations
      at this time include: 1. Five-A-Day servings of fruits and vegetables, a doubling
      of current mean intake; 2. systematic investigation of the covariates of extremes
      of fruit and vegetable intake; 3. discouragement of beta-carotene supplement use,
      due to adverse effects in smokers and no evidence of benefit in non-smokers; 4.
      multilevel research to develop and evaluate candidate chemoprevention agents to
      prevent lung and other common cancers; and 5. continued priority for smoking
      prevention, smoking cessation, and avoidance of known carcinogens in the
      environment.

PMID- 9611614
TI  - Environmental risk factors and female breast cancer.
AB  - The increasing incidence of breast cancer in the United States and the
      international variation in risk have led to speculation that environmental risk
      factors are an important cause of breast cancer. We review the epidemiologic
      evidence on the breast cancer risk associated with ambient environmental
      exposures experienced passively by the US population, and discuss the
      difficulties associated with measurement of specific exposures in environmental
      studies. We review geographic variation of breast cancer rates in the United
      States, and exposure to organochlorines, ionizing and electromagnetic radiation,
      and passive smoking. Results are inconclusive but do not support a major role of
      environmental risk factors in the etiology of breast cancer.

PMID- 9611615
TI  - Evaluating the cost-effectiveness of clinical and public health measures.
AB  - Cost-effectiveness analysis, an analytic tool that expresses as a ratio the cost
      of obtaining an additional unit of health outcome, can help decision makers
      achieve more health protection for the same or less cost. We characterize the
      state of the cost-effectiveness analysis literature by reviewing how this
      technique is applied to various clinical and public health interventions. We
      describe the results of cost-effectiveness analyses for over 40 interventions to
      reduce cancer, heart disease, trauma, and infectious disease. The cost
      effectiveness ratios for these interventions vary enormously, from interventions
      that save money to those that cost more than $1 million per year of life gained.
      The methods used to derive the cost-effectiveness ratios also vary considerably,
      and we summarize this variation within each health area. Greater uniformity of
      analytical practice will be necessary if cost-effectiveness analysis is to become
      a more influential tool in debates about resource allocation.

PMID- 9611616
TI  - Public health in central and eastern Europe and the role of environmental
      pollution.
AB  - The central and eastern European countries that composed the former Eastern Bloc
      have experienced an alarming decline in public health since the dissolution of
      the Soviet Union. Death rates have increased in most age groups. Life expectancy,
      especially among males, has decreased in many countries; in Russia, male life
      expectancy dropped by six years between 1989 and 1994. By 2020, these countries
      are projected to have smaller increases in life expectancy than any other
      geographic region. The conditions responsible for the excess mortality are
      cardiovascular disease, cancer, and injuries among adults. The major factors in
      the sharp increase are poverty, social disintegration, and crime, overlaid on
      historically high rates of smoking, alcohol use, and psychosocial stress.
      Environmental pollution, although common and sometimes severe in the former
      Eastern Bloc, is another, albeit not the chief, cause of the sharp decline in
      public health since 1989.

PMID- 9611617
TI  - Review of community-based research: assessing partnership approaches to improve
      public health.
AB  - Community-based research in public health focuses on social, structural, and
      physical environmental inequities through active involvement of community
      members, organizational representatives, and researchers in all aspects of the
      research process. Partners contribute their expertise to enhance understanding of
      a given phenomenon and to integrate the knowledge gained with action to benefit
      the community involved. This review provides a synthesis of key principles of
      community-based research, examines its place within the context of different
      scientific paradigms, discusses rationales for its use, and explores major
      challenges and facilitating factors and their implications for conducting
      effective community-based research aimed at improving the public's health.

PMID- 9611618
TI  - Youth access to tobacco: policies and politics.
AB  - The late 1980s marked the beginning of a sea change in research and intervention
      on tobacco use by young people, when the first studies were published
      demonstrating the ease with which adolescents could purchase cigarettes. Since
      then concern with the commercial availability of tobacco products to youth has
      grown, becoming deeply entrenched in both research and policy efforts. This paper
      reviews the history of restrictions on youth access to tobacco, the evidence that
      commercial sources of tobacco are available and important to adolescents, and the
      rationale for various components of policies to restrict access. We also review
      the recent expansion of policies addressing youth access to tobacco at all levels
      of government, the tobacco industry response to this expansion, and issues that
      have arisen as this expansion has developed.

PMID- 9611619
TI  - Tick-transmitted infectious diseases in the United States.
AB  - The epidemiologic concept of tick-transmitted diseases has increased in
      importance with the recognition of the emerging infectious diseases, Lyme
      borreliosis, human monocytotropic and granulocytotropic ehrlichioses, and three
      different babesioses. Effective public health control of these diseases would
      depend upon critical knowledge of the vector biology of the ticks that transmit
      them. Rocky Mountain spotted fever and the human ehrlichioses are life
      threatening yet treatable diseases. A major problem remains establishment of the
      diagnosis when treatment decisions are being made. Clinical manifestations, other
      than erythema migrans for Lyme borreliosis, do not provide strong diagnostic
      clues. Ehrlichiae or babesiae are often not detected in peripheral blood smears.
      Frequently there are no antibodies to these diverse agents at the time of
      presentation, and isolation does not yield sensitive and timely results.
      Polymerase chain reaction, still a research tool, promises the greatest
      sensitivity, specificity, and timeliness. Prevention by vaccines is not yet a
      reality, although OspA-based vaccines offer hope for the prevention of Lyme
      disease.

PMID- 9611620
TI  - Preventing youth violence: what works?
AB  - Between 1985 and 1992, serious youth violence in the United States surged to
      unprecedented levels. The growing use of firearms to settle disputes has
      contributed to this phenomenon. Youth are most often victimized by one of their
      peers. In response to this problem, a wide variety of programs have been
      implemented in an attempt to prevent youth violence or reduce its severity. Few
      have been adequately evaluated. In general, interventions applied between the
      prenatal period and age 6 appear to be more effective than interventions
      initiated in later childhood or adolescence. Community-based programs that target
      certain high-risk behaviors may be beneficial as well. A sustained commitment to
      evaluation research is needed to identify the most effective approaches to youth
      violence prevention.

PMID- 9611621
TI  - Prevention of bicycle-related injuries: helmets, education, and legislation.
AB  - Efforts to reduce the toll of bicycle-related head injuries illustrate how the
      basic public health principles of surveillance, epidemiologic study,
      intervention, and evaluation can have a substantial impact on an injury problem,
      using a variety of injury-prevention strategies. Head injuries are the leading
      cause of serious morbidity and mortality from bicycle crashes. Helmets have been
      shown to reduce bicycle-related head injuries for cyclists of all ages involved
      in all types of crashes including those with motor vehicles. Helmet use has been
      promoted using educational campaigns, helmet subsidies, and legislation. Careful
      evaluation of these strategies has shown that these interventions increase helmet
      use and decrease the incidence of bicycle injuries. The model developed for the
      prevention of bicycle injuries is widely applicable to other injury problems.

PMID- 9611622
TI  - Successful behavioral interventions to prevent cancer: the example of skin
      cancer.
AB  - Important behavioral sources of risk for cancer have been identified and programs
      to reduce this risk have been initiated. The most heavily studied behavioral risk
      is tobacco use, but considerable attention has also gone to prevention of skin
      cancer by modifying sun exposure. Research has shown a strong link between sun
      exposure and skin cancer, and opportunities to prevent this cancer by changing
      behavior should be effective. Unlike unmodifiable sources of risk, sun exposure
      should be modifiable through behavioral intervention. This review considers
      research in this expanding area, concentrating on predictors of sun protective
      behaviors, modification of sun exposure, and surveillance for early signs of
      cancer. The elements of behavior change programs that contribute to successful
      intervention as well as barriers to successful behavior change and future
      directions for this effort are considered.

PMID- 9611623
TI  - Tobacco dependence treatments: review and prospectus.
AB  - Cigarette smoking continues to place an enormous burden on US health systems. The
      treatment of tobacco-dependent persons is vital to the public health, since
      unmitigated smoking could lead to the development of disease and premature death
      in as many as 20 million current smokers in the United States. Much of this
      tobacco-related morbidity and mortality could be prevented by the application of
      existing treatments, as well as newer ones. Access to safe and effective
      treatments was significantly expanded in 1996, when two forms of nicotine
      replacement therapy (NRT), the nicotine gum and patch, became available for over
      the-counter sale. Expanded access has led to significantly increased utilization
      and quitting. Even with these advances, however, the scope of this tobacco
      dependence demands that we explore alternative treatment strategies, including
      exposure reduction therapy (ERT) as a possible option for smokers not currently
      making quit attempts. In this review, we present principles to guide the
      development of such a therapy, and for its application, should it be proven
      effective.

PMID- 9611624
TI  - Strategies to reduce driving under the influence of alcohol.
AB  - The purpose of this review is to update research on the prevention of alcohol
      related traffic deaths since the 1988 Surgeon General's Workshop on Drunk
      Driving. Four primary areas of research are reviewed here: (a) general deterrence
      policies, (b) alcohol control policies, (c) mass communications campaigns,
      including advertising restrictions, and (d) community traffic safety programs.
      Modern efforts to combat drunk driving in the United States began with specific
      deterrence strategies to punish convicted drunk drivers, and then evolved to
      include general deterrence strategies that were targeted to the population as a
      whole. Efforts next expanded to include the alcohol side of the problem, with
      measures installed to decrease underage drinking and excessive alcohol
      consumption. In the next several years, greater efforts are needed on all these
      fronts. Also needed, however, are programs that integrate drunk driving
      prevention with other traffic safety initiatives.

PMID- 9611625
TI  - Implications of the results of community intervention trials.
AB  - This paper examines the results of population-level interventions conducted in
      three settings: entire communities, worksites, and schools. Four major
      conclusions are discussed: (a) Directions for the next generation of community
      based interventions include targeting multiple levels of influence; addressing
      social inequalities in disease risk; involving communities in program planning
      and implementation; incorporating approaches for "tailoring" interventions; and
      utilizing rigorous process evaluation. (b) In addition to randomized controlled
      trials, it is time to use the full range of research phases available, from
      hypothesis generation and methods development to dissemination research. (c) The
      public health research agenda may have contributed to observed secular trends by
      placing behavioral risk factors on the social and media agendas. (d) The
      magnitude of the results of community intervention trials must be judged
      according to their potential public health or population-level effects. Small
      changes at the individual level may result in large benefits at the population
      level.

PMID- 9611626
TI  - Organizational diversification in the American hospital.
AB  - This paper outlines a conceptual framework of organizational diversification and
      assesses the state of empirical research on hospital organizational change. The
      literature on economic organization of hospitals, one of the most developed
      branches of health services research, still has only weak ties to economic
      theory. Evolving physician-hospital organizations do not fit into existing
      frameworks based on horizontal integration, vertical integration, or
      diversification. Empirical research has primarily focused on horizontal
      integration, and cause-effect relationships are often obscured by models that
      depart from economic theory and lack controls for self-selection bias. Recent
      empirical studies indicate that hospital mergers had moderate, rather than
      dramatic, effects on the rate of change in operating costs, staffing, and scale.
      Mergers rarely resulted in hospital closure, but were as likely to result in
      acute care consolidation and restructuring as in conversion to non-acute
      inpatient uses. While administrative costs were higher in for-profit than non
      profit system hospitals, total costs were similar. System hospitals had lower
      marginal and average costs per stay than independent hospitals. Hospital vertical
      integration into subacute care was largely an artifact of the governmental
      uniform pricing system, which encouraged vertical integration. Hospitals that
      shared governance or financial risks with physicians outperformed those with high
      levels of physician governance and financial integration (e.g. stock ownership).
      Formal physician-hospital organizational arrangements often served to coordinate
      managed care contracting or to forge links with primary care group practices.
      Hospital diversification into related services improved short-term financial
      performance over unrelated diversification, although long-term performance was
      similar.

PMID- 9611627
TI  - A mini-symposium on managed care: introduction.

PMID- 9611628
TI  - Medicare and managed care.
AB  - Medicare offers nearly universal, but limited, coverage for the elderly. The vast
      majority of beneficiaries therefore obtain supplemental coverage, or they enroll
      in HMOs to gain extra benefits at substantially lower or zero cost. This is
      possible because of reduced utilization and costs, as well as favorable selection
      of lower-risk enrollees into HMOs. Competition from HMOs may lower local fee-for
      service costs as well. Quality and satisfaction measures are quite balanced, with
      some results showing better HMO performance and some worse. The absence of
      adequate risk-adjusted payments to HMOs, however, gives them little incentive to
      develop high-quality programs for the sickest enrollees.

PMID- 9611629
TI  - Managed care data and public health: the experience of Group Health Cooperative
      of Puget Sound.
AB  - Traditional group and staff model HMOs have contributed to public health
      investigations for decades. HMOs offer several advantages for this type of
      research because of their defined population and provider groups and the
      integrated nature of care delivery in these organizations. Traditional HMOs have
      also made investments in sophisticated data systems to support evidence-based
      care that is supported by high-quality clinical data available in automated
      information systems. This paper reviews why traditional HMOs are ideal places to
      conduct public health research and analyzes how recent market trends may threaten
      this role for managed care.

PMID- 9611630
TI  - Mental health and managed care.
AB  - Managed care has become the dominant method for financing and delivering care for
      common mental health problems and for people with severe, chronic mental health
      conditions. Despite the rapid growth of managed mental health care, there is very
      little research available to guide policy choices. Managed care has led to
      decreased costs for employers and other payers, mostly through reducing hospital
      admissions or length of stay. Managed care organizations use staff with lesser
      levels of training (e.g. social workers instead of psychiatrists) and are more
      likely to offer group outpatient programs and manualized treatment than their fee
      for-service counterparts. Despite these differences, there is no clear evidence
      that health outcomes are worse for patients in managed care. There is an urgent
      need for researchers to turn their attention to issues such as cost, quality,
      access, satisfaction, and functional outcomes associated with managed mental
      health care. The impact of parity of mental health with insurance coverage for
      physical conditions is another important question that needs to be addressed.

PMID- 9611631
TI  - Early and periodic screening, diagnosis, and treatment and managed care.
AB  - This paper presents evidence on the performance of Medicaid managed care
      organizations (MCOs) in providing Early and Periodic Screening, Diagnosis, and
      Treatment (EPSDT) services to children under age 21. States face considerable
      challenges in integrating EPSDT into managed care. For example, MCOs rarely offer
      all services required under federal law. Also, MCOs often are unable to meet
      state reporting requirements. On the other hand, MCOs offer children a medical
      home, often for the first time, that may encourage timely preventive care. The
      literature generally shows no differences in the performance of MCOs relative to
      traditional FFS providers in the EPSDT participation rate. Future needs include
      improving the specificity of contract language, more precisely defining the EPSDT
      benefit package, evaluating the adequacy of EPSDT payments, monitoring the
      capacity of MCO provider networks, establishing the effectiveness of outreach and
      enabling services, developing standardized MCO reporting requirements,
      documenting program outcomes, and assessing benchmarks for accountability.

PMID- 9611632
TI  - Managed care and public health departments: who is responsible for the health of
      the population?
AB  - This review examines changes over the past decade in the delivery of health care
      in the United States, specifically the move toward managed care and capitation.
      Over 77 million Americans are now enrolled in health maintenance organizations,
      and the health care delivery system is reorganizing into large group practices
      and integrated health systems. Examined here are the implications of this shift
      on the interaction between managed care and public health agencies. How will a
      population-based system of health care be achieved in light of managed care
      organizations' responsibility only for their enrolled population, in contrast to
      the responsibility of the public health service for the entire population? Where
      does the responsibility of MCOs end and that of public health begin? Should
      certain public health functions be absorbed by managed care organizations? What
      are the prospects for partnership between these two systems?

PMID- 9611633
TI  - [Should we administer replacement therapy to patients with alpha-1-antitrypsin
      deficit?].

PMID- 9611634
TI  - [Surgery of lung metastasis: results of a hospital survey in the Autonomous
      Community of Madrid. Working Group on Surgery of Lung Metastasis (GT-CMP)].
AB  - The Task Force on Pulmonary Metastasis Surgery of the Oncology Department of the
      Madrid Pneumology and Chest Surgery Society designed a questionnaire to determine
      guidelines for surgery to resect lung metastases in the Autonomous Community of
      Madrid, an area with over four million inhabitants. The questionnaire was divided
      into five sections: indications, diagnostic procedures, extension studies,
      disciplinary foci and surgical techniques. Ten of the hospitals surveyed answered
      the questionnaire. We found that disagreement is high regarding patient
      screening, and that there are differences regarding some preoperative procedures
      and extension studies, as well as in therapeutic approach. Eighty percent of the
      respondents were not in favor of using video assisted thoracoscopy as a
      therapeutic technique, and disagreement was greater regarding approaches
      technique, and disagreement was greater, regarding approaches to bilateral
      metastases. We infer that between 100 and 120 cases are treated surgically every
      year. Procedures to join The International Lung Metastases Registry have started.

PMID- 9611635
TI  - [Descriptive study of complications caused by mediastinoscopy].
AB  - To analyze the surgical and non surgical complications of mediastinoscopy in a
      series of 200 consecutive patients. Retrospective study of all surgical patients
      between 1 January 1994 and 1 May 1997. Any complication presenting between time
      of surgery and patient release is analyzed. Complications were seen in 8 out of
      200 cases (4%). In three cases, there were lesions in neighboring structures
      (recurrent nerve, bronchial artery and innominate artery). The rest were non
      surgical complications (3 cases of arrhythmia, 2 of prolonged mechanical
      ventilation). One male patient (0.5%) died from cerebral infarction, probably as
      a result of arterial occlusion needed to suture damage to the innominate artery.
      Superior win cava syndrome affected 20% (1 in 5) and morbidity was 60% (3 in 5).
      Morbidity involving both medical and surgical complications in this series is
      higher than that reported elsewhere in the literature, in series for which non
      surgical complications go unreported.

PMID- 9611636
TI  - [Delays in the diagnosis and surgical treatment of bronchogenic carcinoma.
      Cooperative Group on Bronchogenic Carcinoma of SEPAR (GCCB-S)].
AB  - The aim of this study was to determine the delay between clinical suspicion and
      diagnosis of bronchogenic carcinoma, and between diagnosis and performance of
      therapeutic thoracotomy. The study population included 598 patients undergoing
      surgery between October 1995 and September 1996 registered in the Bronchogenic
      Carcinoma Cooperation Group of SEPAR (BCCG-S), and 49 patients from our hospital
      undergoing surgery during the same period. The mean delay between diagnosis and
      thoracotomy was 45.15 days (SD 34.7 days) for BCCG-S patients and 53.5 days (SD
      22 days) for our hospital patients. In the second group, mean time elapsing
      between diagnosis suspicion and performance of bronchoscopy was known to be 9.5
      days (SD 14.7 days), with the lowest periods recorded for inpatients (3.1 +/- 1.7
      days) and for patients who did not require chest x ray guided bronchoscopy (5 +/-
      5.8 days). These data are similar to those published for hospitals in other
      countries. They must be considered long delays and should be shortened.

PMID- 9611637
TI  - [Role of postoperative estimate of maximum oxygen uptake in predicting
      cardiorespiratory insufficiency in the immediate postoperative period in thoracic
      surgery].
AB  - We sought to determine if predicted post-operative maximal oxygen uptake
      (VO2max/kg-PPO) was associated to the occurrence of respiratory or cardiac
      failure within the 60 days following lung surgery and to evaluate its validity as
      operability criterion. We studied 47 patients with chronic air-flow limitation
      (COPD) with FEV1 > 0.8 1 and without hypercapnia, that underwent lung surgery.
      Age was 56 (SD 11) years, FEV1 = 1.8 (SD 0.5) 1 (61% predicted (SD 13%) and
      FEV1/FVC = 55 (SD 7.5). Ten patients presented serious cardiac or respiratory
      complications (3 died). Significant correlation with complications was found for
      RV, TL-COsb-PPO, VO2max/kg, resection size and VO2max/kg-PPO. VO2max/kg-PPO
      correlation (-0.73) was significantly higher (p = 0.0016) than all the pulmonary
      function test (PFT) correlation and than VO2max/kg correlation (p = 0.049) as
      well. Cut-off points, positive and negative predictive values were respectively:
      12.6 ml/min/kg, 0.75 y 0.90% for VO2max/kg-PPO; 17 ml/min/kg 0.83 and 0.87 for
      VO2max/kg and 148%, 0.67 and 0.82 for RV (the best of the pulmonary function
      tests). Multivariable models did not improve discriminant power. We conclude
      that, out of the studied variables, VO2max/kg-PPO showed higher correlation with
      the complications sought than PFT or VO2max/kg. As criterion to predict cardiac
      or respiratory failure, with the observed prevalence, its negative predictive
      values is good, but its positive predictive value is relatively low. None
      parameter was able to predict all the complications.

PMID- 9611638
TI  - [Factors related to diagnostic yield and complications of transbronchial biopsy].
AB  - To study the diagnostic yield of transbronchial biopsy (TBB) in lung diseases of
      different ethiology, as well as to examine several factors implicated in
      diagnostic yield and complications of TBB. Retrospective study of a series of 172
      patients (98 women and 74 men) undergoing TBB. Clinical variables, x-ray and CT
      patterns and technical factors related to TBB were analyzed in relation to
      diagnostic yield and definitive diagnosis. We recorded the main complications and
      studied the possible mechanisms implicated in their appearance. The results of
      TBB were classified as follows: 1) diagnostic TBB (42.8%); 2) nonspecific TBB
      (21.1%); absence of parenchyma (NP) (9.7%); 4) normal parenchyma (23.4%); 5)
      incorrect diagnosis (2.9%). Overall yield was 43.6% but rose to 52% when NP and
      no infiltrative pneumopathies were excluded. The main findings were infections
      (23.4%), neoplasms (19.4%), sarcoidosis (14.2%), idiopathic pulmonary fibrosis
      (IPF) (17.7%); and other (23.4%). Significant differences in diagnosis were found
      for age, sex, time of evolution prior to TBB, and x-ray and CT patterns.
      Complications and pneumothorax appeared more frequently in IPF, neoplasms and
      infections, although the differences were non significant. Diagnostic value
      depended mainly on type of disease and ranged from 60% for sarcoidosis to 24% for
      IPF (p < 0.05), with no differences related to age, sex, presence of
      immunosuppression, number of TBB or tolerance to exploration. Yield was higher,
      however, for patients with no loss of radiographic pulmonary volume (56.3% versus
      37.5%) and with absence of a CT reticular pattern (44.7% versus 27.3%). Type of
      opacites also influenced yield (53.4% for ground glass versus 26.7% for reticular
      patterns), as did distribution of lesions (8.4% for peripheral patterns versus
      48.3% for diffuse patterns and 50% for peribronchio-vascular patterns). The site
      of TBB was the only factor showing clearly significant differences in yield (100%
      in mild lobe versus 29.5% in upper lobes). Tolerance was poorer in older patients
      (63.5 +/- 10 versus 52.2 +/- 17 years) and with greater function abnormalities
      (%FEV1: 48.2 +/- 16.8 versus 70.2 +/- 17.1). Poor tolerance of exploration was
      associated with the appearance of complications (16.6% vs 6.3) and pneumothorax
      (25% versus 6.8%). The diagnostic yield of TBB was mainly influenced by the type
      of disease studied. The various imaging techniques were fundamental for
      establishing preliminary diagnoses and degree of evolution of a specific cases.
      In our series, tolerance of the technique was a reliable predictor of
      complications and the presence of post-biops pneumothorax.

PMID- 9611639
TI  - [Normative of arterial gas analysis. Working Group of the SEPAR for the practice
      of arterial gas analysis].

PMID- 9611640
TI  - [Nomenclature and classification of mycobacteria].

PMID- 9611641
TI  - [Steroid treatment: risk factor for invasive pulmonary aspergillosis].
AB  - To describe the association between invasive pulmonary aspergillosis and steroid
      treatment in patients with no immunodepression attributable to other causes. We
      reviewed the case histories of apparently non immunodepressed patients in our
      hospital with histological diagnoses of invasive pulmonary aspergillosis between
      1992 through 1996. Seven patients were identified. Laboratory, clinical and
      radiological data were collected, as well as type and duration of steroid
      treatment. Four patients suffered underlying chronic obstructive pulmonary
      disease, 1 had temporal arteritis, 1 interstitial pulmonary fibrosis and 1 a
      neurological tumor. All had received steroid treatment for periods varying from
      several days to 16 months, at varying doses, although the majority of them were
      treated with 1mg/kg/day. All presented clinical profiles suggestive of pneumonia
      (5 community acquired and 2 nosocomial). Invasive pulmonary aspergillosis can
      appear in minimally immunocompromised patients, such as those undergoing steroid
      treatment and must be suspected whenever pneumonia is seen in patients receiving
      steroids who do not improve with widespectrum antibiotic treatment.

PMID- 9611642
TI  - [Non-invasive assessment of a snorer with diurnal hypersomnia without features of
      sleep apnea].
AB  - We report a case of increased upper airway resistance diagnosed by impedance
      plethysmograph. This simple non invasive technique may provide an alternative to
      polysomnography administered with an esophageal tube, particularly to screen
      patients before ordering further studies.

PMID- 9611643
TI  - [Cytohistologic consistency of transthoracic puncture-aspiration with fine needle
      in malignant lesions].

PMID- 9611644
TI  - [Tracheal rupture caused by strangulation].

PMID- 9611645
TI  - [Disabling chronic respiratory disease and alcoholism].

PMID- 9611646
TI  - [Sarcoma induced by radiotherapy in the treatment of breast carcinoma].

PMID- 9611647
TI  - [Lymphomatoid granulomatosis with atypical presentation].

PMID- 9611648
TI  - [Pulmonary aspergilloma and broncholithiasis].

PMID- 9611649
TI  - [Obstructive sleep apnea syndrome. Controversies concerning treatment].

PMID- 9611650
TI  - [Current situation of neoadjuvant chemotherapy in non-small-cell bronchogenic
      carcinoma].

PMID- 9611651
TI  - [Obstructive sleep apnea syndrome in the Community of Valencia: current
      situation, study of needs and future prospects].
AB  - To analyze the infrastructure needs for diagnosing sleep apnea syndrome (SAS) in
      the Community of Valencia, we studied available resources and the diagnostic
      approaches to SAS in departments of pneumology and neurophysiology in 23 of the
      25 public hospitals by means of a telephone interview. Only 52% of pneumology
      departments and 56% of neurophysiology departments studied SAS at any level.
      Level I study (conventional polysomnography) was performed by 42% of the
      pneumology departments and 100% of the neurophysiology departments. The remaining
      pneumology units used nighttime oximetry (a level IV technique). A special unit
      and trained personnel were available at 40% of hospitals. Home studies were
      performed by only 17%. Although 2,000 studies are performed annually, only 1,100
      are level I and large interdepartmental differences were detected. The average
      waiting period was 16 months. Relations between pneumology and neurophysiology
      units were few and only one hospital took an interdisciplinary approach. The
      ratio of polysomnographs to inhabitants was 0.52/250,000 and the prevalence of
      nasal continuous positive airway pressure treatment was 36/100,000, lower than in
      other communities. We conclude that Valencia is understaffed and under-equipped,
      and that in some cases resources are under-used. Interdisciplinary approaches are
      scarcely used by the various specialists involved and the waiting lists for
      diagnostic tests required for prescribing empirical treatment are long. To attend
      the approximately 100,000 SAS patients estimated to reside in Valencia, it would
      be necessary to have 14 polysomnograph devices rather than the 8 available now,
      as well as to increase staff to meet demand and shorten waiting lists.

PMID- 9611653
TI  - [Fiber morphometry of the external intercostal muscle. Comparison of dominant and
      nondominant sides in patients with severe COPD].
AB  - The general morphometric characteristics of the external intercostal muscle (EIM)
      of patients with chronic respiratory disease have been well described. Because
      this muscle is highly accessible, it can provide an ideal model for longitudinal
      studies using consecutive biopsies of both sides. Whether or not the EIM fiber
      phenotype is homogeneous on dominant (D) and non dominant (ND) sides is unknown,
      however. To evaluate possible structural differences in right and left EIM in
      patients with COPD, eight patients (63 +/- 7 years of age) were enrolled. Lung
      function, respiratory muscle power, general muscle power and nutritional state
      were evaluated. Biopsies of the fifth EIM were taken from both sides. Specimens
      were processed in parallel manner to determine conventional morphometry
      (hematoxylin-eosin staining), including minimum diameter (Dm) and fiber area (Ar)
      in cross sections. Fibers were typed by ATPase (at pH 4.2, 4.6 and 9.4) and NADH
      TR staining. Nutrition was normal in all patients. All patients had severe COPD
      (FEV1 27 +/- 7% of reference, limits 13 to 38% of reference) with air entrapment
      (RV 163 +/- 36% of reference, limits 181 to 276% of reference). None of the
      patients showed respiratory insufficiency at rest (PaO2 72 +/- 7 mmHg).
      Peripheral musculoskeletal power measured by manual dynamometer showed no
      significant right-left differences: D 29 +/- 2 and ND 28 +/- 3 dynes.
      Morphometric study of 16 muscle specimens showed no significant differences
      between fiber size on D and ND sides. DmD was 47 +/- 10 microns and ArD, was
      2,595 +/- 1,249 microns2. DmD was 49 +/- 9 microns and ArD was 2,636 +/- 953
      microns2. Likewise, no significant differences were found between D and ND fiber
      types: type ID 51 +/- 4% and type IID 49 +/- 5% versus type IND 52 +/- 4% and
      type IIND 48 +/- 4%. EIM on N and ND sides is homogeneous at the fifth
      intercostal space. This finding, along with the scarcely invasive nature of the
      technique for collecting specimens leads us to suggest that longitudinal studies
      might be performed on the structural effects of various pharmacological or
      physical treatments followed by COPD patients

PMID- 9611652
TI  - [Spontaneous pneumothorax associated with human immunodeficiency virus (HIV)
      infection].
AB  - Spontaneous pneumothorax is a relatively frequent complication of human
      immunodeficiency virus (HIV) infection. Seven hundred sixty-five HIV-infected
      inpatients were treated at Marques de Valdecilla University Hospital between 1990
      and 1996. Spontaneous pneumothorax developed in 9 patients. Pneumocystis carinii
      pneumonia was diagnosed in 6 patients (66%), either before or simultaneous to the
      appearance of pneumothorax. Pneumothorax was related to active or old
      tuberculosis infection in 3 patients (33%). Prophylactic therapy with nebulized
      pentamidine was used in 55% of the patients. Successful initial control of
      pneumothorax was achieved with simple drains in 58% of the episodes, although the
      recurrence rate was 71%. Pleurodesis with talcum with a chest tube was used
      successfully in 3 patients, in 2 because of sings of persistent air leakage
      uncorrected by simple drainage. Pleurodesis initially failed but later controlled
      pneumothorax the second time it was used. The mortality rate in this series was
      66%, with a mean survival time of 55.6 days. We conclude that spontaneous
      pneumothorax is associated with poor prognosis in HIV infected patients. Prior or
      concurrent P. carinni pneumonia or tuberculosis were the etiologic factors
      identified in our patients. A simple pleural drain was associated with a high
      rate of recurrence, such that pleurodesis seems warranted in all patients.

PMID- 9611654
TI  - [Role of endogenous nitric oxide (NO) in pulmonary vascular adaptation to one
      lung ventilation during thoracic surgery].
AB  - To determine whether endogenous production of nitric oxide (NO) increases during
      one-lung lung ventilation (OLV) and to observe its possible influence on
      pulmonary vascular resistance (PVR). The experimental group consisted of 19
      patients undergoing chest surgery with OLV, with monitoring by Swan-Ganz
      catheter. Hemodynamic parameters were measured and peripheral venous blood
      samples were taken at the start of surgery and 10 minutes after starting OLV. The
      control group consisted of 13 patients with comparable clinical characteristics
      undergoing chest surgery with conventional lung ventilation. In this group
      samples of peripheral venous blood were taken at the start of surgery and at a
      moment comparable to the sampling of the experimental group. NO was assessed by
      quantitative colorimetry as the concentration of nitrites in venous blood.
      Nitrite concentration in the experimental group was higher during OLV (12.7 +/-
      10.1 muMol/ml) than initially (7.1 +/- 5.4 muMol/ml) (p < 0.05). Nitrite
      concentration was similar at the two moments sampled in the control group (8.7 +/
      2.8 muMol/ml at the start of surgery and 8.1 +/- 3.2 muMol/ml in the second
      sample taken). Mean percent increase in nitrite concentration in the experimental
      group was 93.7 +/- 117%; mean percent change in the control group was 3.9 +/- 23%
      (p < 0.001). PVR during OLV (134 +/- 45 din.s.cm-5) is lower than at the start of
      surgery (163 +/- 37 din.s.cm-5, p < 0.05). During OLV endogenous production of
      NO, measured as nitrite concentration in plasma, increases. PVR decreases,
      possibly because of the increase in nitrite concentration.

PMID- 9611655
TI  - [Sex differences in experimentation and tobacco consumption by children,
      adolescents and young adults].
AB  - Studies carried out in the past ten years have found the prevalence or smoking
      among children and adolescents to be high, with the greatest increase observed
      for girls and young women, indicating increasing gender-related differences. The
      aim of our study was to determine the prevalences and differences among children
      and adolescents of both sexes with regard to experimentation and use of tobacco
      products and to determine any possible influence related to urban or rural
      environment. Eight hundred fourteen students participated, with 809 providing
      valid data for study: 385 males and 424 females ranging in age from 13 to 24
      years old (15.90 +/- 1.73 years). The subjects studied in either an urban or a
      rural school. Data was collected on campus by questionnaire and carbon monoxide
      in expired air was measured. Smoking had been tried by 68.2%: 241 males (62.5%)
      and 31 females (73.3%) (p < 0.001). Habitual smoking was reported by 27.2%: 78
      males (20.2%) and 142 females (33.4%) (p < 0.001). Mean ages of experimenters
      (16.18 +/- 1.78 years) and smokers (16.55 +/- 1.85 years) were higher than the
      mean age of non-experimenters (15.29 +/- 1.43) (p < 0.001). Habitual smokers
      consumed a mean 2.71 +/- 1.68 cigarettes/day and consumption was similar for both
      sexes. CO in expired air was 12.61 +/- 6.39 ppm in these smokers, significantly
      higher (p < 0.001) than that found in experimenters and non smokers (p 0.001).
      One hundred eighty students (22.2%), 119 females and 61 males (p < 0.001),
      reported having smoked on the morning of the study. In total, 81.8% of the
      students who described themselves as smokers had smoked that morning: 78.2% of
      the males and 83.9% of the females. CO in this group was 13.95 +/- 1.69 ppm,
      significantly higher than that found for the other groups (non smokers or
      experimenters). We found no significant differences between number of
      cigarettes/day smoked by students who reported being habitual smokers and the
      number consumed the morning of data collection by students who had smoked the day
      of the study. Changes can be observed in patterns of tobacco use among children
      and young people. We found that nearly all aspects related to experimentation and
      consumption of tobacco are significantly higher in females.

PMID- 9611656
TI  - [Treatment of sleep apnea-hypoapnea syndrome].

PMID- 9611657
TI  - [Consensus guidelines for respiratory endoscopy issued by the Argentine Society
      of Bronchoesophagology].
AB  - The international consensus is that guidelines for respiratory endoscopy are
      inadequate, regarding such issues as institutional requirements, benefits, risks
      and limitations of the procedure, training programs and accreditation, with the
      result that the way or performing endoscopy varies according to how an operator
      was trained. The absence of precise recommendations means that practice is highly
      diverse and inappropriate use of the procedure has increased. The Argentine
      Consensus Group for Normalization of Respiratory Endoscopy was created in 1995 to
      unify criteria for several aspects of endoscopic practice. The official
      recommendations of the Group and of the Argentine Society of Bronchoesophagology
      define the indications (diagnostic, therapeutic and investigative) and
      contraindications (absolute, relative and high risk) for bronchoscopy. Required
      pre-bronchoscopic studies for routine and special cases are defined, as are
      indications for premedication, intubation and general anesthesia. Requirements
      for the setting, support personal and instruments are specified. Guidelines for
      topical anesthesia and techniques for insertion of the endoscope are suggested.
      The technique, indications and limitations of bronchoalveolar lavage, bronchial
      brushing and biopsy and transbronchial needle biopsy are defined. The utility and
      limitations of the various therapeutic techniques of bronchoscopy (laser,
      radiotherapy and stents) are defined. Norms to safeguard the patient, instruments
      and operator are emphasized.

PMID- 9611658
TI  - [Granular cell myoblastoma localized in the thoracic wall].
AB  - We report the case or a 40-year-old man with a large right parasternal tumor.
      Computerized tomography (CT) and magnetic resonance (MR) imaging showed a soft
      tissue mass infiltrating contiguous structures with no sign of adenopathy and
      with disease limited the chest wall. The histological type was granular cell
      tumor (GCT) with discrete cell pleomorphism and nuclei that varied in form and
      size, with prominent nucleoli. Eighteen months after surgery, the patient was
      asymptomatic and disease free. GCT is a rare entity that is uncommonly found on
      the chest wall. A diagnosis of malignancy is established when metastasis is found
      to be of the same histological type as that of the primitive tumor. Neither cell
      pleomorphism or nuclei with nucleoli allows for a diagnosis of malignancy; only a
      size greater than 5 cm and locally invasive behavior should lead to an assumption
      that these tumors are of unspecified malignancy. We believe the treatment of
      choice for these lesions is radical removal

PMID- 9611659
TI  - [Isoniazid-food interactions].

PMID- 9611660
TI  - [Severe exacerbation of asthma caused by topical administration of ketoprofen].

PMID- 9611661
TI  - [Metastasis of giant cell anaplastic carcinoma of the lung to the small
      intestine].

PMID- 9611663
TI  - [Neurinoma of the vagus nerve].

PMID- 9611662
TI  - [Penile metastasis and pulmonary carcinoma].

PMID- 9611664
TI  - [Large pulmonary nodules as a presentation of sarcoidosis].

PMID- 9611665
TI  - [Hypoacusis and vertigo as a side effect of the use continuous positive airway
      pressure (nasal CPAP) in obstructive sleep apnea syndrome (OSAS)].

PMID- 9611666
TI  - Deja vu all over again.

PMID- 9611668
TI  - Global, regional, and local measures of complexity of multichannel
      electroencephalography in acute, neuroleptic-naive, first-break schizophrenics.
AB  - BACKGROUND: Schizophrenic symptoms commonly are felt to indicate a loosened
      coordination, i.e. a decreased connectivity of brain processes. METHODS: To
      address this hypothesis directly, global and regional multichannel
      electroencephalographic (EEG) complexities (omega complexity and dimensional
      complexity) and single channel EEG dimensional complexities were calculated from
      19-channel EEG data from 9 neuroleptic-naive, first-break, acute schizophrenics
      and 9 age- and sex-matched controls. Twenty artifact-free 2 second EEG epochs
      during resting with closed eyes were analyzed (2-30 Hz bandpass, average
      reference for global and regional complexities, local EEG gradient time series
      for single channels). RESULTS: Anterior regional Omega-Complexity was
      significantly increased in schizophrenics compared with controls (p < 0.001) and
      anterior regional Dimensional Complexity showed a trend for increase. Single
      channel Dimensional Complexity of local gradient waveshapes was prominently
      increased in the schizophrenics at the right precentral location (p = 0.003).
      CONCLUSIONS: The results indicate a loosened cooperativity or coordination (vice
      versa: an increased independence) of the active brain processes in the anterior
      brain regions of the schizophrenics.

PMID- 9611667
TI  - Ventricular enlargement in poor-outcome schizophrenia.
AB  - BACKGROUND: A subset of patients with schizophrenia, defined on the basis of
      longitudinal deficits in self-care, may show a classic ("Kraepelinian")
      degenerative course. An independent validator of the phenomenologically defined
      Kraepelinian subtype might be provided by a structural indicator of possible
      brain degeneration: ventricular size as measured by computed tomography (CT).
      METHODS: To examine whether Kraepelinian patients would show a differential
      increase in ventricular size over time, two CT scans were conducted at intervals
      separated by > 4 years, an average of 5 years. Fifty-three male patients with DSM
      III-R diagnoses of chronic schizophrenia were subdivided into Kraepelinian (n =
      22; mean age = 42 +/- 6 years) and non-Kraepelinian (n = 31; mean age = 38 +/-
      12.2 years) subgroups. Kraepelinian patients were defined on the basis of
      longitudinal criteria: > 5 years of complete dependence on others for life
      necessities and care, lack of employment, and sustained symptomatology. Thirteen
      normal elderly volunteers (mean age = 60 +/- 17.8) were also scanned at 4-year
      intervals. CT measurements were made by raters without knowledge of subgroup
      membership. A semiautomated computer program was used to trace the anterior horn,
      lateral ventricles, and temporal horns for each slice level on which they were
      clearly seen. RESULTS: The ventricles showed a bilateral increase in size over
      the 4-year interval in the Kraepelinian subgroup, more marked in the left
      hemisphere than the right. By contrast, neither the non-Kraepelinian subgroup nor
      the normal volunteers showed significant CT changes from scan 1 to scan 2.
      CONCLUSIONS: Thus, the longitudinal dysfunctions in self-care that characterize
      the Kraepelinian patients were associated with an independent indicator of brain
      abnormality.

PMID- 9611669
TI  - A double-blind, controlled comparison of the novel antipsychotic olanzapine
      versus haloperidol or placebo on anxious and depressive symptoms accompanying
      schizophrenia.
AB  - BACKGROUND: Depressive symptoms are a common feature of schizophrenia and may
      represent a core part of the illness. Where present, it has been associated with
      greater overall morbidity and mortality. Monotherapy with conventional dopamine
      antagonists may either worsen or bestow a limited therapeutic benefit.
      Accordingly the use of adjunctive thymoleptics has been explored. In contrast,
      olanzapine (OLZ), an atypical antipsychotic agent, offers a distinctive and
      pleotropic pharmacology suggestive of a broader efficacy profile than
      conventional neuroleptic agents. METHODS: In a 6-week placebo- and haloperidol
      (HAL)-controlled trial with 335 randomized subjects with chronic schizophrenia in
      an acute exacerbation, three fixed dose ranges of OLZ (5, 10, or 15 +/- 2.5 mg)
      were evaluated versus HAL (10-20 mg) or placebo. RESULTS: Baseline to endpoint
      change in the Brief Psychiatric Rating Scale including the anxiety-depression
      cluster (items 1, 2, 5, 9) was analyzed. Two dose ranges of OLZ (10 +/- 2.5, 15
      +/- 2.5) were superior to placebo (p < 05) in improving mood status, whereas HAL
      was not. CONCLUSION: Contributions from a more selective mesolimbic dopaminergic
      profile, D1 or D4 activity, the release of dopamine/norepinephrine in the
      prefrontal cortex, and/or serotonin 5-HT2A,C antagonism may explain the
      differential benefit seen with OLZ in the treatment of comorbid anxious and
      depressive symptoms in schizophrenia.

PMID- 9611670
TI  - Effects of ketamine on thought disorder, working memory, and semantic memory in
      healthy volunteers.
AB  - BACKGROUND: The N-methyl-D-aspartate receptor antagonist, ketamine, produces a
      clinical syndrome of thought disorder, perceptual distortion, and cognitive
      impairment. METHODS: We have administered ketamine to healthy volunteers to
      characterize the formal thought disorder and specific memory dysfunction
      associated with ketamine. Ten healthy volunteers underwent a double-blind,
      placebo-controlled, ketamine infusion (0.12 mg/kg bolus and 0.65 mg/kg/hour).
      Thought disorder was evaluated with the Scale for the Assessment of Thought,
      Language and Communication. Cognitive testing involved working and semantic
      memory tasks. RESULTS: Ketamine produced a formal thought disorder, as well as
      impairments in working and semantic memory. The degree of ketamine-induced
      thought disorder significantly correlated with ketamine-induced decreases in
      working memory and did not correlate with ketamine-induced impairments in
      semantic memory. CONCLUSIONS: This study characterizes the formal thought
      disorder associated with ketamine and may suggest that ketamine-induced deficits
      in working memory are associated with ketamine-induced thought disorder.

PMID- 9611671
TI  - Neuroendocrine and clinical characteristics of major depressed patients
      exhibiting sleep-onset REM.
AB  - BACKGROUND: Previous reports suggest an association between sleep-onset REM
      (SOREM) and some clinical characteristics in depressive illness such as age,
      psychosis, and depression severity. The present study is aimed at further
      investigating clinical and neuroendocrine correlates of SOREM, controlling for
      the age-related variability in clinical data. METHODS: Thyroid-stimulating
      hormone response to thyrotropin-releasing hormone, postdexamethasone cortisol
      levels, and clinical characteristics of 25 major depressive (MD) patients
      exhibiting SOREM in at least one of three consecutive recording nights were
      compared to those of 25 age- and sex-matched MD patients with three REM latencies
      above 50 min. RESULTS: SOREM patients experienced more affective episodes leading
      to hospitalization and a shorter duration of current episode than patients with
      three REM latencies above 50 min. No association between psychosis and SOREM
      could be demonstrated, and hypothalamic-pituitary-adrenal or -thyroid axis
      disturbances were not more prevalent in SOREM patients. CONCLUSIONS: Our results
      suggest that clinical history rather than cross-sectional clinical
      characteristics relates to the occurrence of SOREM in major depressed patients.

PMID- 9611672
TI  - Treatment of rapidly cycling bipolar patient by using extended bed rest and
      darkness to stabilize the timing and duration of sleep.
AB  - BACKGROUND: The modern practice of using artificial light to extend waking
      activities into the nighttime hours might be expected to precipitate or
      exacerbate bipolar illness, because it has been shown that modifying the timing
      and duration of sleep can induce mania in susceptible individuals. With this
      possibility in mind, we treated a patient with rapidly cycling bipolar illness by
      creating an environment that was likely to increase and to stabilize the number
      of hours that he slept each night. METHODS: We asked the patient to remain at bed
      rest in the dark for 14 hours each night (later this was gradually reduced to 10
      hours). Over a period of several years, his clinical state was assessed with
      twice-daily self-ratings, once-weekly observer ratings, and continuous wrist
      motor activity recordings. Times of sleeping and waking were recorded with sleep
      logs, polygraphic recordings, and computer-based event recordings. RESULTS: The
      patient cycled rapidly between depression and mania and experienced marked
      fluctuations in the timing and duration of sleep when he slept according to his
      usual routine, but his sleep and mood stabilized when he adhered to a regimen of
      long nightly periods of enforced bed rest in the dark. CONCLUSIONS: Fostering
      sleep and stabilizing its timing by scheduling regular nightly periods of
      enforced bed rest in the dark may help to prevent mania and rapid cycling in
      bipolar patients.

PMID- 9611673
TI  - Microsleep during partial sleep deprivation in depression.
AB  - BACKGROUND: Sleep deprivation (SD) exerts a beneficial effect on mood and sleep
      in about 60% of depressed patients usually followed by a relapse into depression
      after the recovery night. Short phases of sleepiness, especially naps in the
      early morning, may be responsible for this phenomenon. METHODS: To evaluate the
      effect of short, even ultrashort phases of sleep-microsleep (MS) during partial
      sleep deprivation (PSD) on mood, cognitive psychomotor performance (CPP), and
      sleep, an electroencephalograph (EEG) was continuously recorded over 60 hours in
      12 patients with major depression. Subjective mood was assessed by a visual
      analogue scale and CPP by a letter cancellation test. RESULTS: The results
      illustrate that in depressed patients during PSD the amount of MS is increased,
      predominantly in the early morning, which was subjectively unrecognized and not
      observed by nursing staff. Patients with a low cumulative amount of MS during PSD
      improved significantly in mood, CPP, and sleep pattern compared to the patients
      with a high amount of MS who showed only slight changes. CONCLUSION: Therefore,
      accumulated MS may influence the SD-induced positive effects in depressed
      patients.

PMID- 9611674
TI  - Sleep Deprivation in social phobia and generalized anxiety disorder.
AB  - BACKGROUND: Sleep deprivation has been shown to improve depressive symptoms in
      some patients with major depressive disorder, but it has not been tested in
      patients with generalized anxiety disorder (GAD) or social phobia (SP). METHODS:
      To determine if sleep deprivation altered anxiety or depressive symptoms in
      patients with GAD (n = 7) or SP (n = 8), we sleep deprived patients and normal
      controls (n = 18) for one night. RESULTS: On one measure of anxiety, GAD patients
      improved compared with controls, but there were otherwise no significant change
      differences between controls and SP or GAD patients. CONCLUSIONS: The lack of
      benefit is consistent with previous findings that sleep deprivation provides no
      benefit to patients with other anxiety disorders. Sleep deprivation may be a
      biological intervention that distinguishes anxiety from affective disorders.

PMID- 9611675
TI  - Serotonin transporter gene and risk for bipolar affective disorder: an
      association study in Spanish population.
AB  - BACKGROUND: The serotonin transporter (5-HTT) is an important candidate gene for
      the genetic transmission of manic depressive illness. Many studies of patients
      with affective disorders have found abnormalities in serotonin metabolism and
      dysregulation of the transporter itself. In the present study, we hypothesize
      that genetic variation in the 5-HTT gene (17q11.1-17q12) may have an effect in
      the etiology of manic depression. METHODS: To test this hypothesis, we analyzed
      allele, genotype, and haplotype frequencies of two polymorphisms recently
      described in the 5-HTT gene (a variable number of tandem repeats in intron 2 and
      a deletion/insertion polymorphism in the transcriptional control region) in a
      sample of 88 patients with manic-depressive illness and 113 controls. Cases and
      controls were matched for ethnic and geographic origin. RESULTS: No associations
      were found between any of these polymorphisms, tested individually or as
      haplotypes, and manic depression. Moreover, the genetic analysis by sex,
      presence/absence of psychiatric family history, and age of onset did not reveal
      significant differences in allele or genotype distributions. CONCLUSIONS: Our
      results suggest that the genetic variability of the 5-HTT gene is not a major
      risk factor for manic depression.

PMID- 9611676
TI  - Gauging the effectiveness of extended imipramine treatment for panic disorder
      with agoraphobia.
AB  - BACKGROUND: Imipramine has proven efficacy for panic disorder. This study
      assesses the net effectiveness of systematic, open imipramine treatment in a
      homogenous sample of panic disorder patients with agoraphobia. METHODS: One
      hundred and ten consecutive patients with DSM-III-R moderate to severe panic
      disorder with agoraphobia were treated with a fixed regimen of imipramine 2.25
      mg/kg/day for 24 weeks. No instructions or encouragement for self-directed
      exposure to phobic situations or other coping strategies with panic or fear were
      given. Assessments were conducted at the end of the 2-week placebo run-in and at
      weeks 8, 16, and 24 of treatment. RESULTS: Overall, 53% had a marked and stable
      response. Most measures revealed that substantial improvement continued beyond
      week 8 of treatment. Treatment success was accompanied with significant
      improvements in anxiety sensitivity, dysphoric mood, and functional well-being.
      CONCLUSIONS: These results provide a clinically relevant reference with which to
      compare the effectiveness of alternative treatments in providing nearly complete
      symptom remission in patients with primary panic disorder with agoraphobia.

PMID- 9611677
TI  - Predictors of cortisol and 3-methoxy-4-hydroxyphenylglycol responses in the acute
      aftermath of rape.
AB  - BACKGROUND: Prospective studies of trauma survivors can provide information about
      the relationship between rape characteristics and the development of subsequent
      symptoms. METHODS: The present study examined the relationship of prior assault,
      rape severity, posttraumatic stress disorder (PTSD) symptoms following rape, and
      subsequent PTSD diagnosis, to the acute cortisol and 3-methoxy-4
      hydroxyphenylglycol (MHPG) response to this traumatic event in 20 women. RESULTS:
      Women with a history of prior physical or sexual assault showed a significantly
      attenuated cortisol response to the acute stress of rape compared to women
      without such a history. MHPG appeared to be associated with injury-related rape
      characteristics, and symptoms of active avoidance, but not prior history. PTSD
      status at the 3-month follow-up was predicted by both a prior history of assault
      and high injury rape, but was not directly predicted by either cortisol or MHPG
      levels. MHPG and cortisol were not correlated in the sample as a whole, but were
      correlated among individuals who did not subsequently develop PTSD (p = .04)
      CONCLUSIONS: The results suggest that different neuroendocrine systems may
      mediate different components of the response to traumatic stress.

PMID- 9611678
TI  - Epidemiology of tick-borne encephalitis in Japan.
AB  - A tick-borne encephalitis (TBE) patient has not been reported for many years in
      Japan although a serological survey of domestic animal sera suggested the
      presence of TBE foci in Hokkaido, the northern island of Japan. In October 1993
      in Hokkaido, a severe encephalitis case in a farm wife was diagnosed as tick
      borne encephalitis. Serological examination of paired sera showed a rise of
      neutralization (NT) antibody titer to Russian spring summer encephalitis virus. A
      sero-epizootiological survey of dogs showed that the TBE-related virus was
      prevalent in the area. Three virus isolates were obtained from the blood of
      sentinel dogs and the antigenic analysis grouped the isolates into TBE-related
      viruses. Sequence analysis of envelope protein gene identified one of the
      isolates as the same subtype as Russian spring summer encephalitis (Far-Eastern
      TBE) virus. The results provide the evidence that TBE is endemic in a certain
      area of Japan.

PMID- 9611680
TI  - Antistriational antibodies during Toxocara canis, Trichinella spiralis
      infections.
AB  - The parasitic infections (Toxocara can is, Trichinella spiralis) are
      characterized by general and local symptoms including fever, muscle pain and
      swelling. The question was asked whether the muscle changes that occur due to
      larva migrans give rise to the autoimmune response. The presence of
      antistriational antibodies (aStrAbs) was determined in the following groups of
      patients: group 1--66 patients with toxocariasis and the presence of anti
      Toxocara antibodies, group 2--22 patients suspected of Toxocara canis infection
      without anti-Toxocara antibodies, group 3--20 patients with active trichinellosis
      confirmed by anti-Trichinella antibodies. As control 25 healthy persons (group 4)
      were studied. The aStrAb were tested by the indirect fluorescence using unfixed
      cryostat sections of human striated muscle. The following results were obtained:
      group 1--42 sera positive, group 2--5 sera were weakly positive, group 3--all
      sera showed the presence of aStrAbs, group 4--no aStrAbs. The presence of aStrAbs
      in patients with parasitic infections may suggest the occurrence of anti-muscle
      autoimmune response.

PMID- 9611679
TI  - Immunizing effect of vaccinia virus expressing the nucleoprotein of rinderpest
      virus on systemic rinderpest virus infection in rabbits.
AB  - A recombinant vaccinia virus (RVV) expressing the nucleoprotein (NP) of
      rinderpest virus (RPV) was examined in rabbits for the involvement of the NP
      protein in protection from the RPV infection. Despite their production of anti-NP
      antibody, the RVV-immunized rabbits succumbed to the RPV challenge, although
      there was a slight delay in the onset of disease after the low-dose challenge. On
      the other hand, the animals immunized with RVV expressing the hemagglutinin (H)
      protein of the RPV were completely protected. These results indicate that the NP
      protein might be not so effective as the H protein for the protection against
      viremic and systemic infection with RPV.

PMID- 9611681
TI  - Serosurvey of Toxoplasma gondii in North Atlantic marine mammals by the use of
      agglutination test employing whole tachyzoites and dithiothreitol.
AB  - Serum samples from North Atlantic populations of harp seal, Phoca groenlandica (n
      = 316), ringed seal, Phoca hispida (n = 48), hooded seal, Cystophora cristata (n
      = 78), and minke whale, Balaenoptera acutorostrata (n = 202), were tested for
      Toxoplasma gondii-specific IgG. The modified agglutination test (MAT) was
      slightly modified to be more user-friendly by replacing the 0.2 M 2
      mercaptoethanol with 10 mM dithiothreitol. No positive samples were found at 1:40
      dilution.

PMID- 9611682
TI  - Epidemiosurveillance of antimicrobial compound resistance of Staphylococcus
      intermedium clinical isolates from canine pyodermas.
AB  - In a retrospective study, 131 Staphylococcus intermedius strains isolated from
      apparently healthy dogs, and 187 Staphylococcus intermedius strains isolated from
      dog pyodermas in the clinical microbiology laboratory at the National Veterinary
      School in Nantes, during three successive periods: 1986-87, 1992-93 and 1995-96,
      were investigated and compared for their antimicrobial susceptibility. Results
      indicated that 60% to 65% of the strains were susceptible to Chloramphenicol and
      Doxycyclin, 65% to 80% of the strains were susceptible to macrolides
      (Erythromycin, Lincomycin and Clindamycin) and to Trimethoprim/Sulfonamide
      association. More than 95% of the strains were susceptible to three betalactamins
      tested: Oxacillin, Amoxycillin/Clavulanic acid, Cephalexin, to Gentamicin, to
      Fucidic Acid and to two quinolones: Enrofloxacin and Marbofloxacin. This last
      group is made up of choice antibacterials for the treatment of dog pyoderma. Many
      different resistance patterns were observed in each period with no really
      predominant profile, because of low plasmidic vs chromosomal balance of the
      genetic basis of antibacterial resistance in Staphylococcus intermedius. However,
      the proportion of multiresistant (> or = 3 drugs) strains increased from 10.8% in
      the first period, to 28% in the third period. This increased frequency of
      resistance suggests strongly that, as in Staphylococcus aureus human infections,
      the prescription of antibiotic compounds increases the prevalence of resistant
      strains.

PMID- 9611683
TI  - Actinobacillus pleuropneumonia serotype 2--effects on the interferon-alpha
      production of porcine leukocytes in vivo and in vitro.
AB  - Effects of a bacterial infection on the IFN-alpha production in vivo and in vitro
      were studied in eight specific pathogen free pigs experimentally infected with
      Actinobacillus pleuropneumoniae. Clinically, the experimental infection was
      manifested as a febrile stage which lasted approximately one week and by signs of
      respiratory disease. The Aujeszky's disease virus (ADV) induced IFN-alpha
      production, assessed in whole blood cultures, was increased for the infected pigs
      during the febrile stage. Potentiating effects on the IFN-alpha production could
      be transferred to cultures of purified peripheral blood mononuclear cells with
      sera collected from the infected pigs during this period of time. Although the
      experimental infection with A. pleuropneumoniae did not induce any detectable
      amounts of IFN-alpha in serum or nasal secretion, both a phenol-extract and a
      heat-inactivated preparation of the bacteria induced low levels of IFN-alpha in
      cultures of purified PBMC. The interferogenic structures of the bacteria were not
      identified but there were indications that the bacteria induced IFN-alpha
      production in the same cell type as ADV.

PMID- 9611684
TI  - Further investigations on the efficacy of a non-specific defence inducer
      evaluated in calves exposed to infectious bovine rhinotracheitis virus.
AB  - Six calves were given the immunomodulator Baypamun and housed together with
      another six calves of which, three were experimentally infected with bovine
      herpesvirus-1 (BHV-1), whereas the remaining three served as untreated controls.
      The three experimentally infected calves as well as the three controls developed
      clinical signs of the typical acute form of infectious bovine rhinotracheitis
      (IBR). Of the calves treated with Baypamun, those that had only one injection of
      the immunomodulator, either at the start of the experiment (time 0) or 2 days
      later, underwent a much milder form of IBR and recovered in a shorter time than
      the experimentally infected calves or the controls. The calves that received four
      injections of the immunomodulator, i.e. at time 0 and subsequently for the next 3
      days, remained healthy throughout the 30 days of observation. Moreover, the virus
      shedding by the Baypamun treated calves was significantly reduced. It was
      speculated that the use of an immunomodulator, eventually associated with a
      vaccination programme, would be a feasible approach to reduce significantly the
      onset of outbreaks of BHV-1, one of the main infectious agent initiating the
      respiratory disease in cattle.

PMID- 9611685
TI  - Pharmacological era in the treatment of sexual disorder.

PMID- 9611686
TI  - Oral treatment of erectile dysfunction: from herbal remedies to designer drugs.
AB  - The erect penis has always been a symbol of power, virility, and fertility.
      Inability to obtain or maintain an erection, known clinically as erectile
      dysfunction, is a major health problem. It can cause considerable distress,
      unhappiness, and relationship problems. The search has therefore continued from
      time immemorial to find an effective safe, and easy to administer treatment for
      erectile problems. Although a number of these treatments became available in the
      last two decades, they all had problems with efficacy, safety, or ease of
      administration. Clinicians in this field often are told at the end of an
      assessment interview, "I wish you have a magic pill". An effective and safe oral
      treatment is, no doubt, the most acceptable and easy to use option. Finding such
      a treatment has always been the dream of many scientists, and many attempts have
      been made over the years. These ranged from herbal remedies used by native
      healers, mostly in Eastern countries, to the more sophisticated designer drugs,
      which are based on a better understanding of the physiological mechanism of
      erection. This article describes some of these attempts.

PMID- 9611687
TI  - Effects of child and adult sexual abuse on adult sexuality.
AB  - The differential effects of child and adult sexual abuse on adult sexual
      functioning were examined. The Golombok Rust Inventory of Sexual Satisfaction
      (GRISS) and a sexual experiences questionnaire were administered to 201
      psychology students at the University of South Florida, 175 of whom were retained
      in the study. GRISS variables that were analyzed consisted of anorgasmia, sexual
      avoidance, sexual dissatisfaction, sexual noncommunication, nonsensuality, and
      vaginismus. Women who were sexually abused in adulthood were more sexually
      dissatisfied and nonsensual than women who had no history of sexual abuse. In
      addition, women who had a history of sexual abuse in childhood or adulthood were
      less satisfied with the overall quality of their most recent sexual relationship
      than non-abused women and had higher numbers of unsafe sexual partners.

PMID- 9611688
TI  - Commentary: effects of sexual trauma on adult sexuality.

PMID- 9611689
TI  - Age and gender differences in sexual behavior preferences: a follow-up report.
AB  - This study extends prior research on gender differences in sexual behavior
      preferences. The authors administered the 6-factors Inventory of Dyadic
      Heterosexual Preferences (IDHP)1 to 76 married or cohabiting couples (mean age =
      35 years). Their preference patterns were compared to similar data obtained
      previously from younger (mean age = 21 years), single respondents. Gender
      differences that were replicated included women's stronger preferences for
      romantic foreplay and men's greater erotophilia and preferences for using erotica
      and combining alcohol and drug use with sex. Women's stronger conventionality was
      not replicated among older partners, both of whom were less conventional than
      their younger counterparts. Older men and women were also more inclined toward
      the use of erotica. Unlike younger men, older men were more negative toward the
      use of contraception. Implications for sexual safety, adjustment, communication,
      and therapy are discussed.

PMID- 9611690
TI  - Sexual morality of Christianity.
AB  - After discussing the origin of religion, functions of religion, and the
      construction of meaning by religion, the author focuses on the connection between
      religion and anxiety. The permanent anxiety in religion is determined by guilt
      feelings that arise for example from the violation of norms in the area of
      sexuality. In a religion at enmity with sexuality, such as Christianity, the
      satisfaction of sexual desires is considered bad and sinful; the permanent
      production of anxiety and a guilty conscience are the result of it. Christian
      sexual suppression leads to the propagation of asceticism as the taming of
      corrupt sensuality that only religious virtuosi can maintain. One result of
      asceticism is celibacy, although passages from the Bible demand monogamy for
      bishops without prohibiting celibacy. In Catholicism, celibacy institutionalizes
      the enmity with sexuality and causes a permanent depreciation of real sexuality
      in favor of one projected onto the mother church and the Virgin Mary. A further
      consequence of asceticism is the reduction of sexuality to reproduction. In the
      section about the factual consequences of Christian sexual morality, the author
      connects sexual instinctual gratification with religious affiliation on the basis
      of an analysis of the sexual behavior of Germans. The weekly frequency rate of
      sexual intercourse amounts to 3.1 with male and female nondenominationals, 2.6
      with Protestants, and 2.3 with Catholics; 39% of nondenominational men, 20% of
      Protestant men, and 12% of Catholic men in Germany use condoms. The connection of
      religion and aggression is empirically significant as well. The religiously most
      active men feel more inclined to use aggression to reach sexual goals than
      religiously indifferent ones.

PMID- 9611691
TI  - Divorce after couple therapy: an overlooked perspective of outcome research.
AB  - This exploratory study provides data about couples that divorced following couple
      therapy and compares them with couples that remained together. The divorced
      couples differed from the nondivorced couples in age difference, complaint at
      intake, positive regard, and empathy at the start of therapy. Most of the couples
      found couple therapy useful and viewed their divorce as a positive result of
      therapy.

PMID- 9611692
TI  - Into the 21st century: renewing the campaign for school-based sexuality
      education.
AB  - School-based sexuality education (SBSE) has been controversial and has faced
      numerous challenges to its survival. However, as the 21st century approaches, new
      and more intense threats are surfacing. A reenergized campaign for SBSE is needed
      to overcome these obstacles. Part of this campaign is to explore new directions
      and devise new strategies for SBSE programs.

PMID- 9611693
TI  - Ginkgo biloba for antidepressant-induced sexual dysfunction.
AB  - In an open trial ginkgo biloba, an extract derived from the leaf of the Chinese
      ginkgo tree and noted for its cerebral enhancing effects, was found to be 84%
      effective in treating antidepressant-induced sexual dysfunction predominately
      caused by selective serotonin reuptake inhibitors (SSRIs, N = 63). Women (n = 33)
      were more responsive to the sexually enhancing effects of ginkgo biloba than men
      (N = 30), with relative success rates of 91% versus 76%. Ginkgo biloba generally
      had a positive effect on all 4 phases of the sexual response cycle: desire,
      excitement (erection and lubrication), orgasm, and resolution (afterglow). This
      study originated from the observation that a geriatric patient on ginkgo biloba
      for memory enhancement noted improved erections. Patients exhibited sexual
      dysfunction secondary to a variety of antidepressant medications including
      selective serotonin reuptake inhibitor (SSRIs), serotonin and nonrepinephrine
      reuptake inhibitor (SNRIs) monoamine oxidase inhibitor (MAOIs), and tricyclics.
      Dosages of ginkgo biloba extract ranged from 60 mg qd to 120 mg bid (average =
      209mg/d). The common side effects were gastrointestinal disturbances, headache,
      and general central nervous system activation. The article includes a discussion
      of presumed pharmacologic mechanisms, including effects on platelet activating
      factor, prostaglandins, peripheral vasodilatation, and central serotonin and
      norepinephrine receptor factor modulation.

PMID- 9611694
TI  - Waiting to explode: how women can manage anger.

PMID- 9611695
TI  - Anticipating HERS: questions from the Heart and Estrogen/Progestin Replacement
      Study.

PMID- 9611696
TI  - News from the Society for the Advancement of Women's Health Research. Targeting
      mental illness and substance abuse among women.

PMID- 9611698
TI  - Toward optimal health: the experts respond to urinary incontinence.

PMID- 9611697
TI  - Progress Report: the national strategic plan for the early detection and control
      of breast and cervical cancers.

PMID- 9611699
TI  - Bladder control requires active management.

PMID- 9611700
TI  - Breastfeeding and women's health.
AB  - Breastfeeding often is promoted mainly as an infant health issue, with little if
      any mention of its importance to the mother's health. Despite its significant
      impact on women's health, breastfeeding is rarely emphasized in women's health
      programs. This article reviews the current medical literature regarding women's
      health aspects of breastfeeding, including medical, psychosocial, and
      environmental issues. Strategies for increasing health care professionals'
      awareness and promotion of breastfeeding as a women's health issue are discussed
      in the hope of reversing the worldwide decline in breastfeeding.

PMID- 9611701
TI  - Agreement in assessing endometrial pathology: the Postmenopausal
      Estrogen/Progestin Interventions (PEPI) Trial.
AB  - We report on agreement in interpreting endometrial biopsy specimens between the
      local and central pathologists of the Postmenopausal Estrogen/Progestin
      Interventions (PEPI) trial. This trial was a 3-year, multicenter, randomized,
      double-masked, placebo-controlled trial of four groups taking estrogen or
      estrogen/progestin combinations. A total of 1804 follow-up biopsies were
      performed in 596 subjects. Relative sensitivity and relative specificity using
      the diagnosis from the central pathologist as the gold standard and overall
      agreement are presented. Almost 90% of the diagnoses were reported normal by both
      readers. There were significant differences in agreement among clinics and
      treatment arms (p < 0.0001). The visit at which the biopsy specimen was obtained,
      age at baseline, prior postmenopausal estrogen use, parity, and drug adherence
      were not associated with agreement between the two readers. Higher proportions of
      disagreement were seen in two clinics (13% and 11%) compared with the other five
      clinics (2%-5%). Biopsy specimens from participants who were taking conjugated
      equine estrogens (CEE) only were more likely to be diagnosed differently by both
      readers (11%) than biopsy specimens from women taking a placebo (2%) or CEE
      combined with progestins (5%). Relative specificity varied from 86.4% to 98.9%
      among the clinics (p < 0.0001). Relative sensitivity was based on a small number
      of diagnoses, as few biopsy specimens were classified abnormal by the central
      pathologist. In patients assigned to CEE combined with progestin, 5 of the 7
      biopsy specimens that were recorded abnormal by the central pathologist received
      a normal diagnosis locally. Our findings show that sample size requirements for
      study designs in which a central reader is used can be at least threefold lower
      than the requirements for designs relying on local diagnoses. Centralized
      protocols for endometrial histopathology reading and staff training are highly
      desirable in multicenter trials.

PMID- 9611702
TI  - Does diagnostic accuracy in mammography depend on radiologists' experience?
AB  - This study was designed to determine if radiologists' experience in mammography
      is associated with their performance in correctly interpreting mammograms. Study
      mammograms (n = 150) were chosen by stratified random sampling from those
      interpreted as normal, abnormal-benign or abnormal-suspicious for cancer, with
      oversampling of cancer cases. Ten radiologists who had varying amounts of
      experience were asked to read the mammograms. Associations between the levels of
      the radiologists' experience and their accuracy in reading mammograms were
      assessed. Significant associations (p < 0.05) were found between the frequency of
      immediate workup recommendations in cancer patients and obtaining feedback, total
      lifetime mammograms read, number of mammography continuing medical education
      (CME) credits, and practice type. Radiologists with more experience also noted
      smaller cancer lesions. However, these experience variables were also associated
      with increased workup recommendations in the noncancer patients (p < 0.10). In
      multivariable analysis, obtaining regular feedback and the total lifetime number
      of mammograms read were independently associate with the number of times
      immediate workup was recommended in the cancer cases. The most experienced
      radiologist had the highest sensitivity in diagnosing breast cancer. Further
      studies are needed to assess whether the current requirements of the U.S. Food
      and Drug Administration for radiologists who read mammograms ensure acceptable
      levels of accuracy.

PMID- 9611703
TI  - Differences in notifiable infectious disease morbidity among adult women--United
      States, 1992-1994.
AB  - By 1990, all 50 states were using the Centers for Disease Control and Prevention
      (CDC) National Electronic Telecommunications System for Surveillance to report
      individual case data that included demographic information (without personal
      identifiers) about most notifiable diseases. This analysis of National Notifiable
      Diseases Surveillance System (NNDSS) data is useful for evaluating the
      distribution of reported notifiable infectious diseases among adult women by age
      and race. The number of cases of the 48 nationally notifiable infectious diseases
      reported among adult women (i.e., women > or = 15 years of age) were compiled for
      1992-1994. These data were then analyzed by age and race, and rates per 100,000
      adult women were calculated. During 1992-1994, the 10 most commonly reported
      nationally notifiable diseases among adult women in the United States were, in
      descending order of frequency, gonorrhea, primary/secondary syphilis, acquired
      immunodeficiency syndrome (AIDS), salmonellosis, tuberculosis, hepatitis A,
      hepatitis B, shigellosis, Lyme disease, and hepatitis C/non-A non-B. Gonorrhea
      was the most commonly reported notifiable infectious disease for women of all
      ages, except those ages > or = 55 years, and for women of all races, except
      Asian/Pacific Islanders. Tuberculosis was the most commonly reported infectious
      disease among women of Asian/Pacific Island descent. Analysis of NNDSS data
      provides information about the relative reported burden of diseases among women
      of all ages and different races. This information may be used for targeting
      research, prevention, and control efforts.

PMID- 9611704
TI  - A study of risk factors for ruptured tubal ectopic pregnancy.
AB  - Ruptured ectopic pregnancy is a leading cause of maternal mortality in the United
      States. The purpose of this study was to identify predictors of tubal rupture. A
      retrospective chart review of 236 ectopic pregnancies in 215 patients treated at
      the Cleveland Clinic Foundation from 1983 through 1996 was performed. Patients
      were stratified by rupture status of the ectopic pregnancy and compared for the
      following parameters: age, gravida, parity, aborta, gestational age, preoperative
      and postoperative hemoglobin level, need for blood transfusion, serum human
      chorionic gonadotropin (hCG) levels, and findings on ultrasonogram and at
      surgery. We also compared the two groups in multiple risk factors for ectopic
      pregnancy. We used the generalized estimating equation (GEE) methodology and
      unbalanced repeated measures analysis of variance to compare the two groups.
      Tubal rupture was found in 26.3% of ectopic pregnancies. Tubal rupture occurred
      with any serum hCG level, even with those under 100 mIU/ml. There was no
      significant difference between the two groups in gestational age, serum hCG
      levels, or ultrasound findings except that the frequency of ruptured pregnancies
      increases as the fluid amount documented on ultrasonography increases (p <
      0.001). There was no association between any of the risk factors or the number of
      risk factors and frequency of tubal rupture. There was no significant decrease in
      the rupture rate over time (p = 0.34). There was an increased morbidity
      associated with tubal rupture. Tubal rupture cannot be predicted on the basis of
      any known risk factor, ultrasonogram findings, or serum hCG levels. Early
      diagnosis and treatment of ectopic pregnancy are the only modality available to
      prevent tubal rupture and its associated morbidity.

PMID- 9611705
TI  - Physicians must ask about cardiovascular risk in postmenopausal women.

PMID- 9611706
TI  - Infertility treatment in women over 40 years of age.

PMID- 9611707
TI  - Prevalence and natural history of female incontinence.

PMID- 9611709
TI  - Viable offsprings derived from fetal and adult mammalian cells.

PMID- 9611708
TI  - Case report: Endometrial carcinoma after endometrial resection for menorrhagia.

PMID- 9611710
TI  - Literature watch.

PMID- 9611711
TI  - [Expression of different HIV-1 phenotypic subpopulations through the natural
      history of the infection].
AB  - BACKGROUND: Multiple viral subpopulations coexist in an HIV infected patient with
      dynamics of selection established between them. In order to get insight on the
      phenotype of these subpoblations, and its relation with disease progression, we
      have studied the biological variability of HIV-1 in 113 patients. Variability was
      related with CD4+ T lymphocyte counts, clinical status, way of viral transmission
      and antiretroviral treatment. PATIENTS AND METHODS: 113 patients (80 adults and
      33 children) were studied for HIV-1 isolation in cocultures of infected and non
      infected lymphocytes. Viral replication was evaluated as rapid (R)/slow (S) or
      high (H)/low (L). Syncytia formation was estimated in MT2 cell line (SI/NSI). The
      tropism toward lymphocytes and monocytes (LM) was studied on H9 and U937 cell
      lines. RESULTS: Up to 86.7% of viral isolates were R, 56.6% were H and 49.6% were
      SI. These percentages increased with disease progression. Eight viral strains
      were R/H/NSI cocultivated in MT2 cells and SI in cocultured lymphocytes (NSI/SI),
      which may be considered as a new phenotype. All the SI isolates and all the R/H
      (SI and NSI) isolates were LM. Three categories were established: R/H/SI/LM,
      R/H/NSI/LM and S/L/NSI/NLM. The first two categories corresponded to patients
      with CD4+ T lymphocytes <200 x 10(6)/I (56%, 50%). The third category
      corresponded to patients with > 500 x 10(6)/I (53.3%). CONCLUSIONS: Viral
      replication and SI phenotype, independently, are useful markers for severity of
      HIV infection. The biological differences among NSI of the 3 viral phenotype
      categories, including the new subgroup NSI/SI, may indicate the existence of more
      pathogenic NSI subpopulations.

PMID- 9611712
TI  - [High altitude pulmonary edema. Study of 21 cases].
AB  - BACKGROUND: The effect of altitude on subjects between 8 to 22 and 23 to 51
      years, that resided at sea level, or in the highlands, and developed altitude
      lung edema, is presented in series of 21 prospective registered patients at 4,800
      to 5,000 m altitude in the Andes mountains of Ecuador. PATIENTS MATERIAL AND
      METHODS: The 21 sick patients were evaluated at 2 h and at 8 hr after exposition
      to the high altitude. They were immediately evacuated from the high altitudes.
      Clinical and radiological methods were used. The statistical analysis was
      performed with chi(2) test with Yates correction and relative risk. RESULTS: The
      younger patients tended to develop illness with a higher frequency (p < 0.01).
      The place of residence influenced the development of the illness only for the
      group of persons between the ages of 23 to 51 years (p < 0.03); and also in
      comparing all of the subjects from the coast with those from the highlands.
      CONCLUSIONS: A inverse relationship was found between the age and the possibility
      of the development of altitude pulmonary edema, possibly due t a basic
      incrementation of the pressure of the pulmonary artery, or because of a relative
      immaturity of the adaptative mechanisms. The place of residence was significantly
      associated with a higher frequency of pulmonary edema in persons between the ages
      of 23 to 51 years.

PMID- 9611713
TI  - [Need for systematic HIV serological study during pregnancy].
AB  - BACKGROUND: To evaluate human immunodeficiency virus (HIV) screening usefulness
      in pregnancy and to know the prevalence of this infection in an urban area of
      Spain. PATIENTS AND METHOD: Routine prenatal screening for antibodies to HIV was
      offered to pregnant women from Fuenlabrada-Leganes Health Care Area (Madrid) from
      1992 to 1995. Unlinked anonymous screening of HIV was done with the sera from
      women refusing the assay or if it had not been offered. RESULTS: HIV prevalence
      was 0.28% (CI: 95%; 0.19 to 0.40) in the 11.021 pregnant women group studied.
      87.1% pregnant seropositive women were detected by consented screening. 55.6% of
      them recognized risk behavior (73.33% by intravenous drug use) and 44.4% did not
      do it. With a second anamnesis in this group 75% admitted risk conducts and 25%
      confirmed their ignorance about them. CONCLUSIONS: HIV seropositive screening in
      pregnant women selected only by risk behavior may be unsuccessful. For that
      reason, it is more convenient the perform a routine test for detection of HIV
      antibodies after informed consent in high prevalence areas of HIV infection.

PMID- 9611714
TI  - [Quantification of HIV-1 viral load by the measurement of reverse transcriptase
      activity].

PMID- 9611715
TI  - [A problem of altitude].

PMID- 9611716
TI  - [High altitude retinal hemorrhages in the expeditions to 8,000 meter peaks. A
      study of 10 cases].
AB  - BACKGROUND: Retinal haemorrhages are common at high altitude. Their pathogenesis
      is unknown. It has been suggested that they are less frequent in sherpas, and
      that possible predisposing factors might be the abscence of previous high
      altitude experience, the extent of the high-altitude hypoxic exposure,
      polycythemia (because of hyperviscosity), history of cough and Valsalva
      manoeuvres during the expedition, existence of severe forms of mountain sickness
      (high-altitude pulmonary oedema and high-altitude cerebral oedema) and use of
      antiinflammatory drugs. The aim of this study is to know the incidence of retinal
      haemorrhages in the expeditions to mountains higher than 8.000 m and their
      relationship to the previously referred possible predisposing factors. SUBJECTS
      AND METHODS: Funduscopy was performed on 17 healthy subjects taking part in
      expeditions to Cho-Oyu (8.201 m) and to Shisha Pangma (8.046 m) and on six of
      their Nepali coworkers. RESULTS: Retinal haemorrhages were found in 10 of the
      European (59%) and in none of the Nepali mountaineers (p = 0.019). Other 2
      Spanish climbers had tortuosity and engorgment of the retinal veins. No
      statistical association was found between retinal haemorrhages and maximal
      altitude attained prior to the expedition, maximal altitude reached during the
      present expedition, number of nights spent at extreme altitude, weight loss as an
      expression of chronic exposure to hypoxia, haemoglobin, history of cough or
      Valsalva manoeuvres during the expedition, existence of severe forms of mountain
      sickness or use of drugs. CONCLUSIONS: These results do not allow us to state
      that the mentioned factors predispose to high-altitude retinal haemorrhages.

PMID- 9611717
TI  - [Mountain sickness].

PMID- 9611718
TI  - [Hirsutism of 4 years of development in a 53 year-old patient].

PMID- 9611719
TI  - [Biliopleurobronchial fistula as a complication of hepatic hydatidosis].

PMID- 9611720
TI  - [Hypoglycemia secondary to ingestion of dextropropoxyphene in a drug addict
      patient].

PMID- 9611721
TI  - [The usefulness of the early notification of marked abnormal laboratory values in
      primary health care].

PMID- 9611722
TI  - [Aplastic anemia induced by albendazole].

PMID- 9611723
TI  - [Extrapyramidalism associated with the use of cisapride].

PMID- 9611724
TI  - [Dementia as the first manifestation of idiopathic hypoparathyroidism].

PMID- 9611725
TI  - [The clinical manifestations produced by Blastocystis hominis in childhood].

PMID- 9611726
TI  - [Evidence based medicine].

PMID- 9611727
TI  - [Hospital readmission in internal medicine departments].

PMID- 9611728
TI  - [Clinical, genetic and molecular studies on autosomal dominant polycystic kidney
      disease].
AB  - BACKGROUND: Two genes causing autosomal dominant polycystic kidney disease
      (ADPKD), PKD1 and PKD2, have been described. In the present work we study, by
      means of linkage analysis, the genetic heterogeneity in our population as well as
      the clinical differences between PKD1 and PKD2. SUBJECTS AND METHODS: 316
      subjects belonging to 49 unrelated ADPKD families have been studied by means of 3
      microsatellites for PKD1 and 3 for PKD2 to differentiate if they have ADPKD type
      1 or 2. The techniques used to analyze the microsatellites have been the
      chemiluminescence and the silver satining techniques. All the subjects underwent
      a complete physical examination and a sonographic scan. Clinical and molecular
      results have been correlated. RESULTS: Genetic heterogeneity has been proved,
      with 85% of families linked to PKD1 and 15% to PKD2. The disease is more severe
      in PKD1, with an earlier age at diagnosis (27.4 vs. 41.4 years; p = 0.0002), a
      younger age at the onset of end stage renal disease (53.4 vs. 72.7 years, p <
      0.00001), and earlier age at diagnosis of hypertension (34.8 vs. 49.7 years; p =
      0.001) and a higher prevalence of hypertension for all groups of age. In both
      forms of ADPKD there were families showing anticipation (8/44 for PKD1 and 2/5
      for PKD2) but this was not a widespread phenomenon. Our data do not support the
      phenomenon of genetic imprinting for this disease. CONCLUSION: In the population
      of Catalonia, Spain, PKD1 accounts for 85% of families with autosomal dominant
      polycystic kidney disease and PKD2 accounts for the remaining 15%. PKD1 form is
      more severe than PKD2.

PMID- 9611729
TI  - [Association between myocardial infarction and angiotensin converting enzyme gene
      polymorphism in young patients].
AB  - BACKGROUND: Different studies have shown a relationship between an insertion
      deletion polymorphism of the angiotensin converting enzyme (ACE) gene and the
      risk of ischemic heart disease, although there are no data on this association in
      the Spanish population. MATERIALS AND METHOD: We have studied three groups of
      patients: I, healthy volunteers (n = 56, mean age 36.20 +/- 4.20 years); II,
      patients having presented an acute myocardial infarction (MI) < or = 50 years (n
      = 59, mean age 42.30 +/- 5.30 years), and III, patients with MI over the age of
      50 years (n = 60, mean age 66.36 +/- 9.47 years). In all patients the genotype
      ACE gen was determined by an assay based on the polymerase chain reaction.
      RESULTS: The distribution of the ACE genotype between the three groups were not
      significative. Comparing the ratio of DD/II-DI in groups II and III there were
      26/33 versus 15/45 (p = 0.02864). There was no difference in the smoking,
      hypercholesterolemia and hypertension between groups II and III; there were only
      differences in familial history of ischemic heart disease; diabetes mellitus was
      more prevalent in the III group. A multivariate analysis showed that smoking
      familial history of ichemic heart disease, hypercholesterolemia and DD genotype
      were more prevalent in young patients (OR 3.92, 2.85, 2.36 and 1.77), whereas
      diabetes mellitus was more prevalent in the group of older patients. There were
      no differences in the ACE genotype with respect to infarct location or gender.
      CONCLUSIONS: In our population DD ACE genotype is associated with MI in young
      patients, although smoking, family history and hypercholesterolemia show a more
      powerful association.

PMID- 9611730
TI  - [Achondroplasia: molecular study of 28 patients].
AB  - BACKGROUND: The main goal of the study is to investigate in the Spanish
      population the value of searching for the Gly380Arg mutation in the transmembrane
      domain of fibroblast growth factor receptor-3 (FGFR3#) as the basis for the
      molecular diagnosis of achondroplasia. PATIENTS AND METHODS: Twenty eight
      achondroplastic patients were studied. Genomic DNA obtained from blood was used
      to amplify using PCR a 164 bp segment of FGFR3 encompassing the transmembrane
      domain. The occurrence of the G-->A transition and of the G-->C transversion at
      the first base of codon 380 were investigated by digestion with the restriction
      enzymes Sfcl and Mspl followed by electrophoretic analysis of the products.
      RESULTS: All achondroplastic patients were found to be heterozygous for the
      Gly380Arg mutation, as a consequence of the G-->A transition in 27 cases and of
      the G-->C transversion in the remaining patient. None of these changes were found
      in control subjects including a hypochondroplastic patient. CONCLUSIONS: The
      identification of the Gly380Arg mutation can be used in Spain for conclusive
      diagnosis of achondroplasia. The guanine at the first position of codon 380 of
      FGFR3 exhibits similarly increased frequency of mutation than in other
      populations, an thus it is unlikely that the genetic background of the population
      determines the mutation potential of this guanine.

PMID- 9611731
TI  - [About genes and disease].

PMID- 9611732
TI  - [Percutaneous endoscopic gastrostomy].

PMID- 9611733
TI  - [The Pro347Leu mutation of the rhodopsin gene in a Spanish family with autosomal
      dominant pigmentary retinosis].
AB  - We present a Spanish family affected with autosomal dominant pigmentary retinosis
      in which we have identified the mutation responsible for the disease (Pro347Leu)
      within the rhodopsin (RHO) gene. Complete ophthalmological and
      electrophysiological studies were performed in 14 members of this family. The
      molecular study, performed by SSCP analysis of the 5 exon and the promotor region
      of the rhodopsin gene, direct sequentiation and restriction analysis with the
      enzyme Mspl, showed a C-->T change in the second base of 347 codon of RHO gene.
      This mutation predicts a change of proline by leucine at this position. Every
      patient with the mutation showed a phenotype of diffuse, early onset and severe
      pigmentary retinosis with a little intrafamiliar variation. The Pro347Leu
      mutation, that has been very frequently described among all the populations, has
      been identified as a cause of RP in an Spanish family.

PMID- 9611734
TI  - [The pathogenesis of anemia associated with the human immunodeficiency virus
      (HIV) infection].

PMID- 9611735
TI  - [Questions regarding the chemoprophylaxis of tuberculosis].

PMID- 9611736
TI  - [Myositis: an unusual onset form of tuberculosis].

PMID- 9611737
TI  - [Tobacco habit in rural areas].

PMID- 9611738
TI  - [The evolution of premature mortality in Spain].

PMID- 9611739
TI  - [Facial diplegia by Epstein-Barr virus].

PMID- 9611740
TI  - [Deep vein thrombosis. An overdiagnosed process].

PMID- 9611741
TI  - [Choice of magnetic resonance tomographs by engineering and operating
      characteristics].

PMID- 9611742
TI  - [Programmed complex for planning fractionated regimens of malignant tumor
      irradiation by local adjustment of mathematical model parameters].
AB  - The accuracy of planning the fractionated radiation regimens may be enhanced by
      the proposed method of local adjustment of its parameters. For planning the
      fractionated radiation regimens in practical radiology, TDF was used to design a
      programmed complex (PC) which defines the main radiological parameters of a
      radiation plan as a system of interchangeable values in remote, contact, and
      combined radiation therapy for uniform and nonuniform dose fractionation
      regimens. PC allows a radiologist to actively use his clinical observation for
      local adjustment of mathematical model parameters and for planning the
      fractionated radiation regimens. The method of local adjustment of mathematical
      model parameters for dose fractionation is applicable to lung tissue radiation.
      Its advantage is that it permits one to consider the complexity of the organism
      exposed to radiation and, to a definite extent, to minimize the possible
      inadequacy of the used mathematical model of dose fractionation.

PMID- 9611743
TI  - [Experimental study of hydrodynamics of artificial heart valves].
AB  - The paper presents the results of examining the hydrodynamics of artificial heart
      valves (AHVs) manufactured in Russia and foreign countries. All the AHVs under
      study have been used in clinical practice for over 10 years and they are
      different in design. The hydrodynamics of AHVs was examined under static and
      pulsating flow through the valve. Photochromic imaging (PCI) was used for flow
      imaging. PCI is based on preparation of simulating blood (model physiological
      solution) in the medium, colour labels under laser radiation. The recording of
      colour label movement in the flow behind the valve using a speed camera makes it
      possible to follow flow hydrodynamics behind AHVs. The advantage of PCI over
      other methods is that the instant structure of flow behind the valve can be
      recorded just in the same section at any moment of an operating cycle. Based on
      the experimental data obtained by PCI, a procedure for comparative analysis of
      the hydrodynamic characteristics of AHVs was developed.

PMID- 9611744
TI  - [Rationale of noninvasive method of drug administration at the prelymphatic
      level].
AB  - The paper deals with the mode of local drug administration into the biological
      tissue at the prelympathic level without damaging the skin, which is based on
      enhancement of skin permeability by exposing to physical factors, including the
      use of contrast temperatures in the cyclic process of heating-cooling, followed
      by exposure to contact low-frequency ultrasound. Experimental and clinical
      studies of the mode versus routine drug administration have shown it to be
      promising in physiotherapeutic use.

PMID- 9611745
TI  - [Hydrodynamic and technological bases of a new design of the automyoneoventricle
      in assisted blood circulation].
AB  - The paper presents evidence for and results of development of a new hydrodynamic
      optimized design of the automyoneoventricle (AMNV) for extracorporeal circulation
      in critical myocardial lesions. The chosen geometry of externally spirally
      braided AMNV forms a curled flow that excludes the presence of eddy and stagnant
      zones which present a risk for thrombogenesis. Moreover, the paper details the
      original process for manufacturing the prototypes of the AMNV having spiral latex
      ribs, which has been modified to give its thromboresistant and antibiotic
      properties. The proposed biomechanical system has been put through tests yielding
      satisfactory results and it is to undergo clinical trials.

PMID- 9611746
TI  - [Pulse wave recording device].
AB  - The paper explains the causes of incorrect sphygmogram recording and describes
      the physical principle of a pulse wave recording device, its designing and
      technical features. Evidence is given for the advantages of pneumatic pressing
      over mechanic one, thereby enhancing the reproducibility and accuracy of pulse
      wave recording. Trials have indicated that the use of the proposed device needs
      much less time for making pulse diagnosis.

PMID- 9611747
TI  - [Amplitude-time and phase characteristics of pulse signal force transducer in
      multizone pulse diagnosis].
AB  - The paper provides numerical calculations of module-argument relationship of the
      transducing function of a pulse signal force transducer in the multiarea pulse
      diagnostic device to the parameters of the oscillation system. It is shown that
      free oscillations of the low-frequency oscillation system at 300 pi rad/c or more
      may yield allowable phase and amplitude-time distortions of signal A
      transduction, with real values of damping of a low-frequency part of the
      oscillation system, the noninformity of amplitude-time characteristics is no more
      than 30% in the working frequency range of the force transducer.

PMID- 9611748
TI  - [Role of cooperation of small enterprises in the production of rigid medical
      endoscopes].
AB  - The paper briefly describes the purposes and technical data of rigid endoscopes
      with grading optic elements designed and produced by 3 small enterprises which
      have common aims and methods of their fulfillment. It also gives brief
      characteristics of Russian gradanes used as objectives and translators of optic
      image. The experience of cooperation of small enterprises shows that not only a
      very large-scale optic enterprise, but an amalgamation of small enterprises may
      solve such a difficult problem as design and serial production of thin rigid
      endoscopes due to cooperation of all those having a required scientific-and
      technical potential.

PMID- 9611749
TI  - [Possibilities of myotonography].
AB  - The paper deals with the undamaging mode of examining the status of different
      elements of the human neuromuscular system, which is based on a task of test
      exposure and recording a response to it by recording rapid changes in the tension
      of appropriate muscles. Separately measured actual and imaginary constituents of
      complex tissue rigidity, which are recorded when a stamp vibrating at a fixed
      rate in the range of 10-100 Hz is pressed into them. The paper presents records
      of changes in the proposed characteristics of elastic and viscous properties of
      muscles in the following experiments: through external percutaneous electric
      stimulation of forearm muscles, through stimulation of knee reflex of the
      musculus quadriceps femoris, and through musculus gastrocnemius loading test.

PMID- 9611750
TI  - [Current and voltage kinetics of an autonomic electrostimulator of the
      gastrointestinal tract].
AB  - The paper presents experimental findings of the kinetics of current and voltage
      of a self-contained electric stimulator (SCES) of the gastrointestinal tract
      (GIT) with 12X18H9 stainless steel electrodes in 1% HCI solution (which mimics
      gastric juice). The structure and parameters of a dynamic SCES model are
      electrochemically considered. The model adequately describes experimental
      findings and may be used to generate capacity and Faraday components in the
      electrostimulation current at the electrode-electrolyte borders in order to
      evaluate the delivery of trace elements, which are deficient in the body, from
      the SCES electrodes into GIT on electrostimulation.

PMID- 9611751
TI  - [The M.V. Bekmetov--T.A. Khodzhimetov odontodynamometer].

PMID- 9611752
TI  - [The M.V. Bekmetov--T.A. Khodzhimetov periodontometer].

PMID- 9611753
TI  - [Genome fingerprinting in the epidemiology and epizootology of tuberculosis].
AB  - The history and modern status of tuberculosis are analyzed from epidemiological
      viewpoint. Different repeating genetic elements of mycobacterial genome are
      described, which have been recently used to develop methods for typing of
      pathogenic mycobacterial strains. Genome fingerprinting is compared with the
      traditional methods of epidemiology. The prevalence of Mycobacterium bovis in
      domestic and wild animals is analyzed.

PMID- 9611754
TI  - [Comparative analysis of antigens from different Brucella species using
      immunoblotting with antisera from immunized rabbits].
AB  - Brucella antigens recognized by IgG antibodies in cell lysates from various
      Brucella species differing by the origin, biological, and virulent properties
      (including the reference, vaccine, and newly isolated strains) were compared by
      sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Proteins in
      SDS-cell lysates were separated by 12% SDS-PAGE and protein gels were stained
      with Coomassie brilliant blue R-250 and Silver reagent. SDS-PAGE showed
      differences in the protein profiles of 15 strains of different species.
      Immunoblotting revealed that rabbit S-antisera contained IgG reacting with S-LPS
      and identical proteins of 90 to 16 kDa belonging to B, melitensis, B. suis, B.
      abortus, and B. neotomae strains. B. canis strains had 4 antigens reacting with
      these antisera, whereas B. ovis had none. No agglutinating antibody were detected
      by the standard tube agglutination test with smooth Brucella strains in rabbit R
      antisera. By contrast, immunoblotting analysis with these sera demonstrated
      common 90-16 kDa antigens in the strains of B. melitensis, B. suis, B. abortus,
      B. neotomae, and B. canis. B. ovis possessed none of these antigens. These
      results confirm that all Brucella species except B. ovis possess common protein
      antigens reacting with IgG.

PMID- 9611756
TI  - [COS-region of temperate coliphage N15].
AB  - The cohesive termini including the cos region (altogether 414 bp) of the DNA of
      the temperate coliphage N15 are sequenced. The termini are complementary 12
      nucleotide single-stranded 5'-extended DNAs. The sequence of the left terminus is
      5'-GGGCGGCGTCCG-3', that of the right 5'CGGACGCCGCCC-3'. Ten nucleotides of the
      N15 termini are identical to those of phage lambda. The N15 and lambda sequences
      are notably homologous only within the 50 bp region from the left and right ends.
      Phage N15 has a region with the nucleotide sequence identical to the R4 site of
      phage lambda, presumably reacting with terminase. This region is situated in the
      same site with regard to the cohesive sequence as in phage lambda. The cos region
      of N15 has no sequences similar to R1, R2, and R3 of lambda. N15 has a sequence
      similar to IHF of phage lambda, but in N15 this sequence is located near the
      right but not left (as in phage lambda) terminus. Computer analysis revealed
      palindromes and repeats within 450 bp of N15, including the cohesive termini.

PMID- 9611755
TI  - [Novel isoschizomers of restriction endonucleases from Pseudomonas aeruginosa
      strains].
AB  - Testing of Pseudomonas aeruginosa strains from the collection of the L. V.
      Gromashevsky Institute of Epidemiology and Infectious Diseases (Kiev) for
      specific endonucleases resulted in isolation of five class II restriction
      endonucleases, which were partially purified and their recognition targets were
      determined. Two of these endonucleases, Pae2kI and Pae18kI, are isoschizomers of
      Bg1II (5'-AGACTC-3'). Pae5kI and Pae14kI recognize the 5'-CCGC/GG-3' sequence and
      are therefore true isoschizomers of SacII. Hence, Pae17kI is an isoschizomer of
      PvuII and cleaves the DNA within the recognition sequence 5'-CAG/CTG-3'. Bg1II
      and PvuII are for the first time detected in Pseudomonas aeruginosa.

PMID- 9611757
TI  - [Primary structure of gene H of cattle plague virus strain K].
AB  - Synthesis, cDNA cloning, and identification of H gene nucleotide sequence of
      rinderpest virus (RPV) K strain are carried out. Analysis of the identified
      nucleotide sequence has revealed the single open reading frame encoding a protein
      consisting of 609 amino acids with molecular weight of 68 kDa. The mean
      nucleotide homology between H genes of K, Kabete O and L strains in 88.0%, the
      mean amino acid homology of the corresponding proteins is 88.2%. RPV K strain
      hemagglutinin contains 5 potential glycosylation sites. The position of all 13
      cystein bases is identical to positions in H proteins of RPV Kabete O and L
      strains. Studies of the hydrophobic profile of the compared proteins have shown 2
      potential transmembrane fragments.

PMID- 9611758
TI  - [Molecular basis of changes in biological properties of foot and mouth disease
      virus of subtype A22].
AB  - Primary structure of capsid proteins and RNA polymerase of three closely related
      strains of foot and mouth disease virus (FMDV), subtype A22, differing by
      biological properties (the initial epitheliotropic strain A22 550 and its
      derivatives: thermoresistant myotropic A22 550/4 and thermosensitive attenuated
      A22 645) are compared by nucleic acid sequencing and analysis of the amino acid
      sequencing. The study revealed 1 substitute in VPI and 8 in RNA polymerase in the
      myotropic variant and 1 substitute in VP2, 2 in VP3, 13 in VP1, and 3 in RNA
      polymerase. Alteration of A22 550/4 tropism is probably due to a single
      substitution Gly 145-->Thr in the RGD site of capsid protein VP1. Analysis of the
      origin and biological properties of the attenuated strain A22 645 and the results
      of studies of the primary structure of proteins permit us to hypothesize that
      attenuation is polygenic, caused by adaptation to a heterologous host (continuous
      porcine cell culture), and can be expressed by changes in the structure of virus
      antireceptor providing its binding to cell receptors. Sites responsible for the
      reproduction of A22 FMDV at certain temperatures are presumably located in RNA
      polymerase.

PMID- 9611759
TI  - [Isolation and cloning of gene for hepatitis delta antigen. The use of
      recombinant antigen for serodiagnosis of delta infection].
AB  - Hepatitis delta virus antigen was isolated from a patient by reverse
      transcription and polymerase chain reaction. Gel-purified cDNA was cloned in E.
      coli expression vectors. High expression of the recombinant HDAg in bacteria was
      observed. The minor and major forms of HDV antigens were simultaneously expressed
      in bacterial strains carrying SupE mutation. A laboratory method is developed for
      detecting anti-HD in patients' blood. It is based on the use of minor and major
      forms of recombinant HDV antigen immobilized on the same membrane filter. The
      method can be used for creating an original highly specific test system.

PMID- 9611760
TI  - [Isolation and specificity of novel restriction endonucleases Bsp40091 and AsiI,
      isoschizomers of BamHI].
AB  - New type II restriction endonucleases AsiI and Bsp40091 are detected in
      Azotobacter species N55 and Bacillus species 4009, respectively. Purified
      preparations of the restriction enzymes free from interfering nucleases and
      phosphatases were obtained by column chromatography on phosphocellulose and
      heparin-sepharose (Asil) and phosphocellulose and DEAE-cellulose (Bsp40091). The
      yield of purified AsiI and Bsp40091 was 16 x 10(3) and 8 x 10(3) units per g of
      wet cells, respectively. The above restriction endonucleases recognize the 5'-G
      decreases GATCC-3' sequence on double-stranded DNA and cleave it as shown, thus
      being true isoschizomers of BamHI restriction endonuclease.

PMID- 9611761
TI  - [Novel site-specific endonucleases from Brevibacterium species].
AB  - New site-specific endonucleases BecAI and BecAII have been detected in
      Brevibacterium species A. Endonuclease BecAII free from contaminating nonspecific
      endonucleases, exonucleases, and phosphatases was isolated by column
      chromatography on phosphocellulose, heparin sepharose, and DNA cellulose. It
      recognizes and cleaves the 5'-GG decreases CC-3' sequence and is a true
      isoschizomer of HaeIII restriction enzyme. The other restriction endonuclease,
      BecAI, cleaves Ad2 DNA at least by 2 sites but not the DNA of phage lambda, T7,
      SV40, phiX174, and plasmides pBR322 and pUC19. The substrate specificity of BecAI
      indicates its appurtenance to the super rare restriction endonucleases.

PMID- 9611762
TI  - Sample environments and techniques combined with small angle X-ray scattering.
AB  - The number of synchrotron radiation-based Small Angle X-ray Scattering beamlines
      has increased considerably over the last decade. With the high X-ray flux and
      collimation of these beamlines it not only has become possible to perform time
      resolved experiments on time scales down to the millisecond/frame range, but also
      it allows experimenters to utilise new sample environments and use simultaneous
      several experimental techniques on one sample. An overview of recent developments
      in this field is given.

PMID- 9611763
TI  - Polymerization on the rocks: theoretical introduction.
AB  - It is difficult if not impossible to synthesize long polymers of amino acids,
      nucleotides, etc., in homogeneous aqueous solution. We suggest that long polymers
      were synthesized on the surface of minerals in a prebiotic process analogous to
      solid-phase synthesis. Provided that the affinity of a mineral for an oligomer
      increases with the length of the oligomer, adsorption must become essentially
      irreversible for sufficiently long oligomers. Irreversibly adsorbed oligomers may
      be elongated indefinitely by repeated cycles in which the mineral with its
      adsorbed oligomers is first incubated with activated monomers and then washed
      free of deactivated monomer and side-products. We discuss in some detail the
      formation of oligomers of negatively-charged amino acids such as glutamic acid on
      anion-exchange minerals such as hydroxylapatite or illite. We show that the
      average length of adsorbed oligomers at steady state, n, depends on the balance
      between the rate of chain elongation and the rate of hydrolysis, and we derive a
      very approximate formula for n.

PMID- 9611764
TI  - Polymerization on the rocks: negatively-charged alpha-amino acids.
AB  - Oligomers of the negatively-charged amino acids, glutamic acid, aspartic acid,
      and O-phospho-L-serine are adsorbed by hydroxylapatite and illite with affinities
      that increase with oligomer length. In the case of oligo-glutamic acids adsorbed
      on hydroxylapatite, addition of an extra residue results in an approximately four
      fold increase in the strength of adsorption. Oligomers much longer than the 7-mer
      are retained tenaciously by the mineral. Repeated incubation of short oligo
      glutamic acids adsorbed on hydroxylapatite or illite with activated monomer leads
      to the accumulation of oligomers at least 45 units long. The corresponding
      reactions of aspartic acid and O-phospho-L-serine on hydroxylapatite are less
      effective in generating long oligomers, while illite fails to accumulate
      substantial amounts of long oligomers of aspartic acid or of O-phospho-L-serine.

PMID- 9611765
TI  - Polymerization on the rocks: beta-amino acids and arginine.
AB  - We have studied the accumulation of long oligomers of beta-amino acids on the
      surface of minerals using the 'polymerization on the rocks' protocol. We find
      that long oligopeptides of beta-glutamic acid which cannot be formed in
      homogeneous aqueous solution are accumulated efficiently on the surface of
      hydroxylapatite using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDAC) as
      condensing agent. The EDAC-induced oligomerization of aspartic acid on
      hydroxylapatite proceeds even more efficiently. Hydroxylapatite can also
      facilitate the ligation of the tripeptide (glu)3. The 'polymerization on the
      rocks' scenario is not restricted to negatively-charged amino acids.
      Oligoarginines are accumulated on the surface of illite using carbonyldiimidizole
      (CDI) as condensing agent. We find that FeS2 catalyzes the CDI-induced
      oligomerization of arginine, although it does not adsorb oligoarginines. These
      results are relevant to the formation of polypeptides on the primitive earth.

PMID- 9611766
TI  - Prebiotic amino acid thioester synthesis: thiol-dependent amino acid synthesis
      from formose substrates (formaldehyde and glycolaldehyde) and ammonia.
AB  - Formaldehyde and glycolaldehyde (substrates of the formose autocatalytic cycle)
      were shown to react with ammonia yielding alanine and homoserine under mild
      aqueous conditions in the presence of thiol catalysts. Since similar reactions
      carried out without ammonia yielded alpha-hydroxy acid thioesters (Weber, 1984a,
      b), the thiol-dependent synthesis of alanine and homoserine is presumed to occur
      via amino acid thioesters--intermediates capable of forming peptides (Weber and
      Orgel 1979). A pH 5.2 solution of 20 mM formaldehyde, 20 mM glycolaldehyde, 20 mM
      ammonium chloride, 23 mM 3-mercaptopropionic acid, and 23 mM acetic acid that
      reacted for 35 days at 40 degrees C yielded (based on initial formaldehyde) 1.8%
      alanine and 0.08% homoserine. In the absence of thiol catalyst, the synthesis of
      alanine and homoserine was negligible. Alanine synthesis required both
      formaldehyde and glycolaldehyde, but homoserine synthesis required only
      glycolaldehyde. At 25 days the efficiency of alanine synthesis calculated from
      the ratio of alanine synthesized to formaldehyde reacted was 2.1%, and the yield
      (based on initial formaldehyde) of triose and tetrose intermediates involved in
      alanine and homoserine synthesis was 0.3 and 2.1%, respectively. Alanine
      synthesis was also seen in similar reactions containing only 10 mM each of
      aldehyde substrates, ammonia, and thiol. The prebiotic significance of these
      reactions that use the formose reaction to generate sugar intermediates that are
      converted to reactive amino acid thioesters is discussed.

PMID- 9611767
TI  - Prebiotic chemistry of phosphonic acids: products derived from
      phosphonoacetaldehyde in the presence of formaldehyde.
AB  - Phosphonoacetaldehyde (PAL), a phosphonic acid analogue of glycolaldehyde
      phosphate, reacts in the presence of formaldehyde under mildly basic conditions
      to produce several new products. The reaction proceeds in two stages: a fast
      aldol condensation of formaldehyde with PAL, and a slower reaction to produce
      products containing two phosphonic acid groups. We report on the derivatization,
      isolation by means of HPLC and characterization of these compounds. One of the
      products is of potential interest as a building block for a prebiotic
      informational polymer.

PMID- 9611768
TI  - The role of self-assembled monolayers of the purine and pyrimidine bases in the
      emergence of life.
AB  - The experimental evidence for the spontaneous formation and structure
      determination of two-dimensional monolayers of the purine and pyrimidine bases is
      examined. The plausibility of such structures forming spontaneously at the solid
      liquid interface following their prebiotic synthesis suggests a functional role
      for them in the emergence of life. It is proposed that prebiotic interactions of
      enantiomorphic monolayers of mixed base composition with racemic amino acids
      might be implicated in a simultaneous origin of a primitive genetic coding
      mechanism and biomolecular homochirality. The interactions of these monolayers
      with carbohydrates and other derivatives is also discussed.

PMID- 9611769
TI  - Hydrogen consumption by methanogens on the early Earth.
AB  - It is possible that the first autotroph used chemical energy rather than light.
      This could have been the main source of primary production after the initial
      inventory of abiotic organic material had been depleted. The electron acceptor
      most readily available for use by this first chemoautotroph would have been CO2.
      The most abundant electron donor may have been H2 that would have been outgassing
      from volcanoes at a rate estimated to be as large as 10(12) moles yr-1, as well
      as from photo-oxidation of Fe+2. We report here that certain methanogens will
      consume H2 down to partial pressures as low as 4 Pa (4 x 10(-5) atm) with CO2 as
      the sole carbon source at a rate of 0.7 ng H2 min-1 microgram-1 cell protein. The
      lower limit of pH2 for growth of methanogens can be understood on the basis that
      the pH2 needs to be high enough for one ATP to be synthesized per CO2 reduced.
      The pH2 values needed for growth measured here are consistent with those measured
      by Stevens and McKinley for growth of methanogens in deep basalt aquifers. H2
      consuming autotrophs are likely to have had a profound effect on the chemistry of
      the early atmosphere and to have been a dominant sink for H2 on the early Earth
      after life began rather than escape from the Earth's atmosphere to space.

PMID- 9611770
TI  - Solar ultraviolet and the evolutionary history of cyanobacteria.
AB  - On the basis of photobiological, evolutionary, paleontological,
      paleoenvironmental and physiological arguments, a time course for the role of
      solar ultraviolet radiation (UVR, wavelengths below 400 nm) in the ecology and
      evolution of cyanobacteria is proposed in which three main periods can be
      distinguished. An initial stage, before the advent of oxygenic photosynthesis,
      when high environmental fluxes of UVC (wavelengths below 280 nm) and UVB (280-320
      nm) may have depressed the ability of protocyanobacteria to develop large
      populations or restricted them to UVR refuges. A second stage lasting between 500
      and 1500 Ma (million years), started with the appearance of true oxygen-evolving
      cyanobacteria and the concomitant formation of oxygenated (micro)environments
      under an oxygen free-atmosphere. In this second stage, the age of UV, the overall
      importance of UVR must have increased substantially, since the incident fluxes of
      UVC and UVB remained virtually unchanged, but additionally the UVA portion of the
      spectrum (320-400 nm) suddenly became biologically injurious and extremely
      reactive oxygen species must have formed wherever oxygen and UVR spatially
      coincided. The last period began with the gradual oxygenation of the atmosphere
      and the formation of the stratospheric ozone shield. The physiological stress due
      to UVC all but disappeared and the effects of UVB were reduced to a large extent.
      Evidence in support of this dynamics is drawn from the phylogenetic distribution
      of biochemical UV-defense mechanisms among cyanobacteria and other
      microorganisms. The specific physical characteristics of UVR and oxygen exposure
      in planktonic, sedimentary and terrestrial habitats are used to explore the
      plausible impact of UVR in each of the periods on the ecological distribution of
      cyanobacteria.

PMID- 9611771
TI  - Transforming growth factor-beta (TGF-beta).
AB  - The TGF-beta family of cytokines are ubiquitous, multifunctional and essential to
      survival. They play important roles in growth and development, inflammation and
      repair and host immunity. The mammalian TGF-beta isoforms (TGF-beta 1, beta 2 and
      beta 3) are secreted as latent precursors and have multiple cell surface
      receptors of which at least two mediate signal transduction. Autocrine and
      paracrine effects of TGF-beta's can be modified by extracellular matrix,
      neighbouring cells and other cytokines. The vital role of the TGF-beta family is
      illustrated by the fact that approximately 50% of TGF-beta 1 gene knockout mice
      die in utero and the remainder succumb to uncontrolled inflammation after birth.
      TGF-beta 2 and TGF-beta 3 gene knockout mice are not yet described. More
      recently, novel TGF-beta-like molecules have been described which share some of
      the properties of the mammalian TGF-beta isoforms. The role of TGF-beta in
      homeostatic and pathogenic processes suggests numerous applications in the
      diagnosis and treatment of various diseases characterised by inflammation and
      fibrosis.

PMID- 9611772
TI  - The CD44 protein family.
AB  - The designation CD44 describes a group of type I transmembrane proteins which
      share N-terminal and C-terminal sequences. These molecules differ in the central
      extracellular domain by the use of sequences encoded by ten variant exons which
      may be completely absent or included in various combinations and by cell type
      specific addition of glycosaminoglycan and carbohydrate moieties. Expression of
      variant proteins is observed in normal tissues such as on keratinocytes,
      dendritic cells and activated lymphocytes in the adult organism and on
      morphogenetically active epithelium such as the apical ectodermal ridge (AER) in
      the embryo. Certain CD44 proteins expressed on the AER can act as low affinity
      fibroblast growth factor receptors and are vital for epithelial-mesenchymal cell
      communication. CD44 variant proteins have also been implicated in tumour growth
      and metastasis and we speculate that CD44 mediated growth factor presentation may
      also be decisive in metastasis formation. Molecular strategies designed to block
      growth factor presentation by CD44 may aid in the therapy of metastatic cancer.

PMID- 9611773
TI  - The focal adhesion phosphoprotein, VASP.
AB  - Vasodilator-stimulated phosphoprotein (VASP) is associated with focal adhesions
      and areas of dynamic membrane activity, where it is thought to have an important
      role in actin filament assembly and cell motility. VASP contains a central
      proline-rich sequence which recruits the G-actin binding protein profilin.
      Localization of VASP to the leading edge of a migrating cell can lead to local
      accumulation of profilin, which in turn can supply actin monomers to growing
      filament ends. VASP binds to the focal adhesion proteins vinculin and zyxin and
      this probably directs the phosphoprotein to focal adhesions and the leading edge
      of stimulated cells. VASP functions as a binding intermediate between profilin
      and focal adhesion proteins. Intracellular pathogens, including Listeria
      monocytogenes, have coat proteins which bind VASP. This is one way in which these
      pathogens use VASP, and other proteins from the host cell, to assemble the actin
      filaments they require to move around the cytoplasm of infected cells and enter
      neighbouring cells. Understanding the role of VASP and other proteins in cell and
      bacterial motility is likely to lead to development of new therapeutic strategies
      for diseases including atherosclerosis and tumour growth, and for limiting the
      spread of intracellular pathogens.

PMID- 9611774
TI  - The role of glycosyl-phosphatidylinositol in signal transduction.
AB  - Glycosyl-phosphatidylinositol (GPI) lipids have a structural role as protein
      anchors to the cell surface. In addition, they are implicated in hormone, growth
      factor and cytokine signal transduction. Their phosphodiesteric hydrolysis
      mediated by an activated phospholipase results in the generation of water soluble
      oligosaccharide species termed the inositol phosphoglycan (IPG). This product has
      been demonstrated to possess biological properties when added exogenously to
      cells mimicking the biological effects of a variety of extracellular ligands.
      This may be accomplished since IPG is generic for a family of closely related
      species which are released in a tissue-specific manner and additionally have cell
      specific targets. Micro-organic synthesis has recently been able to shed new
      light on this topic by the introduction of defined oligosaccharide analogues of
      IPG for the assessment of their biological activity. These have complemented the
      findings observed with purified IPG from biological sources thus strengthening
      the belief that the GPI/IPG signalling system represents a truly novel aspect of
      transmembrane signalling.

PMID- 9611775
TI  - Ginsenoside Rh2 and Rh3 induce differentiation of HL-60 cells into granulocytes:
      modulation of protein kinase C isoforms during differentiation by ginsenoside
      Rh2.
AB  - Ginsenoside Rh1 or Rh2 differentiated B16 melanoma or F9 teratocarnoma to
      phenotypic normal melanocyte-like cells or parietal endoderm-like cells.
      Ginsenoside Rh3 and Rh4 were recently isolated from Panax ginseng, but their
      biochemical and pharmacological effects remain unidentified. The present study
      investigated whether the ginsenoside Rh group (G-Rh1, -Rh2, -Rh3 and -Rh4) having
      similar structures induce differentiation of HL-60 cells and whether protein
      kinase C (PKC) is involved in differentiation by ginsenoside. Differentiation was
      assessed by Wright-Giemsa stain and nitroblue tetrazolium reduction. G-Rh2 and G
      Rh3 induced differentiation of HL-60 cells into morphologically and functionally
      granulocytes but G-Rh1 and G-Rh4 did not. G-Rh2 and G-Rh3 arrested the cell cycle
      at the G1/S phase, consistent with the ability to induce differentiation in a
      decreasing order of retinoic acid > G-Rh2 > G-Rh3. During differentiation by G
      Rh2, Ca2+/phospholipid-dependent PKC activity was increased in both the cytosol
      and total cell extract and Ca2+/phospholipid-dependent phosphorylation of 38 and
      200 kDa endogenous proteins increased, while phosphorylation of 60, 64, 66 and 97
      kDa proteins was Ca2+/phospholipid-independent. When cytosolic PKC isoforms were
      analyzed by immunoblotting, no significant change was observed in the alpha
      level, however, the immunoreactive 60 kDa band of a similar mass to the PKC
      catalytic fragment appeared following treatment with G-Rh2. The beta isoform was
      gradually increased with prolonged treatment. The gamma isoform was not detected
      in the cytosol of untreated cells, whereas a small amount was detected 5 days
      after treatment. It is concluded that G-Rh2 and G-Rh3 can induce differentiation
      of HL-60 cells into granulocytes and modulation of PKC isoform levels may
      contribute to differentiation of HL-60 cells by G-Rh2.

PMID- 9611776
TI  - Ostrich intestinal glycohydrolases: distribution, purification and partial
      characterisation.
AB  - Intestinal glycohydrolases are enzymes involved in assimilating carbohydrate for
      nutrition. The avian forms of these enzymes, in particular the maltase
      glucoamylase complex (MG), are not well characterised. This study encompassed
      characterisation of these enzymes from ostrich intestines, and the first kinetic
      analysis of an avian MG. Proteolytically solubilised MG from ileal brush border
      membrane vesicles was purified by Sephadex G-200 gel filtration and Tris-affinity
      chromatography, while jejunal sucrase-isomaltase (SI) and MG were purified by
      Toyopearl-Q650 and phenyl-Sepharose chromatography. Amino acid sequences and
      compositions of enzyme subunits, resulting from SDS-PAGE, were determined.
      Kinetics of hydrolysis of linear oligosaccharides was studied. Ostrich MG and SI
      showed the highest activity in the jejunum, followed by the ileum and duodenum.
      No lactase or trehalase activity could be detected. The jejunal MG and SI,
      resulting from brush-border membrane vesicles, could not be separated during
      purification. However, a minor form of ileal MG was purified using Sephadex G-200
      chromatography. Ileal MG contained three subunits of M(r) 145,000, 125,000 and
      115,000. Although the N-terminal amino acid sequences bear no homology to SI, the
      M(r) 115,000 subunit shows homology to porcine MG in both sequence and amino acid
      composition. The pH optimum of maltose-, starch- and isomaltose-hydrolysing
      activity was 6.5 and that of sucrose-hydrolysing activity 5.5. The
      glycohydrolases were most active at 58 degrees C, but were quickly denatured
      above 60 degrees C. Sucrose- and starch-hydrolysing activities were more
      thermostable than maltose- and isomaltose-hydrolysing activities. Kinetic
      parameters (K(m), kcat and kcat/K(m)) for the hydrolysis of
      maltooligosaccharides, starch and glycogen are reported for ileal MG. Maltotriose
      and maltotetraose displayed partial inhibition of ileal MG. The study revealed
      large similarities between ostrich SI and MG in charge, size, shape and
      hydrophobicity, based on their inseparability by several methods. Measurement of
      the specificity constants for maltooligosaccharide hydrolysis by ileal MG
      revealed less efficient hydrolysis of longer substrates as compared to maltose
      and maltotriose.

PMID- 9611777
TI  - Purification and characterization of a human bradykinin binding protein from
      inflammatory cells.
AB  - Bradykinin (BK) is a potent mediator with a broad spectrum of pharmacological and
      inflammatory actions which are exerted through cell surface receptors. We report
      here the affinity chromatographic purification of a novel 14 kDa BK binding
      protein from human blood neutrophils and also peripheral blood mononuclear cells
      (PBMC), 80% of which are lymphocytes. Radioreceptor crosslinking experiments
      using bifunctional crosslinkers and radiolabelled BK identified a 14 kDa protein
      in these cell types both on the cell surface, in glycerol purified plasma
      membranes and in detergent solubilized cell extracts. Purification by BK affinity
      chromatography from a variety of BK responsive human cell types i.e. CCD-16Lu
      lung fibroblasts, HL60 promyelocytes, U937 myelomonocytes and Jurkat T
      lymphocytes also demonstrated a 14 kDa protein. Purified material obtained from
      three different BK affinity columns all demonstrated three major proteins at 190,
      50 and 14 kDa when eluted with either excess BK or mild acid. Neutrophil
      fractions from detergent solubilized cell extracts contained an additional 150
      kDa protein when eluted with mild acid. Neutrophil and PBMC crude plasma membrane
      BK affinity column purifications yielded only a single 14 kDa protein.
      Radioreceptor dot assays of the purified neutrophil eluates containing the 14 kDa
      protein revealed specific binding to [125I]-BK with a 160 fold excess signal
      ratio over the original membrane extract. Our data indicates that we have
      successfully isolated a 14 kDa novel human BK specific binding protein expressed
      on the surface of inflammatory cells.

PMID- 9611778
TI  - Heterologous expression of human transketolase.
AB  - Transketolase belongs to the family of thiamin diphosphate dependent enzymes. The
      aim of this study was to establish a bacterial expression system for human
      transketolase in order to investigate the functional characteristics of mammalian
      transketolases. The level of recombinant human enzyme expressed in Escherichia
      coli was modest. Purification of recombinant transketolase and separation from
      the E. coli enzyme has been greatly simplified by means of a non-cleavable hexa
      histidine tag. The highest specific activity was 13.5 U/mg and the K(m) values
      were 0.27 +/- 0.02 and 0.51 +/- 0.05 mM for the substrates D-xylulose 5-phosphate
      and D-ribose 5-phosphate, respectively. Binding of cofactors to the apoenzyme
      showed the expected hysteresis. Without preincubation, the K(m) values for
      thiamin diphosphate and for Mg2+ were, respectively, 4.1 +/- 0.8 and 2.5 +/- 0.4
      microM, but after 1 h of preincubation these values were 85 +/- 16 nM and 0.74 +/
      0.23 microM. The kinetic constants are similar to those of the native enzyme
      purified from human erythrocytes. Despite the modest expression level the
      reported system is well suited to a variety of functional studies.

PMID- 9611779
TI  - Large conductance channel in plasma membranes of astrocytic cells is functionally
      related to mitochondrial VDAC-channels.
AB  - Large conductance anion channels with similar electrophysiological
      characteristics were found in plasma membranes and in outer mitochondrial
      membranes of various cell types. Although their large conductance and their
      peculiar voltage dependence point to a close relation, it was questioned whether
      they belong to the same family. We therefore compared some biochemical features
      of a plasmalemmal channel with those known from the mitochondrial channel.
      Current events were recorded from excised patches of plasma membranes of a rat
      astrocytic cell line (RGCN). The underlying channels exhibited a conductance of
      401 +/- 50 pS. Open probability was highest between +/- 10 mV and gradually
      approached zero beyond +/- 25 mV. Activity as induced by voltage ramps between +/
      40 mV appeared after a delay of up to several min. The delay could be reduced by
      bathing either side of the patch in an acidic Ringer solution (pH 6.2). 1 mM Al3+
      increased the open time at potentials more positive than 20 mV. 10 mM dextran
      sulfate (MW 8000) caused reversible flickering, increasing the closed
      probability. 4,4'-diisothiocyanatostilbene-2,2' disulfonic acid (DIDS) also
      caused a reversible flickering into the closed state, reducing the apparent
      single channel amplitude by up to 70% at 0.5 mM DIDS. Application of 5 mM ATP
      resulted in reversible blockade; ATP was more effective from the outside than
      from the inside (blocking activity 65% vs. 16% of the patches). We conclude that
      the large conductance anion channel from astrocytic cells displays
      electrophysiological and pharmacological characteristics that resemble those of
      VDAC (Voltage Dependent Anion Channel) from the outer mitochondrial membrane.

PMID- 9611780
TI  - Polyamine sulfonamides with NMDA antagonist properties are potent calmodulin
      antagonists and cytotoxic agents.
AB  - N1-Dansylspermine and related sulfonamides of the natural polyamines are very
      potent blockers of NMDA-type glutamate receptors. They exhibit pharmacological
      properties which were not predicted from the constituents of the conjugates.
      Cytotoxicity and calmodulin antagonism of N1-dansylspermine were especially
      impressive. Calmodulin antagonism implies that N1-dansylspermine prevents
      induction of ornithine decarboxylase and inhibits its own active uptake via the
      polyamine transport system. Structure-activity considerations demonstrated that
      an aromatic character of the substituent is not required; amide bond formation
      with an aliphatic sulfonic acid is sufficient to transform spermine into a highly
      toxic calmodulin antagonist. Cytotoxicity and calmodulin antagonism are
      properties which are intrinsic to spermine, but they are observed only at very
      high concentrations. Amide bond formation at N1 with a lipophilic residue appears
      to 'amplify' these normally latent properties. The use of polyamine conjugates
      structurally related to the amides described in this work for targeting tumours
      may be marred by their calmodulin antagonism.

PMID- 9611781
TI  - Receptor binding of an apolipoprotein E-rich subfraction of high density
      lipoprotein to rat and human brain membranes.
AB  - During nerve cell degeneration, cholesterol released from the degrading cells is
      conserved through the formation of a cholesterol-apolipoprotein (apo) E complex
      which is subsequently taken up by regenerating nerve cells. The aim of the
      present project was to identify the physiologically relevant lipoprotein receptor
      for this lipoprotein complex which has remained elusive. HDL was separated into
      apo E-rich and apo E-poor subfractions and labelled with [14C]-sucrose. Labelled
      apo E-rich HDL bound to rat brain membranes in a time- and ligand concentration
      dependent manner and was a saturable process. Essentially no binding occurred
      with [14C]-apo E-poor HDL or with free apo E. Binding was partially inhibited by
      low density lipoprotein (LDL) and by alpha 2-macroglobulin. These results provide
      new evidence that native apoE-rich HDL particles resembling those present in the
      brain bind to rat brain membranes and that the binding may be due, at least in
      part, to the LDL receptor and to the LDL-receptor related protein. Evidence was
      also provided for the presence of a receptor which binds [14C]-sucrose human apoE
      rich HDL in human brain. Characterisation of the receptor which mediates the
      uptake of cholesterol from HDL-like complexes by brain cells is important in
      understanding the role of apoE in the central nervous system and of the
      alterations which occur in disorders such as Alzheimer's disease.

PMID- 9611782
TI  - Adsorptive immobilization of submitochondrial particles on Fractosil.
AB  - (1) Submitochondrial particles prepared from beef liver mitochondria were
      immobilized on Fractosil, a porous form of silica, in order to stabilize their
      enzymatic activity. (2) The catalytic activity of succinate-cytochrome c
      reductase, an enzyme complex of the inner mitochondrial membrane, was followed in
      this study. Adsorption resulted in significant stabilization with a lowering of
      K(m) (app.) for succinate, in spite of mass transfer and diffusion limitations
      expected to occur in such a complex and heterogeneous system. An increase in
      catalytic potential was also observed upon immobilization. These observations,
      taken together, suggest that substantial degree of conversation of substrates to
      their respective products may be achieved by such immobilized preparations. (3)
      Positive cooperative interactions for binding of submitochondrial particles to
      the matrix was observed, apparently with two sets of sites, the second set
      indicating a much greater hill coefficient. (4) The present report indicates that
      adsorption with the use of a porous inorganic support such as Fractosil may
      provide a simple and efficient method of immobilization. Such preparations
      containing membrane enzymes in their native microenvironments would be useful for
      continuous catalytic transformations and also for construction of biosensors.

PMID- 9611783
TI  - Distributions of distances in information strings.
AB  - Distances between identical symbols in information strings (biological, language,
      computer programs (*.exe files) are described with a different precision with
      four distributions: exponential, Weibull, log-normal and negative binomial. The
      correlations are sometimes highly significant.

PMID- 9611784
TI  - Antimicrobial activity characterization in a heterogeneous group of compounds.
AB  - In this work we carry out a study of pattern recognition to detect the
      microbiological activity in a group of heterogeneous compounds. The structural
      descriptors utilized are the topological connectivity indexes. The methods
      followed are stepwise linear discriminant analysis (linear analysis) and
      artificial neural network (nonlinear analysis). Although both methods are
      appropriate to differentiate between active and inactive compounds, the
      artificial neural network is, in this case, more adequate, since it shows in a
      test set a prediction success of 98%, versus 92% obtained with linear
      discriminant analysis.

PMID- 9611785
TI  - Aqueous solubility prediction of drugs based on molecular topology and neural
      network modeling.
AB  - A method for predicting the aqueous solubility of drug compounds was developed
      based on topological indices and artificial neural network (ANN) modeling. The
      aqueous solubility values for 211 drugs and related compounds representing
      acidic, neutral, and basic drugs of different structural classes were collected
      from the literature. The data set was divided into a training set (n = 160) and a
      randomly chosen test set (n = 51). Structural parameters used as inputs in a 23-5
      1 artificial neural network included 14 atom-type electrotopological indices and
      nine other topological indices. For the test set, a predictive r2 = 0.86 and s =
      0.53 (log units) were achieved.

PMID- 9611786
TI  - Conformational analysis and a crystal structure of bupropion, an antidepressant
      with dopamine reuptake blocking activity.
AB  - A conformational analysis has been performed on the antidepressant bupropion
      using the MM3-92 program. In addition, the structure of the compound in the
      crystal state was obtained. There is good agreement between the computed global
      minimum and the structure observed by crystallography. The three-dimensional
      structure of the preferred conformer of bupropion is consistent with the three
      dimensional structures of other dopamine reuptake blockers such as cocaine, CFT,
      and methylphenidate.

PMID- 9611787
TI  - RECAP--retrosynthetic combinatorial analysis procedure: a powerful new technique
      for identifying privileged molecular fragments with useful applications in
      combinatorial chemistry.
AB  - The use of combinatorial chemistry for the generation of new lead molecules is
      now a well established strategy in the drug discovery process. Central to the use
      of combinatorial chemistry is the design and availability of high quality
      building blocks which are likely to afford hits from the libraries that they
      generate. Herein we describe "RECAP" (Retrosynthetic Combinatorial Analysis
      Procedure), a new computational technique designed to address this building block
      issue. RECAP electronically fragments molecules based on chemical knowledge. When
      applied to databases of biologically active molecules this allows the
      identification of building block fragments rich in biologically recognized
      elements and privileged motifs and structures. This allows the design of building
      blocks and the synthesis of libraries rich in biological motifs. Application of
      RECAP to the Derwent World Drug Index (WDI) and the molecular fragments/ building
      blocks that this generates are discussed. We also describe a WDI fragment
      knowledge base which we have built which stores the drug motifs and mention its
      potential application in structure based drug design programs.

PMID- 9611788
TI  - Bacterial alginate biosynthesis--recent progress and future prospects.

PMID- 9611789
TI  - Physical map of the genome of Oenococcus oeni PSU-1 and localization of genetic
      markers.
AB  - A physical map of the chromosome of Oenococcus oeni PSU-1 was constructed. This
      represents the first map for a strain of this species. A total of 37 restriction
      sites for the rare-cutting endonucleases Ascl, Fsel, Notl and Sfil were mapped on
      the chromosome, which was found to be circular with an estimated size of 1857 kb.
      Fragment order was determined using several approaches: analysis of partial and
      double digestions, two-dimensional pulsed-field gel electrophoresis, isolation of
      linking clones, and Southern hybridization with labelled restriction fragments
      both from PSU-1 and from O. oeni strain GM. Oenococcal genes alsS/alsD, mleA and
      mir, two phage attachment sites and recurrent sequences such as IS1165-like
      elements and rrn loci were located on the physical map. Specific fragments
      hybridizing with gene probes from Lactococcus lactis, Leuconostoc mesenteroides
      and Bacillus subtilis were also identified. The two ribosomal operons have been
      precisely located and their transcription direction determined.

PMID- 9611790
TI  - Rapid identification of urinary tract infection bacteria using hyperspectral
      whole-organism fingerprinting and artificial neural networks.
AB  - Three rapid spectroscopic approaches for whole-organism fingerprinting-pyrolysis
      mass spectrometry (PyMS), Fourier transform infra-red spectroscopy (FT-IR) and
      dispersive Raman microscopy--were used to analyse a group of 59 clinical
      bacterial isolates associated with urinary tract infection. Direct visual
      analysis of these spectra was not possible, highlighting the need to use methods
      to reduce the dimensionality of these hyperspectral data. The unsupervised
      methods of discriminant function and hierarchical cluster analyses were employed
      to group these organisms based on their spectral fingerprints, but none produced
      wholly satisfactory groupings which were characteristic for each of the five
      bacterial types. In contrast, for PyMS and FT-IR, the artificial neural network
      (ANN) approaches exploiting multi-layer perceptrons or radial basis functions
      could be trained with representative spectra of the five bacterial groups so that
      isolates from clinical bacteriuria in an independent unseen test set could be
      correctly identified. Comparable ANNs trained with Raman spectra correctly
      identified some 80% of the same test set. PyMS and FT-IR have often been
      exploited within microbial systematics, but these are believed to be the first
      published data showing the ability of dispersive Raman microscopy to discriminate
      clinically significant intact bacterial species. These results demonstrate that
      modern analytical spectroscopies of high intrinsic dimensionality can provide
      rapid accurate microbial characterization techniques, but only when combined with
      appropriate chemometrics.

PMID- 9611791
TI  - Division of the genus Enterococcus into species groups using PCR-based molecular
      typing methods.
AB  - Broad-range 16S rDNA PCR (BR-PCR) applied to DNA from 32 clinical enterococcal
      isolates and 12 other enterococci from a clinical reference collection followed
      by species-specific hybridization analysis identified 25 strains of Enterococcus
      faecalis and 19 Enterococcus species. Randomly amplified polymorphic DNA (RAPD)
      analysis using UPGMA clustering on the same material revealed four different
      clusters at a similarity level of 49%. Based on partial 16S rDNA sequence
      analysis of variable regions V4 and V9, it was possible to divide the 19 type
      strains specifying the genus Enterococcus into 12 different 16S rDNA species
      groups. The type strain distribution then served as a template for the analysis
      of the other 44 strains which were assigned to four different species groups (a
      d) based on their 16S rDNA motifs. There was good agreement with the RAPD
      clusters. Species group a was an individual species line containing 25 strains
      that were identified as E. faecalis. Group b also represented an individual
      species line of 12 strains identified as E. faecium. The remaining seven strains
      that formed species groups c and d could not be fully identified to species by
      this analysis. It was concluded that BR-PCR of 16S rDNA followed by partial
      sequence analysis of the PCR products is a reliable technique for the
      identification and classification of enterococci. Further division of unresolved
      species groups should be achievable if regions other than V4 and V9 of 16S rDNA
      are also analysed.

PMID- 9611792
TI  - Analysis of lipids reveals differences between 'Mycobacterium habana' and
      Mycobacterium simiae.
AB  - Fatty and mycolic acids and the pattern of glycolipids were studied in a
      collection of 34 strains of 'Mycobacterium habana' and in two strains of
      Mycobacterium simiae. Major glycolipids of these micro-organisms were assigned to
      the glycopeptidolipid (GPL) structural type, but both mycobacteria differed in
      the patterns obtained by TLC. The strains of 'M. habana' were separated into four
      groups (A-D), taking into account the presence or absence of several polar GPLs:
      group A contained GPL-I, GPL-II and GPL-III; group B contained GPL-I, GPL-II',
      GPL-II and GPL-III; group C contained GPL-II', GPL-II and GPL-III; group D did
      not contain any of these compounds. Fatty acids of both bacteria were similar,
      and ranged from 14 to 26 carbon atoms, hexadecanoic, octadecenoic and
      tuberculostearic acids being predominant. Mycolic acids were also similar by TLC
      and HPLC, and consisted of alpha-, alpha'- and ketomycolates. Partial structural
      analysis by MS carried out in strains 'M. habana' TMC 5135 and M. simiae ATCC
      25275T revealed that alpha- and ketomycolates ranged, in general, from 79 to 87
      carbon atoms, and alpha'-mycolates from 58 to 67 carbon atoms. The alpha- and
      ketomycolates belonged to several structural series, and minor variations were
      found between the two strain examined. The data obtained justified the synonymy
      between 'M. habana' and M. simiae but indicated, in turn, that the former can be
      distinguished on the basis of GPL analysis. Most strains of 'M. habana' can be
      defined by the presence of GPL-II and GPL-III, a finding that could be useful in
      the quality control of potential vaccine strains.

PMID- 9611793
TI  - Genetic diversity in the Mycobacterium tuberculosis complex based on variable
      numbers of tandem DNA repeats.
AB  - Genetic loci containing variable numbers of tandem repeats (VNTR loci) form the
      basis for human gene mapping and identification, forensic analysis and paternity
      testing. The variability of bacterial tandem repeats has not been systematically
      studied. Eleven tandem repeat loci in the M. tuberculosis genome were analysed.
      Five major polymorphic tandem repeat (MPTR) loci contained 15-bp repeats with
      substantial sequence variation in adjacent copies. Six exact tandem repeat (ETR)
      loci contained large DNA repeats with identical sequences in adjacent repeats.
      These 11 loci were amplified in 48 strains to determine the number of tandem
      repeats at each locus. The strains analysed included 25 wild-type strains of M.
      tuberculosis, M. bovis, M. africanum and M. microti and 23 substrains of the
      attenuated M. bovis BCG vaccine. One of the five MPTR loci and all six ETR loci
      had length polymorphisms corresponding to insertions or deletions of tandem
      repeats. Most ETR loci were located in intergenic regions where copy number may
      influence expression of downstream genes. Each ETR locus had multiple alleles in
      the panel. Combined analysis identified 22 distinct allele profiles in 25 wild
      type strains of the M. tuberculosis complex and five allele profiles in 23 M.
      bovis BCG substrains. Allele profiles were reproducible and stable, as
      demonstrated by analyses of multiple isolates of particular reference strains
      obtained from different laboratories. VNTR typing may be generally useful for
      strain differentiation and evolutionary studies in bacteria.

PMID- 9611794
TI  - Characterization of novel immunodominant antigens of Mycobacterium tuberculosis.
AB  - Seven novel antigens of Mycobacterium tuberculosis, which had previously been
      identified based on reactivity to sera from patients with tuberculosis, were
      characterized. Nucleotide sequence analysis of the genes encoding these seven
      antigens identified one of them as the FtsH and a second as the aminoimidazole
      ribotide synthase of M. tuberculosis. Antisera raised to the recombinant forms of
      each of these seven antigens were used to study the distribution of these
      proteins within mycobacterial species as well as to determine their subcellular
      localization and hydrophobicity. Four of the seven antigens were conserved only
      among pathogenic strains of mycobacteria. Of the seven proteins studied, FtsH and
      a second protein of unknown identity were localized in membranes. Two were
      cytosolic, while two others, which had a high proline contents, were tightly
      associated with the cell wall. One protein was secreted. This secreted protein
      could be identified by serum from a majority of tuberculosis patients but not BCG
      vaccinated individuals, suggesting its potential use in the immunodiagnosis of
      tuberculosis.

PMID- 9611795
TI  - Characterization of a haemolysin from Mycobacterium tuberculosis with homology to
      a virulence factor of Serpulina hyodysenteriae.
AB  - Scrutiny of sequence data from the Mycobacterium leprae genome sequencing project
      identified the presence of a gene encoding a 268-amino-acid polypeptide which is
      highly similar to a pore-forming haemolysin/cytotoxin virulence determinant,
      TlyA, from the swine pathogen Serpulina hyodysenteriae. Using degenerate
      oligonucleotide primers based on the TlyA sequences, the Mycobacterium
      tuberculosis homologue was amplified and this product was used to obtain the
      clone and sequence a 2.5 kb fragment containing the whole M. tuberculosis tlyA
      gene. tlyA encodes a 267-amino-acid protein with a predicted molecular mass of 28
      kDa. TlyA homologues were identified by PCR in M. leprae, Mycobacterium avium and
      Mycobacterium bovis BCG, but appeared absent in Mycobacterium smegmatis,
      Mycobacterium vaccae, Mycobacterium kansasii, Mycobacterium chelonae and
      Mycobacterium phlei. The M. tuberculosis gene appeared to be the first gene in an
      operon containing at least two other genes. Introduction of the M. tuberculosis
      tlyA gene into M. smegmatis using a mycobacterial shuttle expression plasmid
      converted non-haemolytic cells into those exhibiting significant haemolytic
      activity. Similarly, inducible haemolytic activity was observed in sonicated
      bacteria when tlyA was expressed as a His6-tagged fusion protein in Escherichia
      coli. tlyA mRNA was detected in both M. tuberculosis and M. bovis BCG using RT
      PCR, confirming that this gene is expressed in organisms cultured in vitro.

PMID- 9611796
TI  - Recombination between rRNA operons created most of the ribotype variation
      observed in the seventh pandemic clone of Vibrio cholerae.
AB  - Individual rrn operons and their flanking regions have been analysed in a study
      of the molecular basis of ribotype variation in the seventh pandemic clone of
      Vibrio cholerae. The genome of an early isolate of the seventh pandemic clone had
      nine rrn operons of which two were in tandem with other rrn operons. The site for
      BglI, the most discriminatory enzyme used for ribotyping, was found to be present
      in the 16S sequence of three of the operons of the earliest isolate. This site
      was observed to be gained or lost in specific operons in many later isolates,
      presumably by recombination, and this gave most of the ribotype variation.
      Additional rrn recombination events were uncovered by analysis of the 16S-23S
      intergenic spacers associated with each operon. Spacers of 431, 509, 607 and 711
      bp were found. A total of at least eight rrn recombination events were detected.
      Three rrn loci were primarily involved in this recombination, with four new forms
      generated from that in the early strains for operon B and two new forms each for
      operons C and G. In addition there was variation due to deletion of tandem
      operons. The frequency of recombination between rrn operons was very high as
      there were nine new ribotypes found among 47 isolates sampled over the 33 year
      period of study. This means that any variation could undergo precise reversion by
      the same recombination event within the time frame covered by the study.
      Recombination between rrn operons may be a factor in ribotype variation in all
      systems. The recombination observed is thought to be that which results in
      concerted evolution and the data give an indication of the rate involved.

PMID- 9611797
TI  - Identification and analysis of a gene (abpA) encoding a major amylase-binding
      protein in Streptococcus gordonii.
AB  - Oral streptococci such as Streptococcus gordonii bind the abundant salivary
      enzyme alpha-amylase. This interaction may be important in dental plaque
      formation and metabolism, thus contributing to the initiation and progression of
      dental caries and periodontal disease, the two most common plaque-mediated
      diseases. The conjugative transposon Tn916 was used to insertionally inactivate
      gene(s) essential to the expression of amylase-binding components of S. gordonii
      Challis, and a mutant deficient in amylase-binding (Challis Tn1) was identified.
      While wild-type strains of S. gordonii released both 20 kDa and 82 kDa amylase
      binding proteins into culture supernatants, Challis Tn1 expressed the 82 kDa but
      not the 20 kDa protein. The 20 kDa amylase-binding protein was isolated from
      culture supernatants of S. gordonii Challis by hydroxyapatite chromatography. A
      partially purified, functionally active 20 kDa protein was sequenced from blots,
      and the N-terminal sequence obtained was found to be DEP(A)TDAAT(R)NND. A novel
      strategy, based on the single-specific-primer polymerase chain reaction
      technique, enabled the gene inactivated by Tn916 to be cloned. Analysis of the
      resultant nucleotide sequence revealed an open reading frame of 585 bp,
      designated amylase-binding protein A (abpA), encoding a protein of 20 kDa (AbpA),
      immediately downstream from the insertion site of Tn916. This protein possessed a
      potential signal peptide followed by a region having identity with the N-terminal
      sequence of the 20 kDa amylase-binding protein. These results demonstrate the
      role of the 20 kDa protein in the binding of amylase to S. gordonii. Knowledge of
      the nature of amylase-binding proteins may provide a better understanding of the
      role of these proteins in the colonization of S. gordonii in the oral cavity.

PMID- 9611798
TI  - Biological functions of UDP-glucose synthesis in Streptococcus mutans.
AB  - A gene encoding glucose-1-phosphate uridylyltransferase (EC 2.7.7.9) was isolated
      from Streptococcus mutans. A cell extract of Escherichia coli expressing the
      cloned gene exhibited glucose-1-phosphate uridylyltransferase activity. The
      enzyme catalyses the conversion of D-glucose 1-phosphate and UTP into UDP-D
      glucose. Rabbit antiserum against the serotype-c-specific antigen did not react
      with autoclaved extracts from mutant cells in which the cloned gene was
      insertionally inactivated. The glucose content of the cell-wall preparation
      purified from the mutant was very much lowered, whereas there was no observable
      decrease in the content of rhamnose. When the mutant strain was grown in an
      acidic environment, its cell viability was much lower than that of the wild-type.
      These results suggest that UDP-D-glucose functions not only as an immediate
      precursor of the serotype-c-specific antigen of S. mutans (as a glucose donor for
      side-chain formation), but is also important for the organism's viability in
      environmental conditions of low pH.

PMID- 9611799
TI  - Identification of two glycosylated components of Mycoplasma penetrans: a surface
      exposed capsular polysaccharide and a glycolipid fraction.
AB  - Among the wall-less mycoplasmas only a few species have been identified with a
      capsule at their cell surface. Mycoplasma penetrans is a recently identified
      mycoplasma with unique morphology, isolated from HIV-infected patients. Using
      transmission electron microscopy, it was found that M. penetrans is surrounded by
      capsular material 11 nm (strain GTU-54-6A1) to 30 nm (strain HF-2) thick, which
      can be stained with ruthenium red and labelled with cationized ferritin. The
      polysaccharide composition of this capsule was indicated by its staining with
      periodic acid-thiocarbohydrazide silver proteinate and the abolition of ruthenium
      red staining of the cell surface by neuraminidase treatment. In addition,
      proteinase K treatment of the M. penetrans cells resulted in removal of the
      capsule, suggesting that polypeptides may contribute in anchoring it to the
      membrane or in its stability. Two different types of glycosylated material were
      detected in mycoplasma extracts by SDS-PAGE and periodic acid-Schiff staining.
      The first component was a high-molecular-mass material, which was heat- and
      proteinase-K-labile and which probably constitutes the capsular polymer. The
      other component was a low-molecular-mass glycolipid fraction, which was
      proteinase-K-, heat- and EDTA-resistant. The identification of a capsule at the
      M. penetrans cell surface is of particular interest for a mycoplasma which has
      been shown to adhere to various host cells and to penetrate into their
      intracellular compartments. The capsule may have significance in the pathogenesis
      of disease associated with infection by this organism.

PMID- 9611800
TI  - An antigenic protein gene of a phytoplasma associated with sweet potato witches'
      broom.
AB  - A gene encoding the major antigenic protein of phytoplasma associated with sweet
      potato witches' broom (SPWB) was cloned and analysed by screening the genomic
      library of SPWB phytoplasma with monoclonal antibodies for SPWB phytoplasma. The
      entire predicted structural gene encoded an antigenic protein composed of 172
      amino acids with a computed molecular mass of 19.15 kDa and a pl value of 9.78.
      The -10 region of the promoter and the terminator region of the gene were
      identified and found to be similar to those of prokaryotes. The hydropathy
      profile of the deduced amino acid sequence consisted of two distinct regions, a
      strongly hydrophobic N-terminus and a highly hydrophilic C-terminus. This major
      antigenic protein was also present in phytoplasma associated with peanut witches'
      broom (PNWB) and the two showed homology based on the results of Western blot
      analysis, Southern hybridization, Northern hybridization, primer extension
      analysis and PCR. The homologous genes of the antigenic protein of SPWB
      phytoplasma and PNWB phytoplasma were not found in other phytoplasmas tested.

PMID- 9611801
TI  - Characterization of plasmid pAW63, a second self-transmissible plasmid in
      Bacillus thuringiensis subsp. kurstaki HD73.
AB  - Bacillus thuringiensis subspecies kurstaki HD73, toxic for lepidopteran larvae,
      contains two large self-transmissible plasmids of approximately 75 kb, pHT73 and
      pAW63. The conjugative plasmid pHT73 has been studied extensively and has been
      shown to harbour the toxin gene cry1Ac, the transposon Tn4430 and several
      insertion sequences. In this study it was demonstrated that the minor plasmid
      pAW63 is also self-transmissible and about 10-30 times more efficient in
      mobilizing plasmid pBC16. To facilitate direct selection for pAW63 transfer, the
      plasmid was tagged with the tetracycline resistance transposon Tn5401 and in
      intraspecies matings it was found that after 2 h, all recipients had acquired a
      copy of the plasmid. Mating experiments demonstrated that pAW63 could be
      transferred to Bacillus thuringiensis subsp. israelensis, Bacillus cereus,
      Bacillus licheniformis, Bacillus subtilis and Bacillus sphaericus, and that the
      conjugative functions were expressed in these hosts. Hybridization studies showed
      that the replicons of pAW63 and pHT73 were distinct from one another. Sequences
      homologous to transposon Tn4430 and several insertion sequences were, however,
      shown to reside on both plasmids.

PMID- 9611802
TI  - The terminal structures of linear plasmids from Rhodococcus opacus.
AB  - The telomers of several linear plasmids of Rhodococcus opacus (formerly Nocardia
      opaca) were studied. The plasmids pHG201, pHG204 and pHG205 carry proteins bound
      to their ends, as shown by gel retardation experiments. A sequence hybridizing
      with the terminal sequence of pHG207, a recombinant linear plasmid consisting of
      the left part of pHG204 and the right part of pHG205, which was analysed in a
      previous study by the authors, could be detected in all linear plasmids of the
      wild-type R. opacus strains MR11 and MR22. However, only pHG204 and pHG206 carry
      terminal inverted repeats (TIRs) like pHG207. Cloning and sequencing of the
      terminal fragment of pHG204 revealed a nearly perfect TIR of 1016 bp. In
      contrast, the termini of pHG201 and pHG205 share little homology. Sequence
      analysis of the two end fragments of pHG201 revealed a similarity of only 65%
      within the terminal 34/32 bp and a perfect TIR of only 3 bp. The results support
      the assumption that long TIRs are not absolutely necessary for replication and
      maintenance of linear plasmids.

PMID- 9611803
TI  - Structural elements of the Streptomyces oriC region and their interactions with
      the DnaA protein.
AB  - Streptomycetes differ from other prokaryotic organisms in their mycelial life
      cycle and in possessing a large, linear, GC-rich chromosome. To deduce structural
      features of the Streptomyces origin of chromosomal replication, the oriC
      sequences of three Streptomyces species (S. antibioticus, S. chrysomallus and S.
      lividans) were compared. In Streptomyces, the oriC region contains 19 DnaA boxes
      whose location, orientation and spacing are conserved. The consensus sequence of
      the DnaA box identified within Streptomyces oriC is (T/C)(T/C)(G/A/C)TCCACA
      (preferred bases underlined). The interactions of DnaA with DNA fragments
      containing single, two or three DnaA boxes were studied using surface plasmon
      resonance. The dissociation constant (KD) for specific binding of individual DnaA
      boxes varied between 12 and 78 nM. Streptomyces oriC does not contain the three
      AT-rich 13-mer direct repeats present in the 5' part of the Escherichia coli oriC
      region. However, short AT-rich sequences are distributed among the DnaA boxes of
      Streptomyces oriC. Repeated attempts to unwind Streptomyces oriC have been
      unsuccessful. It remains to be elucidated whether DnaA interacts with putative
      accessory proteins which help in unwinding Streptomyces oriC.

PMID- 9611804
TI  - The Streptomyces reticuli alpha-chitin-binding protein CHB2 and its gene.
AB  - When co-cultivated with chitin-containing fungi, Streptomyces reticuli secretes
      the chitin-binding protein CHB2. Microscopical and immunological investigations
      revealed that CHB2 acts like a glue to mediate the contact between the fungal and
      the Streptomyces hyphae. CHB2 was purified to homogeneity, and the sequence of
      its N-terminal amino acids was determined and used to deduce an oligonucleotide,
      which was then used to probe a subgenomic library. The chb2 gene was cloned,
      sequenced and overexpressed. The deduced mature protein has a molecular mass of
      18.6 kDa, and a large number of its amino acids are identical to those of CHB1
      from Streptomyces olivaceoviridis. CHB2 effectively targets different types of
      alpha-chitin, but no other polysaccharide. The dissociation constant (Kd) for
      binding to purified crab shell chitin is 0.27 microM. Immunological studies
      suggest that homologues of CHB1 and CHB2 are secreted by streptomycetes while
      growing in the presence of alpha-chitin-containing substrates.

PMID- 9611805
TI  - A chitin-binding domain in a marine bacterial chitinase and other microbial
      chitinases: implications for the ecology and evolution of 1,4-beta-glycanases.
AB  - To examine the ecology and evolution of microbial chitinases, especially the
      chitin-binding domain, one of the chitinase genes (chiA) from the marine
      bacterium Vibrio harveyi was analysed. The deduced amino acid sequence of ChiA is
      not very similar overall to other proteins, except for two regions, the putative
      catalytic and chitin-binding domains. Among all bacterial chitinases sequenced to
      date, there is no relationship between percentage similarity of catalytic domains
      and chitin-binding domains in pairwise comparisons, suggesting that these two
      domains have evolved separately. The chitin-binding domain appears to be
      evolutionarily conserved among many bacterial chitinases and is also somewhat
      similar to cellulose-binding domains found in microbial cellulases and xylanases.
      To investigate the role of the chitin-binding domain, clones producing versions
      of ChiA with or without this domain were examined. One version with the domain
      (ChiA1) bound to and hydrolysed chitin, whereas a truncated ChiA without the
      putative chitin-binding domain (ChiA2) did not bind to chitin, but it could
      hydrolyse chitin, although not as well. ChiA1 diffused more slowly in agarose
      containing colloidal chitin than ChiA2, but diffusion of the two proteins in
      agarose without colloidal chitin was similar. These results indicate that the
      chitin-binding domain helps determine the movement of chitinase along N
      acetylglucosamine strands and within environments containing chitin.

PMID- 9611806
TI  - Fused nucleoids resegregate faster than cell elongation in Escherichia coli
      pbpB(Ts) filaments after release from chloramphenicol inhibition.
AB  - The course of nucleoid movement during and upon release from protein synthesis
      inhibition by chloramphenicol in filaments of Escherichia coli pbpB(Ts) was
      analysed. Cells were grown at 42 degrees C in glucose minimal medium for two mass
      doublings and were treated with chloramphenicol to generate fusion (coalescence)
      of the nucleoids. Upon release from protein synthesis inhibition, the large
      distance between the border of the fused nucleoids and the cell poles immediately
      decreased, before full recovery of the rates of mass growth and length increase
      at 30 degrees C. This indicates that nucleoids can reoccupy the DNA-free cell
      ends independently of cell elongation. During filamentation at 42 degrees C, the
      pbpB cells established initial constrictions at midcell and at one-quarter and
      three-quarter positions. Nevertheless, divisions only started 75 min after
      chloramphenicol removal at 30 degrees C, when most nucleoids had moved back into
      the vacated cell ends. No 'guillotine-like' constrictions at the site of the
      nucleoids occurred. This suggests that segregating nucleoids postpone division
      recovery at previously established sites. The results are discussed in the light
      of a working model for transcription/translation-mediated chromosome segregation
      and nucleoid occlusion of cell division.

PMID- 9611807
TI  - Environmentally controlled dimorphic cycle in a fission yeast.
AB  - The fission yeast Schizosaccharomyces pombe shows bipolar growth and is a
      convenient model for studying cell polarity and polar growth. This paper shows
      that the related Schiz. japonicus var. japonicus can switch to unipolar growth
      and can exist in both yeast and mycelial phases. On solid media, the yeast phase
      is unstable and prone to switch to the mycelial form, which shows unipolar growth
      by tip elongation. The hyphae can colonize the body of the substrate (true
      mycelium) or just its surface (pseudo-mycelium). The yeast-to-mycelium transition
      and the growth of the mycelium are regulated by a nutritional gradient and are
      associated with extensive vacuolation. The mycelium can convert into
      arthroconidia or return to the yeast phase in response to environmental changes.
      These environmentally controlled morphological transitions make Schiz. japonicus
      var. japonicus an attractive model for the investigation of cell polarity and
      morphogenesis.

PMID- 9611808
TI  - Structural characteristics of halobacterial gas vesicles.
AB  - Gas vesicle formation in halophilic archaea is encoded by a DNA region (the vac
      region) containing 14 different genes: gvpACNO and gvpDEFGHIJKLM. In
      Halobacterium salinarum PHH1 (which expresses the p-vac region from plasmid
      pHH1), gas vesicles are spindle shaped, whereas predominantly cylindrical gas
      vesicles are synthesized by the chromosomal c-vac region of H. salinarum PHH4 and
      the single chromosomal mc-vac region of Haloferax mediterranei. Homologous
      complementation of gvp gene clusters derived from the chromosomal c-vac region
      led to cylindrical gas vesicles in transformants and proved that the activity of
      the c-gvpA promoter depended on a gene product from the c-gvpE-M DNA region.
      Heterologous complementation experiments with transcription units of different
      vac regions demonstrated that the formation of chimeric gas vesicles was
      possible. Comparison of micrographs of wild-type and chimeric gas vesicles
      indicated that the shape was not exclusively determined by GvpA, the major
      structural protein of the gas vesicle wall. More likely, a dynamic equilibrium of
      several gvp gene products was responsible for determination of the shape.
      Transmission electron microscopy of frozen hydrated, wild-type gas vesicles
      showed moire patterns due to the superposition of the front and back parts of the
      ribbed gas vesicle envelope. Comparison of projections of model helices with the
      moire pattern seen on the cylindrical part of the gas vesicles provided evidence
      that the ribs formed a helix of low pitch and not a stack of hoops.

PMID- 9611809
TI  - Sequence and structural relationships of leucocins A-, B- and C-TA33a from
      Leuconostoc mesenteroides TA33a.
AB  - Amino acid sequences of two of the three bacteriocins from Leuconostoc
      mesenteroides TA33a were determined and their sequence-structure relationships
      investigated. Leucocin B-TA33a consists of 31 amino acid residues, with a
      molecular mass of 3466 Da. Leucocin B-TA33a does not belong to the pediocin
      family of bacteriocins, but shares 62% homology with mesenterocin 52B. A partial
      sequence of 36 amino acids of leucocin C-TA33a (4598 Da) was determined. Leucocin
      C-TA33a belongs to the class II bacteriocins having the consensus YGNGV motif.
      The third bacteriocin, leucocin A-TA33a, is identical to leucocin A-UAL 187.
      Circular dichroism spectra of the leucocins in aqueous solution and micellar SDS
      indicated that they undergo a structural transition when in a membrane-mimicking
      environment. Theoretical predictions from circular dichroism data suggest that
      leucocins A-, B- and C-TA33a adopt a beta-structure (48%) in membrane-mimicking
      environments. Sequence alignments and secondary structure predictions for the N
      terminus of leucocins A- and C-TA33a predicted that Cys-9 and Cys-14 are
      connected by a disulfide bridge and form two beta-strands.

PMID- 9611810
TI  - Molecular characterization of an autolytic amidase of Listeria monocytogenes EGD.
AB  - The gene encoding a 102 kDa autolysin has been cloned from an expression library
      of Listeria monocytogenes EGD genomic DNA, using a direct screening protocol. The
      encoded protein has two domains, an N-terminal enzymic domain showing a high
      level of homology to the amidase domain of the major autolysin (atl) of
      Staphylococcus aureus, and a C-terminal, putative cell-wall-binding domain
      containing four imperfect direct repeats. In order to examine the role of the
      enzyme, the autolysin-encoding gene was insertionally inactivated by site
      specific integration of a temperature sensitive plasmid. The enzyme accounts for
      66% of the total lytic enzyme activity when L. monocytogenes walls are used as
      substrate and several of the major autolytic bands are missing on renaturing gels
      when compared to the wild-type. The enzyme does not appear to be directly
      involved in cell separation but has a role in motility. Characterization of the
      recombinant enzyme expressed in Escherichia coli has revealed it to be an amidase
      and to be able to hydrolyse a range of peptidoglycan substrates.

PMID- 9611811
TI  - Structure of asparagine-linked oligosaccharides of an aspartic proteinase from
      the zygomycete fungus Rhizomucor pusillus.
AB  - The zygomycete fungus Rhizomucor pusillus (previously called Mucor pusillus)
      secretes an aspartic proteinase containing two asparagine-linked, high-mannose
      type oligosaccharide chains at Asn79 and Asn188. For structural elucidation of
      the carbohydrate moieties, the protein was divided into two portions, an N
      terminal portion containing Asn79 and a C-terminal portion containing Asn188, by
      a specific autocatalytic cleavage under alkaline conditions. Each of the
      asparagine-linked oligosaccharides was then released by peptide-N-glycosidase F
      digestion and pyridylaminated with a fluorescent reagent, 2-aminopyridine, at the
      reducing end. High-performance liquid chromatography analyses showed that the
      structure of the asparagine-linked oligosaccharide chain attached to residue
      Asn79 was Man5GlcNAc2, and that bound to residue Asn188 was Man5GlcNAc2 and
      Man6GlcNAc2. These observations suggest that the processing of mannose residues
      in asparagine-linked oligosaccharides in the Golgi apparatus of Rhizomucor
      resembles that in mammalian cells.

PMID- 9611812
TI  - Regulation of the sulfate starvation response in Pseudomonas aeruginosa: role of
      cysteine biosynthetic intermediates.
AB  - Pseudomonas aeruginosa PAO1 grew in defined synthetic medium with any of a broad
      variety of single sulfur sources, including sulfate, cysteine, thiocyanate,
      alkanesulfonates, organosulfate esters and methionine, but not with aromatic
      sulfonates, thiophenols or organothiocyanates or isothiocyanates. During growth
      with any of these compounds except sulfate, cysteine or thiocyanate, a set of 10
      sulfate starvation-induced (SSI) proteins was strongly up-regulated, as observed
      by two-dimensional protein electrophoresis of total cell extracts. A comparable
      level of up-regulation was found for the hydrolytic enzyme arylsulfatase, which
      has previously been used as a marker enzyme for the sulfate starvation response.
      One of the SSI proteins was identified by N-terminal sequencing as a high
      affinity periplasmic sulfate-binding protein, and another was related to thiol
      specific antioxidants, but the N-terminal sequences of the other SSI proteins
      revealed no similarity to N-termini of proteins of known function, and they
      probably represent uncharacterized enzymes involved in sulfur scavenging when
      preferred sulfur sources are absent. To study the role that cysteine biosynthetic
      intermediates play in the synthesis of these proteins in vivo, we isolated mini
      Tn5 transposon mutants of P. aeruginosa with insertions in the cysN and cysI
      genes, which encode subunits of ATP-sulfurylase and sulfite reductase,
      respectively. These two genes were cloned and sequenced. cysI showed high
      similarity to the cognate gene in Escherichia coli, whereas cysN encoded a 69.3
      kDa protein with two domains corresponding to the E. coli CysN and CysC proteins.
      Sulfate no longer repressed synthesis of the SSI proteins in cysN mutants, but
      repression was restored by sulfite; in the cysI mutant, sulfate, sulfite and
      sulfide all led to repression of SSI protein synthesis. This suggests that there
      are at least two independent corepressors of the sulfate starvation response in
      this species.

PMID- 9611813
TI  - Implications of the xylQ gene of TOL plasmid pWW102 for the evolution of aromatic
      catabolic pathways.
AB  - Pseudomonas putida strain O2C2 is able to grow on toluene, m-xylene and p-xylene
      through benzoate and the corresponding methylbenzoates (toluates). The catabolic
      genes are encoded on a large TOL plasmid, pWW102, of > 220 kb. The complete
      catabolic genes were cloned on four large overlapping restriction fragments
      covering a total of 28 kb of the plasmid, which was carefully mapped by
      restriction enzyme analysis. The presence of the xyl genes on the cloned DNA was
      confirmed by assay of representative enzymes of both operons. Virtually all the
      genes were located on the cloned DNA by hybridization of Southern blots with gene
      specific probes from related pathways of other catabolic plasmids. Within the
      limitations of available restriction sites, the analysis showed that the genes
      are in two blocks. The major block carries the meta pathway operon
      xylXYZLTEGFJQKIH with the two regulatory genes xylSR immediately downstream. The
      upper pathway operon xylUWCMAB(N) is about 2-3 kb downstream of the regulatory
      genes and transcribed in the same direction as the meta pathway operon. Within
      each operon the gene order appears to be identical to that found in other TOL
      plasmids, but the relative location of the operons most closely resembles that
      found on plasmid pWW53, although there is no evidence of any xyl duplications on
      pWW102. The nucleotide sequence of the xylQ gene for the acetaldehyde
      dehydrogenase (acylating; ADA), together with the 3'-end of the upstream xylJ
      (for 2-oxopent-4-enoate hydratase) and the 5'-end of the downstream xylK (for 4
      hydroxy-2-oxovalerate aldolase), was determined. The xylQ gene was ligated into
      expression vector pTrc99a and high levels of XylQ protein were detected by enzyme
      assay and by SDS-PAGE. All three genes xylJQK showed a high degree of homology
      with genes encoding isofunctional proteins from other Pseudomonas meta pathways,
      the highest being with the naphthalene catabolic genes nahLOM from the plasmid of
      Pseudomonas sp. NCIB 9816. The implications of the sequence homologies to the
      evolution of these pathways are discussed.

PMID- 9611814
TI  - Metabolism of ferulic acid via vanillin using a novel CoA-dependent pathway in a
      newly-isolated strain of Pseudomonas fluorescens.
AB  - A soil bacterium, designated Pseudomonas fluorescens AN103, was isolated based on
      its ability to grow on ferulic acid as a sole source of carbon and energy. In
      addition, this strain was found to metabolize a number of related phenolic
      substrates which contained a hydroxyl group at the para position of the aromatic
      ring. During growth on ferulic acid, transient accumulation of vanillic acid and
      trace amounts of protocatechuic acid were detected in the culture medium. Washed
      cells grown on ferulic acid readily oxidized vanillin, vanillic acid and
      protocatechuic acid, the three putative intermediates of the metabolic pathway.
      The side-chain cleavage of ferulic acid to produce vanillin was demonstrated in
      vitro for the first time and this enzyme-catalysed reaction was shown to have an
      essential requirement for CoASH, ATP and MgCl2. This conversion involved a two
      step process involving a CoA ligase followed by the side-chain cleavage. The
      addition of NAD increased the oxidation of vanillin to vanillic acid and had an
      overall effect of increasing the rate of ferulic acid cleavage. The application
      of 13C-NMR studies in vitro revealed acetyl-CoA as the C2 side-chain cleavage
      product. High levels of inducible ferulate-CoA ligase and NAD-linked vanillin
      dehydrogenase were detected and a novel pathway for ferulic acid metabolism in
      this organism is proposed.

PMID- 9611815
TI  - Spacing and orientation requirements of GcvA-binding sites 3 and 2 and the Lrp
      binding region for gcvT::lacZ expression in Escherichia coli.
AB  - Both GcvA and Lrp are required for normal regulation of the gcv operon. Moving
      the GcvA-binding sites 3 and 2 and the Lrp-binding region either closer to, or
      further away from, the gcv promoter by approximately one helical turn of DNA
      resulted in a less than twofold decrease in glycine-mediated activation or
      inosine-mediated repression of a gcvT::IacZ fusion. Moving these sites
      approximately two helical turns of DNA away from the gcv promoter resulted in a
      further loss of both activation and repression; moving these sites approximately
      three helical turns of DNA from the gcv promoter resulted in an essentially
      complete loss of both glycine-mediated activation and inosine-mediated
      repression. However, when these sites were moved by approximately 1.5 and 2.5
      helical turns of DNA away from the gcv promoter, there was a complete loss of
      both glycine-mediated activation and inosine-mediated repression of the
      gcvT::IacZ fusion. The flexibility in the absolute distance of the GcvA- and Lrp
      binding sites relative to the gcv promoter, but strict orientation dependence of
      these sites is consistent with a possible protein-protein interaction of either
      GcvA, Lrp, or both of these proteins with RNA polymerase. Because of the location
      of these target sites relative to the gcv promoter, it is also likely that DNA
      looping is required for this mechanism of regulation.

PMID- 9611817
TI  - Aspartate carbamoyltransferase from a psychrophilic deep-sea bacterium, Vibrio
      strain 2693: properties of the enzyme, genetic organization and synthesis in
      Escherichia coli.
AB  - The aspartate carbamoyltransferase (ATCase) genes of psychrophilic Vibrio strain
      2693 were cloned by complementation in Escherichia coli and the enzyme was partly
      characterized. The genes constitute a pyrBI operon homologous to the cognate
      structure in E. coli where pyrB and pyrI respectively encode the catalytic and
      the regulatory chains of ATCase. The strong sequence similarities noted between
      Vibrio and E. coli ATCases include extensive conservation of residues involved in
      interactions between subunits, suggesting that the two enzymes have very similar
      tertiary and quaternary structures. Vibrio ATCase is, however, not activated by
      ATP and not synergistically inhibited by CTP and UTP. It is also much more
      thermolabile than E. coli ATCase. With respect to Pyrococcus abyssi and E. coli
      ATCases, Vibrio ATCase presents marked differences in composition which could be
      related to its psychrophilic character. The results of these structural and
      functional comparisons indicate that Vibrio 2693 ATCase is a suitable model for
      biochemical studies on structure-function relationships in a 'cold' allosteric
      enzyme. The operon is expressed from a promoter which is immediately followed by
      a pyrimidine-rich leader ORF terminating within a putative transcription
      attenuator. These genetic and enzymic data strengthen the evolutionary
      relationship already noted between Vibrionaceae and Enterobacteriaceae.

PMID- 9611816
TI  - ppc, the gene for phosphoenolpyruvate carboxylase from an extremely thermophilic
      bacterium, Rhodothermus obamensis: cloning, sequencing and overexpression in
      Escherichia coli.
AB  - The ppc gene, which encodes phosphoenolpyruvate carboxylase (PEPC) of an
      extremely thermophilic bacterium, Rhodothermus obamensis, was directly sequenced
      by the thermal asymmetric interlaced (TAIL) PCR method. An ORF for a 937 amino
      acid polypeptide was found in the gene. The ppc gene had a high G+C content (66.2
      mol%) and the third position of the codon exhibited strong preference for G or C
      usage (85.0 mol%). The calculated molecular mass was 107,848 Da, which was
      consistent with the molecular mass of the enzyme as determined by SDS-PAGE (100
      kDa). The amino acid sequence of R. obamensis PEPC was closely related to that of
      PEPC from another thermophile, a Thermus sp., and from a mesophile,
      Corynebacterium glutamicum, exhibiting 45.3% or 37.7% identity and 61.5% or 56.5%
      similarity, respectively. By Southern analysis, the ppc gene was found to be
      present in a single copy in the genomic DNA of this organism. The cloned gene was
      expressed in Escherichia coli using a pET expression vector system and a
      thermostable recombinant PEPC was obtained. Comparison of the deduced amino acid
      sequences of the thermophilic and mesophilic PEPCs revealed distinct or common
      preferences for specific amino acid composition and substitutions in the two
      thermophilic enzymes.

PMID- 9611818
TI  - Comparison of PhoP binding to the tuaA promoter with PhoP binding to other Pho
      regulon promoters establishes a Bacillus subtilis Pho core binding site.
AB  - The phosphate-deficiency response in Bacillus subtilis is regulated by PhoP and
      PhoR, a pair of two-component regulatory proteins. PhoR is a histidine kinase and
      PhoP is a response regulator. Genetic evidence indicates that the Pho-regulon
      genes, which are induced or repressed under phosphate starvation conditions, are
      regulated by PhoP and PhoR at the transcriptional level. It has previously been
      shown that PhoP binds to four Pho-regulon promoters in both unphosphorylated and
      phosphorylated forms. This study demonstrates that another Pho-regulon gene
      promoter, the tuaA promoter preceding the operon which is responsible for cell
      wall teichuronic acid synthesis, is also transcriptionally regulated and is bound
      by PhoP. The binding affinity for phosphorylated PhoP was about 10-fold higher
      than that for unphosphorylated PhoP. Both unphosphorylated and phosphorylated
      PhoP bound upstream of the -20 region in the tuaA promoter. By aligning the PhoP
      binding sites within the Pho-regulon promoters, a consensus core PhoP-binding
      region composed of four TT(A/T)ACA direct repeats, each separated by 5 +/- 2 non
      conserved nucleotides was identified. PhoP, phosphorylated or unphosphorylated,
      binds to such a sequence in all Pho-regulon promoters studied. Phosphorylated
      PhoP binds to the core binding region with high affinity and to additional
      regions surrounding this region with similar or lower affinity.

PMID- 9611821
TI  - Managing genetic material to protect intellectual property rights.
AB  - One of the most important policy instruments for the promotion of further
      biotechnology development is intellectual property right (IPR) protection.
      However, one cannot improve upon a biotechnological invention without physical
      access to the germplasm, making exchanges of genetic material necessary. A formal
      transfer agreement, which addresses the key issues of ownership, access, use, and
      equitable benefit-sharing, is a powerful legal instrument for intellectual
      property. Other restrictions are generally imposed as a result of national and
      international safety regulations. Forming strategic alliances, such as joint
      ventures, collaborative research agreements, joint research and development
      agreements, and manufacturing and distribution alliances to exploit the economic
      value of genetic material, provides scientists with the mechanisms they need to
      bring their research material and products to the marketplace.

PMID- 9611819
TI  - Repression of nitrogen catabolic genes by ammonia and glutamine in nitrogen
      limited continuous cultures of Saccharomyces cerevisiae.
AB  - Growth of Saccharomyces cerevisiae on ammonia and glutamine decreases the
      expression of many nitrogen catabolic genes to low levels. To discriminate
      between ammonia- and glutamine-driven repression of GAP1, PUT4, GDH1 and GLN1, a
      gln1-37 mutant was used. This mutant is not able to convert ammonia into
      glutamine. Glutamine-limited continuous cultures were used to completely
      derepress the expression of GAP1, PUT4, GDH1 and GLN1. Following an ammonia
      pulse, the expression of GAP1, PUT4 and GDH1 decreased while the intracellular
      glutamine concentration remained constant, both in the cytoplasm and in the
      vacuole. Therefore, it was concluded that ammonia causes gene repression
      independent of the intracellular glutamine concentration. The expression of GLN1
      was not decreased by an ammonia pulse but solely by a glutamine pulse. Analysis
      of the mRNA levels of ILV5 and HIS4 showed that the response of the two
      biosynthetic genes, GDH1 and GLN1, to ammonia and glutamine in the wild-type and
      gln1-37 was not due to changes in general transcription of biosynthetic genes.
      Ure2p has been shown to be an essential element for nitrogen-regulated gene
      expression. Deletion of URE2 in the gln1-37 background prevented repression of
      gene expression by ammonia, showing that the ammonia-induced repression is not
      caused by a general stress response but represents a specific signal for nitrogen
      catabolite regulation.

PMID- 9611822
TI  - Isolation and characterization of ethanol-tolerant mutants of Escherichia coli
      KO11 for fuel ethanol production.
AB  - Genetically engineered Escherichia coli KO11 is capable of efficiently producing
      ethanol from all sugar constituents of lignocellulose but lacks the high ethanol
      tolerance of yeasts currently used for commercial starch-based ethanol processes.
      Using an enrichment method which selects alternatively for ethanol tolerance
      during growth in broth and for ethanol production on solid medium, mutants of
      KO11 with increased ethanol tolerance were isolated which can produce more than
      60 g ethanol L-1 from xylose in 72 h. Ethanol concentrations and yields achieved
      by the LY01 mutant with xylose exceed those reported for recombinant strains of
      Saccharomyces and Zymomonas mobilis, both of which have a high native ethanol
      tolerance.

PMID- 9611823
TI  - Isolation and partial characterization of a lectin from Artocarpus incisa L.
      seeds.
AB  - A lectin was isolated from the saline extract of Artocarpus incisa seed by
      affinity chromatography on cross-linked Adenanthera pavonina galactomannan in
      0.15 M NaCl. The lectin was also retained in a D-gal-agarose resin and had no
      requirements for divalent metal cations (Ca2+ and Mn2+) for activity. The lectin
      contains 2.1% of carbohydrate and is characterized by high contents of acidic and
      hydroxylated amino acids. The lectin presented two protein bands in SDS-PAGE,
      with M(r) 15.5 and 12 kDa, respectively, and contains no alpha-helix, 64%
      antiparallel beta-sheet and 21% parallel beta-sheet/beta-turn. When submitted to
      gel filtration in Superose 12 R (FPLC) and Superdex 75 HR 5/5 (HPLC) columns, the
      lectin showed an M(r) of 48-49 kDa, suggesting a tetrameric structure.

PMID- 9611824
TI  - Gum heteropolysaccharide and free reducing mono- and oligosaccharides of
      Anadenanthera colubrina.
AB  - The gum from Anadenanthera colubrina consists mainly of a complex high-arabinose
      heteropolysaccharide with a (1-->3)-linked beta-D-Galp main-chain and many
      different side-chains. These contain beta-D-Galp-[(1-->6)-beta-D-Galp]m-(1-->6)-,
      substituted in turn at O-3 by alpha-L-Araf-[(1-->3)-alpha-L-Araf-]0-2. Also
      present are (1) main-chain units substituted at O-4 and O-6 by alpha-L-Araf
      units, (2) side-chains of Rhap-(1-->4)-beta-D-GlcpA-(1-->6)-beta-Galp-groups, (3)
      alpha-L-Arap non-reducing end-units linked (1-->6) to D-Galp, and (4) beta-Araf
      and beta-Arap structures. For the first time, a plant gum exudate was found to
      contain in the natural state, reducing low M(r) carbohydrates. These were
      rhamnose (0.6%), arabinose (4.7%), mannose (0.1%), galactose (0.8%) and many
      oligosaccharides (0.6%; 11 with different RFs, with the majority containing
      arabinose). They were all mixtures with the exception of alpha-Rhap-(1-->4)-beta
      D-GlcpA-(1-->6)-alpha beta-Gal and an incompletely identified hexasaccharide,
      probably having alpha-L-Araf-(1-->4)-beta-D-Galp- and -alpha-L-Araf-(1-->3)-beta
      D-Galp- structures. The mono- and oligosaccharides do not appear to arise via in
      situ autohydrolysis of the gum.

PMID- 9611825
TI  - Inhibition in vitro linoleic acid peroxidation and haemolysis by
      caffeoyltryptophan.
AB  - Antioxidant activities of caffeoyltryptophan were investigated by the 1,1
      diphenyl-2-picrylhydrazyl (DPPH) radical scavenging system, the superoxide anion
      generation system and the superoxide anion-mediated linoleic acid peroxidation
      system. At 10 microM, caffeoyltryptophan showed greater scavenging activity on
      DPPH than dl-alpha-tocopherol or ascorbic acid. DPPH radical scavenging activity
      of caffeoyltryptophan increased dose-dependently at concentrations ranging from 1
      to 50 microM; 1 mol of caffeoyltryptophan reacted with ca 4 mol of radical.
      Caffeoyltryptophan caused 80% inhibition of superoxide anion generation at 50
      microM. The inhibitory activity of caffeoyltryptophan was as strong as that of 5
      caffeoylquinic acid. Caffeoyltryptophan inhibited the formation of conjugated
      diene from linoleic acid. The inhibitory activity increased in the order caffeic
      acid < 5-caffeoylquinic acid < caffeoyltryptophan < dl-alpha-tocopherol. Effects
      on the in vitro haemolysis and peroxidation of mouse erythrocytes induced by H2O2
      were also examined. Caffeoyltryptophan exhibited strong inhibitory activities;
      Tryptophan was ineffective in these systems. These data suggest that
      caffeoyltryptophan may be a natural antioxidant in the human diet and, as such,
      may intervene in toxicological processes that are mediated by radical mechanisms.

PMID- 9611826
TI  - Secoiridoid glycosides and an antifungal anthranilate derivative from Gentiana
      tibetica.
AB  - Repetitive chromatography of the methanol extract of the roots of Gentiana
      tibetica afforded two new secoiridoid glycosides and a novel antifungal
      anthranilic acid derivative, together with beta-sitosterol, daucosterol,
      oleanolic acid, loganic acid, gentiopicroside, sweroside, 2'-(2,3
      dihydroxybenzoyl)sweroside, trifloroside, rindoside and macrophylloside A. The
      structures of the new products were determined mainly by spectroscopic methods as
      8-hydroxy-10-hydrosweroside, isomacrophylloside and ethyl N
      docosanoylanthranilate. Ethyl N-docosanoylanthranilate inhibited the growth of
      the human pathogenic fungi Candida albicans and Aspergillus flavus. The taxonomic
      significance of the constituent is discussed briefly.

PMID- 9611827
TI  - Biotransformation of digitoxigenin by cultured Strophanthus hybrid cells.
AB  - Hybrid cells between Strophanthus gratus and S. amboensis were obtained by
      electrofusion and confirmed to be hybrids through isozyme and RFLP analyses.
      Because a new and hybrid compound, 17 beta H-periplogenin beta-D-glucoside, was
      isolated as a biotransformation product of digitoxigenin by the hybrid cells,
      isomerization of 17 beta-lactone ring on S. gratus and glucosylation on S.
      amboensis were demonstrated simultaneously as the biotransformation abilities in
      the hybrid cells. Moreover, the productivity of the hybrid compound was increased
      by raising the sucrose concentration.

PMID- 9611828
TI  - Limonoids from Azadirachta excelsa.
AB  - Activity-directed fractionation of a stem extract of Azadirachta excelsa using KB
      (human oral epidermoid carcinoma) cells led to the isolation of four meliacin
      type limonoids. Two of these constituents were novel, namely, 2,3
      dihydronimbolide and 3-deoxymethylnimbidate, and these were purified along with
      the known compounds, nimbolide and 28-deoxonimbolide. The structures of the new
      compounds were determined by spectroscopic methods. Nimbolide and 28
      deoxonimbolide were broadly cytotoxic when evaluated against a panel of human
      cancer cell lines, while the two novel compounds were inactive in this regard.
      The defection of nimbolide and 28-deoxonimbolide as cytotoxic constituents was
      facilitated by an electrospray LC/MS dereplication procedure.

PMID- 9611829
TI  - Triterpenoid saponins from Vaccaria segetalis.
AB  - Four novel triterpenoid saponins were isolated from the seeds of Vaccaria
      segetalis. Their structures were established as vaccaroside A, gypsogenic acid-28
      O-beta-D- glucopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->6)-[beta-D-
      glucopyranosyl-(1-->3)]-beta-D-glucopyranoside; vaccaroside B, gypsogenic acid-28
      O-beta-D-glucopyranosyl-(1-->2)-[3-hydroxyl-3- methylglutaroyl-(1-->6)]-beta-D
      glucopyranosyl-(1-->6)-[beta-D- glucopyranosyl-(1-->3)]-beta-D-glucopyranoside;
      vaccaroside C, 23-O-beta-D-glucopyranosyl-gypsogenic acid-28-O-beta-D-
      glucopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->6)- [beta-D-glucopyranosyl-(1-
      >3)]-beta-D-glucopyranoside and vaccaroside D, 3,4-secogypsogenic acid-28-O-beta
      D-glucopyranosyl-(1-->3)- [beta-D-glucopyranosyl-(1-->6)]-beta-D-glucopyranoside
      by a combination of extensive NMR (DEPT, COSY, HOHAHA, HETCOR, HMBC and NOESY)
      studies and chemical degradation.

PMID- 9611830
TI  - Styryl-pyrones from Goniothalamus arvensis.
AB  - Two novel styrl-pyrones, (+)-garvensintriol and (+)-etharvendiol, together with a
      known cytotoxic furano-furone, (+)-goniofufurone, have been isolated from the
      stem bark of Goniothalamus arvensis. A different relative configuration, cis
      erythro-erythro for garvensintriol and cis-threo-erythro for etharvendiol, is
      established, and their absolute stereochemistry is discussed.

PMID- 9611831
TI  - Flavonol glycosides from Dasymaschalon sootepense.
AB  - Two novel flavonol glycosides have been isolated from a methanolic extract of
      Dasymaschalon sootepense leaves. They are the 3'-neohesperidoside and 3'(6G-alpha
      rhamnosylneohesperidoside) of quercetin 3,7-dimethyl ether.

PMID- 9611832
TI  - A new class of wine pigments generated by reaction between pyruvic acid and grape
      anthocyanins.
AB  - A new class of stable red pigments detected in grape pomace was analysed by
      electrospray ionisation mass spectrometry. They were shown to be pyruvic acid
      derivatives of genuine grape anthocyanins by synthesis experiments. The major
      product was identified by NMR (1H, NOE, HSQC, HMBC) experiments as the malvidin-3
      monoglucoside pyruvic acid adduct. Its formation results from cyclisation between
      C-4 and the hydroxyl group at C-5 of the original flavylium moiety with the
      double bond of the enolic form of pyruvic acid, followed by dehydration and
      rearomatisation steps. This type of reaction leads to increased colour stability.
      Various yeast metabolites other than pyruvic acid were shown to react with grape
      anthocyanins following this mechanism, suggesting that it may be an important
      route of conversion into stable pigments during the maturation and ageing of
      wine.

PMID- 9611833
TI  - The ombudsman's contribution to quality.

PMID- 9611834
TI  - Defining and achieving quality of medical care.

PMID- 9611835
TI  - A comparison of ambulatory Medicaid claims to medical records: a reliability
      assessment.
AB  - This study compares the documentation of ambulatory care visits and diagnoses in
      Medicaid paid claims and in medical records. Data were obtained from Maryland
      Medicaid's 1988 paid claims files for 2407 individuals who were continuously
      enrolled for the fiscal year, had at least one billed visit for one of six
      indicator conditions, and had received the majority of their care from one
      provider. The patients sampled were also stratified on the basis of the case-mix
      adjusted cost of their usual source of care. The medical records for these
      individuals as maintained by their usual source of care were abstracted by
      trained nurse reviewers to compare claims and record information. Linked claim
      and medical record data for sampled patients were used to calculate: (i) the
      percent of billed visits documented in the record, (ii) the percent of medical
      record visits where both the date and the diagnosis agreed with the claims data,
      and (iii) the ratio of medical record visits to visits from billed claims.
      Included in the analysis were independent variables specifying place of
      residence, type and costliness of usual care source, level of patient
      utilization, and indicator condition on which patient was sampled. Ninety percent
      of the visits chronicled in the paid claims were documented in the medical record
      with 82% agreeing on both date and diagnosis. Compared to the medical records
      kept by private physicians and community health centers, a significantly lower
      percent of hospital medical records agreed with the claims data. Total volume of
      visits was 2.6% higher in the medical records than in the claims. Claims data
      substantially understated visits in the medical record by 25% for low cost
      providers and by 41% for patients with low use rates (based on claims
      information). Conversely, medical records substantially understated billed visits
      by 19% for rural patients and by 10% for persons with high visit rates. Although
      Medicaid claims are relatively accurate and useful for examining average
      ambulatory use patterns, they are subject to significant biases when comparing
      subgroups of providers classified by case-mix adjusted cost and patients
      classified by utilization rates. Medicaid programs are using claims data for
      profiling and performance assessment need to understand the limitations of
      administrative data.

PMID- 9611836
TI  - A comparative study of the psychiatric care between locum tenens and staff
      physicians in a state hospital.
AB  - Artificial neural networks (ANNs) were used to measure the quality of care (Q) at
      two admission units in a state psychiatric hospital, each unit having two
      treatment teams, one led by a permanent (PM) staff physician, and one led by
      various locum tenens (LT) physicians. An LT physician's tour of duty (TOD)
      averaged approximately 30 days. Over nearly a 2 1/2-year period the four
      treatment teams received 744 admissions. Our previous research has reported
      measuring Q using percent accurate prediction of hospital length-of-stay (LOS),
      divided by a measure of severity of patient illness. We calculated Q for each
      treatment team's test set of patients using a trained ANN for each team. All the
      teams' test sets were run through each of the trained ANNs resulting in a set of
      four Q values for each ANN. We defined the standard deviation of Qs resulting
      from a single team's test set run through it own as well as the other three
      teams' ANNs as representative of the "diversity" of the patients in that test
      set. We defined the reciprocal of the standard deviation of the Qs resulting from
      each of the teams' test sets run through a single team's ANN as that team's
      "robustness." The product of "robustness" times "diversity" was defined as the
      value (V) of the treatment team. The V of the PM physician-led teams was 1.9
      times that of the LT physician-led teams. We normalized V for patient entropy
      (uncertainty) with a metric called the "risk ratio" (RR), derived from
      Boltzmann's law. This resulted in the V/RR of one PM physician-led team as
      superior, despite treating patients with the highest risk. The LT physician-led
      teams, despite having fewer patients afflicted with the more problematic
      diagnosis of schizophrenia, were handicapped by not having preexisting
      therapeutic relationships with their patients, giving both LT teams low
      robustness. There was no statistically significant difference in patient LOS
      between the teams. Because the greatest change in team composition was due to LT
      physicians, we assumed that the differences in V/RR were due to the short (30
      day) TOD and not to any skill deficits in the LT physicians. This article
      explores a new paradigm which compares the value of patient care in separate
      delivery systems despite differences in severity of illness, case-mix, and
      uncertainty associated with an imperfect therapeutic environment.

PMID- 9611837
TI  - Utilization review of simultaneously ordered multiple radiologic tests for the
      same symptom.
AB  - The purpose of this study was to analyze the utilization of multiple radiologic
      procedures ordered simultaneously for the same clinical problem. The method was a
      retrospective study of patients referred to an urban community hospital who had
      multiple radiologic tests ordered simultaneously before the referring physician
      reviewed any of the results. Utilization Findings Codes, beta versions II and
      III, of the American College of Radiology were applied. In- and outpatient charts
      were reviewed for initial indication, subsequent diagnosis, and treatment. Ninety
      three patients had 214 radiologic examinations (2.3 per patient). Of the 214
      total, 129 (60%) were retrospectively coded as inappropriate (beta II version).
      For 98 reports, the initial interpreting radiologist's coded 16% as inappropriate
      versus 55% when retrospectively coded by the authors (P < 0.0001). After applying
      the beta III version, 18% were coded as positive (and related to symptoms), 79%
      negative, and 3% equivocal. There were 161 (74%) examinations ordered by primary
      care physicians and 53 tests ordered by specialists. Using the beta III version,
      the negative rate for primary care physicians was 81 and 75% for specialists (P =
      0.447). It was concluded that ordering multiple radiologic tests simultaneously
      on the same patient resulted in a high number of inappropriate procedures and
      negative results.

PMID- 9611838
TI  - Centralization of histocompatibility laboratories: impact on organ allocation
      efficiency and outcomes of cadaveric renal transplantation.
AB  - This project was undertaken to determine whether centralization of
      histocompatibility laboratory services for renal transplants performed within
      eastern Pennsylvania could improve the efficiency of allograft allocation and
      short-term allograft function. A nonconcurrent cohort study was performed
      comparing renal allografts transplanted between September 15, 1993, and September
      14, 1994, to those transplanted between September 15, 1994, and September 14,
      1995. All allografts were procured and allocated by the Delaware Valley
      Transplant Program, the organ procurement agency in eastern Pennsylvania. Cold
      preservation time and delayed allograft function were used to measure efficiency
      of allograft allocation and short term allograft function, respectively. The mean
      cold preservation time was reduced from 25.08 hours to 20.68 hours (P < 0.001).
      The percentage of delayed allograft function was 19.9 and 17.4 for the pre- and
      postcentralization groups, respectively (P = 0.5). Therefore, centralization of
      histocompatibility tissue typing was a regionally effective process intervention
      for reducing cold preservation time without adversely impacting short-term graft
      function. The magnitude of this reduction varied between individual centers.
      Further investigation is required to determine the effect on long-term allograft
      function and system wide costs.

PMID- 9611839
TI  - Problems in assessing diabetes control in an ambulatory setting.
AB  - Problems in using medical records to assess outcomes of diabetes care have not
      been well defined. We reviewed the medical records of 288 patients with diabetes
      receiving ambulatory care over a 2-year period. We determined the availability of
      different tests of glycemic control and described site performance as the
      percentage of patients with a blood glucose exceeding either 180 or 240 mg/dl.
      Glycosylated hemoglobin determinations were performed in only 26.7% of patients.
      A blood glucose was available in 208 patients (72.2%) during a 6-month outcome
      period. For almost 50% of the sample, the glucose was greater than 180 mg/dl,
      whereas in 20% it exceeded 240 mg/dl. Judgments of whether sites differed in
      performance depended on how control was defined. Using a single glucose
      determination and a threshold of 180 mg/dl, similar fractions of patients were
      poorly controlled at each site (51.2 versus 45.0 versus 47.0%) (P = 0.75). At 240
      mg/dl, although, one site performed much worse than the other two (14.6 versus
      16.7 versus 31.8%) (P = 0.02). These results highlight difficulties in defining
      the outcome measure when using medical records to evaluate quality of care.

PMID- 9611840
TI  - Are preoperative antibiotics administered preoperatively?
AB  - Ideally antibiotics should be administered preoperatively within 2 hours of skin
      incision to ensure adequate tissue concentrations, especially when a vascular
      prosthesis is used. The quality of patient outcomes may be adversely affected
      when key processes, by degrees, fail to meet patient care objectives. This study
      was designed to incorporate the concepts of total quality management to determine
      how effectively this goal was achieved, and, after review of those measured
      results, what process improvements could be instituted to meet the established
      requirements for the administration of antibiotics. The study was then repeated
      on a yearly basis to determine what effect these improvement measures had on
      antibiotic administration. Three time periods were established for determining
      when antibiotics were administered. The "early" period was more than 2 hr
      preoperatively. "Preoperative" was from 2 hr before surgery until the time of
      incision and "perioperative" was after the time of incision. Group 1 consisted of
      the first 100 patients undergoing vascular procedures in 1992. After the data
      were collected, a multidisciplinary team of nurses, pharmacists, and surgeons was
      assembled to determine the step by step desired process flow from order received
      to actual medication administration. The team then reviewed each step of the
      process to identify variations relative to data obtained. An action plan was
      developed to implement the agreed upon improvement plan. After improvements were
      implemented, groups 2, 3, 4, and 5 consisted of the first 100 vascular procedures
      of 1993, 1994, 1995, and 1996. Group 1 had only 26% of antibiotics administered
      during the preoperative period and 74% during the perioperative period. Problems
      identified were: surgeons ordered the antibiotics when the patient was in the
      operating room, cefamandole and vancomycin required at least 1 hr to infuse,
      nurses were not aware of the need for preoperative infusion, and the pharmacy did
      not supply the antibiotics in a timely fashion. Educational inservices were held
      for all parties involved, and cefazolin was used in place of cefamandole because
      it could be given as a bolus. Results were: group 1, early, 0%; preoperative,
      26%; perioperative, 74%; P = N/A; group 2, early, 0%, preoperative, 90%;
      perioperative, 10%; group 3, early, 7%; preoperative, 93%; perioperative, 0%;
      group 4, early 0%; preoperative, 100%; perioperative, 0%; and group 5, early, 0%;
      preoperative, 100%; perioperative, 0%; P = 0.0001 for groups 2-5 (versus group
      1). It was surprising how often antibiotics were administered incorrectly in a
      busy vascular practice. By focusing on the process of care delivery, a continuous
      quality improvement team implemented simple changes that resulted in significant
      improvements. We are now conducting a study to determine what effect these
      process improvements had on our infection rate.

PMID- 9611841
TI  - The impact of clinical guidelines on practice patterns: doing more versus doing
      less.
AB  - This study examined the determinants of compliance with clinical guidelines for
      glucocyte colony-stimulating factor (GCSF), a biotechnology product designed to
      reduce postchemotherapy infections. The pattern of compliance did change over
      time. After the guidelines were disseminated, appropriate use of GCSF increased.
      However, inappropriate use also increased. Patients who were younger and had an
      attending physician who was an oncologist or hematologist were more likely to
      receive GCSF whether they met the guideline criteria or not. Our findings suggest
      that older patients may be treated less aggressively than others and that
      physicians who are the most knowledgeable about guidelines may feel the most
      qualified to override the guidelines when they believe they do not apply. Our
      findings also demonstrate that it is easier to encourage physicians to do more
      for patients rather than less.

PMID- 9611842
TI  - Commentary: clinical decision support for quality management.

PMID- 9611843
TI  - New 4-thiazoline-2-hydrazono-1H-2-indolinones as possible antimicrobial agents.
AB  - In order to test their antimicrobial activity a series of new 3-[(3-substituted-4
      methyl-5-carboxy/carbetoxy-4-thiazolin-2 - ylidene)hydrazono]-1H-2-indolinones
      (3a-i/4) were synthesized from the reaction of 3-(4-substituted-3
      thiosemicarbazono-1H-2-indolinones (1a-I) with 2-chloroacetoacetic acid ethyl
      ester (2). All synthesized compounds were characterized by IR, 1H-NMR, EIMS and
      elementary analysis.

PMID- 9611844
TI  - [What model for pharmacokinetic analysis of tissue distribution and
      bioequivalence?].
AB  - Pharmacokinetic analysis of experimental data is usually carried out through two
      different approaches: non compartmental model or standard compartmental models.
      Benefits and restrictions of these two approaches are here discussed, with
      attention to the studies of clinical pharmacokinetics and, particularly, to those
      of bioavailability and bioequivalence. In fact, different opinions about the most
      appropriate model to be used with these studies were encountered. Besides, the
      paper deals with European and American guidelines, data from a check of the
      literature published during 1995 on two international journals of clinical
      pharmacology and results of non-compartmental and non-linear fitting analyses on
      plasma concentrations obtained with an oral administration of a delayed dosage
      form in humans.

PMID- 9611845
TI  - Preparation of targeted isoniazid microspheres.
AB  - Isoniazid (INH) albumin microspheres were prepared by two different stabilization
      processes: chemical denaturation using glutaraldehyde and heat denaturation. The
      extent of stabilization was characterized by the solubility of the microspheres.
      In vitro drug release rates were correlated to the stability of the microspheres
      and the results showed that the more denatured the albumin by heat stabilization,
      the slower the drug release rate. A factorial concept has been utilized to
      synthesize microspheres suitable for passive targeting to the lungs by varying
      protein concentration, stabilization temperature, time and aqueous volume. These
      factors significantly affected the sphere size, payload and a release profile of
      the drug. As the severity of the denaturation conditions increased, the payload
      decreased and the rate of drug release was slowed. The microspheres carrying
      isoniazid were followed in experimental animals to validate the targeting
      process.

PMID- 9611846
TI  - Synthesis and analgesic properties of new 5-thioaryl pyrazole derivatives.
AB  - A new series 5-thio aryl pyrazole derivatives were proposed aiming analgesic
      activity. In this work, 8 new compounds of this class were synthesized using
      usual synthetic methodology, having as key intermediate the 3-methyl-4-nitro-5
      chloropyrazole-1-phenyl derivative and subsequent reaction with several
      nucleophiles sulfides. Pharmacological evaluation of this series showed analgesic
      activity in the some extent in especially for 5-(4-bromophenyl)-thio-3-methyl-4
      nitro-1-phenylpyrazole which was the most potent in this series, presenting an
      analgesic action comparable to that show by dipyrone.

PMID- 9611847
TI  - Studies on arylmethyltriazinone derivatives-Part II. Synthesis and antifungal
      properties of 2-aminomethyl-4-(arylidene)amino-6-arylmethyl- 3-mercapto-1,2,4
      triazin-5(4H)-ones.
AB  - The preparation of twenty new 2-aminomethyl-4-(arylidene)amino- 6-arylmethyl-3
      mercapto-1,2,4-triazin-5(4H)-ones(4) is described. The structural elucidation of
      all the compounds is carried out on the basis of analytical and spectral data.
      The newly synthesized compounds are evaluated for their antifungal activity
      against Candida albicans and Paecileomyces variotti.

PMID- 9611848
TI  - [Ventricle and aorta: nostalgia of a happy relation].

PMID- 9611849
TI  - Basic training in cardiology: theory and reality.

PMID- 9611850
TI  - [Paradoxical embolism in patent foramen ovale].

PMID- 9611851
TI  - [Mineralocorticoids and hypertension].

PMID- 9611852
TI  - [Spinal cord protection in surgery of the descendent thoracic aorta].

PMID- 9611853
TI  - Diuretic therapy and angina pectoris.

PMID- 9611854
TI  - Plaque morphology in sudden coronary death.

PMID- 9611855
TI  - [Significance of electrocardiographic projection of ST-segment depression during
      exercise test in the prediction of the location of regional myocardial ischemia].
AB  - There is still some controversy whether ST segment depression during exercise
      testing might predict the location of myocardial ischemia. From a population of
      1196 patients who underwent myocardial 99mTc-tetrofosmin exercise SPECT
      scintigraphy, 22 consecutive patients (20 males and 2 females, mean age 54 +/- 10
      years) with no previous myocardial infarction, positive exercise testing (> or =
      1 mm ST segment depression) performed in pharmacologic wash-out and
      angiographically documented isolated single vessel coronary artery disease (> or
      = 70% diameter stenosis in a main coronary artery) were selected. None of the
      patients showed > or = 1 mm ST segment depression exclusively in inferior leads
      (II-III-aVF). Eight patients (36%) showed > or = 1 mm ST segment depression
      exclusively in precordial leads (Group 1). The remaining 14 patients (64%) showed
      > or = 1 mm ST segment depression in both inferior and precordial leads (Group
      2). No differences between groups were observed regarding peak exercise test
      parameters such as heart rate (124 +/- 28 vs 135 +/- 21 b/min, NS), rate-pressure
      product (22592 +/- 5323 vs 23118 +/- 4197 mmHg x b/min, NS) and exercise time
      (14.5 +/- 3.9 vs 15.1 +/- 2.9 min, NS) and the number of stress-induced
      reversible and partially reversible defects (3.3 +/- 3.4 vs 4.6 +/- 2.8, NS). All
      reversible and partially reversible defects were seen in the related coronary
      artery stenosis region. Among Group 1, 5 patient (62.5%) showed a > or = 70%
      stenosis of left descending coronary artery, 1 patient (12.5%) of left circumflex
      and 2 patients (25%) of right coronary artery. Similarly, among Group 2, 9
      patients (64.3%) showed a significant stenosis of left descending coronary
      artery, 1 patient (7.1%) of left circumflex and 4 patients (28.6%) of right
      coronary artery. Thus, we were not able to show a relation between exercise ST
      segment depression and the location of myocardial ischemia as assessed by
      myocardial 99mTc-tetrofosmin SPECT scintigraphy in a population of patients
      selected on the basis of single coronary artery disease.

PMID- 9611856
TI  - [Early detection of heart involvement using serial cardiologic controls in the
      follow-up of patients with AIDS].
AB  - New effective therapies have been producing longer survival times for HIV
      patients. Thus non-infectious complications of late stage of HIV infection (such
      as the development of left ventricular dysfunction) have emerged; in fact cardiac
      involvement has been identified frequently at autopsy and is described in 80% of
      patients with acquired immunodeficiency syndrome (AIDS) as an evidence of the
      virus cardiotrophism, while clinical findings of left ventricular dysfunction
      were only detected in about 15% of the patients. It is possible that the
      development of heart failure had been underestimated in those years; in fact
      signs and symptoms of cardiac involvement had been often misinterpreted as the
      results of non cardiac causes (pulmonary failure or infections) also determining
      a delay in the beginning of cardiac therapy. The aim of this study was to follow
      16 human immunodeficiency-virus positive patients during a 3-year period to
      evaluate the usefulness of early detection of heart failure in order to start a
      specific therapy as soon as possible. The follow-up consisted of a clinical and
      electrocardiographic control every 4 months. Echocardiography was carried out
      when involvement of the cardiac muscle was suspected. During the follow-up we
      could reveal an early involvement in 5/16 patients (31.2%) and in 2 of them (40%)
      early therapy caused clinical and echocardiographic regression of left
      ventricular dysfunction. The present study demonstrates that periodical clinical
      and echocardiographic controls are useful in patients with HIV infection.

PMID- 9611857
TI  - The influence of pacing rate and autonomic blockade on human primary and
      secondary atrial pacemakers.
AB  - The morphology of the first spontaneous post-pacing P wave was assessed in 106
      patients who underwent electrophysiological study for various arrhythmias. An
      overall number of 589 atrial pacing sessions, from 60-200 b/min, were analyzed
      (mean 5.55 +/- 1.3 session per patient). After cessation of 138 (23.42%) of them,
      spontaneous post-pacing P wave arose from extrasinus foci. Nonsinus spontaneous
      post-pacing P waves were recorded after 1 or more pacing rates (from 1 to 7) in
      58 patients (54.7%, Group 1). In the remaining 48 patients the spontaneous post
      pacing P waves were sinus after all pacing sessions (45.3%, Group 2). Sinus node
      disease (SND) was present in 32.7% of Group 1 patients and in 2% of Group 2 (p =
      0.002). Spontaneous post-pacing P wave of extrasinus origin was recorded in 19/20
      of SND patients (95%) compared to 39/86 of patients with normal sinus function
      (45.34%, p < 0.001). SND patients had a greater number of pacing sessions
      resulting in nonsinus spontaneous post-pacing P waves. Pacing rate associated
      with nonsinus spontaneous post-pacing P waves was lower in SND patients compared
      to patients with normal sinus node function. In the SND group, nonsinus
      spontaneous post-pacing P waves were recorded beyond the first spontaneous one in
      9 patients compared to only 1 in patients with normal sinus node function (p <
      0.005). Extrasinusal first spontaneous post-pacing P waves at a pacing rate of
      140 b/min had the highest sensitivity (75%). Increasing of pacing rate from 60 to
      140 b/min was associated with progressive arousal of secondary foci with highest
      value of 36.8% in pacing rate of 140 b/min. Further increase of pacing rate
      resulted in a slight reduction of spontaneous post-pacing firing from secondary
      foci. Atropine was administered in 12 Group 1 patients and abolished all
      measurable morphological changes of spontaneous post-pacing P waves compared to
      pre-pacing. Autonomic blockade was performed in 14 Group 1 patients and 16 Group
      2 patients. In 35.7% of Group 1 patients autonomic blockade abolished the
      appearance of nonsinus spontaneous post-pacing P waves, while in the remaining
      patients increased the lowest pacing rate resulting in nonsinus spontaneous post
      pacing P waves. In 12.5% Group 2 patients autonomic blockade resulted in nonsinus
      spontaneous post-pacing P waves after cessation of atrial pacing. In conclusion,
      the extrasinus spontaneous rise of atrial impulse is a very frequent phenomenon
      after atrial pacing especially in patients with SND. Pacing rate has different
      quantitative effects on sinus and secondary atrial pacemakers. Secondary
      pacemakers are less under autonomic control compared to sinus node.

PMID- 9611858
TI  - [Effects of cardiomegaly on the anatomical and functional state of the lung in
      chronic heart failure].
AB  - Heart and lungs might compete for the intrathoracic space in case of heart
      enlargement (as in heart failure). Therefore, the pulmonary abnormalities
      observed in patients with chronic heart failure (restrictive pattern and
      reduction of diffusion capacity) might be at least in part related to
      cardiomegaly. In 53 patients (11 women, 42 men, mean age 65 +/- 8 years) with
      stable heart failure and cardiac enlargement (cardiothoracic ratio-Ctr > or =
      50%) we measured carbon monoxide lung diffusion (DLCO), lung tissue content (VT,
      single breath, expiratory regression of acetylene), alveolar volume (Va, single
      breath, expiratory regression of methane) and vital capacity (VC). In 16 patients
      the two subcomponents of DLCO, i.e. alveolar-capillary membrane diffusion (Dm)
      and diffusion related to capillary volume (Cv), were analyzed. Patients were
      grouped for Ctr (> or = 60%, Group 1, n = 28 and < 60%, Group 2, n = 25): VT
      (Group 1 0.62 +/- 0.2 l; Group 2 0.76 +/- 0.2 l, p < 0.01); Va (Group 1 4.21 +/-
      0.97 l; Group 2 5.37 +/- 1.12 l, p < 0.0001); VC (Group 1 2.3 +/- 0.6 l; Group 2
      3.1 +/- 0.6 l, p < 0.0001); DLCO (Group 1 16.15 +/- 3.95 ml/min x mmHg; Group 2
      22.24 +/- 6.57 ml/min x mmHg, p < 0.0001). An inverse correlation was observed
      between Dm and Ctr (r = -0.47, p < 0.02), which disappeared when Va was accounted
      for Dm/Va (r = -0.12, NS). Cv was lower in Group 1 vs Group 2. In conclusion, in
      patients with Ctr > or = 60% (Group 1) "anatomy" (VT, Va, VC and Cv) and function
      (DLCO) of the lungs are impeded. This is likely due to reduction of space
      available for the lungs in the thorax by an enlarged heart (no correlation
      between Dm/Va vs Ctr).

PMID- 9611859
TI  - [Chronobiology of acute pulmonary edema in an emergency service].
AB  - Some diseases like acute myocardial infarction, sudden death and stroke have been
      reported to disclose daily, weekly or annual incidence fluctuations. We analyzed
      the rhythm of pulmonary edema occurrence. We considered 105 consecutive subjects
      (mean age 73.7 +/- 9.7 years) who came to an Emergency Department because of
      acute pulmonary edema during a solar year. Chronobiologic analysis was performed
      using Halberg single cosinor test. Pulmonary edema incidence was higher during
      the night with an acrophase at 2:14 a.m. (p < 0.001). No significant weekly or
      circannual rhythms were detected. We discuss the possible relations with
      diminished heart output, increase in sympathetic tone or partial baroceptor
      desensitization, occurring at night.

PMID- 9611860
TI  - [Nonobstructive cor triatriatum].
AB  - Our experience refers to a 50-years-old man with isolated nonobstructive cor
      triatriatum sinistrum. He was evaluated casually for essential hypertension.

PMID- 9611861
TI  - [The nephrologist].

PMID- 9611862
TI  - Botulism associated with home-preserved mushrooms.

PMID- 9611863
TI  - London antenatal clinics should offer and recommend HIV testing.

PMID- 9611864
TI  - CTNURS-L: development of a statewide communication network for nurses in
      Connecticut.

PMID- 9611865
TI  - Designing a computer-based clinical learning lab for staff nurses.

PMID- 9611866
TI  - Perceived ease of use and usefulness of bedside-computer systems.
AB  - Many new technologies are being developed to improve the efficiency and
      productivity of nursing staff. A key to the success of these technologies is
      acceptance by nurses. Davis' constructs of perceived ease of use and perceived
      usefulness were developed to measure the acceptance of computer systems. This
      article presents a discussion on nursing acceptance of computer systems, reviews
      the development of the perceived ease of use and perceived usefulness measures,
      and reports findings of a study based on these constructs along with attitude of
      bedside-computer systems. Results of the study showed that nurses in general are
      accepting of bedside-computer technology.

PMID- 9611867
TI  - ANA standards for nursing data sets in information systems.
AB  - The American Nurses Association has established the Nursing Information and Data
      Set Evaluation Center. The purpose of this Center is to develop and disseminate
      standards pertaining to information systems that support the documentation of
      nursing practice, and to evaluate voluntarily submitted information systems
      against these standards. The need for an evaluation center arises out of a long
      history of calls for standards pertaining to nursing data and information
      systems. These calls have come from the Secretary of Health and Human Services
      Commission on Nursing, the National Commission on Nursing Implementation Project,
      and a joint Task Force appointed by the Congress of Nursing Practice Steering
      Committee on Databases to Support Clinical Nursing Practice and the Congress of
      Nursing Practice Committee on Nursing Practice Standards and Guidelines.
      Standards have been developed to evaluate the completeness, accuracy and
      appropriateness of four dimensions of nursing data sets and the systems that
      contain them: (1) nomenclature, (2) clinical content, (3) clinical data
      repository, and (4) general system characteristics.

PMID- 9611868
TI  - Securing the transmission and storage of medical information.
AB  - The widespread use of computer-based patient records and the increased
      implementation of telecommunications has brought to the forefront the concern of
      patient confidentiality. Without adequate security measures, a patient's medical
      information may be intercepted, accessed, modified, or deleted by an unauthorized
      individual. Although no internal control is absolute, the use of encryption is a
      powerful tool to protect data. The authors describe how encryption works and its
      role in the web of internal controls that protect medical information systems in
      general and computer-based patient records in particular.

PMID- 9611869
TI  - American Nursing Informatics Association role survey.
AB  - A descriptive study, using a survey approach, was conducted among 48 American
      Nursing Informatics Association (ANIA) member respondents to determine the
      nursing informatics role among professional nurses working in the specialty.
      Members were asked to complete a survey regarding their current position,
      educational and work experience, continuing education, and work challenges.
      Although the ages of the informatics nurses parallel the national, range, most
      have been in the field of nursing informatics for 2.5 to 5 years and in their
      current position only 1.5 to 2 years. Job responsibilities and challenges
      indicate common issues and concerns that have implications for the specialty of
      nursing informatics and nursing in general.

PMID- 9611870
TI  - [The threat of an influenza pandemic].

PMID- 9611871
TI  - [Variants of hepatitis C virus in different risk groups. Comparative study of a
      method for genotyping and another for serotyping].
AB  - AIMS: The aim of this study was to know the prevalence of the different variants
      of HCV in the Health Care area of Monforte de Lemos (Lugo, Spain) and its
      distribution according to risk factors and to compare the results obtained with
      one genotyping and one serotyping technique. PATIENTS AND METHODS: Eighty-four
      patients with hepatitis C were studied, 25 of whom were IVDA, 14 had received
      blood transfusions, 4 hemodialysis and the risk factor was unknown in 41. The
      antibodies against HCV were studied by second generation EIA and confirmed by an
      immunoblot technique. Serotyping was carried out by an ELISA test. Genotyping was
      undertaken with a reverse hybridation test of the amplification obtained by
      polymerase chain reaction prior to reverse transcription (RT-PCR). RESULTS AND
      CONCLUSIONS: The genotypes most frequently observed were 1b (47.6%), 1a (20.2%)
      and 3 (14.3%). In the IVDA patients the genotypes 1a (40%) and 3 (24%)
      predominated. The 1b genotype was the most prevalent in the patients of unknown
      risk (68.3%) and patients with a history of blood transfusion (50%). The
      prevalence of the different serotypes was similar to that of the corresponding
      genotypes, with nearly 100% agreement. The number of untypable cases was greater
      in the serotyping technique (20.2%) than in the genotyping (2.4%). A greater
      number of mixed infections was detected with serotyping (7 cases, 8.3%) than with
      genotyping (1 case, 1.2%). Lesser sensitivity of the serotyping test was observed
      in the patients lacking anti-NS4 antibodies.

PMID- 9611872
TI  - [Psoas muscle abscess. Description of a series of 19 cases].
AB  - Abscess of the psoas muscle (PA) is every more frequently observed in recent
      years. The PA diagnosed in the authors' center over a period of 91 months are
      presented, analyzing the main clinical features, microbiologic causal agents,
      risk factors, treatment and the differences between primary and secondary PA. A
      total of 19 cases of which 14 were secondary PA (73.7%) and 5 primary PA (26.3%)
      were diagnosed. The main foci of infection of the former were the bone and the
      genitourinary tract, with intestinal infection being rare. The most frequent
      clinical data were lumbar pain with possible irradiation to the lower limb,
      fever, and leucocytosis with neutrophilia. Gram negative and enteric anaerobes
      were the bacteria most often identified, followed by Staphylococcus aureus and
      Mycobacterium tuberculosis. In a high percentage of patients (57.8%) a history of
      immunodeficiency was reported. In regard to treatment, surgical drainage was
      performed in 5 cases (26.3%), while ten cases (52.6%) were treated by DPCT. Four
      patients (21%) were exclusively treated with antibiotics. Recurrence was observed
      in three cases (15.3%) of the DPCT group requiring new drainage. Of all the
      cases, 18 were cured while one death occurred, being attributed to the underlying
      tumoral disease of advanced stage. The authors believe DPCT to be a good
      therapeutic option in both primary and secondary PA, thereby avoiding the risks
      of major surgery. In the cases with no underlying immunodeficiency the existence
      of secondary PA should be discarded as occurred in 7 out of 8 cases with no
      history of immunodeficiency in this series of patients.

PMID- 9611873
TI  - [Dog bite infections associated with CDC group EF-4a. Report of 2 cases].
AB  - BACKGROUND: Group EF-4 bacteria make up part of the normal flora of the oral
      cavity of dogs and cats. Few reports have been published on the incidence of
      human infections by this group of bacteria and these are associated with animal
      bite or scratch. Two cases of infections by CDC group EF-4 by dog bite were
      diagnosed in 1996 by the Bacteriology Laboratory of the authors' hospital. These
      cases are herein described and the biochemical analysis and profile of
      sensitivity of this little known group of bacteria evaluated. METHODS: Two
      clinical cases of infection by CDC group EF-4a by dog bite are described.
      Identification of the bacteria was performed by conventional biochemical tests
      and quantitative antibiotic sensitivity to 12 antibiotics was carried out by the
      seried broth macrodilution method. RESULTS: The two strains isolated corresponded
      to biovar "a" of group EF-4 being sensitive to: ampicillin, ceftriaxone,
      aminoglycosides, chloramphenicol, rifamipicin, TMS and ciprofloxacin,
      intermediate sensitivity to erythromycin and were resistant to cefalotine,
      oxacillin and vancomycin. With respect to penicillin, one of the strains was
      sensitive and the other presented intermediate sensitivity. Neither of the
      strains produced beta lactamase. CONCLUSIONS: Although Pasteurella sp. is usually
      considered in dog bite wounds, the possible presence of group EF-4 should be
      taken into account since the sensitivity of both microorganisms against
      penicillin and cefalotin, which are effective against Pasteurella but less active
      against group EF-4 bacteria differ.

PMID- 9611874
TI  - [Thrombosis of the hepatic artery and portal vein secondary to invasive
      aspergillosis following liver transplantation].
AB  - Thrombosis of the main hepatic vessels is a severe, frequent complication in
      patients requiring liver transplantation. It is usually a cause of emergency
      retransplantation. Two cases of hepatic vascular thrombosis secondary to
      disseminated aspergillosis are presented. Both patients demonstrated a septic
      state and required a second transplantation despite which they died within a few
      days. Necropsy showed disseminated aspergillosis with invasion of the portal
      venous system and the hepatic artery. The risk factors associated with this
      infection and the possible pathogenic mechanisms are discussed.

PMID- 9611875
TI  - [Serologic cross-reactions to Leishmania infantum using indirect
      immunofluorescence in HIV+ and HIV- patients with active tuberculosis].
AB  - BACKGROUND: Clinical presentation of disseminated tuberculosis and visceral
      leishmaniosis can be very similar, mainly in those infected with HIV, being
      serology a useful tool in making a differential diagnosis. Cross-reactions of
      IFAT serodiagnosis of visceral leishmaniosis with other diseases are well known,
      but few data is available with tuberculosis. METHODS AND RESULTS: Detection of
      serum antibodies against Leishmania, using a commercial IFAT kit, was attempted
      in sera of 51 patients with active pulmonar and/or extrapulmonar tuberculosis (25
      HIV+ and 26 HIV-). Overall cross-reactions was found in 19.6% patients without
      significative differences in between 2 groups, but differences in positive serum
      titres was observed: one at 1/256, three at 1/160, and one at 1/80 dilution, in
      the HIV+ group, whereas all 5 patients in HIV- group cross-reacted at 1/80
      dilution. Recognition of specific leishmanial antigenic bands by serum antibodies
      of patients with tuberculosis were not clearly defined by Western-blot.
      CONCLUSIONS: IFAT technique for leishmaniosis cross-react in 20% of patients with
      tuberculosis.

PMID- 9611876
TI  - [Recurrent infection by Streptococcus agalactiae].
AB  - BACKGROUND: To study the factors implicated in the infectious process (host,
      microorganism and antibiotic) of a newborn early sepsis by S. agalactiae that
      suffered a reactivation at day five from discharge. METHODS: Description of two
      episodes of newborn sepsis by S. agalactiae corresponding to the same patient and
      microbiologic study of the isolated strain: typing by "genomic macrorestriction"
      and antibiotic tolerance by "timed killing curves". RESULTS: It was demonstrated
      that both strains of S. agalactiae type la/c belonged to the same clone as well
      as the tolerance to ampicillin of the strain. DISCUSSION: This sort of infections
      processes in the newborn are very serious and there is possibility of relapse.
      Thus, it is important to study the ethiologic agent and its relationship with
      antibiotics, in order to stablish the best treatment regimes, avoiding the
      possibility of relapses as the case we have described.

PMID- 9611877
TI  - [Meningitis caused by enterovirus in a pediatric hospital: experience in 1996].
AB  - BACKGROUND: To know the incidence, etiology to the serotype level and
      epidemiological characteristics of cases of enteroviral meningitis diagnosed in a
      pediatric emergency service in 1996. METHODS: Inoculation of conventional cell
      cultures with samples of cerebrospinal fluid (CSF), throat swabs and stools taken
      from children with clinically suspected meningitis. RESULTS: Enterovirus was
      cultured from 17 of 65 (26.2%) CSF samples with pleocytosis (more than 10
      cells/mm3) and from 12 of 268 (4.5%) biologically normal samples. The identified
      isolates of CSF (20 of 29) were: ECHO 30 (9), ECHO 11 (7), ECHO 9 (3) and ECHO 7
      (1). Most (79%) isolates were obtained between March and June. CONCLUSIONS:
      Enteroviral meningitis was apparently more common in spring, although the number
      of samples was significantly lower during the summer months. The clinical cases
      were sporadic, due to at least four echoviruses serotypes. The isolation of
      enterovirus from CSF without pleocytosis is not exceptional (41% of our
      isolates).

PMID- 9611878
TI  - [Penetration and intracellular activity of fluoroquinolones].

PMID- 9611879
TI  - [Patient with recurrent pneumonia and a mediastinal mass].

PMID- 9611881
TI  - [Infection of the wrist by Mycobacterium fortuitum].

PMID- 9611880
TI  - [Young man with bilateral pulmonary infiltrates and liver involvement].

PMID- 9611882
TI  - [Bacteremia caused by Stomatococcus mucilaginosus in a bone marrow
      transplantation patient].

PMID- 9611883
TI  - [Endocarditis caused by Listeria monocytogenes on a prosthetic valve:
      presentation of a case and review of the bibliography].

PMID- 9611884
TI  - [Pubic osteitis caused by Staphylococcus lugdunensis].

PMID- 9611886
TI  - [Endocarditis caused by Lactobacillus casei. Apropos of a case].

PMID- 9611885
TI  - [Paraparesis as the main manifestation of brucellosis].

PMID- 9611887
TI  - [Desensitization with sulfadiazine in a patient with cerebral toxoplasmosis
      refractory to alternative treatment].

PMID- 9611888
TI  - [Favorable evolution of a myocardial abscess using medical treatment in an HIV
      positive patient].

PMID- 9611889
TI  - [Antibacterial activity of lactobacilli].
AB  - The antagonistic action of lactobacilli is an important factor in the protection
      of the vagina of fertile women from infection by other microorganisms. In the
      present study the authors investigated 17 strains of lactobacilli, incl. 11 of
      vaginal origin. The objective was to investigate in more detail the antibacterial
      activity of lactobacilli and to attempt to assess substances responsible for
      inhibition. The investigated lactobacilli inhibited some strains of Escherichia
      coli, Serratia marcescens, Shigella boydii, Staphylococcus aureus, Listeria
      monocytogenes, Listeria innocua and Listeria ivanovii with different intensity.
      The authors provided evidence that inhibition is due mainly to organic acids and
      to a lesser extent to bacteriocins. The authors assessed also the effect of
      enterobacteria on lactobacilli but did not observe any inhibition of
      lactobacilli.

PMID- 9611890
TI  - [Identification of Pseudomonas stutzeri with the NEFERMtest, NEFERM test 24 and
      API 20NE commercial test kits].
AB  - A total of 35 strains of Pseudomonas stutzeri were tested by commercial
      diagnostic kits NEFERMtest, NEFERMtest 24 (both Lachema Co., Brno, Czech
      Republic) and API 20NE (bioMerieus sa, RCS Lyon, France). The best identification
      efficacy was achieved by means of the commercial API 20NE (97.1%). Only 60%
      strains were correctly identified by means of NEFERMtest. NEFERMtest 24 improved
      successful identification (80%). Most misidentified strains were identified as
      Alcaligenes denitrificans and Al. xylosoxidans.

PMID- 9611891
TI  - [Educational status of the Czech population about Lyme borreliosis and experience
      with tick bites--pilot study].
AB  - The incidence of Lyme borreliosis (LB) has a rising trend since 1995. In 1995
      6,302 cases were reported, in 1996 4,192 (EPIDAT, SZU). The objective of the
      present work was to assess in a selected population sample knowledge of ticks and
      their relationship to Lyme borreliosis. The investigation was based on a survey
      using questionnaires. 110 respondents were selected according to the following
      pattern: 19 secondary school students, 32 blood donors, 44 visitors of parks, 15
      countryside people. 99.1% of the subjects knew about the existence of ticks in
      the Czech Republic, 10.9% of the respondents do not know about Lyme borreliosis.
      More than 80% of the people are in the countryside at least once a week. 87% of
      the people report they had a tick, 75% removed a tick from another person. Only
      6.7% of the respondents never had any contact with ticks. When removing ticks 17%
      of the subjects use disinfection, 67% use oil. Almost 30% of the respondents
      remove ticks with bare hands and more than 14% destroy them by squashing them
      between their fingers. 41% are not aware of the risk of transmission of tick
      borne encephalitis. From the investigation a frequent contact of the population
      with ticks is apparent. Theoretical knowledge of the problem is extensive,
      practical experience is different. Unfortunately unsuitable habits in removal of
      ticks persist and this increases the risk of transmission of Lyme borreliosis.

PMID- 9611892
TI  - [Salmonellosis in children under 2 years of age].
AB  - The authors pay attention to the mode of transmission of salmonelloses in
      children under two years of age, where the highest specific morbidity was
      recorded. Using phenotypic (biochemical properties, sensitivity to antibiotics,
      phagotype) and genotypic properties (presence of plasmids) they examine five
      sporadic and seven epidemic incidences of salmonelloses in young children. The
      most frequent agent is Salmonella enteritidis, phagotype 8, plasmid 55 kb.
      Strains of S. enteritidis are isolated from the faeces of affected children,
      their family contacts, from food and the sick child's environment. Alimentary
      transmission by the incriminated food was detected from epidemic incidence where
      the vehicle were confectionery products contaminated by S. enteritidis. In
      sporadic cases in families also direct and indirect contact may have participated
      in the transmission of infection.

PMID- 9611893
TI  - [Identification of Salmonella typhi phage types 1991-1996 in the Slovak
      Republic].
AB  - A total of 102 strains of Salmonella typhi were received at the National
      Salmonella Phage Typing Centre at Bratislava during January 1991-December 1996
      from various regions of the Slovak Republic. From these, 24 strains were isolated
      and confirmed by cultivation from patients with typhoid fever and 78 strains were
      isolated from chronic carriers. According to the results of Vi-phage typing the
      strains belonged to 9 phage types. A predominance of phage types E1/a (24.5%), D1
      (18.6%), A (13.7%) and F1 (12.7%) was observed. Another three groups were formed
      by the strains described as I + IV, strains of with atypical lytic reaction
      (RDNC) and Vi-negative strains. In the case of three chronic carriers a change of
      the originally established phage type to another phage type was observed after
      many years. This genetical problem should be kept in view in epidemiological
      practice, especially in the study of the phage types of Salmonella typhi strains
      isolated from long-term carriers.

PMID- 9611894
TI  - [Sensitivity to disinfectants in certain rare micromycetes].
AB  - The authors investigated the effectiveness of 6 different disinfectants at
      recommended concentrations on strains of rare types of filamentous micromycetes:
      Scedosporium apiospermum and Exophiala dermatitidis (isolated from
      ophthalmomycoses), Fusarium dimerum (isolates from nosocomial fungaemia) and
      strains of Fusarium moniliforme and Stachybotrys alternans (isolates from the
      environment and potential producers of mycotoxins). The tested strains were
      mostly sensitive also to an alcoholic solution, to a preparation containing
      glutaraldehyde, with inorganic peroxocompounds, with peroxoacetic acid; the
      lowest effectiveness was found in the preparation containing active chlorine and
      the most resistant strain was Scedosporium apiospermum.

PMID- 9611895
TI  - [Molecuar epidemiology of tuberculosis].
AB  - Tuberculosis is a serious disease, killing many people every year. After decades
      of progressive decrease this disease, boosted by the appearance of HIV, reemerges
      showing a marked upward tendency and most afflicting populations in developing
      countries. At present, many researchers have been involved in molecular
      epidemiology of tuberculosis using DNA fingerprinting to determine restriction
      profiles of different strains. This method has also proved useful in detecting
      outbreaks of the disease in populations. That is very important for determining
      primary infection sources and their subsequent elimination from the environment
      to prevent recurrent infections.

PMID- 9611896
TI  - [Should epidemiologists be pragmatists, biostatisticians or clinical
      scientists?].

PMID- 9611897
TI  - Medical malpractice in twentieth century United States. The interaction of
      technology, law and culture.
AB  - Although medical malpractice litigation in the United States has generated
      extensive professional and scholarly attention, few analyses of the issue have
      explored its underlying causes. This essay develops and employs an historical
      framework to explain the late 20th century phenomenon and concludes that
      widespread medical malpractice suits are the result of a combination of short
      term topical causes and long-term cultural changes that are ignored or left
      untouched by most reform efforts. Most importantly, however, the development and
      proliferation of new and improved medical technologies has played a pivotal role
      throughout the entire history of the litigation, an effect that has become most
      prominent and important in the last third of the 20th century.

PMID- 9611898
TI  - Evidence-informed patient choice. Practical issues of involving patients in
      decisions about health care technologies.
AB  - Evidence-informed patient choice involves providing people with research-based
      information about the effectiveness of health care options and promoting their
      involvement in decisions about their treatment. Although the concept seems
      desirable, the processes and outcomes of evidence-informed patient choice are
      poorly understood, and it should be carefully evaluated.

PMID- 9611899
TI  - The use of societal criteria in priority setting for health technology assessment
      in The Netherlands. Initial experiences and future challenges.
AB  - Priority setting for the evaluation of health technologies in the Netherlands is
      exclusively based on the scientific merits of individual research proposals. This
      process has not resulted in satisfactory allocation of resources. Therefore,
      societal criteria for setting priorities for health technology assessment have
      been proposed as an adjunct to scientific criteria. These societal criteria
      include the burden of disease, uncertainty about the (cost-)effectiveness of the
      intervention at issue, the potential benefits of the research project, and its
      potential impact on health care. To realize the full potential of this model for
      priority setting, a number of methodological issues need to be addressed. Joint
      efforts of researchers and policy makers in this field are necessary for future
      progress.

PMID- 9611900
TI  - The effectiveness of bone density measurement and associated treatments for
      prevention of fractures. An international collaborative review.
AB  - This review assesses the evidence regarding the effectiveness of bone density
      measurement (BDM) screening and related interventions--hormone replacement
      therapy (HRT) and intranasal salmon calcitonin (SCT[N])--in menopausal women to
      prevent fractures in later life. Data sources included systematic reviews of
      evidence and relevant primary studies identified through literature searches on
      MEDLINE and EMBASE. Study selection included trials of BDM screening programs,
      prospective studies examining the predictive value of BDM, randomized controlled
      trials, cohort studies, and case-control studies of HRT and SCT (N). The evidence
      was evaluated using a classification system incorporating study design and
      quality. Outcomes were measured in terms of relative risk of fracture for a 1 SD
      decrease in bone mineral density below the age-adjusted mean, relative risks or
      odds ratios for fractures associated with treatments, and proportion of hip
      fractures potentially prevented by BDM screening linked to treatments. Fair
      evidence from prospective cohort studies suggests that BDM can predict the risk
      of fractures, but not with high accuracy. Fair evidence from low-quality
      randomized controlled trials and observational studies suggests that HRT and
      SCT(N) are efficacious in preventing fractures. Good evidence supports the
      efficacy of these treatments in preserving bone mass, but there is fair evidence
      that the effect wears off after cessation of therapy. There is little evidence on
      the impact of screening menopausal women with BDM in association with HRT or
      SCT(N) treatment. Estimates based on combining existing evidence regarding the
      predictive value of BDM and efficacy of HRT suggests that 1-7% of hip fractures
      might be prevented.

PMID- 9611901
TI  - Estimating the costs of hip fracture and potential savings.
AB  - This paper examines the determinants of hip fracture costs and further evaluates
      potential savings in costs when the occurrence of hip fracture is prevented. The
      costs of hip fracture are comprised of direct costs from health care and the
      social welfare system. Data were collected for 1,080 postmenopausal women
      admitted from private residence for primary hip fracture surgery during the year
      of 1992 in the city of Stockholm, Sweden. It was found that the cost of hip
      fracture is significantly related to age, mortality the year after a fracture,
      type of fracture, costs 1 year before a fracture, and hospital admission. The
      savings in direct costs for an average woman surviving the year after a fracture
      amount to SEK 210,000.

PMID- 9611902
TI  - Anticipating the consequences for the primary therapy of breast cancer after
      introducing screening. A more global picture for health care policy making.
AB  - A breast cancer screening program mainly aims at reducing mortality. However, it
      also has an effect, often not assessed, on the utilization of health care
      resources that is relevant to health care policy making. Using a simulation
      model, this paper forecasts the impact of introducing a breast cancer screening
      program on the utilization of resources for the primary therapy of breast cancer.
      The most important consequences from a health care point of view will be an
      increased use of breast-conserving therapy and an increased need for
      postoperative radiotherapy; there will also be a higher number of women diagnosed
      with noninvasive breast cancer. The results of this study could provide support
      for health care decision making by showing the consequences of policy decisions
      on the introduction of screening programs for health care utilization.

PMID- 9611903
TI  - The costs of treating breast cancer in the United Kingdom: implications for
      screening.
AB  - Total treatment costs by stage at diagnosis are estimated for a sample of breast
      cancer patients. At 4 years, stage 4 cancers emerge as being more expensive to
      treat than those at earlier stages, although this difference fails to achieve
      significance when expected lifetime costs are considered. The inclusion of
      treatment cost estimates in a screening model indicates that screening may
      increase expected treatment costs by a marginal amount, although the model also
      suggests that the cost-effectiveness ratio of breast cancer screening might be
      better than had originally been thought.

PMID- 9611904
TI  - Fecal occult blood tests. A cost-effectiveness analysis.
AB  - A range of fecal occult blood tests are presently on the market and could
      potentially be used in population screening programs for the detection of
      colorectal neoplasms. This paper estimates the relative cost-effectiveness of
      alternative tests and concludes that the unhydrated Hemoccult II is the most cost
      effective. However, the incremental costs per life-year of the HemeSelect test
      and the rehydrated Hemoccult II test are in line with incremental costs observed
      in breast cancer and cervical cancer programs.

PMID- 9611905
TI  - A cost-utility analysis of abdominal hysterectomy versus transcervical
      endometrial resection for the surgical treatment of menorrhagia.
AB  - Menorrhagia, or heavy regular menstrual bleeding, represents a major health
      burden to women. Trials comparing abdominal hysterectomy (AH) with transcervical
      resection of the endometrium (TCRE) for the condition have shown that, although
      the duration and severity of convalescence is less with TCRE, AH produces a
      permanent solution to heavy bleeding while TCRE fails in a proportion of women by
      2 years. However, by 2 years, TCRE costs only 71% that of AH. This paper presents
      a cost-utility analysis to assess which procedure is more cost-effective overall.
      Under most plausible parameter values and on the basis of health state values
      elicited from a sample of women with menorrhagia, AH is likely to be considered
      more cost-effective than TCRE if purchasers are willing to pay an additional cost
      of at least 6,500 Pounds per extra quality-adjusted life-year generated by AH.

PMID- 9611906
TI  - Cost-effectiveness of cardiovascular prevention programs in Spain.
AB  - Individual programs for prevention of cardiovascular disease include dietary and
      drug treatment of hypercholesterolemia, hypertension treatment, and smoking
      cessation therapies. In this study, the cost-effectiveness of available
      cardiovascular prevention programs was assessed in Spain in terms of net cost per
      life-year gained (LYG). Cost-effectiveness ratios ranged from US $2,600 to
      $80,000 per LYG in men and from $4,500 to $230,000 per LYG in women. In men aged
      40-59 years, the ranking of increasing cost-effectiveness was: smoking cessation
      ($2,608-3,738 per LYG); treatment of moderate and severe hypertension ($8,564
      38,678 per LYG); treatment of mild hypertension ($11,906-59,840 per LYG); dietary
      treatment ($16,143-20,158 per LYG); and drug treatment of hypercholesterolemia
      ($33,850-81,010 per LYG). In women, the ranking list was:smoking cessation
      ($4,482-5,756 per LYG), treatment of moderate and severe hypertension ($9,585
      57,983 per LYG), treatment of mild hypertension ($15,248-86,075 per LYG), dietary
      treatment ($57,175-62,154 per LYG); and drug treatment of hypercholesterolemia
      ($104,100-259,150 per LYG).

PMID- 9611907
TI  - Introducing information technology in the clinical setting. Lessons learned in a
      trauma center.
AB  - Using a case study methodology, we examined the implementation of a nursing flow
      sheet system in the trauma center of a large, not-for-profit, teaching hospital.
      Findings add new insights to the existing body of knowledge in the information
      technology and medical informatics fields. First, results reveal that the success
      of clinical information systems requires a proactive stance where key actors
      anticipate and address the challenges ahead and capitalize on opportunities.
      Second, empirical evidence indicates that project outcomes ultimately depend on
      how the implementation process is managed and what the organization and its
      members do with the system once it is introduced. Finally, the case at hand shows
      that the nature and overall quality of the implementation strategy can be largely
      predicted by the key actors involved in the project, given their own background,
      skills, interest, and level of motivation.

PMID- 9611908
TI  - Technology assessment of the Dutch Lung Transplantation Program.
AB  - The costs, effects, and cost-effectiveness of the Dutch Lung Transplantation
      program were assessed. The results show that lung transplantation is a very
      costly intervention that improves survival and quality of life. Costs per life
      year and per QALY gained were, respectively, US $90,000 and US $71,000.

PMID- 9611909
TI  - Health state preferences of persons with anxiety.
AB  - We compared patient ratings of the desirability of anxiety health states with
      measures of psychological distress and functional status and investigated how
      these ratings predicted treatment by primary care and mental health clinicians.
      As expected, associations between desirability ratings and psychological and
      physical health status were low to moderate. Persons who rated their current
      anxiety health state as more desirable received fewer mental health referrals and
      were statistically more likely to receive a prescription for psychotropic
      medication. Simple ratings of health state desirability may help clinicians
      evaluate patients' views of their health status and discuss potential treatment
      options.

PMID- 9611910
TI  - When is the 'right' time to initiate an assessment of a health technology?
AB  - There is currently no generally accepted formula for the optimal timing of health
      technology assessments (HTAs). This paper presents some of the relevant issues
      and then reviews the existing literature on timing of HTAs. It finds that the
      literature that specifically addresses these issues is limited. There is a
      consensus that HTAs should be initiated at an early stage of the development of a
      new health technology, and repeated during the life cycle of the technology.
      However, the questions of reliably identifying new technologies at an early stage
      in their development and of deciding on a detectable critical point for starting
      evaluation are not resolved. It is proposed that a system of categorization and
      prioritization of health technologies should be developed to allow decisions to
      be made as to when a strongly precautionary approach is required and how the
      limited resources available for HTA could be optimally deployed.

PMID- 9611912
TI  - Report from the Swedish Council on Technology Assessment in Health Care (SBU).
      Treatment with neuroleptics.

PMID- 9611911
TI  - Evidence into practice. Prescribing selective serotonin reuptake inhibitors.
AB  - This descriptive analysis examines prescribing trends of antidepressants in
      English primary care, providing analysis of NHS reimbursement data for groups of
      antidepressants between 1989 and 1994. Prescribing trends seem unaffected by the
      release of information on the effectiveness and cost-effectiveness of
      antidepressant drugs. We found that simple distribution of the results of health
      technology assessments may not be sufficient to influence practice.

PMID- 9611913
TI  - Reports from the Canadian Coordinating Office for Health Technology Assessment
      (CCOHTA). Selective serotonin reuptake inhibitors for major depression.

PMID- 9611914
TI  - Reports from the Health Council of The Netherlands.

PMID- 9611916
TI  - Octogenarians and beyond: what eventually kills the oldest old?

PMID- 9611917
TI  - Schizophrenia: prevention and intervention.

PMID- 9611915
TI  - Report from the Spanish Ministry of Health and Consumer Affairs (Ministerio De
      Sanidad y Consumo). Efficacy of serogroup C meningococcal polysaccharide vaccine.

PMID- 9611918
TI  - Hormone replacement therapy and osteoporosis.

PMID- 9611919
TI  - Child resistant containers in the prevention of childhood poisoning.

PMID- 9611920
TI  - New developments in palliative medicine.

PMID- 9611921
TI  - Depression in the elderly revisited.

PMID- 9611922
TI  - Impotence--the present and the future.

PMID- 9611923
TI  - A 25 year review of parotid surgery.
AB  - At a single institution over 25 years, 110 patients were operated upon for a
      mixture of parotid disease. The mean duration of symptoms for benign disease was
      40.8 months compared with 15.6 months for malignant disease. Pain was a
      significant feature of malignant parotid disorders (46.1% compared with 17.8% for
      benign conditions). The pathology of these masses was diverse, with pleomorphic
      adenoma being the commonest (44%). Superficial parotidectomy was the commonest
      procedure employed (69/110) with local excision being performed only prior to
      1984 (15/110). There were five cases of permanent facial palsy, all following
      radical resection for malignancy. One patient developed Frey's syndrome.
      Recurrence rate for pleomorphic adenomas was 7/48 (15%), three following
      enucleations prior to 1984. In primary malignancy of the parotid, 3/21 (14%)
      developed recurrences. Parotid tumours have a low incidence. Surgery for these
      tumours can be safely performed by those with a special interest in parotid
      surgery.

PMID- 9611924
TI  - Unilateral papilloedema in a 12 year old girl--a surprising diagnosis.
AB  - A previously well 12 year old girl presented with diminished visual acuity and
      haziness of her left eye. Her examination confirmed visual loss in her left eye
      and significant disc blurring on fundoscopy. Extensive investigations including
      computerised tomography of the brain and orbit were normal. Her serum angiotensin
      converting enzyme (ACE) levels were elevated and subsequent Kveim test was
      positive confirming the diagnosis of ocular sarcoidosis. She did respond to a
      course of systemic steroids and over the following 3 years her eye signs and
      symptoms did correlate well with the ACE level. To date she has not had any
      systemic or respiratory symptoms. Thus sarcoidosis should be considered in the
      differential diagnosis of ocular pathology of unexplained aetiology.

PMID- 9611925
TI  - The provision of influenza vaccine to patients over 65 years by general
      practitioners.
AB  - Influenza vaccination for all elderly persons is cost effective. Guidelines in
      Ireland recommend the vaccine for those with chronic illness and to the elderly
      in care. The aims of this study are to identify how influenza vaccine is provided
      to elderly patients and to get GPs opinions on what barriers there are to
      providing the vaccine to persons 65+ years. Of the 143 GPs contacted 117 (81.8%)
      replied, of whom 116 (99.1%) provide the vaccine to their patients. Ninety nine
      (85.3%) believe it to be effective in preventing influenza, and only 8 (6.9%)
      have reservations about the vaccine. Eighteen (15.5%) GPs had a difficulty in
      identifying those to be vaccinated and only 11 (9.5%) had a computerised system
      to assist them. Twenty two (19.0%) GPs had difficulty in getting sufficient
      vaccine for their patients. Ninety six (82.8%) GPs make the vaccine available to
      those for whom it is recommended and of these 61 make it available to all
      patients over 65 years. The main patient barriers to an influenza vaccination
      programme are the patients fear of getting influenza from the vaccine and that
      many patients do not consider the vaccine to be of value. Barriers identified for
      GPs are the low level of reimbursement to GPs for vaccinating eligible patients
      and the lack of proper systems that help identify and contact those who should be
      getting the vaccine. All of the barriers identified should be easy to overcome so
      that those who require influenza vaccine can reap the health and social gains
      that our health services advocate.

PMID- 9611926
TI  - Congenital anomalies in the Irish traveller community.
AB  - A national population based study of the health of Irish travellers has been
      carried out. The prevalence of congenital anomalies in this population has been
      compared to the general population in the Eastern Health Board region. The
      prevalence of congenital anomalies in travellers was 5.5%, compared to 2.9% in
      the Eastern Health region, an odds ratio of 1.95. When metabolic conditions were
      excluded there were no significant difference. There was a trend, not reaching
      statistical significance, for the prevalence of congenital anomalies among
      travellers to be greater in offsprings of first cousin marriages (6.5%) then in
      those born to unrelated parents (3.8%), on odds ratio of 1.73. A balance needs to
      be sought between being sensitive to cultural reasons for consanguinity and
      giving information to communities about the negative health consequences of
      certain cultural practices.

PMID- 9611927
TI  - Elective tracheal intubation in cervical spine injuries.
AB  - Patients presenting for surgical stabilisation of an unstable cervical spine are
      at risk of sustaining a further iatrogenic spinal cord injury during intubation
      of the trachea. Controversy exists regarding the optimal anaesthetic technique
      for securing the airway. We reviewed the techniques employed for intubating the
      trachea in our hospital over a five year period. Tracheal intubation was achieved
      using two different techniques: awake fibre-optic intubation with local
      anaesthesia, and general anaesthesia via the intravenous or inhalational route
      with neuromuscular blockade. Forty five patients were included. 16 patients
      demonstrated a pre-operative neurological deficit. Awake fibre-optic intubation
      was used in 27 cases, general anaesthesia was employed via the intravenous route
      in 17 cases and the inhalational route in 1 case. Weighted traction was employed
      in all cases to immobilize the cervical spine during intubation. There was no new
      neurological sequelae with any of these techniques. Our study suggests that there
      is no optimal anaesthetic technique for intubating the trachea in patients with
      cervical spine injuries and it is noteworthy that in line traction was used in
      every case.

PMID- 9611928
TI  - Knowledge and use of peri-conceptional folic acid among antenatal patients.
AB  - Peri-conceptional folic acid can prevent more than half of all neural tube
      defects (NTDs). A cross-sectional interviewer administered study was undertaken
      among 300 women attending their first antenatal appointment in the three major
      Dublin maternity hospitals. The aim of the study was to monitor knowledge and
      behaviour with respect to peri-conceptional folic acid among antenatal patients.
      There was a 98% (295/300) response rate. 53.6% (158/295) had heard of folic acid.
      Such knowledge was significantly associated with age over 30 years (p < 0.001), a
      planned pregnancy (p < 0.001) and being married (p < 0.001). The majority (58.2%)
      found out about folic acid from lay sources such as friends or the media. One
      eighth (12.9%, 38/295) had been advised to take folic acid before pregnancy, the
      majority (58.3%, 21/38) having been advised by doctors. 21% (62/295) knew that it
      prevented spina bifida. 5.8% (17/295) had taken it before becoming pregnant.
      Taking folic acid before pregnancy was significantly associated with having a
      planned pregnancy (p < 0.005) and being married (p < 0.005). This study
      highlights the poor impact of health promotion campaigns to date and provides a
      challenge to health professionals.

PMID- 9611929
TI  - Medical confidentiality in the doctor-patient relationship.

PMID- 9611930
TI  - The impact of a bedside decision support computer program (DSCP) on coronary
      care.

PMID- 9611931
TI  - Contemporary health practices in Ireland: manual versus non-manual differences.

PMID- 9611932
TI  - Dental materials: 1996 literature review. Part 2.
AB  - This critical review of the published literature on dental materials for the year
      1996 has been compiled by the Dental Materials Panel of the UK. It continues the
      series of annual reviews started in 1973 and published in the Journal of
      Dentistry. Emphasis has been placed upon publications which report upon the
      materials science or clinical performance of the materials. The review has been
      divided by accepted materials classifications (fissure sealants, glass
      polyalkenoate cements, dentine bonding, dental amalgam, endodontic materials,
      casting alloys, resin-bonded bridges and ceramo-metallic restorations, ceramics,
      denture base resins and soft lining materials, impression materials, implants
      materials, orthodontic materials, biomechanics and image processing, resin
      composites and casting investment materials and waxes). Three hundred and
      thirteen articles have been reviewed.

PMID- 9611933
TI  - The analysis of restoration survival data in split-mouth designs.
AB  - OBJECTIVE: To report methodological difficulties with restoration survival data
      in controlled clinical trials on Class II amalgam restorations using a split
      mouth design. The advantages and disadvantages of different ways of handling
      these data are described. METHODS: Three statistical methods (Kaplan-Meier
      estimation, logistic regression with random component and Friedman's statistic)
      are compared using data from a controlled clinical trial in which cavosurface
      angle (regular or non-standard) and cavity wall finish (applied or not applied)
      determine four treatment modalities of New True Dentalloy restorations. RESULTS:
      In this study logistic regression with a random component yields the best
      interpretable results. Cavity wall finish in combination with a regular
      cavosurface angle is indicated as the worst and cavity wall finish in combination
      with a non-standard cavosurface angle as the best treatment when the criterion is
      replacement or not within 15 years. CONCLUSIONS: The dependency between
      restorations within a patient needs to be taken into account. Logistic regression
      with a random component may be a valuable alternative to very advanced
      statistical survival modelling when restricting the research question to
      replacement within a certain time interval is not a major problem.

PMID- 9611934
TI  - Denture plaque--past and recent concerns.
AB  - OBJECTIVE: This paper critically reviews the history of denture plaque and
      identifies some concerns with the presence of Candida in the mouth. DATA SOURCES:
      This review covers literature sources related to Candida albicans and its
      relationship to denture plaque. STUDY SELECTION: The articles selected for this
      review are from referred journals and describe C. albicans and its relationship
      to oral, gastrointestinal and pleuropulmonary infections. The relationship to
      caries, root caries and periodontal disease is also covered. CONCLUSIONS: Denture
      plaque containing Candida could cause not only oral candidiasis, like oral thrush
      or denture-induced stomatitis, but also caries, root caries and periodontitis of
      abutment teeth. However, there is only limited experimental evidence or
      information available on the cariogenicity of Candida. The continuous swallowing
      or aspiration of micro-organisms from denture plaque exposes patients,
      particularly the immunocompromised host or medicated elderly, to the risks of
      unexpected infections. The term, 'denture plaque' has been used throughout the
      review. However, the term 'plaque on denture' should be used because the
      microbial flora and its pathogenicity of denture plaque resembles those of plaque
      formed on the tooth surface, so called dental plaque. In addition, the term
      'denture related stomatitis' would be preferable to 'denture induced stomatitis',
      since the inflammation of (palatal) mucosa is not induced by the denture, but by
      wearing the denture or by plaque on the denture.

PMID- 9611935
TI  - Neural networks: a new technique for development of decision support systems in
      dentistry.
AB  - OBJECTIVES: To outline the key concepts of neural network based systems and to
      evaluate the potential applications of such systems in dentistry. DATA SOURCES:
      Published work on neural networks. CONCLUSIONS: Neural networks may initially
      seem complex and computer intensive, but actually integrate well with a clinical
      environment. Neural network expert systems may be trained with only clinical data
      and as such can be used where 'rule based' decision making is not possible. This
      is the case in many clinical situations. Neural networks may therefore become
      important decision making tools within dentistry and have applications both in
      improving clinical care and in maximizing the cost benefit of care.

PMID- 9611936
TI  - A clinical evaluation of posterior composite resin restorations: 8-year findings.
AB  - OBJECTIVES: From a continuing investigation of the clinical performance of three
      different types of composite resin, the findings of the clinical evaluation at 8
      years are presented. METHODS: One operator placed 330 restorations in Class I and
      Class II preparations in the posterior teeth of 72 patients. Every patient
      received at least one restoration of each type of material: a microfilled
      composite, a small particle hybrid, a relatively coarse particle hybrid, and an
      amalgam control. Restorations were evaluated using clinical criteria. RESULTS:
      Forty six patients attended the 8-year recall. Twenty-five of the 213
      restorations (13.7% of the composites and 5.8% of the amalgams) originally placed
      in these 46 patients had previously failed or been lost from the study or were
      assessed as requiring replacement at the 8-year recall. Bulk fracture and
      secondary caries at the margin were the most common forms of failure in the
      composite restorations. Other failures or losses were associated with a non
      margin defect in the composite, caries not associated with the restoration,
      pulpal considerations, extraction for orthodontics and reasons unknown. One
      hundred and ninety-three restorations (including five that required replacement)
      were available for clinical evaluation at 8 years and these included 17 Class II
      restorations. Significantly fewer restorations placed with the coarse particle
      hybrid exhibited evidence of marginal deterioration. CONCLUSION: At 8 years,
      composite restorations in posterior teeth had failed at a rate two to three times
      that of amalgam restorations. The most common types of failure were bulk fracture
      and secondary caries at the margin.

PMID- 9611937
TI  - A radiographic and scanning electron microscopic study of approximal margins of
      Class II resin composite restorations placed in vivo.
AB  - INTRODUCTION: Clinical studies on the quality of Class II amalgam and resin
      composite restorations frequently report defective cervical margins. AIM: The aim
      of this study was to evaluate the quality of the approximal margins of Class II
      resin composite restorations placed in vivo using various application techniques
      and adhesive systems. MATERIALS AND METHODS: Class II restorations were placed in
      premolar teeth in vivo, using different adhesive systems and application
      techniques. After extraction of the teeth, the restorations were evaluated
      radiographically and by SEM. RESULTS: One-hundred and forty-four resin composite
      Class II restorations were evaluated. According to the radiographs, 4% of the
      restorations were overfilled and 33% were underfilled. SEM pictures revealed that
      43% of the restorations were overfilled and 25% underfilled. Thirty-two per cent
      of the restored teeth showed a flash of bonding agent on the approximal surface.
      CONCLUSIONS: Class II resin composite restorations placed in vivo may be found
      frequently to show imperfect cervical margins. Overextended margins observed by
      SEM are difficult to detect on radiographs. When seen on a radiograph, a thick
      layer of bonding agent may be interpreted as an underfilled restoration.

PMID- 9611938
TI  - A method to measure clinical erosion: the effect of orange juice consumption on
      erosion of enamel.
AB  - OBJECTIVE: Acidic soft drinks are frequently implicated in dental erosion, but
      there are limited supporting data. Research is problematic due to the insidious
      nature of erosion and accuracy in assessing tissue loss. The aim of this study
      was to develop and validate, using a negative control, a model to accurately
      measure erosion in situ due to a single aetiological agent over a relatively
      short time period. METHODS: An intra-oral appliance capable of retaining an
      enamel sample was designed in order to assess the effect of orange juice
      consumption on enamel. The study was a single centre, randomized, placebo
      controlled, blind, crossover design. RESULTS: Ten subjects, each consuming 11 of
      orange juice per day for 15 days, showed significantly more erosion on the enamel
      specimens than the same subjects consuming 11 of water per day over the same time
      period, measurements undertaken with surfometry. The same investigation was
      performed in vitro. Again, orange juice was significantly more erosive; indeed,
      it was in the order of 10 times that produced in situ. Surface microhardness
      testing in situ and in vitro demonstrated statistically significant differences
      between exposed and unexposed areas after orange juice treatment. CONCLUSIONS:
      Changes produced by water either in situ or in vitro were always well within the
      baseline measurement parameters (+/- 0.3 micron) set down for the method and
      hence validated the clinical model in terms of reproducibility and accuracy in
      measurement. It is concluded that this method has confirmed the erosive potential
      of orange juice in situ. The method could have many applications to study dental
      erosion under highly controlled conditions and over realistic time periods.

PMID- 9611939
TI  - The relationship between mandibular bone mineral density and panoramic
      radiographic measurements.
AB  - OBJECTIVES: To compare densitometric and linear measurements (mandibular cortical
      thickness, MCT; panoramic mandibular index, PMI) made from dental panoramic
      tomograms (DPTs) with bone mineral density (BMD) values obtained using dual
      energy X-ray absorptiometry (DXA) of the mandible and to determine whether
      measurements from DPTs have validity in predicting BMD. METHODS: Forty edentulous
      female patients were examined by a DPT incorporating a nickel step wedge and by
      DXA of the mandible. In each case the equivalent nickel thickness of sites in the
      mandibular body, MCT and PMI values were calculated and their relationship with
      DXA measurements assessed. RESULTS: Densitometric measurements of DPTs did not
      correlate with mandibular BMD. MCT significantly correlated with mandibular BMD
      (r = 0.50, P = 0.001 and r = 0.36, P = 0.021 for repeated measurements) as did
      PMI (r = 0.37, P = 0.019 and r = 0.38, P = 0.016 for repeated measurements). All
      three measurements from DPTs had limited repeatability. MCT and PMI had moderate
      sensitivity and specificity for diagnosis of low mandibular BMD. Using ROC
      analysis, MCT and PMI measurements of one observer were significantly more valid
      than densitometry for diagnosis of low mandibular BMD. CONCLUSIONS: It may be
      feasible to use MCT and PMI as diagnostic indicators of mandibular BMD, but
      further work is required to overcome problems with repeatability and to provide a
      larger patient sample.

PMID- 9611940
TI  - Meta-analysis of anterior veneer restorations in clinical studies.
AB  - OBJECTIVES: To make an inventory of clinical studies on veneer restorations (VRs)
      using a meta-analysis review procedure and to aggregate an overall survival
      result for four types of VRs. METHODS: From the dental literature published from
      1983 to November 1996, papers were selected using an in- and exclusion protocol
      in a two-step procedure. Additionally, the papers selected were subjected to a
      quality assessment. Although not all studies used an identical definition of
      'failure of a restoration', this item was chosen to be the common study outcome.
      After a homogeneity test, cumulative survival curves were constructed by pooling
      the data from the studies. RESULTS: On a 0-1 scale, the weighted overall mean
      quality score of the studies was 0.57 (s.e. 0.09). There was adequate agreement
      between the independent assessors. The results of the quality assessment could
      not be used as weights for the survivals, but the quality outcome supports the
      description of the sample of studies. From the nine studies on porcelain VRs, the
      pooled cumulative proportion of survival after 3 years was 0.92 (s.e. 0.01) and
      from three studies on preformed acrylic VRs this figure was 0.74 (s.e. 0.03).
      From both direct and indirect resin composite VRs, data from only one study were
      available after 2.5 and 2 years, respectively. CONCLUSION: The evaluative and
      statistical basis of clinical VR studies may be improved to obtain an effective
      inference of the results. Furthermore, porcelain VRs show acceptable longevity
      after 3 years, which appears to be better than that of preformed acrylic VRs.

PMID- 9611941
TI  - Fluoride release from glass-ionomer and compomer restorative materials: 6-month
      data.
AB  - OBJECTIVES: To investigate the daily fluoride release of two glass ionomers
      (Ketac-Fil and ChemFil Superior) and two compomers (Compoglass and Dyract
      Restorative) over 6 months. METHODS: A pilot study evaluated the time taken for
      sample solutions to equilibrate to establish an appropriate time period for
      sample solution storage between fluoride ion measurements. In the main study
      storage water replacement and fluoride ion determination was made daily using a
      specific ion electrode, TISAB buffer and standard solutions for calibration.
      RESULTS: Equilibration of fluoride concentration in aqueous solution occurred in
      under 48 h for all materials. Total fluoride released (microgram mm-2) after 6
      months by Ketac-Fil (30.6, s.d. 4.9) was significantly greater than ChemFil
      Superior (12.7, s.d. 2.5), Compoglass (10.4, s.d. 1.0) and Dyract Restorative
      (7.7, s.d. 1.7) (P < 0.05). Daily fluoride release at 24 h and 10 days was
      significantly higher for the glass ionomers than the compomers (P < 0.05). After
      40 days the daily fluoride release (microgram mm-2) from ChemFil Superior (0.05,
      s.d. 0.01) was not significantly different from Compoglass (0.04, s.d. 0.01) and
      Dyract Restorative (0.03, s.d. 0.00) (P > 0.05). Daily fluoride release from
      Ketac-Fil remains significantly higher than the compomers at 3 and 6 months (P <
      0.05). CONCLUSIONS: Specimens stored in water equilibrate rapidly, suggesting the
      rate at which storage water is changed may alter the relative fluoride release
      rates of materials. This important fact is often overlooked. Fluoride release
      from the glass ionomers is initially higher than for the compomers. Fluoride
      release from glass ionomers falls rapidly to approach levels released by
      compomers. Compomers produce no initial burst of fluoride and levels of release
      remain relatively constant.

PMID- 9611942
TI  - The effect of cuspal flexure on a buccal Class V restoration: a finite element
      study.
AB  - OBJECTIVES: Failure of Class V restorations is a clinical occurrence which is
      often blamed on inadequate moisture control. However, the effects of occlusal
      forces and cuspal movement may also have an effect. The aim of this study was to
      examine the effects that cuspal movement had on the shear forces around a buccal
      Class V restoration in a lower first premolar. METHOD: A lower first premolar
      restored with a buccal Class V composite restoration and a Class I composite or
      amalgam restoration were modelled using the finite element method. The width of
      the occlusal restoration was varied from 2.1 to 3.7 mm and the depth varied from
      1.7 to 3.7 mm. RESULTS: Compared to the unrestored premolar, the presence of an
      occlusal preparation restored with composite increased the interfacial forces
      around the buccal Class V restoration by 1-67%. Similarly, the presence of an
      amalgam occlusal restoration increased the interfacial forces by 9-228%.
      CONCLUSIONS: It was found that the presence of an occlusal restoration increased
      cuspal movement, which in turn increased the shear forces around the buccal Class
      V cavity. This effect was more pronounced with increases in cavity depth compared
      to cavity width, and when amalgam was the occlusal restorative material.

PMID- 9611943
TI  - Effect of powder/liquid ratio on the clinical and laboratory performance of resin
      modified glass-ionomers.
AB  - OBJECTIVES: To compare the effects of powder/liquid (P/L) ratio and surface
      wetness on retention of adhesive Class V restorations. METHODS: One-hundred and
      six Fuji II LC restorations were placed at two clinical trial sites. In the 'high
      dry group (Site A), Fuji II LC was mixed at a P/L ratio of 3.0 and applied to
      dentine that was visibly dry, but not desiccated. In the 'low-wet' group (Site
      B), Fuji II LC was mixed at a P/L ratio of 2.25 and applied to dentine that was
      glisteningly moist. The restorations were evaluated at baseline, 1 and 2 years at
      both sites, and at 3 years at one site. The P/L ratio effects on viscosity and
      wetting were evaluated in vitro by determining the film thickness possible at
      different ratios. RESULTS: At 2 years the retention levels at the two sites
      differed significantly (p < or = 0.1). Site B ('low-wet' group) exhibited 100%
      retention, and Site A ('high-dry' group) exhibited 78% retention. At 3 years Site
      A exhibited 74% retention, and nine of the 12 retention failures occurred in
      patients 65 years and older. Laboratory measurements demonstrated that the
      viscosity of 'low-wet' mixtures permitted film thickness that were one-half those
      of the 'high-dry' group. CONCLUSIONS: The study demonstrated that a higher
      powder/liquid ratio and a drier dentine surface compromised wetting by a resin
      modified glass-ionomer resulting in a decline in retention from baseline to 3
      years. This study suggests that the dentine surface should be kept hydrated to
      promote bonding, and that the powder/liquid ratio should be low enough to create
      low-viscosity mixtures which promote wetting. In the 'high-dry' dentine group
      there was still 74% retention at 3 years, indicating that factors other than
      wetting affect retention.

PMID- 9611944
TI  - A tensile test to facilitate identification of defects in dentine bonded
      specimens.
AB  - OBJECTIVES: To determine the efficacy of a miniaturized dumbbell test procedure
      designed to more easily identify defect(s) in bonded dentine test specimens.
      METHODS: Extracted human dentine substrates were pre-conditioned with 10-3
      solution for 10, 30 or 60 s prior to dentine bonding with 4-META/MMA-TBB resin.
      Miniaturized dumbbell-shaped test specimens were prepared from the resin bonded
      samples. After 24 h storage in 37 degrees C water, the specimens were tensile
      loaded to failure. Fractured surfaces and cross-sections were examined and
      compared under scanning electron microscopy (SEM) and transmission electron
      microscopy (TEM). RESULTS: Cohesive failure within the bonding resin was observed
      in specimens pre-conditioned for 10 s. The tensile bond strength of these was
      excellent. Bond strengths of specimens that were pre-conditioned for 30 and 60 s
      were significantly lower, and defects in these specimens, formerly difficult or
      impossible to identify, were readily identified under SEM and TEM microscopy.
      CONCLUSION: The proposed method of tensile stressing to failure and
      microscopically examining fractured miniaturized dumbbell-shaped test specimens
      is a simple and reproducible test procedure. The protocol is capable of clearly
      elucidating defective resin infiltration of demineralized dentine in bonded
      interfaces. These defects are difficult to visualize by conventional and/or ISO
      recommended methods.

PMID- 9611945
TI  - Double standard in professional development.

PMID- 9611946
TI  - The American Dental Trade Association looks at dental reimbursement: responsible
      consumption of appropriate dental services. Managed Care Task Force of the
      American Dental Trade Association.
AB  - The American Dental Trade Association Managed Care Task Force has provided an
      extensive study of the effects of reimbursement on the dental profession and the
      dental trade industry. There is great variety among the needs of patients and in
      the reimbursement plans available. ADTA is urged to take a leadership position to
      ensure that programs do not restrict access, value, or quality. The key to this
      strategy will be communicating a consistent message to dentists, patients,
      benefit managers, and the research community. The message is: "Responsible
      consumption of appropriate dental services."

PMID- 9611947
TI  - Direct reimbursement--its role in financing dental benefits.
AB  - Direct reimbursement is defended against its critics. It is a benefit plan, not
      insurance, has not raised costs, is inexpensive to administer, and is popular
      with patients. The concerns of the managed care industry over dentists being
      opportunistic are unfounded in view of dentistry's outstanding ethical
      reputation. Such concerns should be more appropriately directed toward managed
      care itself.

PMID- 9611948
TI  - Position paper: dentistry and the dental industry summit on managed care.
AB  - A taskforce of dental professionals and industry leaders looked at the impact of
      dental benefit programs on America's oral health. When properly done, such
      benefits programs are positive; but precautions must be taken to ensure that
      underfunded programs and those which restrict choice are not allowed to erode
      dental health. Six possible courses of action are developed, centered around
      education, communication, and collaboration.

PMID- 9611949
TI  - A strategy for the profession and trade to deal with the changing dental
      environment.
AB  - A former plan purchaser who is now the owner of a dental laboratory explains how
      dental benefits have been frequently introduced as supplements to medical
      benefits programs by large carriers. This has created a "knowledge gap" regarding
      the effects of underfunding and restriction of choice on the oral health of
      Americans. The dental profession and the dental industry should embark on a
      program to supply the information upon which patients and employers can make
      sound decisions.

PMID- 9611950
TI  - Managing today's changing dental environment: a manufacturer's perspective.
AB  - The dental trade industry is not growing at the same rate as the profession or as
      managed care. Concerned over this trend, the American Dental Trade Association is
      looking at the changing market place in dentistry. It is apparent that managed
      care is having some impact, but its exact nature is difficult to define since
      plans are evolving. Another emerging pattern that the industry is watching is the
      growth of larger practices. These have different purchasing and marketing
      characteristics than the traditional solo practice.

PMID- 9611952
TI  - [Private medical practice within the health care system].

PMID- 9611953
TI  - Transvaginal ultrasonographically controlled aspiration of ovarian endometriomas.
AB  - Evaluation of the results of the fine needle ultrasonographically directed
      aspiration of ovarian endometriomas in relation to the efficacy of aspiration of
      the content, invasiveness, recurrences and complications. The investigation
      included 30 patients--28 with unilateral and 2 with bilateral ovarian
      endometriosis in whom 36 aspirations have been performed. Total evacuation of the
      content was achieved during the first effort in 26 patients versus 4 patients in
      whom a repeated procedure had to be done. All the patients were controlled during
      the 1 year post-aspiration period, on average. The recurrence rate was 56.66%.
      Complications have not been recorded. The transvaginal ultrasonographic fine
      needle aspiration of the ovarian endometriomas is associated with a high
      incidence of recurrences but it proved to be a simple, safe, cheap and minimally
      invasive technique which can be repeated for several times if necessary, in
      selected patients.

PMID- 9611954
TI  - [Meteorotropism in children with cerebral palsy].
AB  - INTRODUCTION: Members of the Rehabilitation team and families of children with
      cerebral palsy are daily engaged in various activities with these children.
      Weather changes (the atmospheric pressure especially) on particular days, cause
      difficult performance of anticipated therapeutic exercises, occupational therapy,
      speech therapy, education, daily living etc. The aim of this study was to
      underline the possible connection between performing daily activities of children
      with cerebral palsy and weather changes. MATERIAL AND METHODS: There were 16
      children with cerebral palsy, 2 to 14 years of age, 8 females and 8 males.
      Parents of these children got a questionnaire where they had to write down, on
      daily bases, one of the following: A--correct and easy to perform exercises, B-
      difficult to perform exercises, C--impossible to perform exercises--the child
      indisposed, for a period of three months. For the same period of time the
      atmospheric pressure changes and the temperature were recorded by a professional.
      RESULTS: Our findings are related to the relationship between the efficiency of
      physical treatment in children with cerebral palsy and meteorological phenomena.
      The weather changes did not influence about 75% of the patients. In the other
      group of patients the unsuccessful exercise was associated with periods of
      extensive cyclonic activity: 15 to 17 of March 1991 (the decrease of atmosperic
      pressure from 1010 to 999 mbara), 15 to 17 of April 1991 (the decrease of
      atmospheric pressure from 1000 to 987 mbara), 5 to 7 of May 1991 (the decrease of
      atmospheric pressure from 1000 to 987 mbara). DISCUSSION: Before and during
      cyclonic activity increases the concentration of the positive air iones which
      interferes with neuromuscular excitation and causes serotonin hyperproduction in
      the central nervous system, thus causing irritation and the lack of motivation
      for imposed demanods. CONCLUSION: About 23% of children with cerebral palsy show
      meteorotropism in terms of weather changes influencing the efficiency of
      exercises. The cyclonic activity has unfavourable influence on exercises, while
      the stable atmospheric pressure or anticyclonic activity has a favourable one in
      children with cerebral palsy who show meteorotropism. So, favourable and
      unfavourable days for therapeutic exercises can be clearly differed.

PMID- 9611955
TI  - [Idiopathic thrombocytopenic purpura in children].
AB  - INTRODUCTION: Idiopathic (immune) thrombocytopenic purpura (ITP) is the most
      frequent hemorrhagic disease in children. It represents the acquired
      megakaryocytic thrombocytopenia with the shortened life of platelets because of
      immunologic damage (antibodies absorbed by platelets). In the case of this
      acquired hemorrhagic disorder, in spite of compensatory increased function of the
      bone marrow, there is a reduced number of platelets because of their increased
      destruction by the reticuloendothelial system (destructive thrombocytopenia).
      There are three forms of ITP: acute, chronic and intermittent. The acute form
      occurs in 80-90% of cases with bleeding episodes lasting a few days or weeks, but
      no longer than 6 months. The chronic form occurs in 10-15% of children, while the
      rarest-intermittent form is characterized by periods of normalization in regard
      to the number of platelets but also with relapse in intervals of 1-3 months. The
      disease is caused by an immunological disorder in the sense of an imbalanced
      immune response. Immunologic damages of platelets cause shortening of the
      opsonized platelets life span. The most frequent platelet opsonins are the
      immumoglobulin G (IgG) antibodies directed at the platelet membrane in the form
      of autoantibodies, alloantibodies or possibly absorbed antigen caused by
      microorganism infection or drug intake. CLINICAL MANIFESTATIONS: It is typical
      for the phenomenon of bleeding that it starts suddenly and without any other sign
      of illness. The most frequent acute form appears between the second and fourth
      year, and is characterized by seasonal occurrence usually after acute viral
      infections. Children older than 10 years of age, like adults, often have the
      chronic form associated with other immunologic disorders. The disease affects
      girls more often than boys (about three times more often) with moderate and
      constant increase of antiplatelet antibodies. Hemorrhagic manifestations include:
      petechiae, purpura, epistaxis, gastrointestinal and genitourinary bleeding. They
      depend on the grade of thrombocytopenia, although there is no strict correlation
      between the number of platelets and volume of bleeding. Low mortality of the
      acute ITP is almost exclusively due to intracranial hemorrhage. LABORATORY
      STUDIES: Thrombocytopenia represents a decrease in the number of blood platelets
      being a basic abnormality of the blood count. The half-life of platelets in ITP
      is shortened. Detection of antiplatelet antibodies is connected with technical
      difficulties, so they are established in about 30% of cases. Bleeding time is
      prolonged and so is the coagulum retraction which may be completely missed. The
      Rumpel-Leede test is positive. Clinical differentiation of drug-induced
      thrombocytopenia is not possible. However, other differential diagnostic
      possibilities are thrombotic-thrombocytopenic purpura and hemolytic-uremic
      syndrome. A child with aplastic anemia or acute leukemia, beside
      thrombocytopenia, has a characteristic finding of white and red blood cell count.
      Thrombocytopenia with absent radii syndrome is associated with skeletal system
      abnormalities. TREATMENT: New knowledge about the role of the immune system in
      ITP determines the modern therapeutic modalities. In cases of acute ITP in
      children, there are two therapeutic options or therapies of choice:
      corticosteroids and high doses of intravenous immunoglobulin. Immunosupressive
      therapy means anti Rh(D) immunoglobulin, cyclosporine, cytostatics, danazol,
      loaded platelets. In cases of distinctive hemorrhagic syndrome there are also
      indications for platelet transfusion. Nowadays splenectomy is more restricted,
      because one third of cases is unsuccessful, whereas plasmapheresis is rarely used
      in children because of possible complications. CONCLUSION: ITP is the most
      frequent hemorrhagic disease in children. The disease is basically caused by an
      immunologic disorder with platelet destruction due to increased immunoglobulin on
      their membrane. (ABSTRACT TRUNCATED)

PMID- 9611956
TI  - [Alpha interferons--new therapeutic modalities].
AB  - Interferons are naturally occurring substances. In fact, interferons are
      intercellular signalling proteins produced by cells in response to various
      biological and synthetic stimuli. Three major classes of interferons have been
      identified: interferons alpha, beta and gamma. Interferons originate from natural
      sources and are products of recombinant technology. Two forms of recombinant
      alpha-interferons, 2a and 2b, are available. Alpha-interferons are secreted and
      synthetised by leucocytes and lymphoblasts. The objective herein is to review the
      current therapeutic implications of alpha-interferons. Interferons alpha have
      antiviral, anticancer and immunomodulatory activities. Clinical trials have
      proved interferons alpha to be of special value as adjuvant therapy (first line
      drugs) for hairy cell leukemia, virus hepatitis B and C and condylomata
      acuminata. The efficacy of interferons alpha is now also being evaluated in other
      malignancies and virus diseases. For instance, interferons alpha are an important
      advanced modality in the management of chronic myelogenous leukemia and can be
      considered a first-line therapy option in patients who cannot receive or relapse
      following allogenic bone marrow transplant. Of course, further research is also
      required to evaluate combination therapies with interferons alpha and other
      agents. Presently malignancies have the broadest potential in application of
      interferons alpha therapy. Hairy cell leukemia responds to interferons alpha in
      up to 90% of patients, Kaposi's sarcoma, which occurs primarily in association
      with AIDS, benefit in up to 40% of patents, lymphomas respond in about 65% of
      patients whereas chronic myelogeneous leukemia in more than 80% of patients in
      early cases. The uses of interferons alpha in infectious diseases (condylomaty
      acuminata, rhinovirus infection, protozoal, parasitic and fungal intracellular
      infections) may also be significant. However, the cost of interferons alpha is
      too high. This makes interferons alpha a second line therapy, but not in patients
      where it is more effective than alternative treatment. Interferons alpha are
      cytokines (intercellular signalling proteins) which have antiviral, anticancer
      and immunomodulatory activities. Interferons alpha therapy represents an
      important advanced modality in the management of patients with hematological
      diseases, malignancies, lymphomas, solid malignant tumours and viral infections.
      Clinical trials have proved interferons alpha to be of special value as first
      line drugs for hairy cell leukemia, virus hepatitis B and C and condylomata
      accuminata. Interferons alpha are used as single primary therapy, adjuvant
      therapy and maintenance therapy. The limiting factor for the application of
      interferons alpha is the cost of treatment.

PMID- 9611957
TI  - [Congenital toxoplasmosis].
AB  - INTRODUCTION: Toxoplasma gondii is a ubiquitous parasite of all species of
      mammals and birds (1). Most often the infection in the immunocompetent persons is
      asymptomatic. Symptoms (if present) are usually mild and self-limited. Infection
      in the fetus and immunodeficient patients may lead up to clinically severe and
      often fatal toxoplasmosis (2). ETIOLOGY: Toxoplasma exists in three forms:
      oocysts, tissue cysts and tachyzoites. The definitive hosts of Toxoplasma are
      members of the cat family. They shed unsporulated oocysts in the feces. After
      sporulation oocysts become infectious. Tachyzoites are crescent-shaped forms
      responsible for manifestations of acute Toxoplasma infection in the intermediate
      hosts (6,7). Cysts are formed, particularly in brain, heart muscle and skeletal
      muscles. The cyst forms of the parasite are seen in the latent stage of the
      infection. Postnatally acquired toxoplasmosis is a consequence of infection from
      cysts (by ingestion of undercooked meat of infected animals), oocysts (by
      ingestion of soil, fruits, vegetables contaminated by cat feces) and tachyzoites
      (by blood transfusion). Congenital Toxoplasma infection causes congenital
      toxoplasmosis. PATHOGENESIS: Some authors represented the concept that latent
      (chronic) infection with Toxoplasma during pregnancy can result in congenital
      infection in the offspring (8-11). Now it is generally agreed that congenital
      transmission of Toxoplasma occurs only when the infection is acquired during
      gestation (6,7, 12-16). More than half of the fetuses escape infection, one-third
      are definitely infected, and the infection is more often subclinical than
      clinically obvious (15). The fetus is infected hematogenously from inflammatory
      foci in the placenta formed during parasitemia in the mother. CLINICAL
      MANIFESTATIONS: Approximately 75% of congenitally infected newborns are
      asymptomatic. Wilson's study indicates that nearly all such children will develop
      adverse sequelae (neurologic, intellectual, audiologic and ophthalmologic) 21).
      Severe forms of congenital toxoplasmosis occur only in 10% of infected
      offsprings. Clinical manifestations of congenital toxoplasmosis are different.
      Clinical findings in patients with congenital toxoplasmosis may include:
      chorioretinitis and other ocular findings, central nervous system abnormalities
      (such as microcephaly, hydrocephalus, encephalomyelitis, seizures and mental
      retardation), icterus, hepatosplenomegaly, rash, anemia, erythroblastosis,
      thrombopenia. INCIDENCE: Incidence of human congenital toxoplasmosis is different
      in different countries. The incidence in Britain is 0.6 subclinical infection and
      0.09 severe illnesses per 1000 births (22). The incidence in USA is between
      1/1000 and 1/8000 live births (23). In France the incidence is 1/2000. In
      Slovenia the incidence is 2.3 cases per 1000 births (25). DIAGNOSIS: Diagnostic
      methods are: 1. Isolation of the parasite from the placenta, blood, body fluids
      (by inoculation of specimens into mice or tissue cultures). 2. Histologically by
      demonstration of tachyzoites in tissue sections or smears of body fluids. 3.
      Serologic diagnosis. The most important diagnostic methods are serologic tests.
      For diagnosis of congenital toxoplasmosis determination of IgM antibody (in the
      serum of newborn infant) has the greatest importance. The fetus is able to
      produce IgM specific antibody. The presence of IgM antibodies in serum obtained
      from the neonate is an evidence of fetus infection in utero. Maternal IgM
      antibodies do not pass the placenta. IgM antibodies may be demonstrable by
      indirect fluorescent antibody test (IgM-IFA), enzyme linked immunosorbent assay
      (IgM-ELISA), double sendwich IgM enzyme-linked immunosorbent assay (DS-IgM
      ELISA), IgM immunosorbent agglutination assay (IgM-ISAGA) and reversed enzyme
      immunoassay (REI). For diagnosis of congenital toxoplasmosis the next tests are
      also applied: Sabin-Feldman Dye test, indirect fluorescent antibody test for IgG
      antibodies (IgG-IFA) and enzyme

PMID- 9611958
TI  - [Types of medical lasers].
AB  - The knowledge about different types of lasers and their potential use in medicine
      is presented. A very rapid development of laser technology in the world imposes a
      need for up-to-date information about the characteristics of different laser
      instruments. Without this kind of information it would be difficult to keep in
      touch with the latest developments in the world's technology. Different types of
      lasers have different indication range in the medical practice. An inquiry into
      the fundamental principles of lasers physics is an important prerequisite for
      successful application of this technology in medicine. Laser as a surgical knife
      has shown certain advantages over scalpel, electrocautery and cryosurgery, as the
      laser surgery is a noncontact method, bloodless, precise, with better
      visualization, minimal postoperative edema, painless healing, without
      complications. Although laser cannot entirely replace conventional surgical
      instruments, it is still the instrument of choice for treatment of numerous
      pathological conditions. The carbon dioxide laser is a highly precise, bloodless
      light scalpel used for incising and excising tissues and sealing small blood
      vessels. The infrared beam at 10,600 nm wavelength is absorbed by water and
      tissue destruction is due to the instantaneous vaporization at relatively low
      temperature of 100 degrees C. The beam seals blood vessels of up to 0.5 mm in
      diameter and if the beam is defocused, larger vessels may be controlled. The beam
      also seals lymphatics, possibly reducing the spread of tumour cells by this
      route, and seals nerve endings: there is no incidence of neuroma formation.
      Carbon dioxide laser has shown a great efficiency in otorhinolaryngology, in
      maxillo-facial surgery and plastic surgery, in urology and gynecology. Provides
      true "no touch" surgery, and is used increasingly in neurosurgery for the precise
      atraumatic removal of tissue and for creation of precise lesions for the control
      of pain. The carbon dioxide laser beam cannot, at present, be transmitted via a
      flexible fibre, although a number of fibres are being investigated. Delivery of
      laser energy to microscope, colposcope or handpiece is via an articulated arm
      which is a hollow tube with mirrors at the articulations. The argon laser
      produces blue-green coherent light at a number of wavelengts but 80% of the
      energy is at wavelengths of 488 and 514 nm. This laser was first used in
      ophtalmology to treat diabetic retinopathy through, and without damage to, the
      clear anterior parts of the eye. The argon laser is used for blood vessel
      coagulation but can be used to perform slow, thermal tissue destruction at higher
      power levels. Argon laser is most commonly used in ophthalmology for otological
      micro-surgery, particularly in the treatment of otosclerosis and
      tympanosclerosis. Very good results have been achieved in the argon laser
      treatment of gastrointestinal bleeding ulcers, vascular lesions and polyps.
      Dermatology is another field where argon laser has shown great efficiency:
      hemangyomas, telangiectasias, tattoos, small benign and malignant tumours are
      amenable to argon laser treatment. In neurosurgery it is used to control both
      normal and abnormal blood vessels but at present much work on treatment of
      arteriovenous malformations and aneurysms is experimental. Both the argon laser
      energy can be transmitted via flexible fibre optic delivery system which can then
      be attached to an operating microscope, slit lamp, endoscope delivery fibre or
      handpiece. The Neodymium-YAG laser is used both for tissue destruction with good
      haemostasis and for the control of normal and abnormal blood vessels. This laser
      produces infrared coherent light at 1060 nm wavelength, which is deeply absorbed
      in the tissues without colour or tissue specificity. Neodymium-YAG laser is
      mostly used in tracheobronchial, gastrointestinal and urologic pathology in the
      treatment of stenoses, granulomas, benign tumours, and for reduction of malignant
      tumours. (ABSTRACT TRUN

PMID- 9611959
TI  - [Primary infection with varicella-zoster virus in risk groups].
AB  - INTRODUCTION: Chickenpox represents the primary form of Varicella-zoster virus
      (VZV) infection and appears most commonly in preschool and school children. The
      clinical course of chickenpox in immunocompetent children is mainly mild and
      complications are rare (1-5). Adults and immunocompromised patients are
      considered to be risk groups for development of serious and even life-threatening
      complications. The most frequent bacterial complications include secondary
      bacterial skin infections, angina, sinusitis, otitis and bronchopneumonia.
      Central nervous system complications, visceral dissemination, pneumonitis and
      myocarditis are the major viral complications (6,7). Acyclovir is approved for
      treatment of chickenpox in risk groups to reduce the frequency of viral
      complications and to treat those ones which have already appeared (7,8). The
      treatment of bacterial complications is based on the examination results of the
      bacterial sensitivity to antibiotics. MATERIAL AND METHODS: In our study patients
      with the diagnosis of chickenpox based on the history of disease, clinical
      features and clinical course and data on intimate contact with individuals
      suffering from chickenpox, were clinically followed-up. Sedimentation rate, blood
      count and urine samples were analyzed. A unique questionnaire was designed to
      follow-up the following data: sex, age, course of the disease, occurrence of
      complications in immunocompetent patients and those belonging to risk groups and
      effects of acyclovir therapy. RESULTS: During a three-year period 48 patients
      with chickenpox treated at the Clinic of Infectious and Dermatovenereology
      Diseases have been observed. 64.6% of them were males and 35.4% were females.
      29.2% were infants under 1 year of age, 29.2% were 2-13 years of age and 41.6%
      were 14-50 years of age. According to the clinical course, patients were divided
      into two groups: the first one included patients who developed complications of
      chickenpox (54.1%), the second one consisted of those without complications
      (45.1%). 72.7% of all complications occurred in patients belonging to risk group
      (14-50 years of age). Among viral complications in risk groups the most common
      were pneumonia (44.4%) and haemorrhagic rash (44.4%), only one patient (11.1%)
      developed a mild, viral meningitis. Bacterial complications were also present in
      risk group as secondary bacterial skin infections (71.4%) and otitis media
      (28.6%). Viral complications were treated successfully by 750 mg intravenous
      acyclovir given 3 times a day, or by 800 mg oral acyclovir given 5 times a day
      during 7-10 days. Adequate antibiotics were used in the treatment of bacterial
      complications. A case of chickenpox associated with the meningitis caused by
      Haemophilus influenzae was also reviewed. DISCUSSION: In this study the majority
      of observed patients had a mild, clinical form of chickenpox that is in
      accordance with the other available clinical data (1-4). Complications developed
      more frequently in the adults and usually were of viral etiology. All patients
      were on time treated with acyclovir and visceral dissemination did not occur in
      any of them. Complications had a favourable evolution and VZV meningitis was
      healed without sequelae. Many authors have written about successful use of
      acyclovir in the treatment of chickenpox. However, acyclovir is not recommended
      to immunocompetent persons without chickenpox viral complications who do not
      belong to risk groups (1,3,4,9-11). CONCLUSION: Our findings lead to the
      conclusion that chickenpox in adults may have an uncertain outcome because of a
      more severe clinical course and susceptibility to complications. In our study
      application of acyclovir in that age group provided good results as for
      prevention and treatment of complications of chickenpox if already manifested.

PMID- 9611960
TI  - Laparoscopic cholecystectomy--analysis of the first 100 operations.
AB  - Laparoscopic cholecystectomy is a surgical method of removing the gallbladder
      through four small incisions on the abdominal wall using laparoscopic technique
      with specially designed equipment and instruments. The method is characterized
      with the following: reduced operative trauma and postoperative pain, shorter
      hospital stay, quicker recovery and better cosmetic effect. This method is in
      surgical practice in the last 10 years, whereas in General Hospital in Senta, in
      the surgical department it was introduced in June 1995. In the period June 16,
      1995-March 1, 1996 one hundred patients underwent laparoscopic cholecystectomy.
      The median age of patients was 48 years; 79% were females and 21% were males.
      There was no operative mortality. Four (4%) mild complications occurred.
      Conversion was performed in only one patient (1%). The average operation time was
      54 minutes, while the postoperative hospital stay was 2.3 days.

PMID- 9611961
TI  - [Epidemiologic characteristics of viral dermatoses--results of a retrospective
      study].
AB  - INTRODUCTION: A great number of skin diseases are caused by viruses (1, 2, 3).
      Virus infections can cause skin diseases due to three mechanisms: direct
      inoculation, systemic infection and local spreading of the internal focus. The
      aim of this study was to determine the characteristics of virus-associated
      dermatoses (VD). MATERIAL AND METHODS: Ambulant patients of policlinical
      department of the Clinic of Infectious and Dermatovenereological Diseases Novi
      Sad were included in this study. Epidemiologic characteristics were analyzed by
      retrospective studying of medical documentation. RESULTS: During a five-year
      period (1991-1995), 1,461 cases of VD were registered or 7.09% of the total
      number of patients examinated in this period (N = 20.596). Majority of the
      observed patients were males (N = 788-53.25%) and female patients were less
      frequent (N = 683-46.75%, table 1). Table 2 shows the age distribution of our
      patients. Most of the patients were in the 20-29 year age group (N = 443 or
      30.32%). The mean age of patients was X = 36.14 years (SD = 19.02). Table 3 shows
      the occupational structure of our patients. The most frequent was the group of
      employed (N = 773 or 50.17%). Table 4 shows the structure of the patients
      according to pathogenic agents. The most frequent was the group of warts and
      condylomata (N = 900 or 61.60%). It is apparent that the number of VD is
      increasing. DISCUSSION: According to collected data, patients with VD make up a
      great group being treated at dermatological clinics. Our findings (7.09%) are
      compatible to the standard results. A relative high mean age of our patients is
      determinated by the fact that the children are managed at the Institute of Health
      Care of Mother and Child Novi Sad (the warts are most frequent in this
      population) or in other dermatological ambulants. There is no evidence that
      actual socio-political events affect the spreading of VD. Most patients belong to
      the urban population making up dominant groups (employed, scholars, pensioners).
      CONCLUSION: The number of patients with VD is increasing. Although from year to
      year the number of diseased increases or decreases, generally speaking there is
      an increasing trend of VD.

PMID- 9611962
TI  - [Brain concussion--a minor craniocerebral injury].
AB  - INTRODUCTION: Brain concussion is a brain dysfunction without any macroscopic
      structural damage, caused by mechanical force. This research paper presents the
      occurrence and basic characteristics of patients with brain concussion without
      skull fracture. The second aim of this paper is to answer questions, related to
      this problem, neurosurgeons are most often asked by doctors of other specialties.
      MATERIAL AND METHODS: Posttraumatic amnesia (patient unable to remember events
      before and/or after injury) was a condition to diagnose the brain concussion. In
      1995 there were 240 patients with brain concussions without skull fracture at the
      Department of Urgent Surgery of our Institute. Eighty of them (33%) have been
      admitted to the Neurosurgical Clinic for observation and/or treatment. In all
      patients with brain concussion the following diagnostic procedure was applied:
      personal history, physical and neurological examination, basic blood tests and
      skull x-rays. CT imaging of the brain is not a routine because of our economic
      and technical circumstances. RESULTS: 240 patients were examined; 67% were males.
      Glasgow coma score (GSC) was 13-15 in all patients, while in nonhospitalized
      patients it was 15 (GSC = 15). 54% of patients were 15-40 years old; 35% were 41
      60 years old and 11% were older than 60 years of age. Average hospitalization
      lasted for 3.48 days. According to the Glasgow outcome scale all patients had a
      good recovery. DISCUSSION: Patients with brain concussion have always amnesia
      with normal neurologic status. Legal and clinical definition of the minor head
      injury are not completely equal. Brain concussion is legally always a minor head
      injury. Patients with organic damage of brain (legally severe injury) can
      clinically look like having minor injury initially or till the end of the
      illness. Risk for brain damage in patients with amnesia is about 3%.
      Posttraumatic amnesia is always established by asking patients to remember events
      and not asking them if they were unconscious. Brain concussion is often
      associated with headache, vegetative or/and psychotic difficulties. Diagnostic
      protocol should comprise at least personal history, physical and neurological
      examination and skull x-ray. Consultation of a neurosurgeon and hospitalization
      are not indicated in all cases. In our series it was done in 33% according to
      indications which are established. In these cases patients should be transported
      with documents describing the type of injury, diagnostic results and treatment
      performed. The therapy is symptomatic. After brain concussion gradual return to
      everyday activities is indicated. Sick leave of 7-10 days is usually sufficient.
      Postconcussion syndrome (headache, vegetative or psychotic disturbances) occurs
      often and may last for a long period of time. CONCLUSION: We tried to describe a
      doctrine for diagnostic and treatment of patients suffering from brain concussion
      most appropriate according to our technical and economical circumstances.

PMID- 9611963
TI  - [Sensitivity of Streptococcus pneumoniae to antimicrobial drugs].
AB  - INTRODUCTION: Streptococcus pneumoniae is the leading cause of community acquired
      pneumonia and a frequent cause of otitis media, sinusitis and meningitis.
      Although most pneumococci remain susceptible to penicillin, relatively less
      susceptible and resistant strains have been recognized with increasing frequency
      throughout the world (1). The aim of this study was to determine whether and to
      what degree pneumococci isolated in our laboratory were resistant to penicillin
      and other frequently used antimicrobial agents. MATERIAL AND METHODS: During the
      period from 1991 to 1995 1139 Streptococcus pneumoniae strains isolated from
      patients with different pneumococcal infections were tested for their
      susceptibility to antimicrobial agents at the Department of Bacteriology and
      Parasitology of the Institute of Public Health in Novi Sad. Antimicrobial agents
      tested included: penicillin, ampicillin, cephalexin, erythromycin,
      sulfamethoxazole-trimethoprim and clindamycin. Susceptibility test was performed
      by using Kirby-Bauer disc diffusion technique on Mueller-Hinton agar supplemented
      with 5% defibrinated bovine blood (5). RESULTS: Susceptibility of Streptococcus
      pneumoniae to seven antimicrobial agents used in the study is shown in Table 2.
      There was a resistance to all antimicrobial agents tested. It was the lowest to
      erythromycin (1.6%) and the highest to sulfamethoxazole+ trimethoprim (67.3%).
      The rate of resistance of penicillin was 3.3%. In Table 3 and 4 we can also see
      that the lowest resistance was to erythromycin, and the highest to
      sulfamethoxazole+trimethoprim, both for isolates from nose and other sources.
      Strains of Streptococcus pneumoniae isolated from nasal swabs were more
      susceptible to penicillin than those isolated from blood, sputum and
      cerebrospinal fluid. DISCUSSION: For many years penicillin has been the mainstay
      of therapy for pneumococcal diseases. Clinical resistance to penicillin was first
      reported in 1960's. Since this early reported, penicillin resistance has been
      encountered with increasing frequency in strains of Streptococcus pneumoniae from
      around the world. In our study resistance to penicillin was low (3.3%). This is
      in accordance with the authors from Italy, Great Britain, USA and Germany (7, 8,
      9, 10). Much higher prevalence of resistant pneumococci we found in the reports
      from Spain, France and Hungary (13, 14, 15, 17). Many of these strains have been
      resistant to multiple drugs and have been isolated from patients with invasive
      infections (meningitis, pneumonia, bacteremia). Percentage of penicillin
      resistant pneumococci isolated from blood, sputum and cerebrospinal fluid in our
      study was relatively low (7.7%), but it was higher than the percentage of
      resistant isolates from nasal swabs (2.0%). These findings are in accordance with
      other reports (20, 21). CONCLUSION: The increasing number of Streptococcus
      pneumoniae isolates resistant to penicillin and other antimicrobial agents
      indicates the need to perform susceptibility testing for every isolated strain in
      order to avoid possible therapeutic failure.

PMID- 9611964
TI  - [Bilateral total hip prosthesis replacement in a single procedure].
AB  - This paper is a case report of a patient with bilateral hip dysplasia, bilateral
      secondary degenerative changes, adduction contracture and serious walking
      difficulties. The patient has undergone one-stage bilateral hip replacement. This
      procedure is advantageous because of fast recovery, fewer complications and
      rehabilitation easier than in the routine operation of two-stage bilateral total
      hip replacement.

PMID- 9611965
TI  - [Prolonged apnea after administration of succinylcholine].
AB  - INTRODUCTION: Succinylcholine is a depolarizing muscle relaxant that has been
      used for five decades in clinical practice. It is decomposed by enzyme
      acetylcholinesterase, which is synthesized in posed by enzyme
      acetylcholinesterase, which is synthesized in the liver. This process lasts a few
      minutes, and is prolonged in the case of hepatic failure of the liver function,
      in normal pregnancy and puerperium, in persons with lack of this enzyme or
      genetic anomaly in its composition. CASE REPORT: The patient, a 31 years old
      woman, was exposed to diagnostic biopsy of endometrium during treatment of
      primary infertility. She received classic short-term general anaesthesia and 1
      mg/kg (50 mg) of succinylcholine. Breathing was completely restored after 90
      minutes. Eventually we found out that in previous three anaesthesias she showed
      the same dysfunction. It was laboratory proven that she had a decrease in
      contents of acetylcholinesterase in plasma (20 mukat/l). The possibility of
      genotype investigation does not exist in our country. The patient was introduced
      in detail with the nature of her disability. DISCUSSION: The activity of enzyme
      acetylcholinesterase depends on functional state of the liver, as well as the
      therapy with some drugs (cyclophosphamide, ecothiopate etc.). For the anaesthetic
      practice the most important is the presence of abnormal acetylcholinesterase. The
      incidence of recessive homozygotes is 1:1500-1:3000 cases in the total population
      and the apnea lasts for 1-2 hours, and sometimes even 4-8 hours. Every apnea over
      15 minutes requires maximal attention of the anesthesiologist. First it is
      necessary to eliminate other possible causes of apnea. The therapy is based on
      oxygenation with 100% O2 blood transfusion or transfusion of fresh frozen plasma
      or preparation of human acetylcholinesterase. CONCLUSION: The case of the patient
      with prolonged postsurgical apnea indicates the decisive significance of
      comprehensive preanaesthetic anamnesis, both in serious surgical and in clinical
      interventions. Since there is no adequate substitution for succinylcholine,
      nowadays it is still in use in clinical practice.

PMID- 9611966
TI  - [Self-measurement and automatic measurement in ambulatory blood pressure
      monitoring].
AB  - INTRODUCTION: There are strictly determined conditions under which blood pressure
      measurement should be done and diagnosis of hypertension made. The first BP
      measurement should be performed on both arms. If there is a difference, controls
      should be made on the side on which the pressure is higher. In older persons the
      Osler manoeuvre should be made in order to exclude pseudohypertension. One should
      be aware that in hospitalized patients the BP is lower due to the bed rest
      itself. SELF-MEASUREMENT OF BLOOD PRESSURE: It seems that erroneous
      interpretation of blood pressure fluctuation and the tendency for self-medication
      by patients are the most important shortcomings of blood pressure self
      monitoring. According to the World Hypertension League instructions, the BP self
      measurement is not recommended for patients obsessed by the disease, neurotic and
      anxious persons, old subjects and in those who are physically handicapped. Since
      the diagnosis of hypertension should be made by the physician in office
      conditions, in our opinion the evolution of the disease and effects of treatment
      should be estimated under the same conditions. BLOOD PRESSURE AMBULATORY
      MONITORING: Ambulatory 24-hour monitoring is of a considerable diagnostic,
      therapeutic and prognostic importance over the casual or self-measurement, but
      one should be familiar with some peculiarrities of this method. Due to the
      adaptation to the device, the values of BP on the first measurement, particularly
      during the first 5 hours are significantly higher than during the subsequent
      measurements. In some subjects the values during the night may be higher due to
      the sleeping disturbances caused by the procedure. Differentiation between
      dippers and non-dippers has some prognostic and therapeutic implications. White
      coat hypertension may be successfully established by the ambulatory measurement.
      There is also a correlation between the BP variations and the myocardial mass.
      The trough:peak ratio may contribute to the estimation of efficiency of a certain
      drug. There are particular indications for ambulatory BP monitoring: the
      differences between the office and home values of BP are considerable; borderline
      hypertension; hypertension without signs of the target-organ damage; transitory
      hypertension of hypotension; syncopal attacks; vague symptoms in hypertensive
      patients; atypical or nocturnal angina; evaluation of the efficiency and duration
      of drug action; for research purposes.

PMID- 9611967
TI  - [Homeopathy].

PMID- 9611968
TI  - [Details and aim of the renaming from the Japan Society of Chest Diseases to the
      Japanese Respiratory Society].

PMID- 9611969
TI  - [Recent advance in alveolar formation].
AB  - Recent technological advance in both molecular biology and morphology contributes
      to develop a research of alveolar formation in pre- and postnatal period.
      Retinoid, which has been known more than 2,000 compounds, has a key role for
      newly alveolar synthesis through various metabolic pathways related Hox gene,
      vitamin A laden fibroblast and collagen-elastin network. It has been shown that
      retinoid is a possible therapeutic regimen not only diffuse lung injury, such as
      bronchopulmonary dysplasia, but also a hopeful new-drug for newly alveolar
      synthesis in severe emphysema.

PMID- 9611970
TI  - [Energy expenditure in patients with pulmonary emphysema].
AB  - We evaluated resting energy expenditure (REE) using canopy mode indirect
      calorimetry in 21 ambulatory, clinically stable outpatients with pulmonary
      emphysema (age: 69.3 +/- 8.4, %IBW: 79.3 +/- 12.5, FEV1: 0.98 +/- 0.36) and
      compared it with that of a 14 age-matched healthy controls (age: 71.1 +/- 6.0,
      %IBW: 94.5 +/- 13.4). We also compared REE in malnourished patients (%IBW < 90;
      73.0 +/- 7.6, N = 14) and normonourished patients (%IBW > or = 90; 92.0 +/- 5.6,
      N = 7). We examined the relation ship between %REE (REE/REEpred. x 100) and
      measurements of lung function tests in 21 emphysema patients using single
      regression analysis. The REE of the patient group was significantly higher than
      that of the control group (%REE; 115.9 +/- 12.0 vs 86.5 +/- 8.7, p < 0.01). The
      REE of the malnourished patient subgroup was significantly higher than that of
      the normonourished patient subgroup (%REE; 121.9 +/- 7.9 vs 109.9 +/- 9.2, p <
      0.01). There were no significant differences in FEV1(L), RV/TLC(%), TLC(pred.%)
      or DLco/VA (pred.%) between the two patient subgroups. The REE of the
      normonourished subgroup was significantly higher than that of control group
      (%REE; 109.1 +/- 9.2 vs 86.5 +/- 8.7, p < 0.01). There were significant relations
      hips among %REE and FEV1, %FVC, FEV1% G, %DLco/VA and RV/TLC (p < .05). These
      findings suggest that elevated REE may have a significant relation ship with
      abnormal lung function, and that elevated REE may be a cause of malnutrition in
      clinically stable patients with pulmonary emphysema.

PMID- 9611971
TI  - [Clinical evaluation of benign asbestos pleurisy].
AB  - Seventeen cases of benign asbestos pleurisy were evaluated clinically. All cases
      were male and almost all cases were more than 60 years-old. Most cases presented
      with chief complaints of chest pain and dyspnea, but 2 cases had no complaints.
      Pleural effusion appeared predominantly in the right side. Six cases had 2 or 3
      episodes of pleural effusion, and 1 case had 5. Ten cases had an occupational
      history of asbestos exposure in shipyards and 5 other cases had a history in
      building construction. Almost all cases had more than 30 years of exposure to
      asbestos and benign asbestos pleurisy appeared after more than 30 years from the
      first exposure to asbestos. Among the patients, 6 cases had diffuse pleural
      thickening and 2 cases had malignancies. Pleural fluid was bloody in 14 of 17
      cases (82%) and all pleural fluid showed an exudate. Lymphocytes represented 70%
      and eosinophils 15% of the cellular population of the pleural fluid. Hyaluronic
      acid in pleural fluid in cases of benign asbestos pleurisy averaged 29.5
      micrograms/ml, which was significantly (p < 0.05) lower than in malignant pleural
      mesothelioma. Leukocytosis in peripheral blood and a high CRP value were uncommon
      in benign asbestos pleurisy.

PMID- 9611972
TI  - [E 4021, a cGMP phosphodiesterase inhibitor, is a selective pulmonary vasodilator
      in chronically hypoxic pulmonary hypertensive rats].
AB  - To test whether a potent cGMP-specific phosphodiesterase inhibitor, E 4021, is a
      selective pulmonary vasodilator in pulmonary hypertension, we studied its acute
      hemodynamic effects in conscious, chronically hypoxic pulmonary hypertensive
      rats. Chronically hypoxic pulmonary hypertension was induced by keeping adult
      Sprague-Dawley rats in a hypobaric chamber for 3 weeks. Two days after
      catheterization. E 4021 was injected intravenously at doses of 3, 10, 30, 100,
      300, and 1,000 micrograms/kg at 10-min intervals. E 4021 caused significant
      decreases in mean pulmonary arterial pressure of 11 +/- 5, 12 +/- 6, and 18 +/-
      5% at doses of 100, 300, and 1,000 micrograms/kg, respectively. In contrast to
      its depressor effect on mean pulmonary arterial pressure, E 4021 decreased mean
      systemic arterial pressure significantly (by 9 +/- 2%) at a dose of 1,000
      micrograms/kg only. Heart rate and cardiac output were unchanged after the
      administration of E 4021. Tissue cGMP-specific phosphodiesterase activity was
      markedly higher in lung than in aorta. These results indicate that E 4021 is a
      relatively selective pulmonary vasodilator in chronically hypoxic pulmonary
      hypertensive rats. We conclude E 4021 may be useful for the treatment of
      pulmonary hypertension.

PMID- 9611973
TI  - [The relationship of carcinoembryonic antigen and neutrophils to pulmonary
      function in healthy smokers].
AB  - We evaluated the relationship of carcinoembryonic antigen (CEA) and neutrophils
      to pulmonary function in healthy smokers. Smokers in whom levels of CEA were
      greater than 5.0 ng/ml (n = 70) and in whom CEA levels were 5.0 ng/ml or less (n
      = 693) had significantly higher mean concentrations of leukocytes and neutrophils
      than non-smokers (n = 651) (leukocytes: 6,883 +/- 1,889/mm3 or 5,581 +/-
      1,457/mm3 vs. 4,507 +/- 1,111/mm3, p < 0.01; neutrophils: 4,389 +/- 1,542/mm3 or
      3,343 +/- 1,164/mm3 vs. 2,700 +/- 884/mm3, p < 0.01). Differences in the ratio of
      vital capacity to the predicted vital capacity (%VC) were not significant. In
      addition, the ratio of forced expiratory volume in one second to forced vital
      capacity (FEV 1.0%) in smokers with CEA levels greater than 5.0 ng/ml was
      decreased compared with smokers with CEA levels of 5.0 ng/ml or less and in non
      smokers (90.2 +/- 8.4% vs. 93.3 +/- 6.7% or 92.9 +/- 6.5%, p < 0.01). These
      results suggest that in healthy smokers high serum CEA levels are related to a
      decreased FEV 1.0%.

PMID- 9611974
TI  - [Effects of uvulopalatopharyngoplasty on patients with obstructive sleep apnea-
      the severity of preoperative tonsillar hypertrophy].
AB  - Predicting outcome following uvulopalatopharyngoplasty (UPPP) in obstructive
      sleep apnea is difficult. We hypothesized that UPPP is effective in obstructive
      sleep apnea patients with severe tonsillar hypertrophy. We examined the
      relationship between the severity of pre-operative tonsillar hypertrophy and the
      effect of UPPP in 38 patients with obstructive sleep apnea (oxygen desaturation
      index (ODI) > or = 20). The patients were classified into three groups according
      to the Mackenzie Classification of tonsillar hypertrophy. Ten patients were
      classified as grade 1 (M1) hypertrophy, i.e. tonsils just visible beyond the
      palatal arch. Five patients had grade 3 (M3) hypertrophy, i.e. tonsils appearing
      to contact each other at the midline. The remaining 23 patients had grade 2 (M2)
      hypertrophy, i.e. intermediate enlargement. We measured the apnea index, ODI, DST
      90, and DST 85 (%time with SaO2 < or = 90% and < or = 85%, respectively) using a
      screening device for sleep apnea (Apnomonitor II, CHEST M. I. Co. Tokyo, Japan)
      before and after UPPP. Following UPPP, the mean ODI decreased significantly in
      all groups: 59 to 9/hr (p < 0.005) in the M3 group, 53 to 27/hr (p < 0.001) in
      the M2 group, and 48 to 33/hr (p < 0.05) in the M1 group. Post-UPPP ODI decreased
      by 83% in M3, 45% in M2, and 28% in M1 patients. Successful UPPP, defined by a
      post-UPPP ODI of less than 20/hr and a greater than 50% decrease in post-UPPP
      ODI, occurred in 80% of M3, 43% of M2, and 10% of M1 patients. We conclude that
      tonsillar hypertrophy can predict a successful response to UPPP in obstructive
      sleep apnea patients.

PMID- 9611975
TI  - [Effect of treatment on health-related quality of life in patients with asthma].
AB  - The aim of the study was to assess the effect of treatment on health-related
      quality of life (HRQoL) in patients with asthma. We used the Japanese version of
      the Living With Asthma Questionnaire (LWAQ) as an asthma-specific HRQoL measure.
      Thirty-four new patients were enrolled and treated according to Guidelines on the
      Management of Asthma by the British Thoracic Society. The LWAQ and spirometry
      were evaluated on the initial visit, and three and six months after treatment.
      The LWAQ score, forced expiratory volume in one second (FEV1), and forced vital
      capacity (FVC) were significantly improved three months after treatment. The
      Japanese version of the LWAQ was reliable. For the first three months, there were
      no correlations between changes in FEV1 or FVC and LWAQ scores (Rs = 0.11-0.25).
      Pulmonary functions could not predict HRQoL well. Therefore, HRQoL should be
      measured directly to assess HRQoL in asthmatics.

PMID- 9611976
TI  - [Relationship between maximum walking distance and frequency of outings in
      patients receiving home oxygen therapy].
AB  - We studied relationships between maximal walking distance (WDmax) and frequency
      of both outing enumerated by the aim of each outing as well as by each outing per
      se in patients receiving home oxygen therapy (n = 109). The results were compared
      with those from members of a seniors' club (n = 434). A questionnaire was used to
      obtain WDmax, defined as the distance a subject could walk without rest on level
      ground. In the questionnaire, WDmax was classified into five groups including 50
      m (the distance between two electric posts), 500 m, 1 km, 1.5 km and more than
      1.5 km. Since few patients could walk 1.5 km or more, they were included into the
      "can walk 1 km or more group". Outing frequency was measured using a 4-week diary
      which showed eight aims of outings including shopping, seeing a doctor, visiting
      friends or relatives, doing a hobby practicing something, participating in a
      seniors' club and neighborhood meetings or events, traveling, work and others.
      The subjects checked the diary each time they went out. True outing frequency was
      defined as the number of outings. If a subject left home to shop and visited a
      friend on the way home, the outing frequency enumerated by aims was two, while
      the true outing frequency was one. The mean and SE (1/4 weeks/one subject) of
      true outing frequency for patients (21.4 +/- 2.2) was significantly less than
      that of seniors' club members (45.6 +/- 1.4). Even in patients with a WDmax of 1
      km or more, the frequency of travel was significantly lower than in seniors' club
      members. Although outing frequencies for shopping, seeing friends or relatives,
      doing a hobby and work were not significantly different between the two groups at
      a WDmax of 1 km or more, the outing frequency for work of patients was
      significantly lower at a WDmax of 500 m, and outing frequencies for the remaining
      three aims became significantly lower at a WDmax of 50 m. We demonstrated that in
      patients receiving home oxygen therapy, outing frequency was limited. A new
      modality is necessary to increase the outing frequency and to improve the quality
      of life for these patients.

PMID- 9611978
TI  - [Therapeutic thoracoscopy for empyema thoracis].
AB  - In empyema thoracis, it is important to reduce the duration of treatment and to
      expand the collapsed lung as fully as possible while managing intrathoracic
      infection. We used thoracoscopy to treat 10 cases of empyema that were not
      completely cured by antibiotics or thoracic drainage. The 8 men and 2 women were
      43-73 years of age. Thoracoscopy was done under general anesthesia except for 2
      pneumonia patients. After inserting two trocars into the thoracic cavity, we
      removed pus, the purulent coat, and fibrinous membrane. Into one unilocular
      cavity, two intrathoracic tubes were inserted via trocarholes. Postoperative
      irrigation of the thoracic cavity was conducted daily through the two tubes. We
      subclassified the fibropurulent stage into three phases, namely, the purulent,
      fibrous, and purulent-capsular. One case required redrainage, but no cases were
      accompanied by severe complications or postoperative death. Patients were
      discharged on post-operative day 33, on average. We found no recurrence or cases
      of recollapsed lung during the study, from 8 months to 4 years and 11 months
      postoperatively.

PMID- 9611977
TI  - [Sleep apnea syndrome in Japan: analysis of pathophysiology and nasal continuous
      positive airway pressure effectiveness].
AB  - Forty eight Japanese sleep apnea syndrome (SAS) patients, whose apnea-hypopnea
      index (AHI) was more than 30 times/hr. from 5 university hospitals (46 males, 2
      females) were enrolled in this study to analyze the characteristics of the
      disorder and the effectiveness of nasal continuous positive airway pressure
      (nCPAP) effectiveness. Although the severity of excessive daytime sleepiness
      (EDS), depressive state, and ventricular premature beats caused by SAS seemed
      milder in Japanese than reported Caucasian patients, the prevalences of
      hypertension and glucose intolerance were quite high: 50 and 30% respectively.
      Treatment with nCPAP for 3 months was completed in 41 of 48 enrollees, a
      compliance rate of 85.4%, which was substantially higher than studies from
      Western countries. nCPAP treatment normalized about 50% of hypertensive patients
      and more than half of glucose intolerant patients. Moreover, EDS, driving
      ability, the severity of arrhythmia, and so forth were all improved with nCPAP.
      We, therefore, conclude that 1) SAS could differ between Japanese Caucasians in
      terms of clinical features resulting from SAS and 2) treatment with nCPAP is
      effective and should be considered as first-line treatment for patients with
      moderate to severe SAS, as reported in Western countries.

PMID- 9611979
TI  - [A case of paraesophageal omental herniation].
AB  - A 48-year-old woman underwent routine chest roentgenography and a mass shadow was
      seen in the posterior mediastinum. CT, MRI and celiac arteriography were
      performed, and paraesophageal omental herniation was diagnosed. Paraesophageal
      omental herniation is uncommon, and there have been no reports cases with
      complications. Therefore, this case is being followed-up carefully.

PMID- 9611980
TI  - [A case of systemic lupus erythematodes with hemosputum and pneumothorax probably
      resulting from pulmonary infarction and pulmonary angitis].
AB  - A 23-year-old man was admitted with fever, bloodysputum and consolidation in the
      bilateral lower lobes. Pulmonary infarction in the potla lower lobes was
      suspected because a lung perfusion scan showed a blood flow defect in the same
      places. Transbronchial biopsy was performed, and pulmonary hemorrhage and
      pulmonary angitis were demonstrated in the left lower lobe. His fever and
      bloodsyputum improved after steroid therapy, suggesting that pulmonary angitis
      may have been responsible for the bloodysputum. Subsequently pneumothorax
      occurred. In this case pulmonary infarction associated with pulmonary angitis may
      have been responsible for the pneumothorax.

PMID- 9611981
TI  - [A case of lung cancer with pericardial effusion without cardiac tamponade].
AB  - Cardiac tamponade as an initial manifestation of primary lung cancer is uncommon.
      All such cases had shown symptoms of cardiac tamponade at the first visit of the
      hospital. We report a case of lung cancer with pericardial effusion without
      cardiac tamponade. Echocardiography, revealed little pericardial effusion and it
      has not increased for 3 months. Pericardiotomy revealed adenocarcinoma and lung
      cancer was confirmed by bronchial biopsy. It is necessary to further examine
      patients with even slight amounts of pericardial effusion.

PMID- 9611983
TI  - [A case of pulmonary infection with mycobacterium xenopi].
AB  - A 42-year-old man with pulmonary disease caused by Mcobacterium xenopi is
      described. He had a history of alcohol use of over 20 years. He was admitted to
      another hospital for evaluation of an abnormal chest shadow. A chest X-ray showed
      a cavitary shadow with infiltration in the right upper lung field. Acid-fast
      organisms were recognized in sputum and M. xenopi was identified by DNA-DNA
      hybridization. Although he had been treated with isoniazid, rifampicin, and
      ethanbutol for 5 years, sputum remained positive on culture and chest X-ray
      findings did not improve. He was later admitted to our hospital for surgery, and
      right upper lobectomy was performed. He has remained well for 18 months since the
      operation. In Japan, cases of the pulmonary infection with M. xenopi are rare.
      Surgical resection is required when chemotherapy is unsuccessful.

PMID- 9611982
TI  - [Percutaneous drainage of a bulla with tuberculous infection in a patient].
AB  - A 63-year-old man complaining of low grade fever and dry cough was admitted to
      our hospital. Chest X-ray showed infiltrative shadows and a bulla with a fluid
      level in the left upper lung field. Bacteriological examination of sputum and
      bronchoalveolar lavage fluid did not yield any diagnostic results. Percutaneous
      aspiration of the bulla under fluoroscopy was performed. Bulla with tuberculous
      infection was considered because a high ADA level was detected in the fluid of
      the bulla. A culture of the bulla fluid was positive for mycobacterium
      tuberculosis (TB), which was sensitive to all anti-mycobacterial drugs. The fluid
      in the bulla gradually increased, and occupied the entire space of the bulla
      three months later. Percutaneous aspiration of the bulla was performed again and
      a fluid smear was positive for TB. It was thought that systemic administration of
      anti-mycobacterial drugs had been ineffective, so percutaneous drainage and
      subsequent injection of anti-mycobacterial drugs into the bulla was performed.
      The fluid in the bulla subsequently disappeared and the bulla shrank gradually.
      Percutaneous drainage of a bulla with tuberculous infection should be considered
      in those who do not respond to medical management.

PMID- 9611984
TI  - [A case of pulmonary eosinophilic granuloma undergoing spontaneous remission].
AB  - A case of pulmonary eosinophilic granuloma that underwent spontaneous remission
      is presented. A 23-year old man presented with dry cough and fever. Chest X-ray
      film revealed diffuse reticulo-nodular infiltrates in the middle and upper lung
      fields. Chest CT and HRCT showed multiple cystic lesions with thick walls and
      small nodules predominantly in the inner zone. Based on radiographic findings,
      pulmonary eosinophilic granuloma was suspected. Bronchoalveolar lavage cell data
      showed lymphocyte and eosinophil alveolitis with no increase of CD 1 lymphocytes.
      The symptoms and radiographic findings improved markedly within 4 months after
      the onset of symptoms without treatment and upon cessation of smoking. Chest CT
      and HRCT showed that the cystic walls were thinner and that the small nodules had
      decreased. Thoracoscopic lung biopsy revealed granulomatous lesions consisting of
      CD 1 and S-100 protein positive histiocytes with infiltration of eosinophils and
      fibrous lesions. Pulmonary eosinophilic granuloma was diagnosed. There has been
      no recurrence for 1 year.

PMID- 9611985
TI  - [A case of thymoma with pleural dissemination which was treated by pleurectomy
      with patient survival without recurrence for more than five years].
AB  - A 46-year-old woman was admitted to our hospital with chest pain. Chest X-ray and
      CT revealed an anterior mediastinal mass as well as several small masses attached
      to the left chest wall. Thymoma was diagnosed by percutaneous biopsy. The serum
      level of anti-acetylcholine receptor antibody was 30.3 pmol/ml. At operation, the
      thymoma was found left in the anterior mediastinum, extending to the upper lobe
      of the lung. There were also numerous tumors of various size in the left parietal
      pleura. Thymectomy, partial resection of the upper lobe of the lung and
      pleurectomy were performed. One month later, she developed myasthenia gravis.
      After a complete remission of myasthenia gravis brought about by anti-choline
      esterase therapy, the patient was treated with irradiation. She has been well for
      more than five years after the operation but her serum anti-acetylcholine
      receptor antibody level is still higher than normal.

PMID- 9611986
TI  - [A case of isoniazid-induced pneumonitis].
AB  - A 55-year-old man was given a diagnosis of pulmonary tuberculosis. He was treated
      with isoniazid (INH), rifampicin (RFP), ethmbutol (EB) and pyrazinamide (PZA).
      After three weeks of treatment, he developed fever, dyspnea and dry cough. A
      chest X-ray taken at that time showed new reticulo-nodular shadows bilaterally
      and right pleural effusion. Ga scintigram showed strong uptake in both lungs.
      Transbronchial lung biopsy revealed alveolitis, suggesting drug-induced
      pneumonitis. Drug lymphocyte stimulation tests for INH, RFP, EB and PZA were
      negative. Because his symptoms were severe, all drugs were discontinued and daily
      predonisolone (30 mg) therapy was started. The symptoms and bilateral reticulo
      nodular shadows soon resolved. The antituberculosis drugs were changed to
      streptomycin and levofloxacin, but these were ineffective. Therefore, EB, RFP and
      PZA, which only rarely induce pneumonitis, were carefully restarted in that
      order. Pneumonitis did not recur and the pulmonary tuberculosis improved. This
      clinical course suggests INH-induced pneumonitis.

PMID- 9611987
TI  - [A case of adenoid cystic carcinoma presenting with stridor and which was treated
      by reversed gamma type stent placement].
AB  - A 66-year-old man was admitted to Saiseikai Suita Hospital with stridor and
      dyspnea. The flow-volume curve showed central airway obstruction pattern.
      Although a P-A chest roentogenogram was normal, chest tomogram demonstrated a
      tumor shadow in the lower portion of the trachea. Chest CT examination
      demonstrated a tumor arising from the posterior wall of the lower portion of the
      trachea and stenosis with wall thickening extending from the lower portion of the
      trachea to both main bronchi. Bronchofiberscopic examination revealed polypoid
      tumors obstructing the lower portion of the tracheal lumen, and biopsy was
      subsequently performed. On the night immediately after the bronchofiberscopic
      examination, the patent suddenly choked, and emergency intubation was performed.
      Adenoid cystic carcinoma was diagnosed on biopsy and we decided to place a spiral
      Z-stent. A reversed gamma-type stent placement was used. The first spiral Z-stent
      extended from the trachea to the right main bronchus and the second spiral Z
      stent was placed in the left main bronchus through the first stent. Following the
      spiral Z-stent placement radiotherapy was performed. Spiral Z-stent placement
      resulted in dilation of the stenotic trachea and both main bronchi.

PMID- 9611988
TI  - [Talc pulmonary granulomatosis caused by intravenous administration of
      methylphenidate].
AB  - A 57-year-old man was admitted with fever and a dry cough in 1985. He had used
      methylphenidate intravenously for 3 years. A chest X-ray film on admission showed
      diffuse micronodular shadows and massive lesions in the lower lung fields
      bilaterally. Pulmonary granulomatosis was diagnosed histologically, but the
      etiology remained unclear. In 1993, the patient was readmitted because of symptom
      exacerbation. The micronodular shadows had extended and the bilateral, massive
      lesions had enlarged. Transbronchial lung biopsy revealed granulomas with
      crystallized foreign bodies. Electron microscopy confirmed that the foreign
      bodies consisted of magnesium and silicon, suggesting talc. Talc granulomatosis
      caused by intravenous administration of methylphenidate was subsequently
      diagnosed. The symptoms improved with conservative treatment, and no signs of
      reexacerbation have appeared.

PMID- 9611989
TI  - [Public nutrition self-defense system in dwelling region just immediately after
      disaster].

PMID- 9611990
TI  - [Impact of health practices on changes in the physical and mental well-being of
      older adults].
AB  - Previous studies on young and middle-aged adults have demonstrated a correlation
      between certain personal health practices and reduced mortality. However, we have
      little knowledge to what extent the findings can be generalized to older adults.
      Our purpose was to investigate the impact of health practices on subsequent
      changes in the physical and mental well-being of the elderly. We used
      longitudinal data of a national representative sample of 2,200 older adults aged
      60 and over at baseline. This six-year prospective study examined the
      associations of six items related to personal health habits--cigarette smoking,
      alcohol consumption, physical exercise, eating breakfast, hours of sleep, and
      relative weight--with subsequent health status change. Not smoking was the only
      health practice that achieved a statistically significant relationship with the
      reduction of future mortality risk. Obesity (20% or more overweight) was a risk
      factor for the subsequent impairment in activities of daily living. Those who
      reported a high frequency of exercise and sleeping 7 or 8 hours per night at
      baseline were less likely to show decreases in their levels of mental well-being.
      These results suggest that not smoking, weight control, physical exercise, and
      sleep patterns may have an important role in maintaining physical and mental well
      being in older adults.

PMID- 9611991
TI  - [Risk factors for circulatory disease in patients on antihypertensive drug
      treatment].
AB  - Proportion of severe cases and mortality in stroke patients has decreased
      steadily in the Minami-Uwa District. The reason for this, has been assumes to be
      that severe hypertensive patients were being detected and treated in early stage
      by the increase in response rate of medical check-up and from improvements in
      health education in cooperation with the Mishou Public Health Center in the towns
      and Villages in the District. However, as there are multiple risk factors for
      hypertensive circulatory disease other then it is necessary to determine what
      factors exist in hypertensive patients. Risk factors for circulatory disease were
      studied in patients using antihypertensive medication at the time of the health
      examination. Of 5,284 residents studied from 1993 to 1994 the prevalence of risk
      factors of atherosclerosis such as obesity, disorders of lipid metabolism and
      glucose intolerance were higher in hypertensive who were normotensive due to
      antihypertensive drugs than in the non-hypertensive residents. Patients with
      resistant hypertension accounted for a third of all the patients using
      antihypersive drugs. Results also showed a relationship between excessive
      reduction in diastolic blood pressure and increased risk of coronary heart
      disease (the J-curve phenomenon) in patients on antihypertensive drug treatment.
      For preventing circulatory disease, it is important to improve the life style of
      hypertensive patients, in areas such as physical activity or dietary habits, and
      develop close cooperation among doctors, public health nurses and nutritionists
      in the regional community, in addition to increasing compliance in maintaining
      antihypertensive treatment. Construction of a network among public health,
      medical care and welfare services is important for prevention and for an improved
      prognosis in circulatory disease.

PMID- 9611992
TI  - [Relationship between dietary calcium and bone mineral density before menopause].
AB  - To study the relationship between dietary calcium intake and bone mineral density
      (BMD) among young Japanese females, we recruited 1298 females under 40 years
      living in Yokohama city for BMD measurement by Computed X-ray densitometer (CXD
      method) and dietary questionnaire. 1. The average of BMD was 2.75 mm/AI and was
      highest in the 35 to 39 year old group. 2. Calcium intake (Ca) and protein intake
      (Protein) were highest in 35 to 39 year old group. 3. BMD, Ca, and Protein were
      significantly higher in those who had regular dietary habits than those with
      irregular habits. 4. Among those who had lower Ca, (less than 600 mg per day),
      the amount of small fish consumed whole was negatively correlated with BMD (p =
      0.035), and those with higher consumption of small fish than average had
      significantly (p = 0.018) lower BMD than those with lower small fish consumption
      adjusting for age and Ca and protein intake. These findings imply a possibility
      that small fish accompanied by higher salt intake may influence BMD adversely in
      this population by an interaction with calcium urinary excretion, which has been
      suggested by experimental and epidemiologic studies. Dietary composition of Ca
      may be important for prevention of osteoporosis.

PMID- 9611993
TI  - [Maximum likelihood estimation of date of infection in an outbreak of diarrhea
      due to contaminated foods assuming lognormal distribution for the incubation
      period].
AB  - This paper proposes a new method for estimating the date of infection in an
      outbreak of diarrhea caused by eating foods contaminated by some sort of
      foodborne pathogens such as Escherichia coli O-157:H7. Simple methods for
      calculating maximum likelihood estimator and confidence interval are proposed
      assuming (1) a common date of infection and (2) the incubation period has a log
      normal distribution. Further, this paper shows that all three methods proposed so
      far for estimating the date of infection under the same assumptions are
      theoretically inappropriate or computationally imprecise. The proposed methods
      are illustrated with data from three outbreaks of Escherichia coli O-157:H7 and
      outbreak due to Escherichia coli O-118:H2 in Japan.

PMID- 9611994
TI  - [An epidemiological survey of sudden infant death syndrome in Tokyo].
AB  - OBJECTIVE: A complete autopsy is essential for an accurate diagnosis of sudden
      infant death syndrome (SIDS), whereas the autopsy rate is low in Japan. This
      study investigated the incidence of SIDS in Tokyo, where the autopsy rate for
      SIDS was the highest in Japan. METHODS: We selected death certificates of infants
      aged less than 2 years during 1990 to 1992 in Tokyo, whose cause of death was
      suspected to be SIDS, and classified those possibilities of SIDS according to
      death descriptions. RESULTS: The incidences of SIDS by strict definition and
      broad definition were 0.23 and 0.32 per 1,000 live births, respectively. Not a
      few death certificates described causes of death and death scene at some length.
      If including cases of suspected SIDS, the incidence came to 0.61 per 1,000 live
      births. The mortality risk of SIDS was significantly higher in infants with male
      gender and households classified by employment status as "other". Because the
      medical examiner system functioned only in the central urban area, most SIDS
      cases were diagnosed at autopsies in the urban area, whereas few cases were
      autopsied in the surrounding area. Compared to the urban area, the incidence of
      SIDS was significantly lower in the surrounding areas with low autopsy rates and
      with many death certificates of ambiguous death description. CONCLUSIONS:
      Ambiguous description of the death scene and low autopsy rate may cause under
      diagnosis of SIDS. Establishment of a nationwide medicolegal autopsy system and
      examination of the death scene is necessary to diagnose SIDS accurately.

PMID- 9611996
TI  - [The relationship between hepatitis C virus-induced hepatocellular injury and
      life style].

PMID- 9611995
TI  - [Internalized norms and social norms relating to negative health behaviors. The
      relationship of sociodemographic characteristics and reference groups].
AB  - So-called "negative health behaviors" (e.g. smoking, excessive eating/drinking),
      which are related to morbidity and mortality, are generally well known to the
      public. However there are many who undertake negative health behaviors despite
      knowing of their negative health effects. Using a mail survey of subjects aged 25
      to 54, we examined reasons and justifications for engaging in negative health
      behaviors and their related factors from the lay person's perspective. Concerning
      the reasons for negative health behaviors, we hypothesized seven concepts (work
      priority, group harmony priority, the contribution to relaxation, tools for
      communication, prior orientation focused on the present, individualistic
      priority, and appearance), and devised multiple questions for each concept. The
      results are as follows. 1. Compared to females, males tended to support of the
      five concepts about the internalized norms concerned with negative health
      behaviors (e.g. the tendency of each individual to approve or disapprove of the
      reasons for negative health behaviors). In females, the younger generation and
      those that were married expressed more support than the older and the unmarried.
      There were differences in males according to occupation. 2. Concerning which
      reference groups had the largest influence on the social norms concerned with
      negative health behaviors (e.g. the perceptions as to what degree a group regards
      the reasons about negative health behaviors as desirable), most perceived that
      the "office" and "friends" groups would be more supportive of reasons for
      negative health behaviors than the "family" groups. 3. The health behaviors,
      which correlated with the internalized norms or the social norms concerned with
      negative health behaviors, were eating breakfast, smoking, and drinking
      (frequency and amount). In particular, drinking behavior was influenced most by
      the internalized norms and the social norms.

PMID- 9611997
TI  - [Personal risk index of chronic respiratory symptoms].

PMID- 9611998
TI  - Current trends in biocompatibility testing.
AB  - Biocompatibility remains the central theme for biomaterials applications in
      medicine. It is generally accepted that this term means not only absence of a
      cytotoxic effect but also positive effects in the sense of biofunctionality, i.e.
      promotion of biological processes which further the intended aim of the
      application of a biomaterial. The national and international standards for
      testing regimes represent a lowest common denominator for such applications and
      do not necessarily ensure that optimal function will be achieved. The authors'
      thesis is that biocompatibility testing has scope for extensive development with
      respect to biofunctionality. The present paper reviews current trends in the in
      vitro aspects of biocompatibility testing. As well as a critical appraisal of the
      recent literature, future trends are also stressed, which the authors regard as
      essential for a meaningful integration of a modern biological approach into new
      developments in the material sciences. These include the application of modern
      techniques of cell and molecular biology, the concepts of tissue remodelling,
      hybrid organ development and encapsulated cell technology.

PMID- 9612000
TI  - Composite hydrogels for implants.
AB  - Hydrophilic composite structures are designed to mimic the transport and
      mechanical properties of natural soft tissue such as tendons, ligaments and
      intervertebral discs. Mechanical and viscoelastic behaviour of a soft composite
      material based on a hydrogel matrix reinforced with bundles of polyethylene
      therephthalate (PET) fibres is analysed. The typical J-shaped stress-strain
      behaviour, displayed by natural tendons and ligaments, is reproduced. The
      mechanical characteristics, such as the extent of the 'toe-in region' and the
      elastic modulus in the linear region, can be controlled by varying the winding
      angle of the fibres and the matrix composition. Dynamic mechanical analysis
      showed the dual behaviour of the composite systems due to the progressive
      contribution of the PET fibres. Different poly(2
      hydroxyethylmethacrylate)/polycaprolactone (PHEMA/PCL) semi-interpenetrating
      polymer networks (IPNs) hydrogel composite systems reinforced with PET fibres
      have been investigated for potential use as intervertebral disc prostheses.
      Compression properties have been evaluated by static and dynamic tests. Uniaxial
      compression tests on the swollen samples showed an increase of the modulus and
      maximum stress with increasing content of PCL and PET fibres. Creep behaviour is
      also dependent on the hydrogel composition. The composite PHEMA/PCL hydrogels
      showed compression properties similar to those expressed by canine intervertebral
      discs in different spinal locations.

PMID- 9611999
TI  - Fibroblast responses to mechanical forces.
AB  - The repair and maintenance of connective tissues is performed predominately by a
      mesenchymal cell known as a fibroblast. The activity of this cell is regulated,
      in part, by changes in the mechanical environment in which it resides. The
      authors have addressed some of the questions related to the fibroblast and how it
      responds to mechanical stimulation. An in vitro model, the 'culture force
      monitor', and its derivative, the tensioning culture force monitor have been
      developed enabling quantitative investigations to be performed on fibroblasts in
      a collagen lattice. Results have shown that a fibroblast can generate a force of
      approximately 10(-10) N, as a result of change in cell shape and attachment,
      while in a three-dimensional collagen lattice. Application of a physiologically
      similar mechanical load has shown that fibroblasts have the ability to maintain a
      tensional homeostasis of approximately 40-60 x 10(-5) N per million cells, change
      cellular morphology in a predictable manner and biochemically modify their
      resident environment.

PMID- 9612003
TI  - Glass-ionomers in medicine and dentistry.
AB  - This paper describes the current uses and future prospects for glass-ionomer
      cements in dentistry and medicine. Glass-ionomers divide into two chemical types,
      one is known as self-hardening and sets entirely by a neutralization reaction to
      give relatively brittle materials, the other is known as resin-modified and sets
      partly by polymerization and partly by neutralization to give slightly tougher
      materials. Compared with the self-hardening cements, these latter materials have
      improved aesthetics and easier clinical handling. Both types bond well to enamel
      and dentine, and release clinically useful amounts of fluoride. They have been
      used in a variety of applications in dentistry, including as liners/bases, luting
      cements for stainless steel crowns, and in various restorative procedures for
      both permanent and primary teeth. The resin-modified glass-ionomers are
      particularly promising for these latter uses, though it is too soon to be sure
      how durable they will prove to be over the longer term. Self-hardened glass
      ionomers have been shown to have much better biocompatibility than resin-modified
      glass-ionomers in a variety of situations and consequently they have been used
      for various non-dental applications, such as ear, nose and throat surgery and
      craniofacial reconstruction.

PMID- 9612006
TI  - [Why physicians should read (also) nonmedical books].

PMID- 9612001
TI  - Bioabsorbable polymers: materials technology and surgical applications.
AB  - Biostable and bioabsorbable biomaterials are used to manufacture implants for
      supporting, replacement, augmentation and guiding of growth of tissues.
      Bioabsorbable implants are a better choice for applications where only the
      temporary presence of the implant is needed. Because of bioabsorption of such
      implants, there is no need for a removal operation after healing of the tissue
      and the risks of implant related, long-term complications are eliminated or
      strongly reduced. Reinforcing of bioabsorbable materials is necessary in order to
      develop strong and safe, small implants for fixation of bone fractures and
      connective tissue damage. Self-reinforced bioabsorbable polymeric implants have
      been used so far extensively in the treatment of traumas of the musculoskeletal
      system.

PMID- 9612002
TI  - Bioactive bone cements.
AB  - Poly(methylmethacrylate) (PMMA) bone cement, used to fix implants into the bone,
      produces good surgical results if used correctly. However, prostheses do
      eventually become loose and the breakdown of the cement mantle is a factor in
      this failure. Limitations of PMMA cement, which lead to problems with the
      fixation of the implant, include its mechanical characteristics and its influence
      upon surrounding bone, associated with the polymerization reaction. A bioactive
      bone cement is particularly designed to produce a better interface between the
      cement and bone. However, an improvement in mechanical properties, especially
      fatigue, creep and fracture toughness, are an added necessary requirement to
      increase the lifetime of a cemented implant. The development of a bioactive
      cement has been conducted mainly in two ways; firstly, to improve existing PMMA
      cement by the addition of various bioactive agents and secondly, to design an
      alternative matrix for the bioactive material to be combined with. The most
      promising investigations which have been conducted, along with their relative
      benefits and drawbacks, are discussed.

PMID- 9612004
TI  - Mechanical properties of bioactive glasses, glass-ceramics and composites.
AB  - The application of bioactive glass and glass-ceramics has been widely documented
      over the past twenty years but the high modulus and low fracture toughness has
      made them less applicable for clinical, load bearing, applications. The
      development of non-resorbable polyethylene and polysulphone matrices for these
      materials has improved the mechanical properties. However, the primary concern of
      whether the bioactivity of the composites is reduced is still unresolved. The
      more recent development of resorbable carrier systems, dextran and collagen, for
      bioactive glasses does not introduce such problems, hence making this form of
      composite suitable for novel soft tissue applications. The development of a
      simple quality index has enabled some of the materials described within this
      paper to be ranked by their ability to replace bone, thus enabling possible new
      research directions to be emphasized.

PMID- 9612005
TI  - Calcium phosphate coatings for medical implants.
AB  - In surgical disciplines where bone has to be repaired, augmented or improved,
      bone substitutes are essential. Although bone banks, such as Eurotransplant, are
      founded to supply such substitutes, natural bone is not always adequate. For
      example, frequently these so-called bone grafts resorb after implantation (1).
      Further, they cannot be used for joint and tooth replacement, and recently
      worries have been raised about the transfer of infectious diseases. Therefore,
      interest has dramatically increased in the use of synthetic materials for
      replacement of lost or damaged bone tissue. The generic name of these tissue
      alternatives is biomaterials. A special class of these biomaterials is composed
      of metallic devices with coatings to improve bone bonding. These specialized
      coatings used to improve the metallic implant are the topic of this paper.

PMID- 9612008
TI  - [Obesity and hypertension: the role of magnesium].
AB  - We focus on the recent "ionic hypothesis", in which an alteration of ionic
      metabolism represents a peculiar event in the pathogenesis of obesity and
      hypertension. We report the results from our original studies in which we
      evaluated intraplatelet magnesium levels. In a study on normotensive and
      hypertensive patients with non insulin-dependent diabetes mellitus and healthy
      control subjects, we showed a common reduction of plasma, erythrocyte and
      platelet magnesium levels in both normotensive and hypertensive diabetics with
      respect to control. Anyway, hypertensive diabetics showed a greater reduction of
      intraplatelet magnesium concentrations when compared to normotensive diabetics.
      Using the same technique, we found reduced erythrocyte and platelet magnesium
      concentrations in patients with essential hypertension with respect to the
      control group. In a successive study, we found, in the group of normotensive
      obese, that erythrocyte and platelet magnesium levels were significantly lower
      than those of the control group, while in hypertensive obese patients a reduction
      of plasma magnesium levels has been also detected. In conclusion, in these
      studies has been confirmed the existence of a reduction of the intracellular
      magnesium concentrations, which is common in hypertensive and obese patients.

PMID- 9612009
TI  - [Efficacy of topical azelastine in the treatment of allergic rhinitis caused by
      Parietaria officinalis].
AB  - We have evaluated the efficacy of azelastine, a new long acting antihistamine, in
      the topic treatment of seasonal allergic rhinitis to Parietaria officinalis.
      Forty five patients have been considered, 20 males and 25 females, mean age 28.5
      years, suffering from seasonal rhinitis to Parietaria officinalis for at least 4
      years. Azelastine was administered twice a day for 4 weeks in the pollen season.
      On a daily diary-card, patients had to record the severity of the symptoms
      considered: runny nose, sneeze, itching nose, nasal obstruction, following an
      arbitrary score from 0 to 3. At the end of the study, patients obtained a
      significant improvement of the symptoms considered without the addition of any
      other topical or systemic therapy. No side effects have been reported. Therefore
      azelastine is an effective drug in the treatment of seasonal allergic rhinitis to
      Parietaria officinalis.

PMID- 9612007
TI  - [Latent thyroid diseases in obesity].
AB  - We have investigated 2672 obese subjects (2324 females and 348 males); of these,
      the following two groups were considered: obese subjects with or without thyroid
      disease. Subjects were stratified according to age, sex, and BMI. The prevalence
      of thyroid disease was correlated to age, sex and BMI increased body weight. Our
      data showed that 22% of patients affected by essential obesity and not resident
      in area of iodine deficiency is affected by thyroid diseases which are not
      diagnosed (18%). In the obese subjects, presence of goiter is more frequent than
      in the normal weight subjects and affects mainly adult males. Chronic thyroiditis
      is typical of females (9:1 female:male ratio) with no difference between normo
      and overweight subjects. Prevalence of single nodule in the obese is similar to
      the normal weight subjects, it is more frequent in adults and in subjects with
      medium size obesity. However, occurrence of carcinoma (8%) in single nodules
      appears higher in the overweight (5-6%) as compared to the normal weight
      subjects.

PMID- 9612010
TI  - [Hematological changes in hyperthyroidism. A case report].
AB  - A case of microcytic anemia, leukopenia (with lymphocytic reduction prevalence)
      and light thrombocytopenia is reported. The case occurred to a 63-year old
      diabetic woman suffering from Basedow's disease. The thyropathy was diagnosed
      first and the patient did not undergo to any previous treatment with antithyroid
      agents. The bone marrow aspiration only showed slight dyserythropoietic notes,
      with slight reduction of myeloid-erythroid ratio. The blood cell indexes rapidly
      normalized as soon as euthyroidism was achieved by radioiodine therapy (I131,
      4mCi), and this led to think there was a relationship between thyropathy and
      blood modifications. The patient was subsequently treated with levothyroxine
      because of the occurrence of a iatrogenic hypothyroidism. Two years later, during
      a follow-up, all the hematologic parameters were normal, as well as the serum
      concentration of thyroid hormones and TSH (during opotherapy). We report the
      hematologic alterations most frequently observed in hyperthyroidism and underline
      the peculiarity of this case as it shows the simultaneous alterations of
      different cellular lines in the same patient.

PMID- 9612012
TI  - [Arterial hypertension and the salt war].

PMID- 9612011
TI  - Endocrine effects of two pineal hormones other than melatonin in healthy
      volunteers: 5-methoxytryptophol and 5-methoxytryptamine.

PMID- 9612013
TI  - [From Chronos to Chaos: from the determinism of circadian rhythm of arterial
      pressure to the undeterminism of hypertensive crises].
AB  - This paper delineates the scientific though about the disorder (chaos) in dynamic
      phenomena. The discussion shows how the periodic functions, which are
      intrinsically deterministic, can break down into chaotic patterns, either global
      or catastrophic, because of their "dependence on the limits in the oscillatory
      modulation" (cycle stress limits). The argumentations demonstrate that order and
      disorder, chronos and chaos, are intrinsic aspects of dynamic phenomena. The text
      presents the fractal mathematics for analysing nonlinear events. The fractal
      interpolation is proposed for predicting the potential risk of hypertensive
      crisis using the noninvasive ambulatory blood pressure monitoring.

PMID- 9612015
TI  - [Nifurtimox as a prophylactic drug to prevent reactivation in chronic chagasic
      patients treated with corticoid for associated diseases].
AB  - Patients in the chronic phase of Chagas' disease and receiving corticoid because
      of concommitant diseases were treated with nifurtimox. We proved in another paper
      that in the chronic phase of Chagas' disease corticoid use is associated with
      increased parasitemia, as evaluated by xenodiagnosis. In this study nifurtimox
      use prevented this increase, and we suggest that in immunocompromised patients
      with chronic Chagas' disease the use of this drug could be useful.

PMID- 9612016
TI  - [Adrenal gland morphological alterations in the acquired immunodeficiency
      syndrome].
AB  - In the acquired immunodeficiency syndrome (AIDS), the adrenal glands are subject
      to opportunistic infections, neoplasm or direct cytopathic effect by HIV. It is
      know that the incidence and type of adrenal involvement vary according to the
      patient's place of origin. In this paper we evaluate adrenal involvement in
      fourteen patients that died from AIDS in the University Hospital of Uberaba,
      Brazil. The group studied was comprised of thirteen males and thirteen whites.
      The age was 29.9 +/- 7.8 years, and the body mass index was 19.0 +/- 4.1 kg/m2.
      Adrenal specimens obtained from autopsies were analyzed by light microscopy.
      Inflammation was found in 100% of the cases and the etiologic agent(s) was (were)
      identified in eight (58.1%) patients. Cytomegalovirus was identified in seven
      cases, Cryptococcus sp and Herpes simplex in two and Histoplasma sp in one case,
      these pathologic findings were similar to literature. We also found parenchymal
      calcification and adrenal central vein phlebitis in one case each. Injury was
      found in some cases without identified infections agent. This fact could be due
      to the direct cytopathic effect by HIV, or due to toxicity of drug therapy used
      during treatment of AIDS and opportunistic infections.

PMID- 9612017
TI  - [Multiple antibiotic resistance mediated by R plasmid in Shigella flexneri
      strains isolated in the northeast of Brazil].
AB  - In Shigella strains were studied the molecular mechanism that mediated the
      multiply antibiotic-resistance. Twenty-six strains of Shigella flexneri were
      utilised in this investigation. These strains were submitted to disk diffusion
      test, mating experiments and plasmid isolation. In relation to antibiotics
      resistance standard it was observed that all Shigella flexneri strains were
      resistant to at least, three antibiotics tested. From twenty-six Shigella
      flexneri strains donors submitted to conjugation process, 34.6% (nine strains)
      resulted in variable frequency of transconjugants. From strains that conjugated,
      100%, transferred the resistance factor acquainted with ampicillin. Being that,
      in all transconjugants which were observed, just one plasmid with 23.1 Kb was
      evidenced. This plasmid found in all strains was characterised as the cause of
      resistance to ampicillin.

PMID- 9612018
TI  - Analysis of Toxoplasma gondii antigens with sera from toxoplasmosis patients.
AB  - Some proteins of the Toxoplasma gondii are recognized by IgG, IgM and IgA
      antibodies in patients with acute and chronic toxoplasmosis, depending on the
      strain and stage of the Toxoplasma. Sixty-nine sera from immunocompetent
      individuals were studied through the Western-Blot Test: 20 has an acute
      infection, 29 has a chronic toxoplasmosis infection and 20 were healthy
      (seronegatives). The protein analysis revealed by IgG and IgM antibodies were
      performed through the immunoplot method in order to know their recognition
      frequency (f) and be valued as infection markers. In the acute phase, the IgM
      antibodies showed a recognition frequency (f = 0.60) for the 60 kDa protein, and
      in the chronic phase the IgG antibodies showed a recognition frequency (f = 0.68)
      for the 12 kDa protein. Seronegatives revealed no type of band. The protein of 12
      kDa can be a diagnostic marker of the chronic phase while protein 60 kDa of the
      acute phase of toxoplasmosis.

PMID- 9612014
TI  - [Leptin: adipocyte hormone].
AB  - The authors reviewed the most recent literature on leptin, a protein produced by
      adipocytes which exerts its action on hypothalamus, modifying eating behavior and
      inhibiting the lust for food consumption. This one appeared to be the main, if
      not the only, physiologic action of leptin. Later leptin has been acknowledged a
      major role in the homeostasis. The regulation of the synthesis, and the
      mechanisms by which the protein modulates both food intake and energetic balance
      have been evaluated, and the hypotheses on the regulatory function exerted by
      leptin on the homeostasis, by acting on neuroendocrine system, on sexual maturity
      and fertility, on the sympathetic nervous system, on hemopoiesis and
      hydroelectrolytic balance have been discussed, some of which being already
      supported by experimental evidences.

PMID- 9612020
TI  - Angiostrongylus costaricensis and the intermediate hosts: observations on
      elimination of L3 in the mucus and inoculation of L1 through the tegument of
      mollucs.
AB  - Human accidental infection with Angiostrongylus costaricensis may result in
      abdominal disease of varied severity. Slugs from the Veronicellidae family are
      the main intermediate hosts for this parasitic nematode of rodents. Phyllocaulis
      variegatus, Phyllocaulis soleiformis and Phyllocaulis boraceiensis were
      experimentally infected to describe the kinetics of L3 elimination in the mucus
      secretions of those veronicelid species. A maximum of 2 L3/g/day was found in the
      mucus, while the number of L3 isolated from the fibromuscular tissues varied from
      14 to 448. Productive infection was established by inoculations in the hyponotum
      or in the body cavity, through the tegument. Intra-cavity injection is a less
      complex procedure and permits a better control of inocula. A preliminary trial to
      titrate the infective dosis for P. variegatus indicated that inocula should range
      between 1000 and 5000 L1. The data also confirmed the importance of P. variegatus
      as an intermediate host of A. costaricensis.

PMID- 9612019
TI  - [Comparative study of American tegumentary leishmaniasis between childhood and
      teenagers from the endemic areas Buriticupu, Maranhao and Corte de Pedra, Bahia,
      Brazil].
AB  - A comparative study on children aged 0-15 years, with American tegumentary
      leishmaniasis (ATL), in the endemic regions of Buriticupu (MA) and Corte de Pedra
      (BA), whereby 214 cases were detected between 1982 and 1993, 78 (36.4%) of them
      originated from Corte de Pedra and 136 (63.6%) from Buriticupu. In Corte de
      Pedra, most cases were observed in patients aged between 0-5 years. Twenty nine
      (37.2%) cases; 62% of those were male. In the Buriticupu region, 88 (64.7%) cases
      occurred in patients of 11-15 years of age, where in 73.8% consisted of male. In
      both researched regions, brunetts were predominant, with a ratio of 65.4% in
      Corte de Pedra and 75% in Buriticupu. Twenty six (33.3%) children in the village
      of Corte de Pedra were farmers, predominantly male (57.7%), generating
      statistical significance (chi 2 = 11.21). Twenty one (80.8%) farmers were aged 11
      15 years. Thirty seven and a half per cent of the children from Buriticupu were
      students, however, 41 (30.2%) were farmers, representing 39 (44.3%) cases; all of
      them male. Both in Buriticupu and Corte de Pedra, the unique wound was
      predominant, corresponding to 57.7% and 53.7%, respectively. The wounding time
      stood out from one to three months, with 45 (69.2%) cases in Corte de Pedra and
      73 (61%) in Buriticupu (chi 2 = 11.82). As to the wound locations, it has been
      observed that they were most constantly present on the lower limbs, with 77.2% in
      Corte de Pedra and 58.9% in Buriticupu (chi 2 = 27.9). The cutaneous case mostly
      found in Corte de Pedra was the ulcerous one (91%). IDRM was positive in 61
      (78.2%) children originated from Corte de Pedra, wherein no statistical
      difference was detected between age ratio and positivity of the test (chi 2 =
      0.0669).

PMID- 9612025
TI  - [New version of the uniform requirements for manuscripts submitted to biomedical
      journal].

PMID- 9612026
TI  - [Books on anesthesiology and resuscitation published in Spain. An approach to
      their study].
AB  - INTRODUCTION: Few authors have examined the publication of medical books. Our aim
      was to analyze the nature of books published in Spain on anesthesiology and
      recovery. MATERIAL AND METHODS: Books listed by the Spanish ISBN agency were
      selected if they included anestesi* or reanima* in any field. Duplicates were
      removed. Multiple editions or references were considered single books, with data
      for the oldest edition entered into analysis. Multiple volume collections were
      grouped as complete works. Data analyzed for each book were year of publication,
      language (of publication and the original), subject (according to ISBN
      classification) and place of publication. Nine subject classifications were
      applied: general, recovery, anesthetic techniques, pharmacology,
      obstetrics/gynecology, pediatrics, veterinary anesthesia, dental anesthesia and
      miscellaneous. RESULTS: We analyzed 216 books. Years that saw publication of the
      greatest number of books were 1988 (17), 1993 (16) and 1979 (15), and the five
      year period in which the most books were published was 1985 to 1989 (48 books,
      22.2%). Most books (114, 52.8%) were originally written in English, Spanish being
      the second most common original language (58, 26.8%). All books were published in
      Spanish. The Spanish ISBN classification system identified 11 categories: general
      diseases/clinical medicine/therapy (161, 74.5%); drugs/pharmacology/physical
      therapy/toxicology (20, 9.3%); gynecology/obstetrics (9, 4.2%), veterinary
      medicine (9, 4.2%) and medicine (8, 3.7%). Classification by specific subjects
      showed a predominance of monographs or treatises on general aspects (42, 19.4%)
      followed by books on recovery (37, 17.1%), anesthetic techniques (25, 11.6%) and
      pharmacology (17, 7.9%). Most books were published in Barcelona (142, 65.7%),
      Madrid (36, 16.7%) or Saragossa (10, 4.6%). CONCLUSIONS: Spanish publication of
      books on anesthesiology and recovery has increased in recent years. Most books
      are translations usually from English. Spanish ISBN agency data, although it has
      limitations, can be useful for locating books published in Spain on
      anesthesiology and recovery. It would be useful to introduce keywords into the
      ISBN data base so that books on specific subjects could be classified and
      retrieved.

PMID- 9612024
TI  - [The using of hollow bricks as a shelter for adaptation of wild rodents' colonies
      in captivity].
AB  - Difficulties for adaptation of wild rodents' colonies in the laboratory may
      hamper experimental studies. We describe the use of a hollow brick inside cages,
      to provide shelter and reduce stress of the animals. It facilitates the cleaning
      of cages, since the animals stay inside the brick while they are transferred to a
      new cage. This method was applied in a trial for adaptation of Oryzomys nigripes
      in captivity. Despite transportation for more than 1500 km, mortality was zero in
      the group of 62 rodents and the colony expanded immediately. A hollow brick is a
      cheap and widespread available material for improving adaptation of wild rodents
      to captivity.

PMID- 9612022
TI  - [Indeterminate form of Chagas disease: considerations about diagnosis and
      prognosis].
AB  - The indeterminate form of Chagas' disease is defined by the absence of clinical,
      radiological and electrocardiographic manifestations of cardiac or digestive
      involvement in Trypanosoma cruzi chronic infected persons. When submitted to
      advanced cardiovascular tests, these patients may present significant
      abnormalities. However, the indeterminate form concept was reaffirmed as valid,
      since diagnostic criteria are simple and prognosis is benignant. In clinical
      practice, diagnostic difficulties are frequent, related to subjectivity and
      uncertain meaning of clinical, electrocardiographic and radiological findings.
      Moreover, indeterminate form prognosis is not equally good: after five to 10
      years, a third of patients will have cardiopathy. Sudden death, a rare
      complication, may be the first manifestation of Chagas' disease. It is necessary
      to reappraise indeterminate form concept, redefining diagnostic criteria and
      therapeutic management. Clinical and noninvasive evaluation may allow individual
      risk stratification; therapeutic interventions may be beneficial in high risk
      groups. Since etiologic treatment may prevent cardiopathy, its role in
      indeterminate form management must be reassessed.

PMID- 9612021
TI  - [Evolutive aspects of post-transfusion hepatitis C. Review of 175 cases].
AB  - Hepatitis C virus is the main agent responsible for post-transfusion hepatitis.
      Progression to chronic hepatitis, cirrhosis and hepatocellular carcinoma is very
      common. The aim of this study was to evaluate the frequency, timing and factors
      related to progression of hepatitis C. One hundred seventy five patients with
      chronic post-transfusion hepatitis C were grouped in a cirrhosis group (n = 92)
      and a non-cirrhosis group (n = 83). The medium time of development to cirrhosis
      was 11 +/- 6 years. Patients with cirrhosis were older at the time they received
      transfusion, used more alcohol and had longer times of evolution. The prognosis
      was worse in the cirrhosis group with a mortality rate of 28.4% and 9.1% of
      evolution towards hepatocellular carcinoma, comparing with 5.5% and 0% in the non
      cirrhosis group respectively. It is shown that post-transfusion hepatitis C is
      slowly developing progressive disease which progress is much more rapidly in
      elderly patients and patients with others factors of liver damage.

PMID- 9612028
TI  - [Requirements for uniformity of manuscripts presented for publication in
      biomedical journals. International Committee of Medical Journal Editors].

PMID- 9612023
TI  - [Miliary tuberculosis - report of a case].
AB  - This is a case report of generalized miliary tuberculous infection in a 80-year
      old white male without the acquired immunodeficiency syndrome, whose death was
      caused by progressive hematogenous seeding similar to those cases of
      preantibiotic era. The importance of autopsy studies to uncover silent or protean
      infections specially in cases of cryptic or chronic hematogenous miliary
      tuberculosis, is emphasized.

PMID- 9612030
TI  - [Perforation and entrapment of an intra-aortic balloon: a complication related to
      the duration of implantation].
AB  - A 69-year-old man was admitted to the Intensive Care Recovery Unit after heart
      surgery, carrying an intra balloon counterpulsation (IABCP) device inserted
      percutaneously days before surgery to provide hemodynamic support and which was
      still required after surgery. Fifteen days after insertion, blood was observed in
      the safety chamber. Surgical removal of the catheter was required when attempts
      to remove it manually failed. The balloon was seen to be perforated and clotted
      blood was found inside. We believe that long-term maintenance of IABCP carries
      high risk of perforation and entry of blood, which will clot, as well as of
      catheter entrapment unless removal is prompt.

PMID- 9612029
TI  - [The incidence of intraoperative conciousness in emergency surgery and its
      possible relation to the post-traumatic stress syndrome. Presentation of three
      cases].
AB  - Intraoperative awakening and recall of specific events is a rare complication
      (0.2 to 1.3%) of surgery. The possibility of developing serious psychiatric
      complications, such as posttraumatic stress disorder (PTSD) makes the prevention
      and detection of intraoperative awareness a subject of special interest. We
      describe our experience with three patients in whom awareness was detected during
      emergency surgery under general anesthesia. We conducted two structured
      interviews with the patients three months after surgery in order to detect the
      possible development of psychiatric complications. One patient suffered insomnia
      and reexperience of the event during the first two weeks after surgery.
      Improvement was spontaneous. None of the patients suffered PTSD. Efforts to
      decrease the incidence of episodes of intraoperative awakening with specific
      recall must be based on clinical observation and exhaustive monitoring of the
      patient, including anesthetic gases, given that no ideal method of monitoring
      depth of anesthesia exists. Cases should be detected in the first few days after
      surgery by means of a specific test. Likewise, possible causes for the episode
      should be explained to the patient, who should be followed for six months so that
      early diagnosis of PTSD or other psychiatric complications can be made.

PMID- 9612027
TI  - [The effect of isoflurane on coronary autoregulation in hypothermia].
AB  - OBJECTIVES: To analyze the effect of isoflurane on myocardial metabolism and
      coronary hemodynamics during the reheating phase after heart surgery. PATIENTS
      AND METHODS: Sixteen patients (12 women and 4 men), with cardiac output greater
      than 0.5 undergoing aortic and/or mitral valve surgery, were studied
      prospectively. A retrograde thermodilution catheter was placed in the heart and a
      Swan-Ganz catheter was inserted in the pulmonary artery to determine coronary
      blood flow and pulmonary wedge pressure, respectively, as well as myocardial and
      systemic parameters. After surgery, and with hemodynamic variables stable and
      rectal temperature at 34 +/- 0.5 degrees C, 0.4% isoflurane was administered at
      the end of expiration. Variables were recorded before administering isoflurane
      and 20 minutes afterwards. RESULTS: Isoflurane administration decreased coronary
      perfusion pressure, coronary vascular resistance, regional myocardial oxygen
      consumption and myocardial oxygen output. Increases in coronary oxygen saturation
      and in large coronary vein saturation were also observed. No patient experienced
      significant changes in ST segment, enzymes or decreased clearance of lactic acid.
      CONCLUSIONS: Administering 0.4% isoflurane at the end of expiration effected
      coronary vasodilation without altering oxygenation or myocardial metabolism.
      Moreover, no electrocardiographic, enzymatic or metabolic signs of myocardial
      ischemia were observed.

PMID- 9612031
TI  - [Transitory vertebrobasilar ischemic stroke during surgery to replace a hip
      prosthesis].

PMID- 9612032
TI  - [Delivery of twins with diaphragmatic hernia].

PMID- 9612034
TI  - [Regional anesthesia in present-day ophthalmology: "a well established
      technique"].

PMID- 9612033
TI  - [Laparoscopic cholecystectomy in heart transplant patients: possible
      repercussions on the graft].

PMID- 9612035
TI  - [The difficult airway].

PMID- 9612037
TI  - [A preclinical study of the effect of the animal polysaccharide chonsurid on
      reparative osteogenesis of the jaws].
AB  - Experimental studies making use of morphological and x-ray methods demonstrated
      that in comparison with control (filling of mandibular bone defects with blood
      clots) chonsuride, an animal polysaccharide, promoted earlier filling of
      postoperative bone cavities with connective tissue replacement of this tissue
      with coarse-fiber bone tissue. Secondary restructuring and mineralization of bone
      regenerate were enhanced as well.

PMID- 9612036
TI  - [A dynamic study of the intensity of mitogenesis in an osteoblast culture in the
      presence of ultrasonically dispersed hydroxyapatite].
AB  - Ceramic hydroxyapatite is frequently used in clinical practice nowadays; it is
      applied in surgical interventions on facial skull bones. This biological material
      is used as bone substitute and bone connector, but many authors claim that it is
      devoid of osteoinductor properties. Research is in progress on the effects of a
      "cold", that is, biochemically active form of ceramic hydroxyapatite on
      proliferative activity of a number of cell populations. No mitogenesis
      stimulation was observed during incubation of hydroxyapatite with osteoblast
      culture; on the contrary, a reduction of proliferative processes intensity was
      observed. Remembering that hydroxyapatite is a surfactant we repeated this
      experiment under similar conditions but used a hydroxyapatite molbfication with
      specific activity increased by two orders in comparison with its close analogs.
      Mitogenesis intensity was assessed by radiometric method from 3H-thymidine
      incorporation. The data indicated stimulation of proliferative processes in
      osteoblast culture.

PMID- 9612038
TI  - [A comparative study on a human model of the in situ absorption by enamel of
      fluorine obtained from the NaF and Na2PO3F contained in tooth pastes].
AB  - A denture model was used in situ in cross experiment to assess fluorine
      absorption by impaired enamel from toothpastes containing NaF and Na2PO3F. Six
      toothpastes were used in experiment: two contained NaF, three Na2PO3F, and one
      contained no fluorine. Twenty-five volunteers participated in experiment, who
      were fitted with dentures with sites of impaired enamel located close to each
      other. Each participant in the experiment was to accidentally clean his or her
      teeth with one of the pastes three times daily for two weeks. Then the enamel
      specimens were removed and analysed for fluorine content. The experiment lasted
      till each volunteer spent all the six pastes offered. The results indicated a
      much higher efficacy of NaF-containing pastes as regards fluorine absorption by
      impaired enamel than the ones containing Na2PO3F; the presence of decalcinated
      phosphate did not enhance the activity of Na2PO3F.

PMID- 9612039
TI  - [The use of a calcium phosphate ceramic in treating deep caries].
AB  - Clinical examinations of 36 teeth with deep caries were carried out in patients
      aged 16 to 38. Therapy with hydroxyl apatite and tricalcium phosphate was carried
      out and with calmecine for control. Additional methods for objective examination
      were assessment of pulp electric excitability and of dentin electric conduction.
      Repeated examinations of patients 1 and 6 months after treatment showed that
      hydroxyl apatite and tricalcium phosphate normalized the function of the pulp,
      caused remineralization of dentin in the bottom of carious cavity, and were
      effective in the treatment of deep caries.

PMID- 9612040
TI  - [The use of the new bacterial biopreparation Acilact in the combined treatment of
      periodontitis].
AB  - Acilact, a bacterial biopreparation representing a complex of live lyophilized
      acidophilic lactobacteria, was used in combined therapy of 45 patients with
      periodontitis of mild and medium severity. The drag was applied locally and per
      os. Clinical parameters improved after therapy; gram-positive cocci and bacilli
      predominated in local microflora; natural antibacterial resistance of the body
      improved. This method of therapy is new in principle and pathogenetically
      grounded. It results in correction of autoflora of the oral cavity and
      periodontal pouches, and, possibly, of the gastrointestinal tract. Acilact is
      well tolerated by the patients and induces no side effects, there are no
      contraindications against its administration.

PMID- 9612041
TI  - [The clinico-immunological indices of patients after the combined treatment of
      periodontitis].

PMID- 9612042
TI  - [The multivariate analysis of clinico-laboratory data in stomatology].
AB  - The authors demonstrate the potentialities of multidimensional analysis methods:
      component, cluster, and discriminant as exemplified by clinico-laboratory
      examinations of 26 patients with medium-severe periodontitis and concomitant
      diseases. A two-stage modification of multidimensional grouping of biomedical
      objects is suggested. The first stage implies detection of the principal
      components and their estimation for each examinee. The second stage consists in
      realization of multidimensional grouping method according to G. S. Kil'dishev and
      Iu. I. Abolentsev in relation to individual component values. Different
      typologically homogeneous groups of patients with a specific microbiologic and
      biochemical status evidently requiring a differentiated approach to treatment may
      be singled out within the frames of a current classification of periodontal
      diseases basing on clinical and laboratory data.

PMID- 9612043
TI  - [The diagnostic and prognostic significance of the degree of neutrophilic
      leukocyte activation in the peripheral blood of patients with odontogenic
      phlegmons].
AB  - Structural and morphologic changes in peripheral blood neutrophilic leukocytes
      were examined with the aim to diagnose and predict the clinical course of acute
      pyoinflammatory maxillofacial diseases. Classification of structural and
      morphologic signs of neutrophilic leukocyte activation levels during odontogenic
      pyoinflammatory diseases were studied using optic and electron microscopy. There
      degrees of neutrophilic leukocyte activation were distinguished: inactive,
      moderately active, and hyperactive. Inactive cells occurred in normal subjects
      and patients with mild forms of the disease, moderately active ones in patients
      with mild and medium-severe condition, hyperactive ones in those with medium
      severe and grave disease. Increased count of hyperactive neutrophilic leukocytes
      in the peripheral blood was a sign predicting a grave clinical course of the
      disease with complications.

PMID- 9612045
TI  - [The antioxidant correction of lipid peroxidation in maxillofacial phlegmons].

PMID- 9612044
TI  - [The clinical effect and dynamics of hormonal homeostasis with the inclusion of
      plasmosorption in the combined therapy of patients with maxillofacial phlegmons
      against a background of diabetes mellitus].
AB  - A positive clinical effect of plasma sorption included in multiple-modality
      treatment of patients with maxillofacial phlegmons and diabetes mellitus was
      observed. This treatment modality was conducive to normalization of hormonal
      homeostasis, it had a correcting impact on development of resistance to sugar
      reducing drugs, favorably influenced the course of pyoinflammatory process, thus
      helping cut down hospitalization period.

PMID- 9612047
TI  - [Osteo-gingivoplasty in the combined treatment of periodontitis and in the
      prevention of odontogenic maxillary sinusitis at a polyclinic].
AB  - The authors suggest a method for surgical treatment of periodontitis using
      allogenic demineralized bone tissue of adults and fetuses. This method was
      effectively used at dentistry clinics of the Samara Province starting from 1984.
      A total of 177 patients with generalized and local periodontitis of medium and
      grave severity aged 19 to 55 were operated on. The process stabilized, the teeth
      were fortified. The method is effective not only therapy of periodontitis, but
      for prevention of its complications as well, of odontogenic maxillary sinusitis
      among other conditions.

PMID- 9612048
TI  - [The role of oxygen-dependent processes in the pathogenesis of acute parotitis in
      surgical diseases of the abdominal organs].
AB  - Blood levels of lipid peroxidation products, glutathion enzymatic and
      nonenzymatic antioxidants were measured in 58 patients with parotid gland
      involvement in acute surgical diseases of the abdominal organs. The authors prove
      the predominance of free-radical processes in the mechanisms of cellular injury
      initiated by inflammation mediators and proteolytic enzymes. A conclusion is made
      on the necessity of altering the methods of prevention and therapy of acute
      postoperative parotitis.

PMID- 9612053
TI  - [The restoration of destroyed crowns of the anterior teeth with combined inlays].
AB  - An original design of a microdenture insert is suggested, as are methods of
      preparing it to restore the frontal teeth after an injury not involving the pulp.
      The insert consists of two elements permitting disposition of the parapulpar pins
      at an almost right angle, providing a reliable fixation of the insert on the
      tooth. Clinical follow-up of 25 patients with 27 inserts for up to 3 years
      demonstrated the efficacy of such treatment.

PMID- 9612054
TI  - [The use of attachments for the fixation of removable dentures].
AB  - A new design of OT-cap system attachment for removable denture fixation is
      offered improving fixation reliability, functional and esthetic characteristics
      of dentures. Establishment of attachments when the jaws are maximally tightly
      compressed helps evenly distribute the masticatory loading of the underlying
      tissues and abutment teeth individually for each patient.

PMID- 9612049
TI  - [The effect of functional tests and of a low-energy helium-neon laser on the
      local blood circulation in the area of the parotid glands].
AB  - Effects of ascorbic acid, pilocarpin, nikoshpan, and low-energy He-Ne laser on
      blood stream volumic rate were studied. Use of laser exposure as a functional
      test in examination of the salivary glands is substantiated. The studies were
      carried out in a group of 97 patients with chronic nonspecific sialadenitis.

PMID- 9612051
TI  - [An experimental and clinical study of Ossocol, a compound of hydroxylapatite and
      collagen].
AB  - Experiments on white rats revealed that introduction of Ossocol, a sponge with a
      composition of hydroxyl apatite with collagen, into a removed tooth well
      prevented mandibular atrophy and was conducive to a more smooth defect filling
      with better compact bone tissue. Ossocol use in 214 patients with bone tissue
      defects developing after tooth removal, of odontogenic cysts, sequestra, and
      after radical surgery for periodontal diseases demonstrated a positive effect of
      this agent on the course of the postoperative period: the defect was more rapidly
      replaced by bone tissue. No unfavorable local or general reactions to Ossocol
      implantation were observed.

PMID- 9612050
TI  - [The diagnosis and treatment of patients with defects and deformities of the
      inferior wall of the orbit].
AB  - The author analyzes surgical and diagnostic aspects of a new method for orbital
      bottom restoration in patients with posttraumatic deformations of the middle zone
      of the face. Diagnostic potentialities of panoramic sonography are demonstrated.
      A new method for fixation of orbital bottom fragments or osseous transplants
      replacing it with a metal implant introduced from the side of maxillary sinus is
      described in detail.

PMID- 9612052
TI  - [The reasons for complications in the use of metal-ceramic dentures].
AB  - A total of 262 patients aged 32 to 58 were examined and 246 patients aged 30 to
      60 were treated. Of the 944 cermet crowns examined complications were found in 88
      (9.34%). Ceramic fractures occurred in 20 crowns, inflammatory processes in the
      gingiva developed in 22 cases, functional overexercise of the periodontium in 21,
      failure of cement fixation in 18, apical periodontitis in 7 cases. The causes of
      these complications are analyzed and measures to prevent them worked out. If all
      preventive measures were adhered to in the treatment of 246 patients fitted with
      dentures, complications occurred three times more seldom (in only 3.14% of
      cases).

PMID- 9612055
TI  - [The experience of the joint work of the dental service and of the service for
      the formation of a healthy life style in preventing dental caries in the
      population of Luhansk Province].

PMID- 9612056
TI  - [The organization of medical care for patients with neurostomatological diseases
      in a specialized office].

PMID- 9612046
TI  - [The use of intravenous laser irradiation of the blood for the prevention and
      treatment of suppurative infectious complications in mandibular fractures].
AB  - Fifty-nine patients with mandibular fractures were treated making use of
      intravenous laser irradiation of the blood. Laser exposure had a marked
      antiinflammatory and analgesic effect, compensated for changes in disordered
      immunity status, and normalized red cell membrane structure and function as well
      as its energy supply.

PMID- 9612059
TI  - [The classification of dentomaxillary anomalies].

PMID- 9612060
TI  - [The significance of the occlusion in making dentures].

PMID- 9612062
TI  - [The surgical treatment of suppurative periradicular cysts with the preoperative
      prognosis of the size of the residual bone cavity].

PMID- 9612063
TI  - [Experience in treating fungal infection in stomatology].

PMID- 9612065
TI  - [The "examination consilium" as the form for conducting a state exam].

PMID- 9612064
TI  - [Plastic repair of the anterior wall of the maxillary sinus after sinusotomy with
      a complex autograft].
AB  - A method of repair of the maxillary sinus anterior wall after radical sinusotomy
      is presented. The defect is replaced by an osseomucosal autotransplant of an
      elongated shape cut out of the anterior sinus wall. After sinus revision the
      complex graft is placed transversely so that its edges overlap sinusal bone wound
      and fixed with sutures. Our results demonstrated the simplicity, reliability, and
      efficacy of the operation.

PMID- 9612066
TI  - [Development of HIV protease inhibitors as anti AIDS drugs: molecular design
      based on substrate transition state].

PMID- 9612061
TI  - [Reflections on the culture of scientific criticism].

PMID- 9612071
TI  - [Molecular biology of human caliciviruses, uncultivatable gastroenteritis virus].

PMID- 9612072
TI  - [Evolutionary molecular engineering moving from RNA toward protein].

PMID- 9612069
TI  - [A bracken carcinogen: chemical studies and interactions with DNA].

PMID- 9612067
TI  - [Role of virus specific protease on virion morphogenesis].

PMID- 9612068
TI  - [Clinical application of HIV protease inhibitors].

PMID- 9612070
TI  - [Molecular pathology and DNA diagnosis of phenylketonuria and
      hypermethioninemia].

PMID- 9612073
TI  - [Biotechnology policy and safety considerations].

PMID- 9612075
TI  - [On the current stage of DNA study by atomic force microscope: which stage does a
      study of DNA progress with atomic force microscope?].

PMID- 9612078
TI  - The danger of metabolic pathways with turbo design.
AB  - Many catabolic pathways begin with an ATP-requiring activation step, after which
      further metabolism yields a surplus of ATP. Such a 'turbo' principle is useful
      but also contains an inherent risk. This is illustrated by a detailed kinetic
      analysis of a paradoxical Saccharomyces cerevisiae mutant; the mutant fails to
      grow on glucose because of overactive initial enzymes of glycolysis, but is
      defective only in an enzyme (trehalose 6-phosphate synthase) that appears to have
      little relevance to glycolysis. The ubiquity of pathways that possess an initial
      activation step, suggests that there might be many more genes that, when deleted,
      cause rather paradoxical regulation phenotypes (i.e. growth defects caused by
      enhanced utilization of growth substrate).

PMID- 9612077
TI  - Conservation of baculovirus inhibitor of apoptosis repeat proteins (BIRPs) in
      viruses, nematodes, vertebrates and yeasts.

PMID- 9612074
TI  - [Review of pH measurement (4): pH meter and glass electrode Q & A].

PMID- 9612079
TI  - A ferredoxin-like domain in RNA polymerase 30/40-kDa subunits.

PMID- 9612076
TI  - The timing of cell division: Ap4A as a signal.

PMID- 9612080
TI  - Flap endonuclease homologs in archaebacteria exist as independent proteins.

PMID- 9612082
TI  - Insights into Src kinase functions: structural comparisons.
AB  - Recent structures of Src tyrosine kinases reveal complex mechanisms for
      regulation of enzymatic activity. The regulatory SH3 and SH2 domains bind to the
      back of the catalytic kinase domain via a linker region that joins the SH2 domain
      to the catalytic domain. Members of a subgroup of the Src kinase family show
      distinct features in this linker and in the loops that interact with it.
      Hydrophobicity of key residues in this region is important for intramolecular
      regulation. The kinases Abl, Btk and Csk seem to have the same molecular
      architecture as Src. Structural comparisons between serine/threonine and tyrosine
      kinases indicate a specific twisting mechanism involving the N- and C-terminal
      lobes of the catalytic domain. This motion could provide insights into the
      various mechanisms used to regulate kinase activity.

PMID- 9612083
TI  - Importins and exportins: how to get in and out of the nucleus.
AB  - Every minute, several million protein and RNA molecules must be transported
      between the cytoplasm and the nucleus of a eukaryotic cell. The characterization
      of mediators, receptors and accessory factors for different nuclear import and
      export pathways has provided a glimpse at the molecular machinery that is
      responsible for these trafficking events. It appears that both inbound and
      outbound traffic is mediated by a protein family of related transport factors
      that can be classified as importins and exportins.

PMID- 9612081
TI  - Role of the CCAAT-binding protein CBF/NF-Y in transcription.
AB  - The CCAAT motif is one of the common promoter elements present in the proximal
      promoter of numerous mammalian genes transcribed by RNA polymerase II. CBF (also
      called NF-Y and CP1) consists of three different subunits and interacts
      specifically with the CCAAT motif. In each CBF subunit, the segment needed for
      formation of the CBF-DNA complex is conserved from yeast to human and,
      interestingly, the conserved segment of two CBF subunits, CBF-A and CBF-C, are
      homologous to the histone-fold motif of eukaryotic histones and archaebacterial
      histone-like protein HMf-2. The histone fold motifs of CBF-A and CBF-C interact
      with each other to form a heterodimer that associates with CBF-B to form a
      heterotrimeric CBF molecule, which then binds to DNA.

PMID- 9612086
TI  - Presynaptic receptors: more hetero than auto.

PMID- 9612085
TI  - P/Q-type Ca2+ channel defects in migraine, ataxia and epilepsy.

PMID- 9612087
TI  - A tool coming of age: thapsigargin as an inhibitor of sarco-endoplasmic reticulum
      Ca(2+)-ATPases.
AB  - Thapsigargin is the most widely used inhibitor of the ubiquitous sarco
      endoplasmic reticulum Ca(2+)-ATPases in mammalian cells. Over the past ten years,
      this guaianolide compound of plant origin has become a popular tool in a host of
      studies directed at elucidating the mechanisms of intracellular Ca2+ signalling.
      Its remarkable potency and selectivity have been instrumental in widening our
      view of the function of intracellular Ca2+ stores to include such key aspects as
      store-operated Ca2+ entry or the involvement of the stores in protein synthesis
      or cell growth. In this article Marek Treiman, Casper Caspersen and Soren Brogger
      Christensen review the key pharmacological features of thapsigargin action; they
      also discuss some of the ways in which its unique properties have shown to be
      important for obtaining new insights into the biology of Ca2+ stores, and how
      these properties might encompass a therapeutic potential. In parallel, attention
      is drawn to some of the limitations and pitfalls encountered when working with
      thapsigargin.

PMID- 9612084
TI  - Biophysical compensation mechanisms buffering E. coli protein-nucleic acid
      interactions against changing environments.
AB  - Escherichia coli adapts to changes in growth osmolarity of at least 100-fold by
      making large changes in the amounts of intracellular water and solutes, including
      cytoplasmic K+. A wide range of in vitro salt, solute and biopolymer
      concentrations should therefore be considered 'physiological'. Paradoxically,
      these large, osmotically induced changes in cytoplasmic K+ concentration do not
      greatly affect the equilibria and kinetics of cytoplasmic protein-nucleic acid
      interactions. Biophysical effects resulting from changes in the amount of
      cytoplasmic water (such as macromolecular crowding) and in the concentrations of
      other cytoplasmic solutes appear to compensate for the effects of changes in
      cytoplasmic K+ concentration and thereby maintain protein-nucleic acid equilibria
      and kinetics in the range required for in vivo function.

PMID- 9612088
TI  - The cerebral cortex: a case for a common site of action of antipsychotics.
AB  - Recent evidence from studies of receptor occupancy and regulation in post-mortem
      brains of patients with neuropsychiatric disorders and in non-human primates is
      providing new leads in the ongoing quest to understand the pathophysiology and
      causes of schizophrenia and to develop more effective methods of treatment. These
      studies suggest that the cerebral cortex may harbour the elusive common sites of
      action of antipsychotic medications and indicate that chronic treatment with
      these drugs differentially regulates both families of dopamine receptors in this
      structure. Upregulation of the cortical dopamine D2 receptors is accompanied by a
      downregulation of the D1 sites. Balancing the opposing actions of dopamine D1 and
      D2 receptor regulation may hold the key to optimal drug therapy and to
      understanding the pathophysiology of schizophrenia. In this article, Michael
      Lidow, Graham Williams and Patricia Goldman-Rakic review the evidence supporting
      the cerebral cortex as a pivotal site for these mechanisms underlying the action
      of antipsychotics.

PMID- 9612091
TI  - Surgery for peptic ulcer in the next millennium.

PMID- 9612089
TI  - The role of IP prostanoid receptors in inflammatory pain.
AB  - Prostanoid receptor-mediated sensitization of sensory nerve fibres is a key
      contributor to the generation of hyperalgesia. It is generally thought that
      prostaglandin (PG) E2 is the principal pro-inflammatory prostanoid. Consequently,
      prostanoid EP receptors on sensory neurones have been identified as potential
      therapeutic targets. However, IP prostanoid receptors are also present on sensory
      neurones, and recent data from transgenic mice lacking the IP receptor
      demonstrate its importance in the induction of oedema and pain behaviour. PGI2,
      the primary endogenous agonist for the IP receptor, is rapidly produced following
      tissue injury or inflammation; thus, it may be of equal, or greater, importance
      than PGE2 during episodes of inflammatory pain. In this review, Keith Bley, John
      Hunter, Richard Eglen and Jacqueline Smith compare the roles of EP and IP
      receptors in nociception and suggest that the IP receptor constitutes a novel
      target for anti-nociceptive agents.

PMID- 9612090
TI  - Adenosine A2B receptors: a novel therapeutic target in asthma?
AB  - Adenosine is an endogenous nucleoside that modulates many physiological
      processes. Its actions are mediated by interaction with specific cell membrane
      receptors. Four subtypes of adenosine receptor have been cloned: A1, A2A, A2B and
      A3. Significant advancement has been made in our understanding of the molecular
      pharmacology and physiological relevance of adenosine receptors but our knowledge
      of A2B receptors lags behind that of other receptor types. Only recently have
      potentially important functions been discovered for the A2B receptors, prompting
      a renewed interest in this receptor type. A2B receptors have been implicated in
      the regulation of vascular smooth muscle tone, cell growth, intestinal function
      and neurosecretion. In this review, Igor Feoktistov, Riccardo Polosa, Stephen
      Holgate and Italo Biaggioni focus on the role of A2B receptors in mast cell
      activation and the potential relevance of this action on asthma.

PMID- 9612093
TI  - Antibiotic associated diarrhoea and enterocolitis.
AB  - C. difficile is the major aetiological agent of AAD and PMC and results from
      overgrowth of C. difficile already present endogenously or of newly acquired
      exogenous organisms after suppression of competing gut flora. C. difficile
      produces two kinds of toxins A and B. These toxins attack the colonic mucosa
      which becomes necrotic with the formation in fulminating cases of an exudative
      pseudomembrane. Toxigenic and non-toxigenic strains of C. difficile may be
      present together in an individual suffering from AAD. There is substantial
      variation among strains with respect to the quantity of lethal toxin produced.
      There are several strategies available for the investigation of C. difficile
      associated disease. Detection of toxins by neutralization with C. sordelli
      antitoxin is an easy, simple and sensitive method. Methods to deal effectively
      with silent carriers are not known because the routine administration of
      antibiotic treatment in an attempt to eradicate the carrier state would in fact
      boomerang by promoting C. difficile associated enteric disease rather than
      eliminating C. difficile.

PMID- 9612092
TI  - Adjuvant therapy in colorectal cancer.
AB  - Current evidence suggests that there is no role of adjuvant chemotherapy in stage
      I colon cancer. Patients with stage II colon cancer also do well without any
      adjuvant therapy with 5 year survivals of upto 80% with surgery alone. However,
      the role of adjuvant therapy in high risk stage II colon cancer (T4b) needs
      further evaluation. In stage III colon cancer adjuvant chemotherapy leads to
      definite survival advantage and is therefore strongly recommended. 5 FU and
      levamisole given for one year is the standard of care. 5 FU with leucovorin given
      for six months has shown good results and may become the standard of care in
      future. In rectal cancer, adjuvant treatment is not recommended for stage I
      tumours. In patients with stage II & III rectal tumours, a combination of
      chemotherapy and radiotherapy has given best results.

PMID- 9612094
TI  - An update on Clostridium difficile infection.

PMID- 9612096
TI  - Gastroduodenal mucosa in peptic ulcer: endoscopic and histological assessment.
AB  - This study aimed to assess the prevalence of endoscopic and histological
      gastroduodenitis as well as helicobacter-like organisms in patients with peptic
      ulcer. After diagnostic endoscopy, gastroduodenal biopsy specimens were taken
      from thirty patients (n = 30) with clinical and endoscopic diagnosis of peptic
      ulcer (duodenal ulcer = 25, gastric ulcer = 5). Endoscopic gastroduodenitis
      occurred in 18 patients (60%). Histological gastritis was detected in the gastric
      body or antrum in 25 (83%) and duodenitis in 17 (57%) patients. There was
      significant correlation between endoscopic and histological gastritis (p < 0.05).
      Helicobacter-like organisms occurred in 73% of the patients with peptic ulcer and
      in 88% of the antral biopsy specimens showing antral gastritis. Presence of
      helicobacter-like organisms was in particular associated with acute on chronic
      gastritis compared to chronic gastritis (p < 0.01). Moreover the patients with
      gastritis were found to belong to the older age group and 81.8% had blood group O
      +ve (p < 0.01 and p < 0.05 respectively). We conclude that presence of
      helicobacter-like organisms in patients with peptic ulcer is significantly
      associated with acute on chronic gastritis.

PMID- 9612095
TI  - Hepatocarcinogenic potential of genotype 5 of hepatitis C virus.
AB  - Evidence is emerging that hepatitis C virus genotypes have different carcinogenic
      potentials. The hepatocarcinogenicity of genotype 5, the predominant subtype in
      hepatitis C virus isolates in South Africa, is not known. We have compared the
      prevalence of genotype 5 of hepatitis C virus in 44 southern African blacks with
      hepatitis C virus-related hepatocellular carcinoma with that in a comparable
      group of patients with hepatitis C virus-induced chronic liver disease (cirrhosis
      or chronic hepatitis) in the absence of cancer. Hepatitis C virus serotypes 1 to
      6 were identified by measuring type-specific antibodies to NS4-derived peptide
      antigens. Serotype 5 was present in 48% (21/44) of the patients with
      hepatocellular carcinoma and 37% (15/41) of those with liver disease in the
      absence of hepatocellular carcinoma, an insignificant difference. Although the
      numbers of the other genotypes were small, the differences in the prevalence
      rates of these serotypes between the two groups of patients were also not
      significant. We conclude that genotype 5 of the hepatitis C virus is neither more
      nor less carcinogenic than other genotypes found in isolates in South Africa.

PMID- 9612097
TI  - Multiple large pyogenic liver abscesses of the tropics: a new entity.
AB  - BACKGROUND: Pyogenic liver abscesses most commonly occur in males in -he sixth
      decade, are usually associated with biliary tract disease, malignancy and
      immunosuppression and the mortality rate is high. We describe another form of
      pyogenic abscess occurring in females which, if treated aggressively, carries a
      much better prognosis. METHODS: Between 1986 and 1993 we treated 8 patients with
      multiple pyogenic liver abscesses. Diagnosis was established by ultrasound and CT
      scan followed by needle aspiration to confirm pus. Amoebic aetiology was excluded
      by a serology, poor response to metronidazole and biopsy of the abscess wall.
      RESULTS: The mean age of our patients was 30 +/- 7 years and there were 2 males
      and 6 females. They presented with fever and abdominal pain for more than 2
      months, tender hepatomegaly, a raised ESR and alkaline phosphatase. US and CT
      scans showed multiple large abscesses in the right lobe. Histology suggested
      chronic inflammation and with no definite organism isolated except for visceral
      larva migrans in one case. All patients underwent surgery--deroofing with
      drainage was done in four, segmental hepatic resection in three and right
      hepatectomy in one. One patient had a recurrence and underwent repeated
      resection. Only one patient died and 7 did well with no recurrence at a mean
      followup of 24 +/- 27 months. CONCLUSIONS: Large multiple cryptogenic pyogenic
      abscesses of the liver occurring mostly in young females, which respond well to
      aggressive excisional surgery may constitute a distinct clinical entity.

PMID- 9612098
TI  - Epithelial hepatoblastoma in a middle aged woman.

PMID- 9612099
TI  - Caroli's disease: a central dot means a lot.
AB  - We present here a patient of congenital non-obstructive focal dilatation of
      intrahepatic biliary radicles (Caroli's disease). The peculiar configuration of
      dilated intrahepatic biliary channels with central portal vein radicles was
      picked up sonologically as the 'central dot' sign. Awareness of this sign allows
      an accurate diagnosis without resorting to more invasive and expensive
      investigations.

PMID- 9612108
TI  - Mesenteric panniculitis.

PMID- 9612101
TI  - Pancreas divisum with chronic calcific pancreatitis: cause or coincidence.

PMID- 9612100
TI  - Percutaneous transhepatic biliary drainage in the management of obstructive
      jaundice.
AB  - BACKGROUND: Percutaneous transhepatic biliary drainage (PTBD) has been employed
      for decompression of the obstructed biliary tract to palliate jaundice and
      pruritus and for the management of cholangitis. We present our data to review the
      indications, therapeutic results and associated mortality and complications of
      this procedure. We have also studied the effect of size of drainage catheters on
      the improvement in liver functions and procedure related complications. METHODS:
      PTBD was attempted in 41 patients (18 men, age 56 +/- 12 years; 23 women, age 55
      +/- 11 years) with obstructive jaundice (37 malignant, 4 benign). RESULTS: PTBD
      was successful in 39 (95%) patients. Mean serum bilirubin and alkaline
      phosphatase concentration declined significantly (p < 0.000001 for both) after 1
      week, however thereafter decline was slow. Complete relief of pruritus and
      cholangitis was noted in most patients. Major complications such as cholangitis,
      bile leak into the peritoneum, malfunction of drainage catheter, intraperitoneal
      haemorrhage and renal failure, occurred in 11 (28%) patients, 2 (5%) of whom
      died. Large catheters (> 10 Fr) were superior to small size catheters (< 10 Fr)
      in relief of jaundice and had lower catheter related cholangitis. CONCLUSIONS: We
      conclude that PTBD is useful for palliation of malignant obstructive jaundice
      with intractable symptoms and cholangitis. Catheters larger than 10 Fr should be
      used.

PMID- 9612106
TI  - Solid and cystic tumours of pancreas.

PMID- 9612104
TI  - Omental plug closure of large duodenal defects--an experimental study.
AB  - This study was conducted to evaluate the efficacy of omental plugging in the
      management of large duodenal defects and analyse the serial histopathological
      changes occurring in the omental plug and the edges of the defect until healing
      occurred as evidenced by complete mucosal cover. The study was conducted in 12
      dogs. Through a laparotomy wound a 20 mm diameter defect was created in the first
      part of the duodenum. The abdomen was closed, leaving the defect open, for a
      period of three hours to allow peritonitis to set in. Subsequently the abdomen
      was reopened and the perforation was plugged with omentum pulled into the
      duodenal lumen and fixed to the edges. They were randomly sacrificed two at a
      time on the first week, second week, fourth week, sixth week and eight week post
      operatively. The morphology of the perforation site, adequacy of the duodenal
      lumen, and the histological picture at each stage were studied. There was no
      morbidity except in one dog which showed signs of high intestinal obstruction
      that resolved after conservative management. There was one mortality due to
      sepsis unrelated to the procedure. The omentum was firmly adherent and there was
      no evidence of leak from the site of closure. The omental plug underwent
      inflammation, necrotic changes, granulation, reduction in size and fibrosis. The
      defects decreased rapidly in size and healing was complete at eight weeks with
      the mucosa taking a normal histological appearance. None of the dogs exhibited
      luminal obstruction on autopsy. This study reaffirms the reliability of the
      omental plug in safely occluding large duodenal defects and producing healing
      through a process of inflammation, granulation, vascularisation and fibrosis
      eventually providing a normal duodenal mucosal cover to the perforation site.

PMID- 9612105
TI  - Gastrojejunocolic fistula following surgery for peptic ulcer.
AB  - This article aims to emphasize that gastrojejunocolic fistula following peptic
      ulcer surgery, though uncommon in the post vagotomy era, still continues to
      occur. We stress the changing trends in its epidemiology, aetiopathogenesis and
      treatment. The case records of 12 patients with gastrojejunocolic fistula (seen
      over a 15 year period) were reviewed. Details regarding clinical presentation,
      investigations and treatment were analyzed and the results compared with previous
      published series. All the 12 patients in this study had a short loop posterior
      retrocolic gastrojejunostomy as part of the primary peptic ulcer surgery.
      Diarrhoea and profound weight loss was present in all of them. Incompleteness of
      vagotomy was proved in all the six patients investigated for the same. The
      fistula was demonstrated in all of them on barium enema, while it was seen on
      upper GI endoscopy in 4. Eight patients were treated by a one stage resection and
      repair of fistula. A three stage procedure was performed in two.

PMID- 9612109
TI  - [Physical therapy of venous diseases].
AB  - If physical therapy like compression stockings and supervised outpatient vascular
      exercise programmes are begun early, subjective complaints can be alleviated and
      ankle flexibility and venous drainage can be improved. Incapacitating congestive
      diseases such as dermatolipofasciitis and ulcus cruris can be avoided. Once
      chronic venous congestion has led to joint capsule atrophy, stiffening of the
      ankle and muscular atrophy in the lower leg, expensive therapeutic measures
      involving professional physiotherapeutic care become unavoidable. In our own
      experience physiotherapy is most effective in combination with biomechanical
      stimulation therapy. Once the patient's equine gait has been eliminated,
      conventional walking exercise can gradually restore a physiological gait. After
      successful physiotherapy, an outpatient vascular exercise programme combined with
      optimized compression therapy contribute decisively to long-term therapeutic
      success in patients with advanced chronic venous insufficiency. Like coronary
      sports, vascular exercise programmes are covered by public health insurance.
      Along with compression therapy, they represent an efficient, cost-effective basic
      therapy for chronic venous insufficiency.

PMID- 9612110
TI  - Long-term follow-up of thromboangiitis obliterans.
AB  - BACKGROUND: To date there have been no clinical studies providing data on which
      to base a long-term medical and social prognosis of thromboangiitis obliterans
      (TAO). Against this background a retrospective investigation of the longterm
      course of patients with TAO, who attended the vascular clinic in the medical
      department of the Klinikum Westend of the Freien Universitat Berlin (Free
      University of Berlin) or the Franziskus Hospital in Berlin was carried out during
      the period between 1970 and 1990. PATIENTS AND METHODS: The 69 patients making up
      the overall group included 53 males and 16 females whose average age at the time
      of initial manifestation of TAO was 34 years. The mean interval between the
      initial manifestation of the disease and the follow up investigation was 10.7
      (range: 2-30) years. The assessment of the course over the long-term was based on
      a clinical follow-up survey or the data provided by a questionnaire. RESULTS: In
      96% of the patients symptoms began in one of the lower limbs, predominantly in
      the forefoot. During the further course of the illness, 73% of the patients
      developed symptoms in at least one other limb, either upper or lower. Since the
      initial development of symptoms, the patients had experienced an average of 5.4
      (range: 1-20) acute attacks, that is, episodes of more severe symptoms. The most
      common reason for hospitalisation was necrosis of the lower limbs, the usual site
      being the forefoot with primary involvement of the big toe in 57% of the cases.
      The mean duration of hospitalisation per hospital stay was 36.8 (range: 1-210)
      days. During the course of the disease 54 (78.2%) of the patients required an
      average of 3.7 (range: 1-17) operations, 40 (74%) undergoing one or more
      amputations. Most of the amputations were performed during the first five years
      after disease onset and the amputation rate was 26%. With the exception of a
      single lady, all the patients were smokers, and 40 (83.5%) of 48 smokers for whom
      the relevant information was available persisted with their habit after the onset
      of the disease. 8 (16.6%) of the 48 patients claimed to have stopped smoking
      during the course of their disease. Among the patients who continued to smoke,
      65% required an amputation, which was almost twice that seen in those who stopped
      smoking. In terms of number of acute attacks, surgical procedures and smoking, no
      relationship was found between early age (< 35 years) at onset and progression of
      the disease. TAO had a pronounced influence on the working life of many of the
      patients. Twelve changed their jobs because of thromboangiitis obliterans, while
      24 (34.8%) retired prematurely on a pension at the mean age of 42. CONCLUSION:
      The long-term investigation shows that TAO is associated with frequent
      hospitalisations and surgical procedures. Continued consumption of tobacco in
      particular was found to be associated with a multiplication of the amputation
      rate. An influence of patient age at disease onset on the progression of TAO was
      excluded. In 49 (71%) of the patients, the disease resulted in termination of the
      working life by either dismissal or premature retirement.

PMID- 9612103
TI  - A trial of various regimens of antibiotics in acute appendicitis.
AB  - A three year prospective randomised study was undertaken to study the efficacy of
      three regimens of antimicrobial drug combinations in reducing postoperative wound
      sepsis in acute appendicitis. Group A--Metronidazole and gentamicin; Group B-
      Metronidazole and ciprofloxacin; Group C--Metronidazole and cefotaxime.
      Randomization was done by drawing from a set of sealed envelopes. Antibiotics
      were started preoperatively once a presumptive diagnosis of appendicitis was
      made, provided there was no history of prior antibiotic usage. For simple
      appendicitis (normal or inflamed) two more doses were given postoperatively. For
      complicated appendicitis, duration of antibiotic treatment was four days
      postoperatively. All antibiotics were given intravenously to avoid variations in
      bioavailability. Wound was inspected daily till discharge and at 30 days post
      operatively or earlier if the patient had symptoms of wound infection. A total of
      128 patients completed the study. Eighty nine were simple appendicitis while the
      rest were complicated. Twenty one developed wound infection. Out of 21, 13
      occurred in group A, 5 in group B and 3 in group C. Individually, the difference
      in infection rates between group A and group C patients with simple appendicitis
      was statistically significant. Infection rates in all other groups were not
      statistically different. Cefotaxime and metronidazole combination had the lowest
      wound infection rate. Hence it is recommended for antibiotic prophylaxis.

PMID- 9612102
TI  - Clinical spectrum of chronic liver disease in north Indian children.
AB  - Recent advances in serodiagnosis of hepatotropic viruses have revolutionized the
      approach to diagnosis and understanding of chronic liver disease (CLD). There are
      few studies on CLD in children from India. The present study was planned to
      define the clinical spectrum of CLD in children, its histopathology and
      seroepidemiology. Forty children with clinical features satisfying the criteria
      for diagnosing chronic liver disease were studied. All underwent routine
      laboratory investigations, liver function tests and ultrasound scan of the
      abdomen. Liver biopsy, upper GI endoscopy and other special investigations were
      done wherever indicated. The most common presenting features were jaundice (70%),
      fever (67%), and abdominal distention (60%). On examination hepatomegaly and
      icterus (80% each) and splenomegaly (67%) were the commonest findings. Serum
      transaminases were raised in 62.5% of children while prothrombin time was
      prolonged in 75% patients. Oesophageal and/or gastric varices were seen in 13 out
      of 29 patients subjected to upper GI endoscopy. Hepatitis B surface antigen
      (HbsAg) was positive in 5 children (12.5%) while 3 (7.5%) tested positive for
      anti HCV antibody. The commonest histopathological diagnosis was infantile
      cholangiopathy (20%) followed by cryptogenic cirrhosis and idiopathic chronic
      active hepatitis (17.5% each). The study suggests that the incidence of chronic
      hepatitis B and C is rather low in childhood. However larger and longer studies
      are required to delineate the exact incidence of these conditions in childhood
      and their progression in adolescence and early adulthood.

PMID- 9612111
TI  - Is the capillary microscopic determination of the visible capillary length a
      diagnostic criterion in thromboangiitis obliterans?
AB  - BACKGROUND: The diagnosis of thromboangiitis obliterans may be difficult to
      establish in the everyday clinical setting. PATIENTS AND METHODS: In 16 patients
      with thromboangiitis obliterans vital capillary microscopy was carried out on the
      nailfold on all ten digits. The longest visible capillary length was noted. As
      controls we employed 86 healthy subjects. RESULTS: The measurement of the
      respective longest visible capillary on the nailfold revealed a visible capillary
      length of more than 0.6 mm in 38% of all patients with thromboangiitis obliterans
      (n = 16), such capillary lengths were not to be found among healthy subjects (n =
      86). CONCLUSIONS: Vital capillary microscopic determination of the visible
      capillary length is a simple-to-perform, non-invasive examination, which can help
      to establish the diagnosis.

PMID- 9612107
TI  - Multiple dermoid cysts of the omentum.

PMID- 9612112
TI  - Possible role of coagulation factor XIII in the pathogenesis of venous leg
      ulcers.
AB  - BACKGROUND: Aim of this placebo-controlled clinical study was to examine the
      expression pattern of coagulation factor XIIIa in patients with chronic venous
      leg ulcers and the impact of a 10 day topical factor XIII treatment on ulcer
      healing, leg ulcer size and radius reduction. PATIENTS AND METHODS: 24 patients
      were stratified into two groups, each consisting of 12 patients, with leg ulcers
      > 1.000 mm2, or < 1.000 mm2. Four patients of each study group were assigned to
      the control group (n = 8). All leg ulcers were treated by topical application of
      non-adhering dressings and compression therapy. Patients of the treatment group
      (n = 16) were treated by additional topical treatment off factor XIII twice daily
      for ten days. Immunohistochemical staining of leg ulcer specimens before and
      after treatment (day 10) was performed in all patients. RESULTS: The
      immunohistochemical staining of factor XIIIa in all specimens before and after
      therapy showed no significant increase in the expression of factor XIIIa.
      Comparison of the leg ulcer size, radius and daily radius reduction in the
      treatment and control group showed no significant differences in values of
      patients with leg ulcers > 1.000 mm2. However, a decreased leg ulcer size and
      radius was found in patients of the treatment group with more acute leg ulcers <
      1.000 mm2 in contrast to patients with larger leg ulcers (daily ulcer radius
      reduction from day 0-10; 0.31 mm versus 0.13 mm, p < 0.015). CONCLUSIONS: These
      results indicate that locally applied factor XIII promotes especially wound
      healing of more acute smaller venous leg ulcers. Since immunohistochemical
      staining of factor XIIIa showed no significant differences before and after
      therapy, we propose that factor XIII is inactivated rapidly after local
      application on venous leg ulcers.

PMID- 9612113
TI  - Infrared thermography in the diagnosis of Raynaud's phenomenon in vibration
      induced white finger.
AB  - BACKGROUND: Frequent use of vibrating tools over several years may lead to a
      neurovascular disturbance of finger circulation with the development of typical
      Raynaud's phenomenon, attacks being triggered by vibration and/or cold exposure.
      The condition is recognized as an occupational disease and known as vibration
      induced white finger (VWF). Aim of the present study was to evaluate the
      usefulness of infrared thermography (IRT) with a cold provocation test in the
      diagnosis of Raynaud's phenomenon in VWF. PATIENTS AND METHODS: 24 patients with
      the diagnosis of VWF, previously established by other methods, were compared with
      12 matched control subjects. We carried out IRT-measurements simultaneously on
      both hands before, directly after and 5, 10, 15, 20, and 30 mins following a 3
      min exposure of both hands to a waterbath of 12 degrees C. The results of
      temperature measurements of all fingers were analyzed and the time to complete
      rewarming of all fingers was recorded. RESULTS: The basal thermograms did not
      differ between both groups, whereas the mean finger temperatures after cold
      exposure were significantly lower in VWF-patients compared to controls, with a
      considerable individual overlap between both groups. Therefore, determination of
      absolute finger temperature reveals not to be a useful diagnostic tool in
      individual cases, but might be helpful for pharmacological studies (group
      analysis). In contrast to absolute finger temperatures, the parameter of
      rewarming time after cold exposure revealed to be diagnostic on an individual
      basis: a complete rewarming after 15 min indicates a normal vascular reactivity
      and an incomplete rewarming 30 min following the cold provocation points to an
      impaired vascular reactivity due to VWF. CONCLUSIONS: IRT revealed to be a useful
      tool in the diagnosis of Raynaud's phenomenon in VWF, and provides a sufficient
      documentation suitable for further follow-up examination.

PMID- 9612115
TI  - Demonstration of the efficacy of ginkgo biloba special extract EGb 761 on
      intermittent claudication--a placebo-controlled, double-blind multicenter trial.
AB  - BACKGROUND: A multicentric, randomized, placebo-controlled double-blind study on
      ginkgo biloba special extract EGb 761 (Tebonin forte) in patients suffering from
      peripheral occlusive arterial disease (POAD) in Fontaine stage II b was carried
      out in order to prove its clinical efficacy in this indication according to
      guidelines of European Community authorities and the German Angiological Society
      and to confirm the results of former clinical studies with EGb 761. PATIENTS AND
      METHODS: In total, 111 patients with angiographically proven POAD in Fontaine
      stage II b and intermittent claudication (pain-free walking distance < 150 m on
      the treadmill) were recruited in 5 centers and treated with either EGb 761 or
      placebo at a daily dose of 3 times 1 film-coated tablet over a duration of 24
      weeks following a 2-week placebo run-in period. The primary response variable was
      the difference of the pain-free walking distance between the start of treatment
      and after 8, 16 and 24 weeks as measured on the treadmill (walking speed 3 km/h
      and slope of 12%) under standardized conditions. RESULTS: At the start of the
      treatment period, the mean pain-free walking distances were very similar with
      108.5 m in the EGb 761 group and 105.2 m in the placebo group. At the end of the
      treatment period these values increased to 153.2 m and 126.6 m, respectively. The
      group differences were statistically significant at all three control visits with
      p = 0.017, p = 0.007, and p = 0.016. The differences for the maximum walking
      distance and the relative increases of the pain-free walking distance and the
      maximum distance were also significantly higher in the EGb 761 group with p
      values < 0.05 each. In both groups Doppler indices remained nearly unchanged
      during therapy. The subjective assessment of the patients demonstrated an
      amelioration of complaints in both groups. Tolerability was very good with no
      adverse events under EGb 761 and one case of heartburn and gastric pain in the
      placebo group. CONCLUSIONS: It can be concluded from the results of this study
      that treatment with EGb 761 in POAD patients with Fontaine stage II b is very
      safe and causes a significant and therapeutically relevant prolongation of the
      patients' walking distance.

PMID- 9612118
TI  - Ruptured cervical aneurysm of the carotid artery--case report of a rare disease.
AB  - Rupture of a cervical carotid artery aneurysm is a rare but life-threatening
      event. The diagnostic evaluation and therapeutic management of a 55-year-old
      woman with such a lesion are described. In this case, the aneurysmal rupture was
      complicated by localized Staphylococcus aureus infection confirmed by
      bacteriologic culture of excised tissue, septicemia, and prevertebral and
      intraspinal abscess. Definitive diagnosis was a ruptured mycotic aneurysm of the
      extracranial carotid artery. The origin of the infection was probably the
      patient's previously infected vascular prosthesis for hemodialysis.

PMID- 9612117
TI  - [Distal femoro-popliteal bypass using Esmarch tourniquet ischemia].
AB  - The Esmarch bandage is an effective substitute for vascular clamps in distal
      femoro-popliteal or tibial bypass surgery. Intimal trauma caused by clamping is
      avoided, vasa vasorum are preserved due to only semicircumferential dissection of
      vessels. This method is particularly suitable for heavy calcified rigid vessel
      walls. We demonstrate this technique, which was employed in 8 patients (10
      bypasses). The use of this technique requires neither a longer operation- nor
      clamping time. The postoperative course of all but one patients develops normally
      and the technique does not provoke any pathological results in the area of
      operation. Advantages of the procedure compared to conventional techniques will
      be discussed.

PMID- 9612120
TI  - Clinical predictors of cardiac complications in patients with acute ischemic
      brain disease.
AB  - Heart and brain vascular diseases present leading causes of death in civilized
      world. During development of brain ischemia cardiac complications are possible.
      The aim of this study was to determine the existence of cardiac complications'
      clinical predictors by assessing certain electrocardiographic changes in patients
      with acute ischemic brain disease (AIBD). Forty patients with AIBD, without
      previous coronary disease history were included in the study. All patients
      underwent 24 hour Holter monitoring during first 48 hours after the onset of AIBD
      which was diagnosed by computerized brain tomography. ECG-s were analyzed by
      computer and interpreted by the same cardiologist. Independent variables in
      statistical analyses were: age, AIBD, cardiological therapy atherosclerosis risk
      factors, heart disease history, degree of severity and lateralization of
      neurological incident and maximal arterial blood pressure values. Dependent
      variables were: presence/absence of ST depression and presence/absence of
      ventricular arrhythmias (VA). All parameters as well as their interreaction, were
      statistically analyzed. Results point that age and side of neurological incident
      present independent important predictive factors for appearance of ST depression,
      as well as simultaneous heart ischemia, while the same parameters have border
      value as predictive factors for VA.

PMID- 9612114
TI  - Intra-arterial and intravenous administration of prostaglandin E1 cause different
      changes to skin microcirculation in patients with peripheral arterial occlusive
      disease.
AB  - BACKGROUND: Disturbed skin microcirculation in patients with peripheral arterial
      occlusive disease (PAOD) might be affected by prostaglandin E1 (PGE1). The
      purpose of this study was to investigate local skin perfusion at the forefoot and
      toe of PAOD patients during different modes of administration of PGE1. PATIENTS
      AND METHODS: In 17 patients with severe PAOD local intradermal haemoglobin oxygen
      saturation (SHB) and dermal vascular reserve capacity, transcutaneous oxygen
      pressure (tcPO2) and laser Doppler flux (LDF) were determined during intra
      arterial (1.5 ng/kg body weight/min) and intravenous (6 ng/kg body weight/min)
      infusion of PGE1. RESULTS: SHB significantly increased at both locations during
      intravenous PGE1; intra-arterial administration significantly increased SHB in
      the skin of the forefoot only. Reserve capacity increased during intravenous
      administration and was markedly reduced during intra-arterial infusion. No
      significant changes were found regarding tcPO2 and LDF. CONCLUSIONS: These data
      suggest different therapeutic mechanisms for intra-arterial and intravenous
      administered of PGE1.

PMID- 9612119
TI  - [Johann Andreas Eisenbarth (1663-1727)--the wound physician of Oberviechtach].

PMID- 9612116
TI  - Pulsating mass after accidental artery trauma: diagnosis with duplex ultrasound
      and the role of angiography.
AB  - BACKGROUND: Pulsating mass located close to peripheral arteries is usually
      considered as a result of arterial wall injury. Clinically important is to
      distinct pseudoaneurysm from haematoma and also to evaluate proximal and distal
      arterial bed for the assessment of the injury extent. A few previous reports
      claim good results of duplex Doppler US diagnosis of iatrogenic (post
      catheterization) femoral artery injuries. This paper presents diagnostic findings
      of arterial injuries caused by accidental trauma. PATIENTS AND METHODS: A
      retrospective analysis of 49 patients with post-traumatic pulsating mass close to
      peripheral artery was performed. The diagnostic results of both sonography and
      angiography were reviewed. All the patients underwent B-mode and duplex Doppler
      US examination using PW-, color- and power Doppler imaging techniques. RESULTS:
      34 pseudoaneurysms were diagnosed correctly with typical B-mode, color/power
      Doppler images and PW-Doppler spectral waveforms. The lack of flow signal and
      distinctive B-mode images enabled proper diagnosis of 13 haematomas. In 2
      patients duplex Doppler US misdiagnosis occurred, because of secondary
      pseudoaneurysm formation, primary diagnosed as haematoma. The 47 correct US
      findings gave 96% efficacy in distinguishing pseudoaneurysm from haematoma, which
      compares well with the other studies. In 20 patients suffering from peripheral
      ischemia, US examination, in spite of proper distinction between pseudoaneurysm
      and haematoma was unable for precise estimation of proximal and distal arterial
      damage. Thus, it was successfully supported with angiography before surgical
      decision making. Angiography was also necessary in 8 patients with severe
      injuries of carotid, subclavian and palmar arch arteries, hardly accessible for
      ultrasound penetration. CONCLUSIONS: We conclude that duplex Doppler US is
      essential for noninvasive, unequivocal distinction between pseudoaneurysm and
      haematoma but it could not completely replace contrast angiography in the
      evaluation of post-traumatic pulsating mass caused by severe, extensive trauma,
      frequently complicated with peripheral ischemia or located in regions with poor
      access for ultrasound penetration.

PMID- 9612121
TI  - [Facial nerve injuries caused by firearms].
AB  - In the period from 1990 to 1994, 52 facial nerve injuries caused by fragments
      firearm projectiles were managed. Their features (localization, severity and
      extensiveness) were correlated with 37 nerve injuries in blunt head injuries with
      fracture of temporal bone. In blunt head injuries, 81.1% patients were with the
      nerve lesion in the area of geniculate ganglion (labyrinthine and tympanic
      segment). Compression of nerve with bone fragments of fallopian tube was found in
      56.8% cases, the cleft of neural sheath and intraneural hematoma were rarer,
      while the nerve tear was not found in any injured. The distal part of mastoid and
      beginning part of parotid nerve segment were injured in over 70% cases of gunshot
      injuries, and in 38.5% cases the injury was multiple. Direct suture was performed
      in 8 nerve injuries, neuroplasty in 6, and the other injuries were managed by
      skeletization of fallopian tube, nerve decompression or some other microsurgical
      procedure. Micro-surgery was performed 7-14 days after the injury.

PMID- 9612122
TI  - [Traumatic arteriovenous fistulas during a period of peace].
AB  - The aim of the study was to point out the significance of clinical vascular
      examination and angiography in diagnosis setting, with the presentation of the
      patients treated for traumatic arteriovenous (AV) fistulas, so as the
      significance of timely treatment of that specific traumatic entity. In the period
      1985-1996 11 patients with traumatic AV fistulas were treated. The most frequent
      causes of injury were bullet from firearms and blunt injury. The most frequent
      injury localization was in upper leg (4 cases). The interval from injury till
      registration and/or treatment of AV fistula was from 10 days to 33 years. Murmur
      was noticed in nine patients, thrill in eight, and weakened or absent arterial
      pulsations below the place of injury were observed in five patients. The
      diagnosis was confirmed by classic or cine-angiography. Major blood vessels were
      surgically reconstructed by various techniques, and non-major were ligated or
      percutaneous transluminal embolization was used. It was concluded that the
      noticing of murmur and thrill above the place of injury pointed out the existence
      of traumatic AV fistula, and angiography represented reliable diagnostic method
      and should be used for diagnostic, as well as therapeutic purposes. In the case
      of major blood vessel injury, surgical reconstruction is the method of choice.

PMID- 9612123
TI  - [Dermatopolymyositis and overlap syndromes].
AB  - Clinical characteristics and immunoserological features of patients with overlap
      myositis treated in Clinic for Rheumatology of Military Medical Academy in the
      period 1978-1996 are presented in the study. Retrospective and partially
      prospective study included 16 patients with the diagnosis of dermatopolymyositis
      associated with some other systemic disease of connective tissue (SDCT) in
      overlap syndrome. There were 12-females of average age 37.33 years and 4 males of
      average age 52.25 years. Complete laboratory investigation included the
      determination of muscular enzymes values. Immunoserological analyses were also
      performed (RF, Le cells, ANA, ICs, immunoglobulins, cryoglobulins and
      complement), EMNG examination of pelvis and shoulder and pH examination of skin,
      subcutaneous tissue and muscles. The combination of the diseases was found in 11
      patients, 7 were with PSS, 2 with SLE, 1 with RA and one with PAN. Three diseases
      were associated in 4 patients, SLE and RA in 2, PSS and RA in 1, thyroiditis and
      sicca complex in 1. Five-fold combination of disease was found in 1 patient. More
      frequent occurrence of fever, polyarthritis, skin manifestations, Raynoud's
      phenomenon, the involvement of serosas, lungs and heart, histological finding of
      skin and/or muscle vasculitis and larger presence of ANA, ICs,
      hypergammaglobulinemia and hypocomplementemia pointed out the dominant disorder
      of humoral immunity which was most probably connected with associated SDCT.

PMID- 9612124
TI  - [Ultrasonically-guided percutaneous needle biopsy in the diagnosis of malignant
      abdominal diseases].
AB  - In 3-year period 340 percutaneous ultrasonographically guided needle biopsies of
      abdominal organs and tissues were performed in suspected neoprocesses. Positive
      cytologic results were obtained in 77.6% and histological in 74.8% of patients.
      These results were obtained thanks to good choice of a bioptic needle and the
      technique of performing percutaneous needle biopsy under ultrasonographic control
      and sometimes in combination with radioscopy, too. Experience of both a biopsy
      performer and a cytologist or histologist with this kind of material is of great
      importance. Thanks to early histologic diagnosis, made in this way, percutaneous
      biopsy is classified as a high sensitive method and as such it forces on to be
      one of the first methods in algorithm of diagnostic procedures. Even the aim of
      this paper is to point out not only the authors ultrasonographic experience but
      also reliability, simplicity and safety of percutaneous guided needle biopsies,
      what excludes the necessity for more difficult and more expensive diagnostic
      procedures significantly reducing the examination.

PMID- 9612125
TI  - [Principles of treatment of Borrelia burgdorferi infection and Lyme borreliosis].

PMID- 9612126
TI  - [Neurologic aspects of acute intermittent porphyria].

PMID- 9612128
TI  - [Fundamentals of biologic effects of low power lasers].

PMID- 9612127
TI  - [Immunomodulating effects of allogenous blood transfusion].

PMID- 9612129
TI  - [Methods of evaluating functional values of total dental prostheses].

PMID- 9612130
TI  - [Biological effects of radiofrequency irradiation and directions of further
      research].

PMID- 9612131
TI  - [Successful treatment of people with severe body injuries caused rabid animal
      bites].
AB  - Seven patients were presented with severe injuries seeking medical help 3-10 days
      after being bitten by rabid animals. Just one of those subjects underwent timely
      and correct surgical management. Three patients were with complete, and four with
      incomplete antirabic prophylaxis. Two patients did not receive human rabies
      immunoglobulin, and another two did not receive HDC-RV vaccine. At least 3
      patients were expected to develop rabies, but it did not happen. The course of
      these cases could be explained by the existence of less pathogenic strains of
      virus in Banja Luka region.

PMID- 9612132
TI  - [Alpha coma--a prognostic sign?].
AB  - We present a patient who has developed cardiac arrest after penetrating cardiac
      wound and consequent coma, with EEG characteristics of alpha coma. At the same
      time, auditory evoked potentials-brainstem (AEPB), subcortical and cortical were
      not within physiological range. During the sixth day of coma, alfa rhythm was
      substituted with theta and delta frequency, followed by the decreased amplitude
      and prolonged latency of AEPB and complete absence of cortical and subcortical
      responses. Lethal outcome occurred in the fifth week of coma with
      neurophysiological characteristics of complete brain dysfunction. Alpha coma,
      with EEG presentation that only resemble the normal neurophysiological cortical
      activity, is rather rare neurophysiological finding present mostly in cardiac
      arrest, metabolic disturbances and intoxication. It is probably caused by
      pathological pacers of alfa rhythm, so clinical presentation of alfa coma,
      specially in a case of cardiac arrest, does not predict a favourable outcome.

PMID- 9612133
TI  - [Progressive multifocal leukoencephalopathy].
AB  - Progressive multifocal leukoencephalopathy (PML) is rare and very severe disease,
      classified into the group of subacute and viral infections of central nervous
      system (CNS), and can simulate clinical pictures of numerous degenerative
      diseases of nervous system. PML was firstly described in 1958, and pathologic
      morphologic substrate was explained in papers of Astron et al. Many years later,
      definitive diagnosis of PML was histopathologic, on the autopsy material. The
      fact that it is very rare and severe disease, very rarely diagnosed in clinical
      conditions, is the reason of our decision to present this case.

PMID- 9612134
TI  - [Effects of methylxanthine derivatives on antitumor activity and toxic side
      effect of adriamycin induced by inhibition of DNA biosynthesis].
AB  - The antitumor activity of adriamycin (ADR) was enhanced by combination with
      theobromine or pentoxifylline. Theobromine increased the concentration of ADR in
      the tumor without any effects on that in the heart and the liver. The influence
      of the combination of theobromine or pentoxifylline with ADR on the lipid
      peroxide level (indicating the ADR-induced side effect) and on DNA biosynthesis
      (indicating the side effect and antitumor activity) were examined. When ADR was
      administered into mice, the lipid peroxide level in the liver and the heart
      increased. However, the combination of theobromine or pentoxifylline did not
      enhance the ADR-induced increment of the lipid peroxide level in the liver, and
      moreover, it inhibited that in the heart. The decrease of DNA biosynthesis in the
      liver and the heart, induced by ADR, were not enhanced by combination with
      theobromine or pentoxifylline. On the other hand, the combination of theobromine
      with ADR significantly increased the inhibition of DNA biosynthesis in the tumor.
      These findings indicate that the combination of theobromine or pentoxifylline
      with ADR have no effect on the side effects of ADR in the liver and the heart,
      with the increase of antitumor activity of ADR in the tumor, and it is suggested
      that these drugs will be of value as a biochemical modulator of ADR.

PMID- 9612135
TI  - [Medicinal foodstuffs. XI. Histamine release inhibitors from wax gourd, the
      fruits of Benincasa hispida Cogn].
AB  - The methanol extract of wax gourd (Japanese name "Tougan"), the fruits of
      Benincasa hispida COGN. (Cucurbitaceae), was found to show inhibitory activity on
      the histamine release from rat exudate cells induced by antigen-antibody
      reaction. Through bioassay-guided separation, four known triterpenes and two
      known sterols were isolated as active components together with a flavonoid C
      glycoside, an acylated glucose, and a benzyl glycoside. Among the active
      triterpenes and sterols, two triterpenes, alnusenol and multiflorenol, were found
      to potently inhibit the histamine release.

PMID- 9612136
TI  - Adaptations, exaptations, and spandrels.
AB  - Adaptation and natural selection are central concepts in the emerging science of
      evolutionary psychology. Natural selection is the only known causal process
      capable of producing complex functional organic mechanisms. These adaptations,
      along with their incidental by-products and a residue of noise, comprise all
      forms of life. Recently, S. J. Gould (1991) proposed that exaptations and
      spandrels may be more important than adaptations for evolutionary psychology.
      These refer to features that did not originally arise for their current use but
      rather were co-opted for new purposes. He suggested that many important phenomena
      -such as art, language, commerce, and war--although evolutionary in origin, are
      incidental spandrels of the large human brain. The authors outline the conceptual
      and evidentiary standards that apply to adaptations, exaptations, and spandrels
      and discuss the relative utility of these concepts for psychological science.

PMID- 9612137
TI  - Liquid crystal formation in DNA fragment solutions.
AB  - The critical volume fractions pertaining to the formation of DNA liquid crystals
      were obtained from polarization microscopy, 31P-nmr, and phase separation
      experiments. The DNA length (approximately one to two times the persistence
      length 50 nm), ionic strength, and counterion variety dependencies are reported.
      The cholesteric-isotropic transition is interpreted in terms of the coexistence
      equations, which are derived from the solution free energy including
      orientational entropy and excluded volume effects. With the wormlike chain as
      reference system, the electrostatic contribution to the free energy is evaluated
      as a thermodynamic perturbation in the second virial approximation with a Debye
      Huckel potential of mean force. The hard core contribution has been evaluated
      with scaled particle theory and/or a simple generalization of the Carnahan
      Starling equation of state for hard spheres. For sufficiently high ionic
      strengths, the agreement is almost quantitative. At lower amounts of added salt
      deviations are observed, which are tentatively attributed to counterion screening
      effects. The contour length dependence agrees with a DNA persistence length 50
      nm.

PMID- 9612138
TI  - The interactions between the fluorescent dye thiazole orange and DNA.
AB  - The interaction of the fluorescent dye thiazole orange (TO) with nucleic acids is
      characterized. It is found that TO binds with highest affinity to double-stranded
      (ds) DNA [log (K) approximately 5.5 at 100 mM salt], about 5-10 times weaker to
      single-stranded polypurines, and further 10-1000 times weaker to single-stranded
      polypyrimidines. TO binds as a monomer to dsDNAs and poly(dA), both as a monomer
      and as a dimer to poly(dG) and mainly as a dimer to poly(dC) and poly(dT). The
      fluorescence quantum yield of TO free in solution is about 2 x 10(-4), and it
      increases to about 0.1 when bound to dsDNA or to poly(dA), and to about 0.4 when
      bound to poly(dG). Estimated quantum yields of TO bound to poly(dC) and poly(dT)
      are about 0.06 and 0.01, respectively. The quantum yield of bound TO depends on
      temperature and decreases about threefold between 5 and 50 degrees C.

PMID- 9612139
TI  - Short- and long-term animal studies with a plasma-sprayed calcium phosphate
      coated implant.
AB  - A commercially available hydroxyapatite (HA)-coating was investigated in a 4- and
      24-week animal study. HA-coated and uncoated commercially pure (c.p.) titanium
      threaded implants were inserted in rabbit tibia and femur. Qualitative histology
      showed giant cells and macrophages around both types of implants.
      Histomorphometry demonstrated significantly more bone in contact to the HA-coated
      specimens at both follow-up periods. In contrast, bone area measurements (the
      amount of bone inside and/or outside the threads) revealed significantly higher
      percentages of bone around the uncoated c.p. titanium controls after 6 months of
      follow-up. The inferior amount of bone around the HA-coated implants in the
      longer-term perspective may relate to macrophage-induced resorption.

PMID- 9612140
TI  - Immunohistochemistry of soft tissues surrounding late failures of Branemark
      implants.
AB  - The objective of the present investigation was to characterize the cellular
      composition of the soft tissues surrounding consecutively retrieved late failures
      of Branemark implants. Criteria for implant failure were signs of loss of
      osseointegration (radiographic peri-fixtural radiolucency and mobility). The
      clinical history of the implants did not include adverse symptoms. At the time of
      retrieval, percussion-induced pain was experienced at 4/8 implants, but no
      macroscopical signs of inflammation or infection or infection was observed.
      Immunohistochemistry was applied on 6 marginal peri-implant specimens and on
      specimens of deeper tissues associated with the previously load-bearing implant
      surface from 8 failed implants, whereas 6 clinically healthy mucosal specimens
      and 4 hyperplastic biopsies from stable implants served as controls. The
      immunohistochemical evaluation showed that the soft tissues surrounding failed
      implants contained a large number of macrophages (CD68), HLA-DR positive cells,
      lymphocytes and plasma cells preferentially accumulated towards the removed
      implant surface. PMNs were a rare finding. Downgrowth of epithelium, in some
      cases encapsulating the whole fixture, was observed in sections where an intact
      implant/soft tissue interface was preserved. Healthy control mucosal specimens
      always contained labelled cells, albeit in a low amount, whereas hyperplastic
      control samples displayed an intense inflammatory and immunological response with
      numerous positive cells and PMNs scattered throughout the biopsy. In conclusion,
      failed implants were characterized by a chronic inflammatory response of the
      surrounding tissues with macrophages as the predominant labelled cell type, while
      hyperplastic tissues around stable implants were distinguished by an acute
      inflammatory process. These findings suggest that an on-going infection is
      unlikely to be the etiological factor for the late failures of dental implants
      examined in this study.

PMID- 9612141
TI  - Bone morphogenetic protein-2 for peri-implant bone regeneration and
      osseointegration.
AB  - Recombinant human bone morphogenetic protein-2 (rhBMP-2) induced bone
      regeneration and osseointegration was evaluated in supraalveolar peri-implant
      defects in 5 beagle dogs. Alveolar bone was reduced 5 mm in height in mandibular
      premolar areas and the premolars were extracted. Three 10 mm titanium fixtures
      were placed 5 mm into each reduced alveolar crest, leaving 5 mm in a
      supraalveolar position. Alternate quadrants in consecutive animals received a
      surgical implant consisting of 2 ml rhBMP-2 (0.43 mg/ml) in a type I bovine
      collagen carrier, or the carrier alone (control). Fixtures and surgical implants
      were submerged under the gingival flaps. The healing interval was 16 weeks.
      Histometric and radiographic evaluations were made. Defect height averaged (+/-
      SD) 5.3 +/- 0.2 and 5.1 +/- 0.2 mm for rhBMP-2 and control defects, respectively
      (P > 0.05, n = 5, paired, t-test) Bone regeneration (height) averaged 4.2 +/- 1.0
      and 0.5 +/- 0.3 mm for rhBMP-2 and control defects, respectively (P < 0.05). Bone
      regeneration (area) averaged 6.1 +/- 6.3 and 0.2 +/- 0.2 mm2 for rhBMP-2 and
      control defects, respectively (P > 0.05). Osseointegration within the confines of
      the defect averaged 19.1 +/- 10.1% and 8.2 +/- 4.6% for rhBMP-2 and control
      defects, respectively (P > 0.05). Osseointegration within regenerated bone
      averaged 29.1 +/- 9.8% and 65.3 +/- 15.3% for rhBMP-2 and control defects,
      respectively (P < 0.05). Osseointegration within the retained alveolar bone
      averaged 67.1 +/- 4.6% and 68.1 +/- 3.6% for rhBMP-2 and control defects,
      respectively (P > 0.05). The results suggest that there is a potential for rhBMP
      2 induced bone regeneration and osseointegration in surgical peri-implant
      defects.

PMID- 9612142
TI  - The effect of a calcium hydroxide paste on wound healing and osseointegration of
      dental implants. A pilot study in beagle dogs.
AB  - The aim of this investigation was to evaluate the effect of a new calcium
      hydroxide suspension (Osteoinductal) on the healing process of endosseous dental
      implants after placement. The material, composed of 25% calcium hydroxide, 25%
      Oleum pedum tauri and 50% vaselinum album, was developed with the intention to
      accelerate and to increase the mineralized bone to implant contact during the
      healing phase. Eight adult beagle dogs were used in this study. Prior to the
      beginning of the study the dogs had all mandibular premolars extracted. After the
      extraction sites had healed for 3 months, implant osteotomies were performed. On
      one side of the mandibular premolars extracted. After the extraction sites had
      healed for 3 months, implant osteotomies were performed. On one side of the
      mandible Osteoinductal was applied into the osteotomies before placement of the
      implants, whereas the other side did not receive Osteoinductal. A total of 48
      implants were placed with two losses during the entire study period. Two dogs
      were sacrificed 1 week, 2 weeks, 4 weeks and 3 months after implant placement.
      The specimens were evaluated histologically and histomorphometrically. In the
      histological evaluation an intense inflammatory reaction towards the calcium
      hydroxide suspension was found leading to a destruction of the bone surrounding
      the implants after 1 and 2 weeks. A giant cell reaction against the test material
      was visible at 4 weeks. At 3 months no inflammatory and no giant cell reaction
      could be depicted in the test group. The mean direct bone to implant contact or
      inflammatory tissue to implant contact showed no differences between test and
      control group for 1 and 2 weeks. Although statistically not significant, there
      was a clinical significant difference in the mineralized bone to implant contact
      between test and control group for the last two timepoints (i.e. 4-week
      specimens: test group 2.3 +/- 0.9%, control group 26.8 +/- 11.1%; 3-month
      specimens: test group 10.5 +/- 12.7%, control group 60.7 +/- 13.7%). This study
      indicates that the use of the calcium hydroxide suspension Osteoinductal has a
      detrimental effect on wound healing and osseointegration of dental implants and
      cannot be recommended for use with dental implants.

PMID- 9612143
TI  - Custom-made root analogue titanium implants placed into extraction sockets. An
      experimental study in monkeys.
AB  - The aim of this investigation was to evaluate clinically and histologically a new
      custom-made, root analogue titanium implant placed into extraction sockets in
      monkeys (Macaca fascicularis). Three adult monkeys were used in this
      investigation. After raising full thickness flaps on the buccal and lingual side,
      the upper central and lateral incisors were extracted. Each tooth root was
      machine copied to 1 titanium analogue using a new CAD/CAM-system. The implants
      were installed in the respective extraction sockets and the flaps sutured back.
      After 6 months of healing biopsies were taken and processed according to the
      cutting-grinding technique. The percentage of mineralized bone-to-implant contact
      was measured as a fraction of the rough implant surface using computer-assisted
      analysis. The main clinical problem that occurred during implant placement was
      the fracture of the buccal alveolar wall. The histometric evaluation showed a
      mean mineralized bone-to-implant contact of 41.2 +/- 20.6%. In this investigation
      it could be shown that implants fabricated by laser copying will osseointegrate.
      The presented data encourage the performance of clinical and experimental trials
      evaluating the new system utilizing improved second generation CAD/CAM equipment.
      Such studies are currently underway.

PMID- 9612144
TI  - Initial interfacial healing events around calcium phosphate (Ca-P) coated oral
      implants.
AB  - The bone response to different calcium phosphate (Ca-P) coated and non-coated
      titanium implants was evaluated in a goat animal model. Two types of Ca-P
      coatings have been investigated: an experimental plasma-spray bilayered Ca-P
      coating (FA-HA) and an amorphous RF magnetron sputter coating (Ca-P-a). Fifty
      four conical screw shaped implants were inserted in the lateral and medial
      femoral condyles of 18 Saanen goats. After implantation periods of 3, 12 and 24
      days, the bone-implant interface was evaluated histologically and
      histomorphometrically. Light microscopical evaluation revealed that bone
      formation on the Ca-P coated implants proceeded faster. At 24 days higher
      percentages of bone contact were measured for both Ca-P coated implants than for
      non-coated implants. However, this difference was only significant for the FA-HA
      coated implants. On basis of these findings, we concluded that Ca-P coatings show
      improved bone response due to an initial difference in bone cell response.

PMID- 9612145
TI  - Maxillary sinus augmentation using different grafting materials and dental
      implants in monkeys. Part III. Evaluation of autogenous bone combined with porous
      hydroxyapatite.
AB  - The aim of this study was to evaluate clinically, histologically, and
      histometrically the use of autogenous bone combined with porous hydroxyapatite
      (Interpore 200) as a grafting material for maxillary sinus augmentation
      procedures. In 4 adult male rhesus monkeys (Macaca mulatta) the 1st, 2nd and 3rd
      maxillary molars on one side of the jaws were extracted. After a healing period
      of 3 months, maxillary sinus augmentation procedures were performed in each
      monkey, and the sinuses were grafted with autogenous bone from the monkeys' tibia
      mixed in a 3:1 ratio with porous hydroxyapatite. At the same time, 2 pure
      titanium plasma-sprayed IMZ cylinder implants were immediately placed into the
      augmented sinuses (i.e. simultaneous implants-loaded group). After 4 months, 2
      additional similar implants were placed into the previously augmented sinuses
      (i.e. delayed implants-loaded group). Four months later, the abutment connection
      was performed and all 4 implants were loaded with a gold-alloy bridge for 6
      months (i.e. until sacrifice of the animals). The contralateral side of each
      monkey received similar treatment with the exception that the extractions were
      performed 7 months after those in the opposite side and that the implants were
      not loaded. Thus, 2 additional study groups (i.e. simultaneous implants unloaded
      group and delayed implants unloaded group) were obtained. Clinically, all loaded
      implants were stable at the day of sacrifice. Histologically, the grafted sinuses
      exhibited a significant amount of new bone formation. The porous hydroxyapatite
      granules appeared integrated with the newly formed bone. Histometric analyses
      revealed that delayed implant placement resulted in a greater amount of direct
      mineralized bone-to-implant contact in the augmented area than the simultaneous
      implant placement. Furthermore, the percentage of direct mineralized bone-to
      implant contact was far more significant in the residual bone than in the
      augmented area. It was concluded that the autogenous bone/porous hydroxyapatite
      graft combination enhanced bone formation and mineralized bone-to-implant contact
      in the augmented sinuses and that the delayed implant placement may be favorable
      for sinus augmentation procedures.

PMID- 9612146
TI  - Associations between clinical parameters assessed around implants and teeth.
AB  - The aim of the present study was to clinically assess the peri-implant and
      periodontal conditions 1 year after placement of oral implants (ITI Dental
      Implant System) in partially edentulous patients. In all, 127 patients (median
      age 50 years, range 17 to 79) were examined. They were all treated according to a
      concept of comprehensive dental care and had received fixed partial dentures
      (FPD). Significant differences were observed between implants and contralateral
      control teeth with respect to mean pocket probing depth (PPD) (2.55 mm at
      implants/2.02 mm at teeth), mean probing attachment level (PAL) (2.97 mm/2.53 mm)
      and bleeding on probing (BOP) (24%/12%) (Wilcoxon matched pairs sign rank test, P
      < or = 0.01), whereas mean modified plaque index (0.22/0.30), mean modified
      bleeding index (0.35/0.44) and mean recession (-0.42 mm/-0.51 mm) did not
      significantly differ between implants and teeth. Compared to control teeth, the
      width of keratinized mucosa at implants was significantly smaller at lingual, but
      not at buccal aspects. Regression analyses showed no significant association
      between the amount of keratinized mucosa and degree of inflammation. Recession,
      PPD and PAL were slightly influenced by the amount of keratinized mucosa
      indicating greater resistance to probing. Grouping the implants according to
      various lengths, type of fixation of the FPD or combination with natural teeth
      did not result in statistically significant different clinical parameters,
      whereas grouping according to different localization within the oral cavity did.
      For example, the mean PAL in 83 anterior implants was 2.52 mm, whereas 175
      posterior implants had a mean PAL of 3.18 mm (Mann-Whitney U-test, P < or =
      0.01). Regression analyses between the mean PAL for all implants in each patient
      and the mean PAL of the corresponding dentition revealed an r2 of 0.23 (P < or =
      0.01). Using multiple regression analysis, the mean PAL of the implants showed to
      be significantly influenced by the combined factors "fullmouth" PII, "fullmouth"
      BOP and mean PAL of all teeth. The results of this study suggest that in
      partially edentulous patients the overall periodontal condition may influence the
      clinical condition around implants and thus reinforces the importance of
      periodontal treatment prior to and supportive periodontal therapy after the
      incorporation of osseointegrated oral implants.

PMID- 9612147
TI  - Some clinical and radiographical features of submerged and non-submerged titanium
      implants. A 5-year follow-up study.
AB  - The present study reports on the results of a follow-up examination of patient
      material, 5 years after the installation of the fixed supraconstruction. The
      patient group comprised 11 individuals. Briefly, a split-mouth technique of
      treatment was used. In the right side of the mandible the traditional 2-step
      surgical approach for implant installation was used. In the left jaw quadrant a 1
      step surgical procedure was used. A clinical and radiographical examination was
      performed 5 years after the initial connection of the supraconstruction to the
      implants. At the 5-year follow-up examination all 61 implants examined at the 18
      month follow-up were still in service and found to be clinically stable
      irrespective of the surgical procedure used. Furthermore, the results of the
      present clinical and radiographical follow-up study demonstrate that the marginal
      bone level at implants placed anteriorly in the edentulous mandible and
      supporting fixed supraconstructions is stable between 18 and 60 months
      irrespective of whether placed according to a 1-step or 2-step surgical
      procedure.

PMID- 9612148
TI  - Controlled local delivery of tetracycline HCl in the treatment of periimplant
      mucosal hyperplasia and mucositis. A controlled case series.
AB  - The purpose of this controlled case series was to assess the adjunctive efficacy
      of controlled topical tetracycline HCl application in the treatment of infection
      associated periimplant mucositis or mucosal hyperplasia. Eight patients with at
      least 2 endosseous implants showing clinical signs of periimplant mucosal
      hyperplasia or mucositis were enrolled. All implants received supra- and
      subgingival scaling, with half of the implants receiving adjunctive controlled
      local delivery of tetracycline HCl (test). Control implants did not receive any
      other therapy aside from scaling. Clinical parameters were assessed at baseline,
      4, and 12 weeks. Scaling plus controlled local delivery of tetracycline HCl
      markedly reduced periimplant mucosal hyperplasia in 4 of 5 test implants and
      demonstrated a trend towards a reduction of bleeding on probing scores. Scaling
      alone had no effect on mucosal hyperplasia in the 2 control implants presenting
      with this condition nor bleeding on probing scores. In both groups, plaque index
      scores were slightly reduced at 4 weeks but returned to baseline values at 12
      weeks, whereas pocket probing depths, clinical attachment levels, and probing
      bone levels remained unchanged during the course of the trial. The observed
      trends suggest that scaling plus controlled local delivery of tetracycline HCl
      may have beneficial effects. Randomized controlled trials employing a sample size
      high enough to reach sufficient statistical power are needed to definitively
      assess the efficacy of controlled local tetracycline HCl delivery on periimplant
      diseases.

PMID- 9612149
TI  - The rehabilitation of the severely resorbed maxilla by simultaneous placement of
      autogenous bone grafts and implants: a 10-year evaluation.
AB  - The long-term success of Branemark implants has been previously reported. The
      success rate of the same implants, when associated with autologous grafts, seemed
      much less predictable. In the present study it is demonstrated that when these
      implants are installed in conjunction with an autologous corticocancellous hip
      graft, either onlay or inlay, the cumulative success rate remains at 95% for
      individual implants in non-smokers. The short extracorporal time might be an
      explanation. On the other hand, the same approach in patients with congenital
      defects or who underwent radiotherapy is deceptive. The use of hyperbaric oxygen
      may dramatically improve these results.

PMID- 9612150
TI  - Postoperative exposure of bioresorbable GTR membranes: effect on healing results.
AB  - The goal of this investigation was to evaluate the effect of postoperative
      exposure of two different bioresorbable membranes on the guided tissue
      regeneration (GTR) healing results compared to nonexposed sites. In each of 25
      patients one pair of contralateral intrabony lesions was treated either with
      polylactic acid (PLA) or polyglactin 910 (PG-910) membranes. Postoperative
      exposure occurred in 9 PLA and 13 PG-910 sites. Standardized clinical [papillary
      bleeding index (PBI), gingival recession (REC), probing pocket depth (PPD),
      probing attachment level (PAL)] and radiographic examinations (digital
      subtraction radiography) were performed immediately before (baseline) and 6 and
      12 months postoperatively (p.o.). Subgingival bacterial samples from surgical
      sites were evaluated by culture at baseline, 6 weeks, and 6 and 12 months p.o.
      Six months after surgery the changes (delta) of REC were significantly (P < or =
      0.05) greater in exposed than in nonexposed sites, independently of the membrane
      material (median): exposed sites, delta REC = -1 mm; nonexposed sites, delta REC
      = 0.0 mm. However, 12 months p.o. no significant differences were found due to a
      decrease in the initial recessions in exposed sites. Although a higher percentage
      of exposed than nonexposed sites harbored periodontal pathogens 6 weeks p.o. at
      the gingiva-faced membrane surface, membrane exposure did not have a significant
      negative effect on delta PPD, delta PAL, or radiographic bone density changes 6
      and 12 months p.o. Both membranes showed significant gains in PAL and bone
      density in both exposed and nonexposed sites. In conclusion, this study
      demonstrates that with consistent infection control the postoperative exposure of
      PLA and PG-910 membranes has no significant negative effect on the regeneration
      outcome, although higher initial gingival recessions must be expected than in the
      nonexposed sites. However, in exposed sites plaque and infection control were
      clearly impeded by the rough, exposed membrane surfaces and by the initially
      negative gingival morphology.

PMID- 9612151
TI  - The reliability of implant-retained hinging overdentures for the fully edentulous
      mandible. An up to 9-year longitudinal study.
AB  - The treatment of fully edentulous mandibles by means of implant-supported hinging
      overdentures has become a routine therapy, although long-term data on the success
      rate of implants and prostheses are lacking. This longitudinal study examined 207
      consecutively treated patients who received, during the past 10 years, 449
      Branemark implants to retain a mandibular hinging overdenture, mainly on a Dolder
      bar. Clinical parameters and standardized radiographs taken at every recall visit
      with an interval of 6-12 months were used to judge the implant rigidity in the
      jawbone, the marginal bone level, and attachment level changes. The cumulative
      implant failure rate at 9 years was 3%. After loading, implant loss was
      concentrated during the first 12 months, with only one failure observed at 22
      months. A radiographically determined bone loss of 0.7 mm was observed during the
      first year. From the second year, a mean annual bone loss of 0.05 mm occurred.
      The attachment loss, calculated as the sum of probing pocket depth plus the
      recession, was 0.07 mm/year and paralleled the changes in marginal bone level
      over time. The rigidity of the implant-bone interface revealed an increase over
      time, as shown by a decrease in Periotest values. The bar-overdenture
      complications were related to relining (23%), untightening of the retention clip
      (10%), and renewal of the prosthesis (7%). When magnets or ball attachments were
      used, more aftercare was needed. Fracture of the antagonistic full denture
      occurred in 7% of patients. The present data indicate that the mandibular
      overdenture therapy on two (Branemark) implants is a very reliable and cost
      effective treatment, even in a long-term perspective for the fixed full
      mandibular prosthesis and especially in elderly patients.

PMID- 9612152
TI  - Fluoride uptake in dentin with and without simulating dentinal fluid flow.
AB  - The aim of the present study was to compare fluoride uptake of dentin with and
      without simulating dentinal fluid flow. Eighty-five dentinal discs were prepared
      from retained human molars. Seventeen discs were used to assess baseline fluoride
      content (controls). Sixty-eight discs were evenly distributed among two
      experimental groups and were fixed for 24 h in a two-chamber device allowing for
      simulating dentinal fluid flow. Thirty-four samples were treated with dentifrice
      slurry containing a low fluoride concentration (Elmex, dilution 1:5); the
      remaining discs were treated with a solution of a high fluoride concentration
      (Elmex Fluid). For the perfused group, each of the 17 discs of the high and low
      concentration fluoride groups were constantly perfused during the experiment. The
      remaining fluoridated specimens were not perfused. All specimens were assayed for
      KOH-soluble fluoride and structurally bound fluoride. Structurally bound fluoride
      was determined in three successive layers of 20 microns each. Uptake of KOH
      soluble fluoride was significantly higher in the specimens fluoridated with Elmex
      Fluid compared to the samples treated with the dentifrice slurry. The uptake of
      KOH-soluble fluoride was not influenced by perfusion of the dentinal discs.
      However, perfusion resulted in lower acquisition of structurally bound fluoride
      in the samples treated with the dentifrice slurry. After application of Elmex
      Fluid, no significant difference was found in the amount of structurally bound
      fluoride between the perfused specimens and non-perfused samples. It is suggested
      that further studies on fluoride uptake in dentin should use a model simulating
      outward dentinal fluid flow.

PMID- 9612153
TI  - In vitro culture of human dental pulp cells: some aspects of cells emerging early
      from the explant.
AB  - Cells emerging from a dental pulp explant were studied in order to elucidate the
      origin of precursor cells implicated in the formation of reparative dentin in
      vivo. Such cells observed at the very early stage of culture (days 5-10) were
      different from fibroblast-like cells obtained after one subculture. These early
      cells were round or elongated, with thin spinous processes, highly mobile, and
      contained numerous lipid vesicles. Incorporation of 1-[14C]palmitic acid did not
      show an increased incorporation of radiolabeled total lipids or triglycerides
      into these early cells compared to cells after four subcultures or control skin
      fibroblasts, suggesting that the lipids in vesicles were not synthesized by the
      cells. Since these cells also show a high level of fluid phase uptake via
      macropinocytosis, it is suggested that these lipids originate from
      macropinocytosis. Between days 10 and 20, these cells spontaneously start
      conversion into cells that have a fibroblast-like morphology, are less mobile,
      and lack lipid vesicles. Their morphology, movement, and macropinocytosis suggest
      that these cells, which migrate from the pulp explants, are mesenchymal cells
      related to mononuclear phagocytes/histiocytes.

PMID- 9612154
TI  - Three-dimensional finite element analysis of the retention of fixed partial
      dentures.
AB  - Four three-dimensional mathematical models were generated, each representing a
      three-unit fixed partial denture. The second premolar and second molar were used
      as abutments. Different associations of dental support preparation were tested. A
      500-N axial load was applied to the pontic. Strains were analysed for each dental
      support by means of a three-dimensional finite element analysis technique. The
      results showed that the greatest strains were observed on the weaker abutment,
      the premolar. The cervical margin facing the edentulous area is affected most,
      regardless of the model or the dental support. The greater the dento-prosthetic
      differential surface between the two dental supports (thus the greater the
      retention differential) the higher the risk of unsealing.

PMID- 9612155
TI  - Morphometric analysis of collagen and elastic fibers in normal skin and gingiva
      in relation to age.
AB  - The morphometric parameters of the human gingival elastic fiber network were
      determined by image analysis and compared with human skin elastic fibers in
      relation to age. Similarly, collagen fibers were also investigated in both
      tissues. In this study, 47 healthy patients, 10-75 years old were studied for
      gingiva and another 50 patients in the same age range were included for skin
      biopsies. Three groups were compared: group 1 from the age of 10-24 years, group
      2 from 25 to 49 years, and group 3 from 50 to 75 years. The diameters of the
      oxytalan fibers were invariable in both tissues, whatever the age considered. On
      the other hand, the diameters of elastic fibers increased regularly with age in
      the gingiva (P < 0.01) and in the skin (P < 0.01) between each age group. The
      area fraction occupied by the oxytalan fibers decreased significantly in both
      tissues (P < 0.01) for the skin and (P < 0.001) for the gingiva. The area
      fraction occupied by the gingival elastic fibers remained constant with age while
      the skin elastic fibers increased significantly with age between groups 2 and 1
      (P < 0.01) and between groups 3 and 2 (P < 0.001). In the mid-dermis and in the
      mid-gingiva, the diameters of the collagen fibers increased strongly with age,
      between groups 2 and 1 (P < 0.01) and between groups 3 and 2 (P < 0.001). The
      area fraction occupied by the collagen bundles increased regularly with age in
      the mid-gingival (P < 0.05 between each age group), while a significant decrease
      was observed in the mid-dermis from the age of 50-75 years (P < 0.05). The
      results obtained contribute to a better understanding of some modifications which
      dermis and gingiva undergo with aging and provide data to perfect diagnosis and
      therapy in odontology and dermatology.

PMID- 9612156
TI  - Comparison of Ho:YAG versus Nd:YAG thoracoscopic laser treatment of pulmonary
      bullae in a rabbit model.
AB  - OBJECTIVE: To determine the relative efficacy and morbidity of Ho:YAG versus
      Nd:YAG laser treatment of bullous lung disease in an animal model. SUMMARY
      BACKGROUND DATA: Laser coagulation procedures for treatment of emphysematous
      pulmonary bullae and heterogeneous emphysema continue to evolve. The role of
      lasers in lung volume reduction surgery remains controversial due to issues of
      relative efficacy and morbidity. The Nd:YAG laser is most commonly used for these
      procedures. We hypothesized that the shallower penetration of the Ho:YAG laser
      may be better suited for laser bullae coagulation and emphysema lung volume
      reduction with increased efficacy and reduced lung injury. METHODS: Thirty New
      Zealand White rabbits (15 normal rabbits; 15 with bullous lung disease) were
      evaluated with Ho:YAG compared to Nd:YAG laser exposures. Bullae were coagulated
      by either Ho:YAG or Nd:YAG treatment. In all animals (bullous-induced and
      normals), unaffected lung tissue in the upper lobes and contralateral lungs were
      treated with 5 spot exposures of Nd:YAG and Ho:YAG, each to assess depth of lung
      injury. Animals were sacrificed at Days 0, 7, and 21 and their lungs were
      examined histologically. RESULTS: Ho:YAG and Nd:YAG exposures caused equivalent
      lung injury to normal lung tissue. In the acute phase, parenchymal necrosis depth
      was similar for both Ho:YAG and Nd:YAG (850 +/- 273 microns vs. 900 +/- 270
      microns respectively, p = 0.7). By Day 7, lung necrosis depth was 925 +/- 133
      microns Ho:YAG vs. 1225 +/- 235 microns Nd:YAG (p = 0.33), and lung fibrosis
      depth was 300 +/- 134 microns Ho:YAG vs. 558 +/- 127 microns Nd:YAG (p = 0.11).
      By Day 21, pulmonary parenchymal necrosis was not seen. Pleural fibrosis depth
      was maximal at Day 21, reaching 250 +/- 102 microns for Ho:YAG vs. 300 +/- 156
      microns Nd:YAG (P = 0.88). Pleural necrosis depth was 67 +/- 42 microns Ho:YAG vs
      48 +/- 34 microns Nd:YAG (p = 0.42) on Day 7 and resolved by Day 21. During
      surgical coagulation procedures, the Ho:YAG laser was dramatically more efficient
      in coagulating bullae. The Ho:YAG laser required less exposure at equivalent
      power and resulted in immediate desiccation of bullae, in sharp contrast to the
      Nd:YAG laser. CONCLUSIONS: Because the Ho:YAG was more effective and did not
      result in more acute lung injury than the standard Nd:YAG laser in this study,
      Ho:YAG lasers may have improved potential for laser treatment of bullae or lung
      volume reduction surgery (LVRS) compared to Nd:YAG lasers.

PMID- 9612157
TI  - Investigational study of the use of Er:YAG laser versus dental drill for caries
      removal and cavity preparation--phase I.
AB  - OBJECTIVE: We determined that the Er:YAG pulsed 2.94 micron radiation was
      successful in the removal of caries, cavity preparation, and etching prior to
      acid etching. SUMMARY BACKGROUND DATA: The laser group was compared to a control
      group in which the high-speed drill was employed. Parameters measured included
      histological evaluation of the pulp, scanning electron microscopy of the surface
      morphology of the tooth, dye penetration studies, bond strength measurements, and
      rating of the laser's ability to remove caries and form the preparation. METHODS:
      We collectively evaluated 60 patients with 106 teeth in both the laser and
      control groups over a 1-year period. Teeth were treated in vivo and then
      extracted immediately, at 2 days, 1 month, and up to 1-year to assess pulpal
      healing, surface morphology, and the quality of the preparation, restoration, and
      pain. RESULTS: The dental laser was shown to be equal or better than the drill in
      the tested procedures of caries removal, cavity preparation, and etching prior to
      acid etching. The scanning electron microscopy revealed no microfracturing, open
      dentinal tubules, and effective etching with the laser having a mean of 2.7 with
      an optimum rating of 3. The histological testing confirmed that the pulp was not
      compromised using the laser with scores of theta for hemorrhage, 0.47 for
      hyperemia, and 0.12 for inflammation on a scale of 0 to 3 where 0 is no effect.
      CONCLUSIONS: The FDA has recently cleared the Er:YAG to remove all classes of
      caries, form the cavity preparation, and modify the enamel and dentin prior to
      acid etching. In this Phase I study conducted as part of the clinical trials,
      there were no complications and no tooth was compromised. Patients were
      consistently treated without anesthesia with the same or better results than the
      drill as confirmed by scanning electron microscopy and histological studies.

PMID- 9612158
TI  - Dentin and pulp response to Erbium:YAG laser ablation: a preliminary evaluation
      of human teeth.
AB  - OBJECTIVE: We determined the real effect of Erbium:YAG laser ablation on human
      teeth in vivo. SUMMARY BACKGROUND DATA: We advocated the idea that overheating of
      teeth, specially pulp damage can be avoided if correct laser parameters are used.
      METHODS: We evaluated human premolars scheduled for extraction during orthodontic
      treatment. Before tooth extraction, an oval cavity preparation was made with a
      pulsed Er:YAG laser. After extraction, the teeth were decalcified for 6 weeks.
      Routine staining with haematoxylin and eosin was performed on longitudinal
      section. One hundred seventy-two sections were prepared and examined in a light
      microscope. RESULTS: Under Er:YAG laser application, reduction of the dentin
      layer was observed. Dentinal tubules had a radial course up to the surface. No
      cracks or structural injury were observed. Inflammatory reaction in the pulp was
      not found. The vascularity of the pulp was normal. The odontoblasts were of the
      usual spindle-like or star-like cell shape. The cementum and epithelial
      attachment were healthy. No changes of structure or indications of inflammation
      were observed. CONCLUSIONS: The results of this in vivo experiment on human teeth
      confirm safety of Er:YAG laser ablation of enamel and dentin under the conditions
      described.

PMID- 9612159
TI  - Laser-assisted outpatient septoplasty results on 120 patients.
AB  - OBJECTIVE: I describe a new outpatient technique of septoplasty, advocated to
      minimize and simplify surgery under local anesthesia with new laser instruments
      especially designed. SUMMARY BACKGROUND DATA: This quick technique takes 5
      minutes and has a specific clinical application in chronic nasal obstruction due
      to moderate anterior septal deviation in adults. It is less invasive that
      traditional septoplasty and potentially more advantageous in terms of decreased
      patient recovery time, less morbidity, lower medical costs, and faster return to
      full activity. METHODS: I retrospectively review my experience with 120 patients,
      from August 1995 to November 1996, with a patient evaluation pre- and
      postoperatively, at first by a direct interview with clinical examination and
      acoustic rhinometry, then by a telephone interview with strictly standardized
      questioning. RESULTS: Of the 120 patients, a surgical success rate of 96% on the
      nasal obstruction was achieved. Many patients experienced improvement on other
      symptoms like nasal discharge, frequent sneezing, frequent headaches, recurrent
      rhinosinusitis, and sense of smell and sleep troubles. Observations comparing pre
      and post-operative rhinometries revealed a significant increase of the size of
      the mean minimal cross-sectional areas (MCA) of the narrow side, at the anterior
      part of the nose, an increase of the mean nasal cavity volume (NCV), and a
      decrease of mean nasal airway resistance (NAR). CONCLUSIONS: This new technique
      appears to be a safe, quick, simple, predictable, bloodless, and virtually
      painless in-office procedure without side effects. These encouraging good
      preliminary results must be confirmed by further study and long-term follow-up.

PMID- 9612160
TI  - Effect of Nd:YAG laser irradiation for removal of intracanal debris and smear
      layer in extracted human teeth.
AB  - OBJECTIVE: The objective of this study was to evaluate the efficacy of Nd:YAG
      laser to remove debris and smear layer on the instrumented root canal walls in
      vitro. SUMMARY BACKGROUND DATA: There have been some contradictory reports about
      the efficacy of Nd:YAG laser to remove debris and smear layer. MATERIALS AND
      METHODS: Thirty-six extracted single mandibular incisor human teeth were used in
      this study. The teeth were sectioned at an enamel-cementum junction and the roots
      were instrumented up to # 50-K files size, then divided into three groups of 12
      teeth. The first group (Group 1) was unlased as a control, and in the other two
      groups, root canals were irradiated by Nd:YAG laser at two different parameters;
      1 W, 20 pps (Group 2) and 2 W, 20 pps (Group 3). After laser irradiation, the
      roots were bisected longitudinally, observed by scanning electron microscopy, and
      evaluated the condition of cleanliness on the root canal walls according to our
      criteria. RESULTS: In most of the specimens in Groups 1 and 2, debris and smear
      layer remained on the root canal wall surfaces covering the orifices of dentinal
      tubules. However, specimen in Group 3 showed very clean root canal walls with
      debris and smear layer evaporated, melted, fused, and recrystallized in most
      cases. Statistical analysis demonstrated a significant difference between Groups
      1 and 3. CONCLUSIONS: These results suggest that Nd:YAG laser is useful to remove
      debris and smear layer and causes melting of internal structures on the
      instrumented root canal walls at the parameters of 2 W and 20 pps.

PMID- 9612161
TI  - Polymerization shrinkage of restorative resins using laser and visible light
      curing.
AB  - OBJECTIVE: This in vitro investigation compared the amount of linear shrinkage
      that occurs when a light-cured composite resin is cured with a visible light
      source, and also with an argon laser. SUMMARY BACKGROUND DATA: When composite
      resins are light-cured, they undergo a certain degree of polymerization
      shrinkage, which can be clinically significant and affect the efficacy of the
      restoration. A new protocol utilizes laser curing instead of conventional visible
      light. METHODS: Two hybrid composite resins were used, Z100 and TPH-Spectrum.
      Dimensional change was measured in a linear direction, using a calibrated light
      microscope. A total of 40 samples of composite resin was tested using two curing
      lights, and two hybrid composite resins, resulting in four groups of 10 samples
      (n = 10) each. According to manufacturer instructions, curing time for the laser
      was 10 sec, and for visible light was 40 sec. RESULTS: With TPH-Spectrum, the
      mean shrinkage with visible light was 0.583% compared to that with laser light
      which was 0.591%. With Z100, the mean shrinkage with visible light was 0.565%,
      compared to that with laser light which was 0.551%. CONCLUSIONS: There was no
      significant difference in amount of shrinkage of hybrid composite resins between
      using visible light or laser light. There was also no significant difference in
      shrinkage between the two hybrid composites for either light source.

PMID- 9612162
TI  - Laser literature watch.

PMID- 9612164
TI  - Carbon dioxide laser tissue welding: an alternative technique for tubal
      anastomosis?
AB  - Microsurgical tubal anastomosis is the gold standard for treatment of tubal
      occlusion. The present study was performed to establish the feasibility of tubal
      anastomosis by welding tissue with a defocused CO2-laser beam during laparotomy
      and with an endoscope. In an animal experiment, 70 white New Zealand rabbits were
      randomized in 2 study groups (E1, E2) and 3 control groups (C1, C2, C3) as
      follows: C1, 10 animals, no operation, as controls for the efficiency of the
      insemination technique; C2, 5 animals, spontaneous healing after tubal segment
      resection, to quantify spontaneous recanalization of the tube; C3, 15 animals,
      microsurgical end-to-end adaption after tubal segment resection; E1, 20 animals,
      laser welded anastomosis after segment resection via laparotomy; E2, 20 animals,
      laparoscopic laser welded anastomosis after segment resection. The pregnancy rate
      in C1 was 80%. None of the animals in C2 but 60% of the rabbits in C3 conceived.
      After sutureless anastomosis by laser welding 50% of the laparotomized, and 40%
      of the laparoscopically operated group became pregnant. Morphological examination
      of the oviducts after relaparotomy showed comparable patency rates of 70% in C3,
      70% in E1, and 65% in E2. Whereas no dehiscence of anastomoses was observed in
      C3, 20% of the welded tubes in E1 and 22.5% in E2 were dehiscent. Tubal
      anastomosis took approximately three times as long laparoscopically as during
      laparotomy. Thus, laser welding as a sutureless alternative technique of tubal
      anastomosis should be viewed critically. A reduction of sutures through laser
      assisted anastomosis might, however, be considered.

PMID- 9612163
TI  - Pharmacokinetic analysis of octa-alpha-butyloxy-zinc phthalocyanine in mice
      bearing Lewis lung carcinoma.
AB  - OBJECTIVE: In this study, the pharmacokinetics of octa-alpha-butyloxy-zinc
      phthalocyanine (8-alpha-bo-ZnPc) was studied with regard to Lewis lung carcinoma
      in mice after intravenous administration of 7.8 mumole/kg body weight at
      different incubation intervals. SUMMARY BACKGROUND DATA: The newly synthesized
      potential photosensitizer 8-alpha-bo-ZnPc is characterized by a high absorption
      coefficient at the far red wavelength (735 nm) with a good singlet oxygen quantum
      yield. METHODS: After intravenous administration of 7.8 mumole/kg body weight in
      mice bearing Lewis lung carcinoma, the accumulated photosensitizer was chemically
      extracted (at incubation intervals of 2, 6, 12, 24, 48, and 168 hours) from
      selected tissues, and the concentrations were measured by absorption
      spectroscopy. RESULTS: The parenchymatous organs, liver, and spleen showed
      maximum 8-alpha-bo-ZnPc concentrations after 6 hours of incubation. An extensive
      uptake was detected in lung extracts taken at 6, 12, 24, and 48 hours. The
      malignant tissue did not accumulate high 8-alpha-bo-ZnPc during the entire
      investigation period. The photosensitizer extracted from muscle, representing
      normal tumor-surrounding tissue and skin, was even lower. CONCLUSIONS: Because of
      the extremely low accumulation rate of the tumor, 8-alpha-bo-ZnPc is suggested to
      be administered topically or in combination with a suitable carrier system in
      order to increase the photosensitizer concentration in the target tissue, as well
      as to decrease the loss of dye to other tissues.

PMID- 9612165
TI  - Treatment of hypersensitive teeth using neodymium:yttrium-aluminum-garnet lasers:
      a comparison of the use of various settings in an in vivo study.
AB  - The spectrum of the methods available to treat hypersensitive teeth is very
      great. The chances for success in the use of these different therapies are
      equally variable. Faced with the already successful effort of the Nd:YAG laser in
      the treatment of exposed tooth necks, the effectiveness of the use of different
      settings of the Nd:YAG laser on exposed dentine was examined in this clinical
      study. In the case of comparison of the therapy success of the laser settings
      amongst one another, no significant difference could be found. This leads us to a
      conclusion, that laser irradiation is therapeutically effective at very low
      settings.

PMID- 9612166
TI  - Mechanism of aneurysm formation after 830-nm diode-laser-assisted microarterial
      anastomosis.
AB  - OBJECTIVE: The process of aneurysm formation after laser welding is described.
      SUMMARY BACKGROUND DATA: The mechanism of aneurysm formation after laser-assisted
      microarterial anastomosis is presently unclear. METHODS: A series of 830-nm diode
      laser-assisted longitudinal aortorrhophy with a condition of 400 to 500 J/mm2 for
      1 cm length of anastomosis versus conventional manual anastomoses were performed
      in 90 Wistar rats. To compare this technique with normal media process, a
      histologic examination of aneurysm formation was conducted. RESULTS AND
      CONCLUSIONS: The results show that there are two important factors that cause
      aneurysm formation after laser-assisted anastomosis: 1) the vessel wall is
      damaged by laser heating; 2) proliferation of collagen fiber at the adventitia is
      absent during media reconstruction.

PMID- 9612167
TI  - Low-level laser therapy in the management of disorders of the maxillofacial
      region.
AB  - OBJECTIVE: The authors analysed the effects of low-level laser therapy (LLLT) on
      the treatment of maxillofacial disorders. SUMMARY BACKGROUND DATA: Pioneer work
      published by Mester et al. opened a new frontier in the clinical treatment of
      many disorders with the use of LLLT. Although LLLT is not well accepted in many
      places, its use is growing steadily in others, including Europe and more recently
      in Brazil. METHODS: One hundred forty-one female and 24 male patients, between 7
      and 81 years of age (average = 39.2 years old), suffering from disorders of the
      maxillofacial region were treated with 632.8-nm, 670-nm, and 830-nm diode lasers
      at the Laser Center of the Universidade Federal de Pernambuco. The disorders
      included temperomandibular joint pain, trigeminal neuralgia, muscular pain,
      aphatae, inflammation, and tooth hypersensitivity both postoperatively and in
      small hemangiomas. Most treatment consisted of a series of 12 applications (twice
      a week), and in eight cases a second series was applied. Patients were treated
      with an average dose of 2.5 J/cm2. RESULTS: One hundred twenty out of 165
      patients were asymptomatic at the end of the treatment, 25 improved considerably,
      and 20 were symptomatic. CONCLUSIONS: These preliminary results indicate that
      LLLT is an important tool and brings many benefits for the treatment of many
      disorders of the maxillofacial region.

PMID- 9612169
TI  - Laser literature watch.

PMID- 9612168
TI  - The carbon dioxide laser as an aid in apicoectomy: an in vitro study.
AB  - OBJECTIVE: To achieve the required goal of optimally sealing the apical section
      and the root-canal when performing an apicoectomy, the authors decided to use the
      CO2 laser as an additional aid. SUMMARY BACKGROUND DATA: The CO2 laser has
      previously shown to have an excellent sealing effect on dentin surfaces. METHODS:
      In this in vitro study, the authors examined the effects of CO2 laser application
      in apicoectomies with the help of color penetration tests and scanning electron
      microscopic (SEM) examinations. Sections and root canals were irradiated with low
      power (0.5 W) in continuous wave mode for totally 20 sec. The thermal stress for
      the adjacent tissues attaching thereto is moderate as shown by infrared
      spectroscopy. RESULTS: A comparison with nonirradiated samples revealed that CO2
      laser irradiation reduced color penetration at the section to a minimum. Also,
      irradiation of the root-canal wall resulted in satisfactory sealing of the
      surface. These findings were supported by the results of the SEM examinations.
      CONCLUSIONS: CO2 laser treatment optimally prepares the tooth for final
      intraoperative filling because of sealing of the dentinal tubules, the resultant
      elimination of niches for bacteria and the sterilizing effect of the laser.

PMID- 9612170
TI  - Two-photon photodynamic therapy.
AB  - OBJECTIVE: We demonstrate the use of infrared excitation in conjunction with an
      efficient two-photon absorbing dye and a photosensitizer in photodynamic therapy.
      SUMMARY BACKGROUND DATA: An efficient two-photon absorbing dye is excited by
      short infrared (800 nm) laser pulses, which transfer its energy to the
      photosensitizer and the photosensitizer, in turn, generates the singlet oxygen.
      METHODS: A new approach to photodynamic cancer therapy based on the strong two
      photon absorption of certain newly developed organic molecules. Near infrared
      pulsed laser light efficiently excites these molecules which, in turn, transfer
      the energy to the photosensitizer used in photodynamic therapy. RESULTS: A newly
      synthesized two-photon absorbing dye 4-[N-(2-hydroxyethyl)-N-(methyl) amino
      phenyl]-4'-(6-hydroxyhexyl sulfonyl)stilbene (APSS), which exhibits a strong two
      photon absorption at 800 nm, and upconverted fluorescence at 520 nm, in solution
      in the presence of a photosensitizer was found to generate singlet oxygen under
      infrared excitation (800 nm). The generation of singlet oxygen in a reaction
      system containing two-photon absorbing dye and photosensitizer under infrared
      excitation has been chemically detected by using ADPA (9,10-anthracenedipropionic
      acid) as singlet oxygen detector. CONCLUSIONS: The efficient two-photon
      absorption of certain chromophores can be used to extend photodynamic therapy to
      the near infrared spectral region. Whereas the photosensitizer itself may not
      exhibit two-photon absorption, it could be used in conjunction with one of these
      new chromophores. The chromophores can act as "photon harvesters" whereby they
      absorb two photons of near infrared light and transfer the energy to the
      photosensitizer, which can generate singlet oxygen in the presence of atmospheric
      oxygen.

PMID- 9612171
TI  - Dye-enhanced protein solders and patches in laser-assisted tissue welding.
AB  - OBJECTIVE: This study examines the use of dye-enhanced protein bonding agents in
      805 nm diode laser-assisted tissue welding. A comparison of an albumin liquid
      solder and collagen solid-matrix patches used to repair arteriotomies in an in
      vitro porcine model is presented. SUMMARY BACKGROUND DATA: Extrinsic bonding
      media in the form of solders and patches have been used to enhance the practice
      of laser tissue welding. Preferential absorption of the laser wavelength has been
      achieved by the incorporation of chromophores. METHODS: Both the solder and the
      patch included indocyanine green dye (ICG) to absorb the 805 nm continuous-wave
      diode laser light used to perform the welds. Solder-mediated welds were divided
      into two groups (high power/short exposure and low power/long exposure), and the
      patches were divided into three thickness groups ranging from 0.1 to 1.3 mm. The
      power used to activate the patches was constant, but the exposure time was
      increased with patch thickness. RESULTS: Burst pressure results indicated that
      solder-mediated and patched welds yielded similar average burst strengths in most
      cases, but the patches provided a higher success rate (i.e., more often exceeded
      150 mmHg) and were more consistent (i.e., smaller standard deviation) than the
      solder. The strongest welds were obtained using 1.0-1.3 mm thick patches, while
      the high power/short exposure solder group was the weakest. CONCLUSIONS: Though
      the solder and patches yielded similar acute weld strengths, the solid-matrix
      patches facilitated the welding process and provided consistently strong welds.
      The material properties of the extrinsic agents influenced their performance.

PMID- 9612172
TI  - Comparison of wound healing process using Argon and Krypton lasers.
AB  - OBJECTIVE: We compared the wound healing process on Sprague-Dawley rats between
      Argon Laser and Krypton Laser, and calculated the laser actual doses after
      correction on wound healing on rats and estimated the clinical doses on wound
      healing for human skin. SUMMARY BACKGROUND DATA: Laboratory work provided some
      support for the use of low-intensity laser radiation in wound healing. Some
      studies found that laser irradiation may either enhance, inhibit, or has no
      effect on the function of a variety of microorganisms and cells. Animal studies
      also offered some basis for treatment. Improvements, particularly in the earliest
      phases of wound healing, have been reported following laser irradiation. METHODS:
      We used Argon Laser (488-514 nm) and Krypton Laser (670 nm) in the study. The
      laser beam was delivered through a system of fiber optic in Argon Laser and
      reflector in Krypton Laser. The rats treated were restrained in a Plexiglas cage
      without anesthesia during the laser irradiation period. The percentage of the
      wound healing acceleration in days and size, actual doses, and estimated clinical
      doses were calculated as follows: AccD = (1-TD/CD) x 100%, AccS = (1-TA/CA) x
      100%, AD = D(in) - D(gl) - D(SR) and ECD = AD = D(sr), respectively. RESULTS: The
      acceleration effects of wound healing in days (AccD) were 22.93% and 14.54%, size
      reductions (AccS) were 41.93% and 30.41% at the optimal stimulative incident dose
      of 20 J/cm2. Zero bioactivation shown at the incident doses of 80 J/cm2 and 100
      J/cm2. The inhibitory effects of wound healing in days were -7.72% and -3.37%, in
      size reduction were -13.35% and -12.88% at the maximal inhibitory incident dose
      of 140 J/cm2 for Argon and Krypton Lasers, respectively. The actual doses were
      5.21 J/cm2 and 4.03 J/cm2, the estimated clinical doses were 5.50 J/cm2 and 4.25
      J/cm2 at optimal stimulative incident dose 20 J/cm2 for Argon and Krypton Lasers,
      respectively. CONCLUSIONS: Low power laser therapy at the appropriate dosimetric
      parameters can provide the acceleration effects of wound healing on rats. The
      effects were dependent with the doses and laser wavelengths used. In this
      experiment, the optimum stimulative dose was 20 J/cm2 and the Argon Laser with
      488 nm was more effective than the Krypton Laser with 670 nm. The zero
      bioactivation and inhibition effect of wound healing on rats occurred in Argon
      Laser and Krypton Laser.

PMID- 9612173
TI  - Laser therapy for fibromyositic rheumatisms.
AB  - BACKGROUND AND OBJECTIVES: The objectives of this study is to treat the cases of
      fibromyositic rheumatisms untreatable with other therapies. The authors chose
      defocalized laser beams because some experimental studies had showed their
      analgesic and anti-phlogistic effects on experimental phlogosis. Since 1980 non
      surgical laser effects were often noncomparable because of the lack of common
      treatment protocols. This summarizes fifteen years of clinical observations as to
      the purpose of identifying some indications on laser treatment of defined
      pathologies included in fibromyositic rheumatism. STUDY DESIGN/MATERIALS AND
      METHODS: 846 patients with different types of fibromyositic rheumatisms were
      submitted to defocalized laser therapy from 1980 to 1995. Criteria for selection
      included age, sex, and pathological pictures. Control groups were used to compare
      results with those of traditional methods. Diodes and CO2 lasers were employed,
      to exploit the photothermic and photochemical effects of the laser radiations to
      the fullest extent. RESULTS: On the whole, results were positive in comparison
      with other methods both as regards recovery time and persistence of results.
      Results were evaluated on the basis of subjective (such as local pain) and
      objective (hypomotility, phlogosis) criteria. CONCLUSIONS: Results obtained
      (approximately 2/3 of the patients benefited from the treatment) indicate that
      there are greater advantages in use of laser over other presently available
      methods. Standardalization of treatment protocols deserves further studies.

PMID- 9612174
TI  - CO2 laser surgery in osteomyelitis.
AB  - OBJECTIVE: To prove that the thermal energy of CO2 lasers, when applied on the
      fistula, pyogenic sac, and septic bone in cases of osteomyelitis, creates an
      aseptic area, diminishes relapses, and promotes healing in those patients
      treated. SUMMARY BACKGROUND DATA: CO2 laser surgery, whether used in a focused or
      unfocused manner, has been incorporated into surgical procedures because of its
      incisive, coagulating, and antiseptic properties. These forms and characteristics
      are especially useful in the treatment of chronic osteomyelitis. METHODS: The
      authors recorded their experiences with 80 patients (10-75 years) with different
      types of chronic osteomyelitis. Classical surgical procedures were performed
      incorporating the CO2 laser beam. RESULTS: Of the 80 patients, 45 healed with a
      single application combined with sequestrectomy implant removal, etc. Twenty-two
      patients needed up to three sessions to heal. Twelve patients did not heal, 1
      asked for an amputation, and 3 were unavailable for follow-up procedures. We did
      not evaluate antibiotics prescribed, or cultures taken, due to the multiplicity
      of drugs used by chronic osteomyelitis patients with disease progression, and the
      various permutations and combinations of germs involved. CONCLUSIONS: Although
      CO2 laser beam surgery cannot replace classic surgical procedures in
      osteomyelitis, it is an important adjunctive tool that helps enhance surgical
      effects and assists in the healing process.

PMID- 9612175
TI  - Pulsed alexandrite laser technology for noninvasive hair removal.
AB  - OBJECTIVE: Determination of the efficacy of pulsed Alexandrite Laser technology
      for rapid noninvasive hair removal. SUMMARY BACKGROUND DATA: Although previous
      studies have already shown that Ruby lasers are capable of noninvasive hair
      removal, a technology for the substantial increase of treatment speed is of great
      interest. METHODS: We have used a 2 msec free running pulsed Alexandrite (lambda
      = 755 nm) laser operated at a repetition rate of up to 5 pps at energy fluences
      of 25-40 J/cm2 to treat a wide range of body sites on 126 patients in conjunction
      with a fiber delivery system and a transparent target ruler. A transparent gel
      was used as epidermal heat sink. The study lasted 15 months. Pretreatment as well
      as follow-up hair count per cm2 was performed to determine the level of success.
      Treatments were repeated when 1-2 mm growth was observed. RESULTS: The average
      hair count before the second treatment was found to be close to 65% of the
      pretreatment count. The average hair count 3 months after the last treatment, was
      found to be lower than 12%. The interval between treatments ranged from 4 weeks
      to 3 1/2 months. CONCLUSIONS: The 2 msec pulsed Alexandrite laser technology is
      effective for the removal of unwanted hairs, ranging from fair to dark, except
      when hairs are absent in the shaft depending on the stage of their growth cycle.
      This results in the necessity of a few treatments or touchups. Adverse effects
      are minimal and transient.

PMID- 9612176
TI  - Laser literature watch.

PMID- 9612177
TI  - Of frogs, princes, and realities.

PMID- 9612178
TI  - A review of the literature: transmyocardial laser revascularization.
AB  - BACKGROUND AND OBJECTIVE: Transmyocardial laser revascularization is an
      investigational procedure that improves chronic angina that is not amenable to
      other forms of therapy. The theorized mechanism is an increased supply of
      oxygenated blood to the myocardium via the creation of left ventricular
      transmural channels. The objective of this review is to facilitate an
      understanding of the current work published in the literature on the subject of
      transmyocardial laser revascularization. METHODS: Using Melvyl Medline, all
      pertinent literature associated with transmyocardial laser revascularization was
      sought and reviewed. CONCLUSION: The research in transmyocardial laser
      revascularization is growing. The results of the current work in animals is
      conflicting with some showing a benefit from this procedure and others that
      refute its effectiveness. This may be the outcome of differing methodology, which
      has yet to be evaluated. Although the results of human trials are positive, the
      overall effectiveness in comparison with the conventional forms of therapy has
      not been addressed. It is, therefore, a procedure worthy of continued study.

PMID- 9612179
TI  - Laser intraductal photocoagulation of bilateral parotid ducts for reducing
      drooling of cerebral palsied children: a preliminary report.
AB  - Previous reports suggested that surgical treatment was effective to reduce
      abnormal, profuse drooling in children with low cognitive function, but with risk
      of complications. Laser photocoagulation might be an option to simplify the
      procedure and decrease complications. Our study considered whether laser
      photocoagulation could improve drooling in children with cerebral palsy (CP). CP
      children with drooling were recruited from the pediatric rehabilitation clinic,
      all of whom had persistent profuse drooling after 6 months of conservative
      treatment. They received neodymium:yttrium aluminum garnet (Nd:YAG) laser for
      intraductal photocoagulation to bilateral parotid ducts, and were followed up for
      2 to 3 months. Each patient was assessed before and after the procedure by: 1)
      questionnaire-based semiquantitative assessment of drooling severity and
      frequency (Thomas-Stonell and Greensberg 1988); 2) quantitative assessment of
      saliva amount by collection of stimulated saliva for 2 minutes in cooperative
      children. Six CP children with severe drooling received laser photocoagulation,
      five of them had remarkable decrease of drooling 1 month later. Patients had cool
      liquid intake soon after the procedure, and were discharged on the second day
      after treatment. A period of transient face swelling ranged from 6 to 37 days. No
      antibiotic treatment was indicated nor were any complications noted after the
      procedure. As a result of these studies, it is suggested that laser intraductal
      photocoagulation of bilateral parotid duct could be used as a simple and
      effective procedure for reducing drooling in CP children, and would avoid
      complications from conventional surgery.

PMID- 9612180
TI  - Magnetic resonance imaging of the lumbosacral spine under compression.
AB  - OBJECT: This study was undertaken to duplicate the more physiological imaging of
      lumbar disk herniation possible with the "sitting magnetic resonance imaging
      (MRI)" that exists at Harvard and Zurich. METHOD: A compression frame was
      constructed of plywood that would fit into a standard MRI machine. A patient
      lying in the frame, on extending the bent knees, would experience a compressive
      force on his lumbar and thoracic spine, thus duplicating the higher intradiscal
      pressures found in the sitting position. RESULTS: It was found that in 50% of
      patients so studied there was reproduction of their pain syndromes as well as
      augmentation of disk herniation by MRI. CONCLUSION: The compression frame used
      during MRI of the spine results in a more physiological representation of
      herniated disks seen in the erect position.

PMID- 9612181
TI  - The efficiency of root canal disinfection using a holmium:yttrium-aluminum-garnet
      laser in vitro.
AB  - The aim of the present study was to determine the bactericidal effect of a
      holmium:yttrium-aluminum-garnet (Ho:YAG) laser on root canals in vitro. The
      efficiency of different laser settings was compared. The in vitro examinations
      revealed extensive bacterial reduction in extracted, endodontically prepared
      teeth that had been incubated with Streptococcus faecalis with the most favorable
      results at a setting of 5 Hz and 2 W. In average, 99.98% of the bacteria injected
      in the root canal could be eliminated. Considering this bactericidal effect, the
      application of the Ho:YAG laser in root canal treatment appears to be very
      efficient.

PMID- 9612182
TI  - The use of carbon dioxide laser in pit and fissure caries prevention: clinical
      evaluation.
AB  - In this 4-year follow-up in vivo controlled study, 112 human permanent first
      molars from children between 6 and 11 years old were used to investigate the
      viability of the carbon dioxide (CO2) laser in promoting caries-free occlusal
      surfaces in permanent molars as an isolated form of treatment or associated with
      conventional fissure sealants. The findings suggest that occlusal caries
      prevention only by means of CO2 laser irradiation is not effective; that the
      utilization of photoactivated sealants, as well as its association with CO2
      laser, applied over the occlusal fissures, are effective means of preventing
      occlusal caries, and that the application of CO2 laser over occlusal fissures
      prior to the application of a photoactivated fissure sealant improves the
      retention of the sealant.

PMID- 9612183
TI  - Pilot in vitro toxicity study of 5-ALA and Photofrin in microvascular endothelial
      cell cultures.
AB  - Complicated hemangiomas are unique problems in which intervention with the proper
      laser can be an ideal solution. In this study we evaluated the toxicity of 5
      Aminolevulinic acid (5-ALA) and Photofrin using in vitro models. The in vitro
      toxicity of 5-ALA and Photofrin was examined in a microvascular endothelial cell
      (MEC) culture system. The measurement of the percentage of MEC killed by various
      drug concentration using fluorescence viability assay. MEC incubated with 5-ALA
      at various concentrations for evaluation of dark toxicity showed less than a 50%
      cell kill. A comparison of different intervals of subcultured MEC showed that the
      early subculture (3 days after primary culture) is more vulnerable than later
      subculture (7 days after). Cells treated with Photofrin at various concentrations
      exhibited less than 50% cell kill (dark toxicity). The comparison of different
      intervals of subculture (3 days and 7 days after primary culture) showed a result
      similar to that of 5-ALA. All controls showed 0% cell kill. In conclusion, both 5
      ALA and Photofrin are capable of destroying human microvascular endothelial cells
      in vitro. Drug concentrations and the power density for photodynamic therapy
      should be considered and will be included in our subsequent studies.

PMID- 9612184
TI  - ISMISS Meeting, Zurich, January 1997. 15th course for percutaneous endoscopic
      spinal surgery and complimentary techniques.

PMID- 9612185
TI  - Laser literature watch.

PMID- 9612186
TI  - A brief history of clinical photodynamic therapy development at Roswell Park
      Cancer Institute.

PMID- 9612187
TI  - Photodynamic therapy of endobronchial and esophageal tumors: an overview.
AB  - From 1982 to March 1996 we treated 211 patients with endobronchial tumors and 106
      patients with esophageal tumors using photodynamic therapy (PDT) in an ongoing
      study of the efficacy of PDT. This paper is an overview of our results and the
      evolvement of our current techniques for using PDT.

PMID- 9612188
TI  - Photodynamic therapy for early stage bronchogenic carcinoma.
AB  - Photodynamic therapy utilizing Photofrin has proved to be an effective modality
      that can be used in the treatment of a wide variety of solid tumors and luminal
      cancers. The effectiveness of photodynamic therapy (PDT) was demonstrated in our
      institution in 1980 for the treatment of lung cancers, and increasing attention
      has been focused on this new treatment technique. Over the past decade, 240
      patients (283 lesions) with central type lung cancers have been treated in our
      hospital. Overall complete remission was obtained in 39.6% of the 112 lesions,
      partial remission in 59.4%, and no remission was obtained in 1.0%. However, among
      95 early stage lesions, CR was obtained in 79 (83.2%) and 71 cases were disease
      free at 3 to 176 months. We conclude that PDT is efficacious in the treatment of
      superficial lung cancer where complete remission may be achieved.

PMID- 9612190
TI  - Photodynamic therapy in Barrett's esophagus.
AB  - OBJECTIVES: This report presents clinical results using photodynamic therapy for
      dysplasia and superficial esophageal cancer in Barrett's esophagus. METHODS:
      Forty-five (45) patients with Barrett's esophagus and dysplasia were treated with
      photodynamic therapy using sodium porfimer 2.0 mg/kg as the photosensitizing
      drug. Fifteen patients also had 16 superficial esophageal cancers (0-1.5 cm; Tis
      T2, N-0, M-0). Red light (630 nm) was delivered to the esophageal mucosa by a
      diffuser inserted through the endoscope or via a windowed esophageal centering
      balloon designed to improve targeted delivery of light during photodynamic
      therapy. Patients were maintained on omeprazole and were followed for 6-62 months
      following photodynamic therapy. RESULTS: Photodynamic therapy produced mucosal
      damage in treated areas. Ablation of dysplastic or malignant mucosa was followed
      by healing and conversion of approximately 75-80% of treated Barrett's mucosa to
      normal squamous epithelium in all patients. Complete elimination of Barrett's
      epithelium was found in 16 patients. Areas of dysplasia were eliminated in 35 of
      the 45 patients. All 16 malignancies were ablated. No cancer recurrence was found
      in follow-up. Healing was associated with esophageal strictures in 58%, which
      were treated successfully by esophageal dilation in all patients. CONCLUSION:
      Photodynamic therapy combined with long-term acid inhibition provides an
      effective endoscopic therapy to (1) eliminate Barrett's mucosal dysplasia and
      superficial esophageal cancer and (2) reduce the amount of and, in some cases,
      eliminate Barrett's mucosa.

PMID- 9612189
TI  - Photodynamic therapy and the treatment of head and neck cancers.
AB  - Photodynamic therapy is an effective curative treatment for early carcinomas of
      the head and neck and may be of benefit as an adjuvant intraoperative therapy to
      increase cure rates of large head and neck tumors. Eighty-seven patients with
      neoplastic diseases of the larynx, oral cavity, pharynx, and skin have been
      treated with photodynamic therapy (PDT) with follow-up to 66 months. Patients
      with carcinoma-in-situ and T1 carcinomas obtained a complete response after one
      PDT treatment. All but two have remained free of disease. Ten patients with
      massive neck recurrences of squamous cell carcinomas were treated with
      intraoperative adjuvant PDT following tumor resection. Only three developed
      recurrence with 40-month follow-up, but only one recurrence was in the field of
      surgery and PDT.

PMID- 9612191
TI  - Photodynamic therapy of brain tumors.
AB  - Photodynamic therapy (PDT) for the treatment of a variety of brain tumors,
      particularly gliomas, has been extensively investigated in laboratory studies and
      has been studied in clinical trials. The main advantage of PDT lies in its
      ability to select out tumor cells that are infiltrating brain parenchyma and that
      are responsible for local tumor recurrence, the major therapeutic dilemma in the
      treatment of gliomas. PDT has been shown to be safe clinically but adequate
      trials have yet to be undertaken to prove its efficacy and much work remains to
      be done to optimize treatment. The laboratory studies and clinical trials
      involving PDT in the treatment of cerebral tumors, particularly the commonest
      brain tumors, gliomas, are discussed.

PMID- 9612192
TI  - Photodynamic therapy for malignant newly diagnosed supratentorial gliomas.
AB  - We report the use of photodynamic therapy (PDT) in the treatment of 20 patients
      with newly diagnosed malignant supratentorial gliomas. There were 10 males and 10
      females; their mean age was 56 years and the mean Karnofsky score was 75. Eleven
      patients had glioblastoma multiforme (GBM) and 9 had malignant astrocytoma (MA).
      Intravenous porphyrin photosensitizer was administered 12-36 h prior to surgery
      and photoillumination. At operation all patients had the tumor subtotally
      resected followed by intraoperative cavitary photoillumination. Interstitial
      photoillumination using fibers with 2-cm diffusing tips supplemented the cavitary
      illumination in 3 patients. The total light energy delivered ranged from 570 to
      4050 J (median = 1260 J). The energy density ranged from 15 to 110 J/cm2 (median
      = 32 J/cm2). All but two had postoperative radiation therapy (5000 cGy in 5
      weeks). No untoward effects of radiation in conjunction with PDT were identified.
      There was 1 postoperative death and 1 patient had a persistent increase in
      postoperative neurological deficit. The median survival of these 20 patients with
      newly diagnosed malignant gliomas was 44 weeks with a 1- and 2-year survival of
      40 and 15%, respectively. The median survival of these patients with newly
      diagnosed GBM was 37 weeks with a 1- and 2-year survival of 35 and 0%,
      respectively, and the median survival for MA was 48 weeks with a 1- and 2-year
      survival of 44 and 33%, respectively. Six patients with a Karnofsky score of > 70
      who received a light dose of > 1260 J (mean energy density = 62 +/- 20 SEM J/cm2)
      had a median survival of 92 weeks with a 1- and 2-year survival of 83 and 33%
      respectively. Patients with malignant astrocytic tumors (GBM and MA) have a very
      poor prognosis. Nevertheless PDT is safe in newly diagnosed patients with
      supratentorial malignant gliomas who undergo postoperative radiation and appears
      to prolong survival in selected patients when an adequate light dose is used.
      Further improvement in survival may be expected with higher light doses.

PMID- 9612193
TI  - Photodynamic therapy in the management of bladder cancer.
AB  - Photodynamic therapy (PDT) is primarily suggested for the therapy of papillary
      transitional cell carcinoma (TCC) and refractory carcinoma in situ (CIS), and
      prophylaxis of recurrent superficial TCC in those patients who have failed
      intravesical chemotherapy or immunotherapy. We reviewed our 13-year experience to
      assess the long-term role of PDT in the management of superficial bladder cancer,
      and propose a standard protocol. Fifty eight patients underwent a single PDT
      treatment with 1.5-2.0 mg/kg of Photofrin and 10-25 J/cm2 of light (630 nm). This
      single PDT treatment produced overall response rates of 84.2% in 19 patients with
      recurrent superficial papillary TCC, 80% in 20 patients with refractory CIS, and
      89.5% in 19 patients receiving prophylaxis. The PDT dose of 2.0 mg/kg and 15-25
      J/cm2 produced the most durable tumor response at the expense of severe local
      morbidity. However, the PDT dose of 1.5 mg/kg and 10-15 J/cm2 yielded variable
      tumor responses, with minimal local morbidity. Overall our data confirm that PDT
      is an effective therapy for superficial bladder cancer. We recommend PDT as a
      second line or immediate therapy for BCG or chemotherapy failures using a
      standard PDT dose of 1.5 mg/kg of Photofrin and 15 J/cm2 (630 nm) and a scheduled
      repeat treatment with 1.5 mg/kg and 10 J/cm2 at 6 and 12 months.

PMID- 9612194
TI  - Photodynamic therapy for cancer of the upper aerodigestive tract using tetra(m
      hydroxyphenyl)chlorin.
AB  - A major step in the development of photodynamic therapy (PDT) is the clinical
      optimization and evaluation of new photosensitizers (PS). Ideally, new compounds
      should be more effective and/or induce fewer side effects than the first
      generation PS such as hematoporphyrin derivative and Photofrin. We report the
      results of our study of PDT applied in the human upper aerodigestive tract, using
      tetra(m-hydroxyphenyl)chlorin (mTHPC) as the photosensitizing drug. Twenty-seven
      patients with early (i.e., in situ or microinvasive) squamous cell carcinomas and
      4 patients with T1 or T2 cancers were studied. In most cases, illumination of the
      tumor was performed 4 days after i.v. injection of 0.15 mg/kg of mTHPC using 652
      or 514 nm laser light. Of the 36 early tumors evaluated 30 (83%) showed no
      recurrence after a mean disease-free follow-up of 15.3 months (3-35 months). Of
      the T1 and T2 cancers, only one achieved a complete response. Major
      complications, all following red light illuminations, included 1 bronchial
      stenosis, 1 esophagotracheal fistula, and 2 probable occult perforations of the
      esophagus. PDT in the esophagus with green light renders such perforations
      essentially impossible, without, however, reducing the efficacy of the treatment.
      Skin photosensitization, never observed later than the first week after
      injection, was seen in 12 patients. In conclusion, photodynamic therapy with
      mTHPC is a safe and effective technique for the treatment of early carcinomas of
      the upper aerodigestive tract. Its efficacy is much lower for more advanced
      cancers.

PMID- 9612195
TI  - Photodynamic therapy (PDT) and photodiagnosis (PD) using endogenous
      photosensitization induced by 5-aminolevulinic acid (ALA): mechanisms and
      clinical results.
AB  - 5-Aminolevulinic acid (ALA), when added to many tissues, results in the
      accumulation of sufficient quantities of the endogenous photosensitizer
      protoporphyrin IX (PpIX) via the heme biosynthetic pathway, to produce a
      photodynamic effect when exposed to activating light. Therefore, ALA is the only
      photodynamic therapy (PDT) agent in current clinical development that is a
      biochemical precursor of a photosensitizer. Topical ALA application, followed by
      exposure to activating light (ALA PDT), has been reported effective for the
      treatment of a variety of dermatologic diseases including cutaneous superficial
      and nodular basal cell carcinoma, Bowen's disease, and actinic (solar) keratoses.
      Local internal application of ALA has also been used for selective endometrial
      ablation in animal model systems and in human clinical studies has shown
      selective formation of PpIX within the endometrium. PpIX induced by ALA
      application has also been used as a fluorescence detection marker for
      photodiagnosis (PD) of cancer and dysplastic conditions of the urinary bladder
      and other organs. Systemic, oral administration of ALA has been used for ALA PDT
      of superficial head and neck cancer, various gastrointestinal cancers, and the
      condition known as Barrett's esophagus. The current state of knowledge of the
      mechanisms of endogenous topical and systemic photosensitization using ALA, the
      results of published clinical trials, and possible methods of increasing the
      efficacy of endogenous photosensitization for ALA PDT are reviewed in this paper.

PMID- 9612196
TI  - Photodynamic therapy in veterinary medicine: current status and implications for
      applications in human disease.
AB  - The historical development and published veterinary applications of photodynamic
      therapy are reviewed. Potential animal models, using naturally-occurring diseases
      in veterinary patients, for the future development of photodynamic therapy are
      described.

PMID- 9612197
TI  - A preliminary pharmacokinetic study of intravenous Photofrin in patients.
AB  - Photofrin is a light-activated compound used for photodynamic therapy (PDT) of
      malignant tumors. Although PDT with this drug has been approved for clinical use
      in the United States, Canada, Japan, and the Netherlands there are few published
      reports on the biodistribution of Photofrin in humans. In this study we report
      measurable amounts of Photofrin in human serum up to approximately 1 year
      following injection of two different Photofrin doses. Concentration-time data
      were collected from 3, 12, 19, and 10 patients after 0.75, 0.875, 1, and 2 mg
      Photofrin/kg body weight. Patients who received 2 mg Photofrin/kg were scheduled
      to undergo intraoperative PDT for the treatment of mesothelioma or carcinoma of
      the lung. Patients receiving 0.75, 0.875, or 1 mg Photofrin/kg were treated for
      basal cell carcinoma; 1 mg Photofrin/kg is now a standard dose for PDT of
      cutaneous malignancies at this institute. For the 1 mg Photofrin/kg dose, a
      triexponential 3-compartment pharmacokinetic model was fitted to 30 data points
      pooled from the 19 patients, as if we had one "superpatient." The alpha, beta,
      and gamma halflives were approximately 16 h, 7.53 days, and 155.56 days,
      respectively. The mean (+/- SEM) serum concentrations 48 after injection (when
      most tumors are exposed to drug-activating light) of 0.875, 1, or 2 mg
      Photofrin/kg were 2.70 +/- 0.47, 4.00 +/- 0.66, and 3.47 +/- 0.97 micrograms
      Photofrin/ml, respectively. No porphyrin fluorescence could be detected in serum
      collected from patients 560 to 1335 days after Photofrin injection.

PMID- 9612199
TI  - Vascular effects of photodynamic therapy.
AB  - Vascular damage and blood flow stasis are consequences of photodynamic therapy
      (PDT) of solid tumors using many photosensitizers. Microvascular stasis and
      resulting hypoxia are effective means to produce cytotoxicity and tumor
      regression. The observation of blood flow stasis after photodynamic therapy
      results from a combination of damage to sensitive sites within the
      microvasculature and the resulting physiological responses to this damage. A
      generalized hypothesis for the mechanisms leading to vessel stasis begins with
      perturbation and damage to endothelial cells during light treatment of
      photosensitized tissues. Endothelial cell damage leads to the establishment of
      thrombogenic sites within the vessel lumen and this initiates a physiological
      cascade of responses including platelet aggregation, the release of vasoactive
      molecules, leukocyte adhesion, increases in vascular permeability, and vessel
      constriction. These effects from damage combine to produce blood flow stasis.

PMID- 9612198
TI  - Cellular targets and molecular responses associated with photodynamic therapy.
AB  - The positive clinical results associated with photodynamic therapy (PDT) have led
      to an expanded need to identify the cellular targets and molecular responses
      associated with this treatment. Increased knowledge regarding the mechanisms of
      action associated with PDT-mediated cytotoxicity should contribute to the
      continued advancement of this therapy. This report focuses on recent studies
      analyzing PDT resistance and examining stress protein and early response gene
      activation induced by photosensitizer mediated oxidative stress. Recurring
      observations from these studies indicate that subcellular targets and cellular
      responses associated with PDT can vary significantly for different
      photosensitizers.

PMID- 9612200
TI  - Induction of tumor immunity by photodynamic therapy.
AB  - The mechanism of tumor destruction by photodynamic therapy (PDT) incorporates a
      variety of events leading to inactivation of tumor cells. The unique feature of
      PDT is the mobilization of the host to participate in the eradication of treated
      cancer. A critical element is the induced inflammation at the treated site
      associated with massive invasion of activated myeloid cells. In addition to
      further destruction of cancer cells, conditions are created for the presentation
      of tumor antigens with subsequent activation of lymphoid cells, leading to tumor
      specific immunity. This inflammation-primed immune development process results in
      generation of tumor-specific immune memory cells that appear to be elicited
      against both strongly and poorly immunogenic PDT-treated cancers. Once generated
      by PDT, it is conceivable that these immune cells (especially if further expanded
      and activated by adjuvant immunotherapy) can be engaged in additional eradication
      of disseminated and/or metastatic lesions of the same cancer. A number of
      immunotherapy regimens have already been proven effective in enhancing the
      curative effect of PDT with various animal tumor models. Inflamed cancerous
      tissue at the PDT-treated site appears to exert powerful attracting signals for
      immune cells activated by different immunotherapy regimens.

PMID- 9612201
TI  - Photosensitizing potencies of the structural analogues of benzoporphyrin
      derivative in different biological test systems.
AB  - Benzoporphyrin derivative (BPD) is a potent photosensitizer in biological
      systems. There are four structural analogues of BPD. The analogues share the same
      chromophor, which results in their having almost identical optical spectra,
      extinction coefficients, and yields of singlet oxygen. Small structural
      differences affect their photosensitizing potency in various biological systems,
      and thus make them an interesting tool to study the structure-activity
      relationship. The ranking of the photosensitizing potency of the analogues
      differed depending on the test system. The more efficient photosensitization of
      tumor cell lines by the highly lipophilic monoacids as compared to that by less
      lipophilic diacids correlated positively with the partition coefficient, and was
      related to the rate of diffusion into the cells. However, in the assay systems
      where PDT targets were located in the membrane (red blood cells hemolysis,
      enveloped vesicular stomatitis virus, isolated mitochondria) there was very
      little difference in photosensitizing potency of BPD analogues. The results
      indicate that the evaluation of photosensitizers is affected by the test system
      and thus for photosensitizers screening purposes, the choice of the test system
      should be made based on the intended ultimate use.

PMID- 9612203
TI  - Laser literature watch.

PMID- 9612202
TI  - Phototherapy of cancer and atheromatous plaque with texaphyrins.
AB  - Cancer and cardiovascular disease are the leading causes of death in the western
      world. Photodynamic therapy (PDT) has demonstrated activity in the treatment of
      superficial cancerous lesions and as an intraoperative adjunct during surgical
      debulking. Texaphyrins are pure, synthetic water-soluble macrocycles that
      localize in both cancerous lesions and atheromatous plaque. Lutetium texaphyrin
      (PCI-0123) is activated by tissue-penetrating far red light (720-760 nm). Patient
      diagnosis and treatment planning is possible via magnetic resonance imaging (MRI)
      with the paramagnetic gadolinium texaphyrin (PCI-0120) or via fluorescence
      imaging using the diamagnetic PCI-0123. In this study it is shown that
      texaphyrins localize selectively in cancer and atheromatous plaque. PDT with PCI
      0123 is found to cause selective photodamage to the diseased tissue.
      Specifically, PCI-0123 acts to eradicate the SMT-F murine mammary tumors and diet
      induced atheromatous plaque in rabbits.

PMID- 9612204
TI  - A 310-bp minimal promoter mediates smooth muscle cell-specific expression of
      telokin.
AB  - A cell-specific promoter located in an intron of the smooth muscle myosin light
      chain kinase gene directs transcription of telokin exclusively in smooth muscle
      cells. Transgenic mice were generated in which a 310-bp rabbit telokin promoter
      fragment, extending from -163 to +147, was used to drive expression of simian
      virus 40 large T antigen. Smooth muscle-specific expression of the T-antigen
      transgene paralleled that of the endogenous telokin gene in all smooth muscle
      tissues except uterus. The 310-bp promoter fragment resulted in very low levels
      of transgene expression in uterus; in contrast, a transgene driven by a 2.4-kb
      fragment (-2250 to +147) resulted in high levels of transgene expression in
      uterine smooth muscle. Telokin expression levels correlate with the estrogen
      status of human myometrial tissues, suggesting that deletion of an estrogen
      response element (ERE) may account for the low levels of transgene expression
      driven by the 310-bp rabbit telokin promoter in uterine smooth muscle.
      Experiments in A10 smooth muscle cells directly showed that reporter gene
      expression driven by the 2.4-kb, but not 310-bp, promoter fragment could be
      stimulated two- to threefold by estrogen. This stimulation was mediated through
      an ERE located between -1447 and -1474. Addition of the ERE to the 310-bp
      fragment restored estrogen responsiveness in A10 cells. These data demonstrate
      that in addition to a minimal 310-bp proximal promoter at least one distal cis
      acting regulatory element is required for telokin expression in uterine smooth
      muscle. The distal element may include an ERE between -1447 and -1474.

PMID- 9612205
TI  - Diversity of Ca(2+)-mobilizing mechanisms focus on "cGMP-mediated Ca2+ release
      from IP3-insensitive Ca2+ stores in smooth muscle".

PMID- 9612206
TI  - cGMP-mediated Ca2+ release from IP3-insensitive Ca2+ stores in smooth muscle.
AB  - Recent studies on the role of nitric oxide (NO) in gastrointestinal smooth muscle
      have raised the possibility that NO-stimulated cGMP could, in the absence of cGMP
      dependent protein kinase (PKG) activity, act as a Ca(2+)-mobilizing messenger [K.
      S. Murthy, K.-M. Zhang, J.-G. f1p4 J. T. Grider, and G. M. Makhlouf. Am. J.
      Physiol. 265 (Gastrointest. Liver Physiol. 28): G660-G671, 1993]. This notion was
      examined in dispersed gastric smooth muscle cells with 8-bromo-cGMP (8-BrcGMP)
      and with NO and vasoactive intestinal peptide (VIP), which stimulate endogenous
      cGMP. In muscle cells treated with cAMP-dependent protein kinase (PKA) and PKG
      inhibitors (H-89 and KT-5823), 8-BrcGMP (10 microM), NO (1 microM), and VIP (1
      microM) stimulated 45Ca2+ release (21 +/- 3 to 30 +/- 1% decrease in 45Ca2+ cell
      content); Ca2+ release stimulated by 8-BrcGMP was concentration dependent with an
      EC50 of 0.4 +/- 0.1 microM and a threshold of 10 nM. 8-BrcGMP and NO increased
      cytosolic free Ca2+ concentration ([Ca2+]i) and induced contraction; both
      responses were abolished after Ca2+ stores were depleted with thapsigargin. With
      VIP, which normally increases [Ca2+]i by stimulating Ca2+ influx, treatment with
      PKA and PKG inhibitors caused a further increase in [Ca2+]i that reverted to
      control levels in cells pretreated with thapsigargin. Neither Ca2+ release nor
      contraction induced by cGMP and NO in permeabilized muscle cells was affected by
      heparin or ruthenium red. Ca2+ release induced by maximally effective
      concentrations of cGMP and inositol 1,4,5-trisphosphate (IP3) was additive,
      independent of which agent was applied first. We conclude that, in the absence of
      PKA and PKG activity, cGMP stimulates Ca2+ release from an IP3-insensitive store
      and that its effect is additive to that of IP3.

PMID- 9612207
TI  - Serum deprivation induces a unique hypercontractile phenotype of cultured smooth
      muscle cells.
AB  - Chronic asthma is characterized by hypertrophy and hyperplasia of airway smooth
      muscle cells (SMC) that limit airflow by a geometric effect. Whether
      contractility of airway SMC is altered is not clear. Cultured cells were used as
      a model of hyperplasia. Phenotypic changes seen indicated conversion to a
      synthetic, weakly contractile type. At confluence, although limited reversal of
      protein changes was seen, no restoration in contractility occurred. Phenotypic
      modulation of postconfluent cultured airway SMC under prolonged serum deprivation
      (arrested cells) is reported here. Two phenotypically distinct groups of cells
      were identified in primary airway SMC cultures: 1) elongated spindle-shaped
      cells, which expressed large amounts of smooth muscle contractile and regulatory
      proteins, and 2) flat and stellate cells, which expressed very little. The first
      group showed a surprising shortening capacity and a velocity that was even
      greater than that of the freshly isolated cells, whereas the second group became
      spherical and noncontractile. Even more surprising was that the myosin heavy
      chain (MHC) isoform (SM-B) generally said to be associated with the higher
      shortening velocity disappeared from the cell, while the content of the key rate
      limiting regulating enzyme, myosin light chain kinase (MLCK), increased 30-fold.
      We conclude that a functional, contractile phenotype of airway SMC can be
      obtained by prolonged serum deprivation. We speculate that the increased
      contractility could be the result of increased phosphorylation of the 20-kDa
      myosin light chain resulting from increased content of smooth muscle MLCK rather
      than any increase in endogenous MHC ATPase activity. This model may be useful for
      study of SMC differentiation and contraction.

PMID- 9612208
TI  - Human Na(+)-myo-inositol cotransporter gene: alternate splicing generates diverse
      transcripts.
AB  - Na(+)-myo-inositol cotransport activity generally maintains millimolar
      intracellular concentrations of myo-inositol and specifically promotes
      transepithelial myo-inositol transport in kidney, intestine, retina, and choroid
      plexus. Glucose-induced, tissue-specific myo-inositol depletion and impaired
      Na(+)-myo-inositol cotransport activity are implicated in the pathogenesis of
      diabetic complications, a process modeled in vitro in cultured human retinal
      pigment epithelium (RPE) cells. To explore this process at the molecular level, a
      human RPE cDNA library was screened with a canine Na(+)-dependent myo-inositol
      cotransporter (SMIT) cDNA. Overlapping cDNAs spanning 3569 nt were cloned. The
      resulting cDNA sequence contained a 2154-nt open reading frame, 97% identical to
      the canine SMIT amino acid sequence. Genomic clones containing SMIT exons
      suggested that the cDNA is derived from at least five exons. Hypertonic stress
      induced a time-dependent increase, initially in a 16-kb transcript and
      subsequently in 11.5-, 9.8-, 8.5-, 3.8-, and approximately 1.2-kb SMIT
      transcripts, that was ascribed to alternate exon splicing using exon-specific
      probes and direct cDNA sequencing. The human SMIT gene is a complex multiexon
      transcriptional unit that by alternate exon splicing generates multiple SMIT
      transcripts that accumulate differentially in response to hypertonic stress.

PMID- 9612209
TI  - Contractile activity is required for sarcomeric assembly in phenylephrine-induced
      cardiac myocyte hypertrophy.
AB  - Agonist-induced hypertrophy of cultured neonatal rat ventricular myocytes (NRVM)
      has been attributed to biochemical signals generated during receptor activation.
      However, NRVM hypertrophy can also be induced by spontaneous or electrically
      stimulated contractile activity in the absence of exogenous neurohormonal
      stimuli. Using single-cell imaging of fura 2-loaded myocytes, we found that low
      density, noncontracting NRVM begin to generate intracellular Ca2+ concentration
      ([Ca2+]i) transients and contractile activity within minutes of exposure to the
      alpha 1-adrenergic agonist phenylephrine (PE; 50 microM). However, NRVM
      pretreated with verapamil and then stimulated with PE failed to elicit [Ca2+]i
      transients and beating. We therefore examined whether PE-induced [Ca2+]i
      transients and contractile activity were required to elicit specific aspects of
      the hypertrophic phenotype. PE treatment (48-72 h) increased cell size, total
      protein content, total protein-to-DNA ratio, and myosin heavy chain (MHC)
      isoenzyme content. PE also stimulated sarcomeric protein assembly and prolonged
      MHC half-life. However, blockade of voltage-gated L-type Ca2+ channels with
      verapamil, diltiazem, or nifedipine (10 microM) blocked PE-induced total protein
      and MHC accumulation and prevented the time-dependent assembly of myofibrillar
      proteins into sarcomeres. Inhibition of actin-myosin cross-bridge cycling with
      2,3-butanedione monoxime (7.5 mM) also prevented PE-induced total protein and MHC
      accumulation, indicating that mechanical activity, rather than [Ca2+]i transients
      per se, was required. In contrast, blockade of [Ca2+]i transients and contractile
      activity did not prevent the PE-induced increase in cell surface area, activation
      of the mitogen-activated protein kinases ERK1 and ERK2, or upregulation of atrial
      natriuretic factor gene expression. Thus contractile activity is required to
      elicit some but not all aspects of the the hypertrophic phenotype induced by
      alpha 1-adrenergic receptor activation.

PMID- 9612210
TI  - Increased prostacyclin and PGE2 stimulated cAMP production by macrophages from
      endotoxin-tolerant rats.
AB  - Sublethal administration of lipopolysaccharide (LPS) renders rats tolerant to
      multiple lethal stimuli. Tolerant macrophages exhibit differential alterations in
      LPS-stimulated cytokine and inflammatory mediator release. Increased cAMP levels
      stimulated by PGE2 or prostacyclin (PGI2) result in differential effects on LPS
      induced cytokine release and protect against the pathophysiological changes of
      endotoxemia. In the present studies, we sought to determine whether PGE2- and
      PGI2-stimulated cAMP levels are altered in tolerant macrophages. Incubation of
      macrophages with cicaprost or 11-deoxy-PGE1 in the presence of phosphodiesterase
      inhibitors resulted in significantly higher (2.5- to 6.5-fold) cAMP
      concentrations in tolerant macrophages compared with control. In contrast,
      isoproterenol-stimulated cAMP levels were not significantly different between
      control and tolerant cells. Also, incubation of tolerant macrophages with LPS did
      not result in significantly elevated cAMP levels. Prostacyclin (IP) receptor mRNA
      levels were significantly increased in tolerant cells compared with controls,
      whereas [3H]PGE2 binding and PGE2 EP4 receptor mRNA levels were not significantly
      changed. These studies suggest that LPS tolerance induces selective alterations
      in eicosanoid regulation of cAMP formation.

PMID- 9612211
TI  - A second enzyme protecting mineralocorticoid receptors from glucocorticoid
      occupancy.
AB  - We have confirmed that A6 cells (derived from kidney of Xenopus laevis), which
      contain both mineralocorticoid and glucocorticoid receptors, do not normally
      possess 11 beta-hydroxysteroid dehydroxgenase (11 beta-HSD1 or 11 beta-HSD2)
      enzymatic activity and so are without apparent "protective" enzymes. A6 cells do
      not convert the glucocorticoid corticosterone to 11-dehydrocorticosterone but do,
      however, possess steroid 6 beta-hydroxylase that transforms corticosterone to 6
      beta-hydroxycorticosterone. This hydroxylase is cytochrome P-450 3A (CYP3A). We
      have now determined the effects of 3 alpha,5 beta-tetrahydroprogesterone and
      chenodeoxycholic acid (both inhibitors of 11 beta-HSD1) and 11
      dehydrocorticosterone and 11 beta-hydroxy-3 alpha,5 beta-tetrahydroprogesterone
      (inhibitors of 11 beta-HSD2) and carbenoxalone, which inhibits both 11 beta-HSD1
      and 11 beta-HSD2, on the actions and metabolism of corticosterone and active Na+
      transport [short-circuit current (Isc)] in A6 cells. All of these 11 beta-HSD
      inhibitory substances induced a significant increment in corticosterone-induced
      Isc, which was detectable within 2 h. However, none of these agents caused an
      increase in Isc when incubated by themselves with A6 cells. In all cases, the
      additional Isc was inhibited by the mineralocorticoid receptor (MR) antagonist,
      RU-28318, whereas the original Isc elicited by corticosterone alone was inhibited
      by the glucocorticoid receptor antagonist, RU-38486. In separate experiments,
      each agent was shown to significantly inhibit metabolism of corticosterone to 6
      beta-hydroxycorticosterone in A6 cells, and a linear relationship existed between
      6 beta-hydroxylase inhibition and the MR-mediated increase in Isc in the one
      inhibitor tested. Troleandomycin, a selective inhibitor of CYP3A, inhibited 6
      beta-hydroxylase and also significantly enhanced corticosterone-induced Isc at 2
      h. These experiments indicate that the enhanced MR-mediated Isc in A6 cells may
      be related to inhibition of 6 beta-hydroxylase activity in these cells and that
      this 6 beta-hydroxylase (CYP3A) may be protecting the expression of
      corticosterone-induced active Na+ transport in A6 cells by MR-mediated
      mechanism(s).

PMID- 9612212
TI  - Effect of phorbol esters on Ca2+ sensitivity and myosin light-chain
      phosphorylation in airway smooth muscle.
AB  - We studied in beta-escin-permeabilized canine tracheal smooth muscle (CTSM) the
      effect of the protein kinase C (PKC) agonist phorbol 12,13-dibutyrate (PDBu) on
      isometric force at a constant submaximal Ca2+ concentration (i.e., the effect on
      Ca2+ sensitivity) and regulatory myosin light-chain (rMLC) phosphorylation. PDBu
      increased Ca2+ sensitivity, an increase associated with a concentration
      dependent, sustained increase in rMLC phosphorylation. PDBu altered the
      relationship between rMLC phosphorylation and isometric force such that the
      increase in isometric force was less than that expected for the increase in rMLC
      phosphorylation observed. The effect of four PKC inhibitors [calphostin C,
      chelerythrine chloride, a pseudosubstrate inhibitor for PKC, PKC peptide-(19-31)
      (PSSI), and staurosporine] on PDBu-induced Ca2+ sensitization as well as the
      effect of calphostin C and PSSI on rMLC phosphorylation were determined. Whereas
      none of these compounds prevented or reversed the PDBu-induced increase in Ca2+
      sensitivity, the PDBu-induced increase in rMLC phosphorylation was inhibited. We
      conclude that PDBu increases rMLC phosphorylation by activation of PKC but that
      the associated PDBu-induced increases in Ca2+ sensitivity are mediated by
      mechanisms other than activation of PKC in permeabilized airway smooth muscle.

PMID- 9612213
TI  - Quantitative contribution of NHE2 and NHE3 to rabbit ileal brush-border Na+/H+
      exchange.
AB  - Intestinal neutral NaCl absorption, which is made up of brush-border (BB) Na+/H+
      exchange linked to BB Cl-/HCO3- exchange, is up- and downregulated as part of
      digestion and diarrheal diseases. Glucocorticoids stimulate ileal NaCl absorption
      and BB Na+/H+ exchange. Intestinal BB contains two Na+/H+ exchanger isoforms,
      NHE2 and NHE3, but their relative roles in rabbit ileal BB Na+/H+ exchange has
      not been determined. A technique to separate the contribution of NHE2 and NHE3 to
      ileal BB Na+/H+ exchange activity was standardized by using an amiloride-related
      compound, HOE-694. Under basal conditions, both NHE2 and NHE3 contribute
      approximately 50% to ileal Na+/H+ exchange. Glucocorticoids (methylprednisolone)
      increase BB Na+/H+ exchange (2.5 times) but increase only ileal NHE3 activity
      (4.1 times), without an effect on NHE2 activity. Thus ileal BB Na+/H+ exchange in
      animals treated with glucocorticoids is 69% via NHE3. A quantitative Western
      analysis for NHE3 was developed, using as an internal standard a fusion protein
      of the COOH-terminal 85 amino acids of NHE3 and maltose binding protein.
      Glucocorticoid treatment increased the amount of BB NHE3. The quantitative
      Western analysis showed that NHE3 makes up 0.018% of ileal BB protein in control
      rabbits and 0.042% (2.3 times as much) in methylprednisolone-treated rabbits.
      Methylprednisolone treatment did not alter the amount of ileal BB NHE2 protein.
      NHE3 turnover number was estimated to be 458 cycles/s under basal conditions and
      708 cycles/s in glucocorticoid-treated ileum. Thus methylprednisolone stimulates
      ileal BB Na+/H+ exchange activity only by an effect on NHE3 and not on NHE2; it
      does so primarily by increasing the amount of BB NHE3, although it also increases
      the NHE3 turnover number.

PMID- 9612214
TI  - Basis for late rise in fura 2 R signal reporting [Ca2+]i during relaxation in
      intact rat ventricular trabeculae.
AB  - Intact rat ventricular trabeculae were injected with the salt form of fura 2, and
      the fura 2 ratio signal (R) was used to report intracellular Ca2+ concentration
      ([Ca2+]i). The fixed end relaxation phase of a twitch is associated with a
      slowing of the decay of the R signal, or even a reversal, to form a distinct
      bump, indicating a transient rise in [Ca2+]i. The bump is most prominent at 30
      degrees C, and motion artifact is not its cause. Increasing doses of 2,3
      butanedione monoxime caused progressive attenuation of the twitch and bump.
      Increasing the bathing Ca2+ concentration potentiated the twitch and enhanced the
      bump. Imposed muscle shortening during relaxation caused a much quicker force
      decline, and this led to the appearance of a much more prominent associated bump.
      The amplitude of the bump depends on the amplitude of twitch force and the rate
      of relaxation. These findings can be explained, as in skeletal muscle, by making
      cross-bridge attachment and Ca2+ binding to troponin C strongly cooperative;
      therefore, the bump during fast relaxation is produced by a reversal of this
      cooperatively, leading to rapid dissociation of Ca2+ from troponin C into the
      myoplasm.

PMID- 9612215
TI  - Is cytoskeletal tension a major determinant of cell deformability in adherent
      endothelial cells?
AB  - We tested the hypothesis that mechanical tension in the cytoskeleton (CSK) is a
      major determinant of cell deformability. To confirm that tension was present in
      adherent endothelial cells, we either cut or detached them from their basal
      surface by a microneedle. After cutting or detachment, the cells rapidly
      retracted. This retraction was prevented, however, if the CSK actin lattice was
      disrupted by cytochalasin D (Cyto D). These results confirmed that there was
      preexisting CSK tension in these cells and that the actin lattice was a primary
      stress-bearing component of the CSK. Second, to determine the extent to which
      that preexisting CSK tension could alter cell deformability, we developed a
      stretchable cell culture membrane system to impose a rapid mechanical distension
      (and presumably a rapid increase in CSK tension) on adherent endothelial cells.
      Altered cell deformability was quantitated as the shear stiffness measured by
      magnetic twisting cytometry. When membrane strain increased 2.5 or 5%, the cell
      stiffness increased 15 and 30%, respectively. Disruption of actin lattice with
      Cyto D abolished this stretch-induced increase in stiffness, demonstrating that
      the increased stiffness depended on the integrity of the actin CSK.
      Permeabilizing the cells with saponin and washing away ATP and Ca2+ did not
      inhibit the stretch-induced stiffening of the cell. These results suggest that
      the stretch-induced stiffening was primarily due to the direct mechanical changes
      in the forces distending the CSK but not to ATP- or Ca(2+)-dependent processes.
      Taken together, these results suggest preexisting CSK tension is a major
      determinant of cell deformability in adherent endothelial cells.

PMID- 9612216
TI  - Neuropeptide Y inhibition of calcium channels in PC-12 pheochromocytoma cells.
AB  - We previously demonstrated, using rat PC-12 pheochromocytoma cells differentiated
      to a sympathetic neuronal phenotype with nerve growth factor (NGF), that
      neuropeptide Y (NPY) inhibits catecholamine synthesis as well as release. Inquiry
      into the mechanisms of these inhibitions implicated distinct pathways involving
      reduction of Ca2+ influx through voltage-activated Ca2+ channels. In the present
      investigation the effects of NPY on whole cell Ba2+ currents were examined to
      obtain direct evidence supporting the mechanisms suggested by those studies. NPY
      was found to inhibit the voltage-activated Ba2+ current in NGF-differentiated PC
      12 cells in a reversible fashion with an EC50 of 13 nM. This inhibition was
      pertussis toxin sensitive and resulted from NPY modulation of L- and N-type Ca2+
      channels. The inhibition of L-type channels was not seen with < 1 nM free
      intracellular Ca2+ or when protein kinase C (PKC) was inhibited by chelerythrine
      or PKC-(19-31). Furthermore, the effect of NPY on L-type channels was mimicked by
      the PKC activator phorbol 12-myristate 13-acetate. These studies demonstrate
      that, in addition to inhibition of N-type Ca2+ channels, in NGF-differentiated PC
      12 cells NPY inhibits L-type Ca2+ channels via an intracellular Ca(2+)- and PKC
      dependent pathway.

PMID- 9612217
TI  - Structure and in vitro function of human subcutaneous small arteries in mild
      heart failure.
AB  - The structure and function of subcutaneous small arteries from patients with mild
      heart failure (n = 27) 6-43 mo after myocardial infarction were compared with
      vessels from healthy control subjects (n = 10). Patients were randomized to
      treatment with placebo or the angiotensin-converting enzyme inhibitor ramipril
      starting 3-10 days after myocardial infarction. Dissected arterial vessels were
      mounted on a wire myograph for measurement of morphology and isometric tension.
      Morphology was not different in arteries from the three groups. Responses to
      norepinephrine, angiotensin II, and electrical field stimulation were similar in
      arteries from placebo-treated patients with mild heart failure and control
      subjects. Similarly, endothelium-dependent and -independent relaxation was normal
      in arteries from patients with mild heart failure. Ramipril therapy was
      associated with functional alterations: vasoconstrictor responses to
      norepinephrine and angiotensin II were significantly enhanced compared with
      placebo (P < 0.001). These data suggest that vascular structure and function are
      not different in vitro in subcutaneous arteries from placebo-treated patients
      with mild heart failure. Angiotensin-converting enzyme inhibitor therapy is
      associated with enhanced vasoconstriction to norepinephrine and angiotensin II,
      which may reflect upregulation of receptor-mediated events.

PMID- 9612218
TI  - Milrinone inhibits contractility in skinned skeletal muscle fibers.
AB  - Direct action of the cardiotonic bipyridine milrinone on the cross bridges of
      single fibers of skinned rabbit skeletal muscle was investigated. At 10 degrees C
      and pH 7.0, milrinone reduced isometric tension in a logarithmically
      concentration-dependent manner, with a 55% reduction in force at 0.6 mM.
      Milrinone also reduced Ca2+ sensitivity of skinned fibers in terms of force
      production; the shift in the force-pCa curve indicated a change in the pCa value
      at 50% maximal force from 6.10 to 5.94. The unloaded velocity of shortening was
      reduced by 18% in the presence of 0.6 mM milrinone. Parts of the transient
      tension response to step change in length were altered by milrinone, so that the
      test and control transients could not be superimposed. The results indicate that
      milrinone interferes with the cross-bridge cycle and possibly detains cross
      bridges in low-force states. The results also suggest that the positive inotropic
      effect of milrinone on cardiac muscle is probably not due to the drug's direct
      action on the muscle cross bridges. The specific and reversible action of the
      bipyridine on muscle cross bridges makes it a potentially useful tool for probing
      the chemomechanical cross-bridge cycle.

PMID- 9612219
TI  - 5' heterogeneity in epithelial sodium channel alpha-subunit mRNA leads to
      distinct NH2-terminal variant proteins.
AB  - The amiloride-sensitive epithelial sodium channel (ENaC) is composed of three
      subunits: alpha, beta, and gamma. The human alpha-ENaC subunit is expressed as at
      least two transcripts (N. Voilley, E. Lingueglia, G. Champigny, M. G. Mattei, R.
      Waldmann, M. Lazdunski, and P. Barbry. Proc. Natl. Acad. Sci. USA 91: 247-251,
      1994). To determine the origin of these transcripts, we characterized the 5' end
      of the alpha-ENaC gene. Four transcripts that differ at their first exon were
      identified. Exon 1A splices to exon 2 to form the 5' end of alpha-ENaC1, whereas
      exon 1B arises separately and continues into exon 2 to form alpha-ENaC2. Other
      variant mRNAs, alpha-ENaC3 and alpha-ENaC4, are formed by activating 5' splice
      sites within exon 1B. Although alpha-ENaC3 and -4 did not change the open reading
      frame for alpha-ENaC, alpha-ENaC2 contains upstream ATGs that add 59 amino acids
      to the previous (alpha-ENaC1) protein. To address the significance of these
      isoforms, both proteins were expressed in Xenopus oocytes. The cRNA for each
      alpha-ENaC transcript when combined with beta- and gamma-ENaC cRNA reconstituted
      a low-conductance ion channel with amiloride-sensitive currents of similar
      characteristics. We have thus identified variant alpha-ENaC mRNAs that lead to
      functional ENaC peptides.

PMID- 9612220
TI  - Modulation of human neuronal alpha 1E-type calcium channel by alpha 2 delta
      subunit.
AB  - Calcium channels are composed of a pore-forming subunit, alpha 1, and at least
      two auxiliary subunits, beta- and alpha 2 delta-subunits. It is well known that
      beta-subunits regulate most of the properties of the channel. The function of
      alpha 2 delta-subunit is less understood. In this study, the effects of the
      calcium channel alpha 2 delta-subunit on the neuronal alpha 1E voltage-gated
      calcium channel expressed in Xenopus oocytes was investigated without and with
      simultaneous coexpression of either the beta 1b- or the beta 2a-subunit. Most
      aspects of alpha 1E function were affected by alpha 2 delta. Thus alpha 2 delta
      caused a shift in the current-voltage and conductance-voltage curves toward more
      positive potentials and accelerated activation, deactivation, and the
      installation of the inactivation process. In addition, the efficiency with which
      charge movement is coupled to pore opening assessed by determining ratios of
      limiting conductance to limiting charge movement was decreased by alpha 2 delta
      by factors that ranged from 1.6 (P < 0.01) for alpha 1E-channels to 3.0 (P <
      0.005) for alpha 1E beta 1b-channels. These results indicate that alpha 2 delta
      facilitates the expression and the maturation of alpha 1E-channels and converts
      these channels into molecules responding more rapidly to voltage.

PMID- 9612221
TI  - Aquaporins in complex tissues: distribution of aquaporins 1-5 in human and rat
      eye.
AB  - Multiple physiological fluid movements are involved in vision. Here we define the
      cellular and subcellular sites of aquaporin (AQP) water transport proteins in
      human and rat eyes by immunoblotting, high-resolution immunocytochemistry, and
      immunoelectron microscopy. AQP3 is abundant in bulbar conjunctival epithelium and
      glands but is only weakly present in corneal epithelium. In contrast, AQP5 is
      prominent in corneal epithelium and apical membranes of lacrimal acini. AQP1 is
      heavily expressed in scleral fibroblasts, corneal endothelium and keratocytes,
      and endothelium covering the trabecular meshwork and Schlemm's canal. Although
      AQP1 is plentiful in ciliary nonpigmented epithelium, it is not present in
      ciliary pigmented epithelium. Posterior and anterior epithelium of the iris and
      anterior lens epithelium also contain significant amounts of AQP1, but AQP0
      (major intrinsic protein of the lens) is expressed in lens fiber cells. Retinal
      Muller cells and astrocytes exhibit notable concentrations of AQP4, whereas
      neurons and retinal pigment epithelium do not display aquaporin immunolabeling.
      These studies demonstrate selective expression of AQP1, AQP3, AQP4, and AQP5 in
      distinct ocular epithelia, predicting specific roles for each in the complex
      network through which water movements occur in the eye.

PMID- 9612222
TI  - Frequency modulation of Ca2+ sparks is involved in regulation of arterial
      diameter by cyclic nucleotides.
AB  - Forskolin, which elevates cAMP levels, and sodium nitroprusside (SNP) and
      nicorandil, which elevate cGMP levels, increased, by two- to threefold, the
      frequency of subcellular Ca2+ release ("Ca2+ sparks") through ryanodine-sensitive
      Ca2+ release (RyR) channels in the sarcoplasmic reticulum (SR) of myocytes
      isolated from cerebral and coronary arteries of rats. Forskolin, SNP, nicorandil,
      dibutyryl-cAMP, and adenosine increased the frequency of Ca(2+)-sensitive K+
      (KCa) currents ["spontaneous transient outward currents" (STOCs)] by two- to
      threefold, consistent with Ca2+ sparks activating STOCs. These agents also
      increased the mean amplitude of STOCs by 1.3-fold, an effect that could be
      explained by activation of KCa channels, independent of effects on Ca2+ sparks.
      To test the hypothesis that cAMP could act to dilate arteries through activation
      of the Ca2+ spark-->KCa channel pathway, the effects of blockers of KCa channels
      (iberiotoxin) and of Ca2+ sparks (ryanodine) on forskolin-induced dilations of
      pressurized cerebral arteries were examined. Forskolin-induced dilations were
      partially inhibited by iberiotoxin and ryanodine (with no additive effects) and
      were entirely prevented by elevating external K+. Forskolin lowered average Ca2+
      in pressurized arteries while increasing ryanodine-sensitive, caffeine-induced
      Ca2+ transients. These experiments suggest a new mechanism for cyclic nucleotide
      mediated dilations through an increase in Ca2+ spark frequency, caused by effects
      on SR Ca2+ load and possibly on the RyR channel, which leads to increased STOC
      frequency, membrane potential hyperpolarization, closure of voltage-dependent
      Ca2+ channels, decrease in arterial wall Ca2+, and, ultimately, vasodilation.

PMID- 9612223
TI  - In vitro and in vivo evaluation of insulin-producing beta TC6-F7 cells in
      microcapsules.
AB  - In the present study, the insulin secretory capacity of beta TC6-F7 cells in
      microcapsules was evaluated. The cell mass within capsules was found to expand in
      a three-dimensional fashion, in contrast to cells seeded on plates that grew as a
      monolayer. In in vitro studies, both free and encapsulated cells were found to
      secrete insulin in the absence of glucose, at 13.6 +/- 1.1 and 14.5 +/- 0.9
      ng.10(6) cells-1.60 min-1, respectively, with the response rising to a maximum of
      26.0 +/- 0.8 and 31 +/- 2.3 ng.10(6) cells-1.60 min-1 in the presence of 16.8 mM
      glucose. Encapsulated cells were able to produce Ca2+ responses in the presence
      of KCl (50 mM) and BAY K 8644 (100 microM). In in vivo studies, intraperitoneal
      transplantation of 3.0 x 10(6) microencapsulated cells into mice (n = 5) with
      streptozotocin-induced diabetes resulted in the restoration of normoglycemia up
      to 57 days. Insulin concentrations rose from 0.4 +/- 0.1 ng/ml before the graft
      administration to 2.2 +/- 0.8 ng/ml after the transplantation in the
      normoglycemic recipients. An oral glucose challenge in transplant recipients
      demonstrated a flat glucose response, suggesting extremely high glucose clearance
      rates. These data demonstrate the potential use of the immunoisolated beta-cell
      lines for the treatment of diabetes.

PMID- 9612224
TI  - Dying enterocytes downregulate signaling pathways converging on Ras: rescue by
      protease inhibition.
AB  - Organ and cell cultures of the small intestine serve as excellent in vitro models
      for programmed cell death (PCD). Cells cultured in serum-free, minimal medium
      rapidly died, as evidenced by histological changes, internucleosomal DNA
      cleavage, and TdT-mediated dUTP nick end labeling. Cell death was pervasive,
      although nonepithelial cells within the fibrovascular villus core were spared.
      PCD did not require a functional p53 gene. Serine and cysteine protease
      inhibitors, but not FCS, suppressed it. Relative to structural and functional
      proteins, dying enterocytes rapidly downregulated Ras-convergent proteins,
      including epidermal growth factor receptor, Erb-B2, and the son of sevenless
      guanine nucleotide exchangers. Reductions in the steady-state levels of both
      protein and mRNA were observed. These reductions were prevented by a combination
      of death-defying serine and caspase inhibitors, indicating a requirement for the
      initiation of death. Thus, during catastrophic PCD, intestinal epithelial cells
      delete cell surface signaling pathways responsible for Ras activation.

PMID- 9612225
TI  - Hormonal regulation of ENaCs: insulin and aldosterone.
AB  - Although a variety of hormones and other agents modulate renal Na+ transport
      acting by way of the epithelial Na+ channel (ENaC), the mode(s), pathways, and
      their interrelationships in regulation of the channel remain largely unknown. It
      is likely that several hormones may be present concurrently in vivo, and it is,
      therefore, important to understand potential interactions among the various
      regulatory factors as they interact with the Na+ transport pathway to effect
      modulation of Na+ reabsorption in distal tubules and other native tissues. This
      study represents specifically a determination of the interaction between two
      hormones, namely, aldosterone and insulin, which stimulate Na+ transport by
      entirely different mechanisms. We have used a noninvasive pulse protocol of
      blocker-induced noise analysis to determine changes in single-channel current
      (iNa), channel open probability (Po), and functional channel density (NT) of
      amiloride-sensitive ENaCs at various time points following treatment with insulin
      for 3 h of unstimulated control and aldosterone-pretreated A6 epithelia.
      Independent of threefold differences of baseline values of transport caused by
      aldosterone, 20 nM insulin increased by threefold and within 10-30 min the
      density of the pool of apical membrane ENaCs (NT) involved in transport. The very
      early (10 min) increases of channel density were accompanied by relatively small
      decreases of iNa (10-20%) and decreases of p.o. (28%) in the aldosterone
      pretreated tissues but not the control unstimulated tissues. The early changes of
      iNa, p.o., and NT were transient, returning very slowly over 3 h toward their
      respective control values at the time of addition of insulin. We conclude that
      aldosterone and insulin act independently to stimulate apical Na+ entry into the
      cells of A6 epithelia by increase of channel density.

PMID- 9612226
TI  - Contractile activity-induced adaptations in the mitochondrial protein import
      system.
AB  - We previously demonstrated that subsarcolemmal (SS) and intermyofibrillar (IMF)
      mitochondrial subfractions import proteins at different rates. This study was
      undertaken to investigate 1) whether protein import is altered by chronic
      contractile activity, which induces mitochondrial biogenesis, and 2) whether
      these two subfractions adapt similarly. Using electrical stimulation (10 Hz, 3
      h/day for 7 and 14 days) to induce contractile activity, we observed that malate
      dehydrogenase import into the matrix of the SS and IMF mitochondia isolated from
      stimulated muscle was significantly increased by 1.4-to 1.7-fold, although the
      pattern of increase differed for each subfraction. This acceleration of import
      may be mitochondrial compartment specific, since the import of Bcl-2 into the
      outer membrane was not affected. Contractile activity also modified the
      mitochondrial content of proteins comprising the import machinery, as evident
      from increases in the levels of the intramitochondrial chaperone mtHSP70 as well
      as the outer membrane import receptor Tom20 in SS and IMF mitochondria. Addition
      of cytosol isolated from stimulated or control muscles to the import reaction
      resulted in similar twofold increases in the ability of mitochondria to import
      malate dehydrogenase, despite elevations in the concentration of mitochondrial
      import-stimulating factor within the cytosol of chronically stimulated muscle.
      These results suggest that chronic contractile activity modifies the extra- and
      intramitochondrial environments in a fashion that favors the acceleration of
      precursor protein import into the matrix of the organelle. This increase in
      protein import is likely an important adaptation in the overall process of
      mitochondrial biogenesis.

PMID- 9612227
TI  - Chronic exposure to TPA depletes PKC alpha and augments Ca-dependent insulin
      secretion from cultured rat islets.
AB  - The insulin secretory responses of rat islets to glucose (15 mM), 12-O
      tetradecanoylphorbol 13-acetate (TPA; 500 nM), and potassium (30 mM) were
      determined from perifused islets cultured for 22-24 h in CMRL-1066 medium
      (control cultured) or islets cultured in the additional presence of 500 nM TPA.
      Islet content of protein kinase C alpha (PKC alpha) and serine and threonine
      phosphoprotein patterns were also monitored after the culture period. Compared
      with freshly isolated islets, culturing alone had no adverse effect on the
      capacity of TPA or 30 mM potassium to stimulate secretion or on the islet content
      of PKC alpha. In agreement with previous studies, culturing in TPA reduced the
      islet content of immunoreactive PKC alpha by > 95% and abolished the capacity of
      the phorbol ester to stimulate secretion during a subsequent dynamic perifusion.
      Culturing in TPA slightly improved the insulin secretory response to 15 mM
      glucose compared with control-cultured islets; however, sustained rates of 15 mM
      glucose-induced secretion from these islets were significantly less than the
      responses of freshly isolated islets. Islets cultured in TPA responded to 30 mM
      potassium with a markedly amplified insulin secretory response that was abolished
      by nitrendipine. Enhanced phosphorylation of several islet proteins was also
      observed in TPA-cultured islets compared with control-cultured islets. These
      findings demonstrate that culturing alone impairs glucose-induced secretion, a
      response that is improved but still subnormal compared with freshly isolated
      islet responses, if TPA is included in the culture medium. Sustained
      phosphorylation of several islet proteins in TPA-cultured islets may account, at
      least in part, for augmented calcium-dependent secretion.

PMID- 9612228
TI  - Differential regulation of single CFTR channels by PP2C, PP2A, and other
      phosphatases.
AB  - Cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel activity
      declines rapidly when excised from transfected Chinese hamster ovary (CHO) or
      human airway cells because of membrane-associated phosphatase activity. In the
      present study, we found that CFTR channels usually remained active in patches
      excised from baby hamster kidney (BHK) cells overexpressing CFTR. Those patches
      with stable channel activity were used to investigate the regulation of CFTR by
      exogenous protein phosphatases (PP). Adding PP2A, PP2C, or alkaline phosphatase
      to excised patches reduced CFTR channel activity by > 90% but did not abolish it
      completely. PP2B caused weak deactivation, whereas PP1 had no detectable effect
      on open probability (Po). Interestingly, the time course of deactivation by PP2C
      was identical to that of the spontaneous rundown observed in some patches after
      excision. PP2C and PP2A had distinct effects on channel gating Po declined during
      exposure to exogenous PP2C (and during spontaneous rundown, when it was observed)
      without any change in mean burst duration. By contrast, deactivation by exogenous
      PP2A was associated with a dramatic shortening of burst duration similar to that
      reported previously in patches from cardiac cells during deactivation of CFTR by
      endogenous phosphatases. Rundown of CFTR-mediated current across intact T84
      epithelial cell monolayers was insensitive to toxic levels of the PP2A inhibitor
      calyculin A. These results demonstrate that exogenous PP2C is a potent regulator
      of CFTR activity, that its effects on single-channel gating are distinct from
      those of PP2A but similar to those of endogenous phosphatases in CHO, BHK, and
      T84 epithelial cells, and that multiple protein phosphatases may be required for
      complete deactivation of CFTR channels.

PMID- 9612229
TI  - Alterations in AMP deaminase activity and kinetics in skeletal muscle of creatine
      kinase-deficient mice.
AB  - Alterations in the competency of the creatine kinase system elicit numerous
      structural and metabolic compensations, including changes in purine nucleotide
      metabolism. We evaluated molecular and kinetic changes in AMP deaminase from
      skeletal muscles of mice deficient in either cytosolic creatine kinase alone (M
      CK-/-) or also deficient in mitochondrial creatine kinase (CK-/-) compared with
      wild type. We found that predominantly fast-twitch muscle, but not slow-twitch
      muscle, from both M-CK-/- and CK-/- mice had much lower AMP deaminase; the
      quantity of AMP deaminase detected by Western blot was correspondingly lower,
      whereas AMP deaminase-1 (AMPD1) gene expression was unchanged. Kinetic analysis
      of AMP deaminase from mixed muscle revealed negative cooperativity that was
      significantly greater in creatine kinase deficiencies. Treatment of AMP deaminase
      with acid phosphatase abolished negative cooperative behavior, indicating that a
      phosphorylation-dephosphorylation cycle may be important in the regulation of AMP
      deaminase.

PMID- 9612230
TI  - Peroxynitrite inhibits amiloride-sensitive Na+ currents in Xenopus oocytes
      expressing alpha beta gamma-rENaC.
AB  - We examined the effect of peroxynitrite (ONOO-) on the cloned rat epithelial Na+
      channel (alpha beta gamma-rENaC) expressed in Xenopus oocytes. 3
      Morpholinosydnonimine (SIN-1) was used to concurrently generate nitric oxide
      (.NO) and superoxide (O2-.), which react to form ONOO-, a species known to
      promote protein nitration and oxidation. Under control conditions, oocytes
      displayed an amiloride-sensitive whole cell conductance of 7.4 +/- 2.8 (SE)
      microS. When incubated at 18 degrees C with SIN-1 (1 mM) for 2 h (final ONOO-
      concentration = 10 microM), the amiloride-sensitive conductance was reduced to
      0.8 +/- 0.5 microS. To evaluate whether the observed inhibition was due to ONOO-,
      as opposed to .NO, we also exposed oocytes to SIN-1 in the presence of urate (500
      microM), a scavenger of ONOO- and superoxide dismutase, which scavenges O2-.,
      converting SIN-1 from an ONOO- to an .NO donor. Under these conditions,
      conductance values remained at control levels following SIN-1 treatment.
      Tetranitromethane, an agent that oxidizes sulfhydryl groups at pH 6, also
      inhibited the amiloride-sensitive conductance. These data suggest that oxidation
      of critical sulfhydryl groups within rENaC by ONOO- directly inhibits channel
      activity.

PMID- 9612231
TI  - Equibiaxial strain and strain rate stimulate early activation of G proteins in
      cardiac fibroblasts.
AB  - Cardiac fibroblasts are responsible for the production of the extracellular
      matrix of the heart, with alterations of fibroblast function implicated in
      myocardial infarction and cardiac hypertrophy. Here the role of heterotrimeric
      GTP-binding proteins (G proteins) in the mechanotransduction of strain in rat
      cardiac fibroblasts was investigated. Cells in an equibiaxial stretch device were
      incubated with the photoreactive GTP analog azidoanalido [alpha-32P]GTP (AAGTP)
      and were subjected to various regimens of strain. Autoradiographic analysis
      showed a 42-kDa protein labeled for cells exposed to 12 cycles of 3% strain or 6
      cycles of 6% strain over 60 s (strain rate of 1.2%/s), whereas 6 cycles of 3%
      strain (0.6%/s) elicited no measurable response. To further investigate the role
      of strain rate, a single 6% cycle over 10 or 60 s (1.2% and 0.2%/s, respectively)
      was applied, with the more rapid cycle stimulating AAGTP binding, whereas the
      lower strain rate showed no response. In cells subjected to a single 6% cycle/10
      s, immunoprecipitation identified the AAGTP-labeled 42-kDa band as the G protein
      subunits G alpha q and G alpha i1. These results demonstrate that G protein
      activation represents one of the early mechanotransduction events in cardiac
      fibroblasts subjected to mechanical strain, with the rate at which the strain is
      applied modulating this response.

PMID- 9612232
TI  - Mechanism of hypoxia-stimulated glucose transport in rat skeletal muscle:
      potential role of glycogen.
AB  - We have previously reported that exercise training is associated with enhanced
      insulin-stimulated glucose transport activity and inhibited hypoxia-stimulated
      glucose transport activity in rat epitrochlearis muscle. Here we examine the
      potential role of muscle glycogen in the inhibited glucose transport response to
      hypoxia. Three days of swim training (2 x 3 h/day) produce a 100% increase in
      glycogen and a 70% increase in GLUT-4 in epitrochlearis muscle. Glucose transport
      after 1 h of hypoxia in muscles from fed exercise-trained (ET) rats is not
      significantly elevated above basal and is 40% lower than that in muscles from fed
      sedentary (SED) rats. Glycogen levels after 1 h of hypoxia are reduced by 27 and
      64% in muscles from fed ET and fed SED rats, respectively. After 2 h of hypoxia,
      glucose transport is significantly increased above basal in muscles from fed ET
      rats, but this response is still 55% lower than that in muscles from fed SED
      rats. After 2 h of hypoxia, glycogen is reduced by 50 and 83% in muscles from fed
      ET and fed SED rats, respectively. After a modified overnight fast (approximately
      4.5 g of chow), the glucose transport and glycogen responses to 1 h of hypoxia
      are not significantly different between muscles from ET and SED rats. These
      findings demonstrate a strong inverse relationship between glycogen and hypoxia
      stimulated glucose transport activity and that high levels of glycogen contribute
      to the inhibited glucose transport response to hypoxia. Furthermore, failure of
      the overexpression of GLUT-4 after exercise training to enhance the glucose
      transport response to contraction/hypoxia suggests selective targeting of the
      additional GLUT-4 to the insulin-responsive pool.

PMID- 9612233
TI  - Evidence against a role for the growth hormone-releasing peptide axis in human
      slow-wave sleep regulation.
AB  - A complex interrelationship exists between sleep and somatotropic activity. In
      humans, intravenous injections of growth hormone-releasing hormone (GHRH) given
      during sleep consistently stimulate slow-wave (SW) sleep, particularly when given
      in the latter part of the night. In the present study, the possible somnogenic
      effects induced under similar conditions by GH-releasing peptide (GHRP) were
      investigated in seven young healthy men. Bolus intravenous injections of GHRP-2
      (1 microgram/kg body wt) or saline, in randomized order, were given after 60 s of
      the third rapid-eye-movement period. All GHRP injections were immediately
      followed by transient prolactin elevations and by GH pulses of a magnitude within
      or around the upper limit of the physiological range. Except for a nonsignificant
      tendency to increased amounts of wakefulness during the 1st h after the
      injection, no effects of GHRP-2 administration on sleep were detected. There was
      in particular no enhancement of SW sleep. Thus, in contrast to GHRH, late-night
      single injections of GHRP-2 at a dosage resulting in similar GH elevations have
      no stimulatory effects on SW sleep. The present data provide evidence against the
      involvement of the GHRP axis in human SW sleep regulation.

PMID- 9612234
TI  - Training-induced alterations in fat and carbohydrate metabolism during exercise
      in elderly subjects.
AB  - Compared with young adults, fat oxidation is lower in elderly persons during
      endurance exercise performed at either the same absolute or relative intensity.
      We evaluated the effect of 16 wk of endurance training on fat and glucose
      metabolism during 60 min of moderate intensity exercise [50% of pretraining peak
      oxygen consumption (VO2peak)] in six elderly men and women (74 +/- 2 yr).
      Training caused a 21% increase in mean VO2peak. The average rate of fat oxidation
      during exercise was greater after (221 +/- 28 mumol/min) than before (166 +/- 17
      mumol/min) training (P = 0.002), and the average rate of carbohydrate oxidation
      during exercise was lower after (3,180 +/- 461 mumol/min) than before (3,937 +/-
      483 mumol/min) training (P = 0.003). Training did not cause a significant change
      in glycerol rate of appearance (Ra), free fatty acid (FFA) Ra, and FFA rate of
      disappearance during exercise. However, glucose Ra during exercise was lower
      after (1,027 +/- 95 mumol/min) than before (1,157 +/- 69 mumol/min) training (P =
      0.01). These results demonstrate that a 16-wk period of endurance training
      increases fat oxidation without a significant change in lipolysis (glycerol Ra)
      or FFA availability (FFA Ra) during exercise in elderly subjects. Therefore, the
      training-induced increase in fat oxidation during exercise is likely related to
      alterations in skeletal muscle fatty acid metabolism.

PMID- 9612235
TI  - Effect of pregnancy on the metabolic clearance rate and the volume of
      distribution of oxytocin in the baboon.
AB  - Pharmacokinetic parameters of oxytocin (OT) metabolism were determined during the
      last third of pregnancy and again 4-8 wk after delivery in the baboon. Animals
      were placed on a tether system with venous and arterial access and a continuous
      monitoring of uterine contractions during gestation. Two methods of determining
      OT pharmacokinetics were utilized (bolus injection vs. continuous infusion). The
      metabolic clearance rate of OT as determined during the bolus trials (n = 7) was
      22.2 +/- 1.5 ml.min-1.kg-1 in pregnancy and 16.3 +/- 1.4 ml.min-1.kg-1 postpartum
      (P < 0.05), respectively, and 23.7 +/- 2.8 vs. 16.9 +/- 3.7 ml.min-1.kg-1 (P <
      0.05), respectively, as determined during the 1-h infusion trials (n = 4). The
      initial dilution volume and the volume of distribution at steady state of OT
      after administration did not differ between pregnant and postpartum animals (P >
      0.05). The mean residence time (MRT) of OT was shorter during pregnancy, 7.7 +/-
      0.8 vs. 10.8 +/- 1.2 min postpartum (P < 0.05). In summary, OT metabolism during
      pregnancy in the baboon is characterized by 1) increased clearance rate (1.4
      fold), 2) accelerated turnover due to the shorter MRT, and 3) unaltered
      distribution.

PMID- 9612236
TI  - Glucose-induced pulsatile insulin release from single islets at stable and
      oscillatory cytoplasmic Ca2+.
AB  - The cytoplasmic Ca2+ concentration ([Ca2+]i) and insulin release were measured
      simultaneously in mouse pancreatic islets cultured overnight. [Ca2+]i was 105 nM
      and insulin release 3 pmol.g-1.s-1 at 3 mM glucose. An increase to 7 mM glucose
      reduced [Ca2+]i transiently, whereas insulin release doubled and was pulsatile
      with a frequency of 0.47 min-1. [Ca2+]i oscillations with similar frequency
      appeared at 11 mM glucose associated with increased amplitude of the insulin
      oscillations, raising the secretory rate 10-fold. In the presence of 16 and 20 mM
      glucose [Ca2+]i was > 300 nM and showed no oscillations apart from two islets,
      which demonstrated [Ca2+]i oscillations with small amplitude at 16 mM glucose.
      Insulin release with maintained frequency increased by 46 and 31%, respectively.
      When the glucose concentration was increased from 3 to 11 mM, [Ca2+]i decreased
      with a nadir that appeared significantly earlier than when the glucose
      concentration was raised from 3 to 7 mM. Glucose-induced insulin release from the
      isolated islet is pulsatile both at stable and oscillatory [Ca2+]i, with changes
      in secretory rate caused by the sugar also when [Ca2+]i is unchanged.

PMID- 9612237
TI  - Phenylbutyrate-induced glutamine depletion in humans: effect on leucine
      metabolism.
AB  - The present study was designed to determine whether sodium phenylbutyrate (phi B)
      acutely induces a decrease in plasma glutamine in healthy humans, and, if so,
      will decrease estimates of whole body protein synthesis. In a first group of
      three healthy subjects, graded doses (0, 0.18, and 0.36 g.kg-1.day-1) of phi B
      were administered for 24 h before study: postabsorptive plasma glutamine
      concentration declined in a dose-dependent manner, achieving an approximately 25%
      decline for a dose of 0.36 g phi B.kg-1.day-1. A second group of six healthy
      adults received 5-h infusions of L-[1-14C]leucine and L-[1-13C]glutamine in the
      postabsorptive state on two separate days: 1) under baseline conditions and 2)
      after 24 h of oral treatment with phi B (0.36 g.kg-1.day-1) in a randomized
      order. The 24-h phenylbutyrate treatment was associated with 1) an approximately
      26% decline in plasma glutamine concentration from 514 +/- 24 to 380 +/- 15
      microM (means +/- SE; P < 0.01 with paired t-test) with no change in glutamine
      appearance rate or de novo synthesis; 2) no change in leucine appearance rate
      (Ra), an index of protein breakdown (123 +/- 7 vs. 117 +/- 5 mumol.kg-1.h-1; not
      significant); 3) an approximately 22% rise in leucine oxidation (Ox) from 23 +/-
      2 to 28 +/- 2 mumol.kg-1.h-1 (P < 0.01), resulting in an approximately 11%
      decline in nonoxidative leucine disposal (NOLD = Ra-Ox), an index of protein
      synthesis, from 100 +/- 6 to 89 +/- 5 mumol.kg-1.h-1 (P < 0.05). The data suggest
      that, in healthy adults, 1) large doses of oral phenylbutyrate can be used as a
      "glutamine trap" to create a model of glutamine depletion; 2) a moderate decline
      in plasma glutamine does not enhance rates of endogenous glutamine production;
      and 3) a short-term depletion of plasma glutamine decrease estimates of whole
      body protein synthesis.

PMID- 9612238
TI  - Dual-energy X-ray absorptiometry: fat estimation errors due to variation in soft
      tissue hydration.
AB  - Dual-energy X-ray absorptiometry (DXA) is rapidly gaining acceptance as a
      reference method for analyzing body composition. An important and unresolved
      concern is whether and to what extent variation in soft tissue hydration causes
      errors in DXA fat estimates. The present study aim was to develop and validate a
      DXA physical hydration model and then to apply this model by simulating errors
      arising from hypothetical overhydration states. The DXA physical hydration model
      was developed by first linking biological substance elemental content with photon
      attenuation. The validated physical model was next extended to describe photon
      attenuation changes anticipated when predefined amounts of two known composition
      components are mixed, as would occur when overhydration develops. Two
      overhydration models were developed in the last phase of study, formulated on
      validated physical models, and error was simulated for fluid surfeit states.
      Results indicate that systematic errors in DXA percent fat arise with added
      fluids when fractional masses are varied as a percentage of combined fluid + soft
      tissue mass. Three independent determinants of error magnitude were established:
      elemental content of overhydration fluid, fraction of combined fluid + soft
      tissue as overhydration fluid, and initial soft tissue composition. Small but
      systematic and predictable errors in DXA soft tissue composition analysis thus
      can arise with fluid balance changes.

PMID- 9612239
TI  - Human kidney and liver gluconeogenesis: evidence for organ substrate selectivity.
AB  - To assess the contribution of the human kidney to gluconeogenesis (GN) and its
      role in conversion of glutamine and alanine to glucose, we used a combination of
      isotopic and organ balance techniques in nine normal postabsorptive volunteers
      and measured both overall and renal incorporation of these precursors into
      glucose before and after infusion of epinephrine. In the postabsorptive basal
      state, renal incorporation of glutamine (27 +/- 2 mumol/min) and alanine (2.1 +/-
      0.5 mumol/min) into glucose accounted for 72.8 +/- 3.3 and 3.9 +/- 0.5% of their
      overall incorporation into glucose (37 +/- 2 and 51 +/- 6 mumol/min,
      respectively) and 19.0 +/- 3.5 and 1.4 +/- 0.2%, respectively, of overall renal
      glucose release. Infusion of epinephrine, which increased systemic and renal
      glucose release more than twofold (P < 0.001), increased overall glutamine and
      alanine incorporation into glucose (both P < 0.001) and increased renal GN from
      glutamine (P < 0.001) but not from alanine (P = 0.15). Renal glutamine GN now
      accounted for 90.3 +/- 4.0% of overall glutamine GN (P = 0.01 vs. basal), whereas
      renal alanine GN still accounted for only 4.8 +/- 1.7% of overall alanine GN (P =
      0.36 vs. basal). With the assumption that kidney and liver are the only
      gluconeogenic organs in humans, these results indicate that glutamine GN occurs
      primarily in kidney, whereas alanine GN occurs almost exclusively in liver.
      Isotopic studies of glutamine and alanine incorporation into plasma glucose may
      provide a selective, noninvasive method to assess hepatic and renal GN.

PMID- 9612240
TI  - Dissociation of the effects of amylin on osteoblast proliferation and bone
      resorption.
AB  - This study assesses the structure-activity relationships of the actions of amylin
      on bone. In fetal rat osteoblasts, only intact amylin and amylin-(1-8) stimulated
      cell proliferation (half-maximal concentrations 2.0 x 10(-11) and 2.4 x 10(-10)
      M, respectively). Amylin-(8-37), COOH terminally deamidated amylin, reduced
      amylin, and reduced amylin-(1-8) (reduction results in cleavage of the disulfide
      bond) were without agonist effect but acted as antagonists to the effects of both
      amylin and amylin-(1-8). Calcitonin gene-related peptide-(8-37) also antagonized
      the effects of amylin and amylin-(1-8) on osteoblasts but was substantially less
      potent in this regard than amylin-(8-37). In contrast, inhibition of bone
      resorption in neonatal mouse calvariae only occurred with the intact amylin
      molecule and was not antagonized by any of these peptides. The rate of catabolism
      of the peptides in calvarial cultures was not accelerated in comparison with that
      of intact amylin. This dissociation of the actions of amylin suggests that it
      acts through two separate receptors, one on the osteoclast (possibly the
      calcitonin receptor) and a second on the osteoblast.

PMID- 9612241
TI  - PACAP stimulates insulin secretion but inhibits insulin sensitivity in mice.
AB  - Although pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates
      insulin secretion, its net influence on glucose homeostasis in vivo has not been
      established. We therefore examined the action of PACAP-27 and PACAP-38 on insulin
      secretion, insulin sensitivity, and glucose disposal as derived from the minimal
      model of glucose disappearance during an intravenous glucose tolerance test in
      anesthetized mice. PACAP-27 and PACAP-38 markedly and equipotently potentiated
      glucose-stimulated insulin secretion, with a half-maximal effect at 33 pmol/kg.
      After PACAP-27 or PACAP-38 (1.3 nmol/kg), the acute (1-5 min) insulin response
      was 3.8 +/- 0.4 nmol/l (PACAP-27) and 3.3 +/- 0.3 nmol/l (PACAP-38),
      respectively, vs. 1.4 +/- 0.1 nmol/l after glucose alone (P < 0.001), and the
      total area under the curve for insulin (AUCinsulin) was potentiated by 60% (P <
      0.001). In contrast, PACAP-27 and PACAP-38 reduced the insulin sensitivity index
      (SI) [0.23 +/- 0.04 10(-4) min-1/(pmol/l) for PACAP-27 and 0.29 +/- 0.06 10(-4)
      min-1/(pmol/l) for PACAP-38 vs. 0.46 +/- 0.02 10(-4) min-1/(pmol/l) for controls
      (P < 0.01)]. Furthermore, PACAP-27 or PACAP-38 did not affect glucose elimination
      determined as glucose half-time or the glucose elimination rate after glucose
      injection or the area under the curve for glucose. Moreover, glucose
      effectiveness and the global disposition index (AUCinsulin times SI) were not
      affected by PACAP-27 or PACAP-38. Finally, when given together with glucose,
      PACAP-27 did not alter plasma glucagon or norepinephrine levels but significantly
      increased plasma epinephrine levels. We conclude that PACAP, besides its marked
      stimulation of insulin secretion, also inhibits insulin sensitivity in mice, the
      latter possibly explained by increased epinephrine. This complex action explains
      why the peptide does not enhance glucose disposal.

PMID- 9612242
TI  - Mass isotopomer study of the nonoxidative pathways of the pentose cycle with [1,2
      13C2]glucose.
AB  - We present a single-tracer method for the study of the pentose phosphate pathway
      (PPP) using [1,2-13C2]glucose and mass isotopomer analysis. The metabolism of
      [1,2-13C2]glucose by the glucose-6-phosphate dehydrogenase, transketolase (TK),
      and transaldolase (TA) reactions results in unique pentose and lactate
      isotopomers with either one or two 13C substitutions. The distribution of these
      isotopomers was used to estimate parameters of the PPP using the model of Katz
      and Rognstad (J. Katz and R. Rognstad. Biochemistry 6: 2227-2247, 1967). Mass and
      position isotopomers of ribose, and lactate and palmitate (products from triose
      phosphate) from human hepatoma cells (Hep G2) incubated with 30% enriched [1,2
      13C2]glucose were determined using gas chromatography-mass spectrometry. After 24
      72 h incubation, 1.9% of lactate molecules in the medium contained one 13C
      substitution (m1) and 10% contained two 13C substitutions (m2). A similar m1-to
      m2 ratio was found in palmitate as expected. Pentose cycle (PC) activity
      determined from incubation with [1,2-13C2]glucose was 5.73 +/- 0.52% of the
      glucose flux, which was identical to the value of PC (5.55 +/- 0.73%) determined
      by separate incubations with [1-13C] and [6-13C]glucose, 13C was found to be
      distributed in four ribose isotopomers ([1-13C]-, [5-13C]-, [1,2-13C2]-, and [4,5
      13C2]ribose). The observed ribose isotopomer distribution was best matched with
      that provided from simulation by substituting 0.032 for TK and 0.85 for TA
      activity relative to glucose uptake into the model of Katz and Rognstad. The use
      of [1,2-13C2]glucose not only permits the determination of PC but also allows
      estimation of relative rates through the TK and TA reactions.

PMID- 9612243
TI  - Effects of thiopental anesthesia on local rates of cerebral protein synthesis in
      rats.
AB  - We have examined the effects of a surgical level of thiopental anesthesia in
      adult male rats on local rates of cerebral protein synthesis with the
      quantitative autoradiographic L-[1-14C]leucine method. The relative contribution
      of leucine derived from protein breakdown to the intracellular precursor amino
      acid pool for protein synthesis was found to be statistically significantly
      decreased in the anesthetized rats compared with controls. In the brain as a
      whole and in 30 of the 35 brain regions examined, rates of protein synthesis were
      decreased (1-11%) in the anesthetized rats. Decreases were statistically
      significant (P < or = 0.05) in the brain as a whole and in six of the regions,
      and they approached statistical significance in an additional 13 regions,
      indicating a tendency for a generalized but small effect.

PMID- 9612244
TI  - Total body lipid and triglyceride response to energy deficit: relevance to body
      composition models.
AB  - Although the study of human body composition is advancing rapidly, confusion
      still prevails regarding the molecular-level lipid component. Most molecular
      level body composition models are presently based on the overall hypothesis that
      nontriglyceride lipids constitute an insignificant proportion of total body
      lipid. A single lipid or "fat" component consisting of triglycerides is thus
      assumed in most molecular-level body composition models. To test this hypothesis,
      the present study, carried out in adult rats, was designed to examine two
      questions: 1) What is the proportion of total lipids as triglycerides? and 2) Is
      this proportion constant or does it change with negative energy balance and
      weight loss produced by calorie restriction and increased exercise? Results
      indicated that with negative energy balance and weight loss there were
      progressive losses of total body triglyceride and lipid. The proportion of total
      lipids as triglyceride was 0.83 +/- 0.08 (SD) in control animals, with reductions
      at 2 and 9 wk of energy restriction [0.82 +/- 0.04 (P = NS vs. control) and 0.70
      +/- 0.15 (P = 0.05)] and at 9 wk for energy restriction plus exercise [0.67 +/-
      0.09 (P = 0.003)]. Nontriglyceride lipids comprised 2.8% of carcass weight at
      baseline and decreased to 2.2% by 9 wk of energy restriction and exercise (P =
      NS). Substantial differences were observed between body composition ratios
      expressed as percentages of the lipid-free body mass (LFM) and triglyceride-free
      body mass (TGFM); (e.g., total body water/LFM and TGFM in controls = 72.7 +/- 0.7
      and 70.4 +/- 2.2, respectively; P = 0.02). These observations strongly support
      the existence and importance of nontriglyceride lipids as a body composition
      component that responds independently from storage triglycerides, with negative
      energy balance produced by food restriction and exercise.

PMID- 9612246
TI  - Glutamate transport asymmetry in renal glutamine metabolism.
AB  - D-Glutamate (Glu) was previously shown to block L-Glu uptake and accelerate
      glutaminase flux in cultured kidney cells [Welbourne, T. C., and D. Chevalier.
      Am. J. Physiol. 272 (Endocrinol. Metab. 35): E367-E370, 1997]. To test whether D
      Glu would be taken up by the intact functioning kidney and effect the same
      response in vivo, male Sprague-Dawley rats were infused with D-Glu (2.6
      mumol/min), and renal uptake of D- and L-Glu was determined from chemical and
      radiolabeled arteriovenous Glu concentration differences times renal plasma flow.
      The amount removed was then compared with that amount filtered to obtain the
      antiluminal contribution. In the controls, L-Glu uptake measured as net removal
      was 33% of the arterial L-Glu load and not different from that filtered, 27%;
      however, the unidirectional uptake was actually 58% of the arterial load,
      indicating that antiluminal uptake contributes at least half to the overall Glu
      consumption. Surprisingly, the kidneys showed a more avid removal of D-Glu,
      removing 73% of the arterial load, indicating uptake predominantly across the
      antiluminal cell surface. Furthermore, uptake of D-Glu was associated with a 55%
      reduction in L-Glu uptake, with the residual amount taken up equivalent to that
      filtered; D-Glu did not increase the excretion of the L-isomer. However,
      elevating plasma L-Glu concentration reduced uptake of the D-isomer, suggesting a
      shared antiluminal transporter. Thus there is an apparent asymmetrical
      distribution of the D-Glu transporter. Under these conditions, kidney cortex L
      Glu content decreased 44%, whereas net glutamine (Gln) uptake increased sevenfold
      (170 +/- 89 to 1,311 +/- 219 nmol/min, P < 0.01) and unidirectional uptake nearly
      threefold (393 +/- 121 to 1,168 +/- 161 nmol/min, P < 0.05); this large Gln
      consumption was paralleled by an increase in ammonium production so that the
      ratio of production to consumption approaches 2, consistent with accelerated Gln
      deamidation and subsequent Glu deamination. These results point to a functional
      asymmetry (antiluminal vs. luminal) for Glu transporter activity, which
      potentially plays an important role in modulating Gln metabolism and renal
      function.

PMID- 9612247
TI  - Insulin inhibits vascular smooth muscle contraction at a site distal to
      intracellular Ca2+ concentration.
AB  - Several hypertensive states are associated with resistance to insulin-induced
      glucose disposal and insulin-induced vasodilation. Insulin can inhibit vascular
      smooth muscle (VSM) contraction at the level of the VSM cell, and resistance to
      insulin's inhibition of VSM cell contraction may be of pathophysiological
      importance. To understand the VSM cellular mechanisms by which insulin resistance
      leads to increased VSM contraction, we sought to determine how insulin inhibits
      contraction of normal VSM. It has been shown that insulin lowers the contractile
      agonist-stimulated intracellular Ca2+ (Ca2+i) transient in VSM cells. In this
      study, our goal was to see whether insulin inhibits VSM cell contraction at steps
      distal to Ca2+i and, if so, to determine whether the mechanism is dependent on
      nitric oxide synthase (NOS) and cGMP. Primary cultured VSM cells from canine
      femoral artery were bathed in a physiological concentration of extracellular Ca2+
      and permeabilized to Ca2+ with a Ca2+ ionophore, either ionomycin or A-23187. The
      resultant increase in Ca2+i contracted individual cells, as measured by
      photomicroscopy. Preincubating cells with 1 nM insulin for 30 min did not affect
      basal Ca2+i or the ionomycin-induced increase in Ca2+i, as determined by fura 2
      fluorescence measurements, but it did inhibit ionomycin- and A-23187-induced
      contractions by 47 and 51%, respectively (both P < 0.05). In the presence of 1.0
      microM ionized Ca2+, ionomycin-induced contractions were inhibited by insulin in
      a dose-dependent manner. In the presence of ionomycin, insulin increased cGMP
      production by 43% (P < 0.05). 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10
      microM), a selective inhibitor of guanylate cyclase that blocked cGMP production
      in these cells, completely blocked the inhibition by insulin of ionomycin-induced
      contraction. It was found that the cells expressed the inducible isoform of NOS.
      NG-monomethyl-L-arginine or NG-nitro-L-arginine methyl ester (0.1 mM), inhibitors
      of NOS, did not affect ionomycin-induced contraction but prevented insulin from
      inhibiting contraction. We conclude that insulin stimulates cGMP production and
      inhibits VSM contraction in the presence of elevated Ca2+i. This inhibition by
      insulin of VSM contraction at sites where Ca2+i could not be rate limiting is
      dependent on NOS and cGMP.

PMID- 9612245
TI  - Mechanisms contributing to angiotensin II regulation of body weight.
AB  - Previous studies in our laboratory have implicated adipose tissue as a potential
      site for local angiotensin II (ANG II) synthesis. However, functions of ANG II in
      adipose tissue and the impact of ANG II on body weight regulation are not well
      defined. To study the effect of ANG II on body weight, a chronic ANG II infusion
      model was used. In study 1, a low dose of ANG II (175 ng.kg-1.min-1) was infused
      into rats for 14 days. Plasma ANG II levels were not elevated after 14 days of
      infusion. ANG II-infused rats did not gain weight over the 14-day protocol and
      exhibited a lower body weight than controls on day 8. Food intake was not
      altered, but water intake was increased in ANG II-infused rats. Blood pressure
      gradually increased to significantly elevated levels by day 14. Thermal infrared
      imaging demonstrated an increase in abdominal surface temperature. Measurement of
      organ mass demonstrated site-specific reductions in white adipose tissue mass
      after ANG II infusion. In study 2, the dose-response relationship for ANG II
      infusion (200, 350, and 500 ng.kg-1.min-1) was determined. Body weight
      (decrease), blood pressure (increase), white adipose mass (decrease), plasma ANG
      II levels (increase), and plasma leptin levels (decrease) were altered in a dose
      related manner after ANG II infusion. In study 3, the effect of ANG II infusion
      (350 ng.kg-1.min-1) was examined in rats treated with the vasodilator
      hydralazine. Hydralazine treatment normalized blood pressure in ANG II-infused
      rats. The effect of ANG II to decrease body weight was augmented in hydralazine
      treated rats. These results demonstrate that low levels of ANG II infusion
      regulate body weight through mechanisms related to increased peripheral
      metabolism and independent of elevations in blood pressure.

PMID- 9612249
TI  - Distribution and kinetics of amylin in humans.
AB  - The aim of the study was to determine the apparent volume of distribution (VTOT),
      total body clearance (CL), fractional clearance, and mean residence time (MRT) of
      the beta-cell hormone amylin. We therefore performed an intravenous injection of
      50 micrograms of human synthetic amylin (amlintide) in nine healthy male subjects
      during suppression of endogenous amylin release by intravenous somatostatin (0.06
      microgram.kg-1.min-1). The plasma levels of amylin concentrations over time were
      analyzed using three-exponential curves. VTOT was 173 +/- 16 ml/kg and was not
      different from that of insulin reported in the literature (157 ml/kg). MRT was
      27.7 +/- 2.1 min and thus two times the reported value for insulin (14.1 min) and
      C-peptide (16.4 min). CL and fractional CL were 6.2 +/- 0.2 ml.kg-1.min-1 and
      0.038 +/- 0.003 min-1, respectively. Fractional CL is therefore definitely lower
      than that reported for insulin (0.12-0.2 min-1) but is, however, in the range of
      that of C-peptide (0.05 min-1). In conclusion, clearance of amylin is similar to
      that reported for C-peptide and much slower than insulin, indicating that the
      commonly used molar insulin-to-amylin ratio does not reflect the correct
      relationship of the two peptides.

PMID- 9612248
TI  - Hepatic glucose disposition during concomitant portal glucose and amino acid
      infusions in the dog.
AB  - The effect of concomitant intraportal infusion of glucose and gluconeogenic amino
      acids (AA) on net hepatic glucose uptake (NHGU) and glycogen synthesis was
      examined in 42-h-fasted dogs. After a basal period, there was a 240-min
      experimental period during which somatostatin was infused continuously into a
      peripheral vein and insulin and glucagon (at 3-fold basal and basal rates,
      respectively) and glucose (18.3 mumol.kg-1.min-1) were infused intraportally. One
      group (PoAA, n = 7) received an AA mixture intraportally at 7.6 mumol.kg-1.min-1,
      whereas the other group (NoAA, n = 6) did not receive AA. Arterial blood glucose
      concentrations and hepatic glucose loads were the same in the two groups. NHGU
      averaged 4.8 +/- 2.0 (PoAA) and 9.4 +/- 2.0 (NoAA) mumol.kg-1.min-1 (P < 0.05),
      and tracer-determined hepatic glucose uptake was 4.6 +/- 1.6 (PoAA) and 10.0 +/-
      1.7 (NoAA) mumol.kg-1.min-1 (P < 0.05). AA data for PoAA and NoAA, respectively,
      were as follows: arterial blood concentrations, 1,578 +/- 133 vs. 1,147 +/- 86
      microM (P < 0.01); hepatic loads, 56 +/- 3 vs. 32 +/- 4 mumol.kg-1.min-1 (P <
      0.01); and net hepatic uptakes, 14.1 +/- 1.4 vs. 5.6 +/- 0.4 mumol.kg-1.min-1 (P
      < 0.01). The rate of net hepatic glycogen synthesis was 7.5 +/- 1.9 (PoAA) vs.
      10.7 +/- 2.3 (NoAA) mumol.kg-1.min-1 (P = 0.1). In a net sense, intraportal
      gluconeogenic amino acid delivery directed glucose carbon away from the liver.
      Despite this, net hepatic carbon uptake was equivalent in the presence and
      absence of amino acid infusion.

PMID- 9612250
TI  - Genetic and environmental influences on prolactin secretion during wake and
      during sleep.
AB  - To delineate the contributions of genetic and environmental factors in the
      regulation of human prolactin (PRL) secretion, the 24-h profile of plasma PRL was
      obtained at 15-min intervals in 10 pairs of monozygotic and 10 pairs of dizygotic
      twins. Sleep was monitored polygraphically. PRL secretory rates were derived from
      plasma concentrations by deconvolution. Diurnal (24-h) variations were quantified
      by a regression curve to define nadir, acrophase, and amplitude. Pulses of PRL
      secretion were identified using a computerized algorithm. A procedure
      specifically developed for twin studies was used to partition the variance into
      genetic and environmental contributions. Significant genetic effects were
      identified for daytime PRL concentrations, rhythm amplitude, and overall wave
      shape of the daily PRL profile. In contrast, environmental effects were dominant
      for mean concentrations during sleep, total secretory output during sleep,
      overall 24-h concentrations, and total 24-h secretion. However, when
      interindividual variations in sleep fragmentation were taken into account, the
      estimates of genetic variance for PRL concentrations and secretion during sleep
      approached statistical significance. Significant genetic influences were
      identified for slow-wave sleep (SWS). Because SWS is associated with increased
      nocturnal PRL secretion, it is possible that genetic effects on PRL secretion
      during sleep reflect genetic influences on SWS. In conclusion, genetic factors
      determine partially both the basal daytime concentrations of PRL and the temporal
      organization of PRL secretion over the 24-h cycle in normal young men.

PMID- 9612251
TI  - Intracellular Mg2+ regulates ADP phosphorylation and adenine nucleotide synthesis
      in human erythrocytes.
AB  - 13C- and 31P-NMR were used in methylene blue-treated human erythrocytes to
      determine the dependence on intracellular Mg2+ concentration ([Mg2+]i) of the
      pentose phosphate pathway (PPP), the glycolytic pathway, and adenine nucleotide
      synthesis. The PPP flux had an [Mg2+]i at half-maximal velocity ([Mg2+]i,0.5) of
      0.02 mM, well below the physiological range (0.2-0.7 mM). Flux through the PPP
      was reduced at higher [Mg2+]i as flux through phosphofructokinase was increased
      ([Mg2+]i,0.5 = 0.16 mM). [Mg2+]i,0.5 of phosphoglycerate kinase flux, which
      equals net ADP phosphorylation rate, was 0.27 mM, well within the physiological
      [Mg2+]i range. The rate of adenine nucleotide synthesis from [2-13C]glucose
      derived ribose 5-phosphate and exogenous adenine also exhibited dependence on
      [Mg2+]i but was not saturable up to 1.6 mM. Therefore, net flux through the PPP
      and glycolytic pathways in erythrocytes is not strongly dependent on [Mg2+]i at
      physiological ion concentrations, but both ADP phosphorylation and adenine
      nucleotide synthesis are likely to be regulated by normal fluctuations in
      [Mg2+]i.

PMID- 9612252
TI  - Lymphocyte transfer in streptozotocin-induced diabetes: adhesion of donor cells
      to islet endothelium.
AB  - The interaction between intravenously transferred lymphocytes derived from
      spleens of multiple low-dose streptozotocin-diabetic mice with islet, exocrine
      pancreatic, and gastric mucosal endothelium of nondiabetic recipient mice was
      investigated by in vivo microscopy. Donor lymphocytes were stained with acridine
      red in vitro. The adoptive transfer of these cells from diabetic donor animals
      resulted in significantly increased lymphocyte rolling (4.46 +/- 1.32%, P < 0.05)
      and adhesion (3.86 +/- 1.04%, P < 0.05) in islets of nondiabetic recipients that
      had been pretreated with a single subdiabetogenic dose of streptozotocin. No
      increased endothelial interaction was noted in nonpretreated recipients or in
      experiments with nondiabetic donors. Rolling (1.19 +/- 0.61 to 2.71 +/- 0.62%)
      and adhesion (0.61 +/- 0.33 to 2.80 +/- 0.97%) of donor lymphocytes were low in
      exocrine pancreatic and gastric mucosal control tissue. It is concluded that, in
      this animal model, lymphocytes from diabetic donors interact preferentially with
      recipient islet endothelium. However, additional stimulation of recipient islet
      endothelium by exogenous factors is necessary to enable transferred cells to
      adhere to pancreatic islets.

PMID- 9612253
TI  - Metabolite levels in human skeletal muscle and adipose tissue studied with
      microdialysis at low perfusion flow.
AB  - To identify a perfusion flow at which the interstitial fluid completely
      equilibrates with the microdialysis perfusion fluid, a protocol with successively
      lower perfusion flows was used. A colloid was included in the perfusion fluid to
      make sampling possible at the lowest perfusion flows. At 0.16 microliter/min, the
      measured metabolites had reached a complete equilibration in both tissues, and
      the measured concentrations of glucose, glycerol, and urea were in good agreement
      with expected tissue-specific levels. The glucose concentration in adipose tissue
      (4.98 +/- 0.14 mM) was equal to that of plasma (5.07 +/- 0.07 mM), whereas the
      concentration in muscle (4.41 +/- 0.11 mM) was lower than in plasma and adipose
      tissue (P < 0.001). The concentration of lactate was higher (P < 0.001) in muscle
      (2.39 +/- 0.22 mM) than in adipose tissue (1.30 +/- 0.12 mM), whereas the
      glycerol concentration in adipose tissue (233 +/- 19.7 microM) was higher (P <
      0.001) than in muscle (40.8 +/- 3.0 microM) and in plasma (68.7 +/- 3.97 microM).
      The concentration of urea was equal in the two tissues. Overall, the study
      indicates that microdialysis at a low perfusion flow may be a tool to
      continuously monitor tissue interstitial concentrations.

PMID- 9612254
TI  - Effects of hyperthyroidism on vascular contractile and relaxation responses.
AB  - Previous research has shown that skeletal muscle blood flow, at rest and during
      muscular contractions, is elevated in the hyperthyroid state. We hypothesized
      that reduced vascular contractile and enhanced endothelium-dependent relaxation
      responses contribute to these observations. To test these hypotheses, male rats
      were administered triiodothyronine (Hyper, n = 27; 300 micrograms/kg) for 6-12
      wk. Compared with euthyroid control rats (Eut, n = 27), Hyper exhibited left
      ventricular hypertrophy (Eut, 2.01 +/- 0.04 mg/g body wt; Hyper, 2.70 +/- 0.06; P
      < 0.0005) and greater oxidative enzyme activity in several skeletal muscles (all
      P < 0.0005). Vascular rings, 2-3 mm in axial length, were prepared from abdominal
      aortas, and responses to vasoactive agents were determined in vitro. Compared
      with Eut, vascular rings with intact endothelium from Hyper exhibited reductions
      in contractile responses to norepinephrine (NE) across a range of NE
      concentrations (P < 0.05). Maximal tension developed in response to NE was
      reduced approximately 30% in hyperthyroidism (Eut, 3.8 +/- 0.2 g; Hyper, 2.6 +/-
      0.4; P < 0.01). Contractile responses to NE were not different between Eut and
      Hyper in rings denuded of endothelium. Maximal vasorelaxation responses to
      acetylcholine (ACh), after precontraction with NE (10(-7) M), were enhanced in
      the hyperthyroid state (Eut, 65.1 +/- 4.8%; Hyper, 84.0 +/- 7.1; P < 0.05).
      Enhanced vasorelaxation to ACh was also observed when precontraction was induced
      by prostaglandin F2 alpha. These findings indicate that vascular contractile and
      relaxation responses are altered in male hyperthyroid rats.

PMID- 9612255
TI  - Limitations in estimating gluconeogenesis and Cori cycling from mass isotopomer
      distributions using [U-13C6]glucose.
AB  - Tayek and Katz proposed calculating gluconeogenesis's contributions to glucose
      production and Cori cycling from mass isotopomer distributions in blood glucose
      and lactate during [U-13C6]glucose infusion [Tayek, J. A., and J. Katz. Am. J.
      Physiol. 272 (Endocrinol. Metab. 35): E476-E484, 1997]. However, isotopic
      exchange was not adequately differentiated from dilution, nor was condensation of
      labeled with unlabeled triose phosphates properly equated. We introduce and apply
      corrected equations to data from subjects fasted for 12 and 60 h. Impossibly low
      contributions of gluconeogenesis to glucose production at 60 h are obtained (23
      41%). Distributions in overnight-fasted normal subjects calculate to only
      approximately 18%. Cori cycling estimates are approximately 10-15% after
      overnight fasting and 20% after 60 h of fasting. There are several possible
      reasons for the underestimates. The contribution of gluconeogenesis is
      underestimated because glucose production from glycerol and amino acids not
      metabolized via pyruvate is ascribed to glycogenolysis. Labeled oxaloacetate and
      alpha-ketoglutarate can exchange during equilibrium with circulating unlabeled
      aspartate, glutamate, and glutamine. Also, the assumption that isotopomer
      distributions in arterial lactate and hepatic pyruvate are the same may not be
      fulfilled.

PMID- 9612256
TI  - Current concepts in mucosal immunity. V Role of M cells in transepithelial
      transport of antigens and pathogens to the mucosal immune system.
AB  - Specialized epithelial M cells, a phenotype that occurs only in the epithelium
      over organized lymphoid follicles, deliver samples of foreign material by
      transepithelial transport from the lumen to organized lymphoid tissues within the
      mucosa of the small and large intestines. Mounting evidence indicates that a
      complex interplay of mucosal lymphoid cells and luminal microorganisms with
      epithelial cells underlies differentiation of the M cell phenotype. The cellular
      and molecular features of M cells that promote adherence and transport of
      antigens and microorganisms are crucial for the design of mucosal vaccines and
      for understanding the strategies that pathogens use to exploit this pathway.

PMID- 9612257
TI  - G protein-coupled receptors in gastrointestinal physiology. II. Regulation of
      neuropeptide receptors in enteric neurons.
AB  - Neuropeptides exert their diverse biological effects by interacting with G
      protein-coupled receptors (GPCRs). In this review we address the question, What
      regulates the ability of a target cell, in particular a neuron, to respond to a
      neuropeptide? Available evidence from studies of many GPCRs in reconstituted
      systems and transfected cell lines indicates that much of this regulation occurs
      at the level of the receptor and serves to alter the capacity of the receptor to
      bind ligands with high affinity and to couple to heterotrimeric G proteins.
      Although some of the knowledge gained from these studies is applicable to the
      regulation of neuropeptide receptors on neurons, at present there are far more
      questions than answers.

PMID- 9612258
TI  - Nitric oxide regulates energy metabolism and Bcl-2 expression in intestinal
      epithelial cells.
AB  - Nitric oxide (NO) inhibits the respiration of mitochondria and enteric bacteria,
      particularly under low O2 concentration, and induces apoptosis of various types
      of cells. To gain insight into the molecular role of NO in the intestine, we
      examined its effects on the respiration, Ca2+ status, and expression of Bcl-2 in
      cultured intestinal epithelial cells (IEC-6). NO reversibly inhibited the
      respiration of IEC-6 cells, especially under physiologically low O2
      concentration. Although NO elevated cytosolic Ca2+ as determined by the fura 2
      method, the cells were fairly resistant to NO. Kinetic analysis revealed that
      prolonged exposure to NO elevated the levels of Bcl-2 and suppressed the NO
      induced changes in Ca2+ status of the cells. Because Bcl-2 possesses
      antiapoptotic function, toxic NO effects might appear minimally in enterocytes
      enriched with Bcl-2. Thus NO might effectively exhibit its antibacterial action
      in anaerobic intestinal lumen without inducing apoptosis of Bcl-2-enriched
      mucosal cells.

PMID- 9612259
TI  - Reduction of acute and reactivated colitis in rats by an inhibitor of neutrophil
      activation.
AB  - Neutrophils have been implicated as major contributors to tissue injury in
      inflammatory bowel disease. In this study, we have assessed the effects of an
      inhibitor of neutrophil activation and adherence, NPC-18915 (4-?2-[2-(2
      benzofuranyl)phenyl]-(E)-ethenyl?benzoic acid sodium salt), in models of both
      acute and reactivated colitis. Acute colitis was induced by intracolonic
      administration of a hapten. In other rats, colitis was reactivated 6 wk after a
      bout of acute colitis by subcutaneous administration of the hapten. NPC-18915
      given during the first 4 days after induction of acute colitis significantly
      reduced tissue injury and the incidence of diarrhea and adhesions. When treatment
      of NPC-18915 was initiated after colitis was firmly established (48 h
      posthapten), it did not produce a significant effect. NPC-18915 was effective at
      significantly reducing colonic injury and granulocyte infiltration in the
      reactivated colitis model, and a similar effect could be observed in rats treated
      with antineutrophil serum. These results demonstrate that an inhibitor of
      neutrophil activation is effective in both acute and reactivated colitis,
      although in the former case, effectiveness is only seen when the drug is given
      before full establishment of colitis. These results also suggest that
      neutrophils, are a critical effector cell of hapten-induced colitis in the rat,
      particularly in the case of reactivated colitis.

PMID- 9612260
TI  - Intestinal fibroblasts regulate intestinal epithelial cell proliferation via
      hepatocyte growth factor.
AB  - Although the presence of subepithelial intestinal fibroblasts has been well
      recognized, the effects of fibroblasts on intestinal epithelial cell (IEC) growth
      are incompletely understood. In vitro studies were undertaken to evaluate the
      effects of fibroblasts on the proliferation of model IEC lines. IECs (Caco-2,
      T84, and IEC-6) were grown alone or in the presence of human intestinal (CCD-18),
      lung (CCD-37), or skin explant-derived fibroblasts. Cocultures were carried out
      directly on irradiated fibroblasts or by Transwell coculture technique with
      fibroblasts and epithelial cells separated by a porous filter. Cell proliferation
      was assessed by [3H]thymidine incorporation and cell counts. Hepatocyte growth
      factor (HGF) and c-met transcript expression in IECs and fibroblasts was examined
      by RT-PCR and Northern blotting; protein expression was evaluated by
      immunoblotting. Intestinal as well as lung and skin fibroblasts substantially
      stimulated proliferation of Caco-2, T84, and IEC-6 cells in both direct and
      Transwell cocultures. In addition, fibroblast-conditioned medium stimulated IEC
      proliferation, suggesting a paracrine mechanism. Anti-human HGF-neutralizing
      antibodies blocked the growth-promoting effects in both fibroblasts and
      fibroblast-conditioned medium. Recombinant human HGF dose dependently promoted
      IEC proliferation. HGF mRNA and protein expression was restricted to fibroblasts.
      High levels of c-met expression were found in Caco-2 and T84 cells; in contrast,
      expression in fibroblasts was weak. In summary, fibroblasts stimulate IEC
      proliferation through a paracrine mechanism mediated predominantly by HGF.

PMID- 9612261
TI  - Effect of ethanol on the structure and function of rabbit esophageal epithelium.
AB  - Epidemiological studies indicate a relationship between alcohol consumption and
      esophageal epithelial disease. We therefore sought the contribution of the direct
      effects of ethanol on esophageal epithelial structure and (transport and barrier)
      function. Epithelium from the rabbit was mounted in Ussing chambers and exposed
      luminally for 1 h to 1-40% ethanol. At concentrations of 1-5% potential
      difference (PD) increased, and at 10-40% PD decreased. The increase in PD with 1
      5% ethanol was accompanied by an increase in short-circuit current (Isc), and
      this increase in Isc could be blocked by ouabain pretreatment. The decrease in PD
      with 10-40% ethanol was associated with a decrease in electrical resistance (R),
      and this decrease in R was paralleled by an increase in transepithelial
      [14C]mannitol flux. Reversibility of these changes was limited at ethanol
      concentrations > or = 10%, and these were associated morphologically by patchy or
      diffuse tissue edema. Moreover, as with ethanol exposure in vitro, exposure in
      vivo produced dose-dependent changes in PD, Isc, R, and morphology. These
      observations indicate that exposure to ethanol in concentrations and under
      conditions reflecting alcohol consumption in humans can alter and impair
      esophageal epithelial transport and barrier functions. Such impairments are
      likely to contribute to the observed increase in risk of esophageal disease with
      regular consumption of alcoholic beverages.

PMID- 9612262
TI  - Involvement of the 5-HT3 receptor in CRH-induce defecation in rats.
AB  - We evaluated the possibility that serotonin (5-HT) mediates defecation induced by
      corticotropin-releasing hormone (CRH) exogenously administered or released from
      the central nervous system by stress via the 5-HT3 receptor in rats.
      Intracerebroventricular (i.c.v.) injection of CRH (1, 3, and 10 micrograms/rat)
      dose dependently increased the number of stools excreted in rats, whereas
      intravenous (i.v.) injection of up to 100 micrograms/kg CRH did not affect
      defecation. alpha-Helical CRH-(9-41) and 5-HT3 receptor antagonists ramosetron
      and azasetron inhibited CRH (10 micrograms i.c.v.)-induced defecation in a dose
      dependent manner with ED50 values of 4.3 micrograms/kg i.v., 3.8 micrograms/kg
      p.o., and 70.4 micrograms/kg p.o., respectively. alpha-Helical CRH-(9-41) also
      inhibited CRH-induced defecation by i.c.v. injection with an ED50 value of 0.078
      microgram/rat. In contrast, ramosetron and azasetron injected i.c.v. had no
      effect on CRH-induced defecation. alpha-Helical CRH-(9-41), ramosetron, and
      azasetron reduced defecation caused by restraint stress with ED50 values of 0.32,
      3.6, and 19.7 micrograms/kg i.v., respectively. These results indicate that CRH
      exogenously administered or released from the central nervous system by stress
      peripherally promotes the release of 5-HT, which in turn stimulates defecation
      through the 5-HT3 receptor.

PMID- 9612263
TI  - Role of mucosal mast cells in early vascular permeability changes of intestinal
      DTH reaction in the rat.
AB  - Previously, it was shown that depletion and stabilization of the mucosal mast
      cell around the time of challenge were very effective in reducing delayed-type
      hypersensitivity (DTH) reactions in the small intestine of the rat. The role of
      mucosal mast cells in the early component of intestinal DTH reaction was further
      investigated in this study. In vivo small intestinal vascular leakage and serum
      levels of rat mast cell protease II (RMCP II) were determined within 1 h after
      intragastric challenge of rats that had been sensitized with dinitrobenzene 5
      days before. A separate group of rats was used to study vasopermeability in
      isolated vascularly perfused small intestine after in vitro challenge. To
      investigate the effects of mast cell stabilization on the early events of the DTH
      reaction, doxantrazole was used. The influence of sensory nerves was studied by
      means of neonatal capsaicin-induced depletion of sensory neuropetides. Within 1 h
      after challenge, a significant increase in vascular permeability was found in
      vivo as well as in vitro. This was associated with a DTH-specific increase in
      RMCP II in the serum, indicating mucosal mast cell activation. In addition,
      doxantrazole treatment and caspaicin pretreatment resulted in a significant
      inhibition of the DTH-induced vascular leakage and an increase in serum RMCP II.
      These findings are consistent with an important role for mucosal mast cells in
      early vascular leakage changes of intestinal DTH reactions. In addition, sensory
      nervous control of mucosal mast cell activation early after challenge is
      demonstrated.

PMID- 9612264
TI  - TNF-alpha inhibits liver collagen-alpha 1(I) gene expression through a tissue
      specific regulatory region.
AB  - Although tumor necrosis factor-alpha (TNF-alpha) inhibits collagen-alpha 1(I)
      gene expression in cultured hepatic stellate cells, assessment of its effects on
      hepatic collagen expression is complicated by the confounding variables of tissue
      necrosis and inflammation. Therefore, we analyzed whether chronically elevated
      serum TNF-alpha affects constitutive hepatic collagen metabolism in vivo by
      inoculating nude mice with Chinese hamster ovary (CHO) cells secreting TNF-alpha
      (TNF-alpha mice) or with control CHO cells (control mice). Before the onset of
      weight loss, collagen synthesis and collagen gene expression were inhibited in
      the liver of TNF-alpha mice. In transgenic mice, after 8 h, TNF-alpha (500 ng at
      0 and 5 h) inhibited the liver expression of the collagen-alpha 1(I)-human growth
      hormone (hGH) transgene containing the first intron and -440 bp of the 5' region.
      Similarly, in cultured hepatic stellate cells isolated from these transgenic
      animals, the -440 bp collagen-alpha 1(I)-hGH transgene was responsive to TNF
      alpha treatment independent of the activation of these cells. Transfection
      studies in stellate cells allowed further characterization of this TNF-alpha
      responsive segment to -220 bp of the 5' region. Because in the skin the
      inhibitory effect of TNF-alpha involves a regulatory region of the collagen-alpha
      1(I) gene beyond -440 bp, we herein identify a novel tissue-specific regulation
      of collagen-alpha 1(I) gene by TNF-alpha.

PMID- 9612265
TI  - Effect of nitric oxide on calcium-activated potassium channels in colonic smooth
      muscle of rabbits.
AB  - Nitric oxide (NO) hyperpolarizes intestinal smooth muscle cells. This study was
      designed to determine the mechanism whereby NO activates KCa channels of circular
      smooth muscle of the rabbit colon. Transmural biopsies of the rabbit colon were
      stained for NADPH-diaphorase. Freshly dispersed circular smooth muscle cells were
      studied in the whole cell configuration, as well as in on-cell and excised inside
      out patch recording configurations, while KCa current and the activity of KCa
      channels, respectively, were monitored. NADPH-diaphorase-positive nerve fibers
      were found in both muscle layers. NO (1%) increased whole cell net outward
      current by 79% and hyperpolarized resting membrane voltage from -59 to -73 mV (n
      = 8 cells, P < 0.01). In the on-cell patch recording configuration. NO (0.5% or
      1%) in the bath increased NPo of KCa channels; charybdotoxin (125 nM) in the
      pipette solution blocked this effect. In the excised inside-out patch recording
      configuration, NO (1%) had no effect on NPo of KCa channels. In the on-cell patch
      recording configuration, methylene blue (1 microM) or cystamine (5 mM) in the
      bath solution decreased the effect of NO (1%) on NPo of KCa channels. NPo was
      increased by 8-bromo-cGMP (8-BrcGMP; 1 mM), a cGMP analog, and zaprinast (100
      microM), an inhibitor of cGMP phosphodiesterase. These data suggest that NO
      increased whole cell outward K+ current by activating KCa channels through a cGMP
      pathway.

PMID- 9612266
TI  - In vivo three-dimensional EPR imaging of nitric oxide production from isosorbide
      dinitrate in mice.
AB  - Recently, in vivo electron paramagnetic resonance (EPR) spectroscopy and imaging
      have been widely used to investigate free radical distribution and metabolism in
      tissues, organs, and whole body of small animals. Endogenous nitric oxide (NO) is
      an attractive target of this method. In the present study, NO production from a
      nitrovasodilator, isosorbide dinitrate (ISDN), in live mice was investigated by
      in vivo EPR spectroscopy and imaging combined with the spin-trapping technique. A
      highly water-soluble Fe complex with N-(dithiocarboxy)sarcosine (DTCS) was used
      as an NO-trapping agent. Mice received [14N]-ISDN, and the Fe-DTCS complex
      subcutaneously exhibited the characteristic triplet EPR signal of the NO adduct
      [14NO-Fe(DTCS)2]2-. Using [15N]ISDN instead of [14N]ISDN, we were able to observe
      that the doublet EPR signal stemmed from the 15NO adduct, which directly
      demonstrated that NO was produced from ISDN. The three-dimensional EPR images of
      the upper abdomen of living mice showed that the NO adducts were distributed in
      the liver and the kidneys. This EPR image combined with the ex vivo EPR
      measurements of the blood suggested that NO production from ISDN occurred in the
      liver in this experimental condition.

PMID- 9612267
TI  - Localization and significance of pp55, a gastric mucosal membrane protein with
      tyrosine kinase activity.
AB  - In Fischer 344 rats, induction of gastric mucosal proliferative activity, whether
      the result of aging or injury or occurring after administration of epidermal
      growth factor, gastrin, or bombesin, is associated with a rise in tyrosine kinase
      activity and tyrosine phosphorylation of several mucosal proteins, including a
      protein with a molecular mass of 53-55 kDa. We hypothesized that this
      phosphotyrosine membrane protein (referred to as pp55) may play a role in
      regulating gastric mucosal cell proliferation and differentiation. Purification
      and subsequent immunoprecipitation studies now show that pp55 is a tyrosine
      kinase. In addition, the enzyme activity in the gastric mucosa is found to be
      fourfold higher in aged rats than in young rats. Incubation of gastric mucosal
      membranes with transforming growth factor-alpha (2 x 10(-8) M) stimulates
      tyrosine kinase activity of pp55. Immunolocalization studies reveal that pp55
      immunoreactivity is predominantly present in mucous cells that are located just
      above the proliferative zone and spasmolytic peptide-immunoreactive mucous neck
      cells. Tyrosine kinase activity as well as expression of pp55 are also greatly
      increased in the gastric mucosa after hypertonic saline-induced injury, a
      condition that results in stimulation of surface mucosal cell proliferation and
      differentiation. Our current data suggest that pp55 is a tyrosine kinase, likely
      localized to pre-surface cells. The presence of pp55 in pre-surface mucous cells
      and the expression and tyrosine kinase activity of this protein, which can be
      stimulated during mucosal cell proliferation and differentiation, strongly
      suggest a role for pp55 in differentiation of gastric surface mucous cells.

PMID- 9612268
TI  - MUC5B is the prominent mucin in human gallbladder and is also expressed in a
      subset of colonic goblet cells.
AB  - To elucidate the roles of human gallbladder mucin (HGBM), such as in gallstone
      formation and cytoprotection, it is essential to identify HGBM and study its
      expression. This was performed by metabolic labeling, Western blotting,
      immunohistochemistry, and RT-PCR. In a large number of individuals, antibodies
      against purified HGBM and against MUC5B detected a mucin precursor (approximately
      470 kDa) in the gallbladder and colon, but not in the small intestine. In the
      gallbladder, Western blotting using specific anti-MUC5B antibodies showed that
      this mucin precursor represented an identical mucin, MUC5B. RT-PCR experiments
      demonstrated a similar tissue distribution pattern of MUC5B mRNA.
      Immunohistochemistry with anti-HGBM and anti-MUC5B showed staining in gallbladder
      epithelial cells and colonic goblet cells in the crypt base, but not in the small
      intestine; double labeling showed that HGBM was located in small granules within
      goblet cells, colocalizing to MUC2-containing goblet cells. Metabolic labeling
      demonstrated the secretion of mature MUC5B in the colon. Conclusively, MUC5B is
      identified as the prominent HGBM and is also expressed and secreted in the colon.

PMID- 9612269
TI  - Polyamines are required for microtubule formation during gastric mucosal healing.
AB  - Polyamines are essential for the repair of gastric and duodenal erosions.
      Concentrated NaCl (3.4 M) given intragastrically damages the oxyntic gland mucosa
      and increases the activity of gastric mucosal ornithine decarboxylase (ODC), the
      first rate-limiting enzyme in polyamine synthesis. The nature of the process of
      restitution of damaged mucosa is not well known, except that cell migration and
      the actin cytoskeleton play a prominent role. Microtubules are cytoskeletal
      components essential for cell migration. The present investigation determines the
      relationship between polyamines, the distribution of microtubules, and gastric
      healing in mucosa damaged with hypertonic NaCl solution. Rats were fasted for 22
      h and then given 1.0 ml of 3.4 M NaCl intragastrically. Animals were killed 1, 2,
      4, 8, and 10 h after 3.4 M NaCl. The oxyntic gland mucosa was removed, and
      tubulin was visualized by immunofluorescence. Microtubule density was increased
      around and below the damaged mucosa in the upper one-third of the glandular
      epithelium at 2 and 4 h and returned to near control levels by 10 h. In rats
      damaged with 3.4 M NaCl and pretreated intraperitoneally with alpha
      difluoromethylornithine (DFMO), a specific inhibitor of ODC, microtubule content
      was reduced significantly at all time points after NaCl treatment. Addition of
      spermidine after pretreatment with DFMO and 3.4 M NaCl significantly prevented
      the effects of DFMO. Colchicine, a potent microtubule-disrupting drug,
      significantly delayed normal gastric mucosal healing with no effect on ODC
      activity. These data show that polyamines influence the distribution of
      microtubules during damage in vivo and indicate a partial mechanism for the
      dependency of mucosal healing on polyamines.

PMID- 9612270
TI  - Nitric oxide suppresses a Ca(2+)-stimulated Cl- current in smooth muscle cells of
      opossum esophagus.
AB  - Nitric oxide (NO) hyperpolarizes visceral smooth muscles. Using the patch-clamp
      technique, we investigated the possibility that NO-mediated hyperpolarization in
      the circular muscle of opossum esophagus results from the suppression of a Ca(2+)
      stimulated Cl- current. Smooth muscle cells were dissociated from the circular
      layer and bathed in high-K+ Ca(2+)-EGTA-buffered solution. Macroscopic ramp
      currents were recorded from cell-attached patches. Contaminating K(+)-channel
      currents were blocked with tetrapentylammonium chloride (200 microM) added to all
      solutions. Raising bath Ca2+ concentration above 150 nM in the presence of A
      23187 (10 microM) activated a leak current (IL-Ca) with an EC50 of 1.2 microM at 
      100 mV. The reversal potential (Erev) of IL-Ca (-8.5 +/- 1.8 mV, n = 8) was
      significantly different (P < 0.05) from Erev of the background current (+4.2 +/-
      1.2 mV, n = 8). Equimolar substitution of 135 mM Cl- in the pipette solution with
      gluconate significantly shifted Erev of IL-Ca to +16.6 +/- 3.4 mV (n = 4) (P <
      0.05 compared with background), whereas replacement of total Na+ with Tris+
      suppressed IL-Ca but did not affect Erev (-15 +/- 3 mV, n = 3; P > 0.05). IL-Ca
      was inhibited by DIDS (500 microM). Diethylenetriamine-NO adduct (200 microM), a
      NO donor, and 8-bromo-cGMP (200 microM) suppressed IL-Ca by 59 +/- 15% (n = 5)
      and 62 +/- 21% (n = 4) at -100 mV, respectively. We conclude that in opossum
      esophageal smooth muscle NO-mediated hyperpolarization may be produced by
      suppression of a Ca(2+)-stimulated Cl(-)-permeable conductance via formation of
      cGMP.

PMID- 9612271
TI  - Secretory PAF-acetylhydrolase of the rat hepatobiliary system: characterization
      and partial purification.
AB  - Hepatocytes and Kupffer cells in primary culture both secrete plasma-type
      platelet-activating factor-acetylhydrolase (pPAF-AH) into serum-free culture
      medium. The rate of secretion of pPAF-AH by Kupffer cells was 20 to 25 times
      higher than from hepatocytes, and Kupffer cells expressed a higher level of pPAF
      AH mRNA than did hepatocytes. Purified liver cell-secreted pPAF-AH exhibited a
      major protein band of 65-67 kDa on SDS-PAGE; this was the band predominantly
      labeled when the enzyme catalytic center was reacted with
      [3H]diisopropylfluorophosphate ([3H]DFP). Rat bile collected from cannulated bile
      ducts contained significant PAF-AH activity, and bile samples possessed a
      prominent band at 30-32 kDa, which was the exclusive target for [3H]DFP.
      Experiments using tunicamycin, an inhibitor of N-linked glycosylation, and
      endoglycosidase H suggested that pPAF-AH secreted constitutively by cultured
      hepatocytes and Kupffer cells is glycosylated. The present study supports the
      notion that hepatic secretion of pPAF-AH into the blood contributes to the
      regulation of PAF and oxidized phospholipid levels in the circulation, whereas
      secretion of PAF-AH into the bile may allow hepatic control of these phospholipid
      signaling molecules in the gastrointestinal tract.

PMID- 9612272
TI  - Molecular identification of a component of delayed rectifier current in
      gastrointestinal smooth muscles.
AB  - Kv2.2, homologous to the shab family of Drosophila voltage-gated K+ channels, was
      isolated from human and canine colonic circular smooth muscle-derived mRNA.
      Northern hybridization analysis performed on RNA prepared from tissues and RT-PCR
      performed on RNA isolated from dispersed and selected smooth muscle cells
      demonstrate that Kv2.2 is expressed in smooth muscle cells found in all regions
      of the canine gastrointestinal (GI) tract and in several vascular tissues.
      Injection of Kv2.2 mRNA into Xenopus oocytes resulted in the expression of a
      slowly activating K+ current (time to half maximum current, 97 +/- 8.6 ms)
      mediated by 15 pS (symmetrical K+) single channels. The current was inhibited by
      tetraethylammonium (IC50 = 2.6 mM), 4-aminopyridine (IC50 = 1.5 mM at +20 mV),
      and quinine (IC50 = 13.7 microM) and was insensitive to charybdotoxin. Low
      concentrations of quinine (1 microM) were used to preferentially block the slow
      component of the delayed rectifier current in native colonic myocytes. These data
      suggest that Kv2.2 may contribute to this current in native GI smooth muscle
      cells.

PMID- 9612273
TI  - Canine small bowel motor patterns and contractions are not neurally regulated
      during enteric nutrient infusion.
AB  - The aims of this study were to determine the effects of duodenal and jejunoileal
      nutrient infusions on small intestinal motor patterns and intestinal contractions
      in neurally intact and neurally isolated small bowel. Fifteen dogs were prepared
      with duodenal and jejunal infusion and manometry catheters and a diverting
      jejunal cannula. Ten of the dogs underwent in situ neural isolation of the
      jejunoileum. A mixed nutrient meal (0.5 kcal/ml) was infused into the duodenum or
      jejunum at 3 ml/min for 5 h. Control experiments involved infusion of a balanced
      salt solution. Manometric data collected on-line to a microcomputer were analyzed
      for direction, distance, and velocity of spread of single pressure waves (SPW)
      and clustered contractions. Isolated duodenal and jejunoileal nutrient infusions
      inhibited the fasting motor pattern in neurally intact and neurally isolated
      small bowel. Motor activity (motility index) increased slightly during nutrient
      infusion within groups, but there were few differences between groups. Neither
      neural isolation nor nutrient infusion had a consistent effect on spread of SPW
      or migration of clustered contractions. Isolated duodenal and jejunoileal
      nutrient infusions in the dog inhibit fasting motor patterns and increase motor
      activity slightly but have little effect on characteristics of individual and
      clustered contractions. Extrinsic innervation to the jejunoileum or intrinsic
      neural continuity of the jejunum with the duodenum had little effect on single or
      grouped contractions. Although the changes in motor activity demonstrated in this
      study appear small, alterations in intestinal transit and absorption may still
      occur and may be of importance physiologically.

PMID- 9612274
TI  - Novel properties of hepatic canalicular reduced glutathione transport revealed by
      radiation inactivation.
AB  - Transport of GSH at the canalicular pole of hepatocytes occurs by a facilitative
      carrier and can account for approximately 50% of total hepatocyte GSH efflux. A
      low-affinity unit with sigmoidal kinetics accounts for 90% of canalicular
      transport at physiological GSH concentrations. A low-capacity transporter with
      high affinity for GSH has also been reported. It is not known whether the same or
      different proteins mediate low- and high-affinity GSH transport, although they do
      differ in inhibitor specificity. The bile of rats with a mutation in the
      canalicular multispecific organic anion transporter (cMOAT or MRP-2, a 170-kDa
      protein) is deficient in GSH, implying that cMOAT may transport GSH. However,
      transport of GSH in canalicular membrane vesicles (CMV) from these mutant rats
      remains intact. We examined the functional size of the two kinetic components of
      GSH transport by radiation inactivation of GSH uptake in rat hepatic CMV. High
      affinity transport of GSH was inactivated as a single exponential function of
      radiation dose, yielding a functional size of approximately 70 kDa. In contrast,
      low-affinity canalicular GSH transport exhibited a complex biexponential response
      to irradiation, characterized by an initial increase followed by a decrease in
      GSH transport. Inactivation analysis yielded a approximately 76-kDa size for the
      low-affinity transporter. The complex inactivation indicated that the low
      affinity transporter is associated with a larger protein of approximately 141
      kDa, which masked approximately 80% of the potential transport activity in CMV.
      Additional studies, using inactivation of leukotriene C4 transport, yielded a
      functional size of approximately 302 kDa for cMOAT, indicating that it functions
      as a dimer.

PMID- 9612275
TI  - Selecting agent hygromycin B alters expression of glucose-regulated genes in
      transfected Caco-2 cells.
AB  - Incorporation into plasmids of genes conferring resistance to aminoglycoside
      antibiotics such as hygromycin B is currently utilized for selection in
      experiments involving gene transfer in eukaryotic cells. Using a subclone of Caco
      2 cells stably transfected with an episomal plasmid containing the hygromycin
      resistance gene, we observed that transformed cells subcultured in the presence
      of hygromycin B exhibit, compared with the same cells subcultured in antibiotic
      free medium, a sixfold increase in the rates of glucose consumption and lactic
      acid production and dramatic changes, at mRNA and protein level, of the
      expressions of sucrase-isomaltase and hexose transporter GLUT-2, which are
      downregulated, contrasting with an upregulation of hexose transporter GLUT-1.
      This occurs without significant modifications of the differentiation status of
      the cells, as demonstrated by the normal expression of villin, ZO-1, dipeptidyl
      peptidase IV, or Na(+)-K(+)-ATPase. The plasmid copy number is, however, the
      same, whether or not the cells are cultured in the presence of hygromycin B.
      These results draw attention to the need to consider antibiotic-dependent
      alterations of metabolism and gene expression in transfection experiments.

PMID- 9612276
TI  - Effect of CCK on proximal gastric motor function in humans.
AB  - We have studied the effect of CCK on proximal gastric motor function in humans.
      Seven healthy volunteers participated in three experiments performed in random
      order during continuous intravenous infusion of 1) saline (control), 2) 0.5
      IDU.kg-1.h-1 CCK, and 3) 1.0 IDU.kg-1.h-1 CCK. Proximal gastric mechanics were
      measured by an electronic barostat, and abdominal symptoms were scored by visual
      analog scales. Infusion of 0.5 and 1.0 IDU.kg-1.h-1 CCK resulted in plasma CCK
      levels (RIA) in the postprandial range. CCK induced gastric relaxation; at 2 mmHg
      above intra-abdominal pressure the intragastric volume during 1.0 IDU.kg-1.h-1
      CCK was significantly increased over saline (363 +/- 44 vs. 195 +/- 34 ml; P <
      0.01) but not during 0.5 IDU.kg-1.h-1 CCK (195 +/- 14 ml; not significant).
      During both isovolumetric and isobaric distensions, 1.0 IDU.kg-1.h-1 CCK
      significantly (P < 0.05) increased proximal gastric compliance compared with
      saline. However, 0.5 IDU.kg-1.h-1 CCK had no significant effect on gastric
      compliance. During volume distensions, but not during fixed pressure distensions,
      1.0 IDU.kg-1.h-1 CCK significantly (P < 0.05) reduced visceral perception. These
      results suggest that in humans CCK may have a physiological role in regulating
      proximal gastric mechanics.

PMID- 9612277
TI  - Subepithelial fibroblast cell lines from different levels of gut axis display
      regional characteristics.
AB  - The intestine is characterized by morphofunctional differences along the
      proximodistal axis. The aim of this study was to derive mesenchymal cell lines
      representative of the gut axis. We isolated and cloned rat intestinal
      subepithelial myofibroblasts raised from 8-day proximal jejunum, distal ileum,
      and proximal colon lamina propria. Two clonal cell lines from each level of the
      gut were characterized. They 1) express the specific markers vimentin, smooth
      muscle alpha-actin, and smooth muscle myosin heavy chain, revealed by
      immunofluorescence microscopy and 2) distinctly support endodermal cell growth in
      a coculture model, depending on their regional origin, and 3) the clones raised
      from the various proximodistal regions maintain the same pattern of morphogenetic
      and growth and/or differentiation factor gene expression as in vivo: hepatocyte
      growth and/or scatter factor and transforming growth factor-beta 1 mRNAs analyzed
      by RT-PCR were more abundant, in the colon and ileal clones and mucosal
      connective tissue, respectively. In addition, epimorphin mRNA studied by Northern
      blot was also the highest in one ileal clone, in which it was selectively
      upregulated by all-trans retinoic acid (RA) treatment. Epimorphin expression in
      isolated 8-day intestinal lamina propria was higher in the distal small intestine
      and proximal colon than in the proximal small intestine. In conclusion, we
      isolated and characterized homogeneous cell subtypes that can now be used to
      approach the molecular regulation of the epithelium-mesenchyme-dependent regional
      specificity along the gut.

PMID- 9612278
TI  - Peptidergic and cholinergic neurons and mediators in peptone-induced
      gastroprotection: role of cyclooxygenase-2.
AB  - This study investigates the neural pathways, mediators, and cyclooxygenase
      isoenzymes involved in the gastroprotection conferred by peptone in rats.
      Intragastric perfusion with 8% peptone protected against gross and histological
      damage induced by subsequent perfusion with 50% ethanol. The gastroprotective
      effect of peptone was near maximally inhibited by gastrin immunoneutralization,
      inactivation of capsaicin-sensitive afferent neurons, calcitonin gene-related
      peptide (CGRP) immunoneutralization, blockade of gastrin receptors, CGRP,
      bombesin/gastrin-releasing peptide (GRP), or somatostatin receptors, and by the
      nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester and was
      partially (46%) counteracted by atropine. Indomethacin and the selective
      cyclooxygenase-2 inhibitors NS-398 and L-745,337 dose dependently (50% inhibitory
      dose, 4.2, 0.8, and 1.5 mg/kg, respectively) attenuated the peptone-induced
      protection. Dexamethasone was ineffective. These results indicate that protective
      effects of peptone involve endogenous gastrin and possibly somatostatin and are
      mediated by capsaicin-sensitive afferent, cholinergic, and bombesin/GRP neurons.
      CGRP, NO, and prostaglandins participate as essential mediators. The study
      provides evidence that prostaglandins derived from a constitutive cyclooxygenase
      2 contribute to mucosal defense in the presence of ulcerogens and thus
      participate in homeostatic functions of the stomach.

PMID- 9612279
TI  - Central CRF inhibits gastric emptying of a nutrient solid meal in rats: the role
      of CRF2 receptors.
AB  - Corticotropin-releasing factor (CRF)-related peptides exhibit different affinity
      for the receptor subtypes 1 and 2 cloned in the rat brain. We investigated, in
      conscious rats, the effects of intracisternal (i.c.) injection of CRF (rat/human)
      on the 5-h rate of gastric emptying of a solid nutrient meal (Purina chow and
      water ad libitum for 3 h) and the CRF receptor subtype involved. CRF, urotensin I
      (suckerfish), and sauvagine (frog) injected i.c. inhibited gastric emptying in a
      dose-dependent manner, with ED50 values of 0.31, 0.13, and 0.08 microgram/rat,
      respectively. Rat CRF-(6-33) (0.1-10 micrograms i.c.) had no effect. The
      nonselective CRF1 and CRF2 receptor antagonist, astressin, injected i.c.
      completely blocked the inhibitory effect of i.c. CRF, urotensin I, and sauvagine
      with antagonist-to-agonist ratios of 3:1, 10:1, and 16:1, respectively. The CRF1
      selective receptor antagonist NBI-27914 injected i.c. at a ratio of 170:1 had no
      effect. These data show that central CRF and CRF-related peptides are potent
      inhibitors of gastric emptying of a solid meal with a rank order of potency
      characteristic of the CRF2 receptor subtype affinity (sauvagine > urotensin I >
      CRF). In addition, the reversal by astressin but not by the CRF1-selective
      receptor antagonist further supports the view that the CRF2 receptor subtype is
      primarily involved in central CRF-induced delayed gastric emptying.

PMID- 9612280
TI  - PKC activation is required by EGF-stimulated Na(+)-H+ exchanger in human pleural
      mesothelial cells.
AB  - Epidermal growth factor (EGF) stimulates the Na(+)-H+ exchanger, leading to
      enhanced cell proliferation. In human pleural mesothelial cells (PMCs), the
      intracellular signaling mechanism mediating the EGF-induced stimulation of the
      Na(+)-H+ exchanger has not yet been identified. Using a pH-sensitive fluorescent
      probe, 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein, to measure changes in
      intracellular pH (pHi), we found that 1) EGF and 12-O-tetradecanoylphorbol 13
      acetate (TPA; a phorbol ester) both stimulate the ethylisopropyl amiloride
      sensitive Na(+)-H+ exchanger; 2) TPA-induced alkalosis can be blocked by protein
      kinase C (PKC) inhibitors (chelerythrine and staurosporine) or by PKC down
      regulation, indicating that PKC activation is involved in the stimulation of the
      Na(+)-H+ exchanger. However, TPA-induced alkalosis is not blocked by tyrosine
      kinase inhibitors; and 3) the stimulatory effect of EGF on the Na(+)-H+ exchanger
      acts via stimulation of tyrosine kinase-receptor activity because it is inhibited
      by tyrosine kinase inhibitors (genistein, lavendustin A, and herbimycin A). It
      also involves PKC activation because EGF-induced alkalosis was blocked by PKC
      inhibitors. These results suggest that PKC activation is one of the downstream
      signals for EGF-induced activation of the Na(+)-H+ exchanger in primary cultures
      of human pleural mesothelial cells.

PMID- 9612281
TI  - Intracellular uptake of recombinant superoxide dismutase after intratracheal
      administration.
AB  - We have previously demonstrated that recombinant human copper-zinc superoxide
      dismutase (rhCu,ZnSOD) is rapidly incorporated into cells of airways, respiratory
      bronchioles, and alveoli after intratracheal administration. The present study
      examines whether this cellular uptake is specific for rhCu,ZnSOD or whether other
      proteins are similarly incorporated into lung cells. Twenty-two newborn piglets
      (2-3 days old, 1.2-2.0 kg) were intubated and mechanically ventilated. Eight
      piglets received fluorescently labeled recombinant human manganese superoxide
      dismutase (rhMnSOD), six received fluorescently labeled albumin, two received
      free (unbound) fluorescent label intratracheally, and two piglets served as
      untreated controls. To determine whether endogenous surfactant was important in
      the process of intracellular uptake, four additional piglets were made surfactant
      deficient by repeated bronchoalveolar lavage and then given rhCu,ZnSOD
      intratracheally. All animals were killed after 30-60 min. Lung sections were
      examined blindly by laser confocal microscopy. Similar to our previous
      observations with rhCu,ZnSOD, intracellular uptake of rhMnSOD and albumin was
      noted throughout the lung. The free label did not localize intracellularly. The
      uptake of proteins did not appear to be affected by surfactant deficiency.
      rhMnSOD administration was associated with a greater than twofold increase in
      lung MnSOD activity. Data suggest that the cellular uptake of antioxidants and
      other proteins in the lung may reflect a nonspecific host defense system for
      clearing proteins from the lumen of airways and alveoli.

PMID- 9612282
TI  - VEGF induces hyperpermeability by a direct action on endothelial cells.
AB  - Vascular endothelial growth factor (VEGF) is a key regulator of vasculo- and
      angiogenesis. Earlier studies demonstrated a permeability-increasing effect of
      VEGF in skin tests, leading to its other name, vascular permeability factor. We
      wondered whether VEGF-induced hyperpermeability was a direct effect of VEGF on
      endothelial cells and studied the permeability of human and porcine endothelial
      cell monolayers in a well-characterized in vitro system. VEGF increased the
      hydraulic conductivity up to 20-fold and simultaneously decreased the albumin
      reflection coefficient. This effect occurred after a delay of 150 min, although
      VEGF-induced early endothelial cell activation was verified by enhanced inositol
      phosphate accumulation within 5 min and increased P-selectin expression within 15
      min. Platelet-derived growth factor and granulocyte-macrophage colony-stimulating
      factor, two endothelial cell nonspecific mitogens, also stimulated
      phosphatidylinositol metabolism and P-selectin expression; however, they had no
      effect on endothelial permeability. The increase in intracellular cyclic
      nucleotide levels of human endothelial monolayers abolished VEGF-induced
      endothelial hyperpermeability. In summary, VEGF increased endothelial
      permeability by a direct action on endothelial cells. Based on the pattern of
      endothelial cell activation by growth factors, VEGF appears to be a unique
      stimulus.

PMID- 9612283
TI  - Ascorbate-mediated transplasma membrane electron transport in pulmonary arterial
      endothelial cells.
AB  - Pulmonary endothelial cells are capable of reducing certain electron acceptors at
      the luminal plasma membrane surface. Motivation for studying this phenomenon
      comes in part from the expectation that it may be important both as an
      endothelial antioxidant defense mechanism and in redox cycling of toxic free
      radicals. Pulmonary arterial endothelial cells in culture reduce the oxidized
      forms of thiazine compounds that have been used as electron acceptor probes for
      studying the mechanisms of transplasma membrane electron transport. However, they
      reduce another commonly studied electron acceptor, ferricyanide, only very slowly
      by comparison. In the present study, we examined the influence of ascorbate
      [ascorbic acid (AA)] and dehydroascorbate [dehydroascorbic acid (DHAA)] on the
      ferricyanide and thiazine reductase activities of the bovine pulmonary arterial
      endothelial cell surface. The endothelial cells were grown on microcarrier beads
      so that the reduction of ferricyanide and methylene blue could be studied
      colorimetrically in spectrophotometer cuvettes and in flow-through cell columns.
      The ferricyanide reductase activity could be increased 80-fold by adding DHAA to
      the medium, with virtually no effect on methylene blue reduction. The DHAA effect
      persisted after the DHAA was removed from the medium. AA also stimulated the
      ferricyanide reductase activity but was less potent, and the relative potencies
      of AA and DHAA correlated with their relative rates of uptake by the cells. The
      results are consistent with the hypothesis that AA is an intracellular electron
      donor for an endothelial plasma membrane ferricyanide reductase and that the
      stimulatory effect of DHAA is the result of increasing intracellular AA. Adding
      sufficient DHAA to markedly increase extracellular ferricyanide reduction had
      little effect on the plasma membrane methylene blue reductase activity,
      suggesting that pulmonary arterial endothelial cells have at least two separate
      transplasma membrane electron transport systems.

PMID- 9612284
TI  - Modulation of lung liquid clearance by isoproterenol in rat lungs.
AB  - beta-Adrenergic agonists have been reported to increase lung liquid clearance by
      stimulating active Na+ transport across the alveolar epithelium. We studied
      mechanisms by which beta-adrenergic isoproterenol (Iso) increases lung liquid
      clearance in isolated perfused fluid-filled rat lungs. Iso perfused through the
      pulmonary circulation at concentrations of 10(-4) to 10(-8) M increased lung
      liquid clearance compared with that of control lungs (P < 0.01). The increase in
      lung liquid clearance was inhibited by the beta-antagonist propranolol (10(-5)
      M), the Na(+)-channel blocker amiloride (10(-4) M), and the antagonist of Na-K
      ATPase, ouabain (5 x 10(-4) M). Colchicine, which inhibits cell microtubular
      transport of ion-transporting proteins to the plasma membrane, blocked the
      stimulatory effects of Iso on active Na+ transport, whereas the isomer
      lumicolchicine, which does not affect cell microtubular transport, did not
      inhibit Na+ transport. In parallel with these changes, the Na-K-ATPase alpha 1
      subunit protein abundance and activity increased in alveolar type II cells
      stimulated by 10(-6) M Iso. Colchicine blocked the stimulatory effect of Iso and
      the recruitment of Na-K-ATPase alpha 1-protein to the basolateral membrane of
      alveolar type II cells. Accordingly, Iso increased active Na+ transport and lung
      liquid clearance by stimulation of beta-adrenergic receptors and probably by
      upregulation of apical Na+ channels and basolateral Na-K-ATPase mechanisms.
      Recruitment from intracellular pools and microtubular transport of Na+ pumps to
      the plasma membrane participate in beta-adrenergic stimulation of lung liquid
      clearance in rat lungs.

PMID- 9612285
TI  - PDGF-induced glycosaminoglycan synthesis is mediated via phosphatidylinositol 3
      kinase.
AB  - Platelet-derived growth factor (PDGF)-BB has been shown previously to increase
      glycosaminoglycan (GAG) synthesis but not DNA synthesis in freshly isolated fetal
      lung fibroblasts. In the present study, we found that PDGF-BB also enhanced 35SO4
      incorporation into the small, soluble proteoglycan biglycan without affecting
      biglycan's core protein mRNA expression, suggesting that PDGF-BB mainly affects
      GAG chain elongation and/or sulfation. PDGF-BB-stimulated GAG synthesis was
      abrogated by tyrphostin 9, a PDGF receptor-associated tyrosine kinase inhibitor,
      implying that the stimulatory effect is mediated via the PDGF beta-receptor
      (PDGFR). The intracellular signal transduction pathways that mediate PDGF-BB
      stimulated GAG synthesis in fetal lung fibroblasts were investigated. On ligand
      induced tyrosine phosphorylation, PDGFR associated with phospholipase C (PLC)
      gamma 1, Ras GTPase activating protein (RasGAP), and phosphatidylinositol 3
      kinase (PI3K) but not with the Syp-growth factor receptor-bound protein 2-Son of
      Sevenless complex. Association of PDGFR with PLC-gamma 1 and RasGAP followed by
      their tyrosine phosphorylation failed, however, to activate PLC-gamma 1, protein
      kinase C (PKC), and Ras. Neither a PLC-gamma inhibitor, U-73122; a PKC inhibitor,
      calphostin C; nor a mitogen-activated protein kinase kinase inhibitor, PD-98059,
      inhibited PDGF-BB-induced GAG synthesis. In contrast, PDGF-BB stimulation
      triggered PDGFR-associated PI3K activity. Both PDGF-BB-induced PI3K activation
      and GAG synthesis were abolished by the PI3K inhibitors wortmannin and LY-294002.
      The results suggest that PI3K is a downstream mediator of PDGF-BB-stimulated GAG
      synthesis in fetal rat lung fibroblasts.

PMID- 9612287
TI  - Nitro blue tetrazolium inhibits but does not mimic hypoxic vasoconstriction in
      isolated rabbit lungs.
AB  - It has been suggested that hypoxic pulmonary vasoconstriction (HPV) may mainly
      proceed via loss of normoxic vasodilation, forwarded by tonic O2-dependent
      formation of nitric oxide and superoxide (23). Both agents may stimulate
      guanylate cyclase, the latter via conversion to hydrogen peroxide and formation
      of compound I with catalase. We probed this hypothesis in perfused rabbit lungs,
      employing the superoxide scavengers superoxide dismutase (SOD), 4,5-dihydroxy-1,3
      benzene disulfonic acid (Tiron), and nitro blue tetrazolium (NBT) and the
      catalase inhibitor aminotriazole (AT). NBT turned out to be a potent dose
      dependent inhibitor of HPV in a concentration range of 200 nM to 1 microM, and
      superimposable dose-inhibition curves were obtained when lung synthesis of nitric
      oxide and vasodilatory prostanoids was preblocked by NG-monomethyl-L-arginine (L
      NMMA) and acetylsalicylic acid (ASA). The NBT effect was specific because no
      inhibition in the vasoconstrictor responses to the stable thromboxane analog U
      46619 and angiotensin II was observed. In contrast, SOD and Tiron were
      ineffective. AT exerted nonspecific inhibition of the hypoxia- and chemical
      vasoconstrictor-induced pressor responses. When applied under normoxic
      conditions, however, NBT alone or coapplied with L-NMMA or ASA, both for blockage
      of parallel vasodilatory pathways, did not mimic the hypoxia-induced
      vasoconstrictor response. In conclusion, the present study supports an important
      role for superoxide in the basic mechanism of HPV, but it questions the concept
      that loss of tonic vasorelaxation via this pathway is the underlying event in
      rabbit lungs. The mechanisms relating O2 tension-dependent superoxide and
      hydrogen peroxide generation to the vasoconstrictor event occurring in HPV remain
      to be further elucidated.

PMID- 9612286
TI  - Apoptosis and DNA damage in type 2 alveolar epithelial cells cultured from
      hyperoxic rats.
AB  - Apoptosis is a genetically controlled cellular response to developmental stimuli
      and environmental insult that culminates in cell death. Sublethal hyperoxic
      injury in rodents is characterized by a complex but reproducible pattern of lung
      injury and repair during which the alveolar surface is damaged, denuded, and
      finally repopulated by type 2 alveolar epithelial cells (AEC2). Postulating that
      apoptosis might occur in AEC2 after hyperoxic injury, we looked for the hallmarks
      of apoptosis in AEC2 from hyperoxic rats. A pattern of increased DNA end
      labeling, DNA laddering, and induction of p53, p21, and Bax proteins, strongly
      suggestive of apoptosis, was seen in AEC2 cultured from hyperoxic rats when
      compared with control AEC2. In contrast, significant apoptosis was not detected
      in freshly isolated AEC2 from oxygen-treated rats. Thus the basal culture
      conditions appeared to be insufficient to ensure the ex vivo survival of AEC2
      damaged in vivo. The oxygen-induced DNA strand breaks were blocked by the
      addition of 20 ng/ml of keratinocyte growth factor (KGF) to the culture medium
      from the time of plating and were partly inhibited by Matrigel or a soluble
      extract of Matrigel. KGF treatment resulted in a partial reduction in the
      expression of the p21, p53, and Bax proteins but had no effect on DNA laddering.
      We conclude that sublethal doses of oxygen in vivo cause damage to AEC2,
      resulting in apoptosis in ex vivo culture, and that KGF can reduce the oxygen
      induced DNA damage. We speculate that KGF plays a role as a survival factor in
      AEC2 by limiting apoptosis in the lung after acute hyperoxic injury.

PMID- 9612288
TI  - Metal-dependent expression of ferritin and lactoferrin by respiratory epithelial
      cells.
AB  - Increased availability of catalytically active metal has been associated with an
      oxidative injury. The sequestration of transition metals within intracellular
      ferritin confers an antioxidant function to this protein. Such storage by
      ferritin requires that the metal be transported across a cell membrane. We tested
      the hypothesis that, in response to in vitro exposures to catalytically active
      metal, respiratory epithelial cells increase the production of lactoferrin and
      ferritin to bind, transport, and store this metal with their coordination sites
      fully complexed. Residual oil fly ash is an emission source air pollution
      particle with biological effects that, both in vitro and in vivo, correspond with
      its metal content. Cell cultures were exposed to 0-200 micrograms/ml of oil fly
      ash for 2 and 24 h. Concentrations of ferritin and lactoferrin mRNA were
      estimated by reverse transcription-polymerase chain reaction, and concentrations
      of ferritin and lactoferrin proteins were measured in parallel. mRNA for ferritin
      did not change with exposure to oil fly ash. However, ferritin protein
      concentrations increased. Although mRNA for transferrin receptor decreased, mRNA
      for lactoferrin increased after incubation with the particle. Similar to changes
      in mRNA, transferrin concentration decreased, whereas that of lactoferrin
      increased. Deferoxamine, a metal chelator, inhibited these responses, and
      exposure of the cells to vanadium compounds alone reproduced elevations in
      lactoferrin mRNA. We conclude that increases in ferritin and lactoferrin
      expression can be metal dependent. This response can function to diminish the
      oxidative stress a metal chelate presents to a living system.

PMID- 9612289
TI  - In chyloptysis, SP-A affects the clearance of serum lipoproteins entering the
      airways.
AB  - Serum lipoproteins may enter the airways and appear in sputum (chyloptysis) when
      the lymphatic circulation is impaired by inflammation, neoplasia, or an abnormal
      proliferation of smooth muscle cells. While analyzing the bronchoalveolar lavage
      fluid of a patient with chyloptysis, we noticed that surfactant could not be
      separated from contaminating serum lipoproteins and speculated that lipoproteins
      might interact with surfactant components. To clarify this point we immobilized
      surfactant protein (SP) A on microtiter wells and incubated it with 125I-labeled
      very low density lipoproteins (VLDLs), low-density lipoproteins, and high-density
      lipoproteins. We found that SP-A binds lipoproteins. Studying in greater detail
      the interaction of SP-A with VLDLs, we found that the binding is time and
      concentration dependent; is inhibited by unlabeled lipoproteins, phospholipids,
      and antibodies to SP-A; is increased by Ca2+; and is unaffected by methyl alpha-D
      mannopyranoside. Whole surfactant is a potent inhibitor of binding. Furthermore,
      we found that SP-A increases the degradation of VLDLs by alveolar macrophages and
      favors the association of VLDLs with alveolar surfactant. We conclude that SP-A
      influences the disposal of serum lipoproteins entering the airways and speculate
      that binding to alveolar surfactant might represent an important step in the
      interaction between exogenous substances and the lung.

PMID- 9612290
TI  - Cloning and expression of rat lung acidic Ca(2+)-independent PLA2 and its organ
      distribution.
AB  - A clone for a rat acidic Ca(2+)-independent phospholipase A2 (aiPLA2) was
      isolated from a cDNA library prepared from rat granular pneumocytes with a probe
      based on the human aiPLA2 sequence (T.S. Kim, C.S. Sundaresh, S. I. Feinstein, C.
      Dodia, W. R. Skach, M. K. Jain, T. Nagase, N. Seki, K. Ishikawa, N. Nomura, and
      A. B. Fisher. J. Biol. Chem. 272: 2542-2550, 1997). In addition, a consensus
      sequence for mouse aiPLA2 was constructed from several mouse cDNA clones in the
      GenBank and dbEST databases. Each sequence codes for a 224-amino acid protein
      with 88% identity of the amino acids among the three species and conservation of
      a putative lipase motif (GDSWG). Translation of mRNA produced from the rat clone
      in a wheat germ system resulted in expression of PLA2 activity with properties
      similar to those of the human enzyme, i.e., acidic pH optimum and Ca2+
      independence. The localization of aiPLA2 in rat tissues was studied with the
      human cDNA probe, polyclonal and monoclonal antibodies, and aiPLA2 activity.
      aiPLA2 is present in the lung as evidenced by high levels of mRNA and protein
      expression and by enzymatic activity that is inhibited by anti-PLA2 antibody and
      by the transition state analog 1-hexadecyl-3-trifluoroethylglycero-sn-2
      phosphomethanol (MJ33). Immunocytochemistry showed the presence of aiPLA2 in
      alveolar type II cells, alveolar macrophages, and bronchiolar epithelium. In the
      brain, heart, liver, kidney, spleen, and intestine, aiPLA2 mRNA content was < 50%
      of that in the lung, immunoreactive protein was not detectable, and enzymatic
      activity was not inhibited by MJ33 or aiPLA2 antibody. These results show marked
      enrichment of aiPLA2 in the lung compared with the other organs and suggest
      translational control of aiPLA2 expression.

PMID- 9612291
TI  - Effect of anion secretion inhibitors on mucin content of airway submucosal gland
      ducts.
AB  - In porcine bronchi, inhibition of both Cl- and HCO3- transport is required to
      block the anion secretion response to ACh and to cause mucus accumulation within
      ACh-treated submucosal gland ducts [S. K. Inglis, M. R. Corboz, A. E. Taylor, and
      S. T. Ballard. Am. J. Physiol. 272 (Lung Cell. Mol. Physiol. 16): L372-L377,
      1997]. In this previous study, a combination of three potential HCO3- transport
      inhibitors [1 mM acetazolamide, 1 mM DIDS, and 0.1 mM dimethylamiloride (DMA)]
      was used to block carbonic anhydrase, Cl-/HCO3- exchange, and Na+/H+ exchange,
      respectively. The aim of the present study was to obtain a better understanding
      of the mechanism of ACh-induced HCO3- secretion in airway glands by determining
      which of the three inhibitors, in combination with bumetanide, is required to
      block anion secretion and so cause ductal mucin accumulation. Gland duct mucin
      content was measured in distal bronchi isolated from domestic pigs. Addition of
      either bumetanide alone, bumetanide plus acetazolamide, or bumetanide plus DIDS
      had no significant effect on ACh-induced mean gland duct mucin content. In
      contrast, glands treated with bumetanide plus DMA as well as glands treated with
      all four anion transport blockers were almost completely occluded with mucin
      after the addition of ACh. These data suggest that mucin is cleared from the
      ducts of bronchial submucosal glands by liquid generated from Cl(-)- and DMA
      sensitive HCO3- transport.

PMID- 9612292
TI  - Strain-associated differences in hypoxic chemosensitivity of the carotid body in
      rats.
AB  - Studies in humans indicate genetic effects on the ventilatory response to
      hypoxia, but the site of these effects is unknown. The present study explores the
      question of whether there are genetically directed effects on the intrinsic
      hypoxic chemosensitivity of the carotid body. The approach was to study these
      responses in two inbred rat strains [spontaneously hypertensive rats (SHR) and
      Fischer 344 (F-344)] and to measure in vivo carotid chemosensitivity as the
      change in carotid sinus nerve (CSN) activity during progressive, isocapnic
      hypoxia and the isolated, in vitro responses of excised superfused carotid
      bodies, loaded with the fluorimetric indicator fura 2, measured as the cytosolic
      calcium response to moderate hypoxia (PO2 = 55 mmHg). CSN responses in F-344 rats
      (n = 12) were uniformly low, with a shape parameter A of 13.8 +/- 6.59 (SE),
      whereas responses in SHR (n = 15) were sevenfold higher (108 +/- 24.1; P < 0.002)
      and showed greater variation. In vitro, intracellular calcium responses of
      superfused carotid bodies estimated from the fluorimetric ratio (340/380 nm)
      showed a greater peak increase during hypoxia in carotid bodies from SHR (140 +/-
      4.7%) than from F-344 rats (114 6.0%; P < 0.01). Our results indicate strain
      related differences in hypoxic chemosensitivity that are intrinsic to the carotid
      body and that could mediate genetic effects on ventilatory responsiveness to
      hypoxia.

PMID- 9612293
TI  - Myosin isoform shifts and decreased reactivity in hypoxia-induced hypertensive
      pulmonary arterial muscle.
AB  - The principal stimulus that evokes pulmonary hypertension is chronic alveolar
      hypoxia. Pulmonary hypertension is associated with remodeling of the vessel
      walls, involving hypertrophy and hyperplasia of pulmonary arterial smooth muscle
      (PASM) and a concomitant increase in the deposition of connective tissue,
      resulting in increased wall thickness. The purpose of the present study was to
      determine the effect of hypoxia-induced hypertension on the structure and
      function of PASM. Experiments were designed to determine whether hypoxia-induced
      pulmonary hypertension is associated with alterations in PASM: 1) reactivity to a
      variety of agonists, 2) contractile protein proportions and isoforms, and 3)
      structural properties. Young adult male rats were made hypoxic by lowering the
      fraction of inspired O2 (10%) for 14 days. Pulmonary arterial segments were
      isolated and dose-response curves to various agonists (high K+, norepinephrine,
      serotonin, angiotensin II, and adenosine) were generated. Gel electrophoresis was
      used to measure changes in the relative amounts of actin or myosin and of myosin
      heavy chain (MHC) isoforms. Structural changes were correlated with the
      pharmacological and biochemical data. Hypoxia-induced pulmonary hypertension
      caused a general decreased reactivity, an increase in the proportion of nonmuscle
      to muscle MHC isoforms in PASM, and an increase in arterial wall thickness with
      PASM hypertrophy or hyperplasia.

PMID- 9612294
TI  - Smooth muscle actin and myosin expression in cultured airway smooth muscle cells.
AB  - In this study, the expression of smooth muscle actin and myosin was examined in
      cultures of rat tracheal smooth muscle cells. Protein and mRNA analyses
      demonstrated that these cells express alpha- and gamma-smooth muscle actin and
      smooth muscle myosin and nonmuscle myosin-B heavy chains. The expression of the
      smooth muscle specific actin and myosin isoforms was regulated in the same
      direction when growth conditions were changed. Thus, at confluency in 1 or 10%
      serum-containing medium as well as for low-density cells (50-60% confluent)
      deprived of serum, the expression of the smooth muscle forms of actin and myosin
      was relatively high. Conversely, in rapidly proliferating cultures at low density
      in 10% serum, smooth muscle contractile protein expression was low. The
      expression of nonmuscle myosin-B mRNA and protein was more stable and was
      upregulated only to a small degree in growing cells. Our results provide new
      insight into the molecular basis of differentiation and contractile function in
      airway smooth muscle cells.

PMID- 9612295
TI  - Paraquat-induced phosphatidylserine oxidation and apoptosis are independent of
      activation of PLA2.
AB  - Paraquat is a pneumotoxin that causes lung injury by enhancing oxidative stress;
      however, the cellular responses to these redox events are undefined. We
      previously showed that paraquat produced selective peroxidation of
      phosphatidylserine that preceded apoptosis in 32D cells. We now report that the
      phospholipase A2 (PLA2) inhibitor quinacrine can attenuate phosphatidylserine
      oxidation and also block paraquat-induced apoptosis. Therefore, we investigated
      the potential for PLA2 to mediate apoptosis after paraquat. We found that, in
      contrast to quinacrine, the PLA2 inhibitors manoalide, aristolochic acid, and
      arachidonyl trifluoromethylketone failed to prevent paraquat-induced apoptosis.
      Moreover, no evidence of PLA2 activation was observed within 7 h after paraquat
      exposure. Finally, quinacrine failed to inhibit basal and 4-bromo-A-23187-induced
      release of [3H]arachidonic acid at concentrations that protected paraquat-induced
      apoptosis. We conclude that paraquat-induced phosphatidylserine oxidation and
      apoptosis occurred in the absence of PLA2 activation and that quinacrine
      protected phosphatidylserine and cell viability after paraquat in a PLA2
      independent manner.

PMID- 9612296
TI  - Carbachol-induced actin reorganization involves Gi activation of Rho in human
      airway smooth muscle cells.
AB  - To determine whether M2 muscarinic receptors are linked to the monomeric G
      protein Rho, we studied the effect of carbachol on actin reorganization (stress
      fiber formation) in cultured human airway smooth muscle cells that expressed
      mainly M2 muscarinic receptors by dual-fluorescence labeling of filamentous (F)
      and monomeric (G) actin. F-actin was labeled with FITC-labeled phalloidin, and G
      actin was labeled with Texas Red-labeled DNase I. Carbachol stimulation induced
      stress fiber formation (increased F-actin staining) in the cells and increased
      the F- to G-actin ratio 3.6 +/- 0.4-fold (mean +/- SE; n = 5 experiments).
      Preincubation with pertussis toxin, Clostridium C3 exoenzyme, or tyrosine kinase
      inhibitors reduced the carbachol-induced increase in stress fiber formation and
      significantly decreased the F- to G-actin ratio, whereas a mitogen-activated
      protein kinase inhibitor, a phosphatidylinositol 3-kinase inhibitor, and a
      protein kinase C inhibitor were without effect. This study demonstrates that in
      cultured human airway smooth muscle cells, muscarinic-receptor activation induces
      stress fiber formation via a pathway involving a pertussis-sensitive G protein,
      Rho proteins, and tyrosine phosphorylation.

PMID- 9612297
TI  - Pulmonary microvascular and macrovascular endothelial cells: differential
      regulation of Ca2+ and permeability.
AB  - Cytosolic Ca2+ concentration ([Ca2+]i) plays an important role in control of
      pulmonary vascular endothelial cell (ECs) barrier function. In this study, we
      investigated whether thapsigargin- and ionomycin-induced changes in cytosolic
      Ca2+ induce permeability in rat pulmonary microvascular (RPMV) versus
      macrovascular (RPA) ECs. In Transwell cultures, RPMVECs formed a tighter, more
      restrictive barrier than RPAECs to 12,000-, 72,000-, and 150,000-molecular-weight
      FITC-labeled dextrans. Thapsigargin (1 microM) produced higher [Ca2+]i levels in
      RPAECs than in RPMVECs and increased permeability in RPAEC but not in RPMVEC
      monolayers. Due to the attenuated [Ca2+]i response in RPMVECs, we investigated
      whether reduced activation of store-operated Ca2+ entry was responsible for the
      insensitivity to thapsigargin. Addition of the drug in media containing 100 nM
      extracellular Ca2+ followed by readdition media with 2 mM extracellular Ca2+
      increased RPMVEC [Ca2+]i to a level higher than that in RPAECs. Under these
      conditions, RPMVEC permeability was not increased, suggesting that [Ca2+]i in
      RPMVECs does not initiate barrier disruption. Also, ionomycin (1.4 microM) did
      not alter RPMVEC permeability, but the protein phosphatase inhibitor calyculin A
      (100 nM) induced permeability in RPMVECs. These data indicate that, whereas
      increased [Ca2+]i promotes permeability in RPAECs, it is not sufficient in
      RPMVECs, which show an apparent uncoupling of [Ca2+]i signaling pathways or
      dominant Ca(2+)-independent mechanisms from controlling cellular gap formation
      and permeability.

PMID- 9612298
TI  - Exogenous NO enhances hydrogen peroxide-mediated neutrophil adherence to cultured
      endothelial cells.
AB  - One important aspect of oxidant injury is the enhancement of neutrophil
      endothelial adhesion by oxidants such as hydrogen peroxide. Recent studies
      suggest that nitric oxide (NO) can limit oxidant-mediated tissue injury, since
      inhibitors of endogenous NO synthesis often promote neutrophil-endothelial
      adhesion. However, less is known about the direct role of exogenous NO in
      modulating proadhesive effects of oxidants. The objective of this study was to
      examine how an NO donor modifies hydrogen peroxide-mediated adhesion of
      neutrophils to cultured endothelial cells. Human umbilical vein endothelial cell
      monolayers were exposed for 30 min to 0-0.1 mM hydrogen peroxide with or without
      the NO donor spermine-NONOate (SNO; 0-0.5 mM), and the adhesion of 51Cr-labeled
      polymorphonuclear neutrophils (PMNs) was measured in a static adhesion assay. PMN
      adherence was not altered by either peroxide (up to 0.1 mM) or SNO (up to 0.5 mM)
      alone but was significantly increased by over 300% by coadministration of both
      0.1 mM peroxide and 0.5 mM SNO. This increase in adhesion with these two agents
      was correlated with an increase in the presentation of surface P-selectin but not
      intercellular adhesion molecule-1. Both PMN adhesion and P-selectin presentation
      were blocked by 0.1 mM desferrioxamine (an iron chelator) and 1 mM methionine (an
      oxyradical scavenger). WEB-2086, a platelet-activating factor-receptor antagonist
      (10 microM), also prevented PMN adhesion but not P-selectin expression. An
      antibody directed against either P-selectin or intercellular adhesion molecule-1
      also blocked adhesion. These data indicate that NO may actually exacerbate rather
      than protect against the inflammatory effects of peroxide in some models of
      inflammation through the synthesis of platelet-activating factor and the
      mobilization of P-selectin.

PMID- 9612299
TI  - Role of cAMP and neuronal K+ channels on alpha 2-AR-induced inhibition of ACh
      release in equine trachea.
AB  - To investigate the effects of changes in intracellular cAMP on alpha 2
      adrenoceptor (AR)-induced inhibition of airway acetylcholine (ACh) release, we
      examined the effects of the alpha 2-AR agonist clonidine on electrical field
      stimulation-evoked ACh release from equine tracheal parasympathetic nerves before
      and after treatment with 8-bromo-cAMP or forskolin. We also tested whether
      charybdotoxin (ChTX)- or iberiotoxin (IBTX)-sensitive Ca(2+)-activated K+
      channels mediate alpha 2-AR-induced inhibition by examining the effect of
      clonidine in the absence and presence of ChTX or IBTX on ACh release. The amount
      of released ACh was measured by HPLC coupled with electrochemical detection.
      Clonidine (10(-7) to 10(-5) M) dose dependently inhibited ACh release before and
      after treatment with 8-bromo-cAMP (10(-3) M) or forskolin (3 x 10(-5) M). ChTX
      and IBTX, both at the concentration of 5 x 10(-7) M, significantly increased ACh
      release; however, they did not alter the magnitude of clonidine-induced
      inhibition. These results indicated that in equine tracheal parasympathetic
      nerves, alpha 2-AR-induced inhibition of ACh release is via an intracellular cAMP
      independent pathway. Activation of both ChTX- and IBTX-sensitive Ca(2+)-activated
      K+ channels inhibits the electrical field stimulation-evoked ACh release, but
      these channels are not involved in the alpha 2-AR-induced inhibition of ACh
      release.

PMID- 9612300
TI  - Nitric oxide exposure inhibits endothelial NOS activity but not gene expression:
      a role for superoxide.
AB  - Recent studies have characterized a rebound pulmonary vasoconstriction with
      abrupt withdrawal of inhaled nitric oxide (NO) during therapy for pulmonary
      hypertension, suggesting that inhaled NO may downregulate basal NO production.
      However, the exact mechanism of this rebound pulmonary hypertension remains
      unclear. The objectives of these studies were to determine the effect of NO
      exposure on endothelial NO synthase (eNOS) gene expression, enzyme activity, and
      posttranslational modification in cultured pulmonary arterial endothelial cells.
      Sodium nitroprusside (SNP) treatment had no effect on eNOS mRNA or protein levels
      but did produce a significant decrease in enzyme activity. Furthermore, although
      SNP treatment induced protein kinase C (PKC)-dependent eNOS phosphorylation,
      blockade of PKC activity did not protect against the effects of SNP. When the
      xanthine oxidase inhibitor allopurinol or the superoxide scavenger 4,5-dihydroxy
      1-benzene-disulfonic acid were co-incubated with SNP, the inhibitory effects on
      eNOS activity could be partially alleviated. Also, the levels of superoxide were
      found to be elevated 4.5-fold when cultured pulmonary arterial endothelial cells
      were exposed to the NO donor spermine/NO. This suggests that NO can stimulate
      xanthine oxidase to cause an increase in cellular superoxide generation. A
      reaction between NO and superoxide would produce peroxynitrite, which could then
      react with the eNOS protein, resulting in enzyme inactivation. This mechanism may
      explain, at least in part, how NO produces NOS inhibition in vivo and may
      delineate, in part, the mechanism of rebound pulmonary hypertension after
      withdrawal of inhaled NO.

PMID- 9612301
TI  - Inhibition of voltage-gated K+ current in rat intrapulmonary arterial myocytes by
      endothelin-1.
AB  - Although endothelin (ET)-1 is an important regulator of pulmonary vascular tone,
      little is known about the mechanisms by which ET-1 causes contraction in this
      tissue. Using the whole cell patch-clamp technique in rat intrapulmonary arterial
      smooth muscle cells, we found that ET-1 and the voltage-dependent K+ (Kv)-channel
      antagonist 4-aminopyridine, but not the Ca(2+)-activated K(+)-channel antagonist
      charybdotoxin (ChTX), caused membrane depolarization. In the presence of 100 nM
      ChTX, ET-1 (10(-10) to 10(-7) M) caused a concentration-dependent inhibition of
      K+ current (56.2 +/- 3.8% at 10(-7) M) and increased the rate of current
      inactivation. These effects of ET-1 on K+ current were markedly reduced by
      inhibitors of protein kinase C (staurosporine and GF 109203X) and phospholipase C
      (U-73122) or under Ca(2+)-free conditions and were mimicked by activators of
      protein kinase C (phorbol 12-myristate 13-actetate and 1,2-dioctanoyl-sn
      glycerol). These data suggest that ET-1 modulated pulmonary vascular reactivity
      by depolarizing pulmonary arterial smooth muscle, due in part to the inhibition
      of Kv current that occurred via activation of the phospholipase C-protein kinase
      C signal transduction pathway.

PMID- 9612302
TI  - Thrombin regulation of endothelin-1 gene in isolated human pulmonary endothelial
      cells.
AB  - Endothelin (ET)-1 is a potent vasoconstrictor elicited from endothelial cells in
      response to a variety of stimuli and an important mediator for a variety of
      vascular diseases including pulmonary hypertension. In this paper, we describe
      the molecular regulation of the ET-1 gene in response to a vasoactive mediator,
      thrombin, in human pulmonary endothelial cells. Thrombin induces preproET-1 mRNA
      through a transcriptionally dependent mechanism, with a peak induction after 1 h
      of exposure. Analysis of chromatin structure identified several DNase I
      hypersensitive regions under both basal and thrombin-stimulated conditions that
      reside in the 5'-promoter region, indicating that the ET-1 promoter is a
      constitutive promoter. Deletion analysis was employed as a functional assay to
      identify regions of the ET-1 promoter that are important in transcriptional
      regulation. We found that sites between -141 and -378 bp are essential for basal
      activity and that those between -378 and -484 bp are essential for thrombin
      stimulated activity. However, full expression under both conditions required an
      element(s) within -952 bp.

PMID- 9612303
TI  - Interferon-gamma stimulates human Clara cell secretory protein production by
      human airway epithelial cells.
AB  - Clara cell secretory protein (CCSP) is an inhibitor of secretory phospholipase
      A2. It is produced by airway epithelial cells and is present in airway
      secretions. Because interferon (IFN)-gamma can induce gene expression in airway
      epithelial cells and may modulate the inflammatory response in the airway, it was
      of interest to study the effect of this cytokine on epithelial cell CCSP mRNA
      expression and CCSP protein synthesis. A human bronchial epithelial cell line
      (BEAS-2B) was used for this study. CCSP mRNA was detected by ribonuclease
      protection assay. IFN-gamma was found to increase CCSP mRNA expression in a time-
      and dose-dependent manner. The CCSP mRNA level increased after IFN-gamma (300
      U/ml) treatment for 8-36 h, with the peak increase at 18 h. Immunobloting of CCSP
      protein also demonstrated that IFN-gamma induced the synthesis and secretion of
      CCSP protein in a time-dependent manner. Nuclear run-on, CCSP reporter gene
      activity assay, and CCSP mRNA half-life assay demonstrated that IFN-gamma-induced
      increases in CCSP gene expression were mediated, at least in part, at the
      posttranscriptional level. The present study demonstrates that IFN-gamma can
      induce increases in steady-state mRNA levels and protein synthesis of human CCSP
      protein in airway epithelial cells and may modulate airway inflammatory responses
      in this manner.

PMID- 9612318
TI  - One hundred years of journal publication.

PMID- 9612319
TI  - Renal potassium transport: mechanisms and regulation.
AB  - The regulation of potassium metabolism involves mechanisms for the appropriate
      distribution between the intra- and extracellular fluid compartments and for the
      excretion by the kidney. Clearance and single nephron studies show that renal
      excretion is determined by regulated potassium secretion and potassium
      reabsorption, respectively, in principal and intercalated cells of the distal
      nephron. Measurement of the electrochemical driving forces acting on potassium
      transport across individual cell membranes and characterization of several
      ATPases and potassium channels provide insights into the transport and regulation
      of renal potassium excretion.

PMID- 9612320
TI  - Dose-dependent effects of CRF-like diuretic peptide on transcellular and
      paracellular transport pathways.
AB  - The mechanism of action of synthetic Culex corticotropin-releasing factor (CRF)
      like diuretic peptide (CCRF-DP) was investigated in isolated, perfused Malpighian
      tubules of the yellow fever mosquito, Aedes aegypti. Low concentrations of CCRF
      DP (10(-10) and 10(-9) M) caused depolarizing oscillations of the lumen-positive
      transepithelial voltage (Vt) in Malpighian tubules, whereas high concentrations
      (10(-8) and 10(-7) M) first depolarized and then transiently hyperpolarized Vt;
      CCRF-DP always lowered transepithelial resistance (Rt), regardless of voltage
      depolarization or hyperpolarization. The short-circuit current (Isc), an
      electrical estimate of active transepithelial transport of Na and K, remained
      unchanged at low concentrations of CCRF-DP, but Isc more than doubled at high
      concentrations. These effects of CCRF-DP suggest dose-dependent sites of action:
      low concentrations of CCRF-DP affect the paracellular pathway, and high
      concentrations affect both paracellular and transcellular pathways.

PMID- 9612321
TI  - A mathematical model of the inner medullary collecting duct of the rat: pathways
      for Na and K transport.
AB  - A mathematical model of the inner medullary collecting duct (IMCD) of the rat has
      been developed representing Na+, K+, Cl-, HCO3-, CO2, H2CO3, phosphate, ammonia,
      and urea. Novel model features include: finite rates of hydration of CO2, a
      kinetic representation of the H-K-ATPase within the luminal cell membrane,
      cellular osmolytes that are regulated in defense of cell volume, and the repeated
      coalescing of IMCD tubule segments to yield the ducts of Bellini. Model transport
      is such that when entering Na+ is 4% of filtered Na+, approximately 75% of this
      load is reabsorbed. This requirement renders the area-specific transport rate for
      Na+ comparable to that for proximal tubule. With respect to the luminal membrane,
      there is experimental evidence for both NaCl cotransport and an Na+ channel in
      parallel. The experimental constraints that transepithelial potential difference
      is small and that the fractional apical resistance is greater than 85% mandate
      that more than 75% of luminal Na+ entry be electrically silent. When Na+ delivery
      is limited, an NaCl cotransporter can be effective at reducing luminal Na+
      concentration to the observed low urinary values. Given the rate of transcellular
      Na+ reabsorption, there is necessarily a high rate of peritubular K+ recycling;
      also, given the lower bound on luminal membrane Cl- reabsorption, substantial
      peritubular Cl- flux must be present. Thus, if realistic limits on cell membrane
      electrical resistance are observed, then this model predicts a requirement for
      peritubular electroneutral KCl exit.

PMID- 9612322
TI  - A mathematical model of the inner medullary collecting duct of the rat: acid/base
      transport.
AB  - A mathematical model of the inner medullary collecting duct (IMCD) of the rat has
      been developed that is suitable for simulating luminal buffer titration and
      ammonia secretion by this nephron segment. Luminal proton secretion has been
      assigned to an H-K-ATPase, which has been represented by adapting the kinetic
      model of the gastric enzyme by Brzezinski et al. (P. Brzezinski, B. G. Malmstrom,
      P. Lorentzon, and B. Wallmark. Biochim. Biophys. Acta 942: 215-219, 1988). In
      shifting to a 2 H+:1 ATP stoichiometry, the model enzyme can acidify the tubule
      lumen approximately 3 pH units below that of the cytosol, when luminal K+ is in
      abundance. Peritubular base exit is a combination of ammonia recycling and HCO3-
      flux (either via Cl-/HCO3- exchange or via a Cl- channel). Ammonia recycling
      involves NH4(+) uptake on the Na-K-ATPase followed by diffusive NH3 exit [S. M.
      Wall. Am. J. Physiol. 270 (Renal Physiol. 39): F432-F439, 1996]; model
      calculations suggest that this is the principal mode of base exit. By virtue of
      this mechanism, the model also suggests that realistic elevations in peritubular
      K+ concentration will compromise IMCD acid secretion. Although ammonia recycling
      is insensitive to carbonic anhydrase (CA) inhibition, the base exit linked to
      HCO3- flux provides a CA-sensitive component to acid secretion. In model
      simulations, it is observed that increased luminal NaCl entry increases ammonia
      cycling but decreases peritubular Cl-/HCO3- exchange (due to increased cell Cl-).
      This parallel system of peritubular base exit stabilizes acid secretion in the
      face of variable Na+ reabsorption.

PMID- 9612323
TI  - Volume repletion after exercise-induced volume depletion in humans: replacement
      of water and sodium losses.
AB  - Sodium and water loss during, and replacement after, exercise-induced volume
      depletion was investigated in six volunteers volume depleted by 1.89 +/- 0.17%
      (SD) of body mass by intermittent exercise in a warm, humid environment. Subjects
      exercised in a large, open plastic bag, allowing collection of all sweat secreted
      during exercise. For over 60 min beginning 40 min after the end of exercise,
      subjects ingested drinks containing 0, 25, 50, or 100 mmol/l sodium (trials 0,
      25, 50, and 100) in a volume (ml) equivalent to 150% of the mass lost (g) by
      volume depletion. Body mass loss and sweat electrolyte (Na+, K+, and Cl-) loss
      were the same on each trial. The measured sweat sodium concentration was 49.2 +/-
      18.5 mmol/l, and the total loss (63.9 +/- 38.7 mmol) was greater than that
      ingested on trials 0 and 25. Urine production over the 6-h recovery period was
      inversely related to the amount of sodium ingested. Subjects were in whole body
      negative sodium balance on trials 0 (-104 +/- 48 mmol) and 25 (-65 +/- 30 mmol)
      and essentially in balance on trial 50 (-13 +/- 29 mmol) but were in positive
      sodium balance on trial 100 (75 +/- 40 mmol). Only on trial 100 were subjects in
      positive fluid balance at the end of the study. There was a large urinary loss of
      potassium over the recovery period on trial 100, despite a negligible intake
      during volume repletion. These results confirm the importance of replacement of
      sodium as well as water for volume repletion after sweat loss. The sodium intake
      on trial 100 was appropriate for acute fluid balance restoration, but its
      consequences for potassium levels must be considered to be undesirable in terms
      of whole body electrolyte homeostasis for anything other than the short term.

PMID- 9612324
TI  - Renoprotective effects of nitric oxide in angiotensin II-induced hypertension in
      the rat.
AB  - Experiments were performed in anesthetized male Sprague-Dawley rats to determine
      whether increased nitric oxide (NO) activity during the development of
      hypertension exerts a protective effect on renal cortical blood flow (CBF) and
      medullary blood flow (MBF). The effects of acute NO synthase inhibition on renal
      function and on CBF and MBF, measured by laser-Doppler flow probes, were
      evaluated in control and ANG II-infused hypertensive rats, prepared by the
      infusion of ANG II at a rate of 65 ng/min via osmotic minipumps implanted
      subcutaneously for 13 days. In normotensive rats (n = 8), intravenous infusion of
      N omega-nitro-L-arginine (NLA; 20 micrograms.100 g-1.min-1) decreased CBF by 21
      +/- 4% and MBF by 49 +/- 8% and increased blood pressure from 118 +/- 1 to 140 +/
      2 mmHg. In ANG II-infused rats (n = 7), CBF and MBF decreased by 46 +/- 5% and
      25 +/- 6%, respectively, during infusion of NLA. Arterial pressure increased from
      160 +/- 5 to 197 +/- 7 mmHg, which was a greater absolute increase than in
      normotensive controls. Basal renal blood flow (RBF), estimated from p
      aminohippurate clearance and hematocrit, was similar in both the control (6.0 +/-
      0.5 ml.min-1.g-1) and hypertensive (6.0 +/- 0.6 ml.min-1.g-1) rats. However, NLA
      induced reductions in RBF averaged 60 +/- 5% in the hypertensive rats, compared
      with 31 +/- 9% observed in control rats. GFR in control (0.97 +/- 0.03 ml.min-1.g
      1) and hypertensive rats (0.78 +/- 0.12 ml.min-1.g-1) decreased to a similar
      extent during the first 30-min period of NLA infusion. GFR returned toward
      control levels in control rats; in contrast, GFR remained significantly decreased
      in the ANG II-infused rats (0.58 +/- 0.11 ml.min-1.g-1). Basal urinary sodium
      excretion (0.2 +/- 0.08 mueq.min-1.g-1), fractional excretion of sodium (0.3 +/-
      0.13%), and urine flow (4.9 +/- 0.39 microliters.min-1.g-1) in hypertensive rats
      did not increase significantly after NLA treatment as occurred in normotensive
      controls. These data suggest that a compensatory increase in nitric oxide
      activity partially counteracts the vasoconstrictor influence of elevated ANG II
      levels to regulate renal hemodynamics and maintain cortical perfusion in the
      renal circulation.

PMID- 9612325
TI  - Maturation of rabbit proximal straight tubule chloride/base exchange.
AB  - The present in vitro microperfusion study compared the mechanism and rates of
      NaCl transport in neonatal and adult rabbit proximal straight tubules. In
      proximal straight tubules perfused with a late proximal tubular fluid and bathed
      in a serumlike albumin solution, the rate of volume absorption (JV) was 0.54 +/-
      0.10 and 0.12 +/- 0.05 nl.mm-1.min-1 in adults and neonates, respectively (P <
      0.05). With the addition of 10(-5) M bath ouabain, JV decreased to 0.27 +/- 0.07
      and -0.03 +/- 0.04 nl.mm-1.min-1 in adult and neonatal tubules, respectively (P <
      0.05), consistent with lower rates of active and passive NaCl transport in the
      neonatal proximal straight tubule. The effect of luminal sodium and chloride
      removal on intracellular pH was used to assess the relative rates of Na+/H+ and
      Cl-/base exchange. The rates of Na+/H+ and Cl-/base exchange were approximately
      fivefold less in neonatal proximal straight tubules than adult tubules. In both
      neonatal and adult proximal straight tubules, the rate of Cl-/base exchange was
      not affected by formate, bicarbonate, or cyanide and acetazolamide, consistent
      with Cl-/OH- exchange. These data demonstrate an increase in proximal straight
      tubule NaCl transport during postnatal renal development.

PMID- 9612326
TI  - Assessment of the charge selectivity of glomerular basement membrane using Ficoll
      sulfate.
AB  - The extent to which the glomerular basement membrane (GBM) contributes to the
      charge selectivity of the glomerular capillary wall has been controversial. To
      reexamine this issue, the size and charge selectivity of filters made from
      isolated rat GBM were assessed, using polydisperse Ficoll and Ficoll sulfate as
      test macromolecules. Ficoll sulfate, a novel tracer with spherical shape
      synthesized for this purpose, exhibited little or no binding to serum albumin,
      thereby avoiding a major difficulty that has been reported with dextran sulfate.
      The sieving coefficients of Ficoll sulfate were not different from those of
      Ficoll at physiological ionic strength, although the values for Ficoll sulfate
      were depressed at low ionic strength. These results confirm that the GBM
      possesses fixed negative charges but suggest that its charge density is
      insufficient to confer significant charge selectivity under physiological
      conditions, where electrostatic interactions are relatively well screened. The
      sieving coefficients of Ficoll sulfate and Ficoll were elevated significantly and
      by similar amounts when bovine serum albumin (BSA) was present in the retentate
      at 4 g/dl. This could be explained as the combined effect of two nonspecific
      physical factors, namely, the reduction in filtration velocity due to the osmotic
      pressure of BSA and the effect on macromolecular partitioning of repulsive solute
      solute interactions. The view that BSA does not affect the intrinsic properties
      of the GBM is supported also by the absence of an effect on the hydraulic
      permeability of isolated GBM. The sieving coefficient of BSA was roughly half
      that of Ficoll or Ficoll sulfate of similar Stokes-Einstein radius. Given the
      finding of negligible charge selectivity, this difference may be attributed to
      the nonspherical shape of albumin. The results suggest that, to the extent that
      isolated GBM is similar to GBM in vivo, the charge selectivity of the glomerular
      capillary wall must be due to the endothelial and/or epithelial cell layers.

PMID- 9612327
TI  - Angiotensin (AT1A) receptor-mediated increases in transcellular sodium transport
      in proximal tubule cells.
AB  - Angiotensin II (ANG II), acting through angiotensin type 1A receptors (AT1A), is
      important in regulating proximal tubule salt and water balance. AT1A are present
      on apical (AP) and basolateral (BL) surfaces of proximal tubule epithelial cells
      (PTEC). The molecular mechanism of AT1A function in epithelial tissue is not well
      understood, because specific binding of ANG II to intact PTEC has not been found
      and because a number of isoforms of AT receptors are present in vivo. To overcome
      this problem, we developed a cell line from opossum kidney (OK) proximal tubule
      cells, which stably express AT1A (Kd = 5.27 nM, Bmax = 6.02 pmol/mg protein).
      Characterization of nontransfected OK cells revealed no evidence of AT1A mRNA
      (reverse transcriptase-polymerase chain reaction analysis) or protein (125I
      labeled ANG II binding studies) expression. In cells stably expressing AT1A, ANG
      II binding was saturable, reversible, and regulated by G proteins. Transfected
      receptors were coupled to increases in intracellular calcium and inhibition of
      cAMP. To determine the polarity of AT1A expression and function in proximal
      tubules, transfected cells were grown to confluence on membrane inserts under
      conditions that allowed selective access to AP or BL surfaces. AT1A were
      expressed on both AP (Kd = 8.7 nM, Bmax = 3.33 pmol/mg protein) and BL (Kd = 10.1
      nM, Bmax = 5.50 pmol/mg protein) surfaces. Both AP and BL AT1A receptors
      underwent agonist-dependent endocytosis (AP receptor: t1/2 = 7.9 min, Ymax =
      78.5%; BL receptor: t1/2 = 2.1 min, Ymax = 86.3%). In cells transfected with
      AT1A, ANG II caused time- and concentration-dependent increases in
      transepithelial 22Na transport (2-fold over control at 20 min) by increasing Na/H
      exchange. In conclusion, we have established a stable proximal tubule cell line
      that expresses AT1A on both AP and BL surfaces, undergoes agonist-dependent
      receptor endocytosis, and is functional, as evidenced by inhibition of cAMP and
      increases in cytosolic calcium mobilization and transepithelial sodium movement.
      This cell line should prove useful for understanding the molecular and
      biochemical regulation of AT1A expression and function in PTEC.

PMID- 9612328
TI  - Regional time-dependent changes in vasopressin V2 receptor expression in the rat
      kidney during water restriction.
AB  - Elevations of arginine vasopressin (AVP) binding to renal vasopressin V2
      receptors (V2R) enhance water and urea reabsorption in the collecting duct
      epithelium. This study was designed to quantify the levels of V2R mRNA and
      protein within the distinct regions of the Sprague-Dawley rat kidney (i.e., the
      cortex and outer and inner medulla) during 24 and 48 h of water restriction. A
      competitive reverse transcription-polymerase chain reaction (RT-PCR) assay was
      developed to quantify changes in the V2R mRNA, in which a deletion mutant RNA
      transcript was used to control for the efficiency of RT-PCR. Western blot
      analysis was utilized for the quantification of the V2R protein. The results
      showed that the steady-state levels of the V2R mRNA decreased in a time-dependent
      manner in the cortex and outer and inner medulla throughout 48 h of water
      restriction. Western blot analysis revealed that the V2R protein in the renal
      cortex decreased after the initial 24 h of water restriction and remained
      decreased at 48 h. In contrast, outer medullary V2R protein decreased
      significantly only after 48 h of water restriction, whereas no significant change
      in the inner medullary V2R protein was observed throughout the 48 h of water
      restriction. These results suggest that water restriction leads to a regional
      time-dependent downregulation of the V2R mRNA and protein within the rat kidney.
      The stability of the plasma membrane V2R protein within the inner medulla may
      allow for the optimization of urine concentration and minimize water loss during
      periods of water restriction.

PMID- 9612329
TI  - Dietary sodium affects systemic and renal hemodynamic response to NO inhibition
      in healthy humans.
AB  - Animal studies have indicated that increased nitric oxide (NO) synthesis plays a
      significant role in the renal adaptation to increased sodium intake. To
      investigate the role of NO during increased sodium intake in humans, we studied
      the effect of acute, systemic injection of NG-monomethyl-L-arginine (L-NMMA) on
      renal hemodynamics [glomerular filtration rate and renal plasma flow (GFR and
      RPF, respectively)], urinary sodium excretion (FENa), systemic hemodynamics [mean
      arterial blood pressure and heart rate (MAP and HR)], and plasma levels of
      several vasoactive hormones in 12 healthy subjects during high (250 mmol/day) and
      low (77 mmol/day) sodium intake in a crossover design. The sodium diets were
      administered for 5 days before the L-NMMA treatments, in randomized order, with a
      washout period of 9 days between each diet and L-NMMA treatment. GFR and RPF were
      measured using the renal clearance of 51Cr-labeled EDTA and 125I-labeled hippuran
      by the constant infusion technique in clearance periods of 30-min duration. Two
      baseline periods were obtained, after which L-NMMA was given (3 mg/kg over 10
      min), and the effect of treatment was followed over the next five clearance
      periods. During high sodium intake, L-NMMA induced a more pronounced relative
      decrease in RPF (P = 0.0417, ANOVA), a more pronounced relative decrease in FENa
      (P = 0.0032, ANOVA), and a more pronounced relative increase in MAP (P = 0.0231,
      ANOVA). During low sodium intake, the effect of L-NMMA on FENa was abolished.
      During low sodium intake, L-NMMA induced a sustained drop in plasma renin (31 +/-
      5 vs. 25 +/- 5 microU/ml, P < 0.001), which was not seen during high sodium
      intake. The data indicate that increased production of NO is an important part of
      the adaptation to increased dietary sodium intake in healthy humans, with respect
      to renal hemodynamics, sodium excretion, and the secretion of renin.

PMID- 9612330
TI  - Heterogeneity of glutathione synthesis and secretion in the proximal tubule of
      the rabbit.
AB  - This study was designed to examine the synthesis and possible secretion of
      glutathione (GSH) in the S1, S2, and S3 segments of the rabbit proximal tubule.
      GSH synthesis and secretion rates were measured in the three segments of the
      proximal tubule, using the isolated perfused renal tubule technique. Tritiated
      (3H) glycine was perfused into segments and synthesized [3H]GSH (3H on the
      glycine residue) was measured in the bathing solution, collectate, and tubule
      extract. In the S1 segments, GSH was synthesized at the rate of 8.65 +/- 0.88
      fmol.min-1.mm-1 tubule length and preferentially secreted into the lumen at the
      rate of 7.28 +/- 0.74 fmol.min-1.mm-1. The difference between synthesis and
      secretion appeared in the bathing solution. The S2 segment synthesized GSH at the
      rate of 3.88 +/- 0.82 and secreted GSH at the rate of 2.78 +/- 0.57 fmol.min-1.mm
      1. GSH synthesis and secretion rates in the S3 segment were 5.45 +/- 1.19 and
      4.22 +/- 1.16 fmol.min-1.mm-1, respectively. Cellular concentrations of [3H]GSH
      increased along the length of the proximal tubule, with the highest
      concentrations in the S3 segment. The respective GSH cellular concentrations in
      the S1, S2, and S3 segments were 35.89 +/- 10.51, 49.65 +/- 9.32, and 116.90 +/-
      15.76 microM. These findings indicate that there is heterogeneity of GSH
      synthesis along the proximal tubule and that synthesized GSH is secreted
      preferentially into the lumen.

PMID- 9612331
TI  - Developmental expression of human angiotensinogen in transgenic mice.
AB  - Transgenic mice containing the human angiotensinogen (HAGT) gene were utilized to
      determine the developmental regulation of HAGT expression. RNase protection assay
      on total RNA obtained from whole transgenic fetuses revealed that HAGT expression
      was first detected at embryonic day 8.5 (E8.5) and was abundant from E9.5 onward.
      The earliest expression of the HAGT transgene appeared to precede the earliest
      expression of the endogenous mouse AGT gene by 1-2 days. Northern blot analysis
      revealed moderate levels of HAGT mRNA in liver and kidney and low levels of HAGT
      mRNA in heart and brain from E16.5 (day 16.5 of gestation) onward. HAGT mRNA in
      liver, although abundant during late gestation and in 2-wk-old and adult mice,
      decreased transiently around birth. In situ hybridization performed on sections
      from whole fetuses revealed that HAGT mRNA was restricted to the developing liver
      and heart between E9.5 and E11.5 but became more widespread to include the
      developing aorta, brain, subcutaneous tissues, and vertebra at E13.5. In situ
      hybridization analysis on fetal kidneys from late gestation, newborn, and 2-wk
      old mice demonstrated a progressive restriction of HAGT mRNA to developing
      cortical proximal tubular cells. These data illustrate the developmental tissue
      specific regulation of HAGT expression and demonstrate that sequences present in
      the transgene can confer an appropriate developmental expression profile.

PMID- 9612332
TI  - Effects of acute AT1 receptor blockade by candesartan on arterial pressure and
      renal function in rats.
AB  - Experiments were performed on normal anesthetized rats to determine the effects
      of candesartan, a novel AT1 receptor antagonist, on the arterial pressure and
      renal hemodynamic responses to bolus doses of angiotensin II (ANG II) and on
      renal hemodynamics and sodium excretion. Control arterial pressure responses to
      bolus ANG II doses of 10, 50, 100 and 1,000 ng were 26 +/- 6, 54 +/- 7, 57 +/- 7,
      and 79 +/- 7 mmHg; the decreases in cortical renal blood flow (CRBF), measured
      with laser-Doppler flowmetry, were 47 +/- 9, 64 +/- 8, 71 +/- 6, and 82 +/- 6%.
      The vasoconstrictor responses to ANG II up to 1,000 ng were completely blocked by
      candesartan doses of 1 and 0.1 mg/kg, whereas treatment with 0.01 mg/kg
      candesartan attenuated the arterial pressure and CRBF responses. The higher doses
      of candesartan (1 and 0.1 mg/kg) elicited rapid decreases in arterial pressure,
      leading to associated decreases in sodium excretion. Renal blood flow (RBF),
      glomerular filtration rate (GFR), and urine flow also decreased following
      treatment with candesartan at 1 mg/kg. In contrast, when candesartan was given at
      0.01 mg/kg, which did not decrease arterial pressure significantly, there were
      significant increases in GFR (16 +/- 4), RBF (9 +/- 2), urine flow (11 +/- 2),
      sodium excretion (35 +/- 7), and fractional sodium excretion (39 +/- 8%). The
      inability to overcome blockade, even with very high ANG II doses, indicates that
      candesartan is a potent noncompetitive blocker of ANG II pressor and renal
      vasoconstrictor effects. The lower candesartan dose that did not cause
      significant hypotension elicited substantial increases in RBF, GFR, and sodium
      excretion, revealing the direct renal vasodilator and natriuretic effects of AT1
      receptor blockade.

PMID- 9612333
TI  - Nitric oxide increases the activity of the apical 70-pS K+ channel in TAL of rat
      kidney.
AB  - We have previously shown that nitric oxide (NO) mediates the stimulatory effect
      of angiotensin II on the apical 70-pS K+ channel in the thick ascending limb
      (TAL) of Henle's loop of the rat kidney (12). In the present study, we used the
      patch-clamp technique to examine the effects of NO on the 70-pS K+ channel.
      Addition of 10 microM S-nitroso-N-acetylpenicillamine (SNAP), a NO donor,
      increased the channel activity in cell-attached patches. In contrast, application
      of 100 microM N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of
      nitric oxide synthase (NOS), reduced the channel activity by 75 +/- 7%. The
      effect of L-NAME was the result of inhibiting NOS, since D-NAME, which does not
      block NOS activity, had no effect on the channel activity. In addition, the
      effect of L-NAME was abolished in the presence of 1 mM L-arginine or by addition
      of 10 microM SNAP, further supporting the role of NO. Finally, the L-NAME-induced
      inhibition was also reversed by adding 8-bromoguanosine 3',5'-cyclic
      monophosphate (8-BrcGMP). That the effect of NO is mediated by the cGMP-dependent
      pathway is also suggested by experiments in which inhibition of guanylate cyclase
      abolished the effect of SNAP. Finally, 10 microM SNAP significantly increased
      cGMP concentration of the medullary TAL from 12.4 fM/microgram protein to 38.9
      fM/microgram protein, as measured with ELISA. We conclude that NO is involved in
      regulating the activity of the apical 70-pS K+ channel in the TAL of the rat
      kidney.

PMID- 9612334
TI  - Single cell RT-PCR analysis of ClC-2 mRNA expression in ureteric bud tip.
AB  - Embryonic epithelia at the tip of the ureteric bud (UB) face the interspace
      between epithelial and mesenchymal cells and are fundamentally involved in
      reciprocal signaling during early nephrogenesis. To characterize their membrane
      conductive proteins, patch-clamp and single cell RT-PCR techniques were applied
      to embryonic rat UBs [embryonic day 17 (day E17)] microdissected from the outer
      cortex. Cells at the UB tip had a high whole cell conductance (14 +/- 2 nS/10 pF,
      n = 8). The main fractional conductance resembled that of Ca-activated Cl
      channels in nonepithelial cells, with its time-dependent activation at
      depolarizing and inactivation at hyperpolarizing voltages. A second Cl-selective
      current fraction, by contrast, activated slowly during strong hyperpolarization,
      suggestive of a ClC-2-mediated conductance. To determine the origin of this
      current, cytoplasm was harvested into the patch pipette, RNA was reverse
      transcribed, and cDNA encoding the glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH) housekeeper gene or the ClC-2 Cl channel was amplified by polymerase
      chain reaction (PCR). GAPDH and ClC-2 PCR products were identified in 23 and 8
      (out of a total of 57) single cell cDNA samples, respectively. ClC-2 PCR products
      with two different lengths were obtained, which might be due to two alternatively
      spliced ClC-2 mRNA isoforms. This first and combined approach by patch-clamp and
      single cell RT-PCR techniques to embryonic epithelia indicates that 1) cells at
      the UB tip express a phenotype remarkably different from that of postembryonic
      collecting duct principal cells and that 2) ClC-2 is likely to have a key role in
      early nephrogenesis.

PMID- 9612335
TI  - Increased calcium oxalate monohydrate crystal binding to injured renal tubular
      epithelial cells in culture.
AB  - The retention of crystals in the kidney is considered to be a crucial step in the
      development of a renal stone. This study demonstrates the time-dependent
      alterations in the extent of calcium oxalate (CaOx) monohydrate (COM) crystal
      binding to Madin-Darby canine kidney (MDCK) cells during their growth to
      confluence and during the healing of wounds made in confluent monolayers. As
      determined by radiolabeled COM crystal binding studies and confirmed by confocal
      scanning laser microscopy, relatively large amounts of crystals (10.4 +/- 0.4
      micrograms/cm2) bound to subconfluent cultures that still exhibited a low
      transepithelial electrical resistance (TER < 400 omega.cm2). The development of
      junctional integrity, indicated by a high resistance (TER > 1,500 omega.cm2), was
      followed by a decrease of the crystal binding capacity to almost undetectable low
      levels (0.13 +/- 0.03 microgram/cm2). Epithelial injury resulted in increased
      crystal adherence. The highest level of crystal binding was observed 2 days
      postinjury when the wounds were already morphologically closed but TER was still
      low. Confocal images showed that during the repair process, crystals selectively
      adhered to migrating cells at the wound border and to stacked cells at sites were
      the wounds were closed. After the barrier integrity was restored, crystal binding
      decreased again to the same low levels as in undamaged controls. These results
      indicate that, whereas functional MDCK monolayers are largely protected against
      COM crystal adherence, epithelial injury and the subsequent process of wound
      healing lead to increased crystal binding.

PMID- 9612336
TI  - Regulation of the polymeric immunoglobulin receptor by water intake and
      vasopressin in the rat kidney.
AB  - The polymeric immunoglobulin receptor (pIgR) transports polymeric immunoglobulins
      (IgA) from the basolateral to the apical surface of epithelial cells. At the
      apical surface, its amino-terminal domain, termed secretory component (SC), is
      proteolytically cleaved and released either unbound (free SC) or bound to IgA. We
      examined the effects of changes in water balance and vasopressin on the
      production and secretion of the pIgR in the rat kidney in vivo. Water deprivation
      induced a 2.7-fold increase in the pIgR mRNA and a 2.2-fold increase in
      intracellular pIgR protein compared with water-loaded animals. Physiological
      doses of desmopressin reproduced the effects of water deprivation on mRNA and
      intracellular protein levels, suggesting that pIgR expression may be regulated by
      a vasopressin-coupled mechanism. Secretion of free SC and secretory IgA in the
      urine, however, correlated directly with water intake and urine flow. These
      results suggest that hydration status and vasopressin may affect the mucosal
      immunity of the kidney by regulating at different steps the epithelial cell
      production and secretion of the polymeric immunoglobulin transporter/ secretory
      component.

PMID- 9612337
TI  - Vasopressin-elicited water and urea permeabilities are altered in IMCD in
      hypercalcemic rats.
AB  - To investigate how hypercalcemia blunts renal concentrating ability, alterations
      in basal and arginine vasopressin (AVP)-elicited osmotic water (Pf) and urea
      (Purea) permeabilities were measured in isolated perfused terminal inner
      medullary collecting ducts (IMCD) from control and chronically hypercalcemic rats
      after dihydrotachysterol (DHT) (M. Levi, L. Peterson, and T. Berl. Kidney Int.
      23: 489-497, 1983) treatment. The IMCD Pf of DHT-treated rats did not increase
      significantly after AVP and was accompanied by a significant 87 +/- 4% reduction
      in aquaporin-2 (AQP-2) protein but not mRNA. In contrast, both basal and AVP
      elicited IMCD Purea from DHT rats were significantly increased and accompanied by
      a significant 41 +/- 11% increase in AVP-regulated urea transporter protein
      content. Immunoblotting with anti-calcium/polyvalent cation-sensing receptor
      protein (CaR) antiserum revealed specific alterations in CaR bands in endosomes
      purified from the apical membranes of inner medulla of DHT rats. These data are
      the first detailed analyses of hypercalcemia-induced alterations in AVP-regulated
      permeabilities and membrane transporters in IMCD. We conclude that selective
      alterations in IMCD transport occur in hypercalcemia, permitting the body to
      dispose of excess calcium without forming calcium-containing renal stones.

PMID- 9612338
TI  - Monoclonal antibody P-31 recognizes a novel intermediate filament-associated
      protein (p250) in rat podocytes.
AB  - The visceral glomerular epithelial cells (GECs) or podocytes of the renal
      glomerulus constitute a highly specialized epithelium. To study the nature of
      podocytes, we established mouse monoclonal antibodies against GEC. Clone P-31
      reacted exclusively with the cytoplasm of GEC by immunofluorescence. Immunoblot
      analysis with P-31 showed that a single band of 250 kDa was detectable in a
      glomerular lysate. The 250-kDa polypeptide (p250) was recovered from Triton X-100
      insoluble fractions of isolated glomeruli, suggesting that this molecule is
      associated with the cytoskeleton. Immunogold staining with P-31 demonstrated that
      the gold particles were located at the intersections of vimentin-type
      intermediate filaments of podocytes. In developing kidney, this protein first
      appeared in immature GECs during the S-shaped body stage. In puromycin
      aminonucleoside nephrosis, p250 was dramatically increased in glomeruli where
      enhanced desmin expression was observed in GECs. These results indicate that p250
      is a novel intermediate filament-associated protein and plays a role in the
      organization of the intermediate filament network in both normal and diseased
      conditions.

PMID- 9612345
TI  - Effects of a chronic high-salt diet on large artery structure: role of endogenous
      bradykinin.
AB  - Bradykinin activity could explain the blood pressure increase during NaCl loading
      in hypertensive animals, but its contribution on vascular structure was not
      evaluated. We determined cardiac mass and large artery structure after a chronic,
      4-mo, high-salt diet in combination with bradykinin B2-receptor blockade by Hoe
      140. Four-week-old rats were divided into eight groups according to strain
      [spontaneously hypertensive rats (SHR) vs. Wistar-Kyoto (WKY) rats], diet (0.4
      vs. 7% NaCl), and treatment (Hoe-140 vs. placebo). In WKY rats, a high-salt diet
      significantly increased intra-arterial blood pressure with minor changes in
      arterial structure independently of Hoe-140. In SHR, blood pressure remained
      stable but 1) the high-salt diet was significantly associated with cardiovascular
      hypertrophy and increased arterial elastin and collagen, and 2) Hoe-140 alone
      induced carotid hypertrophy. A high-salt diet plus Hoe-140 acted synergistically
      on carotid hypertrophy and elastin content in SHR, suggesting that the role of
      endogenous bradykinin on arterial structure was amplified in the presence of a
      high-salt diet.

PMID- 9612346
TI  - ESPVR of in situ rat left ventricle shows contractility-dependent curvilinearity.
AB  - We developed a miniaturized conductance catheter for in situ rat left ventricular
      (LV) volumetry. After the validation study of the conductance volumetry in 11
      rats, we characterized the end-systolic pressure-volume relationship (ESPVR) in
      24 sinoaortic-denervated, vagotomized and urethan-anesthetized rats. Stroke
      volume (SV) measured with the conductance catheter correlated closely with that
      measured by electromagnetic flowmetry (r > 0.95). No significant difference was
      found between the in situ LV end-diastolic volumes measured by conductance
      volumetry and postmortem morphometry; a linear regression analysis indicated that
      the correlation coefficient was 0.934, that the slope was not significantly
      different from 1, and that the intercept was not significantly different from 0.
      During cardiac sympathotonic conditions, the ESPVR was curvilinear. The estimated
      slope of ESPVR (end-systolic elastance, Ees) by quadratic curve fitting at end
      systolic pressure of 100 mmHg was 2,647 +/- 846 mmHg/ml. Bilateral cervical and
      stellate ganglionectomy depressed contractility and made the ESPVR linear; a
      quadratic equation did not improve the fit. Ees was 946 +/- 55 mmHg/ml with the
      volume-axis (V0) intercept of 0.076 +/- 0.007 ml. Administration of propranolol
      (1 mg/kg) further reduced Ees (573 +/- 61 mmHg/ml, P < 0.001) and increased V0
      slightly (0.091 +/- 0.011 ml). We conclude that the conductance catheter method
      is useful for the assessment of the ESPVR of the in situ rat left ventricle and
      that the ESPVR displays contractility-dependent curvilinearity.

PMID- 9612347
TI  - Pentoxifylline attenuates reperfusion injury in skeletal muscle after partial
      ischemia.
AB  - Leukocytes have been shown to contribute to ischemia-reperfusion injury in
      skeletal muscle. Pentoxifylline (PTXF), a xanthine-derived phosphodiesterase
      inhibitor, has received recent attention because of its action on leukocytes. To
      clarify the effects of PTXF in reperfusion injury, we measured the resting
      transmembrane potential difference (Em) and evaluated postcapillary venule
      microcirculation using intravital microscopy in rat skeletal muscle during
      ischemia and reperfusion. The infrarenal aorta was clamped for 90 min and then
      reperfused for 60 min. Persistent depolarization of the resting Em was observed
      in an ischemia-reperfusion (IR) group and was significantly repolarized in a PTXF
      group during the reperfusion period. The tissue water content was significantly
      reduced in the PTXF group, although no difference was noted in the tissue lactate
      content. Flowing erythrocyte velocity and wall shear rate in the PTXF group were
      significantly higher than in the IR group during the reperfusion period but
      without significant differences in vessel diameter and hemoglobin oxygenation.
      Blood flow measured by laser-Doppler flowmeter was also significantly improved in
      the PTXF group. Furthermore, the adherent leukocyte count was significantly
      reduced in the PTXF group during this same period. These results indicate that
      PTXF attenuated reperfusion-associated membrane injury and tissue edema and that
      PTXF suppressed leukocyte adhesion and improved hindlimb blood flow during the
      reperfusion period.

PMID- 9612348
TI  - Inhibition of myocardial glucose uptake by cGMP.
AB  - Guanosine 3',5'-cyclic monophosphate (cGMP), a second messenger of nitric oxide
      (NO), regulates myocardial contractility. It is not known whether this effect is
      accompanied by a change in heart metabolism. We report here the effects of 8
      bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP), a cGMP analog, on
      regulatory steps of glucose metabolism in isolated working rat hearts perfused
      with glucose as the substrate. When glucose uptake was stimulated by increasing
      the workload, addition of the cGMP analog totally suppressed this stimulation and
      accelerated net glycogen breakdown. 8-BrcGMP did not affect pyruvate
      dehydrogenase activity but activated acetyl-CoA carboxylase, the enzyme that
      produces malonyl-CoA, an inhibitor of long-chain fatty acid oxidation. To test
      whether glucose metabolism could also be affected by altering the intracellular
      concentration of cGMP, we perfused hearts with NG-nitro-L-arginine methyl ester
      (L-NAME), an inhibitor of NO synthase, or with S-nitroso-N-acetylpenicillamine
      (SNAP), a NO donor. Perfusion with L-NAME decreased cGMP and increased glucose
      uptake by 30%, whereas perfusion with SNAP resulted in opposite effects. None of
      these conditions affected adenosine 3',5'-cyclic monophosphate concentration.
      Limitation of glucose uptake by SNAP or 8-BrcGMP decreased heart work, and this
      was reversed by adding alternative oxidizable substrates (pyruvate, beta
      hydroxybutyrate) together with glucose. Therefore, increased NO production
      decreases myocardial glucose utilization and limits heart work. This effect is
      mediated by cGMP, which is thus endowed with both physiological and metabolic
      properties.

PMID- 9612349
TI  - Mouse and rat plasma renin concentration and gene expression in (mRen2)27
      transgenic rats.
AB  - The (mRen2)27 transgenic rat [TGR(mRen2)27] is said to have low plasma levels of
      active renin. We used a direct radioimmunoassay (RIA) for mouse submaxillary
      renin, as well as an indirect enzyme-kinetic assay based on the generation of
      angiotensin I with modification of the pH optimum, to measure rat and mouse
      plasma renin activity (PRA), plasma renin concentration (PRC), and plasma
      prorenin in TGR before and after lisinopril. The relationship between rat PRC and
      % rat kidney extract was steepest at pH 6.0 and flat at pH 8.5, whereas the
      relationship between mouse PRC and purified mouse renin was steepest at pH 8.5
      and flat at pH 6.0. Mouse PRC was highly correlated with direct RIA measurements
      (r = 0.93). PRA before lisinopril was little influenced by pH, whereas the
      increase with lisinopril was greatest at pH 6.5. PRC before lisinopril was
      fourfold higher at pH 8.5 compared with that at pH 6.0. Lisinopril increased both
      PRC values but reversed the pH dependency. Prorenin was fourfold higher at pH 8.5
      compared with that at pH 6.0 and decreased slightly with lisinopril. Renal renin
      concentration was higher at pH 6.0 than at pH 8.5. With lisinopril, renal renin
      concentration increased at both pH values. Mouse PRC was not changed by
      lisinopril. Ribonuclease protection assay showed both rat and mouse renin gene
      expression in the kidney, which increased with lisinopril. Thus TGR have
      circulating active rat and mouse renin and prorenin. The notion that TGR are a
      "low renin" model should be revised.

PMID- 9612350
TI  - Ischemia-induced phosphorylation and translocation of stress protein alpha B
      crystallin to Z lines of myocardium.
AB  - It is becoming clear that stress proteins play a role in various aspects of
      postischemic myocardial recovery and that the cytoskeleton of cardiac myocytes is
      an important determinant for cellular survival during ischemia and energy
      depletion. In the present study, we addressed the question of whether the
      cytoskeleton-binding stress protein alpha B-crystallin may be involved in early
      cellular responses of rat and porcine myocardium to ischemia. Immunostaining and
      subcellular fractionation revealed a rapid ischemia-induced redistribution of
      alpha B-crystallin from a cytosolic pool to intercalated disks and Z lines of the
      myofibrils. This striking translocation of alpha B-crystallin from the cytosol to
      sites of the myofibrillar system that are known to be sensitive to ischemia
      reperfusion injury was accompanied by a rapid shift of a fraction of alpha B
      crystallin to a more acidic isoelectric point. This shift is caused by alpha B
      crystallin phosphorylation, as identified by its augmentation in the presence of
      phosphatase inhibitors (vanadate, fluoride) and comigration of the acidic alpha B
      crystallin form with the phosphorylated B1 form of lenticular alpha B-crystallin.
      In view of the chaperone-like function of alpha B-crystallin in conjunction with
      its high level of constitutive expression in the myocardium (1-2% of soluble
      protein content), we consider alpha B-crystallin an excellent candidate to play a
      role in early aspects of the protection of the myocardial contractile apparatus
      against ischemia-reperfusion injury.

PMID- 9612351
TI  - Temporally localized contributions to measures of large-scale heart rate
      variability.
AB  - The purpose of this work was to determine the temporal origins of the standard
      deviation of successive 5-min mean heart period sequences (SDANN) and the power
      of the ultralow-frequency (ULF) spectral band (< 0.0033 Hz). We hypothesized that
      SDANN and ULF might have their origins in changes in human activity rather than
      slow oscillatory rhythms. Heart period sequences were obtained from 24-h Holter
      electrocardiograms of 10 healthy ambulatory subjects. There was no evidence of
      any persistent oscillation within the ULF band. Using moving 4-h windows in short
      time Fourier transforms, we showed that the amplitude of ULF fluctuated markedly,
      particularly during times bordering sleep. The local ULF amplitude correlated (r
      = 0.59 +/- 0.09) with large-scale changes in heart period quantified with 2- and
      4-h wavelet transforms. Local SDANN also fluctuated, mainly around times of
      sleep. Although the 24-h SDANN and ULF values correlated highly, there was little
      correlation between their temporal distributions (r = 0.10 +/- 0.25). The
      temporal distributions of measures of long-range heart period variability suggest
      that they reflect changes in human activity levels.

PMID- 9612352
TI  - Cardiovascular responses attenuate with repeated NO synthesis inhibition in
      conscious fetal sheep.
AB  - The cardiovascular effects of repeated administration of the nitric oxide (NO)
      synthesis inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) were assessed
      daily for 3 days in fetal sheep near term (124-126 days gestation) beginning 4
      days after surgery (n = 7). In the first hour on day 1, fetal infusion of L-NAME
      (30 mg bolus, 6 mg/min infusion iv for 3 h) significantly increased fetal
      arterial pressure from 41 +/- 2 to 58 +/- 3 mmHg, decreased heart rate from 173
      +/- 5 to 134 +/- 3 beats/min, increased umbilicoplacental resistance from 0.16 +/
      0.02 to 0.28 +/- 0.07 mmHg.ml-1.min, and inhibited the hypotensive response to
      acetylcholine (ACh; 2 micrograms iv bolus). All changes were sustained except for
      arterial pressure, which decreased significantly to 50 +/- 3 mmHg in the third
      hour. Within 17 h, all cardiovascular variables returned to control. L-NAME
      readministered on days 2 and 3 had no effect on cardiovascular variables. L-NAME
      did not potentiate the pressor response to angiotensin II on day 2 and caused a
      surprising attenuation of the pressor response to endothelin-1 on day 3. We
      conclude that, whereas NO normally contributes to low arterial pressure, high
      heart rate, and low umbilicoplacental vascular resistance in fetal sheep near
      term, the role of NO in these functions is replaced by an alternate mechanism
      within 17 h after NO synthesis inhibition with L-NAME.

PMID- 9612353
TI  - The trabecula culture system: a novel technique to study contractile parameters
      over a multiday time period.
AB  - In the intact heart, various triggers induce alterations in gene expression that
      impact on contractile function. Because changes in gene expression reflect
      altered protein expression patterns after 12-48 h, we developed a system in which
      intact twitching cardiac trabeculae can be studied for multiday periods. Right
      ventricular trabeculae from pentobarbital sodium anesthetized rabbits were
      mounted in a sterile, closed muscle chamber. Over the first 48 h, developed force
      (Fdev) did not significantly change: 102.3 and 98.9% of the initial Fdev was
      observed after 24 and 48 h, respectively (n = 8). Also, neither diastolic force,
      time from peak to 50% relaxation (RT50), nor protein synthesis measured by a
      [3H]leucine incorporation assay changed significantly over time. Contractile
      response after > 48 h to an increase in extracellular calcium concentration (1.8
      to 2.5 mM; Fdev increased 43.5%, n = 2) or to 1 microM isoproterenol (Fdev
      increased 138.6% and RT50 decreased 34.9%, n = 2) was similar to those observed
      in freshly dissected preparations. In conclusion, this system can investigate
      contractile function of multicellular preparations under well-defined
      physiological conditions after events that alter gene and consequent protein
      expression.

PMID- 9612354
TI  - Endogenous calcitonin gene-related peptide modulates tachycardiac but not
      bradycardiac baroreflex in rats.
AB  - Effects of intracisternally administered human calcitonin gene-related peptide (8
      37) [hCGRP-(8-37)], an antagonist, and hCGRP, an agonist of the CGRP receptor in
      the rat central nervous system, on baroreflex sensitivity (BRS) were studied in
      conscious male rats. Each rat sequentially received intracisternally injected
      0.9% saline and then hCGRP-(8-37) at doses of 1, 2.5, and 5 nmol in a volume of
      10 microliters at an interval of 15 min. Five minutes after each injection,
      sodium nitroprusside (SNP, 10 micrograms/kg) or phenylephrine hydrochloride (PE,
      2 micrograms/kg) was intravenously administered to induce reflex tachycardia or
      bradycardia, respectively. Intracisternally administered hCGRP-(8-37) increased
      BRS of the reflex tachycardia induced by SNP in a dose-related manner but did not
      change the BRS after PE. Intracisternally injected hCGRP significantly decreased
      the BRS after SNP. The lowering effect of hCGRP on BRS after SNP was inhibited by
      hCGRP-(8-37) injected before hCGRP. These results suggest that endogenous CGRP in
      the lower brain stem is selectively involved in the tachycardiac but not the
      bradycardiac baroreflex and modulates the baroreflex in an inhibitory rather than
      facilitatory fashion.

PMID- 9612355
TI  - Adenosine depletion alters postictal hypoxic cerebral vasodilation in the newborn
      pig.
AB  - Altered postictal cerebral blood flow dilatory responses may contribute to brain
      injury following neonatal seizures. We developed an initial series of experiments
      to characterize the effects of seizure activity on cerebral vascular dilatory
      responses during the immediate postictal period. Significant attenuation of
      postictal hypoxic cerebral vasodilation was noted. We hypothesize that this
      diminished cerebral dilator response to hypoxia involves depletion of adenosine
      (Ado) activity resulting from seizure ictus. Additional experiments were designed
      to evaluate whether the altered postictal responses were related to a depletion
      of Ado stores or a decreased response to Ado in the postictal state. Farm-bred
      piglets were equipped with closed cranial windows. Responses to hypercapnia (10%
      CO2), hypoxia (fractional inspired O2 = 0.10), and topical sodium nitroprusside
      (10(-6) M) were compared before and after bicuculline-induced seizures (1 mg/kg).
      Hypoxia-induced cerebral vasodilation was significantly attenuated in the first
      90 min postictal (control: 56.5 +/- 6%, 10 min postictal: 6.3 +/- 2%, 60 min
      postictal: 21.7 +/- 6%, and 90 min postictal: 21.6 +/- 5%; P < 0.01), whereas the
      dilator responses to hypercapnia and topical sodium nitroprusside remained
      intact. In a separate group of piglets, both a dilating (10(-5) M) and a
      nondilating concentration of Ado (10(-11) M) were topically administered
      postictally to measure their effects on pial vessel dilatory response to hypoxia.
      Dilation to topical Ado (10(-5) M) was not altered postictally compared with
      control. Ado (10(-11) M) restored hypoxia-induced vasodilation to preseizure
      control values in the immediate postictal period (control: 51.0 +/- 8%,
      postictal: 46.7 +/- 8%, P > 0.05). Postictal administration of Ado will restore
      hypoxia-induced cerebral vasodilation in piglets even when a nondilating
      concentration is employed. This suggests that depletion of Ado with seizure
      activity is a mechanism for the loss of postictal cerebral vasodilation to
      hypoxia, and the role of Ado in hypoxic cerebral vasodilation is permissive.

PMID- 9612356
TI  - Flow-generating capability of the isolated skeletal muscle pump.
AB  - We sought to test directly whether the mechanical forces produced during rhythmic
      muscle contraction and relaxation act on the muscle vasculature in a manner
      sufficient to initiate and sustain blood flow. To accomplish this goal, we
      evaluated the mechanical performance of the isolated skeletal muscle pump. The
      hindlimb skeletal muscle pump was isolated by reversibly connecting the inferior
      vena cava and terminal aorta with extracorporeal tubing in 15- to 20-kg
      anesthetized pigs (n = 5). During electrically evoked contractions (1/s),
      hindlimb muscles were made to perfuse themselves by diverting the venous blood
      propelled out of the muscles into the shunt tubing, which had been prefilled with
      fresh arterial blood. This caused arterial blood to be pushed into the distal
      aorta and then through the muscles (shunt open, proximal aorta and vena cava
      clamped). In essence, the muscles perfused themselves for brief periods by
      driving blood around a "short-circuit" that isolates muscle from the remainder of
      the circulation, analogous to isolated heart-lung preparations. Because the
      large, short shunt offers a negligible resistance to flow, the arterial-venous
      pressure difference across the limbs was continuously zero, and thus the energy
      to drive flow through muscle could come only from the muscle pump. The increase
      in blood flow during normal heart-perfused contractions (with only the shunt
      tubing clamped) was compared with shunt-perfused contractions in which the large
      veins were preloaded with extra blood volume. Muscle blood flow increased by 87
      +/- 11 and 110 +/- 21 (SE) ml/min in the first few seconds after the onset of
      shunt-perfused and heart-perfused contractions, respectively (P > 0.4). We
      conclude that the mechanical forces produced by muscle contraction and relaxation
      act on the muscle vasculature in a manner sufficient to generate a significant
      flow of blood.

PMID- 9612357
TI  - Age-dependent responses of the mesenteric vasculature to ischemia-reperfusion.
AB  - The age-dependent responses of the mesenteric vasculature to ischemia-reperfusion
      (I/R) were compared in 2-mo-old and 2-yr-old rats. Measurements were made of
      leukocyte adherence, albumin leakage, and oxidative stress in postcapillary
      venules. In young rats I/R induced an increase in leukocyte adherence and albumin
      leakage, but in aged rats I/R induced an increase in albumin leakage without an
      increase in leukocyte adherence. Furthermore, I/R-induced oxidative stress was
      higher in the aged rats than in the young rats. To investigate whether the age
      associated oxidative stress is related to a decrease in the role of nitric oxide,
      NG-nitro-L-arginine methyl ester (L-NAME) was superfused onto the mesentery of
      young and aged rats. L-NAME induced an increase in postcapillary protein leakage
      only in young rats; however, arteriolar constriction induced by L-NAME occurred
      in both age groups. These results suggest that different mechanisms contribute to
      the inflammatory responses and microvascular dysfunction elicited by I/R in young
      and aged rats.

PMID- 9612358
TI  - Myocardial matrix metalloproteinase activity and abundance with congestive heart
      failure.
AB  - The left ventricular (LV) myocardial collagen matrix has been proposed to
      participate in the maintenance of LV geometry. Thus alterations in the
      composition of the LV myocardial collagen matrix may influence LV function. The
      matrix metalloproteinases (MMPs) are a family of enzymes that contribute to
      extracellular remodeling in several disease states. However, the types of MMPs
      expressed in the normal and congestive heart failure (CHF) state and the relation
      to MMP activity remained unclear. Accordingly, after 3 wk of pacing (240
      beats/min), changes in LV function, substrate-specific MMP activity, and MMP
      subclass abundance were measured in comparison with control pigs (n = 6). Changes
      in LV function and geometry were measured by echocardiography; LV end-diastolic
      dimension increased (3.6 +/- 0.1 vs. 6.0 +/- 0.1 cm, P < 0.05) and LV fractional
      shortening decreased (47 +/- 1 vs. 15 +/- 1%, P < 0.05) compared with controls.
      Degradation of fibrillar collagen is achieved through the combined action of
      interstitial collagenase (MMP-1), gelatinase A (MMP-2), and stromelysin (MMP-3)
      (He, C., S. Wilheilm, A. Pentland, B. Marmer, G. Grant, A. Eisen, and G.
      Goldberg. Proc. Natl. Acad. Sci. USA 86:2632-2636, 1989; Woessner, J. FASEB J. 5:
      2145-2154, 1991). Accordingly, the relative abundance of specific MMPs (MMP-1,
      MMP-2, and MMP-3) was examined by immunoblotting. With pacing CHF, the relative
      abundance for MMP-1 increased to 319 +/- 94%, MMP-2 increased to 194 +/- 31%, and
      MMP-3 increased to 493 +/- 159% (all P < 0.05). With pacing CHF, LV myocardial
      zymographic activity for the substrate gelatin increased by 119% (P < 0.05) and
      for the substrate collagen III by 153% (P < 0.05) over controls. Caseinolytic
      activity also increased with pacing CHF by 139% (P < 0.05) over controls. In
      conclusion, LV myocardial MMP activity and abundance increased with pacing
      induced CHF. These findings demonstrate that pacing-induced CHF leads to changes
      in myocardial MMP activity and expression that may be responsible for LV
      remodeling in CHF.

PMID- 9612359
TI  - Intrinsic ANG II type 1 receptor stimulation contributes to recovery of
      postischemic mechanical function.
AB  - To determine whether intrinsic angiotensin II (ANG II) type 1 receptor (AT1-R)
      stimulation modulates recovery of postischemic mechanical function, we studied
      the effects of selective AT1-R blockade with losartan on proton production from
      glucose metabolism and recovery of function in isolated working rat hearts
      perfused with Krebs-Henseleit buffer containing palmitate, glucose, and insulin.
      Aerobic perfusion (50 min) was followed by global, no-flow ischemia (30 min) and
      reperfusion (30 min) in the presence (n = 10) or absence (n = 14) of losartan (1
      mumol/l) or the cardioprotective adenosine A1 receptor agonist N6
      cyclohexyladenosine (CHA, 0.5 mumol/l, n = 11). During reperfusion in untreated
      hearts (controls), left ventricular (LV) minute work partially recovered to 38%
      of aerobic baseline, whereas proton production increased to 155%. Compared with
      controls, CHA improved recovery of LV work to 79% and reduced proton production
      to 44%. Losartan depressed recovery of LV work to 0% without altering proton
      production. However, exogenous ANG II (1-100 nmol/l) in combination with losartan
      restored recovery of LV work during reperfusion in a concentration-dependent
      manner, suggesting that postischemic recovery of function depends on intrinsic
      AT1-R stimulation.

PMID- 9612360
TI  - Involvement of SA channels in orienting response of cultured endothelial cells to
      cyclic stretch.
AB  - The present work was designed to elucidate the involvement of Ca(2+)-permeable
      stretch-activated (SA) channels in the orienting response of endothelial cells to
      uniaxial cyclic stretch. Endothelial cells from human umbilical vein were
      cultured on an elastic silicone membrane and subjected to uniaxial cyclic stretch
      (120% in length, 1 Hz). The cells started to change their morphology 15 min after
      the onset of stretch, and > 90% of the cells oriented perpendicularly to the
      stretch axis after 2 h. Associated with the orienting response, cell elongation
      proceeded with a slower rate. Both of the orientating and elongating responses
      were largely inhibited by the removal of external Ca2+ or by Gd3+, a potent
      blocker for the SA channel, but not by nifedipine. Intracellular Ca2+
      concentration ([Ca2+]i) transiently increased in response to uniaxial stretch,
      and the basal [Ca2+]i gradually increased during cyclic stretch. This Ca2+
      response was inhibited by the removal of extracellular Ca2+ or by the addition of
      Gd3+. These results suggest that stretch-dependent Ca2+ influx through SA
      channels is essential in the stretch-dependent cell orientation and elongation.

PMID- 9612361
TI  - Estrogen replacement, vascular distensibility, and blood pressures in
      postmenopausal women.
AB  - The pathogenesis of blood pressure (BP) rise in aging women remains unexplained,
      and one of the many incriminating factors may include abnormalities in arteriolar
      resistance vessels. The aim of this study was to determine the effects of
      unopposed estrogen on arteriolar distensibility, baroreceptor sensitivity (BRS),
      BP changes, and rate-pressure product (RPP). We tested the hypotheses that
      estrogen replacement therapy (ERT) enhances arteriolar distensibility and
      ameliorates BRS, which leads to decreases in BP and RPP. Postmenopausal women
      participated in a single-blind crossover study; the participants of this study,
      after baseline measurements, were randomly assigned to receive estrogen (ERT) or
      a drug-free treatment with a 6-wk washout period between treatments. The single
      blind design was instituted because subjects become unblinded due to
      physiological changes (i.e., fluid shifts, weight gain, and secretory changes)
      associated with estrogen intake. However, investigators and technicians involved
      in data collection and analyses remained blind. After each treatment, subjects
      performed identical autonomic tests, during which electrocardiograms, beat-by
      beat BPs, and respiration were recorded. The area under the dicrotic notch of the
      BP wave was used as an index of arteriolar distensibility. The magnitude of the
      reflex bradycardia after a precipitous rise in BP was used to determine BRS.
      Power spectral analysis of heart rate variability was used to assess autonomic
      activity. BPs were recorded from resistance vessels in the finger using a beat-by
      beat photoplethysmographic device. RPP, a noninvasive marker of myocardial oxygen
      consumption, was calculated. Repeated-measures analyses of variance revealed a
      significantly enhanced arteriolar distensibility and BRS after ERT (P < 0.05). A
      trend of a lower sympathovagal balance at rest was observed after ERT, however,
      this trend did not reach statistical significance (P = 0.061) compared with the
      other treatments. The above autonomic changes produced significantly lower
      systolic and diastolic BP changes and RPPs (P < 0.05) at rest and during
      isometric exercise. We conclude that short-term unopposed ERT favorably enhances
      arteriolar distensibility, BRS, and hemodynamic parameters in postmenopausal
      women. These findings have clinical implications in the goals for treating
      cardiovascular risk factors in aging women.

PMID- 9612362
TI  - Degranulation enhances release of a stable contractile factor from rabbit
      polymorphonuclear leukocytes.
AB  - We investigated the release of a stable contractile factor(s) from rabbit
      isolated polymorphonuclear leukocytes (PMNs; 10(8) cells/ml) incubated in Tyrode
      buffer at 37 degrees C. PMNs were untreated, stimulated with N-formylmethionyl
      leucyl-phenylalanine (FMLP; 0.1 microM), of degranulated with cytochalasin B (1
      microM) in combination with FMLP (0.1 microM). Products from unstimulated PMNs
      incubated for 60 min caused significantly greater contraction of rabbit isolated
      aorta (0.56 +/- 0.12 g, n = 8) than did products released from PMNs during a 5
      min incubation (0.32 +/- 0.07 g, n = 11, P < 0.05). Stimulation alone did not
      affect contractile factor release; however, products released from degranulated
      PMNs caused significantly greater aortic contraction (0.48 +/- 0.08 g, n = 5)
      than products from nondegranulated PMNs (0.24 +/- 0.04 g, n = 5, P < 0.05) after
      a 5-min incubation. The contractile activity of PMN-derived products was
      virtually abolished by heat (90 degrees C, 10 min) or protease (trypsin; 166
      U/ml, 5 h) treatment. These findings suggest a PMN-derived protein
      vasoconstrictor(s) is spontaneously released at a slow rate in vitro and that
      degranulation can enhance this rate of release. Because PMN degranulation in vivo
      is associated with inflammation, these results support suggestions that PMN
      derived contractile factors may contribute to the impaired blood flow observed
      during postischemic reperfusion.

PMID- 9612363
TI  - Central command, but not muscle reflex, stimulates cutaneous sympathetic
      efferents of cats.
AB  - We determined the effects of stimulation of the mesencephalic locomotor region
      (MLR) and the muscle reflex, each evoked separately, on the discharge of
      cutaneous sympathetic fibers innervating the hairy skin of decerebrate cats.
      Electrical stimulation of the MLR was performed while the cats were paralyzed
      with vecuronium bromide. The muscle reflex was evoked while the cats were not
      paralyzed by electrical stimulation of the tibial nerve at current intensities
      that did not activate directly group III and IV muscle afferents. MLR stimulation
      increased, on average, the discharge of the 23 cutaneous sympathetic fibers
      tested (P < 0.05). The muscle reflex, in contrast, had no overall effect on the
      discharge of 21 sympathetic fibers tested (P > 0.05). Both maneuvers markedly
      increased mean arterial pressure and heart rate (P < 0.05). Prevention of the
      baroreceptor reflex with the alpha-adrenergic blocking agent phentolamine did not
      reveal a stimulatory effect of the muscle reflex on cutaneous sympathetic
      discharge. We conclude that the MLR is a more important mechanism than is the
      muscle reflex in controlling sympathetic discharge to hairy skin during dynamic
      exercise.

PMID- 9612364
TI  - Effect of BAY y 5959 on myocardial function and metabolism in normal and failing
      hearts.
AB  - BAY y 5959 is a dihydropyridine derivative with positive inotropic actions
      mediated by a direct increase in intracellular calcium. We characterized the
      direct myocardial actions of this new agent in hearts isolated from seven normal
      dogs and from five dogs with repeated coronary microembolization-induced heart
      failure. Inotropic actions of BAY y 5959 were accompanied by little effect on
      duration of contraction and by prolongation of the monophasic action potential
      (MAP); in contrast, isoproterenol decreased contraction and MAP durations.
      Whereas inotropic responsiveness to isoproterenol was blunted in embolized
      hearts, these actions of BAY y 5959 were relatively preserved in the heart
      failure state. Isoproterenol increased heart rate, whereas BAY y 5959 had little
      effect. Changes in coronary vascular resistance also decreased similarly for
      isoproterenol and BAY y 5959. Finally, for comparable inotropy, increases in
      myocardial oxygen consumption were similar for isoproterenol and for BAY y 5959.
      In summary, preserved inotropic responsiveness and lack of positive chronotropic
      actions are two clinically favorable features of this type of inotropic agents
      compared with a typical beta-adrenergic agonist.

PMID- 9612365
TI  - Upregulation of the cardiac homeobox gene Nkx2-5 (CSX) in feline right
      ventricular pressure overload.
AB  - The recent characterization of the cardiac-specific homeobox gene Nkx2-5 (or CSX)
      and its detection in normal adult heart tissue raises the possibility of a role
      in adult hypertrophy. Using pressure overload as a primary stimulus, we used a
      feline pulmonary artery banding model to produce right ventricular hypertrophy
      (RVH). Total RNA was hybridized to a full-length murine Nkx2-5 cDNA probe that
      contained the NK family homeodomain. Nkx2-5 mRNA levels increased 5.1-fold (P <
      0.05) and 3.9-fold vs. the corresponding left ventricles at 2 and 7 days of RVH,
      respectively, during the period of maximal myocardial growth. By 2 wk, when the
      RVH response had been completed, Nkx2-5 mRNA levels were returning toward
      baseline. Hybridization with an Nkx2-5 probe not containing the NK homologous
      homeodomain demonstrated that upregulation was specific for the Nkx2-5 gene.
      Atrial natriuretic factor and alpha-cardiac actin, both activated in part by Nkx2
      5 DNA binding elements, also increased with RVH. These data suggest that a
      cardiac homeobox gene may play a role in the induction of adult cardiac
      hypertrophy.

PMID- 9612366
TI  - Insulin improves contractile function during moderate ischemia in canine left
      ventricle.
AB  - This study determined the effects of insulin on myocardial contractile function
      and glucose metabolism during moderate coronary hypoperfusion. Coronary perfusion
      pressure (CPP) was lowered from 100 to 60, 50, and 40 mmHg in the left anterior
      descending coronary artery of anesthetized, open-chest dogs. Regional glucose
      uptake (GU), lactate uptake, myocardial O2 consumption, and percent segment
      shortening (%SS) were measured without (n = 12) or with intravenous (4 U/min, n =
      12) or intracoronary insulin (4 U/min, n = 6). Glucose metabolites were also
      measured in freeze-clamped biopsies of control heart (n = 6) and hearts treated
      with intravenous insulin (n = 6) at the completion of the protocol (40 mmHg CPP).
      GU increased with intravenous and intracoronary insulin (P < 0.01). In all
      groups, GU was unaffected by reduced CPP, although lactate uptake decreased
      significantly (P < 0.01). Myocardial O2 consumption fell (P < 0.05) as CPP was
      lowered in all groups and was not altered significantly by intravenous or
      intracoronary insulin treatment. Without insulin, %SS decreased 72% (P < 0.05) at
      40 mmHg CPP, but in hearts treated with intravenous and intracoronary insulin,
      %SS was not reduced (P > 0.05). Myocardial glycogen, alanine, lactate, and
      pyruvate contents were not significantly different in untreated hearts and hearts
      treated with intravenous insulin. Thus, in moderately ischemic canine myocardium,
      insulin markedly improved regional contractile function and did not appreciably
      increase the products of anaerobic glucose metabolism.

PMID- 9612367
TI  - Cholinergic nerve function in monkey ciliary arteries innervated by nitroxidergic
      nerve.
AB  - We sought to determine the control of ciliary arterial tone by neurogenic
      acetylcholine (ACh) acting directly on smooth muscle and in conjunction with
      vasodilator nerves. Isolated posterior ciliary arteries from monkeys responded to
      ACh (10(-8)-10(-5) M) with dose-related contractions, which were endothelium
      independent. The response was not affected by cyclooxygenase inhibitors but was
      abolished by atropine. Relaxations induced at 10(-4) M ACh in the atropine
      treated arterial strips were abolished by hexamethonium and NG-nitro-L-arginine
      (L-NNA), and L-arginine (L-Arg) reversed the response suppressed by L-NNA.
      Similar results were also obtained on the nicotine (10(-4) M)-induced relaxation.
      Contractions due to transmural electrical stimulation in the endothelium-denuded
      strips treated with L-NNA were potentiated by physostigmine and depressed by
      atropine; the remaining contraction in the presence of atropine was abolished by
      prazosin. Relaxations associated with electrical stimulation, sensitive to
      tetrodotoxin, were abolished or reversed to contractions by L-NNA and restored by
      L-Arg. Stimulation-induced relaxation was attenuated by exogenous ACh and
      physostigmine and was potentiated by atropine. ACh did not affect the relaxation
      caused by nitric oxide (NO). Nerve fibers and bundles containing NADPH diaphorase
      and acetylcholinesterase were histologically demonstrated in the adventitia of
      ciliary arteries. We conclude that 1) endogenous and exogenous ACh contracts
      monkey ciliary arteries by acting on muscarinic receptors in smooth muscle cell
      membranes, 2) vasodilatation elicited by nerve stimulation with electrical pulses
      or nicotine is mediated by NO synthesized from L-Arg, 3) neurogenic ACh seems to
      interfere with the nitroxidergic nerve function by acting on prejunctional
      muscarinic receptors, and 4) high concentrations of ACh stimulate nicotinic
      receptors in vasodilator nerve terminals and promote the synthesis and/or release
      of NO.

PMID- 9612368
TI  - Step baroreflex response in awake patients undergoing carotid surgery: time- and
      frequency-domain analysis.
AB  - Step baroreceptor stimulation can provide an insight into the baroreflex control
      mechanism, yet this has never been done in humans. During carotid surgery under
      regional anesthesia, a step increase in baroreceptor stimulation occurs at
      carotid declamping immediately after removal of the intra-arterial atheromatous
      plaque. In 10 patients, the R-R interval and systolic and diastolic blood
      pressures (BP) were continuously recorded, and signals obtained within the time
      window from 10 min before until 10 min after carotid declamping were analyzed.
      Mean +/- SD time signals, power spectra, and transfer and coherence functions
      before and after declamping were calculated. Immediately after carotid
      declamping, both heart rate (HR) and BP declined in an exponential-like manner
      lasting 10.3 +/- 5.9 min, and their power spectra increased in the entire
      frequency range. Transfer function magnitude and coherence functions between BP
      and HR increased predominantly in the midfrequency region (approximately 0.1 Hz),
      with no change in phase function. Thus, in carotid endarterectomy patients, step
      increase in baroreceptor gain elicits a prolonged decline in HR and BP. Frequency
      analyses support the notion that the baroreflex control mechanism generates the
      midfrequency HR and BP variability, although other frequency regions are also
      affected.

PMID- 9612369
TI  - Acute and chronic hypokalemia sensitize the isolated heart to hypoxic injury.
AB  - We examined the effects of acute and/or chronic hypokalemia on responses to 30
      min of hypoxia and recovery in the isolated, perfused heart model. We found that
      both acute hypokalemia and chronic hypokalemia impaired contractility [expressed
      as maximum slope of pressure increase over time (dP/dt): 501 +/- 49 and 529 +/-
      48 vs. 1,302 +/- 118 mmHg/s, P < 0.01] and recovery of ATP concentrations
      (determined with 31P NMR spectroscopy: 30 +/- 6 and 40 +/- 10 vs. 67 +/- 5%
      initial, P < 0.05) at 30 min of recovery. Moreover, the combination of acute
      hypokalemia and chronic hypokalemia had additive effects (dP/dt 166 +/- 15 mmHg/s
      and ATP 21 +/- 7% initial, both P < 0.01). We also measured cytosolic calcium
      with surface fluorescence spectroscopy after indo 1 loading. Acute hypokalemia
      and acute hypokalemia + chronic hypokalemia increased cytosolic calcium (averaged
      throughout the cardiac cycle) during and after hypoxia (390- to 460-nm ratio at
      30 min of recovery: 0.46 +/- 0.07 and 0.65 +/- 0.07 vs. 0.18 +/- 0.03, P < 0.01),
      whereas control and chronic hypokalemia hearts had only small changes with
      hypoxia and recovery. Finally, when we examined mitochondria isolated from hearts
      perfused under experimental conditions, we found that chronic hypokalemia-alone
      mitochondria and chronic hypokalemia + acute hypokalemia mitochondria had marked
      impairment of state 3 respiration compared with control hearts (52 +/- 13 and 50
      +/- 9 vs. 128 +/- 10 natm.min-1.mg protein-1 with succinate as substrate, P <
      0.01), whereas acute hypokalemia mitochondria demonstrated only subtle changes.
      These data suggest that both acute hypokalemia and chronic hypokalemia impair
      cardiac responses to hypoxia. The mechanism may involve impairment of calcium
      metabolism, but cytosolic calcium alterations do not explain all of the metabolic
      and functional effects of acute hypokalemia and chronic hypokalemia in the
      setting of hypoxia.

PMID- 9612370
TI  - Venous and arterial behavior during normal pregnancy.
AB  - To assess the contribution of the arterial and venous systems in the hemodynamic
      changes of normal pregnancy, we studied blood flow, vascular resistance, venous
      tone, and the viscoelastic properties ("creep") of the upper and lower limbs
      (using plethysmography), aortic distensibility (using pulse wave velocity
      measurements), and cardiac dimensions (using echocardiography) in nine healthy
      women. Studies were longitudinally performed at the first (10-13 wk) and third
      (33-38 wk) trimesters of pregnancy in comparison with the period between the
      third and sixth month after delivery. From the first trimester, heart rate
      significantly increased while systemic blood pressure and limb vascular
      resistances did not change significantly and aortic distensibility increased (P <
      0.05). Lower limb viscoelastic properties decreased at the third trimester (P <
      0.05) and venous tone increased from the first trimester (P < 0.01), whereas
      little changes were observed at the site of upper limbs. The decrease in calf
      venous tone was significantly correlated with the increase in left ventricular
      diastolic diameter at the first (P < 0.001) and the third trimester (P < 0.05).
      The study provides evidence that during normal pregnancy, changes in the arterial
      and venous sides of the circulation occur independently of pressure alterations.
      The increase in venous tone, contributing to preload augmentation, and the
      decrease in aortic stiffness, reducing afterload, both optimize cardiac function
      until delivery.

PMID- 9612371
TI  - NO decreases phosphorylation of focal adhesion proteins via reduction of Ca in
      rat aortic smooth muscle cells.
AB  - Our laboratory has previously reported that the antimitogenic effect of nitric
      oxide (NO) in primary cultures of rat aortic smooth muscle cells may be
      attributed to activation of protein tyrosine phosphatase and dephosphorylation of
      protein phosphotyrosine [G.S. Dhaunsi, C. Matthews, K. Kaur, and A. Hassid, Am,
      J. Physiol. 272 (Heart Circ. Physiol. 41): H1342-H1349, 1997]. The goal of the
      current study was to investigate the role of cytoplasmic Ca in this process and
      to identify protein substrates that are dephosphorylated by treatment with NO.
      Treatment of primary rat aortic smooth muscle cell cultures with the NO donor S
      nitroso-N-acetylpenicillamine (SNAP) decreased cytoplasmic Ca levels and elicited
      phosphotyrosine dephosphorylation. Both effects were mimicked by the
      extracellular and intracellular Ca chelators ethylene glycol-bis(beta-aminoethyl
      ether)-N,N,N',N'-tetraacetic acid (EGTA) and 1,2-bis(2-aminophenoxy)ethane
      N,N,N',N'-tetraacetic acid (BAPTA), respectively, and by the Ca channel blocker
      nifedipine. Conversely, elevation of cytoplasmic Ca via the use of the Ca
      ionophore A-23187 or high extracellular K+ prevented or attenuated SNAP-induced
      dephosphorylation. Both BAPTA and nifedipine also decreased DNA synthesis,
      providing further evidence to link dephosphorylation to antimitogenesis. Two of
      the proteins dephosphorylated by treatment of cells with NO or EGTA were
      identified as the focal adhesion proteins, cortactin and paxillin. These results
      indicate that NO-induced dephosphorylation of protein phosphotyrosine is mediated
      by reduction of cytoplasmic Ca and suggest that dephosphorylation of focal
      adhesion proteins may be of relevance to the antimitogenic effect of NO.

PMID- 9612372
TI  - VEGF and bFGF stimulate myocardial vascularization in embryonic chick.
AB  - We tested the hypothesis that early vascularization of the embryonic heart is
      enhanced after bolus injections of vascular, endothelial growth factor (VEGF) and
      basic fibroblast growth factor (bFGF) into the vitelline vein before the onset of
      myocardial vasculogenesis (3.5 days, stage 21). Electron and light microscopy
      were utilized to obtain morphometric data. At stages 29 and 31, myocardial vessel
      volume or numerical density were higher in embryos injected with 50 ng bFGF than
      in the saline-injected controls. A VEGF injection increased vascular volume
      density at stage 29 and both volume and numerical, density at stage 31, bFGF, but
      not VEGF, was associated with an enhancement of the sinusoidal system (spongy
      layer of the ventricle) at stage 29. This effect disappeared by stage 31. In
      conclusion, 1) enhancement of bFGF or VEGF before myocardial vascularization
      increases vascular growth, but the initial effect of bFGF is greater; 2) the
      effects of these growth factors on vascular volume and numerical density are
      temporally dependent; and 3) bFGF, in addition to its effects on the coronary
      vasculature, influences ventricular modeling by apparently acting on myocytes as
      well as endothelial cells.

PMID- 9612373
TI  - Magnetic resonance myocardial fiber-orientation mapping with direct histological
      correlation.
AB  - Functional properties of the myocardium are mediated by the tissue structure.
      Consequently, proper physiological studies and modeling necessitate a precise
      knowledge of the fiber orientation. Magnetic resonance (MR) diffusion tensor
      imaging techniques have been used as a nondestructive means to characterize
      tissue fiber structure; however, the descriptions so far have been mostly
      qualitative. This study presents a direct, quantitative comparison of high
      resolution MR fiber mapping and histology measurements in a block of excised
      canine myocardium. Results show an excellent correspondence of the measured fiber
      angles not only on a point-by-point basis (average difference of -2.30 +/- 0.98
      degrees, n = 239) but also in the transmural rotation of the helix angles
      (average correlation coefficient of 0.942 +/- 0.008 with average false-positive
      probability of 0.004 +/- 0.001, n = 24). These data strongly support the
      hypothesis that the eigenvector of the largest MR diffusion tensor eigenvalue
      coincides with the orientation of the local myocardial fibers and underscore the
      potential of MR imaging as a noninvasive, three-dimensional modality to
      characterize tissue fiber architecture.

PMID- 9612374
TI  - Arterial baroreflex during pregnancy and renal sympathetic nerve activity during
      parturition in rabbits.
AB  - The arterial baroreflex control of renal sympathetic nerve activity (RSNA) was
      evaluated in nine term pregnant (P) and 12 nonpregnant (NP) conscious New Zealand
      White rabbits. In an additional four P rabbits, the RSNA response to spontaneous
      parturition was measured. The blood pressure (BP)-RSNA relationship was generated
      by sequential inflations of aortic and vena caval perivascular occluders. Rest BP
      (P: 61 +/- 2 vs. NP: 73 +/- 2 mmHg) and the centering point of the baroreflex (P:
      57 +/- 2 vs. NP: 70 +/- 2 mmHg) were lower (P < 0.05) in term pregnancy.
      Baroreflex range (P: 246 +/- 14% vs. NP 263 +/- 24% of rest RSNA) was not
      affected by pregnancy. However, maximal reflex gain was moderately depressed (
      44%) in P rabbits (P: -15 +/- 1 vs. NP: -27 +/- 4% of rest RSNA/mmHg; P < 0.05)
      due to a significant reduction in the slope coefficient. Delivery of a fetus was
      associated with strong renal sympatho-excitation. Peak RSNA averaged 80 +/- 37%
      of smoke-elicited RSNA or 1,221 +/- 288% of rest RSNA (mean +/- SD). These
      results suggest that, in contrast to rat pregnancy, depressed arterial baroreflex
      control of RSNA in rabbit pregnancy is due primarily to a reduction in maximal
      gain rather than a reduction in the maximal sympathetic response to hypotension.

PMID- 9612375
TI  - Multiple effects of KPQ deletion mutation on gating of human cardiac Na+ channels
      expressed in mammalian cells.
AB  - Several aspects of the effect of the KPQ deletion mutation on Na+ channel gating
      remain unresolved. We have analyzed the kinetics of the early and late currents
      by recording whole cell and single-channel currents in a human embryonic kidney
      (HEK) cell line (HEK293) expressing wild-type and KPQ deletion mutation in
      cardiac Na+ channels. The rate of inactivation increased three- to fivefold
      between -40 and -80 mV in the mutant channel. The rate of recovery from
      inactivation was increased twofold. Two modes of gating accounted for the late
      current: 1) isolated brief openings with open times that were weakly voltage
      dependent and the same as the initial transient and 2) bursts of opening with
      highly voltage-dependent prolonged open times. Latency to first opening was
      accelerated, suggesting an acceleration of the rate of activation. The delta KPQ
      mutation has multiple effects on activation and inactivation. The aggregate
      effects may account for the increased susceptibility to arrhythmias.

PMID- 9612376
TI  - Effect of chronic sensory denervation on Ca(2+)-induced relaxation of isolated
      mesenteric resistance arteries.
AB  - We recently reported that Ca(2+)-induced relaxation could be linked to a Ca2+
      receptor (CaR) present in perivascular nerves. The present study assessed the
      effect of chronic sensory denervation on Ca(2+)-induced relaxation. Mesenteric
      resistance arteries were isolated from rats treated as neonates with capsaicin
      (50 mg/kg), vehicle, or saline. The effect of cumulative addition of Ca2+ was
      assessed in vessels precontracted with 5 microM norepinephrine.
      Immunocytochemical studies showed that capsaicin treatment significantly reduced
      the density of nerves staining positively for calcitonin gene-related peptide
      (CGRP) and for the CaR (CGRP density: control, 51.1 +/- 3.9 microns2/mm2;
      capsaicin treated, 31.4 +/- 2.8 microns2/mm2, P = 0.01; control CaR density, 46
      +/- 4 microns2/mm2, n = 7; capsaicin-treated CaR density, 24 +/- 4 microns2/mm2,
      n = 8, P = 0.002). Dose-dependent relaxation to Ca2+ (1-5 mM) was significantly
      depressed in vessels from capsaicin-treated rats (overall P < 0.001, n = 6 or 7),
      whereas the relaxation response to acetylcholine remained intact. These data
      support the hypothesis that Ca(2+)-induced relaxation is mediated by activation
      of the CaR associated with capsaicin-sensitive perivascular neurons.

PMID- 9612377
TI  - Mechanism of volume adaptation in the awake early pregnant rat.
AB  - The objective of the present study was to determine whether the increase in
      plasma volume (PV) during pregnancy is established by fluid retention or by a
      shift within the extracellular fluid volume (ECFV) from the interstitium toward
      the intravascular compartment. To this end, we simultaneously, measured total
      body water, (TBW), ECFV, and PV together with the hematocrit (Hct) and plasma
      osmolality 4, 8, and 12 days postsurgery in chronically instrumented pregnant (P)
      and nonpregnant (NP) rats. The P rats were instrumented with a catheter in the
      femoral artery on day 1 postconception. In the NP group, neither TBW nor ECFV and
      PV had changed consistently on days 8 and 12 postsurgery relative to day 4. In
      contrast, in the P animals, TBW, ECFV, and PV had increased by 16, 24, and 20%,
      respectively, by day 12 relative to day 4. To evaluate whether PV had increased
      in concert with an overall rise in TBW or as a result of a fluid shift at the
      cost of the interstitial fluid volume, we calculated the relative size of each
      fluid compartment on three consecutive measurement sessions. In the NP group,
      TBW, presented as percentage of maternal weight (%MW) as well as ECFV (%TBW) and
      PV (%ECFV) had not changed consistently throughout the measurement period. In the
      P animals, TBW (%MW) was slightly higher on day 12 compared with day 4, but ECFV
      (%TBW) and PV (%ECFV) had not changed significantly. Finally, in the NP group,
      Hct had not changed, whereas, in the P animals, Hct was 10% lower on days 8 and
      12 compared with day 4. Plasma osmolality did not change consistently in either
      group during the course of the experimental period. The gradual synchronous
      increase in all fluid compartments, without consistent change in their relative
      distribution, suggests that, in normal rat pregnancy, PV expansion is primarily
      achieved by fluid retention rather than by a redistribution of the ECFV.

PMID- 9612378
TI  - Mechanisms of the cardiovascular deconditioning induced by tail suspension in the
      rat.
AB  - The aim of the present work was to obtain insights into the pathophysiology of
      cardiovascular deconditioning (CVD) induced by tail suspension (TS) in the rat:
      during TS, when central venous pressure (CVP) has been normalized (E. Martel, P.
      Champeroux, P. Lacolley, S. Richard, M. Safar, and J. L. Cuche. J. Appl. Physiol.
      80: 1390-1396, 1996), and during simulated orthostatism (SO), when transient
      episodes of hypotension and bradycardia are disclosed, bradycardia with SO
      represents a response that seems peculiar to the rat compared with humans.
      According to basic physiology, a reduced activity of the sympathetic system
      induced by increased CVP was suspected but was not supported by data obtained
      through spectral analysis of blood pressure (BP) and heart rate (HR) variability
      or measurements of plasma catecholamine concentration during TS. Nonetheless,
      indirect evidence was obtained. During SO, plasma catecholamine concentration was
      lower in TS rats than in controls, suggesting a reduced synthesis of
      catecholamines, itself secondary to reduced activity of the sympathetic system.
      Furthermore, after 48 h of TS, the number of binding sites and affinity of alpha
      receptors in rat aorta were increased, compatible with a reduced level of
      neurotransmitter in the synaptic cleft. A second series of experiments was
      carried out to study hypotension and bradycardia in TS rats during SO.
      Hypersensitivity of serotonergic mechanisms was suspected. Two 5-HT3 receptor
      antagonists (ondansetron and MDL-72222) blocked hypotension and restored
      tachycardia, basic features of orthostatic adaptation of the circulatory system.
      Response to the 5-HT3 receptor agonist was measured through dose-response curves
      of BP and HR after injection of 2-methylserotonin. After low doses, hypotension
      (10 micrograms/kg) and bradycardia (3 and 10 micrograms/kg) were significantly
      greater in 48-h TS rats than in controls. Thus CVD in the rat induced by TS
      appears to implicate at least two mechanisms: reduced activity of the sympathetic
      system and hypersensitivity of serotonergic mechanisms.

PMID- 9612379
TI  - ATP-dependent K+ channel activation reduces loss of opioid dilation after brain
      injury.
AB  - ATP-dependent K+ (KATP) channel function is impaired after fluid percussion brain
      injury (FPI). Additionally, the nitric oxide (NO) releaser sodium nitroprusside
      and a cGMP analog elicit pial dilation via KATP channel activation, whereas
      opioids such as methionine enkephalin (Met) elicit pial dilation via NO and KATP
      channel activation. Decremented Met dilation contributes to reductions in pial
      artery diameter and altered cerebral hemodynamics after FPI. This study was
      designed to investigate the role of KATP channel activation before FPI in the
      loss of opioid dilation subsequent to FPI in newborn pigs equipped with a closed
      cranial window. FPI was produced by allowing a pendulum to strike a piston on a
      saline-filled cylinder that was fluid coupled to the brain via a hollow screw in
      the cranium. FPI blunted dilation to Met (7 +/- 1, 11 +/- 1, and 17 +/- 1% before
      FPI vs. 1 +/- 1, 4 +/- 1, and 6 +/- 1% after FPI for 10(-10), 10(-8), and 10(-6)
      M Met, respectively). Met-associated elevation in cerebrospinal fluid (CSF) cGMP
      was similarly blunted (350 +/- 12 and 636 +/- 12 fmol/ml before FPI vs. 265 +/- 5
      and 312 +/- 17 fmol/ml after FPI for control and 10(-6) M Met, respectively). In
      piglets pretreated with cromakalim (10(-10) M) 20 min before FPI, Met dilation
      was partially restored (7 +/- 1, 10 +/- 1, and 15 +/- 1% before FPI vs. 4 +/- 1,
      7 +/- 1, and 11 +/- 1% after FPI for 10(-10), 10(-8), and 10(-6) M Met,
      respectively). Met cGMP release was similarly partially restored (400 +/- 9 and
      665 +/- 25 fmol/ml before FPI vs. 327 +/- 11 and 564 +/- 23 fmol/ml after FPI for
      control and 10(-6) Met, respectively). Cromakalim (10(-10) M) had no effect on
      pial diameter itself but prevented pial artery constriction by FPI (148 +/- 5 to
      124 +/- 5 microns vs. 139 +/- 4 to 141 +/- 4 microns in the absence vs. presence
      of cromakalim pretreatment, respectively). In contrast, pretreatment with a
      subthreshold concentration of NS-1619, a calcium-dependent K+ channel agonist,
      did not restore vascular and biochemical parameters after FPI. These data
      indicate that prior KATP channel activation reduces the loss of opioid dilation
      after FPI.

PMID- 9612380
TI  - Differential atrial and ventricular expression of myocardial BNP during evolution
      of heart failure.
AB  - Although brain natriuretic peptide (BNP) of myocardial origin is important in
      cardiovascular and renal function and as a marker of cardiac dysfunction, the
      expression of BNP in atrial and ventricular myocardium remains controversial both
      under normal conditions and in heart failure. We therefore determined left atrial
      and left ventricular (LV) gene expression and tissue concentration as well as
      circulating BNP during the evolution of rapid ventricular pacing-induced
      congestive heart failure (CHF) in the dog. Early LV dysfunction after 10 days of
      pacing was characterized by impaired LV function but maintained arterial
      pressure, and overt CHF after 38 days of pacing was characterized by further
      impaired LV function and decreased systemic arterial pressure. Under normal
      conditions, cardiac BNP mRNA and cardiac tissue BNP were of atrial origin. In
      early LV dysfunction, BNP mRNA and tissue BNP were markedly increased in the left
      atrium in association with an increase in circulating BNP but remained below or
      at the limit of detection in the LV. In overt CHF, BNP mRNA was further increased
      in the left atrium and first increased in the LV, together with an increase in LV
      tissue BNP and a further increase in circulating BNP. In the progression of CHF,
      early LV dysfunction is characterized by a selective increase in atrial BNP
      expression in association with increased circulating BNP. Overt CHF is
      characterized by an additional recruitment of ventricular BNP expression and a
      further increase in circulating BNP. These studies provide important new insight
      into the local and temporal regulation of cardiac BNP gene expression during the
      progression of heart failure and underscore the predominant endocrine role of
      atrial myocardium under normal conditions and in early LV dysfunction.

PMID- 9612381
TI  - D-[Ala2]endomorphin 2 and endomorphin 2 have nitric oxide-dependent vasodilator
      activity in rats.
AB  - Endomorphin 1 and 2, newly discovered endogenous ligands for the mu-opioid
      receptor, have vasodepressor activity in the rat. In the present study, the
      mechanism mediating hemodynamic responses to endomorphin 2 and the endomorphin
      analog [D-Ala2]endomorphin 2 (TAPP) was investigated in the rat. Intravenous
      injections of TAPP and endomorphin 2 produced similar dose-dependent decreases in
      systemic arterial pressure and were approximately 10-fold more potent than Met
      enkephalin. TAPP and endomorphin 2 decreased heart rate, cardiac output, and
      total peripheral resistance. Under constant-flow conditions, injections of TAPP
      and endomorphin 2 into the perfusion circuit produced decreases in hindquarter
      perfusion pressure, and vasodilator responses were attenuated by the opioid
      receptor antagonist naloxone. Hindquarter vasodilator responses to TAPP and
      endomorphin 2 were attenuated by the nitric oxide synthase inhibitor N omega
      nitro-L-arginine methyl ester (L-NAME; 50 mg/kg iv), whereas responses to the
      endothelium-independent vasodilators calcitonin gene-related peptide,
      diethylamine/nitric oxide, and isoproterenol were not changed. Hindquarter
      vasodilator responses to TAPP and endomorphin 2 were not altered by the
      cyclooxygenase inhibitor sodium meclofenamate, the ATP-dependent K+ channel
      antagonist U-37883A, or the presence of a time-delay coil in the perfusion
      circuit. These results indicate that vasodilator responses to TAPP and
      endomorphin 2 are mediated by the activation of a naloxone-sensitive opioid
      receptor and the release of nitric oxide from the endothelium within the
      hindquarter vascular bed of the rat.

PMID- 9612382
TI  - Tyrosine confounds oxidative electrochemical detection of nitric oxide.
AB  - We report evidence that a porphyrinic microsensor for detection of nitric oxide
      (NO) also detects biologically relevant concentrations of tyrosine (Tyr) in dog
      brain. Tyr is oxidized by this sensor at the same potential as NO, and the
      sensitivity for NO and Tyr are of the same order of magnitude. The interference
      from Tyr is of importance because 1) Tyr is abundant and 2) there is a
      concentration gradient of Tyr across the blood-brain barrier that can lead to
      unpredictable results if disturbed by ischemia or hypoxia. The knowledge of this
      interference is important for the interpretation of results obtained with this
      sensor and for the design of future studies.

PMID- 9612383
TI  - Effective diffusion distance of nitric oxide in the microcirculation.
AB  - Despite its well-documented importance, the mechanism for nitric oxide (NO)
      transport in vivo is still unclear. In particular, the effect of hemoglobin-NO
      interaction and the range of NO action have not been characterized in the
      microcirculation, where blood flow is optimally regulated. Using a mathematical
      model and experimental data on NO production and degradation rates, we
      investigated factors that determine the effective diffusion distance of NO in the
      microcirculation. This distance is defined as the distance within which NO
      concentration is greater than the equilibrium dissociation constant (0.25 microM)
      of soluble guanylyl cyclase, the target enzyme for NO action. We found that the
      size of the vessel is an important factor in determining the effective diffusion
      distance of NO. In approximately 30- to 100-micron-ID microvessels the luminal NO
      concentrations and the abluminal effective diffusion distance are maximal.
      Furthermore, the model suggests that if the NO-erythrocyte reaction rate is as
      fast as the rate reported for the in vitro NO-hemoglobin reaction, the NO
      concentration in the vascular smooth muscle will be insufficient to stimulate
      smooth muscle guanylyl cyclase effectively. In addition, the existence of an
      erythrocyte-free layer near the vascular wall is important in determining the
      effective NO diffusion distance. These results suggest that 1) the range of NO
      action may exhibit significant spatial heterogeneity in vivo, depending on the
      size of the vessel and the local chemistry of NO degradation, 2) the NO binding/
      reaction constant with hemoglobin in the red blood cell may be much smaller than
      that with free hemoglobin, and 3) the microcirculation is the optimal site for NO
      to exert its regulatory function. Because NO exhibits vasodilatory function and
      antiatherogenic activity, the high NO concentration and its long effective range
      in the microcirculation may serve as intrinsic factors to prevent the development
      of systemic hypertension and atherosclerotic pathology in microvessels.

PMID- 9612384
TI  - Interaction among autoregulation, CO2 reactivity, and intracranial pressure: a
      mathematical model.
AB  - The relationships among cerebral blood flow, cerebral blood volume, intracranial
      pressure (ICP), and the action of cerebrovascular regulatory mechanisms
      (autoregulation and CO2 reactivity) were investigated by means of a mathematical
      model. The model incorporates the cerebrospinal fluid (CSF) circulation, the
      intracranial pressure-volume relationship, and cerebral hemodynamics. The latter
      is based on the following main assumptions: the middle cerebral arteries behave
      passively following transmural pressure changes; the pial arterial circulation
      includes two segments (large and small pial arteries) subject to different
      autoregulation mechanisms; and the venous cerebrovascular bed behaves as a
      Starling resistor. A new aspect of the model exists in the description of CO2
      reactivity in the pial arterial circulation and in the analysis of its nonlinear
      interaction with autoregulation. Simulation results, obtained at constant ICP
      using various combinations of mean arterial pressure and CO2 pressure,
      substantially support data on cerebral blood flow and velocity reported in the
      physiological literature concerning both the separate effects of CO2 and
      autoregulation and their nonlinear interaction. Simulations performed in dynamic
      conditions with varying ICP underline the existence of a significant correlation
      between ICP dynamics and cerebral hemodynamics in response to CO2 changes. This
      correlation may significantly increase in pathological subjects with poor
      intracranial compliance and reduced CSF outflow. In perspective, the model can be
      used to study ICP and blood velocity time patterns in neurosurgical patients in
      order to gain a deeper insight into the pathophysiological mechanisms leading to
      intracranial hypertension and secondary brain damage.

PMID- 9612385
TI  - Modeling cerebral autoregulation and CO2 reactivity in patients with severe head
      injury.
AB  - The mathematical model presented in a previous work is used to simulate the time
      pattern of intracranial pressure (ICP) and of blood velocity in the middle
      cerebral artery (VMCA) in response to maneuvers simultaneously affecting mean
      systemic arterial pressure (SAP) and end-tidal CO2 pressure. In the first stage
      of this study, a sensitivity analysis was performed to clarify the role of some
      important model parameters [cerebrospinal fluid (CSF) outflow resistance,
      intracranial elastance coefficient, autoregulation gain, and the position of the
      regulation curve] during CO2 alteration maneuvers performed at different SAP
      levels. The results suggest that the dynamic "ICP-VMCA" relationship obtained
      during changes in CO2 pressure may contain important information on the main
      factors affecting intracranial dynamics. In the second stage, the model was
      applied to the reproduction of real ICP and velocity tracings in neurosurgical
      patients. Ten distinct tracings, taken from six patients during CO2 changes at
      different mean SAP levels, were reproduced. Best fitting between model and
      clinical curves was achieved by minimizing a least-squares criterion function and
      adjusting certain parameters that characterize CSF circulation, intracranial
      compliance, and the strength of the regulation mechanisms. A satisfactory
      reproduction was achieved in all cases, with parameter numerical values in the
      ranges reported in clinical literature. It is concluded that the model may be
      used to give reliable estimations of the main factors affecting intracranial
      dynamics in individual patients, starting from routine measurements performed in
      neurosurgical intensive care units.

PMID- 9612386
TI  - PDGF-BB-induced DNA synthesis is delayed by angiotensin II in vascular smooth
      muscle cells.
AB  - The interaction of ANG II with platelet-derived growth factor (PDGF)-BB-induced
      DNA synthesis was studied in cultured rat aortic smooth muscle cells. PDGF-BB
      induced DNA synthesis was delayed (approximately 6-8 h) by ANG II as shown by a
      time-course experiment. Losartan, an AT1-receptor antagonist, blocked the
      transient inhibitory effect of ANG II, whereas the AT2-receptor antagonist PD
      123319 had no effect. Autocrine- or paracrine-acting transforming growth factor
      beta 1 (TGF-beta 1), believed to be a mediator of ANG II-induced inhibitory
      effects, was not responsible for the delay of PDGF-BB-induced DNA synthesis,
      because a potent TGF-beta 1 neutralizing antibody could not reverse this effect
      of ANG II, nor was the delay of the PDGF-BB effect caused by inhibition of PDGF
      beta-receptor phosphorylation as shown by Western blot analysis of
      immunoprecipitated PDGF-beta receptor. In conclusion, our results show that ANG
      II can exert a transient inhibitory effect on PDGF-BB-induced proliferation via
      the AT1 receptor.

PMID- 9612387
TI  - In vivo and in vitro mechanical properties of the sheep thoracic aorta in the
      perinatal period and adulthood.
AB  - The mammalian aorta undergoes rapid remodeling during the perinatal period and
      more gradual remodeling during subsequent development, but the implications of
      this remodeling for arterial mechanics are poorly understood. In this study in
      vivo and in vitro techniques were used to determine the static and viscoelastic
      properties of the thoracic aortas of 119-day-gestation fetal sheep (full term =
      145 days), 21-day-old lambs, and adult sheep at control distending pressures and
      after 70% increases or 30% decreases in pressure. In the weeks surrounding birth,
      aortic wall tissue became substantially stiffer (static elastic modulus in vitro
      increased by 28%, and pressure wave velocity in vivo increased by 61%) but less
      viscous (pressure wave attenuation in vivo decreased by 46%, and viscoelastic
      phase angle in vitro decreased by 15%), whereas the wall thickness-to-radius
      ratio was unchanged. By contrast, modest changes in tissue viscoelasticity from
      neonatal to adult life were accompanied by a halving of the wall thickness-to
      radius ratio from 0.19 +/- 0.01 to 0.10 +/- 0.01. The relative thinning of the
      vessel wall, combined with a doubling of blood pressure after birth, resulted in
      a 265% increase in aortic wall tensile stress over the period of study. We
      concluded that rapid remodeling in the perinatal period primarily alters the
      viscoelastic properties of aortic wall tissues, whereas more gradual postnatal
      remodeling largely affects vessel geometry.

PMID- 9612388
TI  - R-R variability detects increases in vagal modulation with phenylephrine
      infusion.
AB  - High-frequency power, measured from power spectral analysis of R-R variability,
      reflects vagal modulation of the sinus node. Unexpectedly, a recent study
      reported a decrease in high-frequency power during the infusion of phenylephrine
      despite a prolongation of R-R intervals, indicating an increase in vagal
      activity. To better define the limitations of high-frequency power to quantify
      vagal modulation, we measured high-frequency power during the infusion of
      phenylephrine (0.4, 0.8, and 1.2 micrograms.kg-1.min-1) into 10 normal subjects.
      We found increasing doses of phenylephrine produced progressive increases in
      systolic blood pressure from 118 +/- 4 to 129 +/- 5 mmHg (P < 0.005), R-R
      intervals from 881 +/- 44 to 1,274 +/- 69 ms (P < 0.0001), and the logarithm of
      high-frequency power from 5.83 +/- 0.22 to 7.73 +/- 0.24 ln(ms2) (P < 0.0001).
      The conclusion was high-frequency power increases with increasing doses of
      phenylephrine. These data strongly support the ability of high-frequency power to
      detect an increase in vagal modulation during baroreceptor activation from an
      increase in systolic blood pressure with the infusion of phenylephrine.

PMID- 9612389
TI  - Regional expansion during myocardial ischemia predicts ventricular fibrillation
      and coronary reocclusion.
AB  - Primary ventricular fibrillation (VF) complicating acute myocardial infarction is
      associated with occluded infarction-related arteries. The relationship between VF
      during ischemia and spontaneous coronary reocclusion was analyzed in 48
      anesthetized pigs submitted to 48 min of coronary ligation and 6 h of reflow.
      Reocclusion was associated with ischemic VF (6 of 11 animals with VF but only 6
      of 37 without it had reocclusion) but not with reperfusion arrhythmias, the size
      of the ischemic area, the magnitude of electrocardiogram changes or contractile
      dysfunction during ischemia, or the severity of intimal injury at the occlusion
      site. The increase in end-diastolic length in the ischemic region during coronary
      occlusion was associated with ischemic VF (15 min after occlusion, end-diastolic
      length was 116 +/- 2 and 111 +/- 1% of baseline in animals with or without
      presenting subsequent VF, respectively) and was retained by multiple logistic
      regression analysis as the only independent predictor of ischemic VF and
      reocclusion. Thus ischemic VF is strongly associated with an increased rate of
      spontaneous coronary reocclusion during subsequent reperfusion. Acute expansion
      of ischemic myocardium appears as a prominent determinant of both ischemic VF and
      reocclusion.

PMID- 9612390
TI  - Inhibition of nitric oxide synthesis increases venular permeability and alters
      endothelial actin cytoskeleton.
AB  - Inhibition of nitric oxide (NO) synthesis using NG-nitro-L-arginine methyl ester
      (L-NAME) or NG-monomethyl-L-arginine (L-NMMA) increases venular permeability in
      the rat mesentery (I. Kurose, R. Wolf, M. B. Grisham, T. Y. Aw, R. D. Specian,
      and D. N. Granger. Circ. Res. 76: 30-39, 1995), but the cellular mechanisms of
      this response are not known. This study was performed to determine whether such
      venular leaks are associated with changes in the endothelial actin cytoskeleton.
      In anesthetized Sprague-Dawley rats, the microvasculature of a mesenteric window
      was perfused with buffered saline, with or without 10(-5) M L-NAME, L-NMMA, or
      the inactive enantiomer NG-nitro-D-arginine methyl ester for 3 or 30 min. FITC
      albumin was added to the perfusate for the last 3 min. The vasculature was
      perfusion fixed, stained for filamentous actin and for mast cells, and viewed
      microscopically. In control preparations, venules showed few FITC-albumin leaks
      and the endothelial actin cytoskeleton consisted of a peripheral rim along the
      cell-cell junctions. Preparations treated with L-NAME or L-NMMA showed
      significantly more leakage, the actin rims in leaky venules were discontinuous,
      and short, randomly oriented fibers appeared within the cells. In nonleaky
      venules, the peripheral actin rims sometimes contained small, equally spaced
      discontinuities not seen in control preparations. Although a mast cell stabilizer
      was used, 27-70% of the mast cells were degranulated in the presence of L-NMMA.
      Thus inhibition of NO synthesis alters the endothelial cytoskeleton and increases
      albumin leakage from mesenteric venules, either directly or indirectly via the
      involvement of mast cells.

PMID- 9612391
TI  - Gene-targeted mice reveal importance of L-selectin-dependent rolling for
      neutrophil adhesion.
AB  - It has not been determined whether L-selectin-mediated rolling can promote
      leukocyte adhesion in vivo independent of P- and E-selectin. We used intravital
      microscopy of E- and P-selectin double-mutant mice (E-/P-) stimulated with tumor
      necrosis factor-alpha for 6-8 h to investigate the importance of L-selectin
      dependent rolling in cremaster muscle venules. Rolling leukocyte flux in E-/P-
      mice was 9 +/- 2 cells/min compared with 77 +/- 17 cells/min in wild-type (WT)
      mice. Pretreatment with the L-selectin monoclonal antibody MEL-14 significantly
      reduced rolling in both E-/P- (by 89%) and WT mice (by 79%). L-selectin-dependent
      rolling in E-/P- mice resulted in leukocyte adhesion comparable to that seen in
      WT mice. MEL-14 pretreatment of E-/P- mice reduced leukocyte adhesion by 50%. The
      majority (approximately 80%) of intravascular leukocytes in both WT and E-/P-
      mice were neutrophils. We conclude that L-selectin can mediate rolling that
      results in sufficient leukocyte recruitment to account for the robust
      inflammatory response seen in E-/P- mice at later times.

PMID- 9612392
TI  - Blunted hypoxic pulmonary vasoconstrictive response in the rodent Ochotona
      curzoniae (pika) at high altitude.
AB  - To investigate the possible mechanisms of adaptation to chronic hypoxia in the
      pulmonary circulation, we made direct measurements of pulmonary arterial pressure
      (Ppa) in 10 awake pika rodents that were transported to Xining, People's Republic
      of China (altitude 2,260 m) after being captured at 4,300 m and in 10 Wistar rats
      in a decompression chamber (simulated altitudes of 4,300 and 5,000 m) in Xining.
      Ppa was obtained at 1 h of exposure to each simulated altitude. The histology and
      immunohistochemistry of the lung tissues were also studied. Ppa in the pikas
      after the 4,300- and 5,000-m altitude exposures did not significantly increase,
      whereas in the rats Ppa rose significantly. Mean changes in Ppa from 2,260 to
      4,300 and 5,000 m were 1.48 +/- 0.49 and 4.80 +/- 0.67 mmHg in the pikas and
      10.38 +/- 3.36 and 19.10 +/- 2.28 mmHg in the rats. The ratio of right
      ventricular to left ventricular plus septal weight in the pikas and rats was 0.22
      and 0.45, respectively. The pikas maintained levels of Hb, hematocrit, and 2,3
      diphosphoglycerate lower than those of the rats. The percent wall thickness of
      the small pulmonary arteries in the pikas and rats was 9.22 and 27.21%,
      respectively, and it was well correlated with the degree of Ppa in both groups.
      Mast cells were observed in the lungs of the rats (7.1 +/- 0.33 cells/mm2) but
      not in the pikas. There was highly positive staining for mast cell tryptase and
      transforming growth factor-beta around pulmonary vessels in the rats, whereas no
      demonstrable reaction was observed in the pikas. We conclude that the pika has
      adapted to high altitude by losing hypoxic pulmonary vasoconstriction and thin
      walled pulmonary arterioles.

PMID- 9612393
TI  - Subcellular properties of [Ca2+]i transients in phospholamban-deficient mouse
      ventricular cells.
AB  - The regulatory protein phospholamban exerts a physiological inhibitory effect on
      the sarcoplasmic reticulum (SR) Ca2+ pump that is relieved with phosphorylation.
      We have studied the subcellular properties of intracellular Ca2+ ([Ca2+]i)
      transients in ventricular myocytes isolated from wild-type (WT) and phospholamban
      deficient (PLB-KO) mice. In PLB-KO myocytes, steady-state twitch [Ca2+]i
      transients revealed an accelerated relaxation and the occurrence of highly
      localized failures of Ca2+ release. The acceleration of SR Ca2+ uptake caused an
      increase in SR Ca2+ load with the frequent occurrence of spontaneous [Ca2+]i
      waves and Ca2+ sparks. [Ca2+]i waves in PLB-KO cells showed a marked decrease in
      spatial width and more frequently appeared to abort. Local Ca2+ release events
      (Ca2+ sparks) were larger and more variable in amplitude and [Ca2+]i declined
      faster in PLB-KO myocytes. Increased local buffering and reduction in the
      refractoriness of SR Ca2+ release caused by the increased SR pump rate led to an
      overall enhancement of local [Ca2+]i gradients and inhomogeneities in the [Ca2+]i
      distribution during spontaneous Ca2+ release, [Ca2+]i waves, and excitation
      contraction coupling.

PMID- 9612394
TI  - Ventricular remodeling in a mouse model of myocardial infarction.
AB  - We investigated the suitability of studying ventricular remodeling in a mouse
      model of myocardial infarction (MI). We performed left coronary ligation (n = 22)
      or a sham procedure (n = 21) on normal C57BL/6J mice. Six weeks later, animals
      underwent echocardiography and hemodynamic evaluation. Left ventricular (LV)
      volume at a common distending pressure was calculated from passive pressure
      volume curves. The MI group exhibited lower systolic blood pressure (P < 0.05),
      higher LV end-diastolic pressure (P < 0.05), and lower peak first derivative of
      LV pressure (dP/dt, P < 0.05) than the sham group. Mice with moderate (< 40%, n =
      11) and large (> or = 40%, n = 11) MIs displayed increased LV mass-to-body weight
      ratio (P < 0.02 and P < 0.01, respectively, vs. sham group), whereas only the
      large-MI group exhibited increased right ventricular mass-to-body weight ratio (P
      < 0.01). LV volumes were increased in the moderate-MI group (P = 0.059 vs. sham
      group) and to a much greater extent in the large-MI group (P < 0.0001 vs. sham
      group). The moderate- and large-MI groups also exhibited increases in LV end
      diastolic diameter (P < 0.03 and P < 0.0001, respectively, vs. sham group) and LV
      end-systolic diameter (P < 0.01 and P < 0.0001, respectively, vs. sham group)
      with decreased fractional shortening (P < 0.01 for both). These data demonstrate
      ventricular remodeling in a mouse model of MI and confirm the feasibility of
      quantifying indexes of remodeling in vivo and postmortem. This model will be of
      particular usefulness when applied to transgenic strains.

PMID- 9612395
TI  - Intracellular calcium dynamics in mouse model of myocardial stunning.
AB  - Intracellular calcium (Cai2+) and left ventricular (LV) function were determined
      in the coronary-perfused mouse heart to study Cai2+-related mechanisms of injury
      from myocardial ischemia and reperfusion. Specifics for loading of the
      photoprotein aequorin into isovolumically contracting mouse hearts under constant
      flow conditions are provided. The method allows detection of changes in Cai2+ on
      a beat-to-beat basis in a model of myocardial stunning and permits correlation of
      interventions that regulate Ca2+ exchange with functional alterations. Twenty
      three coronary-perfused mouse hearts were subjected to 15 min of ischemia
      followed by 20 min of reperfusion. In 13 hearts, the perfusate included the
      calmodulin antagonist W7 (10 microM) to inhibit Ca(2+)-calmodulin-regulated
      mechanisms. Peak Cai2+ was 0.77 +/- 0.03 microM in the control group and was
      unaffected by W7 at baseline. Ischemia was characterized by a rapid decline in LV
      function, followed by ischemic contracture, accompanied by a gradual rise in
      Cai2+. Reperfusion was characterized by an initial burst of Cai2+ and a gradual
      recovery to nearly normal systolic Cai2+ while LV pressure recovered to 55% after
      20 min of reperfusion (stunned myocardium). These results in the mouse heart
      confirm that stunning does not result from deficiency of Cai2+ but rather from a
      decreased myofilament responsiveness to Cai2+ due to changes in the myofilaments
      themselves. In hearts perfused with W7, the rise in Cai2+ during ischemia was
      significantly attenuated, as was the magnitude of mean Cai2+ during early reflow.
      Ischemic contracture was abolished or delayed. Hearts perfused with W7 showed
      significantly improved recovery of LV pressure, rate of contraction, and rate of
      relaxation. Diastolic Cai2+ was increased in control hearts during stunning but
      returned to baseline in hearts perfused with W7. Simultaneous assessment of Cai2+
      and LV function demonstrates that calmodulin-regulated mechanisms may contribute
      to the pathogenesis of myocardial stunning in the mouse heart.

PMID- 9612396
TI  - End-systolic stress-velocity and pressure-dimension relationships by
      transthoracic echocardiography in mice.
AB  - The purposes of this study were to assess load-independent, end-systolic
      relationships in mice and compare these relationships to ejection phase indexes
      in assessing contractility. In 13 mice, ejection phase indexes (shortening
      fraction and velocity of fiber shortening) and end-systolic relationships
      [pressure-dimension relationship (ESPDR) and stress-velocity relationship
      (ESSVR)] were determined using M-mode echocardiography and simultaneous left
      ventricular pressure. Load was altered with phenylephrine and nitroprusside.
      Contractility was increased with dobutamine and decreased by induction of
      hypothyroidism. Ejection phase indexes increased with dobutamine infusion but
      were not significantly decreased with hypothyroidism. However, end-systolic
      relationships changed significantly with both dobutamine (gamma-intercepts: ESPDR
      from 22 to 48 mmHg, ESSVR from 3.7 to 6.6 circ/s, P < 0.05) and hypothyroidism
      (gamma-intercepts: ESPDR from 22 to 11 mmHg, ESSVR from 3.7 to 3.2 circ/s, P <
      0.05). We conclude that end-systolic indexes can be accurately measured in the
      intact mouse by echocardiography with simultaneous left ventricular pressure
      recording and appear to be more sensitive to inotropic state than ejection phase
      indexes.

PMID- 9612397
TI  - Apolipoprotein AIV: a potent endogenous inhibitor of lipid oxidation.
AB  - Overexpression of apolipoprotein (apo) AIV in transgenic mice confers significant
      protection against atherosclerosis in apoE knockout animals even in the presence
      of a more severe atherogenic lipid profile. Because lipoprotein oxidation has
      been recognized to be pivotal in development of atherosclerosis, the
      antioxidative activity of apoAIV was investigated. Fasting intestinal lymph was
      used to mimic conditions in the interstitial fluid, the potential site for
      lipoprotein oxidation in vivo. ApoAIV (10 micrograms/ml) significantly inhibited
      copper-mediated oxidation of lymph. This inhibitory effect was further evaluated
      using purified low-density lipoprotein. Addition of apoAIV (2.5 micrograms/ml)
      increased the time of 50% conjugated diene formation by 2.4-fold, whereas apoE or
      BSA did not show such a protection even at 20 micrograms/ml. Addition of apoAIV
      during the propagation phase also resulted in a dose-dependent inhibition. ApoAIV
      also protected macrophage-induced oxidation of fasting lymph. These results
      provide the first evidence that apoAIV is a potent endogenous antioxidant.

PMID- 9612398
TI  - Interaction between carotid baroreflex and exercise pressor reflex depends on
      baroreceptor afferent input.
AB  - Because arterial baroreceptor and skeletal muscle receptor afferents project to
      cardiovascular regions in the lower brain stem such as the nucleus tractus
      solitarii (NTS), it is likely that the level of baroreceptor afferent input will
      modify the excitatory cardiovascular responses evoked by contraction-sensitive
      skeletal muscle afferents. The purpose of this study was to determine the effect
      of carotid sinus baroreceptor afferent input (CSA) on reflex heart rate (HR) and
      mean arterial pressure (MAP) responses evoked by activation of skeletal muscle
      receptor afferents (SMA). CSA input was servo controlled at three levels of
      carotid sinus pressure using the isolated carotid sinus preparation, and SMA
      input was varied by induced muscle contraction (L7-S1 ventral root stimulation)
      or passive muscle stretch. Experiments were performed in alpha-chloralose
      anesthetized and vagotomized dogs (n = 9). When CSA input was low (106 +/- 35
      mmHg), electrically induced muscle contraction increased HR and MAP (30 +/- 8
      beats/min and 42 +/- 12 mmHg, respectively, P < 0.05). However, when CSA input
      was high (221 +/- 9 mmHg), the reflex changes in HR and MAP during muscle
      contraction were attenuated (6 +/- 4 beats/min and 18 +/- 4 mmHg, respectively, P
      < 0.05). Similarly, the sympathoexcitatory responses evoked by passive muscle
      stretch were attenuated in a baroreceptor-dependent manner. These results suggest
      that changing CSA input from low (106 mmHg) to high (221 mmHg) shifts the
      interaction from facilitation to inhibition. Therefore, it is concluded that the
      nature of the interaction (i.e., facilitation or inhibition) between the
      baroreflex and the exercise pressor reflex is dependent on the level of
      baroreceptor input. Moreover, our findings substantiate early studies showing
      that the level of afferent input from arterial baroreceptors is a powerful
      modulator of sympatho-excitation evoked by mechanically and metabolically
      sensitive skeletal muscle receptors.

PMID- 9612399
TI  - NO modulates fetoplacental blood flow distribution and whole body oxygen
      extraction in fetal sheep.
AB  - It is unknown if nitric oxide (NO) influences the relative level of the left (LV)
      and right ventricular (RV) outputs, the blood flow distribution between the body
      and placenta, or whole body O2 extraction and O2 consumption in the fetus. To
      address these questions eight fetal lambs were chronically instrumented at 128
      134 days gestation (term 147 days), and blood flows were measured with
      radioactive microspheres 3-4 days later at baseline and after inhibition of NO
      synthesis with N omega-nitro-L-arginine (L-NNA, 10 and 25 mg/kg i.v.). L-NNA
      progressively reduced the combined ventricular output (P < 0.005) but did not
      alter the relative levels of the LV and RV outputs. Fetal body blood flow fell by
      31% after 10 mg/kg L-NNA (P < 0.005), but a reduction in placental blood flow (P
      < 0.005) was smaller (20%) and not observed until 25 mg/kg L-NNA. Whole body O2
      extraction increased by 71% after 10 mg/kg L-NNA (P < 0.005) and did change
      further at 25 mg/kg L-NNA, whereas whole body O2 consumption rose by 15% at 10
      mg/kg L-NNA (P < 0.05) and returned to baseline at 25 mg/kg L-NNA. These results
      suggest that, as well as reducing the combined ventricular output, inhibition of
      fetal NO synthesis redistributes systemic blood flow toward the placenta and
      increases fetal body O2 extraction. The latter initially increases whole body O2
      consumption and then maintains it at near baseline levels after a fall in
      placental perfusion.

PMID- 9612400
TI  - Hypothalamic-pituitary-adrenal axis changes allow seasonal modulation of
      corticosterone in a bird.
AB  - We examined possible mechanisms underlying seasonal stress modulation in Lapland
      longspurs (Calcarius lapponicus), a species that breeds and molts (the
      energetically costly replacement of feathers) in the Alaskan Arctic. Free-living
      Lapland longspurs show dramatically reduced maximal corticosterone release during
      molt compared with the breeding season, an effect lost in captive birds. Neither
      changes in corticosterone binding proteins nor the overall condition of the bird
      (assessed by weight and fat storage) can explain different seasonal
      corticosterone responses. Adrenal insensitivity also does not fully explain
      reduced maximal output because exogenous ACTH enhanced corticosterone release
      during molt. Exogenous ACTH in molting birds, however, cannot stimulate
      corticosterone to stress-induced levels during breeding, implying reduced adrenal
      capacity. Lapland longspur pituitaries appeared to respond to exogenous
      corticotropin-releasing factor, arginine vasotocin, and mesotocin (the avian
      equivalents of arginine vasopressin and oxytocin) during molt, suggesting that a
      mechanism upstream of the pituitary blunts corticosterone release. Taken
      together, these results indicate that seasonal modulation of corticosterone
      release in this species is controlled at multiple sites in the hypothalamic
      pituitary-adrenal axis.

PMID- 9612401
TI  - Fos expression following isotonic volume expansion of the unanesthetized male
      rat.
AB  - Cardiopulmonary afferents, baroreceptor afferents, or atrial natriuretic peptide
      binding to circumventricular organs may mediate the central response to volume
      expansion, a condition common to pregnancy, exercise training, and congestive
      heart failure. This study used Fos immunocytochemistry to examine brain regions
      activated by volume expansion. Male Sprague-Dawley rats were infused with
      isotonic saline equal to 10% of their body weight in 10 min followed by a
      maintenance infusion of 0.5 ml/min for 110 min. Control animals received 2-h
      infusions at 0.01 ml/min. Five minutes after the start of volume expansion,
      central venous pressure of expanded animals was significantly greater than
      control animals. The volume-expanded group exhibited significantly greater Fos
      activation (P < 0.05) in the area postrema, nucleus of the solitary tract, caudal
      ventrolateral medulla, paraventricular nucleus, supraoptic nucleus, and
      perinuclear zone of the supraoptic nucleus. Double labeling indicates that
      oxytocinergic neurons in the supraoptic nucleus are activated. Neurons in brain
      regions known to inhibit both sympathetic activity and vasopressin release show
      increased Fos expression following isotonic volume expansion.

PMID- 9612402
TI  - Thromboxane A2 acts on the brain to mediate hemodynamic, adrenocorticotropin, and
      cortisol responses.
AB  - Conditions that increase the formation of thromboxane A2 (TxA2) also result in
      activation of hemodynamic and adrenocortical responses. The purpose of this study
      was to test the hypothesis that TxA2 acts directly on the brain to mediate these
      responses. Adult sheep were chronically instrumented with vascular and
      intracerebroventricular catheters. The TxA2 analog U-46619 (0, 100, or 1,000
      ng.kg-1.min-1) and artificial cerebrospinal fluid (CSF) were infused
      intracerebroventricularly for 30 min. Heart rate increased in response to 100
      ng.kg-1.min-1 U-46619 infusions. Heart rate did not change over preinfusion
      values in response to the highest infusion rate, but values were elevated
      compared with the postinfusion period. Mean arterial pressure, ACTH, cortisol,
      hematocrit, and arterial pH (pHa) increased, and arterial partial CO2 pressure
      (PaCO2) fell in response to 1,000 ng.kg-1.min-1 infusions of U-46619. Plasma
      vasopressin concentrations and arterial partial O2 pressure did not change. In a
      second study, U-46619 or artificial CSF was infused intracerebroventricularly
      during prostaglandin synthase blockade. Blockade reduced but did not prevent
      blood pressure responses to U-46619 infusion, suggesting that the U-46619
      infusions increased prostaglandin synthase metabolism to contribute de novo TxA2
      or a second metabolite to augment the blood pressure response. Heart rate, pHa,
      PaCO2, ACTH, and cortisol responses to U-46619 were not different with blockade.
      We conclude that TxA2 acts on the brain to mediate blood pressure, heart rate,
      pHa, PaCO2, hematocrit, ACTH, and cortisol responses. These findings support the
      hypothesis that TxA2 acts directly on the brain to promote cardiovascular and
      hormonal responses that may serve a protective function during conditions when
      TxA2 formation is increased.

PMID- 9612403
TI  - K(+)-neutral amino acid symport of Bombyx mori larval midgut: a system operative
      in extreme conditions.
AB  - The K(+)-dependent symporter for leucine and other neutral amino acids expressed
      along the midgut of the silkworm Bombyx mori operates with best efficiency in the
      presence of a steep pH gradient across the brush-border membrane, with external
      alkaline pH values up to 11, and an electrical potential difference (delta psi)
      of approximately 200 mV. Careful determinations of leucine kinetics as a function
      of external amino acid concentrations between 50 and 1,000 microM, performed with
      brush-border membrane vesicles (BBMV) obtained from the middle and posterior
      midgut regions, revealed that the kinetic parameter affected by the presence of a
      delta pH was the maximal rate of transport. The addition of delta psi caused a
      further marked increase of the translocation rate. At nonsaturating leucine
      concentrations in the solution bathing the external side of the brush-border
      membrane, leucine accumulation within BBMV and midgut cells was not only driven
      by the gradient of the driver cation K+ and delta psi but occurred also in the
      absence of K+. The ability of the symporter to translocate the substrate in its
      binary form allows the intracellular accumulation of leucine in the absence of
      K+, provided that a pH gradient, with alkaline outside, is present. The
      mechanisms involved in this accumulation are discussed.

PMID- 9612404
TI  - Evidence for a low-affinity, high-capacity uniport for amino acids in Bombyx mori
      larval midgut.
AB  - We investigated the kinetics of leucine influx as a function of external
      substrate concentration between 0.03 and 16 mM in brush-border membrane vesicles
      (BBMV) prepared from the middle region of Bombyx mori larval midgut. A detailed
      kinetic analysis of leucine uptake led to the identification, in parallel with
      the K(+)-dependent symporter for neutral amino acids, of a K(+)-independent, low
      affinity, high-capacity system. The parameter values of the Michaelis constant
      (7.12 mM) and maximal rate of transport (4.48 nmol.7 s-1.mg protein-1) were not
      influenced by an external alkaline pH nor by a transmembrane electrical potential
      difference. The uniporter is poorly specific, as it displayed the following rank
      of preference: Leu, His, Val, Ile, Phe, Ser > Lys, Arg, Gln > Pro, 2-amino-2
      norbornane-carboxylic acid, Ala, Gly. The kinetic analysis performed in BBMV
      prepared from the posterior midgut portion indicates that the low-affinity, high
      capacity uniporter is present along the entire length of the silkworm larval
      midgut with similar expression and functional properties.

PMID- 9612405
TI  - Mitochondrial oxidative phosphorylation thermodynamic efficiencies reflect
      physiological organ roles.
AB  - Mitochondria cannot maximize energy production, efficiency, and the cellular ATP
      phosphorylation potential all at the same time. The theoretical and observed
      determinations of coupling of oxidative phosphorylation in mitochondria from rat
      liver, heart, and brain were compared using classical and nonequilibrium
      thermodynamic measures. Additionally, the optimal thermodynamic efficiency and
      flow ratios were determined for control of the two energy-converting complexes of
      the respiratory chain: complex I (NADH), which reflects the integrated cellular
      pathway, and complex II (FADH2), the predominantly tricarboxylic acid (TCA) cycle
      pathway. For all three organs, the cellular respiratory pathway was more tightly
      coupled than the TCA pathway and resulted in a greater optimal efficiency. Liver
      mitochondria are the most thermodynamically efficient at ATP production using
      oxidative phosphorylation. Heart and brain mitochondrial systems utilize more
      oxygen, but can produce ATP at a faster rate than liver systems. Per the theory
      of economic degrees of coupling, isolated rat liver mitochondrial systems are
      designed for the economic production of ATP for use in cellular processes. In the
      brain, the mitochondrial TCA cycle pathway promotes the maximal maintenance of
      the cellular energy state for cellular viability, whereas in the heart the TCA
      cycle pathway maximizes the production of ATP. The coupling of oxidative
      phosphorylation not only can be expected to change with substrate availability
      but may also reflect an ontogenetic response of mitochondria to fit specific
      organ roles in the rat.

PMID- 9612406
TI  - Regulation of skeletal muscle carbohydrate oxidation during steady-state
      contraction.
AB  - Pyruvate dehydrogenase complex (PDC) activation status has been described as
      being central in the regulation of tissue substrate oxidation as outlined by the
      glucose fatty-acid cycle. In the present study we examined the effects of reduced
      lipolysis, with use of nicotinate, and increased PDC activation, with use of
      dichloroacetate (DCA), on substrate utilization during 20 min of submaximal
      steady-state contraction (approximately 80% of maximal O2 uptake) in canine
      gracilis skeletal muscle. At rest, PDC activation was unchanged by nicotinate but
      was approximately 2.5-fold higher in the DCA group than in the control group (P <
      0.05). During contraction, PDC activation status increased to 3.5 mmol acetyl
      CoA.min-1.kg-1 at 37 degrees C in the control group, remained at 4.5 mmol acetyl
      CoA.min-1.kg-1 at 37 degrees C in the DCA group, but only increased to 2.2 mmol
      acetyl-CoA.min-1.kg-1 at 37 degrees C in the nicotinate group (P < 0.05).
      However, the estimated amount of carbohydrate oxidized during the 20-min
      contraction was similar across groups and did not follow the degree of PDC
      activation (81.2 +/- 22.9, 95.9 +/- 11.7, and 89.3 +/- 18.9 mmol glucosyl
      units/kg dry muscle for control, nicotinate, and DCA, respectively). Thus it
      would appear that, during steady-state contraction, PDC activation status does
      not determine the rate of carbohydrate oxidation in skeletal muscle.

PMID- 9612407
TI  - Cholecystokinin satiety involves CCKA receptors perfused by the superior
      pancreaticoduodenal artery.
AB  - Three experiments compared the potency of the type A cholecystokinin (CCKA)
      receptor antagonist devazepide for increasing intake of 30% sucrose when injected
      into the superior pancreaticoduodenal (SPD) artery (SPD group) or jugular vein
      (IV group). In experiment 1, 15 min of sucrose intake in adult, male Sprague
      Dawley rats after 6 h of food deprivation was increased by devazepide (20
      micrograms/kg) administered into the SPD artery whether given alone or in
      conjunction with cholecystokinin octapeptide (CCK-8, 2 micrograms/kg ip).
      Devazepide had no effect in the IV group. In experiment 2, injection of 8, 20,
      and 50 micrograms/kg of devazepide into the SPD artery increased sucrose intake
      of nondeprived rats. Only the highest dose was effective in the IV group. On
      subsequent tests, administration of 1 microgram/kg of CCK-8 significantly
      suppressed intake only in the SPD group. In experiment 3, nondeprived rats with
      SPD artery and jugular vein catheters were tested in a within-subjects design.
      Devazepide (20 micrograms/kg) increased sucrose intake after injection into the
      SPD artery, but not into the jugular vein. In experiment 4, intraduodenal
      devazepide (8, 20, and 50 micrograms/kg) had no effect. These results indicate
      that CCKA receptors within the SPD arterial bed mediate the satiating action of
      CCK, consistent with local action of duodenal CCK.

PMID- 9612408
TI  - Attenuated baroreflex control of sympathetic nerve activity after cardiovascular
      deconditioning in rats.
AB  - The effect of cardiovascular deconditioning on baroreflex control of the
      sympathetic nervous system was evaluated after 14 days of hindlimb unloading (HU)
      or the control condition. Rats were chronically instrumented with catheters and
      sympathetic nerve recording electrodes for measurement of mean arterial pressure
      (MAP) and heart rate (HR) and recording of lumbar (LSNA) or renal (RSNA)
      sympathetic nerve activity. Experiments were conducted 24 h after surgery, with
      the animals in a normal posture. Baroreflex function was assessed using a
      logistic function that related HR and LSNA or RSNA to MAP during infusion of
      phenylephrine and nitroprusside. Baroreflex influence on HR was not affected by
      HU. Maximum baroreflex-elicited LSNA was significantly reduced in HU rats (204 +/
      11.9 vs. 342 +/- 30.6% baseline LSNA), as was maximum reflex gain (-4.0 +/- 0.6
      vs. -7.8 +/- 1.3 %LSNA/mmHg). Maximum baroreflex-elicited RSNA (259 +/- 10.8 vs.
      453 +/- 28.0% baseline RSNA), minimum baroreflex-elicited RSNA (-2 +/- 2.8 vs. 13
      +/- 4.5% baseline RSNA), and maximum gain (-5.8 +/- 0.5 vs. -13.6 +/- 3.1
      %RSNA/mmHg) were significantly decreased in HU rats. Results demonstrate that
      baroreflex modulation of sympathetic nervous system activity is attenuated after
      cardiovascular deconditioning in rodents. Data suggest that alterations in the
      arterial baroreflex may contribute to orthostatic intolerance after a period of
      bedrest or spaceflight in humans.

PMID- 9612409
TI  - A novel mechanism for vasoconstrictor action of 8-isoprostaglandin F2 alpha on
      retinal vessels.
AB  - Using a video-imaging technique, we characterized the effects of 8
      isoprostaglandin F2 alpha (8-iso-PGF2 alpha) on retinal vasculature from piglets.
      8-Iso-PGF2 alpha potently contracted (EC50 = 5.9 +/- 0.5 nM) retinal vessels.
      These effects were completely antagonized by the cyclooxygenase inhibitor
      indomethacin, the thromboxane synthase blocker CGS-12970, the thromboxane
      receptor antagonist L-670596, and the putative inhibitor of the non-voltage
      dependent receptor-operated Ca2+ pathway SKF-96365; constrictor effects of 8-iso
      PGF2 alpha were also partly attenuated by the ETA-receptor blocker BQ-123 and an
      inhibitor of endothelin-converting enzyme, phosphoramidon, but was negligibly
      affected by the L-type voltage-gated Ca2+ channel blocker nifedipine.
      Correspondingly, 8-iso-PGF2 alpha elicited endothelin release from retinal
      preparations, which was markedly reduced by SKF-96365. 8-Iso-PGF2 alpha also
      increased thromboxane production in the retina and cultured endothelial cells,
      but not on retinovascular smooth muscle cells; these effects of 8-iso-PGF2 alpha
      were blocked by indomethacin, CGS-12970, SKF-96365, and EGTA, but not by
      nifedipine. 8-Iso-PGF2 alpha also increased Ca2+ transients in retinal
      endothelial cells, which were inhibited by SKF-96365 and EGTA, but not by
      nifedipine, whereas in smooth muscle cells U-46619, but not 8-iso-PGF2 alpha,
      stimulated a rise in Ca2+ transients. Finally, H2O2 + FeCl2 (in vitro) and anoxia
      followed by reoxygenation (in vivo) stimulated formation of 8-iso-PGF2 alpha in
      the retina. In conclusion, 8-iso-PGF2 alpha-induced retinal vasoconstriction is
      mediated by cyclooxygenase-generated formation of thromboxane and, to a lesser
      extent, by endothelin after Ca2+ entry into cells, possibly through receptor
      operated channels. Retinal vasoconstriction to 8-isoprostanes might play a role
      in the genesis of ischemic retinopathies.

PMID- 9612410
TI  - Role of the insular cortex in the modulation of baroreflex sensitivity.
AB  - Cervical vagal stimulation for 2 h results in a depressed baroreflex sensitivity
      produced by an enhanced sympathetic output, as indicated by increased plasma
      norepinephrine levels. The current study examined the role of the insular cortex
      in modulating the vagal stimulation-induced changes in baroreflex sensitivity.
      Male Sprague-Dawley rats were anesthetized with thiobutabarbitol sodium and
      instrumented for recording blood pressure, heart rate, intravenous drug
      administration, and vagal afferent nerve stimulation. Stereotaxic microinjections
      (300 nl) of either 5% lidocaine or 0.9% saline were made bilaterally into the
      insula. Thirty minutes after 2 h of vagal stimulation, the baroreflex was
      significantly depressed and plasma norepinephrine levels were significantly
      elevated in both groups. The baroreflex was also significantly depressed after
      bilateral lidocaine injections into the insula, independent of vagal stimulation.
      However, no significant change in plasma norepinephrine was observed, suggesting
      that an attenuated parasympathetic output contributed to the altered baroreflex.
      Taken together, the results suggest that the insular cortex modulates the cardiac
      baroreflex through a modulation of parasympathetic output.

PMID- 9612411
TI  - Vagovagal reflex motility patterns of the rat esophagus.
AB  - Esophageal reflex motility and its neural correlates were investigated in 94
      urethan-anesthetized adult male albino rats. When distended by means of a
      stationary balloon, the cervical and thoracic esophageal portion responded with a
      single pressure wave (type I response), whereas the diaphragmatic (intercrural)
      segment exhibited rhythmic contractions (type II response). Balloon deflation
      resulted in an off response aboral to the balloon. Bilateral cervical vagotomy or
      systemic D-tubocurarine abolished all types of reflex responses. Both type I and
      type II responses were associated with multiunit discharges in the central
      subnucleus of the solitary tract complex (NTSC) and the compact formation of the
      nucleus ambiguus (AMBC). Type I discharges, consisting of single bursts, and type
      II discharges, consisting of rhythmic 0.6-Hz bursts, preceded intraesophageal
      pressure waves in a fixed phase relationship, persisted after contralateral
      vagotomy, and were eliminated by ipsilateral vagotomy. During neuromuscular
      paralysis, peak intraburst discharge rates were reduced in both the NTSC and
      AMBC, with a concomitant decrease in rhythmicity. It is concluded that
      bolusevoked peristalsis of the rat esophagus is 1) segmentally organized; 2)
      effected by a bilateral uncrossed reflex arc consisting of vagal viscerosensory,
      NTSC premotor, and AMBC motoneurons innervating the striated muscle tunic and 3)
      strongly facilitated by reafferent feedback.

PMID- 9612412
TI  - Vagal afferent transmission in the NTS mediating reflex responses of the rat
      esophagus.
AB  - In urethan-anesthetized rats, esophageal distension evoked volume-dependent
      reflex contractions with phase-locked multiunit discharges in the central
      subnucleus of the solitary tract complex (NTSC) and the nucleus ambiguus. During
      blockade of solitarial, but not peripheral, muscarinic cholinoceptors, the volume
      response relationship of reflex contractions was shifted rightward with a
      depression in pressure wave amplitude. Concurrently, premotor NTSC responses were
      attenuated and nucleus ambiguus activity was abolished during esophagomotor
      inhibition. Both NTSC discharges and reflex responses were eliminated, or
      strongly inhibited, during blockade of excitatory amino acid receptors (EAARs)
      with 6-cyano-7-nitroquinoxaline-2,3-dione, gamma-glutamylglycine or 2-amino-7
      phosphonoheptanoate. In brain stem slice preparations, whole cell recordings in
      the NTSC region revealed fast excitatory postsynaptic potentials (EPSPS) with
      spikes in response to electrical stimulation of the solitary tract. Although
      spiking was facilitated by muscarine, EPSPS were resistant to cholinoceptor
      antagonists but sensitive to EAAR blockers. We conclude that esophageal vagal
      afferents excite ipsilateral NTSC interneurons via activation of glutamate
      receptors of the DL-alpha-amino-3-hydroxy-5-methylisoxazole-propionic acid and N
      methyl-D-aspartate subtypes. Cholinergic input to the NTSC probably derives from
      propriobulbar sources and serves to modulate the responsiveness of reflex
      interneurons.

PMID- 9612413
TI  - Sphingomyelinase has an insulin-like effect on glucose transporter translocation
      in adipocytes.
AB  - Rat epididymal adipocytes were incubated with 0, 0.1, and 1 mU
      sphingomyelinase/ml for 30 or 60 min, and glucose uptake and GLUT-1 and GLUT-4
      translocation were assessed. Adipocytes exposed to 1 mU sphingomyelinase/ml
      exhibited a 173% increase in glucose uptake. Sphingomyelinase had no effect on
      the abundance of GLUT-1 in the plasma membrane of adipocytes. In contrast, 1 mU
      sphingomyelinase/ml increased plasma membrane content of GLUT-4 by 120% and
      produced a simultaneous decrease in GLUT-4 abundance in the low-density
      microsomal fraction. Sphingomyelinase had no effect on tyrosine phosphorylation
      of either the insulin receptor beta-subunit or the insulin receptor substrate-1,
      a signaling molecule in the insulin signaling pathway. It is concluded that the
      incubation of adipocytes with sphingomyelinase results in insulin-like
      translocation of GLUT-4 to the plasma membrane and that this translocation does
      not occur via the activation of the initial components of the insulin signaling
      pathway.

PMID- 9612414
TI  - Exercise effects on lung tumor metastases and in vitro alveolar macrophage
      antitumor cytotoxicity.
AB  - This study examined the effects of moderate and prolonged exercise on 1) lung
      tumor metastases and 2) alveolar macrophage antitumor response in vitro. C57B1/6
      mice were assigned to either Ex-30 (30-min run), Ex-F (run to fatigue), Ex-F-24 h
      (run to fatigue 24 h before tumor injection), or Con (rested in lanes above the
      treadmill). Mice received intravenous injections of syngeneic B16 melanoma cells
      30 min postexercise. Lungs were removed 7 or 10 days later, and tumor foci were
      counted. Ex-F had fewer tumors than either Ex-30 or Con, whereas Ex-F-24 h also
      showed a strong trend toward fewer tumors. The initial localization of tumor
      cells in the lungs after injection was not different among groups. For the in
      vitro experiment, mice were killed immediately after exercise or 8 h later.
      Alveolar macrophages were removed and cultured in vitro with B16 melanoma cells.
      The growth of the tumors cultured with macrophages from Ex-F was lower than Con
      after exercise and, to a lesser extent, 8 h later. In Ex-30, this effect was only
      found immediately after exercise. The data suggest that prolonged exercise has a
      protective effect on lung tumor metastases and enhances alveolar macrophage
      antitumor cytotoxicity.

PMID- 9612415
TI  - Qualitative regional differences in adipose tissue growth and cellularity in male
      Wistar rats fed ad libitum.
AB  - Adipose tissue grows primarily by a combination of increases in fat cell volume
      (hypertrophy) and in fat cell number (hyperplasia), but the regional growth
      pattern of white adipose tissue depots in animal species and in the human is
      still unclear. In this study we characterized fully the age-related changes in
      adipose tissue growth, composition, and cellularity of four fat depots of male
      Wistar rats that varied in age from 7 wk to 15 mo and in body weight from 178 to
      808 g. Body weight and the weight of each of the four adipose depots studied
      (epididymal, mesenteric, subcutaneous inguinal, and retroperitoneal) increased
      progressively with age and ad libitum feeding. Comparison of the cellularity of
      the four adipose depots, however, showed remarkable and significant differences
      in the pattern of growth within the same animals. The cumulative growth of the
      two intraabdominal fat depots (mesenteric and epididymal) was due mostly to
      hypertrophy (increases in cell volume of 83 and 64%, respectively), whereas the
      growth of the other two depots (retroperitoneal and inguinal) was due
      predominantly to hyperplasia (increases in cell number of 58- and 65%,
      respectively). These findings uncover major and unexpected regional differences
      in the modulation of adipose tissue growth within aging animals fed ad libitum
      and suggest local, region-specific regulatory controls of this growth.

PMID- 9612416
TI  - Neurophysiological modeling of voiding in rats: urethral nerve response to
      urethral pressure and flow.
AB  - In male urethan-anesthetized rats, activity was measured in nerves that run over
      the proximal urethra. The urethral nerve response to stepwise urethral perfusion
      could be described by a four-parameter model (fit error < 6%). At the onset of
      perfusion, the urethra was closed and the pressure increased with the infused
      volume. The nerve activity (NA) increased linearly with this inserted volume to a
      maximum (NAmax), which was proportional to the instantaneous pressure. The
      duration of this first episode (delta t) was inversely proportional to the
      perfusion rate. After infusion of a fixed volume, the urethra opened and the NA
      decreased with a time constant phi -1 (approximately 1.8 s) to an elevated level
      (NAlevel). NAlevel was linearly related to the steady-state pressure.
      Accordingly, sensors in the urethra are sensitive to pressure rather than to the
      perfusion rate. The parameters NAmax, NAlevel, and delta t showed very good
      reproducibility (SD approximately 19% of mean). The measured activity was most
      likely afferent and conducted to the major pelvic ganglion.

PMID- 9612417
TI  - Marked and rapid decreases of circulating leptin in streptozotocin diabetic rats:
      reversal by insulin.
AB  - Evidence for regulation of circulating leptin by insulin is conflicting. Diabetes
      was induced in rats with streptozotocin (STZ; 40 mg.kg(-1).day(-1) x 2 days) to
      examine the effect of insulin-deficient diabetes and insulin treatment on
      circulating leptin. After 12 wk, plasma leptin concentrations in untreated rats
      were all < 0.4 ng/ml versus 4.9 +/- 0.9 ng/ml in control animals (P < 0.005). In
      rats treated with subcutaneous insulin implants for 12 wk, which reduced
      hyperglycemia by approximately 50%, plasma leptin was 2.1 +/- 0.6 ng/ml, whereas
      leptin concentrations were 6.0 +/- 1.6 ng/ml in insulin-implanted rats receiving
      supplemental injections of insulin for 4 days to normalize plasma glucose (P <
      0.005 vs. STZ untreated). In a second experiment, plasma leptin was monitored at
      biweekly intervals during 12 wk of diabetes. In rats treated with insulin
      implants, plasma leptin concentrations were inversely proportional to glycemia (r
      = -0.64; P < 0.0001) and unrelated to body weight (P = 0.40). In a third
      experiment, plasma leptin concentrations were examined very early after the
      induction of diabetes. Within 24 h after STZ injection, plasma insulin decreased
      from 480 +/- 30 to 130 +/- 10 pM (P < 0.0001), plasma glucose increased from 7.0
      +/- 0.2 to 24.8 +/- 0.5 mM, and plasma leptin decreased from 3.2 +/- 0.2 to 1.2
      +/- 0.1 ng/ml (delta = -63 +/- 3%, P < 0.0001). In a subset of diabetic rats
      treated with insulin for 2 days, glucose decreased to 11.7 +/- 3.9 mM and leptin
      increased from 0.5 +/- 0.1 to 2.9 +/- 0.6 ng/ml (P < 0.01) without an effect on
      epididymal fat weight. The change of leptin was correlated with the degree of
      glucose lowering (r = 0.75, P < 0.05). Thus insulin-deficient diabetes produces
      rapid and sustained decreases of leptin that are not solely dependent on weight
      loss, whereas insulin treatment reverses the hypoleptinemia. We hypothesize that
      decreased glucose transport into adipose tissue may contribute to decreased
      leptin production in insulin-deficient diabetes.

PMID- 9612418
TI  - Electrical potential difference between exocelomic fluid and maternal blood in
      early pregnancy.
AB  - The forces that drive transfer of solutes between maternal blood and embryo in
      early human pregnancy are poorly understood. The aim of this study was to
      determine whether there is an electrical potential difference (PD) between
      maternal blood and the exocelomic cavity and between maternal blood and the
      amniotic cavity in the normal human conceptus at or before 10 wk of pregnancy. We
      measured PD between a saline-filled catheter in a forearm vein of women
      undergoing termination of pregnancy for psychological reasons in the first
      trimester and a second saline-filled catheter in the exocelomic cavity or
      amniotic cavity of their conceptus. The mean (+/- SE) maternal blood/exocelomic
      cavity PD in eight women was 8.7 +/- 1.0 mV and the mean maternal blood/amniotic
      cavity PD in four of the women was 6.7 +/- 1.3 mV, embryo side negative for both
      sets of measurement. These data show that there is a PD between maternal and
      embryonic extracellular fluid in the first trimester that will directly influence
      exchange of ions between the two compartments.

PMID- 9612419
TI  - Theta values for C16O18O and C18O2 related to respective pulmonary diffusing
      capacities.
AB  - The single-breath diffusing capacities for singly and doubly 18O-labeled CO2,
      DLC16O18O and DLC18O2, as well as for NO, were determined in seven anesthetized
      rabbits to investigate whether the theoretically predicted ratio of specific
      blood uptake rates of both isotopic CO2 species, theta C18O2/theta C16O18O = 2.0,
      can be derived from the measured values of DLC16O18O and DLC18O2. Data of DL were
      obtained by inflating the lungs with gas mixtures containing 0.35% C16O18O or
      0.8% C18O2 or 0.05% NO in nitrogen, with breath-holding periods of 0.05-0.5 s and
      2-12 s for the CO2 and NO tests, respectively. theta C18O2/theta C16O18O was
      calculated by applying the double-reciprocal Roughton-Forster equation to DL
      values obtained in each animal and by assuming that NO diffusing capacity
      represents the gas conductance of the alveolar-capillary membrane. The measured
      ratio was theta C18O2/theta C16O18O = 1.9 +/- 0.2 (mean +/- SD), thus comparing
      reasonably with the predicted one. Therefore, our findings provide evidence that
      the greater value of DLC18O2 is mainly due to the twofold higher probability (or
      theta value) for C18O2 than for C16O18O to disappear within red blood cells via
      isotopic exchange reactions.

PMID- 9612420
TI  - A potent neuropeptide Y antagonist, 1229U91, suppressed spontaneous food intake
      in Zucker fatty rats.
AB  - Neuropeptide Y (NPY) is one of the most potent orexigenic substances known.
      1229U91 was found to be a potent and selective NPY antagonist. To elucidate a
      physiological role of NPY in hyperphagia in obese animals, we studied the effect
      of 1229U91 on spontaneous food intake in obese and lean Zucker rats. The food
      intake of Zucker rats was suppressed by intracerebroventricular administration of
      1229U91 more potently in obese than in lean animals without abnormal behavior
      (31.7 and 67.3% inhibition at doses of 10 and 30 micrograms, respectively, in
      Zucker fatty rats and 22.2% inhibition at 30 micrograms in lean rats). This
      compound markedly suppressed NPY-induced food intake at 30 micrograms but did not
      affect galanin-induced food intake, suggesting that the feeding suppression seen
      in Zucker fatty and lean rats is pharmacologically and behaviorally specific.
      These results suggest that NPY is involved in feeding behavior in Zucker fatty
      rats and that NPY contributes to feeding to a greater degree in Zucker fatty than
      in lean rats. The hyperphagia in Zucker fatty rats may be due to the abnormal
      overactivation of the NPYergic system.

PMID- 9612421
TI  - Central mechanisms for the hypertensive effects of preproadrenomedullin-derived
      peptides in conscious rats.
AB  - Peptides derived from postranslational processing of preproadrenomedullin exert
      potent hypotensive effects in the periphery. One of those peptides,
      adrenomedullin (AM) also has been demonstrated to act centrally in conscious rats
      to inhibit water drinking and salt appetite and, in anesthetized rats,
      surprisingly to increase blood pressure. We examined the effects of AM and the
      other postranslational product, proadrenomedullin NH2-terminal 20 peptide (PAMP),
      on blood pressure in conscious rats. Both AM and PAMP elicited dose-related
      increases in mean arterial pressure after cerebroventricular administration. The
      hypertensive effects of both AM and PAMP and of ANG II were blocked by peripheral
      administration of phentolamine, indicating actions of the peptides in brain to
      stimulate sympathetic nervous system function. Blockade of central ANG II
      receptors with saralasin prevented the hypertensive effects of both ANG II and
      PAMP, suggesting recruitment of endogenous angiotensinergic systems by central
      PAMP. The structural homolog of AM, calcitonin gene-related peptide (CGRP), at
      similar doses did nto significantly affect blood pressure. Furthermore, the
      hypertensive effects of ANG II, AM, and PAMP were not abrogated by prior
      administration of the CGRP antagonist. We hypothesize that AM and PAMP exert
      cardioprotective effects in brain, which may counterbalance the volume-unloading
      actions of the peptides in the periphery.

PMID- 9612422
TI  - Remember why you became a nurse.

PMID- 9612423
TI  - A dangerous combination.

PMID- 9612424
TI  - Anorexia nervosa.

PMID- 9612425
TI  - When can an adolescent give consent?

PMID- 9612427
TI  - Marijuana as a medicine.

PMID- 9612428
TI  - Reporting cases of meningitis.

PMID- 9612429
TI  - "Noncompliant." Isn't there a better way to say it?

PMID- 9612430
TI  - Emergency! Diaphragmatic rupture.

PMID- 9612431
TI  - Clinical snapshot. Infective endocarditis.

PMID- 9612432
TI  - Nurses Week tribute: a nursing call to action.

PMID- 9612433
TI  - Testing feeding tube placement. Auscultation vs. pH method.

PMID- 9612434
TI  - Creating fulfillment in today's workplace. A guide for nurses.

PMID- 9612435
TI  - Preparing patients for early discharge After CABG.

PMID- 9612436
TI  - State nurses associations work to prove nursing quality.

PMID- 9612437
TI  - A brief update on stroke.

PMID- 9612438
TI  - Grief counseling.

PMID- 9612439
TI  - Analgesic use during pregnancy.

PMID- 9612440
TI  - Reporting fraud.

PMID- 9612441
TI  - Nurses' rights equal quality care.

PMID- 9612442
TI  - The coming of age of self-mutilation.
AB  - Self-mutilation (SM), the deliberate, nonsuicidal destruction of one's own body
      tissue, occurs in such culturally sanctioned practices as tattooing; body
      piercing; and healing, spiritual, and order-preserving rituals. As a symptom, it
      has typically been regarded as a manifestation of borderline behavior and
      misidentified as a suicide attempt. It has begun to attract mainstream media
      attention, and many more who suffer from it are expected to seek treatment. This
      review suggests that SM can best be understood as a morbid self-help effort
      providing rapid but temporary relief from feelings of depersonalization, guilt,
      rejection, and boredom as well as hallucinations, sexual preoccupations, and
      chaotic thoughts. Major SM includes infrequent acts such as eye enucleation and
      castration, commonly associated with psychosis and intoxication. Stereotypic SM
      includes such acts as head banging and self-biting most often accompanying
      Tourette's syndrome and severe mental retardation. Superficial/moderate SM
      includes compulsive acts such as trichotillomania and skin picking and such
      episodic acts as skin-cutting and burning, which evolve into an axis I syndrome
      of repetitive impulse dyscontrol with protean symptoms.

PMID- 9612443
TI  - Suicidal children grow up: relations between family psychopathology and
      adolescents' lifetime suicidal behavior.
AB  - Standard family history and family study methods were used with 650 first- and
      1174 second-degree biological relatives of 133 adolescents who were studied
      initially 6 to 8 years ago. They included 69 prepubertal children considered at
      risk for suicidal behavior and 64 prepubertal children selected from the
      community. This study aimed to identify relationships between family
      psychopathology and adolescents' lifetime history of suicidal states. Family
      discord, suicide attempts of mother, and substance abuse of mothers and fathers
      were significantly more prevalent among adolescents with lifetime history of a
      suicide attempt. Mothers' and fathers' substance abuse was associated with
      adolescents' lifetime history of suicidal ideation. Results highlight importance
      of evaluating and treating family psychopathology to reduce risk for youth
      suicidal states.

PMID- 9612444
TI  - HIV-risk behavior and the public health context of HIV/AIDS among women living
      with a severe and persistent mental illness.
AB  - We documented HIV-risk behavior and the public health context of AIDS in women
      living with a severe and persistent mental illness. Sixty-one women were
      recruited from outpatient clinics and day-treatment programs at a state
      psychiatric hospital. They completed a survey that included measures of HIV
      related risk behavior, the perceived importance of 11 public health and social
      problems including AIDS, HIV/AIDS-related knowledge, perceived risk, and
      behavioral intentions. Thirty-eight percent of participants engaged in at least
      one type of HIV-risk behavior during the 2 months before assessment, 23% reported
      two or more risk factors, and 16% reported three or more risk factors. Consistent
      condom use was rare. Participants reporting 1 or more risk factors were more
      likely than those reporting no risk to report histories of alcohol or drug
      treatment, sexually transmitted diseases, HIV testing, and more perceived risk of
      HIV infection. Poverty and unemployment were viewed as more serious problems than
      HIV infection and AIDS. HIV-prevention interventions that are tailored to the
      needs and priorities of women with a severe mental illness are urgently needed to
      prevent further infections.

PMID- 9612445
TI  - Methodological issues in the use of survey questionnaires to assess the health
      effects of torture.
AB  - It has become increasingly important to identify torture survivors among
      subgroups of the American population and to assess the continuing health effects
      of torture experience. To determine whether survey questionnaires can be
      effectively used to make such assessments, we reviewed the recent literature on
      refugee health, on the measurement and treatment of trauma, and in the related
      areas of survey methodology and cognitive psychology. We conclude that, if
      properly conducted, the survey approach represents an effective method, and we
      propose specific recommendations concerning procedures that may be used in
      surveys of torture survivors to maximize study validity.

PMID- 9612446
TI  - Characteristics of recipients of Supplemental Security Income (SSI) benefits for
      drug addicts and alcoholics.
AB  - This study examined symptom severity and level of functioning in recipients of
      Supplemental Security Income (SSI) benefits for drug addicts and alcoholics
      (DA&A). Although substantial numbers of substance abusers received these benefits
      until the program was canceled in 1997, little information has been available on
      the characteristics of these individuals. Approximately 2500 SSI DA&A recipients
      were assessed at the point in which they were to be referred for treatment
      services. Results indicated that in addition to long histories of alcohol abuse
      and recent problems with employment, these DA&A recipients were characterized by
      high levels of medical and psychiatric problems. Problem severities in these
      latter two areas were found to be consistently high across several subgroupings
      of recipients, including those who reported no alcohol or drug use in the prior
      30 days. These findings suggest that SSI DA&A recipients are often significantly
      impaired beyond their alcohol and drug use.

PMID- 9612447
TI  - Contribution of cognitive impairment, depression, and psychosis to the outcome of
      agitated geropsychiatric inpatients with dementia.
AB  - This study investigated the correlates of change in behavioral disturbance in
      geropsychiatric inpatients with dementia. It was hypothesized that improvement in
      specific psychiatric symptoms, such as psychosis and depression, contribute to
      the improvement of specific behavioral disturbances. All admissions between
      October 1993 and May 1995 were reviewed to identify those patients admitted to
      the Houston VA geropsychiatry unit with a diagnosis of dementia; 233 patients
      were included in the study. Improvement in behavioral disturbance symptoms was
      associated with decreases in depression, thought disorder, and hostility.
      However, the relative importance of depressive and psychotic symptoms varied
      depending upon the type of behavioral disturbance examined. These results may
      support a focused approach employing therapies specific to the type of behavioral
      disturbance.

PMID- 9612448
TI  - Use of the Center for Epidemiologic Studies Depression (CES-D) Scale in Korea.
AB  - We translated the Center for Epidemiologic Studies Depression (CES-D) Scale into
      Korean, paying careful attention to culturally different modes of expression of
      depressive feelings and thoughts. The final translated version (CES-D-K) was
      administered to 164 psychiatric patients and 464 normal subjects residing in the
      community. Reliability, validity, and the optimal cutoff point of this scale were
      estimated, including ROC analysis. The CES-D-K was reliable and valid for the
      Korean population. Two optimal cutoff points were suggested: 24/25, the point
      which best corresponded to the clinical diagnosis of depression, and 20/21, which
      most effectively detects and covers depressive symptoms during screening. The
      higher cutoff points than those in Western countries may be due to different ways
      of expression affect, especially the suppression of positive affect, in cultures
      based on Confucian ethics.

PMID- 9612449
TI  - Illness intrusiveness in individuals with panic disorder, obsessive-compulsive
      disorder, or social phobia.
AB  - To measure the extent to which anxiety disorders interfere with various domains
      of functioning, the Illness Intrusiveness Ratings Scale (IIRS) was completed by
      individuals with a DSM-IV principal diagnosis of panic disorder (PD; N = 35),
      obsessive-compulsive disorder (OCD; N = 51), or social phobia (SP; N = 49).
      Although the three groups did not differ on total IIRS scores, group differences
      did emerge for particular domains of functioning. Patients with OCD reported
      significantly more interference with respect to passive recreation (e.g.,
      reading) than did SP patients and with respect to religious expression compared
      with both PD and SP patients. Patients with SP reported more impairment with
      respect to social relationships and self-expression/self-improvement compared
      with the other two groups. When compared with populations with a variety of other
      chronic illnesses, patients in the present study reported much higher levels of
      illness intrusiveness. The implications of these findings and future directions
      for research are discussed.

PMID- 9612450
TI  - Survivors of torture presenting at an anxiety disorders clinic: symptomatology
      and pharmacotherapy.

PMID- 9612451
TI  - Preventing rheumatic heart disease in Australia.

PMID- 9612453
TI  - Homocysteine and vascular disease.

PMID- 9612452
TI  - Problem-based learning: does it prepare medical students to become better
      doctors?

PMID- 9612454
TI  - Asthma and other atopic diseases in Australian children. Australian arm of the
      International Study of Asthma and Allergy in Childhood.
AB  - OBJECTIVE: To determine the prevalence of asthma, eczema and allergic rhinitis in
      Australian schoolchildren using the protocol of the International Study of Asthma
      and Allergy in Childhood (ISAAC). DESIGN: Questionnaire-based survey. SETTING:
      Melbourne, Sydney, Adelaide (in winter-spring, 1993) and Perth (in winter-spring,
      1994). SUBJECTS: All children in school years 1 and 2 (ages 6-7 years) or in year
      8 (ages 13-14 years), attending a random sample of 272 schools, stratified by age
      and city. MAIN OUTCOME MEASURES: Parent-reported (for 6-7 year olds) or self
      reported (for 13-14 year olds) symptoms of atopic disease in the previous 12
      months, or ever; treatment of asthma; and country of birth. RESULTS: 10,914
      questionnaires were completed for 6-7 year olds and 12,280 for 13-14 year olds
      (84% and 94% response rates, respectively). Prevalence of wheeze in the past 12
      months was 24.6% for the 6-7 year olds and 29.4% for the 13-14 year olds, and,
      among 6-7 year olds, was significantly higher in boys (27.4%) than girls (21.7%).
      Children born in Australia were more likely to report current wheeze than those
      born elsewhere (6-7 year olds: odds ratio [OR], 1.82; 95% confidence interval
      [CI] 1.55-2.15; and 13-14 year olds: OR, 1.88; 95% CI, 1.68-2.11). Prevalences of
      current eczema and allergic rhinitis were 10.9% and 12.0%, respectively, for the
      6-7 year olds, and 9.7% and 19.6%, respectively, for the 13-14 year olds. Asthma,
      eczema and rhinitis coexisted in 1.8% of 6-7 year olds and 2.8% of 13-14 year
      olds. CONCLUSION: This study provides evidence that asthma prevalence in
      Australian schoolchildren is continuing to increase and is higher among
      Australian-born children than among those born elsewhere. Asthma, eczema and
      allergic rhinitis coexist to a lesser extent than expected. These results form
      the basis for future Australian and international comparisons.

PMID- 9612455
TI  - Musculoskeletal disability among elderly people in the community.
AB  - OBJECTIVES: To determine the prevalence and determinants of disability among
      elderly people living in the community. DESIGN: A cross-sectional postal
      questionnaire survey. SETTING: Northern Sydney Area Health Service. PARTICIPANTS:
      1527 residents (622 men and 905 women) aged 65 years and over. MAIN OUTCOME
      MEASURES: Self-reported chronic illnesses, injuries or conditions; difficulties
      with activities of daily living assessed by the Health Assessment Questionnaire
      (HAQ); and home modification and use of functional aids. RESULTS: "Arthritis or
      rheumatism" was the leading long term condition, reported by 59.5%, 55.8% and
      59.7% of women and 40.5%, 47.0% and 43.6% of men in the three age groups (65-74,
      75-84 and 85 years and over), respectively. The back, neck and knees were the
      most common sites of pain and stiffness. Of the respondents, 23.4% of women and
      24.3% of men reported regularly taking nonsteroidal anti-inflammatory drugs.
      Impaired performance of activities of daily living increased with age, with
      53.9%, 70.7% and 89.6% of women and 37.6%, 63.6% and 73.2% of men in the
      respective age groups reporting at least some difficulty (HAQ score > 0).
      Multivariate analysis found self-reported poor general health, loss of a limb,
      arthritis or rheumatism, other long term conditions restricting physical
      activity, impaired vision, female sex, and age to be significant predictors of
      disability as measured by HAQ scores. Only 13.9% of women and 9.4% of men had
      made changes to their home. Functional aids were used by 27.7%, 37.3% and 65.9%
      of women and 15.6%, 33.4% and 59.1% of men in the respective age groups.
      CONCLUSION: Arthritis and rheumatism were the most prevalent chronic conditions
      among elderly people in the community, and were significantly associated with
      difficulty with performing activities of daily living, after controlling for
      effects of age, sex and other chronic conditions.

PMID- 9612456
TI  - Septic arthritis of the knee caused by Edwardsiella tarda after a catfish
      puncture wound.
AB  - Anglers are wary of catfish as their sharp fin spines may cause injury and, in
      some species, envenomation. We describe another complication of catfish spine
      injury--septic arthritis caused by Edwardsiella tarda. We believe this is the
      first report of this organism causing septic arthritis.

PMID- 9612457
TI  - Problem-based learning: its rationale and efficacy.
AB  - Problem-based learning (PBL) in medical education uses clinical cases as the
      context for students to study basic and clinical sciences. Its possible
      advantages over traditional approaches include its greater relevance to the
      practice of medicine, its ability to promote retention and application of
      knowledge, and its encouragement of self-directed life-long learning. Possible
      disadvantages include higher costs, both in resources and staff time. Although
      its efficacy is difficult to evaluate, the current enthusiasm for PBL seems
      justified and its use is likely to increase further.

PMID- 9612458
TI  - The death of a healthy volunteer in a human research project: implications for
      Australian clinical research.
AB  - A healthy 19-year-old United States college student volunteer in a clinical
      research program underwent a bronchoscopy and died as a result of acute
      lignocaine toxicity. The major contributing factor in the tragedy was that the
      research protocol failed to specify an upper dose limit for lignocaine spray,
      although previous versions of the protocol had done so. We look at the
      implications of this case for Australian institutional ethics committees.

PMID- 9612459
TI  - Developing visiting surgical services for rural and remote Australian
      communities.
AB  - The University Department of Surgery at Queen Elizabeth II Medical Centre (Perth,
      Western Australia) has undertaken a pilot project to provide surgical services to
      country communities where no such service exists. Three surgeons undertake a
      regular schedule of appointments, and are accompanied by final-year medical
      students to give them experience with common conditions rarely managed in
      teaching hospitals. The service is supported by a central administrative office
      and coordinated by a general practitioner, who negotiates with the regional
      healthcare providers. Patients are referred by their general practitioner, who
      may work with the surgeon as anaesthetist or surgical assistant.

PMID- 9612460
TI  - Eating disorders from a primary care perspective.

PMID- 9612461
TI  - Topical tretinoin and fetal malformations.

PMID- 9612462
TI  - Phytoestrogens and prostate cancer: possible preventive role.

PMID- 9612463
TI  - Undernutrition in elderly patients.

PMID- 9612464
TI  - Beware our "best friend": Capnocytophaga canimorsus septicaemia after a dog bite.

PMID- 9612465
TI  - Medical end-of-life decisions and legislation.

PMID- 9612466
TI  - Lung volume reduction surgery for emphysema.

PMID- 9612467
TI  - Evaluation of new surgical procedures.

PMID- 9612468
TI  - Phaeochromocytoma and hypotension.

PMID- 9612469
TI  - Counting the cost of disrupting the vaccine cold chain.

PMID- 9612470
TI  - Use of a men's group in health promotion in rural areas.

PMID- 9612471
TI  - Choking after inhaling a foreign body through a Ventolin puffer.

PMID- 9612473
TI  - Trends in general practice in the Waikato, 1979-80/1991-92, I: Practitioner
      availability, service use and clinical activity.
AB  - AIMS: To document trends in availability and use of general practitioner services
      and in patterns of clinical activity for the Waikato over the period 1979-80 to
      1991-92. METHODS: The data are drawn from a baseline and a follow-up survey of
      general practice in the Waikato region representing a 1% sample of all in
      surgery, in-hours, week-day encounters at two points in time. The data were
      recorded by participating general practitioners in four collection weeks spaced
      over the period of a year. In total, 9468 and 10,235 patient encounter forms were
      completed. RESULTS: While the number of general practitioners increased by a half
      over the period, average workload declined by a fifth, the inflation-adjusted
      value of the usual adult fee increased by nearly 50% and visits went up by an
      average of a half a visit a year. Clinical activity declined for prescribing but
      increased for referral and follow-up. CONCLUSIONS: The increase in availability
      of general practitioners over the last decade has been associated with
      significant changes in patterns of practice organisation, service utilisation and
      clinical activity. Further research is required into the potential impact of
      greater service availability on patient demand and resource use.

PMID- 9612472
TI  - The management of ischaemic nephropathy.

PMID- 9612474
TI  - Population-based breast cancer screening: policy advice for a New Zealand
      screening programme. Breast Cancer Screening Policy Advisory Group.
AB  - The Ministry of Health appointed the Breast Cancer Screening Policy Advisory
      Group in 1995 to provide policy advice on the establishment of a population-based
      screening programme in New Zealand. The group recommended that an organised
      mammographic screening programme be part of a strategic approach to breast cancer
      detection and management with the aim of reducing mortality from breast cancer.
      Service specifications should be based on those of the pilot programmes in Otago
      Southland and Waikato, but modified according to the lessons learned, with
      special attention to such areas as recruitment and information systems. Women
      between the ages of 50-69 should be invited for screening every two years, and
      screening should be free of charge. Because of the uncertain value of general
      population screening by mammography in women under the age of 50, the programme
      should not be extended to younger women, including those at high risk, at the
      present time. Further reviews of the issue should be commissioned when new
      evidence becomes available. Pilot programmes in New Zealand have demonstrated
      that screening can be performed with acceptable standards in comparison with
      overseas trials but considerable planning and commitment will be required for the
      expected benefits to be experienced nationally. Implementation of a successful
      national programme will involve attention to key areas such as programme
      management, recruitment and quality standards to deliver a high quality service
      to a substantial proportion of the eligible population.

PMID- 9612475
TI  - Hepatitis B virus carrier prevalence in New Zealand: population estimates using
      the 1987 police and customs personnel survey.
AB  - AIM: To estimate the population hepatitis B surface antigen (HBsAg) carrier
      prevalence for adults in New Zealand. METHOD: Data for 1987 from the New Zealand
      Police Department and New Zealand Customs Department hepatitis B sero-marker
      survey were further analysed. The sample size was 5510 staff who had completed a
      questionnaire, had blood sera taken and were not already immunised against
      hepatitis B. RESULTS: Maori adults had a HBsAg carrier prevalence of 5.43% (95%
      confidence interval 3.07-8.81), Pacific adults 4.44% (1.65-9.42), and European
      adults 0.42% (0.26-0.65). Other ethnic minorities and people with two or more
      self-assigned ethnic identities had a carrier prevalence of 3.85% (1.06-9.56).
      There were non-significant differences in this study for carrier prevalence by
      sex, age and region. CONCLUSIONS: Policy formation on screening programmes for
      hepatitis B carriers should assume a HBsAg carrier prevalence of about 5% for
      Maori, Pacific people and ethnic minorities, and about 0.5% for New Zealanders of
      European extraction.

PMID- 9612476
TI  - A clinical sample of Maori being treated for alcohol and drug problems in New
      Zealand.
AB  - AIMS: To document key clinical characteristics of a group of Maori being treated
      for alcohol and drug problems; compare the characteristics of Maori accessing
      dedicated Maori alcohol and drug treatment services with Maori accessing non
      dedicated services; and investigate these clinical characteristics in relation to
      patient satisfaction. METHODS: A sample of 105 Maori with alcohol and drug
      problems, accessing the range of treatment services in the Canterbury area,
      undertook a semi-structured interview. RESULTS: Overall this sample of Maori were
      socially disadvantaged. Their main drug of use was alcohol, followed by cannabis,
      opioids and sedatives/hypnotics. There were no significant differences between
      the subjects who attended Maori dedicated services and those who attended non
      dedicated Maori services in terms of demographic variables, alcohol and drug use
      history, current level of dependence, or anxiety/depression state. Subjects in
      dedicated Maori services were more likely to have had greater than 21 days of
      treatment compared to those in non-dedicated Maori services and were more likely
      to have been to their home marae than those in non-dedicated services. In
      multivariate analysis, Maori in dedicated Maori services were significantly more
      likely to be satisfied with treatment than those in non-dedicated services (odds
      ratio = 5.5, 95% confidence interval = 1.81-16.78). CONCLUSION: Further research
      is required to investigate the relationship between high patient satisfaction by
      Maori with alcohol and drug problems attending dedicated Maori treatment
      services, treatment effectiveness and the components of dedicated Maori services
      that may contribute to higher retention rates, greater patient satisfaction and
      increased positive treatment outcome.

PMID- 9612477
TI  - Factors associated with smoking and the reasons for stopping in Maori and
      Europeans: a comparative study.
AB  - AIM: To compare the prevalence of smoking, factors associated with smoking, ex
      smokers and reasons for stopping in Maori and Europeans aged 10 years and older.
      METHODS: Demographic and smoking data were obtained by personal interview using a
      standard questionnaire and assisted by Maori health carers. Report-back meetings
      were held. RESULTS: The smoking status in 713 subjects (Maori 52.5%, Europeans
      47.5%) was: current smokers (Maori 48.1%, Europeans 19.8%); never smoked (Maori
      28.1%, Europeans 47.5%); ex-smokers (Maori 23.8%, Europeans 32.7%). Of Maori
      smokers, 66.1% were women whereas of European smokers 47.8% were women.
      Significantly more Maori aged 10 to 29 years smoked than Europeans (p = 0.0002).
      Nineteen percent of smokers smoked < 5 cigarette equivalents per day, 68.8%
      smoked 5 to 20, and 12.2% smoked > 20 cigarettes per day. There was no gender
      difference in cigarette consumption. Maoridom (p = 0.00001), a less skilled
      occupation (p = 0.0008), lower income (< or = $15,000 p = 0.002) and alcohol
      consumption (p = 0.00001) were significantly associated with current smoking.
      Reasons for giving up smoking were health (majority), awareness of risks
      (Europeans), financial (Maori men), pregnancy (Maori women), social
      unacceptability (European women), on advice of medical practitioner (minority).
      CONCLUSIONS: Smoking remains a major problem in New Zealand, particularly in
      Maori. Stricter anti-tobacco measures than already exist, greater input from
      medical practitioners and particularly ongoing participation by Maori health
      carers should lead to a further decline in smoking.

PMID- 9612478
TI  - Ethnicity and methicillin-resistant S. aureus in South Auckland.

PMID- 9612479
TI  - Incidence of hepatitis C among New Zealand blood donors.

PMID- 9612480
TI  - Home nocturnal ventilation for chronic respiratory failure--a proven treatment?

PMID- 9612481
TI  - Physical assault in New Zealand: the experience of 21 year old men and women in a
      community sample.
AB  - AIM: To obtain epidemiological information on physical assault in a high risk
      group of New Zealanders. METHOD: Rates of physical assault in the preceding
      twelve months were ascertained by interview in a cohort of 21 year old, Dunedin
      born men (n = 482) and women (n = 462). RESULTS: Forty-five percent of the men
      and one quarter of the women reported at least one physical assault, either
      completed, attempted or threatened. A small proportion of these received medical
      treatment. Most serious assaults were by a perpetrator who was thought to have
      been drinking alcohol. Most assaults on men were by strangers but partners
      carried out more assaults against women, especially those receiving medical
      treatment. One quarter of all assaults on women were by other women, compared to
      15% of the assaults on men. Differences between patterns of assaults on women and
      on men are discussed. CONCLUSION: It is important for doctors to be aware of the
      widespread occurrence of interpersonal violence in New Zealand and its
      underreporting.

PMID- 9612482
TI  - Profile and cost of head injury patients admitted to the Waikato Hospital
      Intensive Care Unit.
AB  - AIMS: To examine the profile and hospital costs of head injury patients admitted
      to the Waikato Hospital Intensive Care Unit (ICU). METHODS: Data were collected
      on head injury patients admitted to ICU over 41 months and costs of head injury
      patients in ICU, the High Dependency Unit (HDU) and other wards were calculated.
      RESULTS: There were 286 head injury patients admitted to ICU, of whom 62% had a
      Glasgow Coma Score < or = 8. Times in the ICU and hospital were 1760 and 7352
      days respectively. Costs per day were $2280 in ICU, $800 in HDU and $500 in other
      wards. The cost for ICU was $1,174,478 per year, and for the total hospital
      treatment, $2.05 million (83 head injury patients) per year. Admissions of head
      injury patients to all New Zealand ICUs were 777 over the year to June 1996.
      Thus, assuming similar costs to the Waikato Hospital, New Zealand hospitals spend
      each year approximately 10.9 million dollars on head injury patients in ICUs and
      19 million dollars on overall hospital stays (including ICU). In a selected group
      of 123 severe head injury patients, the six month Glasgow Outcome Scores showed
      that 36% were in the moderate to severe disability categories and likely to cause
      major ongoing ACC costs. The costs of the 80% of head injury patients admitted to
      hospital but not admitted to ICU, and their prehospital and postdischarge costs
      were not studied. CONCLUSIONS: The New Zealand epidemic of head injuries
      continues to consume large amounts of the health money and produce major social
      costs.

PMID- 9612483
TI  - Generic surgical priority criteria scoring system: the clinical reality.
AB  - AIMS: To assess the 'generic surgical priority criteria' (GSPC) introduced into
      Auckland Hospital by the Northern Division of the Transitional Health Authority
      in 1997 and compare it with a score based on clinical judgement obtained using a
      linear analogue scale (LAS). METHODS: From the time of introduction in June 1997
      all patients being placed on the general surgical waiting list have been scored
      using both the GSPC and the LAS. After two months the scores given to 209
      patients were reviewed and compared. Correlation and limits of agreement analysis
      were performed for grouped data, cancer and benign groups. RESULTS: The data
      showed wide variation and poor agreement between the surgeons' clinical judgement
      in assessing priority for surgery and the score patients obtained using the GSPC.
      CONCLUSION: The GSPC has poor diagnostic discrimination as it failed to identify
      reliably a cancer diagnosis as high priority, with benign diagnoses scoring
      consistently higher. This highlights the need for clinical involvement in
      designing priority criteria and for formal validation of such tools.

PMID- 9612484
TI  - Lower cranial nerve palsies due to carotid artery dissection.

PMID- 9612485
TI  - Acute mountain sickness in the Southern Alps of New Zealand.
AB  - AIM: To assess the incidence and impact of acute mountain sickness in the
      Southern Alps of New Zealand. METHODS: Over a 22 month period, mountaineers in
      the Mount Cook region were asked to complete a questionnaire at the completion of
      their climbing excursions. The questionnaire recorded demographic data and
      incorporated the Lake Louise scoring system to assess the presence of acute
      mountain sickness. RESULTS: Of the 114 subjects who completed the questionnaire,
      30 (26%) developed acute mountain sickness. The incidence was higher amongst
      those who slept above 2500 m (50%). Of those with acute mountain sickness, 33%
      reported that their symptoms resulted in no reduction in activity, while 13%
      reported a moderate or severe reduction in activity. CONCLUSION: Mountaineers
      climbing in New Zealand's Southern Alps should be aware of the risk of acute
      mountain sickness, especially for those sleeping above 2500 m.

PMID- 9612486
TI  - Evidence based strategies for secondary prevention of ischaemic heart disease:
      time to improve clinical practice.

PMID- 9612487
TI  - Recreational use of oxygen.

PMID- 9612488
TI  - Asking pregnant women about HIV risk.

PMID- 9612489
TI  - Gemeprost pessaries for postpartum haemorrhage.

PMID- 9612490
TI  - Health and the human spirit for occupation.
AB  - The relationship between engagement in occupation and healthfulness is explored.
      Health is viewed not as the absence of organ pathology, but as possession of a
      repertoire of skills that enables people to achieve their vital goals in their
      own environments. This sort of health, reflecting adaptability and a good quality
      of life, is possible for all people, including those with chronic impairments.
      Theoretical and research literature from an array of disciplines explores the
      influences of occupation on various aspects of health. These include interests,
      satisfaction in everyday doing, balance, the latent consequences of work, and
      transcendence. Support is provided for a relationship between activity level and
      survival. To improve the life opportunities of those they serve, occupational
      therapists need to become ardent students of life's daily activities, grappling
      with the ambiguity and complexity of occupation, the occupational human, and the
      contexts in which occupation takes place.

PMID- 9612491
TI  - Clinical interpretation of "health and the human spirit for occupation".

PMID- 9612492
TI  - Occupation and well-being in dementia: the experience of day-care staff.
AB  - OBJECTIVE: The purpose of this study was to gain understanding of the staff
      experience of occupation in the context of day care for persons with dementia.
      METHOD: Narratives of especially satisfying and dissatisfying experiences of care
      were elicited from a random state-wide sample of day-care staff members.
      Qualitative methods were used to analyze the phenomenological data. RESULTS: The
      core meaning of occupation derived from these data was Occupation as the Gateway
      to Relative Well-Being. A model of the experience of occupation for staff members
      is proposed that is composed of three phases: the meeting of minds, engagement in
      occupation, and relative well-being. The skills of the staff informants that
      bring about the meeting of minds, the many levels of client engagement in
      occupation, and the indicators of well-being for clients and for staff members
      are described. The three phases together constitute an occupational space-
      created by the staff person--and the engagement in occupation itself constitutes
      an occupational place within that space. CONCLUSIONS: Bringing about indicators
      of well-being through occupation was a primary source of satisfaction for the day
      care staff informants in this study. The model of the staff experience of
      occupation proposed in this study has application to all areas of occupational
      therapy practice.

PMID- 9612493
TI  - Clinical interpretation of "occupation and well-being in dementia: the experience
      of day-care staff".

PMID- 9612494
TI  - Personal projects: a useful approach to the study of occupation.
AB  - A comprehensive and useful understanding of human occupation requires research
      methods that capture its individual dimensions while permitting analyses within
      and across groups. In this article we describe the construct of personal projects
      and the research method of personal projects analysis. Both have their origins in
      studies of personality and have been used successfully to link individual traits
      and context-based, goal-directed behavior to well-being and other variables. The
      appropriateness and relevance of this approach for studies of occupation and
      occupational therapy are considered.

PMID- 9612495
TI  - Effects of object affordances on reaching performance in persons with and without
      cerebrovascular accident.
AB  - OBJECTIVE: This study investigated whether affording objects with different
      levels of functional support would have an impact on reaching performance in
      patients after cerebrovascular accident (CVA) and in adults who were
      neurologically intact. Reaching performance was quantitatively analyzed, using
      several kinematic variables. METHOD: Two groups, 14 participants after CVA and 24
      age-matched adults who were neurologically intact, performed a food chopping task
      under two conditions: enriched affordances and impoverished affordances. Enriched
      affordances involved reaching forward to a chopper and pushing down on the handle
      to chop a fresh mushroom. Impoverished affordances involved reaching forward to a
      simulated chopper (i.e., a chopper covered with cardboard) without anything in it
      and then pushing the handle down. Reaching movement was measured by a three
      dimensional motion analysis system. RESULTS: For the CVA group, the enriched
      condition of reaching to chop the mushroom resulted in more efficient, direct,
      smooth, and preplanned movement than the impoverished condition of reaching to
      push on the chopper handle. The neurologically intact group responded similarly
      except that the participants' movement was equally smooth, as measured by
      movement unit, between the two testing conditions. Force generation, as
      characterized by peak velocity, was similar for both conditions for both groups.
      CONCLUSION: The finding that enriched affordances had a positive effect on
      movement kinematics in both CVA and neurologically intact groups suggests that
      providing natural objects for completing a task and providing functional
      information on the objects may enhance the functional performance of persons who
      have had a CVA. These findings should be replicated and extended to confirm the
      validity of these effects and allow for generalization.

PMID- 9612496
TI  - Creating opportunities for occupation: an intervention to promote the self-care
      independence of young children with special needs.
AB  - OBJECTIVE: The relationship between opportunities for occupation and the skill
      performance of young children with special needs was explored, using a multiple
      baseline across subjects design. METHOD: Three caregivers self-monitored the
      frequency with which they were able to create opportunities for their child to
      practice emerging self-dressing or self-feeding skills. RESULTS: Two caregivers
      quickly promoted self-care independence in their child by restructuring daily
      routines to provide more opportunities for the child to independently engage in
      the targeted occupation. One caregiver was unable to use the intervention
      techniques effectively. CONCLUSION: Opportunity for occupation can influence the
      child's skill performance and can be used as a treatment modality by some
      families.

PMID- 9612497
TI  - The value of occupation as the core of treatment: Sandy's experience.
AB  - Since 1917, when the occupational therapy profession was first established, the
      therapeutic value of occupation has been questioned, researched, valorized, and
      even trivialized. This article discusses one typical occupation-centered
      treatment, namely a community outing, the shopping spree. The purpose is to
      articulate the value of occupation-centered intervention and particularly (a) its
      importance for building rapport between patient and therapist so that genuinely
      meaningful treatment can be carried out; (b) its role in providing opportunities
      for patients to imagine futures through felt meanings and future images; and (c)
      its integrative qualities with respect to identities and performance components.

PMID- 9612498
TI  - Contrasting perspectives on work: an exploratory qualitative study based on the
      concept of adaptation.

PMID- 9612499
TI  - What is the proper domain of occupational therapy research?

PMID- 9612500
TI  - What is the source of occupation's treatment power?

PMID- 9612501
TI  - [Primary skin lymphomas: phenotypic characteristics of major clinical variants,
      classification].
AB  - Clinicomorphological characteristics of the most frequent forms of primary
      malignant skin lymphoma are given and their place in classifications of systemic
      diseases of hematopoietic and lymphoid tissue is shown. The use of specialized
      dermatological classification in practice of dermatologists is recommended.

PMID- 9612502
TI  - [Various aspects of immunohistochemical and molecular-biological characteristics
      of papillary cancer of the thyroid in children].
AB  - The dependence of the tumor cells differentiation upon the tumor
      histoarchitectonics, tumor type and patients' sex is studied
      immunohistochemically and by the in situ hybridization in 57 cases of thyroid
      carcinoma in children from the Belarus republic. A significant decrease of
      thyroglobulin synthesis and accumulation in the solid structures of papillary
      carcinoma is found. A decrease of the degree of the tumor biological
      differentiation in males is observed regardless of tumor histoarchitectonics.
      Increased accumulation of thyroglobulin (without change in its synthesis) in
      normal follicular epithelium found in parallel with increased intrathyroidal
      carcinoma dissemination and the size of the dominant tumor needs further
      investigation.

PMID- 9612503
TI  - [Immunohistochemical and ultrastructural characteristics of papillary carcinoma
      of the thyroid in people living in regions contaminated with radionuclides].
AB  - Papillary thyroid carcinoma was studied in 12 patients who lived in the
      radionuclide polluted and nonpolluted areas. Neither immunohistochemical nor EM
      differences in the structure of the carcinoma between the contaminated and non
      contaminated regions were found. Three structural variants were identified:
      classical, follicular and mixed, immunohistochemically having follicular-cell
      differentiation. Three EM types of cell were observed: dark, clear and
      intermediate.

PMID- 9612504
TI  - [Morphological characteristics of hyperplastic and adenomatous stomach polyps].
AB  - A morphological study of biopsy samples of gastric polyps from 224 patients was
      carried out. Four stages in gastric polyp morphogenesis were distinguished:
      foveolar hyperplasia, hyperplastic polyp, "two-floor" adenoma and adenoma. The
      correlation was established between the degree of Helicobacter pylori infection
      in the polyp mucous membrane on the one hand, and epithelial and stromal
      reactions (immuno-inflammatory reaction of stroma, chronic inflammation,
      formation of Russel bodies, cystes and chronic erosions) on the other. Greater
      content of stromal collagens, type IV collagen in case of gastric hyperplastic
      lesions was observed. Appearance and progression of gastric adenomatous growth in
      hyperplastic polyp correlates with an increase of type III collagen content,
      decrease of types I, IV, V collagens and fibronectin.

PMID- 9612505
TI  - [Functional morphology of adenohypophysis, thymus, and adrenal cortex in sudden
      infant death syndrome].
AB  - Adrenal glands, hypophysis and thymus of infants (mean age-4 months), who died of
      SIDS (30 cases), AVRI (10 cases) and violence (4 cases) were studied by
      morphometrical methods. The following changes in SIDS (in comparison with AVRI
      and violent death) were observed: a decrease of hypothesis weight with decreased
      quantity and size of basophil cells; reduced adrenal weight with thinning of the
      cortex particularly in the fascicular zone; diminished volumes of the nuclei in
      the adrenocortical cells of the fascicular zone; thymomegaly with hyperplasia of
      the thymus cortex; increased number of correlation links between morphometric
      indices of hypophysis and adrenal cortex. These changes may be indicative of a
      subclinical hypophyseal-adrenal insufficiency in SIDS. Adrenal cortex
      hypofunction was indirectly confirmed by the presence of thymomegaly. Long
      lasting glucocorticoid deficiency in secondary hypocorticoidism may cause sudden
      infant death following minor environmental causes.

PMID- 9612506
TI  - [Central nervous system lesions in fetuses and newborns in intrauterine infection
      caused by respiratory viruses].
AB  - Congenital respiratory viral infection is followed in the CNS of fetuses and
      newborns by grave dyscirculatory disturbances with glia proliferation and nervous
      tissue edema. The process is mainly localized in the periventricular regions of
      the brain ventricles. Neurologic and morphologic consequences of these damages in
      the CNS of fetuses and newborns need further studies.

PMID- 9612507
TI  - [Clinical morphology of pneumoconiosis].
AB  - Biopsies of human lungs were investigated at the light and electron microscopic
      level. The principle of pathological disturbances unity at various types of
      pneumoconiosis is formulated. Two morphological forms, two periods of development
      and four histological stages of pneumoconiosis morphogenesis are distinguished.

PMID- 9612508
TI  - [Abnormal branching of the left coronary artery from the pulmonary artery].
AB  - 13 hearts with the above congenital disturbance are studied. The disturbance of
      the space orientation of the anterior and posterior interventricular septa is
      found. The aortal and pulmonary valves are found to be oriented at an angle to
      each other, and the route of the left coronary artery is changed. These features
      allow to suggest that the anomalous issue of the left coronary artery from the
      pulmonary artery originates from the alterations of the interaction between the
      arterial valves and peritruncal ring. The choice of surgery depends on the heart
      anatomy in each individual case.

PMID- 9612509
TI  - [Clinico-morphological manifestations of genital tuberculosis in women].
AB  - Surgical material from 35 female patients with genital tuberculosis is analyzed.
      57.1% of patients with clear-cut clinical symptoms showed tubercles and caseous
      foci. In other patients no specific pathology was found histologically. This
      condition can be called as a non-active tuberculosis if clinicoepidemyologic data
      and laboratory studies support diagnosis of tuberculosis. Natural evolution of
      the specific inflammation and its trend to fibrosis facilitate the development of
      secondary infection. In this respect tuberculosis of female genitalia resembles
      pulmonary tuberculosis.

PMID- 9612510
TI  - [Morphology of epileptic leukoencephalopathy].
AB  - Special interest has never been focused on the pathology of white matter in the
      epileptogenic brain. In the authors' material obtained from 129 patients in the
      course of the open surgery because of temporal epilepsy marked alterations of the
      white matter of the temporal lobe were found. These alterations include different
      processes which can be combined in general syndrome of epileptic
      leukoencephalopathy. Changes in the vascular system of the brain include:
      arterial wall sclerosis, hyalinosis, and arterial convolution development,
      abnormal structure of the brain blood barrier. Pathology of myelin include heavy
      damage of sheets and total demyelinisation of some axons. Cyst formation with
      complex walls; gliosis-apparently the majority part of cells are young
      astrocytes. All these alterations in white matter contribute to pathogenesis of
      epilepsy.

PMID- 9612511
TI  - [Variants and stages of regional lymph nodes sclerosis in lymphedema].
AB  - The inguinal lymph nodes of patients with primary lymphedema of lower extremities
      were investigated by light microscopy. It was found that sclerotization of
      regional lymph nodes can begin with both cortical and medullary parenchyma.
      Different stages of this process in lymph nodes were distinguished. These stages
      depend on the duration of the illness and the zone of organ where the first signs
      of sclerotization were observed. Small islands of lymphoid parenchyma were found
      in even well advanced sclerosis lymph nodes, and this allows to assume
      possibility of full regeneration of all structure of these organs when lymph
      circulation is normalized.

PMID- 9612512
TI  - [Morphofunctional characteristics of the testis of albino rats exposed to dioxin
      containing herbicide 2,4-D].
AB  - Endocrine system of the gonads of white rats after subacute poisoning with 2,4-D
      was studied. Signs of increased steroidogenesis in Leydig cells, a decrease of
      plasma testosterone concentration and decrease of the gonad sensitivity to
      chorionic gonadotropin were observed.

PMID- 9612513
TI  - [Cystic fibrosis in adolescent patients].
AB  - Summary--An autopsy observation of mucoviscydosis in a female who died at the age
      of 17 with a prevalent affection of the bronchopulmonary system is reported.
      Pronounced cystic fibrosis with atrophy and lipomatosis of the pancreas was
      found. The cause of death was respiratory failure in spite of intensive
      antibacterial therapy. Bullous emphysema with frequent pneumothorax in adults
      with this disease considerably worsens the prognosis and requires urgent therapy
      which in this case was not conducted because of late hospitalization.

PMID- 9612514
TI  - [Elastofibroma].

PMID- 9612515
TI  - [Metastasis of squamous cell carcinoma of the penis into the heart].
AB  - A casuistically rare autopsy case of penile squamous cell carcinoma metastasis
      into the interventricular septum in a 70-year-old patient is described. The
      patient was operated because of suspected paraphymosis and diagnosis of carcinoma
      was established after histological examination of the surgical material. This
      diagnosis was followed by the penis amputation. The cause of death was the heart
      block due to a massive (3.5 cm in diameter) heart metastasis which was not
      suspected clinically.

PMID- 9612516
TI  - [Local computer network in the pathological anatomy bureau].

PMID- 9612517
TI  - [Various aspects of pathogenesis and pathology of bronchial asthma].
AB  - Participation in bronchial asthma pathogenesis of the epithelium, bronchial wall,
      effector cells of inflammation at various periods of the disease are described.
      Morphology of the bronchi between the attacks, at the height of the attack and at
      the experimental model of the bronchospasm is presented. The hypotheses of the
      bronchospasm and respiratory tract obstruction are discussed.

PMID- 9612518
TI  - [Morphological and morphogenetic characteristics of erysipelas inflammation].
AB  - Literature information on morphology and morphogenesis of erysipelas inflammation
      is analysed in the light of macroscopic, microscopic and histochemical data.
      Alterations of the epidermis and derma (epidermocytes, fibroblasts, macrophages,
      plasmocytes and labrocytes) in the foci of inflammation are described in detail.
      Deficiency of the local mechanisms plays a leading role in chronization of the
      disease. A pathogenetic role of circulating and tissue associated immune
      complexes is shown. It is claimed that further study of skin parenchymatous and
      stromal component and their interaction in both focus of inflammation and outside
      of it may help in revealing specific parts of erysipelas inflammation
      pathogenesis.

PMID- 9612519
TI  - [Comment on the article by N.L. Chazova et al "Controversial aspects of
      verification and classification of thyroid tumors (Arkh Patol, 1997, No.1, pp 33
      36)].

PMID- 9612520
TI  - Surgical standby for coronary interventions.

PMID- 9612521
TI  - Rediscovering ionised calcium.

PMID- 9612522
TI  - Haemochromatosis: diagnosis and management after the cloning of the HFE gene.

PMID- 9612523
TI  - Percutaneous transluminal coronary angioplasty (PTCA) without on-site surgical
      facilities.
AB  - BACKGROUND: Numerous publications from European and Canadian centres have
      documented the feasibility of performing percutaneous transluminal coronary
      angioplasty (PTCA) without on-site surgical facilities. The absolute need for
      surgical standby has been changing especially with the introduction of coronary
      stent for bailout situations. This practice may be applicable in Australian
      centres especially in the environment of long waiting lists and cost containment.
      AIM: To review the safety of performing PTCA by experienced operators in two
      Melbourne hospitals without on-site surgical facilities. METHODS: We reviewed
      data of all patients who had PTCA electively (with low and moderate risks)
      between July 1996 and January 1997 and in the setting of acute myocardial
      infarction (AMI) from January 1996 to January 1997. Surgical standby was
      available as 'next available room' basis in nearby centres. Immediate outcome
      before discharge was documented and follow up from three to six months in 80% of
      all surviving patients. RESULTS: There were 46 elective PTCA and 41 PTCA for AMI.
      PTCA was successful in 82 (94%) patients. Among the elective cases, seven
      patients were already inpatients with unstable or postinfarct angina. Thirteen
      patients had stents deployed with three for acute closure. Abciximab (Reopro) was
      given to eight patients. Two patients had acute closure in the laboratory which
      could not be reopened, but did not require emergency coronary artery bypass
      grafting (CABG). There were four inhospital deaths (three related to AMI and one
      died of a noncoronary cause). CONCLUSION: PTCA can be performed electively in a
      selected group of patients with coronary artery disease and as a primary
      procedure for AMI without on-site surgical standby.

PMID- 9612524
TI  - High prevalence of normal total calcium and intact PTH in 60 patients with proven
      primary hyperparathyroidism: a challenge to current diagnostic criteria.
AB  - BACKGROUND: Others have reported a clear distinction between patients with
      primary hyperparathyroidism (PHPT) and normal subjects using the intact PTH
      (iPTH) assay. AIM: We reviewed our last 60 surgically proven cases of PHPT, who
      had adequate preoperative biochemical assessment, to determine the usefulness of
      the iPTH assay, ionised calcium and other biochemical criteria in differentiating
      between normal subjects and patients with PHPT. METHODS: We conducted a
      retrospective cross-sectional study of all patients with surgically proven PHPT
      who had been referred to Sir Charles Gairdner Hospital, Perth, Western Australia
      for preoperative biochemical assessment. All cases had fasting preoperative blood
      and urine samples collected for ionised calcium, plasma total calcium, albumin,
      urine calcium excretion, renal phosphate threshold and iPTH. RESULTS: Fifty cases
      had a single or double adenoma and ten had hyperplasia. All except one had
      ionised hypercalcaemia but only 47 (78%) had an elevated corrected total calcium
      (cCa). Therefore 13 cases (22%) had a normal cCa and five of those patients (8%)
      had both an iPTH and cCa within the reference range. Forty-nine (82%) had an
      elevated ionised calcium (iCa) and iPTH; the remaining 11 (18%) had an iPTH
      within the reference range. Of this latter 18%, ten (91%) had a low renal
      phosphate threshold and five (45%) had significant renal calcium conservation:
      all 11 cases had at least one abnormality in the renal handling of calcium or
      phosphate and all normalised their plasma calcium postoperatively (ionised and
      corrected total calcium). CONCLUSIONS: One in five patients with proven PHPT have
      a non-elevated cCa and/or intact PTH. Ionised calcium should be measured in all
      suspected cases. Additional studies of renal calcium and phosphate handling are
      helpful to establish a diagnosis where any uncertainty exists.

PMID- 9612525
TI  - Oral cyclosporin in refractory inflammatory bowel disease.
AB  - BACKGROUND: The role of cyclosporin in patients with severe, refractory
      inflammatory bowel disease is unclear. METHODS: A seven year retrospective review
      of patients treated with oral cyclosporin for inflammatory bowel disease
      refractory to conventional medical therapy was undertaken. RESULTS: Twenty-eight
      patients (13 ulcerative colitis and 15 Crohn's disease) received oral cyclosporin
      for a mean of nine months (range 0.25-27 months). Within four weeks of starting
      cyclosporin, a complete clinical response occurred in 15 patients (nine with
      ulcerative colitis and six with Crohn's colitis), in whom conventional
      maintenance treatment was instituted concurrently. The clinical response was
      sustained during cyclosporin treatment in ten, but maintained after cyclosporin
      withdrawal in only five patients (18% of entire study group). Four of the five
      patients who relapsed after cyclosporin withdrawal had failed previously to
      respond to azathioprine. None of the five patients with continuing remission
      after cyclosporin withdrawal had received azathioprine in the past. There were
      three clinically significant infections and 14 cases of impaired renal function
      during treatment. CONCLUSIONS: Oral cyclosporin induces remission in some
      patients with severe ulcerative colitis or Crohn's colitis, but its benefits in
      cases refractory to azathioprine are over-shadowed by a high frequency of relapse
      after drug withdrawal.

PMID- 9612526
TI  - KRAS codon 12 mutations in Australian non-small cell lung cancer.
AB  - BACKGROUND: In certain non-small cell lung cancer (NSCLC) populations, codon 12
      mutations of the KRAS oncogene comprising mostly G-T transversions have
      diagnostic and prognostic value. However, it is not known if these findings are
      applicable to all populations of lung cancer patients. AIMS: To examine for KRAS
      codon 12 mutations in Australian NSCLC patients. METHODS: Tumour samples and
      corresponding normal lung tissue from 108 Australian patients with NSCLC
      undergoing curative resection were studied for mutations of KRAS codon 12 using a
      sensitive PCR assay. Mutations were confirmed by DNA sequencing and correlated
      with histological subtype, tumour stage, the presence of nodal metastases and
      survival. RESULTS: Eleven KRAS codon 12 mutations were detected in 108 NSCLCs,
      with most (8/11) occurring in the adenocarcinoma subtype (17% prevalence), but
      were not associated with adverse outcome or clinico-pathological features. G-T
      transversions were surprisingly infrequent (37% of adenocarcinoma mutations).
      CONCLUSIONS: These data add to the evidence suggesting geographical differences
      in the spectrum and significance of KRAS codon 12 mutational genotypes in NSCLC.
      While these may be due to genetic variation and/or differences in carcinogen
      exposure, there is a need for larger population based studies before this
      potentially important biomarker can be recommended universally for optimising
      lung cancer management.

PMID- 9612527
TI  - Progress in management of acute myeloid leukaemia (AML) in Australia since 1980:
      a single institution retrospective study.
AB  - BACKGROUND: Much research has been conducted into the pathobiology, diagnosis,
      and management of acute myeloid leukaemia (AML) since 1980, with major
      contributions from Australian studies in this period. AIMS: To determine whether
      advances in basic and clinical research into AML have translated into improved
      survival for patients in the community. METHODS: A retrospective survey of
      records of all patients with AML presenting to the Royal Melbourne Hospital (RMH)
      over a 16 year period, analysed according to induction therapy and established
      prognostic factors. Between 1980 and December 1996 223 (98%) of 227 patients were
      evaluable. RESULTS: The probability of survival at five years for patients
      treated since 1990 has improved significantly compared to the cohort treated
      between 1980-89 (34 +/- 5% vs 4 +/- 2%; mean +/- standard error). This benefit is
      most evident in patients less than 60 years of age (50 +/- 7% vs 11 +/- 4%).
      Successive induction protocols in the context of clinical trials conducted since
      1985 contributed to improved outcomes. The selective application of bone marrow
      transplantation, and use of retinoic acid as induction therapy for acute
      promyelocytic leukaemia has also improved survival. Despite increases in dose
      intensity, early death rates for patients undergoing induction therapy fell
      during the study period. CONCLUSIONS: Participation in clinical and basic
      research with the development of more intense and specific treatments for
      patients with AML has contributed to better outcomes, underpinned by improvements
      in supportive care.

PMID- 9612528
TI  - Video push enteroscopy in the investigation of small bowel disease: defining
      clinical indications and outcomes.
AB  - BACKGROUND: Push enteroscopy is a new technique for investigation of the small
      intestine. The clinical indications are still being defined. It also offers the
      potential for therapeutic intervention in suitable cases. AIMS: To evaluate
      further the role of push enteroscopy in the diagnosis and treatment of patients
      with suspected or known small bowel disease. METHODS: A prospective record was
      kept of all patients having enteroscopy at Royal Prince Alfred Hospital between
      March 1995 and July 1997. The procedure was performed 73 times in 68 patients.
      Indications and diagnoses were noted. The outcome in patients with obscure
      gastrointestinal bleeding or anaemia in whom a vascular lesion was treated with a
      heater probe was also determined. RESULTS: Enteroscopy was performed in 23
      patients for gastrointestinal bleeding of obscure origin. An active or possible
      bleeding source was found in 13 (57%). The commonest of these was jejunal
      angiodysplasia. In the 21 patients with chronic iron deficiency anaemia a lesion
      was found in ten (48%). The majority of these were in the stomach, as described
      by others. The diagnostic yield in the 16 patients having enteroscopy for known
      or suspected small bowel disease was 56%. One patient underwent balloon
      dilatation of a postoperative jejunal stricture. Eleven patients with obscure
      bleeding or anaemia had ablation of a vascular lesion with a heater probe.
      Transfusion requirements fell after this procedure, particularly in those with
      active bleeding at the time of the examination. In five of the 11 no further
      transfusions were required in over six months of follow-up. CONCLUSIONS: The most
      common indications for enteroscopy are obscure gastrointestinal bleeding, chronic
      anaemia and known or suspected small bowel disease. A positive result can be
      expected in over 50% of patients. The treatment of vascular lesions via the
      enteroscope has a significant impact of subsequent transfusion requirements.

PMID- 9612529
TI  - Difficulties in the diagnosis of apical hypertrophic cardiomyopathy (AHCM).

PMID- 9612530
TI  - Diabetes and hyperglycaemia among patients with myocardial infarction in a
      multiethnic population.

PMID- 9612531
TI  - Ruptured internal mammary artery aneurysm presenting as massive spontaneous
      haemothorax in a patient with Ehlers-Danlos syndrome.

PMID- 9612532
TI  - Another case of high gentamicin clearance and volume of distribution in a patient
      with high output ileostomy.

PMID- 9612533
TI  - Relapsing thrombotic thrombocytopenic purpura (TTP) in Sjogren's syndrome.

PMID- 9612534
TI  - Cytopenias secondary to copper depletion complicating ammonium tetrathiomolybdate
      therapy for Wilson's disease.

PMID- 9612535
TI  - Dilated cardiomyopathy associated with anti-neutrophil cytoplasmic antibodies.

PMID- 9612536
TI  - Venlafaxine withdrawal syndrome.

PMID- 9612537
TI  - Relapsing neurological melioidosis from the top end of the Northern Territory.

PMID- 9612538
TI  - Precision of bone density measurement.

PMID- 9612539
TI  - Early management and outcome of acute stroke in Auckland.

PMID- 9612540
TI  - Relapse of central nervous system Burkitt's lymphoma presenting as Guillain-Barre
      syndrome and syndrome of inappropriate ADH secretion.

PMID- 9612541
TI  - Snoring and halitosis in a dog.

PMID- 9612542
TI  - Giardia infection in budgerigars.
AB  - Budgerigars (Melopsittacus undulatus) from two different breeding colonies were
      found to have Giardia infection. Light microscopy, scanning electron microscopy
      and in-vitro and in-vivo studies confirmed the species was G psittaci. Chicks
      were clinically affected and showed signs of retarded growth, dehydration and
      diarrhoea. The faeces of adult birds treated with metronidazole in drinking water
      were negative for Giardia 5 days after treatment. Megabacteria were also found in
      adult birds but were not treated. This study extends the known host range for
      Giardia in Australia to include budgerigars.

PMID- 9612543
TI  - Atrioventricular valve dysplasia in dalmatians.

PMID- 9612544
TI  - Congenital meningocele with a rare skull defect in a lamb.

PMID- 9612545
TI  - Streptococcal peritonitis in a young dromedary camel.
AB  - A male dromedary camel was presented for a primary Streptococcal zooepidemicus
      septic peritonitis. An underlying gross lesion was not identified during
      abdominal exploratory surgery. The camel responded to peritoneal lavage,
      peritoneal drainage and systemic antibiotic therapy. Thrombophlebitis of the left
      jugular vein was diagnosed 14 days after surgery. The camel died of an unknown
      cause 24 days after surgery.

PMID- 9612546
TI  - Plasma cortisol responses to three corticotrophic preparations in normal dogs.
AB  - OBJECTIVE: To compare cortisol responses to three corticotrophic preparations in
      normal dogs. ANIMALS: Eight clinically normal dogs (four intact males, four
      intact females) of medium size. PROCEDURES: Each dog received four treatments on
      four separate occasions in a duplicated Latin square pattern. Treatments were two
      adrenocorticotrophin (ACTH) preparations given intramuscularly at 2.2 U/kg, one
      of the ACTH preparations given intramuscularly at 1 U/kg and a synthetic
      polypeptide with ACTH-like activity (tetracosactrin, cosyntropin) given
      intravenously at 5 micrograms/kg. Plasma samples were taken for cortisol assay
      before and at 0.5, 1, 2 and 4 h after treatment. RESULTS: Plasma cortisol
      concentrations were similar with the two ACTH preparations and at both dose
      rates. Tetracosactrin produced smaller mean peak cortisol concentrations, which
      tended to occur earlier than with ACTH, and smaller values for the area under the
      curve of plasma cortisol concentration from zero time to 4 h. CONCLUSION: The
      findings suggest that canine adrenal function can be tested adequately by giving
      ACTH intramuscularly at 1 U/kg and measuring plasma cortisol in samples taken at
      0 and 2 h, or by giving tetracosactrin intravenously at 5 micrograms/kg and
      determining cortisol concentration at 0 and 1 h.

PMID- 9612547
TI  - Gentamicin in dairy cows.

PMID- 9612548
TI  - Antiparasitic drugs, the livestock industry and dung beetles--cause for concern?

PMID- 9612549
TI  - The 1872 outbreak of foot-and-mouth disease in Australia--why didn't it become
      established?

PMID- 9612550
TI  - Comparative effects of abamectin and two formulations of ivermectin on the
      survival of larvae of a dung-breeding fly.
AB  - OBJECTIVES: To compare the survival of larvae of a dung-breeding fly in the
      faeces of cattle treated either with an injectable formulation of abamectin, or
      with oral or injectable formulations of ivermectin. DESIGN: Replicated bioassays
      were conducted on larvae of the bush fly, Musca vetustissima, using faeces
      collected before and at intervals after drug treatment. ANIMALS: Two cows and
      their calves were allocated to each of three drug treatments and dosed according
      to individual weights. PROCEDURES: Differences in the proportions of larvae
      pupariating were used as measures of the toxicity of drug residues. RESULTS:
      Development of fly larvae was inhibited in all faeces collected 1 to 4 days after
      treatment. In cattle treated with oral ivermectin, there was reduced larval
      survival in faeces collected 8 and 16 days after treatment, but by day 32,
      survival was equivalent to that recorded in the faeces of untreated cattle. With
      injectable ivermectin, there was no survival at day 8, limited survival at day 16
      and, at day 32, survival was not significantly affected. With injectable
      abamectin, survival was completely suppressed until day 32, at which time the
      number of pupariating larvae did not differ significantly from that recorded in
      faeces from untreated animals. CONCLUSION: The oral formulation of ivermectin is
      eliminated more rapidly than the injectable formulation and, as a consequence, is
      likely to be less harmful to dung-feeding insects. Abamectin and ivermectin
      appear to equally toxic larvae of M vetustissima.

PMID- 9612551
TI  - Effects of residues of deltamethrin in cattle faeces on the development and
      survival of three species of dung-breeding insect.
AB  - OBJECTIVE: To assess the toxicity to insects of drug residues excreted in cattle
      faeces following treatment with deltamethrin. DESIGN: Bioassays were performed on
      one species of dung-breeding fly (Musca vetustissima) and two species of dung
      beetle (Onthophagus binodis and Euoniticellus fulvus). ANIMALS: Cattle on
      properties near Kangaroo Valley, Canberra and Gundagai were treated with pour-on
      formulations of deltamethrin. Untreated animals acted as controls. PROCEDURES:
      Faeces from treated and untreated cattle were inoculated with newly emerged fly
      larvae or fed to adults of two species of dung beetle. Percentage survival and
      duration of development provided measures of the toxicity of deltamethrin
      residues in faeces. RESULTS: Residues of deltamethrin were excreted in
      concentrations sufficient to inhibit survival of larvae of M vetustissima for 1
      to 2 weeks after treatment. Peak concentrations of 0.4 mg deltamethrin/kg dry
      weight of faeces occurred 3 days after treatment and were sufficient to kill
      adult beetles for at least twice this period. With one of two formulations
      tested, there was evidence of a reduction in dung beetle fecundity and an
      increase in the duration of juvenile development. A model of the effect of
      deltamethrin on the breeding success of dung beetles in the field suggests that a
      single treatment, applied when most of the population is in a nonparous
      condition, may cause up to 75% reduction in beetle activity by the end of the
      season. Multiple treatments at 10 or 21 day intervals may drive local populations
      towards extinction. CONCLUSION: Depending on the time and frequency of treatment,
      the effect of deltamethrin on insects in cattle faeces may range from negligible
      to catastrophic.

PMID- 9612553
TI  - Revised Australian Code of Practice for the care and use of animals for
      scientific purposes.

PMID- 9612552
TI  - Effects of local anaesthesia of 4 to 8 hours' duration on the acute cortisol
      response to scoop dehorning in calves.
AB  - OBJECTIVE: To determine the effect of a long-acting local anaesthetic on the
      plasma cortisol response in calves dehorned using a scoop. DESIGN: A
      physiological study with controls. PROCEDURE: Seventy female calves, 3 to 4
      months old, were divided into seven groups and dehorned by scoop with or without
      a long acting local anaesthetic (bupivacaine) which provides local anaesthesia
      for 3 to 4 h. In some treatment groups the local anaesthetic was given a second
      time, after 4 h, to give 8 h of anaesthesia. Blood samples were taken before and
      for 9 h after treatment and plasma cortisol concentrations were measured.
      RESULTS: Scoop dehorning caused a marked rise in plasma cortisol concentration,
      which returned to pre-dehorning values after 7 h. The cortisol concentrations of
      calves given bupivacaine were similar to those of control animals for 4 h after
      dehorning, but then a significant and protracted rise occurred, with
      concentrations returning to pretreatment values at about 9 h after dehorning. In
      calves given a second treatment of bupivacaine 4 h after dehorning, the plasma
      cortisol concentration remained similar to control values for 8 h after dehorning
      but then increased sharply. CONCLUSIONS: During its period of activity long
      acting local anaesthetic prevented the rise usually seen after scoop dehorning in
      plasma cortisol concentrations; by inference it also alleviated the pain-induced
      distress caused by this procedure. However, when its effects had worn off the
      plasma cortisol values rose sharply indicating that animals still experienced
      pain-induced distress despite local anaesthetic being administered.

PMID- 9612554
TI  - Reduction and recovery of N-acetylglucosamine-1-phosphate transferase activity in
      the liver of sheep and rats after a single subcutaneous dose of tunicamycin.

PMID- 9612555
TI  - Lack of effect of tunicamycin on spermatogenesis in rams.

PMID- 9612556
TI  - [Complete amino acid sequence of catalase from the fungus Penicillium vitale].
AB  - The polypeptide sequence of the unmodified catalase from Penicillium vitale
      containing 696 amino acid residues was deduced. The sequences of 76 tryptic
      peptides of the unmodified catalase, 63 tryptic peptides of the catalase with
      modified Lys residues, 48 peptides resulting from catalase cleavage by the
      Staphylococcus aureus V8 protease, and 9 fragments obtained by BrCN-treatment
      were considered, and a comparison with the sequences of other catalases was made.

PMID- 9612557
TI  - [Characteristics of N-terminal 60-kDa fragment of elongation factor 2].
AB  - The N-terminal 60-kDa-fragment of elongation factor 2 from rat liver (EF-2) was
      obtained by the limited proteolysis of native EF-2 with elastase. This fragment
      consists of 506 N-terminal amino acid residues of EF-2. The conformational
      properties of both this fragment and EF-2 in solution were studied by circular
      dichroism and fluorescent spectroscopy. The contents of secondary structure
      components in the fragment and in the factor that were deduced from CD
      measurements agreed well with values predicted from their primary structures.
      Both proteins were resistant to denaturation with < or = 3 M urea and exhibited
      cooperative denaturation transitions. Temperature melting also proceeded
      cooperatively for the fragment and EF-2. Structural properties of the N-terminal
      60-kDa-fragment are discussed in comparison with the biochemical characteristics
      and 3D structure of prokaryotic elongation factor EF-G.

PMID- 9612558
TI  - [Determination of activity of aspartic proteinases by cleavage of new chromogenic
      substrates].
AB  - Chromogenic hexapeptides Dnp-Ala-Ala/Ser-Phe-Phe-Ala-Arg-NH2 containing a Phe-Phe
      bond, which is sensitive to aspartic proteinases, were used as substrates for
      assaying the activity of pepsin, chymosin, and aspergillopepsin A. The assay was
      performed after the separation of hydrolyzates on SP-Sephadex by measuring at 360
      nm the absorbance of the dinitrophenylpeptide lacking the cationic group, which
      was formed upon the cleavage of the substrate. The kinetic parameters of the
      hydrolysis of the substrates were evaluated. It is shown that replacing the Ala
      residue with Ser in the P2 position does not substantially change the kinetic
      parameters. The substrates were hydrolyzed by pepsin several times faster than by
      aspergillopepsin A or chymosin. The method is sensitive and enables the activity
      of aspartic proteinases to be determined easily.

PMID- 9612559
TI  - [New donor-acceptor pairs for fluorogenic substrates with intramolecular
      fluorescence energy transfer for thrombin and trypsin].
AB  - New substrates for thrombin and trypsin are described: a fluorogenic substrate
      Abz-Pro-Arg-Gly-Nph (I), whose action is based on intramolecular fluorescence
      energy transfer, and H-D-Trp-Pro-Arg-pNA (II), which can be used both as a
      chromogenic substrate and as a substrate with the intramolecular fluorescence
      energy transfer. In substrate (I), a 4-nitrophenylhydrazide group was first used
      as an acceptor of excitation energy of the 2-aminobenzoyl group. The substrate is
      poorly hydrolyzed by thrombin (kcat/K(m) = 1.4 x 10(3) M-1 s-1) and is
      efficiently cleaved by trypsin (kcat/K(m) = 3.15 x 10(6) M-1 s-1). The hydrolysis
      of (II) can be monitored both spectrophotometrically, by absorbance at 405 nm,
      and from the increase in fluorescence at 340 nm. In the efficiency of hydrolysis
      with thrombin (kcat/K(m) = 3.0 x 10(6) M-1 s-1), compound (II) is comparable with
      the known chromogenic substrates for this enzyme. The proposed donor-acceptor
      pairs are promising in designing substrates with the intramolecular fluorescence
      energy transfer for a variety of proteolytic enzymes.

PMID- 9612560
TI  - [cDNA cloning of three new homeobox-containing genes of Anf class from human,
      chicken and newt].
AB  - On the basis of the analysis of cDNA of three new homeobox-containing genes from
      human, chicken, and newt, a new class of homeobox genes Anf is characterized
      homologous to the Xanf-1 gene from Xenopus laevis, earlier cloned by us. These
      genes may be largely involved in the specification of embryonic subdivisions in
      the forebrain region of the embryo. The homeodomains of the proteins encoded by
      these genes differ greatly in the primary structure from all previously described
      homeobox genes. The high variability of the homeodomain sequences of the proteins
      of this class imply their rapid evolution.

PMID- 9612561
TI  - [New DNA diagnostic system for determination and identification of homo- and
      heterozygote point mutations].
AB  - A straightforward and effective PCR-based assay system is devised that allows one
      to reveal and identify homozygous and heterozygous point mutations. The system
      uses two sets of allele-specific primers. In one set, the 3'-nucleotide matches
      the allele under study so that the primer functions effectively only if the DNA
      contains the corresponding allele. To increase primer specificity, template
      noncomplementary nucleotides are introduced near its 3'-end. The primers from
      another set invariably bear a 3'-terminal mismatch, and, in addition, the mutant
      nucleotides of the alleles under study form mismatches with the internal
      nucleotides of the primers. In such combination, the primer activity is
      suppressed if the DNA contains a homozygous mutation. The assay system devised
      was utilized to reveal the Leiden mutation in the gene for factor V of the human
      blood clotting system in patients with thrombophilia.

PMID- 9612562
TI  - [Interaction of derivatives of short oligonucleotides with nucleic acids. VIII.
      Characteristics of target DNA modification by alkylating oligonucleotide
      derivatives in tandem complexes].
AB  - The influence of effectors [octanucleotides and their 3',5'-di-N-(2
      hydroxyethyl)phenazinium derivatives] on the modification of a target DNA by
      alkylating oligonucleotide derivatives forming duplexes of different stability
      with the target ws studied. It is shown that, being in tandem complexes
      immediately adjacent to the reactive group of an oligonucleotide reagent
      possessing a high hybridization capacity, the effector, on the one hand, enhances
      the stability of the reagent target duplex, and on the other hand, changes the
      site-specificity of alkylation and decreases the efficiency of the target
      modification at temperatures that provide a high extent of the target association
      with the reagent. Conversely, in the case of oligonucleotide reagents forming
      weak complexes with the target, effectors enhance both the stability of the
      target.reagent duplex and the extent of the target throughout the temperature
      range tested. The data indicate that the varying influence of effectors on the
      target modification by reagents with different hybridization capacities is due to
      conformational features of the target reagent duplexed regions. Increasing the
      rigidity of the target.reagent duplex reduces the efficiency of the target
      modification in tandem complexes.

PMID- 9612563
TI  - [Determination and identification of beta-1,3;1,6-glycooligosaccharides in
      laminarioligosaccharide mixtures by means of enzymologic transglycosylation.
      Oligosaccharides with degree of polymerization of 5 and 6].
AB  - 1-->3; 1-->6-beta-D-Glucooligosaccharides with polymerization degree of 5-6 were
      obtained from laminaran and analyzed by the previously developed method [1] by
      using them as donors and p-nitrophenyl beta-D-glucoside as the acceptor in the
      transglycosylation reaction catalysed by endo-1-->3-beta-D-glucanase LIV. The
      resulting homologous p-nitrophenyl beta-1,3-laminarioligosides with
      polymerization degree of 2-6 and the corresponding derivatives of mixed beta-1,3;
      1,6-glucooligosaccharides with the same polymerization degree were analyzed by
      HPLC. The latter compounds exhibited higher retention times than the former with
      the same polymerization degree. Isomeric tetra-, penta-, and hexameric compounds
      were detected, and some of them were structurally characterized by means of NMR.
      The suggested method of analysis of oligosaccharide mixtures is simple,
      informative, and consumes a minimal quantity of sample.

PMID- 9612564
TI  - [Synthesis of p-nitrophenyl laminarioligosides via transglycosylation reaction
      catalyzed by endo-1,3-beta-D- glucanase from marine mollusk].
AB  - The transglycosylation reaction catalyzed by endo-1,3-beta-D-glucanase LIV from
      the marine mollusk Spisula sachalinensis was studied with the goal of preparing p
      nitrophenyl (Np) 1,3- and 1,3; 1,6-D-glucooligosides. As donors we used the
      1,3;1,6-beta-D-glucans with various content of beta-1, 6-glucoside bonds:
      laminarians [from Laminaria cichorioides (10%), L. gurjanovae (2%), and Fucus
      evanescens (35%)] and translam (25%); as acceptor we used the p-nitrophenyl beta
      D-glucoside (GNp). The maximal yield of the transglycosylation products was found
      when using laminaran from Laminaria cichorioides; donors with a lower or higher
      content of beta-1,6-glucoside bonds were less efficient. The laminaran from F.
      evanescens and translam gave no Np-laminaribioside. At optimal conditions (10
      mg/ml of laminaran from L. cichorioides and 5 mg/ml of GNp), maximal yields of Np
      laminaribioside, Np-trioside, Np-tetraoside, and Np-pentaoside were 19, 8, 3, and
      1%, respectively. The first two compounds were isolated by chromatography on
      silica gel, their physicochemical characteristics were obtained, and their
      structures were established by 13C NMR spectroscopy.

PMID- 9612565
TI  - [Incorporation of neoglycolipids into K562 cells. Model for the study of
      carbohydrate dependent lysis of target cells by natural killer cells].
AB  - A model system was developed to study the role of cell surface oligosaccharides
      in cytotoxicity mediated by natural killer (NK) cells. Polymeric glycoconjugates
      Glyc-PAA-PE and Glyc-PAA(Flu)-PE (where Glyc is the 3-aminopropyl Le(x) residue,
      PAA is the poly(N-2-hydroxyethylacrylamide) matrix, Flu is the residue of a
      fluorescein derivative, and PE is the phosphatidylethanolamine residue) were
      synthesized, and their association with the membranes of living K562 cells was
      studied.

PMID- 9612566
TI  - [Matrix metalloproteinases and their biological functions].
AB  - Matrix metalloproteases (MMPs) play a key role in the metabolism of connective
      tissue proteins in the norm and in pathology. Major MMP subfamilies
      (collagenases, gelatinases, and stromelysins) and matrixins, which have not been
      attributed to any subfamily, are reviewed. The main characteristics of these
      enzymes; their structural properties; their specificity; the regulation of their
      activity; and their role in the normal development of the matrix, the oncogenic
      transformation of the cell, and angiogenesis are discussed.

PMID- 9612567
TI  - [Glutamylendopeptidases from microorganisms--a new subfamily of chymotrypsin
      proteinases].

PMID- 9612568
TI  - [Structural and functional characteristics of angiotensin converting enzyme].
AB  - The structure and functions in various tissues of angiotensin converting enzyme
      (ACE, peptidyl dipeptidase A), a key enzyme in blood pressure regulation, are
      reviewed. The similarity and differences of two homologous catalytically active N
      and C-domains of the ACE molecule are discussed, and different biological
      functions of these domains are suggested. Natural active single-domain forms of
      ACE are characterized.

PMID- 9612569
TI  - [Proteolytic degradation of hemoglobin in erythrocytes results in formation of
      biologically active peptides].
AB  - The formation of biologically active hemoglobin fragments in human erythrocytes
      was studied. The structures of 33 peptide products of intraerythrocytic
      hemoglobin cleavage were determined. Based on an analysis of these sequences, a
      model of the stepwise degradation of the hemoglobin alpha- and beta-chains was
      suggested. The processes of peptide formation in a cell-free erythrocyte lysate
      system were studied. The involvement of an enzymatic complex of the cell membrane
      fraction was demonstrated. It was found that the cells of a surviving human
      erythrocyte culture secrete short (of 5-20 amino acid residues) peptides, and the
      structures of 36 peptides were determined. The dynamics of peptide secretion was
      investigated, and preliminary data on the energy-dependence of this process were
      obtained. Based on the experimental results, a model describing erythrocytes as
      an endocrine gland was suggested.

PMID- 9612570
TI  - [Structural characteristics providing for high specificity of enteropeptidase].
AB  - The effects of structural modification upon the specificity of enteropeptidase
      were studied. A variation in the unique specificity of the enzyme was shown to be
      the result of an autolysis caused by the enzyme's loss of calcium ions. The
      cleavage sites of the autolysis were determined. A truncated enzyme containing
      the C-terminal fragment of its heavy chain (466-800 residues) and the intact
      light chain were shown to be the products of autolysis. The kinetic parameters of
      the hydrolysis of trypsinogen, a recombinant protein, and a peptide substrate
      with both forms of enteropeptidase were determined. Conditions were found that
      can help regulate the transition of the native enzyme into the truncated form. A
      hypothesis was proposed concerning the autoactivational character of
      proenteropeptidase processing.

PMID- 9612571
TI  - [Thrombin--a regulator of reparative processes in wound healing].
AB  - Thrombin, binding to receptors of the protease activated receptor (PAR) family,
      is involved in wound healing by inducing the reparation processes and regulating
      the activity of mast cells, which secrete mediators of inflammation. Using
      thrombin receptor agonist peptide (TRAP-6) for the activation of rat mast cells,
      effect of several receptors, including PAR-1, on mast cells was demonstrated. It
      was shown that TRAP increases the concentration of Ca2+ in the cytoplasm of mast
      cells and regulates cell degranulation, while releasing nitrogen oxide. Thrombin
      encapsulated in poly(N-vinyl caprolactam)-calcium alginate (PVCL-Ca-Alg) hydrogel
      films promotes wound healing in rats as demonstrated by the acceleration of
      fibroblast proliferation and neovascularization.

PMID- 9612572
TI  - [In vitro coupling of ATP hydrolysis to proteolysis of ATP site mutant forms of
      Lon-proteinase from E.coli].
AB  - In order to identify amino acid residues involved in ATP hydrolysis by
      Escherichia coli protease Lon or participating in the signal transduction from
      the ATPase domain to the proteolytic one, potentially important residues of the
      ATPase domain were substituted using site-directed mutagenesis, and the
      properties of the resulting mutant enzymes were studied. It was found that
      residues K362, T363 (Walker's motif A), and D423 (motif B) are involved in the
      catalysis of ATP hydrolysis. K362 and T363 also participate in the system of
      domain-domain coupling, whereas D423 does not play a significant role in this
      process. Residue D387 is important for ATPase activity; however, it is not a
      catalytically active residue, as was earlier postulated in the literature.
      Residue Y493 is also involved in the signal transduction from the ATPase domain
      to the proteolytic one.

PMID- 9612573
TI  - [Duodenase--a potential activator of cascade of digestive proteases].
AB  - The substrate specificity of duodenase from bovine duodenum mucosa to synthetic
      and natural polypeptides was studied. Amino acid residues preferential for
      duodenase in the P1 and P2 positions of the substrate were determined. It was
      shown that the enzyme is synthesized in epithelial secretory cells of duodenal
      (Brunner's) glands and enters, as part of the secreta, into the lumen of the
      duodenum. The possible role of duodenase as an activator of proenteropeptidase is
      discussed.

PMID- 9612574
TI  - [Synthesis of three- and tetrapeptides catalyzed by subtilisin suspensions in
      organic solvents].
AB  - The behavior of subtilisin 72 in some aprotic solvents (acetonitrile, dioxane,
      and tetrahydrofurane) was studied. The enzyme was shown to be partially soluble
      in tetrahydrofurane, but it is rendered profoundly inactive in this solution. In
      acetonitrile and dioxane, subtilisin formed dilute suspensions whose activities
      were measured after dilution with water. Under these conditions, subtilisin
      suspended in acetonitrile manifested an activity that was an order of magnitude
      higher than that of its dioxane suspension, and this activity continued for a
      long time. Z-Ala-Ala-Leu-pNA was synthesized from Z-Ala-Ala-OCH3 and Leu-pNA
      under the catalysis by dilute suspension of subtilisin in acetonitrile. p
      Nitroanilides of tetrapeptides, Z-Ala-Ala-P1-P'1-pNA, where P1 and P'1 were
      either Leu or Phe, were similarly synthesized in acetonitrile under catalysis by
      dilute subtilisin suspension at [S]:[E] = 10(5):1. p-Nitroanilides of
      tripeptides, Z-Ala-Ala-Leu-pNA, Z-Ala-Ala-Phe-pNA, and Z-Ala-Ala-Phe-NH2, were
      also synthesized in the presence of a concentrated subtilisin suspension at
      [S]:[E] = 10(3):1. It was shown that the increase in enzyme concentration
      resulted in the double coupling of nucleophile, and Z-Ala-Ala-Leu-Leu-pNA, Z-Ala
      Ala-Phe-Phe-pNA, and Z-Ala-Ala-Phe-Phe-NH2 were obtained with 13, 33, and 40%
      yields, respectively. Therefore, such reaction systems can be used for creating
      long hydrophobic peptides whose synthesis in water-organic mixtures is difficult
      due to the poor solubility of starting components in aqueous buffer solutions.

PMID- 9612575
TI  - Two solitudes of complementary and conventional medicine. Where are we going?

PMID- 9612577
TI  - Open dialogue on vasectomies.

PMID- 9612576
TI  - Research data on alendronate: biased opinions?

PMID- 9612578
TI  - Counseling psychiatric patients about drug exposures during pregnancy.
AB  - QUESTIONSeveral of my patients with psychiatric disorders are either planning to
      conceive or are already pregnant. I find it difficult to reassure them about the
      safety of taking medications during pregnancy. How do you deal with such
      situations at Motherisk?ANSWERThese patients should be counseled in an
      unambiguous and consistent manner. They can be referred to the Motherisk Program,
      or Motherisk can fax up-to-date information to their physicians.

PMID- 9612579
TI  - Ophthaproblem. Retinoblastoma.

PMID- 9612580
TI  - Dermacase. Hand-foot-and-mouth disease.

PMID- 9612581
TI  - White lies or fraud?

PMID- 9612582
TI  - Use of a vacuum extractor.

PMID- 9612583
TI  - Does ginkgo help delay dementia?

PMID- 9612584
TI  - Do statin drugs lower the risk of stroke?

PMID- 9612585
TI  - Swords to ploughshares. Gatekeepers turned advocates.

PMID- 9612586
TI  - Chinese herbal medicine and acupuncture. How do patients who consult family
      physicians use these therapies?
AB  - OBJECTIVE: To determine how a population of Chinese patients consulting family
      physicians in Vancouver use traditional Chinese medicine (TCM), specifically
      Chinese herbal medicine and acupuncture. DESIGN: Bilingual survey (English and
      Chinese). SETTING: Four family practices with predominantly Chinese patients in
      metropolitan Vancouver. PARTICIPANTS: The 932 patients or family members who
      visited one of the practices. MAIN OUTCOME MEASURES: Demographic characteristics;
      frequency and reason for visiting a family physician, Chinese herbalist, or
      acupuncturist; choice of practitioner if affected by one of 16 common conditions.
      RESULTS: The study population was mostly Chinese and immigrant to Canada. Chinese
      herbal medicine was currently used by 28% (262/930) of respondents (more than one
      visit in the last year), and another 18% (172/930) were past users. Acupuncture
      was currently used by 7% (64/927) and had been used in the past by another 8%
      (71/927). Use of Chinese herbal medicine varied significantly (P < .01) according
      to age, sex, immigrant status, and ethnicity. Acupuncture use varied
      significantly only by age. The main reasons for consulting Chinese herbalists
      were infection (41%, 157/382), respiratory problems (11%, 42/382), and
      rheumatologic problems (10%, 38/382), whereas acupuncturists were consulted
      almost exclusively for rheumatologic problems (80%, 45/56). CONCLUSIONS: Using
      TCM in conjunction with visiting family physicians was very popular among this
      predominantly Chinese study population. Patients with acute conditions, such as
      influenza, consulted both their family physicians and Chinese herbalists in quick
      succession. On the other hand, those suffering from more chronic conditions, such
      as rheumatologic diseases, were more likely to start using TCM after repeated
      visits to their family physicians.

PMID- 9612587
TI  - Physicians' perspectives on massage therapy.
AB  - OBJECTIVE: To examine the knowledge, opinions, and referral behaviour of family
      physicians with respect to massage therapy and to explore factors associated with
      referral. DESIGN: A random, cross-sectional mailed survey. SETTING: Alberta
      family practices. PARTICIPANTS: Family physicians (n = 300). MAIN OUTCOME
      MEASURES: A self-report survey was developed for the study. This survey contained
      questions about sociodemographic and practice characteristics, perceived
      knowledge of massage therapy, opinions about the usefulness and legislation
      (government regulations) of massage therapy, and referral behaviour. RESULTS:
      Fifty-four percent of physicians (n = 161) completed the questionnaire. Sixty
      eight percent of respondents indicated they had minimal or no knowledge of
      massage therapy. Despite this low level of knowledge, most (83%) believed massage
      therapy was a useful adjunct to their own practice. Moreover, 71% had referred
      patients to massage therapists and most (72%) perceived increasing demand from
      their patients for massage therapy. Approximately half of physicians surveyed
      supported government regulation of massage therapy. CONCLUSIONS: Physicians
      demonstrated a discrepancy between their knowledge of massage therapy and their
      opinions of, and referrals to, the profession. Physicians who referred patients
      to massage therapists generally held more positive opinions and had more
      knowledge of the discipline.

PMID- 9612588
TI  - Factors influencing palliative care. Qualitative study of family physicians'
      practices.
AB  - OBJECTIVE: To examine factors that influence family physicians' decisions to
      practise palliative care. DESIGN: Qualitative method of in-depth interviews.
      SETTING: Southwestern Ontario. PARTICIPANTS: Family physicians who practise
      palliative care on a full-time basis, who practise on a part-time basis, or who
      have retired from active involvement in palliative care. METHOD: Eleven in-depth
      interviews were conducted to explore factors that influence family physicians'
      decisions to practise palliative care and factors that sustain their interest in
      palliative care. All interviews were audiotaped and transcribed verbatim. The
      analysis strategy used a phenomenological approach and occurred concurrently
      rather than sequentially. All interview transcriptions were read independently by
      the researchers, who then compared and combined their analyses. Final analysis
      involved examining all interviews collectively, thus permitting relationships
      between and among central themes to emerge. MAIN OUTCOME FINDINGS: The overriding
      theme was a common philosophy of palliative care focusing on acceptance of death,
      whole person care, compassion, communication, and teamwork. Participants'
      philosophies were shaped by their education and by professional and personal
      experiences. In addition, participants articulated personal and systemic factors
      currently affecting their practice of palliative care. CONCLUSIONS: Participants
      observed that primary care physicians should be responsible for their patients'
      palliative care within the context of interdisciplinary teams. For medical
      students to be knowledgeable and sensitive to the needs of dying patients,
      palliative care should be given higher priority in the curriculum. Finally,
      participants argued compellingly for transferring the philosophy of palliative
      care to the overall practice of medicine.

PMID- 9612589
TI  - Zinc gluconate and the common cold. Review of randomized controlled trials.
AB  - OBJECTIVE: To examine the evidence of seven randomized controlled trials (RCT) on
      the therapeutic effectiveness of zinc gluconate lozenges for treating the common
      cold. DATA SOURCES: Using the MeSH headings common cold and zinc gluconate,
      MEDLINE was searched from 1966 on for all published RCTs evaluating use of zinc
      gluconate for treating the common cold. STUDY SELECTION: For this study, only
      double-blind RCTs were included. SYNTHESIS: Fair evidence suggests that zinc
      gluconate lozenges have a therapeutic effect in treating the common cold.
      Starting therapy with zinc gluconate lozenges within 24 to 48 hours of onset of
      cold symptoms reduces the duration and severity of the cold. Patients must suck
      lozenges every 2 hours while awake during the cold. Minimum effective dose
      appears to be 13.3 mg of elemental zinc per lozenge. Evidence suggests that
      compounds such as citric acid, sorbitol, and mannitol bind the free zinc ion in
      the mouth, and this could account for variations in therapeutic benefit. Bad
      taste and nausea are important side effects of zinc lozenges. CONCLUSION:
      Evidence supports use of zinc gluconate lozenges for reducing the symptoms and
      duration of the common cold, but the side effects, bad taste, and therapeutic
      protocol might limit patient compliance.

PMID- 9612590
TI  - Preparing for rural practice. Enhanced experience for medical students and
      residents.
AB  - PROBLEM ADDRESSED: Recruitment and retention of physicians appropriately trained
      for rural practice in Canada continues to be a serious challenge. We describe
      three integrated educational programs at the University of Alberta that aim to
      increase students' and residents' participation in rural health care and
      encourage them to take up practice in rural areas. OBJECTIVES OF PROGRAM: To
      expand and enrich rural educational experiences at undergraduate and postgraduate
      levels and to supplement family medicine postgraduate education with a third-year
      special-skills program for rural practice. MAIN COMPONENTS OF PROGRAM: Main
      components are sustained, reliable funding from the Government of Alberta for the
      Rural Physician Action Plan; adequate infrastructure to support the program; and
      commitment by university faculty, rural physicians, and communities. CONCLUSION:
      The rural-based educational programs have allowed more than 95% of medical
      students to gain experience in rural areas. The number of family medicine
      residents doing rural rotations has doubled, and the length of experiences in
      rural practice has increased fourfold. The third-year special-skills training for
      rural practice has expanded greatly, and at least 26 of 49 participants have gone
      on to enter rural practice. In more than 30 rural Alberta communities, 56
      physicians have had an important influence on the training of medical students
      and family medicine residents.

PMID- 9612591
TI  - Structured approach to pharmaceutical representatives. Family medicine residency
      program.
AB  - PROBLEM BEING ADDRESSED: Family medicine residents frequently interact with
      pharmaceutical sales representatives (PSRs) during their medical training; the
      literature indicates that these meetings affect future prescribing habits. We
      needed to develop a structured approach to PSR visits because our program did not
      provide residents with a consistent experience in dealing with PSRs. OBJECTIVE OF
      PROGRAM: To develop a structured approach to PSR visits that would permit
      residents to better understand the role of PSRs and to gain more from their
      interactions with PSRs in the future. MAIN COMPONENTS OF PROGRAM: First-year
      family medicine residents at an academic teaching unit in Edmonton were surveyed
      on their knowledge and attitude to PSRs and then given a 1-hour educational
      seminar and five structured visits from PSRs. Following each PSR presentation,
      residents completed an evaluation form and discussed the interaction with their
      preceptors. CONCLUSIONS: We believe that a structured educational program is
      better than a written policy restricting interactions between PSRs and residents
      for providing residents with an understanding of the role of PSRs and making them
      better prepared for future contact.

PMID- 9612592
TI  - Routine administration of vitamin K to newborns. Joint position paper of the
      Canadian Paediatric Society and the Committee on Child and Adolescent Health of
      the College of Family Physicians of Canada.

PMID- 9612593
TI  - Regulation of telomerase activity in normal and malignant human cells.
AB  - In recent years, a particular type of reverse transcriptase termed telomerase has
      attracted much attention because of its potential utility as both a diagnostic
      marker and a therapeutic target in cancer. This enzyme is present in almost all
      cancer, but not in normal cells. Understanding telomerase structure, expression,
      and activity regulation is pivotal for the prospects of using it as a target in
      cancer therapy, with respect to both therapeutic and undesirable side effects.
      This review presents the current state of studies on the regulatory pathways of
      telomerase activity in human cells.

PMID- 9612594
TI  - Interferon and kidney cancer: a promise unfulfilled?

PMID- 9612595
TI  - Radiotherapeutic strategies in the management of clinically localized, "low-risk"
      prostate cancer: selection, results, and the search for answers.

PMID- 9612596
TI  - Early-stage prostate cancer: controversies, confusion, and difficult choices.

PMID- 9612597
TI  - The treatment of metastatic renal cell carcinoma patients with recombinant human
      gamma interferon.
AB  - PURPOSE: Activity has been reported in phase II single-center, open-label studies
      after administration of low-dose recombinant interferon gamma-1b (rIFN-gamma) to
      patients with metastatic renal cell carcinoma, with an overall objective response
      proportion of around 15%. To confirm these data and define the complete response
      rate, we conducted a multicenter open-label trial in which 204 patients with
      metastatic renal cell carcinoma were treated with rIFN-gamma. PATIENTS AND
      METHODS: Two hundred and seven patients (134 males, 73 females, mean age 59) were
      enrolled, and 202 were evaluable. rIFN-gamma, 60: microgram/m2, was administered
      subcutaneously once every 7 days until disease progression. RESULTS: There were
      three (1.5%) complete responses and three (1.5%) partial responses, for an
      overall response proportion of 3% (95% CI: 1.2%, 6.7%). The median response
      duration was 13.3 months (range: 2 to 23 months). The median survival was 13.4
      months (5.5 months to 29.2 months). Three (1%) deaths were observed during the
      course of study; they were considered to be related to progressive metastatic
      renal cell carcinoma. Toxicity was minimal, with 14% of patients experiencing
      grade 3/4 toxicity. The most frequent adverse events were chills (59%), fever
      (58%), asthenia (53%), nausea (29%), and headache (18%). Multivariate analysis
      revealed that younger age, higher performance status, higher hemoglobin, and
      lower LDH were predictive of survival. DISCUSSION: Recombinant interferon gamma
      1b has only minimal efficacy in the treatment of metastatic renal cell carcinoma.
      Pretreatment variables associated with increased survival were male sex, higher
      Karnofsky performance status, higher hemoglobin, and low LDH.

PMID- 9612599
TI  - A comparison of prostate knowledge of African-American and Caucasian men: changes
      from prescreening baseline to postintervention.
AB  - PURPOSE: This study was undertaken to determine if a community screening program
      designed to overcome key barriers (lack of awareness, cost of program, ease of
      access to care) could successfully impact on African-American males' knowledge,
      attitudes, and behaviors regarding prostate cancer screening. The focus of this
      report is knowledge. To date, there are no reported studies that examine
      differences in knowledge from a prescreening baseline to a postintervention level
      for minority participants. PATIENTS AND METHODS: A total of 944 men were enrolled
      in the study in a 20-month period. Prostate screening and education were offered
      as a new service at an existing senior health clinic. In addition, mass
      screenings were offered approximately monthly at various locations in the
      community (including senior community centers, senior apartment complexes, and
      some public housing projects). Screening included both the digital rectal
      examination and the prostate specific antigen test. A brief questionnaire was
      administered during client intake (the pretest) and repeated after the education
      and screening participation (the posttest). Test items targeted three constructs:
      (1) etiology, (2) risk status, and (3) clinical factors. RESULTS: The largest
      difference on pretest scores between the racial groups resulted from clinical
      factor knowledge. African-American men were significantly less likely than
      Caucasian men to correctly identify early symptoms of prostate cancer and the
      basic components of a prostate checkup. Although scores were initially
      significantly lower for African-American participants, these differences were not
      evident after program involvement. There was a significant increase in knowledge
      level for all men when comparing pretest and posttest scores. Significant
      improvement was noted for each test item, with the exception of one key item.
      Even after participation in the program, African-American men were still more
      likely to believe that "pain" was the first symptom of prostate cancer.
      DISCUSSION: An item-by-item analysis revealed that there was only one test item
      in which program participation did not "correct" knowledge. African-American men
      were still more likely to believe that pain was the first symptom that would
      alert them to the presence of cancer. The screening program included information
      (both printed and oral content) that emphasized the importance of routine
      screening to detect cancer at an early stage, because most men would experience
      no symptoms. The only other reported study that examined knowledge documented
      similar findings with respect to an understanding of symptomology. These findings
      can be used to direct or guide the educational component of future screening
      programs that hope to target African-American men.

PMID- 9612598
TI  - Candidates for prostate radioactive seed implantation treated by external beam
      radiotherapy.
AB  - PURPOSE: We report the prostate-specific antigen-based freedom from biochemical
      failure after conventional and three-dimensional conformal external beam
      radiotherapy for patients who would have been candidates for 125I implantation
      monotherapy. MATERIALS AND METHODS: Patients included in the study were required
      to have prostate-specific antigen values < or = 20, T stage < or = 2b, and
      Gleason score sum of 2 to 6. All patients underwent external beam irradiation
      with curative intent and a minimum follow-up from completion of treatment of at
      least 1 year. In addition, all patients had to have pretreatment and follow-up
      prostate-specific antigen measurements and no history of hormonal manipulation,
      orchiectomy, or radical prostatectomy. A total of 187 patients meeting these
      criteria were treated between March 1988 and June 1995, and they form the study
      group for this analysis. Freedom from biochemical failure was defined as prostate
      specific antigen value that failed to be maintained at 1 ng/mL or less or an
      increase in prostate-specific antigen value of 0.5 ng/mL or more in 1 year even
      if prostate-specific antigen value was less than 1 ng/mL. RESULTS: Among the 187
      patients, the median pretreatment prostate-specific antigen value was 7.4 ng/mL
      (0.3-19.9 ng/mL). The median follow-up was 34 months. Twenty-three percent of
      patients had a Gleason score sum of 2 to 4, and 77% had a Gleason score sum of 5
      to 6. Clinical stages were T1 in 33% and T2 in 67%. One hundred twenty-five
      patients were treated by conventional external beam radiotherapy with a median
      dose of 69.5 Gy (60-71 Gy), and 62 patients were treated by three-dimensional
      conformal external beam radiotherapy with a median dose of 76.4 Gy (71.6-87 Gy).
      The overall freedom from biochemical failure was 75% at 4 years. Rates of freedom
      from biochemical failure by pretreatment prostate-specific antigen levels were
      91% for prostate-specific antigen value < or = 4 ng/mL, 65% for prostate-specific
      antigen value > 4 but < or = 10 ng/mL, and 30% for prostate-specific antigen
      value > 10 ng/mL. Pretreatment prostate-specific antigen value was a
      statistically significant prognosticator, with lower values associated with
      favorable freedom from biochemical failure outcome in univariate and multivariate
      analyses. Conventional versus three-dimensional treatment, T1 versus T2 stage,
      and Gleason score sum 2 to 4 versus 5 to 6 did not show statistically significant
      difference in freedom from biochemical failure. CONCLUSIONS: Although our overall
      results after external beam radiotherapy for early-stage prostate cancer patients
      are less favorable than the best results published for 125I implantation
      monotherapy, our results are comparable to those in most other studies with
      implantation monotherapy. This most likely results from selection bias as well as
      our stricter definition of freedom from biochemical failure. In addition, for our
      subset of patients, there was no statistically significant improvement in the 4
      year freedom from biochemical failure with the use of higher doses.

PMID- 9612600
TI  - Survival results among patients with alpha-fetoprotein-positive, unresectable
      hepatocellular carcinoma: analysis of three sequential treatments of the RTOG and
      Johns Hopkins Oncology Center.
AB  - PURPOSE: To analyze the observed therapeutic impact of the post-induction
      components of three treatment programs utilized sequentially between 1983 and
      1991 for patients with unresectable alpha-fetoprotein-positive hepatoma. METHODS:
      Over a 7.5-year period, three treatment regimens were sequentially utilized: (1)
      RTOG 83-19, (2) a Johns Hopkins Oncology Center Institutional Pilot Program, and
      (3) RTOG 88-23. Each treatment program began with an induction phase of external
      beam hepatic irradiation (2100 cGy/7 fractions), with concurrent doses of
      intravenous chemotherapy intended to be radiosensitizing. After induction,
      patients received cycles of one of the following: (1) intravenous doxorubicin and
      5-fluorouracil (5-FU) with or without 131I-polyclonal antiferritin (RTOG 83-19);
      (2) intrahepatic artery cisplatin (Hopkins Institutional Pilot); or (3)
      intrahepatic artery cisplatin with or without 131I-polyclonal antiferritin (RTOG
      88-23). Analysis of survival results was performed with multivariate and Cox
      regression methods. RESULTS: The addition of intravenous 131I-polyclonal
      antiferritin to post-induction cycles of either intravenous doxorubicin and 5-FU
      or intrahepatic artery cisplatin did not enhance survival. Intrahepatic artery
      cisplatin treatment yielded median survival duration of 9.1 months and survival
      at 12 and 24 months of 37% and 9%, respectively. These results were significantly
      superior to those resulting from use of intravenous doxorubicin and 5-FU (P =
      0.0001; median survival duration 3.6 months; 12- and 24-month survival results
      17% and 4%, respectively). A significant survival difference for the cisplatin
      regimen remained even when patients were stratified by previously identified
      prognostic factors and the results were appropriately adjusted. CONCLUSION:
      Patients with unresectable alpha-fetoprotein-positive hepatocellular carcinoma
      experienced improved survival and decreased toxicity when managed with post
      induction cycles of intra-arterial cisplatin as compared with intravenous
      doxorubicin and 5-FU. Intravenous 131I-polyclonal antiferritin did not improve
      survival when added to either post-induction regimen but dramatically increased
      hematologic toxicities.

PMID- 9612601
TI  - Concurrent chemotherapy and radiation for breast conservation treatment of early
      stage breast cancer.
AB  - PURPOSE: The optimal sequencing of chemotherapy and radiation therapy in patients
      with early-stage breast cancer undergoing breast-conservation treatment remains
      controversial. The purpose of this study is to evaluate the outcome of patients
      treated with one specific sequence of concurrent chemoradiation followed by
      additional chemotherapy. METHODS: Between 1977 and 1992, 210 patients with stage
      I and II breast cancer underwent lumpectomy and axillary lymph node dissection
      followed by treatment with concurrent chemotherapy and radiation therapy,
      followed by further chemotherapy. Chemotherapy consisted of two 28-day cycles of
      CF (oral cyclophosphamide, 100 mg/m2 day 1 to 14, and intravenous 5-fluorouracil,
      600 mg/m2 days 1 and 8) during radiation therapy, followed in general by six
      cycles of CMF (CF doses as above plus intravenous methotrexate 40 mg/m2 days 1
      and 8) after the completion of radiation therapy. Fifty patients also received
      hormonal therapy, predominantly tamoxifen. One hundred ten patients had clinical
      T1 lesions, and 100 had T2 lesions. Fifty-three patients were pathologic N0, and
      157 patients were pathologic N1 (123 patients had one to three positive nodes,
      and 34 patients had four or more positive nodes). Median follow-up for node
      negative patients (5.2 years) is shorter than for node-positive patients (7.6
      years). Therefore, outcome is reported at 5 and 10 years for node-positive
      patients but only at 5 years for node-negative patients. RESULTS: For node
      positive patients, outcomes at 5 and 10 years, respectively, were 86% and 70% for
      overall survival, 78% and 67% for no evidence of disease survival, and 82% and
      69% for freedom from distant metastases. For node-negative patients, outcomes at
      5 years were 94% for overall survival, 94% for no evidence of disease survival,
      and 94% for freedom from distant metastases. Pathologic nodal status was
      predictive of outcome after treatment. Local failure in the treated breast was 5%
      at 5 years and 13% at 10 years for all patients. CONCLUSIONS: Concurrent CF with
      radiation therapy followed by six cycles of CMF after radiation therapy results
      in excellent survival, freedom from distant metastases, and local control for
      both node-negative and node-positive patients. This regimen of concurrent
      chemotherapy and radiation therapy is one option for sequencing, and it avoids
      the delays in administration of either modality that are associated with other
      sequencing regimens.

PMID- 9612603
TI  - Antibacterial activity of peritoneal exudate in patients treated with 2 g
      cefotiam for surgical anti-microbial prophylaxis.
AB  - The objective of this study was to investigate the presence of antibacterial
      activity in peritoneal exudate (PE) of patients treated with cefotiam (CFT). CFT
      (2 g) was administered as a 'single-shot' antimicrobial prophylaxis to 6 patients
      at the beginning of colorectal resection. Samples of PE were collected from each
      patient on days 1, 2 and 3 after surgery. CFT was detectable in the samples of
      day 1 for 5 of the 6 patients. The influence of PE on antibacterial activity of
      the antimicrobial drug was evaluated carrying out the MICs of CFT against
      Escherichia coli K-12, E. coli (ATCC 10798), Klebsiella pneumoniae (ATCC 1003),
      Proteus rettgeri (Sanelli) and Staphylococcus aureus (ATCC 29213) with and
      without the addition of PE. The presence of PE enhanced the antimicrobial
      activity of CFT against gram-negative strains, but not against S. aureus (ATCC
      29213). These results suggest the presence of substances in PE that possess
      endogenous antibacterial activity. Thus, antimicrobial activity in PE cannot be
      predicted by evaluating pathogen sensitivity in vitro only.

PMID- 9612602
TI  - Development and characterization of a cytokine-secreting pancreatic
      adenocarcinoma vaccine from primary tumors for use in clinical trials.
AB  - Preclinical studies with murine tumor models have demonstrated that tumor cell
      vaccines engineered to secrete certain cytokines in a paracrine fashion elicit
      systemic immune responses capable of eliminating small amounts of established
      tumor. In particular, tumors that express the cytokine GM-CSF produce potent
      systemic antitumor immune responses against poorly immunogenic murine tumors.
      These results have encouraged the development of paracrine-cytokine secreting
      tumor vaccines for gene therapy of human cancer. GM-CSF recruits professional
      antigen-presenting cells, which in turn activate effector T cells. These findings
      suggest that allogeneic as well as autologous tumor cells can be used as the
      tumor source for developing cancer vaccines. A major obstacle to creating
      genetically modified human allogeneic tumor vaccines is the absence of stable
      cell lines required for efficient gene transfer, because most human tumors
      isolated from primary surgical specimens fail to proliferate in long-term
      culture. We have developed a method for the routine generation of in vitro cell
      lines from primary tumors of the pancreas. This method overcomes the common
      problem of stromal and fibroblast overgrowth that can inhibit the in vitro
      expansion of many histologic types of tumors. In addition, we have analyzed 12 of
      these cell lines for cytokeritin and mutated K-ras expression to demonstrate that
      they derive from the original epithelial tumor tissue. The lines can be
      genetically modified to stably express the cytokine GM-CSF. These methods should
      be helpful to investigators attempting to establish cell lines from other
      histologic tumor types for the development of allogeneic genetically modified
      tumor vaccines.

PMID- 9612604
TI  - In vitro and in vivo antibacterial activities of S-1090, a new oral
      cephalosporin, in the fields of obstetrics and gynecology.
AB  - S-1090 is a new synthetic, nonesterified, oral cephalosporin with a broad
      spectrum of antibacterial activity. The activities of S-1090 against the
      causative organisms in the fields of obstetrics and gynecology are superior to
      those of the currently prescribed oral cephems, cefdinir, cefpodoxime, and
      cefaclor. The in vivo efficacy of S-1090 was evaluated using uterine endometritis
      of model rats. The accumulation of neutrophils in the uterus in the S-1090
      treated group was milder than that in the nontreated group, and the same was true
      for the bacteriological response. S-1090 is a promising oral cephalosporin
      antibiotic for the treatment of infections in the fields of obstetrics and
      gynecology.

PMID- 9612606
TI  - Antibiotic susceptibility of Stenotrophomonas (Xanthomonas) maltophilia:
      comparative (NCCLS criteria) evaluation of antimicrobial drugs with the agar
      dilution and the agar disk diffusion (Bauer-Kirby) tests.
AB  - Ninety-six clinical isolates of Stenotrophomonas maltophilia were examined with
      the agar dilution method for susceptibility to 19 antimicrobial drugs.
      Doxycycline, cotrimoxazole, timentin, ofloxacin, fosfomycin, and piperacillin +
      tazobactam, in that order, inhibited the majority of strains. All isolates were
      resistant to nitrofurantoin. Concurrent disk susceptibility (Bauer-Kirby method)
      testing, using currently valid NCCLS interpretative criteria for Pseudomonas
      aeruginosa, uncovered a significant incidence of very major (category I), major
      (category II), and minor (categories III and IV) discrepancies for
      aminoglycosides, cephalosporins, chloramphenicol, and piperacillin + tazobactam
      and ticarcillin + clavulanic acid. Therefore, new interpretative criteria
      indicative of intermediate (I) susceptibility of S. maltophilia to these various
      antibiotics were proposed. In addition, new intermediate susceptibility criteria
      were proposed for the two beta-lactam-beta-lactamase inhibitor combinations. It
      was recommended to exclude ciprofloxacin from test batteries against this
      microorganism due to the wide scatter of minimal inhibitory concentration values
      and diameters of inhibition zones; the same was true for polymyxin B. It is hoped
      that the proposed modified, species-specific criteria will improve the clinical
      utility of laboratory-generated disk antibiograms with respect to the inherently
      multiple antibiotic-resistant, opportunistic pathogen S. maltophilia.

PMID- 9612605
TI  - In vitro bactericidal activities and morphologic changes in Escherichia coli and
      Bacteroides fragilis by cephalosporins.
AB  - Polymicrobial infections with aerobes and anaerobes are common in pelvic
      inflammatory diseases. New parenteral cephalosporins have been widely used
      against those infections. We investigated in vitro morphologic changes and
      bactericidal activities on Escherichia coli and Bacteroides fragilis by
      cephalosporins; cefluprenam (CFLP), ceftazidime (CAZ) or cefotaxime (CTX). CFLP
      induced morphologic changes (filamentation) and bactericidal activities on E.
      coli and B. fragilis. Morphologic changes were observed by electron microscope.
      The filamentation induced by CFLP was time and concentration dependent. The
      bactericidal activity of CFLP against E. coli was almost equal to those of CAZ
      and CTX. The bactericidal activity of CTX against B. fragilis was superior to
      those of CFLP and CAZ. These results suggest that there are characteristic
      aspects in each cephalosporin.

PMID- 9612608
TI  - Interaction between levofloxacin and vancomycin in rats--study of serum and organ
      levels.
AB  - The changes of pharmacokinetic parameters when levofloxacin (LVFX) and vancomycin
      (VCM) were administered concomitantly were studied in rats. There was an increase
      in the AUC and Tmax of LVFX with concomitant administration, but no effect on
      Cmax. There was also an increase in the AUC and T1/2 of VCM with concomitant
      administration, while Vd was reduced. Concomitant administration had no effect on
      the correlation between the serum and hepatic tissue concentrations of LVFX, but
      it markedly decreased the correlation between the serum and renal tissue
      concentrations of VCM. BUN was increased at 8 h after the administration of VCM.
      There have been reports that renal dysfunction can be caused by VCM, and our
      findings suggested that concomitant administration of LVFX and VCM must be
      performed with caution.

PMID- 9612607
TI  - Effect of zidovudine therapy in patients with HIV infection on endogenous
      interferon plasma levels and the hepatic cytochrome P450 enzyme system.
AB  - In this study, we wanted to investigate if there are differences in endogenous
      interferon (IFN) plasma levels in patients with different stages of HIV
      infections before and after therapy with zidovudine (ZDV) and determined the
      influence of ZDV therapy on the hepatic monooxygenase system by measuring the
      antipyrine pharmacokinetics. Therefore we investigated the endogenous IFN plasma
      levels in patients with asymptomatic HIV infection (CDC/WHO A1, n = 10) and
      patients with AIDS (CDC/WHO C3, n = 10). In AIDS plasma IFN-alpha and IFN-gamma
      levels are elevated (15.6 +/- 5.8 U/ml; 2.1 +/- 0.7 U/ml) compared to patients
      with an asymptomatic HIV infection (6.1 +/- 3.3 U/ml; 0.6 +/- 0.3 U/ml). The
      antipyrine clearance was significantly reduced in the group of AIDS patients
      (43.1 +/- 7.2 ml/min compared to 56.4 +/- 8.7 ml/min). In a second study with 11
      patients in stage CDC/WHO A1/2 and CDC/ WHO B/C3 each, we studied the effect of a
      14-day administration of ZDV on the endogenous plasma IFN levels and the CYP450
      enzyme activity using the antipyrine pharmacokinetics as a parameter. We
      investigated the antipyrine clearance, clearance to metabolite and half-life by
      using HPLC. IFNs were measured by RIA or ELISA, respectively. In the first group
      no significant alterations of antipyrine kinetics or plasma IFN levels were
      observed after treatment with ZDV. In contrast to these results, we found a
      significant decrease in IFN-alpha and IFN-gamma (19.8 +/- 3.6 U/ml, 4.6 +/- 1.5
      U/ml before; 7.9 +/- 2.6 U/ml, 1.9 +/- 1.3 U/ml after administration of ZDV), a
      decrease in antipyrine half-life, an elevation of the antipyrine clearance (49.8
      +/- 15.7 ml/min, 57.3 +/- 13.7 ml/min) and an elevation of the clearances to
      metabolite.

PMID- 9612609
TI  - The in vitro effect of macrolides on the interaction of human polymorphonuclear
      leukocytes with Pseudomonas aeruginosa in biofilm.
AB  - The in vitro effect of macrolides at concentrations below the minimum inhibitory
      concentration (sub-MIC) on the interaction between Pseudomonas aeruginosa biofilm
      and human polymorphonuclear leukocytes (PMNs) was investigated by using a
      chemiluminescence assay. The PMN response to either mucoid or nonmucoid P.
      aeruginosa biofilm was strongly reduced compared with the response to planktonic
      bacteria (p < 0.01, p < 0.001, respectively). When biofilms were treated with
      erythromycin, clarithromycin, roxithromycin and azithromycin prior to incubation
      with PMNs, the chemiluminescence response was markedly enhanced as compared to
      untreated controls, and a dose-dependent effect was noted over the range of sub
      MIC concentrations studied. In general, macrolides appeared to be slightly more
      active against mucoid biofilm. Azithromycin was shown to be the most active
      macrolide against P. aeruginosa biofilms. However, the treatment with sub-MICs of
      rokitamycin did not have any effect. On the other hand, treatment of planktonic
      bacteria with macrolides before being exposed to the PMNs did not affect the
      chemiluminescence response as compared to untreated controls. These findings
      suggest that macrolides inhibiting the biofilm formation of P. aeruginosa may
      facilitate the phagocytosis of bacteria by PMNs.

PMID- 9612610
TI  - Inhibition of glycolysis and respiration of sarcoma-180 cells by echitamine
      chloride.
AB  - Malignant tumors are known to exhibit high rates of glycolytic activity leading
      to high production of lactic acid. Hence, neoplastic cells have elevated activity
      of enzymes responsible for glycolysis. Echitamine chloride, an indole alkaloid
      extracted from the bark of Alstonia scholaris, has been reported to have a highly
      promising anticancer activity against fibrosarcoma in rats. In the present study,
      the effect of echitamine chloride on energy metabolism of S-180 cells is
      investigated to have a better understanding on the mode of action of echitamine
      chloride. The effect of echitamine chloride on the mitochondrial and cellular
      respiration of S-180 cells was studied. Also, the effects on glucose utilization,
      pyruvate utilization and lactate formation were studied on whole S-180 cells and
      S-180 cell-free homogenate. The levels of glycolytic enzymes such as hexokinase
      and lactate dehydrogenase were estimated in which particular emphasis has been
      laid on hexokinase which occurs both in cytosolic and particulate forms in
      neoplastic cells. Hence the differential effect of echitamine chloride on the
      levels of total, cytosolic and particulate hexokinase has been investigated. In
      conclusion, echitamine chloride affects both cellular and mitochondrial
      respiration, leading to reduction of the cellular energy pool and thereby
      resulting in the loss of viability of S-180 cells.

PMID- 9612611
TI  - Role of fluconazole in the management of AIDS-related cryptococcosis, according
      to daily dosing.
AB  - No unanimous consent has been reached about treatment guidelines of
      cryptococcosis in the setting of AIDS, as well as about optimal fluconazole
      dosing in both initial and suppressive therapy. In order to evaluate the
      relationship between fluconazole dosing and clinical and microbiological outcome
      of AIDS-related cryptococcosis, a retrospective study was carried out on 30
      consecutive patients. Among the 12 subjects treated with fluconazole doses < 400
      mg/day, an unfavorable course was significantly more frequent (early mortality,
      poor clinical and microbiological response, appearance of early relapses)
      compared with the 18 patients who received daily doses > or = 400 mg, while no
      differences were observed between the two treatment groups according to known
      risk factors for a poor prognosis. When assessing maintenance treatment (22
      evaluable cases), the 15 patients receiving oral fluconazole at doses < 200
      mg/day showed earlier disease relapse and mortality as opposed to the 7
      individuals treated with high-dose fluconazole (> or = 200 mg/day), in the
      absence of significantly different risk factors for disease recurrence. Our
      experience pointed out a significant difference in clinical activity of
      fluconazole in AIDS-related cryptococcosis according to its daily dosing, and
      suggested 400 and 200 mg as the threshold daily dose for an effective initial and
      suppressive therapy, respectively, since the probability of treatment failure
      seemed greater with low-dose drug administration, after controlling data for
      prognostic markers of disease severity. Controlled studies are warranted,
      comparing high-dose fluconazole with standard regimens containing amphotericin B
      in the treatment of AIDS-associated cryptococcosis, and identifying the best
      fluconazole dosing for both acute-phase and maintenance treatment.

PMID- 9612612
TI  - [Research organization].

PMID- 9612613
TI  - [Clinimetry (clinical studies)--an evaluation].
AB  - Clinical research in surgery is criticized now and then throughout the world
      because of its deficits in controlled clinical trials, the reduced spectrum of
      its clinical study types, and its methodological flaws. German surgery, however,
      has always shown reasonable standing in such areas of conflict by following a
      separate path: integration of clinimetric and biomedical research, Europeanizing
      clinical trials, clinical research in quality management and clinical practice
      guidelines, and installation of social psychology as basic science into outcome
      research. This separate path--in contrast to surgery in the U.S.--should, indeed,
      be followed insistently.

PMID- 9612614
TI  - [Microcirculation research in experimental surgery].
AB  - The microcirculation is the organ that provides the direct link between blood and
      tissue, and thereby between the whole organism and the single cell. Modern
      microcirculation research in experimental surgery is characterized by the use of
      high-resolution video fluorescence microscopy and quantitative computer-assisted
      image analysis coupled with the techniques of molecular biology and transgenic or
      knockout gene technology. These advances should improve knowledge about
      surgically relevant physiologic and pathophysiologic phenomena at the interface
      between blood and tissues and help us to understand the initial molecular
      mechanisms leading to organ dysfunction following inflammation, ischemia
      reperfusion, and transplantation.

PMID- 9612615
TI  - [Molecular cell biology--basis for new diagnostic and therapeutic approaches in
      surgical oncology].
AB  - In the past two decades increasing research efforts have focused on the molecular
      biology of the cell. In the beginning, these research activities were purely
      academic without any direct clinical relation. A series of important discoveries,
      initiated particularly by the unravelling of the genetic code and the discovery
      of the molecular basis of gene expression and genetics, the subsequent
      identification of oncogenes and tumor suppressor genes and finally the
      description of major mechanisms which induce genetic instability in cells, now
      indicate the way to many new diagnostic and therapeutic strategies. In surgical
      oncology, these attempts are yielding the first clinical consequences. Basic
      aspects of molecular cell biology as far as they are relevant for surgical
      oncologists are discussed.

PMID- 9612616
TI  - [Multimodal therapy of tumors of the upper gastrointestinal tract].
AB  - Adjuvant and neoadjuvant therapeutic principles have in recent years received
      increasing attention in the management of patients with carcinoma of the upper
      gastrointestinal tract. A series of randomized prospective trials has
      demonstrated that adjuvant postoperative radiation or chemotherapy does not
      result in a convincing survival advantage after complete tumor resection in
      gastric or esophageal cancer. The available data on the role of neoadjuvant
      preoperative therapy in these patients as yet permit no conclusion. While
      neoadjuvant therapy may reduce the tumor mass in a substantial portion of
      patients, a series of randomized controlled trials has shown that, compared to
      primary resection, a multimodal approach does not result in a survival benefit in
      patients with loco-regional, i.e. potentially resectable, tumors. In contrast, in
      patients with locally advanced tumors, i.e. tumors for which complete removal
      with primary surgery appears unlikely, neoadjuvant therapy increases the chance
      for complete tumor resection on subsequent surgery. However, only patients with
      objective histopathologic response to preoperative therapy appear to benefit from
      this approach. Compared to preoperative chemotherapy alone, combined radio
      chemotherapy increases the rate of response, particularly in squamous cell
      esophageal cancer, but may also increase postoperative morbidity and mortality.
      Neoadjuvant therapy should therefore currently only be performed in experienced
      centers within the context of prospective clinical trials. The identification of
      factors that would allow prediction of response to neoadjuvant or adjuvant
      therapy is the focus of ongoing studies.

PMID- 9612617
TI  - [Combination therapy in oncology--hepatocellular carcinoma].
AB  - Hepatocellular carcinoma (HCC) is being diagnosed with increasing frequency in
      the Western world as a consequence of the hepatitis C epidemia. Multimodal
      therapy is now the only effective treatment option to offer a chance of complete
      tumor control in HCC. Liver transplantation and liver resection, including the
      selection criteria and patient evaluation, are discussed. The benefits and
      complications of transarterial chemoembolization and cryotherapy are also
      reviewed. Liver transplantation is now thought to offer the best treatment option
      in early HCC and should be regarded as the first line of treatment in selected
      patients.

PMID- 9612618
TI  - [Combination therapy in oncology (multimodal treatment) in pancreatic tumors].
AB  - The majority of patients with pancreatic cancer have systemic disease already at
      diagnosis, and nearly all patients will develop recurrence following radical
      resection. Thus, surgical treatment alone is insufficient. The paper focuses on
      adjuvant multimodal treatment and reviews the current status of pre- and
      postoperative chemoradiation, intraoperative radiotherapy (IORT), adjuvant
      chemotherapy, and regional infusion therapy. Studies in this area are hampered by
      often being non-randomized and with too few patients included. Overall there
      presently is no adjuvant multimodal treatment which can be suggested for routine
      use. However, two ongoing prospective randomized studies (ESPAC-1 and an EORTC
      study) will have enough statistical power to give reliable information on the
      topic. It is hoped that these and other studies will form the basis for further
      proper clinical trials on multimodal treatment in pancreatic cancer with the aim
      at long last to improve the extremely poor survival in these patients.

PMID- 9612619
TI  - [Multimodal therapy of colon carcinoma].
AB  - A large variety of immunological and cytotoxic adjuvant treatment concepts and
      application routes have been observed to be effective in colon cancer by
      randomized trials during the past three decades. Presently adjuvant 5
      fluorouracil based chemotherapy is favoured for patients with lymph node
      metastases (UICC stage III), since this treatment was associated with a 5-10%
      increase in 5-year survival. Uncertainty persists regarding the optimal use of
      adjuvant treatment, since marked differences in prognosis have been recognized
      within stage III and because the impact of surgical treatment on long-term
      survival has not been thoroughly controlled for in past trials. Current and
      future studies will have to determine precisely which patients will benefit most
      from adjuvant treatment and which combination of surgical and adjuvant treatment
      will be most effective.

PMID- 9612620
TI  - [Multimodal therapy of rectal carcinoma].
AB  - Multimodal therapy for rectal carcinoma is--in contrast to colon cancer--largely
      based on adjuvant or neoadjuvant radiotherapy. Although radiotherapy reduces
      local recurrence rates, overall survival is hardly improved, while on the other
      hand specific complications of radiotherapy are recognized. Extended neoadjuvant
      treatment concepts including chemotherapy may improve long-term outcome, but to
      date this has not been demonstrated conclusively by randomized trials. New
      developments include intraoperative radiotherapy and the combination of
      hyperthermia with radiochemotherapy. Initial results from randomized studies are
      promising, but require confirmation by larger trials. At the same time the
      importance of optimal surgical treatment has been recognized as a prerequisite
      for favourable long-term results. Since this aspect has not received due
      attention in past protocols the optimal combination of surgery with other
      modalities and their time sequence cannot be determined presently.

PMID- 9612621
TI  - [Strategy for multimodal therapy of soft tissue sarcomas of the trunk and
      extremities].
AB  - The aim of surgical therapy for soft tissue sarcoma is local tumor control with
      the best possible functional result. Only small, superficial, well-differentiated
      or strictly intracompartmental lesions should be treated by surgery alone. In all
      other cases, especially for recurrent lesions, multimodality treatment strategies
      should be applied. For locally advanced lesions, neoadjuvant therapy can achieve
      tumor response. Aside from systemic chemotherapy and preoperative radiation
      therapy, isolated limb perfusion with tumor necrosis factor and melphalan can aid
      local control, and thus enable limb-sparing resection. The application of
      adjuvant systemc chemotherapy must be further investigated in prospective trials
      before a general recommendation can be given. If the patient has distant
      metastases, decisions regarding treatment of the local lesion must take into
      account quality-of-life aspects. Should complete resection not be possible,
      multimodality strategies may be able to control the tumor for a longer period.

PMID- 9612622
TI  - [Managed care--an example for future structural developments in health care.
      Reflections on a informational visit on direction and administration of medical
      centers in east USA].
AB  - While the different national health systems merge structurally, cost expansion in
      health care is a global challenge. Structural reforms have been developed during
      recent years in the USA which can be summarized as "managed care". They are
      characterized by the evolution of an economically orientated system, in which
      units of medical therapy are generally handled like conventional economically
      goods. In managed-care models, patients are deliberately directed to the most
      economic forms of therapy. The spectrum of medical interventions as well as
      diagnostic or therapeutic patterns are predefined by a system of contracted
      guidelines, which lead to a standardization of processes. Financing and medical
      executive responsibilities fuse. The autonomy of medical decisions is clearly
      reduced to enforce and integrated and economically oriented steering of the
      health system. Leadership is no longer primarily confined to doctors or
      scientists. It is progressively shifting to financing institutions, managing
      directors or insurance companies. Structural changes currently are expanding
      rapidly in the U.S. and have meanwhile led to marked regional reductions of
      medical costs. Nevertheless, the US model is still far more expensive compared to
      the German system. Historical development, current concepts of US-managed care,
      its potential influence and general applicability to the German situation are
      discussed in an overview.

PMID- 9612623
TI  - [Technique and rationale of lymph node dissection in bronchial carcinoma].
AB  - Any operation for lung cancer that is planned as curative includes dissection of
      the lymph nodes in the mediastinum in order to allow correct staging of the
      disease. It is well known that ipsilateral lymph node metastases (N2) mean a poor
      prognosis. Since most patients with this finding die from metastatic tumor
      progression within 3 years after the operation, it can be assumed that positive
      findings in the mediastinal lymph nodes represent generalization of the cancer.
      Therefore, the probability of a therapeutic effect from more radical removal of
      lymph nodes in the mediastinum is rather low. On the other hand, it is justified
      to apply and evaluate additional systemic treatment in these tumor stages.

PMID- 9612624
TI  - [Puncture tracheostomy versus translaryngeal tracheostomy. A prospective
      randomized study of 50 intensive care patients].
AB  - Percutaneous dilatational tracheostomy (PT) and translaryngeal tracheostomy (TLT)
      are relatively new minimally invasive methods for critically ill patients. To
      compare the perioperative procedural safety we analyzed the severity of
      perioperative blood gas changes in a prospective randomized clinical study in 50
      patients (34 men, 16 women; age 18-84 years). Additionally, early complications
      were documented. Twenty-five PTs and 25 TLTs were performed under tracheoscopic
      guidance. Perioperative hypoxia did not occur in either group; however, a
      decrease of PaO2 of more than 50 mmHg was noticed in nine patients during TLT
      versus three patients with PT (P = 0.051). The mean increase of PaCO2 was
      significantly higher in the TLT-group (5.2 +/- 6.7 vs 11.6 +/- 8.4 mmHg; P <
      0.01). In the PT group no perioperative complications arose; in the TLT group one
      procedure was not successful and had to be converted to a PT. Postoperatively,
      one premature decannulation (PT group) and one bleeding (TLT group) were noticed.
      PT and TLT are safe methods. Early complications are rare in experienced hands.
      TLT tends to cause relevant hypercarbia and should therefore be restricted to
      patients without special risks.

PMID- 9612625
TI  - [The physician's responsibility for confidentiality in the hospital].

PMID- 9612626
TI  - [Millions of old cost burdens. The time bomb of overdue drug budgets].

PMID- 9612627
TI  - [Invitation for joining the Endoprosthesis Register Organization e. V. Gottingen
      in Chirurg (BCDC) no. 11/1997].

PMID- 9612628
TI  - [Conversion of experimental research findings to treatment of acute
      pancreatitis].
AB  - Performing prospective, randomized controlled studies in patients with severe
      acute pancreatitis is limited due to low disease incidence and organizational and
      financial problems. Thus, animal models simulating the clinical condition have
      been developed for testing innovative therapeutic procedures. Despite objections
      regarding the applicability of data obtained from animal experiments to clinical
      practice, the experience gained from these studies could not only be used in
      clinical study proposals but also, in part, directly influenced the clinical
      management of acute pancreatitis. This is illustrated by studies regarding the
      influence of contrast medium, isovolemic hemodilution and various antibiotics.

PMID- 9612629
TI  - [Effect of the surgeon on treatment quality in acute appendicitis].
AB  - The quality of the surgical therapy in cases of acute appendicitis is influenced
      by the rate of perforating appendicitis, the rate of bland appendicitis and the
      perioperative morbidity. During a prospective follow-up 271 patients were treated
      at our department between 1 April 1993 and 30 July 1996. The rate of perforating
      appendicitis was 3.7%, and that of bland appendicitis was 19.6%. The rate of
      perforating appendicitis did not differ significantly according surgeon, who
      decided to operate. However, the number of patients with bland appendicitis did
      differ significantly among different operators. There were also significant
      differences in the rate of wound infections. No correlation was found between the
      rates of perforating and bland appendicitis was not found. In summary the
      operator affects the quality of the surgical treatment in cases of suspected
      appendicitis by differences in the timing and performance of the surgical
      procedure.

PMID- 9612630
TI  - [Hydrosonography as an alternative or supplement to endosonography in stomach
      carcinoma].
AB  - Transabdominal ultrasound in the hydrotechnique (hydrosonography) was compared
      with endosonography for the locoregional staging of gastric cancer. For this
      purpose 52 consecutive patients were examined by endosonography (7.5 and 12 MHz)
      and hydrosonography (3.75 MHz). Forty-nine of the 52 tumors could be examined by
      endosonography and 41 by hydrosonography. The T-staging accuracy rate of
      endosonography was 74% and 46% for hydrosonography. Carcinoma of the cardia are
      often classified as uT3 and hT3 preoperatively and pT2 postoperatively due to
      infiltration of the subserosal fat. The N-staging accuracy rate of endosonography
      was 86% and 61% for hydrosonography. Based on these results, transabdominal
      ultrasound in the hydrotechnique (hydrosonography) cannot replace endosonography
      in gastric cancer staging. However, when performed in conjunction with
      conventional ultrasound, hydrosonography provides useful information about the
      local tumor stage, especially in cases of advanced and stenotic tumors.

PMID- 9612631
TI  - [Prognostic factors in perforating diverticulitis of the large intestine].
AB  - Morbidity and mortality after emergency procedures in 105 patients with
      perforated colonic diverticulitis were evaluated in a retrospective study. In
      different stages of diverticulitis (Hinchey classification: I, 8.6%; II, 14.3%;
      III, 57.1%; IV, 20.0%) mortality was 12.4%. Preoperative sepsis syndrome with
      leucopenia and disturbed liver function, cardiac risk factors and obesity were
      independent prognostic factors in multiple logistic regression. Accompanied by
      immunosuppression the mortality rate remarkably increased to 33%. The stage of
      peritonitis showed no influence on the prognosis. In multivariate analysis,
      surgical procedure (primary resection 12.4%. Hartmann's procedure 61.9%, non
      resection procedures 25.7%) showed influence only on increased general
      complications.

PMID- 9612632
TI  - [Indications and follow-up of total pelvic exenteration].
AB  - From 1988 to 1996 we performed 18 total pelvic exenterations in patients with an
      average age of 59.8 years who could be followed up for a mean 29.8 months. In 10
      cases a recurrent tumor of the pelvic viscera and 7 times a primary carcinoma of
      the rectum, bladder or prostate were treated. In 1 patient a radiogenic fistula
      led to this operation. Intestinal continuity could be reconstructed in 7 cases.
      Following cystectomy, urinary diversion was accomplished in half of the cases by
      an ileal conduit. Due to septic multiorgan failure 2 patients died
      postoperatively (hospital mortality rate 11%). In 82% a complete resection (R0)
      was possible. Subsequently 5 patients (29%) developed tumor recurrence. Distant
      metastases were observed in 3 patients, 8-9 months after surgery. So far 10
      further patients have died. Their mean survival time was 28.9 months (range 5-99
      months). The remaining 6 patients are still alive between 22 and 36 months
      postoperatively. Despite the extent of this kind of major surgery, which also
      requires multidisciplinary cooperation, and the psychosocial problems resulting
      from two permanent stomas, total pelvic exenteration should be regarded as an
      adequate alternative in the treatment plan in selected patients with locally
      advanced or recurrent pelvic disease.

PMID- 9612633
TI  - [Evacuation defecography and defecoflometry in diagnosis of chronic constipation.
      A prospective comparative study of 49 patients].
AB  - Chronic constipation can be divided in two large groups: slow-transit
      constipation, caused by pathological intestinal transit, and obstructive
      defecation disorder, caused by pelvic and rectal wall abnormalities.
      Videodefecography and defecoflowmetry are methods used to study dynamic
      evacuation of the rectum. Videodefecography also enables visual estimation of
      rectal evacuation. Defecoflowmetry allows analysis of anal and rectal pressures.
      Within this prospective study we utilized and compared these methods in 19
      patients with slow transit and 30 patients with obstructive disease. In patients
      with slow transit, both investigations demonstrated a significantly higher
      defecation rate than in obstructive defecation disorder (slow transit:
      defecoflowmetry 65%, videodefecography 80%; obstructive defecation disorder: 50%
      and 58%). The evacuation time was pathologically prolonged in both types of
      constipation, with a range of 43-55 s. Rectoceles are demonstrated in 94% of
      cases with slow transit and in 72% with obstructive defecation disorder. Also, we
      often found obstructive components in slow-transit constipation patients. Normal
      defecography or defecoflowmetry can rule out obstructive defecation disorder. We
      conclude that videodefecography and defecoflowmetry are important items in the
      complex diagnostic regimen needed in evaluation of chronic constipation.

PMID- 9612634
TI  - [The status of perioperative pain therapy in Germany. Results of a
      representative, anonymous survey of 1,000 surgical clinic. Pain Study Group].
AB  - To evaluate the status of perioperative pain management we mailed a anonymous
      postal survey to all 2,254 surgical departments in Germany. We received answers
      from 1,000 clinics (44.4%) which were representative related to their regional
      distribution. We asked the responsible surgeons to report their organizational
      structure and responsibilities for treating pain patients, the significance of
      the problem, their methods of measuring pain, and the usage of different
      analgesic drugs and methods. In 47% the surgeon and the anesthesist together had
      responsibility for adequate postoperative pain treatment; in 33% and 14%,
      respectively, it was the surgeon and anesthesist alone. Only 41% knew the
      interdisciplinary statement on pain therapy of the Professional Societies of
      German Surgeons and Anaesthesists from 1992. Although the importance of
      postoperative pain is globally acknowledged, only 19.1% of all departments had a
      written concept for pain treatment. Pain was measured in only 11% of the clinics
      mainly by using the visual analogue scale. Most surgeons relieve pain solely with
      systemic drugs. Regional analgesia was used by 18% only 51% of the surgeons
      decide on the choice and dosage of analgesic therapy on the ward; 33% admit that
      pain therapy often starts after complaints of the patient. 70% of all surgeons
      never participated in a congress on pain. We conclude that postoperative pain
      management in most German surgical departments still lacks effectiveness,
      adequacy, and organizational and scientific background.

PMID- 9612635
TI  - [Laparoscopic 2/3 resection of the stomach with intracorporal Roux-en-Y
      anastomosis].
AB  - In a patient with recurrent ulcer disease under medication, which was complicated
      by episodes of bleeding, a laparoscopic partial gastric resection with
      intracorporal Roux-en-Y anastomosis was performed. The operation was completed
      within 3 h with blood loss < 10 ml. The postoperative hospital stay of 6 days was
      uncomplicated as was the further follow-up (2 months so far). This operation and
      the study of results published in the literature showed us that a gastric
      resection can certainly be performed laparoscopically in the appropriate patient.

PMID- 9612636
TI  - [Inflammatory esophageal stenosis with intramural pseudodiverticulosis of the
      esophagus].
AB  - Esophageal intramural pseudodiverticulosis is a very rare disease with unknown
      etiology, which especially affects male patients between 45 and 65 years. This
      disease is characterized by dilatation of the esophageal submucosal glands and
      their outlets. Stenosis caused by esophagitis due to intramural
      pseudodiverticulosis is found in most of the known patients. All patients
      presented with dysphagia, usually of long duration. The characteristic
      radiographic appearance is numerous intramural esophageal contrast-filled
      diverticulosis-like pouches--4 mm in depth.

PMID- 9612637
TI  - [Perforation into the heart--a rare complication of stomach ulcer in hiatal
      hernia].
AB  - Perforation into the heart is a rare ulcer complication in a hiatal hernia.
      Because of the massive bleeding, medical help is often in vain. The case of a 73
      year-old patient reported by our department confirms this. Endoscopic treatment
      was not possible because of the extraordinary amount of blood in the stomach, and
      the high intraoperative blood loss was lethal. If gastric ulcers occur in upper
      regions of the stomach, the possibility of the presence of an paraesophageal
      hernia and elective surgical treatment must be considered.

PMID- 9612638
TI  - [Unusual coincidence of partially active endocrine tumors].
AB  - We report on a female patient who developed five different tumors between the age
      of 53 and 62 years. The following tumors were diagnosed, three of which showed
      endocrine activity: uterine myoma; hemangiopericytoma of the meninges; pleural
      mesothelioma; preperitoneal leiomyoma; medullary carcinoma of the thyroid
      (sporadic form) in a hyperthyroid goiter. Coexistence of hyperthyroidism and
      medullary carcinoma of the thyroid is rare. Paraneoplastically induced
      hypoglycemia--in this patient induced by the pleural mesothelioma and less by the
      preperitoneal leiomyoma--is of similarly infrequent occurrence. Tumors of
      epithelial or mesenchymal origin may cause hypoglycemia as a result of peptide
      secretion, exerting an insulin-like effect. The detection of IGF-I and IGF-II in
      the serum confirms the diagnosis. Insulinoma can be differentiated by the absence
      of hyperinsulinemia.

PMID- 9612639
TI  - [Evaluation of qualification regulations for medical faculties of German
      universities and recommendations for standardization].
AB  - The original reason for using the German "Habilitation" degree to mean that a
      candidade had qualified and could conduct research and teach at a university is
      no longer really valid, as this is being threatened by its importance to further
      careers. Medical faculties must discuss how this development can be curtailed. In
      order to check the current situation, the Habilitation degree systems of 36
      medical faculties of German universities were compared with the aid of a scoring
      system. They differed dramatically. Conformity existed only in the demand for a
      doctoral dissertation, scientific publications and a lecture on approval.
      Concerning other criteria for qualification there was decreasing consensus in the
      following order: Habilitation thesis, commitment to teaching, further
      professional education, participation in congresses, inaugural lecture,
      qualification to teach, scientific activity, broad background in the discipline,
      and introduction to the faculty. Application of the scoring system with a maximum
      of 33 score points resulted in a mean value of 15.2 points and a range from 6 to
      29 points. A significant decrease in the score values occurred with increasing
      age of the Habilitation degree (P = 0.002). Even if scoring systems are ambiguous
      and unfair, our analysis revealed serious differences in the quality of the
      Habilitation degree. Presuming that the German Habilitation degree should be
      maintained as a high-level qualification, we developed proposals that might be
      used to standardize this academic examination.

PMID- 9612640
TI  - [Surgery of inguinal hernia].

PMID- 9612641
TI  - [Intraoperative cholangiography as a routine method?].

PMID- 9612642
TI  - [Prevention of thromboembolism in minimal invasive interventions and brief
      inpatient treatment].

PMID- 9612643
TI  - [Stoma therapy. Management of ileostomy and colostomy patients].

PMID- 9612644
TI  - [Surgical treatment of stomach cancer].

PMID- 9612645
TI  - [Choice of the right surgical treatment for gastric adenocarcinoma].
AB  - In order to choose the optimal for gastric cancer patients it is very important
      to know the TNM stage of the tumour. The evaluation of N stage it is very
      difficult both preoperatively and intra-operatively and for this reason it
      becomes important the accurate staging of T. Recently the ultrasonography on the
      resected specimen allow us to correctly diagnose the depth of tumour invasion in
      more than 90% of the cases. Since there is a close correlation between the depth
      of tumour invasion and the incidence of node metastases, it is possible to
      identify to the most appropriate operation for each patient according to site and
      T of the tumour.

PMID- 9612646
TI  - Treatment of early gastric cancer.
AB  - Early or superficial gastric cancer identifies a lesion that is confined to the
      mucosa or submucosa layer and that even in the presence of lymph nodes metastasis
      can be successfully treated with resection and lymph node dissection. In presence
      of cancer that invades the submucosa the incidence of N2 metastasis raises to 3
      5%, and even though a D2 procedure is indicated as the postoperative mortality is
      similar to D1 procedure. Early gastric cancer of the mid portion of the stomach
      can be treated with a distal D2 pylorus preserving gastrectomy that has the
      advantage to reduce the incidence of dumping syndrome; this result can be
      achieved with a complete dissection of the infrapyloric nodes preservng part of
      the suprapyloric nodes to spare the right gastric artery. Endoscopic mucosal
      resection is another therapeutic option available in presence of a mucosal
      gastric cancer less than 2 cm, well differentiated without ulceration; among 50
      cases treated so far, 32 cases were completed resected and they are free of
      disease up to now. The main risks of this procedure are hemorrhage (5%) and
      perforation (6.4%).

PMID- 9612647
TI  - [Surgical treatment of stomach cancer: analysis of our personal experience].
AB  - The "curative" treatment of gastric carcinoma includes the complete removal of
      the tumour and of the nodes involved without any macroscopic residual of disease
      (RO). Out of 326 patients with gastric cancer observed, a series of 114
      consecutive patients underwent surgical resection (total gastrectomy or subtotal
      distal gastrectomy) with D2 or D3 lymphadenectomy. Overall operative mortality
      was 5.3%. Since 1988 no postoperative death occurred. Overall morbidity was
      15.8%, specific morbidity 10.5%, reduced after 1988 to 6.6%. No significant
      differences in operative mortality and need of blood transfusions were recorded
      between D2 and D3 lymphadenectomy. Overall 5-year survival was 32%. Univariate
      and multivariate analysis showed that only T and N stages are significant
      prognostic factors, whereas tumour location, total or subtotal gastrectomy in
      antral cancers, extent of lymphadenectomy (D2 vs D3) and histology were not
      significantly related to survival. Since most studies have clearly shown that T
      and N stages are the most important prognostic factors in gastric cancer, the
      present aim should be to plan the extent of surgical resection according to the T
      and N stages characteristics of the neoplasm.

PMID- 9612648
TI  - [Surgical treatment of gastric carcinoma: lymphadenectomy].
AB  - The review of the literature shows the improvement of outcome of patients with
      gastric cancer after resection and extended lymphadenectomy. Lymphadenectomy
      D2/D3 was performed in 206 out of 639 patients with gastric cancer: 5-year
      survival was 66.3% versus 41.5% of the 121 patients that underwent D1 resection
      (p < 0.0001). Univariate and multivariate analyses show that proximal location of
      the cancer, advanced stage and lymphadenectomy limited to perigastric stations
      are negative prognostic factors. Although there are still different opinions
      regarding D2 or D3 lymphadenectomies for the operative risks, pancreatic
      resection (preferring pancreas sparing techniques) and splenectomy is subtotal
      gastrectomy for antral carcinoma, extended lymphadenectomy remains an important
      point to improve survival.

PMID- 9612649
TI  - [Outcome of surgical treatment of cancer of the stomach. Report of 330 cases].
AB  - The study concerned 330 cases of gastric adenocarcinoma operated from January
      1969 to June 1996. Clinical, histological and therapeutic features were analyzed
      and compared during 3 periods (Group 1: 1969-79, Group 2: 1979-88, Group 3: 1989
      96). The aim was to evaluate changes and results occurred in gastric carcinoma.
      The median age was 65 +/- 11 year (range 25-90), the sex ratio 2. The most common
      location was in the lower third of the stomach and the cancer was often far
      advanced (71 percent of stages III and IV). Subtotal gastrectomy was replaced by
      total gastrectomy and large lymph node dissection was systematically performed in
      group 3. Curative resection rate increased from 28 to 60 percent between group 1
      and group 3. Despite the more radical surgery, post-operative mortality rates
      decreased respectively 22%, 9%, 8% for the groups 1, 2, 3 (p < 0.01) and global
      morbidity remained stable while the rate of intra-abdominal infection have
      changed in group 3 (4.8% vs 2.7% and 2.1% in respectively groups 1 and 2; p =
      ns). Two year survival rates were 20% for group 1.25% for group 2 and 35% for
      group 3 (p < 0.01). This results can be considered as encouraging but have to be
      confirmed at 5 year survival.

PMID- 9612650
TI  - [Complementary treatment to surgery of gastric carcinoma: role of adjuvant and
      neoadjuvant chemotherapy].
AB  - Although there has been a decline in the incidence of gastric cancer worldwide,
      its mortality rate is still high. In the West, attempts with adjuvant
      chemotherapy to improve survival have been disappointing. The promising results
      reported with the FAM (5-FU, Adriamycin, Mitomycin C) regimen in patients with
      advanced disease, have not been confirmed in an adjuvant setting. Randomized
      trials on adjuvant chemotherapy in Japan have shown a positive outcome in treated
      patients only when subgroups with advanced disease are considered. As results
      with adjuvant chemo-immunotherapy were better than those with chemotherapy alone,
      immunostimulators have been widely utilized in clinical trials conducted in Japan
      in recent years. However, chemo-immunotherapy may be more effective in patients
      with minimal residual disease, due to the combined action of a lower stage at
      diagnosis and to a diffuse application of standard wide lymphadenectomy.
      Inadequate lymphadenectomy, like that performed in many western studies, may
      compromised radicality in patients with "curable" disease and the concept of
      "minimal residual disease" must therefore be considered in future trials on
      adjuvant chemotherapy. Future trends for new therapeutic combinations (FAMTX,
      EAP, 5-FU/Cisplatin, PELF, etc) tested in phase II and III clinical trials are
      also discussed. Whatever the type of approach used, the high incidence of intra
      abdominal recurrences indicates that an improvement in the prognosis of patients
      with advanced diseases will only come with the development of additional
      treatment modalities such as neoadjuvant or intraperitoneal chemotherapy.

PMID- 9612651
TI  - ["Hepatoid" gastric tumor].
AB  - In this study the Authors describe two cases of hepatoid adenocarcinoma of the
      stomach: one is characterized by the presence of alpha-fetoprotein (AFP) high
      levels of the serum both pre and post-operating and by the very positive response
      to the adjuvant chemotherapy (how the return to the normality of such values
      demonstrates). The other is instead characterized by the presence of post
      operating hepatic metastasis, event which is very frequent in this kind of
      neoplasm, but presents many problems concerning the differential histological
      diagnostics with the primitive hepatocarcinoma (problems which are nowadays not
      completely solved). Moreover the Authors relate to this study the revision of the
      international literature of the main characteristics and of prognosis of this
      particular and rare neoplasm.

PMID- 9612652
TI  - [Prognostic value of histologic classifications of advanced stomach cancer:
      comparative study of Lauren's and Goseki's classifications].
AB  - Controversy exists about the prognostic value of the histological classifications
      of gastric cancer commonly used. Recently Goseki proposed a new classifying
      system based on intracellular mucus production and the degree of tubular
      differentiation. The aim of this study was to compare Lauren and Goseki
      classifications with particular emphasis on their prognostic significance. Eighty
      nine patients, who underwent potentially curative resections (RO) and radical
      lymphadenectomy for advanced gastric cancer from September 1988 to April 1996
      were analysed. Cox regression model was used to evaluate the prognostic
      significance of Goseki classification, Lauren classification, age, sex, type of
      lymphadenectomy, depth of tumour invasion (T), node metastases (N) and number of
      metastatic nodes. A statistically significant correlation between the different
      Goseki grades and histology according to Lauren was found (p < 0.001). By
      multivariate analysis the only parameters predictive of long term outcome were
      depth of tumour invasion, nodal status and histology according to the Lauren
      classification. Also after excluding the Lauren classification from the analysis,
      the Goseki histological grading system did not affect survival independently.
      This study on advanced gastric cancer patients identified depth of invasion,
      lymph node metastases and Lauren classification as significant independent
      pathological variables influencing survival. The classification proposed by
      Goseki did not add anything further to the prognostic informations provided by
      TNM staging and Lauren classification.

PMID- 9612653
TI  - [Multidisciplinary treatment of hepatocarcinoma].
AB  - Radical treatment of the hepatocellular carcinoma (HCC) is complete surgical
      removal; it may be done by resection or total hepatectomy. Although multicentric
      carcinogenesis predicts that liver transplantation is likely adequate to treat
      both the hepatoma and the underlying cirrhosis, it doesn't seem justified in the
      advanced stages or in absence of end-stage liver disease and therefore liver
      resection remains the treatment of choice for radical cure of HCC. However, low
      resectability and high recurrence rate make surgery alone ineffective.
      Unresectable HCC may be converted to resectable by multimodality
      radiation/chemotherapy, and embolization of portal branch feeding tumour,
      improving the function of the nonembolized liver, can extend the surgical
      indications for HCC. Adjuvant chemoembolization has already shown to reduce
      recurrence rate after radical resection and it should be widely applied. In
      unresectable or not converted HCCs as well as in postoperative recurrence,
      alternative therapies, particularly as multimodality treatment, can improve
      survival rate. To date, multidisciplinary treatment of hepatocellular carcinoma,
      waiting for further studies on newer modalities (prevention and gene therapy,
      especially), represents the best way to improve long-term results.

PMID- 9612654
TI  - [Treatment of Hirschsprung's disease with the Soave-Coran technique: experience
      with newborns and children].
AB  - Authors report their experience with Soave endorectal pull-through (ERPT)
      procedure modified by Coran for Hirschsprung's disease. At the Santobono
      Children's Hospital of Naples 30 patients have been operated for Hirschsprung's
      disease; 21 of them (age 10 days-3 years and 7 months) have undergone a Coran's
      procedure: a single stage procedure was performed in 16, the other 5 underwent
      ERPT following colostomy. Four complications occurred: 2 intestinal obstruction
      and 2 anastomotic leaks. Excellent long-term results reported from literature and
      proved by Author's experience suggest that one stage Coran's procedure can be
      safely performed even in neonates avoiding colostomy complications and reducing
      total duration and costs of hospitalization.

PMID- 9612655
TI  - Electrophysiological properties of the fibrillating atrium: implications for
      therapy.
AB  - 1. Atrial fibrillation (AF) is the most commonly occurring cardiac dysrhythmia
      and remains a challenge to medical therapy. Although the disorder has been
      recognized for over 100 years, surprisingly very little is understood about its
      pathophysiology. Over the past decade, a variety of experimental and animal
      models of AF have been developed and these have provided insights into the
      mechanism of AF. 2. The pathophysiology of AF is complex. Atrial fibrillation can
      be caused either by a single source of very rapid impulses or, in the majority of
      cases, by multiple random re-entering wavelets. The notion that AF may be
      initiated by a single rapid firing focus and the perpetuation of AF may be partly
      dependent on macro re-entry around the natural atrial orifices provides a new
      potential curative therapy for AF by radiofrequency ablation. 3. Shortening of
      atrial wavelength, either by slow atrial conduction velocities, short atrial
      refractory periods or both, seems to predispose to development of intra-atrial re
      entry and, thus, AF. The functional mechanism by which anti-arrhythmic drugs
      terminate AF appears to be by prolonging the wavelength and decreasing the number
      of re-entry wavelets. These understandings are important for the future
      development of effective anti-arrhythmic agents against AF. 4. The presence of a
      short and variable excitable gap during AF may be potentially important for
      termination of AF by pacing. 5. New insights are being gained into the potential
      role and mechanism of electrical remodelling of the atrium due to AF. Repeated
      induction of AF by rapid atrial pacing leads to a shortening of atrial
      refractoriness with loss of rate adaptation, which favours the induction and
      maintenance of AF. These electrophysiological changes were assumed to occur
      during repeated AF and to facilitate the generation of multiple re-entrant
      wavelets. These data suggest that prompt restoration of sinus rhythm and new
      novel therapy that prevents or diminishes electrical remodelling may promote
      maintenance of sinus rhythm after successful cardioversion.

PMID- 9612656
TI  - The consequences of deafness and chronic intracochlear electrical stimulation on
      the central auditory pathways.
AB  - 1. Auditory deprivation can result in significant morphological and physiological
      changes within the central auditory nervous system. These changes are generally
      more pronounced when the onset of deafness occurs early in development, as is the
      case with congenitally deaf children. 2. A review of the auditory plasticity
      literature suggests that some of these deafness-induced changes may be
      preventable or partially reversible by electrical stimulation of the auditory
      nerve. 3. With the increasing application of cochlear implants in congenitally
      deaf children, it is important to evaluate the consequences of introducing
      electrical stimulation to the developing auditory nervous system.

PMID- 9612657
TI  - Electrical basis of peristalsis in the mammalian upper urinary tract.
AB  - 1. Peristalsis in the mammalian upper urinary tract (UUT) is mostly myogenic in
      origin, originating predominately in the proximal pelvicalyceal regions of the
      renal pelvis, an area that is enriched with specialized smooth muscle cells
      termed 'atypical' smooth muscle cells. Propagating peristaltic contractions are
      little affected by blockers of either autonomic nerve function or nerve impulse
      propagation; however, blockers of sensory nerve function or prostaglandin
      synthesis reduce both the frequency and the strength of the spontaneous
      contractions underlying peristalsis. 2. The electrical drive for these
      peristaltic contractions has long been considered to involve mechanisms analogous
      to the heart, such that 'atypical' smooth muscle cells generate spontaneous
      'pacemaker' action potentials. These pacemaker potentials trigger the firing of
      action potentials and contraction in the muscular regions of the renal pelvis,
      which propagate distally to the ureter, propelling urine towards the bladder. 3.
      Recent intracellular microelectrode and single cell/channel patch-clamp studies
      have revealed that the ionic conductances underlying the action potentials
      recorded in the UUT are likely to involve the opening and slow closure of voltage
      activated 'L-type' Ca2+ channels, offset by the time-dependent opening and
      closure of both voltage- and Ca(2+)-activated K+ channels. 4. In the present
      review we summarize the current knowledge of the ionic mechanisms underlying
      action potential discharge in the UUT, as well as present our view on how this
      electrical activity supports the initiation and conduction of UUT peristalsis.

PMID- 9612658
TI  - Respiratory sinus dysrhythmia persists in transplanted human hearts following
      autonomic blockade.
AB  - 1. The present study was performed to test whether beat-to-beat cardiovascular
      control in cardiac allograft recipients resides in cholinergic and/or adrenergic
      nerves that are intrinsic to the heart. 2. Heart rate (HR) fluctuations
      synchronous with respiration during spontaneous, double tidal volume and
      metronome-synchronized breathing were quantified in 13 human heart transplant
      recipients. We also examined the effects of sequential cholinergic and beta
      adrenoceptor (combined) autonomic blockade on respiratory sinus arrhythmia (RSA).
      We computed RSA amplitude and the correlation between respiration and changes in
      HR (cardiopulmonary synchronization; CPS). Group means were compared using
      repeated-measures analysis of variance. Transplant recipients served as their own
      controls. 3. In the basal state, moderate RSA amplitude and CPS were observed.
      During cholinergic and combined blockade, we observed no significant change in
      RSA amplitude, whereas CPS increased significantly during combined blockade (P <
      0.05). The amplitude of RSA increased during respiration at double baseline tidal
      volume, but not at any of the other breathing manoeuvres (P < 0.01). In contrast,
      CPS increased significantly during both patterned breathing manoeuvres. No
      significant correlation was seen between mean right atrial pressure and RSA
      amplitude. In 23% of subjects with low CPS, HR oscillated with arterial pressure.
      These oscillations were independent of respiration. During all three patterns of
      respiration, a significant inverse correlation was observed between CPS and pulse
      pressure (r = -0.53 to -0.73). Thus, as the amplitude of pulse pressure
      increased, respiration accounted for a smaller percentage of HR variation. 4. In
      conclusion, RSA persists and the magnitude of CPS increases following combined
      autonomic blockade. These studies suggest that while RSA after cardiac
      transplantation is not cholinergically or adrenergically mediated, it may be
      related to mechanical stretch of the sinus node caused by changes in
      intrathoracic pressure and perfusion pressure.

PMID- 9612659
TI  - Modulation of electrically evoked responses in rat duodenum by activation of
      nicotinic cholinoceptors.
AB  - 1. The effect of activation of nicotinic cholinoceptors in rat duodenal segments
      following electrical field stimulation (EFS) was investigated. 2. Electrical
      field stimulation elicited a two-component response: transient relaxation
      followed by contraction. The EFS-evoked response was tetrodotoxin (TTX; 1
      mumol/L) sensitive. The relaxation component was NG-nitro-L-arginine (L-NNA; 100
      mumol/L) sensitive, while the contractile response was atropine (1 mumol/L)
      sensitive. 3. 1,1-Dimethyl-4-phenyl-piperazinium iodide (DMPP; 20 mumol/L)
      induced relaxation of spontaneously active preparations that was L-NNA sensitive.
      L-Arginine (1 mmol/L) reversed the effects of L-NNA on DMPP-induced relaxation.
      4. When EFS was applied, DMPP increased the amplitude of the relaxation component
      of the response and reduced the contractile component. 5. In the presence of L
      NNA, the effect of DMPP on the relaxation component of the response to EFS was
      reduced, but the contractile response was not affected. L-Arginine partly reduced
      this effect of L-NNA. 6. Neither propranolol (1 mumol/L) nor yohimbine (1
      mumol/L) had any effect on the actions of DMPP on EFS-evoked responses, but
      prazosin (1 mumol/L) strongly reduced the effect of DMPP on the contractile
      component of the response to EFS and slightly reduced the effect of DMPP on the
      relaxation response. 7. Histochemical studies demonstrated that, in the myenteric
      plexus of the rat duodenum, there are many reduced nicotinamide adenine
      dinucleotide phosphate-diaphorase (NADPH-d)-positive neurons and that their
      number decreased after treatment with L-NNA. In the presence of L-arginine and L
      NNA, the number of NADPH-d-positive neurons was similar to that found in control
      samples. 8. The data suggest that activation of nicotinic cholinoceptors
      modulates EFS-evoked responses in the rat duodenum as a result of the
      potentiation of nitrergic and adrenergic neurotransmission.

PMID- 9612660
TI  - Propofol block of cardiac sodium currents in rat isolated myocardial cells is
      increased at depolarized resting potentials.
AB  - 1. The effect of propofol on cardiac whole-cell sodium currents and single sodium
      channels in rat isolated ventricular myocytes was examined using patch-clamp
      techniques. 2. Propofol caused a block of the whole-cell sodium current, the
      potency of block depending on the holding potential. When cells were held at -90
      mV, the EC50 was 2.8 micrograms/mL. When cells were held more hyperpolarized (at 
      140 mV), the EC50 increased to 44.0 micrograms/mL. 3. Although the degree of
      block produced by the same concentration of propofol was different at different
      holding potentials, the time course of onset and recovery from block was the
      same. 4. The current/voltage relationship for the sodium current showed a
      pronounced block of peak current by propofol (40-50% block of the maximum current
      by 30 micrograms/mL propofol), with a minimal shift in the voltage dependence of
      activation and no shift in reversal potential. 5. The voltage dependence of the
      steady state inactivation curve was shifted to more hyperpolarized potentials by
      propofol (shift of 18 and 8 mV by 30 and 10 micrograms/mL propofol,
      respectively). 6. Single channel records showed that propofol caused a shortening
      of the mean channel open time (from a mean of 0.59 to 0.38 ms by 10 micrograms/mL
      propofol), but no change in the channel amplitude. 7. It is concluded that
      propofol produces a block of sodium currents in cardiac myocytes at
      concentrations that are comparable to those that may be attained during
      anaesthesia.

PMID- 9612661
TI  - Blunted natriuretic response to endogenous atrial natriuretic peptide during
      rapid cardiac pacing in anaesthetized dogs.
AB  - 1. We investigated whether diuresis and natriuresis induced by endogenous atrial
      natriuretic peptide (ANP) were blunted during rapid cardiac pacing. 2. Changes in
      plasma ANP, renal function and haemodynamics during rapid cardiac pacing were
      studied in anaesthetized closed-chest dogs. Dogs were paced via the right
      ventricle at a rate of 200 b.p.m. (moderate pacing) or 250 b.p.m. (severe pacing)
      for 180 min. 3. The maximal increases in plasma ANP and urinary excretion of cGMP
      during severe pacing were four- and three-fold higher, respectively, than those
      during moderate pacing. Despite the higher concentration of plasma ANP, the
      maximal increases in urine volume, urinary excretion of sodium and fractional
      excretion of sodium during severe pacing were similar to those during moderate
      pacing. Mean arterial pressure and renal vascular resistance were decreased only
      by severe pacing. The increase in total peripheral resistance during severe
      pacing was significantly smaller than that during moderate pacing. However, the
      glomerular filtration rate was kept at basal levels by both moderate and severe
      pacing. 4. These results suggest that there are certain mechanisms that
      counteract renal tubular sodium reabsorption induced by endogenous ANP under
      conditions of severe pacing. The suppression occurs at tubular sites but at
      glomerular sites. One of the possibilities for the suppression is the decrease in
      renal perfusion pressure accompanied by decreases in peritubular capillary
      hydrostatic pressure.

PMID- 9612662
TI  - Calcium channel blocking and vasodilating actions of the novel dihydropyridine
      derivative AE0047.
AB  - 1. The pharmacological characteristics of AE0047, a newly synthesized
      dihydropyridine (DHP) derivative, were investigated in vitro. 2. In bovine aortic
      membrane, AE0047 and other DHP calcium channel blockers (nitrendipine,
      nicardipine) displayed concentration-dependent antagonism to specific [3H]-PN200
      110 binding sites with the following values for inhibition constants (Ki)
      obtained: 20.8 +/- 8.9, 12.3 +/- 4.5 and 3.9 +/- 1.0 nmol/L for AE0047,
      nitrendipine and nicardipine, respectively. 3. In guinea-pig ventricular
      myocytes, AE0047 blocked the L-type calcium current, with values for the
      dissociation constant (Kd) and Hill coefficient of 11.4 +/- 5.7 nmol/L and 0.852
      +/- 0.061, respectively, indicating in the terms of Hill's hypothesis that one
      drug molecule blocks one calcium channel molecule. 4. In rat aorta, AE0047
      inhibited 45Ca uptake induced by high K+ (100 mmol/L) by 55%. 5. AE0047 and
      nitrendipine concentration dependently relaxed rat aortic strips contracted with
      30 mmol/L KCl. The response to nitrendipine reached a plateau within 60 min and
      disappeared after drug washing. Interestingly, AE0047 required 5 h or more to
      produce a plateau of response, with no effect of drug washing. This confirmed the
      slow onset and long duration of its vasodilating action. 6. With AE0047, tissue
      content in rat aorta increased more slowly than with nitrendipine and release of
      AE0047 from tissue was also slower. 7. The data suggest that AE0047 is
      incorporated slowly into smooth muscle membranes, approaches receptors slowly
      through the membrane bilayer and accumulates in the membrane because of its high
      lipophilicity, resulting in an anti-hypertensive action that is slow in onset and
      of long duration.

PMID- 9612663
TI  - Vasorelaxant effects of SCA40 (a phosphodiesterase III inhibitor) in pulmonary
      vascular preparations in rats.
AB  - 1. The novel phosphodiesterase (PDE) inhibitor SCA40 (6-bromo
      8(methylamino)imidazo[1,2-a]pyrazine-2-carbonitrile) was examined for its
      vasorelaxant activity on isolated pulmonary vascular preparations from rats. 2.
      SCA40 relaxed ring preparations of main and intralobar pulmonary artery
      precontracted submaximally with either phenylephrine or U46619 (thromboxane
      mimetic). Based on negative log EC50 values, SCA40 was six-to 14-fold more potent
      than the PDE III inhibitor milrinone or the non-selective PDE inhibitor 3
      isobutyl-1-methyl xanthine (IBMX). The potency of SCA40 corresponded to its
      reported potency as a PDE III inhibitor. 3. In isolated perfused lungs, SCA40
      reversed the vasoconstriction induced by alveolar hypoxia. It was 49-fold more
      potent than IBMX. 4. In main pulmonary artery the vasorelaxation induced by SCA40
      was not blocked by the large-conductance calcium-activated potassium channel
      (BKCa) inhibitors iberiotoxin (50 and 100 nmol/L) or charybdotoxin (100 and 300
      nmol/L). This was in contrast to data on guinea-pig trachea, where responses to
      SCA40 were significantly inhibited by charybdotoxin (100 nmol/L). 5. It is
      concluded that opening of BKCa channels does not contribute to the pulmonary
      vasorelaxant effects of SCA40 in main pulmonary artery and it is likely that
      responses reflect the PDE III inhibitory properties of the drug. 6. It is
      postulated that SCA40 may be useful as a pulmonary vasodilator in disorders such
      as pulmonary hypertension.

PMID- 9612664
TI  - Permeability of the developing and mature blood-brain barriers to theophylline in
      rats.
AB  - 1. In the present study, the uptake of theophylline and L-glucose into the adult
      and neonatal rat brain has been investigated. Steady state cerebrospinal fluid
      (CSF) and brain concentrations of theophylline were reached within 1 h following
      a single intraperitoneal (i.p.) injection, whereas steady state CSF and brain
      concentrations of L-glucose were not approached until after 5 h. 2. Steady state
      brain:plasma and CSF:plasma concentration ratios for theophylline and L-glucose
      in neonatal rats were significantly higher than ratios in adult rats.
      Erythrocyte:plasma ratios for theophylline in neonatal rats were also
      significantly higher than ratios in adult rats. Steady state ratios for
      theophylline were significantly higher than those for L-glucose in both neonatal
      and adult rats. 3. Respiratory acidosis (pH 6.9-7.0) did not affect steady state
      CSF:plasma or brain:plasma ratios for theophylline in neonatal or adult rats. In
      contrast, steady state CSF:plasma and brain:plasma ratios for L-glucose were
      increased by respiratory acidosis. 4. The lower steady state CSF:plasma,
      brain:plasma and erythrocyte:plasma ratios for theophylline in adult rats are
      likely to be due to a higher concentration of plasma proteins in adult blood
      compared with neonates, with a greater retention of protein-bound (non
      exchangeable) theophylline in adult blood, and are unlikely to be due to p
      glycoprotein-mediated efflux of theophylline at the adult blood-brain barrier.

PMID- 9612666
TI  - Effect of grapefruit juice on urinary 6 beta-hydroxycortisol/cortisol excretion.
AB  - 1. The aim of the present study was to evaluate the effect of grapefruit juice on
      urinary 6 beta-hydroxycortisol and cortisol excretion in healthy subjects. 2. The
      ratio of 6 beta-hydroxycortisol/cortisol was significantly decreased (P = 0.036)
      in the 0-4 h fraction of urine after ingestion of grapefruit juice, but not in
      the 4-24 h fraction (P = 0.218) or for the compiled data, fraction 0-24 h (P =
      0.114). 3. These results indicate that endogenous cortisol metabolism may not
      only be of hepatic origin, but may also be dependent on the metabolic capacity of
      cytochrome P450 IIIA (CYP3A) in the gut mucosa. 4. This finding may cast further
      doubts of the usefulness of the 6 beta-hydroxycortisol/cortisol ratio as an
      indicator of hepatic CYP3A activity.

PMID- 9612667
TI  - Steroid therapy for chronic obstructive pulmonary disease.
AB  - Both inhaled and oral corticosteroids have proven benefit in the management of
      asthma, but their efficacy in nonasthmatic, smoking-related chronic obstructive
      pulmonary disease (COPD) remains controversial. Recent data suggest that
      responsiveness to beta 2-agonists predicts oral and inhaled steroid
      responsiveness in most patients with COPD, however, a poor bronchodilator
      response does not preclude a good response to steroids. COPD patients with
      histologic, cytologic, or biochemical indices of inflammation characteristic of
      asthma, such as sputum eosinophilia, are more likely to be steroid responsive
      than are COPD patients without these characteristics. Contrary to previous
      experience, steroid responsiveness does not appear to be an all-or-nothing
      phenomenon; rather there appears to be a continuous spectrum of steroid responses
      from none to marked. The effects of long-term inhaled steroid use on the natural
      progression of chronic airflow obstruction are currently under investigation.

PMID- 9612668
TI  - Noninvasive positive-pressure ventilation in chronic obstructive pulmonary
      disease.
AB  - Interest in noninvasive positive-pressure ventilation both as an alternative to
      intubation and mechanical ventilation and as a unique therapy has grown over
      recent years. Clinical and patient acceptance is highest in neuromuscular
      deficits, but supporting evidence for its use in chronic obstructive pulmonary
      disease is highly dependent on the application. This review considers the
      clinical implementation of noninvasive positive-pressure ventilation in acute
      respiratory failure, as a postextubation weaning alternative, in stable severe
      hypercapnic chronic obstructive pulmonary disease, in overlap syndrome, and for
      nocturnal oxygen desaturation. Some applications are well supported, leading to a
      cautious recommendation for its utilizatip4, whereas for others evidence is
      starkly conflicting. The clinical efficacy of noninvasive positive-pressure
      ventilation is vastly dependent on equipment, equipment-patient interface,
      pressure settings, physician's bedside manner, and experience of the center.
      Interpretation of the studies must take into account the foregoing factors along
      with the various ventilatory techniques and differing primary outcome measures.
      Generalizations can be made regarding indications and contraindications, but this
      is an area rife with exceptions. The subtle message from the clinical studies
      describes the importance of the clinical art applied from the palette of science
      and technology.

PMID- 9612665
TI  - Hypothesis: aldosterone is synthesized by an alternative pathway during severe
      sodium depletion. 'A new wine in an old bottle'.
AB  - 1. The last three steps of aldosterone biosynthesis, 11 beta-hydroxylation, 18
      hydroxylation and 18-oxidation, have been demonstrated to be catalysed by one
      enzyme, which is the cytochrome P450(11 beta) (CYP11B) in cow, pig, sheep and
      bullfrog or cytochrome P450aldo (CYP11B2) in rat, human, mouse and hamster. 2.
      The related enzyme P450(11 beta) (CYP11B1) from rat, human, mouse and hamster
      adrenals displays 11 beta-hydroxylation and 18-hydroxylation activities, but not
      18-oxidation activity in vitro. No such enzyme has been reported in the cow, pig
      or sheep to date. 3. Data showing the dissociation of aldosterone secretion from
      plasma angiotensin II (AngII) levels indicate the presence of other factor(s)
      that regulate aldosterone biosynthesis in response to changes in body sodium
      status. Thus, we propose the existence of a 'sodium status factor' that regulates
      aldosterone biosynthesis in addition to AngII, K+, adrenocorticotropic hormone
      and atrial natriuretic peptide. 4. We propose that during severe sodium
      deficiency there is a switch in the aldosterone pathway to a pathway using 18
      hydroxy-deoxycorticosterone (18-OH-DOC) rather than corticosterone as an
      intermediate. This switch may be mediated via the putative 'sodium status
      factor'. 5. Two models of the hypothesis will be discussed in this paper: (i) a
      'one-enzyme' model; and (ii) a 'two-enzyme' model. 6. The one-enzyme model
      proposes that P450aldo (P450(11 beta) as in the case of the cow, sheep and pig)
      changes its enzymatic activity during severe sodium deficiency (i.e. switching to
      the alternative aldosterone biosynthesis pathway). 7. The two-enzyme model
      proposes that, under normal circumstances, P450aldo synthesizes aldosterone from
      deoxycorticosterone, while during severe sodium deficiency the P450(11 beta)
      provides the substrate (i.e. 18-OH-DOC) for the P450aldo.

PMID- 9612669
TI  - Chronic obstructive pulmonary disease international guidelines.
AB  - Although chronic obstructive pulmonary disease (COPD) has a public health
      importance similar to asthma, it has received less attention. The first guideline
      on the management of COPD was released in 1987 by the American Thoracic Society.
      In 1992 the Canadian Thoracic Society released its guidelines. In 1995 the
      European Respiratory Society and the Thoracic Society of Australia and New
      Zealand released their guidelines and the American Thoracic Society updated and
      expand its COPD guidelines. All these documents were followed in 1997 by the
      guidelines developed by the British Thoracic Society. These COPD guidelines show
      many similarities but also have some interesting differences. The aim of this
      paper is to review these similarities and discrepancies. Like all guidelines,
      COPD guidelines suffer from the limited amount of evidence-based medicine
      supporting them, a limitation that, however, provides a strong stimulus for
      further research.

PMID- 9612670
TI  - Computed tomographic imaging of bronchiolar disorders.
AB  - The bronchiolitides can be categorized broadly as constrictive or proliferative,
      each with characteristic CT features. The cardinal CT signs of constrictive
      bronchiolitis are mosaic perfusion, enhanced on expiratory CT scan and variably
      associated with bronchiectasis and, less frequently, centrilobular branching
      structures. These features are common to postinfective bronchiolitis,
      bronchiolitis associated with collagen vascular disease, obliterative
      bronchiolitis following lung transplantation, and bronchiolitis following
      inhalation of toxic fumes and consumption of Sauropus androgynus. Proliferative
      bronchiolitis manifests on CT scan as patchy bilateral consolidation, variably
      associated with nodular abnormalities. The CT appearances of other rare
      bronchiolitides are discussed here including diffuse panbronchiolitis, follicular
      bronchiolitis, and respiratory bronchiolitis-associated interstitial lung
      disease.

PMID- 9612671
TI  - Heterogeneity of bronchiolitis obliterans organizing pneumonia.
AB  - Reports of the characterization and understanding of bronchiolitis obliterans
      organizing pneumonia (BOOP) have continued at an accelerated rate for several
      years. The radiographic and high-resolution CT features of BOOP continue to be
      documented. There have been new insights into the pathogenesis of BOOP. An animal
      model has been developed. Video-assisted thoracoscopic biopsy has become a
      standard for confirming the diagnosis. Childhood BOOP has been described in
      several reports. Idiopathic BOOP continues to be the most common type; however, a
      variety of clinical settings such as inhalation of mold spores and associated
      disorders such as renal transplantation continue to be described. This paper
      provides an update of advances in the pathogenesis, radiographic features,
      clinical course, and categorization of the heterogeneity of BOOP.

PMID- 9612672
TI  - Chronic bronchioloalveolitis associated with human T-cell lymphotrophic virus
      type I infection.
AB  - The lung is a preferential site for human T-cell lymphotropic virus type I
      infection. This peculiar tropism for the lung is responsible for the high
      incidence of pulmonary involvement in patients with human T-cell lymphotropic
      virus type I infection. A variety of pulmonary manifestations may be present in
      human T-cell lymphotropic virus type I-associated pulmonary diseases, but the
      characteristic features of this disorder appear to be chronic
      bronchioloalveolitis with or without fibrotic changes of surrounding parenchyma.
      As for the pathogenesis of pulmonary involvement associated with human T-cell
      lymphotropic virus type I infection, immunologic mechanisms through T-cell
      activation may play an important role. Such attractive interpretations need
      further verification.

PMID- 9612673
TI  - New developments in approaches to smoking cessation.
AB  - Tobacco use is the leading cause of unnecessary illness and death in the United
      States consuming billions of dollars in scarce health care resources. In the
      period under review, several new treatments for tobacco addiction were
      introduced. New nicotine delivery systems, a nasal spray and an inhaler, reduced
      craving and withdrawal compared with placebo and improved medium- to long-term
      cessation rates. Nicotine patches and gum became available without a prescription
      in the United States, offering the potential for increased use and synergy
      between public health efforts and commercial advertising. Important new safety
      data were obtained on the use of nicotine replacement therapies in potentially
      high risk groups, such as adolescents, pregnant women, and persons with serious
      cardiovascular disease, indicating that these therapies pose little or no
      additional risk.

PMID- 9612674
TI  - Health-related quality of life in patients with chronic obstructive pulmonary
      disease.
AB  - Health-related quality of life is usually impaired in patients with moderate to
      severe chronic obstructive pulmonary disease. The Sickness Impact Profile, the
      Medical Outcome Study "short form" 36, and the Nottingham Health Profile have all
      been used as generic measures of health-related quality of life. Although the
      discriminative properties of three disease-specific instruments, the Chronic
      Respiratory Disease Questionnaire, the St. George's Respiratory Questionnaire,
      and the Breathing Problems Questionnaire, are similar, the responsiveness of the
      Chronic Respiratory Disease Questionnaire and the St. George's Respiratory
      Questionnaire has been the most clearly demonstrated. The characteristics of each
      instrument should be considered in the selection of specific health-related
      quality of life questionnaires for clinical research.

PMID- 9612675
TI  - Erythromycin treatment in diffuse panbronchiolitis.
AB  - Diffuse panbronchiolitis is a chronic infectious airway disease that mainly
      occurs in the Far East. The prognosis for diffuse panbronchiolitis has
      dramatically improved over the past 10 years with the use of low-dose long-term
      erythromycin treatment. The beneficial effect of erythromycin and other 14
      membered-ring macrolides in this condition is considered to be due to an anti
      inflammatory rather than anti-infective mechanism. Recent investigations have
      revealed many new actions to the airway epithelial and inflammatory cells, e.g.,
      neutrophils, lymphocytes, and macrophages. Furthermore, erythromycin treatment of
      diffuse panbronchiolitis provides a new understanding of the pathophysiology and
      the treatment of chronic infectious airway disease.

PMID- 9612676
TI  - Etiology and diagnosis of prostate cancer: what's new? A review.

PMID- 9612677
TI  - Transurethral electrovaporization of the prostate vs. transurethral resection.
      Results of a multicentric, randomized clinical study on 150 patients.
AB  - AIM OF THE STUDY: To evaluate clinical, urodynamic efficacy and safety of TURP
      and TVP in patients with symptoms due to obstructive benign prostatic hypertrophy
      with a prospective multicentric randomized study. MATERIALS AND METHODS: 150
      patients with BPH, urodynamically obstructed, were randomized to receive TURP or
      TVP. At the end of the recruitment phase, 80 patients underwent TURP and 70
      patients underwent TVP. Patients were clinically evaluated by the I-PSS score at
      months 0, 1, 3, 6 and 12. Preoperative evaluation included complete blood routine
      examination, PSA, transrectal ultrasound and pressure/flow studies. Pressure/flow
      studies were also performed after 3 months. RESULTS: There was no statistical
      difference between groups in any of the preoperative parameters. All patients
      were considered urodynamically obstructed at preoperative pressure studies. As
      for catheter days and hospitalization days, statistical differences between TVP
      and TURP were found; catheter days were 2.71 days (SE 0.12) in the TURP group vs.
      1.9 (SE 0.24) in the TVP group (p < 0.000). Hospitalization was 4.7 days (SE
      0.22) after TURP and 3.9 days (SE 0.24) after TVP (p < 0.000). Mean preoperative
      I-PSS score was 18.84 and 18.19 in the TVP and TURP groups, respectively. At 3, 6
      and 12 months, IPSS was 5.52 and 5.50, 3.77 and 4.94, 3.52 and 4.04 for TURP and
      TVP, respectively. Mean preoperative peak flow rate (PFR) was 8.78 and 7.26 ml/s
      for TURP and TVP, respectively; after 3, 6 and 12 months, PFR was 19.21 and 18.8,
      20.77 and 20.13, 20.30 and 20.31 ml/s, respectively. After 3 months, 6 patients
      in the TURP group (7.5%) and 7 patients in the TVP group (10%) were borderline
      obstructed. 1 patient in the TVP group (1.4%) was still obstructed and underwent
      TURP. As for complications, 4 patients (5.7%) in the TVP group had stress urinary
      incontinence after 12 months vs. 1 (1.25%) in the TURP group. DISCUSSION: The
      present study clearly demonstrates that TVP is as effective as TURP in relieving
      urinary obstruction due to BPH, it offers some advantages in terms of
      catheterization and hospital stay, but at the price of a higher incidence of
      postoperative urine incontinence. Technical improvements might solve this problem
      in the future, perhaps combining TVP with TURP of the apical tissue.

PMID- 9612678
TI  - Infection after transurethral resection of the prostate: variation among centers
      and correlation with a long-lasting surgical procedure. Association pour la
      Recherche en Anesthesie-Reanimation.
AB  - OBJECTIVES: The purpose of this study was to analyze the risk factors of
      postoperative infection following transurethral resection of the prostate (TURP).
      METHODS: 857 consecutive patients scheduled for TURP were included in a French
      multicenter prospective study (12 surgical centers). For each patient, data were
      collected and analyzed as risk factors of postoperative infection. Statistical
      analysis used the chi 2 test or Student's test for univariate analysis, then
      stepwise logistic regression for multivariate analysis. RESULTS: The incidence of
      post-TURP infection was 21.6%: urinary tract infection (19.3%) and bacteremia
      and/or septic shock (2.3%). Multivariate analysis documented three independent
      risk factors of postoperative infection: preoperative bacteriuria (p < 0.003),
      duration of surgical procedure > 70 min (p < 0.01) and the surgical center (p <
      0.00001). CONCLUSION: The duration of the surgical procedure is an important
      postoperative risk factor of infection and there is a major difference between
      centers in terms of postoperative risk of infection. Further studies are needed
      to explain this last phenomenon.

PMID- 9612679
TI  - Incontinence after surgery for benign prostatic hypertrophy: the case for complex
      approach and treatment.
AB  - OBJECTIVE: Whether incontinence after surgery for benign prostatic hypertrophy
      (BPH) requires simple workup and treatment or being a more complex condition and
      multifactorial in etiology requiring combined surgical techniques should be
      investigated in more detail. METHODS: We retrospectively reviewed the records of
      56 patients referred to us for post-prostatectomy incontinence after surgery for
      BPH. All patients were subjected to urodynamics. Twenty-three (41.1%) patients
      required additional ascending urethrogram and/or cystourethroscopy, according to
      their associated symptomatology and the urodynamic findings, for a definitive
      diagnosis to be established. RESULTS: Twenty-four patients (42.8%) were found to
      have complex incontinence (either mixed or any type associated with bladder
      outlet stenosis), requiring combined treatment. Twenty-three (41.1%) had a simple
      type of incontinence, i.e., pure sphincter incompetence or unstable detrusor.
      Three patients had residual adenoma and 1 urethral stricture, while 5 patients
      (8.9%) remained unclassified. Thirty-seven patients were subjected to treatment,
      27 (73%) of them to single-modality treatment (artificial urinary sphincter
      insertion, oxybutynin chloride, transurethral prostatectomy, optical urethrotomy)
      and the other 10 (27%) to combined treatment (artificial urinary sphincter
      insertion plus urethroplasty, ileocystoplasty, permanent urethral stent
      implantation etc.). The overall socially acceptable continence rate (cured plus
      significantly improved) of the patients subjected to artificial urinary sphincter
      insertion reached 85%, being better (90%) for the uncomplicated sphincter
      incompetence group. CONCLUSIONS: Incontinence after surgery for BPH represents a
      condition that requires careful evaluation. In a significant proportion of
      patients, a combination of prosthetic and reconstructive techniques is needed for
      an optimal result to be achieved.

PMID- 9612681
TI  - Anastomotic stricture after radical prostatectomy. Incidence, findings and
      treatment.
AB  - OBJECTIVES: Stricture of the vesico-urethral anastomosis is a well-known
      complication after radical prostatectomy. Dilatation, stricture incision or
      resection have been proposed for endoscopic treatment. METHODS: In a
      retrospective study of 340 patients with prostatic cancer who underwent a radical
      retropubic prostatectomy from 1988 until 1996, we looked at the incidence of
      anastomotic strictures. RESULTS: An anastomotic stricture was found in 24 cases
      (7%) requiring endoscopic treatment. Based on prospective X-ray studies, we were
      able to show that the site of stricture is located below the bladder neck
      musculature in most cases well above the distal urethral sphincter and pelvic
      floor. No continence problems were encountered following structure resection in a
      follow-up of 12-72 months determined by a questionnaire and pad test. CONCLUSION:
      The transurethral resection of anastomotic stricture allows for a rather generous
      tissue resection, which is preferable to incision or dilatation in our hands.

PMID- 9612680
TI  - Is prostate-specific antigen a reliable marker of bone metastasis in patients
      with newly diagnosed cancer of the prostate?
AB  - OBJECTIVE: Staging in patients with newly diagnosed cancer of the prostate has
      significant ramifications in the management of the disease. At present,
      measurement of serum prostate-specific antigen (PSA) concentration and
      radionuclide bone scintigraphy are two important procedures in the metastatic
      work-up of these patients. We evaluated the efficacy of PSA as a staging marker
      to discriminate prostate cancer patients with and without bone metastases.
      METHODS: In a retrospective study, 359 prostate cancer patients with (n = 40) and
      without (n = 319) bone metastases were analyzed. In all patients the initial PSA
      measurement as well as the radionuclide bone scan were evaluated. RESULTS:
      Patients without bone metastases demonstrated a median serum PSA concentration of
      12 ng/ml, whereas those with bone metastases revealed a median serum PSA
      concentration of 59 ng/ml, with 7 patients demonstrating a serum PSA
      concentration of < 10 ng/ml. This resulted in a negative predictive value of 96%.
      In addition, only 40% of these patients with bone metastases demonstrated a serum
      PSA concentration of > 100 ng/ml, which resulted in a positive predictive value
      of 50%. CONCLUSION: The serum PSA concentration seems only to provide limited
      information with regard to the presence of bone metastasis in patients with newly
      diagnosed cancer of the prostate. We therefore question whether a staging
      radionuclide bone scan may be omitted in patients with a serum PSA value of < 10
      ng/ml.

PMID- 9612682
TI  - Urinary NMP22 and karyometry in the diagnosis and follow-up of patients with
      superficial bladder cancer.
AB  - OBJECTIVE: To study the value of two outpatient urine tests with regard to the
      diagnosis and recurrence of bladder tumors. METHODS: Fifty patients with a
      history of superficial bladder cancer were evaluated with urinary NMP22 levels
      (cutoff level 10 U/ml), bladder wash karyometry (low versus intermediate and high
      risk) and cystoscopy. All patients were followed for 1 year. RESULTS: Diagnostic
      negative and positive predictive values (NPV and PPV) of the tests were,
      respectively: NMP22 91.2 and 56.3%, and karyometry 80 and 33.3%. Prognostic NPV
      and PPV with regard to a subsequent recurrence were, respectively: NMP22 77.8 and
      27.3%, and karyometry 82.6 and 50%. CONCLUSION: The diagnostic value of NMP22 is
      good. Since the 3 false-negative results were in low-stage and low-grade lesions,
      this test could be used as a prescreening for cystoscopy. The NPV of these tests
      with regard to tumor recurrence is around 80%, but only karyometry has a
      significant PPV. Change in the follow-up policy on the basis of these tests
      remains difficult. In patients with neobladders NMP22 appears to be of little
      use, because of the high urinary NMP22 levels in the absence of malignancy.

PMID- 9612683
TI  - High incidence of brain metastases in patients treated with an M-VAC regimen for
      advanced bladder cancer.
AB  - OBJECTIVE: We report on central nervous system metastases from urothelial bladder
      carcinoma in patients treated with M-VAC chemotherapy. METHODS: 50 patients with
      advanced transitional cell carcinoma of the bladder were treated with the M-VAC
      regimen at the Hopital Cochin (Paris, France) between December 1989 and February
      1995. Brain relapses were diagnosed by CT scanning. RESULTS: We observed a
      surprising increase in the number of central nervous system relapses (8/50) in
      patients treated consecutively at the same institution. The mean time to
      metastatic recurrence in the brain from the initiation of first chemotherapy was
      21 months (range 7-38). Six patients had single and 2 patients had multiple
      central nervous system metastases. Treatment consisted of radiotherapy alone (n =
      5) or both surgery and radiotherapy (n = 3). Median survival time from the
      appearance of cerebral metastases was 3 months (range 1-10). CONCLUSION: The
      prolonged duration of remissions which are achieved following M-VAC chemotherapy
      may explain the greater likelihood of the detection of cerebral involvement.

PMID- 9612684
TI  - Single stones of the lower pole of the kidney. Comparative results of
      extracorporeal shock wave lithotripsy and percutaneous nephrolithotomy.
AB  - OBJECTIVE: To assess the effectiveness of extracorporeal shock wave lithotripsy
      (ESWL) and percutaneous nephrolithotomy (PCN) as a treatment for stones of the
      lower pole of the kidney and to compare their morbidity according to the stone
      size. METHODS: We retrospectively studied 739 patients treated for a single stone
      of the lower pole. Group I consisted of 666 patients treated by ESWL and group II
      consisted of 73 patients treated by PCN. RESULTS: These were assessed at 3 months
      for 587 ESWL patients (88%) and at day 1 for all PCN patients on renal tomography
      or ultrasonography. Respectively in groups I and II, 335 patients (57%) and 53
      patients (72.6%) were stone-free (p = 0.01). For medium-size (10-20 mm) stone
      patients, stone-free represented 102 patients (44%) and 29 patients (72.5%) in
      groups I and II respectively (p = 0.001). For smaller stones (< 10 mm), stone
      free represented 231 patients (69%) and 21 patients (84%) in groups I and II
      respectively (p = 0.12). Morbidity rate was less with ESWL than with PCN.
      CONCLUSIONS: PCN achieves better results than ESWL for single stone of the lower
      pole with statistical significance for middle-size stones but with higher
      morbidity.

PMID- 9612685
TI  - Corporeal plication for surgical correction of penile curvature. Experience with
      60 patients.
AB  - OBJECTIVE: To evaluate the efficacy of tunica albuginea plication without
      excision in patients with congenital and acquired penile curvature. METHODS:
      Results were retrospectively analyzed in 60 consecutive patients treated from
      1982 to 1996. Mean age was 42.8 years (range 16-77). 25 patients had congenital
      curvature and 35 patients had acquired curvature (29 Peyronie's disease, 5
      postoperative and 1 posttrauma). All patients had penile curvature with
      angulation over 30 degrees and major intercourse difficulties. RESULTS:
      Postoperatively, 52 patients (87%) had satisfactory cosmetic results and 49 (82%)
      had satisfactory functional results. All patients (100%) with congenital or
      postoperative curvature had satisfactory cosmetic results and satisfactory
      functional results. Patients with Peyronie's disease had a lower success rate
      with 81% satisfactory cosmetic results and 62% satisfactory functional results.
      CONCLUSION: Tunica albuginea plication is a more simple procedure than tunica
      albuginea resection (Nesbit procedure) with a comparable success rate and minimal
      morbidity.

PMID- 9612686
TI  - Selective use of cutaneous vesicostomy in prenatally detected and clinically
      presenting uropathies.
AB  - OBJECTIVES: To determine if the indications for cutaneous vesicostomy have
      changed with the advent of prenatal diagnosis and to assess if temporary
      vesicostomy remains an effective measure in preventing urinary infection and
      stabilising renal function in children with severe uropathy. METHODS:
      Retrospective case note review. RESULTS: Nineteen patients underwent temporary
      cutaneous vesicostomy over a 12-year period. Of these, 10 had a prenatally
      detected uropathy. Children with prenatal findings were diverted at a
      significantly younger age than cases presenting clinically (33 (range 10-240) vs.
      182 days (range 28-425), p = 0.02). In addition, there were significantly more
      boys diverted in the prenatally detected group (p = 0.02). The majority of
      clinically presenting infants were diverted because of severe or recurrent
      urosepsis whereas most prenatally detected cases underwent surgery for
      progressive renal impairment. In both groups vesicostomy was successful in
      preventing further urosepsis and resulted in improved renal function. Follow-up
      data, however, revealed 9 (50%) of 18 patients with chronic renal failure. One
      patient died prior to stoma closure from septicaemia and renal disease.
      CONCLUSIONS: The timing and indications for vesicostomy may be changing in the
      light of prenatal diagnosis. Temporary vesicostomy diversion remains a simple,
      effective and easily reversible method of preventing urosepsis and stabilising
      upper tract function. The poor renal outcome on follow-up may reflect the fact
      vesicostomy is reserved for infants and children with severe disease.

PMID- 9612687
TI  - Ureteral valves associated with ureteral stricture. Report of 4 cases.
AB  - Ureteral valves with ureteral strictures are rare and the differential diagnosis
      is difficult to establish. Four cases are reported to present these aspects.

PMID- 9612688
TI  - Androgen receptor expression, proliferation index and aneuploidy in tissue
      explant cultures derived prostate carcinoma cells co-cultivated on membranes.
AB  - OBJECTIVES: An improved explant cell culture technique to avoid selection of
      prostatic adenocarcinoma cells toward diploid cells is described. MATERIAL AND
      METHODS: 21 prostatic carcinoma specimens which were obtained from 13 primary
      prostatic adenocarcinomas after radical prostatectomy were cultivated. Ploidy of
      the cells was monitored by fluorescence in situ DNA hybridization using the
      centromere-specific DNA probes pUC1.77, p alpha 7t1 and pY3.4. Phenotypic
      examination of androgen receptor (AR) expression was performed simultaneously
      with immunostaining by Ki-67 as proliferation marker to identify androgen
      independent growing cell clones. RESULTS: Interestingly, a high aneuploidy rate
      of the cell cultures was found with maintenance of aneuploidy in 18 (86%) of the
      21 paraffin-embedded cancer tissue specimens with proved aneuploidy. Significant
      aneuploid cell populations were retained up to a maximum of ten transfer steps.
      During serial transfer of tumor pieces the aneusomic fraction slightly decreased
      as well as the percentage of AR/Ki-67-positive cells. CONCLUSIONS: The presented
      in vitro model allows to study the proliferation of genetically abnormal cells
      with respect to hormone dependency in a paracrine situation.

PMID- 9612689
TI  - Molecular genetic alterations of c-myc oncogene in superficial and locally
      advanced bladder cancer.
AB  - OBJECTIVE: Gene activation and altered expression of cellular proto-oncogene are
      important mechanisms implicated in initiation and development processes of human
      cancer. It has already been shown that c-myc oncogene is implicated in the
      control of cell proliferation, apoptosis and differentiation. METHODS: We have
      determined the methylation status, the presence of genetic amplification and the
      presence of m-RNA overexpression of c-myc gene in 31 samples from patients with
      bladder carcinomas. RESULTS: Our data demonstrated the presence of c-myc gene
      amplification only in 5 of 15 superficial bladder carcinomas (p < 0.05). On the
      other hand, we did not find statistical significant correlation between the
      methylation, expression of c-myc gene and the clinical-histopathological
      parameters. A significant correlation (p < 0.05) was found between the
      methylation pattern and m-RNA overexpression of c-myc oncogene. CONCLUSION: We
      demonstrate aberrant c-myc gene status in human bladder cancer. This oncogene is
      altered at different levels in bladder carcinoma genesis and progression.

PMID- 9612690
TI  - [Possible function and origin of crossing over].
AB  - Crossing over to repair genetic material via exchange probably emerged at the
      initial stages of organic evolution, earlier than the appearance of the DNA
      molecule in its present form. In that period, nitrous bases existed as free
      molecules, although, like in double-helical DNA, they formed aggregates. The
      electrochemical characteristics of pyrimidines differ from one another to a
      greater extent than those of purines, which are almost electrically neutral.
      Therefore, it is possible that the DNA electrostatic balance is accounted for by
      nonspecific interaction between pyrimidine bases. The data obtained by Nussinov
      et al. indicate that, in homooligomers, the arrangement of pyrimidine bases in
      opposite DNA strands exhibits some restrictions with respect to their mutual
      positions. In functioning DNA, the electrostatic balance of pyrimidine
      arrangement in complementary strands may favor rapid transitions of the molecule
      between an open helix and the original state. It is supposed that crossing over
      restores the electrostatically balanced spatial arrangement of pyrimidine
      homooligomers and, hence, the functional activity of the entire DNA molecule.

PMID- 9612691
TI  - [Mutation bursts of the yellow gene in a natural Drosophila melanogaster
      population is connected with insertion of the hobo transposon].
AB  - In 1981, a recurrent local burst of high mutability and high allele frequency of
      the yellow gene was recorded in the natural population of Drosophila melanogaster
      from Uman', Ukraine. A detailed genetic analysis showed that hypomorphic alleles
      y2 prevailed during the mutation burst. Mutations were strictly allele-specific
      and occurred only in two directions: from y2 to y+ and from y+ to y2. Alleles y2
      isolated from the natural population differed in the degree of instability of
      mutant and wild-type derivatives, expression of the mutant phenotype, and
      complementation properties. In this work, the insertion nature of all unstable
      alleles derived from the natural population is confirmed by direct molecular
      methods. The mutation burst at the yellow locus is shown to result from insertion
      of a defective hobo copy. Six mutations y2 independently isolated from the
      natural population were caused by an insertion of hobo in the same site of the
      yellow regulatory region. The hobo copies were identical according to the
      restriction map. In three y2 alleles, the mutant phenotype was associated with
      inversion between hobo copies, one of which was located in the yellow locus and
      the other, in another unidentified region of the X chromosome. The remaining y2
      alleles were associated with deletions that were located in the vicinity of the
      hobo insertion site and in the region of yellow enhancers.

PMID- 9612692
TI  - [Cloning and structure-function analysis of the human S26 ribosomal protein
      gene].
AB  - Gene HRPS26 encoding the S26 human ribosomal protein has been sequenced. Gene
      HRPS26 consists of four exons and three introns. Its size is 2027 bp; the size of
      its mRNA is 438 nucleotides. As most of the genes of ribosomal proteins of
      vertebrates, the HRPS26 gene has a short first exon, which corresponds to the 5'
      untranslated region of mRNA; the origin of transcription is located in the
      polypyrimidine tract. The functional activity of the cloned HRPS26 promoter
      region has been confirmed by transcription of hybrid plasmids in HeLa cells.

PMID- 9612693
TI  - [Selection for sex behavior changes the metabolism of juvenile hormone in
      Drosophila melanogaster].
AB  - The metabolism of juvenile hormone (JH) was studied in two lines of Drosophila
      melanogaster selected for differences in mating behavior. The lines were tested
      under normal conditions and after short-term heat shock. Females of the HA line
      (selected for high male mating activity) were shown to exhibit a high level of JH
      hydrolyzing activity under normal conditions. By contrast, females of the LA line
      (selected for low male mating activity) and males of both lines had a low level
      of JH hydrolysis. Stress exposure resulted in a decrease of JH hydrolysis in
      females of the HA line; this effect was absent in females of the LA line and
      males of both lines.

PMID- 9612694
TI  - [Genetic variability of Trichinella spiralis Oven, 1835, and Trichinella
      pseudospiralis Garkavi, 1972, detected by polymerase chain reaction with random
      primers].
AB  - DNA polymorphisms in two parasitic nematode species, Trichinella spiralis Oven,
      1835, and Trichinella pseudospiralis Garkavi, 1972, were revealed via random
      amplification of polymorphic DNA by the polymerase chain reaction (RAPD PCR). The
      diagnostic value of seven 10-bp oligonucleotide primers was evaluated, and the
      extent of the homology between the genomes of the two species was estimated. The
      intraspecific variation of RAPD markers was revealed in larvae of both species
      isolated from experimentally infected white rats. The variation was higher in
      larvae from nonlinear rats than in larvae from linear rats. When animals were
      infected with both Trichinella species simultaneously, "hybrid" progeny were
      obtained that had capsule that somewhat differed in shape from one characteristic
      of the parental species, T. spiralis. In RAPD spectra, the hybrids showed higher
      similarity of T. spiralis than to T. pseudospiralis. Intra- and interspecific
      differentiation, genome divergence, and factors inducing the intraspecific
      variation in Trichinella species are discussed.

PMID- 9612695
TI  - [Characteristics of the gene pool of Russian Old Believers in Siberia based on
      polymorphism of blood groups, isoenzymes, and blood proteins].
AB  - The frequency distributions of A1A2B0, Rhesus, MNSs, P, Duffy, Kell, Hp, Tf, AcP,
      PGM1 alleles, and haplotypes were studied in Siberian populations of Old
      Believers (Burnyi village, Krasnoyarskii krai, and Isetskii raion, Tyumenskaya
      oblast) and in ethnic Russians from Tyumenskaya oblast. Features characteristic
      of the genetic structure of these groups were revealed. The Siberian groups of
      Russians were shown to be genetically removed from European Russian populations
      (Tverskaya and Vologodskaya oblasts). The Burnyi population of Old Believers was
      significantly removed from the other groups of Russians due to peculiarities in
      the sample.

PMID- 9612696
TI  - [Polymorphism of restriction sites of a control region of mitochondrial DNA in
      populations of Russian Old Believers and migrant slavic inhabitants of northern
      Siberia].
AB  - Restriction fragment length polymorphism (RFLP) was studied in restriction sites
      AvaII, BamHI, EcoRV, KpnI, HaeIII, and RsaI of the mitochondrial DNA (mtDNA) D
      loop in populations of Old Believers (Starovery) and in Slavic migrants in
      northern Siberia. Frequencies of rare variants of all polymorphic sites studied
      were estimated. The results were compared with the published data on mtDNA
      polymorphism sites studied were estimated. The results were compared with the
      published data on mtDNA polymorphism in Russian populations of central and
      southern Russia and in other Eastern Slavic, Caucasoid, and Mongolian
      populations. Significance of interpopulation differences with respect to
      distributions of variants of polymorphism sites was estimated with the use of the
      chi2 test. The comparison did not reveal significant differences between any
      groups of Eastern Slavs, including Old Believers. However, they significantly
      differed from both Mongols and Europeans (P < 0.05). To date, stable estimates of
      the polymorphism level in most of the restriction sites have been obtained for
      the Russian population. Regarding the distribution of the restriction-site
      variants of mtDNA, Russians significantly differ from the total European
      population, as well as from Mongols. In the populations of Old Believers, the
      effect of isolation on the diversity of the mitochondrial genome was
      demonstrated.

PMID- 9612697
TI  - [Genogeographic primary hypolactasia in the Old World populations].
AB  - The geographic distribution of primary hypolactasia (i.e., the genetically
      determined (LAC*R), age-dependent decrease in lactase activity, which is
      phenotypically expressed as the intolerance to whole milk), was studied. Data on
      the distribution of primary hypolactasia and the LAC*R gene frequencies in
      populations of the Old World are analyzed, with special emphasis on LAC*R
      distribution in Russia. New data on populations of Kildin Saamis, Mordovian
      ethnic groups (Mokshas and Erzyas), Udmurtians, Komi-Permiaks, Komi-Zyrians (Komi
      Izhem ethnographic group), Northern (Sos'va) Mansis, Northern Khantys, and
      Russians are described. Gene geographic maps of the LAC*R gene's distribution in
      populations of the Old World, Europe, and the Ural region were constructed. A map
      reflecting the amount of the original information on different regions and,
      therefore, the reliability of the gene geographic maps, is given. In Europe, the
      interpopulation diversity Gst of the LAC*R gene was significantly higher (0.169)
      than the average diversity of the European gene pool. The high variation was
      assumed to result from a potent differentiating selection that affects the gene
      for primary hypolactasia.

PMID- 9612698
TI  - [Distribution among Europeans of types of mitochondrial DNA, detected in putative
      remains of Tsar Nicholas II].
AB  - The prevalence of two types of the mitochondrial DNA (mtDNA) control region
      defined in the members of the Russian Czar family was examined in Caucasoid
      populations (N = 1081). The frequency of the type 16126(C)-16294(T)-16296(T) in
      Caucasoids was less than 1%. The mitotype 16126(C)-16169(T)-16294(T)-16296(T) was
      not found in the populations studied.

PMID- 9612699
TI  - [Genetic analysis of Saccharomyces castellii, S. exiguus and S. martiniae
      yeasts].
AB  - Genetic lines of three biological yeast species of the Saccharomyces sensu lato
      group--S. castellii, S. exiguus, and S. martiniae--were created. Homo- and
      heterothalmic monosporic fertile strains were marked by different auxotrophic
      mutations. Conditions for the hybridization of the Saccharomyces sensu lato yeast
      were established. The mating of spores or haploid cells of auxotrophic
      complementary mutants was performed on the complete YPD medium. Prototrophic
      diploid hybrids were selected on a minimal medium. In S. castellii, the
      hybridization of diploid cells was demonstrated. All three species studied were
      suitable for tetrad analysis.

PMID- 9612700
TI  - [Cloning the BR-C gene in Drosophila virilis].
AB  - In 1980, Belyaeva et al. found in Drosophila melanogaster the ecs (ecdysterone
      sensitivity) locus, later designated BR-C (Broad-Complex). This locus plays a key
      role in the reaction cascade of ecdysterone-regulated development. The gene BR-C
      was cloned by Chao and Guild (1986) and Belyaeva et al. (1987). To conduct
      "walking along the chromosome" in Drosophila virilis, cloned sequences of the BR
      C gene from D. melanogaster were used as probes, hybridizing the start sites. A
      fragment of about 100 kb containing BR-C of D. virilis was cloned. A restriction
      map of the cloned region was created.

PMID- 9612701
TI  - [Transcriptional activity of the BR-C locus in Drosophila virilis].
AB  - The locus BR-C, responsible for cell reaction to the hormone ecdysterone in
      Drosophila virilis, was previously cloned and mapped. This locus occupies a
      region of about 100 kb. To define exon location and a mode of D. virilis BR-C
      expression at different stages of development (embryos; first, second, and third
      instar; early, middle and late pupae; adult flies), Northern blot hybridization
      was conducted. Poly(A)+ RNA, isolated from D. virilis flies at these
      developmental stages, was hybridized with fragments of the BR-C locus DNA. This
      D. virilis gene was shown to encode at least six different transcripts that were
      10, 5.5, 4.4, 3.8, 3.3, and 2.7 kb in size. The highest gene expression is
      attained at the second and third instar and at the late pupa stage.

PMID- 9612702
TI  - [The question of nomenclature of kappa-casein in representatives of the Bovinae
      family].

PMID- 9612703
TI  - [New functional imaging technique "positron emission tomography"].
AB  - A new functional imaging technique, positron emission tomography (PET) has been
      introduced to probe biochemical imaging in vivo using physiological tracers, such
      as carbon-11, nitrogen-13, oxygen-15 and fluorine-18. This technique has been
      used for quantitative assessment of regional blood flow, metabolic rates, and
      various neurotransmission-receptor functions in the brain, myocardium, and
      various tumor tissues. Among them, F-18 fluorine labeled fluorodeoxyglucose (FDG)
      has been most widely used to assess exogenous glucose utilization. Recent
      experimental studies indicated that glucose metabolism is increased with enhanced
      glucose transporter gene in malignant tumors, PET with FDG has been used to
      assess tumor imaging. This technique has been shown to be useful for (1) early
      detection of malignant tumors, (2) differentiation of malignant from benign
      tumors, (3) staging of the tumor, (4) assessment of treatment effect, and (5)
      early detection of recurrence of tumors. In this review article, clinical values
      of PET in oncology has been introduced and summarized.

PMID- 9612705
TI  - [Management for osteoporosis in a society composed largely of elderly people-
      from a practical orthopaedic point of view].
AB  - Aging of Japanese population in recent years is advancing at unexpected speed.
      The incidence of osteoporosis and fracture increase rapidly with aging of the
      population. Since 1970, at opening of our department, I have expected that a
      society would be composed largely of elderly people. To prevent elderly people
      from being beg-ridden and demented, I have made efforts to prevention and
      treatment of osteoporosis. Purpose of this paper is to show concerning the
      screening of osteoporosis in this area of Hakodate city and southern part of
      Hokkaido, and to report our treatment for osteoporosis. There are many ways of
      measuring bone mineral density (BMD), and dual energy X-ray absorptiometry (DEXA)
      is the simplest and the most accurate. Concerning of diagnosis of osteoporosis,
      we investigated the change of the BMD after hip surgery. On the other hand, we
      also reported the effectiveness of Vitamin-K for osteoporosis. No studies have
      ever been tried to clarify about this treatment. We are making efforts to
      enlighten the people on prevention, early diagnosis and treatment of
      osteoporosis.

PMID- 9612704
TI  - [Development of targeted chemoradiotherapy for malignant melanoma by exploitation
      of metabolic pathway].
AB  - Malignant melanoma cell possesses a unique metabolic pathway which consists of
      conversion of tyrosine, an essential amino acid, to dopa and subsequently to
      dopaquinone in the presence of tyrosinase to form melanin, the end product of the
      metabolic pathway. This tyrosinase-mediated melanin biosynthesis occurs within
      normal melanocyte and its transformed cell, malignant melanoma cell. It is in
      general highly elevated in malignant melanoma cells compared to normal
      melanocytes. The objective of our research is to develop targeted therapeutic
      approach for malignant melanoma by utilizing this unique metabolic pathway in the
      presence of tyrosinase. Specifically we have synthesized sulpher homologue of
      tyrosine, cysteinylphenol and its amine derivative, cysteaminylphenol (CAP) and
      subsequently its N-acetyl and N-propionyl derivatives (N-acetyl and N-propionyl
      CAP). These synthetic compounds are good tyrosinase substrates and possess high
      lipophilicity and penetration through the plasma membrane into melanoma cells.
      Our in vivo and in vitro studies using these synthetic compounds revealed
      following findings: (1) CAP and its derivatives possess selective cytotoxicity to
      human neoplastic cells, in particular tyrosinase-positive melanoma cells; (2) N
      Acetyl-CAP and N-propionyl-CAP possess both cytostatic and cytocidal effect; (3)
      These synthetic compounds provide irreversible DNA damage to melanoma cells with
      high tyrosinase activity; (4) However, there is no irreversible DNA damage to non
      pigmented, tyrosinase negative cells; (5) Pharmacological effect of CAP appears
      to be related to oxidative stress; (6) Radio-labelled CAP derivatives showed
      selective incorporation into melanin-forming melanoma cells; (7) This selective
      cytotoxicity can occur in non-melanin forming cells after transfection of human
      tyrosinase cDNA, resulting cytocidal effect. All these findings clearly indicate
      that our synthetic compounds which are good substrates of human tyrosinase can
      provide basis for the development of targeted chemotherapy and/or
      chemoradiotherapy. In addition the transfection of human tyrosinase cDNA will
      provide the rational approach for developing the targeted gene therapy to non
      melanoma cells.

PMID- 9612706
TI  - Effects of volatile anesthetics on respiratory activity and chemosensitivity in
      the isolated brainstem-spinal cord of the newborn rat.
AB  - To elucidate the various actions of volatile anesthetics on respiratory activity
      and chemosensitivity, we have studied the activities of the respiration-related
      structures in the medulla of the in vitro brainstem-spinal cord preparation of
      the newborn rat. Halothane decreased respiratory burst frequency (fR),
      inspiratory duration (Ti), integrated ventral C4 root activity (integral of C4)
      and respiratory minute activity (RMA) in a concentration-dependent fashion.
      Bicuculline counteracted the depressive effect of halothane on fR, integral of
      C4, and RMA. Inspiratory neuronal activity recorded at the rostral ventrolateral
      medulla (RVL) corresponded to these changes. Activities of Pre-Inspiratory (Pre
      I) neurons and expiratory neurons in the RVL were also inhibited by halothane.
      The C4 activity did not always correspond to Pre-I neurons' discharge. In this
      comparative study of three volatile anesthetics, the inhibitory effect on fR
      appeared to be greater with enflurane than with halothane or isoflurane. The
      reversal effects of bicuculline on decreases in fR, integral of C4, and RMA also
      seemed to be greater with enflurane than with halothane or isoflurane.
      Hypercapnia (pH 7.0) induced a significant increase in fR and RMA, and a
      significant decrease in Ti. Although halothane inhibited overall activities,
      chemo-responsiveness to hypercapnia changed similarly even during halothane
      application. Hypocapnia (pH 7.8) significantly decreased fR, and increased
      integral of C4 and Ti. Hypocapnia during halothane application also induced a
      significant decrease in fR and RMA. These results suggest that the modification
      of GABAA receptor-mediated neurotransmission is in part responsible for the
      respiratory depression by volatile anesthetics, affecting especially fR, integral
      of C4, and RMA. Low respiratory rate by enflurane is associated with GABAergic
      modification. Prolongation of Ti by enflurane, seen clinically, does not seem to
      be either central or GABAergic. These findings demonstrate the responsiveness to
      CO2 and the respiratory compensation mechanism via respiratory frequency in the
      isolated preparation. It is, furthermore, indicated that halothane preserves the
      central chemosensitivity while its concentration is high enough to reduce the
      respiratory activities.

PMID- 9612707
TI  - Cost analysis of treatments for severe combined immunodeficiency patients caused
      by adenosine deaminase deficiency: comparison of gene therapy and bone marrow
      transplantation.
AB  - In order to perform a cost assessment of treatment for severe combined
      immunodeficiency patients caused by adenosine deaminase deficiency, we estimated
      the cost for 3 successfully treated patients in Japan for whom related HLA
      identical bone marrow donors could not be found. One patient received gene
      therapy and the other 2 patients received HLA-haploidentical bone marrow
      transplantation. The medical costs required for hospitalization periods for gene
      therapy and bone marrow transplantation were estimated respectively by analyzing
      the monthly bills that were calculated based on the fee schedule covered by
      health insurance. In the gene therapy, the total cost was calculated by adding
      the charges not covered by health insurance. The gene therapy and transplantation
      patients had significant differences in terms of cost structure and total cost.
      The items concerning "procedures" associated with gene transduction in the former
      amounted to 47.8% of the total cost, and "medication" in the latter amounted to
      34.3% and 31.9% respectively. The items concerning "hospitalization" amounted to
      a large percentage in both treatments. The total cost was estimated at
      approximately 18.9 million yen for gene therapy, and 7.4 million yen and 10.5
      million yen for transplantation. These results obtained through this study
      revealed the cost structure of gene therapy in comparison with transplantation.
      This report represents the first step to the assessment of medical technology of
      human gene therapy, in terms of medical cost, in which a stable and favorable
      therapeutic outcome was achieved.

PMID- 9612708
TI  - [Induction of neutralizing antibodies against HIV-1 viruses in HLA-DQ6 mice by
      peptide vaccines].
AB  - A non-immunogenic peptide in mice bearing a certain MHC molecule can be rendered
      immunogenic, when the peptide is introduced into an MHC-binding component
      (cassete theory). We applied the cassete theory to preparation of effective
      peptide vaccines. Indeed a 46F/HA127-133/54A peptide vaccine which had been
      prepared by introducing hemagglutinin (127-133) of influenza virus, A/Aich/2/68
      (H3N2), into H-2Ab-binding component derived fom pigeon cytochrom c (43-58)
      induced significant immunological responses in H-2Ab mice. In the present study
      to examine whether the peptide vaccines are effective in human positive of HLA
      DQ6 type, DQ6 mice were established as a model of HLA-DQ6 positive individuals by
      crossing HLA-DQ6 transgenic mice with murine class II knockout mice. It was shown
      that the DQ6 mice carried only HLA-DQ6 as MHC class II molecules. We then
      immunized these DQ6 mice with peptide vaccines, 46F/J2/54A or 46F/J2/54A/J2,
      which had been prepared by introducing B subtype consensus sequence (IGP-GRAF) of
      the HIV-1 V3 region (J2) into an MHC-binding component containing a supermotif
      for binding to various MHC class II molecules. An original V3 peptide including
      the consensus sequence was non-immunogenic in the DQ6 mice. In contrast, the both
      peptide vaccines induced significant T cell responses in the DQ6 mice. Antisera
      from DQ6 mice that had been immunized with the peptide vaccines neutralized not
      only laboratory B subtype strains but also several clinical isolates of E subtype
      strains of HIV-1 in vitro. From these findings, it is anticipated that these
      peptide vaccines may protect DQ6 positive individuals from infection with various
      HIV-1 variants.

PMID- 9612709
TI  - Effects of styrene exposure on middle latency auditory evoked potentials and
      glial cells in rat.
AB  - Neurophysiological and neurochemical effects of treatment with styrene at 400
      mg/kg and 800 mg/kg per day for two weeks were investigated. Significant delay in
      latencies of No, Po, Na, and Pa components of middle latency auditory-evoked
      potentials (MAEPs) was observed in dose- and time-dependent manner after
      exposure. Moreover, the peak to peak intervals of No-Po, Po-Na, and Na-Pa
      components were also prolonged in the 800 mg/kg styrene-treated group compared
      with those in both the 400 mg/kg styrene-treated group and the control. However,
      no significant change of amplitudes was observed. Furthermore, brain tissue
      damage was examined by measuring the expression of glial fibrillary acidic
      protein (GFAP) immunocytochemistry using confocal laser scanning microscopy. Both
      styrene-treated groups had a marked increase of GFAP expression in cerebral
      cortex and hippocampus compared to those in the control group. These results of
      delay in the latency and the peak to peak interval of (MAEPs) components and
      increased expression of GFAP in cerebral cortex and hippocampus indicate that the
      effects of styrene on the central nervous system were not only in
      electrophysiological changes but also in the structure of cerebral cortex and
      hippocampus.

PMID- 9612710
TI  - [An investigation of the effect of H3-H3 peptide vaccine for preventing influenza
      virus infection in DQ6 mice].
AB  - Based on the cassette theory that a core region of an immunogenic peptide is
      partially replaced with peptide fragments from various pathogens without any
      detrimental effects to their anchoring to the particular MHC class II molecules,
      we had prepared a peptide vaccine, 46F/HA127-133/54A (18mer) (YEGFS WTGVTQN
      KAKGIT), against A/Aichi/2/68 (H3N2) influenza viruses. It was shown that the
      46F/HA127-133/54A (18mer) was effective in Ab mice. In the present study, we
      first examined whether this peptide vaccine could induce neutralizing antibodies
      against other H3 subtype influenza viruses. The results suggested that 46F/HA127
      133/54A (18mer) would be effective for preventing infection with almost all H3
      subtype influenza viruses. Since it has been demonstrated that the Ab binding
      component possesses a supermotif for binding to various MHC class II including
      HLA-DQ6, we next examined whether the peptide vaccines could be applicable to
      human positive of HLA-DQ6 type, using DQ6 mice that carry DQ6 alone as MHC class
      II molecules. The DQ6 mice had been prepared by crossing DQ6 transgenic mouse
      with murine class II knock out mouse and were thus regarded as a model of DQ6
      positive individuals. In this particular experiment another peptide vaccine, H3
      H3, which was newly prepared by adding HA127-133 to the C-terminus of 46F/HA127
      133/54A (18mer) was used. It was demonstrated that the H3-H3 generated
      significant immunological responses and prevented infection with A/Aichi/2/68
      viruses in the DQ6 mice. Altogether, it is suggested that the peptide vaccine, H3
      H3, can be applicable to human positive of HLA-DQ6 type.

PMID- 9612711
TI  - [Studies on changes in trace elements of the brain related to aging].
AB  - This study was performed to determine whether trace elements in the brain are
      linked to its aging, using the senescence-accelerated mouse prone10 (SAMP10)
      established as a murine model of aging with brain atrophy and defect in learning
      and memory. First, concentrations of trace elements (zinc, copper, manganese,
      molybdenum, and rubidium) were determined by ICP-MS in 8 regions of the brain in
      male SAMP10 and in SAMR1 (control) which undergo ordinary aging, at 3, 6, 9 and
      12 months of age. Second, the release of glutamic acid and other amino acids
      related to neurotransmission was determined by microdialysis and HPLC-ECD in the
      hippocampus of SAM aged 5 and 12 months. Decreases in zinc, manganese and
      rubidium concentrations and an increase in the copper concentration with aging
      were observed in the brains of control mice. These results were similar to
      previous reports of the brain in human and rat, and indicated that these trace
      elements may be closely related to the aging process in the brain. SAMP10 had low
      levels of zinc and manganese in most brain regions in old age, and a high level
      of molybdenum in the brain with increasing age as compared to the control. A low
      level of copper was observed in the cerebral cortex of the brain in SAMP10 from
      young age. The release of glutamic acid and glycine from the hippocampus of
      SAMP10 significantly increased as compared to that of control mice at the age of
      12 months. These results showed that abnormal metabolisms of the trace elements
      and neurotransmitter are in the brain of SAMP10, and indicated that these changes
      may cause the senescence acceleration of SAMP10.

PMID- 9612712
TI  - Epstein-Barr virus.

PMID- 9612713
TI  - Kaposi's sarcoma herpesvirus/human herpesvirus 8.

PMID- 9612714
TI  - Family, clinician, and patient perceptions of coercion in mental hospital
      admission. A comparative study.

PMID- 9612715
TI  - Adult guardianship: narrative readings in the "shadow" of the law?

PMID- 9612716
TI  - Getting away with murder? Dissociative states and criminal responsibility.

PMID- 9612717
TI  - Revocation of conditional release. A comparison of individual and program
      characteristics across four U.S. states.

PMID- 9612718
TI  - The return to mens rea. Salvaging a reasonable perspective on mental disorder in
      criminal trials.

PMID- 9612719
TI  - Criminal offenses among discharged mentally ill individuals. Determinants of the
      duration from discharge and absence of diagnostic specificity.

PMID- 9612720
TI  - A case-control study on the socio-demographic characteristics of 53 neonaticidal
      mothers.

PMID- 9612721
TI  - Cytomegalovirus glycoprotein B sequence variation among Japanese bone marrow
      transplant recipients.
AB  - Glycoprotein B (gB) of human cytomegalovirus (CMV) is the major target protein of
      neutralizing antibodies, and four variant types are known. A previously reported
      polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP)
      method was modified by eliminating the cell culture step and amplifying a CMV
      fragment (corresponding to a.a. 441-450 of gB) by nested PCR. DNA was extracted
      from the sera of 27 pediatric bone marrow transplant recipients and subjected to
      nested PCR. Of the samples, 20 yielded PCR products, and the gB type was
      determined by RFLP. Of the 20 patients, 4 (20%) had gB type 1 (Towne type), 15
      patients (75%) had gB type 2 (AD 169 type), and 1 patient (5%) had gB type 3.
      Previous studies showed that gB type was most common among Caucasians [Chou and
      Dennison: J Infect Dis 1991;163:1229-1234; Fries et al: J Infect Dis 1994;169:769
      774]. Thus, gB genotypes seem to be distributed differently in Caucasians and
      Japanese. Further, nucleotide sequence analysis of the amplified region revealed
      that all the type 2 viruses had the same amino acid sequences. The type 3 sample
      had a novel amino acid substitution at position 498. Of the type 1 samples, 3 had
      amino acid substitutions in various positions: 1 sample at position 493, 1 sample
      at position 447 and 1 sample at position 452, 493 and 498.

PMID- 9612722
TI  - Ilheus virus (Flaviviridae, Flavivirus) is closely related to Japanese
      encephalitis virus complex.
AB  - The Ilheus (ILH) virus has long been known to belong to group B of the
      arboviruses. Previous attempts to relate it to existing serogroups within the
      Flavivirus genus using conventional serological techniques such as
      hemagglutination inhibition, neutralization and complement fixation tests have
      been inconclusive. We have first used denaturing gel electrophoresis to estimate
      the molecular weight of immunoprecipitated radiolabeled viral proteins and the
      cross-reactivity among ILH proteins and hyperimmune sera to several flaviviruses
      only from the mosquito-borne encephalitis virus serogroups. The estimated
      molecular weight for the three proteins was in the same order of magnitude, as
      previously established, for mosquito-borne flaviviruses. Cross
      immunoprecipitation tests showed that NS3 protein is the most cross-reactive.
      Partial nucleotide sequence analyses of the NS3 gene, corresponding to an area
      linking the helicase and the RNA triphosphatase domains, revealed that ILH virus
      is very closely related to the Japanese encephalitis virus complex confirming
      earlier serological data.

PMID- 9612723
TI  - Sequence and cognitive analyses of two virulence-associated markers of bluetongue
      virus serotype 17.
AB  - Genome segments 2 and 3 were completely sequenced for one virulent and one
      avirulent bluetongue serotype 17 (BLU-17). These two segments were previously
      shown to exhibit virulence-associated markers. The marker on segment 2 was
      characterized as a change in the neutralization domain on its protein product,
      VP2. The nucleotide sequences for segments 2 were 94.5% identical, and their
      predicted proteins differed by 34 amino acids or 3.7%. Three clusters of
      variability were identified which may be involved with viral neutralization.
      These variable regions were compared to mutations for published monoclonal
      antibody-resistant variants of BLU. The marker on segment 3 was characterized as
      a mobility shift in polyacrylamide gel electrophoresis (PAGE). The nucleotide
      sequences were 95.0% identical, and their predicted proteins differed by four
      amino acids or 0.4%. These amino acid changes were relatively conserved;
      therefore, they are not likely responsible for virulence. The segment 3 sequences
      were compared to published sequences, and evidence was found to suggest that the
      virulent isolate had naturally reassorted between a BLU-17 and BLU-10 isolate.

PMID- 9612724
TI  - Detection of human papillomavirus type 16 DNA and of antibodies to human
      papillomavirus type 16 proteins in children.
AB  - We have measured markers of human papillomavirus type 16 (HPV 16) infection in
      children (1-10 years of age) who were hospitalized for reasons unrelated to
      papillomavirus infection. Genital and buccal swabs obtained from 79 children were
      tested for the presence of HPV 16 DNA by PCR. Low-level positivity was found in
      34 donors, twice as often in oral than in genital swabs. There was no sex
      specific difference, but there was a trend towards a higher positivity rate with
      young age. Serum antibodies (IgG) were measured by ELISA based on peptides
      derived from the HPV 16 early proteins E4 (one peptide), E6 (two peptides) or E7
      (two peptides) in 75 children and by ELISA based on virus-like particles in 66
      children. Low-positivity rates were found for E6 (5.1%), E7 (2.5%) or capsid
      proteins (1.5%), but 20.3% of the sera reacted with the E4-specific peptide.
      There was no correlation between sero-positivity and the detection of HPV 16 DNA.
      In those instances where HPV DNA positivity in young children represents true
      infection and not environmental contamination, we speculate that this infection
      is accompanied by low-level virus replication that does not induce a measurable
      antibody response. Reactivity to the E4 protein is likely due to cross-reacting
      antibodies directed either against E4 proteins of other HPV types or against
      unrelated antigens.

PMID- 9612725
TI  - Highly infectious purified preparations of disease-specific amyloid of
      transmissible spongiform encephalopathies are not devoid of nucleic acids of
      viral size.
AB  - An efficient purification protocol for infectivity causing a transmissible
      spongiform encephalopathy (TSE) is described. From fractions purified by this
      protocol about 3 x 10(8) LD50 but only 3 ng of nucleic acids per gram of brain
      material can be isolated from all TSE-affected brains (hamster, human, sheep,
      cattle). By PAGE such fractions from brains of infected and control hamsters
      contained only one distinct nucleic acid band of 1.5 kg together with some
      broader smear of nucleic acid material. Although distilled water was used for
      such purifications, quite often a similar nucleic acid band was isolated from
      blanks containing no brain material. In all instances this material proved to be
      DNA. The result challenges the potentially important claim that purified
      infectious preparations of TSE-specific amyloid are free of nucleic acids of
      viral size. Nucleic acids isolated by other groups from diseased brain were not
      detected in preparations isolated by the new protocol. The application of this
      purification protocol in future studies will be helpful to decide whether TSEs
      are caused by agents containing nucleic acid or by protein only.

PMID- 9612726
TI  - Human disease caused by an arbovirus closely related to Ilheus virus: report of
      five cases.
AB  - We report five cases of human disease caused by arbovirus in 5 patients from the
      State of Sao Paulo, Brazil, residing in the municipalities of Osasco, Atibaia,
      Guaruja, and the capital Sao Paulo, respectively. One of the patients resides in
      Sao Luis, capital of the State of Maranhao. The sites of infection probably were
      the states of Parana and Goias, both in cave regions, the State of Amazonas, and
      Rondonia in two cases. Laboratory tests for malaria were negative and 1 patient
      showed a positive serum reaction for leptospirosis. Serum samples from the acute
      and convalescent phases were tested by hemagglutination inhibition, complement
      fixation, and neutralization in mice. Acute phase samples were inoculated into
      suckling mice by the intracerebral route. A close antigenic relationship was
      observed between the five agents isolated and the flavivirus Ilheus. Serologic
      tests demonstrated the absence of antibodies in all samples from the 5 patients
      during convalescence and even for more than 1 year after infection in 1 of them.

PMID- 9612727
TI  - Sequence analysis of the terminal protein precursor coding regions from bovine
      adenovirus serotypes 2 and 3.
AB  - As part of our efforts to develop bovine adenoviruses into a vector system, we
      sequenced the region predicted to encode the terminal protein precursor of either
      bovine adenoviruses type 2 and bovine adenoviruses type 3. We examined the
      regions containing the terminal protein precursors and showed that the bovine
      adenovirus early region 2B had an identical organization to all adenoviruses so
      far examined. The bovine adenovirus terminal protein precursors and those of
      other adenoviruses were also compared in a sequence alignment analysis and
      several highly conserved structural domains were identified. Finally, we showed
      how the various terminal protein precursors were related in a sequence pair
      similarity analysis and concluded that the terminal protein precursors of bovine
      adenoviruses types 2 and 3 are significantly different from each other at the
      protein sequence level.

PMID- 9612728
TI  - Increased serum and mRNA levels of RANTES associated with elevated levels of
      activated CD8+CD38+ T cells in HIV-1 infected individuals.
AB  - The serum levels of the beta-chemokine RANTES and, albeit less, MIP-1 beta were
      found to be increased in 37 HIV-1 infected compared to seronegative individuals.
      In contrast the serum levels of IL-16 were only sporadically elevated in
      seropositives as well as in seronegatives. Concomitantly, the RANTES gene
      expression increased about tenfold in seropositives, whereas the MIP-1 beta and
      IL-16 mRNA levels were not elevated. No correlation between the increase of the
      MIP-1 beta and RANTES serum concentrations and the plasma virus load, the number
      of the peripheral CD4+ T cells or the therapy status of the patients was found.
      However, the increased proportion of activated CD8+CD38+ T cells in the
      peripheral blood of all seropositives paralleled the increased RANTES serum
      levels detected indicating that immune activation in HIV-1-infected individuals
      may contribute to increased RANTES serum levels.

PMID- 9612729
TI  - Retroviral-mediated expression of FIV envelope/Rev induces CD8+ CTL responses in
      mice.
AB  - Recombinant retroviral vectors that express the Env and Rev proteins of feline
      immunodeficiency virus (FIV) were prepared and analyzed in a mouse model system
      for their ability to induce antigen-specific CD8+ CTL (cytotoxic T lymphocyte)
      responses. The ultimate goal of these studies is to develop effective immunogens
      for CTL induction in the cat. Recombinant Env/Rev retroviral vectors were used to
      transduce mouse fibroblasts and these cells were then inoculated
      intraperitoneally into syngeneic BALB/c mice. FIV Env-specific CTL responses were
      obtained. The potent ability of recombinant retroviral vector-transduced cells to
      elicit cell-mediated immunity in the mouse model offers the possibility that such
      delivery systems may serve as therapeutic and/or prophylactic treatments against
      FIV infection in the cat.

PMID- 9612730
TI  - High percentage of seronegative HCV infections in hemodialysis patients: the need
      for PCR.
AB  - Among patients undergoing maintenance hemodialysis, a high prevalence of
      hepatitis C virus (HCV) infection can be observed. In a prospective study, sera
      of 273 patients were examined for the presence of HCV infection by serological
      tests and by PCR. Thirty-five patients (12.8%) were HCV antibody positive, and in
      31 of them HCV RNA could be detected by PCR. Among the 238 seronegative patients
      HCV infection was detected in 12 cases (5.0%) exclusively by PCR. Only in 1 of
      these patients seroconversion could be observed within the 18-month follow-up
      period. These findings demonstrate that in hemodialysis patients PCR is necessary
      for the diagnosis of HCV infection.

PMID- 9612731
TI  - The first Flaviviridae symposium.
AB  - The first annual Flaviviridae Symposium, sponsored by ICN Pharmaceuticals Inc.,
      was held in Lyon, France, on 9 October, 1997, to communicate current
      understanding on the Flaviviridae. This multidisciplinary symposium attracted
      over 300 international delegates and presentations covered virology, viral
      pathogenesis, potential therapies and strategies for vaccine development. The
      symposium reviewed the research area that may lead to the discovery and design of
      human and veterinary medicines against members of this virus family.

PMID- 9612732
TI  - Synthetic real estate: bringing corporate finance to health care.
AB  - The changing landscape of health care has caused hospitals, health care systems,
      and other health care organizations to look for ways to finance expansions and
      acquisitions without "tainting" their balance sheets. This search has led health
      care executives to a financing technique that has been already embraced by
      Fortune 500 companies for most of this decade and more recently adopted by high
      tech companies: synthetic real estate. Select case studies provide examples of
      the more creative financial structures currently being employed to meet rapidly
      growing and increasingly complex funding needs.

PMID- 9612733
TI  - Medicare's new capitation method.
AB  - The method used to determine capitation rates for Medicare risk-bearing health
      plans changed on January 1, 1998. The new approach establishes a minimum rate
      that is substantially higher than the amounts Medicare previously paid in most of
      the nation's counties, reduces the volatility in the rates, and guarantees all
      participating health plans at least a 2 percent annual rate increase for the next
      several years. It is hoped that the methodological improvements will motivate
      more health plans to become Medicare contractors.

PMID- 9612734
TI  - Hospital finance.
AB  - This article summarizes key areas of focus for the analysis of risk in the
      hospital segment of the health care industry. The article is written from a
      commercial bank lending perspective. Both for-profit (C-corporations) and 501
      (c)(3) not-for-profit segments are addressed.

PMID- 9612735
TI  - Performance under capitation: the true cost of infrastructure.
AB  - Administrative costs are a major item of concern for capitated provider groups,
      who must maintain a sophisticated infrastructure to allow them to manage and
      deliver clinical care to their patients under a fixed budget. The cost of this
      infrastructure is under steady upward pressure, as HMOs delegate more activities
      to providers and step up their reporting requirements. Our experience in
      establishing an infrastructure for a provider network is reported, and indicates
      substantial costs for both start-up and ongoing operations, which are highly
      volume dependent. A powerful case exists in favor of centralizing and pooling
      administrative infrastructure across related provider groups.

PMID- 9612736
TI  - Banking: financing trends in an acquisitive health care market--focus on long
      term care.
AB  - This article reviews the long-term care sector of the health care industry,
      particularly the factors driving sector consolidation and, through the use of
      four transactions as a platform, discusses key credit issues and risks facing
      long-term care companies.

PMID- 9612737
TI  - Credit analysis of nonprofit continuing care retirement communities.
AB  - The continuing care retirement community (CCRC) industry's growth has gained the
      attention of the financial community. As the industry's financial and regulatory
      environments change, credit analysts are developing analytical tools to evaluate
      these changes. The following article discusses some of these tools, provides a
      sample credit profile of a CCRC, and reviews recent accounting changes that will
      affect CCRC credit analysis.

PMID- 9612738
TI  - Charitable remainder trust strategies for health care organizations.
AB  - While availability of tax-exempt financing and exemption from income and property
      taxes have been viewed as the primary benefits of tax exemption, an underutilized
      benefit is the eligibility to receive charitable contributions. This article,
      using acquisition of a medical practice as an example, demonstrates one way
      planned giving can benefit both the health care organization and its physicians,
      and how such giving programs can be tailored to individual donor needs. Rather
      than selling a medical practice directly to a hospital, both the physician and
      the tax-exempt health care organization realize greater benefits through the
      illustrated charitable remainder trust strategy.

PMID- 9612739
TI  - Service-line management/bottom-line management.
AB  - To survive in the sturm und drang of health care administration, hospitals and
      health care systems will have to restructure themselves in ways that emphasize
      their specific clinical strengths, control their costs, and manage the delivery
      and outcomes of care. Structuring the organization along clinical lines of
      service (e.g., oncology, cardiology, rehabilitation) cedes total bottom-line
      authority for all aspects of that service to the service, or product, line
      manager. This article discusses the qualifications, compensation, and
      responsibilities of service-line managers in well-integrated health care systems
      and describes how they and managed care organizations view each other. It also
      suggests which organizations will, and will not, benefit from restructuring along
      service lines.

PMID- 9612740
TI  - Policy implications of physician income homeostasis.
AB  - Physicians tend to protect their desired target incomes in the face of declining
      fees by working more. This homeostatic "volume response" in the name of income
      protection can have budgetary consequences opposite of those intended: overall
      spending will probably rise. This is seen because when the physician tries to
      earn one extra dollar, he or she causes many additional dollars to be spent
      within the health care economy. The fraction of total costs represented by the
      physician's fee varies among specialties and procedures. Among certain medical
      services that are susceptible to doctor-induced demand, the Medicare standard
      physician payment may represent 10 percent or less of the total cost of that
      service. Accordingly, even if physicians were very inefficient at finding
      additional work to compensate for lower fees, cutting physician payments may
      still lead to increased spending. For example, a 50 percent decrease in the
      physician payment for a single operation, total hip replacement, may trigger
      nearly one billion dollars in additional annual Medicare spending, even if
      surgeons can find only half of the additional work they would need to neutralize
      the effect of the fee reduction. A sophisticated health care spending policy
      would recognize that cutting fees induces volume increases. It would recognize
      that such fee decreases without controls on the volume response will lead to
      increases in overall costs. Finally, it would recognize that the fiscal effect of
      the volume response varies between specialties and procedures, and thus flexible
      guidelines are in order.

PMID- 9612741
TI  - Corporate compliance plans in health care organizations: a top-down perspective.
AB  - Recently, at an all-day professional meeting that was targeted at about 100
      junior-level health care financial professionals, we covered a whole spectrum of
      subjects. We covered topics ranging from the Hill-Burton Act to Medicare managed
      care organizations (MCOs) and capitation; the Stark rules on physician self
      referral; the financial incentives within various payment systems for physicians,
      hospitals, and other providers; Medicare fraud and abuse rules; and the need for
      well-designed corporate compliance plans. After responding to a number of the
      participants' questions, I could not help but be reminded of the students every
      semester who ask me, "Will this be on the test?" In other words, if there are no
      real teeth in the subject, then they have too many other urgent priorities
      demanding their attention to give the issue serious consideration. Perhaps this
      highlights the need for taking corporate compliance planning seriously--starting
      at the top levels of the organization. It is well documented that leadership
      attitudes filter downward in any organization. If change for the better is going
      to take place in the area of corporate compliance, it needs to begin with each of
      us as individuals, from the top down.

PMID- 9612742
TI  - [Risks for travelers].

PMID- 9612743
TI  - [Pathology related to altitude].
AB  - Low atmospheric pressure at high altitude causes a reduction of partial oxygen
      pressure in the air. Resulting hypoxia triggers adaptive mechanisms to maintain
      oxygen delivery to cells at levels compatible with requirements of the body.
      Hyperventilation and tachycardia followed by polyglobulia are the main
      physiological responses. Hypoxia-related events can lead to edema of certain
      organs. Acute mountain sickness, high altitude pulmonary and cerebral edema are
      potentially serious disorders in remote areas. Since the only remedy is
      descending to lower altitudes, early recognition of symptoms while return is
      still possible is important. Use of a portable hyperbaric chamber can be an
      alternative if return is impossible. The potentially serious consequences of
      these diseases and poor effectiveness of treatment modalities underscore the need
      for prevention. The main preventive measures are screening to identify subjects
      at risk and providing information to mountaineers.

PMID- 9612744
TI  - [Tropical climate pathology].
AB  - In addition to being a determinant factor for the development of infectious and
      parasitic diseases, tropical weather conditions can have harmful effects for the
      human organism different from those of temperate climates. Adverse effects can
      result from aggressive environmental factors such as ultraviolet radiation,
      extreme heat, abrupt changes in temperature, and tropical storms. In weather
      sensitive subjects, exposure to tropical conditions increases the risk of acute
      reactions including ischemic heart disease, asthma attacks, and kidney stones.
      Adverse effects can be enhanced by suddenness of change in climate as underlined
      by the stress experienced by air travelers. In practice it is important to
      recognize that different tropical climates have different effects on health.
      Intertropical climates range from dry and rainy areas to plains and mountain
      areas. Knowledge of the concepts of climatopathology is necessary to advise
      patients on the choice of destination and the most favorable period for travel.

PMID- 9612745
TI  - [Travelers exposed to extreme temperatures].
AB  - Sudden introduction of the unadapted human into extreme environments can result
      in serious, sometimes fatal, reactions. Most complications are due either to
      failure of thermoregulatory system or consecutive to the physiological responses
      to those environmental conditions. In addition to a number of minor diseases,
      cold can cause two major accidents, i.e., hypothermia and frostbite which can be
      enhanced at altitude. Moreover, the main disease in altitude conditions is
      represented by the acute mountain sickness which can lead to acute pulmonary and
      cerebral edema. Heat can cause heatstroke, dehydration, syncope, and other minor
      disorders. Prevention of these manifestations during stays in inhospitable
      climatic conditions for which the body is not suited requires knowledge of the
      environment and its dangers. Implementation of suitable measures can greatly
      reduces the incidence of adverse effects.

PMID- 9612746
TI  - [Traveling with small children].
AB  - Traveling with children especially in the tropics requires special planning.
      Contraindications are rare but care providers should obtain information about
      medical and transfusional facilities at the destination. Children should receive
      all vaccinations required for international travel and for specific countries,
      taking into account age, location, duration of stay, and purpose of trip. A first
      aid kit should be packed containing a thermometer, bandages, antiseptic agents, a
      total sunscreen preparation, a mosquito net, sterile compresses, tablets for
      water disinfection, and indispensable medications (antimalarial agents,
      antipyretics, oral rehydration solutions, antiemetics, and eye wash). The main
      indication for chemoprophylaxis is malaria. Chloroquine is recommended for most
      locations but proguanil may be necessary in areas of resistance. Special
      attention must be paid to skin care in infants: maintaining cleanliness, avoiding
      cuts insofar as possible, and treating any wounds. Clothing must be carefully
      laundered and adequate to prevent overexposure to sunlight and insect bites.
      Insect bites must also be prevented by applying repellents, using mosquito nets,
      and wearing insecticide-treated garments. Handwashing by people who prepare meals
      and by the children before eating is important to prevent food poisoning. Breast
      feeding is advisable for infants. Thorough cooking of meats, rinsing of fresh
      produce, drinking of bottled beverages, and sterilization of water are also
      important food safety measures. These precautions are usually adequate to allow
      safe travel with children.

PMID- 9612747
TI  - [The elderly traveler].
AB  - An elderly traveler in good health is the same as any other traveler. However
      before departure elderly subjects should make sure that the proposed schedule of
      activities is compatible with their physical abilities. Medical counseling should
      be sought to determine that there are no conflicting health problems or physical
      impediments. Destination, itinerary, and transportation should selected
      accordingly. Immunization records should be checked and the main vaccination
      requirements for elderly subjects should be updated. To avoid running short of
      any prescribed mediation, an adequate supply for the whole trip must be packed.
      If air travel is planned, advice should be given on avoiding dehydration and
      thromboembolism. During his stay at the destination and especially in tropical
      areas, the subject should get adequate rest and guard against dehydration by
      drinking sufficiently, protecting against heat exposure, and controlling diarrhea
      promptly. Using these precautions, elderly subjects can travel as safely as
      possible.

PMID- 9612748
TI  - [Diabetes and travel].
AB  - With the continuing expansion in international air travel, increasing numbers of
      diabetic patients consult physicians for advice before going abroad. Careful
      planning is required taking into account climatic and medical conditions at the
      destination. Diabetic travelers should pack an appropriate treatment kit and
      contract special insurance coverage for medical evacuation. Precautions are
      necessary to limit the effects of motion sickness and time differences on
      diabetes control and especially the risk of hypoglycemia. Special attention is
      needed to avoid digestive problems and prevent foot injuries which can lead to
      serious complications in diabetic patients. Diabetic patients cannot forget their
      health problem during vacation and must be especially cautious when traveling.
      However with proper training, the risks of foreign travel can be reduced to
      acceptable levels.

PMID- 9612749
TI  - [Travel and renal insufficiency].
AB  - Traveling can be dangerous for subjects with kidney insufficiency. Water loss or
      septic episodes can further increase renal dysfunction. Poor diet can lead to
      hyperkaliemia. Immunosuppression not only enhances the risk of infection but also
      complicates administration of live vaccines. Some antimalarial drugs are
      contraindicated (e.g. mefloquine) and others must be used with precaution. Prior
      to departure persons requiring hemodialysis should book sessions at centers
      listed in specialized guidebooks. In addition to infection, risks for
      hemodialysis patients include thrombosis of the arteriovenous fistula in case of
      dehydration or hypotension. In subjects with transplanted kidney, the risk of
      rejection can be enhanced either by poor compliance with immunodepressor
      treatment or by vaccination-induced antigenic stimulation. Pre-travel evaluation
      is necessary to determine metabolic, nutritional, and immune status. Subjects
      with kidney insufficiency and transplanted kidneys should be informed of the
      dangers and appropriate action in case of trouble.

PMID- 9612750
TI  - [Immunocompromised travelers].
AB  - More and more immunocompromised people travel abroad especially in tropical
      countries where infectious risks are high. Before leaving, these subjects must
      consult their general practitioner who will determine their fitness in function
      of type of immunodeficiency, travel destination, availability of medical care at
      the destination, and possibility of medical evacuation. Counseling should also be
      provided concerning the precautions necessary to avoid the hazards of exposure to
      fecal material, venereal disease, insect bites, and sun. Antimalarial drug
      prophylaxis is the same as for uncompromised subjects. Advising immunocompromised
      subjects about vaccinations is difficult since there is no consensus on the
      subject. Administration of inert vaccines is usually recommended but their
      effectiveness is often diminished and harmful effects have been observed in HIV
      infected subjects. Administration of live vaccines is always contraindicated in
      severely immunocompromised subjects but some live vaccines can be used in
      moderately immunocompromised subjects. The guidelines for vaccination differ
      depending on the underlying cause of immunodeficiency: congenital defects,
      cancer, hemopathy, treatment with immunosuppressors or corticosteroids
      (transplant patients and patients with systemic disease), HIV-infection, or
      spleen dysfunction. If there is a high risk of contracting a disease for which
      vaccination is contraindicated, drug prophylaxis or administration of
      immunoglobulins can be an alternative. If not, travel should either be postponed
      or the destination should be changed.

PMID- 9612751
TI  - [Occurrence and management of psychiatric pathology in travelers].
AB  - The relationship between mental disorders and travel are complex and multiple.
      Several clinical patterns can be distinguished. Travel is a key feature in the
      symptomatology of some psychiatric illnesses. Psychiatric manifestations can be
      induced by local living conditions in subjects with declared mental illness.
      Disorders can occur during travel in subjects with no previous history of mental
      illness. Most subjects have a previous history of mental illness prior to leaving
      France. Attending physicians should warn patients of the possible risks of
      traveling and advise them concerning prevention and management. The purpose of
      this study is to describe the relationship between travel and mental illness and
      to discuss practical measures for management and medical evacuation.

PMID- 9612752
TI  - [Cardiovascular risk for the traveler].
AB  - The incidence of cardiovascular events during travel is rising with the age of
      the population and number of traveling seniors. Cardiovascular events are the
      second most frequent reason for medical evacuation and the cause of 50% of deaths
      recorded during commercial air travel. In most cases the underlying disorder is
      coronary artery disease which is readily destabilized by stress and fatigue
      associated with travel. Inflight conditions that can cause problems include
      altitude-related hypoxia, pressurization, and cramped seating in most sections of
      the plane. Upon arrival the traveler is exposed to a variety of climatic, food,
      and environmental factors that can trigger manifestations of latent heart
      disease. Prophylactic drugs for tropical infectious disease (especially
      antimalarials of the quinidine group) should be used with caution due to possible
      adverse interaction with medications used to treat heart disease. A pre-travel
      examination is necessary to ascertain cardiovascular status and define simple
      preventive precautions.

PMID- 9612753
TI  - [Travel and chronic respiratory insufficiency].
AB  - Changes in climate, altitude and lifestyle during travel confronts patients
      presenting chronic respiratory insufficiency with special problems. A major
      challenge is related to high altitude during air travel. To limit risks, a
      preflight examination is necessary to ascertain respiratory status. Patients
      requiring oxygen therapy must ensure availability both during the flight and at
      the destination. Patients with asthma or chronic bronchitis must bring along a
      sufficient supply of usual inhalers. All patients should carry a doctor's letter
      describing their condition and listing medications. Using these elementary
      precautions, patients with chronic respiratory insufficiency can safely enjoy
      sightseeing and outdoor leisure activities.

PMID- 9612754
TI  - [Travel and patients with allergies].
AB  - By changing their surroundings and lifestyle, travelers with allergic conditions
      exposed themselves to new risks. The main perennial allergens are house dust
      mites which thrive in tropical areas and can be especially sensitizing. The risk
      of seasonal reactions to grass-pollens varies from region to region. Reactions to
      some highly sensitizing respiratory allergens can occur in travelers who return
      to regions where they were previously exposed. Subjects with food allergies
      should beware of possible reactions to ingredients in exotic dishes. The bites of
      several insects can cause anaphylactic reactions. Some medications required for
      tropical travel (e.g. antimalarial drugs) can trigger severe hypersensitivity
      reactions. Avoidance of allergens is more difficult during travel. Travelers with
      allergic conditions should carry alert identification cards and medications for
      routine as well as emergency treatment including self-injectable adrenaline.

PMID- 9612755
TI  - [First aid kits: for whom and why?].
AB  - Anyone traveling far from home should take along a first aid kit. Contents should
      be chosen carefully with the awareness that infection is not the main problem
      facing travelers. The basic kit is the same regardless of the purpose or duration
      of the trip or of the health and knowledge of the traveler. Priority should be
      given to allergic risks, to the quality of the thermometer, to the packaging of
      indispensable medications to a medical certificate justifying transport of drugs
      and syringes for personal medical use, and to preventive devices for sexually
      transmitted diseases. Travel in tropical zones raises special requirements
      especially with regard to infectious risks such as traveler's diarrhea, malaria,
      fungal and bacterial contamination. Protection against insect-borne disease and
      sun exposure are also important considerations for travel in the tropics.
      Depending on planned activities, travelers should carry medication for prevention
      and treatment of motion sickness and emergency treatment of envenimation. Due to
      local inavailabilities, it may be necessary to pack contraceptives, personal
      hygiene products, and common medications.

PMID- 9612756
TI  - [Which vaccination schedule, which vaccines? The constraints of time and age].
AB  - Several factors must be taken into account in planning vaccination schedules for
      overseas travelers. The first factor is to determine requirements mandated by
      applicable laws in the destination country and in France governing professional
      travel such as by military personnel. The other factors involve risk assessment
      including local health and epidemiological conditions, living conditions during
      the stay, and personal profile of the traveler (e.g. age and previous
      vaccination). Tropical areas are not the only destinations where infectious risks
      requiring vaccinations are found. Vaccination against diseases such as diphtheria
      and tick-borne encephalitis is necessary for several countries in Europe. Pre
      travel planning provides a timely opportunity for updating basic vaccination
      requirements (e.g. tetanus and polio). For the growing number of elderly
      travelers, accurate evaluation of immune status may be difficult either because
      these subjects may never been vaccinated but only exposed to the wild germ during
      childhood or because their vaccinations may have been performed long ago. In both
      cases one cannot be sure of the quality of the anamnestic response to booster
      injections. A frequent limitation on vaccination planning for travelers is time
      available before departure.

PMID- 9612757
TI  - [Motion sickness].
AB  - Motion sickness is a general term covering sea-sickness, car-sickness, air
      sickness, and space-sickness. Symptoms can occur when a person is exposed to
      unfamiliar movement whether real or simulated. Despite progress in the technology
      and comfort of modern transportation (planes, boats, and overland vehicles), a
      great number of travelers still experience motion sickness. Bouts are
      characterized by an initial phase of mild discomfort followed by neurologic and
      gastro-intestinal manifestations. The delay in onset depends on specific
      circumstances and individual susceptibility. Attacks are precipitated by
      conflicting sensory, visual, and vestibular signals but the underlying mechanism
      is unclear. Most medications used for prevention and treatment (e.g.
      anticholinergics and antihistamines) induce unwanted sedation. Furthermore no one
      drug is completely effective or preventive under all conditions.

PMID- 9612758
TI  - [Jet lag].
AB  - Desynchronization of circadian rhythmicity resulting from rapid travel through at
      least four time zones leads to symptoms known in everyday English as jet-lag. The
      most detrimental effect of jet-lag is fatigue with poor alertness and psychomotor
      performance. Severity is subject to individual variation in susceptibility
      (morning/evening typology, age,...) and environmental factors (direction of
      travel, number of time zones crossed, psychosocial environment...). Many measures
      used to prevent or reduce jet lag are inappropriate or ineffective and some may
      even be dangerous, such as use of melatonin. One of the most reliable preventive
      techniques consists of reinforcing social synchronizers by maintaining exposure
      to sunlight and social activity. Only two drugs currently available on the market
      can be recommended, i.e. non-benzodiazepinic hypnotics which induce high quality
      sleep to allow quick recovery and a new time-release caffeine agent which has
      been shown to prolong psychomotor performance.

PMID- 9612759
TI  - [Sun and skin and eye protection].
AB  - Overexposure to sunlight during travel can have harmful short- and long-term
      effects on the eyes and skin. Cutaneous effects include premature aging, actinic
      keratosis, and cancer. The eye is highly sensitive to invisible radiation,
      especially ultraviolet rays which can damage the crystalline lens and cornea.
      Retinal lesions usually involve the macula on which rays of the visible spectrum
      come to focus. Various natural and artificial methods can be used for sun
      protection. Limiting sun exposure is advisable for all. Sunscreens should be used
      to attenuate the effects of sun and not to prolong exposure. Fair-skinned
      subjects, especially those with numerous nevi, must use total sunscreen
      preparations starting from birth. Eye protection is necessary for everyone but
      especially young children, aphakic subjects, and patients presenting congenital
      or acquired retinal lesions. Dark lenses with a category 2 protection rating
      according to European Economic Community standards are recommended in tropical
      areas.

PMID- 9612760
TI  - [Malaria and travelers: protection and information].
AB  - With the increasing drug resistance of Plasmodium falciparum especially to agents
      used for chemoprophylaxis, every precaution must be taken to protect travelers
      from contracting malaria. Prevention of mosquito bites is a fundamental goal that
      can be achieved by a variety of means including pyrethrinoid-impregnated bed
      nets, insecticide strips, liquid vaporizers, repellents, insecticide-impregnated
      garments, and air-conditioning. There are no contraindications for vector
      control. Chemoprophylaxis depends of individual criteria as determined by
      clinical and laboratory examinations and on travel conditions (destination,
      season, duration of stay, and local living conditions). Stand-by medication
      should be prescribed for self-treatment of fever in areas where medical care is
      not readily available. Chemoprophylaxis must be continued after the traveler
      returns and medical attention should be sought if symptoms occur. To ensure
      proper compliance with preventive measures, pre-travel counseling is a mandatory
      and integral part of prevention. Information provided to travelers must be clear,
      reliable, and up-to-date.

PMID- 9612761
TI  - [Sexually transmitted diseases and travel].
AB  - Travelers are highly exposed to acquiring sexually transmitted diseases
      especially since the most popular destinations are high risk areas. While this
      risk applies to all travelers, it is highest for the "sex" tourist who is
      typically a male with a mean age of 38 years. Awareness of risks is still
      incomplete, especially with regard to HIV. Several studies have shown that only
      20% to 70% of travelers use condoms. This finding accounts for the high incidence
      of sexually transmitted diseases in returning travelers: 2% to 10%. The risk of
      HIV infection is particularly high for persons living abroad. Based on available
      data, we can define the typical profile of the high risk traveler who should be
      targeted for prevention. Prevention depends on providing adequate information
      before departure, especially concerning HIV infection. Use of a condom throughout
      sexual contact is a basic safety rule. However condom quality is poor in many
      developing countries. Returning travelers should seek medical advice if
      manifestations involving the anogenital regions should appear.

PMID- 9612762
TI  - [Individual protection against insect vectors].
AB  - Many diseases for which no vaccine is available are transmitted by insect and
      arthropod vectors, the main exceptions being yellow fever and Japanese
      encephalitis B. Treatment is less and less effective due to the development of
      chemoresistance to therapeutic and prophylactic drugs as is well-illustrated by
      malaria. One of the best methods of preventing these diseases is personal
      protection against insect bites. Personal protection measures can be divided into
      three categories which can be used separately or in combination : application of
      repellents to the skin, wearing clothes impregnated with insecticides, and use of
      bed nets and other barriers impregnated with insecticides. The choice of method
      depends on the type of insect vector involved. For insects that are active during
      the day or at dusk, application of repellents to the skin gives good short-term
      protection and wearing impregnated clothes is useful. Bed nets that have been
      properly impregnated with pyrethroids are highly effective for night-time
      protection. Since personal protection methods are not 100% effective, they must
      be used in association with chemoprophylaxis according to medical guidelines.
      Medical advice should be sought if fever should occur especially after returning
      from a trip in the tropics.

PMID- 9612763
TI  - [Viral hemorrhagic fevers: what is the risk for travelers?].
AB  - The term hemorrhagic fever covers a number of diseases with different clinical
      and epidemiologic features. All these diseases are zoonoses but their occurrence
      is not confined to tropical areas. Some occur in polar zones. Travelers to
      endemic areas for these diseases are at risk of infection. There are two modes of
      transmission. Arthropods are vectors for some diseases such as yellow fever,
      dengue fever, and Rift Valley fever which are carried by mosquitos and Congo
      Crimea virus which is carried by ticks. Airborne contamination by rodent
      excrement is responsible for transmission of hantaviruses and arenaviruses.
      Nosocomial infection is a risk for health care providers. Some types of
      hemorrhagic fever such as Bolivian hemorrhagic fever are highly localized, while
      other types such as dengue are observed worldwide. Judging from the small number
      of cases observed in European countries, the overall risk for travelers seems low
      except unless high-risk activities are planned. The main exceptions are yellow
      fever and dengue which can easily be transmitted to tourists by mosquitos. Yellow
      fever can be prevented by vaccination. Typical dengue is usually self-limited but
      hemorrhagic forms require treatment to prevent shock.

PMID- 9612764
TI  - [Non-vaccinal prophylaxis for orally transmitted diseases].
AB  - Many diseases are transmitted to man by consumption of contaminated food and
      drinking water. Orally transmitted diseases are among the main risks for
      travelers in developing and tropical countries. A variety of clinical
      manifestations can be observed but the diarrhea is the most common. In many cases
      bacterial gastroenteritis, typho-paratyphoidal fever, brucellosis, viral
      hepatitis, and various parasitic diseases can develop after various periods of
      incubation following consumption of contaminated food or drink with no initial
      reaction. Vaccination can afford protection against only few diseases. Prevention
      by applying good hygiene and common sense is the best method. By following the
      standard list of food precautions, travelers can minimize the main risks. Drug
      prophylaxis is recommended only under special circumstances. Travel medicine
      providers must have up-to-date information and possess the persuasive powers
      necessary to convince travelers to apply recommendations despite the major
      inconveniences.

PMID- 9612765
TI  - [Snakes and scorpions: what are the risks for the traveler?].
AB  - The risk of being bitten by a snake or stung by a scorpion is low for the
      ordinary, non-thrill-seeking traveler. Travelers who plan hazardous outdoor
      activities should be advised to be careful and bring along adequate protective
      clothing (boots, long trousers, and gloves). If envenomation occurs, the victim
      should be immobilized and rushed to a treatment center. Administration of
      antivenin using massive doses in severe cases is the best therapy. For quickest
      and most efficient results, antivenins should be administered by the intravenous
      route. Packing antivenins is necessary only under special circumstances when high
      risk activities are scheduled. In this case contingency planning may also be
      necessary taking into account health care facilities in the destination country
      and the availability of antivenins.

PMID- 9612766
TI  - [Road vehicle accidents during travel and their prevention].
AB  - The number of road vehicle accidents during travel outside Europe and/or under
      difficult conditions increases about 5% every year. Road accidents account for a
      third to half of medical evacuations as well as for the most serious injuries.
      The risk of accidents and their potential gravity may be enhanced by the poor
      condition of roads and vehicles. Personal factors including fatigue, speed,
      alcohol, drugs, and poor vision also play a major role. Physicians should warn
      travelers planning road trips of all these hazards and of any specific local
      conditions prevailing in certain destinations. Prevention depends on the age of
      the traveler and on any disabilities that he/she might have. Packing a first aid
      kit and inspecting safety equipment before the trip and at regular intervals
      during the trip are indispensable. Knowledge of emergency first aid procedures is
      highly recommendable. While avoiding excessiveness of any kind, the physician
      should encourage suitable psychological and material preparation in function of
      travel plans. This preparation should be aimed at reducing the risk of road
      accident particularly in developing countries. Counseling can be useful in
      reducing the risk of road accidents particularly in developing countries.

PMID- 9612767
TI  - [Migrants originally from black Africa in Marseilles and in the region of Bouches
      du-Rhone: sociological and medical aspects].

PMID- 9612768
TI  - [Marc Vaiter: the humility of a humanitarian].

PMID- 9612769
TI  - [Treatment modalities of hydatid cysts of the liver: progress or revolution?].

PMID- 9612770
TI  - [Gabon: panoply syndrome].

PMID- 9612771
TI  - [Image of the sand flea].

PMID- 9612772
TI  - [10 years of mectizan donation].

PMID- 9612773
TI  - [The expansion of tropical diseases; inevitability or human factors?].

PMID- 9612774
TI  - [Overproduction of tumor necrosis factor-alpha in African patients with HIV-1
      infection, cachexia and low tri-iodothyronine syndrome].
AB  - Sick euthyroid syndrome characterized by low triiodothyronine (T3) levels is
      observed in advance stages of HIV infection. The purpose of this prospective
      study was to determine if proinflammatory cytokines play and role in the
      pathogenesis of this syndrome in HIV-1-infected patients. Serum levels of tumor
      necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1 beta were measured in 40
      African patients presenting HIV-1 infection associated with low T3 levels in 20
      cases (group I) and normal or elevated T3 levels in 20 cases (group II).
      Elevation of serum TNF-alpha levels was more common and mean serum TNF-alpha
      level was significantly higher in group I than group II (116 +/- 39 versus 3.05
      +/- 0.04 pg/ml; p < 0.01). Serum IL-1 beta levels were not significantly
      different between the two groups. These findings are consistent with previous
      experimental data and suggest that sick euthyroid syndrome in cachectic HIV-1
      infected patients may be due to overproduction of TNF-alpha.

PMID- 9612775
TI  - [Serum HRP-2 antigens and imported Plasmodium falciparum malaria: comparison of
      ParaSight-F and ICT malaria P.f].
AB  - Serum levels of HRP-2 antigens against Plasmodium falciparum in 568 venous blood
      samples collected at two general hospitals were evaluated using the ParaSight-F
      (Becton-Dickinson) alone (568/568 samples) or in combination (156/568 samples)
      with the new ICT-Malaria P.f. (ICT-diagnostic). Comparison with the reference
      method (thin and thick blood smears assessed by two experienced parasitologists)
      showed that both tests were highly sensitive (93% and 96% respectively) and
      specific (98% and 98% respectively). The positive predictive values of the two
      tests were equal (96%) and the negative predicative values were close (96% and
      98% respectively). Although both tests provided results within 10 minutes and
      required no special equipment for interpretation, the ICT-Malaria P.f. test
      seemed simpler and easier to use than the ParaSight-F test. The ParaSight-F test
      alone was used to monitor serum antigen levels after treatment in 24 patients.
      Antigen levels remained positive for at least three days after disappearance of
      circulating parasites (range: 3 to 28 days). Evaluation of serum levels of HRP-2
      antigens can be useful for emergency diagnosis, especially in patients with low
      circulating parasite levels. The ICT-Malaria P.f. test seems especially suited
      for in-field use.

PMID- 9612776
TI  - [Surveillance of the in vivo sensitivity of Plasmodium falciparum to antimalarial
      agents: the results of initial tests of the OCEAC Malaria Network].
AB  - The Malaria Control Division of the Organization for Endemic Disease Control in
      Central Africa (OCEAC) has developed a standardized method to measure the in vivo
      sensitivity of Plasmodium falciparum to antimalarial drugs. Between May 1996 and
      February 1997, a first series of tests using this method was carried out to
      determine the sensitivity of Plasmodium falciparum to chloroquine and amodiaquine
      in infected school children in four capital cities: Yaounde, Brazzaville, Malabo,
      and Libreville. As expected, only children presenting more than 100 parasites per
      1000 leucocytes were enrolled. Results showed variable degrees of in vivo
      resistance to chloroquine and amodiaquine at each location: 25% and 13%
      respectively in Yaounde, 19% and 11% in Malabo, 23% and 43% in Brazzaville, and
      29% and 0% in Libreville. Overall results concerning chloroquine of this test
      series were similar to recent data in comparable populations and confirmed the
      idea that the situation has stabilized in Central Africa. Findings concerning
      amodiaquine raise the need for further study to validate and explain the
      contrasting findings in Libreville (0%) and Brazzaville (43%). This first
      experience shows that the method is simple and quick and that it can be used with
      minimal means. Results could provide important early warning data for national
      health officials.

PMID- 9612777
TI  - [Infectious etiology of diarrheal morbidity in a Senegalese region of high
      exposure to Schistosoma mansoni].
AB  - Endemic schistosomiasis due to Schistosoma mansoni has been observed in Richard
      Toll (The Senegal River basin) in Senegal since 1990. Because of its high
      prevalence, schistosomiasis is assumed to be the cause of most cases of diarrhea
      observed in the region. The purpose of the present study carried out within the
      framework of the ESPOIR program for control of bilharziasis in the Senegal River
      region was to confirm the exact etiology of diarrhea in the region. A total of
      109 subjects presenting diarrhea including 57 children under the age of 5 years
      were included in the study. In all cases, stool examination using appropriate
      techniques was performed to detect bacterial, viral, and parasitic agents.
      Schistosoma mansoni was identified in 47 cases (43.1%). Stool cultures were
      positive in 28 cases (25.6%) for Escherichia coli (n = 9), Shigella spp. (n =
      18), and Salmonella spp. (n = 1). With regard to Shigella, a predominance of the
      Shigella dysenteriae type I stereotype (10/18) and a high incidence of co
      infection involving Shigella spp. and Schistosoma was noted. Rotavirus infection
      was observed in 6 cases involving subjects under the age of 5 years. The relative
      incidence of the different infectious agents varied widely in function of age.
      This study in an endemic area of bilharziasis in Senegal demonstrates that
      Schistosoma mansoni should not be assumed to account for all cases of diarrhea
      occurring in the area.

PMID- 9612778
TI  - [Epidemiologic aspects of 42 cases of human brucellosis in the Republic of
      Djibouti].
AB  - Brucellosis is an ubiquitous anthropozoonoses in the Republic of Djibouti, but it
      has only been studied in the City of Djibouti. This retrospective study of 42
      cases of human brucellosis diagnosed between April 1993 and April 1995 was
      carried out at the Peltier Hospital in Djibouti to obtain epidemiological data
      concerning brucellosis in the Republic of Djibouti. Diagnosis was based on
      clinical symptoms and positive immunologic tests (Rose Bengal test > 100 UI and
      Wright serology > 1/80). The following information was obtained for each patient:
      nationality, ethnic origin, place of residence, age, sex, and risk factors for
      exposure to infected animals or products. There were 30 men and 12 women
      including 38 Djiboutis, 3 Somalis, and 1 Ethiopian. Ethnic origin was Afar in 32
      cases, Somali in 6 cases, and undetermined in 4 cases. Mean age was 31.6 years.
      Of the 38 Djiboutis, 15 lived in the district of Djibouti, 17 in the district of
      Tadjourah, 3 in the district of Obock, and none in districts located in the
      Southern part of the country. In 18 cases brucellosis involved cattle raisers
      from the Northern part of the country. In five cases no risk factor could be
      identified. The incidence of brucellosis in the Republic of Djibouti appears to
      be comparable to that observed in other highly endemic countries. Further study
      is needed to determine the exact incidence in man and animals and ascertain the
      need and feasibility of preventive measures.

PMID- 9612779
TI  - [The distribution of freshwater molluscs the intermediate hosts of human
      schistosomas in Katan, south-Kivu].
AB  - In eastern Democratic Republic of Congo, the prevalence of bilharziasis due to
      Schistosoma mansoni is high along the Kivu lake shoreline where Biomphalaria
      pfeifferi, i.e. the intermediate host of Schistosoma mansoni, is the only snail
      that has been described until now. Although their occurrence has not been
      reported in the area, other schistosomas remain possible since their intermediate
      hosts are present. This study was carried out in 1992 to determine the
      distribution of intermediate host snails in freshwater systems in the region.
      Samples were collected according to the standardized harvest time unit method.
      Five species of intermediate host snails for human schistosomiasis were
      identified. By far the most prevalent species was Biomphalaria pfeifferi which
      was found in 75% of the freshwater systems studied. Given the presence of
      Schistosoma mansoni in the region, spread of this type of schistosome is likely.
      Ferrissia burnipi, the recognized intermediate host of Schistosoma haematobium,
      was observed in association with Biomphalaria pfeifferi. Snails of the Bulinus
      genus were confined to special environments. Factors preventing infestation by
      Schistosoma haematobium and Schistosoma intercalatum remain unclear. Control
      measures against snails and their larvae in fresh water systems in the region are
      needed to stop the spread of Schistosoma mansoni and prevent the appearance of
      Schistosoma haematobium and Schistosoma intercalutum.

PMID- 9612780
TI  - [Multiple organ failure syndrome after ovarian hyperstimulation].
AB  - Ovarian stimulation is used to treat female infertility, especially in Black
      Africa where infertility is considered as shameful. Ovarian stimulation can lead
      not only to multiple pregnancies but also to severe systemic complications such
      as the one described in this report. Ovarian stimulation using human menopausal
      gonadotropin led to ovarian hyperstimulation and multiple organ failure in a 28
      year-old Senegalese woman. Symptomatic treatment using corticosteroids, abdominal
      paracentesis to relieve ascites, and fluid expansion failed. Bilateral
      ovariectomy was performed resulting in permanent sterility. Ovarian stimulation
      requires close monitoring by ultrasound visualization and measurement of 17 beta
      estradiol to allow early detection of complications.

PMID- 9612781
TI  - [The drug trade between European countries and developing countries].
AB  - The quality of medicinal products marketed in developing countries has recently
      become the focus of lively debate and new interest. This report describes a
      survey conducted among officials from exporting and importing countries designed
      to evaluate the content and enforcement of current regulations. Resulting data
      indicated that, despite the high volume of trading in medicinal products between
      European and developing countries, regulations are poorly applied and many
      infractions occur. The most obvious abnormalities involve definition of market
      status. A list of banned is issued by the WHO but not by the European Economic
      Community. Regulations regarding generic products differ from one country to
      another and, since determination of the exact origin of a product may be
      difficult, compliance with good manufacturing practices is often unverifiable. A
      more cooperative attitude on the part of exporting countries and standardization
      of formalities on the part of importing countries will be necessary to stem the
      growing tendency to consider medicinal products as ordinary goods.

PMID- 9612782
TI  - [Obesity and developing countries of the south].
AB  - An adult is considered as overweight if his body mass index is 25.0 kg/m2 or more
      and as obese if it is 30.0 kg/m2 or more. Since excess weight is a predisposing
      factor for many chronic diseases, e.g. diabetes, an increase in its incidence in
      the population is cause for concern. Until now, excess weight has been problem of
      epidemic proportions only in developed countries, but it has recently spread to
      the developing world. More than 30% of the population in Latin America, the
      Caribbean, the Middle East, and Northern Africa is overweight. Populations living
      on Pacific and Indian Ocean islands have the highest prevalence of obesity in the
      world. In Asia and Black Africa, the overall prevalence of overweight is still
      low but incidence is high in urban areas. In most of these countries, both
      underweight and overweight people can now be seen. In many countries, the
      increase in the number of overweight people has occurred within the last few
      years. Excess weight appears first among the affluent and then among low-income
      classes including young children and teenagers. The main causes are a nutrition
      transition to lipid-rich diets and, above all, reduced physical activity in city
      dwellers. Obesity and associated diseases could become major problems in the
      future since malnutrition during fetal development and early childhood are
      predisposing factors. Already overweight is creating an extra burden for
      countries where malnutrition and nutritional deficiencies are still observed in
      young children. Given the economic costs of management of obesity-related
      diseases, surveillance and prevention programs are needed to stem the growth of
      this problem.

PMID- 9612783
TI  - [Human onchocerciasis in Africa].
AB  - Before the 1980s, the only available method for control of onchocerciasis was
      elimination of blackfly vector populations. This strategy was used with
      considerable success in the Onchocerciasis Control Programme in West Africa
      (OCP). The discovery of ivermectin, the first effective drug suitable for mass
      treatment of onchocerciasis, has revived international interest not only in
      fundamental research but also in development of new strategies to control
      onchocerciasis in the countries outside the OCP area. This report gives an
      overview of current parasitological, clinical, epidemiological and diagnostic
      data about onchocerciasis. Although little is known about the early development
      of Onchocerca volvulus in the human host, significant insight has been gained
      into the population dynamics of the parasite. The pathogenesis of cutaneous and
      ocular manifestations in onchocerciasis is now better understood. Epidemiological
      studies are under way to evaluate the extent of systemic manifestations. Recently
      developed diagnostic methods are more sensitive than conventional parasitological
      techniques. A new method for rapid assessment of endemic level has provided a
      detailed picture of the distribution of onchocerciasis. Species- and strain
      specific DNA probes have been developed for identification of parasites in West
      Africa. New methods for quantifying disability allow evaluation of the socio
      economic impact of the cutaneous and ocular complications of onchocerciasis.

PMID- 9612784
TI  - [Malaria, anopheles, the anti-malaria campaign in French Guyana: between
      dogmatism and judgment].
AB  - The recrudescence of malaria in French Guiana involves both border regions. One
      notes the predominance of Plasmodium falciparum along the Maroni River on the
      Surinam frontier and the transmission of both Plasmodium falciparum and
      Plasmodium vivax in amerindian settlements along the Oyapock River on the
      Brazilian frontier. The main mosquito vector is the endoexophile species,
      Anopheles darlingi. The role of man-biting forest anophelines in malaria
      transmission is still unclear. At the present time, malaria control is based on
      curative treatment of the confirmed cases (approximately 4,000 cases a year by
      active and passive screening). Vector control is supported by annual houses
      insecticides spraying and, to a lesser degree, use of insecticide-impregnated
      bednets. The main limiting factors for successful control have been difficulty in
      implementing a strategy adapted to the cultures of the amerindian and bushnegro
      populations living on either side of the river-frontiers and in organizing
      effective cross-border cooperation. The alleged role of immigration in
      transmission dynamics has been more speculative than real. However the growth of
      the population and the increase of human activities inside rain forest areas have
      favorized Anopheles darlingi breeding by uncontrolled deforestation. This
      situation need to be monitored closely. Information campaigns to improve public
      awareness could be useful. Following measures could improve control in sparsely
      populated, remote areas: to promote an integrated preventive program for a real
      community-wide distribution of primary health care; to discontinue insecticides
      spraying in houses which is poorly accepted by the bushnegro population and
      unsuitable to the amerindian dwellings; to support the use of personal
      protection; to initiate an effective anopheline larvae control; to determine the
      impact of the transmission during day-time activities especially among very small
      settlements far from the main villages where members of the Djuka tribe practise
      slash-and-burn cultivation. Teledetection might be highly useful for monitoring
      the epidemiology of malaria in French Guiana and neighbouring countries. A change
      in the official administrative dogma and policy is necessary to optimize malaria
      control within the framework of regional cooperation between Brazil and the three
      Guianas.

PMID- 9612785
TI  - [Epilepsy and its impact in northwest region of the Central African Republic].
AB  - In African countries, epilepsy is an important public health problem with major
      medical, socio-cultural, and economic implications. This study was carried out to
      evaluate attitudes towards epilepsy in the Central African Republic. A total of
      187 epileptic patients were included. Only 20.9% of the study population were
      married. School attendance never exceeded the elementary level. Epilepsy was
      active in 98.4% of patients who continued to present attacks despite extensive
      treatment which was either poorly complied with or inadequate. Attitudes towards
      epilepsy remain rooted in belief in supernatural phenomenon and evil spirits with
      use of traditional therapies involving abstinence from certain foods and use of
      laxative agents to drive out evil forces. Epileptics are excluded from their
      families and not allowed to attend school but, in our study, they were not
      prevented from the work place since 70% held jobs. In this study, 54% of
      epileptics believed that the disease was contagious, 55.6% that it was incurable,
      and 20.9% that it was due occult or supernatural causes. While precise
      quantification is impossible, our experience based on interviews with patients
      and frequent observation of burn wounds suggests that moral and physical
      suffering is immense among epileptics in the Central African Republic. Epilepsy
      in Black Africa is a major public health problem requiring serious attention from
      government officials, health care specialists, and the families of patients.
      Better information to promote awareness of the non-contagious nature of the
      disease, greater support for families of patients, and improvement in treatment
      compliance are essential.

PMID- 9612786
TI  - [The adaptation of therapeutic standards as a function of antibiotic sensitivity
      of strains of Shigella spp. isolated in Rwanda in 1997].

PMID- 9612787
TI  - [2 murine angiostrongyliasis in the Caribbean and their human consequences: a
      menace for Haiti?].

PMID- 9612788
TI  - [Plasmodium falciparum malaria and negative HRP2 results: an explanation?].

PMID- 9612789
TI  - [Exophiala jeanselmei pheohyphomycosis in a Senegalese patient with HTLV-I
      infection and lymphoma].

PMID- 9612790
TI  - [Maxillofacial location of Burkitt lymphoma at the University Hospital Center of
      Ouagadougou, Burkina Faso].

PMID- 9612791
TI  - An ischaemic switch for gene therapy vectors.

PMID- 9612792
TI  - Lupus: complement cascade, Fc receptors ... or both?

PMID- 9612793
TI  - Diagnosing weight disorders by measuring uncoupling proteins.

PMID- 9612794
TI  - Molecular handles open the door to novel biomaterials and cancer therapies.

PMID- 9612795
TI  - The new cardiology. The American College of Cardiology 47th Annual Scientific
      Session. Atlanta, GA, USA, 29 March-1 April 1998.

PMID- 9612796
TI  - Getting to the heart of gap junction pathology. Novartis Foundations Symposium:
      Gap junction-mediated intercellular signalling in health and disease. London, UK,
      3-5 March 1998.

PMID- 9612797
TI  - Therapeutic approaches for sticky situations. IBC Conference on Integrins:
      applying multidisciplinary approaches for targeted therapies. Cambridge, MA, USA,
      29-30 January 1998.

PMID- 9612799
TI  - Fanconi's anemia: what have we learned from the genes so far?
AB  - Fanconi's anemia (FA) is a rare genetic disorder affecting children at an early
      age; patients suffer from progressive bone marrow failure and, in many cases,
      from congenital malformations. As cells from FA patients have an increased
      sensitivity to DNA-crosslinking agents, FA has been included among the group of
      DNA repair disorders. However, identification of a specific DNA repair defect in
      FA has not been firmly established. None the less, this cellular phenotype has
      allowed the classification of FA patients into eight complementation groups
      defining eight possible FA genes. Two of these genes have now been cloned and,
      although they have raised more questions than they have answered, are
      facilitating the identification of cellular processes implicated in the
      pathophysiology of FA, and the design of new therapies.

PMID- 9612798
TI  - Do endogenous cannabinoids contribute to HIV-mediated immune failure?
AB  - The failure of the immune system to mount a successful attack on the human
      immunodeficiency virus (HIV) is an old enigma for AIDS research. The high
      mutational capacity of HIV, which unremittingly confuses the immune system, is a
      major factor in immune failure. But this alone cannot fully explain the certain
      and inescapable failure of the immune system, leading to full-blown AIDS. Here,
      we propose the hypothesis that endogenous cannabinoids, derived mostly from
      macrophages, might participate in the general failure of the immune system in HIV
      infected individuals.

PMID- 9612800
TI  - Advances in the diagnosis of infection in prosthetic joint implants.
AB  - The widespread use and dramatic success of prosthetic joint implant surgery
      (arthroplasty) has greatly improved the quality of life for many individuals
      suffering from degenerative, arthritic, or injured joints. However, in a number
      of cases, recipients experience discomfort at the arthroplasty site that can
      signal biomechanical failure, or periprosthetic infection of the joint, or both.
      In fact, infection remains a devastating obstacle, preventing arthroplasty from
      being an almost perfect medical procedure. Existing tests for the diagnosis of
      infection in orthopedics are disappointing because of the relatively high
      frequency of false negative results. To overcome this shortcoming, and to reduce
      the number of infected revision arthroplasties, a methodology based on molecular
      biology has been established. The method allows the rapid, sensitive and accurate
      diagnosis of orthopedic infections, and should aid the clinician with treatment
      regimens, surgical decisions, and overall patient management in the growing
      arthroplasty population.

PMID- 9612801
TI  - Muscle maturation: implications for gene therapy.
AB  - Skeletal muscle is a promising target tissue for gene therapy, for both muscle
      and non-muscle disorders. A variety of methods have been studied to transfer
      genes into skeletal muscle, including retroviral, adenoviral and herpes simplex
      viral vectors. However, various factors impede muscle-based viral gene therapy.
      Here, we discuss why some viral vectors cannot efficiently transduce mature
      muscle fibers, and describe some new approaches to overcome this barrier.

PMID- 9612802
TI  - Therapeutic uses of microencapsulated genetically engineered cells.
AB  - Microencapsulated genetically engineered cells have the potential to treat a wide
      range of diseases. For example, in experimental animals, implanted
      microencapsulated cells have been used to secrete growth hormone to treat
      dwarfism, neurotrophic factors for amyotrophic lateral sclerosis, beta-endorphin
      to decrease pain, factor XI for hemophilia B, and nerve growth factors to protect
      axotomized neurons. For some applications, microencapsulated cells can even be
      given orally. They can be engineered to remove unwanted molecules from the body
      as they travel through the intestine, and are finally excreted in the stool
      without being retained in the body. This application has enormous potential for
      the removal of urea in kidney failure, ammonia in liver failure and amino acids
      such as phenylalanine in phenylketonuria and other inborn errors of metabolism.

PMID- 9612803
TI  - Changes in astigmatism after ptosis surgery measured by corneal topography.
AB  - A computerized topographic analysis system (EyeSys [EyeSys Technologies, Houston,
      TX, U.S.A.]) was used to evaluate corneal astigmatic changes (central corneal
      power and astigmatic axis) after blepharoptosis surgery on 29 eyelids (22
      patients). Fifteen nonoperated eyelids of study patients undergoing unilateral
      ptosis repair were used as controls. All patients were evaluated preoperatively
      and again 6 weeks after surgery. Fifteen operated eyelids and five controls were
      also examined 12 months after surgery to evaluate the stability of these
      measurements. In 72.4% of operated eyes, corneal topography demonstrated
      increased with-the-rule astigmatism 6 weeks after surgery, 13.8% of surgical eyes
      showed increasing against-the-rule astigmatism, and in 13.8%, no change was noted
      from preoperative measurements. None of the 15 control eyes demonstrated any
      change in corneal astigmatic axis or significant change in central corneal power.
      By 12 months after surgery, all of the operated eyes showed a regression toward
      the amount and pattern of preoperative astigmatism. Only two of 15 eyes
      maintained a difference of > 0.3 D of central corneal power greater than their
      preoperative measurement at 1 year. These data suggest that corneal topography
      may be altered by changes in eyelid position, although the changes appear to be
      temporary in most patients.

PMID- 9612804
TI  - Long-term results of frontalis suspension using irradiated, banked fascia lata.
AB  - This study was undertaken to study the long-term rate of recurrence of ptosis and
      other postoperative complications after frontalis suspension using banked
      irradiated fascia lata. One hundred thirty-two lids of 72 patients underwent
      frontalis suspension between 1980 and 1989. The preoperative diagnoses included
      severe congenital ptosis (83%), blepharophimosis (10%), third nerve palsy (4%),
      and chronic progressive external ophthalmoplegia (3%). The age at the time of
      surgery ranged from 5 months to 19 years, with an average of 3 years and 5
      months. In 46 patients (64%), surgery was done before age 3 years. The follow-up
      time ranged from 6 to 15 years, with a mean and median of 10 years. Good to
      excellent lid height was achieved immediately after surgery in all but three
      patients. Recurrence of ptosis occurred in 20 cases (28%), and 28 lids (21%). The
      time to reoperation ranged from 1 to 7 years, with an average of 3 years. Sixteen
      patients (80%) with recurrence were younger than 3 years of age. Reaction to
      donor fascia lata occurred in only two patients (3%). Only one patient suffered
      from excessive exposure keratopathy and required revision of the sling. Banked
      fascia lata is easy to use and should be considered as an alternative suspensory
      material in children younger than 3 years of age with congenital ptosis. The long
      term reoperation rate in this cohort of patients was higher than the 5% rate
      reported for autogenous fascia, but lower than that previously reported for
      banked fascia lata (50% at 8 years).

PMID- 9612805
TI  - The role of proliferating cell nuclear antigen (PCNA) in predicting biologic
      behavior of lymphoid infiltrates of the orbit and ocular adnexae.
AB  - The authors performed a retrospective clinicopathologic review of lymphoid tumors
      of the orbit and ocular adnexa. In addition, we used an immunohistologic marker
      for proliferating cell nuclear antigen (PCNA), an intranuclear protein with
      greatest expression in actively proliferating (dividing) cells, to determine
      whether levels of PCNA can be correlated with the presence or future development
      of systemic lymphoma. To the authors' knowledge, the present study represents the
      first in which PCNA indices, i.e., the number of cells that showed diffuse
      intranuclear staining for PCNA averaged per 10 high power field (HPF), were
      correlated with systemic disease in orbital and ocular adnexal lymphomas. The
      percentage of B- and T-cells in the tumor infiltrate was also determined.
      Followup data showed that two patients with eyelid involvement had preexisting
      systemic lymphoma, whereas another with bilateral lacrimal gland disease later
      developed systemic lymphoma. Followup times ranged from 24 to 42 months (mean
      39.7 months). The mean PCNA level in three patients with systemic disease was
      13.3 and in the six patients with no systemic disease was 33.8. These results
      suggest that PCNA alone cannot be used as a marker for the presence of, or
      development into, systemic lymphoma.

PMID- 9612806
TI  - Nodular sclerosing Hodgkin disease with primary manifestation in the orbit.
AB  - Hodgkin disease with primary manifestation in the orbit is extremely rare, and
      even when suspected can be very difficult to diagnose. Its clinical and
      histological presentation can be nearly impossible to differentiate from that of
      a benign inflammatory process, and it is necessary to utilize immunohistochemical
      techniques to confirm the diagnosis. This article focuses on a case of nodular
      sclerosing Hodgkin disease with initial manifestation in the orbit. A comparison
      of the clinical, histological, and immunohistochemical presentations associated
      with both Hodgkin disease and benign inflammation is discussed. A brief review of
      the immunohistochemistry specific for Hodgkin disease is also provided.

PMID- 9612807
TI  - Spindle-cell lipoma of the preseptal eyelid.
AB  - An 82-year-old woman had experienced progressive enlargement of a long-standing
      left upper lid mass for 3 weeks. The superior visual field was compromised
      secondary to mechanical ptosis from this lid lesion. Computed tomography showed a
      large lid mass with a low density signal, similar to intraorbital fat. The tumor
      was completely excised. Histopathologic examination showed an encapsulated tumor
      composed of mature adipose tissue interspersed with fibrovascular septa
      containing spindle-cells, confirming a diagnosis of spindle-cell lipoma.

PMID- 9612808
TI  - Sino-orbital giant cell reparative granuloma.
AB  - An otherwise healthy, 9-year-old boy had gradual onset of a mass deformity in the
      region of the left medial canthus with resulting superior and lateral globe
      displacement. Radiographic evaluation demonstrated an osteolytic, expansile
      lesion involving the bones of the ethmoid and maxillary sinuses. Combined
      anterior orbitotomy and nasal endoscopic surgical resection revealed additional
      involvement of the nasolacrimal sac wall. Histopathology was consistent with a
      giant cell reparative granuloma. The authors know of 15 case reports of sino
      orbital giant cell reparative granulomas with ophthalmic manifestations; only 3
      of these appeared in the ophthalmology literature. This case appears unique in
      that extension of the abnormal tissue into the nasolacrimal sac wall was
      demonstrated.

PMID- 9612810
TI  - Subperiosteal hematoma of the orbit: case presentation.
AB  - A 14-year-old boy was referred with complaints of decreased vision, pain, and
      diplopia that developed in his right eye after trauma. Radiologic studies showed
      an orbital roof fracture with an associated subperiosteal hematoma. Orbital
      exploration with surgical drainage of the hematoma and roof fracture repair was
      performed. Postoperatively, he experienced complete visual recovery with
      resolution of his proptosis and diplopia. Subperiosteal hematomas of the orbit
      should be considered in the differential diagnosis of acute unilateral proptosis
      after trauma. The authors suggest that early intervention results in rapid
      patient recovery.

PMID- 9612809
TI  - Silicon granulomas and dermatomyositis-like changes associated with chronic
      eyelid edema after silicone breast implant.
AB  - Silicone medical products may be associated with various complications. Recent
      attention has focused particularly on health risks associated with silicone
      breast implants. The authors present the clinical and histopathological findings
      in a 71-year-old woman who had previously undergone breast reconstruction with a
      silicone gel-filled elastomer envelope-type breast implant and who developed
      severe chronic eyelid edema and inflammation. Extensive systemic evaluation and
      serologic studies were unrevealing, prompting biopsy of the eyelids.
      Histopathologic evaluation of the upper eyelids revealed scattered noncaseating
      granulomas throughout the dermis, an atrophying interface dermatitis with a
      sparse perivascular lymphocytic infiltrate, and focal perivascular and
      interstitial lymphocytic infiltrates of the muscles. Scanning electron microscopy
      demonstrated particles of material within the granulomas, which were revealed by
      electron probe x-ray microanalysis to contain silicon. The presence of silicon
      containing material within areas of eyelid inflammation supports a role for
      silicon in the pathogenesis of this patient's condition. In the absence of other
      predisposing conditions, migration of silicone breast implant material must be
      considered.

PMID- 9612811
TI  - Anterior orbital varix presenting as a lacrimal sac mucocele.
AB  - A 35-year-old woman was referred to the Oculoplastics Clinic because of a left
      nasal swelling and intermittent tearing of 1 year's duration. The clinical
      examination and echographic and radiologic findings were consistent with an
      anterior venous anomaly. Complete surgical excision was performed and
      histopathology confirmed the diagnosis of a varix.

PMID- 9612812
TI  - Use of temporalis fascia for exposed hydroxyapatite orbital implants.
AB  - The hydroxyapatite implant (Bio-Eye, Intergrated Orbital Implant, Inc., San
      Diego, CA, U.S.A.) has gained increasing popularity as an orbital implant in
      recent years. Several complications may occur, including infection, exposure,
      extrusion, and various peg problems. Exposure of the implant appears to be the
      most common complication, ranging up to 21.6%. Many techniques, including
      nonsurgical and surgical approaches, have been described to manage these
      exposures. When surgery is indicated, a patch graft may be required to cover the
      defect. We report our experience and technique with autogenous temporalis fascia
      as a patch graft. Autografts such as temporalis fascia are easily obtained, bring
      about no immunological reaction, and have no risk of infectious transmission.

PMID- 9612813
TI  - The Muller muscle flap for repair of an exposed hydroxyapatite orbital implant.
AB  - A 36-year-old woman was experiencing discomfort and discharge after placement of
      an orbital implant 1 year previously. Her ocular history included iridocorneal
      endothelial syndrome, requiring two trabeculectomies, the last of which included
      the use of 5-fluorouracil (5-FU). After enucleation, a hydroxyapatite orbital
      implant was placed. Shortly thereafter, an implant exposure developed and
      continued to enlarge to 11 mm even after her ocularist had elevated the
      prosthesis off the exposed area and surrounding conjunctiva. Magnetic resonance
      imaging with gadolinium enhancement was not obtained because of the prohibitive
      cost. Fourteen months later, a vascularized Muller muscle pedicle flap was
      devised and tunneled underneath the existing conjunctiva to cover the defect. The
      overlying levator was undisturbed; however, transient ptosis occurred that
      returned to baseline after 2 weeks. This is a new and novel approach to restore
      orbital implant exposure and may be most helpful after antimetabolite treatment
      to the conjunctiva or radiation to the orbit.

PMID- 9612814
TI  - Surgical management of circumscribed conjunctival melanomas.
AB  - Circumscribed conjunctival melanoma usually arises in the bulbar conjunctiva and
      less often in the forniceal or palpebral conjunctiva. After simple superficial
      removal, employed by many ophthalmologists, these tumors have an increased
      tendency toward local recurrence and distant metastasis. A surgical procedure
      designed to remove the tumors completely and minimize the changes of recurrence
      would be desirable. The authors employed a surgical approach to conjunctival
      melanoma excision, which they believe insures more complete tumor removal and
      decreases the chances of recurrence and metastasis. The surgical management of
      melanoma in the limbal region of the bulbar conjunctiva consists of localized
      alcohol epitheliectomy, removal of the mass by a partial lamellar
      scleroconjunctivectomy, and supplemental double freeze-thaw cryotherapy to the
      adjacent remaining conjunctiva by a specific technique. For tumors located in the
      forniceal or palpebral conjunctiva, wide surgical resection with alcohol
      treatment to the scleral base and cryotherapy to the surrounding conjunctiva is
      performed. A "no touch" technique is employed and direct manipulation of the
      tumor is strictly avoided in an effort to prevent tumor cell seeding into a new
      area. The technique currently employed has evolved from experience with
      circumscribed conjunctival melanoma excision during a 20-year period. About 80
      patients had circumscribed conjunctival melanoma unassociated with appreciable
      primary acquired melanosis. Although it is not the purpose of this article on
      surgical technique to provided a detailed statistical analysis of the results,
      the authors currently believe that this technique should be employed in all cases
      of circumscribed lesions in which conjunctival melanoma is a diagnostic
      consideration. Incisional biopsy and frozen sections are generally not advisable.
      Preliminary observations suggest that this method decreases the chances of local
      recurrence.

PMID- 9612815
TI  - Mixed type basal cell carcinoma of the eyelids.
AB  - A retrospective histopathologic review of 97 patients with basal cell carcinoma
      of the eyelid was performed to determine the prevalence and behavior of tumors
      with a mixed pattern of growth. A mixed type basal cell carcinoma was defined as
      a tumor having a significant nodular or ulcerative component combined with an
      infiltrative component. Histologic classification of the 97 tumors yielded four
      (4.1%) that were multicentric, 67 (69.1%) that were nodular, one (1%) that was
      ulcerative, 13 (13.4%) that were infiltrative, and 12 (12.4%) that were the mixed
      variant. Follow-up was obtained on 8 of the 12 patients with mixed basal cell
      carcinoma. Three tumors recurred, but there were no tumor-related deaths. One of
      these patients underwent numerous eyelid resections over a 2-year period and then
      underwent an orbital exenteration. The authors conclude that mixed type basal
      cell carcinomas are not infrequent and behave as aggressively as basal cell
      carcinomas of the morphea type. A greater awareness and recognition of mixed type
      basal cell carcinomas by ophthalmologists and pathologists should result in fewer
      recurrences and better patient management.

PMID- 9612816
TI  - The arrowhead skin-muscle flap in the closure of lower eyelid defects.
AB  - Lower-lid defects can arise from many sources, but they are often the result of
      excision of lower-lid tumors. The excision of the lesion is often performed by
      means of a pentagonal wedge resection. After repair of the tarsus and
      reapproximation of the lid margin, the skin and orbicularis are usually closed in
      a vertical fashion, which is perpendicular to relaxed skin tension lines and may
      extend further down the lid than is optimal as a result of a dog-ear excision.
      The authors propose a new method for closure of skin and orbicularis muscle in
      repair of lower eyelid marginal defects. This method is simple and has several
      advantages over vertical closure: it follows relaxed skin tension lines, allows
      closure of the anterior lamella in the opposite direction from the posterior
      lamella, and leaves an infraciliary scar rather than a vertical scar extending
      down the cheek. This method has been used in over 100 patients during the past 8
      years, and no significant complications have occurred. Potential disadvantages of
      the technique include increased vertical tension and a tendency for the lid to be
      pulled downward. For these reasons, the arrow-head flap would not be the best
      choice in patients with preexisting lower eyelid retraction, cicatricial
      ectropion, or vertically tight lower-lid skin.

PMID- 9612817
TI  - [Parasitism--the existence of organisms as a component of parasitic systems].
AB  - Attempt to give a definition of the parasitism phenomenon from the
      symbiotological point of view is proposed. Parasites are the organisms, existence
      of which is possible only in the parasitic systems of any degree of complexity.
      Outside the parasitic system the parasite is not capable to realize its main
      vital function including feeding, dispersion of reproduction. The parasitism as
      the biological phenomenon could be defined as the existence of organisms in the
      structure of parasitic systems.

PMID- 9612818
TI  - [The relationship of the larval behavioral traits of the malarial mosquito
      Anopheles messeae (Diptera: Culicidae) to its sensitivity to the entomopathogenic
      bacterium Bacillus thuringiensis subspecies israelensis].
AB  - Behavioural actions of the malarial mosquito Anopheles messeae larvae and their
      correlations with the susceptibility to the entomopathogenic bacterium Bacillus
      thuringiensis israelensis (Bti) were studied. The larvae were differentiated
      according to their feeding mode ("filter-feeders" and "scraper-feeders") and to
      their avoidance reaction on a concussion of water surface by water drops
      ("divers" and "undivers"). The "scraper-feeders" and "divers" showed a tendency
      of decreased susceptibility to Bti, while the "filter-feeders" and "undivers" did
      not. The presence of the white pigment (striped genotypes) on a dorsum of the
      larvae correlated with the reaction of avoidance and phyllotaxis but not with the
      susceptibility to Bti.

PMID- 9612819
TI  - [Cyclic processes in the dynamics of the population count of the taiga tick and
      their relation to weather and climatic conditions].
AB  - The paper continues the discussion of published materials on the dynamic of
      Ixodes persulcatus number in mountain forests of the central part of the
      Krasnoyarsk region during 1958-1990 (Korotkov e. a., 1992). An unstationarity and
      polycyclicity of examined processus is confirmed. It is shown, that long-term and
      middle-term quasi-periodical fluctuations of the tick number are determined by
      successive changing in forest biocenoses going under the influence of respective
      fluctuations of the climate. The synchronization of climatic and biocenotic
      processes is complicatedly organized in time and is not indicated
      phenomenologically. Certain quasi-periodical components in their indices of the
      tick number and climate are quite different by their amplitude, value of phase
      displacement, and longevity of terms. However, these structural differences are
      natural and determined by peculiarities of the response reaction of I.
      persulcatus to different intensivity of acting factor. This reaction under
      extreme environment conditions, both minimal and maximal ones, leads to the same
      result, the decreasing of the vital activity and the tick number.

PMID- 9612820
TI  - [The structure and functioning of tick-borne encephalitis foci in the southern
      Far East].
AB  - Based on a statistic data on cases of different clinical forms of the tick-born
      encephalitides in the Russian Far East during 35 years passed it is stated that
      ecological relations in natural foci of this infection have clear and stable
      spatio-temporal specific features and hierarchic structure. The epidemic
      potential of the tick-born encephalitis foci is determined in a great degree by
      conditions of a cold period of year.

PMID- 9612821
TI  - The correspondence between coronary heart disease mortality and risk factor
      prevalence among states in the United States, 1991-1992.
AB  - OBJECTIVE: This study aimed to examine the correspondence between seven
      established risk factors for coronary heart disease (CHD) and CHD mortality among
      the states in the United States. An ecologic analysis relating CHD risk factor
      prevalences to CHD mortality rates among 49 states was undertaken in 1991-1992.
      METHODS: Approximately 68,000 men and women ages 45-74 were randomly sampled and
      interviewed by telephone in surveys conducted in 49 states in 1991 and 1992. From
      these interviews, we estimated state-specific prevalences of smoking, overweight,
      physical inactivity, hypertension, elevated cholesterol, diabetes, and alcohol
      abstinence. These seven CHD risk factors were also combined to create a CHD risk
      index for each state. The main outcome measures were mortality rates from CHD
      (ICD9 codes 410.0-414.9) in each of 49 states in 1991-1992 for men and women ages
      45-74. The analysis was based on multiple linear regression and Spearman's rank
      order correlations between the CHD risk factor prevalences, the combined CHD risk
      index, and the CHD mortality rates among the 49 states. RESULTS: The prevalences
      of most of the CHD risk factors correlated with CHD mortality rates in the
      expected directions, and correlations were similar for men and women. The CHD
      risk index correlated strongly with CHD mortality for both men (r = 0.75) and
      women (r = 0.80). CONCLUSION: About 60% of the variance in CHD mortality between
      the states in the United States (56% for men and 64% for women) is attributable
      to differences between the states in the prevalences of seven established risk
      factors for CHD. As state health agencies prioritize resources for chronic
      disease prevention programs, they should consider the potential benefits of
      increased efforts to reduce the prevalences of modifiable CHD risk factors in
      their populations to reduce CHD mortality.

PMID- 9612822
TI  - Smoking cessation among high school seniors.
AB  - BACKGROUND: Effecting smoking cessation among adolescents provides an opportunity
      to reduce smoking levels among teens and among the adults those teens are soon to
      become. Better understanding of high school students' cessation behavior is
      needed to inform the development of effective strategies to support teen
      quitting. METHODS: Data from 1,210 established smokers among 6,427 12th graders
      from rural and suburban communities in Washington State were used to determine
      the frequency of a declared intention to quit, one or more quit attempts in the
      past year, ongoing quitting, and the attainment of long-term cessation. Logistic
      regression models investigated the association of these outcomes with the extent
      of peer smoking, age of becoming a regular smoker, sex, and grade point average
      (GPA). RESULTS: A serious intention to quit was declared by 67% of established
      smokers, and at least one attempt to quit was made in the past 12 months by 60%.
      However, only 21% of those who had attempted to quit in the past year were still
      abstaining at the time of the survey, and overall, merely 3% had achieved
      cessation beyond 12 months. The likelihood of success of quit attempts was
      strongly dependent on the extent of smoking among peers. Subjects who had become
      regular smokers at the youngest ages were more likely to undertake a quit attempt
      than those who started older. Females were less successful than males in
      attaining ongoing abstinence. Cessation behavior showed no clear association with
      students' GPA. CONCLUSIONS: A high fraction of high school smokers want to quit,
      but are unsuccessful in doing so. Thus, there is a need for programs to provide
      cessation skills to young smokers already motivated to quit.

PMID- 9612823
TI  - Applying multilevel analytic strategies in adolescent substance use prevention
      research.
AB  - BACKGROUND: School-based drug prevention programs have been criticized on
      methodologic grounds because the unit of analysis is often not the unit of
      randomization, thus increasing the likelihood of Type I errors. Application of
      multilevel analytic strategies appropriately corrects this biasing tendency. This
      study demonstrates the practical use of such analysis. METHODS: Data from 2,370
      seventh-grade students participating in a substance use prevention trial were
      analyzed using a multilevel strategy. We examined the effectiveness of a social
      pressure resistance training and a normative education (NORM) intervention
      against an information-only control group. RESULTS: The NORM condition revealed 1
      year program effects for cigarette and marijuana use with individuals as the unit
      of analysis and only marginal effects with classroom as the unit of analysis. No
      program effects were found using school as the analysis unit. A multilevel
      strategy revealed program effects for cigarettes and marijuana with both class
      and school as grouping levels. The effect for alcohol use was significant at the
      2-year follow-up. CONCLUSIONS: Interventions establishing conservative drug use
      norms in classrooms may be an effective strategy in reducing substance use onset
      among adolescents. Utilization of appropriate analytic strategies is important in
      the analysis and interpretation of data containing nested structures.

PMID- 9612824
TI  - The degree and type of relationship between psychosocial variables and smoking
      status for students in grade 8: is there a dose-response relationship?
AB  - BACKGROUND: While most research focuses on simply analyzing the differences
      between smokers and non-smokers, dose-response analyses may be used to find
      evidence of the nature of the association between psychosocial variables and
      involvement with smoking in adolescence. METHODS: For the study, 1,614 grade 8
      students from Scarborough, Ontario, Canada, completed a self-administered
      questionnaire that included items on sociodemographic characteristics, experience
      with smoking, lifestyle, health and weight, work status, and social involvement
      as well as parental education, occupation, and family and peer smoking. A series
      of scales measuring self-esteem, stress, coping, social support, mastery, social
      conformity, and rebelliousness was incorporated. RESULTS: Dose-response
      relationships were evidenced for all categories of variables and were
      demonstrated for the total group and, in most cases, for males and females when
      analyzed separately. CONCLUSIONS: Relationships between variables are not "all or
      none," but may vary depending on amount or level of other factors. These
      relationships provide insight into the mechanisms underlying initiation to,
      maintenance of, and cessation of smoking and should be taken into account in
      programs to reduce or prevent adolescent tobacco use.

PMID- 9612825
TI  - Antecedents of smoking cessation among adolescents: who is motivated to change?
AB  - BACKGROUND: In recent years many longitudinal studies have examined the
      predictors of smoking acquisition. However, only a few studies have focused on
      the precursors of smoking cessation. The current study is one of the first
      concentrating on longitudinal predictors of young people's smoking cessation.
      METHODS: Subjects were 215 smokers ages 14-15 years who were reinterviewed 3
      years later. These smokers were allocated to four groups based on their
      motivation to quit and actual quitting behavior at the last wave. Independent
      variables were smoking-specific cognitions, social influences, and aspects of
      smoking habits. RESULTS: Univariate comparisons between the four groups showed
      that those with a positive attitude toward smoking and lower self-efficacy were
      less likely to be motivated to quit 3 years later. No long-term effects of
      environmental influences were found. Aspects of smoking habits, such as intensity
      and frequency of smoking, and the context of cigarette use affected the
      motivation to quit. Logistic regression analyses were conducted to examine
      differences in predictors between the groups in more detail. These analyses
      revealed that differences mainly in attitudes and self-efficacy affected whether
      subjects were absolutely not motivated to quit or had actually quit 3 years
      later. Differences in smoking behavior affected the allocation to the more
      closely related groups (e.g., preparing versus quitting). CONCLUSIONS:
      Adolescents' motivation to quit is affected by smoking-related cognitions and
      habitual factors. More research is needed to decide whether the relation between
      intensity and frequency of smoking and the likelihood to quit later on should be
      interpreted in terms of differences in smoking initiation or in terms of
      preparation to quit.

PMID- 9612826
TI  - Black-white differences in cigarette smoking uptake: progression from adolescent
      experimentation to regular use.
AB  - BACKGROUND: More U.S. adolescents and young adults have initiated cigarette
      smoking in recent years. Blacks have been less likely than whites to start
      smoking, and the gap has widened recently. Reasons accounting for this large
      black-white difference remain unclear. METHODS: A multiple logistic regression
      analysis was performed using a cohort of 2,467 adolescent smoking experimenters
      ages 11-18, within the 1989-1993 Teenage Attitudes and Practices Survey, a
      nationally representative survey. RESULTS: Among experimenters (1989), 25.7% of
      whites and 10.3% of blacks had progressed to current smoking (1993). The
      unadjusted odds ratio (OR) of progression for blacks (vs whites) was 0.33 [95%
      confidence interval (CI) 0.23, 0.48]. Adjustment for factors significantly
      predictive of progression (most parsimonious model) modified the black-white OR
      to 0.36 (CI 0.24, 0.55), while the full model yielded a black-white OR of 0.39
      (CI 0.24, 0.66). CONCLUSIONS: The observed black-white difference in smoking
      progression was only partly explained by the factors evaluated, and some
      additional factor(s) must be important. Understanding the black-white difference
      in the progression from experimentation to current smoking may help prevent
      uptake among all adolescents.

PMID- 9612828
TI  - How valid is adolescents' self-report as a way of assessing sun protection
      practices?
AB  - BACKGROUND: The accurate assessment of sun protective behaviors can assist in the
      effective targeting of preventive strategies. METHODS: This study explored the
      validity of self-report by adolescents in relation to parental/guardian reports
      using a scale to determine whether adolescents were accurately classified as
      adequately protected or not during the preceding weekend. The study sample was
      drawn from a school population and provided 53 matched adolescent and
      parental/guardian responses from 115 subjects (consent rate 46%). The validity of
      self-reports in relation to the level of protection afforded to a range of body
      parts (face, neck, shoulders, torso, etc.) was calculated. Calculations of
      sensitivity, which represented the proportion of cases in which the body part was
      classified as adequately protected by both the criterion reference and the self
      report, and specificity, in which inadequate protection was confirmed by both the
      criterion reference and the self-report, were completed. In instances in which
      fewer than five observations fell into a cell, thereby limiting the accuracy of
      results, no measures were calculated. RESULTS: Measures of sensitivity for the
      use of sun protection were legs (59%), neck (79%), feet (79%), face (92%), and
      shoulders, torso, and upper arms (98%). In contrast measures of specificity were
      face (61%), legs (80%), and neck (87%). CONCLUSIONS: Although further studies of
      self-report methodologies with larger samples are required to verify these
      findings, the results suggest that adolescent self-report of solar protection is
      relatively valid and has the potential to be utilized with a degree of confidence
      to assess behavior.

PMID- 9612827
TI  - Cigarette smoking in a multiethnic population of youth: methods and baseline
      findings.
AB  - BACKGROUND: To expand upon recent research studies that have identified dramatic
      ethnic differences in adolescent cigarette smoking, this study was designed to
      characterize smoking among a multiethnic population of adolescents and to
      identify significant factors that may protect against smoking initiation.
      METHODS: During the first 2 years, this mixed cross-sectional, longitudinal study
      recruited and collected baseline data from a volunteer sample of 1,441 Houston
      area public school students in the 5th, 8th, or 12th grade. A wide range of new
      and established predictors of smoking behavior was assessed, and their
      associations with ever smoking and susceptibility to smoking were assessed within
      ethnicity (white, N = 537; African-American, N = 454; and Hispanic, N = 297).
      RESULTS: Consistent with previous studies, white students smoked in substantially
      higher proportions than African-American students, with Hispanic adolescents in
      between. Simultaneously adjusting for other variables, the odds of ever smoking
      (OR = 0.47, P < 0.01) and susceptibility to smoking (OR = 0.64, P < 0.01) were
      significantly lower among African-American adolescents when compared with whites;
      odds ratios for Hispanics and whites did not differ. Across all three
      ethnicities, the most important predictor of both ever smoking and susceptibility
      to smoking was the smoking status of the three best friends. Several ethnicity
      specific variables also were identified. CONCLUSIONS: In concordance with
      previous investigations, cigarette smoking prevalence differs by ethnicity, and
      the factors associated with ever smoking and susceptibility to smoking differ
      among white, African-American, and Hispanic adolescents. The results of this
      study may be used to develop theory-based, culturally appropriate smoking
      intervention programs for adolescents.

PMID- 9612829
TI  - The prevalence and predictors of solar protection use among adolescents.
AB  - BACKGROUND: Adolescence has been identified as a critical period in the etiology
      of subsequent melanoma and nonmelanocytic skin cancer. This study examines the
      prevalence and predictors of solar protection use among adolescents. METHODS: A
      total of 3,642 adolescents between the ages of 11 and 16 years were recruited
      from a random sample of 27 schools in an Australian state. The participants
      completed a validated survey that provided information on a range of demographic,
      knowledge, attitudinal, and behavioral factors. Sun protection practices adopted
      during the preceding weekend were assessed using a validated self-report diary. A
      formula that quantifies protection status was then employed to categorize
      adolescents into those who were using adequate versus low levels of solar
      protection. RESULTS: Overall 54% of males and 44% of females were classified as
      adequately protected during the preceding weekend. Logistic regression analyses
      identified the following as significant predictors of having an adequate level of
      sun protection--gender (males more likely to be protected), age (11 to 13 year
      olds more likely to be protected than 14 to 16 years olds), ownership of a broad
      brimmed hat or cap, attitudes relating to the discomfort associated with wearing
      a hat, image to peers, "hassle" associated with the use of sun protective
      measures, school attended, and sun protective policies of the school.
      CONCLUSIONS: Implications of these findings for future preventive strategies are
      discussed and include improved targeting of sun protection programs to non
      adopters, modification of attitudes relating to suntans and image to peers,
      reducing the level of perceived difficulty associated with utilizing sunscreen,
      and the potential role that schools may play in fostering sun protection.

PMID- 9612830
TI  - Reported changes in sexual behavior in response to AIDS in the United States.
AB  - BACKGROUND: The AIDS epidemic has profoundly affected public health policy and
      everyday choices of individuals. Understanding the self-protective strategies
      adopted by the general population is crucial to designing appropriate and more
      effective primary AIDS prevention strategies. METHODS: A probability sample of
      the U.S. adult population in 1992, the National Health and Social Life Survey (n
      = 3,159), addressed detailed aspects of sexual behavior. How respondents changed
      their sexual behavior due to AIDS was recorded verbatim and categorized for
      analysis. RESULTS: Twenty-nine percent of U.S. adults reported some sexual
      behavior change, primarily, reducing numbers of partners (12%), using condoms
      more frequently (9%), selecting partners more carefully (7%), changing attitude
      toward sex (4%), and abstinence (3%). Individuals most at risk show the greatest
      propensity to change although the actual risk-reduction strategies and the
      meanings assigned to those strategies vary considerably. Strategies are not all
      compatible with each other nor equally likely to be adopted by individuals with
      different lifestyles. CONCLUSIONS: Self-protective strategies to avoid AIDS are
      widespread, but primary prevention efforts should be targeted to particular
      circumstances and the self-protective propensities of each individual.

PMID- 9612831
TI  - Predictors of smoking cessation following physicians' counseling.
AB  - BACKGROUND: The purpose of this study was, to identify predictors of quitting
      following general practitioners' (GP) anti-smoking counseling. METHODS: We
      studied determinants (characterized following the Precede framework) of
      successful quitting (1 year sustained abstinence, biochemically confirmed at 6-
      and 12-month follow-up) among 861 smokers randomized to the intervention groups
      based on repeated counseling (RC), RC + spirometric testing, and RC + nicotine
      gum, in a smoking cessation trial carried out in Turin, Italy. RESULTS: GPs'
      intervention worked best for male (OR = 2.30; 95% CI, 1.13-4.52) and married (OR
      = 3.63; 95% CI, 1.37-9.59) smokers, for smokers who had maintained abstinence for
      at least 1 month in the past (OR = 6.78; 95% CI, 1.56-29.52) or at their first
      quit attempt (OR = 10.91; 95% CI, 2.37-50.13), and for those who spontaneously
      reduced their coffee consumption (OR = 3.30; 95% CI, 1.59-6.82); heavy smokers (>
      = 20 cig/day OR = 0.48; 95% CI, 0.24-0.93) and those living with other smokers (>
      = 1 smokers in the household: OR = 0.44; 95% CI, 0.22-0.90) were less likely to
      give up. Previous antismoking advice by the GP represented a strong barrier to
      success for healthy smokers (OR = 0.19; 95% CI, 0.07-0.52), but not for those
      reporting symptoms of shortness of breath (OR = 0.63; 95% CI, 0.39-9.20). There
      were no interactions between predictors and treatment conditions. CONCLUSIONS:
      Assessment of factors influencing quitting would allow GPs to tailor their
      message to address existing barriers and to help patients utilize their resources
      for change.

PMID- 9612832
TI  - Reducing smoking during pregnancy and postpartum: physician's advice supported by
      individual counseling.
AB  - BACKGROUND: Physicians' advice to help pregnant women quit smoking during
      prenatal care has had mixed results. Training and prompting physicians to provide
      consistent advice and referral to on-site support might improve cessation rates.
      METHODS: Pregnant women who smoked were randomly assigned to receive structured
      advice from their physician and referral to individual behavior change counseling
      during prenatal care or to receive brief advice to stop smoking and a quit
      smoking booklet at their first visit. Smoking status was measured by self-report,
      exhaled carbon monoxide, and urinary cotinine. RESULTS: Compared with usual care,
      greater proportions of intervention group women reported not smoking at the 36th
      week visit (14% vs 10%) and at 1 year postpartum (18% vs 11%), but these
      differences were not significant. However, significantly greater proportions of
      intervention group women reported either not smoking or reducing their cigarette
      consumption by 50% or more at their second visit (43% vs 29%, P = 0.02), at their
      36th-week visit (40% vs 25%, P < 0.01), and at 1 year postpartum (26% vs 14%, P =
      0.02). CONCLUSIONS: Physician training on how to gain a pregnant smoker's
      commitment to change her smoking behavior, an office prompt system, and
      individualized smoking behavior change counseling show promise in reducing
      smoking during pregnancy and postpartum, but practical methods to assist pregnant
      smokers between regular prenatal visits, as they attempt to quit, need to be
      developed.

PMID- 9612833
TI  - Smoking status and relative weight by educational level in Finland, 1978-1995.
AB  - BACKGROUND: The aim of the present study was to examine the association between
      smoking status and relative body weight at different educational levels in
      Finland during 1978-1995. METHODS: The data for the study were derived from
      separate cross-sectional health behavior surveys conducted annually by the
      National Public Health Institute (n = 3,418-5,037, response rate 68-84%).
      Relative weight was compared among current smokers, ex-smokers, and never
      smokers. Mean body mass index (BMI) was used as the measure of relative weight.
      Educational level was measured by the number of school years. RESULTS: During
      1978-1995, relative weight increased in all smoking categories. Among men, ex
      smokers weighed most, irrespective of study year or educational level, whereas
      among women ex-smokers showed a mean BMI comparable with that of never smokers.
      Among current and never smokers, both men and women, the association between
      smoking status and mean BMI varied according to educational level: current
      smokers weighed less than never smokers at the lowest educational level, whereas
      at the highest educational level they weighed more than never smokers.
      CONCLUSIONS: The association between smoking status and relative weight varied
      according to educational level. The finding suggests that the association between
      smoking status and relative weight is modified by social and behavioral factors.

PMID- 9612834
TI  - The food intake of smokers and nonsmokers: the role of partner's smoking
      behavior.
AB  - BACKGROUND: To understand the food patterns of smokers, passive smokers, and
      nonsmokers is important for health professionals who are assessing disease risks
      and for those educating individuals regarding healthy lifestyles. This study
      aimed to investigate the role of smoking behavior on the food intake of men and
      women, including the smoking habits of their partner. METHODS: Information on
      food intake and smoking behavior was collected by self-administered
      questionnaires from a cohort of 40- to 70-year-old representatives of the
      suburban Danish population (n = 2,656), cross-sectionally in 1993-1994. RESULTS:
      Men and women who smoked were less frequent consumers of fruit, raw vegetables,
      whole-meal bread, cakes, jam, and tea and were more frequent consumers of white
      bread, meat, coffee, and beer than nonsmokers. The intake frequencies of meat,
      fruit, raw vegetables, whole-meal bread, cakes, jam, coffee, and beer among men
      and of white bread and coffee among women were also associated with their
      partner's smoking behavior, and for these foods, the intakes of subjects living
      with a partner with discordant smoking behavior represented a compromise between
      the food patterns of smokers and nonsmokers. The associations were independent of
      potential confounders such as age, educational level, and physical exercise.
      CONCLUSION: The dietary habits of both men and women are associated with their
      own and their partner's smoking behavior, independent of age, education, and
      exercise. Epidemiological studies of smoking and passive smoking-disease
      relationships should account for the possible confounding by diet.

PMID- 9612835
TI  - Fatal residential fire accidents in the municipality of Copenhagen, 1991-1996.
AB  - BACKGROUND: The death rate for fatal fire accidents in Denmark has doubled since
      1951, mostly due to an increase in the number of fire accidents associated with
      smoking. The most common cause of residential fire deaths in Denmark today is
      smoking, often combined with alcohol intoxication or handicap. METHODS: This was
      a case-control study of fatal fire accidents in private homes in the municipality
      of Copenhagen from 1991 to 1996. The fatal fire accidents were identified from a
      police register, and the two non-fatal fire accidents registered immediately
      before and after each fatal fire were selected as a control group. Information
      about the circumstances surrounding the fires was derived from the police
      reports. Multivariate logistic regression analysis was used to estimate the risk
      associated with each variable after adjusting for confounders. The analysis was
      performed on the basis of the theoretical model in which the variables were part
      of a causal network. RESULTS: The following five variables seemed to be of most
      importance: (1) localization of the victim close to the source of ignition (OR =
      11), (2) physical handicaps (OR = 5), (3) chronic alcoholism (OR = 7), (4)
      clothing fires (OR = 24), and (5) alarm being given by a person not present at
      the scene of fire (OR = 33). Preventive measures are discussed in the light of
      the results.

PMID- 9612836
TI  - Epidemiology of homicide in Allegheny County, Pennsylvania, between 1966-1974 and
      1984-1993.
AB  - BACKGROUND: We compared homicide death rates and characteristics of homicide
      victims and perpetrators in 1966-1974, 1984-1990, 1992-1993, and 1996 in
      Allegheny County, Pennsylvania, in an attempt to detect possible differences in
      the pattern of homicides. METHODS: Data were obtained from death certificates,
      coroner's records, police reports and newspapers. RESULTS: In the 1990s the
      homicide death rate increased for 15- to 24-year-old black men. The rate was 69
      per 100,000/year for black men ages 15-24 years from 1966 to 1974 and rose to 275
      per 100,000 from 1992 to 1993. Currently, the rates appear to be declining again.
      Preliminary data from 1996 showed the number of homicide deaths excluding
      vehicular homicides between 1993 and 1996 to decline from 19 to 8 for white men,
      from 70 to 42 for black men, from 9 to 3 for white women, and from 13 to 6 for
      black women with little change in the population (denominator). The dramatic drop
      from 111 to 61 deaths over a short time is similar to changes across the United
      State and is characteristic of epidemic rise and fall of homicides in the
      community. CONCLUSIONS: Between 1966 and 1993 Allegheny County experienced two
      separate homicide epidemics, one between 1966 and 1976 and the other between 1990
      and 1993. Epidemics of homicide occur frequently and have different
      characteristics. New characteristics of the most recent epidemic of homicide
      include more homicides out of home, among strangers; less association with
      alcohol; and multiple perpetrators. Drug-use-associated homicides have also
      increased. Guns are the primary agents of homicide epidemics.

PMID- 9612837
TI  - Consumption of alcohol in the presence of hepatitis C virus is an additive risk
      for liver damage.
AB  - BACKGROUND: Whether alcohol consumption influences the development of hepatitis C
      in the presence of a latent infection needs to be determined. METHODS: The
      interaction between alcohol intake and hepatitis C virus infection with regard to
      development of liver injury was cross-sectionally investigated for 399
      inhabitants of a town in Nagano Prefecture, Japan. In this town, the prevalence
      of hepatitis C virus infection is 32.4%. RESULTS: The levels of indicators of
      liver function were significantly higher among subjects of both sexes who carried
      the antibody to hepatitis C virus than among those without the antibody. Among
      men, higher levels of liver function were more frequent among alcohol drinkers
      than among nondrinkers, suggesting that alcohol consumption may aid in the
      development of liver injury, even among subjects with a latent hepatitis C virus
      infection. gamma-Glutamyl transpeptidase activity was more sharply increased in
      relation to alcohol intake among subjects with hepatitis C virus infection than
      among those without it, suggesting that the presence of infection will influence
      alcohol-induced liver damage. CONCLUSION: Alcohol consumption and a concomitant
      hepatitis C virus infection apparently facilitate the development of hepatitis.

PMID- 9612838
TI  - Determinants of exercise among children. II. A longitudinal analysis.
AB  - BACKGROUND: Research has demonstrated that physical activity serves an important
      preventive function against the development of cardiovascular disease. The
      recognition that U.S. children are often sedentary, coupled with the observation
      that physical activity habits tend to persist into adulthood, has prompted the
      investigation of exercise determinants consistent with social learning theory.
      The purposes of the present study were to identify social learning variables
      relevant to children's exercise and to explore the longitudinal predictive value
      of the determinants. METHODS: Data were collected from 111 families (N = 54
      girls, N = 57 boys) who were interviewed in both Phase 1 (fifth and sixth grades)
      and Phase 2 (eight and ninth grades) of this study. Data from mothers (N = 111)
      were collected during both phases; data from 80 fathers were collected at Phase 2
      only. RESULTS: The results of simultaneous stepwise regression analyses indicated
      that child's enjoyment of physical activity was the only consistent predictor of
      physical activity during Phase 1. At Phase 2, child's exercise knowledge,
      mother's physical activity, and child's and mother's friend modeling/support
      emerged as predictors for girls. For boys, child's self-efficacy for physical
      activity, exercise knowledge, parental modeling, and interest in sports media
      were important. Longitudinally, mother's self-efficacy, barriers to exercise,
      enjoyment of physical activity, and child's self-efficacy for physical activity
      were important for girls. Only child's exercise knowledge predicted boys'
      physical activity. The addition of information from fathers nearly doubled the
      explanatory power of the predictors for both genders. CONCLUSIONS: Socialization
      in the family unit exerts a tremendous influence on health-related behaviors such
      as exercise. The relative importance of determinants seems to differ for girls
      and boys and the pattern of these determinants appears to change over time.

PMID- 9612839
TI  - Underusers of mammogram screening: stage of adoption in five U.S. subpopulations.
      The NCI Breast Cancer Screening Consortium.
AB  - BACKGROUND: The purpose of this report is to describe the characteristics of
      women ages 50 to 80 who do not follow commonly accepted mammography screening
      guidelines. It provides unique understanding of the robustness of characteristics
      of underusers across five different U.S. subpopulations. METHODS: The data are
      from the baseline surveys of the five studies of the NCI Breast Cancer Screening
      Consortium. Stage of adoption of mammography screening and other characteristics
      of underusers are presented. Polytomous logistic regression analysis was used to
      explore multivariable associations with stage of adoption in each study site.
      RESULTS: The five samples studied by the Consortium range in size from 259 to
      4,477 women (n = 11,292). The relationship of the perceptions of the pros and
      cons of mammography with stage of adoption was strikingly similar across the five
      samples. Other variables consistently associated with stage were a recent receipt
      of a breast physical examination and recommendation for mammography by a
      physician. CONCLUSIONS: The findings suggest a need to encourage regular
      screening through effective communication from a health care provider.
      Intervention messages should be designed to increase the pros of mammography,
      decrease the cons, and highlight these differentially according to the woman's
      stage of adoption.

PMID- 9612841
TI  - Improved screening for breast cancer associated with a telephone-based risk
      assessment.
AB  - BACKGROUND: Our objective was to develop and field-test a telephone-based breast
      cancer risk assessment and to assess its efficacy in improving screening
      behavior. The study was performed at a financial institution and a manufacturing
      corporation with main offices in Boston, Massachusetts, and branch offices in
      various regions of the United States. METHODS: A longitudinal study consisting of
      an initial health risk assessment administered by telephone, with a subsequent
      follow-up study initiated 8 months later, was performed. Study design was
      influenced by some of the suggestions made by the benefits departments of the
      corporate sponsors. A voice-response, telephone system collected risk information
      from callers and gave real-time risk assessment. These callers could receive a
      risk assessment over the phone and remain completely anonymous or furnish name
      and address to receive a more detailed written report. Main outcome measures
      included the response rate and demographics of the respondents, risk profiles of
      the callers, and breast cancer screening statuses. RESULTS: There were 343
      participants of whom 189 relinquished anonymity to receive more detailed
      information by mail and were available for a follow-up study. Sixty-three women
      (18%) reported a family history of breast cancer, with 34 women (10%) responding
      that one first-degree blood relative had been diagnosed before the age of 50. A
      strong positive correlation between the level of familial risk and the decision
      to remain anonymous existed (P < 0.0001). There was an increase in compliance
      with breast self-examination from 34% (40/119) at time of use of the system to
      62% (74/119) at follow-up, P < 0.0001. Clinical breast exams showed similar
      improvements, from 82 (98/119) to 92% (110/119), P < 0.0137. Paired and unpaired
      data of women 40 years of age and older indicate an improvement in mammography
      compliance from time of system use to follow-up, 76 (22/29) to 93% (27/29), P <
      0.0572, and 79 (33/42) to 93% (27/29), P < 0.0129, respectively. CONCLUSIONS: A
      population of women with a risk profile higher than that of the U.S. population
      called the survey. System use is associated with an improvement in breast cancer
      screening habits. Self-reported, increased genetic risk for breast cancer was
      strongly correlated with a decision to remain anonymous.

PMID- 9612840
TI  - Maternal employment and preventive child health practices.
AB  - BACKGROUND: The impact of maternal employment on preventive child health
      practices has not been studied empirically. Using a household production model,
      we investigated the relationship between level of maternal employment and child
      immunization status, use of automobile seat belts, and use of bicycle helmets.
      METHODS: Data from a longitudinal study of public school children in Pinellas
      County, Florida, were used to draw an analytic sample of 4,153 African American
      and white non-Hispanic children whose mothers responded to school surveys in
      1989, 1991, and 1993. Analyses of the relationship between maternal hours worked
      per week and preventive child health practices were performed using multiple
      logistic regression procedures, controlling for maternal age and education,
      household income, ethnicity and gender of child, and number of siblings living at
      home. RESULTS: No significant statistical relationships were found between
      maternal employment and child immunization status or use of automobile seat
      belts. However, maternal employment was significantly associated with bicycle
      helmet use, after controlling for confounders. Children of mothers who worked
      less than 21 h per week were 37% more likely to wear helmets compared with
      children of mothers who worked 21 h or more per week. CONCLUSIONS: Findings
      suggest that children of full-time working mothers are not at greater risk for
      under-immunization or failure to use seat belts regularly, but they may be less
      likely to use bicycle helmets. These results support the hypothesis that
      employment does not affect episodic child health practices but may have some
      negative impact on preventive practices involving daily, repetitive activities.
      It also suggests that the effects of maternal employment may be greater on
      preventive practices that are nonnormative and occur in the absence of adult
      supervision.

PMID- 9612842
TI  - Congenital neuroblastoma in a boy born to a woman with bipolar disorder treated
      with carbamazepine during pregnancy.
AB  - 1. A metastatic neuroblastoma was detected immediately after birth in a boy born
      to a 26 year old woman with bipolar disorder, who received carbamazepine (400
      mg/day) all through her pregnancy. The primary tumor was probably located in the
      adrenal gland of the right side, and multiple metastatic lesions were detected in
      the skin. 2. In this report the authors review the literature about the side
      effects teratogenic and carcinogenic effects of carbamazepine, the epidemiology
      and evolution of the neuroblastoma, and the current scientific opinion about the
      pharmacological treatment of the pregnant with mood disorders. 3. A causal
      relationship between the use of carbamazepine and the neuroblastoma development
      in the present case can not be established; however, as the carcinogenic and
      teratogenic effects of the drug have been basically assessed in epileptic women,
      our aim is to alert the medical community in order to conduct further research in
      psychiatric patients.

PMID- 9612843
TI  - Striatal [125I]RTI-55 binding sites in cocaine-abusing humans.
AB  - 1. Previous experiments in this laboratory found that striatal [3H]WIN 35428
      binding was increased in post mortem specimens from human cocaine users (Little
      et al, 1993a). Although structurally similar, preliminary studies have suggested
      that [3H]WIN 35428 and the related cocaine congener [125I]RTI-55 differ in some
      respects pharmacologically. 2. The present experiments tested the hypothesis that
      striatal [125I]RTI-55 binding would be increased, as was [3H]WIN 35428 binding,
      in post mortem specimens from cocaine users compared to matched controls. 3.
      However, computer-generated parameters derived from saturation experiments found
      only trends toward increased Bmax and decreased affinity (increased KD) in the
      cocaine users. The magnitude of the increases were notably smaller than the
      statistically significant increases previously found in high affinity [3H]WIN
      35428 binding in these same subjects. 4. Evidence from the present and earlier
      experiments suggests that cocaine exposure may induce conformational changes in
      the dopamine transporter.

PMID- 9612844
TI  - Growth hormone secretion during sleep in male depressed patients.
AB  - 1. Growth hormone (GH) secretion during sleep was studied in ten male patients
      with major depression according to DSM III and eight normal controls. 2. Samples
      were collected through a continuous blood withdrawal pump while sleep was
      recorded in the laboratory. 3. The results showed a marked decrease in the GH
      secretion mainly during the first three hours of sleep in depressed patients as
      compared to normal controls. DST and TRH tests were also administered to the same
      patients but no correlation was observed between a positive test and a blunted GH
      secretion, suggesting that the various neuroendocrinological disturbances do not
      coexist in all depressed patients. 4. This disturbance in GH secretion during
      sleep, along with reduced slow wave sleep (SWS), gives support to the theory that
      GHRH is the common stimulus of SWS and GH release and that the ratio of GHRH and
      its counterpart CRH plays a major role in the pathophysiology of disturbed
      endocrine activity during sleep in depression.

PMID- 9612845
TI  - Correlation between steady-state plasma concentrations (Css) of bromperidol and
      haloperidol.
AB  - 1. Bromperidol is a close structural analogue of haloperidol, and its metabolic
      pathways are similar to those of haloperidol. The authors studied the correlation
      between the Css of bromperidol and haloperidol. 2. The subjects were 16
      schizophrenic inpatients. Fourteen patients received firstly bromperidol 12
      mg/day and secondly haloperidol 12 mg/day, while the remaining two patients
      received the two treatments in the opposite sequence. 3. Blood samplings were
      performed 2-3 weeks after the initiation of each treatment, and the Css of
      bromperidol, haloperidol and their reduced metabolites were measured by high
      performance liquid chromatography. 4. Neither the correlation between the Css of
      bromperidol and haloperidol (r = 0.246) nor that between the Css of reduced
      bromperidol and reduced haloperidol (r = 0.142) was significant. 5. The present
      study thus suggests that the Css of bromperidol and haloperidol do not correlate
      well in individuals.

PMID- 9612846
TI  - The effects of lithium on a potential cycling model of bipolar disorder.
AB  - 1. Although bipolar disorder constitutes a major public health problem, with a
      high risk of suicide and an economic cost exceeding that of unipolar depression,
      it has received comparatively little attention, particularly at the basic science
      level. Perhaps as a result of this neglect, there is currently no animal model
      able to simulate the cyclicity which is its defining characteristic. 2.
      Consequently, drug development in this area is meager and has proceeded
      serendipitously rather than empirically. 3. The authors have recently reported
      that repeated exposure to cocaine and other stressors can induce an oscillation
      or cycling in a host of neurochemical and physiological systems. 4. In order to
      test whether such cycling might be of potential relevance to bipolar disorder,
      the authors examined whether cocaine-induced cyclicity of amphetamine-evoked
      efflux of dopamine from slices of rat nucleus accumbens and striatum and/or
      cocaine induced oscillation of a behavior, stress-induced hypoalgesia, could be
      prevented by lithium, the agent of choice in treating this disease. 5. The
      authors report that prophylactic treatment with lithium, completely and
      specifically prevented oscillations in each instance. This may represent an
      important initial step toward the development of the first cycling model of
      bipolar disorder.

PMID- 9612848
TI  - Lithium enhancement of the prolactin response to 5-hydroxytryptophan is not
      reversible by inositol.
AB  - 1. Two hundred male albino Sprague-Dawley rats were studied for the lithium
      and/or inositol effect on 5-HTP induced prolactin release. 2. Lithium
      demonstrated a clear augmentation of 5-HTP induced prolactin levels, however no
      effect of inositol was demonstrated on lithium augmentation of 5-HTP induced
      prolactin release.

PMID- 9612847
TI  - Oscillatory-sensitization model of repeated drug exposure: cocaine's effects on
      shock-induced hypoalgesia.
AB  - 1. The authors have recently proposed that the sensitization produced by repeated
      exposure to drugs or stress may give way to an alternating pattern of increases
      and decreases in the response to each subsequent exposure (i.e., oscillate), as
      the limits of the physiological system are approached. 2. Evidence for
      oscillation has been obtained for 6 drug/non-drug stressors and 9 neurochemical
      or endocrine endpoints. This paper extends the model to a behavioral outcome. 3.
      In the first experiment, rats were given 0, 1, 2 or 3 pretreatments with cocaine
      hydrochloride (COC; 12 mg/kg i.p.), separated by 1-week intervals, and then were
      tested for footshock-induced hypoalgesia (5-sec, 2-mA), as measured by withdrawal
      latencies from a hot-plate. 4. The second experiment replicated the first and
      extended the pretreatment sequence to 5 COC injections. 5. In both experiments,
      shock significantly increased latencies over the no-shock controls. COC enhanced
      shock-induced hypoalgesia and this sensitization reached its maximum after 2 COC
      pretreatments. Thereafter, oscillation developed such that the sensitization was
      attenuated by 3 as compared to 2 COC injections, enhanced by 4 injections, and
      reattenuated after 5 COC pretreatments. 6. These data complement other findings
      by demonstrating that the oscillation model extends to a stress-induced
      behavioral outcome.

PMID- 9612849
TI  - Neuropeptide Y, neurokinin A and neurotensin in brain regions of Fawn Hooded
      "depressed", Wistar, and Sprague Dawley rats. Effects of electroconvulsive
      stimuli.
AB  - 1. Concentrations of neuropeptide Y (NPY)-, neurokinin A (NKA)- and neurotensin
      (NT)-like immunoreactivity (-LI) were measured in brain tissues of Fawn Hooded
      (FH) (a model of depression), Wistar (W) (control for depression) and Sprague
      Dawley (SD) rats (control for strain) with the aim to explore possible
      associations between neuropeptides and models of depression. 2. In addition,
      peptides were determined after six electroconvulsive stimuli (ECS) or six sham
      ECS ("baseline") in order to investigate ECS mechanisms of action. 3. Baseline
      NPY-LI concentrations were markedly lower in the hippocampus of the "depressed"
      FH compared to the W and SD animals. 4. Baseline NKA-LI concentrations were
      higher in the occipital cortex and NT-LI concentrations in the occipital cortex,
      frontal cortex, and hypothalamus of the FH and W compared to the SD rats. 5. ECS
      increased NPY-LI in the hippocampus, frontal cortex and occipital cortex of all
      three strains. In the hippocampus, the increase was significantly larger in the
      FH compared to the W and SD rats. ECS also increased NKA-LI in the hippocampus.
      6. In contrast, ECS decreased NT-LI in the occipital cortex of the FH and W
      animals. 7. The results indicate that NPY may play a role in depression and that
      changes in NPY and NKA probably constitute one of the mechanisms of ECT action.
      More speculatively, NT may also be involved in depression.

PMID- 9612850
TI  - A discriminative stimulus produced by 1-(3-chlorophenyl)-piperazine (mCPP) as a
      putative animal model of anxiety.
AB  - 1. This study compares behavioral responses to serotonergic (5HT) agonists and
      pentylenetetrazol (PTZ) in two behavioral paradigms used as animal models of
      anxiety. PTZ and mCPP were compared for behavioral effects in elevated plus-maze
      and interoceptive discriminative stimuli they produce. 2. PTZ is a known
      anxiogenic drug. The discriminative stimuli of mCPP were selected for comparison
      because this drug produces "anxiety" in human subjects and "anxiety-like"
      behaviors in rats, and is a potent agonist at 5HT1B/2C receptors and a partial
      agonist at 5HT2A receptors. 3. In rats trained to discriminate mCPP (1.4 mg/kg,
      training dose) from saline, PTZ substituted for the mCPP suggesting the "anxiety
      like" properties of the mCPP stimulus. The mCPP stimulus was blocked in a dose
      related manner by methysergide, a 5HT2A/2C antagonist but not by the anxiolytic
      diazepam. TFMPP (a 5HT agonist) and DOI (a 5HT2A/2C agonist) substituted for
      mCPP, but 1-NP (a 5HT1 agonist and 5HT2C/2A antagonist) did not. 4. In animals
      trained to discriminate PTZ (16 mg/kg) from saline, mCPP and DOI substituted for
      PTZ, while TFMPP and 1-NP do not. 5. In the elevated plus maze, time spent on the
      open arms was reduced by mCPP, DOI and PTZ but there was no significant dose
      effect of TFMPP, or 1-NP. 6. Methysergide blocked the "anxiety-like" behavior in
      the EPM. 7. These data suggest that the discriminative stimuli produced by mCPP
      are based upon its selective actions on 5HT receptors and their use in behavioral
      pharmacology may offer another tool in studying pharmacology of 5HT based
      anxiogenic and anxiolytic drugs.

PMID- 9612851
TI  - [Does desensitisation of acetylcholine receptors play a physiological role in the
      neuromuscular synapse?].
AB  - After the acetylcholinesterase inhibition, desensitisation of neuro-muscular
      junctions was found to limit rebundunt activity of postsynaptic membranes and
      disturb normal transmission. Long-term densensitisation of cholinoreceptors
      entails shortening of the postsynaptic current decay due, probably, to a high
      affinity binding the acetylcholine molecules to the desensitised receptors. This
      may prevent repetitive interactions with active receptors and buffer a certain
      amount of acetylcholine.

PMID- 9612852
TI  - [Selective suppression of the direct and feedback "fast" inhibition during local
      administration of picrotoxin in the CA1 region of rat hippocampal slices].
AB  - Application of picrotoxin to apical dendrites in the CA1 area of the rat
      hippocampal slices increased the duration of focal potentials (FP) in the stratum
      radiatum but did not affect the unit activity spikes' amplitude in the stratum
      pyramidalis, the finding suggesting a suppression of the feed-forward inhibition
      with no effect upon the recurrent one. The data obtained shows that, under
      conditions normally used for studying the NMDA-EPSP feed-forward, the inhibition
      is not invariably suppressed and may affect the results of the studies.

PMID- 9612853
TI  - [Amphetamine-induced hyperfunction of the dopaminergic system and delta sleep
      inducing peptide].
AB  - Following amphetamine administration, the DSIP aggravated behavioural patterns
      but the EEG remained unaltered in the visual and motor cortex, and in the caudate
      nucleus. The findings suggest that the peptides modulating action depends on the
      way of dopamine hyperfunction initiation.

PMID- 9612854
TI  - [Reactivity of isolated arteries: the role of their dynamic stretching].
AB  - The smooth muscle constriction elicited by the NA or EFS was smaller when static
      stretching was replaced with a dynamic one in rats. The latter seems to activate
      the NO synthesis/secretion thus inhibiting the constriction and potentiating the
      dilation.

PMID- 9612855
TI  - [Changes in systemic hemodynamics during cardiopulmonary reflex induced by
      administration of the antihypoxic agent].

PMID- 9612856
TI  - [Effect of different regimes of the artificial respiration on systemic
      hemodynamics].
AB  - An increase in artificial lung ventilation induced a suppression in arterial and
      venous portions of the circulation, whereas a limited lung ventilation induced
      pressor shifts of these parameters. The findings suggest that the value of
      respiratory volume per a cycle rather than shifts in the minute respiratory
      volume, affects the values of circulation systemic parameters.

PMID- 9612857
TI  - [Effect of somatostatin on the chronotropic effect caused by vagal nerve
      stimulation by a single stimulus].
AB  - In anesthetised cats, vagal stimulation with a single pulse burst evoked a
      negative chronotropic effect. Somatostatin prolonged the baseline cardiac cycle,
      diminished inhibitory tonic vagal effect, and increased irs latency. This peptide
      effect was associated with a narrowing of an area in the cardiac cycle over which
      even small vagal burst produced a sharp alteration of the sinus node
      responsiveness to vagal influences.

PMID- 9612858
TI  - [Effect of melatonin on the heart rate variability caused by lesions of the
      dorsal hippocampus in rats].
AB  - Bilateral lesions of the hippocampus induced irregular shifts of the heart rate
      variability in rats. The shifts could be prevented with melatonin but not with
      diazepam.

PMID- 9612859
TI  - [Effect of acetazolamide on sodium and potassium absorption in the sheep
      forestomach].
AB  - I.v. Acetazolamide administration suppressed the sodium and potassium absorption
      up to 90 and 100%, resp., in the sheep reticulo-rumen. Absorption of the short
      chain fatty acids was not affected. The findings suggest a sodium/potassium
      exchange processes occurring in the reticulo-rumen epithelium in ruminants.

PMID- 9612860
TI  - [Effects of glycine and glutamic acid on the abomasal evacuatory function in the
      preruminant calf].
AB  - Glycine and glutamic acid were found to exert an effect on the processes of
      abomasal emptying. Following glycine administration, a significant inhibition of
      the evacuation processes occurred with its subsequent activation.

PMID- 9612861
TI  - [Correlation between membrane and soluble forms of intestinal enzymes in rat
      ontogenesis].
AB  - With ageing the membrane/soluble form ratio of membrane-boundenzymes increases
      especially in the ileum and that of peptidases changes rather insignificantly in
      both portions of the rat small intestine. The soluble forms are supposed to take
      part in assimilation of food substrates penetrating enterocytes in an unsplit
      form due to an enhanced permeability of the membranes, particularly those of the
      ileum.

PMID- 9612862
TI  - [The role of M-cholinergic systems in regulation of duration of the post
      inspiratory phase of the respiratory cycle in cats with increased lung volume].
AB  - In decerebrated cats, administration of oxotremorine decreased reflex changes of
      the postinspiratory phase duration in enhancement of the lung volume. Scopolamine
      inhibited the oxotremorine effect. The role of muscarine receptors in these
      phemonena, is discussed.

PMID- 9612863
TI  - [Effect of cold adaptation on lipid metabolism and transport functions of
      skeletal muscle membranes in white rats].
AB  - A prolonged cold adaptation decreased the lipid content and increased free fatty
      acids in homogenate of skeletal muscles. It also seems to decrease the efficiency
      of the calcium-ATPase resulting from non-saturate fatty acids effect upon
      sarcoplasmic reticulum membranes.

PMID- 9612864
TI  - [Effect of phenyl derivative of gamma-aminobutyric acid phenybut on autorhythmic
      contractile activity of the portal vein].
AB  - The phenyl derivative of the GABA phenybute exerts a direct regulating effect
      upon phasic and tonic components of the v.cava autorhythmical contractile
      activity in Wistar rats in media with an altered calcium contents, whereas no
      such effect occurred in hyper-potassium solution or against the background of
      verapamil blockade of the potential-dependent calcium channels.

PMID- 9612865
TI  - [Effect of ethanol and polyethylene glycol-400 on frequency dependence of the
      inotropic effect of verapamil on the frog myocardium].
AB  - The PEG-400 was found to be neutral in respect to the frequency-dependent V
      negative inotropic action whereas ethanol enhanced this dependence. The findings
      suggest a possibility for V inotropic activity to be modified by lipophilic
      agents, provided they sterically complementary to hydrophobic domains of the
      Ca2(+)-channel structure.

PMID- 9612866
TI  - [Effect of kyotorphin on the seizure activity induced by kainic acid during
      picrotoxin kindling in rats].
AB  - In Wistar rats, the ED-50 of kainic acid induced clonic seizures. In early and
      postponed periods of kindling, the ED-50 decreased by 2,0 to 1.5 times.
      Kyotorphin did not affect the ED-50 of kainic acid in postponed periods.

PMID- 9612867
TI  - [Immunologic characteristics of individuals working on the archipelago
      Spitzbergen].
AB  - A complex effect with photo-periodic components and depending on the duration of
      stay on Shpitzbergen Archipelago of people working there, was revealed in respect
      to the serum concentration of Ig A, G, M. The monocytes, autoantibodies, and
      circular immune complexes were increased, whereas lymphocytes, T-cells, and
      natural killers were decreased in winter time.

PMID- 9612868
TI  - [Energy metabolism in students depending on motivation during exams].
AB  - The energy metabolism (EM) was shown to significantly depend upon the motivation
      level in students during examination. Energy expenditure increased before the
      examination in low- and medium motivation groups but not in highly motivated
      students.

PMID- 9612869
TI  - [Passive avoidance conditioning in KHA and KLA rats].

PMID- 9612870
TI  - [The method of study of rheological characteristics of myocardial preparation].

PMID- 9612871
TI  - A Nordic collaboration on medical audit. The APO method for quality development
      and continuous medical education (CME) in primary health care.

PMID- 9612872
TI  - Recurrence rate of streptococcal pharyngitis related to hygienic measures.
AB  - OBJECTIVE: To test the hypothesis that treatment failures of streptococcal
      pharyngotonsillitis may be caused by reinfection by the patients' own
      streptococci remaining on a toothbrush or in the bedclothes. DESIGN: To elucidate
      the role of streptococcal contamination of the environment, hygienic measures
      regarding change of toothbrush and bed linen and washing of toys were given to
      half of the patients/families. Throat specimens were taken from all the patients
      before treatment with phenoxymethylpenicillin for 5 days, and the patients were
      followed-up for 1 month. At a home visit after 6-10 days, throat specimens were
      taken from the patients and all permanent residents of the home. Environmental
      samples were taken from pillowcases, floors, toothbrushes, dummies, and toys.
      SETTING: Six health care centres. SUBJECTS: 114 patients of all ages suffering
      from group A streptococcal pharyngotonsillitis, and 289 family members.
      MEASUREMENTS AND MAIN RESULTS: 54 patients/families received hygiene
      instructions. The total number of recurrences was 40 (35%). There was no
      difference in treatment failure rate between patients/families that had taken or
      not taken hygienic measures. CONCLUSIONS: Hygienic measures have no decisive
      influence on the risk of recurrence of streptococcal pharyngotonsillitis.

PMID- 9612873
TI  - The prevalence of potential pathogenic bacteria in nasopharyngeal samples from
      healthy children and adults.
AB  - OBJECTIVE: To elucidate the prevalence of potential pathogenic bacteria in
      nasopharyngeal samples from healthy individuals, and the influence on the carrier
      rate of age, season of the year, and type of child day care. DESIGN:
      Nasopharyngeal swab samples obtained in routine medical care from individuals
      with no sign of infection were studied in 159 pre-school children aged below 7
      years, 198 schoolchildren aged 7-15 years, and 261 adults (.16 years). RESULTS:
      The prevalence of pathogenic bacteria in healthy individuals decreased with age.
      The overall isolation frequencies for pre-schoolchildren, schoolchildren, and
      adults, respectively, were: Moraxella catarrhalis (27%, 4% and 2%); Streptococcus
      pneumoniae (19%, 6% and 0.8%); Haemophilus influenzae (13%, 6% and 3%). The
      prevalence of S. pneumoniae in children 7-15 years was higher during the summer
      than in the winter. We could not confirm any variation in the carrier rate due to
      the type of child day care. CONCLUSION: Potentially pathogenic bacteria are often
      present in nasopharyngeal samples taken from healthy pre-school children, but
      rarely from people > or = 16 years of age. This means that the use of
      nasopharyngeal samples to discriminate between bacterial and viral respiratory
      tract infection needs to be evaluated further in patients < 16 years. The
      importance of the seasonal variation in the prevalence of potential pathogenic
      bacteria in the nasopharynx needs further study.

PMID- 9612874
TI  - Antibiotic treatment of acute otitis media. Criteria and performance in Danish
      general practice.
AB  - OBJECTIVE: To assess implicit criteria (i.e. what the general practitioner (GP)
      considers good clinical practice) for and performance (i.e. what the GP actually
      does) with regard to antibiotic treatment of acute otitis media in Danish general
      practice. DESIGN: a) Criteria assessed by survey among general practitioners. b)
      Performance assessed by prospective registration of consultations with general
      practitioners related to otitis media. SETTING: General practices in three Danish
      counties. SUBJECTS: a) All the GPs in the three countries (n = 790). b) 368
      children with acute otitis media. MAIN OUTCOME MEASURES: a) Criteria for timing
      of treatment and first drug of choice for acute otitis media; b) prescribed
      antibiotics and multivariate analysis of factors predicting antibiotic
      prescription. RESULTS: a) The response rate was 72%. Only 51% (95% CI 47-55) of
      GPs would give antibiotics to all children with acute otitis media, and 79% (95%
      CI 76-82) of GPs would use penicillin-V as first drug of choice. b) Seventy-four
      per cent (95% CI 68-81) of children with acute otitis media were given
      antibiotics. Factors predicting the GPs' decision to prescribe antibiotics were
      the general condition of the child and the factors that are normally used in
      diagnosing the condition. CONCLUSION: Danish general practitioners' criteria for
      antibiotic treatment of acute otitis media are restrictive, with non-antibiotic
      treatment in cases of short duration and penicillin-V as first drug of choice.
      Performance suggests a less restrictive pattern.

PMID- 9612875
TI  - Predictors of duration of acute sinusitis episodes treated with antibiotics.
AB  - OBJECTIVE: To evaluate which factors present at the onset of acute sinusitis
      predict the duration of illness among adult patients treated with antibiotics.
      DESIGN: Cohort study with a 30-day follow-up. SETTING: Norwegian general
      practice. SUBJECTS: Eighty-six adult patients with a clinical diagnosis of acute
      sinusitis confirmed by Computed Tomography. METHODS: Signs, symptoms and other
      variables present at the onset of treatment were dichotomized and analysed
      bivariately with duration of the sinusitis episode, using the log-rank test. Age,
      gender, and factors with p-values under 0.15 were modelled in a Cox regression
      analysis to assess independent predictors for illness duration. MAIN OUTCOME
      MEASURE: Duration of illness. RESULTS: Illness duration was significantly and
      positively associated with increasing age and with a higher clinical severity
      score at the onset of treatment. No other factors were independent predictors of
      illness duration. CONCLUSION: The age of the patient and the clinical severity of
      the sinusitis at the onset of treatment were independent predictors of illness
      duration in adult patients treated with antibiotics.

PMID- 9612876
TI  - The diagnosis of allergic rhinitis: how to combine the medical history with the
      results of radioallergosorbent tests and skin prick tests.
AB  - OBJECTIVE: To identify the most useful combinations of symptoms and the results
      of radioallergosorbent tests (RASTs) and skin prick tests (SPTs) for the
      diagnosis of allergic rhinitis. DESIGN: A prospective comparison was made of
      symptoms and the results of RASTs and SPTs with 7 different nasal allergies; the
      references used were the "consensus diagnoses" provided by 3 experts. SETTING:
      Nineteen general practices in The Netherlands. PATIENTS: 365 consecutive patients
      aged 12 or over who visited their general practitioner because of chronic or
      recurrent nasal symptoms between 1 March 1990 and 1 March 1991. MAIN OUTCOME
      MEASURES: The most useful combinations of items from the history, RASTs, and
      SPTs, for the diagnosis of 7 different nasal allergies; the predictive
      probabilities of these combinations. RESULTS: Diagnostic criteria could be drawn
      up resulting in a near-perfect discrimination between patients diagnosed as
      having allergic rhinitis and patients diagnosed as not having allergic rhinitis.
      Most of these criteria combined only a single item from the history with either
      RAST or SPT. For nearly all nasal allergies, both the negative predictive
      probabilities and the positive predictive probabilities were 97% or more.
      CONCLUSIONS: The common nasal allergies can be diagnosed with a very high
      certainty with the aid of simple diagnostic criteria. Data from a strictly
      limited case history combined with either RAST or SPT are sufficient.

PMID- 9612877
TI  - Acupuncture in the prophylaxis of recurrent lower urinary tract infection in
      adult women.
AB  - OBJECTIVE: To evaluate the effect of acupuncture in the prevention of recurrent
      lower urinary tract infection (UTI) in adult women. DESIGN: A controlled clinical
      trial with three arms: an acupuncture group, a sham-acupuncture group, and an
      untreated control group. Patients were followed for 6 months. SETTING: An
      acupuncture clinic in Bergen, Norway. SUBJECTS: Sixty-seven adult women with a
      history of recurrent lower UTI. MAIN OUTCOME MEASURES: Acute lower UTIs during
      the 6-month observation period. RESULTS: Eighty-five percent were free of lower
      UTI during the 6-month observation period in the acupuncture group, compared with
      58% in the sham group (p < 0.05), and 36% in the control group (p < 0.01). There
      were half as many episodes of lower UTI per person-half-year in the acupuncture
      group as in the sham group, and a third as many as in the control group (p <
      0.05). CONCLUSION: Acupuncture seems a worthwhile alternative in the prevention
      of recurring lower UTI in women.

PMID- 9612879
TI  - Diabetic patients in primary health care--quality of care three years apart.
AB  - OBJECTIVE: To compare registering of diabetic complications and metabolic control
      in diabetic subjects in primary health care in 1992 and 1995. DESIGN: Cross
      sectional surveys of medical records. SETTING: Three community health centres in
      Stockholm County. SUBJECTS: Diabetic patients aged 18-84 years in 1992 (n = 177)
      and in 1995 (n = 413). MAIN OUTCOME MEASURES: Rate of noted diabetic
      complications and metabolic values. RESULTS: Retinopathy examination was noted in
      64% in 1992 versus 65% in 1995, neuropathy examination in 44 versus 49%, and
      urine examination in 88% versus 73% (p < 0.001). HbA1c was examined in 52% in
      1992 versus 68% (p < 0.001) in 1995, fasting blood glucose in 89 versus 90%, and
      cholesterol in 34 versus 42%. Acceptable HbA1c values were noted in 51% in 1992
      versus 46% in 1995. Smoking habits were available in 26% in 1992 versus 53% in
      1995 (p < 0.001) and BMI in 5 versus 39% (p < 0.001). Diabetic blindness was
      present in 2.2% in 1995, uraemia in 0.3%, and amputation due to gangrene in 1.2%.
      CONCLUSION: Documented examination rates of diabetic patients are unacceptably
      low, and the metabolic level unsatisfactory in most cases. Severe complications
      are, however, rare.

PMID- 9612878
TI  - Serum lipoprotein(a) and cardiovascular disease in non-insulin-dependent diabetes
      mellitus.
AB  - OBJECTIVE: To examine whether lp(a) can explain a) the increased cardiovascular
      morbidity in patients with non-insulin-dependent diabetes mellitus (NIDDM) and b)
      the wide variation in the tendency for such complications to develop in the
      patients. DESIGN: Cross-sectional study. SETTING: General practice in a local
      community in Norway. SUBJECTS: One hundred and thirty NIDDM patients and a
      reference group drawn from a twin study. MAIN OUTCOME MEASURES: Lp(a), self
      reported cardiovascular disease, urinary albumin excretion. RESULTS: The level of
      lp(a) was equally distributed in our NIDDM population and a reference group. We
      found no association between lp(a) and self-reported cardiovascular disease and
      urinary albumin excretion (UAE). CONCLUSION: Lp(a) cannot explain the increased
      risk for cardiovascular disease in NIDDM patients, nor can it explain the
      variation in the tendency for such complications to develop.

PMID- 9612880
TI  - The reliability and validity of doctor-recorded morbidity data in active data
      collection systems.
AB  - OBJECTIVE: To test the reliability and validity of morbidity data recorded by
      general practitioners (family physicians) on structured recording forms in active
      data collection systems. DESIGN: The consulting general practitioner recorded the
      problems managed at 347 video-taped doctor-patient contacts. Two observers
      independently viewed the video-tapes and completed a recording form for each.
      Problems were centrally coded, using the International Classification of Primary
      Care (ICPC). SETTING: Primary health care. MAIN OUTCOME MEASURES: Overall
      distribution of the morbidity; positive agreement regarding the morbidity managed
      at matched contacts at three levels of specificity (chapter; chapter-component;
      specific rubric); agreement taking negative agreement into account using Cohen's
      Kappa. RESULTS: Overall distribution of morbidity did not differ between
      observers. Positive mean agreement was 78.8% at chapter level, 69.6% at chapter
      component, and 55.9% at rubric level. Kappa statistics showed agreement better
      than chance in all chapters, but failed to reach significance at rubric level in
      three chapters. CONCLUSION: Morbidity data actively collected by GPs provide a
      reliable overview of morbidity managed in general practice. At a specific contact
      the morbidity recorded is reliable and valid at chapter level, and in most cases,
      at chapter-component level. At rubric level variance between practitioners in
      labelling the problem calls into question the validity and reliability of the
      data.

PMID- 9612881
TI  - Task profiles of district doctors in Estonia and general practitioners in
      Finland.
AB  - OBJECTIVE: To compare the task profiles of primary care doctors in two societies:
      district doctors in Estonia and general practitioners in Finland. DESIGN: A
      uniform questionnaire was developed and used in 30 European countries in 1993
      (The European Study of GP Task Profiles). The questionnaire was sent to a random
      sample of Estonian district doctors and Finnish health centre doctors. Data from
      139 respondents in Estonia and 239 respondents in Finland were obtained. MAIN
      OUTCOME MEASURES: Personal and practice information, proportion of doctors
      performing certain medical procedures in their practices by themselves and being
      the first contact in relation to different problems. RESULTS: The Finnish general
      practitioners (GPs) had more consultations per day, the Estonian district doctors
      made remarkably more home visits. Participation in on-duty work was 82% among the
      Finnish and 22% among the Estonian doctors. Most of the Finnish GPs worked by
      appointment, while this was uncommon in Estonia. More than 80% of the Estonian
      district doctors reported that they seldom or never performed the listed
      procedures by themselves. In Finland, more than 80% of the respondents carried
      out the procedures almost always by themselves. Handling children's and women's
      health problems was more frequent in Finland than in Estonia. The profiles of
      managing acute problems and problems of the elderly people were quite similar in
      both countries. The tackling of psychosocial problems as the first contact showed
      lower performance in both countries compared with somatic health problems.
      CONCLUSIONS: The task profiles of the Estonian district doctors and the Finnish
      GPs differed considerably. The distribution of the Estonian doctors' answers
      gives evidence for the existence of specialization already within primary health
      care where certain problems almost never reach the district doctor. The results
      of the present study supported the curriculum design for the retraining of
      currently practising district doctors.

PMID- 9612882
TI  - Diagnostic methods in dyspepsia: the usefulness of upper abdominal ultrasound and
      gastroscopy.

PMID- 9612883
TI  - Working conditions and family situation in relation to functional
      gastrointestinal disorders.

PMID- 9612884
TI  - Modelling ordinal responses from co-twin control studies.
AB  - The co-twin control design has been widely used in studying the effects of
      environmental factors on the development of diseases. For binary outcomes that
      arise from co-twin control studies, the conditional likelihood method is commonly
      used. This approach, however, does not readily extend to ordinal response data
      because the standard conditional likelihood does not exist for cumulative logit
      or proportional odds models. In this paper, we investigate the applicability of
      the random-effects and GEE approaches in analysing ordinal response data from co
      twin control studies. Using both approaches, we re-analyse data from a co-twin
      control study of the impact of military services during the Vietnam era on post
      traumatic stress disorders (PTSD). The ordinal models have considerably increased
      power in detecting the effects of exposure when compared to the analyses using a
      dichotomized response. We discuss the interpretation of the estimates from GEE
      and random-effect models in the context of the twin data.

PMID- 9612885
TI  - An extended Kaplan-Meier estimator and its applications.
AB  - We develop an extension of the Kaplan-Meier estimator for the case of multiple
      live states. The method can be used to construct prognostic charts for tracking
      individuals initially in a given condition. It is also the key component in
      constructing a longitudinal version of the multistate life table.

PMID- 9612886
TI  - Assessment of covariate effects in Aalen's additive hazard model.
AB  - We study the properties of test statistics for a covariate effect in Aalen's
      additive hazard model and propose several new test statistics. The proposed
      statistics are derived by using the weights from linear rank statistics for
      comparing two survival curves. We compare these statistics with the two
      statistics proposed by Aalen using Monte Carlo simulations. Several different
      survival configurations are considered in the simulation study: proportional
      hazards; crossing hazards; hazard differences early in time, and hazard
      differences for large survival times. Of the proposed test statistics, one is
      superior for detecting hazard differences for large survival times and another is
      superior for detecting early hazard differences and crossing hazards.

PMID- 9612887
TI  - Parametric likelihoods for multiple non-fatal competing risks and death.
AB  - Clinical trials of fatal diseases often focus on one or more non-fatal events, in
      addition to survival, both to characterize morbidity and to improve survival
      estimates. Three statistical complications are that the time to each non-fatal
      event and subsequent residual survival may be either positively or negatively
      associated, the times to death with or without an antecedent event often have
      very different distributions, and death may censor some of the non-fatal event
      times. Consequently, the overall survival time distribution is a mixture of the
      distributions corresponding to the possible antecedent non-fatal events. These
      conditions violate the usual assumptions underlying many statistical methods for
      analysing multivariate time-to-event data. In this paper, we consider a general
      parametric model for multiple non-fatal competing risks and death. The model
      accounts for positive or negative association between the time of each non-fatal
      event and subsequent survival while accommodating covariates and the usual
      administrative censoring. Each event time distribution is specified marginally by
      a three-parameter generalized odds rate model, and the time of each non-fatal
      event and subsequent residual survival are combined under a bivariate generalized
      von Morgenstern distribution. The approach is illustrated by application to two
      data sets from clinical trials in colon cancer and acute leukaemia.

PMID- 9612888
TI  - Flexible assessment of trends in age-specific HIV incidence using two-dimensional
      penalized likelihood.
AB  - We present a method for estimating age- and time-specific HIV incidence using
      back-calculations of AIDS incidence data. Two-dimensional penalized likelihood is
      employed, using a flexible bivariate step function model of HIV incidence,
      together with a quadratic roughness penalty which leads to thin-plate spline
      smoothing. This allows incidence estimates to vary flexibly and smoothly in both
      age and time. We propose generalized cross-validation as a guide for choice of an
      appropriate level of smoothing and describe an EM algorithm for computing the
      estimates. We propose the method primarily for qualitative assessment of trends
      in age-specific incidence over time and apply it to a small Italian data set on
      men who have sex with men. The analysis suggests a trend over time of increasing
      relative incidence among younger individuals, consistent with incidence patterns
      observed in other countries.

PMID- 9612889
TI  - Maximum likelihood estimation of receiver operating characteristic (ROC) curves
      from continuously-distributed data.
AB  - We show that truth-state runs in rank-ordered data constitute a natural
      categorization of continuously-distributed test results for maximum likelihood
      (ML) estimation of ROC curves. On this basis, we develop two new algorithms for
      fitting binormal ROC curves to continuously-distributed data: a true ML algorithm
      (LABROC4) and a quasi-ML algorithm (LABROC5) that requires substantially less
      computation with large data sets. Simulation studies indicate that both
      algorithms produce reliable estimates of the binormal ROC curve parameters a and
      b, the ROC-area index Az, and the standard errors of those estimates.

PMID- 9612890
TI  - Adjusting Moran's I for population density.

PMID- 9612891
TI  - Testing for treatment differences with dropouts present in clinical trials--a
      composite approach.

PMID- 9612892
TI  - Bias in the evaluation of DNA-amplification tests for detecting Chlamydia
      trachomatis.

PMID- 9612893
TI  - [Instrumental investigations in diagnosis: advances and risk of technical
      progress in medicine].

PMID- 9612895
TI  - [Noninvasive investigation of endothelial function in patients with hypertension
      and hypercholesterolemia (HCE)].
AB  - AIM: Functional assessment of endothelium by endothelium-dependent and non
      endothelium dependent response of the brachial artery (BA) in patients with risk
      factors for atherosclerosis. MATERIALS AND METHODS: The ACUSON 128 XP/10 unit
      furnished with linear meter with phase grid (7.0 MHz) was employed in two
      direction scanning mode to measure BA diameter at rest, under reactive hyperemia
      (endothelium-dependent response) and after sublingual intake of 0.01 mg of
      nitroglycerin (non-endothelium-dependent response) in 12 patients with blood
      hypertension (group 3), 10 subjects with family hypercholesterolemia (group 2)
      and 10 healthy subjects (group 1, control). RESULTS: The flow-dependent
      dilatation remained unchanged in BH patients (9.4%) and lowered in HCE patients
      (3.0%) compared to controls (9.5%). Nitroglycerin-induced dilatation was not
      significantly different in patients with family hypercholesterolemia (16.6%),
      hypertensive subjects (14.5%) and healthy controls (20.5%). CONCLUSION: The
      ultrasound method of detection of endothelial dysfunction is demonstrated.
      Endothelial dysfunction in patients with familial hypercholesterolemia may
      contribute to development of atherosclerosis.

PMID- 9612894
TI  - [Biochemical diagnosis of hereditary hyperlipoproteinemias].
AB  - AIM: To specify characteristics of lipoproteins (LPs) metabolism in patients with
      diverse forms of hereditary hyperlipoproteinemia (HLP) and determine biochemical
      tests for their differential diagnosis. MATERIALS AND METHODS: According to the
      criteria of polygenic hypercholesterolemia (PHCE), family combined hyperlipidemia
      (FCHL), family hypertriglyceridemia (FHTG) and family hypercholesterolemia
      (FHCE), 157 patients were selected aged 7 to 70 years of 192 examinees (76
      patients with primary HLP and 116 their close relatives). Lipids were measured by
      enzyme methods, apoproteins (apo)--by immunoturbidimetry and immune diffusion.
      RESULTS: Compared to healthy subjects, PHCE patients were characterized by higher
      apoB level and proportion cholesterol (CS)/apoB in very low and low density
      lipoproteins (VLDL and LDL). In unchanged level of high density lipoprotein (HDL)
      CS and proportion HDLP CS/apoA1 there were reduced quantities of free HDLP CS,
      HDLP2 CS and apoA1. In FHCE and FCHL there were also low levels of HDL CS in
      elevated ones of apoE in (VLDL + LDL). However, in FCHL, contrary to FHCE, the
      proportion SC (VLDP + LDL)/apoB was as in control group. FHTG patients differed
      from healthy subjects by diminished HDL parameters: lower HDL CS due to free CS
      and its esters, apoA1 and proportion HDL Cs/apoA. There were no differences with
      controls by content of apoB and proportion CS (VLDL + LDL)/apoB, apoE levels in
      different class lipoproteins. CONCLUSION: Biochemical parameters are proposed
      which can differentiate various forms of hereditary hyperlipoproteinemia.

PMID- 9612896
TI  - [Clinical and prognostic significance of late ventricular potentials in patients
      with hypertrophic cardiomyopathy].
AB  - AIM: Evaluation of clinical and prognostic value of late ventricular potentials
      (LVP) in patients with hypertrophic cardiomyopathy (HCMP) regarding the
      arrhythmic and structural-functional characteristics. MATERIALS AND METHODS: 60
      HCMP patients were studied: 16, 32 and 12 with apparent, latent and absent
      obstruction of left ventricular outflow tract. Among other clinical tests, the
      patients underwent echocardiography with dopplerography and Holter 24-h
      monitoring. LVP were registered at signal-averaged electrocardiography. The
      results were defined as abnormal in the presence of at least 2 of 3 standard LVP
      criteria: FORS > 114 ms, LAS > 38 ms, RMS 40 < 20 microV. RESULTS: LVP occurred
      in 9(15.0%) patients. All of them had obstructive HCMP (3 cases of definite and 6
      cases of latent HCMP). The absence of LVP proved to be a favorable prognostic
      factor indicating weak probability of development of electric myocardial
      unstability, syncopal states and sudden death of arrhythmic genesis. CONCLUSION:
      The occurrence of LVP in HCMP is not closely related to structural-functional
      condition of the heart. Detection of LVP is not a reliable predictor of sudden
      arrhythmic death risk.

PMID- 9612897
TI  - [Dynamic electrophysiological examination of heart in patients with sick sinus
      syndrome in continuous pacing].
AB  - AIM: Dynamic electrophysiological examination of the heart with allowances for
      ECG variants of this syndrome and stimulation regimen was performed to predict
      the results of continuous pacing in patients operated for sick sinus syndrome
      (SSS). MATERIALS AND METHODS: 32 patients had the diagnosis of bradycardia SSS
      (group 1), 15 patients--bradytachycardia (group 2). 30 patients were on
      ventricular VVI stimulation, 17 patients--on atrial AAI stimulation.
      Electrophysiological examination of the heart was performed by means of
      transesophageal left atrial pacing under programmed, frequent and ultrafrequent
      stimulation 1, 2, 3 and 4 years after the start of continuous cardiac pacing.
      RESULTS: In group 2 depression of the sinus function (corrected time of the sinus
      function recovery, frequency of spontaneous pacemaker, duration of
      poststimulation pause) under pacing was more distinct than in group 1.
      Deterioration of atrioventricular conduction was greater in group 1. Three and
      four years after pacing the Wenckebach point in group 1 lay significantly lower
      than in group 2. Within the follow-up period 6 (12.8%) patients developed AB
      block of the second degree. 4 patients of them were from group 1. Arrhythmogenic
      atrial readiness depended on the kind of cardiac affection more than on
      stimulation regimen. CONCLUSION: Dynamic electrophysiological cardiac examination
      in the presence of pacing allows following up of natural course of sick sinus
      syndrome and early correction of the stimulation regimen.

PMID- 9612898
TI  - [Echocardiographic evaluation of mitral system and complications of mitral
      prolapse].
AB  - AIM: The analysis of echo-CG morphology of the mitral system in patients with
      uncomplicated mitral prolapse (MP) in the presence and absence of mitral
      regurgitation and in patients with severe complications. MATERIALS AND METHODS:
      Echo-CG was made in 116 patients with MP: with uncomplicated (87) and complicated
      (29) MP, with infectious endocarditis (13), thromboembolism (6), congestive
      circulation failure (10). MP was diagnosed according to the standard criteria
      with visualization of the mitral valve from the parasternal approach. RESULTS:
      Mitral picture is detailed for 87 MP patients. Classification of the degree of
      myxomatous degeneration is proposed. 17 MP patients were exposed to loading
      echocardiography. Exercise may provoke transitory mitral regurgitation. Mitral
      status has been analysed in patients with serious MP complications. CONCLUSION:
      The relationship may exist between MP complications, severity of myxomatous
      degeneration of the mitral valve and the presence of any kind of mitral
      regurgitation.

PMID- 9612899
TI  - [Activity of renin-angiotensin-aldosterone system (RAAS) and vasopressin level in
      patients with primary pulmonary hypertension].
AB  - AIM: Assessment of RAAS and vasopressin in patients with primary pulmonary
      hypertension (PPH). MATERIALS AND METHODS: Activity of plasma renin (APR),
      angiotensin-converting enzyme (ACE), plasma levels of angiotensin II (AII) and
      vasopressin (VP), serum concentration of aldosteron (AS) were measured by
      radioimmunoassay and enzyme immunoassay in 21 PPH patients with circulatory
      failure (age 34.7 +/- 2.1 years), 11 patients with NYHA functional class II-III,
      10 with class IV, and 10 control subjects (age 29.8 +/- 1.5 years). RESULTS:
      Compared to controls, 21 PPH patients had elevated RAAS parameters: APR up to
      3.52 ng/ml/h (p < 0.05), activity of ACE up to 43.13 units, AII level up to 33.93
      ng/ml (p < 0.01), AS up to 468.86 ng/ml (p < 0.01), VP up to 5.26 ng/ml (p <
      0.001). Circulatory failure progression resulted in activation of all the RAAS
      components. This and VP activation was the greatest in PPH patients with ACE > 5
      ng/ml/h. PPH patients with mean pressure in the pulmonary artery higher than 60
      mm Hg demonstrated higher ARP, AS, VP, AII, ACE than those who had this pressure
      under 60 mm Hg. CONCLUSION: PPH patients display a noticeable activation of RAAS
      and VP. This activation seems to be secondary as the changes increase with
      elevation of the pressure in the pulmonary artery and aggravation of circulatory
      insufficiency. Plasma renin activity determines the degree of RAAS activation as
      a whole. The discovered activation of RAAS in PPH gives grounds for doubts in the
      validity of using ACE inhibitors in the treatment of PPH.

PMID- 9612900
TI  - [Effectiveness of differential diagnosis of benign and malignant ulcers at
      endoscopy].
AB  - AIM: Assessment of efficacy of differential diagnosis between benign and
      malignant lesions in gastric mucosa by means of endoscopy. MATERIALS AND METHODS:
      Morphological verdicts upon investigation of operative specimens were compared to
      findings at preoperative duodenofibrogastroscopy with spot biopsy in 326 patients
      operated for gastric ulcer. The number of discrepancies between the endoscopic
      and morphological diagnoses enabled estimation of endoscopy + biopsy efficiency
      in identification of the ulcer malignancy. RESULTS: The number of diagnostic
      errors made on malignant or benign nature of ulcer at endoscopic and biopsy
      investigations is rather big, i.e. at least 12% for both false negative and false
      positive hypophyses. The overall diagnostic efficacy of endoscopy in detection of
      the disease lies within 65-80%. CONCLUSION: Reliability of endoscopic
      identification including biopsy of malignant nature of gastric ulcers is not very
      high. Real sensitivity of this method in detection of ulcers undergoing malignant
      transformation reaches 76-78%.

PMID- 9612901
TI  - [Cholestasis assessment by activity of antioxidant enzymes and composition of
      plasma lipoproteins in patients with liver diseases].
AB  - AIM: Investigation of activity of copper-containing enzymes in plasma superoxide
      dismutase (SOD) and ceruloplasmin (CP) in comparison with concentrations of
      lipoproteins (LP) of the main classes in patients with chronic hepatic diseases
      (CHD). MATERIALS AND METHODS: SOD activity, CP and LP in plasma were measured in
      90 patients with CHD. RESULTS: An inverse relationship was found between SOD
      activity and CP content in CHD. SOD/CP ratio proved informative in cholestasis
      assessment. An increased ratio beta-LP/alpha-LP was noticed in patients with
      primary biliary cirrhosis. This value and the disease severity correlated.
      CONCLUSION: Patients with cholestatic hepatic lesions exhibited inhibition of
      enzyme utilization of superoxide radicals in plasma in line with enhancement of
      CP secretion.

PMID- 9612902
TI  - [Determination of natural antibodies to catecholamines in health and disease].
AB  - AIM: Enzyme immunoassay (EIA) determination of the level of natural antibodies (n
      Ab) to catecholamines in patients with metabolic disturbances and cardiovascular
      diseases, correlation between content of n-Ab to these bioregulators and clinical
      diagnosis, biochemical indices. MATERIALS AND METHODS: EIA with specially
      synthetized artificial antigens was used to determine n-Ab to catecholamines
      (adrenaline, noradrenaline, dopamin) in 41 patients with cardiovascular diseases
      and metabolic disturbances (ischemic heart disease, essential hypertension,
      hyperlipoproteinemia) and in 10 healthy subjects (donors, controls). RESULTS:
      Changes in the levels of antibodies to catecholamines correspond to the clinical
      diagnosis. Interrelations exist between n-Ab to catecholamines and biochemical
      parameters in the disease. CONCLUSION: The trends in the amount of n-Ab to
      catecholamines are a unique marker of metabolic disturbances of these endogenic
      substances and can be used in diagnosis.

PMID- 9612904
TI  - [Clinical and diagnostic significance of microalbuminuria and activity of tubular
      enzyme N-acetyl-beta-D-glucosaminidase (NAG) determination in patients with
      hyperuricosuria].
AB  - AIM: Development of the approaches to detection of hyperuricosuric stage of purin
      metabolism derangement and specification of methods for early diagnosis of urate
      damage to the kidney. MATERIALS AND METHODS: The study included 115 young
      subjects whose parents suffer from gout with renal involvement or isolated urate
      nephropathy. Each patient was examined clinically with evaluation of family
      history for gout risk factors. Three times for 9 months measurements were made of
      uricemia and uricosuria, microalbuminuria and activity of tubular enzyme NAG.
      RESULTS: 45 (39.1%) patients had neither disturbances of purin metabolism nor
      renal affection. 70 (60.9%) patients had hyperuricosuria. In 23 (32.9%) of them
      microalbuminuria increased to > 20 mg/day, NAG activity to 5 u/l. Chronic
      tubulointerstitial nephritis was diagnosed in 17 (73.9%) patients. Six patients
      (26.1%) developed asymptomatic affection of the kidneys. The rest 47 patients had
      normal levels of microalbuminuria and NAG. There were 3 cases of hyperuricemia
      with microalbuminuria rising to 160-200 mg/day and further development of urinary
      syndrome. Hyperuricemia in them was registered at microalbuminuria higher that
      160 mg/day. CONCLUSION: Microalbuminuria higher than 20 mg/day and NAG activity
      higher than 5 u/day are important diagnostic indicators of renal affection in
      hyperuricosuria including asymptomatic one. Microalbuminuria above 160 mg/day
      gives grounds to discuss the role of morphological changes prior to proteinuria.

PMID- 9612903
TI  - [Polymerase chain reaction in diagnosis of cytomegalovirus infection in patients
      with organ allotransplants].
AB  - AIM: Investigation of potentialities of polymerase chain reaction (PCR) in
      diagnosis of cytomegalovirus infection in recepients of allotransplants.
      MATERIALS AND METHODS: PCR with primers on the MIE region was used to examine the
      blood of recepients of the kidney, heart, hemodialysis patients, donors (199, 6,
      35 and 67 subjects, respectively) for DNA of cytomegalovirus (CMV). RESULTS: CMV
      DNA was found in none of the donors, 95 recepients. Severity of clinical symptoms
      in blood carriers of CMV correlated with the level of DNA CMV (p < 0.001). 85% of
      those with high levels of DNA CMV (1000 per 10(5) leukocytes) had acute clinical
      symptoms. 15.8% of all the PCR-positive patients had no symptoms at the time of
      the examination. Specific antivirus ganciclovir therapy was given to 50% of PCR
      positive patients and to 85% of those who had DNA CMV higher than 1000 c. per
      10(5) leukocytes. The treatment resulted in a sharp fall or disappearance of DNA
      CMV and symptoms of CMV disease. CONCLUSION: PCR can be applied in diagnosis of
      CMV infection in allotransplants recepients.

PMID- 9612905
TI  - [Current aspects of diagnosis and treatment of atopic diseases complicated by
      secondary immunodeficiency].
AB  - AIM: The study of clinicoimmunological features of current course of atopic
      diseases (AD) and design of effective etiopathogenic scheme of treating AD
      complicated by secondary immunodeficiency (SID). MATERIALS AND METHODS: After
      comprehensive clinical, instrumental, x-ray, functional and bacteriological
      investigations 186 AD patients were divided into 4 groups: 25 patients untreated
      by immunomodulators (controls), 35 patients treated by diuciphone (200 g i.m.
      each other day for 12 days), 83 patients treated by polyoxidonium (6 mg i.m. each
      other day for 12 days, a total course dose 30 mg, or 6 mg i.m. daily for 2 days
      then 6 mg each other day for 3 days then 6 mg twice a week for 14 days, a course
      dose 45 mg), 33 patients received likopid (1 or 10 mg daily per os for 10 days or
      10 mg daily for 10 days then 2 mg twice a week for 14 days). RESULTS: A scheme of
      combined 3-staged treatment of AD complicated by SID is suggested. Stage 1
      conventional treatment inhibiting aggravation of atopic reaction, improving
      functional condition of the defense systems plus antiinfection therapy,
      immunomodulators. Stage 2-primarily specific immunotherapy. Stage 3-outpatient
      prophylaxis of immunodeficiency and resistant forms of atopic reactions.
      CONCLUSION: Combined staged pharmacological and immunological control of allergic
      inflammation and immunodeficiency is the main principle of control of AD with
      SID.

PMID- 9612906
TI  - [Difficulties of tuberculosis diagnosis in patients with systemic blood
      diseases].

PMID- 9612907
TI  - Differential diagnosis of infectious diseases with hemorrhagic syndrome.

PMID- 9612908
TI  - [Formulation of clinical diagnosis in purulent peritonitis].

PMID- 9612909
TI  - [Treatment and prevention of iron deficiency anemia in outpatient practice].

PMID- 9612910
TI  - [Objective assessment methods of coronary arteries balloon angioplasty].

PMID- 9612911
TI  - [Granulocytic colony-stimulation factor granocyte and its clinical application].

PMID- 9612912
TI  - Studies on the efficacy of hyperbaric rendering procedures in inactivating bovine
      spongiform encephalopathy (BSE) and scrapie agents.
AB  - The efficacy of the procedures in use at the two rendering plants in the
      Netherlands was assessed on a laboratory-scale using procedures that simulated
      the pressure cooking part of the rendering process. A pool of bovine spongiform
      encephalopathy (BSE)-infected brainstem from the United Kingdom and a pool of
      scrapie-infected brainstem from Dutch sheep were used to spike the rendering
      materials. The mixtures were subjected to various time-temperature combinations
      of hyperbaric heat treatment related to the conditions used in Dutch rendering
      plants in the early 1990s, and to the combination of 20 minutes at 133 degrees C
      required by the EU Directive on rendering of 1996. The efficacy of the procedures
      in inactivating BSE or scrapie infectivity was measured by titrating the
      materials before and after heat treatment in inbred mice, by combined
      intracerebral and intraperitoneal inoculations at limiting dilutions. Two
      independent series of experiments were carried out. The design of the study
      allowed for minimum inactivations of up to 2.2 log (2.0 in the second series) to
      be measured in the diluted infective material and 3.1 log in the undiluted
      material. After 20 minutes at 133 degrees C there was a reduction of BSE
      infectivity of about 2.2 log in the first series (with some residual infectivity
      detected), and in the second series more than 2.0 log (with no residual
      infectivity detected). With undiluted brain material there was an inactivation of
      about 3.0 log (with some residual infectivity detected). With the same procedure,
      scrapie infectivity was reduced by more than 1.7 log in the first series and by
      more than 2.2 log in the second series. With undiluted brain material there was
      an inactivation of more than 3.1 log. In each case no residual scrapie
      infectivity was detected. The BSE agent consistently appeared to be more
      resistant to heat inactivation procedures than the scrapie agent, particularly at
      lower temperatures and shorter times.

PMID- 9612913
TI  - Acute phase toxoplasma abortions in sheep.
AB  - Within 13 days of the experimental infection of 15 oestrus-synchronised ewes with
      2000 sporulated oocysts of Toxoplasma gondii at 80 to 90 days of gestation 11 had
      aborted. The infection induced pyrexia and specific antibody in all the ewes. One
      ewe resorbed its fetus, 11 ewes aborted and three delivered, at full term, live
      congenitally infected lambs whose pre-colostral serum was antibody-positive.
      Tissues from the aborted fetuses and placentae from the live lambs were examined
      for toxoplasma infection by polymerase chain reaction (PCR) amplification of the
      B1 gene and by mouse inoculation. The live lambs were all shown to be infected by
      both methods, but there was no evidence of infection in any of the tissues from
      the acute phase abortions, suggesting that these fatalities occurred before the
      placenta or the fetus had been invaded by T gondii. Such toxoplasma-induced,
      acute-phase abortions are likely to be impossible to diagnose from fetal tissues.
      These results have implications not only for the diagnosis of naturally occurring
      ovine abortions but also for the understanding of the pathogenesis of toxoplasma
      induced abortion.

PMID- 9612914
TI  - Porcine dermatitis and nephropathy syndrome in Spain.
AB  - In August 1995, the first case of porcine dermatitis and nephropathy syndrome was
      diagnosed in the north-eastern part of Spain; the pig showed characteristic
      dermal and renal lesions. Between then and January 1996, nine further animals
      from five different herds were diagnosed; they showed signs of anorexia,
      depression and, sometimes, pyrexia. Diarrhoea, Glasser's disease, conjunctivitis
      and gastric ulcers also occurred on the farms where the diagnoses were made. The
      affected pigs died of renal failure with diffuse fibrinous glomerulonephritis and
      a systemic necrotising vasculitis. Chronic interstitial nephritis,
      glomerulosclerosis and scar-like marks on the skin were observed in chronic
      cases. Other common findings in both acute and chronic cases were a diffuse
      depletion of lymph node lymphocytes with infiltration by syncytial cells (50 per
      cent of cases) and interstitial pneumonia. All the animals tested positive for
      porcine reproductive and respiratory syndrome virus (PRRSV) by serological tests
      and virus isolation. Serum urea and creatinine concentrations were above normal
      in the acutely affected animals. The pathogenesis of the condition is unknown but
      the lesions and immunopathological observations by other authors suggest that a
      type III hypersensitivity is a possible aetiology. The occurrence of PRRSV in
      these pigs suggests that the virus might be implicated in the pathogenesis of
      porcine dermatitis and nephropathy syndrome.

PMID- 9612915
TI  - Pathophysiology of Oestrus ovis infection in sheep and goats: a review.
AB  - Oestrus ovis is a very common parasite of sheep and goats in many countries. Its
      pathological effects are often underestimated because owners and veterinarians
      are used to seeing the infection. The study of natural and experimental
      infections has provided information about the evolution of the disease and its
      pathophysiology. Hypersensitivity is involved; the numbers of mast cells and
      eosinophils increase but changes in IgE have only recently been examined. Little
      is known about the development of immunity but it is possible that some animals
      are immunodeficient.

PMID- 9612916
TI  - Preclinical detection of PrPSc in nictitating membrane lymphoid tissue of sheep.

PMID- 9612917
TI  - Comparison of a rapid immunomigration test and ELISA for FIV antibody and FeLV
      antigen testing in cats.

PMID- 9612918
TI  - Diabetes mellitus associated with lymphocytic pancreatitis in a cow.

PMID- 9612919
TI  - Funding veterinary education.

PMID- 9612920
TI  - Porcine circovirus infection in Northern Ireland.

PMID- 9612921
TI  - Detection of strangles carriers.

PMID- 9612922
TI  - Tail-biting and tail-docking in pigs.

PMID- 9612923
TI  - Erythromycin, a motilin agonist, increases postprandial gallbladder emptying
      during therapy with ursodeoxycholic acid.
AB  - Sufficient gallbladder emptying accelerates early gallstone clearance after
      extracorporeal shock wave lithotripsy (ESWL). Litholytic therapy with
      ursodeoxycholic acid (UDC) subsequent to ESWL increases fasting volume (FV) and
      postprandial residual volume (RV) of the gallbladder. This may lead to retention
      of cholesterol crystals and small fragments within the gallbladder. In order to
      find out whether erythromycin, a motilin agonist, improves gallbladder emptying,
      we tested gallbladder motility after administration of ursodeoxycholic acid with
      and without oral application of erythromycin. Ten healthy males (age 26-35 years)
      obtained 10 mg/kg/d of UDCA as a single bedtime dose for three weeks. Prior and
      after UDCA administration, gallbladder FV was determined sonographically after
      overnight fasting. After a test meal (490 kcal), gallbladder volume was measured
      every 5 min until the gallbladder had reached its minimal RV. The next day the
      same procedure was repeated with 500 mg erythromycin p.o. 45 min prior to test
      meal application. FV, RV, ejection volume (EV = FV-RV) and ejection fraction (EF
      = EV/FV x 100) were calculated and differences were compared by the student's t
      test. FV (29 ml +/- 8 ml vs. 38 ml +/- 10 ml), RV (12 ml +/- 6 ml vs. 17 ml +/- 6
      ml) and EV (17 ml +/- 5 ml vs. 21 ml +/- 6 ml) increased significantly during
      therapy with UDCA (p < 0.05). EF did not change significantly. After erythromycin
      application RV decreased to its original values (13 ml +/- 6 ml), whereas EV (24
      ml +/- 6 ml) and EF (58% +/- 9% vs. 66% +/- 11%) increased significantly (p <
      0.05). Thus, administration of a motilin agonist blunts unwanted effects on
      gallbladder motility during litholytic therapy with UDC.

PMID- 9612924
TI  - Interobserver agreement in defecography--an international study.
AB  - BACKGROUND: Defecography is considered to be an essential investigation in the
      evaluation of functional anorectal disorders, but the agreement between observers
      from different clinical centers has never been evaluated. METHODS: 14
      defecographic studies were selected aimed to cover the most relevant
      defecographic findings responsible for disordered defecation. Eight studies were
      considered unequivocal, but six were thought to be controversial. All were sent
      to the ten participants in Europe and the US (five proctosurgeons, three
      radiologists, two gastroenterologists). They evaluated the studies using a
      previously agreed upon questionnaire. Interobserver agreement was quantified by
      kappa statistics and by the proportions of positive and negative agreement as
      compared to chance agreement, respectively. RESULTS: Overall, only the
      completeness of rectal emptying and the presence of a rectocele achieved
      acceptable kappa values above 0.4. When restricting the evaluation to the studies
      considered to be unequivocal, agreement improved considerably and was moderate to
      good for all items describing the images (kappa 0.43-0.63). However, whether
      proctosurgery should be performed and whether defecography contributed to the
      management of the particular patient remained controversial with very low kappa.
      CONCLUSIONS: It is doubtful whether defecography contributes substantially to the
      management of patients with disordered defecation.

PMID- 9612925
TI  - The role of enteroclysis in the diagnosis of unexplained gastrointestinal
      symptoms: a prospective assessment.
AB  - The purpose of this prospective study performed at a non-university hospital was
      to assess the role of enteroclysis in the diagnosis of unexplained
      gastrointestinal symptoms such as abdominal pain, gastrointestinal bleeding, and
      chronic diarrhea done following inconclusive imaging or endoscopic procedures.
      184 consecutive patients were subjected to enteroclysis over 25 months. 84 (46%)
      had abdominal pain, 52 (28%) gastrointestinal bleeding, and 48 (26%) chronic
      diarrhea. Findings were categorized as normal and abnormal (subdivided into main,
      i.e., explanatory of symptoms; and secondary, i.e., not explanatory of symptoms).
      Main findings were further divided into those exclusively detected by
      enteroclysis and those confirmed by this procedure. Normal enteroclysis
      investigations were obtained in 159 (86%) patients and abnormal in 25 (14%). Main
      findings were present in 19 (10%) patients, in ten (5%) of them exclusively
      detected by enteroclysis. Secondary findings were present in six (3%) patients,
      also detected only by enteroclysis. The highest rate of main findings exclusively
      detected by enteroclysis related to patients with chronic diarrhea (8%), compared
      with 6% and 2% with abdominal pain and gastrointestinal bleeding, respectively.
      For the inspection of the small bowel, enteroclysis shall remain the gold
      standard for detecting abnormal findings in the small bowel until user-friendly
      enteroscopes are developed.

PMID- 9612926
TI  - Short-term efficacy and long-term outcome of cyclosporine treatment in patients
      with severe ulcerative colitis.
AB  - Cyclosporine A (CyA) has been recommended for the treatment of severe steroid
      resistant ulcerative colitis, however, long-term results are scarce. We
      prospectively followed a treatment plan in 14 patients with severe ulcerative
      colitis receiving intravenous CyA after failure to respond to at least eight days
      of standard therapy with prednisolone (1-1.5 mg/kg/day). CyA was delivered in a
      daily dose of 5 mg/kg i.v. for a mean of 14 days (range 7-28) in addition to
      ongoing medical therapy. CyA whole blood levels were monitored by HPLC and
      maintained between 100 ng/ml and 400 ng/ml. Responders were switched to oral CyA
      (5-7.5 mg/kg/day) for a mean of two months, and steroids were gradually tapered.
      Eleven patients (79%) initially responded to i.v. CyA, three patients failed to
      respond and underwent urgent colectomy. Time until response averaged seven days
      (range 3-13). Four of the eleven responders underwent colectomy because of severe
      relapse after one, eleven, twelve and 13 months of follow-up. The remaining seven
      patients were followed for a median of 48 months. During the first year of follow
      up three out of seven had a severe relapse and responded to steroids (two
      patients) or to a further course of i.v. CyA (one patient). During CyA therapy
      one patient developed staphylococcal sepsis, other adverse events were mild and
      reversible. The results confirm that CyA is effective in severe steroid
      refractory ulcerative colitis. Severe relapse and colectomy are uncommon after
      the first year of follow-up and the colon preserving effect of CyA can be
      maintained in up to 50% of patients over a period of four years.

PMID- 9612927
TI  - [Rare cause of acute pancreatitis: phytobezoar in an intraluminal diverticulum in
      type I duodenal atresia, intestinal malrotation and rudimentary pancreas
      anulare].
AB  - A 28-year-old woman was hospitalized because of the third episode of acute
      pancreatitis. No hint for an extrinsic cause was evident. Under conservative
      treatment pancreatitis and signs of intestinal obstruction were persisting.
      Imaging procedures showed an undefinite mass in the neighbourhood of the
      pancreatic caput. Endoscopy revealed a phytobezoar in a wind sock web, a special
      form of congenital duodenal atresia. Obstructing the papilla of Vater the bezoar
      had caused acute pancreatitis. After endoscopical removal the symptoms of
      pancreatitis disappeared immediately. Web excision and duodenoduodenostomy were
      performed. At operation further anomalies of the gastrointestinal tract
      frequently associated with duodenenal atresia were found.

PMID- 9612928
TI  - [Barrett esophagus with severe dysplasia in argon beam therapy].
AB  - A curative therapy of Barrett's esophagus is not established, yet. However, in
      prospective clinical research trials, a combined therapy of potent
      pharmacological acid suppression with superficial coagulation of metaplastic
      epithelium is examined. By local coagulation using photodynamic therapy, laser or
      argon plasma coagulation, a complete reconstitution of squamous epithelium should
      be achieved. We report on a case of a patient with Barrett's esophagus and low
      grade dysplasia, who developed high-grade dysplastic cell formations under argon
      plasma coagulation therapy. As part of a clinical study, the patient was treated
      over a period of one year monthly. We monitored the result of the therapy over
      the period of one year with endoscopy, histolgical investigations and DNA image
      cytometry. Ultimately a decision in favour of a further surgical management was
      made. The diagnostic instruments to identify patients with a high risk for the
      development of adenocarcinoma are discussed.

PMID- 9612929
TI  - [Current aspects of pathogenesis, diagnosis and therapy of primary MALT stomach
      lymphomas].
AB  - Primary gastrointestinal lymphoma of MALT occupy a special position which is
      documented in their own histological classification. Our knowledge about
      pathogenesis, biological and therapeutical behaviour of this lymphoma entity has
      increased substantially during recent years. Considering epidemiological,
      histomorphological and experimental data Helicobacter pylori infection
      undoubtless plays an important role in the development and progression of gastric
      MALT-lymphoma. In view of histological malignancy (low or high grade) and
      dissemination of the disease (stage) as decisive prognostic factors and
      therapeutical determinants endoscopic-bioptical diagnosis as well as endoscopic
      ultrasound are of major importance. In case of localized low-grade lymphoma
      eradication of Helicobacter pylori offers a promising therapeutic option.
      Surgical resection and radiochemotherapy have proven to be effective treatment
      modalities. There is a need for randomized trials to clarify if operative or
      conservative therapeutic strategies have to be favored in the future.

PMID- 9612930
TI  - Assessment of afferent gut--brain function using cerebral evoked responses to
      esophageal stimulation.
AB  - Increasing awareness is attributed to altered sensory perception in the
      pathogenesis of gastrointestinal disorders. Evoked potentials (EP), which
      represent the brain's electrical response to peripheral stimulation, have
      recently been used to investigate where and how (GI) afferent information is
      processed along the brain-gut axis. EP can be obtained with electrical
      stimulation or balloon distention in the esophagus in humans. Stimulation of
      afferent neural pathways in the esophagus produces cerebral evoked responses
      allowing assessment of the peripheral afferent neural pathways involved, and of
      the function of integrative neural centers within the brain. Recent studies using
      esophageal EP indicate that the cerebral response to either mode of stimulation
      depends on the perception of the stimuli. Using electrical stimulation, a clear
      dose-response relationship is found. The EP response obtained with electrical
      stimulation is in keeping with those recorded using direct cervical stimulation
      of the vagus nerve, supporting evidence that esophageal EP are produced by
      activation of afferent vagal pathways. From the conduction velocity of the
      autonomic (vagal) nerves conveying information from esophagus to brain, it was
      concluded that non-painful electrical stimuli predominantly activate fast
      conducting myelinated afferent sensory fibers (A-fibers), while EP to balloon
      distention are largely due to activation of unmyelinated C-fibers. Techniques,
      however, vary widely amongst different investigators, and some
      electrophysiological parameters remain controversial, as there is no standard
      approach. Using balloon distention, EP waveforms vary widely between
      laboratories, suggesting that EP are substantially influenced by the stimulator
      devices (pump, respirator). EP to balloon distention are hampered by a relatively
      low signal-to-noise ratio (SNR), which is probably due to long inflation
      deflation time (> 200 ms). With electrical stimulation, there is much less
      variability between different groups, and SNR is distinctly higher. This method
      appears to be most attractive for studies of afferent esophageal function.
      Standardization of the techniques is important, before esophageal EP can be
      regarded as a useful diagnostic approach in patient groups.

PMID- 9612931
TI  - [To stick or not to stick--a reliable urine test in pancreatitis?].

PMID- 9612932
TI  - [Clinical effectiveness of short-term administration of monoclonal antibody cA2
      against tumor necrosis factor alpha in Crohn disease].

PMID- 9612933
TI  - [Antibody-mediated inhibition of migration into the colon results in a decrease
      of by T-cell transfer-induced colitis in SCID mice].

PMID- 9612934
TI  - Cytochrome P450 purification and immunological detection in an insecticide
      resistant strain of German cockroach (Blattella germanica, L.).
AB  - A German cockroach strain, Munsyana (MA) had 80-fold resistance to the pyrethroid
      insecticide cypermethrin, 4.5-fold greater total cytochrome P450 content and 2.5
      fold greater cytochrome P450-mediated N-demethylation of 4-chloro-N-methylaniline
      compared to the susceptible Johnson Wax (JWax) strain. Immobilized artificial
      membrane high performance liquid chromatography (IAM-HPLC) of microsomal proteins
      from the MA strain enriched cytochrome P450 greater than 70-fold. Following
      purification, a single protein band of M(r) = 49,000 (P450 MA), was detected by
      silver-staining SDS PAGE gels. Antiserum to the purified protein from the MA
      strain (anti-P450 MA) was produced in mice. Anti-P450 MA inhibited cytochrome
      P450-mediated N-demethylation by 4-fold in both MA and JWax strains. In Western
      blots of microsomal proteins, anti-P450 MA differentiated single MA and JWax
      individuals by recognizing and M(r) 49,000 protein band in only the MA strain. In
      JWax cockroaches, the M(r) 49,000 band was only detectable in Western analysis
      following induction with pentamethylbenzene (PMB). PMB induction also increases N
      demethylation 2.6 and 8.0-fold in the MA and JWax strains, respectively. These
      results are consistent with the hypothesis that insecticide resistance in the MA
      strain is due to over-expression of a cytochrome P450.

PMID- 9612935
TI  - Complete sequence, expression, and evolution of the hexamerin LSP-2 of Calliphora
      vicina.
AB  - In cyclorraphan Diptera, two different types of hemolymph proteins exist which
      belong to the hexamerin family. During the last larval instar, Calliphora vicina
      synthesizes, besides the major fraction of arylphorin, a second hexameric
      protein, LSP-2. Here the developmentally regulated biosynthesis of this protein
      was analyzed. Western blot analyses showed that LSP-2 is not present in eggs,
      1st, and 2nd instar larvae, whereas it can be detected in all tissues of last
      instar larvae. We report the characterization of the complete cDNA sequence that
      encodes a LSP-2 subunit, a nascent polypeptide of 701 amino acids with a
      molecular mass of 83.16 kDa. By Northern blotting, a mRNA of about 2.2 kb coding
      for LSP-2 is identified exclusively in the fat body of 3rd larval instars
      reflecting the stage and tissue specificity of LSP-2 gene expression.
      Phylogenetic analysis demonstrates the existence of two distinct groups of
      hexamerins in Diptera.

PMID- 9612936
TI  - Expression of Schistocerca gregaria ion transport peptide (ITP) and its homologue
      (ITP-L) in a baculovirus/insect cell system.
AB  - We expressed an N-terminally extended Schistocerca gregaria ion transport peptide
      (ScgITP) and its homologue (ion transport peptide-like; ITP-L) in insect Sf9
      cells using baculovirus expression vectors. Antibodies raised against peptide
      fragments of ITP and ITP-L were used to detect and characterize the baculovirus
      expressed peptides (bacITP, bacITP-L). Biological activity of the expressed
      peptides was assayed using the highly specific bioassay for native ITP, namely
      the increase in ileal short-circuit current which is a measure of active Cl-
      transport. BacITP and bacITP-L expression was optimal in Sf9 cells infected at a
      multiplicity of infection of 1, grown in Grace's medium, and harvested 2-3 days
      after infection. Western blots showed that bacITP was 2 kDa larger than native or
      synthetic ITP. This difference was not due to glycosylation and could in part be
      attributed to post-translational cleavage of the ITP propeptide at a site 11
      amino acids upstream of the cleavage site used by S. gregaria to produce native
      ITP. BacITP stimulated ileal short-circuit current but is significantly less
      active (270-fold) than synthetic ITP (synITP) possibly as a result of the N
      terminal extension. Production of bacITP-L permitted us to show that it is not
      stimulatory in the bioassay but reduces the synITP response in vitro and thus may
      have some potential for enhancing the effectiveness of biological control agents
      such as baculoviruses.

PMID- 9612937
TI  - Methods to obtain quantitative parametric descriptions of the optical surfaces of
      the human crystalline lens from Scheimpflug slit-lamp images. I. Image processing
      methods.
AB  - Of the methods developed (e.g., phakometry, magnetic resonance imaging, etc.) for
      noninvasive measurement of the geometry of the anterior segment of the human eye,
      Scheimpflug photography offers the best resolution and the highest precision. The
      primary obstacle encountered with this or any other image-based method has been
      in obtaining quantitative measurements directly from the images. Image
      enhancement (gray-scale gradient analysis) and pattern recognition methods (Hough
      transform and recursive least-squares algorithms) are developed so that
      parametric representations of lens surfaces and zone boundaries can be obtained
      directly from the images. Methods to correct for nonlinear Scheimpflug camera
      reproduction ratios and provide error estimates for geometrical parameters are
      also developed and will be presented separately. Combined, these techniques yield
      representations of lens geometry having sufficient precision, to which paraxial
      ray tracing can be applied to determine lens optical properties by using well
      posed optical models with one unknown.

PMID- 9612938
TI  - Spatial-frequency tuning of visual contour integration.
AB  - We examine the mechanism that subserves visual contour detection and particularly
      its tuning for the spatial frequency of contour components. We measured the
      detection of contours composed of Gabor micropatterns within a field of randomly
      oriented distractor elements. Distractors were randomly assigned one of two
      spatial frequencies, and elements lying along the contour alternated between
      these values. We report that the degree of tolerable spatial-frequency difference
      between successive contour elements is inversely proportional to the orientation
      difference between them. Spatial-frequency tuning (half-width at half-height) for
      straight contours is approximately 1.3 octaves but, for contours with a 30
      degrees difference between successive elements, drops to approximately 0.7
      octaves. Integration of curved contours operates at a narrower bandwidth. Much
      orientation information in natural images arises from edges, and we propose that
      this narrowing of tuning is related to the reduction in interscale support that
      accompanies increasing edge curvature.

PMID- 9612939
TI  - Light-intensity distribution in eccentric photorefraction crescents.
AB  - We try to improve the accuracy of eccentric photorefraction by taking more
      information into account than just the size and tilt of the crescent. Based on
      Gaussian optics and the assumption of an isotropic scattering retina, a
      theoretical analysis of the light-intensity distribution in the pupils of
      astigmatic eyes is presented. The method is applied to different photorefractor
      setups (point light source, long linear light source, knife-edge aperture, and
      circular aperture). In the case of a knife-edge aperture the crescent structure
      can be formulated analytically. In the case of a circular aperture an analytic
      description is possible only for spherical refractive errors, but astigmatic
      refractive errors can be determined from crescent parameters with neural
      networks.

PMID- 9612940
TI  - Objective assessment of image quality. III. ROC metrics, ideal observers, and
      likelihood-generating functions.
AB  - We continue the theme of previous papers [J. Opt. Soc. Am. A 7, 1266 (1990); 12,
      834 (1995)] on objective (task-based) assessment of image quality. We concentrate
      on signal-detection tasks and figures of merit related to the ROC (receiver
      operating characteristic) curve. Many different expressions for the area under an
      ROC curve (AUC) are derived for an arbitrary discriminant function, with
      different assumptions on what information about the discriminant function is
      available. In particular, it is shown that AUC can be expressed by a principal
      value integral that involves the characteristic functions of the discriminant.
      Then the discussion is specialized to the ideal observer, defined as one who uses
      the likelihood ratio (or some monotonic transformation of it, such as its
      logarithm) as the discriminant function. The properties of the ideal observer are
      examined from first principles. Several strong constraints on the moments of the
      likelihood ratio or the log likelihood are derived, and it is shown that the
      probability density functions for these test statistics are intimately related.
      In particular, some surprising results are presented for the case in which the
      log likelihood is normally distributed under one hypothesis. To unify these
      considerations, a new quantity called the likelihood-generating function is
      defined. It is shown that all moments of both the likelihood and the log
      likelihood under both hypotheses can be derived from this one function. Moreover,
      the AUC can be expressed, to an excellent approximation, in terms of the
      likelihood-generating function evaluated at the origin. This expression is the
      leading term in an asymptotic expansion of the AUC; it is exact whenever the
      likelihood-generating function behaves linearly near the origin. It is also shown
      that the likelihood-generating function at the origin sets a lower bound on the
      AUC in all cases.

PMID- 9612941
TI  - Assessing and optimizing the performance of a phase-shifting interferometer
      capable of measuring the complex index of refraction and the surface profile of a
      test surface.
AB  - A novel interferometer based upon a conventional phase-shifting design is further
      investigated. This interferometer is capable of measuring both the real and
      imaginary parts of the complex index of refraction and the surface profile of a
      test surface. Maximum-likelihood estimation theory is shown to be an effective
      means of extracting the three parameters of interest from the measured data.
      Cramer-Rao lower bounds are introduced as a means of quantitatively assessing the
      performance of the system. Furthermore, it is shown that as the design parameters
      are optimized, the results approach the theoretical performance limit. We
      conclude by developing the underlying theory behind the relationship of the
      complex-index-of-refraction estimates to the surface-profile estimate.

PMID- 9612942
TI  - Expression of maize and fungal nitrate reductase genes in arbuscular mycorrhiza.
AB  - The role of arbuscular mycorrhizal (AM) fungi in assisting their host plant in
      nitrate assimilation was studied. With polymerase chain reaction technology, part
      of the gene coding for the nitrate reductase (NR) apoprotein from either the AM
      fungus Glomus intraradices or from maize was specifically amplified and
      subsequently cloned and sequenced. Northern (RNA) blot analysis with these probes
      indicated that the mRNA level of the maize gene was lower in roots and shoots of
      mycorrhizal plants than in noncolonized controls, whereas the fungal gene was
      transcribed in roots of AM plants. The specific NR activity of leaves was
      significantly lower in AM-colonized maize than in the controls. Nitrite formation
      catalyzed by NR was mainly NADPH-dependent in roots of AM-colonized plants but
      not in those of the controls, which is consistent with the fact that NRs of fungi
      preferentially utilize NADPH as reductant. The fungal NR mRNA was detected in
      arbuscules but not in vesicles by in situ RNA hybridization experiments. This
      appears to be the first demonstration of differential formation of transcripts of
      a gene coding for the same function in both symbiotic partners.

PMID- 9612943
TI  - Agrobacterium tumefaciens transformation and cotransformation frequencies of
      Arabidopsis thaliana root explants and tobacco protoplasts.
AB  - In view of the recent finding that different T-DNAs tend to ligate and integrate
      as repeats at single chromosomal positions, the frequency of transformation and
      cotransformation was determined during cocultivation of Arabidopsis thaliana root
      explants and Nicotiana tabacum protoplasts with two Agrobacterium strains. The
      transformation frequency of unselected A. thaliana shoots was lower than 1%
      whereas that of cocultivated tobacco protoplasts was approximately 18%. The
      cotransformation frequencies, defined as the frequencies with which cells
      transformed with a first T-DNA contained a second unselected T-DNA, were
      approximately 40% reproducible, irrespective of the selection, the transformation
      frequency, and the plant system used. Extrapolation of these results suggests
      that at least two independently transferred T-DNAs were present in 64% of the
      transformed plant cells. Molecular analysis of cocultivated N. tabacum shoots
      regenerated on nonselective medium showed that only a few transformants had a
      silenced (2/46) or truncated (1/46) T-DNA. Therefore, most integrated T-DNAs
      expressed their selectable or screenable markers in primary transgenic plants.
      Remarkably, 10 to 30% of the selected A. thaliana shoots or progenies lost the T
      DNA marker they were selected on. As these regenerants contained the unselected T
      DNA with a high frequency (17%), these selected plants might result from the
      expression of unstable, transiently expressed T-DNAs. In conclusion, a
      significant part of the T-DNAs is lost from the transformed cells.

PMID- 9612944
TI  - The plasma membrane H(+)-ATPase from the biotrophic rust fungus Uromyces fabae:
      molecular characterization of the gene (PMA1) and functional expression of the
      enzyme in yeast.
AB  - To study the molecular basis of biotrophic nutrient uptake by plant parasitic
      rust fungi, the gene (Uf-PMA1) encoding the plasma membrane H(+)-ATPase from
      Uromyces fabae was isolated. Uf-PMA1 exists probably as a single gene. However,
      two nearly identical sequences were identified; the similarity apparently is due
      to two Uf-PMA1 alleles in the dikaryotic hyphae. Multiple Uf-PMA1 transcripts
      were observed during early rust development, and reduced amounts of a single Uf
      PMA1 mRNA were observed in haustoria and rust-infected leaves. This is in
      contrast to elevated enzyme activity in haustoria compared to germinated spores
      (C. Struck, M. Hahn, and K. Mendgen. Fungal Genet. Biol. 20:30-35, 1996).
      Unexpectedly, the PMA1-encoded rust protein is more similar to H(+)-ATPases from
      plants (55% identity) than from ascomycetous fungi (36% identity). When the rust
      PMA1 cDNA was expressed in Saccharomyces cerevisiae, both the wild-type enzyme
      and a mutant derivative (delta 76) deleted for the 76 C-terminal amino acids were
      able to support growth of a yeast strain lacking its own H(+)-ATPases. Compared
      to the wild-type, the delta 76 mutant enzyme displayed increased affinity to ATP,
      a higher vanadate sensitivity, and a more alkaline pH optimum. These results
      indicate that the C-terminal region of the rust enzyme exhibits auto-regulatory
      properties.

PMID- 9612945
TI  - Xanthomonas campestris pv. campestris requires a functional pigB for epiphytic
      survival and host infection.
AB  - When cauliflower plants (Brassica oleraceae) were misted with bacterial
      suspensions of Xanthomonas campestris pv. campestris (causal agent of black rot
      of cruciferous plants), two separate populations of the pathogen were associated
      with the leaves. Initially, bacteria removable by sonication and sensitive to
      sodium hypochlorite treatment predominated (easily removable epiphytic bacteria,
      EREB). However, after 2 weeks, bacteria not removable by sonication and
      insensitive to sodium hypochlorite treatment were dominant. Although the exact
      location of this second population of the pathogen was not determined, evidence
      is presented to support its location in protected sites on the leaf surface, pigB
      of this pathogen is required for production of extracellular polysaccharide
      (EPS), xanthomonadin pigments, and the diffusible signal molecule, DF (diffusible
      factor). DF can extracellularly restore EPS and xanthomonadin production to pigB
      mutant strains. Parent strain B-24 and pigB mutant strain B24-B2 were identical
      for in planta growth and symptomatology after artificial infection by injection
      in leaf mid-veins. Subsequently, X. campestris pv. campestris parent strain B-24,
      Tn3HoHo1 pigB insertion mutation strain B24-B2, chromosomally restored pigB
      mutation strain B24-B2R, and strain B24-79 with a Tn3HoHo1 insertion in an
      unrelated part of the genome were compared for epiphytic survival on, and natural
      infection of, cauliflower. After application, strains B-24, B24-B2R, and B24-79
      all maintained leaf EREB populations of between approximately 3 and 6 (log [1 +
      CFU per g of fresh weight]) over a 3-week period, whereas B24-B2 populations fell
      to nearly undetectable levels. Plants sprayed with strains B-24, B24-B2R, and B24
      79 averaged between 1.0 and 1.2 lesions, whereas those sprayed with B24-B2
      averaged only 0.03 lesions per plant after 3 weeks. Differences in EREB
      population levels did not explain the observed differences in host infection
      frequencies, and the results indicated that strain B24-B2 was reduced in its
      ability to infect the host via the hydathodes, but unaffected in infection via
      wounds. When strains B-24 and B24-B2 were mixed in equal numbers and sprayed on
      plants together, B24-B2 epiphytic populations were intermediate between those of
      B-24 applied alone and B24-B2 applied alone. These results indicate that a
      functional pigB is required for epiphytic survival and natural host infection
      under the experimental conditions tested, and suggest that DF, xanthomonadins,
      and EPS could all be important for survival of this pathogen on the leaf surface,
      and/or for host infection.

PMID- 9612946
TI  - The Bradyrhizobium japonicum noeD gene: a negatively acting, genotype-specific
      nodulation gene for soybean.
AB  - Bradyrhizobium japonicum strain USDA 110 is restricted for nodulation by soybean
      genotype PI 417566. We previously reported the identification of a USDA 110 Tn5
      mutant, strain D4.2-5, that had the ability to overcome nodulation restriction
      conditioned by PI 417566 (S. M. Lohrke, J. H. Orf, E. Martinez-Romero, and M. J.
      Sadowsky, Appl. Environ. Microbiol. 61:2378-2383, 1995). In this study, we report
      the cloning and characterization of the negatively acting DNA region mutated in
      strain D4.2-5 that is involved in the genotype-specific nodulation of soybean.
      The Tn5 integration site was localized to a 5.2-kb EcoRI fragment isolated from
      wild-type USDA 110 genomic DNA. Saturation Tn5 mutagenesis of this 5.2-kb region
      and DNA homogenitization studies indicated that a 0.9-kb DNA region was involved
      in the genotype-specific nodulation of PI 417566. A single open reading frame
      (ORF) of 474 nucleotides, encoding a predicted protein of 158 amino acids, was
      identified within this region by DNA sequencing. This ORF was named noeD.
      Computer comparisons with available data bases revealed no significant
      similarities between the noeD DNA or predicted amino acid sequence and any known
      genes or their products. However, comparisons done with the region upstream of
      noeD revealed a high degree of similarity (about 76% similarity and 62% identity)
      to the N-terminal regions of the Rhizobium leguminosarum bv. viciae and R.
      meliloti nodM genes, which have been postulated to encode a glucosamine synthase.
      Southern hybridization analysis indicated that noeD is not closely linked to the
      main or auxiliary nodulation gene clusters in B. japonicum and that both
      nodulation-restricted and -unrestricted B. japonicum serogroup 110 strains
      contain a noeD homolog. High-performance liquid chromatography and fast atom
      bombardment-mass spectrometry analyses of the lipo-chitin oligosaccharide (LCO)
      nodulation signals produced by an noeD mutant showed a higher level of
      acetylation than that found with wild-type USDA 110. These results suggest that
      specific LCO signal molecules may be one of the factors influencing nodulation
      specificity in this symbiotic system.

PMID- 9612947
TI  - Suppression of tobacco basic chitinase gene expression in response to
      colonization by the arbuscular mycorrhizal fungus Glomus intraradices.
AB  - A differentially displayed cDNA clone (MD17) was isolated from tobacco roots
      (nicotiana tabacum cv. Xanthi-nc) infected with the arbuscular mycorrhizal (AM)
      fungus Glomus intraradices. The isolated DNA fragment exhibited a reduced level
      of expression in response to AM establishment and 90% identity with the 3'
      noncoding sequence of two basic chitinases (EC 3.2.1.14) from N. tabacum.
      Northern (RNA) blots and Western blots (immunoblots), probed with tobacco basic
      chitinase gene-specific probe and polyclonal antibodies raised against the
      chitinase enzyme, yielded hybridization patterns similar to those of MD17.
      Moreover, the up-regulation of the 32-kDa basic chitinase gene expression in
      tobacco roots by (1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester (BTH) was
      less effective in mycorrhizal roots than in nonmycorrhizal controls. Suppression
      of endogenous basic chitinase (32-kDa) expression was also observed in transgenic
      mycorrhizal plants that constitutively express the 34-kDa basic chitinase A
      isoform. When plants were grown with an increased phosphate supply, no
      suppression of the 32-kDa basic chitinase was obtained. These findings indicate
      that during the colonization and establishment of G. intraradices in tobacco
      roots, expression of the basic chitinase gene is down-regulated at the mRNA
      level.

PMID- 9612948
TI  - Tm-2(2) resistance in tomato requires recognition of the carboxy terminus of the
      movement protein of tomato mosaic virus.
AB  - The Tm-2(2) resistance gene is used in most commercial tomato cultivars for
      protection against infection with tomato mosaic virus (ToMV). It has been
      suggested that Tm-2(2) resistance interferes with viral cell-to-cell movement in
      plants; ToMV strain ToMV-2(2) requires two amino acid (aa) exchanges in the
      carboxy-terminal region of the viral 30-kDa movement protein (at positions 238
      and 244) to overcome Tm-2(2) resistance. For further analysis of this region of
      the 30-kDa protein, two stop codons were introduced into ToMV movement proteins
      at aa positions 235 and 237, leading to deletion of the terminal 30 aa. The
      mutant virus strains were able to infect wild-type tomato plants systemically,
      suggesting the carboxy-terminal portion of the ToMV 30-kDa protein is dispensable
      for virus transport in tomato. Even more important, the deletion mutants overcame
      the Tm-2(2) resistance gene. These data indicate the carboxy-terminal domain of
      the ToMV movement protein serves as a recognition target in the context of the Tm
      2(2) resistance gene. Furthermore, expression of the 30-kDa movement protein from
      wild-type ToMV, but not from ToMV-2(2), in transgenic tomato plants with the Tm
      2(2) resistance gene led to elicitation of a necrotic reaction in tomato
      seedlings, showing that the 30-kDa protein on its own is able to induce the
      plant's defense reaction.

PMID- 9612949
TI  - The Medicago truncatula MtAnn1 gene encoding an annexin is induced by Nod factors
      and during the symbiotic interaction with Rhizobium meliloti.
AB  - Here we report the characterization of a new Nod factor-induced gene from
      Medicago truncatula identified by mRNA differential display. This gene,
      designated MtAnn1, encodes a protein homologous to the annexin family of calcium-
      and phospholipid-binding proteins. We further show that the MtAnn1 gene is also
      induced during symbiotic associations with Rhizobium meliloti, both at early
      stages in bacterial-inoculated roots and in nodule structures. By in situ
      hybridization, we demonstrate that MtAnn1 expression in nodules is mainly
      associated with the distal region of invasion zone II not containing infection
      threads, revealing MtAnn1 as a new marker gene of the pre-infection zone.
      Moreover, analyses of MtAnn1 expression in response to bacterial symbiotic
      mutants suggest that the expression of MtAnn1 during nodulation requires
      biologically active Nod factors and is independent of the infection process.

PMID- 9612950
TI  - Differential induction of the Arabidopsis thaliana Thi2.1 gene by Fusarium
      oxysporum f. sp. matthiolae.
AB  - The Arabidopsis thaliana Thi2.1 gene is inducible by necrotrophic fungi through a
      signal transduction pathway different from that for pathogenesis-related (PR)
      proteins. We have identified three ecotypes that are susceptible (Col-2, Ler, and
      Ws) and two ecotypes that are resistant (Mt-0 and Uk-4) to spray inoculation with
      Fusarium oxysporum f. sp. matthiolae. The Thi2.1 transcript level after infection
      correlates with resistance, being 5 to 10 times higher in the resistant than in
      the susceptible ecotypes. The beta-glucuronidase (GUS) expression of a Thi2.1
      promoter-uidA fusion (with a promoter derived from Col-2) is on the average
      almost 10 times higher in the Uk-4 background than in the Col-2 background. This
      confirms the results obtained by Northern (RNA) blots and indicates that Uk-4,
      and probably other resistant ecotypes too, might have a more sensitive
      recognition system for F. oxysporum f. sp. matthiolae or might have a signal
      transduction system that gives a higher amplification of the original recognition
      signal. Our results suggest a role of the Thi2.1 gene in resistance against F.
      oxysporum f. sp. matthiolae and perhaps other necrotrophic fungi.

PMID- 9612951
TI  - Expression of a defense-related 3-hydroxy-3-methylglutaryl CoA reductase gene in
      response to parasitization by Orobanche spp.
AB  - Orobanche spp. are angiosperms that live parasitically on the roots of other
      plants, and are capable of significantly reducing the yield and quality of their
      crop hosts. We have demonstrated that parasitization by Orobanche induces
      expression of hmg2, a defense-related isogene of 3-hydroxy-3-methylglutaryl CoA
      reductase (HMGR) in tobacco. Transgenic tobacco plants expressing a construct
      containing 2.3 kb of the tomato hmg2 gene promoter fused to the beta
      glucuronidase (GUS) reporter gene were parasitized by O. aegyptiaca. Expression
      of the hmg2:GUS construct was detected within 1 day following penetration of the
      host root by the O. aegyptiaca radicle and was localized to the region
      immediately around the site of parasite invasion. This expression continued and
      intensified over the course of O. aegyptiaca development. In addition, the
      hmg2:GUS expression was induced by secondary parasitization, where secondary
      roots of O. aegyptiaca contacted the host root at a distance from the primary
      attachment site. This GUS expression was specific to plants containing the
      hmg2:GUS construct, and was not observed in control plants transformed with a
      construct of the cauliflower mosaic virus 35S promoter fused to the GUS gene.
      These results indicate that Orobanche parasitization initiates rapid and
      sustained induction of a defense-related gene in the host root.

PMID- 9612952
TI  - Entry of Xanthomonas campestris pv. campestris into hydathodes of Arabidopsis
      thaliana leaves: a system for studying early infection events in bacterial
      pathogenesis.
AB  - Xanthomonas campestris pv. campestris (Xcc) is a vascular pathogen of cruciferous
      plants that normally gains entry to plants via hydathodes. In order to study the
      basis of the preference for this protal of entry we have developed an Arabidopsis
      thaliana model with attached or detached leaves partially immersed in a bacterial
      suspension. Entry of bacteria into leaves, assessed by resistance to surface
      sterilization, could be detected after 1 h. Dissection of leaves and
      histochemical staining for beta-glucuronidase produced by the bacteria indicated
      that they were located in hydathodes. In contrast, similar experiments with the
      leaf-spotting pathogen X. campestris pv. armoraciae gave patterns of localized
      staining dispersed over the leaf area, indicative of entry through stomata. A
      survey of 41 A. thaliana accessions showed that they fell into three classes
      distinguishable by total numbers of Xcc that entered under standard conditions
      and by preference for hydathode colonization. Previously isolated Xcc mutants
      affected in pathogenicity were tested for hydathode colonization: an hrp mutant
      behaved indistinguishably from the wild type, and rpf regulatory mutants gave 10
      fold reduced colonization, whereas with rfaX mutants with altered
      lipopolysaccharide, few if any viable bacteria were recoverable from hydathodes.
      This fact, together with the rapid induction of superoxide dismutase in the
      bacteria located in hydathodes, suggests that an early defense reaction is
      mounted in the hydathode.

PMID- 9612953
TI  - Activation of hsr203, a plant gene expressed during incompatible plant-pathogen
      interactions, is correlated with programmed cell death.
AB  - hsr203J is a tobacco gene whose activation is rapid, highly localized, and
      specific for incompatible interactions between tobacco and the bacterial pathogen
      Ralstonia solanacearum. The effect of other hypersensitive response (HR)-inducing
      pathogens and elicitors has been tested with transgenic plants containing the
      hsr203J promoter-GUS reporter gene fusion, and confirms the generality of the
      preferential inducibility of the hsr203J gene promoter during incompatible
      interactions: bacterial and viral pathogens inducing an HR in tobacco were able
      to induce the promoter fusion, as were inducers of HR-like responses such as
      harpin, elicitins, and PopA1 proteins. A tomato hsr203 homologous cDNA was
      isolated (Lehsr203) and used to examine the effect of avr gene products on the
      expression of such genes. Lehsr203 was shown to be rapidly and transiently
      induced in leaves of the tomato Cf-9 line, following Avr9 product infiltration,
      but not in those of the Cf-0 line. Among potential effectors of HR or resistance
      such as H2O2, salicylic acid, methyl jasmonate, and 2,6-dichloro-isonicotinic
      acid (INA), none is able to induce a significant increase in promoter activation.
      In contrast, heavy metals that cause leaf necrosis can trigger such an
      activation. In addition, hsr203-GUS fusion expression is detected in transgenic
      tobacco lines expressing the bO gene and exhibiting spontaneous HR-like lesions.
      Taken together, these results demonstrate a strong correlation between hsr203 and
      genetically controlled cell death in tobacco and tomato. The expression of this
      gene should be a useful marker for programmed cell death occurring in response
      not only to diverse pathogens, but also to diverse death-triggering extracellular
      agents.

PMID- 9612954
TI  - The hrpC and hrpN operons of Erwinia chrysanthemi EC16 are flanked by plcA and
      homologs of hemolysin/adhesin genes and accompanying activator/transporter genes.
AB  - The hrpC operon of Erwinia chrysanthemi EC16 encodes five genes conserved in
      Erwinia amylovora and Pseudomonas syringae. Mutagenesis indicated that hrcC is
      required for elicitation of the hypersensitive reaction in tobacco leaves. The
      unexpected presence of plcA and homologs of hemolysin/activator genes in the
      regions flanking the hrcC and hrpN operons is reported.

PMID- 9612955
TI  - The myristylation motif of Pto is not required for disease resistance.
AB  - The tomato Pto kinase confers resistance to bacterial speck disease caused by
      strains of Pseudomonas syringae pv. tomato that express the avirulence gene
      avrPto. Pto contains a putative myristylation site at its amino terminus that was
      hypothesized to play a role in localizing Pto in the plant cell. Site-directed
      mutagenesis was used to change the invariant glycine residue in the myristylation
      motif to an alanine. Transgenes encoding the mutant Pto(G2A) and wild-type Pto
      were placed behind the cauliflower mosaic virus 35S promoter and transformed into
      tomato plants that are susceptible to bacterial speck disease. Both the mutant
      and wild-type forms of Pto conferred resistance to a strain of P. syringae pv.
      tomato expressing avrPto. These results indicate that the myristylation motif of
      Pto is not required for bacterial speck disease resistance.

PMID- 9612957
TI  - An antiviral protein from Bougainvillea spectabilis roots; purification and
      characterisation.
AB  - An antiviral protein active against mechanical transmission of tomato spotted
      wilt virus was identified in the root tissues of Bougainvillea spectabilis Willd.
      Bougainvillea Antiviral Protein I (BAP I) was purified to apparent homogeneity
      from the roots of Bougainvillea by ammonium sulphate precipitation, CM- and DEAE
      Sepharose chromatography and reverse phase HPLC. BAP I is a highly basic protein
      (pI value > 8.6) with an Mr of 28,000. The N-terminal sequence of BAP I showed
      homology with other plant antiviral proteins. Preliminary tests suggest that
      purified BAP I is capable of interfering with in vitro protein synthesis.

PMID- 9612956
TI  - A probarley lectin processing enzyme purified from Arabidopsis thaliana seeds.
AB  - An aspartic proteinase was purified from the seeds of Arabidopsis thaliana
      (ecotype RLD) using affinity chromatography on pepstatin-agarose and ion exchange
      chromatography. The purified enzyme is optimally active at pH 3.5 and completely
      inhibited by pepstatin A. The purified Arabidopsis aspartic proteinase contains
      four subunits (apparent molecular weights 31, 28.5, 15 and 6 kDa), two of which
      are probably linked by disulfide bridges. These properties are similar to the
      aspartic proteinase previously isolated from barley seeds. The amino acid
      sequence of the peptide subunits corresponds exactly with the sequence of the
      previously isolated cDNA for the Arabidopsis aspartic proteinase. The Arabidopsis
      enzyme processed probarley lectin in vitro at the carboxy-terminus between
      phenylalanine and alanine, the same place where the barley enzyme cleaves the
      lectin in vitro. The aspartic proteinase appears to be the major enzyme
      processing the lectin in seeds as pepstatin A inhibited this activity in a crude
      seed extract.

PMID- 9612958
TI  - A tannin anti-cancer promotor from Terminalia arjuna.
AB  - A new ellagitannin named; arjunin, four known tannins and two phenolic acids were
      isolated from Terminalia arjuna. The structures were elucidated by spectroscopic
      analyses.

PMID- 9612959
TI  - Xanthones from the twigs of Mammea siamensis.
AB  - 1,2-Dimethoxy-5-hydroxyxanthone, a new xanthone, was isolated from the twigs of
      Mammea siamensis, in addition to six known xanthones (5-hydroxy-1-methoxy-, 1,3
      dimethoxy-5-hydroxy-, 2,5-dihydroxy-1-methoxy-, 1,7-dihydroxy-, 1,3,7-trihydroxy-
      and 3,5-dihydroxy-1-methoxyxanthone). Structures for these compounds were deduced
      from their spectral data.

PMID- 9612960
TI  - [Principles of intensive and anesthesiologic care in gunshot injuries].

PMID- 9612961
TI  - [Objective assessment of the severity of gunshot wounds].
AB  - By the present time, many mathematical models have been developed for assessing
      the status of patients with grave mechanical injuries. However, comparative
      analysis of the efficacy of predicting the outcomes of shock and traumatic
      disease with the use of some models in patients with war and other than war
      traumas showed that these methods are not fit for cases with gunshot wounds. We
      consider that a differentiated approach is needed in assessment of the status of
      wounded and injured patients.

PMID- 9612962
TI  - [Intensive care of patients injured by mine explosions].

PMID- 9612963
TI  - [Anticipated intensive care in gunshot injuries of the abdomen].
AB  - Analysis of intensive care of 345 patients with gunshot wounds permitted the
      development of standard protocols of such care with consideration for the
      visceral injuries. In wounds to the large intestine, multiple-modality treatment
      including hyperbaric oxygenation, extracorporeal detoxication, and intraaortic
      infusion of drugs is recommended irrespective of the phase of peritonitis. In
      injuries to the small intestine, traditional intensive care (infusion therapy,
      partial parenteral nutrition, prolonged epidural blocking, and antibiotics) can
      be sufficient. However, in both cases these methods are to be used not after
      manifestation of signs of disorders in the abdominal cavity, but anticipate them,
      and the treatment is to be based on the general regularities in the course of
      traumatic disease in wounded patients. Such an approach can prevent the progress
      of peritonitis and improve the outcome of wound.

PMID- 9612964
TI  - [Artificial ventilation of lungs in wounded patients and patients with severe
      mechanical injuries].
AB  - Artificial ventilation of the lungs with positive pressure at the end of
      respiration and inverse ratio of the respiratory phases was used in patients with
      wounds and grave mechanical injuries involving acute injuries to the lungs.
      Negative effect of positive pressure at the end of respiration on gas exchange,
      hemodynamics, and biomechanics of the lungs was confirmed and therefore this
      method is not recommended for such patients. Artificial ventilation of the lungs
      with inverse ratio of the respiratory phases improved gas exchange and
      biomechanical properties of the lungs, reduced the negative effect of forced
      ventilation on hemodynamics, and decreased the incidence of complications.

PMID- 9612965
TI  - [Multiple organ failure syndrome in critically ill patients].
AB  - A new approach to defining the notion of multiple organ failure is proposed. It
      is based on division of the organ humoral injuries at the stages of dysfunction,
      insufficiency, and failure. Criteria of these stages are defined for the central
      nervous and cardiovascular systems, lungs, liver, kidneys, and gastrointestinal
      tract.

PMID- 9612966
TI  - [Classification of acute dysfunctions of organs and systems in multiple organ
      failure syndrome].
AB  - A classification of acute dysfunctions of the vital organs and systems in cases
      with multiple organ failure is proposed. It is suggested to assess the function
      as satisfactory, compensatory sufficiency, decompensated insufficiency, or
      failure. Clinical laboratory criteria of such rating are offered. Experience
      gained in the use of this classification is presented.

PMID- 9612967
TI  - [General biological characteristics of the etiology of postoperative
      complications in patients with surgical diseases of the lungs].
AB  - The causes of lethal outcomes (n = 60) and postoperative complications which
      occurred in 26.1% of 610 patients operated on for lung cancer were investigated
      with due consideration for the regularities of thermodynamics of nonequilibrium
      processes and theory of disasters. A total systems pathological inflammatory
      reaction, which augments the injury by many times and develops as a result of
      inadequate anesthesiological protection, underlies the development of the most
      unfavorable variant of response to surgery leading to life-threatening
      complications, such as pneumonia, thromboembolism, or ulcerative hemorrhages.

PMID- 9612968
TI  - [Nature of centrogenic reactions developing during surgical interventions on the
      brain].
AB  - The nature of hemodynamic reactions and EEG changes developing during surgery is
      discussed, based on analysis of 392 interventions for removal of brain tumors.
      Two main types of centrogenic reactions are distinguished: (1) connected with the
      direct effect on brain centers engaged in cardiovascular regulation and (2)
      caused by stimulation of the median structures of the brain, most often caused by
      hyperperfusion in different compartments of the brain. Use of anesthesiological
      method limiting the functional relations between the brain stem and forebrain
      notably decreases the incidence of centrogenic reactions during neurosurgical
      interventions.

PMID- 9612969
TI  - [Effects of several methods of general anesthesia on the cerebral blood flow and
      cerebrovascular reactivity: transcranial dopplerography data].
AB  - Effects of some methods of total anesthesia on the cerebral bloodflow and
      cerebrovascular reactivity was studied by transcranial dopplerography. Ketamine
      appreciably increases the cerebral bloodflow if no benzodiazepines are injected
      simultaneously. In patients with intracranial abnormalities ketamine can increase
      intracranial hypertension and disorder the cerebral perfusion. Despite the
      manifest hypotensive effect of diprivan, the autoregulation reserve of the
      cerebral bloodflow is not changed, probably due to the indirect vasoconstrictive
      effect of the drug. Total anesthesia with N2O and fentanyl virtually does not
      influence brain circulation.

PMID- 9612970
TI  - [Relationship between indicators of systemic and cerebral hemodynamics during
      anesthesia in patients with voluminous formations in the brain].
AB  - Relationship between total systems and cerebral (assessed by dopplerography)
      hemodynamics was studied in patients with bulky formations of the brain during
      total anesthesia. The hemodynamic type of circulation and the direction of
      hemodynamic reactions during surgery and anesthesia corresponded to the
      preoperative values. The hypokinetic type of circulation in such patients, who
      are to be operated on in the lying posture, and alteration of the circulation
      type during the preoperative head-down tilt in the patients to be operated on in
      the sitting posture refers them to a group at a high risk of postoperative
      complications.

PMID- 9612971
TI  - [Main types of electroencephalographic reactions in neurologic patients under
      intensive care and hyperbaric oxygenation therapy].
AB  - Bioelectrical activity of the brain was monitored by EEG during exposure to
      hyperbaric oxygenation (5 check-ups per session), which was a component of
      intensive care of neurological patients. The data obtained in the course of 395
      sessions in 182 patients helped distinguish four types of reactions of such
      patients to hyperbaric oxygenation. Analysis of these data and the results of
      clinical examinations discloses the functional significance of these types and
      helps more objectively define the indications for further application of this
      treatment modality.

PMID- 9612972
TI  - [Antihypoxants in emergency medicine].
AB  - Presents the results of many-year experimental studies, clinical trials, and
      medical use of drugs of a new pharmacological class: antihypoxants. Antihypoxants
      are perspective drugs of urgent medicine, which was demonstrated on various
      models (all types of hypoxia, myocardial, brain, renal, and liver ischemia, grave
      mechanical and thermal injuries, blood loss, etc.) and in patients with these
      states.

PMID- 9612973
TI  - [Use of antihypoxants in the acute period of myocardial infarction].
AB  - A total of 620 patients with acute myocardial infarction were followed up in
      order to assess the efficacy of antihypoxants as a component of intensive care.
      385 of these patients, divided into groups of 20-40 subjects, were administered
      one of 12 antihypoxants or sessions of hyperbaric oxygenation during the acute
      period of the disease, the rest were treated traditionally. Analysis of clinical,
      laboratory, and prognostic values showed the highest protective effect of
      amtizol, lithium hydroxybutyrate, piracetam, and ubiquinone. Cytochrome C,
      riboxine, mildronate, and olifen were somewhat less active, and solcoseryl,
      bemitil, trimethasidine, and aspisol were the least effective. The protective
      potentialities of standard sessions of hyperbaric oxygenation were virtually
      null. The author proposes a parameter D, reflecting the difference between actual
      and predicted mortality, and the rating (score) system for assessing the routine
      laboratory diagnostic tests to be used together with the known criteria for
      evaluation of the protective effects of antihypoxants in patients with acute
      myocardial infarction.

PMID- 9612974
TI  - [Intravenous anesthesia in surgical interventions in ambulatory practice].
AB  - Intravenous anesthesia with calipsol and diprivan was used in 297 gynecological
      patients subjected to various short-term interventions. The course of anesthesia
      was monitored (arterial pressure, respiration rate, SaO2, Fet CO2) and time
      course of recovery of attention, thinking, and motor activity in the
      postoperative period after different types of anesthesia was assessed. Diprivan
      and fentanyl (0.7-0.8 microgram/kg) anesthesia is preferable for surgical
      interventions in an outpatient setting due to a smooth and uneventful course of
      the postoperative period and its slight effect on the cardiovascular system.

PMID- 9612976
TI  - [Prevention of post-puncture headache after surgical interventions with spinal
      anesthesia].

PMID- 9612975
TI  - [Anesthesiological provisions in ambulatory dentistry].
AB  - Ten methods of intravenous anesthesia for dental treatment were used in 6504
      patients in an outpatient setting. Drug doses were assessed in 504 patients and
      complications caused by anesthesia analyzed. Intravenous anesthesia with
      combinations of diprivan, diazepam (relanium), calipsol, and tramal is
      preferable. The most prevalent complication of anesthesia which requires special
      treatment is aseptic postinjection phlebitis, most incident after sombrevin.

PMID- 9612977
TI  - [Standards of anesthesiological and intensive care].

PMID- 9612978
TI  - [Standards of examination, anesthesia and postoperative care of surgical patients
      with concomitant cardiovascular diseases].
AB  - The authors present the standards for postoperative care of patients with
      concomitant cardiovascular diseases used at Medical Center No. 122 in St.
      Petersburg. Special attention is paid to detailed assessment of cardiac function,
      continuity of the pre-, intra-, and postoperative cardio- and vasotropic therapy,
      and adequacy of anesthesiological protection as the main guarantee of an
      uneventful postoperative course. The authors consider it important that
      preoperative examinations include echocardiography and daily ECG monitoring;
      preoperative treatment is to include antibiotic prevention of infective
      endocarditis and heparin prevention of pulmonary artery embolism in the risk
      group patients. Alternative methods for intraoperative hemodynamic monitoring are
      pulmonary artery catheterization and integral rheography with the real-time data
      processing. The importance of regional anesthesia and the hazards of
      hypercorrection of the globular volume are emphasized.

PMID- 9612979
TI  - [Causes and prevention of sudden arrest of circulation in surgical treatment of
      rheumatic mitral defect].
AB  - Analysis of case histories of patients operated on in 1965-1995 is presented.
      Ventricular fibrillation or asystole was observed in 3.34e 1.1% of 480 patients
      subjected to closed mitral commissurotomy and in 6.25e 1.1% of 98 ones subjected
      to cardiopulmonary bypass surgery for replacing mitral valves. The incidence of
      complications directly correlated with the stage of mitral valvular disease and
      reoperations and inversely with monitoring of hemodynamics, blood gases, etc.
      Examination of the myocardium before the development of ventricular fibrillation
      or asystole most often revealed 1) myocardial ischemia of different degree and
      localization; 2) changed stimulation and conduction of the myocardium; 3) total
      myocardial hypoxia; 4) electric current action in cases with diathermal
      coagulation of vessels and/or poor grounding of devices; 5) injection of potent
      drugs, etc. Electromechanical dissociation of ventricular myocardium was observed
      in 6 patients. Sudden heart arrest was not caused by blocking of the bloodflow in
      any of the cases. Thus, some signs can be regarded as predicting the risk of
      sudden arrest of circulation. Monitoring of the functions of the body helps
      timely detect these signs. If ventricular fibrillation developed, defibrillation
      was carried out immediately.

PMID- 9612980
TI  - A volumetric study of guided bone regeneration around titanium implants in the
      New Zealand white rabbit.
AB  - Previous studies have shown the ability for bone to grow under occlusive
      membranes. This study was undertaken to determine the time required for bone to
      form in the space created under the membrane and to determine the amount of bone
      that may be grown under the membrane. Thirty-two New Zealand white rabbits were
      divided into three groups. A Branemark implant, having a diameter of 3.75 mm with
      a length of 7 mm, was placed in each tibia and Gore-Tex membrane was draped over
      the implant on the experimental side and tethered to the wound margin. Sixteen
      rabbits were sacrificed at six weeks, eight at twelve weeks, and eight at
      eighteen weeks. At six weeks the available space under the membrane was filled to
      68 per cent, at twelve weeks it was 45 per cent, and at eighteen weeks 54 per
      cent. A comparison of bone height measurements on test and control sides showed a
      significant difference (p = 0.0001) at the three time intervals. A comparison of
      grown bone volumes (test vs control) was also statistically significant (p =
      0.0001). The ability to grow bone under an occlusive membrane was confirmed but
      the long-term survival rate and ability to support load needs to be investigated.

PMID- 9612982
TI  - Molecular biological techniques and their use to study streptococci in dental
      caries.
AB  - This review explains some of the basic techniques of molecular biology and their
      application to the study of oral streptococci. Examples of how these techniques
      have furthered the understanding of streptococcal colonization in health and
      disease are discussed along with approaches to controlling dental caries that
      have been made plausible by the knowledge gained using these techniques.

PMID- 9612981
TI  - Shear bond strength of chemical and light-cured glass ionomer cements bonded to
      resin composites.
AB  - A bond between glass ionomer cements (GIC) and resin composites is desirable for
      the success of the 'sandwich' restoration. Chemically cured glass ionomer cements
      have been the traditional materials used in this technique since its development,
      but etching the GIC was necessary to obtain a bond to the composite facing.
      Producing a very smooth GIC surface has aided in better determining the magnitude
      of the chemical bond between glass ionomers and resin composites. Shear testing
      of bonded specimens has revealed that chemical bonding is minimal (0.21 MPa) in
      conventional glass ionomers, but does exist (4.92 MPa) between GIC and resin
      composite regardless of the filler content (microfilled vs hybrid) of the
      composite. Thermal stressing affects the bond to resin-modified glass ionomers,
      but has no significant effect on self-cured cements. Of all combinations tested.
      Vitremer/Scotchbond/Silux Plus showed the highest mean shear bond strength. Based
      on the clinical need for an adhesive bond between GIC liner/base and resin
      composite, the resin-modified glass ionomer would appear to be the material of
      choice.

PMID- 9612983
TI  - Purification and characterization of a putative fimbrial protein/receptor of
      Porphyromonas gingivalis.
AB  - Porphyromonas gingivalis has been implicated as a major aetiological agent in
      certain forms of periodontal disease, P. gingivalis is a Gram-negative,
      asaccharolytic bacterium that obtains energy from the fermentation of amino acids
      derived from the hydrolysis of host protein. Virulence factors of this bacterium
      include the capsule, fimbrial adhesins, cytotoxins and extracellular hydrolytic
      enzymes. A 43 kDa fimbrillin from P. gingivalis has been isolated and
      characterized. However, there is evidence that a second type of fimbria exists on
      the surface of P. gingivalis. A putative P. gingivalis fimbrial protein from a
      membrane preparation has been isolated and identified. This protein was shown to
      be reactive with sera from patients harbouring P. gingivalis. A 28 kDa protein
      fragment was purified by anion exchange, gel filtration and reversed-phase
      chromatography. N-terminal sequence analysis of the 28 kDa protein fragment
      revealed homology to the fimbrial precursor protein of Dichelobacter nodosus. A
      peptide corresponding to the N-terminal 26 amino acyl residues of the 28 kDa
      protein fragment was synthesized and used to raise antibodies to the protein.
      Western blot analysis after SDS-PAGE of a P. gingivalis membrane preparation
      using the antibodies raised to the synthetic peptide detected three proteins of
      36, 41 and 67 kDa. When protease inhibitors were not included in the extraction
      procedure only the 36 and 41 kDa bands were detected. It would appear, therefore,
      that the intact protein has an M(r) of 67 kDa and that the 28, 36 and 41 kDa
      bands represent protein fragments produced by endogenous proteolytic activity.
      Based on sequence homology, the 67 kDa protein is possibly a sub-unit of a second
      P. gingivalis fimbrial type or a surface receptor.

PMID- 9612984
TI  - Studies on fusobacteria associated with periodontal diseases.
AB  - The physiological and metabolic characteristics of representative isolates of the
      various subspecies of Fusobacterium nucleatum were investigated by growing them
      in continuous culture in chemically-defined, media. Behaving almost identically,
      these organisms were found to obtain energy from the fermentation of simple
      carbohydrates such as glucose or fructose or from the fermentation of certain
      amino acids, free or in the form of small peptides. The latter can be attacked by
      aminopeptidase activity which was shown to be essential for the growth of the
      organism in an environment lacking fermentable carbohydrate and free amino acids
      but replete with small peptides. This metabolic versatility may explain the
      presence of F. nucleatum in both supra- and sub-gingival dental plaque and why it
      is often found together with organisms such as Porphyromonas gingivalis which
      display powerful endopeptidase activities. Using the technique of allozyme
      electrophoresis, the current subspeciation of F. nucleatum was shown to be of
      doubtful validity and evidence, based upon physiological and metabolic
      properties, for differences in pathogenicity between isolates was not detected.
      While this organism is a member of various bacterial consortia associated with
      periodontal diseases, its contribution to the disease process remains unclear.

PMID- 9612985
TI  - Enamel cracks. The role of enamel lamellae in caries initiation.
AB  - Lamellae or cracks are distributed throughout tooth enamel in both deciduous and
      permanent dentitions. While earlier authors postulated that lamellae may be
      pathways of entry for caries, no evidence was adduced and the theory appears to
      have been discounted. The present study seeks to show that, at least in some
      cases, lamellae are permeable to dyes, may be associated with caries initiated in
      the dentine, supporting the hypothesis of Hardwick and Manly of lamellae
      penetration by Streptococcus mutans and lactobacilli. The enamel lamellae are
      shown to be a permeable pathway allowing caries-producing bacteria access to the
      dentine-enamel junction. Caries can thus be established within the tooth without
      visible evidence at the surface.

PMID- 9612986
TI  - Dental erosion and bruxism. A tooth wear analysis from south east Queensland.
AB  - Tooth-tissue loss from erosion and attrition from bruxism were associated
      findings in 104 patients with excessive toothwear from South East Queensland.
      Approximately one-third of these subjects had been given a diagnosis of bruxism
      prior to referral. After a structured interview and clinical examination, the
      prevailing diagnosis was tooth erosion associated with occupational or sports
      related dehydration, and one-third of the subjects were provisionally classified
      as bruxers. Eight items of clinical history and examination, designed to
      differentiate bruxers from non-bruxers, were analysed retrospectively from their
      records. These clinical items, by which the diagnosis of bruxism might be made,
      segregated the subjects into three groups of equal size, 'bruxers, possible
      bruxers and non-bruxers,' by a notional score for bruxism. The presence of
      occlusal attrition or erosion on the sextants of the dentitions was determined by
      scanning electron microscopic criteria on epoxy resin dental casts. The incidence
      of attrition versus erosion was compared between the three groups. The hypothesis
      was that attrition would be found on more sextants of bruxers than non-bruxers.
      Erosion predominated in virtually all sextants in all three groups, to the
      virtual exclusion of attrition in the molar sextants. The exception was the
      mandibular anterior sextant, where more sextants in bruxers were affected by
      attrition. Thus extrinsic or intrinsic acid erosion was strongly associated with
      occlusal tooth wear found in bruxers. Conversely, tooth-wear patterns were
      unreliable indicators of a bruxing habit, for attrition alone was often found on
      acid-exposed teeth. Thus, even if a patient is suspected of having bruxism,
      dental erosion is more likely the cause of tooth-tissue loss than attrition,
      especially in the dehydrating environment of South East Queensland.

PMID- 9612988
TI  - The way it is.

PMID- 9612987
TI  - ADRF Trebitsch Scholarship. The microbial contamination of toothbrushes. A pilot
      study.
AB  - Ten individuals were each supplied with a new toothbrush of the same type and
      brand, together with identical tubes of fluoridated toothpaste. After a three
      week period, during which subjects were asked to follow their usual oral hygiene
      practices, the toothbrushes were collected and assayed for microbial
      contamination using a range of selective growth media. The total microbial load
      per toothbrush was found to be 10(4) to 10(5) colony forming units. Staphylococci
      were found on all toothbrushes and streptococci on all but one. These two genera
      were also quantitatively dominant. Candida, corynebacteria, pseudomonads and
      coliforms were identified in 70, 60, 50 and 30 per cent of toothbrushes,
      respectively. However, mutans streptococci, lactobacilli and black-pigmented Gram
      negative anaerobic rods were not detected on any of the toothbrushes. For each
      individual, information on variables such as toothbrush rinsing practices and
      post-brushing storage methods and environment was collected. No obvious
      relationship between such variables and microbial load was apparent but it is
      suggested that more extensive studies are needed, taking into account additional
      parameters such as age and degree of toothbrush wear and the use of pre-brushing
      mouthwashes.

PMID- 9612989
TI  - Tooth decay, dietary changes and disease.

PMID- 9612990
TI  - Avulsion and rubber dam.

PMID- 9612991
TI  - What will the future hold?

PMID- 9612992
TI  - Baby friendly hospital initiative. For happier mothers and babies.

PMID- 9612993
TI  - Treatment for insect sting.

PMID- 9612994
TI  - The definition of 'pressure dressing'.

PMID- 9612995
TI  - Catfish and stingrays: hot water is first aid.

PMID- 9612996
TI  - Bullrout stings.

PMID- 9612997
TI  - Heroin addiction and naltrexone.

PMID- 9612998
TI  - Recent advances in contraception.
AB  - BACKGROUND: Advice regarding contraception, the means of fertility regulation for
      millions of women, is part of a general practitioner's bread and butter work. The
      area is however, developing at a rapid pace with the refinement of hormonal
      methods and the development of new and easier modes of delivery. OBJECTIVE: This
      article will review the results of recent studies in the area of reproductive
      health that better clarify the critical issues in the prescription and use of
      contraceptives. It will also describe contraceptive products that will soon be
      available in Australia. DISCUSSION: General practitioners need to convey the
      results of this research to patients so that they may make informed contraceptive
      choices based on evidence. Patients should also be made aware of all of their
      contraceptive options as well as the availability of emergency contraceptives.

PMID- 9612999
TI  - A comprehensive approach to premenstrual complaints.
AB  - BACKGROUND: General practice is characterised by its person-centred approach. It
      crosses the boundaries of all the medical disciplines as well as the boundary
      between medical and social problems. Family physicians are committed to dealing
      with whatever problem the patient presents. This is particularly relevant when
      women present with premenstrual complaints, since most do not have PMS as defined
      by researchers. Many have problems external to the menstrual cycle contributing
      to symptoms. Detection of these external factors, be they intercurrent medical,
      psychiatric or social problems, frequently determines treatment. OBJECTIVE: To
      describe a simple model of premenstrual complaints which includes all women who
      present in this way, in order ot inform GPs of the common patterns of illness in
      this group and provide them with a systematic approach to management. DISCUSSION:
      The model contains up to four levels of activity which may contribute to the
      complaint. These are: 1. menstrual cycle physiology--resulting in cyclical
      changes in mood, breast and bloating 2. intercurrent pathology (comorbidity)-
      gynaecological, psychiatric and medical 3. the social context of marital, family
      and work relationships, cultural influences 4. interpretation (attribution)--the
      meaning attached to the experience of the first 3 factors.

PMID- 9613000
TI  - Pathogenesis and treatment of genital candidiasis.
AB  - BACKGROUND: Genital candidiasis is the most common gynaecological infection and
      has the potential to produce considerable long-term sequelae especially with
      regard to sexual health. OBJECTIVE: The implications of the relatively higher
      levels of oestrogen found in women with genital candidiasis will be explored with
      particular regard to management of the infection. DISCUSSION: Genital candidiasis
      occurs commonly in otherwise healthy women with no identifiable predisposing
      factors other than oestrogen levels above those found in the proliferative phase
      of the ovarian cycle. Coming to an understanding of the pathophysiology of this
      clinical infection has important therapeutic implications.

PMID- 9613001
TI  - Dysfunctional uterine bleeding.
AB  - BACKGROUND: Dysfunctional uterine bleeding (DUB) affects about 5% of menstruating
      women. yet the majority of medical practitioners who manage the problem do not
      adequately understand the underlying pathophysiology nor the principles involved
      in appropriate management. OBJECTIVE: This article is an attempt to provide a
      brief overview of the problem and to review the current information regarding the
      diagnosis, incidence, cause and management of DUB. DISCUSSION: The majority of
      cases of DUB occur in the 5-10 years before the menopause or after the menarche,
      when the ovaries are in an unstable responsive state. Hormonal dysfunction is
      responsible for most cases of DUB and the condition will usually respond to
      appropriate hormonal therapy. In those instances where hormones are not a viable
      option or have not controlled the problem, then prostaglandin inhibitors or the
      use of tranexamic acid may allow short term relief from excessive bleeding.
      Surgery by endometrial ablation of hysterectomy should only be considered when
      all other options have failed.

PMID- 9613002
TI  - The management of the paediatric foreskin.
AB  - There are many conflicting opinions among health professionals and parents
      regarding care of the normal foreskin in young boys as well as the highly
      controversial subject of circumcision. Minor foreskin related complaints are very
      common in the first few years of life. Most of these can be managed with advice
      and reassurance, or with medical treatment alone. Circumcision is very rarely
      indicated in young boys, particularly under the age of 5 years. The issue of
      circumcision for non medical reasons, that is, religions, ethnic or personal,
      remains controversial.

PMID- 9613003
TI  - Searching the literature. A beginners' guide.
AB  - A number of questions will arise as you develop a research question. Has the
      question you are asking already been answered? Have other attempts been made to
      answer the question? If so, what techniques have been tried and what problems
      have arisen? Is there work in this area that will assist in developing your
      proposal? To find out you need to review the literature, that is, conduct a
      literature search. The idea of sitting in a medical library reading a few journal
      articles sounds interesting and easy. It is, but it is not a literature search.
      With so many medical journals published each year it is necessary to conduct a
      formal search of the published literature and the advent of electronic databases
      has simplified the process. However, there are a number of traps for beginners.
      As a beginner and having made most of the mistakes, I have been asked to write
      this article so that you can avoid the traps.

PMID- 9613004
TI  - Sporting and recreational injuries. In a general practice setting.
AB  - OBJECTIVE: To collect data on sporting and recreational injuries presenting to a
      general practice clinic in metropolitan Melbourne, to gain better knowledge about
      the range of these injuries commonly seen in general practice and in the
      community. METHOD: A survey was conducted for four, 2 week periods, at 3 monthly
      intervals, over approximately 1 year, at a general practice clinic in
      metropolitan Melbourne. All patients who presented with a new sporting or
      recreational injury were asked to complete a questionnaire, seeking information
      on the nature, circumstances, risk factors and severity of their injury, as well
      as why they had chosen to present to a general practice clinic, in preference to
      a hospital emergency department. It was completed by both the patient and the
      treating doctor. RESULTS: The main findings of the survey were that patients who
      presented to the clinic with a sporting or recreational injury were most likely
      to be male and in their twenties. The most common sports that had been played
      prior to injury were Australian rules football, soccer and hockey. The majority
      of injuries were relatively mild, with sprains and bruises accounting for 78% of
      injuries, while 89% of patients required conservative forms of treatment. The
      ankle, fingers and knee were the most common body parts affected. CONCLUSION:
      Data from general practice provides important information about the epidemiology
      of sporting and recreational injuries in the community.

PMID- 9613005
TI  - A week to remember.

PMID- 9613006
TI  - The six week postnatal check up. Should we forget it?
AB  - In order to deal with the uncertainty that is inherent. In general practice, many
      of us use accepted dogmas that we may have been taught as students, and which
      become incorporated into everyday practice in an unquestioning manner. How do
      some of these fare when held up to the light of current best practice and
      evidence based medicine? Some will hold true, others will go the way of many
      accepted best practices of the past; they fade into the annals of medicine as we
      move on to newer methods and techniques. This new series explores some of our
      current accepted practices or sacred cows.

PMID- 9613007
TI  - Emergency medicine. Is this a drug reaction?

PMID- 9613008
TI  - Radiology quiz. Suspected urinary calculus.

PMID- 9613009
TI  - Carpet layer's knee.

PMID- 9613010
TI  - Practice tip. A gamma radiation sterilised disposable theatre lamp handle.

PMID- 9613011
TI  - Looking toward retirement. The Janus complex.
AB  - What are the characteristics of a general practitioner and do they appear with
      time or are they inbred? What do GPs think of themselves and the professional
      life they have chosen? These questions and others should be answered as we follow
      the lives of different GPs at different stages of their professional lives. Each
      month we present the male and female perspective of the progressive evolution of
      the GP.

PMID- 9613012
TI  - Scleral icterus and fatigue. Part I.

PMID- 9613013
TI  - Are emotions frightening? II: An analogue study of fear of emotion, interpersonal
      conflict, and panic onset.
AB  - Two studies with college students were conducted to further explore the
      reliability and construct validity of fear of emotion, as assessed by the
      Affective Control Scale (ACS), a measure of fear of anxiety, depressed mood,
      anger, and strong positive emotion. The ACS fared well in tests of internal
      consistency and of convergent and divergent validity. In an analogue study of
      panic onset with college students with no history of panic, the predictive and
      incremental validity of the ACS was demonstrated: the ACS predicted students'
      fear of induced panic-like bodily sensations even once trait and state anxiety
      were statistically controlled. A second aspect of the investigation was an
      analogue test of the hypothesis that stress from interpersonal conflict (induced
      via remembrance of conflictual interactions with an important person) would
      moderate the ACS's effects on anxiety and fear of induced bodily sensations. This
      hypothesis was not confirmed.

PMID- 9613014
TI  - A clinical study of spider phobia: prediction of outcome after self-help and
      therapist-directed treatments.
AB  - The present clinical study was aimed at investigating predictors of treatment
      success, attrition and the extent of treatment needed to achieve clinically
      significant improvement in spider phobic patients. A total of 103 patients were
      included in the study after a detailed screening interview. There were four
      treatment conditions; self-help manual, video, group, and individual treatment,
      which the patients received in a hierarchical order providing they were not
      clinically significantly improved after the previous treatment. Pre and post each
      treatment the patients went through a behavioral approach test and filled in a
      number of self-report questionnaires. The results showed that 38 patients dropped
      out during the manual treatment, and 59 fulfilled the treatments to become
      clinically improved. The patients achieving clinical improvement after the two
      self-help treatments were significantly predicted, as was the extent of treatment
      needed. The significant predictors were credibility of the manual treatment and
      motivation for psychotherapy in general.

PMID- 9613015
TI  - Anxiety sensitivity: multiple dimensions and hierarchic structure.
AB  - Anxiety sensitivity (AS) is the fear of anxiety-related sensations, based on
      beliefs that these sensations have harmful consequences. AS is thought to play an
      important role as a diathesis for anxiety disorders, particularly panic disorder.
      Recent evidence suggests that AS has a hierarchical structure, consisting of
      multiple lower-order factors, which load on a single higher-order factor. If each
      factor corresponds to a discrete mechanism, then the results suggest that AS
      arises from a hierarchic arrangement of mechanisms. A problem with previous
      studies is that they were based on the 16-item Anxiety Sensitivity Index (ASI),
      which may not contain enough items to reveal the type and number of lower-order
      factors. Accordingly, we developed the 60-item Anxiety Sensitivity Profile, which
      was administered to 349 university students. Factor analyses revealed four lower
      order factors: (1) Fear of respiratory symptoms, (2) fear of cognitive
      dyscontrol, (3) fear of gastrointestinal symptoms, and (4) fear of cardiac
      symptoms. These loaded on a single higher-order factor. The lower-order factors
      shared variance with the higher-order factor, but also contained unique variance.
      Thus, the results suggest that AS is the product of a general factor, with
      independent contributions from four specific factors.

PMID- 9613016
TI  - Interpersonal consequences of the pursuit of safety.
AB  - Socially anxious (N = 41) and non-anxious (N = 41) individuals participated in a
      getting acquainted situation that was based on the reciprocity self-disclosure
      paradigm. Subjects' appraisals of the situation were manipulated to be either
      positive or negative by highlighting the likelihood of positive or negative
      social outcomes. Subjects' social goals and use of safety behaviors were
      assessed, as were others' reaction to the subjects. As predicted, socially
      anxious individuals elicited significantly more negative responses from others in
      the negative appraisal condition, where they employed safety behaviors, than in
      the positive appraisal condition, where they did not. The results supported a
      cognitive model of social anxiety, rather than alternative explanations.

PMID- 9613017
TI  - Hypochondriasis: the role of fear-confirming reasoning.
AB  - We investigated whether hypochondriacal patients are prone to selectively search
      for danger-confirming information when asked to judge the validity of conditional
      rules in the context of general and health threats. Therefore, hypochodtriacal
      patients (n = 27) and a healthy control group (n = 27) were presented with
      modified Wason Selection Tasks (WSTs) pertaining to general and health threats.
      The WSTs contained safety rules (If P then safe) and danger rules (If P then
      danger). Subjects adopted a verificationistic strategy in case of danger rules
      and tended to look for falsifications in case of safety rules. This danger
      confirming reasoning pattern was similar for both types of contexts and not
      particularly pronounced in hypochondriacal persons. These findings argue against
      the idea that such a reasoning pattern directly causes hypochondriasis. Yet, in
      the presence of anxiogenic (hypochondriasis related) convictions such danger
      confirming reasoning pattern logically serves to maintain or even enhance
      hypochondriacal complaints.

PMID- 9613018
TI  - Conducting exposure treatment in multiple contexts can prevent relapse.
AB  - The acquisition of anxiety disorders (e.g., phobias) is often thought to be
      mediated by classical conditioning processes (e.g., Wolpe, 1958, Psychotherapy by
      reciprocal inhibition Wolpe and Rowan, 1989, Behaviour Research and Therapy, 27,
      583-585). Thus, the success of exposure therapy is possibly a consequence of
      extinction, and factors affecting extinction in Pavlovian conditioning are
      potentially relevant to clinicians who administer exposure therapy. The present
      experiments investigated the effects of conducting extinction in multiple
      contexts using rats as subjects in a conditioned suppression paradigm. In
      Experiment 1, subjects received conditioned stimulus (CS) and unconditioned
      stimulus (US) pairings in one context followed by extinction of that CS in one or
      three other contexts. When tested in an associatively neutral context (i.e.,
      different from those of conditioning or extinction), rats that had received
      extinction in three contexts exhibited less responding to the CS than rats that
      had received extinction in one context. In Experiment 2, CS-US training occurred
      in either one or three contexts, followed by extinction of that CS in three other
      contexts. Testing in a neutral context revealed that rats conditioned in multiple
      contexts showed greater responding to the CS than rats trained in a single
      context. The results are discussed in the framework of memory retrieval, and the
      clinical implications are explored.

PMID- 9613019
TI  - Treating adolescent obsessive-compulsive disorder: applications of the cognitive
      theory.
AB  - The recent cognitive theory of obsessions suggests that catastrophic
      misinterpretations of the significance of one's unwanted intrusive thoughts gives
      rise to, and maintains, obsessions (Rachman, Behaviour Research and Therapy,
      1997). It follows from this that provision of benign interpretations of the
      significance of intrusions is likely to challenge and weaken the catastrophic
      appraisals. This article describes the application of this theory to two
      adolescents with obsessive-compulsive disorder (OCD). The adolescents were
      provided with an alternative, benign interpretation of the significance of
      intrusive thoughts and images using a thought suppression paradigm. It is
      concluded that a personal demonstration using the thought suppression paradigm is
      a helpful clinical tool for the cognitive treatment of obsessions in adolescent
      OCD.

PMID- 9613020
TI  - Methodological advances and developments in the assessment of psychopathy.
AB  - The last decade has witnessed a number of significant methodological advances and
      developments in the assessment of psychopathy. The Psychopathy Checklist-Revised
      and the two-factor model of psychopathy have facilitated the assessment of
      psychopathy and clarified the differential correlates of the personality- and
      behavior-based operationalizations of this syndrome. Although preliminary
      evidence suggests that certain features of psychopathy may be underpinned by a
      latent taxon, the categorical versus dimensional status of psychopathy requires
      clarification. Researchers have accorded increasing attention to the assessment
      of psychopathy in non-criminal samples, although the construct of subclinical
      psychopathy remains controversial. Other recent methodological developments
      include: (a) the extension of the Five-Factor Model and other higher-order
      personality taxonomies to psychopathy; (b) development of a Q-sort methodology to
      permit the assessment of psychopathy by observers; (c) standardized assessment of
      psychopaths' interpersonal behaviors; (d) assessment of psychopathy in children;
      and (e) examination of gender, ethnic, and cross-cultural differences in
      psychopathy.

PMID- 9613021
TI  - Intrusive cognitions, coping strategies and emotional responses in depression,
      post-traumatic stress disorder and a non-clinical population.
AB  - Patients with major depression but not PTSD, patients with PTSD with or without
      comorbid depression, and a sample of non-clinical controls, were interviewed
      about their most prominent intrusive cognition, coping strategies and emotional
      responses. Evaluative thoughts were more likely to be reported by the depressed
      sample and the control sample. They were also common in the PTSD group, but other
      types of intrusions were also common, particularly personal memory. All three
      groups reported a wide variety of different types of intrusive cognition, both
      singly and in combination. These included elaborative cognitions, future-oriented
      thoughts or images that represented an elaboration of a specific personal memory.
      Cognitions were more frequent, unacceptable, and intrusive in the PTSD group in
      the month preceding interview, but the two clinical groups did not differ in the
      use of or effectiveness of coping strategies, or in emotional responses.

PMID- 9613022
TI  - Cognitive and behavioral responses to illness information: the role of health
      anxiety.
AB  - The cognitive-behavioral theory of health anxiety predicts atypical responses in
      health anxious individuals when exposed to health related information. Systematic
      research is still needed to support the theory. This investigation examined 192
      participants varying a subclinical levels of health anxiety, who were randomly
      given feedback on an ostensible diagnostic measure, indicating positive, negative
      or ambiguous risk for health complications. Responses to a cold pressor task were
      then measured. The results indicated that regardless of the type of feedback
      patients were given, health anxious individuals displayed the predicted cognitive
      (e.g. negatively interpreted information) and behavioral responses (e.g.
      increased reassurance seeking). Important and perhaps central cognitions to
      health anxiety were identified. Health anxious individuals regarded themselves to
      be at greater risk for disease overall, and attached greater accuracy to health
      related information. Extending the cognitive-behavioural theory, health anxiety
      was found to be associated with decreased usage of positive somatic monitoring of
      symptoms, suggesting health anxiety may be associated with a failure to engage in
      protective strategies. Health anxiety did not result in cognitive or behavioural
      avoidance of illness information. Clinical implications and future directions for
      research are described.

PMID- 9613023
TI  - Anxiety sensitivity and the pathogenesis of anxiety and depression: evidence for
      symptom specificity.
AB  - Expectancy theory posits that anxiety sensitivity (AS) acts as a specific risk
      factor for the development of anxiety pathology (Reiss, 1991). Previous work
      suggests that AS is a risk factor for anxiety but several reports have found that
      AS is also related to depression. The principal aim of the present study was to
      determine whether anxiety sensitivity acts as a specific vulnerability factor in
      the pathogenesis of anxiety and depression in both a large nonclinical sample (N
      = 1401) as well as a patient sample (N = 53). A covariance analytic strategy
      indicated that AS possesses symptom specificity with respect to anxiety but is
      not predictive of depression when accounting for changes in anxiety symptoms.
      Component analyses suggest, however, that one first-order factor (phrenophobia)
      is likely to account for the association between AS and depression because it is
      non-specific (i.e. associated with unique aspects of both anxiety and
      depression). It is concluded that much of the general association noted between
      anxiety sensitivity and depression is likely to be due to covariation among
      symptoms of anxiety and depression.

PMID- 9613024
TI  - Psychosocial predictors of functional change in recently diagnosed rheumatoid
      arthritis patients.
AB  - In order to examine the influence of active and passive pain-coping strategies
      and social support characteristics on the change in functional status in the
      first stage of the disease in rheumatoid arthritis patients, self-report data and
      clinical and laboratory measures were collected from 91 patients (70% female,
      mean age 57 yr) shortly after diagnosis and 1 yr later. Multiple regression
      analyses indicated that, after taking the influence of demographic variables,
      disease activity and pain into account, a decrease in functional status
      (mobility, self-care, grip strength) after 1 yr could be predicted by an
      initially more frequent use of the passive pain-coping strategies of worrying and
      resting. A decrease in mobility could be additionally predicted by an initially
      smaller social network. Results indicate the impact of passive pain-coping
      strategies and social network characteristics for the prognosis of functional
      outcome in the first stage of the disease and suggest the early manifestation of
      avoidance mechanisms, including behavioral, cognitive-emotional and social
      components, in face of a chronic stressor.

PMID- 9613025
TI  - Attentional disruption is enhanced by the threat of pain.
AB  - Using a primary task paradigm this study investigated whether attentional
      disruption to a low-intensity electrocutaneous pain stimulus is enhanced by the
      threat of intense pain. Healthy volunteers (n = 38) performed a tone
      discrimination task in the presence of two types of distractors (a low-intensity
      electrocutaneous stimulus and a control stimulus) which they were instructed to
      ignore. In some trials, tone probes were presented immediately (250 ms) after
      distractor onset, further on (750 ms) during the distractor, and immediately (250
      ms) after distractor offset. In a threat condition half of the participants were
      informed that a high-intensity painful stimulus would occur. As predicted, those
      participants who received the threat instructions, displayed a specific larger
      disruption of task performance immediately after the onset of the low-intensity
      pain stimulus in comparison with the control group.

PMID- 9613026
TI  - The hierarchic structure of fears.
AB  - Contemporary theories of fears (and phobias) suggest two kinds of etiologic
      factors; those common to all fears (factors influencing fear-proneness) and
      factors specific to particular fears (e.g. specific learning experiences). There
      also may be etiologic factors of intermediate specificity; factors common to some
      but not all fears. The present article describes this hierarchic model of fears,
      which proposes that fears (and phobias) arise from a hierarchy of causal factors,
      ranging from specific to general. The model is supported by factor-analytic
      studies of fear inventories and behavioural-genetic studies of twins. However,
      further research is needed to clarify the number of levels, and to identify
      environmental, psychobiological, and genetic factors at each level of the causal
      hierarchy. The hierarchic model of fears represents a call for research. It
      encourages researchers to take a broad view of etiology by considering factors at
      various levels of causal specificity.

PMID- 9613027
TI  - Generalized anxiety disorder: a preliminary test of a conceptual model.
AB  - This study presents a preliminary test of a conceptual model of Generalized
      Anxiety Disorder (GAD) which is theoretically driven and has clear clinical
      implications. The model's main features are intolerance of uncertainty, beliefs
      about worry, poor problem orientation and cognitive avoidance, Subjects were 24
      GAD patients and 20 non clinical control subjects. The results show that all main
      components of the model were highly related to the discriminant function and that
      intolerance of uncertainty was pivotal in distinguishing GAD patients from non
      clinical subjects. Further, the discriminant function derived from these four
      process variables was very effective for classifying GAD patients and non
      clinical subjects into their respective groups. Overall, 82% of subjects were
      correctly classified as 18 of 24 subjects in the GAD group and 18 of 20 subjects
      in the non clinical group were properly identified. The results are discussed in
      terms of the proposed model of GAD and its clinical implications.

PMID- 9613028
TI  - Selective attention to food-related stimuli in hunger: are attentional biases
      specific to emotional and psychopathological states, or are they also found in
      normal drive states?
AB  - Previous work has indicated that anxiety disorders and eating disorders are
      associated with selective processing of stimuli relevant to patients' concerns
      (e.g. Mathews and MacLeod, 1994; Annual Review of Psychology, 45, 25-50; Channon
      et al., 1988; British Journal of Clinical Psychology, 27, 259-260). A dot probe
      task was used to investigate whether attentional biases are also a feature of a
      normal drive state. Specifically, we examined whether hunger is associated with
      biases in selective attention and in pre-attentive processes for food-relevant
      stimuli. Subjects with high levels of hunger showed a greater attentional bias
      for food-related words presented in a suprathreshold exposure condition (words
      shown for 500 msec), in comparison with those with low hunger. There was no
      evidence in the present study of a hunger-related bias in pre-attentive processes
      (i.e. when words were shown for 14 msec and masked). Results suggest that a non
      emotional motivational state, such as hunger, is associated with a bias in
      certain aspects of information processing, such as selective attention, for
      stimuli that are relevant to the motivational state. Findings are discussed in
      relation to recent research into emotion-related cognitive biases.

PMID- 9613029
TI  - Virtual reality treatment of claustrophobia: a case report.
AB  - The efficacy of a treatment for claustrophobia using only Virtual Reality (VR)
      exposure was examined. The subject was a 43-year-old female who suffered from
      clinically significant distress and impairment and sought psychological therapy.
      Eight individual VR graded exposure sessions were conducted. All self-report
      measures were reduced following VR exposure and were maintained at one month
      follow-up. The necessity of a theoretical framework for this new medium for
      exposure therapy is discussed.

PMID- 9613030
TI  - Management strategies for candidates for protease inhibitors and requiring
      treatment for Mycobacterium tuberculosis. TB/HIV Advisory Committee.

PMID- 9613031
TI  - Respiratory virus surveillance. FluWatch Project.

PMID- 9613032
TI  - Mechanisms of drug allergy.

PMID- 9613033
TI  - Phosphatases and kinases in lymphocyte signaling.

PMID- 9613034
TI  - Involvement of the immune system in TSE pathogenesis.

PMID- 9613035
TI  - Exercise immunology: integration and regulation.

PMID- 9613036
TI  - Xenotransplantation: steps towards a clinical reality.
AB  - It was clear that significant research progress has been made in the two years
      since the last congress, although, as the chairman J.P. Soulillou (Nantes)
      concluded, there were no singular advances announced during the week; rather, it
      was a congress for assimilation of information. It was also apparent that there
      is now an attitude of realism in the xenotransplantation community. The
      prevailing mood is one of cautious optimism, to contrast with the unguarded
      optimism of the previous meeting. The future for clinical xenotransplantation now
      appears more secure than it has been previously.

PMID- 9613037
TI  - High-avidity autoantibodies to cytokines.

PMID- 9613038
TI  - The peptide-binding strategy of the MHC class II I-A molecules.

PMID- 9613039
TI  - Modulation of the immunogenicity of antigenic determinants by their flanking
      residues.

PMID- 9613040
TI  - Superantibody activities: new players in innate and adaptive immune responses.

PMID- 9613041
TI  - Qualitative and quantitative aspects of haematopoietic cell development in the
      mammalian embryo.

PMID- 9613042
TI  - Developmental changes in the differentiation capacity of haematopoietic stem
      cells.

PMID- 9613043
TI  - New technology in diagnosis and treatment of diseases of the pleural space.
AB  - Recent developments in video camera technology, new instruments, and advanced
      surgical techniques have increased the importance of video-assisted thoracoscopic
      surgery (VATS). Currently, VATS offers a new approach in the diagnosis and
      treatment of many thoracic conditions previously treated only by standard
      thoracotomy. In our experience, VATS is a safe, reliable, and effective
      alternative to thoracic surgery. With further improvements and refinements in
      video imaging and endoscopic instruments, more procedures will be technically
      feasible. The long-term results of VATS compared to open thoracotomy will require
      extensive follow up and prospective trials to determine its true value.

PMID- 9613044
TI  - Pulmonary function testing: detection of invalid performance.
AB  - We surveyed physician members of the American Thoracic Society and their
      technicians regarding indicators of the validity of PFTs. Surveys were returned
      by 50 physicians and 52 technicians. Both groups felt that consistency of effort
      and the shape/slope of the curve were important indicators, with behavioral
      observations rated slightly lower. Approximately 38% of physicians and 19% of
      technicians felt that they detected 75% or fewer of individuals giving inadequate
      effort during PFTs. Twenty percent of physicians and 29% of technicians were
      using quantitative criteria other than those recommended by the 1979 "Snowbird"
      technical paper to determine acceptability of PFTs. Twenty-eight percent of
      physicians and 31% of technicians spontaneously indicated that patients pursuing
      compensation or disability claims for pulmonary disorders were most likely to
      give suboptimal effort. Empirical research into the impact and detection of
      suboptimal effort on PFTs is encouraged.

PMID- 9613046
TI  - A disturbing trend.

PMID- 9613045
TI  - Which medical school applicants will become generalists or rural-based
      physicians?
AB  - The hypotheses that data, available at the time when a medical school admission
      decision is made, can be used to predict generalist specialty choice and rural
      practice location were tested. Applicant data, available to admissions committee
      members at the University of Louisville in 1986 and 1987 about the classes of
      1990 and 1991 respectively, were correlated with specialty choice and practice
      location in a retrospective cohort study. Data collected from 1994 to 1996 about
      the 1990 and 1991 graduates were used to develop a mathematical model to predict
      specialty choice and practice location using stepwise logistic regression. These
      models were more accurate in predicting which applicants would not select a
      generalist career (negative predictive value = 80.7%) than those who would
      (positive predictive value = 42.7%) and in predicting those who would not
      practice in a rural location (negative predictive value = 91.9%) than those who
      would (positive predictive value = 37.8%). We conclude that applicant data,
      available at the time admission decisions are made, are of limited value for
      identifying those who will eventually become generalist physicians or practice in
      a rural area. However, the data are useful for identifying those who will not.

PMID- 9613048
TI  - [The studies on tuberculosis present research ideas for medicine].
AB  - I started my medical career as medical mycologist following the first case of
      deep-seated candidiasis in Japan. On the other hand I have been seeing many
      patients with tuberculosis as well as respiratory diseases. In my sense the
      seeing of mycobacterial infections may still remain lot of clinical, biological
      or immunological research ideas in future. I did the studies on muramyl dipeptide
      (MDP) which derived from cell wall substance of mycobacteria. MDP seemed to be
      one of the enhancing immunomodulator for host defense mechanism in particular in
      the immunocompromised host.

PMID- 9613049
TI  - [A clinical study on the background of patients with nontuberculous pulmonary
      mycobacteriosis--predisposing factor and environment].
AB  - We studied the background of 78 patients with pulmonary nontuberculous
      mycobacteriosis from 1992 to 1996, and 56 patients (71.8%) were diagnosed as
      primary infection type and 22 patients (28.2%) as secondary infection type. The
      former consisted of 17 males and 39 females (mean age +/- SD; 67.4 +/- 12.9
      years), and the latter consisted of 13 males and 9 females (mean age +/- SD; 74.0
      +/- 7.5 years). Out of all 83 strains, 67 strains (80.7%) were M. avium complex,
      and out of 36 strains identified either M. avium or M. intracellulare, 34 strains
      (94.4%) were M. intracellulare and 2 strains (5.6%) were M. avium. Many patients
      lived in farming areas along the coast, and 35 patients (62.5%) of primary
      infection type and 11 patients (50%) of secondary infection type were or used to
      be farmers. Nine patients (16.1%) of primary infection type and 6 patients
      (27.3%) of secondary infection type had history of gastroduodenal ulcer, while
      only 3 of all 78 patients had sinusitis. There was a married couple who lived in
      a same house and 2 sisters who lived apart who were proved to have primary
      infection type but cross infection was not demonstrated in either case. The
      development of this disease seems to be related to a genetic susceptibility and
      environmental factors.

PMID- 9613050
TI  - [Structure and antigenicity of the glycopeptidolipid antigen of Mycobacterium
      avium-intracellulare complex (MAC) serovar 16].
AB  - The characteristic lipids and specific surface antigens which typify serotypes of
      Mycobacterium avium-intracellulare complex (MAC) serogroup have been examined.
      The characteristic lipids are recognized as glycopeptidolipid (GPL) antigen
      consisted of short-chain acylated oligosaccharides linked to long-chain fatty
      acyl-D-Phe-D-allo Thr-D-Ala-L-alaninol-O-3, 4-di-O-methyl rhamnose 'core'. The
      lack of information on the properties of GPL antigen from serovar 16 and a large
      number of patients infected with MAC serovar 16 have prompted an examination of
      the chemical structures utilizing the analytical techniques of alditol acetates
      with GC or GC/MS, and making use of FAB/MS and 1H-NMR to analyze the intact GPLs.
      The following structure of serovar 16 GPL antigen was proposed with molecular
      weight: 1933, main fatty acyl component: OH-C32:0, and oligosaccharides: 3-amido
      (2'-methyl, 3'-hydroxy, 4'-methoxy pentanoyl) 3, 6-dideoxy hexose-->4-O-methyl-L
      rhamnose-->L-rhamnose-->L-rhamnose-->6-deoxy-L-talose The unique structure may be
      an important factor in physiological and pathological roles. The GPL antigens
      were highly reactive in ELISA against sera from rabbits hyperimmunized with MAC
      strains, indicating its basic antigenicity. The type-specific antigen of serovar
      16 was also specifically reactive against sera from patients infected with MAC
      serovar 16, but invariant core was not. Apparently, the epitope of GPL antigen of
      serovar 16 was specific oligosaccharides, 3-amido (2'-methyl, 3'-hydroxy, 4'
      methoxy pentanoyl) 3, 6-dideoxy hexose. It was found that the ELISA using GPL
      antigens was particularly useful for the serovar diagnosis of human infections
      with MAC.

PMID- 9613051
TI  - [Lymphocyte chemotactic factor in tuberculous pleural effusion].
AB  - To evaluate whether lymphocyte chemotactic factor is involved in the accumulation
      of lymphocytes in tuberculous pleurisy, we measured lymphocyte chemotactic
      activity in tuberculous pleural effusions, and compared with that in malignant
      pleural effusions and transudate. The lymphocyte chemotactic activity was
      measured in vitro with chemotactic chamber. The cells suspended in the culture
      medium was added to the upper well and the effusions, normal human serum (NHS),
      or culture medium were placed below nitrocellulose filter. The lymphocyte
      migration was quantified by counting the number of cells migrating beyond a
      distance of 70 microns from top of the filter in 5 selected fields. The
      chemotactic activity of the effusions was expressed as a percentage of the
      control migration in the culture medium. When we used the freshly isolated
      peripheral blood lymphocytes as responding cells, the chemotactic activity was
      176.0 +/- 41.3% in tuberculous effusions, 115.1 +/- 53.8% in malignant effusions,
      87.1 +/- 16.1% in transudate, and 113.3 +/- 24.2% in NHS, respectively. The
      activity of tuberculous effusions was significantly higher than that of
      transudate and NHS. When we used PHA-activated lymphocytes, the activity was
      284.4 +/- 159.3% in tuberculous effusions, 123.1 +/- 77.6% in malignant
      effusions, 75.8 +/- 10.3% in transudate, and 52.6 +/- 10.1% in NHS, respectively.
      The activity of tuberculous effusions was significantly higher than that of
      malignant effusions, transudate and NHS. The chemotactic activity of tuberculous
      effusions to PHA-activated lymphocytes was significantly higher than that to
      freshly isolated lymphocytes. The activity was specific for T lymphocytes, and
      showed both chemotaxis and chemokinesis by checkerboard analysis. Gel filtration
      performed with Sephacryl S-200 revealed that the chemotactic activities in a
      tuberculous fluid had three peaks located in the regions between blue dextran and
      immunoglobulin G, near to human albumin and cytochrome c marker. The most potent
      activity was found at the region near human albumin. Lymphocyte chemotactic
      factor in tuberculous effusion may stimulate the migration of T lymphocytes,
      especially the activated T lymphocytes to the pleural spaces.

PMID- 9613052
TI  - [A case of pulmonary tuberculosis complicated with intracranial tuberculous
      abscess].
AB  - A 75-year-old male was admitted to our hospital with complaints of fever and
      cough. Chest X-ray showed infiltrative shadows with cavity, and sputum smears
      were positive for acid-fast bacilli. About 2 months after the initiation of anti
      tuberculous chemotherapy, suddenly generalized convulsion occurred. CT of the
      brain showed the solitary mass with the ring enhancement in the left subcortical
      area. About 4 weeks later, brain aspiration drainage was performed and pus was
      aspirated. He was diagnosed as intracranial tuberculous abscess. After the
      drainage, neurological symptoms disappeared completely and there were no
      recurrence of abscess. Attention should be called to the complication of
      intracranial tuberculosis, especially in cases worsened during anti-tuberculous
      chemotherapy.

PMID- 9613053
TI  - [Aortoiliopelvic lymphadenectomy in surgical treatment of rectal cancer].
AB  - The results of aortoiliopelvic lymphadenectomy in macroscopic changes in
      lymphatic nodes being revealed intraoperatively in 73 patients with locally
      spread rectal cancer, are represented. Morphological examination of the removed
      tissues made it possible to reveal metastatic involvement of paraaortal and iliac
      lymphatic nodes in 57.3% of patients. In 36.9% of cases combined radical
      operations were performed. There were no lethal outcomes. Postoperative
      complications were detected in 37.9% of cases, among them atony of the urine
      bladder in 30.1% and inflammatory processes in pelvic cavity--in 8.2%. And in 9
      men with normal sexual potency before the operation it resulted in impotency
      after surgery. 5-year survival made up 27.4% including cases with metastatic
      involvement of lymphatic nodes--19.3%, and without it--35.7%.

PMID- 9613054
TI  - [Duodeno-gastric reflux and its consequences after resection of stomach by
      Billroth II and Roux methods].
AB  - The severity of the duodenogastral reflux (DGR) and its deteriorative effect on
      the mucous membrane of gastric stump with the help of dynamic scintigraphy of the
      liver, fibrogastroscopy, morphological and morphometrical methods in patients,
      who underwent stomach resection by Billroth-2 and Roux methods, were studied. It
      was established, that after resection of the stomach by Billroth-2, extensive DGR
      appeared, vachiny 14.8%. At the same time extensive inflammatory, atrophyc and
      methaplastic changes are developed in the mucous membrane of the gastric stump
      disregeneration and prolipherative processes were progressing. The optimal
      gastroenteroanastomosis, preventing reflux of duodenal contents into gastric
      stump lumen and development of its extensive morphological changes, is considered
      to be Roux type anastomosis with distal (efferent) loop 40 cm of length (DGR made
      up 0.9%).

PMID- 9613056
TI  - [Diagnosis of chronic duodenal obstruction].
AB  - The results of examination of 111 patients with chronic duodenal obstruction
      (CDO) were analyzed. CDO makes up 3.8% in the whole structure of the diseases of
      the organs of gastro-intestinal tract, and in the structure of the diseases of
      pancreato-duodenal area--6.1%. Mechanical form of CDO was revealed in 43.6% of
      patients, functional--in 51.4%; the disease in compensated stage was detected in
      38.7% of patients, in subcompensated stage--in 52.3% and in decompensated stage-
      in 9.0%. Clinical manifestations of the disease are characterized by diversity of
      symptoms, which necessitates the use of the complex of instrumental examinations.
      For establishment of the causes of CDO, besides the routine methods USE and
      computed tomography were used. In simultaneous contrast of the duodenum, the
      aorta and superior mesenteric artery computed tomography in comparison with other
      methods makes it possible to make more precise diagnosis of mechanical CDO caused
      by arteriomesenterial compression.

PMID- 9613055
TI  - [Possibilities of recanalization of cicatricial strictures of esophagus].
AB  - Long-term results of recanalization of the esophagus by orthograde bouginage
      through the guide and by endoprosthesis post-burn strictures were evaluated in
      105 patients. The application of these methods enabled in 81% of patients to
      achieve steadfast restoration of esophageal continuity, sufficient enough for
      adequate feeding. Orthograde bouginage of the esophagus through the guide showed
      to be effective in 45.5% patients with strictures up to 100 mm length and over 6
      mm in diameter, the end of the bouge being not more than 1.5 kg. Endoprosthetic
      procedure provided to achieve restoration of esophageal continuity in 95% of
      patients.

PMID- 9613057
TI  - [Peritoneal dialysis in treatment of diffuse purulent peritonitis].
AB  - Peritoneal dialysis (PD) as a method of sanitation of the abdominal cavity was
      used in treatment of 221 patients (140 males and 81 females aged 17-89 years)
      with extended purulent peritonitis. In all patients toxic (138) of terminal (83)
      stage of purulent peritonitis was diagnosed. PD was carried dut in flow
      fractional regimen with the use of 10-15 l of isotonic physiologic solution with
      the addition of antibiotics and heparin 4 times per day during 4-6 days. Carrying
      out PD in patients with purulent diffuse peritonitis resulted in improvement of
      general condition of the patients, normalization of hemodynamics, diuresis, and
      in lessening the paresis of gastro-intestinal tract as well as decrease of
      intoxication. Thus, in the group of patients in whom PD was not used the
      mortality rate was high--36%, and including PD in the complex of treatment
      contributed to the decrease of lethality to 23%.

PMID- 9613058
TI  - [Sucking effect of diaphragm and its significance in drainage of abdominal cavity
      during hepatic surgery].
AB  - Investigation of the value of the sucking effect of the diaphragm in 44 patients
      was carried out. The first group consisted of 28 patients who have not undergone
      hepatic resection. The second group included patients after hepatic resections of
      various volume in local pathology. The balloon method in modification of this
      clinic was used for measurement of the value of the sucking effect. In patients
      of the first group the value of sucking effect was almost two times more under
      the right cupula of the diaphragm (130.33 + 4.78 mm of water column) in
      comparison with the left infradiaphragmatic space. It is responsible for presence
      of the slot between the right half of the liver and the diaphragm, which
      aggravates the sucking effect. In the second group of patients the value of the
      sucking effect under the right diaphragmatic cupula was practically the same as
      in patients of the first group. After right-sided hemihepatectomy the value of
      the sucking effect under right cupula of the diaphragm has significantly
      diminished. After resection of the right lobe of the liver as well as after left
      sided hemihepatectomy, or without them, the value of sucking effect under left
      cupula of the diaphragm did not significantly differ. The investigations showed
      that vacuum-aspiration with vacuum of not less than 150 mm water column should be
      used for effective drainage of infradiaphragmatic space.

PMID- 9613059
TI  - [Peculiarities of clinical features and surgical treatment policy in old patients
      with acute cholecystitis].
AB  - The results of treatment of 138 patients with acute cholecystitis aged from 75 to
      89 years are analyzed. Calculous cholecystitis was revealed in 126 patients,
      acalculous cholecystitis--in 12 patients. Cholelythiasis was revealed in 63
      (45.6%), stricture of the large duodenal papilla (LDP)--in 13 (9.4%), combination
      of choledocholithiasis and stricture of LDP--in 16 (11.6%). Mechanical jaundice
      was revealed in 54 (39.1%) patients, purulent cholangitis--in 18 (13%). From 138
      patients 113 (81.8%) underwent surgery. Urgent operations were carried out in 35
      (30.9%), early operations--in 54 (47.8%), delayed operation--in 24 (21.2%)
      patients. Cholecystectomy was performed in 99 patients, it was supplemented with
      choledocholithotomy and various types of external drainage of the duct (n = 28),
      choledochoduodenostomy (in 40), transduodenal papillosphincterotomy (n = 6) and
      endoscopic papillosphincterotomy (n = 7). Cholecystostomy was carried out in 14
      patients (including laparoscopic cholecystostomy, n = 5). Repeated operations
      were performed in 29 patients. Postoperative complications appeared in 28 (24.7%)
      patients. 16 patients (14.1%) died after the operation. The causes of death were
      hepatic functional deficiency (6), peritonitis (2), pancreatic necrosis (1),
      acute cardio-vascular failure (4), pulmonary artery thrombo-embolism (2), acute
      cerebro-vascular failure (1).

PMID- 9613060
TI  - [Minor stenosis of carotid arteries: differential approach in diagnosis and
      surgical treatment].
AB  - The results of treatment of 161 patients with atherosclerotic small degree
      stenoses of carotid arteries (up to 50% of diameter) were analyzed. From them 67
      patients underwent operations for chronic cerebro-vascular failure and 11
      patients--for acute cerebro-vascular failure. 31 patients, who had
      contraindications for surgery or refused it, plasmapheresis procedures were
      carried on, 52 patients with asymptomatic carotid arteries' disease underwent
      conservative treatment. On the base of the results of examination and late
      results of treatment it is shown valid to recommend carotid endarterectomy as a
      prophylactic measure in acute cerebrovascular failure in asymptomatic patients
      who have morphologically unstable plaques of carotid arteries. If there are
      general contraindications for carotid endarterectomy, with the aim of prophylaxis
      of cerebrovascular failure the procedures of plasmapheresis for alteration of
      morphologic structure of plaques are advisable.

PMID- 9613061
TI  - [Choice of level and establishment of limb stump in patients with obliterative
      arteries diseases].
AB  - 335 patients with obliterative diseases of arteries of the low extremities were
      examined. Results of motor rehabilitation depend on the severity of post
      amputation defect of the extremity and functional condition of the stump. The
      lower is the level of the amputation the higher is the effectiveness of the
      rehabilitational measures. Ischemia of femoral stump springs up rarely but its
      course is mare severe than ischemia of the stump of the shin, which is confirmed
      by the data of clinical examination, investigation of biochemical parameters of
      the blood and mortality rate. For prophylaxis of ischemia of the stump it is
      suggested simultaneously with the amputation of the extremity to perform
      reconstructive procedures on the arteries, aimed at restoration of blood flow
      through the profound femoral artery. This policy provides the possibility to form
      a long functional stump of the extremity and to improve results of motor
      rehabilitation.

PMID- 9613062
TI  - [Management of infected wounds and trophic ulcers by low frequency ultrasound].
AB  - The article is devoted to the investigation of the use of low frequency
      ultrasound surgical instrument in treatment of trophic ulcers and infected wounds
      in surgical patients. The method of treatment of these wounds and ulcers by
      cavitation influence through an intermediate medium was established, an
      ultrasound surgical apparatus "SUSA-2lf.02", being used, which has been developed
      and manufactured by AOZT "Medilen"--(St Petersburg). On the base of the
      experience in treatment of 76 patients intensification of diffusion of the
      medical preparations into the tissues was shown, among them--into the deep layers
      of the wound channel. The application of ultrasound provides favourable metabolic
      changes (normalization of pH of the medium), ensures deep diffusion of
      medicamentous preparations into the tissues surrounding the ulcers, and enhances
      therapeutic activity of the preparation.

PMID- 9613063
TI  - [Combined therapy of trophic ulcers with protracted healing].
AB  - The results of treatment of 126 patients with trophic ulcers of the low
      extremities were analyzed. Trophic ulcers in 74 patients (58.7%) appeared due to
      postthrombophlebitic disease, in 25 patients (19.8%) due to primary varicose
      veins of lower limbs, in 15 (11.9%) patients due to obliterative diseases of
      peripheral vessels and in 12 (9.5%)--other diseases. The duration of the illness
      made up from 1 to 50 years. In 26 patients (group 1) low-intensity laser
      irradiation (LLI) was used together with combined conservative therapy; in 32
      patients (group 2) hyperbaric oxygenation (HBO), in 21 (3 group)--combined
      application of LLI and HBO was used. The examination of regional
      macrohemodynamics and microcirculation in 39 patients showed decrease of
      rheographic index (RI) in the shin, increase of the arterioles tone and venous
      outflow disturbance. The use of LLI and HBO resulted in undoubtful increase of RI
      and improvement of microcirculatory indexes. As a result of combined application
      of LLI and HBO microflora of the ulcers lowered from 10 and 10 per 1 gr in
      patients of group 1 and 2, respectively, in patients of group 3 there was no
      growth of pathogenic microflora. The investigation of humoral and cellular
      immunity after the application of LLI and HBO demonstrated strong
      immunocorrective action.

PMID- 9613064
TI  - [Prospects and possibilities of prophylactic washing of surgical wounds by
      pulsating spurs of liquid under pressure].
AB  - For bathing of surgical wounds as prophylaxis of wound infection, original
      apparatus which provides running of the liquid into the wound as impulse
      pulsating liquid spurts under pressure, is proposed. Washing of surgical wounds
      by pulsating spurs of liquid diminishes primary dissemination 1000 times and does
      not produce traumatic action on tissues, promotes washing out blood, fibrin and
      devitalized tissues from the wound which contributed to favourable healing.
      Prophylactic bathing of surgical wounds was used in clinic during 384 surgical
      interventions in abdominal cavity, which resulted in decrease of frequency of
      wound complications more than 5 times and reduction of hospitalization period
      after surgery.

PMID- 9613065
TI  - [One-stage elimination of bilateral inguinal and femoral hernias].
AB  - The method of preperitoneal hernioplasty for simultaneous elimination of inguinal
      and femoral hernias was developed, which consists in that semi-oval cross-section
      of the skin is performed 3-4 cm above inguinal ligament. The approach through the
      aponeurosis of superficial oblique (abdominal) muscle is made above the inguinal
      channel, the muscles are retracted by blunt manner, and through the incision in
      transversal fascia they penetrate into preperitoneal space. When doing plastics
      the posterior wall of inguinal channel is strengthened. The tendon of internal
      oblique and transversal muscles are sutured together as well as lateral margin of
      the vagina of rectal muscle with pectineal ligament. Transverse fascia is sutured
      as duplication by the second row of nodular and the interior orifice of inguinal
      channel is reconstructed.

PMID- 9613066
TI  - [Late purulent complication after nephrectomy ("ligature" abscess of
      retroperitoneal space)].

PMID- 9613067
TI  - [Operation of Duhamel with use of suturing apparatus].

PMID- 9613068
TI  - [Ultracaine-new anesthetic drug in cosmetic surgery].

PMID- 9613069
TI  - [Surgical tactics in metastatic lesions of liver].

PMID- 9613070
TI  - [Ileus of stomach].

PMID- 9613071
TI  - [Aleksei Petrovich Krymov (the 125th anniversary)].

PMID- 9613072
TI  - [Human rights and biomedical ethics].

PMID- 9613073
TI  - [Organic hyperinsulinism].

PMID- 9613074
TI  - [Duodenitis: etiology, pathogenesis, classification, manifestations and
      diagnosis].

PMID- 9613075
TI  - [Updated treatment and prevention of erysipelas].

PMID- 9613076
TI  - [Diastolic function of left ventricular myocardium in menopausal
      myocardiodystrophy].

PMID- 9613077
TI  - [Prolactin levels in patients with systemic scleroderma].

PMID- 9613078
TI  - [Time-dependent hemodynamic effects of monosan (Isosorbide-5-mononitrate) in
      anginal patients].
AB  - Chronosensitivity to monosan was studied in acute clinicopharmacological tests at
      7.00, 11.00, 15.00, 19.00 and 23.00 in 20 patients with ischemic heart disease,
      angina pectoris (class II-III). Arterial pressure, heart rate, hemodynamic
      parameters were measured before monosan intake, 1.5, 2, 3 and 21 hours after the
      intake of 20 mg. The findings indicate the existence of chronosensitivity of
      hemodynamics to monosan, circadian rhythm of sensitivity of the heart rate,
      systolic pressure, peripheral resistance. Acrophase of the sensitivity rhythm of
      the heart rate occurred at 13.42, systolic pressure at 21.54, mean arterial
      pressure at 00.41, total and peripheral resistance at 14.13, 15.18, respectively.

PMID- 9613079
TI  - [Peculiarities of treating endocrine ophthalmopathy in patients with toxic goiter
      combined with diabetes mellitus].
AB  - Thyroid pathology is among autoimmune diseases the incidence of which is now on
      the increase. Endocrine ophthalmology (EO) often accompanying thyroid disorders
      may cause deterioration or loss of vision. EO can be corrected by several
      methods. The most pronounced effect is achieved by x-ray therapy on the orbit and
      intermittent glucocorticosteroid (GCS) large-dose therapy. GCS, however, affect
      carbohydrate metabolism. In physiological levels, GCS effects on regulation of
      carbohydrate metabolism are not significant, but high GCS concentrations may
      provoke hyperglycemia and even steroid diabetes.

PMID- 9613080
TI  - [Treatment and prevention of hyper- and dyslipidemia with magnesium-containing
      drugs].

PMID- 9613081
TI  - [Chronopharmacodynamics of betacap (long-acting propranolol) in patients with
      hypertension stage II].
AB  - Chronopharmacodynamics of long-action propranolol hydrochloride-betacap (Natko,
      India) was studied in 48 patients with essential hypertension stage II. Six
      randomized groups of patients were given a single dose of 80 mg a day: at 7, 10
      a.m., 1, 4, 7 and 10 p.m. Before the treatment, 1.5, 2, 3 and 4 hours after
      betacap intake, 10 days after the treatment course noninvasive tests of
      hemodynamics were made. Maximal negative chronotropic and hypotensive effect was
      demonstrated at 10 p.m., 7 and 10 a.m. The hypotensive effect was hemodynamically
      insured either through inhibition of the heart rate alone in the intake at 1 and
      4 p.m. or both inhibition of the heart rate and decreased total peripheral
      vascular resistance in the intake at 7 a.m. and 10 p.m., or negative inotropic
      action of betacap combined with negative chronotropic effect in the intake at 10
      a.m. and 7 p.m. Energy consumption of the myocardium was reduced. A circadian
      rhythm of sensitivity to betacap is shown for total and specific peripheral
      resistance, rational coefficient, diastolic pressure, energy consumption with
      acrophase at early morning hours, left ventricular contractility at night time,
      systolic pressure, double production, stroke index, effective activity of the
      heart at day time.

PMID- 9613082
TI  - [The problem of genetic-biochemical basis of individual sensitivity in
      occupational medicine].
AB  - Human sensitivity to various factors of occupational environment (toxic
      chemicals, aerosols with mostly fibrogenic effects, etc.) depends on individual
      hereditary features determining adaptation or dysadaptation with subsequent
      disease. Studies of propensity and resistance in individuals exposed to
      occupational hazards should cover analysis of genetic basis for polymorphism in
      certain biochemical systems determining relationships between hazards
      detoxication and activation, DNA alteration and repair.

PMID- 9613083
TI  - [Physiological-clinical evaluation of combined impact of local vibrations, noise
      and warming microclimate on miners].
AB  - Chamber experiments covered 3 groups--miners of surface mine levels, those of the
      deep levels and examinees having no adaptation to mine--to evaluate combined
      effects of local vibration, noise and heating microclimate. Human resistance
      against the stated above factors appeared to be a nonlinear system. Induced by
      vibration and heating, divergent changes of sensitivity to vibration and
      dyastolic blood pressure appeared only in the examinees having no adaptation to
      mine, but not in the miners. The studied occupational factors were not
      antagonistic. The results obtained necessitate different regulation of
      microclimate for surface and deep mine levels, in order to consider adaptational
      peculiarities of miners.

PMID- 9613084
TI  - [The functional status of the myocardium in patients with vibration disease from
      the impact of the local vibration].
AB  - ECG, echo-CG and poly-CG examination of 61 workers with vibration disease
      revealed in most subjects hyperkinetic type of blood circulation, reduced
      variability of cardiac rhythm in orthostatic test and increased weight of left
      ventricle myocardium in 60.3% of the subjects. The authors consider the changes
      functional.

PMID- 9613085
TI  - [The immune system status after the impact from local vibrations].
AB  - The article presents results of immunologic studies in 111 vibration disease
      sufferers with variable exposure, age, sex and severity of disease. The examinees
      were proved to have depressed cellular immunity--lower E-RFC count with decreased
      number of active E-RFC and levamisole--correctable modifications of T-cells;
      inhibited humoral immunity--lower levels of IgM, IgG, IgA; contradictory changes
      of neutrophils functions--depressed phagocytosis and metabolic activity with
      pronounced rosette formation; halted immune factors of saliva.

PMID- 9613086
TI  - [The evaluation of indices of noise impact on humans].
AB  - Due to noise, information processing changes, rate and quality of work
      deteriorate. Laboratory experiments prove noise exposure to increase dyastolic
      blood pressure. Multiple factors of occupational environment induce significant
      individual variability of blood pressure, putting a little value to blood
      pressure changes. Functional changes of visual analyzer are expressed by reliable
      increase in eye electrical sensitivity threshold and by lower acuity of vision.
      Changes in oculomotory coordination are expressed by longer performance time and
      higher error rate. The authors discuss possible use of psychophysiologic methods
      to evaluate influence of noise on humans.

PMID- 9613087
TI  - [Occupational medicine: health protection of liquidation specialists].
AB  - Taking long-term clinical and epidemiologic observation of rescue team
      (helicopter pilots) as an example, the authors defined principal concepts
      concerning prophylaxis, social security and rehabilitation of Chernobyl plant
      accident liquidators. Methodology and methods of the liquidators' health care are
      discussed.

PMID- 9613088
TI  - [The decrease of risk of occupational diseases among rail road workers: future
      strategies].
AB  - Diagnosis, registration and prophylaxis of occupational diseases among railway
      workers remain unsatisfactory so far. Thus, creation of the Railway Register of
      Occupational Diseases is essential. The Register includes several blocks related
      to each other and covering enterprises, medical and social institutions. Given
      relatively low primary occupational morbidity in railway transport, the
      Register's software considers incidence of occupational diseases in Russian
      Federation among analogous occupations, matched in working environment classes,
      length of service and occupational hazard. The authors obtained the matched
      incidences of occupational diseases, and can extrapolate the relationships
      revealed to railway workers, forecast high risk of occupational diseases among
      these workers.

PMID- 9613089
TI  - [The investigation of adaptation processes in sheet metal workers].
AB  - The study covered 100 individuals long working in hot metallurgic shops (forging
      and nonferrous metals processing) under unfavorable occupational conditions.
      Heating microclimate appeared to be leading occupational hazard. Adaptation to
      occupational environment was studied in all the examinees and 4 groups were
      defined according to the adaptation level and functional state of cardiovascular
      system. The study also included testing of psychiatric balneologic complex-
      bromide and iodine baths with magnetic laser therapy on Zakharyin-Ged zones.

PMID- 9613090
TI  - Identifying dentistry's ills.

PMID- 9613091
TI  - Protecting your dental license.
AB  - In this second installment in our series about licensing, we explore how actions
      taken by governmental agencies other than criminal courts or professional
      disciplinary agencies, can affect your dental license.

PMID- 9613092
TI  - Occupational health of the dental team.

PMID- 9613093
TI  - Occupational diseases in dentistry. Introduction and epidemiology.
AB  - Health care workers are exposed to a wide range of physical, chemical, biological
      and psychological hazards. However, since blood and airborne pathogens represent
      a tangible risk, infectious diseases are of greater importance to health care
      workers.

PMID- 9613094
TI  - Infectious diseases and the dental office.
AB  - Dentists and other health care workers have long been concerned about a variety
      of infectious agents that may be transmitted within the dental setting. In recent
      years there has also been widespread concern among the general public. Many
      infectious diseases, including HIV, hepatitis, tuberculosis and syphilis, are
      important both because of their potential transmissibility and because the first
      manifestations of the disease may appear in the oral cavity. A knowledge of these
      diseases will allow the practitioner to recognize associated lesions and also to
      take appropriate steps to minimize the risk of transmission in the dental office.

PMID- 9613095
TI  - Risks of occupational exposure to latex gloves.
AB  - The extraordinary increase in latex glove use in dentistry within the past decade
      has created a potential occupational hazard in the form of adverse reactions to
      components found in these gloves. Reactions may range from dry, itchy skin to a
      life-threatening, anaphylactic response. Management of these conditions may be as
      simple as switching glove brands; but in the most severe cases, it may entail the
      need to create a latex-free environment for the safety of the affected health
      care worker. This article reviews the pathophysiology, epidemiology, diagnosis
      and management of these conditions and provides references for more in-depth
      reading on the subject.

PMID- 9613096
TI  - Mercury as a potential hazard for the dental practitioner.
AB  - Mercury has been used for centuries for medical, chemical, metallurgical and
      electrical applications. It is an element of mystery, which in its metallic form
      is an enticing silvery liquid that can be as fascinating as it is dangerous. Its
      use in dental amalgam has a potential for continuous occupational exposure of
      dental practitioners to mercury vapor. It is imperative that the dental
      practitioner understands the hazards associated with the use of mercury, and
      controls exposures to prevent the development of any untoward effects. This
      article provides an overview of the toxicology of the different forms of mercury
      to which human exposure occurs and addresses safety issues associated with
      mercury vapor, the primary form of mercury encountered in the practice of
      dentistry.

PMID- 9613097
TI  - Musculoskeletal disorders in dentists.
AB  - Occupational injuries involving musculoskeletal tissues are often related to
      repetitive movements of upper limbs and prolonged postures such as sitting and
      standing--activities common in dentistry. Surveys of the incidence of
      musculoskeletal disorders among dentists are few, but in Nebraska, 29 percent of
      more than 1,000 dentists reported symptoms of peripheral neuropathy in the upper
      limbs or neck. The Nebraskan dentists reported that crown and bridge work was
      most likely to evoke altered sensations in their upper limbs. Furthermore, since
      47 percent of carpal tunnel syndrome cases in the general population are work
      related and are often associated with repetitive motions, it is reasonable to
      suspect that dentists may be at risk for this musculoskeletal disorder. And,
      since it is estimated that 60 percent to 80 percent of adults will experience low
      back pain at one time or another, resulting in it being the second leading cause
      of absences from work in the general population, dental practitioners are most
      likely to be among those susceptible to this problem. This article focuses on two
      ailments afflicting dentists: carpal tunnel syndrome and low back pain.

PMID- 9613098
TI  - [Functional involvement of diazepam binding inhibitor (DBI) in the establishment
      of drug dependence].
AB  - In this paper, we have reviewed the possibility of the functional involvement of
      an endogeneous neuropeptide for benzodiazepine receptors, diazepam binding
      inhibitor (DBI), in the development of drug dependence and the establishment of
      its withdrawal symptoms. The cerebral levels of DBI protein and its mRNA
      significantly increased in alcohol-dependent mice, and alcohol-withdrawal caused
      further increases of both DBI protein and its mRNA. These increases in the mouse
      cerebral cortex diminished over 14 days after alcohol-withdrawal. In the
      cerebrocortical neurons, similar patterns of DBI protein and its mRNA were
      observed during long-term exposure to alcohol and after its withdrawal.
      Simultaneous exposures of benzodiazepine receptor agonist, antagonist and inverse
      agonist with alcohol abolished the alcohol-induced increase in DBI mRNA
      expression in the neurons. Furthermore, the DBI contents and its mRNA expressions
      were also increased in the cerebral cortex obtained from nicotine-dependent mice
      and the neurons after long-term treatment with nicotine. The nicotine-induced
      increases in DBI content and its mRNA expression in the mouse cerebral cortex and
      the neurons were completely abolished in the presence of an antagonist for
      nicotinic acetylcholine receptor. These results suggest that the changes in the
      levels of cerebral DBI induced by continuous treatments with alcohol and nicotine
      may be involved in the establishment of dependence by alcohol and nicotine, and
      such changes may be regulated by the benzodiazepine and nicotinic acetylcholine
      receptors, respectively.

PMID- 9613099
TI  - [Construction of illegal drug images and mass media in Japan].
AB  - This study attempts to clarify the drug problem of Japan in terms of images of
      illegal drugs (stimulants, marijuana, and volatile solvents) by comparing (1)
      different types of drugs and (2) differences between generations. Another
      objective of this research was to examine influence by the mass media reports
      with regard to drug incidents which influence upon image formation of illegal
      drugs among people. In this study 488 males from the city of Osaka were chosen by
      a random sampling method and a door to door survey was undertaken utilizing a
      self-administered questionnaire with a partial interview method. It was revealed
      that as a whole negative images such as "dangerous" and "terrible" were still
      widely prevailing and positive image such as "fashionable" was much less
      prevailing. Specially, stimulants were regarded more dangerous compared to
      marijuana and volatile solvents. In contrary, marijuana was regarded more
      fashionable compared to stimulants and volatile solvents. Volatile solvents were
      considered more "intimate" compared to other drugs. With regard to generation
      differences, it was the youth who possessed more positive images towards
      marijuana and more intimate feelings about volatile solvents than other
      generations. Findings show that with regard to news about illegal drug incidents,
      respondents' appraisal of the news of mass media primarily make significant
      influence, as compare to mere cognition, on images of illegal drugs. Furthermore,
      it was revealed that there was likely to result in positive images of illegal
      drugs due to lack of adequate information. From the aspects of education, it was
      suggested that dissemination of information at a vast range and maintenance of
      negative images might become a crucial task.

PMID- 9613100
TI  - Effects of buprenorphine and Ro 15-4513 on delayed death and brain beta-endorphin
      levels in rats treated with cocaine or cocaine-ethanol.
AB  - The present study was aimed at elucidating the relationship between brain beta
      endorphin, which was estimated by the immunofluorescence method, and fatal drug
      toxicities due to cocaine and combined cocaine-ethanol administration, including
      the late fatal toxicities clinically noted. beta-endorphin is an endogenous
      opioid peptide, and its secretion has been suggested to be influenced by
      physiological stresses. Furthermore, since protection against these fatal
      toxicities has been previously reported to be provided by buprenorphine (a ligand
      for opioid receptors) and Ro 15-4513 (a ligand for benzodiazepine receptors),
      this study also focused on the relationship between the effects of these two
      ligands and the changes in brain beta-endorphin immunoreactivity. In the fatal
      toxicity study, a toxic dose (75 mg/kg, i.p.) of cocaine combined with and
      without ethanol (3 g/kg, i.p.) was administered to the rats, with and without
      buprenorphine (0.25, 0.5, 1 mg/kg, i.p.) or Ro 15-4513 (5, 10, 15 mg/kg, i.p.).
      All of the deaths that occurred in these animals were divided into two groups:
      early deaths with early toxic symptoms in which the drugs were detected in the
      tissue samples, and late deaths with late toxic symptoms in which no drugs were
      detected in the samples. Without the administration of buprenorphine or Ro 15
      4513, the frequency of late deaths was higher in the cocaine group as compared to
      the cocaine-ethanol group. The total mortality rate was effectively attenuated by
      treatment with 0.25 mg/kg buprenorphine or 10 mg/kg Ro 15-4513. Following
      treatment with 1 mg/kg buprenorphine or 15 mg/kg Ro 15-4513, the frequency of
      late deaths was significantly enhanced in the cocaine group. The brain and liver
      cocaethylene concentrations were also attenuated in those groups in which the
      total mortality rates were attenuated. In the brain beta-endorphin
      immunoreactivity study, the number of beta-endorphin immunoreactive nerve cells
      at the arcuate nucleus was counted at 3 minutes or 24 hours after the drug
      treatment. At 3 minutes after the drug treatment, the number of weakly
      immunoreactive cells with photographic light absorption values greater than 50%
      was enhanced in the groups in which the frequency of late deaths had been
      increased. In the cocaine-ethanol groups treated with buprenorphine or Ro 15
      4513, this enhancement of weakly immunoreactive cells was observed when the total
      mortality rate was increased, regardless of the type of death. At 24 hours after
      the drug treatment (50 mg/kg cocaine), an enhancement of the weakly
      immunoreactive cells only was observed in all of the groups in which the
      occurrence of toxicities had been enhanced, regardless of the type of toxicity.
      Therefore, it can be concluded that the enhancement of total brain beta-endorphin
      immunoreactivity was closely correlated with the increase in the frequency of
      total fatal toxicities, and that the enhancement of weakly immunoreactive cells
      was closely correlated with the increase in the frequency of delayed fatal
      toxicities.

PMID- 9613101
TI  - [Clinical evaluation of hepatic bruit audible in patients with alcoholic
      hepatitis].
AB  - It is well accepted that many patients with alcoholic hepatitis have an audible
      bruit over the liver (hepatic bruit) in western countries. However, this sign has
      not been discussed in Japan. The aim of this study was to assess the significance
      of the hepatic bruit in Japanese patients with alcoholic hepatitis. Hepatic bruit
      was specifically searched for on auscultation by two physician in consecutive
      patients (6 alcoholic hepatitis, 58 other alcoholic liver disease, 128
      nonalcoholic liver disease including 16 hepatocellular carcinoma). Hepatic bruit
      was detected in 5 of 6 (83%) patients with alcoholic hepatitis, and in 1 of 16
      (6%) patients with hepatocellular carcinoma. In any of other liver diseases,
      hepatic bruit was not detected. We conclude that hepatic bruit may be an
      important diagnostic finding in Japanese patient with alcoholic hepatitis as it
      is in western countries.

PMID- 9613102
TI  - [Investigation for polymorphism of ALDH2 exon12 in several Asian areas].
AB  - Mitochondrial aldehyde dehydrogenase (ALDH2) shows genetic polymorphism
      (Glu487Lys substitution) among Mongoloid populations, and the substitution is
      responsible for flushing symptom after alcohol intake. Recently, new ALDH2
      alleles (ALDH2*3 and ALDH2*2Taiwan) in exon12 were reported in North American
      Indians and in Chinese from Taiwan by Novoradskey et al (1995). In the present
      study, we investigated the new allelic variants in exon12 for the five different
      ethnic groups (Mongolian, North Chinese, South Chinese, Myanmar, Japanese) by
      using PCR-SSCP and PCR-direct sequencing. Also, Glu 487 Lys substitution was
      analyzed to obtain additional information on gene geography of ALDH2 alleles in
      Asia reported so far. No new variants were found in the five population groups,
      but ALDH2*2 allele showed different frequencies among these groups. Especially,
      the frequencies of ALDH2*2 in Myanmer (0.02) and Mongolian (0.05) were
      significantly lower than other populations.

PMID- 9613103
TI  - [Mammalian proteins that associate with telomeres].
AB  - Telomeres are the DNA-protein complexes found at the ends of linear chromosomes.
      The structure is believed to be important for chromosome stability and cell
      integrity, and thereby for cell senescence and immortality. Telomeric DNA
      consists of tandemly repeated sequences which are observed from human to yeast.
      For example, human and Saccharomyces telomeres have T2AG3 and TG1-3 repeats,
      respectively. Recently, various protein factors including replication factor C
      (RFC) have been found as telomere repeat sequence binding-proteins.
      Characterization of these proteins and their interactions with telomeres may
      provide a new insight into not only telomere functions but also aging,
      immortality and apoptosis of the cells.

PMID- 9613104
TI  - [Structure and regulation mechanisms of telomerase].
AB  - Telomerase is a specialized type of reverse transcriptase which catalyzes the
      synthesis of telomeric DNA using intrinsic RNA as a template. The enzyme was
      originally found in a ciliate Tetrahymena, and has been extensively investigated
      using ciliates or budding yeast. In mammals, the enzyme is highly active in most
      cancer cells and germ cells, but is inactive in most somatic cells, suggesting
      the activation of telomerase may be important for the continued cell growth or
      progression of cancer cells. Recently, two protein components of the mammalian
      telomerase have been identified using homology to the sequencing data from
      unicellular eukaryotes. Interestingly, telomerase activity was induced by the
      expression of catalytic subunit, hTERT, in telomerase-negative normal fibroblast
      cells, indicating that it plays a key role in the activation of telomerase in
      cancer cells.

PMID- 9613105
TI  - [Telomerase repressor genes].
AB  - Genes involved in the senescence program have been mapped to over ten different
      genetic loci using microcell fusion to introduced human chromosomes and restore
      the senescence program. Multiple pathways of cellular senescence have also been
      demonstrated by chromosome transfer, indicating that the functions of the mapped
      senescence genes are probably difference. Restoration of cellular senescence by
      chromosome 3p or 10p is associated with repression of telomerase function in
      human tumor cell lines, and other chromosomes induced cellular senescence without
      telomerase suppression. This evidence suggests that telomerase suppression and
      thereby telomere shortening is one of several pathways involved in cellular
      senescence.

PMID- 9613106
TI  - [Chromosome rearrangement involving telomeres in cancers].
AB  - Stable maintenance of chromosomes needs the functional telomeres at the
      chromosomal ends. It has been proposed that the loss of telomeric function (LTF)
      plays a major role in the production of abnormal chromosomes, such as the
      telomere association (TA) and the jumping translocation (JT). We analyzed TA and
      JT to evaluate the involvement of LTF in chromosomal instability. A shortened
      telomeres was identified at the fusion point of the JT. We also developed a
      method to examine TA based on PCR and found relationships between telomere
      shortening and products of PCR. Our findings strongly suggest that LTF may cause
      chromosomal instability and contribute to cancer cell evolution.

PMID- 9613107
TI  - [Telomerase downregulation during differentiation of leukemia cells].
AB  - Telomerase activity is often repressed during terminal differentiation of
      immortal cells. We found that activation of mitogen-activated protein kinase
      (MAPK) itself was not sufficient for telomerase downregulation during phorbol
      ester-induced differentiation of leukemia U937 cells whereas a MEK1 inhibitor
      PD98059 inhibited both the differentiation and telomerase downregulation. These
      data indicate that telomerase downregulation is a downstream event of MAPK
      signaling and associated with cell cycle quiescence. Furthermore, drug-induced
      accumulation of the cells at the G0/G1 phase was accompanied by telomerase
      downregulation even without differentiation, whereas that at the S phase by
      enhanced telomerase activity. These data indicate that cancer cells in the midst
      of solid tumor mass might modulate their telomerase activity and exhibit altered
      sensitivity to telomerase inhibitory agents.

PMID- 9613108
TI  - [Application of hammerhead ribozyme targeting telomerase molecule for cancer
      therapy].
AB  - Because telomerase is expressed in most cancer cells, but not in most normal
      somatic cells, telomerase is a promising target molecule of human cancer therapy.
      To reduce telomerase activity in cancer cells, a hammerhead ribozyme is a choice.
      The RNA component of telomerase (hTR) is an essential molecule for telomerase,
      therefore hammerhead ribozyme against it can directly interfere with the
      telomerase activity. The expression level of hEST2, a catalytic subunit of
      telomerase correlates well to telomerase activity. Hammerhead ribozyme against
      hEST2 mRNA, therefore, will reduce telomerase activity by breaking its transcript
      down. Although hammerhead ribozyme can be designed to target any particular three
      base sequences; it is still difficult to predict its efficiency in vivo.
      Application of hammerhead ribozyme targeting hTR is discussed.

PMID- 9613109
TI  - [Application of antisense human telomerase RNA toward cancer therapy].
AB  - We overviewed recent results of anti-tumor effects and inhibition of telomerase
      activity in tumor cells through antisense human telomerase RNA(hTR). By
      introducing antisense hTR expression construct into tumor cells, reduction of
      telomeric DNAs and crisis or cellular senescence occurred in several human cancer
      cell lines. Antisense oligonucleotides to hTR synthesized with peptide nucleic
      acids and phosphorothioate deoxyribonucleic acids(PS) also inhibited telomerase
      activity in vitro. Furthermore, PS antisense hTR had significant effect to
      decrease tumor size and a number of metastatic nodules in a xenograft human
      cancer-nude mouse model. Taken together, the telomerase inhibitors targeting to
      hTR are expected to be novel anti-tumor agents.

PMID- 9613110
TI  - [Telomerase and cancer].
AB  - Telomeres progressively shorten with age in somatic cells in culture and in vivo
      because DNA replication results the loss of sequence at the 5' ends of double
      stranded DNA. Whereas normal somatic cells do not express the enzyme, telomerase,
      which adds repeated telomere sequences to chromosome ends, telomerase activity is
      detected in immortalized and tumor cells in vitro and in tumor tissues. This
      represents an important difference between normal cells and cancer cells,
      indicating that the telomerase activity and/or expression profiles of telomerase
      components are useful markers for cancer biology and detection.

PMID- 9613111
TI  - [Relationship between telomere length and clinical and biological characteristics
      of the cancers with telomerase reactivation].
AB  - Activation of telomerase and stabilization of telomeres are considered to be
      necessary for immortalization of human tumor cells. Telomerase activity and
      telomere lengths were examined in adult and childhood cancer tissues. High
      telomerase activity was detected in over 40% samples. In these cases, the lengths
      of telomeres varied in wide range and the short telomere length significantly
      correlated with high proliferative index. The patients with short telomeres
      demonstrated poorer prognosis than other patients. These findings suggest that
      the short telomeres might be related with the malignant potential in cancers with
      high telomerase activity.

PMID- 9613112
TI  - [Telomerase: a new marker for cancer diagnosis].
AB  - Telomerase, a ribonucleoprotein reverse transcriptase, is expected to be a new
      marker for cancer diagnosis since it has been reported that high expression of
      telomerase activity was detected exclusively in germinal tissues and tumor
      tissues in human body, which is further evaluated by improvement of quantitative
      assay procedure for telomerase activity in tissue extract and by development of
      in situ detection method of telomerase protein component in tissue sections.

PMID- 9613113
TI  - [Methods of measuring telomere length and telomerase activity--practice and
      problems].
AB  - The development of a highly sensitive method for detection of telomerase
      activity, telomeric repeat amplification protocol (TRAP), has provided knowledge
      on telomerase activity in normal and cancer tissues. Subsequent several
      modifications have been achieved, including an introduction of the internal
      standard and hybridization protection technique that leads to simplicity and
      improvement of reproducibility and linearity of this method, and application of
      TRAP to in situ analysis to identify the cells responsible for telomerase
      activity. As for measurement of telomere length, fluorescence in situ
      hybridization technique appeared to give an information of telomere length on an
      individual chromosome in contrast to analysis of terminal restriction fragment, a
      conventional method which can express mean telomere length of all chromosomes.
      Further methodological improvement in this field is ongoing and showing a new
      sight on cell mortality and immortality.

PMID- 9613114
TI  - [Development of in situ TRAP assay detecting telomerase activity in cell].
AB  - Telomerase is a ribonucleoprotein that is detected in more than 85% of primary
      cancer tissues using a telomeric repeat amplification protocol (TRAP) assay.
      Thus, telomerase is considered to be a novel marker for cancer. Telomerase
      activity is not detectable in somatic cells, except for hematopoietic cells and
      cryptic cells in the intestine and hair follicles, thus, detection of telomerase
      is important to delineate clinical implication of telomerase activity. We have
      developed semiquantitative fluorescence-based TRAP assay using fluorescence-end
      labeling primers. Moreover, we also developed an in situ TRAP assay that detects
      telomerase activity at the cellular level. Using these TRAP assays, we are able
      to detect telomerase activity in various kinds of extracts or cytological
      specimens and therefore these applications may have additive information in the
      early detection of cancer and monitoring disease condition.

PMID- 9613115
TI  - [The direct effect of anticancer agents on the telomerase activity in human
      cancer cell lines].
AB  - Telomerase, a ribonucleoprotein that maintains the ends of linear eukaryotic
      chromosomes, is expressed in the majority of malignant cells, while most normal
      somatic cells have no telomerase activity except germline and stem cells.
      Therefore, telomerase activity is considered one of important characteristics of
      tumors. In reviewing the possibility that conventional anticancer agents can
      partly perform their functions through modulation of telomerase. Several data
      including ours suggest that the down-modulation of telomerase activity along with
      inhibition by agents is the secondary event associated with cell death. Moreover,
      cells growth arrested at specific phase of cell cycle by agents still show the
      high level of telomerase activity. Since telomerase activity well correlates to
      the cell viability of treated cells, to study telomerase provides us a new
      implement to examine the sensitivity of cancer cells to agents.

PMID- 9613116
TI  - [Telomerase assay for diagnosis of esophageal cancer].
AB  - Esophageal squamous cell carcinoma is one of the aggressive diseases that has
      poor outcome. Therefore it is appeared that early diagnosis is very important for
      improving its outcome. Iodine staining method is useful for detecting the
      abnormal squamous epithelium and unstaining lesions by iodine contain the early
      esophageal cancers. Recently, telomerase activity that provides an immortal
      capacity for the cells has been measured in many tissues. We measured the
      telomerase activity in the samples of unstaining lesion by iodine using a
      polymerase chain reaction-based assay and described the relation between
      telomerase activity and histopathological findings.

PMID- 9613117
TI  - [Telomerase activity in esophageal squamous cell carcinoma and in normal
      esophageal epithelium adjacent to carcinoma].
AB  - Telomerase activity was analyzed in 52 patients with resected esophageal squamous
      cell carcinoma by telomeric repeat amplification protocol (TRAP) assay.
      Telomerase activity was detected in 41 out of 52 (79%) carcinomas and detected in
      46 out of 52 (89%) normal esophageal epitheliums adjacent to the carcinomas. In
      carcinoma, the telomerase activity was detected more frequently in relatively
      early stages of carcinoma (in 8 of 9 patients with stage 0, in 3 of 3 patients
      with stage I, and in 4 of 4 patients with stage II). However, the telomerase
      activity was detected in only 8 of 12 patients with stage III and in 16 of 21
      patients with stage IV. Thus, the percentage of patients who had tumors without
      telomerase activity increased in more advanced stages. These results indicate
      that telomerase activity may correlate with carcinogenasis of esophageal cancer,
      however, it may not correlate with progression of esophageal squamous cell
      carcinoma.

PMID- 9613118
TI  - [Telomerase activity in esophageal carcinoma and lesions unstained with Lugol's
      solution].
AB  - Telomerase is a specific enzyme required for the replication of telomeres. Its
      activity is detected in almost human cancers. We examined in esophageal carcinoma
      and lesions unstained with Lugol's solution telomerase activity by using
      telomeric repeat amplification protocol (TRAP) assay. Telomerase activity was
      detected in all 22 esophageal carcinomas, regardless of histopathological
      findings. In unstained lesions, telomerase activity was detected in 15 of 22; 10
      squamous cell carcinomas, four dysplasia, one regenerative epithelium, no
      telomerase activity was found in seven; four normal esophageal epithelia, two
      Barrett's esophagi, one regenerative epithelium. These results suggest that
      telomerase activity may be a useful molecular marker for the diagnosis of
      esophageal carcinoma and of the early esophageal carcinoma in area unstained with
      Lugol's solution.

PMID- 9613119
TI  - [Telomere length and telomerase activity in intestinal metaplasia, adenoma and
      well differentiated adenocarcinoma of the stomach].
AB  - We analyzed telomere length and telomerase activity in intestinal metaplasia
      (IM), adenoma, and cancer of the stomach and studied the stages at which the
      cells acquire telomerase activity in carcinogenesis and also the correlation
      between telomerase activity and telomere length. Telomerase activity was detected
      in 15%, 45%, 89% of IM, adenomas, and cancers. Telomere lengths shortened as
      normal mucosa changed into IM and more into adenoma. Gastric cancers showed a
      broad range of telomeric length. The shortest telomere length was found among
      gastric adenomas. These results suggest that telomerase is expressed during early
      phase of gastric carcinogenesis but the activity at that stage is not strong
      enough to fully restore the reduced telomeric DNA.

PMID- 9613120
TI  - [Analysis of expression of human telomerase RNA in gastric precancerous and
      cancerous lesions by using in situ mRNA hybridization].
AB  - We described the localization of human telomerase RNA (hTR) expression in human
      gastric precancerous and cancerous lesions by using in situ mRNA hybridization.
      Diffusely high hTR expression was found in all carcinoma and adenoma tissues.
      Partially high hTR expression was seen in 75% hyperplastic polyps, 47% complete
      type intestinal metaplasia and 21% incomplete-type intestinal metaplasia. All
      chronic gastritis without intestinal metaplasia possessed normal levels of hTR
      expression. The expression of hTR was heterogeneous and infiltrating lymphoid
      cells also expressed high levels of hTR expression. Taken together,
      overexpression of hTR due to stem cell hyperplasia is an early event of
      carcinogenesis of the stomach.

PMID- 9613121
TI  - [Relationship between telomerase activity and clinicopathological findings in
      gastric cancer].
AB  - In recent, telomerase has been drawing the attention, because it plays important
      role in cell immortalization. Since Kim et al exploited TRAP (telomeric repeat
      amplification protocol) assay which detected telomerase activity efficiently,
      telomerase activity of various tissues have been detected. In this study,
      telomerase activity of gastric cancer of resected or biopsy specimen were
      detected. And we have examined relationship between telomerase activity and
      clinicopathological factors. In advanced cancer, telomerase activity is negative
      in 2 cases and positive in 17 cases. In case with lymph node metastasis, negative
      in 3 cases and positive in 14 cases. In differentiated type, negative 1 cases and
      positive 20 cases. In noncancerous gastric mucosa, telomerase activity is
      positive in only 2 cases of 9 cases with intestinal metaplasia. Previous results
      were same in biopsy specimen. In summary, telomerase activity was detected in
      76.7% of gastric cancer and most of advanced cancer or differentiated type. Some
      intestinal metaplasia cases with telomerase activity suggested precancerous
      stage.

PMID- 9613122
TI  - [Telomerase activity during the cell cycle in gastric cancer cell lines].
AB  - Telomerase, a ribonucleoprotein that adds telomeric repeats onto chromosome ends,
      is involved in telomere length maintenance and permits unlimited cell
      proliferation. We examined the possibility that higher telomerase activity is
      associated with the replicative phase of the cell cycle using gastric cancer cell
      lines treated with anticancer drugs. Telomerase activity increased at the time
      point of S-phase accumulation in NUGC-3 cells (5 x 10(5) cells/ml) incubated with
      CDDP (0.5 microgram/ml), paclitaxel (0.01 microM), or VP-16 (1 microM) and in MKN
      28 cells incubated with CDDP. When these cell lines were incubated with 5
      fluorouracil (10 microM) or CPT (0.1 microM), the increase of telomerase activity
      preceded the S-phase accumulation. Our results suggest that telomerase activity
      be regulated by the cell cycle.

PMID- 9613123
TI  - [Diagnostic significance of telomerase activity and telomere length in endoscopic
      sample of colorectal cancer].
AB  - Telomeres are located on both ends of individual chromosomes in eukaryotes. It
      has been reported that telomerase activity and telomere reduction can be detected
      in most human cancers. We examined telomerase activity and telomere length in
      colorectal cancer tissues obtained by colonoscopy. Telomerase activity was
      examined by the TRAP (telomeric repeat amplification protocol) assay and was
      detected in 21 of 26 (81%) primary colorectal carcinoma tissues. Two of 9 (22%)
      colorectal polyp were telomerase positive. Telomere length was analyzed by
      Southern blotting and there was reduction in telomere lengths in 12 of 15 (80%)
      primary colorectal carcinoma and 3 of 6 colorectal polyp, compared to the
      corresponding normal colonic mucosa. Therefore, telomerase activity and telomere
      length may serve as an useful tool for preoperative cancer diagnosis.

PMID- 9613124
TI  - [Detection of telomerase activity in intestinal lavage solution from colorectal
      carcinoma patients].
AB  - In terms of colorectal carcinoma, the fecal occult blood test is widely used for
      mass survey, but has many complicated problems to be overcome. Telomerase
      activity has been reported in a wide range of malignancies. We have examined
      telomerase activity of intestinal lavage solution collected from 16 colorectal
      carcinoma patients and from 10 volunteers (control) by the method of telomeric
      repeat amplification protocol (TRAP) assay. Patients drunk polyethylene glycol
      electrolyte lavage solution (PEG-ELS) before examination. Sample solutions were
      collected by colonoscope at the beginning of colonoscopy. The telomerase activity
      from colorectal carcinoma patients were positive 9/16 (56.3%) including 2 cases
      of early stage. In volunteers, were positive 1/10 (10.0%). This method has,
      therefore, possibility for a new useful method of diagnosis for colorectal
      carcinoma.

PMID- 9613125
TI  - [Telomerase activity in colorectal carcinoma and its relationship to
      clinicopathological findings].
AB  - Telomerase is thought to be responsible for cell immortality. The telomerase
      activity in carcinomas has been remarked since 1995. We examined telomerase
      activity in colorectal carcinoma by TRAP (Telomeric repeat amplification
      protocol) assay, and investigated its relationship to clinicopathological
      findings. We could analyse telomerase activities in 33 cases (66%) of 50
      colorectal carcinomas, whereas the activity was not found in all 13 cases of
      noncancerous colorectal mucosa. There was no relation between the telomerase
      activity and the clinicopathological findings or metastatic status. We confirmed
      telomerase activities in much of colorectal carcinomas in spite of their
      progression. The carcinoma cells might be immortal from their early stage of
      progression by means of telomerase activity.

PMID- 9613126
TI  - [Telomerase activity and genomic instability in colorectal cancers].
AB  - In this study, we investigated the correlation between the telomerase activity
      and the microsatellite instability in colorectal cancers and adenomas. Telomerase
      activity was detected in 75% of cancers and in 33% of adenomas. Microsatellite
      instability was detected in 24% of sporadic cancers, in 54% of multiple cancers,
      and in 22% of adenomas. Telomerase activity and microsatellite instability were
      independent events in colorectal carcinogenesis. The patients with telomerase
      activity and microsatellite instability showed poor prognosis. These results
      indicate that colorectal cancers with both telomerase activity and microsatellite
      instability may have more malignant potential, and adenomas with both them may be
      more intensive precursor of colorectal cancers.

PMID- 9613127
TI  - [Specific activation of telomerase in pancreatic cancer tissue and preoperative
      diagnosis of pancreatic cancer by telomerase in pancreatic juice].
AB  - Telomerase activity was measured in surgically resected tissues in various
      pancreatic diseases. Relative telomerase activity was expressed as the number of
      MIA PaCa-2 cells containing an equivalent activity in 1 microgram protein from
      samples. Telomerase activity in carcinomas was significantly higher than in the
      other nonmalignant pathologic states. Subsequently, telomerase activity was
      measured in pancreatic juice from patients with carcinoma, adenoma, and
      pancreatitis. Telomerase activity in carcinoma samples was significantly higher
      than that in either pancreatitis or adenoma samples as in tissue samples. High
      activity of telomerase in pancreatic juice indicates the existence of pancreatic
      cancer and may serve as a diagnostic tool.

PMID- 9613128
TI  - [Telomerase activity in pancreatic juice for the preoperative diagnosis of
      pancreatic cancer].
AB  - Although many diagnostic challenges have been tried in pancreatic cancer, its
      prognosis still remains poor. One of the reason that it is difficult to diagnose
      using present diagnostic procedure in early stage of pancreatic cancer.
      Therefore, we tried new procedure using telomerase activity from pancreatic
      juice. In this study, telomerase was assayed by use of pancreatic duct cells
      obtained preoperatively from 32 cases with pancreatic duct abnormalities.
      Telomerase activity was undetectable in all 17 subjects with benign pancreatic
      diseases, whereas 13 (87%) of 15 subjects with pancreatic cancer had detectable
      telomerase activity. Interestingly, we also detected telomerase activity in the
      case of carcinoma in situ. If future studies confirm, the detection of telomerase
      activity of pancreatic duct cells may become an useful tool for diagnosis of
      pancreatic cancer, perhaps at early stages.

PMID- 9613129
TI  - [The role of telomerase for pancreatic carcinogenesis in human and hamster].
AB  - Telomerase activity and terminal restriction flagment (TRF) length were
      investigated in human and hamster pancreatic duct adenocarcinomas. In the hamster
      primary and transplantable pancreatic carcinomas and cell lines, telomerase
      activity increased 86 to 215.7 times relative to the levels in normal spleen and
      pancreas, and reduction of TRF length was observed. In 38 human pancreatic ductal
      carcinomas, 32 (84%) exhibited increased telomerase activities with no apparent
      relation to the histological type of tumor, tumor size, regional lymph node
      involvement and distant metastasis. These results suggest that telomerase play an
      important role for pancreatic duct carcinogenesis.

PMID- 9613130
TI  - [Telomere length and telomerase activity in hepatocellular carcinoma].
AB  - Telomerase activity and terminal restriction fragment (TRF) length were examined
      in hepatocellular carcinoma (HCC). Telomerase activity was assayed by telomeric
      repeat amplification protocol (TRAP) connected with an internal telomerase assay
      standard (ITAS). The incidence of strong telomerase activity (highly variable
      level compared with the activity of non-cancerous liver tissue) was 79% in well,
      84% in moderately, and 100% in poorly differentiated HCC, while 0% in non
      cancerous liver tissues. The incidence of TRF length alteration (reduction or
      elongation) was 53% in HCC. The incidence of TRF alteration was significantly
      higher in HCC exceeding 3 cm in diameter, moderately or poorly differentiated in
      histology. Telomerase activity was not associated with TRF length alteration in
      HCC. In conclusion, strong telomerase activity and TRF length alteration
      increased with HCC tumor progressions.

PMID- 9613131
TI  - [Clinical significance of telomerase activity in precancerous lesion of the liver
      (adenomatous hyperplasia)].
AB  - To understand the role of telomere dynamics in hepatocellular carcinogenesis, we
      examined the lengths of terminal restriction fragments (TRFs) in hepatocellular
      carcinoma (HCC) and surrounding tissues with chronic active hepatitis (CAH),
      liver cirrhosis (LC) and atypical adenomatous hyperplasia (AAH). The peak TRFs in
      all HCCs were significantly shorter than those of the surrounding tissues (CAH,
      LC). TRF in AAH was shortened and similar to that of HCC. Telomerase was examined
      in CAH, LC, AH, and HCC, and detected in high levels almost exclusively in HCCs.
      Interestingly, the intensity of telomerase activity in the AH was similar to that
      of HCC. Thus, the progressive shortening of telomere and the activation of
      telomerase may be a useful marker for the early detection of malignant
      progression in liver disease.

PMID- 9613132
TI  - [Usefulness of telomerase activity in the diagnosis of small hepatocellular
      carcinoma].
AB  - The diagnosis of small hepatocellular carcinoma (HCC) is sometimes difficult
      because of the similarity of the histological appearance with adjacent liver
      tissue. Recent advancement of the quantitative telomerase assay can diagnose
      small HCC effectively, and the positive rate surpasses those of alpha-fetoprotein
      and PIVKA-II. The application to a clinical field is, however, limited because
      the small nodules with the possibility of malignant phenotype tend to be treated
      easily with ethanol injection therapy without an additional biopsy for this assay
      only. Further analysis of telomerase related proteins might make it possible to
      visualize the activity in the tissue sections and expand the usefulness of
      telomerase as a diagnostic tool in routine clinical use.

PMID- 9613133
TI  - [Telomerase activity as a novel marker of lung cancer].
AB  - Telomerase activity is found in more than 80% of human malignant neoplasms,
      including lung cancer. Markers with high incidence in malignant samples and very
      low incidence in benign samples are useful in clinical diagnosis of cancer. Thus,
      telomerase activity in clinical materials may become a novel tumor marker of
      existing lung cancer cells. Moreover, since activation of telomerase is
      associated with cellular immortality and its activity level is quite different
      between lung cancer tissues, the activity level may become an indicator of some
      biological features in lung cancer.

PMID- 9613134
TI  - [Significant correlation of telomerase activity in lung adenocarcinomas with cell
      differentiation and chromosome aberration].
AB  - Of a total of 21 surgically resected lung adenocarcinomas (15 men and 6 women
      with an average age of 59.6 yr) well, moderately and poorly differentiated types
      were 6, 7 and 8 cases, respectively. Telomerase activity determined by the TRAP
      assay was classified into four types as follows; negative = Score 0, weakly
      positive = 1, moderately positive = 2, strongly positive = 3. Chromosome
      aberrations were also classified into four groups: Score 0, 1, 2, 3 according to
      the number of marker chromosomes, 0, 1-5 6-15 and over 16 respectively. CT
      Indices (chromosome aberration x telomerase activity) of well, moderately, and
      poorly differentiated types were 1, 4.3, 5.1 respectively. Thus, CT-Indices were
      correlated with cell differentiation in the lung adenocarcinomas (p < 0.01).

PMID- 9613135
TI  - [Prognostic significance of alterations in telomeric repeat length in patients
      with pathological stage I-II non-small cell lung cancer].
AB  - The purpose of this study was to evaluate the correlation between alteration in
      telomere length and prognosis in patients with pathological stage I-II non-small
      cell lung cancer. We measured telomeric repeat length and telomerase activity by
      use of southern blot analysis of terminal restriction fragments and a non
      radioactive ELISA-based assay, respectively. RESULTS: Alterations in TRF lengths
      were present in 17(29.8%) of 57 patients. Patients with altered TRF length had
      significantly shorter survival than did patients without (P = 0.0051). In
      multivariate analysis, only alteration in TRF length independently correlated
      with shortened survival (P = 0.0033).

PMID- 9613136
TI  - [The advantage of an in situ TRAP assay for the detection of telomerase activity
      using bronchial washings obtained from lung cancer patients].
AB  - In most previous reports telomerase activity in lung cancer patients has been
      detected using tissue extracts. We have developed a semiquantitative fluorescence
      based TRAP assay using fluorescence-end-labeling primers. Moreover, we also
      developed an in situ TRAP assay that detects telomerase activity at the cellular
      level. Thus, using these TRAP assays, we can detect telomerase activity in lung
      cancer cells obtained from bronchial washings. A high incidence of lung cancer
      patients with class I-III cytology had detectable telomerase activity, thus, a
      combination of a cell extract based. TRAP assay and an in situ TRAP assay may
      provide additive information to cytology for the diagnosis of lung cancer.

PMID- 9613137
TI  - [Telomerase activity in benign proliferative breast disease and breast cancer].
AB  - The application of telomerase activity is expected to serve as a reliable
      indicator of biological malignancy in breast tumors. We performed a study to
      quantify telomerase activity, the results of which revealed that this activity
      tends to be unexpectedly low in scirrhous carcinoma having low histological
      differentiation. It is therefore felt that additional studies at the tissue level
      using in situ hybridization will be required in the future. Although we think
      that atypical cystic duct is a true pre-cancerous lesion in the sense of having a
      high possibility of progressing into breast cancer, it will be interesting to
      determine whether or not the tissue is composed of cells having telomerase
      activity.

PMID- 9613138
TI  - [Telomere length in breast carcinoma of the young and aged].
AB  - In order to clarify the relationship between the telomeric length of human female
      breast carcinoma cells and patient age, and between telomeric length and the
      histological type of carcinoma, we examined 64 patients (aged 20-89 years) with
      breast carcinoma by histological and southern blot analysis. No difference in the
      telomeric length was recognizable among the three major histological types:
      papillotubular, solid tubular and scirrhous (7.9-8.7 kilobase pairs (kbp)). Mean
      telomere lengths in the groups aged under 35 (8 patients), 36-50 (10 patients),
      51-70 (17 patients), 71-80 (19 patients), and over 81 years (10 patients) were
      11.0, 9.9, 7.0, 7.7 and 7.6 kbp, respectively. There was no significant evidence
      for telomeric shortening in breast carcinoma according to patient age. Two peaks
      of telomeric length were observed in three carcinomas comprising a medullary
      carcinoma and two solid tubular carcinomas showing very prominent lymphocyte
      infiltration histologically.

PMID- 9613139
TI  - [Telomerase activity in association with the pathological differentiation of
      prostate cancer].
AB  - We analyzed the telomerase activity in association with the pathological
      differentiation of prostate cancer. Furthermore, to verify whether the detection
      of telomerase in prostate needle biopsy samples could be valuable for diagnosis,
      we assayed the telomerase activity in needle biopsy samples. Telomerase activity
      was examined by PCR-based telomeric repeat amplification protocol (TRAP) assay.
      Among 31 primary prostate cancer tissues, 28 samples (90%) displayed telomerase
      activity, in which of relative levels were associated with pathological
      differentiation. High activity of telomerase in primary and biopsy samples was
      more frequently detected in poorly differentiated adenocarcinoma. These studies
      suggest that determination of telomerase activity in prostate cancer might be an
      useful examination for detecting prostate cancer and evaluating the biological
      malignant potentials.

PMID- 9613140
TI  - [Quantitative analysis of telomerase activity in exfoliated urothelial cells for
      the diagnosis of bladder carcinoma].
AB  - Voided urine cytology is the most common non-invasive examination for the
      detection and monitoring of bladder cancer. However, the result is not
      satisfactory, especially for low grade tumors. Activity of telomerase can be
      detected in most tissues of bladder carcinoma using the telomeric repeat
      amplification protocol (TRAP) assay. We analyzed the quantitative telomerase
      activity in exfoliated urothelial cells, and evaluated the values for early
      diagnosis of bladder carcinoma. We performed a quantitative analysis using a
      hybridization protection assay (HPA) based on TRAP assay. Telomerase activity was
      significantly higher level in exfoliated urothelial cells from patients with
      bladder cancer than all of healthy cases and patients with benign disease (p <
      0.0001). The cut off value was calculated as mean + 2SD of the telomerase
      activity level of the exfoliated urothelial cells from healthy cases. Using this
      cut off value, telomerase activity was positive in 26 of 41 in exfoliated
      urothelial cells from bladder cancer patients(63.4% sensitivity), and negative in
      63 of 69 in exfoliated urothelial cells from healthy cases and patients with
      benign disease (91.3% specificity). The sensitivity of telomerase activity in
      exfoliated cells was higher than urinary cytology, especially in low grade
      tumors. Our results indicate that quantitative analysis of telomerase activity in
      exfoliated urothelial cells could become minimum invasive and useful method for
      detection of bladder carcinoma.

PMID- 9613141
TI  - [Telomerase activity and determination of cancer in urological neoplasias using
      exfoliated urinary cells: in situ TRAP assay and its application].
AB  - We determined telomerase activity semiquantitatively and in-cell telomerase
      activity in exfoliated urinary cells obtained from urological neoplasias.
      Semiquantitative determination of telomerase activity was performed using a
      fluorescent-based telomeric repeat amplification protocol (TRAP) and telomerase
      activity at the cellular level was determined by an in situ TRAP assay.
      Fluorescent-based TRAP assay detected urinary telomerase activity in about 80%
      patients with urological neoplasia before treatment, whereas urinary cells
      obtained from 30% patients after/during treatment with either chemotherapy or
      operation (class II-V) had detectable telomerase activity. In contrast, the in
      situ TRAP assay detected telomerase-positive cells in 85% patients before
      treatment and 60% patients after/during treatment. Of note is a dissociation of
      the results between fluorescent-based TRAP assay and that of in situ TRAP assay
      in some patients. Some patients without detectable telomerase activity using the
      fluorescent-based TRAP assay showed a low frequency of telomerase-positive cells
      in the urine. A combination of semiquantitative analysis and an in situ TRAP
      assay to detect telomerase-positive cells might be a useful tool in the detection
      and monitoring of patients with urological neoplasias.

PMID- 9613142
TI  - [Telomerase activity in the uterine cervix and the uterine body].
AB  - We have examined telomerase activities in uterine cancer specimens including non
      cancerous normal counterparts by the method of TRAP assay. We detected strong
      telomerase activities in 29 of 30 cervical cancers (96.7%) and all 16 samples of
      endometrial cancer. Normal cervical epithelial tissues obtained from 5
      individuals had very little telomerase activity but were evaluated to be
      diagnostically negative in the activity. In contrast, normal endometrial tissue
      specimens (4 out of 6) had relatively stronger telomerase activities in
      consistent with the result reported previously by others. Most notably, we found
      that dysplastic lesions in the uterine cervix had significant telomerase
      activities. In an attempt to examine the telomerase assay by using cervical
      scraping samples, we have detected the telomerase activity in one case of 12
      (8.3%) normal cervical epithelia, one of 16 (6.3%) cervical dysplasias and 6 of 9
      (66.7%) cervical cancers (stage 0-1b). These present study shows that the
      telomerase assay is useful for the diagnosis of cervical cancers. However, it is
      hampered to evaluate whether or not telomerase activity in endometrial cancer
      specimens is attributable to cancer cells because of the presence of relatively
      strong telomerase activity in normal endometrium. In addition, telomerase
      activities was detectable in scraping samples from uterine cervix which were
      clinically diagnosed as CIS but not dysplasia and normal.

PMID- 9613143
TI  - [Telomerase activity and telomere length as diagnostic tumor marker for ovarian
      tumors].
AB  - Telomerase activity was detected in germ cells, stem cells and cancer cells. In
      tumors of the ovary, an organ that contains germ cells, the authors examined
      availability to detect telomerase activity. Telomerase activity of malignant
      tumors was extremely high compared with that of normal ovaries and benign tumors.
      Strength and frequency of telomerase activity in malignant tumors was significant
      different from that in benign tumors. Telomere length tended to be smaller for
      malignant tumors of advanced stage, but no significant relationship between
      telomere length and telomerase activity and tumor stage could be recognized.
      Telomerase activity may be a useful marker for the diagnosis of ovarian tumors.

PMID- 9613144
TI  - [Analysis for telomerase activity in various hematologic disorders].
AB  - The telomerase activity of various hematologic disorders, including malignant and
      non-malignant ones is discussed in this paper. In total of 137 cases, each
      positivity of telomerase activity was MDS = 17/51, overt leukemia from MDS =
      6/15, AML = 17/21, ALL = 4/6, CML-CP (chronic phase) = 0/10, CML-BC (blastic
      crisis) = 4/4, MPD (myeloproliferative disease)-BC = 3/3, CLL = 1/10, MM
      (multiple myeloma) = 0/6, aplastic anemia = 3/5, essential thrombocytosis = 0/3,
      and polycythemia vera = 1/3. The MPD-BC showed very high level of telomerase
      activity as well as CML-BC cases. From the analysis for 18 cases of AML and/or
      malignant lymphoma patients, significant results showed that the expression of
      cyclin D/E was not related to telomerase activity in these hematologic disease,
      as was not the case with breast cancer which was reported formerly.

PMID- 9613145
TI  - [Telomere and telomerase in the differentiation of leukemic cell lines].
AB  - By using three hematopoietic cell lineages including myelomonocytic,
      erythroblastic and megakaryocytic differentiation, downregulation of telomerase
      activity was found to be a general response to the induction of differentiation.
      The decrease in telomerase activity occurred as early as 24h when HL-60 and K562
      cells were cultured in the presence of VD3, ATRA and hemin and completely
      disappeared after 3 days. On the other hand MEG-01 cells showed dramatic
      inhibition of telomerase activity after 6 days of culture with TPA. Analysis of
      telomeric DNA in HL-60 cells and K562 cells demonstrated no remarkable loss of
      telomeric DNA with cellular differentiation while loosing telomerase activity.
      The repression of telomerase is one of many molecular events during the complex
      process of cellular differentiation, and testing of additional cell lines that
      are capable of differentiation will be helpful for understanding the mechanisms
      of telomerase control.

PMID- 9613146
TI  - [Telomere, telomerase and cytogenetic changes in myelodysplastic syndromes].
AB  - Myelodysplastic syndrome (MDS) is a heterogenous but clonal disorder
      characterized by cytopenia and dysplastic features. Telomere length in MDS vary
      but some of them show shortened telomeres. Telomerase activity in MDS also vary
      but about 60% of them show slightly elevated telomerase activity. According to
      the disease progression of MDS, MDS patients categorize into 3 groups, i.e., (1)
      normal telomere length before and after disease progression, (2) short telomere
      length before and after progression, and (3) shortened telomere with disease
      progression. Telomerase change with disease progression is not obscure,
      indicating impairment of telomere dynamics in MDS. These observations may
      indicate that some MDS show telomerase upregulation possible due to telomere
      shortening, while the another pathway without telomerase upregulation associated
      with complex chromosome changes may link to the pathogenesis of MDS.

PMID- 9613147
TI  - [Development of a dural substitute for preventing prion diseases induced by
      grafting of freeze-dried human dura mater].
AB  - To provide a substitute for the dura mater a new bioabsorbable composite sheet
      was developed. This composite was composed of two L-lactic acid-epsilon
      caprolactone (50:50) copolymer films and a poly (glycolic acid) nonwoven fabric.
      They displayed good mechanical properties and were completely absorbed 24 weeks
      after implantation in the back of rats. Histological evaluation of the composite
      sheet was undertaken by implanting it in 31 rabbits with dural defects and
      examining the sites of implantation 2 weeks to 26 months later. Any infection,
      cerebrospinal fluid leakage, evidence of convulsive disorders, significant
      adhesion to underlying cortex, and calcification was not noticed in any cases. In
      addition, the regenerated duralike tissue had a high pressure-resistant strength
      2 weeks after implantation.

PMID- 9613149
TI  - [Acute necrotizing encephalopathy of childhood: recent advances and future
      prospects].
AB  - Acute necrotizing encephalopathy of childhood (ANE) is a clinicopathological
      entity recently separated from acute encephalopathy of unknown etiologies. The
      hallmark of ANE is multiple, bilateral symmetric brain lesions showing edema and
      necrosis which occur in the bilateral thalami and other specific regions. Since
      its establishment in 1993-1995, data have further accumulated and have provided
      additional insight into its pathogenesis. This review summarizes recent
      achievements on ANE, with reference to issues to be clarified by future studies.

PMID- 9613150
TI  - [Comprehensive approach to cerebral palsy: changes of concept in Japan].
AB  - Cerebral palsy is associated not merely with impairments of posture and
      locomotion, but also with various other problems. Medical illnesses should be
      treated by an adequate system. Emotional disturbances require a psychological
      support. Communication disorders may be overcome with proper modern equipments
      Perceptional deficits and sensory impairments should also be addressed. Care
      systems for physically handicapped children in Japan were established by the
      concept of ryoiku, a term in Japanese created about fifty years ago by K. Takagi,
      Professor of the Department of Orthopedics, University of Tokyo. This term can
      hardly be translated into English, bot in my view stands for a comprehensive
      approach comprising orthopedic treatments, educational programs and vocational
      trainings. Based on this concept, Dr. Takagi founded an institution for the
      physically handicapped in 1942; followed by establishment of similar institutions
      in all areas of Japan after World War II. Despite its historical role, ryoiku
      does not meet any more the current standard of care for cerebral palsy. We need
      now a new comprehensive term and management systems. A novel medical subdivision
      "medicine for developmental handicaps" may also be necessory. In this paper I
      made an overview of current problems of children and adults with cerebral palsy.
      I proposed a new concept of ryoiku and emphasized the need for the new medicine
      to treat developmental handicaps.

PMID- 9613151
TI  - [The relationship of a neonatal care center, a pediatric neurology division and a
      rehabilitation center for disabled children].
AB  - We investigated the relationship of the infants admitted to the neonatal
      intensive care unit (NICU) of Anjo Kosei Hospital, the outpatients of the
      pediatric neurology division of the same hospital and the patients in Daini
      Aoitori Gakuen, Aichi prefectural hospital and Rehabilitation Center for Disabled
      Children. Eighty-six infants (2.9%) disclosed perinatal brain injury, and seventy
      infants (2.3%) had cerebral palsy in a total of 2,985 patients who were admitted
      to the NICU in Anjo Kosei Hospital. Forty seven percent of the outpatients of
      pediatric neurology division had been admitted to NICU. Eighty-four percent of
      the in fants with cerebral palsy had been referred to the Rehabilitation Center
      for Disabled Children. MRI disclosed perinatal brain injury in 72% of patients
      with cerebral palsy. We stress the importance of an information network among
      NICUs, pediatric neurology divisions and rehabilitation centers for disabled
      children.

PMID- 9613152
TI  - [Improvement of QOL by advance in the management of respiratory disorders,
      dysphagia and upper gastrointestinal disorders in children with severe cerebral
      palsy].
AB  - In children with severe cerebral palsy, the daily use of naso-pharyngeal airway,
      daily chest physiotherapy and adequate posture control markedly improve
      respiratory disorders and their consequent complications. Non-invasive
      ventiratory support methods such as nasal IPPV and nasal CPAP can be also
      effective. Enteral feeding through a naso-jejunal catheter can successfully
      manage feeding difficulty due to gastroesophageal reflux when surgical treatment
      is difficult. Exact assessment of aspiration by adequately performed video
      fluoroscopic swallowing examination leads to national management of dysphagia.
      Tube feeding by intermittent oro-gastric catheterization combined with oral
      feeding is useful way in many dysphagic children. Surgical treatment for
      prevention of aspiration markedly improves the general condition. These
      treatments and managements have markedly improved the QOL, of children with
      severe cerebral palsy in many aspects. Cooperation of pediatricians, parents,
      school teachers and other community staffs is necessary for appropriate daily
      management of medical problems of these children.

PMID- 9613153
TI  - [Higher cortical dysfunctions in preterm diplegia: how to evaluate and treat for
      their pedagogical difficulties].
AB  - Preterm diplegic children (SD) frequently suffer pedagogical difficulties. They
      showed visual perceptual impairments and also constructional dyspraxia,
      neuropsychologically. Multiple regression analysis proved that the constructional
      dyspraxia was independent from the impairments of visual acuity, stereoacuity,
      depth perception and visual perception. EEG coherence analysis in SD patients
      disclosed lower interhemispheric coherence at alpha band frequency in occipital
      derivations. The lower coherence value may correspond to thinning of posterior
      body and splenium of corpus callosum in SD patients. A adequate ophthalmological
      treatments, books with enough space between the lines and three dimensional
      models to facilitate the image of stereography are recommended.

PMID- 9613154
TI  - [Development of communication method].
AB  - During the last decade, the idea of self decision have become a very important
      concept for the independent life of children with cerebral palsy. In association
      with this, AAC (augmentative and alternative communication) researches became
      more active to support their communication. Especially, high-tech communication
      aids have enabled speechless cerebral palsied children to speak. However, in
      Japan, there are negative attitudes toward the use of aids in the parents,
      therapists, physicians, and teachers. Consequently, aids are not popular among
      young Japanese children at present. In contrast, there are in US some reports
      showing positive effects of aids. It does not only compensate their disabled
      functions, but also make a chance to communicate with other people. In this
      paper, how communication aids affect habilitation of children with cerebral palsy
      was discussed.

PMID- 9613155
TI  - [Technical aids for children with cerebral palsy].
AB  - A variety of Technical Aids have been developed and adapted for children with
      cerebral palsy. The most important objects of Technical Aids are positioning,
      locomotion and communication. Essencially, Technical Aids are based on assistive
      technologies, and must be applied to the activities of daily living and to
      habilitation for children with cerebral palsy by themselves, their family and the
      professional staff in institutions. It is necessary not only to develop new
      Technical Aids, but also to extend each adaptive measures and applied
      technologies for all local areas.

PMID- 9613156
TI  - [Functional deterioration in adults with cerebral palsy].
AB  - We studied functional deterioration in adults with cerebral palsy working at
      community workshops throughout Japan by interviews and direct examinations. The
      incidence of functional deterioration was 36%, being higher among those with
      involuntary movements of the head and neck, abnormal movement patterns when
      moving and those with reported in poor work environment. In more than one-half
      case, deterioration was associated with inadequate in noise control, lighting,
      air circulation from the cooling and heating systems, height of the chairs and
      desks, and height of VDT screens. Though the factors intrinsic to cerebral palsy
      were often responsible for the functional deterioration, environmental factors
      were also significant. Studies on the work environment as well as medical
      evaluations are needed.

PMID- 9613157
TI  - [The role of neuropaediatrician in the comprehensive management of children with
      cerebral palsy].
AB  - The child with cerebral palsy becomes the adult with cerebral palsy. In Japan
      early detections and treatments of CP have enthusiastically brought into practice
      over the last twenty years. But cerebral palsy could not be cured.
      Children/adults with CP should be provided comprehensive treatments and cares so
      that they can perform their daily activities and fulfil their social roles
      expected during their lifetime. There are two concepts needed to provide
      comprehensive management of CP. The first is a medical model that assesses CP in
      the following manner: etiology-pathology-manifestation. The other is a disability
      model based on three seperate categories suggested by WHO: impairment-disability
      handicap. Keeping these in mind, total effective approaches to children/adults
      with CP were discussed. Neuropaediatricians are asked to play important roles
      which contain epidemiologic activities, early detections, and medical treatments.
      They should refer clients and their families to related professionals if
      necessary and have also knowledges of assisstive equipments to enrich their
      lives.

PMID- 9613158
TI  - [Clinical studies on 35 patients with infection-related acute encephalopathy].
AB  - The findings on magnetic resonance imaging (MRI) or computed tomographic scan in
      35 children with acute encephalopathy (AE) induced by infections were categorized
      into five groups: (1) normal findings (11 cases), (2) normal findings in the
      acute phase followed by mild brain atrophy (1 case), (3) severe brain edema which
      developed within 48 hours after the onset of AE (7 cases), (4) diffuse cortical
      necrosis which appeared around 4 days after the onset of AE (9 cases), and (5)
      symmetric thalamic lesions (7 cases). Their outcomes were as follows: three cases
      developed epilepsy in (1) and (2); six died and one had a sequel of severe brain
      damage (SBD) in (3); all cases survived but had SBD in (4), and four died, one
      had SBD, and 2 recovered in (5). Serum AST were elevated in 7.7 and 6 cases in
      (3), (4) and (5), respectively. In all of them, there were more than one case
      having liver histologies consistent with Reye syndrome.

PMID- 9613159
TI  - [Home mechanical ventilation with nasal intermittent positive pressure
      ventilation for a boy with congenital central hypoventilation syndrome].
AB  - We report a 4-year-old boy with congenital central hypoventilation syndrome
      (CCHS) successfully treated with home mechanical ventilation with nasal
      intermittent positive pressure ventilation (NIPPV) during sleep hours. He had had
      frequent severe apneic attacks from the neonatal period. At 8 months, he was
      treated with positive pressure ventilation following a tracheostomy. At 4 year
      and 2 months, NIPPV was attempted because of recurrent respiratory tract
      infections and cor pulmonale. The tracheostomy was successfully abandoned 6
      months later. Adequate ventilation has been maintained for more than 3 years
      without troubles. NIPPV is an effective and non-invasive treatment of CCHS that
      it significantly improves the quality of life during daytime.

PMID- 9613160
TI  - [Dramatic improvement with immunoabsorption therapy in a 7-year-old girl with
      severe Guillain-Barre syndrome after unsuccessful gammaglobulin therapy].
AB  - We report a 7-year-old girl with severe Guillain-Barre syndrome (GBS) who showed
      dramatic improvement after immunoabsorption therapy. She had progressive muscle
      weakness with resultant respiratory failure. On the 7th day of the illness, she
      was nearly quadriplegic and dependent on mechanical ventilation. In addition, she
      had autonomic manifestations, areflexia, abolished or delayed peripheral nerve
      conduction, and increased CSF protein. Administration of a high dose of
      gammaglobulin failed to improve the symptoms. Immunoabsorption therapy using a
      tryptophan column was performed 9 times during 17 days. After 5 times of
      immunoabsorption therapy, the muscle weakness improved dramatically; she was
      extubated 16 days after the institution of the therapy and walked without
      assistance on the 41st day. She regained normal muscle power without any
      sequelae. The immunoabsorption therapy caused hemolysis and decrease of serum
      fibrinogen, but no serious complications. The clinical course of this patient
      suggests the efficacy of immunoabsorption therapy in GBS.

PMID- 9613161
TI  - [Prospects of international cooperation in the field of pediatric neurology].

PMID- 9613162
TI  - [Tuberculosis at the threshold of the 21st century].
AB  - The author summarizes the most important results of the present history of
      tuberculosis obtained both in Hungary and abroad. He deals with the state of the
      art of the tuberculosis epidemics all over the world and in Hungary, presenting
      also the potential genetic risks. He also discusses the risk groups with special
      regard to the extremely large regional differences, searching for the underlying
      causes, as well as to that of the relationships between the epidemic and the
      social factors. He reviews the up-to-date methods of the diagnostics of
      Mycobacterium tuberculosis. He evaluates the significance of mass screening in
      the early diagnosis of tuberculosis and lung cancer in Hungary. He gives an
      overview of the current strategy of treatment, of the principals of directly
      observed therapy short course (DOTS) and the international results obtained. In
      the Hungarian surveillance programme, these principles are adapted under domestic
      conditions. Based on the data from Hungary and abroad, he presents the risk of
      development of multidrug-resistant strains and the mechanism of their
      development, presuming that genetic methods will also play a role in the future
      management of tuberculosis.

PMID- 9613164
TI  - [Nutritional value of polyunsaturated fatty acids].
AB  - Recently, the scientific interest trends toward the role of polyunsaturated fatty
      acids (PUFAs) in human nutrition because of their multifunctional properties.
      This study shortly summarizes our knowledge on the metabolism and physiological
      importance of PUFAs belonging to the n-6 and n-3 families. The main PUFAs of
      nutritional interest are linoleic (C18:2n-6), alpha-linolenic (C18:3n-3) acids
      and their derivates, namely arachidonic (C20:4n-6), eicosapentaenoic (C20:5n-3)
      and docosahexaenoic (C22:6n-3) acids, respectively. These fatty acids are
      incorporated into membrane phospholipids of cells where they support cell
      membrane integrity and function. Furthermore, arachidonic and eicosapentaenoic
      acids are precursors for eicosanoids. Eicosanoids, such as thromboxanes,
      prostacyclins and leucotrienes are important in the regulation of several
      physiological processes. PUFAs, especially docosahexaenoic acid are essential
      nutrients in early human development, namely for neural tissues, such as the
      brain and the retina. According to our study the n-3 PUFAs supply of pregnant
      women and neonates were inadequate. In conformity with our calculation the same
      is true for the whole Hungarian population. On the basis of these findings we
      call attention to the necessity of changing the structure of fat consumption and
      we commit to a recommendation for it.

PMID- 9613163
TI  - [Effect of chronic amiodarone therapy on left ventricular function in dilated
      cardiomyopathy studied by the new Doppler-index].
AB  - Several noninvasive techniques have been used for the assessment of systolic and
      diastolic function. In most forms of cardiac disease however systolic and
      diastolic dysfunction coexist, hence a combined measure of left ventricular
      performance may be more reflective than their assessment alone. A recently
      recommended new Doppler index is supposed to be useful for this purpose. This
      index is the ratio of the sum of both isovolumic times and the ejection time. The
      objective of this study was to assess the features of the new index and then to
      prospectively evaluate the effect of chronic amiodarone treatment on left
      ventricular function using the new index and standard methods in dilated
      cardiomyopathy. RESULTS: Normal values of the new index are within a narrow
      range, it separates the normal and the dilated cardiomyopathy patients without
      overlap, it is not heart rate dependent in either group and it is not affected by
      either mitral regurgitation or left bundle brunch block. The index is inversely
      related to the relative diastolic filling time in both groups. In severe dilated
      cardiomyopathy after one year amiodarone treatment there was a significant
      decrease of heart rate, the new Doppler index and a significant increase of
      ejection fraction, ejection time and relative diastolic filling time. These
      changes were significant already at 1 month except the new index. These results
      suggest that the beneficial effect of amiodarone is due to the increase of
      diastolic filling time rather than to a positive inotropic effect. CONCLUSIONS:
      1. The new Doppler index is simple and can be easily utilized in the
      differentiation of normal and abnormal left ventricular function: 2 chronic
      amiodarone treatment may be indicated even in the absence of arrhythmia to
      improve left ventricular function in severe heart failure.

PMID- 9613165
TI  - [Incidence of factor V G1681A (Leiden) mutation in samplings from the Hungarian
      population].
AB  - Thromboembolic disorders affect 0.1% of the adult population. Two main groups of
      the underlying predisposition factors can be identified: environmental factors
      (e.g. dietary habits, physical activity, surgical interventions, pregnancy etc.)
      and several genetic predispositions (e.g. inherited anticoagulant defects). After
      the discovery of the genetic mutation of factor V, called Leiden mutation, it
      turned out, that this mutation is responsible for the development of resistance
      to activated protein C in majority of the cases. The importance of the Leiden
      mutation is further emphasised by population based investigations, which makes it
      the most frequent thrombosis risk factor known today. In our study we have
      identified 43 heterozygotes and 3 homozygotes with Leiden mutation in total of
      665 samples. The 6.47% heterozigocy is in the range of earlier reports from
      Europe. The homozygote/heterozygote distribution deviated from the value
      predicted by the Hardy-Weinberg law.

PMID- 9613166
TI  - [Simultaneous occurrence of hereditary angioneurotic edema and Crohn disease].
AB  - Hereditary C1 esterase inhibitor deficiency is often associated with
      immunpathologic disorders. The authors present a case of the rare coincidence of
      hereditary angioedema (HAE) and Crohn's disease. The history of the patient is
      analysed along with the familial occurrence of the disease. Characteristic
      abdominal manifestations of C1 esterase inhibitor deficiency are compared to the
      clinical signs of Crohn's disease. Differential diagnostic pitfalls are described
      along with efficatious therapeutic options.

PMID- 9613167
TI  - [Physician-patient relations].

PMID- 9613169
TI  - [Paracetamol].

PMID- 9613168
TI  - [Unusual complication of Crohn disease: perforation of the abdominal cavity].

PMID- 9613170
TI  - Enterovirus infections.

PMID- 9613171
TI  - Adolescent school failure: failure to thrive in adolescence.
AB  - The role of the primary clinician in dealing with school failure can be critical
      by linking the epidemiological with the clinical and encompassing the
      pediatric/adolescent life span. It includes components of social and public
      health advocacy, preventive medicine, evaluation, education, treatment, and
      referral. The most effective interventions are early and multifaceted. The
      primary care role includes: community advocacy; counseling about prenatal drug
      and alcohol abuse; early detection and treatment for attentional disorders,
      underachievement, and learning disabilities; interviews addressing multiple risk
      factors, grades, school attitudes, behavior, and friends; anticipatory guidance;
      education about individual learning style and good "learning hygiene"; early
      referral and intervention for preadolescent conduct problems and parent-child
      conflict; early referrals for family distress; and prevention of substance abuse
      and adolescent pregnancy.

PMID- 9613172
TI  - Hematuria.

PMID- 9613173
TI  - [Formation and sociomedical characteristics of antituberculous dispensary
      contingents registry group IA patients].
AB  - There are 77.1% of new cases in antituberculous dispensary registry group IA. The
      proportion of patients diagnosed at hospitals of different disciplines has been
      higher that of patients identified at preventive fluorography. In 18.3% of cases,
      group IA has been replenished by patients with exacerbation and recrudescence;
      4.6% has come from imprisonments, 17.8% of antituberculous dispensary registry
      group IA patients are socially disadaptive. The most severe destructive forms of
      tuberculosis with bacterial isolates detected at bacterioscopy are common mainly
      in patients whose disease has been diagnosed due to pulmonary complains in
      polyclinics and hospitals. Various concomitant diseases are present in 82.3%,
      10.3% of patients are followed up in group IA for more than 3 years.

PMID- 9613174
TI  - [Inpatient treatment of pulmonary tuberculosis: present day status and
      prospects].
AB  - Analyzing the duration and efficiency of treatment of 95 inpatients with first
      detected pulmonary tuberculosis indicated that the mean hospital stay of patients
      without and with decay was 205 and 291 days, respectively. Medical and social
      aspects should be considered while defining indications and hospital stay periods
      in patients with tuberculosis. Long-term hospitalization of the patients is
      justifiable only in complicated tuberculosis and special circumstances which
      require direct continuous follow-up.

PMID- 9613175
TI  - [Specific features of diagnosis and treatment of patients with pulmonary
      sarcoidosis and tuberculosis].
AB  - In the past 30 years, the authors examined and treated 6473 patients with
      pulmonary sarcoidosis, of them 105 (1.6%) had contacted with the individuals
      isolating Mycobacterium tuberculosis and 45 (0.7%) had a history of various forms
      of pulmonary tuberculosis; however, the patients with pulmonary sarcoidosis had
      neither exacerbations nor relapses. Of the 6473 patients, 41 (0.63%) was
      diagnosed as having active pulmonary tuberculosis, including 20 with focal
      pulmonary tuberculosis, 13 with disseminated pulmonary tuberculosis, 4 pulmonary
      tuberculosis with infiltrative, and other 4 with destructive pulmonary
      tuberculosis, disseminated and destructive pulmonary tuberculosis occurred in the
      progressive pulmonary sarcoidosis. The etiopathogenetic treatment of tuberculosis
      with at least 3-4 drugs (small-dose hormones, antioxidants, immunomodulators) was
      found to cure the two abnormalities in 95.2% and in 4.8% of cases, the
      pathological process became chronic when limited disseminated pulmonary
      tuberculosis was concurrent with disseminated pulmonary sarcoidosis.

PMID- 9613176
TI  - [External respiratory function in patients before and after saving lung
      resections].
AB  - External respiratory function (ERF) was studied in 129 patients with restrictive
      pulmonary processes (tuberculomas, infiltrative and cavernous tuberculosis)
      before and after surgery. All the patients underwent saving lung resections.
      Changes in ERF were examined by conventional and the new method telespirography.
      This technique detects general and individual pulmonary ventilation disorders,
      which underlie criteria for assessing whether patients with pulmonary
      tuberculosis can be operated on. The authors show that the outcomes of surgical
      treatment are determined by the baseline status of the respiratory apparatus
      generally and each lung specifically. Distinctive features of complicated and
      uncomplicated postoperative periods are identified. The benefits of the new
      method are demonstrated.

PMID- 9613177
TI  - [Efficiency of computed tomography in diagnosis of silicotuberculosis].
AB  - The routine methods X-ray study and computed tomography (CT) were compared in a
      group of patients engaged in fireproof industry. CT yields valuable additional
      data in early silicotuberculosis, which makes it possible to follow the extent of
      a silicotuberculous process more completely, to make a better diagnosis of nodal
      and focal shadows, to identify small decay cavities in the foci and infiltrates.
      CT is the method of choice in following up patients with silicotuberculosis.

PMID- 9613178
TI  - [Secondary immunodeficiency and its myelopid correction in patients with
      infiltrative and disseminated pulmonary tuberculosis].
AB  - The immunity of patients with infiltrative and disseminated pulmonary
      tuberculosis may be characterized as secondary immunodeficiency by the T-cell
      type and neutrophilic phagocytic activity. Myelopid has a stimulating effect on
      the humoral and cellular immunities, restores the baseline reduced functional
      parameters of neutrophilic activity.

PMID- 9613179
TI  - [Impact of specific antituberculosis therapy on gastrointestinal tract in
      children].
AB  - Forty eight children aged 3 to 14 years treated at hospital for various
      tuberculous abnormalities were examined. The findings suggest that the use of
      antituberculosis agents in children with normal acid and pepsin production failed
      to have a noticeable effect on the gastrointestinal tract. Moreover, the 6-month
      use of highly and moderately effective antituberculosis agents produced no effect
      on the aggressive properties of gastric juice. It is necessary to prescribe
      enveloping and mucus-forming agents to reduce the potential side effect of
      tuberculostatic therapy.

PMID- 9613180
TI  - [Adenosine deaminase in differential diagnosis of peripheral lymph node
      tuberculosis].
AB  - Examining the activity of serum adenosine deaminase in 112 patients with
      lymphadenopathy of various etiology revealed its increase (at the discriminant
      level equal or exceeding 20 U/l) in 86% of 50 patients with active tuberculous
      infection. The specificity of the parameter as a test for tuberculous peripheral
      lymph nodal lesion is 90.3%, the positive and negative prognostic significances
      are 83 and 89%, respectively, the diagnostic efficiency is 88.4%.

PMID- 9613181
TI  - [Comparative analysis of two mycobacterium tuberculosis antigens and two
      methodological approaches to determining serum antimycobacterial antibodies].
AB  - The glycoprotein (15-18 kDa) antigen of Mycobacterium tuberculosis H37Rv was
      affinity isolated on the immunosorbent with monoclonal antibodies S4C1G4
      (specific to M. tuberculosis H37Rv; Avdiyenko V. G., Kondrashov S.Yu, Lyashenko
      S.M.@Probl. Tuberk. 1996, v. 1, p. 6-8 (in Russian). This antigen and PPD (Batch
      RT 45, Stattens Seruminstitute, Denmark) that was a standard antigen were used
      for enzyme-linked immunosorbent assay (ELISA), by detecting serum IgG antibodies
      in patients with pulmonary tuberculosis, and control groups of patients with lung
      diseases other than tuberculosis (bronchitis and/or asthma, pneumonia) as well as
      healthy volunteers. The diagnostic parameters of specificity and sensitivity for
      titers and the same parameters for optic density (OD) (in serum dilution with
      maximum differences for groups of patients and donors) were compared. The new
      monoantigen method provided 86.11% specificity and 87.87% sensitivity, which were
      higher those obtained for optic density (63.89 and 80%, respectively). With PPD,
      the specificity and sensitivity were 58.04 and 78.78 (for the new titer method)
      versus 50 and 78.78% (OD data). The method error for titer determination was 10%
      and for standard OD determination was 27%. The new approach offers additional
      possibilities of enhancing the quality of ELISA for diagnosis of tuberculosis.

PMID- 9613182
TI  - [Different sensitivity biochemical mechanisms to mycobacterium tuberculosis of
      guinea pigs and rats].
AB  - Mycobacterium tuberculosis (MT) (H37Rv strain, 0.1 mg) was subcutaneously
      administered to guinea-pigs and rats and 6 weeks later the content of free amino
      acids and oxidized and reduced glutahione were measured in the liver. The guinea
      pigs were found to have higher levels of phosphoethanolamine (PEA), ethanolamine
      (EA), serine, and phenylalanine and lower concentrations of tyrosine. These
      changes are regarded as a sign of damaged cell membranes and impaired redox
      processes in the development of experimental tuberculosis (ET) in guinea-pigs.
      The compensatory adaptation in ET was increased levels of reduced glutathione and
      taurine. In intact rats, the hepatic level of taurine was 5 times higher and that
      of oxidized and reduced glutathione was twice less than in guinea-pigs. Rats did
      not develop ET, in them the level of taurine increased by twice more, that of
      PEA, EA, serine drastically dropped. Species-specific differences in the MT
      sensitivity of guinea-pigs and rats seem to be due to the differences in the
      levels of taurine.

PMID- 9613183
TI  - [Current problems of extrapulmonary tuberculosis].
AB  - There is an overall poor situation due to tuberculosis generally and its
      extrapulmonary involvement specifically. A 2-3-fold rise in the incidence of
      extrapulmonary tuberculosis (EPT) is estimated in the near future. The number of
      patients will total 100,000-120,000. The shortcoming of patients' care is
      associated with poor work organization in all 3 links: detection in the general
      therapeutical network, notification of patients in antitubrculosis dispensaries,
      a reduction in the level of medical care at hospitals, ineffective use of
      interregional hospitals and the clinics of research institutes. Recent years have
      been marked by an extremely alarming situation connected with physicians trained
      in EPT: ageing and natural increase of personnel, no staff training at the
      available bases which have accumulated much experience in practice and
      investigations. To enhance efficiency requires restoration of the whole past
      experience in early detecting, notifying, and treating the patients.

PMID- 9613184
TI  - [Biological features and problems in detection of extrapulmonary tuberculosis
      pathogen].
AB  - The viability, enzymatic activity and Mycobacterium tuberculosis drug resistance
      was compared in pulmonary and extrapulmonary tuberculosis. To decrease oxygen in
      the culture medium baseline values and to use various oxidants as protectors were
      shown to be promising in enhancing the efficiency of cultural diagnosis of
      extrapulmonary tuberculosis.

PMID- 9613185
TI  - [Epidemiological and clinical aspects of extrapulmonary tuberculosis in North
      Western Russia].
AB  - North-western Russia is characterized by poor extrapulmonary tuberculosis (EPT)
      epidemiological trends. There is an increase in the incidence of EPT mainly in
      childhood and youth. Due to incomplete and untimely detection of extrapulmonary
      tuberculosis, the decreased level of recorded parameters and its severe clinical
      pattern are observed in most areas.

PMID- 9613186
TI  - [Evaluation of complex therapy efficiency for urogenital tuberculosis].
AB  - It is most expedient to develop effective modes of improving the etiotropic
      therapy of urogenital tuberculosis, by applying the multipronged approach which
      includes chemoenzyme therapy with native and immobilized terrilytine, enhanced
      activity of basic tuberculostatic agents through their combination with
      nonspecific antibiotics and the use of helium-neon laser, and delivery of drugs
      just to the focus of tuberculous inflammation by endolymphatic injection.

PMID- 9613187
TI  - [Intravascular laser radiation of blood in the multimodality treatment of
      patients with urogenital tuberculosis].
AB  - Laser therapy was performed in 45 patients with tuberculosis of the urinary
      system and male genitals. The radiation was found to have a positive action on
      the patients' general condition and short-term immunomodulating effect. Following
      a month, immunological parameters became baseline or near-baseline. In the course
      of 5 years there was an exacerbation of tuberculosis in 2 (4 +/- 3%) patients who
      had received laser therapy and in 8-18% routinely treated without laser therapy.

PMID- 9613188
TI  - [Tuberculous peritonitis in emergency surgical care].
AB  - The paper presents 5 cases of histologically verified tuberculous peritonitis
      followed up by the author in 1994-1996. All patients were admitted to hospital
      and undergone surgical intervention for emergency indications. The main symptoms
      were intoxication, abdominal pain and enlargement. Two typical cases are
      described. Tuberculous peritonitis is recommended to be included into the
      differential diagnostic list of acute surgical abdominal diseases.

PMID- 9613189
TI  - [Specific features of therapeutical and diagnostic process at the Vyborg-3
      sanatorium under present day socioeconomic conditions].
AB  - The Vyborg-3 republican sanatorium is intended to serve 210 patients with ocular
      tuberculosis. A total of 2521 histories of patients admitted to the sanatorium
      from different regions of the country were examined. A fourth of the patients
      needed differential diagnostic studies. In 9% of patients, the tuberculous
      etiology of eye diseases was excluded. Patients with hematogenic severe and
      complicated ocular tuberculosis are prevalent every year. The proportion of
      complicated forms of ocular tuberculosis (cataract, retinal lesions, uveal
      glaucoma, fibrosis of the vitreous body) is 28%. Therapeutical efficiency in the
      underlying disease is 92%.

PMID- 9613190
TI  - [Conservative and surgical treatment of tuberculosis and other mycobacterium
      infections (lecture)].

PMID- 9613191
TI  - [Value of test therapy in the diagnosis and determination of tuberculosis
      activity in terms of various variants of baseline X-ray pattern of lung
      (lecture)].

PMID- 9613193
TI  - [Mitral valve damage in generalized sarcoidosis].

PMID- 9613192
TI  - [Rare association of mesenteric lymph nodes and gastric mucosa tuberculosis in a
      child].

PMID- 9613194
TI  - Transfusion safety--the Ba Con Study.

PMID- 9613195
TI  - A case of Lactobacillus acidophilus endocarditis successfully treated with
      cefazolin and gentamicin.
AB  - Infective endocarditis secondary to Lactobacillus acidophilus is rare and
      difficult to treat. Management of patients allergic to penicillin is further
      complicated by resistance of Lactobacillus organisms to commonly substituted
      antibiotics. We report a case of a 46-year old woman successfully treated with a
      prolonged course of cefazolin and gentamicin.

PMID- 9613196
TI  - New dosage forms for old anticonvulsants.

PMID- 9613197
TI  - Unexpected requirements for neural induction in the avian embryo.

PMID- 9613198
TI  - A new mechanism broadening the role of prion proteins in neurodegeneration.

PMID- 9613199
TI  - Revolutionary stirrings in Spain.

PMID- 9613200
TI  - News we can use from bacterial chromosomes.

PMID- 9613201
TI  - Conjunction dysfunction: CBP/p300 in human disease.
AB  - CBP and its homolog p300 are large nuclear molecules that coordinate a variety of
      transcriptional pathways with chromatin remodeling. They interact with
      transcriptional activators as well as repressors, direct chromatin-mediated
      transcription, function in TP53-mediated apoptosis, and participate in terminal
      differentiation of certain tissue types. Recent evidence suggests that the demand
      for CBP/p300 is greater than the supply, and that competition for CBP/p300 might
      play an important role in cell growth regulation. Alterations of the human CBP
      gene have been implicated in hematological malignancies as well as in congenital
      malformation and mental retardation. Likewise, the p300 gene has been recently
      implicated in leukemia and mutations in both alleles have been observed in
      gastric and colorectal carcinomas. The role of these proteins in human disease
      coupled with biochemical evidence suggests that CBP and p300 are tumor suppressor
      proteins essential in cell-cycle control, cellular differentiation and human
      development.

PMID- 9613202
TI  - Linear mitochondrial genomes: 30 years down the line.
AB  - At variance with the earlier belief that mitochondrial genomes are represented by
      circular DNA molecules, a large number of organisms have been found to carry
      linear mitochondrial DNA. Studies of linear mitochondrial genomes might provide a
      novel view on the evolutionary history of organelle genomes and contribute to
      delineating mechanisms of maintenance and functioning of telomeres. Because
      linear mitochondrial DNA is present in a number of human pathogens, its
      replication mechanisms might become a target for drugs that would not interfere
      with replication of human circular mitochondrial DNA.

PMID- 9613203
TI  - Putting the brake on drive: meiotic drive of t haplotypes in natural populations
      of mice.
AB  - Mouse t haplotypes are a 'selfish' form of chromosome 17 that show non-mendelian
      transmission from heterozygous +/t males. The considerable transmission bias in
      favour of t haplotypes should result in very high frequencies of these
      chromosomes in natural populations, but they seldom occur at the high frequencies
      expected. Recent research on this and other meiotic drive systems has shown how a
      variety of mechanisms have evolved to suppress drive, and to re-establish
      mendelian segregation.

PMID- 9613204
TI  - Imprinting in Prader-Willi and Angelman syndromes.
AB  - Imprinted genes are marked in the germline and retain molecular memory of their
      parental origin, resulting in allelic expression differences during development.
      Abnormalities in imprinted inheritance occur in several genetic diseases and
      cancer, and are exemplified by the diverse genetic defects involving chromosome
      15q11-q13 in Prader-Willi (PWS) and Angelman (AS) syndromes. PWS involves loss of
      function of multiple paternally expressed genes, while mutations in a single
      gene, UBE3A, which is subject to spatially restricted imprinting, occur in some
      AS patients. Identification of mutations in the imprinting process in PWS and AS
      has led to a definition of an imprinting center (IC), involving the promoter (in
      PWS) or an alternative transcript of the SNRPN gene (in AS). The IC regulates
      initiation of imprint switching for all genes in a 2 Mb imprinted domain during
      gametogenesis. Imprinting mutations define a novel mechanism of genetic disease
      because they have no direct effect in the affected patient but, rather, it is the
      parental germline effect of an IC mutation that leads to disease in the
      offspring.

PMID- 9613205
TI  - Something from nothing: the evolution and utility of satellite repeats.
AB  - Large blocks of tandemly repeated sequences, or satellites, surround the
      centromeres of complex eukaryotes. During mitosis in Drosophila, satellite DNA
      binds proteins that, during interphase, bind other sites. The requirement for a
      repeat to borrow a partner protein from those available at mitosis might limit
      the spectrum of repeat units that can be expanded into large blocks. To account
      for the ubiquity and pericentric localization of satellites, we propose that they
      are utilized to maintain regions of late replication, thus ensuring that the
      centromere is the last region to replicate on a chromosome.

PMID- 9613206
TI  - Unified access to mutation databases.

PMID- 9613207
TI  - It's a knockout!

PMID- 9613208
TI  - [Thoracic trauma--the Achilles heel of the multiple trauma patient].

PMID- 9613209
TI  - [Thoracic trauma].
AB  - Blunt chest trauma is the leading cause of thoracic injuries in Germany,
      penetrating chest injuries are rare. Hereby, single or multiple rib fractures,
      hemato-pneumothorax and pulmonary contusion represent the most common injuries.
      The early management of thoracic injuries consists of detection and sufficient
      therapy of acute life threatening situations like tension pneumothorax, acute
      respiratory insufficiency or severe intrathoracic bleeding. Most of the isolated
      thoracic injuries are adequately treated by conservative means, sufficient
      analgesia, drainage of intrapleural air or blood, physiotherapy and clearance of
      bronchial secretions provided; operative intervention is rarely indicated. In
      multiple injured patients however, severe blunt chest trauma and especially
      pulmonary contusion negatively affects outcome with a significant increase of
      morbidity and mortality. Hence, patients with this combination of pulmonary
      injuries, such as lung contusion and associated severe injuries, carry a
      particular high risk of respiratory failure, ARDS and MOF with a considerable
      mortality. Therefore, early exact diagnosis of all thoracic injuries is essential
      and can be achieved by thoracic computed tomography, which becomes more and more
      popular in this setting. Early intubation and PEEP-ventilation, alternate prone
      and supine positioning of multiple injured patients with lung contusion and
      differentiated concepts of volume- and catecholamine therapy represent the basic
      therapeutic principles. Additionally, the entire early trauma management of
      multiple injured patients must focus on the presence of pulmonary contusion.
      Every additional burden on their pulmonary microvascular system like
      microembolisation during femoral nailing, the trauma burden of extended surgery
      or mediator release in septic states may cause rapid decompensation and organ
      failure and therefore, has to be avoided.

PMID- 9613210
TI  - [Efficacy of ultrasound controlled direct reposition of fragments of the
      posterior vertebral body facet].
AB  - To calculate canal compromise and decrease of midsagittal diameter caused by
      retropulsion of fragments into the spinal canal we analyzed the pre- and
      postoperative computed tomographies of 32 patients with unstable thoracolumbar
      burst fractures treated by USS (universal spine system). Our intention was to
      examine the efficiency of ultrasound guided repositioning of the dispaced
      fragments which was performed in all 32 cases. We found a clear postoperative
      enlargement of canal area (ASP preoperatively 55%, postop. 80%) and midsagittal
      diameter (MSD preop. 58%, postop. 78%). 10 of 13 patients presented a
      postoperative improvement of neurological deficit, no neurological deterioration
      occurred. Fractures with neurological deficit showed more canal compromise (52%)
      and less midsagittal diameter (MSD compromise 51%) than those without (40% or
      39%). There was no correlation between the percentage of spinal canal stenosis
      and the severity of neurological deficit. Below L 1 the spinal canal is greater
      than between Th 11 and L 1, so a more important spinal stenosis is tolerated. In
      case of unstable burst fractures with neurological deficit the ultrasound guided
      spinal fracture reposition is an effective procedure concerning the necessary
      improvement of spinal stenosis: an additional ventral approach for the revision
      of the spinal canal is unneeded. In fractures without neurologic deficit the
      repositioning of the displaced fragments promises an avoidance of long-term
      damages such as myelopathia and claudicatio spinalis.

PMID- 9613211
TI  - [Tensile strength of the tendon of the supraspinatus muscle in the human. A
      biomechanical study].
AB  - The traumatic tear of the rotator cuff has been discussed very intensively for a
      long time despite the fact that there do not exist representative objective data
      about the native tensile strength of these tendons. The aim of this study was to
      evaluate the age related native strength of the supraspinatus tendon. 25 fresh
      frozen cadaver specimen (age: 23-94, 24 h post mortem, 18 male, 7 female) were
      tested using so called cryojaws for soft tissue fixation. The results showed the
      major part of the tensile forces to be transmitted through the anterior thicker
      part of the tendon (e.g. 14 bony avulsions in this area). We found significant
      correlations between age and maximum strength (p < 0.001), age and stiffness of
      the tendon (p < 0.005) and stiffness and maximum strength (p < 0.001). These
      results show that tensile strength and stiffness of the supraspinatus tendon
      decrease with age. However, a 65 year old specimen still demonstrates a weight
      bearing structure (about 900 N maximum tensile strength) and is not necessarily
      ruptured or degeneratively altered.

PMID- 9613212
TI  - [Fracture of the radial condyle of the humerus in the growth period].
AB  - In an overview the clinical and academic problems of this kind of fractures are
      described and their treatment is discussed. The most important problem is the
      pseudarthrosis that can happen in the framework of a conservative treatment of
      displaced fractures, rarely after operative treatment with K-wires. A rather
      academic problem is the obligatory growth disturbance of a partial stimulation of
      the lateral part of the growth plate. This leads to radial overgrowth and thus to
      a more or less distinct varus deformity. The extent of varus deformity is
      dependent on the time till consolidation, which is longest in conservatively
      treated fractures and shortest in those treated with compression screw
      osteosynthesis. An additional academic problem is the so-called fishtail
      deformity that becomes radiological visible at the end of growth. This deformity
      has no clinical significance. Pseudarthrosis, varus and fishtail deformity are a
      result of increasing instability of primarily or secondarily displaced fractures.
      All three problems can be avoided by metaphyseal compression osteosynthesis with
      an AO small-fragment screw with an additional axial K wire in the trochlea. Our
      own long-term results are shown and compared with the results of other procedures
      in the literature.

PMID- 9613213
TI  - [Screw osteosynthesis in dislocated fractures of the radial condyle of the
      humerus in the growth period. A prospective long-term study].
AB  - Pseudoarthrosis and cubitus valgus as main complications following displaced
      fractures of the radial condyle in children can be prevented by open reduction
      and fixation by K wires. However, delayed union and stimulation of the radial
      physis with condylar overgrowth and varisation of the elbow as well as fishtail
      deformities of the distal end of the humerus are reported nevertheless. To
      prevent those growth disturbances all primary and secondary (4-day X-ray control)
      displaced fractures of the radial condyle, i.e. those with a central gap of more
      than 2 mm, were prospectively treated by open reduction and osteosynthesis with a
      metaphyseal lag screw beginning 1974. Sixty-six patients (41 boys, 25 girls) with
      an average follow-up of 10 years (2-22 years) sustained 28 primary and 6
      secondary displaced fractures. In 5 cases a K wire fixation was performed in view
      of the smallness of the fragment. Two children with conservative treatment
      following overlooked displaced fractures showed condylar overgrowth and
      varisation of the elbow. Screw osteosynthesis led to symmetric elbow angles and
      function in all cases, whereas fishtail deformities could be observed in 8 of 27
      children, probably as a consequence of the remaining central fracture
      instability. CONCLUSION: Open reduction and osteosynthesis with a metaphyseal lag
      screw prevents condylar overgrowth in displaced fractures of the radial condyle
      by guaranteeing fracture healing in anatomic position within 3-4 weeks. However,
      fishtail deformity can not be prevented by metaphyseal compression only.

PMID- 9613214
TI  - [Prognosis of proximal radius fractures in the growth period].
AB  - Fractures of the proximal radius in children may lead to deformities of the
      radial head and functional disturbance of pro- and supination. However,
      traumatization is not only caused by the injury itself, but may also occur
      secondary to surgical reduction, manipulation of fracture fragments and excessive
      physiotherapy. In a prospective long-term follow-study (2-20 years after trauma)
      of 38 children with displaced proximal radius fractures we found functional
      disturbances in 11% of children only. These were not caused by radial head
      deformities, which were present on 83% of follow-up radiographs. Functional
      impairment was mainly seen after open reduction or secondary growth disturbances.
      On follow-up radiographs all conservatively treated fracture angulations up to 60
      degrees had corrected themselves spontaneously. In view of the high complication
      rates after open reduction and the poor functional results, as well as the
      inconvenience for the pediatric patient and the economic aspects, we recommend a
      primary conservative treatment concept of proximal radius fractures in children.

PMID- 9613215
TI  - [Treatment of Achilles tendon rupture].

PMID- 9613216
TI  - [Treatment of chronic acetabular pelvic osteomyelitis after alloprosthetic hip
      joint replacement with a gluteus maximus flap].
AB  - We report on a 65-year-old man who was sent to our clinic with osteomyelitis of
      the hip combined with a chronic external fistula after hip joint replacement
      followed by several further operations including amputation of the leg. After
      complete removal of the fistula and repeated vacuum sealing of the wound, we used
      a vasculated glutaeus maximus muscle flap to close the defect. The course after
      the operation was without any complications. The method applied led to sufficient
      treatment of the osteomyelitis without weakening the trunk muscles or rendering
      the use of crutches more difficult.

PMID- 9613217
TI  - [Closed rupture of the tendon of the anterior tibial muscle].
AB  - Closed rupture of the anterior tibial tendon is rare. Fewer than 50 cases have
      been reported in the literature, perhaps because the symptoms are often neglected
      by the patient as well as by the doctor. Most often the rupture occurs as a
      consequence of a sudden plantar flexion of the ankle and pre-existing
      degenerative changes of the tendon tissue due to systemic disease or iatrogenic
      local corticoid injections. Clinically, the tendon rupture presents as acute
      weakness of the ankle extensors without reddening, swelling or neurological
      signs. Differential diagnoses such as anterior tibial syndrome and peroneal nerve
      palsy can thus be excluded. During the clinical examination the distal stump and
      the discontinuity of the anterior tibial tendon are often palpable. The clinical
      diagnosis can be confirmed by an ultrasound examination. An operation may be
      undertaken up to 3 months after the injury. Preferred procedures are end-to-end
      anastomosis and transosseous refixation of the tendon, followed by a plaster cast
      for 6 weeks post-operatively. High-risk patients can be treated conservatively,
      but the functional results are less satisfactory. We describe a case of an acute
      closed rupture of the anterior tibial tendon. A yet unpublished method of osseous
      reinsertion of the tendon is presented.

PMID- 9613218
TI  - [Multidimensional corrective osteotomy of the proximal femur using the gamma
      nail].
AB  - We report on a 57-year-old patient suffering from a complex malposition of
      proximal femur after osteosynthesis using a condylar plate. For polyaxial
      correction of the proximal femur we successfully used an intramedullary hip screw
      system.

PMID- 9613219
TI  - Stress and strain of short haul bus drivers: psychophysiology as a design
      oriented method for analysis.
AB  - Psychophysiological measures offer objective information for workplace design
      according to user requirements. They are, however, rarely applied in industrial
      practice due to weak points from the designer's point of view, such as the
      differentiation of various superimposed stressors, inter-individual differences,
      and the effort required for data acquisition and handling. In this study a set of
      psychophysiological methods was used to analyse bus driver workplaces as a basis
      for redesign, and afterwards to evaluate design improvements. During inner-city
      operation bus drivers are exposed to a particular workload situation, especially
      due to the high density of traffic and bus stops. Their job is characterized by
      highly frequent and often simultaneous task execution, performed with a
      compulsory body posture and under exposure to vibration and noise. To reduce the
      workload related to the equipment and tasks of bus driving, a research project
      was initiated to design a new driver workplace that meets the specific ergonomic
      requirements of the drivers. A detailed workload analysis, consisting of a task
      analysis, a strain analysis derived from ECG measures and an eye movement
      analysis was performed during public bus driving in different cities and with
      different drivers and bus types. Although the results have to be considered as
      somewhat limited owing to the methodological restraints and conditions of a field
      study, they provided valuable guidance for design. A new concept for the driver
      cabin was created based on this database. After installation, this design was
      evaluated by similar psychophysiological measures. Comparison of the pre- and
      post results indicates that the redesigned work station reduced workload levels.

PMID- 9613220
TI  - A psychophysiological investigation of the effects of driving longer-combination
      vehicles.
AB  - Fatigue contributes to driving-related accidents and fatalities. Cardiovascular
      measures such as heart rate and heart rate variability may serve as early
      indicators of fatigue. In the current investigation, 24 professional truck
      drivers drove three truck configurations: single trailer, triple trailer A-dolly,
      and triple trailer C-dolly on a standard route that lasted between 8 and 10 h.
      During the driving session, continuous measures of heart rate were quantified on
      line. In addition to heart rate, two measures of heart rate variability (i.e.
      respiratory sinus arrhythmia and the Traube-Hering-Mayer wave or 0.1 Hz
      oscillation) were derived from the beat-to-beat heart rate. Independent of
      configuration, heart rate increased and the measures of heart rate variability
      decreased during the driving route. Only heart rate statistically differed among
      the configurations. Since heart rate is physiologically linked to metabolic
      output, the results suggest that the observed effect may be due to the physical
      demands required to drive each truck configuration. In support of this
      conclusion, the heart rate effect was consistent with the subjective report of
      task demand. The slowest heart rates were observed while driving the least
      demanding configuration (i.e. single trailer). The fastest heart rates were
      observed while driving the most demanding configuration (i.e. triple trailer A
      dolly).

PMID- 9613221
TI  - Psychophysiological analysis of mental load during driving on rural roads--a
      quasi-experimental field study.
AB  - The objective of this study was the development and validation of an integrated
      measure-assessment approach (driving performance and psychophysiological
      indicators) for the assessment of driving demands of rural road segments as a
      starting point for design. With 31 student test drivers and a selection of six
      study roads, the reactivity of psychophysiological parameters was evaluated based
      on a general model of cognitive-energetic effort regulation according to Hockey
      (1993). The road curvature change rate was introduced as the independent
      variable, which served as a criterion of objective road difficulty. Based on a
      reliability analysis, the longitudinal and cross-sectional stability, especially
      for heart rate (HR) and blink rate (BR) measures, is sufficiently high. Both
      these psychophysiological variables and speed vary as a function of the curvature
      change rate of the rural road segments. The speed parameter differentiates very
      strongly the different curvature change rates. Among the psychophysiological
      indicators, changes in the blink rate almost exactly mirror the level of the
      curvature change rate owing to the fact that the BR decreases almost steadily
      with increasing curvature change rate. Cardiovascular parameters, such as heart
      rate (HR) and heart rate variability (HRV), and skin conductance response (SCR)
      also vary in relation to driving difficulty of road segments, but at levels of
      intermediate curvature other additional road characteristics may also influence
      these measures.

PMID- 9613222
TI  - Changes in cortisol secretion during shiftwork: implications for tolerance to
      shiftwork?
AB  - The present study was conducted to determine the size of changes and the time
      point of those changes in biological rhythms during night-shift and whether they
      are associated with tolerance to shiftwork. The adrenal hormone cortisol has
      frequently been investigated in the field of shiftwork since it follows a
      pronounced circadian variation and has been demonstrated to be affected by night
      work. However, studies are restricted with respect to sample size, number of
      measurements or duration of sampling periods. Therefore, a sample of 24 night
      shift workers was investigated in a cardiac emergency unit for seven nights.
      Saliva samples were collected frequently for determination of cortisol. A total
      of 28 cortisol measurements in each subject were made in order to decide whether
      the circadian rhythm changed, and if so at which time point. A clear reversal of
      circadian function could be observed for the total group (mean cortisol
      concentrations) after the fifth night. However, inspection of individual patterns
      revealed that six out of 24 subjects did not change in circadian function. These
      subjects exhibited lower durations of and less consistency in recovery sleep
      across the following days after night-work. With respect to personality
      dimensions a pattern associated with neuroticism can be observed in subjects
      without appropriate changes in cortisol rhythm. However, owing to the small
      sample size of non-adapters these results are preliminary and should be
      replicated with larger samples. The overall relationship between neuroticism and
      low adaptability has been discussed.

PMID- 9613223
TI  - Performance differences in reaction tasks are reflected in event-related brain
      potentials (ERPs).
AB  - Event-related potentials (ERPs), which can be extracted from the
      electroencephalogram (EEG), are assumed to reflect distinct cognitive processes
      in real time. Hence ERP analysis could be used in cognitive ergonomics as a tool
      to specify, for example, bottlenecks or sources of individual performance
      differences. Such specific results may be helpful to change the tasks or train
      the subjects specifically. In the present exploratory study, the authors
      investigated whether subjects with large spontaneous differences in performance
      accuracy, as defined by their error rates in a speeded binary choice reaction
      task, also differ in the structure of their ERPs. The ten subjects were divided
      post hoc into two groups with relatively low (about 6%) and high (about 20%)
      error rates. While the reaction times were not significantly different for both
      groups, the ERPs revealed clear group differences. First, large differences were
      seen in the late part of the contingent negative variation (late CNV), which is
      assumed to reflect preparatory processes. Subjects with few errors ('GOOD') had a
      large late CNV, while subjects with many errors ('POOR') showed virtually no late
      CNV. Second, the late P300-subcomponent (which is related to response
      identification) was smaller and delayed for POOR compared to GOOD subjects.
      Finally, the ERP shows signs of poor movement control in POOR subjects. The high
      error rate of POOR subjects can hence be explained by: (1) their insufficient
      preparation for the next trial (small late CNV), which impaired response
      identification (small and delayed late P300 subcomponent); and (2) their poor
      movement control. These interpretations have to be regarded as preliminary and
      should be validated with larger groups of subjects. In conclusion, the main
      reasons for the profound performance differences between the groups, namely
      differential preparation and movement control, could be elucidated by ERP
      analysis. A potential ergonomics application of these results is that they
      suggest specific strategies (for example, a preparation and motor control
      training) to improve the performance of POOR subjects in comparable work
      conditions.

PMID- 9613224
TI  - Effects of different stress settings on cardiovascular parameters and their
      relationship to daily life blood pressure in normotensives, borderline
      hypertensives and hypertensives.
AB  - The aim of this study was to compare a traditional stress setting, consisting of
      two mental arithmetic tasks and two Stroop test modifications, and a stress
      setting of varying task demand and decision latitude according to Karasek's job
      strain model, with respect to their feasibility to elicit differences in
      cardiovascular reactivity and recovery in 20 normotensives, 20 borderline
      hypertensives, and 20 non-medicated hypertensives, carefully selected by means of
      World Health Organization criteria. In addition, the relationship between
      laboratory and everyday blood pressure was investigated. All subjects were tested
      under both stress settings in counterbalanced order. Blood pressure was recorded
      both intermittently from the brachial artery (Riva-Rocci) and continuously from
      the finger (Finapres). Heart rate and electrodermal activity were continuously
      measured as well. Furthermore, daily life blood pressure recorded by means of 24
      h ambulatory monitoring during a normal working day served as criterion for the
      re-classification of the blood pressure groups by means of discriminant analysis
      using physiological recordings from baseline, test phases and rest phases. The
      groups did not show significant differences in their reactivity to the various
      mental stressors including the Karasek-model oriented ones but marked differences
      in their behaviour occurred during the 10 min of recovery following each stress
      setting. Both systolic and diastolic blood pressure in hypertensives failed to
      recover during this period. The results also showed the superiority of the
      Finapres method with respect to reflecting the dynamics of physiological recovery
      processes. None of the stress settings showed an advantage in predicting blood
      pressure in daily life. In general, the results question the validity of mental
      laboratory stressors for the prediction of cardiovascular changes in daily life
      but point to a possible role of recovery processes after stress in the
      development of essential hypertension.

PMID- 9613225
TI  - After-effects of human-computer interaction indicated by P300 of the event
      related brain potential.
AB  - After-effects of human-computer interaction (HCI) were investigated by using the
      P300 component of the event-related brain potential (ERP). Forty-nine subjects
      (naive non-users, beginners, experienced users, programmers) completed three
      paper/pencil tasks (text editing, solving intelligence test items, filling out a
      questionnaire on sensation seeking) and three HCI tasks (text editing, executing
      a tutor program or programming, playing Tetris). The sequence of 7-min tasks was
      randomized between subjects and balanced between groups. After each experimental
      condition ERPs were recorded during an acoustic discrimination task at F3, F4,
      Cz, P3 and P4. Data indicate that: (1) mental after-effects of HCI can be
      detected by P300 of the ERP; (2) HCI showed in general a reduced amplitude; (3)
      P300 amplitude varied also with type of task, mainly at F4 where it was smaller
      after cognitive tasks (intelligence test/programming) and larger after emotion
      based tasks (sensation seeking/Tetris); (4) cognitive tasks showed shorter
      latencies; (5) latencies were widely location-independent (within the range of
      356-358 ms at F3, F4, P3 and P4) after executing the tutor program or
      programming; and (6) all observed after-effects were independent of the user's
      experience in operating computers and may therefore reflect short-term after
      effects only and no structural changes of information processing caused by HCI.

PMID- 9613226
TI  - Physiological workload reactions to increasing levels of task difficulty.
AB  - The sensitivity of physiological measures to mental workload was investigated in
      a flight simulator. Twelve pilots had to fly through a tunnel with varying levels
      of difficulty. Additionally, they had to perform a memory task with four levels
      of difficulty. The easiest memory task was combined with the easiest tunnel task
      and the most difficult memory task with the most difficult tunnel task. Between
      the tunnel tasks, subjects had to fly a pursuit task in which a target jet had to
      be followed. Rest periods before and after the experiment were used as a baseline
      for the physiological measures. Mental workload was measured with heart period,
      continuous blood pressure, respiration and eye blinks. Several respiratory
      parameters, heart rate variability, blood pressure variability and the gain
      between systolic blood pressure and heart period (modulus) were scored. All
      measures showed differences between rest and flight, and between the pursuit and
      the tunnel task. Only heart period was sensitive to difficulty levels in the
      tunnel task. Heart rate variability increased when respiratory activity around
      0.10 Hz increased, which occurred often. The modulus was hardly influenced by
      respiration and therefore appears to be a better measure than heart rate
      variability. Among the respiratory parameters, the duration of a respiratory
      cycle was the most sensitive to changes in workload. The time in between two
      successive eye blinks (blink interval) increased and the blink duration decreased
      as more visual information had to be processed. Increasing the difficulty of the
      memory task led to a decrement in blink interval, probably caused by subvocal
      activity during rehearsal of target letters. The data show that physiological
      measures are sensitive to mental effort, whereas rating scales are sensitive to
      both mental effort and task difficulty.

PMID- 9613228
TI  - Frontal midline theta rhythm and eyeblinking activity during a VDT task and a
      video game: useful tools for psychophysiology in ergonomics.
AB  - The necessity of psychophysiological research in ergonomics has gradually been
      recognized in Japan. In this paper, frontal midline theta rhythm (Fm-theta) and
      eyeblinking are recommended as tools in this field, especially for assessing
      workers' attention concentration, mental workload, fatigue, and interest during
      VDT work at the workplace and playing video games at home. In experiment 1, Fm
      theta and eyeblink rates were measured in 10 Japanese abacus experts (Group E)
      and 10 normal students (Group C) during a visual search task with VDT. Memory
      load affected all measures. The amount of Fm-theta appeared more in Group E than
      Group C, but blink rate was lower in Group E than in Group C. As abacus experts
      have such highly developed skills in concentration, the result indicates that the
      amount of Fm-theta would be a good index of attention concentration in VDT
      workers. The second experiment was done with 10 school-aged children as subjects
      during three visual tasks: video game, mental test and animation. Amounts of Fm
      theta and the degree of blink inhibition were maximum while playing the video
      game, which all subjects reported they most preferred, and minimum while watching
      animation, which eight subjects reported to be most boring. An interesting task
      would seem to provoke Fm-theta and inhibit eyeblink activity. From these two
      experiments, Fm-theta and eyeblink rate would appear to be good indices of
      attention concentration and task pleasantness of a mental task using VDT.

PMID- 9613227
TI  - Brain potentials associated with eye fixations during visual tasks under
      different lighting systems.
AB  - The variations of eye fixation related potentials (EFRPs) were examined in two
      tasks under three lighting conditions for assessment of lighting environments.
      Sixteen subjects participated in two tasks; a difficult and an easy reading task
      under three lighting conditions: Spot light (S), General light (G) and Mixed
      light (M). EEG (Oz) and EOG were recorded. EEG epochs time-locked to onset of eye
      fixations were collected at random and averaged separately in two arrays to
      obtain a pair of EFRPs. Two wave forms under the S were similar, although those
      under the G showed the disparity, the largest disparity being in the easy task
      under the G. Under the S, wave forms of EFRPs were stable in the difficult task.
      The amplitude changed with the task load. The results suggested that EFRPs might
      be an index of the work load under lighting conditions.

PMID- 9613229
TI  - Saccadic velocity and activation: development of a diagnostic tool for assessing
      energy regulation.
AB  - The hypothesis was tested that peak velocity of saccadic eye movements in visual
      motor tasks varies with variables related to energy regulation. The hypothesis is
      based on the cognitive-energetical performance model of Sanders. An experimental
      paradigm was developed in which saccadic peak velocity of task-relevant eye
      movements is measured while a choice reaction task is carried out. Confounding
      factors of saccadic amplitude and movement direction were controlled. The task
      was designed in such a way that in each trial subjects performed a target saccade
      towards an imperative stimulus and a return saccade after the manual response
      back to the centre of the screen. For both types of saccades the experimental
      variables were foreperiod duration (short versus long), knowledge of results
      (with versus without), postsaccadic demand (low versus high) and time on task
      (five 30-min intervals). In two experiments, there are main and interaction
      effects of the task variables on peak saccadic velocity. Return saccades are
      slower than target saccades, but not in the case of high postsaccadic demand.
      Knowledge of results increases peak saccadic velocity, but more so for return
      than for target saccades. Time on task leads to a decrease in peak saccadic
      velocity, which is much stronger for return than for target saccades; furthermore
      this effect is more pronounced after short than after long foreperiods. Peak
      saccadic velocity is changed within seconds. The results support the hypothesis.
      Peak saccadic velocity of task related eye movements reflects energy regulation
      during task performance. The paradigm will be developed as a diagnostic tool in
      workload measurement.

PMID- 9613230
TI  - An enquiry into the relationship between activation and performance using
      saccadic eye movement parameters.
AB  - Saccadic eye movement was measured in three studies in a tracking task in which
      increasing stimulus jumping frequency indicates increasing difficulty. In the
      first study, after taking a benzodiazepine 16 subjects showed decreased saccadic
      velocity (activation indicator), but their reaction times and anticipatory
      behaviour (performance indicators) did not parallel this decline, although the
      saccadic amplitudes did. In the second deactivation study 23 subjects worked on
      somewhat boring oculomotor tasks for 2 h and showed the same decrease in saccadic
      velocity but showed almost no performance decline. In the third study a large
      sample of 254 subjects performed the same short tracking task, which offered the
      detailed analysis of the correspondence of the saccadic activation indicator to
      saccadic performance indicators. Almost all correlations were zero correlations.
      Thus, while performance seems to be practically independent of changing
      activation, the latter is dependent upon performance from one moment to the next.
      Stable differences were found between anticipatory and reactive saccades, which
      indicate an immediate change of saccadic velocity when the response mode changes.
      Therefore a reformulation of the relationship between performance and activation
      is proposed. Performance is stabilized by 'concentration' in a two-stage
      regulation process, i.e., it resists changing activation (for example through
      fatigue). In the second stage, the 'effort loop', additional brainstem activation
      is demanded when concentration alone fails to reach the goals that were set by
      the subject for his performance.

PMID- 9613231
TI  - Glissadic saccades: a possible measure of vigilance.
AB  - Eight males and eight females participated in a 60-min visual signal detection
      task requiring saccadic eye movements. The waveforms of saccades were evaluated
      in terms of glissades, slow eye movements in saccade initiation and termination,
      as a function of time-on-task. Saccades were categorized as anticipatory,
      stimulus-elicited, and return saccades; as well as blink-concurrent versus blink
      free. The results showed that, for blink-free saccades, the occurrence of
      glissadic saccades increased with time-on-task for anticipatory and return
      saccades, but not for stimulus-elicited saccades. Likelihood of blink-concurrent
      glissadic saccades did not change over time-on-task. The results suggest that an
      increase in anticipatory and return glissadic saccades over time-on-task may be
      an index of vigilance decrement.

PMID- 9613232
TI  - A comparison of factor analytic methods of obtaining cardiovascular autonomic
      components for the assessment of mental workload.
AB  - The diagnosticity of heart rate for mental workload assessment can be improved
      with an autonomic space model of sympathetic and parasympathetic nervous system
      influences on the heart. Methods of deriving autonomic components to estimate the
      underlying sympathetic and parasympathetic activity needed to identify autonomic
      modes of control for heart period were examined. Alternative factor extraction
      and rotation methods were compared using data from a laboratory study that
      measured the electrocardiogram and impedance cardiogram simultaneously. Principal
      components analysis with varimax rotation was found to validly estimate the
      sympathetic and parasympathetic activity when computed on multiple
      psychophysiological measures obtained from raw EKG data. Use of the method was
      illustrated with single and dual mental arithmetic and second-order compensatory
      manual tracking tasks. Different autonomic modes of control were found for
      divided attention that were not evident in heart period. Uncoupled sympathetic
      activation was indicated for divided attention when the mental arithmetic tasks
      were added to the tracking single tasks, but uncoupled parasympathetic inhibition
      was indicated for divided attention when the tracking tasks were added to the
      mental arithmetic single tasks.

PMID- 9613233
TI  - Heart period variability and respiratory changes associated with physical and
      mental load: non-linear analysis.
AB  - In the investigation of heart rate and heart rate variability, the discrimination
      between mental workload, physical activity and respiration is known to be
      methodologically difficult. At most, heart rate variability measures are more
      likely to be coarse-grained measures with variability confounded by heart rate.
      Moreover, the spectral analysis of heart rate variability shows broad-band
      frequency characteristics, pointing towards non-stationarity or non-linearity.
      From this it is suggested to focus on non-linear dynamic analyses that are
      variance-insensitive. The experimental section of the paper focuses on the
      estimation of two non-linear measures for both heartbeat dynamics and
      respiration, the correlation dimension indicating complexity and the Lyapunov
      exponents indicating predictability. The results indicate that the complexity of
      heart dynamics is related to the type of task and that the predictability of
      heart dynamics is related to the amount of load.

PMID- 9613234
TI  - Highly selective separation of rhodopsin from bovine rod outer segment membranes
      using combination of divalent cation and alkyl(thio)glucoside.
AB  - The micellization process of bovine rod outer segment (ROS) membranes is
      investigated utilizing a series of neutral detergents. It is found that when
      alkyl(thio)glucosides with an appropriate hydrophillic-lipophilic balance (e.g.
      octylthioglucoside) are used in combination with a divalent cation, rhodopsin is
      selectively extracted from ROS membranes at a specific detergent-to-membrane
      ratio. This allows remarkable purification of rhodopsin by a single-step
      solubilization, because the residual membranes are heavily aggregated in the
      presence of divalent cation and are therefore easily sedimented by low-speed
      centrifugation. The absorption spectrum of the supernatant reproducibly exhibits
      an A280/A500 value of 1.6, an excellent value that could rarely be obtained by
      chromatographic purification. The degree of purification also depends on the type
      of divalent cation included in the solubilization solution; specific binding of
      IIB-series cations (Zn2+ and Cd2+) to ROS membranes is suggested to play an
      important role in the solubilization process. The present result represents a
      unique example of selective solubilization of a specific membrane protein from
      highly aggregated membranes.

PMID- 9613235
TI  - Spectral properties of fluorescein in solvent-water mixtures: applications as a
      probe of hydrogen bonding environments in biological systems.
AB  - Although fluorescein is a widely used fluorescent probe in the biosciences, the
      effect of solvent environment on its spectral properties is poorly understood. In
      this paper we explore the use of fluorescein as a probe of the state of hydrogen
      bonding in its local environment. This application is based on the observation,
      originally made by Martin (Chem. Phys. Lett. 35, 105-111, 1975), that the
      absorption maximum of fluorescein undergoes substantial shifts in organic
      solvents related to the hydrogen bonding power of the solvents. We have extended
      this work by studying the spectral properties of the dianion form of the probe in
      solvent-water mixtures. We show that the magnitude of the shift correlates with
      the alpha and beta parameters of Kamlet and Taft (J. Am. Chem. Soc. 98, 377-383;
      2886-2894, 1976), which provide a scale of the hydrogen bond donor acidities and
      acceptor basicities, respectively, of the solvents. In solvent-water mixtures,
      these shifts reflect general effects of the solvents on the hydrogen bonding
      environment of the fluorescein through water-solvent hydrogen bonding and
      specific effects due to fluorescein-solvent hydrogen bonding. Indeed, both the
      absorption and fluorescence properties appear to be dominated by these effects
      indicating that the spectral shifts of the dianion can be used as an indicator of
      its hydrogen bonding environment. We discuss the application of fluorescein as a
      probe of hydrogen bonding in the microenvironment immediately surrounding the
      fluorophore, and we illustrate the effect with reference to the fluorescein
      antifluorescein antibody complex where it appears that antibodies selected during
      the immune response possess binding sites that are increasingly dehydrated and
      hydrophobic.

PMID- 9613236
TI  - Environmental control of the deformability of the DNA double helix.
AB  - The deformability of DNA is of crucial importance in a number of processes and
      interactions, such as its enzymatic recognition, its packaging into chromosomes,
      its interactions with drugs, and the formation of photodimers in it. Here we have
      studied this property by following the formation of excited-state molecular
      complexes (excimers) between adjacent bases of poly(dA-dT).poly(dA-dT) at 20
      degrees C. The force that drives the helix distortion appears to stem mainly from
      charge-resonance interaction. The results indicate that the deformability of the
      helix on the nanosecond time scale is considerable at normal solvent viscosities,
      whereas it is greatly reduced by frictional forces at high viscosities (attained
      through sucrose addition) at which the excimer has a much less favorable
      geometry: the difference in the interaction energies between 1 cP and 58 cP is
      about 6 kcal/mol, a value that is similar to the base stacking energies for the
      undistorted helix. This behavior parallels the modulation by the solvent
      viscosity of the thermally driven motions of the bases of poly(dA).poly(dT),
      which we recently reported on the basis of time-resolved intrinsic fluorescence
      anisotropy measurements (S. Georghiou et al., Biophys, J., 70, 1909-1922, 1996).
      It is inferred that environmental impediments to molecular motion can modulate
      the conformation and dynamics of DNA. Such modulation might play a role in gene
      regulation: particular base configurations, which can be enzymatically
      recognized, may be attained as dictated by the prevailing viscosity conditions
      and/or geometric constraints. By contrast, up to 3 M NaCl or 0.1 M MgCl2 do not
      significantly reduce the deformability of the helix. The considerable plasticity
      of this polynucleotide is probably linked to the significant flexibility of the
      TA step that may account for the wide-spread use of the TATA sequence in
      transcription, site-specific recombination and the initiation of DNA replication.

PMID- 9613237
TI  - The origin of the wavelength-dependent photoreactivity of trans-urocanic acid.
AB  - Two-color, pulsed-laser photoacoustic calorimetry is used to distinguish between
      multiple rotamer or electronic state contributions to the absorption spectrum of
      the epidermal chromophore trans-urocanic acid. The data definitively show that
      the wavelength-dependent photochemistry of trans-urocanic acid results from the
      presence of two distinct, weakly coupled electronic states absorbing between 264
      nm and 310 nm.

PMID- 9613238
TI  - Further characterization of UVB radiation effects on Langerhans cells: altered
      expression of the costimulatory molecules B7-1 and B7-2.
AB  - We have reported previously that low-dose UVB radiation (UVBR, 50-200 J/m2)
      perturbs the antigen-presenting cell (APC) function of murine Langerhans cells
      (LC) by interfering with yet undefined costimulatory signals. In this study, we
      investigated (1) the effects of UVBR on the expression of the costimulatory
      molecules B7-1 and B7-2 on murine LC, (2) the functional consequences of
      defective B7-1 and B7-2 signalling on primary and secondary T-cell responses
      induced by LC and (3) the mechanism by which UVBR interferes with B7-1 and B7-2
      expression. Ultraviolet-B radiation dose-dependently inhibited the culture
      induced upregulation of B7-1 and B7-2 on LC from both UVB-susceptible (UVBs,
      C57BL/6) and UVB-resistant (UVBR, Balb/c) mice and abrogated their capacity to
      stimulate proliferation of naive alloreactive T cells and of the KLH (keyhole
      limpet hemocyanin)-specific T helper (Th)1 clone HDK-1. The UVBR-induced
      suppression of B7-1 and B7-2 on LC and their perturbed APC function were related,
      because exogenous triggering of the B7/CD28 pathway with a stimulatory monoclonal
      antibody (mAb) for CD28 to UVB-irradiated LC partially restored T-cell
      proliferation. Such reconstitution was not observed when the mAb was added to
      killed LC, indicating that the UVBR-induced suppression of APC function was not
      due to lethal effects on LC. Conditioned supernatants from UVB-irradiated
      epidermal cells did not inhibit the functional upregulation of B7-1 and B7-2,
      suggesting that UVBR inhibits B7-1 and B7-2 upregulation by acting directly on LC
      and not by altering LC costimulatory function via release of soluble
      immunosuppressive factors. In conclusion, UVBR distorts the functional expression
      of B7-1 and B7-2 on LC from both UVBS and UVBR mice, thereby contributing to the
      failure of UVB-irradiated LC to stimulate resting alloreactive T cells or KLH
      specific Th1 cells.

PMID- 9613239
TI  - PUVA-induced cell mortality in NCTC 2544 keratinocytes: is it related to the
      microenvironmental properties of the excited states of psoralens?
AB  - The phototoxic effect of psoralen (PSO), 5-methoxypsoralen (5MOP), 8
      methoxypsoralen (8MOP) and 4,5',8-trimetylpsoralen (TMP) has been compared on the
      NCTC 2544 keratinocyte cell line in terms of cell mortality and lipid
      peroxidation. The order of effectiveness for cell photokilling is TMP, 5MOP >>
      8MOP, PSO, whereas a little lipid peroxidation is observed for the four psoralens
      under study. Oxygen-independent membrane damage seem to play a key role in the
      lethal photodamage because the biological effectiveness of the most hydrophobic
      lipid-soluble psoralens, TMP and 5MOP, is about an order of magnitude higher than
      that of the more water-soluble 8MOP and PSO. In relation to this hypothesis, and
      in contrast to 8MOP, TMP is readily extracted from cells by ethyl acetate, a good
      membrane solvent, as shown by GC/MS analysis on cell extracts. The results are
      discussed in terms of the highly microenvironment-dependent photophysical
      properties of psoralens. By the measure of the intracellular psoralen
      concentration, the neutral red uptake and the lipid peroxidation products, this
      work provides evidence that PUVA therapy-mediated cell mortality is a lipid
      peroxidation-independent phenomenon.

PMID- 9613240
TI  - Characterization of endogenous protoporphyrin IX induced by delta-aminolevulinic
      acid in resting and activated peripheral blood lymphocytes by four-color flow
      cytometry.
AB  - Lymphocytes treated with delta-aminolevulinic acid (ALA) can accumulate the
      photoactive, fluorescent heme precursor, protoporphyrin IX (PpIX). With visible
      light illumination, PpIX can be used in photodynamic therapy (ALA-PDT) to kill or
      functionally alter cells. The aim of this study was to characterize the effects
      of ALA and ALA-PDT on resting and activated human peripheral blood T lymphocytes.
      Accumulation of PpIX depends inversely on the rate of its iron-dependent
      conversion into heme. Activated replicating lymphocytes have low intracellular
      iron levels, with corresponding increases in the transferrin receptor (CD71).
      Thus, we expected activated lymphocytes would preferentially accumulate PpIX.
      Using four-color flow cytometry, we examined ALA-induced PpIX levels in T-cell
      subsets of resting and activated human peripheral blood mononuclear cells and the
      relationship between CD71 and PpIX. Peripheral blood mononuclear cells stimulated
      by phytohemagglutinin (PHA) were simultaneously phenotyped for PpIX, CD71 and the
      T-cell markers CD3 and CD4 or CD8. In activated cells treated with 0-6 mM ALA for
      4 h, PpIX fluorescence was maximal at 1 mM ALA. On a single cell basis, there was
      a strong correlation between PpIX accumulation and CD71 expression. The ALA
      treated, PHA-stimulated, CD71+ lymphocytes had an eight-fold greater mean PpIX
      fluorescence than nonactivated, CD71- cells. Approximately 87% of the CD4+ and
      85% of the CD8+ T cells accumulated PpIX. The PpIX levels of CD8+ cells were
      about 5% greater than CD4+ cells. In addition, mixed lymphocyte reaction
      stimulated cells treated with ALA accumulated more PpIX than controls. Thus,
      activated cells preferentially accumulate endogenous PpIX when exogenous ALA is
      administered. Cytotoxicity studies showed that the majority of the activated
      cells following ALA-PDT were killed but resting cells were spared. Also, in
      examining activation markers by flow cytometry the number of cells that were
      positive for activation markers CD38 or CD71 dramatically decreased after ALA and
      light treatment in activated populations. The data suggest a role for ALA-PDT as
      an immunomodulator or photocytotoxic agent targeting activated lymphocytes.

PMID- 9613241
TI  - Biodistribution of Photofrin II and 5-aminolevulinic acid-induced protoporphyrin
      IX in normal rat bladder and bladder tumor models: implications for photodynamic
      therapy.
AB  - Photodynamic therapy (PDT) has been considered as a potential therapy for
      superficial bladder carcinomas. Cutaneous photosensitivity and reduction of
      bladder capacity are the two well-known complications following systemic
      administration of the commonly used photosensitizer, Photofrin II (PII). The
      objective of the present study was to evaluate whether intravesical (i.b.)
      instillation of photosensitizers for PDT of bladder cancer might be a more
      suitable treatment method. Female Fischer rats were utilized to develop
      orthotopic and heterotopic bladder tumor models. Rats bearing orthotopic bladder
      tumors were treated either intravesically or intravenously with graded doses of 5
      aminolevulinic acid (ALA) or PII. Normal rats received the same doses of ALA or
      PII. As well, rats bearing heterotopic tumor were studied for comparison. The
      biodistribution times (times allowed for tissue uptake and bioconversion
      following drug administration) were 2, 4 or 6 h. Porphyrin fluorescence
      intensities within tumor, urothelium, submucosa, bladder muscularis and abdominal
      muscle were quantitated by confocal laser scanning microscopy. Following
      intravenous (i.v.) injection of ALA, tumor protoporphyrin IX (PpIX) levels peaked
      at 4 h and diminished by 6 h. The PpIX ratios of tumor-to-bladder mucosa,
      submucosa and muscle layers were 3:1, 5:1 and 8:1, respectively, 4 h following
      1000 mg/kg ALA injection. After ALA instillation, the optimal biodistribution
      time appeared to be 4 h. Bladder instillation provided comparable tumor labeling
      with the i.v. route, but lost selectivity of PpIX accumulation between tumor and
      normal urothelium. The PpIX ratio of tumor-to-bladder muscularis was 5:1. After
      i.b. instillation of PII, porphyrin fluorescence was detected only within tumor
      and urothelium, while porphyrin fluorescence was mainly located in bladder
      submucosa following i.v. injection. Intravesical administration of ALA or PII
      might be feasible for PDT of superficial bladder cancers.

PMID- 9613242
TI  - Characterization of photodegradation of meta-tetra(hydroxyphenyl)chlorin (mTHPC)
      in solution: biological consequences in human tumor cells.
AB  - The photobleaching of meta-tetra(hydroxyphenyl)chlorin (mTHPC) (irradiation
      wavelength 413 nm) in protein-containing solution was evaluated by decay in
      absorbance in Soret band and in fluorescence (lambda exc = 423 nm, lambda em =
      655 nm). Light exposure resulted in a decrease in absorption throughout the
      spectrum and simultaneous appearance of new absorption bands in the spectral
      region 325-450 nm. The rate of mTHPC photodegradation, followed by decay in
      absorbance, was 15-fold lower than that observed in fluorescence. This fact
      reflects the photobleaching of presumably monomeric, fluorescing species of
      mTHPC. In order to determine the consequences of photobleaching of fluorescing
      mTHPC material on cellular uptake and photocytotoxicity, human HT29 colon
      adenocarcinoma cells were incubated with photobleached mTHPC during 5 h with or
      without following irradiation with the fixed fluence. Surprisingly, but up to the
      time when the fluorescence decreased by 50%, only a slight decrease in
      photocytotoxicity was detected. Either aggregated forms that have been taken up
      undergo intracellular monomerization (but we did not observe increase in
      fluorescence in living cells) or the photodynamic activity is mostly due to
      aggregates. The discrepancy of mTHPC-photodynamic therapy (PDT) effect and
      fluorescence measurements may suggest that aggregated mTHPC plays an important
      role in mTHPC-PDT.

PMID- 9613243
TI  - The effect of static magnetic fields on the photohemolysis of human erythrocytes
      by ketoprofen.
AB  - Ultraviolet irradiation (lambda > 300 nm) of the nonsteroidal anti-inflammatory
      agent ketoprofen (KP, 3-benzoyl-alpha-methylbenzoacetic acid) in aqueous
      solution, pH 7.4, results in heterolytic decarboxylation of the drug to give 3
      ethylbenzophenone (EtBP). Ketoprofen caused the photohemolysis of human
      erythrocytes probably as a result of lipid peroxidation. Application of a static
      magnetic field (250-1500 G) during UV (> 300 nm) irradiation of KP and
      erythrocytes significantly decreased the time required for photohemolysis. This
      observation suggests that KP-induced photohemolysis involves the initial
      generation of a triplet radical pair derived from the reaction of triplet state
      KP (or 3-EtBP) with erythrocyte component(s) probably lipids. The magnetic field
      increases the concentration and/or lifetime of free radicals that escape from the
      radical pair so that the critical radical concentration needed to initiate
      membrane damage and cause cell lysis is reached sooner. Spin-trapping studies
      with 2,6-dibromo-1-nitrosobenzene-4-sulfonate confirmed that the application of
      an external static magnetic field increased the concentration of radicals
      released during the photolysis of either KP or 3-EtBP dissolved in organized
      media such as sodium dodecylsulfate micelles.

PMID- 9613244
TI  - Pharmacokinetics of tetra(m-hydroxyphenyl)chlorin in human plasma and
      individualized light dosimetry in photodynamic therapy.
AB  - The pharmacokinetics of the photosensitizer 5,10,15,20-tetra(m
      hydroxyphenyl)chlorin (mTHPC) was investigated in the plasma of 20 patients by
      absorption and fluorescence spectroscopy. The temporal behavior was characterized
      by a rapid decrease in concentration during the first minutes after intravenous
      injection of 0.15 mg/kg mTHPC. A minimum concentration in the plasma was reached
      after about 45 min. The drug concentration then increased again, attaining a
      maximum after about 10 h, after which it decreased again with a halflife of about
      30 h. Irradiation tests in the oral cavity at different time intervals after the
      injection revealed that the tissue reaction was only partially correlated with
      the mTHPC plasma level. The tissue response was stronger at later drug-light
      intervals (1-4 days) than during the first hours after injection even though the
      mTHPC plasma concentration was higher at the shorter times. Relative mTHPC
      concentrations were also measured in the mucosae of the oral cavity, the
      esophagus and the bronchi of 27 patients by light-induced fluorescence
      spectroscopy using an optical fiber-based spectrometer. These measurements were
      performed prior to photodynamic therapy (PDT), 4 days after injection of the
      photosensitizer. Highly significant linear correlations were found between the
      relative mTHPC concentrations in the mucosae of these three organs. Likewise, the
      plasma levels of mTHPC measured just before PDT were significantly correlated
      with the mTHPC concentrations in the three types of mucosae mentioned above.
      These results indicate that mTHPC plasma levels measured just before PDT can be
      used for PDT light dosimetry.

PMID- 9613245
TI  - Clearing up cosmetic confusion.

PMID- 9613246
TI  - Irradiation: a safe measure for safer food.

PMID- 9613247
TI  - Heading off migraine pain.

PMID- 9613248
TI  - Alzheimer's: few clues on the mysteries of memory.

PMID- 9613249
TI  - Mono: tough for teens and twenty-somethings.

PMID- 9613250
TI  - The crucial, controversial carotid artery. Part I: The artery in health and
      disease.

PMID- 9613251
TI  - B vitamins and the heart: what men can learn from women.

PMID- 9613252
TI  - Parental love in childhood and health in adulthood: is there a link?

PMID- 9613253
TI  - Insect matters.

PMID- 9613254
TI  - I've been using antihistamine tablets for my allergies, but my pharmacist told me
      that an antihistamine nose spray is now available. Should I switch to the spray?

PMID- 9613255
TI  - I heard on the radio that infections can make people fat. Is it true?

PMID- 9613257
TI  - Psychotherapy for adults with attention deficit disorder.

PMID- 9613256
TI  - Addiction and the brain--Part I.

PMID- 9613258
TI  - Alcoholic but abstinent.

PMID- 9613259
TI  - What is social support?

PMID- 9613260
TI  - Guilt and trauma.

PMID- 9613261
TI  - ECT in Texas.

PMID- 9613262
TI  - What is the relationship between stroke and depression?

PMID- 9613263
TI  - Nitrous oxide: time to stop laughing?

PMID- 9613264
TI  - Patient-controlled analgesia: an assessment by 200 patients.
AB  - Two hundred patients completed a questionnaire about their experiences of patient
      controlled analgesia. The questionnaire covered the following topics: pre
      operative information, reasons for pressing and not pressing the button, pain
      relief, side-effects, safety, advantages and disadvantages of patient-controlled
      analgesia, worries associated with its use and control over pain. A high level of
      satisfaction with the device, together with a view that it afforded control over
      pain, emerged from replies to simple, general questions. However, more detailed
      questions revealed side-effects and fears that constrained its use and hence
      patients' ability to control pain. Control is predominantly a feature of the
      professional's view of patient-controlled analgesia, rather than the patient's
      experience of this analgesic technique.

PMID- 9613265
TI  - Requirements for target-controlled infusion of propofol to insert the laryngeal
      mask airway.
AB  - The success rate for insertion of the laryngeal mask airway was assessed in 60
      patients using a target-controlled infusion of propofol. Eleven of 15 patients
      who received a target propofol concentration of 5 micrograms.ml-1 had the
      laryngeal mask inserted successfully within 3 min of induction of anaesthesia.
      Fourteen of 15 patients who received 6 micrograms.ml-1 had successful insertion
      within 3 min and all 15 patients who received 7 micrograms.ml-1 had successful
      insertion within 3 min. Patients who received 8 micrograms.ml-1 had successful
      insertion within 90s of induction of anaesthesia. The increased success rate of
      LMA insertion with the higher target propofol concentrations was achieved without
      major haemodynamic effects in this group of fit patients. However, adverse
      cardiovascular effects may occur with these doses in elderly or unfit patients.
      It is important in individual patients to titrate the target propofol
      concentration to achieve the required clinical endpoint.

PMID- 9613266
TI  - Consent to clinical trials in anaesthesia.
AB  - In order to evaluate satisfaction with, and recollection of, the consent process,
      we sent a postal questionnaire to 204 patients who had taken part in one of six
      clinical trials. Three trials were multicentre commercial studies and three were
      'in house'. The readability of the different patient information sheets was
      compared. Seventy-seven per cent of patients responded, of whom 82% remembered
      having an information sheet. Most (99%) thought this was easy to read and
      understand. Five patients claimed that they had felt pressurised to take part in
      the trials. Nearly all patients (97%) realised that participation was voluntary
      and that other treatment would not be affected; 83% knew they could have changed
      their minds. There were no differences in the response patterns between the
      patients taking part in the different trials although the patient information
      sheets produced by pharmaceutical companies were longer and more complex than the
      'in hospital' variety. We conclude that increasing the amount and complexity of
      information does not alter patient satisfaction. Taken overall, patients were
      content with the way they were approached when asked for consent for clinical
      trials.

PMID- 9613267
TI  - Intrathecal diamorphine for analgesia after caesarean section. A dose finding
      study and assessment of side-effects.
AB  - Eighty women undergoing elective Caesarean section under spinal anaesthesia using
      hyperbaric bupivacaine 0.5% were randomly allocated to receive, in addition,
      intrathecal diamorphine 0.125, 0.25 or 0.375 mg or saline. Postoperative morphine
      requirements, measured using a patient-controlled analgesia system, were reduced
      in a dose-dependent manner by diamorphine. Pain scores were significantly lower
      at 2 and 6 h following the two larger doses of diamorphine. Less supplemental
      analgesia was required intra-operatively if intrathecal diamorphine had been
      given. The incidences of vomiting and pruritus were also dose-related. No
      respiratory rates of less than 14 breath.min-1 were recorded and the incidence of
      oxygen saturation readings less than 95% and 90% did not differ between groups.
      There were no adverse neonatal effects. Intrathecal diamorphine in the present
      study was found to be safe in doses of up to 0.375 mg following Caesarean
      section. However, minor side-effects were frequently observed.

PMID- 9613268
TI  - A change in resistance? A survey of epidural practice amongst obstetric
      anaesthetists.
AB  - Five hundred members of the Obstetric Anaesthetists Association were surveyed
      regarding their technique for identification of the epidural space. Eighty-one
      per cent of the questionnaires were returned completed. Fifty-nine per cent of
      respondents first learned a loss of resistance to air technique, 33.4% to saline
      and 7.4% another technique. Presently, 37.1% and 52.7% use only a loss of
      resistance to air or saline, respectively. Six per cent use both techniques and
      3.2% use other techniques. Twenty-eight per cent taught a loss of resistance to
      air, 57.2% taught a loss of resistance to saline and 12.9% taught both
      techniques. Twenty-three per cent changed from a loss of resistance to air, to a
      saline technique, and 4.2% vice versa. Forty-seven per cent of those using air
      felt that loss of resistance to air was not associated with a clinically
      significant difference in the incidence of accidental dural puncture compared
      with saline.

PMID- 9613269
TI  - Recovery of post-tetanic count and train-of-four responses at the great toe and
      thumb.
AB  - We have studied the recovery of post-tetanic count and train-of-four responses at
      the great toe and thumb accelerographically after the administration of
      vecuronium 0.2 mg.kg-1. Sixty adult patients scheduled for anaesthesia with
      nitrous oxide and isoflurane were studied. The times to the return of the first
      post-tetanic twitch were comparable at the great toe and thumb (mean (SD) times:
      30.0 (6.5) min and 35.0 (8.5) min, respectively). Recovery of post-tetanic count
      followed similar time courses at the great toe and thumb. Also, time to the
      return of the first twitch of the train-of-four did not differ significantly at
      the great toe and the thumb (47.5 (9.6) min vs. 49.7 (10.5) min). Similarly, time
      to the return of the second, third and fourth twitches of the train-of-four did
      not significantly differ at the great toe and the thumb. However, the value of
      the first twitch of the train-of-four, expressed as a proportion of control
      twitch, was significantly higher than that at the thumb between 50 min and 110
      min after the vecuronium injection, and the train-of-four ratio at the great toe
      was significantly higher than that at the thumb between 60 min and 100 min after
      the vecuronium injection.

PMID- 9613270
TI  - Use of the Combitube for airway maintenance during percutaneous dilatational
      tracheostomy.
AB  - The Combitube airway allows short-term ventilation during cardiopulmonary
      resuscitation and can be useful in the management of the difficult airway. In a
      prospective observational study we assessed its use during percutaneous
      dilatational tracheostomy (PDT). Twenty-one intensive care patients scheduled for
      elective PDT had their tracheal tube replaced by a Combitube airway retaining the
      same ventilator settings. Arterial blood gases, airway pressures, SpO2 and end
      tidal CO2 were measured as were the transmural pressures exerted by the Combitube
      cuffs. Combitube placement was successful in 20 of 21 patients although adequate
      ventilation was possible in only 17 (85%). There was no significant change in
      PaO2, SpO2, end-tidal CO2, Paco2 or mean airway pressure during Combitube
      ventilation. A high mean (SD) transmural pressure of 14.7 (5) kPa was exerted by
      the distal cuff. The Combitube provided a satisfactory alternative airway to the
      tracheal tube during performance of PDT in 85% of our patients. Potential
      problems associated with its use in intensive care patients are outlined.

PMID- 9613271
TI  - Evaluation of five oxygen delivery devices in spontaneously breathing subjects by
      oxygraphy.
AB  - Oxygen supply systems may be divided into constant and variable performance
      systems. As the variable performance systems are widely used, it is relevant to
      investigate the variation in performance between devices and the influence of
      oxygen supply on the inspired oxygen fraction. Data were collected from 10
      healthy volunteers during the use of one constant performance system and four
      variable performance systems at different gas flows and inspired oxygen
      fractions. A thin sampling catheter was placed in the nasopharynx to allow the
      measurement of the end-tidal oxygen fraction. When oxygen was supplied to
      variable performance systems, end-tidal oxygen fraction values measured in this
      way varied less and were more easily quantifiable than inspired oxygen fraction.
      End-tidal oxygen fraction was used to calculate inspired oxygen fraction. With
      the variable performance systems, inspired oxygen fraction varied considerably
      between subjects whereas a constant and equal rise was found for each subject
      with the fixed performance system. A large nasal catheter was capable of
      delivering the highest inspired oxygen fraction, whereas the Venturi mask
      delivered the most precise inspired oxygen fraction. We found oxygraphy useful in
      the interpretation of measurements made in patients receiving unknown inspired
      fractions of oxygen.

PMID- 9613272
TI  - The theoretical ideal fresh-gas flow sequence at the start of low-flow
      anaesthesia.
AB  - A spreadsheet model of a circle breathing system and a 70-kg anaesthetised
      'standard man' has been used to simulate the first 20 min of low-flow anaesthesia
      with halothane, enflurane, isoflurane, sevoflurane and desflurane in oxygen. It
      is shown that, with the fresh-gas flow set initially equal to the total
      ventilation and the fresh-gas partial pressure to 3 MAC, the end-expired partial
      pressure can be raised to 1 MAC in 1 min with desflurane and sevoflurane, 1.5 min
      with isoflurane, 2.5 min with enflurane and 4 min with halothane. Sequences of
      lower fresh-gas flow and partial pressure settings are given for then maintaining
      1 MAC end-expired partial pressure, with a minimum usage of anaesthetic, e.g. 13
      ml of liquid desflurane in 20 min (of which only 33% is taken up by the patient)
      if the minimum acceptable flow is 11.min-1, or 8 ml (with 57% in the patient) if
      the minimum is 250 ml.min-1.

PMID- 9613273
TI  - Anaesthesia for chronic spinal cord lesions.
AB  - Increasing numbers of patients with spinal cord injury present for surgery or
      obstetric care. Spinal cord injury causes unique pathophysiological changes. The
      most important peri-operative dangers are autonomic dysreflexia, bradycardia,
      hypotension, respiratory inadequacy and muscle spasms. Autonomic dysreflexia is
      suggested by headache, sweating, bradycardia and severe hypertension and may be
      precipitated by surgery, especially bladder distension. Patients with low,
      complete lesions, undergoing surgery below the level of injury, may safely do so
      without anaesthesia provided there is no history of autonomic dysreflexia or
      troublesome spasms. An anaesthetist should be present to monitor the patient in
      this situation. General anaesthesia of sufficient depth is effective at
      controlling spasms and autonomic dysreflexia but hypotension and respiratory
      dysfunction are risks. There is a growing consensus that spinal anaesthesia is
      safe, effective and technically simple to perform in this group of patients. We
      present a survey of 515 consecutive anaesthetics in cord-injured patients and a
      review of the current literature on anaesthesia for patients with chronic spinal
      cord lesions.

PMID- 9613274
TI  - Pericardial placement of a pulmonary artery catheter.
AB  - Extravascular placement of a pulmonary artery catheter occurred when it was
      passed down an in situ sheath, the side arm of which had already been used for
      administration of fluids without any problems. The case emphasises that
      complications occur with the use of invasive monitoring and a correctly placed
      line may become extravascular even in a short time.

PMID- 9613275
TI  - Bacterial meningitis following combined spinal-epidural analgesia for labour.
AB  - We report a case of Streptococcus salivarius meningitis following combined spinal
      epidural analgesia for labour. Although rare, bacterial meningitis following
      combined spinal-epidural anaesthesia is being increasingly described. We review
      the previously reported cases and discuss the possible aetiological causes and
      the aseptic precautions likely to reduce the incidence of infectious
      complications.

PMID- 9613277
TI  - Prolonged impairment in activities of daily living due to postdural puncture
      headache after diagnostic lumbar puncture.
AB  - To assess the incidence of postdural puncture headache and its effects on
      patients' activities of daily living, we interviewed 325 adult patients subjected
      to a diagnostic lumbar puncture during a 1-year period. Two hundred and eighteen
      (67%) of the subjects replied to the questionnaire; 41 (19%) of these were
      diagnosed as having suffered a postdural puncture headache. Impairment of the
      activities of daily living persisting for 1 week or more was experienced by 16
      (7%) of the subjects.

PMID- 9613276
TI  - Epidural anaesthesia as a method of pre-emptive analgesia for abdominal
      hysterectomy.
AB  - The effect of pre- versus postincisional epidural blockade without the use of
      systemic opioids was investigated in a randomised, double-blind study of two
      groups of 25 patients undergoing abdominal hysterectomy performed under general
      anaesthesia. The first group received, via a lumbar epidural catheter, 0.9%
      saline (16 ml) 15 min prior to surgical incision and 0.5% bupivacaine (15 ml) and
      fentanyl 50 micrograms (1 ml) 15 min prior to skin closure. The second group of
      25 patients received the same amount of bupivacaine and fentanyl 15 min pre
      incision and saline prior to skin closure. Visual analogue pain scores and
      patient-controlled morphine consumption were measured at specified times for 48
      h. We were unable to detect any significant difference in either of the outcome
      measures of the two groups and thus were unable to demonstrate that epidural
      blockade using local anaesthetic and opioid has a pre-emptive effect.

PMID- 9613278
TI  - The effect of ketamine pretreatment on propofol injection pain in 100 women.
AB  - A controlled, randomised double-blind study was performed to compare the prior
      intravenous administration of ketamine 10 mg (1 ml) or 0.9% saline (1 ml) on
      propofol injection pain. One hundred patients of ASA status 1 or 2 presenting for
      gynaecological surgery were studied. Following an initial 5-ml bolus of propofol
      into a dorsal hand vein, 30 s after the treatment, 84% of the saline control
      patients experienced mild or severe pain compared to 26% of those who were given
      ketamine pretreatment (p < 0.05).

PMID- 9613279
TI  - Caudal epidurals: the whoosh test.
AB  - Caudal epidural injection is a simple procedure that carries a low risk of
      complications. The whoosh test (injection of air into the caudal epidural space
      with simultaneous auscultation over the thoracolumbar spine) has been recommended
      as an aid to correct needle placement. A 1-year prospective study, using
      fluoroscopic imaging to identify needle position, was conducted to compare the
      sensitivity and specificity of the whoosh test with that of clinical impression
      alone in assessing correct needle placement in the caudal space. Of 131 patients
      studied, correct needle placement was achieved in 121 on the first attempt (92%).
      Clinical impression alone had a sensitivity of 94% and a specificity of 20%. The
      whoosh test had a sensitivity of 80% and a specificity of 60%. The whoosh test is
      superior to clinical judgment in detecting incorrect caudal needle placement.

PMID- 9613280
TI  - Awareness during total intravenous anaesthesia with propofol and remifentanil.

PMID- 9613281
TI  - Prescribing of opioid analgesia.

PMID- 9613282
TI  - A new method of drug application to the nasal passage.

PMID- 9613283
TI  - Circadian pacemakers.

PMID- 9613284
TI  - Caesarean delivery during cardiac arrest in late pregnancy.

PMID- 9613285
TI  - Gum elastic bougie for difficult double-lumen intubation.

PMID- 9613286
TI  - Comparative trial of spinal needles for caesarean section.

PMID- 9613287
TI  - Residual fluid in the laryngeal mask cuff.

PMID- 9613288
TI  - Selective serotonin reuptake inhibitors.

PMID- 9613289
TI  - Subconjunctival haemorrhage following rapid sequence induction in pregnancy.

PMID- 9613290
TI  - Use of a urethral catheter to remove an upper airway foreign body.

PMID- 9613291
TI  - A potential PCA hazard.

PMID- 9613292
TI  - Anaesthesia for patients with juvenile chronic arthritis (Still's disease)

PMID- 9613293
TI  - Osteomyelitis following epidural analgesia in an immunocompromised patient.

PMID- 9613294
TI  - Pain clinics and liaison psychiatry.

PMID- 9613295
TI  - Clinical utility of EEG parameters to predict loss of consciousness and response
      to skin incision during total intravenous anaesthesia.
AB  - We studied 30 female patients undergoing elective surgery, to assess the
      reliability of electroencephalogram spectral edge frequency and median frequency
      to predict loss of consciousness and movement in response to skin incision during
      total intravenous anaesthesia. Each patient received a different combination of
      propofol (1, 2, 3, 4, 5 or 6 micrograms.ml-1) and sufentanil (0.1, 0.2, 0.3, 0.5
      or 1.0 ng.ml-1) target concentrations for induction of anaesthesia using target
      controlled infusions, assigned randomly. In a logistic regression model, spectral
      edge frequency was a significant determinant of both loss of consciousness (p =
      0.0006) and movement to skin incision (p = 0.0044), whereas for median frequency
      no significant prediction model could be established. The probabilities of 50%
      and 95% no response for spectral edge frequency were 13.4 Hz and 6.8 Hz,
      respectively. The variability of the data limited the predictive value, so that
      spectral edge frequency was a poor predictor and median frequency was no
      predictor of response in the individual patient during total intravenous
      propofol/sufentanil anaesthesia.

PMID- 9613296
TI  - Pre-operative fasting for paediatric anaesthesia. A survey of current practice.
AB  - There has recently been much debate about pre-operative fasting for paediatric
      anaesthesia. There is no consensus about the optimum fasting times for children
      undergoing elective surgery. In order to establish a standard for paediatric pre
      operative fasting times, we undertook a postal survey, targeting members of the
      Association of Paediatric Anaesthetists resident in the United Kingdom and
      Ireland in 1995. One hundred and sixty-three questionnaires were dispatched, 131
      (80%) were returned and 110 (67%) were complete. The results show that the
      following guidelines for duration of fast are acceptable to the majority of
      respondents-neonates: 2 h for clear fluids, 4 h for breast and formula milk;
      infants: 2 h for clear fluids, 4 h for breast milk, 6 h for formula milk and
      solids; children: 2 h for clear fluids, 6 h for milk and solids. We suggest that
      these times be used as guidelines and audited for pre-operative fasting in
      paediatric anaesthesia.

PMID- 9613297
TI  - Body posture during simulated tracheal intubation.
AB  - Seventeen experienced anaesthetists and 15 novices were filmed intubating the
      trachea of a training manikin. Measurements were made of the distance from
      manikin's chin to subject's nose and of the angles at the elbow, the shoulder and
      of the forearm with the horizontal. Trained subjects stood further back (trained:
      median 43 cm, interquartile range 41-56 cm; novices 35 cm, 26-38 cm; Mann-Whitney
      U, p < 0.01), with a straighter arm (trained elbow angle: 108 degrees, 99-121
      degrees; novices': 92 degrees, 88-102 degrees; Mann-Whitney U, p < 0.01). Trained
      subjects tended to hold the laryngoscope closer to the hinge, with a pincer grip;
      novices were more likely to use a full grip of the handle. Trainers should
      consider giving novices explicit instructions on how to stand and how to hold the
      laryngoscope.

PMID- 9613298
TI  - Power spectral analysis of the electroencephalogram during increasing end
      expiratory concentrations of isoflurane, desflurane and sevoflurane.
AB  - We studied the effects of increasing end-expiratory concentrations of isoflurane
      (0.3, 0.6, 0.9, 1.2 vol.%) (n = 12 patients), desflurane (1.5, 3.0, 4.5, 6.0
      vol.%) (n = 12 patients) and sevoflurane (0.5, 1.0, 1.5, 2.0 vol.%) (n = 12
      patients) on power spectral analysis of the electroencephalogram (EEG). Spectral
      edge frequency (SEF), total power (TP) and relative power in the delta, theta,
      alpha and beta band were calculated. EEG changes were very similar within the
      three groups. SEF decreased, TP and relative power in the delta and theta band
      increased, power in the beta band decreased in a dose-dependent fashion with
      comparable regression lines. This indicates that MAC equivalent administration of
      isoflurane, desflurane and sevoflurane in clinically applied dose ranges is
      associated with equipotent EEG suppression.

PMID- 9613299
TI  - The intubating laryngeal mask. Use in failed and difficult intubation.
AB  - The use of the intubating laryngeal mask in three patients is described. In two
      patients for whom tracheal intubation using traditional techniques had failed,
      the intubating laryngeal mask was used to achieve successful tracheal intubation.
      The trachea of one of these patients was subsequently re-intubated for a second
      procedure using the same technique. A third patient with a cervical spine
      fracture whose trachea was electively intubated using the intubating laryngeal
      mask is also presented.

PMID- 9613300
TI  - Evaluation of the HemoCue for measuring intra-operative haemoglobin
      concentrations: a comparison with the Coulter Max-M.
AB  - We compared haemoglobin concentration values obtained using a portable
      haemoglobinometer, the HemoCue, in the operating theatre with the results
      obtained by the Coulter Max-M in the laboratory. Haemoglobin concentrations were
      measured on 52 arterial blood samples obtained from 13 patients during aortic
      surgery, in theatre with the HemoCue and again by the Coulter Max-M. Twenty
      routine samples from the laboratory were also analysed by both methods. There was
      no significant difference between results, with a mean of 10.94 g.dl-1 and 10.90
      g.dl-1 for the HemoCue and Coulter, respectively (p = 0.12, t = -1.99, df = 70).
      The limits of agreement of the two methods (mean difference +/- 2 SD) were -0.37
      and +0.45 g.dl-1. The coefficients of repeatability of the 20 samples analysed in
      duplicate on each device were 0.26 g.dl-1 and 0.33 g.dl-1, respectively. The
      coefficients of variance were 0.74% (HemoCue) and 0.93% (Coulter). With adequate
      training and monitoring, the HemoCue provides comparable haemoglobin results for
      near-patient testing in theatre.

PMID- 9613301
TI  - Anaesthesia and evidence-based medicine.

PMID- 9613302
TI  - Lung fluid and impedance cardiography.
AB  - Serial thermodilution and impedance cardiac output measurements in two critically
      ill patients are presented. Impedance cardiography failed to detect changes in
      cardiac output and provided values lower than those derived from thermodilution.
      Chest X-ray examination and changes in thoracic impedance suggested that these
      two patients had significantly increased extravascular lung water. This failure
      of impedance cardiography is attributed to aberrant electrical conduction though
      the lungs as a result of increased lung fluid that alters the impedance waveform.
      Although reliable when used in normal subjects, impedance cardiography appears
      not to provide accurate measurements in critically ill patients.

PMID- 9613303
TI  - Sequential changes in gas exchange following traumatic fat embolism.
AB  - We present a young man who developed fat embolism syndrome following a fractured
      femoral shaft. By intermittently measuring oxygen saturation with a pulse
      oximeter and varying the inspired partial pressure of oxygen we were able to
      quantify the development of shunt and ventilation/perfusion (V/Q) mismatch over
      the course of his illness. Shunt and low V/Q gradually improved in the week
      following admission but deteriorated following general anaesthesia for nailing of
      the femur.

PMID- 9613304
TI  - Recurrent respiratory depression after total intravenous anaesthesia with
      propofol and alfentanil.
AB  - Since first commented upon by Lamarche in 1984, several cases of recurrent
      respiratory arrest after alfentanil infusions have been reported. In all these
      cases the alfentanil infusions have been used to supplement conventional
      anaesthetic techniques with nitrous oxide and/or inhalational agents and in most
      cases rather high total alfentanil doses have been administered. We have seen two
      cases of severe recurrent respiratory depression in healthy patients after
      relatively minor procedures performed under total intravenous anaesthesia with
      propofol-alfentanil infusions, air-oxygen ventilation and muscle relaxation,
      where the alfentanil doses administered were quite small. These cases are
      presented in detail and compared within a tabulated presentation with the earlier
      published cases of alfentanil-related recurrent respiratory depression.

PMID- 9613305
TI  - Dorsal column function after epidural and spinal blockade: implications for the
      safety of walking following low-dose regional analgesia for labour.
AB  - Walking after regional blockade for labour using low-dose combinations of
      bupivacaine and fentanyl is possible due to the maintenance of lower limb motor
      power. In order to investigate concerns that dorsal column function, important in
      maintaining balance, is impaired after such techniques, clinical assessment of
      lower limb proprioception and vibration sense was evaluated in parturients after
      either low-dose epidural (n = 30) or spinal blockade (n = 30) for labour
      analgesia and compared with spinal anaesthesia (n = 30) for elective Caesarean
      section using a larger total dose of local anaesthetic. Of the patients receiving
      low-dose regional labour analgesia 7% (n = 4) had abnormal dorsal column function
      compared with 97% (n = 29) receiving spinal anaesthesia for Caesarean section (p
      < 0.001). All patients in the Caesarean section group developed lower limb motor
      weakness, compared with only 10% (n = 6) in the low-dose groups (p < 0.001).
      There were no significant differences between the low-dose groups with respect to
      sensory block, motor block or dorsal column function. Overall, 90% of patients
      receiving low-dose bupivacaine/fentanyl regional labour analgesia had both normal
      lower limb motor power and dorsal column function. Assessment of these parameters
      is recommended before allowing patients to walk after low-dose regional
      techniques for labour.

PMID- 9613306
TI  - Pre-oxygenation using face mask or mouthpiece with and without nose clip: patient
      preferences and efficacy.
AB  - We assessed the effectiveness of mouthpieces for oxygenation before induction of
      anaesthesia. In part 1 of the study we asked 52 day case patients whether they
      would prefer mask, mouthpiece, or mouthpiece with nose clip, and which they would
      be willing to use. In part 2 we pre-oxygenated 18 volunteers using each of the
      three methods in a crossover study. We measured time to 90% end tidal oxygen
      concentration (FE'O2), or maximum FE'O2 after 3 min if less than 90%. Of the
      patients surveyed, 20 (39%) preferred mask, 23 (44%) mouthpiece, one mouthpiece
      with nose clip and nine (17%) expressed no preference. Only 88% would be willing
      to use the face mask, but all would accept either the face mask or the mouthpiece
      with nose clip. In part 2 of the study, the mouthpiece alone proved significantly
      worse than the mask or mouthpiece with nose clip. The latter two did not differ
      significantly. Offering the alternative of mouthpiece with nose clip would
      increase patient acceptance of effective pre-oxygenation.

PMID- 9613307
TI  - Comparison of the effect of EMLA and semicircular subcutaneous anaesthesia in the
      prevention of tourniquet pain during plexus block anaesthesia of the arm.
AB  - In 54 patients who were to undergo surgery of the upper extremity in plexus block
      anaesthesia the effect of 5 g EMLA (group E) on tourniquet pain was examined and
      compared with the effect of a semicircular subcutaneous anaesthesia using 10 ml
      0.25% bupivacaine (group B) or 10 ml 1% mepivacaine (group M). Among the patients
      with satisfactory brachial plexus analgesia allowing for surgery (n = 51), the
      incidence of tourniquet pain was not significantly different between groups E, M
      and B. Notably, there was no significant difference in the time of tourniquet
      application. We conclude that topical application of EMLA is as effective as a
      semicircular subcutaneous anaesthesia with mepivacaine or bupivacaine in the
      prevention of tourniquet pain during brachial plexus anaesthesia.

PMID- 9613308
TI  - Postoperative respiratory function in children after abdominal surgery. A
      comparison of epidural and intramuscular morphine analgesia.
AB  - Thirty children undergoing urological and abdominal surgery were entered into a
      randomised trial comparing the effects of epidural and intramuscular morphine on
      postoperative respiratory function. The forced vital capacity and the forced
      expired volume in 1 s were measured before and 6 h after surgery and on each of
      the following seven days. Significant decreases (p < 0.01) in forced vital
      capacity and forced expired volume in 1 s were seen after surgery. After the
      first postoperative day, a gradual recovery in pulmonary function was observed
      but the measured parameters had not returned to their pre-operative control
      values by the end of the study. There were no statistically significant
      differences between the two groups during the study with respect to forced vital
      capacity and forced expired volume in 1 s. The quality of analgesia was better in
      the epidural morphine group than in the intramuscular morphine group. The
      incomplete recovery of pulmonary function suggests that pain is not the only
      cause of postoperative respiratory changes in these patients.

PMID- 9613309
TI  - The acute pain service: effective or expensive care?
AB  - The effect of introducing an Acute Pain Service into a District General Hospital
      was evaluated by conducting an audit of pain, emesis, sleep and satisfaction
      before and after inception. A total of 1518 questionnaires were collected; in
      which surgical patients had been asked to assess their experience pre- and
      postoperatively. The introduction of an Acute Pain Service significantly (p <
      0.0001) improved in-patient perception of pain relief upon return of
      consciousness after anaesthesia and for 2 days postoperatively, when compared
      with the experience before its inception. The incidence of emetic sequelae did
      not increase and both patient satisfaction (p < 0.001) and sleep pattern (p <
      0.05) in hospital were significantly improved. An estimate of the economic
      benefit suggests that the development of Acute Pain Services may be cost
      effective as well as providing an improved quality of service for patients
      undergoing surgery.

PMID- 9613310
TI  - Drug designers in anaesthesia.

PMID- 9613311
TI  - Drug designers in anaesthesia.

PMID- 9613312
TI  - Double cannulation of central veins: multilumen and pulmonary artery catheter
      introducers.

PMID- 9613313
TI  - Are two sides better than one? A simple modification of a stethoscope.

PMID- 9613314
TI  - Cancellation of major surgery due to lack of ITU beds.

PMID- 9613316
TI  - A leak from a three-way tap.

PMID- 9613315
TI  - The use of filters in anaesthetic breathing systems.

PMID- 9613317
TI  - Beware unexplained fluid loss.

PMID- 9613318
TI  - Remifentanil.

PMID- 9613319
TI  - Defective arterial monitoring kits.

PMID- 9613320
TI  - Postdural puncture headache.

PMID- 9613321
TI  - Are pencil point needles safe for subarachnoid block?

PMID- 9613322
TI  - Position of antireflux valves.

PMID- 9613323
TI  - The anti-emetic efficacy of a combination of ondansetron and droperidol.

PMID- 9613324
TI  - A survey of postoperative nausea and vomiting.

PMID- 9613325
TI  - Reshaping the Macintosh blade.

PMID- 9613326
TI  - Cuffed oropharyngeal airway.

PMID- 9613327
TI  - Nitrous oxide cylinders on anaesthetic machines.

PMID- 9613328
TI  - Management of hypoxaemia during one-lung anaesthesia--a suggestion.

PMID- 9613329
TI  - The Portex introducer, the laryngeal mask and the edentulous patient.

PMID- 9613330
TI  - Stylohyoid ligament calcification as a cause of difficult intubation?

PMID- 9613331
TI  - Opening propofol ampoules.

PMID- 9613332
TI  - Measuring up to shoulder pain.

PMID- 9613333
TI  - The art versus the science of medicine. Are clinical practice guidelines the
      answer?

PMID- 9613335
TI  - A young boy with deforming arthropathy.

PMID- 9613334
TI  - Quantifying digital vascular disease in patients with primary Raynaud's
      phenomenon and systemic sclerosis.

PMID- 9613336
TI  - The responsiveness of the Shoulder Disability Questionnaire.
AB  - OBJECTIVE: To evaluate the responsiveness of the Shoulder Disability
      Questionnaire (SDQ). METHODS: The study was conducted within the framework of an
      observational study on shoulder disorders in primary care. After first
      presentation of their complaints to the general practitioner and after one and
      six months, participants completed the SDQ, a single question on functional
      status (FSQ), and an ordinal 11 point scale for the severity of pain (PSS).
      Responsiveness of the SDQ was evaluated compared with that of the FSQ and PSS, by
      calculating responsiveness ratios and by plotting receiver operating
      characteristic (ROC) curves. Recovery according to the patient was used as an
      external criterion for clinically relevant improvement (complete recovery or much
      improved on a six point Likert scale was denoted as clinically relevant
      improvement). RESULTS: A total of 349 consecutive patients with shoulder
      disorders were enrolled in the observational study. Response rates ranged between
      96% and 89%. Responsiveness ratios were slightly higher for the PSS compared with
      the SDQ (2.53 versus 2.22 at one month, 2.24 versus 1.89 at six months). The area
      under the ROC curve was 0.84 for both the SDQ and the PSS, and 0.72 for the FSQ.
      CONCLUSION: The results of this study confirm the responsiveness of the SDQ,
      making it a useful instrument to assess functional disability in longitudinal
      studies.

PMID- 9613337
TI  - Improved functional outcome in patients with early rheumatoid arthritis treated
      with intramuscular gold: results of a five year prospective study.
AB  - OBJECTIVE: To determine whether there is a relation between disease duration and
      functional outcome in patients with rheumatoid arthritis (RA) treated with
      intramuscular sodium aurothiomolate (gold) for five years. METHODS: 440 patients
      with RA were enrolled in a prospective trial of gold treatment. Initial
      demographic details were recorded. Disease activity was assessed at yearly
      intervals using a combination of clinical (pain score, Ritchie articular index,
      duration of morning stiffness) and laboratory (erythrocyte sedimentation rate, C
      reactive protein) parameters. Change in functional status was assessed using the
      health status questionnaire (HAQ). Patients were stratified according to disease
      duration at outset (group 1 = 0-2 years n = 106, group 2 = > 2-5 years n = 93,
      and group 3 = > 5 years n = 235). RESULTS: There were no significant differences
      between the groups at outset. A total of 160 patients completed five years of
      treatment (group 1 n = 44 (42%), group 2 n = 37 (40%), and group 3 n = 79 (34%)).
      Patients in group 1 had a significantly lower HAQ from year 1 to year 5 with a
      mean improvement of 30% at the end of the study (p < 0.001). Neither group 2 nor
      group 3 had a significant change in their HAQ at study end. There were
      significant improvements in all other variables (p < 0.05) in each group apart
      from pain in group 2. CONCLUSION: Patients with early RA have a larger reversible
      component to their HAQ. Only patients with disease duration of up to two years
      have a longlasting improvement in their functional ability after starting
      intramuscular gold treatment.

PMID- 9613338
TI  - Allelic variation in the vitamin D receptor, lifestyle factors and lumbar spinal
      degenerative disease.
AB  - OBJECTIVE: To describe the relation between spinal degenerative disease, allelic
      variation in the vitamin D receptor gene, and lifestyle factors in a population
      based association study. METHODS: Random population-based sample of 110 men and
      172 women over 60 years of age participating in the Dubbo Osteoporosis
      Epidemiology Study who had spinal radiographs (performed according to a
      standardised approach), assessment of lifestyle factors, bone densitometry as
      well as blood taken for genotyping. RESULTS: Spinal degenerative disease of
      varying severity was common in this sample. Multivariate analysis of genetic and
      lifestyle factors simultaneously strengthened the statistical significance of
      each indicating the presence of additive gene environment interaction. Allelic
      variation in the vitamin D receptor gene was associated with severity of
      osteophytosis (adjusted OR "TT" v "tt" 0.41, 95% CI 0.17, 0.97), presence of disc
      narrowing (adjusted OR "TT" v "tt" 0.45, 95% CI 0.20, 0.99) and weakly with
      presence of osteophytosis (adjusted OR "TT" v "tt" 0.47, 95% CI 0.19, 1.16) but
      not with severity of disc narrowing (OR "TT" v "tt" 1.05, 95% CI 0.40, 2.72) or
      apophyseal arthritis (OR "TT" v "tt" 0.63, 95% CI 0.24, 1.59). Adjustment for
      femoral neck bone density did not change these findings suggesting that the
      association is not mediated through bone density. Presence and severity of spinal
      degenerative disease increased with age at all sites. Current smoking increased
      both the presence (adjusted OR 9.70, 95% CI 2.08, 45.1) and severity (adjusted OR
      2.91, 95% CI 1.16, 9.03) of spinal osteophytosis with intermediate values for
      past smokers. Severity of osteophytosis was also independently associated with
      body mass index and quadriceps strength consistent with a contributory effect of
      physical loading. CONCLUSIONS: In this elderly sample, both genetic and lifestyle
      factors were associated with the presence and severity of spinal degenerative
      disease. There were site specific differences in associations at the spine, which
      may be because of misclassification of disease status or may indicate possible
      environmental and genetic differences in the pathophysiology of spinal
      degenerative disease. Further studies are required to confirm these findings in
      different population samples and to further explore potential aetiological
      mechanisms particularly gene environment interaction.

PMID- 9613339
TI  - Analysis of T cell subsets present in the peripheral blood and synovial fluid of
      reactive arthritis patients.
AB  - OBJECTIVE: Reactive arthritis (ReA), a HLA-B27 associated arthropathy, develops
      in susceptible people after infection with certain bacteria. T cells have been
      implicated in the pathogenesis of the arthritis but which of the different
      subsets is involved is still debated. This study has further elucidated the role
      of the CD4+ and CD8+ T cells by examining the expression of various surface
      markers associated with activation. METHODS: Three colour flow cytometry was used
      to examine the phenotype of the T cells within the synovial fluid (SF) and
      peripheral blood (PB) of ReA patients. RESULTS: ReA SF, compared with paired PB,
      contained a higher percentage of CD69+, CD25+, and HLA-DR+ CD3+ T cells. The
      majority of SF T cells also expressed the putative memory marker CD45RO. Within
      the T cell subsets, CD25 was expressed primarily on the CD4+ T cells; however
      more CD8+ T cells were HLA-DR+. CONCLUSION: The results show that both CD4+ and
      CD8+ T cell populations demonstrate evidence of recent activation. Whether these
      cells are involved in inducing inflammation, regulating the inflammation, or have
      become active as a result of migration through the endothelium, remains to be
      determined by functional studies.

PMID- 9613340
TI  - Quality control of synovial fluid crystal identification.
AB  - OBJECTIVE: To establish a quality assessment programme for the diagnosis of
      crystal arthropathies by synovial fluid (SF) microscopy. METHODS: Three or four
      cytocentrifuge slides prepared from suitable patient SF specimens were
      distributed to 25-47 predominantly Finnish clinical laboratories once a year.
      Sodium urate crystals were included in every survey. RESULTS: Returns for the
      years 1989-1996 were reviewed. Laboratories that participated in > four surveys
      made on an average one error a year (range 0.25-2). The error rate for specimens
      containing abundant crystals was acceptable but it increased considerably for
      specimens showing few crystals per microscope field. No laboratory characteristic
      predictive of successful performance was found. CONCLUSION: Errors in quality
      assessment results for crystal identification were much more frequent than in the
      fields of, for example, clinical chemistry or microbiology. Despite efforts to
      provide educational feedback, no improvement was seen during the study period.
      Because of the dearth of data from other parts of the world it is not known for
      certain whether this study has merely pinpointed a local problem or if the same
      trend applies elsewhere.

PMID- 9613341
TI  - Effects of moderate renal insufficiency on pharmacokinetics of methotrexate in
      rheumatoid arthritis patients.
AB  - OBJECTIVES: To determine the effects of impaired renal function on the
      pharmacokinetics of methotrexate (MTX) in rheumatoid arthritis (RA) patients.
      METHODS: 77 RA patients were included in this study. MTX was administered
      intramuscularly (7.5 to 15 mg). Subjects were divided into four groups, according
      to their creatinine clearance (CLCR); group 1: CLCR lower than 45 ml/min; group
      2: CLCR between 45 and 60 ml/min, group 3: CLCR between 61 and 80 ml/min and
      group 4: CLCR higher than 80 ml/min. Blood samples were collected from each
      subject before drug administration and at two and eight hours after
      administration. Individual pharmacokinetic parameters were estimated using a
      Bayesian approach. RESULTS: MTX concentrations (total and free) were 1.3 to 1.6
      times higher in group 1 than in groups 2, 3, and 4. For total and free MTX, t1/2
      eliminations were 22.7 hours in group 1, 13.5 hours in group 2, 12 hours in group
      3, and 11 hours in group 4. Clearance of total MTX was 64, 92, 96, 115 ml/min in
      groups 1 to 4, respectively, it was 118, 163, 171, 206 ml/min in groups 1 to 4
      for the free MTX, respectively. Volume of distribution averaged 2.16 l/kg in
      group 1, 1.92 l/kg in group 2, 1.61 l/kg in group 3, and 1.56 l/kg in group 4.
      Elimination half life was significantly increased and total clearance was
      significantly reduced with the degree of renal impairment. Linear regression
      revealed good correlations between clearance values of MTX and creatinine
      clearance. CONCLUSION: Individual testing is required rather than a general
      decrease of the MTX dose based only on CLCR.

PMID- 9613342
TI  - The diagnostic value of perivascular infiltrates in muscle biopsy specimens for
      the assessment of rheumatoid vasculitis.
AB  - OBJECTIVE: To determine the diagnostic value of perivascular infiltrates (PVI) in
      randomly obtained muscle biopsy specimens for the assessment of rheumatoid
      vasculitis (RV). METHODS: The number and size of PVIs, defined as the presence of
      mononuclear or polymorphonuclear cells around > or = 50% of the circumference of
      a vessel wall, as well as the presence of fibrinoid necrosis were determined in
      frozen sections of muscle samples of RV patients with histologically confirmed
      vasculitis in fixed muscle tissue (n = 12). The findings were compared with those
      observed in frozen sections of muscle biopsy specimens of rheumatoid arthritis
      (RA) patients not suspected of vasculitis (n = 14) and patients with
      osteoarthritis (OA) (n = 11). The presence of PVIs and of fibrinoid necrosis were
      sought in four frozen sections of the muscle biopsy specimen. RESULTS: PVIs were
      observed in 75% of the RV patients, which was significantly (p < 0.05) higher
      than the frequency found in RA (14%) or OA (18%) patients. PVIs with > or = three
      cell layers were found in 67% of the RV patients and in none of the RA and OA
      patients (p < 0.05). Fibrinoid necrosis was found in least one of four frozen
      section in 33% of the RV patients. There was a good intra-observer and inter
      observer concordance on the presence of fibrinoid necrosis and of PVIs with > or
      = three cell layers. CONCLUSIONS: The assessment of PVIs with > or = three cell
      layers in a muscle biopsy specimen is a specific and reliable test in
      discriminating RV from RA without vasculitis. The demonstration in muscle of PVIs
      with > or = three cell layers is more sensitive than that of fibrinoid necrosis
      in the diagnosis of RV.

PMID- 9613343
TI  - Detection of Borrelia burgdorferi by polymerase chain reaction in synovial
      membrane, but not in synovial fluid from patients with persisting Lyme arthritis
      after antibiotic therapy.
AB  - OBJECTIVES: To identify possible sites of bacterial persistence in patients with
      treatment resistant Lyme arthritis. It was determined whether Borrelia
      burgdorferi DNA may be detectable by polymerase chain reaction (PCR) in synovial
      membrane (SM) when PCR results from synovial fluid (SF) had become negative after
      antibiotic therapy. METHODS: Paired SF and SM specimens and urine samples from
      four patients with ongoing or recurring Lyme arthritis despite previous
      antibiotic therapy were investigated. A PCR for the detection of B burgdorferi
      DNA was carried out using primer sets specific for the ospA gene and a p66 gene
      of B burgdorferi. RESULTS: In all four cases, PCR with either primer set was
      negative in SF and urine, but was positive with at least one primer pair in the
      SM specimens. In all patients arthritis completely resolved after additional
      antibiotic treatment. CONCLUSIONS: These data suggest that in patients with
      treatment resistant Lyme arthritis negative PCR results in SF after antibiotic
      therapy do not rule out the intraarticular persistence of B burgdorferi DNA.
      Therefore, in these patients both SF and SM should be analysed for borrelial DNA
      by PCR as positive results in SM are strongly suggestive of ongoing infection.

PMID- 9613344
TI  - Antisense oligonucleotides targeting c-fos mRNA inhibit rheumatoid synovial
      fibroblast proliferation.
AB  - OBJECTIVE: To determine whether antisense oligonucleotides targeting c-fos mRNA
      have the ability to inhibit the growth of interleukin 1 (IL1) stimulated
      fibroblast-like cells from the synovium in rheumatoid arthritis (RA). METHODS:
      Fibroblast-like cells established from RA synovium were stimulated by IL1 with
      antisense or sense oligonucleotides complementary to c-fos mRNA, and the
      proliferation of these cells was determined by 3H-thymidine incorporation. Effect
      of antisense oligonucleotides on expression of activator protein 1 (AP1) activity
      was evaluated using electrophoretic mobility shift assay. RESULTS: C-fos
      antisense oligonucleotides inhibited IL1 stimulated synovial fibroblast
      proliferation. The expression of AP1 activity induced by IL1 was suppressed by
      treatment with antisense oligonucleotides. CONCLUSION: These results suggest the
      feasibility of antisense strategies designed to suppress c-fos expression as
      therapeutic agents for RA.

PMID- 9613345
TI  - Molecular basis of virulence.

PMID- 9613346
TI  - Growing interest in overgrowth.

PMID- 9613347
TI  - Diagnosing Friedreich's ataxia.
AB  - Clinical diagnosis is still of the utmost importance and following our review of
      cases diagnosed using the strict criteria, 100% were homozygous for the
      expansion. However, now that there is a relatively simple direct genetic test,
      the diagnosis can be considered in more unusual cases. Genetic testing has been
      shown to be of value in establishing the correct diagnosis and in directing the
      appropriate screening tests, including cardiological assessment and blood sugar
      estimation. Perhaps the most interesting development following identification of
      the gene is the rapid progress in our understanding of the protein. If, as seems
      likely, it turns out to be a mitochondrial protein involved in iron transport, it
      gives cause for hope of effective treatment.

PMID- 9613348
TI  - Treatment of hyperthyroidism in young people.

PMID- 9613349
TI  - Munchausen syndrome by proxy abuse perpetrated by men.
AB  - Fifteen families are described in which one or more child incurred factitious
      illness abuse as a result of the father's false story and actions. The degree of
      direct physical harm, and the chance of death, was high in those families in
      which the father had Munchausen syndrome or marked somatising disorder. Eleven
      children died and another six survived repetitive smothering or poisoning.
      Although the extent of the risk to children living with a parent who has marked
      somatising disorder is unsure, there must be vigilance on behalf of those
      children.

PMID- 9613350
TI  - Procedures, placement, and risks of further abuse after Munchausen syndrome by
      proxy, non-accidental poisoning, and non-accidental suffocation.
AB  - OBJECTIVES: To investigate outcome, management, and prevention in Munchausen
      syndrome by proxy, non-accidental poisoning, and non-accidental suffocation.
      DESIGN: Ascertainment through British Paediatric Surveillance Unit and
      questionnaires to responding paediatricians. SETTING: The UK and Republic of
      Ireland, September 1992 to August 1994. SUBJECTS: Children under 14 years
      diagnosed with the above. MAIN OUTCOME MEASURES: Placement and child protection
      measures for victims and siblings; morbidity and reabuse rates for victims; abuse
      of siblings; prosecution of perpetrators. RESULTS: Outcome data for 119 with
      median follow up of 24 months (range 12 to 44 months). No previously diagnosed
      factitious disease was found to have been caused by genuine disease. Forty six
      children were allowed home without conditions at follow up. Children who had
      suffered from suffocation, non-accidental poisoning, direct harm, and those under
      5 years were less likely to go home. Twenty seven (24%) children still had
      symptoms or signs as a result of the abuse at follow up; 108/120 were originally
      on a child protection register and 35/111 at follow up. Twenty nine per cent
      (34/118) of the perpetrators had been prosecuted and most convicted; 17% of the
      milder cases of Munchausen syndrome by proxy allowed home were reabused. Evidence
      in siblings suggests that in 50% of families with a suffocated child and 40% with
      non-accidental poisoning there would be further abuse, some fatal. CONCLUSIONS:
      This type of abuse is severe with high mortality, morbidity, family disruption,
      reabuse, and harm to siblings. A very cautious approach for child protection with
      reintroduction to home only if circumstances are especially favourable is
      advised. Paediatric follow up by an expert in child protection should also occur.

PMID- 9613352
TI  - Gastrointestinal symptoms in atopic eczema.
AB  - AIMS: To determine the prevalence of gastrointestinal symptoms in children with
      eczema and the association of such symptoms with the extent of eczema or skin
      prick test results. METHODS: Sixty five children with atopic eczema and a control
      group matched for age and sex were recruited. Their parents completed a
      questionnaire about the children's gastrointestinal symptoms. The children's skin
      was examined; their weight, height, and abdominal circumference were measured;
      and skin prick tests were carried out. RESULTS: Gastrointestinal symptoms,
      especially diarrhea, vomiting, and regurgitation, were more common in the
      children with eczema. Diarrhea appeared to be associated with the ingestion of
      specific foods. Gastrointestinal symptoms were related to diffuse eczema and
      positive skin prick tests to foods. There was no anthropometric differences
      between the patient and control groups. CONCLUSIONS: A gastrointestinal disorder
      is common in children with eczema, especially with diffuse distribution. This may
      be responsible for substantial symptoms and may play a part in the pathogenesis
      of the disease and in the failure to thrive with which it is sometimes
      associated.

PMID- 9613351
TI  - Growth in renal failure: a longitudinal study of emotional and behavioural
      changes during trials of growth hormone treatment.
AB  - Growth and psychological functioning were studied in 30 patients with renal
      failure over a two year period following the offer of growth hormone treatment
      for significant short stature. Parents' concerns about growth decreased
      significantly during the study. Twenty eight parents (93%) accepted growth
      hormone treatment; most (74%) were satisfied with it and would opt for it again
      (89%). The views of these parents were unrelated to growth outcome in their
      child. This suggests that the positive responses were related more to the effort
      to improve growth than to any objective treatment success. In contrast children's
      reduction in concern about growth, satisfaction with treatment (36%), and
      decision to opt for growth hormone again (50%) were all significantly related to
      improvement in growth. Parents' reports of non-compliance increased significantly
      from 41% at 1 year to 91% at 2 years in the group as a whole. No significant
      changes were identified in maternal mental distress and no additional costs to
      the psychological health of the children seem to have resulted from the
      introduction of growth hormone treatment. A group of children was identified who
      accepted treatment but had continued poor growth. These appeared to be at
      particular risk of both physical problems and associated or consequent
      psychological difficulties.

PMID- 9613353
TI  - Human milk IgA concentrations during the first year of lactation.
AB  - AIMS: To measure the concentrations of total IgA in the milk secreted by both
      breasts, throughout the first year of lactation, in a cohort of Gambian mothers
      of infants at high risk of infection. SUBJECTS AND METHODS: Sixty five women and
      their infants were studied monthly from the 4th to 52nd postpartum week. Samples
      of milk were obtained from each breast by manual expression immediately before
      the infant was suckled. Milk intakes were measured by test weighing the infants
      before and after feeds over 12 hour periods; IgA concentrations were determined
      by enzyme linked immunosorbent assay. RESULTS: A total of 1590 milk samples was
      measured. The median (interquartile range) concentration of IgA for all samples
      was 0.708 (0.422-1.105) g/l; that in milk obtained from the left breast was 0.785
      (0.458-1.247) g/l, and that in milk obtained from the right breast was 0.645
      (0.388-1.011) g/l (p < 0.0001). There was no significant change in milk or IgA
      intakes with advancing infant age, but there was a close concordance of IgA
      concentrations between the two breasts, with "tracking" of the output of the left
      and right breasts. There was a significant (p < 0.01) negative correlation
      between maternal age and parity, and weight of milk ingested by infants. During
      the dry season (December to May) the median (interquartile range) IgA
      concentration was significantly higher at 0.853 (0.571-1.254) g/l than during the
      rainy season (June to November), when it was 0.518 (0.311-0.909) g/l (p <
      0.0001). CONCLUSIONS: Sustained IgA secretion is likely to protect suckling
      infants from microbial infection.

PMID- 9613354
TI  - Soluble thrombomodulin and antibodies to bovine glomerular endothelial cells in
      patients with Henoch-Schonlein purpura.
AB  - AIM: To evaluate the clinical significance of soluble thrombomodulin and
      antiendothelial cell antibodies (AECA) in children with Henoch-Schonlein purpura.
      METHODS: Binding of serum AECA to bovine glomerular endothelial cells was
      evaluated by enzyme linked immunosorbent assay, cytotoxicity against glomerular
      endothelial cells by spectrophotometric assay, and soluble thrombomodulin
      concentrations by sandwich enzyme immunoassay. RESULTS: IgA AECA were detected in
      seven of 15 patients with Henoch-Schonlein purpura and nephritis, but were not
      detected in patients without nephritis or in controls. Patients with Henoch
      Schonlein nephritis had raised titres of IgA AECA and serum thrombomodulin;
      severe proteinuria and renal histological changes were associated with raised
      titres of IgA AECA and raised serum thrombomodulin. No subjects had complement
      dependent cytotoxicity against glomerular endothelial cells. CONCLUSIONS: High
      titres of IgA AECA and raised serum thrombomodulin may be clinically useful
      markers of renal involvement in patients with Henoch-Schonlein purpura.

PMID- 9613355
TI  - Mannan binding lectin deficiency and concomitant immunodefects.
AB  - OBJECTIVE: To determine the prevalence of a mannan binding lectin (MBL)
      deficiency in children with increased susceptibility to infections and to
      investigate whether other coexisting immunodeficiencies affecting opsonisation
      are needed to render MBL deficiency clinically significant. PATIENTS AND METHODS:
      343 serum samples were collected from 266 children with repeated infections, a
      single episode of severe infection, or prolonged symptoms relating to infection.
      The concentrations of MBL, immunoglobulin G (IgG), M (IgM), A (IgA), and IgG
      subclasses (IgG1-4) were analysed. RESULTS: MBL deficiency was found in nine
      children (3.2%), seven of whom had repeated infections or a single episode of
      severe infection. In two, initial symptoms and signs suggestive of infection
      eventually led to the diagnosis of an autoimmune disease--Still's disease in one
      and pauciarticular juvenile rheumatoid arthritis in the other. Among the children
      with MBL deficiency and infections, concomitant IgG subclass deficiency was
      detected in five and a transient low level of one or two IgG subclasses in two.
      Prevalence of an IgG subclass deficiency in children with MBL deficiency was
      higher than in those without (56% and 22%, respectively). CONCLUSIONS: MBL
      deficiency alone is not an independent risk factor for infection but may be
      manifested in association with another humoral immunodeficiency affecting
      opsonisation. Among children with MBL deficiency, those with juvenile rheumatoid
      arthritis were overrepresented. This calls for further study.

PMID- 9613356
TI  - Universal hearing screening using transient otoacoustic emissions in a community
      health clinic.
AB  - Since 1993, targeted screening of high risk Camden and Islington babies has been
      carried out in hospital using the transient otoacoustic emission (TEOAE)
      technique and auditory brainstem responses (ABR). Because targeted screening is
      difficult to implement, a community pilot study using TEOAE was started in 1995,
      covering 7% of the resident population. Although uptake has not been above 80%,
      client satisfaction has been high and numbers requiring more detailed tertiary
      assessment have been modest (0.5% of the population screened). A comparison was
      made between the cost of a universal neonatal screen using TEOAE and distraction
      testing at 7 months of age. The neonatal screen would be no more expensive to
      implement universally, even when equipment costs are included. A combination of a
      universal neonatal screen with distraction testing at 7 months for those not
      screened is likely to give 96% coverage of hearing screening in the first year of
      life.

PMID- 9613357
TI  - Prolonged mechanical ventilation as a consequence of acute illness.
AB  - OBJECTIVE: To determine why acutely ill children become dependent upon mechanical
      ventilation and what happens to them. METHODS: A retrospective medical record
      study of all patients aged between 1 month and 16 years from 1983 to 1996 who
      required ventilation for more than 28 days. RESULTS: Forty children were
      ventilated for between 36 and 180 days before discharge or death. Before their
      presenting illness, 13 (33%) were normal, 15 (37%) had documented predisposing
      conditions such as bronchopulmonary dysplasia, and the remaining 12 (30%) had
      diagnoses made after admission. The cause of respiratory failure was central in
      four patients (10%), spinal cord in eight (20%), neuromuscular in 11 (28%), and
      pulmonary in 17 (42%). Severe nosocomial infection requiring treatment with
      intravenous antibiotics occurred in 22. To date, 16 children (40%) have died, and
      10 (25%) remain ventilator dependent. Of the 24 survivors, seven (29%) have
      severe residual neurological deficit. CONCLUSIONS: Increasingly, children are
      surviving intensive care only to remain ventilator dependent and at risk of
      significant comorbidity. This study should inform further debate on why such
      children remain ventilator dependent, and how and where they are managed.

PMID- 9613358
TI  - Management of severe chronic thrombocytopenia in von Willebrand's disease type
      2B.
AB  - Two patients with a long history of unexplained thrombocytopenia, eventually
      diagnosed with von Willebrand's disease (vWD) type 2B are reported. In one
      patient with platelet counts of 80 x 10(9)/l 1-desamino-8-D-arginine vasopressin
      (DDAVP) had a favourable effect during bleeding episodes. The second patient
      received intermediate purity von Willebrand's factor (vWF)/factor VIII
      concentrate (Haemate HS), which helped haemostasis during tooth extraction. It
      increased platelet counts from 15 to 30 x 10(9)/l, whereas platelet transfusions
      produced no increase, nor prevented severe bleeding during abdominal surgery.
      Thus the treatment of vWD type 2B might depend on the degree of thrombocytopenia.
      It is recommended that in patients with mild to moderately decreased platelet
      counts, DDAVP treatment can be tried, whereas in patients with severely decreased
      platelet counts intermediate purity vWF/factor VIII concentrate substitution is
      preferred. In addition, vWD type 2B should be considered in the differential
      diagnosis of any child with chronic thrombocytopenia as the treatment strategy is
      different.

PMID- 9613359
TI  - Obesity in 21-hydroxylase deficient patients.
AB  - OBJECTIVES: To evaluate the natural history and timing of adiposity rebound
      (nadir of body mass index (BMI)) in children with congenital adrenal hyperplasia
      21-hydroxylase deficiency (CYP21). STUDY DESIGN: A retrospective mixed
      longitudinal study. METHODS: Height and changes in body composition (BMI; weight
      (kg)/height2 (m)), triceps and subscapular skinfolds) were analysed in 22 (14
      girls, eight boys) prepubertal patients with CYP21 for whom continuous
      anthropometric data were available for at least seven years. BMI and height SD
      scores were compared at 1, 5, and 10 years of age. Skinfold SD scores were
      compared at 2.5 and 5.5 years. Thirteen children (nine girls, four boys) had
      records available from birth which allowed the estimation of the age at adiposity
      "peak" and "rebound". RESULTS: A significant increase in BMI SD score was found
      at 5 and 10 years compared with those at 1 year. No significant change in height
      SD score was observed at these ages. Triceps and skinfold SD score were increased
      significantly at 5.5 compared with 2.5 years. The "rebound" in BMI SD score took
      place at 1.74 years (range 0.71-4.57) compared with 5.5 years (range 3.5-7.0) in
      the normal UK populations. CONCLUSIONS: Normally growing patients with CYP21
      increased their BMI throughout childhood. Adiposity rebound took place on average
      three years earlier than in the general population. These findings suggest that
      even when well controlled in terms of their disease process, patients with CYP21
      are at risk of obesity, which may have important implications for the evolution
      of reproductive function (polycystic ovaries), diabetes, hypertension, and
      cardiovascular disease in these subjects.

PMID- 9613360
TI  - Juvenile polyposis in a tropical country.
AB  - The clinical profile, malignant potential, and management of 17 children with
      juvenile polyposis (more than five juvenile polyps) were evaluated clinically and
      endoscopically. Colonoscopy and polypectomy were done three weekly until colonic
      clearance was achieved, and thereafter two yearly. All polyps were subjected to
      histological examination. Mean age was 7.7 years, with a male preponderance
      (3:1). Presentation was with rectal bleeding (94%), pallor (65%), stunted growth
      (53%), and oedema (47%), and the mean (SD) duration of symptoms was 33 (27)
      months. None had a positive family history or any congenital anomaly. Two
      children had six polyps up to the transverse colon; the rest had numerous polyps
      all over the colon. All children had juvenile polyps on histology and 10 (59%)
      had adenomatous changes (dysplasia). Total colectomy was done in six for
      intractable symptoms. Colon clearance was achieved in eight after an average 3.4
      polypectomy sessions, and three were still on the polypectomy programme. In
      conclusion, juvenile polyposis is commonly associated with low grade dysplasia.
      Serial colonoscopic polypectomy is effective but colectomy is required for
      intractable symptoms and when clearance of the colon is not possible.

PMID- 9613361
TI  - Sigmoidoscopy in minor lower gastrointestinal bleeding.
AB  - The role of sigmoidoscopic examination in the diagnosis, evaluation, and
      treatment of minor lower gastrointestinal bleeding was investigated. A hundred
      patients with minor rectal bleeding were examined by rigid sigmoidoscopy under
      general anaesthesia between January 1989 and July 1996. Patients who had bleeding
      secondary to infections, anal fissure, or haemorrhoids were excluded from study.
      Patients were reviewed retrospectively according to their diagnosis and
      endoscopic and histopathological findings. Twenty nine of these patients were
      girls and 71 boys; their ages ranged between 8 month and 14 years (mean 7.2
      years). Endoscopic pathological findings were established in 60 patients; 32 had
      rectal polyps, 16 non-specific proctitis, four solitary rectal ulcers, three
      internal haemorrhoids, two ulcerative colitis, two Hirschsprung's enterocolitis,
      and one haemangioma. It is concluded that sigmoidoscopic examination should be
      performed for the diagnosis, prognosis, and choice of treatment in patients with
      minor rectal bleeding and the diagnosis should be confirmed histopathologically.

PMID- 9613362
TI  - A comparison of ultrasonic and mechanical stadiometry.
AB  - AIM: To compare an ultrasonic height measuring device (Gulliver) with mechanical
      stadiometry and the classical "book and tape measure" method. METHODS: Blinded
      duplicate measurements of height were made on each of 14 children by a pair of
      observers using a stadiometer (H) and Gulliver (G). Height was measured on a
      further 18 children by parents and an auxologist using Gulliver and the book and
      tape method (TM), and the results were compared with those obtained with a single
      stadiometry measurement. Finally, measurement of a rigid metal box was made on 10
      occasions by the three methods. RESULTS: In the group of 14 children, the mean
      difference (range) in height (H minus G) was +2.8 cm (+0.5 to +4.55 cm), with H
      giving a systematically higher value in 276 of 280 individual measurements. In
      the group of 18 children, height by H was greater than by G or TM in 47 of 52
      individual measurements. The mean (SD) height of the box by H (61.60 (0.07) cm)
      was greater than by G (60.96 (0.15) cm; p < 0.001) but not TM (61.4 (0.16) cm; p
      > 0.05). G and TM produced three times less reliable estimations of height than
      H, but with a large difference in cost, and there was evidence of systematic
      underrecording of height by 0.5 cm with G. CONCLUSIONS: Stadiometry is precise
      and reproducible, and can detect true changes in height over one month periods in
      mid-childhood, and should remain the standard way of observing growth. The book
      and tape method can produce clinically acceptable quarterly estimations of height
      that can be performed in the home.

PMID- 9613363
TI  - Serum vitamin A and beta-carotene concentrations and renal scarring in urinary
      tract infections.
AB  - OBJECTIVE: To evaluate the role of vitamin A on renal scarring in recurrent
      urinary tract infections (UTIs). DESIGN: Twenty three children with UTIs and
      renal scarring (mean (SD) age 7.3 (3.9) years) and 91 children without renal
      scarring (6.4 (3.4) years) were studied. All the children had serum vitamin A and
      beta-carotene measurements and nutritional evaluation. Renal scarring was
      assessed by technetium-99m dimercaptosuccinic acid (99mTc DMSA) scanning.
      Nutritional status of all the patients was within normal limits and not different
      between the groups. RESULTS: Mean (SD) serum vitamin A and beta-carotene
      concentrations were not significantly different between the patients with and
      without renal scarring (vitamin A 53.2 (22.6)/46.8 (17.0) micrograms/dl and beta
      carotene 232.3 (201.3)/272.4 (86.0) micrograms/dl respectively). However, when
      the patients with renal scarring and with greater than 10% difference among the
      DMSA uptakes of their kidneys (11 cases) were evaluated, a significant negative
      correlation was determined between the serum vitamin A concentrations and the
      magnitude of the difference in uptakes of each kidney. The same relation was not
      true for serum beta-carotene concentrations. CONCLUSION: This study demonstrated
      a relation between serum vitamin A concentrations and magnitude of hypoactivity
      in 99mTc DMSA scanning in kidneys with advanced scarring.

PMID- 9613364
TI  - Thrombocytopenic purpura as adverse reaction to recombinant hepatitis B vaccine.
AB  - Three cases of immune thrombocytopenic purpura after the first dose of
      recombinant hepatitis B vaccine occurred in infants under 6 months of age. Other
      possible causes of this condition were excluded. Antiplatelet antibodies were
      present. A defect in platelet production was excluded in two children.
      Corticosteroid treatment was effective. Subsequent administration of other
      vaccines (against polio, diphtheria, and tetanus) did not cause relapse of
      thrombocytopenia.

PMID- 9613365
TI  - Teaching and learning in a neonatal intensive care unit.

PMID- 9613367
TI  - Patent arterial duct: when should it be closed?

PMID- 9613366
TI  - Advances in endocrinology.
AB  - Molecular genetics will continue to help us to make precise diagnoses. At
      present, the expertise to achieve this for a specific disease is often exclusive
      to one unit with a research interest. It will be important to establish a
      coordinated approach at a supraregional level to provide molecular diagnosis for
      rare disorders as a fast reliable clinical service. In addition understanding the
      molecular mechanisms of disease is likely to direct a search for new treatments.
      For instance, calcium channel blockers have been used in nesidoblastosis to
      reduce the hypersecretion of insulin, as a result of the recognition of the role
      that calcium has in the function of the beta-cell ATP sensitive K+ channel.
      Although the potential benefits of hGH are now being clearly defined in a range
      of growth disorders, the treatment is invasive and expensive. It is likely that
      future endocrine therapeutic developments could include slow release growth
      hormone preparations, orally active growth hormone mimetics, or even hormone
      production from an ectopic viral cDNA vector. The next "advances in
      endocrinology" will also reveal whether leptin will have a therapeutic role in
      appetite control or even the modulation of pubertal development.

PMID- 9613368
TI  - Neural tube defects and zinc.

PMID- 9613369
TI  - Integrated management of childhood infections and malnutrition.

PMID- 9613370
TI  - Head lice in children.

PMID- 9613371
TI  - Is botulinum toxin helpful in squint management?

PMID- 9613372
TI  - Growth factors in proliferative vitreoretinopathy.

PMID- 9613373
TI  - Corneal transplantation for herpes simplex keratitis.

PMID- 9613374
TI  - Retreatment of children after surgery for acquired esotropia: reoperation versus
      botulinum injection.
AB  - AIMS: Two viable options were compared, reoperation and botulinum toxin
      injection, in the management of children who need retreatment after surgery for
      acquired esotropia. METHODS: 47 strabismic children previously operated to
      correct an acquired esotropia were randomised to reoperation or botulinum toxin
      injection. Reoperation was undertaken in 24 of these patients and botulinum toxin
      injection in 23 of them. The percentage net change in distance deviation, the
      percentage of patients with successful motor outcome, detectable fusion, and
      stereopsis were compared 1 year after retreatment and at last visit (average
      follow up: 2.9 years in reoperation group, and 2.7 years in botulinum group). The
      motor success rate relative to time elapsed from initial surgery was evaluated.
      RESULTS: There was no significant difference in the motor and sensory outcomes
      between patients reoperated and treated with botulinum injection. The frequency
      of correction to within 8 prism dioptres of orthotropia was, respectively: 75%
      versus 69.56% at 1 year; 70.83% versus 60.86% at last visit. Botulinum injection
      could be more effective when performed within 3 months of initial surgery.
      CONCLUSIONS: Botulinum injection is a rapid and safe procedure that may be as
      effective as reoperation in the management of children who need a secondary
      procedure after surgery for acquired esotropia.

PMID- 9613375
TI  - Effects of acupuncture on foveation characteristics in congenital nystagmus.
AB  - AIMS/BACKGROUND: To examine the effects of acupuncture at the sternocleidomastoid
      muscles on foveation characteristics in congenital nystagmus. METHODS: Six
      patients with congenital nystagmus (CN) received a series of treatments
      consisting of two needles inserted into each sternocleidomastoid, stimulated by
      tapping gently every 5 minutes, for 20 minutes per session. Their eye movements
      were recorded using scleral search coils and changes in their CN waveforms
      analysed at each point in the treatment. Changes in the stability and duration of
      foveation periods were examined. RESULTS: Four of the six patients showed
      improved foveation at the commencement of treatment; three maintained this
      response throughout the treatment period and after the needles were removed. In
      two, the CN waveform itself was modified. CONCLUSION: This study and others
      involving afferent stimulation to the neck and face suggest that projections from
      these areas to the reticular formation and vestibular nucleus may alter the
      behaviour of the pathophysiological mechanism underlying congenital nystagmus.

PMID- 9613376
TI  - Scanning laser tomography Z profile signal width as an objective index of macular
      retinal thickening.
AB  - AIMS: (i) To evaluate the relation between retinal thickness and the Z profile
      signal width of a scanning laser tomographer in selected patients exhibiting
      clinically manifest and circumscribed macular retinal thickening; (ii) to compare
      the Z profile signal width values of a group of age similar normal subjects with
      those of the patients with macular retinal thickening; and (iii) to present the
      methodology underlying the Z profile signal width derivation. METHODS: Three
      patients with the following conditions were selected: widespread diabetic macular
      oedema; localised diabetic macular oedema; and macular hole. The patients were
      selected because they exhibited clinically manifest and circumscribed macular
      retinal thickening. Patients underwent fundus photography and a clinical
      examination which included fundus biomicroscopy. Fourteen age similar normal
      subjects were also assessed. The Heidelberg retina tomograph (HRT) was utilised
      to acquire seven topographic images of each macula. Z profile signal width data
      were analysed using custom software. Signal width was measured at 50% of the
      maximum intensity. RESULTS: For each patient with macular retinal thickening, Z
      profile signal width analysis (after normalisation to reduce the influence of
      variation in reflectance intensity between successive images) revealed a
      significant (p < 0.0001) localised increase of signal width which agreed with the
      HRT topographic analysis of retinal height, and also the clinical assessment of
      retinal thickness. The mean normalised Z profile signal width for the normal
      subjects (assessed over the whole image) ranged from 0.278 (SD 0.039) to 0.444
      (0.063); these values compared with those obtained from patients in areas of
      macular retinal thickening of 0.761 (0.224) to 0.953 (0.194). Z profile signal
      width test-retest data for the patient with localised diabetic macular oedema
      were plus or minus 0.159 which compared with a mean signal width value of 0.761.
      CONCLUSION: The evidence of this study, based upon three selected patients with
      macular retinal thickening and 14 normal subjects, would suggest that Z profile
      signal width analysis offers a non-invasive, objective, topographic, and
      reproducible index of macular retinal thickening. Studies employing larger sample
      sizes are required to determine the true clinical worth of the technique.

PMID- 9613377
TI  - Heidelberg retinal flowmetry: factors affecting blood flow measurement.
AB  - AIMS: To evaluate factors affecting Heidelberg retinal flowmeter (HRF)
      measurements of retinal and optic nerve head blood flow in human subjects.
      METHODS: The angle of incidence between laser beam and fundus, and camera
      distance from the eye, were evaluated for their effect upon measures of blood
      volume, velocity, and flow in a single 100 x 100 x 400 microns volume of temporal
      peripapillary retinal tissue in normal volunteers. Both intra and intersession
      reproducibility of these measures were studied. Intersession data were obtained
      by taking one image per week for 4 weeks. Finally, the intersession haemodynamic
      data were examined in the entire image (640 x 2560 x 400 microns), using
      histograms of pixel by pixel blood flow. RESULTS: Measures of blood volume,
      velocity, and flow from a single anatomical site were unaffected by laser beam to
      fundus angle of incidence (n = 12). As camera distance from the eye was increased
      (from 2 to 5 to 7 cm), flow measurements showed increasing individual changes,
      despite unaltered measured vessel lengths and constant overall mean flow (n =
      14). The coefficient of variation for two intersession images of optic nerve head
      blood flow averaged 7% (n = 20); in contrast, the 4 week intersession coefficient
      of variation averaged 30% (n = 15). Intersession reproducibility was increased by
      using flow histograms from the entire image: the coefficients of variation
      averaged 16% for total flow and 17% for flow in the pixel of median flow.
      CONCLUSION: HRF measures of flow are independent of the laser beam to fundus
      angle of the incidence and dependent upon camera distance from the eye.
      Intersession reproducibility is best using pixel by pixel analysis of the entire
      image.

PMID- 9613379
TI  - Randomised, controlled trial of spirometric changes in elderly people receiving
      timolol or betaxolol as initial treatment for glaucoma.
AB  - AIM: To investigate respiratory and cardiovascular side effects in elderly people
      in the first 12 months after commencing topical beta antagonists. METHODS: 40
      patients (mean age 74 years) were recruited to a randomised, masked study.
      Spirometry, pulse, and blood pressure were recorded before, 1 month, and 12
      months after starting topical therapy with either timolol 0.5% twice daily or
      betaxolol 0.5% twice daily. RESULTS: After 1 month five of 20 patients allocated
      timolol and three of 20 given betaxolol had discontinued it for respiratory
      reasons, not always accompanied by symptoms. There were no significant
      differences in changes in mean values of spirometry, pulse, or blood pressure
      between groups. No further changes were made in therapy for respiratory reasons
      in the following year. One patient suffered a hypotensive stroke within 2 days of
      starting timolol. CONCLUSIONS: By performing spirometry before starting topical
      beta antagonist therapy and repeating it after 1 month most patients at risk of
      respiratory impairment can be identified.

PMID- 9613378
TI  - Antimicrobial management of presumed microbial keratitis: guidelines for
      treatment of central and peripheral ulcers.
AB  - AIMS: To determine the quantitative relation between the major risk factors for
      microbial keratitis of previous ocular surface disease and contact lens wear and
      central and peripheral infiltration, often associated with ulceration, in order
      to establish a rational chemotherapeutic management algorithm. METHODS: Data from
      55 patients were collected over a 10 month period. All cases of presumed
      microbial keratitis where corneal scrapes had been subjected to microbiological
      examination were included. Risk factor data and laboratory outcome were recorded.
      Antimicrobial regimens used to treat each patient were documented. RESULTS: 57
      episodes of presumed microbial keratitis were identified from 55 patients, 24
      male and 31 female. There were 30 central infiltrates and 27 peripheral
      infiltrates of which 28 were culture positive (73% of central infiltrates, 22% of
      peripheral infiltrates). 26 patients had worn contact lenses of whom 12 had
      culture positive scrapes (9/14 for central infiltrates, 3/12 for peripheral
      infiltrates). 31 patients had an ocular surface disease of whom five previous
      herpes simplex virus keratitis patients developed secondary bacterial infection.
      Anterior chamber activity and an infiltrate size > or = 4 mm2 were more common
      with culture positive central infiltrates than peripheral infiltrates (chi 2 test
      = 11.98, p < 0.001). CONCLUSIONS: Predisposing factors for "presumed" microbial
      keratitis, either central or peripheral, were: ocular surface disease (26/57 =
      45.6%), contact lens wear (26/57 = 45.6%), and previous trauma (5/57 = 8.8%).
      Larger ulceration (> or = 4 mm2) with inflammation was more often associated with
      positive culture results for central infiltration. None of these four variables
      (contact lens wear, ocular surface disease, ulcer size, anterior chamber
      activity) were of intrinsic value in predicting if a peripheral infiltrate would
      yield identifiable micro-organisms. Successful management of presumed microbial
      keratitis is aided by a logical approach to therapy, with the use of a defined
      algorithm of first and second line broad spectrum antimicrobials, for application
      at each stage of the investigative and treatment process considering central and
      peripheral infiltration separately.

PMID- 9613380
TI  - Nd:YAG laser iridotomy in pigment dispersion syndrome: an ultrasound
      biomicroscopic study.
AB  - AIMS: Ultrasound biomicroscopy was used to study the shape of the iris and the
      iridolenticular contact in pigment dispersion syndrome (PDS) eyes, to compare
      them with matched normal eyes, and to assess the morphological effects of laser
      iridotomy in PDS eyes. METHODS: 50 eyes of 50 patients suffering from PDS (group
      1), and 15 normal eyes of 15 subjects matched for age and refraction (group 2),
      were studied by ultrasound biomicroscopy (UBM, Humphrey-Zeiss). Nd:YAG laser
      iridotomy was proposed to the 30 PDS patients with concave iris and 18 underwent
      the treatment. RESULTS: The iris was concave in 27 eyes in group 1, and three
      more eyes showed a concave iris during accommodation. Among normals, iris
      concavity was present in two eyes. The height of the iris convexity was -0.15
      (0.24) mm (range -0.65 to +0.21), in the eyes of group 1, whereas it was +0.07
      (0.10) mm (range -0.21 to +0.16) in group 2 (p < 0.0012). Group 1 had greater
      iridolenticular contact than group 2: 1.55 (0.78) mm (range 0.30-2.88) and 1.07
      (0.61) (range 0.30-2.50; p = 0.0304). After laser iridotomy, only one eye still
      had a concave iris. Pre- and post-treatment deflections were -0.35 (0.18) mm
      (range -0.61 to -0.05) and +0.01 (0.06) mm (range -0.12 to +0.17), respectively
      (p < 0.0001). Pre- and post-treatment iridolenticular contact was 2.10 (0.65) mm
      (range 0.70-2.88) and 0.93 (0.38) mm (range 0.4-1.75), respectively (p < 0.0001).
      After laser iridotomy, the treated irises were flatter than normal (p = 0.0207),
      whereas the iridolenticular contact was not significantly different. CONCLUSIONS:
      Laser iridotomy can restore a normal iris shape and iridolenticular contact in
      eyes suffering from PDS.

PMID- 9613381
TI  - Echographic findings in uveal melanomas treated with the Leksell gamma knife.
AB  - BACKGROUND/AIMS: Between June 1992 and July 1995, 29 uveal melanomas were treated
      radiosurgically with the Leksell gamma unit at the University of Graz. The aim of
      this retrospective study was to examine the pattern of regression and the extent
      and time period of the decrease in tumour size. METHODS: The Leksell gamma knife,
      model B, was used. Patients were divided into three groups according to marginal
      dose: group 1: eight patients with a marginal dose > 50 Gy, group 2: 15 patients
      with a marginal dose = 50 Gy, and group 3: six patients with a marginal dose = 45
      Gy. For the retrospective study two groups were examined: group A, tumours < 5 mm
      and group B, tumours > or = 5 mm. RESULTS: No significant correlation was found
      between tumour regression and the marginal dose. Tumour shrinkage depends on the
      pretreatment height. In the group of eight patients with an initial tumour
      prominence of less than 5 mm, no prominence was found after therapy. In the group
      of patients with an original tumour prominence of 5 mm and more, only two tumours
      formed a flat scar while a residual prominence was found in 18 patients. Increase
      in reflectivity combined with a decrease in size appears to be a good criterion
      for the effectiveness of the treatment. In five patients with tumours showing low
      reflectivity, over a longer period of time metastases were found. An enucleation
      was performed in two patients because of uncertain tumour regression and in one
      patient as a result of an increase in tumour size. CONCLUSION: The pattern of
      echographic reflectivity and decrease in size is similar to brachytherapy and is
      one of the most important diagnostic variables for evaluation of tumour
      regression. An increase in reflectivity as well as a decrease in tumour size in
      the first 6-8 months can be considered a therapeutic success.

PMID- 9613382
TI  - Choroidal metastases and choroidal melanomas: comparison of ultrasonographic
      findings.
AB  - AIMS: The purpose of the study was to analyse, whether the shape and the height
      to base ratio in B-scan ultrasonography are appropriate to differentiate
      choroidal melanomas from metastases. METHODS: Between 1991 and 1996 16 eyes of 16
      patients with choroidal metastases from breast carcinomas and 66 eyes of 66
      patients with choroidal melanomas were evaluated ultrasonographically. The
      diagnosis of choroidal melanoma has been confirmed histologically in all eyes.
      Irradiated tumours were excluded from the study. Fisher's exact test and chi 2
      test were used for statistical analysis. RESULTS: Choroidal metastases
      demonstrated a significantly lower height to base ratio in B-scan (mean 0.18, SD
      0.08) than melanomas (mean 0.6 (0.16); p < 0.001). A polygonal tumour surface was
      significantly more frequent in metastases (13 out of 16 metastases and in six out
      of 66 melanomas, p < 0.001). A choroidal excavation could be demonstrated in 38
      melanomas and in no metastatic tumour (p < 0.001). The reflectivity was
      significantly higher in metastases than in melanomas. CONCLUSION: The combined
      use of height to base ratio and reflectivity enables a highly significant
      discrimination between choroidal melanomas and metastases from the breast, thus
      probably constituting appropriate variables for the clinical differentiation.

PMID- 9613383
TI  - Effect of isovolaemic haemodilution on visual outcome in branch retinal vein
      occlusion.
AB  - AIMS: To assess the efficacy of isovolaemic haemodilution therapy (IHT) in the
      treatment of patients with branch retinal vein occlusion (BRVO). METHODS:
      Patients presenting with BRVO between 1 July 1991 and 31 August 1993 were
      eligible for inclusion and randomised into treatment and control groups. Patients
      randomised to receive IHT were treated for 6 weeks with venesection and volume
      replacement using hydroxyethylstarch, a plasma expander. The target haematocrit
      was 35%. Follow up was for 1 year. RESULTS: The baseline visual acuity of the two
      groups was similar at 0.74 and 0.75 logMAR units (Snellen 6/36), for the IHT and
      control groups, respectively. At 6 weeks, visual acuity in the IHT group had
      improved by 0.20 logMAR units (2 lines on the Bailey-Lovie chart) (p = 0.0001).
      Vision was unchanged in the control group. At 1 year, the IHT group exhibited an
      improvement of 0.43 logMAR units. By comparison, the improvement in the control
      group at 1 year was significantly less at 0.17 logMAR units (p = 0.03). The final
      visual acuity in the IHT and control groups was 0.30 (Snellen 6/12) and 0.60
      (Snellen 6/24) logMAR units, respectively. CONCLUSIONS: The results support the
      theory that IHT has a positive effect on the visual outcome in patients with
      BRVO.

PMID- 9613384
TI  - Objective measurement of contrast sensitivity function using contrast sweep
      visual evoked responses.
AB  - AIM/BACKGROUND: The contrast sensitivity function (CSF) measurement provides
      information that is not accessible by standard visual acuity determinations. The
      contrast sweep pattern reversal visual evoked responses (CSVER) technique was
      used to objectively measure the CSF in clinical practice. METHODS: The contrast
      thresholds were measured at five spatial frequencies in 10 normal subjects. The
      CSVER were recorded with sinusoidally modulated vertical gratings at 10 contrast
      levels (96, 64, 48, 32, 16, 8, 4, 2, 1, and 0.5%) presented in five spatial
      frequencies (0.5, 1.0, 2.0, 4.0, and 8.0 cycles per degree). Each of 10 contrast
      levels was displayed for 2 seconds at the desired spatial frequency. The CSVER
      amplitudes at the second harmonic were calculated by discrete Fourier transform.
      The results were compared with those obtained using a psychophysical method.
      RESULTS: An inverted U-shaped CSF which peaked at 2.0 cycles per degree with a
      contrast sensitivity of 34.5 (contrast, 2.9%) was observed. The CSF assessed
      electrophysiologically was 0.62 to 0.79 log units lower than the sensitivity
      measured using the psychophysical method. However, the overall shapes were highly
      correlated. CONCLUSION: One can objectively measure CSF with CSVER and this may
      be useful in patients in whom the psychophysical method is limited.

PMID- 9613385
TI  - Correction of lower eyelid retraction in thyroid eye disease: a randomised
      controlled trial of retractor tenotomy with adjuvant antimetabolite versus
      scleral graft.
AB  - BACKGROUND/AIMS: Lower eyelid retraction in thyroid eye disease contributes to
      ocular discomfort and an unsightly appearance, especially if asymmetrical. The
      use of donor scleral grafts is effective in lengthening the lower eyelids but
      carries a risk of virus transmission. Other techniques, including those which do
      not use grafts, need to be compared with scleral grafts. Recurrent retraction is
      a recognised complication of thyroid eyelid surgery; therefore, the authors
      investigated the use of antimetabolites to reduce postoperative fibrosis.
      METHODS: In this prospective randomised controlled trial of 25 patients (35
      eyelids), the use of donor sclera in 20 lower eyelids (13 patients) was compared
      with partial tenotomy of the anterior part of the lower eyelid retractors (ALER)
      with adjuvant peroperative antimetabolite in 15 lower eyelids (12 patients). A 5
      minute peroperative application of either 5-fluorouracil (25 mg/ml) in nine lower
      eyelids (eight patients) or mitomycin C (0.2 mg/ml) in six lower eyelids (four
      patients) was used to focally inhibit fibroblasts. Follow up ranged from 3 to 18
      months (mean 7.8). RESULTS: One month after surgery the results of both groups
      were similar. However, at 3 months after surgery the results of scleral grafting
      were better than tenotomy with antimetabolites: 3/12 patients (25%) treated with
      tenotomy and adjuvant antimetabolite required subsequent surgery using grafts for
      correction of recurrent retraction. There were no significant complications
      associated with the use of antimetabolites in the eyelid in the doses used in
      this study. CONCLUSIONS: This randomised prospective trial shows that donor
      scleral grafts were more effective in the long term than partial tenotomy with
      adjuvant antimetabolite in the correction of lower eyelid retraction associated
      with thyroid eye disease. The use of peroperative antimetabolites in the lower
      eyelid was safe.

PMID- 9613386
TI  - Platelet derived growth factor and fibroblast growth factor basic levels in the
      vitreous of patients with vitreoretinal disorders.
AB  - AIM: To determine the potential role of basic fibroblast growth factor (bFGF) and
      platelet derived growth factor (PDGF) in the pathogenesis of proliferative
      vitreoretinopathy (PVR). METHODS: An enzyme linked immunosorbent assay technique
      was used to determine the quantities of bFGF and PDGF in 38 vitreous samples
      taken from patients undergoing trans pars plana vitrectomy (PPV) for a variety of
      vitreoretinal disorders. RESULTS: bFGF levels ranged from undetectable to 318.7
      pg/ml. The mean concentration was 27.57 pg/ml. PDGF levels ranged from
      undetectable to 160 pg/ml, the mean concentration being 40.06 pg/ml. Eight of 13
      patients with clinical evidence of retinal detachment (RD) and PVR had
      significantly elevated bFGF concentrations, whereas only one of 11 patients with
      RD and no PVR had detectable bFGF; seven of eight patients with RD and PVR had
      elevated PDGF concentrations in the vitreous, whereas all 10 patients with RD and
      no PVR had no detectable vitreous PDGF. Eight patients with vitreous haemorrhage
      had raised PDGF concentrations, and the levels were particularly high (> 120
      pg/ml) in those two patients with active neovascularisation. Two out of nine
      patients with vitreous haemorrhage had raised bFGF levels. CONCLUSIONS: bFGF and
      PDGF concentrations are elevated in PVR even in the absence of vitreous
      haemorrhage, and not in patients with RD uncomplicated by PVR. This observation
      suggests that both cytokines may be involved in the pathogenesis of PVR.

PMID- 9613387
TI  - Effect of cigarette smoking on copper, lead, and cadmium accumulation in human
      lens.
AB  - AIM: To identify cigarette smoking as a risk factor for development of cataract,
      to determine the importance of copper, lead, and cadmium in cataractogenesis, and
      to learn about any relation between those elements. METHODS: Copper, lead, and
      cadmium concentrations were measured by atomic absorption spectrophotometry in 37
      cataractous and nine normal human lenses. RESULTS: All three element
      accumulations in lenses with cataract were statistically meaningful. Lenticular
      copper, lead, and cadmium were increased significantly with cigarette smoking.
      Cadmium had a positive correlation both with lead and copper in cataractous
      lenses. CONCLUSION: The accumulation of copper, lead, and cadmium occurs in
      cataract. The probable source of cadmium in humans is cigarettes. Lenticular
      cadmium accumulation also increases copper and lead precipitation in the lens.
      Cigarette smoking might be cataractogenic.

PMID- 9613389
TI  - Microcystic adnexal carcinoma masquerading as a chalazion.

PMID- 9613390
TI  - Optic disc dimensions, body length, and body weight.

PMID- 9613388
TI  - Albinism: modern molecular diagnosis.

PMID- 9613391
TI  - Orbital Wegener's granuloma resulting from direct extension of nasal disease
      through a surgical rhinostomy.

PMID- 9613392
TI  - Rhodococcus keratitis.

PMID- 9613393
TI  - Anterior ischaemic optic neuropathy in a child with AS haemoglobinopathy and
      migraine.

PMID- 9613394
TI  - Ocular trauma from party balloons.

PMID- 9613395
TI  - Osteoporosis: a survey of consultant ophthalmologists.

PMID- 9613396
TI  - Effect of PRK on intraocular pressure measurements and on keratometry.

PMID- 9613397
TI  - Deep lamellar keratoplasty with complete removal of pathological stroma for
      vision improvement.

PMID- 9613398
TI  - A report by the British Orthopaedic Association/British Association of Plastic
      Surgeons Working Party on the management of open tibial fractures. September
      1997.
AB  - We congratulate the authors of this excellent combined report. What a pleasure it
      is to find two surgical specialties cooperating in this way. The working party
      has carefully analysed the available data, considered the various options for
      management and proffered clear advice which we hope will be useful for all
      surgeons managing these difficult injuries. The message of collaboration was
      conveyed in the first edition of the report. This stressed that, in order to
      avoid repeated surgery and long term disability, it is necessary to evaluate each
      injury and to establish communication between the two disciplines as soon as
      possible, with the aim of providing optimal conditions for wound and fracture
      healing. The working party feels that this message now needs re-emphasising and
      it is our hope that this latest report, by up-dating and repeating the principles
      of management, will lead to a further improvement in outcomes.

PMID- 9613399
TI  - Naming of parts: a presentation of facial surface anatomical terms.

PMID- 9613400
TI  - Outcome analysis of a modified Tajima procedure.
AB  - Secondary nasal correction of cleft patients is acknowledged to be a difficult
      problem. There are many different operations but few objective assessments of
      their results. We have evaluated the results of a modified Tajima operation by
      use of the Bristol computer technique. Eighteen patients were followed up for a
      mean of 33 months (range 10-56). Measures of asymmetry were obtained for
      different photographic views, preoperatively and at later postoperative visits.
      In all views there was a significant improvement in shape in the early
      postoperative photos. This same improvement was also seen when comparing
      preoperative to late postoperative results i.e. this initial improvement is
      maintained over time. There was no significant difference between the early and
      late postoperative views. In this small series the modified Tajima technique has
      given statistically significant lasting improvement. However, few other
      operations have been objectively assessed and hence comparison is difficult. We
      advocate the use of the computer technique for other procedures to allow
      meaningful comparisons between them.

PMID- 9613401
TI  - Oral reconstruction using the peroneal flap.
AB  - Eight cases of oral reconstruction using the peroneal flap are reported. Six are
      for tongue and two are for oral wall. All flaps survived completely. The peroneal
      flap has many merits: the flap is thin and wide, the peroneal vessels have a
      large diameter lumen and long pedicle, the donor site has few sequela, and
      simultaneous surgery is possible. In addition, the characteristics of the flap
      skin change gradually to that of mucous membrane, and hairs disappear in a year
      or two. We believe that for reconstruction of the oral cavity the peroneal flap
      is a better source than any other flap.

PMID- 9613402
TI  - Malignant tumours of the parotid gland: a 12-year review.
AB  - Malignant parotid tumours are uncommon and present a significant management
      challenge. Fifty-one such patients (25 male, 26 female, median age 64 years)
      operated on in the Newcastle Plastic Surgery Unit between 1983 and 1994 were
      retrospectively evaluated. Preoperative investigations included FNA cytology (n =
      20), and for staging CT and/or MRI scans (n = 21). Of the 35 primary tumours 32
      were epithelial and three lymphomatous. Metastatic tumours were squamous cell
      carcinoma (7), melanoma (6), renal cell carcinoma (2) and sebaceous carcinoma
      (1). FNA cytology correctly diagnosed malignancy with an 88% sensitivity (false
      negatives = 2). A total or radical parotidectomy was required in 60% of patients,
      the rest undergoing superficial parotidectomy. In continuity neck dissection was
      undertaken in 23 (45%) cases. Postparotidectomy reconstruction included 10 free,
      3 myocutaneous, and 4 local transposition/rotation flaps. Thirty-seven patients
      (73%) received postoperative radiotherapy. Seventy-two per cent of patients are
      alive after a mean follow-up of 42 months. The crude 5- and 10-year survival
      rates were 68% and 49% respectively while the loco-regional control rate (Kaplan
      Meier method) at 10 years was 79%. Fifteen patients (30%) have permanent facial
      palsy. It is concluded that radical surgery with appropriate reconstruction
      followed by planned postoperative adjuvant radiotherapy gives effective control
      of malignant parotid tumours.

PMID- 9613403
TI  - The influence of the graft length on the functional and morphological result
      after nerve grafting: an experimental study in rabbits.
AB  - Clinical experience shows that the results after the use of long nerve grafts for
      reconstruction are sometimes poor. Nevertheless several authors have stressed
      that the concomitant big defect in the soft tissues necessitating the use of long
      grafts is the reason for some of the failures. In 22 rabbits the saphenous nerve
      was used as a nerve graft. Animals were separated into 3 groups with different
      lengths of the grafts, namely 3 cm (group 1), 5 cm (group 2) and 7 cm (group 3).
      In the left hindlimb the proximal end of the graft was coapted to the cut motor
      nerve branch of vastus medialis. In a second stage the distal end of the graft
      was coapted to the nerve branch of rectus femoris. After a total period of 15
      months the maximum tetanic tension in the reinnervated rectus femoris and in the
      contralateral unoperated muscle was determined. Biopsies of the graft and the
      motor branch distal to the graft were taken in order to count the number of
      regenerated myelinated nerve fibers. The average maximum tetanic tension in the
      rectus femoris muscle reinnervated by the 3 cm long graft was 27.2 N, in group 2
      the force was 20.5 N. In group 3 the maximum force was 17.6 N, which meant an
      average loss of 29% compared to the contralateral unoperated muscle. The mean
      number of regenerated myelinated fibres distal to the graft in the rectus femoris
      motor branch was 1683 in group 1 and decreased to 1137 in group 3. The results
      show that the length of the graft influences the results after nerve grafting to
      a certain extent, but a combination of other factors like concomitant soft tissue
      injury and destroyed target organs may also be responsible for some of the poor
      results after the clinical use of long nerve grafts.

PMID- 9613404
TI  - Immunosuppression following thermal injury: the pathogenesis of
      immunodysfunction.

PMID- 9613406
TI  - Silicone breast implants: complications.
AB  - Silicone breast implants have been used for augmentation mammoplasty for cosmetic
      purposes as well as for breast reconstruction following mastectomy for more than
      three decades. Though the use of the silicone gel filled variety has been banned
      in the USA except for special cases, they continue to be available elsewhere in
      the world including the UK. Despite the immense benefit they provide, their usage
      is associated with some complications. Most of these are related to the surgery
      and can be reduced by good surgical management. The major complications
      associated with their use is adverse capsular contracture, an outcome which can
      be very frustrating to manage. This article reviews the commonly reported
      complications and suggested management alternatives.

PMID- 9613405
TI  - The effect of felodipine on endothelin-1 levels, peripheral vasoconstriction and
      flap survival during microvascular breast reconstruction.
AB  - Endothelin-1 (ET-1) may contribute to vasoconstriction and flap blood flow during
      microvascular surgery. Calcium antagonists have suppressed ET-1 release in some
      studies. The effect of 5 mg of felodipine, a vasodilating calcium antagonist,
      administered the evening and morning before a microvascular TRAM (transverse
      rectus abdominis musculocutaneous) flap breast reconstruction, on perioperative
      plasma ET-1 concentrations, peripheral temperature gradient (Tgrad), rectal
      temperature (Trect), flap skin blood flow with transcutaneous oxygen tension
      (ptcO2), heart rate (HR) and mean arterial pressure (MAP) was evaluated in this
      clinical, randomised, double blind, prospective study. Felodipine did not cause
      any statistically significant changes in ET-1 levels, Tgrad, Trect, Ptc O2, flap
      survival or pre- or intraoperative MAP. HR was significantly higher in the
      felodipine group before induction and at 10 min postoperatively. We conclude that
      in patients undergoing a microvascular TRAM flap breast reconstruction,
      preoperatively administered felodipine has no effect on perioperative ET-1
      levels, temperature changes, or flap skin blood flow.

PMID- 9613407
TI  - Informed consent: are we doing enough?
AB  - We report our findings in a prospective, randomised study of patient recall of
      verbal versus written preoperative warnings. There were 132 patients in the
      verbal group and 137 in the written group, with a similar age and sex
      distribution in both groups. Four of the seven preoperative warnings were
      remembered significantly better by the group receiving the written warnings (P <
      0.001-0.05). However, the mean number of warnings recalled was fewer than 3 in
      the verbal group, and fewer than 4 (P = 0.0057) in the written group (Mann
      Whitney U-test). Patients given verbal warnings were less able to recall them
      than those receiving written warnings. The inference is that they entered into
      surgery less well informed.

PMID- 9613408
TI  - Bipedicle flaps: simple solutions for difficult problems in the extremities.
AB  - Bipedicle flaps have been used to provide good quality soft tissue cover for
      defects in many anatomical sites. The indications for the use of this flap have
      not been well defined and with the advent of more complex modes of tissue
      transfer this simple technique is often overlooked. We have found it to be a safe
      and expedient method of providing cover for difficult defects on the extremities.
      We present a series of 9 flaps raised on 7 patients over a 12-month period and
      discuss the indications and refinements in flap design.

PMID- 9613409
TI  - Facial palsy following trauma to the external ear: 3 case reports.
AB  - We report two children and a young adult who developed unilateral facial palsy
      shortly after injury to the external ear. In two instances the paralysis followed
      a prominent ear correction and in the other a laceration to the concha. The
      trauma-triggered facial palsy was most likely idiopathic although the anatomy of
      the facial nerve near the ear leads one to speculate on a possible pathway of a
      virally induced palsy (Bell's palsy). Each patient recovered over a period of 6
      months.

PMID- 9613410
TI  - Congenital lower lip sinuses in Nigerian children.
AB  - Two patients with congenital lower lip sinuses are presented. This condition is
      extremely rare and has not previously been reported in the black populations of
      Africa. The embryology, clinical features and the literature are reviewed.

PMID- 9613411
TI  - Step-wise lengthening for delayed repair of avulsion of the flexor pollicis
      longus.
AB  - Repair of late avulsion of the flexor pollicis longus tendon at insertion is a
      rare but difficult problem. A 52-year-old female labourer presented with a 3
      month history of inability to flex her right thumb at the interphalangeal joint.
      Avulsion of the flexor pollicis longus tendon at its insertion was noted on
      exploration. Because the tendon had contracted and could not be reinserted
      directly, a technique of step-wise lengthening was used for reinsertion. Two
      months after operation, the patient resumed her daily activities and went back to
      work with satisfactory use of her right thumb. This report highlights the
      possibility of using a simple technique when there is no other alternative.

PMID- 9613412
TI  - Anomalous flexor digitorum superficialis muscle belly: an unusual case of mass in
      the palm.
AB  - A case of anomalous superficialis muscle belly in the palm is presented. Nineteen
      such cases have been reported until now. Our case differs in that the anomalous
      muscle originated from the flexor digitorum superficialis tendon to the index
      finger by way of an accessory tendon.

PMID- 9613413
TI  - Stepladder V-Y advancement flap for repair of postero-plantar heel ulcers.
AB  - Random fasciocutaneous flaps with bilateral adipofascial pedicles were elevated
      from the posterior heel and transferred distally to defects of the postero
      plantar heel in 4 patients, using a stepped incision technique, in combination
      with the V-Y advancement principle. In all cases the flap was successfully
      transferred without any linear scar or scar contracture in the posterior heel.
      The absence of recurrence of ulcers during the postoperative follow-up between
      1.5 and 4 years indicated the reliability and durability of the flaps.
      Application of this procedure permits rapid resurfacing and excellent
      recontouring of small to moderate-sized defects of the heel with minimal donor
      site morbidity.

PMID- 9613414
TI  - David Napier Matthews 1911-1997.

PMID- 9613415
TI  - Inflammatory reaction to subcuticular Vicryl suture following tuberculin test.

PMID- 9613416
TI  - Tax allowances for surgical telescopes.

PMID- 9613417
TI  - The distally-based islanded dorsal foot flap.

PMID- 9613418
TI  - Video microsurgery: additional experience.

PMID- 9613419
TI  - The cutaneous innervation of the female breast and nipple-areola complex:
      implications for surgery.

PMID- 9613420
TI  - Regional perfusion and oxygenation in the pedicled latissimus dorsi muscle flap.

PMID- 9613421
TI  - Venous enhancement of a distally-based islanded fasciocutaneous flap.

PMID- 9613422
TI  - The distally-based islanded dorsal foot flap.

PMID- 9613423
TI  - Sleep apnoea in endocrine diseases.
AB  - The pertinent literature on the prevalence, clinical manifestations and
      pathogenic mechanisms of sleep apnoea (SA) in endocrine diseases, namely
      acromegaly, Cushing syndrome, hypothyroidism and diabetes mellitus was reviewed.
      An increased prevalence is well documented in patients with active and treated
      acromegaly. While most authors report peripheral obstruction, due to hypertrophy
      of tongue and pharyngeal tissues, to be the cause of SA in acromegaly, some
      findings argue for a role of hormone-induced changes of central respiratory
      control. SA is also more common in hypothyroidism, especially when myxedema is
      present. The associated edema and myopathy appear to be of pathogenic importance.
      Thyroxin substitution is frequently effective for the treatment of SA but nCPAP
      can be necessary initially and in some patients even after remission of clinical
      signs of hypothyroidism. In Cushing disease and syndrome, parapharyngeal fat
      accumulation can cause SA, but no epidemiological information is available. In
      non insulin dependent diabetes (NIDDM), obesity is the common risk factor for
      both, nocturnal hypoxia and insulin resistance. In IDDM, the development of
      autonomic neuropathy may predispose to SA. Where treatment of the underlying
      endocrine disease is unable cure the associated SA, nCPAP is usually the
      treatment of first choice. More prospective studies are clearly needed to
      establish prevalences and resolve the controversies regarding pathogenesis.

PMID- 9613424
TI  - Story-like organization of dream experience in different periods of REM sleep.
AB  - Four dream reports, collected from each of 16 subjects in an experimental night,
      were analysed using the criteria of Mandler and Johnson's story grammar. The
      experimental night was the first of the four nights where subjects had
      spontaneously given a dream report after each of the four awakenings planned in
      REM sleep. A multivariate analysis of covariance, taking the order of the nights
      where the experimental night occurred and the order of reports as factors, the
      number of stories per report as covariate and the number of statements in the
      setting, the number of statements in the event structure and number of episodes
      per story as dependent variables, showed that the greater length and complexity
      of reports collected in the second half of the night depends on a greater
      effectiveness of the dream production system rather than on a greater accuracy of
      recall. This increase concerns the organization of individual stories rather than
      the number of stories developed in a given time. These findings raise the issue
      of how dream production is re-triggered during REM sleep. To cast light on this
      issue, it seems important to establish whether and how the themes of the various
      stories developed in a given dream experience are interrelated.

PMID- 9613425
TI  - The siesta culture concept is not supported by the sleep habits of urban Mexican
      students.
AB  - Evidence in support for the concept of the so-called 'siesta culture' is not well
      developed and has, to date, relied largely on qualitative anthropological data.
      Presumably such cultures are characterized by a strong tendency for daytime naps
      and daytime sleepiness, phenomena which may partially represent the effects of
      geographic, climatic or light conditions and/or cultural influences. In this
      study we surveyed the nocturnal sleep habits and daytime sleep tendencies of 577
      Mexican college students residing in Mexico City (19 degrees N latitude). Results
      indicated a number of parallels between the reported sleep habits of these
      students and those reported from other cultures at latitudes far to the north
      (North America, Europe), such as longer sleep at the weekends, an association
      between snoring and daytime sleepiness and a lack of relationship between
      nocturnal sleep duration and the reported tendency to nap. There was some
      suggestion that these Mexican students may actually nap less when compared to
      other college student populations. Taken together, these results call into
      question what is meant by the concept of a 'siesta culture', at least in this
      urban, educated, upper social economic scale (SES) population, and suggest that
      future studies in equatorial regions be undertaken to further appreciate the role
      of climate, photoperiod and/or culture in the tendency for humans to nap during
      the day.

PMID- 9613426
TI  - Effects of medium- and long-chain triglycerides on sleep and thermoregulatory
      processes in neonates.
AB  - Sleep processes and body temperature regulation of neonates are never taken into
      account in the evaluation of nutrients, although these functions are implicated
      in the regulation of energy metabolism and are influenced by the nutritional
      state and its metabolic consequences. Medium-chain triglycerides (MCT) are
      currently used in paediatric units during the first weeks of because they are
      considered to be a rapid source of energy, easy to assimilate for growing
      premature infants, whose digestive function is immature. However, no study has
      described the thermic effect of these nutrients on body temperature regulation
      and sleep. The present study aimed at analysing the influence of three feeding
      formulas with different content of MCT on sleep processes and on thermoregulation
      of neonates fed until desired intake was reached. Whatever the thermal conditions
      (thermal equilibrium or cool environment), the MCT-fed groups had higher body
      temperatures and than groups fed without MCT, for whom total sleep time was
      reduced at thermal equilibrium. In this group, the large amount of quiet sleep
      seems to favour a strategy of conserving energy. Higher energy expenditure in MCT
      fed groups is not harmful to growth rate since nutritional efficiency is even
      better reflected by a larger body mass gain. The thermic effect of MCT
      contributes to lessening the vulnerability of neonates exposed to low incubator
      temperatures.

PMID- 9613427
TI  - The clinical diagnosis of the narcoleptic syndrome.
AB  - Sleep-wake habits and control of postural muscle tone were investigated by self
      report questionnaire in 183 subjects considered to have the narcoleptic syndrome,
      62 subjects with hypersomnia and 10 with obstructive sleep apnoea. Results were
      compared with those in a group of 188 control subjects with normal sleep wake
      habits. Excessive daytime sleepiness, determined by the Epworth Sleepiness Scale
      (ESS), was five times greater in the narcoleptic syndrome than in control
      subjects (score range 0-24, mean scores +/-SD 19.6+/-3.0; and 4.5+/-3.3
      respectively; P<0.001). The propensity to cataplexy, as determined by a rating
      scale developed to estimate the likelihood of loss of postural tone in response
      to sudden emotional stimuli, including laughter, was 10 times greater in
      narcoleptic syndrome than in control subjects (postural atonia total score range
      0-600; mean + SD 334+/-122 and 28+/-45, respectively; P<0.001). Narcoleptics had
      more disturbances of night sleep than controls with episodes of muscle jerking,
      sleep walking, sleep talking and sleep terrors, as well as sleep paralysis, and
      higher insomnia self-rating scores. Sleep latency from bedtime to sleep-onset
      time was shorter in narcoleptics than controls. The hypersomniac group of 62
      subjects was heterogeneous. Subsequent investigation showed that 18 subjects
      (29%) had idiopathic hypersomnia, four (6%) 'incomplete' narcolepsy without
      cataplexy and 10 (16%) hypersomnia accompanying a mood disorder. The mean ESS
      scores in this group and in subjects with obstructive sleep apnoea were
      comparable to those of the narcoleptic syndrome subject group. Mean postural
      atonia scores were similar to those of control subjects.

PMID- 9613428
TI  - Autonomic markers of arousal during sleep in patients undergoing investigation
      for obstructive sleep apnoea, their relationship to EEG arousals, respiratory
      events and subjective sleepiness.
AB  - Estimating the degree of sleep fragmentation is an important part of a
      respiratory sleep study and is conventionally measured using EEG micro arousals
      or is inferred indirectly from respiratory abnormalities such as apnoeas and
      desaturations. There is a need for less labour-intensive measures of sleep
      fragmentation, and transient rises in blood pressure and heart rate may fulfil
      this role. Forty unselected sleep clinic referrals undergoing investigation for
      possible obstructive sleep apnoea (OSA) were studied with one night of
      polysomnography. Three conventional indices of sleep fragmentation (EEG micro
      arousals, apnoea/hypopnoea index (AHI) and oxygen saturation dip rate (SaO2
      dips)) and two autonomic indices (heart rate and blood pressure rises) have been
      compared. Correlations between these five indices ranged from r=0.38 to r=0.73.
      Of the two autonomic indices, the correlations for blood pressure rises with SaO2
      dips and EEG micro arousals were stronger (r=0.71 and r=0.65, respectively) than
      those for heart rate rises (0.55 and 0.51). All indices of sleep fragmentation,
      apart from heart rate rises, were similar in their correlation with subjective
      sleepiness (r-values 0.21-0.36). Arousals implied from blood pressure rises
      (using pulse transit time) can be measured easily, are objective, and appear no
      worse at predicting subjective sleepiness than either EEG micro arousals or AHI.
      They may therefore provide a useful alternative to manual scoring of micro
      arousals from the EEG as an index of sleep fragmentation in sleep clinic patients
      undergoing investigation for possible OSA.

PMID- 9613430
TI  - Does post-torpor EEG slow wave activity in ground squirrels reflect a 'sleep
      debt' or a thermoregulatory process?

PMID- 9613429
TI  - Sleep bruxism based on self-report in a nationwide twin cohort.
AB  - The relative roles of genetic and environmental factors in bruxism are not known.
      In 1990 a questionnaire sent to the Finnish Twin Cohort yielded responses from
      1298 monozygotic and 2419 dizygotic twin pairs aged 33-60 years. We used
      structural equation modelling to estimate genetic and environmental components of
      variance in the liability to bruxism. There was a significant gender difference
      both in childhood (P = 0.001) and adult (P = 0.007) bruxism. Females compared to
      males reported childhood bruxism 'often' 5.2% vs 4.1% and 'sometimes' 17.4% vs
      17.3%, and as adults 'weekly' 3.7% vs 3.8% and 'monthly' 3.9% vs 4.6%,
      respectively. Bruxism in childhood and adulthood is highly correlated (0.86 in
      males and 0.87 in females). The proportion of total phenotypic variance in
      liability to bruxism attributed to genetic influences in childhood bruxism was
      49% (95% CI 37-60%) in males and 64% (55-71%) in females, and for adults 39% (27
      50%) among males and 53% (44-62%) among females. The correlation between the
      genetic effects on childhood bruxism and the genetic effects on adult bruxism was
      estimated in a bivariate model to be 0.95 (95% CI 0.94-0.96) in males and 0.89
      (0.88-0.90) in females. Bruxism appears to be quite a persistent trait. There are
      substantial genetic effects on bruxism both in childhood and as adults, which
      appear to be highly correlated.

PMID- 9613431
TI  - Autoantibody profiles in canine ANA-positive sera investigated by immunoblot and
      ELISA.
AB  - Canine systemic lupus erythematosus (SLE) has a similar disease expression as
      human SLE, but the serological characterisation of the canine disease is as yet
      incomplete. In the present study, we examined the specificity of antinuclear
      antibodies (ANA) in indirect immunofluorescence (IIF) positive canine sera. Sixty
      four canine IIF ANA positive sera were characterised using HeLa cell nuclear
      extract immunoblots and recombinant U1-70K ELISA. We compared these results with
      a previously shown concordance between indirect immunofluorescence and
      immunodiffusion in canine SLE serological diagnosis. One canine serum reacting
      with Sm proteins was observed, and five canine sera presented anti-RNP
      autoantibodies against the antigens 70K, A, C, and/or B/B'. The autoantigen most
      frequently recognised was a 43 kDa nuclear protein, previously described as hnRNP
      G. This prominent canine autoantigen was missing in the commercially available
      extract designed for immunodiffusion testing of human sera. Other prominent
      canine autoantigens were found not to be identical with the principal human ones,
      thus making present human test systems deficient for the use in canine systemic
      connective disease diagnosis. The development of antigenic extract designed for
      canine autoimmune autoantigens is necessary in order to make immunodiffusion a
      useful method in canine diagnosis. The anti-RNP positive canine sera were
      examined in more detail and we found that the human major antigenic region of the
      most prominent RNP antigen, the U1-70K protein, also is targeted by canine
      autoantibodies. Thus, the response against the RNP antigen seems to be conserved
      between man and dog.

PMID- 9613432
TI  - Expression of major histocompatibility complex class II antigens in the canine
      intestine.
AB  - Immunohistochemical techniques were used to assess major histocompatibility
      complex (MHC) class II expression by enterocytes and lamina propria cells in the
      canine intestinal tract. Duodenal enterocyte class II expression was faint and
      limited to the lower crypt region whereas jejunal and ileal enterocyte expression
      was stronger, being present in both crypt and villus areas. Enterocyte staining
      was of greatest intensity in crypts adjacent to Peyer's patches and intense
      membrane staining of most Peyer's patch lymphocytes was also seen. Enterocyte MHC
      class II expression in the colon was largely limited to the lower crypt region.
      Within the lamina propria, of all intestinal sites examined, a heterogeneous
      population of cells were MHC class II positive and these had morphological
      features of macrophages and dendritic cells. Lymphocytes, plasma cells,
      fibroblasts and vascular endothelium were not stained. Definition of constitutive
      expression of MHC class II within the canine intestine may be important in
      identifying upregulation of this molecule in inflammatory bowel diseases.

PMID- 9613433
TI  - Expression of adhesion and Fcgamma-receptors on canine blood eosinophils and
      neutrophils studied by anti-human monoclonal antibodies.
AB  - Commercially available anti-human monoclonal antibodies were tested as markers of
      adhesion receptors and Fcgamma-receptors on canine neutrophils and eosinophils.
      Purified populations of eosinophils and neutrophils were incubated with selected
      monoclonal antibodies and binding was measured by flow cytometry. Most of the
      anti-human monoclonal antibodies used in this study crossreacted with canine
      granulocytes and many showed expression similar to that of human granulocytes.
      The results suggest that the adhesion and Fcgamma-receptors are well conserved
      among species. Canine eosinophils and neutrophils were simultaneously purified by
      a two-layer Percoll density gradient centrifugation. The purity of the neutrophil
      fraction was > or = 97% after lysis of the erythrocytes. In the eosinophil
      fraction, 27-92% were eosinophils (mean 60%). After purification, the neutrophils
      and eosinophils were incubated with selected monoclonal antibodies and analysed
      by flow cytometry. Human anti-CD11b and CD18 antibodies bound intensely to both
      canine eosinophils and neutrophils. Canine neutrophils did label with anti-CD29,
      but eosinophils did not. Anti-CD49d bound weakly to both eosinophils and
      neutrophils. Both anti-CD16 and anti-CD32antibodies labelled neutrophils, but not
      eosinophils. There was no binding of anti-CD9 to canine neutrophils and the
      binding of anti-CD9 to canine eosinophils varied between dogs.

PMID- 9613434
TI  - Development of monkey C-reactive protein (CRP) assay methods.
AB  - Monkey-specific C-reactive protein (CRP) assay methods (enzyme-linked
      immunosorbent assay (ELISA) and turbidimetric immunoassay (TIA)) were developed.
      The anti-monkey CRP serum was prepared by immunization of rabbits with the immune
      complex formed between the acute-phase serum from turpentine oil-inoculated
      monkeys and goat anti-human CRP serum. The specificity of the rabbit anti-monkey
      CRP serum was confirmed by immunoelectrophoresis and Western blotting. The purity
      of monkey CRP prepared by chromatography procedures was confirmed by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The serum CRP
      levels in nine normal monkeys, as measured by sandwich ELISA were ranged from
      0.26 to 1.42 microg/ml (mean 0.71+/-0.37). The CRP levels in five acute-phase
      sera of turpentine oil-inoculated monkeys were 248-451 microg/ml (mean 371.2+/
      73.8). This monkey-specific CRP assay method was found more sensitive than the
      human-specific CRP assay method in detecting monkey CRP by TIA.

PMID- 9613435
TI  - Spontaneous Borna disease in sheep and horses: immunophenotyping of inflammatory
      cells and detection of MHC-I and MHC-II antigen expression in Borna encephalitis
      lesions.
AB  - Borna disease (BD) has been recognized as a virally induced T-cell dependent
      immunopathological disorder of the central nervous system (CNS), as shown by
      experimental infection of rats with Borna disease virus (BDV). In contrast to the
      rat model, little is known about the pathogenesis of spontaneous BD in sheep and
      horses. The present study describes the brain lesions of 12 ovine and 11 equine
      cases of naturally occurring BD. A set of monoclonal and polyclonal antibodies
      was used in order to determine the cells operative in encephalitic lesions and to
      detect expression of MHC-I and MHC-II products in the brains of affected animals.
      In all cases investigated, a reaction pattern similar to that reported for the
      acute phase of BD in experimentally infected rats was noted. In brief, the
      majority of inflammatory cells in perivascular infiltrates (PVI) as well as
      parenchymal and meningeal infiltrates were CD3 +. CD4 + cells outnumbered CD8 +
      cells in PVI as well as in the parenchyma. Macrophages (defined by lysozyme
      immunoreactivity) were seen less often and B-cells or plasma cells (cells
      positive for lambda or kappa light chains) were demonstrated at lower numbers.
      TCR-1 + cells were found on very rare occasions in PVI of some sheep. MHC-I and
      MHC-II products were constantly expressed on inflammatory cells but
      inconsistently on astrocytes and neurons. Neuronal degeneration was not a major
      feature.

PMID- 9613436
TI  - Ovine cutaneous squamous cell carcinoma: immunohistochemical expression of CD3,
      CD4, CD8 and MHC class II antigens in the associated inflammatory infiltrate.
AB  - The immunohistochemical expression of CD3, CD4, CD8 and MHC class II antigens in
      the cellular inflammatory infiltrate associated with early and advanced ovine
      squamous cell carcinomas (OSCC), as well as actinic keratosis was analyzed. The
      majority of the peritumoral and intratumoral lymphocytes reacted with the anti
      human CD3 polyclonal antibody. The number of CD8+ T lymphocytes increased in
      advanced OSCC compared with that of actinic keratosis and early OSCC, whereas the
      number of CD4+ lymphocytes was similar in early and advanced OSCC. Tumor cells
      were unreactive with the anti-MHC class II antibody, but the majority of the
      mononuclear cellular infiltrate expressed this antigen in early and advanced
      tumors.

PMID- 9613437
TI  - Lack of a specific immune response against a recombinant capsid protein of
      Jaagsiekte sheep retrovirus in sheep and goats naturally affected by enzootic
      nasal tumour or sheep pulmonary adenomatosis.
AB  - Enzootic nasal tumour (ENT) and sheep pulmonary adenomatosis (SPA) are two
      contagious adenocarcinomas of the respiratory tract of sheep and goats. Both
      diseases are associated with related, but distinct, type-D-retroviruses (ENTV and
      JSRV respectively). No evidence of circulating antibodies has been described in
      animals affected by either ENT or SPA using antigens from natural sources. We
      evaluated the usefulness of a recombinant JSRV capsid protein (JSRV-CA) as
      antigen to study the antibody responses of animals naturally affected by ENT or
      SPA, using immunoblotting. Positive reactions were detected in the sera of both
      affected and unaffected sheep and goats. The reactivity was abolished completely
      by absorption with the GST fusion partner but not by JSRV-CA, suggesting that it
      was not specific. The results support prior observations indicating that sheep
      and goats infected by JSRV and ENTV do not develop specific humoral responses to
      these retroviruses.

PMID- 9613438
TI  - Testing of bovine sera by ELISA for IgG, IgM and IgA rheumatoid factors.
AB  - Sera from 19 colostrum-deprived calves less than 1 week old, 24 colostrum
      supplemented calves less than 1 week old, 36 3-5-month-old calves and 200 females
      greater than 9 months of age were tested by ELISA for the presence of IgM, IgG
      and IgA rheumatoid factors (RF). An increasing level of IgM- and IgG-RF with age
      was found. IgG-RF levels in the colostrum-supplemented calves were significantly
      higher than in the non-supplemented calves (p < 0.001). Individual IgG-RF values
      correlated with serum IgG levels, as determined by zinc sulphate turbidity
      testing (r=0.59, p < 0.01). No IgA-RF was detected. The cross-reactivity of IgM
      RF with heterologous IgG was found to be greatest with rabbit IgG, followed by
      mouse and chicken IgG. The significance of rheumatoid factors in relation to
      diagnostic testing is discussed.

PMID- 9613439
TI  - Kinetics of expression and subset distribution of the TNF superfamily members
      CD40 ligand and Fas ligand on T lymphocytes in cattle.
AB  - CD40 and Fas are members of the tumor necrosis factor receptor (TNFR)
      superfamily. CD40 and Fas play key roles in T cell-B cell interactions. Cross
      linkage of these molecules induces cell activation and cell death, respectively.
      The interaction of CD40 with its ligand (CD40L), which is expressed on activated
      T cells, plays a pivotal role in the generation of the T-dependent (TD) immune
      response, and FasL-bearing T cells, which have been shown to be predominantly of
      either the TH0 or TH1 type, have the potential to induce the apoptotic death of
      Fas expressing B cells. We investigated bovine CD40L mRNA expression in
      established T cell clones by RT-PCR and Southern blotting. T cells analyzed
      included CD4+ TH0 and TH1 cell subpopulations, CD8+, and gamma/delta T cells
      stimulated with either specific antigen or Con A. All CD4+ clones but not all
      CD8+ or gamma/delta T cell receptor (TCR)-bearing clones expressed mRNA for
      CD40L. To determine the activation requirements for CD40L expression in cattle,
      we examined the kinetics and induction requirements for CD40L transcription in
      peripheral blood T cells using a phorbol ester and/or ionomycin, immobilized
      mouse anti-bovine CD3, or Con A. Our results demonstrate that CD40L mRNA appears
      relatively early after activation (1 h) and peaks at 2-4 h poststimulation. A
      rise in intracellular calcium concentration mediated by ionomycin treatment alone
      was sufficient to induce CD40L mRNA expression at relatively high levels.
      Ionomycin treatment in combination with other agonists (anti-CD3, PMA) did not
      enhance CD40L mRNA expression above levels obtained with ionomycin alone. The
      bovine Fas ligand gene was partially cloned and mRNA expression determined by RT
      PCR in a panel of T cell clones. Our results demonstrate that TH0 and TH1 bovine
      T cell clones expressed Fas ligand transcripts although only one gamma/delta T
      cell clone did. This expression was upregulated within 3 h after mitogen
      stimulation and reduced by 24 h.

PMID- 9613440
TI  - Quantitative detection of porcine interferon-gamma in response to mitogen,
      superantigen and recall viral antigen.
AB  - Five monoclonal antibodies (mAbs) specific for porcine interferon-gamma (PoIFN
      gamma) were isolated and utilized to develop a PoIFN-gamma sandwich ELISA.
      Specific reactivity of each mAb with E. coli derived recombinant PoIFN-gamma, but
      not with rPoIL-2 or rPolL-10, was confirmed in an indirect ELISA and in Western
      blots. Competitive ELISAs showed that mAbs P2A4 and P2C11 bound an epitope which
      was not recognized by mAbs P2G10, P1B7 or P2F6. The latter three mAbs were able
      to neutralize the ability of natural and recombinant PoIFN-gamma to induce the de
      novo expression of class II MHC antigens on porcine endothelial cells. To
      simplify the detection of biologically active porcine IFN-gamma, a sandwich ELISA
      was developed using the mAb P2G10 as a capture antibody and mAb P2C11 as the
      detecting reagent. The sensitivity of the assay for PolFN-gamma ranged from 1 to
      50 ng/ml. Peripheral blood mononuclear cells (PBMC) from all pigs tested produced
      IFN-gamma when stimulated with either mitogen (PHA) or superantigen (SEB). In
      contrast, only PBMC obtained from pigs which had previously been vaccinated
      against PrV produced IFN-gamma in response to stimulation with this virus.
      Interestingly, cultures with the highest lymphoproliferative response did not
      necessarily have the highest level of IFN-gamma production.Furthermore, for
      recall viral antigen, the lymphoproliferative response decreased with time after
      immunization, whereas the IFN-gamma response increased. Thus, measurement of IFN
      gamma production appears to be a good indicator of anti-viral immunological
      memory.

PMID- 9613441
TI  - Inducible nitric oxide synthase expression in porcine immune cells.
AB  - Porcine immune cells were examined for the ability to produce inducible nitric
      oxide synthase following in vitro or in vivo stimulation. Enzyme activity and
      product formation were not detected following stimulation of porcine peripheral
      blood mononuclear cells (PBMC), splenocytes, or alveolar macrophages with a
      combination of ConA and lipopolysaccharide (LPS) or recombinant porcine
      interferon gamma and LPS. In vitro engulfment of Haemophilus parasuis by
      macrophages also failed to induce inducible nitric oxide synthase (iNOS) activity
      or nitrite formation. Swine Herpes Virus infection led to a small but significant
      increase in level of nitrite detected in lung lavage fluid, whereas the infection
      of pigs with Porcine Respiratory and Reproductive Syndrome Virus did not alter
      the lavage fluid nitrite levels. iNOS mRNA was detected in both stimulated and
      unstimulated porcine immune cells and in macrophages from both control and
      infected animals suggesting that it is constitutively expressed with little or no
      upregulation following cellular stimulation. The results presented in this paper
      indicate that the reactive nitrogen intermediate pathway is not an vital innate
      immune response in the pig.

PMID- 9613442
TI  - Immune responses and side effects of five different oil-based adjuvants in mice.
AB  - In this study, five different oil based adjuvants were compared to assess
      efficacy and side effects. Mice were injected subcutaneously (s.c.) or
      intraperitoneally (i.p.) with a weak immunogen (synthetic peptide) emulsified in
      Freund's adjuvant (FA), Specol, RIBI, TiterMax or Montanide ISA50. Efficacy of
      adjuvants was evaluated based on their properties to induce peptide specific
      IgG1, IgG2a and total IgG antibodies, native protein cross-reactive antibodies
      and cytokine production. Side effects were evaluated based on clinical and
      behavioural abnormalities, and (histo)pathological changes. Although marked
      differences in isotype profile and height of titre are observed among the
      different adjuvants used, we found that FA, Montanide ISA50 and Specol worked
      equally well in the s.c. and i.p. route, TiterMax functioned only when given i.p.
      and RIBI also did not perform up to par. The number of cytokine (interferon-gamma
      and interleukin-4) producing spleen cells was significantly higher after
      injection of RIBI compared with other adjuvants. Injection of FA or TiterMax
      resulted in severe pathological changes while after RIBI injection minimal
      changes were observed. In conclusion, high peptide specific antibody levels with
      limited side effects can be obtained by s.c. injection of peptide combined with
      Montanide ISA50 or Specol as alternatives to FA.

PMID- 9613443
TI  - Oral and parenteral vaccination of mice with protein-ergotamine conjugates and
      evaluation of protection against fescue toxicosis.
AB  - Acremonium coenophialum produces ergopeptide alkaloids in tall fescue (Festuca
      arundinacea Schreb.). These ergot alkaloids decrease serum alkaline phosphatase
      (ALP) activity, serum cholesterol and prolactin concentrations, as well as
      average daily gains (ADG) in cattle. The objective of this study was to evaluate
      the protection of anti-ergotamine antibodies induced by either oral or parenteral
      vaccination with protein-ergotamine conjugates or passive vaccination with anti
      ergovaline, monoclonal antibodies in a murine model of fescue toxicosis.
      Ergotamine (EG) was conjugated to bovine serum albumin (BSA) and cholera toxin
      subunit B (CTB) by the Mannich reaction. Mice were blocked based on weight and
      randomly allocated into five groups of 10 mice each. Treatment groups were as
      follows: (1) group vaccinated intraperitoneally (ip) with a BSA-EG conjugate and
      fed an endophyte-infected (EI) fescue diet (BSA-EG group); (2) group orally
      vaccinated with a CTB-EG conjugate mixed with free cholera toxin (CT) and fed an
      EI fescue diet (CTB-EG group); (3) nonvaccinated group fed an EI fescue diet (EI
      group); (4) group passively vaccinated with anti-ergovaline, monoclonal
      antibodies and fed an EI fescue diet (MoAB group); and (5) nonvaccinated group
      fed an endophyte-free (EF) fescue diet (EF group). The EI diet contained 1.5 ppm
      of Ergovaline (EV), whereas no EV was detected in the EF diet.Respective diets
      were similar upon nutritional analysis. Unvaccinated mice in the EI group
      exhibited features of fescue toxicosis as indicated by decreased serum ALP
      activity and cholesterol, and decreased weight gain as compared to mice in the EF
      group. Antibodies against EG and EV were present in sera of mice in the BSA-EG
      and MoAB groups, respectively. Mice orally vaccinated with the CTB-EG conjugate
      developed secretory IgA (sIgA) antibodies and short-lived, systemic IgG responses
      against EG. Weight gains were increased in the BSA-EG and CTB-EG groups and
      tended to be increased in the MoAB group vs. the unvaccinated EI group. Serum ALP
      activity was decreased in the BSA-EG and MoAB groups as compared to the EF group.
      Serum ALP activity was further decreased in the BSA-EG vaccinated group as
      compared to the EI group. Cholesterol concentrations were decreased in the EI,
      BSA-EG and MoAB groups as compared to the EF group. Prolactin concentrations were
      similar in all groups.

PMID- 9613444
TI  - The expression and regulation of inducible nitric oxide synthase gene differ in
      macrophages from chickens of different genetic background.
AB  - It has been previously reported that lipopolysaccharide (LPS)-stimulated
      macrophages from Cornell K-Strain chickens (B15B15) and a transformed cell line,
      MQ-NCSU, (broiler origin) produced significantly higher levels of inducible
      nitric oxide synthase (iNOS) mRNA than macrophages isolated from GBI (B13B13) and
      GB2 (B6B6) chickens. The purpose of this study was to determine the basis of such
      differential iNOS gene expression and to study the relationship of high or low
      expression of iNOS mRNA with iNOS enzyme activity in macrophages from GB2 (low
      iNOS mRNA expresser), K-strain and MQ-NCSU (high iNOS mRNA expressers). The
      enzyme activity in lysates from LPS-stimulated macrophages was lower in GB2
      (range: 23 to 41 microM, P < 0.05) as compared with the K-strain and MQ-NCSU
      macrophages that exhibited intermediate (range: 27 to 59 microM) and the highest
      (range: 144 to 217 microM) activity, respectively. Total RNA collected from LPS
      treated macrophages at various time-points post-actinomycin D treatment revealed
      comparable iNOS mRNA levels in MQ-NCSU, GB2, and K-strain macrophages, suggesting
      that post-transcriptional regulation mechanism(s) do not account for the
      difference in iNOS mRNA expression. To determine if differences in the
      transcription rate are the basis of the differential iNOS gene expression,
      macrophages were stimulated with or without LPS and nuclei-isolated. Inducible
      NOS mRNA probes were generated and hybridized with immobilized iNOS cDNA (reverse
      Northern blot). The resulting lumigraph yielded enhanced transcriptional activity
      from K-strain and MQ-NCSU macrophages whereas this activity was lower in GB2
      macrophages. Therefore, these studies suggest that the previously reported
      genetically-based difference in iNOS mRNA expression further translates into
      differences in iNOS enzyme activity, and that the iNOS gene in chickens is
      transcriptionally regulated.

PMID- 9613445
TI  - Enhanced expression of cytokine genes in spleen macrophages during acute
      infection with infectious bursal disease virus in chickens.
AB  - We examined the effects of infectious bursal disease virus (IBDV) on splenic T
      cells and macrophages. In acute IBDV infection, splenocytes responded poorly to
      Con A stimulation. However, when T cells were isolated from whole spleen cells,
      purified T cells responded normally to Con A. This result indicated that
      functional T cells were present in the spleen but mitogen-induced proliferation
      of T cells was being suppressed by other cells. Previous studies indicated that
      soluble factors from suppressor cells may mediate this inhibition of T cell
      mitogenesis. We thus examined the effects of IBDV on spleen adherent cells.
      Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to quantitate
      the expression of several cytokine genes in splenic macrophages. In acute IBDV
      infection, splenic macrophages exhibited enhanced gene expression of type I
      interferon (IFN), chicken myelomonocytic growth factor (cMGF), an avian homolog
      of mammalian IL-6, and 9E3/CEF4, an avian homolog of mammalian IL-8. Mitogen
      stimulated spleen cell cultures also produced elevated levels of nitric oxide.
      The elevation of cytokine gene expression by macrophages occurred transiently
      during the acute phase of viral infection and coincided with in vitro inhibition
      of T cell mitogenic response of spleen cells.

PMID- 9613446
TI  - Characterisation of chicken monocytes, macrophages and interdigitating cells by
      the monoclonal antibody KUL01.
AB  - The distribution, function and ontogeny of the mononuclear phagocyte system of
      the chicken were characterised using the monoclonal antibody (MAb) KUL01. KUL01
      specifically recognises chicken monocytes, macrophages and interdigitating cells,
      as well as activated microglia cells. Its tissue distribution allowed to
      discriminate KUL01 from all earlier described MAb, reactive with mononuclear
      phagocytes. The specificity of KUL01 for mononuclear phagocytes was further
      confirmed in functional assays: KUL01-positive macrophages in spleen and liver
      actively took up colloidal carbon, while monocytes and spleen and gut macrophages
      contained non-specific esterase and acid phosphatase activities characteristic
      for antigen-processing. Further, it was demonstrated that KUL01-reactive
      peripheral blood monocytes express MHC-II, but not CD4. In all tissues
      investigated, the same morphological subtypes of macrophages were detected in
      chicken at similar localisations as in mammals, indicating a high degree of
      conservation between the mononuclear phagocyte system of the chicken and of
      mammals.

PMID- 9613447
TI  - Neurotrophins and their receptors in the pigeon caecal tonsil. An
      immunohistochemical study.
AB  - Neurotrophins are growth factors which bind to signal-transducing receptors
      called Trk proteins. The neurotrophins and their receptor proteins are present in
      the mammalian and avian lymphoid organs, thus suggesting that these factors could
      act upon cells of the immune system. Nevertheless, little is known about the
      cellular distribution of neurotrophins and their receptor proteins in avian
      lymphoid tissues. In this study we use immunohistochemistry to detect the
      cellular localisation of neurotrophins and their receptor proteins in the pigeon
      caecal tonsil, used as a model for avian secondary lymphoid organs. Rabbit
      polyclonal antibodies against neurotrophins (nerve growth factor -NGF-, brain
      derived neurotrophic factor -BDNF- and neurotrophin -3 NT-3-) and against
      specific epitopes of TrkA, TrkB and TrkC proteins were used. Cytokeratins,
      vimentin, S-100 protein and chromogranin A were studied in parallel to identify
      cells which seemed to express neurotrophins and Trk proteins. TrkA-like protein
      was seen in the intestinal epithelium, whereas TrkB-like and TrkC-like proteins
      was found in cells which we identified as dendritic cells and macrophages. BDNF
      like and NT-3-like reactivity was localised in intestinal epithelial cells,
      especially endocrine cells. Present results add further evidence to the
      presumptive immune role of neurotrophins and their receptors and the possible
      functions of these peptides in the caecal tonsil are discussed.

PMID- 9613448
TI  - Immunostimulatory effects of dimerized lysozyme (KLP-602) on the nonspecific
      defense mechanisms and protection against furunculosis in salmonids.
AB  - Utilization of natural immunostimulants in fish culture offers a wide range of
      attractive methods for inducing and building protection against diseases.
      Lysozyme is an enzyme with bacteriolytic properties and is ubiquitous in its
      distribution among living organisms. This enzyme has antiviral, antibacterial and
      anti-inflammatory properties. In nature, lysozyme is found as a monomer. Lysozyme
      dimer is significantly less toxic than its monomer, and its high biological
      activity has been ascertained in cases of both viral and bacterial infections. In
      our study, we examined the influence of dimerized lysozyme (KLP-602) on the
      nonspecific cellular and humoral defense mechanisms and protection against
      furunculosis in rainbow trout (Oncorhynchus mykiss). We have analyzed the
      immunomodulatory effects of KLP-602 after experimental infection by Aeromonas
      salmonicida. Application of dimerized lysozyme (KLP-602) by injection stimulated
      the cellular and humoral defense mechanisms and provided protection against
      furunculosis. By contrast, mortality rate was reduced to 45% (one injection) and
      25% (three injections) using 10 or 100 microg/kg KLP-602. Mortality in the
      untreated control group was 85%.

PMID- 9613449
TI  - Cloning and sequencing of cDNA encoding bovine tumor necrosis factor (TNF)
      receptor I.
AB  - Tumor necrosis factor (TNF) is a multipotent cytokine produced by activated
      macrophages and lymphocytes and its activity is mediated by specific cell surface
      receptors, TNF-RI and TNF-RII. We have isolated and analyzed a cDNA encoding
      bovine TNF-RI gene and compared it with known TNF-RI sequences from other
      species. The cDNA sequence for the coding region of bovine TNF-RI shows 80%
      homology with porcine TNF-RI and 77% with human TNF-RI. The cDNA sequence of
      bovine TNF-RI codes for 471 amino acids and shows 75% and 67% identity with the
      amino acid sequences of porcine TNF-RI and human TNF-RI, respectively. The
      predicted bovine TNF-RI amino acid sequence consists of a signal peptide, an
      extracellular domain, a transmembrane region and a cytoplasmic tail. The
      extracellular region contains four repeated cysteine rich domains, which are
      conserved in all species. Northern blot results show that bovine TNF-RI gene is
      expressed in neutrophils and mononuclear leukocytes.

PMID- 9613450
TI  - Stimulation of macrophage phagocytosis and lymphocyte count by exogenous
      prolactin administration in silver sea bream (Sparus sarba) adapted to hyper- and
      hypo-osmotic salinities.
AB  - Juvenile silver sea bream (Sparus sarba) were adapted to hyper- (33 ppt) and hypo
      osmotic (6 ppt) salinities for 3 weeks and injected daily with ovine prolactin (1
      microg/g body weight i.p.) during the last 7 days of the adaptation period. Fish
      injected with prolactin exhibited significant increases in percent phagocytosis
      and phagocytic index of both pronephric and splenic macrophages regardless of
      salinity. Prolactin injection also resulted in elevated blood lymphocyte counts
      in both hyper- and hypo-osmotically adapted sea bream. The present results
      provide further evidence for the existence of a neuroendocrine-immune link in
      teleosts.

PMID- 9613451
TI  - Environmental and occupational aspects on the etiology of non-Hodgkin's lymphoma.
AB  - Immunosuppression, possibly in combination with viruses, could be a main
      etiologic mechanism for non-Hodgkin's lymphoma (NHL). Chemicals such as
      phenoxyacetic acids, chlorophenols, dioxins, organic solvents, polychlorinated
      biphenyls, chlordane, and immunosuppressive drugs have been associated with this
      disease. Also UV light and blood transfusion have been postulated to be risk
      factors. Conclusive evidence of a causal association with NHL is not established
      for all of these exposures, but experimental evidence and clinical observations
      indicate that all these exposures have in common that they may impair the immune
      system. Furthermore, acquired and congenital immune deficiency as well as
      autoimmune disorders increase the risk for NHL. In view of currently available
      evidence, the first priority for reducing morbidity due to NHL might be to take
      action against adverse chemical exposures as a measure that is more easily
      achievable than any other kind of prevention.

PMID- 9613452
TI  - Effect of retinoic acid on morphological changes of human pancreatic cancer cells
      on collagen gels: a possible association with the metastatic potentials.
AB  - Pancreatic carcinoma is an invasive and metastasizing type of malignancy. We
      established six pancreatic cancer cell lines from human pancreatic carcinomas,
      three highly metastatic lines (KP-1NL, KP-4, and SUIT-2) and three minimally
      metastatic lines (KP-2, KP-3, and BxPC-3). The three highly metastatic cell lines
      grew in a fibroblastoid pattern on collagen gels, whereas the three minimally
      metastatic cell lines grew in an epithelioid pattern under similar conditions.
      Western blot and Northern blot analyses indicated much higher levels of E
      cadherin in the three minimally metastatic cell lines relative to the three
      highly metastatic cell lines. When the effect of all-trans-retinoic acid on the
      growth patterns of the three highly metastatic lines was examined, we observed a
      dramatic change from fibroblastoid to epithelioid growth in SUIT-2 cells.
      Although all six cell lines had comparable levels of retinoic acid receptor
      gamma, retinoic acid receptor-beta was expressed only in SUIT-2 cells. Treating
      SUIT-2 cells with retinoic acid also induced the upregulation of E-cadherin
      expression. When SUIT-2 cells were treated with retinoic acid receptor-specific
      agonists, 13-cis-retinoic acid and Am555S, a morphological change from
      fibroblastoid to epithelioid growth was induced. Retinoic acid receptor-specific
      antagonists, LE135 and LE540, inhibited retinoic acid-induced change of the
      growth patterns. The effect of retinoic acid and its derivatives on the growth
      pattern was discussed in a possible association with their antimetastatic
      activities of pancreatic cancer.

PMID- 9613453
TI  - Antiangiogenesis and apoptosis as mediators of concomitant tumor resistance
      induced by Calu-6, a human lung carcinoma cell line, in nude mice.
AB  - Concomitant resistance (CR), the phenomenon by which tumor-bearing hosts are able
      to inhibit secondary implants of the same tumor at distant sites of the body, has
      been previously observed by us and others in different murine tumor models. Here,
      we verified the generation of CR in nude mice by tumors induced by SC inoculation
      of Calu-6, a human lung carcinoma cell line. Histological analysis of secondary
      tumors subject to CR did not reveal macrophage infiltration nor cytotoxic signs.
      Although serum from tumor-bearing mice inhibited in vitro [3H]thymidine uptake by
      Calu-6 cells, no significant differences in [3H]thymidine labeling index of
      tumors implanted in the right flank of mice with and without a primary tumor in
      the left flank were detected. In our model, the presence of a primary tumor
      hindered remote tumor angiogenesis, as well as serum from tumor-bearing mice
      inhibited in vitro proliferation of an endothelial cell line derived from a
      murine hemangioendothelioma. Conversely, an enhancement of the apoptotic index
      was observed in secondary tumor implants carried out in tumor-bearing mice. The
      results reported herein show that human tumor cells are capable of inducing CR,
      and that this phenomenon would be a consequence of an impaired neovascularization
      as well as an increased programmed cell death at sites distant from the primary
      tumor.

PMID- 9613456
TI  - Vitamin D receptor gene polymorphism is associated with metastatic breast cancer.
AB  - The vitamin D receptor (VDR) has been detected in breast tumor cells. We tested
      the hypothesis that VDR gene polymorphism might influence the outcome of women
      affected by breast cancer. A total of 88 breast cancer patients were recruited:
      50 women were affected by newly diagnosed breast cancer whereas 38 women suffered
      from relapsing disease. The individual genetic pattern for VDR was evaluated by
      DNA extraction followed by PCR amplification of the VDR gene, and digestion with
      the restriction enzyme BsmI. In 167 healthy women, participating in the
      osteoporosis prevention trial and being used as a control, we detected 121 Bb
      heterozygotes (72%), 26 homozygotes for the bb alleles (16%), and 20 homozygotes
      for the BB alleles (12%). In the newly diagnosed breast cancer group the
      occurrence of Bb patients was 58% (29/50); bb patients represented 22% (11/50),
      and BB cases were 20% (10/50). The VDR frequency distribution in the control and
      primary disease patient groups was not statistically different. In the metastatic
      cancer group, the prevalence of the bb genotype (14/38; 37%) was double the
      percentage of control subjects, whereas the percentage of BB women with
      metastases was half the control group (2/38; 5%). Women who were homozygous bb
      appeared to have almost a four times higher risk of developing metastases than BB
      women. Whatever the molecular mechanisms underlying the VDR effects in cancer
      cells, we believe that the VDR gene polymorphism may represent an important
      determinant in the evaluation of women affected by breast cancer and might help
      design targeted therapy.

PMID- 9613454
TI  - Assessment of protein conformation in human benign and malignant astrocytomas by
      reflectance Fourier transform infrared microspectroscopy.
AB  - The secondary structure and composition of protein in the tissues of benign and
      malignant astrocytomas were determined by reflectance Fourier-transform infrared
      (FT-IR) microspectroscopy. The peak maximum of IR spectra of the tissues from
      recurrent malignant astrocytoma markedly appeared at higher frequency (1655 or
      1663 cm(-1)), which was significantly different from that of the tissues from
      benign astrocytoma at 1651 cm(-1) and tissues from malignant astrocytoma at 1652
      cm(-1). Malignant astrocytoma indicated slightly different compositions in the
      protein secondary structure from benign astrocytoma. However, a significant
      increase in beta-turn structure but a marked decrease in beta-sheet and random
      coil structures were observed in the protein secondary structure of the recurrent
      malignant astrocytoma. The phenomenon was more pronounced in recurrent malignant
      astrocytoma pretreated with radiation and chemotherapy. The rapid cell
      proliferation and cell differentiation of malignant astrocytoma with or without
      recurrence might be the possible explanations for the different compositions of
      protein conformational structures.

PMID- 9613455
TI  - Characterization of 2-chloro-N10-substituted phenoxazines for reversing multidrug
      resistance in cancer cells.
AB  - Twenty-one 2-chloro-N10-substituted phenoxazines have been synthesized and
      characterized as potential modulators of multidrug resistance (MDR). Many of the
      compounds, at a concentration of 100 microM, enhanced accumulation of vinblastine
      (VLB) in drug-resistant KB8-5 cells to a greater extent than the same
      concentration of verapamil (VRP). However, the effects on VLB accumulation were
      specific, because these derivatives had little activity in the parental drug
      sensitive line KB3-1. The compounds slowed the efflux of VLB from KB8-5 cells,
      suggesting that the chlorophenoxazines, like VRP, can inhibit P-glycoprotein (P
      gp)-mediated efflux of VLB from this cell line. Two of the chlorophenoxazine
      derivatives, and also VRP, were able to stimulate the vanadate-sensitive ATPase
      activity attributable to P-gp in membranes isolated from MDR1 baculovirus
      infected Sf9 cells. This result suggests that these modulators exert their effect
      by directly interacting with P-gp. Apart from the parent unsubstituted molecule,
      2-chlorophenoxazine, there was a good correlation between log10P and the ability
      of the compounds to enhance VLB accumulation in KB8-5. This suggests that
      lipophilicity of a modulator is important, but is not the sole determinant of
      potency. Within this series of compounds, the optimal structural features for MDR
      modulation include a hydrophobic phenoxazine ring with a -Cl atom in the C-2
      position and a tertiary amine group four carbons from the tricyclic ring. Many of
      the agents at the IC10 concentration completely reversed the 37-fold VLB
      resistance in KB8-5 cells. The most active agents in KB8-5 were able to partially
      reverse VLB resistance in an MDR colon carcinoma cell line GC3/c1 and completely
      reversed the 86-fold VLB resistance in the MDR1-overexpressing breast carcinoma
      cell line BC19/3. These same agents could only partially sensitize BC19/3 cells
      to taxol and doxorubicin, suggesting that the chlorophenoxazine derivatives show
      some specificity for modulating VLB resistance.

PMID- 9613457
TI  - Correlates of urokinase-type plasminogen activator in colorectal cancer: positive
      relationship with nm23 and c-erbB-2 protein expression.
AB  - We undertook a study to analyze the expression of urokinase-type plasminogen
      activator (u-PA) protein in colorectal cancer (CRC) and to compare it with c-erbB
      2 (HER2/neu) and nm23 protein expression. Paraffin-embedded specimens from 58
      patients with CRC were retrospectively collected. Immunohistochemical staining of
      u-PA, c-erbB-2, and nm23 was quantitatively evaluated using a color video image
      analysis (color VIA) technique. No correlation was found between u-PA expression
      and tumor stage, age, sex, or tumor site. Although there was no evidence from our
      data that the level of u-PA in the primary tumors could predict risk of liver
      metastasis or survival duration, CRC showing overexpression of u-PA (above 85
      pixels) had a worse prognosis (P = 0.013). There were significant positive
      correlations among all three u-PA, c-erbB-2, and nm23 proteins (u-PA vs. c-erbB
      2, P = 0.003; u-PA vs. nm23, P < 0.001; c-erbB-2 vs. nm23, P = 0.001), suggesting
      that, in vivo, all proteins interact or are similarly regulated.

PMID- 9613458
TI  - Academic training for general practice.

PMID- 9613459
TI  - The London Academic Training Scheme: learning research methods through teaching.
AB  - BACKGROUND: The London Academic Training Scheme (LATS) provides a 1-year training
      programme in research methods and teaching for GPs who have recently finished
      vocational training. This paper describes an adult educational approach to
      learning about research methods through teaching as part of the LATS trainees'
      weekly academic programme. OBJECTIVE: We aimed to provide and evaluate a course
      exploring research methodologies used in primary care by a three-step approach to
      learning, with trainees taking the main role as teachers. METHOD: Trainees on the
      LATS programme met for one afternoon each week for one term. During alternate
      sessions a pair of trainees would deliver a whole afternoon's seminar on one
      aspect of primary care research methodology. The teaching of each session was
      evaluated by the whole group, by academic supervisors and by experts. RESULTS:
      Sessions were scored by participants for content, style of presentation,
      educational value and enjoyment on a seven-point rating scale where 1 = no value,
      4 = neutral and 7 = very valuable. All sessions scored above 4 and usually above
      5 for each aspect. Open comments collected showed that trainees greatly
      appreciated this self-directed approach to learning and teaching. CONCLUSION: The
      active involvement of learners as teachers is a practical and rewarding means of
      using adult educational principles in providing an academic programme.

PMID- 9613460
TI  - Aspirin after myocardial infarction: the importance of over-the-counter use.
AB  - BACKGROUND: Regular aspirin is beneficial after myocardial infarction (MI).
      Community-based surveys appear to show unsatisfactory uptake of aspirin after MI.
      This could be due to over-the-counter (OTC) use not being recorded. In a pilot
      study in one practice, 39% of patients on aspirin after MI used OTC preparations.
      In addition, women and older patients were less likely to use aspirin.
      OBJECTIVES: We aimed to describe aspirin use following MI in general practices in
      West London, including regimens and OTC use, and to demonstrate any association
      between aspirin use and gender, age or social class. METHODS: We used a postal
      questionnaire survey. The setting was a random sample of six general practices in
      Ealing, Hammersmith and Hounslow Health Authority who use Egton Medical
      Information Systems (EMIS) to store morbidity data. The subjects were registered
      patients with a history of MI. The main outcome measures were questionnaire data
      on aspirin use, regimen, OTC use, prescription charge exemption, age, gender,
      ethnic group and social class. RESULTS: The prevalence of previously recorded MI
      in all age groups was 0.64%. The response rate was 89%. Regular aspirin was used
      by 80%. Of these, 22% use OTC aspirin. OTC use was significantly more common in
      those paying prescription charges. Aspirin use was not associated with gender,
      age or social class. CONCLUSION: This study demonstrated a high uptake of aspirin
      among patients with previous MI as recorded by computer. OTC aspirin use was
      significant, and should be inquired about and recorded.

PMID- 9613461
TI  - Contraceptive knowledge and practice of pregnant teenagers requesting termination
      of pregnancy in inner-city London.

PMID- 9613463
TI  - Vitiligo: an under-estimated problem.
AB  - BACKGROUND AND OBJECTIVES: Vitiligo is a common skin complaint, affecting
      approximately 500000 people in the UK with cosmetically and psychologically
      devastating effects. An average GP will have 10 sufferers on his list. The aims
      of this survey were to determine the effects and extent of vitiligo, treatments
      used and whether these differed from those reported in the current medical
      literature. There has been no previous work in this area. METHOD: A self
      administered questionnaire was distributed to 25% of the members of the Vitiligo
      Society (a patients' self-help group) who were likely to be concerned about their
      condition. The questionnaire covered demographic characteristics of the group,
      the vitiligo itself, treatment and sufferers attitudes towards vitiligo. RESULTS:
      The response rate was 77%: the median age of onset was 13 years. Half related the
      onset of their vitiligo to a stressful event (e.g. marital and financial
      problems). Only 14% had noticed any spontaneous improvement in their vitiligo
      [negatively related to the percentage of vitiligo on the body (P < 0.05)]; 80%
      had used no treatment. Use of camouflage was high (41% of males and 70% of
      females). Sunscreen use was suboptimal, and 20% were depressed about their
      vitiligo. DISCUSSION: In this self-help group it appears that improvement occurs
      less frequently with more extensive vitiligo, so treatment (for vitiligo and
      depression) should be offered early. Further work on this subject is needed. GPs
      should be ideally placed to help vitiligo sufferers. The suboptimal use of
      therapies suggests that GPs need education about the topic.

PMID- 9613462
TI  - Do GPs prescribe antidepressants differently for South Asian patients?
AB  - BACKGROUND: In spite of evidence from controlled trials and published guidelines,
      general practitioners prescribe antidepressants in lower doses and for shorter
      courses than are recommended [2]. However, these studies have not examined the
      effect of ethnicity on antidepressant prescribing by general practitioners.
      OBJECTIVES: To compare the antidepressant treatment of South Asian patients with
      White patients. METHODS: Patients, between 16 and 65 years prescribed an
      antidepressant between November 1993-1995, were selected from an east London
      training practice by searching the practice computer system EMIS. From a total of
      438 patients identified, 40 cases were selected on the basis of their surname [3]
      as South Asian, and 50 cases formed the White comparison group. Data was
      collected retrospectively from the computer and paper records and analysed using
      Stata. The main outcome measures were presenting symptoms, maximum dose of
      antidepressant prescribed, duration of treatment and continuity of care. RESULTS:
      Women formed 2/3 of each group, the mean age in both groups being similar.
      Psychological symptoms were noted in the majority of both groups, but South
      Asians presented more physical complaints than the White group (67.5% compared to
      22%, Chi squared=18.86, P=0.00001). The South Asian group were significantly more
      likely to be prescribed amitriptyline at doses of 75 mg or less than the White
      group (Fisher exact 2 tailed test, P=0.008), had significantly shorter median
      durations of antidepressant treatment (60 days, compared with 160 days for the
      White group, Mann Whitney test P=0.005). No differences were found between the
      groups in their continuity of care. CONCLUSION: The results suggest that
      successful drug treatment of depressed South Asian patients may be less likely
      than in White patients.

PMID- 9613464
TI  - Assessing the likely effectiveness of screening older people for impaired vision
      in primary care.
AB  - Screening for visual impairment is frequently included in multiphasic screening
      assessments for older people, although evidence for the effectiveness of
      screening from randomized trials is lacking. This paper uses previously developed
      criteria for assessing the likely effectiveness of community screening programmes
      to review the non-trial evidence around visual screening. Unreported or
      undiagnosed visual impairment is common among older people and is associated with
      considerable morbidity. Testing for visual acuity is easy and quick, but may not
      accurately reflect the level of functional disability caused by the visual
      problem in everyday living. Effective therapeutic interventions exist for most
      symptomatic patients, but the effects of treating unreported visual impairment
      detected by screening have not been evaluated. Existing barriers to effective
      treatment for older people with symptomatic visual problems include financial
      costs to the patient, and an inability of ophthalmic services to meet demand.
      These same factors may be barriers to the uptake of treatment following
      screening. Further work is needed to assess the needs of older people with
      unreported visual problems, and to clarify barriers to effective screening.

PMID- 9613465
TI  - Why do patients call out-of-hours following a recent consultation with their GP?
      A qualitative study in one general practice.
AB  - BACKGROUND: The reasons for the increase in demand for out-of-hours primary care
      are not clear. OBJECTIVES: We aimed to elicit the proportion of patients who call
      out-of-hours within 2 days of a GP consultation, and to explore the reasons for
      the out-of-hours call. METHOD: In one inner-city general practice, details were
      collected of all out-of-hours calls, over a 6-week period. Patients who called
      out-of-hours within 2 days of a GP consultation were identified and interviewed.
      Twenty semi-structured interviews were analysed using standard qualitative
      techniques. RESULTS: Fifteen per cent of the out-of-hours calls occurred within 2
      days of a GP consultation. The reasons for the calls recorded by the doctor out
      of-hours and described by the patient at interview were similar. In two-thirds of
      cases the calls were related to the initial problem, but there was no evidence
      suggesting dissatisfaction with the first contact as a reason for the call. Less
      than a quarter of calls were for ongoing acute medical problems, and a quarter
      were about medication prescribed at the first consultation. A third of the
      patients had mental health problems with other physical, social and emotional
      problems. Many of this group were high users of this and other health services,
      including accident and emergency and private medicine. Some people called with
      specific queries or were seeking general information to enhance their
      understanding of illness. CONCLUSION: This small study in one inner-city practice
      indicates that patients do not appear to call out-of-hours due to dissatisfaction
      with a previous consultation. There seems to be a wide variety of reasons why
      this pattern of service use occurs. The diversity of patients and problems and
      the prevalence of people with multiple problems highlights current challenges in
      inner-city primary health care.

PMID- 9613466
TI  - What do doctors want? Altruism and satisfaction in general practice.
AB  - OBJECTIVE: Our aim was to consider the limitations of attempts to explain
      doctors' motivation in terms of altruism. METHODS: Doctors' consulting behaviour
      was considered as a performance which must be interpreted in relation to the
      diverse types of audience for whom it is intended. The concept of patient
      centredness was evaluated in the light of this discussion. Other possible sources
      of satisfaction were explored, including connection with, and disconnection from
      patients. CONCLUSION: It is suggested that satisfaction may be determined less by
      the achievement of specific outcomes than by the experience of complex
      interpersonal processes.

PMID- 9613467
TI  - The London Academic Training Scheme (LATS): an evaluation.
AB  - BACKGROUND: A recognition of the inability of vocational training schemes (VTS)
      to teach all the skills needed for modern general practice, and the increasing
      unwillingness of vocationally trained doctors to commit to GP principal posts,
      has led to the promotion and piloting of post-VTS educational schemes. The London
      Academic Training Scheme (LATS) is a year's attachment to a University Department
      of General Practice in London, comprising seven academic and three clinical
      sessions. OBJECTIVE: We aimed to carry out an evaluation of the first 2 years of
      the LATS from the perspectives of the registrar, their departmental supervisor
      and the practice. METHODS: Data were collected by questionnaires, interviews and
      focus groups, at the beginning, during and at the end of the scheme. RESULTS:
      Results are available up to the midway point of the second (1996) intake. The
      registrars achieved confidence and success in research, with six publications in
      peer-referenced journals from the first cohort so far. Eight of this cohort were
      working in inner London 6 months later, seven in academic posts. The overwhelming
      career intention of the second cohort midway is to work in academic general
      practice in London. The registrars enjoyed their teaching opportunities and
      increased their confidence but would have liked more training and more time for
      teaching. All the supervisors identified positive effects on their departments,
      but some found the time commitment and the process of supervision challenging.
      Two out of the dozen practices involved with the first cohort had reservations
      about the attachment. The rest cited benefits in clinical care, involvement in
      research and time for their own development. CONCLUSION: The scheme fulfilled its
      immediate aims and is addressing the recruitment and retention of GPs in the
      inner city. Continuing follow-up is planned.

PMID- 9613468
TI  - Studies on canine bone marrow long-term culture: effect of stem cell factor.
AB  - Long-term culture of canine marrow cells allows in vitro studies of the
      hematopoietic system of the dog and characterization of early progenitor cells.
      Colonies of fresh marrow cells grew equally good in both agar or methylcellulose
      supplemented with fetal calf serum, while colonies of long-term cultures required
      agar-based medium containing human serum. Optimum colony growth was obtained when
      stem cell factor (SCF) and granulocyte-macrophage-colony-stimulating factor (GM
      CSF) were used as growth stimuli of colony forming units (CFU). Similar results
      were achieved with several cell culture media. Addition of hydrocortisone to long
      term cultures improved clonogenic growth of cultured cells. Addition of 2
      mercaptoethanol had no effect. Strong differences were observed in long-term
      culture with different horse serum lots and the addition of fetal calf serum to
      long-term culture suppressed CFU growth of cultured cells. Recharging of cultures
      with fresh marrow cells on day 7 of culture improved CFU growth only in the
      following week but had little effect on the outcome. Adding SCF to long-term
      cultures led to differentiation of more primitive cells and destruction of the
      stromal layer. Investigation of purified and cultured cell populations was
      possible when preestablished long-term cultures as stromal layers were used. Loss
      of long-term culture-initiating ability could be demonstrated in this system with
      lineage negative marrow cells expanded ex vivo with SCF and GM-CSF.

PMID- 9613469
TI  - Characterization of anti-feline CD8 monoclonal antibodies.
AB  - We generated three monoclonal antibodies (mAbs) (2D7, 10C7 and 12A3) reactive to
      the alpha-chain of feline CD8 (fCD8) molecule. Further we showed that reference
      anti-fCD8 mAbs, FT2, 3.357 and vpg9 recognize the beta-chain, alpha-chain and
      alphabeta-complex epitope, respectively. Flow cytometric analysis using these
      mAbs suggested that fCD8alpha(+)beta(-) cells were present in lymphocytes of
      spleen, but not significantly in those of thymus, lymph nodes and peripheral
      blood of normal kittens.

PMID- 9613470
TI  - Characterisation of a monoclonal antibody recognising the CD3epsilon chain of the
      bovine T cell receptor complex.
AB  - We describe the characterisation of a monoclonal antibody (mAb), designated MM1A,
      which reacts with an antigen molecule on the surface of bovine alphabeta and
      gammadeltaTcR+ T cells. The mAb immunoprecipitated a series of polypeptides of 21
      kDa, 22 kDa, 32 kDa, 36 kDa and 44 kDa which is consistent with it recognising
      the TcR/CD3 complex. COS cells, transfected with a cDNA encoding the bovine
      CD3epsilon chain, reacted with mAb MM1A indicating that the epitope recognised is
      on the epsilon chain of the complex and confirming that the mAb recognised bovine
      CD3.

PMID- 9613471
TI  - Inhibition of MHC class I and class II cell surface expression on bovine
      endothelial cells upon infection with Cowdria ruminantium.
AB  - Endothelial cells constitute a main target for Cowdria ruminantium (CR) and can
      potentially play a role as antigen presenting cells (APC). Therefore, we
      measured, in vitro, the effect of CR infections on the expression of MHC class I
      and class II molecules on bovine umbilical endothelial cells (BUEC) and on bovine
      brain endothelial cells (BBEC). A dramatic inhibition of the expression of
      IFNgamma induced MHC class II molecules was observed on BUEC and to a lesser
      extent on BBEC upon CR infection. This inhibitory effect was also observed on
      constitutively expressed MHC class I molecules. Part of the reduction of cell
      surface MHC molecules could be ascribed to their accumulation in intracellular
      compartments pinpointing a disruption in the transit of these molecules to the
      surface of the cells. The exact mechanisms of inhibition are not yet known but,
      as opposed to what is described in other models, the involvement of prostaglandin
      E2 can be excluded. The results obtained in this study show that endothelial
      cells have a decreased capacity to express both MHC class I and class II
      molecules on their surface upon CR infection, thus favouring the escape of this
      pathogen from the host immune system.

PMID- 9613472
TI  - Immune responses in pigs infected with porcine reproductive and respiratory
      syndrome virus (PRRSV).
AB  - In three successive experiments, the immune functions of pigs persistently
      infected with the porcine reproductive and respiratory syndrome virus (PRRSV)
      have been evaluated. Non-specific immune responses were analyzed over a period of
      12 weeks post-infection (PI). In addition, the capacity of PRRSV-infected pigs to
      develop an efficient immune response against pseudorabies virus (PRV)
      glycoproteins and to resist to a subsequent virulent challenge was investigated.
      Our results demonstrate that PRRSV produced minor effects on the immune system of
      pigs. The skin delayed type hypersensitivity (DTH) in response to
      phytohemagglutinine injection was slightly diminished one week after challenge,
      but was restored thereafter. However, three weeks after the infection, the total
      white blood cell count, and the number of CD2+, CD8+ and IgM+ cells were
      enhanced. The increase in numbers of CD8+ cells persisted for three consecutive
      weeks. Serum immunoglobulins in infected pigs also increased by week 3 PI and up
      to 8 weeks PI. These results show that PRRSV may have stimulating effects on the
      pig immune system during the phase of long-lasting infection. After immunization
      with PRV glycoproteins, the production of anti-PRV antibodies and skin DTH
      response against PRV glycoproteins were not affected. On the contrary, following
      a virulent PRV challenge, PRRSV-infected pigs developed a better secondary
      antibody response and their resistance to the infection was as effective as in
      control pigs. Taken together, our data do not support a systemic
      immunosuppressive effect of PRRSV, during the persistent phase of infection.
      Other mechanisms may therefore apply to explain the emergence of secondary
      infections in endemically infected herds.

PMID- 9613473
TI  - Isolation and characterisation of pig Peyer's patch dendritic cells.
AB  - We have isolated dendritic cells (DC) from Peyer's patches (PP) of pig small
      intestine by mechanical tissue disruption followed by fractionation of isolated
      cells on metrizamide gradients. Characterisation was carried out using the
      following criteria: morphology; lysosomal enzyme synthesis; expression of
      membrane antigens; and capacity for antigen presentation. Dendritic cells did not
      express acid phosphatase or beta-galactosidase, but were weakly positive for non
      specific esterase and ATPase. Dendritic cells did not express CD3, CD2, sIg, or
      an antigen specific for pig mononuclear phagocytes and granulocytes. They did,
      however, express MHC class II at very high levels. They were shown to be potent
      stimulators in an allogeneic mixed lymphocyte reaction.

PMID- 9613474
TI  - Mycoplasma hyorhinis infection of pigs selectively bred for high and low immune
      response.
AB  - Pigs have been selected for high (H) or low (L) combined antibody and cell
      mediated immune response to test the high immune response phenotype as a
      candidate for an indirect approach to improving health and productivity in
      livestock. Mycoplasma hyorhinis infection was induced in H and L pigs of the 4th
      generation of selection to test the hypothesis that immune response lines differ
      in response to infection. The major disease sign, arthritis, was more severe in
      the H pigs both clinically and at necropsy. M. hyorhinis was isolated at higher
      colony counts from synovial fluids of the H pigs. In contrast, pleuritis and
      peritonitis were less severe in pigs of the H than those of the L line.
      Pericarditis, although less in H than L pigs, did not differ significantly by
      line. Synovial fluid antibody to M. hyorhinis did not differ by line but H pigs
      produced serum antibody earlier and to a higher titre than did L pigs. Selection
      for H or L immune response therefore alters response to M. hyorhinis, however
      there is no indication of a consistent line-related health advantage.

PMID- 9613475
TI  - Changing attitudes to infection management in primary care: a controlled trial of
      active versus passive guideline implementation strategies.
AB  - BACKGROUND AND OBJECTIVES: When attempting to implement evidence-based medicine,
      such as through clinical guidelines, we often rely on passive educational
      tactics, for example didactic lectures and bulletins. These methods involve the
      recipient in relatively superficial processing of information, and any consequent
      attitude changes can be expected to be short-lived. However, active methods, such
      as practice-based discussion, should involve recipients in deep processing, with
      more enduring attitude changes. In this experiment, the aim was to assess the
      efficacy of an active strategy at promoting deep processing and its
      effectiveness, relative to a typical passive method, at changing attitudes
      between groups of GPs over 12 months across an English Health District. METHODS:
      All 191 GPs operating from 69 practices in the Wirral Health District of
      Northwest England were assigned, with minimization of known confounding
      variables, to three experimental groups: active, passive and control. The groups
      were shown to have similar learning styles. The objective of the study was to
      impart knowledge of best management of infections as captured in a series of
      locally developed clinical guidelines. The passive group GPs were given a copy of
      the guidelines and were invited to an hour-long lecture event. The GPs in the
      deep group were given a copy of the guidelines and were invited to engage in an
      hour-long discussion about the guideline content at their own premises. The
      control group received neither the guidelines nor any educational contact
      regarding them. Three months before and 12 months after the interventions, all
      GPs were sent a postal questionnaire on their preferred empirical antibiotic for
      10 common bacterial infections. The responses were compared in order to ascertain
      whether increased knowledge of best clinical practice was evident in each group.
      RESULTS: Seventy-five per cent (144/191) of GPs responded to the pre-intervention
      questionnaire, 62 % (119/191) post-intervention. Thirty-four per cent (22/64) of
      GPs in the passive group attended the lecture; 91% (60/66) of the active group
      engaged in discussion at meetings with the authors. A significantly higher
      proportion of the active group participants' speaking time, during a sample of
      four visits, was devoted to verbal indicators of active processing than the
      passive group lecture attenders (difference = 55%, Fisher's exact test P = 0.002,
      OR = 11.5, 95% CI 2.1-113.4). Inter-observer agreement on the classification of
      the verbal evidence was highly statistically significant for all classes
      (Pearson's product moment correlation, P < 0.0005, r = +0.893 to +0.999) except
      repetition (P > 0.05, r = +0.407). Median compliance of responses with the
      guidelines improved by 2.5% within the control group and 4% within the passive,
      but by 23% within the active. The difference between the changes in the active
      and control groups was highly statistically significant at 17.5% (Mann-Whitney
      test, P = 0.004, 95% CI 6-29%). However, for the 10 infections, the median
      difference between the changes in the passive and control groups was not
      significant at 3% (P = 0.75, 95% CI -8 to +12. The median difference between
      changes in the active and passive groups was significant at 17% (P = 0.015, 95%
      CI 7-24%) in favour of the active. DISCUSSION: An active educational strategy
      attracted more participation and was more effective at generating deep cognitive
      processing than a passive strategy. A large improvement, lasting for at least 12
      months, in attitude-compliance with guidelines on the optimal treatment of
      infections was imparted by the active processing method. A typical passive method
      was much less popular and had an insignificant impact on attitudes. The findings
      suggest that initiatives aiming to implement evidence-based guidelines must
      employ active educational strategies if enduring changes in attitude are to
      result.

PMID- 9613476
TI  - Use of guidelines in primary care--practitioners' perspectives.
AB  - BACKGROUND AND OBJECTIVES: Concern about the inadequate take-up of guidelines in
      general practice has concentrated on problems arising from the process of their
      development and implementation. However, these perspectives fail to take account
      of the needs, attitudes and problems of GPs themselves. In this study we aimed to
      identify barriers to the use of guidelines and opportunities for tackling them,
      from the point of view of the GP, so that future guideline development and policy
      could be more sensitive to the needs of GPs in the environment in which they
      work. METHOD: Twenty in-depth semi-structured interviews were audiotaped with GPs
      from within the Avon Health Authority area, representing GPs with different
      backgrounds and working environments. The transcribed data collected were
      analysed using a grounded theory approach. RESULTS: Utilization of guideline
      information is complex. GPs' appraisals of the value of guidelines interact with
      prior knowledge and beliefs, practicalities of existing information storage and
      retrieval systems, and individual working practices. Conditions where guidelines
      are most likely to be referred to may be those either very rarely or very
      commonly presenting in general practice. Key issues for the uptake of guidelines
      in the consultation are: general preference for certain formats of presentation;
      reputability and ownership; use of guidelines in shared decision-making; scope
      for computer-based systems; and GPs' attitudes to time pressures on information
      seeking in relation to tolerance of uncertainty. CONCLUSION: Local initiatives
      might usefully explore the possibilities of supporting development of guideline
      retrieval systems customized for individual GPs or practices. Novel means of
      stimulating 'ownership' and demonstrating reputability should be sought. The
      analysis provides a framework for understanding the complexities of the processes
      of GPs' use of guidelines in practice which can be useful in explaining the
      results of trials of guideline effectiveness. Guideline implementation occurs in
      the context of conflicting pressures for clinical autonomy and professional
      standardization and quality improvement.

PMID- 9613477
TI  - Do general practices adhere to organizational guidelines for effective cervical
      cancer screening?
AB  - BACKGROUND: Well-organized cervical screening has been shown to be effective in
      the reduction of both morbidity and mortality from cancer of the uterine cervix.
      In The Netherlands, the GP plays an important role in the cervical screening. The
      question is whether the general practices are able to organize an effective
      cervical cancer screening. OBJECTIVES: We explored the extent to which Dutch
      general practices adhere to organizational guidelines for effective population
      based prevention of cervical cancer and which practice characteristics are
      important for this adherence. METHODS: A postal survey was conducted in a random
      sample of one-third of all 4758 Dutch general practices. Two sets of information
      were collected: practice characteristics and adherence to four organizational
      guidelines for effective cervical screening concerning inviting the women,
      monitoring attendance and sending reminders, organizing the taking of the smear
      and follow-up monitoring. RESULTS: A total of 1251 (79%) general practices
      returned a questionnaire; 90 questionnaires were excluded from analyses owing to
      missing data. The 1161 practices were representative of the Netherlands. A
      minority of the practices adhered to the four guidelines (in total, ten
      recommendations). The presence of the practice characteristics 'a general
      practice-based inviting system', 'a high delegation index' (delegating many tasks
      to the assistants) and a 'computerized patient information recording system' were
      positively associated with the adherence to most of the guidelines. CONCLUSION:
      This study showed that most of the Dutch general practices are not yet ready to
      organize an effective cervical cancer screening system. A general practice-based
      inviting system, a high delegation index and a computerized patient information
      recording system proved to be important for the adherence to the guidelines. In
      order to organize a cervical screening programme to achieve optimal
      effectiveness, emphasis should be placed on the adherence to the four guidelines
      described in this study and on stimulating a general practice-based inviting
      system, delegation to the practice assistant and computerization.

PMID- 9613478
TI  - Cost-effectiveness of a new treatment for somatized mental disorder taught to
      GPs.
AB  - BACKGROUND: Patients with mental disorder presenting with medically unexplained
      symptoms (somatized mental disorder) are difficult to treat and consume a lot of
      health care. OBJECTIVES: The aim of the study was to examine the cost
      effectiveness of a training package for somatized mental disorder delivered by
      GPs. METHODS: The study design was a prospective, before- and after-training
      study of different cohorts of patients attending eight GPs, acting as their own
      controls. Cost-effectiveness analysis was estimated using changes in case level
      on a self-rated psychiatric symptom questionnaire (GHQ-12) and direct health
      costs between the index consultation and 3 months later. RESULTS: There were 103
      and 112 patients with somatized mental disorder in the before and after training
      cohorts, respectively. After training, costs of referrals outside the primary
      care team decreased significantly by 23%, with little overall change in primary
      care costs. Total direct health care costs, including training, were reduced by
      15%. After training, an extra 17 patients were successfully treated (no longer
      GHQ-12 cases) at 3 months. The marginal cost-effectiveness per extra successfully
      treated patient was pound sterling 325 and the cost per successfully treated case
      was 69% of the cost of the GP's usual treatment. CONCLUSIONS: Training GPs with
      the reattribution training package appears to be extremely cost-effective.

PMID- 9613479
TI  - Chronic low back pain in primary care: a prospective study on the management and
      course.
AB  - BACKGROUND: There is little evidence about the management and course of chronic
      low back pain in primary care. OBJECTIVES: Our aim was to describe the course of
      chronic low back pain and the performed diagnostic and therapeutic procedures for
      patients with chronic low back pain in general practice. METHODS: Twenty-six GPs
      involved in the Registration Network Family Practices participated in this
      prospective follow-up study. All patients and GPs were asked to complete
      questionnaires at baseline and at 4, 8 and 12 months follow-up. RESULTS: The GPs
      provided information about diagnostic and therapeutic procedures concerning 524
      patients with chronic low back pain. Diagnostic tests other than history-taking
      and physical examination were not frequently used. Medication, mostly NSAIDs, was
      the most frequently used type of treatment (21.6%). The most frequent referrals
      concerned physiotherapy (16.3%) and neurology or neurologic surgery (6.3%).
      Information about the course of their chronic low back pain was provided by 368
      patients participating in our study. The course of chronic low back pain appeared
      to be quite stable, as there was only a slight improvement in pain intensity and
      physical functioning over the 12 months of follow-up. CONCLUSIONS: A variety of
      options for the treatment and referral of chronic low back pain patients is
      available for and used by GPs. Efforts should be made to establish which
      diagnostic and therapeutic procedures are the most effective for chronic low back
      pain.

PMID- 9613480
TI  - Aspects of diagnosis of acute otitis media.
AB  - BACKGROUND: Acute otitis media is a common disease, particularly among children.
      The importance of a correct diagnosis is crucial, especially as unjustified
      prescription of antibiotics has become a major problem in clinical praxis.
      OBJECTIVES: Our aim was to evaluate the predictive value of different otological
      findings in diagnostics and treatment of acute otitis media among GPs and ear
      specialists and to investigate if the diagnosis could be improved by the use of
      an ear microscope instead of an otoscope. Furthermore, we aimed to test the value
      of following an algorithm, METHODS: Thirty-one patients with otalgia at the
      Emergency Department at the Karolinska Hospital in Stockholm were examined by
      both a GP and an ear specialist. The GP used an otoscope, whereas the ear
      specialist first used an otoscope and then an ear microscope. The doctors
      registered their findings and their proposal for treatment in questionnaires. The
      ability among participating ear specialists to give a correct diagnosis was
      confirmed by the use of 12 video-taped selected cases of aural diseases. An
      algorithm for diagnostics, based on medical facts, was formulated and tested.
      RESULTS: In general, the concordance between ear specialists and GPs was
      satisfactory with regard to establishing the diagnosis acute otitis media. The
      diagnostics were not improved by use of an ear microscope. The algorithm
      identified most patients with acute otitis media. Conclusion. The results
      indicate that the following of a simple algorithm may simplify the CONCLUSION:
      and lead to a correct diagnosis of acute otitis media.

PMID- 9613481
TI  - Improving influenza vaccination coverage among high-risk patients: a role for
      computer-supported prevention strategy?
AB  - BACKGROUND: Worldwide, population-based influenza vaccination strategies are
      being developed to trace, immunize and monitor high-risk persons efficiently.
      Computerized prevention modules may facilitate such a strategy in general
      practice. OBJECTIVES: We established the applicability of a computerized
      influenza prevention module and specifically addressed improvement of
      immunization coverage in high-risk patients during two consecutive influenza
      vaccination rounds after introduction of the module. METHODS: In this descriptive
      study, four computerized practices of the Utrecht General Practices Network,
      covering about 36000 patients, participated. In 1995, all patients with high-risk
      diseases were traced by relevant tags, ICPC- and ATC-codes, using the module.
      According to changed Dutch immunization guidelines in 1996, healthy elderly
      people over 65 years were also traced. Demographical and medical data included
      age, high-risk disease and vaccine uptake. RESULTS: In October 1995, 3871 high
      risk patients were identified (11% of population); overall vaccination coverage
      was 68%. Over one-third of these patients had not been indicated before. In
      between the two vaccination rounds, 1104 previously unknown patients with high
      risk disease <65 years were found by means of the module's on-line status. In
      October 1996, 6889 persons, including 2308 healthy elderly, were indicated (19%),
      and vaccination coverage was 62%. Of 3477 patients whose high-risk diseases were
      documented in both vaccination rounds, an overall improvement of vaccination
      coverage from 71 % in 1995 to 76% in 1996 was observed (P < 0.05). Main
      improvements were found in elderly patients. Immunization rates were highest in
      those with more than one risk factor, lung or cardiac disease, and lowest in
      healthy elderly and patients under 65 years with lung, renal or other diseases.
      CONCLUSION: Computerized prevention modules and CMRs may facilitate population
      based prevention of influenza and the use should be further encouraged.

PMID- 9613482
TI  - Primary care anticoagulant clinic management using computerized decision support
      and near patient International Normalized Ratio (INR) testing: routine data from
      a practice nurse-led clinic.
AB  - BACKGROUND: Increasing indications for warfarin therapy has led to increased
      pressure on primary care to undertake therapeutic monitoring. OBJECTIVE: This
      study evaluates a primary care model of oral anticoagulation monitoring which
      utilises computerized decision support (CDSS) and near patient testing (NPT)
      within a practice nurse-led clinic. Whilst this has been shown to be a successful
      model under trial conditions, this paper reports the first data from a long
      standing clinic, outside a formal study. METHOD: A prospective evaluation of
      therapeutic and clinical control of all patients taking warfarin within one inner
      city general practice. Data were collected via CDSS. RESULTS: 29 patients were
      seen in 208 appointments. The mean percentage of patients within therapeutic
      range was 72%. The costs to the practice were pound sterling 1751. The costs the
      practice would have incurred had these patients been seen at the hospital with
      the same frequency would have been pound sterling 2290. CONCLUSIONS: The use of
      CDSS and NPT for nurse-delivered oral anticoagulation monitoring could enable the
      safe transfer of the majority of patients from secondary to primary care. Funding
      mechanisms to support the transfer of costs will be essential for most practices,
      as will be the maintenance of adequate staff training and quality assurance.

PMID- 9613483
TI  - Perceived gender differences in physician consulting behaviour during internal
      examination.
AB  - OBJECTIVE: Our aim was to investigate gender-related differences in consulting
      behaviour among family doctors in Belgium. METHODS: The study was conducted among
      32 family physicians and 303 patients. The family physician consulting behaviour
      was studied during consultations which included either an anal or a vaginal
      examination on three dimensions: a cure dimension, a care dimension and a
      dimension of consulting behaviour specific for consultations which included an
      internal examination. RESULTS: It was found that female family physicians were
      perceived by both male and female patients as showing more cure behaviour during
      consultations which included an anal examination. Female family doctors were also
      perceived as showing significantly more cure behaviour, more care behaviour and
      more consulting behaviour specific for an internal examination during
      consultations which included a vaginal examination. Furthermore, it was found
      that less-well-educated patients perceived more care behaviour during
      consultations which included an anal examination than did better-educated
      patients. Finally, less-well-educated patients perceived more cure behaviour and
      more behaviour specific for an internal examination in their doctor's consulting
      behaviour during consultations which included a vaginal examination.

PMID- 9613484
TI  - Childhood asthma: parents' perspective--a qualitative interview study.
AB  - OBJECTIVE: We aimed to describe the parents' perspective of their child's
      asthmatic disease, and relate it to the dialogue with the doctors and the
      diagnostic delay. METHODS: Qualitative studies with semi-structured interviews
      were carried out with 20 parents of 30 asthmatic children aged from 2 to 15 years
      who had had asthma for at least 1 year and were all attending a Copenhagen
      outpatient asthma clinic. RESULTS: The asthma symptoms, for most of the children
      starting during their first year, were manifold and complex, including long
      lasting coughing as a frequent symptom. Parents recognized specific asthma
      patterns in their child, often including behaviour change. Many parents had
      difficulty in understanding why doctors changed the dose of medicine. The
      diagnostic delay was significant. The study indicated problems in doctor-patient
      communication: differences in the conceptual vocabulary; the doctor's reluctance
      to consider the patient's story and rely instead on auscultation; as well as
      unexpected odd differential diagnoses. All contributed to the disturbed mutual
      understanding. CONCLUSION: The new asthma definition from the First International
      Pediatric Consensus Report is a milestone because it focuses on the patient's
      story and emphasizes the chronic episodic course rather than asthma as attacks.
      The study highlights the importance of "listening to the parents" in order to
      make the diagnosis and to secure parents' participation in starting anti
      inflammatory therapy, as well as regulating drug doses according to the symptoms,
      to secure the lowest possible but effective drug doses.

PMID- 9613485
TI  - Referrals of patients by family physicians to consultants: a survey of the
      Israeli Family Practice Research Network.
AB  - OBJECTIVE: We aimed to analyse factors influencing referral of patients by
      primary care physicians to specialist consultants at the beginning of the era of
      direct access to specialists in Israel. METHODS: We carried out a study of
      referrals by family physicians to specialists over a continuous period of 3
      months. Twenty-four certified family physicians filled in a questionnaire
      detailing referrals during the study period. All patients were referred for
      consultation to a specialist at regional speciality clinics or hospital out
      patient departments. RESULTS: Ten physicians met the study conditions. In 1140 of
      10896 (10.5%) visits, patients were referred to specialist consultants. The
      percentage of referral ranged from 7.4 to 15.9%. The difference between the
      physicians with the lowest and highest rates of referral was statistically
      significant (P < 0.0001). The variance in referral rates was not explained by
      significant differences in physician or practice variables. The types of
      specialists to whom the most referrals were made were orthopaedic surgeons,
      ophthalmologists, dermatologists, ear, nose and throat, general surgeons and
      plastic surgeons. There was a significant correlation between the type of
      specialist and the age of the patient. Older patients were referred more
      frequently to urologists, cardiologists and ophthalmologists, while younger
      patients were referred more frequently to ear, nose and throat specialists and
      gynaecologists (P < 0.01). CONCLUSIONS: The results of this study can be used as
      an aid for decision makers in the health services for determining policy. Direct
      access to some specialties might be appropriate, but not to all. Adoption of a
      policy based on these findings could lead to reduced health care costs by
      reducing the burden on hospital emergency rooms. It might also increase patient
      satisfaction in that the patients will have greater freedom of choice. On the
      other hand, more appropriate training of family physicians and more extensive
      self- and peer-quality assurance will increase the primary physician's knowledge
      and ability to diagnose and treat a broad range of problems and improve the level
      of care.

PMID- 9613486
TI  - A comparison of a Patient Enablement Instrument (PEI) against two established
      satisfaction scales as an outcome measure of primary care consultations.
AB  - OBJECTIVES: We aimed to compare a new primary care outcome measure-the Patient
      Enablement Instrument (PEI)-against two established satisfaction measures [the
      Medical Interview Satisfaction Scale (MISS) and the Consultation Satisfaction
      Questionnaire (CSQ)]. Specifically, we sought (i) to test whether enablement and
      satisfaction are related or separate concepts; and (ii) to assess whether the
      internal consistency of the PEI might be enhanced by the inclusion of items from
      the satisfaction instruments. METHODS: Questionnaire forms containing the three
      instruments in a variety of combinations were distributed to a total of 818
      patients attending for routine surgery consultations in three urban general
      practices of varying socio-economic mix. The main outcome measures were: scores
      on the PEI; scores on the CSQ, the MISS and their individual components; rank
      correlations between scores on the PEI and scores on the CSQ, the MISS and their
      component subscales; and Cronbach's alpha coefficient for the PEI. RESULTS:
      Overall mean scores, expressed as percentages of maximum scores attainable, were
      44.1% for the PEI, 76.9% for the CSQ and 77.6% for the MISS. Rank correlations
      between PEI scores and scores for the complete CSQ and MISS instruments were 0.48
      (P < 0.01) and 0.47 (P < 0.01), respectively. Correlations of PEI scores with
      individual component scores on the CSQ were generally lower and ranged from 0.14
      to 0.53; correlations of PEI scored with MISS component scores were also
      generally lower and ranged from 0.21 to 0.53. Internal consistency of the PEI
      items (assessed by Cronbach's alpha coefficient) was lowered when items from the
      CSQ or MISS were added. CONCLUSIONS: The study shows that 'enablement' is a
      primary care outcome measure which is related to but is different from general
      satisfaction.

PMID- 9613488
TI  - Recommendations and policy from the second World Rural Health Congress.

PMID- 9613487
TI  - Complex health problems in general practice: do we need an instrument for
      consultation improvement and patient involvement? Theoretical foundation,
      development and user evaluation of the Patient Perspective Survey (PPS).
AB  - BACKGROUND AND OBJECTIVES: Many patients in general practice present with complex
      health problems. It is argued that the GP who is in a prime position to counsel
      patients with such problems, will, however, often perceive a lack of tools to
      manage them. The aim of the present study was to develop a novel instrument in
      terms of a patient-administered questionnaire, the Patient Perspective Survey
      (PPS), designed to enhance the quality of clinical communication in the
      consultation. It is based on a biopsychosocial patient perspective, patient
      centredness, patient resources, involvement and coping, and quality of life
      orientation. METHODS: Development of the PPS has included comprehensive
      literature research, discussions and advice, during several phases, from groups
      of GPs, patients, broad panels of experts and testing in pilot studies. After
      many revisions, a 102-item version, consisting of a main somatic, mental and
      social domain axis, was evaluated by GPs and patients in 213 consultations.
      RESULTS: The basic idea, theoretical elements and purpose of the PPS appeared in
      general to be well accepted. Seventy-five to eighty-five per cent of the patients
      found the questions relevant and easy to understand and there were high positive
      scorings regarding influence on the doctor-patient relationship, communication,
      resource and coping aspects, occurrence of new information and general
      satisfaction with the consultation. Similar scorings were obtained from the GPs'
      evaluation. Both parties agreed that there is a need for a shorter and more
      specific PPS version, and that the resource and coping dimension should be even
      more extended. CONCLUSIONS: We consider it well documented that there is a need
      for this new instrument to deal with complex health problems in general practice,
      and that it has promising potentials for consultation improvement.

PMID- 9613489
TI  - Cerebral gangliogliomas: preoperative grading using FDG-PET and 201Tl-SPECT.
AB  - PURPOSE: To date there have been only scattered case reports comparing the
      nuclear medicine characteristics of gangliogliomas with their histologic grade.
      We sought to determine the relative usefulness of nuclear medicine scanning, CT,
      and MR imaging in predicting the histologic grade of these tumors. METHODS:
      Eleven cases of pathologically proved ganglioglioma were analyzed
      retrospectively. Preoperative positron emission tomography with 18
      fluorodeoxyglucose (FDG-PET), thallium chloride Tl 201 single-photon emission
      computed tomography (201Tl-SPECT), CT, and MR imaging studies were reviewed and
      compared with histologic tumor grade. FDG-PET scans were inspected visually for
      tumor metabolic activity relative to activity of normal gray and white matter.
      201Tl-SPECT scans were analyzed for tumor activity using regions of interest and
      activity ratios. CT and MR studies were reviewed for the presence of conventional
      radiologic features of malignancy (ie, enhancement and edema). RESULTS: Eleven
      patients had a total of 15 nuclear scans. Eight of nine gangliogliomas scanned
      with FDG-PET showed tumor hypometabolism, the ninth was normal. All nine were low
      grade gangliogliomas. Increased 201Tl-SPECT activity was seen in two high-grade
      gangliogliomas. The third 201Tl-SPECT scan, of a low-grade ganglioglioma, was
      normal. CT and MR studies showed enhancement in four gangliogliomas, of which two
      were high grade and two low grade. Edema was seen only in conjunction with the
      two high-grade gangliogliomas. CONCLUSION: FDG-PET and 201Tl-SPECT are 100%
      correlative in preoperative prediction of histologic grade of ganglioglioma.
      Tumors with decreased or normal PET or SPECT activity were low grade; tumors with
      increased SPECT activity were high grade. These results may be more reliable than
      CT and MR imaging findings in assessing tumor grade, and they may be of value for
      surgical planning and determining patient prognosis.

PMID- 9613490
TI  - Gangliogliomas: ubiquitous or not?

PMID- 9613491
TI  - Gangliogliomas: issues of prognosis and treatment.

PMID- 9613492
TI  - Preoperative grading of gangliogliomas using FDG PET and Tl-201 SPECT: comments
      from a nuclear medicine view.

PMID- 9613493
TI  - MR differential diagnosis of normal-pressure hydrocephalus and Alzheimer disease:
      significance of perihippocampal fissures.
AB  - PURPOSE: In the older patient with dilated ventricles, it is often difficult to
      differentiate normal pressure hydrocephalus (NPH) from cerebral atrophy caused by
      Alzheimer disease (AD). This study was undertaken to see if dilatation of the
      perihippocampal fissures (PHFs) could be used as a distinguishing characteristic
      of these two disorders. METHODS: MR images of 17 patients with AD were compared
      with those from an equal number of patients with NPH who improved after
      ventriculoperitoneal shunting. The PHFs, lateral ventricles, third ventricle, and
      temporal horns were graded subjectively. Objective, computer-aided volumetric
      measurements of the PHFs and lateral ventricles were obtained. The preshunt
      images of the NPH patients were evaluated. RESULTS: Significant differences
      between the two groups were found for the PHFs and lateral ventricles by both the
      subjective and objective methods, with a high degree of correlation between the
      two methods. CONCLUSION: The degree of dilatation of PHFs appears to be a
      sensitive and specific marker for differentiating AD from NPH by both subjective
      and objective means, with a very small overlap between the two groups. This
      observation may have relevance in day-to-day practice.

PMID- 9613494
TI  - Comparison of single- and triple-dose contrast material in the MR screening of
      brain metastases.
AB  - PURPOSE: Although studies obtained with triple-dose contrast administration can
      show more brain metastases than those obtained with single-dose contrast material
      in patients with multiple metastases, such studies are costly and of limited
      clinical benefit. Since most patients who undergo screening have negative
      findings or a single metastasis, this study was performed to compare the clinical
      utility of single-dose versus triple-dose contrast administration in this large
      group of patients who could benefit from the possible increased sensitivity in
      lesion detection. METHODS: Ninety-two consecutive patients with negative or
      equivocal findings or a solitary metastasis on single-dose contrast-enhanced MR
      images underwent triple-dose studies. Findings were compared with a standard of
      reference composed of panel review and long-term follow-up. Further analysis was
      performed by comparing results with those obtained by two blinded readers.
      RESULTS: In all 70 negative single-dose studies, the triple-dose studies depicted
      no additional metastases in terms of the standard of reference. No statistically
      significant difference was seen between the results of the single- and triple
      dose studies. For 10 equivocal single-dose studies, the triple-dose study helped
      clarify the presence or absence of metastases in 50% of the cases. In 12 patients
      with a solitary metastasis seen on the single-dose study, the triple-dose study
      depicted additional metastases in 25% of the cases. In the results of one of the
      two blinded readers, use of triple-dose contrast led to a statistical difference
      by decreasing the number of equivocal readings but at the expense of increasing
      the number of false-positive readings. CONCLUSION: Routine triple-dose contrast
      administration in all cases of suspected brain metastasis is not helpful. On the
      basis of our investigation, we conclude that the use of triple-dose contrast
      material is beneficial in selected cases with equivocal findings or solitary
      metastasis, although with the disadvantage of increasing the number of false
      positive results.

PMID- 9613495
TI  - Neuroradiologic screening for brain metastases--can quadruple dose gadolinium be
      far behind?

PMID- 9613496
TI  - Helical CT for the follow-up of cervical internal carotid artery dissections.
AB  - PURPOSE: The aim of this study was to assess the changes over time of internal
      carotid artery (ICA) dissections by using helical CT. METHODS: Twenty-seven
      patients with 30 angiographically proved ICA dissections were followed up with
      helical CT at 7 to 62 months (median, 24 months) after conventional angiography.
      CT scans, analyzed independently by two radiologists in a blinded fashion, were
      evaluated for the presence of mural thickening, aneurysmal formation, and
      arterial occlusion. In cases without persisting occlusion or aneurysm, we
      measured the external diameter of the ICA at its upper segment. RESULTS: The
      interobserver agreement was good. Mild mural thickening was observed in four
      cases of 30 previously dissected ICAs. All stenotic and nearly occlusive
      dissections without an aneurysm (n = 12) reverted to a normal or nearly normal
      diameter. Half the aneurysms resolved spontaneously (four of eight). Of the 10
      occluded ICAs, nine were recanalized, but their external diameter was
      significantly smaller than that of normal carotid arteries, and a hypoplastic
      appearance was seen throughout the cervical segment of the ICA in three cases.
      CONCLUSION: Most arterial lesions tend to improve or disappear spontaneously, but
      persisting ICA narrowing may be observed in the late course of occlusive-type
      dissections.

PMID- 9613497
TI  - The predictive value of early CT and angiography for fatal hemispheric swelling
      in acute stroke.
AB  - PURPOSE: Our goal was to analyze the predictive value of early CT and
      arteriographic morphologic criteria to achieve a more reliable prediction of
      fatal outcome in patients undergoing fibrinolytic stroke treatment. METHODS: In
      74 patients with acute carotid artery stroke, early signs of cerebral ischemia
      were determined by CT. The site of vascular occlusion was identified by digital
      subtraction angiography (DSA). The patients were subsequently treated by
      intraarterial (n = 68) or intravenous (n = 6) fibrinolysis by means of
      recombinant tissue plasminogen activator (rt-PA), urokinase, or rt-PA combined
      with lys-plasminogen and followed-up for a period of 3 months. CT and DSA data
      were compared with the clinical course, with special emphasis on signs of early
      fatal deterioration (ie, death by intracranial mass effect) as determined by
      corresponding CT and clinical observations, occurring within 7 days after stroke.
      RESULTS: Seventeen patients died, all of intracranial mass effect, and all within
      a week after stroke. In nine of these fatalities, DSA revealed carotid "T"
      occlusion (CTO), which affected 19 patients. In five of the fatalities, a major
      early sign of ischemia (MESI, referring to cortical hypodensity in more than a
      third of the territory of the middle cerebral artery, as seen in 14 patients) was
      recognizable on the initial CT scan. This led to a higher predictive value and
      sensitivity of CTO relative to MESI for estimating early fatality. CONCLUSION:
      CTO as determined by DSA is a substantially better predictor of fatal outcome in
      patients undergoing intraarterial thrombolytic therapy than is MESI as determined
      by CT.

PMID- 9613498
TI  - Mapping of the central sulcus with functional MR: active versus passive
      activation tasks.
AB  - PURPOSE: Our purpose was to assess the pattern of functional MR activation
      obtained with a passive sensory versus an active sensorimotor hand stimulus
      paradigm. METHODS: Eight functional MR runs, four with an active sensorimotor
      (sponge-squeezing) task and four with a passive sensory (palm-finger brushing)
      reception, were acquired for each of 10 healthy volunteers. Activation maps were
      generated by thresholding cross-correlation maps. Regions of interests (ROIs)
      were drawn around the precentral and postcentral gyri on T1-weighted images
      according to established anatomic criteria, and the number of activated pixels
      inside the ROIs was ascertained. Displacement of the sensorimotor and sensory
      activation centroids within the ROIs from the central sulcus as well as from each
      other was measured. RESULTS: Active sensorimotor stimulation produced a
      significantly greater number of activation pixels than did passive sensory
      stimulation. Run-to-run variability was equivalent between sensorimotor and
      sensory activation tasks. On average, the sensorimotor and sensory activation
      centroids were located in the postcentral gyrus, and their spatial locations were
      not significantly different. CONCLUSION: Active and passive activation tasks
      produce largely equivalent results. Presurgical mapping of the sensorimotor area
      can be performed with functional MR imaging using a passive palm-finger brushing
      task in patients who are physically unable to perform active finger-tapping or
      hand-squeezing sensorimotor activation tasks.

PMID- 9613499
TI  - Sex and electroencephalographic synchronization after photic stimulation predict
      signal changes in the visual cortex on functional MR images.
AB  - PURPOSE: We evaluated factors that influence MR signal changes during photic
      stimulation of the visual cortex. We also tested the hypothesis that functional
      MR imaging response corresponds to electroencephalographic (EEG) synchronization
      after photic stimulation. METHODS: Thirty-eight healthy subjects, 20 men and 18
      women, underwent photic stimulation of the visual cortex. They were studied with
      a 1.5-T MR unit, and photic stimulation was induced via 8-Hz LED goggles. Seven
      subjects with and seven without detectable functional MR imaging response to
      photic stimulation underwent further studies with 16-channel EEG after 2- to 30
      Hz stroboscopic stimulation. RESULTS: Thirteen men and 18 women had a significant
      increase in MR signal in the visual cortex; seven men showed no visual cortex
      activation during more than two repeated studies. Six of seven volunteers with
      increased functional MR imaging signal after photic stimulation also showed signs
      of EEG synchronization when an 8-Hz stroboscopic flash was used; six of seven
      subjects with no functional MR imaging lacked EEG synchronization at 8-Hz
      stimulation. CONCLUSIONS: Men were more likely than women to have undetectable MR
      signal changes after photic stimulation. This finding should be considered when
      interpreting results of functional MR imaging studies. EEG with stroboscopic
      examination is a good predictor of functional MR imaging sensitivity to changes
      in regional cerebral blood flow induced by sensory stimulation.

PMID- 9613500
TI  - Diffusion-weighted MR imaging in hypertensive encephalopathy: clues to
      pathogenesis.
AB  - PURPOSE: Hypertensive encephalopathy, a complex of cerebral disorders, including
      headache, seizures, visual disturbances, and other neurologic manifestations, is
      associated with a variety of conditions in which blood pressure rises acutely. It
      has been ascribed to either exuberant vasospasm with ischemia/infarction or
      breakthrough of autoregulation with interstitial edema. Diffusion-weighted MR
      imaging may be used to determine whether the edema in hypertensive encephalopathy
      is cytotoxic or vasogenic in origin. METHODS: Diffusion-weighted imaging was
      performed using the double line scan diffusion imaging technique on a 1.5-T MR
      system. Seven patients with hypertensive encephalopathy were imaged within 1 day
      of the onset of their symptoms. Apparent diffusion coefficient maps as well as
      low and high b-factor images were acquired. The two-tailed paired Student's t
      test was used to compare the apparent diffusion coefficients in edematous brain
      regions with those of normal white matter. RESULTS: In all cases the apparent
      diffusion coefficient maps of the patients with hypertensive encephalopathy
      showed increased signal in regions corresponding to increased T2 signal on
      standard T2-weighted (low b-factor) images. Quantitative apparent diffusion
      coefficients in regions of abnormal T2 signal were 1.36 +/- 0.14 microm2/ms,
      compared with 0.80 +/- 0.05 microm2/ms in normal white matter. Diffusion-weighted
      (high b-factor) T2-weighted images did not show abnormal signal. CONCLUSION:
      Diffusion-weighted MR imaging shows that the edema in hypertensive encephalopathy
      is of vasogenic origin and does not represent ischemia or infarction. This
      finding may have therapeutic implications.

PMID- 9613501
TI  - Hemichorea-hemiballism: an explanation for MR signal changes.
AB  - PURPOSE: Some cases of hemichorea-hemiballism (HCHB) are associated with a
      hyperintense putamen on T1-weighted MR images, the cause of which remains
      unclear. Our purpose was to determine the cause and significance of these MR
      signal changes. METHODS: We analyzed the clinical and neuroimaging findings in 10
      patients with HCHB, focusing on locations of the hyperintense lesions on T1
      weighted images, comparing them with those on CT scans, and evaluating their
      changes after years of follow-up. A biopsy was performed in one patient. RESULTS:
      Seven patients had hyperglycemia and two had cortical infarcts. HCHB recurred in
      four patients. A hyperintense putamen preceded the occurrence of HCHB in two
      patients. T1-weighted MR images revealed hyperintense lesions limited to the
      ventral striatum in six patients. Hyperintense lesions extended to the level of
      the midbrain in one patient and persisted for as long as 6 years in another
      patient. T2-weighted MR images revealed slit-shaped cystic lesions in the lateral
      part of the putamina 2 to 6 years after the onset of symptoms in two patients. A
      biopsy specimen from the hyperintense putamen in one patient revealed a fragment
      of gliotic brain tissue with abundant gemistocytes. Proton MR spectroscopy of the
      specimen showed an increase in lactic acid, acetate, and lipids, and a decrease
      in N-acetylaspartate and creatine, suggesting the presence of pronounced energy
      depletion and neuronal dysfunction. CONCLUSION: Gemistocytes are sufficient to
      explain the shortening of T1 relaxation time. Our investigation suggests that
      neurons in the ventral striatum and striatonigral pathway may play a critical
      role in generating ballism.

PMID- 9613502
TI  - MR of cerebral malaria.
AB  - In three cases of cerebral malaria, MR imaging disclosed either cortical infarcts
      (one case) or hyperintense areas of white matter (two cases) on T2-weighted and
      fluid-attenuated inversion-recovery sequences. These white matter abnormalities
      were, in one case, sharply limited, symmetrical, hyperintense, and unenhanced; in
      the other case, they were diffuse, hyperintense, and had a more limited focus.
      The diffuse hyperintensity was probably due to edema, whereas focal lesions were
      probably associated with gliosis.

PMID- 9613503
TI  - Colloid cyst of the third ventricle: sometimes more conspicuous on CT than MR.
AB  - We present two cases of surgically proved colloid cysts that were more apparent
      on CT scans than on MR images. These cysts, while hyperdense on CT scans, were
      nearly isointense with brain on multiple MR sequences. This relative lack of
      visibility represents a potential pitfall when imaging a patient with headache.

PMID- 9613504
TI  - MR of spinal cord ganglioglioma.
AB  - PURPOSE: Our purpose was to describe the MR imaging features in a series of
      spinal intramedullary gangliogliomas and to compare these findings with the MR
      features of intramedullary astrocytomas and ependymomas. METHODS: A retrospective
      analysis was performed of 76 MR examinations in 27 patients with histologically
      proved spinal ganglioglioma; these were then compared with imaging findings in a
      representative sample of histologically proved spinal cord astrocytomas and
      ependymomas. RESULTS: Statistically significant observations regarding spinal
      gangliogliomas included young age of the patients (mean, 12 years), long tumor
      length, presence of tumoral cyst, presence of bone erosion and scoliosis, absence
      of edema, presence of mixed signal intensity on T1-weighted images, and presence
      of patchy enhancement and cord surface enhancement. A trend (not statistically
      significant) was noted for holocord involvement and lack of magnetic
      susceptibility. CONCLUSION: Spinal ganglioglioma can be strongly suspected if MR
      images reflect the above criteria; however, the ultimate diagnosis still depends
      on radical resection and appropriate histopathologic investigation.

PMID- 9613505
TI  - Contrast media of high and low molecular weights in the detection of recurrent
      herniated disks.
AB  - PURPOSE: Our goal was to compare contrast enhancement of recurrent herniated disk
      fragments and scar after intravenous injection of a new high-molecular-weight
      contrast medium, Gadomer 17 (gadomer), with that after injection of a low
      molecular-weight contrast medium, (gadopentetate dimeglumine). METHODS: Recurrent
      herniated disks were modeled in dogs by placing a fragment of intervertebral disk
      cartilage in the epidural space at laminectomy. MR imaging was performed with one
      of the contrast media at 20 and 50 days and with the other medium at 22 and 52
      days. The changes in signal intensity from baseline in the disk fragment and in
      the adjacent scar tissue was measured at 2, 22, and 45 minutes. Differences were
      tested for significance with a student t-test. RESULTS: At 50 days after surgery,
      signal intensity in the intervertebral disk fragment increased by an average of
      0.52 at 2 minutes after injection of gadomer and by an average of 0.90 after
      injection of gadopentetate. For scar, the increases in signal intensity were 1.41
      (gadomer) and 1.62 (gadopentetate). At 22 and 45 minutes after injection, the
      signal intensity change in the disk fragment continued to be significantly
      greater after gadopentetate than after gadomer injection. In comparison with the
      changes at 50 days, both scar and disk fragment tended to show greater signal
      intensity changes at 20 days. Signal intensity changes in the disk fragments were
      significantly less after gadomer than after gadopentetate. Signal intensity
      changes in scar were slightly less with gadomer than with gadopentetate.
      CONCLUSION: Greater contrast is achieved between scar and recurrent herniated
      disk with a higher-molecular-weight contrast medium than with one of lower
      molecular weight. The difference between the high- and low-molecular-weight
      contrast media increases with maturation of the scar tissue.

PMID- 9613506
TI  - Myelopathy caused by nitrous oxide toxicity.
AB  - We describe a case of myeloneuropathy resulting from nitrous oxide abuse. MR
      imaging of the spine revealed symmetric abnormal signal in the posterior columns
      of the cervical cord. Myeloneuropathy is caused by inactivation of vitamin B12 by
      nitrous oxide. This syndrome can also be seen in patients with borderline vitamin
      B12 deficiency who have recently been anesthetized with nitrous oxide.

PMID- 9613507
TI  - Spinal intradural cerebellar ectopia.
AB  - An ectopic cerebellum, as in Chiari malformations and ectopic cerebellar
      dysplastic tissue, is a common finding; however, the presence of an organized
      ectopic cerebellum is exceedingly rare. We describe the MR imaging, surgical, and
      histologic appearance of an intraspinal ectopic cerebellum in an infant.

PMID- 9613508
TI  - MR of leptomeningeal spinal and posterior fossa amyloid.
AB  - We report an unusual cause of leptomeningeal MR enhancement, amyloid, along the
      surfaces of the spinal cord and brain stem and in the spinal subarachnoid space,
      with sacral intradural and epidural deposition. Type I familial amyloid
      polyneuropathy may cause amyloid deposition along the leptomeninges of the spinal
      cord and brain in addition to the visceral organs and the peripheral somatic and
      autonomic nerves.

PMID- 9613509
TI  - Giant cervical epidural veins after craniectomy for head trauma.
AB  - Markedly dilated cervical epidural veins and right upper extremity weakness
      developed in a 43-year-old man 4 months after contralateral craniectomy for head
      trauma. After cranioplasty, his symptoms improved markedly and the size of the
      veins returned to normal. These findings suggest that enlarged cervical epidural
      veins may occur without an underlying vascular lesion and that upper extremity
      weakness may occasionally be attributable to spinal cord venous stasis.

PMID- 9613511
TI  - Percutaneous direct-puncture acrylic embolization of a pseudoaneurysm after
      failed carotid stenting for the treatment of acute carotid blowout.
AB  - We report a difficult case of recurrent carotid blowout syndrome in a patient who
      had a rupture of the common carotid artery with formation of a large
      pseudoaneurysm. Conventional management of this emergency, consisting of
      composite occlusion of the internal and common carotid arteries, was not possible
      owing to prior clinical failure of balloon test occlusion. This led to an initial
      attempt to cover the site of rupture with overlapping self-expanding stents,
      which was only temporarily successful in controlling the hemorrhage. When a
      subsequent episode of carotid rupture with life-threatening hemorrhage occurred,
      percutaneous direct-puncture acrylic embolization with temporary flow arrest was
      used to successfully obliterate the pseudoaneurysm.

PMID- 9613510
TI  - Endovascular treatment of pseudoaneurysms with electrolytically detachable coils.
AB  - PURPOSE: We describe the clinical presentation, angiographic findings, and
      clinical outcome in a group of patients with pseudoaneurysms treated by a new
      endovascular technique using Guglielmi electrolytically detachable platinum coils
      (GDCs). METHODS: We retrospectively reviewed the angiographic and clinical
      findings in a series of 11 patients with pseudoaneurysms occurring in a variety
      of locations: seven in the cavernous carotid artery, one in the petrous carotid
      artery, two in the anterior cerebral artery, and one in the cervical vertebral
      artery. RESULTS: All aneurysms were cured with GDC embolization. The only
      complication was a branch occlusion, which resolved with heparinization and
      produced no clinical sequelae. CONCLUSION: Pseudoaneurysms can be safely and
      effectively treated by embolization with GDCs. Consideration needs to be given to
      the anatomic location of the pseudoaneurysm and the acuity of onset. Treatment
      efficacy may by improved if there are bony confines around the aneurysm or if
      therapy takes place in the subacute period, when the wall of the pseudoaneurysm
      has matured and stabilized.

PMID- 9613512
TI  - Embolization of intracranial aneurysms with Guglielmi detachable coils augmented
      by microballoons.
AB  - We describe two cases in which balloons were used to aid in the occlusion of
      intracranial aneurysms with Guglielmi detachable coils. In both patients, initial
      attempts to place coils within the aneurysmal sac failed, as the loops of the
      coil repeatedly protruded through a wide aneurysmal neck into the parent vessel.
      Temporary balloons placed across the neck of these small, wide-necked aneurysms,
      the bridging balloon technique, effectively narrowed the necks, providing support
      for the formation of a proper coil basket, which was not possible without the
      balloon. Follow-up studies at 1 year showed good results in both patients.

PMID- 9613513
TI  - Embolization of an orbital varix after surgical exposure.
AB  - We report a case of primary orbital varix treated by embolization with coils
      after surgical exposure and puncture of the venous ectasia. This method of
      treatment has the advantage of limiting traumatic dissection and avoiding
      difficult venous catheterization.

PMID- 9613514
TI  - The suboccipital carrefour: cervical and vertebral arterial anastomosis.
AB  - PURPOSE: Our objective was to anatomically define the anastomoses between
      cervical and carotid arterial distributions (the carrefour) in the rabbit and to
      assess the contribution of these collaterals to cortical blood flow (CBF) during
      cerebral ischemia. METHODS: Angiography was carried out in six rabbits with
      basilar artery occlusion using selective contrast injection into the right
      subclavian, external carotid, and internal carotid arteries. Anastomoses were
      corroborated with methacrylate vascular casts prepared in five additional
      rabbits. CBF was measured in eight rabbits by H2 clearance after basilar artery
      occlusion and again after bilateral common carotid artery occlusion. Cortical DC
      potential was measured during ischemia in these rabbits and in another 19 rabbits
      after additional occlusion of the cervical collateral arteries. RESULTS: A
      network of anastomoses between superficial and ascending cervical, superior
      intercostal, vertebral, and occipital arteries was found by angiography and
      corrosion casts. Additional communications in the ophthalmic, ethmoidal, and
      cerebellar arterial distributions are described. These pathways were found to
      supply a mean of 15 +/- 7 mL/100 g per minute residual CBF during three-vessel
      ischemia, or 24% of the preischemic CBF. Ischemic depolarization of DC potential
      occurred in seven of the eight rabbits with collateral CBF at a mean latency of
      2.64 +/- 0.59 minutes and at 1.71 +/- 0.09 minutes in those without. CONCLUSION:
      The suboccipital collateral network of the rabbit resembles that of humans and
      can contribute significantly to CBF during ischemia. The results suggest that
      this model may be useful for evaluating methods of optimizing hemodynamic control
      of the anastomoses in situations such as those encountered during endovascular
      therapy.

PMID- 9613515
TI  - Use of a guide catheter as a temporary stent during microcatheter intervention.
AB  - Placement of a guiding catheter through a tortuous, narrowed, or intrinsically
      small vessel may result in severe reduction or occlusion of blood flow. However,
      nonbraided guiding catheters can be simply modified with a catheter hole punch to
      create a temporary stent. The stent reestablishes blood flow, which is routed
      through the distal segment of the guiding catheter while maintaining the guide
      platform for the introduction of microcatheters and devices necessary to perform
      intervention.

PMID- 9613516
TI  - An organ-preserving selective arterial chemotherapy strategy for head and neck
      cancer.
AB  - PURPOSE: Squamous cancer of the upper aerodigestive tract is a disheartening
      disease. Despite our best efforts, the long-term survival rate remains only 15%
      to 40%, and surgical cures often decrease the quality of life owing to the loss
      of swallowing and speech organs. A better understanding of tumor dynamics and the
      discovery that thiosulfate can neutralize cisplatin led us to develop a treatment
      plan that combines a rapid superselective high-dose intraarterial delivery of
      cisplatin (CDDP), simultaneous intravenous infusion of its antagonist,
      thiosulfate, and radiation therapy. METHODS: Patients with advanced head and neck
      squamous cancer were entered into the protocol after a multidisciplinary
      evaluation that included CT or MR imaging. Forty-two patients constituted the
      first cohort. After baseline angiography, an arterial acceptance test determined
      the maximum infusion rate that the tumor's nutrient artery would accept. CDDP was
      then infused at that rate, usually within 3 to 5 minutes, while the antagonist
      thiosulfate was given intravenously. In the second cohort of 85 patients with
      stage 3 or 4 previously untreated and unresectable disease, local radiation was
      added to the treatment plan. The radiation dose (180-200 cGy/d x 35) was
      delivered regionally on the basis of the known radiosensitizing effect of CDDP.
      RESULTS: Cohort 1 allowed us to develop the infusion technique and to establish a
      dose quantity and delivery frequency. When 150 mg/m2 was administered weekly for
      4 weeks, no severe toxicity was found. In cohort 2, 72 (92%) of the remaining 78
      patients had complete disappearance of their tumor. Seventeen severe toxic events
      were associated with 323 femoral catheterizations. One patient died of pulmonary
      embolus, precluding follow-up evaluation. Six patients had neurologic sequelae,
      three with transient and three with permanent strokes. CONCLUSION: Rapid
      superselective chemotherapy with CDDP combined with a circulatory systemic
      antagonist allowed delivery of an antitumoral drug directly into the lesion while
      protecting the kidneys and bone marrow from the agent's systemic effects. Use of
      a dose regimen of 150 mg CDDP/m2 per week for 4 weeks resulted in the
      disappearance of a large percentage of advanced squamous cancers.

PMID- 9613517
TI  - Near-resonance saturation pulse imaging of the extraocular muscles in thyroid
      related ophthalmopathy.
AB  - PURPOSE: We examined the utility of near-resonance saturation pulse imaging
      (magnetization transfer [MT] and spin lock) in characterizing microstructural
      changes occurring in the extraocular muscles of patients with thyroid-related
      ophthalmopathy (TRO). METHODS: Eight healthy volunteers and 10 patients with TRO
      were imaged using an off-resonance saturation pulse in conjunction with
      conventional spin-echo T1-weighted imaging at frequency offsets of 500, 1000,
      1500, and 2000 Hz from water resonance. The relative contributions of MT and spin
      lock excitation to image contrast at each frequency offset were estimated using a
      computer simulation model. Suppression ratios were calculated for the control and
      TRO groups from measurements obtained on two successive coronal sections in the
      widest portion of the inferior and medial rectus muscles bilaterally. A repeated
      measures analysis of variance and a parametric correlation analysis were
      performed to evaluate maximum cross-sectional area, MR-generated signal, and
      suppression ratios for the extraocular muscles examined. RESULTS: Our computer
      model suggested that saturation of extraocular muscles was due to pure MT effects
      with our off-resonance pulse at 2000 and 1500 Hz, to a combination of MT and spin
      lock at 1000 Hz frequency offset, and, primarily, to spin-lock excitation at 500
      Hz frequency offset. Suppression ratios for the extraocular muscles of the TRO
      patients were significantly lower than that observed for the control subjects at
      1500, 1000, and 500 Hz frequency offset. This differential saturation effect was
      maximal at 500 Hz frequency offset, with mean suppression ratios for the inferior
      and medial rectus muscles of 27% for the healthy subjects and 20% for the TRO
      group. CONCLUSION: Both MT and spin-lock contrast of the extraocular muscles in
      patients with TRO differ significantly from that observed in control subjects.
      Near-resonance saturation pulse imaging may enhance our understanding of the
      microstructural changes occurring in the extraocular muscles of these patients.

PMID- 9613518
TI  - Isolated unilateral hypoglossal neuropathy caused by dural arteriovenous fistula.
AB  - We report a case of isolated hypoglossal nerve paralysis caused by a dural
      arteriovenous fistula. Diagnosis is discussed with emphasis on conventional and
      MR angiography. The anatomy of the hypoglossal nerve is reviewed along with more
      common causes of pathologic conditions.

PMID- 9613519
TI  - Primary malignant melanoma in the oral mucosal membrane with metastasis in the
      cervical lymph node: MR appearance.
AB  - We report a case of oral malignant melanoma with metastasis to the cervical lymph
      node. The MR appearance corresponded to previously reported MR characteristics of
      malignant melanoma in other regions. Both the primary tumor and the nodal
      metastasis showed high signal intensity on T1-weighted images.

PMID- 9613520
TI  - Gorlin syndrome: unusual manifestations in the sella turcica and the sphenoidal
      sinus.

PMID- 9613521
TI  - MR sialography using half-Fourier acquisition single-shot turbo spin-echo (HASTE)
      sequences.
AB  - We describe our preliminary experience with the half-Fourier acquisition single
      shot turbo spin-echo (HASTE) sequences for MR imaging of the salivary gland
      ducts. In the majority of patients, the main parotid and/or submandibular gland
      ducts and large branches within the glands were detectable on MR images obtained
      in 2 seconds per section and within 3 minutes for the entire examination. MR
      sialography using HASTE sequences can be combined with conventional MR studies
      for the salivary glands.

PMID- 9613522
TI  - Treatment of brain tumors in children is associated with abnormal MR
      spectroscopic ratios in brain tissue remote from the tumor site.
AB  - PURPOSE: Children who have brain tumors are at risk for a variety of treatment
      related sequelae, including neuropsychological and cognitive impairment,
      neurologic deficits, and neuroendocrinologic disturbances. We sought to determine
      the value of proton MR spectroscopy in assessing brain tissue remote from the
      tumor site to ascertain the effects of chemotherapy and radiation treatment in
      these patients. METHODS: Single-voxel proton MR spectra from 70 patients (111
      spectra) and 11 healthy volunteers (11 spectra) were analyzed. NAA/Cr, NAA/Cho,
      and Cho/Cr ratios based on peak areas were obtained from nonneoplastic regions of
      the frontal lobe. The relationship between MR spectroscopic ratios and treatment
      was determined. RESULTS: NAA-containing ratios were decreased in patients as
      compared with control subjects. The presence of gadolinium-based contrast
      material did not cause significant changes in the ratios as compared with
      precontrast data. When chemotherapy was a component of a child's treatment
      protocol, we found a significant decline in NAA/Cr ratios. Patients who underwent
      both chemotherapy and radiation therapy showed a trend toward lower NAA
      containing ratios if the chemotherapy was administered before the radiation
      therapy. Patients receiving whole-brain radiation had a trend toward lower NAA
      containing ratios than did those who had only focal tumor treatment. CONCLUSION:
      In children with brain tumors, MR spectroscopy of brain tissue remote from the
      tumor reveals treatment-related biochemical changes.

PMID- 9613523
TI  - MR features of developing periventricular white matter in preterm infants:
      evidence of glial cell migration.
AB  - PURPOSE: MR imaging of the brain is increasingly used in the investigation of the
      newborn, but little information is available on the normal appearance of the
      developing brain. We scanned a series of newborn infants in an attempt to define
      the normal appearance of developing periventricular white matter and to assess
      how pathologic conditions may modify this appearance. METHODS: Sixty-eight
      newborn infants, median postmenstrual age (PMA) 34 weeks (range, 24 to 42 weeks),
      were subdivided into two groups: group A (n = 33), which included those with
      normal clinical and sonographic examinations, and group B (n = 35), which
      contained those with evidence of neuroabnormality detected prior to the MR study,
      either clinically or by cerebral sonography. Images were acquired in two planes
      on a 1.5-T imager using turbo spin-echo pulse sequences. RESULTS: Symmetric
      periventricular bands of reduced signal intensity were noted in the frontal
      periventricular white matter on T2-weighted images in 98% of group A infants and
      in 97% of group B infants. The number of bands was inversely related to PMA. The
      reduction in number of bands with increasing PMA was delayed in group B infants.
      CONCLUSION: The uniform appearance of periventricular bands in a population of
      healthy infants and their relationship to the infants' maturity is consistent
      with the results of previous histologic studies. These studies demonstrate the
      presence of migrating glial cells within the periventricular white matter of
      infants beyond 20 weeks' gestation, when neuronal migration to the cortex is
      complete. We postulate that the bands seen on T2-weighted images represent groups
      of migrating glial cells, providing a further marker of cerebral maturation.

PMID- 9613524
TI  - Tectal tumors of childhood: clinical and imaging follow-up.
AB  - PURPOSE: This study was done to determine which clinical and imaging findings
      best correlate with outcome in children with tectal tumors. METHODS: A
      retrospective review was done of the medical records and imaging studies of 32
      children (16 boys and 16 girls; mean age, 8 years) with tectal tumors. Eight
      children had CT, 11 had MR imaging, and 13 had both CT and MR studies. Findings
      from surgical and pathologic reports as well as from follow-up examinations (mean
      follow-up period, 5 years; range, 3.6 months to 17 years) were included in the
      review. RESULTS: All patients had hydrocephalus and all but one required CSF
      diversion. The tectum was the center of the tumor in all cases and the majority
      of the tumors appeared isodense on CT scans, isointense on T1-weighted MR images,
      and hyperintense on T2-weighted images. Twenty patients required no further
      treatment. In this group, the mean maximum tumor diameter was 1.8 cm and
      enhancement occurred in two cases. At follow-up, 18 patients had stable tumor
      size, one had an increase in tumor size with cyst formation but no worsening of
      symptoms, and one had a decrease in tumor size. Twelve patients required further
      treatment (excision and/or radiotherapy) because of progression as indicated by
      either increased tumor size or worsening of symptoms. In this group, the mean
      maximum tumor diameter was 2.5 cm and contrast enhancement occurred in nine
      cases. Further follow-up in this group showed decreased tumor size in eight and
      stable residual tumor in three. CONCLUSION: Tectal tumors in childhood have
      variable behavior. MR imaging assists in the clinical determination of which
      children need treatment beyond CSF diversion. Larger tumor size and enhancement
      are radiologic predictors of the need for further treatment.

PMID- 9613525
TI  - MR of cerebellar cortical dysplasia.
AB  - MR imaging findings are described in four patients with cerebellar cortical
      dysplasia. Typically, cerebellar disorganized folia were seen as an irregular
      bumpy gray-white matter interface. In addition, cystlike cortical abnormalities
      were observed in two patients and associated supratentorial developmental
      abnormalities were seen in three patients. To our knowledge, cerebellar cortical
      dysplasia without supratentorial abnormalities, as seen in one patient, has not
      been reported before. We suggest that cerebellar cortical dysplasia represents a
      spectrum of abnormalities ranging from mild to extensive in severity.

PMID- 9613526
TI  - The Proteus syndrome: CNS manifestations.
AB  - Proteus syndrome is a complex hamartomatous disorder characterized by multiple,
      diverse, somatic manifestations. We present a case in which severe, evolving CNS
      abnormalities were also exhibited. Imaging findings at presentation included
      hemimegalencephaly, subependymal calcified nodules, and periventricular cysts.
      Subsequently, dural sinus thrombosis developed. Eight previously reported
      patients may also have had hemimegalencephaly. When neuroimaging studies show
      hemimegalencephaly in a child with pigmented skin lesions, Proteus syndrome
      should be considered in the differential diagnosis.

PMID- 9613527
TI  - Functional magnetic resonance imaging: you get what you (barely) see.

PMID- 9613528
TI  - Developing tumor management for the developing brain.

PMID- 9613529
TI  - The role of CT angiography in the long-term management of cerebrovascular
      dissection.

PMID- 9613530
TI  - Thrombolytic treatment for acute stroke should be individualized for each
      patient.

PMID- 9613531
TI  - Spinal cord abnormalities in metabolic, nutritional, and toxic disorders.

PMID- 9613532
TI  - Peripheral nerve blocks--regional anesthesia for the new millennium.

PMID- 9613533
TI  - The practice of peripheral nerve blocks in the United States: a national survey
      [p2e comments].
AB  - BACKGROUND AND OBJECTIVES: A nationwide survey was conducted in order to describe
      practice patterns surrounding the use of peripheral nerve blocks (PNBs). METHODS:
      Questionnaires were mailed to 805 anesthesiologists selected systematically from
      the 1995 ASA and ASRA membership directories. Responses from 409 attending
      anesthesiologists (response rate 56.5%) were analyzed. RESULTS: While almost all
      respondents (97.8%) regularly use at least some regional anesthesia techniques in
      their practices, significantly fewer use PNBs, with most anesthesiologists
      (59.7%) performing less than five PNBs monthly. Peripheral nerve blocks of the
      lower extremity (femoral 32 %, sciatic 22 %, popliteal 11%) were less frequently
      used than PNB of the upper extremity (axillary 88%, interscalene 61%) (McNemar
      chi-square test = 215.2; P < .001). Anesthesiologists who rated their training in
      PNBs as adequate (50.8%) devoted a larger percentage of their practice to PNBs
      than anesthesiologists who rated their training as inadequate (P = .02). Despite
      the infrequent use of PNBs, 176 respondents (42.6%) predicted that their use of
      PNBs would increase in the future. CONCLUSIONS: Although this survey indicates
      that regional anesthesia is frequently practiced in the United States, PNBs and
      particularly PNBs of the lower extremities remain underutilized.

PMID- 9613534
TI  - Postoperative epidural injection of saline can shorten postanesthesia care unit
      time for knee arthroscopy patients.
AB  - BACKGROUND AND OBJECTIVES: The goal of this prospective, double-blind study was
      to ascertain if the postanesthesia care unit (PACU) stay of outpatients receiving
      epidural anesthesia for knee arthroscopy is decreased by injection of epidural
      saline at the end of the case. METHODS: Twenty healthy patients undergoing knee
      arthroscopy received lumbar epidural anesthesia with 2% lidocaine. At the end of
      surgery, in a double-blind design, group 1 patients (intervention group) received
      20 mL 0.9% saline injected into the epidural catheter. Patients in group 2
      (control group) had 1 mL 0.9% saline injected into the epidural catheter. In the
      PACU, the epidural catheter was removed, and motor block was assessed at 15
      minute intervals according to the Bromage scale. Standard discharge criteria for
      our ambulatory surgery center were followed. RESULTS: Patients who received 20 mL
      epidural 0.9% saline remained in phase I (intensive nursing) 83 +/- 8 minutes
      compared with control patients who stayed 110 +/- 8 minutes (P < .01). Nonmedical
      issues related to the unavailability of the patients transportation or waiting
      for medications to be issued from the pharmacy delayed discharge from phase II
      (non-nursing) in 70% of group 1 patients and 60% of group 2 patients. Time to
      actual hospital dismissal for group I was 119 +/- 14 minutes, compared with 159
      +/- 13 minutes (P < .05) for group 2. CONCLUSION: Patients receiving epidural
      anesthesia for knee arthroscopy had a shorter PACU stay if they received an
      injection of saline into the epidural space at the end of surgery.

PMID- 9613535
TI  - Intrathecal sufentanil (5 vs. 10 microg) for labor analgesia: efficacy and side
      effects.
AB  - BACKGROUND AND OBJECTIVES: Despite growing popularity, there are few studies
      examining the relative efficacy of different doses of intrathecal sufentanil for
      labor analgesia. This prospective, randomized, double-blind study compared the
      efficacy and side effects of 5 and 10 microg intrathecal sufentanil. METHODS:
      Sixty-three healthy, laboring, term parturients < or =5 cm cervical dilation
      participated in this study. In a randomized, double-blind fashion, patients
      received 5 or 10 microg intrathecal sufentanil as part of a combined spinal
      epidural technique. Patients rated pain, itching, nausea, and sedation on verbal
      analog scales before and every 10 minutes after drug injection. We also recorded
      maternal blood pressure and peripheral oxygen saturation before and every 10
      minutes after drug injection. Before and 30 and 60 minutes after drug injection,
      we measured maternal end-tidal CO2. RESULTS: Both doses of sufentanil provided
      adequate analgesia. Although 10 microg sufentanil produced slightly more profound
      analgesia, the duration of pain relief did not differ between the two groups.
      Both drug doses were associated with significant increases in itching and end
      tidal CO2. The 10-microg dose was associated with more sedation and a greater
      decrease in SaO2. CONCLUSIONS: Both 5 and 10 microg intrathecal sufentanil
      provided adequate labor analgesia. Both doses were associated with measurable
      spinal (itching) and supraspinal (sedation, respiratory depression) side effects.

PMID- 9613536
TI  - The rate of successful reactivation of labor epidural catheters for postpartum
      tubal ligation surgery.
AB  - BACKGROUND AND OBJECTIVES: Epidural catheters placed for analgesia during labor
      and delivery can be reused in the postpartum period for postpartum tubal ligation
      anesthesia. This study examined the success rate of such reactivation of epidural
      catheters. METHODS: We studied all patients who had received an epidural
      anesthetic for labor and delivery and who had the epidural catheter reactivated
      at a later time to provide anesthesia for a postpartum tubal ligation (PPTL)
      procedure between January, 1993 and June, 1995. The patients were divided into
      four groups based on the interval between delivery and PPTL incision: (a) less
      than 8 hours, (b) 8 hours to less than 16 hours, (c) 16 hours to less than 24
      hours and (d) 24 hours or more. RESULTS: Overall, 92% (129/140) of the patients
      had their epidural catheters successfully reactivated. The success rate in all
      but the last group was over 90%, while only 80% of catheters could be reactivated
      if left in place for more than 24 hours. CONCLUSIONS: Epidural catheters can be
      reactivated reliably for as long as 24 hours after they are placed.

PMID- 9613537
TI  - Computed tomographic study of lumbar (L3-4) epidural depth and its relationship
      to physical measurements in young adult men.
AB  - BACKGROUND AND OBJECTIVES: This study was performed to devise a method for
      predicting epidural depth more accurately with a variety of physical measurements
      not previously studied. METHODS: Computed tomography was used to accurately
      measure the L3-4 epidural depth. The inclusion criteria were restricted to
      healthy men, 20-25 years of age, in order to rule out the influences of age and
      sex. RESULTS: Significant correlations with depth from skin to the center of the
      "triangular" posterior epidural space (Sk-Ep) were found for waist circumference,
      waist circumference/height ratio, body mass index (BMI), weight/height ratio,
      weight/neck circumference ratio, and weight. The depth from the supraspinous
      ligament to the center of the posterior epidural space (SI-Ep) did not correlate
      with any physical measurements. However, Sk-Sl, which equals Sk-Ep minus Sl-Ep
      (ie, the depth from the skin to the supraspinous ligament) correlated with waist
      circumference/height ratio, waist circumference, BMI, and weight/height ratio.
      CONCLUSION: Addition of the physical parameters such as waist circumference/neck
      circumference ratio or BMI results in a higher predictive value for epidural
      depth than use of more traditional physical parameters such as weight/height
      ratio and/or weight only. The value of Sl-Ep is independent of any physical
      parameters. Thus, the significant correlation between the physical measurements
      and the epidural depth seems to be due only to obesity-related factors.

PMID- 9613538
TI  - The relative increase in skin temperature after stellate ganglion block is
      predictive of a complete sympathectomy of the hand.
AB  - BACKGROUND AND OBJECTIVES: Although an increase in skin temperature of the hand
      implies sympathetic block after stellate ganglion block (SGB), it does not
      indicate complete sympathetic block unless accompanied by an absence of sweating
      because skin temperature may increase even with a partial sympathetic block. This
      study examined the efficacy of the SGB to block sweating in the hand and to
      determine if the magnitude of temperature change in the hand is predictive of a
      negative sweat test. METHODS: Fifty-nine SGBs were performed in 30 patients (15
      women and 15 men) for diagnostic or therapeutic indications. Stellate ganglion
      block was performed via an anterior paratracheal approach at C6 using 15 mL 0.25%
      bupivacaine. Skin temperature was measured bilaterally on the index finger. A
      cobalt blue sweat test was performed bilaterally pre- and post-SGB on the middle
      finger. Successful sympathetic block after SGB was considered present when: (a)
      (change in ipsilateral temperature (postblock-preblock)] (Di)-[change in
      contralateral temperature] (Dc) > or = 1.5 degrees C; (b) Horner's syndrome
      present; and (c) sweat test changed from positive to negative. Logistical
      regression was applied to determine what value of Di - Dc could be used to
      predict a negative sweat test. RESULTS: Thirty-six percent (21/59) of blocks met
      all three criteria. Of the blocks where Di - Dc > or = 1.5 degrees C, 72% (21/29)
      had a negative sweat test post-SGB. Of the blocks where Di - Dc < 1.5 degrees C,
      37% (11/30) had a negative sweat test postblock. If Di - Dc > or = 2.0 degrees C,
      a negative sweat test could be predicted with 69 +/- 12% sensitivity and 85 +/-
      10% specificity. CONCLUSIONS: Stellate ganglion block often fails to increase
      skin temperature in the ipsilateral more than the contralateral hand. A value of
      Di - Dc > or = 2.0 degrees C was a good predictor of a sympathetic block, but was
      not sufficient to guarantee a complete sympathetic block of the hand after SGB in
      all cases. An apparently successful SGB as measured by "usual" clinical criteria
      may not result in a complete sympathectomy of the hand as is often assumed.
      Therefore, if obtaining a sympathectomy is important for diagnostic or
      therapeutic purposes, performing a sweat test provides important confirmatory
      evidence of the genuine success of the sympathetic block.

PMID- 9613540
TI  - Cholestasis as a side effect of bupivacaine?
AB  - BACKGROUND AND OBJECTIVES: Cholestasis has been proposed as a side effect of
      interpleural bupivacaine. Therefore, the effects of various application
      techniques on liver enzymes were studied following ethics committee approval and
      informed patient consent. METHODS: Patients following scheduled thoracotomy and
      laparoscopic cholecystectomy were prospectively studied and randomized to the
      following application techniques of bupivacaine: Thoracic surgery. T0: Control
      (systemic analgesia only: patient-controlled analgesia with opioids; n = 26); T1:
      Repetitive intercostal blocks (10-20 mL 0.5% bupivacaine, 2-4 times per day for 3
      6 days; n = 17); T2: Interpleural injections via a catheter placed
      intraoperatively (20 mL 0.25%, 4-6 times per day for 3-6 days, right: n = 25 or
      left: n = 12). Laparoscopic cholecystectomy. Intraperitoneal application (single
      injection). L0: 50 mL saline (Control) (n = 21). L1: 50 mL 0.125% bupivacaine (n
      = 18); L2: 50 mL 0.25% (n = 20). The serum concentrations of bilirubin, gamma-GT,
      alkaline phosphatase, leucine amino peptidase, glutamate oxalacetate
      transaminase, and glutamate pyruvate transaminase were measured preoperatively
      and on day 1, 3, and 7 postoperatively. RESULTS: Neither application of plain
      bupivacaine was associated with significant changes in the postoperative
      concentration of hepatic enzymes. In particular, there was no difference between
      left- and right-sided interpleural application. Although increases in hepatic
      enzyme concentrations were observed in some patients postoperatively, this was
      similar in the bupivacaine and control groups. CONCLUSION: Perioperative
      interpleural, intercostal, and intraperitoneal administration of bupivacaine was
      not associated with findings indicative of cholestasis in the early postoperative
      course.

PMID- 9613539
TI  - Comparison of double-hole and single-hole pencil-point needles for spinal
      anesthesia with hyperbaric bupivacaine.
AB  - BACKGROUND AND OBJECTIVES: The use of thin single-hole pencil-point (SHPP) spinal
      needles may be a reason for subarachnoid maldistribution of local anesthetic. A
      new double-hole pencil-point (DHPP) needle may be preferable because of a
      theoretic more uniform initial distribution of local anesthetic. METHODS: This
      was a prospective, double-blinded study of 50 patients randomly selected to have
      spinal anesthesia using either single-hole 27-gauge (B. Braun, Melsungen,
      Germany) or double-hole 26-gauge (A.L.B. Medical Inc., U.S.A.) pencil-point
      needles. The former were inserted with the side port directed caudally and the
      latter with openings in both caudal and cranial direction. Two milliliters of
      hyperbaric 0.5% bupivacaine were injected in 1 minute, and sensory and motor
      block were studied at regular intervals during spinal anesthesia. All patients
      were interviewed on the first (personal) and the seventh (mailed questionnaire)
      postoperative day. Furthermore, microscopic inspection of the spinal needles was
      performed. RESULTS: There were no statistically significant differences in
      sensory or motor block levels between the two needle types at any time during
      spinal anesthesia. Likewise, there was no difference in the duration of spinal
      block. The postanesthetic side effects (headache, backache, pricking, numbness,
      weakness) were similar in both groups. Light and electron microscopic examination
      showed resistance of the SHPP needles to tip damage. On the other hand, the DHPP
      needle tips seemed to be distorted quite frequently, and, even in unused needles,
      the tip was blunt and asymmetric. CONCLUSION: There was no difference between the
      spread of analgesia using either SHPP or DHPP spinal needles. The DHPP needles
      appear to be vulnerable to tip damage from mechanical contact.

PMID- 9613541
TI  - Intrathecal anesthesia with ketamine.
AB  - BACKGROUND AND OBJECTIVES: Intrathecal anesthesia is the method of choice for
      transurethral prostate resection in the United Kingdom, despite its associated
      hypotension. Intrathecal ketamine with epinephrine has been used for lower limb
      surgery with minimal cardiovascular disturbance. Because cardiovascular stability
      might be advantageous in this group of elderly patients, we undertook this study
      to determine if intrathecal ketamine was a suitable intrathecal anesthetic agent
      for transurethral prostate surgery. Because of the high incidence of side effects
      and inadequate analgesia, the study was terminated after only ten patients had
      been recruited. METHODS: Ten ASA I to III males were studied. Spinal anesthesia
      was performed with a 25-gauge Whitacre needle at the L2-L3 or L3-L4 space. The
      dose of ketamine was determined by a sequential allocation technique after
      initial empirical doses of 0.5 and 0.75 mg/kg. Sensory and motor block were
      monitored using pinprick and modified Bromage score, respectively. If spinal
      anesthesia was inadequate at any time, a general anesthetic was administered.
      RESULTS: At doses higher than 0.7 mg/kg, intrathecal ketamine produced both motor
      and sensory block. The onset of motor block was within 2-3 minutes, peaked in 5
      10 minutes, and lasted 30-60 minutes. Sensory block took 5-20 minutes to reach
      its maximal height. Maximum sensory block height varied from L1 to T7. Despite
      adequate block to pinprick, half the patients sensed the diathermy and were given
      a general anesthetic. The incidence of severe psychotomimetic side effects was
      30%. CONCLUSIONS: Intrathecal ketamine at doses of 0.7-0.95 mg/kg produces
      sensory and motor block. The frequency of psychomimetic disturbance, inadequate
      analgesia, and short duration of action preclude its use as a sole anesthetic
      agent.

PMID- 9613542
TI  - Mesmeric anesthesia: the case of Madam Plantin.

PMID- 9613543
TI  - Sympathetic nerve blocks: in search of a role.
AB  - OBJECTIVE: The role of sympathetic blocks in pain therapy is examined in the
      light of changing concepts of pain pathophysiology. A critical review of the
      literature also sought to develop an evidence-based analysis of outcome studies
      to provide recommendations for appropriate applications of sympathetic blocks,
      together with ideas for further clinically based research. METHODS: A focus on
      the pathophysiology of neuropathic and inflammatory pain disorders was used to
      help redefine what contribution, if any, was provided by the sympathetic system,
      to chronic pain states. Validation of nerve block therapies based on historical
      practices and these newer concepts and outcome determinations has then been used
      to present an overview of clinical nerve block therapies as applied to the
      sympathetic nervous system. RESULTS: 1. Pain Diagnosis: A reclassification of
      reflex sympathetic dystrophy (RSD) to the new taxonomy of complex regional pain
      syndromes (CRPS) is supported, with evidence that only a questionable sympathetic
      contribution at the dorsal root ganglion level can be ascribed etiologically to
      this group of disorders. Sympathetic blocks can establish whether pains may be
      nonresponsive or variably responsive to such blocks, but are considered
      inappropriate in determining a clinical diagnosis. 2. Neuropathic Pain Therapy:
      (a) A critical review of the literature regarding the use of sympathetic blocks
      in the treatment of acute herpes zoster pain and in the treatment of postherpetic
      neuralgia found little support for the widely held view that sympathetic blocks
      reduced either the incidence of long-term reduction of pain in these disorders.
      Further attempts to reduce PHN by the combination of blocks with aggressive drug
      therapies during acute herpes infection are suggested. (b) CRPS (RSD) treatments
      are seen as evolutionary at present, with the role of sympathetic blocks being
      only part of a balanced pain treatment strategy aimed at getting patients
      activated under cover of good analgesia and improved function. These proposals
      come as consensus recommendations but are not substantiated by outcome studies.
      3. Ischemic Pain: Permanent sympathetic block with neurolytic or
      thermocoagulation techniques provides up to 50% long-term improved blood flow and
      reduction of pain and ulceration for patients with advanced peripheral vascular
      disease. This is particularly appropriate at lumbar levels in which percutaneous
      techniques are safe when conducted with real time imaging control. CONCLUSIONS:
      Changes in the understanding of CRPS disorders and the role of the sympathetic
      nervous system in neuropathic pain has changed both the diagnostic and management
      strategies for these pain states. The sensitivity and specificity of response to
      sympathetic blocks in establishing their value at diagnostic aids will not be
      fully established without further clinical study. Further use of intravenous
      regional blocks or diagnostic intravenous infusions remains questionable.
      Preventive and therapeutic use of sympathetic blocks in herpes zoster pain
      remains open to well-controlled study.

PMID- 9613544
TI  - Paravertebral somatic nerve block for outpatient inguinal herniorrhaphy: an
      expanded case report of 22 patients.
AB  - BACKGROUND AND OBJECTIVES: Inguinal herniorrhaphy is a common outpatient surgical
      procedure. However, anesthetic techniques for inguinal herniorrhaphy are still
      associated with numerous side effects. Paravertebral somatic nerve block (PSNB)
      has the potential advantage to offer unilateral abdominal wall anesthesia and
      long-lasting pain relief with minimal side effects. We report our initial trial
      of PSNB for outpatient inguinal herniorrhaphy. METHODS: Twenty-two patients
      received a PSNB at T10 to L2 using 5 mL of 0.5% bupivacaine with epinephrine
      1:400,000 at each of the five levels. The onset of surgical anesthesia, duration
      of analgesia, side effects, and patient satisfaction with the technique were
      documented. RESULTS: Surgical anesthesia occurred 15-30 minutes after injection.
      Two patients had a failed block. The mean +/- SD time to onset of discomfort was
      14 +/- 11 hours. Time until first narcotic requirement was 22 +/- 18 hours.
      Thirteen patients (n = 20) had no incisional discomfort 10 hours or longer after
      their blocks. Three patients had epidural spread. Most patients were very
      satisfied with their anesthetic technique. CONCLUSIONS: The results of our
      initial experience suggest that PSNB is a potentially safe and effective
      technique. In general, the block provided long-lasting pain relief in most
      patients with few side effects. A randomized study comparing paravertebral blocks
      with conventional anesthesia choices is suggested given the findings in this
      initial series of patients.

PMID- 9613545
TI  - Sacral foraminal subarachnoid block: an expanded case report.
AB  - BACKGROUND AND OBJECTIVES: The sacral foraminal subarachnoid block is a method to
      access the subarachnoid space at the sacral level through the upper posterior
      sacral foramina. METHOD AND RESULTS: This expanded case report describes the use
      of this technique in 40 patients, ranging in age from 34 to 100 years. In 38
      patients, the sacral foraminal block was performed satisfactorily with adequate
      analgesia and without complications. In two patients, the technique was abandoned
      because of technical difficulties, and the block was done at the lumbar level.
      All the patients were monitored for up to 3 days after surgery with no
      complications noted. No postspinal headaches were observed. CONCLUSIONS: A sacral
      foraminal subarachnoid block is performed at the distal end of the dural sac.
      This technique is proposed as an alternative for a difficult lumbar or
      lumbosacral subarachnoid block.

PMID- 9613546
TI  - Six years of continuous intrathecal infusion of opioid and bupivacaine in the
      treatment of refractory pain due to intrapelvic extrusion of bone cement after
      total hip arthroplasty.
AB  - BACKGROUND AND OBJECTIVES: There is at present no reliable method for long-term
      treatment of severe pain following complications of total hip arthroplasty. We
      explored the long-term use of continuous intrathecal opioid/bupivacaine analgesia
      in a case not amendable to corrective surgery. METHODS: A 77-year-old woman,
      having a total hip arthroplasty, developed refractory nociceptive-neuropathic
      pain located at the ventral and dorsal aspects of the left hip. Radiographs
      showed a mandarine-sized intrapelvic mass of bone cement adhering to the roof of
      the acetabular cup. Further surgery had been declined by the surgeon and by the
      patient. An 18-gauge Portex intrathecal catheter was inserted, and an intrathecal
      infusion of 4.75 mg/mL bupivacaine and 0.015 mg/mL buprenorphine was started from
      a portable Pharmacia-Deltec (St. Paul, Minnesota) pump. RESULTS: The mean daily
      doses during the treatment period (more than 6 years up to now) were 37 mg for
      bupivacaine and 0.114 mg for buprenorphine. The intrathecal treatment gave the
      patient 85-100% pain relief. The patient could transport herself in a wheelchair,
      was able to perform her own hygiene, receive visits, read, watch television, and
      also shop and visit restaurants. There has been no need to replace the
      intrathecal catheter. CONCLUSION: Intrathecal infusion of opioid/bupivacaine can
      provide satisfactory long-term analgesia in patients with refractory pain from
      the hip joint.

PMID- 9613547
TI  - Patient-controlled analgesia using ropivacaine via an intrathecal catheter.
AB  - BACKGROUND AND OBJECTIVES: A 38-year-old woman presented with severe intractable
      pain in the sacral and perirectal areas secondary to metastatic stage I.B.
      squamous cell carcinoma of the cervix. METHODS: An indwelling epidural catheter
      was placed to control the patient's symptoms after failure of conservative
      therapies. Finally, an infusion containing isobaric 0.2% ropivacaine with 0.002%
      preservative-free morphine and 0.0002% epinephrine was started to treat her pain
      and preserve motor function to preserve quality of life. RESULTS: The patient
      obtained good pain relief with this regimen and was discharged home. She was able
      to walk with assistance and maintain good quality of life until her death
      approximately 7 weeks after the placement of the indwelling epidural catheter.
      CONCLUSION: The use of ropivacaine in combination with other analgesics, via an
      intrathecal catheter for patient-controlled analgesia, was an effective treatment
      for this patient. In the future, ropivacaine administered epidurally or
      intrathecally alone, or in combination with other analgesics, may become the
      local anesthetic of choice due to its preservation of motor function. Certainly,
      further scientific studies are indicated in the cancer patient population.

PMID- 9613548
TI  - Some misleadings about ketamine and their preservatives.

PMID- 9613549
TI  - Safety of epidural endoscopy.

PMID- 9613550
TI  - "Glucose test" by the blood sugar test machine.

PMID- 9613551
TI  - Pain relief after laparoscopic tubal ligation with local anesthetic injection
      into fallopian tubes.

PMID- 9613552
TI  - Doppler guidance for epidural catheter placement.

PMID- 9613553
TI  - A herpes zoster outbreak temporarily associated with an epidural steroid
      injection.

PMID- 9613554
TI  - Use of caudal morphine as preemptive analgesia prior to lumbar disc surgery.

PMID- 9613555
TI  - Regional increases in [11C]flumazenil binding after epilepsy surgery.
AB  - INTRODUCTION: Animal experiments suggest that epileptic seizures alter the
      expression of mRNA for neuro-receptors. PET measurements with [11C]flumazenil
      show that patients with partial seizures have a reduced density of benzodiazepine
      (BZ) receptors in the epileptogenic regions (ER) and some of the target areas for
      seizure activity, the so called projection areas. Recent data suggest that the
      degree of BZ receptor reduction in ER is correlated to seizure frequency. We
      therefore hypothesized that seizure activity can alter the BZ receptor binding,
      and that some of these changes could normalize when the seizures disappeared.
      METHODS: In 4 patients whose seizures were generated by mesial temporal lobe
      structures, BZ receptor density was measured with [11C]flumazenil PET before, and
      1 year after the epilepsy surgery and cessation of seizures. By use of a
      computerized anatomical brain atlas the same regions were analyzed in both PET
      scans, and the results related to data from 7 healthy controls. RESULTS:
      Presurgical PET scans showed reductions in BZ receptor density in the
      epileptogenic region and some of its primary projection areas. Other cortical
      regions had normal values. Postsurgically, the calculated BZ receptor density
      normalized (29+/-17% increase) in several of the affected projection areas,
      whereas the values in other cortical regions remained unaltered. CONCLUSION:
      Regional reductions in BZ receptor density may be dynamic and related to
      seizures. The present preliminary observations encourage further studies on
      seizure-related changes in regional receptor binding in humans.

PMID- 9613556
TI  - Impact of epilepsy on QOL in a Portuguese population: exploratory study.
AB  - OBJECTIVES: To develop an outcome measure of QOL (quality of life) for the
      Portuguese population; describe QOL in epileptics; analyse how QOL is affected by
      epilepsy and analyse how QOL is affected by patients' characteristics. PATIENTS
      AND METHODS: Study of a consecutive sample of 92 epileptics from an outpatient
      clinic, men and women, aged 15-65, having the basic education level. Firm
      diagnosis of epilepsy (with or without seizures) without other illness. A
      questionnaire based on ESI-55 and Health Insurance Experiment Short-Forms was
      used. Principal component analysis (orthogonal varimax) showed a solution
      explaining 55.6 of total variance. After the inspection, the 33 items were
      grouped into 5 sub-scales (dimensions). RESULTS: Results showed that QOL was poor
      for people with partial seizures. The best scores were found on patients now free
      from seizures. CONCLUSION: The QOL measure is sensitive to cultural differences,
      demographic and disease variables which could explain the results found.

PMID- 9613557
TI  - Low dosage clozapine effects on L-dopa induced dyskinesias in parkinsonian
      patients.
AB  - OBJECTIVES: The aim of this study was to investigate the clinical efficacy of
      clozapine, an atypical neuroleptic, on L-dopa induced dyskinesias of Parkinson's
      disease. MATERIAL AND METHODS: In an open study, a group of 10 PD patients was
      treated with low dosage clozapine (mean 30 mg/day) for a 4-month period and L
      dopa dyskinesias were evaluated in basal conditions and during clozapine
      treatment after the usual morning dose of clozapine. We utilized the AIMS for
      evaluation of dyskinesias and UPDRS for the assessment of motor performances.
      RESULTS: Clozapine produced a significant (P<0.05) reduction of dyskinesias 1
      week after the therapy onset. This effect was more pronounced at the end of the
      2nd week and remained stable through the following months. We did not observe
      significant variations of motor performances. CONCLUSION: A low dose of clozapine
      appears to be beneficial for patients with L-dopa induced dyskinesias that do not
      respond to other drugs and therapeutic measures.

PMID- 9613558
TI  - Glutamine synthetase activity in patients with Parkinson's disease.
AB  - According to current concepts, the excitatory amino acid glutamate is involved in
      the pathogenesis of Parkinson's disease (PD). Overactivity of glutamatergic
      projection neurons and beneficial effect of antiglutamatergic substances in
      animal experiments suggest that excess supply of glutamate might contribute to
      the pathophysiology of PD. Reduced activity of the glutamate metabolizing enzyme
      glutamine synthetase (GS) leads to decreased uptake of glutamate and thus
      abundant glutamate. Here we report that PD patients and age-matched controls are
      comparable with respect to GS activity in peripheral blood mononuclear cells
      (PBMC). These results imply no systemic dysregulation of the enzyme GS in
      patients with PD.

PMID- 9613559
TI  - Decreased myocardial 123I-MIBG uptake in Parkinson's disease.
AB  - We studied myocardial 123I-metaiodobenzylguanidine (MIBG) accumulation in 12
      patients with Parkinson's disease (PD). MIBG is an analog of norepinephrine (NE)
      and a tracer for sympathetic neuron integrity and function. MIBG uptake of the
      myocardium was significantly lower in PD than in controls. The heart to
      mediastinum ratio (H/M) was calculated by using the average count per pixel for
      the heart and mediastinum. In PD, H/M was lower than in controls (P<0.0001),
      while the washout ratio of the heart was higher (P<0.001). A decrease in
      myocardial accumulation of MIBG was observed in the early stage of PD. This
      suggests that the measurement of MIBG may help the diagnosis of early PD, and the
      causative factor underlying in PD may be operating the NE neuron as well as
      dopamine neuron.

PMID- 9613560
TI  - Impaired cardiac uptake of meta-[123I]iodobenzylguanidine in Parkinson's disease
      with autonomic failure.
AB  - OBJECTIVE: To selectively investigate postganglionic sympathetic cardiac neurons
      in patients with Parkinson's disease and autonomic failure. MATERIAL AND METHODS:
      Metaiodobenzylguanidine (MIBG) is a pharmacologically inactive analogue of
      noradrenaline, which is similarly metabolized in noradrenergic neurons. Therefore
      the uptake of radiolabelled MIBG represents not only the localization of
      postganglionic sympathetic neurons but also their functional integrity. Ten
      patients with Parkinson's disease and autonomic failure underwent standardized
      autonomic testing, assessment of catecholamine plasma levels and scintigraphy
      with [123I]MIBG. RESULTS: The cardiac uptake of MIBG, as demonstrated by the
      heart/mediastinum ratio, was significantly lower in patients in comparison with
      controls. Scintigraphy with MIBG allowed the selective in-vivo investigation of
      postganglionic sympathetic cardiac efferents in patients with autonomic failure,
      a procedure which was previously confined to post-mortem examination. CONCLUSION:
      These findings point to a relevant postganglionic pattern of involvement of the
      autonomic nervous system (ANS) in Parkinson's disease and autonomic failure.

PMID- 9613561
TI  - The prevalence of multiple sclerosis in the Hungarian city of Szeged.
AB  - OBJECTIVES: The aim of this study was to determine the prevalence of multiple
      sclerosis in a population in South Hungary. METHODS: The diagnosis was
      established with the aid of the Poser diagnostic criteria and the degree of
      physical disability was determined on the Kurtzke expanded disability status
      scale (EDSS). The present medical state (EDSS score) was determined from
      outpatient clinical control tests. The prevalence, the average age at onset of
      the disease and the proportions of the various clinical forms were calculated,
      and the patients' disability status was estimated. RESULTS: In 1996, the
      prevalence was 65/100,000, and the incidence from January 1, 1995 through
      December 31, 1996 was 7/100,000/year. DISCUSSION: During a period of 2 years, the
      number of diagnosed patients has almost doubled. The disease can be recognized in
      an early stage with a minimal neurological deficit. The development of the
      diagnostics necessitates re-examinations with modern diagnostic procedures.
      During the last 3 years, the general practitioner system has been reorganized,
      and the working relationships between the clinic and family doctors have
      developed considerably. A comparison of the present findings with those in other
      countries with a similar climate revealed very similar prevalence data.

PMID- 9613562
TI  - No evidence for increased frequency of autoantibodies during interferon-beta1b
      treatment of multiple sclerosis.
AB  - Interferon-beta1b (IFN-beta1b) is a widespread therapy of multiple sclerosis
      (MS), reducing the numbers and severity of exacerbations and the total lesion
      load measured by magnetic resonance imaging of the brain. Since IFN-beta1b has
      potent immunomodulatory properties, a potential side-effect of IFN-beta1b
      treatment could be the development of autoimmune responses. The frequencies of
      antinuclear and smooth muscle antibodies, antibodies against microsomal antigen
      of thyroid epithelial cells as well as a group of heterophilic antibodies were
      determined in 26 MS patients treated with IFN-beta1b for 3-20 months. No
      elevation of antibody titres was found for any of the antibodies studied when
      compared with paired samples obtained from most of the patients before the
      initiation of treatment. Although examined on a rather small group of patients,
      the results show no evidence of increased frequency of autoantibodies during
      interferon-beta1b treatment of multiple sclerosis.

PMID- 9613563
TI  - Sex-related differences in human cerebral hemodynamics.
AB  - OBJECTIVES: To identify possible inter-hemispheric sex-related cerebral
      hemodynamic differences at rest, in healthy subjects by transcranial Doppler
      (TCD). SUBJECTS AND METHODS: Mean flow velocity (MV) was recorded by TCD in 96
      (48 males, 48 females) right-handed volunteers. Mean age was similar in males and
      females, distribution of age-groups by sex was similar, too. RESULTS: Examining
      by sex MV values in each basal artery, left middle cerebral artery (MCA) showed a
      statistically significant difference (53.5+/-8.2 cm x s(-1) in males versus
      58.5+/-10.4 cm x s(-1) in females, P=0.005, one-way ANOVA). Multiple regression
      models show a significant correlation between age and MV on each side, while sex
      correlates with MV on the left side. CONCLUSION: A sex-dependent hemispheric
      difference in MV in the left MCA at rest (females>males) in the younger
      population subgroup was identified. These data support recent observations on
      anatomical differences between sexes, referring a proportionally larger Broca
      area in females compared to males.

PMID- 9613564
TI  - The effect of magnetic coil orientation on the excitation of the median nerve.
AB  - OBJECTIVE: We investigated the effect of magnetic coil orientation on the
      excitation of the median nerve in healthy subjects. METHODS: An 8-shaped coil,
      3.2 cm in outer diameter, was used. The median nerve was stimulated at the elbow
      while the compound muscle action potentials (CMAPs) of abductor pollicis brevis
      muscle were recorded at 4 different directions of the induced current:
      orthodromic, antidromic, medio-lateral and latero-medial. RESULTS: We found that
      the amplitude of the CMAP was the greatest in a medio-lateral (ML) direction. We
      also measured the induced electric field in the saline tank that mimicked the
      forearm. The induced electric field and its spatial gradient were the greatest in
      the ML direction among 4 directions. CONCLUSION: The fact that the forearm is a
      restrictive volume conductor may result in the different effects of coil
      orientation on the excitation of the median nerve at the elbow.

PMID- 9613565
TI  - Usefulness of MR angiography in detection of persistent trigeminal arteries.
AB  - OBJECTIVES: To examine the usefulness of magnetic resonance angiography (MRA) in
      detection of persistent trigeminal arteries (PTA). MATERIAL AND METHODS: 3D-time
      of-flight (TOF)-MRA images obtained from 1100 patients (798 males and 302 females
      aged 6-75 years with a mean of 55 years) at our and related institutions were
      examined retrospectively for PTA. The course of the PTA was classified into the
      posteromedial type and posterolateral type. Charts of the patients were also
      examined retrospectively for clinical symptoms related to PTA. RESULTS: PTA was
      observed in 5 (0.45%) of the 1100 patients, and no aneurysm or arteriovenous
      malformation was noted in any of these 5 patients. PTA was the posteromedial type
      in 2 and posterolateral type in 3. PTA was possibly related with clinical
      symptoms in only 1 patient with oculomotor paresis. CONCLUSION: MRA is useful for
      non-invasive screening for PTA.

PMID- 9613566
TI  - Analysis of an abscisic acid (ABA)-responsive gene promoter belonging to the Asr
      gene family from tomato in homologous and heterologous systems.
AB  - Asr is a family of genes that maps to chromosome 4 of tomato. Asr2, a recently
      reported member of this family, is believed to be regulated by abscisic acid
      (ABA), stress and ripening. A genomic Asr2 clone has been fully sequenced, and
      candidate upstream regulatory elements have been identified. To prove that the
      promoter region is functional in vivo, we fused it upstream of the beta
      glucuronidase (GUS) reporter gene. The resulting chimeric gene fusion was used
      for transient expression assays in papaya embryogenic calli and leaves. In
      addition, the same construct was used to produce transgenic tomato, papaya,
      tobacco, and potato plants. Asr2 upstream sequences showed promoter function in
      all of these systems. Under the experimental conditions tested, ABA stimulated
      GUS expression in papaya and tobacco, but not in tomato and potato systems.

PMID- 9613567
TI  - RNA processing is involved in the post-transcriptional control of the citQRP
      operon from Lactococcus lactis biovar diacetylactis.
AB  - The importance of Lactococcus lactis biovar diacetylactis (L. diacetylactis) in
      the dairy industry is due to its ability to produce aroma compounds, such as
      acetoin and diacetyl, from citrate. The first step in citrate utilization is its
      uptake by the cells. In L. diacetylactis, the citrate transport system is encoded
      by the citQRP operon. We have previously proposed that expression of citQRP
      operon is regulated at the post-transcriptional level. In this paper, we show
      that the cit mRNA is processed at a complex secondary structure in L.
      diacetylactis and Escherichia coli. This secondary structure includes the 5'
      terminal two-thirds of citQ and the overlap between citQ and citR. Primer
      extension analysis revealed that the major cleavage sites are located upstream of
      citR and within citQ. In an attempt to identify the enzyme(s) responsible for
      this cleavage, we have analyzed this processing in E. coli mutants deficient in
      endoribonucleases. A comparative analysis of cit mRNA degradation was performed
      in RNase E and RNase III mutants and in wild-type strains using Northern blot
      hybridization. This analysis revealed that the cit transcript is degraded into
      several breakdown products, which are significantly stabilized in the mutant
      lacking RNase III. Our results indicate that the complex secondary structure has
      a critical role in the control of the expression of cit mRNA. A model for
      processing is discussed.

PMID- 9613568
TI  - Effects of mutations in the Saccharomyces cerevisiae RNA14 gene on the abundance
      and polyadenylation of its transcripts.
AB  - In the yeast Saccharomyces cerevisiae, the RNA14 and RNA15 gene products have
      been implicated in RNA cleavage and polyadenylation in vitro and in the choice of
      polyadenylation site of ACT1 mRNA in vivo. The RNA14 gene produces three
      transcripts that differ in their 3' end, suggesting the use of different
      polyadenylation sites. The appearance of the three RNA14 transcripts was examined
      in different rna14 and/or rna15 mutant strains. In the rna14-1 or rna15-2 mutant
      strains, only the large transcript is present at the non-permissive temperature,
      showing that the rna14-1 and rna15-2 mutations lead to the use of the most distal
      RNA14 polyadenylation site, which turns out to be the most efficient. The rna14-5
      mutation, which does not primarily modify the choice of poly(A) site, increases
      the global amount of RNA14 transcript. Surprisingly, this RNA14 mRNA
      overproduction is also observed in the double rna14-1 rna15-2 mutant strain.
      Moreover, in the strains in which the RNA14 transcripts are overproduced, short
      heterogeneous polyadenylated antisense RNAs are detected in the 3' region of the
      RNA14 large transcript. Taken together these observations suggest that, in
      addition to poly(A) site choice, Rna14 protein has another function involved in
      the control of global RNA14 mRNA level.

PMID- 9613569
TI  - Cloning and characterisation of the pknD gene encoding an eukaryotic-type protein
      kinase in the cyanobacterium Anabaena sp. PCC7120.
AB  - Protein phosphorylation catalysed by protein kinases is an important mechanism
      for signal transduction in both prokaryotes and eukaryotes. A novel gene, pknD,
      encoding a protein similar to eukaryotic-type protein kinases, was cloned from
      Anabaena sp. PCC7120. The N-terminal region of PknD is 60% identical to that of
      PknA, another putative Ser/Thr kinase from the same strain. Both PknA and PknD
      have C-terminal regions that are rich in Pro and Thr residues. Expression of pknD
      was undetectable by RNA/DNA hybridisation and was thus examined by RT-PCR. The
      pknD transcript was detected in filaments cultured in the presence of either
      nitrate or ammonium as a source of combined nitrogen, and also in filaments
      transferred from nitrate-sufficient to N2-fixing conditions. pknD mutants were
      created, and their growth characteristics under different nitrogen regimes and
      their capacity for heterocyst development were investigated. The growth rates of
      the mutants were similar to those of the wild-type strain in the presence of
      either nitrate or ammonium, but were only 20% that of the wild type under N2
      fixing conditions. The rate of nitrogenase activity is normal in pknD mutant
      under aerobic conditions. Under nitrogen-fixing conditions, the inactivation of
      pknD led to enhanced modification of the PII protein compared to the weak
      phosphorylation of PII observed in the wild-type strain. This high level of PII
      phosphorylation in the pknD mutant is reminiscent of the situation in nitrogen
      starved Synechococcus PCC7942 cells. PknD might be involved in regulating
      nitrogen metabolism or nitrogen trafficking from heterocysts to vegetative cells.

PMID- 9613570
TI  - Cloning and characterisation of the Neisseria gonorrhoeae aroB gene.
AB  - The gene coding for the 3-dehydroquinate synthetase (aroB) of Neisseria
      gonorrhoeae has been cloned by functional complementation of an Escherichia coli
      aroB mutant. The aroB gene isolated from a gonococcal plasmid library encodes a
      359 amino acid protein with a molecular mass of 38.6 kDa. Alignment of different
      prokaryotic and eukaryotic aroB gene products reveals an overall identity ranging
      from 33 to 55%. An open reading frame coding for an aroK homologue is located
      immediately upstream of aroB. Downstream of aroB a region of inverted repeats and
      a gene showing high homology to yafJ of E. coli has been identified. Disruption
      of aroB generates a gonococcal mutant that is unable to grow in the absence of
      aromatic compounds. Complementation of the mutant with the intact aroB gene in
      trans indicates that the gene is responsible for the auxotrophic phenotype. In
      infection assays with AroB-deficient gonococcal strains, binding, entry and short
      term survival in epithelial cells is not affected. The aroB gene might be useful
      as a selectable marker and target for attenuation of a gonococcal live vaccine
      strain or as a biosafe laboratory strain.

PMID- 9613571
TI  - Genomic organization of the segment polarity gene pan in Drosophila melanogaster.
AB  - We previously described the molecular cloning of a mammalian T cell factor 1 (TCF
      1)-like protein from Drosophila melanogaster, encoded by the pangolin (pan)
      locus, and demonstrated that it consists of a DNA binding domain similar to that
      of other high mobility group proteins and a protein-protein interaction domain
      that binds beta-catenin (Armadillo in Drosophila) but that it lacks a
      transcriptional activation domain. Here we show that the pan locus spans
      approximately 50 kb and the mRNA results from the splicing of 13 exons. We note
      remarkable conservation of the exon/intron boundaries between the human and D.
      melanogaster genes, suggesting that they share a common ancestor. Chromosomal in
      situ hybridization locates pan to the base of chromosome 4, near the cubitus
      interruptus locus. Restriction map and sequence analyses confirm their close
      proximity. The small fourth chromosome undergoes little or no recombination and
      was previously reported to lack DNA polymorphisms; however, we note two DNA
      polymorphisms occurring in three combinations within the pan locus, demonstrating
      the presence of synonymous substitutions and the past occurrence of
      recombination. We present evidence suggesting that the protein encoded by pan is
      more similar to mammalian TCF-1 and Caenorhabditis elegans POP-1 than to
      mammalian LEF-1.

PMID- 9613572
TI  - Screening for glycosylphosphatidylinositol (GPI)-dependent cell wall proteins in
      Saccharomyces cerevisiae.
AB  - Open reading frames in the genome of Saccharomyces cerevisiae were screened for
      potential glycosylphosphatidylinositol (GPI)-attached proteins. The
      identification of putative GPI-attached proteins was based on three criteria: the
      presence of a GPI-attachment signal sequence, a signal sequence for secretion and
      a serine- or threonine-rich sequence. In all, 53 ORFs met these three criteria
      and 38 were further analyzed as follows. The sequence encoding the 40 C-terminal
      amino acids of each was fused with the structural gene for a reporter protein
      consisting of a secretion signal, alpha-galactosidase and a hemagglutinin (HA)
      epitope, and examined for the ability to become incorporated into the cell wall.
      On this basis, 14 of fusion proteins were classified as GPI-dependent cell wall
      proteins because cells expressing these fusion proteins: (i) had high levels of
      alpha-galactosidase activity on their surface; (ii) released significant amounts
      of the fusion proteins from the membrane on treatment with phosphatidylinositol
      specific phospholipase C (PI-PLC); and (iii) released fusion proteins from the
      cell wall following treatment with laminarinase. Of the 14 identified putative
      GPI-dependent cell wall proteins, 12 had novel ORFs adjacent to their GPI
      attachment signal sequence. Amino acid sequence alignment of the C-terminal
      sequences of the 12 ORFs, together with those of known cell wall proteins,
      reveals some sequence similarities among them.

PMID- 9613573
TI  - The novel function of the Saccharomyces cerevisiae CBP2 gene as a splicing factor
      essential to excision of the Saccharomyces douglasii LSU intron in vivo.
AB  - In the yeast Saccharomyces cerevisiae, the product of the nuclear gene CBP2 is
      required exclusively for the splicing of the terminal intron of the mitochondrial
      cytochrome b gene. The homologous gene from the related yeast, Saccharomyces
      douglasii, has been shown to be essential for respiratory growth in the presence
      of a wild-type S. douglasii mitochondrial genome and dispensable in the presence
      of an intronless mitochondrial genome. The two CBP2 genes are functionally
      interchangeable although the target intron of the S. cerevisiae CBP2 gene is
      absent from the S. douglasii mitochondrial genome. To determine the function of
      the CBP2 gene in S. douglasii mitochondrial pre-RNA processing we have
      constructed and analyzed interspecific hybrid strains between the nuclear genome
      of S. cerevisiae carrying an inactive CBP2 gene and S. douglasii mitochondrial
      genomes with different intron contents. We have demonstrated that inactivation of
      the S. cerevisiae CBP2 gene affects the maturation of the S. douglasii LSU pre
      RNA, leading to a respiratory-deficient phenotype in the hybrid strains. We have
      shown that the CBP2 gene is essential for excision of the S. douglasii LSU intron
      in vivo and that the gene is dispensable when this intron is deleted or replaced
      by the S. cerevisiae LSU intron.

PMID- 9613574
TI  - The O6-methylguanine-DNA methyltransferase from the hyperthermophilic archaeon
      Pyrococcus sp. KOD1: a thermostable repair enzyme.
AB  - The enzyme O6-methylguanine-DNA methyltransferase (MGMT) is the most common form
      of cellular defense against the biological effects of O6-methylguanine (O6-MeG)
      in DNA. Based on PCR amplification using primers derived from conserved amino
      acid sequences of MGMTs from 11 species, we isolated the DNA region coding for
      MGMT from the hyperthermophilic archaeon Pyrococcus sp. KOD1. The MGMT gene from
      KOD1 (mgtk) comprises 522 nucleotides, encoding 174 amino acid residues; its
      product shows considerable similarity to the corresponding mammalian, yeast and
      bacterial enzymes, especially around putative methyl acceptor sites. Phylogenetic
      analysis of MGMTs showed that archaeal MGMTs were grouped with their bacterial
      counterparts. The location of the MGMT gene on the KOD1 chromosome was also
      determined. The cloned KOD1 MGMT gene was overexpressed using the T7 RNA
      polymerase expression system, and the recombinant protein was purified by
      ammonium sulfate fractionation, heat treatment, ion-exchange chromatography and
      gel filtration chromatography. The purified recombinant protein was assayed for
      its enzyme activity by monitoring transfer of [3H]methyl groups from the
      substrate DNA to the MGMT protein; the activity was found to be stable at 90
      degrees C for at least 30 min. When the mgtk gene was placed under the control of
      the lac promoter and expressed in the methyltransferase-deficient Escherichia
      coli strain KT233 (delta ada, delta ogt) cells, a MGMT was produced. The enzyme
      was functional in vivo and complemented the mutant phenotype, making the cells
      resistant to the cytotoxic properties of the alkylating agent N-methyl-N'-nitro-N
      nitrosoguanidine.

PMID- 9613575
TI  - Analysis of eryBI, eryBIII and eryBVII from the erythromycin biosynthetic gene
      cluster in Saccharopolyspora erythraea.
AB  - The gene cluster (ery) governing the biosynthesis of the macrolide antibiotic
      erythromycin A by Saccharopolyspora erythraea contains, in addition to the eryA
      genes encoding the polyketide synthase, two regions containing genes for later
      steps in the pathway. The region 5' of eryA that lies between the known genes
      ermE (encoding the erythromycin resistance methyltransferase) and eryBIII
      (encoding a putative S-adenosylmethionine-dependent methyltransferase), and that
      contains the gene eryBI (orf2), has now been sequenced. The inferred product of
      the eryBI gene shows striking sequence similarity to authentic beta-glucosidases.
      Specific mutants were created in eryBI, and the resulting strains were found to
      synthesise erythromycin A, showing that this gene, despite its position in the
      biosynthetic gene cluster, is not essential for erythromycin biosynthesis. A
      mutant in eryBIII and a double mutant in eryBI and eryBIII were obtained and the
      analysis of novel erythromycins produced by these strains confirmed the proposed
      function of EryBIII as a C-methyltransferase. Also, a chromosomal mutant was
      constructed for the previously sequenced ORF19 and shown to accumulate
      erythronolide B, as expected for an eryB mutant and consistent with its proposed
      role as an epimerase in dTDP-mycarose biosynthesis.

PMID- 9613576
TI  - Increased transformation frequency and tagging of developmental genes in
      Aspergillus nidulans by restriction enzyme-mediated integration (REMI).
AB  - We have used a plasmid containing the argB gene to transform an Aspergillus
      nidulans argB-deleted strain in the presence of restriction enzymes and show a 20
      to 60-fold increase in transformation frequency via restriction enzyme-mediated
      integration (REMI). This procedure was used to try to tag new genes involved in
      the asexual development of this fungus. More than 2000 transformants isolated
      following electroporation of conidia and approximately 3700 transformants
      recovered following protoplast fusion were screened for sporulation defects.
      Unexpectedly, developmental mutants were obtained only when the protoplast fusion
      approach was used. Southern blot analysis of these mutants, and of randomly
      selected transformants obtained by electroporation, was consistent with the
      occurrence of single plasmid integration events in 33 and 65% of the cases,
      respectively. The argB marker was shown to be tightly linked to the mutant
      phenotype in only 62% of the mutants analyzed by sexual crosses. Partial DNA
      sequencing of a tagged gene, whose mutation delays asexual sporulation and
      results in a fluffy phenotype, showed no homology to previously reported
      sequences. Our results indicate that REMI can be used in A. nidulans to increase
      the transformation frequency and illustrate the advantages and potential problems
      when using REMI to tag genes of interest in this and other fungi.

PMID- 9613577
TI  - Datin, a yeast poly(dA:dT)-binding protein, behaves as an activator of the wild
      type ILV1 promoter and interacts synergistically with Reb1p.
AB  - A cis-acting element required for GCN4-independent basal-level transcription of
      ILV1 was previously identified in our laboratories as a binding site for the REB1
      protein (Reb1p). Further deletion analysis of the ILV1 promoter region identified
      a second element also required for GCN4-independent basal-level ILV1 expression.
      This second element is an A.T-rich tract (26 As out of 32 nucleotides) situated
      15 bp downstream of the Reb1p-binding site. Deletion of both the Reblp site and
      the poly(dA:dT) element totally eliminates basal activity of the ILV1 promoter.
      We show that the two elements act synergistically to control ILV1 expression and
      that the synergistic effect is distance dependent. We demonstrate that (i) datin
      (Dat1p), the only known poly (dA:dT)-binding protein in yeast, specifically binds
      to the ILV1 poly(dA:dT) element in vitro; (ii) Dat1p functions as a trans
      activating factor in the ILV1 context; and (iii) the synergistic activation
      observed in vivo between the Reb1p site and the poly(dA:dT) element depends on
      the presence of the structural gene for Dat1p, DAT1.

PMID- 9613578
TI  - The Cdc14 phosphatase is functionally associated with the Dbf2 protein kinase in
      Saccharomyces cerevisiae.
AB  - The Saccharomyces cerevisiae Cdc14 protein phosphatase and Dbf2 protein kinase
      have been implicated to act during late M phase, but their functions are not
      known. We report here that CDC14 is a low-copy suppressor of the dbf2-2 mutation
      at 37 degrees C. The kinase activity of Dbf2 accumulated at a high level, in
      vivo, during a cdc14 arrest and was also much higher in cdc14 mutant cells at the
      permissive temperature of growth, therefore in cycling mutant cells than in
      cycling wild-type cells. This correlated with the accumulation of the more slowly
      migrating form of Dbf2, previously shown to correspond to the hyperphosphorylated
      form of the protein. The finding that the dbf2-2 mutation could be rescued
      following overproduction of catalytically inactive forms of Cdc14 suggested that
      the control of Dbf2 activity by Cdc14 might be only indirect and independent of
      Cdc14 phosphatase activity. However, it was found that Cdc14 could form oligomers
      within the cell, thus leaving open the possibility that catalytically inactive
      Cdc14 might associate with wild-type Cdc14 and rescue dbf2-2 in a phosphatase
      dependent manner. We confirmed that overexpression of CDC14 could rescue
      mutations in CDC15, which encodes another kinase also implicated to act in late M
      phase. Cells of a cdc15-2 dbf2-2 double mutant died at temperatures much lower
      than did either single mutant, whereas there was only a slight additive phenotype
      in the cdc14-1 dbf2-2 and cdc14-1 cdc15-2 double mutant cells. Finally,
      functional association between Cdc14 and Dbf2 (and also Cdc15) was confirmed by
      the finding that the cdc14, dbf2 and cdc15 mutations could be partially rescued
      by the addition of 1.2 M sorbitol to the culture medium. Our data are the first
      to demonstrate a functional link between Cdc14 and Dbf2 based on both biochemical
      and genetic information.

PMID- 9613579
TI  - Identification of two processed psuedogenes of the human Tom20 gene.
AB  - The open reading frame (ORF) of the human Tom20 gene (hTom20) was amplified by
      PCR from a HeLa cDNA library using primers based on the sequence of HUMRSC145 and
      cloned into a pET15b vector. Amplification of human genomic DNA using these
      primers yielded a DNA fragment of the same size as that of the ORF of hTom20
      cDNA. Sequencing of this fragment revealed that: (1) it has the same number of
      base pairs as the ORF of hTom20 cDNA (438 bp); and (2) the two sequences differ
      by 14 single base pair substitutions (97% similarity) causing eight changes in
      the amino acid sequence and two premature stop codons. Further amplification of
      human genomic DNA adaptor-ligated libraries using primers based on HUMRSC145
      revealed three different sequence-related genomic regions; one corresponding to
      the fragment referred above, another corresponding to the hTom20 gene, and a
      third fragment of which the sequence differs from the ORF of hTom20 cDNA by only
      22 base pair substitutions and a deletion of 4 bp. We conclude that, in addition
      to the hTom20 gene, there are two genomic DNA sequences (psi1Tom20 and psi2Tom20)
      that are processed pseudogenes of hTom20. Aspects concerning their evolutionary
      origin are discussed.

PMID- 9613580
TI  - Use of the ARG7 gene as an insertional mutagen to clone PHON24, a gene required
      for derepressible neutral phosphatase activity in Chlamydomonas reinhardtii.
AB  - In Chlamydomonas reinhardtii, transforming DNA apparently integrates at random
      locations in the nuclear genome and generates a high number of mutants by gene
      inactivation. Twenty-four phoN mutants lacking the derepressible neutral (DN)
      phosphatase activity were isolated following transformation of the cw15arg7
      strain with plasmid pASL harbouring the ARG7 gene encoding argininosuccinate
      lyase. In all mutants resulting from the transformation with linearised pASL, a
      functional ARG7 copy was found to be closely linked to a phoN mutation but
      additional ARG7 copies were present elsewhere in the genome. Of the 13 mutants
      submitted to allelism analysis, four were allelic or tightly linked to the
      previously isolated MNNG-induced phoN mutants (phoN2, phoN3, phoN24), the
      remaining mutants were distributed among seven additional loci. To learn more
      about the function of the genes involved in DN phosphatase production, we cloned
      PHON24 by plasmid rescue and screening of a wild-type genomic library. One clone
      complemented the phoN24 mutation in cotransformation experiments, as did several
      subcloned fragments. In all phoN24+ transformants, the DN phosphatase activity
      was 2-3 times lower than in the wild-type strain but about 10 times higher than
      in the untransformed control. In wild-type, PHON24 transcript accumulation was
      independent of inorganic phosphate deficiency. The transcripts were present in
      the MNNG-induced phoN24 mutant but were lacking in the two insertional phoN24
      mutants. Insertional mutagenesis has thus permitted the isolation of novel
      mutants which were missing after induction with a chemical mutagen and the
      cloning of a gene which is probably involved in the regulation of the DN
      phosphatase.

PMID- 9613581
TI  - Refined genetic map of the obligate methylotroph Methylobacillus flagellatum.
AB  - We present a refined genetic map of the obligate methylotroph Methylobacillus
      flagellatum. New, Hfr (high-frequency-of-transfer) donors, and pulsed-field gel
      electrophoresis, were used to determine that M. flagellatum contains one
      approximately 3.1-Mb circular chromosome, and no plasmids. A correlation between
      time-of-entry units and DNA length was established. Using in vivo and in vitro
      cloning, and sequencing, a number of new genetic markers were identified and
      mapped; in addition, the nature of some of the previously mapped markers was
      elucidated.

PMID- 9613582
TI  - Phosphoinositide-specific phospholipase C forms a complex with 14-3-3 proteins
      and is involved in expression of UV resistance in fission yeast.
AB  - The fission yeast plc1+ gene encodes phosphoinositide-specific phospholipase C.
      The two- hybrid interaction assay with plexA-plc1+ as a bait revealed that Plc1p
      interacted with the 14-3-3 proteins Rad24p and Rad25p. Formation of a complex
      containing Plc1p and Rad24p in vivo was confirmed by an immunological method. As
      predicted from the fact that rad24 null mutant cells are hypersensitive to UV
      irradiation, plc1 null mutant cells were almost as sensitive to UV irradiation as
      rad24 null mutant cells. In addition, deletion of rad24 in the plc1 null mutant
      cells did not enhance the UV sensitivity, indicating that plc1+ and rad24+ belong
      to the same epistasis group with respect to UV sensitivity. Whereas Rad24p has
      been reported to be involved in the DNA damage checkpoint pathway, the delay to
      mitosis after UV irradiation was not defective either in rad24 null mutant cells
      or in plcl null mutant cells in our analysis. Thus, Plc1p is responsible for
      resistance to UV irradiation, but not for the DNA damage checkpoint pathway, in
      cooperation with 14-3-3 proteins.

PMID- 9613583
TI  - A screen for upstream components of the yeast protein kinase C signal
      transduction pathway identifies the product of the SLG1 gene.
AB  - We employed the constitutive BCK1-20 allele of the gene for the MAP kinase kinase
      kinase (MAP-KKK) in the yeast Pkc signal transduction pathway to develop a
      genetic screen for mutants in genes encoding upstream components. Transposon
      mutagenesis yielded a mutant that was completely dependent on the active allele
      in the absence of osmotic stabilization. The transposon had integrated at the
      yeast SLG1 (HCS77) locus. This gene encodes a putative membrane protein. Haploid
      slg1 deletion strains are sensitive to caffeine, as expected for mutants in the
      Pkc pathway, as well as a variety of other drugs. The response to elevated
      temperatures and the dependence on osmotic stabilization depends on the genetic
      background. Thus, in the strain used for mutagenesis, disruption of SLG1 causes
      the cells to become non-viable in the absence of osmotic stabilization at both 30
      degrees C and 37 degrees C. In a different genetic background this phenotype was
      not observed. Sensitivity of the haploid deletion mutants to caffeine can be
      partially suppressed by overexpression of genes for other components of the Pkc
      pathway, such as PKC1, SLT2, ROM2, and STE20. In addition, a SLG1-lacZ reporter
      construct shows higher expression in the presence of caffeine or magnesium
      chloride in a wild-type diploid background.

PMID- 9613584
TI  - Transport activity of FhuA, FhuC, FhuD, and FhuB derivatives in a system free of
      polar effects, and stoichiometry of components involved in ferrichrome uptake.
AB  - The Escherichia coli fhu operon, composed of the fhuA, C, D, and B genes, is
      essential for the utilization of ferric siderophores of the hydroxamate type and
      for the uptake of the antibiotic albomycin. We have had difficulty studying the
      effects of missense mutations in individual plasmid-encoded transport genes
      because appropriate test strains were not found: all isolated chromosomal
      mutations in either one of the fhu genes (with a complete loss of function)
      negatively influenced the expression of other fhu genes in the operon. In order
      to analyze Fhu mutant proteins in a system free of polar effects, we constructed
      a plasmid-encoded gene cassette system by introducing unique restriction sites
      that allowed precise cloning of individual fhu genes. The fhu cassette operon
      expressed in a chromosomal fhu deletion mutant enabled us to evaluate the
      transport activity of mutated FhuA, FhuC, FhuD or FhuB derivatives. In addition,
      we found that transport across the outer membrane (via FhuA, TonB, ExbB, D)
      rather than transport across the cytoplasmic membrane (via FhuC, D, B) was rate
      limiting. The stoichiometry of the components involved in the uptake of iron(III)
      hydroxamates seems to be important for proper functioning.

PMID- 9613585
TI  - Mutagenesis of the genes encoding subunits A, C, H, I, J and K of the plastid
      NAD(P)H-plastoquinone-oxidoreductase in tobacco by polyethylene glycol-mediated
      plastome transformation.
AB  - Plastids contain a NAD(P)H-plastoquinone-oxidoreductase (NDH complex) which is
      homologous to the eubacterial and mitochondrial NADH-ubiquinone-oxidoreductase
      (complex I), but the metabolic function of the enzyme is unknown. The enzyme
      consists of at least eleven subunits (A-K), which are all encoded on the plastid
      chromosome. We have mutagenized ndhC and ndhJ by insertion, and ndhK and ndhA-I
      by deletion and insertion, of a cassette which carried a spectinomycin resistance
      gene as a marker. The transformation was carried out by the polyethylene glycol
      mediated plastid transformation method. Southern analysis revealed that even
      after repeated regeneration cycles each of the four different types of
      transformants had retained 1-5% of wild-type gene copies. This suggests that
      complete deletion of ndh genes is not compatible with viability. The
      transformants displayed two characteristic phenotypes: (i) they lack the rapid
      rise in chlorophyll fluorescence in the dark after illumination with actinic
      light for 5 min; in the wild-type this dark-rise reflects a transient reduction
      of the plastoquinone pool by reduction equivalents generated in the stroma; and
      (ii) transformants with defects in the ndhC-K-J operon accumulate starch,
      indicating inefficient oxidation of glucose via glycolysis and the oxidative
      pentose phosphate pathway. Both observations support the theory of
      chlororespiration, which postulates that the NDH complex acts as a valve to
      remove excess reduction equivalents in the chloroplast.

PMID- 9613586
TI  - Integration host factor positively regulates cycJIH transcription.
AB  - We report the identification of integration host factor (IHF) as an additional
      element involved in the regulation of the cysJIH promoter of Salmonella
      typhimurium and Escherichia coli. An IHF-binding site was located in the
      regulatory region of the cysJIH promoter by using two methods, protection against
      DNase I digestion and hydroxyl radical cleavage. The positive influence of IHF on
      in vitro run-off transcription from the cysJIH promoter is shown. The in vivo
      observations suggest that IHF is necessary for full expression of cysJIH in
      stationary phase but not during exponential growth.

PMID- 9613587
TI  - Directed formation of chromosomal deletions in Salmonella typhimurium: targeting
      of specific genes induced during infection.
AB  - In vivo expression technology (IVET) has resulted in the isolation of more than
      100 Salmonella typhimurium genes that are induced during infection. Many of these
      in vivo induced (ivi) genes, as well as other virulence genes, are clustered in
      regions of the chromosome that are specific for Salmonella and are not present in
      Escherichia coli (e.g., pathogenicity islands). It would be desirable to be able
      to delete such putative virulence regions of the chromosome, and if the deletion
      removes genes that play a role in pathogenesis subsequent efforts can then be
      focused on individual genes that reside within that region. We therefore have
      developed a strategy for constructing chromosomal deletions which are not limited
      in size, have defined endpoints with a selectable marker at the joint point, and
      are not dependent on prior knowledge of sequences contained within the deleted
      region. Such deletion strategies can be applied to almost any bacterium with
      homologous recombination and to plasmid-based mutational systems where homologous
      recombination is not desired or feasible.

PMID- 9613588
TI  - Covalent complex of phenylalanyl-tRNA synthetase with 4-thiouridine-substituted
      tRNA(Phe) gene transcript retains aminoacylation activity.
AB  - s4U-containing transcripts of tRNA(Phe) gene have been prepared by complete
      substitution of 16 U residues or by random incorporation of s4U residues followed
      by affinity electrophoresis isolation of s4U-monosubstituted tRNA transcripts.
      Both analogs have been cross-linked to Thermus thermophilus phenylalanyl-tRNA
      synthetase (PheRS) and the specificity of the cross-linking has been
      demonstrated. Functional activity of the covalent complex of PheRS with the s4U
      monosubstituted transcript has been shown by aminoacylation of 60% of the enzyme
      cross-linked tRNA. This is the first instance in which biological activity of
      aminoacyl-tRNA synthetase and cross-linked tRNA in a specific complex has been
      revealed.

PMID- 9613589
TI  - Expression of skeletal muscle-type voltage-gated Na+ channel in rat and human
      prostate cancer cell lines.
AB  - Previous electrophysiological work has demonstrated expression of a voltage-gated
      Na+ channel (VGSC) specifically in two highly metastatic prostatic epithelial
      tumour cell lines: MAT-LyLu (rat) and PC-3 (human). However, the identity of the
      channel(s) present was uncertain. The present study used a combination of
      molecular biological techniques to demonstrate that full-length skeletal muscle
      type 1 (SkM1) VGSC mRNA is present in the mRNA pool of the MAT-LyLu cell line.
      mRNA for this particular channel type was also expressed in the PC-3 cells. In
      situ hybridisation data suggested that the level and pattern of rSkM1 mRNA
      expression were different in the Dunning cells of markedly different metastatic
      potential. Interestingly, the same type of mRNA was also detected in the weakly
      metastatic counterparts of the cells: AT-2 (rat) and LNCaP (human).

PMID- 9613590
TI  - Purification and characterization of sulfide dehydrogenase from alkaliphilic
      chemolithoautotrophic sulfur-oxidizing bacteria.
AB  - Extracts of the alkaliphilic sulfur-oxidizing autotroph strain AL3 contained
      sulfide:cytochrome c oxidoreductase. This was active above pH 8, and was
      associated with the cell membranes. Although up to 60% of the initial activity
      was lost during Triton X-100 extraction, further purification resulted in an
      enzyme that catalyzed sulfide oxidation with horse heart cytochrome c. This
      enzyme was a 41 kDa protein containing heme c554. The optimum pH of the membrane
      bound enzyme was 9.0, but after extraction this fell to 8.0. The enzyme catalyzed
      a single electron oxidation of HS-. Hydrosulfide radical is therefore the most
      probable product.

PMID- 9613591
TI  - Transcriptional regulation of the heavy subunit chain of gamma-glutamylcysteine
      synthetase by ionizing radiation.
AB  - Since glutathione (GSH) protects against oxidative stress, we determined the
      regulation of cellular GSH by ionizing radiation in human hepatoblastoma cells,
      HepG2. The levels of GSH increased in irradiated HepG2 due to a greater gamma
      glutamylcysteine synthetase (gamma-GCS) activity, which was paralleled by gamma
      GCS heavy subunit chain (gamma-GCS-HS) mRNA levels. Transcription of deletion
      constructs of the gamma-GCS-HS promoter cloned in a reporter vector was
      associated with activator protein-1 (AP-1), consistent with the DNA binding of AP
      1 in nuclear extracts of irradiated HepG2. Hence, the transcriptional regulation
      of gamma-GCS by ionizing radiation emerges as an adaptive mechanism, which may be
      of significance to control the consequences of the oxidative stress induced by
      radiation.

PMID- 9613592
TI  - Carbohydrate induced modulation of cell membrane VII. Binding of exogenous lectin
      increases osmofragility of erythrocytes.
AB  - Due to their multivalent binding character, lectins when added exogenously will
      cross-link membrane surface receptors leading to lateral molecular
      reorganizations in the plane of the bilayer. This study reports for the first
      time that agglutination of rabbit erythrocytes by lentil lectin and concanavalin
      A increases their osmofragility. Increase in osmofragility was detected by
      measuring the hemolysis of erythrocytes in hypotonic as well as in isotonic
      solutions. It was also found that agglutination per se does not increase
      osmofragility but the binding of legume lectin is essential since human Rh+ cells
      agglutinated by a monoclonal antibody do not exhibit hemolysis.

PMID- 9613593
TI  - Differences in chain length distribution of inulin from Cynara scolymus and
      Helianthus tuberosus are reflected in a transient plant expression system using
      the respective 1-FFT cDNAs.
AB  - A newly isolated cDNA clone, Cy3, encoding the fructan fructan 1
      fructosyltransferase (1-FFT) from artichoke was expressed using tobacco
      protoplasts as expression system. Analysis of the inulin molecules synthesized
      upon incubation of protoplast extracts with a mixture of oligofructans (DP3-5)
      shows the production of inulins with a degree of polymerization (DP) of up to 23,
      whereas parallel experiments performed using a 1-FFT cDNA from Jerusalem
      artichoke led to the production of fructans with a DP of up to only 12. The
      results of in vitro fructan synthesis catalyzed by transiently expressed enzymes
      therefore reflect the difference of in vivo fructan composition of Jerusalem
      artichoke (M(DP) = 8-10) and artichoke (M(DP) = 65). These data suggest that the
      fructan pattern in a given species is mainly defined by the enzymatic
      characteristics of 1-FFT.

PMID- 9613594
TI  - Activation of bcl-2 suppressible 40 and 44 kDa p38-like kinases during apoptosis
      of early and late B lymphocytic cell lines.
AB  - Activation of several different kinases characterizes the induction of apoptosis.
      Abelson virus transformed pre-B lymphocytes undergo apoptosis within 24 h of
      serum deprivation, PKA activation or gamma-irradiation, and the activity of two
      kinases of ca. 40 and 44 kDa is specifically induced during this apoptotic
      process. Bcl-2 expression prevents both apoptosis and the induction of these
      kinases. Immunologic and substrate similarities indicate that these kinases are
      related to the p38 family of MAP kinases. More mature cells of the B lymphocytic
      lineage, plasmacytomas, also exhibit induction of these kinases when apoptosis is
      induced by withdrawal of serum or IL-6. Treatment of the pre-B cells with ICE
      protease inhibitors when apoptotic stimuli are delivered prevents induction of
      the kinase activity, and partially inhibits apoptosis. These findings indicate
      that the induction of these 40 and 44 kDa p38 related kinases is a common feature
      of apoptosis in mouse B lymphocytic cells and may represent a step downstream of
      ICE proteases in the signal cascade that leads to programmed cell death.

PMID- 9613595
TI  - Beta structure motif recognition by anti-gliadin antibodies in coeliac disease.
AB  - A 20-amino acid synthetic peptide from the N-terminal region of gamma3 avenin
      yields a surprisingly strong reactivity with anti-gliadin antibodies (AGA) of
      coeliac sera, comparable to that of a gliadin extract. In contrast, a low
      reactivity is observed with five similar peptides derived from alpha-gliadin,
      gamma70 and omega1 secalins. Circular dichroism studies of these peptides show
      that the avenin peptide displays the highest beta-turn content (30%), while other
      peptides yield much lower values. In agreement with circular dichroism data,
      nuclear magnetic resonance data point to the presence of a beta-turn in the
      avenin peptide DPSEQ segment, a sequence with a high statistical beta-turn
      preference. A strong linear dependence between AGA reactivity and beta-turn
      content was observed for these peptides, indicating for the first time a role of
      beta-turn motifs in anti-gliadin antibodies recognition in coeliac disease. This
      suggests that circulating AGA in coeliac patients comprise not only linear but
      also conformational antibodies against beta-turn motifs. Polyclonal antibodies
      raised against the avenin peptide containing beta-turn motifs react by
      immunoblotting with all gliadin, hordein and secalin proteins, which are rich in
      beta-turn conformations, despite that their primary structures are unrelated to
      that of the peptide.

PMID- 9613596
TI  - The K-ATP channel regulates the effect of Ca2+ on gap junction permeability in
      cultured astrocytes.
AB  - Using the scrape-loading technique we show that tolbutamide and glybenzcyclamide,
      two inhibitors of the K+ channel sensitive to ATP (K-ATP channel), partially
      prevent the inhibition of gap junction permeability promoted by Ca2+ in cultured
      astrocytes. This effect was dose-dependent, reaching a maximum at 400 microM and
      1 microM of tolbutamide and glybenzcyclamide, respectively. The presence of the
      Ca2+ ionophore A-23187 strongly reduced the concentration of Ca2+ required to
      block gap junction permeability but did not abolish the effect of tolbutamide and
      glybenzcyclamide. These results suggest that the effect of these two compounds
      are not brought about by control of the intracellular concentration of Ca2+ but
      probably by the promotion of plasma membrane depolarization.

PMID- 9613597
TI  - Quantitative analysis of thrombopoietin receptors on human megakaryocytes.
AB  - Thrombopoietin (TPO), or c-MPL ligand, is the primary regulator of megakaryocyte
      and platelet production. TPO receptors expressed on human megakaryocytes derived
      from peripheral blood (PB) and cord blood (CB) progenitors cultured in the
      presence of TPO have now been analyzed quantitatively. Like those on human PB
      platelets, TPO receptors on the cultured megakaryocytes exhibited a molecular
      mass of approximately 80 kDa. Various characteristics of PB- and CB-derived
      megakaryocytes indicated that the former were more mature than the latter. Both
      PB- and CB-derived megakaryocytes expressed a single class of high-affinity TPO
      receptors, with 1933 +/- 772 (n = 3) and 184 +/- 48 (n = 4) sites per cell,
      respectively. These data indicate that the number of TPO receptors on human
      megakaryocytes increases with cell maturation.

PMID- 9613598
TI  - Characterization of random-sequence proteins displayed on the surface of
      Escherichia coli RNase HI.
AB  - In a previous study, random-sequence proteins of 120-130 amino acid residues were
      inserted into the surface loop region of the enzyme, Escherichia coli RNase HI
      [Doi et al. (1997) FEBS Lett. 402, 177-1801. Here we established that the RNase H
      activity of the insertion mutants is correlated with their secondary structure
      contents evaluated by circular dichroism measurement at 222 nm. The random
      sequence insert of a mutant enzyme possessing relatively high RNase H activity
      was detached from the RNase HI scaffold, and its characterization indicated that
      the random-sequence protein maintains its secondary structure after separation
      from the scaffold. Thus, the structural features of random-sequence proteins were
      suggested to be monitored by measuring the activity of the scaffold enzyme into
      which these proteins have been inserted.

PMID- 9613599
TI  - Interaction between an intraluminal loop peptide of the inositol 1,4,5
      trisphosphate receptor and the near N-terminal peptide of chromogranin A.
AB  - The near N-terminal region of chromogranin A (CGA) has been shown to be the
      secretory vesicle membrane binding region, and tetrameric chromogranin A has been
      demonstrated to bind four molecules of an intraluminal loop peptide of the
      inositol 1,4,5-trisphosphate (IP3) receptor. It was therefore necessary to
      determine whether the conserved near N-terminal region of CGA interacts with the
      intraluminal loop region of the IP3 receptor. In the present study, we found that
      the proposed anchor region of CGA, the conserved near N-terminal region, does
      indeed interact with the intraluminal loop region of the IP3 receptor at the
      intravesicular pH of 5.5, further strengthening the case for the potential
      interaction between tetrameric chromogranins and tetrameric IP3 receptors in the
      cell.

PMID- 9613600
TI  - Flash-induced voltage changes in halorhodopsin from Natronobacterium pharaonis.
AB  - The flash-induced voltage response of halorhodopsin at high NaCl concentration
      comprises two main kinetic components. The first component with tau approximately
      1 micros does not exceed 4% of the overall response amplitude and is probably
      associated with the formation of the L (hR520) intermediate. The second main
      component with tau approximately 1-2.5 ms which is independent of Cl-
      concentration can be ascribed to the transmembrane Cl- translocation during the L
      intermediate decay. The photoelectric response in the absence of Cl- has the
      opposite polarity and does not exceed 6% of the overall response amplitude at
      high NaCl concentration. A pH decrease results in substitution of the Cl(-)
      dependent components by the photoresponse which is similar to that in the absence
      of Cl-. Thus, the difference between photoresponses of chloride-binding and
      chloride-free halorhodopsin forms resembles that of bacteriorhodopsin purple
      neutral and blue acid forms, respectively. The photovoltage data obtained can
      hardly be explained within the framework of the photocycle scheme suggested by
      Varo et al. [Biochemistry 34 (1995), 14490-14499]. We suppose that the O-type
      intermediate belongs to some form of halorhodopsin incapable of Cl- transport.

PMID- 9613601
TI  - Reconstitution of F1-ATPase activity from Escherichia coli subunits alpha, beta
      and subunit gamma tagged with six histidine residues at the C-terminus.
AB  - An engineered gamma subunit of Escherichia coli F1-ATPase with extra 14 and 20
      amino acid residues at the N- and C-termini (His-tag gamma), respectively, was
      overproduced in E. coli and purified. Six histidines are included in the C
      terminal extension. The reconstituted F1 containing alpha, beta, and His-tagged
      gamma exhibited sixty percent of the wild-type ATPase activity. The reconstituted
      alphabeta His-tag gamma complex was subjected to affinity chromatography with
      nickel-nitrilotriacetic acid (Ni-NTA) agarose resin. ATPase activity was eluted
      specifically with imidazole. These results implied that the tag sequence
      protruded to the surface of the complex and did not seriously impair the
      activity. The reconstituted alphabeta His-tag gamma complex, even after its
      binding to the resin, exhibited ATPase activity suggesting that the gamma
      subunit, when fixed to a solid phase, may rotate the alphabeta complex. This
      system may provide a new approach for analysis of the rotation mechanisms in F1
      ATPase.

PMID- 9613602
TI  - The alpha(2D/A)-adrenergic receptor-linked membrane guanylate cyclase: a new
      signal transduction system in the pineal gland.
AB  - In the pineal gland, the membrane guanylate cyclase activity was specifically
      stimulated by alpha(2D/A)-adrenergic receptor (alpha(2D/A)-AR) agonists. The
      agonists, however, did not stimulate the cyclase activity in the cell-free
      membranes. It was possible to stimulate the cyclase in cell-free membranes by the
      addition of the pineal soluble fraction, but this stimulation was Ca2+-dependent
      and alpha(2D/A)-agonist-independent. It was also possible to achieve Ca2+
      dependent stimulation of the cyclase by the direct addition of CD-GCAP to the
      isolated pineal membranes. CD-GCAP is a Ca2+-binding protein and is a specific
      activator of one of the two members of the ROS-GC subfamily of membrane guanylate
      cyclases, ROS-GC1. The soluble fraction of the pineal gland stimulated
      recombinant ROS-GC1 in a Ca2+-dependent fashion. The direct presence of both ROS
      GC1 and CD-GCAP in the pineal was established by molecular cloning/PCR studies.
      The findings demonstrate the existence of a novel signal transduction mechanism-
      the linkage of the alpha(2D/A)-AR signaling system with ROS-GC1 transduction
      system, occurring through intracellular Ca2+ via CD-GCAP.

PMID- 9613603
TI  - The pyridoxal-5'-phosphate-dependent catalytic antibody 15A9: its efficiency and
      stereospecificity in catalysing the exchange of the alpha-protons of glycine.
AB  - 13C-NMR has been used to follow the exchange of the alpha-protons of [2
      (13)C]glycine in the presence of pyridoxal-5'-phosphate and the catalytic
      antibody 15A9. In the presence of antibody 15A9 the 1st order exchange rates for
      the rapidly exchanged proton of [2-(13)C]glycine were only 25 and 150 times
      slower than those observed with tryptophan synthase (EC 4.2.1.20) and serine
      hydroxymethyltransferase (EC 2.1.2.1). The catalytic antibody increases the 1st
      order exchange rates of the alpha-protons of [2-(13)C]glycine by at least three
      orders of magnitude. We propose that this increase is largely due to an entropic
      mechanism which results from binding the glycine-pyridoxal-5'-phosphate Schiff
      base. The 1st and 2nd order exchange rates of the pro-2S proton have been
      determined but we were only able to determine the 2nd order exchange rate for the
      pro-2R proton of glycine. In the presence of 50 mM glycine the antibody
      preferentially catalyses the exchange of the pro-2S proton of glycine. The
      stereospecificity of the 2nd order exchange reaction was quantified and we
      discuss mechanisms which could account for the observed stereospecificity.

PMID- 9613604
TI  - Cloning and functional expression of a 'fast' fungal kinesin.
AB  - Conventional kinesins are molecular motors that move towards the plus end of
      microtubules. In animal species, they have been shown to be remarkably conserved
      in terms of both their primary sequence and several physiological properties,
      including their velocity of movement. Here we report the cloning of Synkin, a
      homologue of conventional kinesin from the zygomycete fungus Syncephalastrum
      racemosum [Steinberg, Eur. J. Cell Biol. 73 (1997) 124-131] that is 4-5 times
      faster than its animal counterparts. Expression in bacteria yields a fully
      functional motor that moves at the same speed as the native motor isolated from
      fungal hyphae and has similar hydrodynamic properties. Its sequence is most
      closely related to that of two other fungal kinesins from Neurospora and
      Ustilago, and shares several biochemical properties with the Neurospora motor.
      Fungal kinesins therefore seem to form a conserved subfamily of conventional
      kinesins distantly related to animal kinesins. They may help to identify sequence
      features important for determining motor velocity.

PMID- 9613605
TI  - Cross-linking and mutational analysis of the oligomerization state of the
      cytokine macrophage migration inhibitory factor (MIF).
AB  - The structure of the cytokine MIF has been investigated by X-ray crystallography,
      NMR, and biochemical methods with conflicting results regarding the structural
      and functional oligomerization state of this protein. Determination of the
      oligomeric state(s) is important for understanding more precisely the molecular
      mechanism of MIF action. To address this issue, we performed cross-linking of
      human and mouse MIF and selected mutants by various methods and analyzed the
      oligomerization by SDS-PAGE and gel filtration. MIF was found to form a mixture
      of monomeric, dimeric, and trimeric states at physiological concentrations, with
      the monomer and dimer representing the major species. Similar results were
      obtained when the carboxy-truncated mutants MIF(1-104) and MIF(1-109) were
      examined, indicating that the C-terminus of MIF is not critical for trimer
      stabilization. Cross-linking analysis of the isosteric Cys --> Ser mutants C56S
      and C80S of human MIF resulted in a similar oligomer distribution, whereas
      substitution of Cys59 led to a significant reduction in the dimeric and trimeric
      forms, indicating that the hydrophobic region around Cys59 is important for the
      oligomerization of MIF. Together, our data argue that physiological MIF solutions
      contain a mixture of monomers, dimers, and trimers.

PMID- 9613606
TI  - Differential gene expression of a human alpha2,3-sialyltransferase in leukaemic
      cell lines and leucocytes.
AB  - The gene expression of the human Gal beta1,4(3)GlcNAc/Gal beta1,3GalNAc alpha-2,3
      sialyltransferase was investigated in the leukaemic cell lines HL60, K-562, MOLT
      4, THP-1 and in blood leucocytes. Five different transcripts were identified. In
      HL60 and THP-1 cells the expression levels of two of these changed during
      differentiation. Two potential AP1 binding sites were detected in the promoter
      regions of the gene. THP-1 cells contain proteins binding with higher affinities
      to these sequences in the sialyltransferase gene than to the AP1 consensus
      sequence, whereas nuclear extracts from HL60 cells have the opposite affinity.

PMID- 9613607
TI  - Functional coupling between human E-type Ca2+ channels and mu opioid receptors
      expressed in Xenopus oocytes.
AB  - Neuronal alpha1E Ca2+ channels were expressed in Xenopus laevis oocytes alone and
      in combination with the mu opioid receptor. Macroscopic currents were recorded
      under voltage clamp conditions. The stimulation of the morphine receptor by the
      synthetic [D-Ala2,N-Me-Phe4,Gly-ol5] enkephalin (DAMGO) produced a 20% reduction
      in the alpha1E ionic current. This effect was associated with a large change in
      the decay phase of the Ba2+ current. The effect of 1 microM DAMGO was fully
      antagonized by the universal mu opioid receptor antagonist naloxone and by the
      selective antagonist beta-funaltrexamine. The ionic current inhibition induced by
      DAMGO was partially recovered by preceding strong depolarizations. The injection
      of the catalytic subunit of pertussis toxin (A-protomer) abolished the effect of
      DAMGO, suggesting the involvement of a GTP binding protein in the alpha1E
      modulation. The coexpression of the regulatory beta2a Ca2a channel subunit,
      together with the alpha1E subunit and the mu opioid receptor, prevented the
      reduction of the ionic current following the receptor stimulation with DAMGO,
      whereas the coexpression with the beta3 subunit reduced by approximately 50% the
      modulatory effect of DAMGO. The effect produced by the stimulation of the opioid
      receptor could be mimicked by coexpressing the alpha1E channel with the G-protein
      betagamma subunits.

PMID- 9613608
TI  - Peptide binding consensus of the NHE-RF-PDZ1 domain matches the C-terminal
      sequence of cystic fibrosis transmembrane conductance regulator (CFTR).
AB  - The Na+-H+ exchanger regulatory factor (NHE-RF) is a cytoplasmic phosphoprotein
      that was first found to be involved in protein kinase A mediated regulation of
      ion transport. NHE-RF contains two distinct protein interaction PDZ domains: NHE
      RF-PDZ1 and NHE-RF-PDZ2. However, their binding partners are currently unknown.
      Because PDZ domains usually bind to specific short linear C-terminal sequences,
      we have carried out affinity selection of random peptides for specific sequences
      that interact with the NHE-RF PDZ domains and found that NHE-RF-PDZ1 is capable
      of binding to the CFTR C-terminus. The specific and tight association suggests a
      potential regulatory role of NHE-RF in cystic fibrosis transmembrane conductance
      regulator (CFTR) function.

PMID- 9613609
TI  - A new system for the measurement of electrogenicity produced by ion pumps using a
      thin polymer film: examination of wild type bacteriorhodopsin and the D96N mutant
      over a wide pH range.
AB  - We developed a new assay system for the measurement of capacitive electric
      currents generated by ion pumps using the thin polymer film 'Lumirror' (Toray
      Co., Japan). This system enables us to examine the electrogenicity of ion pumps
      over a wide range of experimental conditions with high reproducibility due to the
      mechanical and chemical stability, the high electric resistance and the high
      electric capacitance of the thin polymer film. Using this method, we examined the
      photoelectric response of wild type bacteriorhodopsin and its D96N mutant over a
      wide pH range (2.8-10.0). The results were explained in terms of the affinities
      of the proton binding sites for translocated protons. A possibility that the
      direction of the proton transfer from the Schiff base was influenced by the
      protonation/deprotonation state of the surrounding proton binding sites was
      suggested. We also found that this film can be used as a substrate for atomic
      force microscopy (AFM) samples and hence the active purple membrane was observed
      with AFM.

PMID- 9613610
TI  - Critical amino acid residues of AIP, a highly specific inhibitory peptide of
      calmodulin-dependent protein kinase II.
AB  - The importance of the individual amino acid residues of AIP (KKALRRQEAVDAL), a
      highly specific inhibitor of calmodulin-dependent protein kinase II (CaMKII), was
      studied. Replacement of Arg6, Gln7, or Ala9 by other amino acid residues produced
      a marked increase in the IC50 value. Leu4 and Val10 were also sensitive to
      replacement, but some hydrophobic amino acids could substitute for these
      residues. Although replacement of Ala3, Glu8, Ala12, and Leu13 by other residues
      produced no significant increase in the IC50, the substitution of Lys for Ala3
      decreased the IC50. An AIP analog (KKKLRRQEAFDAY), in which Ala3 and Val10 were
      replaced with Lys and Phe, respectively, showed an IC50 value as low as 4 nM,
      suggesting that it is a useful tool for studying the physiological roles of
      CaMKII.

PMID- 9613611
TI  - Somatic and germline clone analysis in mutants of the S-adenosylmethionine
      synthetase encoding gene in Drosophila melanogaster.
AB  - We have analysed the phenotypic consequences of homozygous mutant clones in the S
      adenosylmethionine synthetase encoding gene in Drosophila melanogaster. The
      results suggest that SamS function is required for cell proliferation/growth in
      embryonic/early larval cells and during development of imaginal disc cells.
      Homozygous SamS germline clones can, however, develop and give rise to viable
      heterozygous offspring. This offspring expresses a Minute-like phenotype. We
      suggest that this phenotype is caused by an obstruction of the polyamine
      biosynthesis.

PMID- 9613612
TI  - APO2 ligand: a novel lethal weapon against malignant glioma?
AB  - APO2L (TRAIL) is a novel CD95L (Fas/APO-1-L) homologous cytotoxic cytokine that
      interacts with various receptors which transmit (DR4, DR5) or inhibit (DcR1,
      DcR2) an apoptotic signal. Here, we report that human glioma cell lines
      preferentially express mRNAs for agonistic death receptors DR4 (8/12) and DR5
      (11/12) rather than the death-inhibitory decoy receptors DcR1 (4/12) and DcR2
      (2/12). Ten of 12 cell lines are susceptible to APO2L-induced apoptosis. The
      resistant cell lines, U138MG and U373MG, are cross-resistant to CD95L-induced
      apoptosis. Similar to CD95L-induced apoptosis, APO2L-induced apoptosis is
      inhibited by ectopic expression of the caspase inhibitor, crm-A, or of bcl-2, or
      by coexposure to the corticosteroid, dexamethasone, or the lipoxygenase
      inhibitor, nordihydroguaretic acid. There is no correlation between p53 genetic
      status of the cell lines and their susceptibility to APO2L-induced apoptosis, but
      the latter is moderately enhanced by ectopic expression of wild-type p53. APO2L
      targeting may be a promising approach for selectively targeting apoptosis to
      human malignant glioma cells.

PMID- 9613613
TI  - Characterisation of gamma-glutamylcysteine synthetase-heavy subunit promoter: a
      critical role for AP-1.
AB  - The 5'-flanking region of human gamma-glutamylcysteine synthetase-heavy subunit
      (gamma-GCS-HS) was characterised by creating a series of chloramphenicol acetyl
      transferase (CAT) reporter deletion constructs. Analysis of various deleted CAT
      constructs revealed that a putative AP-1 consensus sequence is required to direct
      the constitutive and oxidant-mediated promoter activity. Gel mobility shift and
      mutation analysis of the sequence (-269 to -263 bp), showed binding of AP-1 is
      involved in the oxidant-mediated regulation of gamma-GCS-HS promoter activity.

PMID- 9613614
TI  - Multi-antennary Gal beta1-->4GlcNAc and Gal beta1-->3GalNAc clusters as important
      ligands for a lectin isolated from the sponge Geodia cydonium.
AB  - The affinity of a lectin from the sponge Geodia cydonium (GCL-I) for multi
      antennary Gal beta1-->4GlcNAc and Gal beta1-->3GalNAc ligands was studied by both
      the biotin/avidin-based microtiter plate lectin binding assay and the inhibition
      of lectin-glycoform interaction. Among the glycoforms tested for binding, GCL-I
      reacted strongly with three multi-antennary Gal beta1-->4GlcNAc clusters
      containing glycoproteins (asialo human and bovine alpha1-acid gps and asialo
      fetuin), T (Gal beta1-->3GalNAc) rich glycoprotein from porcine salivary gland,
      asialo bird nest gp, and human blood group A active cyst gp, while human and
      bovine alpha1-acid gps, fetuin, and Tn containing gps were inactive. Among the
      haptens tested for inhibition, tri-antennary Gal beta1-->4GlcNAc (Tri-II) was
      about 1500, 72, and 72 times more active than GalNAc, Gal beta1-->4GlcNAc (II),
      and Gal beta1-->3GalNAc (T), respectively. Based on the present and previous
      results, it is proposed that tri-antennary Gal beta1-->4GlcNAc and Gal beta1-
      >3GalNAc clusters, in addition to GalNAc alpha1-->3GalNAc and GalNAc alpha1-
      >3Gal, are also important ligands for binding; and sialic acid of glycoprotein
      does interfere with binding.

PMID- 9613615
TI  - A deficiency in Syk enhances ceramide-induced apoptosis in DT40 lymphoma B cells.
AB  - Syk deficiency significantly enhanced ceramide-induced apoptosis. Ectopic
      expression of wild-type or kinase-inactive Syk rendered Syk-negative cells
      resistant to ceramide-induced apoptosis. Furthermore, ceramide could not activate
      Syk, indicating that Syk protected DT40 cells from ceramide-induced apoptosis,
      via a mechanism independent of its activity. In addition, a deficiency in Lyn
      also resulted in the cells becoming susceptible to ceramide-induced apoptosis.
      However, no difference of Ara-C-induced apoptosis between wild-type and mutant
      cells was observed. c-Jun N-terminal kinases appeared not to be important in
      mediating the enhanced apoptosis, as they were still activated in mutant cells
      following ceramide treatment.

PMID- 9613616
TI  - Homologous p35 proteins of baculoviruses show distinctive anti-apoptotic
      activities which correlate with the apoptosis-inducing activity of each virus.
AB  - The anti-apoptotic activity of p35s from two baculoviruses, Autographa
      californica nucleopolyhedrovirus (AcNPV) and Bombyx mori NPV (BmNPV), was
      compared in mammalian cells. AcNPV p35 efficiently blocked apoptosis induced by
      caspase overexpression, but BmNPV p35 did so very poorly. Analysis of chimeric
      p35s and in vitro cleavage of wild type p35s suggest that the cleavage efficiency
      of p35 correlates with the blocking activity. Single amino acid substitutions of
      BmNPV p35 with those observed in AcNPV p35, however, resulted in significant loss
      of its anti-apoptotic activity. We speculate that sequences flanking the cleavage
      site have uniquely evolved during baculovirus evolution.

PMID- 9613617
TI  - Primary structure of a potassium channel toxin from the sea anemone Actinia
      equina.
AB  - A potassium channel toxin (AeK) was isolated from the sea anemone Actinia equina
      by gel filtration on Sephadex G-50 and reverse-phase HPLC on TSKgel ODS-120T. AeK
      and alpha-dendrotoxin inhibited the binding of 125I-alpha-dendrotoxin to rat
      synaptosomal membranes with IC50 of 22 and 0.34 nM, respectively, indicating that
      AeK is about sixty-five times less toxic than alpha-dendrotoxin. The complete
      amino acid sequence of AeK was elucidated; it is composed of 36 amino acid
      residues including six half-Cys residues. The determined sequence showed that AeK
      is analogous to the three potassium channel toxins from sea anemones (BgK from
      Bunodosoma granulifera, ShK from Stichodactyla helianthus and AsKS from Anemonia
      sulcata), with an especially high sequence homology (86%) with AsKS.

PMID- 9613618
TI  - Response to "Substance abuse and schizophrenia: editors' introduction".

PMID- 9613619
TI  - New models of the pathophysiology of schizophrenia: editors' introduction.
AB  - New models of the pathogenesis of schizophrenia are presented. These models
      represent hypotheses intended to stimulate discussion and new experimentation.
      Each of the contributions approach the pathophysiology of schizophrenia from a
      unique perspective. Yet, all of them emphasize the integration of new advances in
      basic neuroscience, the functional neuroanatomy of schizophrenia, and information
      drawn from new biotechnologies, such as neuroimaging and molecular genetics, to
      provide unique insights into schizophrenia. In each case, the novel hypotheses
      proposed also illustrate the continuing need for a better understanding of the
      dynamic interaction between synaptic plasticity and neural circuitry to further
      our understanding of the human brain in health and disease.

PMID- 9613620
TI  - Schizophrenia, sensory gating, and nicotinic receptors.
AB  - A series of human and animal investigations has suggested that altered expression
      and function of the alpha7-nicotinic cholinergic receptor may be responsible for
      the auditory sensory gating deficit characterized in schizophrenia patients and
      their relatives as diminished suppression of an auditory-evoked response (P50) to
      repeated stimuli. This finding, in conjunction with evidence for familial
      transmission of this sensory gating deficit, suggests a pathogenic role of the
      gene for the alpha7-nicotinic receptor in schizophrenia. This article considers
      the possible effects of this dysfunction in a broader context. Not only is this
      dysfunction consistent with difficulties in sensory gating, but it might also
      predispose patients to problems with learning efficiency and accuracy. Such
      learning problems could underlie schizophrenia patients' delusional thinking,
      hallucinations, and social dysfunction. In addition, heavy smoking in many
      schizophrenia patients is consistent with the high concentration of nicotine
      necessary to activate the receptor and with the receptor's extremely rapid
      desensitization. Finally, the receptor's possible role in cell growth and
      differentiation should be considered in connection with developmental deficits
      and other cellular abnormalities in schizophrenia.

PMID- 9613621
TI  - "Cognitive dysmetria" as an integrative theory of schizophrenia: a dysfunction in
      cortical-subcortical-cerebellar circuitry?
AB  - Earlier efforts to localize the symptoms of schizophrenia in a single brain
      region have been replaced by models that postulate a disruption in parallel
      distributed or dynamic circuits. Based on empirical data derived from both
      magnetic resonance and positron emission tomography, we have developed a model
      that implicates connectivity among nodes located in prefrontal regions, the
      thalamic nuclei, and the cerebellum. A disruption in this circuitry produces
      "cognitive dysmetria," difficulty in prioritizing, processing, coordinating, and
      responding to information. This "poor mental coordination" is a fundamental
      cognitive deficit in schizophrenia and can account for its broad diversity of
      symptoms.

PMID- 9613622
TI  - Model generation and testing to probe neural circuitry in the cingulate cortex of
      postmortem schizophrenic brain.
AB  - In the past decade, there has been increased interest in whether discreet
      alterations of neural circuitry might play a role in the pathophysiology of
      schizophrenia. In the absence of a readily identifiable histopathology, a variety
      of sophisticated neurobiological approaches is being applied to the study of this
      disorder. In one series of investigations, subtle abnormalities have been
      detected in the anterior cingulate cortex-layer II (ACCx-II) of schizophrenia
      patients. One of these studies suggested a reduction of nonpyramidal neurons in
      schizophrenia patients, and it was postulated that this change could give rise to
      a relative increase of dopaminergic inputs to the remaining gamma-aminobutyric
      acid (GABA) cells. Although empiric evidence in support of this hypothesis was
      obtained, a subsequent post hoc analysis, described in this report, has suggested
      that this change could have occurred irrespective of whether GABA cells are
      reduced in number. A shift of cortical dopamine afferents from pyramidal to
      nonpyramidal neurons in ACCx-II seems to provide a more plausible explanation for
      such a "miswiring." These findings support critical use of model generation and
      testing as powerful tools for unraveling the nature of altered neural circuitry
      in postmortem schizophrenic brain.

PMID- 9613624
TI  - Integrating schizophrenia.
AB  - A neuropsychological theory of the positive symptoms of schizophrenia proposed by
      J.A. Gray et al. is reviewed in light of subsequent evidence from studies of
      latent inhibition in clinical populations, healthy volunteers, and rats. It is
      clear that disrupted latent inhibition is associated with psychosis, but it is
      uncertain whether this is a state or a trait marker. Much evidence indicates that
      a similar disruption in latent inhibition can be provoked in rats by excess
      release of dopamine in the nucleus accumbens, and conversely, that potentiation
      of latent inhibition occurs when dopaminergic transmission is blocked in this
      structure. The projection from the hippocampal system to the nucleus accumbens
      also plays a role in latent inhibition. The theory, therefore, is broadly
      supported by recent findings. The resulting model of schizophrenia is discussed
      in relation to the contents of consciousness, positive psychotic symptoms, and
      alternative theories.

PMID- 9613623
TI  - Limbic-cortical neuronal damage and the pathophysiology of schizophrenia.
AB  - Neurobiological studies of patients with schizophrenia suggest that abnormalities
      of both anatomy and function occur in limbic-cortical structures. An anatomical
      circuit links the functioning of the ventral striatum (i.e., nucleus accumbens)
      with the hippocampus and other limbic-cortical structures where neurobiological
      abnormalities have been found. In animals, lesions of limbic-cortical neurons
      cause decreases in glutamatergic input to the nucleus accumbens and are also
      associated with decreases in presynaptic dopamine release, increases in the
      density of D2-like dopamine receptors, and insensitivity to the actions of
      dopamine antagonists such as haloperidol. These experiments suggest a plausible
      pathophysiology of schizophrenia, in that schizophrenic symptoms may be caused by
      an abnormal dopaminergic state brought about by a primary limbic-cortical lesion
      and deficits in glutamatergic inputs to the ventral striatum.

PMID- 9613625
TI  - Dysfunctions in multiple interrelated systems as the neurobiological bases of
      schizophrenic symptom clusters.
AB  - The absence of an animal model that accurately approximates schizophrenia limits
      current research into the pathophysiology of this disorder. Obviously, the
      cognitive disturbances associated with schizophrenia are difficult to evaluate in
      laboratory animals. Nonetheless, animal studies have provided insight into the
      anatomy and physiology of the brain systems that have been implicated in
      schizophrenia. These studies also suggest how brain systems may be involved in
      information processing in normal and pathological conditions. Thus, a careful
      assessment of the properties and functions of the brain regions suggested to be
      involved in schizophrenic symptoms has been a primary objective in several
      laboratories. In this review, we discuss the interactions among the brain regions
      implicated in schizophrenia--the ventral striatum, prefrontal cortex,
      hippocampus, and dopamine systems--and provide an integrative model linking
      altered function in these regions with specific clusters of symptoms of
      schizophrenia.

PMID- 9613626
TI  - Using an animal model of deficient sensorimotor gating to study the
      pathophysiology and new treatments of schizophrenia.
AB  - Certain animal models can greatly enhance our understanding of the neurobiology
      of schizophrenia and can be used to predict the antipsychotic activity of
      compounds. Prepulse inhibition (PPI), the reduction in startle produced by a
      prepulse stimulus, is diminished in schizophrenia patients. Theoretically,
      deficient PPI in schizophrenia patients is a measure of the loss of sensorimotor
      gating that may lead to sensory flooding and cognitive fragmentation. In rats,
      PPI is disrupted by systemic administration of dopamine agonists, serotonin
      agonists, or glutamate antagonists and by a variety of surgical or
      pharmacological manipulations of neural circuitry linking the limbic cortex,
      striatum, pallidum, and pontine reticular formation. This article describes
      several different ways the loss of PPI in rats can be used as a model for
      studying the pathophysiology and neurobiology of impaired sensorimotor gating in
      schizophrenia patients and for predicting antipsychotic activity in novel
      compounds. First, new experimental strategies may be used to distinguish
      behavioral profiles of "typical" versus "atypical" antipsychotics. Second, this
      paradigm can be used to study the effects of early developmental insults-
      including neonatal lesions and isolated rearing--on the adult emergence of
      deficient sensorimotor gating. Third, using different animal strains and species,
      as well as gene "knockout" strategies, greatly increases our ability to
      understand specific genetic or receptor contributions to the regulation of
      deficient PPI. Each of these uses of the PPI paradigm is enhanced by studies of
      the basic brain substrates that regulate PPI in rats and by the increasingly
      sophisticated assessments of PPI and related measures in schizophrenia spectrum
      patients.

PMID- 9613627
TI  - A candidate molecule approach to defining developmental pathology in
      schizophrenia.
AB  - The evidence that schizophrenia may have its origins from early in life, possibly
      during prenatal brain development, is based primarily on a constellation of
      nonspecific anatomical findings and on the results of surveys of obstetrical
      complications and of childhood neurological and psychological adjustment. The
      developmental processes implicated by this evidence are uncertain, but
      speculation has centered around abnormalities of neuronal proliferation,
      migration, and connection formation. These developmental milestones are the
      results of complicated cellular processes involving molecular interactions
      between cells and between the extracellular and intracellular milieus. To
      understand how these abnormalities could relate to schizophrenia, it is necessary
      to characterize the molecular events that define the processes. In this article,
      we discuss the potential impact of a number of molecules that are important in
      the sequence of cellular events implicated in schizophrenia. In particular, we
      focus on molecular mechanisms related to cell proliferation, axonal outgrowth,
      cell migration, cell survival, synaptic regression, myelination, and
      developmental aspects of early adult life. These various candidate molecules
      regulate different aspects of cell growth and cell-cell interactions and are
      involved in the regulation of deoxyribonucleic acid (DNA) expression. Very few of
      these molecules have been studied in the schizophrenic brain.

PMID- 9613628
TI  - First person account: a son recovered.

PMID- 9613629
TI  - After health sector reform, whither lung health?
AB  - Health sector reform, which is currently taking place in low or middle income
      countries following the implementation of structural adjustment programmes,
      advocates the use of rational measures aimed at increasing the efficiency of the
      health services. These measures are being applied unevenly. Cuts in governments'
      social budgets have had the effect of favouring the development of the private
      medical and pharmaceutical sector, rather than rationalising the choice of
      priorities. The emphasis on cost recovery in basic health services is penalising
      the poorest and most vulnerable groups. In developing countries, a managerial
      approach that does not take into account the socio-political structures of these
      countries and the priorities of health policies only serves to aggravate the
      inequalities inherent in obtaining access to health care. Under these
      circumstances, the promotion of lung health runs the risk of being forgotten or
      compromised. The persisting or worsening weaknesses of the basic health services
      do not facilitate the application of an integrated approach to respiratory
      diseases (including tuberculosis), nor the support of a minimum package of health
      activities to offer to the population. Environmental factors affecting
      respiratory health (such as smoking and air pollution) are not taken into account
      in health sector reform, even though they constitute an obvious threat and demand
      urgent, widespread action. It is a new challenge for health personnel to promote
      and guarantee lung health.

PMID- 9613630
TI  - Two-year follow-up of directly-observed intermittent regimens for smear-positive
      pulmonary tuberculosis in China.
AB  - SETTING: The tuberculosis component of the Infectious and Endemic Disease Control
      Project in the People's Republic of China is the largest single tuberculosis
      control project in the world using directly-observed therapy and standardized
      intermittent regimens. OBJECTIVE: To determine the two-year relapse and mortality
      rates following completion of treatment. DESIGN: A prospective cohort study of
      649 cases cured in this project. The 306 new and 343 retreatment cases were
      treated under field conditions with 2H3R3Z3S3/4H3R3 and 2H3R3Z3E3S3/6H3R3E3,
      respectively. Following treatment completion, two sputum samples were collected
      every six months for two years and examined for acid-fast bacilli. Causes of
      death were identified. RESULTS: The two-year relapse rates for new and
      retreatment cases were 3.3% and 5.6%, respectively. Retreatment cases with
      delayed sputum conversion had a greater risk for subsequent relapse. The two-year
      mortality rate for new and retreatment cases was 3.3% and 8.5%, respectively. The
      higher mortality rate in retreatment cases was not attributable to relapse of
      disease, but rather to non-infectious sequelae of tuberculosis. CONCLUSION: The
      use of directly-observed intermittent regimens is effective in permanently
      removing infectious tuberculosis cases from the community.

PMID- 9613631
TI  - Cohort analyses of the treatment of smear-positive pulmonary tuberculosis
      patients under programme conditions in Korea, 1983-1994.
AB  - SETTING: Cohort analyses of the results of sputum smear-positive pulmonary
      tuberculosis patients registered in health centres in Korea under programme
      conditions from 1983 to 1994. OBJECTIVE: To assess the overall treatment results
      and their annual changing trend. DESIGN: Retrospective sample surveys of the
      nationwide treatment results of registered new smear-positive and retreatment
      patients. RESULTS: The numbers of registered smear-positive pulmonary
      tuberculosis patients have decreased steadily, from over 35000 in 1983 to about
      14000 in 1994. Over 90% of health centres, and 60-80% of registered patients,
      were covered in the cohort analyses. The overall cure rate for all patients was
      56% in 1983; this improved to around 80% in the last three years of the period
      studied, owing to increased use of short-course chemotherapy. Over 5000 patients
      per year required retreatment during the first four years; this number decreased
      steadily to less than 700 in 1994, due to the reduction in initial treatment
      failures. CONCLUSION: The overall treatment results have improved significantly
      in Korea, due to the application of short-course chemotherapy.

PMID- 9613632
TI  - Outcome of patients treated for tuberculosis in Vaud County, Switzerland.
AB  - SETTING: The outcome of tuberculosis treatment is often not assessed in low
      incidence countries such as Switzerland. In economically developed countries,
      private practitioners do not have the final responsibility for ensuring the
      completion of adequate tuberculosis treatment, and public health officers have
      little or no legal means of intervening if they are not specifically requested to
      do so. Furthermore, the reluctance of private practitioners to follow official
      guidelines may be an obstacle to the implementation of a regular surveillance
      policy. OBJECTIVE: To assess the results of treatment in patients with culture
      positive pulmonary tuberculosis and to identify the risk factors for non
      adherence to treatment. DESIGN: Retrospective study of all cases notified between
      1988 and 1992 in Vaud County, and mainly treated by independent practitioners.
      RESULTS: Among 133 patients notified with culture-positive pulmonary
      tuberculosis, complete information about treatment outcome was available for 120.
      Treatment success (cure or completed adequate treatment) was observed in 84
      patients (70%), 17 died (14%) and 19 (16%) were considered as defaulters. The
      default rate was higher among immigrants, alcoholics, intravenous drug users and
      male patients. Among non-adherent patients, 4/19 (21%) relapsed within 3 years,
      compared with 3/84 (4%) among adherent patients. CONCLUSION: The outcome of
      treatment in this group of patients does not correspond to the expected
      standards: the treatment completion rate was too low, and the default rate was
      too high. Better education of medical staff and health-care workers, use of
      directly-observed treatment, and regular surveillance of treatment outcome will
      be necessary to improve the results.

PMID- 9613633
TI  - Incidence rates, clinical features, and case identification of pediatric
      tuberculosis in Alaska.
AB  - SETTING: The population of Alaska. OBJECTIVE: To determine incidence rates,
      clinical features, and source of case identification for pediatric tuberculosis
      in Alaska. DESIGN: A state-wide, population-based, retrospective analysis of all
      cases of tuberculosis among children 0 to 14 years of age reported to the Alaska
      Division of Public Health during 1987-1994. RESULTS: Seventy children with
      tuberculous disease were identified for an incidence rate of 5.8/100000/year.
      Compared to whites, Alaska Natives (relative risk [RR], 65; 95% confidence
      interval [CI], 20 to 207) and people of other races (RR, 21; 95% CI, 5.6 to 79)
      had an increased risk of tuberculosis. Clinical features did not differ by race.
      Twenty-three of 45 persons with at least one specimen collected had a positive
      culture result, including three with isoniazid-resistant strains. While most
      cases were identified through contact investigations, 23% were identified through
      required school screening. CONCLUSION: Alaska has a high rate of pediatric
      tuberculosis, with non-white race identified as a risk factor. Required school
      screening proved useful for case identification.

PMID- 9613634
TI  - Survey of knowledge, attitudes and practices for tuberculosis among general
      practitioners in Delhi, India.
AB  - SETTING: Random survey of knowledge, attitudes and practices (KAP) for
      tuberculosis among private practitioners (PPs) in Delhi, India, in 1995.
      OBJECTIVE: To investigate the KAP of private practitioners for tuberculosis in
      Delhi where the Revised National Tuberculosis Programme (RNTP) is being field
      tested. DESIGN: A pre-tested questionnaire survey was performed among 204 doctors
      attending updates/seminars on tuberculosis in various parts of Delhi. RESULTS: In
      a suspected case of tuberculosis, sputum examination was advised by only 12% of
      the PPs, while 89.5% would recommend chest X-ray. For treating tuberculosis 187
      PPs were using 102 different regimens, and only 29.4% PPs were using the regimen
      recommended by the RNTP; 51.3% PPs were over-treating their patients. Only 23.5%
      of PPs requested sputum examination before the end of treatment, while 35.5%
      depended on X-ray clearance with clinical improvement. Only 19.5% of PPs
      emphasized the importance of regular treatment for their patients. CONCLUSION:
      Among PPs there is marked reliance on X-ray; sputum examination is being
      neglected for initial diagnosis, treatment monitoring and as a criterion for
      stopping treatment. The majority of PPs are not aware of, or are not prescribing,
      the treatment regimen recommended by the RNTP, and the majority of patients are
      being over-treated. There is a lack of emphasis on proper health education. PPs
      need more training, and more collaborative efforts are required between public
      health facilities and practising doctors for national control of tuberculosis.

PMID- 9613635
TI  - Use of DNA fingerprinting for primary surveillance of nosocomial tuberculosis in
      a large urban hospital: detection of outbreaks in homeless people and migrant
      workers.
AB  - SETTING: A large urban teaching hospital in the southeast of Paris. OBJECTIVE:
      Primary surveillance of nosocomial transmission of tuberculosis (TB) by
      systematic restriction fragment length polymorphism analysis (RFLP) of isolates
      (n = 161) recovered from smear-positive pulmonary TB patients identified from 1
      March 1993 to 28 February 1994, and from all TB patients (with any form of
      tuberculous infection) identified from 1 March 1994 to 30 April 1995. RESULTS:
      Systematic RFLP analysis revealed 12 clusters of patients (n = 40) infected by
      strains of Mycobacterium tuberculosis showing matching RFLP patterns. None of the
      isolates were multidrug-resistant. Compared with non-clustered patients,
      clustered patients were more likely to be homeless (55% vs 19%, P < or = 0.001),
      or Africans living in hostels for migrant workers (20% vs 6%, P = 0.01), and had
      fewer previous admissions to hospital (12% vs 28%, P = 0.05). Further
      epidemiological investigations showed that the clustered TB cases actually
      resulted not from nosocomial transmission, but from transmission in the
      community, very likely in homeless shelters and hostels for migrant workers.
      CONCLUSION: No nosocomial transmission of TB was identified among the patients
      included during the study period. Systematic RFLP analysis using hospital-based
      sampling can detect the spread of TB in specific environments in the community
      where transmission is occurring.

PMID- 9613636
TI  - Impact of human immunodeficiency virus type-1 infection on the initial
      bacteriologic and radiographic manifestations of pulmonary tuberculosis in
      Uganda. Makerere University-Case Western Reserve University Research
      Collaboration.
AB  - SETTING: TB Treatment Centre, Kampala, Uganda. OBJECTIVE: To evaluate the impact
      of human immunodeficiency virus (HIV) co-infection on the bacteriologic and
      radiographic presentation of pulmonary tuberculosis (TB) in Uganda, a nation with
      high rates of Mycobacterium tuberculosis and HIV infection. DESIGN: To compare
      baseline characteristics among HIV-infected and non-HIV-infected adults with
      initial newly-diagnosed episodes of culture-confirmed pulmonary TB screened for
      participation in a randomized prospective TB treatment trial. RESULTS: Negative
      and paucibacillary (very scanty or scanty) sputum acid fast bacilli (AFB) smears
      were more frequent in HIV-infected patients presenting with pulmonary TB (P =
      0.007). More HIV-infected individuals also had sputum cultures that required 7-8
      weeks incubation until positivity than non-HIV-infected patients (P < 0.01).
      Lower lung field and diffuse pulmonary infiltrates were more frequent among HIV
      infected patients. Rates of atypical X-ray presentations and cavitary disease
      were comparable between HIV-seropositive and -seronegative patients; however,
      atypical disease was more frequent in HIV-infected patients with small tuberculin
      reactions or tuberculin anergy (PPD = 0 mm). CONCLUSION: HIV co-infection was
      associated with a higher frequency of negative and paucibacillary sputum AFB
      smears. The differences in the diagnostic yields of microscopy and culture
      between HIV-infected and non-HIV-infected individuals were small and do not, in
      our opinion, significantly affect the utility of these important diagnostic tests
      in developing countries. Examining more than one sputum specimen and monitoring
      cultured specimens for a full 8 weeks may assist in optimizing the diagnostic
      yield. Upper lobe infiltrates and cavitary disease are still the most frequent
      radiographic presentations of pulmonary TB in HIV-infected and non-HIV-infected
      adults in countries with a high prevalence of TB.

PMID- 9613637
TI  - Epidemiology of AIDS and tuberculosis among United States Veterans.
AB  - SETTING: US veterans. OBJECTIVE: To evaluate the frequency of the acquired immune
      deficiency syndrome (AIDS) and tuberculosis (TB) among US veterans. DESIGN:
      Analysis of statistics for 1984-1993 from the Department of Veterans Affairs and
      the Centers for Disease Control and Prevention (CDC). RESULTS: For the first time
      in the available literature the incidence of AIDS and TB per 100000 were
      calculated for US veterans receiving health care from Veterans Administration
      Medical Centers (VAMC). Among these veterans, the incidence of AIDS in 1993 was
      2.5-fold (P < 0.001) and the incidence of TB at least 1.3-fold (P < 0.001) higher
      than among the corresponding general population. The higher the incidences of
      AIDS and TB among general population of a state, the higher are the incidences of
      the diseases among veterans of this state (P < 0.001). A high correlation (r =
      0.6, P < 0.001) between AIDS and TB among veterans was found. CONCLUSION: The
      study shows that US veterans receiving health care at VAMC are a high risk group
      for both AIDS and TB, and increased preventive measures are recommended. The
      spread of AIDS and TB among veterans of a state is probably determined by the
      spread of these diseases among the general population of that state.

PMID- 9613638
TI  - Intracranial tuberculoma in Kuwait.
AB  - OBJECTIVE: To study the manifestations of intracranial tuberculoma in Kuwait and
      to provide guidelines for the diagnosis and management of intracranial
      tuberculoma in developing countries, where the disease is common and facilities
      are limited. DESIGN: Data were collected from patients with intracranial space
      occupying lesions admitted to Adan Hospital Medical Department and the
      Neurosurgery and Neuromedical Departments at Ibn-Sina Hospital, Kuwait, from
      January 1987 to December 1995. RESULTS: Intracranial tuberculomas represented
      1.4% of all cases with intracranial space-occupying lesions in these hospitals
      (13/925); 77% of the patients were males, and seizures were the most frequent
      presenting symptom. Nine patients (66.6%) responded well to medical treatment and
      four (33.3%) failed to respond. Those who responded to medical treatment showed
      remarkable improvement of the intracranial lesions within 6 weeks, and almost
      complete resolution within 12 weeks. Seven patients required surgery, three due
      to failure of medical treatment. We report a patient who needed emergency shunt
      operation, a patient with pituitary tuberculoma, and two patients whose lesions
      recurred several years after surgery. CONCLUSION: Bearing in mind the non
      specific nature of computed tomography and magnetic resonance imaging in the
      diagnosis of intracranial tuberculoma, and the lack of advanced neurosurgical
      facilities in developing countries where the disease is common, we recommend a 6
      week therapeutic test for patients with solitary or multiple enhancing
      intracranial space-occupying lesions without mass effect. Stereotactic biopsy is
      recommended in selected cases wherever facilities are available.

PMID- 9613639
TI  - Adrenal function during tuberculous infection and effects of antituberculosis
      treatment on endogenous and exogenous steroids.
AB  - SETTING: To date, few studies have been published on the frequency of adrenal
      disorder during active tuberculosis and whether rifampicin treatment has an
      adverse effect on adrenal function. OBJECTIVE: We evaluated endogenous and
      exogenous steroid metabolism in patients with active tuberculosis before and
      during treatment to observe whether the functions were affected by tuberculosis
      and rifampicin. DESIGN: Basal hormone levels and Synacthen stimulation test were
      obtained in 22 patients with active tuberculosis before and 20-30 days after
      antituberculosis treatment including rifampicin. Exogenous steroid metabolism was
      assessed by 1 mg overnight dexamethasone suppression test before and during
      antituberculosis treatment. RESULTS AND CONCLUSION: No significant differences
      were found on basal plasma cortisol or adrenocorticotropic hormone levels, but
      significant decrements were found on basal dehydroepiandrosterone sulfate (P <
      0.05) and urinary free cortisol levels (P < 0.01) before and after commencing
      antituberculosis treatment. After Synacthen stimulation, only one patient had
      insufficient increment in plasma cortisol levels. This patient was diagnosed as a
      case of Addison's disease. Although nine patients (42%) showed sufficient
      suppression of cortisol secretion on the dexamethasone test before treatment,
      none had sufficient suppression with dexamethasone after antituberculosis
      treatment. We found less mean maximum adrenal cortisol responsiveness to
      Synacthen stimulation during the course of antituberculosis treatment (P < 0.01).
      Although impairment of adrenal function is a rare condition in active
      tuberculosis, rifampicin may have a significant effect on steroid metabolism.

PMID- 9613640
TI  - Investigation of cross contamination in a Mycobacterium tuberculosis laboratory
      using IS6110 DNA fingerprinting.
AB  - SETTING: A laboratory for routine culturing of Mycobacterium tuberculosis.
      OBJECTIVE: Investigation of an episode of laboratory cross contamination using
      IS6110 restriction fragment length polymorphism (RFLP) typing. Improvement of
      laboratory protocols to prevent contaminations in the future. To stress the
      importance of 'good laboratory practice', and interaction with clinicians about
      laboratory results. DESIGN: Fingerprinting of mycobacterial isolates from 1)
      cultures suspected of being contaminated and 2) strains suspected of being the
      source of the cross-contamination. RESULTS: RFLP typing results indicated that
      clinical samples were contaminated by strains which had been processed in species
      identification procedures one day earlier in the same safety cabinet. This cross
      contamination also resulted in exceptional RFLP typing results--mixed banding
      patterns. Three patients were treated on the basis of false-positive laboratory
      results. Because the laboratory results were confusing for the clinicians, the
      treatment of one true tuberculosis patient was severely delayed. CONCLUSION:
      'Good laboratory practice' is very important to prevent cross contamination. RFLP
      typing proved to be a useful tool to trace the source of contamination.
      Interaction with clinicians receiving doubtful results is of the utmost
      importance.

PMID- 9613641
TI  - Susceptibilities of Mycobacterium malmoense determined at the growth optimum pH
      (pH 6.0).
AB  - SETTING: Pulmonary disease caused by Mycobacterium malmoense is increasing.
      Conventional in vitro antimicrobial susceptibilities correlate poorly with
      response to treatment for this organism. Radiometrically determined minimum
      inhibitory concentrations (MICs) allow quantitative susceptibility testing for
      non-tuberculous mycobacteria. The M. avium complex (MAC) has been investigated
      extensively with this approach, and clear interpretative criteria have been
      established at pH 6.8. However, there has been little work with the acidophilic
      M. malmoense, which grows poorly at pH 6.8. OBJECTIVE: To determine whether MICs
      at pH 6.0 provide results compatible with the interpretative criteria established
      for the MAC. DESIGN: MICs were performed in Middlebrook PZA medium (pH 6.0) and
      7H12 medium (pH 6.8) for ten strains of M. malmoense. RESULTS: MICs can be
      determined at pH 6.0 for M. malmoense using the criteria adopted for the M. avium
      complex. CONCLUSION: The low optimal pH of M. malmoense suits this organism for
      growth in acid conditions. As with MAC, M. malmoense multiplies within
      macrophages in vivo, and MICs determined at pH 6.0 may reflect in vivo activity.
      The combination of radiometric MIC testing at optimal growth pH and
      interpretation based on pharmacokinetic parameters may be helpful in designing
      therapeutic regimens.

PMID- 9613642
TI  - Valvular endocarditis due to Mycobacterium tuberculosis.
AB  - Granulomas due to Mycobacterium tuberculosis are rarely observed in valvular
      structures. When observed, they are associated with disseminated tuberculosis in
      immunocompromised patients. We report the first case of tuberculous valvular
      endocarditis isolated in an immunocompetent patient. The patient had severe
      mitral valve regurgitation due to a perforation of the anterior leaflet of the
      mitral valve. M. tuberculosis was cultured from the vegetations and no other
      tuberculous foci were identified. This case exemplifies the protean
      manifestations of M. tuberculosis infections.

PMID- 9613643
TI  - The sero-prevalence of HIV infection among tuberculosis patients.

PMID- 9613644
TI  - Student recruitment for TB control.

PMID- 9613645
TI  - Possible sexual transmission of genitourinary tuberculosis.

PMID- 9613646
TI  - The interruption of transmission of indigenous measles in the United States
      during 1993.
AB  - BACKGROUND: The United States has a goal to eliminate all indigenous cases of
      measles by the year 2000. Initial interruption of indigenous measles transmission
      would be expected during a period of very low measles incidence as occurred
      during late 1993. METHODS: Indigenous measles cases (i.e. cases acquired in the
      United States and not traceable to any imported case) from 1993 were investigated
      to determine their source of infection. The probability of sustained undetected
      measles transmission between isolated indigenous cases was estimated. RESULTS: Of
      the 312 measles cases reported for 1993, only 25 (8%) occurred after September
      19. Of these only 4 cases (16%) could be classified as indigenous. The estimated
      probability that any of these 4 cases resulted from indigenous measles
      transmission in theirs or any adjoining counties was 0.05 or less. CONCLUSIONS:
      Interruption of indigenous measles transmission appears to have occurred for the
      first time throughout the United States in 1993. This event provides strong
      support for the current national strategy for measles elimination. However,
      complete elimination of indigenous measles will require maintaining high
      population immunity to prevent spread from imported cases and attaining global
      measles control to prevent the importation of measles.

PMID- 9613647
TI  - Intranasally administered immunoglobulin for the prevention of rhinitis in
      children.
AB  - OBJECTIVE: To determine the efficacy of intranasally administered immunoglobulin
      in preventing symptoms of rhinitis in children. METHODS: Forty children ages 1 to
      4 years who attended day-care centers in Turku, Finland, were enrolled in the
      double blind, placebo-controlled study. The children were randomly assigned to
      receive treatment with immunoglobulin, composed mainly of immunoglobulin A, or
      placebo, both administered as nasal sprays twice daily for 8 weeks. During this
      medication period and an additional 8-week follow-up period, the parents recorded
      the symptoms of the children daily in the diaries provided. One child who met an
      exclusion criterion was withdrawn from the study after a few days of medication.
      RESULTS: During the 8-week medication period the 19 children in the
      immunoglobulin group had 42% fewer days with rhinitis than the 20 children
      receiving placebo (mean, 10.8 vs. 18.7 days; P=0.004). The total numbers of
      episodes of rhinitis in the immunoglobulin and placebo groups were 33 and 51,
      respectively. No significant differences were observed between the groups during
      the postmedication follow-up period. CONCLUSIONS: Intranasal administration of
      immunoglobulin appears to be an effective method to prevent symptoms of rhinitis
      in children, and further studies of this approach are needed.

PMID- 9613648
TI  - Risk factors for juvenile onset recurrent respiratory papillomatosis.
AB  - BACKGROUND: Children born to condylomatous mothers are at risk for developing
      juvenile onset recurrent respiratory papillomatosis (JORRP). We inquired whether
      the triad of vaginal delivery, being firstborn and maternal age of <20 years are
      also risk factors for JORRP. METHODS: Data for JORRP and adult onset recurrent
      respiratory papillomatosis cases were obtained from questionnaires answered by
      patients or their parents for the Recurrent Respiratory Papillomatosis
      Foundation. The observed numbers of cesarean births, first order births and
      births to mothers <20 years old were compared with expected numbers for the same
      variables, which were computed by distributing the cases by year of birth and
      then applying to them national annual statistics for the year of birth. In
      addition observed and expected numbers of first order births to mothers <20 years
      old were compared with corresponding numbers in mothers 20 years old or older.
      RESULTS: In JORRP cases the relationships be tween observed and expected numbers
      of cases were as follows: cesarean births, 4.6-fold less; first order births, 1.6
      fold greater; maternal age <20 years old, 2.6-fold greater. All these differences
      were statistically highly significant. The observed parity effect was mediated to
      a large extent by maternal age. In contrast there were no significant differences
      between observed and expected numbers of adult onset recurrent respiratory
      papillomatosis cases with respect to any of the above variables. CONCLUSIONS:
      Young primiparous mothers with condylomas are at a high risk for transmission of
      JORRP to their infants. The option of cesarean delivery should be discussed with
      a mother who has condyloma at the time of delivery.

PMID- 9613649
TI  - Studies of the continuing susceptibility of group A streptococcal strains to
      penicillin during eight decades.
AB  - BACKGROUND: In view of the widespread use of penicillin for >50 years for the
      treatment of group A streptococcal infections, we examined the question of
      whether there has been a change in susceptibility to penicillin in group A
      streptococcal strains collected during a span of 80 years (1917 to 1997).
      METHODS: One hundred thirty-three group A streptococcal strains collected during
      80 years were tested for changes in penicillin susceptibility. Three tests were
      used: (1) the microtiter broth minimal inhibitory concentration (MIC); (2) the
      minimal bactericidal concentration (MBC); and (3) the penicillin E strip MIC.
      RESULTS: The results indicate there has been no change in the susceptibility to
      penicillin in these group A streptococci during the past 80 years. The microtiter
      broth MIC90 for the oldest strains (0.032 microg/ml) was not significantly
      different from those collected most recently (0.032 microg/ml); there is no
      statistical difference between the raw MIC data for the four collection periods
      (P=0.468, analysis of variance on ranks). CONCLUSIONS: There has been no change
      in the susceptibility of group A streptococci during this time in spite of well
      documented cases of penicillin resistance in other Gram-positive organisms and
      despite recognized resistance of group A streptococci to other antibiotics.

PMID- 9613650
TI  - Bacteremia in febrile human immunodeficiency virus-infected children presenting
      to ambulatory care settings.
AB  - BACKGROUND: Risk factors for bacteremia in febrile HIV-infected children are
      unknown. OBJECTIVE: To describe the frequency of bacteremia in febrile HIV
      infected infants and young children in ambulatory settings and its association
      with clinical and laboratory factors. METHODS: In a birth cohort of 42 HIV
      infected children, all febrile outpatient encounters at < or = 36 months of age
      were reviewed for HIV disease severity, presence of a central venous catheter
      (CVC) and the usage of antibiotics and/or intravenous immunoglobulin (IVIG).
      Blood culture results, highest temperature and white blood cell count (WBC) were
      noted. RESULTS: There was a mean of 1.8 febrile visits (210 visits/116.5 subject
      years) per child year of observation. Rapid HIV-disease progressors (n=14) were 4
      times more likely to have a febrile visit than 28 non-rapid HIV disease
      progressors (P < 0.01). Blood cultures and WBCs were obtained for 87 and 89% of
      the febrile visits, respectively. Eleven of the 27 positive blood cultures grew
      Streptococcus pneumoniae and 16 grew CVC related organisms. The only pathogen
      identified (n=9) in 104 febrile visits in children without a CVC was S.
      pneumoniae, which was often (7 of 9) associated with mild illnesses. In children
      without a CVC temperature > or = 39 degrees C was significantly associated with
      S. pneumoniae bacteremia (P < 0.05). In 79 febrile visits by subjects with a CVC,
      temperature > or = 39 degrees C and WBC > or = 15000 cells/mm3 were frequently
      observed in the 16 bacteremic compared with the 63 nonbacteremic episodes (P < or
      = 0.05). There was a trend toward fewer S. pneumoniae bacteremias (3 of 11) in
      febrile subjects who were receiving antibiotics or IVIG. CONCLUSION: HIV-infected
      children younger than 36 months of age have a high incidence of S. pneumoniae and
      CVC-related bacteremias. Temperature > or = 39 degrees C, WBC > or = 15000
      cells/mm3 and the presence of a CVC should be considered in the management of
      febrile HIV-infected children.

PMID- 9613651
TI  - Shedding of rotavirus after administration of the tetravalent rhesus rotavirus
      vaccine.
AB  - BACKGROUND: The tetravalent rhesus rotavirus vaccine (RV-TV) has been
      administered to several thousand children in multiple settings throughout the
      world. It has been proved safe and efficacious, resulting in an application for
      licensure in 1997. However, only limited information has been reported on viral
      shedding after RV-TV vaccination. METHODS: Stool specimens were collected between
      Days 3 and 5 after administration of each of 3 doses of RV-TV to 248 subjects 6
      to 12 weeks of age in 8 centers across the United States. Rotavirus antigen was
      measured by an enzyme-linked immunosorbent assay to determine the number of
      subjects who shed after each dose. The relative quantities of vaccine strains
      shed were then determined by plaque purification and serotype analysis. RESULTS:
      Rotavirus shedding was detected in 125 (50.4%) subjects, and 19 shed after more
      than 1 dose. Although fewer subjects shed rotavirus after Dose 2 (14.5%),
      shedding after Doses 1 (26.0%) and 3 (22.5%) were comparable. After plaque
      purification and serotyping, most viruses shed (76.2%) were identified as G3
      after Dose 1, but a major shift to G2 strains was found after Doses 2 (61.3%) and
      3 (69.0%). CONCLUSIONS: Sequential RV-TV administrations caused no overall
      significant decrease in the number of vaccinees who experienced detectable
      shedding. A major shift in shedding was found from the serotype G3 vaccine strain
      (RRV) after the first dose of vaccine to the serotype G2 reassortant after Doses
      2 and 3.

PMID- 9613652
TI  - The immunogenicity of Haemophilus influenzae type b conjugate vaccines in
      children born to human immunodeficiency virus-infected women. Women and Infants
      Transmission Study Group.
AB  - BACKGROUND: Immunocompromise caused by HIV-1 infection increases the importance
      of receipt of routine childhood vaccines to prevent infections such as invasive
      Haemophilus influenzae type B (Hib) disease. The objectives of the study were to
      evaluate the immunogenicity of Hib conjugate vaccines among HIV-infected children
      according to clinical and immunologic disease progression as well as viral load.
      METHODS: The concentration of antibody to polyribosylribitol phosphate (PRP) was
      measured at approximately 9 and 24 months of age in plasma specimens from
      children of HIV-infected women enrolled in the Women and Infants Transmission
      Study. RESULTS: Among 227 children (35 HIV-infected, 192 uninfected) at the 9
      month study visit who were known to have received age-appropriate immunization
      with CRM197 mutant Corynebacterium diphtheriae protein-conjugated Hib vaccine,
      geometric mean antibody concentrations were lower among HIV-infected children
      (1.64 microg/ml) than among uninfected children (2.70 microg/ml), although the
      difference was not statistically significant. Anti-PRP antibody concentrations
      did not vary significantly among these HIV-infected children with predominantly
      mild-moderate disease progression according to clinical category, immunologic
      stage or viral load (P > or = 0.48). The proportion of children with antibody
      concentrations > or = 1.0 microg/ml did not vary significantly according to HIV
      infection status (73% uninfected, 74% infected) or, if infected, clinical or
      immunologic disease progression or viral load. Similar results were obtained
      among 127 children (17 HIV-infected, 110 uninfected) eligible for analysis at the
      24-month study visit. Changes in antibody concentrations over time (between 9 and
      24 months of age) did not differ significantly among 10 HIV-infected as compared
      with 72 uninfected children (P=0.81). CONCLUSIONS: These results suggest that HIV
      infected children with predominantly mild-moderate disease progression respond
      reasonably well in terms of a quantitative antibody response to Hib conjugate
      vaccines during the first 2 years of life. Research to further characterize the
      immune response to Hib conjugate vaccines and to further delineate the
      "durability" of anti-PRP antibody concentrations beyond 2 years of life should be
      pursued.

PMID- 9613653
TI  - Pneumocystis carinii pneumonia prophylaxis and early clinical manifestations of
      severe perinatal human immunodeficiency virus type 1 infection. Northern
      California Pediatric HIV Consortium.
AB  - BACKGROUND: Some children with perinatal HIV infection develop early progression
      to severe symptoms (Category C) within the first 4 years of life. Prophylactic
      therapy with trimethoprim-sulfamethoxazole (TMP/SMX) may affect progression by
      decreasing the incidence of Pneumocystis carinii pneumonia (PCP). METHODS: HIV
      progression to Category C in the first 3 years of life was retrospectively
      analyzed in a population-based cohort of children with perinatal HIV infection
      followed for > or = 3 years from birth. Time to development of Category C and
      clinical patterns of new Category C diagnoses were examined in relation to
      patterns of PCP prophylaxis before diagnosis. RESULTS: Fifty-eight of 147
      children developed 67 initial category C diseases by 3 years of age: PCP (n=24),
      encephalopathy (n=22), other opportunistic infections (n=19) and wasting (n=2).
      Before diagnosis therapy included TMP/ SMX and zidovudine (ZDV) (n=11), TMP/SMX
      alone (n=7), ZDV alone (n=1) and neither (n= 39). The probability of developing a
      Category C diagnosis after 2 years was significantly lower among children who
      received TMP/SMX compared with those who did not (29%, TMP/SMX vs. 45%, no
      TMP/SMX; 30%, TMP and ZDV vs. 45%, no therapy; P < 0.01). The frequency of PCP
      was significantly lower and that of HIV encephalopathy was significantly higher
      among children receiving TMP/SMX +/- ZDV before Category C diagnosis than among
      children receiving neither. CONCLUSION: In this study PCP prophylaxis was
      associated with longer time to Category C diagnoses in the first 3 years of life.
      This association was related to a decreased incidence of PCP and an increased
      incidence of encephalopathy as the first Category C diagnosis among children who
      received TMP/SMX.

PMID- 9613654
TI  - Management of children with tuberculosis admitted to a pediatric intensive care
      unit.
AB  - OBJECTIVES: To review the incidence, clinical features, ventilatory support and
      outcome of children with tuberculosis (TB) admitted to a Pediatric Intensive Care
      Unit (PICU) in a region with an high incidence of TB. MATERIALS AND METHODS: The
      study was performed in a PICU situated in a province with a extremely high
      incidence of TB (> 700 new cases/ 100000/year). This is a retrospective
      descriptive study of TB admissions to the PICU in a 4-year period. Data regarding
      indications for admission, clinical picture, duration of ventilation, PICU and
      hospital stay were collected from patient files. Outcome measures included
      mortality and long term morbidity. RESULTS: Of the 1862 children admitted to the
      hospital for TB during the 4 years, 57 (3.1%) required PICU admission (1 to 6% of
      annual admissions). Of these 57 children 41 (72%) were admitted for respiratory
      failure. In 12 cases TB was the cause of the respiratory failure, 17 cases
      suffered from other respiratory diseases and in 12 cases the cause was
      nonrespiratory disease of which TB meningitis (n=8) was the most common.
      Mechanical ventilation was indicated in 43 (75%) patients who were ventilated for
      7.3+/-11.5 days. The duration of PICU admission was 10.2+/-2.4 days whereas the
      duration of hospitalization was 70.3+/-148.9 days. The PICU mortality was 23%
      with TB meningitis having the highest mortality of 75%. CONCLUSIONS: In a region
      with a high incidence of TB, tuberculous patients constitute up to 6% of PICU
      admissions. A high degree of suspicion for the diagnosis is needed because in 30%
      of our cases the diagnosis was not initially considered.

PMID- 9613655
TI  - Tuberculosis in children and adolescents: California, 1985 to 1995.
AB  - OBJECTIVES: To describe the epidemiology and clinical characteristics of
      tuberculosis (TB) among children and adolescents and to define children at risk
      for TB. SETTING: 4607 children 0 to 14 years of age and 1615 adolescents 15 to 19
      years of age reported with TB in California. METHODS: We analyzed surveillance
      data reported to the California Department of Health Services TB Control Branch
      from 1985 through 1995. RESULTS: TB cases increased 22% among children 0 to 4
      years of age and 66% among children 5 to 14 from 1985 through 1995. Case rates
      were highest among children 0 to 4 years of age (13/ 100000 children), but
      declined from 1993 to 1995, except for black children 0 to 4 years of age.
      Minority children 0 to 14 years of age had case rates 6- to 34-fold higher than
      did white children. Pulmonary TB was the most common site of disease in all age
      groups (71 to 82%). TB meningitis was most common in children 0 to 4 years of age
      (5%). Most children (64%) did not have cultures done; however, among culture
      proved cases isoniazid-resistant Mycobacterium tuberculosis was isolated in 7%.
      Adolescents were more likely to have cavitary pulmonary disease (24%), to be
      foreign-born (78%) or homeless (4%) and to have an isoniazid-resistant strain
      isolated (13%) than were children 0 to 14 years of age (P < 0.05). CONCLUSIONS:
      TB in children and adolescents increased substantially in the mid-1980s and early
      1990s. Pediatric TB remains a serious health problem, especially among minority
      children and adolescents. Our findings indicate that TB control programs need
      improved strategies to prevent infection and detect disease in this population.

PMID- 9613656
TI  - Epidemiology of pertussis in French hospitals in 1993 and 1994: thirty years
      after a routine use of vaccination.
AB  - BACKGROUND: Despite widespread vaccination during 30 years, the hypothesis of a
      resurgence of pertussis in France has been raised by outbreaks and sporadic case
      reports. No surveillance data were available after 1985. METHODS: A survey was
      undertaken in 1993 and 1994 in a pediatric hospital network able to confirm
      cases; the network (22 hospitals) represents 19.6% of pediatric admissions in
      France. Case definition included clinical (> or = 21 days of paroxysmal cough),
      laboratory-confirmed (culture or serology by immunoblot) or epidemiologically
      confirmed pertussis (documented contact with a laboratory-confirmed case). The
      pattern of transmission was studied in the household. Vaccine status was obtained
      from health records. RESULTS: during a 15-month period 560 cases (316 index
      cases, 244 household contact cases) were reported; 49% of index cases and 20% of
      contact cases were confirmed by culture and/or serology. Sixty-five percent of
      index cases were younger than 1 year of age (the incidence in this age group
      could be estimated to be 95/100000) and 66% were hospitalized for a mean duration
      of 2 weeks. Infection was acquired from parents (34%) and siblings (46%). Seventy
      three percent of index cases were unvaccinated. CONCLUSIONS: Although pertussis
      vaccination coverage is very high in France, the organism is still circulating,
      affecting, within the pediatric population, mostly non- or incompletely
      vaccinated infants. These results strongly support the importance of adhering to
      the immunization schedule and suggest introducing booster dose(s) to prolong
      vaccine immunity and reduce the exposure to Bordetella pertussis of infants too
      young to be immunized.

PMID- 9613657
TI  - Treatment of head lice.

PMID- 9613658
TI  - Treatment of bacterial enteritis.

PMID- 9613659
TI  - AmpC beta-lactamases.

PMID- 9613660
TI  - Borrelia lymphocytoma in childhood.

PMID- 9613661
TI  - Prolonged efficacy of rhesus-human reassortant rotavirus vaccine.

PMID- 9613662
TI  - Doxycycline and staining of permanent teeth.

PMID- 9613663
TI  - Elevated gamma-glutamyltransferase concentrations in patients with acute Kawasaki
      disease.

PMID- 9613664
TI  - Reversible parkinsonism in a child after bone marrow transplantation and lipid
      based amphotericin B therapy.

PMID- 9613665
TI  - Profound anemia in a newborn infant of a mother receiving antiretroviral therapy.

PMID- 9613666
TI  - Leptospirosis and pancreatitis: a report of ten cases.

PMID- 9613667
TI  - Salmonella bacteremia after intestinal injury.

PMID- 9613668
TI  - Tularemic meningitis.

PMID- 9613669
TI  - Abdominal and leg pain in a twenty-three-month-old child.

PMID- 9613670
TI  - Fungemia in children with neoplastic diseases.

PMID- 9613671
TI  - Recurrent Francisella philomiragia sepsis in chronic granulomatous disease.

PMID- 9613672
TI  - The FLT3/FLK2 ligand: structure, functions and prospects.

PMID- 9613673
TI  - Fifth annual conference of the International Cytokine Society. State of the art.

PMID- 9613674
TI  - Molecular mechanisms of fever: the missing links.

PMID- 9613675
TI  - Correlation of serum levels of interleukin-1 family members with disease activity
      and response to treatment in hairy cell leukemia.
AB  - Hairy cell leukemia (HCL) is a well-recognized chronic lymphoproliferative
      disorder of B cell lineage, which may be regulated by growth factors including
      cytokines and cytokine antagonists. Previous studies have shown a good
      correlation between circulating soluble interleukin-2 receptor (sIL-2R) levels
      and disease activity and response to therapy was always associated with a
      decrease in sIL-2R levels. The interleukin-1 (IL-1) family of agonists and
      antagonists may also be involved in the regulation of hematopoietic malignancies.
      In the present study, we evaluated members of the IL-1 family (IL-1beta, IL-1
      receptor antagonist (IL-1Ra) and IL-1 soluble receptors Type I and Type II (IL
      1sRI and IL-1sRII) in 23 patients with HCL. Patients were classified according to
      the clinical state of their disease. Most were treated with 2-chloro-2'
      deoxyadercosine (2-CDA) and treatment was associated with a significant decrease
      in the serum levels of sIL-2R, IL-1beta and IL-1sRII in patients achieving a
      complete or partial response. In contrast to the above, levels of IL-1Ra
      increased during response to treatment and clinical response to 2-CDA was
      associated with an increase of 122% in IL-1Ra levels, in parallel with a decrease
      of 63% in IL-1beta and 47% in IL-1sRII levels. These results suggest that the
      balance between IL-1beta, IL-2 and their soluble receptors or antagonists may be
      involved in the pathogenesis and immunoregulation of HCL. Serum levels of these
      cytokines may therefore be used to monitor therapeutic efficacy of therapy in HCL
      and to detect any residual disease.

PMID- 9613676
TI  - Biological activity of human epidermal interleukin-1beta: comparison with
      recombinant human interleukin-1beta.
AB  - We have recently presented evidence that human plantar stratum corneum and
      psoriatic scales contain biologically active interleukin-1beta (IL-1beta) which
      has been activated in a process not involving interleukin-1beta-converting
      enzyme. The aim of the present study was to compare this form of native IL-1beta
      with recombinant mature human IL-1beta as regards activity and the effects of
      inhibitors. In an assay based on the ability of IL-1 to induce the expression of
      E-selectin in cultured endothelial cells, the maximal activity of IL-1beta
      partially purified from plantar stratum corneum and recombinant IL-1beta was
      approximately the same. The specific activity was slightly higher for recombinant
      IL-1beta, although this difference was within one order of magnitude. An antibody
      to IL-1beta caused total inhibition of both forms of IL-1beta with no significant
      differences in the dose-response curves for the antibody. Immunochemical analyses
      and experiments with neutralising antibodies specific for IL-1alpha and tumor
      necrosis factor-alpha (TNF-alpha) verified that the observed activity in the
      partially purified preparation was due to IL-1beta, and not to IL-1alpha or TNF
      alpha. There were no significant differences between the two forms of IL-1beta as
      regards the inhibitory effects of recombinant IL-1 receptor antagonist. Partially
      purified IL-1beta from plantar stratum corneum and from psoriatic scales were
      both highly active in the D10 proliferation assay. This activity could be totally
      inhibited with an IL-1beta specific antibody. This work thus confirms the
      presence of biologically active IL-1beta in plantar stratum corneum and psoriatic
      scales. Alternatively activated IL-1beta in the epidermis should be considered in
      future studies on skin biology and pathophysiology.

PMID- 9613677
TI  - Interleukin-8 and monocyte chemotactic protein-1 production by a human
      glioblastoma cell line, T98G in coculture with monocytes: involvement of monocyte
      derived interleukin-1alpha.
AB  - We have previously demonstrated that a human glioblastoma cell line, T98G cells,
      produced high levels of interleukin-8 (IL-8) and monocyte chemotactic protein-1
      (MCP-1) when stimulated with IL-1 or tumor necrosis factor-alpha (TNF-alpha). In
      this study, we found that T98G cells are capable of producing large amounts of IL
      8 and MCP-1 when cocultured with human peripheral blood monocytes or a monocytic
      cell line, U937 cells. Since it is possible that both glioblastoma cells and
      monocytes are capable of producing chemokines, we determined which type of cells
      actually produced IL-8 and MCP-1, by the fixation of one or the other cell type
      with 3% paraformaldehyde (PA). This procedure revealed that T98G cells were the
      main source and that PA-treated monocytes effectively stimulated IL-8 and MCP-1
      production by T98G cells. Both IL-8 and MCP-1 gene expression and protein
      production by T98G cells were confirmed by northern blot as well as
      immunohistochemical staining methods. To analyze the molecules on human monocytes
      responsible for inducing IL-8 and MCP-1 by T98G cells, several antibodies (Abs)
      as well as IL-1 receptor antagonist (IL-1Ra) were tested. Anti-IL-1alpha Ab and
      IL-1Ra almost completely abolished the IL-8/MCP-1-inducing capacity of the PA
      fixed monocytes, while no inhibition was obtained with anti-IL-1beta, anti-TNF
      alpha or Abs against CD11b/18, L-selectin or ICAM-1, indicating that membrane
      associated IL-1alpha is involved in the IL-8/MCP-1 induction, while secreted IL
      1alpha plays a major role in this cell-to-cell, i.e., juxtacrine interaction in
      unfixed conditions.

PMID- 9613678
TI  - Inflammation: "a natural experiment" for the systemic pathogenicity of cytokines.
AB  - It has previously been demonstrated that the overproduction of interleukin-6 (IL
      6) is a key element in the clinical and biological abnormalities encountered in
      Castleman's disease (CD). The particular case of a male child with a localized
      form of CD is reported. In this patient, evidence was found of a correlation
      between systemic manifestations and circulating IL-6, and IL-6 gene
      overexpression in the germinal centers of hyperplastic lymph nodes. Circulating
      IL-6 levels were 10- to 100-fold higher than in all CD cases previously
      documented. This unique biological feature was closely associated with high
      levels of circulating IL-1 and tumor necrosis factor-alpha (TNF-alpha), which are
      known for their ability to induce and/or amplify IL-6 production. One month after
      surgical removal of the pathological lymph node, the clinical and biological
      abnormalities diminished, while circulating IL-6 levels dropped dramatically
      eight months later. It is worth noting that after resection, the time-course of
      the IL-6 decrease closely correlated with that of IL-1 and TNF-alpha. Considering
      that in various inflammatory diseases IL-1, TNF-alpha and IL-6 may act in a
      synergistic manner in inducing systemic manifestations, this case report raises
      new questions as to the nature of the systemic pathogenicity of cytokines in CD.

PMID- 9613679
TI  - Local release of interleukin-10 by transfected mouse adenocarcinoma cells
      exhibits pro- and anti-inflammatory activity and results in a delayed tumor
      rejection.
AB  - Tumor cells engineered to release cytokines are a valuable tool for investigating
      biological activities elicited by local cytokines. The parental cells of a mouse
      mammary adenocarcinoma (TSA-pc) were transduced with the cDNA coding for mouse
      interleukin-10 (IL-10). In vitro, transduced TSA cells secrete about 200 ng of IL
      10/10(5) seeded cells in 48 hours (TSA-IL-10). When injected subcutaneously into
      syngeneic BALB/c mice, TSA-IL-10 cells gave rise to a tumor that grew
      progressively during the first 7-10 days and then rapidly and completely
      regressed. To study the events associated with this growth and disappearance,
      histological, immunohistochemical and ultrastructural analyses of the tumor area
      were performed at progressive times after challenge. A slow, but progressive and
      massive recruitment of leukocytes (mainly macrophages and neutrophils) into the
      tumor was evident. Several CD8+, CD4+ lymphocytes and a few NK cells were
      present. Marked inhibition of neoangiogenesis was also observed. On day 9, the
      microvascular network in the growth area had almost vanished, while vascular
      damage was present in the surrounding stromal tissue. From day 4, down-modulation
      of VEGF expression in the tumor area and inhibition of tumor necrosis factor
      alpha (TNF-alpha) and IL-6 production by reactive leukocytes were evident. The
      few vessels present in the tumor area displayed poor expression of monocyte
      chemotactic protein-1 (MCP-1), moderate expression of VCAM-1, and strong
      expression of ELAM-1, three molecules that result in adhesion of inflammatory
      cells to the endothelium. A few tumor-infiltrating macrophages were moderately
      stained with anti-iNOS antibodies. These findings suggest that the collapse of
      established TSA-IL-10 tumors is the result of the pro- and anti-inflammatory
      activity of IL-10, which: a) is a signal for the local recruitment of leukocytes;
      b) leads to vascular damage; c) suppresses cytokine production. The coexistence
      of both a direct stimulatory activity on endothelial cells and an anti-angiogenic
      activity is evidence of the ambivalence of the local effects of IL-10.

PMID- 9613680
TI  - Molecular cloning and sequencing of the rat interleukin-12 p40 gene.
AB  - The nucleotide sequences containing the rat interleukin-12 p40 gene was
      determined. Sequencing revealed the presence of six exons and five introns.
      Analysis of the 5' non-coding region showed the presence of several possible
      sites involved in cytokine gene regulation at the transcriptional level.
      Comparison of the deduced amino acid sequence of rat IL-12 p40 with that of the
      mouse and of human p40, showed 92% and 65% identity respectively.

PMID- 9613681
TI  - Differential mRNA expression and production of interleukin-4 and interferon-gamma
      in stimulated peripheral blood mononuclear cells of house-dust mite-allergic
      patients.
AB  - Optimal culture conditions were established for the analysis of interleukin-4 (IL
      4) and interferon-gamma (IFN-gamma) mRNA expression and protein production, as
      well as proliferative capacity of peripheral blood mononuclear cells (PBMC).
      These culture conditions permitted the analysis of differences in the responses
      of house-dust mite (HDM) allergic patients and healthy controls after polyclonal
      and allergen-specific stimulation. Proliferative responses were optimal when PBMC
      were cultured in RPMI, whereas for studying mRNA expression by RT-PCR and protein
      production by ELISA, PBMC should be stimulated in Yssels's medium. Blood holding
      period influenced the cytokine mRNA expression and proliferative capacity of
      primarily the unstimulated cells. It is thus crucial to isolate PBMC as soon as
      possible, and in any event no later than 7 hours after blood collection.
      Proliferative responses to Dermatophagoides pteronyssinus-extract were observed
      in HDM allergic patients (mean stimulation index (SI) = 5.3+/-0.75), but not in
      non-allergic subjects (mean SI = 2.3+/-0.21). After D. pteronyssinus-specific
      stimulation, IL-4 mRNA expression was significantly (p = 0.03) increased in HDM
      allergic subjects compared to non-allergic subjects. No significant differences
      were found in IFN-gamma mRNA expression between HDM-allergic and non-allergic
      subjects. Both IFN-gamma (p = 0.04) and IL-4 (p = 0.06) protein production were
      increased after D. pteronyssinus-specific stimulation in HDM-allergic subjects
      compared to non-allergic subjects. Our data suggest activation of both Th1 and
      Th2-like cells, as well as CD8+ T cells in allergic patients. Furthermore,
      analysis of possible functional differences in PBMC between allergic and non
      allergic patients, necessitates polyclonal and allergen-specific stimulation of
      PBMC. Moreover, proliferative responses as well as cytokine mRNA expression and
      protein production should be studied under optimal culture conditions to
      highlight the often subtle differences.

PMID- 9613682
TI  - Stem cell factor-deficient mice have a dysregulation of cytokine production
      during local inflammation.
AB  - We have studied the responses of stem cell factor-deficient (SCF-) mice in two
      models of local inflammation, turpentine-induced tissue damage and zymosan
      induced peritonitis. These mice have a profound mast cells deficiency. Following
      administration of either zymosan or turpentine, SCF- mice developed a more severe
      body weight loss than wild type (SCF+) mice. An exaggerated systemic production
      of interleukin-1beta (IL-1beta) and IL-6 was observed in SCF- mice. However,
      systemic tumor necrosis factor-alpha (TNF-alpha) levels were undetectable in SCF-
      mice following zymosan administration. The peritoneal lavage fluid (PLF) of SCF-
      mice also showed a marked increase in IL-1beta following zymosan administration,
      whereas local IL-6 and TNF-alpha production were not affected. In addition, PLF
      levels for the chemokine MIP-1alpha were strongly reduced in SCF- mice. This was
      associated with a reduced number of infiltrating cells. A possible mechanism for
      these differences was a reduction in IL-4 production in SCF- mice. Both local and
      systemic levels for IL-4 were significantly lower in SCF- mice following either
      zymosan or turpentine administration. Our results suggest that mast cells and/or
      SCF are important regulators of the production of cytokines in the course of
      inflammatory responses.

PMID- 9613683
TI  - Benefits of granulocyte-colony-stimulating factor after stem cell transfusion in
      intensive sequential chemotherapy for breast cancer.
AB  - The aim of this study was to evaluate the clinical and economic benefit of
      filgrastim given with intensive sequential chemotherapy. Women with poor
      prognosis breast cancer received four cycles of high-dose cyclophosphamide (3
      g/m2) and doxorubicin (75 mg/m2), followed by filgrastim 5 microg/kg/dy, stem
      cell collection after the cycle 1, and stem cell infusion after cycle 3 and cycle
      4. The first cohort received filgrastim after the fourth cycle but the second
      cohort did not.Thirty three patients were included in the first cohort and 13 in
      the second. The results indicate that the duration of grade IV neutropenia was
      shorter in the group given filgrastim as was the median time to recover an
      absolute neutrophil count (ANC) > 1.0 x 10(9)/L. The rate and duration of the
      rehospitalizations were higher in the group not receiving filgrastim. We found
      that costs such as drugs and hospitalizations were significantly higher (p =
      0.032 and p = 0.049) in the non-filgrastim-treated group. Using ANC > 1.0 x
      10(9)/L as an intermediary efficiency criterion it was more cost effective to
      give filgrastim. It can be concluded from this study that filgrastim can decrease
      the duration of grade IV neutropenia in patients receiving intensive sequential
      chemotherapy. This, in turn, reduces the cost of hospitalization. However, in our
      study, this reduction of neutropenia did not have any impact on further therapy.

PMID- 9613684
TI  - Arg777 plays a major role in the conformation of the colony-stimulating factor-1
      receptor intracellular kinase domain.
AB  - A point mutation substituting Arg777 by Gln was obtained in a highly conserved
      region of the human colony-stimulating factor-1 receptor (CSF-1R) sequence.
      Constitutive expression of wild-type receptors in CHO cells confers
      susceptibility to CSF-1 for proliferation whereas the mutated receptors exhibited
      a 90% reduced efficiency in proliferation. We sought to determine the alterations
      intervening in the CSF-1 signal transduction of the Arg777Gln mutated receptor.
      We found that ligand binding and ligand-induced CSF-1R internalization were
      unaffected. CSF-1-induced receptor dimerization and autophosphorylation were
      impaired to the same extent as mitogen-activated protein kinase activation (90%).
      However, only phosphatidylinositol 3-kinase activation and ligand-induced
      receptor ubiquitination were abrogated by the mutation. These features probably
      reflect the inability of the mutated CSF-1R kinase domain to fold properly and
      hence to autophosphorylate and/or to associate correctly with transduction
      proteins. These data may indicate a role for the conserved regions of the RTK
      kinase domains in the stabilization of the intracellular domain conformation.

PMID- 9613685
TI  - Salmonella senftenberg outbreak.

PMID- 9613686
TI  - The stethoscope as a potential source of transmission of bacteria.

PMID- 9613687
TI  - Safety butterfly needles for blood drawing.

PMID- 9613688
TI  - Vancomycin use and monitoring in pediatric patients in a community hospital.

PMID- 9613689
TI  - Xenotransplantation: Is the future upon us?

PMID- 9613690
TI  - Accuracy of reporting nosocomial infections in intensive-care-unit patients to
      the National Nosocomial Infections Surveillance System: a pilot study.
AB  - OBJECTIVE: To assess the accuracy of nosocomial infections data reported on
      patients in the intensive-care unit by nine hospitals participating in the
      National Nosocomial Infections Surveillance (NNIS) System. DESIGN: A pilot study
      was done in two phases to review the charts of selected intensive-care-unit
      patients who had nosocomial infections reported to the NNIS System. The charts of
      selected high- and low-risk patients in the same cohort who had no infections
      reported to the NNIS System also were included. In phase I, trained data
      collectors reviewed a sample of charts for nosocomial infections. Retrospectively
      detected infections that matched with previously reported infections were deemed
      to be true infections. In phase II, two Centers for Disease Control and
      Prevention (CDC) epidemiologists reexamined a sample of charts for which a
      discrepancy existed. Each sampled infection either was confirmed or disallowed by
      the epidemiologists. Confirmed infections also were deemed to be true infections.
      True infections from both phases were used to estimate the accuracy of reported
      NNIS data by calculating the predictive value positive, sensitivity, and
      specificity at each major infection site and the "other sites." RESULTS: The data
      collectors examined a total of 1,136 patients' charts in phase I. Among these
      charts were 611 infections that the study hospitals had reported to the CDC. The
      data collectors retrospectively matched 474 (78%) of the prospectively identified
      infections, but also detected 790 infections that were not reported
      prospectively. Phase II focused on the discrepant infections: the 137 infections
      that were identified prospectively and reported but not detected retrospectively,
      and the 790 infections that were detected retrospectively but not reported
      previously. The CDC epidemiologists examined a sample of 113 of the discrepant
      reported infections and 369 of the discrepant detected infections, and estimated
      that 37% of all discrepant reported infections and 43% of all discrepant detected
      infections were true infections. The predictive value positive for reported
      bloodstream infections, pneumonia, surgical-site infection, urinary tract
      infection, and other sites was 87%, 89%, 72%, 92%, and 80%, respectively; the
      sensitivity was 85%, 68%, 67%, 59%, and 30%, respectively; and the specificity
      was 98.3%, 97.8%, 97.7%, 98.7%, and 98.6%, respectively. CONCLUSIONS: When the
      NNIS hospitals in the study reported a nosocomial infection, the infection most
      likely was a true infection, and they infrequently reported conditions that were
      not infections. The hospitals also identified and reported most of the nosocomial
      infections that occurred in the patients they monitored, but accuracy varied by
      infection site. Primary bloodstream infection was the most accurately identified
      and reported site. Measures that will be taken to improve the quality of the
      infection data reported to the NNIS System include reviewing the criteria for
      definitions of infections and other data fields, enhancing communication between
      the CDC and NNIS hospitals, and improving the training of surveillance personnel
      in NNIS hospitals.

PMID- 9613691
TI  - Use of antibiotic exposure to detect postoperative infections.
AB  - OBJECTIVE: To assess the utility of postoperative antibiotic exposure as an
      indicator of postoperative infection after coronary artery bypass graft surgery.
      DESIGN: We determined an optimal antibiotic exposure threshold by creating
      receiver operating characteristic curves. SETTING: Tertiary healthcare
      institution (United States); national sample (Israel). PATIENTS: 5,887 patients
      undergoing coronary artery bypass graft surgery. RESULTS: Postoperative
      antibiotic exposure with at least 9 days between the first and last dates of
      antibiotic administration, excluding the first postoperative day, had a
      sensitivity of 95% (261/276) and specificity of 85% (3,944/4,628) for identifying
      surgical-site infection, using as a gold standard surgical-site infections
      identified by conventional prospective surveillance or extrapolated from review
      of a sample of medical records. In contrast, using the same gold standard for
      surgical-site infections, the sensitivity of routine prospective surveillance
      alone was only 60%. The predictive value positive of the defined antibiotic
      exposure was 28% (261/945) for surgical-site infection and 60% (563/945) for any
      nosocomial infection. In the Israeli cohort, the sensitivity was 87% (74/85) and
      the specificity was 82% (735/898). CONCLUSION: Antibiotic exposure of sufficient
      duration and timing was more sensitive than conventional methods in detecting
      nosocomial infection and required substantially less effort to collect. Although
      the predictive value positive for surgical-site infection was only moderate, the
      majority of individuals identified this way had a nosocomial infection.

PMID- 9613692
TI  - Stability and bactericidal activity of chlorine solutions.
AB  - OBJECTIVES: To determine the stability of sodium hypochlorite (diluted household
      bleach) when stored for 30 days in various types of containers and to determine
      the efficacy of low concentrations of free available chlorine to inactivate test
      bacteria. DESIGN: Laboratory-based study. Solutions of standard household bleach
      were prepared using tap water or sterile distilled water at dilutions of 1:100,
      1:50, and 1:5. Chlorine concentrations were measured, and then the solutions were
      placed into five polyethylene containers and left at room temperature (20 degrees
      C) under various conditions (translucent containers with light exposure and with
      or without air; brown opaque container without light or air exposure). Samples
      for chlorine and pH determinations were taken at time 0 and on days 7, 14, 21,
      30, and 40. Bactericidal activity of chlorine solutions was assessed using the
      Association of Official Analytical Chemists Use-Dilution Method. Test bacteria
      included Pseudomonas aeruginosa, Staphylococcus aureus, and Salmonella
      choleraesuis. RESULTS: Chlorine concentrations at 30 days varied from the 40% to
      50% range for 1:50 or 1:100 dilutions stored in containers other than closed
      brown containers to 83% to 85% for the 1:5 dilution stored in closed but non
      opaque containers to 97% to 100% for 1:50 or 1:5 solutions stored in closed brown
      containers. The lowest concentration of sodium hypochlorite solution that
      reliably inactivated all the test organisms was 100 ppm. CONCLUSIONS: These data
      suggest that chlorine solutions do not need to be prepared fresh daily, as is
      recommended currently, and the lowest concentration of chlorine that reliably
      inactivates S aureus, S choleraesuis, and P aeruginosa is 100 ppm.

PMID- 9613693
TI  - Staphylococcus aureus nasal colonization in patients with cirrhosis: prospective
      assessment of association with infection.
AB  - OBJECTIVE: To determine if Staphylococcus aureus colonization of the anterior
      nares was a risk factor for S aureus infection in patients with cirrhosis and to
      determine the predictors of S aureus infection in colonized patients. DESIGN:
      Prospective cohort study. PATIENTS: 84 consecutive patients with cirrhosis
      admitted to the liver transplant unit of a university-affiliated Veterans'
      Affairs Medical Center. RESULTS: Overall, 39 (46%) of the 84 patients were nasal
      carriers of S aureus, of which 24 (29%) were methicillin-resistant Staphylococcus
      aureus (MRSA) and 15 (18%) were methicillin-sensitive Staphylococcus aureus
      (MSSA). Only MRSA, but never MSSA, carriage was acquired in the hospital; all 15
      of the MSSA versus 14 (58%) of the 24 MRSA carriers were nasal carriers on first
      (admission) culture (P=.001). Of the 10 (42%) of 24 MRSA carriers who were not
      colonized on admission, 3 became MRSA carriers within 1 month, and 7 acquired
      MRSA carriage more than a month later. Higher Child-Pugh score was independently
      associated with MRSA carriage (odds ratio [OR], 1.54; 95% confidence interval
      [CI95], 1.1-2.3). S aureus nasal carriers (9 [23%] of 39) were significantly more
      likely to develop S aureus infections than noncarriers (2 [4%] of 45; P=.02).
      Central venous catheter use was associated independently with S aureus infections
      in the carriers (OR, 4.1; CI95 2.8-6.1). Mortality was significantly higher in
      carriers who developed S aureus infections as compared to those who did not (57%
      vs 13%; P=.022); S aureus infection was an independent predictor of mortality in
      the carriers (OR, 8.7; CI95, 1.2-63.8). CONCLUSIONS: Colonization of the anterior
      nares was a significant predictor of S aureus infection in patients with
      cirrhosis.

PMID- 9613694
TI  - Reduction in vancomycin-resistant Enterococcus and Clostridium difficile
      infections following change to tympanic thermometers.
AB  - OBJECTIVE: To contain a nosocomial outbreak of vancomycin-resistant Enterococcus
      (VRE). DESIGN: Intervention study, with comparison of incidence rates before and
      after intervention to assess whether changes in incidence followed the
      intervention and were greater than expected based on trends observed before the
      intervention. SETTING: A 343-bed acute-care hospital serving a predominantly
      elderly population referred from nursing homes, as well as patients admitted from
      the community. METHODS: Interventions strategies were tested on three high-risk
      nursing stations. These included enhanced environmental sanitation; intensive
      staff retraining in Universal Precautions, body substance isolation, and proper
      use of gloves; and the use of tympanic thermometers to avoid possible rectal or
      oral VRE transmission during temperature taking. RESULTS: Nosocomial VRE
      infections were reduced by 48% 9 months after switching to tympanic thermometers;
      incidence of Clostridium difficile infections also was reduced. As a result,
      tympanic thermometers were introduced facilitywide; additional observation for 20
      months showed a risk reduction of 60% for VRE and 40% for C difficile.
      CONCLUSION: Cross-transmission of VRE and C difficile during temperature taking
      may result in bowel colonization, placing the patient at increased risk for
      infection. This risk may be reduced by the use of tympanic thermometers.

PMID- 9613695
TI  - Influenza immunization: improving compliance of healthcare workers.
AB  - OBJECTIVE: In spite of yearly recalls, influenza immunization rates of healthcare
      workers (HCWs) remained low (10%) at the University Hospitals of Geneva. This
      study was conducted to identify HCWs' reasons for rejection of immunization, to
      design specific intervention methods based on these reasons, and to evaluate the
      impact of such interventions. METHODS: Three departments with high-risk patients
      (geriatrics, obstetrics, and pediatrics) were selected as main targets.
      Questionnaires were distributed in these units. Based on HCWs' perceptions,
      different intervention methods were designed and used either in these departments
      only (educational conferences, on-site availability of a vaccination nurse) or in
      the whole institution (posters, personal letters). Immunization rates were
      collected throughout the institution. RESULTS: 797 completed questionnaires from
      1,092 HCWs (73%) were returned. Major reasons for immunization rejection were
      confidence that their bodies' self-defense mechanisms would ward off infection
      (32%), perception of low exposure risk (23%), and doubts concerning vaccine
      efficacy (19%). The use of intervention methods designed to address these factors
      increased influenza immunization rates in the three targeted departments from 13%
      (95% confidence interval [CI95], 11.4-15.6) in 1995 and 1996 to 37% (CI95, 34.5
      40.3) in the following season (P<.001). In all other departments, immunization
      rates rose from 9% (CI95, 8.5-10.3) to 23% (CI95, 21.6-24.1; P<.001). Nurses
      were, and remained, more reluctant to be immunized compared to other HCWs.
      CONCLUSIONS: Influenza immunization rates can be increased significantly by
      specific interventions based on local concerns of HCWs, among which educational
      conferences and the on-site availability of a vaccination nurse appeared
      important.

PMID- 9613696
TI  - Evidence for person-to-person transmission of Candida lusitaniae in a neonatal
      intensive-care unit.
AB  - Candida lusitaniae is an increasingly important nosocomial bloodstream pathogen.
      Epidemiological investigation and molecular typing techniques identified three
      neonates infected with identical strains of C lusitaniae that were distinguished
      readily from epidemiologically unrelated strains from other locations in the
      hospital. The results of this study provide evidence for nosocomial transmission
      of C lusitaniae in a neonatal intensive-care unit and suggest that these infants
      are at increased risk for infection with this agent.

PMID- 9613697
TI  - Pseudo-outbreak of tuberculosis in an acute-care general hospital: epidemiology
      and clinical implications.
AB  - A 10-fold increase in patients with Mycobacterium tuberculosis-positive specimens
      in one hospital laboratory prompted an investigation. Clinical and
      epidemiological data, along with M tuberculosis DNA fingerprinting results,
      indicated that laboratory contamination led to nine false-positive M tuberculosis
      cultures. Pseudo-infection should be considered in patients with unusual
      tuberculosis presentations, negative acid-fast bacilli smears, and only one
      positive culture with a low colony count.

PMID- 9613698
TI  - Report of the Council on Scientific Affairs, American Medical Association:
      immunization of healthcare workers with varicella vaccine.
AB  - OBJECTIVE: In June 1996, a resolution was introduced to the House of Delegates of
      the American Medical Association (AMA) asking the AMA to advocate that healthcare
      workers be given the informed option of receiving the varicella vaccine. The AMA
      Council on Scientific Affairs studied this issue and presented this report to the
      House of Delegates in June 1997. METHODS: Information for the report was derived
      from published literature and from personal communications with medical and
      public health experts and the vaccine manufacturer. FINDINGS: Nosocomial
      outbreaks of varicella-zoster virus (VZV) can result in serious morbidity and
      mortality. Serological testing of healthcare workers and immunization of
      nonimmune individuals is recommended by infection control and infectious disease
      experts to prevent nosocomial transmission of VZV. While current data indicate
      that the vaccine is safe and poses minimal risks to both adults and children,
      ongoing research should address various concerns about the long-term safety,
      efficacy, and epidemiological impact of more widespread use of the vaccine.
      CONCLUSION: Unless contraindicated, all susceptible healthcare workers should
      receive the varicella vaccine. Whereas individuals with a definite history of VZV
      infection can be considered immune, those with a negative or uncertain history
      should undergo serological testing and, if seronegative, should be immunized.

PMID- 9613699
TI  - Microbiological hazards related to xenotransplantation of porcine organs into
      man.
AB  - Pigs are emerging as the most likely providers of genetically engineered organs
      and cells for the purpose of clinical xenotransplantation. Introduction of
      clinical trials has been delayed primarily by uncertainties regarding the risk of
      swine pathogen transmission that could harm the recipient. The concern that
      xenotransplantation carries the potential for a new epidemic has been highlighted
      by recent experiences with both bovine spongiform encephalopathy and human
      immunodeficiency diseases. As clinical trials have been postponed and
      xenotransplantation teams are working actively to gather data for an estimation
      of the risk, this review provides the reader with a state-of-the-art estimation
      of the microbiological hazards related to xenotransplantation of porcine organs
      to man. Particular emphasis is put on viral and retroviral hazards. Both current
      diagnostic tools and those under development are described, along with breeding
      strategies to provide donor animals that would not put the recipient or the
      general population at risk.

PMID- 9613700
TI  - Nursing home infection control: a status report.
AB  - Infection control in the long-term-care facility has expanded substantially since
      "Topics in Long-Term Care" debuted in this journal in 1989. This section has been
      on hiatus, but now, after a 4-year lag, resumes its exploration of these topics.
      In the first article, endemic and epidemic infections in long-term care are
      discussed and compared to nosocomial infections in the hospital. The basic
      elements of an infection control program in this setting, as well as the recent
      advances in the field, are reviewed.

PMID- 9613701
TI  - TB transmission from medical waste.

PMID- 9613702
TI  - Trials of protecting Poland from acquiring bovine spongiform encephalopathy.
AB  - The article contains a short review on transmissible spongiform encephalopathies,
      Creutzfeld-Jakob disease (CJD) and bovine spongiform encephalopathy (BSE),
      technology of meat and bone meal production, regulations and monitoring. Poland
      has imposed a ban on the importation of live cattle, sheep, and food products of
      ruminant origin from countries where BSE has been identified. Imported meat
      should be documented with a valid certificate stating that is does not originate
      from cattle whose parents were imported from Holland, United Kingdom, Ireland and
      Switzerland. Currently no licences are being issued for importation of live
      cattle, bovine semen or bovine embryos. The Polish Ministry of Agriculture has
      appeal to born meal producers to observe the Polish Norm PN-92R-64809.

PMID- 9613703
TI  - Purification of human anti-TF (Thomsen-Friedenreich) and anti-Tn antibodies by
      affinity chromatography on glycophorin A derivatives and characterization of the
      antibodies by microtiter plate ELISA.
AB  - The TF and Tn antigens were obtained from glycophorin A (GPA) by desialylation
      under mild acidic conditions and by desialylation followed by Smith degradation,
      respectively. A method of purification of anti-TF and anti-Tn antibodies from
      human sera by affinity chromatography on the immobilized asialoGPA (TF antigen)
      and on asialo-agalactoGPA (Tn antigen), respectively, is described. Purity of the
      antibodies was demonstrated by SDS-polyacrylamide gel electrophoresis and their
      specific reactivity with TF or Tn antigens was shown using hemagglutination and
      the microtiter plate ELISA. A high unspecific binding of human immunoglobulins to
      the ELISA plates was encountered, therefore optimal conditions for the most
      specific binding of the antibodies to the target antigens were selected. Problems
      of the unspecific binding of immunoglobulins were more difficult to overcome when
      the antibodies were determined in whole sera by their binding to antigen-coated
      ELISA plates.

PMID- 9613704
TI  - Serum IgG antibodies in children and adults reacting with Helicobacter pylori
      lipopolysaccharides.
AB  - The presence of IgG antibodies reacting with Helicobacter pylori
      lipopolysaccharides (LPSs) in sera from children and adults diagnosed as H.
      pylori-infected, as well as healthy persons, was tested. There was no correlation
      between the production of antibodies reacting with H. pylori surface proteins and
      LPSs. Also no correlation between reactivity of tested sera with H. pylori
      antigens and deep rough mutant (Re types) enterobacterial LPSs was revealed. The
      prevalence of anti-LPS IgG in randomly selected children was relatively high.

PMID- 9613705
TI  - Influence of some factors on immunoassays of human myoglobin.
AB  - Six ELISA variants exploiting two monoclonal antibodies, one rabbit antibody and
      their peroxidase conjugates were applied in assays of purified human myoglobin,
      apomyoglobin and the protein in human muscle extracts. The myoglobin was
      accurately determined with monoclonal antibody no. 82 used for coating of ELISA
      plates while assays performed with monoclonal antibody no. 49 or rabbit antibody
      used for coating were weak or none. Determinations of human apomyoglobin with
      ELISA variants were somewhat more sensitive than those of myoglobin. Obtained in
      this work results were compared with those done using commercial Seratec kit for
      immunoassay of human myoglobin. Addition to the muscle extracts not only
      concentrated salts but also acetone, ethanol, sodium dodecyl sulfate or some
      other denaturing agents markedly increased assays of myoglobin by ELISA with
      monoclonal antibody no. 49 and antibody no. 82 conjugated with peroxidase.
      Removal of acetone or ammonium sulfate from extracts resulted in dramatic
      decrease of the estimated myoglobin. Filtration of the extract through Bio-Gel
      A5m column did not affect low assays of myoglobin in fractions without
      pretreatment with acetone. Myoglobin was isolated from human heart extract by
      immunoaffinity chromatography on Sepharose-antibody no. 82 column and the
      isolated protein was identified by gel electrophoresis and Western blot.

PMID- 9613706
TI  - Serum levels of tumor necrosis factor alpha and production of this cytokine by
      polymorphonuclear cells in breast cancer patients.
AB  - Unstimulated as well as zymosan and LPS-stimulated production of tumor necrosis
      factor alpha (TNF-alpha) by polymorphonuclear cells (PMNs) was investigated in
      breast cancer patients. Serum levels of TNF-alpha were also determined.
      Spontaneous TNF-alpha production was lower, comparable with that found in healthy
      persons. Zymosan and LPS-stimulated PMNs of cancer patients were found to produce
      significantly lower amounts of TNF-alpha, as compared with PMNs of healthy
      control. There was no significant differences in the serum levels of TNF-alpha
      between breast cancer patients and healthy persons. Because the peripheral blood
      cells contain more than 50% PMNs, the altered TNF-alpha production by PMNs may
      have a series of relevant implications during malignant process and seems to be
      one of the factors helpful in determining the cellular immunology potency of
      breast cancer patients.

PMID- 9613707
TI  - Lactoferrin lowers serum interleukin 6 and tumor necrosis factor alpha levels in
      mice subjected to surgery.
AB  - Mice subjected to thymectomy or splenectomy in general anesthesia release
      interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) into circulation
      reaching high concentrations after 4 h following operation. In the case of
      thymectomy IL-6 can be detected only on the day of operation and TNF-alpha
      attains a maximal value on day 3 postoperation. Splenectomy, which is a more
      extensive surgical operation, results in a higher, and more prolonged existence
      of IL-6 in circulation accompanied by higher levels of TNF-alpha. Bovine
      lactoferrin (BLF; 10 mg/mouse), given intravenously (i.v.) 24 h before
      thymectomy, reduced, on average, the level of serum IL-6 by 70% as measured 4 h
      after operation. The inhibiting effect of BLF on TNF-alpha production was smaller
      with a mean 30% reduction. The effects of BLF (i.v.) administration on the
      cytokine levels following splenectomy were less inhibitory. BLF caused an
      approximate 35% fall in IL-6 levels and even weaker effects (20% inhibition) on
      TNF-alpha release. Application of much lower (1-0.2 mg) per os doses of BLF was
      even more effective in lowering IL-6 levels after thymectomy (up to 90%) after 5
      BLF doses, and by 55% of TNF-alpha. The data suggest that lactoferrin may find
      therapeutical application for diminishing manifestations of shock caused by
      clinical insults.

PMID- 9613708
TI  - Interferon and tumor necrosis factor production during endotoxemia in sheep.
AB  - In humans endotoxemia has often been associated with the development of adult
      respiratory distress syndrome (ARDS). Sheep have an abundant population of
      pulmonary intravascular macrophages, therefore they are a popular animal model
      for ARDS. In this study we characterized the temporal sequence and duration of
      the release of two cytokines: tumor necrosis factor (TNF) and interferon (IFN)
      and evaluated the effect of lipopolysaccharide (LPS) dose. Rectal temperature and
      white blood cell (WBC) count were also measured. Twenty four adult sheep were
      given E. coli endotoxin at a dose of 0 (saline solution) 0.05, 0.1 and 1.0
      microg/kg of body weight by intravenous (i.v.) bolus. In all groups, TNF-alpha
      was produced earlier (3-4.5 h) after injection than IFN (4-5 h). No correlation
      between increased rectal temperature, the magnitude of leukopenia and time course
      of both cytokines production was observed. No straight relationship between LPS
      dose and the titer of cytokines was seen, but lower doses of LPS-induced delayed
      cytokine response in comparison to the dose 1 microg/kg of LPS. As IFN, present
      in the circulation of sheep, was mainly alpha/beta type, the role of this class
      of IFN in endotoxemia is discussed.

PMID- 9613709
TI  - Interactions of 2',2'-diflurodeoxycytidine (gemcitabine) with tumor necrosis
      factor alpha or its mutein VI in murine leukemias L1210 and P388.
AB  - The interactions of 2',2'-difluorodeoxycytidine (gemcitabine) with tumor necrosis
      factor alpha (TNF-alpha) or its mutein VI on the survival time of mice bearing
      L1210 and P388 leukemia was investigated. Four hundred eighty male CD2F1 mice
      were used in the experiments. They were given gemcitabine (20 mg/kg) on days 1,
      4, 7 and 10 after i.p. inoculation with leukemic cells (day 0). Cytokines were
      administered i.p. at a dose of 250 microg/kg as daily injections for 8 days or at
      a dose of 400 microg/kg given 2, 4, 6 and 8 days after day 0. Drugs were
      administered alone and in combination. Our study indicates that TNF-alpha and its
      mutein VI decrease the antileukemic effect of gemcitabine on murine leukemias
      L1210 and P388.

PMID- 9613710
TI  - Effect of serine proteinase inhibitors on intracellular free calcium rise in
      human polymorphonuclear leukocytes after stimulation with receptor agonists.
AB  - The respiratory burst of polymorphonuclear leukocytes depends on activation of
      many enzymes and generation of variety of second messengers. One of important
      links leading to polymorphonuclear leukocytes (PMNL) activation is a transient
      rise in intracellular free calcium concentration ([Ca2+]i). Serine proteinase
      inhibitors such as alpha-1-proteinase inhibitor (alpha1PI),
      phenylmethylsulphonylfluoride (PMSF) and soybean trypsin inhibitor (SBTI) were
      reported to inhibit human PMNL respiratory burst. In this study we tested the
      hypothesis whether these inhibitors can inhibit the rise in [Ca2+]i after
      stimulation of human PMNL with 10(-7) M n-formyl-methionyl-leucyl-phenylalanine
      (FMLP), leukotriene B4 (LTB4) or platelet activating factor (PAF). [Ca2+]i was
      measured with use of a fluorescent probe Fura-2AM under conditions of 100 nM and
      1 mM extracellular Ca2+ concentration. Preincubation of PML with 600 mg/dl of
      alpha1PI or SBTI for 30 min at 37 degrees C had no influence on Ca2+ response to
      all agonists in comparison with cells treated with the same concentration of
      human serum albumin. However, 0.5 mM PMSF enhanced 1.7-fold (p < 0.002) [Ca2+]i
      rise after challenge with FMLP while did not affect significantly Ca2+ response
      to PAF and LTB4. The stimulatory effect of PMSF after addition of FMLP was
      dependent on increased Ca2+ influx from extracellular space. Our results suggest
      that suppression of PMNL respiratory burst by serine proteinase inhibitors is not
      mediated via Ca2+ pathway and that some proteases take part in Ca2+ response to
      FMLP.

PMID- 9613711
TI  - Highlights of the Parkinson's Disease Foundation.

PMID- 9613712
TI  - Role of genetics in the cause of Parkinson's disease.

PMID- 9613713
TI  - Dietary iron, animal fats, and risk of Parkinson's disease.
AB  - BACKGROUND: Recent studies have proposed a role for diet in Parkinson's disease
      (PD). PD is characterized by a high deposition of iron and a low concentration of
      ferritin in the substantia nigra. Few data in the literature are available on the
      possible role of dietary iron in the development of PD. METHODS: In a population
      based, case-control study, we addressed the hypothesis that high dietary iron
      intake was associated with PD. We assessed dietary iron intake with a
      semiquantitative food-frequency questionnaire in 104 PD patients and 352 control
      subjects, frequency matched for age and gender. We also studied the association
      of PD and dietary iron and animal fat intake in the presence of different iron
      stores measured by transferrin saturation. RESULTS: No significant differences
      were observed between patients' and control subjects' dietary intake of iron from
      food or supplements (odds ratio [OR] for the highest quartile of intake, 0.9; 95%
      confidence interval [95% CI], 0.6, 1.3; p for trend = 0.60). Among those with low
      transferrin saturation levels (lower 50%), the odds ratio for PD associated with
      animal fat intake was ninefold higher than the risk of those with low intake (OR,
      9.0; 95% CI, 2.7-29.9). Among those with high transferrin saturation, risk of PD
      was two times higher (relative risk, 1.9; 95% CI, 0.5-7.2) for those who reported
      high intake of animal fat compared with those who reported low intake.
      CONCLUSION: Dietary iron intake after caloric adjustment was not associated with
      an increased risk of PD. However, the previously described association between
      animal fat intake and PD was modified by iron level stores as measured by
      transferrin saturation. These observations suggest that dietary fat and a
      systemic defect in iron metabolism may act synergistically in the process of
      lipid peroxidation in PD.

PMID- 9613714
TI  - Programmed cell death and Parkinson's disease.

PMID- 9613715
TI  - Oxidative mechanisms in nigral cell death in Parkinson's disease.
AB  - Oxidative stress may contribute to nigral cell death in Parkinson's disease based
      on postmortem investigations showing increased iron levels, decreased levels of
      reduced glutathione (GSH), and impaired mitochondrial function. This leads to
      oxidative damage because lipid peroxidation is increased in substantia nigra and
      there is a widespread increase in protein and DNA oxidation in the brain in
      Parkinson's disease. Nitric oxide (NO) may be one of the free radical species
      involved in nigral degeneration. NO is involved in the production of hydroxyl
      radicals resulting from MPP+-induced dopamine efflux in striatum. Mice treated
      with the neuronal nitric oxide synthase (NOS) inhibitor 7-nitroindazole show
      reduced toxicity to MPTP and knock-out mice lacking neuronal NOS show decreased
      MPTP susceptibility. In primates, 7-nitroindazole inhibits MPTP toxicity but this
      remains controversial because no protection is afforded by the nonspecific NOS
      inhibitor, L-NAME. Indeed, in Parkinson's disease itself, there is little
      evidence for nitric oxide's involvement in nigral pathology. A susceptibility
      factor for the development of Parkinson's disease may involve isoforms of
      cytochrome P450, some of which are found in the brain. CYP2EI, which is
      associated with free radical production and the formation of endogenous toxins,
      is selectively localized in nigral dopamine-containing cells. CYP2E1 metabolizes
      n-hexane leading to the formation of its neurotoxic metabolite 2,5-hexanedione
      which may explain cases of solvent-induced parkinsonism. Oxidative processes
      clearly contribute to the pathology of Parkinson's disease but are probably
      secondary to some other primary unidentified cause, presumably genetic or
      environmental. Nevertheless, their involvement may allow therapeutic intervention
      in the cascade of events associated with the progression of Parkinson's disease.

PMID- 9613716
TI  - Mechanisms of MPTP toxicity.
AB  - 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces an experimental
      model of Parkinson's disease (PD). It replicates most of the clinical features of
      PD as well as the main biochemical and pathologic hallmarks of the disease.
      Although the MPTP model departs from PD in several aspects, it is thought that
      important insights into the neurodegenerative process of PD may be obtained by
      elucidating the molecular mechanism of MPTP. In this article, we summarize the
      different steps of the complex metabolic pathway of MPTP and show how they may be
      implicated in predisposing individuals to PD. We also outline findings pertinent
      to the mode of action of MPTP including overproduction of free radicals,
      implication of nitric oxide, nitration of tyrosine, impairment of mitochondrial
      respiration, and occurrence of apoptosis. All of these factors may participate in
      the cascade of deleterious events that ultimately lead to the death of
      dopaminergic neurons after MPTP administration. Because of the similarity between
      PD and the MPTP model, we are speculating that a similar scenario may underlie
      the neurodegenerative process in PD.

PMID- 9613717
TI  - Iron metabolism and Parkinson's disease.
AB  - There are at least three major reasons for thinking that iron participates in the
      mechanism of nerve cell death in Parkinson's disease (PD): (1) Iron catalyzes the
      formation of highly toxic hydroxyl radicals through the Fenton reaction. (2)
      Evidence suggests that oxidative stress participates in the mechanism of nerve
      cell death in PD. (3) Increased iron concentrations have been observed in the
      substantia nigra of patients with PD. In this review, we report data suggesting
      that the vulnerable neurons in PD are particularly sensitive to oxidative stress
      that may be induced by iron and then discuss the mechanisms by which iron levels
      may be increased in dopaminergic neurons in PD.

PMID- 9613718
TI  - Where do we stand on neuroprotection? Where do we go from here?
AB  - Neuroprotective therapies are interventions that produce enduring benefits by
      favorably influencing underlying etiology or pathogenesis of neurodegenerative
      disorders. Neuroprotection remains an unachieved goal of experimental
      therapeutics. A variety of pathogenetic mechanisms and propagating factors have
      been implicated in the emergence and progression of Parkinson's disease (PD).
      Antioxidative strategies have been the focus of neuroprotective trials for PD,
      but interpretation of the outcomes has been controversial. Traditional end points
      that respond to enhanced dopaminergic activity may not be suitable for
      distinguishing symptomatic from neuroprotective effects. Inferences supporting
      neuroprotective effects in clinical trials would be strengthened by attention to
      unmet therapeutic needs or relevant clinical end points that are not currently
      amenable to dopaminergic treatments. Progressive postural instability and
      intellectual impairment (dementia) represent two major unmet therapeutic needs in
      PD that are worthy outcomes in therapeutic trials. Imaging tools such as [18F]
      dopa PET and [123I] B-CIT SPECT may provide valid and reliable biologic markers
      of nigrostriatal degeneration. Controlled clinical trials focused on unmet
      therapeutic needs, and involving valid biologic markers is expected to play a
      central role in development of neuroprotective therapy for PD.

PMID- 9613719
TI  - A preclinical development strategy designed to optimize the use of glial cell
      line-derived neurotrophic factor in the treatment of Parkinson's disease.
AB  - GDNF is a pleitropic neurotrophic factor which stimulates the dopaminergic
      phenotype in vitro and in vivo by way of activation of the GDNF/RET receptor
      complex. The pharmacologic profile of GDNF in two well-characterized animal
      models of Parkinson's disease suggests that the molecule may be useful in the
      treatment of neurodegenerative diseases involving dopaminergic dysfunction such
      as Parkinson's disease. This review summarizes the preclinical development path
      which was taken to develop GDNF as a novel therapeutic approach to treat
      Parkinson's disease based on GDNF's ability to regenerate dopamine neurons,
      including a description of the pharmacologic/biologic activities of GDNF. The
      overall aim will be to discuss these issues in the context of their potential
      therapeutic usefulness of GDNF to treat Parkinson's disease.

PMID- 9613720
TI  - Current status of selegiline as a neuroprotective agent in Parkinson's disease.

PMID- 9613721
TI  - Potential of gene therapy for Parkinson's disease: neurobiologic issues and new
      developments in gene transfer methodologies.
AB  - Gene transfer techniques have been explored as therapeutic modalities and
      neurobiologic tools to understand the role of various genes in animal models of
      Parkinson's disease. The gene for tyrosine hydroxylase, the rate-limiting step of
      dopamine synthesis, has been transferred into animal models by viral vectors or
      by implantable cells that have been modified by retrovirus vectors. The role of
      additional genes such as GTP cyclohydrolase 1 and aromatic L-amino acid
      decarboxylase in optimal delivery of dopamine in animal models is reviewed. Gene
      therapy also allows goals beyond replacement of dopamine. Neurotrophic factors
      such as brain-derived neurotrophic factor and glial cell line-derived
      neurotrophic factor can be introduced to promote sprouting of neurites and
      protect the dopaminergic neurons from degeneration. Genes involved in apoptosis,
      free radical scavenger pathway, or other cell death mechanism could also be used
      to prevent the degeneration of the neurons. Current technology of gene therapy is
      limited in its long-term expression and ability to regulate the gene expression.
      However, recent developments provide better understanding of these limitations
      and suggest potential solutions to these technical hurdles.

PMID- 9613722
TI  - Pallidotomy and deep brain stimulation of the pallidum and subthalamic nucleus in
      advanced Parkinson's disease.
AB  - There has been a resurgence in the use of neurosurgical procedures for the
      treatment of Parkinson's disease (PD). Pallidotomy has become a widely performed
      procedure on the basis of reports which describe marked reduction of levodopa
      induced dyskinesias and variable improvement in parkinsonism. Preliminary reports
      of the effects of globus pallidus internus (GPi) and subthalamic nucleus (STN)
      deep brain stimulation (DBS) have also been promising. At 6-month follow up, a
      cohort of our first 40 patients undergoing pallidotomy demonstrated the following
      mean improvements when examined after drug withdrawal (off) and under optimal
      medication (on): total motor off scores-31%; total off activities of daily living
      scores-30%; and total on dyskinesias-63% (contralateral and ipsilateral
      dyskinesias improved 82% and 50%, respectively). Although improvements in
      contralateral dyskinesias and total off parkinsonism were sustained at 2-year
      follow up (N = 11), benefit for ipsilateral dyskinesias was lost after 1-year
      follow up (N = 24). and postural stability and gait improvements lasted only 3-6
      months. On-period, levodopa-resistant symptoms did not benefit from pallidotomy.
      Mean improvements in 8 patients undergoing GPi DBS (4 unilateral and 4 bilateral)
      at 3 months were as follows: total motor off scores-27%; total off activities of
      daily living scores-26%; and total on dyskinesias-60%. At most recent follow up,
      6 patients with STN DBS (5 bilateral and 1 unilateral) showed the following mean
      improvements: total motor off scores-41%; total motor on scores-27%; total off
      activities of daily living scores-40%; and total on dyskinesias 41%. Pallidotomy
      reduces dyskinesias and off disability. GPi DBS may have effects similar to
      pallidotomy, but might be safer when bilateral procedures are required. Bilateral
      STN DBS may improve off parkinsonism more than other procedures and might also
      improve on-period motor function. A randomized trial will be required to
      determine which procedure is most effective for patients with different clinical
      features.

PMID- 9613723
TI  - Update on fetal transplantation: the Swedish experience.
AB  - We implanted human embryonic mesencephalic tissue into the striatum of 13
      patients with idiopathic Parkinson's disease (PD) and three patients with MPTP
      induced parkinsonism. Based on our findings so far, as well as data from other
      groups, the following conclusions can be drawn: First, grafted dopamine (DA)
      neurons can survive in the human parkinsonian brain and reinnervate part of the
      host striatum. Second, long-term graft survival, at least up to 6 years after
      transplantation, is possible in PD despite a progressive degeneration of the
      patient's own DA neurons. Third, a majority of patients with surviving grafts
      show long-term improvement of therapeutic value but the symptomatic relief is, in
      most cases, incomplete. Presently, the most important research strategy to
      improve the functional recovery after transplantation is to increase the survival
      of grafted DA neurons and the density and extent of the dopaminergic
      reinnervation in the striatum.

PMID- 9613724
TI  - Neuropathology of fetal nigral grafts in patients with Parkinson's disease.

PMID- 9613725
TI  - Clozapine use in Parkinson's disease: a retrospective analysis of a large
      multicentered clinical experience.
AB  - We conducted a multicentered, retrospective review of clozapine's (CZP) effects
      on a range of psychiatric, sleep, cognitive, motor, and sensory disorders in
      Parkinson's disease (PD). Therapeutic outcomes and adverse events were compared
      with varying prescribing practices at participating sites. The medical records of
      172 consecutive PD patients treated with CZP at four movement disorder clinics
      were reviewed. Low-dose CZP improved psychiatric symptoms of psychosis, anxiety,
      depression, hypersexuality, sleep disturbance, and akathisia. Tremor,
      torticollis, limb dystonia, and pain showed modest rates of improvement. Twenty
      three percent of patients withdrew as a result of adverse events or treatment
      failure. Inpatient CZP initiation did not improve therapeutic efficacy, or reduce
      adverse events or the withdrawal rate. Low-dose CZP in the outpatient setting is
      generally an effective and well-tolerated treatment for many of the psychiatric,
      sleep, motor, and sensory disturbances common to late-stage PD.

PMID- 9613727
TI  - Clinical assessment of olfactory dysfunction in Parkinson's disease.
AB  - We used two simple tasks to test the capacities of patients with Parkinson's
      disease to discriminate and identify olfactory stimuli. The patients presented
      defective odor identification abilities whereas their capacity to discriminate
      between odors was apparently unaffected. This raises a question about the nature
      of olfactory dysfunction in Parkinson's disease. Further clinical data is
      required for analysis of this dysfunction. We therefore propose simple and rapid
      tests appropriate for clinical use with Parkinson's disease patients.

PMID- 9613726
TI  - Fetal nigral grafts survive and mediate clinical benefit in a patient with
      Parkinson's disease.
AB  - We have previously demonstrated that fetal nigral grafts can survive, reinnervate
      the striatum, and mediate clinically relevant recovery in a patient with
      Parkinson's disease (PD). Most previous autopsy cases have failed to identify
      meaningful numbers of viable grafted cells suggesting that differences in
      critical transplant variables determine graft viability. The present study
      evaluated the structural and functional correlates of fetal nigral
      transplantation in a second PD patient who received fetal nigral grafts according
      to our previously published transplant protocol. A 61-year-old woman with severe
      PD received bilateral fetal nigral grafts to the postcommissural putamen from
      seven donor fetuses (four right side and three left side) aged 6.5-9 weeks
      postconception. This patient died 19 months after surgery from a cause unrelated
      to the transplant surgery. Her postoperative clinical course was characterized by
      improved motor and activities of daily living scores during "off time," reduced
      "off time," and increased "on" time without dyskinesia. Positron emission
      tomography (PET) scans revealed a bilateral and progressive increase in
      fluorodopa (FD) uptake within the grafted putamen. Postmortem examination of the
      right hemisphere revealed large oval-shaped grafts containing more than 138,000
      tyrosine-hydroxylase-immunoreactive (TH-ir) neurons. Grafted cells formed a
      seamless border with the host and provided dense TH-ir innervation to 78% of the
      host postcommissural putamen. Graft-mediated sprouting of host fibers was not
      observed. These data provide essential confirmation that, under appropriate
      transplant conditions, grafted nigral neurons can survive, reinnervate the host
      striatum, and provide clinical benefit to PD patients. These findings also
      support the concept that improved motor function and striatal FD uptake on PET
      after nigral grafting in PD are the result of the viability of grafted neurons
      and graft-derived reinnervation of the host striatum.

PMID- 9613728
TI  - Prevalence of Parkinson's disease in Northwestern Italy: comparison of tracer
      methodology and clinical ascertainment of cases.
AB  - The prevalence of idiopathic Parkinson's disease (PD) in an area of Northwestern
      Italy (Socio-Sanitary District of Cossato, 61,830 inhabitants) was analyzed and
      the reliability of "drug tracer methodology" evaluated. The patients were
      identified by both conventional epidemiological methodology (general
      practitioners, consultant neurologist, computerized archives) and drug tracer
      methodology (registered levodopa prescriptions). The diagnosis of PD was
      clinically verified by examining all patients. Of 146 patients examined, 104 were
      affected by PD; the remaining by other types of parkinsonism. The crude point
      prevalence rate (October 20, 1991) was 168 per 100,000 population (95% confidence
      interval [95% CI] 138-204), with a progressive increase up to the 80-89 age
      group. Using "tracer" methodology, the estimated crude point prevalence rate was
      196 (95% CI 163-235), with an overestimation of the prevalence in older patients
      and women and an underestimation in younger and less seriously affected cases.
      The uneven distribution of PD in Italy appears to be the result of, at least in
      part, methodological factors. "Tracer" methodology may cause biases in the
      evaluation of the epidemiological characteristics of PD, especially if the
      clinical diagnosis of cases identified by this method is not carefully verified.
      Nevertheless, it appears useful as an additional source of cases for descriptive
      surveys.

PMID- 9613729
TI  - The health burdens of Parkinson's disease.
AB  - Parkinson's disease (PD) is likely to have a substantial impact on an
      individual's health-related quality of life (HRQL), health-related resource use,
      and productivity. Data about the health burdens of PD by disease stage are
      fundamental to understanding the effectiveness of care, both from a clinical and
      a fiscal point of view. This study's goal was to describe the associations of
      patient-reported HRQL and economic characteristics with PD stage. We hypothesized
      that later stages of PD would be associated with poorer HRQL, greater health
      related resource use, and lower work productivity than early stages of PD. We
      used a cross-sectional analysis to study 193 PD patients attending two hospital
      based neurology clinics. Self-administered questionnaires and in-person
      interviews measured clinical features, functional status, general health
      perceptions, well-being, overall HRQL, work productivity, and health-related
      resource use. Consistent, strong associations were found between stage and
      functional status, general health perceptions, well-being, and overall HRQL even
      after controlling for age, gender, and comorbid conditions. Most resource use and
      work productivity measures were also associated with disease stage. However,
      physician services use was not. This study confirms that the burdens of illness
      are progressively higher for PD patients with early, moderate, and advanced
      illness. The results suggest that such important facets of the health burden as
      HRQL and health-related resource use may be seriously misjudged if not carefully
      measured but inferred from clinical observations alone.

PMID- 9613730
TI  - A trial of dextromethorphan in parkinsonian patients with motor response
      complications.
AB  - The effects of the NMDA antagonist dextromethorphan (DM) on levodopa-associated
      dyskinesias and motor fluctuations were studied in patients with advanced
      Parkinson's disease. During initial open-label dose escalation, 6 of 18 patients
      reported a beneficial effect at their individually determined optimal DM dose
      (range, 60-120 mg/day). The 12 remaining patients either experienced reversible
      side effects, particularly mild drowsiness, or decreased levodopa efficacy, and
      were therefore excluded from the study. The six responders entered the double
      blind, placebo-controlled, crossover study with two 2-week arms separated by 1
      week wash-out. On the last day of each arm, motor ratings were performed every 20
      minutes for 8 consecutive hours. In addition, motor complications and Activities
      of Daily Living (ADL) were assessed using the Unified Parkinson's Disease Rating
      Scale (UPDRS) and patient diaries. With DM, dyskinesias improved by 25% according
      to physician's ratings and by 40% according to UPDRS interviews, without
      compromising the anti-Parkinson effect of levodopa. Motor fluctuations and ADL
      scores also improved significantly. Although the narrow therapeutic index of DM
      limits its clinical usefulness, these findings support the view that drugs acting
      to inhibit glutamatergic transmission at the NMDA receptor can ameliorate
      levodopa-associated motor complications.

PMID- 9613731
TI  - Clinical impairment of sequential finger movements in Parkinson's disease.
AB  - A retrospective analysis was performed on the records of 33 off-therapy
      parkinsonian patients. We analyzed the clinical score of three sequential upper
      limb movements: finger tapping, hand opening and closing, and forearm pronation
      and supination. The records showed that nearly all patients had difficulty in
      performing all three motor tasks, but movement scores showed that they found the
      sequential finger-tapping task significantly more difficult than the other two
      tasks. We suggest that parkinsonian patients find individual finger movements
      more difficult to execute than gross hand movements because--owing to their
      abnormal basal ganglia output--they lack the finer cortical control and greater
      facilitation that the finger task demands.

PMID- 9613732
TI  - Hypometria in Parkinson's disease: automatic versus controlled processing.
AB  - OBJECTIVES: The aim was to investigate whether patients with Parkinson's disease
      (PD) make movements that are of smaller amplitude when required to attend to a
      secondary task at the same time as performing a motor task. METHODS: Thirteen
      patients with idiopathic Parkinson's disease (mean age, 67.1 yrs) and 14 healthy
      control subjects (mean age, 66.2 yrs) were tested. The motor task was repeated
      opposition of the thumb and forefinger and the secondary task was a lexical
      decision task. RESULTS: The PD patients made hypometric movements, and the
      amplitude was further decreased when they performed the secondary task at the
      same time. There was no significant change for the control subjects. CONCLUSION:
      The unpaced motor task was less automatic for the PD patients than for the
      control subjects, and hence more subject to interference from a secondary task.
      We relate this to the underactivation of the supplementary motor cortex (SMA).

PMID- 9613733
TI  - Gait variability and basal ganglia disorders: stride-to-stride variations of gait
      cycle timing in Parkinson's disease and Huntington's disease.
AB  - The basal ganglia are thought to play an important role in regulating motor
      programs involved in gait and in the fluidity and sequencing of movement. We
      postulated that the ability to maintain a steady gait, with low stride-to-stride
      variability of gait cycle timing and its subphases, would be diminished with both
      Parkinson's disease (PD) and Huntington's disease (HD). To test this hypothesis,
      we obtained quantitative measures of stride-to-stride variability of gait cycle
      timing in subjects with PD (n = 15), HD (n = 20), and disease-free controls (n =
      16). All measures of gait variability were significantly increased in PD and HD.
      In subjects with PD and HD, gait variability measures were two and three times
      that observed in control subjects, respectively. The degree of gait variability
      correlated with disease severity. In contrast, gait speed was significantly lower
      in PD, but not in HD, and average gait cycle duration and the time spent in many
      subphases of the gait cycle were similar in control subjects, HD subjects, and PD
      subjects. These findings are consistent with a differential control of gait
      variability, speed, and average gait cycle timing that may have implications for
      understanding the role of the basal ganglia in locomotor control and for
      quantitatively assessing gait in clinical settings.

PMID- 9613734
TI  - 123I-beta-CIT and 123I-IBZM-SPECT scanning in levodopa-naive Parkinson's disease.
AB  - Striatal dopamine transporter function and dopamine D2 receptor status were
      evaluated in 15 patients with early untreated Parkinson's disease using single
      photon emission tomography (SPECT) with 123I-Iodo-2beta-carboxymethoxy-3beta-(4
      idiophenyl)tropane (beta-CIT) and 123I-Iodobenzamide (IBZM) as pre- and
      postsynaptic ligands. Symptoms were unilateral in five patients and bilateral but
      asymmetric in 10 patients. Patients with bilateral symptoms had significantly
      lower 18-hour striatal/cerebellar beta-CIT binding ratios (3.59 +/- 0.79) than
      hemiparkinsonian patients (5.76 +/- 1.48, p < 0.05) reflecting more advanced
      disease in this subgroup. Patients with bilateral parkinsonism were also found to
      have a significant side-to-side difference in striatal beta-CIT binding with more
      marked reduction contralateral to the presenting limb (18-hour
      striatal/cerebellar ratio: 4.13 +/- 0.78 [ipsilateral] versus 3.59 +/- 0.79
      [contralateral], p < 0.05). Dopamine D2 receptor binding as measured by IBZM was
      significantly elevated contralateral to the affected side in hemiparkinsonian
      patients (striatal/cerebellar ratio: 2.42 +/- 0.90 [contralateral] versus 2.19 +/
      0.80 [ipsilateral], p < 0.05). This asymmetric upregulation was absent in the
      patients with bilateral parkinsonism (striatal/cerebellar ratio: 1.85 +/- 0.43
      [contralateral to more severely affected side] versus 1.83 +/- 0.34
      [ipsilateral], p > 0.05). Our data suggest that postsynaptic dopamine receptor
      upregulation contralateral to the presenting side occurs in untreated unilateral
      PD and disappears in untreated bilateral (asymmetric) PD despite a greater loss
      of dopamine transporter function. Combined beta-CIT and IBZM SPECT studies may be
      helpful to monitor the progression of nigrostriatal dysfunction in early PD.

PMID- 9613735
TI  - Do visual-evoked potentials and spatiotemporal contrast sensitivity help to
      distinguish idiopathic Parkinson's disease and multiple system atrophy?
AB  - A large number of patients with Parkinson's disease were reported to have
      abnormal visual-evoked potentials (VEPs) and spatiotemporal contrast sensitivity
      (STCS) suggesting dopaminergic deficiency in the visual pathway, probably the
      retina. Until now, VEPs and STCS have not been studied in multiple system atrophy
      (MSA). We investigated 12 patients with idiopathic Parkinson's disease (IPD) and
      12 patients with MSA. The age medians were 64.5 years for IPD and 63.5 years for
      MSA. None of the patients showed any ocular disease that could interfere with the
      results. Checkboard VEPs and STCS measurements to horizontal sinusoidal gratings
      were evaluated. Statistical analysis was performed, including Student's t test
      and two- or three-way analysis of variance. A significant interocular difference
      in spatial contrast sensitivity was observed in IPD, which was not present in
      MSA. VEPs were not delayed in MSA, whereas latency of the major component and the
      second negative deflection were increased in IPD. VEPs and STCS measurements
      might provide useful help for distinguishing IPD from MSA.

PMID- 9613736
TI  - Cinnarizine-induced parkinsonism: ten years later.
AB  - A retrospective study was carried out to investigate the evolution of patients
      diagnosed with cinnarizine-induced parkinsonism (CIP) over the past 15 years. A
      total of 74 cases of CIP were found among 172 patients with drug-induced
      parkinsonism (DIP). Both CIP and other DIP were significantly more frequent in
      women. No clinical differences between CIP and other DIP were found. Most of the
      patients (66 of 74) completely recovered after cinnarizine withdrawal in 1-16
      months. Eleven patients later developed Parkinson's disease; four of them had
      previously recovered. Five patients had tardive dyskinesia. CIP accounts for a
      high proportion of DIP referred to neurologists in populations in which
      cinnarizine is widely prescribed. The symptoms typically resolve after drug
      withdrawal, although complete recovery may take more than 1 year.

PMID- 9613737
TI  - Tremor in ostensibly normal elderly people.
AB  - Tremor in ostensibly normal people, aged 70-91, was assessed clinically and
      electrophysiologically with the goal of estimating the prevalence of abnormal
      tremor. Fifty men and 50 women, mean age 76.0 +/- 4.7 yrs, were recruited through
      advertisements for healthy volunteers (n = 50 "biased" control subjects) and from
      the spouses of patients referred to us for dementia or Parkinson's disease (n =
      50 "unbiased" control subjects). All participants were interviewed and examined
      by the author. Tremor was assessed quantitatively with rating scales, triaxial
      accelerometry, electromyography, a digitizing tablet, and spectral analysis.
      Twenty-three people (23%) were judged clinically to have mildly abnormal tremor
      resembling mild essential tremor. Twelve people with abnormal tremor belonged to
      the biased group and 11 were in the unbiased group. The clinical diagnosis of
      abnormal hand tremor correlated well with the presence of motor unit entrainment
      in the forearm EMG and with writing or drawing tremor that was measurable with a
      digitizing tablet. Only 10 of 23 people with abnormal tremor were aware of their
      tremor, and none had been diagnosed previously by a physician. Nine of 77 people
      (11.7%) with normal tremor had a parent or sibling with possible essential
      tremor, and five of the 23 people (21.7%) with abnormal tremor had this family
      history. Mild undiagnosed tremor, resembling essential tremor, is common in this
      age group.

PMID- 9613738
TI  - Double-blind controlled trial of gabapentin in essential tremor.
AB  - Gabapentin has been reported to be effective for essential tremor (ET) based on
      open-label trials. We studied gabapentin (1800 mg/day) and placebo in a double
      blind crossover design in 20 ET patients. Eighteen patients completed the study
      and two patients dropped out as a result of adverse effects which resolved when
      the medication was discontinued. Tremor was assessed at baseline and after 2
      weeks of gabapentin and placebo treatment. One patient was mildly improved and
      another was moderately improved with placebo. Similarly, one patient reported
      mild improvement and another patient had marked improvement with gabapentin. All
      the remaining patients either reported no change or were worse with both
      treatment arms. There was no significant difference for total tremor score, hand
      tremor score, handwriting scores, or pouring scores. Sickness Impact Profile
      scores were no different between placebo and gabapentin. Our results suggest that
      as an adjuvant therapy in ET, gabapentin has limited benefit.

PMID- 9613739
TI  - Limb-kinetic apraxia.
AB  - Five cases of limb-kinetic apraxia following primary degenerative cerebral
      pathology are reported. Apraxia appeared as the main symptom and was not
      concomitant to aphasia or to widespread cognitive impairments. Apraxia was not a
      consequence of elementary motor or sensory deficits, lack of coordination, or the
      result of the presence of rigid-akinetic symptoms. The apraxia was usually
      unilateral, being present in both routine activities and testing sessions and
      consisting of the coarse, unilateral, awkward execution of correctly planned
      movements. Conceptual knowledge of the movements and their ideational plan was
      spared. The characteristics of apraxia fit the definition of limb-kinetic apraxia
      originally proposed by Liepmann. The pertinent literature is reviewed.

PMID- 9613740
TI  - Hyperkinetic movement disorders misdiagnosed as tics in Gilles de la Tourette
      syndrome.
AB  - OBJECTIVE: To describe the gamut of movements misdiagnosed as tic exacerbations
      in Gilles de la Tourette syndrome (GTS) in a referral tertiary-care center.
      BACKGROUND: Movements seen in GTS can be classified as: (a) tics; (b) movements
      related to conditions associated with GTS, specifically obsessive-compulsive
      disorder (OCD), attention deficit hyperactivity disorder (ADHD), and antisocial
      behaviors; and (c) movements secondary to treatment. METHODS: We reviewed a
      videotape database and patient records from a tertiary treatment center for GTS
      and collected GTS cases referred for disease exacerbation who had both tics and
      non-tic movements thought by the referring physician, the patient, and the family
      to be an exacerbation of tics. RESULTS: Of 373 GTS cases, 12 had movement
      disorders secondary to treatment, and six had non-tic movements related to
      conditions commonly associated with GTS. In the former group, there were 7
      patients with acute akathisia, 3 with acute dystonia, 1 with tardive chorea, 1
      with withdrawal emergent chorea, and 5 with tardive dystonia. Six had movement
      disorders related to non-tic conditions commonly associated with GTS: four
      patients had movements associated with OCD, one with ADHD and antisocial
      behavior, respectively. CONCLUSION: There is a broad spectrum of movements in GTS
      that are not tics but can be misdiagnosed as tics. Clinical awareness of these
      movements is paramount to proper diagnosis and pharmacologic intervention.

PMID- 9613741
TI  - Comparison of acute- and delayed-onset posttraumatic cervical dystonia.
AB  - Head, neck, or shoulder trauma is an occasional antecedent event before the
      appearance of cervical dystonia. A clinically distinctive syndrome of acute-onset
      posttraumatic cervical dystonia characterized by markedly restricted range of
      neck motion, absence of phasic involuntary movements, and poor response to
      treatment has previously been described. Patients with cervical dystonia
      attending a movement disorder clinic were reviewed for history of trauma before
      onset of symptoms. Patients with symptom onset within 4 weeks of trauma were
      compared with patients who developed symptoms between 3 months and 1 year after
      trauma. Acute-onset cervical dystonia was characterized by markedly reduced
      cervical mobility; prominent shoulder elevation with trapezius hypertrophy in
      most patients, absence of involuntary movements, sensory tricks, or activation
      maneuvers; and poor response to botulinum toxin injection. By contrast, delayed
      onset cervical dystonia was clinically indistinguishable from nontraumatic
      idiopathic cervical dystonia. Acute-onset posttraumatic cervical dystonia is
      similar to limb dystonia after peripheral trauma and may represent a form of
      nondystonic muscle spasm similar to torticollis associated with musculoskeletal
      injuries of the cervical spine and craniocervical junction.

PMID- 9613742
TI  - Clinical comparison of tardive and idiopathic cervical dystonia.
AB  - It has been suggested that tardive cervical dystonia may be clinically
      indistinguishable from the idiopathic form and that the diagnosis rests solely on
      documenting an exposure to dopamine antagonist medications. To investigate this,
      we performed a retrospective evaluation of patient records on 102 patients with
      idiopathic and 20 patients with tardive cervical dystonia seen in our Movement
      Disorder Clinic over the past 8 years. Several clinical and demographic variables
      were compared and a number of differences were observed. The presence of
      extracervical involvement, retrocollis, and spasmodic head movements were
      individually found to be predictive of tardive cervical dystonia. Torticollis,
      laterocollis, and trick maneuvers were predictive of idiopathic cervical
      dystonia. Head tremor (42.2%) and family history of dystonia (9.8%) were present
      only in the idiopathic group. Cervical muscle hypertrophy was significantly more
      common in the idiopathic group (100% versus 75%). No difference was found between
      the two groups in their response to treatment with botulinum toxin A. These
      results indicate that clinical differences between idiopathic and tardive
      cervical dystonia exist. These differences may help to distinguish them in the
      clinical setting, improve diagnostic accuracy, and support the existence of a
      causal relationship between exposure to dopamine antagonist medications and
      chronic dystonia.

PMID- 9613743
TI  - The effect of changes in head posture on the patterns of muscle activity in
      cervical dystonia (CD).
AB  - Twelve patients with cervical dystonia (CD) and predominant rotation were studied
      to determine the effects of changes in head posture on the specific patterns of
      cervical muscle activity. Turns analysis was used to quantify muscle activity
      underlying head rotation, recorded simultaneously from the agonist and antagonist
      muscle pairs bilaterally (sternocleidomastoid [SCM] and splenius [SPL]). Muscle
      activity was compared between the uncompensated dystonic posture and during the
      maintenance of midposition. In addition, patients were separated into two groups
      (geste = 6; no geste = 6) based on whether they had a clinically efficacious
      geste to determine the effect of geste on patterns of cervical muscle activity.
      Muscle activity was measured during the maintenance of midposition with and
      without a clinical or simulated geste. Differences in muscle activity between the
      groups and postures were compared using repeated measure analysis of variance
      (ANOVA) analyses. The four muscles tested showed a significant difference in
      muscle activity in the uncompensated dystonic posture as a result of the
      increased activity in the agonist muscle pair (SCM and SPL responsible for the
      dystonic posture) (EMG amplitude: F[1,11] = 18.81, p = 0.0012; EMG frequency:
      F[1,11] = 32.07, p = 0.0001). Maintaining the head in the midposition was
      associated with a significant reduction in muscle activity compared with the
      uncompensated dystonic posture (EMG amplitude: F[1,9] = 6.36, p < 0.033; EMG
      frequency: F[1,9] = 10.96, p < 0.0091). This reduction in midposition muscle
      activity was significantly greater in the agonist muscle pair (EMG amplitude:
      F[1,10] = 19.70, p = 0.0013; EMG frequency: F[1,10] = 44.67, p < 0.0001). In the
      patients with clinically effective geste, there was no additional reduction in
      muscle activity observed in the midposition when they performed their geste (EMG
      amplitude: F[1,9] = 4.63, p = 0.060; EMG frequency: F[1,9] = 1.22, p = 0.298).
      These findings suggest that CD with rotation is characterized by predominantly
      increased agonist muscle activation. Patients with CD retain the ability to
      modulate this involuntary agonist muscle activity to maintain the head in the
      midposition. The maintenance of the midposition does not seem to be facilitated
      by geste.

PMID- 9613744
TI  - Cerebral and cerebellar activation in correlation to the action-induced dystonia
      in writer's cramp.
AB  - The pattern of brain perfusion of four patients with writer's cramp and four
      control subjects were examined using positron emission tomography scans after
      [(15)O] butanol injections. Each subject was scanned 12 times to cover three
      repetitions of four different motor tasks with the right hand. Drawing of
      horizontal lines and variable durations of the writing of a prelearned text were
      performed in a pseudorandom order, the latter task commencing either
      simultaneously with or 30 sec or 120 sec before the tracer injection. The
      perceived difficulty and signs of dystonia progressed in correlation to the
      duration of writing. Statistical parametric maps were calculated to test
      hypotheses of regional specific effects dependent on the performed motor tasks.
      The patients with writer's cramp had progressively increased activity in the left
      primary sensorimotor and premotor cortices, the left thalamus, and the cerebellum
      with a right-side predominance in correlation to the duration of writing. The
      regions with activity increases thus corresponded to a cerebrocerebellar motor
      circuit. The duration of writing correlated to a progressive reduction of
      activity in the patients' left supramarginal and angular gyri (Brodmann areas 40
      and 39) and an inferior part of the left temporal lobe (area 20). The control
      subjects had neither a significant increase or decrease of activity in
      correlation to the duration of writing. Group-specific differences were confirmed
      statistically in split-plot interaction analyses.

PMID- 9613745
TI  - Quantitative EEG analysis of depth electrode recordings from several brain
      regions of mutant hamsters with paroxysmal dystonia discloses frequency changes
      in the basal ganglia.
AB  - Computerized EEG spectral analyses of depth electrode recordings from striatum
      (caudate/putamen; CPu), globus pallidus (GP), and parietal cortex (pCtx) were
      performed before and after dystonic attacks in freely moving mutant dt(sz)
      hamsters with paroxysmal dystonia. In these hamsters, sustained attacks of
      abnormal movements and postures can be reproducibly induced by stress, such as
      placing the animals in a new environment. Data recorded from mutant hamsters were
      compared with recordings from age-matched nondystonic control hamsters. The
      predominant EEG changes in CPu and GP of dystonic hamsters were significant
      decreases in the high-frequency beta2 range and there was a tendency to increase
      in delta and theta activities. These changes were seen both before and after
      onset of dystonic attacks, indicating a permanent disturbance of neural
      activities in the basal ganglia of dystonic animals. No such changes were seen in
      the pCtx. Furthermore, no epileptic or epileptiform activity was seen in any of
      the recordings, substantiating a previous notion from cortical and hippocampal
      recordings that paroxysmal dystonia in these mutant hamsters has no epileptogenic
      basis. The present finding of abnormal synchronization of neural activity in the
      CPu and GP of dystonic hamsters adds to the belief that the striatopallidal
      thalamocortical circuit is the most likely site in which to search for the
      unknown defect in primary (idiopathic) dystonia. As suggested by this study,
      quantitative EEG analysis can increase the likelihood of detecting subtle EEG
      abnormalities in different types of idiopathic dystonia and thereby improves our
      understanding of the pathogenetic mechanisms of this movement disorder.

PMID- 9613746
TI  - Monoaminergic effects of high-dose corticotropin in corticotropin-responsive
      pediatric opsoclonus-myoclonus.
AB  - Children with the opsoclonus-myoclonus syndrome (OMS) usually respond to
      corticotropin (adrenocorticotrophic hormone, ACTH) treatment but the mechanism of
      benefit is unknown. We previously showed that both cerebrospinal fluid (CSF)
      homovanillic acid (HVA) and 5-hydroxyindole-acetic acid (5-HIAA) concentrations
      are low in pediatric OMS. In this study, we measured levels of CSF Dopa,
      catecholamines, deaminated metabolites of catecholamines, as well as HVA and 5
      HIAA in eight patients before and during treatment with ACTH. All the children
      were ACTH-responsive with 50-70% improvement in multiple clinical features of
      OMS. ACTH treatment reduced the HVA concentration in every child by a mean of 21%
      (p < 0.001). Treatment with ACTH was associated with significant correlations
      between dopaminergic markers such as HVA, dihydroxyphenylacetic acid (DOPAC), and
      Dopa. There were no significant changes in the CSF concentrations of the
      noradrenergic markers norepinephrine (NE) and dihydroxyphenylglycol (DHPG), or
      the serotonergic marker 5-HIAA. The only child with a marked inflammatory pattern
      in CSF, which was reversed by ACTH, was atypical for a large increase in NE and
      decrease in 5-HIAA during ACTH treatment. Beneficial effects of ACTH in OMS are
      not associated with normalization of HVA or 5-HIAA levels. The pattern of
      decreased HVA and unchanged DOPAC levels could reflect decreased extraneuronal
      uptake of catecholamines (which steroids inhibit) or decreased 0-methylation of
      catecholamines in nonneuronal cells.

PMID- 9613747
TI  - Rarity of debrisoquine hydroxylase gene polymorphism in Chinese patients with
      Parkinson's disease.
AB  - Impaired debrisoquine metabolism resulting from defects in the cytochrome P450
      CYP2D6-debrisoquine hydroxylase gene has been shown to be associated with the
      development of Parkinson's disease (PD). We studied two polymorphisms in this
      gene in 207 Chinese PD patients and 227 control subjects by polymerase chain
      reaction and restriction analysis. The G to A substitution at position 1934 in
      the junction of intron 3/exon 4 was detected in one sporadic PD patient and two
      control subjects, all of whom were heterozygous. The single base deletion at
      position 2637 in exon 5 was not detected in any of the study subjects. Such
      rarity of CYP2D6 polymorphism indicates PD in the Chinese population is
      associated with some other gene defects.

PMID- 9613748
TI  - Confirmation of the antidyskinetic effect of posteroventral pallidotomy by means
      of an intraoperative apomorphine test.
AB  - We present a series of six consecutive Parkinson's disease patients undergoing
      posteroventral pallidotomy (PVP), who received an apomorphine injection after
      thermolesioning the posteroventral region of the internal globus pallidus (GPi)
      to evaluate the effect of the lesion on drug-induced dykinesias and therefore to
      proceed with further lesions or to conclude the surgery. Five of six patients
      failed to present dykinesias or did so to a significantly lesser degree (F [2,10]
      42.6; p < 0.0001) so that surgery was concluded. One patient continued having
      contralateral dyskinesia despite an improvement in rigidity and bradykinesia,
      therefore, a new track was performed followed by a new lesion. No differences
      were found between intrasurgical and 1-month postoperative apomorphine test
      values. This report indicates that the use of an apomorphine test after
      thermolesioning may provide a reliable tool to check lesion efficacy on
      dyskinesia. The development of techniques that provide additional clinical
      information to the electrophysiological recording could help improve the outcome
      of patients undergoing pallidotomy.

PMID- 9613749
TI  - Apomorphine-induced penile erections in Parkinson's disease.
AB  - Penile erections were regularly induced by intermittent subcutaneous injections
      of apomorphine in five patients with Parkinson's disease (PD) complicated by
      motor fluctuations. Four of the patients reported erectile dysfunction before
      beginning apomorphine and two of these report a significant improvement in their
      sexual function resulting from apomorphine use. Animal studies suggest central D2
      type dopamine receptor stimulation and oxytocin release from the paraventricular
      nucleus of the hypothalamus mediate the effect. Erections reported with other
      dopamine agonists and levodopa are probably mediated by the same mechanism.
      Apomorphine-induced erections in PD are probably more common than previously
      thought. The benefit of apomorphine on sexual function in some patients suggests
      a possible role in the treatment of impotence in PD.

PMID- 9613750
TI  - Cortical myoclonus in levodopa-responsive parkinsonism.
AB  - We observed myoclonic movements of the fingers and wrists in two patients with a
      levodopa-responsive parkinsonian syndrome most consistent with Parkinson's
      disease. These patients were studied with electrophysiological techniques. Brief
      (<50 ms) myoclonic electromyographic discharges showed a time-locked relationship
      to a focal premovement electroencephalographic potential. Somatosensory-evoked
      potentials were not enlarged and long-latency reflexes were not grossly
      exaggerated. This pattern of electrophysiological findings can be distinguished
      from those previously found in other parkinsonian syndromes. These results
      provide evidence for a cortical origin of the myoclonus seen in these patients.

PMID- 9613751
TI  - Voluntary palatal tremor in two siblings.
AB  - We report two siblings with palatal tremor (PT) and ear clicks who can
      voluntarily elicit or suppress both PT and ear clicks by just "thinking" about
      starting or stopping the sounds. The patients were also able to voluntarily
      modulate the frequency of their ear clicks and PT. They did not have any signs of
      cerebellar, brain stem, or other neurologic disease. These familial palatal
      movements may represent a variant of palatal tremor but can not satisfactorily be
      classified as either symptomatic or essential PT.

PMID- 9613752
TI  - Exteroceptive and interoceptive stimuli in dystonia.
AB  - Some patients with torsion dystonia experience a dramatic increase or decrease in
      symptoms when performing specific activities. The activities that influence
      dystonic symptoms vary from person to person. An activity or sensory stimulus
      that reduces symptoms has been called a "sensory trick" or, in cervical dystonia,
      a "geste antagoniste." When a single activity induces symptoms of dystonia, the
      dystonia is called "task specific." We have discovered that in some patients,
      thinking about a sensory trick or task affects the dystonia in the same way as
      actually performing the activity. We present three representative patients, and
      discuss the relevance of this observation to the understanding of dystonia.

PMID- 9613753
TI  - Extensor truncal dystonia: successful treatment with botulinum toxin injections.
AB  - Patients with truncal extension dystonia, manifested by involuntary back arching,
      often associated with pain and severe motor disability, have not consistently
      responded to pharmacologic agents. We evaluated 4 women and 1 man (mean age, 41.8
      years; dystonia duration, 9.8 years) with severe idiopathic (2 patients) or
      tardive (3 patients) truncal and cervical dystonia. Using electromyographic
      guidance, we injected botulinum toxin into the paravertebral muscles of the
      lumbar region in four to six sites using 25-50 U per site. We reevaluated
      patients 2-4 weeks after injection. The mean dose of botulinum toxin into back
      muscles was 210 U (range, 150-300 U). By blinded videotape evaluation, objective
      improvement was found in three patients with a mean truncal dystonia score
      improving by 37%. Patient evaluation showed improvement in movement ranging from
      20-80% (mean, 46%) after botulinum toxin. In all patients with pain as a result
      of dystonia, there was substantial improvement. None of the patients worsened and
      no adverse effects occurred. Botulinum toxin injections offer a potent new
      treatment for truncal dystonia.

PMID- 9613754
TI  - Progressive pseudobulbar paresis, early choreiform movements, and later rigidity:
      appearance in two sets of dizygotic twins in the same family.
AB  - In a family with two sets of dizygotic twins, three, possibly all four, siblings
      were affected by the same disorder. The parents were unrelated and the illness
      seemed limited to one generation. Onset was in the early to mid-20s with tics and
      choreiform movements, dysarthria, and dysphagia. Two twins had epilepsy. There
      was a marked dyscoordination of bulbar musculature reminiscent of pseudobulbar
      paresis. Involuntary movements were prominent during the first years, but then
      disappeared and were replaced by an akinetic-rigid parkinsonian appearance in the
      late stage. The intellect remained largely intact. Tendon reflexes were reduced.
      Varying degrees of peripheral nerve changes were seen. Two patients died after 22
      24 years from causes indirectly related to the main illness. Marked degenerative
      changes were found in the caudate nucleus and putamen. Acanthocytes in
      significant numbers could not be detected in peripheral blood.
      Lipoproteinelectrophoresis was normal. Creatine kinase levels were moderately
      raised in one patient, normal in the others. Although certain clinical
      resemblances exist with neuroacanthocytosis, the exact nosologic status of the
      disorder has not been determined.

PMID- 9613755
TI  - Olfactory function in restless legs syndrome.
AB  - Restless leg syndrome (RLS) is usually idiopathic but may occur in patients with
      Parkinson's disease (PD). Both respond to dopaminergic medications. Whether these
      disorders share a common pathophysiology is unclear. Because PD is associated
      with a loss of olfactory function, we compared the olfactory function of patients
      with RLS with control and PD patients. Using the University of Pennsylvania Smell
      Identification Test (UPSIT), olfactory function was found to be normal in
      patients with idiopathic RLS and significantly reduced in patients with PD. This
      suggests that the pathophysiology of RLS differs from PD, and that RLS likely is
      not a "forme fruste" or a preclinical sign of PD.

PMID- 9613756
TI  - Treatment of restless leg syndrome with pergolide--an open clinical trial.
AB  - Dopaminergic treatment with levodopa (L-dopa) has been proven as the treatment of
      first choice in patients with restless leg syndrome (RLS). Augmentation of
      symptoms and end-of-dose rebound phenomena under L-dopa/decarboxylase inhibitor
      treatment present major problems in some patients. To evaluate the efficacy of
      pergolide in RLS, we treated 15 patients suffering from severe RLS, who had
      previously experienced an augmentation of symptoms under long-term treatment with
      L-dopa, in an open clinical trial with pergolide. All patients reported an
      improvement of their RLS symptoms. Our study shows that pergolide, if
      administered at a mean dose of 0.4 mg in combination with domperidone, is a very
      effective drug in the treatment of sleep disturbances and daytime symptoms
      associated with RLS, and does not cause any serious side effects during the
      observation period of 6 months.

PMID- 9613757
TI  - Proton MR spectroscopic findings in paroxysmal kinesigenic dyskinesia.
AB  - Although paroxysmal kinesigenic dyskinesia (PKD) has characteristic clinical
      features, the pathophysiology of PKD has remained unknown. The purpose of this
      study was to investigate the pathophysiology of idiopathic PKD by performing
      proton magnetic resonance spectroscopy (1H-MRS) in five patients with idiopathic
      PKD. Three patients were familial and two sporadic. Single-voxel 1H-MRS was
      performed on a GE 1.5-T SIGNA MR system. Localized 1H-MR spectra were obtained
      from the basal ganglia (n = 5), thalamus (n = 3), and supplementary motor area
      (SMA; n = 4) using STEAM sequence (stimulated echo acquisition mode; TR = 3.0
      sec, TE = 30 msec, 64 AVG, volume = 8 mL) or PRESS (point resolved spectroscopy;
      TR = 3.0 sec, TE = 135 msec, volume = 4 mL). Peak ratios of Cho/Cr (Cho: choline,
      Cr: creatine) and mI/Cr (mI: myoinositol) were decreased significantly in the
      unilateral basal ganglia of two patients. In one, decreased peak ratio of mI/Cr
      in the unilateral basal ganglia was the only abnormality. In the remaining two,
      there was no significant abnormality. 1H-MR spectra obtained from the thalamus
      and SMA were all within normal limits. In conclusion, these results suggest that
      underlying pathophysiological mechanism of PKD may be at least partially
      associated with the dysfunction of cholinergic system in the basal ganglia.

PMID- 9613759
TI  - Resurgence of functional neurosurgery for Parkinson's disease: a historical
      perspective.
AB  - The history of functional neurosurgery for the treatment of Parkinson's disease
      is reviewed. Two major stages may be distinguished: (1) open functional
      neurosurgery, which started in 1921 with bilateral cervical rhizotomy by Leriche.
      In 1937 Bucy performed the first motor cortectomy in a tremor patient, and
      subsequently introduced lesioning of the corticospinal tract at different levels.
      In 1939 Meyers started open transventricular surgery of the basal ganglia, which
      was abandoned in the 1940s because of high mortality. However, this operation
      drew attention to the basal ganglia and their efferent pathways as surgical
      targets for the relief of parkinsonian symptoms. (2) Stereotactic (closed)
      functional neurosurgery in patients was in 1947 for the first time performed by
      Spiegel and Wycis, soon followed by surgeons in various countries. Originally,
      the globus pallidus and the ansa lenticularis were the surgical targets but were
      replaced at the end of the 1950s by the ventrolateral thalamus. A few surgeons
      positioned their lesions in the subthalamic area. In both targets favorable
      results were reported for the treatment of tremor and rigidity with acceptable
      adverse events. In selected patients, bilateral surgery was performed. In 1969
      the results of more than 37,000 stereotactic operations had been published.
      Criteria for the surgical technique and selection of patients were described, and
      various stereotaxic atlases became available. At that time, L-dopa became
      generally available and the number of stereotactic operations declined
      dramatically. However, as a result of the shortcomings of the L-dopa therapy in
      the long-term treatment of Parkinson's disease, the thalamotomy gradually
      regained its place. New developments were the reintroduction of the pallidotomy
      by Laitinen in 1992 and the thalamic stimulation for pharmacotherapy-resistant
      tremor by Benabid and collaborators in 1991. New insights in the pathophysiology
      of Parkinson's disease supported the revival of the functional stereotactic
      neurosurgery and recently caused the introduction of the subthalamic nucleus as a
      surgical target in the treatment of Parkinson's disease.

PMID- 9613758
TI  - Erdheim-Chester disease with extensive intraaxial brain stem lesions presenting
      as a progressive cerebellar syndrome.
AB  - We report a rare case of Erdheim-Chester disease (ECD) presenting as a
      progressive cerebellar syndrome and diabetes insipidus. On magnetic resonance
      imaging, a 7-mm extraaxial, enhancing mass was seen enveloping the right
      vertebral artery and was confirmed at autopsy to represent an adventitial
      xanthoma with lipid-laden, foamy histiocytes. The cerebellar syndrome most likely
      resulted from extensive histiocytic infiltration of the pons, particularly the
      basis pontis and middle cerebellar peduncles.

PMID- 9613760
TI  - Severe bilateral tremor in a liver transplant recipient taking cyclosporine.

PMID- 9613761
TI  - Clozapine for dopaminergic-induced paraphilias in Parkinson's disease.

PMID- 9613762
TI  - Extreme anticipation in young-onset Parkinson's disease.

PMID- 9613763
TI  - Parkinsonism following electrical injury to the hand.

PMID- 9613764
TI  - Cortical and brain stem hyperexcitability in striatonigral degeneration.

PMID- 9613765
TI  - Pisa syndrome in a patient with multiple system atrophy.

PMID- 9613766
TI  - Transient syndrome of continuous muscle fiber activity associated with
      staphylococcal infection.

PMID- 9613767
TI  - Intrathecal baclofen in the treatment of dystonic storm.

PMID- 9613768
TI  - Paraneoplastic "rubral" tremor: a case report.

PMID- 9613769
TI  - Clozapine treatment of delayed-onset paroxysmal hemidystonia.

PMID- 9613770
TI  - Blepharospasm associated with bilateral infarcts confined to the thalamus: case
      report.

PMID- 9613771
TI  - Vocal tics in Gilles de la Tourette syndrome treated with botulinum toxin
      injections.

PMID- 9613772
TI  - Postprandial (reactive) hypoglycemia and restless leg syndrome: related
      neurologic disorders?

PMID- 9613773
TI  - Fahr's disease--far from a disease.

PMID- 9613774
TI  - Trimethoprim-sulfamethoxazole and biopterin treatment in Machado-Joseph disease.

PMID- 9613775
TI  - Sertraline for the treatment of depression in Parkinson's disease.

PMID- 9613776
TI  - Mobilization of peripheral blood progenitor cells by disease-specific
      chemotherapy in patients with soft tissue sarcoma.
AB  - We investigated peripheral blood progenitor cell (PBPC) mobilization by disease
      specific chemotherapy in patients with metastatic soft tissue sarcoma (STS). Nine
      patients, five females and four males, aged 12-51 years, pretreated by one to
      nine courses of cytotoxic chemotherapy, underwent STS-specific mobilization
      followed by G-CSF at 5 microg/kg/day. PBPC were collected by 19 conventional
      volume aphereses (8-12 l) with one to four procedures in individual patients.
      Leukaphereses started on median day 15 (range 13-18) from the first day of
      mobilization chemotherapy at medians of 25.8 x 10(3) WBC/microl (6.8-46.9), 3.5 x
      10(3) MNC/microl (1.1-8.8), 122 x 10(3) platelets/microl (72-293) and 30.7 CD34+
      cells/microl (6.7-207.8). Cumulative harvests resulted in medians of 4.6 x 10(8)
      MNC/kg (3.0-6.4), 2.9 x 10(6) CD34+ cells/kg (1.1-11.1) and 12.0 x 10(4) CFU
      GM/kg (2.0-37.8). Eight patients underwent high-dose chemotherapy (HDCT) followed
      by PBPC rescue. Seven patients recovered hematopoiesis at medians of 12 days (8
      15) for ANC >0.5 x 10(3)/microl and 14 days (8-27) for platelets >20 x
      10(3)/microl. One patient, who received 1.6 x 10(6) CD34+ cells/kg, exhibited
      delayed ANC recovery on day +37 and failed to recover platelets until hospital
      discharge on day +55. We conclude that in patients with metastatic STS, who are
      pretreated by standard chemotherapy, PBPC can be mobilized by a further course of
      STS-specific chemotherapy plus G-CSF. One to four conventional-volume aphereses
      result in PBPC autografts that can serve as hematopoietic rescue for patients
      scheduled for HDCT.

PMID- 9613777
TI  - Blast counts in blood progenitor cell (BPC) correlate with CD34+ cells and CFU-GM
      and are useful predictor of haemopoietic recovery after autologous BPC
      transplantation collections.
AB  - Assessment of the quality of blood progenitor cell (BPC) collections is based
      mainly on CD34+ cell enumeration by flow cytometry, or scoring of granulocyte
      macrophage colony-forming cells (CFU-GM). A minimum cell dose for haemopoietic
      recovery can be defined by both assays; however, the CFU-GM assay can not be used
      for 'real-time' decisions, whereas CD34+ cell scoring requires facilities and
      expertise which are not universally available. We have investigated the
      possibility of using morphologically defined blast cells within BPC harvests as a
      surrogate marker of harvest haemopoietic stem/progenitor cell content, as well as
      their correlation with CD34+ cells and CFU-GM within the harvests. We have found
      that blast counts correlate strongly with both CD34+ cell counts and CFU-GM
      within BPC harvests, as well as with time to granulocyte and platelet recovery
      after autologous BPC transplantation (ABPCT). Furthermore, we have defined a
      threshold value of 1.3 x 10(6)/kg blasts, above which there is a high probability
      of rapid haemopoietic recovery after ABPCT. We conclude that blast count is a
      simple, rapid and reliable method of assessing BPC harvest quality.

PMID- 9613778
TI  - Combination chemotherapy with mitoguazon, ifosfamide, MTX, etoposide (MIME) and G
      CSF can efficiently mobilize PBPC in patients with Hodgkin's and non-Hodgkin's
      lymphoma.
AB  - Many centers use CY and G-CSF to mobilize PBPC. In this study we explored whether
      a standard chemotherapy regimen consisting of mitoguazon, ifosfamide, MTX and
      etoposide (MIME) combined with G-CSF was capable of mobilizing PBPC in lymphoma
      patients. Twelve patients with Hodgkin's disease (HD) and 38 patients with non
      Hodgkin's lymphoma (NHL) were mobilized with MIME/G-CSF. Most patients were
      heavily treated with different chemotherapy regimens receiving a median of 11
      cycles (range 3 to 20) of chemotherapy prior to mobilization. It was found that
      the optimal time of PBPC harvest was at days 12 and 13 after initiating the
      mobilization regimen. The median number of collected CD34+ cells per kg body
      weight was 7.1 x 10(6) (range 0.5-26.2). More than 2.0 x 10(6) CD34+ cells/kg
      were achieved in 69% of the patients after one apheresis. When additional cycles
      of apheresis were done, only 6% failed to harvest this number of CD34+ cells.
      There was a statistically significant inverse correlation between the number of
      prior chemotherapy cycles and CD34+ cell yield (P = 0.003). No such association
      was found between CD34+ cell yield and prior radiotherapy. When MIME/G-CSF was
      compared with Dexa-BEAM/G-CSF, it was found that MIME/G-CSF tended to be more
      efficient in mobilizing PBPC in spite of being less myelotoxic. All patients
      transplanted with MIME/G-CSF mobilized PBPC had fast and sustained engraftment.
      These results demonstrate that an ordinary salvage chemotherapy regimen, such as
      MIME combined with G-CSF can be successfully used to mobilize PBPC.

PMID- 9613779
TI  - Toxicity, pharmacology and feasibility of administration of PEG-L-asparaginase as
      consolidation therapy in patients undergoing bone marrow transplantation for
      acute lymphoblastic leukemia.
AB  - We attempted to administer PEG-L-asparaginase (PEG-L-A) following hematologic
      recovery to 38 patients undergoing autologous or allogeneic marrow
      transplantation for acute lymphoblastic leukemia (ALL). Twenty-four patients (12
      of 22 receiving allogeneic and 12 of 16 receiving autologous transplants)
      received between one and 12 doses of PEG-L-A, including nine who completed the
      planned 12 doses of therapy. The toxicities encountered were similar to those
      observed in non-transplanted patients undergoing therapy with PEG-L-A and
      included allergic reactions, pancreatitis, weight loss, hypoalbuminemia, and low
      levels of anti-thrombin III. Of the 24 who received the drug, eight remain in
      remission. Of 12 patients in second remission at the time of transplantation who
      received PEG-L-A, five of seven who received allogeneic and two of five who
      received autologous transplants remain in remission, 16+ to 46+ months from
      transplant. While PEG-L-A could be administered to most of the patients
      undergoing marrow transplantation for ALL, most patients either relapsed while
      receiving the drug or developed toxicities which resulted in abbreviated courses.
      At this time, we cannot recommend PEG-L-A as single agent, post-BMT chemotherapy.

PMID- 9613780
TI  - Salvage autologous or allogeneic transplantation for multiple myeloma refractory
      to or relapsing after a first-line autograft?
AB  - Forty-two patients allografted for multiple myeloma after not having attained at
      least a partial remission (n = 19) or after having experienced disease
      progression (n = 23) following one autograft were compared with 42 pair-matched
      controls who underwent salvage autotransplantation under identical conditions.
      Autografted controls were matched closely for albumin, C-reactive protein,
      creatinine, disease sensitivity, duration of standard therapy prior to the first
      transplant, Ig isotype, karyotype, LDH, and response to the first transplant,
      but, in comparison to allografted patients, were older, had higher beta2
      microglobulin, and had a shorter interval between the two transplants. The
      complete remission rate was 41% after allogeneic and 33% after autologous
      transplantation (P = NS). The 3-year probability of event-free survival was
      comparable for the two groups (25 +/- 8% after autografting and 20 +/- 8% after
      allografting). The 3-year probability of survival was significantly higher after
      autologous transplantation (54 +/- 8% vs 29 +/- 9%; P = 0.01). Twenty-one
      patients in the autograft group were alive 11-59 months (median 32) following the
      second transplant, while 15 patients in the allograft group were alive at 10-53
      months (median 20). The 3-year probability of disease progression was
      significantly lower after allogeneic transplantation (31 +/- 10% vs 72 +/- 9%, P
      = 0.03). The 1-year probability of transplant-related mortality was significantly
      higher after allografting (43 +/- 8% vs 10 +/- 5%; P = 0.0001). We conclude that
      while autografting appears to be superior to allografting for salvage therapy of
      myeloma persisting or relapsing after one previous autotransplant in terms of
      overall survival, event-free survival is comparable due to significantly lower
      disease progression after allografting. Reduction in allograft-related toxicity
      can potentially improve the results of allogeneic transplantation significantly.

PMID- 9613781
TI  - T cell-depleted allogeneic bone marrow transplantation for high-risk non
      Hodgkin's lymphoma: clinical and molecular follow-up.
AB  - The use of allogeneic BMT in patients with relapsed non-Hodgkin lymphoma (NHL)
      offers the advantage of tumor-free bone marrow and possibly a 'graft-versus
      lymphoma effect' which may decrease the risk of recurrence. However, allogeneic
      BMT also poses an increased risk of death due to graft-versus-host disease (GVHD)
      which can be ameliorated by T cell depletion. We performed a retrospective review
      of 37 patients who underwent T cell-depleted allogeneic BMT for aggressive and
      indolent NHL between 1988 and 1996. Polymerase chain reaction (PCR) was used to
      identify indolent NHL patients with the BCL2/IgH translocation which served as a
      marker of residual disease. Sixteen of 37 patients (44%) are alive and
      progression-free with a median follow-up of 4.4 years (range 1-10.3). The
      incidence of grade 2-4 acute GVHD was 36% and extensive chronic GVHD developed in
      12%. Patients with aggressive NHL have an overall PFS of 33% (12-54%); those with
      chemotherapy-resistant and sensitive disease have PFS of 17% (0-47%), and 40% (15
      65%) respectively at 5 years. Patients with indolent histologies have overall PFS
      of 62% (37-86%); those with chemotherapy-resistant and sensitive disease have PFS
      of 55% (25-85%) and 80% (45-100%) respectively at 5 years. Eight patients with
      indolent disease had a BCL2/IgH translocation detectable by PCR. Five of these
      eight patients remain alive and progression free at a median of 6.5 years after
      BMT (range 2.1-7.4 years), four of whom remain PCR positive from 1.7 to 2.9 years
      after transplantation. We conclude that T cell-depleted allogeneic BMT poses a
      low risk for death due to GVHD, and should be considered for patients with
      relapsed and refractory indolent NHL.

PMID- 9613782
TI  - Cyclosporin A-induced graft-versus-host disease following autologous bone marrow
      and stem cell transplantation in hematological malignancies of childhood.
AB  - Cyclosporin A (CsA) can induce graft-versus-host disease (GVHD) following
      autologous bone marrow transplantation (ABMT) and autologous peripheral blood
      stem cell transplantation (APBSCT) in adults. We investigated whether GVHD can be
      induced following ABMT and APBSCT in childhood, and which cells are involved in
      the pathogenesis of this syndrome. We conducted a prospective study of 20
      children and adolescents with hematological malignancies receiving CsA after ABMT
      and APBSCT. Skin biopsies were obtained on day 21 after transplantation or in the
      event of a rash. Immunophenotypic analysis of peripheral blood lymphocytes was
      performed on days 14, 21, 28 and 60 after transplantation. Clinical GVHD of the
      skin, confirmed by histological criteria, occurred in five patients. Five
      patients had no clinical GVHD but had acute GVHD alterations on routine skin
      biopsy. In all 10 patients with a positive skin biopsy for GVHD, CD4+ lymphocytes
      were the predominant cells in the epidermis. Immunophenotypic analysis of
      peripheral blood lymphocytes revealed a significantly increased CD4/CD8 ratio in
      patients with a positive skin biopsy (P < 0.01). Our findings indicate that it is
      possible to induce acute GVHD following ABMT and APBSCT in childhood. In
      addition, CD4+ lymphocytes play an important role in the pathogenesis of CsA
      induced GVHD.

PMID- 9613783
TI  - Assessment and characterization of the cytolytic T lymphocyte response against
      Epstein-Barr virus in patients with non-Hodgkin's lymphoma after autologous
      peripheral blood stem cell transplantation.
AB  - The cytolytic T lymphocyte (CTL) response has often been used to assess the
      reconstitution of T cell function after allogeneic or autologous bone marrow
      transplantation (BMT). Less is known, however, about the reconstitution of the
      CTL response after peripheral blood stem cell transplantation (PBSCT). Therefore,
      we investigated the CTL response against Epstein-Barr virus (EBV) of patients
      undergoing autologous PBSCT. CTLs of six patients with relapsed non-Hodgkin's
      lymphoma and multiple myeloma were established before and at different times
      after PBSCT by in vitro stimulation of peripheral blood lymphocytes with
      autologous EBV-transformed lymphoblastoid cell lines (LCLs). The efficiency of T
      cell priming by LCLs was assessed at the time of initiation of CTL lines; the
      proliferative response was strongly reduced during the first 4 months and
      increased 5 months or more following PBSCT. Cytolytic activity was measured after
      three or four restimulations of CTLs. All patients investigated had a detectable
      EBV-specific CTL response which was poor during the first weeks after
      transplantation, accompanied by a strong non-MHC-restricted cytotoxic activity
      and a high proportion of CD56-positive T cells. Five or more months after PBSCT,
      a specific CTL response against EBV was seen which was similar to the situation
      prior to PBSCT, while the unspecific cytotoxic response decreased. Blocking
      experiments with monoclonal anti-CD3, anti-CD8 or anti-MHC I antibodies resulted
      in substantial inhibition of autologous LCL lysis, whereas anti-CD4 or anti-MHC
      II antibodies had no effect. Finally, autologous PHA blasts of a patient with the
      HLA haplotype A1/9+, B5/8+, Cw4/7+, were loaded with various EBNA-derived
      nonapeptides known to be presented by HLA B8 or A11, and exposed to autologous,
      EBV-directed CTLs. Specific lysis by CTLs only occurred with HLA B8-, but not
      with HLA A11-restricted nonapeptides. This demonstrated the existence of an MHC I
      restricted anti-EBV CTL response after PBSCT. Taken together, the results show
      that the anlaysis of the EBV-directed CTL activity may serve as a surrogate
      marker to assess the reconstitution of the cellular immune response in patients
      undergoing autologous PBSCT.

PMID- 9613784
TI  - Comparison of an enzyme immunoassay and a latex agglutination system for the
      diagnosis of invasive aspergillosis in bone marrow transplant recipients.
AB  - The performance of two Aspergillus antigenemia systems, the sandwich enzyme
      linked immunosorbent assay (ELISA), Platelia Aspergillus test, and the latex
      agglutination (LA), Pastorex Aspergillus test, in the diagnosis of invasive
      aspergillosis were compared by testing 364 serum samples from 22 bone marrow
      transplant (BMT) recipients. Sensitivity and specificity for the ELISA test were
      60% and 82% respectively, vs 40% and 94% for the LA test. In the two patients
      found positive with both methods, the ELISA test became positive earlier than the
      LA test or remained positive after the LA test had become negative. These results
      encourage further evaluation of the Platelia Aspergillus test, to assess its role
      in the management of invasive aspergillosis in BMT patients.

PMID- 9613785
TI  - Analysis of the value of empiric vancomycin administration in febrile neutropenia
      occurring after autologous peripheral blood stem cell transplants.
AB  - We conducted a retrospective review of 125 patients undergoing high-dose therapy
      and stem cell rescue in order to evaluate the incidence of documented infection
      and the utility of the administration of vancomycin empirically. All patients
      received prophylactic oral quinolone therapy. Because neutropenia in this setting
      is relatively brief, 21 patients never manifested fever, and no patient died of
      infection. Of the remaining 104 patients, positive blood cultures were obtained
      in only 10, nine with a gram stain positive and one with a gram stain negative
      organism. Sixty-two patients without any evidence of gram positive infection
      received vancomycin according to the existing algorithm for care of neutropenic
      fevers. In this population of patients, empiric administration of vancomycin for
      neutropenic fevers without culture documentation appears to be unnecessary, could
      be discontinued safely and at substantial cost savings, and might slow the
      appearance of vancomycin-resistant organisms.

PMID- 9613786
TI  - Reduced charges and costs associated with outpatient autologous stem cell
      transplantation.
AB  - High-dose chemotherapy and stem cell rescue is increasingly being delivered in
      the outpatient setting. Such intensive outpatient management programs have
      reduced the total hospital length of stay without compromising clinical outcomes.
      However, a detailed financial analysis of outpatient programs has not been
      performed. These data are the results of a prospective study of 94 patients
      receiving high-dose chemotherapy and autologous peripheral blood stem cell
      transplant in one of three settings: traditional inpatient, partial outpatient,
      total outpatient. Patients were allowed to choose their own treatment setting
      based upon the availability of a caregiver and personal preference. Total
      hospital length of stay and the actual cost and charges for each patient were
      monitored prospectively. The patients in the three groups were well balanced with
      regard to age and functional status prior to high-dose chemotherapy. The average
      length of stay was reduced from 17.3 to 8.2 to 2.7 days in the three different
      treatment settings (P < 0.01). Mean procedure costs were reduced from $39.7
      thousand (US dollars) to $36.2 thousand to $29.4 thousand in the three treatment
      settings (P < 0.029). No differences in toxicity or overall response to therapy
      was noted. High-dose chemotherapy and stem cell rescue can be safely administered
      in the outpatient setting and results in significant cost savings.

PMID- 9613787
TI  - Comparison of CD34+ bone marrow cells purified by immunomagnetic and
      immunoadsorption cell separation techniques.
AB  - We tested two positive selection techniques for separation of CD34+ cells from
      bone marrow and analyzed the yields of CD34+ cells, BFU-E, CFU-GM, CFU-MK and LTC
      IC after selection and expansion. An immunoadsorption procedure (CellPro) and an
      immunomagnetic (Baxter) CD34+ cell separation method were employed to purify the
      same bone marrow samples from seven normal subjects. Mean yields of CFU-GM and
      CFU-MK and absolute numbers of LTC-ICs were not different in the two purified
      cell populations. In contrast, the mean recovery of BFU-E was significantly lower
      for the immunoadsorption (21 +/- 14%) than for the immunomagnetic technique (44
      +/- 27%). After separation, CD34+ cells were evaluated in 10-day liquid cultures
      for their expansion capacity in terms of total cells and progenitors. The
      expansion capacity of progenitors such as CFU-GM, CFU-MK and especially BFU-E
      selected by immunoadsorption was higher than the capacity of progenitors obtained
      by immunomagnetism, although final total and progenitor cell numbers are similar.
      Our results suggest that the populations separated by the two techniques differ
      mainly in the expansion capacity of progenitors and in the recovery of BFU-E
      after the selection procedure. These differences between two methods, which
      already are widely employed in research and in clinical transplantation, should
      be taken into account when considering the aims of the experiments.

PMID- 9613788
TI  - Fatal obstructive lung disease after haploidentical sibling cord blood
      transplantation.
AB  - We report the case of a patient with fatal obstructive lung disease after an HLA
      haploidentical sibling cord blood transplant (CBT), with severe acute GVHD. A 2
      year-old girl developed expiratory air trapping gradually with acute and chronic
      GVHD after CBT for the treatment of ALL. Anti-CMV and immunosuppressive therapy
      were ineffective, and the patient died of progressive respiratory acidosis.
      Necropsy of the lung revealed severe bronchiolitis obliterans with cytomegalic
      inclusion cells in the granulation tissues of the bronchiolitis. Thus,
      immunologic and GVHD problems can occur even in CBT.

PMID- 9613789
TI  - Prolonged remission and autologous recovery in two patients with chronic
      myelogenous leukemia after graft failure of allogeneic bone marrow
      transplantation.
AB  - Two patients with Philadelphia-positive chronic myelogenous leukemia underwent
      allogeneic bone marrow transplantation from a related HLA mismatched donor
      (patient 1) or from an unrelated HLA-identical donor (patient 2). Following bone
      marrow transplantation partial engraftment (patient 1) or graft failure (patient
      2) occurred followed by autologous Philadelphia negative hematopoietic recovery
      either spontaneously (patient 1) or after infusion of autologous bone marrow
      rescue (patient 2). Neither Philadelphia chromosome, nor bcr-abl rearrangement
      was detectable by PCR analysis up to 7 years (patient 1) and 9 years (patient 2)
      post-transplantation. These two observations indicate that sustained engraftment
      of allogeneic bone marrow stem cells following a myeloablative regimen is not
      necessary to cure chronic myelogenous leukemia. It is hypothesized that the
      proliferative advantage of Philadelphia-negative progenitors and the anti
      leukemic effect of lymphocytes in the graft have resulted in prolonged remission
      of the patients.

PMID- 9613790
TI  - Hepatic veno-occlusive disease with severe capillary leakage after peripheral
      stem cell transplantation: treatment with recombinant plasminogen activator and
      C1-esterase inhibitor concentrate.
AB  - Severe veno-occlusive disease (VOD), characterised by elevated serum bilirubin
      levels, is a known complication in the first 3 weeks after peripheral blood stem
      cell transplantation (PBSCT). Severe VOD is associated with capillary leakage and
      multiple organ dysfunction and leads to high mortality. We report a 17-year-old
      male, who developed VOD with capillary leakage (CL) after allogeneic PBSCT. The
      patient presented with a maximum serum bilirubin of 25.4 mg/dl, weight gain (10%
      of baseline weight), generalized edema, cardiovascular insufficiency, complement
      activation, jaundice and a decreased AT and protein C functional activity. After
      VOD and CL were diagnosed the patient was treated with recombinant human
      plasminogen activator (rt-PA) and C1 esterase-inhibitor concentrate (C1-INH-C).
      The clinical symptoms resolved and the patient's status stabilized. The patient
      was in an adequate clinical state 5 months after transplantation. We noted that
      the combined therapy with rt-PA and C1-INH-C in this high-risk situation led to a
      resolution of VOD with CL.

PMID- 9613791
TI  - Bronchiolitis obliterans organizing pneumonia and ulcerative colitis after
      allogeneic bone marrow transplantation.
AB  - A 37-year-old man with acute myeloblastic leukemia in first remission developed
      ulcerative colitis and bronchiolitis obliterans organizing pneumonia (BOOP) 7
      months after bone marrow transplantation (BMT) from an HLA-matched brother who
      suffered from severe Crohn's disease. BOOP occurred 20 days after idiopathic
      interstitial pneumonia, in the context of severe ulcerative colitis. Lung and
      colon biopsies showed no signs of CMV infection or GVHD. The patient was treated
      with oral methylprednisolone 1 mg/kg/day and his clinical status and chest X-ray
      improved slowly. Remarkably, the symptoms of colitis also resolved with
      prednisone therapy and he is now symptom-free. We hypothesize that ulcerative
      colitis may have been transmitted from donor to recipient (adoptive autoimmunity)
      and that it was complicated by BOOP. However, other factors such as CMV may have
      contributed to the occurrence of BOOP.

PMID- 9613792
TI  - Achievement of complete cytogenetic remission after two very low-dose donor
      leucocyte infusions in a patient with extensive cGVHD relapsing in accelerated
      phase post allogeneic BMT for CML.
AB  - We report the case of a 55-year-old female who despite having developed extensive
      chronic graft-versus-host disease (GVHD), relapsed 35 months after a T cell
      replete sibling donor bone marrow transplant for Philadelphia-positive chronic
      myeloid leukaemia (Ph CML). She achieved complete cytogenetic remission after
      discontinuation of cyclosporin A and administration of two low-dose donor
      leucocyte infusions (DLI 1 x 10(6) and 5 x 10(6) CD3+ cells/kg). Eighteen months
      after the first infusion she remains well and in complete cytogenetic remission
      with a normocellular marrow and no exacerbation of GVHD.

PMID- 9613793
TI  - Successful autologous transplantation in a patient with severe aplastic anemia
      (SAA).
AB  - We report a patient who underwent peripheral blood hematopoietic progenitor
      (PBHP) autologous transplantation for his third SAA relapse. Although his
      repeated relapses were always successfully reversed by immunosuppression, he
      developed anaphylaxis with horse, rabbit and mouse immunoglobulins as a side
      effect of his previous treatment. He was mobilized with G-CSF and underwent three
      leukaphereses in the period of hematologic recovery after the second relapse.
      Fourteen months later, he suffered his third relapse, rescued by autologous PBHP
      transplantation after cyclophosphamide and melphalan conditioning. At present he
      is 15 months after transplantation without any treatment, transfusion-independent
      and in good condition. Others have published the observation that sufficient PBHP
      can be collected at least in some patients with SAA. Our experience shows that in
      repeatedly relapsing SAA with no other treatment options autologous
      transplantation with previously collected PBHP can result in successful
      hematologic reconstitution.

PMID- 9613794
TI  - Benefit of aggressive multimodality therapy with autologous stem cell support for
      intra-abdominal desmoplastic small round cell tumor.
AB  - A case is described of a 19-year-old man with poor prognosis intra-abdominal
      desmoplastic small round cell tumor, who achieved a durable complete remission
      after aggressive multimodality treatment. He was diagnosed with a large peri
      rectal mass and bulky metastases to the peritoneum, omentum and liver. He
      achieved a partial response to six courses of chemotherapy with VAC (vincristine,
      adriamycin, actinomycin, cyclophosphamide) and VIP (VP-16, ifosfamide,
      cisplatin). This was followed by resection of the omentum and cryotherapy to six
      of the liver lesions. He then achieved a complete response following high-dose
      busulfan 16 mg/kg and melphalan 140 mg/m2 with autologous stem cell support.
      Finally, pelvic radiotherapy was given to consolidate the remission. Twenty-six
      months following his diagnosis, and 19 months after the transplant, he remains
      well with no clinical or radiologic evidence of recurrent disease. This case
      report suggests a role for autologous stem cell transplantation as part of
      multimodality therapy for this unusual and aggressive malignancy.

PMID- 9613795
TI  - Bone marrow transplant in Diamond-Blackfan anemia.

PMID- 9613796
TI  - Acute gouty arthritis following recombinant human granulocyte colony-stimulating
      factor therapy in an allogeneic blood stem cell donor.

PMID- 9613797
TI  - Pattern of autonomic dysfunction in time course of complex regional pain
      syndrome.
AB  - The objective of the present investigation was to describe and localize autonomic
      dysfunction in acute and chronic stages of complex regional pain syndrome (CRPS).
      Patients were investigated twice: the first investigation was performed as soon
      as diagnosis was established during the acute stage of CRPS and the second
      investigation was performed about 2 years later. Twenty-one patients completed
      the follow-up investigation. The median duration of CRPS was 5 (range 2-21) weeks
      at first investigation and 94 weeks (22-148) at follow-up. Skin temperature was
      recorded by thermography, sudomotor function was assessed by thermoregulatory
      sweat test (TST) and quantitative sudomotor axon reflex test (QSART). Skin
      temperature was warmer on the affected side at the first investigation (P <
      0.001) and colder at follow-up (P < 0.02) compared with the contralateral limb.
      Sudomotor output was enhanced after both TST (P < 0.005) and QSART (P < 0.05) at
      the first investigation on the affected side. However, at follow-up, sweating
      after TST was still increased (P < 0.04) while QSART responses were not different
      between the affected and unaffected limbs. As compared to controls there was no
      statistically significant difference, neither in skin temperature nor sweating,
      neither on the affected nor on the unaffected side. In conclusion, the present
      investigation proved that vasomotor and sudomotor control are substantially
      altered in CRPS. In the acute stage vasomotor control is decreased in the
      affected limb whereas sudomotor function is enhanced. This may be the result of
      disturbances of thermoregulation, but different secondary peripheral mechanisms,
      concerning vasomotor and sudomotor function, contribute to clinical presentation
      of CRPS and affect autonomic function at all stages of CRPS.

PMID- 9613798
TI  - The effect of noradrenaline, angiotensin II and vasopressin on blood flow and
      sensitivity to heat in capsaicin-treated skin.
AB  - The effect of iontophoretically applied noradrenaline, angiotensin II and
      vasopressin on blood flow and sensitivity to heat was investigated in the
      capsaicin-treated forearms of 52 healthy volunteers. Non-specific effects of a 4
      min saline iontophoresis were investigated in another 19 subjects. Pretreatment
      with phentolamine inhibited vasoconstriction and thermal hyperalgesia to
      noradrenaline, indicating that alpha-adrenoceptors mediated these responses. The
      intensity of thermal hyperalgesia differed significantly across the following
      treatments: saline (heat pain threshold 1.1 degrees C lower than at control
      sites), angiotensin II (3.4 degrees C), noradrenaline (6.4 degrees C) and
      vasopressin (9.0 degrees C). Decreases in skin blood flow were significantly
      greater after the iontophoresis of noradrenaline (65% reduction from baseline)
      and vasopressin (68%) than after the iontophoresis of angiotensin II (45%). In
      contrast to the other two drugs, angiotensin II induced thermal hyperalgesia in
      proportion to the intensity of vasoconstriction. The findings suggest that
      iontophoretic currents induce minor non-specific thermal hyperalgesia.
      Angiotensin II appears to increase sensitivity to heat by an ischaemic mechanism,
      whereas an additional non-vascular influence contributes to thermal hyperalgesia
      induced by noradrenaline and vasopressin. These mechanisms could contribute to
      hyperalgesia in chronic inflammatory or neuropathic pain syndromes.

PMID- 9613799
TI  - Relative burst amplitude in human muscle sympathetic nerve activity: a sensitive
      indicator of altered sympathetic traffic.
AB  - Microneurographically recorded sympathetic outflow to the human muscle vascular
      bed is traditionally quantified by identifying pulse-synchronous bursts of
      impulses in a mean voltage neurogram and expressing them in terms of bursts per
      minute (burst frequency) or bursts per 100 heart beats (burst incidence). As both
      these measures show large inter-individual differences in resting healthy
      subjects, a problem arises when comparing sympathetic traffic in cross-sectional
      studies, making moderate differences in muscle sympathetic nerve activity (MSA)
      between groups difficult to identify. Absolute measures of the strength of the
      sympathetic discharges (burst amplitude or area) can also be evaluated. However,
      as they critically depend on the proximity of the microelectrode to the recorded
      fibres, such measures cannot be used for interindividual comparisons. The aim of
      the present study was to evaluate the use of relative burst amplitude spectra for
      quantification of MSA, describing the proportion of small vs large bursts in a
      neurogram. We recorded MSA in 18 patients with mild to moderate congestive heart
      failure (CHF) (New York Heart Association functional classes I-IIIA) and 18
      matched healthy controls. Sympathetic activity was expressed as burst frequency,
      burst incidence and burst amplitude spectra. When comparing the traditional burst
      counts between the groups (presented as the median and 25th-75th percentiles)
      there was a tendency towards higher MSA in CHF patients, but the difference was
      not significant (42 (34-52) vs 53 (41-63) bursts/min, 62 (51-78) vs 69 (52-84)
      bursts/100 heart beats, both ns). Relative burst amplitude spectra, on the other
      hand, were clearly shifted to the right in the CHF group compared to the control
      group (median burst amplitudes 42 (34-45) vs 30 (28-35), P = 0.0002). Relative
      burst amplitude spectra thus appear to provide a more sensitive indicator of
      altered MSA than traditional burst counts. The right-ward shift of these spectra
      may suggest that sympatho-excitation occurs early in the development of CHF.

PMID- 9613800
TI  - Effects of exposure to simulated microgravity on neuronal catecholamine release
      and blood pressure responses to norepinephrine and angiotensin.
AB  - We tested the hypothesis that exposure to microgravity reduces the neuronal
      release of catecholamines and blood pressure responses to norepinephrine and
      angiotensin. Eight men underwent 30 days of 6 degrees head-down tilt (HDT)
      bedrest to simulate exposure to microgravity. Plasma norepinephrine and mean
      arterial blood pressure (MAP) were measured before and after a cold pressor test
      (CPT) and graded norepinephrine infusion (8, 16 and 32 ng/kg/min) on day 6 of a
      baseline control period (C6) and on days 14 and 27 of HDT. MAP and plasma
      angiotensin II (Ang-II) were measured during graded Ang-II infusion (1, 2 and 4
      ng/kg/min) on C8 and days 16 and 29 of HDT. Baseline total circulating
      norepinephrine was reduced from 1017ng during the baseline control period to 610
      ng at day 14 and 673ng at day 27 of HDT, confirming a hypoadrenergic state. An
      elevation of norepinephrine (+178 ng) to the CPT during the baseline control
      period was eliminated by HDT days 14 and 27. During norepinephrine infusion,
      similar elevations in plasma norepinephrine (7.7 pg/ml/ng/kg/min) caused similar
      elevations in MAP (0.12 mmHg/ng/kg/min) across all test days. Ang-II infusion
      produced higher levels of plasma Ang-II during HDT (47.3 pg/ml) than during
      baseline control (35.5 pg/ml), while producing similar corresponding elevations
      in blood pressure. While vascular responsiveness to norepinephrine appears
      unaffected, impaired neuronal release of norepinephrine and reduced vascular
      responsiveness to Ang-II might contribute to the lessened capacity to
      vasoconstrict after spaceflight. The time course of alterations indicates effects
      that occur within two weeks of exposure.

PMID- 9613801
TI  - Baroreceptor sensitivity response to phase IV of the Valsalva maneuver in spinal
      cord injury.
AB  - Due to the increased prevalence of ischemic heart disease and hypertension
      reported in individuals with chronic spinal cord injury (SCI), we investigated
      whether subjects with low level SCI (paraplegia), without apparent evidence of
      coronary artery disease, exhibit normal baroreceptor and autonomic function.
      Eighteen males participated in this study: seven normotensive with paraplegia,
      five hypertensive with paraplegia and six normotensive non-SCI controls. The
      Valsalva maneuver was performed by maintaining a pressure of 40 mmHg over 15 s
      and R-R intervals (RRI) and arterial blood pressure were measured continuously.
      Phase IV of the Valsalva maneuver was determined by linear regression analysis
      between RRI and systolic pressure, with a final slope calculated. The power
      spectra for RRI and blood pressure variability parameters were also analyzed, in
      addition to the index alpha, a frequency domain estimate of the overall gain in
      baroreceptor control of the RRI-arterial blood pressure. The normotensive
      subjects with paraplegia were found to have an impaired baroreceptor response
      when compared with age-matched, non-SCI controls. In addition, the levels of both
      the low frequency and high frequency spectral components of RRI and the index
      alpha were reduced in these individuals at rest. These cumulative findings
      strongly suggest that the integrity of the sinoaortic baroreceptors, as well as
      efferent parasympathetic function, may be compromised in otherwise apparently
      healthy individuals with chronic paraplegia.

PMID- 9613802
TI  - The role of delayed orthostatic hypotension in the pathogenesis of chronic
      fatigue.
AB  - Past studies have shown that severe fatigue was the presenting symptom in six of
      seven patients with delayed orthostatic hypotension and that tilt table-induced
      hypotension was found in 22 of 23 patients with the chronic fatigue syndrome. We
      have determined the prevalence of fatigue, volunteered in response to a
      nonspecific pre-examination questionnaire used in 431 patients, each subsequently
      diagnosed as having one of eight neurological or endocrine disorders. The results
      show that fatigue is a very common symptom in patients with delayed orthostatic
      hypotension (n = 21), as well as both primary (n = 30) and secondary (n = 106)
      hypocortisolism: 70-83% in all groups. In contrast, fatigue was an uncommon
      complaint in patients with multiple system atrophy (MSA) (n = 30), pituitary
      disorders without hypocortisolism (n = 106) or idiopathic hirsutism (n = 96): 7
      33% in all groups, and was intermediate in prevalence in patients with acute
      hyperadrenergic orthostatic hypotension (n = 32): 41%. It is concluded that
      fatigue commonly results from delayed orthostatic hypotension and all forms of
      hypocortisolism but is less common in patients with acute orthostatic
      hypotension, both idiopathic and due to MSA, which more commonly present with
      lightheadedness or syncope.

PMID- 9613804
TI  - Topographical control of cells.
AB  - We review the literature on the reaction of cells to their surrounding
      topography. The topography may be that of surrounding cells, intercellular
      materials or biomaterials. The reactions include cell orientation, rates of
      movement, and activations of the cells. We concentrate on those papers where
      quantitative measurements of the reactions have been made and largely ignore
      those on subjective impressions. A wide range of topographies are considered but
      special attention is given to results on groove-ridge topographies. The question
      of whether the cells are reacting to the topography directly or to patterned
      substratum chemistry formed on the topography is discussed. The review ends with
      a summary of the types of prosthesis where advantage has been taken of the
      ability to fabricate topography.

PMID- 9613803
TI  - Autonomic neurotoxicity of jellyfish and marine animal venoms.
AB  - Venoms and poisons of jellyfish and other marine animals can induce damage to the
      human nervous and circulatory systems. Clues to the pathogenesis and clinical
      manifestations of these lesions can be obtained from data of human envenomations
      and animal experimentation. Because many investigators are unaware that marine
      animal venoms have autonomic actions, this paper aims to elucidate the broad
      antagonistic or toxic effects these compounds have on the autonomic nervous
      system. Marine venoms can affect ion transport of particularly sodium and
      calcium, induce channels or pores in neural and muscular cellular membranes,
      alter intracellular membranes of organelles and release mediators of
      inflammation. The box jellyfish, particularly Chironex fleckeri, in the Indo
      Pacific region, is the world's most venomous marine animal and is responsible for
      autonomic disorders in patients. The symptoms induced by these venoms are
      vasospasm, cardiac irregularities, peripheral neuropathy, aphonia, ophthalmic
      abnormalities and parasympathetic dysautonomia. Cases of Irukandji syndrome,
      caused by the jellyfish Carukia barnesi, have symptoms that mimic excessive
      catecholamine release. Coelenterate venoms can also target the myocardium,
      Purkinje fiber, A-V node or aortic ring. Actions on nerves, as well as skeletal,
      smooth or cardiac muscle occur. Recent studies indicate that the hepatic P-450
      enzyme family may be injured by these compounds. The multiplicity of these venom
      activities means that a thorough understanding of the sting pathogenesis will be
      essential in devising effective therapies.

PMID- 9613805
TI  - Effect of C4-, C8- and C18-alkylation of poly(vinyl alcohol) hydrogels on the
      adsorption of albumin and fibrinogen from buffer and plasma: limited correlation
      with platelet interactions.
AB  - Polyvinyl alcohol (PVA) hydrogel was partially alkylated with short (C4),
      intermediate (C8) and long (C18) alkyl chains to test the hypothesis that an
      alkylated surface might promote enhanced interaction with albumin and thus
      exhibit low platelet thrombogenicity. PVA hydrogel was reacted with alkyl halides
      (C4, C8 or C18) and coated onto polyethylene. The effect of surface alkylation
      (extent of alkylation and alkyl chain length) on the adsorption of human serum
      albumin and fibrinogen to these surfaces was investigated in both buffer and
      plasma. Platelet interactions were investigated in vitro using flow cytometry
      methods. The maximum surface concentrations of albumin and fibrinogen adsorbed
      from buffer onto PVA and alkylated PVA were characteristic of monolayers. At low
      concentrations differences in adsorption among the surfaces appeared to be
      related to hydrophobicity as determined by dynamic advancing water contact angle,
      and to degree of alkylation as determined by angle dependent XPS analysis. Alkyl
      chain length dependence was not observed. Adsorption from plasma was considerably
      lower than from buffer, except for albumin on C8-PVA where monolayer adsorption
      was observed. Fibrinogen adsorption from plasma was similar on PVA, C8-PVA and
      C18-PVA, but was higher on C4-PVA. For albumin adsorption from plasma, the
      initial slope of the adsorption-concentration curve was highest for C18-PVA,
      suggesting higher albumin affinity despite the low degree of substitution of the
      C18-PVA material. These data suggest possible selectivity of the C18 alkylated
      PVA for albumin. Platelet studies showed that C4-PVA was the least platelet
      reactive (microparticle generation and P-selectin expression) of the alkyl
      derivatized materials.

PMID- 9613806
TI  - Protein denaturation induced by cyclic silicone.
AB  - While it has been demonstrated that such low-molecular-weight cyclic silicones as
      octamethylcyclotetrasiloxane (D4) exhibit adjuvant activity, the mechanism of
      immunological response to silicone is still not clear. This study therefore used
      fluorescence and circular dichroism (CD) spectroscopy to investigate the
      denaturation and conformational change of two proteins, fibronectin (Fn) and
      fibrinogen (Fbg), induced by D4 in vitro. Incubating D4 with Fbg or Fn at D4-to
      protein ratios of > 100 or for > 10 h yielded white and mould-like precipitates
      of the proteins, indicating massive denaturation and aggregation. The fact that
      the decrease in fluorescence intensity of D4-treated Fn and Fbg was accompanied
      by a red shift in the maximum wavelength also indicated that denaturation of the
      proteins had taken place. These changes in fluorescence might result from
      exposure of tryptophan residuals in the proteins to polar water molecules
      inasmuch as the denaturation would lead to changes in the tertiary structures of
      the proteins and rearrangement of the tryptophan residues. The loss of the
      tertiary structure leads to protein denaturation and, consequently,
      precipitation. The difference in CD spectra between control Fbg (or Fn) and D4
      treated Fbg (or Fn) indicated conformational changes of the proteins when
      incubated with D4. Thus it has been demonstrated that D4 can induce denaturation
      and conformational changes in Fbg and Fn and it can be expected that protein
      molecules that have undergone denaturation or conformational change induced by D4
      may act as antigens and stimulate the immune system to generate antibodies,
      ultimately resulting in autoimmune disease.

PMID- 9613807
TI  - Erosion of biodegradable block copolymers made of poly(D,L-lactic acid) and
      poly(ethylene glycol).
AB  - Biodegradable block copolymers made of poly(ethylene glycol) monomethylether
      (Me.PEG) and poly(D,L-lactic acid) (PLA) were investigated for their erosion
      properties. Wide angle X-ray diffraction (WAXD) and differential scanning
      calorimetry (DSC) investigations prior to erosion revealed that despite the low
      content of crystallizable Me.PEG of 10%, Me.PEG5-PLA45 is a partially crystalline
      polymer. The erosion of the polymer was investigated using cylindrical polymer
      matrix discs with a diameter of 8 mm and a height of 1.5 mm. WAXD and DSC spectra
      obtained from eroded polymer matrix discs suggest that both polymer blocks
      separate completely during erosion. The crystallinity of Me.PEG5-PLA45 was found
      to increase during erosion, which is probably due to the improved mobility of
      Me.PEG inside the polymer with a progressive degree of degradation. The erosion
      kinetics were found to be similar to that of PLA or poly(lactic-co-glycolic
      acid). During erosion the polymer matrix weight of dried samples remains constant
      for 11 weeks after which erosion sets in rapidly. From this observation one can
      conclude that the impact of the relatively small Me.PEG chains on Me.PEG5-PLA45
      erosion is not pronounced. This is beneficial for all those applications that
      require the stability of the polymer matrix and in which the Me.PEG chain is
      intended to bring about other effects such as the modification of the surface
      properties of PLA polymers.

PMID- 9613808
TI  - Corrosion analysis of NiCu and PdCo thermal seed alloys used as interstitial
      hyperthermia implants.
AB  - Ferromagnetic materials with low Curie temperatures are being investigated for
      use as interstitial implants for fractionated hyperthermia treatment of prostatic
      disease. Previous investigations of the system have utilized alloys, such as
      NiCu, with inadequate corrosion resistance, requiring the use of catheters for
      removal of the implants following treatment or inert surface coatings which may
      interfere with thermal characteristics of the implants. We are evaluating a
      palladium-cobalt (PdCo) binary alloy which is very similar to high palladium
      alloys used in dentistry. Electrochemical corrosion tests and immersion tests at
      37 degrees C for both NiCu and PdCo alloy samples in mammalian Ringer's solution
      were performed. Long-term corrosion rates are 5.8 x 10(-5) microm per year (NiCu)
      and 7.7 x 10(-8) microm per year (PdCo) from average immersion test results,
      indicating higher corrosion resistance of PdCo (P < 0.02); immersion corrosion
      rates were much lower than initial corrosion rates found electrochemically. Both
      alloys had significantly lower corrosion rates than standard surgical implant
      rates of 0.04 microm per year (P < 0.001 for both alloys). Scanning electron
      microscopy illustrates changes in the NiCu alloy surface due to pitting
      corrosion; no difference is observed for PdCo. The data indicate that the PdCo
      alloy may be suitable as a long-term implant for use in fractionated
      hyperthermia.

PMID- 9613809
TI  - Response of macrophages to poly(L-lactide) particulates which have undergone
      various degrees of artificial degradation.
AB  - This investigation looked at the effects of artificially degraded poly(L-lactide)
      particles on macrophages in vitro. The effects of very-low-molecular-weight
      unprocessed poly(L-lactide) and poly(glycolide) particles were also examined.
      There were no obvious trends in the data, suggesting that as the artificially
      degraded particles became more degraded, they became more or less toxic.
      Comparisons of the effects of low-molecular-weight poly(L-lactide) and
      poly(glycolide) particles did not reveal any differences between the effects of
      poly(L-lactide) particles and poly(glycolide) particles on cells in vitro. It is
      possible that the reason for this is that the cell line used here is less
      sensitive to particles than cultures of primary cells. Given this information and
      the fact that poly(glycolide) particles have been associated with osteolytic and
      inflammatory problems, this would suggest that further research into poly(L
      lactide) implant degradation would be worthwhile.

PMID- 9613810
TI  - Enhancement of cell interactions with collagen/glycosaminoglycan matrices by RGD
      derivatization.
AB  - The interaction of three cell types important to the wound repair process with
      collagen/glycosaminoglycan (GAG) dermal regeneration matrices covalently modified
      with an Arg-Gly-Asp (RGD)-containing peptide was characterized. Function-blocking
      monoclonal antibodies directed against various integrin subunits were used to
      demonstrate that human fibroblasts attached to the unmodified matrix through the
      integrin, alpha2beta1. Human endothelial cells and human keratinocytes, however,
      attached minimally to the unmodified matrix. After modification of the
      collagen/GAG matrix with RGD-containing peptide, endothelial cells and
      keratinocytes attached and spread well on the matrix. This attachment was RGD
      dependent as evidenced by essentially complete inhibition with competing soluble
      peptide. In terms of overall cell number, fibroblast cell attachment remained
      unchanged on the RGD peptide-modified matrix compared to the unmodified material.
      Antibody and peptide inhibition studies demonstrate, however, that attachment to
      the modified matrix was mediated by both alpha2beta1 and RGD-binding integrins.
      We have successfully introduced a specific RGD receptor-mediated attachment site
      on collagen/GAG dermal regeneration matrices, resulting in enhanced cell
      interaction of important wound healing cell types. This modification could have
      important implications for the performance of these matrices in promoting dermal
      regeneration.

PMID- 9613811
TI  - Randomness and biospecificity: random copolymers are capable of biospecific
      molecular recognition in living systems.
AB  - Biospecific molecular recognition in living systems is known to be based on the
      lock and key principle as proposed by Emil Fischer. Based on this concept,
      biospecific polymers have been produced synthetically by attaching biospecific
      'keys' to the polymer chain. We postulate that biospecificity can be achieved by
      alternative means, namely random substitution of a preformed polymer with
      suitable chemical groups or random copolymerization of suitable functional
      monomers. Such polymers, we suggest, will contain arrangements of the chemical
      functions which mimic natural biospecific sites and the probability of occurrence
      of such arrangements will depend on the average composition of the polymer. In
      support of this principle, we have developed several functional random copolymer
      systems which possess a variety of biological properties depending on the type of
      chemical function. Examples are: polymers possessing anticoagulant properties
      similar to those of heparin; polymers which interact specifically with components
      of the immune system; and polymers which, in contact with cells, affect their
      growth and metabolism. In the case of statistical copolymers possessing 'DNA
      like' properties obtained by phosphorylation of hydroxylated polystyrene
      derivatives, Monte Carlo simulations were used to determine the distribution of
      phosphodiester (PDE) groups along the chains and to compute the probabilities of
      occurrence of particular arrangements of PDE found in the 'DNA-like' sites. The
      results showed that these sites are made up of PDE groups separated by distances
      that closely match those between the same groups along a generatrix of the DNA
      double-helix cylinder. These findings offer the prospect of manufacturing
      polymeric biomaterials endowed with biomimetic character. Moreover, they provide
      the basis for a hypothesis regarding the appearance of biospecificity at the
      origin of life, suggesting that biospecific structures may have evolved by
      natural selection from purely random copolymers. It is likely therefore that
      biospecificity is a continuous function of randomness, arising from purely
      statistical distributions of reactivity and evolving into precisely defined
      structures such as those involved in ligand-receptor interactions.

PMID- 9613812
TI  - Controlled delivery of therapeutics from microporous membranes. II. In vitro
      degradation and release of heparin-loaded poly(D,L-lactide-co-glycolide).
AB  - In vitro degradation and release of five types of heparin/surfactant-loaded
      poly(D,L-lactide-co-glycolide 50:50) (PLG) microspheres alone and also
      incorporated within microporous polyurethane tubes were studied over a 3-month
      period. Degradation was studied with scanning electron microscopy (SEM), Fourier
      transform infrared spectroscopy (FTIR), gel permeation chromatography (GPC) and
      differential scanning calorimetry (DSC). Heparin release was characterized using
      a modified Azure A assay. SEM suggests that microspheres may be entrapped within
      polyurethane fibrils of the polyurethane tubes, thereby reducing contact with
      their hydrated environment. FTIR transmittance spectra confirm microsphere
      incorporation within the polyurethane tubes and PLG ester hydrolysis occurring
      over the 3-month period. A correlation was observed between decreasing molecular
      weights and glass transition temperatures (Tg). The microspheres alone exhibited
      a change in Tg but not when incorporated within the microporous tubes. Release
      profiles revealed a burst effect occurring during the first 4h and total release
      of the heparin from the microspheres by 12 weeks.

PMID- 9613813
TI  - High-pressure infrared and FT-Raman investigation of a dental composite.
AB  - Composite resins are often used as filling materials on load-bearing surfaces of
      teeth. As masticatory stresses can be high, here, we study the effect of pressure
      on the behaviour of a dental composite. Using a polymerized wafer, the IR and FT
      Raman spectra of a zirconia-containing proprietary composite (Z100, 3M,
      Minneapolis, MN, USA) were recorded. The high-pressure IR spectra were also
      recorded. Band assignments were made for the main peaks of both organic and
      inorganic components. Breaks in the pressure dependences (dv/dP) of the organic
      components were found at 22 kbar. Different pressure dependences for different
      vibrational modes of inorganic components were also observed. These data suggest
      that the network structure of the composite is compacted under high pressure and
      that both the atomic distance and bonding angles in the network are altered.

PMID- 9613814
TI  - Validation of a small punch testing technique to characterize the mechanical
      behaviour of ultra-high-molecular-weight polyethylene.
AB  - The small punch or miniaturized disc bend test has been used successfully to
      characterize the ductility and fracture resistance of metals and ceramics with
      specimens measuring 0.5 mm in thickness. This study was performed to demonstrate
      the feasibility of performing small punch tests on implant grade ultra-high
      molecular-weight polyethylene (UHMWPE). Large-deformation finite element
      simulations were developed and validated to explore the hypothesis that the
      macroscopic constitutive behaviour of UHMWPE may be inferred from a miniature
      specimen testing technique which can be used to characterize the ductility and
      work to failure for UHMWPE. The load-displacement curve was insensitive to cyclic
      preconditioning of the test specimen and only mildly sensitive to the loading
      rate. Furthermore, the initial slope of the small punch load-displacement curve
      was used to determine the elastic modulus of the UHMWPE with the help of the
      inverse finite element method. The ultimate goal of this research is to develop
      the capability to perform local measurements of material tensile and static
      fracture properties in as-manufactured, as-sterilized and as-retrieved UHMWPE
      components.

PMID- 9613816
TI  - Solubility of compositions in the system CaTi(x)Zr4-(x)(PO4)6 with x = 0-4.
AB  - In vitro solubility tests of granulated materials and coatings were carried out
      on some compositions in the system CaTi(x)Zr4-(x)(PO4)6 with x = 0-4, in order to
      find a biocompatible material which is less soluble than hydroxyapatite (HA) and
      can also be used as bone substitution material. The granulated materials were
      leached out by using circulating equipment in which the solvent flows in
      circulation. The coatings were tested under conditions where the sample
      containers undergo a circular movement. The results show better chemical
      stability of nearly all tested compounds compared with HA for both granulated
      materials and coatings.

PMID- 9613815
TI  - Biocompatible, glucose-permeable hydrogel for in situ coating of implantable
      biosensors.
AB  - A glucose-permeable hydrogel (97% water by mass) was formed by cross-linking an 8
      armed, amine-terminated poly(ethylene glycol) (PEG) derivative with a di
      succinimidyl ester of an alpha,omega-dipropionic acid derivative of PEG in
      aqueous solution at room temperature. The gel was evaluated as a biocompatible
      interface between an amperometric glucose electrode and the subcutaneous tissue
      of a rat. Over a glucose concentration range of 0-30 mM, the loss in sensitivity
      to glucose caused by the application of the hydrogel was 34% and the reduction in
      limiting current at high glucose concentration (30 mM) was 35% at 37 degrees C
      for films that were approximately 0.06 mm thick, an acceptable loss. Hydrogel and
      Pellethane samples were subcutaneously implanted in male Sprague-Dawley rats for
      7 days. The explanted samples were thin-sectioned, stained and examined under a
      light microscope. While the Pellethane samples were encapsulated with tissue
      consisting of macrophages, neutrophils, foreign body giant cells, fibroblasts and
      collagen, the PEG samples had very few adherent cells. The results show this
      system to be a good candidate for providing biocompatible interfaces for sensors,
      especially oxidoreductase-based sensors.

PMID- 9613817
TI  - The microstructure of ultra-high molecular weight polyethylene used in total
      joint replacements.
AB  - The microstructure of ultra-high molecular weight polyethylene (UHMWPE) has been
      studied using a range of techniques. Both the unprocessed base powder and ram
      extruded polymer have been examined using optical microscopy, scanning and
      transmission electron microscopy and small-angle light scattering. By examining
      the microstructure of samples compression moulded at a range of temperatures,
      techniques have been developed to assess the degree of consolidation of the
      processed polymer. The raw polymer is a powder with a particle size in the range
      50-250 microm. These particles are themselves agglomerates of much finer
      particles typically 0.5-1 microm in size. It has been suggested that these sub
      micron particles may be the origin of the sub-micron wear debris found in tissues
      around total joint replacements. However, examination of the ram-extruded
      polymer, from which implants are machined, shows a different structure from the
      powder, with no evidence of retention of the 0.5-1 microm structure seen in the
      powder in the processed material. It thus appears that the similarity in size
      between the sub-micron wear debris particles and the fine structure seen in the
      unprocessed UHMWPE resin is coincidental. Processed UHMWPE does show a 'memory'
      of the grain boundaries between powder particles and the degree of consolidation
      can be assessed by observing the distinctiveness of these boundaries.

PMID- 9613818
TI  - A retrospective and prospective view of glycopathology.

PMID- 9613819
TI  - Perspectives in the glycosciences--matrix-assisted laser desorption/ionization
      (MALDI) mass spectrometry of carbohydrates.

PMID- 9613820
TI  - Rapid analysis of O-acetylated neuraminic acids by matrix assisted laser
      desorption/ionization time-of-flight mass spectrometry.
AB  - N-Acetylneuraminic acid (a sialic acid) occurs mainly as a terminal substituent
      of oligosaccharides of glycoconjugates. Derivatives of neuraminic acid occur
      widely, substituted in the amino and hydroxy side chains, as well in the C-9
      carbon skeleton. These derivatives are responsible for specific functions of
      sialic acids during cell-cell, cell-substrate, or cell-virus interactions. The
      study of O-acetylated neuraminic acids is difficult, because only small amounts
      are extractable from natural sources and they are generally unstable to acids and
      bases. We report a new method for the rapid analysis of O-acetylated neuraminic
      acids, using a combination of reversed phase HPLC and MALDI-TOF mass
      spectrometry. A mixture of neuraminic acids from bovine submaxillary gland mucins
      was analysed, as well as neuraminic acids variously substituted in the amino and
      hydroxy side chains with acetyl and glycolyl groups, respectively.

PMID- 9613821
TI  - New sialyltransferase inhibitors based on CMP-quinic acid: development of a new
      sialyltransferase assay.
AB  - Quinic acid (4) was transformed into phosphitamides 6, 14, and 15, which could be
      readily linked to 5'-O-unprotected cytidine derivative 7; ensuing oxidation of
      the obtained phosphite triesters with tert-butylhydroperoxide furnished the
      corresponding phosphate triesters 8, 16, and 17, respectively. Hydrogenolytic
      debenzylation of the phosphate moiety, base catalysed removal of acetyl
      protective groups, and basic hydrolysis of the methylester of the quinic acid
      moiety furnished CMP-Neu5Ac analogues 1-3. In order to measure their inhibition
      of sialyltransferases, a nonradioactive sialyltransferase assay [employed for
      alpha(2-6)-sialyltransferase from rat liver (EC 2.4.99.1)] based on reversed
      phase HPLC separation of UV-labelled acceptor 20 (p-nitrophenyl glycoside of N
      acetyllactosamine) from the UV-labelled product 21 (p-nitrophenyl glycoside of
      sialyl alpha(2-6')-N-acetyllactosamine) and p-nitrophenylalanine as internal
      standard was developed. The assay reproduced the reported K(M) values for CMP
      Neu5Ac and N-acetyllactosamine and the Ki values for CDP. 1 and 2 turned out to
      be potent sialyltransferase inhibitors.

PMID- 9613822
TI  - Strict order of (Fuc to Asn-linked GlcNAc) fucosyltransferases forming core
      difucosylated structures.
AB  - In insect cells fucose can be either alpha1,6- or alpha1,3-linked to the
      asparagine-bound GlcNAc residue of N-glycans. Difucosylated glycans have also
      been found. Kinetic studies and acceptor competition experiments demonstrate that
      two different enzymes are responsible for this alpha1,6- and alpha1,3-linkage of
      fucose. Using dansylated acceptor substrates a strict order of these enzymes can
      be established for the formation of difucosylated structures. First, the alpha1,6
      fucosyltransferase catalyses the transfer of fucose into alpha1,6-linkage to the
      non-fucosylated acceptor and then the alpha1,3-fucosyltransferase completes the
      difucosylation.

PMID- 9613823
TI  - Structures of the N-linked sugar chains in the PAS-6 glycoprotein from the bovine
      milk fat globule membrane.
AB  - The structures of the N-linked sugar chains in the PAS-6 glycoprotein (PAS-6)
      from the bovine milk fat globule membrane were determined. The sugar chains were
      liberated from PAS-6 by hydrazinolysis, and the pyridylaminated sugar chains were
      separated into a neutral (6N) and two acidic chains (6M and 6D), the acidic sugar
      chains then being converted to neutral sugar chains (6MN and 6DN). 6N was
      separated into two neutral fractions (6N13 and 6N5.5), while 6MN and 6DN each
      gave a single fraction (6MN13 and 6DN13). The structure of 6N5.5, which was the
      major sugar chain in PAS-6, is proposed to be Man alpha1 --> 6 (Man alpha1 --> 3)
      Man beta1 --> 4GlcNAc beta1 --> 4GlcNAc-PA; 6N13, 6MN13 and 6DN13 are proposed to
      be Gal beta1 --> 3Gal beta1 --> 4GlcNAc beta1 --> 2Man alpha1 --> 6 (Gal beta1 -
      > 3Gal beta1 --> 4GlcNAc beta1 --> 2Man alpha1 --> 3) Man beta1 --> 4GlcNAc beta1
      --> 4 (Fuc alpha1 --> 6)GlcNAc-PA; 6M and 6D had 1 or 2 additional NeuAc residues
      at the non-reducing ends of 6MN13 and 6DN13, respectively.

PMID- 9613824
TI  - Structure of the O-glycopeptides isolated from bovine milk component PP3.
AB  - The heat-stable acid-soluble phosphoglycoprotein component PP3 was isolated from
      the bovine milk proteose peptone fraction by concanavalin A affinity
      chromatography. Glycopeptides from the ConA-bound fraction corresponding to the
      component PP3 were obtained by Pronase digestion and were separated by gel
      filtration into high and low-molecular-mass glycopeptides. In a previous work, we
      have investigated the structure of the N-glycans from the high-molecular-mass
      glycopeptides [Girardet et al. (1995) Eur J Biochem 234: 939-46]. Here, we
      describe the structure of the O-glycans from the low-molecular-mass
      glycopeptides. By combining methylation analysis, mass spectrometry, 400 MHz 1H
      NMR spectroscopy and peptide sequence analysis, we show that the low-molecular
      mass fraction contains several neutral glycopeptides. A mixture of the following
      three glycan structures linked to the Thr86 has been identified: GalNac alpha1-O
      Thr, Gal(beta1-3)GalNAc alpha1-O-Thr and Gal(beta1-4)GlcNAc(beta1-6)[Gal(beta1
      3)]GalNAc alpha1-O-Thr.

PMID- 9613825
TI  - alpha1,3 Fucosyltransferase, alpha-L-fucosidase, alpha-D-galactosidase, beta-D
      galactosidase, and Le(x) glycoconjugates in developing rat brain.
AB  - Fucosyltransferases (FTs) and various glycosidases that are involved in the
      biosynthesis or degradation of SSEA-1 (Le(x)) antigens and their precursors in
      the CNS are developmentally regulated. In forebrain and cerebellum with
      lactosamine (LacNAc) as acceptor the FT activity was maximal at P15-P22, but with
      the glycolipid substrate paragloboside (nLc4) the maximal activity in cerebellum
      was obtained at P10-P15. The FT activity, with these substrates, was insensitive
      to N-ethylmaleimide (NEM) and the glycolipid product had an alpha1,3 linkage (Fuc
      to GlcNAc) suggesting similarities of the investigated enzyme to the cloned human
      and rat FT IV. However, the observation of different patterns of FT activity in
      isoelectrofocused fractions (pH 3.5-10) with different types of acceptors, and
      the differential expression of Le(x) containing glycolipids and glycoproteins
      during development strongly suggest the presence of more than one type of FT
      during development. Data on developmental expression of the hydrolytic enzymes,
      alpha-L-fucosidase, beta-D-galactosidase and alpha-D-galactosidase, which can
      potentially hydrolyse SSEA-1 or its precursors, support the notion that SSEA-1
      expression is the result of a dynamic balance between the activity of
      transferases and hydrolases.

PMID- 9613826
TI  - Sialyl Lewis(x) epitopes do not occur on acute phase proteins in mice:
      relationship to the absence of alpha3-fucosyltransferase in the liver.
AB  - Mice are frequently used in models for the study of immunological processes
      related to inflammation. Since it is known that the degree of fucosylation of
      human acute phase proteins (APPs) is altered as a consequence of an inflammatory
      response, we have undertaken this study to gain more insight into the
      fucosylation of acute phase proteins as it occurs in mouse liver. Mice carrying
      the cluster of the three genes encoding human alpha1-acid glycoprotein (AGP), one
      of the well known APPs, were used and the fucosylation of AGP was assessed. A
      complete absence of fucosylation on the transgenic human AGP was found, which is
      in sharp contrast to AGP in human serum, of which a major proportion is normally
      alpha3-fucosylated. Remarkably, a large proportion of mouse AGP did contain
      fucose residues. Fucosylation was also detected on another APP, mouse protease
      inhibitor (PI). Alpha3-fucosylation of the transgenic human AGP can be achieved
      in vitro, using an alpha3/4-fucosyltransferase (alpha3/4-FucT) isolated from
      human milk, showing that the glycoprotein is not intrinsically resistant to
      fucosylation. Upon subsequent measurement of the activities of the possible
      fucosyltransferases present in liver membranes of parent and transgenic mice,
      only an N-linked-core alpha6-FucT and no alpha2-, alpha3- or alpha4-FucT activity
      was detected. This indicates that fucose residues found on the mouse serum
      proteins AGP and PI, which are synthesized in the liver, are most probably in
      alpha6-linkage to the core chitobiosyl unit. Interestingly, both alpha6- and
      alpha3-FucT activity was detectable in human liver membranes. None of the above
      mentioned findings were influenced by the induction of an acute phase response by
      administration of bacterial lipopolysaccharide. This study shows that: (a) alpha6
      FucT is probably a protein specific-glycosyltransferase, since mouse AGP, but not
      human AGP, may be used as an acceptor; (b) in contrast to human liver, mouse
      liver does not express any alpha3-FucT-activity, thereby making the mouse
      incapable of producing the Sialyl Lewis(x) epitope on APPs, which is an important
      part of the inflammatory reaction in humans. This last finding indicates that the
      mouse is not suitable as a model for the study of those phenomena related to
      inflammation in humans, in which glycosylation of acute phase proteins could play
      a significant role.

PMID- 9613827
TI  - Immunohistochemical study on a macrophage calcium-type lectin in mouse embryos:
      transient expression in chondroblasts during endochondral ossification.
AB  - We investigated expression of mouse macrophage galactose/N-acetylgalactosamine
      specific calcium-type lectin (MMGL) in mouse embryos using a rat monoclonal
      antibody (mAb) LOM-14 that we previously developed. Immunoblot analysis revealed
      that a significant expression of MMGL was first detected in detergent extracts of
      whole embryos of 11 days post coitus (dpc) and the level of its expression
      increased during further fetal development (examined up to 18-dpc embryos).
      Tissue sections of 12, 14, 16, and 18-dpc embryos, newborn and adult mice were
      investigated by immunohistochemical staining. In embryos of 12-dpc and later
      stages, mesenchymal cells (typically distributed in the embryonic skin) exhibited
      positive signals for MMGL. Interestingly, a conspicuous staining was observed
      during endochondral ossification in temporary cartilage tissue, in which
      chondroblasts were transiently positive for MMGL. The staining intensity for the
      chondroblasts peaked in 14-dpc embryos and then gradually decreased. The staining
      was diminished while hypertrophy and maturation of chondrocytes proceeded, and
      was eliminated in areas with calcification. Immunoelectron microscopic study
      demonstrated the presence of MMGL in rough endoplasmic reticulum in the
      chondroblasts in the temporary cartilage tissue in 14-dpc embryos. These results
      provide first evidence showing the expression of MMGL in cells other than
      macrophages.

PMID- 9613829
TI  - MMC and LD simulations of alpha-D-Glcp-(1-->2)-alpha-D-Glcp-(1-->3)-alpha-D-Glcp
      OMe. A model for the terminal trisaccharide in glycoprotein precursors.
AB  - The conformational flexibility and the dynamics of alpha-D-Glcp-(1-->2)-alpha-D
      Glcp(1-->3)-alpha-D-Glcp-OMe (I) has been investigated by Metropolis-Monte Carlo
      with the HSEA (Hard Sphere Exo-Anomeric) force field and Langevin dynamics
      simulations employing two different CHARMm (Chemistry at HARvard Molecular
      Mechanics) force fields, CHEAT95 and PARM22. The conformational space spanned by
      the molecule is similar for the two former force fields but differ significantly
      for the latter. Hydrogen bonding between O2" and O4 of the title compound is
      analysed in comparison to NMR and preliminary results from X-ray powder
      diffraction studies.

PMID- 9613828
TI  - Stimulation as well as inhibition by antibiotics of the formation of GlcNAc
      lipids of the dolichol pathway.
AB  - The antiobiotics, diumycin, amphomycin, bacitracin, and showdomycin have been
      shown previously to block the synthesis of GlcNAc-P-P-dolichol and GlcNAc-GlcNAc
      P-P-dolichol. In view of inconsistencies in the literature concerning the sites
      of inhibition, we have reinvestigated the influence of these drugs on the
      formation of these early intermediates of the dolichol pathway. Unexpectedly,
      when the individual products of the reactions were examined, instead of
      inhibition, showdomycin and bacitracin were found to stimulate the formation of
      GlcNAc-P-P-dolichol, and diumycin stimulated at low concentrations. Three
      derivatives of showdomycin were examined with similar results, showing
      stimulations of GlcNAc-P-P-dolichol formation of up to two-fold over controls.
      Amphomycin specifically inhibited GlcNAc-P-P-dolichol formation, an effect that
      was reversed by a high concentration of dolichyl phosphate. In contrast, with the
      exception of amphomycin, each compound directly inhibited the formation of GlcNAc
      GlcNAc-P-P-dolichol. Using chemically synthesized GlcNAc-P-P-dolichol as
      substrate, the kinetics of inhibition of GlcNAc-GlcNAc-P-P-dolichol formation by
      showdomycin, bacitracin and diumycin was examined. The apparent Ki values
      calculated from these studies indicated that showdomycin was the most active
      inhibitor. These findings provide a new understanding of the action of these
      compounds on the GlcNAc-transferases of the dolichol pathway.

PMID- 9613830
TI  - Interactions of putative heparin-binding domains of basic fibroblast growth
      factor and its receptor, FGFR-1, with heparin using synthetic peptides.
AB  - We have examined structure-function relationships that have been proposed to
      account for the heparin-binding properties of basic fibroblast growth factor and
      its receptor, FGFR-1, using synthetic peptides, DNA synthesis assays and binding
      assays in a resonant mirror biosensor. The results suggest that the interaction
      of FGFR-1 with heparin may not be physiologically relevant and that the site of
      interaction of the polysaccharide on bFGF is more complex than has been
      anticipated.

PMID- 9613831
TI  - C-series polysialogangliosides are expressed on stellate neurons of adult human
      cerebellum.
AB  - Until now 'c-series' polysialogangliosides were known to exist in human brain
      only during development and in some pathological conditions like Alzheimer's
      disease. Using thin-layer chromatography (TLC) and immunostaining with Q211
      antibody (TLC-overlay technique) we have analysed 'c-series' gangliosides in four
      human cerebella (age 20, 47, 52 and 54 years). Four distinct ganglioside bands,
      most probably corresponding to GT1c, GQ1c, GP1c and GH1c were found to exist in
      the analysed brains, which is convincing demonstration of the existence of 'c
      series' gangliosides in normal adult human brain. Immunohistochemical analysis
      was performed to locate polysialogangliosides in the analysed tissue. Q211
      antibody was found to bind specifically to a single subpopulation of neurons in
      the molecular layer of adult cerebellum. According to their position and
      morphology these cells correspond to stellate neurons.

PMID- 9613833
TI  - Native phytotherapy among the Raute tribes of Dadeldhura district, Nepal.
AB  - The herbal drugs used by the Raute tribe of far-western Nepal are discussed. A
      total of 47 species of plants including one species of pteridophyte, four
      monocotyledons and 42 dicotyledons, and 17 types of diseases treated, have been
      identified from this study. Medicinal uses of 15 species (31%) are unrecorded
      from other parts of the country.

PMID- 9613832
TI  - Effects of Anchusa strigosa root aqueous extract on gastric ethanol-induced ulcer
      in laboratory animals.
AB  - Anchusa strigosa Banks et Sol (Boraginaceae) root extracts (ASRE) were prepared
      by soaking the dry material in boiling water. The clear soluble extract was dried
      and found to be 0.238 g/g dry roots. A gastric ulcer was induced in fastened
      animals by oral ingestion of ethanol. Administration of 0.080 g of ASRE prior to
      ethanol ingestion protected the stomach of the rat from ulcer formation. The
      ulcer index values, expressed as a percentage of total stomach surface area
      affected by the ulcer, were lowered from 34.0+/-4.0 to 6.0+/-0.7 and 32.5+/-9.4
      to 2.2+/-1.4 by the morphometric and the planimetric methods, respectively.
      Treatment of the induced ulcer in guinea pigs was achieved by oral administration
      of ASRE at the therapeutic dose of extract of 0.286 g/kg body weight/day for 24
      days. The intraperitoneal LD50 of ASRE in mice was 0.080 g extract/kg body
      weight. Replacing water intake by ASRE at 75 ml of variable extract
      concentrations of 2.865, 3.57 and 4.284 g/l per animal per day for 90 days showed
      no histopathological changes in all organs of the rat. However, a clear
      depression effect on the central nervous system and anemia were observed
      particularly with extract of 3.57 g/l or more.

PMID- 9613834
TI  - Antihepatotoxic activity of monomethyl fumarate isolated from Fumaria indica.
AB  - Monomethyl fumarate, isolated for the first time from the methanolic extract of
      the whole plant of Fumaria indica, was characterised and screened for its
      antihepatotoxic activity in albino rats. The compound showed significant (P <
      0.01) antihepatotoxic activity against thioacetamide in vitro, and against
      hepatotoxicities induced by carbon tetrachloride, paracetamol and rifampicin in
      vivo to an extent almost similar to that of silymarin, a known antihepatotoxic
      agent.

PMID- 9613835
TI  - Nicotine induced inhibition of the activities of accessory reproductive ducts in
      male rats.
AB  - Adult male albino rats were treated with 0.4 mg nicotine/100 g body weight either
      orally or intraperitoneally for 30 days. All animals were autopsied on the 31st
      day. Epididymis and vas deferens were dissected out, weighed and processed for
      biochemical estimations. Nicotine caused a reduction in the weight of epididymis
      and vas deferens in both drug treated groups. The total cholesterol content is
      increased while protein, DNA and RNA contents and the epididymal sperm count were
      decreased. The acid phosphatase content is also decreased, whereas alkaline
      phosphatase is increased. The surface epithelial cell height of these ducts is
      decreased and secretory activity is reduced with the disruption of epithelial
      cell projections. These changes may be due to non-availability of androgens in
      nicotine treated rats.

PMID- 9613836
TI  - Composition of eye cosmetics (kohls) used in Oman.
AB  - A total of 47 kohl samples, primarily used as traditional eye cosmetics, were
      analyzed using X-ray powder diffraction (XRPD) and scanning electron microscopy
      (SEM). It was found that, of the 18 Omani-made kohls, the main component of five
      was galena (PbS). Of the other 13, 12 were based on amorphous carbon and one on
      hematite (Fe2O3). The remaining samples were made in other countries and were
      found to contain one of the following as the main component: galena, minium
      (Pb3O4), amorphous carbon, magnetite (Fe3O4), zincite (ZnO), calcite (CaCO3) or
      sassolite (H3BO3).

PMID- 9613837
TI  - Immunocontraceptive activity guided fractionation and characterization of active
      constituents of neem (Azadirachta indica) seed extracts.
AB  - A novel approach for immunocontraception by intervention of local cell mediated
      immunity in the reproductive system by using single intrauterine application of
      neem oil has been described earlier. The reversible block in fertility was
      reported to last for 107-180 days in female Wistar rats (Upadhyay et al., 1990.
      Antifertility effects of neem oil by single intrauterine administration: A novel
      method of contraception. Proceedings Of The Royal Society Of London B 242, 175
      180) and 7-11 months in monkeys (Upadhyay et al., 1994. Long term contraceptive
      effects of intrauterine neem treatment (IUNT) in bonnet monkeys: An alternative
      to intrauterine contraceptive devices. Contraception 49, 161-167). The present
      study, describes the identification and characterization of the biologically
      active fraction from neem seeds (Azadirachta indica A. Juss. Family Meliaceae),
      responsible for the above activity in adult female Wistar rats. Initial studies
      with the mechanically extracted oil and solvent extracts of neem seeds have
      revealed that the antifertility activity was present in constituents of low to
      intermediate polarity. A hexane extract of neem seeds was reported to be
      biologically active (Garg et al., 1994. Comparison of extraction procedures on
      the immunocontraceptive activity of neem seed extracts. Journal of
      Ethnopharmacology 22, 87-92). Subsequently, hexane extract was sequentially
      fractionated through the last active fraction using various separation techniques
      and tested for antifertility activity at each step. Preparative HPLC was used for
      isolating individual components of the active fraction in quantities, sufficient
      for characterization. An analytical HPLC method was developed for standardization
      of the fraction. The active fraction was identified to be a mixture of six
      components, which comprises of saturated, mono and di-unsaturated free fatty
      acids and their methyl esters. Dose response study was performed with the last
      active fractions. The antifertility activity with the active fraction was
      reversible in nature and it was completely active until 5% concentration. There
      was no systemic toxic effect following the administration of the active fraction.
      This study, for the first time, proposes an active fraction from neem seeds,
      responsible for long term and reversible blocking of fertility after a single
      intrauterine administration with high efficacy.

PMID- 9613838
TI  - Ethnomedical information and in vitro screening for angiotensin-converting enzyme
      inhibition of plants utilized as traditional medicines in Gujarat, Rajasthan and
      Kerala (India).
AB  - Plants utilized as traditional medicines in India have been investigated for
      their ability to inhibit the angiotensin converting enzyme (ACE). In total, 75
      species belonging to 42 families have been investigated and new ethnomedical
      information has been obtained for 41 species. Four species were found to possess
      a high ACE inhibiting ability and were low in their tannin content.

PMID- 9613839
TI  - Antimicrobial activity of 20 plants used in folkloric medicine in the Palestinian
      area.
AB  - Ethanolic and aqueous extracts of 20 Palestinian plant species used in folk
      medicine were investigated for their antimicrobial activities against five
      bacterial species (Staphylococcus aureus, Escherichia coli, Klebsiella
      pneumoniae, Proteus vulgaris, Pseudomonas aeruginosa) and one yeast (Candida
      albicans). The plants showed 90% of antimicrobial activity, with significant
      difference in activity between the different plants. The most antimicrobially
      active plants were Phagnalon rupestre and Micromeria nervosa, whereas, the least
      active plant was Ziziphus spina-christi. Only ten of the tested plant extracts
      were active against C. albicans, with the most active from M. nervosa and Inula
      viscosa and the least active from Ruscus aculeatus. Of all extracts the ethanolic
      extract of M. nervosa was the most active, whereas, the aqueous extract of
      Phagnalon rupestre was the most active of all aqueous extracts tested. The
      ethanolic extracts (70%) showed activity against both Gram positive and negative
      bacteria and 40% of these extracts showed anticandidal activity, whereas, 50% of
      the aqueous extracts showed antibacterial activity and 20% of these extracts
      showed anticandidal activity.

PMID- 9613840
TI  - Which effective property of amino acids is best preserved by the genetic code?
AB  - Simple procedures are proposed to quantify how much an effective property
      embodied in a given ranking of the twenty amino acids can be affected by random
      point mutations at nucleotide bases. As expected, of the various orderings
      tested, rankings based on most hydrophobicity scales exhibit low scores, thus
      offering better immunity towards such single-base mutations. This, however,
      occurs to different extents and the method allows sharp discriminations between
      the scales. Hydrophobicity scales based on global properties such as spatial
      environment data of proteins residues, or mutation matrices of amino acid
      replacements, generally behave better than those based on pure physicochemical
      properties of isolated residues. An averaged scale built from the available
      hydrophobicity scales exhibits one of the most favorable scores. A systematic
      search for the best amino acid order has been carried out across all possible
      scales. Optimized scales are characterized by the existence of a clustering
      scheme into three zones, within which permutations are more or less tolerated,
      depending on the zone and on the summation procedure used in the score
      calculation. The first cluster corresponds to the hydrophobic side, and includes
      the ten amino acids WMCFILVGRS. Next follows the ATP triad. The third cluster
      coincides with the hydrophilic side and includes, in the last seven positions,
      the amino acids EDKNQHY. Interpretation of these optimized scales in terms of
      codon positions in the genetic code further suggests a clustering scheme composed
      of four groups, WMCFILV-GRS-ATP-EDKNQHY, emphasizing the role of the second base
      as the main driving parameter. As a consequence, the conserved character of the
      genetic code is better reflected when it is displayed in UGCA ordering rather
      than in the commonly used UCAG ordering. The present a priori classification of
      the amino acids could find potential use in protein sequence homology and
      structure prediction.

PMID- 9613841
TI  - The separate effects of E60Q in Lactobacillus casei thymidylate synthase
      delineate between mechanisms for formation of intermediates in catalysis.
AB  - X-Ray crystal structures of Lactobacillus casei thymidylate synthase (TS) mutant
      complexes of E60D with dUMP, and E60Q with dUMP or FdUMP, as well as ternary
      complexes with folate analog inhibitor CB3717, are described. The structures we
      report address the decrease in rate of formation of ternary complexes in the E60
      mutants. Structures of ternary complexes of L.casei TS mimic ligand-bound TS just
      prior to covalent bond formation between ligands and protein. Ternary complex
      structures of L.casei TS E60Q show the ligands are not optimally aligned for
      making the necessary covalent bonds. Since CB3717 is an analog of the open,
      activated form of the cofactor, these structures suggest that the slow rate of
      ternary complex formation in E60 mutants is at least partly the result of
      impaired alignment of ligands in the active site after binding and activation of
      the cofactor. Binary complexes of TS E60Q and TS E60D with substrate (dUMP) show
      no change in dUMP position or occupancy. These results are consistent with the
      fact that Kd(dUMP) and Km(dUMP) are almost the same, and the rates of folate
      independent debromination of 5-bromo-dUMP are even higher than for wild type TS.

PMID- 9613842
TI  - Homology model of the quinohaemoprotein alcohol dehydrogenase from Comamonas
      testosteroni.
AB  - A molecular model of QH-ADH, the quinohaemoprotein alcohol dehydrogenase from
      Comamonas testosteroni, has been built by homology modelling. Sequence similarity
      of N-terminal residues 1-570 with the alpha-subunit of quinoprotein methanol
      dehydrogenases (MDHs) from Methylophilus methylotrophus W3A1 and Methylobacterium
      extorquens provided a basis for the design of the PQQ-binding domain of QH-ADH.
      Minimal sequence similarity with cytochrome c551 from Ectothiorhodospira
      halophila and cytochrome c5 from Azotobacter vinelandii has been used to model
      the C-terminal haem c-binding domain, residues 571-677, absent in MDHs. Distance
      constraints inferred from 19F-NMR relaxation studies of
      trifluoromethylphenylhydrazine-derivatized PQQ bound to QH-ADH apoenzyme as well
      as theoretical relations for optimal electron transfer have been employed to
      position the haem- and PQQ-binding domains relative to each other. The homology
      model obtained shows overall topological similarity with the crystal structure of
      cd1-nitrite reductase from Thiosphera pantotropha. The proposed model accounts
      for the following: (i) the site that is sensitive to in vivo proteolytic attack;
      (ii) the substrate specificity in comparison with MDHs; (iii) changes of the
      spectral properties of the haem c upon reconstitution of apo-enzyme with PQQ;
      (iv) electronic interaction between haem and PQQ; and (v) enantioselectivity in
      the conversion of a chiral sec alcohol.

PMID- 9613843
TI  - Site-directed mutagenesis in hemoglobin: attempts to control the oxygen affinity
      with cooperativity preserved.
AB  - We synthesized three artificial human hemoglobin mutants in which Lys-66(E10)beta
      was replaced by Ser, Arg or Thr by site-directed mutagenic protein engineering.
      These engineered hemoglobins were designated as eHb K66betaS, eHb K66betaR and
      eHb K66betaT, respectively. By synthesizing these mutants we attempted to control
      the oxygen affinity of hemoglobin with cooperativity preserved and to clarify the
      functional role of Lys-66(E10)beta, as well. Such attempts may be useful for
      creating an oxygen carrier suitable as a blood substitute. The oxygen affinities
      of eHbs K66betaS, K66betaR and K66betaT were 1.3-, 1.5- and 2.3-fold,
      respectively, lower than that of reconstituted Hb A. Their allosteric properties
      such as the Bohr effect and the effect of inositol hexaphosphate were well
      preserved. Since the oxygen affinity of eHb K66betaT is comparable with that of
      red cells, it may be a potential candidate for a blood substitute. X-Ray
      crystallographic data for Hb Chico [Lys-66beta-->Thr], which is identical with
      eHb K66betaT, together with our computer simulation indicate that an interaction
      between the introduced Thr and the distal His via a water molecule lowers the
      oxygen affinity for the T state eHb K66betaT.

PMID- 9613844
TI  - Synthesis and characterization of a stable analog of the phosphorylated form of
      the chemotaxis protein CheY.
AB  - The bacterial chemotaxis protein CheY is activated in vivo by the covalent
      phosphorylation of a single aspartate residue at position 57. However, this
      phosphate linkage is unstable (t1/2 approximately 20 s at room temperature),
      thereby precluding many biochemical analyses. Here we present a synthetic scheme
      to prepare an analog of CheY-phosphate (Che Y-P) with chemical stability of the
      phosphate linkage enhanced by several orders of magnitude relative to the native
      protein. Starting with CheY D57C, a site-specific mutant of CheY with a unique
      cysteine residue in place of the aspartate at position 57, two sequential
      disulfide exchange reactions were performed to form the final product 'CheY D57C
      SPO3' with a thiophosphate moiety covalently bonded to the protein in a disulfide
      linkage. Mass spectral analysis showed that the desired analog was present at 70
      80% of the total protein. The disulfide linkage had a t1/2 of 8 days at 4 degrees
      C. Biochemical characterization of CheY D57C-SPO3 included assessment of
      conformational properties using tryptophan fluorescence, evaluation of metal
      binding properties and measurement of binding interactions with the chemotaxis
      proteins CheZ and FliM. Despite possessing a phosphoryl group at a nearly
      identical location as native CheY-phosphate, the analog was unable to emulate
      CheY-phosphate function, thereby supporting the idea that there are very precise
      geometric requirements for successful CheY activation.

PMID- 9613845
TI  - Incorporation of 1,2,4-triazole-3-alanine into a mutant of phage lambda lysozyme
      containing a single histidine.
AB  - The only histidine residue in the H31N-H137N double mutant of phage lambda
      lysozyme (lambdaL), at position 48, was biosynthetically replaced by the analogue
      1,2,4-triazole-3-alanine (Taz), the basicity of which is 3 pKa units lower. A
      histidine-auxotrophic strain was grown to stationary phase by histidine
      limitation in a synthetic medium, then Taz was added on induction to produce a
      lysozyme with approximately 75% incorporation. The Taz-containing enzyme
      precipitated selectively from the cytoplasm and was purified after renaturation.
      Replacement by Taz had only very minor effects on the activity-pH profile of the
      enzyme, in contrast with the great perturbations observed for the Asn48 mutant.
      The relative stabilities of the His48-lambdaL and Taz48-lambdaL mutants were also
      studied as a function of pH; the results are discussed with regard to the poor
      accessibility of His48, the low basicity of Taz and the hydrogen bonding patterns
      suggested by the crystal structure. At neutral pH, Taz48-lambdaL is less stable
      than His48-lambdaL by approximately 3.5 kcal/mol, probably as a result of the
      loss of a hydrogen bond in the native form of Taz48-lambdaL. Lowering the pH
      leads to a progressive stabilization of Taz48-lambdaL relative to His48-lambdaL
      because of the abnormally low pKa of His48 in the native form of His48-lambdaL.

PMID- 9613846
TI  - Chimeric small subunit inhibitors of mammalian ribonucleotide reductase: a dual
      function for the R2 C-terminus?
AB  - Here we report on the formation and activity of complexes between the large
      subunit (mR1) dimer of mouse ribonucleotide reductase (mRR) and small subunit
      chimeric dimers (cR2) derived from Escherichia coli and mouse small subunits. cR2
      subunits were constructed by substituting mouse C-terminal gene sequences, coding
      for either 7 or 33 amino acid residues, for the corresponding E.coli R2 (eR2)
      sequences, with the remainder of the gene corresponding to eR2. The purified cR2s
      contained the micro-oxo bridged diferric center and tyrosine radical necessary
      for reductase activity, although the radical signal was broadened compared with
      wild-type eR2. Neither chimera formed an active complex with mR1, but each was a
      competitive inhibitor, with respect to mR2, of mRR activity. The inhibition
      constants for both chimeras were similar, and were sevenfold higher than the
      dissociation constant of mR2 dimer to mR1 dimer (0.24 +/- 0.02 microM). Analysis
      of inhibition data showed that chimeric R2 subunits bind to mammalian R1 with a
      1:1 (R1:R2) stoichiometry and permit the inference that both C-termini in a cR2
      dimer bind to the two sites per mR1 dimer. The lack of enzymatic activity in the
      mR1-cR2 complex is attributed to perturbation or elimination of interactions
      linking the tyrosine radical/dinuclear iron center and the C-terminus within R2.

PMID- 9613847
TI  - High affinity IgG binding by FcgammaRI (CD64) is modulated by two distinct IgSF
      domains and the transmembrane domain of the receptor.
AB  - The high affinity IgG receptor, FcgammaRI, is comprised of three immunoglobulin
      superfamily (IgSF) domains (EC1, EC2 and EC3), a single transmembrane spanning
      region, and a short cytoplasmic tail. We have shown a role for three separate
      domains of FcgammaRI in the high affinity binding of IgG. Affinity measurements
      of chimeric FcgammaRs in which EC1 and EC2 of FcgammaRI have been replaced with
      the homologous EC1 and/or EC2 domains of the low affinity IgG receptor,
      FcgammaRII indicate that both EC2 and EC3 are essential for high affinity binding
      of monomeric IgG. Identification of EC3 from FcgammaRI as the binding site for
      the monoclonal antibody 10.1, which blocks IgG binding, provides further evidence
      for the role of this domain in binding. In addition, we have found that the
      affinity of FcgammaRI is increased threefold when co-expressed with its accessory
      molecule, gamma-chain. Affinity measurements of further chimeras indicates that
      the transmembrane domain of FcgammaRI has a negative influence upon the affinity
      of the receptor. To account for these observations, we propose that receptor
      dimerization is required for maximal affinity of FcgammaRI. Dimerization may
      serve as the mechanism by which IgG binding triggers several FcgammaRI-mediated
      events.

PMID- 9613848
TI  - Construction of mono- and bivalent human single-chain Fv fragments against the D
      antigen in the Rh blood group: multimerization effect on cell agglutination and
      application to blood typing.
AB  - An expression system for mono- and bivalent single-chain Fv fragments (scFv) of a
      human antibody against D antigen in the Rh blood group system was established in
      Escherichia coli. The cDNA encoding the Fv fragment of the anti-D monoclonal
      antibody D10 was cloned using the polymerase chain reaction and expressed in
      E.coli by fusing with a peptide tag link in the C-terminus of the light chain
      variable region. The scFv fragment expressed by the bacteria produced specific
      agglutination of human D positive red cells in the presence of an anti-peptide
      tag antibody. Flow cytometric analysis clearly indicated that the bacterially
      prepared scFv showed high specificity and affinity for D antigen, which was
      identical with that of the parental IgG. In order to construct bivalent D10 scFv
      for use in direct cell agglutination, the scFv was fused with a dimeric protein,
      bacterial alkaline phosphatase (BAP). The fusion protein produced significant
      agglutination of human red blood cells with D antigen, confirming that the
      bacterially expressed fusion protein is a functional bivalent antibody fragment.
      Specific agglutination of D positive red cells by D10 scFv-BAP was enhanced in
      the presence of anti-BAP antibody, suggesting that further multimerization of
      scFv led to highly efficient cell agglutination. By grafting BAP enzymatic
      activity into the scFv fragment (enzyme-linked scFv), blood typing could
      conveniently be performed. These results indicate that bacterially expressed scFv
      and scFv-BAP would be of practical use in blood typing. The system reported here
      could also be applied to the examination of other cell surface antigens and cell
      agglutination.

PMID- 9613849
TI  - Isolation of anti-glutathione antibodies from a phage display library.
AB  - We have isolated anti-glutathione antibodies from a human synthetic phage
      antibody scFv library (Nissim,A., Hoogenboom,H.R., Tomlinson,I.M., Flynn,G.,
      Midgley,C., Lane,D. and Winter,G., 1994, EMBO J., 13, 692-698). Glutathione (GSH)
      conjugates with carrier proteins, such as bovine serum albumin (BSA), keyhole
      limpet hemocyanin (KLH) and human lysozyme (LZM), were used as antigens. After
      four cycles of panning and affinity chromatography, clones that recognized GSH
      conjugated proteins, but not BSA, KLH or LZM, were isolated. The isolated phage
      antibodies and the soluble scFv fragments were characterized by immunoblotting,
      and the nucleotide sequences of the VH segments of selected clones were
      determined. The binding of several isolates to GSH-BSA was competitively
      inhibited by GSH in an ELISA. These observations have demonstrated that
      antibodies against GSH, a tripeptide, can be isolated from the library. We
      constructed the tertiary models of several scFv fragments and discussed the
      mechanism of antigen binding sites.

PMID- 9613850
TI  - Tyrosine hydroxylase gene associated with depressive symptomatology in mood
      disorder.
AB  - Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the synthesis of
      dopamine and norepinephrine. It may be involved in the pathophysiology of
      psychiatric disorders and positive associations have been reported for TH gene
      markers in mood disorders. While most replications failed to confirm the initial
      findings, other papers suggested a potential role of this gene in the etiology of
      mood disorders. Among the many different reasons for a lack of consistent
      replications, a critical role is played by the "correct" phenotype
      identification. Actually, up to now the only classification criteria has been the
      psychiatric diagnosis, but within the same psychiatric diagnoses the
      symptomatologic presentation may vary dramatically depending upon severity,
      presence of psychotic features or other psychopathologic traits. Thus, the aim of
      our study is to evaluate a possible association for TH gene with symptomatology
      in a sample of subjects affected by mood disorders. We have developed a phenotype
      definition based on the observed symptomatology divided into the four factors
      "Excitement," "Depression," "Delusion," and "Disorganization." Our sample
      includes 46 mood disorder subjects, investigated by the OPCRIT (operational
      criteria checklist for psychotic illness) checklist for their symptomatological
      pattern and typed for TH variants by polymerase chain reaction (PCR)
      amplification. Depressive factor was associated with TH variants (F = 4.79, df =
      4, 87, P = 0.006), with TH*2 subjects presenting lower depressive scores.
      Subjects with genotype TH*2/2 were the only ones in the sample to report mild
      depressive episodes. TH variants may be related with depressive symptomatology in
      subjects affected by mood disorders.

PMID- 9613851
TI  - Association study of structural mutations of the tyrosine hydroxylase gene with
      schizophrenia and Parkinson's disease.
AB  - Tyrosine hydroxylase (TH) gene is the rate-limiting enzyme in the synthesis of
      catecholamines. Functional polymorphisms of the TH gene may be involved in the
      pathogenesis of neuropsychiatric diseases such as schizophrenia, affective
      disorders, and Parkinsonism. This study examined a possible association of two
      polymorphisms, both of which result in an amino acid change of the TH protein,
      with schizophrenia and Parkinson's disease (PD). The Val81Met polymorphism is a
      common variation, although its effect on the enzyme expression is unclear.
      Leu205Pro polymorphism is a rare mutation that is reported to cause Parkinsonism
      in infancy for individuals who are homozygous for the mutated type. We genotyped
      a Japanese sample of 194 schizophrenics, 99 patients with PD, and 161 controls
      for the Val81Met polymorphism by using mis-match PCR and digestion by the
      restriction enzyme BalI. There was no significant allelic or genotypic
      association of the Val81Met polymorphism with schizophrenia or PD. The Leu205Pro
      polymorphism was examined by using PCR and digestion by AluI; however, there was
      no individual who carried the mutated type of Pro205 among 50 schizophrenics or
      50 patients with PD. Thus we obtained no evidence for the involvement of the two
      structural mutations of the TH gene in the pathogenesis of schizophrenia or PD.

PMID- 9613852
TI  - Analysis of SCA1, DRPLA, MJD, SCA2, and SCA6 CAG repeats in 48 Portuguese ataxia
      families.
AB  - The spinocerebellar ataxias (SCAs) are clinically and genetically a heterogeneous
      group of neurodegenerative disorders. To date, eight different loci causing SCA
      have been identified: SCA1, SCA2, Machado-Joseph disease (MJD)/SCA3, SCA4, SCA5,
      SCA6, SCA7, and dentatorubropallidoluysian atrophy (DRPLA). Expansion of a CAG
      repeat in the disease genes has been found in five of these disorders. To
      estimate the relative frequencies of the SCA1, DRPLA, MJD, SCA2, and SCA6
      mutations among Portuguese ataxia patients, we collected DNA samples from 48
      ataxia families and performed polymerase chain reaction (PCR) amplification of
      the CAG repeat mutations on chromosomes 6p, 12p, 14q, 12q, and 19p, respectively.
      Fifty-five individuals belonging to 34 dominant families (74%) had an expanded
      CAG repeat at the MJD gene. In five individuals from two kindreds with a dominant
      pattern of inheritance (4%), an expanded CAG repeat at the SCA2 gene was found.
      In MJD patients, the normal allele size ranged from 13 to 41, whereas the mutant
      alleles contained 65 to 80 repeats. For the SCA2 patients, normal alleles had 22
      or 23, while expanded alleles had between 36 and 47 CAG units. We did not find
      the SCA1, DRPLA, or SCA6 mutations in our group of families. The MJD mutation
      remains the most common cause of SCA in Portugal, while a small number of cases
      are caused by mutations at the SCA2 gene, and 22% are due to still unidentified
      genes.

PMID- 9613853
TI  - Results of a genome-wide genetic screen for panic disorder.
AB  - Panic disorder is characterized by spontaneous and recurrent panic attacks, often
      accompanied by agoraphobia. The results of family, twin, and segregation studies
      suggest a genetic role in the etiology of the illness. We have genotyped up to 23
      families that have a high density of panic disorder with 540 microsatellite DNA
      markers in a first-pass genomic screen. The thirteen best families (ELOD > 6.0
      under the dominant genetic model) have been genotyped with an ordered set of
      markers encompassing all the autosomes, at an average marker density of 11 cM.
      Over 110,000 genotypes have been generated on the whole set of families, and the
      data have been analyzed under both a dominant and a recessive model, and with the
      program SIBPAIR. No lod scores exceed 2.0 for either parametric model. Two
      markers give lod scores over 1.0 under the dominant model (chromosomes 1p and
      20p), and four do under the recessive model (7p, 17p, 20q, and X/Y). One of these
      (20p) may be particularly promising. Analysis with SIBPAIR yielded P values
      equivalent to a lod score of 1.0 or greater (i.e., P < .016, one-sided,
      uncorrected for multiple tests) for 11 marker loci (2, 7p, 8p, 8q, 9p, 11q, 12q,
      16p, 20p and 20q).

PMID- 9613854
TI  - Study of behavioral phenotypes: goals and methodological considerations.
AB  - The study of behavioral phenotypes associated with genetic syndromes has gained
      increasing momentum over the past two decades. In this paper, the definition of
      behavioral phenotypes is presented and the complexities and obstacles to progress
      in this field are summarized. Also described are the goals of such
      investigations, including the need for syndrome delineation, provision of
      guidance for clinical management, contributions to understanding brain-behavior
      relations, advancements in developmental theory, and gaining understanding of the
      genetic bases of behavior. Methodological issues addressed in relation to such
      goals include the need for cross-disciplinary collaboration, concerns regarding
      sampling methods and comparison group selection, and developmental
      considerations. The complexity of cognitive abilities, the limitations of
      existing tests and measures, and ways of approaching the study of behavior are
      discussed. A final comment concerns the potential risks of research in behavioral
      phenotypes.

PMID- 9613855
TI  - Paternal transmission and anticipation in schizophrenia.
AB  - Recent studies have observed anticipation (earlier age at onset (AAO) or
      increased disease severity in successive generations) in familial schizophrenia.
      In other disorders, where the molecular mechanism (repeat expansion) is known,
      anticipation varies in degree depending on the sex of the transmitting parent. We
      investigated parental sex effects on anticipation in schizophrenia, using a
      familial sample of affected two-generation pairs in which anticipation had
      previously been demonstrated using the median intergenerational difference (MID)
      in AAO. A Wilcoxon rank sum test for independent samples was used to determine
      whether MID in AAO was significantly different for paternal and maternal
      transmission. Results suggested that in a sample of 127 parent-offspring pairs,
      anticipation was greater with paternal than with maternal transmission (MID = 18
      and 14 years, respectively, P = 0.05). Paternal effects were strongest in 39
      parent-offspring pairs with early-onset offspring (< or = 21 years) (MID = 22 and
      17 years, respectively, for paternal and maternal transmission, P = 0.01).
      However, assessment of the effect of possible selection biases suggests that
      preferential ascertainment of late-onset fathers may have exerted important
      effects. While the results support possible paternal effects, further studies are
      needed to draw firm conclusions about true parent-of-origin effects on
      anticipation in familial schizophrenia.

PMID- 9613856
TI  - Lack of association between dopamine transporter gene polymorphisms and
      delusional disorder.
AB  - Potential contributions of dopamine transporter (DAT) gene variants to delusional
      disorder were investigated using association analysis. DAT gene VNTR
      polymorphisms were assessed in 61 delusional patients and 54 normal controls. No
      differences were found in either genotypic or allelic distributions. These
      findings do not support relevant contributions of DAT gene variants to the
      pathogenesis of delusional disorder.

PMID- 9613857
TI  - Exclusion of genetic linkage to 4q21-23 and 17q21 in a family with Lewy body
      parkinsonism.
AB  - Genetic analysis of markers from chromosomes 4q21-23 and 17q21 in a family with
      apparently autosomal dominant Lewy body parkinsonism is presented. This analysis
      shows that the locus leading to this disease is not allelic with that previously
      shown to lead to Lewy body parkinsonism on chromosome 4 or to the locus on
      chromosome 17 leading to frontotemporal dementia with parkinsonism. A brief
      clinical comparison of this family with families showing linkage to these loci is
      presented. The data suggest that at least one other major genetic determinant for
      Lewy body parkinsonism remains to be identified.

PMID- 9613859
TI  - Behavioral phenotype of Smith-Magenis syndrome (del 17p11.2).
AB  - Smith-Magenis syndrome (SMS) is a distinct and clinically recognizable multiple
      congenital anomaly (MCA) and mental retardation syndrome caused by an
      interstitial deletion of chromosome 17 p11.2. The phenotype of SMS has been well
      described and includes: a characteristic pattern of physical features; a hoarse,
      deep voice; speech delay with or without associated hearing loss; signs of
      peripheral neuropathy; variable levels of mental retardation; and neurobehavioral
      problems. Although self-injury and sleep disturbance are major problems in SMS,
      studies are limited on the behavioral phenotype of SMS. This report reviews the
      current state of knowledge about SMS and presents new data based on syndrome
      specific observations by the authors' longitudinal experience working with SMS,
      specifically related to the behavioral aspects of SMS. This information should
      have relevance for parents, clinicians, geneticists, and educators involved in
      the care of individuals with SMS.

PMID- 9613858
TI  - Scanning of the dopamine D1 and D5 receptor genes by REF in neuropsychiatric
      patients reveals a novel missense change at a highly conserved amino acid.
AB  - In previous analyses of schizophrenic patients, multiple missense changes and one
      nonsense change were identified in the D5 dopamine receptor (DRD5) gene, but no
      sequence changes of likely functional significance were identified in the D1
      dopamine receptor (DRD1) gene. In the present study, we examined these genes in
      patients with certain other neuropsychiatric disorders that may be related to
      dopaminergic dysregulation. The coding regions of the DRD1 and DRD5 genes were
      examined in 25 and 25 autistic patients, 25 and 28 attention deficit
      hyperactivity disorder patients, and 51 and 43 alcoholic patients, respectively.
      In addition, the DRD5 gene was examined in 75 schizophrenic patients to search
      for additional variants affecting protein structure or expression (VAPSEs). These
      patients were analyzed with REF (restriction endonuclease fingerprinting), a
      hybrid between SSCP and restriction endonuclease digestion, which allows the
      entire coding sequence to be screened in one lane of a gel. Approximately 800 kb
      of genomic sequence were examined. No sequence changes were identified in the
      DRD1 gene among the 101 patient samples analyzed. Two sequence changes were
      identified in the DRD5 gene among the 171 patient samples. These included one
      previously identified silent polymorphism at base pair 978 (P326P). The change
      was identified in patients from all disease categories and from different ethnic
      backgrounds. One novel missense change, L88F, occurred in transmembrane domain II
      at a highly conserved amino acid in all dopamine receptors as well as in alpha1-
      and beta-adrenergic receptors. The mutation was identified in a Caucasian male
      patient with autism. Further analysis is necessary to determine if this missense
      change is associated with a particular neuropsychiatric phenotype.

PMID- 9613860
TI  - Sleep disturbance in Smith-Magenis syndrome (del 17 p11.2).
AB  - Smith-Magenis syndrome (SMS) is a clinically recognizable multiple congenital
      anomaly and mental retardation syndrome caused by an interstitial deletion of
      chromosome 17 p11.2. Although the physical and molecular genetic features of SMS
      are increasingly well understood, work is more limited on SMS's behavioral
      phenotype, which includes self-injury, tantrums, and sleep disturbance. This
      study examines the sleep behaviors of 39 individuals with SMS, ranging in age
      from 1.6 to 32 years (mean = 10.5). Prominent sleep problems, seen in 65 to 100%
      of the sample, included difficulties falling asleep, shortened sleep cycles,
      frequent and prolonged nocturnal awakenings, excessive daytime sleepiness,
      daytime napping, snoring, and bed-wetting. Medication to facilitate sleep was
      used by 59% of SMS subjects. Possible etiologic mechanisms of sleep disturbance
      in SMS are discussed, as are recommended interventions.

PMID- 9613861
TI  - Association between novelty-seeking and the dopamine D3 receptor gene in bipolar
      patients: a preliminary report.
AB  - Recent studies in healthy controls suggest an association between novelty-seeking
      (NS) and the dopamine D4 receptor (DRD4) gene. In this study, we further
      investigated the relationship between genes implicated in dopamine as well as
      serotonin neurotransmission and personality traits in bipolar (BP) disorder.
      Scores on the Tridimensional Personality Questionnaire were examined in 37
      recovered Research Diagnostic Criteria-diagnosed BP patients genotyped for DRD3,
      DRD4, and serotonin 2A receptor (5HTR2a) polymorphisms. Carriers of DRD3 allele 1
      showed significantly lower NS values compared to patients without this allele.
      Scores on NS and on harm-avoidance were not related to DRD4 or 5HTR2a
      polymorphisms. These preliminary results suggest a role for D3 receptor in NS
      expression in BP patients.

PMID- 9613862
TI  - About the use of APOE in Alzheimer's disease studies.

PMID- 9613863
TI  - Initial results of a genome survey for novel Alzheimer's disease risk genes:
      association with a locus on the X chromosome.
AB  - As the initial step in a systematic genome survey, 16 simple sequence tandem
      repeat polymorphisms that span the X chromosome at an average spacing of 10 cM
      were examined for allelic associations with typical-onset Alzheimer's disease
      (AD). The efficiency of this survey was substantially enhanced by genotyping
      pools of genomic DNA from 50 autopsy-confirmed AD cases and 50 autopsied controls
      who were similar in sex ratio, race, and age at death. The frequency of the
      DXS1047 202-bp allele was twice as common among AD cases (0.45 +/- S.E. 0.06)
      than controls (0.22 +/- S.E. 0.05), a finding that was reproduced in an
      independent and geographically disparate sample. Consistent with Hardy-Weinberg
      equilibrium, the proportion of women with AD who carried the 202-bp allele, 73%
      was nearly double that observed for men with AD, 38%. However, the frequency of
      the 202-bp allele was similar for men and women and the presence of this allele
      did not affect the age at onset of dementia in either sex. Furthermore, the
      frequency of the DXS1047 202-bp allele in AD cases and controls was unaffected by
      the APOE genotype, indicating that these two loci modulate AD risk independently.
      Finally, the frequency of the 202-bp allele among 50 autopsy-confirmed cases of
      Parkinson's disease (0.29 +/- S.E. 0.06) was indistinguishable from the control
      value, reflecting relative specificity for this allelic association with AD.

PMID- 9613864
TI  - Cell and molecular biology of kidney development.
AB  - Studies that address the cellular and molecular biology of renal organogenesis
      are relevant to our understanding of normal renal developmental mechanisms,
      developmental renal diseases, and the kidney's response to injury. Responses of
      the mature kidney to many injuries often involve cellular and molecular
      reparative processes that mimic development. This article will focus on recent
      data concerning regulators of renal differentiation; the roles of cell growth
      regulation, apoptosis, and intracellular signaling in kidney development; and
      specific mechanisms of renal epithelial, vascular, and interstitial development.
      Understanding the basic processes that occur in renal organogenesis provides
      insight into possible pathophysiological mechanisms operative in a wide range of
      renal diseases.

PMID- 9613865
TI  - The genetic basis of pediatric renal disease.
AB  - The goals of this brief review are to provide current information on the
      pathogenesis of important genetic renal diseases that present in childhood and to
      discuss the impact of these fresh insights on the diagnosis of these conditions.
      Space limitations preclude detailed consideration of each disorder.

PMID- 9613866
TI  - Immunization guidelines for pediatric renal disease.
AB  - It is imperative that pediatric nephrologists monitor the immunization status of
      pediatric chronic renal insufficiency, dialysis and transplantation patients
      closely to reduce the risk of vaccine-preventable disease. Pediatric patients
      with chronic renal insufficiency and those on dialysis should receive all the
      standard immunizations according to the schedule as deliniated by the Red Book.
      In addition to these standard vaccines, these patients will also benefit from
      influenza and pneumococcal vaccine. Pediatric renal transplant recipients should
      also be immunized with standard and special vaccines; however, all live viral
      vaccines should be avoided in this population. Because patients with renal
      disease may not respond optimally to all immunizations, it is important to study
      antibody response to MMR and varicella in patients before transplantation. If
      these patients are unprotected, they should be immunized before transplantation.
      It seems that pediatric dialysis and transplantation patients may not respond
      optimally to hepatitis B vaccine. Therefore, if at all possible, this vaccine
      should be administered before these therapies. Doubling the recommended dose of
      hepatitis B vaccine may improve response. Antibody levels to hepatitis B should
      be monitored every other year, and this vaccine should be readministered when the
      antibody level decreases to less than 10 mIU/mL. Hopefully the morbidity and
      mortality associated with vaccine-preventable disease can be reduced in this
      population by ensuring that pediatric patients with chronic renal disease are
      adequately immunized.

PMID- 9613867
TI  - Update on childhood urinary tract infections and reflux.
AB  - Urinary tract infections (UTIs) are a common and potentially serious source of
      morbidity in infants and children. In the absence of identifiable structural
      and/or functional abnormality of the urinary tract that would predispose to UTI,
      such as vesicoureteric reflux (VUR), significant and permanent injury to the
      renal parenchyma (pyelonephritic scarring) from UTI is uncommon. However, those
      patients with such predisposing conditions are at risk for adverse long-term
      outcomes of pyelonephritic scarring such as hypertension and/or impairment of
      glomerular filtration rate (GFR). Although the acute symptomatology usually
      responds promptly to proper antibiotic therapy, the treating physician must be
      concerned with a number of intermediate and long-term health outcomes.
      Specifically, is bacteriuria associated with renal parenchymal inflammation? If
      so, will it heal with restoration of normal architecture (and function), or will
      there be replacement of formerly healthy renal tissue with fibrosis? How can
      future UTIs, each with their attendant risk of pyelonephritic scarring, be
      prevented? What combination of initial diagnostic tests and follow-up management
      are best suited for which patients to minimize such adverse outcomes? The
      approach to the diagnostic evaluation for structural and functional disturbances
      in the urinary tract that would predispose to UTI has evolved to answer these
      questions. This review will focus on the recent advances in the detection and
      management of uropathology associated with UTI, particularly that of
      vesicoureteral reflux (VUR).

PMID- 9613868
TI  - Renal manifestations of systemic diseases.
AB  - During childhood, the kidney may be involved in several different systemic
      diseases including the vasculitic syndromes, collagen vascular diseases, and the
      thrombotic microangiopathic diseases. This article discusses three of the more
      common systemic disease including Henoch Schonlein Purpura (HSP), systemic lupus
      erythematosus (SLE), and the hemolytic uremic syndrome (HUS), which occur during
      childhood. Each of these diseases have important renal manifestations that may
      present with hematuria with or without proteinuria, hypertension, rapidly
      progressive glomerulonephritis, and/or with acute renal failure. The occurrence
      of these diseases during childhood raises lifelong concerns for the child's renal
      function. As in glomerulonephritis associated with SLE, reactivation of the
      underlying disease can result in additional renal injury, whereas late extrarenal
      and renal complications may be observed following HUS or nephritis associated
      with HSP. These diseases are not only an important cause of acquired chronic
      renal failure during childhood, but may also lead to end-stage renal disease or
      other complications that do not become apparent until adulthood. In each disease,
      we will review the clinical manifestations, the pathology, pathophysiology, and
      current management and therapy.

PMID- 9613869
TI  - The mineral disorders in pediatrics.
AB  - There is increasing awareness of the role that metals/minerals play in health and
      disease. Minerals contribute in essential ways to the fundamental biochemical and
      physiological functions of cells. Deficit of an essential mineral leads to
      aberrations in cell function. Alternatively, minerals in excess have significant
      toxicity, and in an era of increasing threat to a safe environment, the potential
      for toxic tissue injury to contribute to progressive renal insufficiency and
      ultimately to unexplained renal failure remains a major concern. This review
      provides information on selected minerals that are attracting growing attention
      with respect to their influence on renal function in health and disease. Although
      all minerals have the potential to cause toxicity if consumed in sufficient
      quantity, most are essential nutrients whose deficiency is associated with
      significant health problems. Certain minerals, including aluminum, arsenic,
      cadmium, lead, and mercury are considered toxic. Their suggested positive effects
      on the health of animals has been recently summarized, but in humans they are not
      currently known to exert any clearly beneficial biological or biochemical effect.

PMID- 9613870
TI  - Special topics in pediatric hypertension.
AB  - This review emphasizes four major areas of pediatric hypertension. Because
      hypertension is the most common reason student athletes fail the sports pre
      participation examinations, we have attempted to provide a rationale approach to
      the decision process to permit a hypertensive child to partake in leisure and
      competitive sports. Without question, obesity is a major reason for referral for
      hypertension to a pediatric nephrologist. The work-up should be directed to diet
      control and an exercise program to achieve sustained weight reduction.
      Hypertension associated with chronic renal failure and renal disease secondary to
      insulin-dependent diabetes mellitus is a major problem in pediatric and adult
      nephrology. With adequate control of systemic blood pressure, progressive decline
      in renal function may be delayed. By understanding these common areas of
      associated pediatric hypertension, a more systematic approach to the evaluation
      and treatment can be achieved.

PMID- 9613871
TI  - The nephrotic syndrome: from the simple to the complex.
AB  - The nephrotic syndrome represents a series of physiological results ensuing from
      the occurrence of significant urinary loss of protein. Although the common
      initiating event of proteinuria has long been established, the list of problems
      that result has continued to grow as our understanding of the pathophysiology of
      nephrosis has increased. This article discusses this pathophysiology, emphasizing
      the consequences of nephrotic-range proteinuria. These consequences include not
      only acute and subacute manifestations of disrupted homeostasis, but also ways in
      which nephrosis itself may amplify mechanisms by which progressive renal nephron
      loss occurs. New insights into the factors that initiate and maintain
      glomerulosclerosis and interstitial fibrosis may offer potential approaches to
      preventing or ameliorating chronic renal insufficiency.

PMID- 9613872
TI  - Diagnosis and treatment of renal tubular disorders.
AB  - There is a wide variety of renal tubular disorders affecting children.
      Understanding the pathophysiology of each disease assists in the recognition and
      treatment of these diseases, which can have profound effects on a child's growth
      and development. We review some of the more common tubular disorders found in
      children, emphasizing those conditions in which recent advances have been made in
      understanding of the specific genetic or physiological defect responsible:
      Fanconi's syndrome, cystinuria, renal tubular acidosis, and the hypokalemic
      metabolic alkaloses. Current recommendations are presented for diagnosing and
      treating these conditions.

PMID- 9613873
TI  - Nephrology in the pediatric intensive care unit.
AB  - Electrolyte abnormalities, hypertension and acute renal failure commonly occur in
      children admitted to the intensive care unit. Perturbations in sodium, potassium,
      and calcium or hypertensive crisis require prompt therapy to avoid major cardiac
      or neurological events. Hemodialysis, peritoneal dialysis, or hemofiltration can
      effectively and safely be performed, even in small and hemodynamically unstable
      children. Although suitable equipment is available for all renal replacement
      options, attention to precise details such as fluid administration and flow rates
      are essential.

PMID- 9613874
TI  - Current advances in the therapy of chronic renal failure and end stage renal
      disease.
AB  - The improved outcomes recently experienced by children with chronic renal failure
      and end stage renal disease (ESRD) does not obviate the need to strive to better
      the quality of their physical, mental and emotional well-being. This article
      reviews some of the recent advances in the care of these children that are
      intended to achieve that goal. Dialysis topics include prescription, novel
      solutions, adequacy measures, management of anemia, and access. Transplantation
      areas covered include graft and patient survival, growth, organ availability,
      opportunistic infections and immunity, immunosuppressive agents, and transplant
      related malignancies. The care of the pre-ESRD patient is discussed with a review
      of new data that are being compiled in this patient population.

PMID- 9613875
TI  - An ethical dilemma in subspecialty pediatrics.

PMID- 9613876
TI  - What is the appropriate workup for a child with a multicystic dysplastic kidney?

PMID- 9613877
TI  - What is the appropriate evaluation and therapy for children with hypercalciuria
      and hematuria?

PMID- 9613878
TI  - What are normal potassium concentrations in the neonate? What is a reasonable
      approach to hyperkalemia in the newborn with normal renal function?

PMID- 9613879
TI  - What is the appropriate workup and treatment for an infant with an umbilical
      artery catheter-related thrombosis?

PMID- 9613880
TI  - What are the possible causes of neonatal nephrocalcinosis?

PMID- 9613881
TI  - Should cyclosporine replace cytoxan or chlorambucil as the second-line drug for
      steroid-dependent nephrotic syndrome?

PMID- 9613882
TI  - With the constraints of managed care, what is a reasonable workup for microscopic
      hematuria?

PMID- 9613883
TI  - Reasons for repeated medical visits among patients with chronic back pain.
AB  - OBJECTIVE: This study identifies the key motivations of patients repeatedly
      seeking medical care for chronic back problems. DESIGN: We conducted one-on-one,
      in-depth interviews with patients to discuss their experiences with low back pain
      and its care. To validate our interpretation of the qualitative data,
      participants were mailed questionnaires listing the themes identified in the
      interviews and asked to rate the importance to them of each of the themes.
      SETTING: Managed health care plans in Atlanta, Dallas, and Seattle. PARTICIPANTS:
      Fifty-four patients (37% male, 63% female) who were 25 to 65 years of age and had
      three or more medically attended episodes of low back pain during the 3 years
      preceding the study. MAIN RESULTS: In describing their motivations for seeking
      medical care for back pain, nearly all participants cited difficulty in
      performing normal activities and the desire to discover the cause of the pain.
      Other motivations for seeking medical care for back pain included increased pain
      and the desire for a diagnostic test or a new treatment. Many of the verbalized
      reasons for repeated medical visits among patients with chronic back pain are
      probably best understood as seeking validation of their suffering. CONCLUSIONS:
      Patients with chronic back pain report many unmet needs and expectations. Overall
      satisfaction might be improved if clinicians elicit patients' views of underlying
      causes and their expectations from office visits.

PMID- 9613884
TI  - Reduced labor force participation among primary care patients with headache.
AB  - OBJECTIVE: To assess the long-term impact of headache on labor force
      participation among primary care patients with headache. DESIGN: A 2-year cohort
      study comparing employment status of primary care patients with headache and that
      of patients with back pain. PARTICIPANTS: Patients with headache (n = 662) or
      back pain (n = 1,024) sampled from persons visiting a primary care physician who
      completed baseline, 1-year and 2-year follow-up interviews. MEASUREMENTS AND MAIN
      RESULTS: The percentage of subjects unemployed at baseline, 1 year or 2 years was
      determined, excluding the retired and homemakers. Among all patients, the
      percentage unable to obtain or keep full-time work in the year prior to each
      interview because of headache or back pain was also assessed. Over the 3-year
      period covered by the study interviews, 13% of headache and 18% of back pain
      patients were unable to obtain or keep full-time work because of their pain
      condition. Among those in the labor force, 12% of headache patients and 12% of
      back pain patients were unemployed for any reason at one or more interviews.
      Among the one in five headache patients with a poor long-term outcome, 36% were
      unable to obtain or keep full-time work because of headache at some time compared
      with 4% of headache patients with a good outcome. Among headache patients, women,
      persons aged 18 to 24 years, those with lower levels of education, persons with
      depressive symptoms, and migraineurs were more likely to have reduced labor force
      participation owing to headache. CONCLUSIONS: The likelihood of reduced labor
      force participation among primary care patients with headache was considerable
      and concentrated among the one in five patients with a poor long-term outcome.
      Headache patients at a social disadvantage in attaining occupational role
      stability (e.g., younger women or poorly educated patients) were more likely to
      report reduced labor force participation.

PMID- 9613885
TI  - Risk factors for self-reported colon polyps.
AB  - OBJECTIVE: Investigate risk factors for colon polyp using multivariate analyses.
      DESIGN: In a group responding to a 1992 mail survey, we assessed the association
      between physician-diagnosed colon polyp and possible risk factors reported
      primarily 10 years earlier. SETTING: Survey respondents within the Cancer
      Prevention Study II. PARTICIPANTS: Respondents, 72,868 men and 81,356 women, who
      reported no polyp diagnosis when questioned in 1982 at ages 40 to 64 years.
      MEASUREMENTS AND MAIN RESULTS: The characteristics of 7,504 men (10.3%) and 5,111
      women (6.3%) reporting a first colon polyp were compared with those of
      participants who did not report a polyp. After adjustments for age, family
      history of colorectal cancer, and other potential risk factors, polyp occurrence
      was associated with 1982 histories of smoking, former smoking, alcohol use of at
      least two drinks per day (odds ratios [ORs] from 1.5 to 1.1; all p < .005), and a
      body mass index > or = 28 kg/m2 (men's OR 1.06; 95% confidence interval [CI]
      1.00, 1.13; women's OR 1.08; 95% CI 0.99, 1.17). Polyps were also associated with
      a diagnosis of gallbladder disease or gallstone at any time and with gallbladder
      surgery up to 1982 (OR from 2.7 to 1.3; all p < .001). Polyp occurrence was
      inversely associated with 1982 histories of high exercise level (men's OR 0.83;
      95% CI 0.76, 0.91; women's OR 0.90; 95% CI 0.78, 1.03), frequent aspirin use in
      women (OR 0.85; 95% CI 0.77, 0.95), and high parity in women (OR 0.84; 95% CI
      0.75, 0.94). Among participants lacking a clinically normal gallbladder, the
      polyp risks associated with smoking and high body mass index were reduced (p <
      .04 for interactions). CONCLUSIONS: Despite the limitations and potential biases
      in these self-reported data, the risk factors described here may be useful for
      identifying persons at modestly increased risk of having a colon polyp. The
      effect-modifying role of gallbladder status deserves further investigation.

PMID- 9613886
TI  - Risk of major hemorrhage for outpatients treated with warfarin.
AB  - OBJECTIVE: To determine the incidence of major hemorrhage among outpatients
      started on warfarin therapy after the recommendation in 1986 for reduced
      intensity anticoagulation therapy was made, and to identify baseline patient
      characteristics that predict those patients who will have a major hemorrhage.
      DESIGN: Retrospective cohort study. SETTING: A university-affiliated Veterans
      Affairs Medical Center. PATIENTS: Five hundred seventy-nine patients who were
      discharged from the hospital after being started on warfarin therapy.
      MEASUREMENTS AND MAIN RESULTS: The primary outcome variable was major hemorrhage.
      In our cohort of 579 patients, there were 40 first-time major hemorrhages with
      only one fatal bleed. The cumulative incidence was 7% at 1 year. The average
      monthly incidence of major hemorrhage was 0.82% during the first 3 months of
      treatment and decreased to 0.36% thereafter. Three independent predictors of
      major hemorrhage were identified: a history of alcohol abuse, chronic renal
      insufficiency, and a previous gastrointestinal bleed. Age, comorbidities,
      medications known to influence prothrombin levels, and baseline laboratory values
      were not associated with major hemorrhage. CONCLUSIONS: The incidence of major
      hemorrhage in this population of outpatients treated with warfarin was lower than
      previous estimates of major hemorrhage measured before the recommendation for
      reduced-intensity anticoagulation therapy was made, but still higher than
      estimates reported from clinical trials. Alcohol abuse, chronic renal
      insufficiency, and a previous gastrointestinal bleed were associated with
      increased risk of major hemorrhage.

PMID- 9613887
TI  - Improving in-training evaluation programs.

PMID- 9613888
TI  - Physicians' changing attitudes toward guidelines.
AB  - The objective of the study was to measure the change in physicians' attitudes
      toward preventive care guidelines over a 2-year period. The study was conducted
      at a Southern California managed care medical group that was experiencing intense
      price competition. We analyzed individualized survey responses of 62 HMO primary
      care physicians over the study period. We found that physicians increasingly
      believed that clinical guidelines were being used for cost containment (first
      survey 71% vs second survey 92%, p < .005) and less for quality improvement
      (first survey 85% vs second survey 67%, p < .008) over time. These findings may
      create a barrier to physicians' adoption of practice guidelines.

PMID- 9613889
TI  - Ambulatory versus inpatient rotations in teaching third-year students internal
      medicine.
AB  - We studied 63 randomly selected third-year students who split their 10-week
      medicine clerkship between ambulatory and inpatient components. Compared with
      their inpatient experience, during the ambulatory rotation, the 63 students felt
      more like doctors, more responsible for patients, and more able to know and help
      their patients. Students reported that ambulatory attending staff appeared
      happier and less stressed, and did not embarrass them as frequently. Compared
      with their 619 "inpatient" classmates, these 63 "ambulatory" students scored as
      well on the medicine examination, and were as likely to receive honors (44% vs
      41%), and to choose internal medicine residencies (35% vs 34%). In conclusion,
      students experienced better relationships with their patients and teachers during
      the ambulatory rotation, which was academically comparable to the inpatient
      experience.

PMID- 9613890
TI  - Will commercial managed care patients accept residents as their primary care
      providers?
AB  - We conducted a telephone survey of patients in a university-based medical
      practice to determine if there was a difference across payer class in patients'
      willingness to have supervised housestaff physicians function as their primary
      care providers. Overall, commercial managed care patients were more likely to
      object to seeing housestaff physicians than were Medicaid or Medicare patients
      (50% vs 32% or 23%, respectively). However, prior outpatient care by a resident
      physician significantly increased patient willingness to be cared for by a
      resident. This effect of prior care by a resident was noted in the managed care
      as well as the Medicaid and Medicare populations. Although there may have been
      self-selection, our data demonstrate that a significant proportion of managed
      care patients who have had residents as their primary care providers are amenable
      to continuing this practice.

PMID- 9613892
TI  - A review of journal clubs in postgraduate medical education.
AB  - OBJECTIVE: To review the goals, organization, and teaching methods of journal
      clubs, summarize elements of successful clubs, and evaluate their effect on
      reading habits, and effectiveness in meeting teaching goals. Examples of clubs
      that utilize principles of adult learning are reviewed. DATA SOURCES: English
      language articles identified through a MEDLINE search (1966-1997) using the MeSH
      terms "internship" and "residency," and text words "journal club" and "critical
      appraisal." STUDY SELECTION: Articles on learning goals and organization were
      included if they represented national or regional surveys with a response rate of
      65% or greater. Articles that evaluated teaching effectiveness were included if
      they used a controlled, educational design, or if they exemplified important
      adult learning principles. DATA EXTRACTION: Data were manually extracted from
      selected studies and reviews. DATA SYNTHESIS: A major goal for most clubs is to
      teach critical appraisal skills. Clubs with high attendance and longevity are
      characterized by mandatory attendance, availability of food, and perceived
      importance by the program director. Residents who are taught critical appraisal
      report paying more attention to the methods and are more skeptical of the
      conclusions, and have increased knowledge of clinical epidemiology and
      biostatistics, but studies have failed to demonstrate that these residents read
      more, or read more critically. Reading guidelines may be useful for teaching
      critical appraisal skills, and may be associated with increased resident
      satisfaction. CONCLUSIONS: Journal club formats are educationally diverse, can
      incorporate adult learning principles, and are an adaptable format for teaching
      the "new basic sciences."

PMID- 9613891
TI  - Evaluation and management of vaginitis.
AB  - OBJECTIVE: To evaluate recent advances in our understanding of the clinical
      relevance, diagnosis, and treatment of vaginal infections, and to determine an
      efficient and effective method of evaluating this clinical problem in the
      outpatient setting. DATA SOURCES: Relevant papers on vaginitis limited to the
      English language obtained through a MEDLINE search for the years 1985 to 1997
      were reviewed. DATA SYNTHESIS: Techniques that enable the identification of the
      various strains of candida have helped lead to a better understanding of the
      mechanisms of recurrent candida infection. From this information a rationale for
      the treatment of recurrent disease can be developed. Bacterial vaginosis has been
      associated with complications, including upper genital tract infection, preterm
      delivery, and wound infection. Women undergoing pelvic surgery, procedures in
      pregnancy, or pregnant women at risk of preterm delivery should be evaluated for
      bacterial vaginosis to decrease the rate of complications associated with this
      condition. New, more standardized criteria for the diagnosis of bacterial
      vaginosis may improve diagnostic consistency among clinicians and comparability
      of study results. Use of topical therapies in the treatment of bacterial
      vaginosis are effective and associated with fewer side effects than systemic
      medication. Trichomonas vaginalis, although decreasing in incidence, has been
      associated with upper genital tract infection. Therapy of T. vaginalis infection
      has been complicated by an increasing incidence of resistance to metronidazole.
      CONCLUSIONS: Vaginitis is a common medical problem in women that is associated
      with significant morbidity and previously unrecognized complications. Research in
      recent years has improved diagnostic tools as well as treatment modalities for
      all forms of vaginitis.

PMID- 9613893
TI  - "Treatment" cosmetics: hype or help?

PMID- 9613894
TI  - Trial suggests change in transfusion strategy.

PMID- 9613895
TI  - "Blood soup" and bear exams acquaint kids with hospitals.

PMID- 9613896
TI  - From the Centers for Disease Control and Prevention. Fatal occupational injuries-
      United States, 1980-1994.

PMID- 9613897
TI  - From the Centers for Disease Control and Prevention. Surveillance for nonfatal
      occupational injuries treated in hospital emergency departments--United States,
      1996.

PMID- 9613898
TI  - From the Centers for Disease Control and Prevention. Demographic characteristics
      of persons without a regular source of medical care--selected states, 1995.

PMID- 9613899
TI  - Risk factors for ICU-acquired pneumonia.

PMID- 9613900
TI  - A piece of my mind. The ungifted physician.

PMID- 9613901
TI  - On being a physician: choices, sacrifice, and balance.

PMID- 9613902
TI  - On being a physician: choices, sacrifice, and balance.

PMID- 9613903
TI  - Perioperative blood transfusion.

PMID- 9613904
TI  - Leisure-time physical activity and mortality: how is sausage made?

PMID- 9613905
TI  - Health values of hospitalized elderly patients.

PMID- 9613906
TI  - Health values of hospitalized elderly patients.

PMID- 9613907
TI  - Genetic testing for susceptibility to cancer. Task Force on Cancer Genetics
      Education.

PMID- 9613908
TI  - Insulin use by bodybuilders.

PMID- 9613909
TI  - Toxic epidermal necrolysis from atorvastatin.

PMID- 9613910
TI  - Primary prevention of acute coronary events with lovastatin in men and women with
      average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary
      Atherosclerosis Prevention Study.
AB  - CONTEXT: Although cholesterol-reducing treatment has been shown to reduce fatal
      and nonfatal coronary disease in patients with coronary heart disease (CHD), it
      is unknown whether benefit from the reduction of low-density lipoprotein
      cholesterol (LDL-C) in patients without CHD extends to individuals with average
      serum cholesterol levels, women, and older persons. OBJECTIVE: To compare
      lovastatin with placebo for prevention of the first acute major coronary event in
      men and women without clinically evident atherosclerotic cardiovascular disease
      with average total cholesterol (TC) and LDL-C levels and below-average high
      density lipoprotein cholesterol (HDL-C) levels. DESIGN: A randomized, double
      blind, placebo-controlled trial. SETTING: Outpatient clinics in Texas.
      PARTICIPANTS: A total of 5608 men and 997 women with average TC and LDL-C and
      below-average HDL-C (as characterized by lipid percentiles for an age- and sex
      matched cohort without cardiovascular disease from the National Health and
      Nutrition Examination Survey [NHANES] III). Mean (SD) TC level was 5.71 (0.54)
      mmol/L (221 [21] mg/dL) (51 st percentile), mean (SD) LDL-C level was 3.89 (0.43)
      mmol/L (150 [17] mg/dL) (60th percentile), mean (SD) HDL-C level was 0.94 (0.14)
      mmol/L (36 [5] mg/dL) for men and 1.03 (0.14) mmol/L (40 [5] mg/dL) for women
      (25th and 16th percentiles, respectively), and median (SD) triglyceride levels
      were 1.78 (0.86) mmol/L (158 [76] mg/dL) (63rd percentile). INTERVENTION:
      Lovastatin (20-40 mg daily) or placebo in addition to a low-saturated fat, low
      cholesterol diet. MAIN OUTCOME MEASURES: First acute major coronary event defined
      as fatal or nonfatal myocardial infarction, unstable angina, or sudden cardiac
      death. RESULTS: After an average follow-up of 5.2 years, lovastatin reduced the
      incidence of first acute major coronary events (1 83 vs 116 first events;
      relative risk [RR], 0.63; 95% confidence interval [CI], 0.50-0.79; P<.001),
      myocardial infarction (95 vs 57 myocardial infarctions; RR, 0.60; 95% CI, 0.43
      0.83; P=.002), unstable angina (87 vs 60 first unstable angina events; RR, 0.68;
      95% CI, 0.49-0.95; P=.02), coronary revascularization procedures (157 vs 106
      procedures; RR, 0.67; 95% CI, 0.52-0.85; P=.001), coronary events (215 vs 163
      coronary events; RR, 0.75; 95% CI, 0.61-0.92; P =.006), and cardiovascular events
      (255 vs 194 cardiovascular events; RR, 0.75; 95% CI, 0.62-0.91; P = .003).
      Lovastatin (20-40 mg daily) reduced LDL-C by 25% to 2.96 mmol/L (115 mg/dL) and
      increased HDL-C by 6% to 1.02 mmol/L (39 mg/dL). There were no clinically
      relevant differences in safety parameters between treatment groups. CONCLUSIONS:
      Lovastatin reduces the risk for the first acute major coronary event in men and
      women with average TC and LDL-C levels and below-average HDL-C levels. These
      findings support the inclusion of HDL-C in risk-factor assessment, confirm the
      benefit of LDL-C reduction to a target goal, and suggest the need for
      reassessment of the National Cholesterol Education Program guidelines regarding
      pharmacological intervention.

PMID- 9613911
TI  - The changing pattern of prenatal care utilization in the United States, 1981
      1995, using different prenatal care indices.
AB  - CONTEXT: Two measures traditionally used to examine adequacy of prenatal care
      indicate that prenatal care utilization remained unchanged through the 1980s and
      only began to rise slightly in the 1990s. In recent years, new measures have been
      developed that include a category for women who receive more than the recommended
      amount of care (intensive utilization). OBJECTIVE: To compare the older and newer
      indices in the monitoring of prenatal care trends in the United States from 1981
      to 1995, for the overall population and for selected subpopulations. Second, to
      examine factors associated with receiving intensive utilization. DESIGN: Cross
      sectional and trend analysis of national birth records. SETTING: The United
      States. SUBJECTS: All live births between 1981 and 1995 (N=54 million). MAIN
      OUTCOME MEASURES: Trends in prenatal care utilization, according to 4 indices
      (the older indices: the Institute of Medicine Index and the trimester that care
      began, and the newer indices: the R-GINDEX and the Adequacy of Prenatal Care
      Utilization Index). Multiple logistic regression was used to assess the risk of
      intensive prenatal care use in 1981 and 1995. RESULTS: The newer indices showed a
      steadily increasing trend toward more prenatal care use throughout the study
      period (R-GINDEX, intensive or adequate use, 32.7% in 1981 to 47.1 % in 1995; the
      Adequacy of Prenatal Care Utilization Index, intensive use, 18.4% in 1981 to
      28.8% in 1995), especially for intensive utilization. Women having a multiple
      birth were much more likely to have had intensive utilization in 1995 compared
      with 1981 (R-GINDEX, 22.8% vs 8.5%). Teenagers were more likely to begin care
      later than adults, but similar proportions of teens and adults had intensive
      utilization. Intensive use among low-risk women also increased steadily each
      year. Factors associated with a greater likelihood of receiving intensive use in
      1981 and 1995 were having a multiple birth, primiparity, being married, and
      maternal age of 35 years or older. CONCLUSIONS: The proportion of women who began
      care early and received at least the recommended number of visits increased
      between 1981 and 1995. This change was undetected by more traditional prenatal
      care indices. These increases have cost and practice implications and suggest a
      paradox since previous studies have shown that rates of preterm delivery and low
      birth weight did not improve during this time.

PMID- 9613912
TI  - Nebulized budesonide and oral dexamethasone for treatment of croup: a randomized
      controlled trial.
AB  - CONTEXT: The effectiveness of glucocorticoids for patients with croup is well
      established but it remains uncertain which glucocorticoid regimen is most
      effective. OBJECTIVE: To determine the effectiveness of 3 glucocorticoid regimens
      in patients with croup. DESIGN: Randomized controlled trial with parallel design.
      SETTING: Emergency departments of 2 Canadian pediatric tertiary care hospitals.
      PARTICIPANTS: Children with a clinical syndrome consistent with croup, aged 3
      months to 5 years, with a croup score of 2 or greater following at least 15
      minutes of mist therapy. INTERVENTIONS: Oral dexamethasone, 0.6 mg/kg, and
      nebulized placebo; oral placebo and nebulized budesonide, 2 mg; or oral
      dexamethasone, 0.6 mg/kg, and nebulized budesonide, 2 mg. MAIN OUTCOME MEASURES:
      Westley croup score (primary outcome), hospital admission rates, time spent in
      the emergency department, return visits to the emergency department, or ongoing
      symptoms at 1 week. RESULTS: The mean change in the croup score from baseline to
      the final study assessment was -2.3 (95% confidence interval [CI], -2.6 to -2.0)
      in the budesonide group (n = 65), -2.4 (95% CI, -2.6 to -2.2) in the
      dexamethasone group (n = 69), and -2.4 (95% CI, -2.7 to -2.1) in the budesonide
      and dexamethasone group (n = 64, P = .70). CONCLUSIONS: Based on the similar
      outcomes in the 3 groups, oral dexamethasone is the preferred intervention
      because of its ease of administration, lower cost, and more widespread
      availability.

PMID- 9613913
TI  - Fatal residential fires: who dies and who survives?
AB  - CONTEXT: The United States has one of the highest fire fatality rates in the
      developed world, and three quarters of these deaths are in residential fires.
      OBJECTIVE: To compare characteristics of those who die and those who survive in
      the same residential fire. DESIGN: Data on fatal residential fires were collected
      from the medical examiner and interviews with local fire officials. SETTING:
      North Carolina. SUBJECTS: Persons in residential fires with at least 1 fatality
      in a 1-year period. MAIN OUTCOME MEASURE: Dying vs surviving a fatal residential
      fire that occurred with more than 1 person at home. RESULTS: Of the 190
      decedents, 124 (65%) were male, 78 (41%) were home alone, and 69 (53%) of 130
      adults who had blood alcohol measured were intoxicated (blood alcohol content >22
      mmol/L [100 mg/dL]). Of the 254 persons present during fires in which more than 1
      person was at home, 112 died. Individuals more likely to die (high-vulnerability
      group) were younger than 5 years or 64 years or older, had a physical or
      cognitive disability, or were impaired by alcohol or other drugs (risk of death
      for group, odds ratio [OR], 4.01; 95% confidence interval [CI], 2.29-7.03). The
      presence of an adult with no physical or cognitive disabilities who was
      unimpaired by alcohol or other drugs (a potential rescuer) reduced the risk of
      death in the high-vulnerability group (OR, 0.49; 95% CI, 0.24-0.99) but not the
      low-vulnerability group. Overall, a functioning smoke detector lowered the risk
      of death (OR, 0.39; 95% CI, 0.18-0.83). CONCLUSIONS: Smoke detectors were equally
      effective in both low- and high-vulnerability populations. The high-vulnerability
      group was more likely to survive if, in addition to a smoke detector, a potential
      rescuer was present. Further research should seek to identify prompts that
      facilitate speedy egress from a burning structure and that can be incorporated
      into residential fire alarm systems.

PMID- 9613914
TI  - Use of public performance reports: a survey of patients undergoing cardiac
      surgery.
AB  - CONTEXT: Publicly released performance reports ("report cards") are expected to
      foster competition on the basis of quality. Proponents frequently cite the need
      to inform patient choice of physicians and hospitals as a central element of this
      strategy. OBJECTIVE: To examine the awareness and use of a statewide consumer
      guide that provides risk-adjusted, in-hospital mortality ratings of hospitals
      that provide cardiac surgery. DESIGN: Telephone survey conducted in 1996.
      SETTING: Pennsylvania, where since 1992, the Pennsylvania Consumer Guide to
      Coronary Artery Bypass Graft [CABG] Surgery has provided risk-adjusted mortality
      ratings of all cardiac surgeons and hospitals in the state. PARTICIPANTS: A total
      of 474 (70%) of 673 eligible patients who had undergone CABG surgery during the
      previous year at 1 of 4 hospitals listed in the Consumer Guide as having average
      mortality rates between 1% and 5% were successfully contacted. MAIN OUTCOME
      MEASURES: Patients' awareness of the Consumer Guide, their knowledge of its
      ratings, their degree of interest in the report, and barriers to its use.
      RESULTS: Ninety-three patients (20%) were aware of the Consumer Guide, but only
      56 (12%) knew about it before surgery. Among these 56 patients, 18 reported
      knowing the hospital rating and 7 reported knowing the surgeon rating, 11 said
      hospital and/or surgeon ratings had a moderate or major impact on their decision
      making, but only 4 were able to specify either or both correctly. When the
      Consumer Guide was described to all patients, 264 (56%) were "very" or "somewhat"
      interested in seeing a copy, and 273 (58%) reported that they probably or
      definitely would change surgeons if they learned that their surgeon had a higher
      than expected mortality rate in the previous year. A short time window for
      decision making and a limited awareness of alternative hospitals within a
      reasonable distance of home were identified as important barriers to use.
      CONCLUSIONS: Only 12% of patients surveyed reported awareness of a prominent
      report on cardiac surgery mortality before undergoing cardiac surgery. Fewer than
      1% knew the correct rating of their surgeon or hospital and reported that it had
      a moderate or major impact on their selection of provider. Efforts to aid patient
      decision making with performance reports are unlikely to succeed without a
      tailored and intensive program for dissemination and patient education.

PMID- 9613915
TI  - Antiatherothrombotic properties of statins: implications for cardiovascular event
      reduction.
AB  - Clinical trials of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase
      inhibitors or statin therapy have demonstrated that baseline or treated low
      density lipoprotein (LDL) cholesterol levels are only weakly associated with net
      coronary angiographic change or cardiovascular events. The beneficial effects of
      statins on clinical events may involve nonlipid mechanisms that modify
      endothelial function, inflammatory responses, plaque stability, and thrombus
      formation. Experimental animal models suggest that statins may foster stability
      through a reduction in macrophages and cholesterol ester content and an increase
      in volume of collagen and smooth muscle cells. The thrombotic sequelae caused by
      plaque disruption is mitigated by statins through inhibition of platelet
      aggregation and maintenance of a favorable balance between prothrombotic and
      fibrinolytic mechanisms. These nonlipid properties of statins may help to explain
      the early and significant cardiovascular event reduction reported in several
      clinical trials of statin therapy.

PMID- 9613916
TI  - A 40-year-old woman considering contraception.

PMID- 9613917
TI  - A 37-year-old man with multiple somatic complaints, 1 year later.

PMID- 9613918
TI  - Lipid-lowering therapy in low-risk patients.

PMID- 9613919
TI  - Benefits and limitations of prenatal care: from counting visits to measuring
      content.

PMID- 9613921
TI  - Proteoglycans in human coronary arteriosclerotic lesions.
AB  - Proteoglycans in human coronary arteries were characterized
      immunohistochemically, using specific monoclonal antibodies to distinct
      proteoglycan types. In addition, apoB, macrophage, and arterial smooth muscle
      cell alpha-actin markers were localized. The expression of chondroitin sulfate
      proteoglycans and apoB was observed in healthy areas (operationally defined by
      morphology) as well as in lesions in the intima, but with greater expression in
      the atheromatous lesions. In healthy intima heparan sulfate proteoglycan was cell
      associated, but in lesions it was found also in the extracellular space. A
      dermatan sulfate proteoglycan of decorin type was not observed in the healthy
      intima but was observed in the intima with adaptive thickening especially in
      zones with reduced staining for smooth muscle cell alpha-actin. In atheroma
      (fibrous plaque with necrotic core) decorin along with alpha-actin and macrophage
      marker stained brightly in the extracellular regions in fibrous cap (actively
      progressing lesion) but was sparse in fibrous base (quiescent lesion). The
      observations suggest that decorin along with extracellular alpha-actin and
      macrophage marker may be useful for differentiating lesions that tend to progress
      with disease.

PMID- 9613922
TI  - Colchicine, like methylprednisolone, decreases the perilesional fibrosis
      secondary to a chronic brain granuloma in cats.
AB  - We studied the effects of long-term administration of colchicine on the fibrosis
      surrounding a granulomatous lesion previously induced by stereotactic injection
      of aluminum silicate into the brain parenchyma of cats. Every week the animals
      received a single i.m. injection of colchicine (0.25 mg), or methylprednisolone
      (4 mg), or saline solution (controls) for 6 months. The mean area of fibrosis in
      animals treated with colchicine or with methylprednisolone was smaller than that
      of control animals (P < 0.05). In controls, a dense capsule of procollagen and
      collagen fibers was found around the granuloma, and myelinated neurites were
      scarce, whereas in animals treated with colchicine or with methylprednisolone the
      capsule and fibers were thinner and more myelinated neurites remained. These
      changes were more evident in animals treated with colchicine. Our results suggest
      that chronic administration of colchicine or methylprednisolone limit the
      fibrosis and histological damage around a granulomatous lesion of the brain.

PMID- 9613923
TI  - The effects of glutathione glycoside in acetaminophen-induced liver cell
      necrosis.
AB  - The hepatotoxic effects of high-dose acetaminophen (400 and 600 mg/kg body
      weight) were evaluated by determining the glutathione (GSH) and malondialdehyde
      (MDA) levels and the histological changes in the liver at 6 and 12 h, using
      C57BL/6J mice. Massive centrilobular hepatocyte necrosis associated with severe
      reduction of liver GSH and a significant increase in MDA levels were observed
      following acetaminophen intoxication. Administration of glutathione glycoside
      (GSH-glyc), a compound newly synthesized in our laboratory, 2 h after
      acetaminophen injection prevented changes in the GSH and MDA preserving their
      levels nearly to those of controls; in addition, histological evidence of
      hepatocyte necrosis was either abolished or severely reduced in the majority of
      animals. GSH-glyc is a nontoxic compound that can be used to transport GSH into
      cells, including those of brain and liver, and may prove to be useful for the
      prophylaxis and therapy of toxic tissue injury, including that induced by
      overdosage of acetaminophen.

PMID- 9613924
TI  - The response of hepatic acute phase proteins during experimental pulmonary
      tuberculosis.
AB  - A mouse model of pulmonary tuberculosis induced by the intratracheal instillation
      of live and virulent mycobacteria strain H37-Rv was used to study the
      relationship of the histopathological changes with the kinetics of local
      production and circulating levels of interleukin 6 (IL-6) and the gene expression
      of acute phase proteins (APP) in the liver. The histopathological studies showed
      a mononuclear inflammatory infiltrate located in the perivascular, peribronchial,
      and interstitial areas, with granulomas which started to form 2 weeks after the
      infection. Numerous IL-6 immunostained activated macrophages were observed in the
      inflammatory infiltrate, particularly in the interstitial-intralveolar
      compartment and granulomas, coexisting with a high IL-6 mRNA concentration
      determined by reverse transcription polimerase chain reaction in lung
      homogenates, particularly at day 21 of infection. Two peaks of IL-6 demonstrated
      by ELISA in lung homogenates and sera were observed at day 3 and 21 of infection,
      being higher on the latter. The hepatic APP mRNA transcription (alpha1-acid
      glycoprotein, fibrinogen, complement factor 4) analyzed by Northern blot showed a
      rapid and high increase at day one postinfection, which rapidly decreased and
      showed another second peak at day 21, when granulomas reached full maturity and
      the maximal production of IL-6 was observed. At the same time the liver mRNA
      concentrations of the negative APP albumin showed a substantial decrease. From 1
      to 4 months after M. tuberculosis intratracheal instillation, histopathological
      changes of more severity (pneumonia, necrosis) and chronicity (interstitial
      fibrosis) were seen, as well as small groups of IL-6 immunostained macrophages in
      the pneumonic areas, granulomas and perivascular compartments, in coexistence
      with low IL-6 expression. During this advanced stage of the disease a high mRNA
      concentration of alpha1-acid glycoprotein and fibrinogen associated with low
      expression of the albumin gene in the liver continued. Thus, it seems that the
      time course of hepatic APP genetic expression in experimental pulmonary
      tuberculosis is related to the production of IL-6 and relevant histopathological
      changes, particularly the formation of granuloma.

PMID- 9613925
TI  - Microautoradiographic quantitation of vascular endothelial growth factor mRNA
      levels in human prostate specimens containing normal and neoplastic epithelium.
AB  - Human prostate specimens commonly contain a spectrum of epithelial changes,
      including normal acinar and ductal structures, hyperplasia, intraepithelial
      neoplasia (dysplasia), and carcinoma. Since vascular endothelial growth factor
      (VEGF) expression is dependent on cell type and tissue microenvironment,
      meaningful quantitation of the levels of this mRNA in pathological specimens
      requires analysis at the microscopic level. Phosphorimage analysis of the binding
      of radiolabeled cRNA probes to tissue sections allows quantitation of mRNA
      levels, but the resolution is limited. Alternatively, emulsion autoradiography
      allows visualization of mRNA levels at cellular resolution, but quantitation is
      difficult. We have developed a method of quantitating steady state mRNA levels in
      tissue sections at the microscopic level, using autoradiography and quantitative
      image analysis. In this study, we describe the method and apply it to
      quantitation of VEGF mRNA in human prostate specimens. The VEGF mRNA level was
      low in nonepithelial stromal tissue (0.8 dpm/mm2), high in normal and benign
      hyperplastic epithelium (17-18 dpm/mm2), and significantly decreased in
      intraepithelial neoplasia (6.4 dpm/mm2) and in microacinar carcinoma that had
      invaded the stroma (3.5 dpm/mm2). Immunohistochemical staining detected VEGF
      protein in epithelial and stromal cells, with highest levels on the luminal
      surface of normal epithelium and in stromal cells, and lower levels in benign
      hyperplasia, intraepithelial neoplasia, and carcinoma. No correlation between
      VEGF expression in epithelium and nearby vessel density was observed. The results
      indicate a decrease in the steady state level of VEGF mRNA when prostate
      epithelial cells become transformed, escape the confines of glandular structure
      and invade the stroma, and suggest that the progression of prostatic carcinoma
      through the stages examined in this study is not associated with increased VEGF
      expression, in contrast to the elevated VEGF expression associated with
      progression of several other tumor types.

PMID- 9613926
TI  - Requirements for initial assay validation and publication in J. Chromatography B.

PMID- 9613927
TI  - Disposable, enzymatically modified printed film carbon electrodes for use in the
      high-performance liquid chromatographic-electrochemical detection of glucose or
      hydrogen peroxide from immobilized enzyme reactors.
AB  - Disposable screen-printed, film carbon electrodes (PFCE) were modified with cast
      coated Osmium-polyvinylpyrridine-wired horse radish peroxidase gel polymer (Os
      gel-HRP) to enable the detection of the reduction at 0 mV of hydrogen peroxide
      (H2O2) derived from a post-column immobilized enzyme reactor (IMER) containing
      acetylcholinesterase and choline oxidase. In another series of experiments PFCE
      were initially modified with cast-coated Os-gel-HRP and then treated with glucose
      oxidase in bovine serum albumin (BSA) and cross-linked with glutaraldehyde to
      form a bi-layer glucose-Os-gel-HRP PFCE. This bi-layer glucose-Os-gel-HRP PFCE
      generated a reduction current at 0 mV to H2O2 derived from the reaction of
      glucose oxidase and glucose in solution. These enzyme-modified PFCE were housed
      in a radial flow cell and coupled with cation-exchange liquid chromatographic
      methods to temporally separate substrates in solution for the determination of
      acetylcholine (ACh) and choline (Ch) in the first experimental series, or glucose
      in the second experimental series. These two disposable enzyme-modified PFCE
      exhibited linear current vs. substrate relations, were durable, being usable for
      approximately 40 determinations, and were sufficiently sensitive to be employed
      in biological sampling. Both assays utilized the same HPLC equipment. The limit
      of detection for ACh was 16 fmol/10 microl and that for glucose was 12
      micromol/7.5 microl. ACh and Ch were measured from a microdialysate from the
      frontal cortex of a rat. Glucose in human urine was determined using the bi-layer
      glucose oxidase-Os-gel-HRP PFCE.

PMID- 9613928
TI  - Separate determination of human urinary conjugated and unconjugated 3-methoxy-4
      hydroxyphenylethyleneglycol.
AB  - A new determination procedure for human urinary 3-methoxy-4
      hydroxyphenylethyleneglycol (MHPG) was established. In addition to the previously
      established solid-phase extraction method for unconjugated MHPG, another solid
      phase extraction method for conjugated MHPG was developed. Unconjugated MHPG was
      adsorbed on a Sep-Pak Diol cartridge and selectively recovered by elution with
      ethyl acetate. The eluate was evaporated and the residue was redissolved and
      analyzed by reversed-phase high-performance liquid chromatography with
      fluorimetric detection. Conjugated (sulfate plus glucuronide) MHPG was adsorbed
      on a Sep-Pak Accell QMA cartridge and quantitatively eluted with 0.2 M NaCl.
      After enzymatic hydrolysis, deconjugated MHPG was extracted using a Sep-Pak Diol
      cartridge and analyzed in the same manner as unconjugated MHPG. The new method is
      simple and rapid and can quantitate conjugated and unconjugated MHPG
      discriminatively.

PMID- 9613929
TI  - Separation of metalloprotein complexes in serum by size-exclusion chromatography.
      Optimisation of the separation parameters retention behaviour and recovery
      employing radiotracers.
AB  - A suitable procedure was developed for speciation analysis of metalloprotein
      complexes in serum using directly coupled size-exclusion chromatography and an
      element-specific detector. Two column matrices used for size-exclusion
      chromatography (TSK G 3000 SW and Asahipak GS 520) were investigated with respect
      to the recovery and retention behaviour for metalloprotein complexes.
      Optimisation of the separation parameters (buffer type, concentration, pH) was
      achieved by means of metalloprotein complexes marked with radiotracers. For
      speciation of serum the matrix in the Asahipak GS column is more efficient. Given
      optimal eluent characteristics (100 mM Tris, pH 7.4) the recovery of the elements
      investigated (sodium, calcium, iron and zinc) was 100%. Further, the retention
      behaviour (retention time, ratios of the peak areas) remained unchanged for
      several successive separations.

PMID- 9613930
TI  - Bilirubin removal from human plasma in a packed-bed column system with dye
      affinity microbeads.
AB  - A dye-ligand. Cibacron Blue F3GA. was covalently coupled with the poly(EGDMA
      HEMA) microbeads. The affinity sorbent carrying 16.5 micromol Cibacron Blue F3GA
      per gram polymer was then used to remove bilirubin from human plasma in a packed
      bed column system. Bilirubin adsorption from human plasma on the unmodified
      poly(EGDMA-HEMA) microbeads was 0.32 mg/g, while much higher adsorption values,
      up to 24.2 mg/g, were obtained with the dye-attached microbeads. The bilirubin
      adsorption capacity of the microbeads decreased with an increase in the
      recirculation rate of plasma. Bilirubin adsorption increased with increasing
      temperature, and the maximum adsorption achieved at 37 degrees C (32.5 mg
      bilirubin/g polymer). Bilirubin molecules interacted directly with the
      immobilized Cibacron Blue F3GA molecules. Contribution of albumin adsorption on
      bilirubin adsorption was also significant.

PMID- 9613931
TI  - Simultaneous measurement of adenosine and hypoxanthine in human umbilical cord
      plasma using reversed-phase high-performance liquid chromatography with
      photodiode-array detection and on-line validation of peak purity.
AB  - A new, robust and sensitive reversed-phase high-performance liquid
      chromatographic method was developed for concomitant measurement of plasma
      concentrations of the ATP catabolites adenosine and hypoxanthine in human
      umbilical cord blood. Deproteinized cord plasma was chromatographed on Hypersil
      C18 columns, using UV photodiode-array detection, spectral analysis of peaks and
      on-line confirmation of peak purity. Elution with a gradient of acetonitrile
      tetrahydrofuran in ammonium dihydrogen phosphate buffer pH 4.7, yielded sharp,
      well-resolved peaks of adenosine and hypoxanthine within 16 min. Peak areas were
      quantified from external calibration curves and converted to plasma
      concentrations via cord blood hematocrits. In seven deliveries, gestational ages
      32-40 weeks, adenosine (range, 0.1-2.1 microM) was less than hypoxanthine (range,
      1.6-18.5 microM) in the same cord plasma sample. Arteriovenous levels of each
      purine were similar, except in an abruptio placenta delivery.

PMID- 9613932
TI  - Quantification of intracellular levels of cyclic ADP-ribose by high-performance
      liquid chromatography.
AB  - A combined two-step high-performance liquid chromatographic (HPLC) method was
      developed for the analysis of endogenous levels of cyclic adenosine
      diphosphoribose (cADPR) in cell extracts. The detection sensitivity for cADPR was
      about 10 pmol. Linearity of the HPLC detection system was demonstrated in the
      range of 10 pmol up to 2 nmol. The method was validated in terms of within-day
      and between-day reproducibility of retention times and peak areas of standard
      nucleotides. The method was applied to the analysis of endogenous cADPR in human
      T cell lines. Sequential separation of perchloric acid extracts from cells on
      strong anion-exchange and reversed-phase ion-pair HPLC resulted in a single
      symmetrical peak co-eluting with standard cADPR. The identity of this endogenous
      material was further confirmed by its ability to be converted to ADPR upon
      heating the cell samples at 80 degrees C for 2 h. Recoveries of the combined
      perchloric acid extraction-HPLC analysis procedures were 48.3 +/- 10.2%. The
      determined intracellular concentrations of cADPR in quiescent Jurkat and HPB. ALL
      human T cells were 198 +/- 41 and 28 +/- 9 pmol/10(8) cells, respectively. In
      conclusion, a non-radioactive HPLC method presenting a specificity and
      sensitivity suitable for precise quantification of cADPR in cell extracts was
      developed.

PMID- 9613933
TI  - Determination of malondialdehyde in rat brain by capillary zone electrophoresis.
AB  - A method for determination of malondialdehyde with capillary electrophoresis
      using UV detection at 267 nm has been developed. The buffer system consisted of
      10 mM borax and 0.5 mM CTAB at pH 9.3. Malondialdehyde migrated as the first peak
      in the electropherogram at 2.6 min. Limit of detection was 1.2 microM
      corresponding to 7.8 pg. Malondialdehyde was determined before and after
      stimulating lipid peroxidation with the addition of ferrous ammonium sulphate to
      homogenates of rat brain tissue. Proteins were precipitated by boiling and
      removed from the brain homogenates with centrifugation. No further pretreatment
      was made before injecting the homogenates on the CE system. Non-precipitated
      homogenates could also be analyzed, but this required washing of the capillary
      with 0.1 M NaOH before introduction of the next sample.

PMID- 9613934
TI  - Determination of the amino acid neurotransmitters in the dorsal root ganglion of
      the rat by capillary electrophoresis with a laser-induced fluorescence-charge
      coupled device.
AB  - A sensitive, rapid and accurate analysis of the amino acid neurotransmitters in
      dorsal root ganglion (DRG) of rat was accomplished by capillary electrophoresis
      with a laser-induced fluorescence-charged coupled device (LIF-CCD) and
      fluorescein isothiocyanate (FITC) derivatization. Since the CCD is an image
      detector with a matrix array of photoelements, the photogenerated charge
      generated from single photoelements was summed up by on-chip charge binning, and
      used to improve the detection sensitivity. A self-compiled data processing
      program was used to calculate digitally the summation of the multiwavelength data
      and transform three-dimensional electropherograms into two-dimensional
      electropherograms. Use of this program improved the detection sensitivity, the
      extraction of useful statistical data and the performance of the quantitative
      analysis. Owing to its excellent detectability and the unique characteristic of
      its two-dimensional format, which allows to perform analog and digital summation,
      high detection sensitivity with detection limits ranging from 1.2 to 17.2 nM was
      obtained for the amino acid neurotransmitters by LIF-CCD. This method was
      demonstrated to be a powerful tool for analyzing the complex biological samples
      through quantitative determination of the six amino acid neurotransmitters in the
      DRG of rat.

PMID- 9613935
TI  - Reversed-phase gradient high-performance liquid chromatographic procedure for
      simultaneous analysis of very polar to nonpolar retinoids, carotenoids and
      tocopherols in animal and plant samples.
AB  - A reversed-phase gradient high-performance liquid chromatographic (HPLC)
      procedure, which utilizes gradient elution and detection by a photodiode-array
      detector, has been developed to analyze simultaneously very polar retinoids, such
      as 4-oxo-retinoyl-beta-glucuronide, retinoyl beta-glucuronide and 4-oxo-retinoic
      acid; polar retinoids, such as retinoic acid and retinol; nonpolar retinoids,
      such as retinyl esters; along with xanthophylls, monohydroxy carotenoids,
      hydrocarbon carotenoids, and tocopherols. The procedure has been applied to the
      simultaneous analysis of retinoids, carotenoids, and tocopherols present in human
      serum and liver, rat serum and tissues, and for carotenoids in a number of fruits
      and vegetables. Bilirubin present in human serum can also be simultaneously
      analyzed. By this gradient HPLC procedure, 3.4-didehydroretinyl ester (vitamin A2
      ester) has been identified as a minor constituent in a human liver sample.
      Lycopene was identified as a major carotenoid in one specimen of papaya fruit,
      and 5,6,5',6'-diepoxy-beta-carotene was characterized as a major carotenoid in
      one specimen of mango fruit.

PMID- 9613936
TI  - Column-switching high-performance liquid chromatographic assay for the
      determination of quercetin in human urine with ultraviolet absorbance detection.
AB  - A high-performance liquid chromatographic method is described for the
      determination of quercetin in human urine using column-switching and ultraviolet
      (UV) absorbance detection. Urine samples were enzymatically hydrolysed and solid
      phase extracted prior to injection onto the high-performance liquid
      chromatography (HPLC) system. Prior to elution of quercetin and the internal
      standard, fisetin. from the first column used for sample clean-up, the six-port
      valve was switched to the second column for analysis with UV detection. Detection
      of quercetin was accurate and reproducible, with a detection limit of 5 ng/ml.
      The method was applied to determine the urinary level of quercetin in 120 samples
      from an intervention study with fruit juice.

PMID- 9613937
TI  - Application of solid-phase microextraction and gas chromatography-mass
      spectrometry for the determination of chlorophenols in urine.
AB  - This study investigated the feasibility of applying solid-phase microextraction
      (SPME) combined with gas chromatography-mass spectrometry to analyze
      chlorophenols in urine. The SPME experimental procedures to extract chlorophenols
      in urine were optimized with a polar polyacrylate coated fiber at pH 1,
      extraction time for 50 min and desorption in GC injector at 290 degrees C for 2
      min. The linearity was obtained with a precision below 10% R.S.D. for the studied
      chlorophenols in a wide range from 0.1 to 100 microg/l. In addition, sample
      extraction by SPME was used to estimate the detection limits of chlorophenols in
      urine, with selected ion monitoring of GC-MS operated in the electron impact mode
      and negative chemical ionization mode. Detection limits were obtained at the low
      ng/l levels. The application of the methods to the determination of chlorophenols
      in real samples was tested by analyzing urine samples of sawmill workers. The
      chlorophenols were found in workers, the urinary concentration ranging from 0.02
      microg/l (PCP) to 1.56 microg/l (2,4-DCP) depending on chlorophenols. The results
      show that trace chlorophenols have been detected with SPME-GC-MS in the workers
      of sawmill where chlorophenol-containing anti-stain agents had been previously
      used.

PMID- 9613938
TI  - Determination of amphetamine and methamphetamine in human hair by headspace solid
      phase microextraction and gas chromatography with nitrogen-phosphorus detection.
AB  - A simple and rapid method for the determination of amphetamine (AP) and
      methamphetamine (MA) in human hair was developed by headspace solid-phase
      microextraction (SPME) and gas chromatography with nitrogen-phosphorus detection
      (GC-NPD). The hair (1 mg) was dissolved in 0.2 ml of a 5 M sodium hydroxide
      solution in a tightly sealed vial by shaking at 75 degrees C for about 5 min. In
      order to adsorb AP and MA on the SPME fiber, 100 microm of polydimethylsiloxane
      fiber was exposed to the headspace of the vial, and the vial was heated at 55
      degrees C for 20 min. Then the fiber was removed from the vial and inserted into
      the injection port of the GC-NPD system using a CBJ-17 capillary column. The
      compounds adsorbed on the fiber were analyzed by exposing the fiber at 220
      degrees C for 30 s in the GC injection port. By using this method, AP and MA in
      human hair could be analyzed simply and rapidly without any interference from
      coexisting substances. The percentages of AP and MA extracted from human hair by
      the SPME method were 48 and 62%, respectively, and relative standard deviations
      were below 10% (n=5). The calibration curves for AP and MA were linear in the
      ranges of 0.4-15 and 4-160 ng/mg hair, respectively. The detection limits of AP
      and MA at a signal-to-noise ratio of three were 0.1 and 0.4 ng/mg hair,
      respectively. This method could be applied to the analysis of an abuser's hair
      sample.

PMID- 9613939
TI  - Simple high-performance liquid chromatography method for the simultaneous
      determination of serum caffeine and paraxanthine following rapid sample
      preparation.
AB  - A simple reversed-phase high-performance liquid chromatography (HPLC) method for
      the simultaneous determination of caffeine and paraxanthine in human serum is
      described. Serum proteins are precipitated with perchloric acid and the resulting
      supernatant neutralized for direct injection onto an HPLC column. The method uses
      a phosphate-methanol mobile phase (85:15, v/v) at pH 4.9 with a flow-rate of 1.75
      ml/min and quantitation is by UV absorbance at 274 nm. Elution times are
      approximately 18 min for caffeine and 8 min for paraxanthine. Theobromine and
      theophylline have elution times of 5.4 and 9.4 min and do not interfere in the
      assay. The intra-assay and between-assay means for precision and accuracy for
      both drugs are: 4.5% C.V. and 3.3% deviation. The sensitivity of the method is 50
      ng/ml for each drug.

PMID- 9613940
TI  - Liquid chromatography of guanidino compounds using a porous graphite carbon
      column and application to their analysis in serum.
AB  - The retention mechanism of guanidino compounds on a porous graphitic carbon
      seemed to be mainly hydrophobic interaction, according to the retention factors
      in buffer solutions and the results of an analysis by computational chemical
      calculation using molecular mechanics (MM2). The baseline separation of ten
      guanidino compounds was achieved by the addition of a hydrophobic counterion. The
      retention mechanism may be dynamic ion-exchange. The stable system was applied to
      the analysis of guanidino compounds in serum from nephritic patients. The
      effluent was monitored by a post-column labeling detection method using
      ninhydrin. The detection limit of guanidino compounds was a few picomoles;
      however, that of creatinine was one hundredth of those of the other compounds.
      The reproducibilities of the peak height and area of the ten guanidino compounds
      using gradient elution were quite high, and the standard deviations were within a
      few percent (n=5), except for creatinine. The recovery of the compounds from
      serum was more than 90% (n=5). The reproducibility of retention times was within
      1% (n=5).

PMID- 9613941
TI  - Endotoxin removal with poly(ethyleneimine)-immobilized adsorbers: Sepharose 4B
      versus flat sheet and hollow fibre membranes.
AB  - Poly(ethyleneimine) was immobilized on poly(vinyl alcohol)-coated nylon flat
      sheet membranes, poly(vinyl alcohol) and poly(ethylenevinyl alcohol) hollow fibre
      membranes as well as Sepharose 4B. The resulting poly(ethyleneimine)-immobilized
      adsorbers were used for removal of E. coli derived endotoxin from buffers and
      bovine serum albumin solutions. The efficiency of poly(ethyleneimine) proved to
      be constant over a wide pH range, including phosphate buffered saline. The
      performance depended upon the matrix type employed: endotoxin clearance factors
      varied from 100 to 120,000 in protein-free solutions and 40 to 33,000 in
      solutions of bovine serum albumin using 6000 EU/ml as feed concentration. The
      best adsorber was the flat sheet membrane-immobilized poly(ethyleneimine),
      followed by the hollow fibre-immobilized poly(ethyleneimine) and
      poly(ethyleneimine)-Sepharose. The factors influencing endotoxin clearance were
      the mass transport (convective systems were superior to the diffusive system),
      the chemical composition and the surface structure of the underlying matrix.

PMID- 9613942
TI  - Avidin-biotin immobilization of unilamellar liposomes in gel beads for
      chromatographic analysis of drug-membrane partitioning.
AB  - To construct a homogeneous lipid membrane chromatographic phase, biotinylated
      unilamellar liposomes of small and large sizes (SUVs and LUVs, respectively) were
      immobilized in avidin- or streptavidin-derived gel beads in amounts up to 55
      micromol phospholipid/ml gel bed at yields above 50%. The immobilized liposomes
      exhibited excellent stability due to avidin-biotin multiple-site binding. The
      trapped volume and size distribution of the immobilized liposomes (0.33-0.42
      microl/micromol lipid and 20-30 nm diameter for SUVs, 1.7-1.9 microl/micromol
      lipid and 80-120 nm for LUVs) indicated the unilamellarity and integrity of the
      immobilized liposomes. Partitioning of 15 pharmaceutical drugs into the bilayers
      of LUVs immobilized in different gel matrices correlated very well, as shown by
      chromatographic drug retention analysis. The partitioning of several beta
      blockers into the immobilized LUVs showed a close correlation with their
      partitioning, reported in the literature, into free liposomes. The avidin-biotin
      immobilized unilamellar liposomes can thus be used for chromatographic analysis
      and screening of solute-membrane interactions.

PMID- 9613943
TI  - New mathematical approach for the evaluation of drug binding to human serum
      albumin by high-performance liquid affinity chromatography.
AB  - A novel mathematical approach for investigation of drug-human serum albumin (HSA)
      interactions by means of high-performance liquid affinity chromatography is
      developed. The model is based on the assumption that two types of competitive
      binding sites exist on the HSA molecule. The widely used single-site binding
      equation is extended and a proper mathematical analysis is proposed allowing the
      determination of the major parameters characterizing the multisite binding
      (cobinding) process. The utility of the new approach is proved by competitive
      studies on HSA binding of two model drugs, diazepam and diclofenac.

PMID- 9613944
TI  - Determination of the novel non-steroidal anti-inflammatory drug lornoxicam and
      its main metabolite in plasma and synovial fluid.
AB  - A rapid and sensitive HPLC method for the determination of the non-steroidal anti
      inflammatory drug lornoxicam in plasma samples of humans and laboratory animals
      is described. After addition of the internal standard (tenoxicam) the plasma
      sample is acidified and extracted either by dichloromethane via Extrelut columns
      or by solid-phase extraction using C18 columns. After evaporation of the solvent
      the separation is performed on a C18 column in isocratic mode with a mobile phase
      consisting of 0.1 M phosphate buffer (pH 6.0)-methanol and detection at 372 nm.
      The limit of determination was set to 10 ng/ml using 0.5 ml of sample but can be
      extended down to 2.0 ng/ml plasma. Using solid-phase extraction with C18 columns
      both lornoxicam and its main metabolite 5'-hydroxylornoxicam can be determined
      while extraction via Extrelut was used in studies where only lornoxicam was to be
      determined. This method was used successfully in several thousand samples of
      pharmacokinetic and bioavailability studies in animals and in humans.

PMID- 9613945
TI  - Solid-phase extraction-high-performance liquid chromatography determination of
      verapamil and norverapamil enantiomers in urine.
AB  - A simple, rapid, sensitive and selective method has been developed for the
      stereospecific determination of verapamil and its metabolite, norverapamil in
      urine. For sample preparation we utilized a membrane-based solid-phase extraction
      (SPE) disk consisting of a thin, particle-loaded membrane inserted in a plastic
      syringe-like barrel. The particles, which may be C8 or C18 bonded phase (C8 in
      this work), are embedded within a matrix of PTFE (Teflon) fibrils. Overall
      analyte recoveries were above 85%, even at low concentration of 3.0 ng/ml with
      reproducibilities (C.V. values) below 13.1%. This method of extraction has the
      advantage of speed and considerable reduction in solvent volumes compared to
      conventional SPE and solvent extraction. The separation of all the enantiomers
      was achieved using a single chiral stationary phase column, the cellulose-based
      reversed-phase, Chiralcel OD-R. Analyte concentrations of less than 3.0 ng/ml
      could be quantitated with C.V. values below 14%. Calibration curves were linear
      in the range 2.5-300 ng/ml. Intra-day and inter-day reproducibilities were 10.5
      14.2% at 3 ng/ml, 4.8-9.3% at 138.5 ng/ml and 7.8-10.1% at 280 ng/ml level,
      respectively, for all the enantiomers.

PMID- 9613946
TI  - Rapid and simple micromethod for the quantification of fluindione in human plasma
      using high-performance liquid chromatography.
AB  - A new high-performance liquid chromatographic (HPLC) assay without any extraction
      procedure was developed for the quantification of fluindione in plasma using a
      100-microl sample volume and coumarin as the internal standard. A
      deproteinization procedure was coupled with a reversed-phase HPLC separation
      using a 250x4.6 mm I.D. C18 column and a UV detector set at 280 nm. Peak height
      ratios were linear over the range 0.05 to 10 microg/ml (correlation coefficient
      >0.998). The method was found to be highly reproducible, as indicated by the low
      value obtained for the coefficient of variation: C.V. < or = 6.1% (n = 10). The
      limit of quantification, estimated under the described conditions at a signal-to
      noise ratio of three and with a C.V. lower than 20% for precision and accuracy,
      was 0.025 microg/ml. The total turnaround time was 25 min. After storage of blood
      samples at concentrations of 0.1, 0.5 and 2.5 microg/ml at room temperature and
      exposition to light for 120 h, no degradation of fluindione occurred. This
      micromethod is simple (no extraction step), fast and currently is being used for
      drug monitoring.

PMID- 9613947
TI  - Determination of fluoxetine and its metabolite norfluoxetine in serum and brain
      areas using high-performance liquid chromatography with ultraviolet detection.
AB  - A high-performance liquid chromatography (HPLC) method using only 0.1 ml of serum
      or homogenate from brain areas has been developed for the determination of
      fluoxetine (FLU) and its metabolite, norfluoxetine (N-FLU), with ultraviolet
      detection at 227 nm. The small volume of sample required in this method allows
      studies in small animals, such as mouse. The method provides recoveries of up to
      90% for both compounds. Acceptable coefficients of variation were found for both
      within-run and day-to-day assays. The limit of detection was 5.0 ng/ml. No
      interferences were found with tricyclic antidepressant drugs and benzodiazepines,
      which allows this method to be used in clinical studies, Pharmacokinetic
      parameters for the two compounds are reported in mouse serum, frontal cortex and
      caudate nucleus. We also report the values of FLU and N-FLU in serum from humans
      who were treated once daily with 20 mg of FLU, obtained after 1, 14 and 28 days
      of treatment.

PMID- 9613948
TI  - Determination of methylparaben, propylparaben and chlorpromazine in
      chlorpromazine hydrochloride oral solution by high-performance liquid
      chromatography.
AB  - A reversed-phase high-performance liquid chromatographic assay method was
      developed and validated for the simultaneous determination of methylparaben and
      propylparaben preservatives and chlorpromazine hydrochloride active component in
      a liquid oral pharmaceutical formulation. The method separated the analytes as
      well as some degradants and other components, providing good resolution and
      moderate tailing. The performance of various C18 columns was compared. There were
      significant differences in selectivity and only a few phases showed acceptable
      tailing without the addition of triethylamine modifier in the mobile phase.

PMID- 9613949
TI  - Interlaboratory study of the analysis of benzylpenicillin by liquid
      chromatography.
AB  - A liquid chromatography method for analysis of benzylpenicillin was examined in a
      collaborative study involving seven laboratories. The method comprised an
      isocratic part, which is used in the assay. The isocratic part corresponds to the
      assay method for benzylpenicillin used by a manufacturer. When the isocratic part
      is combined with gradient elution, the method is suitable for purity control.
      Five samples of benzylpenicillin (sodium and potassium salts) were analysed. The
      main component and the impurities were determined. An analysis of variance proved
      the absence of consistent laboratory bias. The laboratory-sample interaction was
      not significant. Estimates for the repeatability and reproducibility of the
      method, expressed as standard deviations (S.D.) of the result of the
      determination of benzylpenicillin, were calculated to be 0.71 and 0.80,
      respectively.

PMID- 9613950
TI  - Comparison of (+)-catechin determination in human plasma by high-performance
      liquid chromatography with two types of detection: fluorescence and ultraviolet.
AB  - In this study we developed a high-performance liquid chromatography (HPLC) method
      for the determination of (+)-catechin in human plasma, using both fluorescence
      and UV detection. Sample preparation involved precipitation of plasma proteins
      using acetonitrile, followed by direct injection into the HPLC system using both
      types of detection. Validation of accuracy and precision were satisfactory for
      both within- and between-batch assays. For fluorescence detection, coefficients
      of variation were less than 6.47% and mean relative errors were within +/-4.8%.
      The average recovery was 85.31%. The limit of detection and quantification were 5
      ng/ml and 40 ng/ml, respectively. Ultraviolet detection was also used but
      appeared less sensitive and selective than fluorescence detection. This new
      method provides a simple, accurate, precise and specific method for the
      determination for (+)-catechin in plasma.

PMID- 9613951
TI  - Simple high-performance liquid chromatographic determination of the protease
      inhibitor indinavir in human plasma.
AB  - Indinavir is a member of a class of protease inhibitors that actively prevent the
      acquired immunodeficiency syndrome virion from maturing. A high-performance
      liquid chromatographic (HPLC) assay was developed and validated for the
      determination of indinavir in human plasma. Indinavir and the internal standard
      were isolated from the plasma by ether extraction. The residue after evaporation
      of ether was reconstituted with buffer and injected onto a C4 reversed-phase
      column eluted isocratically with a mobile phase consisting of 35:65 (v/v) of
      acetonitrile and buffer. A wavelength of 210 nm was found to be optimum for
      detection. The calibration range of this assay was from 10 to 5000 ng/ml and
      coefficients of variation for the assay ranged from 4.6% to 11.0% for three
      different drug concentrations and the limit of quantitation was 10 ng/ml. During
      the validation, short-term stability of the drug in plasma, stability during heat
      deactivation and on repeated freezing and thawing of plasma was evaluated. The
      overall recovery of indinavir by the ether extraction method was 91.4%. This HPLC
      assay was found to be a simple and reproducible method for monitoring indinavir
      levels in human plasma obtained during clinical trials of the drug.

PMID- 9613952
TI  - Quantitation of a 36-amino-acid peptide inhibitor of HIV-1 membrane fusion in
      animal and human plasma using high-performance liquid chromatography and
      fluorescence detection.
AB  - Selective extraction of a 36-amino-acid peptide (DP-178, T20, pentafuside) from
      the protein matrices of animal and human plasma was achieved using acetonitrile
      containing 1% trifluoroacetic acid and 1% n-nonyl-beta-D-glucopyranoside. The
      peptide concentration of the extract was measured using reversed-phase high
      performance liquid chromatography (RP-HPLC) and fluorescence detection. The
      eluent was excited at 280 nm and the intrinsic fluorescence signal was collected
      at 350 nm. Recovery of T20 from the plasma matrices was 75% (mouse), 60% (rat),
      50% (cynomolgus monkey), and 55% (human) based on parallel-processed aqueous T20
      standard solutions. The fluorescence peak area vs. concentration of T20 was
      linear in the range 4-160 ng/ml based on the final solute concentration in the
      HPLC vial, corresponding to original plasma concentrations of 100-4000 ng/ml.
      Experiments with truncated analogs of T20 demonstrate that this assay offers the
      advantage of detecting metabolites attributable to bio-transformation degradation
      processes differing by as little as one amino acid from the original peptide.

PMID- 9613953
TI  - Simultaneous determination of epirubicin, doxorubicin and their principal
      metabolites in human plasma by high-performance liquid chromatography and
      electrochemical detection.
AB  - A high-performance liquid chromatographic method with electrochemical detection
      has been developed for the simultaneous determination of epirubicin, 13-S
      dihydroepirubicin, doxorubicin and 13-S-dihydrodoxorubicin in human plasma. An
      aliquot of 200 microl plasma, spiked with internal standard, was extracted by
      solid-phase extraction using polymeric adsorbent columns. Chromatography was
      performed using a C18 reversed-phase column with a mobile phase consisting of
      water-acetonitrile (71:29, v/v) containing 0.05 M Na2HPO4 and 0.05% v/v
      triethylamine adjusted to pH 4.6 with citric acid. Linearity of the method was
      obtained in the concentration range of 1-500 ng/ml for all the analytes.
      Analytical recoveries of the analytes ranged from 89 to 93%. The assay can be
      used for the simultaneous determination of the four analytes, or for epirubicin
      and its metabolite or doxorubicin and its metabolite, using the other parent drug
      as an internal standard. The method was applied to analyze human plasma samples
      from patients treated with epirubicin using doxorubicin as an internal standard.

PMID- 9613954
TI  - High-performance liquid chromatographic quantitation of total and lactone
      20(S)camptothecin in patients receiving oral 20(S)camptothecin.
AB  - We have developed a sensitive high-performance liquid chromatography (HPLC) assay
      to quantitate total and lactone forms of 20(S)camptothecin (CPT) in human plasma.
      Lactone and total CPT were extracted using solid-phase extraction and liquid
      liquid extraction, respectively. The extracted lactone samples could be stored
      without immediate HPLC analysis. The two forms of CPT were quantitated by
      reversed-phase HPLC with fluorescence detection. The extraction efficiencies were
      about 100% and 92% for the total and lactone forms, respectively. The lower limit
      of quantitation was 5.74 nM for the two forms. The method was reproducible with a
      mean interday and intraday variability of 6% for total CPT and 4% and 6%.
      respectively, for lactone CPT. The assay could effectively quantitate lactone and
      total CPT in patients receiving single dose and multiple doses of oral CPT.

PMID- 9613955
TI  - Determination of the enantiomers of chlorpheniramine and its main monodesmethyl
      metabolite in urine using achiral-chiral liquid chromatography.
AB  - The enantiomers of chlorpheniramine and its monodesmethyl metabolite were
      determined separately in urine by using a coupled achiral-chiral chromatographic
      system. The two enantiomers of the studied compound and the internal standard
      were separated from the biological matrix on a cyanopropyl column and reinjected
      into a chiral amylose AD column where the two enantiomers were separated and
      quantified by UV detection. The method was validated for chlorpheniramine and for
      the metabolite within the range 0-1000 ng/ml. It was also applied in a pilot
      pharmacokinetic study to samples from a volunteer given 8 mg of racemic
      chlorpheniramine by mouth.

PMID- 9613956
TI  - High-performance liquid chromatographic determination of the insulin sensitizing
      agent DRF-2189 in rat plasma.
AB  - A high-performance liquid chromatographic method for the determination of DRF
      2189, using troglitazone as internal standard, is described. A dichloromethane
      ethyl acetate solvent mixture (6:4, v/v) was used as the extraction solvent. A
      Kromasil C18 column with a mobile phase consisting of 0.05 M phosphate buffer
      acetonitrile-methanol (22.5:37.5:40) (pH 5.0) was used at a flow-rate of 1.0
      ml/min. The eluate was monitored by using fluorescence detection with excitation
      and emission wavelengths at 292 nm and 325 nm, respectively. Ratio of peak area
      of analyte to internal standard was used for quantification of plasma samples.
      Using this method, the absolute recovery of DRF-2189 from rat plasma was >95% and
      the limit of quantitation was 50 ng/ml. The intra-day relative standard deviation
      (R.S.D.) ranged from 1.74 to 7.24% at 1 microg/ml and 1.86 to 3.83% at 10
      microg/ml. The inter-day R.S.D.s were 8.34 and 4.91% at 1 and 10 microg/ml,
      respectively. The method was applied to measure plasma concentrations of DRF-2189
      in pharmacokinetic studies in Wistar rats.

PMID- 9613957
TI  - Development of a capillary electrophoretic separation of an N-(substituted)
      glycine-peptoid combinatorial mixture.
AB  - Capillary electrophoresis was used for the separation of a combinatorially
      synthesized N-(substituted)-glycine (NSG) peptoid mixture. This mixture consisted
      of 24 trimeric compounds sharing a common backbone structure but differing in the
      side chain attached at the N-terminal residue. Standards of the individual
      components were unavailable so that development of the separation was based on
      the mixture. A variety of buffer additives were investigated to enhance the CE
      resolution of this diverse mixture. Ion-pairing agents, cyclodextrins and organic
      modifiers were all evaluated as buffer additives. The best separations were
      achieved using a combination of buffer additives, each serving a different
      purpose in the separation. Heptane sulphonic acid (HSA) was used to reduce
      hydrophobic intramolecular interactions. Methyl-beta-cyclodextrin was used to
      provide host-guest interactions in order to resolve the very hydrophobic
      components of the NSG-peptoid mixture. The optimized run buffer consisted of 250
      mM sodium phosphate buffer, pH 2.0, with 25 mM HSA and 40 mg/ml BCD and resulted
      in the resolution of 21 peaks for the 24 peptoids in the combinatorial mixture.

PMID- 9613958
TI  - Monoclonal antibody production with on-line harvesting and process monitoring.
AB  - A semi-automated system has been designed for on-line harvesting and monitoring
      of monoclonal antibody (mAb) production. [The antibody was directed against the
      peptide AGPAGTGKTTKDL.] Analytical and purification units were interfaced to the
      fermenter via a hollow fiber cartridge in which fermentation broth was
      continuously circulated through the lumen of the hollow fiber system. Permeate
      from the hollow fiber cartridge was pumped through either an analytical sampling
      loop or a preparative Protein G column where antibody species were captured.
      Switching between monitoring and harvesting was achieved by two 3-way toggle
      valves. Samples from the analytical sampling loop were transported to an
      analytical Protein G chromatography column for quantitation of all immunoglobulin
      G species in the fermenter. Data acquisition and processing was performed by the
      data system of the liquid chromatograph. All valves in the system except the two
      toggle valves were controlled by the liquid chromatograph. Antibody biosynthesis
      was monitored for the first 60 h of fermentation. Harvesting was initiated when
      mAb accumulated in the fermenter. Complete harvesting took approximately 90 h.

PMID- 9613959
TI  - Sodium dodecylsulfate polyacrylamide gel electrophoresis of recombinant hepatitis
      B surface antigen particles.
AB  - To investigate the factors leading to broadening of the recombinant hepatitis B
      surface antigen (HBsAg) peak in size-exclusion chromatography, the HBsAg
      particles eluting in different regions of the peak were subjected here to
      electrophoretic analysis. In nonreduced samples, the 24-kD band corresponding to
      the S monomer was detected when excessively large amounts of HBsAg were loaded
      onto the gel. Hence, some monomers are not disulfide-crosslinked in assembled
      particles. On the other hand, the results of alkylation experiments indicated the
      presence of free sulfhydryl group(s) in a little portion of freshly-purified
      HBsAg which was retarded on the size-exclusion chromatographic column and had
      significant antigenicity. This fraction of HBsAg was shown to be oligomeric and
      capable of spontaneous assembly into higher-order structures during aging.

PMID- 9613960
TI  - Quantitative capillary electrophoresis-ion-trap mass spectrometry determination
      of methylphenidate in human urine.
AB  - A quantitative capillary electrophoresis-mass spectrometry method has been
      demonstrated for the determination of methylphenidate in human urine over a
      dynamic range of 640. The samples were prepared by liquid-liquid extraction using
      4 ml of human urine. The extracts were analyzed using a Finnigan LCQ ion-trap
      mass spectrometer in a two-event, positive-ion full-scan MS and tandem MS
      selected reaction monitoring mode. The lower level of quantitation was determined
      to be 1.5 ng/ml methylphenidate in human urine. The intra-assay precision had a
      relative standard deviation less than 6.8%. The intra-assay accuracy was less
      than +/-14.7% bias from the nominal concentration for the full-scan MS analysis,
      and less than +/-26.5% bias for the tandem MS analysis. Six incurred human urine
      samples containing methylphenidate were analyzed and a simple pharmacokinetic
      curve is presented.

PMID- 9613961
TI  - Enantiomeric separation of tramadol hydrochloride and its metabolites by
      cyclodextrin-mediated capillary zone electrophoresis.
AB  - The enantiomeric separation of tramadol hydrochloride and its major metabolites,
      O-demethyltramadol (M1) and N-demethyltramadol (M2) was studied using
      cyclodextrin (CD)-mediated capillary zone electrophoresis (CZE). Influence of the
      choice of type and concentration of CD, capillary temperature, length of
      capillaries, buffer pH and the addition of polymer modifier on the chiral
      separation of tramadol and its metabolites was evaluated. It was found that the
      drug and the metabolites can be baseline-separated simultaneously by using 50 mM
      phosphate buffer (pH 2.5) containing 75 mM methyl-beta-CD, 220 mM urea and 0.05%
      (w/v) hydroxypropylmethyl cellulose.

PMID- 9613963
TI  - Simultaneous detection of reduced and oxidized glutathione in tissues and
      mitochondria by capillary electrophoresis.
AB  - We have developed a rapid and precise method for glutathione quantitation by
      capillary electrophoresis, that allows a low amount of both redox forms to be
      measured. Small fragments of rat heart or liver tissues (20 mg wet weight) and
      the corresponding mitochondria (1 mg protein) were homogenized in 1% perchloric
      acid and the acid-soluble phase ultrafiltered by centrifugation with a
      microconcentrator (Mr cut-off 3000 Da). The analysis was performed at a constant
      temperature (28 degrees C) using a Beckman P/ACE System 2100, equipped with a UV
      absorbance detector set to 200 nm. The limit of quantitation in heart tissue was
      1.8 microM for GSH and 1.2 microM for GSSG. Myocardial concentrations of GSH and
      GSSG were 8.1 +/- 2.6 and 0.45 +/- 0.15 (nmol/mg protein +/- S.D.), respectively.
      The ratio of GSH to GSSG was 17.8 +/- 1.3 for heart tissue, whereas it was much
      higher (>100) in the mitochondria. An oxidative stress decreased the myocardial
      tissue GSH/GSSG ratio, indicating that the CE analysis of both glutathione forms
      is also a useful method to study biological redox modification.

PMID- 9613962
TI  - Ion-exchange column chromatographic method for assaying purine metabolic pathway
      enzymes.
AB  - High energy phosphate levels fall rapidly during cardiac ischemia and recover
      slowly (more than one week) during reperfusion. The slow recovery of ATP may
      reflect a lack of purine metabolic precursors and/or increased activity of purine
      catabolic enzymes such as 5'-nucleotidase (5'-NT, EC 3.1.3.5) and adenosine
      deaminase (ADA, EC 3.5.4.4). The activity of enzymes involved in both the
      catabolism of ATP precursors (5-NT and ADA) and the restoration of ATP from slow
      synthetic pathways [adenosine kinase (AK, EC 2.7.1.20), adenine phosphoribosyl
      transferase (APRT, EC 2.4.2.7) and hypoxanthine phosphoribosyl transferase (HPRT,
      EC 2.4.2.8)] may directly affect the rate of ATP recovery. Strategies to enhance
      recovery will depend on the relative activity of these enzymes following
      ischemia. Their activity in different species and their response to ischemia are
      not well characterized. Hence, rapid assay methods for these enzymes would
      facilitate detailed time course studies of their activities in postischemic
      myocardium. We modified a single ion-exchange column chromatographic method using
      DEAE-Sephadex to determine the products of incubation of 5'-NT, AK, APRT and HPRT
      with their respective substrates. The uniformity of the final product measurement
      procedure for all assays permits the activities of the four enzymes to be rapidly
      determined in a single tissue sample and facilitates the study of a large number
      of samples. This technique should also be useful for enzymes of the pyrimidine
      metabolic pathway.

PMID- 9613964
TI  - Sensitive method for measuring tissue alpha-tocopherol and alpha
      tocopheryloxybutyric acid by high-performance liquid chromatography with
      fluorometric detection.
AB  - The nonhydrolysable tocopherol ether analog, d-alpha-tocopheryloxybutyric acid
      (TSE), and its tocopherol ester counterpart, d-alpha-tocopheryl hemisuccinate
      (TS), have been shown to possess anti-tumor activity. In the present study, a
      sensitive high-performance liquid chromatography (HPLC) method using fluorometric
      detection is described for the simultaneous determination of TSE and alpha-T in
      biological specimens. Maximal sensitivity for the measurement of TSE and alpha-T
      was observed with the wavelengths, 210 nm excitation and 300 nm emission. Using
      an internal standard (I.S.) method, the amount of these tocopherol compounds was
      determined in standards, liver homogenates isolated from rats administered TSE
      tris salt or vehicle (saline) and in HL-60 human leukaemia cells incubated with
      TSE-tris salt or saline. Treatment with TSE resulted in the significant
      accumulation of TSE, but not alpha-T, in the liver and HL-60 cells.

PMID- 9613965
TI  - Rapid solid-phase extraction method for automated gas chromatographic-mass
      spectrometric determination of nicotine in plasma.
AB  - The aim of this study was to develop a simple, rapid and sensitive assay of
      nicotine in plasma for automated gas chromatographic-mass spectrometric analysis.
      Biological samples were extracted using pre-packed Extrelut-1 columns with 5 ml
      of ethyl acetate. Quantitative analysis was done using deuterium-labelled
      nicotine as internal standard. The limit of quantitation was 0.5 ng in 1-ml
      plasma samples. Precision was ranging from 13.3% to 1.64% (R.S.D.) depending on
      the concentration, while the deviation was 4.16%. This method has been used for
      determination of nicotine bioavailability from new, low-dosage, nicotine chewing
      gum strips.

PMID- 9613966
TI  - Determination of nicotine, cotinine and caffeine in meconium using high
      performance liquid chromatography.
AB  - A high-performance liquid chromatographic method with diode-array detection for
      the determination of nicotine and its metabolites, cotinine and caffeine, in
      meconium is described. This method is suitable to assess foetus exposure to
      tobacco smoke. The analytes were extracted by solid-phase extraction before
      chromatography. From among 30 meconium samples 11 were positive for cotinine (20
      86 ng/g) and 27 for caffeine (10-45 ng/g). No nicotine was present in the samples
      because of its rapid metabolism into cotinine.

PMID- 9613967
TI  - Determination of aspirin and salicylic acid in transdermal perfusates.
AB  - A high-performance liquid chromatographic (HPLC) method has been developed for
      the simultaneous determination of aspirin and salicylic acid in transdermal
      perfusates. The compounds were separated on a C8 Nucleosil column (5 microm,
      250x4.6 mm) using a mobile phase containing a mixture of water-acetonitrile
      orthophosphoric acid (650:350:2, v/v/v) and a flow-rate of 1 ml/min. The
      transdermal samples were in phosphate-buffered saline (PBS) and could be injected
      directly onto the HPLC system. The method was reproducible with inter-day R.S.D.
      values of no greater than 3.46 and 2.60% for aspirin and salicylic acid,
      respectively. The method was linear over the concentration range 0.2-5.0
      microg/ml and had a limit of detection of 0.05 microg/ml for both compounds. For
      certain samples, it was necessary to ensure that no transmembrane leakage of the
      aspirin prodrugs had occurred. In these cases, a gradient was introduced by
      increasing the acetonitrile content of the mobile phase after the salicylic acid
      had eluted. The method has been applied to the determination of aspirin and
      salicylic acid in PBS following in vitro application of the compounds to mouse
      skin samples.

PMID- 9613968
TI  - Determination of SK&F 108566 (Teveten) in human plasma by reversed-phase high
      performance liquid chromatography.
AB  - A sensitive, selective and rugged analytical method was developed for the
      determination of SK&F 108566 (eprosartan, Teveten) in human plasma. The new
      method employs a simple solid-phase extraction procedure to isolate the drug and
      its internal standard (SB-200062) from plasma samples. The assay is based on
      analysis by reversed-phase high-performance liquid chromatography with
      ultraviolet absorbance detection. The dynamic range of the assay is from 10.0 to
      5000 ng/ml, based on 0.5-ml aliquots of plasma. No interference from the
      endogenous components of plasma, the anticoagulant, or sample collection devices
      have been noted. The assay has been fully validated. The mean within-run
      precision (6.5%), between-run precision (4.0%), accuracy (106%) and recovery
      (71.8%) of the method were considered acceptable. Additionally, SK&F 108566 was
      found to be stable in plasma under the storage and sample preparation conditions
      used. This assay has been successfully employed to provide pharmacokinetic data
      from clinical trials.

PMID- 9613969
TI  - Determination of dimethindene in human tears by high-performance liquid
      chromatography.
AB  - A high-performance liquid chromatographic method is described for the
      determination of dimethindene in human tears. The tear samples were diluted in a
      0.01 M hydrochloric acid-n-propanol mixture to prevent the irreversible
      adsorption of dimethindene. The diluted samples were directly injected into the
      chromatographic system to avoid sample pretreatment. The validation data
      demonstrate that the method is specific, precise and accurate within the
      calibration range of 12 to 1000 ng/ml dimethindene free base.

PMID- 9613970
TI  - Simple, rapid and sensitive determination of protionamide in human serum by high
      performance liquid chromatography.
AB  - A simple high-performance liquid chromatography method has been developed that
      allows the sensitive determination of protionamide (2-n-propyl-pyridine-4
      carboxylic acid thioamide, PTH) in human serum. After pretreatment of the serum
      with trichloroacetic acid (TCA) and centrifugation the supernatants were
      neutralized using NaHCO3. PTH was separated on a Kromasil 100 C4 column
      (acetonitrile-sodium tetraborate buffer pH 8-dibutylamine) and determined
      photometrically at 291 nm. The lower limit of quantification for 300 microl serum
      precipitated with 60 microl TCA and injection of 50 microl was 27 microg/l and
      linearity was observed up to 15 mg/l.

PMID- 9613971
TI  - Assay for etoposide in human serum using solid-phase extraction and high
      performance liquid chromatography with fluorescence detection.
AB  - An HPLC assay for etoposide in human serum was developed. Serum, spiked with
      podophyllotoxin (internal standard), was treated with sodium dodecyl sulphate
      prior to solid phase extraction. Analysis was performed on a 300x3.9 mm Bondclone
      10 C18 column coupled with a fluorometric detector (lambda(ex) 230 nm, lambda(em)
      330 nm). The retention times for etoposide and podophyllotoxin were 14 and 28 min
      respectively. The range of assay was 0.5 to 20 microg/ml with a detection limit
      of 0.2 microg/ml. This assay is suitable for use in clinical studies with
      etoposide.

PMID- 9613972
TI  - Assessment of microsomal tolbutamide hydroxylation by a simple thin-layer
      chromatography radioactivity assay.
AB  - A radio thin-layer chromatographic method is described for in vitro measurement
      of tolbutamide methylhydroxylation as an alternative to the commonly used HPLC
      assay. After the incubation experiments of [14C]tolbutamide with human liver
      microsomes, the supernatants were directly spotted onto standard silica gel TLC
      plates and developed in a horizontal chamber using a solvent system consisting of
      toluene-acetone-formic acid (60:39:1, v/v). Dried TLC plates were exposed to a
      phosphor imager plate and quantificated by use of a phosphor imager. Reaction
      rates were calculated from the ratio of labelled metabolite to the total
      radioactivity. The correlation coefficient between HPLC and the TLC method was
      0.978 (n=14). The described method provides a valuable tool for the determination
      of tolbutamide hydroxylation activity in human liver microsomes.

PMID- 9613973
TI  - New directions in understanding interleukin-5 gene expression.
AB  - Specific regulation of the interleukin-5 (IL-5) gene is implied by the unique
      control of eosinophilia which is regulated by IL-5. In studies of IL-5 gene
      expression, the only control elements identified for the IL-5 gene have been
      transcriptional elements in the 5' untranslated region (UTR). Significant
      differences exist in the arrangement of the murine and human IL-5 promoters,
      which is surprising considering the tight regulation of the gene. Novel
      palindromic regulatory elements involved in transcriptional regulation have been
      found in the 5' UTR and new results show the presence of transcriptional elements
      in the 3' UTR. Post-transcriptional control mechanisms in both the 5' and 3' UTRs
      have also been described.

PMID- 9613974
TI  - BCL-X and the apoptotic machinery of lymphoma cells.
AB  - The BCL-X gene belongs to the family of BCL-2 homologues and plays an important
      role in the regulation of programmed cell death (PCD) in normal lymphoid tissues.
      BCL-X is transcribed into 2 mRNAs through alternative splicing. The protein
      product of the larger BCL-X mRNA (BCL-XL) functions as a PCD repressor. The
      second mRNA species, BCL-XS, encodes a protein capable of accelerating cell
      death. BCL-XL is a potential contributor to the pathogenesis of malignant
      lymphomas because the BCL-XL isoform is predominantly expressed by the neoplastic
      cells in the majority of lymphoma cases. This review is focused on the possible
      influence of BCL-X and other PCD regulatory agents on lymphomagenesis.

PMID- 9613975
TI  - The JAK-STAT pathway: signal transduction involved in proliferation,
      differentiation and transformation.
AB  - STAT proteins become activated upon tyrosine and serine phosphorylation, are
      subsequently translocated from the cytosol to the nucleus where they exert DNA
      binding activity. Several STAT binding consensus motifs have been identified in
      the promoters of distinct genes. These consensus elements mediate STAT
      recruitment and influence the kind of STAT proteins that are bound at a specific
      promoter site. Recent structure function analyses have revealed conserved amino
      terminal sequences to be crucial for phosphatase dependent deactivation of the
      STAT proteins. To date an increasing amount of data is available concerning the
      on- and off-regulation of STAT activity. Considerable convergence as well as
      crosstalk has been shown between the JAK-STAT pathway and the MAPK, RAS, PI3K,
      PKC, and PKA involving pathways. Moreover, the nature of the genes that are
      regulated by STAT proteins as well as the cell functions that result from STAT
      activation are of great current interest. Understanding the critical functional
      role of STAT mediated signalling events as well as their regulation by
      interfering pathways provides new insights into the mechanisms involved in
      malignant cell proliferation.

PMID- 9613976
TI  - Prognostic value of P-glycoprotein and leukocyte differentiation antigens in
      chronic myeloid leukemia.
AB  - P-glycoprotein (Pgp) mediated multidrug resistance is often the cause of therapy
      failure in some tumors. Pgp expression was shown to have prognostic value in
      several hematological malignancies, especially in acute myeloblastic leukemia
      (AML) and acute lymphoblastic leukemia (ALL). In chronic myeloid leukemia (CML)
      Pgp is expressed by peripheral blood (PB) cells more often in the terminal
      disease stages (20-50% of patients have Pgp+ phenotype). Sequential studies show
      that Pgp+ cells often disappear from the PB during the course of therapy.
      Nevertheless Pgp expression has some prognostic value in blast crisis (BC)
      predicting shorter BC, while CD13 has the same predictive value in BC. 10% of
      patients formed a distinct group with large numbers of Pgp+CD34+ blasts in the PB
      and also had shorter BC. Cases with inactive Pgp were found in chronic and
      accelerated phases of CML but not in BC.

PMID- 9613977
TI  - The Fas antigen and Fas-mediated apoptosis in B-cell differentiation.
AB  - In the B-cell lineage, Fas, a type 1 membrane protein belonging to the tumor
      necrosis factor receptor (TNF) family, is expressed on B-cells at a restricted
      developmental stage and on activated B-cells, but not on naive mature B-cells.
      Apoptosis mediated by Fas-Fas ligand interactions may be involved in the
      peripheral elimination of autoreactive B-cells and in the regulation of the
      immune response through deletion of B-cells activated by foreign antigens, as for
      the T-cell lineage. Fas-mediated apoptosis associated with B-cell activation is
      affected by costimulation through other accessory signaling molecules like CD40,
      whose ligands are on T-cells.

PMID- 9613978
TI  - Hematopoietic growth factors for the treatment of myelodysplastic syndromes.
AB  - Administration of recombinant human granulocyte colony-stimulating factor (rhG
      CSF), rh granulocyte-macrophage colony-stimulating factor (rhGM-CSF) or rh
      interleukin-3 (rhIL-3) effectively stimulate and expand marrow myelopoiesis
      resulting in a dose-dependent increment of peripheral blood neutrophils in most
      patients with myelodysplasias (MDS). Clinical outcome with fewer infections have
      been reported in a few studies using rhG-CSF or rhGM-CSF, including a large
      randomized, controlled trial with rhGM-CSF. Clinical effective stimulation of
      megakaryopoiesis and erythropoiesis are however infrequent. Recently, rh
      erythropoietin (rhEpo) has been used to overcome the ineffective erythropoiesis
      in MDS to reduce transfusions needed. However, the efficiency has been low in
      most studies with marked differences in response rates. The most impressive
      clinical results were obtained in patients with milder forms of MDS combined with
      low prestudy endogenous S-Epo levels. The possible synergistic effect of
      combining rhEpo with rhG-CSF or rhGM-CSF has been studied with erythropoietic
      response rates of about 40%. The safety of the cytokine administration seems
      acceptable with no significant stimulation of leukemic myelopoiesis and
      subsequent progression into overt acute myeloid leukemia. In conclusion,
      combinations of hematopoietic growth factors may be of clinical benefit in some
      patients with MDS. However, due to the cost and unpredictable clinical outcome
      there is a need for extended laboratory research to understand the functional
      defects of MDS stem cells and progenitors.

PMID- 9613979
TI  - Collection of more hematopoietic progenitor cells with large volume leukapheresis
      in patients with multiple myeloma.
AB  - Reinfusion of mobilized peripheral blood stem cells (PBSC) after high dose
      chemotherapy accelerates hematopoietic recovery. Because of the relatively low
      content of hematopoietic progenitors in the peripheral blood even after
      mobilization, multiple leukapheresis procedures are necessary to reach the
      required target number of CD34 cells to ensure prompt engraftment post
      transplantation. Our previous studies have shown that the highest proportions of
      hematopoietic progenitors cells (CD34) are collected during the first three days
      of apheresis, whereas peak levels of myeloma cells are observed during subsequent
      days. Therefore, large volume leukapheresis (LVL), defined as processing of
      greater than 3 blood volumes or a total of at least 15 liters, was explored in 23
      myeloma patients, undergoing 91 procedures; 14 patients were mobilized with high
      dose cyclophosphamide (6g/m2) and hematopoietic growth factors and 9 with G-CSF
      only. CD34 yields were measured separately for the first and last two hours of
      collection. We observed no decrease in CD34 cells/kg during the last two hours of
      collection and when the LVL collections were compared to historical matched
      controls, mobilized with the same regimen, the median quantity of CD34
      cells/kg/liter collected remained equivalent during all days of apheresis. When
      compared to G-CSF only, mobilization with high dose cyclophosphamide appeared to
      result in superior hematopoietic stem cell collections. Interestingly, the G-CSF
      group experienced a progressive decrease in platelets during consecutive days of
      LVL, while the opposite was seen in the cyclophosphamide group. LVL procedures
      were not associated with a higher complication rate than standard volume
      apheresis. We conclude that LVL procedures allow collection of more CD34 cell per
      session while not jeopardizing progenitor cell collections during subsequent
      sessions. Since more CD34 cells are collected, fewer days are required to attain
      the optimal target of progenitor cells. This should result in PBSC grafts with
      less tumor contamination.

PMID- 9613980
TI  - Combined therapeutic efficacy of the thymidylate synthase inhibitor ZD1694
      (Tomudex) and the immunotoxin B43(anti-CD19)-PAP in a SCID mouse model of human B
      lineage acute lymphoblastic leukemia.
AB  - The quinazoline antifolate N-(5-[N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6
      ylmethyl)-N- methylamino]-2-thenoyl)-L-glutamic acid (ZD1694; Tomudex) is a
      potent inhibitor of thymidylate synthase and causes cell death through disruption
      of DNA synthesis and repair by blocking the obligatory thymidine nucleotide
      synthesis. B43(anti-CD19)-PAP immunotoxin is a potent inhibitor of protein
      synthesis in CD19+ B-lineage acute lymphoblastic leukemia (ALL) cells and causes
      apoptosis. In this model, 100% of SCID mice challenged with 1 x 10(6) human NALM
      6 B-lineage ALL cells develop overt and invariably fatal leukemia. All of the 22
      control SCID mice treated with phosphate-buffered saline died of disseminated
      human leukemia between 31 and 61 days with a median survival of 41.2 days.
      Treatment with ZD 1694 resulted in improved leukemia-free survival with a median
      survival of 69.2 days (P < 0.001, log-rank test). B43-PAP treatment was more
      effective than ZD1694 (P=0.026) and resulted in 51.0% long-term leukemia-free
      survival with a median survival of 187.5 days (P < 0.0001. log-rank test). The
      combination of ZD1694 and B43-PAP was more effective than either agent alone and
      resulted in 100% long-term leukemia-free survival. To our knowledge, this
      preclinical study is the first to demonstrate the feasibility and therapeutic
      advantage of combining an anti-leukemia immunotoxin with a thymidylate synthase
      inhibitor.

PMID- 9613981
TI  - Sezary syndrome, T-helper 2 cytokines and accessory factor-1 (AF-1).
AB  - Mycosis fungoides and the Sezary Syndrome are characterized by clonal
      accumulation of well differentiated T-helper memory cells in the skin and, in the
      case of the Sezary Syndrome, also in the blood and lymph nodes. Well known
      immunological abnormalities in patients with MF and SS include reduced delayed
      type hypersensitivity, decreased proliferation upon stimulation with mitogens of
      the peripheral blood mononuclear cells, elevated IgE or IgA serum levels and
      eosinophilia. These abnormalities can be explained by the predominance of T
      helper 2 cytokines. Clonal T-lymphocytes purified from the peripheral blood of SS
      patients transcribe mainly IL-10 and IL-5. They can be CD7 positive or negative.
      These clonal T cells express the accessory factor-1 (AF-1) or Interferon gamma
      receptor beta-chain that is essential for Interferon gamma signalling. These
      results imply perspectives for new therapeutical approaches, such as IL-12 or
      chimeric fusion proteins.

PMID- 9613982
TI  - Sea-blue histiocyte syndrome in bone marrow secondary to total parenteral
      nutrition.
AB  - Clinical and hematological abnormalities can occur in patients receiving
      intravenous fat emulsions as part of a long-term parenteral nutrition; they
      consist of hepatosplenomegaly and peripheral blood cytopenia(s). These
      abnormalities lead to bone marrow examination which revealed numerous macrophages
      laden with blue staining pigment granules and separate lipid vacuoles, presenting
      the typical histochemical characteristics of sea-blue histiocytes. Thus, long
      term parenteral nutrition including fat-emulsion sources may represent a further
      condition in addition to the wide variety of disorders which can be associated
      with sea-blue histiocytosis. Moreover, in view of its clinical and morphological
      presentation, this storage pathological state could be compared with the so
      called sea-blue histiocyte syndrome described by Silverstein and colleagues.

PMID- 9613983
TI  - Myelodysplastic syndromes in childhood: is the FAB classification relevant?
      Report of 81 children from a French multicentre study. French Group of Cellular
      Hematology.
AB  - We reviewed the peripheral blood and bone marrow smears of 81 children with
      myelodysplastic syndrome (MDS). The morphological FAB classification was
      applicable in 59 children (72.8%): RAEB and RAEBt were the most frequent, 32
      cases (39.5%). CMML was observed in 15 cases (18.5%) and in 25% of them,
      serological evidence for a recent EBV infection was demonstrated. In 22 cases
      (27.2%), the FAB classification was not convenient. In some of these children,
      dysmyelopoiesis was associated with constitutional disorders. Among these various
      inherited conditions, Down syndrome in which myelodysplasia is the expression of
      an abnormal clonal hematopoiesis, and mitochondrial cytopathies in which MDS is
      the hematological expression of a polyclonal multi-organ disease. The FAB
      classification does not appear to be satisfactory for all the disorders included
      in the group of childhood MDS and should be modified for specific use in
      children.

PMID- 9613984
TI  - Importance of mixed chimerism to predict relapse in persistently BCR/ABL positive
      long survivors after allogeneic bone marrow transplantation for chronic myeloid
      leukemia.
AB  - Determination of hematological chimerism could be helpful in understanding the
      biology of leukemic relapse after allogeneic bone marrow transplant (BMT) for
      chronic myeloid leukemia (CML), because the detection of malignant residual cells
      carrying the bcr/abl message by qualitative RT-PCR is of limited value in
      predicting disease progression for individual patients. We have studied the
      chimerism pattern and the bcr/abl status by Southern-blot in 15 CML patients
      (M/F:6/9) transplanted with unmanipulated BM from HLA identical sibling donors,
      persistently bcr/abl positive by RT-PCR. The median age of the series was 31
      years (18-49) and disease status at BMT was: chronic phase: 11, accelerated
      phase: 3 and blast crisis: 1 patient. Of the 15 patients, 9 are alive and in
      complete remission (CR), 4 have died in CR and 2 are alive but suffered relapse
      at + 19 and +26 months post-BMT. The median follow-up is 81 months (13,7-168).
      Rearrangement of the BCR gene was performed by Southern-blot using P32-labeled
      transprobe-1. PCR analysis of chimerism was assessed using primers for the
      following VNTR loci: D1S80, D1S111, 33.1, APO-B, YNZ-22, lambdag3 and DXS52.
      Seventy-nine samples were analyzed (median per patient 5 (range 2-9)). Thirteen
      patients showed complete chimerism and lacked BCR rearrangement over time by
      Southern-blot. The 2 patients who relapsed showed mixed chimera status from +9
      and +5 months respectively until the end of the study. Persistent BCR
      rearrangement was observed in these 2 patients from +12 and +11 months
      respectively. Our data suggest that mixed chimerism may predict hematologic or
      cytogenetic relapse by several months in those patients who are persistently PCR
      positive post-BMT.

PMID- 9613985
TI  - Suppression of proliferation and phosphorylation of Jak3 and STAT5 in malignant T
      cell lymphoma cells by derivatives of octylamino-undecyl-dimethylxanthine.
AB  - IL-2R signal transduction involves tyrosine phosphorylation of several proteins
      including Jak3 and STAT5. In the present study we examined the effect of two
      octylamino-undecyl-dimethylxanthine (OUDMX) derivatives, designated CT2576 and
      CT5589, on proliferation and protein tyrosine phosphorylation in human malignant
      T-cell lymphoma lines. These T-cell lines (PB-1, 2A, and 2B), obtained from a
      progressive T-cell lymphoma involving skin, are IL-2 independent but have
      constitutively activated IL-2R-associated signal transduction pathway common to
      IL-2 and several other cytokines: IL-4, IL-7, IL-9, and IL-15. CT2576,
      characterized previously on the functional level as an inhibitor of IL-2
      signaling and, on the biochemical level, as an inhibitor of phosphatidic acid
      biosynthesis, suppressed completely growth of the malignant T cell lymphoma
      lines. CT5589 which is a novel analog of the CT2576, displayed a similar,
      although weaker, effect. Furthermore, both CT compounds inhibited constitutive
      tyrosine phosphorylation of two proteins: Jak3 and STAT5 which are key downstream
      elements in the signal transduction pathway activated by IL-2 and the other
      cytokines. The CT compounds inhibited also Jak3 phosphorylation induced by IL-2
      in the IL-2 dependent SZ-4 cells. Inhibition of phosphorylation by CT2576 and
      CT5589 was only partially selective since phosphorylation of several other
      proteins was also affected. Phosphorylation of many others was, however,
      unaffected. These findings demonstrate that the OUDMX derivatives suppress
      proliferation of malignant T lymphocytes. Furthermore, they suggest that this
      suppression may be mediated by inhibition of the IL-2R-associated Jak/STAT
      signaling pathway. A potential role for OUDMX derivatives in therapy of human T
      cell lymphoma should be further explored.

PMID- 9613986
TI  - Chromosome breaks and sister chromatid exchange as predictors of second cancers
      in Hodgkin's disease.
AB  - Hodgkin's disease (HD) survivors face an increased risk of developing second
      cancers. We evaluated baseline cytogenetic biomarkers, sister chromatid exchange
      (SCE) and chromosome breaks [spontaneous (SCB) and bleomycin-induced (BIB)], as
      predictors of second cancer risk in a cohort of 105 adult HD patients. During
      follow-up, seven second cancers occurred. SCBs and BIBs showed no association
      with risk of second primaries. Multivariate Cox regression revealed that high
      levels of SCEs (relative risk (RR)=11.3, p=0.02) and age (RR=1.08, p=0.02)
      predicted second cancer risk. Histology, stage, and treatment were not associated
      with elevated risk. In conclusion, baseline SCE frequencies may be a useful
      biomarker for identifying HD patients at increased risk of developing second
      cancers. These results need to be verified in a larger cohort with a longer
      follow-up time.

PMID- 9613987
TI  - BCL-2 immunohistochemical evaluation in B-cell chronic lymphocytic leukemia and
      hairy cell leukemia before treatment with fludarabine and 2-chloro-deoxy
      adenosine.
AB  - Bcl-2 overexpression has been shown to be associated with several malignancies,
      including B-cell chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphomas
      (NHL), mainly low-grade and follicular in type. It has as yet not been described
      in hairy cell leukemia (HCL). In 30 patients with CLL and 14 with HCL who were
      consecutively selected for treatment with purine analogues (Fludarabine in CLL
      and 2-chloro-deoxy-adenosine in HCL), we evaluated bcl-2 oncoprotein expression
      in leukemic cells on marrow sections that were taken before treatment and stained
      immunohistochemically with a monoclonal antibody (Dakopatts 124 clone), by the
      avidin-biotin-peroxidase method. All samples were found to be bcl-2 positive,
      with a staining intensity that was moderate to strong in CLL and weak to moderate
      in HCL. 83% of CLL and 100% of HCL patients were responsive to purine analogues.
      These findings show that bcl-2 is overexpressed in almost all cases CLL and HCL
      and that bcl-2 overexpression does not predict a poor response to purine
      analogues, which are believed to induce apoptosis.

PMID- 9613988
TI  - Blocking of MHC class I antigens on leukemic B-cells enhances their conjugate
      formation with cytotoxic lymphocytes and their susceptibility to lysis.
AB  - The role of major histocompatibility complex (MHC) class I antigens and adhesion
      molecules (AM) in the resistance of leukemic B-cells to cell-mediated
      cytotoxicity was investigated using cells from eight patients with B-chronic
      lymphocytic leukemia (B-CLL) and six patients with immunocytoma (IC). Both CLL
      and IC cells were completely resistant to natural killer (NK) and lymphokine
      activated killer (LAK) cytotoxicity and no binding to effector cells was
      observed, irrespectively of AM expression. Blocking of MHC class I antigens with
      monoclonal antibodies or their temporary elimination from leukemic B-cell surface
      by acid treatment resulted in a significant (p < 0.005) increase in both
      conjugate formation and susceptibility to lysis, thus suggesting the relevance of
      MHC class I expression on leukemic B-cells for the NK/LAK resistance phenomenon.

PMID- 9613989
TI  - CD45RO expression on peripheral lymphocytes as a prognostic marker for adult T
      cell leukemia.
AB  - Adult T-cell leukemia (ATL) is an aggressive hematological malignancy
      etiologically linked to HTLV-I. The clinical subtype classification, age,
      performance status, serum calcium and LDH levels are major prognostic factors of
      ATL, but these criteria and factors do not always correlate with prognosis. CD45
      is expressed on cells of the hematopoietic system, and plays a pivotal role in
      antigen-stimulated proliferation of T-lymphocytes. CD45RO is a very light weight
      isoform of CD45 expressed on activated T-cells. Recent studies have shown that
      peripheral lymphocytes show two patterns of CD45RO expression in HTLV-I infected
      individuals which appears to correlate with their clinical outcome. The acute
      type ATL patients have pattern A with CD45RO+ lymphocytes with intermediate
      expression (CD45ROint cells), and show a better prognosis than those who do not
      have any CD45ROint cells. Further studies demonstrated that CD45ROint cells were
      not infected with HTLV-I, and as a result we suggest that CD45RO expression be
      considered a marker of host immunity in acute type ATL clinical course, in
      contrast to the levels of WBC or LDH which are regarded as tumor markers and
      indicators of tumor mass.

PMID- 9613990
TI  - Clinical significance of detecting p53 protein in Burkitt lymphoma and B-cell
      acute lymphoblastic leukemia using immunocytochemistry.
AB  - P53 protein expression in malignant cells of five patients with Burkitt lymphoma
      (BL) and from two patients with B-cell acute lymphoblastic leukemia (B-ALL) was
      examined with anti p53 protein monoclonal antibodies PAb1801, PAb240 and p53-D07
      using an immunocytochemical technique. Four of the seven patients were positive.
      The distribution of positive staining within the cell was predominantly in the
      nucleus. The reactivity of PAb240 was weaker than that of the other antibodies.
      In addition, three of the four positive cases showed the same abnormal karyotype;
      translocation (8;14) (q24;q32). All of the four positive cases died due to
      relapse of their primary disease. The three negative cases did not show
      karyotypic abnormalities and are still alive and well. In conclusion, p53
      immunostaining technique may be useful for predicting the clinical outcome of B
      cell malignancy.

PMID- 9613991
TI  - Tuberculosis-associated fatal hemophagocytic syndrome in a patient with lymphoma
      treated with fludarabine.
AB  - A patient with a stage IV high-grade non-Hodgkin's lymphoma who developed a fatal
      hemophagocytic syndrome is presented: When the patient had achieved complete
      remission and receiving fludarabine and chlorambucil/prednisone, she developed
      miliary tuberculosis, the CD4+ T-cell count then being 50/microL; the
      hemophagocytic syndrome ensuing at this point was fatal. Speculations about the
      predisposing factors that could have led to this complication are discussed
      focusing on the severe cellular immunosuppression which developed probably
      related to the use of fludafabine: it could be useful in the future to use anti
      tuberculous prophylaxis in selected patients treated with this purine nucleoside
      analog.

PMID- 9613992
TI  - Chronic lymphocytic leukaemia with cerebral infiltration.
AB  - Central nervous system (CNS) involvement is an extremely rare complication of
      chronic lymphocytic leukaemia (CLL). This report describes a case of stable,
      early stage CLL who developed histologically documented cerebral infiltration two
      years after the diagnosis and responded to cranial radiotherapy.

PMID- 9613993
TI  - Malignant lymphoma masquerading as multiple myeloma.
AB  - A case of non-Hodgkin's lymphoma with features mimicking that of multiple myeloma
      is reported. A 67-year-old man presented with lymphadenopathy and the classic
      constellation of symptoms and signs of multiple myeloma, including generalised
      bone pain, hypercalcemia and multiple osteolytic lesions on the skeletal survey.
      However, cervical lymph node biopsy showed diffuse large cell lymphoma and marrow
      aspirate showed infiltration with lymphoma cells different in both morphology and
      surface markers to myeloma cells.

PMID- 9613994
TI  - A new variant chromosomal translocation t(2;2)(p23;q23) in CD30+/Ki-1+ anaplastic
      large cell lymphoma.
AB  - A case with a complex chromosome abnormality with a t(2;2)(p23;q23) in CD30+/Ki
      1+ anaplastic large cell lymphoma (ALCL) is described. This chromosome aberration
      has not been reported previously in neoplastic diseases and was associated with T
      cell phenotype and involvement of the nasopharynx by the tumour.

PMID- 9613996
TI  - Teaching cases from the Royal Marsden and St Mary's Hospitals. Case 13: an
      orbital mass in a young girl.

PMID- 9613995
TI  - Cryptococcal meningitis and intracranial tuberculoma in a patient with
      Waldenstrom's macroglobulinemia treated with fludarabine.
AB  - We report a patient with Waldenstrom's Macroglobulinemia who presented with
      cryptococcal meningitis followed by an intracranial tuberculoma during the 18
      months period after termination of cytotoxic therapy with Fludarabine.
      Opportunistic infections due to intracellular organisms are extremely rare in the
      course of this malignancy and we review the predisposing factors of these
      infectious entities.

PMID- 9613997
TI  - Teaching cases from the Royal Marsden and St Mary's Hospitals. Case 14:
      persistent lymphocytosis in a middle aged smoker.

PMID- 9613998
TI  - Teaching cases from the Royal Marsden and St Mary's Hospitals. Case 15: uterine
      mass in an asymptomatic female.

PMID- 9613999
TI  - Treatment of human enterovirus infections.

PMID- 9614000
TI  - Preferential selection of heterologous G3-VP7 gene in the genetic background of
      simian rotavirus SA11 detected by using a homotypic single-VP7 gene-substitution
      reassortant.
AB  - Introduction of segmented genomes into virion is an important process in viral
      replication of rotavirus. We previously studied the assortment of the VP7 gene
      segment (encoding outer capsid protein VP7) in the genetic background of simian
      rotavirus SA11 (G serotype 3, G3) and found the preferential selection of
      homologous G3 VP7 gene over VP7 gene of heterologous G serotype (G1, G2 or G4).
      In the present study, in order to clarify whether or not VP7 gene derived from
      different G3 rotavirus (heterologous G3-VP7 gene) is also preferentially selected
      in the SA11 background, a single-VP7 gene-substitution reassortant was prepared
      from SA11 through multiple steps of coinfection with rotaviruses in vitro. The
      isolated reassortant, SNR1, possessed VP7 gene derived from canine G3 rotavirus
      K9 and all other gene segments of SA11 origin, and showed an identical growth
      characteristic to that of SA11. Amino acid sequence of K9 VP7 gene showed a high
      degree of identity (93.6%) to SA11 VP7 gene. In analysis by mixed infection and
      multiple passages of SNR1 and a single VP7 gene (with G1, G2 or G4 specificity)
      reassortant in the SA11 background, the G3-VP7 gene became predominant at early
      passage numbers. However, in mixed infection with SA11 and SNR1, homologous G3
      VP7 gene (SA11-VP7 gene) was preferentially selected into progenies over
      heterologous one (K9-VP7 gene). These results together with our previous findings
      suggested that G3-VP7 gene, irrespective of origin of species, was functionally
      adapted to the genetic background of SA11, although the homologous gene had a
      better fit with other SA11 genes than did heterologous one, providing suggestions
      for efficaciousness of multivalent reassortant rotavirus vaccine.

PMID- 9614001
TI  - Activity of N-chlorotaurine against herpes simplex- and adenoviruses.
AB  - N-chlorotaurine, an essential weak oxidant produced by stimulated human
      leukocytes, is known to have bactericidal, fungicidal and vermicidal properties.
      This study for the first time demonstrates its virucidal activity. By viral
      suspension tests at incubation times between 5 and 60 min, virus titers of both
      Herpes simplex virus type 1 and 2 were reduced about 1.3-2.9 log10 and 2.8-4.2
      log10 by 0.1 and 1%, (5.5 and 55 mM) N-chlorotaurine, respectively. Virus titer
      reduction of adenovirus type 5 between 15 and 60 min was 0.5-2.0 and 0.6-4.0
      log10, respectively, by the same concentrations of N-chlorotaurine. These
      findings support a contribution of N-chlorotaurine in destruction of pathogens
      during inflammatory reactions and also the possibility of its application as an
      antiviral agent in human medicine.

PMID- 9614002
TI  - CL387626 exhibits marked and unusual antiviral activity against respiratory
      syncytial virus in tissue culture and in cotton rats.
AB  - CL387626 (4,4'-Bis[4,6-di[3-aminophenyl-N,N-bis(2-carbamoylethyl)-sulfon ilimino]
      1,3,5-triazine-2-ylamino-bi-phenyl-2,2'-disulfonic acid, disodium salt), a
      compound synthesized by Wyeth-Ayerst Research Laboratories, was tested for its
      cytotoxicity and antiviral activity against respiratory syncytial virus (RSV) in
      tissue culture and in cotton rats. The median cell inhibitory (IC50) and median
      efficacious (EC50) concentrations of CL387626 against RSV in proliferating HEp2
      or Vero tissue culture cells were determined to be 375 and 0.25 microg/ml,
      respectively, giving the compound an apparent selective index (S.I.) of 1500.
      This compound also exhibited uncommon antiviral activity against RSV in cotton
      rats. In multiple experiments, a single 30 mg/kg dose of CL387626 administered
      intranasally 4 or 5 days prior to virus challenge, significantly inhibited
      pulmonary replication of RSV compared to that seen in control animals inoculated
      similarly with placebo (i.e. water). In contrast to these results, most lots of
      CL387626 failed to significantly inhibit pulmonary RSV replication when
      administered utilizing therapeutic administration schedules. Although some
      cytotoxicity was noted in tissue culture assays, no overt toxic effects were
      noted in any test animal, including those inoculated with > 300 mg CL387626/kg, a
      dose approximately 150 times the apparent minimal efficacious dose (i.e. 1.9
      mg/kg).

PMID- 9614003
TI  - Herpes simplex virus zosteriform lesions with adoptive transfer of immune cells:
      a murine model which mimics human recurrent disease.
AB  - Existing murine models for cutaneous herpes simplex virus type 1 (HSV-1)
      infection have limited relevance to recurrent disease in humans, since the
      infection is usually primary rather than reactivated and infection occurs in the
      absence of an established immune response. To obtain a reproducible model to
      study the effects of topical antiviral therapy on recurrent disease we have
      adapted a mouse model which employs zosteriform spread of HSV-1 in the presence
      of adoptive transfer of immunity (ATI) which mimics human recrudescent lesions.
      Mice were infected with HSV-1 by scarification at the lateroventral line of the
      neck; 2 days later, the mice received adoptive transfer of immune cells from the
      cervical lymph nodes of syngeneic mice that had been infected in the ear pinna
      with the same strain of virus 7 days earlier. ATI resulted in a heightened
      inflammatory response in the target tissues for virus replication. Virus was
      cleared more quickly from the infected tissues in comparison with mice similarly
      inoculated without ATI, however, the intensity and duration of the inflammation
      was greater. The model was then used to test the effect of a topical formulation
      of foscarnet. The results presented demonstrate that the ATI model can provide
      useful data concerning the efficacy of topical antiviral chemotherapy in man.

PMID- 9614004
TI  - Inactivation of enveloped viruses by singlet oxygen thermally generated from a
      polymeric naphthalene derivative.
AB  - Inactivation of viruses can be induced by singlet oxygen generating agents. The
      water-insoluble polymeric compound PVNE (poly (1,4-dimethyl-6-vinylnaphthalene
      1,4-endoperoxide)) is used as a storage for reactive oxygen and is able to
      produce thermally generated 1O2 in a dark-reaction. Enveloped viruses from two
      different families, Semliki Forest virus (SFV, Togaviridae) and vesicular
      stomatitis virus (VSV, Rhabdoviridae) showed a loss of infectivity of up to 8
      log10/ml (TCID50) when incubated at 37 degrees C with PVNE in buffered solutions.
      PVNE produces singlet oxygen by thermal decomposition without irradiation. Such
      chemically generated oxygen excludes reactions involving radicals (type I
      photoreactions), a problem often encountered in photodynamic processes utilizing
      dyes as sensitizers. In addition, the water insolubility of the oxygen-carrier
      allows an easy removal and recycling from aqueous solutions. Therefore, it may
      prove useful in the inactivation of viruses in biological systems and may be a
      helpful tool in studies concerning the inactivation mechanism by 1O2.

PMID- 9614005
TI  - Synergistic inhibition of HIV-1 by an antisense oligonucleotide and nucleoside
      analog reverse transcriptase inhibitors.
AB  - We have studied the effects of the gag antisense phosphorothioate oligonucleotide
      GEM 91 and mismatch antisense controls on the antiviral activities of ddC and
      other nucleoside analogs in HIV-infected MT-4 cells using a cytoprotection based
      assay. Under standard assay conditions, i.e. simultaneous incubation of drugs,
      HIV-1 IIIB and MT-4 cells, both GEM 91 and mismatch controls interacted
      synergistically with ddC resulting in an approximate 40-fold decrease in the IC50
      value of ddC; this suggests a potent but sequence non-specific effect of GEM 91.
      Under post-adsorption assay conditions, i.e. pre-incubation of virus and cells
      and removal of excess HIV before drug addition, GEM 91 exhibited synergism with
      ddC, with an approximate 5-fold decrease in ddC IC50 value. This favorable
      interaction was not seen with any of the mismatch oligonucleotides, suggesting
      the involvement of a sequence-specific mechanism of action. Similar results were
      seen with the thymidine analogs AZT and d4T in combination with GEM 91. These
      data suggest a potential role for GEM 91 and future sequence-specific antisense
      drugs in combination with nucleoside analogs for the treatment of HIV infection.
      It is essential that potential interactions between new and existing classes of
      anti-HIV drugs are studied extensively as antiretroviral drug combinations become
      increasingly more complex.

PMID- 9614006
TI  - Selected cigarette smoking initiation and quitting behaviors among high school
      students--United States, 1997.
AB  - The continuum of smoking behavior among children and adolescents can be described
      in stages of preparation, trying, experimentation, regular smoking, and nicotine
      dependence or addiction. Persons who have smoked can discontinue at any stage,
      but quitting becomes more difficult as smokers progress through the continuum and
      become increasingly dependent on nicotine. Nicotine addiction is characterized by
      a physiologic need for nicotine, including a tolerance for nicotine, withdrawal
      symptoms if an attempt is made to quit, and a high probability of relapse after
      quitting. To determine the prevalence of selected cigarette smoking initiation
      and quitting behaviors among youth, CDC analyzed data from the 1997 Youth Risk
      Behavior Survey (YRBS). Findings indicate that among U.S. high school students in
      1997, 70.2% had tried cigarette smoking. Among students who had ever tried
      cigarette smoking, 35.8% went on to smoke daily. Among those who had ever smoked
      daily, 72.9% had ever tried to quit smoking and 13.5% were former smokers.

PMID- 9614007
TI  - Cholera outbreak among Rwandan refugees--Democratic Republic of Congo, April
      1997.
AB  - In April 1997, a cholera outbreak occurred among 90,000 Rwandan refugees residing
      in three temporary camps between Kisangani and Ubundu, Democratic Republic of
      Congo (formerly Zaire). Medecins Sans Frontieres (MSF) established two referral
      medical centers and a cholera treatment center in these camps. Personnel from
      MSF, Zairean nongovernmental organizations (NGOs), and the Office of the United
      Nations High Commissioner for Refugees (UNHCR) implemented morbidity and
      mortality surveillance to monitor refugee health status. This report presents the
      findings of the surveillance system and indicates this outbreak was characterized
      by a higher death rate than that observed in previous cholera outbreaks in
      refugee populations.

PMID- 9614008
TI  - Lightning-associated deaths--United States, 1980-1995.
AB  - A lightning strike can cause death or various injuries to one or several persons.
      The mechanism of injury is unique, and the manifestations differ from those of
      other electrical injuries. In the United States, lightning causes more deaths
      than do most other natural hazards (e.g., hurricanes and tornadoes), although the
      incidence of lightning-related deaths has decreased since the 1950s. The cases
      described in this report illustrate diverse circumstances in which deaths
      attributable to lightning can occur. This report also summarizes data from the
      Compressed Mortality File of CDC's National Center for Health Statistics on
      lightning fatalities in the United States from 1980 through 1995, when 1318
      deaths were attributed to lightning.

PMID- 9614009
TI  - Plesiomonas shigelloides and Salmonella serotype Hartford infections associated
      with a contaminated water supply--Livingston County, New York, 1996.
AB  - On June 24, 1996, the Livingston County (New York) Department of Health (LCDOH)
      was notified of a cluster of diarrheal illness following a party on June 22, at
      which approximately 30 persons had become ill. This report summarizes the
      findings of the investigation, which implicated water contaminated with
      Plesiomonas shigelloides and Salmonella serotype Hartford as the cause of the
      outbreak.

PMID- 9614010
TI  - Lessons from the Bristol case. More openness--on risks and on individual
      surgeons' performance.

PMID- 9614011
TI  - The need for a national body for research misconduct. Nothing less will reassure
      the public.

PMID- 9614012
TI  - Primary care and the NHS white papers. The right principles but bedevilled by the
      detail.

PMID- 9614013
TI  - Hydroxyurea therapy for sickle cell disease in Britain. Disappointing recruitment
      despite promising results.

PMID- 9614014
TI  - Community acquired pneumonia in elderly people. Current British guidelines need
      revision.

PMID- 9614015
TI  - Cumulative risk adjusted mortality chart for detecting changes in death rate:
      observational study of heart surgery.
AB  - OBJECTIVE: To detect changes in mortality after surgery, with allowance being
      made for variations in case mix. DESIGN: Observational study of postoperative
      mortality from January 1992 to August 1995. SETTING: Regional cardiothoracic
      unit. SUBJECTS: 3983 patients aged 16 and over who had open heart operations.
      MAIN OUTCOME MEASURES: Preoperative risk factors and postoperative mortality in
      hospital within 30 days were recorded for all surgical heart operations.
      Mortality was adjusted for case mix using a preoperative estimate of risk based
      on additive Parsonnet factors. The number of operations required for statistical
      power to detect a doubling of mortality was examined, and control limits at a
      nominal significance level of P=0.01 for detection of an adverse trend were
      determined. RESULTS: Total mortality of 7.0% was 26% below the Parsonnet
      predictor (P<0.0001). There was a highly significant variation in annual case mix
      (Parsonnet scores 8.7-10.6, P<0.0001). There was no significant variation in
      mortality after adjustment for case mix (odds ratio 1-1.5, P=0.18) with
      monitoring by calendar year. With continuous monitoring, however, nominal 99%
      control limits based on 16 expected deaths were crossed on two occasions.
      CONCLUSIONS: Hospital league tables for mortality from heart surgery will be of
      limited value because year to year differences in death rate can be large (odds
      ratio 1.5) even when the underlying risk or case mix does not change. Statistical
      quality control of a single series with adjustment for case mix is the only way
      to take into account recent performance when informing a patient of the risk of
      surgery at a particular hospital. If there is an increase in the number of deaths
      the chances of the next patient surviving surgery can be calculated from the last
      16 deaths.

PMID- 9614016
TI  - Reliability of league tables of in vitro fertilisation clinics: retrospective
      analysis of live birth rates.
AB  - OBJECTIVE: To determine to what extent institutions carrying out in vitro
      fertilisation can reasonably be ranked according to their live birth rates.
      DESIGN: Retrospective analysis of prospectively collected data on live birth rate
      after in vitro fertilisation. SETTING: 52 clinics in the United Kingdom carrying
      out in vitro fertilisation over the period April 1994 to March 1995. MAIN OUTCOME
      MEASURE: Estimated adjusted live birth rate for each clinic; their rank and its
      associated uncertainty. RESULTS: There were substantial and significant
      differences between the live birth rates of the clinics. There was great
      uncertainty, however, concerning the true ranks, particularly for the smaller
      clinics. Only one clinic could be confidently ranked in the bottom quarter
      according to this measure of performance. Many centres had substantial changes in
      rank between years, even though their live birth rate did not change
      significantly. CONCLUSIONS: Even when there are substantial differences between
      institutions, ranks are extremely unreliable statistical summaries of performance
      and change in performance, particularly for smaller institutions. Any performance
      indicator should always be associated with a measure of sampling variability.

PMID- 9614017
TI  - Underperforming doctors: a postal survey of the Northern Deanery.
AB  - OBJECTIVES: To discover the perceived size of pool of doctors considered to be
      underperforming in general practice in the Northern Deanery and to discover
      whether these perceptions are based on formal assessments. DESIGN: Postal
      questionnaire. SETTING: Area covered by the Northern Deanery. SUBJECTS: Seven
      health authority directors of primary care, seven secretaries of local medical
      committees, and 14 chief officers of community health councils. RESULTS: The
      response rate was 100% for directors of primary care and secretaries of local
      medical committees and, after one reminder, 92% for chief officers of community
      health councils. Numbers of doctors perceived to be underperforming ranged from
      none to over 15 in different health authority areas. Main areas for concern were
      communication skills, clinical skills, and management skills. Patients'
      representatives were concerned about lack of power of patients and health
      authorities and doctors' lack of accountability. Health authorities were
      concerned about lack of power, identification of underperforming doctors, and
      doctors' professional loyalty. Local medical committees were concerned about the
      problem of identifying underperformance. A number of methods were used for
      identification, and there was no common method applied. CONCLUSIONS: The number
      of doctors thought to be underperforming was small. Work still needs to be done
      on developing tools that can be used in everyday practice to enable doctors to
      confirm for themselves, their colleagues, and their patients that they are
      providing an adequate level of care.

PMID- 9614018
TI  - Prevention of headache after lumbar puncture: questionnaire survey of
      neurologists and neurosurgeons in United Kingdom.

PMID- 9614019
TI  - Problems in retrieving national data on births: questionnaire survey.

PMID- 9614020
TI  - Abortion rates in England in 1995: comparative study of data from district health
      authorities.

PMID- 9614022
TI  - Alternative definitions 

PMID- 9614023
TI  - The new NHS: the plebiscite result 

PMID- 9614021
TI  - Embryonic abnormalities at medical termination of pregnancy with mifepristone and
      misoprostol during first trimester: observational study.

PMID- 9614024
TI  - Depression as a risk factor for ischaemic heart disease in men: population based
      case-control study.
AB  - OBJECTIVE: To determine the relation between depression, anxiety, and use of
      antidepressants and the onset of ischaemic heart disease. DESIGN: Population
      based case-control study. SETTING: All 5623 patients registered with one general
      practice. SUBJECTS: 188 male cases with ischaemic heart disease matched by age to
      485 male controls without ischaemic heart disease; 139 female cases with
      ischaemic heart disease matched by age to 412 female controls. MAIN OUTCOME
      MEASURE: Adjusted odds ratios calculated by conditional logistic regression.
      RESULTS: The risk of ischaemic heart disease was three times higher among men
      with a recorded diagnosis of depression than among controls of the same age (odds
      ratio 3.09; 95% confidence interval 1.33 to 7.21; P=0.009). This association
      persisted when smoking status, diabetes, hypertension, and underprivileged area
      (UPA(8)) score were included in a multivariate model (adjusted 2.75; 1.13 to
      6.69; P=0.03). Men with depression within the preceding 10 years were three times
      more likely to develop ischaemic heart disease than were the controls (3.13; 1.27
      to 7.70; P=0.01). Men with ischaemic heart disease had a higher risk of
      subsequent depression [corrected] than men without ischaemic heart disease
      (adjusted 2.34; 1.34 to 4.10; P=0.003). Depression was not a risk factor for
      ischaemic heart disease in women on multivariate analysis (adjusted 1.34; 0.70 to
      2.56; P=0.38). Anxiety and subsequent ischaemic heart disease were not
      significantly associated in men or women. CONCLUSION: Depression may be an
      independent risk factor for ischaemic heart disease in men, but not in women.

PMID- 9614025
TI  - Understanding controlled trials. Crossover trials.

PMID- 9614026
TI  - Treatment of gastro-oesophageal reflux disease in adults.

PMID- 9614028
TI  - A priori 

PMID- 9614027
TI  - Deaths from low dose paracetamol poisoning.

PMID- 9614029
TI  - Dealing with research misconduct in the United Kingdom. An American perspective
      on research integrity.

PMID- 9614030
TI  - Half of all doctors are below average.

PMID- 9614031
TI  - Five times: coincidence or something more serious?

PMID- 9614032
TI  - Competence, professional self regulation, and the public interest.

PMID- 9614033
TI  - Research assessment exercise. Single funding structure should be created for
      teaching hospitals.

PMID- 9614034
TI  - Concealed breast cancer causes delayed treatment.

PMID- 9614035
TI  - Methadone treatment is widely accepted in prisons in New South Wales.

PMID- 9614036
TI  - Measles, measles vaccination, and Crohn's disease. Second immunisation has not
      affected incidence in England.

PMID- 9614037
TI  - Adjuvant radiotherapy is advisable for small invasive breast cancers.

PMID- 9614038
TI  - Change in NHS regulations may have caused increase in malaria.

PMID- 9614039
TI  - Surgeon never said that excimer laser should no longer be used in refractive
      surgery.

PMID- 9614041
TI  - Pay rates for junior doctors' additional hours need to be adjusted.

PMID- 9614040
TI  - Milk intake and bone mineral acquisition in adolescent girls. Increases in bone
      density may be result of micronutrients in additional cereal.

PMID- 9614042
TI  - Resuscitation. Trainees' adverse experiences of the new recovery position.

PMID- 9614043
TI  - Resurgence of interest in medical oaths and codes of conduct. A universal code of
      conduct is difficult to develop.

PMID- 9614044
TI  - Colour deficient vision should not prevent a career in histopathology.

PMID- 9614045
TI  - Single assessment of risk predicted which elderly patients would fall.

PMID- 9614047
TI  - Elizabeth timgwilian davies-humphreys 

PMID- 9614046
TI  - The "Diana effect". Hospital experienced a decrease in number of admissions for
      trauma.

PMID- 9614048
TI  - King's fund launches quality service 

PMID- 9614049
TI  - Say no to viagra 

PMID- 9614050
TI  - Was the paper I wrote a fraud? see retraction box p 1700 

PMID- 9614052
TI  - Who killed cock Robin? recently, pages of newsprint have been filled with
      heartrending tales of families who lost babies under the knife of the bristol
      surgeons. This Week's panorama, the subject of an unsuccessful injunction
      application by the general medical council, alleged that the NHS system failed to
      prevent the deaths. Tony delamothe looks at the fallout for professional self
      regulation 

PMID- 9614051
TI  - Whistleblowing or professional assassination 

PMID- 9614054
TI  - Too much attention should not be paid to ranking in league tables 

PMID- 9614053
TI  - CRAM chart detects increase in number of surgical deaths 

PMID- 9614056
TI  - Better techniques would reduce headache after lumbar puncture 

PMID- 9614055
TI  - System for identifying and managing underperforming doctors is inadequate 

PMID- 9614057
TI  - A third of embryos are abnormal in medical terminations of pregnancy in first
      trimester 

PMID- 9614058
TI  - Depression may be a risk factor for heart disease in men 

PMID- 9614059
TI  - The aquaporins, blueprints for cellular plumbing systems.

PMID- 9614060
TI  - Increased Cat3-mediated cationic amino acid transport functionally compensates in
      Cat1 knockout cell lines.
AB  - Arginine transport is important for a number of biological processes in
      vertebrates, and its transport may be rate-limiting for the production of nitric
      oxide. The majority of L-Arg transport is mediated by System y+, although several
      other carriers have been kinetically defined. System y+ cationic amino acid
      transport is mediated by proteins encoded by a family of genes, Cat1, Cat2, and
      Cat3. High affinity L-arginine transport was investigated in embryonic fibroblast
      cells derived from Cat1 knockout mice that lack functional Cat1. Both wild type
      and knockout cells transport arginine with comparable Km and Vmax. However, the
      apparent affinity for lysine transport was 2.4 times lower in Cat1(-/-) cells
      when compared with wild type cells, a property characteristic of Cat3-mediated
      transport. Northern analysis-documented Cat2 mRNA increased 2-fold, whereas Cat3
      mRNA levels increased 11-fold in Cat1(-/-) relative to Cat1(+/+) cells. The low
      affinity Cat2a mRNA was not detectably expressed in these cells. Even though Cat3
      expression is normally limited to adult brain, there was a large increase in the
      amount of Cat3 protein present at the plasma membrane of Cat1(-/-) embryonic
      fibroblast cells. These results suggest that Cat3 compensates for the loss of
      functional Cat1 in cells derived from Cat1 knockout mice and mediates the
      majority of high affinity arginine transport.

PMID- 9614061
TI  - A hexameric transmembrane pore revealed by two-dimensional crystallization of the
      large mechanosensitive ion channel (MscL) of Escherichia coli.
AB  - We have established a reconstitution method of the detergent-solubilized
      recombinant large mechanosensitive ion channel of Escherichia coli (MscL) that
      yielded two-dimensional crystals. For that purpose, we have developed a new
      protocol using Triton X-100 to solubilize and purify the MscL protein. This
      protocol not only allowed an increase in the protein yield but also made it
      possible to obtain a homogeneous delipidated and reproducible preparation of the
      purified protein. When examined by the patch-clamp method MscL channels were
      found to be fully functional, exhibiting characteristic conductance and
      activation by pressure. For electron crystallography the homogeneous Triton X-100
      purified recombinant MscL was further reconstituted at low lipid-to-protein
      ratios using Bio-Beads SM2 to remove the detergent. Two-dimensional crystals,
      exhibiting a p6 plane group symmetry, have been produced and examined by negative
      stain electron microscopy. Image processing of selected micrographs yielded a
      projection map at 15-A resolution that provided the first explicit structural
      information about the molecular boundary and homohexameric organization of the
      MscL channels in the membrane bilayer.

PMID- 9614062
TI  - Superfolding of the partially unfolded core-glycosylated intermediate of human P
      glycoprotein into the mature enzyme is promoted by substrate-induced
      transmembrane domain interactions.
AB  - Misprocessed mutants of human P-glycoprotein accumulate as core-glycosylated
      intermediates in the endoplasmic reticulum and are rapidly degraded. Trypsin
      digestion was used to test for structural differences between mature and core
      glycosylated forms of P-glycoprotein. We found that the core-glycosylated wild
      type and mutant P-glycoproteins were both 100-fold more sensitive to trypsin
      compared with the mature form of the wild-type enzyme. This result suggested that
      the core-glycosylated forms of both wild-type and mutant P-glycoproteins have
      similar unfolded structures, whereas the mature enzyme is folded into a more
      compact structure. The core-glycosylated mutant P-glycoproteins could be
      converted to the mature trypsin-resistant form by synthesis in the presence of
      drug substrate. Addition of proteasome inhibitor MG-132 to stabilize the core
      glycosylated intermediate resulted in the accumulation but not maturation of the
      mutant protein. Further analysis showed that the second transmembrane domain TMD2
      also became more resistant to trypsin digestion only after coexpression with TMD1
      in the presence of substrate. Taken together, these results suggest that simply
      stabilizing the core-glycosylated intermediate is not sufficient to promote
      maturation of the processing mutants and that drug substrates induce maturation
      by promoting superfolding of the transmembrane domains.

PMID- 9614063
TI  - Molecular identification of the ryanodine receptor Ca2+ sensor.
AB  - We have investigated the molecular basis for ryanodine receptor (RyR) activation
      by Ca2+ by using site-directed mutagenesis together with functional assays
      consisting of Ca2+ release measurements and single channel recordings in planar
      lipid bilayers. We report here that a single substitution of alanine for
      glutamate at position 3885 (located in the putative transmembrane sequence M2 of
      the type 3 RyR) reduces the Ca2+ sensitivity, as measured by single channel
      activation, by more than 10,000-fold, without apparent changes in channel
      conductance and in modulation by other ligands (e.g. ATP and ryanodine). Co
      expression of the wild type and mutant RyR proteins results in the synthesis of
      single channels that have intermediate Ca2+ sensitivities. These results suggest
      that the glutamates at position 3885 of each monomer may act in a coordinated way
      to form the Ca2+ sensor in the tetrameric structure corresponding to RyR.

PMID- 9614064
TI  - Insulin, but not contraction, activates Akt/PKB in isolated rat skeletal muscle.
AB  - Insulin and muscle contraction potently stimulate glucose uptake in mammalian
      skeletal muscle. Studies in muscle and adipose tissue have shown that insulin
      induces its receptor-dependent phosphorylation of insulin receptor substrates 1
      and 2, which leads to activation of polyphosphatidylinositol (PI) 3'-kinase. In
      contrast, muscle contraction stimulates glucose transport via a mechanism that is
      independent of insulin, but the two pathways may converge downstream at the level
      of stimulation of GLUT4 translocation. In the present study, we have examined the
      role of Akt, an insulin-activated serine threonine kinase that has previously
      been shown to increase glucose transport in adipocytes. Either insulin or in
      vitro muscle contraction significantly elevated glucose transport in isolated rat
      epitrochlearis and soleus muscles. However, Akt kinase activity was significantly
      stimulated by insulin and not contraction. Moreover, wortmannin, an inhibitor of
      PI 3'-kinase, completely blocked the insulin-stimulated increase in Akt activity
      and glucose transport but did not alter either of these parameters in contracting
      muscles. The increases in Akt activity were paralleled by a decrease in the
      electrophoretic mobility of Akt, indicative of phosphorylation of Akt by an
      upstream kinase. These changes in Akt mobility appeared to be at least partially
      because of phosphorylation of Akt on serine 473. A putative downstream target of
      Akt, p70 S6 kinase, showed similar changes in mobility in response to insulin but
      not contraction. These data support the view that Akt is a downstream target of
      PI 3'-kinase and is involved in the signaling pathways involved in insulin but
      not contraction stimulation of glucose transport in skeletal muscle. These data
      provide further evidence that two distinct pathways exist for the stimulation of
      glucose transport in mammalian skeletal muscle.

PMID- 9614065
TI  - An electrophile responsive element (EpRE) regulates beta-naphthoflavone induction
      of the human gamma-glutamylcysteine synthetase regulatory subunit gene.
      Constitutive expression is mediated by an adjacent AP-1 site.
AB  - Exposure of HepG2 cells to beta-naphthoflavone (beta-NF) results in time- and
      dose-dependent increase in the steady-state mRNA levels for both the catalytic
      (GCSh) and regulatory (GCS1) subunits of gamma-glutamylcysteine synthetase (GCS)
      which catalyzes the rate-limiting step in the de novo synthesis of the cellular
      antioxidant glutathione (GSH) (Mulcahy, R. T., Wartman, M. A., Bailey, H. B., and
      Gipp, J. J. (1997) J. Biol. Chem. 272, 7445-7454). Cloning and sequencing of the
      GCS1 promoter region is reported. Regulatory sequences mediating basal and beta
      NF induced expression of the GCSl gene were identified using a series of
      promoter/reporter fusion genes transfected into HepG2 cells. Sequences directing
      basal and beta-NF induced expression were localized between nucleotides -344 and 
      242 (numbered relative to the translation start site). Mutational analyses
      indicate that basal expression of the GCSl gene is directed by a consensus AP-1
      binding site located 33 base pairs upstream of a consensus electrophile
      responsive element (EpRE) sequence; both cis-elements are capable of supporting
      beta-NF inducibility. Elimination of the inducible response requires simultaneous
      mutation of both sequences, however, in the presence of an intact EpRE the
      upstream AP-1 site is irrelevant to induction. Regulation of expression of both
      human GCS subunit genes in response to beta-NF is therefore mediated by cis
      elements satisfying the consensus core EpRE motif.

PMID- 9614066
TI  - Structure, synthesis, and molecular cloning of dermaseptins B, a family of skin
      peptide antibiotics.
AB  - Analysis of antimicrobial activities that are present in the skin secretions of
      the South American frog Phyllomedusa bicolor revealed six polycationic (lysine
      rich) and amphipathic alpha-helical peptides, 24-33 residues long, termed
      dermaseptins B1 to B6, respectively. Prepro-dermaseptins B all contain an almost
      identical signal peptide, which is followed by a conserved acidic propiece, a
      processing signal Lys-Arg, and a dermaseptin progenitor sequence. The 22-residue
      signal peptide plus the first 3 residues of the acidic propiece are encoded by
      conserved nucleotides encompassed by the first coding exon of the dermaseptin
      genes. The 25-residue amino-terminal region of prepro-dermaseptins B shares 50%
      identity with the corresponding region of precursors for D-amino acid containing
      opioid peptides or for antimicrobial peptides originating from the skin of
      distantly related frog species. The remarkable similarity found between prepro
      proteins that encode end products with strikingly different sequences,
      conformations, biological activities and modes of action suggests that the
      corresponding genes have evolved through dissemination of a conserved "secretory
      cassette" exon.

PMID- 9614067
TI  - Identification of functional domains of the human glutamate transporters EAAT1
      and EAAT2.
AB  - Glutamate transporters serve the important function of mediating removal of
      glutamate released at excitatory synapses and maintaining extracellular
      concentrations below excitotoxic levels. Excitatory amino acid transporter
      subtypes EAAT1 and EAAT2 have a high degree of sequence homology and similar
      predicted topology and yet display a number of functional differences. Several
      recombinant chimeric transporters were generated to identify domains that
      contribute to functional differences between EAAT1 and EAAT2. Wild-type
      transporters and chimeric transporters were expressed in Xenopus laevis oocytes,
      and electrogenic transport was studied under voltage clamp conditions. The
      differential sensitivity of EAAT1 and EAAT2 to transport blockers, kainate, threo
      3-methylglutamate, and (2S, 4R)-4-methylglutamate as well as L-serine-O-sulfate
      transport and chloride permeability were employed to characterize chimeric
      transporters. One particular region, transmembrane domains 9 and 10, plays an
      important role in defining these functional differences. The intracellular
      carboxyl-terminal region may also play a minor role in conferring an effect on
      chloride permeability. This study provides important insight into the
      identification of functional domains that determine differences among glutamate
      transporter subtypes.

PMID- 9614068
TI  - Enhanced cytotoxicity of nucleoside analogs by overexpression of mitochondrial
      deoxyguanosine kinase in cancer cell lines.
AB  - The cytotoxic anti-cancer purine nucleoside analogs 2-chloro-2'-deoxyadenosine
      (CdA), 9-beta-D-arabinofuranosylguanine (araG), and 2',2'-difluorodeoxyguanosine
      (dFdG) are phosphorylated by human mitochondrial deoxyguanosine kinase (dGK) in
      vitro. We overexpressed dGK as a fusion protein to the green fluorescent protein
      in the human pancreatic cancer cell lines PanC-1 and MIA PaCa-2 to determine the
      importance of dGK-mediated nucleoside analog phosphorylation. The transfected
      cells showed mitochondrial fluorescence patterns, and the mitochondrial locations
      of endogenous and overexpressed dGK were verified by Western blot analysis of
      cell extracts with polyclonal anti-dGK antibodies. The increase of dGK activity
      in the overexpressing cells was approximately 4-fold. These cell lines exhibited
      increased sensitivity to CdA, araG, and dFdG as compared with the untransfected
      parent cell lines. This is, to our knowledge, the first demonstration of a
      correlation between the activity of a mitochondrial deoxyribonucleoside kinase
      and the cytotoxicity of nucleoside analogs. Our data imply that the dGK activity
      is rate-limiting for the efficacy of nucleoside analogs in the cell lines
      investigated.

PMID- 9614069
TI  - Steroidogenic factor-1 and early growth response protein 1 act through two
      composite DNA binding sites to regulate luteinizing hormone beta-subunit gene
      expression.
AB  - Recent in vivo and in vitro studies have implicated the orphan nuclear receptor,
      steroidogenic factor-1 (SF-1), and the early growth response protein 1 (Egr-1) in
      the transcriptional regulation of the luteinizing hormone beta-subunit (LHbeta)
      gene. We have previously demonstrated the ability of SF-1 to bind to and
      transactivate the rat LHbeta gene promoter acting at a consensus gonadotrope
      specific element (GSE) located at position -127. We have now identified a second
      functional GSE site at position -59. In addition, based on electrophoretic
      mobility shift assay, in vitro translated Egr-1 is shown to bind to two putative
      Egr-1 binding sites (positions -112 and -50), which appear to be paired with the
      identified GSE sites. By transient transfection assay in pituitary-derived GH3
      cells, it was seen that Egr-1 increases promoter activity of region -207/+5 of
      the rat LHbeta gene promoter through action at both Egr-1 sites. Furthermore,
      LHbeta gene promoter activity is markedly augmented in the presence of both
      factors together relative to activity in the presence of SF-1 or Egr-1 alone (150
      fold versus 14-fold and 12-fold, respectively). These data define two composite
      SF-1-Egr-1 response-elements in the proximal LHbeta gene promoter and suggest
      that SF-1 and Egr-1 act synergistically to increase expression of the LHbeta gene
      in the gonadotrope.

PMID- 9614070
TI  - Cisplatin binding sites on human albumin.
AB  - Reactions of cisplatin (cis-[PtCl2(NH3)2]) with albumin are thought to play an
      important role in the metabolism of this anticancer drug. They are investigated
      here via (i) labeling of cisplatin with 15N and use of two-dimensional 1H,15N NMR
      spectroscopy, (ii) comparison of natural human serum albumin with recombinant
      human albumin (higher homogeneity and SH content), (iii) chemical modification of
      Cys, Met, and His residues, (iv) reactions of bound platinum with thiourea, and
      (v) gel filtration chromatography. In contrast to previous reports, it is shown
      that the major sulfur-containing binding site involves Met and not Cys-34, and
      also a N ligand, in the form of an S,N macrochelate. Additional monofunctional
      adducts involving other Met residues and Cys-34 are also observed. During the
      later stages of reactions of cisplatin with albumin, release of NH3 occurs due to
      the strong trans influence of Met sulfur, which weakens the Pt-NH3 bonds, and
      protein cross-linking is observed. The consequences of these findings for the
      biological activity of cisplatin-albumin complexes are discussed.

PMID- 9614071
TI  - IRT-1, a novel interferon-gamma-responsive transcript encoding a growth
      suppressing basic leucine zipper protein.
AB  - Interferon-gamma (IFN-gamma) inhibits proliferation of vascular smooth muscle
      cells (VSMCs) in culture and reduces arterial restenosis post-balloon
      angioplasty. The identification and characterization of IFN-gamma-specific
      transcripts in VSMCs are an important approach to discern the molecular
      mechanisms underlying vascular proliferative disease. In this report, we describe
      IRT-1, a novel mRNA transcript constitutively expressed in a number of human
      tissues, but expressed in human VSMCs only when they are stimulated with IFN
      gamma. This mRNA expression is induced >200-fold 72 h after IFN-gamma treatment.
      IRT-1 mRNA is also acutely expressed in rat carotid arteries that are injured by
      balloon angioplasty. The IRT-1 cDNA transcript encodes a basic protein that
      contains a leucine zipper motif, a core nuclear localization sequence, and a
      single strongly hydrophobic region. Constitutive IRT-1 mRNA expression in human
      peripheral blood lymphocytes is reduced when these cells are stimulated to
      proliferate. Overexpression of IRT-1 protein in VSMCs alters their morphology and
      dramatically reduces their proliferative capacity. This study suggests that IRT-1
      is an IFN-gamma-inducible factor that may regulate the progression of vascular
      proliferative diseases.

PMID- 9614072
TI  - 1alpha,25-dehydroxyvitamin D3 synergism toward transforming growth factor-beta1
      induced AP-1 transcriptional activity in mouse osteoblastic cells via its nuclear
      receptor.
AB  - The present study demonstrates 1alpha,25-dehydroxyvitamin D3 (1alpha-25-(OH)2D3)
      synergism toward transforming growth factor (TGF)-beta1-induced activation
      protein-1 (AP-1) activity in mouse osteoblastic MC3T3-E1 cells via the nuclear
      receptor of the vitamin. 1alpha-25-(OH)2D3 synergistically stimulated TGF-beta1
      induced expression of the c-jun gene in the cells but not that of the c-fos gene.
      We actually showed by a gel mobility shift assay 1alpha-25-(OH)2D3 synergism of
      TGF-beta1-induced AP-1 binding to the 12-(O-tetradecanoylphorbol-13-acetate
      response element (TRE). 1alpha-25-(OH)2D3 markedly stimulated the transient
      activity of TGF-beta1-induced AP-1 in the cells transfected with a TRE
      chloramphenicol acetyltransferase (CAT) reporter gene. Also, a synergistic
      increase in TGF-beta1-induced CAT activity was observed in the cells
      cotransfected with an expression vector encoding vitamin D3 receptor (VDR) and
      the reporter gene. However, the synergistic CAT activity was inhibited by
      pretreatment with VDR antisense oligonucleotides. In addition, in a Northern blot
      assay, we observed 1alpha-25-(OH)2D3 synergism of TGF-beta1-induced expression of
      the c-jun gene in the cells transfected with the VDR expression vector and also
      found that the synergistic action was clearly blocked by VDR antisense
      oligonucleotide pretreatment. The present study strongly suggests a novel
      positive regulation by 1alpha-25-(OH)2D3 of TGF-beta1-induced AP-1 activity in
      osteoblasts via "genomic action."

PMID- 9614073
TI  - The major adult alpha-globin gene of antarctic teleosts and its remnants in the
      hemoglobinless icefishes. Calibration of the mutational clock for nuclear genes.
AB  - The icefishes of the Southern Ocean (family Channichthyidae, suborder
      Notothenioidei) are unique among vertebrates in their inability to synthesize
      hemoglobin. We have shown previously (Cocca, E., Ratnayake-Lecamwasam, M.,
      Parker, S. K., Camardella, L., Ciaramella, M., di Prisco, G., and Detrich, H. W.,
      III (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 1817-1821) that icefishes retain
      inactive genomic remnants of adult notothenioid alpha-globin genes but have lost
      the gene that encodes adult beta-globin. Here we demonstrate that loss of
      expression of the major adult alpha-globin, alpha1, in two species of icefish
      (Chaenocephalus aceratus and Chionodraco rastrospinosus) results from truncation
      of the 5' end of the notothenioid alpha1-globin gene. The wild-type, functional
      alpha1-globin gene of the Antarctic yellowbelly rockcod, Notothenia coriiceps,
      contains three exons and two A + T-rich introns, and its expression may be
      controlled by two or three distinct promoters. Retained in both icefish genomes
      are a portion of intron 2, exon 3, and the 3'-untranslated region of the
      notothenioid alpha1-globin gene. The residual, nonfunctional alpha-globin gene,
      no longer under positive selection pressure for expression, has apparently
      undergone random mutational drift at an estimated rate of 0.12-0.33%/million
      years. We propose that abrogation of hemoglobin synthesis in icefishes most
      likely resulted from a single mutational event in the ancestral channichthyid
      that deleted the entire beta-globin gene and the 5' end of the linked alpha1
      globin gene.

PMID- 9614074
TI  - Detection of a tryptophan radical as an intermediate species in the reaction of
      horseradish peroxidase mutant (Phe-221 --> Trp) and hydrogen peroxide.
AB  - The crucial reaction intermediate in the reaction of peroxidase with hydrogen
      peroxide (H2O2), compound I, contains a porphyrin pi-cation radical in
      horseradish peroxidase (HRP), which catalyzes oxidation of small organic and
      inorganic compounds, whereas cytochrome c peroxidase (CcP) has a radical center
      on the tryptophan residue (Trp-191) and oxidizes the redox partner, cytochrome c.
      To investigate the roles of the amino acid residue near the heme active center in
      discriminating the function of the peroxidases in these two enzymes, we prepared
      a CcP-like HRP mutant, F221W (Phe-221 --> Trp). Although the rapid spectral
      scanning and stopped-flow experiments confirmed that the F221W mutant reacts with
      H2O2 to form the porphyrin pi-cation radical at the same rate as for the wild
      type enzyme, the characteristic spectral features of the porphyrin pi-cation
      radical disappeared rapidly, and were converted to the compound II-type spectrum.
      The EPR spectrum of the resultant species produced by reduction of the porphyrin
      pi-cation radical, however, was quite different from that of compound II in HRP,
      showing typical signals from a Trp radical as found for CcP. The sequential
      radical formation from the porphyrin ring to the Trp residue implies that the
      proximal Trp is a key residue in the process of the radical transfer from the
      porphyrin ring, which differentiates the function of peroxidases.

PMID- 9614075
TI  - The X11alpha protein slows cellular amyloid precursor protein processing and
      reduces Abeta40 and Abeta42 secretion.
AB  - Constitutive amyloid precursor protein (APP) metabolism results in the generation
      of soluble APP (APPs) and Abeta peptides, including Abeta40 and Abeta42-the major
      component of amyloid plaques in Alzheimer's disease brain. The phosphotyrosine
      binding (PTB) domain of X11 binds to a peptide containing a YENPTY motif found in
      the carboxyl terminus of APP. We have cloned the full-length X11 gene now
      referred to as X11alpha. Coexpression of X11alpha with APP results in
      comparatively greater levels of cellular APP and less APPs, Abeta40, and Abeta42
      recovered in conditioned medium of transiently transfected HEK 293 cells. These
      effects are impaired by a single missense mutation of either APP (Y682G within
      the YENPTY motif) or X11alpha (F608V within the PTB domain), which diminishes
      their interaction, thus demonstrating specificity. The inhibitory effect of
      X11alpha on Abeta40 and Abeta42 secretion is amplified by coexpression with the
      Swedish mutation of APP (K595N/M596L), which promotes its amyloidogenic
      processing. Pulse-chase analysis demonstrates that X11alpha prolongs the half
      life of APP from approximately 2 h to approximately 4 h. The effects of X11alpha
      on cellular APP and APPs recovery were confirmed in a 293 cell line stably
      transfected with APP. The specific binding of the PTB domain of X11alpha to the
      YENPTY motif-containing peptide of APP appears to slow cellular APP processing
      and thus reduces recovery of its soluble fragments APPs, Abeta40, and Abeta42 in
      conditioned medium of transfected HEK 293 cells. X11alpha may be involved in APP
      trafficking and metabolism in neurons and thus may be implicated in
      amyloidogenesis in normal aging and Alzheimer's disease brain.

PMID- 9614076
TI  - AMP-activated protein kinase inhibits the glucose-activated expression of fatty
      acid synthase gene in rat hepatocytes.
AB  - Although it is now clearly established that a number of genes involved in glucose
      and lipid metabolism are up-regulated by high glucose concentrations in both
      liver and adipose tissue, the signaling pathway arising from glucose to the
      transcriptional machinery is still poorly understood. We have analyzed the
      regulation of fatty acid synthase gene expression by glucose in cultured rat
      hepatocytes. Glucose (25 mM) induces an activation of the transcription of the
      fatty acid synthase gene, and this effect is markedly reduced by incubation of
      the cells with okadaic acid, an inhibitor of protein phosphatases 1 and 2A. A
      similar reduction in glucose-activated fatty acid synthase gene expression is
      obtained by incubation with 5-amino-imidazolecarboxamide riboside, a cell
      permeable activator of the AMP-activated protein kinase. Taken together, these
      results indicate that the glucose-induced expression of the fatty acid synthase
      gene involves a phosphorylation/dephosphorylation mechanism and suggest that the
      AMP-activated protein kinase plays an important role in this process. This is the
      first evidence that implicates the AMP-activated protein kinase in the regulation
      of gene expression. AMP-activated protein kinase is the mammalian analog of SNF1,
      a kinase involved in yeast in the transcriptional regulation of genes by glucose.

PMID- 9614077
TI  - The negative dominant effects of T340M mutation on mammalian pyruvate kinase.
AB  - A fundamental issue in allosteric regulatory enzymes is the identification of
      pathways of signal transmission. Rabbit muscle and kidney pyruvate kinase
      isozymes are ideal to address this issue because these isozymes exhibit different
      enzymatic regulatory patterns, and the sequence differences between these
      isozymes have identified the amino acid residues that alter their kinetic
      behavior. In an earlier study, Cheng et al. (Cheng, X., Friesen, R. H. E., and
      Lee, J. C. (1996) J. Biol. Chem. 271, 6313-6321), reported the effects of a
      threonine to methionine mutation at residue 340 in the muscle isozyme. In this
      study, the same mutation was effected in the kidney isozyme. Qualitatively, the
      same negative effects are observed in both isozymes, namely a significant
      decrease in catalytic efficiency and decrease in apparent affinity for
      phosphoenolpyruvate but no change in affinity for ADP, and a decrease in
      responsiveness to the presence of effectors, be it activator or inhibitor.
      Because the diversity in the primary sequence between these two isozymes does not
      alter the negative impact of the T340M mutation, it can be concluded that this
      mutation exerts a dominant, negative effect. The negative effects of T340M
      mutation on the kinetic properties imply that there is communication between
      residue 340 and the active site. Residue 340 is located at the 1,4 subunit
      interface; however, a T340M mutation enhances the dimerization affinity along the
      1,2 subunit interface. Thus, this study has identified a communication network
      among the active site, residue 340, and the 1,2 subunit interface.

PMID- 9614078
TI  - Interplay of the proto-oncogene proteins CrkL and CrkII in insulin-like growth
      factor-I receptor-mediated signal transduction.
AB  - The closely related proto-oncogene proteins CrkII and CrkL consist of one SH2 and
      two SH3 domains and share 60% overall homology with the highest identity within
      their functional domains. In this study we show that CrkL and CrkII may play
      overlapping but different roles in insulin-like growth factor (IGF)-I receptor
      mediated signal transduction. While both proteins are substrates involved in IGF
      I receptor signaling, they apparently demonstrate important different properties
      and different biological responses. Evidence supporting this hypothesis includes
      (a) the oncogenic potential of CrkL versus the absence of this potential in CrkII
      overexpressing cell lines, (b) the inhibition of IGF-I-dependent cell cycle
      progression by overexpression of CrkII, and (c) the differential regulation of
      the phosphorylation status of selective proteins in CrkII and CrkL overexpressing
      cell lines. In addition we demonstrate the specific association of CrkL and CrkII
      with the newly characterized IRS-4 protein, again in a differential manner.
      Whereas CrkL strongly interacts with IRS-4 via its SH2 and N-terminal SH3
      domains, CrkII interacts only via its SH2 domain, possibly explaining the
      unstable nature of IRS-4-CrkII association. The results obtained allow us to
      propose a unique mechanism of CrkL and CrkII tyrosine phosphorylation in response
      to IGF-I stimulation. Thus these highly homologous proteins apparently possess
      structural features that allow for the differential association of each protein
      with different effector molecules, thereby activating different signaling
      pathways and resulting in unique biological roles of these proteins.

PMID- 9614079
TI  - Spectinomycin kinase from Legionella pneumophila. Characterization of substrate
      specificity and identification of catalytically important residues.
AB  - The bacterium Legionella pneumophila is the responsible agent for Legionnaires'
      disease and has recently been shown to harbor a gene encoding a kinase that
      confers resistance to the aminoglycoside antibiotic spectinomycin (Suter, T. M.,
      Viswanathan, V. K., and Cianciotto, N. P. (1997) Antimicrob. Agents Chemother.
      41, 1385-1388). We report the overproduction, purification, and characterization
      of this spectinomycin kinase from an expressing system in Escherichia coli. The
      purified protein shows stringent substrate specificity for spectinomycin with Km
      = 21.5 microM and kcat = 24.2 s-1 and does not bind other aminoglycosides
      including kanamycin, amikacin, neomycin, butirosin, streptomycin, or apramycin.
      Purification of spectinomycin phosphate followed by characterization by mass
      spectrometry and 1H, 13C, and 31P NMR established the site of phosphorylation to
      be at the hydroxyl group at position 9. Thus this enzyme is designated APH(9)-Ia
      (where APH is aminoglycoside kinase). The enzyme was inactivated by the
      electrophilic ATP analogue 5'-[p-(fluorosulfonyl)benzoyl]adenosine, consistent
      with a nucleophilic residue such as Lys lining the nucleotide binding pocket.
      Site-directed mutagenesis of Lys-52 and Asp-212 to Ala confirmed that these
      residues were important for catalysis, with Lys-52 playing a potential role in
      ATP binding and Asp-212 in phosphoryl transfer. Thio and solvent isotope effect
      experiments in the presence of either Mg2+ or Mn2+ were consistent with a kinetic
      mechanism in which phosphate transfer does not contribute significantly to the
      rate-limiting step. These results establish that APH(9)-Ia is a highly specific
      antibiotic resistance kinase and provides the requisite mechanistic information
      for future structural studies.

PMID- 9614080
TI  - Identification of transcriptional activation and repression domains in human
      CCAAT/enhancer-binding protein epsilon.
AB  - Human CCAAT/enhancer-binding protein epsilon (C/EBPepsilon), a new member of the
      C/EBP family, significantly up-regulates both the mim-1 and human myeloperoxidase
      promoters, suggesting an important role for C/EBPepsilon in the transcriptional
      regulation of a subset of myeloid-specific genes. To elucidate the structure and
      function of C/EBPepsilon in transcriptional activation, amino acid residues 1
      115, 147-249, or 1-249 of C/EBPepsilon were fused to the yeast GAL4 DNA binding
      domain. These expression vectors were cotransfected with a chloramphenicol
      acetyltransferase reporter gene and, in all cell lines tested, only the GAL
      C/EBPepsilon-(1-115) fusion protein significantly activated expression from the
      chloramphenicol acetyltransferase reporter gene. Sixteen deletion mutants of
      C/EBPepsilon mapped the transactivation domain to amino acids 1-18 at the N
      terminus and revealed the presence of a transcription repression element between
      amino acid residues 116 and 162. Expression vectors containing the repression
      domain of C/EBPepsilon strongly inhibited gene transcription from TK, SV40, and
      adenoviral major late promoters bearing GAL4 binding sites. Fusion of this
      repression domain to the VP16 activation domain inhibited the transactivation
      function of VP16. Deletion of this repression domain increased gene transcription
      from a neutrophil elastase promoter-luciferase reporter. Taken together, these
      data suggest that C/EBPepsilon regulates transcription by utilizing both
      activation and repression functions.

PMID- 9614081
TI  - Markedly reduced bile acid synthesis but maintained levels of cholesterol and
      vitamin D metabolites in mice with disrupted sterol 27-hydroxylase gene.
AB  - Sterol 27-hydroxylase is important for the degradation of the steroid side chain
      in conversion of cholesterol into bile acids and has been ascribed a regulatory
      role in cholesterol homeostasis. Its deficiency causes the autosomal recessive
      disease cerebrotendinous xanthomatosis (CTX), characterized by progressive
      dementia, xanthomatosis, and accelerated atherosclerosis. Mice with a disrupted
      cyp27 (cyp27(-/-)) had normal plasma levels of cholesterol, retinol, tocopherol,
      and 1,25-dihydroxyvitamin D. Excretion of fecal bile acids was decreased (<20% of
      normal), and formation of bile acids from tritium-labeled 7alpha
      hydroxycholesterol was less than 15% of normal. Compensatory up-regulation of
      hepatic cholesterol 7alpha-hydroxylase and hydroxymethylglutaryl-CoA reductase (9
      and 2-3-fold increases in mRNA levels, respectively) was found. No CTX-related
      pathological abnormalities were observed. In CTX, there is an increased formation
      of 25-hydroxylated bile alcohols and cholestanol. In bile and feces of the cyp27(
      /-) mice only traces of bile alcohols were found, and there was no cholestanol
      accumulation. It is evident that sterol 27-hydroxylase is more important for bile
      acid synthesis in mice than in humans. The results do not support the contention
      that 27-hydroxylated steroids are critical for maintenance of cholesterol
      homeostasis or levels of vitamin D metabolites in the circulation.

PMID- 9614082
TI  - Phagocytosis of Escherichia coli by insect hemocytes requires both activation of
      the Ras/mitogen-activated protein kinase signal transduction pathway for
      attachment and beta3 integrin for internalization.
AB  - Insect hemocytes in response to lipopolysaccharide (LPS) of Gram-negative
      bacteria facilitate binding and internalization of either cell-associated or cell
      free LPS (Charalambidis, N. D., Foukas L. C., and Marmaras V. J. (1996) Eur. J.
      Biochem. 236, 200-206). An early event in LPS signaling in hemocytes involves
      protein tyrosine phosphorylation (Charalambidis N. D., Zervas C. G., Lambropoulou
      M., Katsoris P. G., and Marmaras V. J.(1995) Eur. J. Cell Biol. 67, 32-41). Here
      we report further data of LPS-mediated signal transduction responsible for
      Escherichia coli phagocytosis. We demonstrate that both adhesion of hemocytes to
      substrata and LPS stimulation can cause activation of p44(MAPK) in Ceratitis
      capitata hemocytes but with distinct kinetics indicating different functions. In
      addition, we showed that Drk, a homolog protein to the mammalian GRB2, is
      implicated in the transmission of LPS signaling, indicating that the Ras/mitogen
      activated protein kinase pathway is involved. Either the cell-free or the cell
      associated LPS appears to attach to the hemocyte surface by the same mechanism
      that is based on the cross-linking of LPS to membrane-associated p47 via the
      intermediacy of tyrosine derivatives generated by the action of phenol oxidase.
      By contrast, the cell-free LPS internalization into the hemocytes differs from
      the cell-associated LPS internalization. For E. coli internalization integrin
      receptors as well as cytoskeletal rearrangements are required, as judged by
      inhibition of E. coli internalization in the presence of the RGD peptide, beta3
      integrin antibodies, and cytochalasin D.

PMID- 9614083
TI  - Effect of band 3 subunit equilibrium on the kinetics and affinity of ankyrin
      binding to erythrocyte membrane vesicles.
AB  - The membrane-spanning protein, band 3, anchors the spectrin-based membrane
      skeleton to the lipid bilayer via the bridging protein, ankyrin. To understand
      how band 3 subunit stoichiometry influences this membrane-skeletal junction, we
      have induced changes in the band 3 association equilibrium and assayed the
      kinetics and equilibrium properties of ankyrin binding. We observe that band 3
      oligomers convert slowly to dimers and ultimately monomers following removal of
      ankyrin. Addition of excess ankyrin back to these membranes enriched in
      dissociated band 3 then shifts band 3 almost entirely to tetramers, confirming
      that the tetrameric form of band 3 constitutes the preferred oligomeric state of
      ankyrin binding. 4, 4'-Diisothiocyanostilbene-2,2'-disulfonic acid (DIDS)
      labeling of band 3, which is shown to shift most of the band 3 population to
      dimers, eliminates the majority of ankyrin-binding sites on the membrane and
      greatly reduces retention of band 3 in detergent-extracted membrane skeletons.
      Furthermore, DIDS- modified membranes lack all low affinity ankyrin-binding sites
      and roughly half of all high affinity sites. Since labeled membranes lack the
      rapid kinetic phase of ankyrin binding and exhibit only half of the normal
      amplitude of the slow kinetic phase, it can be concluded that the rapid phase of
      ankyrin association involves low affinity sites and the slow phase involves high
      affinity sites. A model accounting for these data and most previous data on
      ankyrin-band 3 interactions is provided.

PMID- 9614084
TI  - Platelets interact with soluble and insoluble collagens through
      characteristically different reactions.
AB  - Platelet interaction with soluble and insoluble collagens was characterized
      through binding studies. In contrast to resting platelets, cells reacted with
      activators, TS2/16 (integrin alpha2 beta1-activating antibody), thrombin,
      collagen-related peptide, or ADP, exhibited specific soluble collagen binding
      that is Mg2+-dependent, but inhibited by prostaglandin I2, Ca2+, and Gi9 (anti
      integrin alpha2 beta1 antibody). Each platelet has 1500-3500 soluble collagen
      binding sites, with a dissociation constant of 3. 5-9 x 10(-8) M. This is the
      first study to show the specific binding of soluble collagen to platelets; our
      data strongly suggest that the receptor is integrin alpha2 beta1 after it becomes
      activated upon platelet activation. These results suggest that activation of
      platelets transforms integrin alpha2 beta1 to a state with higher affinity
      binding sites for soluble collagen. The soluble collagen-platelet interaction was
      compared with the platelet interaction with fibrillar collagen, which has until
      now not been demonstrated to bind specifically to platelets. Here, we
      demonstrated specific, biphasic fibrillar collagen binding. One phase is rapid
      and metal ion-independent, and accounts for most of the binding. The other phase
      is slow and Mg2+-dependent. The characteristic differences in the specific
      bindings of soluble and fibrous collagens demonstrate the different contributions
      of two different collagen receptors.

PMID- 9614085
TI  - Ectopic potassium uptake in trk1 trk2 mutants of Saccharomyces cerevisiae
      correlates with a highly hyperpolarized membrane potential.
AB  - Null trk1 trk2 mutants of Saccharomyces cerevisiae exhibit a low-affinity uptake
      of K+ and Rb+. We show that this low-affinity Rb+ uptake is mediated by several
      independent transporters, and that trk1Delta cells and especially trk1Delta
      trk2Delta cells are highly hyperpolarized. Differences in the membrane potentials
      were assessed for sensitivity to hygromycin B and by flow cytometric analyses of
      cellular DiOC6(3) fluorescence. On the basis of the latter analyses, it is
      proposed that Trk1p and Trk2p are involved in the control of the membrane
      potential, preventing excessive hyperpolarizations. K+ starvation and nitrogen
      starvation hyperpolarize both TRK1 TRK2 and trk1Delta trk2Delta cells, thus
      suggesting that other proteins, in addition to Trk1p and Trk2p, participate in
      the control of the membrane potential. The HAK1 K+ transporter from
      Schwanniomyces occidentalis suppresses the K+-defective transport of trk1Delta
      trk2Delta cells but not the high hyperpolarization, and the HKT1 K+ transporter
      from wheat suppresses both defects, in the presence of Na+. We discuss the
      mechanism involved in the control of the membrane potential by Trk1p and Trk2p
      and the causal relationship between the high membrane potential (negative inside)
      of trk1Delta trk2Delta cells and its ectopic transport of alkali cations.

PMID- 9614086
TI  - Phosphorylation sites in the autoinhibitory domain participate in p70(s6k)
      activation loop phosphorylation.
AB  - Here we have employed p70(s6k) truncation and point mutants to elucidate the role
      played by the carboxyl-terminal autoinhibitory domain S/TP phosphorylation sites
      in kinase activation. Earlier studies showed that truncation of the p70(s6k)
      amino terminus severely impaired kinase activation but that this effect was
      reversed by deleting the carboxyl terminus, which in parallel led to deregulation
      of Thr229 phosphorylation in the activation loop (Dennis, P. B., Pullen, N.,
      Kozma, S. C., and Thomas, G. (1996) Mol. Cell. Biol. 16, 6242-6251). In this
      study, substitution of acidic residues for the four autoinhibitory domain S/TP
      sites mimics the carboxyl-terminal deletion largely by rescuing kinase activation
      caused by the amino-terminal truncation. However, these mutations do not
      deregulate Thr229 phosphorylation, suggesting the involvement of another
      regulatory element in the intact kinase. This element appears to be Thr389
      phosphorylation, because substitution of an acidic residue at this position in
      the p70(s6k) variant containing the S/TP mutations leads to a large increase in
      basal Thr229 phosphorylation and kinase activity. In contrast, an alanine
      substitution at Thr389 blocks both responses. Consistent with these data, we show
      that a mutant harboring the acidic S/TP and Thr389 substitutions is an excellent
      in vitro substrate for the newly identified Thr229 kinase, phosphoinositide
      dependent kinase-1 (Pullen, N., Dennis, P. B., Andjelkovic, M., Dufner, A.,
      Kozma, S., Hemmings, B. A., and Thomas, G. (1998) Science 279, 707-710), whereas
      phosphoinositide-dependent kinase-1 poorly utilizes the two p70(s6k) variants
      that have only one set of mutations. These findings indicate that phosphorylation
      of the S/TP sites, in cooperation with Thr389 phosphorylation, controls Thr229
      phosphorylation through an intrasteric mechanism.

PMID- 9614087
TI  - Phosphoinositide 3-OH kinase activates the beta2 integrin adhesion pathway and
      induces membrane recruitment of cytohesin-1.
AB  - Signal transduction through phosphoinositide 3-OH kinase (PI 3-kinase) has been
      implicated in the regulation of lymphocyte adhesion mediated by integrin
      receptors. Cellular phosphorylation products of PI 3-kinases interact with a
      subset of pleckstrin homology (PH) domains, a module that has been shown to
      recruit proteins to cellular membranes. We have recently identified cytohesin-1,
      a cytoplasmic regulator of beta2 integrin adhesion to intercellular adhesion
      molecule 1. We describe here that expression of a constitutively active PI 3
      kinase is sufficient for the activation of Jurkat cell adhesion to intercellular
      adhesion molecule 1, and for enhanced membrane association of cytohesin-1. Up
      regulation of cell adhesion by PI 3-kinase and membrane association of endogenous
      cytohesin-1 is abrogated by overexpression of the isolated cytohesin-1 PH domain,
      but not by a mutant of the PH domain which fails to associate with the plasma
      membrane. The PH domain of Bruton's tyrosine kinase (Btk), although strongly
      associated with the plasma membrane, had no effect on either membrane recruitment
      of cytohesin-1 or on induction of adhesion by PI 3-kinase. Having delineated the
      critical steps of the beta2 integrin activation pathway by biochemical and
      functional analyses, we conclude that PI 3-kinase activates inside-out signaling
      of beta2 integrins at least partially through cytohesin-1.

PMID- 9614088
TI  - Characterization of a highly conserved FAD-binding site in human monoamine
      oxidase B.
AB  - Monoamine oxidase B (MAO B) catalyzes the oxidative deamination of biogenic and
      xenobiotic amines. The oxidative step is coupled to the reduction of an
      obligatory cofactor, FAD, which is covalently linked to the apoenzyme at Cys397.
      Our previous studies identified two noncovalent flavin-binding regions in MAO B
      (residues 6-34 and 39-46) (Kwan, S.-W., Lewis, D. A., Zhou, B. P., and Abell, C.
      W. (1995) Arch. Biochem. Biophys. 316, 385-391; Zhou, B. P., Lewis, D. A., Kwan,
      S.-W., Kirksey, T. J., and Abell, C. W. (1995) Biochemistry 34, 9526-9531). In
      these regions, Glu34 and Tyr44 were found to be required for the initial binding
      of FAD. By comparing sequences with enzymes in the oxidoreductase family, we now
      have found an additional FAD-binding site in MAO B (residues 222-227), which is
      highly conserved across species (human, bovine, and rat). This conserved sequence
      contains adjacent glycine and aspartate residues (Gly226 and Asp227). Based on
      the x-ray crystal structures of several oxidoreductases (Eggink, G., Engel, H.,
      Vriend, G., Terpstra, P., and Witholt, B. (1990) J. Mol. Biol. 212, 135-142; Van
      Driessche, G., Kol, M., Chen, Z.-W., Mathews, F. S., Meyer, T. E., Bartsch, R.
      G., Cusanovich, M. A., and Van Beeumen, J. J. (1996) Protein Sci. 5, 1753-1764),
      the Gly residue at the end of a beta-strand facilitates a sharp turn and extends
      the beta-carbonyl group of Asp to interact with the 3'-hydroxyl group of the
      ribityl chain of FAD. To assess the hypothesis that Gly226 and Asp227 are
      involved in FAD binding in MAO B, site-specific mutants that encode substitutions
      at these positions were prepared and expressed in mammalian COS-7 cells. Our
      results indicate that Gly226 and the beta-carbonyl group of Asp227 are required
      for covalent flavinylation and catalytic activity of MAO B, but not for
      noncovalent binding of FAD. Our studies also reveal that mutagenesis at Glu34 and
      Tyr44 not only interferes with covalent flavinylation and catalytic activity of
      MAO B, but also with noncovalent binding of FAD. Based on these collective
      results, we propose that the coupling of FAD to the MAO B apoenzyme is a
      multistep process.

PMID- 9614089
TI  - The Aspergillus nidulans cnxF gene and its involvement in molybdopterin
      biosynthesis. Molecular characterization and analysis of in vivo generated
      mutants.
AB  - The product of the Aspergillus nidulans cnxF gene was found by biochemical
      analysis of cnxF mutants to be involved in the conversion of precursor Z to
      molybdopterin. Mutants cnxF1242 and cnxF8 accumulate precursor Z, while the level
      of molybdopterin is undetectable. The DNA sequence of the cnxF gene was
      determined, and the inferred protein of 560 amino acids was found to contain a
      central region (residues around 157 to 396) similar in sequence to the
      prokaryotic proteins MoeB, which is thought to encode molybdopterin synthase
      sulfurylase, ThiF, required for thiamine biosynthesis, and HesA, involved in
      heterocyst formation, as well as eukaryotic ubiquitin-activating protein E1.
      Based on these similarities, a possible mechanism of action is discussed.
      Sequence comparisons indicate the presence of one and possibly two nucleotide
      binding motifs, Gly-X-Gly-X-X-Gly, as well as two metal binding Cys-X-X-Cys
      motifs in this central region of the CnxF protein. Seven in vivo generated A.
      nidulans cnxF mutants were found to have amino acid substitutions of conserved
      residues within this central region of similarity to molybdopterin synthase
      sulfurylase, indicating that these seven amino acids are essential and that this
      domain is crucial for function. Of these seven, the cnxF1285 mutation results in
      the replacement of Gly-178, the last glycine residue of the N-proximal Gly-X-Gly
      X-X-Gly motif, indicating that this motif is essential. Mutation of the conserved
      Arg-208, also probably involved in nucleotide binding, leads to a loss-of
      function phenotype in cnxF200. Alteration of Cys-263, the only conserved Cys
      residue (apart from the metal binding motifs), in cnxF472 suggests this residue
      as a candidate for thioester formation between molybdopterin synthase and the
      sulfurylase. Substitution of Gly-160 in two independently isolated mutants,
      cnxF21 and cnxF24, results in temperature-sensitive phenotypes and indicates that
      this residue is important in protein conformation. The C-terminal CnxF stretch
      (residues 397-560) shows substantial sequence conservation to a yeast
      hypothetical protein, Yhr1, such conservation between species suggesting that
      this region has function. Not inconsistent with this proposition is the
      observation that mutant cnxF8 results from loss of the 34 C-terminal residues of
      CnxF. There is no obvious similarity of the CnxF C-terminal region with other
      proteins of known function. Two cnxF transcripts are found in low abundance and
      similar levels were observed in nitrate- or ammonium-grown cells.

PMID- 9614090
TI  - Macrophage migration inhibitory factor interactions with glutathione and S
      hexylglutathione.
AB  - Macrophage migration inhibitory factor (MIF) has been reported to interact with
      glutathione and S-hexylglutathione and to possess glutathione S-transferase
      activity. However, contrary to these reports, a recent NMR study concluded that
      MIF shows no affinity for glutathione. Re-examination of the glutathione-MIF
      interactions indicates that the reported increase in fluorescence upon addition
      of glutathione is because of pH-induced unfolding of the protein and not to any
      direct interactions. Circular dichroism shows that MIF remains folded from pH 4.5
      7.5 but is 50% unfolded at pH 2.9 +/- 0.2. The reported increase in fluorescence
      can be achieved by acid titration. Under strongly buffered conditions, no
      fluorescence change is observed upon addition of glutathione. In contrast to the
      results with glutathione, MIF binds S-hexylglutathione with a Kd of 2.5 +/- 0.6
      mM. Using NMR spectroscopy, a binding site which clusters around the N-terminal
      proline was identified. These data indicate that the binding site for S
      hexylglutathione is the same as the catalytic site for the dopachrome tautomerase
      activity of MIF. Consequently, the binding of S-hexylglutathione as well as
      hexanethiol inhibits this catalytic activity.

PMID- 9614091
TI  - Transcriptional regulation of endothelial nitric-oxide synthase by
      lysophosphatidylcholine.
AB  - We have shown that lysophosphatidylcholine (lyso-PC) increases endothelial nitric
      oxide synthase (eNOS) expression at the transcriptional level (Zembowicz, A.,
      Tang, J.-L., and Wu, K. K. (1995) J. Biol. Chem. 270, 17006-17010). To elucidate
      the mechanism by which lyso-PC increases the eNOS transcription, we identified
      Sp1 sites at -104 to -90 and PEA3 sites at -40 to -24 as being involved in lyso
      PC-induced promoter activity. Site-directed mutagenesis of Sp1 sites resulted in
      a marked reduction of basal and lyso-PC-induced activity whereas PEA3 site
      mutation abrogated response to lyso-PC. Band shift assays revealed that lyso-PC
      augmented Sp1 binding activity. Pretreatment of cells or nuclear extracts with
      okadaic acid reduced the Sp1 binding activity. Furthermore, okadaic acid
      treatment abrogated the lyso-PC induced promoter augmentation. Lyso-PC increased
      the nuclear extract protein phosphatase 2A (PP2A) activity, which was suppressed
      by okadaic acid treatment. These results suggest that lyso-PC up-regulates eNOS
      transcription by a PP2A-dependent increase in Sp1 binding activity.

PMID- 9614092
TI  - Monoterpene synthases from common sage (Salvia officinalis). cDNA isolation,
      characterization, and functional expression of (+)-sabinene synthase, 1,8-cineole
      synthase, and (+)-bornyl diphosphate synthase.
AB  - Common sage (Salvia officinalis) produces an extremely broad range of cyclic
      monoterpenes bearing diverse carbon skeletons, including members of the p
      menthane (1,8-cineole), pinane (alpha- and beta-pinene), thujane (isothujone),
      camphane (camphene), and bornane (camphor) families. An homology-based polymerase
      chain reaction cloning strategy was developed and used to isolate the cDNAs
      encoding three multiproduct monoterpene synthases from this species that were
      functionally expressed in Escherichia coli. The heterologously expressed
      synthases produce (+)-bornyl diphosphate, 1, 8-cineole, and (+)-sabinene,
      respectively, as their major products from geranyl diphosphate. The bornyl
      diphosphate synthase also produces significant amounts of (+)-alpha-pinene, (+)
      camphene, and (+/-)-limonene. The 1,8-cineole synthase produces significant
      amounts of (+)- and (-)-alpha-pinene, (+)- and (-)-beta-pinene, myrcene and (+)
      sabinene, and the (+)-sabinene synthase produces significant quantities of gamma
      terpinene and terpinolene. All three enzymes appear to be translated as
      preproteins bearing an amino-terminal plastid targeting sequence, consistent with
      the plastidial origin of monoterpenes in plants. Deduced sequence analysis and
      size exclusion chromatography indicate that the recombinant bornyl diphosphate
      synthase is a homodimer, whereas the other two recombinant enzymes are monomeric,
      consistent with the size and subunit architecture of their native enzyme
      counterparts. The distribution and stereochemistry of the products generated by
      the recombinant (+)-bornyl diphosphate synthase suggest that this enzyme might
      represent both (+)-bornyl diphosphate synthase and (+)-pinene synthase which were
      previously assumed to be distinct enzymes.

PMID- 9614093
TI  - Binding site for blood coagulation factor Xa involving residues 311-325 in factor
      Va.
AB  - Factor Va inactivation by activated protein C is associated with cleavages at
      Arg306, Arg506, and Arg679 with Arg306 cleavage causing the major activity loss.
      To study functional roles of the Arg306 region, overlapping 15-mer peptides
      representing the sequence of factor Va residues 271-345 were synthesized and
      screened for anticoagulant activities. The peptide containing residues 311-325
      (VP311) noncompetitively inhibited prothrombin activation by factor Xa, but only
      in the presence of factor Va. Fluorescence studies showed that VP311 bound to
      fluorescence-labeled 5-dimethylaminonaphthalene-1-sulfonyl-Glu-Gly-Arg factor Xa
      in solution with a Kd of 70 microM. Diisopropylphosphoryl factor Xa and factor Xa
      but not factor VII/VIIa or prothrombin bound to immobilized VP311 with relatively
      high affinity. These results support the hypothesis that residues 311-325, which
      are positioned between the A1 and A2 domains of factor Va and likely exposed to
      solvent, contribute to the binding of factor Xa by factor Va. Based on this
      hypothesis, it is suggested that cleavage by activated protein C at Arg306 in
      factor Va not only severs the covalent connection between the A1 and A2 domains
      but also disrupts the environment and structure of residues 311-325, thereby down
      regulating the binding of factor Xa to factor Va.

PMID- 9614094
TI  - Phosphatidylinositol 3-kinase contributes to cell volume regulation through
      effects on ATP release.
AB  - Regulated changes in cell volume represent a signal that modulates a broad range
      of cell and organ functions. In HTC hepatoma cells, increases in volume are
      coupled to membrane ion permeability through a pathway involving (i) ATP efflux,
      (ii) autocrine stimulation of P2 receptors, and (iii) increases in anion
      permeability and Cl- efflux, contributing to recovery of volume toward basal
      values. Based on recent evidence that cell volume increases also stimulate
      phosphoinositide kinases, the purpose of these studies was to determine if
      phosphatidylinositol 3-kinase (PI 3-kinase) modulates these pathways. Exposure of
      cells to hypotonic buffer (20 or 40% less NaCl) caused an initial increase in
      cell volume and stimulated a rapid increase in ATP release. Subsequent opening of
      Cl- channels was followed by recovery of cell volume toward basal values, despite
      the continuous presence of hypotonic buffer. Inhibition of PI 3-kinase with
      wortmannin (Ki = 3 nM) significantly inhibited both the rate of volume recovery
      and activation of Cl- currents; similar results were obtained with LY294002 (10
      microM). Additionally, current activation was inhibited by intracellular dialysis
      with antibodies specific for the 110-kDa catalytic subunit of PI 3-kinase. Since
      release of ATP is a critical element in the volume-regulatory pathway, the role
      of PI 3-kinase on volume-stimulated ATP release was assessed. Both wortmannin and
      LY294002 decreased basal and volume-stimulated ATP permeability but had no effect
      on the current response to exogenous ATP (10 microM). These findings indicate
      that PI 3-kinase plays a significant role in regulation of cell volume and
      suggest that the effects are mediated in part through modulation of cellular ATP
      release.

PMID- 9614095
TI  - Antagonists of the receptor-G protein interface block Gi-coupled signal
      transduction.
AB  - The carboxyl terminus of heterotrimeric G protein alpha subunits plays an
      important role in receptor interaction. We demonstrate that peptides
      corresponding to the last 11 residues of Galphai1/2 or Galphao1 impair agonist
      binding to A1 adenosine receptors, whereas Galphas or Galphat peptides have no
      effect. Previously, by using a combinatorial library we identified a series of
      Galphat peptide analogs that bind rhodopsin with high affinity (Martin, E. L.,
      Rens-Domiano, S., Schatz, P. J., and Hamm, H. E. (1996) J. Biol. Chem. 271, 361
      366). Native Galphai1/2 peptide as well as several analogs were tested for their
      ability to modulate agonist binding or antagonist-agonist competition using cells
      overexpressing human A1 adenosine receptors. Three peptide analogs decreased the
      Ki, suggesting that they disrupt the high affinity receptor-G protein interaction
      and stabilize an intermediate affinity state. To study the ability of the
      peptides to compete with endogenous Galphai proteins and block signal
      transduction in a native setting, we measured activation of G protein-coupled K+
      channels through A1 adenosine or gamma-aminobutyric acid, type B, receptors in
      hippocampal CA1 pyramidal neurons. Native Galphai1/2, peptide, and certain analog
      peptides inhibited receptor-mediated K+ channel gating, dependent on which
      receptor was activated. This differential perturbation of receptor-G protein
      interaction suggests that receptors that act on the same G protein can be
      selectively disrupted.

PMID- 9614096
TI  - Reconstitution of beta-adrenergic modulation of large conductance, calcium
      activated potassium (maxi-K) channels in Xenopus oocytes. Identification of the
      camp-dependent protein kinase phosphorylation site.
AB  - The human large conductance, calcium-activated potassium (maxi-K) channel (alpha
      and beta subunits) and beta2-adrenergic receptor genes were coexpressed in
      Xenopus oocytes in order to study the mechanism of beta-adrenergic modulation of
      channel function. Isoproterenol and forskolin increased maxi-K potassium channel
      currents in voltage-clamped oocytes expressing the receptor and both channel
      subunits by 33 +/- 5% and 35 +/- 8%, respectively, without affecting current
      activation or inactivation. The percentage of stimulation by isoproterenol and
      forskolin was not different in oocytes coexpressing the alpha and beta subunits
      versus those expressing the only the alpha subunit, suggesting that the alpha
      subunit is the target for regulation. The stimulatory effect of isoproterenol was
      almost completely blocked by intracellular injection of the cyclic AMP dependent
      protein kinase (cAMP-PK) regulatory subunit, whereas injection of a cyclic GMP
      dependent protein kinase inhibitory peptide had little effect, indicating that
      cellular coupling of beta2-adrenergic receptors to maxi-K channels involves
      endogenous cAMP-PK. Mutation of one of several potential consensus cAMP-PK
      phosphorylation sites (serine 869) on the alpha subunit almost completely
      inhibited beta-adrenergic receptor/channel stimulatory coupling, whereas
      forskolin still stimulated currents moderately (16 +/- 4%). These data
      demonstrate that physiological coupling between beta2 receptors and maxi-K
      channels occurs by the cAMP-PK mediated phosphorylation of serine 869 on the
      alpha subunit on the channel.

PMID- 9614097
TI  - Slow feedback inhibition of calcium release-activated calcium current by calcium
      entry.
AB  - In many nonexcitable cells, depletion of the inositol 1,4, 5-trisphosphate
      sensitive store activates Ca2+ influx, a process termed store-operated Ca2+
      entry. In rat basophilic leukemia cells, emptying of the stores activates a
      highly selective Ca2+ release-activated Ca2+ current (CRAC), ICRAC. We have
      recently found that ICRAC activates in an essentially all-or-none manner when the
      current is evoked by receptor stimulation, dialysis with inositol 1, 4,5
      trisphosphate via the patch pipette, or through the Ca2+ATPase inhibitor
      thapsigargin (Parekh, A. B., Fleig, A., and Penner, R. (1997) Cell 89, 973-980).
      Regulatory mechanisms must therefore operate to control the overall amount of
      Ca2+ that enters through CRAC channels. Such mechanisms include membrane
      potential and protein kinase C. In the present study, we have investigated
      additional inhibitory pathways that serve to determine just how much Ca2+ can
      enter through ICRAC. We have directly measured the current using the whole cell
      patch clamp technique. We report the presence of a slow Ca2+-dependent
      inactivation mechanism that curtails Ca2+ entry through CRAC channels. This
      inactivation mechanism is switched on by Ca2+ entering through CRAC channels, and
      therefore constitutes a slow negative feedback process. Although it requires a
      rise in intracellular Ca2+ for activation, it maintains CRAC channels inactive
      even under conditions that lower intracellular Ca2+ levels. The inactivation
      mechanism does not involve store refilling, protein phosphorylation, G proteins,
      nor Ca2+-dependent enzymes. It accounts for up to 70% of the total inactivation
      of ICRAC, and therefore appears to be a dominant inhibitory mechanism. It is
      likely to be an important factor that shapes the profile of the Ca2+ signal in
      these nonexcitable cells.

PMID- 9614098
TI  - Isolation and characterization of the gene (CLS1) encoding cardiolipin synthase
      in Saccharomyces cerevisiae.
AB  - In eukaryotic cells, cardiolipin (CL) synthase catalyzes the final step in the
      synthesis of CL from phosphatidylglycerol and CDP-diacylglycerol. CL and its
      synthesis are localized predominantly to the mitochondrial inner membrane, and CL
      is generally thought to be an essential component of many mitochondrial
      processes. By using homology searches for genes potentially encoding phospholipid
      biosynthetic enzymes, we have cloned the gene (CLS1) encoding CL synthase in
      Saccharomyces cerevisiae. Overexpression of the CLS1 gene under its endogenous
      promoter or the inducible GAL1 promoter in yeast and expression of CLS1 in
      baculovirus-infected insect cells resulted in elevated CL synthase activity.
      Disruption of the CLS1 gene in a haploid yeast strain resulted in the loss of CL
      synthase activity, no detectable CL, a 5-fold elevation in phosphatidylglycerol
      levels, and lack of staining of mitochondria by a dye with high affinity for CL.
      The cls1::TRP1 null mutant grew on both fermentable and non-fermentable carbon
      sources but more poorly on the latter. The level and activity of cytochrome c
      oxidase was normal, and a dye whose accumulation is dependent on membrane proton
      electrochemical potential effectively stained the mitochondria. These results
      definitively identify the gene encoding the CL synthase of yeast.

PMID- 9614099
TI  - Rustmicin, a potent antifungal agent, inhibits sphingolipid synthesis at inositol
      phosphoceramide synthase.
AB  - Rustmicin is a 14-membered macrolide previously identified as an inhibitor of
      plant pathogenic fungi by a mechanism that was not defined. We discovered that
      rustmicin inhibits inositol phosphoceramide synthase, resulting in the
      accumulation of ceramide and the loss of all of the complex sphingolipids.
      Rustmicin has potent fungicidal activity against clinically important human
      pathogens that is correlated with its sphingolipid inhibition. It is especially
      potent against Cryptococcus neoformans, where it inhibits growth and sphingolipid
      synthesis at concentrations <1 ng/ml and inhibits the enzyme with an IC50 of 70
      pM. This inhibition of the membrane-bound enzyme is reversible; moreover,
      rustmicin is nearly equipotent against the solubilized enzyme. Rustmicin was
      efficacious in a mouse model for cryptococcosis, but it was less active than
      predicted from its in vitro potency against this pathogen. Stability and drug
      efflux were identified as two factors limiting rustmicin's activity. In the
      presence of serum, rustmicin rapidly epimerizes at the C-2 position and is
      converted to a gamma-lactone, a product that is devoid of activity. Rustmicin was
      also found to be a remarkably good substrate for the Saccharomyces cerevisiae
      multidrug efflux pump encoded by PDR5.

PMID- 9614100
TI  - Characterization of CCAAT/enhancer-binding protein alpha as a cyclic AMP
      responsive nuclear regulator.
AB  - The alpha isoform of CCAAT/enhancer-binding protein (C/EBPalpha) is a
      transcription factor that regulates expression of genes linked to adipose
      differentiation and hepatic nutrient metabolism. Recently, our laboratory has
      characterized a role for C/EBPalpha in mediating hormonal responsiveness. For
      example, the cAMP responsiveness of the phosphoenolpyruvate carboxykinase gene
      promoter in liver requires synergism among the cAMP response element-binding
      protein (CREB), C/EBPalpha, and activator protein-1. In the present study, we
      show that C/EBPalpha can functionally substitute for CREB in this cAMP response
      unit, i.e. cAMP responsiveness can occur in the absence of CREB. This observation
      is physiologically relevant since both CREB and C/EBPalpha have been shown to
      bind with high affinity to the cAMP response element in this particular promoter.
      Structure/function analysis of C/EBPalpha identified specific mutations that
      differentially affected its constitutive and protein kinase A-inducible
      activities. This finding suggests that the mechanism whereby C/EBPalpha mediates
      constitutive transactivation is distinct from that whereby it mediates cAMP
      responsiveness. These data support the hypothesis that C/EBPalpha plays a
      critical role in metabolism, in part by participating in the hormonal regulation
      of expression of metabolically important genes.

PMID- 9614101
TI  - Cyclin D3 is rate-limiting for the G1/S phase transition in fibroblasts.
AB  - D-type cyclins are induced in response to mitogens and are believed to control
      progression through the G1 phase of the cell cycle by activating their
      corresponding kinase partners (cyclin-dependent kinases). To investigate the
      function of individual D-type cyclins we have constructed rat fibroblast lines
      that allow controllable overexpression of a human cyclin D3 cDNA. Overexpression
      of cyclin D3 led to accelerated passage through G1 in actively proliferating
      cells with no effect on the overall population doubling time. In cells re
      entering the division cycle from a quiescent state, cyclin D3 caused an even more
      dramatic advancement of S phase entry. Accelerated progression through G0/G1-to-S
      correlated with premature phosphorylation of the pRb tumor suppressor protein and
      its relatives, p107 and p130. We conclude that cyclin D3 can act as a rate
      limiting G1 cyclin and that this effect involves, in part, the premature
      phosphorylation of critical substrates.

PMID- 9614102
TI  - The CBL-related protein CBLB participates in FLT3 and interleukin-7 receptor
      signal transduction in pro-B cells.
AB  - The FLT3 receptor tyrosine kinase and its ligand, FL, play an important role in
      early hematopoietic development. We have found that CBLB, a recently
      characterized molecule closely related to the CBL protooncogene product, is
      phosphorylated on tyrosine(s) following FL treatment of JEA2 human pro-B cells
      and THP1 monocytic cells. Treatment of JEA2 cells with interleukin (IL)-7 induces
      CBLB phosphorylation as well. FL and IL-7, respectively, induce and increase
      association of tyrosine-phosphorylated SHC and the p85 subunit of
      phosphatidylinositol 3'-kinase with CBLB. In these cells, CBLB constitutively
      binds the GRB2 adaptor predominantly through its N-terminal SH3 domain, to form a
      complex that is distinct from the GRB2.CBL and GRB2.SOS1 complexes. Together with
      the fact that CBLB is consistently found in blast cells from acute leukemias and
      in peripheral blood mononuclear cells, this suggests that CBLB has a role in
      tyrosine kinase-regulated signaling pathways in many hematolymphoid cells.

PMID- 9614103
TI  - Insulin regulation of glucose-6-phosphate dehydrogenase gene expression is
      rapamycin-sensitive and requires phosphatidylinositol 3-kinase.
AB  - Glucose-6-phosphate dehydrogenase (G6PDH) controls the flow of carbon through the
      pentose phosphate pathway and also produces NADPH needed for maintenance of
      reduced glutathione and reductive biosynthesis. Hepatic expression of G6PDH is
      known to respond to several dietary and hormonal factors, but the mechanism
      behind regulation of this expression has not been characterized. We show that
      insulin similarly induces expression of endogenous hepatic G6PDH and a reporter
      construct containing 935 base pairs of the G6PDH promoter linked to luciferase in
      transient transfection assays. Using well tested and structurally distinct
      inhibitors of Ras farnesylation, lovastatin and B581, and a specific inhibitor of
      mitogen-activated protein kinase kinase activation, PD 98059, we show that the
      Ras/Raf/mitogen-activated protein kinase pathway is not utilized for the insulin
      induced stimulation of G6PDH gene expression in primary rat hepatocytes.
      Similarly, using well characterized inhibitors of phosphatidylinositol 3-kinase,
      wortmannin and LY 294002, we show that PI 3-kinase activity is necessary for the
      induction of G6PDH expression by insulin. Rapamycin, an inhibitor of FRAP
      protein, which is involved in the activation of pp70 S6 kinase, blocks the
      insulin induction of G6PDH, suggesting that S6 kinase is also necessary for the
      insulin induction of G6PDH expression.

PMID- 9614104
TI  - Proximal sequences of the aldolase A fast muscle-specific promoter direct nerve-
      and activity-dependent expression in transgenic mice.
AB  - Muscle activity is known to modulate the muscle fiber phenotype. Changes in
      muscle activity (normal or experimentally induced) lead to modifications of the
      expression status of several muscle-specific genes. However, the transcription
      regulatory elements involved in the adaptative response are mainly unknown. The
      aldolase A muscle-specific promoter, pM, is expressed in adult fast twitch muscle
      with a preferential expression in fast glycolytic-2B fibers. Its activity is
      induced during postnatal muscle maturation, suggesting a role of nerve and/or
      muscle activity. Indeed, denervation of gastrocnemius in newborn mice prevented
      the activation of the promoter in this muscle, despite the nerve-independent
      formation of 2B fibers. Although the nerve was necessary for pM onset during
      development, denervating the gastrocnemius in adults had only mild effects on pM
      activity. By contrast, a transgene including the pM proximal regulatory sequences
      that are sufficient to reproduce the 2B fiber-specific expression of the
      endogenous promoter was shown to be highly sensitive to both neonatal and adult
      denervation. Transgenes containing muscle-specific pM proximal promoter elements
      were used to delineate the regulatory elements involved in this response to
      innervation and changes in the contractile activity pattern. Nerve- and activity
      dependent elements could be localized in the 130-base pair-long proximal promoter
      region of the human aldolase A gene.

PMID- 9614105
TI  - Biosynthesis of O-N-acetylglucosamine-linked glycans in Trypanosoma cruzi.
      Characterization of the novel uridine diphospho-N-acetylglucosamine:polypeptide N
      acetylglucosaminyltransferase-catalyzing formation of N-acetylglucosamine alpha1-
      >O-threonine.
AB  - In this study, we have characterized the activity of a uridine diphospho-N
      acetylglucosamine:polypeptide-alpha-N-acetylglucosaminylt ransferase (O-alpha
      GlcNAc-transferase) from Trypanosoma cruzi. The activity is present in microsomal
      membranes and is responsible for the addition of O-linked alpha-N
      acetylglucosamine to cell surface proteins. This preparation adds N
      acetylglucosamine to a synthetic peptide KPPTTTTTTTTKPP containing the consensus
      threonine-rich dodecapeptide encoded by T. cruzi MUC gene (Di Noia, J. M.,
      Sanchez D. O., and Frasch, A. C. C. (1995) J. Biol. Chem. 270, 24146-24149).
      Incorporation of N-[3H]acetylglucosamine is linearly dependent on incubation time
      and concentration of enzyme and substrate. The transferase activity has an
      optimal pH of 7.5- 8.5, requires Mn2+, is unaffected by tunicamycin or
      amphomycin, and is strongly inhibited by UDP. The optimized synthetic peptide
      acceptor for the cytosolic O-GlcNAc-transferase (YSDSPSTST) (Haltiwanger, R. S.,
      Holt, G. D., and Hart, G. W. (1990) J. Biol. Chem. 265, 2563-2568) is not a
      substrate for this enzyme. The glycosylated KPPTTTTTTTTKPP product is susceptible
      to base-catalyzed beta-elimination, and the presence of N-acetylglucosamine alpha
      linked to threonine is supported by enzymatic digestion and nuclear magnetic
      resonance data. These results describe a unique biosynthetic pathway for T. cruzi
      surface mucin-like molecules, with potential chemotherapeutic implications.

PMID- 9614106
TI  - Three high mobility group-like sequences within a 48-base pair enhancer of the
      Col2a1 gene are required for cartilage-specific expression in vivo.
AB  - To understand the molecular mechanisms by which mesenchymal cells differentiate
      into chondrocytes, we have used the gene for an early and abundant marker of
      chondrocytes, the mouse pro-alpha1(II) collagen gene (Col2a1), to delineate a
      minimal sequence needed for chondrocyte-specific expression and to identify the
      DNA-binding proteins that mediate its activity. We show here that a 48-base pair
      (bp) Col2a1 intron 1 sequence specifically targets the activity of a heterologous
      promoter to chondrocytes in transgenic mice. Mutagenesis studies of this 48-bp
      element identified three separate sites (sites 1-3) that were essential for its
      chondrocyte-specific enhancer activity in both transgenic mice and transient
      transfections. Mutations in sites 1 and 2 also severely inhibited the chondrocyte
      specific enhancer activity of a 468-bp Col2a1 intron 1 sequence in vivo. SOX9, an
      SRY-related high mobility group (HMG) domain transcription factor, was previously
      shown to bind site 3, to bend the 48-bp DNA at this site, and to strongly
      activate this 48-bp enhancer as well as larger Col2a1 enhancer elements. All
      three sites correspond to imperfect binding sites for HMG domain proteins and
      appear to be involved in the formation of a large chondrocyte-specific complex
      between the 48-bp element, Sox9, and other protein(s). Indeed, mutations in each
      of the three HMG-like sites of the 48-bp element, which abolished chondrocyte
      specific expression of reporter genes in transgenic mice and in transiently
      transfected cells, inhibited formation of this complex. Overall our results
      suggest a model whereby both Sox9 and these other proteins bind to several HMG
      like sites in the Col2a1 gene to cooperatively control its expression in
      cartilage.

PMID- 9614107
TI  - Chondrocyte-specific enhancer elements in the Col11a2 gene resemble the Col2a1
      tissue-specific enhancer.
AB  - Type XI collagen and type II collagen are coexpressed in all cartilage, and both
      are essential for normal cartilage differentiation and skeletal morphogenesis.
      This laboratory has recently identified a 48-base pair (bp) enhancer element in
      the type II collagen gene Col2a1 that contains several HMG-type protein-binding
      sites and that can direct chondrocyte-specific expression in transient
      transfection and in transgenic mice. The present study has identified two short
      chondrocyte-specific enhancer elements within a region in the 5' portion of the
      type XI collagen gene Col11a2 that has previously been shown to influence
      chondrocyte-specific expression in transgenic mice. These Col11a2 enhancer
      elements, like the Col2a1 enhancer, contain several sites with homology to the
      high mobility group (HMG) protein-binding consensus sequence. In electrophoretic
      mobility shift assays, the Col11a2 elements formed a DNA-protein complex that was
      dependent on the presence of the HMG-like sites. It had the same mobility as the
      complex formed with the Col2a1 48-bp enhancer and appeared to contain the same or
      similar proteins, including SOX9. The Col11a2 elements directed gene expression
      in transient transfections of chondrocytes but not fibroblasts, and their
      activity was abolished by mutation of the HMG-like sites. Ectopically expressed
      SOX9 activated these enhancers in non-chondrocytic cells, as it also activates
      the Col2a1 enhancer. Finally, the Col11a2 enhancer elements both directed
      transgene expression to cartilage in developing mouse embryos. Overall, our
      results indicate that the two Col11a2 chondrocyte-specific enhancer elements
      share many similarities with the Col2a1 48-bp enhancer. These similarities
      suggest the existence of a genetic program designed to coordinately regulate the
      expression of these and perhaps other genes involved in the chondrocyte
      differentiation pathway.

PMID- 9614108
TI  - CXCR4 sequences involved in coreceptor determination of human immunodeficiency
      virus type-1 tropism. Unmasking of activity with M-tropic Env glycoproteins.
AB  - The interaction of human immunodeficiency virus type 1 (HIV-1) with CD4 and one
      of a cadre of chemokine receptors triggers conformational changes in the HIV-1
      envelope (Env) glycoprotein that lead to membrane fusion. The coreceptor activity
      of the second extracellular loop of CXCR4, which is restricted to dual tropic and
      T-tropic strains, was insensitive to the removal of charged residues either
      singly or in combinations by alanine scanning mutagenesis or to the conversion of
      acidic residues to lysine. Conversion of Asp-187 to a neutral residue exclusively
      unmasked activity with M-tropic Env in fusion and infection experiments.
      Insertion of the D187V mutation into chimeras containing extracellular loop 2 of
      CXCR4 in a CXCR2 framework also resulted in the acquisition of M-tropic
      coreceptor activity. The independence of CXCR4 coreceptor activity from charged
      residues and the extension of its repertoire by removing Asp-187 suggest that
      this interaction is not electrostatic and that coreceptors have the potential to
      be utilized by a spectrum of Env, which may be masked by charged amino acids in
      extracellular domains. These findings indicate that the primary structural
      determinants of coreceptors that program reactivity with M-, dual, and T-tropic
      Env are surprisingly subtle and that relatively insignificant changes in CXCR4
      can dramatically alter utilization by Env of varying tropism.

PMID- 9614109
TI  - Tropomyosin and troponin regulation of wild type and E93K mutant actin filaments
      from Drosophila flight muscle. Charge reversal on actin changes actin-tropomyosin
      from on to off state.
AB  - In the Drosophila flight muscle actin mutant E93K there is a charge reversal on
      the surface of actin close to the proposed position of tropomyosin when it is in
      the off state. Using a quantitative in vitro motility assay we have found that
      the wild type Drosophila ACT88F actin behaved like rabbit skeletal muscle actin
      when tropomyosin and troponin were added at pCa5 and pCa9. In contrast the effect
      of tropomyosin upon the E93K mutant actin filament movement was completely
      different from wild type and resembled the response of wild type with
      tropomyosin+troponin at pCa9 (i.e. the filaments were switched off). Velocity of
      E93K actin did not increase, and the fraction of filaments motile was reduced to
      less than 15% by adding up to 30 nM tropomyosin. When myosin subfragment-1
      modified by N-ethylmaleimide was mixed with mutant E93K actin-tropomyosin
      filaments we observed that it restored motility of the filaments to the level
      observed with E93K actin alone. We conclude that electrostatic charge on the
      surface of domain 2 of actin plays a critical role in determining the state of
      actin-tropomyosin that is a central feature of the steric blocking mechanism of
      actin filament regulation.

PMID- 9614110
TI  - p38 Mitogen-activated protein kinase is a critical component of the redox
      sensitive signaling pathways activated by angiotensin II. Role in vascular smooth
      muscle cell hypertrophy.
AB  - Angiotensin II induces an oxidant stress-dependent hypertrophy in cultured
      vascular smooth muscle cells. To investigate the growth-related molecular targets
      of H2O2, we examined the redox sensitivity of agonist-stimulated activation of
      the mitogen-activated protein kinase (MAPK) family. We show here that angiotensin
      II elicits a rapid increase in intracellular H2O2 and a rapid and robust
      phosphorylation of both p42/44MAPK (16-fold) and p38MAPK (15-fold). However,
      exogenous H2O2 activates only p38MAPK (14-fold), and diphenylene iodonium, an
      NADH/NADPH oxidase inhibitor, attenuates angiotensin II-stimulated
      phosphorylation of p38MAPK, but not p42/44MAPK. Furthermore, in cells stably
      transfected with human catalase, angiotensin II-induced intracellular H2O2
      generation is almost completely blocked, resulting in inhibition of
      phosphorylation of p38MAPK, but not p42/44MAPK, and a subsequent partial decrease
      in angiotensin II-induced hypertrophy. Specific inhibition of either the p38MAPK
      pathway with SB203580 (4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4
      pyridyl)1H- imidaz ole) or the p42/44MAPK pathway with PD98059 (2-(2'-amino-3'
      methoxyphenyl)oxanaphthalen-4-one) also partially, but significantly, attenuates
      angiotensin II-induced hypertrophy; however, simultaneous blockade of both
      pathways has an additive inhibitory effect, indicating that the hypertrophic
      response to angiotensin II requires parallel, independent activation of both MAPK
      pathways. These results provide the first evidence that p38MAPK is a critical
      component of the oxidant stress (H2O2)-sensitive signaling pathways activated by
      angiotensin II in vascular smooth muscle cells and indicate that it plays a
      crucial role in vascular hypertrophy.

PMID- 9614111
TI  - Mammalian prenylcysteine carboxyl methyltransferase is in the endoplasmic
      reticulum.
AB  - Prenylcysteine carboxyl methyltransferase (pcCMT) is the third of three enzymes
      that posttranslationally modify C-terminal CAAX motifs and thereby target CAAX
      proteins to the plasma membrane. Here we report the molecular characterization
      and subcellular localization of the first mammalian (human myeloid) pcCMT. The
      deduced amino acid sequence of mammalian pcCMT predicts a multiple membrane
      spanning protein with homologies to the yeast pcCMT, STE14, and the mammalian
      band 3 anion transporter. The human gene complemented a ste14 mutant. pcCMT mRNAs
      were ubiquitously expressed in human tissues. An anti-pcCMT antiserum detected a
      33-kDa protein in myeloid cell membranes. Ectopically expressed recombinant pcCMT
      had enzymatic activity identical to that observed in neutrophil membranes.
      Mammalian pcCMT was not expressed at the plasma membrane but rather restricted to
      the endoplasmic reticulum. Thus, the final enzyme in the sequence that modifies
      CAAX motifs is located in membranes topologically removed from the CAAX protein
      target membrane.

PMID- 9614112
TI  - Crystal structures of reaction intermediates of L-2-haloacid dehalogenase and
      implications for the reaction mechanism.
AB  - Crystal structures of L-2-haloacid dehalogenase from Pseudomonas sp. YL complexed
      with monochloroacetate, L-2-chlorobutyrate, L-2-chloro-3-methylbutyrate, or L-2
      chloro-4-methylvalerate were determined at 1.83-, 2.0-, 2.2-, and 2.2-A
      resolutions, respectively, using the complex crystals prepared with the S175A
      mutant, which are isomorphous with those of the wild-type enzyme. These
      structures exhibit unique structural features that correspond to those of the
      reaction intermediates. In each case, the nucleophile Asp-10 is esterified with
      the dechlorinated moiety of the substrate. The substrate moieties in all but the
      monochloroacetate intermediate have a D-configuration at the C2 atom. The overall
      polypeptide fold of each of the intermediates is similar to that of the wild-type
      enzyme. However, it is clear that the Asp-10-Ser-20 region moves to the active
      site in all of the intermediates, and the Tyr-91-Asp-102 and Leu-117-Arg-135
      regions make conformational changes in all but the monochloroacetate
      intermediates. Ser-118 is located near the carboxyl group of the substrate
      moiety; this residue probably serves as a binding residue for the substrate
      carboxyl group. The hydrophobic pocket, which is primarily composed of the Tyr
      12, Gln-42, Leu-45, Phe-60, Lys-151, Asn-177, and Trp-179 side chains, exists
      around the alkyl group of the substrate moiety. This pocket may play an important
      role in stabilizing the alkyl group of the substrate moiety through hydrophobic
      interactions, and may also play a role in determining the stereospecificity of
      the enzyme. Moreover, a water molecule, which is absent in the substrate-free
      enzyme, is present in the vicinities of the carboxyl carbon of Asp-10 and the
      side chains of Asp-180, Asn-177, and Ala-175 in each intermediate. This water
      molecule may hydrolyze the ester intermediate and its substrate. These findings
      crystallographically demonstrate that the enzyme reaction proceeds through the
      formation of an ester intermediate with the enzyme's nucleophile Asp-10.

PMID- 9614113
TI  - Crystal structure of RNA helicase from genotype 1b hepatitis C virus. A feasible
      mechanism of unwinding duplex RNA.
AB  - Crystal structure of RNA helicase domain from genotype 1b hepatitis C virus has
      been determined at 2.3 A resolution by the multiple isomorphous replacement
      method. The structure consists of three domains that form a Y-shaped molecule.
      One is a NTPase domain containing two highly conserved NTP binding motifs.
      Another is an RNA binding domain containing a conserved RNA binding motif. The
      third is a helical domain that contains no beta-strand. The RNA binding domain of
      the molecule is distinctively separated from the other two domains forming an
      interdomain cleft into which single stranded RNA can be modeled. A channel is
      found between a pair of symmetry-related molecules which exhibit the most
      extensive crystal packing interactions. A stretch of single stranded RNA can be
      modeled with electrostatic complementarity into the interdomain cleft and
      continuously through the channel. These observations suggest that some form of
      this dimer is likely to be the functional form that unwinds double stranded RNA
      processively by passing one strand of RNA through the channel and passing the
      other strand outside of the dimer. A "descending molecular see-saw" model is
      proposed that is consistent with directionality of unwinding and other
      physicochemical properties of RNA helicases.

PMID- 9614114
TI  - Mutations at the domain interface of GSalpha impair receptor-mediated activation
      by altering receptor and guanine nucleotide binding.
AB  - G protein alpha subunits consist of two domains, a GTPase domain and a helical
      domain. Receptors activate G proteins by catalyzing replacement of GDP, which is
      buried between these two domains, with GTP. Substitution of the homologous
      alphai2 residues for four alphas residues in switch III, a region that changes
      conformation upon GTP binding, or of one nearby helical domain residue decreases
      the ability of alphas to be activated by the beta-adrenergic receptor and by
      aluminum fluoride. Both sets of mutations increase the affinity of alphas for the
      beta-adrenergic receptor, based on an increased amount of high affinity binding
      of the beta-adrenergic agonist, isoproterenol. The mutations also decrease the
      rate of receptor-mediated activation and disrupt the ability of the beta
      adrenergic receptor to increase the apparent affinity of alphas for the GTP
      analog, guanosine 5'-O-(3-thiotriphosphate). Simultaneous replacement of the
      helical domain residue and one of the four switch III residues with the
      homologous alphai2 residues restores normal receptor-mediated activation,
      suggesting that the defects caused by mutations at the domain interface are due
      to altered interdomain interactions. These results suggest that interactions
      between residues across the domain interface are involved in two key steps of
      receptor-mediated activation, promotion of GTP binding and subsequent receptor-G
      protein dissociation.

PMID- 9614115
TI  - The human proteinase-activated receptor-3 (PAR-3) gene. Identification within a
      Par gene cluster and characterization in vascular endothelial cells and
      platelets.
AB  - Proteolytically activated receptors (PARs) represent an emerging subset of seven
      transmembrane G protein-coupled receptors that mediate cell activation events by
      receptor cleavage at distinct scissile bonds located within receptor amino
      termini. Differential genomic blotting using a yeast artificial chromosome known
      to contain the PAR-1 and PAR-2 genes identified the PAR-3 gene within a PAR gene
      cluster spanning approximately 100 kilobases at 5q13. The PAR-3 gene is
      relatively small (approximately 12 kilobases); and, like the PAR-1 and PAR-2
      genes, it displays a two-exon structure, with the majority of the coding sequence
      and the proteolytic cleavage site contained within the larger second exon.
      Sequence analysis of the 5'-flanking region demonstrates that the promoter is
      TATA-less, similar to that seen with PAR-1, with the identification of nucleic
      acid motifs potentially involved in transcriptional gene regulation, including AP
      1, GATA, and octameric sequences. PAR-3 transcripts were apparent in human
      vascular endothelial cells, although at considerably lower levels than those of
      PAR-1 and not significantly modulated by the endothelial cell stimulus tumor
      necrosis factor-alpha. Likewise, although PAR-3 mRNA was evident in human
      platelets, receptor cell surface expression was modest (approximately 10%)
      compared with that of PAR-1. Thus, although PAR-3 is postulated to represent a
      second thrombin receptor, its modest endothelial cell and platelet expression
      suggest that PAR-3 activation by alpha-thrombin is less relevant for
      physiological responses in these mature cells. Rather, given its disparately
      greater expression in megakaryocytes (and megakaryocyte-like human
      erythroleukemia cells), a regulatory role in cellular development (by protease
      activation) could be postulated.

PMID- 9614116
TI  - Molecular features of the collagen V heparin binding site.
AB  - A heparin binding region is known to be present within the triple helical part of
      the alpha1(V) chain. Here we show that a recombinant alpha1(V) fragment (Ile824
      to Pro950), referred to as HepV, is sufficient for heparin binding at
      physiological ionic strength. Both native individual alpha1(V) chains and HepV
      are eluted at identical NaCl concentrations (0.35 M) from a heparin-Sepharose
      column, and this binding can be inhibited specifically by the addition of free
      heparin or heparan sulfate. In contrast, a shorter 23-residue synthetic peptide,
      containing the putative heparin binding site in HepV, fails to bind heparin.
      Interestingly, HepV promotes cell attachment, and HepV-mediated adhesion is
      inhibited specifically by heparin or heparan sulfate, indicating that this region
      might behave as an adhesive binding site. The same site is equally functional on
      triple helical molecules as shown by heparin-gold labeling. However, the
      affinities for heparin of each of the collagen V molecular forms tested are
      different and increase with the number of alpha1(V) chains incorporated in the
      molecules. Molecular modeling of a sequence encompassing the putative HepV
      binding sequence region shows that all of the basic residues cluster on one side
      of the helical face. A highly positively charged ring around the molecule is thus
      particularly evident for the alpha1(V) homotrimer. This could strengthen its
      interaction with the anionic heparin molecules. We propose that a single heparin
      binding site is involved in heparin-related glycosaminoglycans-collagen V
      interactions, but the different affinities observed likely modulate cell and
      matrix interactions between collagen V and heparan sulfate proteoglycans in
      tissues.

PMID- 9614117
TI  - Cdc2-cyclin B phosphorylates p70 S6 kinase on Ser411 at mitosis.
AB  - The carboxyl terminus of p70 S6 kinase (p70(s6k)) has a set of Ser and Thr
      residues (Ser411, Ser418, Ser424, and Thr421) phosphorylated in vivo by an
      unidentified kinase(s). These Ser/Thr sites are immediately followed by proline,
      a motif that is commonly seen in the substrates of cyclin-dependent kinases (Cdk)
      and mitogen-activated protein kinases. A previous study has shown that Cdc2
      (Cdk1) indeed phosphorylates these p70(s6k) Ser/Thr residues in vitro. Here, we
      demonstrate that Cdc2-cyclin B complex phosphorylates Ser411 in the KIRSPRR
      sequence, whereas other Cdk-cyclin complexes including those containing Cdk2,
      Cdk4, or Cdk6 do not. Additionally, Ser411 phosphorylation in vivo was increased
      at mitosis in parallel with Cdc2 activation, and it was suppressed by a dominant
      negative form of Cdc2. These data indicate that p70(s6k) is a physiological
      substrate of Cdc2-cyclin B in mitosis. Since the activity of p70(s6k) is low
      during mitosis, Cdc2-cyclin B may play a role in inactivating p70(s6k) during
      mitosis, where protein synthesis is suppressed.

PMID- 9614118
TI  - Mammalian mitochondrial methionyl-tRNA transformylase from bovine liver.
      Purification, characterization, and gene structure.
AB  - The mammalian mitochondrial methionyl-tRNA transformylase (MTFmt) was partially
      purified 2,200-fold from bovine liver mitochondria using column chromatography.
      The polypeptide responsible for MTFmt activity was excised from a sodium dodecyl
      sulfate-polyacrylamide gel and the amino acid sequences of several peptides were
      determined. The cDNA encoding bovine MTFmt was obtained and its nucleotide
      sequence was determined. The deduced amino acid sequence of the mature form of
      MTFmt consists of 357 amino acid residues. This sequence is about 30% identical
      to the corresponding Escherichia coli and yeast mitochondrial MTFs. Kinetic
      parameters governing the formylation of various tRNAs were obtained. Bovine MTFmt
      formylates its homologous mitochondrial methionyl-tRNA and the E. coli initiator
      methionyl-tRNA (Met-tRNAfMet) with essentially equal efficiency. The E. coli
      elongator methionyl-tRNA (Met-tRNAmMet) was also formylated although with
      somewhat less favorable kinetics. These results suggest that the substrate
      specificity of MTFmt is not as rigid as that of the E. coli MTF which clearly
      discriminates between the bacterial initiator and elongator Met-tRNAs. These
      observations are discussed in terms of the presence of a single tRNAMet gene in
      mammalian mitochondria.

PMID- 9614119
TI  - Protein kinase C-alpha activity inversely modulates invasion and growth of
      intestinal cells.
AB  - The phorbol ester phorbol 12-myristate 13-acetate induces remarkable phenotypic
      changes in intestinal HT-29 M6 cells; these changes consist of loss of homotypic
      adhesion and inactivation of E-cadherin. In parallel, cell growth is retarded. We
      have transfected HT-29 M6 cells with an activated form of the conventional
      protein kinase Calpha (cPK-Calpha). Expression of this isoform induced the
      acquisition of a scattered phenotype, similar to that adopted by cells after
      addition of phorbol 12-myristate 13-acetate, with very low cell-to-cell
      aggregation and undetectable levels of functional E-cadherin. These cell clones
      were highly motile and rapidly invaded embryonic chick heart fragments.
      Furthermore, cells expressing activated-cPK-Calpha showed decreased proliferation
      in comparison to control clones. We have also studied how these two apparently
      antagonistic changes affect the tumorigenic ability of HT-29 M6 cells. When the
      different cell clones were xenografted into athymic mice, the effect on cell
      growth seemed to predominate. Expression of activated-cPK-Calpha significantly
      reduced the size of the tumors; the cells with the highest level of expression
      did not even form subcutaneous tumors. Besides their smaller size, the morphology
      of these tumors was clearly different from those originated by HT-29 M6 cells,
      and they could be defined as infiltrative on anatomo-pathological basis. These
      results indicate that cPK-Calpha controls both cell-to-cell adhesion and
      proliferation of intestinal cells.

PMID- 9614120
TI  - Vascular permeability factor/vascular endothelial cell growth factor-mediated
      permeability occurs through disorganization of endothelial junctional proteins.
AB  - Vascular permeability factor/vascular endothelial growth factor stimulates
      endothelial proliferation, angiogenesis, and increased vascular permeability in
      vivo. We investigated mechanisms of vascular permeability factor-mediated
      endothelial monolayer permeability changes in vitro. [14C]Albumin flux across
      endothelial monolayers was measured following a 90-min exposure to vascular
      permeability factor (660 pM). Vascular permeability factor increased albumin flux
      to 3.4 times that of control albumin flux. Endothelial monolayers were also
      incubated for 90 min with vascular permeability factor plus Go6976 (10 nM),
      staurosporine (1 microM), wortmannin (10 nM), AG126 (1 and 2.67 microM), and
      PD98059 (20 microM). Vascular permeability factor-mediated permeability was not
      blocked by Go6976, an antagonist of "classical" protein kinase C, staurosporine,
      a pan-protein kinase C antagonist, nor wortmannin, a PI3-kinase blocker, but was
      blocked by incubation with AG126 or PD98059, inhibitors of mitogen-activated
      protein kinase activation. Immunofluorescent staining of the junctional proteins
      VE-cadherin and occludin showed a loss of these proteins from the endothelial
      junction that was prevented by co-incubation with AG126 or PD98059. These data
      demonstrate that vascular permeability factor increases albumin permeability
      across endothelial monolayers in vitro and suggests that permeability increases
      through rearrangement of endothelial junctional proteins involving the mitogen
      activated protein kinase signal transduction pathway.

PMID- 9614121
TI  - Direct demonstration of Ca2+ binding defects in sarco-endoplasmic reticulum Ca2+
      ATPase mutants overexpressed in COS-1 cells transfected with adenovirus vectors.
AB  - Single mutations of specific amino acids within the membrane-bound region of the
      sarco-endoplasmic reticulum Ca2+ (SERCA)-1 ATPase interfere with Ca2+ inhibition
      of ATPase phosphorylation by Pi (1), suggesting that these residues may be
      involved in complexation of two Ca2+ that are known to bind to the enzyme.
      However, direct measurements of Ca2+ binding in the absence of ATP have been
      limited by the low quantities of available mutant protein. We have improved the
      transfection efficiency by means of recombinant adenovirus vectors, yielding
      sufficient expression of wild type and mutant SERCA-1 ATPase for measurements of
      Ca2+ binding to the microsomal fraction of the transfected cells. We find that in
      the presence of 20 microM Ca2+ and in the absence of ATP, the Glu771 --> Gln,
      Thr799 --> Ala, Asp800 --> Asn, and Glu908 --> Ala mutants exhibit negligible
      binding, indicating that the oxygen functions of Glu771, Thr799, Asp800, and
      Glu908 are involved in interactions whose single disruption causes major changes
      in the highly cooperative "duplex" binding. Total loss of Ca2+ binding is
      accompanied by loss of Ca2+ inhibition of the Pi reaction. We also find that, at
      pH 7.0, the Glu309 --> Gln and the Asn796 --> Ala mutants bind approximately half
      as much Ca2+ as the wild type ATPase and do not interfere with Ca2+ inhibition of
      the Pi reaction. At pH 6.2, the Glu309 --> Gln mutant does not bind any Ca2+, and
      its phosphorylation by Pi is not inhibited by Ca2+. On the contrary, the Asn796 -
      > Ala mutant retains the behavior displayed at pH 7.0. This suggests that in the
      Glu309 --> Gln mutant, ionization of acidic functions in other amino acids (e.g.
      Glu771 and Asp800) occurs as the pH is shifted, thereby rendering Ca2+ binding
      possible. In the Asn796 --> Ala mutant, on the other hand, the Glu309 carboxylic
      function allows binding of inhibitory Ca2+ even at pH 6.2. In all cases
      mutational interference with the inhibition of the Pi reaction by Ca2+ can be
      overcome by raising the Ca2+ concentration to the mM range, consistent with a
      general effect of mutations on the affinity of the ATPase for Ca2+.

PMID- 9614122
TI  - Golgi localization and functionally important domains in the NH2 and COOH
      terminus of the yeast CLC putative chloride channel Gef1p.
AB  - GEF1 encodes the single CLC putative chloride channel in yeast. Its disruption
      leads to a defect in iron metabolism (Greene, J. R., Brown, N. H., DiDomenico, B.
      J., Kaplan, J., and Eide, D. (1993) Mol. Gen. Genet. 241, 542-553). Since
      disruption of GEF2, a subunit of the vacuolar H+-ATPase, leads to a similar
      phenotype, it was previously suggested that the chloride conductance provided by
      Gef1p is necessary for vacuolar acidification. We now show that gef1 cells indeed
      grow less well at less acidic pH. However, no defect in vacuolar acidification is
      apparent from quinacrine staining, and Gef1p co-localizes with Mnt1p in the
      medial Golgi. Thus, Gef1p may be important in determining Golgi pH. Systematic
      alanine scanning of the amino and the carboxyl terminus revealed several regions
      essential for Gef1p localization and function. One sequence (FVTID) in the amino
      terminus conforms to a class of sorting signals containing aromatic amino acids.
      This was further supported by point mutations. Alanine scanning of the carboxyl
      terminus identified a stretch of roughly 25 amino acids which coincides with the
      second CBS domain, a conserved protein motif recently identified. Mutations in
      the first CBS domain also destroyed proper function and localization. The second
      CBS domain can be transplanted to the amino terminus without loss of function,
      but could not be replaced by the corresponding domain of the homologous mammalian
      channel ClC-2.

PMID- 9614124
TI  - Isolation, purification, and characterization of a collagen-associated serpin,
      caspin, produced by murine colon adenocarcinoma cells.
AB  - A 45-kDa serpin secreted by a murine colon adenocarcinoma cell line, colon26, was
      isolated, purified, and characterized. It was found to bind specifically to type
      I collagen with high affinity and to type III collagen with lower affinity.
      Immunohistochemical studies of murine embryonic tissues showed a specific
      distribution of this collagen-associated serpin, named caspin, in relation to the
      formation of bone, cartilage, teeth, and basement membrane. The expression of
      caspin in high and low lung metastatic subclones of colon26 cell lines was
      inversely correlated with their metastatic capacity: low lung metastatic cells
      secreted higher amounts of caspin than their high lung metastatic counterparts.
      Caspin also demonstrated high homology with human pigment epithelium-derived
      factor/early population doubling level cDNA-1, which reportedly induces neuronal
      differentiation of human retinoblastoma cells and is expressed in association
      with G0 growth arrest. These findings suggest that caspin/pigment epithelium
      derived factor/early population doubling level cDNA-1 is a novel factor that
      might play a crucial role in embryogenesis and tumor metastasis through binding
      to the extracellular matrix.

PMID- 9614123
TI  - Precise timing of expression of a Plasmodium falciparum-derived transgene in
      Plasmodium berghei is a critical determinant of subsequent subcellular
      localization.
AB  - The development of transfection technology for malaria parasites holds
      significant promise for a more detailed characterization of molecules targeted by
      vaccines or drugs. One asexual blood stage vaccine candidate, apical membrane
      antigen-1 (AMA-1) of merozoite rhoptries has been shown to be the target of
      inhibitory, protective antibodies in both in vitro and in vivo studies. We have
      investigated heterologous (trans-species) expression of the human malaria
      Plasmodium falciparum AMA-1 (PF83/AMA-1) in the rodent parasite Plasmodium
      berghei. Transfected P. berghei expressed correctly folded and processed PF83/AMA
      1 under control of both pb66/ama-1 and dhfr-ts promoters. Timing of expression
      was highly promoter-dependent and was critical for subsequent subcellular
      localization. Under control of pb66/ama-1, PF83/AMA-1 expression and localization
      in P. berghei was limited to the rhoptries of mature schizonts, similar to that
      observed for PF83/AMA-1 in P. falciparum. In contrast the dhfr-ts promoter
      permitted PF83/AMA-1 expression throughout schizogony as well as in gametocytes
      and gametes. Localization was aberrant and included direct expression at the
      merozoite and gamete surface. Processing from the full-length 83-kDa protein to a
      66-kDa protein was observed not only in schizonts but also in gametocytes,
      indicating that processing could be mediated outside of rhoptries by a common
      protease. Trans-species expressed PF83/AMA-1 was highly immunogenic in mice,
      resulting in a response against a functionally critical domain of the molecule.

PMID- 9614125
TI  - Functional properties of the neuronal nicotinic acetylcholine receptor beta3
      promoter in the developing central nervous system.
AB  - Within the chick central nervous system, expression of the beta3 nicotinic
      acetylcholine receptor gene is restricted to a subset of retinal neurons, the
      majority of which are ganglion cells. Transient transfection in retinal neurons
      and in neural and non-neural cells from other regions of the chick embryo allowed
      the identification of the cis-regulatory domain of the beta3 gene. Within this
      domain, a 75-base pair fragment located immediately upstream of the transcription
      start site suffices to reproduce the neuron-specific expression pattern of beta3.
      This fragment encompasses an E-box and a CAAT box, both of which are shown to be
      key positive regulatory elements of the beta3 promoter. Co-transfection
      experiments into retinal, telencephalic, and tectal neurons with plasmid
      reporters of beta3 promoter activity and a number of vectors expressing different
      neuronal (ASH-1, NeuroM, NeuroD, CTF-4) and non-neuronal (MyoD) basic helix-loop
      helix transcription factors indicate that the cis-regulatory domain of beta3 has
      the remarkable property of discriminating accurately between related members of
      the basic helix-loop-helix protein family. The sequence located immediately 3' of
      the E-box participates in this selection, and the E-box acts in concert with the
      nearby CAAT box.

PMID- 9614126
TI  - The structure of the beta-propeller domain and C-terminal region of the integrin
      alphaM subunit. Dependence on beta subunit association and prediction of domains.
AB  - The alphaM subunit of integrin Mac-1 contains several distinct regions in its
      extracellular segment. The N-terminal region has been predicted to fold into a
      beta-propeller domain composed of seven beta-sheets each about 60 amino acid
      residues long, with the I-domain inserted between beta-sheets 2 and 3. The
      structure of the C-terminal region is unknown. We have used monoclonal antibodies
      (mAbs) as probes to study the dependence of the structure of different regions of
      the alphaM subunit on association with the beta2 subunit in the alphaM/beta2
      heterodimer. All of the mAbs to the I-domain immunoprecipitated the unassociated
      alphaM precursor and reacted with the alphaM subunit expressed alone on the
      surface of COS cells. By contrast, four mAbs to the beta-propeller domain did not
      react with the unassociated alphaM precursor nor with the uncomplexed alphaM
      subunit expressed on COS cell surface. The four mAbs were mapped to three
      subregions in three different beta-sheets, making it unlikely that each
      recognized an interface between the alpha and beta subunits. These results
      suggest that folding of different beta-propeller subregions is coordinate and is
      dependent on association with the beta2 subunit. The segment C-terminal to the
      beta-propeller domain, residues 599-1092, was studied with nine mAbs. A subset of
      four mAbs that reacted with the alphaM/beta2 complex but not with the
      unassociated alphaM subunit were mapped to one subregion, residues 718-759, and
      five other mAbs that recognized both the unassociated and the complexed alphaM
      subunit were localized to three other subregions, residues 599-679, 820-882, and
      943-1047. This suggests that much of the region C-terminal to the beta-propeller
      domain folds independently of association with the beta2 subunit. Our data
      provide new insights into how different domains in the integrin alpha and beta
      subunits may interact.

PMID- 9614127
TI  - Multiple NF-kappaB enhancer elements regulate cytokine induction of the human
      inducible nitric oxide synthase gene.
AB  - The human inducible nitric oxide synthase (iNOS) gene is overexpressed in a
      number of human inflammatory diseases. Previously, we observed that the human
      iNOS gene is transcriptionally regulated by cytokines and demonstrated that the
      cytokine-responsive regions are upstream of -3.8 kilobase pairs (kb). Therefore,
      the purpose of this study was to further localize the functional enhancer
      elements and to assess the role of the transcription factor NF-kappaB in both
      human liver (AKN-1) and human lung (A549) epithelial cell lines. The addition of
      NF-kappaB inhibitors significantly suppressed cytokine-stimulated iNOS mRNA
      expression and NO synthesis, indicating that NF-kappaB is involved in the
      induction of the human iNOS gene. Analysis of the first 4.7 kb of the 5'-flanking
      region demonstrated basal promoter activity and failed to show any cytokine
      inducible activity. However, promoter constructs extending to -5.8 and -7.2 kb
      revealed 2-3-fold and 4-5-fold induction, respectively, in the presence of
      cytokines. DNA sequence analysis from -3.8 to -7.2 kb identified five putative NF
      kappaB cis-regulatory transcription factor binding sites upstream of -4.7 kb.
      Site-directed mutagenesis of these sites revealed that the NF-kappaB motif at 
      5.8 kb is required for cytokine-induced promoter activity, while the sites at 
      5.2, -5.5, and -6.1 kb elicit a cooperative effect. Electromobility shift assays
      using a site-specific oligonucleotide and nuclear extracts from cells stimulated
      with cytokine-mixture, tumor necrosis factor-alpha or interleukin-1beta, but not
      interferon-gamma, exhibited inducible DNA binding activity for NF-kappaB. These
      data indicate that NF-kappaB activation is required for cytokine induction of the
      human iNOS gene and identifies four NF-kappaB enhancer elements upstream in the
      human iNOS promoter that confer inducibility to tumor necrosis factor-alpha and
      interleukin-1beta.

PMID- 9614128
TI  - Disruption of Escherichia coli hepA, an RNA polymerase-associated protein, causes
      UV sensitivity.
AB  - During the development of purification procedures for Escherichia coli RNA
      polymerase (RNAP), we noticed the consistent co-purification of a 110-kDa
      polypeptide. Here, we report the identification of the 110-kDa protein as the
      product of the hepA gene, a member of the SNF2 family of putative helicases. We
      have cloned the hepA gene and overexpressed and purified the HepA protein. We
      show in vitro that RNAP preparations have an ATPase activity only in the presence
      of HepA and that HepA binds core RNAP competitively with the promoter specificity
      sigma70 subunit with a 1:1 stoichiometry and a dissociation constant (Kd) of 75
      nM. An E. coli strain with a disruption in the hepA gene shows sensitivity to
      ultraviolet light.

PMID- 9614129
TI  - The b and delta subunits of the Escherichia coli ATP synthase interact via
      residues in their C-terminal regions.
AB  - An affinity resin for the F1 sector of the Escherichia coli ATP synthase was
      prepared by coupling the b subunit to a solid support through a unique cysteine
      residue in the N-terminal leader. b24-156, a form of b lacking the N-terminal
      transmembrane domain, was able to compete with the affinity resin for binding of
      F1. Truncated forms of b24-156, in which one or four residues from the C terminus
      were removed, competed poorly for F1 binding, suggesting that these residues play
      an important role in b-F1 interactions. Sedimentation velocity analytical
      ultracentrifugation revealed that removal of these C-terminal residues from b24
      156 resulted in a disruption of its association with the purified delta subunit
      of the enzyme. To determine whether these residues interact directly with delta,
      cysteine residues were introduced at various C-terminal positions of b and
      modified with the heterobifunctional cross-linker benzophenone-4-maleimide. Cross
      links between b and delta were obtained when the reagent was incorporated at
      positions 155 and 158 (two residues beyond the normal C terminus) in both the
      reconstituted b24-156-F1 complex and the membrane-bound F1F0 complex. CNBr
      digestion followed by peptide sequencing showed the site of cross-linking within
      the 177-residue delta subunit to be C-terminal to residue 148, possibly at Met
      158. These results indicate that the b and delta subunits interact via their C
      terminal regions and that this interaction is instrumental in the binding of the
      F1 sector to the b subunit of F0.

PMID- 9614130
TI  - Role of the constitutive splicing factors U2AF65 and SAP49 in suboptimal RNA
      splicing of novel retroviral mutants.
AB  - Retroviruses display a unique form of alternative splicing in which both spliced
      and unspliced RNAs accumulate in the cytoplasm. Simple retroviruses, such as
      avian sarcoma virus, do not encode regulatory proteins that affect splicing; this
      process is controlled solely through interactions between the viral RNA and the
      host cell splicing machinery. Previously, we described the selection and
      characterization of novel avian sarcoma virus mutants. These viruses were
      separated into two classes based upon analysis of splicing intermediates produced
      in infected cells and in a cell-free system. One class, which included mutants
      with altered polypyrimidine tract or branch point sequences, showed significant
      accumulation of intermediates, suggesting that splicing was regulated in step 2.
      The other class, which included mutants with deletions of exonic enhancer
      sequences, did not accumulate splicing intermediates, suggesting that splicing
      was regulated before step 1 of the splicing reaction. In this report, we show
      that a mutant blocked at step 1 fails to form a stable spliceosomal complex,
      whereas one blocked at step 2 shows a defect in its ability to transit through
      the last spliceosomal complex. Using UV cross-linking methods, we show that
      regulation at each step is associated with specific changes in the binding of
      cellular splicing factors. Regulation at step 1 is correlated with decreased
      cross-linking of the factor U2AF65, whereas regulation at step 2 is correlated
      with enhanced cross-linking of the factor SAP49. Because these mutations were
      isolated by selection for replication-competent viruses, we conclude that
      retroviral splicing may be regulated in vivo through altered binding of
      constitutive splicing factors.

PMID- 9614131
TI  - Membrane topology of an ATP-gated ion channel (P2X receptor).
AB  - Western blots of Xenopus oocyte membrane preparations showed that the apparent
      molecular mass of the wild type P2X2 receptor (about 65 kDa) was reduced by
      pretreatment with endoglycosidase H. Mutagenesis of one or more of three
      potential asparagines (N182S, N239S, and N298S) followed by Western blots showed
      that each of the sites was glycosylated in the wild type receptor. Functional
      channels were formed by receptors lacking any single asparagine, but not by
      channels mutated in two or three positions. Artificial consensus sequences (N-X
      S/T) introduced into the N-terminal region (asparagine at position 9, 16, or 26)
      were not glycosylated. Asparagines were glycosylated when introduced at the C
      terminal end of the first hydrophobic domain (positions 62 and 66) and at the N
      terminal end of the second hydrophobic domain (position 324). A protein in which
      the C terminus of one P2X2 subunit was joined to the N terminus of a second P2X2
      subunit (from a concatenated cDNA) had twice the molecular mass of the P2X2
      receptor subunit, and formed fully functional channels. The experiments provide
      direct evidence for the topology originally proposed for the P2X receptor, with
      intracellular N and C termini, two membrane-spanning domains, and a large
      extracellular loop.

PMID- 9614132
TI  - Effect of acidic pH on the structure and lipid binding properties of porcine
      surfactant protein A. Potential role of acidification along its exocytic pathway.
AB  - Pulmonary surfactant protein A (SP-A) is synthesized by type II cells and stored
      intracellularly in secretory granules (lamellar bodies) together with surfactant
      lipids and hydrophobic surfactant proteins B and C (SP-B and SP-C). We asked
      whether the progressive decrease in pH along the exocytic pathway could influence
      the secondary structure and lipid binding and aggregation properties of porcine
      SP-A. Conformational analysis from CD spectra of SP-A at various pH values
      indicated that the percentage of alpha-helix progressively decreased and that of
      beta-sheet increased as the pH was reduced. The protein underwent a marked self
      aggregation at mildly acidic pH in the presence of Ca2+, conditions thought to
      resemble those existing in the trans-Golgi network. Protein aggregation was
      greater as the pH was reduced. We also found that both neutral and acidic
      vesicles either with or without SP-B or SP-C bound to SP-A at acidic pH as
      demonstrated by co-migration during centrifugation. However, the binding of
      acidic but not neutral vesicles to SP-A led to 1) a striking change in the CD
      spectra of the protein, which was interpreted as a decrease of the level of SP-A
      self-aggregation, and 2) a protection of the protein from endoproteinase Glu-C
      degradation at pH 4.5. SP-A massively aggregated acidic vesicles but poorly
      aggregated neutral vesicles at acidic pH. Aggregation of
      dipalmitoylphosphatidylcholine (DPPC) vesicles either with or without SP-B and/or
      SP-C strongly depended on pH, being progressively decreased as the pH was reduced
      and markedly increased when pH was shifted back to 7.0. At the pH of lamellar
      bodies, SP-A-induced aggregation of DPPC vesicles containing SP-B or a mixture of
      SP-B and SP-C was very low, although SP-A bound to these vesicles. These results
      indicate that 1) DPPC binding and DPPC aggregation are different phenomena that
      probably have different SP-A structural requirements and 2) aggregation of
      membranes induced by SP-A at acidic pH is critically dependent on the presence of
      acidic phospholipids, which affect protein structure, probably preventing the
      formation of large aggregates of protein.

PMID- 9614133
TI  - Co-expression of a Ca2+-inhibitable adenylyl cyclase and of a Ca2+-sensing
      receptor in the cortical thick ascending limb cell of the rat kidney. Inhibition
      of hormone-dependent cAMP accumulation by extracellular Ca2+.
AB  - The Ca2+-sensing receptor protein and the Ca2+-inhibitable type 6 adenylyl
      cyclase mRNA are present in a defined segment of the rat renal tubule leading to
      the hypothesis of their possible functional co-expression in a same cell and thus
      to a possible inhibition of cAMP content by extracellular Ca2+. By using
      microdissected segments, we compared the properties of regulation of
      extracellular Ca2+-mediated activation of Ca2+ receptor to those elicited by
      prostaglandin E2 and angiotensin II. The three agents inhibited a common pool of
      hormone-stimulated cAMP content by different mechanisms as follows. (i)
      Extracellular Ca2+, coupled to phospholipase C activation via a pertussis toxin
      insensitive G protein, induced a dose-dependent inhibition of cAMP content (1.25
      mM Ca2+ eliciting 50% inhibition) resulting from both stimulation of cAMP
      hydrolysis and inhibition of cAMP synthesis; this latter effect was mediated by
      capacitive Ca2+ influx as well as release of intracellular Ca2+. (ii) Angiotensin
      II, coupled to the same transduction pathway, also decreased cAMP content;
      however, its inhibitory effect on cAMP was mainly accounted for by an increase of
      cAMP hydrolysis, although angiotensin II and extracellular Ca2+ can induce
      comparable release of intracellular Ca2+. (iii) Prostaglandin E2, coupled to
      pertussis toxin-sensitive G protein, inhibited the same pool of adenylyl cyclase
      units as extracellular Ca2+ but by a different mechanism. The functional
      properties of the adenylyl cyclase were similar to those described for type 6.
      The results establish that the co-expression of a Ca2+-inhibitable adenylyl
      cyclase and of a Ca2+-sensing receptor in a same cell allows an inhibition of
      cAMP accumulation by physiological concentrations of extracellular Ca2+.

PMID- 9614134
TI  - A putative heterotrimeric G protein inhibits the fusion of COPI-coated vesicles.
      Segregation of heterotrimeric G proteins from COPI-coated vesicles.
AB  - Heterotrimeric G proteins have been implicated in the regulation of intracellular
      protein transport, but their mechanism of action remains unclear. In vivo,
      secretion of chromogranin B, tagged with the green fluorescent protein, was
      inhibited by the addition of a general activator of trimeric G proteins (AlF4-)
      to stably transfected Vero cells and resulted in an accumulation of the tagged
      protein in the Golgi apparatus. In an in vitro assay that reconstitutes intra
      Golgi protein transport, we find that a membrane-bound and AlF4--sensitive factor
      is involved in the fusion reaction. To determine whether this effect is mediated
      by a heterotrimeric G protein localized to COPI-coated transport vesicles, we
      determined the presence of G proteins on these vesicles and found that they were
      segregated relative to the donor membranes. Because G proteins do not have an
      obvious sorting, retention, or retrieval signal, we considered the possibility
      that other interactions might be responsible for this segregation. In agreement
      with this, we found that trimeric G proteins from isolated Golgi membranes were
      partially insoluble in Triton X-100. Identification of the proteins that interact
      with the heterotrimeric G proteins in the Golgi-derived detergent-insoluble
      complex might help to reveal the regulation of protein secretion mediated by
      heterotrimeric G proteins.

PMID- 9614135
TI  - MHC class I heavy chain mRNA must exceed a threshold level for the reconstitution
      of cell surface expression of class I MHC complexes in cells transformed by the
      highly oncogenic adenovirus 12.
AB  - In primary embryonal fibroblasts from transgenic mice expressing H-2(b) genes and
      a miniature swine class I transgene (PD1), transformation with adenovirus 12
      results in suppression of assembly and cell surface expression of all class I
      complexes. Cell surface expression of PD1 can be recovered by transfecting the
      cells with peptide transporter genes. However, reconstitution of the H-2Kb gene
      expression requires, in addition, a 2-fold increase in the steady state level of
      the H-2Kb mRNA that can be attained by treatment of the cells with interferons or
      by transfecting them with the H-2Kb gene. A detailed analyses of the biogenesis
      of class I molecules has revealed the steady state expression of free class I
      heavy chains that are not converted into conformed complexes even when peptide
      transporter genes are overexpressed. The fact that class I complex assembly seems
      to be highly inefficient in certain cell lines might be a major in vivo obstacle
      for the elimination of transformed or virus-infected cells by cytotoxic T
      lymphocytes, especially in view of the fact that the level of class I gene
      transcription is often down-regulated in cancer cells and/or that assembly of
      class I major histocompatibility complexes can be subverted by virus-encoded
      proteins.

PMID- 9614136
TI  - MEF-2 and Oct-1 bind to two homologous promoter sequence elements and participate
      in the expression of a skeletal muscle-specific gene.
AB  - The murine adult IIB myosin heavy chain (IIB MyHC) gene is expressed only in
      certain skeletal muscle fibers. Within the proximal promoter are two A + T-rich
      motifs, mAT1 and mAT2, which greatly enhance muscle-specific transcription;
      myogenic cells contain proteins that bind to these sequences. MEF-2 binds to both
      mAT1 and mAT2; a mutation abolishing its binding to mAT1 greatly diminishes the
      activity of the promoter. Both mAT motifs also form complexes with a protein
      requiring a target sequence typical of POU domain proteins, which migrate in
      electrophoretic mobility shift assays to the same position as a complex
      containing purified Oct-1 and which are supershifted by an antibody specific to
      Oct-1; this protein is therefore probably Oct-1. Footprinting experiments
      demonstrate that mAT1 is preferentially occupied by MEF-2 and mAT2 by Oct-1 and
      that these two proteins appear to bind cooperatively to their respective sites.
      Although the two mAT motifs have sequences that are very similar, they
      nonetheless exhibit distinct behaviors and perform differently in the activation
      of the promoter. The contribution of the IIB MyHC gene to specification of the
      myogenic phenotype is thus at least in part regulated by MEF-2 and Oct-1.

PMID- 9614137
TI  - Active participation of Hsp90 in the biogenesis of the trimeric reovirus cell
      attachment protein sigma1.
AB  - The reovirus cell attachment protein, sigma1, is a lollipop-shaped homotrimer
      with an N-terminal fibrous tail and a C-terminal globular head. Biogenesis of
      this protein involves two trimerization events: N-terminal trimerization, which
      occurs cotranslationally and is Hsp70/ATP-independent, and C-terminal
      trimerization, which occurs posttranslationally and is Hsp70/ATP-dependent. To
      determine if Hsp90 also plays a role in sigma1 biogenesis, we analyzed sigma1
      synthesized in rabbit reticulocyte lysate. Coprecipitation experiments using anti
      Hsp90 antibodies revealed that Hsp90 was associated with immature sigma1 trimers
      (hydra-like intermediates with assembled N termini and unassembled C termini) but
      not with mature trimers. The use of truncated sigma1 further demonstrated that
      only the C-terminal half of sigma1 associated with Hsp90. In the presence of the
      Hsp90 binding drug geldanamycin, N-terminal trimerization proceeded normally, but
      C-terminal trimerization was blocked. Geldanamycin did not inhibit the
      association of Hsp90 with sigma 1 but prevented the subsequent release of Hsp90
      from the immature sigma1 complex. We also examined the status of p23, an Hsp90
      associated cochaperone. Like Hsp90, p23 only associated with immature sigma1
      trimers, and this association was mapped to the C-terminal half of sigma1.
      However, unlike Hsp90, p23 was released from the sigma1 complex upon the addition
      of geldanamycin. These results highlight an all-or-none concept of chaperone
      involvement in different oligomerization domains within a single protein and
      suggest a possible common usage of chaperones in the regulation of general
      protein folding and of steroid receptor activation.

PMID- 9614138
TI  - beta1D integrin inhibits cell cycle progression in normal myoblasts and
      fibroblasts.
AB  - Integrins are alphabeta heterodimeric transmembrane receptors involved in the
      regulation of cell growth and differentiation. The beta1 integrin subunit is
      widely expressed in vivo and is represented by four alternatively spliced
      cytoplasmic domain isoforms. beta1D is a muscle-specific variant of beta1
      integrin and a predominant beta1 isoform in striated muscles. In the present
      study we showed that expression of the exogenous beta1D integrin in C2C12
      myoblasts and NIH 3T3 or REF 52 fibroblasts inhibited cell proliferation. Unlike
      the case of the common beta1A isoform, adhesion of beta1D-transfected C2C12
      myoblasts specifically via the expressed integrin did not activate mitogen
      activated protein kinases. The beta1D-induced growth inhibitory signal was shown
      to occur late in the G1 phase of the cell cycle, before the G1-S transition. Ha
      (12R)Ras, but not (Delta22W)Raf-1 oncogene, was able to overcome completely the
      beta1D-triggered cell growth arrest in NIH 3T3 fibroblasts. Since perturbation of
      the beta1D amino acid sequence in beta1A/beta1D chimeric integrins decreased the
      growth inhibitory signal, the entire cytoplasmic domain of beta1D appeared to be
      important for this function. However, an interleukin-2 receptor-beta1D chimera
      containing the cytoplasmic domain of beta1D still efficiently inhibited cell
      growth, showing that the ectodomain and the ligand-binding site in beta1D were
      not required for the growth inhibitory signal. Together, our data showed a new
      specific function for the alternatively spliced beta1D integrin isoform. Since
      the onset of beta1D expression during myodifferentiation coincides with the
      timing of myoblast withdrawal from the cell cycle, the growth inhibitory
      properties of beta1D demonstrated in this study might reflect the major function
      for this integrin in commitment of differentiating skeletal muscle cells in vivo.

PMID- 9614139
TI  - SR-BII, an isoform of the scavenger receptor BI containing an alternate
      cytoplasmic tail, mediates lipid transfer between high density lipoprotein and
      cells.
AB  - The scavenger receptor class B, type I (SR-BI), binds high density lipoprotein
      (HDL) and mediates selective uptake of cholesteryl ester from HDL and HDL
      dependent cholesterol efflux from cells. We recently identified a new mRNA
      variant that differs from the previously characterized form in that the encoded C
      terminal cytoplasmic domain is almost completely different. In the present study,
      we demonstrate that the mRNAs for mouse SR-BI and SR-BII (previously termed SR
      BI.2) are the alternatively spliced products of a single gene. The translation
      products predicted from human, bovine, mouse, hamster, and rat cDNAs exhibit a
      high degree of sequence similarity within the SR-BII C-terminal domain (62-67%
      identity when compared with the human sequence), suggesting that this variant is
      biologically important. SR-BII protein represents approximately 12% of the total
      immunodetectable SR-BI/II protein in mouse liver. Subcellular fractionation of
      transfected Chinese hamster ovary cells showed that SR-BII, like SR-BI, is
      enriched in caveolae, indicating that the altered cytoplasmic tail does not
      affect targeting of the receptor. SR-BII mediated both selective cellular uptake
      of cholesteryl ether from HDL as well as HDL-dependent cholesterol efflux from
      cells, although with approximately 4-fold lower efficiency than SR-BI. In vivo
      studies using adenoviral vectors showed that SR-BII was relatively less efficient
      than SR-BI in reducing plasma HDL cholesterol. These studies show that SR-BII, an
      HDL receptor isoform containing a distinctly different cytoplasmic tail, mediates
      selective lipid transfer between HDL and cells, but with a lower efficiency than
      the previously characterized variant.

PMID- 9614140
TI  - Multiple signal transduction pathways link Na+/K+-ATPase to growth-related genes
      in cardiac myocytes. The roles of Ras and mitogen-activated protein kinases.
AB  - We showed before that in neonatal rat cardiac myocytes partial inhibition of
      Na+/K+-ATPase by nontoxic concentrations of ouabain causes hypertrophic growth
      and transcriptional regulations of genes that are markers of cardiac hypertrophy.
      In view of the suggested roles of Ras and p42/44 mitogen-activated protein
      kinases (MAPKs) as key mediators of cardiac hypertrophy, the aim of this work was
      to explore their roles in ouabain-initiated signal pathways regulating four
      growth-related genes of these myocytes, i.e. those for c-Fos, skeletal alpha
      actin, atrial natriuretic factor, and the alpha3-subunit of Na+/K+-ATPase.
      Ouabain caused rapid activations of Ras and p42/44 MAPKs; the latter was
      sustained longer than 90 min. Using high efficiency adenoviral-mediated
      expression of a dominant-negative Ras mutant, and a specific inhibitor of MAPK
      kinase (MEK), activation of Ras-Raf-MEK-p42/44 MAPK cascade by ouabain was shown.
      The effects of the mutant Ras, an inhibitor of Ras farnesylation, and the MEK
      inhibitor on ouabain-induced changes in mRNAs of the four genes indicated that
      (a) skeletal alpha-actin induction was dependent on Ras but not on p42/44 MAPKs,
      (b) alpha3 repression was dependent on the Ras-p42/44 MAPK cascade, and (c)
      induction of c-fos or atrial natriuretic factor gene occurred partly through the
      Ras-p42/44 MAPK cascade, and partly through pathways independent of Ras and
      p42/44 MAPKs. All ouabain effects required extracellular Ca2+, and were
      attenuated by a Ca2+/calmodulin antagonist or a protein kinase C inhibitor. The
      findings show that (a) signal pathways linked to sarcolemmal Na+/K+-ATPase share
      early segments involving Ca2+ and protein kinase C, but diverge into multiple
      branches only some of which involve Ras, or p42/44 MAPKs, or both; and (b) there
      are significant differences between this network and the related gene regulatory
      pathways activated by other hypertrophic stimuli, including those whose responses
      involve increases in intracellular free Ca2+ through different mechanisms.

PMID- 9614141
TI  - Carbon monoxide and nitric oxide suppress the hypoxic induction of vascular
      endothelial growth factor gene via the 5' enhancer.
AB  - Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis
      and blood vessel remodeling. Its expression is up-regulated in vascular smooth
      muscle cells by a number of conditions, including hypoxia. Hypoxia increases the
      transcriptional rate of VEGF via a 28-base pair enhancer located in the 5'
      upstream region of the gene. The gas molecules nitric oxide (NO) and carbon
      monoxide (CO) are important vasodilating agents. We report here that these
      biological molecules can suppress the hypoxia-induced production of VEGF mRNA and
      protein in smooth muscle cells. In transient expression studies, both NO and CO
      inhibited the ability of the hypoxic enhancer we have previously identified to
      activate gene transcription. Furthermore, electrophoretic mobility shift assays
      indicated decreased binding of hypoxia-inducible factor 1 (HIF-1) to this
      enhancer by nuclear proteins isolated from CO-treated cells, although HIF-1
      protein levels were unaffected by CO. Given that both CO and NO activate guanylyl
      cyclase to produce cGMP and that a cGMP analog (8-Br-cGMP) showed a similar
      suppressive effect on the hypoxic induction of the VEGF enhancer, we speculate
      that the suppression of VEGF by these two gas molecules occurs via a cyclic GMP
      mediated pathway.

PMID- 9614142
TI  - Human DNA polymerase beta deoxyribose phosphate lyase. Substrate specificity and
      catalytic mechanism.
AB  - DNA polymerase beta (beta-pol) cleaves the sugar-phosphate bond 3' to an intact
      apurinic/apyrimidinic (AP) site (i.e. AP lyase activity). The same bond is
      cleaved even if the AP site has been previously 5'-incised by AP endonuclease,
      resulting in a 5' 2-deoxyribose 5-phosphate (i.e. dRP lyase activity). We
      characterized these lyase reactions by steady-state kinetics with the amino
      terminal 8-kDa domain of beta-pol and with the entire 39-kDa polymerase. Steady
      state kinetic analyses show that the Michaelis constants for both the dRP and AP
      lyase activities of beta-pol are similar. However, kcat is approximately 200-fold
      lower for the AP lyase activity on an intact AP site than for an AP endonuclease
      preincised site. The 8-kDa domain was also less efficient with an intact AP site
      than on a preincised site. The full-length enzyme and the 8-kDa domain
      efficiently remove the 5' dRP from a preincised AP site in the absence of Mg2+,
      and the pH profiles of beta-pol and 8-kDa domain dRP lyase catalytic efficiency
      exhibit a broad alkaline pH optimum. An inhibitory effect of pyridoxal 5'
      phosphate on the dRP lyase activity is consistent with involvement of a primary
      amine (Lys72) as the Schiff base nucleophile during lyase chemistry.

PMID- 9614143
TI  - Regulation of alphaIIb beta3 function in human B lymphocytes.
AB  - We studied the function of the platelet integrin alphaIIb beta3 using a B
      lymphocyte model in which alphaIIb beta3 can be induced to interact with
      fibrinogen using phorbol myristate acetate (PMA). To determine whether a G
      protein-coupled receptor could also activate alphaIIb beta3 in lymphocytes, we
      coexpressed the human formyl peptide receptor (fPR) and alphaIIb beta3, finding
      that the fPR agonist formyl Met-Leu-Phe (fMLP)-stimulated lymphocyte adherence to
      immobilized fibrinogen and binding of soluble fibrinogen to the lymphocyte
      surface. The response to fMLP, but not PMA, was abrogated by pertussis toxin,
      indicating that the fPR was coupled to the G-protein Galphai, whereas the protein
      kinase C inhibitor bisindolylmaleimide I inhibited the response to both fMLP and
      PMA, indicating that signaling from the fPR included protein kinase C. On the
      other hand, the tyrosine kinase inhibitor genistein, the Syk inhibitor
      piceatannol, and the RhoA inhibitor C3 exoenzyme had no effect, implying that
      neither tyrosine phosphorylation nor the GTPase RhoA were involved. Furthermore,
      whereas micromolar concentrations of cytochalasin D inhibited the PMA-stimulated
      interaction of alphaIIb beta3 with fibrinogen, nanomolar concentrations actually
      induced fibrinogen binding to unstimulated cells. Our studies demonstrate that
      alphaIIb beta3 expressed in B lymphocytes can be activated by a physiologic
      agonist and outline an activating pathway that includes Galphai, protein kinase
      C, and the actin cytoskeleton.

PMID- 9614144
TI  - Nucleosome assembly activity and intracellular localization of human CAF-1
      changes during the cell division cycle.
AB  - We characterized changes of nucleosome assembly activity, intracellular
      localization, and reversible phosphorylation of the human chromatin assembly
      factor CAF-1 during the somatic cell division cycle. HeLa cells were synchronized
      in the G1, S, G2, and M phases of the cell cycle. All three subunits of human CAF
      1 (p150, p60, and p48) are present during the entire cell cycle. In interphase,
      p150 and p60 are bound to the nucleus, but they predominantly dissociate from
      chromatin during mitosis. During S phase, p150 and p60 are concentrated at sites
      of intranuclear DNA replication. Only a fraction of total p48 is associated with
      p150 and p60, and the majority is present in other high molecular weight
      complexes. The other nucleosome assembly protein, NAP-1, is predominantly
      cytosolic throughout the cell cycle. Human CAF-1 efficiently mediates nucleosome
      assembly during complementary DNA strand synthesis in G1, S, and G2 phase
      cytosolic extracts. Active CAF-1 can be isolated as a 6.5 S complex from G1, S,
      and G2 phase nuclei. In contrast, CAF-1 isolated from mitotic cytosol does not
      support nucleosome assembly during DNA synthesis. In mitosis, the p60 subunit of
      inactive CAF-1 is hyperphosphorylated, whereas active CAF-1 in interphase
      contains hypophosphorylated and/or phosphorylated forms of p60.

PMID- 9614145
TI  - Synthetic processing of surfactant protein C by alevolar epithelial cells. The
      COOH terminus of proSP-C is required for post-translational targeting and
      proteolysis.
AB  - Surfactant protein C (SP-C) is synthesized by alveolar type II cells as a 21-kDa
      propeptide (proSP-C21) which is proteolytically processed in subcellular
      compartments distal to the trans-Golgi network to yield a 35-residue mature form.
      Initial synthetic processing events for SP-C include post-translational cleavages
      of the COOH terminus of proSP-C21 yielding two intermediates (16 and 6 kDa). To
      test the role of specific COOH-terminal domains in intracellular targeting and
      proteolysis of proSP-C21, synthesis and processing of SP-C was evaluated using a
      lung epithelial cell line (A549) transfected with a eukaryotic expression vector
      containing either the full-length cDNA for rat SP-C (SP-Cwt) or one of six
      polymerase chain reaction (PCR)-generated COOH terminally truncated forms (SP-C1
      185, SP-C1-175, SP-C1-147, SP-C1-120, SP-C1-72, and SP-C1-59). Using in vitro
      transcription/translation, each of the seven constructs produced a 35S-labeled
      product of appropriate length which could be immunoprecipitated by epitope
      specific proSP-C antisera. Immunoprecipitation of 35S-labeled A549 cell lysates
      from SP-Cwt transfectants demonstrated rapid synthesis of [35S]proSP-C21 with
      processing to SP-C16 and SP-C6 intermediates via cleavages of the COOH-terminal
      propeptide. Both the intermediates as well as the kinetics of processing in A549
      cells were similar to that observed in rat type II cells. In contrast, constructs
      SP-C1-185, SP-C1-175, SP-C1-147, SP-C1-120, SP-C1-72, and SP-C1-59 were each
      translated but degraded without evidence of proteolytic processing. Fluorescence
      immunocytochemistry identified proSP-Cwt in cytoplasmic vesicles of A549 cells
      while all COOH-terminal deletional mutants were restricted to an endoplasmic
      reticulum/Golgi compartment identified by co-localization with fluorescein
      isothiocyanate-concanavalin A. We conclude that SP-Cwt expressed in A549 cells is
      directed to cytoplasmic vesicles where it is proteolytically processed in a
      manner similar to native type II cells and that amino acids Cys186-Ile194 located
      at the COOH terminus of proSP-C21 are necessary for correct intracellular
      targeting and subsequent cleavage events.

PMID- 9614146
TI  - Interleukin-1beta-induced rat pancreatic islet nitric oxide synthesis requires
      both the p38 and extracellular signal-regulated kinase 1/2 mitogen-activated
      protein kinases.
AB  - Interleukin-1beta (IL-1beta) is cytotoxic to rat pancreatic beta-cells by
      inhibiting glucose oxidation, causing DNA damage and inducing apoptosis. Nitric
      oxide (NO) is a necessary but not sufficient mediator of these effects. IL-1beta
      induced kinase activity toward Elk-1, activation transcription factor 2, c-Jun,
      and heat shock protein 25 in rat islets. By Western blotting with phosphospecific
      antibodies and by immunocomplex kinase assay, IL-1beta was shown to activate
      extracellular signal-regulated kinase (ERK) 1/2 and p38 mitogen-activated protein
      kinase (p38) in islets and rat insulinoma cells. Specific ERK1/2 and p38
      inhibitors individually reduced but in combination blocked IL-1beta-mediated
      islet NO synthesis, and reverse transcription-polymerase chain reaction of
      inducible NO synthase mRNA showed that ERK1/2 and p38 controlled IL-1beta-induced
      islet inducible NO synthase expression at the transcriptional level.
      Hyperosmolarity caused phosphorylation of Elk-1, activation transcription factor
      2, and heat shock protein 25 and activation of ERK1/2 and p38 in islets
      comparable to that induced by IL-1beta but did not lead to NO synthesis.
      Inhibition of p38 but not of ERK1/2 attenuated IL-1beta-mediated inhibition of
      glucose-stimulated insulin release. We conclude that ERK1/2 and p38 activation is
      necessary but not sufficient for IL-1beta-mediated beta-cell NO synthesis and
      that p38 is involved in signaling of NO-independent effects of IL-1beta in beta
      cells.

PMID- 9614148
TI  - Polyunsaturated fatty acid regulation of gene expression.
AB  - For the past three decades, polyunsaturated fatty acids (PUFA) have been
      recognized as important energy sources and membrane components. PUFA also play
      key roles in many cellular events, such as gene regulation. Most recently,
      research has focused on identifying the mechanisms by which PUFA modulate gene
      transcription, mRNA stability and cellular differentiation. It is the purpose of
      this review to examine the effects of PUFA on gene expression in lipogenic as
      well as other tissues. Because the (n-3) and (n-6) series of PUFA are intimately
      involved in gene regulation, they will be the focus of review. The effects of
      other fatty acid families on gene expression are reviewed elsewhere.

PMID- 9614147
TI  - Double-stranded RNA-induced inducible nitric-oxide synthase expression and
      interleukin-1 release by murine macrophages requires NF-kappaB activation.
AB  - The effects of double-stranded RNA (synthetic polyinosinic-polycytidylic acid;
      poly(I-C)) on macrophage expression of inducible nitric-oxide synthase (iNOS),
      production of nitric oxide, and release of interleukin-1 (IL-1) were
      investigated. Individually, poly(I-C), interferon-gamma (IFN-gamma), and
      lipopolysaccharide (LPS) stimulate nitrite production and iNOS expression by RAW
      264.7 cells. In combination, the effects of poly(I-C) + IFN-gamma are additive,
      while poly(I-C) does not further potentiate LPS-induced nitrite production. These
      results suggest that poly(I-C) and LPS may stimulate iNOS expression by similar
      signaling pathways, which may be independent of pathways activated by IFN-gamma.
      LPS-induced iNOS expression is associated with the activation of NF-kappaB. We
      show that inhibition of NF-kappaB by pyrrolidinedithiocarbamate prevents poly(I
      C) + IFN-gamma-, poly(I-C) + LPS-, and LPS-induced iNOS expression, nitrite
      production and IkappaB degradation by RAW 264.7 cells. The effects of poly(I-C)
      on iNOS expression appear to be cell-type specific. Poly(I-C), alone or in
      combination with IFN-gamma, does not stimulate, nor does poly(I-C) potentiate, IL
      1-induced nitrite production by rat insulinoma RINm5F cells. In addition, we show
      that the combination of poly(I-C) + IFN-gamma stimulates iNOS expression, nitrite
      production, IkappaB degradation, and the release of IL-1 by primary mouse
      macrophages, and these effects are prevented by pyrrolidinedithiocarbamate. These
      findings indicate that double-stranded RNA, in the presence of IFN-gamma, is a
      potent activator of macrophages, stimulating iNOS expression, nitrite production,
      and IL-1 release by a mechanism which requires the activation of NF-kappaB.

PMID- 9614149
TI  - Moderate dietary protein and energy restriction modulate cAMP-dependent protein
      kinase activity in rat liver.
AB  - Very low protein diets result in a desensitization of hepatic cAMP signaling in
      rats, which is characterized by a loss of cAMP-dependent protein kinase (PKA)
      activity and type I regulatory subunit (RI). Here we have tested whether more
      moderate protein restriction (Trial 1) or energy restriction (Trial 2) also
      modulates hepatic PKA quantity and activity. In trial 1, weanling rats were
      allowed free access to diets containing normal protein (15%, AL-NP), moderately
      restricted protein (12.5%, AL-MP) and low protein (7.5%, AL-LP); in trial 2, rats
      were allowed free access to diet containing 15% (AL-NP) or 0.5% protein (very low
      protein, AL-VLP) or were energy restricted by pair-feeding a diet isonitrogenous
      to AL-NP but at 65% of the energy intake (ER-IN) for 14 d. Body weights were
      lower (P < 0.05) by d 14 in all restricted groups compared with the AL-NP group.
      The quantity of cytosolic RI was lower (P < 0.05) in AL-LP and AL-VLP, but not in
      AL-MP or ER-IN, compared with AL-NP. In contrast, there was no effect of diet on
      RI in the particulate fraction. RII was not changed by moderate and low protein
      diets in either the cytosol or particulate fraction. However, type II regulatory
      subunit (RII) was greater in the cytosol of ER-IN and in the particulate fraction
      of AL-VLP (P < 0.05) compared with AL-NP. Specific activity of PKA was lower in
      the cytosol and particulate fraction (P < 0.05) in the AL-VLP and ER-IN groups
      compared with the AL-NP group. In contrast, specific activity of PKA was
      maintained in cytosol from AL-LP, but lower in the particulate fraction (P <
      0.05) compared with AL-NP. In summary, protein restricted-diets lower RI subunit
      in the cytosol; however, only in rats fed very low protein diets is this loss of
      RI associated with lower cytosolic PKA activity. In contrast, energy restriction
      lowers PKA activity in the cytosol and particulate fractions, independent of
      signficant reduction in RI or RII subunits. Taken together, these data indicate
      that moderate protein and energy restrictions have differential effects on
      activity and quantity of PKA.

PMID- 9614150
TI  - Dietary fructooligosaccharides change the concentration of calbindin-D9k
      differently in the mucosa of the small and large intestine of rats.
AB  - Previously, we confirmed that dietary fructooligosaccharides (FOS) increase
      calcium absorption in rats. In this study, we examined the influence of FOS
      feeding on the concentration of calbindin-D9k of several intestinal segments in
      rats. Rats in the control group were fed a diet without FOS. Rats in the other
      two groups were fed the diet containing FOS at either 50 or 100 g/kg for 10 d and
      subjected to a calcium absorption study. On the final day of feeding, the rats
      were killed and the entire intestine was removed. The intestinal mucosa was
      collected from four segments, i.e., the proximal and distal segments of the small
      intestine, the cecum and the colorectum, respectively. The apparent absorption of
      calcium increased dose dependently (r = 0.9256, P < 0.0001). Significant positive
      correlations between apparent calcium absorption and the relative amounts of
      calbindin in both large intestinal segments were observed (cecum, r = 0.8956, P =
      0.0011; colorectum, r = 0.8828, P = 0.0016). Also, significant negative
      correlations between apparent calcium absorption and the relative amounts of
      calbindin-D9k in both small intestinal segments were observed (proximal, r = 
      0.7149, P = 0. 0304; distal, r = -0.8740, P = 0.0021). In conclusion, FOS feeding
      increases levels of calbindin-D9k in the large intestine, but decreases those in
      the small intestine. Moreover, these results suggest that part of the stimulatory
      effect of fructooligosaccharides relates to the transcellular route of calcium
      absorption in the large intestine of rats.

PMID- 9614151
TI  - Mechanisms of decreased lipoprotein lipase activity in adipocytes of starved rats
      depend on duration of starvation.
AB  - The aim of this study was to delineate the mechanisms by which varying periods of
      starvation decrease lipoprotein lipase (LPL) activity in rat adipose tissue. LPL
      mRNA levels and rates of LPL synthesis, degradation and secretion were compared
      in adipocytes from male rats that had been fed or starved for 1 or 3 d. The
      decreased LPL activity after 3 d of starvation (-76%) was explained mainly by a
      50% decrease in the relative abundance of LPL mRNA levels (P < 0.05) and a
      parallel 50% decrease in relative rates of LPL biosynthesis (P < 0.05). In
      contrast, starvation for 1 d decreased total LPL activity by 47% (P < 0.05) but
      did not affect LPL mRNA levels or relative rates of LPL biosynthesis. Pulse-chase
      studies demonstrated that 1 d of starvation increased the rate of degradation of
      newly synthesized LPL (P < 0.05) and markedly decreased its secretion into the
      medium (P < 0.05). A decrease in overall protein synthesis also contributed to
      the decreased LPL activity after 1 and 3 d of starvation. We conclude that the
      relative importance of pre- and post-translational mechanisms in regulating
      adipose tissue LPL activity depends on the duration of starvation. During short
      term starvation, degradation of newly synthesized LPL is an important determinant
      to its secretion from the adipocyte and hence its functional activity at the
      capillary endothelium.

PMID- 9614152
TI  - Weaning and the weanling diet influence the villous height and crypt depth in the
      small intestine of pigs and alter the concentrations of short-chain fatty acids
      in the large intestine and blood.
AB  - Effects of weaning pigs to different diets have been investigated in terms of the
      changes in the small intestinal morphology, and in the absorption of short-chain
      fatty acids (SCFA) and sodium from the large intestine. One piglet from each of
      six litters containing nine pigs was sampled on the day of weaning; the other
      eight piglets were divided into four equal groups and fed different diets as
      follows: unweaned, weanling diet, or sow's milk at high or low level. Four and
      seven days after weaning, measurements of the intestinal tissue and contents were
      made; the plasma concentrations of SCFA, aldosterone and sodium were also
      measured. The villous height in the small intestine was highest in the unweaned
      group and greater in the high milk group than in either the weanling diet or low
      milk group (P < 0.001). Apparently, villous atrophy was due more to the level of
      feed intake than to the composition of the diet. The concentrations of SCFA in
      the large intestine and portal blood were highest in the weanling diet group and
      lowest in the low milk group. The low milk group tended to have higher blood
      concentrations of aldosterone (P = 0.15), which may have compensated for the low
      concentrations of SCFA in maintaining a higher percentage of dry matter in the
      intestine. Pigs fed weanling diet may use the energy from the SCFA to maintain a
      body weight comparable to that of pigs fed milk at a low level.

PMID- 9614153
TI  - Dietary isoflavones reduce plasma cholesterol and atherosclerosis in C57BL/6 mice
      but not LDL receptor-deficient mice.
AB  - Susceptibility to atherosclerosis is determined by a combination of genetic and
      environmental factors, including diet. Consumption of diets rich in soy protein
      has been claimed to protect against the development of atherosclerosis. Potential
      mechanisms include cholesterol lowering, inhibition of lipoprotein oxidation and
      inhibition of cell proliferation by soy proteins or isoflavones, such as
      genistein, that are present in soy. This study was designed to determine whether
      soy isoflavones confer protection against atherosclerosis in mice and whether
      they reduce serum cholesterol levels and lipoprotein oxidation. C57BL/6 and LDL
      receptor-deficient (LDLr-null) mice were fed soy protein-based, high fat diets
      with isoflavones present (IF+, 20.85 g/100 g protein, 0.027 g/100 g genistein,
      0.009 g/100 g daidzein) or diets from which isoflavones, and possibly other
      components, had been extracted (IF-, 20.0 g/100 g protein, 0.002 g/100 g
      genistein, 0.001 g/100 g daidzein). Because LDLr-null mice develop extensive
      atherosclerosis and hypercholesterolemia after minimal time on a high fat diet,
      they were fed the diets for 6 wk, whereas C57BL/6 mice were fed the diets for 10
      wk. Plasma cholesterol levels did not differ between LDLr-null mice fed IF- and
      those fed IF+, but were 30% lower in C57BL/6 mice fed the IF+ diet than in those
      fed the IF- diet. Susceptibility of LDL to oxidative modification, measured as
      the lag phase of conjugated diene formation in LDLr-null mice, was not altered by
      isoflavone consumption. All LDLr-null mice developed atherosclerosis, and the
      presence or deficiency of dietary isoflavones did not influence atherosclerotic
      lesion area. In contrast, atherosclerotic lesion area was significantly reduced
      in C57BL/6 mice fed IF+ compared with those fed IF-. Thus, this study
      demonstrates that although the isoflavone-containing diet resulted in a reduction
      in cholesterol levels in C57BL/6 mice, it had no effect on cholesterol levels or
      on susceptibility of LDL to oxidative modification in LDLr-null mice. Further,
      dietary isoflavones did not protect against the development of atherosclerosis in
      LDLr-null mice but did decrease atherosclerosis in C57BL/6 mice. These findings
      suggest that soy isoflavones might lower cholesterol levels by increasing LDL
      receptor activity, and the reduction in cholesterol may offer some protection
      against atherosclerosis.

PMID- 9614154
TI  - Acute inflammation induces hyporetinemia and modifies the plasma and tissue
      response to vitamin A supplementation in marginally vitamin A-deficient rats.
AB  - Plasma retinol is reduced during numerous infections, and inflammation alters the
      hepatic synthesis of retinol-binding protein (RBP). In this study, we have
      investigated the effects of endotoxin-induced inflammation on vitamin A (VA)
      supplementation in a rat model of marginal VA deficiency. Marginally VA-deficient
      rats received an intraperitoneal dose of lipopolysaccharide (LPS, n = 14) or
      saline (n = 10); 6 h later, six LPS + VA and six saline + VA rats received 7.1
      micromol VA orally. Twenty-four hours after endotoxin administration, rats with
      inflammation (LPS) had lower plasma retinol, RBP, and hepatic RBP than saline
      rats (37, 31 and 44%, respectively, P < 0.05). Inflammation did not affect VA
      concentrations in liver and perirenal adipose tissue, although kidney VA was
      reduced relative to saline rats. However, urinary VA was not detected. Eighteen
      hours after VA supplementation, inflammation reduced the plasma unesterified
      retinol response (P < 0. 05) in LPS + VA relative to saline + VA rats, although
      total VA increased as a result of the presence of retinyl esters in LPS + VA
      rats. Hepatic esterified retinol concentration was reduced (P < 0. 01) in LPS +
      VA compared with saline + VA rats; however, hepatic unesterified retinol did not
      differ. Renal total retinol increased in VA-supplemented rats, but urinary
      retinol excretion, when observed, was low, independently of inflammation. These
      findings indicate that inflammation-induced hyporetinemia does not necessarily
      imply a loss of VA, but rather represents a redistribution of tissue VA brought
      about by a reduced hepatic synthesis of RBP. Practical implications from these
      collective results are to recommend the determination of both unesterified and
      esterified retinol to fully assess the plasma response to VA supplementation and
      to caution the use of VA assessment methodologies that depend on the hepatic
      synthesis of RBP during acute inflammation.

PMID- 9614155
TI  - Lipogenic enzyme gene expression is quickly suppressed in rats by a small amount
      of exogenous polyunsaturated fatty acids.
AB  - An examination was conducted of the time courses of incorporation of
      polyunsaturated fatty acids (PUFA) into lipids of plasma, liver and its nuclei,
      and the time courses of hepatic lipogenic enzyme gene expression after oral
      administration of perilla oil by a stomach tube to rats fed a fat-free diet.
      Linolenic acid, 18:3(n-3), and eicosapentaenoic acid, 20:5(n-3), were considered
      indices of exogenous fatty acids. In total lipids of liver and its nuclei,
      linolenic acid was detected 1 h after the intubation, continued to increase
      during the first 4 h, then decreased and almost disappeared by 48 h.
      Eicosapentaenoic acid also increased within only 1 h of intubation, reached a
      maximum after 8 h and then gradually decreased. In contrast with the increase of
      exogenous PUFA, the mRNA concentrations of hepatic lipogenic enzymes began to
      decrease 2 h after the perilla oil intubation, were at a minimum at 8 h, and then
      increased. In another experiment to examine the effects of dietary perilla oil
      concentration on PUFA incorporation and gene expression, rats were given diets
      containing 0-10% perilla oil (supplemented with hydrogenated fat to 10% fat) for
      3 d. Only 1% perilla oil elevated the exogenous PUFA concentrations in liver and
      its nuclei in comparison with concentrations in rats fed a hydrogenated fat diet.
      Perilla oil at 2% of the diet was sufficient to suppress lipogenic enzyme gene
      expressions, which were suppressed to the minimum level by 5% perilla oil in the
      diet. Thus, lipogenic enzyme gene expression was quickly suppressed by a small
      amount of exogenous PUFA, in contrast with the increase of PUFA incorporation
      into liver and its nuclei. Newly incorporated exogenous PUFA appear to be
      involved in suppression of lipogenic enzyme gene expression.

PMID- 9614156
TI  - Histidine availability alters glucagon gene expression in murine alphaTC6 cells.
AB  - Because individual amino acids (AA) stimulate glucagon release from pancreatic
      alpha-cells, the purpose of this study was to determine if individual AA could
      influence glucagon gene expression. Preproglucagon mRNA levels were 67% lower (P
      < 0.05) in mouse alphaTC6 cells incubated for 12 h in amino acid-free medium
      compared with cells incubated in complete medium containing all 20 AA. A time
      course study indicated that alphaTC6 cells incubated in amino acid-free medium +/
      1 micromol/L puromycin or amino acid-containing medium plus puromycin exhibited
      similar preproglucagon mRNA decreases over 12 h. When 1 micromol/L actinomycin
      was added to medium with or without AA, ppG mRNA concentrations decreased (P <
      0.05) for 3h; however, values at 12 h were not different than those at 3 h.
      Deletions of single AA from complete medium demonstrated that only histidine
      removal or depletion reproduced the decrease in ppG mRNA observed in amino acid
      free medium. We conclude that histidine is involved in the regulation of
      preproglucagon mRNA levels in alphaTC6 cells and that this regulation may be
      operative during both transcriptional and post-transcriptional events.

PMID- 9614157
TI  - Digestion of carbohydrate from white beans (Phaseolus vulgaris L.) in healthy
      humans.
AB  - Resistant starch (RS) is thought to be present in large amounts in legume seeds;
      however, it has never been quantified in healthy humans. RS from cooked
      (atmospheric pressure) white beans was quantified in humans and pigs, and
      characterized to explain its low digestibility. Six human volunteers were
      intubated to collect ileal digesta after an experimental meal composed of orange
      juice, butter and 167 g beans (dry matter basis). The reliability of the
      intubation method was examined in a pig study in which it was compared with
      another collection method, ileal cannulation. Chemical analyses, microscopy and
      size exclusion chromatography were performed on human and pig digesta. The pig
      study showed that the intubation method may underestimate the quantity of RS.
      However, no chemical/physical difference was observed between the RS collected by
      the two techniques. In the human study, 16.5 +/- 1.3% (11.3 g) of the ingested
      starch was recovered as RS. The microscopy of the digesta showed that part of the
      RS was enclosed in the cell walls. Although the RS was composed mainly of alpha
      glucan molecules with a degree of polymerization (DP) 40 to 60, oligosaccharides
      and large molecules of DP > 400 were also present. Retrogradation was not found
      to be the main factor responsible for starch malabsorption. We conclude that
      white beans may contain a large amount of RS formed mainly by partially degraded
      molecules protected by the cell walls during their transit through the gut.

PMID- 9614158
TI  - Metabolizable energy of high non-starch polysaccharide-maintenance and weight
      reducing diets in men: experimental appraisal of assessment systems.
AB  - We have examined the reliability of several food energy assessment systems for
      healthy men. The predictions of metabolizable energies were compared with
      determinations made in energy balance studies with three maintenance diets (12
      MJ/d); one of the diets was moderate in non-starch polysaccharide (NSP; 2.1% of
      gross energy) and two were higher in NSP (3.5-4.6% of gross energy). A fourth
      diet was a submaintenance (6 MJ/d) high NSP (7% gross energy) diet. Discrepancies
      between the different food energy assessment systems and the determined
      metabolizable energy values ranged between 0 and 15%. With the maintenance diets,
      the Atwater specific factor system had errors generally within 6% of the
      determined value and a limit of agreement (bias +2SD) for diets of 10%. This
      accuracy compares with errors of 2% for both the originally published assessment
      of this system and a more recent general formula; both systems were without bias
      with increasing NSP content of the diets but the latter had limits of agreement
      within 3%. In contrast, the Atwater general, the European general and a recent
      FDA general formula showed increasing bias with increasing NSP intake. All of the
      general energy assessment systems overpredicted metabolizable energy from the
      high NSP submaintenance diet, which shows that even the least biased and most
      reliable energy assessment system that we identified applies to maintenance diets
      only; thus a correction has to be made for submaintenance diets.

PMID- 9614159
TI  - Consumption of exogenous bifidobacteria does not alter fecal bifidobacteria and
      breath hydrogen excretion in humans.
AB  - The hypothesis that consumption of bifidobacteria by humans would increase
      colonic bifidobacteria and decrease breath hydrogen excretion was examined. A
      commercially available strain of bifidobacteria was tracked through the
      gastrointestinal tract. We determined that a 12-d feeding period of 10(10) cells
      of exogenous bifidobacteria daily was adequate to achieve a stable number of
      exogenous bifidobacteria in the colon. A 12-d washout period was chosen because
      the exogenous bifidobacteria could no longer be detected at that time. A double
      blind crossover study used both male and female subjects. The order of treatment
      with skim milk alone or skim milk + bifidobacteria was randomized. Breath
      hydrogen excretion (micromol/L) and fecal counts of total bifidobacteria [log
      colony forming units (CFU)/g feces] were not significantly different between
      males and females and were not affected by consumption of exogenous
      bifidobacteria. Calculations based on the numbers of exogenous bifidobacteria
      consumed and the fecal numbers of exogenous bifidobacteria excreted suggested
      that numbers of the exogenous strain increased within the gastrointestinal tract.
      These data suggest that it is difficult to permanently alter total colonic
      bifidobacteria and affect physiologic function (net hydrogen in the colon as
      reflected by breath hydrogen) by feeding bifidobacteria, although the percentage
      of the total bifidobacteria represented by the exogenous strain can be affected.

PMID- 9614160
TI  - Alcohol-free red wine enhances plasma antioxidant capacity in humans.
AB  - Moderate wine consumption is reputed to exert a protective effect against
      coronary heart disease (CHD). The nature of the protective compounds is unclear
      and the mechanisms are incompletely understood. We studied whether the
      nonalcoholic component of wine increases plasma antioxidant capacity measured as
      total radical-trapping antioxidant parameter (TRAP), and whether such an effect
      is associated with the presence of phenolic compounds in plasma. The TRAP and
      plasma levels of phenolic compounds were measured in 10 healthy subjects after
      the ingestion of 113 mL of tap water (control) and alcohol-free red and white
      wine at 1-wk intervals. Both alcohol-free wines possessed an in vitro dose
      dependent peroxyl-radical activity, but red wine, with a polyphenol concentration
      of 363 +/- 48.0 mg/L quercetin equivalent (QE), was 20 times more active (40.0 +/
      0.1 mmol/L) than white wine (1.9 +/- 0.1 mmol/L), which has a polyphenol
      concentration of 31 +/- 1 mg QE/L. The ingestion of alcohol-free red wine caused
      significant increases in plasma TRAP values and polyphenol concentrations 50 min
      after ingestion. Alcohol-free white wine and water had no effects on either of
      the plasma values. The parallel and prompt increase of antioxidant status and of
      circulating levels of polyphenols in fasting subjects after bolus ingestion of a
      moderate amount of alcohol-free red wine suggests that polyphenols are absorbed
      in the upper gastrointestinal tract and might be directly involved in the in vivo
      antioxidant defenses.

PMID- 9614161
TI  - Fraction of carbon-free body mass as oxygen is a constant body composition ratio
      in men.
AB  - Although elements are the foundation of the human body, information concerning
      the atomic level of body composition is still limited. The aim of this study was
      to explore potentially constant relationships among elements found in vivo. Based
      on the known stoichiometries of relevant chemical components, a theoretical model
      was derived, suggesting the existence of a relatively constant ratio of total
      body oxygen to carbon-free body mass (TBO/CFM) in men. Eight elements (C, H, N,
      Ca, P, K, Na and Cl ) were measured in 22 healthy male subjects by using in vivo
      neutron activation-40K whole-body counting, and TBO was calculated as the
      difference between body mass and the sum of the eight measured elements. TBO (in
      kg) was significantly correlated with CFM (in kg): TBO = 0.829 x CFM - 1.8; r =
      0.998, P < 0.001, standard error of estimate = 0.4 kg. The ratio of TBO to CFM
      was relatively constant, mean +/- SD at 0. 800 +/- 0.009 with a CV of 1.1%.
      Oxygen and carbon are the two most abundant elements in the human body. The
      discovery of a constant relationship between oxygen and carbon is not only
      helpful for understanding the atomic level of body composition, but also provides
      the possibility of estimating the content of specific elements in vivo.

PMID- 9614162
TI  - Dietary structured triacylglycerols containing docosahexaenoic acid given from
      birth affect visual and auditory performance and tissue fatty acid profiles of
      rats.
AB  - To examine whether it is possible to enhance the level of 22:6(n-3) in the
      central nervous system, newborn rats were fed dietary supplements containing oils
      with either specific or random triacylglycerol structure, but similar
      concentrations of polyunsaturated fatty acids. In the specific structured oil,
      22:6(n-3) was located in the sn-2 position, whereas it was equally distributed
      among the three positions in the triacylglycerol molecule in the randomized oil.
      A reference group was fed rat milk before weaning and nonpurified diet after
      weaning. After 12 wk, the levels of 22:6(n-3) in brain and liver phospholipids
      were higher in the groups fed the experimental diets than in the reference group.
      The specific structured oil resulted in the highest level of 22:6(n-3) in the
      brain, whereas the level of 22:6(n-3) was highest in the liver of the group fed
      randomized oil, indicating differences in metabolism of fatty acids resulting
      from their position in the dietary triacylglycerol molecule. The higher levels of
      22:6(n-3) were accompanied by significantly lower levels of the long-chain (n-6)
      polyunsaturated fatty acids compared with the reference group. The fatty acid
      profiles, including the level of 22:6(n-3), in the retina phospholipids were not
      affected by the three different diets apart from a lower level of 20:4(n-6) in
      rats fed the experimental diets, indicating a strong tendency to maintain a high
      level of 22:6(n-3) in the retina. The changes in the fatty acid profiles did not
      result in differences in learning ability, but caused changes in visual function,
      evidenced by higher latency of the b-wave and lower oscillatory potential, and in
      auditory brainstem response, evidenced by generally greater amplitude of wave Ia
      in the group fed specific structured oil.

PMID- 9614163
TI  - Sesamolin inhibits lipid peroxidation in rat liver and kidney.
AB  - Although the sesame lignans, sesaminol and sesamolinol, have been shown to
      possess antioxidative activity, less is known about the metabolism and
      antioxidative properties of sesamolin, a major constituent of sesame oil. To
      determine the ability of sesamolin to act as an antioxidant in vivo, we fed rats
      a diet containing 1% sesamolin for 2 wk and studied its metabolism and its
      effects on oxidative stress. About 75% of the ingested sesamolin was excreted
      unmetabolized in feces, but it was not detected in urine. Sesamolin and its
      metabolites, sesamol and sesamolinol, were excreted primarily as sulfates and
      glucuronides. The amount of sesamolin and its metabolites was lower in the plasma
      than in the liver or kidneys. When we compared rats fed a diet containing 1%
      sesamolin for 14 d with those fed a control diet, we found that liver weight was
      significantly greater in the former group. Lipid peroxidation activity, measured
      as 2-thiobarbituric acid reactive substances, was significantly lower in the
      kidneys and liver of the sesamolin-fed rats than in the controls. In addition,
      the amount of 8-hydroxy-2'-deoxyguanosine excreted in the urine was significantly
      lower in the sesamolin-fed rats. These results suggest that sesamolin and its
      metabolites may contribute to the antioxidative properties of sesame seeds and
      oil and support our hypothesis that sesame lignans reduce susceptibility to
      oxidative stress.

PMID- 9614164
TI  - Insulin-dependent glucose utilization in intensively milk-fed veal calves is
      modulated by supplemental lactose in an age-dependent manner.
AB  - Postprandial insulin resistance with excessive hyperinsulinemia, hyperglycemia
      and glucosuria develops with increasing age in veal calves intensively fed milk
      replacers. We tested the age dependency of insulin resistance, modulated by high
      lactose intake, glucose oxidation and insulin receptor number and affinity after
      an overnight period without food. Male calves were fed a milk replacer containing
      290 or 423 g lactose and 310 and 541 g total sugar/kg from 69-195 kg body weight.
      At mean body weights of 95 and 170 kg, insulin-dependent glucose metabolism was
      studied in euglycemic-hyperinsulinemic glucose clamps (EGC), and glucose
      dependent insulin responses were tested in hyperglycemic clamps (HGC). EGC were
      combined with infusions of [13C6]glucose to measure glucose kinetics and glucose
      oxidation by determination of 13CO2 exhalation. During EGC and HGC, insulin
      concentrations were similar in both groups, indicating comparable insulin
      secretion and metabolic clearance rates. On the basis of glucose infusion rates
      required to maintain eu- or hyperglycemia in EGC and HGC, respectively, insulin
      dependent glucose utilization was not age dependent. However, in calves receiving
      a high lactose intake, insulin-dependent glucose utilization was enhanced in the
      early phases, but was reduced in the late stages of the growth trial. Insulin
      dependent glucose utilization behaved inversely with atom % excess of
      [13C6]glucose, but changed in a manner similar to that of the rate of glucose
      appearance. Inhibition of endogenous glucose output, exhalation of 13CO2 and
      amounts of oxidized glucose exhibited no group differences. More glucose was
      therefore stored in lactose-supplemented calves. A reduced insulin receptor
      number in skeletal muscle in calves fed high amounts of lactose likely
      contributed to low insulin-dependent glucose utilization.

PMID- 9614165
TI  - Alimentary lipemia is enhanced in fiber-fed rats.
AB  - The effect of dietary fiber on the pattern of postprandial lipemia was examined
      in two studies with male Wistar rats. In the first study, groups of rats were
      killed after food deprivation (0 h) or 1, 4.5 or 8.5 h after a high fat test meal
      containing either cellulose (CL) or oat bran (OB). Plasma triglycerides (TG) were
      higher in the OB group at 4.5 h compared with both the 0-h and the CL-groups at
      4. 5 h. In both groups, LDL and TG-rich lipoprotein cholesterol (TRL-C)
      concentrations were higher at 8.5 h than at 0 h; HDL cholesterol was
      significantly lower at 8.5 h than at 0 h for the OB group only. The enhanced
      lipemia when OB was fed may stimulate cholesterol movement from HDL to LDL and
      TRL. To examine whether TRL secretion rates were responsible for the enhanced
      lipemia, a second study was conducted. Rats were fitted with jugular catheters
      and allowed to recover. Two groups were fed either CL or OB and infused with
      Triton-1339 (400 mg/kg). Two control groups were not fed and were infused with
      either Triton or saline. Rats were killed 2.5 h after infusion. Plasma TG was 10
      fold higher in the Triton group than in the saline group, but did not differ
      between the OB and CL groups. The relative contribution of TRL-C to total
      cholesterol was significantly greater in the Triton control than in the OB and CL
      groups. Enhanced secretion of TRL was not responsible for the lipemia observed in
      the first study. Rather, alterations in clearance rate were responsible.

PMID- 9614166
TI  - Placental copper transport in rats: effects of elevated dietary zinc on fetal
      copper, iron and metallothionein.
AB  - We hypothesized that the competition between zinc (Zn) and copper (Cu) during
      fetal accretion of copper could be discriminated at either the dam-to-placenta or
      placenta-to-fetus stage. This premise was tested by feeding dams a high Zn diet
      (1000 mg/kg, HZn) during the second half of gestation. One day before delivery,
      dams were anesthetized, fetuses removed and both maternal and fetal tissues and
      plasma obtained and assayed. Other rats were fed a normal Zn concentration diet
      (32.4 mg/kg, ND) throughout pregnancy. There were significantly lower fetal liver
      Cu concentrations and greater plasma Fe concentrations, but not plasma Cu
      concentrations or liver Fe concentrations in the HZn group. Both dam and fetal Zn
      liver concentrations were greater in the HZn than in the ND group. Plasma Cu
      levels were lower in the HZn-fed than in the ND-fed dams. Placental tissue from
      the HZn litters had a greater concentration of Zn and Fe than did the ND group,
      whereas no effect was noted for Cu concentration. Metallothionein (MT) levels
      were elevated in dam livers and placenta in the HZn group, but there were no
      differences in fetal liver MT. The dynamic assessment of placental transport was
      conducted by injecting 2.5 mg/kg Cu acetate intravenously into dams of both
      groups. Sequential samplings of dam and fetal blood and placentas were taken from
      0 to 60 min. After the Cu bolus, there was a consistently higher plasma Cu
      concentration in the HZn than in the ND dams, but no alteration in the
      concentration of Cu in the placenta or fetal plasma. This study indicates that
      placental Cu uptake is not affected by a high Zn diet in the dam. In addition,
      the greater Zn concentration in the placenta of HZn than in ND litters results in
      abnormal fetal Cu, Fe and Zn concentrations, suggesting that an imbalanced
      maternal mineral consumption is deleterious to normal divalent metal accretion.

PMID- 9614167
TI  - Nutritional utilization by rats of chickpea (Cicer arietinum) meal and its
      isolated globulin proteins is poorer than that of defatted soybean or
      lactalbumin.
AB  - The effects on performance, digestibility, N utilization and plasma amino acid
      concentrations of dietary chickpea (Cicer arietinum, var. Kabuli) seed meal,
      globulin proteins or buffer-insoluble residue [starch + non-starch
      polysaccharides (NSP) + lignin] were studied in growing rats. Chickpea meal,
      defatted soybean meal, chickpea globulins and lactalbumin were each incorporated
      into diets as the sole source of dietary protein (100 g/kg). In addition,
      chickpea insoluble residue was included in a control diet in the same proportion
      found in the chickpea meal. Rats were killed while under halothane anesthesia
      after 10 d of consuming the diets, and ileal contents were washed out and freeze
      dried for digestibility measurements. Weight gains and gain:feed ratios of rats
      fed chickpea diets for 10 d did not differ from those of rats fed defatted
      soybean but were significantly lower than those of rats given the control
      (lactalbumin) diet. However, ileal and fecal N digestibilities and N retention by
      rats fed the chickpea diet were significantly lower than those obtained with the
      lactalbumin or soybean diet. The inclusion of both chickpea meal or its globulin
      proteins in the diet significantly increased the amount of N excreted, primarily
      as urea, through the urine. However, although ileal N digestibility values for
      chickpea meal were significantly lower, those for its constituent globulins did
      not differ from control values. Urea levels in plasma in rats fed diets
      containing chickpea meal, globulins or soybean meal were significantly higher
      than in those fed lactalbumin. Furthermore, the concentrations of glycine,
      phenylalanine, histidine, arginine and ornithine in the plasma of rats fed
      chickpea meal, its globulins or defatted soybean were significantly higher,
      whereas those of threonine, leucine, lysine and tryptophan were significantly
      lower than lactalbumin-fed controls. The chickpea insoluble residue had no
      adverse effects on performance or N utilization by rats. We conclude that the low
      nutritional value of chickpea meal is likely to be due mainly to adverse effects
      of its globulin proteins on growth and N metabolism rather than to the action of
      any known antinutritional factor present in the diet.

PMID- 9614168
TI  - Does excess dietary protein adversely affect bone? Symposium overview.

PMID- 9614169
TI  - Excess dietary protein can adversely affect bone.
AB  - The average American diet, which is high in protein and low in fruits and
      vegetables, generates a large amount of acid, mainly as sulfates and phosphates.
      The kidneys respond to this dietary acid challenge with net acid excretion, as
      well as ammonium and titratable acid excretion. Concurrently, the skeleton
      supplies buffer by active resorption of bone. Indeed, calciuria is directly
      related to net acid excretion. Different food proteins differ greatly in their
      potential acid load, and therefore in their acidogenic effect. A diet high in
      acid-ash proteins causes excessive calcium loss because of its acidogenic
      content. The addition of exogenous buffers, as chemical salts or as fruits and
      vegetables, to a high protein diet results in a less acid urine, a reduction in
      net acid excretion, reduced ammonium and titratable acid excretion, and decreased
      calciuria. Bone resorption may be halted, and bone accretion may actually occur.
      Alkali buffers, whether chemical salts or dietary fruits and vegetables high in
      potassium, reverse acid-induced obligatory urinary calcium loss. We conclude that
      excessive dietary protein from foods with high potential renal acid load
      adversely affects bone, unless buffered by the consumption of alkali-rich foods
      or supplements.

PMID- 9614170
TI  - Excess dietary protein may not adversely affect bone.
AB  - Too little protein is always harmful for the skeleton. Increasing dietary protein
      increases endogenous calcium excretion. The ability to adapt depends upon the
      adequacy of an individual's calcium intake. At a population level, the effect of
      protein is often minimized because calcium intake rises with increasing protein
      intake. A dietary calcium-to-protein ratio >/=20:1 (mg:g) probably provides
      adequate protection for the skeleton. Excess protein will not harm the skeleton
      if the calcium intake is adequate.

PMID- 9614171
TI  - The Caenorhabditis elegans unc-64 locus encodes a syntaxin that interacts
      genetically with synaptobrevin.
AB  - We describe the molecular cloning and characterization of the unc-64 locus of
      Caenorhabditis elegans. unc-64 expresses three transcripts, each encoding a
      molecule with 63-64% identity to human syntaxin 1A, a membrane- anchored protein
      involved in synaptic vesicle fusion. Interestingly, the alternative forms of
      syntaxin differ only in their C-terminal hydrophobic membrane anchors. The forms
      are differentially expressed in neuronal and secretory tissues; genetic evidence
      suggests that these forms are not functionally equivalent. A complete loss-of
      function mutation in unc-64 results in a worm that completes embryogenesis, but
      arrests development shortly thereafter as a paralyzed L1 larva, presumably as a
      consequence of neuronal dysfunction. The severity of the neuronal phenotypes of
      C. elegans syntaxin mutants appears comparable to those of Drosophila syntaxin
      mutants. However, nematode syntaxin appears not to be required for embryonic
      development, for secretion of cuticle from the hypodermis, or for the function of
      muscle, in contrast to Drosophila syntaxin, which appears to be required in all
      cells. Less severe viable unc-64 mutants exhibit a variety of behavioral defects
      and show strong resistance to the acetylcholinesterase inhibitor aldicarb.
      Extracellular physiological recordings from pharyngeal muscle of hypomorphic
      mutants show alterations in the kinetics of transmitter release. The lesions in
      the hypomorphic alleles map to the hydrophobic face of the H3 coiled-coil domain
      of syntaxin, a domain that in vitro mediates physical interactions with similar
      coiled-coil domains in SNAP-25 and synaptobrevin. Furthermore, the unc-64
      syntaxin mutants exhibit allele-specific genetic interactions with mutants
      carrying lesions in the coiled-coil domain of synaptobrevin, providing in vivo
      evidence for the significance of these domains in regulating synaptic vesicle
      fusion.

PMID- 9614172
TI  - Nitrogen-regulated ubiquitination of the Gap1 permease of Saccharomyces
      cerevisiae.
AB  - Addition of ammonium ions to yeast cells growing on proline as the sole nitrogen
      source induces rapid inactivation and degradation of the general amino acid
      permease Gap1 through a process requiring the Npi1/Rsp5 ubiquitin (Ub) ligase. In
      this study, we show that NH4+ induces endocytosis of Gap1, which is then
      delivered into the vacuole where it is degraded. This down-regulation is
      accompanied by increased conversion of Gap1 to ubiquitinated forms.
      Ubiquitination and subsequent degradation of Gap1 are impaired in the npi1
      strain. In this mutant, the amount of Npi1/Rsp5 Ub ligase is reduced >10-fold
      compared with wild-type cells. The C-terminal tail of Gap1 contains sequences,
      including a di-leucine motif, which are required for NH4+-induced internalization
      and degradation of the permease. We show here that mutant Gap1 permeases affected
      in these sequences still bind Ub. Furthermore, we provide evidence that only a
      small fraction of Gap1 is modified by Ub after addition of NH4+ to mutants
      defective in endocytosis.

PMID- 9614173
TI  - Immunoisolation and characterization of a subdomain of the endoplasmic reticulum
      that concentrates proteins involved in COPII vesicle biogenesis.
AB  - Rubella virus E1 glycoprotein normally complexes with E2 in the endoplasmic
      reticulum (ER) to form a heterodimer that is transported to and retained in the
      Golgi complex. In a previous study, we showed that in the absence of E2,
      unassembled E1 subunits accumulate in a tubular pre-Golgi compartment whose
      morphology and biochemical properties are distinct from both rough ER and Golgi.
      We hypothesized that this compartment corresponds to hypertrophied ER exit sites
      that have expanded in response to overexpression of E1. In the present study we
      constructed BHK cells stably expressing E1 protein containing a cytoplasmically
      disposed epitope and isolated the pre-Golgi compartment from these cells by cell
      fractionation and immunoisolation. Double label indirect immunofluorescence in
      cells and immunoblotting of immunoisolated tubular networks revealed that
      proteins involved in formation of ER-derived transport vesicles, namely p58/ERGIC
      53, Sec23p, and Sec13p, were concentrated in the E1-containing pre-Golgi
      compartment. Furthermore, budding structures were evident in these membrane
      profiles, and a highly abundant but unknown 65-kDa protein was also present. By
      comparison, marker proteins of the rough ER, Golgi, and COPI vesicles were not
      enriched in these membranes. These results demonstrate that the composition of
      the tubular networks corresponds to that expected of ER exit sites. Accordingly,
      we propose the name SEREC (smooth ER exit compartment) for this structure.

PMID- 9614174
TI  - B-50/GAP-43-induced formation of filopodia depends on Rho-GTPase.
AB  - In the present study we show that expression of the neural PKC-substrate B-50
      (growth-associated protein [GAP-43]) in Rat-1 fibroblasts induced the formation
      of filopodial extensions during spreading. This morphological change was
      accompanied by an enhanced formation of peripheral actin filaments and by
      accumulation of vinculin immunoreactivity in filopodial focal adhesions,
      colocalizing with B-50. In time lapse experiments, the B-50-induced filopodial
      extensions were shown to stay in close contact with the substratum and appeared
      remarkably stable, resulting in a delayed lamellar spreading of the fibroblasts.
      The morphogenetic effects of the B-50 protein were entirely dependent on the
      integrity of the two N-terminal cysteines involved in membrane association
      (C3C4), but were not significantly affected by mutations of the PKC
      phosphorylation site (S41) or deletion of the C terminus (177-226).
      Cotransfection of B-50 with dominant negative Cdc42 or Rac did not prevent B-50
      induced formation of filopodial cells, whereas this process could be completely
      blocked by cotransfection with dominant negative Rho or Clostridium botulinum C3
      transferase. Conversely, constitutively active Rho induced a similar filopodial
      phenotype as B-50. We therefore propose that the induction of surface extensions
      by B-50 in spreading Rat-1 fibroblasts depends on Rho-guanosine triphosphatase
      function.

PMID- 9614175
TI  - The UNI3 gene is required for assembly of basal bodies of Chlamydomonas and
      encodes delta-tubulin, a new member of the tubulin superfamily.
AB  - We have cloned the UNI3 gene in Chlamydomonas and find that it encodes a new
      member of the tubulin superfamily. Although Uni3p shares significant sequence
      identity with alpha-, beta-, and gamma-tubulins, there is a region of Uni3p that
      has no similarity to tubulins or other known proteins. Mutant uni3-1 cells
      assemble zero, one, or two flagella. Pedigree analysis suggests that flagellar
      number in uni3-1 cells is a function of the age of the cell. The uniflagellate
      uni3-1 cells show a positional phenotype; the basal body opposite the eyespot
      templates the single flagellum. A percentage of uni3-1 cells also fail to orient
      the cleavage furrow properly, and basal bodies have been implicated in the
      placement of cleavage furrows in Chlamydomonas. Finally when uni3-1 cells are
      observed by electron microscopy, doublet rather than triplet microtubules are
      observed at the proximal end of the basal bodies. We propose that the Uni3
      tubulin is involved in both the function and cell cycle-dependent maturation of
      basal bodies/centrioles.

PMID- 9614176
TI  - Cyclin B proteolysis and the cyclin-dependent kinase inhibitor rum1p are required
      for pheromone-induced G1 arrest in fission yeast.
AB  - The blocking of G1 progression by fission yeast pheromones requires inhibition of
      the cyclin-dependent kinase cdc2p associated with the B-cyclins cdc13p and cig2p.
      We show that cyclosome-mediated degradation of cdc13p and cig2p is necessary for
      down-regulation of B-cyclin-associated cdc2p kinase activity and for phermone
      induced G1 arrest. The cyclin-dependent kinase inhibitor rum1p is also required
      to maintain this G1 arrest; it binds both cdc13p and cig2p and is specifically
      required for cdc13p proteolysis. We propose that rum1p acts as an adaptor
      targeting cdc13p for degradation by the cyclosome. In contrast, the cig2p-cdc2p
      kinase can be down-regulated, and the cyclin cig2p can be proteolyzed
      independently of rum1p. We suggest that pheromone signaling inhibits the cig2p
      cdc2p kinase, bringing about a transient G1 arrest. As a consequence, rum1p
      levels increase, thus inhibiting and inducing proteolysis of the cdc13p-cdc2p
      kinase; this is necessary to maintain G1 arrest. We have also shown that
      pheromone-induced transcription occurs only in G1 and is independent of rum1p.

PMID- 9614177
TI  - ADP-ribosylation factor 1 transiently activates high-affinity adaptor protein
      complex AP-1 binding sites on Golgi membranes.
AB  - Association of the Golgi-specific adaptor protein complex 1 (AP-1) with the
      membrane is a prerequisite for clathrin coat assembly on the trans-Golgi network
      (TGN). The AP-1 adaptor is efficiently recruited from cytosol onto the TGN by
      myristoylated ADP-ribosylation factor 1 (ARF1) in the presence of the poorly
      hydrolyzable GTP analog guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS).
      Substituting GTP for GTPgammaS, however, results in only poor AP-1 binding. Here
      we show that both AP-1 and clathrin can be recruited efficiently onto the TGN in
      the presence of GTP when cytosol is supplemented with ARF1. Optimal recruitment
      occurs at 4 microM ARF1 and with 1 mM GTP. The AP-1 recruited by ARF1.GTP is
      released from the Golgi membrane by treatment with 1 M Tris-HCl (pH 7) or upon
      reincubation at 37 degreesC, whereas AP-1 recruited with GTPgammaS or by a
      constitutively active point mutant, ARF1(Q71L), remains membrane bound after
      either treatment. An incubation performed with added ARF1, GTP, and AlFn, used to
      block ARF GTPase-activating protein activity, results in membrane-associated AP
      1, which is largely insensitive to Tris extraction. Thus, ARF1. GTP hydrolysis
      results in lower-affinity binding of AP-1 to the TGN. Using two-stage assays in
      which ARF1.GTP first primes the Golgi membrane at 37 degreesC, followed by AP-1
      binding on ice, we find that the high-affinity nucleating sites generated in the
      priming stage are rapidly lost. In addition, the AP-1 bound to primed Golgi
      membranes during a second-stage incubation on ice is fully sensitive to Tris
      extraction, indicating that the priming stage has passed the ARF1.GTP hydrolysis
      point. Thus, hydrolysis of ARF1.GTP at the priming sites can occur even before AP
      1 binding. Our finding that purified clathrin-coated vesicles contain little ARF1
      supports the concept that ARF1 functions in the coat assembly process rather than
      during the vesicle-uncoating step. We conclude that ARF1 is a limiting factor in
      the GTP-stimulated recruitment of AP-1 in vitro and that it appears to function
      in a stoichiometric manner to generate high-affinity AP-1 binding sites that have
      a relatively short half-life.

PMID- 9614178
TI  - Heat stress activates fission yeast Spc1/StyI MAPK by a MEKK-independent
      mechanism.
AB  - Fission yeast Spc1/StyI MAPK is activated by many environmental insults including
      high osmolarity, oxidative stress, and heat shock. Spc1/StyI is activated by
      Wis1, a MAPK kinase (MEK), which is itself activated by Wik1/Wak1/Wis4, a MEK
      kinase (MEKK). Spc1/StyI is inactivated by the tyrosine phosphatases Pyp1 and
      Pyp2. Inhibition of Pyp1 was recently reported to play a crucial role in the
      oxidative stress and heat shock responses. These conclusions were based on three
      findings: 1) osmotic, oxidative, and heat stresses activate Spc1/StyI in wis4
      cells; 2) oxidative stress and heat shock activate Spc1/StyI in cells that
      express Wis1AA, in which MEKK consensus phosphorylation sites were replaced with
      alanine; and 3) Spc1/StyI is maximally activated in Deltapyp1 cells. Contrary to
      these findings, we report: 1) Spc1/StyI activation by osmotic stress is greatly
      reduced in wis4 cells; 2) wis1-AA and Deltawis1 cells have identical phenotypes;
      and 3) all forms of stress activate Spc1/StyI in Deltapyp1 cells. We also report
      that heat shock, but not osmotic or oxidative stress, activate Spc1 in wis1-DD
      cells, which express Wis1 protein that has the MEKK consensus phosphorylation
      sites replaced with aspartic acid. Thus osmotic and oxidative stress activate
      Spc1/StyI by a MEKK-dependent process, whereas heat shock activates Spc1/StyI by
      a novel mechanism that does not require MEKK activation or Pyp1 inhibition.

PMID- 9614179
TI  - A role for the lumenal domain in Golgi localization of the Saccharomyces
      cerevisiae guanosine diphosphatase.
AB  - Integral membrane proteins (IMPs) contain localization signals necessary for
      targeting to their resident subcellular compartments. To define signals that
      mediate localization to the Golgi complex, we have analyzed a resident IMP of the
      Saccharomyces cerevisiae Golgi complex, guanosine diphosphatase (GDPase). GDPase,
      which is necessary for Golgi-specific glycosylation reactions, is a type II IMP
      with a short amino-terminal cytoplasmic domain, a single transmembrane domain
      (TMD), and a large catalytic lumenal domain. Regions specifying Golgi
      localization were identified by analyzing recombinant proteins either lacking
      GDPase domains or containing corresponding domains from type II vacuolar IMPs.
      Neither deletion nor substitution of the GDPase cytoplasmic domain perturbed
      Golgi localization. Exchanging the GDPase TMD with vacuolar protein TMDs only
      marginally affected Golgi localization. Replacement of the lumenal domain
      resulted in mislocalization of the chimeric protein from the Golgi to the
      vacuole, but a similar substitution leaving 34 amino acids of the GDPase lumenal
      domain intact was properly localized. These results identify a major Golgi
      localization determinant in the membrane-adjacent lumenal region (stem) of
      GDPase. Although necessary, the stem domain is not sufficient to mediate
      localization; in addition, a membrane-anchoring domain and either the cytoplasmic
      or full-length lumenal domain must be present to maintain Golgi residence. The
      importance of lumenal domain sequences in GDPase Golgi localization and the
      requirement for multiple hydrophilic protein domains support a model for Golgi
      localization invoking protein-protein interactions rather than interactions
      between the TMD and the lipid bilayer.

PMID- 9614180
TI  - Inhibition of Rho is required for cAMP-induced melanoma cell differentiation.
AB  - Up-regulation of the cAMP pathway by forskolin or alpha-melanocyte stimulating
      hormone induces melanocyte and melanoma cell differentiation characterized by
      stimulation of melanin synthesis and dendrite development. Here we show that
      forskolin-induced dendricity is associated to a disassembly of actin stress
      fibers. Since Rho controls actin organization, we studied the role of this
      guanosine triphosphate (GTP)-binding protein in cAMP-induced dendrite formation.
      Clostridium botulinum C3 exotransferase, which inhibits Rho, mimicked the effect
      of forskolin in promoting dendricity and stress fiber disruption, while the
      Escherichia coli toxin cytotoxic necrotizing factor-1 (CNF-1), which activates
      Rho and the expression of a constitutively active Rho mutant, blocked forskolin
      induced dendrite outgrowth. In addition, overexpression of a constitutively
      active form of the Rho target p160 Rho-kinase (P160(ROCK)) prevented the
      dendritogenic effects of cAMP. Our results suggest that inhibition of Rho and of
      its target p160(ROCK) are required events for cAMP-induced dendrite outgrowth in
      B16 cells. Furthermore, we present evidence that Rho is involved in the
      regulation of melanogenesis. Indeed, Rho inactivation enhanced the cAMP
      stimulation of tyrosinase gene transcription and protein expression, while Rho
      constitutive activation impaired these cAMP-induced effects. This reveals that,
      in addition to controlling dendricity, Rho also participates in the regulation of
      melanin synthesis by cAMP.

PMID- 9614181
TI  - RhoG GTPase controls a pathway that independently activates Rac1 and Cdc42Hs.
AB  - RhoG is a member of the Rho family of GTPases that shares 72% and 62% sequence
      identity with Rac1 and Cdc42Hs, respectively. We have expressed mutant RhoG
      proteins fused to the green fluorescent protein and analyzed subsequent changes
      in cell surface morphology and modifications of cytoskeletal structures. In rat
      and mouse fibroblasts, green fluorescent protein chimera and endogenous RhoG
      proteins colocalize according to a tubular cytoplasmic pattern, with perinuclear
      accumulation and local concentration at the plasma membrane. Constitutively
      active RhoG proteins produce morphological and cytoskeletal changes similar to
      those elicited by a simultaneous activation of Rac1 and Cdc42Hs, i.e., the
      formation of ruffles, lamellipodia, filopodia, and partial loss of stress fibers.
      In addition, RhoG and Cdc42Hs promote the formation of microvilli at the cell
      apical membrane. RhoG-dependent events are not mediated through a direct
      interaction with Rac1 and Cdc42Hs targets such as PAK-1, POR1, or WASP proteins
      but require endogenous Rac1 and Cdc42Hs activities: coexpression of a dominant
      negative Rac1 impairs membrane ruffling and lamellipodia but not filopodia or
      microvilli formation. Conversely, coexpression of a dominant negative Cdc42Hs
      only blocks microvilli and filopodia, but not membrane ruffling and lamellipodia.
      Microtubule depolymerization upon nocodazole treatment leads to a loss of RhoG
      protein from the cell periphery associated with a reversal of the RhoG phenotype,
      whereas PDGF or bradykinin stimulation of nocodazole-treated cells could still
      promote Rac1- and Cdc42Hs-dependent cytoskeletal reorganization. Therefore, our
      data demonstrate that RhoG controls a pathway that requires the microtubule
      network and activates Rac1 and Cdc42Hs independently of their growth factor
      signaling pathways.

PMID- 9614182
TI  - Distinct morphological phenotypes of cell fusion mutants.
AB  - Cell fusion in yeast is the process by which two haploid cells fuse to form a
      diploid zygote. To dissect the pathway of cell fusion, we phenotypically and
      genetically characterized four cell fusion mutants, fus6/spa2, fus7/rvs161, fus1,
      and fus2. First, we examined the complete array of single and double mutants. In
      all cases but one, double mutants exhibited stronger cell fusion defects than
      single mutants. The exception was rvs161Delta fus2Delta, suggesting that Rvs161p
      and Fus2p act in concert. Dosage suppression analysis showed that Fus1p and Fus2p
      act downstream or parallel to Rvs161p and Spa2p. Second, electron microscopic
      analysis was used to define the mutant defects in cell fusion. In wild-type
      prezygotes vesicles were aligned and clustered across the cell fusion zone. The
      vesicles were associated with regions of cell wall thinning. Analysis of Fus-
      zygotes indicated that Fus1p was required for the normal localization of the
      vesicles to the zone of cell fusion, and Spa2p facilitated their clustering. In
      contrast, Fus2p and Rvs161p appeared to act after vesicle positioning. These
      findings lead us to propose that cell fusion is mediated in part by the localized
      release of vesicles containing components essential for cell fusion.

PMID- 9614183
TI  - Collagenase-3 induction in rat lung fibroblasts requires the combined effects of
      tumor necrosis factor-alpha and 12-lipoxygenase metabolites: a model of
      macrophage-induced, fibroblast-driven extracellular matrix remodeling during
      inflammatory lung injury.
AB  - The mechanisms responsible for the induction of matrix-degrading proteases during
      lung injury are ill defined. Macrophage-derived mediators are believed to play a
      role in regulating synthesis and turnover of extracellular matrix at sites of
      inflammation. We find a localized increase in the expression of the rat
      interstitial collagenase (MMP-13; collagenase-3) gene from fibroblastic cells
      directly adjacent to macrophages within silicotic rat lung granulomas.
      Conditioned medium from macrophages isolated from silicotic rat lungs was found
      to induce rat lung fibroblast interstitial collagenase gene expression.
      Conditioned medium from primary rat lung macrophages or J774 monocytic cells
      activated by particulates in vitro also induced interstitial collagenase gene
      expression. Tumor necrosis factor-alpha (TNF-alpha) alone did not induce
      interstitial collagenase expression in rat lung fibroblasts but did in rat skin
      fibroblasts, revealing tissue specificity in the regulation of this gene. The
      activity of the conditioned medium was found to be dependent on the combined
      effects of TNF-alpha and 12-lipoxygenase-derived arachidonic acid metabolites.
      The fibroblast response to this conditioned medium was dependent on de novo
      protein synthesis and involved the induction of nuclear activator protein-1
      activity. These data reveal a novel requirement for macrophage-derived 12
      lipoxygenase metabolites in lung fibroblast MMP induction and provide a mechanism
      for the induction of resident cell MMP gene expression during inflammatory lung
      processes.

PMID- 9614184
TI  - Identification of osteopontin as a novel ligand for the integrin alpha8 beta1 and
      potential roles for this integrin-ligand interaction in kidney morphogenesis.
AB  - Epithelio-mesenchymal interactions during kidney organogenesis are disrupted in
      integrin alpha8 beta1-deficient mice. However, the known ligands for integrin
      alpha8 beta1-fibronectin, vitronectin, and tenascin-C-are not appropriately
      localized to mediate all alpha8 beta1 functions in the kidney. Using a method of
      general utility for determining the distribution of unknown integrin ligands in
      situ and biochemical characterization of these ligands, we identified osteopontin
      (OPN) as a ligand for alpha8 beta1. We have coexpressed the extracellular domains
      of the mouse alpha8 and beta1 integrin subunits as a soluble heterodimer with one
      subunit fused to alkaline phosphatase (AP) and have used the alpha8 beta1-AP
      chimera as a histochemical reagent on sections of mouse embryos. Ligand
      localization with alpha8 beta1-AP in developing bone and kidney was observed to
      be overlapping with the distribution of OPN. In "far Western" blots of mouse
      embryonic protein extracts, bands were detected with sizes corresponding to
      fibronectin, vitronectin, and unknown proteins, one of which was identical to the
      size of OPN. In a solid-phase binding assay we demonstrated that purified OPN
      binds specifically to alpha8 beta1-AP. Cell adhesion assays using K562 cells
      expressing alpha8 beta1 were used to confirm this result. Together with a recent
      report that anti-OPN antibodies disrupt kidney morphogenesis, our results suggest
      that interactions between OPN and integrin alpha8 beta1 may help regulate kidney
      development and other morphogenetic processes.

PMID- 9614185
TI  - A novel tetanus neurotoxin-insensitive vesicle-associated membrane protein in
      SNARE complexes of the apical plasma membrane of epithelial cells.
AB  - The importance of soluble N-ethyl maleimide (NEM)-sensitive fusion protein (NSF)
      attachment protein (SNAP) receptors (SNAREs) in synaptic vesicle exocytosis is
      well established because it has been demonstrated that clostridial neurotoxins
      (NTs) proteolyze the vesicle SNAREs (v-SNAREs) vesicle-associated membrane
      protein (VAMP)/brevins and their partners, the target SNAREs (t-SNAREs) syntaxin
      1 and SNAP25. Yet, several exocytotic events, including apical exocytosis in
      epithelial cells, are insensitive to numerous clostridial NTs, suggesting the
      presence of SNARE-independent mechanisms of exocytosis. In this study we found
      that syntaxin 3, SNAP23, and a newly identified VAMP/brevin, tetanus neurotoxin
      (TeNT)-insensitive VAMP (TI-VAMP), are insensitive to clostridial NTs. In
      epithelial cells, TI-VAMP-containing vesicles were concentrated in the apical
      domain, and the protein was detected at the apical plasma membrane by immunogold
      labeling on ultrathin cryosections. Syntaxin 3 and SNAP23 were codistributed at
      the apical plasma membrane where they formed NEM-dependent SNARE complexes with
      TI-VAMP and cellubrevin. We suggest that TI-VAMP, SNAP23, and syntaxin 3 can
      participate in exocytotic processes at the apical plasma membrane of epithelial
      cells and, more generally, domain-specific exocytosis in clostridial NT-resistant
      pathways.

PMID- 9614186
TI  - The activity of differentiation factors induces apoptosis in polyomavirus large T
      expressing myoblasts.
AB  - It is commonly accepted that pathways that regulate proliferation/differentiation
      processes, if altered in their normal interplay, can lead to the induction of
      programmed cell death. In a previous work we reported that Polyoma virus Large
      Tumor antigen (PyLT) interferes with in vitro terminal differentiation of
      skeletal myoblasts by binding and inactivating the retinoblastoma antioncogene
      product. This inhibition occurs after the activation of some early steps of the
      myogenic program. In the present work we report that myoblasts expressing wild
      type PyLT, when subjected to differentiation stimuli, undergo cell death and that
      this cell death can be defined as apoptosis. Apoptosis in PyLT-expressing
      myoblasts starts after growth factors removal, is promoted by cell confluence,
      and is temporally correlated with the expression of early markers of myogenic
      differentiation. The block of the initial events of myogenesis by transforming
      growth factor beta or basic fibroblast growth factor prevents PyLT-induced
      apoptosis, while the acceleration of this process by the overexpression of the
      muscle-regulatory factor MyoD further increases cell death in this system. MyoD
      can induce PyLT-expressing myoblasts to accumulate RB, p21, and muscle- specific
      genes but is unable to induce G0(0) arrest. Several markers of different phases
      of the cell cycle, such as cyclin A, cdk-2, and cdc-2, fail to be down-regulated,
      indicating the occurrence of cell cycle progression. It has been frequently
      suggested that apoptosis can result from an unbalanced cell cycle progression in
      the presence of a contrasting signal, such as growth factor deprivation. Our data
      involve differentiation pathways, as a further contrasting signal, in the
      generation of this conflict during myoblast cell apoptosis.

PMID- 9614188
TI  - Effects of age on the posttranscriptional regulation of CCAAT/enhancer binding
      protein alpha and CCAAT/enhancer binding protein beta isoform synthesis in
      control and LPS-treated livers.
AB  - The CCAAT/enhancer binding protein alpha (C/EBPalpha) and CCAAT/enhancer binding
      protein beta (C/EBPbeta) mRNAs are templates for the differential translation of
      several isoforms. Immunoblotting detects C/EBPalphas with molecular masses of 42,
      38, 30, and 20 kDa and C/EBPbetas of 35, 20, and approximately 8.5 kDa. The DNA
      binding activities and pool levels of p42(C/EBPalpha) and p30(C/EBPalpha) in
      control nuclear extracts decrease significantly whereas the binding activity and
      protein levels of the 20-kDa isoforms increase dramatically with LPS treatment.
      Our studies suggest that the LPS response involves alternative translational
      initiation at specific in-frame AUGs, producing specific C/EBPalpha and C/EBPbeta
      isoform patterns. We propose that alternative translational initiation occurs by
      a leaky ribosomal scanning mechanism. We find that nuclear extracts from normal
      aged mouse livers have decreased p42(C/EBPalpha) levels and binding activity,
      whereas those of p20(C/EBPalpha) and p20(C/EBPbeta) are increased. However,
      translation of 42-kDa C/EBPalpha is not down-regulated on polysomes, suggesting
      that aging may affect its nuclear translocation. Furthermore, recovery of the
      C/EBPalpha- and C/EBPbeta-binding activities and pool levels from an LPS
      challenge is delayed significantly in aged mouse livers. Thus, aged livers have
      altered steady-state levels of C/EBPalpha and C/EBPbeta isoforms. This result
      suggests that normal aging liver exhibits characteristics of chronic stress and a
      severe inability to recover from an inflammatory challenge.

PMID- 9614187
TI  - Calcium-dependent clustering of inositol 1,4,5-trisphosphate receptors.
AB  - Rat basophilic leukemia (RBL-2H3) cells predominantly express the type II
      receptor for inositol 1,4,5-trisphosphate (InsP3), which operates as an InsP3
      gated calcium channel. In these cells, cross-linking the high-affinity
      immunoglobulin E receptor (FcepsilonR1) leads to activation of phospholipase C
      gamma isoforms via tyrosine kinase- and phosphatidylinositol 3-kinase-dependent
      pathways, release of InsP3-sensitive intracellular Ca2+ stores, and a sustained
      phase of Ca2+ influx. These events are accompanied by a redistribution of type II
      InsP3 receptors within the endoplasmic reticulum and nuclear envelope, from a
      diffuse pattern with a few small aggregates in resting cells to large isolated
      clusters after antigen stimulation. Redistribution of type II InsP3 receptors is
      also seen after treatment of RBL-2H3 cells with ionomycin or thapsigargin. InsP3
      receptor clustering occurs within 5-10 min of stimulus and persists for up to 1 h
      in the presence of antigen. Receptor clustering is independent of endoplasmic
      reticulum vesiculation, which occurs only at ionomycin concentrations >1 microM,
      and maximal clustering responses are dependent on the presence of extracellular
      calcium. InsP3 receptor aggregation may be a characteristic cellular response to
      Ca2+-mobilizing ligands, because similar results are seen after activation of
      phospholipase C-linked G-protein-coupled receptors; cholecystokinin causes type
      II receptor redistribution in rat pancreatoma AR4-2J cells, and carbachol causes
      type III receptor redistribution in muscarinic receptor-expressing hamster lung
      fibroblast E36(M3R) cells. Stimulation of these three cell types leads to a
      reduction in InsP3 receptor levels only in AR4-2J cells, indicating that receptor
      clustering does not correlate with receptor down-regulation. The calcium
      dependent aggregation of InsP3 receptors may contribute to the previously
      observed changes in affinity for InsP3 in the presence of elevated Ca2+ and/or
      may establish discrete regions within refilled stores with varying capacity to
      release Ca2+ when a subsequent stimulus results in production of InsP3.

PMID- 9614189
TI  - The endogenous and cell cycle-dependent phosphorylation of tau protein in living
      cells: implications for Alzheimer's disease.
AB  - In Alzheimer's disease the neuronal microtubule-associated protein tau becomes
      highly phosphorylated, loses its binding properties, and aggregates into paired
      helical filaments. There is increasing evidence that the events leading to this
      hyperphosphorylation are related to mitotic mechanisms. Hence, we have analyzed
      the physiological phosphorylation of endogenous tau protein in metabolically
      labeled human neuroblastoma cells and in Chinese hamster ovary cells stably
      transfected with tau. In nonsynchronized cultures the phosphorylation pattern was
      remarkably similar in both cell lines, suggesting a similar balance of kinases
      and phosphatases with respect to tau. Using phosphopeptide mapping and sequencing
      we identified 17 phosphorylation sites comprising 80-90% of the total phosphate
      incorporated. Most of these are in SP or TP motifs, except S214 and S262. Since
      phosphorylation of microtubule-associated proteins increases during mitosis,
      concomitant with increased microtubule dynamics, we analyzed cells mitotically
      arrested with nocodazole. This revealed that S214 is a prominent phosphorylation
      site in metaphase, but not in interphase. Phosphorylation of this residue
      strongly decreases the tau-microtubule interaction in vitro, suppresses
      microtubule assembly, and may be a key factor in the observed detachment of tau
      from microtubules during mitosis. Since S214 is also phosphorylated in
      Alzheimer's disease tau, our results support the view that reactivation of the
      cell cycle machinery is involved in tau hyperphosphorylation.

PMID- 9614191
TI  - Numbers and organization of RNA polymerases, nascent transcripts, and
      transcription units in HeLa nuclei.
AB  - Using HeLa cells, we have developed methods to determine 1) the number of RNA
      polymerases that are active at any moment, 2) the number of transcription sites,
      and 3) the number of polymerases associated with one transcription unit. To count
      engaged polymerases, cells were encapsulated in agarose, permeabilized, treated
      with ribonuclease, and the now-truncated transcripts extended in [32P]uridine
      triphosphate; then, the number of growing transcripts was calculated from the
      total number of nucleotides incorporated and the average increment in length of
      the transcripts. Approximately 15, 000 transcripts were elongated by polymerase
      I, and approximately 75,000 were elongated by polymerases II and III.
      Transcription sites were detected after the cells were grown in bromouridine for
      <2.5 min, after which the resulting bromo-RNA was labeled with gold particles;
      electron microscopy showed that most extranucleolar transcripts were concentrated
      in approximately 2400 sites with diameters of approximately 80 nm. The number of
      polymerases associated with a transcription unit was counted after templates were
      spread over a large area; most extranucleolar units were associated with one
      elongating complex. These results suggest that many templates are attached in a
      "cloud" of loops around a site; each site, or transcription "factory," would
      contain approximately 30 active polymerases and associated transcripts.

PMID- 9614190
TI  - Delayed activation of the store-operated calcium current induced by calreticulin
      overexpression in RBL-1 cells.
AB  - Calreticulin (CRT) is a high-capacity, low-affinity Ca2+-binding protein located
      in the lumen of the endoplasmic reticulum (ER) of all eukaryotic cells
      investigated so far. Its high level of conservation among different species
      suggests that it serves functions fundamental to cell survival. The role
      originally proposed for CRT, i.e., the main Ca2+ buffer of the ER, has been
      obscured or even casted by its implication in processes as diverse as gene
      expression, protein folding, and cell adhesion. In this work we seek the role of
      CRT in Ca2+ storing and signaling by evaluating its effects on the kinetics and
      amplitude of the store-operated Ca2+ current (ICRAC). We show that, in the rat
      basophilic leukemia cell line RBL-1, overexpression of CRT, but not of its mutant
      lacking the high-capacity Ca2+-binding domain, markedly retards the ICRAC
      development, however, only when store depletion is slower than the rate of
      current activation. On the contrary, when store depletion is rapid and complete,
      overexpression of CRT has no effect. The present results are compatible with a
      major Ca2+-buffering role of CRT within the ER but exclude a direct, or indirect,
      role of this protein on the mechanism of ICRAC activation.

PMID- 9614192
TI  - Virulence and functions of myosin II are inhibited by overexpression of light
      meromyosin in Entamoeba histolytica.
AB  - Several changes in cell morphology take place during the capping of surface
      receptors in Entamoeba histolytica. The amoebae develop the uroid, an appendage
      formed by membrane invaginations, which accumulates ligand-receptor complexes
      resulting from the capping process. Membrane shedding is particularly active in
      the uroid region and leads to the elimination of accumulated ligands. This
      appendage has been postulated to participate in parasitic defense mechanisms
      against the host immune response, because it eliminates complement and specific
      antibodies bound to the amoeba surface. The involvement of myosin II in the
      capping process of surface receptors has been suggested by experiments showing
      that drugs that affect myosin II heavy-chain phosphorylation prevent this
      activity. To understand the role of this mechanoenzyme in surface receptor
      capping, a myosin II dominant negative strain was constructed. This mutant is the
      first genetically engineered cytoskeleton-deficient strain of E. histolytica. It
      was obtained by overexpressing the light meromyosin domain, which is essential
      for myosin II filament formation. E. histolytica overexpressing light meromyosin
      domain displayed a myosin II null phenotype characterized by abnormal movement,
      failure to form the uroid, and failure to undergo the capping process after
      treatment with concanavalin A. In addition, the amoebic cytotoxic capacities of
      the transfectants on human colon cells was dramatically reduced, indicating a
      role for cytoskeleton in parasite pathogenicity.

PMID- 9614193
TI  - Endobrevin, a novel synaptobrevin/VAMP-like protein preferentially associated
      with the early endosome.
AB  - Synaptobrevins/vesicle-associated membrane proteins (VAMPs) together with
      syntaxins and a synaptosome-associated protein of 25 kDa (SNAP-25) are the main
      components of a protein complex involved in the docking and/or fusion of synaptic
      vesicles with the presynaptic membrane. We report here the molecular,
      biochemical, and cell biological characterization of a novel member of the
      synaptobrevin/VAMP family. The amino acid sequence of endobrevin has 32, 33, and
      31% identity to those of synaptobrevin/VAMP-1, synaptobrevin/VAMP-2, and
      cellubrevin, respectively. Membrane fractionation studies demonstrate that
      endobrevin is enriched in membrane fractions that are also enriched in the
      asialoglycoprotein receptor. Indirect immunofluorescence microscopy establishes
      that endobrevin is primarily associated with the perinuclear vesicular structures
      of the early endocytic compartment. The preferential association of endobrevin
      with the early endosome was further established by electron microscopy (EM)
      immunogold labeling. In vitro binding assays show that endobrevin interacts with
      immobilized recombinant alpha-SNAP fused to glutathione S-transferase (GST). Our
      results highlight the general importance of members of the synaptobrevin/VAMP
      protein family in membrane traffic and provide new avenues for future functional
      and mechanistic studies of this protein as well as the endocytotic pathway.

PMID- 9614194
TI  - Chs6p-dependent anterograde transport of Chs3p from the chitosome to the plasma
      membrane in Saccharomyces cerevisiae.
AB  - Chitin synthase III (CSIII), an enzyme required to form a chitin ring in the
      nascent division septum of Saccharomyces cerevisiae, may be transported to the
      cell surface in a regulated manner. Chs3p, the catalytic subunit of CSIII,
      requires the product of CHS6 to be transported to or activated at the cell
      surface. We find that chs6Delta strains have morphological abnormalities similar
      to those of chs3 mutants. Subcellular fractionation and indirect
      immunofluorescence indicate that Chs3p distribution is altered in chs6 mutant
      cells. Order-of-function experiments using end4-1 (endocytosis-defective) and
      chs6 mutants indicate that Chs6p is required for anterograde transport of Chs3p
      from an internal endosome-like membrane compartment, the chitosome, to the plasma
      membrane. As a result, chs6 strains accumulate Chs3p in chitosomes. Chs1p, a
      distinct chitin synthase that acts during or after cell separation, is
      transported normally in chs6 mutants, suggesting that Chs1p and Chs3p are
      independently packaged during protein transport through the late secretory
      pathway.

PMID- 9614195
TI  - Functional domains of rep2, a transcriptional activator subunit for Res2-Cdc10,
      controlling the cell cycle "start".
AB  - In the fission yeast Schizosaccharomyces pombe, passage from G1 to S-phase
      requires the execution of the transcriptional factor complex that consists of the
      Cdc10 and Res1/2 molecules. This complex activates the MluI cell cycle box cis
      element contained in genes essential for S-phase onset and progression. The
      rep2(+) gene, isolated as a multicopy suppressor of a temperature-sensitive cdc10
      mutant, has been postulated to encode a putative transcriptional activator
      subunit for the Res2-Cdc10 complex. To identify the rep2(+) function and
      molecularly define its domain organization, we reconstituted the Res2-Cdc10
      complex-dependent transcriptional activation in Saccharomyces cerevisiae.
      Reconstitution experiments, deletion analyses using one and two hybrid systems,
      and in vivo Res2 coimmunoprecipitation assays show that the Res2-Cdc10 complex
      itself can recognize but cannot activate MluI cell cycle box without Rep2, and
      that consistent with its postulated function, Rep2 contains 45-amino acid Res2
      binding and 22-amino acid transcriptional activation domains in the middle and C
      terminus of the molecule, respectively. The functional essentiality of these
      domains is also demonstrated by their requirement for rescue of the cold
      sensitive rep2 deletion mutant of fission yeast.

PMID- 9614197
TI  - Trinitrophenyl-substituted nucleotides are potent antagonists selective for P2X1,
      P2X3, and heteromeric P2X2/3 receptors.
AB  - There are currently seven P2X receptor subunits (P2X1-7) defined by molecular
      cloning. The functional identification of these receptors has relied primarily on
      the potency of alpha,beta-methylene-ATP relative to that of ATP and on the
      kinetics of receptor desensitization. In the present experiments we found that
      the 2', 3'-O-(2,4,6-trinitrophenyl)-substituted analogs of ATP are selective and
      potent antagonists at some but not all P2X receptors. The trinitrophenyl analogs
      of ATP, ADP, AMP, and GTP produced a reversible inhibition of ATP-evoked currents
      in human embryonic kidney 293 cells expressing P2X1 receptors, P2X3 receptors, or
      both P2X2 and P2X3 (heteromeric) receptors; IC50 values were close to 1 nM. These
      compounds were at least 1000-fold less effective in blocking currents in cells
      expressing P2X2, P2X4, or P2X7 receptors (P2X5 and P2X6 not tested). GTP, 2,4,6
      trinitrophenol, and the 2',3'-trinitrophenyl analog of adenosine (0.1-10 microM)
      had no effect. Thus, we have identified a structural motif that confers
      antagonist action at P2X receptors that contain P2X1 or P2X3 subunits (the
      alpha,beta-methylene-ATP-sensitive subclass).

PMID- 9614196
TI  - Cleavage of beta-catenin and plakoglobin and shedding of VE-cadherin during
      endothelial apoptosis: evidence for a role for caspases and metalloproteinases.
AB  - Growth factor deprivation of endothelial cells induces apoptosis, which is
      characterized by membrane blebbing, cell rounding, and subsequent loss of cell
      matrix and cell-cell contacts. In this study, we show that initiation of
      endothelial apoptosis correlates with cleavage and disassembly of intracellular
      and extracellular components of adherens junctions. beta-Catenin and plakoglobin,
      which form intracellular links between vascular endothelial cadherin (VE
      cadherin) and actin-binding alpha-catenin in adherens junctions, are cleaved in
      apoptotic cells. In vitro incubations of cell lysates and immunoprecipitates with
      recombinant caspases indicate that CPP32 and Mch2 are involved, possibly by
      initiating proteolytic processing. Cleaved beta-catenin from lysates of apoptotic
      cells does not bind to endogenous alpha-catenin, whereas plakoglobin retains its
      binding capacity. The extracellular portion of the adherens junctions is also
      altered during apoptosis because VE-cadherin, which mediates endothelial cell
      cell interactions, dramatically decreases on the surface of cells. An
      extracellular fragment of VE-cadherin can be detected in the conditioned medium,
      and this "shedding" of VE-cadherin can be blocked by an inhibitor of
      metalloproteinases. Thus, cleavage of beta-catenin and plakoglobin and shedding
      of VE-cadherin may act in concert to disrupt structural and signaling properties
      of adherens junctions and may actively interrupt extracellular signals required
      for endothelial cell survival.

PMID- 9614198
TI  - Privileged access to mitochondria of calcium influx through N-methyl-D-aspartate
      receptors.
AB  - Mitochondrial Ca2+ uptake responds dynamically and sensitively to changes in
      cytosolic Ca2+ levels and plays a crucial role in sequestering the large Ca2+
      load induced by N-methyl-D-aspartate (NMDA) receptor activation. However, the
      precise interrelationships between NMDA receptor activation, cytosolic Ca2+
      increase, and mitochondrial Ca2+ uptake remain obscure. To reliably,
      independently, and simultaneously detect cytosolic and mitochondrial Ca2+
      concentration changes in the same cell, we loaded primary striatal neurons with
      two Ca2+ indicators, calcium green 1N and rhod-2, and visualized the fluorescence
      signals from single neurons with laser scanning confocal fluorescence microscopy.
      In kinetic data analysis, only calcium green signals from predefined cytosolic
      areas and rhod-2 signals from predefined mitochondrial regions were used, and
      attention was focused on the initial rapid rising phase of the responses. When
      neurons were treated with 100 microM NMDA, increases of cytosolic and
      mitochondrial Ca2+ showed similar time courses and rates of change, and seemed to
      be time-locked. In contrast, when neurons were treated with 100 microM kainate,
      50 mM KCl, or 0.3 microM ionomycin, mitochondrial Ca2+ increases lagged behind
      cytosolic Ca2+ increases. These data suggest that mitochondrial Ca2+ uptake in
      response to an increase of cytosolic Ca2+ is faster and more tightly coupled
      during NMDA receptor activation than during non-NMDA receptor or voltage
      dependent Ca2+ channel activation. This proficient mitochondrial Ca2+ uptake may
      avert a large rise in cytosolic Ca2+ concentration in response to NMDA receptor
      activation. Yet, it may lead to excessive Ca2+ accumulation inside mitochondria
      and render mitochondria susceptible to Ca2+ mediated injury.

PMID- 9614200
TI  - A comparison of the oxidation of clozapine and olanzapine to reactive metabolites
      and the toxicity of these metabolites to human leukocytes.
AB  - Olanzapine was shown to be oxidized to a reactive intermediate by HOCl, which is
      the major oxidant produced by activated neutrophils. A mass spectrum obtained
      using a flow system in which the reactants were fed into a mixing chamber and the
      products flowed directly into a mass spectrometer revealed a reactive
      intermediate at m/z 311. This is 2 mass units less than the protonated molecular
      ion of parent olanzapine and suggests that the reactive intermediate is a
      nitrenium ion. The reactive intermediate could be trapped with glutathione or N
      acetylcysteine to produce two conjugates. These data are analogous to results we
      reported previously with the structurally related atypical antipsychotic agent
      clozapine. However, the clozapine and olanzapine reactive metabolites showed
      differences in their ability to cause toxicity to human neutrophils. Toxicity to
      neutrophils was observed only at high concentrations of clozapine (>50 microM)
      when HOCl was used to generate reactive metabolite. In contrast, concentration
      dependent toxicity (p < 0.05) was observed when neutrophils were incubated with
      clozapine (0-20 microM) and H2O2 to generate clozapine reactive metabolite. No
      toxicity was observed with clozapine alone (at concentrations of > 50 microM).
      Similar results were observed in monocytes and HL-60 cells. Olanzapine reactive
      metabolite only seemed to cause slight toxicity at the highest concentrations
      tested (20 microM), even when the reactive metabolite was generated using H2O2.
      Neutrophils from two patients with a history of clozapine-induced agranulocytosis
      seemed to be more sensitive to the toxic effects of the clozapine reactive
      metabolite; however, the numbers are too small to draw any definite conclusions.

PMID- 9614199
TI  - Receptor-mediated activation of Gsalpha: evidence for intramolecular signal
      transduction.
AB  - To investigate the mechanism by which cell surface receptors activate
      heterotrimeric G proteins, we applied a scanning mutagenesis approach to the
      carboxyl-terminal 40% of alphas (residues 236-394) to identify residues that play
      a role in receptor-mediated activation. We identified four regions of sequence in
      which mutations significantly impaired receptor-dependent stimulation of cAMP
      synthesis in transiently transfected cyc- S49 lymphoma cells, which lack
      endogenous alphas. Residues at the carboxyl terminus are likely to be receptor
      contact sites. Buried residues near the bound GDP are connected to the carboxyl
      terminus by an alpha helix and may regulate GDP affinity. Residues in two
      adjacent loops of the GTPase domain at the interface with the helical domain, one
      of which includes a region, switch III, that changes conformation on GTP binding,
      are positioned to relay the receptor-initiated signal across the domain interface
      to facilitate GDP release. Consistent with this hypothesis, replacing the helical
      domain of alphas with that of alphai2 in an alphas/alphai2/alphas chimera
      corrects the defect in receptor-mediated activation caused by alphai2
      substitutions on the GTPase side of the interface. Thus, complementary
      interactions between residues across the domain interface seem to play a role in
      receptor-catalyzed activation.

PMID- 9614201
TI  - A comparison of the covalent binding of clozapine and olanzapine to human
      neutrophils in vitro and in vivo.
AB  - Covalent binding of a reactive metabolite of clozapine to neutrophils or their
      precursors is thought to play a role in the development of clozapine-induced
      agranulocytosis. Immunoblotting studies with an anti-clozapine antiserum detected
      covalent binding of clozapine to human neutrophils in vitro when HOCl was used to
      generate clozapine reactive metabolite (major clozapine adducts of 31, 49, 58,
      78, 86, 126, 160, and 204 kDa). In addition, incubating neutrophils with
      clozapine and H2O2 (major clozapine adducts of 49 and 58 kDa) or clozapine, H2O2,
      and human myeloperoxidase (major clozapine adducts of 31, 49, 58, and 126 kDa)
      also resulted in covalent binding of clozapine to the neutrophils. The covalent
      binding of clozapine to neutrophils was inhibited by extracellular glutathione
      when HOCl, but not H2O2 was used to generate reactive metabolite. We found that
      the antiserum against clozapine also recognized olanzapine, an antipsychotic drug
      that forms a similar reactive metabolite to clozapine but has not been associated
      with induction of agranulocytosis. Repeating the in vitro experiments with
      olanzapine revealed that the major olanzapine-modified polypeptides had molecular
      masses of 96, 130-170, and 218 kDa. Only relatively low levels of 31, 49, and 58
      kDa adducts were observed. Clozapine-modified polypeptides also were detected in
      neutrophils from patients being treated with clozapine. A major 58-kDa clozapine
      modified polypeptide was detected in all patients tested. In contrast, no drug
      modified polypeptides were detected in neutrophils from patients taking
      olanzapine. The differences in covalent binding exhibited by the two compounds
      and, in particular, the lack of olanzapine binding to human neutrophils in vivo
      may help to explain the difference in toxicity of these two drugs.

PMID- 9614202
TI  - Interleukin-1beta induces bradykinin B2 receptor gene expression through a
      prostanoid cyclic AMP-dependent pathway in human bronchial smooth muscle cells.
AB  - We investigated the hypothesis that inflammatory mediators such as interleukin
      1beta (IL-1beta) might be responsible for the hyperreactivity of asthmatic
      patients to bradykinin. In cultured human bronchial smooth muscle cells, IL-1beta
      elicited a rapid and transient increase in the density of bradykinin B2 receptors
      without affecting their affinity for ligands. The increase in B2 receptors was
      correlated to an enhancement of inositol phosphate formation elicited by
      bradykinin, indicating its relevance to the contractile response of smooth muscle
      cells to bradykinin. The increase in receptor density was related to an increase
      in B2 receptor mRNA level corresponding to a 5-fold enhancement of the
      transcriptional rate and to a lengthened half-life of mRNA. These effects of IL
      1beta were largely inhibited by indomethacin, suggesting the involvement of a
      prostanoid pathway in IL-1beta transduction process. An increase in prostaglandin
      E2 levels preceded the mRNA increase, confirming this involvement. Moreover, IL
      1beta and prostaglandin E2 led to cAMP formation. We propose this predominant
      transduction pathway of IL-1beta to stimulate the transcription of the bradykinin
      B2 gene in human bronchial smooth muscle cells as a major mechanism involved in
      the hyperresponsiveness of asthmatic patients to bradykinin.

PMID- 9614203
TI  - Negative regulation of the rat glutathione S-transferase A2 gene by
      glucocorticoids involves a canonical glucocorticoid consensus sequence.
AB  - Glucocorticoids (GCs) repress both basal and polyaromatic hydrocarbon-induced
      expression of the glutathione S-transferase Ya1 gene (gstA2) in isolated rat
      hepatocytes and rat liver in vivo. Transient transfection experiments with HepG2
      cells were used to identify GC-responsive elements (GREs). With cotransfected GC
      receptor, chloramphenicol acetyltransferase (CAT) constructs containing a
      palindromic GRE (pGRE) and three GRE hexanucleotide half-sites between -1.6 and 
      1.1 kb of the 5'-flanking region of gstA2 were repressed >50% by GC when induced
      with polyaromatic hydrocarbon. This pGRE, if either mutated or deleted,
      significantly reduces GC responsiveness of the gene to 20-30%; no effect of GC
      was observed with CAT constructs containing -1.15 kb of the 5'-flanking region.
      The dexamethasone concentration dependence of the repression was consistent with
      involvement of the GC receptor and was antagonized by RU38486. Electrophoretic
      mobility shift assays demonstrated that pGRE formed a specific DNA/protein
      complex, which was prevented by the addition of excess unlabeled or mouse mammary
      tumor virus GRE but not by unrelated or mutated gstA2 GRE double-stranded
      oligonucleotides. This complex was supershifted by incubation of nuclear extracts
      containing GC receptor with anti-GC receptor globulins. Constructs containing
      multiple copies of pGRE sequence were either nonresponsive or positively
      responsive (three copies) to GC. Luciferase constructs containing -1.62 to -1.03
      kb of the 5'-flanking region also were regulated positively by GC. Chimeric GC
      peroxisome proliferator activated receptor activated the constructs that were
      positively responsive to GC but did not mediate the negative effect in constructs
      containing 1.6 kb of 5'-flanking region. We conclude that pGRE and half-site GREs
      of gstA2 participate in regulation of this gene; however, a second unidentified
      responsive element must exist between -1.03 and -0.164 kb, resulting in
      repression of gstA2 expression.

PMID- 9614204
TI  - C/EBPalpha is a regulator of the UDP glucuronosyltransferase UGT2B1 gene.
AB  - The rat UDP glucuronosyltransferase, UGT2B1, is expressed in the liver where it
      glucuronidates steroids, environmental toxins, and carcinogens. A region between 
      88 and -111 base pairs upstream from the UGT2B1 gene transcription start site
      contains a CCAAT enhancer binding protein (C/EBP)-like element and was previously
      shown by Dnase I footprint analysis to bind to proteins in both rat liver and
      human hepatoma (HepG2) cell nuclear extracts. In this study, the importance of
      this region in the regulation of the UGT2B1 gene was assessed by functional and
      DNA binding assays. Varying lengths of the UGT2B1 gene promoter, with and without
      the C/EBP-like element, were fused to the chloramphenicol acetyltransferase
      reporter gene and transfected into HepG2 cells. Transcriptional activity of the
      UGT2B1 promoter construct containing the C/EBP-like element was strongly elevated
      in the presence of a cotransfected C/EBPalpha expression vector. In contrast, no
      change was observed when an expression vector encoding C/EBPbeta was
      cotransfected with the UGT2B1 promoter constructs. Introduction of point
      mutations into the C/EBP-like element prevented any C/EBPalpha-mediated increase
      in chloramphenicol acetyltransferase activity. Gel shift analyses demonstrated
      that the C/EBP-like element binds a complex of nuclear proteins present in both
      HepG2 cells and rat liver. The presence of C/EBPalpha in this complex was
      confirmed by supershift analysis with antiserum to this factor. These data
      strongly suggest that the liver-enriched factor C/EBPalpha binds to, and
      activates, the UGT2B1 gene promoter. The importance of C/EBPalpha in the
      regulation of the homologous mouse UGT2B1 gene was also assessed in vivo.
      Transcripts homologous to UGT2B1 were detected in the livers of mice containing
      intact c/ebpalpha and c/ebpbeta genes and in mice containing a homozygous null
      mutation in the c/ebpbeta gene. In contrast, these transcripts were not detected
      in mice with a disrupted hepatic c/ebpalpha gene. These data extend the findings
      with the rat UGT2B1 gene promoter and establish that C/EBPalpha, but not
      C/EBPbeta, is an essential transcriptional regulator of the homologous UGT2B1
      gene in the mouse.

PMID- 9614205
TI  - Selective inhibition of alpha1B-adrenergic receptor expression and function using
      a phosphorothioate antisense oligodeoxynucleotide.
AB  - To investigate alpha1B-adrenoceptor function, we developed a phosphorothioate
      antisense oligodeoxynucleotide (AO) to inhibit the expression of the alpha1B
      adrenoceptor subtype in DDT1 MF2 cells. We measured the cellular uptake of the AO
      and its effect on alpha1B-adrenoceptor mRNA expression, protein density, and
      coupling to phospholipase C. Cells treated with either a control
      oligodeoxynucleotide (CO) or medium alone served as control groups. Confocal
      microscopy demonstrated that DDT1 MF2 cells internalized carboxyfluorescein
      labeled (FAM) AO within 30 min. Analysis of cellular lysates showed that
      approximately 50% of the intracellular FAM-AO was present as an intact 18-mer for
      up to 48 hr. Incubation of cells with AO for 48 hr decreased alpha1B-adrenoceptor
      density ([3H]prazosin Bmax) versus control groups by 12% (1 microM AO) and 72%
      (10 microM AO). In time course experiments, AO (10 microM) reduced alpha1B
      adrenoceptor density by 28, 64, and 68% versus controls after 24, 48, and 72 hr
      of exposure, respectively. alpha1B-Adrenoceptor mRNA concentration (measured by
      RT-PCR) was reduced by 25% in cells treated for 48 hr with 10 microM AO versus
      controls. AO pretreatment (10 microM, 48 hr) reduced the maximum response to
      agonist-stimulated [3H]inositol phosphate accumulation. The maximal response of
      the full agonist norepinephrine was reduced by 30% after AO treatment, and by 73%
      for the partial agonist naphazoline. In contrast, AO did not affect histamine
      stimulated total [3H]inositol phosphate accumulation. Thus, AO effectively
      reduced alpha1B-adrenoceptor subtype expression and function in vitro, suggesting
      a potential to selectively inhibit alpha1B-adrenoceptor function in vivo.

PMID- 9614206
TI  - Characterization of human cellular gamma-glutamyl hydrolase.
AB  - A previously identified cDNA encoding a human gamma-glutamyl hydrolase was
      expressed in a baculovirus system. The expressed protein had molecular mass of 37
      kDa. Treatment of the protein with PNGase F produced a protein of molecular mass
      of 30 kDa, indicating that the protein contained asparagine-linked glycosylation.
      Sequence analysis of the expressed protein indicated that a 24-amino-acid signal
      peptide had been removed. A polyclonal antibody to the expressed enzyme was used
      in Western blot analysis of partially purified lysates of HL-60 promyeloid
      leukemia cells and MCF-7 breast cancer cells. The HL-60 and MCF-7 enzymes
      appeared as two closely spaced bands with a molecular mass of 37 kDa. Treatment
      of the HL-60 enzyme with PNGase F produced a protein with a molecular mass of 30
      kDa. The activities of the expressed enzyme and the enzyme from HL-60 cells were
      similar on methotrexate polyglutamates. Methotrexate-gamma-Glu is a poor
      substrate for the human enzyme relative to methotrexate gamma-Glu2-5. During
      hydrolysis of methotrexate-gamma-Glu4, all possible pterin-containing cleavage
      products (methotrexate and methotrexate-gamma-Glu1-3) appear. The results
      demonstrated that the human enzyme cleaves both the ultimate and penultimate
      gamma-linkages of methotrexate polyglutamates. Glutamate was released as either
      glutamic acid or gamma-Glu2. Longer chain species of gamma-Glun>2 were not
      observed. Inhibition by iodoacetic acid suggested that both the expressed enzyme
      and the HL-60 enzyme may contain a catalytically essential cysteine. These
      results indicate that the identified cDNA encodes the intracellular gamma
      glutamyl hydrolase found in a variety of human tumor cells and that the
      baculovirus-expressed enzyme is a suitable model for further structural and
      enzymatic studies.

PMID- 9614207
TI  - Contribution of phospholipase C-beta3 phosphorylation to the rapid attenuation of
      opioid-activated phosphoinositide response.
AB  - Activation of the delta-opioid receptor in NG108-15 neuroblastoma X glioma hybrid
      cells results in a transient increase at the intracellular level of inositol
      1,4,5-triphosphate [Ins(1,4,5)P3]. This time course in the transient increase in
      the Ins(1,4,5)P3 level is distinctly different from that observed in the
      homologous opioid receptor desensitization as measured by the inhibition of
      adenylyl cyclase activity. One probable mechanism for this rapid loss in
      Ins(1,4,5)P3 response is the feedback regulation of the phospholipase C activity.
      Regulation by protein phosphorylation was suggested by the observations that the
      opioid-mediated response was potentiated by calphostin C, an inhibitor of protein
      kinase C (PKC), and was abolished by either phorbol-12-myristate-13-acetate, a
      PKC activator, or calyculin A, a protein phosphatase1/2A inhibitor. The direct
      phosphorylation of phospholipase C was demonstrated by immunoprecipitation of PLC
      beta3 from metabolically labeled NG108-15 cells challenged with the delta
      selective agonist [D-Pen2, D-Pen5]enkephalin (DPDPE). A time- and DPDPE
      concentration-dependent and naloxone-reversible increase in the PLC-beta3
      phosphorylation can be demonstrated. This PLC-beta3 phosphorylation was mainly
      due to PKC activation because pretreatment of NG108-15 cells with calphostin C
      could block the DPDPE effect. Activation of the PLC-beta3 by DPDPE was one of the
      prerequisites for agonist-mediated PLC-beta3 phosphorylation because the
      aminosteroid phospholipase C inhibitor U73122 could block the DPDPE effect. In
      addition to DPDPE, lysophosphatidic acid (LPA) stimulated the PLC-beta3
      phosphorylation, but bradykinin did not. Furthermore, the LPA- and DPDPE-mediated
      PLC-beta3 phosphorylation was additive and was much less than that observed with
      phorbol-12-myristate-13-acetate. The effect of DPDPE was specific to PLC-beta3;
      the betagamma-insensitive phospholipase C-beta1 was not phosphorylated in the
      presence of either DPDPE or LPA. These results indicate that although PKC
      phosphorylation of PLC-beta3 is not obligatory for the opioid receptor
      desensitization, it seems to play a significant facilatory role in the mechanisms
      allowing desensitization of opioid-activated phospholipase C response before that
      of adenylyl cyclase inhibition.

PMID- 9614208
TI  - Evidence for the involvement of protein kinase C in the inhibition of prolactin
      gene expression by transforming growth factor-beta2.
AB  - We investigated the mechanisms by which transforming growth factor (TGF)-beta2
      inhibited prolactin mRNA expression in GH3 rat pituitary tumor cells. Maximal
      inhibition was observed with cells exposed to 5 ng/ml TGF-beta2 for 24 hr.
      Continuous presence of the hormone during the entire period was not necessary
      because exposure of cells to TGF-beta2 for 20 min was sufficient to trigger the
      same extent of prolactin mRNA inhibition at 24 hr as with its persistent
      presence. The action of TGF-beta2 could be abolished by cycloheximide or EGTA,
      suggesting the requirement of a newly synthesized protein and extracellular Ca2+.
      The response of prolactin mRNA to TGF-beta2 was inhibited by preincubation of
      cells with phorbol-12-myristate-13-acetate, which down-regulated protein kinase C
      (PKC). The activities of both the cytosolic and membrane PKC were significantly
      reduced at 20 min after TGF-beta2 addition, and inhibition continued to 24 hr,
      the last time point analyzed. However, the ratio of cytosolic to membrane PKC was
      not altered by TGF-beta2. Inhibition of PKC did not require the sustained
      presence of TGF-beta2. In vitro kinase assays of the immunoprecipitated PKC
      demonstrated that the activities of alpha, epsilon, mu, and zeta isozymes were
      significantly decreased in the TGF-beta2-treated cells, whereas that of PKClambda
      was not affected. Western blotting did not reveal any change in PKCepsilon steady
      state protein levels, suggesting TGF-beta2 inhibits PKC activity through a post
      translational mechanism. Our results support that inhibition of PKC activity is
      an early event mediating TGF-beta2-inhibited prolactin mRNA expression in GH3
      cells.

PMID- 9614209
TI  - Adenosine triphosphate-dependent transport of anionic conjugates by the rabbit
      multidrug resistance-associated protein Mrp2 expressed in insect cells.
AB  - The multidrug resistance-associated protein Mrp2 is expressed in liver, kidney,
      and small intestine and mediates ATP-dependent transport of conjugated organic
      anions across the apical membrane of epithelial cells. We recently cloned a
      rabbit cDNA encoding a protein that on basis of highest amino acid homology and
      tissue distribution was considered to be the rabbit homolog of rat Mrp2. To
      investigate whether rabbit Mrp2 mediates ATP-dependent transport similar to rat
      Mrp2, we expressed rabbit Mrp2 in Spodoptera frugiperda (Sf9) cells using
      recombinant baculovirus. Mrp2 was expressed as an underglycosylated protein in
      Sf9 cells and to a higher level compared with rabbit liver and renal proximal
      tubules. Both 17beta-estradiol-17-beta-D-glucuronide ([3H]E217betaG, 50 nM) and
      [3H]leukotriene C4 (3 nM) were taken up by Sf9-Mrp2 membrane vesicles in an ATP
      dependent fashion. Uptake of [3H]E217betaG was dependent on the osmolarity of the
      medium and saturable for ATP (Km = 623 microM). Leukotriene C4, MK571,
      phenolphthalein glucuronide, and fluorescein-methotrexate were good inhibitors of
      [3H]E217betaG transport. The inhibitory potency of cyclosporin A and methotrexate
      was moderate, whereas fluorescein, alpha-naphthyl-beta-D-glucuronide, and p
      nitrophenyl-beta-D-glucuronide did not inhibit transport. In conclusion, we show
      direct ATP-dependent transport by recombinant rabbit Mrp2 and provide new data on
      Mrp2 inhibitor specificity.

PMID- 9614210
TI  - Hepatic expression of multidrug resistance-associated protein-like proteins
      maintained in eisai hyperbilirubinemic rats.
AB  - The biliary excretion of several organic anions is mediated by the canalicular
      multispecific organic anion transporter (cMOAT), which is hereditarily defective
      in mutant rats such as Eisai hyperbilirubinemic rats (EHBR). In addition, using a
      kinetic study with isolated canalicular membrane vesicles, we recently suggested
      the presence of ATP-dependent organic anion transporter(s) other than cMOAT in
      EHBR [Pharm Res (NY) 12:1746-1755 (1995); J Pharmacol Exp Ther 282:866-872
      (1997)]. The aim of this study is to provide a molecular basis for the presence
      of multiplicity in the biliary excretion of organic anions in rats. Based on the
      homology with human multidrug resistance-associated protein (hMRP), two cDNA
      fragments encoding the carboxyl-terminal ATP-binding cassette region were
      amplified by reverse transcription-polymerase chain reaction from EHBR liver.
      These fragments exhibited approximately 70% amino acid identity with hMRP and rat
      cMOAT;, therefore, they were designated MRP-like proteins (MLP-1 and MLP-2). The
      cloned full length cDNA of MLP-1 and -2 from the Sprague-Dawley (SD) rat liver
      and colon cDNA library was composed of 1502 and 1523 amino acids, respectively,
      had the characteristics of ATP-binding cassette transporters, and exhibited
      homology with hMRP and rat cMOAT. Northern blot analysis indicated that MLP-1 is
      expressed predominantly in the liver in both SD rats and EHBR, whereas hepatic
      expression of MLP-2 was observed only in EHBR. In addition, MLP-2 was markedly
      induced by ligation of the bile duct in SD rat liver. In both SD rats and EHBR,
      MLP-2 was expressed predominantly in the duodenum, jejunum, and colon. These
      findings suggest that MLP-1 and MLP-2 might be novel members of the MRP family
      responsible for the excretion of organic anions from these epithelial cells, and
      that MLP-2 is an inducible one.

PMID- 9614211
TI  - Reactive oxygen species regulate macrophage scavenger receptor type I, but not
      type II, in the human monocytic cell line THP-1.
AB  - The uptake of modified low density lipoprotein via the macrophage scavenger
      receptor (MSR) results in the formation of lipid-laden foam cells during
      atherosclerosis. Because increased oxidative stress has been implicated in the
      pathogenesis of atherosclerosis, the role of reactive oxygen species on the
      activity and expression of MSR was investigated. The uptake of acetylated low
      density lipoprotein and the levels of MSR-I mRNA were inhibited by treatment with
      the oxygen radical scavengers 2,2,6, 6-tetramethylpiperidine-N-oxyl,
      dimethylthiourea or sodium benzoate, or the iron chelator deferoxamine.
      Dimethylthiourea or benzoate also decreased the levels of MSR-I mRNA in the
      presence of the transcription inhibitor actinomycin D. These results indicate
      that hydroxyl radicals produced from superoxide anions and hydrogen peroxide in
      the presence of free iron, contribute to an increased MSR activity by stabilizing
      MSR-I mRNA. Several sources of reactive oxygen species are involved as inhibition
      of MSR activity and levels of MSR-I mRNA occurred in the presence of rotenone, a
      mitochondrial complex I inhibitor, or acetovanillone, a NADPH oxidase inhibitor.
      The (oxidative) stress responsive nuclear factor kappaB is not involved as
      inhibitors of its activation remained without significant inhibition. In contrast
      to MSR-I, the levels of MSR-II mRNA, which is formed by alternative splicing of
      the same gene transcript, were largely unaffected by the inhibitors of reactive
      oxygen species formation and activity. The present results suggest that oxidant
      stress contributes to an increased activity of MSR by stabilizing MSR-I mRNA.

PMID- 9614212
TI  - Allosteric activation of the Ca2+ receptor expressed in Xenopus laevis oocytes by
      NPS 467 or NPS 568.
AB  - The Ca2+ receptor is a G protein-coupled receptor that enables parathyroid cells
      and certain other cells in the body to respond to changes in the concentration of
      extracellular Ca2+. In this study, two novel phenylalkylamine compounds, NPS 467
      and NPS 568, were examined for effects on Xenopus laevis oocytes expressing the
      bovine or human parathyroid Ca2+ receptors. Increases in chloride current (ICl)
      were elicited in oocytes expressing the bovine Ca2+ receptor when the
      extracellular Ca2+ concentration was raised above 1.5 mM, whereas Ca2+
      concentrations > 3 mM were generally necessary to elicit responses in oocytes
      expressing the human Ca2+ receptor. NPS 467 and NPS 568 potentiated the
      activation of ICl by extracellular Ca2+ in oocytes expressing either Ca2+
      receptor homolog, and this resulted in a leftward shift of the Ca2+ concentration
      response curve. Neither compound was active in the absence of extracellular Ca2+.
      Certain inorganic and organic cations known to activate the Ca2+ receptor were
      substituted for elevated levels of extracellular Ca2+ to increase ICl and the
      effects of these agonists were also potentiated by NPS 568 or NPS 467. The
      effects of NPS 568 were stereoselective and the R-enantiomer was about 10-fold
      more potent than the corresponding S-enantiomer. Neither NPS 467 nor 568 affected
      ICl in water-injected oocytes or in oocytes expressing the substance K receptor
      or the metabotropic glutamate receptor 1a. These results provide compelling
      evidence that NPS 467 and NPS 568 act directly upon the parathyroid Ca2+ receptor
      to increase its sensitivity to activation by extracellular Ca2+. This activity
      suggests that these compounds are positive allosteric modulators of the Ca2+
      receptor. As such, these compounds define a new class of pharmacological agents
      with potent and selective actions on the Ca2+ receptor.

PMID- 9614213
TI  - Kinetics of inhibition of rabbit reticulocyte peptidyltransferase by anisomycin
      and sparsomycin.
AB  - A detailed kinetic study was carried out on the inhibitory mechanisms of two
      eukaryotic peptidyltransferase drugs (I), anisomycin and sparsomycin. In an in
      vitro system from rabbit reticulocytes, AcPhe-puromycin is produced in a pseudo
      first-order reaction from the preformed AcPhe-tRNA/poly(U)/80S ribosome complex
      (complex C) and excess puromycin (S). This reaction is inhibited by anisomycin
      and sparsomycin through different mechanisms. Anisomycin acts as a mixed
      noncompetitive inhibitor. The product, AcPhe-puromycin, is derived only from C
      according to the puromycin reaction. On the other hand, sparsomycin reacts with
      complex C in a two-step reaction, [REACTION; SEE TEXT] An initial rapid binding
      of the drug produces the encounter complex CI. During this step and before
      conversion of CI to C*I, sparsomycin behaves as a competitive inhibitor. The
      rapidly produced CI is isomerized slowly to a conformationally altered species
      C*I in which I is bound more tightly. The rate constants of this step are k6 =
      2.1 min-1 and k7 = 0.095 min-1. Moreover, the low value of the association rate
      constant k7/Ki' (2 x 10(5) M-1 sec-1), provides insight into the rates of
      possible conformational changes occurring during protein synthesis and supports
      the proposal that sparsomycin is the first example of a slow-binding inhibitor of
      eukaryotic peptidyltransferase. When complex C is preincubated with
      concentrations of sparsomycin of >8 Ki and then reacts with a mixture of
      puromycin and sparsomycin, the inhibition becomes linear mixed noncompetitive and
      involves C*I instead of CI. During this phase, AcPhe-puromycin is produced from a
      new, modified ribosomal complex with a lower catalytic rate constant. Thus,
      sparsomycin also acts as a modifier of eukaryotic peptidyltransferase activity.

PMID- 9614214
TI  - Inhibition of human immunodeficiency virus type 1 replication and cytokine
      production by fluoroquinoline derivatives.
AB  - We have recently identified 8-difluoromethoxy-1-ethyl-6-fluoro-1, 4-dihydro-7-[4
      (2-methoxyphenyl)-1-piperazinyl]-4-oxoquinoline-3-carb oxylic acid (K-12) as a
      potent and selective inhibitor of human immunodeficiency virus type 1 (HIV-1)
      transcription. In the search for more effective derivatives and their mode of
      action, we have found 7-(3,4-dehydro-4-phenyl-1-piperidinyl)-1, 4-dihydro-6
      fluoro-1-methyl-8-trifluoromethyl-4-oxoquinoline-3- carboxylic acid (K-37) and 8
      difluoromethoxy-1,4-dihydro-6-fluoro-7-(3, 4-dehydro-4-phenyl-1-piperidinyl)1
      [4,(1,2, 4-triazol-1-yl)methylphenyl]-4-oxoquinoline-3-carboxylic acid (K-38) to
      be more potent inhibitors of HIV-1 replication than K-12. The EC50 values of K-37
      and K-38 for HIV-1IIIB were 27 and 3.8 nM in peripheral blood mononuclear cells,
      respectively. These values were approximately 3- and 24-fold lower than the EC50
      of K-12. K-38 was also a more potent inhibitor of HIV-1 replication in
      chronically infected cells, such as tumor necrosis factor alpha-stimulated OM-10.
      1 cells. K-37 and K-38 proved to be more cytotoxic than K-12 for a variety of
      cell lines as well as peripheral blood mononuclear cells. These compounds were
      more inhibitory of Tat-induced HIV-1 long terminal repeat-driven gene expression
      than K-12, which suggests that their mechanism of action is attributable in part
      to the inhibition of Tat function. Interestingly, K-37 and K-38 could suppress
      the production of tumor necrosis factor alpha and interleukin 6 in
      phytohemagglutinin-stimulated peripheral blood mononuclear cells and the
      expression of intercellular adhesion molecule 1 in tumor necrosis factor alpha
      stimulated human umbilical vein endothelial cells at their nontoxic
      concentrations. In contrast, another K-12 derivative, 1, 4-dihydro-8
      dimethylaminomethyl-6-fluoro-7-[4-(2-methoxyphenyl)-1-pip eradinyl]-1-methyl-4
      oxoquinoline-3-carboxylic acid (K-42), had anti-HIV-1 activity and cytotoxicity
      profiles similar to those of K-12, but K-42 scarcely inhibited the cytokine
      production and intercellular adhesion molecule 1 expression.

PMID- 9614215
TI  - Pharmacological properties of the T-type Ca2+ current of mouse spermatogenic
      cells.
AB  - The effects of pharmacological agents on the T-type Ca2+ current were studied in
      dissociated spermatogenic cells from the mouse. Ca2+ currents were elicited by
      depolarization in 10 mM Ca2+ and recorded in the whole-cell configuration of the
      patch clamp technique. The T-type current was inhibited by the following
      compounds: PN200-110 (IC50 = 4 x 10(-8) M) > nifedipine (IC50 = 4 x 10(-7) M) >
      pimozide (IC50 = 4.6 x 10(-7) M) > mibefradil (IC50 = 5 x 10(-6) M) > Ni2+ (IC50
      = 3.4 x 10(-5) M) > verapamil (IC50 = 7 x 10(-5) M) > amiloride (IC50 = 2.4 x 10(
      4) M) > Cd2+ (IC50 = 2.8 x 10(-4) M). However, the agents differed in the
      reversibility and the use dependence of their effects. Currents recovered rapidly
      and completely after removal of Ni2+, Cd2+, amiloride, or mibefradil, whereas
      recovery from verapamil block was rapid but incomplete. In contrast, we observed
      little recovery after the removal of pimozide and of the dihydropyridines (PN200
      110, nifedipine). Moreover, mibefradil and pimozide exhibit a strongly use
      dependent inhibition of current that is due to selective interaction of these
      drugs with the open state and the inactivated state of the channel, respectively,
      rather than with the resting state. These properties of the spermatogenic T-type
      Ca2+ channel differ from those of somatic cell T channels and suggest a molecular
      diversity of low voltage-activated Ca2+ channels.

PMID- 9614216
TI  - Glycosylation within the cysteine loop and six residues near conserved
      Cys192/Cys193 are determinants of neuronal bungarotoxin sensitivity on the
      neuronal nicotinic receptor alpha3 subunit.
AB  - Neuronal bungarotoxin (NBT) is a highly selective, slowly reversible, competitive
      antagonist of the alpha3beta2 neuronal nicotinic receptor. Contributions to NBT
      sensitivity are made by both the alpha3 and beta2 subunits. We used a chimeric
      alpha subunit to demonstrate that the entire alpha3 contribution lies within
      sequence segment 84-215. Construction and analysis of a series of mutant alpha3
      subunits identified seven amino acid residues (Thr143, Tyr184, Lys185, His186,
      Ile188, Gln198, Ser203) within this region that contribute to NBT sensitivity.
      Changing Thr143 to lysine, as in alpha2, resulted in a approximately 1000-fold
      loss of NBT sensitivity. The effect on NBT sensitivity of changing each of the
      other six residues ranged from 1.8- to 40.5-fold. More extensive mutagenesis
      demonstrated that Thr143 serves as part of the consensus sequence for
      glycosylation at N141, and it is this glycosylation that is the determinant of
      NBT sensitivity. Only serine could substitute for threonine to maintain full NBT
      sensitivity, and changing Asn141 to alanine resulted in a approximately 300-fold
      loss of NBT sensitivity. The chimera alpha2-181-alpha3, containing all identified
      determinants except the glycosylation site, formed receptors insensitive to 300
      nM NBT. Installation of threonine to complete the glycosylation consensus site in
      this chimera conferred NBT sensitivity only 10-fold less than that of wild-type
      alpha3beta2. These seven determinants of NBT sensitivity are located in close
      proximity to a series of conserved residues that are common features of all
      nicotinic receptor binding sites.

PMID- 9614217
TI  - On the unique binding and activating properties of xanomeline at the M1
      muscarinic acetylcholine receptor.
AB  - We investigated the molecular nature of the interaction between the functionally
      selective M1 muscarinic acetylcholine receptor (mAChR) agonist xanomeline and the
      human M1 mAChR expressed in Chinese hamster ovary (CHO) cells. In contrast to the
      non-subtype-selective agonist carbachol, xanomeline demonstrated M1 mAChR binding
      that was resistant to extensive washout, resulting in a significant reduction in
      apparent N-[3H]methylscopolamine saturation binding affinity in intact cells.
      Functional assays, using both M1 mAChR-mediated phosphoinositide hydrolysis and
      activation of neuronal nitric oxide synthase, confirmed that this persistent
      binding resulted in elevated basal levels of system activity. Furthermore, this
      phenomenon could be reversed by the addition of the antagonist atropine. However,
      pharmacological analysis of the inhibition by atropine of xanomeline-mediated
      functional responses indicated a possible element of noncompetitive behavior that
      was not evident in several kinetic and equilibrium binding experimental
      paradigms. Taken together, our findings indicate for the first time a novel mode
      of interaction between an mAChR agonist and the M1 mAChR, which may involve
      unusually avid binding of xanomeline to the receptor. This yields a fraction of
      added agonist that is retained at the level of the receptor compartment to
      persistently bind to and activate the receptor subsequent to washout. The results
      of the current study suggest that elucidation of the mechanism or mechanisms of
      interaction of xanomeline with the M1 mAChR is particularly important in relation
      to the potential therapeutic use of this agent in the treatment of Alzheimer's
      disease.

PMID- 9614218
TI  - Specific activation of the nuclear receptors PPARgamma and RORA by the
      antidiabetic thiazolidinedione BRL 49653 and the antiarthritic thiazolidinedione
      derivative CGP 52608.
AB  - The thiazolidinedione BRL 49653 and the thiazolidinedione derivative CGP 52608
      are lead compounds of two pharmacologically different classes of compounds. BRL
      49653 is a high affinity ligand of peroxisome proliferator-activated receptor
      gamma (PPARgamma) and a prototype of novel antidiabetic agents, whereas CGP 52608
      activates retinoic acid receptor-related orphan receptor alpha (RORA) and
      exhibits potent antiarthritic activity. Both receptors belong to the superfamily
      of nuclear receptors and are structurally related transcription factors. We
      tested BRL 49653 and CGP 52608 for receptor specificity on PPARgamma, RORA, and
      retinoic acid receptor alpha, a closely related receptor to RORA, and compared
      their pharmacological properties in in vitro and in vivo models in which these
      compounds have shown typical effects. BRL 49653 specifically induced PPARgamma
      mediated gene activation, whereas CGP 52608 specifically activated RORA in
      transiently transfected cells. Both compounds were active in nanomolar
      concentrations. Leptin production in differentiated adipocytes was inhibited by
      nanomolar concentrations of BRL 49653 but not by CGP 52608. BRL 49653 antagonized
      weight loss, elevated blood glucose levels, and elevated plasma triglyceride
      levels in an in vivo model of glucocorticoid-induced insulin resistance in rats,
      whereas CGP 52608 exhibited steroid-like effects on triglyceride levels and body
      weight in this model. In contrast, potent antiarthritic activity in rat adjuvant
      arthritis was shown for CGP 52608, whereas BRL 49653 was nearly inactive. Our
      results support the concept that transcriptional control mechanisms via the
      nuclear receptors PPARgamma and RORA are responsible at least in part for the
      different pharmacological properties of BRL 49653 and CGP 52608. Both compounds
      are prototypes of interesting novel therapeutic agents for the treatment of non
      insulin-dependent diabetes mellitus and rheumatoid arthritis.

PMID- 9614219
TI  - Gi- and protein kinase C-mediated heterologous potentiation of phospholipase C
      signaling by G protein-coupled receptors.
AB  - We recently reported that activation of the highly efficient phospholipase C
      (PLC) stimulatory m3 muscarinic acetylcholine receptor (mAChR) can induce a long
      lasting Gi-mediated heterologous potentiation of PLC stimulation in human
      embryonic kidney (HEK) 293 cells, which was accompanied by an increased cellular
      level of the PLC substrate phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)P2].
      Here, we examined whether such a potentiated PLC response is also induced by the
      rather poorly PLC stimulatory m2 mAChR and the endogenously expressed purinergic
      and lysophosphatidic acid receptors. Pretreatment of m2 mAChR-expressing HEK 293
      cells for 2 min with carbachol, followed by agonist washout and measurement of
      PLC activity >/=40 min later, caused a long-lasting (up to approximately 90 min)
      heterologous potentiation of receptor- and G protein-mediated PLC stimulation. A
      similar heterologous potentiation of receptor-mediated PLC stimulation was
      induced by short term activation of lysophosphatidic acid and purinergic
      receptors. Either of the three receptor agonists increased the cellular level of
      PtdIns(4,5)P2 by approximately 50%. The mAChR-induced PLC potentiation was fully
      prevented by either pertussis toxin or the protein kinase C (PKC) inhibitors
      staurosporine and Go 6976, which did not affect acute PLC stimulation. On the
      other hand, the rise in PtdIns(4,5)P2 was prevented only by combined treatment of
      HEK 293 cells with pertussis toxin and PKC inhibitors. In conclusion, we
      demonstrated that activation of poorly PLC stimulatory receptors can also induce
      a long-lasting Gi-mediated heterologous potentiation of PLC signaling in HEK 293
      cells and that this novel PLC regulatory process is under the control of PKC.

PMID- 9614220
TI  - Functional specialization and topographic segregation of hippocampal astrocytes.
AB  - Astrocytes have been suggested to play several roles in the complex control of
      brain microenvironment. However, they have been generally considered to
      constitute a homogeneous population of cells. Here we show that at least three
      electrophysiologically distinct types of astrocytes can be found in the mature
      hippocampus. These subpopulations of glia were characterized by expression of
      different ion currents. In astrocytes exposed to elevated K+, Cs+ prevented
      influx of K+ only in cells with inwardly rectifying currents (IIR). The
      topographic distribution of glia with Cs+-sensitive inward rectifying currents
      (involved in K+ buffering) was nonuniform. Cs+-sensitive astrocytes were
      predominantly found in CA3 radiatum, whereas most CA1 astrocytes were Cs+
      insensitive. Functional significance of the spatial segregation of glial cells
      with inward rectification was addressed in slices that were bathed in Cs+
      containing media. Under these conditions, neuronal stimulation induced
      spontaneous epileptiform activity, which first appeared in CA3 and was then
      synaptically propagated to CA1. Intracellular labeling of astrocytes with
      biocytin revealed that CA1 astrocytes are characterized by a high degree of cell
      to-cell coupling; in contrast, cell labeling in CA3 revealed smaller groups and
      occasionally individual cells. Three individual biocytin-labeled cells had
      electrophysiological properties indistinguishable from Cs+-sensitive astrocytes
      but had morphology typical of oligodendroglia. These results provide evidence for
      a role of K+ uptake via IIR into astrocytes. The segregated expression of
      potassium channels in a subpopulation of astrocytes suggests that functionally
      specialized cell types are involved in K+ homeostasis.

PMID- 9614221
TI  - Increased sensitivity to mitochondrial toxin-induced apoptosis in neural cells
      expressing mutant presenilin-1 is linked to perturbed calcium homeostasis and
      enhanced oxyradical production.
AB  - Many cases of autosomal dominant early onset Alzheimer's disease (AD) result from
      mutations in the gene encoding presenilin-1 (PS-1). PS-1 is an integral membrane
      protein expressed ubiquitously in neurons throughout the brain in which it is
      located primarily in endoplasmic reticulum (ER). Although the pathogenic
      mechanism of PS-1 mutations is unknown, recent findings suggest that PS mutations
      render neurons vulnerable to apoptosis. Because increasing evidence indicates
      that mitochondrial alterations contribute to neuronal death in AD, we tested the
      hypothesis that PS-1 mutations sensitize neurons to mitochondrial failure. PC12
      cell lines expressing a PS-1 mutation (L286V) exhibited increased sensitivity to
      apoptosis induced by 3-nitropropionic acid (3-NP) and malonate, inhibitors of
      succinate dehydrogenase, compared with control cell lines and lines
      overexpressing wild-type PS-1. The apoptosis-enhancing action of mutant PS-1 was
      prevented by antioxidants (propyl gallate and glutathione), zVAD-fmk, and
      cyclosporin A, indicating requirements of reactive oxygen species (ROS),
      caspases, and mitochondrial permeability transition in the cell death process. 3
      NP induced a rapid elevation of [Ca2+]i, which was followed by caspase
      activation, accumulation of ROS, and decreases in mitochondrial reducing
      potential and transmembrane potential in cells expressing mutant PS-1. The
      calcium chelator BAPTA AM and agents that block calcium release from ER and
      influx through voltage-dependent channels prevented mitochondrial ROS
      accumulation and membrane depolarization and apoptosis. Our data suggest that by
      perturbing subcellular calcium homeostasis presenilin mutations sensitize neurons
      to mitochondria-based forms of apoptosis that involve oxidative stress.

PMID- 9614222
TI  - beta-Amyloid fibrils activate parallel mitogen-activated protein kinase pathways
      in microglia and THP1 monocytes.
AB  - The senile plaques of Alzheimer's disease are foci of local inflammatory
      responses, as evidenced by the presence of acute phase proteins and oxidative
      damage. Fibrillar forms of beta-amyloid (Abeta), which are the primary
      constituents of senile plaques, have been shown to activate tyrosine kinase
      dependent signal transduction cascades, resulting in inflammatory responses in
      microglia. However, the downstream signaling pathways mediating Abeta-induced
      inflammatory events are not well characterized. We report that exposure of
      primary rat microglia and human THP1 monocytes to fibrillar Abeta results in the
      tyrosine kinase-dependent activation of two parallel signal transduction cascades
      involving members of the mitogen-activated protein kinase (MAPK) superfamily.
      Abeta stimulated the rapid, transient activation of extracellular signal
      regulated kinase 1 (ERK1) and ERK2 in microglia and ERK2 in THP1 monocytes. A
      second superfamily member, p38 MAPK, was also activated with similar kinetics.
      Scavenger receptor and receptor for advanced glycated end products (RAGE) ligands
      failed to activate ERK and p38 MAPK in the absence of significant increases in
      protein tyrosine phosphorylation, demonstrating that scavenger receptors and RAGE
      are not linked to these pathways. Importantly, the stress-activated protein
      kinases (SAPKs) were not significantly activated in response to Abeta. Downstream
      effectors of the MAPK signal transduction cascades include MAPKAP kinases, such
      as RSK1 and RSK2, as well as transcription factors. Exposure of microglia and
      THP1 monocytes to Abeta resulted in the activation of RSK1 and RSK2 and
      phosphorylation of cAMP response element-binding protein at Ser133, providing a
      mechanism for Abeta-induced changes in gene expression.

PMID- 9614223
TI  - Identification of four classes of brain nicotinic receptors using beta2 mutant
      mice.
AB  - Although the expression patterns of the neuronal nicotinic acetylcholine receptor
      (nAChR) subunits thus far described are known, the subunit composition of
      functional receptors in different brain areas is an ongoing question. Mice
      lacking the beta2 subunit of the nAChR were used for receptor autoradiography
      studies and patch-clamp recording in thin brain slices. Four distinct types of
      nAChRs were identified, expanding on an existing classification [Alkondon M,
      Albuquerque EX (1993) Diversity of nicotinic acetylcholine receptors in rat
      hippocampal neurons. I. Pharmacological and functional evidence for distinct
      structural subtypes. J Pharmacol Exp Ther 265:1455-1473.], and tentatively
      identifying the subunit composition of nAChRs in different brain regions. Type 1
      nAChRs bind alpha-bungarotoxin, are not altered in beta2 -/- mice, and contain
      the alpha7 subunit. Type 2 nAChRs contain the beta2 subunit because they are
      absent in beta2 -/- mice, bind all nicotinic agonists used with high affinity
      (excluding alpha-bungarotoxin), have an order of potency for nicotine >> cytisine
      in electrophysiological experiments, and are likely to be composed of alpha4
      beta2 in most brain regions, with other alpha subunits contributing in specific
      areas. Type 3 nAChRs bind epibatidine with high affinity in equilibrium binding
      experiments and show that cytisine is as effective as nicotine in
      electrophysiological experiments; their distribution and persistence in beta2 -/-
      mice strongly suggest a subunit composition of alpha3 beta4. Type 4 nAChRs bind
      cytisine and epibatidine with high affinity in equilibrium binding experiments
      and persist in beta2 -/- mice; cytisine = nicotine in electrophysiological
      experiments. Type 4 nAChRs also exhibit faster desensitization than type 3 nAChRs
      at high doses of nicotine. Knock-out animals lacking individual alpha subunits
      should allow a further dissection of nAChR subclasses.

PMID- 9614224
TI  - mu-Conotoxin PIIIA, a new peptide for discriminating among tetrodotoxin-sensitive
      Na channel subtypes.
AB  - We report the characterization of a new sodium channel blocker, mu-conotoxin
      PIIIA(mu-PIIIA). The peptide has been synthesized chemically and its disulfide
      bridging pattern determined. The structure of the new peptide is: [sequence: see
      text] where Z = pyroglutamate and O = 4-trans-hydroxyproline. We demonstrate that
      Arginine-14 (Arg14) is a key residue; substitution by alanine significantly
      decreases affinity and results in a toxin unable to block channel conductance
      completely. Thus, like all toxins that block at Site I, mu-PIIIA has a critical
      guanidinium group. This peptide is of exceptional interest because, unlike the
      previously characterized mu-conotoxin GIIIA (mu-GIIIA), it irreversibly blocks
      amphibian muscle Na channels, providing a useful tool for synaptic
      electrophysiology. Furthermore, the discovery of mu-PIIIA permits the resolution
      of tetrodotoxin-sensitive sodium channels into three categories: (1) sensitive to
      mu-PIIIA and mu-conotoxin GIIIA, (2) sensitive to mu-PIIIA but not to mu-GIIIA,
      and (3) resistant to mu-PIIIA and mu-GIIIA (examples in each category are
      skeletal muscle, rat brain Type II, and many mammalian CNS subtypes,
      respectively). Thus, mu-conotoxin PIIIA provides a key for further discriminating
      pharmacologically among different sodium channel subtypes.

PMID- 9614225
TI  - Altered calcium channel currents in Purkinje cells of the neurological mutant
      mouse leaner.
AB  - Mutations of the alpha1A calcium channel subunit have been shown to cause such
      human neurological diseases as familial hemiplegic migraine, episodic ataxia-2,
      and spinocerebellar ataxia 6 and also to cause the murine neurological phenotypes
      of tottering and leaner. The leaner phenotype is recessive and characterized by
      ataxia with cortical spike and wave discharges (similar to absence epilepsy in
      humans) and a gradual degeneration of cerebellar Purkinje and granule cells. The
      mutation responsible is a single-base substitution that produces truncation of
      the normal open reading frame beyond repeat IV and expression of a novel C
      terminal sequence. Here, we have used whole-cell recordings to determine whether
      the leaner mutation alters calcium channel currents in cerebellar Purkinje cells,
      both because these cells are profoundly affected in leaner mice and because they
      normally express high levels of alpha1A. In Purkinje cells from normal mice, 82%
      of the whole-cell current was blocked by 100 nM omega-agatoxin-IVA. In Purkinje
      cells from homozygous leaner mice, this omega-agatoxin-IVA-sensitive current was
      65% smaller than in control cells. Although attenuated, the omega-agatoxin-IVA
      sensitive current in homozygous leaner cells had properties indistinguishable
      from that of normal Purkinje neurons. Additionally, the omega-agatoxin-IVA
      insensitive current was unaffected in homozygous leaner mice. Thus, the leaner
      mutation selectively reduces P-type currents in Purkinje cells, and the alpha1A
      subunit and P-type current appear to be essential for normal cerebellar function.

PMID- 9614226
TI  - Neuronal expression of the glutamate transporter GLT-1 in hippocampal
      microcultures.
AB  - To address the question of the relative contributions of glial and neuronal
      glutamate transport in the vertebrate CNS, we studied the distribution of
      forebrain glutamate transporters in rat hippocampal microcultures, a preparation
      in which physiological functions of glutamate transporters have been well
      characterized. Two of the three transporters, GLAST (EAAT1) and EAAC1 (EAAT3),
      are localized to microculture glia and neurons, respectively, as expected.
      However, we find strong immunoreactivity for the third glutamate transporter GLT
      1 (EAAT2), a putatively glial transporter, in microculture neurons and in a small
      subset of microculture glia. Indistinguishable immunohistochemical staining
      patterns for GLT-1 were obtained with antibodies directed against both the N
      terminal and C terminal of the GLT-1 protein. Double-labeling experiments suggest
      that neuronal GLT-1 protein is primarily localized to the dendrites of excitatory
      neurons. Neuronal electrogenic transport currents in response to D-aspartate
      applications were occluded by the selective GLT-1 inhibitor dihydrokainate. In
      contrast, glia exhibited a larger transporter current density than did neurons,
      and the glial transport current was less sensitive to dihydrokainate. Neuronal
      transport currents were potentiated less than were glial currents when the
      chaotropic anion thiocyanate was substituted for gluconate in the whole-cell
      recording pipette, consistent with the previously reported lower anion
      permeability of EAAC1 and GLT-1 compared with that of GLAST. After microculture
      glia were rendered nonviable, excitatory autaptic currents (EACs) were prolonged
      in the presence of dihydrokainate, suggesting that neuronal GLT-1 is capable of
      participating in the clearance of synaptically released glutamate. Our results
      suggest that the initially proposed characterization of GLT-1 as a purely glial
      transporter is too simplistic and that under certain conditions functional GLT-1
      protein can be expressed in brain neurons. The study suggests that changes in GLT
      1 levels that occur with pathology or experimental manipulations cannot be
      assumed to be glial.

PMID- 9614227
TI  - Excitatory synaptic transmission in the inner retina: paired recordings of
      bipolar cells and neurons of the ganglion cell layer.
AB  - Properties of glutamatergic synaptic transmission were investigated by
      simultaneously voltage-clamping a pair of connected bipolar cells and cells in
      the ganglion cell layer (GLCs) in the newt retinal slice preparation. Activation
      of the Ca2+ current in a single bipolar cell was essential for evoking the
      glutamatergic postsynaptic current in the GLC. Depolarization for as short as 15
      msec activated both NMDA and non-NMDA receptors. On the other hand, analysis of
      the spontaneous glutamatergic synaptic currents of GLCs revealed that these
      currents consisted of mainly non-NMDA receptor activation with little
      contribution from NMDA receptors. This suggests that non-NMDA receptors of GLCs
      are clustered in postsynaptic membrane regions immediately beneath the release
      sites of bipolar cells and that NMDA receptors have lower accessibility to the
      released transmitter than non-NMDA receptors. Glutamate that is spilled over from
      the release sites may activate the NMDA receptors. When a prolonged depolarizing
      pulse was applied to a bipolar cell, the response induced by non-NMDA receptors
      was limited greatly by their fast desensitization, whereas NMDA receptors were
      able to produce a maintained response. The relationship between the pulse
      duration applied to the bipolar cell and the integrated charge of the response
      evoked in the GLC was almost linear. Therefore, we propose that both non-NMDA and
      NMDA receptors cooperate to transfer the graded photoresponses of bipolar cells
      proportionally to GLCs.

PMID- 9614228
TI  - Early onset photoreceptor abnormalities induced by targeted disruption of the
      interphotoreceptor retinoid-binding protein gene.
AB  - Vision in all vertebrates is dependent on an exchange of retinoids between the
      retinal pigment epithelium and the visual photoreceptors. It has been proposed
      that the interphotoreceptor retinoid-binding protein (IRBP) is essential for this
      intercellular exchange, and that it serves to prevent the potentially cytotoxic
      effects of retinoids. Although its precise function in vivo has yet to be
      defined, the early expression of IRBP suggests that it may also be required for
      normal photoreceptor development. To further assess the biological role of IRBP,
      we generated transgenic mice with targeted disruption of the IRBP gene (IRBP-/-
      mice). Specifically, homologous recombination was used to replace the first exon
      and promoter region of the IRBP gene with a phosphoglycerate kinase-promoted
      neomycin-resistant gene. Immunocytochemical and Western blot analyses
      demonstrated the absence of IRBP expression in the IRBP-/- mice. As early as
      postnatal day 11, histological examination of the retinas of IRBP-/- mice
      revealed a loss of photoreceptor nuclei and changes in the structural integrity
      of the receptor outer segments. At 30 d of age, the photoreceptor abnormalities
      in IRBP-/- mice were more severe, and electroretinographic recordings revealed a
      marked loss in photic sensitivity. In contrast, no morphological or
      electrophysiological changes were detected in age-matched heterozygotes. These
      observations indicate that normal photoreceptor development and function are
      highly dependent on the early expression of IRBP, and that in the absence of IRBP
      there is a slowly progressive degeneration of retinal photoreceptors.

PMID- 9614229
TI  - The alpha subunit of Gq contributes to muscarinic inhibition of the M-type
      potassium current in sympathetic neurons.
AB  - Rat superior cervical ganglion (SCG) neurons express low-threshold
      noninactivating M-type potassium channels (IK(M)), which can be inhibited by
      activation of M1 muscarinic receptors. This inhibition occurs via pertussis toxin
      insensitive G-proteins belonging to the Galphaq family (Caulfield et al., 1994 ).
      We have used DNA plasmids encoding antisense sequences against the 3'
      untranslated regions of Galpha subunits (antisense plasmids) to investigate the
      specific G-protein subunits involved in muscarinic inhibition of IK(M). These
      antisense plasmids specifically reduced levels of the target G-protein 48 hr
      after intranuclear injection. In cells depleted of Galphaq, muscarinic inhibition
      of IK(M) was attenuated compared both with uninjected neurons and with neurons
      injected with an inappropriate GalphaoA antisense plasmid. In contrast, depletion
      of Galpha11 protein did not alter IK(M) inhibition. To determine whether the
      alpha or beta gamma subunits of the G-protein mediated this inhibition, we have
      overexpressed the C terminus of beta adrenergic receptor kinase 1 (betaARK1),
      which binds free beta gamma subunits. betaARK1 did not reduce muscarinic
      inhibition of IK(M) at a concentration of plasmid that can reduce beta gamma
      mediated inhibition of calcium current (). Also, expression of beta1gamma2 dimers
      did not alter the IK(M) density in SCG neurons. In contrast, IK(M) was virtually
      abolished in cells expressing GTPase-deficient, constitutively active forms of
      Galphaq and Galpha11. These data suggest that Galphaq is the principal mediator
      of muscarinic IK(M) inhibition in rat SCG neurons and that this more likely
      results from an effect of the alpha subunit than the beta gamma subunits of the
      Gq heterotrimer.

PMID- 9614230
TI  - Multivesicular release at single functional synaptic sites in cerebellar stellate
      and basket cells.
AB  - The purpose of the present work was to test the hypothesis that no more than one
      vesicle of transmitter can be liberated by an action potential at a single
      release site. Spontaneous and evoked IPSCs were recorded from interneurons in the
      molecular layer of cerebellar slices. Evoked IPSCs were obtained using either
      extracellular stimulation or paired recordings of presynaptic and postsynaptic
      neurons. Connections were identified as single-site synapses when evoked current
      amplitudes could be grouped into one peak that was well separated from the
      background noise. Peak amplitudes ranged from 30 to 298 pA. Reducing the release
      probability by lowering the external Ca2+ concentration or adding Cd2+ failed to
      reveal smaller quantal components. Some spontaneous IPSCs (1.4-2.4%) and IPSCs
      evoked at single-site synapses (2-6%) were followed within <5 msec by a secondary
      IPSC that could not be accounted for by random occurrence of background IPSCs.
      Nonlinear summation of closely timed events indicated that they involved
      activation of a common set of receptors and therefore that several vesicles could
      be released at the same release site by one action potential. An average receptor
      occupancy of 0.70 was calculated after single release events. At some single-site
      connections, two closely spaced amplitude peaks were resolved, presumably
      reflecting single and double vesicular release. Consistent with multivesicular
      release, kinetics of onset, decay, and latency were correlated to IPSC amplitude.
      We conclude that the one-site, one-vesicle hypothesis does not hold at
      interneuron-interneuron synapses.

PMID- 9614231
TI  - A myosin III from Limulus eyes is a clock-regulated phosphoprotein.
AB  - The lateral eyes of the horseshoe crab Limulus polyphemus undergo dramatic daily
      changes in structure and function that lead to enhanced retinal sensitivity and
      responsiveness to light at night. These changes are controlled by a circadian
      neural input that alters photoreceptor and pigment cell shape, pigment migration,
      and phototransduction. Clock input to the eyes also regulates photomechanical
      movements within photoreceptors, including membrane shedding. The biochemical
      mechanisms underlying these diverse effects of the clock on the retina are
      unknown, but a major biochemical consequence of activating clock input to the
      eyes is a rise in the concentration of cAMP in photoreceptors and the
      phosphorylation of a 122 kDa visual system-specific protein. We have cloned and
      sequenced cDNA encoding the clock-regulated 122 kDa phosphoprotein and show here
      that it is a new member of the myosin III family. We report that Limulus myosin
      III is similar to other unconventional myosins in that it binds to calmodulin in
      the absence of Ca2+; it is novel in that it is phosphorylated within its myosin
      globular head, probably by cAMP-dependent protein kinase. The protein is present
      throughout the photoreceptor, including the region occupied by the photosensitive
      rhabdom. We propose that the phosphorylation of Limulus myosin III is involved in
      one or more of the structural and functional changes that occur in Limulus eyes
      in response to clock input.

PMID- 9614232
TI  - Odorant response properties of convergent olfactory receptor neurons.
AB  - Information about odorant stimuli is thought to be represented in spatial and
      temporal patterns of activity across neurons in the olfactory epithelium and the
      olfactory bulb (OB). Previous studies suggest that olfactory receptor neurons
      (ORNs) distributed in the nasal cavity project to localized regions in the
      glomerular layer of the OB. However, the functional significance of this
      convergence is not yet known, and in no studies have the odorant response
      properties of individual ORNs projecting to defined OB regions been measured
      directly. We have retrogradely labeled mouse ORNs connecting to different
      glomeruli in the dorsal OB and tested single cells for responses to odorants
      using fura-2 calcium imaging. ORNs that project to clusters of dorsomedial (DM)
      glomeruli exhibit different odorant response profiles from those that project to
      dorsolateral (DL) glomeruli. DL-projecting ORNs showed responses to compounds
      with widely different structures, including carvone, eugenol, cinnamaldehyde, and
      acetophenone. In contrast, DM-projecting neurons exhibited responses to a more
      structurally restricted set of compounds and responded preferentially to organic
      acids. These data demonstrate that ORN afferents segregate by odorant
      responsiveness and that the homogeneity of ORN and glomerular input varies with
      different OB regions. The data also demonstrate that a subpopulation of ORNs
      projecting to DM glomeruli is functionally similar.

PMID- 9614233
TI  - Changes in mitochondrial function resulting from synaptic activity in the rat
      hippocampal slice.
AB  - Digital imaging microfluorimetry was used to visualize changes in mitochondrial
      potential and intracellular Ca2+ concentration, [Ca2+]i, in thick slices of rat
      hippocampus. Electrical activity, especially stimulus train-induced bursting
      (STIB) activity, produced slow, prolonged changes in mitochondrial potential
      within hippocampal slices as revealed by fluorescence measurements with rhodamine
      dyes. Changes in mitochondrial potential showed both temporal and spatial
      correlations with the intensity of the electrical activity. Patterned changes in
      mitochondrial potential were observed to last from tens of seconds to minutes as
      the consequence of epileptiform discharges. STIB-associated elevations in [Ca2+]i
      were also prolonged and exhibited a spatial pattern similar to that of the
      mitochondrial depolarization. The mitochondrial depolarization was sensitive to
      TTX and glutamate receptor blockers ([Mg2+]o and CNQX or DNQX plus D-AP-5) and to
      the inhibition of glutamate release by activation of presynaptic NPY receptors.
      The monitoring of mitochondrial potential in slice preparations provides a new
      tool for mapping synaptic activity in the brain and for determining the roles of
      mitochondria in regulation of brain synaptic activity.

PMID- 9614234
TI  - Dopamine neurons make glutamatergic synapses in vitro.
AB  - Interactions between dopamine and glutamate play prominent roles in memory,
      addiction, and schizophrenia. Several lines of evidence have suggested that the
      ventral midbrain dopamine neurons that give rise to the major CNS dopaminergic
      projections may also be glutamatergic. To examine this possibility, we double
      immunostained ventral midbrain sections from rat and monkey for the dopamine
      synthetic enzyme tyrosine hydroxylase and for glutamate; we found that most
      dopamine neurons immunostained for glutamate, both in rat and monkey. We then
      used postnatal cell culture to examine individual dopamine neurons. Again, most
      dopamine neurons immunostained for glutamate; they were also immunoreactive for
      phosphate-activated glutaminase, the major source of neurotransmitter glutamate.
      Inhibition of glutaminase reduced glutamate staining. In single-cell
      microculture, dopamine neurons gave rise to varicosities immunoreactive for both
      tyrosine hydroxylase and glutamate and others immunoreactive mainly for
      glutamate, which were found near the cell body. At the ultrastructural level,
      dopamine neurons formed occasional dopaminergic varicosities with symmetric
      synaptic specializations, but they more commonly formed nondopaminergic
      varicosities with asymmetric synaptic specializations. Stimulation of individual
      dopamine neurons evoked a fast glutamatergic autaptic EPSC that showed
      presynaptic inhibition caused by concomitant dopamine release. Thus, dopamine
      neurons may exert rapid synaptic actions via their glutamatergic synapses and
      slower modulatory actions via their dopaminergic synapses. Together with evidence
      for glutamate cotransmission in serotonergic raphe neurons and noradrenergic
      locus coeruleus neurons, the present results suggest that glutamatergic
      cotransmission may be the rule for central monoaminergic neurons.

PMID- 9614235
TI  - Myosin Ibeta is located at tip link anchors in vestibular hair bundles.
AB  - Recent studies have suggested that myosin Ibeta mediates the adaptation of
      mechanoelectrical transduction in vestibular hair cells. An important prediction
      of this hypothesis is that myosin Ibeta should be found in the side insertional
      plaque, an osmiophilic hair bundle structure that anchors tip links and is
      thought to house the adaptation motor. To determine whether myosin Ibeta was
      situated properly to perform adaptation, we used immunofluorescence and
      immunoelectron microscopy with the monoclonal antibody mT2 to examine the
      distribution of myosin Ibeta in hair bundles of the bullfrog utricle. Although
      utricular hair cells differ in their rates and extent of adaptation [Baird RA
      (1994) Comparative transduction mechanisms of hair cells in the bullfrog
      utriculus. II. Sensitivity and response dynamics to hair bundle displacement. J
      Neurophysiol 71:685-705.], myosin Ibeta was present in all hair bundles,
      regardless of adaptation kinetics. Confirming that, nevertheless, it was
      positioned properly to mediate adaptation, myosin Ibeta was found at
      significantly higher levels in the side insertional plaque. Myosin Ibeta was also
      present at elevated levels at the second tip link anchor of a hair bundle, the
      tip insertional plaque, found at the tip of a stereocilium. These data support
      myosin Ibeta as the adaptation motor and are consistent with the suggestion that
      the motor serves to restore tension applied to transduction channels to an
      optimal level, albeit with different kinetics in different cell types.

PMID- 9614236
TI  - Involvement of distinct pioneer neurons in the formation of layer-specific
      connections in the hippocampus.
AB  - During neural development, specific recognition molecules provide the cues
      necessary for the formation of initial projection maps, which are reshaped later
      in development. In some systems, guiding cues for axonal pathfinding and target
      selection are provided by specific cells that are present only at critical times.
      For instance, the floor plate guides commissural axons in the spinal cord, and
      the subplate is involved in the formation of thalamocortical connections. Here we
      study the development of entorhinal and commissural connections to the murine
      hippocampus, which in the adult terminate in nonoverlapping layers. We show that
      two groups of pioneer neurons, Cajal-Retzius cells and GABAergic neurons, form
      layer-specific scaffolds that overlap with distinct hippocampal afferents at
      embryonic and early postnatal stages. Furthermore, at postnatal day 0 (P0)-P5,
      before the dendrites of pyramidal neurons develop, these pioneer neurons are
      preferential synaptic targets for hippocampal afferents. Birthdating analysis
      using 5'-bromodeoxyuridine (BrdU) pulses showed that most such early-generated
      neurons disappear at late postnatal stages, most likely by cell death. Together
      with previous studies, these findings indicate that distinct pioneer neurons are
      involved in the guidance and targeting of different hippocampal afferents.

PMID- 9614237
TI  - Purification and characterization of adult oligodendrocyte precursor cells from
      the rat optic nerve.
AB  - Oligodendrocyte precursor cells (OPCs) persist in substantial numbers in the
      adult brain in a quiescent state suggesting that they may provide a source of new
      oligodendrocytes after injury. To determine whether adult OPCs have the capacity
      to divide rapidly, we have developed a method to highly purify OPCs from adult
      optic nerve and have directly compared their properties with their perinatal
      counterparts. When cultured in platelet-derived growth factor (PDGF), an
      astrocyte-derived mitogen, perinatal OPCs divided approximately once per day,
      whereas adult OPCs divided only once every 3 or 4 d. The proliferation rate of
      adult OPCs was not increased by addition of fibroblast growth factor (FGF) or of
      the neuregulin glial growth factor 2 (GGF2), two mitogens that are normally
      produced by retinal ganglion cells. cAMP elevation has been shown previously to
      be essential for Schwann cells to survive and divide in response to GGF2 and
      other mitogens. Similarly we found that when cAMP levels were elevated, GGF2
      alone was sufficient to induce perinatal OPCs to divide slowly, approximately
      once every 4 d, but adult OPCs still did not divide. When PDGF was combined with
      GGF2 and cAMP elevation, however, the adult OPCs began to divide rapidly. These
      findings indicate that adult OPCs are intrinsically different than perinatal
      OPCs. They are not senescent cells, however, because they retain the capacity to
      divide rapidly. Thus, after demyelinating injuries, enhanced axonal release of
      GGF2 or a related neuregulin might collaborate with astrocyte-derived PDGF to
      induce rapid division of adult OPCs.

PMID- 9614238
TI  - On the role of voltage-dependent calcium channels in calcium signaling of
      astrocytes in situ.
AB  - Calcium ions play crucial roles in a large variety of cell functions. The recent
      proposal that changes in the intracellular calcium concentration ([Ca2+]i) in
      astrocytes underline a reciprocal communication system between neurons and
      astrocytes encourages the interest in the definition of the various components
      participating in this novel Ca2+ signaling system. We investigate here whether
      functional voltage-operated calcium channels (Ca2+ VOCs), which are clearly
      expressed in cultured astrocytes, participate in the regulation of [Ca2+]i also
      in astrocytes in situ. Depolarization with 40-60 mM K+ was used to analyze the
      activity of Ca2+ VOCs in Indo-1-loaded astrocytes in acute slices from the visual
      cortex and the CA1 hippocampal region of developing rats. We demonstrate here
      that the depolarization-induced [Ca2+]i increases in astrocytes are solely
      attributed to the activation of metabotropic receptors by neurotransmitters, such
      as glutamate, released by synaptic terminals on depolarization. In fact, (1) the
      K+-induced [Ca2+]i increases in astrocyte [Ca2+]i were potently reduced by alpha
      methyl-4-carboxyphenylglycine, a metabotropic glutamate receptor competitive
      inhibitor; (2) after emptying intracellular Ca2+ stores with cyclopiazonic acid,
      none of the astrocytes displayed a [Ca2+]i increase on the depolarizing stimulus;
      and (3) after inhibiting neurotransmitter secretion in neurons by incubating the
      slices with tetanus neurotoxin, no [Ca2+]i increase on K+ stimulation was
      observed in astrocytes. Finally, patch-clamp whole-cell recordings from
      hippocampal astrocytes in acute brain slices failed to reveal any voltage
      dependent calcium currents. On the basis of these results, the various roles
      proposed for astrocyte Ca2+ VOCs in the CNS should be reconsidered.

PMID- 9614239
TI  - A developmental shift from GABAergic to glycinergic transmission in the central
      auditory system.
AB  - GABAergic and glycinergic circuits are found throughout the auditory brainstem,
      and it is generally assumed that transmitter phenotype is established early in
      development. The present study documents a profound transition from GABAergic to
      glycinergic transmission in the gerbil lateral superior olive (LSO) during the
      first 2 postnatal weeks. Whole-cell voltage-clamp recordings were obtained from
      LSO neurons in a brain slice preparation, and IPSCs were evoked by electrical
      stimulation of the medial nucleus of the trapezoid body (MNTB), a known
      glycinergic projection in adult animals. GABAergic and glycinergic components
      were identified by blocking transmission with bicuculline and strychnine (SN),
      respectively. In the medial limb of LSO, there was a dramatic change in the
      GABAergic IPSC component, decreasing from 78% at postnatal day 3 (P3)-P5 to 12%
      at P12-P16. There was an equal and opposite increase in the glycinergic component
      during this same period. Direct application of GABA also elicited significantly
      larger amplitude and longer duration responses in P3-P5 neurons compared with
      glycine-evoked responses. In contrast, MNTB-evoked IPSCs in lateral limb neurons
      were more sensitive to SN throughout development. Consistent with the
      electrophysiological observations, there was a reduction in staining for the
      beta2,3-GABAA receptor subunit from P4 to P14, whereas staining for the glycine
      receptor-associated protein gephyrin increased. Brief exposure to baclofen
      depressed transmission at excitatory and inhibitory synapses for approximately 15
      min, suggesting a GABAB-mediated metabotropic signal. Collectively, these data
      demonstrate a striking switch from GABAergic to glycinergic transmission during
      postnatal development. Although GABA and glycine elicit similar postsynaptic
      ionotropic responses, our results raise the possibility that GABAergic
      transmission in neonates may play a developmental role distinct from that of
      glycine.

PMID- 9614240
TI  - Inhibition of CPP32-like proteases rescues axotomized retinal ganglion cells from
      secondary cell death in vivo.
AB  - The majority of retinal ganglion cells (RGCs) degenerate and die after
      transection of the optic nerve (ON) in the adult rat. This secondary cell death
      can primarily be ascribed to apoptosis. Recent work strongly suggests a decisive
      role for a family of cysteine proteases, termed caspases, as mediators of
      neuronal apoptosis. In this study, we investigated whether activation of caspases
      contributes to delayed death of RGCs after axotomy. Intraocular application of
      various caspase inhibitors rescued up to 34% of RGCs that would otherwise have
      died 14 d after ON transection. Using a modified affinity-labeling technique, we
      detected a 17 kDa protease subunit upregulated after axotomy. Upregulation was
      prevented by caspase inhibitor treatment. The 17 kDa protein was identified as a
      CPP32-like protease by Western blot analysis and affinity labeling with
      biotinylated acetyl-Asp-Glu-Val-Asp-aldehyde, which specifically inhibits CPP32
      like caspases. In vivo application of the irreversible caspase inhibitor
      benzyloxycarbonyl-Asp-Glu-Val-Asp-chloromethylketone revealed CPP32-like
      proteases to be major mediators of caspase-induced apoptosis in axotomized RGCs,
      because this inhibitor showed an even higher neuroprotective potential than the
      irreversible wide-range inhibitor benzyloxycarbonyl-Val-Ala-DL-Asp
      fluoromethylketone. In summary, the data presented here provide further insight
      into the mechanisms of injury-induced neuronal apoptosis and could give rise to
      more effective therapeutic intervention strategies in CNS trauma and
      neurodegenerative diseases.

PMID- 9614241
TI  - Dual action of a ligand for Eph receptor tyrosine kinases on specific populations
      of axons during the development of cortical circuits.
AB  - The structural basis of cortical columns are radially oriented axon collaterals
      that form precise connections between distinct cortical layers. During
      development, these connections are highly specified from the initial outgrowth of
      collateral branches. Our previous work provided evidence for positional cues
      confined to individual layers that induce and/or prevent the formation of axon
      collaterals in specific populations of cortical neurons. Here we demonstrated
      with in situ hybridization techniques that mRNA of the Eph receptor tyrosine
      kinase EphA5 and one of its ligands, ephrin-A5, are present in distinct cortical
      layers, at a time when intrinsic connections are being formed in the cortex.
      Axonal guidance assays indicate that ephrin-A5 is a repellent signal for a
      populations of axons that in vivo avoid the cortical layer expressing ephrin-A5.
      In contrast to its established role as a repulsive axonal guidance signal, ephrin
      A5 specifically mediates sprouting of those cortical axons that target the ephrin
      A5-expressing layer in vivo. These results identify a novel function of ephrin-A5
      on axonal arbor formation. The laminar distribution and the dual action on
      specific populations of axons suggest that ephrin-A5 plays a role in the assembly
      of local cortical circuits.

PMID- 9614242
TI  - Electrophysiological development of central neurons in the Drosophila embryo.
AB  - In this study, we describe the development of electrical properties of Drosophila
      embryonic central neurons in vivo. Using whole-cell voltage clamp, we describe
      the onset of expression of specific voltage- and ligand-gated ionic currents and
      the first appearance of endogenous and synaptic activity. The first currents
      occur during midembryogenesis [late stage 16, 13-14 hr after egg laying (AEL)]
      and consist of a delayed outward potassium current (IK) and an acetylcholine
      gated inward cation current (IACh). As development proceeds, other voltage
      activated currents arise sequentially. An inward calcium current (ICa) is first
      observed at 15 hr AEL, an inward sodium current (INa) at 16 hr AEL, and a rapidly
      inactivating outward potassium current (IA) at 17 hr AEL. The inward calcium
      current is composed of at least two individual and separable components that
      exhibit small temporal differences in their development. Endogenous activity is
      first apparent at 15 hr AEL and consists of small events (peak amplitude, 5 pA)
      that probably result from the random opening of relatively few numbers of ion
      channels. At 16 hr AEL, discrete (10-15 msec duration) currents that exhibit
      larger amplitude (25 pA maximum) and rapid activation but slower inactivation
      first appear. We identify these latter currents as EPSCs, an indication that
      functional synaptic transmission is occurring. In the neurons from which we
      record, action potentials first occur at 17 hr AEL. This study is the first to
      record from Drosophila embryonic central neurons in vivo and makes possible
      future work to define the factors that shape the electrical properties of neurons
      during development.

PMID- 9614243
TI  - Expression of GDNF family receptor components during development: implications in
      the mechanisms of interaction.
AB  - Glial cell line-derived neurotrophic factor (GDNF) and a related factor,
      neurturin, promote survival of diverse groups of neurons. Both GDNF and neurturin
      signal via a two-component receptor complex that consists of a ligand-binding
      GDNF family receptor (GFRalpha-1 or GFRalpha-2) and the receptor protein tyrosine
      kinase Ret. Recently, a third receptor related to GFRalpha-1 and GFRalpha-2 has
      also been isolated and designated GFRalpha-3. Although much is known about the
      interaction among GDNF family factors, Ret, and the alpha-receptors in vitro, it
      remains unclear about their interactions in vivo. We show here by in situ
      hybridization that Ret and the alpha-receptors may be colocalized in the same
      tissues or expressed separately in projecting and target tissues, respectively,
      indicating that two distinct modes of interaction between Ret and the alpha
      receptors exist in vivo. First, Ret may interact with the alpha-receptors
      expressed in the same cells (termed interaction "in cis") in many tissues and
      cell populations that respond to GDNF and/or neurturin, such as the substantia
      nigra, dorsal root ganglia, spinal cord motoneurons, kidney, and intestine.
      Second, Ret may interact with the alpha-receptors localized in the target neurons
      (termed interaction "in trans"). In addition, we present evidence in vitro that
      GFRalpha-1 mediates Ret activation by GDNF in trans. These observations suggest
      that there are multiple mechanisms regulating the interaction between Ret and the
      alpha-receptors that mediates the effects of GDNF family trophic factors on the
      survival and differentiation of cells and on neuron-target interactions in the
      nervous system.

PMID- 9614244
TI  - Neural response during preference and memory judgments for subliminally presented
      stimuli: a functional neuroimaging study.
AB  - Preexposing subjects to visual stimuli is sufficient to establish a subsequent
      preference, even when previous exposure is subliminal, such that explicit
      recognition is at chance. This influence of previous exposure on preference
      judgments, known as the "mere exposure effect," is a form of unconscious memory.
      The present functional neuroimaging study examines the mechanism of this effect.
      Nine volunteer subjects were studied using functional imaging while making forced
      choice judgments about abstract stimuli on the basis of either preference or
      memory. Each judgment type was made under two conditions: under one condition one
      or the other stimulus had previously been presented subliminally, whereas under
      the second condition both stimuli were novel. Memory judgments were associated
      with activation of left frontopolar cortex and parietal areas, whereas preference
      judgments were associated with activation of medial prefrontal cortex and regions
      of occipital cortex. The modulation of preference by objective familiarity
      (implicit memory) was associated with right lateral frontal activation.
      Significant activation of hippocampal gyrus was seen in response to objective
      stimulus novelty, regardless of judgment type required. Our data thus demonstrate
      activations of a memory system independent of recollective experience.
      Dissociable activations within this system implicate a frontopolar involvement in
      explicit retrieval attempt and right lateral prefrontal cortex involvement in
      implicit memory expressed in preference judgments. Furthermore, the results
      suggest that hippocampal response to stimulus novelty can be independent of
      conscious reportability of familiarity.

PMID- 9614245
TI  - Innervation of histaminergic tuberomammillary neurons by GABAergic and
      galaninergic neurons in the ventrolateral preoptic nucleus of the rat.
AB  - The tuberomammillary nucleus (TMN) is the major source of histaminergic
      innervation of the mammalian brain and is thought to play a major role in
      regulating wake-sleep states. We recently found that sleep-active neurons in the
      ventrolateral preoptic nucleus (VLPO) provide a major input to the TMN, but the
      specificity of this projection and the neurotransmitters involved remain unknown.
      In this study, we examined the relationship of VLPO efferents to the TMN using
      both retrograde and anterograde tracing, combined with immunocytochemistry. We
      found that the descending projection from the VLPO selectively targets the cell
      bodies and proximal dendrites of the histaminergic TMN. In addition, VLPO axons
      could be traced into the brainstem, where they provided terminals in the the
      serotoninergic dorsal and median raphe nuclei, and the core of the noradrenergic
      locus coeruleus. Approximately 80% of the VLPO neurons that were retrogradely
      labeled by tracer injections including the TMN were immunoreactive either for
      galanin or for glutamic acid decarboxylase (GAD), the synthetic enzyme for GABA.
      Virtually all of the galaninergic neurons in the VLPO were also GAD positive. Our
      results indicate that the VLPO may provide inhibitory GABAergic and galaninergic
      inputs to the cell bodies and proximal dendrites of the TMN and other components
      of the ascending monoaminergic arousal system. Because these cell groups are
      simultaneously inhibited during sleep, the VLPO sleep-active neurons may play a
      key role in silencing the ascending monoaminergic arousal system during sleep.

PMID- 9614246
TI  - Connectivity and convergence of single corticostriatal axons.
AB  - The distribution of synapses formed by corticostriatal neurons was measured to
      determine the average connectivity and degree of convergence of these neurons and
      to search for spatial inhomogeneities. Two kinds of axonal fields, focal and
      extended, and two striatal tissue compartments, the patch (striosome) and matrix,
      were analyzed separately. Electron microscopic examination revealed that both
      kinds of corticostriatal axons made synapses at varicosities that could be
      identified in the light microscope, and each varicosity made a single synapse.
      Thus, the distribution of varicosities was a good estimate of the spatial
      distribution of synapses. The distance between axonal varicosities was measured
      to determine the density of synaptic connections formed by one axon within the
      volume occupied by a striatal neuron. Intersynaptic distances were distributed
      exponentially, except that synapses were rarely located <4 microm apart. The mean
      distance between synapses was approximately 10 microm, so axons made a maximum of
      40 synapses within the dendritic volume of a spiny neuron. There are
      approximately 2840 spiny neurons located within the volume of the dendrites of
      one spiny cell (Oorschot, 1996), so each axon must contact </=1.4% of all cells
      in its axonal arborization. Within the same volume there are approximately 30.5
      million asymmetric synapses (Ingham et al., 1996), approximately half of which
      are cortical in origin. Thus, approximately 380,000 cortical axons innervate the
      volume of the dendritic tree of one spiny cell. Striatal neurons with totally
      overlapping dendritic volumes have few presynaptic cortical axons in common, and
      cortical cells with overlapping axons have few striatal target neurons in common.
      These results explain the absence of redundancy in the responses of neurons
      located near each other in the striatum.

PMID- 9614247
TI  - Plasticity of synapses in the rat neostriatum after unilateral lesion of the
      nigrostriatal dopaminergic pathway.
AB  - In the 6-hydroxydopamine model of Parkinson's disease in the rat, there is a
      significant reduction in the number of dendritic spines on the principal
      projection neurons in the neostriatum, presumably attributable to loss of the
      nigrostriatal dopamine input. These spines invariably receive input from
      terminals forming asymmetric synapses that originate mainly from the cortex. The
      object of the present study was to determine the fate of those terminals after
      the loss of dendritic spines. Unbiased estimates of synaptic density and absolute
      numbers of synapses in a defined volume of the neostriatum were made using the
      "disector" and Cavalieri techniques. Numerical synaptic density of asymmetric
      synaptic contacts was 17% lower in the neostriatum deprived of dopamine
      innervation and, in absolute terms, there were 3 billion (19%) fewer contacts.
      The numerical density of a subpopulation of asymmetric contacts on dendritic
      spines that have complex or perforated synaptic specializations and normally make
      up 9% of the asymmetric population was 44% higher on the experimental side.
      Asymmetric synapses were found to be enriched in glutamate using postembedding
      immunogold labeling. The present observations demonstrate that the loss of spines
      previously reported after 6-hydroxydopamine lesions is accompanied by a loss of
      asymmetric synapses rather than by the movement of synapses from spines to other
      postsynaptic targets. The study also demonstrates that there is an increase in
      complex synaptic interactions that have been implicated in synaptic plasticity in
      other regions of the CNS after experimental manipulations.

PMID- 9614248
TI  - Functional recovery and enhanced corticofugal plasticity after unilateral
      pyramidal tract lesion and blockade of myelin-associated neurite growth
      inhibitors in adult rats.
AB  - After a lesion of the mature CNS, structural plasticity and functional recovery
      are very limited, in contrast to the developing CNS. The postnatal decrease in
      plasticity is correlated in time with the formation of myelin. To investigate the
      possible role of an important myelin-associated neurite growth inhibitor (NI-250;
      IN-1 antigen), one pyramidal tract of adult Lewis rats was lesioned
      (pyramidotomy), and the rats were treated with the antibody IN-1, a control
      antibody, or no antibody. Functional recovery was studied from postoperative day
      14 until day 42 using a food pellet reaching task, rope climbing, and a grid walk
      paradigm. The corticofugal projections to the red nucleus and basilar pontine
      nuclei were analyzed after survival times of 2 and 16 weeks. Treatment with the
      monoclonal antibody IN-1 resulted in almost complete restoration of skilled
      forelimb use, whereas all the control groups showed severe and chronic
      impairments. This functional recovery was paralleled by sprouting of the
      corticorubral and the corticopontine fibers across the midline, thus establishing
      a bilateral, anatomically specific projection.

PMID- 9614249
TI  - Aversive and appetitive events evoke the release of corticotropin-releasing
      hormone and bombesin-like peptides at the central nucleus of the amygdala.
AB  - There is wide agreement that corticotropin-releasing hormone (CRH) systems within
      the brain are activated by stressful stimuli. There is also mounting evidence for
      the role of bombesin (BN)-like peptides in the mediation of the stress response.
      To date, however, the extent to which other stimuli increase the activity of
      these peptidergic systems has received little attention. In the present
      investigation we validated and used in vivo microdialysis sampling followed by ex
      vivo radioimmunoassays to monitor the release of CRH and BN-like peptides during
      appetitive (food intake) and stressful (restraint) events. It is demonstrated for
      the first time that the in vivo release of CRH and BN-like peptides at the
      central nucleus of the amygdala was markedly increased by both stressor exposure
      and food ingestion. In fact, the meal-elicited rise of CRH release was as great
      as that associated with 20 min of restraint stress. Paralleling these findings,
      circulating ACTH and corticosterone levels were also increased in response to
      both food intake and restraint. Contrary to the current views, these results
      indicate that either food ingestion is interpreted as a "stressful" event by
      certain neural circuits involving the central amygdala or that the CRH- and BN
      related peptidergic systems may serve a much broader role than previously
      envisioned. Rather than evoking feelings of fear and anxiety, these systems may
      serve to draw attention to events or cues of biological significance, such as
      those associated with food availability as well as those posing a threat to
      survival.

PMID- 9614250
TI  - Aging alters the rhythmic expression of vasoactive intestinal polypeptide mRNA
      but not arginine vasopressin mRNA in the suprachiasmatic nuclei of female rats.
AB  - Our laboratory has shown that the ability of the suprachiasmatic nuclei (SCN) to
      regulate a number of rhythmic processes may be compromised by the time females
      reach middle age. Therefore, we examined the effects of aging on the rhythmic
      expression of two neuropeptides synthesized in the SCN, vasoactive intestinal
      polypeptide (VIP) and arginine vasopressin (AVP), using in situ hybridization.
      Because both VIP and AVP are outputs of the SCN, we hypothesized that age-related
      changes in rhythmicity are associated with alterations in the patterns of
      expression of these peptides. We found that VIP mRNA levels exhibited a 24 hr
      rhythm in young females, but by the time animals were middle-aged, this rhythm
      was gone. The attenuation of rhythmicity was associated with a decline in the
      level of mRNA per cell and in the number of cells in the SCN producing detectable
      VIP mRNA. AVP mRNA also showed a robust 24 hr rhythm in young females. However,
      in contrast to VIP, the AVP rhythm was not altered in the aging animals. The
      amount of mRNA per cell and the number of cells expressing AVP mRNA also was not
      affected with age. Based on these results we conclude that (1) various components
      of the SCN are differentially affected by aging; and (2) age-related changes in
      various rhythms may be attributable to changes in the ability of the SCN to
      transmit timing information to target sites. This may explain why the
      deterioration of various rhythmic processes occurs at different rates and at
      different times during the aging process.

PMID- 9614251
TI  - Circadian rhythms of rod-cone dominance in the Japanese quail retina.
AB  - When the Japanese quail is held in constant darkness, retinal responses (ERG b
      waves) increase during the animal's subjective night and decrease during its
      subjective day. Rod photoreceptors dominate the b-wave responses (lambdamax = 506
      nm) to all stimulus intensities at night but only to those intensities below the
      cone threshold during the day. Above the cone threshold, cones dominate b-wave
      responses (lambdamax, approximately 550-600 nm) during the day regardless of the
      state of retinal adaptation. Apparently a circadian oscillator enables cone
      signals to block rod signals during the day but not at night. The ERG b-wave
      reflects the activity of bipolar cells that are postsynaptic to rods and cones.
      The ERG a-wave reflects the activity of both rods and cones. The amplitude of the
      isolated a-wave (PIII) changes with time of day, as does that of the b-wave, but
      its spectral sensitivity does not. The PIII responses are maximal at
      approximately 520 nm both day and night and may reflect multiple receptor
      mechanisms. The shift in rod-cone dominance detected with the ERG b-wave
      resembles the Purkinje shift of human vision but, unlike the Purkinje shift, does
      not require a change in ambient light intensity. The shift occurs in constant
      darkness, with a period of approximately 24 hr indicative of a circadian rhythm
      in the functional organization of the retina.

PMID- 9614252
TI  - Synaptic depression and the temporal response characteristics of V1 cells.
AB  - We explore the effects of short-term synaptic depression on the temporal dynamics
      of V1 responses to visual images by constructing a model simple cell. Synaptic
      depression is modeled on the basis of previous detailed fits to experimental
      data. A component of synaptic depression operating in the range of hundreds of
      milliseconds can account for a number of the unique temporal characteristics of
      cortical neurons, including the bandpass nature of frequency-response curves,
      increases in response amplitude and in cutoff frequency for transient stimuli,
      nonlinear temporal summation, and contrast-dependent shifts in response phase.
      Synaptic depression also provides a mechanism for generating the temporal phase
      shifts needed to produce direction selectivity, and a model constructed along
      these lines matches both extracellular and intracellular data. A slower component
      of depression can reproduce the effects of contrast adaptation.

PMID- 9614253
TI  - Substance P modulates NMDA responses and causes long-term protein synthesis
      dependent modulation of the lamprey locomotor network.
AB  - Tachykinin immunoreactivity is found in a ventromedial spinal plexus in the
      lamprey. Neurons in this plexus project bilaterally and are thus in a position to
      modulate locomotor networks on both sides of the spinal cord. We have examined
      the effects of the tachykinin substance P on NMDA-evoked locomotor activity.
      Brief (10 min) application of tachykinin neuropeptides results in a prolonged
      concentration-dependent (>24 hr) modulation of locomotor activity, shown by the
      increased burst frequency and more regular burst activity. These effects are
      blocked by the tachykinin antagonist spantide II. There are at least two phases
      to the burst frequency modulation. An initial phase (approximately 2 hr) is
      associated with the protein kinase C-dependent potentiation of cellular responses
      to NMDA. The long-lasting phase (>2 hr) appears to be protein synthesis
      dependent, with protein synthesis inhibitors causing the increased burst
      frequency to recover after washing for 2-3 hr. The modulation of the burst
      regularity is caused by a separate effect of tachykinins, because unlike the
      burst frequency modulation it does not require the modulation of NMDA receptors
      for its induction and is blocked by H8, an inhibitor of cAMP- and cGMP-dependent
      protein kinases. The effects of substance P were mimicked by the dopamine D2
      receptor antagonist eticlopride. The effects of eticlopride were blocked by the
      tachykinin antagonist spantide II, suggesting that eticlopride may endogenously
      release tachykinins. Because locomotor activity in vitro corresponds to that
      during swimming in intact animals, we suggest that endogenously released
      tachykinins will result in prolonged modulation of locomotor behavior.

PMID- 9614254
TI  - Global surveillance for antituberculosis-drug resistance, 1994-1997. World Health
      Organization-International Union against Tuberculosis and Lung Disease Working
      Group on Anti-Tuberculosis Drug Resistance Surveillance.
AB  - BACKGROUND: Drug-resistant tuberculosis threatens efforts to control the disease.
      This report describes the prevalence of resistance to four first-line drugs in 35
      countries participating in the World Health Organization-International Union
      against Tuberculosis and Lung Disease Global Project on Anti-Tuberculosis Drug
      Resistance Surveillance between 1994 and 1997. METHODS: The data are from cross
      sectional surveys and surveillance reports. Participating countries followed
      guidelines to ensure the use of representative samples, accurate histories of
      treatment, standardized laboratory methods, and common definitions. A network of
      reference laboratories provided quality assurance. The median number of patients
      studied in each country or region was 555 (range, 59 to 14,344). RESULTS: Among
      patients with no prior treatment, a median of 9.9 percent of Mycobacterium
      tuberculosis strains were resistant to at least one drug (range, 2 to 41
      percent); resistance to isoniazid (7.3 percent) or streptomycin (6.5 percent) was
      more common than resistance to rifampin (1.8 percent) or ethambutol (1.0
      percent). The prevalence of primary multidrug resistance was 1.4 percent (range,
      0 to 14.4 percent). Among patients with histories of treatment for one month or
      more [corrected], the prevalence of resistance to any of the four drugs was 36.0
      percent (range, 5.3 to 100 percent), and the prevalence of multidrug resistance
      was 13 percent (range, 0 to 54 percent). The overall prevalences were 12.6
      percent for resistance to any of the four drugs [corrected] (range, 2.3 to 42.4
      percent) and 2.2 percent for multidrug resistance (range, 0 to 22.1 percent).
      Particularly high prevalences of multidrug resistance were found in the former
      Soviet Union, Asia, the Dominican Republic, and Argentina. CONCLUSIONS:
      Resistance to antituberculosis drugs was found in all 35 countries and regions
      surveyed, suggesting that it is a global problem.

PMID- 9614255
TI  - Association between multiple cardiovascular risk factors and atherosclerosis in
      children and young adults. The Bogalusa Heart Study.
AB  - BACKGROUND: In adults, cardiovascular risk factors reinforce each other in their
      effect on cardiovascular events. However, information is scant on the relation of
      multiple risk factors to the extent of asymptomatic atherosclerosis in young
      people. METHODS: We performed autopsies on 204 young persons 2 to 39 years of
      age, who had died from various causes, principally trauma. Data on antemortem
      risk factors were available for 93 of these persons, who were the focus of this
      study. We correlated risk factors with the extent of atherosclerosis in the aorta
      and coronary arteries. RESULTS: The extent of fatty streaks and fibrous plaques
      in the aorta and coronary arteries increased with age. The association between
      fatty streaks and fibrous plaques was much stronger in the coronary arteries
      (r=0.60, P<0.001) than in the aorta (r=0.23, P=0.03). Among the cardiovascular
      risk factors, body-mass index, systolic and diastolic blood pressure, and serum
      concentrations of total cholesterol, triglycerides, low-density lipoprotein
      cholesterol, and high-density lipoprotein cholesterol, as a group, were strongly
      associated with the extent of lesions in the aorta and coronary arteries
      (canonical correlation [a measure of the association between groups of
      variables]: r=0.70; P<0.001). In addition, cigarette smoking increased the
      percentage of the intimal surface involved with fibrous plaques in the aorta
      (1.22 percent in smokers vs. 0.12 percent in nonsmokers, P=0.02) and fatty
      streaks in the coronary vessels (8.27 percent vs. 2.89 percent, P=0.04). The
      effect of multiple risk factors on the extent of atherosclerosis was quite
      evident. Subjects with 0, 1, 2, and 3 or 4 risk factors had, respectively, 19.1
      percent, 30.3 percent, 37.9 percent, and 35.0 percent of the intimal surface
      covered with fatty streaks in the aorta (P for trend=0.01). The comparable
      figures for the coronary arteries were 1.3 percent, 2.5 percent, 7.9 percent, and
      11.0 percent, respectively, for fatty streaks (P for trend=0.01) and 0.6 percent,
      0.7 percent, 2.4 percent, and 7.2 percent for collagenous fibrous plaques (P for
      trend=0.003). CONCLUSIONS: These findings indicate that as the number of
      cardiovascular risk factors increases, so does the severity of asymptomatic
      coronary and aortic atherosclerosis in young people.

PMID- 9614256
TI  - Decreased epinephrine responses to hypoglycemia during sleep.
AB  - BACKGROUND: In patients with type I diabetes mellitus, hypoglycemia occurs
      commonly during sleep and is frequently asymptomatic. This raises the question of
      whether sleep is associated with reduced counterregulatory-hormone responses to
      hypoglycemia. METHODS: We studied the counterregulatory-hormone responses to
      insulin-induced hypoglycemia in eight adolescent patients with type I diabetes
      and six age-matched normal subjects when they were awake during the day, asleep
      at night, and awake at night. In each study, the plasma glucose concentration was
      stabilized for 60 minutes at approximately 100 mg per deciliter (5.6 mmol per
      liter) and then reduced to 50 mg per deciliter (2.8 mmol per liter) and
      maintained at that concentration for 40 minutes. Plasma free insulin,
      epinephrine, norepinephrine, cortisol, and growth hormone were measured
      frequently during each study. Sleep was monitored by polysomnography. RESULTS:
      The plasma glucose and free insulin concentrations were similar in both groups
      during all studies. During the studies when the subjects were asleep, no one was
      awakened during the hypoglycemic phase, but during the final 30 minutes of the
      studies when the subjects were awake both the patients with diabetes and the
      normal subjects had symptoms of hypoglycemia. In the patients with diabetes,
      plasma epinephrine responses to hypoglycemia were blunted when they were asleep
      (mean [+/-SE] peak plasma epinephrine concentration, 70+/-14 pg per milliliter
      [382+/-76 pmol per liter]; P=0.3 for the comparison with base line), as compared
      with when they were awake during the day or night (238+/-39 pg per milliliter
      [1299+/-213 pmol per liter] P=0.004 for the comparison with base line, and 296+/
      60 pg per milliliter [1616+/-327 pmol per liter], P=0.004, respectively). The
      patients' plasma norepinephrine responses were also reduced during sleep, whereas
      their plasma cortisol concentrations did not increase and their plasma growth
      hormone concentrations increased slightly. The patterns of counterregulatory
      hormone responses in the normal subjects were similar. CONCLUSIONS: Sleep impairs
      counterregulatory-hormone responses to hypoglycemia in patients with diabetes and
      normal subjects.

PMID- 9614257
TI  - Augmented post-induction therapy for children with high-risk acute lymphoblastic
      leukemia and a slow response to initial therapy.
AB  - BACKGROUND: Children with high-risk acute lymphoblastic leukemia (ALL) who have a
      slow response to initial chemotherapy (more than 25 percent blasts in the bone
      marrow on day 7) have a poor outcome despite intensive therapy. We conducted a
      randomized trial in which such patients were treated with either an augmented
      intensive regimen of post-induction chemotherapy or a standard regimen of
      intensive post-induction chemotherapy. METHODS: Between January 1991 and June
      1995, 311 children with newly diagnosed ALL who were either 1 to 9 years of age
      with white-cell counts of at least 50,000 per cubic millimeter or 10 years of age
      or older, had a slow response to initial therapy, and entered remission at the
      end of induction chemotherapy were randomly assigned to receive standard therapy
      (156 children) or augmented therapy (155). Those with lymphomatous features were
      excluded. Event-free survival and overall survival were assessed from the end of
      induction treatment. RESULTS: The outcome at five years was significantly better
      in the augmented-therapy group than in the standard-therapy group (Kaplan-Meier
      estimate of event-free survival [+/-SD]: 75.0+/-3.8 vs. 55.0+/-4.5 percent,
      P<0.001; overall survival: 78.4+/-3.7 vs. 66.7+/-4.2 percent, P=0.02). The
      difference between treatments was most pronounced among patients one to nine
      years of age, all of whom had white-cell counts of at least 50,000 per cubic
      millimeter (P<0.001). Risk factors for an adverse event in the entire cohort
      included a white-cell count of 200,000 per cubic millimeter or higher (P=0.004),
      race other than black or white (P<0.001), and the presence of a t(9;22)
      translocation (P=0.007). The toxic effects of augmented therapy were considerable
      but manageable. CONCLUSIONS: Augmented post-induction chemotherapy results in an
      excellent outcome for most patients with high-risk ALL and a slow response to
      initial therapy.

PMID- 9614259
TI  - Images in clinical medicine. Vertebral tuberculosis.

PMID- 9614258
TI  - Delayed cerebellar disease and death after accidental exposure to
      dimethylmercury.

PMID- 9614260
TI  - Sex differences in the use of health care services.
AB  - BACKGROUND: Sex differences in the use of health care services can be substantial
      at several stages of life. However, the extent to which differences in
      reproductive biology and mortality affect the use of health care services is
      unclear. METHODS: We studied age- and sex-specific per capita use of health care
      resources for a one-year period during 1994 and 1995 in the Canadian province of
      Manitoba, where there is universal insurance for a comprehensive range of health
      care services. Using information obtained from administrative records of
      physicians' services and acute hospital care, we tabulated the use of health care
      resources by male and female subjects in three categories: care for conditions
      specific to sex, care provided to persons who died during the study year, and
      care provided for all other conditions. RESULTS: The crude annual per capita use
      of health care resources (in Canadian dollars) was greater for female subjects
      ($1,164) than for male subjects ($918). Approximately 22 percent of health care
      expenditures for female subjects was associated with conditions specific to sex,
      including pregnancy and childbirth, as compared with 3 percent of expenditures
      for male subjects. An estimated 14 percent of health care expenditures for male
      subjects was consumed by persons who died during the study period, as compared
      with 10 percent of expenditures for female subjects. After adjustment for the use
      of health care associated with sex-specific conditions and differences in
      mortality, the female:male ratio in health care expenditures was reduced from 1.3
      to 1.0. CONCLUSIONS: Expenditures for health care are similar for male and female
      subjects after differences in reproductive biology and higher age-specific
      mortality rates among men have been accounted for.

PMID- 9614261
TI  - Clinical problem-solving. Through thick and thin.

PMID- 9614262
TI  - The global threat of drug-resistant tuberculosis.

PMID- 9614263
TI  - When should heart disease prevention begin?

PMID- 9614264
TI  - A tragic reminder about organic mercury.

PMID- 9614265
TI  - The cost of being a woman.

PMID- 9614266
TI  - GeneGenerator--a flexible algorithm for gene prediction and its application to
      maize sequences.
AB  - MOTIVATION: We developed GeneGenerator because of the need for a tool to predict
      gene structure without knowing in advance how to score potential exons and
      introns in order to obtain the best results, pertinent in particular to less well
      studied organisms for which suitable training sets are small. GeneGenerator is a
      very flexible algorithm which for a given genomic sequence generates a number of
      feasible gene structures satisfying user-defined constraints. The specific
      implementation described in detail requires minimum scoring for translation start
      and donor and acceptor splice sites according to previously trained logitlinear
      models. In addition, potential exons and introns are required to exceed specified
      minimal lengths and threshold scores for coding or non-coding potential derived
      as log-likelihood ratios of appropriate Markov sequence models. RESULTS: A
      database of 46 non-redundant genomic sequences from maize is used for
      illustration. It is shown that the correct gene structures do not always maximize
      the considered target function. However, in most cases, the correct or nearly
      correct structures are found in a small set of high-scoring structures. A
      critical review of the generated structures sometimes allows the choices to be
      narrowed by considering additional variables such as predicted splice site
      strength or local optimality of splice site scores. Summary statistics for
      prediction accuracy over all 46 maize genes are derived under cross-validation
      and non-cross-validation training conditions for the Markov sequence models. The
      algorithm achieved exon sensitivity of 0.81 and specificity of 0.75 on an
      independent set of 14 novel maize genomic segments. AVAILABILITY: GeneGenerator
      runs under Borland-Pascal 7.0 using MS-DOS and C on UNIX work stations. The
      source code is available upon request. CONTACT: jkleffe@euler.grumed.fu-berlin-de

PMID- 9614267
TI  - Transcription regulatory region analysis using signal detection and fuzzy
      clustering.
AB  - MOTIVATION: Presently available programs for the recognition of potential
      transcription factor binding sites in genomic sequences generally yield a huge
      amount of output. These output lists have to be filtered to obtain biologically
      significant elements, which is highly laborious work to be done manually.
      RESULTS: We developed a strategy for systematic verification and improvement of
      the underlying profiles, and for their contextual analysis by a fuzzy clustering
      approach using non-redundant libraries of search profiles as a prerequisite.
      AVAILABILITY: The tools mentioned in the paper are available upon request.
      CONTACT: ewi@gbf.de

PMID- 9614268
TI  - A distributed environment for physical map construction.
AB  - MOTIVATION: With the main focus of the Human Genome Project shifting to
      sequencing, bioinformatics support for constructing large-scale genomic maps of
      other organisms is still required. We attempt to provide for this with our work,
      aimed at the delivery of robust and user-friendly contig-building software on the
      WWW. RESULTS: We present a prototype distributed analytical environment for
      molecular biologists working in the area of genomic mapping. It consists of the
      WWW server for constructing contigs from users' data with a hypertext output
      connected to Java-based map visualization software. AVAILABILITY: Freely
      available on http://www.mpimg-berlin-dahlem.mpg. de/ approximately andy/server/
      CONTACT: andy@rag3.rz-berlin.mpg.de

PMID- 9614269
TI  - A genetic algorithm for designing gene family-specific oligonucleotide sets used
      for hybridization: the G protein-coupled receptor protein superfamily.
AB  - MOTIVATION: Massive oligonucleotide hybridization is one of the most promising
      technologies of functional genome analysis. The critical point is to design
      appropriate sets of oligonucleotides that can be used effectively in
      identification by hybridization. RESULTS: Using a genetic algorithm approach, we
      have attempted to design sets of oligo probes capable of identifying new genes
      belonging to a defined gene family within a cDNA or genomic library. It is not
      limited by oligonucleotide length and admits the letter 'N' in the structure of
      the oligonucleotides selected. One of the major advantages of this approach is
      the low homology required to identify functional families of sequences with
      little homology. We have designed the oligonucleotide sets that are most
      selective for the cDNA clones of transmembrane G protein-coupled receptors
      (GPCRs), a large family of proteins that form part of a modular system of
      extracellular signal transduction to the intracellular second messenger pathways.
      The accuracy of identification has been checked on the EST library containing 713
      870 cDNA sequences. A set of 15 oligos between 7 and 14 bases in length has
      correctly identified 70% of the GPCR cDNA collection sequences with 0.02% false
      positives. AVAILABILITY: The developed software is available by
      ftp://ftp.bionet.nsc. ru/pub/biology/ and on the Web page http://www.bionet.nsc.
      ru/SRCG/Oligoselector/. CONTACT: kel@.bionet.nsc.ru; sebastian. meier-ewert@gpc
      ag.com

PMID- 9614270
TI  - Systematic genomic screening and analysis of mRNA in untranslated regions and
      mRNA precursors: combining experimental and computational approaches.
AB  - MOTIVATION: The untranslated regions (UTRs) of mRNA upstream (5'UTR) and
      downstream (3'UTR) of the open reading frame, as well as the mRNA precursor,
      carry important regulatory sequences. To reveal unidentified regulatory signals,
      we combine information from experiments with computational approaches. Depending
      on available knowledge, three different strategies are employed. RESULTS:
      Searching with a consensus template, new RNAs with regulatory RNA elements can be
      identified in genomic screens. By this approach, we identify new candidate
      regulatory motifs resembling iron-responsive elements in the 5'UTRs of HemA, FepB
      and FrdB mRNA from Escherichia coli. If an RNA element is not yet defined, it may
      be analyzed by combining results from SELEX (selective enrichment of ligands by
      exponential amplification) and a search of databases from RNA or genomic
      sequences. A cleavage stimulating factor (CstF) binding element 3 of the
      polyadenylation site in the mRNA precursor serves as a test example.
      Alternatively, the regulatory RNA element may be found by studying different RNA
      foldings and their correlation with simple experimental tests. We delineate a
      novel instability element in the 3'UTR of the estrogen receptor mRNA in this way.
      AVAILABILITY: Strategy, methods and programs are available on request from
      T.Dandekar. CONTACT: dandekar@embl-heidelberg.de

PMID- 9614271
TI  - Statistics of large-scale sequence searching.
AB  - MOTIVATION: Database search programs such as FASTA, BLAST or a rigorous Smith
      Waterman algorithm produce lists of database entries, which are assumed to be
      related to the query. The computation of statistical significance of similarity
      scores is well established for single pairs of sequences and using purely random
      models. However, the multi-trial context of a database search poses new problems.
      The credibility of a certain score obtained in a database search decreases with
      the amount of data that is compared. To improve p-value computation for database
      search experiments, statistical properties of the databases, such as the
      distribution of sequence length and effects induced by frequently repeated
      sequence patterns, need to be taken into account. RESULTS: We investigated the
      SWISS-PROT protein database Release 31.0 running extensive simulations of
      database searches. A discrepancy is observed between the theoretical predictions
      and the empirical distribution. To correct for this, we evaluate the statistical
      significance of scores in the context of a database search by a contrasting semi
      random model. This model enhances purely random models by one additional
      parameter reflecting individual statistical properties of real databases. We call
      this parameter the effective size of the database. CONTACT: r.spang@dkfz
      heidelberg.de;m.vingron@dkfz-hei del berg.de

PMID- 9614272
TI  - Towards detection of orthologues in sequence databases.
AB  - MOTIVATION: Numerous homologous sequences from diverse species can be retrieved
      from databases using programs such as BLAST. However, due to multigene families,
      evolutionary relationship often cannot be easily determined and proper functional
      assignment becomes difficult. Thus, discrimination between orthologues and
      paralogues within BLAST output lists of homologous sequences becomes more and
      more important. RESULT: We therefore developed a method that attempts to
      construct a reconciled tree from a gene tree of selected sequences and its
      corresponding phylogenetic tree of the species involved (species tree). An
      interface on the Web is developed to enable users to analyse the BLAST result.
      BLAST outputs are parsed and, for the selected sequences, multiple alignments are
      constructed either globally or for local regions. Bootstrapped trees are returned
      and compared with the expected species tree. In cases of discrepancies, gene
      duplications are assumed and a reconciled tree is computed. The reconciled tree
      shows probable orthologues and paralogues as predicted.

PMID- 9614273
TI  - DIALIGN: finding local similarities by multiple sequence alignment.
AB  - MOTIVATION: DIALIGN is a new method for pairwise as well as multiple alignment of
      nucleic acid and protein sequences. While standard alignment programs rely on
      comparing single residues and imposing gap penalties, DIALIGN constructs
      alignments by comparing whole segments of the sequences. No gap penalty is
      employed. This point of view is especially adequate if sequences are not globally
      related, but share only local similarities, as is the case in genomic DNA
      sequences and in many protein families. RESULTS: Using four different data sets,
      we show that DIALIGN is able correctly to align conserved motifs in protein
      sequences. Alignments produced by DIALIGN are compared systematically to the
      results of five other alignment programs. AVAILABILITY: DIALIGN is available to
      the scientific community free of charge for non-commercial use. Executables for
      various UNIX platforms including LINUX can be downloaded at
      http://www.gsf.de/biodv/dialign.html CONTACT: werner, morgenstern@gsf.de

PMID- 9614274
TI  - New scoring schemes for protein fold recognition based on Voronoi contacts.
AB  - MOTIVATION: The genome projects produce a wealth of protein sequences.
      Theoretical methods to predict possible structures and functions are needed for
      screening purposes, large-scale comparisons and in-depth analysis to identify
      worthwhile targets for further experimental research. Sequence-structure
      alignment is a basic tool for the identification of model folds for protein
      sequences and the construction of crude structural models. Empirical contact
      potentials (potentials of mean force) are used to optimize and evaluate such
      alignments. RESULTS: We propose new scoring schemes based on a contact definition
      derived from Voronoi decompositions of the three-dimensional coordinates of
      protein structures. We demonstrate that Voronoi potentials are superior to pure
      distance-based contact potentials with respect to recognition rate and
      significance for native folds. Moreover, the scoring scheme has the potential to
      provide a reasonable balance of detail and ion such that it is also useful for
      the recognition of distantly related (both homologous and non-homologous)
      proteins. This is demonstrated here on a set of structural alignments showing
      much better correspondence of native and model scores for the Voronoi potentials
      as compared to conventional distance-based potentials. AVAILABILITY: The
      potentials are made available via the program system ToPLign (URL:
      http://cartan.gmd.de/ToPLign.html). CONTACT: Ralf.Zimmer,Ralf.Thiele@gmd.de

PMID- 9614275
TI  - Abstracts of the 29th annual meeting of the british medical ultrasound society,
      bournemouth, 9-11 december, 1997

PMID- 9614276
TI  - The value of transcranial duplex sonography in the management of patients
      subsequent to surgery for middle cerebral artery aneurysms.
AB  - OBJECTIVE: We intended to evaluate the value of transcranial color-coded duplex
      sonography (TCCS) in the management of patients after clipping of an aneurysm of
      the middle cerebral artery. Question was whether this method was able to predict
      poor clinical outcome by detection of local circulation disorders in the
      postoperative course. METHODS: A series of 15 consecutive patients was examined
      daily by TCCS. Special attention was paid to the branches of the middle cerebral
      artery distal from the clip (M2 branches). We correlated the TCCS results to the
      clinical outcome and occurrence of infarction on CCT. RESULTS: In six patients,
      one or more M2 branches could not be found in the immediate postoperative course,
      but reappeared after a period of 1-12 days in five patients. The three patients
      with a missing signal for more than 4 days suffered from infarction of the
      dependent territory and permanent neurological deficit not due to vasospasm of
      the middle cerebral artery. In the nine patients with constant TCCS signals,
      there was only one infarction due to pre-hospital systemical hypotension.
      CONCLUSION: TCCS cannot give exact postoperative information about incidental
      vessel occlusion during surgery for MCA aneurysms because M2 branches can remain
      invisible for some days without being occluded, but this invisibility seems to be
      coupled with ischemic complications.

PMID- 9614277
TI  - Peripheral intrahepatic cholangiocarcinoma: ultrasound findings and differential
      diagnosis from hepatocellular carcinoma.
AB  - OBJECTIVE: Peripheral cholangiocarcinoma may be more frequent than expected, and
      is usually asymptomatic until it is well advanced. Our purpose was to assess the
      accuracy of ultrasound in differential diagnosis. METHODS: We compared the
      sonographic findings of ten consecutive patients with histologically proven
      peripheral cholangiocarcinoma with those obtained in 26 consecutive patients with
      hepatocarcinoma detected in the same period. In every patient we performed an
      ultrasound-guided biopsy with a fine (22 gauge) cutting needle. RESULTS: In all
      patients with a final diagnosis of peripheral cholangiocarcinoma, the ultrasound
      scan disclosed multiple well-defined nodules with a hypoechoic or target pattern.
      Two patients had dilated intrahepatic bile ducts and suspected infiltration of
      the common duct. No patient had ascites. Only minimal alterations in laboratory
      examinations were found. Ultrasound-guided fine cutting needle biopsy yielded
      diagnostic material and allowed the definitive differential diagnosis.
      CONCLUSION: Peripheral cholangiocarcinoma even in Western countries may represent
      a significant proportion of all primary liver cancers. Due to non-specific
      symptomatology only intractable and far advanced cases were detected by means of
      sonography. Ultrasound findings did not differ from those found in cases of
      metastases from extrahepatic adenocarcinomas or hepatocarcinoma with multinodular
      pattern (10/26 in our series).

PMID- 9614278
TI  - The significance of colour velocity and spectral Doppler ultrasound in the
      differentiation of liver tumours.
AB  - OBJECTIVE: The aim of the work was to develop a standard protocol of colour
      velocity and spectral Doppler ultrasound (D.-US) of liver tumour vascularization
      and to estimate the value of this method in differentiation of liver tumours.
      METHODS: In 1994 and 1995, 68 patients with 128 primary and secondary liver
      tumours were observed. The final diagnosis was histologically verified. The
      diagnostic system Acuson 128 X/P 10M (Mountain View, CA) with 3.5 MHz convex
      abdominal probe was used. Qualitative features (vessel presence, vessel location
      and waveform of tumour vessel blood flow) and quantitative features (vessel
      quantity per cm2, vessel diameter, maximum velocity (Vmax), and resistance index
      (RI) of tumour artery, and Vmax of tumour portal vein) were included in the D.-US
      protocol. The differences in these features among various liver tumours were
      retrospectively analysed. RESULTS: The tumour vascularization was found more
      frequently in hepatocellular carcinoma (HCC) than in cavernous hemagioma (CavHA)
      or metastatic liver lesion (MLL) (P<0. 01). Among the tumours with detected
      vascularization, significant differences (P<0.01) were found (1) in vessel
      presence: (a) around tumour between MLL and HCC with or without liver cirrhosis
      (LC) or CavHA; (b) in periphery of tumour between HCC,CavHA, benign tumour (BT;
      hepatocellular adenoma, focal nodular hyperplasia) and MLL; (2) in detection rate
      of arterial blood flow between HCC with or without LC and CavHA or MLL. The other
      differences were not statistically significant. CONCLUSIONS: According to our
      findings D.-US can be used for the differentiation of some liver tumours when
      using the criteria: (a) vessel presence around or in periphery of tumour, and (b)
      arterial flow pattern in tumour vessels.

PMID- 9614279
TI  - Fetal sex determination by high resolution ultrasound in early pregnancy.
AB  - OBJECTIVE: Fetal sex determination by ultrasound, and its medical and ethical
      implications, has been predominantly discussed in mid and late gestation. The
      development of high resolution ultrasound equipment has provided the possibility
      of detailed visualization of the fetus in early pregnancy. The present
      prospective study investigates the feasibility and accuracy of fetal sex
      determination by transabdominal ultrasound in early pregnancy. METHODS:
      Sonographic determination of fetal sex was attempted prospectively prior to
      genetic amniocentesis in 173 fetuses from 11 to 16 weeks of gestation. The result
      of ultrasound examination was compared with the karyotype obtained from amniotic
      fluid cells. RESULTS: Sonographic sex determination was feasible in 80.3% of
      cases, and all these determinations proved to be correct. There was no difference
      in the identification rate between male (n=87) and female (n=86) sex. Fetal sex
      determination was also feasible and correct in all four sets of twins and in the
      one set of quadruplets. CONCLUSION: Fetal sex assignment in the late first and
      early second trimester can be useful in pregnancies at risk for severe sex-linked
      diseases, in fetal disorders involving the genitalia, and in the individual
      identification of multiple fetuses. Prenatal sex assignment in early pregnancy
      implicates also far-reaching ethical problems because of the potential risk of
      sex-selected abortion.

PMID- 9614280
TI  - In utero intraventricular hemorrhage and growth discordancy in a quadruplet
      pregnancy.
AB  - With the advent of real-time ultrasonography, there have been a number of
      reported cases of in utero fetal intraventricular hemorrhage. The most frequent
      etiology for this uncommon event is iso/allo-immune thrombocytopenia; however,
      other risks have also been identified. This is the first report of an in utero
      diagnosis of intraventricular hemorrhage in a multiple gestation. Severe growth
      discordancy in this quadruplet pregnancy was an associated finding.

PMID- 9614281
TI  - Sonographic measurements of the portal vein and its intrahepatic branches in
      children.
AB  - Dilatation of the portal vein is a leading sonographic sign in portal
      hypertension. Enlargement of its intrahepatic branches is found in various liver
      diseases such as cystic fibrosis and hepatic schistosomiasis. However, body
      height dependent values for pathological portal vein diameters on ultrasound have
      been published for adults only and reference values for intrahepatic portal vein
      branches have to be established. Diameters of the portal vein and of peripheral
      portal vein branches were investigated in 130 healthy European children and
      adolescents by ultrasound. The findings correlated significantly with age and
      body height. Thus, height related diameter values should be used to define
      pathological enlargement of the portal vein and its intrahepatic branches in
      children. Our reference data may contribute to improve sonographical
      investigation of portal hypertension and periportal fibrosis.

PMID- 9614282
TI  - Feto-maternal circulation: mathematical model and comparison with Doppler
      measurements.
AB  - OBJECTIVES: Clinicians are more and more frequently studying fetal blood flow
      velocity curves recorded by Doppler ultrasound in vital organs such as the
      placenta and fetal brain to evaluate fetal well-being. We have therefore
      developed a mathematical model of the utero-placental and fetal circulations
      which could be used for teaching and for a better understanding of regulatory
      mechanisms. METHODS: The model is based on two basic elements-an arterial segment
      and a bifurcation-and we have reproduced the major arteries of the feto-maternal
      circulation combining these basic elements. The mathematical model of the system
      is based on the Navier-Stokes equations. The peripheral areas such as the brain,
      kidneys and placenta are modeled by a simple Windkessel model and the model
      computes instantaneous flow and pressure at any point in the fetal arterial tree
      and the uterine arteries. RESULTS: We have compared the computed instantaneous
      flow curves and pressure with in vivo data and our results agree with the
      findings in physiological situations and in gravidic hypertension. CONCLUSIONS:
      Our model provides new interesting insights into fetal hemodynamics such as a
      better understanding of the mismatch impedance phenomena and is a promising model
      for the study of blood redistribution mechanisms in hypoxic situations.

PMID- 9614283
TI  - Interobserver, interequipment and intersubject variability of echo-Doppler
      examination of the common carotid and vertebral arteries.
AB  - OBJECTIVE: We evaluated interobserver and interequipment variability in common
      carotid and vertebral flow measurements, using seven female members of nursing
      staff as subjects, four different ultrasound machines and three different
      radiologists as operators. METHODS: The flow of the common carotid and vertebral
      arteries in each subject was examined at 0, 10, 20 and 30 min after lying down in
      a supine position. Peak velocity, end-diastolic velocity, mean velocity, systolic
      acceleration, cross-sectional area of the vessel, flow volume/min, resistance
      index and Doppler angle were measured. RESULTS: A large proportion of the
      variance of peak velocity, cross-sectional area of the vessel and flow volume was
      patient-related. Significantly different values of end-diastolic velocity, mean
      velocity, resistance index, Doppler angle and systolic acceleration were obtained
      with different equipment. Significantly different values of systolic
      acceleration, vertebral peak velocity, common carotid artery flow and Doppler
      angle were obtained by different operators. However, part of the variability may
      be physiological due to the study protocol. CONCLUSION: The use of the same
      operator and equipment is recommended in follow-up examinations.

PMID- 9614284
TI  - Doppler studies of the vascular system.
AB  - Ultrasonic Doppler methods are routinely used to study the vascular system. Flow
      and tissue motion information can be obtained by frequency and time domain
      processing. Instruments range in complexity from simple continuous wave devices
      without imaging capability through to advanced real-time 2D colour flow scanners
      and intravascular devices. 3D display is also possible. Contrast agents can be
      used to increase the detectability of blood flow signals. The properties of the
      tissue impose an envelope on achievable ultrasonic imaging. Doppler studies can
      provide information about flow velocity profile, vessel compliance, wall shear
      rate, pressure gradient, perfusion, tumour blood flow and the presence of emboli.
      These capabilities can be integrated in an holistic picture of ultrasonic
      vascular studies.

PMID- 9614285
TI  - New developments in intravascular ultrasound imaging.
AB  - IntraVascular Ultrasound Imaging (IVUS) has already been proposed in the early
      days of diagnostic ultrasound. Today, it has come under further full attention as
      a result of minimal invasive techniques. Not only excellent intravascular two
      dimensional (2D) images are presently obtained, also three-dimensional (3D)
      reconstructed images show their diagnostic value. Based on 3D information,
      quantitative data such as plaque volume can be calculated. The procedure includes
      automatic contour detection based on image segmentation methods and greatly
      speeds up clinical evaluation. With the use of additional X-ray information, the
      true tortuous vessel geometry can be reconstructed in 3D. This allows, by
      numerical modelling techniques, to calculate endothelial shear stress values,
      which in turn may indicate sites prone to stenosis. With a decorrelation
      technique for radiofrequency (RF) echo information from sequential data in the
      same beam direction and integration method over the entire cross section, blood
      velocity can be shown colour-coded during the cardiac cycle, while even blood
      flow quantification seems to be possible. In vitro as well as in vivo experiments
      have shown the feasibility of the method. Intravascular imaging can be used to
      study the biomechanical properties of atheroma components. Local radial strain,
      used as a measure of local tissue hardness, can be estimated to identify hard or
      soft plaques independently of the echogenicity contrast between plaque and vessel
      wall.

PMID- 9614286
TI  - Diabetes: the use of color Doppler sonography for the assessment of vascular
      complications.
AB  - The use of color Doppler sonography (CDS) in the assessment of diabetic vascular
      complications is not yet well established. Among the complications of the
      disease, retinopathy, nephropathy and peripheral arteriopathy are classically due
      to a vascular attack, either a micro or a macroangiopathy. The results of CDS in
      the assessment of retinopathy and nephropathy are correlated with the degree of
      the disease and the biological findings, but the diagnostic and prognostic
      benefit of these results remains unclear compared to the conventional tests.
      Doppler sonography is more helpful in peripheral arteriopathy assessment; it may
      take the place of arteriography in the most clinical situations. The technique is
      particularly useful in case of proximal atheromatous-like arteriopathy. When the
      arteriopathy is distal, mediacalcinosis, specific to diabetes, may interfere with
      the functional test like the ankle/arm pressure index measurement.

PMID- 9614287
TI  - Detection of high intensity transient signals (HITS): how and why?
AB  - HITS (high intensity transient signals) in transcranial Doppler recordings
      reflect either microemboli, both gaseous and solid, or artefacts. Various
      frequencies in number of microembolic signals (MES) have been reported in the
      same clinical condition. A possible explanation for these discrepancies may be
      different device settings and algorithms for embolus detection. For
      reproducibility of data, we suggest that studies on MES report the following
      parameters: (1) Ultrasound device; (2) transducer type; (3) insonated artery; (4)
      insonation depth; (5) algorithms for signal intensity measurement; (6) scale
      settings; (7) detection threshold; (8) axial extension of sample volume; (9) fast
      Fourier transform (FFT) size (number of points used); (10) FFT length (time);
      (11) FFT overlap; (12) transmitted ultrasound frequency; (13) high pass filter
      settings; and (14) recording time. No current system of automatic embolus
      detection has the full sensitivity and specificity required for clinical use.
      Therefore, each of the signals detected by these devices needs to be checked and
      verified by an experienced investigator. MES will help to identify the site and
      activity of the embolizing lesion. Microembolus detection might reduce the
      observation time and the number of patients needed to perform interventional
      trials. First, however, MES needs to be validated as a meaningful prognostic
      parameter. Microemboli originating from prosthetic cardiac valves are mainly
      gaseous. Therefore, they cannot serve as an indicator of the valves
      thromboembolic activity or the patient's stroke risk.

PMID- 9614288
TI  - Acute middle cerebral artery stroke and transcranial Doppler sonography.
AB  - Five studies (Zanette et al., Stroke 1995;26:430-3; Pulci et al., JEMU
      1991;12:190-5; Kuschner et al., Neurology 1991;41:109-13; Camerlingo et al., Acta
      Neurol Scand 1993;88:108-11; Kenton et al., Stroke 1997;28:1601-6) have validated
      the diagnostic and the prognostic value of Transcranial Doppler Sonography (TDS)
      at the onset of middle cerebral artery (MCA) strokes, but there is no large study
      and the interest of these investigations is often ignored. This report insists on
      the TDS methodological rules. It shows its value in the detection of MCA stenoses
      or occlusions (mainly from cardiac origin) and underlines its usefulness in
      evaluating therapeutical procedures and in defining hemodynamic consequences of
      tight internal carotid artery stenoses.

PMID- 9614289
TI  - Non-invasive ultrasound detection of endothelial dysfunction.
AB  - With high resolution ultrasound we assessed endothelial function in subjects at
      risk of atherosclerosis. We used ACUSON 128XP/10 system with 7.0 MHz linear array
      transducer. Three groups of patients (pts) were studied: 12 patients with
      essential hypertension, ten patients with 2A familial hyperholesterolamia and ten
      controls without vascular risk factors. We measured the diameter of brachial
      artery at rest, during reactive hyperaemia (with increased flow causing
      endothelium-dependent dilation), and after sublingual 0.01 mg nitroglycerin
      (causing endothelium-independent dilation). Flow-mediated dilation is not
      impaired in essential hypertension (9. 4%) compared with controls (9.5%) and
      impaired in patients with familial hyperholesterolaemia (3.0%). NTG-induced
      dilation is not impaired in familial hyperholesterolaemia (16.6%) and essential
      hypertension (14.5%) compared with controls (20.5%). The effect of hypolipidaemic
      influence (probucol and plasmapheresis) was assessed in a separate study. These
      results demonstrate the capability of ultrasound in detection of endothelial
      dysfunction, and suggest that endothelial dysfunction in patients with familial
      hyperholesterolaemia is one of the risk factors for atherosclerosis. The
      parameters of endothelial function may be used as markers of hypolipidemic
      influence on patients with hyperholesterolaemia.

PMID- 9614290
TI  - Can cerebrovascular microemboli induce cognitive impairment in patients with
      prosthetic heart valves?
AB  - Doppler ultrasonography can be used to detect the presence of emboli in the
      cerebral arterial circulation. Emboli can be produced by different sources and
      can be of different nature: solid elements as thrombi, platelet aggregates or
      atheromatous material, or gaseous when they are produced during the decompression
      phase of diving or during extracorporeal circulation (ECC) procedures. A more
      recent source of emboli has been found in the mechanical prostheic heart valves
      (MHV). The emboli generated by MHV are likely of gaseous nature and are found in
      the middle cerebral artery blood flow at a variable rate, where they are detected
      by transcranial Doppler sonography. The mechanism of production of these
      microbubbles may be related to the rapid leaflet motion especially at closure
      when very high local pressure gradients appear, which may be able to provoke a
      release of the disolved blood gas. Solid element emboli constitute a major cause
      of cerebrovascular disease and particularly stroke. Conversely, gaseous emboli
      coming from ECC or MHV are considered as clinically silent. Nevertheless,
      cognitive alterations have been reported after ECC. As the MHV carriers are
      chronically submitted to embolic events, it can be assumed that cognitive
      impairments may occur also in these patients. A preliminary study was designed to
      inpatients attention and memory in patients with normally functioning MHV and
      microemboli, with biological prosthesis and in normal subjects. In the two groups
      of patients, episodic memory was significantly altered relatively to the control
      group. In the MHV carriers group, a significant decrease in working memory
      performance was observed relatively to the two other groups. These results
      confirm a long term effect of the microembolization occuring during ECC and point
      out the effect of the chronic exposition to microemboli.

PMID- 9614291
TI  - Cardiovascular echographic and Doppler parameters for the assessment of
      orthostatic intolerance.
AB  - OBJECTIVE: To quantify the hemodynamic changes associated with orthostatic
      intolerance. METHODS: The aortic flow, the cerebral and lower limb arterial flow
      and resistance, the flow redistribution between these two areas, and the femoral
      vein distension were assessed during two orthostatic tests (tilt-up and
      LBNP:lower body negative pressure) by echography and doppler. Eight subjects
      stayed 4 days in HDT (head down tilt) in order to induce orthostatic intolerance,
      and 1 month later, 4 days in confinement. Tilt and LBNP were performed pre- and
      post-HDT and confinement. RESULTS: Orthostatic intolerance was significantly more
      frequent after HDT (63%) than after confinement (25%). At rest, the stroke volume
      was significantly decreased after HDT (-16%, P<0.01) but not after confinement.
      Cardiac and cerebral hemodynamic responses to tilt-up and LBNP were similar pre-
      and post-HDT or confinement. Conversely, during both tilt and LBNP the femoral
      resistances increased less (P<0.002), and the femoral flow reduced less (P<0.001)
      after HDT than before HDT or after confinement. The cerebral to femoral flow
      ratio increased less after HDT than before (P<0.002) but remained unchanged
      before and after confinement. This ratio was significantly more disturbed on the
      tilt test non-finisher subjects. The femoral superficial vein was more distended
      during post-HDT LBNP than pre-HDT or after confinement (IP<0.01). In conclusion,
      4 days in HDT were enough to alter the lower limb arterial and venous response to
      tilt-up and LBNP and reduced the flow redistribution in favor of the brain in all
      subjects. Confinement did not alter significantly the hemodynamic response to
      orthostatic tests. CONCLUSION: The femoral resistance index, and the cerebral to
      femoral flow ratio measured by doppler during LBNP were the best predictors for
      orthostatic intolerance.

PMID- 9614292
TI  - Estimation of acoustical streaming: theoretical model, Doppler measurements and
      optical visualisation.
AB  - An approximate solution for the streaming velocity generated by flat and weakly
      focused transducers was derived by directly solving the Dirichlet boundary
      conditions for the Poisson equation, the solution of the Navier-Stokes equation
      for the axial components of the streaming velocity. The theoretical model was
      verified experimentally using a 32 MHz pulsed Doppler unit. The experimental
      acoustical fields were produced by three different 4 mm diameter flat and focused
      transducers driven by the transmitter generating the average acoustic power
      within the range from 1 microW to 6 mW. The streaming velocity was measured along
      the ultrasonic beam from 0 to 2 cm. Streaming was induced in a solution of water
      and corn starch. The experimental results showed that for a given acoustic power
      the streaming velocity was independent of the starch density in water, changed
      from 0.3 to 40 grams of starch in 1 l of distilled water. For applied acoustic
      powers, the streaming velocity changed linearly from 0.2 to 40 mm/s. Both, the
      theoretical solutions for plane and focused waves and the experimental results
      were in good agreement. The streaming velocity field was also visualised using
      the particle image velocimetry (PIV) and two different evaluation methods. The
      first based on the FFT-based cross-correlation analysis between small sections
      for each pair of images and the second employing the algorithm of searching for
      local displacements between several images.

PMID- 9614293
TI  - [History of progress in nutritional assessment].
AB  - Progress in nutritional assessment is reviewed. 1) Initial period (1930-1959):
      The first nutritional assessment procedures were surveys designed to describe the
      nutritional status of populations on a national basis. The important relationship
      between nutritional status and health was well documented and awareness among
      surgeons and physicians of the importance of nutritional assessment increasing
      during the 1950s. Enteral nutrition techniques were established and research on
      parenteral nutrition started. 2) Established period (1960-1979): With the
      development of enteral and parenteral nutrition techniques, the determination of
      the nutritional status of individual patients took on new importance. New
      concepts and methods were devised and used in developing regions of the world and
      for the assessment of the nutritional status of hospitalized patients during the
      1970s. 4) Developing period (after 1980): After 1980, investigators began to
      examine functional indices and combinations of parameters that would have
      prognostic value in order to determine the indications for clinical outcome. Many
      types of sophisticated equipment for assessing nutritional status became
      available and encouraged the development of a new concept of body composition.
      Despite the development of such new technologies, experienced clinicians were
      able to obtain a remarkable degree of agreement. Further education of all staff
      is essential in the clinical art of detecting the early and subtle changes of
      malnutrition.

PMID- 9614294
TI  - [Progress of enteral nutrition].
AB  - Intravenous hyperalimentation and enteral nutrition are the main surgical
      nutrition methods. IVH play an active role in therapeutic nutrition, although
      made rapid progress has been made in enteral nutrition, resulting in its wide
      clinical application. Branched-chain amino acids are useful in improving the
      nitrogen balance in patients who have undergone major surgical procedures or
      significant stress. Furthermore, their superiority over a mixed oral protein diet
      in patients with hepatic encephalopathy has been confirmed clinically. Medium
      chain triglycerides (MCT) are an important energy source. Their advantages
      include easy absorbtion by the intestinal mucosa, lack of stimulation of insulin
      excretion, and suppression of the reticuloendothelial system. However, the ratio
      of long-chain triglyceride (LCT) to MCT should be evaluated in many cases. EPA
      can prevent various adult diseases. Many nutrients contain EPA and it is
      clinically used both enterally and parenterally. Glutamine is effective in the
      repair of small intestinal mucosal damage, since it suppresses bacterial
      translocation, effects of growth hormone, epidermal growth factor (EGF), and
      nucleic acid on nutritional status are being evaluated clinically. Home enteral
      nutrition (HEN) has become more common in the past five years although close,
      cooperation between medical staff and the family is necessary its success.

PMID- 9614295
TI  - [Clinical significance and problems in parenteral nutritional care].
AB  - The clinical indications for and types of intravenous nutritional support are
      reviewed from the standpoint of their advantages and disadvantages. Total
      parenteral nutrition (TPN, also known as intravenous hyperalimentation) improves
      and maintains not only nutritional status but immunocompetence in patients with
      restricted food intake, because almost all essential nutritional substrates can
      be administered in the parenteral root alone to meet energy requirements. In
      surgical fields, TPN reduces perioperative risk and complication rates and
      enhances postoperative recovery of patients with severe stress such as those
      under going thoracic esophagectomy or pancreatoduodenectomy. In addition to
      calory administration, another type of parenteral nutrition a the disease
      specific formulation has been attempted to improve directly such pathophysiologic
      conditions as renal failure, hepatic failure, or sever acute pancreatitis.
      Despite the great benefits of TPN, it is associated with several complications
      related to the indwelling catheter or to inadequate substrates administered,
      Disuse atrophy of the intestinal mucosa in patients receiving TPN to decreases
      the host defense against bacterial infection. To avoid the abuse of TPN, the
      indications for it should be selected rigorously. Moderate calory administration
      of a maximum of 15-20 cal/kg/day via a peripherally inserted catheter has been
      reevaluated in patients on short-term fasts.

PMID- 9614296
TI  - [Recent advances in the nutritional management of pediatric surgical patients].
AB  - The prognosis of pediatric surgical patients is significantly improved by
      perioperative nutritional support. However, the morbidity and mortality rates
      from intestinal failure, including short gut syndrome and allied disorders of
      Hirschsprung's disease, remain high. Recent advance in nutrition support focus on
      the management of intestinal failure. A central venous catheter is commonly used
      for long-term total parenteral nutrition (TPN) in intestinal failure, although
      the incidence of catheter-related complications is still high. A nutrition
      support team approach might reduce such complications, with the exception of deep
      vein thrombosis, which is another serious problem in intestinal failure after
      long-term TPN on which more research is needed. A other serious complication in
      long-term TPN is liver dysfunction. It is postulated that bacterial translocation
      plays an important role in TPN-associated liver damage, although so far without
      evidence. Both cyclic TPN and enteral feeding are known to be effective in
      preventing liver damage. Since we are now familiar with methods of nutritional
      support little attention is paid to complications. Therefore nutritional
      management should be reevaluated from this standpoint.

PMID- 9614297
TI  - [Adverse effects of intravenous fat emulsion administration].
AB  - Fat emulsion has been widely accepted a parenteral nutrient for the prevention of
      essential fatty acid deficiency and the supply of a high energy source. The
      following problems associated with the administration of fat emulsion are,
      however, well recognized: 1) The soy protein detected slightly in soy bean oil
      may induce allergic reactions. 2) Although administered in small quantities
      emulsified fat particles over 5 microns in diameter can cause fat emboli,
      including as pulmonary, splenic, placental, and cerebral emboli. 3)
      Hyperlipidemia may cause pulmonary hypertension and hemophagocytosis when
      triglycerides contained in the fat emulsion are intravenously administered at a
      rate greater than 0.1g/kg/hour. 4) Fat emulsion may have immunosuppressive
      effects, because emulsified fat particles phagocytized by the reticuloendothelial
      system reduce its functions. Long-chain triglyceride of the omega-6 series can
      suppress the functions of lymphocytes and neutrophils through prostaglandins. 5)
      Fungal infections, especially with Malassezia furfur which requires fat for
      growth, are sometimes associated with intravenous fat emulsion infused through a
      central venous catheter.

PMID- 9614298
TI  - [Glutamine and growth hormone for the surgical nutritional support].
AB  - Characteristic responses to surgery, trauma, and sepsis are catabolism and
      immunodepression. Nutritional therapy is important for managing patients with
      severe surgical stress. Conventional nutritional support, however, has not been
      successful in reducing morbidity and mortality rates. New nutritional support
      strategies have been aimed at enhancing protein metabolism and immunity. This
      review focuses on glutamine and growth hormone as nutritional support strategies
      for patients experiencing surgical stress. Glutamine is important in several key
      metabolic processes in critical illness. Exogenous glutamine also augments the
      functions of lymphocytes, macrophages, and neutrophils. Growth hormone has potent
      anabolic actions. Moreover, the peptides have immunostimulatory effects. These
      new modalities may be beneficial for the treatment of surgical patients.

PMID- 9614299
TI  - [Nutrition strategies for postoperative infectious complications].
AB  - A considerable amount of data suggests that postoperative infectious
      complications result from malnutrition, organ impairment, and metabolic
      disorders. Since metabolism may become deranged once a complication occurs,
      appropriate pre- and postoperative nutritional support is very important for
      preventing postoperative infections. For patients who experience postoperative
      infections such as peritonitis, pyothorax, mediastinitis, or pneumonia, a special
      feeding formula for the metabolic derangement observed in sepsis and organ
      impairment should be administered. Branched-chain amino acids (BCAAs) are
      considered to reduce protein catabolism during the course of a septic insult. A
      BCAA-enriched parenteral nutrition formula is preferable for patients who cannot
      receive enteral feeding. Enteral nutrition should always be given the first
      priority in patients with a functional intestinal tract who are unable to consume
      adequate calories orally. Enteral formulas can include special nutrients such as
      dietary fiber and glutamine-analog which exert a trophic effect on the gut mucosa
      or enhance immunocompetence.

PMID- 9614300
TI  - [Nutrition and cancer patients].
AB  - Nutritional therapy for cancer patients includes various objectives such as
      improvement of cachexia, elucidation of the mechanism of malnutrition,
      development of therapy for anorexia, nutrition support during chemotherapy or
      radiotherapy, and inhibition of tumor growth under controlled caloric intake.
      This review describes recent remarkable developments in nutritional therapy for
      cancer patients. Cytokines such as interleukin (IL)-1, IL-6, and tumor necrosis
      factor which induce proteolysis and lipolysis are involved in the cause of
      malnutrition and cachexia in cancer patients. IL-1 also plays a significant role
      in the development of cancer anorexia via direct action in the brain. For
      anorexia therapy, progestogens have been shown to improve appetite and food
      intake in cancer patients. Moreover, glutamine supplementation improves the host
      protein metabolism without enhancement of tumor growth during chemotherapy. Among
      the effects of caloric intake on anticancer therapy, AO-90, a methionine-free
      intravenous amino acid solution, has been shown to increase the antitumor effect
      of 5-fluorouracil in clinical studies. From these observations, recent progress
      in nutritional therapy for cancer patients has been remarkable. Further study of
      nutritional therapy is required in order to maintain or improve the quality of
      life of cancer patients in the future.

PMID- 9614301
TI  - [Japan Surgical Society recertification: the viewpoint of surgeons in a local
      area].
AB  - The system of recertification is evaluated from the view point of the surgeons in
      a local area. The system only requires attendance at the national meeting of the
      Japan Surgical Society and/or meetings that are designated by the Japan Surgical
      Society for recertification. Half of such meetings have been held in the Kanto
      area over the past 10 years, resulting in an imbalance in the status of
      recertification between surgeons in the Kanto area and in local areas. In
      questionnaires about surgical recertification in local areas, many respondents
      pointed out this imbalance and the necessity for changing the conditions of
      recertification. The aim of recertification must be clarified and a new system of
      recertification investigated based upon the purpose of certification without
      imbalances between areas.

PMID- 9614302
TI  - [Necrosis of the hepatocellular carcinoma nodule can aggravate metastasis].
AB  - Since the stroma of hepatocellular carcinoma is composed of sinusoid-like
      structures, cancer cells are readily released from the primary tumor with
      possible injurious consequences. A 63-year-old woman with hepatocellular
      carcinoma underwent percutaneous ethanol injection therapy. During this
      treatment, tumor thrombus developed in the right hepatic vein. Partial hepatic
      resection was performed. Six months later, multiple nodules appeared in the lung
      fields. Partial necrosis may have allowed the release of cancer cells from the
      primary tumor. Perioperative therapy should have an effect on intrahepatic
      micrometastases, because removal of the main tumor can be done surgically.

PMID- 9614303
TI  - [Gene mutation and gene diagnosis of hemophilia].

PMID- 9614304
TI  - [Molecular mechanism of cell membrane lipids].

PMID- 9614305
TI  - Urinary excretion and plasma vitamin E levels in patients with AIDS.
AB  - Individuals with acquired immunodeficiency virus (HIV) and patients with acquired
      immunodeficiency syndrome (AIDS) present a variety of pathologic alterations that
      influence their nutritional status during various stages of the disease. Previous
      studies have reported a reduction in plasma vitamin E levels in these patients
      associated with a higher production of free radicals. Individuals with infection,
      fever, or acute diarrhea excrete considerable amounts of vitamin A in urine. This
      observation raised the hypothesis that this may also be the case for vitamin E
      and that its urinary excretion may play a significant role in the reduction of
      plasma vitamin E levels. In the present investigation, 28 serologically positive
      HIV-1 (HIV group) divided into a group of 16 patients with AIDS (< 200/mm3 CD4+ T
      lymphocytes) were studied. The control group consisted of 11 healthy individuals.
      Urinary and plasma vitamin E levels were determined by high-performance liquid
      chromatography. Patients with AIDS presented reduced plasma vitamin E levels
      (15.25 +/- 12.19 mumol/L) compared with the HIV (26.40 +/- 17.01 mumol/L) and
      control (40.03 +/- 31.80 mumol/L) groups. On the other hand, urinary excretion
      was higher in the AIDS group (0.86 +/- 0.99 mumol/24 h) than in the HIV group
      (0.62 +/- 0.46 mumol/24 h) and considerably higher than in the control group
      (0.05 +/- 0.13 mumol/24 h). These results indicate elevated vitamin E excretion
      in the urine of both patients with AIDS and patients with HIV-1, levels is
      recommended for patients with HIV and patients with AIDS and, if necessary, the
      combination of existing medical therapy with vitamin supplementation to maintain
      the nutritional status related to vitamin E.

PMID- 9614306
TI  - Elimination of intraluminal colonization by antibiotic lock in silicone vascular
      catheters.
AB  - An in vitro model was designed to evaluate the efficacy of instilled
      antimicrobials to reduce or eliminate intraluminal microbial colonization.
      Minimal inhibitory concentration and minimal bactericidal concentration activity
      of appropriate test anti-infectives were determined using standard methodology
      against clinically derived and reference test strains commonly associated with
      catheter-related infection. Drug activity was validated by bioassay for the test
      anti-infectives. Reference and clinical test strains were inoculated to the
      intraluminal surface of silicone catheter segments and incubated for 30 min,
      after which the inoculum was replaced with total parenteral nutrition (TPN)
      solution and reincubated for 12 h. For 7 d, instillation of antibiotic and TPN
      solution was alternated every 12 h to simulate clinical conditions. On days 1, 4,
      and 7, catheter segments were rinsed, bisected, and sonicated for quantitative
      plate count to determine mean microbial counts per centimeter of catheter
      surface. Catheter segments were also prepared for scanning electron microscopy. A
      significant decrease in staphylococcal intraluminal colonization after
      instillation of nafcillin, ceftriaxone, gentamicin, and vancomycin was
      demonstrated (P < 0.001). Aztreonam, ceftriaxone, and gentamicin completely
      eliminated gram-negative catheter colonization (P < 0.001). Yeast was eradicated
      from the internal catheter surface after treatment with amphoteracin B, and
      fluconazole significantly decreased intraluminal colonization (P < 0.001).
      Results show a significant decrease in staphylococcal, gram-negative, and fungal
      intraluminal colonization after instillation of appropriate antimicrobial. In
      vitro results support early clinical success using this technique. Future studies
      are warranted to identify optimal drug concentrations and dosing intervals.

PMID- 9614307
TI  - Plasma glucagon-like peptide-1 (7-36) amide (GLP-1) response to liquid phase,
      solid phase, and meals of differing lipid composition.
AB  - The gut hormone glucagon-like peptide-1 (7-36) amide (GLP-1) is a potent insulin
      secretagogue. It has been proposed to be a novel treatment for non-insulin
      dependent diabetes mellitus (NIDDM). Postprandial plasma GLP-1, insulin, and
      glucose responses were measured in six healthy volunteers in response to a solid
      test meal and a liquid meal of identical composition. Responses to three
      isocaloric soups of identical macronutrient and energy content containing
      differing degrees of fat saturation were also measured. The liquid form of the
      meal released significantly more GLP-1 than the solid form (measured by
      incremental area under the curve 0-180 min: 2.5 nmol.min-1.L-1 [median]; range
      1.4-3.7 versus 1.4 nmol.min-1.L-1 [median]; range 0.6-1.8) (P < 0.05) and this
      occurred earlier (15 min versus 60 min). The incremental area under the curve for
      insulin was significantly greater following the liquid meal (incremental area
      under the curve 0-180 min: 18.5 nmol.min-1.L-1 [median]; range 15.9-35.8 versus
      17.6 nmol.min-1.L-1 [median]; range 13.7-25.5) (P < 0.05). The glucose response
      to each meal was not different. The type of fat in the soups produced no
      significant difference in GLP-1, insulin, or glucose levels. Our findings suggest
      that the physical form of a meal significantly alters the GLP-1 response, whereas
      fatty acid saturation has little effect.

PMID- 9614308
TI  - Lipid turnover in alcoholics before and after an ethanol load.
AB  - Alcohol ingestion decreases plasma free fatty acids (FFAs) and lipid oxidation.
      This study was conducted to determine palmitate turnover in alcoholics during a
      short abstinence period and after an ethanol load and in a group of nonalcoholic
      control subjects, looking for correlations between palmitate turnover, FFA,
      acetate, and acetoacetate/beta hydroxybutyrate ratio (AKBR). Palmitate C14
      turnover was studied in five alcoholics during early abstinence and after a 0.8
      g/kg ethanol load, and in five nonalcoholic normal controls. Plasma levels of
      FFA, acetate, acetoacetate, and beta hydroxybutyrate were measured before and
      during the ethanol load. A needle hepatic biopsy was performed in alcoholics. FFA
      levels, palmitate flux, oxidation, and nonoxidative disposal were similar in
      alcoholics compared with control subjects, decreasing significantly after the
      ethanol load in both groups. AKBR and ketone bodies were similar in both groups
      in the basal period. After the alcohol infusion, AKBR decreased significantly.
      Acetoacetate levels did not change, and beta hydroxybutyrate and total ketone
      bodies increased significantly in alcoholics and control subjects. A positive
      correlation was found between FFA levels and palmitate flux. Liver biopsies
      showed mild changes in the patients studied. The similar inhibition of lipid
      turnover, FFA release, and the drop in AKBR observed after an alcohol load in
      alcoholics and control subjects suggest that this effect is mediated by alcohol
      metabolism and not by metabolic alterations present in alcoholics.

PMID- 9614309
TI  - Non-protein energy overloading induces bacterial translocation during total
      parenteral nutrition in newborn rabbits.
AB  - The effect of energy intake provided by total parenteral nutrition (TPN) on the
      incidence of bacterial translocation and the relationship between TPN-induced
      cholestasis and bacterial translocation were investigated in newborn animals.
      Forty-six Japanese white newborn rabbits were divided into three groups: TPN-H
      group (high energy TPN; 280 kcal.kg-1.d-1), TPN-L group (low energy TPN; 180
      kcal.kg-1.d-1), and a control group (breast fed). On day 8, they were all killed
      for investigation of the presence of bacterial translocation, for blood chemistry
      analysis, and for histological examination of the ileum. The incidence of
      translocation to any of mesenteric lymph nodes and liver and spleen was
      significantly higher in the TPN-H group (67%) than in both the TPN-L group (13%)
      and the control group (10%) (P < 0.01). No difference was seen in ileum
      morphology between the two TPN groups. Although the mean bilirubin level of the
      TPN-H group tended to be higher than the TPN-L group, whether or not bacterial
      translocation occurred was not found to be closely related to the degree of TPN
      associated cholestasis. In conclusion, parenteral nonprotein energy overloadng
      increased the incidence of bacterial translocation in the newborn rabbit.
      However, bacterial translocation did not appear to be associated with the
      development of TPN-associated cholestasis.

PMID- 9614310
TI  - Pulmonary lipid peroxidation and antioxidant defenses during exhaustive physical
      exercise: the role of vitamin E and selenium.
AB  - Physical exercise is known to induce oxidative stress leading to the generation
      of free radicals. This increased generation of free radicals might lead to lipid
      peroxidation and tissue damage, more so under deficient/impaired antioxidant
      states. In the present study, we report the role of vitamin E and selenium (Se)
      during exercise-induced oxidative stress in the pulmonary tissue. Vitamin E
      and/or Se deficiency in female albino rats resulted in generation of free
      radicals as revealed by electron spin resonance (ESR) spectra in the lung tissue,
      indicating the onset of oxidative stress. When these animals were subjected to a
      single bout of exhaustive exercise, there was an additional increase in the
      generation of oxy-free radicals, which might lead to tissue damage. However, no
      such signals were recorded in the lung tissue of vitamin E- and Se-supplemented
      animals, when subjected to a similar exercise program, suggesting that protection
      is offered by vitamin E and Se in combating oxidative stress.

PMID- 9614311
TI  - Cardiovascular disease prevention in eastern Europe.
AB  - During the last 30 y the region of highest premature cardiovascular mortality has
      shifted from the US and Finland to Central and Eastern Europe. Present male
      cardiovascular mortality in Latvia, Estonia, the Russian Federation, and Hungary
      has overtaken the maximum cardiovascular mortality reached in the US in the
      1960s. This epidemic is only partially explainable by the high prevalence of the
      three traditional risk factors, i.e., hypercholesterolemia, hypertension, and
      smoking. The international WHO project MONICA, Finnish/Russian/Estonian,
      Swedish/Lithuanian, and US/Russian surveys have shown that there were no
      substantial differences between Eastern Europe and democratic countries regarding
      the prevalence of traditional risk factors with the significant exception of male
      smokers. The number of female smokers and plasma lipid levels (total and HDL
      cholesterol and triacylglycerols) were even more favorable in East European. The
      intake of antioxidants from domestic and imported fruits, vegetables, vegetable
      oils, and nuts in most East European countries was substantially lower than in
      the West. The failure of economical and political systems to satisfy material and
      psychosocial population needs was probably an important factor in the
      cardiovascular disease epidemic in Eastern Europe. Antioxidant deficiencies,
      alcoholism, and psychosocial stress could become "new" cardiovascular risk
      factors in Eastern Europe. Smoking and alcoholism are definitely important risk
      factors, but additional local risk factors in Eastern Europe need to be
      identified with more specific target-prevention programs in individual Eastern
      Europe countries. This region is a prospective arena for research on additional
      lesser known cardiovascular risk factors, e.g., oxidative stress, chronic
      marginal deficiency of antioxidant vitamins (vitamin C, tocopherols, carotenoids)
      and low intake of folic acid and flavonoids.

PMID- 9614312
TI  - Pregnant women with transient gastric obstruction managed by Naso-Jejunal
      nutrition.
AB  - A pregnant woman with transient gastric obstruction was fed by enteral nutrition
      alone for 11 wk and 6 d. Her body mass index of 23.2 kg/m2 before pregnancy
      declined to 21.8 kg/m2 after delivery. Although she did not gain weight during
      enteral nutrition, fetal growth, estimated by ultrasonography, was normal, and
      she delivered a 3030-g female infant at 38 wk gestation. The blood laboratory
      data during pregnancy and the breast milk after pregnancy were also normal. The
      results suggest that factors other than maternal weight gain alone should be
      considered in the evaluation of nutritional status for the pregnant woman.

PMID- 9614313
TI  - Appropriate nutritional support in acute and complicated Crohn's disease.
AB  - Crohn's disease is frequently complicated by protein-calorie malnutrition. Four
      common clinical presentations of Crohn's disease include acute exacerbations or
      flares of disease, intestinal obstruction, fistulizing disease, and perianal
      disease. In this review, we examine the role of nutritional support in these
      clinical scenarios. Nutritional support is important for maintaining functional
      status and preventing loss of lean tissue. Determinants of lean-tissue loss
      include severity of underlying injury, baseline nutritional status, and duration
      of inadequate nutrition. One of the clinically useful measures of nutritional
      status is the nutritional risk index (NRI) defined on the basis of the serum
      albumin and weight loss. Nutritional support is important in severely
      malnourished patients (NRI < 83). Enteral nutrition is the route of choice,
      provided there are no contraindications to using the gastrointestinal tract. In
      acute exacerbations of Crohn's disease, enteral nutrition also has a role in the
      primary management of disease although it is not as effective as corticosteroids
      in inducing remission. The mechanisms are poorly understood and the most
      effective enteral formulation needs to be determined. Total parenteral nutrition
      is justified in severely malnourished Crohn's disease patients who are unable to
      tolerate enteral feeding or in whom enteral feeding is contraindicated. More
      clinical studies are needed on the assessment of malnutrition in Crohn's disease,
      the effects of nutritional management on functional status, and the timing of
      nutritional intervention.

PMID- 9614315
TI  - What's new in the role of colon as a digestive organ in patients with short bowel
      syndrome.

PMID- 9614314
TI  - Catheter-sepsis during home parenteral nutrition: use of the antibiotic-lock
      technique.

PMID- 9614316
TI  - Bran: may irritate irritable bowel.
AB  - The irritable gut is known to be hypersensitive, and it is reasonable to suspect
      that patients with the disorder might be hyperreactive to agents that stimulate
      or irritate it. This appears to be a possible explanation for the adverse effects
      of bran on hospital patients with this disorder, but we do not yet know how this
      product affects community IBS sufferers. We cannot ignore the fact that fiber and
      bran have major beneficial effects in other areas, not least in the reduction of
      colonic carcinoma. In conclusion, it is probably best to recommend that patients
      with IBS be left to judge for themselves whether bran helps or exacerbates their
      symptoms, but there is enough evidence to suggest that the current dogma of
      routinely treating all IBS sufferers with bran should be challenged. Proprietary
      sources of fiber, such as ispaghula, may be more appropriate for those IBS
      subjects (for example, constipated) for whom fiber supplementation is believed
      justified.

PMID- 9614317
TI  - The health food movement.

PMID- 9614318
TI  - Obesity and fat cell thermogenesis.

PMID- 9614319
TI  - Fluoride--essential or just beneficial.

PMID- 9614320
TI  - The role of sterols in lipid emulsions for parenteral nutrition.

PMID- 9614321
TI  - Outcomes from nutritional support in the elderly.

PMID- 9614322
TI  - M. Mori's definitive recognition of vitamin A deficiency and its cure in
      children.

PMID- 9614323
TI  - Modelling the chloroquine chemotherapy of falciparum malaria: the value of
      spacing a split dose.
AB  - We have attempted to provide a rational basis for improving the protocols for
      chemotherapy of malaria. We model the regression of parasitaemia by Plasmodium
      falciparum, its subsequent elimination from the body, or recrudescence, for
      populations of cells treated with chloroquine. Our model assumes that drug forms
      a complex with some receptor in the parasite and that parasites possessing this
      complex die at a defined rate. We take into account that chloroquine is
      eliminated exponentially from the body. We show how the parameters of the model
      can be derived from observations in the field. The model correctly predicts the
      effects of drug dose, degree of initial parasitaemia, rate of parasite
      multiplication and degree of drug resistance to chloroquine chemotherapy. The
      level of parasitaemia will reduce to a minimum at sufficiently high
      concentrations of chloroquine, but only if the parasitaemia is reduced to below
      that of 1 parasite per infected person will a cure of malaria be obtained.
      Otherwise, recrudescence will, sooner or later, occur. We show that, even for
      drug-resistant malaria, if 2 doses of chloroquine are given to a patient with an
      interval of some 10 days between them, parasites can be eliminated from the body
      without toxic levels of chloroquine being reached.

PMID- 9614324
TI  - Transmission-blocking effects of sera from malaria-exposed individuals on
      Plasmodium falciparum isolates from gametocyte carriers.
AB  - Sera from donors exposed to malaria were tested for their ability to block the
      transmission of isolates from Cameroonian Plasmodium falciparum gametocyte
      carriers. Sera were selected from amongst Cameroonian and Gambian donors who had
      positive antibody reactivity against the surface of activated gametes and against
      epitopes of Pfs 48/45 (a potential transmission-blocking vaccine candidate
      antigen). Aliquots of washed blood from gametocyte carriers were resuspended in
      test and control sera and fed to An. gambiae mosquitoes via a membrane feeder.
      Comparisons of the prevalence and intensity of infections is dissected mosquitoes
      showed variations in the ability of sera to block the transmission of the
      different isolates. Sera were identified that had little or no blocking effect on
      the transmission of isolates unless the isolate was poorly infectious. Some sera
      completely blocked the transmission of some isolates whilst having little or no
      effect on others. The observed variation in transmission-modulating activity may
      have implications for the development of a transmission-blocking vaccine.

PMID- 9614325
TI  - Host searching in Argulus foliaceus L. (Crustacea: Branchiura): the role of
      vision and selectivity.
AB  - In laboratory experiments the swimming behaviour of the ectoparasite Argulus
      foliaceus and its infection rates on juvenile perch (Perca fluviatilis) and roach
      (Rutilus rutilus) were examined. The highest infection rate and a preference for
      perch juveniles were obtained in darkness, the lowest infection rate and a lack
      of preference in the light, when aquaria with glass walls (high reflectivity)
      were used. In the light, when aquaria were lined with black plastic (low
      reflectivity) an intermediate level of infection for perch and the highest for
      roach was recorded. Under such conditions roach were significantly more heavily
      infected than perch; an attack rate 4 times greater was recorded for brighter
      (more reflective) roach juveniles than for perch. Within the aquaria with a low
      reflective interior parasites swam 4.4 times slower and were observed
      predominantly in the central area, while in the highly reflective aquaria fast
      swimming A. foliaceus were recorded mainly near the walls. The primary role of
      visual stimuli for the host search behavior of A. foliaceus in the light is
      suggested. Parasites can effectively use such stimuli only in the low reflective
      surroundings. Highly reflective glass aquarium walls produce numerous secondary
      local light sources, which cause fast, erratic parasite movements and prevent the
      efficient location of potential hosts.

PMID- 9614326
TI  - Manipulation of a mollusc by a trophically transmitted parasite: convergent
      evolution or phylogenetic inheritance?
AB  - We investigated the influence of infection by the trematode Curtuteria australis
      on the burrowing behaviour of its intermediate host, the bivalve Austrovenus
      stutchburyi. Laboratory experiments and field observations revealed that cockles,
      unable to bury completely or even partially under the sediment, have a reduced
      foot length compared with buried individuals. The ability to bury proved to be
      highly repeatable in field experiments: cockles found at the surface and
      transplanted to an experimental area did not bury themselves, and cockles found
      buried stayed buried when relocated. All metacercariae of C. australis were found
      strictly in the foot and for each of 3 samples collected in different sites,
      there was a negative and significant relationship between the relative length of
      the foot and the parasite load. A predation test conducted under natural
      conditions indicated that cockles with the stunted foot and the altered behaviour
      are significantly more susceptible to predation by aquatic birds than other
      cockles. Given that the definitive host of C. australis is an oystercatcher, we
      first discuss our results in the context of transmission strategy. Comparisons
      with other studies on more or less related trematode species parasitic in
      bivalves and evolving under similar constraints for their transmission, shed
      light on the origin of this adaptation in C. australis.

PMID- 9614327
TI  - The cement apparatus of larval and adult Pomphorhynchus laevis (Acanthocephala:
      Palaeacanthocephala).
AB  - Light and electron microscopy were used to study the ultrastructure of the cement
      apparatus, namely cement glands and cement ducts of mature specimens of the
      acanthocephalan parasite Pomphorhynchus laevis Muller, 1776, recovered from the
      digestive tracts of fish Leuciscus cephalus Risso, 1826. In addition, the cement
      glands of immature P. laevis found within the body cavity of the fish Alburnus
      alburnus alborella De Filippi, 1844 were examined. In a mature male of P. laevis
      the 6 cement glands are rounded to oval in shape and each of them has an outer
      cytoplasmic layer containing nuclei and surrounding a space for storage of the
      cement material within the gland. The nuclei have an irregular outline and the
      cytoplasm of the cells contains round, membrane-bound secretory granules
      approximately 1 micron in diameter. Nuclei surrounded by secretory granules were
      present inside the gland lumen. Within the gland ducts of mature males, granules
      were present within the wall thickness and, inside the luminal area, mitochondria
      were encountered. In contrast, within the cement glands of immature P. laevis
      there were no secretory granules and the chromatin of the nuclei appeared
      condensed. The nature of the secretory product of the cement glands was
      investigated with histological and electrophoretic methods. A protein with
      molecular weight of 23 kDa was recorded as a major component of cement.

PMID- 9614328
TI  - Dietary protein and zinc restrictions independently modify a Heligmosomoides
      polygyrus (Nematoda) infection in mice.
AB  - The effects of dietary protein and zinc restrictions on Heligmosomoides polygyrus
      were compared following primary and challenge infection in female BALB/c mice fed
      either control (24%), marginal (7%) or low (3%) protein combined with either high
      or low zinc (60 or 3 mg Zn/kg diet). Dietary protein restriction (3%) resulted in
      significantly lower body weight gain. As well, blood urea nitrogen (BUN)
      significantly decreased with decreasing dietary protein level. However, neither
      plasma albumin concentration nor relative thymus or spleen weights were reduced.
      Marginal zinc deficiency was confirmed by significantly lower tibia and liver
      zinc concentration, but food intake, body weight gain, relative thymus and spleen
      weights, and alkaline phosphatase activity were not altered. On day 29 post
      primary infection, worm burdens were significantly higher in mice fed either
      marginal or low protein and in mice fed a low zinc diet, while parasite egg
      output was significantly higher in mice fed both low protein and low zinc diet.
      Immune status was compromised in mice fed low protein (significantly lower serum
      IgG1 and lower eosinophilia), and in mice fed low zinc diet (significantly lower
      eosinophilia). Early in the infection, IgE titres were elevated in mice fed low
      protein or low zinc, but IgE titres declined to levels lower that the control
      diet groups after 14-21 days. On day 29 post-challenge infection, worm burdens
      and parasite egg output were significantly higher in mice fed low protein,
      whereas the other group had expelled almost all parasites. Dietary restriction
      had no effect on IgE. Significantly reduced serum IgG1 titres and eosinophilia in
      mice fed 3% protein supported the view that low dietary protein but not low zinc
      increased host susceptibility to H. polygyrus by compromising host immune
      function following reinfection in immunized mice.

PMID- 9614329
TI  - Time-course of antibody response in mice against oral infection with eggs of
      Echinococcus multilocularis.
AB  - The kinetics of serum antibody response against infection with Echinococcus
      multilocularis eggs was evaluated in AKR mice. The animals were infected by oral
      inoculation with 300 parasite eggs, and necropsied at 1, 2, 4, 6, 9, 12 and 16
      weeks post-infection (p.i.), respectively. The parasite formed the laminated
      layer at 4 weeks p.i., the brood capsule with a massive proliferation of germinal
      cells at 9 weeks p.i. and protoscoleces at 16 weeks p.i. Serum antibody responses
      of the mice to antigen preparations from metacestodes of different stages and
      protoscoleces were evaluated by ELISA, immunoblotting and immunohistochemistry.
      In ELISA, the antibody responses began to increase at 4 weeks and became more
      apparent at 9 weeks p.i. and thereafter. Immunoblots using sera collected at 16
      weeks p.i. showed some common bands among the 3 different antigen preparations.
      In addition to this, the germinal cells and brood capsules of mature metacestodes
      were stained strongly in an immunohistochemical study. From above, it is
      suggested that some antigen molecules are expressed in the parasite through these
      stages and stimulated host antibody responses.

PMID- 9614330
TI  - Neurophysiology of glutamatergic signalling and anthelmintic action in Ascaris
      suum: pharmacological evidence for a kainate receptor.
AB  - Electrophysiological and pharmacological techniques were used to study
      glutamatergic signalling in the parasitic nematode, Ascaris suum. Glutamate or
      kainate injections into whole worms produced a paralysed quasi-static posture
      similar to the waveform in behaving worms. The DE2 motorneuron class is a primary
      target. Several glutamatergic substances produced pronounced conductance
      increases and depolarization in DE2; domoate and kainate were the most potent
      agonists tested. Glutamate responses and spontaneous excitatory post-synaptic
      potentials in DE2 were reversibly blocked in sodium-free saline. DE2 sensitivity
      to exogenous glutamate was sustained during block of synaptic transmission
      suggesting that glutamatergic receptors are located on DE2 neurons. The glutamate
      induced response was localized to the DE2 dendrite, coincident with the synapses
      responsible for spontaneous potentials in DE2. Steady-state potentials reached
      during glutamate superfusion were similar to the reversal potentials for both the
      spontaneous post-synaptic potentials and glutamate, also suggesting that these
      potentials may be glutamatergic. Non-N-methyl-D-aspartate receptor antagonists
      partially blocked spontaneous DE2 excitatory potentials and responses elicited by
      exogenous glutamate and kainate. This glutamatergic pathway may play a role in
      nematode locomotory behaviour and account for the paralysing anthelmintic action
      of excitatory amino acid analogues like kainate and domoate.

PMID- 9614331
TI  - Action of excitatory amino acids on hypodermis and the motornervous system of
      Ascaris suum: pharmacological evidence for a glutamate transporter.
AB  - Electrophysiological and pharmacological experiments suggest the presence of an
      electrogenic glutamate transporter in the motornervous system of the parasitic
      nematode Ascaris suum. This putative transporter occurs in hypodermis (a tissue
      in some respects analogous to glia) and in DE2 motorneurons, a dorsal excitatory
      motorneuron class which receives excitatory glutamatergic post-synaptic
      potentials. Glutamate application to hypodermis produced non-conductance mediated
      depolarizations that were smaller in amplitude and slower in rate of rise than
      DE2 responses where a glutamate-activated conductance occurs. The hypodermal
      response is sodium dependent and calcium independent. Excitatory amino acid
      ionotropic receptor agonists (kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionic acid and N-methyl-D-aspartate) were ineffective in eliciting hypodermal
      responses. The ionotropic receptor antagonist, 6,7-dinitroquinoline-2,3-dione,
      had no effect on hypodermal glutamate responses. The L- and D-form of glutamate,
      aspartate and homocysteate produced hypodermal and DE2 depolarizations consistent
      with the pharmacological profile for glutamate transporters in other systems.
      Glutamate transport inhibitors (L-trans-pyrrolidine-2,4-dicarboxylate and beta
      hydroxyaspartate) elicited electrogenic depolarizations in hypodermis and DE2.
      These results suggest that the hypodermal glutamate response has an electrogenic
      transporter component, while the DE2 response has 2 components, one conductance
      mediated and the other due to an electrogenic transporter.

PMID- 9614332
TI  - [Umbilical cord blood transplantation: acceptance of umbilical cord blood
      donation by pregnant patients].
AB  - BACKGROUND/OBJECTIVE: Umbilical cord blood is an alternative source for
      allogeneic transplantation of hematopoietic stem cells from related and unrelated
      donors. It can easily be collected, cryopreserved and stored in cord blood banks
      for later use. In Switzerland, cord blood banks for related and unrelated stem
      cell transplantation are being established. The aim of the study was to evaluate
      previous knowledge of the possible medical use of cord blood and acceptance of
      cord blood banking in pregnant women. METHODS: We performed a prospective open
      study using a structured, anonymous questionnaire at the University of Basel
      Women's Hospital pregnancy outpatient clinic. After concise information on the
      use of cord blood for transplantation, questions were asked concerning previous
      knowledge of the use of placenta and cord blood in general, concerning the
      attitude to donation of cord blood for transplantation, and the respondent's
      willingness to donate cord blood of her own child. Women of different ethnic
      background were compared. RESULTS: From 300 questionnaires handed out to pregnant
      women of different ethnic background attending our outpatient clinic, 250 (83%)
      were returned, and 245 could be evaluated for final analysis. Only 40% indicated
      that they did know what usually happens to the placenta after birth. In contrast,
      the vast majority (95%) supported the idea of umbilical cord blood for banking
      and later use for stem cell transplantation. Similarly, 93% stated that they
      would agree to donate the cord blood from their own child for this purpose, while
      no statistically significant differences could be identified either between women
      with or without previous knowledge or of different ethnic background.
      CONCLUSIONS: This study shows the high acceptance of umbilical cord blood
      donation for banking and stem cell transplantation purposes in pregnant women,
      irrespective of previous knowledge. As there are no major differences between
      women of different ethnic background, a high degree of diversity of HLA-types of
      donated cord blood samples can be expected and may offset the underrepresentation
      of ethnic minorities in bone marrow donor registries.

PMID- 9614333
TI  - Arousal responses to inspiratory resistive loading during REM and non-REM sleep
      in normal men after short-term fragmentation/deprivation.
AB  - The arousal response to inspiratory resistive loading in normal men is known to
      be high during REM sleep compared to non-REM sleep. We investigated whether we
      could observe the same pattern, i.e. brisk arousal from REM sleep compared to non
      REM sleep, in normal subjects who had undergone short-term sleep
      fragmentation/deprivation prior to the investigation. The arousal response to the
      repeated application of an external inspiratory resistance of 25 cm H2O/l/s was
      determined during REM and non-REM sleep in 10 healthy men after a single night
      with 4 hours of acoustically fragmented sleep. The percentage of arousals to non
      arousals occurring within 2 minutes of the load application was significantly
      higher during REM sleep than during either of the non-REM sleep stages 2 and 3/4
      and decreased significantly from stage REM to stage 2 and from stage 2 to stage
      3/4. The mean time to arousal in REM was significantly shorter than in non-REM
      stage 3/4. The duration of sleep (comparing the results of the first with the
      second half of the sleep period time) did not modify the arousal response in
      stages 2 and 3/4. Despite short-term sleep fragmentation/deprivation the night
      before the study, the arousal response to external inspiratory resistive loading
      was brisker during REM than non-REM sleep in the healthy subjects studied. The
      responses were of the same magnitude as those induced in prior studies without
      pretest sleep disturbance. This is different from what is seen in patients with
      sleep apnea, where breathing disorders are worst during REM sleep and sleep
      fragmentation/deprivation leads to rapid deterioration of arousal responses to
      the spontaneously occurring airway occlusions.

PMID- 9614334
TI  - [Combined deficiency of thyroid stimulating hormone and growth hormone in a
      diabetic patient with Hashimoto thyroiditis].
AB  - We report the case of a 36-year-old female patient with insulin dependent
      diabetes who developed hypothyroidism of pituitary origin after giving birth. She
      had low levels of free T4 and TSH with no response to i.v. TRH. Antimicrosome
      antibodies were increased (1/25000), suggesting Hashimoto's thyroiditis. The
      other hormones were normal except for a low level of growth hormone and insulin
      growth factor 1. There were no antibodies against the pituitary. MRI of the
      pituitary was normal. We suspect a vascular origin for this partial pituitary
      deficiency.

PMID- 9614335
TI  - [Chronic back pain].
AB  - Low-back pain is a very common disease in Switzerland as elsewhere, with a
      prevalence of 65%. The pain is usually due to degeneration of the motion segment,
      but subsides spontaneously in some 95% of cases irrespective of the treatment.
      Only 5% of patients still have pain after one year; but account for over 80% of
      the costs due to low-back pain. Some patients can be helped by surgical fusion;
      however; preoperative identification of the pain source is mandatory. Since there
      is no consistent correlation between pain and the degree of degeneration of
      motion segments as seen on plain radiographs, functional radiographs, CT scan or
      MRI, other diagnostic methods such as facet blocks, discography and external
      diagnostic fixation must be used. After careful patient selection a fusion
      operation may be considered. Good results after fusion operations are reported in
      60-80% of patients. The operative techniques are described.

PMID- 9614336
TI  - EPEC delivers the goods.

PMID- 9614337
TI  - New HPV E6 binding proteins: dangerous liaisons?

PMID- 9614338
TI  - Signal transduction from the Epstein-Barr virus LMP-1 transforming protein.

PMID- 9614339
TI  - Squeezing through pores: how microorganisms get into and out of the nucleus.

PMID- 9614340
TI  - New directions in molecular techniques for pathogen identification.

PMID- 9614341
TI  - Differing susceptibilities of mice, guinea pigs and rabbits to Mycobacterium
      tuberculosis.

PMID- 9614343
TI  - Immune evasion by cytomegalovirus--survival strategies of a highly adapted
      opportunist.
AB  - Slowly replicating, species-specific and complex DNA viruses, such as
      cytomegaloviruses (CMVs), which code for > 200 antigenic proteins, should be easy
      prey to the host's immune system. Yet, CMVs are amazingly adapted opportunists
      that cope with multiple immune responses. Frequently, CMVs exploit immune
      mechanisms generated by the host. These strategies secure the persistence of CMVs
      and provide opportunities to spread to naive individuals.

PMID- 9614342
TI  - The highly efficient sex-inducing pheromone system of Volvox.
AB  - The green alga Volvox is one of the simplest multicellular organisms and is
      capable of both asexual and sexual reproduction. Sexual development is initiated
      by a glycoprotein pheromone that acts at a concentration below 10(-16) M. The
      extracellular matrix (ECM) appears to play a key role in signal amplification:
      several ECM proteins contain a domain with homology to the sex-inducing
      pheromone.

PMID- 9614344
TI  - Cell receptors for picornaviruses as determinants of cell tropism and
      pathogenesis.
AB  - Recent studies have identified at least nine distinct receptors used by the
      piconaviruses for cell entry. Does the evolution of receptor usage correlate with
      the different tropisms observed in this group of viruses, and does this influence
      pathogenesis, or is it the consequence of another selection mechanism that
      favours virus survival?

PMID- 9614345
TI  - Bacterial production of carbapenems and clavams: evolution of beta-lactam
      antibiotic pathways.
AB  - Research into two of the four classes of naturally produced beta-lactams--the
      clavams and carbapenems--has started to throw light upon their biochemical
      pathways and underlying genetics. Interesting similarities between these two
      classes, from their joint discovery to an apparently common beta-lactam ring
      forming enzyme, are now being revealed.

PMID- 9614346
TI  - Multicellular spheroids: a three-dimensional in vitro culture system to study
      tumour biology.
AB  - The growth of tumour cells as three-dimensional multicellular spheroids in vitro
      has led to important insights in tumour biology, since properties of the in vivo
      tumour such as proliferation or nutrient gradients, can be studied under
      controlled conditions. While this review starts with an update of recent data on
      spheroid monocultures, especially concerning tumour microenvironment and
      therapeutic modalities, the main emphasis is put on the spectrum of heterologous
      cultures which have evolved in previous years. This type of culture includes
      tumour cell interaction with endothelial, fibroblast or immunocompetent cells.
      The relation of the spheroid culture model to other types of three-dimensional
      culture and our critical evaluation and presentation of the technical aspects of
      growing and analysing spheroids are included in the text. These topics are chosen
      to help the experimental pathologist design experiments with tumour spheroids and
      to stimulate discussion.

PMID- 9614347
TI  - Alteration in immunoexpression of glucose transporter 2 in liver of tumour
      bearing rats.
AB  - To elucidate interactions between the glucose transport system and hepatic
      glucose production in the tumour-bearing state, glycogen storage, expression of
      glucose transporter isoform 2 (Glut 2) and activities of glucose-6-phosphatase (G
      6-Pase) and hexokinase were histochemically examined in hepatocytes of tumour
      bearing rats. Five male F344 rats, subcutaneously inoculated with
      methylcholanthrene (MCA)-induced sarcoma cells were compared with five pair-fed
      animals and four ad libitum fed controls. Glycogen storage was markedly decreased
      in liver cells of tumour-bearing rats compared to in those of control animals.
      Glut 2 immunoreactivity was uniformly seen in the cellular membrane of
      hepatocytes from control animals. In rats bearing sarcoma, the staining intensity
      was significantly decreased, suggesting that Glut 2 with its bi-directional
      transport capacity was down-regulated in the tumour-bearing state. Positive
      staining for hexokinase activity was located in the perivenous area in livers
      from control animals and was more diffusely located and more intense in livers
      from tumour-bearing animals. G-6-Pase activity, limited to the peripheral area in
      livers from controls, extended to the intermediate area and had stronger
      reactivity in livers from tumour-bearing animals. In the tumour-bearing cachectic
      condition, glucose may be partially consumed by a futile cycle, hepatic metabolic
      zonation was disturbed, and the release of glucose from the liver may not be
      mediated by a facilitative glucose transporter-2.

PMID- 9614348
TI  - Contrasting phenotypes of liver-infiltrating leucocytes isolated from MCMV
      infected BALB/c and C57BL/6 mice.
AB  - We characterized liver-infiltrating leucocytes (LIL) from BALB/c and C57BL/6 mice
      0-56 days after murine cytomegalovirus (MCMV) infection. Inflammation clears from
      C57BL/6 mice 4-5 weeks post infection (pi), but persists for several months in
      BALB/c mice. The LIL obtained were 60-80% Thy 1.2+ by flow cytometry. The
      percentage of CD8+ cells rose sharply in all mice 7 days pi, with little decrease
      in BALB/c mice by day 56. CD4-CD8-Thy 1.2+/TCR alpha beta + cells were more
      prevalent in LIL than lymph node cells (LNC) irrespective of MCMV infection,
      whilst infection increased the proportion of CD8+ L-selectin- LIL (but not LNC).
      LIL from both mouse strains demonstrated cytotoxic activity against YAC-1 cells,
      but only LIL from BALB/c mice proliferated spontaneously ex vivo 21 days pi, as
      measured by tritiated thymidine incorporation. BALB/c LIL produced IFN gamma and
      IgG2a 7-21 days pi, whilst IL-10 secretion was similar in both strains. Thus,
      persistent hepatitis in BALB/c mice is associated with activation and
      proliferation of intrahepatic leucocytes with some bias towards a Th1 response.

PMID- 9614349
TI  - Collagen biosynthesis by neointimal smooth muscle cells cultured from rabbit
      aortic explants 15 weeks after de-endothelialization.
AB  - Extracellular matrix (ECM) accumulation in arterial neointima, developed in
      response to de-endothelialization, is a prolonged process. In this study, we
      examined the relationship between increased collagen accumulation and synthetic
      activity of neointimal smooth muscle cells (SMCs) derived from aortic explants
      fifteen weeks after balloon catheter injury. Freshly confluent SMCs, derived
      either from normal aorta or from aortic neointima, were used in this study. The
      newly synthesized collagen was analysed by measuring [3H]-proline incorporation;
      and the mRNA expression for two major types of collagen, collagen type I and type
      III, was studied by Northern blot analysis. Our results indicated a three fold
      increase in protein (collagen) synthesis by neointimal SMCs. At the same time,
      the steady-state mRNA for procollagen I and procollagen III was elevated five and
      three times, respectively. These data indicate that persistent synthesis
      contributes to collagen accumulation in the arterial neointima and both
      transcriptional and post-transcriptional regulation take part in this process.

PMID- 9614350
TI  - Effect of anticoagulation upon nephron obstruction in experimental acute
      ischaemic renal failure. A morphological study.
AB  - Ischaemic-reperfusion injury as a model of acute renal failure (ARF) results in
      increased macromolecular permeability, tubular obstruction, and renal oedema. To
      investigate the role for coagulation in this model, anticoagulated and saline
      pretreated rats were subjected to 60 min unilateral renal artery occlusion (RAO).
      After 15 min of reflow, specimens were collected for electron and light
      microscopic examination. Morphometry was employed to study podocyte changes and
      Bowman's space dilatation as measures of increased permeability and tubular
      obstruction, respectively. After 15 min of reflow, Bowman's space increased
      significantly and the podocytes were markedly widened and flattened. Rats
      pretreated with heparin or warfarin showed less widening of Bowman's space than
      saline-treated rats, whereas no significant difference was seen regarding the
      podocyte changes. In saline-treated rats, fibrin-positive material was seen in
      the tubules but not in the urine sediments collected after 90 min of reflow,
      either due to fibrinolysis or poor urinary elimination. The results suggest that
      anticoagulation does not preclude the glomerular sieving of macromolecules, but
      seems to reduce tubular obstruction, probably by preventing conversion of
      filtered fibrinogen into fibrin.

PMID- 9614351
TI  - Recent progress in our understanding of inhibin in the prostate gland.

PMID- 9614352
TI  - Presence and possible role of vascular endothelial growth factor in thyroid cell
      growth and function.
AB  - Angiogenesis is an important component in the development of thyroid goitre.
      Vascular endothelial growth factor (VEGF) represents a family of specific
      endothelial cell mitogens involved in normal angiogenesis and in tumour
      development. The purpose of this study was to determine the distribution of VEGF
      in thyroid tissues during goitre formation, and to study the actions of VEGF on
      the regulation of thymidine incorporation and iodine uptake by thyroid follicular
      cells. Goitre was induced in adult rats by administration of methimazole together
      with a low iodine diet. Thyroid from normal or goitrous rats was removed, fixed
      and sectioned. Immunocytochemistry performed for VEGF using the avidin-biotin
      system showed that VEGF is present in normal thyroid and is located mainly in the
      vascular endothelium and interfollicular stromal tissue. After administration of
      goitrogen for 2 weeks, which caused a two- to threefold increase in thyroid
      weight, staining of VEGF was less apparent within the interfollicular stroma, but
      strongly increased throughout the thyroid follicular and endothelial cells.
      Uptake of [125I] and incorporation of [3H]thymidine by Fisher rat thyroid cells
      (FRTL-5) were measured after 72 h culture with or without TSH or VEGF, or both.
      In the absence of TSH, incubation with VEGF caused a significant reduction in
      [3H]thymidine incorporation, but did not significantly alter [125I] uptake.
      Incubation with TSH (1 mU/ml) caused a fourfold increase in [3H]thymidine
      incorporation that was diminished by co-incubation with 10 ng/ml or greater VEGF.
      Similarly, 10 ng/ml or greater VEGF significantly reduced the ability of TSH to
      increase [125I] uptake. The antagonistic effects of VEGF on TSH-stimulated
      [3H]thymidine incorporation or [125I] uptake were significantly reduced in the
      presence of an anti-VEGF antiserum. A DNA fragment representing mRNA encoding the
      VEGF receptor, flt-1, was identified in FRTL-5 cells by reverse transcription PCR
      analysis, and the abundance of this fragment was increased in FRTL-5 cells
      cultured in the medium containing TSH (1 mU/ml) or fibroblast growth factor (FGF)
      2 (25 ng/ml). These results indicated that VEGF and one of its receptors, Flt-1,
      are present in epithelial cells of the thyroid, and that VEGF could contribute to
      the regulation of development and function of thyroid epithelial cells.

PMID- 9614353
TI  - Modulation of insulin-like growth factor (IGF) and IGF binding protein
      biosynthesis by hypoxia in cultured vascular endothelial cells.
AB  - Endothelial cells (EC) are hypoxia-tolerant and their capacity to proliferate in
      low oxygen tension is essential to maintain vascular endothelium integrity. The
      present study addresses whether hypoxia alters the expression of insulin-like
      growth factor (IGF) and IGF binding protein (IGFBP) genes in bovine aortic EC
      (BAEC) and bovine pulmonary artery EC (BPAEC). EC were cultured in normoxic (21%)
      conditions and exposed to 0% oxygen for 24, 48, or 72 h; some cells were
      reoxygenated by exposure to 21% oxygen for 24 or 48 h following hypoxia. IGF-I
      peptide and mRNA levels were very low in both cell types, and decreased further
      with exposure to hypoxia. Ligand blotting showed that both cell types synthesized
      24 kDa (IGFBP-4), 30 kDa (IGFBP-5 and/or IGFBP-6), 43 kDa and 48 kDa IGFBPs
      (IGFBP-3 glycosylation variants). IGFBP-4 was the predominant IGFBP expressed by
      both cell types and did not change with exposure to hypoxia. Hypoxia caused a
      significant increase in IGFBP-3 secretion in BPAEC but not in BAEC. IGFBP-3
      stable mRNA levels in BPAEC were increased correspondingly. IGFBP-5 was expressed
      only in BAEC and decreased with exposure to hypoxia. IGFBP-6 mRNA expression was
      low and increased in both cell types with exposure to hypoxia. These results
      demonstrate that EC IGFBP baseline expression as well as its expression in
      hypoxia vary in different vascular beds and suggest that the IGFBPs may be the
      dominant paracrine regulators of proliferation of EC as well as maintenance of
      endothelium integrity during hypoxia.

PMID- 9614354
TI  - Contribution of type II phospholipase A2 to in vitro phospholipase A2 enzymatic
      activity in human term placenta.
AB  - Although phospholipase A2 (PLA2) enzymatic activities have been implicated in the
      regulation of phospholipid metabolism and eicosanoid formation in human
      gestational tissues, the role and contribution made by individual PLA2 isozymes
      has not been established. The aim of this study, therefore, was to determine the
      contribution made by Type II PLA2 to PLA2 enzymatic activity present in human
      term placenta. The experimental paradigm used to establish the contribution made
      by Type II PLA2 to total in vitro PLA2 enzymatic activity present in placental
      extracts was to remove Type II PLA2 by immunoaffinity extraction and then to
      quantify residual PLA2 enzymatic activity. Before immunoaffinity extraction, Type
      II PLA2 immunoactivity and total PLA2 enzymatic activity present in placental
      extracts averaged 28.0 +/- 10.0 ng/mg protein and 1040 +/- 367 pmol/h per mg
      protein (n = 3) respectively. After solid-phase immunoaffinity batch extraction
      of placental extracts, immunoreactive Type II PLA2 was not detectable by ELISA,
      and PLA2 enzymatic activity was decreased by 82 +/- 1% (P < 0.001). Residual
      (i.e. non-Type II) PLA2 enzymatic activity was further characterised by Western
      blot analysis and enzyme activity assay. The data obtained are consistent with a
      contribution by both cytosolic PLA2 and other secretory PLA2 isozymes (i.e. non
      Type II) to residual PLA2 enzymatic activity. The results obtained in this study
      support the conclusion that Type II PLA2 is quantitatively the primary PLA2
      isozyme that contributes to in vitro PLA2 enzymatic activity present in extracts
      of human term placenta, accounting for at least 80% of total activity. These data
      further support the involvement of this extracellularly active isozyme in the
      regulation of placental phospholipid metabolism and eicosanoid formation during
      late gestation.

PMID- 9614355
TI  - Galanin inhibits glucagon-like peptide-1 secretion through pertussis toxin
      sensitive G protein and ATP-dependent potassium channels in rat ileal L-cells.
AB  - The neuropeptide galanin is widely distributed in the gastrointestinal tract and
      exerts several inhibitory effects, especially on intestinal motility and on
      insulin release from pancreatic beta-cells. The presence of galanin fibres not
      only in the myenteric and submucosal plexus but also in the mucosa, prompted us
      to investigate the regulatory role of galanin, and its mechanism of action, on
      the secretion of the insulinotropic hormone glucagon-like peptide-1 (GLP-1). Rat
      ileal cells were dispersed through mechanical vibration followed by moderate
      exposure to hyaluronidase, DNase I and EDTA, and enriched for L-cells by
      counterflow elutriation. A 6- to 7-fold enrichment in GLP-1 cell content was
      registered after elutriation, as compared with the crude cell preparation (929 +/
      81 vs 138 +/- 14 fmol/10(6) cells). L-cells then accounted for 4-5% of the total
      cell population. Bombesin induced a time-(15-240 min) and dose- (0.1 nM-1 microM)
      dependent release of GLP-1. Glucose-dependent insulinotropic peptide (GIP, 100
      nM), forskolin (10 microM) and the phorbol ester 12-0-tetradecanoylphorbol-13
      acetate (TPA, 1 microM) each stimulated GLP-1 secretion over a 1-h incubation
      period. Galanin (0.01-100 nM) induced a dose-dependent inhibition of bombesin-
      and of GIP-stimulated GLP-1 release (mean inhibition of 90% with 100 nM galanin).
      Galanin also dose-dependently inhibited forskolin-induced GLP-1 secretion (74% of
      inhibition with 100 nM galanin), but not TPA-stimulated hormone release.
      Pretreatment of cells with 200 ng/ml pertussis toxin for 3 h, or incubation with
      the ATP-sensitive K+ channel blocker disopyramide (200 microM), prevented the
      inhibition by galanin of bombesin- and GIP-stimulated GLP-1 secretion. These
      studies indicate that intestinal secretion of GLP-1 is negatively controlled by
      galanin, that acts through receptors coupled to pertussis toxin-sensitive G
      protein and involves ATP-dependent K+ channels.

PMID- 9614356
TI  - Pre-autoimmune thyroid abnormalities in the biobreeding diabetes-prone (BB-DP)
      rat: a possible relation with the intrathyroid accumulation of dendritic cells
      and the initiation of the thyroid autoimmune response.
AB  - Thyroid autoimmune reactions start with an accumulation of mainly dendritic cells
      in the thyroid. There is increasing evidence that, apart from being antigen
      presenting cells, they are also able to control the growth and hormone synthesis
      of neighbouring endocrine cells. The questions thus arise: are dendritic cells
      accumulating in the pre-autoimmune thyroid in response to an altered
      proliferative or metabolic activity of thyrocytes, and do cytokines, monocyte
      chemoattractants, or both, have a role in their accumulation? We have
      investigated these questions in thyrocytes of the biobreeding diabetes-prone (BB
      DP) rat in relation to the start of the intrathyroid accumulation of dendritic
      cells--that is, at about 9 weeks of age. BB-DP rats and Wistar rats (controls)
      were studied from 3 to 20 weeks of age. Hyperplastic goitre development was
      studied by assessing the thyroid weight and by measuring the number of thyrocyte
      nuclei per 0.01 mm2 thyroid section. In addition, the in situ expression of
      interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), monocyte
      chemotactic protein-1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1)
      were studied by immunohistochemistry. The in vitro proliferative capacity of BB
      DP and Wistar thyrocytes was measured by tritiated-thymidine ([3H]TdR) and
      bromodeoxyuridine (BrdU) incorporation into reconstituted, TSH- and non-TSH
      stimulated, cultured thyroid follicles. Further in vitro studies consisted of
      measurement of the production of thyroxine (T4), triiodothyronine (T3),
      thyroglobulin, IL-6, TNF-alpha and MCP-1 by the thyroid follicles. BB-DP rats
      developed a small hyperplastic goitre between the ages of 9 and 12 weeks. The in
      vitro proliferative rate of thyrocytes isolated from hyperplastic BB-DP thyroids
      was significantly lower than that of Wistar thyrocytes. This phenomenon also
      occurred in follicles isolated from BB-DP rats before hyperplastic goitre
      development, which produced significantly less T4, but more T3, than did Wistar
      follicles of the same age. At the time of and after hyperplastic goitre
      development, BB-DP follicles exhibited altered metabolic behaviour and produced
      significantly more T4, but equal amounts of T3 compared with both Wistar
      follicles of the same age and follicles of younger BB-DP rats (both under basal
      conditions and TSH-stimulated). In vitro IL-6 production by these BB-DP thyroid
      follicles was also increased. There was no noteworthy difference in production of
      thyroglobulin and MCP-1 between BB-DP and Wistar follicles at any age. TNF-alpha
      was not produced by BB-DP or Wistar thyroid follicles. Immunohistochemistry
      revealed the expression of IL-6 by both BB-DP and Wistar thyroid follicle cells
      at all times of sampling. MCP-1 and TNF-alpha were expressed only when
      infiltrates were present in BB-DP thyroids (restricted to leucocytes, ages > 18
      weeks). Modest ICAM-1 expression was restricted to large blood vessels in both BB
      DP and Wistar thyroids; in the case of infiltrates (BB-DP rat) alone, high ICAM-1
      expression was found on blood vessels and leucocytes in these infiltrations. At
      the time of intrathyroidal dendritic cells accumulation, BB-DP rats develop a
      small hyperplastic goitre. At that time there is also in vitro evidence for a
      shift to a higher production of thyroxine and IL-6 from thyrocyte follicles. The
      in vitro proliferation rate of BB-DP thyrocytes is, however, abnormally low (both
      in the pre- and hyperplastic period). Similar pre-autoimmune thyroid growth
      abnormalities have been described in another animal model of thyroid autoimmune
      disease, the obese strain chicken.

PMID- 9614357
TI  - Stimulatory effect of insulin-like growth factor I on proliferation of mouse
      pituitary cells in serum-free culture.
AB  - IGF-I is synthesized in the human and rat anterior pituitary glands. The present
      study was designed to clarify the growth-promoting action of IGF-I on mouse
      pituitary cells in a primary serum-free culture system. Proliferation of
      pituitary cells was detected by monitoring the cellular uptake of
      bromodeoxyuridine (BrdU). BrdU labelling in the nucleus was found in all types of
      secretory cells: corticotrophs, thyrotrophs, gonadotrophs (LH cells and FSH
      cells), somatotrophs and mammotrophs. IGF-I (75 ng/ml) stimulated the
      proliferation of corticotrophs and mammotrophs among the pituitary secretory
      cells. IGF-I receptor mRNA was detected in the cultured pituitary cells using
      reverse transcription (RT)-PCR, indicating that mouse pituitary cells expressed
      IGF-I receptors. Insulin (100 ng/ml) or IGF-I (7.5 ng/ml) failed to increase the
      percentage of BrdU-labelled cells. However, treatment with insulin (100 ng/ml)
      plus IGF-I (7.5 ng/ml) increased the percentage of BrdU-labelled cells in a
      synergistic-like manner. Genistein, a tyrosine kinase specific inhibitor,
      decreased the IGF-I-induced cell proliferation, indicating that IGF-I acts
      through IGF-I receptors. IGF-I mRNA was also detected in the cultured pituitary
      cells by RT-PCR, and its peptides were immunocytochemically detected. The present
      results demonstrate that all types of pituitary secretory cells have the ability
      to proliferate in our serum-free culture system. IGF-I synthesized in the
      pituitary gland may stimulate the growth of pituitary cells, in particular
      corticotrophs and mammotrophs, by an autocrine or paracrine mechanism.

PMID- 9614358
TI  - beta-Naphthoflavone abolishes interrenal sensitivity to ACTH stimulation in
      rainbow trout.
AB  - We report for the first time that beta-naphthoflavone (BNF) abolishes ACTH
      stimulation of cortisol production in rainbow trout (Oncorhynchus mykiss). There
      was significantly higher hepatic cytochrome P450 content and ethoxyresorufin O-de
      ethylase and uridine-5'-diphosphoglucuronic acid transferase activities in BNF
      treated fish than in sham-treated controls. BNF did not significantly affect
      either plasma turnover or tissue distribution of [3H]cortisol-derived
      radioactivity. Hepatic membrane fluidity and hepatocyte capacity for cortisol
      uptake were not altered by BNF as compared with the sham-treated fish. These
      results taken together suggest that BNF does not affect cortisol-clearance
      mechanisms in trout. A 3 min handling disturbance period elicited a plasma
      cortisol response in the sham-treated fish; however, the response in the BNF
      treated fish was muted and significantly lower than in the sham fish. This in
      vivo response corroborates the lack of interrenal sensitivity to ACTH in vitro in
      the BNF-treated fish, suggesting that BNF affects the ACTH pathway in trout. Our
      results suggest the possibility that cytochrome P450-inducing compounds may
      affect cortisol dynamics by decreasing interrenal responsiveness to ACTH
      stimulation in fish, thereby impairing the physiological responses that are
      necessary for the animal to cope with the stressor.

PMID- 9614359
TI  - Changes in progesterone receptor mRNA content in the rabbit lung during early
      pregnancy and after sex steroid hormone treatment.
AB  - In this work we determined progesterone receptor (PR) mRNA content in female
      rabbit lung during the first 5 days of pregnancy and in ovariectomized animals
      after subcutaneous injection of oestradiol benzoate (25 micrograms/kg) for 2 days
      or oestradiol benzoate (25 micrograms/kg) for 2 days plus a single dose of
      progesterone (5 mg/kg) on day three. On each day (0-5) of pregnancy and 24 h
      after the last dose in the case of the treated animals, animals were killed and
      lung was excised; total RNA was extracted and processed for Northern blot
      analysis. The results showed three main PR mRNA transcripts (6.1, 4.4 and 1.8 kb)
      in rabbit lung. The 4.4 kb species was the most abundant. PR mRNA content was
      markedly increased by oestradiol benzoate and downregulated by progesterone. It
      significantly increased on the first day of pregnancy and then diminished
      progressively, reaching its lowest value on day 5. These findings suggest that PR
      mRNA content in the rabbit lung is regulated by sex steroid hormones and changes
      according to the physiological concentrations of oestradiol and progesterone.

PMID- 9614360
TI  - Serum leptin levels in hypo- and hyperthyroidism.
AB  - Leptin, the product of the ob gene, is an important circulating signal for the
      regulation of body weight. In the present study the role of immunoreactive leptin
      (leptin-IR) was investigated in functional thyroid disease. Serum leptin-IR
      levels of 23 hypothyroid and 19 hyperthyroid patients were compared with 21
      controls. Leptin-IR was quantified by a specific RIA. In hyperthyroid patients,
      leptin-IR was not different from controls. Serum leptin-IR levels were
      significantly increased in hypothyroid patients (21.0 +/- 2.7 micrograms/l vs
      controls 10.8 +/- 2.1 micrograms/l, P = 0.0044). When serum leptin of hypothyroid
      patients was compared with euthyroid controls of the same body mass index the
      difference was still significant (P = 0.0333 by paired Student's t-test). This
      might indicate that elevation of the serum leptin level does not merely reflect
      changes in body weight secondary to hypothyroidism, but might be increased to
      overcome the gain of body weight caused by hypothyroidism.

PMID- 9614361
TI  - The effects of recombinant human IGF-I administration on concentrations of acid
      labile subunit, IGF binding protein-3, IGF-I, IGF-II and proteolysis of IGF
      binding protein-3 in adolescents with insulin-dependent diabetes mellitus.
AB  - The long term therapeutic potential of recombinant human (rh) IGF-I
      administration in insulin-dependent diabetes mellitus (IDDM) may be determined by
      changes in the IGF binding proteins (IGFBPs) and thus the bioavailability of IGF
      I. We have therefore studied the effects of a single subcutaneous dose of rhIGF-I
      (40 micrograms/kg at 1800 h), when compared with an untreated control night, in
      17 subjects with IDDM, on serum concentrations of IGF-I, IGF-II, IGFBP-3, acid
      labile subunit (ALS), and IGFBP-3 proteolysis. Mean (+/- S.E.M.) IGF-I levels
      increased from 242 +/- 30 ng/ml to 399 +/- 26 ng/ml (P = 0.01) after rhIGF-I
      whereas IGF-II levels declined from 600 +/- 45 ng/ml to 533 +/- 30 ng/ml. There
      was a small overnight reduction in baseline ALS levels from 48 +/- 2.8 to 44.5 +/
      3.2 micrograms/ml (P = 0.04) after rhIGF-I administration. An early fall in
      IGFBP-3 concentrations on the control night was not seen after rhIGF-I and
      overall mean levels were increased (5.2 +/- 0.2 micrograms/ml vs 4.9 +/- 0.2
      micrograms/ml, P = 0.04, on the control night). On the baseline night, IGFBP-3
      levels correlated with the sum of IGF-I and IGF-II (r = 0.73, P = 0.02) and with
      levels of the ALS (r = 0.7, P = 0.002). However after rhIGF-I, the sum of IGF-I
      and IGF-II no longer correlated with IGFBP-3, whereas the relationship with ALS
      was maintained. Immunoblot studies in six subjects indicated that 60%-70% of the
      IGFBP-3 was detected as a low molecular weight fragment at 1900 h on both study
      nights, but the amount of fragment declined to approximately 50% at 0100 h and
      45% at 0700 h. In conclusion, despite a slight but significant fall in ALS, IGFBP
      3 levels rise after rhIGF-I administration in IDDM. This cannot be explained by
      alterations in IGFBP-3 proteolysis, and may relate to the relative stability of
      ALS/IGFBP-3 when complexed principally with IGF-I rather than IGF-II.

PMID- 9614362
TI  - The anti-catabolic efficacy of insulin-like growth factor-I is enhanced by its
      early administration to rats receiving dexamethasone.
AB  - The anti-catabolic efficacy of IGF-I treatment commencing before, with or after
      the onset of catabolism was compared in order to test whether earlier treatment
      can more effectively blunt a catabolic response. Young rapidly growing male rats
      (145 g body weight) and old weight-stable female rats (270 g body weight) were
      used in two experiments. The IGF-I variant LR 3IGF-I was continuously infused at
      280 micrograms/day from 2 days before (early), concurrent with or 2 days after
      (delayed) commencement of a 6 day dexamethasone infusion (125 micrograms/kg per
      day). Both early and delayed treatment of young rats with LR 3IGF-I significantly
      reduced the measured catabolic effects of dexamethasone. Early treatment was more
      effective than delayed treatment, with significantly higher nitrogen balance (90
      +/- 12 vs 31 +/- 6 mg/day), carcass nitrogen gain (0.37 +/- 0.27 vs -1.13 +/-
      0.10% per day) and protein fractional synthesis rates after 2 (10.4 +/- 0.5 vs
      8.3 +/- 0.2% per day) and 6 days of dexamethasone (8.2 +/- 0.6 vs 7.0 +/- 0.3%
      per day). Similarly, fractional breakdown rates of carcass protein were
      maintained at significantly lower levels in rats given early treatment (6.23 +/-
      0.24 vs 6.60 +/- 0.22% per day). In contrast, the old rats were less responsive
      to LR 3IGF-I treatment and only early and concurrent treatment significantly
      reduced the catabolic response, partly because of higher food intake. Early
      treatment was superior to delayed treatment and led to significantly higher
      nitrogen balance(-19 +/- 11 vs -83 +/- 7 mg/day) and carcass nitrogen fractional
      gain (-1.19 +/- 0.40 vs -2.76 +/- 0.37% per day) as well as lower final rates of
      carcass protein fractional breakdown (3.55 +/- 0.15 vs 3.83 +/- 0.07% per day).
      These experiments show that early (prophylactic) treatment with IGF-I is superior
      to delayed treatment for reducing catabolism induced by dexamethasone. The
      results provide the basis for further research to determine if prophylactic IGF-I
      treatment is useful in other circumstances where catabolism can be anticipated,
      such as in elective major surgery.

PMID- 9614363
TI  - Specific receptors for synthetic GH secretagogues in the human brain and
      pituitary gland.
AB  - In vitro studies have been performed to demonstrate and characterize specific
      binding sites for synthetic GH secretagogues (sGHS) on membranes from pituitary
      gland and different human brain regions. A binding assay for sGHS was established
      using a peptidyl sGHS (Tyr-Ala-hexarelin) which had been radioiodinated to high
      specific activity at the Tyr residue. Specific binding sites for 125I-labelled
      Tyr-Ala-hexarelin were detected mainly in membranes isolated from pituitary gland
      and hypothalamus, but they were also present in other brain areas such as choroid
      plexus, cerebral cortex, hippocampus and medulla oblongata with no sex-related
      differences. In contrast, negligible binding was found in the thalamus, striatum,
      substantia nigra, cerebellum and corpus callosum. The binding of 125I-labelled
      Tyr-Ala-hexarelin to membrane-binding sites is a saturable and reversible
      process, depending on incubation time and pH of the buffer. Scatchard analysis of
      the binding revealed a finite number of binding sites in the hypothalamus and
      pituitary gland with a dissociation constant (Kd) of (1.5 +/- 0.3) x 10(-9) and
      (2.1 +/- 0.4) x 10(-9) mol/l respectively. Receptor activity is sensitive to
      trypsin and phospholipase C digestion, suggesting that protein and phospholipids
      are essential for the binding of 125I-labelled Tyr-Ala-hexarelin. The binding of
      125I-labelled Tyr-Ala-hexarelin to pituitary and hypothalamic membranes was
      displaced in a dose-dependent manner by different unlabelled synthetic peptidyl
      (Tyr-Ala-hexarelin, GHRP2, hexarelin, GHRP6) and non-peptidyl (MK 0677) sGHS. An
      inhibition of the specific binding was also observed when binding was performed
      in the presence of [D-Arg1-D-Phe5-D-Trp7,9-Leu11]-substance P, a substance P
      antagonist that has been found to inhibit GH release in response to sGHS. In
      contrast, no competition was observed in the presence of other neuropeptides
      (GHRH, somatostatin, galanin or Met-enkephalin) which have a known influence on
      GH release. In conclusion, the present data demonstrate that sGHS have specific
      receptors in human brain and pituitary gland and reinforce the hypothesis that
      these compounds could be the synthetic counterpart of an endogenous GH
      secretagogue involved in the neuroendocrine control of GH secretion and possibly
      in other central activities.

PMID- 9614364
TI  - Effects of acute and chronic food restriction on the insulin-like growth factor
      axis in the guinea pig.
AB  - The effect of fasting (17-18 h) versus food restriction (70% for 80 +/- 13 days)
      on the IGF-IGF binding protein (BP) axis in female guinea pigs was studied and
      related to body weight, weight gain and food conversion efficiency. Circulating
      IGF-I was reduced in the fasted (13%) and food-restricted (50%) animals. IGF-II
      was only decreased (61%) in the food-restricted group. There was no effect of
      fasting on IGFBP-1 to -4 while IGFBP-1, -3 and -4 were reduced by 56%, 60% and
      44% respectively, and IGFBP-2 increased by 72%, in the food-restricted group.
      Food restriction reduced the relative sizes of fat depots, spleen, liver, thymus
      and heart, increased those of adrenals, kidneys, pancreas, gastrointestinal
      tract, M. Biceps, M. Soleus and brain while those of uterus, lungs, thyroids and
      M. Gastrocnemius were unchanged. IGFBP-1 and -2 were negatively correlated to
      weight gain and food conversion efficiency in the ad libitum-fed group, while IGF
      I, -II, IGFBP-1, -3 and -4 were positively correlated to body weight, weight gain
      and food conversion efficiency in the food-restricted group. The results show
      that acute and chronic food restriction have different consequences for the IGF
      IGFBP axis. Furthermore, IGF-II as well as IGF-I are implicated in the control of
      body weight, weight gain and food conversion efficiency under conditions of
      restricted nutrition. Finally, IGFBP-1 and -2 may have different roles during
      chronic undernutrition compared with unrestrained nutrition in adult life.

PMID- 9614365
TI  - Effect of early luteal phase administration of mifepristone (RU486) on leukaemia
      inhibitory factor, transforming growth factor beta and vascular endothelial
      growth factor in the implantation stage endometrium of the rhesus monkey.
AB  - A single, low-dose administration of a potent antiprogesterone such as
      mifepristone (RU486) in the early luteal phase results in inhibition of
      blastocyst implantation in primates. The aim of the present study was to examine
      the status of leukaemia inhibitory factor (LIF), transforming growth factor beta
      (TGF beta) and vascular endothelial growth factor (VEGF) in day 6 gestational
      endometrium of rhesus monkeys with or without exposure to a single dose (2 mg/kg
      body weight, s.c.) of mifepristone on day 2 after ovulation. Densitometric
      analyses of immunoblots of endometrial spent media revealed an increase (P <
      0.01) in TGF beta pan (TGF beta 1, 2, 3 and 5) and a decrease (P < 0.01) in VEGF
      secretion from RU486-exposed endometrial samples compared with control samples.
      Secretory profiles for LIF, TGF beta 1 and TGF beta 1 LAP (latency associated
      peptide) remained unchanged in the two treatment groups. Morphometric analyses of
      immunohistochemical staining showed altered cell-specific distribution. TGF beta
      1 (P < 0.01) and TGF beta pan (P < 0.02) were higher, while VEGF declined (P <
      0.05) in endometrial glands of RU486-exposed endometria compared with control
      tissue samples. Stromal cell staining patterns for all experimental cytokines
      studied remained unchanged. In blood vessels, VEGF was found to be low (P <
      0.05), while LIF (P < 0.05) and TGF beta 1 (P < 0.01) were higher in mifepristone
      exposed endometrial samples compared with control tissue samples. Increased TGF
      beta secretion together with elevated levels of TGF beta in glandular epithelia
      and in blood vessels with no apparent change in stromal levels of TGF beta or in
      levels of TGF beta LAP in any endometrial compartment in the two treatment groups
      suggest an altered paracrine involvement of this cytokine and an enhanced
      activation of latent TGF beta in endometrium following mifepristone treatment.
      Higher levels of TGF beta in gland cells may result in dysregulated growth
      control and degenerative morphology. Also, higher levels of LIF and TGF beta
      together with lower levels of VEGF in the vascular compartment in mifepristone
      exposed endometrium suggest that endometrial vascular physiology is a target of
      this anti-progestin during the peri-implantation stage. It is thus plausible that
      LIF, TGF beta and VEGF in the glandular and vascular compartments of implantation
      stage endometrium play important roles in rendering the endometrium receptive,
      and that early luteal phase treatment with an anti-progestin such as mifepristone
      affects the involvement of these cytokines resulting in endometrial
      contraception.

PMID- 9614366
TI  - Stress responsiveness of the pituitary-interrenal axis during early life stages
      of common carp (Cyprinus carpio).
AB  - Whole-body levels of ACTH, alpha-MSH and cortisol in eggs and larvae of the
      common carp (Cyprinus carpio) were determined periodically up until 168 h after
      fertilisation. ACTH, alpha-MSH and cortisol immunoreactivity was detected in
      unfertilised eggs, and endogenous production of ACTH and alpha-MSH was observed
      24 h after fertilisation and that of cortisol 36 h after fertilisation. ACTH
      immunoreactivity reached peak levels before hatching (56-72 h after
      fertilisation) and remained relatively stable thereafter, while alpha-MSH
      immunoreactivity started to increase after hatching. At 36 h after fertilisation,
      whole-body cortisol levels increased rapidly reaching peak levels at the end of
      hatching (72 h after fertilisation), remaining stable until the end of the
      experiment. From 50 h after fertilisation onwards, embryos and larvae increased
      their whole-body cortisol levels when subjected to handling (mechanical pressure
      during egg stage or netting during the larval stage). It is concluded that the
      pituitary-interrenal axis in carp is fully functional at the time of hatching. No
      indications of a stress non-responsive period after hatching were observed. To
      characterise ACTH and alpha-MSH immunoreactivities in carp larvae, whole-body
      homogenates were analysed by HPLC, with pituitary homogenates of adult carp
      serving as a reference. ACTH and alpha-MSH immunoreactivity in carp larvae
      homogenates consisted of three and two products respectively. HPLC of adult carp
      pituitaries revealed the presence of two ACTH immunoreactive products, which may
      represent a phosphorylated and a non-phosphorylated ACTH variant, while the three
      alpha-MSH peaks most likely represent des-acetylated, mono-acetylated and di
      acetylated alpha-MSH, the latter being the predominant form. In carp larvae,
      however, one of the ACTH immunoreactive products co-eluted with the non
      phosphorylated ACTH, while the two alpha-MSH products identified co-eluted with
      des-acetylated and mono-acetylated alpha-MSH, indicating that POMC processing at
      this stage of development is different from prohormone processing in adult fish.

PMID- 9614367
TI  - Temporal expression and cellular localization of a gastrin-releasing peptide
      related gene in ovine uterus during the oestrous cycle and pregnancy.
AB  - Synthesis of both mRNA and peptide for gastrin-releasing peptide (GRP) has been
      demonstrated in the pregnant endometrium of sheep and women. However, it is not
      known whether GRP is synthesized in the sheep uterus during the oestrous cycle.
      Furthermore the cellular site of GRP mRNA synthesis in the uterus has not been
      determined. Therefore we examined the synthesis of GRP and determined the
      cellular location of GRP peptide and mRNA in sheep uterus taken at different
      times during the oestrous cycle (duration 17 days) and pregnancy (duration 145
      days). Northern blot analysis of RNA isolated from ovine endometrium revealed low
      or no GRP mRNA at days 4, 10, 12 and 14 of the oestrous cycle and a 24-fold rise
      in GRP mRNA (normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA)
      between days 14 and 16. A similar pattern was observed during early pregnancy,
      with a 12-fold rise in GRP mRNA:GAPDH mRNA between days 17 and 20 of pregnancy.
      Levels of GRP peptide were determined by RIA and found to be low in endometrium
      isolated at days 4, 10, 12 and 14 of the oestrous cycle (1.0-1.6 pmol/g) and 4 to
      5-fold higher at day 16. In situ hybridization localized GRP synthesis to the
      epithelial cells of the uterine glands at day 16 of the oestrous cycle and at
      days 17, 20, 40 and 50 of pregnancy. At day 140 of pregnancy diffuse
      hybridization to cells of the myometrium was also observed. Immunohistochemistry
      localized GRP peptide to the apical cytoplasm of uterine glandular epithelial
      cells at day 16 of the oestrous cycle. For samples obtained at day 20 of
      pregnancy, the area surrounding the glands also showed moderately strong
      staining. Further staining in the glandular lumen and the stromal tissue
      surrounding the glands was apparent at day 140 of pregnancy. No GRP
      immunoreactivity could be detected in the peripheral plasma during the oestrous
      cycle or the first 20 days of pregnancy. Sizing chromatography of GRP
      immunoreactivity extracted from endometrial tissue taken at day 10 of the
      oestrous cycle revealed two peaks that co-eluted with GRP(1-27) and GRP(18-27).
      However, during luteolysis and oestrus the major peak of GRP immunoreactivity
      extracted from endometrial tissue was larger than GRP(1-27) and similar to that
      seen previously in the gravid ovine endometrium. These studies demonstrate that a
      peptide similar to, but larger than, GRP is a major product of the glandular
      epithelium of the ovine uterus during the luteal regression phase of the oestrous
      cycle and post-blastocyst implantation in pregnancy and provide further evidence
      that GRP-related peptides have important regulatory roles in uterine function.

PMID- 9614368
TI  - Fetal endocrine responses to prolonged reduced uterine blood flow are altered
      following bilateral sectioning of the carotid sinus and vagus nerves.
AB  - The present study examines the effect of carotid sinus/vagosympathetic
      denervation on fetal endocrine responses to prolonged reduced uterine blood flow
      (RUBF). Fetal sheep had vascular catheters inserted following bilateral
      sectioning of the carotid sinus and vagus nerves (denervated, n = 7) or sham
      denervation (intact, n = 7). Uterine blood flow was mechanically restricted at
      126.1 +/- 0.7 days (mean +/- S.E.M.) for 24 h, decreasing arterial oxygen
      saturation by 47.3 +/- 2.6% (P < 0.01). Fetal plasma samples were obtained at -1,
      3, 6, 12 and 24 h for subsequent analyses of arginine vasopressin (AVP),
      angiotensin II and catecholamines. The AVP response to prolonged RUBF was
      markedly attenuated in denervated fetuses (15.6 +/- 3.6 to 34.9 +/- 6.0 pg/ml)
      when compared with intact (10.0 +/- 1.4 to 127.3 +/- 28.4 pg/ml). In contrast,
      intact fetuses demonstrated no change in plasma angiotensin II concentrations
      with RUBF whereas denervated fetuses demonstrated a marked increase from 47.5 +/-
      18.9 to 128.7 +/- 34.2 pg/ml. The norepinephrine and epinephrine responses to
      prolonged RUBF were attenuated in denervated fetuses (950.1 +/- 308.9 and 155.8
      +/- 58.5 to 1268.3 +/- 474.6 and 290.6 +/- 160.2 pg/ml respectively) when
      compared with intact (1558.3 +/- 384.4 and 547.3 +/- 304.7 pg/ml to 3289.2 +/-
      1219.8 and 896.8 +/- 467.8 pg/ml respectively). These results support a role for
      the peripheral chemoreceptors in mediating fetal endocrine responses to prolonged
      RUBF, which may in part lead to the altered cardiovascular responses observed in
      denervated fetuses under these conditions.

PMID- 9614369
TI  - Effects of active immunization of sheep against an amino terminal peptide of the
      inhibin alpha C subunit on intrafollicular levels of activin A, inhibin A and
      follistatin.
AB  - Active immunization of ewes against inhibin (IMM) consistently increases
      ovulation rate but this response is not always accompanied by the expected rise
      in plasma FSH. Inhibin-related molecules also have local auto/paracrine effects
      within the ovary and the ovulatory response to IMM could be due to neutralization
      of one of these effects, independent of changing FSH levels. To investigate this,
      ovaries were collected from long-term IMM (n = 6) and control (CON; n = 8) ewes
      killed 48 h after progestagen withdrawal (late follicular phase) and all
      follicles > or = 3 mm were recovered to determine intrafollicular levels of
      inhibin A, activin A and follistatin by specific two-site immunoassay and
      oestradiol and testosterone by radioimmunoassay. Blood samples were collected to
      assess plasma FSH, oestradiol and inhibin antibody titres. Although plasma FSH
      levels were similar in IMM and CON ewes, IMM ewes had approximately 3-fold more
      follicles > or = 3 mm (P < 0.0001) and approximately 3-fold more oestrogenic
      follicle (P < 0.001) than CON ewes. Compared with CON ewes, follicles from IMM
      ewes had much higher concentrations of activin A (approximately 6-fold; P <
      0.001) and inhibin A (approximately 3-fold; P < 0.001) but only slightly more
      follistatin (approximately 1.4-fold; not significant). The activin A:follistatin
      ratio in follicles from IMM ewes (approximately 1:1) was significantly higher (P
      < 0.001) than in follicles from CON ewes (approximately 0.3:1). Levels of inhibin
      antibody measured in follicular fluid (FF) from IMM ewes were similar to plasma
      levels. Given that activin A has been shown previously to up-regulate FSH
      receptors and aromatase activity in rat granulosa cells, the increase in
      intrafollicular activin A, unaccompanied by a rise in the concentration of its
      binding protein (follistatin), could explain how long-term IMM enhances follicle
      development and ovulation rate without necessarily promoting a sustained increase
      in FSH secretion.

PMID- 9614370
TI  - The lack of specificity of neuropeptide Y (NPY) antisense oligodeoxynucleotides
      administered intracerebroventricularly in inhibiting food intake and NPY gene
      expression in the rat hypothalamus.
AB  - To evaluate the role of neuropeptide Y (NPY), a potent appetite stimulant, in
      controlling food intake and body weight, we investigated the use of antisense
      oligodeoxynucleotides (ODNs) to inhibit NPY gene expression in the hypothalamus.
      We compared the hypothalamic distribution of fluorescein-labelled ODNs
      administered intracerebroventricularly, and effects on food intake and NPY gene
      expression, of three different structural modifications of an antisense ODN
      sequence against NPY. Rats had either the antisense or missense ODNs (24
      micrograms/day) or saline infused into the third ventricle by osmotic minipumps
      for 7 days. The unmodified phosphodiester ODN was not detectable in the
      hypothalamus after 7 days and had no effects on food intake. The phosphorothioate
      ODN was widely distributed throughout the hypothalamus but had nonselective
      effects, with similar changes in food intake and NPY mRNA levels in the antisense
      and missense groups, and was severely toxic. The propyl-protected ODN appeared to
      penetrate the hypothalamus well but had no antisense-selective effects on NPY
      mRNA levels or food intake. Antisense ODNs are increasingly used to inhibit gene
      expression in vitro and in intact animals. These negative findings underline the
      need for rigorous evaluation of any effects of antisense ODNs administered into
      the central nervous system, and raise doubts about the validity of this approach
      in physiological or pharmacological studies.

PMID- 9614371
TI  - Pulmonary adenocarcinoma: classification and molecular biology.
AB  - Pulmonary adenocarcinoma is increasing in incidence. Current classification
      systems based purely on morphological features are of little clinical relevance.
      Recent descriptions of genetic abnormalities, particularly in K-ras, p53, and c
      erb-B2, may form the basis of a new taxonomy having direct prognostic relevance.
      Study of these molecular lesions has also helped to define a new pathway of
      tumourigenesis in the lung parenchyma, through alveolar atypical hyperplasia
      (AAH) to clinical adenocarcinoma.

PMID- 9614372
TI  - The development of haematopathology laboratories: a possible model for other
      pathology services.
AB  - The diagnosis of haematological malignancies has undergone major conceptual
      changes in the past decade. Accurate diagnosis now depends on a combination of
      morphological examination, cell marker studies, and molecular biological
      techniques. Specialist haematopathology diagnostic services are best provided in
      an integrated laboratory, able to carry out the full range of techniques and
      staffed by pathologists and scientists with expertise in the investigation of
      leukaemia and lymphoma.

PMID- 9614373
TI  - Cytokeratins and cell differentiation in the pancreas.
AB  - Keratins, or cytokeratins, represent a family of more than 20 different
      polypeptides which are important markers of epithelial cell differentiation. This
      review deals with the use of keratin immunohistochemistry in the study of
      pancreatic cell differentiation. Exocrine acinar cells and endocrine islet cells
      are well-differentiated cells which express the keratin combination 8 and 18,
      whereas the less-differentiated cells of the ductal tree are characterized by the
      additional expression of keratin 7, keratin 19, and, in the rat, keratin 20.
      Keratin expression is stable and can be used for cell identification after
      isolation and culture, and in clinical or experimental injury. The intercalated
      ductal cells and centroacinar cells are inconspicuous unless specific
      immunohistochemical markers, such as keratins, are used. In conditions where
      there is morphogenetic differentiation such as in fetal life, or where
      transdifferentiation is occurring, keratins have been used to trace the origin
      and fate of pancreatic cells.

PMID- 9614374
TI  - FHIT and p53 gene abnormalities in bronchioloalveolar carcinomas. Correlations
      with clinicopathological data and K-ras mutations.
AB  - Bronchioloalveolar carcinoma (BAC) is a particular type of adenocarcinoma of the
      lung which accounts for up to 9 per cent of pulmonary malignancies. The aetiology
      and pathogenesis of this unique neoplastic disease are still unclear. Three
      histological subtypes of BAC have been recognized: mucinous, non-mucinous, and
      sclerosing. Of these, mucinous and sclerosing BAC have a worse prognosis than non
      mucinous tumours. The different morphological patterns and clinical outcomes of
      the subtypes of BAC suggest differences in their biological behaviour. Previous
      reports have shown that the mucinous form of BAC is characterized by constant
      mutations at codon 12 of the K-ras gene, whereas the other two histotypes show a
      frequency of K-ras mutations which is not different from that observed in
      conventional lung adenocarcinomas. The present study of a series of 51 BACs,
      previously investigated for K-ras gene mutations, has evaluated the status of two
      other genes, p53 and FHIT, known to be frequently altered in non-small cell lung
      cancer. Loss of heterozygosity at microsatellite-containing loci located within
      the FHIT gene was observed in 22 (43 per cent) BACs. The distribution of FHIT
      gene abnormalities was not statistically different in the three histological
      subtypes. p53 mutations were present in 13 (32 per cent) non-mucinous/sclerosing
      BACs, while no mutations were seen in mucinous tumours (P = 0.039). Correlations
      with clinicopathological parameters showed that p53 mutations in BACs are
      associated with more aggressive tumours. No correlations were observed between
      FHIT or K-ras gene abnormalities and clinicopathological data. In conclusion,
      these results indicate that FHIT alterations are frequently involved in BAC
      tumourigenesis and that genetic changes in the p53 and K-ras genes can
      distinguish between different histotypes of BAC.

PMID- 9614375
TI  - Expression of Bcl-2 in lung neuroendocrine tumours: comparison with p53.
AB  - Several genetic aberrations have been implicated in the carcinogenesis of small
      cell lung carcinomas (SCLCs), including tumour suppressor gene p53 deletion and
      mutation and amplification of the myc family proto-oncogenes. However, their
      exact ontogeny and carcinogenesis remain unknown. There are no proven
      aetiological factors for lung carcinoid tumours. Recent evidence suggests that
      the genetic regulation of apoptosis is of critical importance during
      tumourigenesis and that oncogene and tumour suppressor genes can regulate the
      rate, or susceptibility, of cells to undergo apoptosis. In this study, the
      expression of Bcl-2 protein has been investigated in 77 primary lung
      neuroendocrine tumours, including 55 SCLCs and 22 carcinoid tumours, and compared
      with p53 expression. Of the 77 tumours studied, Bcl-2 immunoreactivity was
      present in 80 per cent of SCLCs, 43 per cent of typical, and 67 per cent of
      atypical carcinoid tumours with more than 10 per cent tumour cell positivity.
      Western and Northern blot analysis revealed that carcinoid tumours expressed the
      26 kD protein and bcl-2 transcripts. Whereas 42 per cent of the SCLCs studied
      displayed p53 protein immunoreactivity in more than 10 per cent of tumour cells,
      p53 positivity was not found in lung carcinoid tumours. There are statistical
      differences in Bcl-2 and p53 expression between SCLCs and lung carcinoid tumours.
      These results suggest that disregulation of the genetic mechanisms controlling
      apoptosis is a critical step in the progression of SCLC, and the expression of
      Bcl-2 is involved in the pathogenesis of SCLC and lung carcinoid tumours. The
      genetic complementation of simultaneously deregulated Bcl-2 and p53 may be
      implicated in the multistep tumourigenesis of small cell lung cancer.

PMID- 9614376
TI  - SV40-like DNA sequences in pleural mesothelioma, bronchopulmonary carcinoma, and
      non-malignant pulmonary diseases.
AB  - Pleural and pulmonary malignancies are usually associated with well-known
      carcinogen exposure. Recently, the presence of simian virus 40 (SV40)-like DNA
      sequences has been detected in brain and bone-related human cancers and in
      pleural mesothelioma. In order to determine whether SV40-like DNA sequences are
      also present in bronchopulmonary carcinoma and non-malignant lung samples, 125
      frozen pleural and pulmonary samples (including 21 mesotheliomas, 63
      bronchopulmonary carcinomas, 8 other tumours, and 33 non-malignant samples) and
      38 additional samples distant from tumours were studied for the occurrence of
      SV40-like DNA sequences by polymerase chain reaction (PCR) amplification followed
      by hybridization with specific probes. Sequences related to SV40 large T antigen
      (Tag) were present in 28.6 per cent of bronchopulmonary carcinomas, 47.6 per cent
      of mesotheliomas, and 16.0 per cent of cases with non-neoplastic pleural and
      pulmonary disease. No statistically significant difference in the occurrence of
      these DNA sequences was found between malignant mesothelioma and bronchopulmonary
      carcinoma, but a significantly higher number of mesothelioma cases exhibited SV40
      like DNA sequences in comparison with cases of non-malignant pleural or pulmonary
      disease (P < 0.04). Among cases positive for SV40-like DNA sequences, a history
      of asbestos exposure was found in 3 out of 12 bronchopulmonary carcinomas and 8
      out of 10 mesotheliomas. Immunohistochemistry using monoclonal antibodies
      directed against Tag did not demonstrate nuclear staining. The DNA sequences were
      not related to BK virus sequences, but three samples were positive with probes
      hybridizing with JC virus DNA sequences. In conclusion, this study demonstrates
      the presence of SV40-like DNA sequences in pulmonary neoplasms and in non
      malignant lung tissues. It appears that the presence of SV40-like DNA is not
      unique to cancer.

PMID- 9614377
TI  - Decreased apoptosis in non-involved tissue from cancer-containing breasts.
AB  - Various histological changes in the breast have been associated with an increased
      risk of development of breast cancer; these changes have been identified in non
      involved tissue in cancer-containing breasts, suggesting that factors promoting
      the development of carcinoma may have a field effect. Previous work has
      identified alterations in growth factors receptors and integrins in cancer
      containing breast tissue. In the present study, proliferation and apoptosis are
      examined. Non-involved breast tissue from 104 women taken at least 4 cm away from
      a carcinoma and normal/benign tissue from 105 age-matched women were studied.
      Proliferation was assessed using MIB-1 immunohistochemistry and labelling for
      histone mRNA, as a marker of S-phase. In situ end-labelling was used to identify
      apoptosis; any non-labelled apoptotic bodies were also counted. No differences
      were found between the non-involved tissues and the control group for MIB-1 index
      and histone index. The apoptotic index was higher in the control group than in
      the cancer-containing breasts, being greater for ducts than for acini. When the
      apoptotic index/MIB-1 index and apoptotic index/histone index were considered,
      the mean for both was lower in the acini from cancer-containing breasts than in
      the control group, although the ratios for ducts were similar. The reduction in
      apoptosis may lead to the preservation of genetically aberrant cells, hence
      favouring neoplastic development. There is a need for further investigation of
      'at-risk' cases, including women with a family history, and for a prospective
      study of a large group of women.

PMID- 9614378
TI  - p21WAF1/Cip1 is associated with cyclin D1CCND1 expression and tubular
      differentiation but is independent of p53 overexpression in human breast
      carcinoma.
AB  - p21WAF1/Cip1 is an inhibitor of cdk/cyclin complexes, and thus regulates the cell
      cycle. p21 is also related to cell differentiation and is regulated by wild-type
      p53, although p53-independent regulatory pathways have been proposed. In order to
      analyse p21 expression as well as its relationship with p53 in human breast
      cancer, an immunohistochemical analysis was undertaken of 77 breast carcinomas,
      16 of them with an in situ component; 30 adjacent normal tissue samples; and five
      non-neoplastic specimens. Forty-four infiltrating carcinomas (57 per cent) were
      p21-positive. Expression of p21 was also observed in pre-invasive lesions,
      whereas normal ducts were negative or focally and weakly positive. p21 expression
      was associated with high histological grade (II + III) (P = 0.017) and poor
      tubule formation (P = 0.002), and was significantly less frequent in lobular
      carcinomas (P = 0.0001). p21 positivity also correlated with increased
      proliferation, but this seemed to be dependent on the histological grade. Twenty
      carcinomas (26 per cent) showed p53 overexpression, but this was not associated
      with p21 negativity, suggesting the existence of p53-independent mechanisms for
      p21 regulation in vivo. Cyclin D1CCND1 expression was analysed in the same series
      and an association between p21 and cyclin D1 expression was found, since 23 of 26
      cyclin D1-positive carcinomas were p21-positive (P < 0.001 ...). In conclusion,
      p21 is frequently overexpressed in breast carcinomas and this occurs in the early
      stages of neoplastic progression. This overexpression seems to be independent of
      p53 status and might be involved in cyclin D1 modulation.

PMID- 9614379
TI  - Expression of HNF-1 alpha and HNF-1 beta in various histological differentiations
      of hepatocellular carcinoma.
AB  - Hepatic nuclear factor 1 (HNF-1) regulates genes in a hepatocyte-specific manner.
      It has been previously reported that the ratio of HNF-1 alpha and HNF-1 beta mRNA
      is related to histological differentiation hepatocellular carcinoma (HCC). In
      this study, the expression levels of the HNF-1 alpha and HNF-1 beta proteins were
      analysed relatively and quantitatively in various histologically differentiated
      HCC and surrounding non-cancerous tissues, and HNF-1 alpha binding activity for
      the AT element of the B domain of the human alpha-fetoprotein enhancer was
      examined. Western blot analysis demonstrated that HNF-1 alpha protein was
      expressed at a higher level in well-differentiated HCC tissues than in the
      surrounding non-HCC tissues; on the other hand, the HNF-1 alpha protein was
      expressed at lower levels in moderately and poorly differentiated HCCs than in
      the surrounding non-HCC tissues. The levels of HNF-1 beta expression in well
      differentiated and poorly differentiated HCCs were similar to and higher than
      those found in the respective surrounding non-cancerous portions. In binding
      assays, HNF-1 binding activity was high in well-differentiated HCC and lower in
      moderately and poorly differentiated HCCs. Most well-differentiated HCC cases
      showed immunohistochemical expression of HNF-1 alpha. These findings show that
      poor histological differentiation of HCC correlates with decreases in the level
      and activity of HNF-1 alpha proteins.

PMID- 9614380
TI  - Induction of proliferating cell nuclear antigen and Ki-67 expression by
      cytomegalovirus infection.
AB  - With the goal of facilitating viral reproduction, cytomegalovirus (CMV) induces
      changes in the host cell replication machinery. Very little information is
      available, however, on the effects brought about by CMV on proliferating cell
      nuclear antigen (PCNA) and Ki-67 expression in infected cells. Fifty-five
      paraffin-embedded tissue samples (43 gastrointestinal, 10 skin, and 2 kidney
      biopsies) with both histological and immunohistochemical evidence of CMV
      infection were investigated for PCNA and Ki-67 expression by the avidinbiotin
      peroxidase method. Of the 55 cases studied, 47 were positive for PCNA and 46 for
      Ki-67. PCNA and Ki-67 immunostaining was more striking in CMV-immunoreactive,
      inclusion-free cell nuclei, whereas cell nuclei exhibiting well-developed CMV
      inclusions either showed a weak peripheral signal for both proliferation markers,
      or were completely negative. Enhanced PCNA and Ki-67 expression appears to be
      among the changes induced by CMV infection in host cells. Moreover, this
      induction seems to reach its peak during the earlier phases of CMV infection and
      abate as the infection proceeds to its inclusion-forming phases, when a
      sufficiently high viral load would have been attained.

PMID- 9614381
TI  - Correlation of T-helper secretory differentiation and types of antigen-presenting
      cells in squamous intraepithelial lesions of the uterine cervix.
AB  - This study addressed the notion that the progression of cervical cancer is
      associated with a T-helper 2 (TH2) immunodeviation by analysing cytokine
      expression in 60 cervical biopsy specimens, spanning the spectrum from normal
      cervical tissue to high-grade squamous intraepithelial lesions (SILs). The
      biopsies were analysed by immunohistochemistry for the expression of TH1
      [interleukin-2 (IL2), interferon gamma (IFN gamma)] and of TH2-type cytokines
      (IL4, IL6). Positive cells were usually observed in the subepithelial connective
      tissue, where most CD4+ cells were also detected. The density of IL2+ cells was
      significantly lower in high-grade SILs than in normal tissues taken either from
      the ectocervix or from the transformation zone. In contrast, significantly higher
      densities of IL4+ cells and, to a lesser degree, IL6+ cells were found in SIL
      biopsies compared with histologically normal tissues taken from the adjacent
      ectocervical region. A significantly higher IL4+/CD4+ cell ratio was also found
      in high-grade SILs (82 per cent) than in normal cervical biopsies taken from the
      transformation zone of healthy women showing squamous metaplasia (27 per cent).
      The elevated density of TH2+ cells in SIL biopsies was associated with both the
      expression of HLA-DR by keratinocytes and a diminished number of intraepithelial
      Langerhans' cells (CD1a+). In conclusion, the increased TH2+/CD4+ cell ratio in
      SIL biopsies suggest the presence, during cervical carcinogenesis, of a TH2
      immunodeviation that could participate in the immunoescape of preneoplastic
      cervical keratinocytes.

PMID- 9614382
TI  - Hyaluronate binding assay study of transfected CD44 V4-V7 isoforms into the human
      gastric carcinoma cell line SC-M1.
AB  - The potential human metastasis molecule CD44 and its isoforms V5 and V6 are
      overexpressed in human gastric carcinoma. Among the numerous extracellular matrix
      components, hyaluronate, a CD44 ligand, is of increasing interest in relation to
      its role in cancer cell development and invasion. By using the dynabead
      separation method, the SC-M1 cell line was separated into V5 and V6 isoform
      positive and -negative populations. The V5 and V6 isoform-negative populations
      exhibited significantly higher hyaluronate binding activity than the
      corresponding positive cells. The hyaluronate binding activity of V5 and V6
      positive cells could be restored by pretreatment with anti-CD44 V5 and V6
      monoclonal antibodies (MAbs). In addition, transfection of aVV5 and V6-negative
      cells decreased their hyaluronate binding activity to the levels of CD44 V5 and
      V6-positive cells. Cells transfected with V5 and V6 recovered their hyaluronate
      binding activity after pretreatment with MAbs against V5 and V6. These data
      suggest that cell adhesion involving hyaluronate can be regulated by multiple
      mechanisms, one of which involves alternative splicing of CD44 isoforms.

PMID- 9614383
TI  - CD44 expression in normal, hyperplastic, and malignant endometrium.
AB  - A total of 140 endometrial carcinomas (endometrioid type), as well as 72
      hyperplasias (41 of simple or complex and 31 of atypical type) and 141 normal
      endometria (35 in the proliferative and 106 in the secretory phase), were
      immunohistochemically investigated for expression of the standard and variant-3
      and -6 isoforms of CD44, and the results compared with several known prognostic
      factors. A combination of the reverse transcription-polymerase chain reaction (RT
      PCR) and Southern blot hybridization (SBH) for CD44 mRNA levels was also carried
      out on 27 endometrial carcinomas. In normal endometrium, the expression of
      standard and variant CD44 forms was remarkably higher in the secretory than in
      the proliferative phase, with immunoreactivity scores being inversely correlated
      with numbers of oestrogen and progesterone receptors. Significantly elevated
      levels of CD44 expression in endometrial carcinomas compared with the
      proliferative phase and hyperplasia were also revealed by both the
      immunohistochemical and the RT-PCR/SBH assays, while no association was noted
      with any prognostic factors. The results indicate that CD44 expression in the
      normal menstrual cycle is closely related to the secretory differentiation of the
      glandular epithelium. Moreover, detection of aberrant expression may be useful
      for the early diagnosis of endometrial carcinoma, but not as an indicator of
      tumour progression.

PMID- 9614384
TI  - Differential expression of collagen IV isoforms in experimental
      glomerulosclerosis.
AB  - Expansion of the glomerular mesangial matrix (MM), thickening of the glomerular
      basement membrane (GBM), and eventually the development of glomerulosclerosis are
      often seen in immunologically mediated kidney diseases. In addition to
      quantitative changes in the extracellular matrix (ECM), qualitative changes in
      ECM molecules may contribute to alterations in the composition of the glomerular
      matrix. The expression of collagen IV, alpha 1-5(IV) mRNA, and polypeptides was
      therefore investigated during the development of chronic graft-versus-host
      disease (GvHD) in mice, a model for lupus nephritis, and in chronic serum
      sickness (CSS) in rats, a model for membranous nephropathy. Immunohistochemical
      studies showed increased mesangial expression of alpha 1 and alpha 2 early in the
      disease, but only late in the GBM. In contrast, alpha 3 and alpha 4 increased in
      the GBM during disease, but not in the MM. The mRNA levels for all collagen IV
      chains were increased in isolated glomeruli before morphological alterations were
      detectable. The mRNA increase was earlier and more profound for alpha 3, alpha 4
      and alpha 5 than for alpha 1 and alpha 2. Expression of alpha 3(IV) was greatest
      in GvHD, whereas expression of alpha 4 was greatest in CSS. As determined by in
      situ hybridization (ISH), alpha 1 mRNA was observed dispersed in the glomerulus,
      but alpha 3, alpha 4, and alpha 5 mRNAs were mainly located in cells at the
      periphery of the glomerular tuft. The changes in the relative abundance of
      collagen IV mRNA in disease states may perturb the collagen IV network, altering
      glomerular structure and function, and may thereby play a central role in the
      development of glomerulonephritis and glomerulosclerosis.

PMID- 9614385
TI  - Effects of keratinocyte growth factor (KGF) on gut growth and repair.
AB  - Keratinocyte growth factor (KGF) is a mitogen found throughout the
      gastrointestinal tract, but its role in gastrointestinal pathophysiology is
      unclear. The effect of recombinant KGF on gut growth and repair has been examined
      using a variety of in vivo models. Rats receiving total parenteral nutrition had
      co-infusions of KGF or control for 6 days. Changes in gut growth (wet weight and
      vincristine-induced metaphase arrest) were then assessed. The effects of KGF on
      gastric repair and acid secretion in rats were determined using an indomethacin
      (20 mg/kg)/restraint model and animals fitted with chronic gastric fistulae. KGF
      at 0.1, 1, and 3 mg/kg increased gut growth as assessed by wet weight throughout
      the gastrointestinal tract and increased vincristine-induced accumulation of
      metaphases in the stomach and small intestine but not in the colon. Plasma
      gastrin, peptide YY, enteroglucagon, and glucagon-like peptide-1 were all
      increased, whereas insulin was lowered by KGF (all P < 0.01). KGF was ineffective
      in reducing indomethacin-induced gastric damage but caused a reduction in basal
      acid secretion of about 35 and 50 per cent when administered at 0.2 or 5 mg/kg (P
      < 0.05). These studies support the idea that KGF is involved in the control of
      proliferation of the gastrointestinal tract. They do not provide evidence,
      however, for a role in the early reparative process invoked during short-term
      models of gastrointestinal injury.

PMID- 9614386
TI  - Lack of inducible nitric oxide synthase in bronchial epithelium: a possible
      mechanism of susceptibility to infection in cystic fibrosis.
AB  - Cystic fibrosis (CF) is an inherited disorder associated with severe inflammation
      and repeated bacterial infection and colonization in the lung. Airway epithelium
      is involved in defence against bacteria, but this system may be defective in CF.
      Pro-inflammatory cytokines can stimulate the expression of inducible nitric oxide
      synthase (iNOS), an enzyme generating nitric oxide, which functions as an
      important mediator in host defence mechanisms. To understand better the poor
      resistance to infections in the CF lung, the expression of the iNOS gene was
      investigated in explanted lungs from patients with cystic fibrosis (n = 13),
      bronchiectasis (n = 3), emphysema (n = 14), and in normal lungs (n = 8). In
      addition, bronchial epithelial cell lines were examined to study iNOS gene
      expression in vitro. Strong immunoreactivity for iNOS was seen in inflammatory
      cells and bronchial epithelium in all the diseased lungs, except for bronchial
      epithelium in CF. Quantitative analysis showed a significant reduction in the
      area of epithelium immunostained in CF [CF 6.8 +/- 1.6 (% +/- SEM); emphysema
      18.2 +/- 2.8; normal 9.6 +/- 0.8, P < 0.01], regardless of steroid treatment.
      These results were supported by in situ hybridization of iNOS mRNA, which showed
      a pattern of gene expression in CF, emphysema, and normal lung which paralleled
      that of protein immunoreactivity. Stimulation with cytokines (IL-1 beta, TNF
      alpha, and IFN-gamma) increased the expression of iNOS mRNA detected by reverse
      transcriptase-polymerase chain reaction (RT-PCR) in cultures of normal (16HBE14o
      ), but not CF (CFBE41o-, with delta F508 CFTR mutation) epithelial cells.
      Expression of iNOS in inflammatory cells suggests that the gene is normal in CF.
      Absence of iNOS from bronchial epithelium may be due to low expression of the
      gene resulting from abnormalities in the signalling system that normally causes
      induction, such as cytokine receptors, second messengers or transcription
      factors. The resulting deficiency of the nitric oxide defence system may be
      relevant to the susceptibility of CF patients to pulmonary bacterial
      colonization.

PMID- 9614387
TI  - Extraction of RNA from single frozen sections.
AB  - The sensitivity of the reverse transcriptase-polymerase chain reaction (RT-PCR)
      makes it ideally suited for the detection of changes in gene expression.
      Unfortunately, traditional methods for RNA isolation require time-consuming
      procedures that are not appropriate for small samples, such as individual frozen
      sections. This report describes a new technique that permits the rapid extraction
      of RNA from individual frozen histological sections. RNA is extracted by
      incubating a frozen section in an RT-PCR compatible buffer solution containing
      RNase inhibitor and dithiothreitol. RNA isolated from frozen sections is stable
      at room temperature for up to 3 h under the conditions described. Alternatively,
      extracts can be frozen for later use. When maintained in a dry state at room
      temperature, RNA in sections remained stable for 2 weeks. Histological,
      immunohistochemical, or in situ analyses can be carried out with sections that
      are immediately adjacent to those used for extracting RNA. The simplicity and
      economy of this procedure may foster the development of prognostic screens that
      can be performed in parallel with traditional histopathological analysis.

PMID- 9614388
TI  - bcl-2 expression in synovial sarcoma.

PMID- 9614389
TI  - Ki-ras mutations in adenomas from cancer-bearing and cancer-free bowel.

PMID- 9614390
TI  - Dutch monitor on stress and physical load: risk factors, consequences, and
      preventive action.
AB  - OBJECTIVES: Due to recent changes in legislation on occupational health and
      safety, a national monitor on stress and physical load was developed in The
      Netherlands to monitor (a) risks and consequences of stress and physical load at
      work, (b) preventive actions in companies to reduce these risks, and (c)
      organisational and environmental variables that facilitate preventive actions.
      METHODS: Information was gathered from employers, employees, and employees'
      representatives. The monitor was used with a nationally representative sample of
      companies in industry, wholesale trade, and banking and finance, 782 companies in
      total. RESULTS AND CONCLUSIONS: The information from the employees, aggregated at
      the company level, was not found to be correlated with that from the employer
      from the same companies. Although many employers do recognise risk factors for
      both physical load and stress as a problem they often seem to underestimate the
      problem when compared with employees or their representatives. This is
      particularly the case for psychosocial risk factors. Also, the perception of
      outcome measures, especially employers who consider emotional exhaustion to be
      work related, were fewer than the employees' representatives of the same
      organisation. Preventive measures on physical load are much more popular than
      measures against stress. It is the responsibility of the employer to take more
      preventive action of all kinds. They need to recognise risk factors as problems
      and health outcomes to be related to work. Employees of larger companies should
      participate with employers to consider effective measures, and more use should be
      made of support at branch level. For specific preventive measures, specific
      predictors emerged. Except for measures to prevent work stress, information from
      employees did not sufficiently contribute to the initiation of preventive
      measures in the workplace.

PMID- 9614391
TI  - Psychosocial and physical risk factors associated with low back pain: a 24 year
      follow up among women and men in a broad range of occupations.
AB  - OBJECTIVES: To investigate the relation between psychosocial and physical factors
      at work, as well as conditions during leisure time, and low back pain (LBP) over
      24 years. METHODS: The study group consisted of 252 women and 232 men. From a
      previous study conducted in 1969, data on psychosocial and physical conditions
      and LBP were available. Data on LBP for 1971-93 were obtained retrospectively in
      1993. RESULTS: The prevalence of LBP in 1969 among women and men were 34% and
      24%, the cumulative incidences of LBP during 1970-92 were 38% and 43%, and the
      prevalences in 1993 of having had LBP during the past 12 months were 44% and 39%,
      respectively. Monotonous work and few or unsatisfactory social contacts outside
      work were risk factors for LBP in 1969 among women. LBP in 1969 and
      dissatisfaction with leisure time were risk factors among both sexes for LBP in
      1970-92. LBP in 1969 was a risk factor for LBP in 1993 among women and
      dissatisfaction with leisure time a risk factor among men. Interactions between
      few or unsatisfactory social contacts outside work, as well as dissatisfaction
      with leisure time, and several factors related to work were found to increase the
      risk of LBP among both sexes during the studied periods. CONCLUSIONS: Conditions
      in leisure time exert a long term influence on LBP. In this study factors related
      to work had a long term effect only in interaction with leisure time factors.

PMID- 9614392
TI  - Socioeconomic and sex differentials in reason for sickness absence from the
      Whitehall II Study.
AB  - OBJECTIVES: Large socioeconomic differences exist in disease and mortality. This
      paper describes the distribution of specific medical reasons for sickness absence
      by grade of employment in the Whitehall II study and validates the medical reason
      by comparison with general practitioners' records. METHODS: Analysis of sickness
      absence data on 5620 male and female civil servants aged 35-55 years. Data have
      been collected from 12 of the 20 London based civil service departments
      participating in the Whitehall II study, where medical reason for absence was
      available. Rates and distributions of reasons for absence for short spells (< or
      = 7 days) and long spells (> 7 days) were analysed. RESULTS: Respiratory
      disorders and gastroenteritis accounted for over half of all spells of absence,
      with headache and migraine, musculoskeletal disorders, injury, and neurosis
      accounting for a further 20%-30% of absences. There was an inverse association
      with employment grade, the lower the grade the higher the rate of absence for
      both short spells (< or = 7 days) and long spells (> 7 days). In general, women
      had higher rates of absence than men. Comparison of reason for very long spells
      of absence (> 21 days) showed moderate agreement between civil service and
      general practitioner. CONCLUSION: There is a lack of national comprehensive data
      on sickness absence and medical reason for absence, in particular for women and
      for spells of different duration. Data from the Whitehall II study show large
      employment grade and sex differences in the distribution of medical reasons for
      absence that are similar to socioeconomic differences in morbidity documented in
      other studies. Possible explanations include the subjective nature of illness and
      disease; the work/family interface; and the influence of the absence culture.
      Longer term follow up will provide information on whether sickness absence
      relates to serious morbidity and mortality.

PMID- 9614393
TI  - Are long working hours and shiftwork risk factors for subfecundity? A study among
      couples from southern Thailand.
AB  - OBJECTIVE: To estimate the effect of long working hours and shift work on time to
      pregnancy. METHODS: Cross sectional samples with retrospective data collection
      from two 700 bed hospitals at secondary to tertiary care level in Hatyai
      district, Songkhla Province, Thailand. The study was conducted from March 1995 to
      November 1995 among 1496 pregnant women attending the antenatal clinics.
      Subfecundity was defined as time to pregnancy longer than 7.8, 9.5, or 12 months
      (time to pregnancy was calculated from the date at which the couples started
      having sexual relations without any contraception until last menstrual date).
      RESULTS: The descriptive analyses were restricted to 1201 planned pregnancies and
      the analytical part to 907 working women. Separate analyses on primigravid women
      were also done. Logistic regressions adjusted for age, education, body mass
      index, menstrual regularity, obstetric and medical history, coital frequency, and
      potential exposure to reproductive toxic agents, showed an odds ratio (OR)
      associated with female exposure to long working hours of 2.3 (95% confidence
      interval (95% CI) 1.0 to 5.1) in primigravid and 1.6 (1.0 to 2.7) in all pregnant
      women. Male exposure to long working hours and shiftwork showed no association
      with subfecundity. The OR of subfecundity was highest when both partners worked >
      70 hours a week irrespective of the cut off point used (OR 4.1 (95% CI 1.3 to
      13.4) in primigravid women; OR 2.0 (95% CI 1.1 to 3.8) in all pregnant women).
      CONCLUSIONS: Long working hours is a risk factor for subfecundity especially for
      women. Shiftwork was not associated with subfecundity in this study.

PMID- 9614394
TI  - Adult myeloid leukaemia, geology, and domestic exposure to radon and gamma
      radiation: a case control study in central Italy.
AB  - OBJECTIVES: To investigate whether indoor randon or gamma radiation might play a
      part in myeloid leukaemia as suggested by studies based on crude geographical or
      geological data for exposure assessment. METHODS: For six months randon and gamma
      radiation was measured with solid state nuclear track detectors and
      thermoluminescent dosimeters in dwellings of 44 adult male cases of acute myeloid
      leukaemia and 211 controls (all subjects deceased). Conditional logistic
      regression ORs (ORs) and 95% confidence intervals (95% CIs) were estimated for
      quartiles of radon and gamma radiation and for municipality and dwelling
      characteristics. RESULTS: The risk of leukaemia was associated with an increasing
      urbanisation index (p value for trend = 0.008). An increased OR was found among
      those living in more modern houses (OR 3.0, 95% CI 1.4 to 6.6). Confirming the
      findings of a previous study in the same area, geological features bore a
      positive association with myeloid leukemia, even by adjusting for level of
      urbanisation. Contrary to expectations from the previous study, however, no
      association appeared between myeloid leukaemia and radon and gamma radiation; for
      the highest quartiles of exposure, ORs were 0.56 (95% CI 0.2 to 1.4) and 0.52
      (95% CI 0.2 to 1.4), respectively. Considering only subjects who had lived > or =
      20 years in the monitored home and adjusting for urbanisation, there was still no
      effect of exposure to radiation. CONCLUSIONS: In view of the limited numbers, the
      results do not in general refute a possible risk of myeloid leukaemia from
      exposure to indoor radon or gamma radiation, but decrease the credibility of such
      a relation in the area studied and also of other studies suggesting an effect
      without monitoring indoor radiation. Some other fairly strong determinants have
      appeared--that is, level of urbanisation and living in modern houses--that might
      need further consideration.

PMID- 9614395
TI  - Mortality from lung cancer and population risk attributable to asbestos in an
      asbestos cement manufacturing town in Italy.
AB  - OBJECTIVE: To estimate mortality from lung cancer and the risk attributable to
      asbestos separately for asbestos cement workers and for the general (non
      occupationally exposed) population in the town of Casale Monferrato, where the
      largest Italian asbestos cement factory had been in operation in 1907-86.
      According to cancer registry data, in the same town the incidence of malignant
      mesothelioma in the general population is about 10 times higher than in
      comparable Italian provinces. METHOD: Decedents from lung cancer in 1989-95 were
      nominally identified in the list of decedents kept at the Local Health Authority
      of Casale Monferrato. Workers in the asbestos cement factory have been identified
      with a search in the nominal list of workers and the same was done for the wives
      of asbestos cement workers. These lists have already been used in cohort studies.
      Sensitivity and specificity of the linkage procedure with occupational activity
      in asbestos cement production have been evaluated in a previous study. Population
      at risk was estimated on the basis of official figures and on the results of the
      cohort study of asbestos cement workers. RESULTS: 227 deaths from lung cancer
      were included (184 men and 43 women). Among the asbestos cement workers
      mortalities were 234.0 x 100,000 person-years among men and 35.5 among women.
      Corresponding figures in the general (non-occupationally exposed) population in
      Casale Monferrato were 80.6 and 18.7. The rates in the general population were
      not higher than in the rest of the region. Attributable risk (AR) among the
      asbestos cement workers (and wives) is 67.5% (95% confidence interval (95% CI)
      56.8 to 78.2) for men and 51.3% (95% CI 14.9 to 87.8) among women. Population AR
      to occupational or paraoccupational exposure in the asbestos cement production is
      18.3% (95% CI 11.1 to 25.6) among men and 10.1% (95% CI 0 to 24.6) among women.
      CONCLUSION: This work did not show an increase in mortality from lung cancer for
      the population not exposed occupationally, but a large excess was found among men
      and women occupationally exposed in asbestos cement production. The total burden
      of lung cancer due to occupational exposure to asbestos may be underestimated, as
      only occupational exposure in asbestos cement production was taken into
      consideration. Nevertheless even a single factory can be responsible for a
      considerable proportion of deaths from lung cancer in a population.

PMID- 9614396
TI  - Increased risk of lung cancer among different types of professional drivers in
      Denmark.
AB  - OBJECTIVES: To study risk of lung cancer among groups of professional drivers
      probably exposed to different levels of traffic exhaust fumes. METHODS: A
      nationwide case-control study (1970-89) based on employees comprising 28,744 men
      with primary lung cancer and incidence density sampled matched controls (1:1).
      Employment histories were reconstructed back to 1964 for each study subject from
      the records of a nationwide pension scheme with compulsory membership.
      Socioeconomic status was derived from the individual job title taken from the
      national population registry. Information on tobacco smoking habits was available
      from historical surveys. Relative risks were estimated by odds ratios (ORs) based
      on conditional logistic regression analyses. RESULTS: In total 2251 of the male
      lung cancer cases had been employed as bus, lorry, taxi, or unspecified drivers.
      No significant difference in tobacco smoking habits was found among professional
      male Danish drivers and the total employed population. The OR for lung cancer
      adjusted for socioeconomic status was 1.6 (95% confidence interval (95% CI) 1.2
      to 2.2) among taxi drivers, who were considered to be exposed to the highest
      concentrations of vehicle exhaust fumes, and 1.3 (1.2 to 1.5) for bus and lorry
      drivers. The OR was 1.4 (1.3 to 1.5) for unspecified drivers. The adjusted risk
      of lung cancer increased significantly with increasing duration of employment as
      a driver, and the risk was highest for long term taxi drivers with 10 years of
      lag time (OR 3.0; 1.2 to 6.8). CONCLUSION: Occupational factors, probably
      exposure to vehicle exhaust, seems to play an important part in the development
      of lung cancer among drivers.

PMID- 9614397
TI  - Stepwise health surveillance for bronchial irritability syndrome in workers at
      risk of occupational respiratory disease.
AB  - OBJECTIVES: Questionnaires, lung function tests, and peak flow measurements are
      widely used in occupational health care to screen for subjects with respiratory
      disease. However, the diagnostic performance of these tests is often poor.
      Application of these tests in a stepwise manner would presumably result in a
      better characterisation of subjects with respiratory disease. METHODS: Cross
      sectional data from workers exposed to acid anhydrides, to laboratory animals,
      and to flour dusts were used. Sensitivity and specificity were calculated from
      cross tables of different (combinations of) tests for bronchial
      hyperresponsiveness and bronchial irritability in the past four weeks (BIS). From
      sensitivity and specificity likelihood ratios were computed and change in
      probability of BIS was calculated. RESULTS: The prevalence of BIS was 7%, 7%, and
      5%, respectively. In all groups questionnaire data provided excellent sensitivity
      but poor specificity, which was inherent on the broad definition of symptoms.
      Adding the forced expiratory volume in one second/forced vital capacity
      (FEV1/FVC) ratio yields almost perfect specificity, and peak expiratory flow
      (PEF) variability is intermediate in populations in which smoking induced or non
      allergic respiratory diseases predominates. In occupational groups in which
      asthma is a problem, adding PEF measurements will optimise sensitivity and
      specificity in detection of BIS. The probability of BIS for subjects with a
      negative combined test outcome was lower than the probability before testing.
      Subjects with a positive combined test outcome had a probability of BIS after the
      tests at least three times the probability before. CONCLUSIONS: Combined testing
      yields better sensitivity and specificity. An advantage of combined testing is an
      economy in the effort to screen for subjects with BIS. Combined testing resulted
      in more detailed estimation of the probability of BIS.

PMID- 9614398
TI  - Dioxin exposure and non-malignant health effects: a mortality study.
AB  - OBJECTIVE: To investigate, in a population heavily exposed to 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD), the possible unusual occurrence of diseases
      other than cancer. METHODS: Five year extension of the follow up of the cohort
      involved in the Seveso accident. Soil measurements identified three exposure
      zones: (A) highest contamination, (B) substantial, and (R) low but higher than
      background contamination. Blood TCDD measurements, although limited in number,
      confirmed zone exposure ranking. The 15 year mortality in the exposed cohort was
      compared with that of a large population in the surrounding non-contaminated
      territory. Relative risks (RRs) and 95% confidence intervals (95% CIs) were
      estimated with Poisson regression techniques. RESULTS: The already noted
      increased occurrence of cardiovascular deaths was confirmed, in particular in
      zone A, among males for chronic ischaemic heart disease (five deaths, RR 3.0, 95%
      CI 1.2 to 7.3), and among females for hypertensive disease (three deaths, RR 3.6,
      95% CI 1.2 to 11.4) and chronic rheumatic heart disease. Novel findings were the
      increase of chronic obstructive pulmonary disease, most notably among males in
      zone A (four deaths, RR 3.7, 95% CI 1.4 to 9.9) and females in zone B (seven
      deaths, RR 2.4, 95% CI 1.1 to 5.1); and from diabetes, which was significantly
      increased in females in zone B (13 deaths, RR 1.9, 95% CI 1.1 to 3.2). In zone R,
      chronic ischaemic heart disease (males and females), hypertension (females), and
      diabetes (females) showed less pronounced, although significant excesses.
      CONCLUSIONS: As well as high TCDD exposure, the accident caused a severe burden
      of strain in the population. Both these factors might have contributed to the
      noted increased risks (in particular, circulatory and respiratory). The
      cardiovascular and immune toxicity of TCDD, as well as its complex interaction
      with the endocrine system, might be relevant to the explanations of these
      findings. These results, although not conclusive, concur with previous data in
      suggesting cardiopulmonary and endocrine effects in humans highly exposed to
      TCDD.

PMID- 9614399
TI  - Influence of biological and analytical variation on urine measurements for
      monitoring exposure to cadmium.
AB  - OBJECTIVE: To define the mean intraindividual biological variation in urinary
      concentrations of cadmium and retinol binding protein (RBP) in untimed, random
      urine samples and the influence of creatinine or specific gravity correction on
      reducing this variation. The relation between biological variation and analytical
      variation in defining uncertainty in a single measurement and significant
      differences between successive measurements was explored. METHODS: Repeat
      measurement study in subjects with either high historical exposure to cadmium but
      without current exposure, or unexposed volunteers. Standard statistical tools
      used in clinical laboratory medicine were applied to define intraindividual
      biological and analytical variation. RESULTS AND CONCLUSION: Both creatinine and
      specific gravity correction of urinary cadmium measurements in random urine
      samples seem to reduce the intraindividual variability compared with uncorrected
      values. With a standard definition, acceptable long term analytical precision for
      measurements of cadmium and RBP combined with creatinine analyses should be < 9%
      and < 15% respectively. The mean intraindividual biological variation of cadmium
      and RBP, expressed as creatinine corrected, was 18% and 40% respectively in the
      subjects exposed to cadmium. With the analytical precision used, significant
      differences (p < 0.05) between consecutive measurements for creatinine corrected
      urinary cadmium and RBP would need to show changes of > 54% and > 110%
      respectively. The relation between significant differences in consecutive results
      and differences in the analytical precision of the method used to measure the
      samples is described.

PMID- 9614400
TI  - Urinary excretion of platinum from platinum industry workers.
AB  - OBJECTIVES: Assessment of level of exposure to platinum and platinum
      concentration in urine from platinum industry workers to evaluate internal
      exposures and excretion kinetics. METHODS: Platinum concentrations in urine
      samples from 34 workers were measured by adsorptive voltammetry after UV
      photolysis. Morning and evening samples were taken two to six times during six
      months. Individual exposures were assessed by personal air sampling. Also, two
      male volunteers were exposed to platinum dust for four hours at a typical
      platinum refinery workplace. RESULTS: Urinary platinum excretion after a shift in
      platinum industry workers was found to be up to 6270 ng/g creatinine--that is,
      1000 times above the median value of unexposed people. Urinary excretion reached
      the maximum nearly 10 hours after inhalative exposure to dust containing
      platinum. Elimination corresponded to a first half life of about 50 (95%
      confidence interval (95% CI) 36 to 66) hours, but there were indications that a
      part of the incorporated platinum is stored longer. The amount of urinary
      platinum excretion showed a close correlation with the exposure level monitored
      by personal air sampling. CONCLUSIONS: A newly developed analytical method
      enabled the detection of even natural background concentrations of platinum.
      Thus, increased urinary platinum concentrations could be detected early, which is
      important to avoid damaging health of exposed workers.

PMID- 9614401
TI  - Diver's hand: a skin disorder common in occupational saturation diving.
AB  - Saturation divers regularly inspect North Sea installations, working at depth for
      periods of 12-16 days. Diver's hand is a particular problem in saturation diving,
      and there is no effective protection or treatment available. This paper presents
      the occurrence of diver's hand and describes the disease in clinical and
      epidemiological terms. Three studies of diver's hand have been carried out, in
      1990, 1994, and 1995. Most long term saturation divers have had diver's hand at
      some time in their professional career. Diver's hand seems able to occur without
      any previous skin symptoms, and divers without diver's hand can have several
      other skin symptoms during a saturation period. It is likely that diver's hand is
      a specific phenomenon associated with saturation diving.

PMID- 9614402
TI  - Inhalation of ammonium nitrate fuel oil explosive (ANFO)

PMID- 9614403
TI  - Effects of acute exposure to ultrahigh radiofrequency radiation on three antenna
      engineers.

PMID- 9614404
TI  - Panic disorder: diagnosis and treatment in primary care.

PMID- 9614405
TI  - Diagnosis of urinary tract infection in children.

PMID- 9614406
TI  - Pneumococcal vaccination in elderly and at-risk patients.

PMID- 9614407
TI  - Paresthesias.

PMID- 9614408
TI  - Reflex sympathetic dystrophy.

PMID- 9614409
TI  - Chronic bronchitis: primary care management.
AB  - Chronic bronchitis is a clinical diagnosis characterized by a cough productive of
      sputum for over three months' duration during two consecutive years and the
      presence of airflow obstruction. Pulmonary function testing aids in the diagnosis
      of chronic bronchitis by documenting the extent of reversibility of airflow
      obstruction. A better understanding of the role of inflammatory mediators in
      chronic bronchitis has led to greater emphasis on management of airway
      inflammation and relief of bronchospasm. Inhaled ipratropium bromide and
      sympathomimetic agents are the current mainstays of management. While
      theophylline has long been an important therapy, its use is limited by a narrow
      therapeutic range and interaction with other agents. Oral steroid therapy should
      be reserved for use in patients with demonstrated improvement in airflow not
      achievable with inhaled agents. Antibiotics play a role in acute exacerbations
      but have been shown to lead to only modest airflow improvement. Strengthening of
      the respiratory muscles, smoking cessation, supplemental oxygen, hydration and
      nutritional support also play key roles in long-term management of chronic
      bronchitis.

PMID- 9614410
TI  - Office care of the premature infant: Part II. Common medical and surgical
      problems.
AB  - Medical problems associated with prematurity are frequently complex, and a
      multidisciplinary approach is often required. Some common problems include the
      following: (1) anemia, which can be reduced by iron supplementation, (2) cerebral
      palsy or mental retardation as a result of intraventricular hemorrhage or
      periventricular leukomalacia, (3) respiratory problems, including
      bronchopulmonary dysplasia and apnea, (4) visual problems, such as those
      associated with retinopathy of prematurity, (5) gastroesophageal reflux and (6)
      surgical problems, including inguinal or umbilical hernia and cryptorchidism.
      Monitoring of growth and development includes recording the infant's head
      circumference, weight and length on a growth chart for premature infants.
      Nutritional status should be assessed at each visit, watching for hyperosmolar
      problems in infants receiving high-calorie formulas. Consultation with other
      specialists may be required if abnormalities are identified during follow-up care
      in the office.

PMID- 9614411
TI  - Panic disorder: effective treatment options.
AB  - Panic disorder is a distressing and debilitating condition with a familial
      tendency; it may be associated with situational (agoraphobic) avoidance. The
      diagnosis of panic disorder requires recurrent, unexpected panic attacks and at
      least one of the following characteristics: persistent concern about having an
      additional attack (anticipatory anxiety); worry about the implications of an
      attack or its consequences (e.g., a catastrophic medical or mental consequence)
      and making a significant change in behavior as a consequence of the attacks. A
      variety of pharmacologic interventions is available, as are non-pharmacologic
      cognitive or cognitive-behavioral therapies that have demonstrated safety and
      efficacy in the treatment of panic disorder. Early detection and thoughtful
      selection of appropriate first-line interventions can help these patients, who
      often have been impaired for years, regain their confidence and ability to
      function in society.

PMID- 9614412
TI  - Skin and wound infections: an overview.
AB  - Skin infections are common and may be caused by bacteria, fungi or viruses.
      Breaks in the skin integrity, particularly those that inoculate pathogens into
      the dermis, frequently cause or exacerbate skin infections. Bacterial skin
      infections caused by corynebacteria include erythrasma, trichomycosis axillaris
      and pitted keratolysis. Staphylococci may cause impetigo, ecthyma and
      folliculitis. Streptococcal skin infections include impetigo and erysipelas.
      Human papillomavirus skin infections present as several different types of warts,
      depending on the surface infected and its relative moisture, and the patterns of
      pressure. The many dermatomycoses (skin infections caused by fungi or yeasts)
      include tinea capitis, tinea barbae, tinea cruris, tinea manus, tinea pedis and
      tinea unguium (onychomycosis). Candidal infections occur in moist areas, such as
      the vulva, mouth, penis, skinfolds and diaper area. Wounds caused by wood
      splinters or thorns may result in sporotrichosis. Animal bites may result in
      complex, serious infections, requiring tetanus and, possibly, rabies prophylaxis
      in addition to appropriate antibiotic therapy.

PMID- 9614413
TI  - Urinary tract infections in children: why they occur and how to prevent them.
AB  - Urinary tract infections (UTIs) usually occur as a consequence of colonization of
      the periurethral area by a virulent organism that subsequently gains access to
      the bladder. During the first few months of life, uncircumcised male infants are
      at increased risk for UTIs, but thereafter UTIs predominate in females. An
      important risk factor for UTIs in girls is antibiotic therapy, which disrupts the
      normal periurethral flora and fosters the growth of uropathogenic bacteria.
      Another risk factor is voiding dysfunction. Currently, the most effective
      intervention for preventing recurrent UTIs in children is the identification and
      treatment of voiding dysfunction. Imaging evaluation of the urinary tract
      following a UTI should be individualized, based on the child's clinical
      presentation and on clinical judgment. Both bladder and upper urinary tract
      imaging with ultrasonography and a voiding cystourethrogram should be obtained in
      an infant or child with acute pyelonephritis. Imaging studies may not be
      required, however, in older children with cystitis who respond promptly to
      treatment.

PMID- 9614414
TI  - Preterm labor: diagnosis and treatment.
AB  - Preterm labor and delivery are among the most challenging obstetric complications
      encountered by the family physician. In the United States, preterm delivery
      affects approximately one in 10 births and is the cause of at least 75 percent of
      neonatal deaths, excluding those related to congenital malformations. Although
      the cause of preterm labor is unknown, family physicians who provide obstetric
      care should familiarize themselves and their patients with the predisposing risk
      factors. Preconception counseling should emphasize family planning, nutrition,
      "safe sex techniques", treatment of sexually transmitted diseases, and avoidance
      of cigarettes, alcohol, abusive drugs and harmful work conditions. The rate of
      fetal morbidity can be reduced with the early and accurate diagnosis of preterm
      labor, intervention to delay preterm delivery, administration of corticosteroids
      and provision of neonatal care. Research into biochemical markers such as fetal
      fibronectin, possible infectious etiologies such as bacterial vaginosis, and the
      use of more selective tocolytic therapy offers hope that new therapeutic
      approaches may increase rates of fetal survival.

PMID- 9614415
TI  - Diagnosis and management of the adnexal mass.
AB  - Adnexal masses are frequently found in both symptomatic and asymptomatic women.
      In premenopausal women, physiologic follicular cysts and corpus luteum cysts are
      the most common adnexal masses, but the possibility of ectopic pregnancy must
      always be considered. Other masses in this age group include endometriomas,
      polycystic ovaries, tubo-ovarian abscesses and benign neoplasms. Malignant
      neoplasms are uncommon in younger women but become more frequent with increasing
      age. In postmenopausal women with adnexal masses, both primary and secondary
      neoplasms must be considered, along with leiomyomas, ovarian fibromas and other
      lesions such as diverticular abscesses. Information from the history, physical
      examination, ultrasound evaluation and selected laboratory tests will enable the
      physician to find the most likely cause of an adnexal mass. Measurement of serum
      CA-125 is a useful test for ovarian malignancy in postmenopausal women with
      pelvic masses. Asymptomatic premenopausal patients with simple ovarian cysts less
      than 10 cm in diameter can be observed or placed on suppressive therapy with oral
      contraceptives. Postmenopausal women with simple cysts less than 3 cm in diameter
      may also be followed, provided the serum CA-125 level is not elevated and the
      patient has no signs or symptoms suggestive of malignancy.

PMID- 9614416
TI  - Pseudoneurologic syndromes: recognition and diagnosis.
AB  - Physicians may encounter patients with a collection of psychologic disorders that
      present with neurologic symptoms or signs, yet have no identifiable structural or
      functional etiology within the nervous system. These disorders comprise the so
      called pseudoneurologic syndromes, which can mimic almost any organic disease. A
      careful history and physical examination often can identify the psychologic
      origin of the symptoms. Presenting syndromes can include pseudoparalysis,
      pseudosensory syndromes, pseudoseizures, pseudocoma, psychogenic movement
      disorders and pseudoneuro-ophthalmologic syndromes. These presentations may be
      distinguished from organic disease by observing signs and symptoms or eliciting
      test responses that are nonphysiologic and incompatible with organic disease.
      Once a pseudoneurologic syndrome is identified, patients require compassionate
      and understanding care to resolve underlying emotional problems.

PMID- 9614417
TI  - NIH issues consensus statement on acupuncture.

PMID- 9614418
TI  - ACOG releases practice pattern on shoulder dystocia.

PMID- 9614420
TI  - The politics of EPSDT policy in the 1990s: policy entrepreneurs, political
      streams, and children's health benefits.
AB  - The Early and Periodic Screening, Diagnosis and Treatment (EPSDT) program, which
      was designed to ensure that Medicaid-eligible children receive comprehensive
      health services, is the only national attempt to provide a right to these
      services. The political factors that have shaped national EPSDT policy during the
      past decade are described, based on a conceptual framework developed by John W.
      Kingdon. The analysis focuses on the roles of two distinct sets of policy
      entrepreneurs: child health advocates and fiscally conservative governors. Their
      activities are described in relation to the larger political environment, or
      "political stream," from the period of the expansion of Medicaid eligibility for
      pregnant women and children in the late 1980s to the enactment of a new State
      Children's Health Insurance Program (SCHIP) in 1997. The relative saliency of
      eligibility and benefit issues in children's health policies had a major
      influence on the politics and outcomes.

PMID- 9614419
TI  - Evaluating community efforts to decategorize and integrate financing of
      children's health services.
AB  - Publicly funded categorical programs for children often differ in eligibility
      rules, allowable services, and criteria for provider participation, making it
      necessary for families to navigate through several programs to piece together
      care for their children. Recognizing these problems, the Robert Wood Johnson
      Foundation launched a national demonstration project in 1991 with the goal of
      decategorizing children's health services in nine communities. It was hoped that
      by releasing funds from categorical restrictions on their use, scarce public
      resources could be directed where they might have the greatest impact. However,
      the demonstration sites confronted a number of challenges in designing and
      implementing decategorization strategies: an absence of existing models and
      effective technical assistance; political hurdles in gaining cooperation from the
      multiple local agencies engaged in service provision; and difficulties in
      carrying out major programmatic changes when the health care system itself was
      rapidly being transformed. The proposition that decategorization holds promise as
      a tool for improving access to health care deserves further investigation.

PMID- 9614421
TI  - The use of EPSDT and other health care services by children enrolled in Medicaid:
      the impact of OBRA'89.
AB  - To increase the participation of Medicaid children in the Early and Periodic
      Screening, Diagnosis and Treatment (EPSDT) program and to improve their health,
      Congress included several provisions in the Omnibus Budget Reconciliation Act of
      1989 (OBRA'89) that addressed problematic program features. The impact of these
      provisions on children's health service use was investigated in a study funded by
      the Health Care Financing Administration. After conducting site visits to four
      states, the authors analyzed claims data for the children residing there and
      found evidence that, in 1992, these states placed a higher priority on improving
      the effectiveness of EPSDT than they did before 1989. The states' efforts to
      expand the EPSDT provider base and to enhance outreach and service provision were
      either directly or indirectly inspired by OBRA'89. The authors also found
      evidence of a significant impact on provider participation and caseloads and on
      children's use of both preventive care and diagnostic and treatment services.
      However, the effects were modest in comparison to the size of the progress that
      is required.

PMID- 9614422
TI  - Beyond managing Medicaid costs: restructuring care.
AB  - The apparent success of managed care plans in controlling medical costs has made
      the prospect of managed care for Medicaid recipients attractive for state health
      policy makers. However, because the principles upon which managed care was
      created do not apply to the most costly segments of the Medicaid population,
      efforts to address their needs through traditional managed care strategies are
      likely to be self-defeating. The Maryland Medicaid database was used to review
      and analyze the successes and failures of managed care Medicaid initiatives to
      date. This review led to the suggestion that the integration of specialized
      systems for specific subgroups of the Medicaid population into managed care, in
      conjunction with broader public policies, could lead to improved quality and
      lower costs.

PMID- 9614423
TI  - Public trust and initiatives for new health care partnerships.
AB  - Effective communication between doctor and patient is a critical component of
      high-quality care. The physician's credibility has a significant effect on
      treatment outcomes. Because changes in medicine and larger cultural trends
      challenge the ability of clinicians to engage their patients' trust, new kinds of
      partnerships must be created. To do this effectively, physicians have to sharpen
      their communication skills and devise strategies for assuring that their patients
      become informed allies in their own treatment. A number of innovations are
      helping to build these alliances: training in communication skills; creative uses
      of the Internet and videotape technologies; improved "customer service" programs;
      critical pathways for patients; and special educational aids. All these tools
      promise to be useful, but they require careful development and evaluation.

PMID- 9614424
TI  - Screening for elevated blood lead levels. American Academy of Pediatrics
      Committee on Environmental Health.
AB  - Although recent data continue to demonstrate a decline in the prevalence of
      elevated blood lead levels (BLLs) in children, lead remains a common,
      preventable, environmental health threat. Because recent epidemiologic data have
      shown that lead exposure is still common in certain communities in the United
      States, the Centers for Disease Control and Prevention recently issued new
      guidelines endorsing universal screening in areas with > or = 27% of housing
      built before 1950 and in populations in which the percentage of 1- and 2-year
      olds with elevated BLLs is > or = 12%. For children living in other areas, the
      Centers for Disease Control and Prevention recommends targeted screening based on
      risk-assessment during specified pediatric visits. In this statement, The
      American Academy of Pediatrics supports these new guidelines and provides an
      update on screening for elevated BLLs. The American Academy of Pediatrics
      recommends that pediatricians continue to provide anticipatory guidance to
      parents in an effort to prevent lead exposure (primary prevention). Additionally,
      pediatricians should increase their efforts to screen children at risk for lead
      exposure to find those with elevated BLLs (secondary prevention).

PMID- 9614425
TI  - Neonatal drug withdrawal. American Academy of Pediatrics Committee on Drugs.
AB  - Maternal drug use during pregnancy may result in neonatal withdrawal. This
      statement presents current information about the clinical presentation,
      differential diagnosis, therapeutic options, and outcome for the offspring
      associated with intrauterine drug exposure.

PMID- 9614426
TI  - Facilities and equipment for the care of pediatric patients in a community
      hospital. American Academy of Pediatrics Committee on Hospital Care.
AB  - Most children requiring hospitalization are admitted to community hospitals that
      vary significantly in their pediatric resources. The intent of this statement is
      to provide guidelines for furnishing and equipping a pediatric area in a
      community hospital.

PMID- 9614427
TI  - The role of the pediatrician in recognizing and intervening on behalf of abused
      women. American Academy of Pediatrics Committee on Child Abuse and Neglect.
AB  - Pediatricians are in a position to recognize abused women in pediatric settings.
      Intervening on behalf of battered women is an active form of child abuse
      prevention. Knowledge of local resources and state laws for reporting abuse are
      emphasized.

PMID- 9614428
TI  - Retinopathy of prematurity guidelines.

PMID- 9614429
TI  - Inhaled nitric oxide prevents severe hypoxemia in newborns with acute lung
      disease and pulmonary hypertension.

PMID- 9614430
TI  - Scalding, dust mites and lice, and your washing machine.

PMID- 9614431
TI  - Babywalker-related injuries continue despite warning labels and public education.

PMID- 9614432
TI  - Neonatal viability: pushing the envelope.

PMID- 9614433
TI  - What's CIPRO?

PMID- 9614434
TI  - Cover illustration: case of the month: early invasive rectal cancer.

PMID- 9614435
TI  - Pharmacokinetics of cisplatin and combination chemotherapy of cisplatin plus 5
      FU.

PMID- 9614436
TI  - Japan Clinical Oncology Group (JCOG).
AB  - The Japan Clinical Oncology Group (JCOG) is a cooperative oncology group with the
      aims of conducting, developing, coordinating and stimulating clinical research in
      Japan on the treatment of cancer and related problems. The purpose of JCOG is to
      establish and improve the standard of cancer treatment, mainly in solid cancer,
      through the testing of new therapeutic regimens or combined modalities, using
      drugs that are newly-approved or already commercially available. Research
      sponsored by JCOG is accomplished mainly through the execution of large,
      prospective, randomized, multicenter, clinical trials. In this way, JCOG
      facilitates the passage of new clinical trial discoveries into state-of-the-art
      treatment.

PMID- 9614437
TI  - Experimental chemical carcinogenesis in the stomach and colon.
AB  - Experimental chemical carcinogenesis in the digestive tract is reviewed, mainly
      on the basis of information obtained in the laboratories of the National Cancer
      Center Research Institute. It is generally accepted that cancer is the outcome of
      DNA damage, resulting in mutation, loss, amplification and recombination of
      genes. Gastric cancer is no exception. It was shown very early that cancer of the
      glandular stomach can be produced in rats by administration of N-methyl-N'-nitro
      N-nitrosoguanidine (MNNG), a widely used mutagen. However, this depends on the
      genotype. Whereas the ACI rat is susceptible to MNNG, the Buffalo rat is
      resistant and this is a dominantly inherited trait. Genes responsible for the
      sensitivity to gastric cancer induction are at present under investigation by
      linkage analysis of rat genome markers. With regard to cancer in humans, our
      finding that cooked proteinaceous foods can give rise to a series of heterocyclic
      amines (HCAs) is of major significance. 2-Amino-1-methyl-6-phenylimidazo[4,5
      b]pyridine (PhIP), one of the most abundant, causes colon cancers in male rats,
      whereas in females it induces breast cancers. The colon cancers induced by PhIP
      feature a deletion of G as represented by 5-GGGA-3-->5-GGA-3 in the Apc gene,
      resulting in a truncated Apc molecule. Microsatellite mutations have also been
      found in PhIP-induced colon tumors, as in human hereditary non-polyposis
      colorectal cancer cases. Similarly to the case of gastric cancer production by
      MNNG, there is a genetic component and F344 rats are more susceptible to PhIP
      colon carcinogenesis than the ACI/N strain and the gene responsible is being
      sought. Since carcinogenesis proceeds with accumulation of genetic alteration,
      often involving genomic instability, exposure to any kind of carcinogenic
      substances, either xeno- or autobiotics, needs to be reduced as far as possible,
      taking account of inconvenience at the individual and socio-economical levels.

PMID- 9614438
TI  - Pharmacokinetics of cisplatin in combined cisplatin and 5-fluorouracil therapy: a
      comparative study of three different schedules of cisplatin administration.
AB  - BACKGROUND: Cisplatin is widely used in combination chemotherapy against a
      variety of tumors; however, the optimal administration schedule of cisplatin is
      still controversial. To clarify the pharmacokinetic differences according to the
      administration schedules of cisplatin, we compared three different administration
      schedules of cisplatin such as single short-term infusion, daily short-term
      infusion and daily continuous infusion in combination with 5-fluorouracil.
      Preliminary clinical responses and toxicities were also investigated. METHODS: A
      total of 12 courses in combination of cisplatin and 5-fluorouracil therapy was
      studied. The schedules of cisplatin tested were as follows: single short-term
      infusion (80 mg/m2, day 1,2 h div., n = 4), daily short-term infusion (20 mg/m2,
      days 1 to 5, 2 h div., n = 4), daily continuous infusion (100 mg/m2, 120 h, n =
      4). In all schedules, 5-fluorouracil was continuously administered at a dose of
      800 mg/m2/day on days 1 to 5. The area under the time-concentration curve (AUC)
      and the maximum concentration (Cmax) of total and free Pt were investigated.
      RESULTS: The highest AUC of total and free Pt and the lowest Cmax of free Pt were
      observed in the daily continuous infusion (total AUC; 162.53 +/- 18.39 micrograms
      h/ml, free AUC; 5.50 +/- 0.9 micrograms h/ml, free Cmax; 0.07 +/- 0.01
      microgram/ml, mean +/- SEM). Two patients in the single short-term infusion and
      one patient in the daily continuous infusion indicated partial responses
      clinically. No nephrotoxicity or ototoxicity was observed. All toxicities were
      mild and tolerable in all regimens; however, the incidence of GI toxicity in
      daily continuous infusion seemed to be relatively higher. CONCLUSIONS: Daily
      continuous infusion of cisplatin gave the best pharmacokinetic results and to
      evaluate the clinical advantage of this schedule a prospective randomized trial
      should be conducted with sufficient numbers of patients.

PMID- 9614440
TI  - Changes in levels of serum erythropoietin, serum iron and unsaturated iron
      binding capacity during chemotherapy for lung cancer.
AB  - BACKGROUND: The serum erythropoietin level increases markedly during chemotherapy
      for leukemia. A number of hypotheses have been built for the mechanism, none of
      them satisfactory. Difficulty in evaluating bone marrow activity hampers the
      elucidation. Therefore, we focused on patients who had non-hematological cancer
      and no evidence of bone marrow suppression. METHODS: Twelve patients, who had
      lung cancer (four with small cell cancer and eight with non-small cell cancer)
      and who had not undergone any chemotherapy, were studied. During chemotherapy, we
      measured serum erythropoietin, serum iron, unsaturated iron binding capacity and
      hemoglobin concentration in these patients. RESULTS: The serum erythropoietin
      level before chemotherapy (10.8 +/- 7.4 mU/ml) was within the normal range but
      the peak values after the first treatment (73.4 +/- 90.4 mU/ml) increased in all
      patients. In the patients with small cell cancer, a transient but marked increase
      in erythropoietin value (204.6 +/- 167.3 mU/ml) was observed after each session
      of chemotherapy while hemoglobin concentration decreased gradually. Throughout
      treatments, elevation of the serum iron concentration and concomitant reduction
      of unsaturated iron binding capacity were observed after each session of
      chemotherapy. They regained their original values whilst the serum erythropoietin
      level decreased after each chemotherapy session was completed. CONCLUSIONS: It is
      suggested that the suppression of erythroid marrow by chemotherapeutic agents
      causes the changes in serum erythropoietin level during chemotherapy in patients
      with lung cancer.

PMID- 9614439
TI  - Frequent expression of the vascular endothelial growth factor in human non-small
      cell lung cancers.
AB  - BACKGROUND: Angiogenesis is an essential factor for progression and metastases in
      solid tumors. It has been reported that several angiogenic factors play a role in
      the regulation of angiogenesis. Vascular endothelial growth factor (VEGF) is one
      of the most important molecules in angiogenesis. We investigated expressions of
      VEGF in a series of lung carcinomas with regard to clinicopathological factors.
      METHOD: VEGF expression was investigated by use of immunohistochemical studies
      and Northern blot analysis, using 155 primary and 26 metastatic lung carcinomas
      for the immunohistochemical studies and 10 primary and two metastatic lung
      carcinomas for the Northern blot analysis. All lesions were resected at surgery.
      RESULTS: The frequencies for positive VEGF expression were 64 of 74 (86.5%)
      adenocarcinomas, 38 of 67 (56.7%) squamous cell carcinomas, four of four (100%)
      large cell carcinomas, two of three (66.7%) adenosquamous carcinomas and one of
      five (20%) small-cell carcinomas, the degree of positivity generally being
      greater in well differentiated tumors. The majority of metastatic foci from
      adenocarcinomas and squamous cell carcinomas at other sites were also positive
      (76.5 and 66.7%, respectively). VEGF expression did not correlate with
      clinicopathological factors such as tumor size or pathological stage, but
      pathological stage I adenocarcinoma cases positive for VEGF demonstrated a
      shorter disease-free period when followed up for 48 months than those cases
      expressing VEGF negatively. CONCLUSIONS: The results indicated that VEGF
      expression was frequently detected in non-small-cell lung cancers and suggested
      that VEGF might relate to the disease-free period of the patients with early
      adenocarcinomas.

PMID- 9614441
TI  - Ultrasound-guided small-bore Elecath tube insertion for the rapid sclerotherapy
      of malignant pleural effusion.
AB  - BACKGROUND: Traditional pleurodesis for malignant pleural effusion is performed
      by large-bore chest tube insertion with the instillation of sclerosing agents
      after the compressed lung re-expansion and pleural fluid drainage of 100-150
      ml/day. This study was carried out to evaluate the possibility of rapid
      sclerotherapy for malignant pleural effusions by insertion of a small-bore
      Elecath tube (12-French) under ultrasound guidance and intrapleural injection of
      bleomycin 60 IU. METHODS: Twenty-six patients, with 28 cytopathologically proven
      malignant pleural effusions (two patients had bilateral pleural effusions) and
      receiving the insertion of the Elecath tube for drainage, were included in our
      series. This rapid and short-term sclerosing method was performed and completed
      by intrapleural injection of bleomycin when the pleural effusion had been clearly
      drained by the small-bore Elecath tube and the compressed lung had fully re
      expanded on follow-up chest radiographs. RESULTS: Twenty patients with 22 pleural
      effusions underwent the intrapleural injection of bleomycin, with the results of
      pleurodesis being complete response 41% (9/22), partial response 36% (8/22) and
      failure 23% (5/22). Interestingly, among the 17 successful procedures of
      pleurodesis (complete response and partial response), 71% (12) procedures could
      be completed within 2 days (seven within one day and five within 2 days). The
      remaining unsuccessful procedures carried out on six patients without the
      injection of bleomycin were due to a non-re-expanded lung (n = 3) and inadequate
      drainage (n = 3); of these, four patients also received the large-bore chest tube
      insertion after the removal of the Elecath tube, but the compressed lung still
      could not re-expand. The complications of the bleomycin injection were fever [77%
      (17/22)], vomiting [14% (3/22)] and hiccup [5% (1/22)]. CONCLUSION: The method of
      rapid sclerotherapy for malignant pleural effusions by small-bore Elecath tube is
      promising, with a success rate achieving 77%, usually within 2 days.

PMID- 9614442
TI  - Identification and characterization of families with aggregation of lung cancer.
AB  - BACKGROUND: To clarify genetic factors involved in the susceptibility to lung
      cancer, it is essential to identify families with lung cancer clustering and to
      characterize the mode of clustering. Since somatic mutations of the p53, RB and
      p16 genes occur frequently in lung cancer and the replication error phenotype is
      seen in a subset of lung cancer, it is possible that germ-line mutations of the
      p53, RB, p16 and mismatch repair genes influence the susceptibility to lung
      cancer. METHODS: In this work, cases with familial clustering of lung cancer were
      selected from 1068 families with primary lung cancer cases in analogy with the
      criteria for hereditary non-polyposis colorectal cancer (HNPCC). Cases with Li
      Fraumeni syndrome, familial retinoblastoma, familial melanoma and HNPCC were also
      searched among these 1068 families. RESULTS: There were only four families (0.4%)
      in which more than three relatives were affected by lung cancer. Two successive
      generations were affected in 36 families (3.4%). Patients with lung cancer before
      the age of 50 were present in 165 families (15.5%). However, no family conformed
      to all three criteria. There was only one family with Li-Fraumeni syndrome and no
      family with familial retinoblastoma, familial melanoma and HNPCC. CONCLUSION:
      Familial aggregation of lung cancer is rare and germ-line mutations of the p53,
      RB, p16 and mismatch repair genes may not contribute greatly to susceptibility to
      lung cancer.

PMID- 9614443
TI  - Growth patterns and genetic changes of colorectal carcinoma.
AB  - BACKGROUND: Recent Japanese studies have shown that histogenesis of small
      colorectal carcinomas can be divided into two groups: polypoid growth arising
      from polypoid neoplasia, and nonpolypoid growth arising from flat or depressed
      neoplasia. This classification should be verified with genetic as well as
      morphologic characteristics. SUBJECTS AND METHODS: In order to classify our
      subject into polypoid growth and nonpolypoid growth types both histologically and
      endoscopically, we selected 42 colorectal carcinomas < 2 cm in size (35
      submucosal and seven more advanced). Clinicopathological findings, presence or
      absence of Ki-ras gene mutation and overexpression of p53 protein were compared
      between the two types. RESULTS: Histologically, the cases were divided into 27 of
      the polypoid growth type and 15 of the nonpolypoid growth type. None of the
      nonpolypoid growth cases contained adenomatous remnant, wheras this was found in
      75% of the polypoid growth cases. No Ki-ras mutation was observed in any of the
      nonpolypoid growth cases, although it appeared in 44% of the polypoid growth
      cases. Regarding the overexpression of p53 protein, no significant difference was
      observed between the two types. The histological and the colonoscopic polypoid
      growth-nonpolypoid growth classifications correlated well with each other
      (agreement rate 98%), except for one lesion, which was classified as polypoid
      growth type endoscopically but as nonpolypoid growth type histologically.
      CONCLUSIONS: The histologically defined polypoid growth-nonpolypoid growth
      classification may indicate a difference in pathway of colorectal carcinogenesis.
      Also, colonoscopic polypoid growth-nonpolypoid growth classification is available
      for preoperative estimation of the genetic characteristics of small carcinomas.

PMID- 9614444
TI  - Characteristics in primary signet-ring cell carcinoma of the colorectum, from
      clinicopathological observations.
AB  - BACKGROUND: The biological behavior of signet-ring cell carcinomas in colorectum
      tends to be worse than that of mucinous carcinomas. However, in previous studies,
      clinicopathological features of this disease have been somewhat ill-defined
      because various histological criteria of this disease were adopted. METHODS: We
      selected 11 cases of signet-ring cell carcinomas and 29 cases of mucinous
      carcinomas among 1595 consecutive colorectal carcinomas on defined criteria and
      compared clinicopathological and molecular biological features between these two
      types of carcinomas. RESULTS: Clinical staging of signet-ring cell carcinomas
      were far advanced and their prognosis tended to be worse than that of mucinous
      carcinomas. Furthermore, the incidence of K-ras mutations in signet-ring cell and
      mucinous carcinomas showed no difference between these two types of carcinomas.
      However, the incidence of K-ras mutation in these diseases was slightly lower
      than that in 30 ordinary colorectal carcinomas examined as a comparison.
      CONCLUSIONS: These results suggest that the carcinogenesis of signet-ring cell
      and mucinous carcinomas are different from that of ordinary colorectal carcinomas
      and that there may exist other genes related to malignancy of signet-ring cell
      carcinomas.

PMID- 9614445
TI  - Early stage nasopharyngeal carcinoma: radiotherapy dose and time factors in tumor
      control.
AB  - OBJECTIVE: To evaluate radiotherapy dose and length of treatment in the control
      of early stage nasopharyngeal carcinoma (NPC) treated with a combination of
      external radiotherapy and brachytherapy, MATERIALS & METHODS: We reviewed the
      records of 133 patients with early stage nasopharyngeal carcinoma (stage I or II,
      AJC/UICC staging system) who received definitive radiotherapy in Chang Gung
      Memorial Hospital from 1979 to 1991. The median follow-up time was 7.1 years with
      a minimum of 2 years. All patients were treated with megavoltage external
      radiotherapy to the nasopharynx area (63-72 Gy) followed by high dose rate
      intracavitary brachytherapy (5-16.5 Gy in one to three fractions, spaced 1-2
      weeks apart). The median total dose and time of irradiation was 75 Gy (69.8-81.4
      Gy) and 11.6 weeks (7.8-20 weeks) respectively. Survival analysis was used to
      examine the effect of several variables on prognosis. RESULTS: The 5-year rates
      were 86.4% for local control, 84.7% for disease free survival, 88.5% for
      actuarial survival and 84.2% for overall survival. The treatment group
      (combination of time and dose of irradiation) was the most important prognostic
      factor according to Cox's proportional hazard model. Patients receiving radiation
      at a total dose of < or = 75 Gy completed in < 12 weeks showed the best
      prognosis. CONCLUSION: Treatment time and total treatment dose are both important
      factors in treating early stage NPC. Decreasing the total radiation time to < 12
      weeks and not exceeding a radiation dose of 75 Gy gave the best results.

PMID- 9614446
TI  - Factors that influence the eligibility of cases for inclusion in clinical trials.
      The Lung Cancer Chemotherapy Study Group of the Japan Clinical Oncology Group.
AB  - BACKGROUND: It is important to minimize the incidence of ineligible cases to
      improve the quality of clinical trials. To determine factors which may influence
      the incidence of ineligible cases, the incidence of and reasons for ineligibility
      in clinical trials were retrospectively analyzed. METHODS: We retrospectively
      examined the incidence of and reasons for ineligibility for inclusion in eight
      clinical trials conducted by the Lung Cancer Chemotherapy Study Group of the
      Japan Clinical Oncology Group and four trials financed by trust funds from a
      pharmaceutical company. RESULTS: In these 12 clinical studies, the incidence of
      ineligibility was 4.2% (32/762) (range 0-10.6%). Specific factors that might
      influence the incidence of ineligible cases were then analyzed. There was a
      significant difference in the incidence of ineligibility between the methods of
      registration (P < 0.05). The incidences using a central registration and without
      using a central registration system were 2.8% (9/322) and 5.2% (23/440)
      respectively. We also analyzed ineligible cases in clinical studies published in
      the Journal of Clinical Oncology. In clinical studies published in the Journal of
      Clinical Oncology recently and 10 years ago, the incidences of ineligible cases
      were 5.0% (942/18 878) and 4.1% (206/4995) respectively. In clinical studies on
      lung cancer published in the Journal of Clinical Oncology from 1984 to 1995, the
      incidence of ineligible cases was 4.7% (900/19,116). There was no significant
      difference in the incidence of ineligible cases between our 12 studies and the
      Journal of Clinical Oncology clinical studies by the chi 2 test (P > 0.05).
      CONCLUSIONS: We conclude that the incidence of ineligible cases in our studies is
      similar to that in clinical trials published in the Journal of Clinical Oncology.
      Central registration systems are useful for checking for ineligibility, and to
      increase the quality of clinical trials.

PMID- 9614447
TI  - Rhabdomyosarcoma of the diaphragm: report of an adult case.
AB  - Diaphragmatic tumors, whether benign or malignant, may not generally reveal any
      symptoms in the early phase and may be found accidentally. During a pre
      employment physical examination, a 20-year-old woman was found to have an
      abnormal shadow on the left diaphragm. An X-ray film, computed tomography and
      ultrasonography showed a giant mass on the left side, to the rear of the heart.
      She underwent surgery via a left thoraco-abdominal approach. The lesion was found
      to arise from the left diaphragm, and multiple disseminated lesions were
      scattered in the left thoracic cavity. Histological examination showed many
      large, oxyphilic rhabdoid cells between diffusely proliferating, spindle-shaped
      cells, and the tumor was subsequently diagnosed as a pleomorphic rhabdomyosarcoma
      of the diaphragm, of which the location and histological type were very rare.
      Despite adjuvant therapy, chest X-ray and CT revealed increasing tumor growth in
      the left cavity and she died one year after surgery.

PMID- 9614448
TI  - Assessment of cell cycle-related elements p53, p21WAF1/Cip1, cyclin D1 and PCNA
      in a mixed transitional cell carcinoma and adenocarcinoma of the renal pelvis: a
      case report.
AB  - A case featuring a well differentiated adenocarcinoma mixed with a transitional
      cell carcinoma (TCC) arising in the renal pelvis of a 63-year-old woman is
      presented. Daughter tumors, located in the ureter and the uretero-vesical
      junction, were entirely TCC in character. Immunohistochemical assessment of cell
      cycle-related proteins revealed overexpression of cyclin D1 but reduced
      p21WAF1/Cip1 or PCNA expression in the adenocarcinomatous regions. Conversely,
      expression of p21WAF1/Cip1 and PCNA was high in the TCC components.
      Immunohistochemical staining for p53 was negative and PCR-SSCP analyses confirmed
      the absence of any mutation. Therefore, assessments on the altered expression of
      cell cycle-related elements may contribute to our understanding of tumor biology
      in adenocarcinomas and TCCs of the renal pelvis and to identifying the
      similarities and differences between the two different cell types.

PMID- 9614449
TI  - Mapping malaria transmission intensity using geographical information systems
      (GIS): an example from Kenya.
AB  - That there are so few examples of the use of epidemiological maps in malaria
      control may be explained by the lack of suitable, spatially defined data and of
      an understanding of how epidemiological variables relate to disease outcome.
      However, recent evidence suggests that the clinical outcomes of infection are
      determined by the intensity of parasite exposure, and developments in
      geographical information systems (GIS) provide new ways to represent
      epidemiological data spatially. In the present study, parasitological data from
      682 cross-sectional surveys conducted in Kenya were abstracted and spatially
      defined. Risks of infection with Plasmodium falciparum among Kenyan children,
      estimated from combinations of parasitological, geographical, demographic and
      climatic data in a GIS platform, appear to be low for 2.9 million, stable but low
      for another 1.3 million, moderate for 3.0 million and high for 0.8 million.
      (Estimates were not available for 1.4 million children.) Whilst the
      parasitological data were obtained from a variety of sources across different age
      groups and times, these markers of endemicity remained relatively stable within
      the broad definitions of high, moderate and low transmission intensity. Models
      relating ecological and climatic features to malaria intensity and improvements
      in our understanding of the relationships between parasite exposure and disease
      outcome will hopefully provide a more rational basis for malaria control in the
      near future.

PMID- 9614450
TI  - Detection in human sera of IgG, IgM and IgA to excreted/secreted antigens from
      Toxoplasma gondii by use of dot-ELISA and immunoblot assay.
AB  - The excreted/secreted antigens (ESA) of Toxoplasma gondii are thought to play an
      important role in the pathogenesis and immune escape of the parasite and the
      host's immunity to infection with it. In the present study, ESA from peritoneal
      exudates of infected mice were precipitated with ammonium sulphate (a 40%
      saturated solution giving the best yield of antigenic components). They were then
      analysed by immunoblot assay and dot-ELISA using serum samples from 25 patients
      with toxoplasmosis (19 in the acute phase and six chronic). Three groups of
      antigens, with molecular masses of 35, 30-32 and 26 kDa, reacted strongly with
      IgG antibodies, and antigens from two of these groups (30-32 and 26 kDa) also
      reacted with IgM and IgA.

PMID- 9614451
TI  - Plasma concentrations of artemether and its major plasma metabolite,
      dihydroartemisinin, following a 5-day regimen of oral artemether, in patients
      with uncomplicated falciparum malaria.
AB  - Plasma concentrations of artemether and its active plasma metabolite
      (dihydroartemisinin) were measured in 49 male, Thai patients with acute,
      uncomplicated, multidrug-resistant, Plasmodium falciparum malaria, following
      their treatment with oral artemether (300 mg on the first day, then 100 mg daily
      for another 4 days). Four patients recrudesced (on days 19-22). After the first
      dose, artemether became undetectable in < or = 18 h and this drug was also
      undetectable in samples collected immediately before each dose. Although
      dihydroartemisinin followed similar trends, three patients had detectable plasma
      concentrations of this metabolite 24 h after the first dose (i.e. immediately
      before the second dose). Median (range) values for plasma concentrations of
      dihydroartemisinin 6 h [354 (150-751) v. 196 (178-220) ng/ml] and 12 h [158 (25
      420) v. 54 (25-115) ng/ml] after the initial dose, estimated antimalarial
      activities (calculated as dihydroartemisinin equivalents) 6 h [331 (78.2-644.1)
      v. 23 (183.3-270) nmol/litre] and 12 h [98.3 (10-192.2) v. 56.7 (9.8-59.4)
      nmol/litre] after the initial dose, and the corresponding 'areas under the
      curves' (AUC) [3684 (1562-8216) v. 834 (1401-2030) ng.h/ml] were all
      significantly higher in the patients with sensitive responses than in those who
      recrudesced.

PMID- 9614453
TI  - Rosetting characteristics of uninfected erythrocytes from healthy individuals and
      malaria patients.
AB  - Rosetting, defined as the binding of two or more uninfected red blood cells (rbc)
      to an infected rbc, occurs when malarial parasites mature, to trophozoites and
      schizonts, in the second half of their asexual development. Rosetting is believed
      to be an important factor in the development of cerebral malaria. In a series of
      studies to examine the characteristics of the uninfected rbc which contribute to
      rosetting, the ability of rbc from healthy donors to form rosettes was found to
      be greater in the cells of group A and B than in those of group O (P = 0.05), and
      to decrease during storage under blood-blank conditions. Normal rbc exposed for >
      or = 30 min to quinine, artesunate or artemether (each at 0.25 microgram/ml) in
      vitro showed significantly decreased rosetting. This effect could not be reversed
      by extensive washing followed by cultivation for another 24 h in drug-free
      medium. Mefloquine and pyrimethamine had no effect. Uninfected rbc from patients
      with uncomplicated or severe falciparum malaria exhibited a lower rosetting
      ability than rbc from healthy donors (P = 0.01). The rosetting of uninfected rbc
      of all blood groups from patients with uncomplicated malaria decreased
      significantly within 2 h of the patients starting treatment with qinghaosu
      derivatives (artesunate or artemether) and within 8 h of them starting quinine
      treatment. Similar effects were observed with uninfected rbc from patients with
      severe malaria after treatment with artesunate but not after quinine. The
      mechanisms underlying this potentially beneficial effect on rbc adherence are not
      known.

PMID- 9614452
TI  - Effect of chloroquine prophylaxis during pregnancy on maternal haematocrit.
AB  - Two controlled trials of chloroquine prophylaxis during pregnancy were performed,
      one in Burkina Faso in 1987, on all pregnant women, and the other in Cameroon in
      1992, on primigravidae only. Maternal haematocrit at delivery was found to be
      significantly higher in those women who had received chloroquine than in those
      who had not, both in Burkina Faso (37.4% v. 36.5%; P = 0.01) and in Cameroon
      (34.8% v. 32.8%; P = 0.02). Anaemia, defined as an haematocrit of < 30%, was also
      less common in those treated with chloroquine (6.3% v. 8.5% in Burkina Faso and
      8.3% v. 18.4% in Cameroon) but this difference was not significant in either
      country. A slight improvement in haematological status when prophylaxis is given
      has also been observed in similar studies performed in other tropical countries.
      The present results confirm the usefulness of targeting antimalarial prophylaxis
      at pregnant women. Such prophylaxis during the first pregnancy also increases
      birthweight.

PMID- 9614454
TI  - Susceptibility to Leishmania major of different populations of Phlebotomus
      papatasi (Diptera: Psychodidae) from endemic and non-endemic regions of Egypt.
AB  - The ability of three populations of Phlebotomus papatasi collected from different
      areas of Egypt (Sinai, Aswan and Delta regions) to acquire successfully and
      transmit Leishmania major (Sinai sandfly isolate IPAP/EG/89/SI-177) was evaluated
      in the laboratory. Flies from each population were fed artificially on infected
      blood suspensions, using a chick-skin-membrane feeding apparatus, and naturally
      on infected mice. Samples of fed flies were dissected and examined
      microscopically to determine the infection rate and intensity of parasite
      infection. The Aswan population had a significantly lower feeding rate (16.2%)
      than the Sinai (51.2%) and Delta (69.7%) populations (P < 0.0001). The infection
      rate for the Sinai population was significantly higher (65.9%) than the rate for
      the Delta (52.3%; P < 0.05) and slightly higher than that for the Aswan (62.5%).
      No differences were observed in the intensity of L. major infection in the
      midguts of the sandflies examined from any of the three populations. When flies
      from each population were fed naturally on BALB/c mice infected with L. major,
      the feeding rates of the three populations showed a similar pattern to that seen
      in the membrane feeds, with the Aswan population having the lowest rate. In each
      of two separate trials for each population, a group of artificially infected
      flies was refed on uninfected BALB/c mice. Thirty-six days following exposure to
      the infected sandflies in the Sinai population, a leishmanial lesion was observed
      on the corner of one animal's mouth. These observations provide the final piece
      of evidence that P. papatasi is a vector of L. major in Egypt.

PMID- 9614455
TI  - Experimental control of the schistosome-transmitting snail Biomphalaria pfeifferi
      by the ampullariid snail Pila ovata.
AB  - Adults of the African ampullariid snail Pila ovata were examined for their
      ability to control laboratory populations of the pulmonate snail Biomphalaria
      pfeifferi, a widespread, intermediate host of the human pathogen Schistosoma
      mansoni in sub-Saharan Africa. In a 6-week experiment conducted in large (100 x
      60 x 60 cm) outdoor tanks containing floating macrophytes (Nymphaea caerula) and
      initially set up with one adult ampullariid for every three adult pulmonates, the
      numbers of B. pfeifferi egg masses were always about half those in similar tanks
      without P. ovata. Although, by week 6, the numbers of B. pfeifferi in the control
      tanks (without ampullariids) had increased 5-fold, from an initial mean of 30
      snails/tank, there was no significant increase in the numbers of B. pfeifferi in
      the experimental tanks (containing ampullariids). Results of experiments
      conducted in indoor glass aquaria indicated that adult P. ovata rapidly attacked
      egg masses or neonates (< 2.5 mm shell diameter) of B. pfeifferi but had no
      effect on the adults. The adult ampullariids also significantly decreased cover
      by floating macrophytes over a 6-week period compared with that in similar but
      ampullariid-free aquaria. This decrease in plant cover is relevant to biological
      control of the schistosome vectors as macrophytes serve as food, shelter and
      oviposition sites for pulmonate snails. The present result indicate the ability
      of P. ovata to inhibit multiplication of B. pfeifferi populations, at least under
      laboratory conditions, both directly, through predation, and indirectly, by
      competition for resources. Pila ovata may therefore prove useful in the
      biological control of medically important, pulmonate snails.

PMID- 9614456
TI  - Comparison of a whole-blood agglutination test and an ELISA for the detection of
      the antigens of Dirofilaria immitis in dogs.
AB  - To compare the usefulness of two commercial tests for detecting the antigens of
      Dirofilaria immitis in dogs, one based on whole-blood agglutination (WBA) and the
      other on ELISA, 100 stray dogs from North Taiwan were tested before necropsy. Of
      the 53 dogs found to contain D. immitis at necropsy, which had a mean (S.D.)
      burden of 8.2 (10.6) worms/dog, 45 were found to be positive by WBA and 47 by
      ELISA. All the false negatives were dogs with very low worm burdens. Although the
      ELISA was more sensitive (83.9% v. 71.7%) and specific (100% v. 85.1%) than the
      WBA, the latter is simpler to use and less time-consuming. In terms of their
      general use for diagnosis of canine heartworm, there seems little to choose
      between the two tests. The false negatives observed with both tests are not
      likely to be a problem as they represent dogs with worm burdens which are
      probably too low to cause significant clinical manifestations or pathology. As
      the positive predictive value of the WBA test declines dramatically with
      prevalence of infection, this test may not be suitable for detecting D. immitis
      in canine populations in which heartworm infection is rare.

PMID- 9614457
TI  - Parasitic infections in villagers from three districts of the Brazilian Amazon.
AB  - A survey of intestinal parasites among 827 rural villagers in the Brazilian
      Amazon revealed that the prevalences of infection with Necator americanus,
      Trichuris trichiura and/or Ascaris lumbricoides were high. However, the
      intensities of infection with the two parasites for which there were enough data
      on intensity for further analysis, N. americanus and T. trichiura, were only low
      or moderate in each of the three districts studied. Possible reasons for the
      unusual (but not unique) absence of high intensities include moderately good
      sanitation, low population densities, the way in which work activities are
      located geographically, the use of indigenous anthelmintics and the geographical
      isolation of the communities which provided the subjects. Whether the light to
      moderate levels of infection observed require intervention is discussed.

PMID- 9614458
TI  - Prevalence of infection with hepatitis G virus among various groups in Thailand.
AB  - Two research groups recently and independently, isolated a hepatotropic
      flavivirus from human sera. The two viruses, named GB virus C and hepatitis G
      virus (HGV), were subsequently discovered to represent the same virus, which was
      associated with acute and chronic hepatitis of the non-A-E type. The prevalences
      of infection with HGV have now been investigated in various groups of the Thai
      population, some of which [e.g. thalassaemic children, patients with chronic
      liver disease, carriers of antibodies to hepatitis B virus and/or hepatitis C
      virus (HCV), prostitutes and intravenous-drug users (IVDU)] were assumed to be at
      high risk. Samples of sera were investigated by reverse-transcriptase PCR, using
      four primers created from the 5' untranslated region of HGV. The prevalence of
      HGV infection among the healthy controls (1%-5%) was found to be much less than
      that among thalassaemic children (32.6%), asymptomatic carriers of anti-HCV
      (20.4%), IVDU (18.2%), aplastic anaemia patients (14.3%) and prostitutes (10%),
      although similar to that in patients with chronic liver disorders. These results
      confirm a parenteral route of transmission for HGV and emphasise the need for
      further research to determine the clinical significance of this virus.

PMID- 9614459
TI  - Characterization of a virus isolated from the cerebrospinal fluid of patients
      with epidemic neuropathy.
AB  - A previously unknown disease, termed epidemic neuropathy (EN), occurred in Cuba
      between 1991 and 1993. When samples of cerebrospinal fluid (CSF) from 45 patients
      with EN and 11 controls were inoculated into cultures of VERO cells, almost all
      (93%) of the samples from the cases of EN but only one (9%) of the control
      samples produced a slowly progressing cytopathological effect (CPE). Although the
      results of other studies indicated the presence of a picornavirus-like virus in
      CSF samples from EN cases, the CPE and other physico-chemical characteristics
      observed were not those expected of picorn-viruses. Several aetiological factors
      may have contributed to EN but at least one virus could have played a major role.

PMID- 9614460
TI  - Tungiasis among five communities in south-western Trinidad, West Indies.
AB  - The prevalences of Tunga penetrans Linn. within the five townships of Granville,
      Fullerton, Icacos, Coromandel and Cedros in south-western Trinidad, West Indies,
      as determined by physical examination of all inhabitants present during the
      survey, were 17.0% (38/223 subjects), 15.7% (36/237), 31.4% (102/325), 17.4%
      (42/242) and 17.9% (50/280), respectively. The rate in Icacos was significantly
      higher than in the other four sites (P < 0.001). Not only were males more likely
      to be infected than females in all five study sites (P < 0.0007) but chigoe-flea
      burdens were also higher in males than in females (P < 0.012), with mean (S.D.)
      burdens of 5.44 (2.54) fleas/male infected subject and 2.38 (2.00) fleas/female
      infected subject. Feet were significantly more infected than other areas of the
      body (P < 0.001). Analysis of variance revealed that the interactions between
      prevalence of chigoe-flea infection and geographical location (P = 0.0058) and
      between sex of infected subject and site of infection (P = 0.0109) were highly
      significant but that between geographical location and sex of infected subject
      was not significant (P > 0.30). At least seven species of bacteria, with varying
      sensitivities to antibiotics, were isolated from 16 patients with sepsis
      associated with their T. penetrans infections: Streptococcus pyogenes, beta
      haemolytic Streptococcus (not group A), Klebsiella aerogenes, Enterobacter
      agglomerans, Staphylococcus aureus, Escherichia coli and a Bacillus species.
      Closteridium tetani was not isolated.

PMID- 9614461
TI  - Kinetics and efficiency of Plasmodium falciparum development in the midguts of
      Anopheles gambiae, An. funestus and An. nili.

PMID- 9614462
TI  - Increased antibody response to parasite lipids in amicrofilaraemic individuals
      from a region where Wuchereria bancrofti infection is endemic.

PMID- 9614463
TI  - Dirofilaria immitis in Tikuna Indians and their dogs in the Colombian Amazon.

PMID- 9614464
TI  - The use of theatre to mobilize and sensitize rural communities to participate in
      tsetse control in Bugiri district, Busoga, Uganda: a case study.

PMID- 9614465
TI  - Original publications.

PMID- 9614466
TI  - Research and development in the NHS. New lamps for old.

PMID- 9614467
TI  - Qualitative research.

PMID- 9614468
TI  - Asperger syndrome and high-functioning autism.

PMID- 9614469
TI  - Questionable validity of 'dissociative amnesia' in trauma victims. Evidence from
      prospective studies.
AB  - BACKGROUND: We reviewed evidence from prospective studies to test whether
      individuals can develop amnesia for traumatic experiences, a process variously
      termed 'repression', 'dissociative amnesia' or 'psychogenic amnesia'. METHOD:
      Using specified criteria, we selected and analysed studies which prospectively
      assessed memory in victims of documented traumatic experiences. RESULTS: In
      studies in which people were asked directly about a past traumatic experience,
      they consistently reported memories. Non-reporting occurred only in studies where
      subjects were not asked directly about the experience. This latter design leaves
      open the well-documented possibility that subjects simply did not disclose events
      that they actually remembered. Some prospective studies were also limited by
      incomplete documentation of trauma and failure to rule out other more ordinary
      causes of amnesia. CONCLUSIONS: Prospective data as yet fail to demonstrate that
      individuals can develop dissociative amnesia for traumatic events.

PMID- 9614470
TI  - Mental disorder and violence. A special (high security) hospital study.
AB  - BACKGROUND: From a first clinical description of a complete resident sample of
      special (high security) hospital patients, we examined the association between
      mental disorder and violence. METHOD: A record survey of all 1740 patients
      resident at any time between 1 January and 30 June 1993, inclusive, and, for
      most, the official criminal record. RESULTS: 1015 patients (58%) had functional
      psychosis, one-quarter of whom also had an independent personality disorder; 461
      (26%) had personality disorders uncomplicated by psychosis, and 264 (16%) had
      learning disabilities. Pre-admission substance misuse, which was probably under
      recorded, had been most common among those with psychosis and an independent
      personality disorder. Less than 10% had never been convicted of a criminal
      offence, although 25% had been admitted directly from other hospitals. Direct
      personal violence was more common among men, and fire-setting among women.
      Schizophrenia was most strongly associated with personal violence. More than 75%
      of those with a psychosis were recorded as being driven to offend by their
      delusions. In the absence of delusions, hallucinations had no such effect.
      CONCLUSIONS: For people with personality disorder better clinical descriptions
      seem essential. For people with a pure psychosis, as symptoms were usually a
      factor driving the index offence, treatment appears as important for public
      safety as for personal health.

PMID- 9614471
TI  - Meta-analysis of trials comparing antidepressants with active placebos.
AB  - BACKGROUND: Unblinding effects may introduce bias into clinical trials. The use
      of active placebos to mimic side-effects of medication may therefore produce more
      rigorous evidence on the efficacy of antidepressants. METHOD: Trials comparing
      antidepressants with active placebos were located. A standard measure of effect
      was calculated for each trial and weighted pooled estimates obtained.
      Heterogeneity was examined and sensitivity analyses performed. A subgroup
      analysis of in-patient and out-patient trials was conducted. RESULTS: Only two of
      the nine studies examined produced effect sizes which showed a consistent
      significant difference in favour of the active drug. Combining all studies
      produced pooled effect size estimates of between 0.41 (0.27-0.56) and 0.46 (0.31
      0.60) with high heterogeneity due to one strongly positive trial. Sensitivity
      analyses excluding this and one other trial reduced the pooled effect to between
      0.21 (0.03-0.38) and 0.27 (0.10-0.45). CONCLUSIONS: Meta-analysis is very
      sensitive to decisions about exclusions. Previous general meta-analyses have
      found combined effect sizes in the range 0.4-0.8. The more conservative estimates
      produced here suggest that unblinding effects may inflate the efficacy of
      antidepressants in trials using inert placebos.

PMID- 9614472
TI  - Epilepsy and non-organic non-affective psychosis. National epidemiologic study.
AB  - BACKGROUND: This study tests the hypothesis that epilepsy increases the risk of
      developing schizophrenia and other non-affective functional psychoses using a
      nationwide sample of people with epilepsy. METHOD: A record linkage study between
      a sample from the National Patient Register, consisting of 67,116 people with
      epilepsy, and the Danish Psychiatric Register identified all people with non
      affective psychoses with onset after the first epilepsy diagnosis. The relation
      between risk of psychiatric disorder in people with epilepsy and the general
      Danish population was estimated. RESULTS: The incidences of the spectrum of non
      organic non-affective psychosis, non-affective psychosis and schizophrenia were
      significantly increased both for men and women, even after exclusion of people
      diagnosed as suffering from a learning disability or substance misuse.
      CONCLUSION: This study supports the notion of an association between epilepsy and
      the risk of subsequent non-affective psychosis.

PMID- 9614473
TI  - Thirteen-year follow-up of deliberate self-harm, using linked data.
AB  - BACKGROUND: We describe a national cohort of individuals surviving an episode of
      deliberate self-harm (DSH). Subsequent admissions for DSH and mortality over the
      following 13 years were studied. METHOD: In 1981, 8304 individuals were
      discharged from Scottish general hospitals with a diagnosis of attempted suicide
      (E950-959). They were followed-up to the end of 1994 using the Scottish Linked
      Data Set. Mortality was compared to the Scottish population using person-years
      analysis. RESULTS: 2624 people (31.6%) were readmitted with further episodes of
      DSH. The median number of readmissions was 1, range 1-137. The observed:expected
      ratio for all-cause mortality was 2.26 (95% CI 2.13-2.26). One hundred and sixty
      eight people (2%) died from suicide, and 46 (0.6%) from undetermined causes. The
      observed:expected ratio for suicide plus undetermined deaths was 12.17 (95% CI
      10.64-13.91). Accidental deaths in men and homicide deaths in men and women were
      elevated. The pattern of deaths from other causes suggested that alcohol misuse
      was a contributory factor. CONCLUSIONS: People admitted to general hospitals in
      Scotland after attempted suicide are at high risk of readmission for further
      episodes of DSH. Long-term follow-up of such large cohorts is impractical, but
      services should review the scope for intervention in alcohol misuse following
      DSH.

PMID- 9614474
TI  - Reduced latent inhibition in people with schizophrenia: an effect of psychosis or
      of its treatment.
AB  - BACKGROUND: People with schizophrenia show impaired attention. This could result
      from reduced latent inhibition (a measure of ability to filter out irrelevant
      stimuli). Previous studies have found reduced auditory latent inhibition in
      people with acute schizophrenia: we tested whether this results from psychosis or
      from drug treatment. METHOD: We measured auditory latent inhibition in two
      studies. One compared antipsychotic-naive people with acute schizophrenia with
      patients within two weeks of starting antipsychotic treatment. The second
      compared healthy volunteers given either saline or 1.0 mg haloperidol,
      intravenously. RESULTS: Latent inhibition was absent in treated patients, but was
      clearly present in patients who were naive to antipsychotics. Latent inhibition
      was absent in volunteers given haloperidol, but was clearly present in those
      given saline. CONCLUSIONS: The reduced auditory latent inhibition seen in acute
      schizophrenia is more plausibly due to antipsychotic treatment than to the
      disorder. Unless neuropsychological models of schizophrenia incorporate evidence
      from drug-free patients and drug-treated healthy controls, they may be invalid.

PMID- 9614475
TI  - Psychiatric disorders as a factor in sick-leave due to other diagnoses. A general
      population-based study.
AB  - BACKGROUND: The aim was to analyse the role of psychiatric disorders in sick
      leave in different sick-leave diagnoses. METHOD: A stratified population-based
      sample of women (n = 292) in Goteborg were interviewed, and diagnoses were made
      according to DSM-III-R. Sick-leave data, including diagnoses, were obtained for
      two years. RESULTS: Women with psychiatric disorders had an increased number of
      sick-leave spells and sick-leave days in all the sick-leave diagnostic groups.
      The largest differences between the two groups of women were found in mental
      disorders, diseases of the locomotor system and gastro-intestinal diseases. The
      association between psychiatric disorders and sick-leave was strongest in older
      age groups. CONCLUSIONS: Unrecognised psychiatric disorders associated with an
      increased number of medical complaints and visits can be an important factor in
      the increase in sick-leave.

PMID- 9614476
TI  - Postal self-exposure treatment of recurrent nightmares. Randomised controlled
      trial.
AB  - BACKGROUND: Many nightmare sufferers do not consult a health care professional.
      Though behavior and cognitive therapy can help, they have not been tested as a
      self-treatment method at home using a manual. METHOD: One hundred and seventy
      adults with primary nightmares were randomised to four weeks' self-exposure or
      self-relaxation at home using manuals posted to them, or to a waiting-list as a
      control group for four weeks. Individuals recorded nightmare frequency and
      intensity in four-week diaries. RESULTS: At one- and six-month follow-up, the
      self-rated nightmare frequency fell more significantly in exposure subjects than
      relaxation or waiting-list subjects. The self-exposure group had the most drop
      outs but remained superior in an over-cautious intent-to-treat analysis. The
      individuals' partners confirmed the superiority of self-exposure to self
      relaxation at one- and six-month follow-up. CONCLUSIONS: Recurrent nightmare
      sufferers improved more with self-exposure manuals than with self-relaxation
      manuals or by being on a waiting-list. Self-exposure may be needed for longer
      than four weeks in order to reduce nightmare intensity as well as frequency.
      Despite a high drop-out rate, some sufferers of other conditions may benefit from
      self-treatment manuals.

PMID- 9614477
TI  - Validity of childhood disintegrative psychosis. General findings of a long-term
      follow-up study.
AB  - BACKGROUND: Empirical evidence for the validity of the diagnostic label
      disintegrative psychosis is sparse. The issue of whether it is a separate form of
      infantile autism is unresolved. METHOD: To investigate the validity of
      disintegrative psychosis as defined in ICD-9, the natural history of 13 cases
      were compared with 39 matched cases of infantile autism on various outcome
      variables. Average follow-up time was 22 (11-33) years. RESULTS: Statistically
      significant differences were found between the two groups in terms of number of
      admissions to non-psychiatric departments, occurrence of comorbid epilepsy,
      social style, and score on the Global Assessment of Functioning scale. In most
      other areas assessed there was a tendency, although statistically insignificant,
      towards a better outcome in the infantile autism comparison group. CONCLUSIONS:
      Our findings provide some support for maintaining a diagnostic category of
      disintegrative psychosis as distinct from infantile autism.

PMID- 9614478
TI  - Multivariate genetic analysis of the causes of temperance board registrations. In
      all Swedish male-male [correction of male-female]  twin pairs born 1926-1949.
AB  - BACKGROUND: The Temperance Boards in Sweden registered individuals for three
      reasons: public drunkenness, driving under the influence of alcohol and
      committing a crime in connection with alcohol. We wanted to ascertain whether
      these three forms of alcohol-related problems result from similar or different
      genetic and environmental risk factors. METHOD: We conducted a trivariate twin
      analysis of these three causes of registration in all male-male [corrected] twin
      pairs of known zygosity born in Sweden, 1926-1949 (n = 5177 twin pairs). RESULTS:
      Prevalences of registration for public drunkenness, drink-driving and alcohol
      related crime were, respectively, 9.0, 3.6 and 4.0%. The best-fitting model had
      one general genetic and one general familial-environmental factor with specific
      genetic risk factors for drink-driving and specific familial-environmental risk
      factors for alcohol-related crime. CONCLUSIONS: The three causes for alcohol
      registration in Sweden largely reflect the same genetic and environmental risk
      factors. Estimated heritabilities were similar for the three forms of
      registration. However, specific genetic risk factors exist for drink-driving and
      specific familial-environmental risk factors for alcohol-related crime. Genetic
      factors are somewhat less important and familial-environmental factors more
      important for public drunkenness than for drink-driving and alcohol related
      crime.

PMID- 9614479
TI  - Adults with Williams syndrome. Preliminary study of social, emotional and
      behavioural difficulties.
AB  - BACKGROUND: In recent years there has been an upsurge of interest in the study of
      distinctive patterns of behavioural and psychological characteristics associated
      with specific, biologically determined, intellectually disabling conditions. This
      study investigates whether such a profile can be identified in adults with
      Williams syndrome. METHOD: Parents and other care-givers were interviewed about
      the social, emotional and behavioural characteristics of 70 adults with Williams
      syndrome, aged 19 years to 39 years 9 months. RESULTS: The adults were reported
      to have high rates of behavioural and emotional difficulties, particularly in
      terms of poor social relationships, over-friendliness and social disinhibition,
      preoccupations and obsessions, and high levels of anxiety and distractibility.
      CONCLUSIONS: The findings provide preliminary support for the existence of a
      specific pattern of behavioural and personality characteristics and associated
      difficulties in adults with Williams syndrome, which persist from childhood and
      often require intervention from mental health professionals. Implications for
      clinical practice are considered.

PMID- 9614480
TI  - Ethnicity in psychiatric epidemiology.

PMID- 9614481
TI  - Psychiatrists' attire revisited.

PMID- 9614482
TI  - Diagnostic criteria and functional psychosis.

PMID- 9614483
TI  - Family involvement in the care of people with psychoses.

PMID- 9614484
TI  - Calcium and heart failure.

PMID- 9614485
TI  - Alterations of calcium-regulatory proteins in heart failure.

PMID- 9614486
TI  - Alterations in calcium handling in cardiac hypertrophy and heart failure.
AB  - There is conflicting data concerning the effects of cardiac hypertrophy and
      failure on L-type Ca2+ channel density, the amplitude of the intracellular Ca2+
      transients, and the characteristics of Ca2+ sparks. These discrepancies are
      probably due to multiple factors. First, the effects of cardiac hypertrophy on
      channel expression and cell adaptation are model dependent. Even within the same
      species, the mechanisms by which cardiac hypertrophy and heart failure are
      generated (genetic alteration, pressure overload, volume overload, high rate
      pacing, etc.) influence the results obtained. Second, with many animal models and
      diseased human hearts, the disease process is not uniformly distributed
      throughout the myocardium. Third, the effects on L-type Ca2+ channel behavior and
      SR function clearly depend on the extent of disease expression. Myocardial
      contractility increases with cardiac hypertrophy whereas it decreases with heart
      failure. Thus, it is difficult to compare results from different models of
      hypertrophy and heart failure at different stages of disease. More consistent
      data is likely to be obtained from longitudinal studies using a single animal
      model of disease. The challenge before us is to develop animal models that mimic
      human disease, which can be studied longitudinally during the progression of the
      disease process. This approach coupled with continued improvement in Ca2+ imaging
      and a greater understanding of normal E-C coupling, will enable us to identify
      precisely the abnormalities in E-C coupling that occur with the development of
      cardiac hypertrophy and heart failure and define the appropriate treatment
      modalities.

PMID- 9614487
TI  - Ca2+ currents in compensated hypertrophy and heart failure.
AB  - Transmembrane voltage-gated Ca2+ channels play a central role in the development
      and control of heart contractility which is modulated by the concentration of
      free cytosolic calcium ions (Ca2+). Ca2+ channels are closed at the normal
      membrane resting potential of cardiac cells. During the fast upstroke of the
      action potential (AP), they are gated into an open state by membrane
      depolarisation and thereby transduce the electrical signal into a chemical
      signal. In addition to its contribution to the AP plateau, Ca2+ influx through L
      type Ca2+ channels induces a release of Ca2+ ions from the sarcoplasmic reticulum
      (SR) which initiates contraction. Because of their central role in excitation
      contraction (E-C) coupling, L-type Ca2+ channels are a key target to regulate
      inotropy [1]. The role of T-type Ca2+ channels is more obscure. In addition to a
      putative part in the rhythmic activity of the heart, they may be implicated at
      early stages of development and during pathology of contractile tissues [2].
      Despite therapeutic advances improving exercise tolerance and survival,
      congestive heart failure (HF) remains a major problem in cardiovascular medicine.
      It is a highly lethal disease; half of the mortality being related to ventricular
      failure whereas sudden death of the other patients is unexpected [3]. Although HF
      has diverse aetiologies, common abnormalities include hypertrophy, contractile
      dysfunction and alteration of electrophysiological properties contributing to low
      cardiac output and sudden death. A significant prolongation of the AP duration
      with delayed repolarisation has been observed both during compensated hypertrophy
      (CH) and in end-stage HF caused by dilated cardiomyopathy (Fig. 1A) [4-8]. This
      lengthening can result from either an increase in inward currents or a decrease
      in outward currents or both. A reduction of K+ currents has been demonstrated
      [6,9]. Prolonged Na+/Ca2+ exchange current may also be involved [9]. In contrast,
      there is a large variability in the results concerning Ca2+ currents (ICa). The
      purpose of this paper is to review results obtained in various animal models of
      CH and HF with special emphasis on recent studies in human cells. We focus on:
      (i) the pathophysiological role of T-type Ca2+ channels, present in some animal
      models of hypertrophy; (ii) the density and properties of L-type Ca2+ channels
      and alteration of major physiological regulations of these channels by heart rate
      and beta-adrenergic receptor stimulation; and (iii) recent advances in the
      molecular biology of the L-type Ca2+ channel and future directions.

PMID- 9614488
TI  - The role of action potential prolongation and altered intracellular calcium
      handling in the pathogenesis of heart failure.
AB  - Action potential prolongation is a common finding in human heart failure and in
      animal models of cardiac hypertrophy. The mechanism of action potential
      prolongation involves altered expression of a variety of depolarising and
      hyperpolarising currents in the myocardium. In particular, decreased density of
      the transient outward potassium current seems to play a prominent role,
      regardless of species, precipitating factors or the severity of hypertrophy. The
      decreased density of the transient outward current appears to be caused by
      reduced transcription of Kv4.2 and Kv4.3 and may be caused in part by an
      inhibitory effect of alpha-adrenoceptor stimulation. During the early stage of
      the disease process, action potential prolongation may increase the amplitude of
      the intracellular calcium transient, causing positive inotropy. We argue
      therefore, that action prolongation may be a compensatory response which may
      acutely support the compromised cardiac output. In severe hypertrophy and end
      stage heart failure however, despite continued action potential prolongation, the
      amplitude of the calcium transient becomes severely reduced. The mechanism
      underlying this event appears to involve reduced expression of calcium handling
      proteins, and these late events may herald the onset of failure. At present the
      events leading to the late changes in calcium handling are poorly understood.
      However, chronic activation of compensatory mechanisms including action potential
      prolongation may trigger these late events. In the present article we outline a
      hypothesis which describes a potential role for action potential prolongation,
      and the associated elevation in the levels of intracellular calcium, in
      maladaptive gene expression and the progression toward cardiac failure.

PMID- 9614489
TI  - Potassium channel down-regulation in heart failure.
AB  - Prolongation of action potential duration is the most consistent
      electrophysiological abnormality in myocardium and myocytes from hypertrophied
      and failing hearts. Measurements of currents in myocytes from hypertrophied and
      failing hearts indicate that, in most cases, this is due to a decrease in outward
      potassium currents. If present, a calcium-independent transient outward current
      is usually substantially reduced, but delayed rectifier and inward rectifier
      currents have also been found to be diminished. There is increasing evidence that
      potassium current down-regulation contributes significantly to the enhanced
      lability of the repolarization process in heart failure, predisposing to early
      after-depolarizations, dispersion of repolarization and ventricular arrhythmias.
      The reduction of outward potassium currents may also be involved in the enhanced
      sensitivity of failing myocardium to triggering factors like hypokalemia,
      ischemia, and antiarrhythmic agents with Class III effects. A thorough
      understanding of the mechanisms of cardiac excitability and arrhythmogenesis at
      the cellular and molecular level under normal and pathological conditions will be
      essential for the development of new pharmacological strategies to prevent sudden
      cardiac death in heart failure.

PMID- 9614490
TI  - Human myocardial Na,K-ATPase--quantification, regulation and relation to Ca.

PMID- 9614491
TI  - Sarcoplasmic reticulum in heart failure: central player or bystander?

PMID- 9614492
TI  - Calcium sequestration by the sarcoplasmic reticulum in heart failure.

PMID- 9614493
TI  - Sarcoplasmic reticulum Ca(2+)-ATPase overexpression by adenovirus mediated gene
      transfer and in transgenic mice.
AB  - The sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) is a major determinant of
      cardiac relaxation. It has been demonstrated that the steady state levels of the
      mRNA coding for this pump are reduced in human heart failure due to dilated
      cardiomyopathy. Although results regarding the protein level are controversial,
      most functional studies indicate decreased SERCA2a activity in heart failure. The
      extent to which a potential decrease in the calcium sequestering function of this
      protein could contribute to the contractile dysfunction in heart failure, and
      whether a reconstitution of SERCA2a could alleviate heart failure, are yet
      unknown. To further investigate these questions two methodological approaches
      were chosen. Adenovirus mediated gene transfer provides an approach to study
      functional consequences of SERCA2a overexpression in cardiac myocytes in vitro
      [1], and a transgenic mouse model allows the effects of cardiac overexpression of
      SERCA2a to be examined in vivo [2].

PMID- 9614494
TI  - Altered contractile function in heart failure.
AB  - The syndrome of congestive heart failure (CHF) is an entity of ever increasing
      clinical significance. CHF is characterized by a steady decrease in cardiac pump
      function which is eventually lethal. The mechanisms that underlie the decline in
      cardiac function are incompletely understood. End-stage CHF often involves the
      general loss of functional myocytes, a hyperplasia of the extracellular matrix,
      ventricular chamber remodeling, and decreased myocyte function. This review
      article focuses on the latter aspect of CHF, mechanisms of decreased myocyte
      function. Recent data from studies on human myocardial tissue obtained in the
      setting of cardiac transplantation or from studies that employed experimental
      animal models of CHF have suggested depressed myocyte function. The mechanisms
      that may be involved in the decline of myocyte contractile function include
      alterations in (i) calcium handling, (ii) myofilament function, and (iii) the
      cytoskeleton. At present, however, it is not known how or to what degree these
      alterations in cellular processes contribute to the decline of in vivo cardiac
      pump function in CHF. Accurate knowledge regarding the cellular processes that
      participate in the development of CHF is critical to the development of
      innovative strategies aimed to combat CHF.

PMID- 9614495
TI  - Modulation of contractility in human cardiac hypertrophy by myosin essential
      light chain isoforms.
AB  - Cardiac hypertrophy is an adaptive response that normalizes wall stress and
      compensates for increased workload. It is accompanied by distinct qualitative and
      quantitative changes in the expression of protein isoforms concerning
      contractility, intracellular Ca(2+)-homeostasis and metabolism. Changes in the
      myosin subunit isoform expression improves contractility by an increase in force
      generation at a given Ca(2+)-concentration (increased Ca(2+)-sensitivity) and by
      improving the economy of the chemo-mechanical transduction process per amount of
      utilised ATP (increased duty ratio). In the human atrium this is achieved by
      partial replacement of the endogenous fast myosin by the ventricular slow-type
      heavy and light chains. In the hypertrophic human ventricle the slow-type beta
      myosin heavy chains remain unchanged, but the ectopic expression of the atrial
      myosin essential light chain (ALC1) partially replaces the endogenous ventricular
      isoform (VLC1). The ventricular contractile apparatus with myosin containing ALC1
      is characterised by faster cross-bridge kinetics, a higher Ca(2+)-sensitivity of
      force generation and an increased duty ratio. The mechanism for cross-bridge
      modulation relies on the extended Ala-Pro-rich N-terminus of the essential light
      chains of which the first eleven residues interact with the C-terminus of actin.
      A change in charge in this region between ALC1 and VLC1 explains their functional
      difference. The intracellular Ca(2+)-handling may be impaired in heart failure,
      resulting in either higher or lower cytosolic Ca(2+)-levels. Thus the state of
      the cardiomyocyte determines whether this hypertrophic adaptation remains
      beneficial or becomes detrimental during failure. Also discussed are the effects
      on contractility of long-term changes in isoform expression of other sarcomeric
      proteins. Positive and negative modulation of contractility by short-term
      phosphorylation reactions at multiple sites in the myosin regulatory light chain,
      troponin-I, troponin-T, alpha-tropomyosin and myosin binding protein-C are
      considered in detail.

PMID- 9614496
TI  - Expressional analysis of the cardiac Na-Ca exchanger in rat development and
      senescence.
AB  - The cardiac Na-Ca exchanger (NCX) serves as the main calcium extrusion mechanism
      in heart muscle and is important in maintaining intracellular calcium
      homeostasis. The accumulations of NCX RNA and protein are known to be regulated
      in cardiac hypertrophy, by thyroid hormone and during postnatal development. In
      this study the temporal and spatial patterns of NCX mRNA and protein
      accumulations were examined, and nuclear run-on assays performed. NCX is highly
      expressed in late fetal and neonatal rat hearts, decreasing to adult levels by 20
      days after birth for RNA (P < 0.05, fetal and 1 neonatal day old (1 ND) versus 20
      day old (20 ND)). Maximal protein expression is seen in 19 embryonic day (ED) old
      hearts, and reaches adult levels sometime after 20 neonatal days. (P < 0.05,
      fetal versus adult). Spatially, NCX is homogenously expressed in early embryonic
      and fetal heart, followed by a decline after birth. The protein levels decline
      more slowly suggesting a long protein half-life. The lowest level of mRNA
      accumulation is seen in 6 and 18 month old animals (P < 0.05 for all time points
      before 10 neonatal days). In the 24 month old senescent rat, NCX transcripts are
      increased by almost 50% above that seen at 6 and 18 months (P < 0.05) but are not
      different from those at 15 neonatal days. Perinatal NCX expression is regulated
      transcriptionally: late fetal and neonatal hearts have high transcriptional
      activity but by 20 postnatal days, no detectable transcriptional activity can be
      demonstrated. Throughout development, at least five transcription start sites are
      used, and no significant difference in the 5' untranslated or 3' coding splice
      sites could be demonstrated, although several new cardiac splicing variants were
      identified. We also report the cloning of a 3.7 kb fragment containing the
      cardiac NCX1 promoter which is transcriptionally active in neonatal
      cardiomyocytes.

PMID- 9614497
TI  - Contribution of reverse-mode sodium-calcium exchange to contractions in failing
      human left ventricular myocytes.
AB  - OBJECTIVE: To examine the contribution of reverse mode sodium-calcium (Na-Ca)
      exchange to contractions in isolated left-ventricular myocytes from failing human
      heart. METHODS: Low resistance patch pipettes were used to dialyze cells with Na
      free or high-Na pipette solution ([Na]pipette = 0 and 20 mmol/L, respectively) to
      reduce or enhance Na-Ca exchange. Whole-cell membrane-potential, membrane-current
      and cell-shortening data were simultaneously acquired during whole-cell voltage
      clamp protocols. Thapsigargin (100 nmol/L) and nifedipine (1 mumol/L) were also
      used to inhibit sarcoplasmic reticulum (SR) Ca-ATPase and L-type Ca channels,
      respectively. RESULTS: Two types of contractions were observed. Rapid phasic
      contractions were seen in both Na-free and high-Na cells. Slow tonic contractions
      were seen only in high-Na cells. Phasic contractions demonstrated bell-shaped
      voltage dependence over the voltage range that corresponds to the activity of the
      L-type Ca channel. Although the voltage dependence of phasic contractions were
      similar Na-free and high-Na cells, phasic contractions in high-Na cells were
      larger than phasic contractions in Na-free cells. Phasic contractions were
      sensitive to inhibition of SR Ca-ATPase and L-type Ca channels. Tonic
      contractions were not inhibited by either thapsigargin or nifedipine. In
      thapsigargin-treated high-Na cells, tonic contraction magnitude increased
      exponentially with test-potential. CONCLUSIONS: The increases in phasic
      contraction magnitude observed in high-Na cells compared to Na-free cells were
      most likely due to increased SR Ca loading resulting from increased reverse-mode
      Na-Ca exchange. Our results also suggest that tonic contractions in high-Na cells
      were mediated by Ca entry via reverse-mode Na-Ca exchange and were not the result
      of either SR Ca release or L-type Ca channel activity.

PMID- 9614498
TI  - Changes in L-type calcium channel abundance and function during the transition to
      pacing-induced congestive heart failure.
AB  - OBJECTIVE: The development of congestive heart failure (CHF) is accompanied by
      left ventricular (LV) and myocyte contractile dysfunction. However, time
      dependent cellular and ionic events which contribute to the initiation and
      progression of CHF remain unclear. This study tested the central hypothesis that
      changes in L-type Ca2+ channel current (ICa) and abundance (Bmax) are early
      events in the transition to CHF. METHODS: LV fractional shortening by
      echocardiography, isolated LV myocyte shortening velocity by videomicroscopy, ICa
      by voltage-clamp, and Bmax by [3H]nitrendipine binding were determined at each
      week during the progression of pacing-induced CHF in pigs (240 bpm; n = 6/week
      for 3 weeks). Myocyte and L-type Ca2+ channel function were determined under
      basal conditions and after beta-adrenergic receptor stimulation with 25 nM
      isoproterenol. RESULTS: After 1 week of pacing, myocyte and L-type Ca2+ current
      responses to beta-adrenergic receptor stimulation were reduced by 20% from
      control values and was accompanied by over a 210% increase in plasma
      catecholamine levels. After 2 weeks of pacing, reductions in LV fractional
      shortening and myocyte shortening velocity from control values (20 +/- 1 vs. 34
      +/- 2% and 36.7 +/- 2.9 vs. 50.6 +/- 2.4 microns/s, respectively, P < 0.05) were
      paralleled by decreased ICa (2.47 +/- 0.10 vs. 3.63 +/- 0.25 pA/pF, P < 0.02) and
      Bmax (149 +/- 16 vs. 180 +/- 12 fmol/mg, P < 0.03). After 3 weeks of pacing, LV
      fractional shortening was reduced by over 50%, myocyte shortening velocity by
      37%, and ICa and Bmax were reduced by over 25% from control values. Furthermore,
      after 3 weeks of pacing, the ICa/Bmax ratio was reduced from control values (16.2
      +/- 0.9 vs. 20.6 +/- 1.2 [fA/pF]/[fmol/mg], P < 0.03), which suggests functional
      defects in the remaining L-type Ca2+ channels. CONCLUSIONS: An early event during
      the transition to pacing-induced CHF was diminished beta-adrenergic receptor
      augmented L-type Ca2+ current, which was followed by an absolute loss of steady
      state L-type Ca2+ current and channel abundance. The development of severe CHF
      was accompanied by a loss of Ca2+ carrying capacity through residual channels.
      These unique findings suggest that a contributory molecular mechanism for the
      initiation and progression of CHF is changes in the structure and function of the
      L-type Ca2+ channels.

PMID- 9614499
TI  - Single-channel properties of L-type calcium channels from failing human
      ventricle.
AB  - OBJECTIVE: The aim of our study was to analyse the single-channel properties of L
      type calcium channels from failing human heart and to compare them to the
      respective animal data. Furthermore, we intended to evaluate the feasibility of
      future single-channel studies on the role of calcium channels in the
      pathophysiology of heart failure. METHODS: Single L-type calcium channels were
      recorded in ventricular myocytes from explanted failing human heart, using the
      cell-attached configuration of the patch-clamp technique. RESULTS: One or more
      successful registrations of calcium channels could be obtained in 11 of 19 cell
      isolations. Determination of single-channel conductance yielded a mean value of
      16.6 +/- 1.2 pS (70 mM Ba2+ as the charge carrier) under control conditions and
      23.7 +/- 2.8 pS in presence of the calcium-channel agonist FPL 64176. The rapid
      gating process could be described by a C<-->C<-->O gating scheme. Slow gating
      analysis revealed a highly significant clustering of active and non-active
      sweeps. CONCLUSION: Single-channel measurements of L-type calcium channels in
      human failing ventricle are feasible and reproducible despite the varying patient
      characteristics. Their channel properties are qualitatively comparable to those
      found in other mammals. Whether there are quantitative differences due to the
      underlying heart failure can be elucidated in further studies.

PMID- 9614500
TI  - Characterization of excitation-contraction coupling in conscious dogs with pacing
      induced heart failure.
AB  - OBJECTIVE: In isolated cardiac preparations of non-failing hearts from different
      species, including man, there is a positive force-frequency relation which is
      reversed into a negative relation in preparation from failing hearts. Whether or
      not such relations between ventricular function and heart rate hold true in the
      in situ heart is not clear at present. Mechanical restitution and
      postextrasystolic potentiation might serve as alternative measures of excitation
      contraction coupling. METHODS: Eleven dogs were instrumented with a left
      ventricular micromanometer, ultrasonic crystals for the measurement of regional
      wall thickness, two hydraulic occluders around the descending aorta and the
      inferior caval vein, and left atrial and ventricular pacing leads with a
      subcutaneous pacemaker. Left ventricular dP/dtmax, as an isovolumic phase index,
      and systolic wall thickening, as an ejection phase index, were plotted versus
      heart rate, and heart rate was increased by left atrial pacing from rest to 200
      min-1 in increments of 25 min-1. In a subset of dogs, left ventricular filling
      was controlled and the frequency range expanded by the bradycardic agent UL-FS
      49. Measurements were performed in the presence and absence of autonomic blockade
      (hexamethonium, atropine). Mechanical restitution and postextrasystolic
      potentiation were determined as normalized dP/dtmax and systolic wall thickening,
      respectively, of the extra- and postextrasystolic beat versus defined variations
      of the extrasystolic time interval (250-550 ms). Following control studies, heart
      failure was induced by rapid left ventricular pacing at 250 min-1 for 20 days +/-
      6 (SD) and measurements repeated. Isolated left ventricular trabeculae from non
      failing and failing hearts were studied during stimulation at 0.2-4 Hz. RESULTS:
      Only with filling control and in the absence of autonomic blockade, was there a
      slightly positive relation between dP/dtmax and heart rate in the control state.
      Otherwise, the relation of dP/dtmax to heart rate was flat both in the control
      state and in heart failure. The relation between systolic wall thickening and
      heart rate in the control state was negative, unless filling was controlled, and
      it was flat in heart failure. In contrast, the time constants of mechanical
      restitution and postextrasystolic potentiation were increased significantly with
      heart failure from 91 +/- 25 (SD) to 164 +/- 13 ms and from 107 +/- 18 to 156 +/-
      4 ms, respectively, for dP/dtmax and from 76 +/- 22 to 162 +/- 10 ms and from 101
      +/- 17 to 160 +/- 17 ms, respectively, for systolic wall thickening. These time
      constants were, however, insensitive to UL-FS 49 and autonomic blockade. There
      was a negative force-frequency relation in left ventricular trabeculae from non
      failing hearts at higher calcium concentrations, where it was flat in trabeculae
      from failing hearts. CONCLUSION: Time constants of mechanical restitution and
      postextrasystolic potentiation are more sensitive than the steady state relation
      of ventricular function and heart rate to characterize the impairment of
      excitation-contraction coupling in heart failure.

PMID- 9614501
TI  - Early changes in excitation-contraction coupling: transition from compensated
      hypertrophy to failure in Dahl salt-sensitive rat myocytes.
AB  - OBJECTIVE: The aims were to (1) define the early changes in excitation
      contraction coupling during the transition from cardiac hypertrophy to heart
      failure, and (2) to clarify the causal relationship between mechanical
      dysfunction and abnormal Ca2+ handling in the Dahl salt-sensitive rat model.
      METHODS: Myocardial contractile function was assessed in whole heart perfusion
      studies. In separate experiments, isolated left ventricular myocytes from Dahl
      salt-sensitive (DS) and Dahl salt-resistant (DR) rats were paced at a
      physiological rate of 5Hz and cell shortening (CS) and [Ca2+]i measured
      simulataneously by video-edge detection and fura-2 fluorescence. RESULTS: DS
      hearts developed hypertrophy after 4 weeks of a high-salt diet (4WHSD), as
      indicated by a 26% increase (p < 0.01) in the heart to body weight ratio and a
      21% increase (p < 0.01) in cell width. Heart failure developed after 12 weeks of
      a high-salt diet (12WHSD), as indicated by an 11% increase (p < 0.01) in the lung
      wet to dry weight ratio. Furthermore, in DS-12WHSD hearts, the diastolic pressure
      volume relationship had shifted rightward. DR rats did not develop hypertension
      and seved as age-matched controls. A 31% (p < 0.05) increase in the %CS in DS
      4WHSD myocytes compared to DR-4WHSD myocytes with a trend of a parallel increase
      in Ca2+ transient amplitude was found. There was no difference in the Ca2+
      transient parameters between DR and DS at 12WHSD, but an 18% (p < 0.01) decrease
      occurred in peak [Ca2+]i in DS myocytes between 4WHSD and 12WHSD. In DS-12WHSD,
      the time to peak shortening and the time from peak shortening to 50% and 90%
      relaxation was significantly prolonged by 27%, 44%, and 38%, respectively, as
      compared to the age-matched DR myocytes. CONCLUSION: Our results indicated that:
      (I) normal Ca2+ homeostasis is preserved at the stage of compensated hypertrophy;
      (2) the early signs of isolated myocyte dysfunction were a prolongation of the
      shortening and relaxation time course without an abnormal time course of the Ca2+
      transient. Thus, in the hypertensive Dahl salt rat model, abnormal Ca2+ handling
      appears neither to precede nor initiate the transition to failure.

PMID- 9614502
TI  - Frequency dependence of Ca2+ release from the sarcoplasmic reticulum in human
      ventricular myocytes from end-stage heart failure.
AB  - OBJECTIVES: Human cardiac muscle from failing heart shows a decrease in active
      tension development and a rise in diastolic tension at stimulation frequencies
      above 50-60 beats/min due to both systolic and diastolic dysfunction. We have
      investigated underlying changes in cellular [Ca2+]i regulation. METHODS: Single
      ventricular myocytes were isolated enzymatically from the explanted hearts of
      transplant recipients with ischemic cardiomyopathy (nhearts = 5 ncells = 15) or
      dilated cardiomyopathy (nhearts = 6, ncells = 19). Cells were studied during
      whole-cell patch clamp with fluo-3 and fura-red as [Ca2+]i indicators (36 +/- 1
      degrees C). RESULTS: In current clamp mode (action potential recording), the
      amplitude of Ca2+ release from the sarcoplasmic reticulum (SR) decreased at
      stimulation frequencies above 0.5 Hz; this decrease was more pronounced for cells
      from dilated cardiomyopathy. Diastolic [Ca2+]i increased at 1 and 2 Hz for both
      groups. Action potential duration (APD90) decreased with frequency in all cells;
      in addition there was a drop in plateau potential of 10 +/- 1 mV for cells from
      ischemic cardiomyopathy and of 13 +/- 2 mV for cells from dilated cardiomyopathy.
      In voltage clamp mode the L-type Ca2+ current showed reversible decrease during
      stimulation at 1 and 2 Hz. Recovery from inactivation during a double pulse
      protocol was slow (75 +/- 3% at 500 ms, 89 +/- 3% at 1000 ms) and followed the
      decay of the [Ca2+]i transient. CONCLUSIONS: The negative force-frequency
      relation of the failing human heart is due to a decrease in Ca2+ release of the
      cardiac myocytes at frequencies > or = 0.5 Hz, more pronounced in dilated than in
      ischemic cardiomyopathy. Inhibition of ICaL at higher frequencies, at least
      partially related to an increase in diastolic [Ca2+]i, will contribute to this
      negative staircase because of a decrease in the trigger for Ca2+ release, and of
      decreased loading of the SR.

PMID- 9614503
TI  - Non-uniform prolongation of intracellular Ca2+ transients recorded from the
      epicardial surface of isolated hearts from rabbits with heart failure.
AB  - OBJECTIVES: To study the time course of Ca2+ transients recorded from the left
      ventricular epicardial surface of isolated hearts from rabbits with heart failure
      and to correlate the results with mechanical function. METHODS: Heart failure was
      induced in the rabbit 8 weeks after coronary ligation (n = 17) with 13 controls.
      Echocardiography was used to assess in vivo left ventricular dysfunction. The
      fluorescent indicator Indo-1 was loaded into isolated Langendorff-perfused hearts
      and Ca2+ transients were recorded from 15 sites over the left ventricular
      epicardial surface using a single core light guide. The time course of the Ca2+
      transients was analysed and the duration measured and correlated with in vitro
      mechanical function. RESULTS: Significant mechanical dysfunction was produced in
      this model of heart failure. The mean duration of the Ca2+ transients obtained
      from failing hearts was prolonged (156.2 +/- 3.2 ms) when compared to controls
      (124.9 +/- 2.6 ms, P < 0.001). Delayed relaxation as measured by the maximum rate
      of intraventricular pressure decay was significantly correlated with the
      prolonged Ca2+ transients (r = -0.63, P < 0.001). In addition, there was
      increased variation of the Ca2+ transient duration in the failing hearts.
      CONCLUSIONS: Coronary artery ligation-induced heart failure is associated with
      changes in the surviving myocardium which result in a non-uniform prolongation of
      Ca2+ transient duration. This suggests that there is a regional heterogeneity to
      the abnormal intracellular Ca2+ handling in heart failure.

PMID- 9614504
TI  - Sarcoplasmic reticulum Ca2+ ATPase promoter activity during endothelin-1 induced
      hypertrophy of cultured rat cardiomyocytes.
AB  - OBJECTIVES: Characterization of an in vitro model of endothelin-1 induced
      hypertrophy of cultured neonatal rat ventricular myocytes and subsequent analysis
      of transcription regulation of the rat promoter of the sarcoplasmic reticulum
      Ca2+ ATPase gene. METHODS: Neonatal rat ventricular myocytes were cultured in
      serum free medium and hypertrophy was induced by addition of endothelin-1 to 10(
      8) M up to 48 h. Hypertrophy was characterized biochemically, and gene expression
      regulation was evaluated by Northern blotting. A sarcoplasmic reticulum Ca2+
      ATPase promoter fragment, isolated from a rat library was cloned in a reporter
      vector. Promoter activity during hypertrophy was assessed after transfection of
      the reporter plasmid to cultured cardiomyocytes. RESULTS: Stimulation with
      endothelin-1 resulted in increased cell size, as indicated by protein/DNA ratio
      as well as by augmented protein synthesis. When compared to angiotensin II or
      alpha 1-adrenergic agonist, endothelin-1 was the strongest inducer of hypertrophy
      (protein/DNA ratio) after 48 h of stimulation. Endothelin-1 induced hypertrophy
      was accompanied by a twofold increase in total RNA content per cell as well as to
      increased glyceraldehydephosphate dehydrogenase mRNA levels. The level of atrial
      natriuretic factor mRNA was increased more than twofold, relative to
      glyceraldehydephosphate dehydrogenase, while the expression of the sarcoplasmic
      reticulum Ca2+ pump and phospholamban genes was decreased (by 26 and 49%,
      respectively) after induction of hypertrophy by stimulation with endothelin-1. In
      the same model, a 1.9 kb sarcoplasmic reticulum Ca2+ pump gene promoter fragment
      (including 0.4 kb of the 5' UTR of the mRNA) directed down-regulation of the
      expression of the reporter gene to the same magnitude as endogenous Ca2+ pump
      mRNA relative to glyceraldehydephosphate dehydrogenase mRNA. However, absolute
      mRNA level per cell did not change for either the reporter gene or the endogenous
      Ca2+ pump. CONCLUSIONS: Endothelin-1 can induce phenotypic changes in cultured
      rat ventricular myocytes that are reminiscent of hypertrophy in vivo. In this
      model, a 1.9 kb sarcoplasmic reticulum Ca2+ pump promoter fragment directed gene
      expression of a reporter gene identical to the endogenous regulation of the Ca2+
      pump. Furthermore, expression of the Ca2+ pump during hypertrophy was only
      downregulated when compared to (increased levels of) glyceraldehydephosphate
      dehydrogenase mRNA, but absolute Ca2+ ATPase mRNA amounts remained unchanged.
      This suggests that the Ca2+ pump promoter is not responding to the increase in
      transcriptional activity that accompanies hypertrophy.

PMID- 9614505
TI  - Calcium uptake by the sarcoplasmic reticulum, high energy content and
      histological changes in ischemic cardiomyopathy.
AB  - OBJECTIVES: Sarcoplasmic reticulum (SR) Ca2+ uptake, myocardial high energy
      content and histology were examined in different zones of hearts from patients
      with ischemic cardiomyopathy. METHODS AND RESULTS: Unfractionated homogenates
      were prepared from left ventricular samples obtained in three zones of each
      heart: an infarct-remote zone, an outer peri-infarct zone, and an inner peri
      infarct zone. Oxalate-supported 45Ca2+ uptake was measured at 37 degrees C using
      a filtration method. Maximum rate (Vmax) of uptake in absence or in presence of
      ryanodine was lower in inner peri-infarct (7.4 +/- 0.7 and 9.5 +/- 0.8 nmol min-1
      mg-1 of protein, respectively; mean +/- SEM) and outer peri-infarct tissues (8.8
      +/- 0.8 and 12.0 +/- 0.8 nmol min-1 mg-1) than in infarct-remote myocardium (12.7
      +/- 2.1 and 15.8 +/- 2.2 nmol min-1 mg-1). The apparent affinity constants for
      Ca2+ (KCa) as well as the Hill coefficients were not different. Homogenate DNA
      (1.6 +/- 0.1, 1.6 +/- 0.1 and 1.7 +/- 0.1 mg/g of remote, inner peri-infarct and
      outer peri-infarct myocardium, respectively) and adenine nucleotides contents
      (ATP: 15 +/- 1.3, 14 +/- 0.8 and 15 +/- 1.0 mumol/g dry weight, respectively)
      were similar in all tissues. Fibrosis was increased in inner peri-infarct tissue
      (37 +/- 6%; vs. 13 +/- 2% and 12 +/- 2% in both remote and outer peri-infarct
      tissues, respectively), but the number of abnormal cells was not significantly
      different. CONCLUSION: The decrease of Ca2+ uptake in ischemic cardiomyopathy is
      not homogeneous in the ventricular wall, and reflects a decreased number/activity
      of SR Ca(2+)-ATPase, without altered Ca(2+)-affinity or increased Ca2+ leakage
      through ryanodine receptors.

PMID- 9614506
TI  - Relationship between the increase in Ca2+ transient and contractile force induced
      by angiotensin II in aequorin-loaded rabbit ventricular myocardium.
AB  - OBJECTIVES: Pieces of evidence have been accumulating that imply a crucial role
      of angiotensin II (Ang II) in initiation and progress of heart failure, but the
      signalling processes subsequent to Ang II receptor activation in cardiac myocytes
      are complex and still controversial. We examined the effects of Ang II on the
      relationship between the intracellular Ca2+ transient and isometric contraction
      in mammalian ventricular myocardium. METHODS: Isolated rabbit ventricular
      papillary muscle was loaded with the Ca2+ sensitive bioluminescent protein
      aequorin and electrically stimulated at a rate of 0.5 Hz at 37 degrees C.
      RESULTS: Ang II (10(-8)-10(-6) M), in the presence of bupranolol (3 x 10(-7) M)
      and prazosin (10(-7) M), elicited a positive inotropic effect (PIE) in
      association with an increase in the peak Ca2+ transient. The maximal PIE of Ang
      II was about 30% of the isoproterenol-induced maximum (ISOmax), while the maximal
      increase in the peak Ca2+ transient induced by Ang II was only 7% of ISOmax. Ang
      II tended to prolong the duration of contraction (both time to peak force and
      relaxation time) but did not produce a discernible change in the duration of Ca2+
      transient. The relationship between the amplitude of Ca2+ transient and peak
      force was shifted to the left by Ang II, as compared with the relationship for
      elevation of [Ca2+]o (2.5-15.0 mM). The PIE and the increase in the amplitude of
      Ca2+ transient induced by Ang II were abolished by a selective angiotensin type 1
      (AT1) receptor antagonist losartan (10(-5) M) but were not affected by a
      selective AT2 receptor antagonist PD123319 (10(-6) M). CONCLUSIONS: These results
      indicate that Ang II elicits a PIE through a dual mechanism via activation of AT1
      receptors in rabbit ventricular myocardium: by an increase in the amplitude of
      Ca2+ transient; and in addition by an increase in the myofilament Ca2+
      sensitivity.

PMID- 9614507
TI  - The role of cAMP in the frequency-dependent changes in contraction of guinea-pig
      cardiomyocytes.
AB  - OBJECTIVES: beta-Receptor desensitisation, low basal cAMP, and a negative force
      frequency relationship are characteristic changes in human heart failure.
      Isolated cardiomyocytes from noradrenaline-treated guinea pigs also show these
      features. We tested the hypothesis that low basal cAMP underlies the loss of
      contractile response to increasing stimulation frequency in this model. METHODS:
      Isolated cardiomyocytes were obtained from noradrenaline-treated (NA) and sham
      operated (SHAM) guinea pigs. They were stimulated from 0.1-2 Hz and contraction
      amplitude was monitored with a video edge-detection system. RESULTS: NA cells had
      less positive amplitude-frequency responses (AFR) compared to SHAMs at 2 mM (P =
      0.002, n = 17), or midrange Ca2+ concentrations (EC40-EC60) (P < 0.001, n = 13).
      When the cAMP agonist, 8-CPT-cAMP (CPT, 10 microM) or high Ca2+ (above EC75) was
      added to NA cells the AFR was normalised to that of SHAM myocytes (NA vs. SHAM P
      = ns). In control experiments the cAMP antagonists, Rp-cAMPS (Rpc) and Rp-8-CPT
      cAMPS (Rp8, 100 microM), blocked the positive inotropic effects of CPT at 0.5 Hz
      (control pD2 = 4.36 +/- 0.06, Rp8 pD2 = 3.68 +/- 0.08, P < 0.0001), n = 6
      paired). Rpc (100 microM) completely but reversibly blocked the effect of maximal
      isoprenaline in control experiments (P < 0.0001). Neither antagonist reduced the
      AFR compared to time-matched controls (P = ns, n = 6). Blockade of SERCA2a with
      thapsigargin resulted in a significant reduction in the AFR (ANOVA P < 0.0001).
      CONCLUSIONS: The results are consistent with sarcoplasmic reticulum (SR) function
      being a more important determinant of the amplitude-frequency relationship than
      tonic levels of cAMP under basal conditions. Reversal of AFR depression by CPT
      may result from stimulation of SR Ca2+ uptake.

PMID- 9614509
TI  - The National Diabetic Retinopathy Laser Treatment Audit: implications for
      clinical practice in 1998.

PMID- 9614508
TI  - Preserved Frank-Starling mechanism in human end stage heart failure.
AB  - OBJECTIVE: The goal of the present study was to examine the ability of failing
      myocardium to respond to enhanced preload with an increase in force development.
      METHODS: The effect of various preload conditions (2.5-15 mN) on force
      development was studied in right ventricular trabeculae carneae from explanted
      human failing hearts with ischemic cardiomyopathy (ICM, n = 5, 42 preparations)
      or idiopathic dilated cardiomyopathy (DCM, n = 9, 77 preparations). To determine
      the severity of cardiac impairment we measured the positive inotropic effect of
      beta-adrenoceptor stimulation and calcium (ISO/Ca2+ ratio) and the expression of
      atrial natriuretic peptide (ANP) mRNA in all hearts. RESULTS: (1) Force of
      contraction increased with stepwise augmentation of preload (length at 2.5 mN
      preload to length of maximal force development) from 3.7 +/- 0.5 (ICM) and 2.7 +/
      0.4 (DCM) to 8.3 +/- 0.9 and 6.5 +/- 0.8 mN/mm2, respectively (p < 0.05). (2)
      The ISO/Ca2+ ratio was 0.40 +/- 0.04 (ICM) and 0.35 +/- 0.03 (DCM), respectively.
      (3) ANP mRNA was expressed in all preparations, albeit at greatly varying levels
      (ICM 22.5 +/- 6.1 and DCM 18.7 +/- 4.7 normalized arbitrary units). (4)
      Contraction experiments performed in left ventricular tissue (n = 3, 32
      preparations) essentially confirmed the results. CONCLUSION: The Frank-Starling
      mechanism is preserved in terminally failing human hearts irrespective of the
      underlying etiology. We found no relation between the severity of cardiac
      impairment as assessed by either ANP expression or the ISO/Ca2+ ratio and the
      ability of failing human myocardium to respond to enhanced preload with an
      increase in force development.

PMID- 9614510
TI  - Reliable and accessible reviews of the evidence for the effect of health care:
      the role of the Cochrane Collaboration and the CONSORT statement.

PMID- 9614511
TI  - Glaucoma: fielding progressive disease.

PMID- 9614512
TI  - Pituitary tumours: recommendations for service provision and guidelines for
      management of patients. Committee on Endocrinology of the Royal College of
      Physicians and the Society for Endocrinology, and the Research Unit of the Royal
      College of Physicians.

PMID- 9614513
TI  - The Doyne Lecture. Congenital cataract: the history, the nature and the practice.

PMID- 9614514
TI  - A study of the hydroxyapatite orbital implant drilling procedure.
AB  - PURPOSE: The hydroxyapatite orbital implant has been introduced as a buried,
      integrated implant for use in the anophthalmic patient. The second stage of the
      procedure involves drilling the implant and inserting a motility peg that allows
      direct coupling of the artificial eye to the implant. Other authors have
      advocated an assessment of implant vascularity by imaging prior to drilling. We
      aimed to see whether our practice of drilling after a predetermined time interval
      without assessment of implant vascularity would result in a higher complication
      rate. We also aimed to determine how successful the drilling procedure was in
      improving both the motility and the stability of the artificial eye. METHODS: The
      notes of 41 consecutive patients who underwent drilling were studied to determine
      the time interval between implantation with a hydroxyapatite sphere and drilling,
      the nature of any complications and any further surgical procedures undertaken. A
      postal questionnaire was sent to all patients asking them to grade the motility
      of their implant before and after drilling, and to state whether or not there had
      been any improvement in the stability of their artificial eye. RESULTS: The most
      frequent complication encountered was extrusion of the motility peg, which
      occurred in 3 patients. A total of 5 patients required redrilling. There was an
      80% response rate to the questionnaire. Ninety-one per cent of patients felt that
      there had been an improvement in the motility of their artificial eye and 76%
      felt that the stability of their artificial eye had been improved. CONCLUSION:
      Pegging of the hydroxyapatite implant improves both the motility and the
      stability of the artificial eye in the majority of cases. Complications are
      infrequent and minor. If sufficient time is allowed after implantation for full
      implant vascularity to occur, it is not necessary to perform imaging studies.
      This practice does not result in an increase in complications, and significantly
      reduces the expense of the procedure.

PMID- 9614515
TI  - The management of solitary trichoepithelioma versus basal cell carcinoma.
AB  - Currently, all lesions diagnosed clinically as basal cell carcinoma (BCC) are
      treated by the excision of the lesion with 3-4 mm margins followed by
      histopathological examination to assess clearance and confirm the diagnosis. We
      present the findings of surgical incisional and excisional biopsy of three young
      patients diagnosed on clinical examination as having BCC, who were found on
      histological examination to have trichoepithelioma. Whilst it may be possible to
      distinguish the features of trichoepithelioma in incisional biopsy specimens on
      morphological grounds alone it is often difficult, and immunohistochemical
      staining, to delineate the features of the basement membrane, provides useful
      additional information in the histological diagnosis. As trichoepithelioma is
      more common in the young it should be considered in the differential diagnosis in
      young patients presenting with BCC-like lesions of the periocular tissues. This
      subgroup of patients should have incisional biopsy carried out, and if the
      diagnosis of trichoepithelioma is confirmed the lesion may be excised with a
      small margin of healthy tissue, thereby facilitating surgical repair.

PMID- 9614516
TI  - Levator palpebrae superioris fibre size in normals and patients with congenital
      ptosis.
AB  - A study of the histochemical staining of levator palpebrae superioris (LPS) was
      undertaken to measure the muscle fibre size in normal individuals and in patients
      with congenital dystrophic ptosis in order to see whether there is an alteration
      in muscle fibre size in congenital ptosis. Eight LPS specimens were obtained: 4
      from normal patients (3 from normal levator divided in a bilateral brow
      suspension procedure and 1 from an exenteration specimen) and 4 from levator
      resection procedures for treatment of unilateral congenital ptosis. Cryostat
      sections from these specimens were stained histochemically to reveal muscle fibre
      types. The orthogonal diameters were measuring using a computer-generated program
      and the two groups compared using the Mann-Whitney mu-test. No statistically
      significant difference in muscle fibre diameter was found between normals and
      patients with congenital ptosis. There was also no change in the distribution or
      range of muscle fibre diameter in patients with congenital ptosis. Our findings
      do not support the classification of congenital ptosis as a dystrophy.

PMID- 9614517
TI  - Necrotising fasciitis as a complication of botulinum toxin injection.
AB  - PURPOSE: To highlight the need for early diagnosis and treatment of the rare
      condition of necrotising fasciitis as a complication of botulinum toxin
      injection, and to illustrate that injections in immunocompromised patients carry
      a rare but serious risk. RESULTS AND METHODS: A case report is presented of an 80
      year-old woman suffering from blepharospasm and chronic myeloid leukaemia, who
      developed necrotising fasciitis 3 days after a botulinum toxin injection.
      CONCLUSIONS: Chronic debilitating processes such as diabetes, alcoholism and
      polymyositis have been suggested as predisposing factors in the development of
      necrotising fasciitis. We believe this is the first reported case of necrotising
      fasciitis occurring secondary to a botulinum toxin injection. The fact that this
      infection extended through the fascial planes and led to the death of muscle was,
      probably, because an inoculum was introduced directly into the muscle at the time
      of botulinum toxin treatment. This may have led to its deep spread and difficulty
      in debriding the area. Chronic myeloid leukaemia does not in itself cause
      significant immunosuppression, but our patient was on anti-proliferative
      treatment and had a low leucocyte count, which may have been a predisposing
      factor in this case.

PMID- 9614518
TI  - Evaluation of optic disc cupping using high-resolution ocular ultrasound.
AB  - BACKGROUND/PURPOSE: The new Biovision B-Scan Probe has greater resolution than
      its predecessors because of its posteriorly placed focus (25 mm inside the eye)
      and the consequent reduction in size of the sound field. We investigated the
      accuracy, reproducibility and test-retest variability of two-dimensional optic
      cup measurements using this new-generation B-scanner. METHODS: One randomly
      selected eye of 20 patients underwent five repeated measurements of vertical
      (VOCD) and horizontal optic cup diameters (HOCD), and optic cup depth, using
      confocal scanning laser tomography (Heidelberg Retinal Tomograph) and high
      resolution ultrasound (Biovision, Chiron Vision, UK) on two separate occasions.
      There was one operator per instrument who was masked to all clinical data and
      previous measurements. Accuracy of ultrasound readings was quantified by
      comparing the results with those of Heidelberg Retinal Tomography (HRT). RESULTS:
      The 95% confidence interval for the bias of echographic vertical and horizontal
      cup diameter measurements was -95 +/- 48 microns and -19 +/- 72 microns
      respectively, and -87 +/- 328 microns for cup depth readings. The indices of
      reproducibility (mean coefficient of repeatability +/- SD) were: VOCD: 177 +/-
      105 microns [B-scan] 209 +/- 100 microns [HRT]; HOCD: 179 +/- 61 microns [B
      scan], 205 +/- 101 microns [HRT]; cup depth: 206 +/- 63 microns [B-scan], 204 +/-
      124 microns [HRT]. Ninety-five per cent limits of agreements between initial and
      retest values for ultrasound were 18 +/- 136 microns [VOCD], 2 +/- 144 microns
      [HOCD] and 4 +/- 156 microns [cup depth], compared with 1 +/- 104 microns [VOCD],
      20 +/- 102 microns [HOCD] and 3 +/- 168 microns [cup depth] for scanning laser
      tomography. CONCLUSION: The results demonstrate that measurements of optic cup
      diameter and depth using ultrasound correlate strongly with corresponding HRT
      readings. These echographic measurements are reproducible, and not subject to
      clinically meaningful test-retest variability. This technique of measuring two
      dimensional cup parameters does not require expensive specialist equipment and
      has many potential clinical applications which are discussed.

PMID- 9614519
TI  - Carotid artery Doppler ultrasonography in retinal macroaneurysms.
AB  - It is postulated that retinal arterial macroaneurysms (RAMs) occur at the site of
      incomplete embolic occlusion of a branch retinal artery. Embolic events of the
      retinal vessels are related to the state of the carotid artery tree and therefore
      Doppler ultrasonography of the carotid arteries in these patients is of
      particular interest. We have examined 13 patients with retinal artery
      macroaneurysms with carotid artery Doppler ultrasonography (CADU). Eight of these
      patients (61.5%) exhibited atheromatous plaques on the same side as the RAM with
      a moderate degree of arterial narrowing. Although our group of patients did not
      show advanced carotid artery disease, alterations of the arterial wall found at
      the level of the carotid artery were higher than expected in a similar
      hypertensive population. To our knowledge this is the first study of the carotid
      arterial tree in these patients. Our results support the theory that RAMs may be
      of embolic origin. Furthermore they demonstrate that CADU is a useful
      investigation in patients with RAMs.

PMID- 9614520
TI  - What effect does laser photocoagulation have on driving visual fields in
      diabetics?
AB  - Although laser panretinal photocoagulation (PRP) for proliferative diabetic
      retinopathy is known to cause peripheral field constriction, the risks of failing
      the UK driving field test following treatment are currently unclear as the small
      number of previous studies have conflicting results. Following PRP using only
      argon laser with a 500 microns spot size, both uniocular and binocular Esterman
      visual fields from 60 diabetic patients were assessed by the Chairman of the
      Visual Standards Sub-Committee of the Royal College of Ophthalmologists. Forty
      two per cent of uniocular fields from treated eyes failed. Twelve per cent of
      binocular fields from those having bilateral PRP failed. Type II diabetes was
      associated with a significant increase in the risk of failure. Although there is
      a high risk of failure in any given treated eye, 88% of diabetics will pass a
      binocular field test, even if both eyes are treated.

PMID- 9614521
TI  - The National Diabetic Retinopathy Laser Treatment Audit. I. Maculopathy.
AB  - The National Diabetic Retinopathy Laser Treatment Audit is a prospective survey
      of laser treatment for diabetic retinopathy throughout the United Kingdom. This
      paper describes the methodology of the study and presents data on 546 patients
      who were undergoing their first photocoagulation treatment for diabetic
      maculopathy (without proliferative retinopathy) during a 2 month period in 1995.
      Validation of the level of participation, patient demographic features, sources
      of referral, the level of systematic screening and waiting times are described.
      Maculopathy was detected as a result of systematic screening in 65.2%, whilst
      12.3% of cases presented symptomatically. The percentage of cases treated within
      8 weeks of listing was 83.1%, whilst 7% waited for more than 12 weeks for their
      laser treatment. The retinopathy features and the type of treatment given are
      also described. The maculopathy was said to be predominantly exudative in nature
      in 69.8% of cases, and 96.2% of these eyes were treated with focal macular laser.
      The maculopathy was said to be diffusely oedematous in nature in 8.6% of cases,
      and 78.7% of these eyes were treated with grid macular laser.

PMID- 9614522
TI  - The National Diabetic Retinopathy Laser Treatment Audit. II. Proliferative
      retinopathy.
AB  - The National Diabetic Retinopathy Laser Treatment Audit is a prospective survey
      of laser treatment for diabetic retinopathy throughout the United Kingdom. This
      paper presents data on 284 patients who were undergoing their first panretinal
      photocoagulation for proliferative retinopathy during a 2 month period in 1995,
      describing the demographic features, the level of systematic screening, the
      sources of referral, and the waiting times. For those cases where proliferative
      retinopathy was present at the first ophthalmology outpatient visit, the
      retinopathy was detected as a result of systematic screening in 46.8%, whilst
      28.7% presented symptomatically. Of these patients 28.4% waited for more than 12
      weeks from referral to the time of laser treatment, but once the patient had been
      listed for laser treatment this was performed within 8 weeks in 95.3%. The
      retinopathy features and the type of treatment given are also described. Compared
      with the DRS and ETDRS recommendations, at least 32.5-40.2% of eyes may be
      undertreated initially, and for those with high-risk characteristics these
      figures were at least 30.8-38.5%.

PMID- 9614523
TI  - System analysis in vision.

PMID- 9614524
TI  - Bilateral Kimura's disease with devastating visual outcome.
AB  - Kimura's disease is a chronic inflammatory disease involving connective tissues.
      We treated a patient with bilateral periocular Kimura's disease causing eyelid
      deformity and exophthalmos for over 20 years. She has been operated on 23 times
      and biopsies were taken and studied histologically. The disease continued despite
      the multiple surgical excisions. The consequent exophthalmos and lid changes
      caused lagophthalmos that resulted in severe visual impairment due to chronic
      bilateral corneal exposure. Kimura's disease may have a devastating effect on
      visual function.

PMID- 9614525
TI  - Immediate response of retinal vessels to isometric muscle contraction.
AB  - Isometric muscle contraction results in a rise in systemic blood pressure (BP)
      and constriction of retinal arterioles. The responses in the anaesthetised cat
      have been studied to provide further insight into the results of human studies.
      Constriction (median 3.43% of control values) and dilatation (median 4.17% of
      control values) were observed; the onset of constriction was delayed by 4 s
      compared with dilatation. There was spatial and temporal variation in the
      observed calibre changes, and inter-experimental variation in the calibre
      change/BP ratio. It is concluded that the response of retinal arterioles of
      measurable size is not unified, and that the two modes of response differ in
      mechanism.

PMID- 9614526
TI  - Assessment of visual function in idiopathic intracranial hypertension: a
      prospective study.
AB  - The visual function of 35 patients with a diagnosis of idiopathic intracranial
      hypertension was assessed prospectively over a 3 year period. In assessing the
      visual function of cases of idiopathic intracranial hypertension a number of
      tests were employed including visual field assessment with Humphrey and Goldmann
      perimeters and documentation of visual acuity and contrast sensitivity. Loss of
      visual function is the only serious complication and may occur early or late in
      the course of the condition. An appropriate and sensitive clinical assessment
      regime is therefore of importance in the outpatient situation. Visual field
      assessment was documented as the most sensitive to detection of visual loss, with
      statistically greater sensitivity in comparison with visual acuity and contrast
      sensitivity testing. Detection of asymptomatic visual loss indicates the
      necessity for visual monitoring to ensure detection of insidious visual loss. The
      types of visual field defects noted in this study were typical of anterior optic
      nerve pathology of raised intracranial pressure and commonly included arcuate
      defects, nasal steps and global constriction. Visual loss was noted at
      presentation and during follow-up in up to 87% of patients using Goldmann
      perimetry and up to 82% of patients using Humphrey perimetry. The visual status
      improved significantly throughout the follow-up period and the final visual
      outcome was excellent or good in 83% of patients.

PMID- 9614528
TI  - Questionnaire-based survey on the importance of quality of life measures in
      ophthalmic practice.
AB  - PURPOSE: To assess the awareness of the existence of quality of life (QOL)
      instruments and their perceived relative merit in the management of various eye
      conditions among ophthalmologists in the United Kingdom. METHODS: A self
      administered questionnaire was circulated among various grades of
      ophthalmologists attending a major UK ophthalmology conference. The respondents
      were asked to rank from a list in order of importance various tests of visual
      function in different ophthalmic conditions. RESULTS: Distance and near visual
      acuity were consistently rated high with mean ranks lower than 4.0. Contrast
      sensitivity and reading speed were consistently rated as low in importance with
      mean ranks ranging from 4 to 5.8. QOL instruments were deemed to be of some
      importance in the management of cataract and to a lesser extent in the management
      of age-related macular degeneration. Only 2 respondents of 36 could name either a
      generic or a vision-specific QOL instrument. CONCLUSION: UK ophthalmologists
      appear to be unfamiliar with QOL measures, despite the fact that in health
      economics they have become the standard means of assessing the results of health
      care interventions and of prioritizing funding. Notwithstanding the evolution of
      a variety of tests for the assessment of visual function, ophthalmologists still
      rely primarily on distance and, to a lesser extent, near visual acuity to plan
      their patient management. It is important to identify those tests of visual
      function that correlate best with the patient's ability to function in the seeing
      world, and to develop appropriate QOL instruments for use in ophthalmic
      disorders.

PMID- 9614527
TI  - The treatment of encapsulated trabeculectomy blebs in an out-patient setting
      using a needling technique and subconjunctival 5-fluorouracil injection.
AB  - PURPOSE: Encapsulation of the trabeculectomy bleb is a common cause of drainage
      failure in the early post-operative period. The primary management of bleb
      encapsulation has previously been to restart medical therapy, but recent advances
      in the technique of needle manipulation and the introduction of adjunctive 5
      fluorouracil (5-FU) have increased the popularity of early surgical bleb
      management. By reporting the results of bleb needling in a series of patients, we
      aim to illustrate its safety and efficacy. METHODS: We have reviewed a series of
      32 eyes in which needling and 5-FU injection was performed for bleb
      encapsulation, and analysed the results over a follow-up period of 10.7 +/- 2.9
      months. RESULTS: In 14 (43.7%) cases, primary needling was performed; in the
      other 18, needling was performed after conservative treatment had proved
      inadequate. The mean intraocular pressure (IOP) of the group decreased from 29.2
      +/- 10.5 mmHg prior to needling to 15.9 +/- 4.0 mmHg at the most recent
      attendance (paired t-test p = 1.3 X 10(-7), with all eyes having a final IOP
      measurement of 22 mmHg or less. Twenty-three (71.9%) of the cases maintained a
      target IOP of 18 mmHg or less without additional treatment; 5 (15.6%) were
      qualified successes with an untreated IOP between 19 and 21 mmHg. The remaining 4
      (12.5%) patients, whose IOPs ranged between 20 and 22 mmHg with one hypotensive
      agent, were considered needling failures. Choroidal detachment complicated the
      procedure in 2 cases; in each this resolved with conservative management and
      without long-term visual consequence. CONCLUSION: This technique is recommended
      as a safe and effective method of treating bleb encapsulation.

PMID- 9614529
TI  - Nutrition supplements and the eye.
AB  - PURPOSE: A review of the role of vitamins, minerals, carotenoids and essential
      fatty acids in relation to eye health. The mode of action may be directly on the
      eye or by promoting bodily health on which the eye depends. RESULTS: The lens and
      retina suffer oxidative damage and the anti-oxidant vitamins A, C and E are
      implicated as protective. Studies in man give indifferent support to the role of
      nutrition in the development of cataract. In the elderly, vitamin intake may be
      inadequate, so that a vitamin supplement may be reasonable. Zinc has a role in
      retinal metabolism and may be beneficial in macular degeneration. Selenium has an
      anti-oxidant role. Other minerals including copper have a less defined role.
      Carotenoids are concentrated at the macula and have an anti-oxidant role. A
      reduced risk of macular degeneration is found in relation to a high serum level.
      The essential fatty acid, gamma-linolenic acid (GLA), is useful in Sjogren's
      syndrome and may help in other dry eye conditions. Omega-3 fatty acids are
      important in retinal development and have a role in preventing cardiovascular
      disease. CONCLUSION: All persons should be encouraged to maintain healthy
      nutrition. Middle-aged and elderly patients may benefit from a supplement. An
      intake in excess of the recommended daily intake may be beneficial, but this is
      not proven. Further clinical trials are indicated to define the advisability of
      vitamin, mineral and other supplements. Dosages for recommended intake and for
      supplements are given.

PMID- 9614530
TI  - Loss of corneal Langerhans cells during storage in organ culture medium, Optisol
      and McCarey-Kaufman medium.
AB  - PURPOSE: This study compares the influence of different corneal preservation
      media on HLA-DR positive corneal Langerhans cells (LCs). METHODS: Using
      fluorescence-associated immunohistochemistry, corneal sections were stained for
      HLA-DR antigens after preserving corneal-scleral discs in three different storage
      media: organ culture medium. Optisol and McCarey-Kaufman medium. HLA-DR positive
      LCs were present in corneal epithelium and upper stroma of fresh corneas.
      RESULTS: A storage period of even 3 days had a significant influence on the
      number of HLA-DR positive corneal LCs. The number of LCs decreased at the limbus
      from 15.3 +/- 4.1 LCs/ 0.25 mm2 to 11.8 +/- 1.2 LCs/0.25 mm2 (p < 0.01) during
      preservation in McCarey-Kaufman medium, to 11.2 +/- 1.9 LCs/0.25 mm2 (p < 0.01)
      during preservation in organ culture medium and to 12.7 +/- 3.4 LCs/0.25 mm2 (p <
      0.01) during preservation in Optisol. A greater loss was detected after 7 days
      and we found a cell number of 1.6 +/- 1.1 LCs/0.25 mm2 (p < 0.001) after storage
      in organ culture medium and of 1.4 +/- 1.5 LCs/0.25 mm2 (p < 0.001) after storage
      in Optisol. The donor tissues entirely lacked HLA-DR positive LCs, regardless of
      the preservation medium used, when stored for up to 14 days. CONCLUSION: These
      results demonstrate that loss of HLA-DR antigens is mainly related to storage
      period and is independent of the type of preservation medium and preservation
      temperature.

PMID- 9614531
TI  - Post-keratoplasty endophthalmitis caused by Proteus mirabilis.
AB  - A diabetic patient who underwent a triple procedure (penetrating keratoplasty,
      cataract extraction and posterior chamber intraocular lens implantation),
      developed endophthalmitis caused by Proteus mirabilis. The source of infection
      was the infected donor cornea, which was imported from Sri Lanka. The organism
      was resistant to gentamicin, which was the only antibiotic present in the storage
      medium. On top of an aggressive antibiotic treatment regime (topical, systemic
      and intravitreal), exchange of the infected with a fresh corneal graft and pars
      plana vitrectomy were performed. The patient had a speedy recovery and the visual
      outcome was 20/40 two and a half years after the incident. To our knowledge, post
      keratoplasty endophthalmitis caused by P. mirabilis has never been reported in
      the literature. We report herein such a case with good visual outcome. Newer
      storage medium, such as Optisol GS, might have a role in preventing keratoplasty
      related infection.

PMID- 9614532
TI  - The effect of tear substitute and silicone oil on re-epithelisation of the
      cornea.
AB  - PURPOSE: An animal model study was conducted to compare the effects of recurrent
      applications of an artificial cellulosic tear substitute and silicone oil on
      corneal reepithelisation. METHODS: A controlled wound was inflicted to the
      corneas of two groups of rabbits; one group was treated with tear substitute (5
      eyes), while the other group received silicone oil (5 eyes). The left eye served
      as the control in both groups (10 eyes). The rate of re-epithelisation was
      measured at intervals of 6 h until complete wound closure was observed. After
      complete wound closure, the rabbits were killed and histological examinations
      were performed. RESULTS: The wounds of eyes treated with tear substitute closed
      at a statistically significant faster rate (at 24, 44, 80 h; p < 0.05) than those
      treated with silicone oil or the untreated eyes. At 48 h after re-epithelisation,
      the eyes treated with tear substitute presented a normal epithelium while the
      untreated and silicone-treated eyes presented an abnormally structured
      epithelium. CONCLUSION: This study demonstrates a favourable effect of tear
      substitute on corneal re-epithelisation in an animal model, in terms of both rate
      of re-epithelisation and histological aspects of the new epithelium.

PMID- 9614534
TI  - Retinal neovascularisation and posterior penetrating ocular injury.

PMID- 9614533
TI  - Haemorrhagic fever with renal syndrome caused by Puumala virus: evaluation of the
      risk for cataract formation.

PMID- 9614535
TI  - Allergic contact dermatitis reactions to corticosteroids in periorbital
      inflammation and conjunctivitis.

PMID- 9614536
TI  - Acute onset bilateral cataracts in an infant with vertically transmitted HIV with
      CMV retinitis despite treatment.

PMID- 9614537
TI  - Bilateral familial inferotemporal retinal dialyses.

PMID- 9614538
TI  - Spontaneous anterior capsular rupture in Alport syndrome.

PMID- 9614539
TI  - An uncommon presentation of the ocular ischaemia syndrome.

PMID- 9614540
TI  - Surgically induced keratoglobus in pellucid marginal degeneration.

PMID- 9614541
TI  - Benign schwannoma simulating a ciliary body melanoma.

PMID- 9614542
TI  - Central retinal artery occlusion due to rapidly expanding orbital lymphoma.

PMID- 9614543
TI  - Carbon deposits in the conjunctival fornices.

PMID- 9614544
TI  - Giant retinal tears after pars plana vitrectomy.

PMID- 9614545
TI  - CS gas ocular injury.

PMID- 9614546
TI  - Familial deafness associated with iris degeneration and glaucoma.

PMID- 9614547
TI  - Towards gene therapy for cystic fibrosis: a clinical progress report.

PMID- 9614548
TI  - Adenoviral TNF-alpha gene therapy and radiation damage tumor vasculature in a
      human malignant glioma xenograft.
AB  - We evaluated the antitumor effects of ionizing radiation and tumor necrosis
      factor-alpha (TNF-alpha) gene therapy in human malignant glioma (D54) xenografts.
      An adenoviral vector (Ad5) containing DNA sequences of the Egr-1 promoter was
      linked to a cDNA encoding the TNF-alpha gene (Ad. Egr-TNF). Athymic nude mice
      bearing D54 xenografts received intratumoral injections of Ad.Egr-TNF or the null
      vector (Ad.null), with and without fractionated radiation, 5 gray (Gy) per day
      for 6 days, a total dose of 30 Gy. Administration of Ad.Egr-TNF and 30 Gy
      resulted in complete tumor regression in 71% of xenografts compared with
      xenografts treated with radiation alone (7.4%, P = 0.006), Ad.Egr-TNF alone (0%,
      P = 0.012) or Ad.null with 30 Gy (0%, P = 0.002). Combined treatment with Ad.Egr
      TNF and 30 Gy significantly reduced mean fractional tumor volumes compared with
      radiation alone (P = 0.002), Ad.Egr-TNF alone (P = 0.002) and Ad.null plus 30 Gy
      (P = 0.018). Histopathologic analyses of glioma xenografts treated with Ad.Egr
      TNF and radiation revealed tumor vessel thrombosis by day 4 and necrosis by day
      7. Thrombosis was not observed in tumors treated with Ad.Egr-TNF alone and was
      significantly reduced in all other treatment groups. These studies suggest that
      in the D54 glioma xenograft model, the antitumor effects of combining radiation
      and Ad.Egr-TNF are mediated, in part, by the destruction of the tumor
      microvasculature.

PMID- 9614549
TI  - beta-Galactosidase staining following intracoronary infusion of cationic
      liposomes in the in vivo rabbit heart is produced by microinfarction rather than
      effective gene transfer: a cautionary tale.
AB  - The myocardium is a potential target for the expression of exogenous genes to
      treat inherited and acquired diseases. Although adenovirus-mediated gene transfer
      has resulted in high-level gene transfer in vivo via direct intramyocardial
      injection and via a percutaneous intra-arterial route, the time-course of gene
      expression is limited by host immune responses. It was the aim of this study to
      test whether cationic liposome-mediated gene transfer, which does not suffer from
      the aforementioned problems, was feasible in the adult rabbit myocardium via a
      percutaneous transluminal approach. Doses of plasmid DNA encoding lacZ from 200
      800 micrograms complexed to cationic liposomes resulted in X-gal conversion at
      day 3 with associated myocardial damage. We hypothesised that the damage was
      associated with macro-aggregates of cationic liposomes-DNA occluding the
      microcirculation. When such aggregates were excluded no X-gal conversion was seen
      in vivo. In order to show that X-gal conversion occurs in areas of infarction in
      the myocardium we caused closed chest infarction by deploying a platinum micro
      embolisation coil in the circumflex coronary artery. At day 3 X-gal conversion
      was observed in the territory supplied by the occluded artery. Thus,
      microinfarction causes the false positive appearance of gene transfer when using
      a lacZ reporter gene.

PMID- 9614550
TI  - Blunting of immune responses to adenoviral vectors in mouse liver and lung with
      CTLA4Ig.
AB  - Adenoviral vectors deleted of E1 are attractive vehicles for in vivo gene therapy
      because efficient gene transfer can be achieved. Immune responses to the vector
      and vector-transduced cells lead to destruction of target cells, inflammation and
      difficulties with vector readministration. Immune effectors have been identified
      as CD8+ cytotoxic T lymphocytes, which destroy vector-transduced cells, as well
      as B cells which secrete neutralizing antibodies and block repeated gene
      transfer. The central role of CD4+ T cells in the activation of both of these
      effector functions has focused immunosuppressive strategies towards blockade of
      costimulatory molecules. We describe in this study a strategy which aims to
      inhibit CD4+ T cell activation by transiently administering an inhibitor of the
      CD28/B7 pathway, ie CTLA4Lg, at the time an E1-deleted adenovirus is administered
      to liver or lung. In lung, CTLA4Ig treatment significantly blocked the formation
      of neutralizing antibodies, allowing efficient readministration of virus, whereas
      transgene expression was only moderately prolonged. In contrast, CTLA4Ig did not
      suppress neutralizing antibody formation in the context of liver gene therapy,
      but resulted in more stable gene expression. In vitro assays revealed suppression
      of T cell activation in either organ. This observation suggests that transient
      inhibition of the CD28/B7 pathway at the time of virus instillation can partially
      interfere with both arms of the immune response to adenovirus-mediated gene
      transfer circumventing the need for chronic immune suppression.

PMID- 9614551
TI  - Expression pattern of CD2 locus control region containing retroviral vectors in
      hemopoietic cells in vitro and in vivo.
AB  - We introduced the locus control region (LCR) of the human CD2 gene in eight
      different ways into retroviral constructs containing the human adenosine
      deaminase (hADA) gene. Two of these constructs were tested in transgenic mice.
      Neither expressed hADA in any examined tissue, nor did control vectors without
      the LCR insert. Amphotropic retrovirus vector producer cell clones were isolated
      and analyzed for provirus integrity and vector titer. Three constructs yielded
      recombined proviruses in 20-100% of transduced clones, whereas the other five
      constructs always rendered viruses that remained stable upon replication and gave
      vector titers comparable to the control lacking an LCR. Human ADA-deficient T
      cells and murine fibroblasts transduced with these recombinant viruses showed
      considerable hADA expression levels that were, however, not significantly
      different from those of cells transduced with the control vector lacking an LCR
      insert. Furthermore, no difference in hADA expression levels could be detected in
      spleen, thymus and bone marrow of long-term repopulated mice that had received
      bone marrow cells transduced with either the control vector or one of two
      different CD2-LCR containing vectors. In conclusion, the CD2-LCR does not
      alleviate the expression block for recombinant retroviruses in the germ line and
      does not enhance the LTR-driven expression in T cells.

PMID- 9614552
TI  - Induction of apoptosis in the rheumatoid synovium by Fas ligand gene transfer.
AB  - We have recently reported that local administration of anti-Fas monoclonal
      antibody (MAb) in human T cell leukemia virus type 1 (HTLV-1) carrying mice
      improved arthritis due to the induction of apoptosis. This finding strongly
      indicated the beneficial therapeutic effect of Fas-mediated apoptosis in
      rheumatoid arthritis (RA). To establish further the therapeutic effect of Fas
      mediated apoptosis on RA taking into consideration safety and practicality, we
      investigated the effect of cells transfected with human Fas ligand (hFasL) gene
      on proliferating human rheumatoid synovium engrafted in severe combined
      immunodeficiency (SCID-RA) mice. The hFasL transfectants exhibited cytotoxic
      activity against RA synoviocytes via the Fas/FasL system in vitro.
      Histopathological and immunohistochemical studies showed that local injection of
      irradiated-hFasL transfectants eliminated synoviocytes and mononuclear cells in
      engrafted human rheumatoid synovium of SCID-RA mice. Furthermore, in situ nick
      and labeling analysis confirmed that the cells in engrafted synovium frequently
      underwent apoptosis by irradiated-hFasL transfectants. Our results clearly
      demonstrated that hFasL transfectants induced apoptosis by cell-to-cell
      interaction via the Fas/FasL system. Thus, ex vivo gene transfer of FasL may
      represent a novel therapeutic strategy for RA.

PMID- 9614553
TI  - Monitoring adenoviral p53 transduction efficiency by yeast functional assay.
AB  - Monitoring the transduction efficiency is of paramount importance in gene
      therapy. To monitor adenovirus-mediated wild-type p53 gene transfer, we have used
      a quantitative assay which tests the ability of human p53 to activate
      transcription in yeast. Selective amplification of cellular and viral p53
      transcripts followed by quantitative assessment of mutant p53 content with the
      assay permits measurement of the wild-type p53 transduction efficiency into SF
      188, U251MG and HUG31 glioblastoma cells. One reverse transcription primer tracks
      the wild-type/mutant ratio of endogenous p53 mRNA (P2), and the other the wild
      type/mutant ratio of both endogenous and exogenous p53 mRNA (P1). Following
      infection of cell lines homozygous for mutant p53, the apparent transduction
      efficiency calculated (tau 0 = [P1-P2]/[1 + P2]) correlated with the level of p21
      expression. Transduction efficiency in heterozygous wild-type/mutant HUG31 cells
      increased linearly with multiplicity of infection (MOI) for tau 0 values between
      0.5 and 5.9, and admixture of normal cell-derived RNA produced only a modest
      reduction in tau 0 value, in keeping with theoretical predictions. These results
      suggest that the yeast p53 functional assay may be a useful tool for monitoring
      p53 gene therapy.

PMID- 9614554
TI  - Effects of bronchopulmonary inflammation induced by pseudomonas aeruginosa on
      adenovirus-mediated gene transfer to airway epithelial cells in mice.
AB  - Cystic fibrosis (CF) patients have endobronchial inflammation caused by infection
      with mucoid Pseudomonas aeruginosa. Since adenovirus vectors are being studied
      for gene therapy for CF, we sought to determine whether bronchopulmonary
      inflammation would influence adenovirus-mediated gene transfer. We hypothesized
      that bronchopulmonary inflammation in mice inoculated with mucoid P. aeruginosa
      would be associated with a decrease in the efficacy of adenovirus-mediated gene
      transfer. Agarose beads embedded with mucoid P. aeruginosa (6 x 10(4) c.f.u. per
      mouse) were inoculated transtracheally into C57BL/6 mice. Control mice received
      sterile agarose beads. Ten days after inoculation with agarose beads, recombinant
      adenovirus containing the beta-galactosidase reporter gene (Ad2/beta Gal-2) was
      administered intranasally (1.1 x 10(9) IU per mouse), and mice were killed 3 days
      later. The extent of inflammation, determined by neutrophil numbers in
      bronchoalveolar lavage fluid and by areal lung inflammation, was significantly
      greater in mice inoculated with P. aeruginosa-laden agarose beads and Ad2/beta
      Gal-2 compared with controls. Mice that had received Pseudomonas-laden agarose
      beads and Ad2/beta Gal-2 had significantly fewer (P < 0.015) airway epithelial
      cells transduced (4.1 +/- 0.9%) compared with mice that received sterile agarose
      beads and Ad2/beta Gal-2 (9.4 +/- 1.4%). These results indicate that the efficacy
      of adenovirus-mediated gene transfer is reduced in Pseudomonas-induced
      bronchopulmonary inflammation.

PMID- 9614555
TI  - Adenovirus-mediated expression of an elastase-specific inhibitor (elafin): a
      comparison of different promoters.
AB  - This report describes the design and construction of three recombinant
      adenoviruses of serotype 5 (Ad5) expressing elafin (EL), also called elastase
      specific inhibitor. Three promoters were chosen to drive the synthesis of elafin:
      the small (380 bp) human cytomegalovirus promoter (HCMV), the Ad2 major late
      promoter (MLP) and the mouse cytomegalovirus (MCMV) promoter. Human alveolar
      epithelial cells (A549), as well as rat and human primary pulmonary fibroblasts
      were infected with Ad5-HCMV-EL, Ad5-MLP-EL, Ad5-MCMV-EL and with the control Ad5
      dl70/3. The MCMV promoter was the most efficient promoter in all cells studied.
      MLP was the least efficient promoter Intermediate between MCMV and MLP was HCMV
      which was able to induce significant amounts of elafin, particularly in human
      A549 cells. When compared in vivo in rat lungs, results were similar; MCMV was
      the only promoter which induced significant amounts of elafin as assessed by
      Northern blot analysis and ELISA, even with a low dose of virus (3 x 10(8)
      p.f.u.). Our data indicate that the MCMV promoter is the promoter of choice for
      the strong induction of adenovirus-mediated transgenes in the lung and suggest
      its suitability both in rodent experimental models and in humans for
      investigative and therapeutic purposes.

PMID- 9614556
TI  - The levels of integrin alpha v beta 5 may predict the susceptibility to
      adenovirus-mediated gene transfer in human lung cancer cells.
AB  - Adenovirus mediated transfer of growth-inhibiting molecules, such as p53 shows
      promise as an effective method of suppressing the growth of cancer cells. As the
      basis for in vivo studies, we examined transfection efficiency using 15 human
      lung cancer cell lines that differ in their endogenous p53 status. When infected
      with an adenovirus expressing bacterial beta-galactosidase, the different cell
      lines showed different levels of beta-galactosidase activity. We found a
      correlation between the level of integrin alpha v beta 5, which is thought to be
      an adherence receptor for adenoviruses, and the expression level of the
      transferred gene, suggesting that gene expression is largely dependent on the
      infection efficiency. Growth inhibition was induced in all cell lines tested
      following infection with an adenovirus containing p53, regardless of the genetic
      status of their endogenous p53 provided a sufficient amount of p53 protein was
      expressed. Our results (1) confirm that the examination of the susceptibility of
      target cancer cells to an adenovirus is important when considering performing
      adenovirus-mediated gene transfer and for evaluating its therapeutic effects; and
      (2) suggest that the quantification of integrin alpha v beta 5 may be a good way
      of predicting the susceptibility of cells to adenoviral vectors.

PMID- 9614557
TI  - Adenovirus-mediated dystrophin minigene transfer improves muscle strength in
      adult dystrophic (MDX) mice.
AB  - Duchenne muscular dystrophy (DMD) and murine X-linked muscular dystrophy (mdx)
      are both due to absence of the subsarcolemmal protein dystrophin. Recombinant
      adenovirus vectors (AdV) are considered a promising means for delivering a
      functional dystrophin gene to muscle. However, the usefulness of AdV for this
      purpose is limited by vector toxicity as well as immune-mediated elimination of
      infected fibers. In addition, studies to date of AdV-mediated dystrophin gene
      transfer have either failed to examine effects on muscle strength or been
      performed in immunologically immature neonatal animals with little baseline
      abnormality of force-generating capacity. In the present study, AdV-mediated
      dystrophin gene transfer was performed in adult mdx mice with pre-existent
      dystrophic pathology and muscle weakness. The main findings are as follows: (1)
      acute myofiber toxicity and gene transfer efficiency are both AdV dose-dependent,
      such that the therapeutic margin of safety is fairly narrow; (2)
      immunosuppressive therapy (FK506) prevents immune-mediated elimination of
      dystrophin-positive fibers but not the dose-dependent toxic effects; (3) at the
      optimal vector dosage and with effective immunosuppression, AdV-mediated
      dystrophin minigene transfer is capable of alleviating the loss of force
      generating capacity as well as histopathological evidence of disease progression
      normally seen in adult mdx muscles over a 2-month period. These findings have
      important implications for the eventual application of AdV-mediated dystrophin
      gene transfer in DMD patients.

PMID- 9614558
TI  - Time-dependent maturation of cationic liposome-DNA complex for serum resistance.
AB  - Following our previous finding that increasing charge ratio (+/-) can overcome
      the serum sensitivity of cationic liposome-DNA complex, in the present studies we
      report that serum sensitivity of cationic liposome-DNA complex could also be
      overcome by prolonging the incubation time of the complex. Such time-dependent
      maturation of the complex was cationic lipid-dependent; complexes containing
      monovalent cationic lipids, eg DC-chol, DOTAP and lipofectin, matured with time,
      but those containing multivalent lipid, eg lipofectamine, do not. High charge
      ratio high concentration and high temperature accelerated the process of
      maturation. The serum sensitivity of cellular uptake of DNA was also dependent on
      the incubation time. The matured cationic liposome-DNA complexes are homogeneous
      particles with a mean diameter of 170 to 400 nm, depending on the cationic lipid
      in the complex.

PMID- 9614559
TI  - In vitro and in vivo antisense-mediated growth inhibition of a mammary
      adenocarcinoma from MMTV-neu transgenic mice.
AB  - Oncogene-bearing transgenic mice develop various kinds of tumors depending on
      both the regulatory sequences and the specific oncogene used. These mice not only
      help to clarify the pathogenetic pathways leading to tumor formation, but can
      also be useful as models to test novel therapeutic strategies, including gene
      therapy. We have previously reported the establishment of an MMTV-neu (ErbB-2)
      transgenic mouse lineage, in which 100% of females develop breast tumors with
      many features similar to their human counterparts; these tumors are due to the
      over-expression of the activated rat neu oncogene in the mammary gland. From one
      such mouse we established a cell line of mammary adenocarcinoma named MG1361. We
      report here that the growth of this cell line can be inhibited in vitro and in
      vivo by transfection of a plasmid vector carrying an antisense anti-neu
      construct. This inhibitory effect is specific, as it is related to the expression
      of the antisense transgene (determined by RT-PCR), and to a reduction in neu mRNA
      and protein, as determined by Northern and Western blot analyses. Moreover,
      inoculation of cells carrying the antisense or the control vector in nude mice
      demonstrated that the morphological and biochemical effects elicited by the
      antisense construct resulted in a significantly slower rate of in vivo growth of
      tumor xenografts. Finally, significant mammary tumor growth inhibition was
      obtained after liposome-mediated direct inoculation of the same antisense vector
      in tumors spontaneously arising in MMTV-neu mice. Taken together, these findings
      suggest that targeting neu expression by an integrated large anti-neu antisense
      segment affects the in vivo growth of these tumors.

PMID- 9614560
TI  - Differentiation-specific enhancer activity in transduced keratinocytes: a model
      for epidermal gene therapy.
AB  - HaCaT cells, a spontaneously immortalised, nontumorigenic keratinocyte line, were
      used as a more amenable model than primary keratinocytes for ex vivo-mediated
      gene transfer. These cells were transduced with retroviral vectors containing the
      factor IX cDNA under the control of a cytomegaloviral (CMV) promoter/enhancer
      alone or as hybrids with either the human papilloma virus-16 (HPV-16), keratin 14
      (hK14) or keratin 5 (hK5) regulatory elements. Unlike primary keratinocytes,
      HaCaT cells tolerated transduction and G418 selection well. The HPV-16 and hK5
      hybrid constructs were disproportionately more active in primary keratinocytes
      than in the basal-like HaCaT cells. After skin grafting to athymic mice,
      transduced HaCaT cells differentiated to form a stratified epidermis that
      remained viable for at least 99 days in some mice. Factor IX in plasma of mice
      grafted with vectors containing the HPV-16 and hK5 elements was two- to three
      fold higher than with vectors containing the CMV promoter alone. These results
      are consistent with the expected up-regulation in differentiated suprabasal cells
      by the HPV-16 and hK5 elements. Enhancers may be useful in specifically targeting
      the differentiated layer of the epidermis or achieving higher levels of gene
      expression after transplantation.

PMID- 9614561
TI  - Feasibility of multidrug resistance (MDR-1) gene transfer in patients undergoing
      high-dose therapy and peripheral blood stem cell transplantation for lymphoma.
AB  - We have performed a pilot study of MDR-1 gene transfer in patients receiving CD34
      selected peripheral blood stem cell (PBSC) transplant for lymphoma. To ensure
      minimum engraftment thresholds and facilitate CD34 purification, mobilisation of
      > 2 x 10(6) CD34 cells/kg was a condition for recruitment. Of 11 patients
      counselled for study entry, only five achieved this target in a single apheresis.
      In three consenting patients, purified CD34 cells were exposed to A12M1 MDR-1
      retroviral supernatant for 6 h, cryopreserved then thawed and readministered
      following ablative chemotherapy. No delay in engraftment was observed, although
      one patient received additional back-up cells. Gene transfer was demonstrated by
      polymerase chain reaction (PCR) for vector-derived MDR-1 cDNA sequence in all
      cases. Analysis of peripheral blood and bone marrow cells after transplant has,
      however, shown no evidence of in vivo gene transfer with a follow-up of 12, 15
      and 18 months. The effect of MDR-1 substrate drugs has not yet been tested as all
      patients remain in clinical and radiological remission of their lymphoma. These
      results confirm the difficulty of achieving in vivo gene transfer in human
      haemopoietic cells and indicate major logistical constraints in PBSC mobilisation
      in patients with relapsed and resistant disease in whom initial studies are
      appropriate.

PMID- 9614562
TI  - Chloroquine and amphipathic peptide helices show synergistic transfection in
      vitro.
AB  - A pH-responsive peptide fragment modelled on the influenza virus haemagglutinin
      (INF7-SGSC) can promote the transfectional activity of poly(L)-lysine (pLL)/DNA
      complexes against 293 cells. Chloroquine also promotes transfection, but the
      combination of INF7-SGSC and chloroquine gives an increased, synergistic,
      transfectional activity. This was unexpected since the supposed modes of action
      of these two agents are expected to be incompatible. Microinjection of pLL/DNA
      complexes into the cytoplasm of Xenopus oocytes produced greater gene expression
      than microinjection of free DNA, possibly reflecting nuclear-homing or protection
      from degradation by cytoplasmic nucleases. However, pretreatment of complexes
      with INF7-SGSC (but not chloroquine) before cytoplasmic microinjection promoted
      gene expression still further. When pLL/DNA complexes were injected directly into
      the nucleus, INF7-SGSC again increased gene expression. The mechanism of post
      endosomal action of INF7-SGSC is unknown, but could reflect its polyanionic
      nature, possibly enhancing intranuclear dissociation of the complexes. Whatever
      the mechanism, it appears that INF7-SGSC mediates two effects-one probably
      endosomal and the second post-endosomal, the latter showing a synergistic
      transfection interaction with chloroquine.

PMID- 9614563
TI  - Semliki Forest virus-based DNA expression vector: transient protein production
      followed by cell death.
AB  - We have constructed a novel DNA expression vector based on Semliki Forest virus
      (SFV). SFV produces non-structural proteins (nsPs) which replicate genomic RNA
      and amplify the mRNA encoding the structural proteins of SFV. A recombinant cDNA
      genome of SFV, in which the SFV structural genes were replaced by a polylinker
      cassette to allow for insertion of heterologous DNA, was placed under the control
      of a cytomegalovirus immediate-early enhancer/promoter with a polyadenylation
      signal. Transfection of mammalian cells with this SFV-based plasmid vector, pSFV3
      CMV-lacZ-pA, resulted in transient high-level expression of a beta-galactosidase
      reporter gene. The expression level of beta-galactosidase from pSFV3-CMVlacZ-pA
      was more than 20-fold higher than that obtained from the plasmid with deleted
      nsPs genes, pSFV3A5976-lacZ, demonstrating that the nsPs genes were essential for
      the high level of expression. Substantial beta-galactosidase activity was
      detected in the medium of pSFV3-CMV-lacZ-pA-transfected cells, suggesting that
      the overproduction of beta-galactosidase caused cell death and release of the
      protein into the medium. We have demonstrated a high-level expression of the
      exogenous beta-galactosidase gene from pSFV3-CMV-lacZ-pA constructed using an SFV
      replication system.

PMID- 9614564
TI  - Superior cytostatic activity of the ganciclovir elaidic acid ester due to the
      prolonged intracellular retention of ganciclovir anabolites in herpes simplex
      virus type 1 thymidine kinase gene-transfected tumor cells.
AB  - Ganciclovir (GCV) and its lipophilic elaidic acid ester prodrug E-GCV were
      evaluated for their antiherpetic, cytostatic and metabolic properties, E-GCV
      proved exquisitely inhibitory to the replication of herpes simplex virus type 1
      (HSV-1) and HSV-2 in cell cultures (50% effective concentration (EC50): 0.002
      microM). It was five- to 10-fold more effective than its parent drug GCV. E-GCV
      was at least 2000-fold more cytostatic to HSV-1 or HSV-2 thymidine kinase (tk)
      gene-transfected mammary carcinoma FM3A tk-/HSVtk+ tumor cells than to the
      corresponding nontransfected tumor cells. The cytostatic activity of E-GCV to the
      HSVtk gene-transfected tumor cells was far superior to that of GCV. Metabolic
      studies revealed that both GCV and E-GCV were converted to the mono-, di- and tri
      phosphate derivatives of GCV to a markedly higher extent in FM3Atk-/HSV-1 tk+
      cells than in wild-type FM3A/0 cells. Strikingly, mono-, di- and tri-phosphate
      metabolites of GCV were retained for a substantially longer time in E-GCV-treated
      cells (half-life approximately 50 h) than in GCV-treated cells (half-life
      approximately 20 h). The longer retention time of the GCV metabolites most likely
      explains why E-GCV is superior to GCV against herpes simplex virus replication
      and HSVtk gene-transfected tumor cell proliferation. Taking into account the
      marked stability of E-GCV in human plasma and its much higher lipophilicity than
      GCV, E-GCV should be considered as an effective lipophilic prodrug of GCV with a
      markedly enhanced cytostatic activity in HSVtk gene-transfected tumor cells
      compared with parental ganciclovir. Its usefulness in the combined
      gene/chemotherapy of HSVtk gene-transfected tumors should be further pursued.

PMID- 9614565
TI  - Impact of a new generation of gene transfer markers on gene therapy.

PMID- 9614567
TI  - Selective astrocytic transgene expression in vitro and in vivo from the GFAP
      promoter in a HSV RL1 null mutant vector--potential glioblastoma targeting.
AB  - Due to the lack of any effective therapy, novel approaches are currently being
      explored for the treatment of primary brain tumours. It has previously been
      demonstrated that variants of HSV-1 which are deleted in the RL1 gene and fail to
      produce the virulence factor ICP34.5 are potential candidates for tumour therapy.
      The RL1 variant 1716 replicates selectively within tumour cells and has the
      potential to deliver a therapeutic or tumour killing gene directly to the site of
      tumour growth. As many intracerebral tumours are glial and predominantly
      astrocytic in origin, we have evaluated the ability of 1716 to deliver a reporter
      gene specifically to astrocytes in vivo and in vitro using a 2.2 kb fragment
      which controls expression of the glial fibrillary acidic protein (GFAP), an
      astrocyte specific protein. Two 1716 variants, 1774 and 1775, were constructed
      which contain the GFAP-promoter element linked to the E. coli beta-galactosidase
      gene, inserted into the HSV-1 UL43 and US5 loci, respectively. In primary
      cultures, human primary tumour cell lines and established tumour cell lines in
      vitro, 1774 and 1775 gave high levels of expression of beta-galactosidase
      specifically in astrocytes. In vivo following intracerebral inoculation, both
      viruses demonstrated high levels of beta-galactosidase expression predominantly
      in astrocytes. These results indicate that the GFAP promoter element could be
      used for efficient and selective transgene delivery to human gliomas.

PMID- 9614566
TI  - Effects of macrophage depletion and anti-CD40 ligand on transgene expression and
      redosing with recombinant adenovirus.
AB  - The anti-CD40 ligand antibody MR-1, and macrophage-depleting liposomes were
      tested for their ability as transient immunosuppressive agents to: (1) prolong
      transgene expression; and (2) permit redosing after recombinant adenovirus
      infusion of mice. To test for effect on transgene duration, mice were infused
      with recombinant adenovirus coding for human factor IX (AdFIX), and plasma FIX
      levels monitored over time. Treatment with either agent significantly prolonged
      transgene expression. Persistence was accompanied by inhibition of anti
      adenovirus (anti-Ad) IgG, and decreased IL-10 and IFN-gamma production from
      splenic lymphocytes re-exposed to virus particles in vitro. To test for effect on
      redosing, mice were given a primary infusion of recombinant adenovirus coding for
      bacterial beta-galactosidase (Ad beta gal), followed by secondary and tertiary
      infusions of AdFIX on days 24 and 63. Mice that had received MR-1 had low to
      undetectable anti-Ad on day 24, and efficient transduction occurred. Furthermore,
      FIX levels endured in these mice, with 40% retention of FIX on day 63, in
      contrast to rapid loss in naive controls. On day 63, the continuance of
      negligible anti-Ad levels correlated with successful tertiary transduction. These
      results suggest that both macrophage depletion and CD40 ligand blockade inhibit
      immune responses to recombinant adenovirus to slow decline of transgene
      expression, while only CD40 ligand blockade inhibits anti-Ad antibody generation
      sufficiently to allow redosing to the liver.

PMID- 9614568
TI  - Severe hepatic dysfunction after adenovirus-mediated transfer of the herpes
      simplex virus thymidine kinase gene and ganciclovir administration.
AB  - The use of so-called 'suicide' genes to activate prodrugs has been effective in
      animal models for several solid tumor types and is now in phase I and II clinical
      trials. We have exploited adenovirus vectors (Ad) for transfer and expression of
      the herpes simplex virus thymidine kinase (HSVtk) gene to render rat colorectal
      liver metastases sensitive to the anti-herpetic agent ganciclovir (GCV). The
      efficacy and toxicity of this enzyme-prodrug combination were tested after in
      situ transduction of rat colorectal tumor cells and after intraportal
      administration of the vector Ad.CMV.TK. Our results demonstrate the validity of
      the approach but reveal that hepatic expression of HSVtk, both in tumor bearing
      and in tumor-free rats, provokes severe liver dysfunction and mortality upon GCV
      administration. These data show, that in contrast to the common assumption,
      normally non-mitotic tissues too, can be affected by adenovirus-mediated HSVtk
      transfer and subsequent GCV treatment. Given the hepatotropic nature of
      systemically administered adenovirus type 2- and 5-derived vectors, it will be
      essential to monitor liver functions of patients included in all gene therapy
      trials involving adenoviral vectors with the HSVtk gene.

PMID- 9614569
TI  - Persistent gene expression in rat liver in vivo by repetitive transfections using
      HVJ-liposome.
AB  - Most viral vectors are highly immunogenic and are of limited use for somatic gene
      therapy that requires repetitive administrations. We have developed a highly
      efficient gene transduction procedure useful for repetitive transfections using
      liposome containing hemagglutinating virus of Japan (HVJ-liposome). The
      Escherichia coli beta-galactosidase (beta-gal) gene was embodied in HVJ-liposome,
      and introduced directly into the caudal lobe of rat liver that was transiently
      isolated from a systemic circulation. A 116 kDa beta-gal protein was detected in
      transfected rat liver tissues by Western blot analysis and it was expressed in
      more than two-thirds of the liver by histological staining. It was found that the
      transfection efficiency was not affected by repetitive transfections. In support
      of these findings, antibody response to HVJ-liposome detected in the rat sera was
      weak and transient. Furthermore, cytotoxic T lymphocytes were not elicited
      against autologous rat hepatocytes that were transfected in vivo using HVJ
      liposome. Thus, our results demonstrate that the isolation of a target liver from
      systemic circulation and the direct administration of foreign genes using HVJ
      liposomes are useful for high gene transduction and persistent gene expression in
      the liver.

PMID- 9614570
TI  - Adenovirus vectors for gene transduction into mobilized blood CD34+ cells.
AB  - Mobilized blood CD34+ cells from cancer patients were ex vivo infected by a
      recombinant adenovirus vector carrying an alkaline phosphatase gene, whose
      expression is evaluable by flow cytometry. A mean of 40% CD34+ cells were
      infected by the vector, with high levels of expression of the transgene. Among
      attempts to improve infection efficiency by manipulating culture conditions, only
      reinfection by the same vector achieved a 10% increase of transgene expression.
      Transduced CD34+ cells were induced to differentiate along the myeloid and the
      dendritic lineage, and in either case AP+ cells were detectable among the
      differentiated cell population. We conclude that adenovirus vectors may be useful
      tools for gene transduction into mobilized blood CD34+ cells, particularly for
      those applications in which high transgene expression for limited periods of time
      is required.

PMID- 9614571
TI  - Complete correction of acid alpha-glucosidase deficiency in Pompe disease
      fibroblasts in vitro, and lysosomally targeted expression in neonatal rat cardiac
      and skeletal muscle.
AB  - The enzyme acid alpha-glucosidase catalyzes the breakdown of lysosomal glycogen.
      Absence of this enzyme results in infantile Pompe disease, characterized by
      hypertrophic cardiomyopathy, skeletal muscle weakness and fatal heart failure by
      2 years of age. We have examined the possibility of gene replacement therapy for
      this disease, by constructing an E1-deleted recombinant adenovirus encoding human
      acid alpha-glucosidase (Ad-GAA). The dose-response in fibroblasts from patients
      with Pompe disease transduced with this vector is linear over the range tested
      (one to 2000 plaque forming units (p.f.u.) of Ad-GAA per cell), and acid alpha
      glucosidase activity comparable to that of normal fibroblasts is achieved at 100
      p.f.u. per cell. Targeting of the recombinant protein to the lysosomal
      compartment was confirmed by immunocytochemistry. In vivo expression was examined
      by injecting Ad-GAA into newborn rats; intracardiac administration produced 10
      times the normal level of acid alpha-glucosidase activity in whole heart lysates,
      while a hind-limb i.m. injection increased activity in that muscle to six times
      the normal level. Western blotting of these tissues defected species at 76 kDa
      consistent with the size of processed lysosomal enzyme, and levels of expression
      as high as 1.0 mg recombinant protein per gram of tissue wet weight were
      produced. These data demonstrate high-level, lysosomal expression of recombinant
      acid alpha-glucosidase in treated target tissues and support the feasibility of
      gene replacement strategies for Pompe disease.

PMID- 9614572
TI  - Vaccination with IL-12 gene-modified autologous melanoma cells: preclinical
      results and a first clinical phase I study.
AB  - Cytokine gene transfer into tumor cells has been shown to mediate tumor
      regression and antimetastatic effects in several animal models via
      immunomodulation. Therefore, clinical protocols have been developed to treat
      cancer patients with cytokine gene-modified tumor cells. We inserted the genes
      coding for the p35 and p40 chain of interleukin-12 (IL-12) in two independent
      eukaryotic expression vectors and transduced melanoma cells of 15 different
      primary tumor cultures with both plasmids by a ballistic gene transfer approach.
      Secreted IL-12 demonstrated strong bioactivity by inducing interferon-gamma
      release from peripheral blood lymphocytes upon coculture with cell culture
      supernatants after IL-12 gene transfer which could at least partly be blocked by
      IL-12-specific antisera. Further enrichment of transduced tumor cells by magnetic
      separation directly after gene transfer increased cytokine secretion from a mean
      of 119 pg in the unsorted to 507 pg IL-12 (24 h/10(8) cells) in the magnetically
      enriched cell fraction. Irradiation of these cells led to a further elevation of
      secreted IL-12 (mean 987 pg). Elevated IL-12 levels were detected over 7 days
      after irradiation in vitro. In a subsequent first clinical phase I study six
      patients with metastatic melanoma were vaccinated with autologous, interleukin-12
      gene-modified tumor cells. Melanoma cells were expanded in vitro from surgically
      removed metastases, transduced by ballistic gene transfer, irradiated and were
      then injected subcutaneously (s.c.) at weekly intervals. Clinically, there was no
      major toxicity except for mild fever. All patients completed more than four s.c.
      vaccinations over 6 weeks and were eligible for immunological evaluation. Post
      vaccination, peripheral mononuclear cells were found to contain an increased
      number of tumor-reactive proliferative as well as cytolytic cells as determined
      by a limiting dilution analysis in two patients. Two patients developed DTH
      reactivity against autologous melanoma cells and one had a minor clinical
      response. Biopsies taken from that patient's metastases revealed a heavy
      infiltration of CD4+ and CD8+ T lymphocytes. In conclusion, vaccination induced
      immunological changes even in a group of advanced, terminally ill patients. These
      changes can be interpreted as an increased antitumor immune response.

PMID- 9614573
TI  - Drug inducible transgene expression in brain using a herpes simplex virus vector.
AB  - The ability to regulate transgene expression is likely to be important in the use
      of gene transfer to treat diseases of the central nervous system (CNS). In order
      to achieve regulatable gene expression we created a replication-incompetent
      genomic herpes simplex vector containing a RU486-inducible transactivator and a
      lacZ reporter gene under transcriptional control of a minimal promoter. Reporter
      gene expression from the vector was regulated by administration of RU486 in vitro
      and in vivo. In cell culture half maximal expression was achieved with 10(-8) M
      RU486, and maximal expression was achieved by 24 h. Following stereotactic
      inoculation of the vector into rat hippocampus, expression was increased 150-fold
      by i.p. administration of RU486. This demonstrates that the RU486 system
      functions as a tight on/off switch for regulating expression of a transgene
      delivered to the brain via an HSV vector.

PMID- 9614574
TI  - Major effects of TPO delivered by a single injection of a recombinant adenovirus
      on prevention of septicemia and anemia associated with myelosuppression in mice:
      risk of sustained expression inducing myelofibrosis due to immunosuppression.
AB  - Adenoviral vectors may be useful tools to deliver a cytokine in vivo. A single
      intravenous injection of an adenovirus vector containing the human thrombopoietin
      (TPO) cDNA (AdRSVhuTPO) was able to induce a thrombocytosis for more than 6 weeks
      in SCID mice, associated with a megakaryocyte (MK) hyperplasia in different
      organs. A marrow and spleen fibrosis was observed at 6 weeks. In immunocompetent
      mice, a single AdRSVhuTPO injection led to a moderate and transient
      thrombocytosis without myelofibrosis. To evaluate the usefulness of TPO for the
      prevention of secondary side-effects during an aplastic period, mice were
      subjected to a myeloablative regimen 7 days after the intravenous AdRSVhuTPO
      injection. In this setting, TPO prevented mortality by accelerating hematological
      recovery. Survival was essentially related to an improvement in the leukopenia
      since all control mice died from septicemia. However, the effects of TPO may be
      potentiated by the release of inflammatory cytokines following the adenovirus
      infection; AdRSV beta galactosidase injected-mice had higher numbers of BFU-E and
      CFU-GM in the marrow than PBS-injected mice. Myelosuppression induced transient
      immunosuppression responsible for a sustained expression and elevation of
      platelet numbers for at least 5 months. These results further suggest that TPO
      may be an effective therapy in diminishing hematological complications related to
      myeloablative regimens, but emphasize that immunosuppression secondary to
      myelosuppression may lead to sustained expression associated with a risk of
      thrombosis and myelofibrosis when delivered by adenovirus vectors.

PMID- 9614575
TI  - Regional 'pro-drug' gene therapy: intravenous administration of an adenoviral
      vector expressing the E. coli cytosine deaminase gene and systemic administration
      of 5-fluorocytosine suppresses growth of hepatic metastasis of colon carcinoma.
AB  - Direct administration of an adenoviral vector expressing the cytosine deaminase
      gene (AdCMV.CD) to tumors of colon carcinoma cells, with concomitant systemic
      administration of 5-fluorocytosine (5FC), results in local production of 5
      fluorouracil (5FU) and suppression of tumor growth. Based on the demonstration
      that in vivo adenovirus-mediated gene transfer to intrahepatic tumors is
      relatively inefficient compared with in vivo gene transfer to hepatocytes, we
      developed a 'regional' prodrug strategy using in vivo Ad-mediated CD gene
      transfer to normal liver, permitting hepatocytes to convert 5FC into 5FU to treat
      local metastasis effectively in a 'trans' fashion. To show that hepatocytes can
      generate and export sufficient 5FU to achieve this goal, primary rat hepatocytes
      were exposed to AdCMV.CD and 5FC. Evaluation of the supernatants by
      spectrophotometry and by HPLC demonstrated significant conversion of 5FC into
      5FU. When supernatants of hepatocytes exposed to AdCMV.CD and 5FC were
      transferred to cultures of CT26 mouse colon carcinoma cells, the CT26 viability
      was reduced by 80%. To show that this regional AdCMV.CD/5FC prodrug strategy can
      suppress tumor growth in vivo, a model of metastatic colon carcinoma was
      established by injecting CT26 cells into the left lobe of the liver of syngeneic
      Balb/c mice. The next day, AdCMV.CD was transferred to hepatocytes by intravenous
      administration, and 5FC treatment was started the following day. Evaluation of
      tumor growth after 15 days showed marked suppression of tumor growth in AdCMV.CD-
      and 5FC- treated animals compared to control groups (P < 0.007). We conclude that
      primary hepatocytes are capable of converting 5FC into 5FU and exporting
      sufficient amounts of 5FU to the local milieu to suppress the growth of liver
      metastases of colon carcinoma cells.

PMID- 9614576
TI  - Myosin regulatory elements as vectors for gene transfer by intramuscular
      injection.
AB  - Intramuscular injection of plasmid constructs promises to be an effective way of
      carrying out gene therapy for muscle disorders as well as using muscle as an in
      vivo expression system for disorders that involve the gene product being secreted
      into the bloodstream. The effectiveness of this method depends on the design of
      the cassette used for the expression of the cDNA of the introduced gene. We
      tested the levels of expression achieved by a number of muscle-specific promoters
      and a myosin light chain enhancer when spliced to the reporter gene
      chloramphenicol acetyltransferase (CAT), in vitro and in vivo by injection into
      fast and slow muscles of the mouse. The results show that the highest levels of
      expression are achieved by a combination of a truncated myosin heavy chain
      promoter and the enhancer, and that a whole range of expression levels is
      obtained with the other combinations tested. The data show that a cassette based
      on these elements should provide efficient vectors for the introduction and
      expression of genes following intramuscular injection of naked DNA.

PMID- 9614577
TI  - A chimeric fusion protein containing transforming growth factor-alpha mediates
      gene transfer via binding to the EGF receptor.
AB  - Fusion proteins engineered to incorporate distinct functions which co-operate in
      mediating the cell-type specific uptake and intracellular delivery of DNA present
      an attractive approach for the development of self-assembling vector systems for
      targeted gene transfer. Here we have chosen the EGF receptor overexpressed in
      many human tumors of epithelial origin as a target for a novel modular fusion
      protein. We have fused a cDNA fragment of the human EGF receptor ligand TGF-alpha
      to sequences encoding the translocation domain of Pseudomonas exotoxin A as an
      endosome escape activity, and the DNA-binding domain of the yeast GAL4
      transcription factor. Upon bacterial expression, this TEG fusion protein
      displayed specific binding to EGF receptors. Complexes of the chimeric protein
      and plasmid DNA carrying a luciferase reporter gene, after condensation with poly
      L-lysine resulted in an up to 150-fold increase in reporter gene expression in
      EGF receptor expressing cells in comparison to poly-L-lysine-DNA complexes alone.
      While in COS-1 cells no additional endosome escape activity was required, in A431
      cells gene delivery was dependent on the simultaneous presence of the endosome
      destabilizing reagent chloroquine indicating that cell-type specific factors such
      as different intracellular routing of protein-DNA complexes greatly influence
      transfection efficiency.

PMID- 9614578
TI  - Baculovirus-mediated gene transfer in the presence of human serum or blood
      facilitated by inhibition of the complement system.
AB  - Baculovirus vectors are efficient tools for gene transfer into hepatocytes in
      vitro. However, gene transfer is strongly reduced in the presence of native sera,
      providing an explanation for the failure of direct application of the virus in
      vivo. In this study, we define the role of the complement (C) system (C) as a
      major cause for baculovirus inactivation in human serum. Baculoviruses most
      likely activate the classical pathway of the C system and assembly of very late C
      components is required for inactivation of the vector. We demonstrate the
      survival of baculovirus vectors in human serum through treatment with a
      functional blocking antibody against C component 5. Inactivation of baculovirus
      in human plasma and whole blood was prevented by treatment with cobra venom
      factor. The data reveal various interactions of baculovirus vectors with the C
      system and will lead to facilitation of baculovirus-mediated gene transfer into
      hepatocytes in vivo by protection of the vector from C inactivation.

PMID- 9614579
TI  - Systemic action of human growth hormone following adenovirus-mediated gene
      transfer to rat submandibular glands.
AB  - We have previously suggested that although salivary glands function in an
      exocrine manner they might none the less offer a useful way to deliver
      therapeutic proteins systemically. As a direct functional test of this
      hypothesis, we constructed a recombinant adenovirus (AdCMVhGH) encoding human
      growth hormone (hGH) and then studied the biological action of hGH produced
      following transfer of the hGH gene to rat submandibular glands. At 48 h following
      infusion of AdCMVhGH into these glands via cannulation of the main excretory
      duct, serum levels of hGH were approximately 16 ng/ml and rat insulin-like growth
      factor-1 was elevated approximately 25%. Moreover, serum chemistry profiles of
      rats subjected to in vivo gene transfer displayed alterations in the
      BUN:creatinine ratio and triglyceride levels presumably reflecting the anabolic
      actions of the hGH. These results provide the first demonstration of systemic
      biological action from a transgene product secreted in an endocrine fashion from
      the salivary glands.

PMID- 9614580
TI  - Lipofection of cultured mouse muscle cells: a direct comparison of Lipofectamine
      and DOSPER.
AB  - Cationic lipid-DNA complexes (lipoplexes) have been widely used as gene transfer
      vectors which avoid the adverse immunogenicity and potential for viraemia of
      viral vectors. With the long-term aim of gene transfer into skeletal muscle in
      vivo, we describe a direct in vitro comparison of two commercially available
      cationic lipid formulations, Lipofectamine and DOSPER. Optimisation of
      transfection was performed in the C2C12 mouse muscle cell line, before further
      studies in primary mouse myoblasts and C2C12 myotubes. Reporter gene constructs
      expressing either E. coli beta-galactosidase or green fluorescent protein (GFP)
      were used in order to evaluate transfection efficiency by histochemical staining
      or FACS analysis, respectively. Both lipid formulations were able to promote
      efficient, reproducible gene transfer in C2C12 cells, and to transfect primary
      mouse myoblast cultures successfully. However, DOSPER exhibited the important
      advantage of being able to transfect cells in the presence of serum of both
      bovine and murine origin. This feature allowed increased cell survival during in
      vitro transfections, and may be advantageous for direct in vivo gene transfer
      efficacy.

PMID- 9614581
TI  - Retroviral gene transfer to the liver in vivo during tri-iodothyronine induced
      hyperplasia.
AB  - The liver is an important target organ for gene therapy but its mitotic
      quiescence makes it resistant to integrative gene transfer. Retrovirus-based
      vectors integrate into liver cells in vivo but require the liver to be primed
      before transduction; experimentally a 70% hepatectomy is commonly used to
      stimulate regeneration, rendering the liver susceptible to transduction during
      the resulting wave of cell proliferation. Our aim was to develop a clinically
      acceptable method of inducing hepatocyte replication before in vivo retroviral
      gene transfer which is both simple and effective. We have used the physiological
      hormone tri-iodothyronine (T3) to stimulate hepatocyte replication. A single dose
      of T3 (400 micrograms/100 g bw) was given subcutaneously to euthyroid rats. This
      produced a labelling index of 31.7% in the hepatocyte population without
      histological or biochemical evidence of preceding liver damage. Following T3
      administration the rat livers were transfected in vivo with an amphotropic
      retrovirus, TELCeB/AF-7 which encodes the beta-galactosidase reporter gene
      together with a nuclear localisation signal. Transgene expression was noted only
      within the liver where 1.3% of hepatocytes expressed the beta-galactosidase
      enzyme. This compared to 5.2% of hepatocytes transduced following a 70%
      hepatectomy, and 0.02% in animals receiving neither T3 nor partial hepatic
      resection before transduction. T3 administration is a simple way to prime the
      liver before in vivo retroviral vector-based gene transfer.

PMID- 9614582
TI  - Rapid analysis and efficient selection of human transduced primitive
      hematopoietic cells using the humanized S65T green fluorescent protein.
AB  - We have developed an efficient and rapid method to analyze transduction in human
      hematopoietic cells and to select them. We constructed two retroviral vectors
      using the recombinant humanized S65T green fluorescent protein (rHGFP) gene.
      Transduced cells appeared with specific green fluorescence on microscopy or
      fluorescence-activated cell sorting (FACS) analysis. The rHGFP gene was placed
      under the control of two different retroviral promotors (LTR) in the LGSN vector
      and in the SF-GFP vector. Amphotropic retroviruses were tested on NIH/3T3
      fibroblasts or human hematopoietic (K562, TF-1) cell lines. Then CD34+ cells
      isolated from cord blood were infected three times after a 48-h prestimulation
      with IL-3, IL-6, SCF or with IL-3, IL-6, SCF, GM-CSF, Flt3-L and TPO. After 6
      days of expansion, a similar number of total CD34(+)-derived cells, CD34+ cells
      and CFC was obtained in non-transduced and transduced cells, demonstrating the
      absence of toxicity of the GFP. A transduction up to 46% in total CD34(+)-derived
      cells and 21% of CD34+ cells was shown by FACS analysis. These results were
      confirmed by fluorescence of colonies in methyl-cellulose (up to 36% of CFU-GM
      and up to 25% of BFU-E). The FACS sorting of GFP cells led to 83-100% of GFP
      positive colonies after 2 weeks of methyl-cellulose culture. Moreover, a mean
      gene transfer efficiency of 8% was also demonstrated in longterm culture
      initiating cells (LTC-IC). This rapid and efficient method represents a
      substantial improvement to monitor gene transfer and retroviral expression of
      various vectors in characterized human hematopoietic cells.

PMID- 9614584
TI  - Wounds from civilian and military centerfire rifles.
AB  - This article explores the differences between rimfire and centerfire rifles and
      the differences in ammunition used. Permanent and temporary cavity wound tracks
      are explained. Radiographs, intermediary targets, and assault rifles are also
      discussed.

PMID- 9614583
TI  - FasL induces Fas/Apo1-mediated apoptosis in human embryonic kidney 293 cells
      routinely used to generate E1-deleted adenoviral vectors.
AB  - Human embryonic kidney 293 cells contain the E1 region of adenovirus type 5, and
      thus sustain, through transcomplementation, the production of recombinant E1
      deleted adenovirus vectors. During attempts to produce recombinant adenovirus
      expressing the apoptosis-inducing molecule Fas ligand (FasL) under the control of
      a very strong truncated major immediate-early human cytomegalovirus (MIEhCMV)
      promoter, we discovered that 293 cells were not surviving the initial
      cotransfection with a shuttle plasmid encoding the mouse FasL; and pJM17, a
      plasmid containing the genome of adenovirus type 5 with deletions in the E1-E3
      regions, in an unpackagable form. Investigation of the reason for massive cell
      death after cotransfection led us to determine that 293 cells express the FasL
      receptor. Fas-Apo1 (CD95), and respond with apoptosis to the cross-linking of Fas
      Apo1 with either IgM monoclonal antibodies or FasL. Therefore, we decided to
      generate adenoviral vectors expressing FasL, under the control of tissue-specific
      and/or-inducible promoter elements. Our findings can explain difficulties several
      groups have had in generating recombinant adenoviral vectors expressing FasL
      using 293 cells, as well as the lower titres reported.

PMID- 9614585
TI  - The scope of forensic radiology.
AB  - The use of x-ray in the solution of forensic problems commenced within days of
      Rontgen's discovery; indeed, most of the applications of radiology to the
      forensic sciences were accomplished or anticipated within the next two years. The
      scope of forensic radiology ranges widely and includes determination of identity,
      evaluation of injury and death, applications in both criminal and civil
      litigation and in administrative proceedings, detection of abuse, investigation
      of gunshot wounds, medical education and research. Newer modalities and
      techniques afford opportunity for the expansion of forensic radiology if problems
      of accessibility and cost can be resolved along with improvement in
      interdisciplinary cooperation and understanding.

PMID- 9614586
TI  - Forensic pathology. Pulmonary disease.
AB  - Certain conditions in cases with pulmonary pathology such as thrombosis and
      embolism, pregnancy, asthma, drug abuse, Sudden Infant Death Syndrome (SIDS) and
      occupational exposures are particularly likely to come under critical scrutiny
      and may form the basis of allegations of medical negligence, wrongful death or
      product liability. Pathologists may play an important role in the resolution of
      these legal claims through the proper performance, interpretation and reporting
      of their examinations. Pathologists can also assist in the legal process by
      explaining pathologic findings and their significance, correlating them with the
      clinical course and addressing issues of causation.

PMID- 9614587
TI  - Advances in forensic toxicology.
AB  - Over the last 15 years there have been many changes in the practice of forensic
      toxicology. One of the most noteworthy has been the recognition of the need for
      good laboratory practices in the forensic toxicology laboratory. This has
      resulted in the development of an accreditation program for laboratories.
      Increasingly, forensic toxicologists are asked to interpret results in driving
      under the influence of drug cases. These interpretations are also difficult
      because of the lack of data correlating blood (or plasma) concentrations with
      impairment. The development of newer immunoassays and hyphenated mass
      spectrometric techniques now allow the forensic toxicologist to assay a large
      number of drugs (both traditional and products of the biotechnology revolution)
      with increasing sensitivity. This article focuses on these changes and some of
      the challenges facing the forensic toxicologists of the 21st century.

PMID- 9614588
TI  - Developing medicolegal death investigator systems in forensic pathology.
AB  - As a result of recent national events involving high-profile murder cases,
      medicolegal death investigation has begun to slowly receive the attention it
      deserves. Despite continued local problems of financial support and political
      control, the development of regionalized centers of forensic excellence is
      gradually improving the access of rural and suburban areas to high-quality
      forensic science services. Recent efforts to improve the quality of lay death
      investigators through hiring practices, training, and certification promises to
      eventually provide more professionally qualified and experienced death
      investigators.

PMID- 9614589
TI  - Sudden natural death in infants and young children.
AB  - This discussion will highlight common natural causes of sudden unexpected death
      in "healthy" infants and young children. Methods employed to render these
      diagnoses will be reviewed. Natural causes of sudden death found more commonly in
      adolescents and young adults will not be discussed.

PMID- 9614590
TI  - Patterns of injury. Blunt and sharp.
AB  - The pathologist, by virtue of his or her observations and documentation of
      injuries with concomitant attempts to discern patterns of injury and correlate
      autopsy findings with investigative details, will often play an integral and
      primary role in the death investigation process. The information gleaned during
      this process, both pertinent positive and pertinent negative findings, however
      unimportant or insignificant they may seem during the initial examination, may
      potentially be of critical importance in answering future questions of a wide
      variety of interested parties, including law enforcement officials, prosecuting
      attorneys, defense attorneys, loved ones of the deceased, insurance companies,
      organ procurement officials, and news media. The pathologist, by virtue of his or
      her position in the process, is often the one best individual to collate and
      synthesize all findings of the process, both medical and investigative.

PMID- 9614591
TI  - Pitfalls in the interpretation of pediatric chest and airway radiographs.

PMID- 9614592
TI  - Health economic evaluations of antidepressants: a review.
AB  - In an era of constrained health care financing, clinicians are increasingly faced
      with considering the economic consequences in addition to the clinical outcomes
      associated with initiating a patient on antidepressant therapy. This has
      increased the demand for health economic studies comparing antidepressant use and
      associated health care expenditures in clinical practice. These health economics
      studies have used methods ranging from clinical trials to other types of analyses
      including prospective naturalistic trials or retrospective studies which may be
      less familiar to clinicians. Prospective and retrospective health economics
      studies performed in clinical practice complement the experience gained from
      clinical trials in assessing antidepressant use and economic outcomes in light of
      patient and provider behavior within the usual care environment of a complex
      health care system. Broadly considered, health economic studies of
      antidepressants have consistently found differences in clinical practice between
      the tricyclic antidepressants (TCAs) and the selective serotonin reuptake
      inhibitors (SSRIs) as well as among the SSRIs. These differences relate to the
      pattern and duration of antidepressant use as well as total direct health care
      expenditures. Future health economic research studies in clinical practice should
      focus on the economic consequences of long-term antidepressant use as well as the
      impact of antidepressant use on indirect costs such as productivity and
      absenteeism.

PMID- 9614593
TI  - Preliminary evidence for a beneficial effect of low-frequency, repetitive
      transcranial magnetic stimulation in patients with major depression and
      schizophrenia.
AB  - OBJECTIVE: This study was designed to evaluate the potential efficacy of
      repetitive transcranial magnetic stimulation (rTMS) at low-frequency in patients
      with major depression and schizophrenia. EXPERIMENTAL DESIGN: We investigated the
      therapeutic effect of a course of 10 rTMS sessions in 14 subjects with major
      depression (MD) and 10 with schizophrenia. PRINCIPAL OBSERVATIONS: Seven of the
      depressed patients reported significant improvement in depressive symptomatology,
      and seven of the schizophrenic subjects reported amelioration of anxiety and
      restlessness. CONCLUSIONS: These preliminary results suggest that low-frequency
      rTMS may be beneficial mainly in MD and to some extent in schizophrenia, and
      support the need for controlled studies to further validate its therapeutic
      potential.

PMID- 9614594
TI  - Effectiveness of fluoxetine and doxepin in treatment of melancholia in depressed
      patients.
AB  - It has been suggested that serotonin reuptake inhibitors (SSRIs) may be less
      effective than tricyclic antidepressants (TCAs) in treatment of melancholic
      depression. We treated 36 depressed ambulatory patients with doxepin or
      fluoxetine in a double-blind, randomized 6-week trial with placebo run-in. Seven
      patients treated with doxepin and 13 patients treated with fluoxetine met
      diagnostic criteria for melancholic depression. Average daily dose was 169.4 +/-
      41.6 mg for doxepin and 36.8 +/- 18 mg for fluoxetine. We observed a 50% response
      rate in both treatment groups, using as outcome criterion reduction of Hamilton
      Depression Scale Score to less than 10. Regardless of how strict the definition
      of response, we found fluoxetine to be as effective as doxepin in our group of
      melancholic outpatients.

PMID- 9614595
TI  - Use of bupropion with SRIs and venlafaxine.
AB  - Because of reported efficacy of combining classes of antidepressants, 25 patients
      were treated with bupropion in combination with SRI's and venlafaxine. Fifteen
      patients inadequately responsive to monotherapy received combination treatment;
      ten patients without residual symptoms received adjunctive bupropion to treat SRI
      or venlafaxine-induced side effects. Fourteen subjects (56%) responded, 11 (44%)
      did not. Twelve of 15 subjects receiving combination treatment to boost the
      effects of monotherapy responded, while only 2 of 10 subjects receiving
      combination treatment for side effects responded. Combination therapy was well
      tolerated even by geriatric and "medically frail" patients.

PMID- 9614596
TI  - Age of first onset of bipolar disorder: demographic, family history, and
      psychosocial correlates.
AB  - The literature suggests that bipolar elders with early and late onset of the
      disorder present with different demographic, family history, and psychosocial
      profiles, which are less well characterized than those for elderly unipolar
      patients. In this cross-sectional clinical survey, we assessed subjects (n = 74)
      from the NIMH Clinical Research Center for the Study of Depression in Later Life
      at Duke University who had a consensus diagnosis of bipolar depression; the
      primary assessment instrument was the Duke Depression Evaluation Schedule. We
      found that bipolar subjects with later age of onset reported less family history
      of psychiatric problems, more comorbid vascular disease, and more instrumental
      and subjective social support. Stressful life events were more frequent among
      bipolar subjects with earlier age of depressive symptom onset. This study
      suggests that early-onset disorder may be characterized by a psychosocial
      component, whereas organic factors may be particularly important to late-onset
      bipolar disorder.

PMID- 9614597
TI  - Tolerability of oral loading of divalproex sodium in the treatment of acute
      mania.
AB  - OBJECTIVE: To conduct a pilot study on the safety and tolerability of a dosage
      strategy for divalproex sodium beginning with 30 mg/kg/day. It is hypothesized
      that loading at this level will reach therapeutic levels of valproate more
      quickly, which in turn will decrease the latency of the therapeutic effect.
      METHOD: We conducted a retrospective chart review of all acutely manic patients
      admitted to our facility over a 12-month period. Those inpatients treated with
      initial divalproex sodium dosages of 30 mg/kg/day for 2 days, followed by 20
      mg/kg/day thereafter, were then included in the study. The serum valproate levels
      and daily Brief Psychiatric Rating Scale (BPRS) scores were documented for each
      subject. Any adverse changes in daily vital signs, serum liver enzymes, and blood
      cell counts were noted as well. Nursing and physician notes were then reviewed
      for any observed or reported adverse effects. RESULTS: Twelve acutely manic
      inpatients were enrolled in the study. Three subjects did not complete the
      treatment and are not included in this analysis. The remaining nine subjects
      completed the treatment, had a mean decrease in BPRS scores of 33.3%, and were
      discharged at least in partial remission. Six subjects had serum valproate levels
      drawn within 48-72 h of the initial dose, with a mean valproate level of 93.5
      mcg/ml. All nine subjects tolerated the treatment reasonably well, with one
      subject reporting sedation, one reporting sedation and constipation, and one
      reporting nausea, emesis, and urinary frequency. A transient, asymptomatic
      decrease in white blood cell count and a low granulocyte count were also noted in
      one subject. CONCLUSION: A divalproex dosage strategy beginning with 30 mg/kg/day
      for 2 days, followed by 20 mg/kg/day thereafter, was reasonably well tolerated in
      this group of acutely manic patients, even with the concurrent use of other
      psychotropic medications. Blood levels of 56 to 124 mcg/ml were observed within 3
      days after initiating treatment.

PMID- 9614598
TI  - Cerebral response to pain in two depressed patients.

PMID- 9614599
TI  - Psychostimulant augmentation of second generation antidepressants: a case series.
AB  - OBJECTIVE: The authors attempted to treat Major Depressive Disorder (MDD)
      suboptimally responsive to one of the newer (second-generation) antidepressants
      by augmentation with a psychostimulant medication. METHOD: Seven cases of MDD
      showing a partial response to an adequate trial of a second generation
      antidepressant were augmented with a psychostimulant. RESULTS: A marked
      improvement in clinical symptoms of depression was noted in all cases, with
      particular improvement in apathy and feelings of fatigue. CONCLUSION:
      Psychostimulant augmentation of the newer generation antidepressants is a
      promising new strategy. Further controlled investigation is warranted to explore
      various aspect of this method.

PMID- 9614600
TI  - Reversal of atypical depression, sleepiness, and REM-sleep propensity in
      narcolepsy with bupropion.
AB  - We successfully treated a 46-year-old narcoleptic woman suffering from atypical
      depression with bupropion hydrochloride. Diagnostic evaluation revealed a Beck
      Depression Inventory (BDI) score of 24, a short nocturnal REM-sleep latency,
      subjective and objective sleepiness (mean sleep latency (MSL) = 1.8 minutes), and
      three sleep onset REM-sleep periods during the five nap multiple sleep latency
      test. Bupropion (100 mg t.i.d.) normalized her mood (BDI = 6), sleepiness (MSL =
      9.1 minutes), and REM-sleep propensity. Upon discontinuation of bupropion, these
      parameters reverted to pretreatment levels. This "activating" antidepressant's
      reversal of the sleepiness and REM-sleep propensity in narcolepsy may be due to
      blockade of dopamine or norepinephrine reuptake. Clinicians need to be alert to
      the fact that depression can mask the diagnosis of narcolepsy. Bupropion warrants
      further investigation as a treatment for narcolepsy in an open-label, double
      blind, placebo-controlled paradigm.

PMID- 9614601
TI  - Incorporation of quality-of-life considerations into intensive diabetes
      management protocols in adolescents.

PMID- 9614602
TI  - Pre-conception planning. The relationship's the thing.

PMID- 9614603
TI  - Why don't women with diabetes plan their pregnancies?
AB  - OBJECTIVE: To determine why women with diabetes generally do not plan their
      pregnancies, consequently entering their pregnancies with poor blood glucose
      control and greatly increasing the risk of birth defects in their infants.
      RESEARCH DESIGN AND METHODS: A population-based sample of 85 women with diabetes
      diagnosed before the index pregnancy were recruited within 6 months postpartum
      from 15 hospitals in the state of Washington. Women with planned and unplanned
      pregnancies were compared using qualitative and quantitative analysis of personal
      interviews, self-administered questionnaires, and medical record review. RESULTS:
      Although most women (79%) knew they should optimize their blood glucose levels
      before conception, fewer than half (41%) of their pregnancies were planned. Women
      with planned pregnancies had significantly higher income and more education; were
      more likely to have private health insurance, to see an endocrinologist before
      pregnancy, to be happily married, and to be Caucasian; and were less likely to
      use tobacco. Most unplanned pregnancies were not contraceptive failures, but may
      have been consciously or subconsciously intended. Women with planned pregnancies
      generally described an ongoing and positive relationship with their health care
      providers. Women who felt that their doctors discouraged pregnancy were more
      likely to have an unplanned pregnancy than were women who had been reassured they
      could have a healthy baby. CONCLUSIONS: Many women with diabetes still perceive
      negative messages about pregnancies and become pregnant without optimal planning.
      We believe there are many opportunities for increasing the proportion of women
      with diabetes who plan their pregnancies, particularly in the areas of
      prepregnancy information, support that women are given, and the quality of the
      relationships they experience within the health care system. It is crucial that
      couples be reassured that with pre-conception glucose control, almost all women
      with diabetes can have healthy babies.

PMID- 9614604
TI  - Patient choice in diabetes education curriculum. Nutritional versus standard
      content for type 2 diabetes.
AB  - OBJECTIVE: To examine the effects of patient choice between two education
      curriculums that emphasized either the standard or nutritional management of type
      2 diabetes on class attendance and other outcomes among a mostly Hispanic patient
      population. RESEARCH DESIGN AND METHODS: A total of 596 patients with type 2
      diabetes were randomly assigned to either a choice or no choice condition.
      Patients in the choice condition were allowed to choose their curriculum, while
      patients in the no choice condition were randomly assigned to one of the two
      curriculums. Outcomes were assessed at baseline and at a 6-month follow-up.
      RESULTS: When given a choice, patients chose the nutrition curriculum almost four
      times more frequently than the standard curriculum. Contrary to our hypothesis,
      however, patients who had a choice did not significantly increase their
      attendance rates or demonstrate improvements in other diabetes outcomes compared
      with patients who were randomly assigned to the two curriculums. Patients in the
      nutrition curriculum had significantly lower serum cholesterol at a 6-month
      follow-up, whereas patients in the standard curriculum had significant
      improvements in glycemic control. Of the randomized patients, 30% never attended
      any classes; the most frequently cited reasons for nonattendance were
      socioeconomic. Hispanic patients, however, were just as likely as non-Hispanic
      patients to attend classes and participate at the follow-up. Patients who
      attended all five classes of either curriculum significantly increased their
      diabetes knowledge, gained less weight, and reported improved physical
      functioning compared with patients who did not attend any classes. CONCLUSIONS:
      Although providing patients with a choice in curriculums at the introductory
      level did not improve outcomes, differential improvements were noted between
      patients who attended curriculums with different content emphasis. We suggest
      that diabetes education programs should provide the opportunity for long-term,
      repetitive contacts to expand on the modest gains achieved at the introductory
      level, as well as provide more options to match individual needs and interests
      and to address socioeconomic barriers to participation.

PMID- 9614605
TI  - Short-term effects of coping skills training as adjunct to intensive therapy in
      adolescents.
AB  - OBJECTIVE: Given the urgent need to develop effective programs that improve the
      ability for adolescents to achieve metabolic control equivalent to programs
      studied in the Diabetes. Control and Complications Trial, we have undertaken a
      clinical trial to determine if a behavioral intervention (coping skills training
      [CST]) combined with intensive diabetes management can improve metabolic control
      and quality of life in adolescents implementing intensive therapy regimens.
      RESEARCH DESIGN AND METHODS: A total of 65 youths between the ages of 13 and 20
      years, who elected to initiate intensive insulin therapy, were randomly assigned
      to one of two groups: the intensive management with CST group and the intensive
      management without CST group. CST consists of a series of small group efforts
      designed to teach adolescents the coping skills of social problem-solving, social
      skills training, cognitive behavior modification, and conflict resolution. Data
      were collected at pre-intervention and at 3 months following the use of the Self
      Efficacy for Diabetes scale, Children's Depression Inventory, Issues in Coping
      with IDDM scale, and the Diabetes Quality of Life: Youth scale. Clinical data
      (HbA1c, adverse effects) were collected monthly. RESULTS: The experimental and
      control groups were comparable on all measures at baseline. Results show that
      adolescents who received CST had lower HbA1c and better diabetes self-efficacy
      and were less upset about coping with diabetes than adolescents receiving
      intensive management alone. In addition, adolescents who received the CST found
      it easier to cope with diabetes and experienced less of a negative impact of
      diabetes on quality of life than those who did not receive CST. CONCLUSIONS: CST
      is useful in improving not only an adolescent's metabolic control, but also their
      quality of life. As more pediatric providers aim for improved control, in
      adolescents with diabetes, the addition of this behavioral intervention may be
      helpful in achieving metabolic and life goals.

PMID- 9614606
TI  - Personal and family factors associated with quality of life in adolescents with
      diabetes.
AB  - OBJECTIVE: Quality of life is an important criterion for assessing outcomes of
      treatment in chronic illness related to psychosocial well-being. The purpose of
      this study was to evaluate the factors that influence quality of life in
      adolescents with IDDM. RESEARCH DESIGN AND METHODS: Self-reports were obtained
      from 52 adolescents (age 13-20 years, mean 16.1 +/- 1.9 [mean +/- SD], diabetes
      duration 8.2 +/- 3.4 years, 49% female) using the following scales: Diabetes
      Quality of Life for Youths, Children's Depression Inventory, Issues in Coping
      with Diabetes, Diabetes Family Behavior Scale, Family Adaptability and Cohesion,
      Self-Efficacy for Diabetes, and the Adolescent Coping Orientation. Metabolic
      control was measured by HbA1c. RESULTS: Teenagers whose diabetes had the greater
      impact (R2 = 0.48) and were less satisfied (R2 = 0.45) felt that management was
      more difficult (r = 0.56) and that diabetes was more upsetting (r = 0.63). They
      also used fewer rebellion strategies for coping (r = -0.44), had lower diabetes
      self-efficacy (r = -0.36), and had more depressive symptoms (r = 0.61). Higher
      impact was also associated with higher family warmth and caring (r = -0.54) and
      lower family adaptability (r = -0.42). Teenagers who were more worried (R2 =
      0.37) about their diabetes felt that management was more difficult (r = 0.40) and
      that diabetes was more upsetting (r = 0.58), and they used less rebellion (r = 
      0.49) and more ventilation (r = 0.42) to cope, had lower diabetes (r = -0.40) and
      medical (r = -0.30) self-efficacy, were more depressed (r = 0.55), and their
      families were less warm and caring (r = -0.33). HbA1c levels were not associated
      with quality of life or any other psychosocial factors except in teenagers who
      perceived their families as providing more guidance and control. These teenagers
      had lower HbA1c values than those whose families were less involved. CONCLUSIONS:
      Even teenagers who are successfully achieving HbA1c goals of therapy may perceive
      diabetes as having a negative impact on their lives, be depressed, and find
      diabetes difficult to manage. Diabetes treatment teams need to pay equal
      attention to the psychosocial needs to the quiet, nonrebellious teen with well
      controlled diabetes from a supportive family as they do to the rebellious
      adolescent with poorly controlled diabetes.

PMID- 9614607
TI  - Metabolic control and quality-of-life self-assessment in adolescents with IDDM.
AB  - OBJECTIVE: To examine the relation between metabolic control and self-assessed
      quality of life in adolescents with IDDM. RESEARCH DESIGN AND METHODS: The
      Diabetes Quality of Life (DQOL) questionnaire for youths was given to 69 subjects
      with IDDM aged 10-20 years at the time of their outpatient visit. Subjects with
      IDDM of < 1 year's duration or with documented psychotic disorder or mental
      retardation were excluded. Metabolic control was assessed by the mean HbA1c
      during the preceding year (long-term), by a single HbA1c at the time of the visit
      (short-term), and by the number of acute events related to IDDM in the preceding
      year. RESULTS: The DQOL score correlated with mean HbA1c (beta = 6.13, R2 = 0.22,
      P = 0.0122) and single HbA1c (beta = 3.94, R2 = 0.18, P = 0.05). Self-health
      assessment was the best predictor of DQOL score (beta = -44.42, R2 = 0.45, P <
      0.0001). The Worries subscale score on DQOL correlated with the occurrence of
      acute events (beta = 6.97, R2 = 0.2, P = 0.006), but did not correlate with
      either HbA1c level. Correlations of mean HbA1c with the predictors were stronger
      than the correlations of single HbA1c with the same predictors. CONCLUSIONS:
      Metabolic control and quality of life are two important outcomes of IDDM care. In
      our study, adolescents in better metabolic control report better quality of life.
      Both components need to be addressed in developing successful diabetes treatment
      strategies for adolescents with IDDM.

PMID- 9614608
TI  - Well-being and symptoms in relation to insulin therapy in type 2 diabetes.
AB  - OBJECTIVE: To determine the influence of insulin therapy on physical symptoms,
      emotional and general well-being, and treatment satisfaction in patients with
      type 2 diabetes. RESEARCH DESIGN AND METHODS: A descriptive prospective 2-year
      cohort study was performed. The study population consisted of 272 eligible NIDDM
      patients of Dutch origin > or = 40 years of age who had a known diabetes duration
      > or = 3 months and who were treated with diet and/or oral hypoglycemic agents.
      Dependent variables in the logistic regression analysis were scores on the Type 2
      Diabetes Symptom Checklist, the Profile of Mood States, and questions regarding
      general well-being and treatment satisfaction. Potential determinants under study
      were age, sex, known diabetes duration, insulin dose, duration of insulin
      therapy, comorbidity, baseline and change in metabolic parameters and
      cardiovascular risk factors. RESULTS: A baseline and 2-year questionnaire were
      available for 157 patients (58%). During follow-up, 39 of them (24.8%) were
      treated with insulin. Initiation of insulin therapy was significantly associated
      with improved glycemic control (mean HbA1c 8.2 +/- 1.4 [SD] to 7.4 +/- 0.9%, P =
      0.001) and weight gain (BMI 27.1 +/- 3.9 to 28.6 +/- 4.3 kg/m2, P = 0.000). Of
      all symptom and well-being scores, only feelings of emotional fatigue worsened
      significantly, although modestly (0.4-1.7 on a scale of 0.0-10.0, P = 0.02).
      Although diabetes management with insulin was experienced as more demanding (P =
      0.04), treatment satisfaction scores were not adversely influenced (2.5-1.9, P =
      0.39). High insulin doses were significantly and independently associated with
      high symptom scores (total score, hypoglycemic score) and with low mood
      (displeasure score, anger, tension, emotional fatigue) and perceived state of
      health. CONCLUSIONS: Initiation of insulin therapy in type 2 diabetes improves
      glycemic control effectively, has little influence on physical and psychological
      well-being dimensions, and does not affect treatment satisfaction.

PMID- 9614609
TI  - Evidence that the age at diagnosis of IDDM is genetically determined.
AB  - OBJECTIVE: The aim of this study was to determine the impact of genetic or
      environmental factors on the age or time of onset of IDDM by studying pairs of
      twins and siblings concordant for the disease. RESEARCH DESIGN AND METHODS: From
      404 twin pairs referred to a diabetic twin study, we selected pairs concordant
      for IDDM: 1) 116 identical pairs with an index twin diagnosed diabetic under age
      60 years and 2) 12 identical and 12 nonidentical matched twin pairs. From 972
      families referred to a population-based diabetic family study, we selected
      sibling pairs with IDDM: 33 pairs with an index case diagnosed diabetic under age
      21 years. Twin and sibling pairs were analyzed for intraclass correlations for
      age and time of diagnosis. RESULTS: Of twins concordant for IDDM, the age at
      diagnosis correlated 1) in 116 identical pairs (R = 0.94; P < 0.000001) and 2)
      more closely in 12 identical twins (R = 0.96, P < 0.000001) than 12 nonidentical
      twins (R = 0.59, P = 0.046). Of 33 sibling pairs with IDDM, the age, but not the
      time, of diagnosis was correlated (R = 0.53, P = 0.0016). CONCLUSIONS:
      Correlations within pairs of twins and siblings for age, not time, at diagnosis
      suggest that much of the variability of the age at diagnosis of IDDM is
      genetically determined.

PMID- 9614610
TI  - Well-being and treatment satisfaction in older people with diabetes.
AB  - OBJECTIVE: To measure well-being and treatment satisfaction and their correlates
      in older people with diabetes. RESEARCH DESIGN AND METHODS: A postal survey was
      conducted of 1,000 diabetic patients aged > or = 60 years, representing 56% of
      the resident older diabetic population in an inner-city health district with a
      largely indigenous population of 230,000 people and a widely varied socioeconomic
      mix. Well-being and treatment satisfaction were measured with diabetes-specific
      instruments and correlated with patient data held in a central register. RESULTS:
      There was an 81% response. The general well-being scores (median [interquartile
      range]) for patients on diet alone, tablets, and insulin were 54 (44-60), 53 (42
      61), and 48 (35-56) (P < 0.001 comparing insulin with diet and tablets) compared
      with a scale maximum of 66. Treatment satisfaction scores were 35 (31-36), 35 (32
      36), and 34 (30-36) (P < 0.001 comparing insulin with diet and tablets), scale
      maximum 36. Mean HbA1c concentrations were 5.0 +/- 1.4% (for patients on diet
      alone), 5.8 +/- 1.6% (tablets), and 6.6 +/- 1.7% (insulin) (P < 0.001 for each
      difference). Neither well-being nor treatment satisfaction correlated with HbA1c.
      Insulin-treated patients were younger and had been diabetic longer than non
      insulin-treated patients; their well-being remained slightly, but significantly,
      lower when adjusted for age, sex, BMI, and diabetes duration, but treatment
      satisfaction was no longer significantly different. Women had lower well-being
      than men. CONCLUSIONS: It has proved possible to measure well-being and treatment
      satisfaction in a large community-based samples of older people with diabetes. At
      the level of glycemic control in this population, neither parameter correlated
      with HbA1c. The lower well-being in insulin-treated patients remained significant
      in multivariate analysis.

PMID- 9614611
TI  - High prevalence of diabetes in Bahrainis. Associations with ethnicity and raised
      plasma cholesterol.
AB  - OBJECTIVE: To determine prevalence of diabetes and associated risk factors in the
      population of Bahrain. RESEARCH DESIGN AND METHODS: A cross-sectional study of
      2,128 Bahrainis aged 40-69 years was conducted. RESULTS: Age-standardized
      prevalence of diabetes was 25% in Jaafari Arabs, 48% in Sunni Arabs, and 23% in
      Iranians. In multivariate analyses, positive family history of diabetes, low
      educational status, waist girth, plasma cholesterol, and, in women,
      postmenopausal status were independently associated with diabetes. Adjusting for
      these factors did not account for the difference in prevalence between Jaafari
      and Sunni Arabs. There was no association between diabetes and parental
      consanguinity. Mean plasma cholesterol was 0.5 mmol/l higher in diabetic than in
      normoglycemic participants, 0.5 mmol/l higher in Sunni than in Jaafari Arabs,
      and, excluding diabetic individuals, 0.2 mmol/l higher in those with a positive
      family history of diabetes than in those with a negative family history. Although
      28% of participants had BMI > or = 30 kg/m2, only 42% of these obese individuals
      rated themselves as overweight. In men, obesity was inversely related to physical
      activity at work. In women, obesity was associated with high parity and inversely
      associated with employment outside the home. CONCLUSIONS: The high rates of
      diabetes in Bahrain and other Arabian Peninsula populations appear to be part of
      a familial syndrome that includes raised plasma cholesterol levels. Risk is
      related to ethnic origin but not to parental consanguinity. Despite the high
      rates of diabetes, obesity is still perceived as a desirable attribute in this
      population.

PMID- 9614612
TI  - Identification and treatment of cystic fibrosis-related diabetes. A survey of
      current medical practice in the U.S.
AB  - OBJECTIVE: To describe physicians' attitudes and practices in screening for and
      treating abnormalities in glucose homeostasis in cystic fibrosis (CF) patients
      and to test the hypotheses that guidelines for screening for CF-related diabetes
      (CFRD) are not followed at most centers and that screening and treatment vary by
      the care provider's background. RESEARCH DESIGN AND METHODS: This cross-sectional
      survey included three groups of physicians: 1) 593 members of the Lawson Wilkins
      Pediatric Endocrine Society (LWPES), 2) 462 members of the pediatric assembly of
      the American Thoracic Society (ATS), and 3) 194 directors of cystic fibrosis
      centers (CFD). A mailed questionnaire was used for the survey. RESULTS: The
      overall response rate was 67%. Of these, 224 LWPES, 143 ATS, and 135 CFD
      physicians reported actively seeing CF patients. About two-thirds of CF
      physicians (ATS and CFD) reported routine screening for impaired glucose
      tolerance (IGT) in asymptomatic CF patients; a random glucose is most often used
      (60%), followed by HbA1c (50%), urine glucose (44%), fasting glucose (21%), and
      oral glucose tolerance test (2%). Only 40% of LWPES physicians reported
      intervening for stress-induced hyperglycemia, but 61% reported use of insulin for
      persistent IGT. Management of CFRD was similar for all groups; most physicians
      used insulin (91%). LWPES recommended more intensive glucose testing and
      nutritional guidelines than did ATS/CFD (P < 0.0001). LWPES reported less concern
      about risks of diabetes complications (P < 0.0001) and the importance of
      minimizing burdensome interventions (P < 0.01). All groups considered weight
      management a top priority. CONCLUSIONS: Screening for IGT is not routinely done
      in CF patients and screening tests vary. Greater agreement exists on methods of
      treating patients with persistent IGT or CFRD, although goals and aggressiveness
      of treatment vary with the provider's background. A consensus conference is
      recommended.

PMID- 9614613
TI  - Mapping genes for NIDDM. Design of the Finland-United States Investigation of
      NIDDM Genetics (FUSION) Study.
AB  - OBJECTIVE: To map and identify susceptibility genes for NIDDM and for the
      intermediate quantitative traits associated with NIDDM. RESEARCH DESIGN AND
      METHODS: We describe the methodology and sample of the Finland-United States
      Investigation of NIDDM Genetics (FUSION) study. The whole genome search approach
      is being applied in studies of several different ethnic groups to locate
      susceptibility genes for NIDDM. Detailed description of the study materials and
      designs of such studies are important, particularly when comparing the findings
      in these studies and when combining different data sets. RESULTS: Using a careful
      selection strategy, we have ascertained 495 families with confirmed NIDDM in at
      least two siblings and no history of IDDM among the first-degree relatives. These
      families were chosen from more than 22,000 NIDDM patients, representative of
      patients with NIDDM in the Finnish population. In a subset of families, a spouse
      and offspring were sampled, and they participated in a frequently sampled
      intravenous glucose tolerance test (FSIGT) analyzed with the Minimal Model. An
      FSIGT was completed successfully for at least two nondiabetic offspring in 156
      families with a confirmed nondiabetic spouse and no history of IDDM in first
      degree relatives. CONCLUSIONS: Our work demonstrates the feasibility of
      collecting a large number of affected sib-pair families with NIDDM to provide
      data that will enable a whole genome search approach, including linkage analysis.

PMID- 9614614
TI  - Prevalences of type 2 diabetes, the insulin resistance syndrome, and coronary
      heart disease in an elderly, biethnic population.
AB  - OBJECTIVE: To compare the prevalences of type 2 diabetes, the various
      cardiovascular risk factors encompassing the insulin resistance syndrome (IRS),
      and coronary heart disease (CHD) in elderly Hispanics compared with non-Hispanic
      whites. RESEARCH DESIGN AND METHODS: Elderly Hispanics (n = 414) and non-Hispanic
      whites (n = 469), randomly selected from the Medicare rolls of Bernalillo County
      (Albuquerque, NM; age > or = 65 years), underwent a home interview followed by an
      interview/examination by a nurse-practitioner, nurse, and nutritionist that
      included an evaluation of glucose tolerance. Prevalences of total and central
      obesity, dyslipidemia, hypertension, and microalbuminuria also were determined.
      History of myocardial infarction, recent angina, and/or coronary bypass graft,
      and electrocardiograms (ECGs) were used to document CHD. RESULTS: Elderly
      Hispanics had twice the prevalence of type 2 diabetes compared with non-Hispanic
      whites, but the prevalence of impaired glucose tolerance was not increased in
      Hispanics. Mean serum fasting and 2-h post-glucola insulin concentrations,
      fasting insulin resistance indexes, and HbA1c were higher in Hispanics. Hispanics
      were shorter, weighed less, and had more total body and central obesity. The
      higher prevalences of dyslipidemia in Hispanics could be explained by a higher
      prevalence of diabetes. The prevalences of hypertension and CHD were not
      different for the two ethnic groups. CONCLUSIONS: Elderly Hispanics had twice the
      prevalence of diabetes and higher prevalences of cardiovascular risk factors
      associated with IRS. Prevalences of hypertension and CHD were similar in the two
      ethnic groups.

PMID- 9614615
TI  - Clustering of cardiovascular risk factors in urban Asian Indians.
AB  - OBJECTIVE: To study the prevalence of cardiovascular risk factors in native urban
      Asian Indians and to look for the occurrence of clustering of these factors.
      RESEARCH DESIGN AND METHODS: The study included 953 subjects (532 men and 421
      women), aged > or = 40 years, selected from a population survey for diabetes,
      which was conducted in 1994 in Madras, Tamil Nadu, India. Measurements of
      anthropometry, blood pressure, plasma lipid profile, glucose tolerance, plasma
      insulin response, and electrocardiogram were made. Based on the normal ranges
      derived from the population study, abnormalities in anthropometric values, plasma
      lipids, and insulin values were determined. Age-adjusted prevalences of the
      abnormalities were calculated using data from a 1991 urban census in Madras. The
      expected prevalences of the abnormalities in isolation and in combinations were
      calculated and compared with the corresponding observed figures. RESULTS: The
      prevalences of risk factors were in the order of central adiposity > dyslipidemia
      > hyperinsulinemia (2-h) > glucose intolerance > obesity > hypertension. The age
      adjusted prevalence of coronary heart disease (CHD) was 3.9% (3.5% in men and
      4.5% in women, NS), and T wave inversion was seen in an additional 10.3%.
      Isolated prevalences of all factors, except hypertension, were in lower frequency
      than expected. Combinations of each risk factor with one or two more risk factors
      occurred more frequently (1.3-4 times) than expected by chance. Impaired glucose
      tolerance and dyslipidemia showed association with hyperinsulinemia, whereas
      hypertension did not show such an association. CONCLUSIONS: Clustering of the
      cardiovascular risk factors or the components of insulin resistance syndrome
      occurs in the native Asian Indian population. This finding under-scores the need
      for preventive aspects of metabolic disorders and CHD.

PMID- 9614616
TI  - Impact of a diabetes electronic management system on the care of patients seen in
      a subspecialty diabetes clinic.
AB  - OBJECTIVE: To compare the compliance with diabetes care performance indicators by
      diabetes specialists using a diabetes electronic management system (DEMS) and by
      those using the traditional paper medical record. RESEARCH DESIGN AND METHODS: A
      DEMS has been gradually introduced into our subspecialty practice for diabetes
      care. To assess the value of this DEMS as a disease management tool, we completed
      a retrospective review of the medical records of 82 randomly selected patients
      attending a subspecialty diabetes clinic (DC) during the first quarter of 1996.
      Eligible patients were defined by the suggested criteria from the American
      Diabetes Association Provider Recognition Program. During the first quarter of
      1996, approximately one half of the providers began using the DEMS for some but
      not all of their patient encounters. Neither abstractors nor providers were aware
      of the intent to examine performance in relationship to use of the DEMS. RESULTS:
      Several measures were positively influenced when providers used the DEMS. The
      number of foot examinations, the number of blood pressure readings, and a
      weighted criterion score were greater (P < 0.01) for providers using the DEMS.
      There was evidence, although not statistically significant, for lower mean
      diastolic blood pressures (P = 0.043) in patients and for number of glycated
      hemoglobins documented (P = 0.018) by users of the DEMS. CONCLUSIONS: Performance
      and documentation of the process of care for patients with diabetes in a
      subspecialty clinic are greater with the use of a DEMS than with the traditional
      paper record.

PMID- 9614617
TI  - Improvement of HbA1c and blood glucose stability in IDDM patients treated with
      lispro insulin analog in external pumps.
AB  - OBJECTIVE: To compare the efficacy of the short-acting insulin analog lispro (LP)
      with that of regular insulin in IDDM patients treated with an external pump.
      RESEARCH DESIGN AND METHODS: Thirty-nine IDDM patients (age, 39.4 +/- 1.5 years;
      sex ratio, 22M/17W; BMI, 24.4 +/- 0.4 kg/m2; diabetes duration, 22.5 +/- 1.6
      years) who were treated by external pump for 5.1 +/- 0.5 years were involved in
      an open-label, randomized, crossover multicenter study comparing two periods of 3
      months of continuous subcutaneous insulin infusion with LP or with Actrapid HM, U
      100 (ACT). Boluses were given 0-5 min (LP) or 20-30 min (ACT) before meals. Blood
      glucose (BG) was monitored before and after the three meals every day. RESULTS:
      The decrease in HbA1c was more pronounced with LP than with ACT (-0.62 +/- 0.13
      vs. -0.09 +/- 0.15%, P = 0.01). BG levels were lower with LP (7.93 +/- 0.15 vs.
      8.61 +/- 0.18 mmol/l, P < 0.0001), particularly postprandial BG levels (8.26 +/-
      0.19 vs. 9.90 +/- 0.20 mmol/l, P < 0.0001). Standard deviations of all the BG
      values (3.44 +/- 0.10 vs. 3.80 +/- 0.10 mmol/l, P = 0.0001) and of postprandial
      BG values (3.58 +/- 0.10 vs. 3.84 +/- 0.10 mmol/l. P < 0.02) were lower with LP.
      The rate of hypoglycemic events defined by BG < 3.0 mmol/l did not significantly
      differ between LP and ACT (7.03 +/- 0.94 vs. 7.94 +/- 0.88 per month,
      respectively), but the rate of occurrences of very low BG, defined as BG < 2.0
      mmol/l, were significantly reduced with LP (0.05 +/- 0.05 vs. 0.47 +/- 0.19 per
      month, P < 0.05). At the end of the study, all but two (95%) of the patients
      chose LP for the extension phase. CONCLUSIONS: When used in external pumps, LP
      provides better glycemic control and stability than regular insulin and does not
      increase the frequency of hypoglycemic episodes.

PMID- 9614618
TI  - Effects of sickle cell trait and hemoglobin C trait on determinations of HbA1c by
      an immunoassay method.
AB  - OBJECTIVE: A number of studies, including the Diabetes Control and Complications
      Trial (DCCT), have shown that good glycemic control, as assessed by GHb
      measurements, can reduce the chronic complications of diabetes. The National
      Glycohemoglobin Standardization Program (NGSP) was established to insure that GHb
      measurements by different methods were comparable and could be related to the
      candidate reference method used in the DCCT. The measurement of HbA1c in patients
      with Hb variants is one area not directly addressed by the NGSP. Therefore, we
      assessed the comparability of two DCCT-traceable methods in samples with Hb
      variants. RESEARCH DESIGN AND METHODS: Samples containing HbAA, HbAC, and HbAS
      were collected from diabetic and nondiabetic patients. HbA1c concentrations were
      measured by a high-performance liquid chromatography method (Bio-Rad Diamat) and
      an immunoassay that is suitable for use in a physician's office (Bayer DCA 2000).
      RESULTS: The two methods compared well for samples with HbAA and HbAS. However,
      for samples containing HbAC the immunoassay method showed relative positive
      biases of 8.4 and 10.4% at HbA1c levels of 7 and 9%, respectively, such that the
      two methods would not be judged comparable according to NGSP guidelines.
      CONCLUSIONS: The DCA 2000 HbA1c immunoassay method showed significant positive
      bias in patients with HbC trait. One possible clinical implication of this
      overestimation is overly rigorous glycemic control with a concomitant increase in
      hypoglycemia. This may be especially important in certain ethnic populations,
      such as African-Americans, who have a relatively high prevalence of HbC trait.

PMID- 9614619
TI  - Pramlintide, a synthetic analog of human amylin, improves the metabolic profile
      of patients with type 2 diabetes using insulin. The Pramlintide in Type 2
      Diabetes Group.
AB  - OBJECTIVE: To examine the effects of 4 weeks of subcutaneous administration of
      pramlintide, a synthetic analog of human amylin, on metabolic control in patients
      with type 2 diabetes using insulin. RESEARCH DESIGN AND METHODS: Serum
      fructosamine, HbA1c, and fasting plasma lipids were measured in 203 patients in a
      randomized double-blind placebo-controlled parallel-group multicenter trial using
      doses of 30 micrograms q.i.d., 60 micrograms t.i.d., and 60 micrograms q.i.d.
      RESULTS: Statistically significant reductions in serum fructosamine
      concentrations were observed in the pramlintide 30 micrograms q.i.d. group (17.5
      +/- 4.9 mumol/l, P = 0.029), the pramlintide 60 micrograms t.i.d. group (24.1 +/-
      4.9 mumol/l, P = 0.003), and the 60 micrograms q.i.d. group (22.6 +/- 4.1
      mumol/l, P = 0.001) compared with the placebo group (3.5 +/- 3.8 mumol/l). There
      were also statistically significant shifts in the proportion of patients with an
      abnormal serum fructosamine concentration at baseline that normalized at week 4
      within the pramlintide 60 micrograms t.i.d. group and the 60 micrograms q.i.d.
      group. Consistent with the fructosamine results, there were statistically
      significant reductions in HbA1c in the pramlintide 30 micrograms q.i.d. group
      (0.53 +/- 0.07%, P = 0.0447), the pramlintide 60 micrograms t.i.d. group (0.58 +/
      0.07%, P < 0.0217), and the pramlintide 60 micrograms q.i.d. group (0.51 +/-
      0.08%, P = 0.0242) compared with the placebo group (0.27 +/- 0.08%). Total
      cholesterol concentrations were also statistically significantly reduced in both
      the pramlintide 60 micrograms t.i.d. group (8.4 mg/dl, P < 0.01) and 60
      micrograms q.i.d. group (10.5 mg/dl, P < 0.01) compared with placebo (1.2 mg/dl).
      Body weight decreased in both of the pramlintide 60 micrograms groups, but the
      trend did not achieve statistical significance. The incidence of hypoglycemia was
      similar in all treatment groups. CONCLUSIONS: Reductions in serum fructosamine,
      plasma total and LDL cholesterol concentrations, and HbA1c support the hypothesis
      that pramlintide may improve metabolic control in patients with type 2 diabetes
      using insulin.

PMID- 9614620
TI  - Apolipoprotein E polymorphism and renal function in German type 1 and type 2
      diabetic patients.
AB  - OBJECTIVE: To examine the association of renal function in diabetic patients with
      apolipoprotein (apo) E polymorphism. RESEARCH DESIGN AND METHODS: Apo E
      genotypes, lipid and lipoprotein serum levels, creatinine clearance (CCr), and
      excretion of marker proteins were determined in German type 1 (IDDM; n = 162) and
      type 2 (NIDDM; n = 124) diabetic patients. Albumin and immunoglobulin (Ig) G are
      considered to reflect charge-size permselectivity of the glomerular capillary
      basement membrane, and increased alpha 1-microglobulin (MG) excretion indicates
      compromised reabsorptive capacity of the renal tubules. RESULTS: Patients with
      NIDDM had higher lipid levels and lower CCrs than patients with IDDM. In patients
      with IDDM, age- and sex-adjusted analysis of variance showed an association
      between apo E genotypes and CCr, and the Jonckheere-Terpstra test demonstrated a
      decreasing glomerular filtration rate in the following order of genotypes:
      epsilon 4 epsilon 4/epsilon 4 epsilon 3 > epsilon 3 epsilon 3 > epsilon 2 epsilon
      2/epsilon 2 epsilon 3. Multiple linear regression analyses revealed that in
      patients with IDDM, the epsilon 2 allele was a negative predictor of CCr and a
      positive predictor of urinary excretion of albumin, IgG and alpha 1-MG
      independent from HDL and LDL cholesterol, TG concentration, age, and sex.
      CONCLUSIONS: Apo E polymorphism influences serum lipoprotein levels in patients
      with IDDM and NIDDM. Apo E polymorphism may be a renal risk factor of clinical
      relevance in normolipidemic patients with IDDM.

PMID- 9614621
TI  - Plasma adrenomedullin levels in type 1 diabetes. Relationship with clinical
      parameters.
AB  - OBJECTIVE: To assess the relationship between plasma adrenomedullin (AM) levels
      and the presence of microvascular complications in type 1 diabetic patients.
      RESEARCH DESIGN AND METHODS: We measured plasma AM and cAMP levels in 103 type 1
      diabetic patients (46 without complications, 24 with retinopathy only, 14 with
      microalbuminuria but normal kidney function, and 19 with renal insufficiency) and
      41 matched healthy control subjects. RESULTS: Patients with renal insufficiency
      had higher levels of AM and cAMP than all other groups. Patients with only
      retinopathy showed a trend to have higher levels than patients without
      complications. There were no differences among all other groups. There was a
      significant correlation between AM and cAMP in the total diabetic group (rs =
      0.36, P < 0.001) but not in the control group. In multiple regression analysis,
      plasma AM demonstrated significant relationships with creatinine clearance (beta
      = -0.31, P = 0.004) and duration of the disease (beta = 0.28, P = 0.008).
      CONCLUSIONS: Plasma AM and cAMP are increased in type 1 diabetic patients with
      renal insufficiency. Creatinine clearance (CrClc) and duration of the disease are
      related to plasma AM levels in these patients.

PMID- 9614622
TI  - Carotid atherosclerosis in adolescents and young adults with IDDM. Relation to
      urinary endothelin, albumin, free cortisol, and other factors.
AB  - OBJECTIVE: To investigate 1) alterations of carotid intimal-plus-medial thickness
      (IMT) in subjects with IDDM and 2) the relation of IMT to indexes of diabetic
      angiopathy and to risk factors of atherosclerosis. RESEARCH DESIGN AND METHODS:
      IMT was assessed by ultrasound B-mode imaging in 39 subjects with IDDM (23 male,
      16 female young adults aged 17.5 +/- 5.2 years, diabetes duration 8.8 +/- 5.9)
      and in 22 control subjects (healthy siblings of the IDDM subjects) of comparable
      age. Urinary endothelin (UET1) and urinary free cortisol (UFC) were determined by
      radioammunoassay (RIA), urinary albumin by nephelometry, HbA1c by high
      performance liquid chromatography (HPLC), and plasma renin by immunoradiometric
      assay (IRMA). RESULTS: The IMT values were greater in IDDM subjects than in
      control subjects (0.49 +/- 0.1 mm, 0.44 +/- 0.09 mm, respectively; P = 0.048) and
      greater in IDDM male subjects than in control male subjects (0.52 +/- 0.09 and
      0.44 +/- 0.06 mm, respectively; P = 0.015), with no difference between IDDM and
      control female subjects. The IMT values were greater in diabetic male subjects
      than in female subjects (0.52 +/- 0.09 and 0.45 +/- 0.1 mm, respectively; P =
      0.017). In IDDM subjects, but not in control subjects, there was a positive
      correlation of IMT to urinary albumin (P = 0.008), systolic blood pressure (P =
      0.023), UET1 (P = 0.016), UFC (P = 0.002), and BMI (P = 0.021). Multiple
      regression analysis demonstrated that in IDDM subjects the variable that
      interacts independently with IMT was the BMI (P = 0.001). CONCLUSIONS: IMT, an
      index of atherosclerosis (macroangiopathy), is increased in IDDM subjects quite
      early (already in adolescence), and it is positively related to urinary albumin,
      UET1, blood pressure, and UFC.

PMID- 9614623
TI  - Elevated concentrations of soluble E-selectin and vascular cell adhesion molecule
      1 in NIDDM. Effect of intensive insulin treatment.
AB  - OBJECTIVE: To evaluate the effects of a 14-day intensive insulin therapy and
      short-term improvement of glycemic control on serum levels of soluble forms of
      adhesion molecules, i.e., intercellular adhesion molecule-1 (sICAM-1), vascular
      cell adhesion molecule-1 (sVCAM-1), and E-selectin (sE-selectin) in NIDDM
      patients with poor glycemic control. RESEARCH DESIGN AND METHODS: A total of 16
      NIDDM patients were compared with 23 healthy subjects (control group) and
      investigated before and after intensive insulin treatment. RESULTS: On day 0, sE
      selectin and sVCAM-1 levels were significantly higher in NIDDM patients than in
      nondiabetic control subjects (median 87, range 63-115; median 544, range 408-797
      vs. 58, 43-80; 443, 395-573 ng/ml, respectively) (P < 0.008 in both cases). On
      day 15, the fall in sE-selectin levels was significant (P < 0.0001) and at a
      lesser extent in sVCAM-1 levels (64, 48-85; 506, 417-678 ng/ml, respectively);
      these levels reached values that no longer differed from those of control
      subjects (P = 0.23 and 0.15, respectively). Moreover, the fall in sE-selectin was
      positively associated with the change in LDL cholesterol and the improvement of
      glycemia. CONCLUSIONS: In poorly controlled NIDDM patients, sE-selectin levels
      are increased and significantly fall to normal after short-term improvement of
      glycemic control. This suggests that assaying sE-selectin makes it possible to
      detect endothelium activation and to follow its reversal with euglycemia.

PMID- 9614624
TI  - Influence of interindividual variability of aldose reductase protein content on
      polyol-pathway metabolites and redox state in erythrocytes in diabetic patients.
AB  - OBJECTIVE: To clarify the influence of interindividual difference in the level of
      aldose reductase on the polyol pathway-related metabolism in diabetic patients.
      RESEARCH DESIGN AND METHODS: The enzyme protein content was determined by a two
      site enzyme-linked immunosorbent assay using monoclonal and polyclonal antibodies
      to recombinant human aldose reductase in erythrocytes from 35 diabetic patients
      and 11 healthy volunteers. Patients were stratified into two groups by the median
      of aldose reductase content, and the erythrocyte sorbitol level, the fructose
      level, and the lactate-to-pyruvate ratio were compared between the two groups. We
      also examined the correlation of the enzyme content with these metabolic
      parameters. RESULTS: The group of patients whose enzyme content was above the
      median showed a significant increase in the levels of sorbitol (34.7 +/- 4.9 vs.
      20.4 +/- 2.0 nmol/g Hb, P < 0.05) and fructose (99.8 +/- 17.2 vs. 45.9 +/- 4.6
      nmol/g Hb, P < 0.05), along with an elevated lactate-to-pyruvate ratio (28.6 +/-
      6.1 vs. 11.7 +/- 1.2, P < 0.05), compared with patients with low enzyme levels.
      The aldose reductase content in erythrocytes was well correlated with its
      activity, and there was a significant correlation between the enzyme content and
      the erythrocyte sorbitol (r = 0.58, P < 0.001) or fructose (r = 0.57, P < 0.001)
      levels as well as between the enzyme level and the lactate-to-pyruvate ratio (r =
      0.38, P < 0.05). CONCLUSIONS: These results suggest that the interindividual
      variability of aldose reductase content may contribute tangibly to the polyol
      pathway flux and cytoplasmic redox alteration in diabetic patients.

PMID- 9614625
TI  - Enhanced progression of urinary albumin excretion in IDDM during puberty.
AB  - OBJECTIVE: To determine whether the progression of urinary albumin excretion rate
      (AER) is higher during puberty than before or after this period. RESEARCH DESIGN
      AND METHODS: A prospective study was conducted in which normoalbuminuric
      prepubertal (n = 20), pubertal (n = 28), and postpubertal (n = 26) IDDM groups
      matched for diabetes duration and long-term metabolic control were followed for 3
      years. At 6-month intervals, 24-h urine collection was used to determine AER.
      RESULTS: AER increased significantly over a period of 3 years in the pubertal (P
      = 0.001) and postpubertal (P = 0.003) subjects but not in prepubertal subjects.
      The annual progression of AER was significantly higher in the pubertal group than
      in the prepubertal (P = 0.001) or postpubertal (P = 0.001) groups. Six pubertal,
      two postpubertal, and none of the prepubertal subjects developed microalbuminuria
      (AER > or = 20 micrograms/min on two consecutive occasions) over a 3-year period
      (P = 0.047). Multiple logistic regression analysis showed that the risk of
      development of microalbuminuria was increased in pubertal subjects compared with
      the prepubertal and postpubertal subjects (adjusted relative risk [95% CI]: 4.3
      [1.5-9.3], P = 0.012, and 2.1 [1.1-5.0], P = 0.023, respectively). CONCLUSIONS:
      Puberty represents an independent risk of the development of microalbuminuria in
      diabetes. This findings suggests that the endocrine changes of puberty lead to an
      accelerated process of early kidney damage in diabetes. In pediatric diabetes
      care, screening for microalbuminuria is needed soon after the onset of puberty.

PMID- 9614626
TI  - International Diabetes Federation meeting, 1997. Issues in the treatment of type
      2 diabetes; sulfonylureas, metformin, and troglitazone.

PMID- 9614627
TI  - Increased serum levels of advanced glycation end products in NIDDM patients with
      diabetic complications.

PMID- 9614628
TI  - Making things easier is not so easy. The 1997 American Diabetes Association
      criteria and glucose intolerance.

PMID- 9614629
TI  - Hyperhomocysteinemia and microalbuminuria in diabetes.

PMID- 9614630
TI  - Common variable immunodeficiency in adult woman with IDDM.

PMID- 9614631
TI  - Utility of the American Diabetes Association risk test in a community screening
      program.

PMID- 9614632
TI  - Ketoacidosis during gestational diabetes. Case report.

PMID- 9614633
TI  - Discrete trait and dental morphometric affinities of the Tabun 2 mandible.
AB  - Evolutionary scenarios of Near Eastern Middle Paleolithic hominids depend to an
      extent upon whether the terminal Middle Pleistocene Tabun 2 mandible has its
      primary affinities with the late archaic (Neandertal sensu lato) or early modern
      (Qafzeh-Skhul) human lineage in the region. Since the specimen has been assigned
      to each group or seen as bridging them, we have re-examined its morphological
      affinities relative to these two samples, as well as to European samples of later
      Pleistocene hominids. This has been done with respect to posterior corporeal and
      ramal discrete traits, symphyseal morphology, and proportional morphometric
      patterns along the dental arcade. Taking within and between sample ranges of
      variation into account, the lateral corporeal and ramal discrete characters are
      either ambiguous or suggest Neandertal affinities. Anterior symphyseal morphology
      is largely unknown, but a mentum osseum is indicated by a moderate incisura
      mandibulare anterior, and the tuber symphyseos did not extend superiorly toward
      the alveoli, a non-modern arrangement. The lingual symphysis presents the largest
      planum alveolare known for a Near Eastern Middle Paleolithic hominid.
      Morphometric analysis of proportions along the dental arcade separate Tabun 2
      from Near Eastern and European early modern humans and place it among the late
      archaic humans. It is dentally closest to the Near Eastern late archaic human
      lineage and the Krapina sample. These analyses therefore indicate that it is best
      seen as part of the Near Eastern late archaic human lineage with only the mentum
      osseum and incisure shape indicating any approach to the Qafzeh-Skhul humans
      within the Near Eastern Middle Paleolithic.

PMID- 9614634
TI  - Mammalian fauna and biostratigraphy of the pre-Neandertal site of Reilingen,
      Germany.
AB  - In 1978 three well-preserved pieces of a fossil human cranium (i.e., fused
      parietals, occipital and temporal) were found in a gravel pit near the southwest
      German town of Reilingen. It was recovered, with an accompanying mammalian fauna,
      as a side-product of commercial gravel mining. The sample was sorted from the
      dredgings of a boat-mounted crane reaching to a depth of 28 m below the surface.
      Here we present the mammalian fauna and discuss its biostratigraphical relevance.
      The fauna represents a mixture of Holstein interglacial to Wurm glacial species.
      The occurrence of Holsteinian faunal components is indicated by presence of the
      extinct beaver, Trogontherium. Given the good preservation of specimens found at
      the lowest levels we can rule out reworking. The accompanying fauna indicates a
      Holstein to Wurm time span bracketing the fossil hominid population.

PMID- 9614635
TI  - On the phylogenetic position of the pre-Neandertal specimen from Reilingen,
      Germany.
AB  - This paper describes the morphology and phylogenetic significance of a well
      preserved fossil human cranium found near Reilingen, Germany in 1978. The
      specimen consists of two complete parietals, most of the right temporal, and 70%
      of the occipital. The specimen displays several features characteristic of early
      "archaic" Homo sapiens: maximum breadth at the supramastoid crests, roughly
      pentagonal occipital view, an angular torus, superoinferiorly elongate/
      anteroposterior shortened squamous temporal, strong mastoid, and separation of
      the tympanic and mastoid temporal portions. Other features align the Reilingen
      cranium with the "classic" Neandertals: developed suprainiac fossa, bilaterally
      protuberant occipital torus, strong juxtamastoid eminence, a highly convex
      occipital plane, and lambdoid flattening. This morphology and our cephalometric
      analysis support the assignment of this specimen to a Stage 2 "pre-Neandertal"
      group (e.g., Steinheim, Swanscombe, and Atapuerca [SH site]). Following an
      "Accretion Model" of European hominid evolution, Stage 2 succeeds Stage 1
      European "early-pre-Neandertals" (e.g., Mauer and Petralona), and precedes both
      the Saale-Eem Stage 3 "early Neandertals" (e.g., Biache 1), which present greater
      platycephaly, a reduced mastoid process, an enlarged juxtamastoid eminence, and
      true "en-bombe" (parieto-occipital form), and Weichsel Stage 4 "Neandertals"
      (sensu stricto, i.e., "classic" Neandertals).

PMID- 9614636
TI  - The Middle Pleistocene human tibia from Boxgrove.
AB  - The Boxgrove tibia was discovered in 1993, associated with Middle Pleistocene
      fauna, and Lower Palaeolithic archaeology. The sediments at Boxgrove were
      deposited during a temperate interglacial episode and ensuing cold stage. They
      thus represent a wide range of modes and environments of deposition.
      Archaeological remains have been excavated from all the major stratigraphic
      units, giving a continuity of occupation for this part of southern England over a
      10(4) year timescale, through markedly changing climatic regimes. The
      stratigraphic, archaeological and sedimentological contexts of the tibia are
      described, as well as its preservation and morphology. Measurements are given,
      with discussion of reconstructed bone length, and stature estimates. Comparative
      measurements are provided for fossil and recent human samples: the large
      dimensions of its diaphysis place the Boxgrove tibia near or beyond the upper
      size limits of the comparative samples, but its reconstructed length and
      estimated stature are less exceptional. The elevated robusticity of the specimen
      indicates exceptional diaphyseal strength and/or cold adapted body proportions
      paralleling those of the Neanderthals. Disagreement about the taxonomy of Middle
      Pleistocene hominids and lack of comparable fossil material make a specific
      assignment for the Boxgrove tibia problematic. The tibia can only definitely be
      assigned to non-modern Homo sp., with possible further reference to Homo cf.
      heidelbergensis (Schoetensack, 1908) on temporal and geographic grounds, if the
      validity of that species is accepted.

PMID- 9614637
TI  - Non-metric trait evidence for modern human affinities and the distinctiveness of
      Neanderthals.

PMID- 9614638
TI  - Ovarian hyperstimulation syndrome: a new insight into an old enigma.
AB  - OBJECTIVE: To relay the current knowledge on the interaction between cytokines,
      growth factors, and ovarian hyperstimulation syndrome (OHSS) and to propose a new
      insight into the pathogenesis of OHSS. METHODS: Major studies that have reported
      on the association between cytokines, growth factors, and OHSS were identified
      through MEDLINE searches and through the published literature. RESULTS: Several
      cytokines, as well as vascular endothelial growth factor, were found to have a
      role, either in the prediction or pathogenesis of OHSS. Moreover, intravenous
      immunoglobulin, which has an anticytokine nature and inhibits the secretion of
      various cytokines, was shown to prevent the development of OHSS. CONCLUSION:
      Current knowledge indicates a close interaction between cytokines, growth
      factors, and OHSS. Further understanding of these interactions may lead to
      different understanding of ovarian hyperstimulation syndrome.

PMID- 9614639
TI  - A role for hepatocyte growth factor/scatter factor in regulating normal and
      neoplastic cells of reproductive tissues.
AB  - OBJECTIVE: To review data regarding the expression, function, and signal
      transduction pathways associated with hepatocyte growth factor/scatter factor
      (HGF/SF) as related to normal and neoplastic cells of reproductive tissues.
      METHODS: Studies involving HGF/SF were reviewed and the data were summarized.
      RESULTS: Hepatocyte growth factor/scatter factor is generally expressed within
      the stromal components of the testis, prostate, placenta, mammary gland, uterine
      endometrium, and ovary. The receptor for HGF/SF, c-met, is expressed in the
      epithelial cells of these tissues. Ligand activation of c-met results in its
      autotyrosine phosphorylation and the subsequent stimulation of numerous signal
      transduction pathways. Which pathways are activated determine in part the effect
      that HGF/SF has on a specific tissue. Hepatocyte growth factor/scatter factor can
      promote a variety of biologic responses including mitosis, motogenesis (i.e.,
      cell movement), differentiation, and apoptosis. In addition, both HGF/SF and c
      met continue to be expressed during the neoplastic transformation of cells from
      these reproductive tissues. CONCLUSION: Hepatocyte growth factor/scatter factor
      plays an important role in regulating the physiologic function of several
      reproductive tissues and may also be involved in the oncogenesis of cells within
      these tissues.

PMID- 9614640
TI  - Antenatal triiodothyronine improves neonatal pulmonary function in preterm lambs.
AB  - OBJECTIVE: To characterize 1) pulmonary gas exchange, 2) pulmonary function, 3)
      lung fluid and tissue phospholipid content, and 4) thyroid hormone in the
      premature lamb (0.85 of term) after intra-amniotic administration of 100
      micrograms of triiodothyronine (T3) 2 weeks before delivery. METHODS: Nine fetal
      lambs were given 100 micrograms of intra-amniotic T3 under ultrasound guidance at
      112 +/- 1 days' gestation and delivered at 126 +/- 1 days (term = 149 days). Five
      saline-injected animals served as controls. Arterial blood gases, pulmonary
      mechanics, and lung volumes were compared between groups for 1 hour after
      delivery. At delivery, tracheal fluid and blood was taken for T3, and thyroxine
      (T4) levels. Tracheal fluid and lung tissues were assayed for total phosphorus
      and disaturated phosphatidylcholine. RESULTS: Triiodothyronine-treated lambs had
      significantly higher mean arterial pH and lower PCO2 than controls (P < .05) with
      a trend toward higher mean PO2. The dynamic lung compliance was increased by 54%
      with a 40% proportional increase in tidal volume and minute ventilation in the T3
      treated group (P < .05). Functional residual capacity increased 69% (P < .05)
      without a change in specific compliance. The tracheal fluid and pulmonary
      phospholipids and tracheal fluid and plasma T3 and T4 levels were not different
      between the two groups. CONCLUSION: A single 100 micrograms dose of antenatal T3
      significantly improves neonatal gas exchange and lung compliance. The improvement
      in lung function was not accompanied by an increase in pulmonary surfactant
      production. It is inferred that T3 improved lung function via accelerated
      structural development of the lung with an alternative possible effect on
      parenchymal connective tissue matrix.

PMID- 9614642
TI  - Chronic blockade of nitric oxide-synthase and endothelin receptors during
      pregnancy in the rat: effect on pregnancy outcome.
AB  - OBJECTIVES: To investigate the effects of endothelin-1 (ET-1) receptor antagonism
      and/or chronic blockade of nitric oxide (NO) production on pregnancy outcome in
      the rat. METHODS: Pregnant or nonpregnant Wistar rats were either treated orally
      for up to 18 days with the NO-synthase inhibitor N omega-nitro-L-arginine methyl
      ester (L-NAME), the ETA-/ETB-receptor antagonist bosentan (Roche Basel,
      Switzerland) or both, or received no treatment (controls). Blood pressure, body
      weight, and drug intake were measured at regular intervals. Pregnancy outcome and
      proteinurea were also determined. Analysis of variance and paired Student t test
      were used for statistical analysis. RESULTS: Chronic L-NAME treatment increased
      systolic blood pressure by 69 and 64 mmHg in pregnant and virgin rats
      respectively (P < .05). Bosentan-blunted, L-NAME-induced hypertension at the
      beginning (P < .05), but not at the end of the treatment period in all rats
      examined. N omega-nitro-L-arginine methyl ester-treatment in pregnancy reduced
      the number of living fetuses at term (P < .05) and caused proteinurea (P < .05).
      Bosentan tended to reverse the effects of L-NAME on fetus number and proteinurea,
      but both effects failed to reach statistical significance. CONCLUSIONS: The
      effects of chronic, NO-synthase-blockade on blood pressure in gravid rats can be
      reversed only temporarily by ETA-/ETB-antagonism, suggesting an involvement of
      endothelin-1 in the early phase of the L-NAME-induced, preeclampsia-like syndrome
      during pregnancy, although at later stages other mechanisms may come into play.

PMID- 9614641
TI  - Parathyroid hormone-related protein mRNA in sheep endometrium and myometrium
      during late gestation and labor.
AB  - OBJECTIVE: To determine quantitative changes of parathyroid hormone-related
      protein (PTHrP) mRNA in sheep myometrium and endometrium during late gestation
      and labor. METHODS: Tissues were obtained from 22 pregnant ewes under halothane
      anesthesia: early controls at 131 days' gestational age (dGA) not in labor (ECNL;
      n = 6); during cortisol-induced premature labor (CPL at 131 dGA; n = 6); in term
      spontaneous labor (STL at 140-145 dGA; n = 5); or term control animals not in
      labor (TCNL at 140-145 dGA; n = 5). Total RNA was extracted and subjected to
      Northern blot analysis. Blots were probed with a human PTHrP cDNA probe,
      stripped, and rehybridized with an 18s rRNA nucleotide probe to normalize PTHrP
      mRNA levels. RESULTS: Endometrial PTHrP mRNA:18s was unaffected by gestational
      age or labor in tissues from the four groups. In contrast, myometrial PTHrP
      mRNA:18s ratio was decreased when TCNL and STL were compared with both ECNL and
      CPL groups (P < .05). CONCLUSIONS: Significant changes occur at the end of
      gestation in pregnant ovine myometrium PTHrP mRNA but not in the endometrium. In
      myometrium PTHrP mRNA levels were down-regulated at term regardless of whether
      labor was present. It seems that PTHrP mRNA levels in myometrium are related to
      gestational age rather than to labor per se in sheep. We hypothesize that PTHrP
      may play a role in maintaining uterine quiescence until term, at which time
      levels fall allowing myometrial contractile activity to increase unopposed by
      PTHrP.

PMID- 9614643
TI  - Serum nitrites predict the response to prostaglandin-induced delivery at term.
AB  - OBJECTIVE: To evaluate whether the clinical response to prostaglandin-induced
      labor is modulated by nitric oxide (NO) activity. METHODS: Fifty-two cases of
      nulliparous women at term who delivered vaginally after prostaglandin E (PGE)
      induction of labor were enrolled. The induction was required mainly for amniotic
      fluid reduction or late-onset gestational hypertension. Either intracervical (0.5
      mg) or vaginal (2.0 mg) PGE was administered every 12 hours, according to the
      Bishop score. After the third PGE application, in absence of labor onset,
      intravenous oxytocin was used. Nitrites/nitrates (NOx) serum levels were used as
      a marker of NO activity. They were measured just before the start of induction by
      using an enzymatic reduction and then a colorimetric evaluation. Time to delivery
      from the first PGE application was the main outcome variable. RESULTS: Time to
      delivery ranged from 4 to 62 hours (median: 15.5). Nitrites/nitrates levels were
      unaffected by both gestational age, Bishop score at entry, indication allowing
      labor-induction, fetal position, and birth weight. In a multiple regression
      analysis including the previous factors, NOx levels significantly explained 33.9%
      of the variance of the time to delivery. Indeed, patients delivering within 15
      hours (26.4 +/- 6.9) showed NOx levels significantly lower than in patients
      delivering after more than 15 hours (39.5 +/- 16.4) from the first PGE
      application. CONCLUSIONS: A reduced level of NOx is associated with a prompt
      clinical response to PGE-induced labor. Provided we do not know the origin of NOx
      in the general circulation, these data indicate NOx levels as predictors of the
      response to PGE-induced delivery at term and support the hypothesis that labor
      onset is modulated by the endogenous NO activity.

PMID- 9614644
TI  - Effect of estradiol on DHEAS production in the human adrenocortical cell line,
      H295R.
AB  - OBJECTIVE: To determine if estradiol regulates DHEA and DHEAS production in a
      human adrenocortical (H295R) cell line and to determine if this effect is
      receptor mediated. METHODS: NCI-H295 (H295R) cells were rinsed and placed in
      phenol red free Dulbecco's Modified Eagle's-F12 medium supplemented with 0.1%
      charcoal-stripped serum. After 24 hours, cells were rinsed and treated based on
      experimental design. The effects of estradiol were investigated by: 1) treatment
      of cells with increasing concentrations of estradiol (300-3000 nmol/L) with or
      without forskolin (10 mumol/L), 2) treatment of cells with the nonsteroidal
      synthetic estrogen diethylstilbestrol (DES) (300-3000 nmol/L) with or without
      forskolin (10 mumol/L), and 3) treatment of cells with an estradiol antagonist
      (ICI 182, 780) in the presence of estradiol. RESULTS: Estradiol alone increased
      the basal production of DHEAS in H295R cells in a concentration-dependent manner
      with a maximal effect at 1000 nmol/L. Forskolin treatment increased the basal
      production of DHEAS ten-fold. Estradiol also increased the forskolin stimulation
      of DHEAS production two-fold. In contrast, DES alone or DES in addition to
      forskolin did not stimulate DHEAS production. Estradiol, in contrast, inhibited
      H295R adrenal cell production of cortisol whereas DES exhibited a similar
      inhibition. The estrogen receptor antagonist ICI 182,780 was unable to inhibit
      the stimulatory effect of estradiol. Finally, estradiol in a concentration
      dependent manner suppressed 3 beta-hydroxysteroid dehydrogenase (3 beta HSD)
      activity in H295R adrenal cells. CONCLUSION: These experiments support the role
      of estradiol in regulation DHEAS production by inhibiting 3 beta HSD activity;
      however, the mechanism appears to require high concentrations of estradiol and
      appears to be independent of the estrogen receptor.

PMID- 9614645
TI  - Progestin, estrogen, and insulin-like growth factor-I stimulate the prolactin
      receptor mRNA in human endometrial stromal cells.
AB  - OBJECTIVE: To identify the expression of the prolactin receptor (PRL-R) mRNA in
      human endometrial stromal and glandular epithelial cells in order to ascertain
      the autocrine/paracrine actions of PRL and to determine the effect of steroid
      hormones and growth factor on PRL-R mRNA during decidualization. METHODS: Human
      endometrial stromal cells and glandular epithelial cells were isolated from
      tissue fragments by collagenase digestion and total RNA was isolated. Stromal
      cells were cultured with or without progesterone (P) or medroxyprogesterone
      acetate (MPA) for various periods of time. Prolactin receptor and its mRNA were
      determined by Western blot analysis and solution hybridization/ribonuclease
      protection assay. The effects of estrogen, insulin-like growth factor (IGF)-I,
      and PRL on PRL-R mRNA were also studied. RESULTS: Both types of endometrial cells
      expressed PRL-R mRNA. Prolactin receptor mRNA content in glandular cells was
      consistently much less than that in stromal cells (1 versus 5-12). Progesterone
      or MPA stimulated the PRL-R mRNA expression two- to greater than ten-fold in the
      stromal cells of eight endometrial specimens. Stimulation by progestin was
      concentration dependent and required at least 1-2 days' incubation. A high level
      of PRL-R mRNA was maintained in stromal cells beyond 10 days' incubation with
      progestin. The stimulatory effect of progestin was inhibited by RU 486 and by
      cycloheximide, suggesting that progestin-receptor interaction and de novo protein
      synthesis mediate the up-regulation. In addition, estradiol and IGF-I stimulated
      PRL-R mRNA. Western blot analysis showed that progestin increased the PRL-R
      protein. A 90-kd band previously identified as PRL-R was ubiquitously distributed
      in the soluble and particulate fractions of the stromal cells. CONCLUSION: This
      study demonstrated that PRL-R mRNA is expressed in both types of endometrial
      cells and that PRL-R mRNA and its protein are up-regulated by progestin,
      estrogen, and IGF-I during decidualization of endometrial stromal cells.

PMID- 9614646
TI  - Biologic effects of delta-8-estrone sulfate in postmenopausal women.
AB  - OBJECTIVE: To determine in postmenopausal women the biological effects of delta-8
      estrone sulfate, a novel estrogen component of Premarin (Wyeth-Ayerst,
      Philadelphia, PA). METHODS: An open-label, nonrandomized study of six healthy
      postmenopausal women was conducted. Each subject took 0.125 mg of delta-8-estrone
      sulfate daily for 8 weeks. Blood samples were collected at day 0 (baseline) and
      once a week for 8 weeks. Urine was collected on day 0 and at weeks 2, 3, 5, 6, 7,
      and 8. Serum gonadotropins (follicle-stimulating hormone/luteinizing hormone),
      plasma binding proteins (corticosteroid-binding globulin/sex hormone-binding
      globulin), a marker for bone turnover (urinary n-telopeptide), and markers for
      cardiovascular effects (cholesterol, low-density lipoprotein, high-density
      lipoprotein(c), low-density lipoprotein oxidation, and rate of diene formation)
      were measured. RESULTS: Follicle-stimulating hormone levels decreased from 84.0
      +/- 8.5 to 67.0 +/- 8.5 mlU/mL (P = .02), whereas luteinizing hormone levels did
      not change. Corticosteroid-binding globulin levels increased from 3.30 +/- 0.16
      to 4.10 +/- 0.16 mg/dL (P = .02), and no change in sex hormone-binding globulin
      was noted. The n-telopeptide levels decreased an average of 31% from 40.7 +/- 4.9
      to 28 +/- 7.0 nmol/L bone collagen equivalents/mmol/L creatinine (P = .03).
      Plasma diene concentration and diene production rate decreased by 34% and 40%,
      respectively; these changes were not significantly different from baseline
      values. In contrast, a significant (P = .03) 68% increase in the lag time for low
      density lipoprotein(c) oxidation (38.5 +/- 5.5 minutes versus 64.8 +/- 8.5
      minutes) was observed. No significant change occurred in total cholesterol, high
      density lipoprotein(c), and low-density lipoprotein(c). CONCLUSION: Small doses
      (0.125 mg) of delta-8-estrone sulfate have profound estrogenic effects in
      postmenopausal women. The changes observed in n-telopeptide levels and the lag
      time delay in oxidation of low-density lipoprotein(c) indicate that this estrogen
      contributes toward the overall beneficial effects on bone and cardiovascular
      system associated with Premarin therapy.

PMID- 9614647
TI  - Expression of the ErbB family of receptors in ovarian cancer.
AB  - OBJECTIVE: To characterize the relative levels of the ErbB family of receptors
      and their relationship to one another in ovarian cancer. METHODS: A total of 17
      serous cystadenocarcinomas were analyzed for epidermal growth factor receptor
      (EGF-R or ErbB-1) and ErbB-2, ErbB-3, and ErbB-4 receptor expression by Western
      blot analysis. Receptor levels were quantified by densitometry and expressed as
      relative densitometry units normalized to the level of alpha-tubulin. Linear
      regression analysis was used to analyze receptor group differences. A value of P
      < or = .05 was considered statistically significant. RESULTS: All 17 tumors
      expressed detectable levels of EGF-R, ErbB-2, and ErbB-3, but ErbB-4 expression
      was not detected. EGF-R levels correlated with ErbB-2 (r = .70, P < .01) and ErbB
      3 (r = .52, P < .05) levels. The highest correlation was obtained between the
      levels of ErbB-2 and ErbB-3 (r = 0.81, P < .001). CONCLUSION: This study
      indicates an association between the levels of ErbB receptor family members in
      ovarian cancer. This association suggests that one or more coordinated regulatory
      mechanisms may be involved in determining their relative expression levels to one
      another.

PMID- 9614648
TI  - Investigating the mechanism and machinery of RNA editing.
AB  - RNA editing in trypanosomes produces mature mRNAs by posttranscriptional guide
      RNA (gRNA)-directed uridylate insertion and deletion. This article describes
      methods for the study of RNA editing with an emphasis on an in vitro editing
      system that was used to explore the general mechanism of editing and that can be
      adapted for more in-depth studies of this intriguing and important process.
      Methods used to investigate the macromolecular complex that catalyzes RNA editing
      are also described. This complex is composed of multiple proteins and contains
      several catalytic activities. It is in the early stages of characterization. The
      methods described here are intended to assist in its further analysis.

PMID- 9614649
TI  - Biochemical methods for analysis of kinetoplastid RNA editing.
AB  - RNA editing is a posttranscriptional process involving mRNAs [reviewed by K.
      Stuart et al. (1997) Microbiol. Mol. Biol. Rev. 61, 105-120; G. J. Arts and R.
      Benne (1996) Biochim. Biophys. Acta 1307, 39-54; and S. L. Hajduk and R. S.
      Sabatini (1996) in Molecular Biology of Parasitic Protozoa (Smith, D. S., and
      Parsons, M., Eds.), pp. 134-158, Oxford Univ. Press, Oxford] and tRNAs [K. M.
      Lonergan and M. Gray (1993) Science 259, 812-816] that has now been described in
      an increasing number of eukaryotic organisms. In this process sequences differ
      from their gene sequences by the addition, removal, or conversion of specific
      ribonucleotides. RNA editing was first described within the mitochondrion of
      kinetoplastid protozoa. Several of the mitochondrial mRNAs in these flagellates
      have uridine residues inserted and deleted at specific sites. In some cases, more
      than 50% of the mRNA is created by RNA editing. In this article, we describe some
      of the biochemical methods used in analyzing the process of RNA editing in
      kinetoplastid mitochondria.

PMID- 9614650
TI  - Analysis of protein complexes assembled on apolipoprotein B mRNA for mooring
      sequence-dependent RNA editing.
AB  - Apolipoprotein B (apoB) mRNA editing involves a cytidine-to-uridine transition at
      a select site catalyzed by a cytidine deaminase known as APOBEC-1. This enzyme
      cannot edit RNA alone but acquires site-specific editing capacity in the context
      of additional protein factors (auxiliary proteins). These proteins are currently
      hypothesized to assemble with APBEC-1 as a holoenzyme complex or editosome.
      Auxiliary proteins are the focus of ongoing research as they presumably serve
      important structural and regulatory roles in the editosome. The abilities of
      auxiliary proteins to interact with APOBEC-1 and apoB RNA and to promote RNA
      editing activity are important endpoints used as proof that proteins are
      functionally involved in apoB RNA editing. This article reviews the discovery of
      the editosome and provides detailed protocols for its isolation and
      subfractionation.

PMID- 9614651
TI  - Evolutionary analysis of RNA editing enzymes.
AB  - This article focuses on the evolution of apolipoprotein B (apoB) mRNA editing. We
      review the tools commonly used in homology search and phylogenetic analysis and
      demonstrate their use in the analysis of RNA-editing enzymes. The ultimate goal
      is to apply these tools to answer two questions: How did apoB mRNA editing come
      about? How might it be related to other base substitution editing in the course
      of evolution.

PMID- 9614652
TI  - Purification of native and recombinant double-stranded RNA-specific adenosine
      deaminases.
AB  - ADAR1 and ADAR2 are members of a family of enzymes that catalyze the conversion
      of adenosine to inosine in double-stranded RNA. Unlike the other types of RNA
      editing that involve multiprotein editing complexes, the site-specific
      deamination of an adenosine to inosine is catalyzed by single enzymes. ADAR1 and
      ADAR2 have been purified and the genes cloned from various sources. Each gene
      encodes multiple splice variants. As it is crucial to have an adequate supply of
      pure protein to investigate this type of RNA editing, we describe in this article
      methods for both the purification and the overexpression of either full-length or
      partial ADAR1 and ADAR2 isoforms.

PMID- 9614653
TI  - Assays for investigating RNA editing in plant mitochondria.
AB  - In plant organelles transcripts are modified posttranscriptionally by RNA
      editing. This modification process changes almost every protein-coding RNA at
      specific cytidine and uridine positions. Therefore, mitochondrially encoded
      protein sequences differ from the genomically fixed information and show, after
      editing, a higher conservation. To investigate this unusual processing step in
      plant mitochondria, several assays have been developed. However, compared with
      the progress made in other RNA editing fields, knowledge about the factors
      involved in plant mitochondrial editing is limited. One reason for this is the
      lack of a reliable in vitro system for mitochondria. To reveal the biochemical
      nature of the RNA editing reaction in plant mitochondria, we developed an in
      vitro system by which we were able to show that cytidine is specifically modified
      to uridine by a deamination or transamination process. Here we describe the
      development of a pea in vitro system and discuss assays to follow the editing
      process.

PMID- 9614654
TI  - Analysis of RNA editing in plastids.
AB  - Chloroplast mRNAs can be subject to posttranscriptional pyrimidine-to-pyrimidine
      conversions at highly specific sites. This RNA modification mechanism shows a
      high degree of similarity to plant mitochondrial editing but differs markedly
      from, and is most likely evolutionarily unrelated to, all other RNA editing
      systems. The study of RNA editing processes in chloroplasts has been largely
      hampered by the lack of in vitro editing systems; however, considerable insights
      into the recognition mechanisms of individual editing sites have come from in
      vivo approaches. Chloroplast transformation proved to be a particularly useful
      tool to study plastid RNA editing. In this article, specific methods for the
      analysis of chloroplast RNA editing are discussed. Detailed experimental
      procedures are provided for (i) the purification of chloroplasts and (ii) the
      stable genetic transformation of higher plant plastids.

PMID- 9614655
TI  - Left ventricular diastolic dysfunction: pathophysiology, diagnosis and treatment.

PMID- 9614656
TI  - Non-operative management of patients with coronary artery disease: current
      indications for percutaneous coronary angioplasty.

PMID- 9614657
TI  - A critical analysis of the concept of silent myocardial ischaemia.

PMID- 9614658
TI  - Arterial function in renal failure.

PMID- 9614659
TI  - Coronary vascular endothelium, a common target in patients with diabetes
      mellitus, cigarette smoking, hypercholesterolaemia, hypertension and menopausal
      status.

PMID- 9614660
TI  - Acquired abdominal aortic aneurysm.

PMID- 9614661
TI  - Exploration and treatment of carotid stenoses in 1996.

PMID- 9614662
TI  - Lipid disorders and cardiovascular risks in nephrology.

PMID- 9614663
TI  - Can the genes of hypertension be identified?

PMID- 9614664
TI  - Uraemic cardiomyopathy.

PMID- 9614665
TI  - Aortic stenosis in chronic renal failure patients treated by dialysis.

PMID- 9614666
TI  - Accelerated arterial disease in renal transplant recipients.

PMID- 9614667
TI  - Slow continuous and daily ultrafiltration for refractory congestive heart
      failure.

PMID- 9614668
TI  - Peritoneal ultrafiltration and treatment-resistant heart failure.

PMID- 9614669
TI  - Swallows, oesophageal and gastric motility in normal subjects and in patients
      with gastro-oesophageal reflux disease: a 24-h pH-manometric study.
AB  - BACKGROUND: the motor aspects underlying gastro-oesophageal reflux disease (GORD)
      are still not completely clear. AIM: to evaluate the relationship between
      oesophageal and gastric motility in GORD patients. PATIENTS: twelve patients with
      grade I-II oesophagitis, mean age 45 yr, and 10 healthy subjects, mean age 42 yr,
      were studied. METHODS: a pH-manometry was performed to analyse oesophageal and
      gastric motility, swallows and oesophageal pH values for the whole 24-h period,
      and for the 2-min period before and after each reflux episode. RESULTS: as
      compared to controls, GORD patients showed in the 24-h period, a greater number
      of swallows (P < 0.01) and a lower percentage of post deglutitive propagated
      oesophageal body waves (P < 0.05). The number of migrating motor complexes (MMC)
      was similar in the two groups, with a lower amplitude of phase III gastric waves
      in GORD. During MMC reflux episodes were seen only in GORD patients. After
      refluxes an increase in swallows, simultaneous and secondary oesophageal waves
      were detected in GORD patients, with a reduction of primary peristalsis. Isolated
      gastric contractions preceded reflux episodes more frequently in GORD patients
      than in controls. CONCLUSIONS: GORD patients showed an increase in swallows with
      altered post-deglutitive oesophageal motility and a reduced amplitude of gastric
      MMC. Moreover small contractions of gastric antrum are present before acid
      refluxes, suggesting a multifactorial pathogenesis of the disease.

PMID- 9614670
TI  - Post- and presynaptic effects of norepinephrine in guinea-pig colonic submucous
      plexus.
AB  - Intracellular recording techniques were used to investigate the effects of
      norepinephrine on submucous neurones in the guinea-pig distal colon. In 81% of
      the neurones, pressure microejection of norepinephrine produced a membrane
      hyperpolarization associated with a decrease in excitability and input
      resistance. Microejection of clonidine (1 microM) mimicked the norepinephrine
      induced hyperpolarization, whereas both phentolamine (1 microM) and yohimbine (1
      microM) reversibly suppressed it. Superfusion of norepinephrine (1 nM - 10
      microM) hyperpolarized the cells in a concentration-dependent manner.
      Norepinephrine and clonidine (1 nM - 10 microM) caused a concentration-dependent
      presynaptic inhibition of stimulus-evoked cholinergic fast excitatory
      postsynaptic potential. Slow inhibitory post-synaptic potentials (sISPSs) were
      induced by focal electrical stimulation of the interganglionic fibre tracts in
      43% of the neurones tested. Superfusion of both phentolamine (1 microM) and
      yohimbine (1 microM) reduced the sIPSPs while prazosin (1 microM) had no
      significant effect. We concluded that norepinephrine acted post- and
      presynaptically via alpha 2-adrenoreceptors to have an inhibitory effect on the
      guinea-pig colonic submucous. In addition, our study strongly supported the role
      of norepinephrine as a mediator of the sIPSPs. As a result, norepinephrine would
      primarily suppress information transfer within the neuronal circuits in guinea
      pig colonic submucosal plexus.

PMID- 9614671
TI  - Changes in pyloric resistance induced by erythromycin.
AB  - Erythromycin increases gastric emptying but the characteristics of transpyloric
      flow and the contribution of pyloric resistance to the mechanisms of increased
      flow are unknown. Transpyloric outflow and gastroduodenal pressures were studied
      in eight anaesthetized pigs during intravenous infusion of erythromycin (10 mg kg
      1). Erythromycin increased emptying of saline through an increased stroke volume
      of individual flow pulses (13.7 +/- 1.24 vs. 3.6 +/- 1.30 mL) rather than by
      decreasing the interval between flow pulses (3.9 +/- 0.55 vs. 3.2 +/- 0.30
      pulse.min-1). This flow pattern was associated with more frequent antral
      contractions of larger amplitude originating from the upper part of the gastric
      antrum, suppression of isolated pyloric pressure waves and significant reduction
      of the pyloric resistance to flow (2.3 +/- 0.21 vs. 4.6 +/- 0.46 mmHg mL-1 s-1).
      The decreased resistance originated from a different temporal relationship
      between antropyloric pressure event and flow pulses that occurred almost
      simultaneously during erythromycin.

PMID- 9614672
TI  - A novel portable perfused manometric system for recording of small intestinal
      motility.
AB  - The development of solid-state catheters with miniature pressure transducers and
      portable dataloggers with a large memory capacity has allowed recording of
      gastrointestinal motility in ambulant subjects. Developments in silicone rubber
      extrusion technology made it possible to build a perfused manometric system,
      using a perfused manometric assembly requiring a low volume of perfusate. In the
      present study the feasibility of recording and automated analysis of small
      intestinal motility using a perfused multiple lumen manometric system was
      evaluated in seven healthy volunteers. Pressures were recorded from 12 sideholes
      arranged in four clusters spaced at 10-cm intervals from the catheter tip. Each
      channel was perfused at 0.15 mL min-1 with degassed water by a portable, low
      compliance, perfusion pump. The 12 sidehole recording channels were connected to
      external transducers mounted on a belt. Pressure data were stored in two
      dataloggers. Motility was recorded in the sitting (30 min), and supine (30 min)
      position, during walking (30 min) and postprandially (90 min). Using purpose
      built software baseline variations were corrected for and manometric variables
      (number of pressure waves, mean amplitude and motility index) calculated. Bench
      testing of the manometric assembly showed a median baseline pressure offset of
      4.2 kPa (range 3.7-10.1) and upon occlusion a rise rate of 27.8 kPa sec-1 (range
      19.7-30.8). Changes in body position affected baseline pressures so that compared
      to the supine position changes in baseline pressure varied between 1.5 +/- 0.7
      kPa and 1.9 +/- 0.6 kPa during sitting (P < 0.02), and between 1.7 +/- 0.7 kPa
      and 1.5 +/- 0.9 kPa during walking (P < 0.03). Manometric recordings obtained
      during the fasting period showed an increase in small intestinal motor activity
      during walking. In the postprandial period no differences in motility variables
      were observed within one cluster and in time. Recording of small intestinal
      motility with a multiple-channel silicone rubber manometric assembly with a
      portable perfusion system is a feasible technique which is relatively
      inexpensive. Computer-assisted data processing allows for adequate elimination of
      artefacts and automated numerical analysis.

PMID- 9614673
TI  - Activation of non-adrenergic non-cholinergic inhibitory pathways by endogenous
      and exogenous tachykinins in the ferret lower oesophageal sphincter.
AB  - Repeated oesophageal acidification causes lower oesophageal sphincter (LOS)
      relaxation in the anaesthetized ferret which is mediated by a peripheral
      neurokinin (NK-1) receptor mechanism. Our aim in this study was to characterize
      neural pathways in the LOS activated by capsaicin and tachykinin receptor
      agonists in vitro. Circular muscle strips of LOS (two per animal) from a total of
      24 ferrets were maintained in organ baths. Electrical field stimulation (EFS, 50
      V, 5-50 Hz) caused frequency-dependent LOS relaxation which was abolished by
      tetrodotoxin (TTX; 10(-6) M: P < 0.001) and reduced by N(G)-nitro-L-arginine (L
      NNA; 10(-4) M: P < 0.01). Substance P and [Sar9, Met (O2)11]-substance P
      (selective NK-1 agonist) caused dose-dependent relaxation, while the NK-2
      receptor agonist [beta-Ala8]-NKA 4-10 evoked excitation. Capsaicin (10(-6) M)
      caused relaxation and desensitization that was overcome by long recovery periods
      and substance P dosing (10(-8) M). After pretreatment with the NK-1 receptor
      antagonist CP 99994 (10(-7) M), substance P (10(-8) M; P < 0.001) and capsaicin
      (10(-6) M: P < 0.01)-induced relaxations were reduced. In the presence of TTX
      (10(-6) M), excitation resulted in response to substance P (10(-8) M; P < 0.05)
      and [Sar9, Met (O2)11]-substance P (10(-8) M; P < 0.001), while the response to
      [beta-Ala8]-NKA 4-10 (10(-7) M) was unaffected. In the presence of L-NNA (10(-4)
      M), substance P and [Sar9, Met (O2)11]-substance P-induced relaxations were
      reduced (10(-8) M; P < 0.01), while the response to [beta-Ala8]-NKA 4-10 (10(-7)
      M) was unaffected. These results show that functional coupling between capsaicin
      sensitive sensory neurones and NANC inhibitory neural pathways occurs via NK-1
      receptors in the ferret LOS. NK-2 (and some NK-1) receptors activate non-neural
      excitatory mechanisms. Substance P and NK-1 receptors coupling sensory and NANC
      inhibitory neurones may be important in the reflex control of LOS motility.

PMID- 9614674
TI  - A model for evaluation of gastric sensitivity in awake rats.
AB  - We developed a model for the evaluation of gastric sensitivity to distension in
      awake rats. A balloon made from a latex condom was chronically placed in the
      stomach and three stainless steel electrodes were implanted in the neck muscles.
      Isobaric distensions were performed with a barostat by step of 5 mmHg with 10 min
      inflation and 2 min deflation. Gastric pressure, integrated neck electromyogram
      (EMG) and gastric volume were continuously monitored on a potentiometric
      recorder. Gastric distension at 15 or 20 mmHg induced a typical posture
      associated with contractions of the neck muscles. Pain threshold was defined as
      the pressure inducing an increase of integrated neck EMG greater than 100%. The
      mean pain threshold was 18.5 +/- 0.7 mmHg and was not modified 2, 4 and 7 days
      after the first experiment. However, gastric volumes were significantly higher on
      the 4th and the 7th days. Morphine at the doses of 0.4 and 4 mg kg-1 i.p.
      significantly increases the pain threshold. At the doses of 0.04 and 0.4 mg kg-1,
      morphine significantly increased gastric volume for the distending pressure of 10
      mmHg. Naloxone (2.5 mg kg-1 i.p.) reversed the effects of morphine. In
      conclusion, our model permits simultaneous evaluation of pain threshold and
      gastric compliance associated with gastric distension in conscious rats.

PMID- 9614675
TI  - Substance P stimulates sphincter of Oddi motility and inhibits trans-sphincteric
      flow in the Australian brush-tailed possum.
AB  - Substance P containing nerves are widely distributed throughout the
      gastrointestinal tract. The aims of this study were to determine the distribution
      of substance P containing nerves in the extrahepatic biliary tree of the
      Australian brush-tailed possum and to characterize the effect of exogenous
      substance P on the sphincter of Oddi (SO) motility and transphincteric flow in
      vivo. Immunohistochemical staining of fixed specimens (n = 8) found moderate
      numbers of substance P containing nerve cell bodies and fibres throughout the
      neural plexuses of the SO, in particular in the serosal and intraluminal nerve
      trunks of the SO and gallbladder. Synthetic porcine substance P (1-2000 ng kg-1),
      administered by close intra-arterial injection (i.a.; n = 7), produced a dose
      dependent elevation in basal pressure [P < 0.01] and an associated dose-dependent
      reduction in trans-sphincteric flow [P < 0.0001]. Substance P had no significant
      dose-dependent effect on SO phasic contraction amplitude or frequency.
      Tetrodotoxin (9 micrograms kg-1, i.a.) did not inhibit the effect of substance P
      on SO motility and trans-sphincteric flow (n = 5). In conclusion, substance P
      containing nerves are found throughout the possum extrahepatic biliary tree.
      Exogenous substance P stimulates SO motility and reduces trans-sphincteric flow
      in vivo by acting directly on the sphincter smooth muscle.

PMID- 9614676
TI  - Effect of meal temperature on the frequency of gastric myoelectrical activity.
AB  - It was hypothesized that the transient post-prandial decrease of the dominant
      frequency in the electrogastrogram (EGG) is related to the temperature of the
      meal. In a randomized three-period cross-over design. EGG recordings were made in
      10 healthy volunteers. A liquid meal (36 kcal, 300 mL) was ingested at either 4,
      37 or 55 degrees C. The changes in the dominant EGG frequency that occurred in
      the first 25 min postprandial were calculated using running spectrum analysis.
      After the meal a transient shift in frequency was seen, which was significantly
      greater after the cold meal than after the other meals (P < 0.001), with a
      greater decrease in the dominant frequency (4 degrees C: -0.75 [-0.92(-)-0.68],
      37 degrees C: -0.34 [-0.51(-)-0.18], 55 degrees C: -0.30 [-0.45(-)-0.12] cpm; P =
      0.020) and a longer duration (4 degrees C: 16 [13-19], 37 degrees C: 12 [6-14],
      55 degrees C: 5 [3-8] min; P = 0.014). No differences were found between the 37
      degrees C and 55 degrees C meals, the power ratios or the number of dysrhythmias.
      The magnitude of the postprandial shift in frequency of gastric myoelectrical
      activity depends on the temperature of the meal. Meal temperature should be taken
      into account in studies on postprandial gastric motility.

PMID- 9614677
TI  - Third-party reimbursement.

PMID- 9614678
TI  - Dysfunctional uterine bleeding in adolescents.
AB  - Dysfunctional uterine bleeding is a common complaint in adolescent girls.
      Clinicians working in pediatric, internal medicine, and gynecology offices and in
      emergency departments are often called upon to make this diagnosis. Dysfunctional
      bleeding is defined as irregular, painless bleeding of endometrial origin that
      may be excessive, prolonged, or unpatterned. Although the bleeding is usually
      secondary to anovulation, the diagnosis is one of exclusion. To make an accurate
      diagnosis, the clinician must understand the normal adolescent menstrual cycle
      and related hormone feedback mechanisms. This article reviews the normal hormone
      mechanisms in the adult and adolescent menstrual cycles in an effort to guide the
      clinician through the diagnosis. Potential causes and recommended treatment
      modalities are reviewed.

PMID- 9614679
TI  - Managing atrial fibrillation to prevent its major complication: ischemic stroke.
AB  - Atrial fibrillation is an acute or chronic arrhythmia that occurs postoperatively
      or during intense emotional stress, exercise, or acute alcohol intoxication. More
      than 10% of Americans aged 75 and older have atrial fibrillation, which is common
      in elderly patients with cardiopulmonary disorders. During atrial fibrillation,
      uncoordinated electrical activity leads to ineffective atrial contraction,
      reduced atrial filling time, and decreasing cardiac output. Blood flow stasis may
      cause thrombi to form in the quivering atria. Cardioversion may be indicated to
      convert an unstable patient into sinus rhythm. However, if cardioversion converts
      the patient's status to sinus rhythm, thrombi may become dislodged and propelled
      into the bloodstream as emboli. Occlusion of a cerebral blood vessel often
      follows, leading to stroke. Because patients with longstanding atrial
      fibrillation are predisposed to stroke, anticoagulation therapy (usually with
      heparin, warfarin, or aspirin) should be initiated 3 weeks prior to
      cardioversion. Proper anticoagulation can usually prevent ischemic stroke.

PMID- 9614680
TI  - Advance directives and advocacy in end-of-life decisions.
AB  - This article examines the issue of advocacy for all adults in end-of-life
      decisions to help enhance the role of health care providers as partners in
      decision making. The ethical issues of death and dying are of particular concern
      for the elderly. Conflicts may prevent providers and nurses from creating a good
      dying experience for patients and family. Among the many issues associated with
      end-of-life decision making are futility, autonomy, and quality of life, a "good
      death," advance directives, family distress, and the culture of medicine. To
      overcome related barriers, involved health care providers can promote advocacy by
      offering choices in end-of-life care and providing an environment of listening
      and communication. Initiating and maintaining dialogue on this difficult subject
      will provide better care to patients and families.

PMID- 9614681
TI  - Diagnosis and treatment of leptospirosis in the primary care setting.
AB  - Leptospirosis is an infectious illness that usually develops 1 to 2 weeks after
      indirect or direct exposure to the urine of infected animals. Infection occurs
      through open cuts, absorption through intact mucous membranes, and drinking
      contaminated water. The typical presentation is a flulike syndrome of sudden
      onset that tends to resolve within 2 weeks. A mild immunologic phase usually
      presents as an aseptic meningitis. A more severe immunologic phase (Well's
      syndrome) can result in jaundice, renal failure, adult respiratory distress
      syndrome, disseminated intravascular coagulation, and death. Laboratory tests
      take too long to replace clinical diagnosis, which is imperative so that
      antibiotic therapy can begin before the fourth day of illness. Although
      leptospirosis is more common in tropical climates, detection in the continental
      United States is increasing. Early, accurate detection and treatment in the
      primary care setting are vital for limiting life-threatening complications.

PMID- 9614682
TI  - Altered bleeding time associated with ibuprofen and zidovudine use.
AB  - The purpose of this article is to describe a patient who was HIV-positive, had a
      massive venous ulcer, and developed a prolonged bleeding time with marked blood
      loss from the ulcer. The patient underwent a workup to rule out possible causes
      for this prolonged bleeding time; all studies were negative. A review of his
      history identified that he was self-medicating with ibuprofen while taking
      zidovudine. A potentiated effect of these two medications on the bleeding time
      has been reported in the literature. This case illustrates the importance of
      revisiting a patient's history while working up an acute problem as well as
      clinically monitoring for blood loss if a person takes ibuprofen and zidovudine.

PMID- 9614683
TI  - Mibefradil: a new twist to the calcium channel antagonist.

PMID- 9614684
TI  - New treatments for stroke.
AB  - Stroke is the third leading cause of death and the leading cause of adult
      disability in the United States. With an annual incidence of over 500,000, stroke
      has enormous social and economic consequences. Ischemic stroke comprises over 80%
      of all strokes, with strokes caused by intracerbral hemorrhage and subarachnoid
      hemorrhage making up the rest. Recent advances in the understanding of stroke
      risk factors and the mechanisms of nervous system damage in acute stroke,
      especially ischemic stroke, have led to new therapies for both prevention and
      treatment. Anticoagulation with warfarin can prevent cardioembolic stroke
      resulting from atrial fibrillation. Carotid endarterectomy can prevent stroke
      caused by internal carotid artery stenosis. Tissue plasminogen activator, a clot
      dissolving medication, has recently been proven effective in acute ischemic
      stroke if administered within three hours of onset. Despite these advances,
      stroke remains common, and most acute stroke unfortunately remains untreatable.
      Current and future approaches emphasize educating the public and healthcare
      professionals regarding stroke warning signs and the need for emergent care.
      Active clinical research is exploring even newer treatments based on the
      scientific basis of stroke neurobiology.

PMID- 9614685
TI  - Arrhythmia detection and response in a monitoring technician and pocket paging
      system.
AB  - Technologically advanced telemetry systems have begun to produce alternatives to
      the need for continuous visual observation of the electrocardiogram (ECG). Few
      studies have been conducted to determine the efficacy of these systems in the
      clinical setting. The purpose of this study was to describe two different
      approaches to communication of arrhythmia events and corresponding nurse
      response. One approach, on a cardiac medical unit, utilized a monitoring
      technician to continuously observe ECGs at a central monitoring technician
      station (MTS) and notify the nurse of changes. The other approach, on a general
      medical unit, eliminated the use of the monitoring technician and utilized a
      pocket paging system (PPS). The PPS interfaced with the computerized arrhythmia
      detection system from the ECG monitor, which directly alerted the nurse to
      arrhythmia events. A quasi-experimental comparative post-test design was used.
      The sample consisted of 50 randomly selected, 2-hour observation periods on each
      unit during a 3-month period. Data collectors recorded the interaction of the
      monitoring technician with the arrhythmia detection system and the nurse on the
      MTS unit, or the nurse using the PPS. Results of this study revealed all
      arrhythmia events activated an alarm by the computerized arrhythmia detection
      system. Length of time to notify the nurse was within 0 to 1 minute for both
      systems. This study demonstrated that the PPS is a viable approach to arrhythmia
      detection and communication in the medical/cardiac patient population.

PMID- 9614686
TI  - Stages of exercise behavior change at two time periods following coronary artery
      bypass graft surgery.
AB  - A sedentary lifestyle is the most prevalent coronary heart disease risk factor in
      the United States. It is a challenge for healthcare providers to promote the
      adoption and maintenance of regular exercise as a lifestyle change in sedentary
      individuals. For this effort to be effective, research on exercise behavior and
      the processes that promote the desired behavior is needed. Using the
      Transtheoretical Model of Change (TMC), this study was aimed at describing and
      comparing short- and long-term regular exercise behavior and the change processes
      used in the different stages, with subjects after coronary artery bypass graft
      (CABG) surgery. Questionnaires were sent to 253 patients aged 60 years and older
      at 4 to 6 months and 22 to 26 months after CABG surgery. The study findings
      indicate that 67% of the subjects had become long-term regular exercisers.
      However, there were more subjects who had begun exercise shortly after the
      surgery than at the 2-year point. The data suggest that health promotion efforts
      may be more cost-effective and efficient if focused on educating the smaller
      percentage of post-CABG surgery patients in the pre-regular-exercise stages. In
      addition, relapse prevention may be needed to maintain exercise adherence. This
      study also demonstrates that exercise behavior can be easily categorized into
      stages with the use of four questions. However, an instrument to evaluate the
      processes of exercise behavior change needs to be developed specifically for the
      older population.

PMID- 9614687
TI  - Low-molecular-weight heparins in the management of cardiovascular conditions.

PMID- 9614688
TI  - The many rhythms of digitalis toxicity.

PMID- 9614689
TI  - Kinetics of racemization of (+)- and (-)-diethylpropion: studies in aqueous
      solution, with and without the addition of cyclodextrins, in organic solvents and
      in human plasma.
AB  - The configurational stability of (+)- and (-)-diethylpropion [(+)- and (-)-2
      (diethyl)-1-phenyl-1-propanone or (+)- and (-)-DEP] was investigated
      systematically from chemical, pharmaceutical, and pharmacological aspects. The
      enantiomeric ratio was monitored directly with a recently developed stability
      indicating enantioselective HPLC method. In aqueous solutions, the rate of
      racemization increased non-linearly with increasing pH and with increasing
      phosphate buffer concentration. The racemization rate showed a positive slope
      with increasing temperature and decreasing ionic strength. The racemization rates
      of (+)- and (-)-DEP in the presence of cyclodextrins (CDs) did not differ
      significantly. CDs that were added to (+)- and (-)-DEP in a molar ratio 5:1
      showed the following effects after dissolution in 10 mM phosphate buffer (final
      pH 6.7): sulfobutyl ether-beta-CD (SBE-beta-CD) and methylated-beta-CD (Me-beta
      CD) retarded racemization; whereas hydroxypropyl-beta-CD (HP-beta-CD), acetyl
      gamma-CD (Ac-gamma-CD), acetyl-beta-CD (Ac-beta-CD), gamma-CD, and beta-CD showed
      a weak destabilising effect. In contrast to the described CDs, alpha-CD
      distinctly accelerated the rate of racemization. The configurational stability of
      (+)- and (-)-DEP was also studied under physiological conditions. The half-life
      of racemization in heparinised human plasma was for both enantiomers determined
      to be approximately 23-25 min. In phosphate buffer (10 mM, pH 7.4), rac-DEP
      showed a high, but unselective affinity towards human alpha 1-acid glycoprotein
      (orosomucoid) immobilised on silica (Chiral AGP). The rate of racemization of the
      free base of (-)-DEP dissolved in organic solutions generally increases with the
      polarity of the solvating agent.

PMID- 9614690
TI  - Stereoselective renal secretion of carbenicillin in rabbits: role of the organic
      anion transporter at the renal brush border membrane.
AB  - Stereoselectivity in the renal secretion of carbenicillin (CBPC) was studied in
      rabbits. Significant renal secretion of CBPC was observed in vivo, with the
      secretion of the S-epimer being greater than that of the R-epimer.
      Stereoselective transport of CBPC was further studied in vitro using basolateral
      and brush border membrane vesicles prepared from rabbit kidneys. The transport of
      CBPC by the organic anion transporter into the basolateral membrane vesicles
      (BLMV) was not stereoselective. In contrast, a distinct stereoselectivity was
      observed in the transport of CBPC by the organic anion transporter into the brush
      border membrane vesicles (BBMV), with the transport of the S-epimer being more
      favorable. Significant epimer-epimer interactions were also observed in the
      transport into BBMV. The stereoselectivity of the transport of CBPC was
      calculated from the kinetic parameters with consideration of epimer-epimer
      interactions and was similar to that observed in vivo. It was concluded that the
      observed stereoselectivity in the renal secretion of CBPC in vivo reflected that
      of transport via the organic anion transporter located at the brush border
      membrane.

PMID- 9614691
TI  - Separation, characterization, and specificity of alpha-mannosidases from Vigna
      umbellata.
AB  - Information about the specificity of glycosidase enzymes is important since it
      affects their use for characterization and synthesis of oligosaccharides. Two
      alpha-mannosidases (EC 3.2.1.24), I and II, were isolated from rice beans (Vigna
      umbellata). The native molecular weight of both isozymes was estimated to be
      329,000, but pIs of form I were 5.03-5.34 and pIs of form II were 5.46-6.20. The
      two isozymes were characterized in terms of optimal pH and temperature, effects
      of metal ions, inhibition by swainsonine and 1-deoxymannojirimycin, and kinetic
      parameters for p-nitrophenyl-alpha-D-mannopyranoside and Man alpha (1-2)Man. Both
      enzymes were more specific towards Man alpha (1-2)Man in both hydrolysis and
      synthesis, but their hydrolytic specificities towards Man alpha (1-3)[Man alpha
      (1-6)]Man were different.

PMID- 9614692
TI  - NADH-dependent inhibition of branched-chain fatty acid synthesis in Bacillus
      subtilis.
AB  - Addition of NADH to crude but not to pure branched-chain alpha-keto acid
      decarboxylase decreased the CO2 production from alpha-keto-beta-methylvalerate
      (KMV) suggesting the presence of an NADH dependent inhibitor in the crude enzyme
      from Bacillus subtilis. This NADH-dependent decarboxylase inhibitor was purified
      to homogeneity by a fast protein liquid chromatography system. The purified
      inhibitor was identical with leucine dehydrogenase as to N-terminal amino acid
      squence (35 residues) and molecular weight, and catalyzed the oxidative
      deamination of three branched chain amino acids (BCAAs), valine, leucine, and
      isoleucine. The decarboxylase inhibitor was therefore identified as leucine
      dehydrogenase. A decreased substrate availability caused by leucine dehydrogenase
      thus reasonably accounted for the NADH dependent inhibition of the
      decarboxylation. In turn, the observation that leucine dehydrogenase competes
      with the decarboxylase for branched-chain alpha-keto acid (BCKA) suggested an
      involvement of this enzyme in the branched chain fatty acid (BCFA) biosynthesis.
      This view was supported by the observation that addition of NAD to crude fatty
      acid synthetase increased the incorporation of isoleucine into BCFAs. Pyridoxal
      5'-phosphate and alpha-ketoglutarate, cofactors for BCAA transaminase, modulated
      BCFA biosynthesis from isoleucine in vitro, suggesting also the involvement of
      transaminase reaction in BCFA biosynthesis.

PMID- 9614693
TI  - Effects of O-glycosylation inhibitors on the differentiation of HL-60 cells.
AB  - The effects of O-glycosylation inhibitors on the growth and differentiation of
      the human acute promyeloblastic leukemia cell line HL-60 were studied to examine
      whether the O-glycosylation is needed for HL-60 cells to differentiate into
      granulocyte-like cells or monocyte-macrophage-like cells. N-Acetyl-alpha-D
      galactosaminides, inhibitors of mucin-type oligosaccharide synthesis, and N
      acetyl-beta-D-galactosaminides did not affect either growth or differentiation.
      beta-D-Xylosides, the artificial initiators of glycosaminoglycan synthesis, also
      were tested. Only 4-methylumbelliferyl-beta-D-xyloside induced HL-60 cells, to
      differentiate, and they differentiated into granulocyte-like cells, assessed by
      reduction of nitroblue tetrazolium, Giemsa staining, and esterase double
      staining. The aglycon portion of 4-methylum-belliferyl-beta-D-xyloside, 4
      methylumbelliferone, caused the differentiation. Thus we could find a new drug
      that induces the differentiation of HL-60 cells.

PMID- 9614694
TI  - Phytotoxins from the Septoria spp. plant pathogenic fungus on leafy spurge.

PMID- 9614695
TI  - Isolation and primary structure of a methionine- and cystine-rich seed protein of
      Cannabis sativa.
AB  - A 10-kDa protein was isolated from resting seeds of hemp (Cannabis sativa) by
      buffer extraction, gel filtration, ion-exchange chromatography, and reversed
      phase high-pressure liquid chromatography. The protein did not inhibit bovine
      trypsin. It consisted of subunits composed of 27 and 61 residues and was held
      together by two disulfide bonds. The complete amino acid sequence was identified
      by protein analysis, and had 20 mole% of amino acids containing sulfur. The
      protein was most similar to a methionine-rich protein of Brazil nut (Bertholletia
      excelsa) and to Mabinlin IV, a sweetness-inducing protein of Capparis masaikai.
      The high methionine content and the absence of trypsin inhibitory activity
      suggested that the seed protein can be used to improve the nutritional quality of
      plant food-stuffs.

PMID- 9614696
TI  - Optimization for beta-mannanase production of a psychrophilic bacterium,
      Flavobacterium sp.
AB  - We found that a psychrophilic bacterium, Flavobacterium sp., characterized in
      this study, has a beta-mannanase (EC 3.2.1.78) activity in the culture medium.
      The mannanase activity was the highest in the culture medium, containing 1.0%
      (w/v) guar gum (as a carbon source), 0.3% (NH4)2SO4 (as a nitrogen source), and
      0.06% (w/v) yeast extract, of five-days cultivation at 4 degrees C. No mannanase
      activity was found in the medium containing a monosaccharide or a disaccharide as
      a carbon source, although the psychrophile could use them. The enzyme activity
      was found only when the bacterium was cultured in the medium containing a
      polysaccharide. The enzyme preparation showed a single activity band on a washed
      gel of SDS-PAGE. The optimal temperature for the enzyme activity was 35 degrees
      C. When the reaction was done at 10 degrees C, the enzyme showed 25% of the
      optimal activity. The beta-mannanase preparation efficiently hydrolyzed guar gum,
      locust bean gum, and glucomannan as well as beta-mannan.

PMID- 9614697
TI  - Purification and partial characterization of purine nucleoside phosphorylase from
      Serratia marcescens.
AB  - Purine nucleoside phosphorylase (PNP) was purified to homogeneity. The molecular
      weight of the enzyme was 170,000. The enzyme consisted of six subunits, each with
      a molecular weight of 27,000. Serratia PNP had ten times the affinity for
      adenosine and deoxyadenosine than for inosine and deoxyinosine in a pattern
      characteristic of bacterial PNP. 1-Methylinosine and 1-methylguanosine, which
      have no affinity for mammalian PNP, bound Serratia PNP. In terms of Kcat/K(m),
      the substrate specificities were in the descending order of guanosine, inosine,
      and adenosine. When inosine or deoxyinosine was used as a variable substrate, a
      biphasic reciprocal plot with upward curvature was observed. The values of the
      Hill coefficient were 1.2 and 1.1 for inosine and deoxyinosine, respectively.
      Positive cooperativity seemed to be involved in the binding of inosine and
      deoxyinosine to the enzyme.

PMID- 9614698
TI  - Effects of dietary alpha-linolenic, eicosapentaenoic and docosahexaenoic acids on
      hepatic lipogenesis and beta-oxidation in rats.
AB  - The effects of dietary alpha-linolenic, eicosapentaenoic and docosahexaenoic
      acids on the enzyme activities related to hepatic lipogenesis and beta-oxidation
      were compared under constant polyunsaturated/monounsaturated/saturated fatty
      acids and n-6/n-3 ratios of dietary fats in rats. Dietary fat containing linoleic
      acid as the sole polyunsaturated fatty acid (PUFA) was also given as a control.
      The concentration of serum triglyceride and phospholipid in the three n-3 PUFA
      groups was lower than in the linoleic acid group. The hepatic triglyceride
      concentration was lower and the phospholipid concentration was higher in the
      three n-3 PUFA groups than in the linoleic acid group. Cytosolic fatty acid
      synthase (FAS) activity was lower in the n-3 PUFA groups than in the linoleic
      acid group, the reduction being more predominant in the eicosapentaenoic acid and
      docosahexaenoic acid groups than in the alpha-linolenic acid group. The cytosolic
      activities of the NADPH-generating enzymes, glucose-6-phosphate dehydrogenase
      (G6PDH) and the malic enzyme, were lower in the three n-3 PUFA groups. The
      activity of carnitine palmitoyltransferase (CPT) in mitochondria was higher only
      in the eicosapentaenoic acid group than in the other groups. The activity of
      Mg(2+)-dependent phosphatidate phosphohydrolase (PAP) in microsomes and cytosol
      was lower in the eicosapentaenoic and docosahexaenoic acid groups than in the
      linoleic acid group, while there was no effect of dietary fats on the activities
      of diacylglycerol acyltransferase (DGAT) and glycerol-3-phosphate acyltransferase
      (G3PAT) in microsomes. The CTP: phosphocholine cytidylyltransferase (CT) activity
      in the homogenate was lower in the n-3 PUFA groups, the reduction being more
      prominent in the eicosapentaenoic and docosahexaenoic acid groups than in the
      alpha-linolenic acid group. The choline kinase (CK) activity in cytosol was lower
      in the eicosapentaenoic acid group than in the linoleic acid group. These results
      showed that dietary alpha-linolenic, eicosapentaenoic and docosahexaenoic acids
      differently influenced hepatic lipogenesis and the partition of fatty acid into
      oxidation or glycerolipid synthesis.

PMID- 9614700
TI  - Purification and characterization of sulfur reductase from a moderately
      thermophilic bacterial strain, TI-1, that oxidizes iron.
AB  - A moderately thermophilic bacterium, strain TI-1, produces H2S outside of the
      cells when grown at 45 degrees C on Fe(2+)-medium (pH 1.8) containing elemental
      sulfur and L-glutamic acid. A newly identified sulfur reductase was present in
      the cytosol of this strain and was purified to an electrophoretically homogeneous
      state from strain TI-1. The apparent molecular weight of sulfur reductase was
      86,000 by gel filtration and 48,000 by SDS-PAGE, so the enzyme was a homodimer.
      The enzyme was most active at pH 9.0 and 60 to 70 degrees C, and it catalyzed the
      reduction of 1 mol of elemental sulfur with 1 mol of NADH to give 1 mol of H2S
      and 1 mol of NAD+. Elemental sulfur was a specific electron acceptor of this
      enzyme. Thiosulfate, sulfite, and tetrathionate were not electron acceptors, but
      inhibited sulfur reductase activity. NADPH was not used as an electron donor.

PMID- 9614699
TI  - Substrate specificities of alpha-L-arabinofuranosidases produced by two species
      of Aspergillus niger.
AB  - Precise substrate specificities of alpha-L-arabinofuranosidases from Aspergillus
      niger 5-16 and Aspergillus niger (Megazyme) were investigated. Both enzymes
      hydrolyzed arabinan and debranched-arabinan at almost the same rate. The alpha-L
      Arabinofuranosidase from A. niger (Megazyme) preferentially released arabinosyl
      side-chains of arabinan. The enzyme tore off both arabinoses attached to O-alpha
      L-arabinofuranosyl-(1-->3)-O-beta-D-xylopyranosyl-(1--> 4)-D-xylopyranose and O
      beta-D-xylopyranosyl-(1-->4)-[O-alpha-L- arabinofuranosyl-(1-->3)]-O-beta-D
      xylopyranosyl-(1-->4)-D-xylopyranose, but did not tear off xylosyl-arabinose from
      O-beta-D-xylopyranosyl-(1-->2)-O-alpha-L-arabinofuranosyl-(1-->3) -O-beta-D
      xylopyranosyl-(1-->4)-O-beta-D-xylopyranosyl-(1-->4)-D- xylopyranose. The enzyme
      from A. niger (Megazyme) hydrolyzed methyl 2-O-, methyl 3-O- and methyl 5-O-alpha
      L-arabinofuranosyl-alpha-L-arabinofuranosides to arabinose and methyl alpha-L
      arabinofuranoside in the order of (1-->5)->(1-->2)->(1-->3)-linkages. On the
      other hand, alpha-L-arabinofuranosidase from A. niger 5-16 successively liberated
      the arabinose of arabinan from non-reducing terminals. The enzyme hydrolyzed in
      the order of (1-->2- > (1-->3)- > (1-->5)-linkages. Both of the enzymes
      hydrolyzed the (1-->3)-linkage more than the (1-->5)-linkage of methyl 3,5-di-O
      alpha-L-arabinofuranosyl-alpha-L-arabinofuranoside.

PMID- 9614701
TI  - Prevention of peroxidative stress in rats fed on a low vitamin E-containing diet
      by supplementing with a fermented bovine milk whey preparation: effect of lactic
      acid and beta-lactoglobulin on the antiperoxidative action.
AB  - We examined the antiperoxidative properties of a fermented bovine milk whey
      preparation in rats fed on a low vitamin E-containing diet and identified the
      active principle in the preparation. An exogenous supply of either lactic acid or
      an amino acid mixture simulated the unfermented whey proteins to prevent red
      blood cell (RBC) hemolysis and to lower liver thiobarbituric acid reactive
      substances (TBARS). The supply of either whey proteins or beta-lactoglobulin
      resulted in an increase in liver GSH and prevented iron-mediated lipoprotein
      peroxidation. These protein effects were reproduced in rats orally administered
      with either GSH or its precursor, gamma-glutamylcysteine. The amount of TBARS
      formed during in vitro lipoprotein peroxidation were positively correlated with
      liver TBARS. These results suggest that fermented milk products containing lactic
      acid and bovine milk whey proteins can ameliorate peroxidative stress in tissues
      subjected to vitamin E deficiency.

PMID- 9614702
TI  - Identification of Bombyx mori midgut receptor for Bacillus thuringiensis
      insecticidal CryIA(a) toxin.
AB  - As part of a study of the mechanism by which Bacillus thuringiensis insecticidal
      crystal protein acts, a Bombyx mori receptor to the CryIA(a) toxin specific for
      lepidopterans was examined. Histological examination showed that the toxin acted
      on the brush-border membrane of the midgut columnar cells and broke its infolding
      structure, causing cell lysis. The membrane vesicles were purified, and a 175-kDa
      protein binding the toxin was found that accounted for some 0.015% of membrane
      proteins. The protein, designated BtR175, was a glycoprotein that reacted with
      concanavalin A. Anti-BtR antibodies inhibited the binding of toxin to membrane
      vesicles in vitro and decreased the effect of the toxin to silkworms in vivo.
      BtR175, although found in the gut, was not found in fat bodies, integument, or
      silk glands. These results indicated that BtR175 was the receptor protein for the
      insecticidal toxin. Proteins (137 and 107 kDa) binding the CryIA(a) toxin also
      were found in the gut membranes of Tenebrio moritor larvae, a coleopteran not
      sensitive to the toxin. The specificity of the toxin could not be explained only
      in term of the existence of its binding protein.

PMID- 9614703
TI  - Cloning, sequencing, and expression of the Bombyx mori receptor for Bacillus
      thuringiensis insecticidal CryIA(a) toxin.
AB  - Bacillus thuringiensis strains produce insect-specific Bt toxins. Bt CryIA(a)
      toxin binds to a 175-kDa glycoprotein (BtR175) on the microvillus membranes of
      columnar cells in the Bombyx mori midgut and causes lysis of the cells. BtR175
      was purified, and its cDNA was cloned. The cDNA encodes a newly identified 193.3
      kDa preproprotein form of BtR175 that includes nine extracellular cadherin
      repeats, a 23.5-kDa membrane-proximal domain, a membrane-spanning region, and a
      13.6-kDa cytoplasmic domain. Spodoptera frugiperda cells transfected with a
      recombinant baculovirus DNA carrying the cDNA produced a 175-kDa protein that
      reacted with anti-BtR antibodies and the Bt CryIA(a) toxin.

PMID- 9614704
TI  - Trehalose 6-phosphate production with energy coupling fermentation by yeast
      cells.
AB  - We tried a method for the production of trehalose 6-phosphate (T6P) with energy
      coupling fermentation by baker's yeast. T6P was produced in a reaction mixture
      containing glucose, 5'-UMP, MgSO4, inorganic phosphate, and dried cells of
      baker's yeast as the enzyme preparation, T6P was isolated from the reaction
      mixture and identified by TLC, HPLC, GC-MS, and enzymatic methods. The reaction
      conditions suitable for T6P production were investigated. The formation of T6P
      and its precursors, glucose 6-phosphate and UDPglucose, at various pHs and
      concentrations of substrates was examined. Accumulation of T6P was maximum with a
      reaction mixture containing 1 M glucose, 20 mM 5'-UMP, 20 mM MgSO4, 400 mM sodium
      phosphate buffer (pH 6.2), and 100 mg/ml dried cells of baker's yeast shaken at
      37 degrees C for 6 h. The yield of T6P as a percentage of glucose was 11%
      (mol/mol) under these reaction conditions.

PMID- 9614705
TI  - Purification, characterization, and gene analysis of catechol 2,3-dioxygenase
      from the aniline-assimilating bacterium Pseudomonas species AW-2.
AB  - Catechol 2,3-dioxygenase (C23D; EC 1.13.1.2) was purified to homogeneity from a
      cell extract of Pseudomonas sp. AW-2 grown on aniline, and the purified C23D was
      characterized. The molecular mass estimated by gel filtration was 110 kDa. The
      enzyme dissociated into four identical subunits each with the molecular mass of
      33 kDa. The enzyme had high activity for 3-methylcatechol as well as catechol,
      and differed from the enzyme from Pseudomonas putida mt-2, which carries the TOL
      plasmid, in optimal pH for catechol, extradiol cleavage activities for 3
      methylcatechol and 4-methylcatechol, and immunochemical properties. The amino
      acid sequence deduced from a C23D gene, alnE, from Pseudomonas sp. AW-2 was 85.7%
      identical to that of 3-methylcatechol 2,3-dioxygenase from toluidine-assimilating
      Pseudomonas putida UCC22. AlnE was 44.1% identical to the C23D encoded by xylE in
      P. putida mt-2. Because XylE has low activity for 3-methylcatechol, these results
      suggest that the differences in substrate specificity for 3-methylcatechol among
      the C23Ds reflected their sequence similarity.

PMID- 9614706
TI  - Molecular cloning and sequence analysis of catalase cDNA from green pepper
      seedlings elicited with arachidonic acid.
AB  - We isolated a cDNA encoding catalase from green pepper seedlings elicited with
      arachidonic acid, based on the amino acid sequences of the purified protein. The
      nucleotide sequence of the isolated cDNA contained a single open reading frame
      predicted to encode 492 amino acid residues with a calculated molecular mass of
      56439.0 daltons. The deduced amino acid sequence contained the amino acid
      sequences found by sequencing of the peptides. The total deduced amino acid
      sequence showed high similarity with those of the other plant catalases reported
      so far and was found to possess the peroxisomal targeting sequence conserved
      among plant catalases. Transcription of the catalase gene in green pepper
      seedlings was found to be induced by treatment with arachidonic acid.

PMID- 9614707
TI  - Purification and characterization of triacylglycerol lipase from Aspergillus
      oryzae.
AB  - Triacylglycerol lipase (L3) was purified from Aspergillus oryzae RIB128 by
      ammonium sulfate fractionation, acetone precipitation, anion-exchange
      chromatography, and gel filtration. The purified enzyme was formed from a
      glycoprotein and a monomeric protein with molecular masses of 25 and 29 kDa, by
      SDS-PAGE and gel filtration, respectively. The optimum pH at 40 degrees C was 5.5
      and the optimum temperature at pH 5.5 was 40 degrees C. The enzyme was stable
      between a pH range of 4.0-7.5 at 30 degrees C for 24 h, and at up to 30 degrees C
      at pH 5.5 for 1 h. Heavy metal ions, detergents, DFP, and DEP strongly inhibited
      the enzyme activity. The lipase hydrolyzed not only triacylglycerols but also
      monoacylglycerols and diacylglycerols. The enzyme had higher specificity toward
      triacylglycerols of middle-chain saturated fatty acids than short-chain or long
      chain fatty acids. The enzyme had 1,3-positional specificity. The N-terminal
      amino acid sequence of the enzyme was not significantly similar to that of other
      lipases with published sequences.

PMID- 9614708
TI  - Hypercholesterolemic effect in rats of a dietary addition of the nitric oxide
      synthase inhibitor, L-N omega nitroarginine, by less synthesis of bile acids.
AB  - We have previously reported that feeding rats with a diet containing 0.02% L-N
      omega nitroarginine (L-NNA), a specific inhibitor of nitric oxide synthase,
      induced hypercholesterolemia. This present study was conducted to examine the
      underlying mechanism for hypercholesterolemia in rats. In experiment 1, feeding a
      diet containing 0.02% L-NNA for 5 wk elevated the concentration of serum
      cholesterol and reduced the excretion of fecal bile acids, but did not affect the
      excretion of fecal neutral sterols. Reduced activity of hepatic cholesterol 7
      alpha-hydroxylase, the rate-limiting enzyme for the biosynthesis of bile acids
      from cholesterol, was observed in the rats receiving L-NNA. In experiment 2, rats
      were fed for 5 wk on a diet with or without 0.02% L-NNA that was or was not
      supplemented with 4% L-arginine. The L-NNA treatment elevated the serum
      concentrations of total cholesterol, free cholesterol and esterified cholesterol,
      and reduced the activity of hepatic cholesterol 7 alpha-hydroxylase, serum
      nitrate (a metabolite of NO) and the ratio of HDL-cholesterol versus serum total
      cholesterol. These alterations were suppressed by supplementing the L-NNA
      containing diet with L-arginine. The results suggest that lower NO production by
      L-NNA caused hypercholesterolemia by a mechanism involving impaired bile acid
      synthesis.

PMID- 9614709
TI  - In search of circular permuted variants of Escherichia coli dihydrofolate
      reductase.
AB  - A circularized form of a Cys-free mutant of Escherichia coli dihydrofolate
      reductase (DHFR) was used to search for a proteolytic site that gave new N- and C
      termini on circularized DHFR with enzyme activity. Of the six site-specific
      proteolytic enzymes tested, three proteases, Achromobacter protease I (lysine
      specific endopeptidase), asparaginylendopeptidase, and Staphylococcus aureus V8
      protease, cleaved a single site of the circularized DHFR to form circular
      permuted variants. Twenty-four possible sites for cleavage were found formation
      of eight circular permuted variants was suggested by results of N-terminal
      sequence analysis of the linearized proteins isolated by gel filtration in the
      presence of 5 M guanidine hydrochloride. Mapping of the predicted cleavage sites
      on the DHFR molecule suggested that they were not all at a specific loop and,
      therefore, there are many possible circular permuted variants.

PMID- 9614710
TI  - Purification and characterization of trehalose phosphorylase from Catellatospora
      ferruginea.
AB  - Trehalose phosphorylase was purified from the cell extracts of Catellatospora
      ferruginea. The enzyme had an apparent molecular weight of 400,000 by gel
      filtration and 98,000 by SDS-PAGE, suggesting that the enzyme was a tetramer. The
      enzyme was specific for trehalose in phosphorolysis and specific for beta-D
      glucose 1-phosphate in synthesis. In addition to D-glucose, D-xylose and D-fucose
      were also possible sugar acceptors during synthesis. Phosphate ions were a key to
      the activity and stability of the enzyme, controlling the equilibrium of the
      reversible reaction and the heat stability of the enzyme. The enzyme was strongly
      inhibited by p-chloromercuribenzoate and pyridoxal phosphate. The enzyme was
      inactivated by heat or by storage frozen with ammonium chloride and lithium
      chloride.

PMID- 9614711
TI  - A spin trap, N-tert-butyl-alpha-phenylnitrone extends the life span of mice.
AB  - To characterize the pharmacological effects of N-tert-butyl-alpha-phenylnitrone
      (PBN) on life span, we administered PBN in drinking water to 24.5-month-old mice,
      and the survivors were counted. Their water consumption and body weights were
      measured as biological markers. PBN-treated animals as compared with control
      animals had prolonged mean and maximum life spans. Their water consumption
      decreased but no significant change was found in their body weights, indicating
      that the metabolism was improved. Results showed that PBN indeed affects
      physiological functions and extends life span. We propose that nitric oxide
      release from PBN may be involved in altering the aging process.

PMID- 9614712
TI  - Purification and properties of acetylacetoin synthase from Bacillus sp. YUF-4.
AB  - In Bacillus sp. YUF-4, acetylacetoin synthase was induced by acetoin, while
      glucose inhibited the induction. The enzyme was purified 111-fold by 6
      purification steps, and a further purification followed, by HPLC using a TSK gel,
      Phenyl-5PW RP. The resulting enzyme gave a single band with a molecular mass of
      62 kDa by SDS-PAGE and 220 kDa by gel filtration. Some enzymic characteristics
      were studied.

PMID- 9614713
TI  - Need for aromatic residue at position 115 for proteolytic activity found by site
      directed mutagenesis of tryptophan 115 in thermolysin.
AB  - In thermolysin, tryptophan 115 seems to be at the S2 subsite. Trp-115 was
      replaced with tyrosine, phenylalanine, leucine, and valine during site-directed
      mutagenesis in order to evaluate the role of Trp-115 in the proteolytic activity
      of thermolysin. The mutant enzymes with Tyr-115 or Phe-115 had as much
      proteolytic activity as the wild-type enzyme, but the other two mutant enzymes
      had no activity. We found earlier that the substitution of Trp-115 with alanine,
      glutamic acid, lysine, and glutamine causes the enzyme to lose all activity, so
      an aromatic amino acid at position 115 seems to be essential for thermolysin.

PMID- 9614714
TI  - Xylooligosaccharide production by Aspergillus oryzae 13 immobilized on a nonwoven
      fabric.
AB  - Immobilized mycelia were screened for xylooligosaccharide production from xylan,
      and 20 strains of Aspergillus oryzae were selected. For its high activity and
      operational stability of xylooligosaccharides formation, immobilized A. oryzae 13
      was selected for further examination. Batch production of xylooligosaccharides
      from xylan by the immobilized mycelia was repeated a total of 4 times.

PMID- 9614715
TI  - Theanine-induced reduction of brain serotonin concentration in rats.
AB  - Following the administration of theanine, the brain tryptophan content
      significantly increased or tended to increase, but the contents of serotonin and
      5-hydroxyindole acetic acid (5HIAA) decreased. The use of inhibitors of serotonin
      metabolism enable us to speculate that theanine reduced serotonin synthesis and
      also increased serotonin degradation in the brain.

PMID- 9614716
TI  - Binding of paratropomyosin to beta-connectin from chicken skeletal muscle.
AB  - We found that paratropomyosin bound to beta-connectin, in examining binding of
      paratropomyosin at the junction of A- and I-bands of sarcomeres. The turbidity of
      a mixture of beta-connectin and paratropomyosin was greater with more
      paratropomyosin added, but high concentrations of Ca2+ suppress this increase.
      These results suggest that paratropomyosin is released from connectin filaments
      at the A-I junction region by increased concentrations of calcium ions in
      postmortem skeletal muscles.

PMID- 9614717
TI  - Complete amino acid sequence of chitinase-A from leaves of pokeweed (Phytolacca
      americana).
AB  - The complete amino acid sequence of pokeweed leaf chitinase-A was determined.
      First all 11 tryptic peptides from the reduced and S-carboxymethylated form of
      the enzyme were sequenced. Then the same form of the enzyme was cleaved with
      cyanogen bromide, giving three fragments. The fragments were digested with
      chymotrypsin or Staphylococcus aureus V8 protease. Last, the 11 tryptic peptides
      were put in order. Of seven cysteine residues, six were linked by disulfide bonds
      (between Cys25 and Cys74, Cys89 and Cys98, and Cys195 and Cys208); Cys176 was
      free. The enzyme consisted of 208 amino acid residues and had a molecular weight
      of 22,391. It consisted of only one polypeptide chain without a chitin-binding
      domain. The length of the chain was almost the same as that of the catalytic
      domains of class IL chitinases. These findings suggested that this enzyme is a
      new kind of class IIL chitinase, although its sequence resembles that of
      catalytic domains of class IL chitinases more than that of the class IIL
      chitinases reported so far. Discussion on the involvement of specific tryptophan
      residue in the active site of PLC-A is also given based on the sequence
      similarity with rye seed chitinase-c.

PMID- 9614719
TI  - Managing childhood pneumonia.

PMID- 9614718
TI  - Structure-related emission spectrometric analysis of the chemiluminescence of
      catechins, theaflavins and anthocyanins.
AB  - This study for the first time achieved an emission spectrometric analysis of the
      chemiluminescence of flavonoids in the presence of hydrogen peroxide,
      acetaldehyde and horseradish peroxidase, and revealed that the maximum emission
      wavelengths (Emax) strictly differ among catechins (E-max 630 nm), theaflavins
      (Emax 690 nm) and anthocyanins (Emax 675 nm) according to their chemical
      structures. This technique enabled the direct incorporation of dietary tea
      catechin into rat intestinal mucosal cells to be spectrometrically confirmed.

PMID- 9614720
TI  - Pantoprazole--a third proton pump inhibitor.

PMID- 9614721
TI  - Intrapleural streptokinase for empyema?

PMID- 9614722
TI  - Managing subclinical hypothyroidism.

PMID- 9614723
TI  - Modifying disease in rheumatoid arthritis.

PMID- 9614725
TI  - Managing carotid stenosis.

PMID- 9614726
TI  - Termination of first trimester pregnancy.

PMID- 9614724
TI  - Interferon beta-1A for multiple sclerosis.

PMID- 9614727
TI  - Melatonin for jet lag?

PMID- 9614728
TI  - The SOCRATES curriculum: an innovative integration of technology and theory in
      medical education.
AB  - This article describes the pilot study of an innovative medical school curriculum
      module that utilizes a modified problem-based learning (PBL) approach to teach
      medical students about management of diabetes mellitus. The PBL-based curriculum
      incorporated computer simulations and analysis of videotaped patient encounters
      in addition to independent study and group discussion. At the conclusion of the
      study, student knowledge and clinical decision-making skills were evaluated via
      questionnaires and examinations. Twenty-three students completed the workshop and
      all evaluation assessments. Students performed well on the case-study
      examinations (mean score of 3.39 out of 4) but not on the short answer essay
      examination, which assessed basic knowledge. Students rated the quality and
      appeal of the activities using Likert-type scales. In general, students perceived
      the activities as very worthwhile, with reasonable complexity and adequate time
      devoted to each activity. Students were very positive about the workshop and
      preceptor; 15 of the 16 items used to rate workshop appeal yielded mean scores
      greater than 4 (on a scale of 1 to 5, with 5 being the highest). The results of
      the pilot study suggest future enhancements that would further improve the
      outcomes of the training.

PMID- 9614729
TI  - Evaluation of two videotape instruction programmes on how to break bad news--for
      Cantonese-speaking medical students in Hong Kong.
AB  - OBJECTIVES: To evaluate a culture-specific videotape on how to 'break bad news'
      and another videotape produced by a western university, and to determine if the
      language of presentation influenced the students' perceived abilities to execute
      basic skills. SUBJECTS: Third year medical students at the Faculty of Medicine,
      the University of Hong Kong. DESIGN: Longitudinal study with experimental design.
      INTERVENTION: Two instructional tapes on breaking bad news; one using Chinese
      speaking role models and one using English. RESULTS: In both groups, self
      efficacy summed scores increased from 26.8 (95% CI = 25.9-27.7) at the pre-test
      to 29.0 (95% CI = 28.4-29.6). The biggest changes occurred in perceived self
      efficacy regarding specific skills. However, students using the Chinese tape
      rated skills as more useful than those using the English tape. CONCLUSION: The
      videotapes were useful in teaching communication skills. Culturally relevant
      audiovisual materials were more effective.

PMID- 9614730
TI  - Simulators in clinical surgery.
AB  - Simulators are no replacement for patients in surgical learning. Live patients
      are required for teaching clinical signs and skills. Large numbers of students, a
      relative lack of motivation, a decreasing number of common cases, unwilling
      patients, differences in language, etc., make clinical teaching in India a bitter
      problem. Because patient-related problems are important, surgical training using
      models can help students to gain effective control over surgical signs and
      skills.

PMID- 9614731
TI  - The legal and ethical aspects of telemedicine. 1: Confidentiality and the
      patient's rights of access.
AB  - This paper reviews the principle of confidentiality and the rights of access by
      patients to their medical records. Confidentiality has been germane to the ethics
      of medical practice since the time of Hippocrates but the nature of the legal
      obligation of confidence does not have such a clear pedigree. The introduction of
      cross-border telemedical consultations presents a very real danger to maintaining
      the confidentiality of medical data. While both the common law and statute law
      can be used to prevent the unauthorized interception and disclosure of medical
      data and protect the patient's rights of access and ownership in the UK, it is
      the harmonization regime of the European Union that will bring comprehensive
      regulation and legal clarity to the protection of patients' rights within an
      increasingly international medical 'super-specialty'.

PMID- 9614732
TI  - Telemedicine in Australia. Recent developments.
AB  - There have been a number of important developments in Australia in the area of
      telemedicine. At the national level, the House of Representatives' Standing
      Committee on Family and Community Affairs has been conducting the Inquiry into
      Health Information Management and Telemedicine. The Australian Health Ministers'
      Advisory Council has supported the establishment of a working party convened by
      the South Australian Health Commission to prepare a detailed report on issues
      relating to telemedicine. State governments have begun a number of telemedicine
      projects, including major initiatives in New South Wales and Victoria and the
      extensive development of telepsychiatry services in Queensland. Research
      activities in high-speed image transmission have been undertaken by the
      Australian Computing and Communications Institute and Telstra, and by the
      Australian Navy. The matter of the funding of both capital and recurrent costs of
      telemedicine services has not been resolved, and issues of security and privacy
      of medical information are subjects to discussion. The use of the Internet as a
      universal communications medium may provide opportunities for the expansion of
      telemedicine services, particularly in the area of continuing medical education.
      A need has been recognized for the coordinated evaluation of telemedicine
      services as cost-benefit considerations are seen to be very important.

PMID- 9614733
TI  - An economic analysis of teleconsultation in otorhinolaryngology.
AB  - A cost comparison of three different methods of providing consultations for ear,
      nose and throat (ENT) problems was carried out. The study was based on the
      delivery of ENT examination and treatment to a small primary-care centre without
      an ENT specialist in northern Norway. The three alternatives evaluated were
      teleconsultation, a visiting specialist and patient travel to the nearest
      secondary-care centre. Patient travel was cheaper for patient workloads below 56
      per year. For patient workloads above 56 and below 325 patients per year
      teleconsultation was the cheapest alternative. Above 325 patients per year, the
      visiting specialist service cost less than either teleconsultation or patient
      travel. Transfer of medical skills from the specialist to the general
      practitioner was also accounted for, separately from the main cost calculation.
      Teleconsultation then became cost-effective for patient workloads above 52
      patients per year.

PMID- 9614734
TI  - Paediatric echocardiography by telemedicine--nine years' experience.
AB  - In 1987 we established a realtime echocardiography service by telemedicine from
      the paediatric cardiology department of a tertiary-care hospital in Halifax. The
      service was initially provided to single regional hospital but was expanded to
      six regional hospitals in the three Canadian Maritime Provinces. The system used
      a dial-up broadband video-transmission service provided by the telephone
      companies. Records of all transmissions were kept prospectively and reviewed to
      January 1997. A total of 324 transmissions were made. During 1995-96 there were
      135 studies: 69 (51%) were urgent examinations of newborn children and 30 (22%)
      were urgent examinations of older children; repeat studies and postoperative
      checks (usually for pericardial effusion) accounted for the other 36 studies
      (27%). The images were of broadcast quality except in five cases where problems
      with transmission or poor sedation occurred. A comparison of 26 transmitted
      studies with repeat, 'in person' studies showed no important discrepancies in
      diagnosis. During the two-year study period, the cost of the network (equipment
      leasing costs and telecommunications costs) was C$90,000. Use of the telemedicine
      network saved unnecessary patient transfer in 31 cases. The cost of the
      transportation avoided was C$100,000-C$118,000. This review confirms our
      preliminary findings that broadband echocardiography transmission provides a
      service comparable in availability and accuracy to that provided in our
      paediatric cardiology division.

PMID- 9614735
TI  - Patient satisfaction with multispecialty interactive teleconsultations.
AB  - Satisfaction with teleconsulting was evaluated for 96 patients using the Kentucky
      TeleCare telemedicine network. Consultant specialties included psychiatry (41),
      dermatology (24), clinical nutrition (20), anaesthesia (3), infectious diseases
      (3), rheumatology (2), internal medicine (1), neurology (1) and paediatric
      pulmonology (1). The results indicated a high level of patient satisfaction, with
      a mean score of 6.8 (on a 7-point Likert scale with 1 = strongly disagree and 7 =
      strongly agree) for the question 'Overall, I was very satisfied with today's
      consultation'. The results indicated that the majority of patients were satisfied
      with the telemedicine encounter although a minority, 16%, would have preferred to
      have seen the specialist in person.

PMID- 9614736
TI  - The effect of transmission bandwidth on diagnostic accuracy in remote fetal
      ultrasound scanning.
AB  - Six subspecialists with considerable experience in fetal ultrasound viewed a
      selection of pre-recorded ultrasound scans. Scans from 18 patients recorded on
      VHS video-tape were supplied from five centres in the UK and Ireland, each made
      on a high-resolution ultrasound machine by an experienced sonologist at a
      referral centre. Each observer viewed the scans on a large display monitor in an
      individual viewing booth. The scans were viewed in random order, at randomly
      selected bandwidths. Observers, who were blinded to both recording and bandwidth,
      assessed the technical quality on a five-point Likert scale. They also recorded
      their diagnosis. The six observers each carried out 32 viewing sessions, which
      gave a total of 192 viewings. There was no significant difference in the
      perceived technical quality of the scans between the two bandwidths used (P =
      0.09). Of the 84 recordings transmitted at 1920 kbit/s, 71 (85%) were diagnosed
      correctly or 'half correctly' and 13 (15%) were misdiagnosed. Of the 95
      recordings transmitted at 384 kbit/s, 66 (69%) were diagnosed correctly or 'half
      correctly' and 29 (31%) were misdiagnosed. This difference was significant (P =
      0.03). The results indicate that although there were no perceived differences in
      technical quality between recordings transmitted at 384 or 1920 kbit/s,
      diagnostic accuracy was marginally worse at the lower bandwidth. This suggests
      that the higher bandwidth conveys more detail and information to the observer,
      which in turn enables more accurate diagnosis. However, further work is required
      before a definitive choice can be made about the optimum transmission bandwidth
      for remote fetal ultrasound studies.

PMID- 9614737
TI  - Successful development of telemedicine systems--seven core principles.
AB  - This article discusses seven core principles that underlie the development of
      successful telemedicine systems. These principles have been formulated from
      evidence in the literature and from the personal experience of setting up three
      telemedicine systems in Australia. Of particular importance has been the
      observation of failed telemedicine systems, of which there are many examples in
      the world literature. It is important to learn from history by studying both the
      successful and the unsuccessful components of these programmes. Telemedicine is
      still a relatively new area of interest, and while the technology is rapidly
      evolving, changing and fascinating, it is still the human factors that tend to
      determine the success or failure of telemedicine projects. These cannot be
      ignored.

PMID- 9614738
TI  - The use of telemedicine to perform psychiatric assessments under the Mental
      Health Act.

PMID- 9614739
TI  - Telemedicine in the follow-up of corneal transplant patients.

PMID- 9614740
TI  - Gastric emptying of solids measured by means of magnetised iron oxide powder.
AB  - The aim of this study was to develop a radiation-free method to measure gastric
      emptying. Such a method would be useful e.g. for patients who need repeated
      measurements and in pregnancy. Ferrimagnetic particles (gamma-Fe2O3), ingested
      within a solid test meal (pancakes), were magnetised by an applied magnetic
      field. After magnetisation, the remanent magnetic field was measured with
      fluxgate magnetometers outside the stomach (anterior and posterior). The
      intragastric contents was estimated from the strength of the remanent field. The
      procedure was repeated 18 times over a period of up to 2 h postprandially. The
      test meal was chosen to correspond to a radiolabelled test meal that had
      previously been used in a scintigraphic study with (other) healthy persons. In
      vivo measurements were carried out on 16 healthy male volunteers. The estimated
      retained magnetic tracer in the stomach after the 2 h measurement time was 31 +/-
      12% (mean +/- SD) and the lag phase time was 31 +/- 11 min. The corresponding
      scintigraphic curve (from the previous study) from 16 males showed 40 +/- 14%
      retained isotope after 2 h. The early part of the mean emptying curve decreased
      slightly faster than the corresponding scintigraphic one, but the similarity of
      the two seems promising enough for further development of the present method.

PMID- 9614741
TI  - Computer simulation of the impact of different dimensions of the stomach on the
      validity of electrogastrograms.
AB  - The impact of the dimensions of the stomach on cutaneous recordings of gastric
      electrical activity (GEA) has not been adequately studied. The stomach was
      represented as a truncated conoid in a spherical coordinate system. The gastric
      electric field was modelled using a previously described methodology. Electrical
      potentials were calculated from sets of points simulating standard cutaneous
      recordings. The frequency of the signals was maintained at 3 cycles min-1 (period
      of repetition: 20 s), while the velocity of propagation of the depolarisation
      waves was reduced relative to the reduction in gastric dimensions. The signals
      were digitally contaminated with a random artificial artefact with a constant
      amplitude range of 0.2 mV, while the dimensions of the conoid (the
      circumferential radii and the length of the central axis) were decreased by
      factors of 1.5, two, four, six and eight. Simulated EGG signals were evaluated
      quantitatively. Simulated EGG records contaminated with random signals recorded
      from stomachs with decreasing dimensions exhibited non-linearly increasing
      standard deviations (p < 0.001). Randomly contaminated EGGs calculated from
      stomachs with dimensions reduced four, six and eight times were abnormal
      according to previously established quantitative criteria. Computer modelling
      indicated that gastric dimensions can significantly influence the validity of
      EGGs. These findings could be particularly important in a paediatric
      electrogastrography.

PMID- 9614742
TI  - Linear servo-controlled pressure generator for forced oscillation measurements.
AB  - In respiratory input impedance measurements, the low-frequency range contains
      important clinical and physiological information. However, the patient's
      spontaneous ventilation can contaminate the data in this range, leading to
      unreliable results. Unbiased estimators are a good alternative to overcome this
      problem, provided that the generator is considered linear. This condition is not
      fulfilled by most existing generators as they are based on loudspeakers, which
      have strong nonlinearities. The present work aims to contribute to the solution
      of this problem, and describes a pressure generator that minimises the
      nonlinearities by an optical sensor placed in a position feedback loop. The
      static evaluation shows a high linearity for the optical system. The well known
      frequency response of pressure transducers is used in the dynamic evaluation of
      the instrument. The analysis of the generator shows that the use of position
      feedback improved the frequency response. The total harmonic distortion (THD)
      measurement shows that closed loop resulted in an effective decrease in the
      nonlinearities. The reduction of THD achieved by the servo-controlled generator
      can contribute to the practical implementation of the unbiased estimators,
      increasing the reliability of the impedance data, especially in the low-frequency
      range. This system is compared with conventional generators and with another
      servo-controlled system.

PMID- 9614743
TI  - Hot-wire anemometer for spirography.
AB  - The use of a constant temperature hot-wire anemometer flow sensor for spirography
      is reported. The construction, operating principles and calibration procedure of
      the apparatus are described, and temperature compensation method is discussed.
      Frequency response is studied. It is shown that this hot-wire flow transducer
      satisfies common demands with respect to accuracy, response time and temperature
      variations.

PMID- 9614744
TI  - Cardiokymograph system with a capacitance transducer and its preliminary
      application in the measurement of heart wall movement.
AB  - A novel cardiokymograph system is introduced. The new system features a
      capacitance transducer with increased sensitivity and can be used in multichannel
      measurements. The novelty of this technique is the injection of a current into
      the patient coupled with the use of a capacitive displacement transducer and the
      possibility of multichannel monitoring. It provides for the possibility of
      removing breath noise when some signal processing technique, such as adaptive
      filtering, is used. Further investigation is needed to demonstrate clinical
      significance and pathologies.

PMID- 9614745
TI  - Quantifying electrocardiogram RT-RR variability interactions.
AB  - A dynamic linear parametric model is designed to quantify the dependence of
      ventricular repolarisation duration variability on heart period changes and other
      immeasurable factors. The model analyses the beat-to-beat series of the RR
      duration and of the interval between R- and T-wave apexes (RT period). Directly
      from these two signals, a parametric identification procedure and spectral
      decomposition techniques allow RT variability to be divided into RR-related and
      RR-unrelated parts and allow the RT-RR transfer function to be calculated. RT
      variability is driven by RR changes at low frequency (LF, around 0.1 Hz) and high
      frequency (HF, at the respiratory rate), whereas, at very low frequencies, the RR
      unrelated contribution to the total RT variability is remarkable. During tilt at
      LF the RR-related RT percentage power increases (p < 0.02), the RR-unrelated RT
      percentage power remains unchanged, the gain of the RT-RR relationship largely
      increases (p < 0.001), and the phase is not significantly modified. Both the RR
      related and the RR-unrelated RT percentage powers at LF are not affected by
      controlled respiration, and an increase in the RT-RR gain at HF is observed (p <
      0.02). The proposed analysis may help to describe the regulation of the
      ventricular repolarisation process and to extract indexes quantifying the
      coupling between heart period and ventricular repolarisation interval changes.

PMID- 9614746
TI  - Performance assessment of standard algorithms for dynamic R-T interval
      measurement: comparison between R-Tapex and R-T(end) approach.
AB  - Three automatic approaches to ventricular repolarisation duration measurement (R
      Tapex, R-T(end threshold) and R-T(end fitting) methods) are compared on computer
      generated and real ECG signals, in relation to their reliability in the presence
      of the most common electrocardiographic artefacts (i.e. additive broadband noise
      and additive and multiplicative periodical disturbances). Simulations permit the
      evaluation of the amount of R-T beat-to-beat variability induced by the
      artefacts. The R-T(end threshold) method performs better than the R-T(end
      fitting) one, and, hence, the latter should be used with caution when R-T(end)
      variability is addressed. Whereas the R-Tapex method is more robust with regard
      to broadband noise than the R-T(end threshold) one, the reverse situation is
      observed in the presence of periodical amplitude modulations. A high level of
      broadband noise dose not prevent the detection of the central frequency of
      underlying R-T periodical changes. Comparison between the power spectra of the
      beat-to-beat R-T variability series obtained from three orthogonal ECG leads
      (X,Y,Z) is used to assess the amount of real and artefactual variability in 13
      normal subjects at rest. The R-Tapex series displays rhythms at high frequency
      (HF) with a percentage power on the Z lead (57.1 +/- 4.9) greater than that on
      the X and Y leads (41.9 +/- 4.6 and 46.1 +/- 4.9, respectively), probably because
      of respiratory-related artefacts affecting the Z lead more remarkably. More
      uniform HF power distributions over X,Y,Z leads are observed in the R-T(end
      threshold) series (31.8 +/- 3.8, 39.2 +/- 4.1 and 35.1 +/- 4.2, respectively),
      thus suggesting minor sensitivity of the R-T(end threshold) measure to
      respiratory-related artefacts.

PMID- 9614747
TI  - Continuous arterio-venous haemodiafiltration: hydraulic and diffusive
      permeability index of an AN-69 capillary haemofilter.
AB  - The dependence of uraemic solute clearance on the hydraulic and diffusive
      permeability index of an AN-69 capillary haemofilter is investigated during the
      treatment of patients with continuous arterio-venous haemodiafiltration (CAVHD).
      A mathematical model is presented to calculate solute clearance and the hydraulic
      and diffusive permeability index parameters from clinical data and to predict the
      blood flow rate entering the extra-corporeal circuit from the manufacturer's
      specifications and blood viscosity. By measuring the flow rates, the patient's
      mean arterio-venous pressure difference and uraemic solute clearance under
      different clinical and operational conditions, mathematical model equations are
      evaluated. During the average survival time of an AN-69 capillary haemofilter of
      about five days, it is found that both the hydraulic permeability index and the
      diffusive permeability index decline over treatment time, independent of the
      haemofilter resistance to blood flow. The measured haemofilter resistance to
      blood flow is three times higher than the haemofilter resistance predicted from
      the manufacturer's specifications and blood viscosity. Predicting the blood flow
      rate entering the extra-corporeal circuit from the arterial haematocrit, plasma
      protein concentration and temperature and the manufacturer's specifications is
      not reliable.

PMID- 9614748
TI  - Ultrasonic determination of the elastic modulus of human cortical bone.
AB  - The elastic modulus (Cii) of the cortical bones of 19 individuals (14 femurs and
      16 tibias, fixed in formalin) was determined ultrasonically. Elastic moduli were
      measured at four anatomical positions (anterior, posterior, medial and lateral)
      and in all three planes of orientation (transverse, longitudinal and radial). The
      mean tibial Cii (34.11 GPa) was greater than that obtained for femurs (32.52
      GPa). The tibial longitudinal plane Cii (34.1 GPa) was significantly greater than
      the femoral longitudinal plane Cii (32.5 GPa). Cii was significantly higher in
      the tibia than the femur in both the medial and posterior anatomical positions.
      The anterior tibia had a significantly lower C11 compared to other positions. Cii
      was significantly higher in the longitudinal plane than the transverse or radial
      planes in both the femur and the tibia. There was no consistent difference in
      modulus between left and right sides. No age effects were observed. There were no
      significant differences between males and females, or between African Americans
      and European Americans.

PMID- 9614749
TI  - Ultrasonic characterisation in determining elastic modulus of trabecular bone
      material.
AB  - The pulse transmission ultrasonic technique is used to characterise the actual
      pathway and the wavelength dependence in relation to the bone specimen and
      microstructural dimensions. The average velocity through individual trabecular
      bone is 2901 m s-1 (SD 161), and the mean velocity through cylindrical cancellous
      bone specimens is 2717 m s-1 (SD 171). Thus, the velocity through cylindrical
      cancellous bone specimens is underestimated by as much as 6.4% of that through
      individual trabeculae. There is a statistically significant difference in the
      ultrasonic velocity between individual trabeculae and cylindrical cancellous bone
      specimens (p = 0.0012).

PMID- 9614750
TI  - CT analysis of the use of the electrical impedance technique to estimate local
      oedema in the extremities in patients with lymphatic obstruction.
AB  - The aim of the study is to establish the validity of the use of the electrical
      impedance technique for estimating local oedema in extremities through comparison
      with computed-tomography (CT) analysis. Eight healthy women (group 1) and nine
      women with unilateral leg oedema following chronic lymphatic obstruction (group
      2) are examined sequentially utilising both methods. 'Equivalent resistivities'
      of extra- and intracellular fluid (RE and RI) are measured in the leg's upper
      portion with a multi-frequency impedance meter, and seven CT slices are taken in
      the same leg segments. In each slice, the ratios of interstitial fluid to
      subcutaneous tissue and to muscle are calculated using the CT number of plasma
      for interstitial fluid, and CT numbers of subcutaneous tissue and muscle of group
      1 for 'normal' tissues. A decrease in RE and an increase in RI/RE, indicating
      extracellular fluid increase, are observed in oedematous legs in group 2 when
      compared with the left legs in group 1. Correspondingly, an increase in the
      ratios of interstitial fluid to subcutaneous tissue area and to total cross
      sectional area is observed in the oedematous legs when compared with those of
      normal legs in CT analysis. Thus the multi-frequency impedance technique is
      effective in detecting local oedema in extremities.

PMID- 9614751
TI  - Transverse tripolar stimulation of peripheral nerve: a modelling study of spatial
      selectivity.
AB  - Various anode-cathode configurations in a nerve cuff are modelled to predict
      their spatial selectivity characteristics for functional nerve stimulation. A 3D
      volume conductor model of a monofascicular nerve is used for the computation of
      stimulation-induced field potentials, whereas a cable model of myelinated nerve
      fibre is used for the calculation of the excitation thresholds of fibres. As well
      as the usual configurations (monopole, bipole, longitudinal tripole, 'steering'
      anode), a transverse tripolar configuration (central cathode) is examined. It is
      found that the transverse tripole is the only configuration giving convex
      recruitment contours and therefore maximises activation selectivity for a small
      (cylindrical) bundle of fibres in the periphery of a monofascicular nerve trunk.
      As the electrode configuration is changed to achieve greater selectivity, the
      threshold current increases. Therefore threshold currents for fibre excitation
      with a transverse tripole are relatively high. Inverse recruitment is less
      extreme than for the other configurations. The influences of several geometrical
      parameters and model conductivities of the transverse tripole on selectivity and
      threshold current are analysed. In chronic implantation, when electrodes are
      encapsulated by a layer of fibrous tissue, threshold currents are low, whereas
      the shape of the recruitment contours in transverse tripolar stimulation does not
      change.

PMID- 9614752
TI  - Robust supervised classification of motor unit action potentials.
AB  - A certainty-based classification algorithm is described, which comprises part of
      a clinically used EMG signal decomposition system. This algorithm classifies a
      candidate motor unit action potential (MUAP) to the motor unit potential trian
      (MUAPT) that produces the greatest estimated certainty, provided this maximal
      certainty is above a given threshold. The algorithm is iterative, such that the
      certainty with which assignments are made increases with each pass through the
      data, and it has specific stopping criteria. The performance and sensitivity (to
      the assignment threshold) of the Certainty algorithm and an iterative minimum
      Euclidean distance (MED) algorithm are compared by classifying sets of MUAPs
      detected in real concentric needle-detected EMG signals, using a range of
      assignment thresholds for each algorithm. With regard to MUAP assignment and
      error rates, the Certainty algorithm consistently provides better mean results
      and, more importantly, less variable results than the MED algorithm. The
      Certainty algorithm can provide mean assignment and error rates of 80.8 and 1.5%,
      respectively, with a maximum error rate of 3.2%; the MED algorithm can provide
      mean assignment and error rates of 80.3 and 3.3%, respectively, with a maximum
      error rate of 6.5%. The Certainty algorithm is relatively insensitive to the
      certainty threshold used, can consistently differentiate between similarly shaped
      MUAPs from different MUAPTs, and can make correct classifications despite
      biological shape variability, background noise and signal shape nonstationarity.

PMID- 9614753
TI  - New method for the analysis of multiple positron emission tomography dynamic
      datasets: an example applied to the estimation of the cerebral metabolic rate of
      oxygen.
AB  - Positron emission tomography (PET) provides the ability to extract useful
      quantitative information not available through other radiological techniques. In
      certain studies, the physiological parameters of interest cannot be determined
      from the data obtained from a single PET experiment alone. In this case, multiple
      experiments are required. At present, the methods used to analyse measurements
      acquired from multiple experiments often involve considering them separately
      during the modelling procedures. These methods of analysis may cause errors to be
      propagated through successive modelling procedures and do not fully utilise the
      information content provided by the PET measurements. A new method is presented,
      based on linear least squares for the analysis of PET dynamic data acquired from
      multiple experiments. This method simultaneously considers the complete set of
      measurements obtained and provides reliable parameter estimates. The efficient
      use of the information content provided by multiple experiments is considered and
      the propagation of errors is discussed. To facilitate our discussion, we apply
      this new method to the estimation of the cerebral metabolic rate of oxygen and
      the parameters of the oxygen utilisation model as a practical example. The
      results demonstrate a significant improvement in the reliability and estimation
      accuracy of the estimates for this new method. Furthermore, this method reduced
      the likelihood of errors being propagated. Therefore, the proposed method is
      suitable for the analysis of multiple PET dynamic datasets.

PMID- 9614754
TI  - Biological effects of static magnetic fields on the microcirculatory blood flow
      in vivo: a preliminary report.
AB  - There have been few studies of the effect of static magnetic fields on
      microcirculatory haemodynamics in vivo. The rat skinfold transparent chamber
      technique was used, which provides an excellent means of observing and
      quantifying direct in vivo microvascular haemodynamic responses to static
      magnetic fields up to 8 T. An intravital videomicroscope was used to measure the
      changes in blood flow before and after exposure to a magnetic field for 20 min in
      a horizontal type superconducting magnet with a bore 100 mm in diameter and 700
      mm long. After exposure, microcirculatory blood flow showed an initial increase
      for about 5 min followed by a gradual decrease and a return to the control value.
      It is hypothesised that these changes represent rebound hyperaemia following
      reduced blood flow during exposure.

PMID- 9614755
TI  - Comparative quantification of gastric electrical activity and electrogastrograms.
AB  - The aim of this study was to compare quantitatively the variability of gastric
      electrical activity (GEA) recorded from asymptomatic patients with implanted
      serosal electrodes and patients with implanted and cutaneous electrodes. Three
      pairs of electrodes were inserted into the gastric wall in six patients
      undergoing laparotomy for other reasons. Normal GEA was assessed visually once
      patients were tolerating a normal diet. Mean frequency (MF) values of the GEA
      signal in successive 256 s intervals were obtained. Standard deviations of the MF
      values for each separate channel of each patient were calculated. Probability
      density functions (pdfs) of these values were also obtained and compared. 36 1 h
      simultaneous recordings were made for three patients with implanted and cutaneous
      electrodes. The recordings were assessed both visually and with computer. A fast
      Hartley transform was used to obtain the dominant MF values in 256 s time
      intervals. These values were statistically evaluated for each channel. Normal
      internal GEA had a mean frequency of 2.5-3.75 cycles min-1 (cpm) and a standard
      deviation range of 0-0.45 cpm. Bell-shaped pdfs with coinciding maxima were
      observed in all these recordings, indicating normal electrical coupling. In the
      comparative 36 h study, using the above definitions of normality, different
      cutaneous recordings were found to reflect GEA with a sensitivity of 94% and a
      specificity of 79%.

PMID- 9614756
TI  - Dynamic model of airway pressure drop.
AB  - A multipath model of the mechanical behaviour of healthy lungs subject to a
      plethysmographic test (close to quiet breathing conditions) has been developed,
      which includes the main physiological nonlinearities. This model is built on a
      symmetric branching scheme based on Weibel's data, and uses non-linear fluid
      equations for the upper and lower airways. The alveolar gas compression, the
      changes in airway dimensions related to lung volume and/or transmural pressure,
      and the respiratory swings in glottic aperture have been taken into account. As
      clinically observed, the behaviour of the lungs, taken as a whole, seems linear,
      but it is confirmed by simulation that this linearity is only apparent.
      Simplifications and linearisations therefore need to be made carefully, only
      after their impact on the global behaviour of the lung is evaluated.

PMID- 9614757
TI  - Fast 3D registration of MR brain images using the projection correlation
      registration algorithm.
AB  - Cross-correlation can be used to match 2D images in translation and in rotation.
      An extension to 3D mono-modality matching is presented. This process allows
      comparison of two sets of data along the same orientation. To decrease
      computation time, oblique projections of a 'wandering slice' are used. The
      precision is about +/- 0.2 degree in rotation and +/- 0.2 mm in translation. Some
      examples, applied to pre- and post-therapy comparison, are given.

PMID- 9614758
TI  - Estimation of myocardial glucose utilisation with PET using the left ventricular
      time-activity curve as a non-invasive input function.
AB  - The validation study is described of a new modelling method that has been
      developed, using tracer kinetic modelling with positron emission tomography (PET)
      to achieve non-invasive measurement of myocardial metabolic rate of glucose
      (MMRGlc). Eight data sets obtained from dynamic cardiac PET 2-[18F]fluoro-2-deoxy
      D-glucose (FDG) studies on human subjects are employed, and the estimation of
      MMRGlc using both the new and traditional methods is compared. The results from
      all eight human FDG studies are consistent with those from previous computer
      simulations. With the new method, the estimated mean of K (a parameter directly
      proportional to MMRGlc) increases by about 8%, and that of k 4 (the rate constant
      of FDG dephosphorylation) decreases by about 48%. The approach should be more
      suitable for use in dynamic cardiac PET studies when non-invasive means are used
      to obtain the plasma time-activity curve from left-ventricle PET images.

PMID- 9614759
TI  - Exercise tricycle for paraplegics.
AB  - The work describes a tricycle that can be used by paraplegics without assistance.
      Paraplegics can get on and off the tricycle independently, using hydraulic
      adjustment of the saddle height. The two rear wheels can be swivelled with
      adjustable hydraulic damping, which avoids the stability problems of a standard
      tricycle when riding around bends. The principal driving power is assumed to be
      provided by functional electrical stimulation of the femoral muscles. A hub motor
      is integrated in the front wheel to increase the radius of action, as additional
      drive for cycling up gradients and in case muscle force is not sufficient. The
      desired drive power is adjusted by a throttle grip on the handlebar. The
      percentage of motor power can also be adjusted. The force applied to the pedal,
      the absolute angular position of the crank, and the angular velocity of the front
      wheel are continuously measured by a force measurement pedal and a goniometer.
      Based on this information, the motor and the functional electrical stimulation of
      the legs are controlled.

PMID- 9614760
TI  - Effect of flow direction on the morphological responses of cultured bovine aortic
      endothelial cells.
AB  - The effect of flow direction on the morphology of cultured bovine aortic
      endothelial cells is studied. Fully confluent endothelial cells cultured on glass
      were subjected to a fluid-imposed shear stress of 2 Pa for 20 min and 24 h using
      a parallel plate flow chamber. Experiments on shear flow exposure were performed
      for (i) one-way flow, (ii) reciprocating flow with a 30 min interval and (iii)
      alternating orthogonal flows with a 30 min interval. After flow exposure, the
      endothelial cells were fixed and F-actin filaments were stained with rhodamine
      phalloidin. Endothelial cells were observed and photographed by means of a
      microscope equipped with epifluorescence optics. The shape index (SI) and angle
      of cell orientation were measured, and F-actin distributions in the cells were
      statistically studied. Endothelial cells under the one-way flow condition showed
      marked elongation (SI = 0.39 +/- 0.16, mean +/- S.D.) and aligned with the flow
      direction. In the case of the reciprocating (SI = 0.63 +/- 0.14) and the
      alternating orthogonal flows (0.64 +/- 0.14), cells did not elongate so strongly
      as in the case of one-way flow. Although most cells in the reciprocating flow
      aligned with the flow direction, the cell axes in the alternate orthogonal flow
      distributed around a mean value of -45.1 degrees with a large S.D. value.
      Endothelial cells can be expected to recognise the flow direction, and change
      their shape and F-actin structure.

PMID- 9614761
TI  - Investigation into the tensile properties of collagen/chondroitin-6-sulphate
      gels: the effect of crosslinking agents and diamines.
AB  - Artificial skin substitutes based on autologous keratinocytes are being developed
      for grafting onto burns patients. In order to be used successfully in the clinic,
      these skin substitutes need to have sufficient strength to allow ease of
      handling. This may be achieved by crosslinking the collagen substratum on which
      the cells are cultured. The influence of potential crosslinking agents on the
      tensile properties of acellular collagen gels has been investigated, including
      the glycosaminoglycan, chondroitin-6-sulphate (Ch6SO4), the water-soluble
      carbodiimide crosslinking agents 1-ethyl-3-(3-diaminopropyl) carbodiimide (EDAC),
      and 1,1-carbonyldiimidazole (CDI), and the polyamines, putrescine and
      diaminohexane. Values for Young's modulus, maximum load, stress, displacement and
      percentage strain at maximum load were generated by subjecting the samples to a
      tear propagation test. Incorporation of 20% Ch6SO4 into collagen gels caused a
      significant increase in the Young's modulus, maximum load and stress at maximum
      load. Crosslinking treatment with EDAC, CDI or polyamines had little further
      benefit, and in many cases resulted in a decrease in particular parameters. In
      terms of mechanical strength, the best crosslinking combination proved to be the
      combination of CDI and diaminohexane, with results either improved or maintained
      when compared with the control no treatment variants. However, previous
      experience suggests that the use of CDI as a crosslinking reagent may inhibit
      infiltration and proliferation of fibroblasts in the substratum and it may be
      necessary to reach a compromise to obtain the best combination of biological and
      mechanical properties for artificial skin substitutes.

PMID- 9614762
TI  - Microstamp patterns of biomolecules for high-resolution neuronal networks.
AB  - A microstamping technique has been developed for high-resolution patterning of
      proteins on glass substrates for the localisation of neurons and their axons and
      dendrites. The patterning process uses a microfabricated polydimethylsiloxane
      stamp with micrometer length features to transfer multiple types of biomolecules
      to silane-derivatised substrates, using glutaraldehyde as a homobifunctional
      linker. To test the efficacy of the procedure, substrates are compared in which
      poly-d-lysine (PDL) was physisorbed and patterned by photoresist with those
      stamped with PDL. Fluorescein isothiocyanate labelled poly-l-lysine was used to
      verify the presence and uniformity of the patterns on the glass substrates. As a
      biological assay, B104 neuroblastoma cells were plated on stamped and physisorbed
      glass coverslips. Pattern compliance was determined as the percentage of cells on
      the pattern 8 h after plating. Results indicate that the stamping and photoresist
      patterning procedure are equivalent. Substrates stamped with PDL had an average
      pattern compliance of 52.6 +/- 4.4%, compared to 54.6 +/- 8.1% for physisorbed
      substrates. Measures of background avoidance were also equivalent. As the
      procedure permits successive stamping of multiple proteins, each with its own
      micropattern, it should be very useful for defining complex substrates to assist
      in cell patterning and other cell guidance studies.

PMID- 9614763
TI  - The wrath of demos.

PMID- 9614764
TI  - Effect of forward rapidly rotating shift work on circadian rhythms of arterial
      pressure, heart rate and oral temperature in air traffic controllers.
AB  - Twenty-four-hour records of arterial pressure (AP), heart rate (HR), oral
      temperature (OT) and physical and mental performance were obtained in air traffic
      controllers during morning (n = 16), afternoon (n = 17) and night (n = 19)
      shifts. Data were analyzed by the cosinor method. The results obtained during the
      morning shift were as follows (mesor/amplitude/acrophase): systolic AP (mm Hg)-
      113.6/10.0/16:03 h; diastolic AP--71.1/8.2/15:19 h; mean AP--85.6/8.8/15:41 h; HR
      (beats/min)--77.5/8.9/16:00 h; OT (dg C)--36.71/0.21/15:49 h; right-hand grip
      strength (kg)--49.8/2.0/17:43 h; left-hand grip strength--46.1/2.0/16:08 h;
      mental performance (calculations/min)--14.9/1.1/16:39 h. During the night shift
      either no change of the circadian acrophases (HR, right-hand grip strength) or
      acrophase delays ranging from about 2 h (systolic AP, OT, mental performance) up
      to 3 h (diastolic and mean AP, left-hand grip strength) were observed. Our data
      suggest that the shift system studied does not significantly alter the circadian
      rhythms, and does not induce a desynchronization, particularly as concerns
      arterial pressure and oral temperature.

PMID- 9614765
TI  - Manager or medic: the role of the occupational health professional.
AB  - Occupational health professionals originate from either the medical or the
      nursing professions (both traditional areas with their own established codes of
      practice) and work in an industrial setting alongside, for instance, managers,
      who also have an established, if different code of practice. Occupational health
      professionals are therefore confronted with the task of integrating their medical
      role within a managerial context. This paper aims to explore how occupational
      health professionals overcome the problems inherent in balancing medical with
      managerial values.

PMID- 9614766
TI  - The impact of influenza and influenza-like illness on productivity and healthcare
      resource utilization in a working population.
AB  - Four hundred and eleven subjects who either reported to Occupational Health at
      onset of influenza or influenza-like illness (I/ILI) symptoms or on return to
      work completed questionnaires on entry to the study and after 28 days. On average
      they were incapacitated or confined to bed for 2.4 days, missing 2.8 days from
      work per episode of illness. On return to work, they reported reduced
      effectiveness and inability to resume normal activity until a mean 3.5 days after
      the onset of symptoms. Each participant reported a mean of 6.5 I/ILI symptoms.
      There was a positive correlation between the number of symptoms and bed days (r =
      0.24) and missed work days (r = 0.18). There was a positive correlation between
      the number of healthcare contact and the number of reported symptoms (r = 0.23).
      A relatively high level of contact with general practitioners and pharmacists was
      observed and there was substantial use of both prescription and over-the-counter
      medication. In conclusion, the impact of I/ILI on productivity in a working
      population and the resultant cost to employers and employees may be considerable.

PMID- 9614767
TI  - Nasal challenge test in the diagnosis of allergic respiratory diseases in
      subjects occupationally exposed to a high molecular allergen (flour).
AB  - The objective of this study was the evaluation of the usefulness of the nasal
      challenge test in the diagnosis of allergic respiratory diseases in subjects
      occupationally exposed to flour. A single-blind, placebo controlled study was
      conducted in 100 subjects with occupational atopic asthma with rhinitis. The
      control groups consisted of 20 atopic subjects not sensitized to investigated
      allergens and 20 healthy subjects. A 'nasal pool' technique was used to evaluate
      the changes of the cellular response and protein level in nasal washings after
      topical provocation with allergen or placebo. The concentrations of eosinophil
      cationic protein and mast cell-derived tryptase in nasal fluid were evaluated in
      60 cases. There were significant increases in eosinophil and basophils number,
      albumin/total protein ratio, eosinophil cationic protein and tryptase levels in
      occupationally sensitized patients challenged with specific allergens. There were
      neither severe bronchial reactions or an increase of bronchial hyperreactivity in
      occupationally sensitized patients after the nasal provocation with flour. The
      nasal challenge test appears to be a very useful and safe tool for diagnosing
      occupational allergy.

PMID- 9614768
TI  - Meta-analysis and occupational epidemiology.
AB  - Meta-analysis is increasingly appearing in the epidemiologic literature. Although
      originally performed in the context of experimental or randomized controlled
      study designs and with regard to problems that are amenable to these designs, the
      method has also been applied to studies in observational epidemiologic settings.
      This movement has generated considerable debate about the validity of meta
      analysis in observational studies, which can be said to be rather shaky. Meta
      analysis is also appearing in occupational epidemiology, and a recent application
      to studies of industrial cohorts exposed to organic solvents has illustrated many
      of the arguments against meta-analysis of observational study. The propensity of
      meta-analysis for disarming critical approaches to individual study methods such
      as the standardized morbidity or mortality ratio (SMR) as effect measure, and to
      application of commonly used biostatistical techniques is illustrated. A
      cautionary note is sounded.

PMID- 9614769
TI  - Rationalization as a key stressor for public sector employees: an organizational
      case study.
AB  - Public sector organizations throughout Europe have been subject to cuts in
      Government spending, allied to demands for enhanced efficiency and effectiveness.
      Consequently, many have embarked upon radical programmes of change which
      potentially have an adverse effect upon the psychological well-being of
      employees. This study aimed to assess linkages between organization change and
      the psychological well-being of employees within the Swedish social insurance
      organization Forsakringskassan. A case study approach was adopted for the
      investigation which was carried out within the Halland region between February
      and June 1995. A questionnaire which included the Cultural Audit and the General
      Well Being Questionnaire was distributed to the organization's 456 employees in
      Halland. Questionnaire were returned by 246 employees (54.6%), reflecting the
      employment structure of the organization. The findings revealed that many issues
      associated with the process of rationalization and change were of concern to
      employees. Statistical analyses revealed that these were linked to their
      relatively high levels of 'anxiety' and their symptoms of being 'worn out'. This
      study indicates that the process of organization change is stressful for
      employees within Forsakringskassan. As public sector organizations throughout
      Europe are subject to similar pressure and are being forced to embark upon change
      programmes, it is suggested that they take cognizance of the findings of this
      investigation when making decisions regarding the planning and implementation of
      organization change.

PMID- 9614770
TI  - Headache and blood pressure among triethylamine-exposed foundry workers.
AB  - This study attempted to determine whether cold box core makers exposed to
      triethylamine in foundries experienced headaches or had elevated blood pressure
      more often than workers without TEA exposure, as proposed by earlier reports.
      Forty-one core makers in three foundries and 82 referents were interviewed
      according to a structured questionnaire, and their blood pressure was measured.
      TEA exposure was determined from breathing-zone measurements. The 8-h time
      weighted average TEA exposure varied between 0.3-60 mg/m3. The core makers did
      not report that they had the general symptoms of headaches more often than the
      referents. However, they had mild weekly headaches more often (44% vs. 17%). The
      core makers also reported headaches more often during the workweeks (45% vs.
      19%). It seems likely that TEA exposure provokes mild headache among persons
      prone to suffer from vascular headaches. There was no difference in the
      occurrence of severe headaches or in the duration of headaches between the
      groups. The blood pressures were similar in both groups.

PMID- 9614771
TI  - A five year study comparing early retirements on medical grounds in ambulance
      personnel with those in other groups of health service staff. Part II: Causes of
      retirements.
AB  - The objective of this study was to compare morbidity between ambulance staff and
      other groups of health service workers, to facilitate planning of occupational
      health (OH) services. A retrospective study of employees of the Eastern Health
      and Social Services Board, Northern Ireland was conducted. Subject were 181 men
      and 353 women assessed at OH between 1988-92 and found eligible (on the basis of
      permanent incapacity) to apply for early retirement on medical grounds (EROMG).
      When causes of retirement were looked at it was found that musculoskeletal,
      circulatory and mental disorders were most common in all groups (overall making
      up three-quarters of retirements). Differences in causes of retirements between
      different groups of workers were not found to be statistically significant, but
      when male staff were compared ambulance staff showed the highest proportion of
      retirements due to circulatory disorders. Retirements due to musculoskeletal
      disorders occurred after shorter service than those due to mental disorders and
      those due to mental disorders occurred after shorter service than those due to
      circulatory disorders; these findings achieved statistical significance. In
      comparison with previous studies this study showed the highest proportion of
      ambulance retirements due to mental disorders, with an unexpectedly high
      proportion being related to alcohol problems. Occupational health services for
      ambulance staff would be best targeted towards facilitating the development of
      physical fitness and rehabilitation programmes, and health promotional activities
      such as training in stress management.

PMID- 9614772
TI  - Upper limb disorder due to manual pipetting.
AB  - This case report describes the occurrence of non-specific upper limb symptoms, in
      a 47-year-old female scientific officer, associated, with manual pipetting. The
      discussion considers the difficulty of risk assessment and reduction for this
      common procedure.

PMID- 9614774
TI  - Research methodology in occupational medicine.

PMID- 9614773
TI  - Nasal septal ulceration and perforation in jiggers.
AB  - The paper describes two cases of occupational ill-health in individuals working
      as jiggers in the chromium electroplating industry. Much has been written about
      the effects of chromic acid on the platers who may work directly over the plating
      baths, but a literature search failed to identify any reports of ill-health in
      those who work alongside platers preparing the items to be placed into the baths.
      One case of nasal ulceration and one of nasal septal perforation are described.
      Reference is made to the role of the 'responsible person' in health surveillance
      for such workers to allow early identification of occupationally acquired ill
      health and prevention of further cases.

PMID- 9614776
TI  - Intraoperative non-puncture laparoscopic examination of contralateral internal
      inguinal rings is feasible in children with unilateral hydrocele.
AB  - BACKGROUND: Intraoperative non-puncture laparoscopic examination using the hernia
      sac as the scope entrance has been successfully conducted in children with
      unilateral inguinal hernia. This technique selects patients for contralateral
      inguinal exploration. In spite of the thin and narrow processus vaginalis,
      children with unilateral hydrocele encounter the same problem of subsequent
      contralateral inguinal hernia or hydrocele. In this study, we discuss the
      feasibility of this technique in children with unilateral hydrocele. METHODS:
      From July 1993 to September 1995, 91 children with unilateral hydrocele were
      examined during surgery at our institution. The results, including success rate,
      complications, patent rate of contralateral internal ring and contralateral
      subsequent hernia or hydrocele, at at least one year follow-up, were compared
      with those of 329 children with unilateral hernia undergoing the same examination
      during this period. RESULTS: A patent contralateral processus vaginalis was
      recognized in 31 children and all were confirmed by surgical exploration. The
      examination failed in three patients, of whom two had a tear in the processus
      vaginalis and one had retroperitoneal air dissection as a result of false
      insertion of the laparoscopic sheath. One patient had a postoperative wound
      infection. No patient with contralateral obliterated processus vaginalis
      developed inguinal hernia or hydrocele during follow-up of at least one year. The
      results were similar to those of the 329 children with hernia who underwent the
      same procedure in the same period. CONCLUSIONS: Intraoperative non-puncture
      laparoscopic examination is feasible in children with unilateral hydrocele.

PMID- 9614775
TI  - An electrophysiologic and pathologic study of peripheral nerves in individuals
      with Machado-Joseph disease.
AB  - BACKGROUND: Machado-Joseph disease (MJD) is characterized by cerebellar ataxia,
      pyramidal signs, progressive external ophthalmoplegia, and variable degrees of
      bulging eyes and dystonia. Electrophysiologic and histologic alterations of the
      peripheral nervous system in patients with MJD have rarely been reported.
      METHODS: The peripheral nerves of four patients with MJD who were identified by
      polymerase chain reaction were subjected to electrophysiologic testing and
      histologic study. Correlation analyses were made between clinical parameters and
      the electrophysiologic as well as histologic changes. RESULTS: Electrophysiologic
      studies demonstrated a marked reduction of sensory action potential, as well as a
      decrease in the compound motor action potential. Light microscopy of the sural
      nerves revealed marked loss of myelinated fibers, and morphometry studies showed
      a loss of large myelinated fibers. The severity of these pathologic changes was
      not related to the duration of the disease. CONCLUSIONS: In MJD, the peripheral
      nervous system was frequently affected. These findings were similar to those seen
      in Friedreich's ataxia, suggesting a loss of sensory and motor fibers probably
      following a lesion of the dorsal root ganglion and the anterior horns in the
      spinal cord.

PMID- 9614777
TI  - Status of trace elements in patients with idiopathic dilated cardiomyopathy in
      central Taiwan.
AB  - BACKGROUND: Sporadic cases of dilated cardiomyopathy (DCM) are often seen in
      central Taiwan. Though trace elements may play a role in the pathogenesis of
      idiopathic DCM, there are no reports concerning study of Taiwan's population in
      relation to trace elements in patients with DCM. METHODS: Serum selenium, zinc,
      copper and iron concentrations and blood glutathione peroxidase (GPX) activity
      were measured in 32 patients with DCM (24 males, 8 females; mean age, 44 +/- 14
      years) and 31 age-matched normal volunteers (16 males, 15 females; mean age, 38
      +/- 12 years). RESULTS: The average serum selenium concentration of 27.6 +/- 8.4
      micrograms/l found in the DCM group was significantly lower than the average
      concentration of 47.2 +/- 14.7 micrograms/l in the normal group. Blood GPX
      activity was also significantly lower in the DCM group than in the normal group.
      Serum selenium concentration correlated well with blood GPX activity in the
      studied subjects. Serum copper and iron concentrations were significantly higher
      in the DCM group than in the normal group. There was no difference in serum zinc
      concentration between the two groups. CONCLUSIONS: Deficiency of serum selenium
      in association with a low blood GPX activity, and high serum copper and iron
      concentrations, are found in patients with idiopathic DCM in central Taiwan.

PMID- 9614778
TI  - Dopamine and dobutamine have different effects on heart rate variability in
      patients with congestive heart failure.
AB  - BACKGROUND: Autonomic dysfunction plays an important role in the pathogenesis,
      treatment and prognosis of congestive heart failure (CHF). Sympathomimetic amines
      have been widely used in the treatment of CHF, but reports on their autonomic
      effects in CHF are rare. This study was designed to evaluate the effects of
      dopamine and dobutamine on cardiac autonomic function as assessed by heart rate
      variability (HRV). METHODS: Twenty patients with symptomatic CHF (systolic
      dysfunction) were enrolled. After recording one-hour baseline electrocardiographs
      (ECGs), patients were randomly selected for either dopamine (4
      micrograms/kg/minute, Group A) or dobutamine (4 micrograms/kg/minute, Group B)
      treatment for three days. On the third day, a 24-hour ambulatory ECG was recorded
      and a tilt-table test was performed. Only furosemide and nitrates were allowed
      for adjunctive therapy. HRV was measured before and after treatment in both time
      and frequency domains. Frequency-domain HRV was also measured during head-up
      tilt. RESULTS: After treatment, all patients improved [New York Heart Association
      fraction (NYHA Fc) 3.7 to 2.0]. Group A patients had higher post-treatment 24
      hour HRV than those in Group B. SDNN (standard deviation of the average normal RR
      intervals in the entire ECG recording), SDANN (standard deviation of the average
      normal RR intervals for all five minute segments of an entire ECG recording) and
      SDNN indices in Group A were significantly higher than in Group B (90 +/- 33 ms
      vs 41 +/- 12 ms, 78 +/- 32 ms vs 36 +/- 11 ms, and 37 +/- 19 ms vs 16 +/- 7 ms,
      respectively, all p < 0.05). rMSSD (the square root of the mean of the squared
      differences between adjacent normal RR intervals over the entire ECG recording)
      and pNN50 (percentage of differences between adjacent normal RR intervals that
      are greater than 50 ms computed over the entire ECG recording) were also higher
      in Group A patients, with borderline significance. All measurements of total
      frequency and low-frequency and high-frequency components tended to be higher in
      Group A than Group B, but this was only significant for total frequency amplitude
      (22.9 +/- 13.4 ms vs 10.9 +/- 6.1 ms, p < 0.05). Dopamine but not dobutamine
      treatment seems to restore the depressed circadian change in frequency-domain HRV
      classically seen in patients with CHF. The HRV change during head-up tilting did
      not differ between the two groups. Three patients in Group B showed non-sustained
      ventricular tachycardia on ambulatory ECG during the treatment period.
      CONCLUSIONS: Dopamine and dobutamine have comparable therapeutic effects in
      patients with CHF, but low-dose dopamine more favorably affects cardiac autonomic
      function.

PMID- 9614779
TI  - Computed tomography in the determination of surgical emergency for symptomatic
      abdominal aortic aneurysm.
AB  - BACKGROUND: What is the best surgical timing for symptomatic AAA? Surely, the
      answer depends on accurate and prompt diagnosis of 'rupture or not'. Abdominal CT
      is one of the reliable and familiar diagnostic tools. We will present our own CT
      classification method for symptomatic AAA which is used as the guideline for
      'emergency or not'. METHODS: From January 1989 to January 1995, 52 patients with
      symptomatic AAA received diagnostic CT scan for quick disease differentiation and
      determination of surgical emergency. The findings were classified into four
      categories. Category I included 26 patients with intact aorta; Category II
      included four patients with contained retroperitoneal abdominal aortic leakage;
      Category III included 14 patients with contained massive retroperitoneal
      hematoma; and Category IV included eight patients with retroperitoneal or
      intraperitoneal active bleeding. RESULTS: Compared with the standard diagnosis of
      rupture via laparotomy, CT is an excellent tool, showing 88% sensitivity and 88%
      specificity. This is better than sonography, which has a high false-positive rate
      of 33% and low specificity of 62%. Hospital mortality was distinctive with 4.3%
      in Category I, none in Category II, 25% in Category III and 87.5% in Category IV.
      CONCLUSIONS: In our experience, CT scan is a better diagnostic tool than
      sonography for symptomatic AAA. Even the delay imposed by obtaining a
      preoperative CT scan in patients with possible ruptured aneurysm does not
      adversely affect the patient's outcome. The information obtained significantly
      aids not only preoperative but also intraoperative management.

PMID- 9614780
TI  - A SPECT study of patients with gait apraxia without evidence of frontal lobe
      dysfunction.
AB  - BACKGROUND: The pathogenesis of gait apraxia (GA) is unknown. Even though imaging
      studies provide excellent assessment of brain morphology, there is still a lack
      of congruous results. Single photon emission computed tomography (SPECT) using Tc
      99m hexamethylpropyleneamine oxime (HMPAO) may show alterations in regional
      cerebral blood flow (rCBF) and provide indirect information about brain
      metabolism. METHODS: We conducted a SPECT study of GA patients and evaluated the
      related cortical function. rCBF was assessed in 16 GA patients (15 male, one
      female; age range 65-79 years, mean 70.5 years) by SPECT using HMPAO. Mean HMPAO
      cortical or basal ganglia/cerebellum activity ratios were calculated. The regions
      of interest included the frontal lobe, parietal lobe and basal ganglia. A battery
      of GA tests and magnetic resonance imaging (MRI) of the brain were also performed
      in these 16 patients. RESULTS: Nine of the patients had equilibrium disorder, and
      all 16 patients had locomotion disorder. The MRI findings were lacunar infarct
      (16/16 in basal ganglia, or 6/16 in thalamus), leukoaraiosis (4/16), enlarged
      ventricle (3/16), frontal lesion (3/16) and parietal lesion (1/16). Lower rCBF
      was noted in the frontal lobe (3/16), occipital lobe (1/16, thalamus (7/16) and
      basal ganglia (9/16). Though SPECT showed decreased rCBF in nine patients (9/16),
      mean cortical and basal ganglia regional uptake ratios in the patient group were
      not significantly different from values in the control group (cortical p =
      0.0613; basal ganglia p = 0.0576, by Student's t-test). CONCLUSIONS: Though only
      a small number of patients were studied, it was clear that brain SPECT and MRI
      did not show any significant abnormalities in the frontal or parietal lobes of
      patients with GA. Thus, the pathogenesis of GA and its related anatomic lesion
      should be further investigated.

PMID- 9614781
TI  - Ocular metastases from breast carcinoma: a report of two cases.
AB  - Breast carcinoma metastases to the eye occur more frequently than is clinically
      recognized. The prevalence of this lesion is not appreciated because of the
      dominant clinical picture of metastases occurring in other organs or because a
      number of eye lesions are small and asymptomatic. With the increasing length of
      survival, more breast cancer patients will require care for ocular metastases. A
      thorough ophthalmic evaluation, aided by computed tomography or magnetic
      resonance imaging, usually confirms the diagnosis. Rapid progression of a lesion
      demands emergency therapy since the dysfunction produced by progressive disease
      may not otherwise be corrected. Early diagnosis of ocular metastases in patients
      with breast cancer is important because timely treatment may improve vision and
      quality of life in the time remaining to patients. Experience with two cases of
      metastases to the eye from breast cancer are presented, with a review of the
      literature.

PMID- 9614782
TI  - Elimination of hypercapnia may postpone the clinical presentation of malignant
      hyperthermia: a case report.
AB  - Malignant hyperthermia is a rare complication in clinical anesthesia, especially
      associated with the administration of succinylcholine or inhalation anesthetics.
      A 19-year-old patient, suffering from traumatic mandible fracture, underwent open
      reduction under general anesthesia. Unfortunately, following administration of
      succinylcholine, he also suffered severe facial twitch and the first episode of
      hypercapnia. After adequate management, the symptoms subsided. However, two hours
      later, the hypercapnia recurred, combined with progressive elevation of body
      temperature. After administration of intravenous dantrolene 120 mg, the patient's
      condition became stable and the procedure was completed without sequelae. As the
      muscle contracture test is not available in Taiwan, the clinical grading scale is
      presented as an alternative diagnostic method for malignant hyperthermia.

PMID- 9614783
TI  - Congenital megacystis: a case report.
AB  - Congenital megacystis without other anomalies is extremely rare. A female
      newborn, delivered by cesarean section at the gestational age of 36 weeks, was
      seen. Her prenatal sonogram at 28 weeks' gestation had demonstrated a large
      cystic lesion in the abdomen. Abdominal distention with a palpable mass,
      difficult feeding and vomiting were noted after delivery. Abdominal computed
      tomography scan revealed a large cyst in the middle abdomen without any other
      anomaly. Exploratory laparotomy was performed on the fourth day of life, and
      showed a large bladder with normal trigon and normal ureteral insertion. There
      was no abnormality of other abdominal organs. Reductive cystoplasty was performed
      and the post-operative course was uneventful. The infant was doing well after an
      eight-month follow-up. Although congenital megacystis is rare, it should be
      considered in the differential diagnosis of any intraabdominal cystic lesion
      demonstrated in a prenatal sonogram. The etiology is obscure, and the benefit of
      reductive cystoplasty needs more cases to be confirmed.

PMID- 9614784
TI  - Benign cystic teratoma of unilateral fallopian tube associated with intrauterine
      pregnancy: a case report.
AB  - Primary teratomas of the fallopian tube are extremely uncommon. To date, only
      about 50 cases have been reported in the literature. Six of them are reported to
      have been in conjunction with tubal ectopic pregnancies. Herein we present the
      first case of benign cystic teratoma of the unilateral fallopian tube associated
      with an intrauterine term pregnancy, reported in Taiwan.

PMID- 9614785
TI  - Seeking a port in a storm. The University of California Commission on the Future
      of Medical Education.

PMID- 9614786
TI  - California's county hospitals and the University of California graduate medical
      education system. Current issues and future directions.
AB  - California's county hospitals train 45% of the state's graduate medical
      residents, including 33% of residents in the University of California system.
      This paper describes the interrelationships of California's county hospitals and
      the University of California (UC) graduate medical education (GME) programs,
      highlighting key challenges facing both systems. The mission of California's
      county health care systems is to serve all who need health care services
      regardless of ability to pay. Locating UC GME programs in county hospitals helps
      serve the public missions of both institutions. Such partnerships enhance the GME
      experience of UC residents, provide key primary care training opportunities, and
      ensure continued health care access for indigent and uninsured populations. Only
      through affiliation with university training programs have county hospitals been
      able to run the cost-effective, quality programs that constitute an acceptable
      safety net for the poor. Financial stress, however, has led county hospitals and
      UC's GME programs to advocate for reform in both GME financing and indigent care
      funding. County hospitals must participate in constructing strategies for GME
      reform to assure that GME funding mechanisms provide for equitable compensation
      of county hospitals' essential role. Joint advocacy will also be essential in
      achieving significant indigent care policy reform.

PMID- 9614787
TI  - Strategies and methods for aligning current and best medical practices. The role
      of information technologies.
AB  - Rapid change in American medicine requires that physicians adjust established
      behaviors and acquire new skills. In this article, we address three questions:
      What do we know about how to change physicians' practices? How can physicians
      take advantage of new and evolving information technologies that are likely to
      have an impact on the future practice of medicine? and What strategic educational
      interventions will best enable physicians to show competencies in information
      management and readiness to change practice? We outline four guiding principles
      for incorporating information systems tools into both medical education and
      practice, and we make eight recommendations for the development of a new medical
      school curriculum. This curriculum will produce a future medical practitioner who
      is capable of using information technologies to systematically measure practice
      performance, appropriateness, and effectiveness while updating knowledge
      efficiently.

PMID- 9614789
TI  - The role of the physician in the emerging health care environment.
AB  - What do patients want from their physicians? This article reviews research on the
      role of the physician attained through surveys of the public and of physicians.
      The results from the two groups are surprisingly similar; communication is seen
      as an essential component of the physician's role. Further, we found that the
      public's ratings of the medical profession depend heavily on their experience
      with personal physicians. This paper reviews previous research on the importance
      of effective communication to patient satisfaction, adherence, and the outcomes
      of treatment, and it considers ways in which physician-patient communication is
      being affected by recent changes in the health care system. Suggestions for
      medical education and for the structure of primary and specialty patient care are
      offered.

PMID- 9614790
TI  - Continuing medical education: past, present, future.
AB  - Medical education can be divided into three segments: undergraduate, graduate,
      and continuing. Of these, continuing medical education (CME) clearly takes place
      for the longest time--if the practicing physician is to employ recent scientific
      developments that translate into optimal practice. Our assignment was to examine
      the past, present, and future of CME. We evaluated what forms it has taken and
      what forms it may take. We also include a review of the evidence of its impact.

PMID- 9614788
TI  - Emerging opportunities for educational partnerships between managed care
      organizations and academic health centers.
AB  - Medical schools, teaching hospitals, and managed care organizations have a vested
      interest in shaping the knowledge, skills, and attitudes of the next generation
      of physicians who must adapt to significant changes in the financing and delivery
      of health care. This article summarizes the rationale for educational
      partnerships between managed care and academic medicine based on a review of
      three decades of well-documented experimentation in the literature. Discussed are
      some of the most important characteristics of the successful partnerships being
      forged in the current healthcare environment based on new kinds of relationships
      between faculty and non-university clinician educators. What had been referred to
      in previous decades as the "teaching-HMO" is now being complemented by community
      based links between academic health centers and managed care plans. Several
      public and private sources have been generous in providing venture capital to
      support many of these innovations. However, their continued operation will depend
      on models for health care networks that can identify and manage the revenue and
      costs associated with the missions of education, clinical services, and research.

PMID- 9614791
TI  - Advances in information technology. Implications for medical education.
AB  - Few kinds of technology have had as broad an impact on the recent affairs of
      humanity as have information technologies. The appearance and rapid spread in the
      past several years of innovations such as the Internet's World Wide Web and the
      emergence of computer networks connecting tens to hundreds of millions of people
      worldwide have occurred with startling rapidity. These global events portend
      substantial changes in the delivery of health care, the conduct of biomedical
      research, and the undergraduate, graduate, and continuing education of health
      professionals. This report will attempt to succinctly review the following: (1)
      the characteristics of modern information technologies and recent trends that are
      most relevant to medical education and to the world in which future
      practitioners, researchers, and educators will live and work; (2) the
      implications of these technologies for the development of educational goals (in
      other words, the specific information technology skills that future health
      professionals will need); (3) the issues associated with the use of these
      technologies in the process of education; and (4) implications for near-term
      action by University of California medical schools and academic medical centers.

PMID- 9614793
TI  - The transformation of academic health in the United States.
AB  - Like all health care institutions, the nation's academic health centers are
      facing the need for fundamental change in structure and opportunity. This article
      examines the trends in five major areas: research, higher education,
      specialization, finance, and organization. The impact of these trends on the
      academic health centers is explored.

PMID- 9614792
TI  - The role of diversity in the health care needs of California.
AB  - Socioeconomic, racial, and ethic diversity influence many facets of health care,
      including access to health services, the morbidity and mortality of disease, and
      the process of training health care professionals. California has an increasingly
      diverse population, and it is essential that the University of California medical
      schools carefully address the role of diversity in medical education and in
      education for the many other professionals who have a key role in the provision
      of care and services to Californians. In this paper, we provide evidence in
      support of the belief that the University of California system must train a
      physician workforce that reflects the racial, ethnic, and socioeconomic
      characteristics of California's population in order to provide equitable health
      care to all segments of the state's people.

PMID- 9614794
TI  - Economists' perspectives on health care delivery in California as of 1995.
AB  - The health care delivery system is made up of providers--hospitals and doctors-
      increasingly organized into medical groups. Medical groups interact with payors,
      primarily health maintenance organizations, that increasingly pass through both
      risk and prices from increasingly demanding purchasers. This article summarizes
      the present and future prospects for each of these groups.

PMID- 9614795
TI  - Adapting residency training. Training adaptable residents.
AB  - Graduate medical education has been criticized for failing to adequately prepare
      young physicians to enter the workforce upon completion of their training. In
      addressing this criticism, the author makes arguments both for and against this
      assertion. Broad qualitative changes (graduate medical education training
      position allocation, subspecialists' role in health care delivery, educational
      quality, faculty development, and faculty promotion) that graduate medical
      education has undergone and is undergoing are discussed. Population health
      management, clinical resource management, teamwork, continuous quality
      improvement, ethics, and evidence-based medicine are addressed as important
      curricular elements for residency training. Innovations in graduate medical
      education that are being introduced as well as those that should be tried are
      discussed. Finally, the author asserts that although residency education should
      not be vocationally driven by the needs of managed care organizations, a powerful
      opportunity exists for collaborative educational research between academic
      medicine and managed care organizations. In a health care environment undergoing
      rapid changes, the primary goals of graduate medical education have not
      significantly changed: to produce compassionate physicians with a passion for
      lifelong learning who have leadership skills, are critical thinkers, skilled at
      self-assessment, and able to adapt to the needs of the health care marketplace.

PMID- 9614796
TI  - Disease and injury in California with projections to the year 2007. Implications
      for medical education.
AB  - In this article, as part of an evaluation of the future of medical education in
      California, we characterize the distribution of disease and injury in California;
      identify major factors that affect the epidemiology of disease and injury in
      California, and project the burden of disease and injury for California's
      population to the year 2007. Our goal is to elucidate the major causes of illness
      and disability at present and in the near future in order to focus state
      resources on the interventions likely to have the greatest impact. Data from
      various governmental agencies were utilized; the base year, 1993, is the most
      recent year with sufficient information available when this report was prepared.
      Several major risk factors have decreased, including smoking (30% decline from
      1984 to 1993) and drinking and driving. However, hypertension prevalence has not
      changed, and overweight has increased dramatically. Poverty continues to burden
      about 15% of Californians, with poverty highest among children. During 1993,
      220,271 Californians died, with 3 major causes accounting for 61% of these
      deaths: coronary heart disease (31%), cancer (23%), and stroke (7%). In terms of
      potential years of life lost (years lost before age 65), the most important
      causes of death in 1993 were unintentional injury (756 years lost/100,000
      population), cancer (632 years), and the acquired immunodeficiency syndrome
      (AIDS; 491 years). Mortality rates were highest among blacks and lowest among
      Asians. Overall mortality in California has been declining for decades; in just 1
      decade, from 1980 to 1991, mortality declined from 780 to 680 deaths per 100,000
      population. Several major causes of death have declined, including coronary heart
      disease, stroke, unintentional injury, cirrhosis, and suicide, while others have
      increased, for example, chronic obstructive lung disease and diabetes mellitus.
      Death from AIDS increased dramatically in the past decade, but is leveling off,
      and death from cancer is beginning to decline. Rates for overall mortality and
      morbidity, and for most specific conditions, should continue to decline. A
      projected 28% population increase by 2007 will yield a corresponding increase in
      the absolute level of disease cases and death; a disproportionate increase in
      younger and older groups will yield increased conditions affecting young
      (unintentional injury, AIDS) and older (heart disease, cancer, stroke, diabetes
      mellitus) people. Californians should experience overall improved health in
      coming years, reaping benefits of reduced environmental and behavioral risk
      factors as well as improved medical treatment and rehabilitation. Coordinated
      strategies for health promotion, disease prevention, delivery of medical
      treatment, and rehabilitation are needed to maintain and improve present levels
      of health across the life span.

PMID- 9614797
TI  - Recent and emerging trends in undergraduate medical education. Curricular
      responses to a rapidly changing health care system.

PMID- 9614798
TI  - Physician supply and medical education in California. A comparison with national
      trends.
AB  - Concerns have been voiced about an impending oversupply of physicians in the
      United States. Do these concerns also apply to California, a state with many
      unique demographic characteristics? We examined trends in physician supply and
      medical education in California and the United States between 1980 and 1995 to
      better inform the formulation of workforce policies appropriate to the state's
      requirements for physicians. We found that similar to the United States,
      California has more than an ample supply of physicians in the aggregate, but too
      many specialists, too few underrepresented racial/ethnic minority physicians, and
      poor distribution of physicians across the state. However, recent growth in the
      supply of practicing physicians and resident physicians per capita in California
      has been much less dramatic than in the country overall. The state's unusually
      high rate of population growth has enabled California, unlike the United States
      as a whole, to absorb large increases in the number of practicing physicians and
      residents during 1980 to 1995 without substantially increasing the physician-to
      population ratio. Due to a projected slowing of the state's rate of population
      growth, the supply of physicians per capita in the state will begin to rise
      steeply in coming years unless the state implements prompt reductions in the
      production of specialists. An immediate 25% reduction in specialist residency
      positions would be necessary to bring the state's supply of practicing
      specialists in line with projected physician requirements for the state by 2020.
      We conclude that major changes will be required if the state's residency programs
      and medical schools are to produce the number and mix of physicians the state
      requires. California's medical schools and residency programs will need to act in
      concert with federal and state government to develop effective policies to
      address the imbalance between physician supply and state requirements.

PMID- 9614799
TI  - Changing nature of physician licensure. Implications for medical education in
      California.
AB  - Recent upheavals within health care delivery, technological advances, and
      changing attitudes among consumers have challenged and changed health professions
      licensure. At the same time, traditional regulatory frameworks remain in place.
      Beginning with a comparison of California's physician regulation with other
      states, we explore this tension between established regulatory systems and
      emerging reforms. Current trends in regulatory reform across the United States
      and in California include efforts to standardize practice requirements, expand
      scopes of practice for nonphysicians, and restructure boards. Because of these
      trends, medical educators will be expected to prepare physicians to practice
      under increased scrutiny and expectations of accountability; promote
      interdisciplinary education, training, and practice; and step up the efforts
      toward uniformity in medical education, training, and practice.

PMID- 9614800
TI  - Overview of graduate medical education. Funding streams, policy problems, and
      options for reform.
AB  - In this article, we examine the financing mechanisms for graduate medical
      education (GME) in the United States. In so doing, we identify Medicare as the
      single largest contributor to GME and the most important barrier to producing a
      physician workforce that is appropriately sized, balanced, and skilled. Until
      passage of the 1997 Budget Reconciliation Agreement, the structure of Medicare
      payments promoted overproduction and skewed production toward training
      specialists in tertiary settings. We then examine the various reform proposals
      put forward by major health care organizations and policy bodies. These
      organizations generally agree on seven policy objectives: Remove incentives that
      promote expanded resident production; Base the GME subsidy on actual costs and
      distribute it more uniformly; Focus reductions on specialty residency positions;
      Provide GME payments for training provided in ambulatory, community, and managed
      care sites; Decouple Medicare GME reimbursement from payments to health
      maintenance organizations for patient care; Require all health insurers to
      contribute to GME; and Ensure that reductions in the GME subsidy do not reduce
      access to care for low-income persons. A myriad of different mechanisms for
      achieving these objectives have been recommended, many of which could be melded
      together to form a comprehensive approach to GME reform. The prospects for
      meaningful GME reform are dim in the absence of broader Medicare reform. The
      costs to stake-holders are too concentrated while the benefits to the public are
      too diffuse for GME reform to stand alone. But the political imperative to deal
      with the federal budget's short-term deficit and Medicare's long-term solvency
      will likely create an opportunity for GME reform. An addendum has been added that
      shows how the 1997 Budget Reconciliation Agreement addresses most of the major
      reform objectives identified but that several important issues remain unresolved.

PMID- 9614801
TI  - Nurse practitioners, certified nurse midwives, and physician assistants in
      California.
AB  - California's health care industry includes workers prepared in many ways to
      perform many jobs. One significant group of health care workers prepared to
      provide care that often overlaps with physician-generated services is known as
      "nonphysician providers." Commonly, this label refers to nurse practitioners
      (NPs), certified nurse midwives (CNMs), and physician assistants (PAs). In this
      article, we will describe this group in five main areas: (1) the characteristics
      of the current and projected workforce and programs preparing these
      professionals; (2) the current skill expectations and knowledge bases of each;
      (3) trends in the education of these health professionals; (4) innovative models
      of education of these health professionals; and (5) the inclusion of NPs, PAs,
      and CNMs in workforce planning in a changing health care system. We conclude
      that, particularly in light of the overlapping functions of this provider group
      with many physician functions, the NP, CNM, and NP workforces must be recognized
      and considered when planning for the future of the physician workforce.

PMID- 9614802
TI  - University of California Commission on the Future of Medical Education. July
      1997. Final report.

PMID- 9614803
TI  - European Society of Anaesthesiologists annual congress. Barcelone, Spain, 25-28
      April 1998. Abstracts.

PMID- 9614804
TI  - Adjuvant Therapy of Primary Breast Cancer, 6th International Conference. Olma
      Messen St. Gallen. February 25-28, 1998. Abstracts.

PMID- 9614805
TI  - The British Society of Gastroenterology annual meeting. Harrogate, 10-13 March
      1998. Abstracts.

PMID- 9614806
TI  - British Cardiac Society annual meeting. Glasgow, 19-21 May 1998. Abstracts.

PMID- 9614807
TI  - International Association In Dental Research, Argentine division, XXX annual
      meeting. La Cumbre, Cordoba, Argentina. October 23-25, 1997. Abstracts.

PMID- 9614808
TI  - Reflex sympathetic dystrophy. Outcome and measurement studies. Introduction.

PMID- 9614809
TI  - Variation in measurements of grip strength. A study in reflex sympathetic
      dystrophy patients.
AB  - The clinical picture of reflex sympathetic dystrophy (RSD) is characterized by a
      combination of the triad: autonomic, motor and sensory changes. In this study,
      the grip strength is measured in 29 upper extremity RSD patients. We used the
      generalizability theory to assess the extent of the disagreement or differences
      (errors in measurement) within or between observers and interactions between
      observer-session and repetition of the measurements. The aims of our study were
      to determine the different sources of variation in grip strength tests and the
      smallest detectable differences (SDD) as well as the reliability of upper
      extremity grip strength tests in RSD patients. The main sources of variation of
      measurement errors were observer, patient/observer interactions and
      patient/session/observer interaction and a random source. We found that the
      generalizability theory is useful for estimating the sources of measurement
      error. Clinical examinations for muscle strength measurements, as a part of a
      total clinical examination, for example for a disability payment or worker's
      compensation in case of RSD patients should be done by more than one observer in
      more than one session and more than once.

PMID- 9614810
TI  - Reflex sympathetic dystrophy of the upper extremity--a 5.5-year follow-up. Part
      I. Impairments and perceived disability.
AB  - The aim of this retrospective and long-term follow-up study was to identify
      impairments resulting from reflex sympathetic dystrophy (RSD) of the upper
      extremity and to analyze the relationship between impairment and disability in
      RSD patients. The study group consisted of a referred sample of 65 RSD patients,
      with clinical signs in the upper extremity. RSD developed after fractures of the
      wrist or hand in 29 patients or after a carpal tunnel release in 9 patients. The
      mean interval between the RSD diagnosis and our evaluation was 5.5 (3-9) years
      (SD = 0.8). The main outcome measurements were the impairments assessed by
      standard physical examination. ADL and pain were quantified with a visual
      analogue scale (VAS). Pain was evaluated immediately before and after the
      physical examination and the perceived pain was determined in the week before the
      examination. Significant differences in impairments were found between the
      affected and the unaffected sides (p < 0.05). According to the AMA-guides, the
      impairments did not lead to disabilities. Significant correlations were found
      between VAS-ADL and VAS-pain in the last week prior to evaluation and full fist
      grip-strength. Pain seems to be the most disabling effect.

PMID- 9614811
TI  - Reflex sympathetic dystrophy of the upper extremity--a 5.5-year follow-up. Part
      II. Social life events, general health and changes in occupation.
AB  - The aim of this retrospective long-term follow-up study was to describe the
      psychosocial aspects, such as social life events (SLE), around the causative
      event of reflex sympathetic dystrophy (RSD) and the psychological history of 65
      patients, 3-9 years after RSD of the upper extremity. General health and long
      term changes in occupation were assessed by means of a general health
      questionnaire (RAND-36) and a structured interview, respectively. SLE, with a
      life-change unit rate more than 35, was present in 32 patients. A psychological
      (or psychiatric) history was found in 22 patients. In total, 60% of the patients
      had a SLE and/or a psychological history. The pain scores of the RAND-36 among
      RSD patients differed significantly from those of the control group. 17 patients
      changed occupation after RSD. Nearly 30% of the patients had to stop work for
      more than one year. The results show a high coincidence between RSD and
      associated psychosocial disorders and this may play a role in intensifying and
      prolonging the symptomatology of RSD.

PMID- 9614812
TI  - Internet access.

PMID- 9614813
TI  - The stigma facing drug abusers impedes treatment.

PMID- 9614814
TI  - The risk is in the transfusion, not the donation.

PMID- 9614815
TI  - Letting the public know.

PMID- 9614816
TI  - Rural medicine: real action needed.

PMID- 9614817
TI  - Rural medicine: real action needed.

PMID- 9614818
TI  - Complementary medicine in the hospital.

PMID- 9614819
TI  - Increase in Alzheimer's disease: artifact or real?

PMID- 9614820
TI  - How many physicians does Canada need to care for our aging population?
AB  - BACKGROUND: There is concern that the aging of Canada's population will strain
      our health care system. The authors address this concern by examining changes in
      the physician supply between 1986 and 1994 and by assessing the availability of
      physicians in 1994 relative to population growth and aging, and relative to
      supply levels in the benchmark province of Alberta. METHODS: Physician numbers
      were obtained from the Canadian Institute for Health Information. The amount of
      services provided by each specialty to each patient age group was analysed using
      Manitoba physician claims data. Population growth statistics were obtained from
      Statistics Canada. Age- and specialty-specific utilization data and age-specific
      population growth patterns were used to estimate the number and type of
      physicians that would have been required in each province to keep up with
      population growth between 1986 and 1994, in comparison with actual changes in the
      physician numbers. Physician supply in Alberta was used as a benchmark against
      which other provinces were measured. RESULTS: Overall, Canada's physician supply
      between 1986 and 1994 kept pace with population growth and aging. Some
      specialties grew much faster than population changes warranted, whereas others
      grew more slowly. By province, the supply of general practitioners (GPs) grew
      much faster than the population served in New Brunswick (16.6%), Alberta (6.5%)
      and Quebec (5.3%); the GP supply lagged behind in Prince Edward Island (-5.4%).
      Specialist supply outpaced population growth substantially in Nova Scotia
      (10.4%), Newfoundland (8.5%), New Brunswick (7.3%) and Saskatchewan (6.8%); it
      lagged behind in British Columbia (-9.2%). Using Alberta as the benchmark
      resulted in a different assessment: Newfoundland (15.5%) and BC (11.7%) had large
      surpluses of GPs by 1994, whereas PEI (-21.1%), New Brunswick (-14.8%) and
      Manitoba (-11.1%) had substantial deficits; Quebec (37.3%), Ontario (24.0%), Nova
      Scotia (11.6%), Manitoba (8.2%) and BC (7.6%) had large surpluses of specialists
      by 1994, whereas PEI (-28.6%), New Brunswick (-25.9%) and Newfoundland (-23.8%)
      had large deficits. INTERPRETATION: The aging of Canada's population poses no
      threat of shortage to the Canadian physician supply in general, nor to most
      specialist groups. The marked deviations in provincial physician supply from that
      of the benchmark province challenge us to understand the costs and benefits of
      variations in physician resources across Canada and to achieve a more equitable
      needs-based availability of physicians within provinces and across the country.

PMID- 9614821
TI  - The need for acute, subacute and nonacute care at 105 general hospital sites in
      Ontario. Joint Policy and Planning Committee Non-Acute Hospitalization Project
      Working Group.
AB  - BACKGROUND: Previous studies of hospital utilization have not taken into account
      the use of acute care beds for subacute care. The authors determined the
      proportion of patients who required acute, subacute and nonacute care on
      admission and during their hospital stay in general hospitals in Ontario. From
      this analysis, they identified areas where the efficiency of care delivery might
      be improved. METHODS: Ninety-eight of 189 acute care hospitals in Ontario, at 105
      sites, participated in a review that used explicit criteria for rating acuity
      developed by Inter-Qual Inc., Marlborough, Mass. The records of 13,242 patients
      who were discharged over a 9-month period in 1995 after hospital care for 1 of 8
      high-volume, high-variability diagnoses or procedures were randomly selected for
      review. Patients were categorized on the basis of the level of care (acute,
      subacute or nonacute) they required on admission and during subsequent days of
      hospital care. RESULTS: Of all admissions, 62.2% were acute, 19.7% subacute and
      18.1% nonacute. The patients most likely to require acute care on admission were
      those with acute myocardial infarction (96.2% of 1826 patients) or
      cerebrovascular accident (84.0% of 1596 patients) and those admitted for elective
      surgery on the day of their procedure (73.4% of 3993 patients). However, 41.1% of
      patients awaiting hip or knee replacement were admitted the day before surgery so
      did not require acute care on admission. The proportion of patients who required
      acute care on admission and during the subsequent hospital stay declined with
      age; the proportion of patients needing nonacute care did not vary with age.
      After admission, acute care was needed on 27.5% of subsequent days, subacute care
      on 40.2% and nonacute care on 32.3%. The need for acute care on admission was a
      predictor of need for acute care during subsequent hospital stay among patients
      with medical conditions. The proportion of patients requiring subacute care
      during the subsequent hospital stay increased with age, decreased with the number
      of inpatient beds in each hospital and was highest among patients with congestive
      heart failure, chronic obstructive pulmonary disease and pneumonia.
      INTERPRETATION: In 1995, inpatients requiring subacute care accounted for a
      substantial proportion of nonacute care days in Ontario's general hospitals.
      These findings suggest a need to evaluate the efficiencies that might be achieved
      by introducing a subacute category of care into the Canadian health care system.
      Generally, efforts are needed to reduce the proportion of admissions for nonacute
      care and of in-hospital days for other than acute care.

PMID- 9614822
TI  - Child abuse: a community problem.

PMID- 9614823
TI  - Ethics in clinical research: searching for absolutes.

PMID- 9614825
TI  - Improving the accuracy of death certification.
AB  - BACKGROUND: Population-based mortality statistics are derived from the
      information recorded on death certificates. This information is used for many
      important purposes, such as the development of public health programs and the
      allocation of health care resources. Although most physicians are confronted with
      the task of completing death certificates, many do not receive adequate training
      in this skill. Resulting inaccuracies in information undermine the quality of the
      data derived from death certificates. METHODS: An educational intervention was
      designed and implemented to improve internal medicine residents' accuracy in
      death certificate completion. A total of 229 death certificates (146 completed
      before and 83 completed after the intervention) were audited for major and minor
      errors, and the rates of errors before and after the intervention were compared.
      RESULTS: Major errors were identified on 32.9% of the death certificates
      completed before the intervention, a rate comparable to previously reported rates
      for internal medicine services in teaching hospitals. Following the intervention
      the major error rate decreased to 15.7% (p = 0.01). The reduction in the major
      error rate was accounted for by significant reductions in the rate of listing of
      mechanism of death without a legitimate underlying cause of death (15.8% v. 4.8%)
      (p = 0.01) and the rate of improper sequencing of death certificate information
      (15.8% v. 6.0%) (p = 0.03). INTERPRETATION: Errors are common in the completion
      of death certificates in the inpatient teaching hospital setting. The accuracy of
      death certification can be improved with the implementation of a simple
      educational intervention.

PMID- 9614824
TI  - Bioethics for clinicians: 14. Ethics and genetics in medicine.
AB  - Information about a patient's inherited risk of disease has important ethical and
      legal implications in clinical practice. Because genetic information is by nature
      highly personal yet familial, issues of confidentiality arise. Counselling and
      informed consent before testing are important in view of the social and
      psychological risks that accompany testing, the complexity of information
      surrounding testing, and the fact that effective interventions are often not
      available. Follow-up counselling is also important to help patients integrate
      test results into their lives and the lives of their relatives. Genetic
      counselling should be provided by practitioners who have up-to-date knowledge of
      the genetics of and the tests available for specific diseases, are aware of the
      social and psychological risks associated with testing, and are able to provide
      appropriate clinical follow-up. Some physicians may elect to refer patients for
      genetic counselling and testing. However, it is inevitable that all physicians
      will be involved in long-term follow-up both by monitoring for disease and by
      supporting the integration of genetic information into patients' lives.

PMID- 9614826
TI  - Unconventional therapies for cancer: 4. Hydrazine sulfate. Task Force on
      Alternative Therapies of the Canadian Breast Cancer Research Initiative.

PMID- 9614827
TI  - The disease that "bites the heart and licks the joints".

PMID- 9614828
TI  - Protect-your-prostate message delivered on Parliament Hill.
AB  - In March Charlotte Gray attended a luncheon on Parliament Hill where a message on
      prostate cancer was served along with the meatballs. Thirty MPs attended the
      event, and organizer Ted White hopes the prevention message delivered by Dr.
      Martin Gleave will eventually trickle down to politicians in other levels of
      government.

PMID- 9614829
TI  - Canada produces its first MD specializing in telemedicine.
AB  - Originally Dr. Rod Elford had planned to pursue a career in sports medicine. An
      introduction to space medicine and the possibilities inherent in telemedicine
      changed all that, and last year he became the first Canadian physician to
      complete a clinical fellowship in this emerging field. Observers think he is
      likely to be the first of many.

PMID- 9614830
TI  - Infertility treatment: lack of consensus plagues an unregulated field.
AB  - Each year, in an attempt to stimulate journalism students' interest in medical
      writing, CMAJ sponsors the Amy Chouinard Memorial Essay Prize. The $750 award is
      in memory of Amy Chouinard, a longtime and valued contributor to CMAJ and the
      Canadian Journal of Surgery. Students from any recognized journalism program at a
      Canadian college or university are eligible to enter, and the deadline for 1998
      entries is June 1. The 1997 winner, Megan Easton, presents a well-written and
      thorough account of the issues surrounding infertility treatment. Interest in the
      topic came naturally enough--her father, Dr. William Easton, is a urogynecologist
      in private practice in Scarborough, Ont.

PMID- 9614831
TI  - Fibre-optic links eliminate distances separating specialists, patients.
AB  - New types of telemedicine links are being tested in Ottawa and the definition
      they provide is so good that cardiologists can treat patients several hundred
      kilometres away. Dr. Wilbert Keon says this technology should not be seen as an
      expensive frill but as a needed advance that will make health care more
      efficient.

PMID- 9614832
TI  - Fallout from the plague years: multiple loss and its impact on gay men.

PMID- 9614833
TI  - Delay in presentation and start of treatment in leprosy patients: a case-control
      study of disabled and non-disabled patients in three different settings in
      Ethiopia.
AB  - The delay incurred by leprosy patients between the onset of symptoms and the
      start of treatment has not been well characterized. Because reducing this delay
      is likely to be the most productive of all activities aimed at preventing
      disability, we compared the various components of delay in disabled and
      nondisabled new leprosy cases in a case-control study. Disabled patients had a
      median overall delay of 26 months, while nondisabled patients incurred a delay of
      only 12 months. The total delay was divided into three components: a) the delay
      between the onset of symptoms and the first act of health-seeking behavior, which
      was significantly longer for disabled patients; b) the delay between the first
      action and the first visit to a recognized clinic, which was also significantly
      longer for disabled patients; and c) the delay between the first clinic visit and
      the start of treatment, which was important in some cases: in those patients
      whose delay was due to problems within the health services, disabled patients
      again had a significantly longer delay. The study also compared two rural areas
      of Ethiopia, one with high and one with low rates of disability in new cases.
      High rates of disability (and greater delay in starting treatment) were thus
      associated with high levels of stigma, being from the Christian rather than the
      Muslim community, and the use of traditional medicine. There was, surprisingly,
      no association with knowledge about the transmission, symptoms and curability of
      leprosy. Implications for health promotion activities are discussed.

PMID- 9614834
TI  - Leprosy reactions--complications of steroid therapy.
AB  - The adverse effects of corticosteroid therapy while treating 830 patients
      suffering from leprosy reaction (type 1 = 581; type 2 = 249) are presented. Some
      of the adverse effects were cosmetically distressing, while others were
      disabling. Patients suffering from type 2 reaction--because of the tendency of
      the reaction to recur over a long time--needed steroids for a longer duration;
      hence, adverse effects were more frequent. Measures to counter some of the
      adverse effects are suggested and the need to identify drugs with potentially
      less adverse effects is emphasized.

PMID- 9614835
TI  - DNA amplification for detection of leprosy and assessment of efficacy of leprosy
      chemotherapy.
AB  - Polymerase chain reaction (PCR) for the detection of Mycobacterium leprae was
      applied to fresh skin biopsies and slit-skin smears from 122 untreated leprosy
      patients. The PCR positivity rates in biopsies were 95.6% in multibacillary (MB)
      cases and 44.2% in paucibacillary (PB) cases. Following 1 month of treatment, MB
      cases declined by 54.3% and PB cases by 61.8% of initial values. Six-month values
      also declined from initial positivity rates to 50.3% and 53.8% of initial values
      in MB and PB, respectively. Larger declines in the rate of positivity were seen
      for skin-smear samples at 1 and 6 months in both MB and PB, but overall PCR
      positivity rates were lower than biopsy rates for M. leprae.

PMID- 9614836
TI  - Fractionation, characterization and diagnostic potential of circulating leprosy
      antigens isolated from sera of lepromatous leprosy patients.
AB  - Circulating antigen was isolated from lepromatous sera by ammonium sulfate
      precipitation. The protein fraction between 36% and 75% ammonium sulfate was
      reactive with leprosy sera. Further fractionation of Ultrogel AcA 34 gel
      filtration column gave four protein fractions, CLA1, CLA2, CLA3 and CLA4. CLA1
      and CLA2 showed antigenic activity. On SDS-PAGE analysis and elution of the
      protein fractions, CLA1-7, CLA2-1 and CLA2-7 were found to be reactive with
      leprosy sera. On evaluating the diagnostic utility of these fractions, CLA1-7
      could detect IgG antibodies in 80% of the lepromatous (LL) and in 40% of the
      tuberculoid (TT) serum samples. Fraction CLA2-1 reacted with IgM antibodies in
      80% of the LL and TT patients; fraction CLA2-7 reacted with IgM antibodies in 70%
      of the LL and TT sera. Biochemical characterization indicated that CLA1-7 was a
      glycoprotein while CLA2-1 and CLA2-7 were lipoproteins in nature. When tested by
      an inhibition ELISA, fraction CLA2-7 inhibited the binding of anticeramide
      antibodies to a ceramide-coated plate while thin-layer chromatography of
      fractions CLA2-1 and CLA2-7 showed a spot with an Rf value similar to that of
      standard ceramide. This study thus shows for the first time the presence of
      ceramide in circulating leprosy antigen.

PMID- 9614837
TI  - Histopathological features of lepromatous iridocyclitis; a case report.
AB  - A peripheral iridectomy specimen which included a portion of the ciliary body
      from an advanced lepromatous leprosy patient was studied histopathologically. The
      lepromatous granuloma in the iris was similar in content and appearance to that
      of skin lesions. It appeared that even in this advanced lepromatous patient the
      dilator muscles of the iris were preserved. This study agrees with the earlier
      observation that the dysfunction of the iris in lepromatous disease is most
      probably the result of autonomic nerve destruction. Further, it is possible that
      the lepromatous involvement of the iris may reflect the histopathological changes
      in the ciliary body.

PMID- 9614838
TI  - Dietary habits, food intake and functional outcomes in those with a history of
      Hansen's disease in Korea.
AB  - This study shows that the nutrition and health status of ex-leprosy patients in
      Korea was marginal. Their nutrient intakes were low, especially from
      micronutrients which were associated with food from animal sources. Dietary
      quality was discriminated by food habits, such as skipping meals, irregularity of
      meals, food purchase and meal preparation. Dietary quality was best predicted by
      food habits followed by physical fitness and nutrition knowledge. Our subjects
      were nutrition-conscious, but they did not have accurate information. These
      findings suggest that our study population needs nutrition education.

PMID- 9614839
TI  - Leprosy research and patient care over the past century.

PMID- 9614840
TI  - A case of lymphocytic vasculitis with infiltration of dermal nerves resembling
      indeterminate leprosy.

PMID- 9614841
TI  - Survival of HIV-positive and HIV-negative leprosy patients in Mwanza, Tanzania.

PMID- 9614842
TI  - Relapse of multibacillary leprosy after rifampin and ofloxacin treatment for 28
      days; a case report.

PMID- 9614844
TI  - Chromoblastomycosis simulating lepromatous leprosy.

PMID- 9614843
TI  - Abnormal capillary proliferation in the iris of a leprosy patient.

PMID- 9614845
TI  - Comparison of pentoxifylline, thalidomide and prednisone in the treatment of ENL.

PMID- 9614846
TI  - Rare transcripts of interferon-gamma detected in lepromatous leprosy cases.

PMID- 9614847
TI  - Independent evaluation of leprosy elimination activities in Bangladesh, 11-23
      September 1997.

PMID- 9614848
TI  - 1997 Damien-Dutton Award.

PMID- 9614849
TI  - Differential effects of progesterone and its analogues on the contractility of
      the murine jejunum in vitro.
AB  - Epidemiological studies have demonstrated a higher prevalence of gastrointestinal
      motility disturbances in women compared with men. This may partly be due to the
      effects of sex hormones on smooth muscle cells. To further characterize the
      mechanisms by which sex hormones affect intestinal smooth muscle, we studied the
      effects of several structurally related progestins on intestinal contractility.
      Segments of the murine intestine oriented along the longitudinal axis were
      connected to force displacement transducers. We recorded the isometric tension
      generated by the murine jejunum spontaneously and after cholinergic stimulation.
      The baseline tension, amplitude of spontaneous contractions, and increase in
      tension after cholinergic stimulation were measured in the presence and absence
      of various steroid hormones. Progesterone dose dependently decreased the
      contractile activity of the murine jejunum. This effect occurred within less than
      1 min and could not be inhibited by a specific blocker of the progesterone
      receptor, suggesting a nongenomic pathway. Experiments with several progestins
      demonstrated a stereoselectivity of this steroid hormone effect. This was most
      pronounced for dihydroprogesterone: the 5 alpha form did not affect intestinal
      contractility, while the stereoisomer 5 beta-dihydroprogesterone significantly
      inhibited smooth muscle tension. We conclude that progesterone significantly
      inhibits the contractility of the murine jejunum in vitro. The differential
      effects of various structural analogues argue against a nonspecific effect of the
      steroid hormones on the lipid bilayer with secondary functional alterations of
      membrane proteins. Rather, they suggest a specific interaction between the
      steroid hormone and a still unidentified protein that differs in its function and
      pharmacological profile from the known progesterone receptor.

PMID- 9614850
TI  - Afterload sensitivity of nonlinear end-systolic pressure-volume relation vs
      preload recruitable stroke work in conscious dogs.
AB  - The observations in vivo of a non-linear, afterload-sensitive end-systolic
      pressure-volume relation (ESPVR) and a linear, load-insensitive preload
      recruitable stroke work (PRSW) relation may be reconciled by considering the PRSW
      as a product of both the ventricular ESPVR and the arterial elastance (Ea). We
      obtained pressure-volume data from eight conscious dogs. The ESPVR was nonlinear,
      and its trajectory was afterload-dependent. The PRSW was linear and load
      independent. Arterial elastance changed with both acute reductions in preload and
      steady-state changes in afterload. The PRSW relation thus describes both
      myocardial function and ventricular-arterial interaction and is a useful index of
      cardiovascular performance in patients.

PMID- 9614851
TI  - Protective effects of lazaroid U74389G on intestinal graft after heterotopic
      small bowel transplantation in rats.
AB  - BACKGROUND: Experimental studies have shown that 21-aminosteroids (21-A) are
      powerful inhibitors of superoxide-mediated iron-dependent lipid peroxidation.
      This study was aimed at determining how far the blocking effect of one of these
      substances (lazaroid U74389G) on lipid peroxidation protects intestinal grafts
      morphologically and biologically in a heterotopic transplant model (SBT) in rats.
      ANIMALS AND METHODS: Heterotopic LEW were performed using Ringer lactate (4
      degrees C) as preservation solution. In Group 1 (n = 7) the donor and recipient
      animals received 3 and 6 mg/kg of the 21-A U74389G, respectively. Group 2 (n = 7)
      received the same doses of the vehicle of the drug. Sham group underwent only a
      laparotomy. Bacterial translocation (BT) was determined in mesenteric lymph nodes
      (MLN), liver (L), and spleen (S) 60 min after reperfusion. Tissue myeloperoxidase
      (MPO), malondialdehyde (MDA), and percentage conversion xanthine
      dehydrogenase/xanthine oxidase (XD/XO) were also determined in the ileal graft.
      Histological damage was graded according to Park's classification. RESULTS:
      Tissue MDA (nmol/mg prot) was significantly lower in Group 1 (0.53 +/- 0.09) than
      in Group 2 (3.66 +/- 1, P < 0.05) and showed levels similar to those of the sham
      operated group (0.40 +/- 0.05). Injury grades were also significantly different
      in both study groups (Group 1, 0-1; Group 2, 2-3, P < 0.05). BT (log CFU/g
      tissue) in Group 1 were MLN, 0; L, 0.36; and S, 0. In Group 2, MLN, 1.07; L,
      0.81; and S, 1.49 (P < 0.05 in MLN). Increase in MPO activity (U/g prot) in
      comparison with sham-operated animals was similar in the two study groups (Group
      1, 1.49 +/- 0.58; Group 2, 1.22 +/- 0.46; Sham, 0.34 +/- 0.37 (P < 0.05 1,2 vs
      sham). Conversion of XD to XO was unaffected by the supplementation of the drug.
      CONCLUSION: 21A U74389G inhibits lipid peroxidation, protects intestinal graft,
      and reduces BT after heterotopic SBT in rats.

PMID- 9614852
TI  - Release of PDGF-BB and bFGF by human endothelial cells seeded on expanded
      polytetrafluoroethylene vascular grafts.
AB  - BACKGROUND: The majority of endothelial cell (EC) seeded graft failures are due
      to anastomotic neointimal fibrous hyperplasia. We investigated the PDGF-BB and
      bFGF release in vitro by umbilical vein EC seeded on precoated expanded
      polytetrafluoroethylene (ePTFE) prostheses. MATERIALS: EC harvested from human
      umbilical veins were seeded into ePTFE (30 microns internodal distance, 1 cm2 in
      diameter) disks. ePTFE disks uncoated or precoated with collagen type I,
      fibronectin, and Matrigel were used, and EC seeded into plastic wells coated as
      ePTFE disks or uncoated plastic wells served as controls. Scanning electron
      microscopy study assessed EC coverage. The presence of bFGF and PDGF-BB in serum
      free conditioned media from EC seeded into ePTFE grafts and EC seeded into wells
      was determined by the inhibition antibody-binding assay 72 h after seeding.
      RESULTS: EC coverage was similar in uncoated and coated ePTFE grafts. The release
      of PDGF-BB and bFGF by EC seeded into ePTFE grafts was significantly higher than
      that observed in EC seeded into plastic wells. The release of PDGF-BB and bFGF
      was independent from the various substrates used in the experiments in EC seeded
      into either ePTFE grafts or plastic wells. CONCLUSIONS: Our findings pointed out
      that in seeded ePTFE grafts, anastomotic smooth muscle cell proliferation and
      intimal thickening could take place underneath an intact endothelium because
      seeded EC may release several growth factors.

PMID- 9614853
TI  - Metallothionein-induced increase in mitochondrial inner membrane permeability.
AB  - OBJECTIVE: To elucidate the effect of metallothionein on the permeability of the
      mitochondrial inner membrane. BACKGROUND: Metallothionein (MT) is a 6-7-kDa
      protein which is rapidly produced by stressed cells. MT is induced by cytokines
      and other factors thought to mediate the stress response. The organelle with the
      highest concentration of MT is the mitochondrion. Therefore we studied the effect
      of MT on mitochondrial function. We chose to study the effect of MT on
      mitochondrial inner membrane permeability because of the role of this function in
      numerous cellular processes. METHODS: Mitochondria were isolated from livers of
      Sprague-Dawley rats by differential centrifugation and suspended in sucrose
      containing buffer. Changes in mitochondrial inner membrane permeability were
      monitored by following the change in absorbance at 540 nm. All experiments were
      of a paired design. RESULTS: We found that an increase in inner membrane
      permeability was induced by physiological metallothionein 1 (MT1) concentrations
      between 6 and 50 microM. There was no increase in the effect beyond 50 microM.
      The metals of MT1, zinc, and cadmium alone had no effect at physiological
      concentrations. The action of MT1 was inhibited by the aliphatic polyamine,
      spermine, as well as magnesium both at physiological concentrations. Spermine was
      effective whether added before or after MT1. Metallothionein 2 of different Zn2+
      and Cd2+ compositions induced different kinetics of pore opening. CONCLUSIONS:
      These experiments reveal the possibility that the permeability of the
      mitochondrial inner membrane is regulated by relative concentrations of MT,
      spermine, and magnesium. The metal composition of MT could also play a role in
      this regulation.

PMID- 9614854
TI  - Cytotoxic effects of basic FGF and heparin binding EGF conjugated with cytotoxin
      saporin on vascular cell cultures.
AB  - Vascular smooth muscle cell (SMC) proliferation is an integral component of
      intimal lesion formation. In this study we compared the mitogenic effects of
      basic fibroblast growth factor (bFGF) and heparin binding epidermal growth factor
      (HBEGF) and the cytotoxic effects of bFGF and HBEGF conjugated with plant
      cytotoxin saporin (SAP) on vascular cell cultures. Human vascular SMCs and
      endothelial cells were cultured and FGF receptor-1 (FGFR-1) and EGF receptor
      (EGFR) expression were detected by immunohistochemical staining. Cells were grown
      in 24-well plates. Variable amounts of testing drugs (bFGF, HBEGF, SAP, bFGF-SAP,
      or HBEGF-SAP) were added to quadruplicate wells after 24 h. Cells without drugs
      were used as control. The total number of cells was counted at 72 h using a
      hemocytometer. The cultured human vascular SMCs and endothelial cells expressed
      both FGFR-1 and EGFR with predominant perinuclear localization. bFGF and HBEGF
      demonstrated equally potent mitogenic effects on SMC proliferation. SAP alone
      showed a limited cytotoxic effect on both SMCs and endothelial cells. bFGF had a
      more potent effect on endothelial cell proliferation than HBEGF. bFGF-SAP was
      equally cytotoxic for both SMCs and endothelial cells, while HBEGF-SAP had a more
      selectively cytotoxic effect on SMCs than on endothelial cells. These data
      suggest that the mitogenic effects of bFGF and HBEGF and the cytotoxic effects of
      bFGF-SAP and HBEGF-SAP may both be mediated by their corresponding growth factor
      receptors. Because of its selective cytotoxic effect on SMCs, HBEGF-SAP may
      become a more attractive agent for controlling intimal lesion formation.

PMID- 9614855
TI  - Amrinone, a selective phosphodiesterase III inhibitor, improves microcirculation
      and flap survival: a comparative study with prostaglandin E1.
AB  - BACKGROUND: Amrinone, a selective phosphodiesterase (PDE) III inhibitor, is a
      newly developed agent that possesses a combination of positive inotropic and
      vasodilating properties as a result of preventing the degradation of cAMP and it
      has recently been licensed for treatment of heart failure alone. Amrinone is
      expected to be useful for the treatment not only of heart failure but also of
      peripheral circulatory disorders, including vascular disease, and for ischemic
      flaps, because it improves microcirculatory hemodynamics. To investigate
      potential therapeutic applications of amrinone, we evaluated its ability to
      improve microcirculatory hemodynamics and flap survival. MATERIALS AND METHODS:
      The rat skinfold chamber technique was employed to quantify microcirculation
      directly in vivo. The improved survival area of random flaps in rats treated with
      amrinone was examined to assess therapeutic efficacy of this drug. Its effects
      were compared with those of prostaglandin E1 (PGE1), which has been widely
      approved as an agent for improving hemodynamics. RESULTS: Microcirculatory blood
      flow and flap survival area were significantly increased in both amrinone- and
      PGE1-treated animals, compared to the saline-treated controls. The ameliorating
      effects of amrinone were comparable to those of PGE1. CONCLUSIONS: The results of
      this study suggest amrinone to be a potentially useful drug not only for treating
      heart failure but also for improving microcirculation in patients with vascular
      diseases and for postoperative care after reconstructive surgery.

PMID- 9614856
TI  - Enhanced cytolytic activity of tumor infiltrating lymphocytes (TILs) derived from
      an ICAM-1 transfected tumor in a murine model.
AB  - BACKGROUND: Tumors transfected with intercellular adhesion molecule-1 (ICAM-1), a
      known activator of resting T-cells, show an increased response to adoptive
      immunotherapy in vivo. This salutary effect may be due to increased sensitivity
      of the transfected tumor cells to cell-mediated cytotoxicity or an increased
      activity of the effector cells in the presence of increased amounts of ICAM-1.
      MATERIALS AND METHODS: MCA105 fibrosarcoma cells were transfected with the gene
      for ICAM-1, and a clone (Cl149) demonstrating significantly increased expression
      of ICAM-1 by fluorescent-activated cell sorter (FACS) and enzyme-linked
      immunosorbent assay (ELISA) compared to parental tumor was selected and cultured.
      Tumor infiltrating lymphocytes (TILs) were cultured in vitro from MCA105 and
      Cl149 tumors. K562 tumor cells were used as controls. RESULTS: TILs derived from
      MCA105 tumors lysed MCA105 (32% at 40:1) and Cl149 (52% at 40:1) target cells but
      not K562 (3%) demonstrating TIL specificity. TILs derived from Cl149 showed
      increased lysis of both target cells tested: MCA105 (62% at 40:1, P < 0.05) and
      Cl149 (98%) compared to lysis of the same target cells by MCA105 TILs as well as
      being specific (K562, 1%). CONCLUSIONS: These studies demonstrate that increased
      expression of ICAM-1 by a tumor cell results in increased lysis by TILs derived
      from either a tumor with enhanced ICAM-1 expression or a parental tumor, compared
      to the lysis of parental tumor target cells. In addition, TILs derived from a
      tumor with enhanced expression of ICAM-1 have significantly increased antitumor
      efficacy compared to TILs from the parental tumor, suggesting a possible
      mechanism for previously observed in vivo antitumor effects. These results
      suggest a new strategy for improving the efficacy of adoptive immunotherapy, by
      using lymphocytes derived from genetically altered tumors. The study of
      lymphocytes from genetically modified tumor cells may enable the elucidation of
      properties of various molecules believed important in cellular cytotoxicity.

PMID- 9614857
TI  - Distinct effects of allogeneic blood transfusion on splenocyte cytokine
      production after hemorrhagic shock.
AB  - Allogeneic blood transfusion is known to be immunosuppressive in the settings of
      cancer and transplantation, but the contribution of blood transfusion to
      immunomodulation after hemorrhage is unknown. Our purpose was to determine the
      influence of allogeneic blood transfusion upon cytokine profiles following
      hemorrhagic shock, using a model which approximates the clinical setting.
      METHODS: Male C3H/HeN mice were hemorrhaged via femoral arterial catheters to a
      mean arterial pressure (MAP) of 35 +/- 5 mm Hg, which was maintained for 1 h.
      Mice were resuscitated with autologous blood (auto BT) or allogeneic blood (allo
      BT) from Balb/c mice (both equivalent to volume of shed blood), and crystalloid
      (2X the volume of shed blood)-infused at 0.05 ml/min. Animals were sacrificed at
      1, 2, and 5 days postshock, and splenocytes were cultured for 24 h with anti-CD3
      antibody. Supernatants were assayed for IL-2, IL-6, IL-10, and gamma-IFN by
      ELISA. RESULTS: Regardless of transfusion status, hemorrhagic shock resulted in
      increased IL-6 and gamma-IFN by Day 2 postshock. Distinct cytokine alterations
      after allogeneic transfusion were as follows. IL-2: transient elevation of
      splenocyte IL-2 production in the shock + allo BT group (P < 0.005 vs. shock +
      auto BT) at Postshock Day 2. IL-6: suppression in IL-6 production in the shock +
      allo BT group by Postshock Day 5 (P < 0.05 vs. shock + auto BT). IL-10:
      persistently elevated IL-10 production following shock + allo BT (Day 1, P <
      0.001 vs. shock + auto BT; Day 5; P < 0.05 vs. shock + auto BT). gamma-IFN:
      elevation in gamma-IFN production by Day 5 in the shock + allo BT group (P <
      0.0005 vs. shock + auto BT). CONCLUSIONS: Allogeneic blood transfusion results in
      distinct alterations in splenocyte production of IL-2, IL-6, IL-10, and gamma-IFN
      after hemorrhagic shock. This model reflects the clinical usage of blood products
      and demonstrates some of the immune alterations after transfusion.

PMID- 9614858
TI  - Prevention of adriamycin-induced skin necrosis with various free radical
      scavengers.
AB  - Infiltration of antitumor agents into subcutaneous tissues may either result in a
      local area of self-resolving inflammation or progress to full-thickness loss of
      skin and underlying vital structures. Inadvertent extravasation of adriamycin can
      result in severe tissue necrosis. The mechanism of this tissue damage is believed
      to be release of oxygen free radicals into the tissue. After adriamycin
      extravasation, the treatment groups were made up according to drugs used, EGb
      761, pentoxifylline, alpha-tocopherol acetate, and alpha-tocopherol succinate in
      rats. To prevent the necrosis and to decrease the tissue malondialdehyde levels,
      the most effective agent was found to be EGb 761, and pentoxifylline was also
      effective (P < 0.001). No difference was found between topical lanoline and
      saline (P > 0.05). The maximum ulcer diameter was obtained in 2 weeks. The
      maximum tissue malondialdehyde levels were obtained in 24 h, and in comparison to
      the control group the treatment groups showed lower levels. Our aim is to show
      the role of free radicals in the formation of skin necrosis as a cause of
      adriamycin extravasation and to prevent or decrease the skin necrosis using
      various free radical scavengers.

PMID- 9614859
TI  - Differential display of genes in normal and hypoplastic fetal murine lungs.
AB  - To evaluate lung development at the level of gene expression, a comparison was
      made between normal and hypoplastic murine fetal lungs by using the mRNA
      differential display technique. We focused on altered gene expressions at
      gestational day (Gd) 19 in normal and hypoplastic murine lungs. Hypoplastic fetal
      lungs were created by gavaging pregnant mice at Gd8 with 25 mg of nitrofen (2,4
      dichlorophenyl-p-nitrophenyl ether) [1]. Normal as well as gavaged mice were
      euthanized by an overdose of halothane at Gd19, and fetuses were removed by
      laparotomy. Lungs were excised and total RNA was extracted from normal and
      hypoplastic fetal lungs. Differential display technique was carried out using the
      RNAimage kit (GenHunter Corp., TN). Each reverse transcription and polymerase
      chain reaction (RT-PCR) was performed using one specific anchor primer H-T11M
      (5'HindIII-T11A/C/G3') and one arbitrary primer. We have used a total of 3
      different anchor primers and 24 arbitrary primers for each sample. There were 20
      differentially expressed cDNA clones, either induced, inhibited, enhanced, or
      reduced in hypoplastic fetal lungs as compared to normal. Of these, one clone
      (NL2) with reduced expression in Gd19 hypoplastic lungs had 100% homology with
      mouse nucleosome assembly protein I gene. Another clone (NT5) with induced
      expression in hypoplastic lungs is an unknown gene. Further, analyses of Northern
      blots of lungs from various gestational ages showed that the expression of NT5
      was induced in hypoplastic lungs at Gd18, whereas in normal lungs it was first
      expressed at the neonatal stage and was increasingly expressed into adulthood.
      There is a single hybridized band, approximately 400 bp long for NT5 message.
      Dexamethasone induced expression of NT5 in normal Gd14 pseudoglandular lungs
      cultured for 7 days; however, different growth factors did not. Northern blot
      hybridization of multiple adult mice tissues showed NT5 expression in the lung,
      intestine, and spleen. The thyromimetic action of nitrofen and the interactive
      functional pathways of dexamethasone with T3 are known. Therefore, we suggest
      that the isolation and characterization of NT5 may provide valuable information
      on the regulation of lung development.

PMID- 9614860
TI  - Differential production of apoptosis-modulating proteins in patients with
      hypertrophic burn scar.
AB  - BACKGROUND: The biochemical and cellular pathways resulting in the production of
      proliferative scar in the thermally injured patient remain incompletely
      elucidated. A promising area of investigation is the phenomenon of programmed
      cell death and its modulation. The following study was designed to quantify
      differential levels of the bcl-2 protooncogene and the Fas cell surface receptor,
      two apoptosis-modulating proteins, in the peripheral blood mononuclear cell
      (PBMC) fractions of burn patients with hypertrophic scar versus those considered
      to have healed normally. The study also encompassed an immunohistochemical
      examination of fibroblasts in vitro, to identify differential levels of Fas, bcl
      2, and interleukin converting enzyme (ICE). METHODS: PBMC fractions were isolated
      from two matched burn patient cohorts of 10 patients each, the experimental group
      carrying the clinical and histopathologic diagnosis of hypertrophic burn scar.
      The supernatant from each mitogenically stimulated specimen was halved and
      subjected to the Fas/APO-1 enzyme-linked immunosorbent assay (ELISA) and the bcl
      2 ELISA. Results for each assay were compared between groups by unpaired t tests.
      Further biopsy specimens of isolated proliferative scar were used in vitro to
      analyze the role of these apoptosis-modulating proteins and ICE. This
      immunoperoxidase technique was analyzed qualitatively. RESULTS: The expression of
      the bcl-2 protein in the PBMC fractions of the burn patients with hypertrophic
      scar is significantly elevated in comparison to the control cohort (307.72 +/-
      72.29 u/ml vs 31.55 +/- 6.73 u/ml; P = 0.0042). The quantitative levels of the
      Fas receptor did not differ significantly between the groups, respectively
      (0.3988 +/- 0.179 u/ml vs 0.2899 +/- 0.066 u/ml; P = 0.5787). Immunoperoxidase
      staining of proliferative scar fibroblasts and those from surrounding skin
      revealed relatively decreased levels of membrane-bound Fas and ICE. bcl-2 was not
      detectable in these specimens. CONCLUSIONS: Differential expression of the bcl-2
      protooncogene and the Fas cell surface receptor in the PBMC fraction of patients
      with burn injuries may suggest a disequilibrium in a complex biochemical
      signaling mechanism mediating programmed cell death. The increased levels of bcl
      2 could be responsible for delayed fibroblast apoptosis, resulting in the
      disruption of normal healing and subsequent hypertrophic scarring. This is
      confirmed by an in vitro examination of wound fibroblasts versus those from
      surrounding uninjured skin. This immunoperoxidase technique reveals a localized
      relative decrease in Fas and ICE, two apoptosis-inducing proteins, at the level
      of the fibroblast in the proliferative scar specimen.

PMID- 9614861
TI  - Pancreatic blood flow and its role in the pathophysiology of pancreatitis.

PMID- 9614862
TI  - Various types of HIV mixed infections in Cameroon.
AB  - In order to assess the incidence of HIV mixed infection as well as to clarify the
      molecular epidemiology of HIV in central Africa, we investigated 43 HIVs obtained
      from 211 Cameroonian AC, ARC, and AIDS patients in 1994 and 1995. Part of the pol
      region and part of the env region were phylogenetically analyzed. The genotypes
      observed were varied: of 43 specimens, 28 (65%) were subtype A, 1 (2%) was
      subtype B, 2 (5%) were subtype D, 3 (7%) were subtype F, and 2 (5%) were group O.
      Of the remaining 7 specimens, 3 were mixed infections with HIV-1 subtypes A and
      C, HIV-1 subtypes C and F, and HIV-2 subtype A and HIV-1 subtype A; 1 was a mixed
      infection with HIV-1 subtypes A and D and the highly divergent group O (triple
      infection); another 3 appeared to consist of mosaic genomes (A/G, A/E, and B/A
      recombinant). These data show that various types of mixed infection, such as
      between different subtypes of HIV-1 group M, between HIV-1 and HIV-2, and even
      between HIV-1 groups O and M, were confirmed at a rather high frequency
      (approximately 10%). The mixed infection is particularly significant where there
      is a greater variety of HIV-1 subtypes circulating, since it results in new
      genetic diversity generated by intersubtype recombination.

PMID- 9614863
TI  - Bacteriophage P2 and P4 morphogenesis: structure and function of the connector.
AB  - The connector, the structure located between the bacteriophage capsid and tail,
      is interesting from several points of view. The connector is in many cases
      involved in the initiation of the capsid assembly process, functions as a gate
      for DNA transport in and out of the capsid, and is, as implied by the name, the
      structure connecting a tail to the capsid. Occupying a position on a 5-fold axis
      in the capsid and connected to a coaxial 6-fold tail, it mediates a symmetry
      mismatch between the two. To understand how the connector is capable of all these
      interactions its structure needs to be worked out. We have focused on the
      bacteriophage P2/P4 connector, and here we report an image reconstruction based
      on 2D crystalline layers of connector protein expressed from a plasmid in the
      absence of other phage proteins. The overall design of the connector complies
      well with that of other phage connectors, being a toroid structure having a
      conspicuous central channel. Our data suggests a 12-fold symmetry, i.e., 12
      protrusions emerge from the more compact central part of the structure. However,
      rotational analysis of single particles suggests that there are both 12- and 13
      mers present in the crude sample. The connectors used in this image
      reconstruction work differ from connectors in virions by having retained the
      amino-terminal 26 amino acids normally cleaved off during the morphogenetic
      process. We have used different late gene mutants to demonstrate that this
      processing occurs during DNA packaging, since only mutants in gene P, coding for
      the large terminase subunit, accumulate uncleaved connector protein. The
      suggestion that the cleavage might be intimately involved in the DNA packaging
      process is substantiated by the fact that the fragment cleaved off is highly
      basic and is homologous to known DNA binding sequences.

PMID- 9614864
TI  - Lamivudine therapy of WHV-infected woodchucks.
AB  - Hepatitis B viruses establish a chronic, productive, and noncytopathic infection
      of hepatocytes. Viral products are produced by transcription from multiple copies
      (5-50) of covalently closed circular (ccc) viral DNA. This cccDNA does not
      replicate, but can be replaced by DNA precursors that are synthesized in the
      cytoplasm. The present study was carried out to determine if long-term treatment
      with an inhibitor of viral DNA synthesis would lead to loss of virus products,
      including cccDNA, from the liver of woodchucks chronically infected with
      woodchuck hepatitis virus. Viral DNA synthesis was inhibited with the nucleoside
      analog, lamivudine (2'-deoxy-3'-thiacytidine). Lamivudine treatment produced a
      slow but progressive decline in viral titers in serum, to about 0.3% or less of
      the initial level. However, even after maintenance of drug therapy for 3-12
      months, > 95% of the hepatocytes in most animals were still infected. Significant
      declines in the percentage of infected hepatocytes and of intrahepatic cccDNA
      levels were observed in only three woodchucks, two in the group receiving
      lamivudine and one in the placebo control group. Moreover, virus titers
      eventually rose in woodchucks receiving lamivudine, suggesting that drug
      resistant viruses began to spread through the liver starting at least as early as
      9-12 months of treatment. Three types of mutation that may be associated with
      drug resistance were found at this time, in a region upstream of the YMDD motif
      in the active site of the viral reverse transcriptase. The YMDD motif itself
      remained unchanged. Not unexpectedly, the lamivudine therapy did not have a
      impact on development of liver cancer.

PMID- 9614866
TI  - Determinants of rotavirus host range restriction--a heterologous bovine NSP1 gene
      does not affect replication kinetics in the pig.
AB  - The genetic basis of rotavirus host range restriction (host species specificity)
      is unknown but the NSP1 (fifth) gene has been implicated in some studies. We
      studied the replication kinetics in vivo of a NSP1 gene monoreassortant, E11, to
      assess the influence of a heterologous NSP1 gene on the ability to replicate in
      pigs. The monoreassortant possessed 10 genes from the porcine parent rotavirus
      SW20/21, which replicated productively in pigs, and the NSP1 gene from the bovine
      rotavirus UK which produced an abortive infection in pigs. Groups of up to four
      pigs were inoculated orally with 10(5) to 10(6) TCID50 of the monoreassortant,
      the porcine parent rotavirus, or the bovine parent rotavirus or were sham
      inoculated. The monoreassortant replicated productively in pigs with replication
      kinetics almost identical to the porcine parent rotavirus. During a 9-day
      observation period after inoculation, the number of days with virus in the
      faeces, the onset and duration of virus excretion, and peak titres in faeces were
      similar for the monoreassortant and the parent porcine rotavirus. The genetic
      composition of the viruses excreted in the faeces was confirmed as that of the
      inocula by PAGE. Thus possession of a heterologous NSP1 gene from a bovine
      rotavirus which failed to replicate in pigs did not produce an abortive infection
      or affect the replication kinetics in vivo. The genetic basis of host range
      restriction between porcine and bovine rotaviruses remains to be established.

PMID- 9614865
TI  - Internal/structures containing transcriptase-related proteins in top component
      particles of mammalian orthoreovirus.
AB  - The structure of mammalian orthoreovirus top component particles, which are
      profoundly deficient in the content of double-stranded RNA genome, was determined
      at 30 A resolution by transmission cryoelectron microscopy and three-dimensional
      image reconstruction. Previously undetected, ordered densities, appearing
      primarily as pentameric flowers in the reconstruction, were seen to extend 65 A
      inwardly from the inner capsid at the icosahedral fivefold axes. Identically
      positioned but lower density elements were observed in two types of partially
      uncoated top component particles obtained by limited proteolysis. The levels of
      three inner-capsid proteins-lamda 1, lamda 3, and mu 2-were reduced in concert
      with the internal densities during proteolytic uncoating. Since lamda 3 contains
      the catalytic regions of the viral RNA polymerase and since both lamda 1 and mu 2
      appear to play roles in transcription or mRNA capping, the internal structures
      are concluded to be complexes of the viral transcriptase-related enzymes. The
      findings have implications for the mechanisms of transcription and mRNA capping
      by orthoreovirus particles.

PMID- 9614867
TI  - Transmission and propagation in cell culture of virus produced by cells
      transfected with an infectious molecular clone of bovine leukemia virus.
AB  - A full-length molecular clone of bovine leukemia virus (BLV) pBLV-IF with two
      copies of a long terminal repeat (LTR) was constructed from a previously
      isolated, covalently closed, circular DNA clone, pB6490, that has one copy of the
      LTR and the pX region split at an EcoRI site. This molecular clone directed the
      synthesis of viral proteins and the induction of syncytia in transiently
      transfected cells. In addition, virus particles were released into the culture
      medium. Serial passages of transient transfectants also resulted in propagation
      of BLV. After transfection of five cell lines with linearized pBLV-IF and a
      neomycin-resistance gene, BLV-producing transfectants were established in cell
      lines COS-1 and 23CLN that did not form syncytia upon expression of BLV. In HeLa
      and FLK cells, BLV produced by a stable COS-1 transfectant was transmitted by
      both cell-free and cell-to-cell infection. Thus, pBLV-IF encoded an infectious
      provirus that successfully induced primary and secondary infections. This study
      indicates that the infectious molecular clone and the virus-producing
      transfectants could be useful for further examination of the biological
      properties of BLV.

PMID- 9614868
TI  - Cytotoxic T cells and neutralizing antibodies induced in rhesus monkeys by virus
      like particle HIV vaccines in the absence of protection from SHIV infection.
AB  - HIV Pr55gag has in the absence of other viral components the capacity to self
      assemble in budding noninfectious virus-like particles (VLP). The immunological
      spectrum of the HIV-1IIIB gag-derived VLP was expanded either by stable anchoring
      of chimeric modified gp 120 on the surface of the VLP (type 1) or by replacing
      sequences of the Pr55gag precursor by the V3 loop and a linear portion of the CD4
      binding domain (type 2). This noninfectious antigen delivery system was evaluated
      for immunogenicity and efficacy in rhesus macaques without adjuvants.
      Intramuscular immunization with both types of VLP induced high titers of gag
      specific antibodies ranging from 1/8000 to 1/510,000 for type 1 VLP and from
      1/4000 to 1/16,000 for type 2 VLP. Only animals immunized with type 1 VLP
      developed substantial endpoint titers of env-specific antibodies (1/2000
      1/32,000) with a neutralizing capacity at serum dilutions of 1/32-1/128. Gag- and
      env-specific cytotoxic T lymphocyte (CTL) activity was induced by both types of
      VLP at similar levels. Four weeks after the last immunization animals were
      challenged intravenously with 20 MID50 of the cell free homologous envelope
      simian/HIV-1IIIB chimeric challenge stock Despite HIV-1-specific neutralizing and
      CTL responses, all vaccinated animals became infected.

PMID- 9614869
TI  - Mutations in viral movement protein alter systemic infection and identify an
      intercellular barrier to entry into the phloem long-distance transport system.
AB  - Viral systemic infection of a plant host involves two processes, cell-to-cell
      movement and long-distance transport. Molecular determinants associated with
      these two processes were probed by investigating the effects that alanine
      scanning mutations in the movement protein (MP) of red clover necrotic mosaic
      virus (RCNMV) had on viral infection in the plant hosts Nicotiana edwardsonii,
      Vigna unguiculata (cowpea), and the experimental plant Nicotiana benthamiana.
      Plants were inoculated with RCNMV expressing wild-type and mutant forms of the
      MP. Immunocytochemical studies at the light and electron microscope levels were
      performed on these plants, using a polyclonal antibody raised against the RCNMV
      capsid protein to identify the cells/tissues that RCNMV could infect. These
      experiments demonstrated that one cellular boundary at which the RCNMV MP
      functions to facilitate entry into the phloem long-distance transport system is
      located at the interfaces between the bundle sheath and phloem parenchyma cells
      and the companion cell-sieve element complex. Interestingly, in Nicotiana
      tabacum, a host that only allows a local infection, RCNMV cell-to-cell movement
      was found to be blocked at this same intercellular boundary. Four mutants that
      were able to systemically infect N. benthamiana were partially or completely
      defective for systemic infection of N. edwardsonii and cowpea, which indicated
      that these MP mutants exhibited host-specific defects. Thus, the roles of the
      RCNMV MP in cell-to-cell movement and in long-distance transport appear to be
      genetically distinct. These results are discussed in terms of the mechanism by
      which RCN MV enters the phloem to establish a systemic infection.

PMID- 9614870
TI  - Different HTLV-I neutralization patterns among sera of patients infected with
      cosmopolitan HTLV-I.
AB  - To determine if sequence variations observed in cosmopolitan HTLV-I interfered
      with viral recognition by neutralizing antibodies, we evaluated the
      neutralization potential of sera from persons infected by HTLV-I of this clade
      selected for amino acid changes in their eny glycoproteins. Each serum was used
      to neutralize three previously described HTLV-I isolates, 2060, 2072, and 1010,
      that possess amino acid env sequences differing at several positions, one of them
      being located in the immunodominant and neutralizable domain (aa 187-199). The
      results obtained in syncytia and/or reporter gene inhibition assays showed that
      the neutralization pattern of the sera clearly differed and could be classified
      in three categories. Five sera completely neutralized the three viruses with an
      equivalent titer, two sera gave a maximum inhibition, with higher ID50 on the
      2072 virus than on the 2060 or 1010 viruses, and three sera had a stronger
      neutralization potential toward the 1010 virus than toward the 2060 virus. One of
      these sera partially neutralized the virus produced by 2072 cells, whereas
      neutralizing antibodies in the other two recognized the neutralizable epitopes on
      the 1010 or 2072 viruses equally well. Identification of amino acid sequences
      involved in induction of neutralizing antibodies with different recognition
      capacities could help identify new neutralizable epitopes of HTLV-I envelope
      glycoproteins and to better define the component(s) of an effective vaccine.

PMID- 9614871
TI  - Expression and mutational analysis of the baculovirus very late factor 1 (vlf-1)
      gene.
AB  - We have examined the expression and function of a gene, vlf-1, of Autographa
      californica nuclear polyhedrosis virus that is known to encode a regulator of
      very late gene transcription. Western blot analysis revealed that vlf-1 is
      expressed during the late phase of infection, primarily from 15 to 24 h
      postinfection. VLF-1 localized in the cell nucleus and was also present in the
      nucleocapsids of virus particles. Mapping of vlf-1 mRNA by primer extension
      showed that transcription initiates at a TAAG motif 71 bp upstream of the vlf-1
      open reading frame. Disruption of this TAAG motif abolished the ability of vlf-1
      to stimulate transcription from the very late polyhedrin gene (polh) promoter in
      transient expression assays, suggesting that vlf-1 expression is controlled by
      the TAAG motif. Using a highly efficient system to construct recombinant viruses
      with modifications in vlf-1, we confirmed that the TAAG motif was essential.
      Furthermore, efforts to construct null mutants of vlf-1 failed, suggesting that
      vlf-1 is an essential gene for virus replication. Computer-assisted sequence
      homology searches place vlf-1 in the lambda phage integrase family (McLachlin and
      Miller, 1994). None of the strictly conserved residues of this family which are
      found in vlf-1 could be changed in the viral genome, implying that the putative
      integrase activity of VLF-1 is associated with the essential function of vlf-1.
      However, mutation of a crucial active-site tyrosine did not affect the ability of
      vlf-1 to transactivate the polh promoter in transient expression assays,
      indicating that the very late transcriptional activity of VLF-1 does not require
      the integrase activity.

PMID- 9614872
TI  - Release of viral glycoproteins during Ebola virus infection.
AB  - Maturation and release of the Ebola virus glycoprotein GP were studied in cells
      infected with either Ebola or recombinant vaccinia viruses. Significant amounts
      of GP were found in the culture medium in nonvirion forms. The major form
      represented the large subunit GP1 that was shed after release of its disulfide
      linkage to the smaller transmembrane subunit GP2. The minor form were intact
      GP1,2 complexes incorporated into virosomes. Vector-expressed GP formed spikes
      morphologically indistinguishable from spikes on virus particles, indicating that
      spike assembly is independent of other viral proteins. Analysis of a truncation
      mutant revealed an early and almost complete release of GP1,2 molecules, showing
      that membrane anchoring is mediated by the carboxy-terminal hydrophobic domain of
      GP2. We have also compared wild-type virus which requires transcriptional editing
      for synthesis of full-length GP with a variant that does not depend on editing.
      Both viruses released comparable amounts of GP1, but the variant expressed only
      minute amounts of the small, soluble GP which is the expression product of
      nonedited mRNA species of the GP gene. The abundant shedding of soluble GP1 may
      play an important role in the immunopathology of Ebola hemorrhagic fever in
      experimentally and naturally infected hosts.

PMID- 9614873
TI  - The adeno-associated virus Rep78 major regulatory protein binds the cellular TATA
      binding protein in vitro and in vivo.
AB  - Rep78 is the major regulatory protein of adenoassociated virus (AAV). Rep78 is
      able to transcriptionally regulate all three of AAV's promoters, as well as a
      variety of heterologous promoters. In an attempt to understand the mechanism of
      action by which Rep78 is able to regulate gene expression, we are investigating
      Rep78's possible protein-protein interaction with basal transcription factors.
      One such critical basal transcription factor is the human TATA binding protein,
      TBP. TBP is a core factor required for the assemblage of the transcription
      initiation complex, TFIID. In this report an in vitro interaction between Rep78
      and TBP was demonstrated in three different assay systems, including West(far)
      Western analysis, electrophoretic mobility shift assay-supershift, and
      coimmunoprecipitation. Furthermore, using the yeast GAL4 two-hybrid system, an in
      vivo interaction between Rep78 and TBP was also demonstrated. Further still, the
      amino half of Rep78 is shown to be needed for Rep78-TBP interaction. Mutations
      within this region of Rep78 are known to be defective for transcriptional
      regulatory ability, suggesting a biological role for this interaction. Thus,
      Rep78 may regulate transcription through binding and regulating TBP's numerous
      interactions. Furthermore, as Rep78 is known to bind at least one other
      transcription factor (Sp 1) and likely others, Rep78 may function as a TBP
      associated factor in an altered TFIID-like complex.

PMID- 9614874
TI  - Identification of transcripts and promoter regions of ovine adenovirus OAV287.
AB  - The ovine adenovirus isolated OAV287 represents a new group of adenoviruses that
      are distinct from the Mast- and Aviadenoviruses by several criteria, including
      genome arrangement. The OAV major late promoter and some late transcripts were
      previously mapped. To better define the probable coding sequences and to identify
      the approximate location of early promoters a partial transcription map of the
      genome was elucidated using a PCR-based approach. This was possible because the
      complete nucleotide sequence of the genome was known. The strategy permitted the
      identification of transcription start sites and RNA splice junctions and allowed
      the approximate location of promoters in the lefthand end, IVa2, E2, P32K, and E4
      regions to be deduced. The data showed that lefthand end and E4 regions are
      controlled by three and two temporally distinct promoters, respectively. The E2
      region is controlled by a single promoter, in contrast to Mastadenoviruses, where
      E2 expression is controlled by the E2A and E2B promoters. The p32kDa structural
      protein at the lefthand end and the IVa2 protein are also expressed from their
      own promoters. These data contribute to the first overview of transcription from
      a non-Mastadenovirus genome.

PMID- 9614875
TI  - Conversion of VP1 to VPg in cells infected by infectious pancreatic necrosis
      virus.
AB  - The RNA polymerase VP1 of IPNV (a bisegmented dsRNA containing virus) is present
      in the virion both as a free polypeptide and as a genome-linked protein (VPg).
      Virion VP1 primes viral RNA synthesis in vitro (P. Dobos, 1995, Virology 208, 19
      25), and here we present data which suggest that protein-primed RNA synthesis may
      also take place in infectious pancreatic necrosis virus (IPNV)-infected cells.
      Anti-VP1 serum immunoprecipitated several polypeptides larger than the 94-kDa VP1
      of IPNV from [35S]methionine-labeled infected cell lysates. During denaturing,
      SDS-polyacrylamide gel electrophoresis these polypeptides formed a characteristic
      "ladder" which was resistant to alkaline phosphatase but sensitive to RNases,
      indicating that it consisted of VP1 polypeptides with oligoribonucleotides of
      various lengths attached to them. Probing the ladder with 5' and 3' end-specific,
      as well as plus-, or minus-strand-specific oligonucleotides revealed that they
      represent VP1 linked to 5' terminal sequences of genome segment A- and B-specific
      plus strands. Pulse-chase experiments in combination with two-dimensional
      polyacrylamide gel electrophoresis revealed that labeled VP1 could be chased to
      replicative intermediate, to ssRNA, to dsRNA, and eventually to virion VPg-dsRNA
      and that VP1 could be released from all these structures by RNase treatment. We
      suggest that these results are most compatible with the model where a VP1-pN
      structure acts as a primer for viral RNA synthesis in vivo, a mechanism that has
      been shown to occur in vitro.

PMID- 9614876
TI  - Immunization with a recombinant envelope protein (rgp90) of EIAV produces a
      spectrum of vaccine efficacy ranging from lack of clinical disease to severe
      enhancement.
AB  - We have previously reported that immunization of ponies with a baculovirus
      expressed recombinant surface unit envelope protein (rgp90) for equine infectious
      anemia virus (EIAV) resulted in enhancement of disease symptoms and virus
      replication in 4 of 4 vaccine recipients subjected to a heterologous virus
      challenge (rpg90 I vaccine trial) (Wang et al., 1994). To extend these studies of
      EIAV vaccine enhancement, two additional and independent rgp90 vaccine trials
      (rgp90 II and rgp90 III) were performed. Combined, a total of 13 ponies were
      immunized with the rgp90 immunogen using our standard vaccination procedures and
      challenged with a heterologous strain of EIAV. In contrast to the uniform
      enhancement observed in the rgp90 I vaccine trial, the severity of clinical
      symptoms varied markedly among the rgp90 recipients: 5 ponies experienced
      enhanced disease symptoms, 5 ponies experienced moderate disease symptoms, and 3
      ponies remained asymptomatic. Of particular interest, in the 5 ponies with
      enhanced clinical symptoms was a severe thrombocytopenia (< or = 105,000
      platelets/microliter) evident coincident with the first febrile episode following
      virus challenge. Thrombocytopenia was either absent (7/10 ponies) or
      substantially delayed (3/10 ponies) in naive control ponies inoculated with the
      standard EIAVPV challenge. Measurements of virus replication in the challenged
      vaccine recipients indicated a correlation between the level of viral RNA in
      plasma and the severity of the disease. Interestingly, an association was not
      observed between serum antibody reactivity to the vaccine or native viral
      antigens and the frequency of enhancement. Thus, these observations demonstrate a
      previously unrecognized complexity of rgp90 vaccine efficacy that has important
      implications for AIDS vaccine development.

PMID- 9614877
TI  - The hepatitis B virus seroconversion to anti-HBe is frequently associated with
      HBV genotype changes and selection of preS2-defective particles in chronically
      infected children.
AB  - In order to investigate the generation and selection of hepatitis B virus mutants
      and the influence of interferon on their evolution, a longitudinal study
      including 22 patients was performed. The complete preS1/S2 open reading frame was
      analyzed by direct sequencing from serum samples obtained before and after
      seroconversion to anti-HBe in 11 children without alpha-interferon treatment.
      Furthermore, in 11 cases with therapy additional samples obtained during
      interferon therapy were investigated. The comparison of each patient's preS
      sequences analyzed before and during therapy did not show any nucleotide change,
      while in both groups numerous silent and missense mutations were found
      immediately after seroconversion. Surprisingly, in 7 cases the hepatitis B virus
      changed genotype from A to D (subtype adw to ayw) after seroconversion.
      Additional rearrangements were observed in 4 patients. In 3 cases the selection
      of preS2 start codon mutants was detected after seroconversion and in 1
      individual a 183-nucleotide deletion was found during and after HBeAg positivity.
      In conclusion, the emergence of preS rearrangements and numerous base exchanges
      provide evidence for a strong selection process focused against the preS region.
      Moreover, the appearance of genotype changes after anti-HBe seroconversion
      reveales a thus far unrecognized event during the natural course of HBV infection
      in childhood.

PMID- 9614878
TI  - Ultrastructural and temporal observations of the potyvirus cylindrical inclusions
      (Cls) show that the Cl protein acts transiently in aiding virus movement.
AB  - A systematic ultrastructural study across the edge of an advancing infection in
      pea seed-borne mosaic potyvirus-infected pea cotyledons showed the cylindrical
      inclusion (CI) protein to exist in transient functional states. Initially, the
      characteristic CI pinwheel inclusion bodies were positioned centrally over the
      plasmodesmal apertures (including those of plasmodesmata connected to the
      previously infected cell), in agreement with a proposed role in virus movement
      (Carrington et al., 1998, Plant J., 13, in press). The viral coat protein was
      associated with these structures and was seen within the modified plasmodesma,
      most notably in a continuous channel that passed along the axis of the pinwheel
      and through the plasmodesma. The CI protein was not detected within the
      plasmodesmal cavities. Later in the infection (i.e., behind the zone of active
      virus replication) the CI was no longer associated with cell walls, or with coat
      protein, and showed signs of structural degeneration. In contrast, the coat
      protein remained within plasmodesmal cavities. The role of the CI in assisting
      virus movement is not known but the presence of the CI was linked with an
      apparent transient reduction in callose in the vicinity of the plasmodesmata.

PMID- 9614879
TI  - [Late effects of ionizing radiations on normal tissues].

PMID- 9614880
TI  - [Scoring system of late effects of radiations on normal tissues: the SOMA-LENT
      scale].
AB  - Radiation tolerance of normal tissues remains the limiting factor for delivering
      tumoricidal dose. The late toxicity of normal tissues is the most critical
      element of an irradiation: somatic, functional and structural alterations occur
      during the actual treatment itself, but late effects manifest months to years
      after acute effects heal, and may progress with time. The optimal therapeutic
      ratio ultimately requires not only complete tumor clearance, but also minimal
      residual injury to surrounding vital normal tissues. The disparity between the
      intensity of acute and late effects and the inability to predict the eventual
      manifestations of late normal tissue injury has made radiation oncologists
      recognize the importance of careful patient follow-up. There is so far no uniform
      toxicity scoring system to compare several clinical studies in the absence of a
      "common toxicity language". This justifies the need to establish a precise
      evaluation system for the analysis of late effects of radiation on normal
      tissues. The SOMA/LENT scoring system results from an international
      collaboration. European Organization Treatment of Cancer (EORTC) and Radiation
      Therapy Oncology Group (RTOG) have created subcommittees with the aim of
      addressing the question of standardized toxic effects criteria. This effort
      appeared as a necessity to standardize and improve the data recording, to then
      describe and evaluate uniform toxicity at regular time intervals. The current
      proposed scale is not yet validated, and should be used cautiously.

PMID- 9614881
TI  - [Biological mechanisms of late effects of ionizing radiations].
AB  - The daily practice of radiation oncology is increasingly influenced by the late
      tolerance of normal tissues. The treatment decision must be based on detailed
      arguments and the physician's duty to extensively inform his patients is
      emphasised every day. The incidence and severity of radiation-induced sequelae
      and late complications can be reduced by decreasing the total dose to the normal
      tissues, and by decreasing the dose protraction, provided that the interval
      between fractions remains longer than 6 to 8 hours. This approach yields a
      selective protection of late responding normal tissues, since tumours are less
      sensitive to the effects of fractionation. Despite its own limitations, the
      linear- quadratic model is nowadays the standard method to compare the biological
      effects of different radiation treatments.

PMID- 9614882
TI  - [Late effects of ionizing radiations on central nervous system, spinal cord and
      peripheral nerves].
AB  - Despite the lack of characteristic features, demyelination is the dominant
      feature of radiation induced late effects observed in cerebral nervous system and
      spinal cord. Acute, subacute and chronic changes are described in terms of
      pathological, clinical and radiological observations. Brain necrosis in adults is
      rarely noted below 60 Gy in conventional fractionation, while imaging changes are
      observed with lower doses. The most widely observed dose limit for the spinal
      cord is 45 Gy, in the absence of dose modifying chemotherapy. Tumor progression
      may be hard to distinguish from radiochemotherapy effects. The potential
      protective role of hyperfractionation is not yet clearly established. Peripheral
      nerves late effects, although rare, are described.

PMID- 9614883
TI  - [Late effects of radiation on the eye and ocular adnexa].
AB  - Late ocular effects after irradiation of the eyes and ocular adnexa are reviewed.
      Ocular and orbital injuries occur more often after irradiation of central nervous
      system neoplasms or treatment of paranasal sinus malignancies. The complete loss
      of vision is the major complication which is multifactorial. This paper describes
      the radiation effects and grading of ocular adnexa, lens, retina, optic nerves
      and orbit. The tolerance doses and treatment are described.

PMID- 9614884
TI  - [Late effects of ionizing radiations on head and neck region tissues].
AB  - Numerous structures are included in the irradiated volume of patients presenting
      with head and neck cancer: skin, mucosa, bone, teeth, cartilage, muscles,
      salivary glands, etc. Curative intent treatment of such tumours requires
      aggressive approach which can lead to severe sequellae. These sequellae are in
      most cases dose-dependent and volume-dependent. However, an appropriate technique
      might decrease the severity of such sequellae. Details of these late changes are
      presented, including their pathophysiology, clinical syndromes, potential
      treatment, and prevention.

PMID- 9614885
TI  - [Late effects of radiotherapy on the neuroendocrine system].
AB  - When the hypothalamic-pituitary axis (HPA) is included in the treatment field in
      children and adults, a variety of neuroendocrine disturbances are more common
      than has been appreciated in the past. Clinical damage to the pituitary and
      thyroid glands usually occurs months to years after treatment, and is preceded by
      a long subclinical phase. Primary brain tumors represent the largest group of
      malignant solid tumors in children. The survival rates of 50% reported in the
      literature are achieved at the expense of late occurring effects. Radiation
      induced abnormalities are generally dose-dependent. Growth hormone deficiency and
      premature sexual development can occur at doses as low as 18 Gy in conventional
      fractionation, and is the most common neuroendocrine problem in children. In
      patients treated with > 40 Gy on the HPA, deficiency of gonadotropins, thyroid
      stimulating hormone, and adrenocorticotropin can be found. Following high-dose
      radiotherapy (> 50 Gy), hyperprolactinemia can be seen, especially among young
      women. Most neuroendocrine disturbances that develop as a result of HPA can be
      treated efficiently, provided that an early detection of these endocrine
      dysfunctions abnormalities is done.

PMID- 9614886
TI  - [Late effects of ionizing radiations on the thyroid gland].
AB  - The thyroid is the purest endocrine gland in the body and is likely to produce
      clinically significant abnormalities after external radiotherapy. Functional
      clinical modifications after direct irradiation exceeding 30 Gy are essentially
      related to hypothyroidism which may be clinically overt or subclinical with
      normal serum free thyroxine levels and high thyrotropin concentrations; the risk
      of hyperthyroidism, silent thyroiditis and Hashimoto's disease is also increased.
      Secondary hypothyroidism related to irradiation of the hypothalamus and the
      pituitary gland may arise with doses over 40-50 Gy following treatment for brain
      and nasopharyngeal tumors--Morphological glandular modifications induced by
      radiotherapy are responsible for the appearance of benign adenomas, more rarely
      cystic degenerations and specially well differentiated papillary or follicular
      carcinomas among children and adults. After irradiation during childhood for
      benign or malignant tumors, thyroid cancers are more frequent, higher for younger
      children, and the relative excess risk is increased from 15.6-to 53-fold; tumors
      can belatedly occur, more than 35 years after initial therapy. Thereby, in order
      to limit excess morbidity, it is evident that long term supervision with careful
      clinical and biological evaluations is necessary for patients who previously
      received neck, upper mediastinum and pituitary radiation therapy.

PMID- 9614887
TI  - [Late effects of radiations on the esophagus].
AB  - Radiation-induced late effects of oesophagus are observed after treatment for
      various cancers. Acute reactions, mainly oesophagitis, are well known and
      accurately described; late effects share, for most of these, a common
      consequence: alteration of the main oesophageal function, namely to conduct the
      food bolus; clinically they are impaired in terms of mobility and stenosis. More
      rarely, ulcerations and pseudodiverticulae can be observed. Chemotherapy further
      increases the risk of late effects, especially in case of concomitant chemo
      radiotherapy. All numbers and statistical data on oesophagus late effects should
      be regarded with caution due to recent changes in the therapeutic attitudes (more
      and more combined chemotherapy-radiotherapy) and some progress in given cancer
      locations. A common scale like the LENT-SOMA should enable the clinician to
      better know these late effects on oesophagus which is required to initiate
      effective prevention measures and adapted treatments.

PMID- 9614888
TI  - [Pulmonary and cardiac late effects of ionizing radiations alone or combined with
      chemotherapy].
AB  - High doses of ionizing radiation (> 40 Gy) cause severe lung fibrosis in
      approximately 5% of the cases. There is a twofold increase when chemotherapy is
      added to ionizing radiation. Lung fibrosis is due to the destruction of lung
      tissue by ionizing radiation but also to various cytokine effects (PDGF-beta, TGF
      beta). Only a minority of patients (approximately 10%) with abnormal X-rays will
      experience clinical symptoms. The most important radiobiological parameters which
      accounts for pulmonary tolerance is the fraction size. Irradiation of the heart
      begets multifarious late sequelae which are often left unrecognized. Chronic
      pericarditis affects approximately 5% of the patients when the irradiation dose
      exceeds 40 Gy. Coronary artery disease can be diagnosed in 5 to 10% of the
      patients. This late complication is more likely to occur if the patient was young
      at the time of the irradiation or if other risk factors are associated. Valvular
      defects can be found in 15 to 30% of the patients. However, the mortality rate is
      very low (0.5%). Finally, conduction defects can also be seen in approximately 5%
      of the patients. It is very likely that the radiation dose given to the heart
      should not exceed 30 Gy if late sequelae are to be avoided.

PMID- 9614889
TI  - [Late effects of mammary radiotherapy on skin and subcutaneous tissues].
AB  - Late damages to the skin and subcutaneous tissues are almost inescapable because
      of the high skin doses required in the irradiation of breast tumours. While the
      clinical and histological descriptions date back to the first decades of the
      therapeutic use of ionising radiation, the recent advances in cellular and
      molecular biology have significantly contributed to the increased understanding
      of late skin injury mechanisms. In particular, sub-cutaneous fibrosis appears to
      be the partly reversible results of a continuous and self-maintained local
      process, possibly sensitive to therapeutic intervention. A second very active
      research avenue is the development of biologic assays potentially able to predict
      the probability of increased normal tissue injury after irradiation in individual
      patients. Such a test would allow the adaptation of the treatment modalities to
      the radiobiological behaviour of normal tissues. To date, these expectations have
      not been met. The quality of the irradiation and its modalities (total dose,
      fractionation, inter fraction interval) remain the main ways to achieve an
      optimal functional and cosmetic outcome.

PMID- 9614890
TI  - [Late effects of radiations on the liver].
AB  - Until recently, the liver was classified as a radioresistant organ, although it
      is in fact highly radiosensitive. The realization that the whole liver could be
      treated safely only with low doses of radiation led to the conclusion that
      radiation therapy had an extremely limited role in the treatment of intrahepatic
      malignancies. A resurgence of interest has been observed with the advent of
      conformal radiotherapy and the introduction of bone marrow transplantation with
      total body irradiation. The radiation-induced liver disease, often called
      radiation hepatitis, is a syndrome characterized by the development of anicteric
      ascites, approximately 2 weeks to 4 months after hepatic irradiation. Immediate
      tolerance is generally surprisingly good, and the subacute radiation injury is
      followed by a complete asymptomatic healing, although the late lesions may be
      associated with signs of chronic radiation hepatitis. Radiation hepatitis must be
      distinguished from chemoradiation-induced-hepatitis occurring in patients
      undergoing bone marrow transplantation and total body irradiation. Both syndromes
      demonstrate the same pathological lesion: veno-occlusive disease. The main
      treatment for radiation hepatitis is diuretics, although soma advocate steroids
      for severe cases.

PMID- 9614891
TI  - [Late effects of radiations on the kidney].
AB  - Clinical radiation damage to the kidney are nowadays a rare event. Nevertheless,
      this organ is very sensitive to radiation and dose exceeding 15 Gy may induce
      severe and life threatening damage many years after the treatment. Prevention
      remains the best treatment through a precise localisation of the kidneys before
      any irradiation of the upper abdomen.

PMID- 9614892
TI  - [Late effects of radiations on the bladder].
AB  - Clinical effects of radiation on bladder are in relation with their effects on
      various tissus of this organ. The most important is the vessels. According to
      clinical models; it is possible to evaluate the different factors, especially the
      dose and the irradiated volume. The risk of complications rise with these two
      factors. Drugs used in bladder cancer don't seem to increase the risk of
      complications. The prevention of the late effects lies on the tissue protection
      and on the precise evaluation of the irradiated volume in view to reduce them.

PMID- 9614893
TI  - [Late intestinal complications of adjuvant radiotherapy of rectal cancers].
AB  - Pre or postoperative pelvic irradiation has demonstrated a definitive efficacy in
      reducing the local failure rate of rectal cancer treated with surgery alone.
      However it can induce late small bowel morbidity that could alter the therapeutic
      ratio. The clinical pictures of radiation enteritis include obstruction and
      diarrhea/malabsorption. Prognostic factors that increase the risk of late small
      bowel complications include extended fields out of the pelvis, irradiation dose,
      inappropriate irradiation technique, and increased small bowel irradiated
      volumes. The addition of chemotherapy increases acute but not late toxicity.
      Recommendations concerning the clinical practice are described. Radiotherapy may
      also alter the residual sphincter function and we recommend to assess correctly
      these complications.

PMID- 9614894
TI  - [Rectal complications of radiotherapy].
AB  - Late rectal morbidity has been observed in 2%-25% of patients treated with
      radiotherapy using curative doses for prostate, cervix and rectal cancers. The
      major encountered clinical pictures are rectal proctitis, rectal/anal strictures,
      rectal bleeding, ulcers and fistula. Some may alter the patient's lifestyle while
      other may induce death. Recommendations concerning the clinical practice are
      described. The treatment of these late rectal effects include nutritional
      recommendations, laser, formalin application, and surgery.

PMID- 9614895
TI  - [Late effects of ionizing radiations on the testis].
AB  - Most of the basic data regarding the effect of radiation on the testis are issued
      from animal studies. They demonstrate the extreme radiosensitivity on the germ
      cell lineage but little is known about the reversible or definitive aspects of
      these radiation induced effects. In man, the late non stochastic effects of
      radiation to the testicule are mainly related to persisting spermatogenesis
      disturbances or/and hormone related problems. Morphological, physiological,
      radiobiological specificities of the human testis along with numerous parameters
      depending on radiation conditions make it difficult to evaluate the late effects
      and radiation tolerance doses. Evaluation of such effects based on a common scale
      for therapeutic radiation schedules would improve the present understanding and
      possibly prevent the occurrence of these delayed effects, for the benefit of
      patients.

PMID- 9614896
TI  - [Late effects of ionizing radiations on the vulva, vagina and uterus].
AB  - Reporting and scoring complications after radiotherapy of gynaecological cancers
      is difficult because of the variety of treatment techniques involved. Use of an
      international classification is necessary to compare results obtained in series
      of patients treated in different institutions. An international group of experts
      designed in the early nineties the so-called French-Italian glossary. This
      classification of late effects is now completed with the new LENT SOMA scales.
      This paper contains details of these late changes, including their
      pathophysiology, clinical syndromes, potential treatment, and prevention.

PMID- 9614897
TI  - [Late effects of radiotherapy on the skeletal muscle].
AB  - There are few data regarding the adverse effects of radiotherapy on skeletal
      muscle. This tissue is considered to be radioresistant. Muscle toxicity of
      radiation is unfrequent and does not represent a limiting factor for dose
      escalation.

PMID- 9614898
TI  - [Late effects of ionizing radiations on the bone marrow].
AB  - Bone marrow is a tissue with a high mitotic activity, and consequently
      exquisitely radiosensitive. The clinical effects of bone marrow irradiation and
      its ability of regeneration are related to the volume irradiated. Management of
      hematopoietic side effects of radiation include surveillance, antibiotics, blood
      products transfusion, and more scarcely hematopoietic growth factors, bone marrow
      transplantation and peripheral blood stem cells reinfusion.

PMID- 9614899
TI  - [Late effects of radiations on mature and growing bone].
AB  - The physiopathology of radiation-induced bone damage is no completely elucidated.
      Ionizing radiation may induce an inhibition or an impairment of growing bone.
      This fact is of particular importance in children, and represents one of the most
      important dose-limiting factors in the radiotherapeutic management of children
      with malignant diseases. Scoliosis, epiphyseal slippage, avascular necrosis,
      abnormalities of craniofacial growth may be observed after radiation. Child's age
      at the time of treatment, location of irradiated bone and irradiation
      characteristics may influence the radiation-related observed effects. In adults,
      pathological analysis of mature bone after ionizing radiation exposure are rare,
      suggesting that it is difficult to draw a clear feature of the action of
      radiation on the bone. Osteoporosis, medullary fibrosis and cytotoxicity on bone
      cells lead to fracture or necrosis. Various factors can influence bone tolerance
      to radiation such as bone involvement by tumor cells or infection, which is
      frequent is mandibulary osteoradionecrosis. Technical improvements in radiation
      techniques have also decreased radio-induced bone complications: the volume,
      fractionation and total dose are essential to consider. The absence of a
      consistent radiation-induced late effects evaluation scale has hampered efforts
      to analyze the influence of various therapeutic maneuvers and the comparison of
      results from different reported series. The currently proposed evaluation scale
      may help harmonizing the classification of radiation-induced bone late effects.

PMID- 9614900
TI  - [Late effects of radiotherapy in children].
AB  - Although most pediatric tumors can be cured with lower doses of radiation than
      their adult counterparts, long-term radiation-induced complications and sequelae
      remain a major concern both in terms of frequency and intensity. Most of them
      have been extensively documented in the pre-chemotherapeutic era like those
      affecting bone, cartilage and soft tissue growth or CNS and endocrine glands.
      More recently the emphasis has been put on the apparent increasing incidence of
      reported second malignancies. This could have been favored by the chemo-radiation
      combinations used in most children but also has been made possible mainly by the
      extensive follow-up of the increasing cohort of cured children.

PMID- 9614901
TI  - [Late effects of intraoperative radiotherapy].
AB  - Several experimental studies on animals have yielded to the tolerance single
      doses for different critical organs. Anatomical alterations are located
      essentially in the intima of the arteries with oedema, histio-lymphoplasmocytoid
      infiltration in a first time leading to arterial obstructions and necrosis after
      the 6th week. These radiation injuries are related to the IORT dose, the target
      volume and the time interval between the IORT treatment and the apparition of the
      side-effects. Moreover, some radiation induced sarcomas have been observed in
      animals after the 5th year which suggest that the follow-up period after IORT
      must be prolonged enough to appreciate the exact complications rate of IORT. If
      we exclude the usual post-operative complications, the complications observed in
      human IORT treatments may be either early side effects on small bowel, esophagus
      or late effects: peripheral neuropathies, osseous complications, and
      microvascular obstructions. A more precise clinical description and an improved
      knowledge of the relationships with different treatment characteristics should
      allow us to prevent more efficiently the IORT complications.

PMID- 9614902
TI  - [Radiation-induced cancers: state of the art in 1997].
AB  - Scientists now have available a large amount of data dealing with radiation
      induced neoplasms. These data went back to anecdotal observations which were made
      in the very first years of utilization of X-rays and radioactive elements. In
      fact, it is essentially the strict follow-up of the Japanese populations
      irradiated by the Hiroshima and Nagasaki bombing which allowed a more precise
      evaluation of the carcinogenicity of ionizing radiations. Further refinements
      came from therapeutical irradiations: it is now possible to study large cohorts
      of patients given well-known doses in well-defined volumes and followed for more
      than 20 years. Last but not least, a significant increase in the incidence and
      mortality of thyroid cancer has been detected in children contaminated by iodine
      radioisotopes after the Tchernobyl accident. Recently, some data suggested the
      emergence of "clusters" of leukemias close to some nuclear facilities, but this
      question remains highly polemical, both in France and in the UK. Other questions
      are still waiting for a precise answer; of course, the extrapolation of our
      available data to very low doses delivered at very low dose rates, but also the
      carcinogenic risk at high doses. For these "high" doses (about 30 to 70 Gy), a
      competition between mutagenesis and cell killing was expected, so that these dose
      levels were expected to be less carcinogenic than lower (a few sieverts) doses.
      Actually, recent data suggest that the carcinogenic risk goes on increasing up to
      relatively important doses. In addition, carcinogenic factors, such as tabacco,
      anticancer chemotherapy and individual susceptibility, are found more and more to
      be closely intricated with ionizing radiation in the genesis of a given cancer.
      Even if a number of questions are still pending, the already available data allow
      specialists, both in medicine and radioprotection, to edict strict rules which
      can be reasonably expected to have significantly reduced the risk of radiation
      induced neoplasms in most situations.

PMID- 9614903
TI  - [Could the evaluation of the cost of complications be a worthwhile means to
      improve radiotherapy?].
AB  - At the present time, the current improvement of technical and dosimetric aspects
      of radiation oncology has to be evaluated in terms of potential benefit for the
      patient and the society. For this last point of view, specially designed economic
      analyses must be performed in order to justify the number of resources involved
      by these technical improvements. If the question is how the current technical
      procedures could reduce the risk of undesirable side-effects, the response cannot
      be immediately drawn from the literature. This paper emphasizes the possibility
      to evaluate the role of side-effects as endpoints of economic analyses when using
      special models in medical decision making such as Markov's. Only few oncologic
      situations are reliable to properly analyze the relationship between
      sophisticated radiation techniques and the incidence of post-radiation
      complications. These situations should be selected when prospective economic
      analyses are planned in the field of radiation therapy.

PMID- 9614904
TI  - [Quality of life, medicine and society].

PMID- 9614905
TI  - Two cases of fibrocystic breast disease with polysomy 18 as the sole clonal
      cytogenetic abnormality.
AB  - In the present study, we describe the occurrence of numerical alterations of
      chromosome 18 in two cases of benign fibrous/fibrocystic tumors of the breast,
      both of which were studied by conventional cytogenetic investigations and one of
      which was additionally tested by fluorescence in situ hybridization with the use
      of an alphoid centromeric probe specific for chromosome 18. Case 1 showed a
      tetrasomy 18 in 2 of 33 metaphases as the only clonal chromosomal aberration.
      Case 2 revealed both trisomy and tetrasomy 18 as clonal alterations in metaphases
      and interphase nuclei.

PMID- 9614906
TI  - Detection of gains and losses in 18 meningiomas by comparative genomic
      hybridization.
AB  - Comparative genomic hybridization (CGH) was used to examine gains and losses in
      18 meningioma tumors that had been previously analyzed for loss of heterozygosity
      (LOH) at 22q12. Partial or complete losses were seen by CGH in only 9 of 18 cases
      on chromosome 22. This compares with 11 of 18 losses of single or more loci by
      LOH. The discrepancy in these results in probably explained by the increased
      sensitivity of LOH by using microsatellite markers that are able to detect small
      deletions, whereas losses on the order of 10-15 megabases are required for
      confident identification by CGH. There was no consistent pattern of gains or
      losses by CGH, including those tumors that lacked LOH at 22q12. In one tumor of
      interest in which CGH and LOH studies failed to demonstrate loss on chromosome
      22, CGH identified an area of amplification at 17q22-23.

PMID- 9614907
TI  - Altered patterns of DNA methylation on chromosomes from leukemia cell lines:
      identification of 5-methylcytosines by indirect immunodetection.
AB  - An immunodetection technique has been developed to map with high resolution the
      methylated sites of human chromosomes. We have used this method to define the
      methylated areas of chromosomes from normal donors and from leukemia cell lines.
      The chromosomes were exposed for a short time to UV light to induce mild
      denaturation. The methylated sites were detected in situ by using monoclonal
      antibodies against 5-methylcytosine (prepared in mouse), and fluorescein
      conjugated antimouse immunoglobulins. The chromosomes from normal cells exhibited
      a fluorescent pattern with RCT banding, although some differences from previously
      reported patterns could be detected. With this method we have been able to show
      the presence of two types of R-bands: High fluorescence R-band (HFR) and low
      fluorescence R-band (LFR). Chromosomes from leukemia cell lines exhibited low
      global staining with disrupted RCT banding of the chromosomes. The decreased
      level of the methylation status of the chromosomes from leukemia cells was
      confirmed by detection of 5-methylcytosines on total immobilized DNA. Thus, we
      have shown that this method can be used to determine the methylated status of
      chromosomes and, in turn, to map not only the structural (banding) but also the
      functional (methylation status) properties of the different chromosome domains in
      normal and pathologic human cells.

PMID- 9614908
TI  - Abnormalities of chromosomes 8, 11, 14, and X in T-prolymphocytic leukemia
      studied by fluorescence in situ hybridization.
AB  - Twenty-one patients with T-prolymphocytic leukemia (T-PLL) were studied by FISH
      to characterize abnormalities of chromosomes 8, 11, 14, and X. A higher
      percentage of abnormalities of these chromosomes was detected by FISH than by
      cytogenetics. Seventy-one percent had inv(14) (q11q32)/t(14;14)(q11;q32). Four
      patients had abnormalities involving Xq28 (MTCP-1 locus) resulting from
      t(X;14)(q28;q11) or t(X;7)(q28;q35). These abnormalities have also been described
      in persistent expanding pre-malignant T-cell clones in patients with ataxia
      telangiectasia (AT). We have previously reported that in T-PLL and AT developing
      T-cell leukemia, the above abnormalities occur with additional abnormalities,
      mainly trisomy for 8q resulting predominantly from an i(8)(q10) and an increased
      expression of MYC. In this series, 81% of cases had chromosome 8 abnormalities
      including i(8)(q10)[43%]/t(8;8)(p12;q11)[14%], + 8[14%], and 8p + [14%]. The use
      of probes for MYC (8q24) and chromosome 8 centromere on metaphase chromosomes
      revealed that cases with i(8)(q10) were dicentric and t(8;8) monocentric. These
      abnormalities are not only associated with increase in dosage of 8q and the MYC
      gene, but also involved 8p. 8p is known to have several suppressor genes
      associated with solid tumors. Our findings suggest that the possible loss of a
      tumor suppressor gene plus the increased dosage of the q arm and/or the high
      expression of TCL-1/MTCP-1, which results from inv(14)/t(14;14), allows the
      malignant phenotype to emerge.

PMID- 9614909
TI  - Detection of RB1 deletions by fluorescence in situ hybridization in malignant
      hematologic disorders.
AB  - We evaluated the usefulness of fluorescence in situ hybridization (FISH) using
      different-colored commercial RB1 and 13qter DNA probes to identify RB1 deletions
      in interphase nuclei of bone marrow from 24 patients with agnogenic myeloid
      metaplasia (AMM), 20 patients with multiple myeloma (MM), 21 patients with other
      hematologic malignancies, and 25 normal bone marrow transplant (BMT) donors.
      Based on the 25 normal BMT donors, the upper boundary for the normal percentage
      of nuclei with one RB1 signal was 6.5%. Based on eight specimens known to have a
      deletion of 13q14 by cytogenetic studies, the lower limit of abnormal for the
      percentage of nuclei with one RB1 signal was 12.5%. More than 12.5% of nuclei had
      a single RB1 signal in 7/24 (29%) patients with AMM and 3/20 (15%) patients with
      MM. None of the 21 patients with hematologic malignancies other than AMM or MM
      had more than 12.5% nuclei with loss of RB1. The results of this study suggest
      that FISH with RB1 probes is useful to detect loss of RB1 in interphase nuclei
      from patients with hematologic disorders who have chromosome abnormalities
      involving 13q14. Thus, FISH with probes for RB1 is efficacious to investigate the
      pathogenesis of RB1 in malignant neoplasms and is a useful adjunct to
      conventional cytogenetic studies in clinical practice when abnormalities of 13q14
      are involved.

PMID- 9614910
TI  - A near-haploid bone marrow karyotype in systemic mast cell disease: is it
      characteristic of the disease or an incidental finding?
AB  - We present the case of a 40-year-old man with aggressive systemic mast cell
      disease. The patient had a predominant near-haploid clone in his bone marrow
      cells, detected by cytogenetic analysis performed at the time of diagnosis. The
      similarities between this case and a previously published case of near-haploidy
      in a patient with malignant mastocytosis suggest that near-haploidy may be a
      characteristic of aggressive systemic mast cell disease rather than an incidental
      finding.

PMID- 9614911
TI  - Trisomy 10 survival: a literature review and presentation of seven new cases.
AB  - Trisomy 10 as the only chromosome aberration is a rare phenomenon in malignant
      and premalignant hemopoietic disorders. We describe 7 new cases and have found
      another 12 in the literature. It appears that, whereas adult patients have
      myeloid disorders (acute myeloid leukemia, myeloproliferative, or myelodysplastic
      syndromes), in children the diagnosis is lymphocytic leukemia or lymphoma. The
      median survival was 122 months in the total material. Age above 60 years proved
      to be a significant adverse factor (median survival only 5 months; p = 0.003).
      None of the other clinical, cytogenetic, or hematological variables were of
      demonstrable prognostic importance. In contrast with the larger trisomy 10
      clones, those of limited size were associated with nonleukemic diagnoses, normal
      or slightly elevated leukocyte counts, and few or no circulating blasts. This may
      suggest that expansion of the trisomy 10 clone is associated with clinical and
      hematological progression.

PMID- 9614912
TI  - Translocation (3;16)(q27;p11) in a patient with diffuse large B-cell lymphoma
      associated with the BCL-6 gene rearrangement.
AB  - A patient with B-cell lineage diffuse large-cell lymphoma carrying the
      t(3;16)(q27;p11) and BCL-6 rearrangement is described. Cytogenetic studies showed
      46,XY,t(3;16)(q27;p11.2)[.11]/46,idem,add(18)(q21)[7]/46,XY[2]. The chromosomal
      translocation involving the 3q27 locus was associated with the BCL-6 gene
      rearrangement identified by Southern blot analysis. This case involved systemic
      lymph nodes, as large as 3 cm in diameter, bilaterally in neck, axilla, and
      inguinal regions. The patient obtained complete remission with chemotherapy.

PMID- 9614913
TI  - Translocation (3;13)(q27;q14): a nonrandom and probably secondary structural
      change in non-Hodgkin lymphomas.
AB  - Three cases of (3;13)(q27;q14) translocation observed in different histological
      types of non-Hodgkin lymphomas (NHLs) are reported here. This new recurring
      translocation in NHL was secondary in at least two of the patients because it was
      associated with another specific change [i.e., t(8;14) (q24;q32) in Burkitt
      lymphoma and t(14;18)(q32;q21) in typical follicular lymphoma]. In two of the
      cases for which molecular analysis was performed, a rearrangement of the LAZ
      3/BCK-6 gene was found.

PMID- 9614914
TI  - Spontaneous breakage and fragile site expression in chronic lymphocytic leukemia.
AB  - It has been suggested that genetic predisposition to cancer might be related to
      spontaneous chromosome instability or to fragile site expression. Therefore,
      spontaneous breakage and fragile sites were analyzed in nine untreated chronic
      lymphocytic leukemia (CLL) patients to determine their relation to cancer
      rearrangements. Five cases presented spontaneous gaps and breaks with a random
      distribution of breakpoints. In cultures treated with fluorodeoxyuridine or
      aphidicolin, 29 specific bands could be defined as fragile sites. A significant
      clustering of these sites was found with known common fragile sites (c-fra) and
      cancer breakpoints described in the literature. Most of these cancer breakpoints
      were involved in structural abnormalities associated with CLL (p < 0.00001).
      These data suggest that the expression of specific fragile sites might be related
      to structural chromosomal aberrations in CLL.

PMID- 9614915
TI  - Somatic DNA alterations in breast carcinomas of different lymph-node status by
      DNA fingerprint analyses.
AB  - The purpose of this study was to screen for somatic changes in invasive breast
      tumors by multilocus DNA fingerprints comparing normal (blood) and malignant
      tissue samples from 34 patients. The comparison of lymph node-positive and node
      negative breast carcinomas was of primary interest. After restriction enzyme
      digestion with HinfI and HaeIII, altered banding patterns were detected by using
      the oligonucleotide probe (GTG)5 in 7 of 34 (20.5%) and in 3 of 34 (8.8%) tumors
      after hybridization with (GACA)4. The overall frequency of changes thus amounted
      to 29.4%. Because long (GACA)n repeat motifs, generating predominant DNA
      fingerprint bands, are localized on the short arms of the human acrocentric
      chromosomes, sequences that are important in breast carcinogenesis may be present
      in these regions. The overall methylation status of the DNA does not appear to be
      responsible for DNA fingerprint differences, as can be demonstrated with the
      restriction endonuclease HaeIII. DNA fingerprint differences did not correlate
      with tumor grade, stage, and hormone receptor status. Tumors with lymph-node
      metastases expressed DNA fingerprint differences more frequently.

PMID- 9614916
TI  - E1A transformed normal human prostate epithelial cells contain a 16q deletion.
AB  - The difficulty of maintaining long-term prostate cell cultures has hindered the
      development of essential models for understanding prostate cancer. We report here
      the establishment of two 12S E1A transformed non-tumorigenic prostate epithelial
      cell strains, and their characterization. The two clonal cell strains, TP2 and
      TP4, proliferated for approximately 40 passages before senescence. Both exhibited
      a strong dependence on exogenous peptide growth factors and an immunophenotype
      characteristic of their prostate epithelial origin. Cytogenetic analysis revealed
      a consistent deletion on the q arm of chromosome 16 in TP2 with an otherwise
      normal karyotype. Band-specific microdissection generated region-specific probes
      from 16q23, which when used in fluorescence in situ hybridization (FISH) revealed
      that the region was deleted in 83% of metaphases analyzed. By cytogenetic
      analysis and FISH, the q arm of 16 was found deleted from the genome of TP4 in
      60% of cells analyzed. Lost sequences on 16q-16q23 in particular--in prostate
      cancer have been observed by a variety of methods. Localization of common region
      of deletion has been determined from these studies to be distal to 16q23. Our
      findings suggest that 16q23 may be of major importance in the development of
      prostate cancer, and may harbor tumor suppressor elements.

PMID- 9614917
TI  - Pentasomy of chromosome 8 in chronic myelomonocytic leukemia.

PMID- 9614918
TI  - A cytogenetic study of a cardiac papillary fibroelastoma.

PMID- 9614919
TI  - Characterization of 5q deletions by subtelomeric probes and spectral karyotyping.

PMID- 9614920
TI  - Insertion (11;7) in myelodysplastic syndrome.

PMID- 9614921
TI  - Intron 3 of HMGIC is the most frequent target of chromosomal aberrations in human
      tumors and has been conserved basically for at least 30 million years.

PMID- 9614922
TI  - A new case of nodular goiter with t(5;19)(q13;q13)

PMID- 9614923
TI  - Translocation (7;17)(q22;p13) as a sole karyotypic change in an adrenal adenoma.

PMID- 9614924
TI  - The role of TGF beta in the pathogenesis of human tuberculosis.

PMID- 9614925
TI  - Resistance to PGE2 inhibition of PWM-stimulated lymphocytes from neoplastic
      patients.
AB  - PGE2 treatment of mononuclear cells from patients with different types of
      neoplasias was unable to decrease either the number of plaque-forming cells or
      the expression of CD71 and CD25 in PWM-driven cultures. In contrast, in previous
      studies, PGE2 inhibited these parameters in cultured mononuclear cells from
      normal volunteers. Surgical treatment of cancer patients did not modify the
      lymphocyte sensitivity to PGE2 after 1 week, but at 2 and 6 months after
      therapeutical treatment, the inhibition values of the parameters studied were
      almost similar or very similar to those of normal lymphocytes. The reduction of
      PGE2 sensitivity in cancer patients was related to the increase of PGE2 levels
      and, probably, to a PGE2 receptor saturation. A restoration of PGE2-induced
      inhibition some months after therapy could be due to the decrease in PGE2 levels
      and to receptor unsaturation.

PMID- 9614926
TI  - Immune response to an epitope of the NS4 protein of hepatitis C virus in HCV
      related disorders.
AB  - NS4, a nonstructural protein of HCV, is a frequent target of antibodies in
      infected subjects. According to recent data, the antibodies frequently recognize
      the sequence 1921-40 of the NS4 protein. The aim of this work was to analyze
      antibody reactivity with the sequence 1921-40 in different HCV-related disorders.
      Although this sequence is located in a relatively invariant region of viral
      genome, two strain-specific sequences are described. Thus, three NS4 1921-1940
      peptides were synthesized: the BK shared by most viral strains, the J6 (strain
      2a), and the J8 (strain 2b). The peptides were used as antigens in the solid
      phase for measuring serum IgG antibodies in an ELISA assay. Antibodies reactive
      with the 1921-40 BK peptide were detected in 64% of sera from patients with
      autoimmune hepatitis (AIH), 51% from chronic hepatitis C (CHC), and 22% from
      mixed cryoglobulinemia (MC). The frequency of positive sera in MC was
      significatively lower than in AIH (P < 0.0001) or CHC (P < 0.0021). Similar
      results were obtained with the J6 and J8 peptides. All sera that did not react
      with the BK peptide were negative on J6 and J8 and conversely most sera reacting
      with the BK peptide also bound the J6 and the J8 peptides. No correlation was
      found between the genotype of the infecting virus and the presence of antibodies
      to any of the NS4 peptides. These results indicate that many HCV-infected
      subjects produce antibodies to the NS4 sequence 1921-40. The immune response to
      this sequence is not strain specific and varies with the different disorders
      associated with HCV infection.

PMID- 9614927
TI  - Cross-reacting idiotypes on anti-insulin autoantibodies in autoimmune diseases,
      identified by monoclonal antibodies.
AB  - Investigations on the specific idiotypes of autoantibodies are supposed to help
      with the understanding of the control mechanisms participating in the
      pathogenesis of autoimmune diseases. This study describes three monoclonal
      antibodies (Mabs) that recognize distinct idiotypic determinants on anti-insulin
      autoantibodies. The preabsorption by IAA-positive sera of insulin inhibits their
      subsequent binding to the anti-Id, thus suggesting that the Mabs recognize
      epitopes located at or near the binding site of insulin autoantibodies (IAA).
      These idiotypes are detected in sera from patients with insulin-dependent
      diabetes mellitus (IDDM), which are IAA-negative, also. It is possible that the
      expression of the idiotypes recognized might generally be associated with
      induction of autoantibodies, since they were found in sera from patients with
      rheumatoid arthritis (RA), autoimmune thyroid disease (AITD), and cataract (K).
      It can be assumed that the corresponding idiotypes of these Mabs, or similar
      structures (sequential or conformational), are expressed on autoantibodies with
      various antigen-binding specificities. These data suggest that some autoimmune
      diseases are preceded by the secretion of autoantibodies which express a common
      or similar pathological idiotype.

PMID- 9614928
TI  - Prognostic value of MIP-1 alpha, TGF-beta 2, sELAM-1, and sVCAM-1 in patients
      with gram-positive sepsis.
AB  - The aim of the present study was to evaluate the potential prognostic value of
      MIP-1 alpha, TGF-beta 2, sELAM-1, and sVCAM-1 in patients with gram-positive
      sepsis. Twenty-eight patients with gram-positive sepsis were compared to 11
      patients with gram-negative sepsis and 15 healthy volunteers. Sepsis was defined
      by the criteria of Bone et al. (Crit. Care Med. 21, 5447-5463, 1993) and by
      isolation of at least two positive blood cultures with gram-positive/gram
      negative bacteria. Plasma samples for determination of the immunological
      parameters were collected daily. Analysis of cytokines and adhesion molecules was
      performed on days 0 (day of sepsis criteria fulfillment), 4, and 7 (or 1 day
      before death). In the gram-positive group 10 of 28 patients died; in the gram
      negative group 4 of 11 died. Only sELAM-1 plasma concentrations were found to be
      a useful early parameter in predicting patients' outcome in gram-positive sepsis.
      sELAM-1 concentrations at the onset of the study (day 0) were significantly
      higher in the nonsurviving patients than those in the survivors. MIP-1 alpha
      levels were significantly higher only on days 4 and 7. With regard to the
      measured plasma concentrations we believe that MIP-1 alpha is not a useful
      parameter for predicting patients' prognosis. The increase of sVCAM-1 might play
      a role in the pathogenesis of gram-positive sepsis; however, it could not be
      relied upon as an early prognostic parameter. The potential role of TGF-beta 2 in
      the development of gram-positive sepsis could not evaluated in the present study,
      whereas routine measurements of TGF-beta 2 offered no additional prognostic
      information.

PMID- 9614929
TI  - Fasciola hepatica-induced immune suppression of spleen mononuclear cell
      proliferation: role of nitric oxide.
AB  - The aim of the present study was to evaluate the proliferative response of spleen
      mononuclear cells (Spm) to mitogens in rats infected with Fasciola hepatica and
      its correlation with Spm and peritoneal cell (PC) nitric oxide (NO) production on
      Days 1, 3, 7, 14, 30, and 60 postinfection. In addition, histological changes in
      the liver were also studied. The proliferative response to Con A of F. hepatica
      infected Spm was significantly decreased on Day 7 postinfection (P < 0.01).
      However, a pronounced increase of the proliferative response was detected from
      Day 3 until Day 60 when Spm were stimulated with LPS. In order to determine
      whether NO levels were modified during F. hepatica infections, we quantified
      nitrite in Spm and PC supernatants in cultures. Our results indicate a profound
      decrease of nitrite production by LPS-stimulated PC on the first and second weeks
      postinfection, and an increase in the levels of this mediator on LPS-stimulated
      Spm at the same postinfection time. The F. hepatica excretory-secretory antigen
      (ESA) was in part involved in the decrease of nitrite production by LPS
      stimulated PC. A mechanism to avoid an immune response during the first stages of
      liver penetration could explain the transient suppression observed in Spm
      proliferative responses. On the other hand, the decrease in NO production by rat
      infected PC could also be one of the strategies of the parasite to avoid the
      potential killing effect of NO during peritoneal migration.

PMID- 9614930
TI  - Inflammatory potential of C-reactive protein complexes compared to immune
      complexes.
AB  - C-reactive protein (CRP) is an acute phase serum protein that binds to
      phosphocholine (PC) and to components of damaged tissue. CRP resembles antibody
      in that it binds to ligands and activates the classical complement pathway. To
      compare the processing of CRP complexes to that of IgG complexes, we have
      prepared complexes containing the same ligand, PC-conjugated BSA, and IgG
      antibody to either BSA or CRP. We previously demonstrated similar complement
      mediated binding of these complexes to erythrocyte complement receptors. CRP and
      IgG also bind to receptors on neutrophils (PMN), providing another possible
      pathway for clearance of ligands. PMN binding of IgG complexes can lead to
      activation with damaging inflammatory consequences. In the present report we have
      used CRP and IgG complexes containing PC-BSA to compare binding to PMN and
      activation of PMN adherence to endothelial cells. The results indicate that CRP
      complexes do not activate PMN whereas IgG complexes do. Binding assays indicate
      that there is substantially greater binding of IgG than CRP complexes to PMN.

PMID- 9614931
TI  - Morphine enhances complement receptor-mediated phagocytosis of Cryptococcus
      neoformans by human microglia.
AB  - Recent studies have shown that opiates modulate the function of microglia, the
      resident macrophages of the brain. In this study, the effect of morphine on
      phagocytosis by human fetal microglial cells of the opportunistic fungus
      Cryptococcus neoformans was studied. Contrary to earlier findings with swine
      microglia, opsonization was required for the phagocytosis of C. neoformans by
      human microglia. Moreover, morphine (10(-8)M) was shown to augment uptake of
      opsonized C. neoformans by over 50%. This contrasts with the earlier finding of
      morphine-induced inhibition of phagocytosis of nonopsonized cryptococci by swine
      microglia. The effect of morphine on cryptococcal phagocytosis by human microglia
      was reversed by treatment of microglial cells with mu opiate receptor antagonists
      as well as by addition of anti-complement receptor antibodies to the cell
      cultures, indicating that both the mu opiate receptor and the complement receptor
      are involved in morphine-enhanced phagocytosis. These findings support the
      concept of opiates as neuroimmunomodulatory agents and demonstrate that the
      effects of opiates on microglial cells may be influenced by the animal species
      from which the cells are derived.

PMID- 9614932
TI  - Elevated CD69 expression on naive peripheral blood T-cells in hyperthyroid
      Graves' disease and autoimmune thyroiditis: discordant effect of methimazole on
      HLA-DR and CD69.
AB  - This study investigated T-cell activation markers HLA-DR and CD69 in both naive
      (CD45RA+) and memory (CD45RA-) CD4+ as well as CD8+ T cells in peripheral blood
      of patients with autoimmune thyroiditis (AT, N = 28) or hyperthyroid untreated
      Graves' disease (GDH, N = 34) using three-color flow cytometry. It was
      demonstrated that patients with AT, but not those with GDH, expressed increased
      amounts of HLA-DR antigen compared to healthy subjects (HS, N = 26) on total CD4+
      (AT: 14.1%; GDH: 11.3%; HS: 10.9%) and CD8+ cells (AT: 31.9%; GDH: 23.5%; HS:
      19.4%) as well as on CD45RA- CD4+ cells (AT: 11.2%; GDH: 7.7%; HS: 7.9%). In GDH
      (+71%) and AT (+91%) only the proportion of HLA-DR+ CD45RA+ CD8+ cells was
      increased vs HS. Furthermore, euthyroid GD patients on methimazole (GDE, N = 22)
      displayed greater HLA-DR+ expression on total and CD45RA- cells within both CD4+
      (+37 and 40%, respectively) and CD8+ cells (+47 and 93%, respectively) than GDH.
      In addition, total and CD45RA+ CD4+ and CD8+ cells were increased vs HS. In
      contrast, proportions of CD69 positive T cells were increased in AT and GDH on
      total CD4+ (+97 and 74%, respectively) and CD8+ (+95 and 68%, respectively) cells
      and all subsets thereof (except for CD45RA- cells in GDH), but normalized upon
      thyrostatic treatment. We conclude that patients with autoimmune thyroid disease
      harbor an almost twofold greater proportion vs HS of (a) HLA-DR+ CD45RA+ CD8+ T
      cells, and of (b) CD69 on total CD4+ and CD8+ cells, and an even more marked
      elevation on their CD45RA+ subset in AT and untreated GD. In addition, (c)
      thyrostatic treatment by methimazole in GD is accompanied by a further increase
      in circulating HLA-DR+ CD4+ and CD8+ cells and their CD45RA- subsets, but
      decreased CD69 expression. These data suggest association of HLA-DR expression
      with ongoing autoimmunity, while increased CD69 expression relates in part also
      to elevated thyroid hormone concentration in GDH.

PMID- 9614933
TI  - Analysis of complement receptor type 1 (CR1) expression on erythrocytes and of
      CR1 allelic markers in Caucasian and African American populations.
AB  - CR1 expression on erythrocytes (E) is regulated by an element that is tightly
      linked in Caucasians to the site of an RFLP of the CR1 gene. Genomic HindIII
      fragments of 7.4 and 6.9 kb identify alleles that are expressed in high (H
      allele) or low (L allele) amounts, respectively. When age-fractionated E of
      donors heterozygous for both the H and L alleles and for CR1 allotypes of
      differing molecular weights were analyzed in Western blots, the product of the L
      allele appeared to have an increased rate of loss during cell aging. A coding
      sequence polymorphism of CR1 predicted to cause a Pro-->Arg substitution in its
      proximal extramembranous region was tightly linked in Caucasians to the site of
      the HindIII RFLP. However, neither this polymorphism nor the HindIII RFLP
      correlated with CR1 expression among African Americans. Relative instability of
      CR1 encoded by the L allele thus may derive from another coding sequence
      polymorphism, or may require both the Pro-->Arg substitution and epistatic
      effects of another polymorphic gene.

PMID- 9614934
TI  - Myosin-reactive autoantibodies in rheumatic carditis and normal fetus.
AB  - EBV-transformed B cells from a 20-week human fetal spleen and from blood of
      patients with poststreptococcal rheumatic carditis were studied. Most antibodies
      from nine fetal and six patient myosin-reactive B cell clones were multireactive
      (reacting with cardiac myosin, Streptococcus pyogenes, and rat cardiac myocytes)
      which supports a role for molecular mimicry in stimulation of these
      autoantibodies. Sequence analysis revealed that fetal and patient anti-myosin
      repertoires were composed of unrelated clones with diverse V gene usages. Fetal
      and patient antibodies had reduced VH CDR3 length on average and reduced light
      chain N region addition with a low rate of somatic mutation in the variable
      region genes, characteristics generally associated with fetal B cells but also
      with some adult B cells. Five of six myosin-reactive patient clones used VH3,
      whereas only two of nine fetal clones used VH3, suggesting skewing from the
      average 50-60% VH3 gene usage found in randomly selected adult and fetal
      antibodies.

PMID- 9614935
TI  - Complement C1q inhibits cellular spreading and stimulates adenylyl cyclase
      activity of fibroblasts.
AB  - C1q selectively localizes at injured tissues, where it may function as a
      regulator of cell-matrix interactions. We show here that purified C1q, added to
      the culture medium of human gingival fibroblasts (HF) spread onto fibronectin
      substrates, elicited a round morphology that was accompanied by altered F-actin
      and correlated with inhibition of cellular spreading. Shape modification required
      integrity of the molecule and was specific, dose dependent, nontoxic, and
      reversible. Antispreading activity was mediated, at least in part, by specific
      cell-surface C1q receptors. We hypothesized that ligand occupancy of C1q
      receptors could influence shape by affecting intracellular levels of cyclic AMP
      (cAMP). Within 20 min of exposure of adhering HF to C1q, we detected an increase
      in adenylyl cyclase activity (six- to ninefold) in cAMP accumulation (by 20%) and
      in cAMP-dependent protein kinase activity (by 20%). These changes suggested that
      the rounding effect of C1q may be associated with activation of the adenylyl
      cyclase pathway.

PMID- 9614936
TI  - An atomic model of crystalline actin tubes: combining electron microscopy with X
      ray crystallography.
AB  - The packing of the G-actin monomers within crystalline actin tubes was
      investigated at atomic detail. To achieve this, we have chosen an integrated
      structural approach which combines intermediate resolution electron microscopy
      based 3-D reconstruction and surface metal shadowing of crystalline actin tubes
      with atomic resolution X-ray data of the G-actin monomer. Distinct from the
      parallel, half-staggered packing of the actin subunits within F-actin filaments,
      the arrangement of actin monomers within the crystalline tubes involves
      antiparallel packing into dimers with p2 symmetry. Within the crystalline tubes,
      the actin monomers are oriented so that the filament axis runs parallel with the
      sheet plane and the intersubunit contacts in this direction are similar to those
      existing along the two long-pitch helical strands of the F-actin filament. The
      other intersubunit contacts within the crystalline tubes are not found in the
      actin filament. The ability of actin to form a variety of polymorphic oligomers
      is still not fully understood, and the functional implications of this
      variability have yet to be deciphered. Regularly packed actin assemblies such as
      sheets, tubes or ribbons may ultimately yield structural relationships to in vivo
      relevant actin oligomers such as, for example, the "lower dimer".

PMID- 9614937
TI  - Different conformations of nascent peptides on ribosomes.
AB  - The length at which the N terminus of nascent proteins becomes available to
      antibodies during their synthesis on ribosomes was determined. Three different
      proteins, bovine rhodanese, bacterial chloramphenicol acetyltransferase and MS2
      coat protein, were synthesized with coumarin at their N terminus in a cell-free
      system derived from Escherichia coli. A derivative of coumarin was
      cotranslationally incorporated as N-coumarin-methionine at the N terminus of
      polypeptides. The interaction of specific anti-coumarin antibodies with this N
      terminal coumarin of ribosome-bound nascent peptides was examined. The results
      indicate that short nascent peptides of each of the three proteins are
      unreactive, that the length at which they become accessible to the antibodies is
      different for the three proteins, and that longer peptides differ in their
      reactivity. It is suggested that these differences are due to differences in the
      conformation acquired by the peptides as they are synthesized on the ribosomes.

PMID- 9614938
TI  - The mouse mammary tumour virus promoter positioned on a tetramer of histones H3
      and H4 binds nuclear factor 1 and OTF1.
AB  - Modulation of eukaryotic gene expression is influenced by the organization of
      regulatory DNA-elements in chromatin. The mouse mammary tumor virus (MMTV)
      promoter exhibits regularly positioned nucleosomes that reduce the accessibility
      of the binding sites for sequence-specific transcription factors, in particular
      nuclear factor (NF1). Hormonal induction of the MMTV promoter is accompanied by
      remodeling of the nucleosomal structure, but the biochemical nature of these
      structural changes is unknown. Using recombinant histones, we have now assembled
      the MMTV promoter in particles containing either an octamer of the histones H3,
      H4, H2A and H2B or a tetramer of histones H3 and H4, and have compared the two
      particles in terms of structure, positioning, and exclusion of transcription
      factors. Using site-directed hydroxy radicals to map histone locations, two main
      nucleosome positions are found with dyads at position -107 and at -127. The same
      two main positions are found for particles containing only the H3/H4 tetramer,
      showing that the absence of H2A/H2B dimers does not alter positioning. The
      rotational orientation of the DNA double helix in both types of particles is
      essentially identical. However, the ends of the nucleosomal DNA as well as its
      central region are more accessible to cleavage reagents in the tetramer particle
      than in the octamer particle. In agreement with these structural features, the
      transcription factors NF1 and OTF1 were able to bind to their cognate sites on
      the tetramer particle, while they could not gain access to the same sites on the
      surface of the octamer particle. The DNase I digestion pattern of octamers
      treated with partially purified SWI/SNF complex from HeLa cells in the presence
      of ATP is indistinguishable from that of tetramer particles, suggesting that the
      SWI/SNF complex promotes ATP-dependent remodeling of the octamer particle but not
      of tetramer particles. These results are compatible with a hormone-induced
      removal of histone H2A/H2B during MMTV induction.

PMID- 9614939
TI  - Phi 29 DNA polymerase requires the N-terminal domain to bind terminal protein and
      DNA primer substrates.
AB  - A 44 kDa C-terminal fragment of phi 29 DNA polymerase has been separately
      expressed and purified from Escherichia coli cells. As expected, the truncated
      protein lacked the 3'-5' exonuclease activity and strand-displacement capacity,
      previously mapped in the N-terminal domain of phi 29 DNA polymerase. On the other
      hand, the 44 kDa C-terminal fragment retained polymerase activity when using Mn2+
      as metal activator, although the catalytic efficiency was greatly reduced with
      respect to that of the complete enzyme. Moreover, and in contrast to the high
      processivity exhibited by phi 29 DNA polymerase (> 70 kb), polymerization by its
      C-terminal domain was completely distributive. All these polymerization defects
      were related to a strong impairment of DNA binding, suggesting that additional
      contacts present in the N-terminal domain are important for an optimal
      stabilization and translocation of the DNA during polymerization. Moreover, the C
      terminal domain showed a very reduced capacity to initiate terminal protein (TP)
      primed DNA replication, as a consequence of a weakened interaction with the TP
      primer, and a lack of activation by protein p6, the initiator of phi 29 DNA
      replication. We conclude that the C-terminal portion of phi 29 DNA polymerase
      (residues 188 to 575), although having a structural entity as the domain
      responsible for the synthetic activities, requires the N-terminal domain to
      provide important contacts for the two different substrates, DNA and TP, that
      prime DNA synthesis. These results support the hypothesis of a modular
      organization of enzymatic activities in DNA-dependent DNA polymerases, but
      emphasize the functional coordination required for coupling DNA synthesis and
      proofreading, and for the more specific functions (TP-priming, high processivity
      and strand-displacement) inherent to phi 29 DNA polymerase.

PMID- 9614940
TI  - Chimeric HIV-1 and feline immunodeficiency virus reverse transcriptases: critical
      role of the p51 subunit in the structural integrity of heterodimeric lentiviral
      DNA polymerases.
AB  - The reverse transcriptase (RT) of HIV-1 and feline immunodeficiency virus (FIV)
      consist of two subunits of 51 kDa (p51) and 66 kDa (p66). In order to elucidate
      the role of p51 in the heterodimer, chimeric HIV-1/FIV RT heterodimers were
      constructed and characterized. The FIV RT p51/HIV-1 RT p66 chimera showed a 2.5
      fold higher RNase H activity than the natural HIV-1 RT, a 50% lower strand
      displacement DNA synthesis activity and resistance to the two RT inhibitors 3'
      azido-3'-deoxythymidine triphosphate (AZTTP) and Nevirapine. The HIV-1 RT p51/FIV
      RT p66 chimera on the other hand had very similar properties to the natural FIV
      RT. The differences observed upon exchange of the p51 subunits suggest that the
      three-dimensional structure of the p51 subunit in the RT heterodimers is not
      completely conserved between the human and the feline lentiviruses. Finally, our
      data suggest an important role for the p51 subunit in maintaining the optimal
      structural integrity of the RT heterodimer. The different effects of the small
      subunits on the sensitivity to known RT inhibitors might be of importance in the
      development of novel drugs against HIV-1 RT.

PMID- 9614941
TI  - RNA determinants of a specific RNA-coat protein peptide interaction in alfalfa
      mosaic virus: conservation of homologous features in ilarvirus RNAs.
AB  - Alfalfa mosaic virus (AMV) coat protein and tobacco streak virus (TSV) coat
      protein bind specifically to the 3' untranslated regions of the viral RNAs and
      are required with the genomic RNAs to initiate virus replication. A combination
      of nucleotide substitutions, hydroxyl radical footprinting, and ethylation and
      chemical modification interference analysis has been used to define the RNA
      determinants important for the specific binding of the 3'-terminal 39 nucleotides
      of AMV RNA 3/4 (AMV843-881) to an amino-terminal coat protein peptide (CP26). The
      results demonstrate that potential phosphate and base-specific contacts as well
      as ribose moieties protected upon peptide binding cluster in lower hairpin stems
      and flanking AUGC sequences of the viral RNA, without direct involvement of loop
      nucleotides. Nucleotides identified in the modification-interference analyses as
      important for RNA-protein interactions are highly conserved among AMV and the
      ilarvirus RNAs. This RNA sequence homology, coupled with the recent
      identification of an RNA binding consensus sequence for AMV and ilarvirus coat
      proteins, provides a framework for understanding the functional equivalence of
      AMV and TSV coat proteins in binding RNA and activating virus replication and may
      explain why heterologous AMV and ilarvirus coat protein-RNA mixtures are
      infectious.

PMID- 9614942
TI  - A map of the biotin repressor-biotin operator interface: binding of a winged
      helix-turn-helix protein dimer to a forty base-pair site.
AB  - The Escherichia coli biotin repressor is a member of the "winged helix-turn
      helix" class of site-specific DNA binding proteins. The protein binds as a dimer
      to the 40 bp biotin operator sequence. Although the structure of the aporepressor
      has been solved by X-ray crystallographic techniques, no structure of the
      holorepressor-DNA complex is yet available. In order to characterize the
      structural features of the biotin repressor-biotin operator interface we have
      applied a number of solution techniques including DNase I, hydroxyl radical and
      dimethyl sulfate footprinting and the circular permutation or "bending" assay.
      Results of these combined studies indicate that each repressor monomer forms a
      bipartite interface with each half-site of the biotin operator sequence. The
      results imply that, in addition to the helix-turn-helix module of each monomer, a
      second structural element participates in the protein-DNA interface. The two
      bipartite protein-DNA interfaces appear, moreover, to primarily involve the two
      12 bp termini of the operator site. Results of combined DNase I footprinting and
      circular permutation analysis indicate, furthermore, that the central 16 bp
      region that links the two termini becomes distorted concomitant with binding of
      holoBirA.

PMID- 9614943
TI  - tRNA anticodon recognition and specification within subclass IIb aminoacyl-tRNA
      synthetases.
AB  - Subclass IIb aminoacyl-tRNA synthetases (Asn-, Asp- and LysRS) recognize the
      anticodon triplet of their cognate tRNA (GUU, GUC and UUU, respectively) through
      an OB-folded N-terminal extension. In the present study, the specificity of
      constitutive lysyl-tRNA synthetase (LysS) from Escherichia coli was analyzed by
      cross-mutagenesis of the tRNA(Lys) anticodon, on the one hand, and of the amino
      acid residues composing the anticodon binding site on the other. From this
      analysis, a tentative model is deduced for both the recognition of the cognate
      anticodon and the rejection of non-cognate anticodons. In this model, the enzyme
      offers a rigid scaffold of amino acid residues along the beta-strands of the OB
      fold for tRNA binding. Phe85 and Gln96 play a critical role in this spatial
      organization. This scaffold can recognize directly U35 at the center of the
      anticodon. Specification of the correct enzyme:tRNA complex is further achieved
      through the accommodation of U34 and U36. The binding of these bases triggers the
      conformationnal change of a flexible seven-residue loop between strands 4 and 5
      of the OB-fold (L45). Additional free energy of binding is recovered from the
      resulting network of cooperative interactions. Such a mechanism would not depend
      on the modifications of the anticodon loop of tRNA(Lys) (mnm5s2U34 and t6A37). In
      the model, exclusion by the synthetase of non-cognate anticodons can be accounted
      for by a hindrance to the positioning of the L45 loop. In addition, Glu135 would
      repulse a cytosine base at position 35. Sequence comparisons show that the
      composition and length of the L45 loop are markedly conserved in each of the
      families composing subclass IIb aminoacyl-tRNA synthetases. The possible role of
      the loop is discussed for each case, including that of archaebacterial aspartyl
      tRNA synthetases.

PMID- 9614944
TI  - Triple helix-directed psoralen crosslinks are recognized by Uvr(A)BC
      excinuclease.
AB  - Pyrimidine oligonucleotides bind to the major groove of an oligopyrimidine
      oligopurine DNA sequence by triple helix formation. A 14-mer oligopyrimidine 3'
      psoralen-conjugate (P) and a doubly modified 5'-acridine/3'-psoralen
      oligonucleotide (PA) were photo-crosslinked to their target site. The crosslinked
      complexes were tested regarding their sensitivity to Uvr(A)BC excinuclease/DNA
      complex formation and excision, and compared to free psoralen crosslinked to the
      same site (M). An electrophoretic mobility-shift assay showed that the
      crosslinked triple-helix did not hamper formation of the (A)2B complex under
      conditions where the third strand was bound to its target. In vitro excision
      experiments performed on damaged DNA fragments containing crosslinked 5
      methoxypsoralen (M-target) confirmed that the psoralen photoadduct was recognized
      by Uvr(A)BC and that excision occurred at the crosslinked site. The major
      cleavage reaction took place on the 5'-side of oligopurine strand. The excision
      was less efficient on the 5'-side of the pyrimidine strand. The 3'-side incision
      either on the purine or pyrimidine strand was even weaker. With optimal Uvr(A)
      concentrations, it was observed that the incision reaction on (P)- and (PA)
      modified targets was clearly inhibited compared to the (M)-modified target,
      reflecting an effect of the oligonucleotide on the recognition/excision process.
      These results demonstrate that a triple helix is efficient in promoting
      inhibition of Uvr(A)BC excision nuclease activity. These results could account
      for divergent findings concerning the effects of triple helix-forming
      oligonucleotides on repair systems and open new perspectives to study DNA repair
      processes through the use of bi-substituted triple helix-forming
      oligonucleotides.

PMID- 9614945
TI  - Sequence of the Octopus dofleini hemocyanin subunit: structural and evolutionary
      implications.
AB  - Sequencing of the subunit of the hemocyanin of Octopus dofleini has been
      completed from a cDNA library. This represents the first molluscan hemocyanin to
      be completely sequenced. The sequence determined is for one of the two
      distinguishable cDNAs which have been recognized for this protein. The protein
      subunit has 2896 amino acids and contains seven functional units, each carrying
      two sets of three invariant histidine residues constituting the binding sites (A
      and B) for two copper atoms. The accompanying paper identifies this site in the C
      terminal functional unit (Odg). Differences in sequence for the two cDNAs, for
      the region in which both are available, are concentrated in the "linker regions"
      between functional units. The sequences of the seven units exhibit high
      similarity, averaging about 40% identity, with a concentration of conserved
      sequences in the region surrounding the copper binding sites. The sequences
      around the B-site show significant homology to the sequences of arthropod
      hemocyanins. Comparison of the functional unit sequences in terms of
      hydrophobicity and surface exposure profiles, as well as regions of probable
      secondary structure, indicate that all functional units probably have a common
      tertiary folding; the protein subunit is a string of similarly folded beads. A
      number of putative N-linked carbohydrate binding sites can be recognized in the
      sequence; one of these corresponds to the carbohydrate observed in the X-ray
      diffraction study of functional unit Odg as disclosed in the accompying paper.
      Phylogenetic analysis of the sequences of the O. dofleini functional units, and
      comparison with other available molluscan sequences indicates that the multi
      domain subunit structure must have arisen over a relatively brief period,
      preceeding the differentiation of major molluscan types.

PMID- 9614946
TI  - The identification and characterization of microsatellites in the compact genome
      of the Japanese pufferfish, Fugu rubripes: perspectives in functional and
      comparative genomic analyses.
AB  - Fugu rubripes (Fugu) has one of the smallest recorded vertebrate genomes and is
      an economic tool for comparative DNA sequence analysis. Initial characterization
      of 128 kb of Fugu DNA attributed the compactness of this genome, in part, to a
      sparseness of repetitive DNA sequence compared with mammalian genomic sequences.
      This paper describes a new and comprehensive analysis in which 501 theoretically
      possible microsatellites with a repeat unit of one to six bases were used to
      query two orders of magnitude more Fugu DNA (i.e. 11.338 Mb). A total of 6042
      microsatellites were identified and categorized. In decreasing order, the 20 most
      frequently occurring microsatellites are AC, A, C, AGG, AG, AGC, AAT, AAAT, ACAG,
      ACGC, ATCC, AAC, ATC, AGGG, AAAG, AAG, AAAC, AT, CCG and TTAGGG. The 20 most
      frequently occurring microsatellites represent 81.79% of all microsatellites
      identified. Our results indicate that one microsatellite occurs every 1.876 kb of
      DNA in Fugu, 11.55% of the microsatellites are detected in open reading frames
      that are predicted protein coding regions. With respect to the proportion of
      microsatellites present in open reading frames and the total abundance (bp) of
      all microsatellites, the genome of Fugu is similar to the genome of many other
      vertebrate species. Previous estimates performed indicate that approximately 1%
      of many vertebrate genomes are comprized of microsatellite sequences. However,
      many differences prevail in the abundance and frequency of the individual
      microsatellite classes. Many of the frequently occurring microsatellites in Fugu
      are known to code in other species for regions in proteins such as transcription
      factors, whilst others are associated with known functions, such as transcription
      factor binding sites and form part of promoter regions in DNA sequences of genes.
      Therefore, it is likely that such repeats in genomes have a role in the evolution
      of genes, regulation of gene expression and consequently the evolution of
      species.

PMID- 9614948
TI  - On the global architecture of initiation factor IF3: a comparative study of the
      linker regions from the Escherichia coli protein and the Bacillus
      stearothermophilus protein.
AB  - Initiation factor IF3 is a protein involved in the initiation stage of protein
      synthesis. It consists of two global domains linked by a 20 residue long, solvent
      exposed linker. Recently, the structure of the N and C-terminal domains of the
      Bacillus stearothermophilus protein have been solved by X-ray crystallography and
      the structure of the intact Escherichia coli protein has been studied by NMR.
      These two studies have led to apparently contradictory models for the domain
      organization of IF3. The NMR study of the E. coli protein indicates that the
      linker region is flexible, while the studies of the isolated N and C-terminal
      domains of the B. stearothermophilus protein suggest that the linker forms a
      rigid helical rod. In order to resolve this discrepancy, a set of peptides
      corresponding to the linker regions of the B. stearothermophilus and the E. coli
      protein were synthesized. Circular dichroism and NMR spectroscopy were used to
      study the helical content as a function of pH, temperature, peptide concentration
      and ionic strength. Both peptides are monomeric. The estimated helical content of
      the linker fragment from B. stearothermophilus is 68% at high pH and 1 degree C.
      The measured helicity decreases to 53% at pH 7.0 and 1 degree C. In contrast, the
      peptide corresponding to the E. coli IF3 linker region is largely unstructured
      with a maximum helical content of 15% at high pH and only 8% at pH 7.0, 1 degree
      C. These results suggest that the different structures observed for the two
      intact proteins may be due to the different intrinsic stability of the two linker
      peptides. The helical content of the two linker peptides is, however, much closer
      when the peptides are compared at the respective temperatures of optimum growth
      for E. coli and B. stearothermophilus (3% versus 17%). The pH and ionic strength
      dependence of the helical content of the B. stearothermophilus peptide
      demonstrates that side-chain/side-chain interactions play an important role in
      stabilizing the helical structure. In addition, studies with mutant peptides show
      that the first Asp residue in the linker sequence helps to stabilize the helix
      via an N- capping interaction.

PMID- 9614947
TI  - Crystal structure of a functional unit from Octopus hemocyanin.
AB  - Hemocyanins are giant oxygen transport proteins found in many arthropods and
      molluscs. Freely dissolved in the hemolymph, they are multisubunit proteins that
      contain many copies of the active site, a copper atom pair that reversibly binds
      oxygen. Octopus hemocyanin is composed of ten subunits, each of which contain
      seven oxygen-binding "functional units". The carboxyl-terminal 47 kDa functional
      unit, Odg, is a proteolytic isolate that binds oxygen reversibly while exhibiting
      slight Bohr and magnesium ion effects. In this work we present the X-ray
      structure determination and analysis of Odg at 2.3 A resolution. Odg has two
      structural domains: a largely alpha-helical copper binding domain, and a five
      stranded anti-parallel beta-sandwich with the jelly roll topology found in many
      viruses. Six histidine residues ligate the copper atoms, one of which is involved
      in a thioether bridge. The results show that the hemocyanin from the mollusc and
      that from the arthropod have distinct tertiary folds in addition to the long
      recognized differences in their quaternary structures. Nonetheless, a comparison
      of Octopus and horseshoe crab hemocyanin reveals a similar active site, in a
      striking example of perhaps both convergent and divergent evolution.

PMID- 9614949
TI  - Anion-induced folding of Staphylococcal nuclease: characterization of multiple
      equilibrium partially folded intermediates.
AB  - The refolding of acid-unfolded staphylococcal nuclease (SNase) induced by anions
      was characterized, and revealed the existence of three different partially folded
      intermediates (A states). The three intermediates lack the rigid tertiary
      structure characteristic of native states, and differ in their degree of folding
      as measured by probes of secondary structure, size, stability and globularity.
      The least structured conformation, A1, is stabilized by chloride (600 mM) or
      sulfate (100 mM). It is about 50% folded (based on circular dichroism and small
      angle X-ray scattering (SAXS) data). The next most structured intermediate, A2,
      is induced by trifluoroacetate (300 mM) and has approximately 70% native-like
      secondary structure. The most structured intermediate, A3, is stabilized by
      trichloroacetate (50 mM) and has native-like secondary structure content and is
      almost as compact as the native state. The stability toward urea denaturation
      increases with increasing structure of the intermediates. Moreover, ureainduced
      unfolding studies show that these partially folded species are separated from
      each other, and from the unfolded state, by significant free energy barriers,
      suggesting that they are distinct conformational states. Kratky plots, based on
      the SAXS data, indicate that the two more structured intermediates have
      significant globularity (i.e. a tightly packed core), whereas the less structured
      intermediate has very little globularity. These observations support a model of
      protein folding in which certain conformations are of particularly low free
      energy and hence populated under conditions which differentially destabilize the
      native state. These partially folded intermediates probably consist of ensembles
      of substates with a common core of native-like secondary structure, which is
      responsible for their stability. Consequently, it is likely that the
      intermediates observed here represent the equilibrium counterparts of transient
      kinetic intermediates.

PMID- 9614950
TI  - [Locally advanced prostate carcinoma (T2b-T4 N0) without and with clinical
      evidence of local progression (Tx N+) with lymphatic metastasis. Is radiotherapy
      for pelvic lymphatic metastasis indicated or not?].
AB  - BACKGROUND: There is a greater controversy regarding the indication of
      radiotherapy of the pelvic lymphatics in patients with suspected lymph node
      metastases in locally advanced prostate cancer (T2b-4 N0) on the one hand and in
      patients with pathologically proven lymph node metastases in locoregional
      advanced prostate cancer (Tx pN+) on the other hand following definitive
      radiotherapy and radical prostatectomy. This paper investigates the possible
      indications for radiotherapy of the pelvic lymphatics in the light of data from
      the literature. PATIENTS AND METHODS: Because data from several retrospective
      studies concerning radiotherapy of the pelvic lymphatics indicated a better
      outcome, the RTOG conducted 2 prospective randomised studies (RTOG 75-06, 77-06)
      to address these questions. However, the results of these studies showed no
      better survival or cause specific survival for patients treated for the
      paraaortal or pelvic lymphatics and therefore, radiotherapy of the pelvic
      lymphatics was no more advocated. A reanalysis showed several problems of the
      study design and it was concluded that the studies couldn't prove the question of
      elective radiotherapy of the pelvic lymphatics. In RTOG 77-06 patients with
      T1b/T2 tumors were investigated. Therefore, there is no prospective study
      investigating the elective radiotherapy in patients with T3-tumors, who are at
      high risk of pelvic lymph node metastases. RESULTS: Today there is no indication
      for treating the paraaortal lymphatics in patients with locoregional advanced
      prostate cancer. Many radiotherapists perform the elective radiotherapy of pelvic
      lymphatics when the risk of metastases is above 15 to 20% because retrospective
      data indicate a better outcome. On the other hand, many others don't treat them
      because RTOG 75-06 and 77-06 didn't demonstrate a better outcome. Laparoscopic
      lymphadenectomy with low morbidity seems to be helpful as in pN0 patients
      radiotherapy is not necessary. Where performing laparoscopic pelvine
      lymphadenectomy is impossible the probability of the frequency of lymph node
      metastases can be estimated using the clinical tumor stage, the Gleason-score and
      the pretherapeutic PSA. In case of proven metastases (pN+) some retrospective
      data indicate that patients with micrometastasis could profit from aggressive
      treatment. In case of proven metastases and extirpation by lymphadenectomy it
      seems that patients with hormonal therapy and radiotherapy have a longer tumor
      free interval. However, there are no data from randomized trials. CONCLUSIONS:
      Every radiotherapist has to make his own decision for radiotherapy of the pelvic
      lymphatics as there is no standard treatment. Two randomised studies are open and
      recruiting patients. These are one study of the ARO, investigating patients with
      histologically proven lymph node metastases and one study of the RTOG (RTOG
      9413), investigating patients with an estimated risk of lymph node metastases >
      15%. In case of radiotherapy of the pelvic lymphatics a dose of 45 Gy for
      suspected metastases and 50.4 Gy for proven metastases is recommended.

PMID- 9614951
TI  - [Consequences of the latest Euratom directive 96/29 ("basic standard") regarding
      radiotherapy].
AB  - AIM: The Council Directive 96/26 will be brought into force by the Member States
      of the EC until the year 2000. What practical consequences on both mounting and
      holding radiotherapeutical facilities should be considered? METHODS: Regarding
      the Council Directive, facts on workers' actual occupational exposure in medicine
      and representative calculations on structural shielding the consequences will be
      evaluated. RESULTS: Increasing both total number of occupationally exposed
      workers and number of Category A workers but also enforced structural shielding
      should be expected. Working in any protected area during pregnancy will be
      strictly prohibited now. CONCLUSIONS: With respect to the generally sufficient
      structural shielding no restrictions for existing radiotherapeutical facilities
      are to be expected. But it is emphasized to carry out further mountings on base
      of the latest Council Directive 96/26 Euratom.

PMID- 9614952
TI  - [Radiotherapy for painful degenerative joint disorders. Indications, technique
      and clinical results].
AB  - BACKGROUND: Radiotherapy of degenerative joint disorders is almost replaced by
      other treatments, although its efficacy is well known. Compared to orthopedic
      studies radiotherapy data are lacking long-term analysis and objective
      reproducible evaluation criteria. PATIENTS AND METHODS: From 1984 to 1994, 85
      patients with painful osteoarthritis were treated. The mean follow-up was 4 (1 to
      10) years. Seventy-three patients (103 joints) were available for long-term
      analysis: 17 patients (27 joints) with omarthrosis, 19 (20 joints) with
      rhizarthrosis, 31 (49 joints) with osteoarthritis of the knee and 6 patients (7
      joints) with osteoarthritis of the hip. All patients were intensively pretreated
      over long time. Mean symptom duration prior to radiotherapy was 4 (1 to 10)
      years. Orthovoltage or linac photons were applied using some technical
      modifications depending upon the joint. Two radiotherapy series (6 x 1 Gy, total
      dose: 12 Gy, 3 weekly fractions) were prescribed. The interval between the 2
      series was 6 weeks. The subjective pain profile was assessed prior to and 6
      months after radiotherapy and at last follow-up. The classification and
      assessment of pain symptoms were performed using the Pannewitz score and 5 pain
      categories and 3 pain grades. Joint edema and effusion were objective response
      parameters together with special orthopedic scores for each joint. RESULTS: Forty
      six (63%) patients (64 joints) achieved a reduction of pain symptoms; 16 of those
      had a "major pain relief" and 14 "complete pain relief". Large joints--knee and
      hip--responded better (64% each) than the rhizarthrosis (53%). All pain
      categories and grades and their combined pain score were significantly reduced.
      The pain reduction was mostly pronounced for the symptom "pain at rest". The
      orthopedic score correlated well with the subjective response of the patients.
      The thumb score improved in 11 (57%) joints, the shoulder score of Constant and
      Murley [5] in 16 (59%), the Japonese knee score of Sasaki et al. [37] in 33
      (67%), the hip score of Harris [12] in 5 (71%) joints. Only 9 of 19 patients
      which were treated to avoid surgery, had to be operated, and 3 of those received
      a total arthroplasty of the hip or knee. In multivariate analysis for the
      endpoint "complete" or "major pain relief" only the criterion "symptom duration >
      or = 2 years prior to radiotherapy" was an independent negative prognostic
      parameter (p < 0.05). CONCLUSIONS: Radiotherapy for refractory osteoarthritis is
      a very effective treatment option for pain reduction compared to other
      conventional methods. Due to the very low risk of side effects and the low costs,
      radiotherapy provides an excellent alternative to conventional conservative
      treatment methods and in case of inoperability.

PMID- 9614953
TI  - [Cosmetic results of breast conserving therapy for breast carcinoma. Treatment
      results from the Heidelberg Radiation Clinic in the years 1984 to 1992].
AB  - PURPOSE: In this study we retrospectively analyzed local control, survival rate
      and late cosmetic results of women with early breast cancer receiving breast
      conserving therapy. PATIENTS AND METHODS: All patients (1984 through 1992) of the
      Department of Radio-Oncology (University of Heidelberg), who received breast
      conserving therapy consisting of conservative surgery followed by radiotherapy,
      were interviewed and asked to come. Subjective estimation of the cosmetic results
      of therapy was evaluated by means of a questionnaire. Cosmesis, circumferences
      and temperatures of different mammary regions were assessed and measured. Side
      effects and late sequelae were valued by the EORTC/RTOG-score. RESULTS: Mean
      follow-up time of 192 women (pT1: 71.9%, pT2: 28.1%) was 4.5 years (median: 4.0
      years). 26.6% of them were nodal positive. Positive nodal status correlated with
      high tumor grading (p = 0.0001). Ten patients developed distant metastases; one
      of them subsequent to having suffered a loco-regional failure. Eight loco
      regional failures occurred, 3 of them before radiotherapy (salvage). Following
      radiotherapy altogether 5 loco-regional failures (= 2.6%) were found; 3 women
      concerning were pre-, 2 postmenopausal. Three of these patients died, in 1 case
      occurred distant metastasis. Seventeen patients died, 3 of them presenting loco
      regional failure, 8 of them showing distant metastasis. Sixty-four women were
      examined for cosmesis with the following result: a poor result was observed
      twice, a fair result 13 times, a good result 34 and an excellent result 15 times.
      Self-assessment was significantly better than observer's assessment. Third-degree
      late sequelae were found once, second-degree was seen 11 times, first-degree 38
      times and no visible late sequelae were observed 14 times. The use of wedges was
      followed with borderline significance (p = 0.06) either by a better cosmesis and
      fewer late sequelae. Neither the type of surgery nor the width of the fields nor
      the quality of radiation (Co60 or 6 MVX) nor boost-application influenced the
      cosmetic result. Measured circumferences and distances showed no significant
      differences in the groups of the patients with poor or fair and good or excellent
      cosmesis. The temperature of the seized and contralateral breast showed no
      significant difference as well. With increasing distance from primary therapy the
      cosmetic results deteriorated. CONCLUSION: Breast conserving therapy consisting
      of conservative surgery followed by radiotherapy causes predominantly excellent
      to good cosmetic results combined with an acceptable amount of late side effects.
      The decreased rate of good and excellent cosmetic long-term results is biological
      interesting and requires further studies.

PMID- 9614954
TI  - Acute radiation reaction and local control in breast cancer patients treated with
      postmastectomy radiotherapy.
AB  - BACKGROUND: We have investigated the variation of acute radiation reactions in
      medium-risk patients with postmastectomy radiotherapy with regard to a possible
      correlation between radiation reaction of normal tissues and local tumor control.
      MATERIAL AND METHODS: From 1985 through 1991, a total number of 194 patients
      received postmastectomy radiotherapy for breast cancer pT1-2pN0-2M0 at the
      University of Halle-Wittenberg. The lymphatics were irradiated by an anterior 9
      MV photon field and the chest wall by an individually shaped anterior field with
      9-MV electrons. Both fields received single doses of 2 Gy 5 times weekly up to a
      total dose of 44 Gy to the chest wall and 50 Gy to the lymphatics. All patients
      were routinely evaluated once weekly during radiotherapy for acute side effects
      by one examiner. Skin erythema was classified as mild, moderate or severe,
      esophagitis as being present in form of dysphagia or not and pneumonitis, if
      present, as asymptomatic (visible only on repeated chest X-rays) or clinically
      symptomatic. A differential blood count was also carried out once weekly. For
      this analysis, the records of all patients were retrospectively reviewed. The
      median follow-up at the time of analysis was 4.2 years. RESULTS: Of the patients,
      98 (51%) had a mild, 53 (27%) moderate and 43 (22%) a severe erythema.
      Furthermore, 38 patients (20%) had signs of esophagitis, 13 (7%) had asymptomatic
      and 26 (13%) symptomatic pneumonitis. Patients with severe erythema or erythema
      plus esophagitis and pneumonitis had a more pronounced decrease in lymphocyte
      count during treatment than patients with mild erythema: the lymphocyte nadir was
      0.14 vs 0.73 Gpt/l in patients with severe vs mild erythema, and 0.36 vs 0.69
      Gpt/l in patients with erythema plus esophagitis plus pneumonitis vs patients
      with erythema only, p < 0.05. Of the patients, 44 (22%) developed chronic side
      effects, mostly arm edema. There was no correlation between acute and late
      effects. An overall number of seven local recurrences (3.6%) occurred. The risk
      of developing a local recurrence within 5 years after treatment was 0% in
      patients with severe erythema or erythema plus esophagitis/pneumonitis vs 7% in
      patients with mild erythema only; this difference was marginally significant, p =
      0.055. CONCLUSIONS: This analysis showed a trend towards better local control in
      patients with severe acute radiation reaction of normal tissue. The data support
      a recent publication by Dahl and coworkers showing a linkage between acute
      radiation reaction of normal tissue and tumor response in patients with
      preoperative radiotherapy for rectal cancer. The correlation between acute normal
      tissue reaction and local control might be explained by interindividual
      variations in the intrinsic, genetically determined radiosensitivity. However,
      local factors might also be involved, e.g. induction of a cytokin cascade in
      cases of acute reactions in normal tissues.

PMID- 9614955
TI  - The sensitivity of the in vitro cytokinesis-blocked micronucleus assay in
      lymphocytes for different and combined radiation qualities.
AB  - PURPOSE: The dose-response relationship and the relative biological effectiveness
      (RBE) for the induction of micronuclei in lymphocytes was analyzed after
      irradiation in vitro with a 6-MeV neutron beam that was followed by 240-kV X
      rays. The dose range of the combined exposure comprised 1 to 3 Gy. For reference,
      the dose-effect relationships found after X-ray (0.5 to 5 Gy)- and neutron (0.5
      to 4 Gy) exposure applied separately are presented. The possibility of an
      interaction between the 2 radiation qualities is investigated by the method of
      isobole calculation termed "envelope of additivity". METHODS: Micronuclei were
      analyzed in PHA-stimulated, cytokinesis-blocked human lymphocytes. RESULTS: The
      dose-response relationships for the micronucleus frequencies induced by the
      neutron irradiation, as well as by the mixed exposure, were linear. A saturation
      effect was indicated after neutron doses higher than 3 Gy. After low LET exposure
      the dose-response curves were describable by a linear-quadratic model. For
      neutron-induced micronucleus frequencies, RBE-values of 2 to 3 and for the
      combined exposure RBE values of 1.5 to 2 were calculated for a range of effect of
      0.5 to 1.5 micronuclei/binucleated lymphocyte. No indication was found for an
      interaction between the damage induced by X-rays and that produced by neutrons
      under our experimental conditions. CONCLUSIONS: These studies demonstrate a clear
      dependence of micronucleus induction on radiation quality and emphasize the
      usefulness of the micronucleus assay in biological dosimetry, also in cases in
      which high LET radiation or a mixed beam is involved as the radiation source.

PMID- 9614956
TI  - [Optimization of photon dose distributions with compensation].
AB  - PURPOSE: A homogeneous dose distribution according to the demands of the ICRU
      publication 50 often can only be achieved by the use of compensators. Because of
      the expense those are seldom applied. The purpose of this work is to find
      practical methods for the production and verification. MATERIAL AND METHODS: Two
      procedures for the production of compensators using 3 different materials and
      suitable dose verification methods were investigated. The first procedure uses a
      laser system to get the patient contour, from which the compensator can be
      calculated. In a second method a 3D planning system calculates the dose
      modulators on the basis of CT-slices. The production is done by the use of a
      computer driven milling machine either via a founding form or direct milling.
      Mixtures of a polymer and lead powder, a mixture of tin granules and wax and the
      commercially available alloy MCP-96 were used. Dose verification was done using
      film-, TL- and the three-dimensional MR Fricke gel dosimetry as well as a diode
      array scanner. RESULTS: Though both methods can be used, the CT-based procedure
      proved to be more appropriate. Among the materials the direct milled MCP-96
      compensator is favorable with respect to the handling, mechanical properties and
      inhomogeneous radiation attenuation. The dose verification has been done in an
      Alderson phantom for mantlefield and head-and-neck irradiation techniques. Here
      the dose modulation yielded an improvement of the homogeneity. The dose maxima
      normalized to the dose reference point could be reduced from 127% to 103%
      respectively 122% to 104%. Verifications of compensators for patient treatments
      confirmed the good results from the phantom measurements. CONCLUSION: The
      demonstrated investigations show a practicable way for the clinical application
      of compensators. The necessity for the use of them can be derived from the
      verified decrease of the dose maxima.

PMID- 9614957
TI  - Patterns of relapse and late toxicity after resection and whole-brain
      radiotherapy for solitary brain metastases.
AB  - BACKGROUND: This retrospective analysis was performed in order to evaluate the
      pattern of relapse and the risk of late toxicity for solitary brain metastases
      treated with surgery and whole-brain radiotherapy and to correlate the results
      with those from radiosurgical trials. PATIENTS AND METHODS: From a total of 66
      patients, 52 received 10 x 3 Gy and 10 were treated with 20 x 2 Gy whole-brain
      radiotherapy after resection of their brain metastases. RESULTS: The actuarial
      probability of relapse was 27% and 55% after 1 and 2 year(s), respectively. The
      local relapse rate (at the original site of resected brain metastases) was rather
      high for melanoma, non-breast adenocarcinoma, and squamous-cell carcinoma. No
      local relapse occurred in breast cancer and small-cell carcinoma. Failure
      elsewhere in the brain seemed to be influenced by extracranial disease activity.
      Size of brain metastases and total dose showed no correlation with relapse rate.
      Occurrence of brain relapse was not associated with a reduced survival time,
      because 10/15 patients who developed a relapse received salvage therapy. Of the
      patients, 11 had symptoms of late radiation toxicity (the actuarial probability
      was 42% after 2 years). CONCLUSIONS: Most results of surgical and radiosurgical
      studies are comparable to ours. Several randomized trials investigate surgical
      resection versus radiosurgery, as well as the effects of additional whole-brain
      radiotherapy in order to define the treatment of choice. Some data support the
      adjuvant application of 10 x 3 Gy over 2 weeks as a reasonable compromise when
      local control, toxicity, and treatment time have to be considered.

PMID- 9614958
TI  - [Pelvic wall recurrence of cervix carcinomas. Combined surgical-radio
      chemotherapeutic procedure (CORCT)].
AB  - PURPOSE: The prognosis of patients with pelvic wall recurrences after primary
      therapy of cervical cancer is bad. In selected patients treated exclusively by
      surgery as primary therapy the 5-year survival rate was between 5 and 25%.
      Additionally the combination of operation and radiotherapy (CORT) improved the
      survival so far. We developed a new concept for the treatment of pelvic wall
      recurrences. This concept includes the combination of radical surgery,
      interstitial radiation and chemotheray--CORCT (combined operative- and
      radiochemotherapy). PATIENTS AND METHODS: After radical surgery, interstitial HDR
      (Ir-192) brachytherapy in afterloading technique (2.5 Gy, 2 fractions/day in 5
      days) was performed. Additionally a chemotherapy with cisplatin 25 mg/m2/day in 5
      days and 5-fluorouracil 1000 mg/day in 5 days was applicated. RESULTS: After
      combined operative- and radiotherapy 3 of 3 patients died after treatment within
      8 months (median) because of distant metastases. After additive radiochemotherapy
      3 of 4 patients had no evidence of disease (NED) after a follow-up period of 14
      (12 to 30) months. CONCLUSION: The first treatment results of the new designed
      combined operative- and radiochemotherapy concept (CORCT) led us to expect an
      improvement of the prognosis of patients with recurrences of cervical cancer at
      the pelvic wall.

PMID- 9614959
TI  - [Radiation therapy of chronic pancreatitis. Case report].
AB  - BACKGROUND: Chronic pancreatitis is a severe inflammatory process leading to
      destruction of exocrine tissue, fibrosis and a sometimes fatal pancreatic
      necrosis. Therapeutic options are poor and restricted to an exclusively
      symptomatic treatment. In this situation any additional treatment option is
      welcome. CASE REPORT: The present paper reports the successful irradiation of a
      patient with severe chronic pancreatitis resistant to any pretreatment. Pain
      relief was stated one week after beginning of the irradiation. Total dose was 7
      Gy, applied with opposing ap/pa fields using 8 MV photons. Three years after
      treatment the patient has remained free from symptoms. He has gained 14 kg of
      weight and is working regularly.

PMID- 9614960
TI  - ["Marker" of radioresistance in squamous cell carcinoma of the head and neck: a
      clinicopathologic and immunohistochemical study].

PMID- 9614961
TI  - [Economic analysis of adjuvant interferon-alpha-2-therapy in high risk melanoma
      patients based on results of the ECOG 1684 Study Group].

PMID- 9614962
TI  - [Therapy results of the British ET-1 study for Ewing's sarcoma].

PMID- 9614963
TI  - [No advantage to using the CMF-regimen for node positive, postmenopausal,
      receptor-positive mammary carcinoma with adjuvant tamoxifen therapy].

PMID- 9614964
TI  - Assembly of the monomer unit of bacterial peptidoglycan.
AB  - The biosynthesis of peptidoglycan is a two-stage process. The first stage
      concerns the endocellular assembly of its monomer unit, whereas the second one
      concerns the exocellular polymerization steps. The continued interest for this
      system is due to (i) the emergence of new resistance mechanisms; (ii) the need of
      specific targets in the search for new antibacterials; and (iii) the steady
      progress in the study of the correlation of peptidoglycan metabolism with cell
      growth and division. The various steps of the assembly of the monomer unit will
      be discussed as well as the correlations between the two stages. Finally, the
      flexibility of the pathway will be exemplified in Escherichia coli and
      Staphylococcus aureus.

PMID- 9614965
TI  - Cell wall polymers in Archaea (Archaebacteria).
AB  - The distribution of the various cell wall and cell envelope (S-layer) polymers
      among the main lineages of the domain Archaea (Archaebacteria) and the chemical
      composition and primary structure of polymers forming rigid cell wall sacculi is
      described. Differences between bacteria and archaea in their sensitivity to
      antibiotics which inhibit cell wall synthesis in bacteria are discussed.

PMID- 9614967
TI  - Regulation of transcription of cell division genes in the Escherichia coli dcw
      cluster.
AB  - The Escherichia coli dcw cluster contains cell division genes, such as the
      phylogenetically ubiquitous ftsZ, and genes involved in peptidoglycan synthesis.
      Transcription in the cluster proceeds in the same direction as the progress of
      the replication fork along the chromosome. Regulation is exerted at the
      transcriptional and post-transcriptional levels. The absence of transcriptional
      termination signals may, in principle, allow extension of the transcripts
      initiated at the up-stream promoter (mraZ1p) even to the furthest down-stream
      gene (envA). Complementation tests suggest that they extend into ftsW in the
      central part of the cluster. In addition, the cluster contains other promoters
      individually regulated by cis- and trans-acting signals. Dissociation of the
      expression of the ftsZ gene, located after ftsQ and A near the 3' end of the
      cluster, from its natural regulatory signals leads to an alteration in the
      physiology of cell division. The complexities observed in the regulation of gene
      expression in the cluster may then have an important biological role. Among them,
      LexA-binding SOS boxes have been found at the 5' end of the cluster, preceding
      promoters which direct the expression of ftsI (coding for PBP3, the penicillin
      binding protein involved in septum formation). A gearbox promoter, ftsQ1p, forms
      part of the signals regulating the transcription of ftsQ, A and Z. It is an
      inversely growth-dependent mechanism driven by RNA polymerase containing sigma s,
      the factor involved in the expression of stationary phase-specific genes.
      Although the dcw cluster is conserved to a different extent in a variety of
      bacteria, the regulation of gene expression, the presence or absence of
      individual genes, and even the essentiality of some of them, show variations in
      the phylogenetic scale which may reflect adaptation to specific life cycles.

PMID- 9614966
TI  - The structure and function of Escherichia coli penicillin-binding protein 3.
AB  - Escherichia coli penicillin-binding protein PBP3 is a key element in cell
      septation. It is presumed to catalyse a transpeptidation reaction during
      biosynthesis of the septum peptidoglycan but, in vitro, its enzymatic activity
      has only been demonstrated with thiolester analogues of the natural peptide
      substrate. It has no detectable transglycosylase activity with lipid II as
      substrate. This tripartite protein is constructed of an N-terminal membrane
      anchor-containing module that is essential for cell septation, a non-penicillin
      binding (n-PB) module of unknown function and a C-terminal penicillin-binding
      (PB) module exhibiting all the characteristic motifs of penicilloyl serine
      transferases. The n-PB module, which is required for the folding and stability of
      the PB module, may provide recognition sites for other cell division proteins.
      Initiation of septum formation is not PBP3-dependent but rests on the appearance
      of the FtsZ ring, and is thus penicillin-insensitive. The control of PBP3
      activity during the cell cycle is briefly discussed.

PMID- 9614968
TI  - Control of peptidoglycan synthesis in vancomycin-resistant enterococci: D,D
      peptidases and D,D-carboxypeptidases.
AB  - Resistance to glycopeptide antibiotics in enterococci results from the synthesis
      of peptidoglycan precursors with low affinity for these antibiotics. The
      resistance proteins are encoded on transposons in VanA and VanB type enterococci
      and are involved in regulation, synthesis of new resistant precursors and
      elimination of wild-type sensitive precursors by hydrolysis of D-alanyl-D-alanine
      (D,D-peptidase activity encoded by vanX) and removal of D-alanine from UDP-N
      acetylmuramyl (UDP-MurNAc)-pentapeptide (D,D-carboxypept-idase activity encoded
      by vanY). The substrate specificities of VanX and VanY ensure that essentially
      only precursors with low affinity for glycopeptide antibiotics are available for
      peptidoglycan synthesis in strains induced to resistance.

PMID- 9614970
TI  - The diversity, structure and regulation of beta-lactamases.
AB  - beta-Lactamase production is responsible for the appearance of a large number of
      pathogenic bacterial strains exhibiting a high degree of resistance to beta
      lactam antibiotics. A large number of enzymes have been described with very
      diverse primary structures and catalytic profiles. Nevertheless, all known three
      dimensional structures of active-site serine beta-lactamases exhibit a high
      degree of similarity with apparently equivalent chemical functionalities in the
      same strategic positions. These groups might not, however, play identical roles
      in the various classes of enzymes. Structural data have also been recently
      obtained for the zinc metallo-beta-lactamases, but the detailed catalytic
      mechanisms might also differ widely, depending on the enzyme studied. Similarly,
      the induction of the synthesis of beta-lactamases is now better understood, but
      many questions remain to be answered.

PMID- 9614969
TI  - Resistant penicillin-binding proteins.
AB  - Low-affinity penicillin-binding proteins (PBPs), which participate in the beta
      lactam resistance of several pathogenic bacteria, have different origins. Natural
      transformation and recombination events with DNA acquired from neighbouring
      intrinsically resistant organisms are responsible for the appearance of mosaic
      genes encoding two or three low-affinity PBPs in highly resistant strains of
      transformable microorganisms such as Neisseria and Streptococcus pneumoniae.
      Methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococcal
      strains possess the mecA determinant gene, which probably evolved within the
      Staphylococcus genus from a closely related and physiologically functional gene
      that was modified by point mutations. The expression of mecA is either inducible
      or constitutive. A stable high-level resistant phenotype requires the synthesis
      of a normally constituted peptidoglycan. Enterococci have a natural low
      susceptibility to beta-lactams related to the presence of an intrinsic low
      affinity PBP. Highly resistant enterococcal strains overexpress this PBP and/or
      reduce its affinity.

PMID- 9614971
TI  - Protein secretion in Escherichia coli K-12: dead or alive?
AB  - Escherichia coli K-12 possesses a large number of chromosomal genes that, in
      other Gram-negative bacteria, are involved either in exoprotein secretion or in
      the formation of type IV pili. Some of these E. coli genes have been shown to
      encode proteins when expressed from heterologous promoters. Furthermore, at least
      two of these proteins are functional in heterologous complementation tests, but
      none of the genes examined so far is expressed when E. coli is grown under
      standard laboratory conditions. We propose that transcription of these genes is
      turned off during growth in laboratory medium, that their expression is
      controlled by environmental sensor proteins and that they could play an important
      role in pathogenicity or in the utilization of large polymers.

PMID- 9614972
TI  - X-ray studies of enzymes that interact with penicillins.
AB  - The technique of X-ray diffraction has been successfully applied to enzymes
      associated with peptidoglycan biosynthesis. The technique has taught us a great
      deal about the structures and catalytic mechanisms of penicillin-binding proteins
      and beta-lactamases. An insight into the structural basis for antibiotic
      resistance is given.

PMID- 9614973
TI  - NMR structural studies of glutathione S-transferase.
AB  - The use of nuclear magnetic resonance (NMR) spectroscopy for the structure
      determination of small proteins is now widely recognized; what is less frequently
      reported is the application of NMR techniques for high-resolution studies of
      large proteins (M(r) larger than 30 kD). We demonstrate here how an integrated
      approach, using heteronuclear NMR and X-ray crystallography, can provide useful
      and biologically important information for large protein systems. The dynamic
      features of the human Al-1 glutathione S-transferase and the role of the C
      terminal region are being probed by NMR; in the X-ray crystal structure, the
      electron densities for this region of the protein are uninterpretable.

PMID- 9614974
TI  - The folding process of hen lysozyme: a perspective from the 'new view'.
AB  - How a conformationally disordered polypeptide chain rapidly and efficiently
      achieves its well-defined native structure is still a major question in modern
      structural biology. Although much progress has been made towards rationalizing
      the principles of protein structure and dynamics, the mechanism of the folding
      process and the determinants of the final fold are not yet known in any detail.
      One protein for which folding has been studied in great detail by a combination
      of diverse techniques is hen lysozyme. In this article we review the present
      state of our knowledge of the folding process of this enzyme and focus in
      particular on recent experiments to probe some of its specific features. These
      results are then discussed in the context of the 'new view' of protein folding
      based on energy surfaces and landscapes. It is shown that a schematic energy
      surface for lysozyme folding, which is broadly consistent with our experimental
      data, begins to provide a unified model for protein folding through which
      experimental and theoretical ideas can be brought together.

PMID- 9614975
TI  - Beta-lactamases as models for protein-folding studies.
AB  - This review traces some of the key features of the folding of beta-lactamases and
      their relevance to the way proteins fold in general. Studies on the enzymes have
      highlighted the nature and role of equilibrium and transient condensed states.
      The kinetics of folding are multiphasic, and when monitored by acrylamide
      quenching of the tryptophan fluorescence, an early phase provides evidence for
      the transient accumulation of a nonnative intermediate involving burial of
      tryptophan in a nonpolar environment. Intermediate phases can be understood in
      terms of progressive folding of different parts of the molecule. The later, slow
      phases are associated with proline isomerization in the TEM-1 enzyme and, in its
      P167T mutant form, with isomerization from trans to cis of the E166 T167 peptide
      bond. Coupled with kinetic and X-ray crystallographic studies of the beta
      lactamase from Staphylococcus aureus and its D179Q mutant, it appears that the
      final stage of folding is that of collapse and packing of the omega-loop on to
      the main body of the protein.

PMID- 9614977
TI  - [The use of nitroglycerin in integral treatment of hemorrhage with portal
      hypertension].
AB  - The pressure in portal vein had lowered by 28.2% in 36 patients with hepatic
      cirrhosis and portal hypertension influenced by nitroglycerin, applied in the
      dose 0.43 ml/kg in the course of the day. Under such conditions the central
      hemodynamics indexes did not change substantially, no hepatic functional state
      occurred. Nitroglycerin application in complex of therapy showed its efficacy in
      32 patients.

PMID- 9614976
TI  - [Prophylaxis of purulent-inflammatory complications after surgery on the lungs
      and pleura].

PMID- 9614978
TI  - [Functional results of surgical repair of chronic duodenal insufficiency
      associated with duodenal ulcer].
AB  - The results of 312 patients examination in late follow-up period after conduction
      of the organ preserving intervention, gastric resection and reconstructive
      operation with chronic duodenal insufficiency correction, concurrent with
      duodenal ulcer, its acute complications, postvagotomy and postresection syndrome
      are adduced. An excellent and good result was noted in 70.2% of patients, fair-
      in 23.4%, bad--in 6.4%.

PMID- 9614979
TI  - [The involvement of specific immune reactions in the regulation of acid-forming
      function of the stomach in duodenal ulcers].
AB  - Fifty patients with duodenal ulcer disease were examined. In 17 patients (1
      group) the constantly recurrent course of the disease was noted, in 33 patients
      (2 group) the complications (hemorrhage, perforation, stenosing) have occurred in
      anamnesis. In patients of the first group the acid production rising was
      concomitant with specific somatostatin-dependent cell reactions domination, in
      the second one--pentagastrin-dependent.

PMID- 9614981
TI  - [Choledochotomy and its results].
AB  - Of 21 patient to whom after choledochotomy the external drainage of common bile
      duct was conducted, the suture insufficiency have occurred in 3, 2 patients died.
      After choledochoduodenostomy conduction the suture insufficiency was observed in
      3 of 17 patients, 2 patients died. After papilloshincteroplasty conduction the
      complications were revealed in 5 of 23 patients, 3 patients died. Of 4 patients,
      in whom the twin internal drainage was conducted, 3 died.

PMID- 9614980
TI  - [The use of immunomodulators in the surgical treatment of complicated gastric
      disease].
AB  - While examination of 83 patients it was established that in the presence of
      complicated gastric and duodenal ulcer disease the secondary immune deficiency is
      developing, which deepens after the surgical intervention conduction.
      Tiotriazolin, promoting the immune system state and the blood biochemistry
      indexes normalization, the immune system state and the blood biochemistry indexes
      stimulation, hemopoiesis stimulation, the treatment results improvement, was
      applied for immunomodulation.

PMID- 9614982
TI  - [Analysis of the surgical treatment results in patients with acute pancreatitis].
AB  - The results of treatment of 248 patients with an acute pancreatitis (AP) are
      analyzed. Conservative therapy was effective in 178 of them. Mortality was 0.3%.
      Surgical intervention was done in 64 patients, including 25 with AP, of them 2
      (8%) have died; 27--with destructive AP, after cholecystectomy, drainage of bursa
      omentalis and abdominal cavity 15 (55.5%) died. Pancreatic resection, necrotomy,
      programmed relaparotomy with permanent necrotomy of pancreas and retroperitoneal
      cellular tissue were conducted in 17 patients, 3 (17.6%) died.

PMID- 9614983
TI  - [Progress of immune system indices in the treatment of chronic inflammatory
      diseases of the biliary duct].
AB  - In 105 patients with chronic inflammatory illness of gallbladder and biliary
      ducts the generally-accepted therapy have influenced the IgM and IgG contents in
      serum, the lymphocytes sensibilization to the tissue antigens of gallbladder,
      liver, pancreas, the titre of antibodies to this antigens only. The authors
      insist on necessity of supplementary application of immunomodulating agents in
      the complex of patients treatment, especially if reactive hepatitis or
      pancreatitis is present.

PMID- 9614984
TI  - [Use of intraoperative laparoscopic sonography in the diagnosis of hepato
      pancreatic-duodenal duct diseases].
AB  - Laparoscopic doppler sonography was conducted in 245 patients. Its application
      have permitted to diagnose the diseases of gallbladder, pancreas, liver, common
      bile duct, duodenum, to determine the inflammation form, to substantiate the
      extent and tactics of surgical intervention and to reduce the complications
      frequency.

PMID- 9614985
TI  - [Surgical treatment of postop abdominal hernia in elderly and geriatric
      patients].
AB  - There were 180 patients, ageing from 60 to 86 years, operated on for
      postoperative abdominal hernia. An autoplasty with the hernial defect closure
      without the tissues tension was conducted in 123 (68.3%) patients, including 77-
      using an original method. An original method of the combined hernioplasty using
      polyuretanic implant enclosed in a capsule made of a hiatal sac, was conducted in
      57 (31.7%) patients with giant and recurrent hernia. Two (1.1%) patients died. In
      1-7 years after the autoplasty conduction the hernia recurrence was revealed in 5
      (4.7%), in 1-5 years after the combined hernioplasty--in 1 (2.4%) patient.

PMID- 9614986
TI  - [Immunomodulator sensitivity in patients with peritonitis].
AB  - The indexes of the loading rosetteforming tests were studied up in vitro in 10
      healthy persons and in 12 patients with peritonitis. In the patients the
      hyporeactive type of reactivity and multidirectional reaction on immunomodulators
      was revealed more frequently by comparison with such in a healthy persons. The
      individual option of the immunocorrecting agents is mandatory in patients with an
      acute peritonitis.

PMID- 9614987
TI  - [Treatment of patients with failed sutures in the small intestine].
AB  - The suture insufficiency have occurred in 26 (15%) patients after operative
      treatment of 179 patients with different diseases of small intestine. The main
      methods of treatment of this patients are the surgical procedures, intestinal
      intubation, rational antibioticotherapy, the hemostasis correction for the
      postoperative peritonitis liquidation.

PMID- 9614988
TI  - [Surgical treatment of elderly and geriatric patients with femoral hernia].
AB  - The results were summarized on surgical treatment of 56 patients, ageing 60-85
      years, for femoral hernia using two methods--according to Bassini and original
      one stipulated for femoral ring strengthening using implant made of poliuretane
      in hernial sac tunic fixed without tension to inguinal and public ligaments.
      Recurrence of hernia in the late follow-up period have occurred in 13.6% of
      patients operated on according to Bassini and was never observed after operation
      performed using original method.

PMID- 9614989
TI  - [Small intestine anastomosis formation in patients with peritonitis].

PMID- 9614990
TI  - [Treatment of purulent lesions in patients with diabetes mellitus].

PMID- 9614991
TI  - [Traumatic injuries of the abdominal organs].
AB  - The injuries of abdominal cavity organs are analyzed in 1158 injured persons with
      isolated and concomitant trauma. It is established that the injury frequency of
      parenchymatous organs is two times more then of cavitial.

PMID- 9614992
TI  - [Use of computer tomography and magnetic resonance imaging in the diagnosis of
      unstable shoulder joint].

PMID- 9614993
TI  - [The conceptual model of transplants with axial blood supply mechanisms].
AB  - The vascular pedicle types classification, taking into account the group of
      hemocirculation parameters while the combined complexes of tissues
      transplantation and an amputated segments replantation was elaborated. The
      conceptual model of the transplants with an axial type of nutrition blood supply
      is a theoretical basis for determination of the blood supply mechanisms and the
      tissues revascularization possibilities in a modern reconstructive
      rehabilitational surgery.

PMID- 9614994
TI  - [The use of hypertonic sodium chloride solution in combination with dextran in
      patients with head injuries].
AB  - The hemodynamics indexes were investigated in 22 injured persons with
      craniocerebral trauma immediately after and in 5, 30 and 60 min after the blood
      loss occurrence. Rapid compensation of the main hemodynamic indexes disorders was
      guaranteed by infusion to the patients of hypertonic (10%) sodium chloride
      solution with polyglucin at (1:1) ratio in (6.2 +/- 0.6) ml/kg dose.

PMID- 9614995
TI  - [The prospects of laser correlational spectroscopy in differential diagnosis of
      breast tumors and extreme cases in surgery].
AB  - The application possibility of the biophysical method laser correlational
      spectroscopy (LCS), permitting to obtain the information concerning the
      assortment of lightdispersing particles of different sizes, was studied up
      looking for a new approaches to trustful differential diagnosis of oncological
      diseases. Using the LCS method 57 healthy persons, 83 patients with the mammarial
      gland (MG) tumor, 26 with profuse abdominal bleeding, 32 with polytrauma, 68 in
      comatous state were examined. The histograms of the patients with MG cancer
      differed with such of the patients with benign MG tumor. In the patients with
      bleeding the histograms changes have preceded the arterial pressure, the
      erythrocytes quantity and the hemoglobin level lowering. In severe polytrauma the
      LCS application have permitted to disclose the internal bleeding while concurrent
      injury of sceleton bones. In comatous patients the histograms changes were
      revealed in severe craniocerebral trauma, alcoholic and narcotic intoxication and
      an acute disorder of cerebral blood circulation.

PMID- 9614996
TI  - [Non-specific adaptation reactions in burns and their correction].
AB  - The burn disease influence on the adaptational reactions of the organism was
      studied up in 192 injured persons. The stress-reaction was suggested the most
      unfavorable for the prognosis. The severity of pathological reactions is
      lowering, correlating with the complications occurrence frequency, while
      simultaneous application of conventional methods of treatment with combined
      detoxication and nonmedicinal immunomodulation.

PMID- 9614998
TI  - [The use of the enteric sorbent "Silard P" in comprehensive treatment of diabetic
      foot syndrome].
AB  - The expediency of enterosorption application in complex treatment of the purulent
      necrotic affection of foot in patients with diabetes mellitus was substantiated.
      The results of treatment of 36 patients, in 16 of whom enterosorpent "Silard P"
      was applied and in 20--the generally-accepted complex therapy, were analyzed.

PMID- 9614997
TI  - [The effect of ticlid on the late result after the surgery of the brachiocephalic
      trunk arteries].
AB  - No ischemic insult, myocardial infarction, death due to cardiovascular pathology
      was observed in 138 patients, to whom after the operation on the arteries of
      truncus brachiocephalicus the ticlid was administered. At a comparison group (120
      patients) in 3 the myocardial infarction have occurred (one patient died), in 2-
      an ischemic insult. After the ticlid application the positive late follow-up
      result was noted in 93.1% patients, without it--in 70.5%. The preparation
      compliance is good.

PMID- 9614999
TI  - [The use of atrioplasty in the surgical treatment of mitral valve prolapse
      complicated by the enlargement of left atrium].
AB  - Surgical treatment was conducted in 113 patients with the mitral valve failure,
      complicated by significant enlargement of the left auricle (LA). The simultant
      operation had included the mitral valve prosthesis and the LA reducing plasty
      according to the original method. The additional surgical correction of other
      valves affection was conducted in 44 patients. The hospital lethality have
      constituted 6.2%.

PMID- 9615000
TI  - [The use of bi-directional cava-pulmonary anastomosis in the treatment of severe
      congenital heart defects].
AB  - Two-directional cava-pulmonary anastomosis was done in 35 patients with a inborn
      heart failure, ageing from 10 months to 11 years. In 29 patients the significant
      improvement of their state was noted. The level of arterial blood saturation with
      an oxygen have rised up to (90.1 +/- 2)% at average. Of 7 patients with the
      syndrome of right ventriculus hypoplasia one have died, of 27 patients with the
      single venticular heart-3.

PMID- 9615001
TI  - [The aspects of cellular immunity in patients with diabetes mellitus and diabetic
      foot syndrome and its treatment by enteric sorbent "Silard P"].
AB  - The peculiarities of the cell immunity was studied up in 40 patients with the
      diabetic foot syndrome. The cell immunity indexes changes under the enterosorpent
      "Silard P" influence were analyzed.

PMID- 9615002
TI  - [Morphohistological aspects of tumors and tumor-like changes in the thyroid
      gland].
AB  - The results of the thyroid gland (TG) state investigation in 1027 patients,
      ageing from 14 to 75 years, operated on in 1986-1995 yrs., are adduced. In 60.5%
      of patients the diffuse-nodular goitre was diagnosed, in 9.5%--Hashimoto's
      thyroiditis, in 9.5%--TG cancer, in 2.8%--other pathology. To establish the
      interrelationship of pre-cancer changes and a TG cancer it is necessary to point
      out the concomitant morphologic change beside the main diagnosis, which
      determines the clinical tactics.

PMID- 9615003
TI  - [Clinical-morphological aspects in the diagnosis of microcarcinoma of the thyroid
      gland].
AB  - Retrospective analysis of clinical and morphological diagnosis of papillary
      microcarcinoma (PMC) of the thyroid gland in 202 patients is presented. Frequent
      concurrence of the tumor with different kinds of thyroid pathology, the tendency
      for multifocal spread are noted. The authors have tried to find out a correlation
      between the PMC morphological features and clinical signs.

PMID- 9615004
TI  - [Transplantation of organic culture of adrenal grand cortical substance in the
      treatment of post-adrenalectomy hypocorticoidism].
AB  - The organ culture transplantation of the adrenals cortical substance of a newborn
      piglets was applied while 94 patients treatment to whom total adrenalectomy for
      Itsenko--Cushing disease was done. Significant lowering of the substitutional
      hormonal therapy (steroid preparations) dosage was permitted due to the noted
      improvement of hypocorticism clinical course and an organism hormonal security
      indexes. The clinical effect duration is 6-9 months. The methods physiologically
      substantiated, technically simple, economically advantageous, do not cause the
      side effects.

PMID- 9615005
TI  - [The first experiment in endoscopic surgery of the adrenal gland].
AB  - Laparoscopic adrenalectomy (LA) using transperitoneal lateral access was
      conducted in 56 patients from June 1994 to September 1996 yr. Unilateral adrenal
      gland tumor up to 8 cm in diameter was diagnosed in all the patients. All the
      patients are alive. LA is the method of choice in the patients with syndromes of
      Conn, Cushing, pheochromocytoma up to 8 cm in diameter. The LA conduction is not
      indicated if malignant or large (more than 8 cm in diameter) tumor was revealed.

PMID- 9615006
TI  - [Prognosis of collapse during recipient preoperative care for kidney
      transplantation].

PMID- 9615007
TI  - [Prognostic value of initial ultrastructural changes in squamous cell metaplasia
      of junction cell papilloma of the bladder].
AB  - In 48 patients with a junction cell papilloma, in 65--with a junction cell and in
      20--with nondifferentiated bladder cancer the electron-microscopic studying of
      the squamous cell metaplasia signs was conducted. Great prognostic importance of
      an early and overt signs of squamous cell metaplasia was established.

PMID- 9615008
TI  - [Indications for intestinal ureteroplasty].
AB  - Intestinal ureteroplasty was conducted in 81 patient, ageing from 5 to 62 years
      old. The urodynamics and renal function disorders were caused by existing
      obstructive megaureter--in 41, refluxing megaureter--in 9, hydronephrosis--in 7,
      retroperitoneal fibrosis--in 6, traumatic injury of ureter--in 18.

PMID- 9615010
TI  - [Morphological changes in parietal peritoneum in children with appendicular
      peritonitis].

PMID- 9615009
TI  - [Late complications after surgery of acute appendicitis in children].
AB  - The causes of the late complications of appendicular peritonitis were analyzed in
      48 patients (20 of them were previously operated on in the clinic, 28--in other
      hospitals). The principles of treatment, follow-up results, the complications
      prophylaxis are expounded.

PMID- 9615011
TI  - [Characteristics of peritoneal exudate microflora in children with appendicular
      peritonitis].
AB  - Bacteriological investigation of peritoneal exudate was conducted in 131 children
      with peritonitis. The greatest quantity of pathogenic and conventionally
      pathogenic Escherichias and bacteroids was revealed in March, April and
      September. In summer peritonitis was caused by pathogenic and conventionally
      pathogenic Escherichias in association with enterobacterias, staphylococci and
      other microorganisms.

PMID- 9615012
TI  - [Endoscopic assessment in the treatment of chemical burns of the esophagus in
      children].
AB  - The esopagofibroscopy was conducted in 37 children, hospitalized for the chemical
      burn of esophagus. The substantiation of the treatment tactics in injured persons
      was permitted due to the method applied for the burn extent and stage
      determination.

PMID- 9615013
TI  - [The prognosis of complicated acute abdominal disease in children].
AB  - The system of objective estimation of children severity state before and after an
      urgent operations conduction for the acute disease of abdominal cavity and
      retroperitoneal space. Three types of the disease course were delineated on the
      basis of 200 patients, ageing from 3 months to 15 years, examination. While
      stable course the conservative therapy conduction is indicated, while instable-
      the intensive therapy, incorporating the extrarenal depuration methods, and the
      operations when indicated; while the progressing, testifying the incomplete
      sanation of abdominal cavity--the relaparotomy and intensive therapy.

PMID- 9615014
TI  - [Immune reaction to the heterologic test-antigen in mice with anti-cancer
      vaccine].
AB  - The stimulated influence of the antitumoral vaccine, prepared with the help of
      filtrate of the Bacillus mesentericus AB-56 or the antibiotic, extracted from it,
      on the immune answer to heterologic test-antigen (ram erythrocytes) was
      established. While the vaccine injection to laboratory animals with developing
      tumor their capacity to resist to the tumors was rising up.

PMID- 9615015
TI  - [The effect of ethonium-modified bio-fibril surgical threads on the metabolism in
      the kidneys of white rats].
AB  - In experiment on white rats it was established that after the catgut application
      the RNA concentration and the RNA/DNA levels ratio are reducing in the renal
      tissues. This indexes in the sutured tissues have increased more while the
      biofibril, modified with ethonium, application than using other suture materials.

PMID- 9615016
TI  - [Treatment of destructive acute pancreatitis with the new biologically active
      substance in experiments].
AB  - An acute destructive pancreatitis (ADP) was simulated according to the original
      method with subsequent conduction of the conventional conservative therapy and
      pancreatic resection in 25 mongrel dogs. The mortality due to ADP lessening was
      promoted by the new biologically-active substance application.

PMID- 9615017
TI  - [Diagnosis and principles in the treatment of biliary tract lesions in
      laparoscopic cholecystectomy].

PMID- 9615018
TI  - [Morphological and metabolic changes in tissues during surgical suture
      implantation].

PMID- 9615019
TI  - [Mechanisms and methodology of continuous transplantation tolerance].

PMID- 9615020
TI  - [The use of hemodynamic dextran-based plasma substitutes in blood transfusion].

PMID- 9615021
TI  - [Acute obturating colonic ileus of tumoral origin: surgical methodology].

PMID- 9615022
TI  - [Endogenous toxicity in surgery: modern issues in biology and medicine. Part II.
      Diagnosis].

PMID- 9615024
TI  - [Rare complication of chronic pleurisy].

PMID- 9615025
TI  - [The use of endovascular blood irradiation by helium-neon laser for the integral
      prophylaxis of sepsis in kidney allotransplant recipients].

PMID- 9615023
TI  - [Rare pulmonary artery thromboembolism in a patient with type A hemophilia].

PMID- 9615026
TI  - [Differential diagnosis of nodular lesions of the thyroid gland].

PMID- 9615027
TI  - [The treatment of paravesicular infiltrates in acute destructive cholecystitis
      with calculi].

PMID- 9615028
TI  - [The use of hemosorption with DNA-containing GUDS sorbent for intensive therapy
      of endogenous toxicity syndrome in surgical patients].

PMID- 9615029
TI  - [Hemorrhage in the duodenal stump mucosa erosion site after gastric ulcer
      resection with profuse bleeding at its peak].

PMID- 9615030
TI  - [Foreign bodies in the bladder].

PMID- 9615031
TI  - [Use of intraluminal electrophysical methods in the assessment of upper urinary
      tract urodynamics in patients with renal calculi].

PMID- 9615032
TI  - [The effectiveness of contemporary integral treatment of scrotal injuries].

PMID- 9615033
TI  - [Penile fractures].

PMID- 9615034
TI  - [Massive injuries of the abdominal organs in thoracic-abdominal stab wounds].

PMID- 9615035
TI  - [The use of diagnostic knee joint arthroscopy].

PMID- 9615037
TI  - [Postoperative complications in patients with a perforated gastroduodenal ulcer].
AB  - The results of treatment of 538 patients, operated on for perforative ulcer (PU),
      are studied up. Perforative aperture was sutured in 75 patients, in 153 the ulcer
      was excised, in 291 the excision was supplemented by vagotomy, resectional
      methods were applied in 19. In 94 (17.5%) of patients 114 complications have
      occurred after the operation. Postoperative complications were divided into those
      from the wound, in the abdominal cavity organs and retroperitoneal space, from
      the abdominal cavity, respiratory and cardiovascular system. After the operation
      37 (6.9%) of patients have died. Complications and mortality were observed more
      frequently in the patients to whom the perforative aperture suturing and the
      ulcer excision with truncal or selective vagotomy were conducted in the presence
      of the increased operative risk (the elderly and senile age, concurrent diseases,
      widespread peritonitis). The least frequency of postoperative complications and
      mortality were noted after the PU and the ulcer substratum excision supplemented
      by selective proximal vagotomy.

PMID- 9615036
TI  - [45 years of surgical services in the Rovno regional hospital].

PMID- 9615038
TI  - [The importance of the prognosis of a recurrence in choosing the treatment
      procedure in gastroduodenal hemorrhage of peptic origin].
AB  - The results of treatment of 840 patients with ulcer bleeding are adduced. The
      bleeding recurrence is noted in 88 (10.5%) patients. The monofactorial analysis
      conduction have established 14 trustful prognostical criteria, on the basis of
      which the prognostic index is proposed with 76.1% sensitivity and 73.2%
      specificity. As a result the indications for the surgical treatment of patients
      with high operational risk and with low risk of the bleeding recurrence were
      restricted. In 1996 yr. the bleeding recurrence frequency was 6%, operational
      activity--19.1%, total mortality--2.3%, postoperative mortality--5.1%.

PMID- 9615039
TI  - [The effect of a DC electrical field on pancreatic function in acute
      pancreatitis].

PMID- 9615040
TI  - [The function of the thiol-disulfide and ascorbate systems in patients operated
      on for acute pancreatitis after the use of low-intensity infrared laser radiation
      and pentoxifylline].
AB  - In patients with an acute destructive pancreatitis the lowering of sulphhydride
      (SH) groups in proteinic and nonproteinic fraction of the blood plasma, the
      reduction of the ascorbic acid level and increase of its oxidized forms
      concentration was noted. After the operation the disordered indexes have
      restored, moreover, and after the programmed relaparotomy conduction--as after a
      single operative intervention. Acceleration of the disordered indexes restoration
      was promoted by application of pentoxifylline and low-intensity laser irradiation
      as well.

PMID- 9615041
TI  - [The use of preoperative percutaneous transhepatic cholecystostomy in obstructive
      jaundice].
AB  - In 133 patients with obturating jaundice the conventional treatment was applied
      (group I), in 36 patients as a first phase of surgical treatment the
      transcutaneous transhepatic cholecystectomy was conducted (group II). The
      postoperative complications frequency have constituted 37.3 and 30.5%, mortality-
      27.8 and 13.9% accordingly.

PMID- 9615042
TI  - [The comprehensive prevention of suppurative wound infection in the postoperative
      period in diabetic patients].
AB  - The strict acceptance of the radicalism principles while the purulent
      inflammation origin eliminate, an accurate sanation and early placement of suture
      on the operation wound, its adequate and active drainage in combination with
      expedient local with the help of foamy aerosol "Dioxizol" and stable compensation
      of hyperglycemia, correction of the homeostasis disorders are necessary in the
      treatment of diabetes mellitus patients with local purulent-necrotic disease of
      the soft tissues.

PMID- 9615043
TI  - [Disorders of the blood microcirculation in patients with suppurative-necrotic
      complications in diabetes mellitus and the approaches to their correction].
AB  - The results of surgical treatment of 153 patients with diabetes mellitus,
      suffering from purulent-necrotic complications, were analyzed. The inclusion of
      parmidin and trental in the complex of treatment have promoted their
      convalescence and the improvement of microhemocirculation and immunological
      indexes.

PMID- 9615044
TI  - [The prognosis of the immediate and late sequelae of mild closed craniocerebral
      trauma].
AB  - Were examined 310 injured persons with the closed cranio-cerebral trauma. Follow
      up is up to 25 years. Various psychoneurological and vegetovisceral disorders are
      revealed. The recommendations for the patients treatment are given.

PMID- 9615045
TI  - [Combined intensive therapy and anesthesiological support for a surgical
      intervention in patients with necrotic pancreatitis].
AB  - The results of surgical treatment of 93 patients with necrotic pancreatitis are
      adduced. Of 71 patients, operated on using laparotomy, 18 (25.3%) have died, of
      22 patients, in whom the laparoscopy (LS) was used, 1 (4.5%) have died. In 17
      patients the laparotomy was omitted due to combination of LS with complex
      conservative treatment. Of 44 patients operated on 3 (6.8%) have died during the
      period of the improved tactics introduction.

PMID- 9615046
TI  - [The role of a hypertonic sodium chloride solution in eliminating hypovolemia and
      its effect on water-electrolyte balance].
AB  - Inclusion of hypertonic (5%) solution of sodium chloride in polyglucin or
      rheopolyglucin in the infusion-transfusion therapy composition during the
      operation performance for gastrointestinal bleeding have permitted to eliminate
      circulatory nonstability rapidly, to rise the blood osmolarity of the expense of
      the sodium and chlorine concentration rising, to heighten the urination rate at
      the expense of the glomerular filtration increase, and as a result the excretion
      of sodium, chlorine and potassium out of the organism have increased.

PMID- 9615047
TI  - [The use of enterosorption for the correction of endogenous intoxication in the
      acute period of severe craniocerebral trauma].

PMID- 9615048
TI  - [Osteosynthesis in injury to the pelvic girdle].
AB  - The pelvic bones osteosynthesis was conducted in 94 patients. While planning the
      treatment the author have used the pelvic injuries classification of AO. The
      plates, screws, the external fixation apparatus, the method of 8-figure wire
      circlage were used for osteosynthesis. In 6 patients osteosynthesis was conducted
      for stable pelvic fracture (of the iliac bone in young patients), in 48 the
      operation on the anterior half--ring was conducted for the rotationally nonstable
      injury, in 38--for the vertical--nonstable fracture. Osteosynthesis of the
      ventral and dorsal parts of pelvis was conducted in 12 patients. The introduction
      of the stable-functional osteosynthesis methods have permitted to exclude the
      necessity of the additional immobilization application, to achieve good results
      in the majority of patients with pelvic injuries.

PMID- 9615049
TI  - [The occurrence of a urinary fistula after kidney transplantation].
AB  - The experience of 240 renal transplantation operations conduction is summarized.
      Urinary fistula have occurred in 28 (12%) patients. The causes, clinical signs,
      methods of diagnosis and principles of treatment of complication are analyzed.
      The advantages of an active surgical tactics using modern methods, transcutaneous
      punction pyelo- and nephrostomy under the ultrasound examination guidance, in
      particular, are substantiated.

PMID- 9615050
TI  - [Reflux esophagitis and cicatricial stenosis of the muff-like esophageal-small
      intestine anastomosis after performing a gastrectomy for stomach cancer].
AB  - In the late follow-up period after gastrectomy conduction for gastric cancer
      using antireflux muff-like esophago-jejunal anastomosis 587 patients were
      examined. Mild reflux esophagitis was revealed in 29 (4.9%), moderate--in 9
      (1.5%) of patients. Cicatricial stenosis of anastomosis have occurred in 127
      (8.5%) of patients, including an early one--in 70.1% and the late--in 29.9%. The
      dilation using tubular bougies, passed along the guide, proved effective in the
      treatment of early stenosis. The stenosed part was cut through the endoscope with
      subsequent bougienage for the late stenosis.

PMID- 9615051
TI  - [The use of neoadjuvant selective intra-arterial polychemotherapy and its
      modifier verapamil in the combined treatment of colorectal cancer].
AB  - After combined treatment of 74 patients for colorectal cancer using preoperative
      neoadjuvant intraarterial selective polychemotherapy (IAPCT) three-year survival
      index have constituted (77.0 +/- 5.2)%, the cancer recurrence have occurred in
      (10.8 +/- 2.8)%, distant metastases were revealed in (17.5 +/- 4.2)%. Using
      verapamil as a IAPCT modifier in 54 patient three-year survival have increased by
      11.8%, the frequency of distant metastases occurrence have reduced by 10.1%.

PMID- 9615052
TI  - [Reconstructive-plastic operations as one of the measures for the medical
      rehabilitation of lung cancer patients].
AB  - The follow-up result of reconstructive-plastic operations in 68 patients with
      pulmonary cancer are studied. Preoperative irradiation therapy (20 Gr the summary
      dose), using middle fractions, was conducted in 21 patients. While doing the
      operation, pleura was worked by polymethylsiloxane-400 in 32 patients for the
      postoperative adhesive pleuritis prophylaxis. The patients survival index after
      reconstructive-plastic operations did not differ from such in a control group.

PMID- 9615053
TI  - [The diagnosis of malignant pleural mesothelioma].

PMID- 9615054
TI  - [The surgical treatment of patients with skin melanoma of the extremities and
      trunk].
AB  - The surgical method of treatment late follow-up results of 901 patient with body
      and extremities skin melanoma in stages T1-4 N0M0 were analyzed. It was
      established that melanoma is metastasizing into the regional lymphatic nodes. The
      metastases are occurring from 1 month up to 20 years. Only 67.7% of patients
      survive more that three year and 53.5%--5 years after the tumor excision.

PMID- 9615055
TI  - [The antitumor activity of vaccines obtained by using a culture broth filtrate of
      Bac. mesentericus AB-56 or antibiotic AB-56].
AB  - The possibility of the purified antibiotic, extracted from the Bac. mesentericus
      AB-56 culture liquid, application for the antitumoral vaccine preparation and
      standardization was established in experiment, conducted on the mice of Balb/c
      line.

PMID- 9615056
TI  - [Endolymphatic therapy in the treatment of primary delimited melanoblastoma of
      the skin].
AB  - The results of treatment of 1128 patients with the body and extremities skin
      melanoma were analyzed. The increase of five-year survival index in patients with
      the tumor of T1-4 N0M0 stage by 11.4% was promoted by the postoperative adjuvant
      endolymphatic chemotherapy application. The dacarbasin endolymphatic infusion
      together with recombinant interferon laferon have permitted to increase the
      survival index of patients by 15.4%.

PMID- 9615057
TI  - [The dynamic indices of lipid peroxidation and of the antioxidant system under
      the influence of surgical treatment in ovarian cystoma].
AB  - The state of the lipids peroxide oxidation (LPO) and antioxidant system (AOS) was
      studied up in 22 patients with ovarian cystoma [correction of cyst]. According to
      the level of retinoli acetas, acidum ascorbinicum, tocopheroli acetas, the
      reduced glutation superoxiddysmutase (SOD) activity. The LPO activation and
      vitamins level lowering in the patients blood plasma were established. The
      operative intervention conduction caused the LPO activation and the AOS factors
      level lowering, observed during 7-8 days after the operation.

PMID- 9615058
TI  - [The use of computed and magnetic resonance tomography in the diagnosis of
      neoplasms of the pelvic bones and sacrum].
AB  - The experience of the computed tomography (CT) application in the pelvic bones
      and sacrum tumors diagnosis in 46 patients was summarized. The data obtained were
      defined more precisely using magnet-resonance tomography (MRT). MRT in
      contradistinction to permits to differentiate the soft tissues and reveal the
      tumoral invasion of dura mater and the spinal cord substance, the spinal cord
      nerves affection. Using CT it is possible to estimate more accurately the bone
      structure and tumoral elements, containing calcium.

PMID- 9615059
TI  - [The effect of trental and thiotriazoline on tissue blood flow, oxygen tension
      and vascular reactivity in the pancreas in acute experimental pancreatitis].
AB  - It was established while experiments on dogs that in an acute pancreatitis the
      vessels reactivity is changing, the tissue blood flow and oxygen pressure (pO2)
      are lowering in pancreatic tissue. Infusion of trental and thiotriazolinum didn't
      impede the tissue blood flow lowering but reduced significantly the oxygen
      consumption by pancreatic tissue.

PMID- 9615060
TI  - [Endogenous intoxication in surgery: the current aspects of biology and medicine.
      III. Treatment].

PMID- 9615061
TI  - [Prognostication of the course of early postoperative period after radical
      correction of tetralogy of Fallot].

PMID- 9615062
TI  - [Indications for and prognostication of results of lumbar sympathectomy in
      patients with obliterating atherosclerosis of the lower limbs with chronic
      critical ischemia].
AB  - The instrumental methods of investigation data, permitting to estimate the
      regional hemodynamics state in affected extremity, was used for the lumbar
      sympathectomy (LS) result prognosis in patients with obliterating atherosclerosis
      of the lower extremities vessels while chronic critical ischemia. The LS
      conduction is indicated in patients with critical ischemia in the stage of the
      regional blood flow compensation if it is impossible to conduct the restorative
      operation.

PMID- 9615063
TI  - [Classification and formulation of clinical diagnosis in peptic ulcer].
AB  - An ulcer disease classification, basing on the disease clinical course criteria
      and the local changes characteristics, is proposed. An adequate estimation of the
      patient state and optimal tactics of treatment are guaranteed by the diagnosis
      formulation using the classification.

PMID- 9615064
TI  - [Intestinal decompression and correction of enteral insufficiency in
      postoperative peritonitis].

PMID- 9615065
TI  - [Clinico-endoscopic and pathophysiological correlations in acute appendicitis].

PMID- 9615066
TI  - [Complex prevention and treatment of postoperative suppurative-septic
      complications using constant-current electric field].

PMID- 9615067
TI  - [Surgical treatment of perforated gastroduodenal ulcer].
AB  - The surgical treatment tactics of patients with perforative gastroduodenal ulcer
      was substantiated, basing on the complex analysis done. Radical intervention,
      mainly organ preserving one, constitutes the operation.

PMID- 9615068
TI  - [Dynamics of morbidity of acute appendicitis].

PMID- 9615070
TI  - [Effects of primary focus of malignant cutaneous melanoblastoma on the outcome of
      surgical treatment of regional lymphogenic metastases].
AB  - The indexes of the disease remission dynamics proved to be les favourable in
      patients with lymphogenic metastases revealed while the first visit to oncologist
      (stage T1-4N1M0) in comparison with those, in whom the metastases in regional
      lymph nodes have appeared after the primarily restricted cutaneous melanoma T1
      4N1M0 excision. The survival indexes of the patients were similar.

PMID- 9615069
TI  - [Changes in lipid metabolism and indicators of immunological reactivity in
      programmed relaparotomy in acute pancreatitis].
AB  - The increase of low-density lipoproteids contents, high-density lipoproteids
      level lowering, reduction of the lymphocytes blast transformation reaction
      indexes, IgG level lowering, the rosette formation reduction were noted in
      patients with an acute pancreatitis. While the programmed relaparotomy
      application of the lipid-aliphatic metabolism restoration was noted, and the
      immunological reactivity as well with the dynamics higher than after single
      operative intervention conduction.

PMID- 9615071
TI  - [Use of CT and magnetic resonance tomography in the differential diagnosis of
      nontumorous diseases simulating presence of neoplasms in the pelvic cavity].
AB  - Using X-ray computer tomography and magnet-resonance tomography 656 patients with
      various volumetric formation in pelvic cavity were examined. In 14 (2.1%) of
      patients nontumoral disease, simulating the neoplasm presence in a small pelvis
      cavity, was revealed.

PMID- 9615072
TI  - [Immediate and early results of combined treatment of colonic cancer using
      neoadjuvant selective intra-arterial polychemotherapy].
AB  - The combined treatment of 53 patients with colonic cancer, using neoadjuvant
      intraarterial polychemotherapy (IAPCT), was conducted. The trustworthy lowering
      of the catheterized artery thrombosis occurrence rate, the tumor recurrence-by
      7%, distant metastases-by 13.9%, two-year survival increase-by 15.5% was promoted
      by verapamil application as a IAPCT modifier.

PMID- 9615074
TI  - [Effects of dopamine administered at the time of cadaver donor conditioning on
      the course of acute postischemic insufficiency of the renal allotransplant].
AB  - The various doses of dopamine efficacy, applied for the inotropic support in 30
      donors of kidneys, was investigated, as well as the preparation influence on the
      renal transplantation function. Inotropic support of donor using dopamine was
      needed in 21 donors. The occurrence rate of an acute necrosis of tubules have
      depended upon dopamine doses. Dopamine is the preparation of choice for the
      intensive therapy conduction and securing of cardiovascular stability of the
      donors kidneys.

PMID- 9615073
TI  - [Use of adjuvant therapy in patients with metastasis of melanoma to regional
      lymph nodes].
AB  - The results of treatment of 276 patients with cutaneous melanoma of T1-4N1M0
      stage were analyzed. The irradiation therapy conduction did not influence the
      result of surgical treatment. The trustworthy improvement of three-year survival
      index of patients after the radical operation conduction was noted under the
      influence of the endolymphatic cytostatic therapy. The result of preoperative
      endolymphatic chemotherapy and interferon therapy conduction is quite similar.

PMID- 9615075
TI  - [Clinical symptoms of biocompatibility of dialysis membranes].

PMID- 9615076
TI  - [Use of enterosorption in correction of immune changes during the acute period of
      mild craniocerebral trauma].
AB  - The immune system indexes were studied in 30 injured persons with craniocerebral
      trauma. In 15 patients (1st group) the conventional methods of treatment were
      applied and in 15 (2nd group)--the enterosorption using polysorb MP was included
      in the complex of treatment. Rapid regression of neurological symptoms was
      promoted by the enterosorption application.

PMID- 9615077
TI  - [Post-traumatic hydrocephalus].

PMID- 9615078
TI  - [Causes of disorders of vitally significant functions in surgical treatment of
      extracerebral parastem tumors of the posterior cranial fossa].
AB  - The postoperative period course and an autopsy data of 68 patients operated on
      for n. vestibulocochlearis neurinoma, parasternal meningioma, cholesteatoma.
      Principal damaging factors and cerebral stem functional disorders are assigned.

PMID- 9615079
TI  - [Restoration of flexion of the elbow joint in patients with old injuries of the
      brachial plexus].
AB  - Examination of 23 patients with complete disorder of the flexion function due to
      irreversible injury of plexus brachialis. The translocation of m. triceps brachii
      in 8 patients, m. latissimus dorsi--in 8, m. sternocleidomastoideus--in 5, m.
      pectoralis major transposition was conducted in 1-5 years after the injury for
      the m. biceps brachii function substitution. The most complete restoration of
      flexion in articulation ulnaris was achieved after m. latissimus dorsi
      transposition. Good result was achieved after m. triceps brachii transposition
      conduction.

PMID- 9615080
TI  - [Adaptation reserves in women operated on for tubo-peritoneal infertility].

PMID- 9615081
TI  - [Experimental substantiation of extragastric vagotomy in the surgical treatment
      of gastric and duodenal ulcer].
AB  - The small intestine vagotomy influence on gastric secretion function, stimulated
      by pentagastrin and carbachol, was investigated while chronic experiment on dogs
      with gastric fundal and duodenal fistulas. The comparative analysis of influence
      of extragastric selective proximal, selective distal, selective and truncal
      vagotomy on gastric secretion in various terms after operative intervention was
      also conducted. In 6 months after conduction of various kinds of vagotomy the
      reduction of hydrochloric acid secretion, stimulated by pentagastrin, was noted.

PMID- 9615082
TI  - [Effects of constant-current electric field on tissue and plasma proteolysis in
      acute pancreatitis].
AB  - The tissue and plasma proteolysis changes were studied up on white laboratory
      rats while the pancreas zone galvanization using electrical field of 0.01-0.05
      0.10 mA/cm2 density during 60 minutes. It was established that intratissue
      electrophoresis with contrykal lowers the low molecular mass peptides lysis by
      6.6 times, the high molecular mass peptides-by 4.4, collagen-by 3.

PMID- 9615083
TI  - [Current trends in quality assurance in surgery].

PMID- 9615084
TI  - [Prevention of postoperative deep vein thrombosis of the lower limbs].

PMID- 9615085
TI  - [Diagnosis and surgical treatment of organic hyperinsulinism].

PMID- 9615086
TI  - [Performance of organ-preserving surgery in breast cancer].

PMID- 9615087
TI  - [Problems of postgraduate education during internship].

PMID- 9615088
TI  - [Method of surgical treatment of postoperative abdominal hernia].

PMID- 9615089
TI  - [Surgery of cardiac myxoma of rare localization].

PMID- 9615090
TI  - [Immune correction of healing of intestinal anastomosis].

PMID- 9615091
TI  - [Thromboembolic and hemorrhagic complications after appendectomy].

PMID- 9615092
TI  - [Immediate results of surgical treatment of patients with incarcerated recurrent
      giant hernia].

PMID- 9615093
TI  - [Etiology of postoperative abdominal hernia].

PMID- 9615094
TI  - [Restoration of reproductive ability in patients with chronic prostatitis].

PMID- 9615095
TI  - [Immediate and late results of open and transurethral adenomectomy].

PMID- 9615096
TI  - [Volvulus of the ileocecal junction in colonic dystopia].

PMID- 9615097
TI  - [Content of middle molecular mass peptides in the blood of patients with ovarian
      tumor at the time of surgical treatment].

PMID- 9615098
TI  - [Respiratory tract foreign bodies in children].

PMID- 9615099
TI  - [Performance of duplicature surgery of the anteromedial zone of the knee joint
      for its stabilization].

PMID- 9615101
TI  - Swiss Academy of Medical Sciences. Annual Report 1996.

PMID- 9615100
TI  - Vth International Conference. Current Trends in Chronically Evolving Viral
      Hepatitis. Lyon, France, October 10-11, 1997. Abstracts.

PMID- 9615102
TI  - [Stress proteins].

PMID- 9615103
TI  - [Combination of dacarbazine, cisplatin and interferon alpha in the treatment of
      metastatic melanoma].
AB  - INTRODUCTION: The aim of this work was to study the effectiveness and safety of a
      combined therapy with dacarbazine, cisplatin and interferon alpha in the
      treatment of metastatic melanoma. PATIENTS AND METHODS: Sixteen patients,
      including 15 with one or more visceral metastases, were treated with dacarbazin
      400 mg/m2, cisplatin 100 mg/m2 repeated every 28-day and interferon alpha-2a
      3.10(6) IU subcutaneously 3 times weekly. Fifty percent of patients had at least
      3 different sites of metastases. Ten patients had previously received one or more
      specific treatment for their melanoma. RESULTS: The overall response was 25 p.
      100 (2 complete responses and 2 partial responses). The two complete responses
      were obtained on liver, lung and cutaneous metastases and remain in sustained,
      unmaintained remission for 22 and 24 months. Administration of this treatment was
      well tolerated, the most prevalent toxicity being hematologic. At present,
      responding patients have a median survival of 26 months+ since the beginning of
      the treatment, compared to 7 months for non responding patients. DISCUSSION:
      Dacarbazine and cisplatin combined chemotherapy has been used at various doses
      with an overall response rate of 14 to 37 p. 100, similar to our results.
      However, duration of complete response in our study (22 months+ and 24 months+)
      seem more prolonged than in studies using dacarbazine and cisplatin at dose of
      100 mg/m2/21 d (7 to 9 months) and comparable to studies using dacarbazine and
      cisplatin at dose of 150 mg/m2/28 d or more (15 months+ to 19 months+ and 24
      months+) but with less toxicity. Therefore addition of interferon alpha might be
      of interest in the maintain of complete remissions and perhaps in the
      prolongation of survival of responding patients as it has already been suggested
      with the dacarbazine-interferon alpha combination.

PMID- 9615104
TI  - [Bullous IgA linear dermatosis of children in Mali].
AB  - INTRODUCTION: Bullous IgA linear dermatosis is relatively frequent in children in
      Africa. The aim of this study was to evaluate the frequency of this disease among
      autoimmune bullous diseases in children in Mali. PATIENTS AND METHODS: Children
      with chronic bullous disease seen at the Marchoux Institute in Bamako and for
      whom direct immunofluorescence of the perilesional skin demonstrated
      immunoglobulin and/or complement deposits were included in the study population.
      RESULTS: Twelve children were included. Direct immunofluorescence showed linear
      IgA deposit along the dermo-epidermal junction in 10, once with a pemphigoid
      aspect and once with a pemphigus aspect. The skin lesions in the children with
      linear IgA deposits were stereotypic: disseminated bullae, rosettes (9 out of
      10), involving the external genital organs (10/10), the limbs, the face and the
      trunk. Histology showed subepidermal bullae (10/10), with neutrophil papillar
      abscesses (9/10). Indirect immunofluorescence of the cleaved skin NaCl in 5
      patients showed that the cleavage always lied at the roof of the cleavage. All
      the children responded to dapsone (1 to 2.5 mg/kg/d) which gave complete (7/10),
      or incomplete remission. Local corticosteroids were used in 2 patients and
      general corticosteroids in 1. DISCUSSION: This confirms the frequency of bullous
      IgA linear dermatosis in Africa, in contrast with uncommon dermatitis
      herpetiformis. Diagnosis is facilitated with immunofluorescence. The low cost of
      this test makes it a useful diagnostic tool in these countries.

PMID- 9615105
TI  - [Perianal papulonodular dermatitis in Hirschsprung disease].
AB  - INTRODUCTION: Macerations resulting from anal and/or urinary incontinence can
      lead to perineal or peristomal pseudo-verrucosis. The papulo-nodular perianal
      lesions observed in children after surgery for Hirschsprung syndrome is an
      example. CASE REPORT: A 28-month-old boy with rectosigmoid Hirschsprung disease
      developed chronic diarrhea after surgery with colo-anal anastomosis followed
      rapidly by perineal rash. The rash did not respond to local treatments and pseudo
      condylomatous papulonodules developed. Infection, deficiency and tumoral causes
      were eliminated. Skin biopsy showed benign epidermal hyperplasia. The lesions
      regressed spontaneously within a few weeks after the diarrhea had been controlled
      and diapers were no longer used, confirming the diagnosis of perianal papulo
      nodular dermatosis following surgical treatment for Hirschprung disease.
      DISCUSSION: The presentation of the perianal rash was similar to Sevestre and
      Jacquet dermatitis and infantile gluteal granuloma. The pathogenesis is similar
      to perianal or peristomal pseudoverrucosis seen in incontinent or stomy patients.
      Diagnosis is based on the clinical presentation, the periorificial localization
      and the pseudo-tumoral aspect of the lesions. Removal of the cause of maceration,
      when possible, is the basis of treatment.

PMID- 9615107
TI  - [Generalized pseudoxanthoma elasticum combined with vitamin K dependent clotting
      factors deficiency].
AB  - INTRODUCTION: Pseudoxanthoma elasticum is a connective tissue disease currently
      classed in 4 forms. Two forms are inherited via dominant autosomal transmission
      and the other two via recessive autosomal transmission. The generalized form of
      pseudoxanthoma elasticum is the most uncommon form and corresponds to recessive
      type II. Clinical manifestations include the typical generalized "peau d'orange"
      skin associated with hyperlaxity of the skin. Usually, there is no systemic
      manifestation. CASE REPORT: We report a case of a patient with generalized
      pseudoxanthoma elasticum associated with deficiency of vitamin-K dependent
      factors II, VII, IX, and X. A search for other causes of vitamin-K dependent
      factor deficiency was negative. DISCUSSION: The association of generalized
      pseudoxanthoma elasticum with deficiency of vitamin-K dependent clotting factors
      has been reported previously in very rare cases and is probably not fortuitous.
      It could led to the definition of a sub-group of recessive autosomal
      pseudoxanthoma elasticum.

PMID- 9615106
TI  - [Pyogenic granuloma of the tongue in chronic graft versus host disease].
AB  - INTRODUCTION: The development of pyogenic granuloma of the tongue is rare. We
      report such a case in a patient with chronic graft-versus-host disease. CASE
      REPORT: A 5-year-old girl was treated with allogenic bone marrow transplantation
      for aplastic anemia. Complications consisted in chronic graft-versus-host disease
      with cutaneous, mucosal and hepatic involvement. Seven months later, a voluminous
      pyogenic granuloma of the tongue developed on previous erosive lichenoid lesions
      of chronic graft-versus-host disease while the patient was under cyclosporin.
      Surgical resection was done. Relapse occurred and treatment was identical.
      DISCUSSION: Six cases of pyogenic granuloma of the oral cavity in chronic graft
      versus-host disease have been reported in the literature. Pyogenic granuloma must
      be considered in tumoral lesion of the oral cavity of patients with chronic graft
      versus-host disease. All patients had erosive lichenoid lesions and were under
      cyclosporin; its role in the genesis of these lesions is debated. Treatment
      relies on surgical resection confirming the diagnosis.

PMID- 9615108
TI  - [Capillary leak syndrome disclosing Ofuji's papuloerythroderma].
AB  - INTRODUCTION: Capillary leak syndrome is a specific entity among syndromes with
      capillary hyperpermeability. Endothelial cell activation is related to the higt
      level of adhesion molecules (sICAM-1, sVCAM-&, sCD62E) possibly due to several
      cytokines (IL-2, TNF ...). CASE REPORT: An 84-year-old woman was hospitalized for
      erythroderma. Ofujui papuloerythroderma was diagnosed and edema was attributed to
      capillary leak. A kinetic study of several cytokines and adhesion molecules
      sCD62E, sVCAM-1 and sICAM-1 was done. Outcome was favorable with
      corticopuvatherapy. DISCUSSION: The capillary leak syndrome reported here is
      simlar to that described in other erythrodermas with or without lymphoma. The
      keratinocyte would be activated by the CD4 T lymphocyte via the gamma-interferon
      mediator. The T cell secretes cytokines (interleukin-1, tumor necrosis factor
      ...) which activates the endothelium and increases vascular permeability. The
      level of adhesion molecules and changes observed during the episode of edema
      demonstrated the endothelial activation.

PMID- 9615109
TI  - [Peusoxanthoma elasticum with multiple calcinosis and hyperphosphoremia].
AB  - INTRODUCTION: Subcutaneous and vascular calcifications are classical
      manifestations of pseudoxanthoma elasticum. Visceral calcifications sometimes
      associated with unbalanced phosphocalcium leels are uncommon. CASE REPORT: We
      observed pseudoxanthoma elasticum in a French Caribbean patient who had extensive
      acneiform skin lesions with transepidermal elimination. Multivisceral
      calcifications were associated hyperphosphoremia alone. DISCUSSION: The
      pathogenic sequence of phosphocalcium disorders in this disease are discussed on
      the basis of calcifications and hyperphosphoremia observed in this case and from
      data in the literature.

PMID- 9615110
TI  - [Waldman's disease. Primary intestinal lymphangiectasis].
AB  - INTRODUCTION: Primary intestinal lymphangiectasias are often associated with
      lymphoedema. OBSERVATION: The diagnosis was performed at 4 months when Maxime
      presented with lymphoedema, diarrhea, hypoprotidemia and hypolipemia. Duodenum
      biopsies revealed intestinal lymphangiectasias. An hyperprotidic and low fat
      diet, medium chain triglyceride-supplemented and an elastic contention allowed a
      decline of the oedemas. DISCUSSION: We report one case of Waldman's disease. It
      shows very well the typical circumstances of diagnosis in this disease and the
      two types of oedema (lymphoedema and hypoprotidic oedema).

PMID- 9615111
TI  - [Eccrine carcinoma with mucinous stroma of the face].
AB  - INTRODUCTION: We report a new case of eccrine carcinoma with mucinous stroma
      characterized by its voluminous exophytic growth. CASE REPORT: An 80-year-old
      patient was hospitalized for a voluminous vegetating tumor localized over the
      left temporal region and which had developed over the 10 preceding years. Wide
      exeresis was performed and histology confirmed the diagnosis of eccrine
      carcinoma. No locoregional recurrence was noted 18 months later. DISCUSSION:
      Eccrine carcinoma with mucinous stroma, also termed eccrine mucinous
      adenocarcinoma, is a rare adnexal skin carcinoma usually localized on the face or
      scalp. Abundant zones of mucine are characteristic dissociating a dermal cell
      proliferation with ruban architecture. The volume of the tumor in our case was
      particularly remarkable although outcome was favorable after surgical treatment.

PMID- 9615112
TI  - [Papular plaque-type blue nevus].
AB  - INTRODUCTION: Rare clinical presentations of common diseases are sometimes worth
      of publication. Their knowledge may help to avoid diagnostic mistakes.
      OBSERVATION: In a 6 year-old boy a cluster of pigmented blue papules spread
      slowly on the inner aspect of his left foot. The extension over years and the
      linear arrangement of the plantar papules suggested the possibility of a
      malignant melanoma. However the histological examination of 2 biopsies showed the
      structure of a common blue nevus. DISCUSSION: About a dozen cases of such papular
      plaque-type blue nevi have been described. Histologically they disclose the same
      cellular types than common blue nevi. In all the reported cases the course was
      benign; in our case the decision of abstention was sustained by this information.

PMID- 9615114
TI  - [Facial myofibroma of the newborn simulating sarcoma].
AB  - INTRODUCTION: Myofibromatosis is a rare but probably under estimated tumor.
      OBSERVATION: We report a case of a newborn presenting with a facial tumor
      suggestive of sarcoma. Discrepancy between clinical features and histologic
      pattern of angioma suggested the diagnosis of myofibroma. The diagnostic of
      myofibromatosis was made later by specific labelling (actin-smooth muscle) and
      was confirmed by major spontaneous involution. DISCUSSION: The histology of
      myofibroma associates fibrous and angiomatous patterns that may be confusing when
      examining a small biopsy. Due to confusing semiology and histology, subcutaneous
      myofibromas are certainly misdiagnosed and specific actin labelling (actin, HHF
      35) may be of interest. Myofibromas are the most frequent tumor among
      fibromatoses. The diagnosis should be suspected on the stony consistence of the
      tumor uncompatible with angiomatous histology. Contrary to multicentric
      myofibromas of which the prognosis depends on visceral involvement and
      compressions (72 p. 100 of fatal outcome), solitary subcutaneous myofibroma has a
      very good prognosis with spontaneous involution.

PMID- 9615113
TI  - [Aggressive cutaneous T-cell lymphoma associated with the presence of Epstein
      Barr virus. 2 cases].
AB  - INTRODUCTION: The factors of prognosis of the cutaneous T-cell lymphomas are less
      well known as those of the B-cell lymphomas and the role of the Epstein-Barr
      virus (EBV) is not yet definitively evaluated. CASE REPORTS: Two male patients
      aged 62 and 82 years had a mycosis fungoides with a lethal outcome. The first
      patient had mutilating facial tumors; the RNA m of EBV and the genome of EBV were
      demonstrated in the diseased skin. The second patient had an erythrodermic course
      with enlarged peripheral lymph nodes and circulating Sezary's cells; the genome
      of EBV was demonstrated by PCR in the diseased skin. DISCUSSION: The role of the
      EBV has already been demonstrated in peripheral aggressive T-cell lymphomas. In
      the mycosis fungoides, the EBV is associated with the lesions in 0 to 32 p. cent
      according to the published series. EBV associated T-cell lymphomas have a poor
      survival rate and the EBV infection may be associated with the expression of the
      multidrug resistant gene-1 (MDR-1) and the risk of a terminal hemophagocytosis.
      In our both patients the presence of the EBV in the lymphocytes of the skin
      lesions is also an argument in favour of the pathogenic role of the virus.

PMID- 9615115
TI  - [A case for diagnosis: neonatal Malassezia furfur pustulosis].

PMID- 9615116
TI  - [A case for diagnosis: epidermoid carcinoma complicating hypertrophic lichen
      planus of the leg].

PMID- 9615117
TI  - [Erysipelas. Recent data and current concept].

PMID- 9615118
TI  - [Residual acne lesions after treatment].

PMID- 9615119
TI  - [Question of the month: what is the role of the physician in associations for
      patients?].

PMID- 9615120
TI  - [Drug surveillance and topical drugs].

PMID- 9615121
TI  - [Urticaria caused by cold. 104 cases].
AB  - INTRODUCTION: Superficial and deep cold urticaria is a heterogeneous group of
      manifestations induced by exposure to cold (0 to 4 degrees C). Frequency is
      generally estimated at 2 to 3 p. 100. We studied retrospectively 104 patients
      meeting clinical, biological and therapeutic criteria of cold urticaria. PATIENTS
      AND METHODS: From 1981 to 1995, 1802 patients with urticaria were included in a
      standardized allergy survey. Among these patients, 104 met the criteria for the
      diagnosis of cold urticaria: positive test with 3 ice cubes placed on the skin
      for 5, 10 and 15 minutes or positive immersion test (immersion in 4 degrees C
      water for 15 minutes). Two groups of patients were excluded, those with systemic
      cold urticaria and those with minimal thermo-differential urticaria. RESULTS:
      Cold urticaria was found in 5.7 p. 100 of our urticaria patients, predominantly
      in young women. The triggering effect of cold was found at history taking in 71
      p. 100 of the cases. The urticaria was usually superficial, more rarely
      associated with deep and/or mucosal urticaria. General signs were uncommon. The
      three ice cube test demonstrated significative biological and immunological
      abnormalities. In 5 cases, discrete cryoprecipitate was found (4 cryoglobulins, 1
      cryofibrinogen). Although the search for an infectious agent was not conducted in
      absolutely all cases, there was no apparently remarkable association with
      infection the exception of VIH infection. Anti-H1 agents were given in 88.3 p.
      100 of the cases leading to short-term improvement. Follow-up is insufficient to
      evaluate long-term outcome. DISCUSSION: This retrospective survey of 104 cases of
      cold urticaria was compared with data in the literature, particularly with the
      small number of studies including a large number of patients. We conclude that
      the diagnosis of cold urticaria can be based on history taking alone and the
      three ice cube tests (prognosis value, indication of reaction threshold). An
      exhaustive search for the cause is not indicated. A search for cryopathy should
      however always be done and followed by a complete work-up in case of positivity.
      Clinical signs other than cold urticaria suggesting a pathological response to
      cold require complete investigations.

PMID- 9615122
TI  - [Scleroderma-like patch on the thigh in infants after vitamin K injection at
      birth: six observations].
AB  - INTRODUCTION: Texier's disease or pseudosclerodermatous reaction after
      intramuscular injection of vitamin K1 is well known in adults although only 1
      report of a case in a newborn was found in the literature. We report 6 cases.
      CASE REPORTS: Six infants (4 boys, 2 girls) developed "peau d'orange" skin
      lesions after the age of 6 months which was localized in the lower third of the
      medial aspect of the thigh. Initial rapid locoregional extension was followed by
      stabilization and then regression. In all 6 cases, histology showed lesions of
      the fascia and/or the deep hypoderma associated with variable mononuclear
      inflammatory infiltration and hyalin fibrosis. When performed, immunological
      studies (complement fixation, search for autoantibodies) were always negative or
      normal. No visceral involvement was found. DISCUSSION: A pseudosclerodermatous
      lesion of the lower third of the thigh occurred in 6 infants at the site of an
      intramuscular injection of vitamin K1 administered at birth. The history,
      clinical manifestations, histology and outcome of these cases are compatible with
      the diagnosis of Texier's disease. We discuss the role of the solvent in the
      Roche vitamin K1 injection. The pathogenesis of this side effect remains unknown.
      CONCLUSION: Texier's disease in infants after injection of vitamin K1 at birth is
      a stereotypic dermatosis. Diagnosis is based on history and clinical
      presentation. The causal effect of injectable vitamin K1 should be entertained
      whenever pseudosclerodermatous lesions are observed in a young child.

PMID- 9615123
TI  - [Treatment of accidental extravasation of antitumor agents with dimethylsulfoxide
      and alpha-tocopherol].
AB  - INTRODUCTION: The aim of this study was to test topical applications of
      dimethylsulfoxide and alpha-tocopherol for the prevention of ulcerations after
      antimitotic extravasation. METHODS: An open prospective study was conducted in 10
      patients in 4 different chemotherapy wards who had experienced infusion accidents
      leading to phlebitis (4 cases) or cellulitis (8 cases) including 2 at implant
      sites. Topical application of the dimethylsulfoxide alpha-tocopherol combination
      was initiated within the first hours and continued for 3 to 15 days. One patient
      was given dimethylsulfoxide alone. RESULTS: Necrosis was never observed. The
      implant sites were preserved and remained functional. CONCLUSION: The absence of
      secondary ulcerations and the preservation of the implant sites are clear
      advantages of this topical combination which should be used as first line
      treatment. Favorable results have been reported in the literature while other
      techniques used depend on the antimitotic agent and give variable results.

PMID- 9615124
TI  - [Cutaneous necrosis secondary to topical treatment of wart with 20 p. 100
      glutaraldehyde solution].
AB  - INTRODUCTION: A commercial 20 p. 100 formulation of glutaraldehyde was recently
      introduced for the treatment of plantar warts. The rhinopharyngopulmonary
      toxicity of glutaraldehyde is well known. Allergic skin reactions may also occur.
      We report a case of necrosis of the pulp of the greater toe during normal use of
      this product. CASE REPORT: A 7-year-old child consulted for major, dry and
      painful necrosis of the pulp of the greater right toe. Clinical examination
      suggested a caustic lesion. The only agent which could be incriminated was a
      daily application of a 20 p. 100 glutaraldehyde solution every day for 8 weeks.
      Local application of liquid nitrogen immediately before beginning the
      glutaraldehyde treatment may have been a favoring factor. After 6 weeks of local
      antibiotherapy, the lesion had not completely healed. DISCUSSION: In France,
      warts are not usually treated with 20 p. 100 glutaraldehyde. Used extensively in
      Great Britain, there have apparently been no major accident at concentrations
      under 10 p. 100. The recent report by a Japanese group indicating the efficacy
      and safety of 20 p. 100 glutaraldehyde has led to renewed interest in this
      treatment: necrosis has never been reported. In our case the necrosis occurred
      after normal use of the product. The caustic effect appears to dominate (role of
      concentration, pH?). Incidents due to sensitization have also been reported.
      Repeated cases of this type have led to the withdrawal of the product from the
      market in December 1995.

PMID- 9615125
TI  - [Painful nodular and plantar erythema in children].
AB  - INTRODUCTION: According to our knowledge, only twenty-three similar cases have
      been reported in the literature. Possible hypotheses for localised painful red
      nodules on the feet in children include erythema nodosum, neutrophilic eccrine
      hidradenitis, traumatic plantar urticaria, vasculitis and cold panniculitis. CASE
      REPORT: We report a typical case of painful erythematous plantar nodules of the
      child. A 13-yr-old boy was first seen by a paediatrician for intermittent fever.
      The fever was associated with red, painful nodules on the soles. He was unable to
      walk. Routine blood chemistry parameters were within normal limits.
      Histopathologic examination of lesional skin revealed an image of septal and
      lobular panniculitis with vasculitis. Direct immunofluorescence study was not
      contributive. With proper antibiotic therapy, pain resolved within one week while
      fever and nodules cleared within two weeks. DISCUSSION: Briefly, this observation
      concerns a child disease occurring as painful erythematous plantar nodules. The
      lesions are spontaneously resolutive and the children are in good health. Our
      observation should constitute a supplementary group with the same classical
      symptoms of nodular plantar painful erythema of the child but moreover
      accompanied by a septal and lobular panniculitis with vasculitis at the
      histological examination. Further studies are necessary to verify these
      hypotheses.

PMID- 9615126
TI  - [Eruptive epidermoid cysts secondary to erysipelas].
AB  - INTRODUCTION: Eruptive epidermoid cysts often occur following bullous skin
      diseases and their histopathological origin is from follicular or eccrine
      structures. CASE REPORT: A case of a patient who developed eruptive epidermoid
      follicular cysts following an erysipelas without bullous lesions is reported. The
      lesions disappeared secondarily to a relapse of the cutaneous infection.
      DISCUSSION: This association is rare but can be explained thinking to
      histogenesis of eruptive epidermoid cysts. The rapid resolution of these lesions
      occurring during a new inflammatory flare emphasize their tendency toward
      spontaneous resolution by extruding their contents.

PMID- 9615127
TI  - [Unilateral acro-keratoelastoidosis].
AB  - INTRODUCTION: Acrokeratoelastoidosis was first described by O. Costa in 1953. We
      report a new case with a unilateral localization. CASE REPORT: A 27-year-old
      woman had atypical acrokeratoelastoidosis lesions of the right hand and foot
      since adolescence. Diagnosis was confirmed by histology. DISCUSSION: Several
      cases of acrokeratoelastoidosis have been reported in the literature, but this
      case is novel because of the unilateral localization. We recall the
      characteristic features of this disease and emphasize the heterogeneous nature of
      the manifestations. Differential diagnosis is discussed for this disease which is
      one of the group of acral lenticular keratoses.

PMID- 9615128
TI  - [Cutaneous lupus erythematosus and buccal aphthosis after hepatitis B vaccination
      in a 6-year-old child].
AB  - INTRODUCTION: Although the hepatitis B vaccination tolerance is generally good,
      adverse effects, which are specially neurologic and cutaneous, have been observed
      and some cases of induced diseases with immunological disorders have been
      reported. CASE REPORT: A 6 year-old boy presented a cutaneous lupus erythematosus
      and a severe buccal aphthosis following hepatitis B vaccination. There was no
      clinical or biological symptom of systemic lupus erythematosus nor of Behcet's
      disease. Under chloroquine therapy, the cutaneous manifestations of lupus
      erythematosus disappeared quickly and those of buccal aphthosis improved.
      DISCUSSION: Hepatitis B vaccination side effects are probably in relation with a
      specific or non specific stimulation of the immune system. In our case, cellular
      immunity is perhaps involved through the HBs antigen. Considering the rarity of
      these side effects, an individual predisposition seems very likely.

PMID- 9615129
TI  - [Keratoacanthoma centrifugum marginatum. Possible etiological role of
      papillomavirus and therapeutic response to etretinate].
AB  - INTRODUCTION: Keratoacanthoma centrifugum marginatum is an uncommon
      keratoacanthoma of unknown etiology. We report a case suggesting a possible
      etiological role for a papillomavirus. Etretinate was an effective treatment.
      CASE REPORT: A 65-year-old woman had keratoacanthoma centrifugum marginatum of
      the antero-inferior aspect of the lower third of the right leg for 5 years.
      Fifteen years earlier, an infection had occurred at the same site after a trauma
      and was treated by oral antibiotics. Surgical exeresis was difficult due to the
      wide spread of the lesion. Etretinate given at an initial dose of 1 mg/kg/d for 6
      weeks then reduced by half for 2 months led to nearly complete cure. DISCUSSION:
      Keratoacanthoma centrifugum marginatum, verrucous carcinoma and epidermal
      carcinoma have some histological characteristics in common, suggesting a possible
      common etiological agent which could be certain strains of the human
      papillomavirus (HPV). In our case etretinate provided cure, possibly due to its
      antitumoral activity and perhaps due to its antiviral activity. The presence of
      koilocytes suggested HPV infection which was confirmed by PCR. This test does not
      however provide proof of the etiological role of HPV. We are currently studying
      the presence of HPV in keratoacanthomas and their possible etiological role.

PMID- 9615130
TI  - [Rosacea with ocular involvement in a child].
AB  - INTRODUCTION: Rosacea ia an uncommon facial eruption in children. We report a
      case of rosacea associated with a specific episcleritis. CASE REPORT: A 10-year
      old girl consulted for an erythematous papular and pustular eruption of the mid
      face of 1 month duration. The child complained that she had had a red painful
      right eye for 6 months. There was no argument for acne, periorificial
      granulomatous dermititis or for sarcoidosis. The ophthalmological examination
      gave the diagnosis of ocular and cutaneous rosacea. Oral antibiotics followed by
      erythromycin gave favorable results for both skin and ocular lesions. DISCUSSION:
      Ocular involvement is a frequent complication of rosacea in adults. It is
      exceptional in children in whom rosacea is in itself rare. The presence of
      blepharitis, keratoconjunctivitis or episcleritis may suggest the diagnosis in a
      child with a mid facial eruption. As in the adult, skin and ocular rosacea
      responds well to prolonged oral antibiotics. The choice of the antibiotic depends
      on the age of the child. Cyclins are not authorized in children under the age of
      8 years.

PMID- 9615131
TI  - [External photoprotective agents and cutaneous cancers].

PMID- 9615132
TI  - [Apropos of idiopathic longitudinal melanonychia].

PMID- 9615133
TI  - [Hypertriglyceridemia induced by interferon].

PMID- 9615134
TI  - [A case for diagnosis: penile ulcer induced by foscarnet].

PMID- 9615135
TI  - [Management of diaper dermatitis].

PMID- 9615136
TI  - [Cutaneous reactions to orthopedic implants].

PMID- 9615137
TI  - [Hyper IgD syndrome].

PMID- 9615138
TI  - [Question of the month: is electrical hair removal a current practice in
      dermatology?].

PMID- 9615139
TI  - [Long-term outcome at adjacent levels of lumbar arthrodesis].
AB  - Posterolateral lumbar fusion is commonly recognized to have a significant effect
      upon the more proximal unfused segments. Wether these effects are clinically
      significant remains unclear. Long term studies with standardized follow-up are
      scarce. The purpose of this study was to examine the long term roentgenographic
      and clinical effects of posterolateral fusion upon the 3 cephalad unfused
      segments. The levels below a floating fusion were also examined. The factors
      promoting the occurrence of degenerative changes on standard or dynamic x rays
      were also investigated with a multivariate analysis model. 102 patients who
      underwent a posterolateral fusion were retrospectively reviewed with an average
      follow-up of 8.9 years. 39 patients (group I) were fused for low back pain caused
      by isthmic lysis spondylolisthesis, 15 (group II) for degenerative disc disease
      and 48 (group III) in addition to a posterior decompression for a lumbar spinal
      stenosis. Pre and postoperative standard and dynamic roentgenograms were compared
      in order to study: evolution of the disc space height, modifications in the
      angular and antero-posterior mobility, modifications in the antero-posterior
      displacement of the vertebral bodies. Degenerative changes were frequent. 49 per
      cent of the patients demonstrated a severe disc space narrowing, 30 per cent
      developed a degenerative spondylolisthesis, 32 per cent an angular hypermobility
      and 35 per cent an antero-posterior hypermobility. Only one factor was found to
      increase significantly the occurrence of degenerative changes: the indication of
      lumbar fusion. Degenerative changes were significantly more frequent in group
      III's patients. However, no significant correlation was found between the
      roentgenographic findings and the final functional results and only 8 patients
      required a new surgery. These results may suggest that posterolateral fusion
      accelerates the development of degenerative changes in adjacent discs if the
      fusion is performed on a degenerative spine.

PMID- 9615140
TI  - [Long-term osseous changes in the posterior arch after laminectomy for lumbar
      stenosis].
AB  - PURPOSE OF THE STUDY: Many studies have indicated favorable results of
      decompressive surgery for symptomatic lumbar spinal stenosis. However, little is
      known about the osseous changes that occur at the operative sites. Postacchini in
      1992 and Chen in 1994 have studied, only from plain radiographs, osseous changes
      at the operative sites, and have suggested that bone regrowth possibly affects
      the neurologic result. The aims of this study were: to assess bone regrowth at
      the operative site, to compare the bone regrowth rate calculated from plain
      radiographs and CT-Scan examinations, to determine the effects of bone regrowth
      on clinical outcome, to investigate the factors promoting the bone regrowth.
      MATERIAL AND METHOD: 28 patients who underwent decompressive surgery for lumbar
      spinal stenosis were retrospectively studied with an average follow-up of 8.4
      years. In order to evaluate the degree of bone regrowth at the posterior arch,
      early postoperative radiographs and CT images of the operative sites were
      compared with those obtained at final follow-up. Bone regrowth at the sites
      operated upon was evaluated as a percentage of regrowth of the original
      laminectomy site based upon plain radiographs and CT images. RESULTS:
      Decompressive lumbar spinal stenosis is responsible for bone regrowth at the
      operative site in most patients. However, this regrowth was mild, the mean bone
      regrowth rate evaluated from plain radiographs was 12 per cent in average and the
      obtained from CT images was 8.2 per cent in average. Changes were found to be
      predominant at the facet joint level compared to the pedicle level. The
      evaluation of regrowth obtained from plain films and CT image examinations were
      compared. Radiographs seem to overestimate bone regrowth. Postoperative spinal
      instability was statistically significantly associated with new bone development.
      This variable was the only factor that affected the degree of bone regrowth. No
      relationship between bone regrowth and clinical outcome was found. DISCUSSION AND
      CONCLUSION: Natural course of laminectomy defect includes probably new bone
      formation in most patients. New bone results from gradual regrowth of the laminae
      and articular processes partially resected at surgery and from coalescence of
      islets of bone tissue within the tissue filling the laminectomy defect. In the
      present study bone regrowth rate was moderate but in other ones it was marked. If
      some factors (like postoperative destabilization) promoting bone regrowth were
      identified many remain unknown. Factors influencing rapidity of regrowth
      progression remain also unknown. Patient's intrinsic features such as spinal
      stenosis characteristics are probably closely related to quantitative and kinetic
      characteristics of regrowth. Consequences of bone regrowth are also variable: in
      some cases regrowth may reproduce pathological conditions identical previous
      ones, in other ones new bone spreads around the dura a mater without any nerves
      roots compression. Study of bone regrowth requires further research including
      prospective studies and using a more precise method for the regrowth evaluation.

PMID- 9615141
TI  - [Arthroscopic removal of intra-articular loose foreign bodies of the elbow].
AB  - PURPOSE OF THE STUDY: We have retrospectively studied the results of arthroscopic
      removal of loose bodies in the elbow. The aim of the study was to determine if
      the etiology of the loose bodies could be considered as a criteria for technical
      difficulty and clinical prognosis. MATERIAL: 16 patients (11 men and 5 female)
      had an elbow arthroscopy for loose bodies removal. Their average age was 29.5
      years (range: 16-49). The post-operative results were recorded in their medical
      files with an average follow-up of six months. METHODS: In each case we have
      determined the etiology of the intra-articular loose bodies. The results were
      analyzed according to technical difficulty and clinical outcome. RESULTS: The
      etiology of the loose bodies was 8 chondromatosis, 4 osteochondritis dissecans
      and 4 post-traumatic osteoarthritis. The removal of the loose bodies was possible
      in 13 cases. Three arthroscopies were interrupted because of arthritic joint
      space narrowing. Twelve patients with primary chondromatosis and osteochondritis
      dissecans were improved. We did not find any significant clinical improvement in
      osteoarthritic elbows. A correlation between the results and the etiologies could
      therefore be shown. DISCUSSION: In arthroscopic removal of elbow loose bodies,
      technical difficulties and clinical results are correlated to the etiology of the
      loose bodies and also to the statement of the osteochondral surfaces.

PMID- 9615142
TI  - [Femoropatellar osteoarthritis treated by prosthesis. Retrospective study of 50
      implants].
AB  - MATERIAL AND METHODS: 51 prosthesis were performed in 47 patients and were
      studied in order to assess long term results. One patient was lost for follow up.
      The diagnosis was: primitive arthritis in 48 knees and post traumatic arthritis
      in 3 knees. 25 knees had patellofemoral subluxation, 16 patients had been
      previously operated on patellofemoral joint. The average age at the time of
      surgery was 60.5 years and follow up time averaged 3 years. 22 prosthesis had
      more than 4 years follow-up. The operations were performed using a lateral
      approach with tibial tubercle osteotomy and lateral patellar retinaculum release.
      The trochlear component was asymetric and made of chrome cobalt alloy; the
      patellar component was shaped in polyethylene. Both components were cemented.
      RESULTS: Using the Guepar scoring system, 41 (82 per cent) PFA were rated
      excellent or good and 9 poor. Post operative roentgenograms demonstrated
      patellofemoral alignment in all knees, even in cases of preoperative patellar
      subluxation, without tilting of the patella. Follow up roentgenograms
      demonstrated progressive but moderate deterioration of the tibio femoral joint in
      9 cases. In 3 cases, more severe tibio femoral arthritis were treated by T.K.R
      one to three years after P.F.A. In one of these knees, we discovered an
      asymptomatic loosening of trochlear component. The last 6 poor results were
      always due to persistent pain. DISCUSSION: The purpose of this study was to
      assess the results of P.F.A. and to clarify the indications. It appears that the
      82 per cent success rate of this study may be compared with the results of
      literature. All the authors have found P.F.A. to be a viable solution, preferable
      to patellectomy (even in older patients) or isolated patellofemoral realignment.
      The clinical and radiological results did not deteriorate with time. Persistent
      patellofemoral malalignment was not observed in this study thanks to the use of a
      lateral approach. The presence of tibio femoral arthritis adversely affected the
      outcome, but accelerated changes on the tibio femoral joint after P.F.A. were not
      observed.

PMID- 9615143
TI  - [A protocol of in vivo 3D experimental evaluation of global posture and motion of
      the spine].
AB  - PURPOSE: The aim of his study was to assess 3D global posture and movement of
      body segments, especially for scoliotic subjects. As scoliosis is a three
      dimensional deformity, it needs three-dimensional evaluation and correction, but
      there is no mean today to get 3D dynamic examination of the whole body. MATERIAL
      AND METHODS: Using opto-electronic methods, an experimental protocol was
      established to compare the pre- and post-operative results of treatment. Firstly,
      the reliability of the protocol was tested in healthy adult subject. Secondly, a
      reference group of 15 healthy teenagers was analysed Besides, first scoliotic
      subject in pre- and post-operative situations were followed. The markers fixed on
      the skin allowed us to calculate the position of the head, the pelvic, the
      shoulders and the spinal axis, during a static trial and motions. RESULTS: The
      reliability of the protocol was satisfactory (standard deviation (s) < 5.4
      degrees in a flexion movement). The inter-subject variability was greater for the
      position of the head than for the pelvis, the shoulders or the spinal axis. The
      scoliotic patient showed a straightening of the whole body in the three anatomic
      planes. One month after treatment, the range of motion were reduced (+13.8
      degrees for the pelvic flexion during a flexion movement), but six months after
      surgery they were greater than before (+14.7 degrees). CONCLUSION-DISCUSSION:
      Many systems have been proposed to measure the motion of the trunk, but they were
      not three-dimensional. The opto-electronic method is a non invasive, external and
      dynamic system.

PMID- 9615144
TI  - [Treatment of complex bicondylar fractures of the tibial plateau by semi-circular
      anterior diaphyseal-epiphyseal plate].
AB  - PURPOSE: One third of all tibial plateau fractures are bicondylar, and some of
      them have posterior separation and metaphyseal comminution. In these cases, it
      may be difficult to reconstruct at the same time tibial axis, bone continuity and
      articular surface. The authors propose a new method for the treatment of these
      fractures. METHOD: Reduction is facilitated by permanent extension using a
      transcalcaneal pin. Knee approach involves elevation of the anterior tibial
      tuberosity (ATT). The new plate used is available for each side. It presents an
      epiphyseal surrounding anterior part applied on the epiphysis above the ATT and a
      vertical part applied medially. All the separated fragments are temporarily
      stabilized by pins which are used to guide the definitive plate. For this an
      aiming plate duplicating the epiphyseal part of the definitive plate is used to
      insert the pins. Then, the definitive plate is slided without removing the pins.
      The pins also guide cannulated screws. MATERIAL AND RESULTS: Out of 32 tibial
      fractures treated from January 1994 to June 1996, 3 cases were operated on using
      this method. All 3 cases have a frontal separation fracture, cartilage depression
      and metaphyseal complex fracture. Perfect articular reconstitution, fusion and
      axis were obtained. A fourth case was a proximal tibial fracture, very close to a
      total knee prosthesis. DISCUSSION: Complex bicondylar fractures are one of the
      most difficult fractures to treat. Identification of the lesions should be
      envisioned before operation and especially the separated posterior fragments. The
      peroperative extension combined with the anterior approach with ATT elevation
      provided a complete view of intra articular fracture and correction of the axis.
      The semi-circular anterior plate allowed the fixation of all the fragments, and
      furthermore, the original procedure using temporary pins to guide the definitive
      plate has avoided to loose the reduction.

PMID- 9615145
TI  - [Surgical treatment of the rheumatoid forefoot by realignment using th dorsal
      approach].
AB  - PURPOSE OF THE STUDY: The aim of this study was to appreciate the results of the
      modified Fowler's procedure in the surgical treatment of forefoot deformities due
      to rheumatoid arthritis. MATERIAL AND METHOD: If the principles of the
      metatarsophalangeal resection through a dorsal transverse incision were
      conserved, we progressively modified the initial procedure with renunciation to
      the plantar skin incision, preservation of a skin bridge between the medial and
      transverse dorsal approach, using centro medullary pins to hold in position toes
      alignment and making an arthrodesis of the first metatarsophalangeal joint. Ten
      patients (17 surgical procedures) were clinically and roentgenographically
      reviewed at an average follow-up of 27.3 months (Range : 12 and 53 months).
      RESULTS: Clinical results according to the Gainor scale showed an increase of the
      overall score from 3.4 points to 11.2 points at revision. Twelve foot were rated
      excellents and five goods. Seventy per cent of patients had no pain and 58 per
      cent used a normal footwear. Radiographical and clinical analysis showed that an
      egyptian foot remained in nine cases, podoscopic examination revealed frequently
      a lack of footrest on lateral toes without functional implications. Delayed wound
      healing were observed in four cases with good evolution. CONCLUSION: With this
      surgical procedure, our functional results were encouraging and we recommend it
      in severe deformities of the rheumatoid foot with fixed metatarsophalangeal
      dislocations and bone defect of the metatarsal heads.

PMID- 9615146
TI  - [Value of the surgical approach through the patellar tendon for intramedullary
      nailing of the tibia and the femur].
AB  - The goal of this study was to propose a new approach of the upper tibia for
      intramedullary nailing. Since two years, the authors performed a transversal skin
      incision superior to the distal end of the patella. The patellar tendon is
      dissociated and the tibia is perforated through the anterior intercondylar area.
      The advantages of this approach versus classical techniques are discussed. This
      approach allows isolated tibial or femoral nailing but also both nailings during
      the same procedure.

PMID- 9615147
TI  - [Pubic osteitis caused by Salmonella indiana. Apropos of a case].
AB  - INTRODUCTION: The authors report the case of a pubic osteomyelitis caused by a
      salmonella indiana bacterium in a 12 year old child. CLINICAL CASE: A post
      traumatic left side pubic pain in a 12 year old child was associated to feverish
      and inflammatory syndrome, without any predisposing factor. Salmonella Indiana
      bacterium was found in fecal samples. Radiographs showed an asymetry of the
      iliopubic branches and an irregularity of the upper left border of the pubic
      branch. Bone scan showed a public hyperfixation and CT revealed a left-sided
      pubic osteolysis. The bacteriological examination of the osseous biopsy confirmed
      the presence of Salmonella Indiana bacterium. Recovery was obtained within 5
      months with intravenous antibiotherapy. DISCUSSION: Since 1987, an increase of
      minor salmonella infections and particularly of Salmonella Indiana bacterium can
      be observed in metropolitan France (250 isolated in 1991). This increase is not
      experienced in Martinique. The contamination mode is yet unknown and the osseous
      localization is secondary to bacteriema. The patient had no predisposition
      excepted a chronic digestive carrier. This localization is unfrequent in
      children. The diagnostic has been achieved by bacteriological samples and osseous
      biopsy. The treatment based was on third generation cephalosporins and on
      quinolones.

PMID- 9615148
TI  - [Post traumatic myositis ossificans of the iliopsoas muscle. Apropos of a case
      with review of the literature].
AB  - A case of traumatic myositis ossificans of the iliopsoas muscle in a 13 year old
      ballet dancer is presented. A history of multiple minor injuries to the region of
      the left hip in addition to the radiographic appearance of calcification were
      indicative of ectopic bone formation. The lesion was explored surgically because
      of the clinical symptoms of the coexistant femoral hernia as well as to obtain
      biopsy material to exclude a soft tissue tumor. Histological examination
      demonstrated the zoning effect of myositis ossificans with patterns varying from
      a cellular central zone to a peripheral one of fairly well oriented bone. The
      patient remains symptom-free and no radiographic evidence of recurrence was
      observed four years postoperatively.

PMID- 9615149
TI  - [Long-term results of condylar reconstruction using patella as vascularized
      graft].
AB  - PURPOSE OF THE STUDY: In 1966, R. Merle d'Aubigne published 4 cases of
      unicondylar destructions (due to trauma or tumor) reconstructed with the patella
      replacing the joint surface. Since this time the same technique has been used in
      6 other cases. The results of these 10 patients are studied. MATERIAL AND METHOD:
      Six of the examined patients were treated initially for a giant cell tumor, 1 for
      a low-grade osteosarcoma, and 3 for post traumatic arthritis. The patellar
      transplant remains vascularized by it's supero-medial vascular bundle. The
      femoral condyle was affected in 9 cases, the tibial plateau in one. RESULTS: The
      long term follow-up of these 10 patients revealed unexpected satisfactory
      results. None of the operated knees was clinically "excellent", due to
      instability or axial deterioration, but function remained correct, with a good
      range of motion, active professional possibilities, and, often, regular practice
      of some sports, like skiing or tracking. Function was not correlated with
      radiological aspect. The arthritic remodeling of the knee was obvious in all of
      the cases, and regularly increasing. Five of the 10 knees had to be reoperated
      (one or several times): 3 during the first months of follow-up (1 for sepsis, 2
      for supracondylar fractures), 5 during the first years, to improve function (2
      arthrolysis, 2 valgus osteotomies, 1 loose bodies removal). Three patellar
      plasties had to be converted into a total knee prosthesis, after 8, 27 and 40
      years. The follow-up of the 7 patients still walking on their patellar plasty is
      of 2, 4, 17, 19, 24, 24 and 25 years. DISCUSSION AND CONCLUSION: Condylar
      reconstruction using a vascularized patellar transplant is mechanically speaking
      an approximative, obsolete and rather rough procedure. Nowadays one would prefer
      a knee prosthesis, with or without auto or allografts, preserving the patella.
      The immediate functional result would certainly be better, but the future remains
      uncertain. The patellar plasty can delay for 10, 20 years or even more the time
      of a prosthesis. This technique might also be useful in countries where
      prosthetic implants are not easily available.

PMID- 9615150
TI  - Iohexol: effects on uptake of radioactive iodine in the thyroid and on thyroid
      function.
AB  - RATIONALE AND OBJECTIVES: The authors attempted to determine whether the use of
      nonionic contrast media causes uptake of iodine by the thyroid to be blocked and
      whether use of these agents could cause iodine-induced hyperthyroidism. MATERIALS
      AND METHODS: Twenty-eight persons, including 22 with thyroid disease, were
      included in the study. Subjects underwent computed tomography (CT) of the thyroid
      after injection of 100 mL of iohexol. Thyroid function variables were measured
      before CT scanning and 1 week and 1 month later. In 16 subjects, uptake of iodine
      131 by the thyroid was measured before and 1 week after CT. RESULTS: I-131 uptake
      was reduced to 53.4% at 1 week after the injection of iohexol but became normal
      within a few weeks (followed up in one patient). An accelerated escape of I-131
      from the thyroid was seen during the 1st days after the iohexol administration.
      Eight of 22 patients with an underlying thyroid disease had a temporary change in
      thyroid function. In four patients, the serum thyrotropin level was increased 1
      week after the iohexol administration. In four other patients, temporary
      hyperthyroidism developed during the following months. CONCLUSION: Iohexol can be
      used in patients with an underlying thyroid disease, but close monitoring in the
      following months is necessary.

PMID- 9615151
TI  - Efficacy of prone positioning during intravenous urography in patients with
      hematuria or urothelial tumor but no obstruction.
AB  - RATIONALE AND OBJECTIVES: The authors prospectively explored the efficacy of
      using prone positioning during intravenous urography to improve diagnostic
      visualization and eliminate the need for retrograde pyeloureterography in
      patients with no obstruction but with hematuria, history of urothelial tumor, or
      abnormal results of urine cytology. MATERIALS AND METHODS: Prone radiography was
      added to the usual intravenous urography protocol in 510 patients (347 men, 163
      women) without urinary tract obstruction. Interpretations of intravenous urograms
      and recommendations for retrograde pyeloureterography were made before and after
      evaluation of the prone image. RESULTS: Confidence in the urographic
      interpretation was improved with acquisition of the prone radiograph in 100 of
      510 patients (19.6%) (95% confidence interval, 82.1, 118). Retrograde
      pyeloureterography was obviated in 46 of 510 patients (9.0%) (95% confidence
      interval, 33.1, 58.9). The prone image was most helpful in evaluating the distal
      ureters (sacral and pelvic segments). CONCLUSION: Prone patient positioning
      during intravenous urography is useful when complete visualization of the upper
      urinary tract is desirable. Obtaining the additional image is cost-effective,
      even when only a few retrograde pyeloureterography studies are obviated.

PMID- 9615152
TI  - CT attenuation of fluid in breast cysts.
AB  - RATIONALE AND OBJECTIVES: The authors' purpose was to determine whether computed
      tomographic (CT) attenuation values of fluid in breast cysts could be in the
      range of values for soft tissue and could be correlated with protein content of
      the fluid. MATERIALS AND METHODS: Aspirate samples from 10 simple breast cysts
      were analyzed for protein content, and CT attenuation values were calculated by
      means of a breast phantom. A corrected attenuation value for breast-cyst fluid
      was calculated by using sterile water as a control. RESULTS: The mean corrected
      attenuation value for the cyst aspirate was 28.1 HU; most simple cysts have an
      attenuation value of only 10 HU. Protein concentration ranged from 0.9 to 2.4
      g/dL. A significant, almost linear relationship was noted between protein content
      and attenuation value of cyst fluid (r = .85, P < .01). CONCLUSION: The CT
      attenuation values of breast cysts can be in the range of those of soft tissue.
      This high attenuation value is correlated with the high protein content of breast
      cyst fluid. Therefore, an apparent circumscribed soft-tissue mass seen within the
      breast at CT may represent a simple cyst.

PMID- 9615153
TI  - Calvarial eosinophilic granuloma: diagnostic models and image feature selection
      with a neural network.
AB  - RATIONALE AND OBJECTIVES: The authors analyzed the accuracy of diagnostic
      features used by an artificial neural network compared with logistic-regression
      analysis in the diagnosis with computed tomography (CT) of calvarial eosinophilic
      granuloma. MATERIALS AND METHODS: Thirty-one of 167 patients with calvarial
      lesions were found to have eosinophilic granuloma. Clinical and CT data were used
      for logistic-regression and neural network models. Both models were tested by
      using the leave-one-out method. The final results of each model were compared by
      means of the area under the receiver operating characteristic curve (Az).
      RESULTS: Identification of eosinophilic granuloma was significantly more accurate
      with the neural network than with logistic regression (Az = 0.9846 +/- 0.0157
      [standard deviation] vs 0.9117 +/- 0.0373) (P = .001). The most important
      diagnostic features identified with the neural network were patient age and
      marginal sclerosis. For logistic regression, the most important features were
      age, shape, and lobularity. CONCLUSION: The neural network is a useful tool for
      analyzing the features of calvarial eosinophilic granuloma. Age and marginal
      sclerosis are important diagnostic features.

PMID- 9615154
TI  - Role of sodium in contrast medium-induced polymorphic ventricular tachycardia:
      results in a rabbit model of lengthened QT interval.
AB  - RATIONALE AND OBJECTIVES: The authors (a) compared the proarrhythmic effects of
      ioxaglate (152 mmol/L sodium) and iohexol (no sodium) in a rabbit model and (b)
      assessed the effect of adding 150 mmol/L sodium to isotonic iohexol. MATERIALS
      AND METHODS: Either ioxaglate (320 mg of iodine per milliliter) or iohexol (350
      mg of iodine per milliliter) was selectively injected into the right coronary
      artery (1.5 mL over 30 seconds) of 10 rabbits, some of which also received the
      alpha 1-adrenergic receptor agonist methoxamine. To validate the model, the class
      III antiarrhythmic agent clofilium was injected intravenously during methoxamine
      infusion. Frontal electrocardiography was performed continuously to detect
      polymorphic ventricular tachycardia (PVT). In a second study, the authors
      assessed the frequency of arrhythmias after injection of isotonic iohexol
      solution (145 mg of iodine per milliliter), either alone or with 150 mmol/L
      sodium. RESULTS: Methoxamine significantly lengthened the QT, QTc, and RR
      intervals (P < .05). The use of clofilium alone induced no PVT, whereas five of
      eight methoxamine-infused rabbits developed PVT after clofilium injection (P =
      .03). Both contrast media prolonged the repolarization period. Iohexol alone
      induced a higher frequency of PVT than did ioxaglate alone (P = .0006).
      Methoxamine infusion did not potentiate the frequency of PVT in the ioxaglate
      injected rabbits. The addition of sodium to isotonic iohexol prevented the
      occurrence of PVT (P = .0006). CONCLUSION: Although ioxaglate prolonged the
      repolarization period, it did not cause a higher frequency of arrhythmia when
      injected in association with methoxamine. Iohexol, which contains no sodium,
      induced a high frequency of arrhythmia. The addition of a physiologic
      concentration of sodium to isotonic iohexol can prevent ventricular arrhythmias.

PMID- 9615155
TI  - Quality evaluation of radiographic contrast media in large-volume prefilled
      syringes and vials.
AB  - RATIONALE AND OBJECTIVES: The authors compared the particle contaminations of
      radiographic contrast media packaged in large-volume prefilled syringes and
      vials. MATERIALS AND METHODS: Particle counting was performed for four contrast
      media packaged in large-volume prefilled syringes (iohexol, ioversol, ioversol
      for angiography, and ioxaglate) and three contrast media packaged in vials
      (iohexol, ioversol, and ioxaglate). X-ray emission spectrometry was performed to
      characterize the individual particles. The amount of silicone oil in the syringe
      was quantified with infrared spectrophotometry. RESULTS: The particle
      contamination in syringes containing ioversol was higher than that in syringes
      containing iohexol or ioxaglate. Particle contamination in the vials was
      relatively low, except with ioxaglate. X-ray emission spectrometry of the
      components of the syringe and vial showed that the source of particles was
      internal material released from the rubber stopper or inner surface. CONCLUSION:
      The particle counts for contrast media packaged in syringes and vials varied
      considerably among the different contrast media and were related to the amount of
      silicone oil on the inner surface and rubber piston of the syringe.

PMID- 9615157
TI  - Accuracy of mammographic appearances after breast fine-needle aspiration.

PMID- 9615156
TI  - The pediatric skull: appearance in health and disease.

PMID- 9615158
TI  - Laparoscopic ultrasound in abdominal surgery.
AB  - Laparoscopic ultrasound combines the advantages of diagnostic laparoscopy with
      peroperative ultrasonography. This new technique allows visualization of deep
      structures that are not palpable. The technical aspects of this technique and its
      applications in abdominal surgery are described. The main indications are the
      search for common bile duct stones during a laparoscopic cholecystectomy and the
      assessment of the spread of abdominal cancers. The information obtained from
      laparoscopic ultrasound can influence the therapeutic management.

PMID- 9615159
TI  - The influence of somatostatin on postoperative outcome after elective pancreatic
      surgery.
AB  - A series of 34 patients with pancreatic resections was evaluated with respect to
      the occurrence of local and general complications. Two groups were compared,
      depending on whether or not treatment with somatostatin was instituted.
      Postoperative morbidity and mortality were less frequent when somatostatin was
      given (resp. 50.0 and 5.5%) than when it was omitted (resp. 68.7 and 31.2%). Less
      complications were observed after resections performed for chronic pancreatitis
      than for pancreatic cancer in the non somatostatin-treated group. It is concluded
      that somatostatin treatment may be beneficial in preventing complications after
      elective pancreatic surgery.

PMID- 9615160
TI  - Five years of surgical experience with peritoneal dialysis.
AB  - In this study, we evaluate retrospectively five years experience with the Swann
      Neck Missouri DC catheters. Sixty three catheters are placed in 51 patients. The
      total observation period is 695.6 months and the average time is 13.6 months per
      patient. The last 21 catheters are coiled type. Infectious complications remain
      the most worrisome problem in peritoneal dialysis. Exit site infections are seen
      in 24%, tunnel infections in 8%, peritonitis in 38% and abdominal hernias in 16%
      of the patients. The results in our series (peritonitis every 29.0 patient
      months) are in accordance with data from the literature. The combination of a
      good surgical technique and an efficient postoperative attendance have reduced
      this frequency. In the situation of a tunnel infection, surgical removal remains
      the treatment of choice. To prevent an exit site infection, the entry port must
      be well nursed and protected. A coexisting abdominal hernia can be repaired
      during the implantation procedure. Fourty six peritoneal dialysis catheters have
      been removed. Transplantation and death are the main reasons (59%).

PMID- 9615161
TI  - Classic versus endoscopic perforating vein surgery: a retrospective study.
AB  - PURPOSE AND METHODS: In this retrospective non-randomized study the results of
      the FELDER technique (n = 29) were compared to two endoscopic techniques for
      ligation of incompetent perforating veins: using a mediastinoscope (n = 19) and
      laparoscopic instruments (n = 57). The indication was a venous ulcer in nine,
      five and thirteen patients respectively, lipodermatosclerosis in thirteen, five
      and twenty-four, and simple varicose veins in the remaining patients (NS).
      RESULTS: The mean number of interrupted perforating veins was 4.2, 2.4 and 3.8 (p
      < 0.05). The mean hospital stay was 3.5, 1.9 and 1.6 days (p < 0.0001). The mean
      period of convalescence was 8.7, 4.1 and 3.7 weeks (NS). The number of
      complications was 9 (suralis lesion 4, pain/swelling 4, wound problem 1), 6
      (saphenous lesion 3, pain/swelling 3) and 15 (pain/swelling 14, deep venous
      thrombosis 1) (NS). Ten patients were lost to follow-up (five, two and three).
      Respectively 19, 12 and 45 patients were satisfied with the end-result. The
      condition had worsened in one, two and three patients (NS). During the short
      follow-up period all ulcers healed and there was no recurrence. CONCLUSIONS: The
      endoscopic techniques produce results comparable to the FELDER procedure, with
      smaller scars and a tendency towards a faster recovery.

PMID- 9615162
TI  - Abdominal aortic aneurysms in octogenarians.
AB  - The decision on whether to operate or not abdominal aortic aneurysms (AAA) in
      elderly depends on the relative risk of the operation versus the natural course
      of the unoperated AAA. From January 1984 to December 996, 138 patients, aged 80
      years and older, were referred to our department for an aneurysm of 40 mm or more
      (transverse diameter) of the infrarenal abdominal aorta (95 asymptomatic, 15
      painful, and 28 ruptured AAA). For 58 patients with asymptomatic AAA, operation
      was denied at referral because of transverse diameter less than 50 mm (n = 21),
      patient refusal (n = 10) or unacceptable operative risk or poor general condition
      (n = 27). Thirty-four of these observed AAA were ultimately operated after a mean
      delay of 41 months because of aneurysm enlargement (n = 15), aneurysm tenderness
      (n = 6) or rupture (n = 13). Overall, 52 patients had immediate (n = 37) or
      delayed (n = 15) elective repair of their AAA, with an in-hospital mortality of
      5.7%. Urgent operation was done for 21 patients with a painful AAA. Six patients
      died at hospital (28% mortality rate). Emergent surgery was applied to 41
      patients with ruptured AAA (including 13 AAA who ruptured during surveillance).
      The operative mortality in this subgroup attained 68%. Follow-up for the 77
      survivors and the 24 non-operative patients averaged 43 months. The 5-year
      survival (operative mortality included) is 47% for electively operated patients,
      30% for urgently and 20% for emergently operated patients. For comparison, the 5
      year survival of an age and sex matched Belgian population is 63%. For the 24
      medically followed AAA, the 5-year survival was 33%. In six cases, the cause of
      death was rupture of the AAA. Of the 58 patients for whom operation was initially
      not considered, 19 (33%) presented AAA rupture (13 operated in emergency and 6
      who never came to surgery). The operative outcome of AAA repair in octogenarians
      is less favourable than in the younger age group (3.6% mortality after elective
      repair, 44% after operation for AAA rupture, according to our institution data).
      The authors conclude that AAA surgery should not be denied to octogenarians on
      the basis of advanced age alone. They recommend a straightforward surgery for
      otherwise healthy octogenarians with AAA of 50 mm diameter, surveillance up to 60
      mm for high-risk patients and no surgery for unfit, bedridden or demented
      patients.

PMID- 9615163
TI  - Free hydatid cyst only covered with germinative membrane disrupted from fibrotic
      capsule in the peritoneal cavity: a case report.
AB  - Echinococcosis, an endemic disease on the Asian continent, is caused by
      ecinococcus granulosus and rarely ecinococcus alveolaris. Although it occurs
      frequently in the liver and the lung, it can be localized in all tissues and
      organs. The purpose of this study is to report a rare localization and the
      complication of hydatid cyst in the pelvis : it pushed forward and upward the
      urine bladder and there was bilateral hydroureteronephrosis causing uraemia
      because of outflow obstruction. To our knowledge, a similar case has not been
      published before in English literature.

PMID- 9615164
TI  - Richter's femoral hernia: a clinical pitfall.
AB  - A.G. Richter described in 1777 a hernia in which the antimesenteric part of the
      small intestine was incarcerated. We demonstrate in the article the diagnostic
      pitfalls of the Richter's femoral hernia. The physical signs consist of vague
      abdominal complaints, swelling in the groin but usually no symptoms of intestinal
      obstruction. The Richter's femoral hernia can be complicated by a stenosis in the
      initially incarcerated distal ileum.

PMID- 9615165
TI  - Successful bridge to transplantation with Pierce Donachy (Thoratec) ventricular
      assist device.
AB  - Biventricular assistance with the Thoratec ventricular assist device was
      performed in a 48-year-old man waiting heart transplantation since 6 months.
      Indication for circulatory support was considered because of the development of
      progressive irreversible right heart failure with deterioration of the hepatic
      and renal functions. Orthotopic heart transplantation was performed after 13 days
      of circulatory support. No complications occurred during the assistance and in
      the posttransplant period. The patient was discharged on day 21 after
      transplantation. Five months after transplantation he is well and alive.

PMID- 9615166
TI  - Surgical thromboendarterectomy for chronic thromboembolic pulmonary hypertension
      using circulatory arrest with selective antegrade cerebral perfusion.
AB  - The use of circulatory arrest with selective antegrade cerebral perfusion is
      described in a 59-year-old man who underwent thrombendarterectomy for chronic
      thromboembolic pulmonary hypertension. The postoperative course was uneventful.
      The described surgical technique may prevent the patient from cerebral sequelae
      especially in more complex cases.

PMID- 9615167
TI  - Acute cardiac herniation following intrapericardial pneumonectomy.
AB  - Cardiac herniation is a rare but potentially fatal complication of
      intrapericardial pneumonectomy. It usually occurs within the first 24 hours
      postoperatively. Symptoms are side-related. It has a sudden onset and invariably
      evolves to cardio-vascular collapse. Clinical suspicion combined with plain chest
      X-ray and electrocardiographic changes must lead to a quick diagnosis. Definitive
      treatment requires prompt surgical action. Closure of the pericardial defect
      during initial operation does not exclude the possibility of cardiac herniation.
      We present a patient with a right-sided cardiac herniation after intrapericardial
      pneumonectomy. Patient was treated surgically and survived.

PMID- 9615168
TI  - Electrostatic contributions to molecular free energies in solution.

PMID- 9615169
TI  - Site-specific analysis of mutational effects in proteins.

PMID- 9615170
TI  - Allosteric transitions of the acetylcholine receptor.

PMID- 9615171
TI  - Deciphering the molecular code of hemoglobin allostery.

PMID- 9615172
TI  - Statistical thermodynamic linkage between conformational and binding equilibria.

PMID- 9615173
TI  - Analysis of effects of salts and uncharged solutes on protein and nucleic acid
      equilibria and processes: a practical guide to recognizing and interpreting
      polyelectrolyte effects, Hofmeister effects, and osmotic effects of salts.

PMID- 9615174
TI  - Control of protein stability and reactions by weakly interacting cosolvents: the
      simplicity of the complicated.

PMID- 9615175
TI  - A reliable procedure for differential staining of in vitro produced bovine
      blastocysts: comparison of tissue culture medium 199 and Menezo's B2 medium.
AB  - A reliable double-dye technique has been established for counting the number of
      inner cell mass and trophectoderm cells of in vitro produced bovine blastocysts.
      The latter were first incubated in a 1:2 dilution of a rabbit antiserum raised
      against a mixture of recombinant bovine interferon tau and serum containing
      medium conditioned by in vitro produced trophoblastic vesicles for 45 min at 39
      degrees C. Subsequently, the blastocysts were incubated in a 5% (v/v) solution of
      guinea pig complement in phosphate-buffered saline containing 50 micrograms/ml
      propidium iodide for 45 min at 39 degrees C. Then the blastocysts were
      transferred to ice-cold absolute ethanol containing 25 micrograms/ml bisbenzimide
      and evaluated under a fluorescence microscope. Since trophectoderm cells were
      permeabilised by antibody-mediated complement lysis, they were stained by
      propidium iodide (red or pink). Bisbenzimide can enter lysed and non-lysed cells
      and therefore stained also inner cell mass cells (blue) which had been protected
      from complement lysis by trophectoderm cells. This modified procedure proved to
      be very reliable for differential cell staining of bovine blastocysts produced
      under various culture conditions. A comparison of blastocysts produced in
      Menezo's B2 vs. TCM 199 media (both supplemented with 10% serum from cows at
      oestrus) revealed significant (P < 0.01) differences in total cell numbers (119
      +/- 24 vs. 84 +/- 10; mean +/- SD) and in the numbers of trophectoderm cells (79
      +/- 19 vs. 57 +/- 8) and inner cells mass cells (40 +/- 7 vs. 26 +/- 5) between
      the two culture systems. The modified staining procedure presented here is a
      valuable tool for evaluating the quality of in vitro produced bovine blastocysts
      and for improving of culture conditions.

PMID- 9615176
TI  - Treatment with progesterone and 17 beta-oestradiol to induce emergence of a newly
      recruited dominant ovulatory follicle during oestrus synchronisation with long
      term use of norgestomet in Brahman heifers.
AB  - The aim of this study was to determine the effect on ovarian follicular growth
      and atresia, of acute treatment with either 100 mg of progesterone (n = 10), 200
      mg of progesterone (n = 10), 10 mg of oestradiol + 100 mg of progesterone (n =
      10), 10 mg of oestradiol (n = 10) or no treatment (n = 10), given on Day 10 of a
      17-day treatment with a norgestomet implant in randomly cycling Bos indicus
      heifers. The fate of the dominant follicle on Day 10, emergence of the new cohort
      of follicles and the intervals from implant removal to ovulation were recorded by
      ultrasonography. Plasma concentrations of Luteinizing hormone (LH), progesterone
      and oestradiol were determined during the time when the norgestomet implant was
      in place. All treatments resulted in the emergence of a new cohort of follicles
      within 5 days of administration. The day of emergence of the ovulatory follicle
      tended to be delayed after treatment with 100 mg of progesterone (2.7 +/- 0.3
      days after treatment), 200 mg of progesterone (3.7 +/- 0.5 days after treatment),
      10 mg of oestradiol + 100 mg of progesterone (4.4 +/- 0.2 days after treatment)
      and 10 mg of oestradiol (4.6 +/- 0.4 days after treatment) compared to control
      heifers (1.4 +/- 1.4 days after time of treatment). The mean interval from
      implant removal to onset of oestrus was significantly shorter after treatment
      with 100 mg of progesterone (38.4 +/- 2.6 h) than after treatment with 200 mg of
      progesterone (61.5 +/- 3.9 h) but otherwise, the mean interval from implant
      removal to onset of oestrus did not differ. Oestrus synchrony, measured by the
      sample standard deviation of oestrus onset, was tighter in all treatment groups
      compared to untreated control heifers. The mean interval from implant removal to
      ovulation did not differ significantly between groups. The synchrony of
      ovulation, measured by the sample standard deviation of the interval from implant
      removal to ovulation, was significantly tighter after treatment with 100 mg of
      progesterone, 200 mg of progesterone and 10 mg of oestradiol compared to control
      heifers. Treatment with 10 mg of oestradiol resulted in ovulation in seven of 10
      heifers before implant removal, three of which failed to ovulate after implant
      removal. Progesterone administered on Day 10 lowered plasma LH concentrations (P
      < 0.05), whereas treatment with oestradiol caused a surge of LH and ovulation.
      Progesterone administered with oestradiol prevented the LH surge. A combination
      treatment of oestradiol and progesterone given on Day 10 of a 17-day norgestomet
      treatment in a range of follicular states resulted in the consistent emergence of
      a new cohort of follicles which included the eventual ovulatory follicle.

PMID- 9615177
TI  - Developmental capacity of bovine oocytes matured in two kinds of follicular fluid
      and fertilized in vitro.
AB  - This study was conducted to assess the ability of the follicular fluid derived
      from large and small follicles to support the in vitro oocyte maturation and
      subsequent fertilization and developmental capacity. Oocytes were cultured in
      bovine follicular fluid aspirated from small (SFF; 2-5 mm in diameter), large
      (LFF; 10 to 20 mm in diameter) follicles and TCM199 as a control under 5% CO2 in
      air. All maturation media were supplemented with 1 IU ml-1 pregnant mare serum
      gonadotropin. After 24 h culture, oocytes were fertilized in vitro with frozen
      thawed and heparin-treated (10 micrograms ml-1, 15 min) bull spermatozoa and
      cultured in TCM199 with bovine oviductal epithelial cells (BOEC) for 7 days.
      Maturation of bovine oocytes cultured in LFF was inhibited and the low of male
      pronucleus formation was observed when compared with that of SFF (maturation
      rate: 69 vs. 78%; P < 0.05; male pronucleus formation rate: 58 vs. 80%; P <
      0.05). Developmental capacity of bovine oocytes cultured in SFF was significantly
      (P < 0.05) higher than that of LFF (15 vs. 5%), but significantly (P < 0.05)
      lower than that of the control. There were no differences in the number of nuclei
      per blastocyst obtained after each treatment. These results indicate that the
      inhibitory action of follicular fluid on in vitro maturation, male pronucleus
      formation and developmental capacity of bovine oocytes is dependent on the
      developmental stage of the follicles from which fluid was obtained.

PMID- 9615178
TI  - The effect on luteolysis by intensive oral administration of flunixin granules in
      heifers.
AB  - The objective of the study was to investigate whether oral administration of
      flunixin meglumine (FM) in the form of granules could prolong the functional life
      of the corpus luteum in heifers. Previous studies have shown that intensive, i.e.
      four times daily parental administration of FM can postpone luteolysis. Twelve
      heifers received an oral dose of 2.2 mg flunixin per kg body weight. Three dosing
      regimes were used; twice (n = 2), thrice (n = 4) and four times daily (n = 6).
      The 9-day-treatment period started on Day 14/15 of the oestrous cycle. Blood
      samples were collected twice daily during the entire experimental period.
      Frequent samples were withdrawn from Day 14/15 for 10 and 15 days in the control
      and treatment oestrous cycles, respectively, at 0600, 0800, 1000, 1200, 1400,
      1600, 1800 and at 2000 h. The plasma was analysed for the content of the main
      metabolite of PGF2 alpha, i.e. 15-ketodihydro-PGF2 alpha, and progesterone. A
      control cycle preceded the treatment cycle so that each heifer acted as its own
      control. The length of the oestrous cycle was significantly increased when FM was
      administered thrice, from 18-22 days to 20-24 days (P < 0.05), and four times
      daily, from 18-21 days to 25-27 days (P < 0.01), but not in the twice daily
      dosing regime (one-way ANOVA). When FM was administered twice and thrice,
      luteolysis occurred during treatment. However, when the four times daily regime
      was used, luteolysis was obtained when the treatment had terminated. No changes
      in progesterone levels were recorded, although the luteal phase increased when
      the oestrous cycle length was prolonged. The number of PG-pulses decreased
      significantly, from 6-12 pulses to 0-3 pulses (P < 0.01), when FM was
      administered four times daily. A reduction was also observed when heifers
      received the drug thrice, but the decrease was not significant. The oral route of
      administration was found to be as effective as the parental one to affect the
      mechanism responsible for luteolysis in heifers. However, to inhibit and postpone
      luteolysis, administration of FM four times daily is a necessity. Our results
      show that oral administration of FM in the bovine species can be of value both in
      research as well as in the clinic, e.g. to support the luteal function.

PMID- 9615179
TI  - Effects of insulin-like growth factor-1 on luteinizing hormone secretion in
      sheep.
AB  - Circulating insulin-like growth factor-1 (IGF-1) may be involved in nutritional
      modulation of reproductive status. Acute effects of IGF-1 on luteinizing hormone
      (LH) secretion were studied in two experiments, each using eight castrate male
      sheep surgically prepared with an elevated carotid artery, four with (E+) and
      four without (E-) subcutaneous oestradiol implants. Blood samples were taken
      every 12 min for 8 h at weekly intervals, with IGF-1 given at 4 h. In Experiment
      1, sheep were fed to maintain live weight (maintenance) and IGF-1 doses tested
      were 25, 50, 100 and 150 micrograms kg-1 given via the carotid (i.c.). Plasma LH
      concentrations were 6.2 +/- 0.35 (E-) and 4.2 +/- 0.49 (E+) ng ml-1 pre-IGF-1,
      were increased after 25 micrograms kg-1 IGF-1 (E-, 15%; E+, 11%) but were either
      unaltered (E-) or decreased (E+, -16%) after 150 micrograms kg-1; thus, mean LH
      response was negatively related to IGF-1 dose (E-, b = -0.007, P < 0.01; E+, b = 
      0.011, P < 0.05). LH pulse frequencies (p.f.) were 4.6 +/- 0.42 (E-) and 3.9 +/-
      0.35 (E+) pulses per 4 h pre-IGF-1, were unaltered after 25 micrograms kg-1 IGF
      1, but were decreased after 150 micrograms kg-1 (E-, -33%; E+, -51%); thus, p.f.
      was also negatively related to IGF-1 dose (E-, b = -0.016, P < 0.01; E+, b = 
      0.019, P > 0.05). LH pulse amplitude and baseline were not significantly altered
      by IGF-1. Plasma glucose concentrations decreased after 100 and 150 micrograms kg
      1 IGF-1 from 3.40 to 2.50 and 2.34 mmol l-1, respectively (SED 0.314, P < 0.001),
      but were not significantly altered after lower doses. Thus, hypoglycaemia caused
      LH inhibition after higher doses of IGF-1, which counteracted (E-) or overcame
      (E+) the stimulatory effects on LH seen after lower doses. In Experiment 2, sheep
      were fed 50% maintenance; saline vehicle i.c., then IGF-1 doses 25 and 50
      micrograms kg-1 given i.c. or i.v. were tested. In E- and E+ sheep, respectively,
      mean LH pre-IGF-1 was 8.7 +/- 0.97 and 1.9 +/- 0.16 ng ml-1, p.f. was 3.8 +/-
      0.44 and 0.8 +/- 0.44 pulses per 4 h, and amplitude was 3.6 +/- 0.49 and 0.4 +/-
      0.08 ng ml-1. Saline vehicle had no effect on LH. IGF-1 at both doses and by both
      administration routes in E- sheep increased mean LH (22-29%, P < 0.001), and in
      E+ sheep increased mean LH (12-36%, P < 0.001), p.f. (94-219%, P < 0.001) and
      amplitude (125-803%, P < 0.01). Thus, low doses of peripherally-administered IGF
      1 stimulated LH output in sheep, consistent with its putative physiological role
      as a nutritional modulator of reproduction.

PMID- 9615180
TI  - Elevation in tumour necrosis factor-alpha (TNF-alpha) messenger RNA levels in the
      uterus of pregnant gilts after oestrogen treatment.
AB  - In pigs, induction of embryonic degeneration, by exogenous oestrogens given early
      in gestation, has been long recognised. However, the underlying mechanisms
      responsible for this degeneration remain unclear. The present study was conducted
      to determine whether oestrogen-induced early porcine embryonic mortality was
      associated with changes in the levels of tumour necrosis factor-alpha (TNF-alpha)
      messenger RNA in the uterine endometrium. Prepubertal gilts were induced into
      oestrus with PG600 and artificially inseminated at their second natural oestrus
      and again 24 h later. After insemination, gilts were randomly assigned to
      treatment and given 0.5 ml intramuscular injections of either oestradiol valerate
      (10 mg ml-1) or corn oil on day 9 and 10 of gestation. The gilts were slaughtered
      on day 12, 15 or 18 of gestation. The reproductive tract was removed from each
      gilt and the uterine horns were flushed to check for the presence and integrity
      of embryos. Samples of uterine endometrial tissues were collected, snap-frozen in
      liquid nitrogen and stored at -80 degrees C. Total cellular RNA was isolated from
      frozen tissues using a guanidine isothiocyanate-cesium chloride method. The
      abundance of TNF-alpha messenger RNA was determined by Northern blot
      hybridisation analysis. Treatment of pregnant gilts with oestrogen resulted in
      severe fragmentation of embryos on days 15 (2/3) and 18 (2/2), confirming the
      embryocidal effect of exogenous oestrogen. Uterine TNF-alpha messenger RNA level
      was elevated in oestrogen-treated gilts compared with controls (P < 0.05). This
      observation of an association between increased levels of TNF-alpha mRNA in the
      uterus and embryonic degeneration in oestrogen-treated gilts suggests that TNF
      alpha may be involved in mediating oestrogen-induced early embryonic mortality in
      the pig.

PMID- 9615181
TI  - Effects of treating young boars with a GnRH depot formulation on endocrine
      functions, testis size, boar taint, carcass composition and muscular structure.
AB  - A study was designed to determine the effects of triptorelin (Decapeptyl C.R.), a
      GnRH-agonist in a depot formulation, on androst-16-en-3-one (androstenone), LH,
      oestradiol and testosterone and on carcass composition and muscle structure in
      boars. Treatment with this highly potent GnRH analog ensured peptide release for
      4 weeks when given to 18 animals at 135 days of age (group 1). Control animals (n
      = 20, group 2) received a saline injection. Blood samples (n = 10) were collected
      by venipuncture from each boar from 7 days before hormone treatment to 28 days
      after treatment. During the treatment period, three samples of back fat were
      taken by biopsy to determine the levels of androstenone and skatole. Testis size
      was determined at slaughter at 165 days of age. The treatment of boars with
      triptorelin increased concentrations of LH, oestradiol-17 beta, and testosterone
      for one day, followed by a decrease to base-line concentrations. The result of
      sensorial testing for boar taint detection at slaughter showed a slight reduction
      in this trait (0.76 vs. 0.99). The concentration of androstenone in the body fat
      of all treated animals was lower than the generally accepted limit of 0.5
      microgram/g for the absence of boar taint, compared with the concentrations from
      20 control animals among which 13 showed levels higher than this limit. The
      hormonal treatment significantly reduced the weight and size of the tests. There
      was no effect on skatole levels in backfat (0.141 vs. 0.150 microgram/g). The
      GnRH-agonist did not influence the carcass composition of treated boars. The
      muscle meat percentage was not significantly altered in the experimental group
      (51.39 vs. 50.50%). Overall, these results indicate that the use of this form of
      GnRH-agonist in a depot formulation offers a new possibility for reducing
      concentrations of androstenone which is mainly responsible for undesirable boar
      taint.

PMID- 9615182
TI  - Effects of 6-N-propyl-2-thiouracil on growth, hormonal profiles, carcass and
      reproductive traits of boars.
AB  - Neonatal 6-N-propyl-2-thiouracil (PTU)-induced hypothyroidism reduces body weight
      but increases testicular size in adult male rodents. The objective of this study
      was to determine the effect of prepubertal PTU treatment on boars. For Experiment
      I, boars (n = 28) were randomly allotted to eight pens. Each pen received one of
      four PTU doses (0, 0.01, 0.03 and 0.1% in a basal diet) between 28 and 56 days of
      age (DOA). Due to a lack of difference among three PTU treatments, PTU-treated
      boars were pooled. Boars treated with PTU had lower (P < 0.05) ADG during
      treatment, lighter (P < 0.05) BW after 56 DOA and less (P < 0.05) developed
      epididymides at 154 DOA. For Experiment II, boars (n = 19) were randomly allotted
      to six pens. Each pen received one of three PTU treatments orally as: control
      (carrier), PTU-I (0.002% BW of PTU daily between 7 and 70 DOA), or PTU-II (0.002%
      BW of PTU daily between 28 and 91 DOA). During treatment, PTU-treated boars had
      lower (P < 0.05) serum T4 levels, rectal temperature, feed intake and ADG. Boars
      treated with PTU had lower (P < 0.05) BW between 63 and 154 DOA but higher (P <
      0.05) gain/feed between 105 and 133 DOA. Boars treated with PTU had less (P <
      0.05) developed epididymides and sperm count per gram testis at 238 DOA. These
      results suggest that prepubertal PTU-induced hypothyroidism had significant
      effects on growth, hormonal profiles, and reproductive traits of boars; however,
      it does not appear to be an effective method for increasing testis size and sperm
      production of commercial boars.

PMID- 9615183
TI  - Investigation of the relationship between farrowing environment, sex steroid
      concentrations and maternal aggression in gilts.
AB  - Maternal oestrogen and progesterone have been shown to be important in the
      initiation of maternal behaviour. Thirty-three Large White x Landrace gilts,
      housed in groups during pregnancy, were observed and aggressive interactions
      recorded. Individuals had jugular catheters implanted 14.5 (s.e. 0.34) days
      before their expected parturition date (EPD). Five days before EPD gilts were
      randomly allocated and moved to either a conventional farrowing crate (C; without
      straw, 16 gilts) or a pen (P; 2.1 x 3.1 m2; with straw bedding, 17 gilts). Blood
      samples were taken at frequencies determined by the proximity to farrowing onset.
      Piglets were removed at birth and returned 2 h after placental expulsion. The
      reaction of each gilt to her piglets was monitored. Gilts savaging piglets were
      sedated with azaperone (n = 8). There was no overall effect of farrowing
      environment on oestradiol and progesterone concentrations. The pre-farrowing
      ratio of progesterone to oestradiol was higher for (P) gilts (0.45 vs. 0.25, (P)
      vs. (C); S.E.D. 0.085, P < 0.05) as was their overall maximum oestradiol level
      (3.39 vs. 2.29 ng/ml, (P) vs. (C); S.E.D. 0.39, P < 0.01). In contrast to
      progesterone, oestradiol patterns varied considerably between individuals.
      Dominance rank value during pregnancy, but not levels of aggression, correlated
      positively to pre-farrowing oestradiol concentrations. Treatment with azaperone
      was not related to farrowing environment, piglet weight or litter size. Azaperone
      treated gilts showed a higher pre-farrowing oestradiol to progesterone ratio
      (0.55 vs. 0.29, +/- azaperone; S.E.D. 0.10, P < 0.05), significantly higher
      levels of oestradiol post-partum (0.7 vs. 0.19 ng/ml, +/- azaperone; S.E.D. 0.20,
      P < 0.001) and significantly lower levels of aggression during pregnancy (1.68
      vs. 2.23 aggressive interactions/h, +/- azaperone; S.E.D. 0.15, P < 0.001). The
      results indicate that there are no major effects of farrowing environment on sex
      steroid concentrations. Maternal aggression under these conditions appears to be
      negatively related to aggression during pregnancy, but this is not reflected in
      plasma concentrations of sex steroids around parturition.

PMID- 9615184
TI  - Plasma concentrations of 15-ketodihydro-PGF2 alpha, progesterone, oestrone
      sulphate, oestradiol-17 beta and cortisol during late gestation, parturition and
      the early post partum period in llamas and alpacas.
AB  - Plasma concentrations of 15-ketodihydroprostaglandin (PG) F2 alpha, progesterone,
      oestrone sulphate, oestradiol-17 beta and cortisol during late gestation,
      parturition and the early post-partum period were measured in six llamas and five
      alpacas. During the last 100 days of pregnancy, 15-ketodihydro-PGF2 alpha
      concentrations increased steadily until the day of parturition when a massive
      release was detected (P < 0.01) concomitant with a decrease in progesterone
      concentrations (P < 0.01). The highest PGF2 alpha metabolite concentrations (159
      +/- 35 nmol l-1 and 92 +/- 29 nmol l-1 in llamas and alpacas respectively) were
      detected in the sample collected during the morning on the day of parturition.
      Basal concentrations were registered by day 3 after delivery. Plasma
      concentrations of oestrone sulphate started to increase 80 days before
      parturition and reached peak concentrations immediately before parturition (15 +/
      3 nmol l-1 in llamas and 18 +/- 5 nmol l-1 in alpacas). Oestrone sulphate
      concentrations dropped sharply (P < 0.01) on the day of parturition in llamas and
      one day later in alpacas, whereupon they remained relatively unchanged until at
      least 20 days postpartum. Oestradiol-17 beta concentrations were higher than 180
      pmol l-1 during the last 45 days of pregnancy, began to decrease on the day of
      parturition and reached very low concentrations within the following two days.
      High oestradiol-17 beta concentrations were registered 7 days postpartum in all
      alpacas (P < 0.05) and within 10 days of parturition in five of six llamas (P <
      0.01). No significant cortisol peaks were observed around parturition, but mean
      concentrations were increased in both species.

PMID- 9615185
TI  - The canine oocyte penetration assay; its use as an indicator of dog spermatozoal
      performance in vitro.
AB  - In vitro maturation and fertilisation has yet to be thoroughly investigated in
      the dog and is work that is required before gamete salvage programmes can be
      established in endangered canine species. Due to the differences which exist
      between the reproductive function of Canidae and other domestic species, in vitro
      requirements of both the oocyte and spermatozoa may also differ, and these remain
      to be established. The objective of this study was to investigate the ability of
      in vitro capacitated canine spermatozoa to penetrate the zona pellucida of in
      vitro matured canine oocytes. Two methods, one which utilised the fluorescent
      nuclear label Hoechst 33258 in combination with an aceto-orcein stain with light
      microscopy, and another using the fluorescence microscopy method alone were
      effective for staining both oocyte nuclear material and penetrated spermatozoal
      heads. These techniques only rarely allowed identification of both in the same
      oocyte. Using this assay, two to capacitate and acrosome react in vitro as
      measured by the chlortetracycline and Hoechst 33258 dual fluorescence staining
      method. No correlation however was found between acrosomal status of spermatozoa
      and spermatozoal penetration of homologous oocytes, although some relationship
      was observed. In addition, it was found that the effect of the stage of oocyte
      nuclear maturation had no effect upon spermatozoal penetration and that immature
      oocytes could be penetrated by spermatozoa in this species.

PMID- 9615186
TI  - The seriously burned child: resuscitation through reintegration--2.

PMID- 9615187
TI  - Nuclear transport factors: function, behavior and interaction.

PMID- 9615188
TI  - Steroid hormones modify nuclear heterochromatin structure and plasma membrane
      enzyme of MCF-7 cells. A combined fractal, electron microscopical and enzymatic
      analysis.
AB  - Ultrastructural features of the nuclear membrane envelope (ENM) and the nuclear
      membrane-bound heterochromatin (NMBHC) were investigated in MCF-7 human breast
      cancer cells by fractal morphometry. The fractal dimension D established by the
      box counting method proved to be effective for quantifying nuclear changes in MCF
      7 cells treated with steroid hormones, namely the estrogen 17 beta-estradiol,
      which stimulates cell proliferation, and the glucocorticoid dexamethasone. When
      MCF-7 cells were briefly (5 min) cultured in the presence of 17 beta-estradiol
      (10(-9) M), the irregularity of the NMBHC outline was increased as documented by
      the increased fractal dimension D. Changes in the ultrastructural complexity of
      the nuclear heterochromatin were observed in concomitance with functional changes
      at the cell periphery, namely the modulation of the estrogen-induced activity of
      phospholipase C, a cell membrane-associated enzyme involved in the signal
      transduction pathway via phosphoinositides metabolism. Dexamethasone did not
      affect the in vitro proliferation, the phospholipase C activity nor the shape of
      the ENM of MCF-7 cells, but reduced the structural complexity of the nuclear
      membrane-bound heterochromatin.

PMID- 9615189
TI  - Detection of CD5 antigen on B cell lymphomas in fixed, paraffin embedded tissues
      using signal amplification by catalyzed reporter deposition.
AB  - CD5 surface antigen is expressed on some categories of B cell lymphomas. The
      detection of CD5 coexpression on malignant B cell infiltrates, particularly in
      small biopsy specimens, is useful in distinguishing between small lymphocytic
      lymphoma, mantle cell lymphoma, low grade marginal zone B cell lymphoma, and
      follicular small cleaved cell lymphoma. However, conflicting results have been
      reported with regard to the detection of CD5 antigen expression on B cell non
      Hodgkin's lymphomas (B-NHLs) in fixed, paraffin embedded tissues using routine
      immunohistochemical (IHC) staining techniques. We used catalyzed reporter
      deposition (CARD) as a strategy to amplify the IHC signal and consequently
      increase the sensitivity of antigen detection. CARD improved detection of CD5
      antigen without sacrificing specificity of the test. In our study, virtually all
      malignant B-NHLs with CD5 antigen expression showed strong immunoreactivity for a
      commercially available anti-CD5 monoclonal antibody using CARD, whereas the
      majority of the same lymphomas did not label for CD5 using routine IHC without
      CARD amplification. The concordance between CD5 antigen detection by
      immunophenotyping of fresh or frozen tissues and immunostaining with CARD
      amplification on paraffin fixed tissue sections was 100%. It appears that this
      method can be applied in the diagnostic evaluation of B-NHLs or in other
      situations that a weak antigen signal is present.

PMID- 9615190
TI  - Immunohistochemical detection of cell-cycle associated markers on paraffin
      embedded and formalin fixed needle biopsies of prostate cancer: correlation of
      p120 protein expression with AgNOR, PCNA/cyclin, Ki-67/MIB1 proliferation-scores
      and Gleason gradings.
AB  - Paraffin embedded and formalin fixed needle biopsies of prostate cancer (PC) were
      used to immunocytochemically detect the p120 nucleolar protein in relation to the
      Gleason histological gradings (GHG), the labelling indices of proliferating
      nuclear immunocytochemical markers (PCNA/Cyclin, Ki-67/MIB1) and the argyrophilic
      nucleolar region (AgNOR) rate. The twenty-six cases of PC (6 from large
      histological samples and 20 from needle biopsies) were equally distributed into
      low (< or = 6) or high (> or = 7) GHG groups. The p120 nucleolar protein
      immunocytochemical reaction was randomly expressed in large histological sections
      but uniformly distributed without gaps in needle biopsy sections. Only on the
      latter were quantitative values of PCNA/Cyclin (23.2 in low and 45.3 in high
      GHG), Ki-67/MIB1 (13.8 in low and 43.3 in high GHG) and AgNOR (5.0 in low and 7.5
      in high GHG) related to those of p120 nucleolar protein (0.8 in low and 3.8 in
      high GHG). The values of all these cell cycle markers increased from low to high
      GHG of PC, all four reaching high statistical significance between the two groups
      (ANOVA-two tailed p < 0.0001). The PCNA/Cyclin index showed a higher positivity
      than the Ki-67/MIB1 index in PC with low GHG but not in PC with high GHG. In
      conclusion, paraffin embedded and formalin fixed PC needle biopsies exhibit a
      higher diagnostic PCNA/Cyclin than Ki-67/MIB1 index for cases presenting
      differentiated features, whereas p120 nucleolar protein detection seems to be a
      suitable marker of poorer outcome of PC.

PMID- 9615191
TI  - Objectivity of two methods of differentiating fibre types and repeatability of
      measurements by application of the TEMA image analysis system.
AB  - The objectivity of two of the most widely used methods for differentiation of
      fibre types, i.e. 1) the myosin ATP-ase method (Brooke and Kaiser, 1970a,b) and
      2) the combined method, by which the myosin ATP-ase reaction is used to
      differentiate between fast and slow twitch fibres and NADH-tetrazolium reductase
      activity is used to identify the subgroups of fast twitch fibres (Ashmore and
      Doerr, 1970, Peter et al., 1972), was assessed in muscle samples from horses,
      calves and pigs. We also assessed the objectivity of the alpha-amylase-PAS
      preparation for the visualisation of capillaries (Andersen, 1975) in these
      species. For the purpose of reducing the time costs of histochemical analysis of
      muscle samples, we have developed an interactive image analysis system which is
      described. All analyses are performed on this system. In accordance with several
      other investigations, differences between the two methods of differentiating
      fibre types were found only for the relative distribution of the fast-twitch
      fibre subgroups (p < 0.02 and p < 0.05 for the relative number of type IIA and
      IIB, respectively) whereas when calculated in relative area, only the proportion
      of type IIA fibres differed significantly (p < 0.05). Significant interaction
      effects between method and person and method and species were found for the same
      traits. When methods were analysed separately, the combined method displayed a
      significant variance component of person for the distribution of type IIA fibres
      both in relative number and in relative area (p < 0.01 and p < 0.001,
      respectively). The objectivity of the ATP-ase method was further substantiated by
      the fact that a higher fraction of the total variance for the relative area
      distribution of type IIA fibres was explained by the statistical model (72.1%
      versus 34.2% for the combined method). Although the repeatability of measurements
      between persons was generally high (> 87%), the impact of differences in pre
      requisites (varied degrees of overlap between the fibre types) for performing the
      differentiation by the combined method raises a question of the reliability of
      this method. Apparently, no general rules for comparison of results of
      distribution of the two subgroups of fast twitch fibres by the two methods are
      applicable. The alpha-amylase-PAS method was found to be a fairly objective
      method to identify capillaries in muscles from horses, calves and pigs. However,
      as capillarity described in combination with other traits to give an indication
      of diffusion characteristics is significantly influenced by person, it is
      recommended that the same person perform all the analysis of a project. In
      addition to the methodological results in this study, we have shown that by
      application of the TEMA image analysis system, which is more rapid compared with
      the time-consuming traditional method for evaluation of histochemical
      preparations, analysis of samples from large-scale experiments are now possible.

PMID- 9615192
TI  - Lectin-binding sites in uterus and oviduct of normal and Campylobacter fetus
      subspecies venerealis-infected heifers.
AB  - This study was carried out to investigate the effect of infection with
      Campylobacter fetus subsp. venerealis (Cfv) on the pattern of lectin binding in
      the uterus and oviduct of heifers. Cfv persistence was demonstrated by bacterial
      isolation and immunofluorescence. Infected animals showed variations in the
      lectin binding pattern when compared with control animals. Cfv-infected heifers
      showed an increased expression of galactose and N-acetyl-galactosamine in the
      endometrial glands (PNA and SBA binding, respectively). The oviductal epithelium
      of infected heifers was strongly positive for Con A, which indicated the presence
      of alpha-D-mannose and alpha-D-glucose. The results of this study showed that Cfv
      infection modifies the lectin binding pattern in the reproductive system of
      heifers. Modifications in glycoconjugates may be involved in failures of
      fertility and/or implantation.

PMID- 9615193
TI  - Changes in NADPH-diaphorase expression induced by excitotoxicity in the goldfish
      retina: relation with some morphological and biochemical aspects.
AB  - We report alterations in the pattern of NADPH-diaphorase staining, a marker of
      nitric oxide, in the goldfish retina after kainic acid administration. The
      heavily stained ellipsoids of the photoreceptors, the heavily stained neurons of
      the inner plexiform layer and the labeled neurons of the ganglion cell layer are
      spared by excitotoxic insult, while the faintly medium sized neurons of the inner
      plexiform layer disappear after kainic acid administration. Furthermore, in the
      bipolar and in the horizontal retinal neurons we observe an induction of NADPH
      diaphorase expression. The kainic acid-induced neurotoxicity evaluated by
      morphological observations and by measuring the levels of choline
      acetyltranferase in retinal homogenates, is not prevented by the administration
      of a nitric oxide synthase inhibitor.

PMID- 9615194
TI  - Immunohistochemical localization of FSH and LH in the pituitary of male ruin
      lizards (Podarcis sicula campestris De Betta).
AB  - The pars distalis from the pituitary gland of adult male ruin lizards (Podarcis
      sicula campestris De Betta), captured during the reproductive period (May and
      June), was studied immunohistochemically using specific antibodies against hFSH
      beta, hLH beta and oLH beta with the avidin-biotin-peroxidase complex (ABC)
      procedure to determine the localization of both gonadotropins. The immunostaining
      with anti-hFSH beta and anti-hLH beta allowed identification of morphologically
      distinct FSH containing cells and LH containing cells, whereas anti-oLH beta
      serum showed cross-reactivity with cells immunostained with the anti-hFSH beta
      and anti-hLH beta sera. The gonadotropic cells took up approximatively 10.5% of
      the area of the pars distalis: 10% was positive for FSH, whereas only 0.5% was
      positive for LH. The FSH cells were distributed throughout the pars distalis,
      whereas the LH cells were only located in the rostral region. Double
      immunostaining procedure did not reveal cells containing both gonadotropic
      hormones. The findings indicate that FSH and LH are produced in separate
      pituitary cells.

PMID- 9615195
TI  - Natural history and patterns of invasive cancer of the bladder.

PMID- 9615196
TI  - Phenotypic characterization of bladder cancer.

PMID- 9615197
TI  - DNA methylation in bladder cancer.

PMID- 9615198
TI  - Molecular cytogenetics of bladder cancer progression.

PMID- 9615199
TI  - Cell cycle regulators as prognostic factors for bladder cancer.

PMID- 9615200
TI  - Molecular prognostic factors in bladder cancer.

PMID- 9615201
TI  - Invasive bladder carcinoma: progress in basic research, surgical and medical
      therapy.

PMID- 9615202
TI  - T1 and T2 bladder cancer: selecting optimal therapy.

PMID- 9615204
TI  - Meticulous pelvic lymphadenectomy in surgical treatment of the invasive bladder
      cancer: an option or a must?

PMID- 9615203
TI  - Anterior exenteration with subsequent ureteroileal urethrostomy in females.
      Anatomy, risk of urethral recurrence, surgical technique, and results.

PMID- 9615205
TI  - Complications and results after cystectomy in male and female patients with
      locally invasive bladder cancer.

PMID- 9615206
TI  - 25-year experience in the management of invasive bladder cancer by radical
      cystectomy.

PMID- 9615207
TI  - Locally advanced bladder cancer. Radiation therapy and chemotherapy.

PMID- 9615208
TI  - An update of selective bladder preservation by combined modality therapy for
      invasive bladder cancer.

PMID- 9615209
TI  - Nordic prospective trials of radical cystectomy and neoadjuvant chemotherapy. The
      Nordic Cooperative Bladder Cancer Study Group.

PMID- 9615210
TI  - Population genetics of the D4S139, D10S28, D17S74 and D17S79 VNTR loci among
      Asian, black, Caucasian, Hispanic and Native American populations from Seattle.
AB  - We studied four variable number of tandem repeat (VNTR) loci (D4S139, D10S28,
      D17S74, and D17S79) in five ethnic populations from the Seattle metropolitan
      area. DNA samples purified from randomly chosen individuals were digested with
      Hae III or Hinf I and probed with pH30, for D4S139; TBQ7 for D10S28; pCMM86 for
      D17S74 and pAC256 for D17S79. The allele frequencies, expected Hardy-Weinberg
      values, observed heterozygosities and genetic distances among the populations
      were obtained for all these loci. D4S139 restriction fragment lengths (RFLs)
      varied in size from 1.4 to 22 kilobase pairs (kbp). The observed heterozygosities
      (H) varied from 84% in Native American populations to 94% among Blacks. D10S28
      RFLs varied in size from 650 base pairs (bp) to 10.1 kbp. H varied from 90% in
      Native Americans to 96% in Caucasians and Hispanics. D17S74 RFLs varied in size
      from 782 bp to 9.3 kbp. H varied from 87% in Asians to 92% among Blacks. D17S79
      RFLs varied in size from 400 bp to 3 kbp. H varied from 87% in Hispanics to 95%
      in the Black population. The frequencies of genotypes of the loci conformed to
      Hardy-Weinberg equilibrium with the exception of the D17S79 in Hispanics and
      Native Americans. The genetic distances between the populations were also
      determined.

PMID- 9615211
TI  - Seventy-five nuclear DNA polymorphisms in an Italian sample: a comparative
      worldwide study.
AB  - A well defined Italian sample from Trino Vercellese (Northern Italy) is analysed
      for 75 nuclear DNA RFLPs. It represents the only European sample [Matullo et al
      1994] which is unmixed in a comparative study of eight populations from four
      continents [Bowcock et al 1991a; Lin et al 1994]. Genetic substructure of this
      sample has been investigated by allele sharing distances and no bias or higher
      homogeneity is shown. Genetic variability between populations was measured by the
      FST statistics (average FST was 0.138 +/- 0.086). Average heterozygosity for
      eight populations was 0.312 +/- 0.069. Genetic distances were evaluated between
      pairs of populations. Phylogenetic trees were reconstructed and principal
      component analysis performed. Particular attention has been given to the genetic
      relationship between our sample and the mixed-Caucasoid sample: 14 out of 75
      markers show statistically significant frequency differences (P < 0.05), 5 of
      which are significant at a probability level < 1%: GH/Bg1II (Lower system),
      D7S1/HindIII, D17S71/MspI, EPB3/PstI, HLA-DQA. Hypotheses on admixed origin of
      Europeans has been discussed.

PMID- 9615212
TI  - Frequency of the blood group antigen K and the A1A2BO groups in the Norwegian
      counties.
AB  - Blood samples from 15,426 blood donors from 17 out of Norway's 19 counties were
      tested for the presence of Kell (k) antigen. The K+ frequency in the total series
      was 8.28%, ranging from 4.61% in East-Agder county to 10.36% in Sogn and
      Fjordane. A1A2BO grouping of the donors showed that the lowest frequencies of
      group O were found in southeastern Norway (the counties surrounding the Oslo
      Fjord), and the highest along the coast of western Norway and in Nordland county.
      The highest A2 blood group frequencies were found in the three counties of
      northern Norway, with a maximum value in Finnmark county. The ratio between the
      genes determining the A1 and A2 properties (the p1/p2 ratio) was highest in
      southern Norway where in most counties was above 3. All the counties along the
      coast from Sogn and Fjordane northwards to the northern end of the country gave
      p1/p2 ratio below 3 and, in Finnmark, it was slightly below 2.

PMID- 9615213
TI  - Preliminary estimation of the Y Alu polymorphic (YAP) element in the Romanian
      population.
AB  - We analyzed the polymorphism for the presence/absence of the YAP element in two
      male Romanian samples. Frequencies of 3.7% and 10.5% were found for the presence
      of the element in Maramures (North Romania) and Vrancea (East Romania).

PMID- 9615214
TI  - Distribution of 9 common mutations in the CFTR gene in Slovak cystic fibrosis
      patients.
AB  - The distribution of 9 known mutations in the CFTR gene were studied in 234 CF
      chromosomes originating from 117 unrelated cystic fibrosis (CF) patients from
      Slovakia, a population which is geographically situated at the borders between
      Western and Eastern Europe, and Northern and Southern Europe. The following 7
      mutations were identified in this sample: delta F508 (59.4%), G542X (5.56%),
      R553X (3.42%), N1303K (2.99%), R347P (1.71%), W1282X (0.85%), and 3849 + 10 kb
      (0.43%). These mutations represent 74.36% of all CF mutations, providing a good
      basis for direct DNA-based diagnosis of CF in Slovakia.

PMID- 9615215
TI  - A correction of the estimates of the least common cystic fibrosis (CF) mutations
      published by "The Cystic Fibrosis Genetic Analysis Consortium" in 1994.

PMID- 9615216
TI  - Study of a trimeric tandem repeat locus (SBMA) in the Basque population:
      comparison with other populations.
AB  - Microsatellites can be highly unstable and show a high level of polymorphism
      between individuals. Here we present the analysis of the CAG trinucleotide repeat
      polymorphism at the SBMA locus in 57 phenotypically normal individuals rigorously
      assigned to the Spanish Basque population. Results are compared with 100 Spanish
      non-Basque individuals who were already analyzed by us (175 alleles). This is the
      first study undertaken in these populations for this marker. In addition, we
      compared our results with those published for other populations. Relative allele
      frequencies showed differences between the samples and no unimodal distribution.
      The expected heterozygosity in the Basque sample was slightly lower than in the
      non-Basque sample. Conformity with Hardy-Weinberg equilibrium was verified by
      three tests. When compared with published data, the predominant alleles appear to
      be the same in the various populations. There are more differences between
      Basques and other Caucasoid samples than between non-Basques and Caucasoid
      samples. Population relationships were also examined by dendrograms based on
      genetic distances. The results obtained showed some peculiarities in the Basque
      population. The high degree of similarity with other dendrograms based on
      different markers and the efficiency of this STR marker in differentiating
      closely related populations, support the potential usefulness of microsatellites
      as tools for human population studies.

PMID- 9615217
TI  - Microheterogeneity and AMP-FLP analysis of the 3' flanking interleukin-6 VNTR
      polymorphism in central Spain.
AB  - The 3' flanking region of the interleukin-6 gene is polymorphic due to the
      existence of a hyper-variable region consisting of a number of A + T rich
      variable repeated DNA sequences (VNTR). We used specific primers to amplify this
      particular VNTR system by PCR in 222 unrelated normal Spaniards from Madrid,
      Spain. A model of inheritance comprising of five different allele classes was
      proposed and frequencies evaluated as follows: B4, 0.635; B3.1, 0.029; B3, 0.270;
      B2, 0.038; B1, 0.027. Also, examples of inheritance of mendelian
      microheterogeneity are shown. Heterozigosity index was calculated (H = 0.5) and
      no departure from Hardy-Weinberg equilibrium was observed (chi 2 = 0.091, d. f.
      1, p > 0.75).

PMID- 9615218
TI  - Dominant lethality of the mouse skeletal mutation tail-short (Ts) is determined
      by the Ts allele from mating partners.
AB  - Mice with the Tail-short (Ts) mutation have a short, kinky tail and numerous
      skeletal abnormalities, including a homeotic anteroposterior patterning problem
      involving the axial skeleton. The viability of Ts heterozygotes varies
      dramatically, depending on the mouse strain crossed with the mutant strain. At
      the extremes, the heterozygotes are viable or lethal prenatally. In this study,
      we found that laboratory mouse strains could be divided into two groups. A cross
      with strains from the first group yielded viable Ts heterozygotes, whereas a
      cross with the second group resulted in dominant lethality in utero. We planned
      to map the gene(s) that controls strain differences in the viability of the Ts
      heterozygotes. The result clearly indicated that a single chromosomal region,
      genetically inseparable from the Ts locus, is responsible for these differences.
      This suggests that allelism at the Ts locus generates variable manifestation of
      the mutant phenotype. Morphological and histological analyses indicated that
      embryos from the lethal cross exhibit severe developmental defects from the
      gastrulation stage through the early fetal stage. In particular, the umbilical
      vein does not develop properly. All of these results suggest that the phenotype
      of the Ts mutant is modified by the Ts alleles of the mating partners.

PMID- 9615219
TI  - A detailed physical and transcriptional map of the region of chromosome 20 that
      is deleted in myeloproliferative disorders and refinement of the common deleted
      region.
AB  - Acquired deletions of the long arm of chromosome 20 are the most common
      chromosomal abnormality seen in polycythemia vera and are also associated with
      other myeloid malignancies. Such deletions are believed to mark the site of one
      or more tumor suppressor genes, loss of which perturbs normal hematopoiesis. A
      common deleted region (CDR) has previously been identified on 20q. We have now
      constructed the most detailed physical map of this region to date--a YAC contig
      that encompasses the entire CDR and spans 23 cM (11 Mb). This contig contains 140
      DNA markers and 65 unique expressed sequences. Our data represent a first step
      toward a complete transcriptional map of the CDR. The high marker density within
      the physical map permitted two complementary approaches to reducing the size of
      the CDR. Microsatellite PCR refined the centromeric boundary of the CDR to
      D20S465 and was used to search for homozygous deletions in 28 patients using 32
      markers. No such deletions were detected. Genetic changes on the remaining
      chromosome 20 may therefore be too small to be detected or may occur in a
      subpopulation of cells.

PMID- 9615220
TI  - Tissue-specific expression and mapping of the Cox7ah gene in mouse.
AB  - We have isolated and examined the gene for the heart isoform of cytochrome c
      oxidase subunit VIIa (COX VIIa-H) in mouse, an isoform gene previously thought to
      be lacking in rodents. Interspecies amino acid comparisons indicate that mouse
      COX VIIa-H protein displays 82.5 and 70.9% identity with the bovine and human
      heart isoforms of COX VIIa, but only 53.7% identity with the paralogous mouse
      liver isoform (COX VIIa-L). Expression in adult mouse tissues is limited to heart
      and skeletal muscle, as found in other species. In the early mouse embryo, Cox7al
      was the exclusive isoform expressed and Cox7ah mRNA was not detectable until day
      17 postcoitum. That the mouse Cox7ah gene characterized in this study is
      orthologous to the human COX7AH gene was also suggested by its mapping to mouse
      chromosome 7, to a conserved region syntenic with the human chromosome location
      of COX7AH, 19q13.1. As a result, all three COX heart isoform genes in mouse group
      to chromosome 7. Interestingly, mapping of the mouse Cox7al to chromosome 9
      suggests a new syntenic region between the mouse and the human genomes.

PMID- 9615221
TI  - Physical and genetic maps of the deafwaddler region on distal mouse Chr 6.
AB  - The deafwaddler (dfw) mutation, displaying motor ataxia and profound deafness,
      arose spontaneously in a C3H/HeJ colony and was mapped previously to distal mouse
      Chr 6. In this study, a high-resolution genetic map was generated by positioning
      10 microsatellite markers and 5 known genes on a 968-meioses intersubspecific
      backcross segregating for dfw [(CAST/Ei(-)+/+ x C3HeB/ FeJ-dfw/dfw) x C3HeB/FeJ
      dfw/dfw], giving the following marker order and sex-averaged distances: D6Mit64
      (0.10 + 0.10 cM)-Pang-(1.24 + 0.36 cM)-Itpr1-(0.62 + 0.25 cM)-D6Mit108-(0.52 +
      0.23 cM)-D6Mit54-(0.21 + 0.15 cM)-D6Mit23, D6Mit107, D6Mit328-(0.72 + 0.27 cM)
      D6Mit11-(0.21 + 0.15 cM)-dfw-(0.93 + 0.31 cM)-Gat4, D6Mit55-(0.10 + 0.10 cM)
      D6Mit63-(0.31 + 0.18 cM)-Syn2-(0.62 + 0.25 cM)-D6Mit44 (Rho). Female and male
      genetic maps are similar immediately surrounding the dfw locus, but show marked
      differences in other areas. A yeast artificial chromosome-based physical map
      suggests that the closest markers flanking the dfw locus, D6Mit11 (proximal) and
      Gat4, D6Mit55 (distal), are contained within 650-950 kb. The human homologues of
      the flanking loci Itpr1 (proximal) and Syn2 (distal) map to chromosome 3p25-p26,
      suggesting that the human homologue of the dfw gene is located within this same
      region.

PMID- 9615222
TI  - The human HNRPD locus maps to 4q21 and encodes a highly conserved protein.
AB  - The hnRNP D protein interacts with nucleic acids both in vivo and in vitro. Like
      many other proteins that interact with RNA, it contains RBD (or "RRM") domains
      and arg-gly-gly (RGG) motifs. We have examined the organization and localization
      of the human and murine genes that encode the hnRNP D protein. Comparison of the
      predicted sequences of the hnRNP D proteins in human and mouse shows that they
      are 96.9% identical (98.9% similar). This very high level of conservation
      suggests a critical function for hnRNP D. Sequence analysis of the human HNRPD
      gene shows that the protein is encoded by eight exons and that two additional
      exons specify sequences in the 3' UTR. Use of two of the coding exons is
      determined by alternative splicing of the HNRPD mRNA. The human HNRPD gene maps
      to 4q21. The mouse Hnrpd gene maps to the F region of chromosome 3, which is
      syntenic with the human 4q21 region.

PMID- 9615223
TI  - Duplication of the DR3 gene on human chromosome 1p36 and its deletion in human
      neuroblastoma.
AB  - The human DR3 gene, whose product is also known as Wsl-1/APO-3/TRAMP/LARD,
      encodes a tumor necrosis factor-related receptor that is expressed primarily on
      the surface of thymocytes and lymphocytes. DR3 is capable of inducing both NF
      kappa B activation and apoptosis when overexpressed in mammalian cells, although
      its ligand has not yet been identified. We report here that the DR3 gene locus is
      tandemly duplicated on human chromosome band 1p36.2-p36.3 and that these genes
      are hemizygously deleted and/or translocated to another chromosome in
      neuroblastoma (NB) cell lines with amplified MYCN. Duplication of at least a
      portion of the DR3 gene, including the extracellular and transmembrane regions
      but not the cytoplasmic domain, was demonstrated by both fluorescence in situ
      hybridization and genomic Southern blotting. In most NB cell lines, both the DR3
      and the DR3L sequences are simultaneously deleted and/or translocated to another
      chromosome. Finally, DR3/ Wsl-1 protein expression is quite variable among these
      NB cell lines, with very low or undetectable levels in 7 of 17 NB cell lines.

PMID- 9615224
TI  - Cloning, genomic structure, and expression of mouse ring finger protein gene
      Znf179.
AB  - ZNF179, a RING finger protein encoding gene, has been mapped within the critical
      deletion region for Smith-Magenis syndrome (SMS), a disorder characterized by
      mental retardation and multiple congenital anomalies associated with
      del(17)(p11.2). Here we report the cloning of Znf179, the mouse homologue of
      ZNF179, and characterization of its gene structure. The 3028-bp cDNA has a 1.9-kb
      open reading frame that contains a RING finger domain at its N-terminus and an
      alanine-rich and glycine-rich domain at its C-terminus. Znf179 genomic sequence
      includes 15 introns and spans about 10 kb on mouse chromosome 11, which maintains
      conserved synteny with human 17p. Northern analysis indicates that Znf179 is
      predominantly expressed in brain and testis. Although contained within the SMS
      common deletion interval, FISH experiments show that ZNF179 is not deleted in two
      SMS patients with smaller deletions.

PMID- 9615225
TI  - Structure and transcription regulation of the human insulin-like growth factor
      binding protein 4 gene (IGFBP4).
AB  - Insulin-like growth factor binding protein 4 (IGFBP-4) is locally produced by
      normal human bone cells and acts as a potent inhibitor of IGF action in this
      tissue. PTH and a cAMP analog increase the expression of IGFBP4 mRNA in human
      osteoblast cells. We now show that the human IGFBP4 gene is contained within 15.3
      kb with the transcription initiation site located 28 bp downstream of a TATA box
      sequence and 286 bp upstream of the translation initiation codon. The 3'-end of
      the mRNA was identified at position 14281, but no conserved poly(A) addition
      signal was found within 30 bp upstream of this site. Deletion mutagenesis located
      the core promoter activity downstream of position -289, and the transcription
      activity disappeared at -6. Stimulation with 0.5 mM dibutyryl-cAMP resulted in a
      twofold increase of promoter activity. Elements responsible for the cAMP response
      reside between positions -869 and -6.

PMID- 9615226
TI  - An evolutionarily conserved gene on human chromosome 5q33-q34, UBH1, encodes a
      novel deubiquitinating enzyme.
AB  - While cloning breakpoint sequences of a leukemia patient exhibiting a t(5; 14)
      translocation, we identified a pseudogenic variant of a novel multigene family in
      proximity to the breakpoint. Chromosomal in situ hybridization suggested that the
      gene family is clustered on human chromosome 5q33-q34. The gene family is
      evolutionarily conserved. Northern blot analysis of mouse tissues revealed low
      level expression of a functional member of this gene family in almost all
      samples. Marked levels of transcripts were detected by in situ hybridization in
      the retina, the olfactory epithelium, the peripheral neuronal ganglia, and
      distinct areas of the gut. The predicted protein displays striking similarity to
      a hypothetical protein of Caenorhabditis elegans (R10E11.3.) and to two yeast
      deubiquitinating enzymes, Ubp9 and Ubp13, albeit to a lesser extent. We expressed
      the putative coding region of the human gene in Escherichia coli and demonstrated
      that it indeed bears deubiquitinating activity based on its ability to cleave
      ubiquitin from a ubiquitin-beta-galactosidase fusion protein. This new
      deubiquitinating enzyme has been named UBH1, for ubiquitin hydrolyzing enzyme 1.

PMID- 9615228
TI  - The mouse and rat MAP1B genes: genomic organization and alternative
      transcription.
AB  - We report the genomic organization of the mouse and rat genes coding for the 2460
      amino-acid microtubule-associated protein (MAP) 1B. In addition to seven exons
      that encode full-length MAP1B, we have identified two alternative exons, exon 3A
      and the novel exon 3U. We demonstrate that alternative MAP1B transcripts
      containing either exon 3A or exon 3U are expressed in a variety of mouse and rat
      tissues at about 1 to 10% of the level of regular transcripts. The alternative
      transcripts, if translated, would give rise to MAP1B isoforms truncated at the N
      terminus. The exon/intron organization underlying the alternative transcripts and
      the N-terminal amino acid sequence of the putative truncated MAP1B isoforms
      resemble those of MAP1A, providing further evidence for an evolutionary
      relationship. The detection of alternative transcripts has implications for the
      interpretation of conflicting results recently obtained in MAP1B knockout mice.

PMID- 9615227
TI  - Transcript mapping of the human chromosome 11q12-q13.1 gene-rich region
      identifies several newly described conserved genes.
AB  - Despite the localization of several human diseases to 11q13, the majority of the
      genes responsible for these disorders have not yet been cloned. Exon
      amplification and EST mapping were performed using clones derived from an
      approximately 1.65-Mb P1 artificial chromosome contig encompassing the region
      that reportedly harbors the gene mutated in the dominantly inherited eye
      disorder, Best disease. Fifty-eight exons isolated from the region were
      sequenced, resulting in 41.3% showing weak or no similarity to database
      sequences. Four exons had exact matches with human ESTs and 2 exons were highly
      similar to mouse ESTs. The sequence of 1 of these human ESTs was highly similar
      to that of the rat Rabin3 and mouse Pat-12 genes, which potentially encode Ras
      like GTPase binding proteins. Three exon sequences were similar to those of the
      inner centromere proteins of Gallus gallus and Xenopus laevis, which are mitotic
      phosphoproteins, and 1 exon sequence had similarity to the epidermal growth
      factor-like repeat from several proteins. High-resolution mapping of 34 ESTs
      binned to the 11q12-q13 region by the Human Transcript Mapping Project identified
      5 present in the PAC contig, with 1 of these ESTs identifying a human homologue
      of the rat synaptotagmin VII gene. Database searches identified two overlapping
      cDNA clones representing almost the entire open reading frame of this human gene
      and a sequenced cosmid indicating its partial genomic structure. Further database
      analyses identified another sequenced cosmid from this region that contained both
      exon-trap and mapped EST sequences. PowerBLAST and GRAIL analysis of this cosmid
      sequence identified matches with several other ESTs, the previously described
      FEN1 gene, and a novel evolutionarily conserved gene. These experiments identify
      candidate genes for disorders that map to this region and indicate that this is a
      gene-rich region of the human genome.

PMID- 9615229
TI  - Identification and molecular characterization of TM7SF2 in the FAUNA gene cluster
      on human chromosome 11q13.
AB  - In this report, the identification and molecular characterization of a novel
      gene, designated TM7SF2, is reported. This gene was found in the FAU neighboring
      area (FAUNA) to which other genes have been mapped previously. The FAUNA gene
      cluster is located at chromosome 11q13 between landmarks H4B and D11S2196E. The
      TM7SF2 gene contains eight coding exons, and their splice site consensus
      sequences are consistent with AG/GT rule. Northern blot analysis with a cDNA
      probe corresponding to TM7SF2 revealed varying expression levels of a 1.7-kb
      transcript in adult human heart, brain, pancreas, lung, liver, skeletal muscle,
      kidney, ovary, prostate, and testis, but no detectable expression in placenta,
      spleen, thymus, small intestine, colon (mucosal lining), or peripheral blood
      leukocytes. The open reading frame in the cDNA sequence codes for a protein of
      590 amino acids that is rich in glycine (23%) and arginine (17%) residues in its
      amino-terminal half and contains seven transmembrane domains in its carboxy
      terminal half. The transmembrane region of the putative TM7SF2 protein shows
      amino acid sequence similarity to those of the lamin B receptor and the C14/C24
      sterol reductase.

PMID- 9615231
TI  - GBAS, a novel gene encoding a protein with tyrosine phosphorylation sites and a
      transmembrane domain, is co-amplified with EGFR.
AB  - Amplification of the epidermal growth factor receptor gene (EGFR) has been noted
      in several forms of human cancer. Although various aspects of this gene
      alteration have been extensively studied, little is known about the genetic
      content of the chromosome 7p12 region that can be co-amplified with this cellular
      oncogene. Here we report the identification of and coding sequence for a novel
      gene, GBAS, that is localized to this region and was found to be amplified in 2
      of 12 tumors as well as in 2 of 3 cell lines with EGFR amplification. The GBAS
      transcript is 2.2 kb in length and contains an 858-bp open reading frame. The
      associated amino acid sequence has identifiable signal peptide and transmembrane
      motifs, as well as two tyrosine phosphorylation sites that suggest that the
      encoded protein may be a substrate for tyrosine kinases.

PMID- 9615230
TI  - Chromosomal mapping of Tmp (Emp1), Xmp (Emp2), and Ymp (Emp3), genes encoding
      membrane proteins related to Pmp22.
AB  - We have recently characterized a novel mammalian gene family, encoding membrane
      glycoproteins with four trans-membrane domains. This gene family includes the
      previously studied PMP22, which is involved in the Charcot-Marie-Tooth
      neuropathy, and three novel genes: TMP, XMP, and YMP (HGMW-approved symbols EMP1,
      EMP2 and EMP3, respectively). The Tmp (tumor-associated membrane protein) gene
      was isolated from a c-myc induced mouse brain tumor and is expressed in several
      highly proliferative cell types. We have now isolated cDNAs of the mouse Xmp and
      Ymp genes and determined the chromosomal localization of mouse Tmp, Xmp, and Ymp.
      Tmp was mapped to mouse chromosome 6, Xmp was mapped to chromosome 16, and Ymp
      was mapped to chromosome 7. Tmp and Ymp map to paralogous chromosomal regions,
      whereas Xmp maps to a chromosomal region that is putatively paralogous to a
      region on chromosome 11, to which Pmp22 was previously mapped. These data suggest
      that this family of membrane glycoproteins evolved as a result of chromosomal
      duplications.

PMID- 9615232
TI  - Expression and cytogenetic localization of the human SM22 gene (TAGLN).
AB  - SM22 is a 22-kDa protein identified variously as SM22, transgelin, WS3-10, or
      mouse p27. Though its precise function is unknown, it is abundant in smooth
      muscle and so may contribute to the physiology of this widespread tissue. We
      found that cosmid 16b6 contains the entire 5.4-kb, five-exon human SM22 gene
      (HGMW-approved symbol, TAGLN), and we cytogenetically localized the gene to
      chromosome 11q23.2. Northern analysis of human adult tissues showed that SM22
      mRNA is most prevalent in smooth muscle-containing tissues, but is also found at
      lower levels in heart. The human SM22 promoter contains nuclear factor-binding
      motifs known to regulate transcription in smooth muscle, and human SM22 promoter
      luciferase reporter constructs exhibited high transcriptional activity in A7r5 or
      primary canine aortic smooth muscle cells, but show little activity in nonmuscle
      COS7 cells. In addition, human SM22 promoter activity increased by two- to
      threefold upon serum stimulation of nonmuscle cells.

PMID- 9615233
TI  - Cloning, expression analysis, and chromosomal localization of BH-protocadherin
      (PCDH7), a novel member of the cadherin superfamily.
AB  - We have identified a novel member of the cadherin superfamily. Among the members
      of the superfamily, this protein exhibited the highest overall homology with
      protocadherin-1 (46-49% identity). Its mRNA was predominantly expressed in the
      brain and heart. Hence, we named the gene BH-protocadherin (BH-Pcdh) (HGMW
      approved symbol PCDH7). BH-Pcdh has an extracellular domain consisting of seven
      repeats of the cadherin motif (EC 1 to 7). EC2 of BH-Pcdh is unique in having a
      55-amino-acid insertion in the middle of the motif. There are three isoforms of
      BH-Pcdh, denoted -a, -b, and -c, which have different cytoplasmic tails and a 47
      amino-acid deletion in the EC2-3 region of BH-Pcdh-c. While only a 9.0-kb message
      was detected in normal tissues, 4.5- and 9.0-kb mRNA species were seen in the
      human lung carcinoma cell line A549. Furthermore, only the 4.5-kb mRNA was
      detected in HeLa cell S3 and human gastric cancer cell lines MKN28 and KATO-III.
      Southern blot analysis indicated that the BH-Pcdh gene is likely to be conserved
      among various vertebrates. The BH-Pcdh gene was localized to human chromosome
      4p15. Interestingly, 4p15 is a region of loss of heterozygosity in some head and
      neck squamous cell carcinomas.

PMID- 9615234
TI  - Structure of the human paralemmin gene (PALM), mapping to human chromosome
      19p13.3 and mouse chromosome 10, and exclusion of coding mutations in grizzled,
      mocha, jittery, and hesitant mice.
AB  - Paralemmin is a newly identified protein that is associated with the plasma
      membrane and with intracellular membranes through a lipid anchor. It is abundant
      in brain, is expressed at intermediate levels in the kidney and in endocrine
      cells, and occurs at low levels in many other tissues. As it is a candidate for
      genetic disorders that affect membrane functions, we have determined the
      structure of the human paralemmin gene, PALM, showing that it is organized into
      nine exons. Moreover, we have performed chromosomal assignments of the human and
      mouse paralemmin genes, localizing them to regions of homology at human 19p13.3
      and the central mouse chromosome 10. Finally, mutation analysis using RNA from
      mice homozygous for the mutant genes grizzled (gr), mocha (mh), mocha 2J (mh2J),
      jittery (ji) and hesitant (ji(hes)), which map to this area, excluded mutations
      in their Palm coding sequences.

PMID- 9615235
TI  - Localization of human cadherin genes to chromosome regions exhibiting cancer
      related loss of heterozygosity.
AB  - This report presents the chromosomal localization of cadherin genes. Cadherins
      are cellular adhesion molecules. Since disturbance of intracellular adhesion is
      important for invasion and metastasis of tumor cells, cadherins are considered
      prime candidates for tumor suppressor genes. A variety of solid tumors show loss
      of heterozygosity of the long arm of chromosome 16, which is indicative of the
      potential location of tumor suppressor genes. Refined and new localizations of
      six cadherin genes (CDH3, 5, 8, 11, 13, and 15) to the long arm of chromosome 16
      are shown. CDH15 was localized to 16q24.3, in a region that exhibits loss of
      heterozygosity in a number of sporadic breast cancer tumors. Previous
      localization of CDH13 (H-cadherin) to 16q24 suggested this gene as a tumor
      suppressor candidate in the 16q24.3 loss of heterozygosity region; however,
      refined mapping presented in this report localizes CDH13 proximal to this region.
      A human EST homologous to the chicken cadherin-7 was partially sequenced and
      found to represent a new human cadherin. This cadherin mapped to chromosome 18q22
      q23, a region that exhibits loss of heterozygosity in head and neck squamous cell
      carcinomas. CDH16 was localized to 8q22.1, a region exhibiting loss of
      heterozygosity in adult acute myeloid leukemia.

PMID- 9615236
TI  - Assignment of the gene encoding the limbic system-associated membrane protein
      (LAMP) to mouse chromosome 16B5 and human chromosome 3q13.2-q21.

PMID- 9615237
TI  - Map location and gene structure of the Homo sapiens mitotic arrest deficient 2
      (MAD2L1) gene at 4q27.

PMID- 9615239
TI  - Measuring community capacity: where do we go from here?
AB  - Goodman et al. have set us off on our journey to articulate and measure the
      dimensions of community capacity. While we have tried to identify some of the
      areas for future exploration, it is clear that this should be an ongoing process.
      Moreover, it is important that the process used to develop measures, assess
      capacity, and use the information to intervene be consistent with the intended
      outcome--building community capacity. In other words, at a minimum, the process
      should be cognizant of the history of the community, be participatory (i.e.,
      incorporate the multitude of voices involved, particularly those of the community
      members themselves) and use the skills and resources available in professional,
      academic, and community settings. Perhaps most important, this dialogue must
      begin from a place of respect for the multitude of perspectives that need to be
      brought to bear to enhance community capacity to create healthful changes.

PMID- 9615238
TI  - Identifying and defining the dimensions of community capacity to provide a basis
      for measurement.
AB  - Although community capacity is a central concern of community development
      experts, the concept requires clarification. Because of the potential importance
      of community capacity to health promotion, the Division of Chronic Disease
      Control and Community Intervention, Centers for Disease Control and Prevention
      (CDC), convened a symposium in December 1995 with the hope that a consensus might
      emerge regarding the dimensions that are integral to community capacity. This
      article describes the dimensions that the symposium participants suggested as
      central to the construct, including participation and leadership, skills,
      resources, social and interorganizational networks, sense of community,
      understanding of community history, community power, community values, and
      critical reflection. The dimensions are not exhaustive but may serve as a point
      of departure to extend and refine the construct and to operationalize ways to
      assess capacity in communities.

PMID- 9615240
TI  - Radon awareness and reduction campaigns for African Americans: a theoretically
      based evaluation.
AB  - Radon gas is a significant health threat linked to thousands of preventable
      deaths each year. One population that may be at increased risk from harm from
      radon exposure is African Americans. However, little is known about what African
      Americans think or know about radon. A theoretically based evaluation of radon
      awareness and reduction campaigns was conducted with African Americans. The
      knowledge and perceptions results indicate that African Americans often hold
      inaccurate beliefs regarding radon (e.g., confusing it with carbon monoxide gas),
      perceive it to be a serious threat, and perceive recommended responses to be
      inadequate in averting harm. The campaign materials evaluation shows that
      campaign materials often promote perceptions of threat but not perceptions of
      efficacy regarding recommended responses. Recommendations are given for public
      health practitioners.

PMID- 9615241
TI  - Sociopsychological correlates of motivation to quit smoking among low-SES African
      American women.
AB  - This article examines correlates of desire and plans to quit smoking among 248
      young, low-socioeconomic status African American women, using variables derived
      from the health belief model (HBM) and the theory of reasoned action. Consistent
      with these theoretical models, stronger concern about the effect of smoking on
      one's health and having close others who want the smoker to quit increased
      motivation to quit smoking. However, motivation was not associated with specific
      HBM components regarding lung cancer. Heavier smoking and stronger perceptions
      regarding the functional utility of smoking decreased motivation to quit, but not
      as much as expected in this study population. Consistent with a process of change
      approach to smoking cessation, the factors that moved smokers from not planning
      to planning to ever quit were different from factors associated with further
      motivation level among the smokers who did plan to ever quit.

PMID- 9615243
TI  - Factors that contribute to effective community health promotion coalitions: a
      study of 10 Project ASSIST coalitions in North Carolina. American Stop Smoking
      Intervention Study for Cancer Prevention.
AB  - The purpose of this study was to identify factors that contribute to the
      effectiveness of community health promotion coalitions. Member survey data from
      10 coalitions formed as part of North Carolina Project ASSIST were analyzed at
      the coalition level to identify factors related to member participation, member
      satisfaction, quality of the action plan, resource mobilization, and
      implementation. The results suggest that coalitions with good communication and
      skilled members had higher levels of member participation. Coalitions with
      skilled staff, skilled leadership, good communication, and more of a task focus
      had higher levels of member satisfaction. Coalitions with more staff time devoted
      to them and more complex structures had greater resource mobilization, and
      coalitions with more staff time, good communication, greater cohesion, and more
      complex structures had higher levels of implementation. Neither member
      participation nor member satisfaction correlated with the other measures of
      coalition effectiveness.

PMID- 9615242
TI  - The Authoritative Parenting Index: predicting health risk behaviors among
      children and adolescents.
AB  - Public health research demonstrates increasing interest in mobilizing parental
      influence to prevent health risk behaviors among children and adolescents. This
      research focuses on authoritative parenting, which previous studies suggest can
      prevent health risk behaviors among youth. To evaluate the reliability and
      validity of a new survey measure of authoritative parenting, data from studies of
      (1) substance use in a sample of 1,236 fourth- and sixth-grade students; (2)
      weapon carrying and interpersonal violence in a sample of 1,490 ninth- and tenth
      grade students, and (3) anger, alienation, and conflict resolution in a sample of
      224 seventh- and eighth-grade students were analyzed. The Authoritative Parenting
      Index had a factor structure consistent with a theoretical model of the
      construct; had acceptable reliability; showed grade, sex, and ethnic differences
      consistent with other studies; and identified parenting types that varied as
      hypothesized with multiple indicators of social competence and health risk
      behaviors among children and adolescents.

PMID- 9615244
TI  - Kasdah B'Rosh Tov: a description and evaluation of the Israeli bicycle helmet
      campaign.
AB  - In this article, the Israeli bicycle helmet campaign that began in 1993 and was
      accompanied both by increases in sales of helmets and by increases in their use
      by children is described and evaluated. Based on formative research, the authors
      designed a campaign by applying functional theories of attitudes. Evaluative
      research allowed testing the suitability of this application. Results supported
      functional predictions. Children's exposure to an initial pilot campaign was
      associated with changes in normative perceptions of helmet wearing and with
      increased willingness to wear a helmet. Their exposure to the subsequent
      comprehensive campaign was associated with changes in utilitarian beliefs but not
      with increased willingness to wear helmets. Parents' exposure to the
      comprehensive campaign was associated with changes in utilitarian beliefs, but
      their willingness to require their children to wear helmets was limited by their
      perceived ability to succeed in influencing their children's use of helmets.

PMID- 9615245
TI  - Weight loss management: a path lit darkly.
AB  - This article reviews recent research on the prevalence and virulence of obesity
      as a causal risk factor for mortality and morbidity. The prevailing assumption
      that obesity, by itself, is a chronic disease or a primary risk factor for health
      is challenged. A historical perspective is used to analyze the efficacy of
      various medical and educational approaches that have attempted to alter body size
      in the pursuit of enhanced physical health. The motivational discrepancies
      between society's media-induced desire for thinness and the health field's risk
      reduction approach to weight loss are outlined. Finally, ethical issues are
      raised in relation to current weight control measures, implications for future
      educational efforts are discussed, and potential guidelines for future weight
      management programs are presented.

PMID- 9615246
TI  - A health priorities model: application to mammography screening.
AB  - This study describes and empirically tests a health priorities model. This model
      predicts underuse of regular mammography screening among adult women within the
      larger health context in which such decisions are made. The model incorporates
      women's comparative illness threats, comparative importance of health behaviors,
      and demographic variables. A telephone survey was conducted with a sample of
      women (N = 887) older than 50, in 40 rural communities in the state of
      Washington. Logistic regression analyses showed that women who perceived
      themselves at low risk for getting breast cancer and/or who perceived another
      disease (i.e. heart attack) as an equal or greater threat than breast cancer were
      less likely to be regular screeners of mammography. In addition, women who
      perceived other health behaviors as more important than regular mammography
      screening were less likely to be regular screeners than those women who perceived
      regular mammography screening as more important. Current or anticipated health
      problems were not related to screening behavior. The results are discussed in
      light of the practical, theoretical, and empirical implications.

PMID- 9615247
TI  - Recent progress in the biology of multiple myeloma and future directions in the
      treatment.
AB  - A great amount of scientific information, accumulated over recent years on the
      biology of Multiple Myeloma (MM), has fuelled speculation about the origin of
      malignant plasma cells, about a purported critical role played by the bone marrow
      stroma, and further still, on cytokine interactions and in particular that of IL
      6 and its relationship with the immune system. Among the growth factors secreted
      by stroma cells, IL-6 is a potent stimulator of myeloma cells in vitro but does
      not induce a malignant phenotype in normal plasma cells. Many efforts have been
      produced to identify the stem cell in MM and probably memory B lymphocytes are
      the best candidates. The demonstration of a Graft vs Myeloma effect in the
      allogeneic setting strongly supports the immunotherapy in MM. Recent data also
      suggest that a virus (Kaposi-associated herpes virus, HHV-8) may be significantly
      associated with the development of MM. In parallel, progress has been achieved in
      the treatment of this incurable disease with well defined prognostic factors,
      more efficient supportive care and its corollary, improved quality of life and
      dose-intensified chemo-radiotherapy followed by autologous hematopoietic stem
      cell support. Improving the quality of grafts with the selection of CD34 positive
      cells is another approach aimed at reducing plasma cell contamination without
      impairing haematological recovery. An EBMT randomized study assessing the role of
      CD34 selection has been initiated by our group Increasingly efficient first-line
      therapy, better quality autografts and improved post-remission treatment with,
      for example, anti-idiopathic vaccination are the most promising future
      directions.

PMID- 9615248
TI  - Granulocyte-macrophage colony-stimulating factor in post-remission therapy of
      acute myeloid leukemia.
AB  - The impact on occult leukemia of GM-CSF as a sensitizing agent has not been
      studied. We treated 41 adult patients with de novo acute myeloid leukemia, 25 of
      whom achieved complete remission and were given 1 to 3 post-remission courses,
      each course including GM-CSF begun 4 days prior to chemotherapy and given until
      day 3. After a median follow-up of 32 months, the probability of remaining in
      continuous complete remission was 17% at 46 months. GM-CSF in this setting was
      not associated with an improved outcome, arguing against a priming effect.

PMID- 9615249
TI  - Simultaneous administration of antithrombin III and protein C concentrates for
      the treatment of a devastating coagulopathy in a child.
AB  - Severe disseminated intravascular coagulation (DIC) is a rare event in childhood.
      We report here a young body with a devastating DIC unresponsive to heparin, fresh
      frozen plasma and platelet support. This prompted the use of antithrombin III and
      protein C concentrates and the effects of this combination were temporarily
      spectacular. We suggest that the simultaneous administration of two inhibitors of
      blood coagulation could be of interest and should be evaluated in appropriate
      trials for the treatment of a devastating coagulopathy.

PMID- 9615250
TI  - Spontaneous recovery from severe parvovirus B19 pure red cell aplasia, in a heart
      transplant recipient, as demonstrated by marrow culture.
AB  - A 61-year-old heart transplant recipient with parvovirus B19 infection, presented
      as a severe pure red cell aplasia (PRCA) with hemoglobin level of 5 g/dl. Both
      blood and bone marrow cells were positive for parvovirus B19 DNA, whereas
      specific immunoglobulins IgG and IgM were not informative. Bone marrow smears
      revealed erythroid hypoplasia without giant pronormoblasts. Autologous and
      allogenic bone-marrow cultures revealed a high inhibition by patient's serum on
      BFU-E growth whereas the number of CFU-GM were normal. Spontaneous remission of
      the anemia was observed despite the persistence of severe immunodeficiency as
      demonstrated by development of a monoclonal EBV lymphoproliferative disorder two
      months later. The "recovery" serum reversed the initial serum BFU-E inhibiting
      property. This case pinpointed the usefulness of blood or marrow cultures in
      parvovirus B19 infection of immunocompromised patients without normal Ig
      responses, as in other PRCA. Further, it argues that the usual immunoglobulin
      therapy may not be necessary in order to obtain a viral clearance.

PMID- 9615251
TI  - The self-concept of the elderly: a cross-cultural comparison.
AB  - This study examines the self-concept of the elderly in a cross-cultural
      perspective. An open-ended sentence completion methodology was employed. A sample
      of elderly Spanish and elderly Dutch were compared to gain an idea of the cross
      cultural generality of the content of the self-concept. Analysis focuses on
      responses to sentences which probed the respondents' motivations and future plans
      and goals. Differences could be interpreted as reflecting an individualistic
      (Dutch) vs. collectivistic (Spanish) distinction between the two cultures.
      Furthermore, the findings had implications for how to interpret dimensions of
      meaningful aging. For example, a dimension such as "purpose in life" was more
      generalizable across the two samples than a dimension such as "autonomy."

PMID- 9615252
TI  - Inner-ages of middle-aged prime-lifers.
AB  - A comprehensive survey examined three age-role self-concepts: cognitive, ideal,
      and social ages. Participants were forty to sixty-nine years old and viewed
      themselves as middle-aged. The investigation reviewed inner-age research and
      evaluated inner-age infra-structure (with t-tests and correlations), as well as
      connections between inner-age and participants' characteristics (with covariates,
      partial correlations, and regressions) in the context of eight psychographic
      trait-sets (sex-identity, quality-of-life, health, self-consciousness, societal
      traits, venturesomeness, supermarket shopping involvement, and exercise
      activities). The three inner ages, while closely interrelated diverged in their
      distribution patterns, in mean ages, as well as (after removal of birth age's
      linear effects) in their covariates and correlates.

PMID- 9615253
TI  - Older people--the reserve army of volunteers?: an analysis of volunteerism among
      older Australians.
AB  - In Australia, as in other Western countries, policy-makers are turning their
      attention to older people, particularly the early retired, as a rich potential
      source of volunteers. This study examines volunteer behavior in a sample of older
      Australians in either their immediate pre or post retirement phase. It involves a
      secondary analysis of data collected for a study on retirement, and seeks to
      examine the main social and demographic differences between those who volunteer
      and those who do not. The key concepts associated with volunteering are the
      availability of 1) time and 2) social and personal resources. Logistic regression
      analyses revealed that volunteers are significantly more likely to come from the
      higher occupational classes, are less likely to be self-employed, and are more
      likely to view their health positively. Implications of these results for social
      policy are discussed.

PMID- 9615254
TI  - Exploring intra-ethnic diversity among four groups of Hispanic elderly: patterns
      and levels of service utilization.
AB  - This study investigates service use by a sample of 2,135 Hispanic elderly in
      order to address the issue of the homogeneity or heterogeneity within the older
      Hispanic population as revealed by the use of formal services. Factor analysis
      revealed a high degree of homogeneity in the patterns of formal service use among
      the four Hispanic groups in this study that follows three latent, but distinct,
      patterns of behavior: the use of federal entitlement programs, in-home services,
      and senior center services. Although the patterns of service use reflect
      substantial homogeneity among the Hispanics in this sample, there is a high
      degree of heterogeneity in the level of service use. Overall, service use was
      systematically lower among "Other" Hispanic elders and systematically higher
      among Puerto Rican elders, with somewhat more erratic use among Cuban American
      and Mexican American elders. Controlling for between-group differences in socio
      demographic characteristics did little to reduce relatively systematic between
      group differences in levels of service use.

PMID- 9615255
TI  - For a cultural change in drug prescriptions in gastroenterology.

PMID- 9615256
TI  - Gastric MALT lymphomas, new insight and still unanswered questions.

PMID- 9615257
TI  - Quality of life assessment in gastro-oesophageal reflux disease. Why and when?

PMID- 9615258
TI  - Non steroidal anti-inflammatory drugs, cyclooxygenase selectivity and
      gastrointestinal toxicity.

PMID- 9615259
TI  - Quality of life during acute and intermittent treatment of gastro-oesophageal
      reflux disease with omeprazole compared with ranitidine. Results from a
      multicentre clinical trial. The European Study Group.
AB  - AIMS: To investigate quality of life in patients with gastro-oesophageal reflux
      disease. PATIENTS: A series of 704 patients were randomised to treatment with
      ranitidine 150 mg bd, omeprazole 10 mg om or omeprazole 20 mg om for 2 weeks.
      Asymptomatic/mildly symptomatic patients were followed for 12 months. METHODS:
      The Psychological General Well-Being index and the Gastrointestinal Symptom
      Rating Scale were completed before and during short-term and intermittent
      treatment. RESULTS: The quality of life response rate was > 80%. The majority of
      the patients receiving omeprazole 20 mg om (55%) had symptom relief after 2 weeks
      despite the fact that more patients on ranitidine required 4 weeks' treatment and
      an increased dose. There was no difference in the reflux dimension of
      Gastrointestinal Symptom Rating Scale between treatments in the initial treatment
      phase, but the total Gastrointestinal Symptom Rating Scale score improved
      significantly more on omeprazole 10 mg om than on ranitidine 150 mg bd (p =
      0.006). Both doses of omeprazole improved the total Psychological General Well
      Being score more than ranitidine (omeprazole 10 mg om versus ranitidine 150 mg
      bd, p = 0.005, omeprazole 20 mg om versus ranitidine 150 mg bd, p = 0.031).
      During follow-up, relapsing patients returned to pre-treatment symptom and well
      being scores, but these dimensions were restored after treatment. CONCLUSION: The
      quality of life is impaired in patients presenting with reflux symptoms.
      Irrespective of whether the patients presented with endoscopy positive or
      endoscopy negative reflux disease, treatment on demand improved the quality of
      life.

PMID- 9615260
TI  - Increased risk for Helicobacter pylori recurrence by continuous acid suppression:
      a randomized controlled study.
AB  - BACKGROUND AND AIMS: Acid hyposecretion may enhance Helicobacter pylori
      colonization. We tested the hypothesis that maintenance therapy with ranitidine
      after cure of Helicobacter pylori infection increases the risk of recurrence of
      infection. PATIENTS AND METHODS: Sixty-six patients with duodenal ulcer and cured
      Helicobacter pylori infection were randomly assigned to 12 months maintenance
      treatment with ranitidine 150 mg daily (group A) or no treatment (group B).
      Follow-up consisted of clinical and endoscopic controls with biopsies for
      histology and rapid urease test every 4 months. RESULTS: Six patients, 3 in each
      group, were lost to follow up. Helicobacter pylori recurrence occurred in 9
      patients in group A and in 2 patients in group B (30% versus 7%; p < 0.05).
      Duodenal ulcer recurred in one patient in group A and in 2 in group B, all three
      patients were reinfected with Helicobacter pylori. A corpus-predominant gastritis
      was observed in all reinfected patients in group A but in none in group B.
      CONCLUSIONS: Long-term inhibition of gastric acid secretion after eradication of
      Helicobacter pylori increases the risk of recurrence of infection. Our data imply
      that gastric acid not only influences the pattern of Helicobacter pylori
      localization in gastric mucosa, but also plays a key role in preventing
      recurrence of infection with Helicobacter pylori.

PMID- 9615261
TI  - Reacquisition of Helicobacter pylori following eradication: does long-term acid
      suppression really matter?

PMID- 9615262
TI  - Mucosal and systemic antibody levels against Helicobacter pylori do not parallel
      gastric inflammatory changes.
AB  - BACKGROUND AND AIMS: Mucosal and systemic antibodies against Helicobacter pylori
      have been detected but their role in the natural history of Helicobacter pylori
      related diseases is unclear. In this study, the levels of Helicobacter pylori IgG
      and IgA were related to the grade of gastritis. PATIENTS AND METHODS: A series of
      152 dyspeptic patients underwent gastroscopy with biopsies. Helicobacter pylori
      was detected in 131 (86%) patients. Samples of serum and unstimulated saliva were
      collected. Helicobacter pylori IgG and IgA were measured in homogenised gastric
      biopsies, saliva and serum by an in-house enzyme linked immunosorbent assay.
      RESULTS: Levels of gastric mucosa, salivary and serum Helicobacter pylori IgG
      were higher (p < or = 0.01) in Helicobacter pylori positive than negative
      patients. Likewise, levels of gastric mucosa and serum Helicobacter pylori IgA
      were higher (p < 0.01) in Helicobacter pylori positive patients. Gastric mucosa,
      saliva and serum Helicobacter pylori antibody levels did not differ between
      superficial and atrophic, active and inactive Helicobacter pylori positive
      gastritis. CONCLUSIONS: These data indicate that gastric inflammatory changes may
      not necessarily be related to the antibody response against Helicobacter pylori.

PMID- 9615263
TI  - Gleanings on Helicobacter pylori infection, antigenic profile of strains, host's
      immune response.

PMID- 9615264
TI  - Prevention of gastroduodenal damage with omeprazole in patients receiving
      continuous NSAIDs treatment. A double blind placebo controlled study.
AB  - AIM: The aim of this study was to compare omeprazole (20 mg once daily) with
      placebo in the long-term prevention of gastroduodenal lesions induced by
      indomethacin, diclofenac and ketoprofen. PATIENTS AND METHODS: 114 patients with
      arthritic disorders and requiring indomethacin, diclofenac or ketoprofen were
      randomized in a double blind manner to receive omeprazole-20 mg once daily- or
      identical placebo for three weeks. The gastroduodenal mucosa damage was scored
      according to a 0-4 point endoscopic scale. RESULTS: Of the 114 patients, 103 (50
      in the omeprazole group, 53 in the placebo group) were submitted to endoscopy,
      while 11 patients dropped out for non-medical reasons. At the final endoscopy,
      26/57 (46%) of omeprazole group, and 20/57 (35%) of the placebo group had normal
      gastroduodenal mucosa (score = 0) (p ns; 95% IC -0.073 + 0.284). A gastric ulcer
      was observed in 7/57 (12%) patients, all in the placebo group (p < 0.01 vs
      omeprazole); 2 patients (1 in the omeprazole group and 1 in the placebo group)
      developed a duodenal ulcer. Dyspeptic symptoms developed in 10% of the patients
      treated with omeprazole and 29% of those receiving placebo (p ns). CONCLUSIONS:
      Omeprazole, 20 mg once daily, provides effective prophylactic therapy in patients
      at risk of developing NSAID-associated gastric and duodenal ulcer.

PMID- 9615265
TI  - Non steroidal anti-inflammatory drugs. Minimising the harm, maximising the
      benefit.

PMID- 9615266
TI  - A capture-recapture estimate of inflammatory bowel disease prevalence: the
      Florence population-based study.
AB  - BACKGROUND: A recent population-based epidemiological study identified the
      patients with a diagnosis of ulcerative colitis or Crohn's disease resident in
      the metropolitan Florence area in the period 1978-1992 and defined their vital
      status on 31 December, 1992. AIMS: To estimate the completeness of Inflammatory
      Bowel Disease prevalent case ascertainment in the study area. SUBJECTS AND
      METHODS: In a Registry, specifically developed during the study, 767 patients
      fulfilled the criteria for the definition of prevalent cases as of 31 December,
      1992. At the same time, we had access to an independent source of potential
      patients: the Regional Health Department kept a list of all Inflammatory Bowel
      Disease patients allowed free access to specific health care provided only to
      selected diagnostic categories. We then compared the two different sources and
      used a capture recapture analysis to estimate the number of cases missed by both
      sources. RESULTS: A total of 331 patients were reported by both sources, 436 were
      found only in the Registry while a large group of potential cases not present in
      our Registry was found only in the List. After careful confirmation of the
      diagnosis for each individual patient and contact with his/her physician, we
      identified an additional 102 cases that were included in the final population
      series of 869 prevalent cases. This capture-recapture analysis led to a revised
      estimate of 1,003 prevalent cases, suggesting that 134 patients had been missed
      by both sources, resulting in an Inflammatory Bowel Disease prevalence rate of
      186 per 100,000. CONCLUSIONS: According to this method our previous study
      underestimated the true prevalence of 13.4% (95% confidence interval: 9.8-16.6%).
      On account of some degree of negative dependence between the two sources the loss
      was probably in the lower range of this interval. Completeness of case
      ascertainment should be evaluated and discussed in all studies designed to
      provide population-based estimates for health care planning.

PMID- 9615267
TI  - How much inflammatory bowel disease is there?

PMID- 9615268
TI  - HLA antigens and pANCA define ulcerative colitis as a genetically heterogeneous
      disorder.
AB  - BACKGROUND: Several genetic and subclinical markers have been associated with
      ulcerative colitis. AIM: To determine whether a significant association with HLA
      class I and II antigens was present in Italian ulcerative colitis patients
      considered as a whole population or stratified according to their anti-neutrophil
      cytoplasmatic antibodies. METHODS: HLA class I and II antigens were studied by
      serological typing techniques and related to the presence of anti-neutrophil
      cytoplasmatic antibodies detected by means of indirect immunofluorescence.
      RESULTS: Patients with ulcerative colitis (n = 45) had a significantly increased
      frequency of DQ6 (p = 0.04) and DQ7 (p = 0.003) and a decreased frequency of DQ5
      (p = 0.03) and DQ8 (p = 0.02) when compared with ethnically matched healthy
      controls (n = 252 for HLA class I and 173 for HLA class II). No significant
      difference in HLA I- and DR-antigens was observed. Anti-neutrophil cytoplasmatic
      antibodies were found in 27/45 (60%) ulcerative colitis patients and in 0/252
      controls (p < 0.001). After stratifying ulcerative colitis patients according to
      their anti-neutrophil cytoplasmatic antibodies status, anti-neutrophil
      cytoplasmatic antibodies +ve patients had an increased frequency of A19 (p =
      0.007), DR2 (p = 0.03), and DR15 (p = 0.006), and a decreased frequency of A1 (p
      = 0.004) compared with anti-neutrophil cytoplasmatic antibodies -ve ones.
      CONCLUSIONS: We suggest that specific HLA-class II loci play an important role in
      the susceptibility to ulcerative colitis in Italy. A subset of ulcerative colitis
      patients is characterised by the presence of a specific subclinical marker (anti
      neutrophil cytoplasmatic antibodies) which seems to be genetically determined as
      shown by the increased frequencies of HLA-A19 and DR2 observed in anti-neutrophil
      cytoplasmatic antibodies +ve ulcerative colitis.

PMID- 9615269
TI  - Substance P and vasoactive intestinal polypeptide but not calcitonin gene-related
      peptide concentrations are reduced in patients with moderate and severe
      ulcerative colitis.
AB  - BACKGROUND AND AIMS: Ulcerative colitis is a chronic inflammatory condition
      characterized by an altered intestinal immunoinflammatory response. Since
      increasing evidence indicates that neuropeptides play a key role in the
      regulation of gastrointestinal immune function, the aims of this study were: a)
      to determine tissue and plasma levels of Vasoactive Intestinal Polypeptide,
      Substance P, and Calcitonin Gene-Related Peptide in patients with ulcerative
      colitis, and b) to ascertain whether a relationship exists between tissue
      concentrations of neuropeptides and the histological grading of mucosal
      inflammation. METHODS: A total of 29 patients with active and 39 with inactive
      ulcerative colitis, and 16 control subjects took part in the study. Biopsy
      specimens of colonic mucosa and blood samples were obtained from each subject,
      and neuropeptide concentrations were measured by sensitive and specific
      radioimmunoassays. RESULTS: Both Vasoactive Intestinal Polypeptide and Substance
      P concentrations were found to be significantly reduced in endoscopic biopsy
      specimens of patients with ulcerative colitis compared to controls (p < 0.01 and
      p = 0.05, respectively), and the reduction appeared to be related to the degree
      of mucosal inflammation; in contrast, Calcitonin Gene-Related Peptide tissue
      levels were unchanged. In addition, there was no significant difference in the
      neuropeptide plasma levels between ulcerative colitis patients and control
      subjects. CONCLUSIONS: Taken together, our results suggest that the reduction of
      Vasoactive Intestinal Polypeptide and Substance P is probably a secondary
      phenomenon, correlated with the degree of mucosal inflammation; whatever the
      mechanism, the decreased availability of these neuropeptides in the local
      microenvironment may play an important role in the pathogenesis of ulcerative
      colitis, by affecting many components of the normal immune response. Moreover,
      based on our data, the measurement of neuropeptide plasma concentrations does not
      appear to be a useful tool to monitor disease activity.

PMID- 9615270
TI  - Organ-specific autoimmunity and genetic predisposition in interferon-treated HCV
      related chronic hepatitis patients.
AB  - AIMS: Interferon alpha has been reported to enhance autoantibody production and
      to increase the risk of autoimmunity particularly against thyroid tissue. We
      designed a study with the following aims: 1) to assess the incidence of organ-
      and non-organ-specific autoantibodies during Interferon treatment; 2) to evaluate
      whether these autoantibodies have any clinical relevance; 3) to establish whether
      the development of autoimmune disorders can be related to a genetic
      predisposition. METHODS: A panel of 5 non-organ-specific and 6 organ-specific
      autoantibodies was evaluated in serum samples collected before treatment and then
      at 3 and 12 months in 47 patients enrolled in a treatment protocol with a 2b
      recombinant Interferon (3 MU, 3 times a week for 12 months). In the second part
      of the study we explored genetic predisposition for autoimmune disorders in 31
      patients by DNA-HLA class II typing using Restriction Fragment Length
      Polymorphism (RFPL). RESULTS: Non-organ-specific autoantibodies were absent in
      all patients before and after Interferon. During follow-up 6 patients showed an
      increment in thyroid microsomal antibody titres; 3 of these also developed
      thyroglobulin autoantibodies; 3 of the 6 patients developed persistent
      hypothyroidism; a fourth had a transient subclinical hypothyroidism and a fifth
      had a transient subclinical hyperthyroidism. Two patients with initial positivity
      for ICA and PCA maintained their reactivity during treatment without impairment
      of the respective target organs. Eight out of 39 initially negative patients
      developed one or more organ-specific autoantibodies during follow-up. One of
      these developed a persistent hypothyroidism, and another developed insulin
      dependent diabetes. HLA-typing did not reveal any particular allele frequency in
      patients with thyroid antibody positivity as compared with those without
      autoantibodies and controls. Moreover, four of the 6 patients positive for islet
      cell antibodies were carrying the non-Asp 57 allele which is considered a marker
      of a genetic predisposition for insulin-dependent diabetes. CONCLUSIONS: These
      findings suggest that, besides the thyroid gland, pancreatic beta-cells could be
      a target of autoimmunity during Interferon-treatment for chronic HCV hepatitis. A
      genetic predisposition may be important, though insufficient alone, in the
      development of Interferon-induced autoimmune phenomena.

PMID- 9615271
TI  - Recurrence of hepatitis B in liver transplants treated with antiviral therapy.
AB  - BACKGROUND AND AIMS: In patients with terminal Hepatitis B Virus-related liver
      diseases, liver transplantation carries a consistent risk of Hepatitis B Virus
      recrudescence in the graft. In the attempt to reduce the reinfection rate with
      antiviral therapy, we studied a total of 16 viraemic patients. PATIENTS AND
      METHODS: Twelve patients received Ganciclovir, starting 4-67 days (mean 25 days)
      before transplantation and prolonged for 10 days after transplantation; four
      patients were treated with Lactosaminated Arabinoside-Monophosphate 6 hours
      before surgery and prolonged for 28 days after surgery. All received hepatitis B
      immunoglobulins. RESULTS: At transplantation, HBV-DNA had decreased to about
      10(4) virus/ml (as assessed by the polymerase chain reaction assay) in 10 of the
      12 patients treated with Ganciclovir. Of these patients, 4 died perioperatively
      from causes unrelated to Hepatitis B Virus reinfection. Of the eight survivors,
      only the patient who maintained a titre of 10(6) virus/ml at the time of
      transplantation developed viral recurrence 4 months after surgery. Before
      transplantation, 2 of the patients treated with Lactosaminated Arabinoside
      Monophosphate had a viraemic load of 10(6) and 2 of 10(4) virus/ml. In all cases,
      viraemia became undetectable at the end of therapy. None died and Hepatitis B
      Virus recurred 2 months after transplantation in one. The overall rate of
      Hepatitis B Virus recurrence was 16.6%. The recurrence rate decreased to 9% in
      patients in whom the viraemic load decreased to around 10(4) virus/ml following
      treatment, compared to an overall recurrence rate of 50% in our historical series
      of patients transplanted for Hepatitis B Virus-related cirrhosis. CONCLUSION:
      Antiviral therapy was effective in decreasing the risk of Hepatitis B Virus
      reinfection of the liver graft by decreasing the viral load before surgery.

PMID- 9615272
TI  - Gastric and intestinal ethanol toxicity in the rat. Effect on glutathione level
      and role of alcohol and acetaldehyde metabolisms.
AB  - BACKGROUND/AIMS: This study investigated the dose- and time-dependent effect of
      ethanol on gastric and intestinal glutathione and protein oxidative state in the
      rat. METHODS: Rats received 1 or 4 g/kg of 25% ethanol solution orally or
      isocaloric glucose. Some rats received diethylmaleate, cimetidine or cyanamide
      before ethanol (1 g/kg). Glutathione, carbonyl proteins and histological damage
      were evaluated in the gastric and intestinal mucosa 6 hours after treatment.
      RESULTS: An increase in glutathione was observed 2 to 6 hours after 1 g/kg of
      ethanol both in the gastric and intestinal mucosa, whereas 4 g/kg decreased
      glutathione. The rise in glutathione after ethanol was associated with increased
      levels of its oxidized form; however, the total/oxidized ratio was significantly
      decreased only in the intestinal tract. Diethylmaleate depleted mucosal
      glutathione, while the subsequent ingestion of ethanol increased it. Unlike
      stomach, intestine showed a significant increase in carbonyl proteins and marked
      histological lesions after ethanol ingestion. Cimetidine and cyanamide inhibited
      by 50% the activity of alcohol dehydrogenase and by 80% aldehyde dehydrogenase,
      respectively, in the gastric and intestinal mucosa. Cyanamide significantly
      enhanced ethanol-induced protein oxidation and mucosal injury in the stomach. No
      such effect was observed in the intestine. CONCLUSIONS: The increase of
      glutathione after ingestion of low amounts of ethanol appears to be an adaptive
      mechanism against ethanol toxicity. Depletion of glutathione increased protein
      oxidation and the extent of histological damage in ethanol-treated rats. At
      gastric level, the effects of ethanol are exaggerated by the inhibition of
      acetaldehyde metabolism; while intestinal damages appear to be ascribed to
      ethanol itself.

PMID- 9615273
TI  - Endoscopy in the treatment of benign biliary strictures.
AB  - BACKGROUND/AIMS: Operative endoscopy is now the method of choice for treating
      numerous biliary tree diseases. In the treatment of benign strictures of the
      biliary tree, endoscopy serves as an alternative to surgical interventions. We
      evaluated the efficacy of endoscopic biliary stents in the treatment of benign
      biliary strictures. PATIENTS: Fifty-three consecutive patients with benign
      strictures of the biliary tree underwent endoscopic placement of one or more 10
      12 Fr endoprostheses. Thirty-nine patients (73.6%) had iatrogenic strictures and
      14 had inflammatory strictures (in 8 patients due to gallstones and in 6, chronic
      pancreatitis). Of the 53 patients, 20 (37.7%) had strictures classified as
      Bismuth type I, 23 (43.3%) Bismuth type II, 7 (13.2%) Bismuth type III and 3
      (5.7%) Bismuth type IV. RESULTS: None of the patients died during the study
      period; three patients (5.6%) had immediate endoscopy-related complications
      treated conservatively. Late complications developed in 47.1% of the patients:
      11.3% had cholangitis amenable to medical therapy, 5.6% had dislodged
      endoprostheses and 30.2% had obstructed endoprostheses. The reason why blocked
      stents accounted for most of the long-term complications in this series was that
      endoprostheses were not changed electively: they were changed only when clinical
      and laboratory signs indicated obstruction. Follow-up (6-84 months) in 42 of the
      56 patients. 20 after stent removal, showed that 71.4% had an excellent outcome,
      14.3% good results and 14.3% needed surgery. CONCLUSION: In benign biliary
      stricture endoscopic stenting is the first approach, providing definitive
      treatment or preparing patients for surgery.

PMID- 9615274
TI  - Main issues in push enteroscopy.
AB  - Endoscopic evaluation of the small bowel has rapidly evolved over the last ten
      years, marking an important milestone in the diagnosis and treatment of small
      bowel diseases. Gradual progress in endoscopic techniques and development of new
      instruments with full therapeutic options have aided and spread the use of
      enteroscopy. However, some basic issues concerning its appropriate use in
      clinical practice remain to be solved. This article stresses the importance of
      lesions missed at oesophagogastroduodenoscopy in patients with obscure
      gastrointestinal bleeding who undergo push enteroscopy, focuses on the limits of
      outcome studies related to therapeutic enteroscopy, and critically reviews the
      clinically relevant indications to push enteroscopy.

PMID- 9615275
TI  - For a cultural change in drug prescriptions in gastroenterology.

PMID- 9615276
TI  - Drug prescriptions in liver and biliary disease: something more to be done.

PMID- 9615277
TI  - Guidelines for the diagnostic and therapeutic management of patients with gastro
      oesophageal reflux disease. A position statement of The Italian Association of
      Hospital Gastroenterologists (AIGO), Italian Society of Gastrointestinal
      Endoscopy (SIED), and Italian Society of Gastroenterology (SIGE).

PMID- 9615278
TI  - Vascular and immunological disorders associated with Helicobacter pylori
      infection.
AB  - Helicobacter pylori, the main aetiological factor for gastritis and peptic ulcer
      has been associated with some extradigestive diseases. In particular, vascular
      disorders, such as ischaemic heart disease, primary Raynaud phenomenon and
      headache appear to be related to the presence of the bacterium. Moreover, some
      autoimmune diseases, such as Henoch-Schonlein purpura, Sjogren syndrome and
      others have been shown to have a link with Helicobacter pylori infection
      Probably, in subjects with a particular predisposition, the release of substances
      with a vasoactive and proinflammatory activity, which is determined by
      Helicobacter pylori infection, may influence some extradigestive districts.

PMID- 9615279
TI  - Helicobacter pylori infection and ischaemic heart disease: is there a link?
AB  - Several studies have recently reported an association between ischaemic heart
      disease and Helicobacter pylori infection. We critically review the
      epidemiological and clinical evidence on this association and examine the
      possible pathogenetic mechanisms by which Helicobacter pylori may increase the
      risk of developing ischaemic heart disease. The present evidence supporting the
      association between these two conditions is weak and based mainly on cross
      sectional surveys in which it is difficult or impossible to separate cause and
      effect; moreover, the sequence of gastric infection and heart disease is
      uncertain. Further prospective or interventional studies are needed to clarify
      this issue.

PMID- 9615280
TI  - Helicobacter pylori and the liver: any relationship?
AB  - Helicobacter pylori infection is being correlated to a number of human diseases,
      among which also those of the liver. From a clinical point of view, 4 "areas of
      interest" for the suggested correlation can be identified: 1. Helicobacter pylori
      and portal hypertension-related congestive gastropathy in cirrhotics. There are,
      in the literature, at least 7 studies confirming that the microorganism has no
      role in causing or worsening the disease. 2. Helicobacter pylori and duodenal
      ulcer in cirrhotic patients. Apparently, in the cirrhotic patient, the
      microorganism has no role in causing duodenal ulcer. 3. Helicobacter pylori,
      ammonia production and hepatic encephalopathy. In this case, there are at least
      three studies showing that Helicobacter pylori infection increases the risk of
      developing encephalopathy in the cirrhotic patient, this being a somewhat
      expected finding. 4. Helicobacter pylori infection in chronic liver disease and
      its diagnosis. Evidence in the literature suggests: a) that hypertensive
      gastropathy might not represent a favourable environment for Helicobacter pylori
      thus making the diagnostic sensitivity of the biopsy lower than expected, and b)
      that even serological diagnosis might provide data of difficult interpretation,
      as shown in non alcoholic cirrhosis and, by our own group, in primary biliary
      cirrhosis. More intriguing are the data generated with respect to the potential
      capacity of Helicobacter pylori and Helicobacter pylori-like bacteria such as, in
      particular, Helicobacter hepaticus to damage the liver by producing toxins with a
      granulating effect on liver cell lines which, in vivo, through the portal tract,
      might reach the liver, thus causing hepatocellular damage. The point has been
      addressed by a number of investigators and autoimmune mechanisms have also been
      suggested. In summary, from the clinical point of view, some evidence suggests
      that Helicobacter pylori infection might be relevant in the pathogenesis of
      hepatic encephalopathy in cirrhosis. The data being generated with respect to a
      direct hepatotoxicity are, at present, stimulating but only speculative.

PMID- 9615281
TI  - Helicobacter pylori and diminished growth in children: is it simply a marker of
      deprivation?
AB  - Helicobacter pylori is an accepted gastroduodenal pathogen and has recently been
      investigated for possible implications in non gastroenterological diseases such
      as growth impairment coronary heart disease and diabetes. Infection by cytotoxic,
      i.e., CagA or VacA positive strains seems more likely to lead to more serious
      gastroduodenal diseases compared to infection by non cytotoxic strains, but the
      possible role of CagA or VacA positive strains in non gastroenterological
      diseases has not been investigated. Aim of the present study was to evaluate the
      prevalence of Helicobacter pylori infection as well as CagA and VacA positivity
      in three paediatric populations auxologically normal, hyposomic and diabetic
      children. Sera from a total of 522 children (auxologically normal: 246,
      hyposomic: 164, diabetic: 112) were analyzed by a novel Recombinant ImmunoBlot
      Assay-Strip Immunoblot Assay--RIBA SIA--which contain individual band for whole
      Helicobacter pylori lysate and recombinant CagA and VacA. The overall
      seroprevalence of reactivities against Helicobacter pylori lysate, CagA and VacA
      were: 7.3%, 9.3%, 6.9% vs 11.6%, 7.9%, 8.5% vs 14.3%, 13.4%, 8% (p = NS) in
      auxologically normal, hyposomic and diabetic children, respectively. Summarizing,
      we found a similar prevalence of reactivity against both whole Helicobacter
      pylori lysate as well as recombinant CagA and VacA between auxologically normal,
      hyposomic and diabetic children. Our data do not support a possible role of
      Helicobacter pylori in diminished growth in children.

PMID- 9615282
TI  - Does Helicobacter pylori play a role in inflammatory bowel disease?
AB  - The cause of inflammatory bowel disease is still unknown although several
      bacterial and viral agents have been implicated in their aetiologies.
      Helicobacter pylori infection, the main cause of gastroduodenal diseases, could,
      theoretically, be involved in the pathogenesis of inflammatory bowel disease. In
      fact, it induces permeability alterations and immunological derangements in the
      stomach similar to those detected in the colon of inflammatory bowel disease
      patients. However, epidemiological data do not support this hypothesis and recent
      evidence even points to a low prevalence of Helicobacter pylori in inflammatory
      bowel disease. These data are discussed in the light of possible confounding
      factors.

PMID- 9615283
TI  - Sleep and circadian rhythms in four orbiting astronauts.
AB  - This experiment measured the sleep and circadian rhythms of four male astronauts
      aboard a space shuttle (STS-78) orbiting the Earth for 17 days. The space mission
      was specially scheduled to minimize disruptions in circadian rhythms and sleep so
      that the effects of space flight and microgravity per se could be studied. Data
      were collected in 72-h measurement blocks: one block 7 days before launch, one
      early within the mission (3 days after launch), one late in the mission (12 days
      after launch), and one 18 days after landing. Within each measurement block, all
      sleep was recorded both polysomnographically and by sleep diary. Core body
      temperature was sampled every 6 mins. Actillumes were worn continuously. All
      urine samples were collected separately. Performance was assessed by a
      computerized test battery (3/day) and by end-of-shift questionnaires (1/day);
      mood and alertness were measured by visual analogue scales (5/day). Circadian
      rhythms in orbit appeared to be very similar in phase and amplitude to those on
      the ground, and were appropriately aligned for the required work/rest schedule.
      There was no change from early flight to late flight. This was also reflected in
      mood, alertness, and performance scores, which were satisfactory at both in
      flight time points. However, in-flight sleep showed a decreased amount of sleep
      obtained (mean = 6.1 h), and all four astronauts showed a decrease in delta
      sleep. No further degradation in sleep was seen when early flight was compared to
      late flight, and no other sleep parameters showed reliable trends.

PMID- 9615284
TI  - Disturbances in hormonal profiles of night workers during their usual sleep and
      work times.
AB  - In a previous study, the authors reported that the 24-h rhythms of pituitary and
      adrenal hormones--that is, thyrotropin (TSH), prolactin (PRL), growth hormone,
      and cortisol--adapted only partially in a group of permanent night workers.
      However, the real impact of circadian rhythm alterations on the health and well
      being of subjects is still unclear. In this study, the authors focus on an
      ergonomic field and address questions of adaptation of these hormones during the
      usual day sleep time (0700-1500 h) and during the usual night work time (2200
      0600 h) in permanent night workers. Eleven night workers, working a night
      schedule for at least 2 years, submitted to a high-frequency blood sampling
      procedure (10 min) and to electroencephalographic recordings during sleep. The
      endocrine profiles of night workers were compared to those of day-active subjects
      studied during their usual sleep-wake schedule. During usual day sleep, despite
      an adapted sleep structure, cortisol levels among night workers were abnormally
      enhanced, whereas the TSH decreased in comparison to the plateau observed among
      day-active subjects. During usual work time, some hormonal disturbances
      persisted, in particular concerning cortisol and PRL (two hormones known to
      reflect the level of activation). Among night workers, the work time was
      associated with the quiescent period of cortisol secretion normally occurring
      during the first hours of sleep, and with a transient PRL increase. These results
      revealed altered hormonal profiles during the sleep time of night workers that do
      not result in an altered sleep pattern. The nocturnal work time, which requires a
      high level physical and mental performance, is associated with some endocrine
      alterations reflecting an eventual phase of hypovigilance.

PMID- 9615285
TI  - Local administration of serotonin agonists blocks light-induced phase advances of
      the circadian activity rhythm in the hamster.
AB  - Circadian rhythms in mammals are synchronized to environmental light-dark cycles
      through a direct retinal projection to the suprachiasmatic nucleus (SCN), a
      circadian clock. This process is thought to be modulated by other afferents to
      the SCN, including a dense serotonergic projection from the midbrain raphe.
      Previous work from this laboratory demonstrated that a systemically administered
      5-hydroxytryptamine1A/7 (5-HT1A/7) agonist 8-hydroxy-2-(di-n-propylamino)tetralin
      (8-OH-DPAT) dose dependently attenuates light-induced phase shifts of the
      circadian activity rhythm of the Syrian hamster. In this study, we demonstrate
      that local injections (1-100 microM) of the 5-HT1A/7 agonists 8-OH-DPAT or 5
      carboxamidotryptamine into the region of the SCN inhibit light-induced phase
      advances of the circadian wheel-running rhythm. In addition, the inhibitory
      effects of systemically administered 8-OH-DPAT were unaffected by either
      radiofrequency-induced lesions of the intergeniculate leaflet or 5,7
      dihydroxytryptamine-induced lesions of serotonergic projections to the SCN. These
      findings support a modulatory role of serotonin in photic regulation of circadian
      phase through an action at the level of the SCN.

PMID- 9615287
TI  - Behavior of SCN-lesioned chipmunks in natural habitat: a pilot study.
AB  - The necessity of a circadian pacemaker, the suprachiasmatic nuclei (SCN), for
      survival was evaluated in a population of approximately 65 wild eastern
      chipmunks, Tamias striatus. The research involved over 3000 h of field-work
      between May 1995 and October 1997 on a study site at Mountain Lake Biological
      Station, Virginia. The 28 chipmunks randomly designated as project animals
      included 10 SCN-lesioned chipmunks, 5 surgical controls (sham-lesioned), and 13
      intact controls. Visual observation, live trapping, and radio telemetric tracking
      were used to assess 6 aspects of survival and reproduction. Upon release after
      surgery, every animal returned to its den site and was able to maintain its home
      territory. In warm months from May through October, all chipmunks were active
      above ground with a strictly day-active pattern. During the remaining cold
      months, they were normothermic but relatively torpid in their underground dens
      for extended periods of time. Short-term mortality for the initial 3 months
      included only a single intact control chipmunk; loss for the extended period from
      August 1995 to October 1996 was 40% for the SCN-lesioned animals, 0% for surgical
      controls, and 15.4% for the intact controls. Survival differences were not
      significant between surgical control and intact control groups but were
      significant (alpha = .10) between SCN-lesioned and pooled control groups. Annual
      body weight patterns were similar for both groups. Most individuals in both SCN
      lesioned and control groups were reproductively active in the spring and fall
      breeding periods. Lack of major differences may be attributable to the
      exceptionally favorable conditions for survival such as a very abundant fall
      acorn crop, medium population size, and absence of heavy predation.

PMID- 9615286
TI  - Isolation and chronobiological analysis of a neuropeptide pigment-dispersing
      factor gene in Drosophila melanogaster.
AB  - In this article, the authors isolate a gene encoding a neuropeptide in Drosophila
      melanogaster. The substance is called pigment-dispersing factor (PDF), based on
      one of the roles it plays in crustaceans (the arthropods in which this factor was
      initially discovered). The PDF-encoding Drosophila gene (pdf) is intronless and
      present in a single copy per haploid genome. The cytological location of pdf is
      97B on the third chromosome. The putative 102-amino-acid precursor (prepro-PDF)
      consists of a signal peptide and a PDF-associated peptide, followed by the mature
      PDF. The PDF-associated peptide region of the precursor is highly diverged from
      those of the crustacean precursors, whereas the primary structure of the mature
      PDF is conserved in other members of the pigment-dispersing hormone family. A
      single pdf transcript (ca. 0.8 kb) is expressed predominantly in the head; the
      expression levels of pdf mRNA are consistently higher in males than in females.
      Putative pdf homologous transcripts are present in other Drosophila species,
      which exhibit similar sexual dimorphic expression patterns. Cyclic expression of
      pdf over the course of the day and night was assessed, but the mRNA exhibited at
      best very gentle cycling. The pdf expression in two behaviorally arrhythmic
      mutants were examined; the expression was intact in a period0 mutant but absent
      in the disconnected mutant.

PMID- 9615289
TI  - Photoperiod, ambient temperature, and food availability interact to affect
      reproductive and immune function in adult male deer mice (Peromyscus
      maniculatus).
AB  - Winter is often stressful. Increased energetic demands in winter and concurrent
      reductions in energy availability can lead to an energetic imbalance and
      compromise survival. To increase the odds of surviving winter, individuals of
      some nontropical rodent species have evolved mechanisms to enhance immune
      function in advance of harsh winter conditions. Short day lengths provide a
      proximate cue for enhancement of immune function, an adaptive functional response
      to counter environmental stress-induced reduction in immune function. In the
      present study, photoperiod, ambient temperature, and food availability were
      manipulated and reproductive function and cell-mediated immunity were assessed in
      adult male deer mice (Peromyscus maniculatus). Mice maintained in short days
      regressed their reproductive systems and displayed enhanced immune function
      compared to long-day animals. Reduced food availability elevated corticosterone
      concentrations and suppressed reproductive and immune function, whereas ambient
      temperature alone had no effect on cell-mediated immunity. The suppressive effect
      of food restriction on reproductive and immune function was overcome by
      maintaining animals in short days. However, short-day, food-restricted mice
      maintained at low ambient temperatures displayed reduced reproductive and immune
      function compared to animals maintained at mild temperatures. Taken together,
      these results suggest that short-day enhancement of immune function can
      counteract some, but not all, of the immunosuppressive effects of winter
      stressors. These data are consistent with the hypothesis that immune function is
      enhanced in short days to counteract stress-mediated immune suppression occurring
      during winter.

PMID- 9615288
TI  - Exogenous melatonin enhances cell-mediated, but not humoral, immune function in
      adult male deer mice (Peromyscus maniculatus).
AB  - Many nontropical rodent species display seasonal changes in reproductive
      physiology and metabolism, as well as in immune function. Field studies of
      seasonal changes in immune function typically report decreased immune function in
      the short days of winter compared to summer; presumably, reduced immunity in
      winter reflects increased glucocorticoid secretion in response to environmental
      stressors. In contrast, laboratory studies of photoperiodic changes in immunity
      invariably demonstrate increased immune function in short compared to long days.
      Although the precise mechanisms regulating short-day enhancement of immune
      function are not known, it is hypothesized that increased immunity is due to the
      increased duration of melatonin secretion in short compared to long days.
      However, melatonin can act both directly (i.e, via melatonin receptors located on
      lymphatic tissue) and indirectly (i.e., via alterations in gonadal steroids) to
      affect immune function. The present study examined the effects of exogenous
      melatonin administration on both cell-mediated and humoral immune function in
      adult male deer mice (Peromyscus maniculatus), as well as the role of gonadal
      steroid hormones in mediating these effects. Mice either were castrated to remove
      circulating androgens or received sham operations and were implanted with empty
      capsules or capsules containing melatonin. Individual mice implanted with
      melatonin underwent reproductive regression and displayed enhanced splenocyte
      proliferation to the T-cell mitogen concanavalin A; antigen-specific serum
      immunoglobulin M production was unaffected by melatonin treatment. Castration had
      no effect on either cell-mediated or humoral immune function. Taken together,
      these results suggest that exogenous melatonin enhances cell-mediated, but not
      humoral, immune function in adult male deer mice and that this effect is
      independent of gonadal steroid hormones. These results are consistent with a
      direct effect of melatonin on immunity.

PMID- 9615290
TI  - Release of drugs from polymeric hydrogels.
AB  - Hydrogels were prepared from 2-hydroxyethyl methacrylate and ethylene glycol
      dimethacrylate as cross-linking agent. Two different polymerization techniques
      were followed, namely bulk polymerization initiated by dibenzoyl peroxide and
      solution polymerization, in water, using a redox initiator system. Differences in
      the water desorption from swollen samples between the two types of the above
      products were recorded and attributed to the fact that those hydrogels were
      obtained in glassy or rubbery state, according to the polymerization technique.
      Also, the delivery of salicylic acid from samples of the above types was studied,
      and a faster release with higher ultimate delivery was displayed by the solution
      polymerization hydrogels.

PMID- 9615291
TI  - Comparative complement activation study of polypropylene hollow fibres of two
      different makes in static condition.
AB  - The complement activation is one of the major problems encountered in the use of
      extracorporeal devices. The complement-activating potential of two polypropylene
      hollow fibres (used in membrane oxygenator) of different make and designated as
      F1 and F2 was tested with time (10, 30, and 180 minutes). The fibres were brought
      in contact with human blood under in vitro static condition for the comparison. A
      direct measurement of unadsorbed concentration of the complement protein, C3,
      present in the liquid phase of human blood before and after the contact with
      polymer was made using human C3 antisera. This gave a measure of C3 adsorption on
      the fibres with time and probably also gave an indirect measure of C3a in the
      blood. IgG was also estimated using antisera of human IgG. The total protein and
      albumin concentration were measured to obtain an overall adsorption profile of
      these protein on the fibre surfaces with respect to time. The results showed that
      C3 adsorption was taking place mainly through the alternative pathway over and
      above the classical one, being more in the case of F2 than F1. SEM studies
      revealed poor adhesion of platelets on both fibres, though some activated
      platelets were also seen with slight deformation at 10 minutes and a few with
      prominent pseudopodia formations at a later time period on the surface of both
      fibres. The total protein adsorption was faster, and the surface pores of the F1
      were found masked at 10 minutes observation. Later, desorption occurred making
      the pores visible at 180 minutes. The F2 surface examination showed a continuous
      deposition of protein layers with time, thereby masking the pores at 180 minutes.
      The present experimental finding and assessment favoured the F1 as a marginally
      better candidate to be considered for oxygenator development.

PMID- 9615292
TI  - Review of cardiovascular devices.

PMID- 9615293
TI  - The health attitudes of young Hispanic women and the health status of their
      children on the Texas-Mexico border.
AB  - In this paper our objective was to identify child health problems as observed by
      young Hispanic mothers living along the Texas-Mexico border. Samples of 300 young
      Hispanic women living in each of the twin cities of El Paso and Juarez were
      interviewed regarding their knowledge, attitudes, and experiences with respect to
      birth control, pregnancy, maternal and child health, and health care services.
      Only 35 women in El Paso and 50 in Juarez were ever pregnant and their attitudes
      toward health issues were compared to the never pregnant women. Those with living
      children were also asked about the health problems they had observed in their
      children. The results indicate that the ever pregnant women were more positive
      toward both family planning and child bearing than were their never-pregnant
      peers. The ever-pregnant women were also less confident in family planning
      techniques. The mothers in Juarez generally reported more observed illness
      symptoms in their children than did the El Paso mothers.

PMID- 9615294
TI  - The health insurance puzzle: a new approach to assessing patient coverage
      preferences.
AB  - Previous studies of preferences for health insurance benefits have required
      individuals to make a series of complex and repetitive decisions, and have
      assumed that all insured benefits are desirable. This study reports the
      development and testing of a simple, innovative instrument to measure preferences
      for health insurance benefits. The newly developed instrument (Puzzle) is
      designed to allow subjects to select health benefits in a way that underscores
      the trade-offs dictated by budgets and costs. A "puzzle-like" frame representing
      budget constraints and "puzzle piece" benefit cards proportionately sized to
      represent the premium price of a single year's coverage comprise the instrument.
      In a comparison procedure (Money Game), participants "purchase" individual
      benefits by exchanging "play" money for benefit tokens. The Puzzle's utility was
      assessed by examining the convergence of results from both instruments and the
      subject's ratings of and preference for the instruments. One hundred five elderly
      Medicare enrollees seen in the general Internal Medicine outpatient clinic of a
      major southeastern teaching hospital were interviewed. Subjects answered
      interviewer-administered questionnaires and completed both the Puzzle and the
      Money Game. Both McNemar's test and Kendall's tau-b indicated a high degree of
      concordance between benefit choices made using the two instruments. Descriptive
      statistics demonstrated that the Puzzle was clear, easy to use, understandable,
      and preferred to the Money Game. The results suggest that the Puzzle is a
      promising tool for assessing health insurance coverage preferences under
      circumstances of limited expenditures, which can be modified for use with various
      populations who face limited insurance benefits.

PMID- 9615295
TI  - Using the health belief model to explain clinic appointment-keeping for the
      management of a chronic disease condition.
AB  - Broken appointments have untoward repercussions for patients' health and well
      being. Although the literature on missed appointments has been largely
      atheoretical, several studies have tested the Health Belief Model (HBM) in this
      context. Those studies have found HBM dimensions are not predictive of keeping
      appointments for the management of a chronic condition. Given several limitations
      that characterize these studies, questions can be raised about the validity of
      this conclusion. This study investigated the utility of HBM for explaining
      appointment-keeping for Systemic Lupus Erythematosus (SLE), a potentially fatal
      chronic disease. A questionnaire, operationalizing HBM dimensions and exhibiting
      acceptable psychometric properties, was developed for this research and
      administered to 153 SLE patients enrolled at an outpatient clinic of a major
      teaching hospital. In addition to measuring intention to keep appointments, data
      were abstracted from medical records regarding actual appointment-keeping during
      12 months prior to and 6 months following questionnaire completion. Regression
      analysis indicated that general health motivation and perceived severity of SLE
      were uniquely associated in the theoretically predicted direction with,
      respectively, intent and the percentage of scheduled appointments kept (PSAK)
      during the 12 month retrospective period. Perceived costs was associated in the
      expected direction with intent, 12 month retrospective and 6 month prospective
      PSAK. Typical of HBM research the effect sizes uncovered were modest in
      magnitude. Questions for future investigation are discussed.

PMID- 9615296
TI  - Assessing health in an urban neighborhood: community process, data results and
      implications for practice.
AB  - This article examines the community process and data results of a health
      assessment conducted in an urban neighborhood of a middle-size city in Western
      Massachusetts. It describes the four-stage development process of the Health
      Assessment Project (HAP), a collaboration of the UMASS School of Public Health
      faculty and students, community based organizations and youth residents: (1)
      planning with a contemporary participatory approach, (2) implementing the data
      collection with traditional survey methodology, (3) tailoring the data analysis
      for a presentation at a community forum and report, and (4) incorporating the
      community's reaction to data results. In addition, it presents selected data
      results on health conditions of individual household members and perceived
      community health concerns and resources. Salient data results include high rates
      of chronic health conditions such as asthma and other respiratory problems among
      residents 0-18, back pain and other musculoskeletal among younger adults 19-54,
      and high blood pressure and other cardi-circulatory problems among older adults
      age 55 and older. The three most prevalent perceived community concerns are
      substance abuse, gangs and drug dealing. Identified community resources include
      sources of (1) providers of primary care, (2) health information as
      family/friends and Spanish media, (3) social activity such as churches and
      schools. Finally, this paper concludes by discussing implications for community
      health practice.

PMID- 9615297
TI  - The insanity plea in early nineteenth century America.
AB  - In 1846, former New York State Governor William H. Seward defended two murderers
      using the insanity plea in both cases. Seward contended that the accused became
      insane due to brutal beatings administered while they were in the Auburn
      penitentiary. In the William Freeman trial, nine physicians testified that the
      murderer was insane while eight said he was sane. Juries convicted both
      prisoners; one was hanged and the other died in prison awaiting a new trial.
      Seward's legal defense attracted much attention to the jurisprudence of insanity
      and to insanity in general.

PMID- 9615298
TI  - The use of complementary/alternative medicine for the treatment of asthma in the
      United States.
AB  - Despite our advances in the diagnosis and treatment of asthma, the incidence of
      mortality is increasing in developed countries. As patients and health care
      providers seek new options for the treatment and prevention of asthma, various
      complementary and alternative medical therapies are being used. With funding from
      the Office of Alternative Medicine, National Institutes of Health, our goal was
      to identify the type and prevalence of complementary and alternative treatments
      for asthma in use in the United States in order to establish a research agenda
      for the study of the most promising therapies. A survey was developed by an
      expert panel. After undergoing a preliminary round of testing and improvement,
      the survey was then sent along with a postage-paid return envelope as inserts in
      the May 1996 issue of Alternative Therapies in Health and Medicine, a peer
      reviewed periodical of complementary and alternative medical research and
      scholarly activity; 10,000 surveys were distributed. We asked that only those who
      treated asthma respond. The surveys were designed to identify characteristics of
      the respondent, their particular practice type, use of complementary and
      alternative medicine, or conventional medicine in general, patient
      characteristics and numbers, and their use of 20 specific potential therapies to
      treat asthma. A total of 564 surveys were returned. The 5.64% response rate was
      low but was reflective of the demographics of the readership of this journal of
      complementary and alternative medicine. The survey population was 46% male and
      43% female; 11% did not specify gender. They ranged in age from under 31 years
      old to over 70. The largest group (37%) of respondents held degrees as medical
      doctors, 27% held doctorates in complementary and alternative medicine related
      disciplines, 11% had registered nursing degrees, 4% were acupuncturists and 18%
      did not specify their training. Practice characteristics between MD and non-MD
      asthma care providers did not differ. The majority had general practices (75%)
      seeing all ages of patients. MDs were less likely to employ complementary and
      alternative medicine techniques for asthma compared to non-MDs. Both groups
      identified dietary and nutritional approaches as their most prevalent and useful
      asthma treatment option. Use of botanicals, meditation and homeopathy were
      frequently cited; statistically significant differences appeared in the rankings
      of treatment usefulness and prevalence between MD and non-MDs. Non-MD asthma care
      providers were more likely to ask patients about their use of complementary and
      alternative treatments for asthma than MDs (92% vs. 70%), while both groups
      showed statistically significant increases in their levels of patient inquiries
      compared to 2 years previously (up 9% and 8% for MDs and non-MDs respectively).
      The predominance of diet and nutrition supplementation used by MDs and non-MDs
      suggests that further attention and research efforts should be directed toward
      this area of complementary and alternative practice. Other complementary and
      alternative medicine practices such as botanicals, meditation and homeopathy
      appear to warrant research efforts. Differences between MDs and non-MDs in their
      use of such therapies may reflect different philosophies as well as training.

PMID- 9615299
TI  - Kiwi allergens and their cross-reactivity with birch, rye, timothy, and mugwort
      pollen.
AB  - In order to study kiwi allergens and examine their cross-reactivity to birch,
      rye, timothy, and mugwort pollen, immunoblot and enzyme immunoassay (EIA)
      inhibition tests were performed with self-prepared kiwi extract. For the
      investigations, the sera of 22 kiwi-allergic patients were used, which were
      characterized by radioallergosorbent (RAST) measurements for kiwi, birch pollen,
      and apple with commercial allergen disks. The RAST values for kiwi were compared
      with those obtained by self-prepared kiwi extract disks. In the RAST, the
      allergen potency of this extract was found to be very similar to that of the
      commercial extracts. This extract was able to bind immunoglobulin E from kiwi
      allergic patients in the immunoblots and EIA. Immunoblot results revealed a broad
      spectrum of IgE specificities; 12 allergens were identified within the range of
      15 to 94 kDa, 10 of which cross-reacted with birch, timothy, rye, and mugwort
      pollen, while two (25 and 30 kDa) were not inhibited homologously or by pollen.
      EIA inhibition additionally revealed kiwi-specific allergens. Three proteins of
      the kiwi extract (25, 30 and 43 kDa) were considered to contain a carbohydrate
      moiety. Profilin seems to be relevant in cross-reactivity of kiwi allergens.

PMID- 9615300
TI  - Pollen, mite and mould samplings by a personal collector at high altitude in
      Nepal.
AB  - The new personal portable sampler for detection of environmental biologic
      particles (Partrap FA52, Coppa, Biella, Italy) was used to evaluate both
      atmospheric and indoor biologic particles in bedding at high altitudes during two
      Italian scientific expeditions in Nepal, in 1994 and 1996 respectively. The
      sampling was performed outdoors and indoors at the following altitudes: Katmandu
      1,330 meters (m), LuKla 2,800 m, Namche 3,500 m, Pericle 4,200 m and Piramide
      5,050 m. In both expeditions each sample of outdoor and indoor air was obtained
      by sucking air into the sampler either against the wind during a 6-h period, from
      9 am to 3 pm, or from bedding of inhabitants resident at the different altitudes
      for 5 min. The number of pollens, moulds and mites trapped in each sample were
      assessed. The statistical analysis of the results by Spearman correlation test
      revealed a significant inverse correlation (p < 0.02) between altitude and the
      number of the considered biologic particles for sampling carried out during both
      the 1994 and 1996 expeditions. Moreover, Wilcoxon paired test showed no
      significant difference between the biologic sampling obtained in the two
      expeditions. These results confirm the decrease of the environmental biologic
      charge in relation to the increase of altitude and prove the efficacy of Partrap
      FA52 in obtaining reproducible quantitative data.

PMID- 9615301
TI  - Daily variation patterns of airborne allergenic pollen in southwestern Spain.
AB  - The study was carried out using a Burkard sampler installed on the roof terrace
      of the School of Pharmacy, Seville, for two years (1995 and 1996). Eight pollen
      types described in the literature as having allergenic activity were chosen. They
      were Poaceae, Olea europaea, Chenopodiaceae/Amaranthaceae, Plantago, Rumex,
      Urticaceae (including Parietaria), Cupressaceae, and Platanus hispanica. The
      types were grouped according to the similarity of their pattern of intradiurnal
      variation in pollen concentration. The following associations were established by
      multivariate analysis: Urticaceae and Chenopodiaceae/Amaranthaceae (appearing
      mainly between 11:00 and 20:00), Olea europaea and Plantago (12:00 to 19:00),
      Poaceae and Rumex (appearing throughout the day), and Cupressaceae and Platanus
      hispanica (8:00 to 14:00). The patterns of intradiurnal variation were similar
      both years for each type, despite the fact that the two years were
      climatologically different (1995 was dry and 1996 wet). We conclude that these
      behavior patterns are endogenous to the plants, and are hardly affected by
      meteorological parameters.

PMID- 9615302
TI  - Bacterial lipopolysaccharide-induced sulfidoleukotriene release from peripheral
      blood leukocytes in patients with asthma and chronic obstructive pulmonary
      disease.
AB  - Bacterial endotoxins are seen to possess strong proinflammatory activities. These
      substances may intensify inflammation in the airways of patients with chronic
      obstructive pulmonary disease (COPD) and asthma by facilitating release of
      various mediators from different types of cells. Sulfidoleukotrienes (sLT) cause
      bronchoconstriction, increase vascular permeability and stimulate mucous
      secretion. The aim of our study was to evaluate sLT release from peripheral blood
      leukocytes stimulated by Klebsiella pneumoniae lipopolysaccharide (LPS) and
      obtained from COPD and asthma patients. Nineteen subjects with mild or moderate
      stable bronchial asthma, nine patients with COPD and 10 healthy controls entered
      the study. Cellular allergen stimulation test (CAST)-ELISA test was performed
      using Buhlmann Laboratories AG kits to determine sLT production. The differences
      between atopic (462.57 SD = 215.89 pg/ml) and nonatopic (474.25 SD = 158.02
      pg/ml) asthmatics in comparison to healthy controls (191.55 SD = 53.2 pg/ml) were
      statistically significant (p < 0.005) upon LPS stimulation at the concentration
      of 10 micrograms/ml. At lower LPS concentration (1 microgram/ml) the difference
      was statistically significant only between nonatopic asthmatics and healthy
      subjects (p < 0.02). In the COPD group the sLT production in either LPS
      concentration was higher than in the controls but the difference was not
      significant. We suppose that leukocytes obtained from asthmatics and COPD
      patients are more susceptible to LPS than these cells from healthy individuals.
      An increased sLT production upon LPS stimulation during respiratory bacterial
      infection may intensify inflammation, bronchoconstriction and increase
      nonspecific bronchial hyperreactivity.

PMID- 9615303
TI  - The effect of house dust mite specific immunotherapy on cysteinyl leukotriene
      production by blood leukocytes in subjects with perennial allergic rhinitis and
      asthma.
AB  - Specific immunotherapy has been successfully used in the treatment of allergic
      diseases for years. In this study, we examined the clinical efficacy of specific
      immunotherapy and its effect on cysteinyl leukotriene releasability by blood
      leukocytes in house dust mite allergic subjects with asthma and allergic
      rhinitis. In an open, parallel study, 13 subjects were treated with specific
      immunotherapy for 12 months and five patients served as the control group. Before
      specific immunotherapy treatment, and 1 and 12 months after, patients were
      evaluated with respect to total immunoglobulin (Ig) E levels, Dermatophagoides
      pteronyssinus specific IgE levels, symptom scores, usage of rescue medicines,
      lung function tests, nasal challenge scores, skin reactivity to D. pteronyssinus
      and cysteinyl leukotriene releasability by blood leukocytes. At the 12th month of
      specific immunotherapy, total asthma symptom scores, bronchodilator requirement,
      number of sneezes following nasal challenge and immediate skin reactivity to D.
      pteronyssinus was decreased, while FEV1 increased compared to the pretreatment
      values (p < 0.05 for each). These parameters remained unchanged in the control
      group. In vitro cysteinyl leukotriene releasability by blood leukocytes in
      response to D. pteronyssinus antigen and anti-IgE antibody remained unchanged
      both in the specific immunotherapy group and the control group. However, in the
      treated group, there were six patients who showed at least a 50% reduction in
      their symptoms after specific immunotherapy. In five of these, cysteinyl
      leukotriene release induced by both HACM buffer and D. pteronyssinus were
      decreased by more than 50% of the baseline values. The other patient demonstrated
      only a marked decrease (more than 50%) in background. Our results suggest that
      specific immunotherapy is effective in the treatment of allergic rhinitis and
      bronchial asthma due to house dust mite allergy and that the clinical response to
      specific immunotherapy may be associated with decreased cysteinyl leukotriene
      releasibility by blood leukocytes in some patients.

PMID- 9615304
TI  - Circulating adhesion molecules in bronchial asthma.
AB  - It has been shown that leukocyte adhesion mechanisms play an important role in
      the development of allergic inflammation in bronchial asthma. We measured the
      circulating levels of E-selectin (formerly called sElam-1) and intercellular
      adhesion molecule-1 (ICAM-1) by ELISA in asthmatic subjects. We selected 10
      asthmatic subjects to study during an asthma attack, 10 asthmatic subjects in an
      intercrisis phase, and 20 healthy nonatopic control subjects. A significant
      increase in the serum levels of soluble E-selectin and soluble ICAM-1 was found
      in the group of patients during an asthmatic crisis compared to the controls (p <
      0.001). The asthmatic patients in an intercrisis phase and the healthy control
      subjects had overlapping levels of soluble ICAM-1 and soluble E-selectin. The
      clinical utility of serum soluble levels of adhesion molecules has not been
      completely assessed and these circulating molecules do not appear to be a useful
      marker for monitoring the persistent inflammatory activity in stable bronchial
      asthma.

PMID- 9615305
TI  - Lymphocyte subpopulations, cytokine release and specific immunoglobulin G in
      reactive and nonreactive beekeepers.
AB  - Although bee venom sensitization and systemic sting reactions are common among
      beekeepers, the prediction of the severity of reactions has not yet been possible
      with laboratory tests. The present study was designed to evaluate parameters that
      might be clinically useful in estimation of systemic reactivity, and parameters
      that could differentiate allergic beekeepers from sensitized subjects. Thirty-two
      beekeepers were selected and placed into the following three groups: anergic (n =
      10), asymptomatic sensitized (n = 11), and allergic (n = 11). Peripheral blood
      lymphocyte subpopulations, venom-specific immunoglobulin (Ig) E and IgG and
      cytokine release by peripheral blood mononuclear cells were measured. The ratio
      of stimulated interleukin-4 to stimulated interferon-gamma was significantly
      higher in sensitized beekeepers than in allergic or anergic subjects. Venom
      specific IgG correlated significantly with the number of annual stings (r =
      0.575) and the years spent in beekeeping (r = 0.471). No significant differences
      in the subpopulations of peripheral blood lymphocytes were found between the
      study groups. We conclude that differences in the subpopulations of peripheral
      blood lymphocytes are not associated with sensitization or systemic reactivity.
      In asymptomatic sensitized beekeepers, T helper 2 T-cell dominance is more
      pronounced than in allergic subjects. Bee venom specific IgG correlates directly
      with the degree of exposure to bee venom.

PMID- 9615306
TI  - Assessment of the bronchodilator effect of inhaled furosemide compared to
      salbutamol in asthmatic patients.
AB  - To compare the bronchodilator effects of high-dose inhaled furosemide, we studied
      80 patients who were nonsmokers presenting some degree of bronchial obstruction.
      Of these patients, 40 were given salbutamol (1%) aerosol and the remaining 40
      were given furosemide aerosol (100 mg). Respiratory functional tests were
      conducted at 10 min and 30 min, as well as measurement of pulse and blood
      pressure. Patients in the salbutamol group showed an improvement in forced
      expiratory volume (FEV1) of 7.9% at 10 min and 30 min, and the group given
      furosemide improved 6.9% (p > 0.05). Systolic blood pressure showed a slight
      increase of 2 mmHg in the salbutamol group and a decrease of 6 mmHg in the
      furosemide group (p < 0.05). The same occurred for diastolic blood pressure (p <
      0.05). Pulse increased from 73.7 to 75.2 beats per min in the salbutamol group;
      however, in the furosemide group, pulse declined from 73.7 to 71.8 beats per min
      (p < 0.05). We conclude that furosemide at a dose of 100 mg has the same
      bronchodilator effect as salbutamol, as measured by FEV1 and forced expiratory
      flow of 25% to 75%. Furosemide was also related with a mild hypotensive effect
      and drop in pulse.

PMID- 9615307
TI  - Reactive airways dysfunction syndrome: two case reports.
AB  - Reactive airways dysfunction syndrome (RADS) is a type of asthma that develops in
      subjects without prior pulmonary disease, following single or multiple exposure
      to high levels of nonimmunogenic irritants. The main difference from classic
      occupational asthma is the absence of a latency period. Non-specific bronchial
      hyperresponsiveness is characteristic of the disease and usually persists after
      cessation of exposure. We report the cases of two subjects in whom RADS developed
      after occupational exposure to irritants.

PMID- 9615308
TI  - The relationship between clinical efficacy of specific immunotherapy and serum
      intercellular adhesion molecule-1 levels.
AB  - The intracellular adhesion molecule-1 (ICAM-1) is a reliable marker of allergic
      inflammation; its soluble isoform in serum is hypothesized to reflect the
      severity of the disease, therefore it may be used to monitor the efficacy of
      specific immunotherapy. We evaluated the levels of soluble ICAM-1 in the serum of
      14 patients with grass-induced respiratory allergy before and after 12 months of
      specific immunotherapy, and correlated this parameter with the clinical outcome,
      measured using a visual analog scale. We found that in the majority of the
      patients, soluble ICAM-1 levels paralleled the clinical trend of the disease,
      with a significant decrease of soluble ICAM-1 in patients with successful
      specific immunotherapy (Spearman's correlation test: r = 0.57; p < 0.001).
      Therefore, we hypothesize that soluble ICAM-1 could be regarded as a reliable
      indirect marker of specific immunotherapy efficacy and that it could be used for
      monitoring clinical outcome.

PMID- 9615309
TI  - Allergenic sesquiterpene lactones from Eupatorium cannabinum L. and Kaunia
      rufescens (Lund ex de Candolle).
AB  - From Eupatorium cannabinum L., a hitherto unknown alpha-methylene-gamma
      butyrolactone, 3 beta-peroxyeucannabinolide, was isolated. This compound and
      eupatoriopicrin from the same plant showed a weak sensitizing capacity in guinea
      pigs. 2-oxoludartin and dehydroleucodin, isolated from Kaunia rufescens (syn.
      Eupatorium rufescens), were strong sensitizers in the same sensitizarian
      procedure.

PMID- 9615310
TI  - Fungitoxic activity of some cytochalasins and their derivatives on Phytophthora
      species.
AB  - The activity of cytochalasin B was tested on 8 Phytophthora species, while the
      same toxin, some of its derivatives and natural analogues, namely cytochalasin F
      and deoxaphomin, were assayed at 2 x 10(-5) - 2 x 10(-4) M on the most sensitive
      species, P. cactorum. A significant inhibitory activity on P. cactorum was shown
      by cytochalasin B, its 7-monoacetyl derivative, and deoxaphomin. The hydroxy
      group at C-20 and the conformational freedom of the macrocyclic ring proved to be
      important structural features for this activity. The 7-hydroxy group at C-7
      appeared to have no influence on this toxicity, while a size reduction associated
      with the carbocyclic nature of the macrocycle seems to lightly increase the
      activity. The 7-O-acetylcytochalasin B showed selective toxic activity on P.
      cactorum at the tested concentration, thus suggesting a possible use as a
      fungicide for this compound.

PMID- 9615311
TI  - Toxic effects of deoxynivalenol on ribosomes and tissues of the spring wheat
      cultivars Frontana and Casavant.
AB  - The toxic effects of the Fusarium graminearum trichothecene toxin deoxynivalenol
      were determined on ribosomes and leaf tissues of the fusarium head blight
      resistant spring wheat cultivar Frontana and the susceptible spring wheat
      cultivar Casavant. The use of a poly-U-directed 14C-phenylalanine and
      deoxynivalenol ribosome-binding assays provided evidence of resistance to the
      protein-synthesis inhibition effects of deoxynivalenol in the head blight
      resistant cultivar Frontana. This is probably due to the existence of a mutation
      in the peptidyl transferase. This cultivar also exhibited resistance to the
      membrane-damaging properties of this toxin compared to the other cultivar. This
      report summarizes the evidence for various kinds of "trichothecene tolerance"
      mechanisms in fusarium head blight-resistant wheat genotypes.

PMID- 9615312
TI  - Influence of dietary nivalenol exposure on gross pathology and selected
      immunological parameters in young pigs.
AB  - Young pigs were fed diets to which 0, 2.5, or 5 mg/kg of purified nivalenol (NIV)
      had been added. The exposure continued for 3 weeks without any signs of feed
      refusal, vomiting, or change in clinical appearance, and there were no changes in
      body or organ weights due to the exposure. However, the concluding macroscopic
      examination revealed gastrointestinal erosions and signs of nephropathy in most
      of the exposed pigs. There were no differences in total or differential blood
      leukocyte counts between control and exposed pigs in blood samples collected
      after 0, 1, or 3 weeks, nor in the number of thymocytes at the end of the trial.
      Spleen cell numbers showed a dose-dependent decrease after 3 weeks of exposure
      that was statistically different from controls in pigs exposed to 5 mg NIV/kg.
      Flow cytometric analysis of lymphocytes revealed decreased numbers of both the
      CD4+ and the CD8+ subpopulations in the spleen at this point in time, reflecting
      the lower numbers of splenocytes; but no proportional changes were seen. In
      blood, exposure to NIV caused a transient decrease in the proportion of CD4+
      cells after 1 week of exposure. Analysis of IgG and IgA in plasma showed a time
      dependent tendency of increasing plasma concentrations of IgA and decreasing
      concentrations of IgG in the 2.5 mg/kg group, but differences in Ig levels
      between experimental groups and controls were not observed at any time. No
      differences were seen in the mitogen-induced proliferation by lymphocytes from
      blood, spleen, or thymus. In conclusion, exposure of young pigs to NIV in the
      diet caused pathological alterations in the kidneys and gastrointestinal tract
      and reduced the number of splenocytes. The results also indicated that exposure
      to NIV caused a time-dependent increase in IgA production in the 2.5 mg/kg group.

PMID- 9615313
TI  - First identification of microcystins in Irish lakes aided by a new derivatisation
      procedure for electrospray mass spectrometric analysis.
AB  - Recent animal and bird deaths at several lakes in Ireland were indicative of
      possible cyanobacterial poisoning. Using protein phosphatase inhibition assays,
      microcystins (MCs) were identified in extracts of cyanobacteria from several
      lakes at concentrations ranging from 1.6 to 168 micrograms/g. This is the first
      report of MCs in Irish freshwaters. The protein phosphatase inhibition assay was
      used to screen fractions during HPLC purification of the MCs in cyanobacteria
      (Anabaena and Oscillatoria) and water samples from Corbally and Caragh Lakes. MC
      LR, MC-HtyR, MC-FR, and MC-YR and 3 unidentified MCs of m/z values 1028.5, 981,
      1042.7 were isolated from the Corbally sample; while the Caragh Lake sample
      contained largely MC-LR and MC-YR. A new microanalytical technique was developed
      for the confirmation of MCs which involved the derivatisation of the
      methyldehydroalanine group of MCs with 2-aminoethanethiol. Electrospray mass
      spectrometry of these products showed characteristic double-charged ions, and
      this novel technique was useful for differentiating MCs from co-eluting
      impurities in HPLC fractions of cyanobacterial extracts.

PMID- 9615314
TI  - Toxicologic evaluation of yessotoxin.
AB  - Yessotoxin (YTX), originally found in association with diarrhetic shellfish
      poisoning (DSP), caused neither intestinal fluid accumulation nor inhibition of
      protein phosphatase 2A. Orally, YTX was not lethal to mice at 1.0 mg/kg. The
      toxin showed weak cytotoxic and antifungal activities. Neither hemolytic nor
      ichthyotoxic effect was observed.

PMID- 9615315
TI  - Why randomize clinical trials?

PMID- 9615316
TI  - Acute promyelocytic leukemia in children.

PMID- 9615317
TI  - Treatment of osteosarcoma 1972-1997: an American perspective.

PMID- 9615318
TI  - Psychiatric symptomatology in adolescents with cancer.
AB  - Adolescents with cancer need to cope with their disease and treatment while
      accomplishing the tasks unique to this developmental period. In this pilot study,
      the prevalence of psychological morbidity among adolescents with cancer was
      examined. In addition, assessment methods and risk factors were explored. Forty
      three recently diagnosed adolescents with cancer completed the Hospital Anxiety
      and Depression Scale (HADS), the Beck Depression Inventory (BDI), and the
      Rotterdam Symptom Checklist (RSCL) and underwent a full psychiatric assessment.
      In the psychiatric interviews, 9% of the sample was diagnosed with a depressive
      mood disorder. Results suggest that self-report rating scales can be useful
      assessment instruments if used as complementary tools. Psychosocial assessment of
      the adolescent with cancer is nevertheless difficult. This appears to be due to
      an atypical symptomatology pattern and a tendency toward the masking of distress.
      Case examination of depressed patients suggests that illness and treatment
      factors may not be primary risk factors for the development of psychological
      morbidity. External stressors such as poor family support and past sexual abuse,
      when compounded by illness and treatment factors, may be more relevant.

PMID- 9615320
TI  - Multidisciplinary management of osteosarcoma: experience in Hong Kong.
AB  - All pediatric osteosarcomas treated in our hospital between 1985 and 1995 were
      reviewed. There were 26 patients, 15 males and 11 females, aged 20 or less at
      diagnosis. All had limb primaries. Nineteen patients had localized disease and
      seven presented with metastases. Intensive multiagent chemotherapy was given both
      pre- and postoperatively. Most patients were treated with the Rosen T10 regimen
      or its modifications. Only one patient had limb salvage surgery; all others had
      amputation. With a median follow-up of 74 months, the 5-year disease-free
      survival among patients with localized disease was 65.2%. Being female and having
      a high 6-hour postinfusion methotrexate level with a median level greater than
      700 mumol/L were good prognostic factors. Three of the seven patients with
      metastatic disease were alive at 21, 26, and 140 months after diagnosis. All of
      them had lung secondaries. Survival rates achieved in our center were comparable
      to those reported in literature. However, our amputation rate was high and
      further development in expertise for limb salvage treatment is a goal.

PMID- 9615319
TI  - The stage I yolk sac tumor of testis in children younger than 2 years,
      chemotherapy or not?
AB  - Yolk sac tumor is the most frequent germ cell tumor of testis in children. For
      stage I yolk sac tumor of testis in children younger than 2 years, high inguinal
      orchiectomy alone has been the standard treatment, with a cure rate of at least
      75%. Here, we compare the treatment results of receiving chemotherapy or no
      chemotherapy after orchiectomy, to analyze the role of chemotherapy. From
      February 1987 to January 1997, 22 children younger than 2 years, with stage I
      yolk sac tumor of testis, were included in the study. All patients had high
      inguinal orchiectomy without retroperitoneal lymphadenectomy. Initial diagnostic
      imaging studies included computed tomographic scan of abdomen, chest radiography,
      and long bone survey. Clinical stage I was defined as a tumor completely resected
      with no evidence of local regional lymph node involvement or distant metastases.
      Serum alpha-fetoprotein (AFP) was assessed at diagnosis. After orchiectomy,
      diagnosis, and staging, patients were stratified into two treatment groups, with
      or without chemotherapy, according to the decision of the parents. Ten children
      received chemotherapy consisting of cisplatin, vinblastine, and bleomycin (PVB,
      modified "Einhorn regimen") for 12 weeks. The remaining 12 patients were followed
      up according to a "wait and see" policy. Determination of AFP was performed
      monthly during the first postoperative year, every other month during the second
      year, every 3 months during the third year, every 6 months during the fourth
      year, and yearly until the fifth postoperative year at least. The duration of
      follow-up ranged from 3 months to 119 months (median, 53 months). The Kaplan
      Meier plot estimated an overall survival rate of 91.6% at 7 years after
      diagnosis. Among the 12 patients without chemotherapy, 2 children had relapses at
      4 and 6 months after diagnosis, respectively. One was cured with PVB
      chemotherapy. The other patient died with refractory lung metastasis, in spite of
      intensive multimodality salvage therapy. The Kaplan-Meier plot showed a survival
      rate of 80% at 7 years and a relapse-free survival rate of 81.8% at 5 years after
      diagnosis. All children receiving chemotherapy were alive and free from relapse.
      There was no significant treatment-related toxicity. Our results may suggest that
      PVB chemotherapy after orchiectomy is an affective and safe regimen for stage I
      yolk sac tumor of testis in children younger than 2 years. Instead of four
      courses of PVB as used here, two or three courses could be enough. To elucidate
      the necessity for chemotherapy and to determine the number of courses of PVB
      needed (if chemotherapy is given), a randomized study of more cases is warranted.

PMID- 9615321
TI  - Genotype-phenotype correlation of sickle cell disease in the United Arab
      Emirates.
AB  - We have identified the beta s-globin gene haplotypes of 85 patients with sickle
      cell disease attending the Dubai Thalassemia Center and assessed the influence of
      haplotype, alpha-thalassemia, and fetal hemoglobin on the clinical presentation.
      Identification of the beta s haplotypes was based on mutation analyses in the
      promoter sequences of the G gamma- and A gamma-globin genes. The Arabian-Indian
      haplotype was found in 52% of the beta s chromosomes, whereas the remaining were
      the Bantu and Benin haplotypes. Those with the Arabian-Indian haplotype in this
      group had a significantly higher fetal hemoglobin (Hb F) level (mean 27%) and a
      milder clinical course. In contrast, those with the African haplotypes, Bantu and
      Benin, expressed relatively lower Hb F levels (mean 11.3%), with a severe
      clinical presentation. Coinheritance of alpha-thalassemia trait in the African
      haplotypes had an ameliorating effect on hemolytic episodes, but vaso-occlusive
      crises were more frequent.

PMID- 9615323
TI  - Prevention of beta-thalassemia major by antenatal screening in Hong Kong.
AB  - The thalassemias are common in Hong Kong. One of the severe forms, beta
      thalassemia major, has been preventable locally by antenatal screening since
      1983. Yet new patients are still being diagnosed. In this retrospective study, 34
      children with severe beta-thalassemia syndromes were diagnosed in two major
      public hospitals between 1990 and 1996. They included one pair of identical twins
      and two pairs of siblings. Twenty-seven (79%) had homozygous beta-thalassemia and
      seven (21%) had beta E thalassemia. All but four (12%) were transfusion
      dependent. Fifty-five (89%) parents had been evaluated for their thalassemia
      status. Forty-eight had beta-thalassemia traits and seven were hemoglobin E
      carriers. The reasons for the birth of these children with severe beta
      thalassemia syndromes were (1) late or no antenatal visit (n = 8, 24.2%),
      including three cross-border deliveries in which the pregnant mothers came from
      mainland China to Hong Kong for confinement, (2) lack of maternal screening (n =
      13, 39.4%), (3) lack of paternal screening (n = 7, 21.2%), (4) parental refusal
      (n = 3, 9.1%), and (5) unknown (n = 2, 6.1%). These findings suggest that several
      factors undermine the effectiveness of antenatal screening for prevention of
      thalassemias. Many medical practitioners and the general public are still not
      aware of the screening procedures. The migration of population from mainland
      China to Hong Kong may result in the birth of many more children with beta
      thalassemia major.

PMID- 9615322
TI  - All-trans-retinoic acid (ATRA): pediatric acute promyelocytic leukemia.
AB  - Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloblastic
      leukemia (AML). In this report, we present the clinical features, management, and
      outcome of pediatric patients with APL treated with all-trans-retinoic acid
      (ATRA). Of 52 newly diagnosed cases of APL between February 1992 and December
      1996, 15 were in the pediatric age group (younger than 15 years). Four patients
      were treated with ATRA alone and 11 were allocated to receive ATRA followed by
      chemotherapy. Eighty-six percent of the patients achieved a complete response.
      The patients who received ATRA alone as maintenance therapy had relapses with a
      median duration of remission of 8 months (range 6-12). The patients who received
      ATRA, followed by consolidation chemotherapy, had a prolonged duration of
      remission, with a median of 20 months (range 13-28). In addition, rapid
      correction of coagulopathy was observed in these patients. The median duration
      for correction of coagulopathy was 7 days (range 5-11) and the median duration
      for recovery from neutropenia after chemotherapy was 10 days (range 7-20). Two
      major side effects of ATRA were hyperleukocytosis and retinoic acid syndrome.
      Significantly prolonged disease-free survival was seen in patients who received
      ATRA with chemotherapy. APL is not uncommon in the pediatric age group. ATRA was
      well-tolerated by these patients. Consolidation with chemotherapy helps in
      prolonging the disease-free survival in patients with APL in comparison to
      treatment with ATRA alone.

PMID- 9615324
TI  - Complete recovery of renal function in a Wilms' tumor patient after acute renal
      failure caused by autologous bone marrow transplantation (ABMT).
AB  - An autologous bone marrow transplantation (ABMT) was carried out on a 4-year-old
      boy following the second pulmonary relapse of a nephroblastoma. Glomerular and
      tubular function of the remaining kidney before ABMT was normal. Etoposide,
      carboplatin, and melphalan were used in the conditioning regimen. The patient
      developed acute renal failure (ARF), and hemodialysis was required for 3 weeks.
      The situation was further complicated by his requiring mechanical ventilation for
      12 days. Today, the patient is in good general health and in stable remission 32
      months after bone marrow transplantation. This report shows that even serious
      tubular and glomerular dysfunction may be completely reversible in children. The
      background for high-dose chemotherapy with ABMT or stem cell rescue is discussed.

PMID- 9615325
TI  - Blue rubber bleb nevus syndrome: a cause for recurrent episodic severe anemia.
AB  - A 7-year-old boy had several episodes of severe anemia, requiring
      hospitalizations and blood transfusions. Skin hemangiomas characteristic of blue
      rubber bleb nevus syndrome were present since infancy, but were not recognized as
      being indicative of simultaneous existence of bowel hemangiomas, resulting in a
      delay of several years before an accurate diagnosis could be made.

PMID- 9615326
TI  - Ki-1 lymphoma with cardiac involvement at initial presentation.
AB  - Anaplastic large cell lymphoma is a rare malignancy in childhood. We describe the
      case of a 6-year-old boy with Ki-1 lymphoma of the thymus who presented with an
      endocardiac mass. The first histologic analysis suggested a high-grade
      undifferentiated sarcoma, but reevaluation and immunohistochemistry confirmed the
      CD30+ lymphoid derivation of the process. The patient was given chemotherapy and
      24 months later he remains in complete remission. It is noted that
      echocardiography was repeated many times to detect heart lesion.

PMID- 9615327
TI  - alpha-Thalassemia and hereditary spherocytosis in the same patient: the
      interaction of two diseases.

PMID- 9615328
TI  - A case of non-Fanconi anemia bone marrow dysfunction with familial involvement.
AB  - We report on a Greek girl with pancytopenia, short stature, clinodactyly, cleft
      palate, exopthalmus, strabismus, cafe-au-lait spots, and mild mental retardation
      in whom chromosomal analysis excluded Fanconi anemia. The occurrence of
      erythroleukemia in the family and the presence of macrocytosis in her father and
      low blood counts in her sister favor the diagnosis of an inherited syndrome of
      familial marrow dysfunction rather than that of a sporadic case.

PMID- 9615329
TI  - Acute lymphoblastic leukemia accompanied by severe hypercalcemia: successful
      treatment including aminohydroxypropylidene bisphosphonate (pamidronate disodium)

PMID- 9615330
TI  - Treatment of uterine bleeding in the adolescent hematology/oncology patient.

PMID- 9615331
TI  - Health promotion: from the generic to specifics.

PMID- 9615332
TI  - The university and the health of children.

PMID- 9615333
TI  - Conditions for health: the Toronto Healthy City Model.

PMID- 9615334
TI  - [Health promotion of the hospitalized child: participatory action research
      approach].

PMID- 9615335
TI  - Using online lists for health promotion.

PMID- 9615336
TI  - Health promotion and health education in Puerto Rico: an overview.

PMID- 9615337
TI  - Health consequences of Chernobyl and other radiation accidents. Report on the
      European Union Cluster Contractors' workshop (San Miniato, Italy, 17-22 June
      1997).
AB  - The Radiation Protection Research Unit of the European Commission has been
      supporting collaborative research projects on the radiological consequences of
      the Chernobyl accident since 1991. However, in the Fourth Framework Programme of
      the Commission which started in 1996, the collaboration with scientists in the
      former Soviet Union has been placed on a different footing, and the programme has
      been expanded to include other regions, especially in Russia and Kazakhstan,
      where previous nuclear incidents have led to the exposure of workers and the
      local populations and to widespread radioactive contamination. There are 15
      projects on health-related studies in the newly started programme, and in order
      to improve the collaboration between the different scientists working in these
      projects a Cluster Contractors' Meeting was organised in San Miniato, Italy, in
      June 1997 with the participation of some 50 scientists from the European Union
      (EU) and the Newly Independent States (NIS). This report summarizes the different
      topics, including molecular biology and treatment of childhood thyroid cancer,
      various epidemiological studies and dose reconstruction, which were discussed at
      the meeting and which form the major projects in the new collaborative programme.

PMID- 9615338
TI  - Lung cancer in nuclear workers of Mayak. A comparison of numerical procedures.
AB  - Lung cancer mortality was analyzed among 4279 nuclear workers of the Mayak
      facilities in the former Soviet Union, who were exposed to chronic irradiation
      both externally and internally from incorporated plutonium. The analysis was
      carried out in terms of a relative risk model. It was shown that an earlier
      estimate of the excess relative risk for lung cancer, that exceeds the value
      employed by ICRP by a factor of roughly 2, as well as an earlier estimated
      latency period of 24 years for lung cancer induction were the result of the
      numerical procedure chosen. In another recently published case control study, a
      purely quadratic, threshold-type dose response to incorporated plutonium was
      deduced. In the present calculations, no evidence for a departure from linearity
      in dose response was suggested. Principal aim of this study has been the
      comparison to methods used in the earlier cohort analysis. More detailed risk
      modelling on the basis of the most recent follow-up will be required.

PMID- 9615339
TI  - Direct beta measurements to determine in vivo whole-body activities of 90Sr in
      residents of the southern Urals: description of a new method.
AB  - For 44 individuals living in areas of the Southern Urals with historical 90Sr
      contamination, whole-body activities of this radionuclide were investigated using
      a new mobile detection system. Beta-particles from 90Sr/90Y decay were measured
      in vivo via two proportional counters mounted in front of the forehead and above
      the head, respectively. In order to correct for absorption by the skin, scalp
      thickness was measured using ultrasonic techniques. Corrections are given with
      respect to self-absorption by the bone matrix and absorption by hair. A procedure
      is described to extrapolate from measured 90Sr activity of the skull bone to
      total 90Sr skeleton burden. As a result, 90Sr whole-body activities of up to 50
      kBq were recorded in the selected cohort. For the same individuals, 90Sr was
      measured via the detection of bremsstrahlung using an established whole-body
      counting device. The overall results of both systems agree within 15%, but
      differences exceeding a factor of 2 were observed in some cases.

PMID- 9615340
TI  - Variability of water content and of depth profiles of global fallout 137Cs in
      grassland soils and the resulting external gamma-dose rates.
AB  - 137Cs from global fallout of nuclear weapon testings in the 1950s and 1960s was
      determined in successive layers (0-30 cm) of eight undisturbed grassland soils in
      Bavaria, Germany. The maximum activity concentration was found in soil layers
      between 4 and 15 cm below the surface. Using the vertical distribution of the
      cesium activity, which varied considerably from site to site, the mean residence
      half-time of 137Cs from global fallout in each soil layer was evaluated with a
      compartment model. These values ranged from 1.0 to 6.3 years/cm. The mean
      residence half-time averaged over all soil layers and all sites was 2.7 +/- 1.4
      years/cm and, thus, about twice the corresponding residence half-time of the
      Chernobyl-derived 137Cs as determined in the same soil layers (also in 1993). The
      dose rate of the external gamma-radiation due to 137Cs from global fallout in the
      soil determined from the depth distributions varied between 0.34 and 0.57 (mean:
      0.45 +/- 0.07) nGy/h per kBq/m2. The effect of soil water content on the dose
      rate was studied by considering four states of the soil, from water content zero
      to complete water saturation of the total pore volume. It was shown that the
      difference between the dose rates at the permanent wilting point and the field
      capacity, which both represent the most relevant water contents of soils, was
      only 10% of the dose rate at the permanent wilting point for all sites.

PMID- 9615341
TI  - Temporal variation of thoron decay product concentration in the atmosphere and
      comparison with radon decay product concentration.
AB  - Seasonal and long-term variation of the airborne 212Pb concentration,
      representative of the equilibrium equivalent concentration of thoron decay
      products (EECRn220), was investigated from 1989 through 1996 at a semi-natural
      location in southern Germany. Continuous measurement yielded a long-term average
      concentration of 0.082 Bq m-3, while daily mean concentrations varied from < or =
      0.01 to 0.34 Bq m-3. An average annual effective dose of 1.4 mSv due to outdoor
      thoron progeny concentration was estimated. This is about 2% of the dose due to
      the average short-lived radon progeny concentration (EECRn222) of 8.4 Bq m-3
      measured for this location in the same period. In most years the seasonal pattern
      of 212Pb activity concentration in the atmosphere is characterized by two maxima:
      the first in May and the second one in September. Low concentrations are observed
      from November through February of each year. This is in contrast to the behaviour
      of the short-lived 222Rn progeny which exhibit enhanced concentrations exactly
      during these months. The most probable reason for the different temporal
      behaviour of 212Pb is the extremely reduced flux of thoron gas from the ground
      during the winter months.

PMID- 9615342
TI  - Effects of gamma-irradiation on the electrokinetic properties of purple
      membranes.
AB  - The effect of gamma-irradiation (5, 10 and 15 Gy) on the kinetic surface charge
      of purple membranes (PM) was followed by means of particle microelectrophoresis.
      The changes in electrophoretic mobility (EPM) were examined at 2, 5 and 26 h,
      respectively, following irradiation of native PM, and at 2, 26, 50 h and 5 days
      following irradiation of delipidated PM. It was concluded that the high
      inhomogeneity of the suspension, even after sonication, largely affects the
      measured zeta-potential. The 15-Gy treatment significantly increased the net
      negative surface charge density at 5 and 26 h after irradiation of native PM.
      However, the opposite effect of approximately twofold reduction of EPM values was
      derived from simultaneous studies concerning their delipidated form. Low
      irradiation doses clearly induced an enhancement of negative surface charge
      density at 2 h post-exposure as well as the formation of unstable structures of
      delipidated PM. The changes in electrokinetic properties might reflect the
      specific aggregate formation in both native and delipidated PM. It was suggested
      that the effect observed of both types of PM was mainly a structural phenomenon
      possibly related to the modification of functionally active residues.

PMID- 9615343
TI  - Biological verification of heavy ion treatment planning.
AB  - Chinese hamster ovary (CHO) cells and thermoluminescent detectors (TLD-700) were
      used for physical and biological verification of heavy ion treatment planning.
      Experiments were performed in a cylindrical water phantom, in some cases with
      lung and bone equivalent material in front of the target volume. The results
      confirm the possibility of using thermoluminescent detectors for a quantitative
      verification of dose distributions. CHO cells can be used at least for
      qualitative dose verification.

PMID- 9615344
TI  - Infant leukemia in Belarus after the Chernobyl accident.
AB  - Petridou et al. [1] have reported an increase in infant leukemia in Greek
      children born between 1/7/86 and 31/12/87 and have linked this increase to in
      utero radiation exposure due to the Chernobyl accident. Subsequently, Michaelis
      et al. [2] have reported a similar trend for Germany but found that it was not
      correlated to the levels of contamination. For Belarus, which was much more
      severely affected, a similar but much weaker trend is found.

PMID- 9615345
TI  - Measurements of radioactivity in environmental samples from the southern Urals.
AB  - A region between Chelyabinsk and Ekaterinburg in the Southern Urals has been
      heavily contaminated due to operational and accidental releases from the first
      Soviet plutonium production facility Mayak. In 1992 and 1993, the German Federal
      Office for Radiation Protection organized a measuring campaign involving two
      Russian institutes to assist with the validation of former Soviet measurement
      data. The results of this measuring campaign are reported here. Environmental
      samples were collected from areas affected by significant radioactive releases
      into the Techa river, which started in 1948, and by fallout from the explosion of
      a fission product storage tank in 1957. Soil, sediment, water, milk and food
      samples were independently analysed for 90Sr, 137Cs and plutonium by the three
      institutes involved. This paper presents data on the present levels of
      environmental radioactivity. The highest contamination of areas accessible to the
      local population was found in the vicinity of the Techa river around Muslumovo.
      Activity concentration of floodplain samples reached up to 37,000 Bq.kg-1 137Cs,
      5,600 Bq.kg-1 90Sr and 9.9 Bq.kg-1 Pu. Milk and potatoes from private farms in
      Muslumovo showed low activity in the range from 0.7 Bq.kg-1 to 25 Bq.kg-1 90Sr.
      The results of the three independent measurement teams showed sufficient
      agreement. One Russian laboratory obtained plutonium activities that exceeded the
      results of the other laboratories by about 20%. Contrary to the International
      Chernobyl Project, there was no overestimation of 90Sr activities in the Russian
      analyses. Therefore, the validity of earlier data sets acquired with same
      methodology and quality control can be considered a valuable basis for further
      assessments and for dose reconstruction in epidemiological projects.

PMID- 9615346
TI  - Effects of melanin on high- and low- linear energy transfer (LET) radiation
      response of human epithelial cells.
AB  - The search for effective radioprotectors is of major concern in the medical,
      military, environmental, and space sciences. Conventional radioprotectors are
      generally effective only during a single irradiation and display their
      radioprotective properties only at high, toxic concentrations. In addition, they
      reduce somatic radiation effects but are poorly efficient in protecting from
      hereditary stochastic radiation effects. In this respect, the pigment melanin
      merits attention. Experiments referring to potential melanin effects on the
      ionising radiation response have been carried out with different biological
      systems, both in vivo and in vitro. In this paper, we present results on the
      response to high- and low-linear energy transfer (LET) radiation of a human
      mammary epithelial cell line, H184B5 F5-1 M/10, supplemented by melanin. The
      incorporation of auto-oxidative (L-dopa) melanin was linear for concentrations
      from 3 to 10 micrograms/ml in the growth medium. Concentrations of up to 250
      micrograms/ml did not significantly impair the cells proliferative ability. No
      significant protective effect of melanin on the survival of cultured cells after
      exposure to alpha-particles (130 keV/micron) or x-rays was observed.

PMID- 9615347
TI  - [The evolution of the lower jaw and the jaw joint, from reptiles to man].
AB  - The evolution of the mandible shows two characteristic features: transformation
      of the angular, articular and square bones in reptiles into the tympanic bone,
      malleus and incus of the middle ear respectively; and specific volume expansion
      of the tooth-bearing bone which in mammals comprises the entire mandible.
      Posture, locomotion and mastication are the basic evolutionary factors which
      simultaneously provoked 1) a displacement of the temporal regions, 2) a
      transformation of the face lowering and widening the lower jaw and 3) an
      elongation of the sutures uniting the different bones in the reptile jaw bone,
      progressively leading to their separation and transversal orientation. These
      transformations were accentuated in the biped. Thus in man the temporomandibular
      joint is in a very lateral and elevated position near the mastoids. The
      mandibular condyls are elongated transversally with a medial cantilever. The
      medial part of the meniscus is drawn medially by the lateral pterygoid while the
      lateral part is drawn laterally by the temporal and masseter fibers. The ramus is
      oriented vertically and lies close to the cervical spine. The dental arches are
      displaced posteriorly on the bone and have lost their anterior abutment. The
      strongest occlusal forces are displaced to the posterior part of the arches and
      are transmitted vertically to the intra-articular meniscus. All these phenomena
      are termed extreme adaptations and the temporomandibular joint would (apparently)
      suffer if the evolution continued. The architectural features of
      temporomandibular joint overload can be deducted by comparison with the "ideal"
      architectural conditions for the craniofacial equilibrium.

PMID- 9615348
TI  - [Orthodontic preparation for orthognathic surgery. Various specific points].
AB  - Orthodontic preparation before orthognatic surgery must straighten teeth
      alignment to enable correct adaptation of the upper and lower arches. It must
      also rectify dento-alveolar abnormalities partially responsible for the
      dysmorphosis and which can hinder smooth articulation of the bones. Thus before
      and after the operation, the orthodontist will have to prepare and monitor the
      surgical splints used in posterior deficiencies.

PMID- 9615349
TI  - [Sagittal osteotomy of the ascending ramus. Technic and value of transcutaneous
      basilar osteotomy].
AB  - Dalpont II sagittal osteotomy is the procedure of choice for prognathism. The
      surface for bone consolidation can be significantly increased by an anterior
      extension of the section, favored in cases with major skeletal imbalance.
      Neurosensorial or bone complications often compromise sagittal surgery. Section
      may be difficult if the basilary bone is particularly solid; simple section is
      not entirely satisfactory due to the risk and is not well adapted to Dalpont II
      osteotomy. We present a novel technique for transcutaneous basilar osteotomy
      using a modified transjugal retractor and a mini saw blade. This technique gives
      a Dalpont II sagittal osteotomy with a long reproducible and safe valve.

PMID- 9615350
TI  - [A large mucocele of unusual location].
AB  - We present the case of a patient who presented an unusually large mucoid cyst
      measuring 38 x 25 mm in an uncommon localization, the right maxillary. We examine
      the topographic and histological characteristics of mucoceles together with their
      treatment. The main differential diagnoses of liquid tumoral formations of the
      maxillary are also discussed.

PMID- 9615351
TI  - [Multiple lipoma of the tongue. Apropos of a case and review of the literature].
AB  - Lipomas are uncommonly located in the tongue and multiple forms are rare. We
      describe a case of multiple lipoma of the tongue in a female patient aged 60
      years who also presented subcutaneous cervical lipoma. The literature on multiple
      lipomas is discussed.

PMID- 9615352
TI  - [Florid cemento-osseous dysplasia: a poorly recognized entity. Apropos of 5
      cases].
AB  - We present five cases of florid osseous dysplasia observed in our department.
      There has been some confusion as to the terminology of this entity. We present
      here a review of the literature and outline the histological classification among
      odontogenic tumors as well as their epidemiology. The orthopantomogam is the
      mainstay radiological exploration, sometimes in association with a CT-scan. There
      are three main differential diagnoses: Paget's disease, Gardner's syndrome
      located in the maxillofacial area and diffuse sclerosing osteomyelitis.
      Asymtomatic forms motivate therapeutic abstenstion. When inflammatory, infectious
      or morphological complications appear, treatment relies on surgery in combination
      with long-term antibiotic regimens.

PMID- 9615353
TI  - [Recurrent parotitis in children and HIV infection. Apropos of 4 cases].
AB  - We report four cases of recurrent infectious parotiditis in children and recall
      the clinical radiographic and pathogenic features. Particular attention was paid
      to the possible relationship between sialadenitis and HIV infection in two cases.
      This would open a large etiological field when HIV contamination is suspected.
      Treatment if all four cases (spiramycine, diclofenac, soframycin washing,
      lipiodol instillation and local bucco-dental treatment) was successful leading to
      longer intervals between relapses.

PMID- 9615354
TI  - [Laugier-Hunziker syndrome. A clinical and anatomopathologic study. Presentation
      of 13 cases].
AB  - We report the clinico-pathologic characteristics of 13 cases of Laugier-Hunziker
      disease, consisting of the presence of oral melanotic macules associated or not
      to longitudinal nail pigmentation. The presence of regular acanthosis, basal
      pigmentation without increase in the number of melanocytes and the presence of
      melanophages in subepidermal connective tissue have been the most constant
      histopathological characteristics. The term "essential cutaneo-mucous
      hyperpigmentation" as synonym of Laugier-Hunziker disease is proposed.

PMID- 9615355
TI  - [Lichen and hepatitis C].
AB  - We report a case of lichen planus in a patient with hepatitis C infection and
      discuss the relationship between these two diseases.

PMID- 9615357
TI  - Evidence-based medicine.

PMID- 9615356
TI  - [Paranasal mucormycosis with involvement of the sphenoid sinus].
AB  - Mucormycosis with hemipansinusitis and left orbital involvement was observed in a
      66-year-old diabetic woman. Diagnosis was confirmed by mycology and pathology
      examinations. The patient was treated surgically with wide exeresis of necrotic
      tissue and medically with amphotericin B and insulin. Cure was obtained after
      three months of treatment at the cost of retraction of the left nostril due to
      infectious lysis and resection of the nasal infrastructure. The sinus involvement
      was exceptional compared with reports in the literature. Mucormycosis is an
      uncommon condition caused by opportunistic infection in immunodepressed subjects.
      The causal agent is a fungus belonging to the Rhizopus, Absidia or Mucor genera.
      Prognosis is poor with overall mortality reaching 50%.

PMID- 9615358
TI  - Spine: scientific citation index and its impact factor.

PMID- 9615359
TI  - Monocyte chemoattractant protein-1 in the intervertebral disc. A histologic
      experimental model.
AB  - STUDY DESIGN: Monocyte chemoattractant protein-1 was investigated in an
      experimental rat model using immunohistochemistry. OBJECTIVE: To ascertain the
      precise mechanism of macrophage recruitment in the early phase of disc
      resorption. SUMMARY OF BACKGROUND DATA: In previous studies, many investigators
      reported that disc herniation was resorbed by monocytic phagocytosis. However,
      how the recruitment of monocytes was triggered is still unknown. METHODS: The
      autologous intervertebral discs from tails of Wistar rats were subcutaneously
      implanted into the abdomen. These discs were obtained on days 2, 3, 7, and 14
      after implantation and were used for immunohistochemical study and for
      quantitative analysis of monocyte chemoattractant protein-1 by sandwich enzyme
      linked immunosorbent assay. RESULTS: Monocyte chemoattractant protein-1-positive
      granulocytes and macrophages were observed surrounding the intervertebral disc,
      and monocyte chemoattractant protein-1-positive disc chondrocytes were observed
      in the nucleus pulposus and the inner anulus fibrosus on day 3. By day 7,
      monocyte chemoattractant protein-1-positive and TRPM-3-positive macrophages
      appeared in the granulation tissue, and some of these cells invaded the nucleus
      pulposus and inner anulus fibrosus. The concentration of monocyte chemoattractant
      protein-1 was highest on day 3. CONCLUSION: Intervertebral disc chondrocytes have
      chemotactic properties and play an active role in the recruitment of monocytes
      involved in disc resorption.

PMID- 9615360
TI  - Quantitative anatomy of the occiput and the biomechanics of occipital screw
      fixation.
AB  - STUDY DESIGN: The surgically relevant osseous anatomy of the human anatomy was
      carefully studied and described. The stability of cortical and cancellous screws
      placed in anatomic sites commonly used for internal fixation of the occiput was
      tested. OBJECTIVES: To define the bony anatomy of the occiput in quantitative
      terms and to measure the ability of cortical and cancellous screws inserted at
      sites commonly used for internal fixation. SUMMARY OF BACKGROUND DATA: To the
      authors' knowledge, no previous studies described the gross anatomy of the
      occiput in specific relation to the internal venous structures in the cranium and
      to the biomechanical strength of screw fixation in different areas of the
      occiput. METHODS: Thirty-seven human occiputs were carefully measured using
      calipers. Thin sections from six such specimens were analyzed with specific
      attention to cortical thicknesses. Stability of screws placed in various
      locations in the occiput were tested in axial pullout. RESULTS: The thickness of
      the occiput varied from extremely thin to a 0.1-mm thickness in the region of the
      cerebellar fossa and increased to a maximum of 8.3 mm at the level of the
      superior nuchal line and at the transverse sulcus. Results of pullout testing
      showed that the cancellous screws were as strong as the cortical screws in this
      area. In areas of the occiput thicker than 7 mm, unicortical fixation was as
      strong as bicortical fixation. CONCLUSION: There is a wide variation in thickness
      of the bone of the occiput. The strength of screw fixation was proportional to
      the bone's thickness.

PMID- 9615361
TI  - Morphologic discrimination among healthy subjects and patients with progressive
      and nonprogressive adolescent idiopathic scoliosis.
AB  - STUDY DESIGN: A prospective and controlled comparative study. OBJECTIVES: To
      identify variables that would allow discrimination among patients with
      progressive adolescent idiopathic scoliosis, patients with nonprogressive
      adolescent idiopathic scoliosis, and control subjects. SUMMARY OF BACKGROUND
      DATA: In a previous study, the correlation was demonstrated between morphologic
      somatotypes and adolescent idiopathic scoliosis. METHODS: One hundred forty-six
      subjects were evaluated anthropometrically and were classified according to their
      morphologic somatotype. Of these subjects, 52 were adolescent girls with
      progressive idiopathic scoliosis, whereas 32 girls had nonprogressive idiopathic
      scoliosis. The control group was composed of 62 healthy adolescent girls.
      Somatotype values for ectomorphism, mesomorphism, and endomorphism were obtained
      according to a technique based on Sheldon's method, and 77 anthropometric
      measurements of segments of the thorax, head, and limbs were taken. RESULTS: The
      discriminant analysis realized on a subset of 18 variables allowed the correct
      identification of each subject's group in 84% of the cases. CONCLUSIONS: It is
      possible to differentiate healthy adolescent subjects, patients with
      nonprogressive adolescent idiopathic scoliosis, and patients with progressive
      idiopathic scoliosis by using anthropometric measurements and morphologic
      classification. These findings may be useful in the early detection of children
      at risk for progression of scoliosis and may allow earlier application of
      treatment methods without waiting for a significant increase in the curve.

PMID- 9615362
TI  - Classification of low back pain with the use of spectral electromyogram
      parameters.
AB  - STUDY DESIGN: An electromyogram procedure using spectral parameters to
      distinguish subjects with low back pain from those without. OBJECTIVES: To add to
      the growing database on this procedure, to assess the possible overfitting of
      data in the classification model, to determine whether a model based on a
      contraction level of 60% of maximum voluntary contraction can produce concordance
      rates similar to those in models based on 40% and 80% of maximum voluntary
      contraction, and to develop a classification model to distinguish subjects with
      low back pain from those without. SUMMARY OF BACKGROUND DATA: Other investigators
      have published a series of models in which spectral parameters measured during
      fatiguing contractions from the paraspinal muscles have been able to classify a
      subject into a low back pain or non-low back pain group with a more than 80%
      concordance rate. METHODS: Subjects with chronic low back pain (N = 21) and
      without (N = 18) performed a series of isometric, fatiguing back extensor
      contractions in which the median power frequency was measured bilaterally from
      T9, L3, and L5. A Student's t test was used to determine which parameters would
      be entered into the classification models. Discriminant analysis and logistic
      regression procedures were used to develop models to classify subjects and were
      compared for overfitting of data based on the number of input parameters. The
      logistic regression method used a holdout group (N = 6) for validation. RESULTS:
      The discriminant analysis selected all 10 input parameters and was believed to
      overfit the data. Logistic regression selected two parameters and had a
      concordance rate of 92.4%. Five of the six subjects in the holdout group were
      correctly classified. CONCLUSIONS: The use of spectral parameters to classify
      subjects with low back pain from those without appears to have merit. Compared
      with discriminant analysis, logistic regression provided an equally powerful
      method for classifying these two groups but did not overfit the data. Models
      based on 60% of maximum voluntary contraction demonstrated results comparable
      with those of previous research using 40% and 80% of maximum voluntary
      contraction.

PMID- 9615363
TI  - Manipulation does not alter the position of the sacroiliac joint. A roentgen
      stereophotogrammetric analysis.
AB  - STUDY DESIGN: A roentgen stereophotogrammetric analysis study of patients with
      sacroiliac joint dysfunction. OBJECTIVES: To investigate whether manipulation can
      influence the position between the ilium and the sacrum, and whether positional
      tests for the sacroiliac joint are valid. SUMMARY OF BACKGROUND DATA: Sacroiliac
      joint dysfunction is a subject of controversy. The validity of different
      sacroiliac joint tests is unknown. Long-standing therapeutic tradition is to
      manipulate supposed dysfunctions of the sacroiliac joint. Many manual therapists
      claim that their good clinical results are a consequence of a reduction of
      subluxation. METHODS: Ten patients with symptoms and sacroiliac joint tests
      results indicating unilateral sacroiliac joint dysfunction were recruited. Twelve
      sacroiliac joint tests were chosen. The results of most of these tests were
      required to be positive before manipulation and normalized after manipulation.
      Roentgen stereophotogrammetric analysis was performed with the patient in the
      standing position, before and after treatment. RESULTS: In none of the 10
      patients did manipulation alter the position of the sacrum in relation to the
      ilium, defined by roentgen stereophotogrammetric analysis. Positional test
      results changed from positive before manipulation to normal after. CONCLUSIONS:
      Manipulation of the sacroiliac joint normalized different types of clinical test
      results but was not accompanied by altered position of the sacroiliac joint,
      according to roentgen stereophotogrammetric analysis. Therefore, the positional
      test results were not valid. However, the current results neither disprove nor
      prove possible beneficial clinical effects achieved by manipulation of the
      sacroiliac joint. Because the supposed positive effects are not a result of a
      reduction of subluxation, further studies of the effects of manipulation should
      focus on the soft tissue response.

PMID- 9615364
TI  - Endoscopically assisted decompression for metastatic thoracic neoplasms.
AB  - STUDY DESIGN: The author describes a technique for complete vertebrectomy and
      anterior decompression followed by a formal anterior column reconstruction, using
      readily available endoscopic instruments. This procedure is indicated in patients
      with radioresistant metastasis of the thoracic spine, particularly those
      involving the upper thoracic segments where a thoracotomy is difficult and causes
      a high rate of morbidity. This is also a suitable technique for patients with
      pulmonary disease who cannot tolerate a standard thoracotomy. OBJECTIVES: To
      demonstrate the feasibility and potential benefits of endoscopically controlled
      decompression through an extrapleural, posterolateral approach. SUMMARY OF
      BACKGROUND DATA: Posterolateral decompression of the thoracic spine offers
      potential advantages in comparison with traditional anterior-posterior procedures
      combining thoracotomy and posterior instrumentation, including decreased
      operative time, decreased morbidity, and reduced hospital stay. Results of
      previous studies have not demonstrated the same benefit for posterolateral
      decompression as for anterior vertebrectomy and decompression. Drawbacks to the
      traditional posterolateral decompressions have included poor visualization of the
      spinal cord and anterior tumor, poor access to tumor on the side contralateral to
      the approach, and the need to manipulate the spinal cord to completely remove
      adjacent tumor and tumor adherent to the dura. METHODS: Surgical indications,
      rationale, and technique are provided, and initial clinical results are
      described. RESULTS: Transpedicular decompression using endoscopy is described in
      five patients. The mean operative time for the combined procedure was 7.25 hours,
      with a mean blood loss of 1800 mL. Neurologic recovery and maintenance were
      excellent. Inpatient days averaged 7.5, and intensive care days averaged 2. One
      patient died of disease 8 months after surgery, and four were living, with
      disease, 3-24 months after surgery. CONCLUSIONS: Endoscopically assisted
      decompression can reduce morbidity, hospital stay, and treatment costs while
      matching the efficacy of traditional combined procedures. Endoscopy provides a
      readily available and easily applied tool that dramatically improves the
      surgeon's vision, providing light, magnification, and a direct view of remote
      structures.

PMID- 9615365
TI  - Epidural spinal cavernous hemangioma.
AB  - STUDY DESIGN: Five cases of epidural spinal cavernous hemangioma submitted to
      magnetic resonance imaging and surgery were reviewed. OBJECTIVE: To correlate
      different magnetic resonance imaging appearances of epidural spinal cavernous
      hemangioma with histologic findings. SUMMARY OF BACKGROUND DATA: Cavernous
      hemangioma is an uncommon vascular malformation that may occur anywhere in the
      central nervous system. Purely epidural lesions are very rare. Accurate
      correlation between magnetic resonance imaging appearances and histologic
      findings have not been reported in the literature. METHODS: Five cases of
      epidural spinal cavernous hemangioma that had undergone magnetic resonance
      imaging evaluation followed by microsurgical removal, were retrospectively
      reviewed. Conventional spin-echo T1-, proton density- and T2-weighted magnetic
      resonance images were obtained in all cases, and gadolinium was used in all but
      one. Two cases have also been evaluated with computed tomography. RESULTS: In two
      cases, magnetic resonance imaging showed mixed low- and high-signal intensity
      components in all sequences and pathologic examination showed degenerative
      phenomena and hemosiderin pigments. In the remaining three cases, magnetic
      resonance imaging showed low- or intermediate-signal intensity on T1-weighted and
      high-signal intensity on proton density- and T2-weighted images. In those cases,
      pathologic examination showed an absence of degenerative phenomena and no signs
      of hemorrhage. All patients underwent surgery by laminectomy and microsurgical
      resection. In all, significant improvement was obtained. CONCLUSIONS: Epidural
      spinal cavernous hemangioma has a different magnetic resonance imaging appearance
      probably because of the presence or absence of the degenerative phenomena and
      hemosiderin pigments. As in cerebral locations, mixed signal intensity in all
      sequences on magnetic resonance images might be indicative of cavernous
      hemangioma. Presumptive preoperative diagnosis of the lesion may render the
      surgical approach less invasive.

PMID- 9615366
TI  - Use of ultrasound in spinal arthrodesis. A rabbit model.
AB  - STUDY DESIGN: The biomechanical and histologic characteristics of posterolateral
      spinal fusion in a rabbit model with and without the application of low-intensity
      ultrasound were analyzed. OBJECTIVES: To evaluate the use of ultrasound to
      improve the spinal fusion rate and biomechanical characteristics of the fusion
      mass in a rabbit model. SUMMARY OF BACKGROUND DATA: This is the first study in
      which the benefits of ultrasound in spinal fusion have been assessed.
      Posterolateral intertransverse process fusion in the rabbit has a pseudarthrosis
      rate similar to that recorded in humans (5-40%). METHODS: Fourteen New Zealand
      White rabbits were randomly assigned to each of two groups to undergo spinal
      fusion using autologous bone with ultrasound or autologous bone without
      ultrasound. A specially designed plastic constraint was used to focus the
      ultrasound over the rabbits' lumbar spine 20 minutes per day. Animals were killed
      at 6 weeks for biomechanical and histologic testing. RESULTS: The rate of
      pseudarthrosis, evaluated radiographically and manually in a blinded fashion,
      decreased at a statistically significant rate (from 35% to 7%) with ultrasound.
      Biomechanical analysis of the fusion mass showed that ultrasound resulted in
      statistically significant increases in stiffness (33%; P = 0.03), area under the
      load displacement curve (25%; P = 0.05), and load to failure of the fusion mass
      (24%; P = 0.04). Qualitative histologic assessment showed increased bone
      formation in those fusions exposed to ultrasound. CONCLUSIONS: Lumbar spinal
      fusion is a complex biologic process. The results of the current study
      demonstrate the reproducibility of a rabbit fusion model and the ability of
      ultrasound to induce a statistically significant increase in fusion rate,
      stiffness, area under the load displacement curve, and load to failure of the
      fusion mass. These results provide a basis for continued evaluation of biologic
      improvement of spinal arthrodesis with the use of ultrasound.

PMID- 9615367
TI  - Vascularization of the fusion mass in a posterolateral intertransverse process
      fusion.
AB  - STUDY DESIGN: A previously characterized rabbit model was used to study
      vascularization of the fusion mass in a posterolateral intertransverse process
      fusion. OBJECTIVES: To determine the interosseus origin of the new blood vessels
      in a posterolateral intertransverse process fusion mass and to test the
      hypothesis that bone incorporation and the extent of vascularization are closely
      related. SUMMARY OF BACKGROUND DATA: It has been reported that vascularization is
      essential for bone graft incorporation. There are, however, few reports dealing
      with vascularization of the spinal arthrodesis. METHODS: Thirty-one adult New
      Zealand White rabbits underwent bilateral intertransverse process fusion, using
      autogenous iliac crest bone graft. The rabbits were killed at 3 weeks (n = 6) and
      6 weeks (n = 25) after surgery, and colored silicone was injected to fix the
      vasculature. A semiautomated image analysis system was used to assess the
      percentage of the area of vascularization in the fusion mass and the transverse
      processes. RESULTS: The major interosseus blood supply for vascularization of the
      autogenous bone graft came from upper and lower transverse processes. There were
      three types of fusion mass observed at 6 weeks after surgery: solid type, solid
      type with cartilaginous cleft, and nonunion type. There was significantly less
      vascularization of the fusion mass and of the transverse processes in the
      nonunion type compared with that in the solid type and with that in the
      cartilaginous cleft type. CONCLUSIONS: There is a close correlation between bone
      incorporation and the extent of vascularization in a posterolateral
      intertransverse process fusion.

PMID- 9615368
TI  - Constrained testing conditions affect the axial rotation response of lumbar
      functional spinal units.
AB  - STUDY DESIGN: Human cadaveric spine specimens were tested in axial rotation using
      constrained and unconstrained methods. OBJECTIVES: To determine the degree to
      which constrained methods affect the response of the functional spinal unit in
      axial rotation at lumbar and lumbosacral levels. SUMMARY OF BACKGROUND DATA: A
      substantial controversy exists in the literature regarding the appropriateness of
      different testing methods. No study has been found in which the effect of
      constraint on axial rotation behavior was objectively examined. METHODS: Ten
      human cadaveric spine specimens (five L3-L4, five L5-S1) were tested in axial
      rotation, using both constrained and unconstrained methods. In the unconstrained
      test, pure moments were applied to the upper vertebra, and its complete three
      dimensional motion was measured using an optoelectronic camera system. In the
      constrained test, the specimens were loaded in a fixed-axis servohydraulic test
      machine individually around five rotational axis positions within the vertebral
      body, and the rotational motion was measured. RESULTS: The rotational angles in
      the constrained tests were not different among the five rotational axis
      positions. However, the maximum rotation from the five axis positions was
      approximately 40% greater than the minimum rotation, a significant difference.
      The axial rotational motion of the unconstrained tests was always less than the
      maximum rotation measured in the constrained test. However, the total rotational
      angle using the helical axis of motion was not significantly different from the
      constrained angles. CONCLUSIONS: The large differences between maximum and
      minimum rotation angles demonstrate that the behavior of the functional spinal
      unit in axial rotation is sensitive to the axis's position but the location of
      the axis is not repeatable. This supports the use of unconstrained methods in
      spinal testing.

PMID- 9615369
TI  - Tuberculous lesions of the lumbosacral region. A 15-year follow-up of patients
      treated by ambulant chemotherapy.
AB  - STUDY DESIGN: A 15-year clinical follow-up of tuberculous lesions of the
      lumbosacral region. OBJECTIVES: To verify the hypothesis that the lumbar lordosis
      and the specific biomechanics of the lumbosacral region influence and alter the
      healing pattern and progress of the disease when compared with their effects in
      other regions of the spine. SUMMARY OF BACKGROUND DATA: An estimated 2 million or
      more patients have active spinal tuberculosis, and the global incidence of the
      disease is increasing. The involvement of the lower lumbar region and the
      lumbosacral junction is relatively rare, with few reports in English literature.
      METHODS: Of a total of 304 patients forming a part of a controlled clinical trial
      comparing two forms of therapy in spinal tuberculosis, 53 patients had
      involvement of L3 and below. The following data were studied in these patients:
      age at start of treatment, number of vertebra involved, vertebral body loss,
      progress of the angle of kyphosis, and anterior and posterior growth of the
      involved segment during a period of 15 years. Student's t test for independent
      samples was used for statistical analysis. RESULTS: The fourth lumbar vertebra
      was the most common vertebral segment involved, and the lumbosacral junction was
      affected in 12 patients. The average pretreatment kyphosis was 6.4 degrees and
      increased to 10.2 degrees at the end of 15 years. The average kyphotio angle per
      vertebral body loss was 4.9 degrees, far less than in the dorsolumbar region in
      which kyphotic angles of 27-30 degrees have been reported. Children younger than
      10 years old differed in clinical appearance and progress compared with those
      older than 17 years. They not only showed more extensive involvement but also had
      more deformity with the same vertebral loss. Twelve patients less than 10 years
      old had an average involvement of 3.1 vertebral bodies and an average vertebral
      loss of 2.2 bodies. In comparison, the average number of vertebrae involved was
      1.9 (P < 0.01) and the vertebral body loss was only 0.87 (P < 0.01) in patients
      older than 17 years. Also, the average kyphosis was 6.4 degrees compared with
      only 4.2 degrees (P < 0.01) in adults. In patients older than 17 years, there was
      no change after 2 years, by which time the collapse was complete. Four of 12
      patients less than 10 years old, showed progressive kyphosis caused by continued
      growth of posterior parts of the body (i.e., sequestrated hemivertebrae).
      CONCLUSIONS: In tuberculosis of the lumbosacral region, the development of
      kyphosis is minimal in patients older than 17 years, when growth has already
      stopped, and deformity is expressed more as foreshortening of the trunk. Children
      younger than 10 years old have more severe involvement with increased tendency
      toward greater kyphosis. They are also prone to progressive deformity through the
      years when the anterior growth plates are destroyed. Surgery is indicated in this
      group to prevent greater deformity.

PMID- 9615370
TI  - A 10-year follow-up of the outcome of lumbar microdiscectomy.
AB  - STUDY DESIGN: A retrospective analysis of the outcome of lumbar microdiscectomy,
      with independent assessment of outcome. OBJECTIVES: To explore whether the
      initial positive outcome after microdiscectomy is maintained at long-term follow
      up. SUMMARY OF BACKGROUND DATA: Previous reports on long-term outcome after
      lumbar disc surgery give conflicting messages about whether an initially positive
      surgical outcome is maintained throughout a 10-year period. This is partly due to
      differing methods and the failure to include initial outcome, thereby permitting
      assessment of possible deterioration in the quality of outcome. METHODS: This
      study presents the initial and long-term outcome after lumbar microdiscectomy,
      with an independent assessment of outcome. Eighty-eight consecutive patients
      undergoing lumbar microdiscectomy were identified. Assessment at 10 years after
      surgery was obtained in 79 (90%) of the cases. The initial outcome was assessed
      retrospectively by an independent observer at 6 months after surgery using the
      Macnab classification. The final outcome Macnab classification was completed by
      postal questionnaire by the patients themselves, who also completed a modified
      Roland-Morris disability questionnaire. RESULTS: A successful outcome at 6 months
      was achieved in 91% of the cases. At 10-year follow-up, this result declined
      slightly to an 83% success rate. However, there was no statistically significant
      difference between these outcome results. The long-term Macnab classification
      results correlated well with disability, as measured by the Roland-Morris score.
      Patient satisfaction with the results of microdiscectomy 10 years later was high.
      CONCLUSIONS: Lumbar microdiscectomy achieves a high level of initial success, and
      this positive outcome is maintained at a 10-year follow-up.

PMID- 9615371
TI  - The Graf ligamentoplasty procedure. Comparison with posterolateral fusion in the
      management of low back pain.
AB  - STUDY DESIGN: A retrospective case-control comparison between the Soft Tissue
      Stablization System according to Graf and instrumented posterolateral fusion in a
      consecutive series of patients operated on by a single surgeon. OBJECTIVES: To
      compare clinical and radiologic outcomes at 1 and 2 years. SUMMARY OF BACKGROUND
      DATA: Although series have been reported showing encouraging results with the use
      of the Graf ligamentoplasty for low back pain no comparative data are available
      on outcome when compared with those in more conventional treatments. METHODS:
      Eighty-three consecutive patients operated on for low back pain in a single
      surgeon's practice (TMH) were recalled for clinical and radiologic review.
      Patients underwent either soft tissue stabilization or posterolateral fusion with
      pedicle screw instrumentation. Each patient chose between the procedures after
      advice that the Soft Tissue Stabilization System, although experimental, was a
      reversible procedure. Independent observers conducted the review at 1 and 2
      years. The Low Back Outcome Score was used as an objective measure of outcome. In
      addition to this, patients underwent computed tomographic assessment of pedicle
      screw placement. RESULTS: There was no statistically significant difference
      between groups in age, sex, body weight, symptom duration, previous surgery,
      dependency on workers' compensation, preoperative diagnosis, smoking habits, and
      the number of motion segments instrumented. There was a significantly better
      outcome, when measured by the Low Back Outcome Score in the group of patients
      managed by posterolateral fusion at 1 year (P = 0.02), although at 2 years the
      difference was less (P < 0.34). Patients with facet joint-related pain did no
      better after Soft Tissue Stabilization than did patients of other diagnostic
      groups. Compensable cases did better at 1 year after fusion (P < 0.003), although
      again the difference was less marked at 2 years (P = 0.09). There was a trend
      toward a higher revision rate in the Soft Tissue Stabilization System group (P =
      0.11) at 1 year with a statistically significant (P = 0.01) difference apparent
      at 2 years. Revision after Soft Tissue Stabilization was associated with a poorer
      outcome, similar to that seen in revision after fusion. Pedicle screw
      misplacement rates were no different between the two groups and increased in
      frequency at the more cranial vertebral levels. CONCLUSIONS: Outcome after Soft
      Tissue Stabilization was associated with a worse outcome at 1 year and a
      significantly higher revision rate at 2 years. Revision was associated with a
      poor outcome similar to that seen in revision after fusion.

PMID- 9615372
TI  - Translaminar screw fixation of the lumbar and lumbosacral spine. A 5-year follow
      up.
AB  - STUDY DESIGN: In a retrospective study, the long-term results of translaminar
      facet screw fixation of the lumbar and lumbosacral spine are reviewed.
      OBJECTIVES: To evaluate the clinical results, fusion rates and complications of
      this posterior fusion technique in various conditions of the lumbar spine.
      SUMMARY OF BACKGROUND DATA: Posterior fusion of the lumbar and lumbosacral spine
      is one of the possible methods to relieve pain and eliminate instability in
      degenerative conditions. Data in the literature support the use of internal
      fixation to optimize the rate of fusion. METHODS: Posterior lumbar and
      lumbosacral fixation with translaminar screws and fusion in 173 patients with
      degenerative changes with or without compressive syndromes including failed back
      syndromes, monosegmental hypermobilities, and posttraumatic conditions were
      investigated. Fixation and fusion with translaminar screws was performed in 57%
      monosegmentally, in 40% across two segments and in 2% over three segments.
      Decompressive surgery was performed in addition in 52% and nucleotomy in 30% of
      the cases. Clinical and radiologic assessment with flexion/extension x-rays was
      performed in 145 (83%) patients by two independent orthopedic surgeons. After an
      average follow-up of 68 months (range, 52-83). RESULTS: Ninety-four percent of
      the patients showed solid bony fusion in the radiologic follow-up. Loosening of
      the screws was noted in 3%, and two screws were broken without apparent motion on
      the functional x-rays. Pain scores decreased from 7.6 before surgery to 2.9 after
      surgery on a 10-point pain scale. The results were further analyzed according to
      Stauffer and Coventry with 99 good results, 70 satisfactory results, and 4 bad
      results. CONCLUSIONS: Translaminar screw fixation offers an immediate
      postoperative stability of the lumbar and lumbosacral spine and enhances fusion.
      In the present series no neurologic complications were noted. It represents a
      useful and inexpensive technique for short segment fusion of the nontraumatic
      lumbar and lumbosacral spine.

PMID- 9615373
TI  - [The Law Medical Scientific Research with Humans and Father Cats' morals].

PMID- 9615374
TI  - [Quality of life: CVA patients take stock].
AB  - The approach of the concept 'quality of life' in stroke research is often multi
      dimensional; and the dimensions to be studied, are chosen by the researcher. To
      determine the most important dimensions or aspects of quality of life--from the
      point of view of stroke patients--we interviewed 75 patients one year, and 83
      patients two years after their stroke. These interviews were part of a longterm
      follow-up of a cohort of 221 stroke patients. Seventy-five percent of both the
      one- and two-year survivors experienced a deterioration of quality of life.
      Autonomy appeared to be the most important aspect of quality of life, being
      spontaneously mentioned by 55% of 75 patients. Compared with the stroke patients,
      an age- and sex-matched group of 61 controls rated their quality of life more
      highly. For them, autonomy appeared to be less important, being spontaneously
      mentioned by 25% of 61 controls. Furthermore, stroke patients attached more
      importance to social contacts and activities and general health than controls. We
      suggest to lend more weight in research and medical care, to patients' priorities
      in quality of life.

PMID- 9615375
TI  - [The right to complain under the BOPZ Act (Formal Admissions to Psychiatric
      Hospitals): experiences in psychogeriatrics].
AB  - The Act on Formal Admissions to Psychiatric Hospitals (BOPZ) enables
      psychogeriatric patients to complain. According to a BOPZ evaluation study
      concerning the right to complain, which was held in 1995 and 1996, the current
      procedure to complain appears to be inadequate for psychogeriatric patients. The
      Act on the right to complain, which came into force recently, didn't improve this
      procedural inadequacy. We suggest to improve the right to complain both at the
      level of government as at the institutional level. The right to complain could
      thus contribute substantially to the legal position of the psychogeriatric
      patient and the quality of health care. The introduction of a client informant is
      recommended.

PMID- 9615376
TI  - [What carries more weight, safety or freedom? Contact persons on physical
      restraint of psychogeriatric nursing home patients].
AB  - All representatives of psychogeriatric patients of two Dutch nursing homes (in
      Nijmegen and Amsterdam) were asked for their opinion about the use of (physical)
      restraints. Questions referred to characteristics of the respondents and their
      relatives in the nursing home, information provided by the nursing home, and
      decision-making. Furthermore respondents' opinion was studied by means of
      statements on six patient cases for whom respondents could choose the application
      of any type of restraint or no restraint. 77% (321) of all 416 representatives
      who were sent a questionnaire responded. The majority (75%) was well informed on
      the existence of several types of physical restraints, one third of the
      respondents, however, answered that information provided by the nursing home in
      this respect was lacking. 55% of the respondents answered that there was only a
      need for information on physical restraint when a problem concerning their family
      member actually occurs. Almost 90% of the respondents wanted to play an active
      role in decision-making or at least be informed before or shortly after
      application of a restraint. From the answers on the statements a majority of the
      respondents may be concluded to choose for safety above freedom for their
      relatives. Belts tied to a chair or bed, but also chairs with tables across, were
      judged to be the most restraining and influential on the mood of the relatives.
      The answers regarding the six patient cases show that a majority of the
      respondents choose any type of restraint. In most cases they choose for less
      restraining devices and for devices with less or no influence on the mood. About
      one-third of the representatives of the Amsterdam nursing home answered that
      their relatives ever had had any application of a restraint, while in the
      Nijmegen nursing home this prevalence was twice as high. In many aspects
      Amsterdam respondents were more critical about the application of restraints.
      This could probably be explained by the difference in policy of restraint
      application between the two nursing homes.

PMID- 9615377
TI  - [The treatment of locally advanced (T3) prostatic carcinoma using radical
      prostatectomy or radiotherapy. A review].
AB  - In the Netherlands 16% of all newly diagnosed prostatic carcinomas are already
      locally advanced (TNM-system: T3), which means that the tumor spreads beyond the
      prostatic capsule, or grows into the seminal vesicles. The pre-operative clinical
      staging is not very reliable when local tumor extension is concerned: the
      sensitivity for detecting extracapsular extension is 67% for digital rectal
      examination and 58% for transrectal ultrasonography of the prostate. In 50% of
      clinically locally confined tumors spread outside the prostate is found; and in
      18% of the T3 tumors the tumor is confined to the prostate. In most clinics
      patients with locally advanced tumors are not considered to be candidates for
      radical prostatectomy, because the margins are small, due to anatomical factors.
      Progression and survival reported in the research literature for patients treated
      by radical prostatectomy for T3 prostate cancer are, however, at least equal to
      those treated with radiotherapy, which is considered the standard treatment for
      this stage. The average 10-year percentages for progression and survival of T3
      prostate cancer patients treated by radical prostatectomy (or radiotherapy) are:
      clinical progression: 40% (radiotherapy: 61%); local recurrence 18% (35%);
      biochemical progression: 60% (93%); survival: 63% (39%); and prostate cancer
      specific survival: 78% (44%). These success-rates can not be compared directly,
      because of differences in physical condition and staging between the groups,
      which favor the radical prostatectomy group. There is, however, a subgroup of
      patients with undifferentiated carcinoma which shows high progression rates
      following radical prostatectomy; these patients need adjuvant hormonal treatment,
      or should be given a different therapy. The role of adjuvant radiotherapy
      following radical prostatectomy is still a matter of debate, as is the
      administration of neoadjuvant hormonal therapy. For the moment these therapies
      should only be given in clinical trials.

PMID- 9615378
TI  - [Current challenges for scientific research in geriatrics].
AB  - Conducting medical research on geriatric patients differs essentially from
      conducting research on other types of patients. Recruitment and selection of
      research subjects are difficult, primarily because many geriatric patients will
      be judged as incapable to consent to participate in scientific research.
      Moreover, the frailty of geriatric patients requires research instruments that do
      not trouble subjects too much and research should be aimed at identifying causes
      of change in functional performances and quality of life. Large randomized
      controlled clinical trials are very hard to perform in geriatrics, although this
      research design is considered the most valuable. Therefore, individual treatment
      decisions generally cannot be evidence based because of a lack of controlled
      geriatric research or because of uncertainties in individualizing available
      evidence. In this paper three research designs will be discussed that may be
      helpful in bridging the gap between evidence and patient care: qualitative
      research methods, longitudinal research to quantify change in time and
      interindividual differences in chronic disease, and single patient research aimed
      at evidencing pharmacotherapeutic decisions in individual elderly patients. These
      research designs are not new, but they are undervalued and sparsely used.
      Qualitative research can clarify differences in patients' treatment preferences
      and motivation and their consequences. Cohort-studies of geriatric patients can
      show the effects of complex and long lasting medical histories on current
      treatment options. Single patient research can replace non-systematic trial and
      error by randomized controlled trials per patient.

PMID- 9615379
TI  - Endogenous lipid pneumonia- and alveolar proteinosis-type changes in the vicinity
      of non-small cell lung cancer: histiopathologic, immunohistochemical, and
      ultrastructural evaluation.
AB  - Endogenous lipid pneumonia (ELP) and pulmonary alveolar proteinosis (AP) are the
      most common pathological conditions of lung tissue in which there is an increased
      accumulation of surfactant elements in pulmonary alveoli. This paper evaluates
      the morphology, morphogenesis, and pathogenesis of ELP- and AP-type changes in
      the immediate vicinity of non-small cell lung cancer (NSCLC). The analyses used
      lung tissue obtained from the vicinity of 56 NSCLC. ELP- or/and AP-type changes
      in histopathological studies were found in lung tissue surrounding 35 NSCLC.
      Ultrastructural analyses by transmission electronmicroscopy identified 15 cases
      with advanced ELP and confirmed the possibility of coexistence of ELP- and AP
      type changes in the vicinity of NSCLC and the evolution of ELP into AP. Most
      cases analyzed showed morphological features characteristic of both AP and ELP,
      the intensity and degree of these changes being considerably differentiated. Type
      II pneumocytes, macrophages, and neutrophilic granulocytes play a significant
      part in the morphogenesis of ELP and AP.

PMID- 9615380
TI  - Ultrastructural and histochemical study of the motor end plates of the intrinsic
      laryngeal muscles in amyotrophic lateral sclerosis.
AB  - Motor end plates of the intrinsic laryngeal muscles in amyotrophic lateral
      sclerosis (ALS) were examined light and electron microscopically. Light
      microscopically, typical neurogenic changes such as small angulated fibers and
      grouped atrophy were found in the intrinsic laryngeal muscles.
      Acetylcholinesterase (AchE) activities of the neuromuscular junctions (NMJ) of
      many fibers in ALS were decreased as compared with those of the controls. Some
      end-plate areas on each fiber detected by AchE histochemistry were larger than
      those of the controls. Ultrastructurally, muscle fibers in ALS specimens showed
      several changes; increased number of lipofuscin granules and/or nuclei, numerous
      mitochondria, and disappearance of the myofilaments. The NMJ also showed various
      degrees of structural changes. Some NMJ appeared almost normal. Others showed the
      absence of nerve terminals and Schwann cells covering the former junctional
      sites. Their primary synaptic clefts were flattened, and the secondary synaptic
      clefts were relatively well preserved. On occasion, several small nerve terminals
      were seen on the severely distorted postsynaptic folds, suggesting regenerative
      findings. In severely degenerated muscle fibers, the NMJ could not be found.

PMID- 9615381
TI  - Fibrous long-spacing collagen in bacillary angiomatosis.
AB  - Fibrous long-spacing (FLS) collagen is a distinct ultrastructural form of
      collagen present in normal tissue, various tumors, and tissues degraded by
      bacterial collagenases in vivo and in vitro. An association between FLS collagen
      and bacillary angiomatosis has not been previously described. Six cases of
      bacillary angiomatosis, including one autopsy case with disseminated disease,
      were examined ultrastructurally. In addition, Kaposi sarcoma (3), pyogenic
      granuloma (3), capillary hemangioma (3), and cavernous hemangioma (2) were
      examined for comparison. A vascular proliferation in a lymph node from a patient
      with AIDS (1) and a case of pulmonary capillary hemangiomatosis (1), also in an
      AIDS patient, were studied. Abundant FLS collagen was identified in 4 of 6 cases
      of bacillary angiomatosis, in close association with the organisms. FLS collagen
      was not seen beyond the immediate vicinity of the organisms. The FLS collagen in
      bacillary angiomatosis was seen in skin biopsies and in lung and skeletal muscle
      in the autopsy case; in the latter case, as well as in the two AIDS-associated,
      nonbacillary angiomatosis, non-Kaposi sarcoma vascular proliferations, there was
      a striking distribution of FLS collagen around small blood vessels. Occasional
      FLS collagen was observed in all three pyogenic granuloma. When present in
      pyogenic granuloma, FLS collagen was intermixed with subendothelial collagen.
      Abundant FLS collagen was identified in close association with the organisms of
      bacillary angiomatosis in four cases; this morphologic alteration was seen in
      skin as well as lung and skeletal muscle. An association between FLS collagen and
      endothelial cells in normal tissue (Descemet's membrane) and in certain vascular
      proliferations appears to exist.

PMID- 9615382
TI  - Granuloma faciale: an ultrastructural study.
AB  - Granuloma faciale is an uncommon process that can easily be confused with other
      skin diseases. To avoid incorrect treatment, correct diagnosis is of primary
      importance. A diagnosis of granuloma faciale can be made by a microscopic study
      of the dense granulomatous infiltrate in the reticular dermis with abundant
      polynuclear eosinophils and by an ultrastructural study of the eosinophils, which
      show characteristic alterations in their cytoplasmatic granules. The absence of
      Langerhans granules differentiates granuloma faciale from histiocytosis X.

PMID- 9615383
TI  - Value of electron microscopy and immunohistochemistry in the diagnosis of soft
      tissue tumors.
AB  - Light microscopy alone is often insufficient to type a soft tissue tumor. In this
      study 142 consecutive soft tissue tumors (benign or malignant), for which both
      electron microscopy (EM) and immunohistochemistry (IHC) had been performed, were
      reviewed to assess the contribution of these two modalities to making the final
      diagnosis. A tentative diagnosis (58 cases) or differential diagnosis (84 cases)
      was made following light microscopical examination. Ultrastructural and
      immunohistochemical features were then reviewed. Overall, EM more often
      contributed to diagnosing the tumor type than IHC (80 vs. 65%), with a
      statistically significant difference (p = .001). This was most apparent in high
      grade sarcomas (grade III); the contribution of the two modalities was similar in
      benign and low-grade malignant tumors. IHC more often than EM (33% vs 22%) did
      not provide information to aid in typing of the tumor. However in 47% of the
      cases in which one of the two modalities was noncontributory, the other technique
      was helpful in reaching a diagnosis. These findings suggest that both IHC and EM
      are necessary to properly evaluate soft tissue tumors.

PMID- 9615384
TI  - Pancreatic endocrine tumor with signet ring cell features: a case report with
      novel ultrastructural observations.
AB  - The case of a malignant pancreatic endocrine neoplasm with an unusual signet ring
      cell appearance is reported. The tumor was resected from a 30-year-old man with a
      4.0-cm tumor in the body of the pancreas diagnosed by computerized tomographic
      (CT) scan. The resected tumor had a unique morphology characterized by numerous
      mucin-negative, signet ring cells, which were argyrophilic and immunoreactive for
      cytokeratin (CAM 5.2), chromogranin, synaptophysin, neuron specific enolase, and
      gastrin. Dense-core neurosecretory-type granules and numerous cytoplasmic
      lamellar inclusions were identified by electron microscopy. These inclusion
      bodies consisted of multilayered concentric osmiophilic lamellae (myelin
      figures), which most likely represent an abnormal accumulation of degenerating
      organelles. Two years later, the patient developed an abdominal recurrence of the
      tumor, confirming its malignant behavior. This case expands the spectrum of
      pancreatic endocrine tumors to include an aggressive signet ring cell tumor with
      a novel ultrastructural basis.

PMID- 9615385
TI  - Malignant plasmacytoid myoepithelioma of the palate: histological observations
      compared to benign predominant plasmacytoid myoepithelial cells in pleomorphic
      adenoma of the palate.
AB  - Predominant benign plasmacytoid myoepithelial cells in pleomorphic adenoma and
      malignant plasmacytoid myoepithelioma cells were investigated morphologically.
      The cells of both tumors were plasmacytoid in appearance and sheet-like.
      Immunohistochemically, they were positive for keratin, vimentin, and S-100
      protein, and negative for alpha-smooth muscle actin. In the malignant cells,
      large nuclei with irregular nuclear membranes and distinct nucleoi and occasional
      intranuclear inclusions and nuclear grooves were seen. Ultrastructural findings
      showed that the benign cells were richer in intermediate filaments and had fewer
      mitochondria. The intranuclear inclusions and nuclear grooves of the malignant
      cells were caused by invagination of the irregular nuclear membranes. Taken in
      their entirety, the above light microscopical nuclear findings may be useful as
      an adjunct for distinguishing malignant from benign plasmacytoid neoplastic
      myoepithelial cells of the salivary gland.

PMID- 9615386
TI  - Astroglial tangles in the hippocampus of two patients with Down syndrome and
      Alzheimer neuropathology.

PMID- 9615387
TI  - Mixed solid papillary and mucinous carcinoma of the breast.

PMID- 9615388
TI  - Localization of antigens associated with adherens junctions, desmosomes, and
      hemidesmosomes during murine molar morphogenesis.
AB  - Epitheliomesenchymal interactions are known to play a crucial role during
      odontogenesis. Since epithelial cell-cell and cell-matrix interactions may also
      be involved in enamel organ histomorphogenesis, we investigated the localization
      of proteins associated with junctional complexes in mouse and rat first lower
      molars by indirect immunofluorescence. Adherens junctions were detected using
      antibodies directed against E-cadherin, beta-catenin, and plakoglobin (gamma
      catenin). Desmosomes were localized with antibodies against desmoglein, and
      hemidesmosomes using antibodies against BP-230 and HD-1 proteins. When the inner
      dental epithelium differentiates, a decrease of E-cadherin, plakoglobin, and BP
      230 is seen. An asymmetric distribution of plakoglobin, desmoglein, and BP-230
      between the lateral and medial side of the tooth exists; desmoglein, which was
      first restricted to the gubernaculum dentis, progressively accumulated in the
      stellate reticulum, the stratum intermedium, and the basal pole of ameloblasts.
      The specific temporospatial distributions patterns of these antigens suggests a
      direct involvement of adherens junctions, desmosomes, and hemidesmosomes in the
      development of the murine first lower molar.

PMID- 9615389
TI  - Characterization of different cell populations isolated from rat testis
      peritubular cells.
AB  - Peritubular cells, a mixed population of myoid and non-myoid cells obtained by
      enzymatic treatments of rat seminiferous tubules, are currently utilized as a
      myoid cell population. We have morphologically and biochemically compared
      peritubular cells and purified myoid cells isolated from prepubertal rats. The
      two cell populations appear morphologically similar when cultured in the presence
      of serum: both appear to be composed of elongated cells when observed by phase
      contrast microscopy. However, the two populations differ in the percentage of
      alkaline phosphatase positive cell since only a minority of the cells present in
      the peritubular cell population are positive for alkaline phosphatase expression.
      Secretory activity of myoid cells is higher when compared to the peritubular cell
      secretion. To the contrary, fibronectin is highly synthesized and secreted by the
      peritubular cells, suggesting that the non-myoid cells synthesize fibronectin at
      a high level. Myoid cells have also been cultured in a chemically defined medium
      without any serum addition. In this experimental condition the cells show a
      polygonal shape, which remains constant during culture time. Secretory activity
      and fibronectin synthesis and secretion of the cells cultured without serum are
      lower when compared to the values obtained in the presence of serum at the
      beginning of the culture. Moreover, the distribution of the cell-associated
      fibronectin is modified by the culture conditions: spotted on cells cultured in
      the absence of serum and fibrillar on cells cultured with serum. We therefore
      conclude that peritubular cells and myoid cells are significantly different cell
      populations and that serum addition to the culture medium dramatically influences
      the morphology and the metabolic activities of the myoid cells.

PMID- 9615390
TI  - Transitional stages in the development of the rabbit renal collecting duct.
AB  - The collecting duct (CD) epithelium of the mammalian kidney is an extraordinary
      structure with respect to its functional changes during development and its
      heterogeneous composition when matured. All of the different nephron epithelia of
      the mammalian kidney consist of one single cell type. In contrast, the
      differentiated CD is composed of at least three distinct cell types [principal,
      alpha intercalated-, and beta intercalated cells] that are responsible for the
      multiple physiological functions of this kidney compartment. During development
      the function of the CD changes: initially, the CD ampulla serves as an embryonic
      inducer, while the matured epithelium plays a key role in maintaining the
      homeostasis of body fluids. At present the process of CD maturation is not well
      understood. Neither the time course of development nor the morphogenic factors
      leading to the heterogeneously composed epithelium are known. In the present
      study the differentiation of the CD epithelium was investigated using newly
      developed monoclonal antibodies and well-characterized antisera. The
      morphological changes induced during differentiation were monitored by
      immunohistochemistry and scanning electron microscopy. The experiments were
      performed on neonatal and adult rabbit kidneys. Results obtained by light
      microscopical techniques and scanning electron microscopy revealed that the
      ampullary tip can be distinguished from the ampullary neck, as well as from the
      maturing CD. A number of proteins that were not detectable in the ampulla were
      detected in the neonatal CD and were found at even higher concentrations in the
      adult CD (PCD8, chloride/bicarbonate exchanger). Other proteins (PCD9) were
      downregulated during differentiation. For the first time the transient character
      of the differentiation stage of the neonatal CD could be demonstrated
      unequivocally. Furthermore, considerable heterogeneity in protein expression
      patterns (PCD6 and PCD9) was demonstrated within the beta IC cell population of
      the mature CD.

PMID- 9615391
TI  - Divergent effects of bryostatin 1 and phorbol myristate acetate on cell cycle
      arrest and maturation in human myelomonocytic leukemia cells (U937).
AB  - Bryostatin 1 and the phorbol ester, phorbol myristate acetate (PMA), both bind to
      and activate protein kinase C (PKC) but exhibit divergent biological actions.
      Bryostatin 1 exerts variable effects on leukemic cell differentiation, and has
      been reported by some investigators to inhibit the proliferation of the monocytic
      leukemic cell line U937. In this study, we have compared the efficacy of
      bryostatin 1 and PMA with respect to U937 cell maturation, with a major emphasis
      on differential actions on the cell cycle arrest machinery. At equimolar
      concentrations (10 nM), PMA, in contrast to bryostatin 1, induced cellular
      differentiation of U937 cells, reflected by growth inhibition, increased plastic
      adhesion, and expression of the monocytic differentiation marker, CD11b.
      Consistent with these results, bryostatin 1 was less effective in inducing G0/G1
      arrest and inhibiting cyclin-dependent kinase 2 (CDK2) activity. Bryostatin 1,
      unlike PMA, failed to induce expression of the cyclin-dependent kinase inhibitor
      (CDKI), p21CIP1/WAF1, and blocked the ability of PMA to induce this protein.
      Bryostatin 1 exposure resulted in increased expression of the CDKI p27KIP1 in
      these cells, although the kinetics differed from PMA. In addition, bryostatin 1
      was less effective than PMA in dephosphorylating pRb, modifying E2F complexes,
      and downregulating c-Myc. Co-administration of bryostatin 1 with PMA antagonized
      the latter's differentiation-inducing capacity and anti-proliferative effects,
      actions that were accompanied by a reduction in PMA-mediated p21CIP1/WAF1
      induction, CDK2 inhibition, pRb dephosphorylation, and c-Myc downregulation.
      Antagonistic effects of bryostatin 1 on PMA-related cell cycle events were
      mimicked by the specific PKC inhibitor GF109203X. Together, these studies
      indicate that bryostatin 1 is a considerably weaker stimulus than PMA for U937
      cell differentiation, and raise the possibility that this deficiency arises from
      its failure to induce p21CIP1/WAF1 and trigger cell cycle arrest.

PMID- 9615392
TI  - Distribution of the CD15 epitope in the mammalian developing lung is opposite in
      mouse compared with human.
AB  - The distribution of the expression of the CD15 epitope was characterized by
      immunohistochemistry in the developing mouse and human lung on embryonic days
      E9.5-E19 and gestational weeks GW7-GW25, respectively. In the earliest stages in
      the mouse, the tracheal epithelial cells expressed CD15 on their apical and
      lateral cell membranes and, in the more proximal regions, also showed a faint
      cytoplasmatic CD15 expression. Only very few epithelial cells in the bronchial
      bud regions expressed CD15 on their apical surfaces. In later stages (E12-E17),
      cells in the proximal parts of the bronchi and bronchioli expressed CD15 on their
      apical, but also on their lateral membranes, and increasing numbers of cells
      expressed CD15 cytoplasmatically. Cells in the distal, presumably proliferating,
      areas of the bud regions were CD15 negative. This distribution pattern of CD15
      was consistent until the latest embryonic stages. These results are completely
      opposite to those found in human developing lung where up to GW20 bronchial and
      bronchiolar bud regions were CD15 positive, while in the proximal parts of the
      airways the vast majority of cells were CD15 negative. After GW20, CD15
      immunoreactivity in the bud regions vanished and was completely absent on GW25.
      This difference between human and mouse adds further evidence to profound species
      differences in the expression of CD15 in various organs, e.g., in the cerebellum
      or the retina, and should be taken into account when considering functional roles
      of CD15 and also when relating results from a (transgenic) mouse model to the
      respective human organ system.

PMID- 9615393
TI  - Theoretical analysis of the effect of the transbilayer movement of phospholipid
      molecules on the dynamic behavior of a microtube pulled out of an aspirated
      vesicle.
AB  - Observations over extended times of a lipid microtube (tether) formed from a
      lecithin vesicle have shown that under constant external loads the tether
      exhibits a continuous slow growth. It is considered that this growth is a
      consequence of the net transbilayer movement of phospholipid molecules in a
      direction which relieves the membrane strain resulting from the elastic
      deformation of the vesicle. The elastic deformation mode responsible for this
      effect is identified as the relative expansion of the two membrane layers
      reflecting the non-local contribution to membrane bending. An equation for the
      consequent rate of transbilayer movement of phospholipid molecules is derived.
      The dynamic behavior of the system is modeled by including frictional
      contributions due to interlayer slip and Stokes drag on the glass bead used to
      form the tether. The general numerical solution reveals a complex dependence of
      the tether growth rate on the system parameters and a continuous increase in the
      rate of tether growth at long times. Closed form expressions approximating the
      system behavior are derived and the conditions under which they can be applied
      are specified. Modeling the mechanically-driven lipid transport as a simple,
      stochastic, thermal process, allows the rate of lipid translocation to be related
      to the equilibrium transbilayer exchange rate of phospholipid molecules.
      Consideration of experimental results shows that the time constant for
      mechanically-driven translocation is shorter than the time for diffusion-driven
      translocation by approximately two orders of magnitude, indicating that lipid
      translocation is not a simple diffusive process.

PMID- 9615394
TI  - Interaction between dihydropyridines and phospholipid bilayers: a molecular
      dynamics simulation.
AB  - Interaction of the calcium-channel antagonist dihydropyridines (DHPs), lacidipine
      and nifedipine, with a phospholipid bilayer was studied using 600 ps molecular
      dynamic simulations. We have constructed a double layer membrane model composed
      of 42 dimirystoyl-phosphatidylcholine molecules. The DHP molecules locate at
      about 7 A from the centre of the membrane, inducing an asymmetry in the bilayer.
      While lacidipine did not induce significant local perturbations as judged by the
      gauche-trans isomerisation rate, nifedipine significantly decreased this rate,
      probably by producing a local rigidity of the membrane in the vicinity of the
      DHP.

PMID- 9615395
TI  - A comparative study of the action of melittin on sphingomyelin and
      phosphatidylcholine bilayers.
AB  - To investigate whether lipid solubilization is of relevance in describing the
      interaction between melittin and biological membranes, we studied melittin
      induced polymorphism using model membranes composed of the biological lipid
      sphingomyelin (bovine brain). The behavior of the system was monitored by solid
      state 31P-NMR and turbidity measurements and compared to the peptides well
      characterized action on the synthetic lipid dipalmitoylphosphatidylcholine. It
      was found that melittin-induced macroscopic changes of sphingomyelin membranes
      are qualitatively the same as in the case of dipalmitoyl-phosphatidylcholine
      bilayers. The sphingomyelin/melittin system is thus proposed to show a reversible
      vesicle-to-disc transition (fluid-to-gel phase) through an intermediate fusion or
      aggregation event centered at the main transition temperature, Tm, as reported in
      the case of saturated phosphatidylcholine. In the case of spontaneous disc
      formation at 37 degrees C, the lipid-to-peptide molar ratio in the discoidal
      objects was determined to be approximately 20 for dipalmitoylphosphatidylcholine
      and about 12 in the case of natural sphingomyelin. Melittin partition
      coefficients between membranes and the aqueous medium at 37 degrees C were found
      to be 6.1 +/- 0.8 mM-1 and 3.7 +/- 0.4 mM-1 for sphingomyelin and
      dipalmitoylphosphatidylcholine, respectively. For very high peptide quantities
      (lipid-to-peptide molar ratio, Ri < or = 5) mixed micelles are formed over the
      entire temperature range (20 degrees to 60 degrees C) for both kinds of lipids.

PMID- 9615396
TI  - NMR measurements of Ca2+ and H+ transport mediated by A23187 and reconstituted
      plasma membrane Ca(2+)-ATPase.
AB  - NMR-based assays for measuring the fluxes of Ca2+, H+, and ATP in liposomal
      systems are presented. The 19F NMR Ca(2+)-chelating molecule 5,5-difluoro-1,2
      bis(o-amino-phenoxy)ethane-N,N,N',N'-tetraacetic acid (5FBAPTA) was trapped
      inside large unilamellar vesicles and used to monitor passive and A23187-mediated
      Ca2+ transport into them. The data were analyzed using progress curves of the
      transport reaction. They demonstrated the general applicability of 5FBAPTA as a
      19F NMR probe of active Ca2+ transport. 31P NMR time-courses were used to monitor
      simultaneously the ATP hydrolysing activity of the reconstituted human
      erythrocyte Ca(2+)-ATPase and the concomitant acidification of the reaction
      medium in a suspension of small unilamellar vesicles. Using an estimate of the
      extraliposomal buffering capacity, the H+/ATP coupling stoichiometry, in the
      presence of A23187, was estimated from the NMR-derived data at steady state; it
      amounted to 1.4 +/- 0.3. This result is discussed with respect to the issue of
      molecular 'slip' in the context of a non-equilibrium thermodynamics model of the
      pump (accompanying paper in this issue). Importantly, NMR, in contrast to optical
      detection methods, can potentially register all fluxes and (electro)chemical
      gradients involved in the Ca(2+)-ATPase-mediated H+/Ca2+ counterport, in a single
      experiment.

PMID- 9615397
TI  - A non-equilibrium thermodynamics model of reconstituted Ca(2+)-ATPase.
AB  - A non-equilibrium thermodynamics (NET) model describing the action of completely
      coupled or 'slipping' reconstituted Ca(2+)-ATPase is presented. Variation of the
      coupling stoichiometries with the magnitude of the electrochemical gradients, as
      the ATPase hydrolyzes ATP, is an indication of molecular slip. However, the Ca2+
      and H+ membrane-leak conductances may also be a function of their respective
      gradients. Such non-ohmic leak typically yields 'flow-force' relationships that
      are similar to those that are obtained when the pump slips; hence, caution needs
      to be exercised when interpreting data of Ca(2+)-ATPase-mediated fluxes that
      display a non-linear dependence on the electrochemical proton (delta mu H) and/or
      calcium gradients (delta mu Ca). To address this issue, three experimentally
      verifiable relationships differentiating between membrane leak and enzymic slip
      were derived. First, by measuring delta mu H as a function of the rate of ATP
      hydrolysis by the enzyme. Second, by measuring the overall 'efficiency' of the
      pump as a function of delta mu H. Third, by measuring the proton ejection rate by
      the pump as a function of its ATP hydrolysis rate.

PMID- 9615398
TI  - Lysozyme crystal growth, as observed by small angle X-ray scattering, proceeds
      without crystallization intermediates.
AB  - A combination of small angle X-ray scattering and gel techniques was used to
      follow the kinetics of protein crystal growth as a function of time. Hen egg
      white lysozyme, at different protein concentrations, was used as a model system.
      A new sample holder was designed, in which supersaturation is induced in the
      presence of salt by decreasing the temperature. It had been shown previously that
      a decrease in temperature and/or an increase in crystallizing agent induces an
      increase in the attractive interactions present in the lysozyme solutions, the
      lysozyme remaining monomeric. In the present paper we show that similar behaviour
      is observed in NaCl when agarose gels are used. During crystal growth, special
      attention was paid to determine whether oligomers were formed as the protein in
      solution was incorporated in the newly formed crystals. From these first series
      of experiments, we did not find any indication of oligomer formation between
      monomer in solution and crystal. The results obtained are in agreement with the
      hypothesis that lysozyme crystals in NaCl grow by addition of monomeric
      particles.

PMID- 9615399
TI  - Ion chromatography on anion exchangers modified with mucopolysaccharides.
AB  - Anion exchangers modified with mucopolysaccharides, such as chondroitin sulfates
      and heparin, were used for the stationary phase in ion chromatography. Unusual
      retention behavior of anions was observed for the modified stationary phases. A
      50-microM concentration of tartaric acid could separate inorganic anions in a
      reasonable time. The retention of analytes could be changed by changing the
      eluent composition.

PMID- 9615400
TI  - Analysis of oxyhalides in water by ion chromatography-ionspray mass spectrometry.
AB  - A sensitive method for analyzing chlorite, chlorate, bromate and iodate in water
      by ion chromatography (IC) coupled with ionspray tandem mass spectrometry (IS-MS
      MS) has been developed. Prior to analysis, samples were subjected to off-line
      sample clean-up with Ba, Ag and H-form resins to remove sulfate, chloride and
      hydrogencarbonate, respectively. Oxyhalides in the purified samples were
      concentrated and separated on a short, high-performance anion-exchange column. An
      eluent consisting of ammonium nitrate in methanol-water (9:1, v/v) was found to
      be suitable for separating the analytes, while providing enhanced detector
      sensitivity. The coupling of IC with IS-MS-MS allows for the identification of
      the four oxyhalides mentioned above in a single run with very high specificity
      and sensitivity.

PMID- 9615401
TI  - Determination of iodide in ground water and soil by ion chromatography.
AB  - Comprehensive elemental analysis of samples from the Bear Creek Valley near the
      Oak Ridge Y-12 Plant, and its floodplain have been performed in order to allow an
      unclassified assessment of possible elemental contamination within this area. A
      rapid ion Chromatographic method, with isocratic separation and micromembrane
      suppression is discussed within this paper for the analysis of iodide in soils,
      and floodplain ground waters. This developmental method will be used for future
      routine iodide analysis.

PMID- 9615402
TI  - New, sensitive and selective method for determining sub-microgram/l levels of
      bromate in drinking water.
AB  - Health effects studies suggest that bromate should be regulated at 0.5
      microgram/l or less in drinking water. Accordingly, an analytical method is
      needed to quantify this contaminant with great sensitivity and selectivity. Past
      efforts to do this have focused on pre-concentration ion chromatographic (IC)
      separation followed by suppressed conductivity detection. Interfering chloride
      was removed by passing samples over a silver resin which increased sample
      analysis time to almost 1 h. In this paper, a new method which uses IC separation
      with no pre-treatment followed by a post-column reaction to produce tribromide
      (Br3-) from bromate, is applied to the analysis of a variety of aqueous samples.
      The tribromide ion is detected by UV absorbance at 267 nm. This method is very
      sensitive for bromate with a limit of quantitation of 0.2 microgram/l and is also
      very selective. Common anions typically separated by IC exhibit no interference,
      even at the levels normally found in drinking water.

PMID- 9615403
TI  - Ion chromatographic determination of nitrate and nitrite in meat products.
AB  - Nitrate and nitrite are usually added to processed meat products to provide
      protection against microorganisms that cause food poisoning. Nitrite may react
      with secondary amines to form nitrosoamines, a class of carcinogens. Nitrate,
      although it is more stable than nitrite, can act as a reservoir for nitrite.
      Thus, both nitrate and nitrite need to be monitored to ensure the quality and
      safety of meat products. In this paper, an accurate and sensitive method is
      described by which nitrate and nitrite are extracted from food samples, then
      analyzed by ion chromatography (IC). Commercial samples of ham and salami were
      analyzed by IC with UV absorbance detection. UV absorbance was specific for
      nitrate and nitrite, eliminating interference from other ions present at much
      higher concentrations. Recoveries of nitrate and nitrite were greater than 90%.
      The method was linear (r2 > 0.999) over the working range, and detection limits
      for nitrate and nitrite were 50 micrograms/l and 30 micrograms/l, respectively.

PMID- 9615404
TI  - Ion-exchange chromatography of mono- and divalent cations in natural waters on a
      weak-acid anion-exclusion column.
AB  - Ion-exchange chromatography with indirect conductimetric detection for the
      simultaneous determination of mono- and divalent cations is investigated using an
      anion-exclusion chromatographic column packed with polymethacrylate-based weakly
      acidic cation-exchange resin in the H+ form (Tosoh TSKgel OA-PAK-A, 300 mm x 7.8
      mm I.D.). An eluent comprising a strong acid, a weak organic acid, methanol and
      water is used. Using 0.75 mM sulfuric acid, 2 mM tartaric acid, 7.5% (v/v)
      methanol in water as eluent, the monovalent cations (Na+, NH4+, and K+) and
      divalent cations (Mg2+ and Ca2+) were separated simultaneously by a cation
      exchange mechanism in about 25 min. The application of this method to the
      analysis of several natural waters including rain, river, lake, underground and
      forest soil waters for estimating acid rain effects on the natural and urban
      environments is presented.

PMID- 9615405
TI  - Improved application of ion chromatographic determination of carboxylic acids in
      ozonated drinking water.
AB  - A direct ion chromatographic method of measuring carboxylic acids was modified
      and expanded to include measurement of eight components at parts-per-billion
      levels. These components, listed by eluting order, were acetate, propionate,
      formate, pyruvate, glyoxalate, dichloroacetate, oxalate and ketomalonate. The
      calculated method detection limits were 2-6 micrograms/l. Preliminary data were
      obtained by using California state project water from the filter influent of the
      Oxidation Demonstration Plant of the Metropolitan Water District of Southern
      California. Oxalate was measured at levels above 200 micrograms/l, formate above
      100 micrograms/l, acetate above 50 micrograms/l, pyruvate and glyoxalate at
      approximately 30 micrograms/l and propionate and ketomalonate at trace levels
      near the detection limits. This method utilizes a new preservative, benzalkonium
      chloride, as a substitute for the environmentally unsafe mercuric chloride that
      had previously been used. Preservation studies indicate that all eight compounds
      are stable for a testing period of 30 days when benzalkonium chloride is
      maintained at or above 30 mg/l in the water sample.

PMID- 9615406
TI  - Application of ion chromatography to the semiconductor industry. I. Measurement
      of acidic airborne contaminants in cleanrooms.
AB  - The purpose of this study is to establish an analytical method for the
      simultaneous measurement of various acidic airborne contaminants in class 1
      cleanrooms of a semiconductor fabrication facility (Fab). Acidic contaminants in
      air samples were adsorbed on silica gel tubes, extracted with carbonate
      hydrogencarbonate solutions, and analyzed by ion chromatography. The recovery of
      HF was 100% and that of HCl was 91 approximately 100%. The method shows high
      resolution and sensitivity, and is capable for air analysis in the class 1
      cleanroom. Different locations inside the cleanroom show deviations in the
      contaminant levels, indicating that the air quality is not the same throughout
      the cleanroom. The wet chemical station shows higher levels of contaminant
      concentrations than the other two areas. Each location also shows day-to-day
      variation.

PMID- 9615407
TI  - Detection of counterfeit and relabeled infant formulas by high-pH anion-exchange
      chromatography-pulsed amperometric detection for the determination of sugar
      profiles.
AB  - High pH anion-exchange separation with pulsed amperometric detection (HPAE-PAD)
      is used to characterize various milk-based, soy-based, and protein hydrolysate
      infant formulas based on carbohydrate profiles. Counterfeit and relabeled
      formulas are compared to authentics. Figures of merit are shown for glucose,
      fructose, lactose, sucrose, and maltose.

PMID- 9615408
TI  - Analysis of water from the Space Shuttle and Mir Space Station by ion
      chromatography and capillary electrophoresis.
AB  - Drinking water and condensate samples collected from the US Space Shuttle and the
      Russian Mir Space Station are analyzed routinely at the NASA-Johnson Space Center
      as part of an ongoing effort to verify water quality and monitor the environment
      of the spacecraft. Water quality monitoring is particularly important for the Mir
      water supply because approximately half of the water consumed is recovered from
      humidity condensate. Drinking water on Shuttle is derived from the fuel cells.
      Because there is little equipment on board the spacecraft for monitoring the
      water quality, samples collected by the crew are transported to Earth on Shuttle
      or Soyuz vehicles, and analyzed exhaustively. As part of the test battery, anions
      and cations are measured by ion chromatography, and carboxylates and amines by
      capillary electrophoresis. Analytical data from Shuttle water samples collected
      before and after several missions, and Mir condensate and potable recovered water
      samples representing several recent missions are presented and discussed. Results
      show that Shuttle water is of distilled quality, and Mir recovered water contains
      various levels of minerals imparted during the recovery processes as designed.
      Organic ions are rarely detected in potable water samples, but were present in
      humidity condensate samples.

PMID- 9615409
TI  - Magnetic relaxation dispersion of 7Li. II. Complex formation with nitroxides in
      the aqueous phase.
AB  - Measurements of 7Li nuclear spin-lattice relaxation times are made at applied
      magnetic field strengths from 0.25 mT to 7.05 T, in order to determine directly
      the form of the frequency-dependent spectral densities that modulate relaxation.
      This magnetic resonance dispersion (MRD) technique provides detailed information
      regarding molecular dynamics down to the picosecond time scale. 7Li MRD
      measurements made on aqueous lithium ion in the presence of small concentrations
      of nitroxide free radicals give direct evidence supporting the formation of a
      coordination complex. The dipole-dipole electron-nuclear coupling is modulated by
      both translational and rotational diffusive motions, and both of these
      contributions are resolved. However, scalar coupling arising from the presence of
      paramagnetic electron spin density at the nucleus dominates the nuclear
      relaxation. Changes in the pH and free radical moiety are compared with dynamical
      variables, geometric constraints, and formation constants obtained from a model
      of nuclear relaxation. The calculated bimolecular formation constants are on the
      order of 2 x 10(-3) M-1, and the relative accuracy of this parameter is tested.

PMID- 9615410
TI  - 3D accordion spectroscopy for measuring 15N and 13CO relaxation rates in poorly
      resolved NMR spectra.
AB  - An experimental approach for the measurement of nuclear magnetic spin relaxation
      rate constants that combines triple-resonance techniques and accordion
      spectroscopy is described. Pulse sequences are discussed for the measurement of
      backbone 15N and 13CO R1 relaxation rate constants. The three-dimensional HNCO
      triple-resonance technique is employed to gain improved spectral resolution over
      conventional two-dimensional methods by frequency labeling both the 15N and 13CO
      spins. Accordion spectroscopy is used to reduce the dimensionality of the
      relaxation experiment. The "negative-time accordion" approach (A. M. Mandel and
      A. G. Palmer (1994), J. Magn. Reson. A 110, 62-72) is used for extracting rate
      constants from the t1 interferograms. The experiments are demonstrated using a
      13C/15N isotopically enriched sample of the third fibronectin type III domain of
      human tenascin.

PMID- 9615411
TI  - Interresidue quiet NOEs for DNA structural studies.
AB  - The potential utility of long-range NOEs in DNA has not been exploited since the
      observed signals have contributions both from the direct magnetization route and
      from multiple diffusion pathways. The Quiet NOE approach can be used to select
      for the direct magnetization transfer pathway by suppressing spin diffusion. A
      single-band Quiet NOE, which allows detection of the direct NOEs between protons
      in a selected chemical shift window, has been demonstrated on two duplex DNAs,
      and the NOEs observed can contain important structural information.

PMID- 9615412
TI  - Uniform-penalty inversion of multiexponential decay data.
AB  - NMR relaxation data and those from many other physical measurements are sums of
      exponentially decaying components, combined with some unavoidable measurement
      noise. When decay data are inverted in order to give quasi-continuous
      distributions of relaxation times, some smoothing of the distributions is
      normally implemented to avoid excess variation. When the same distribution has a
      sharp peak and a much broader peak or a "tail," as for many porous media
      saturated with liquids, an inversion program using a fixed smoothing coefficient
      may broaden the sharp peak and/or break the wide peak or tail into several
      separate peaks, even if the coefficient is adaptively chosen in accord with the
      noise level of the data. We deal with this problem by using variable smoothing,
      determined by iterative feedback in such a way that the smoothing penalty is
      roughly constant. This uniform-penalty (UP) smoothing can give sharp lines, not
      broadened more than is consistent with the noise, and in the same distribution it
      can show a tail decades long without breaking it up into several peaks. The noise
      level must be known approximately, but it can be determined more than adequately
      by a preliminary inversion. The same iterative procedure is used to implement
      constraints such as non-negative (NN) or monotonic-from-peak (MT). The
      significance of an additional resolved peak may be tested by finding the cost of
      using MT to force a unimodal solution. A bimodal constraint can be applied. Decay
      data representing sharp lines in contact with broad features can require
      substantial computing time and some controls to stabilize the iterative sequence.
      However, UP can be made to function smoothly for a very wide variety of decay
      curves, which can be processed without adjustment of parameters, including the
      dimensionless smoothing parameters. Extensive testing has been done with
      artificial data. Examples are shown for artificial data, biological tissues,
      ceramic technology, and sandstones. Expressions are given relating noise level to
      line width and for significance of increase or decrease in error of fit.

PMID- 9615413
TI  - Bloch-Siegert shift compensated and cyclic irradiation sidebands eliminated,
      double-adiabatic homonuclear decoupling for 13C- and 15N-double-labeled proteins.
AB  - A Gaussian-shaped, offset-independent adiabatic decoupling is adopted to decouple
      13CO from 13C alpha or vice versa for 13C- and 15N-double-labeled proteins,
      together with a compensating decoupling applied on the opposite side of the 13C
      alpha resonance frequency. In a quite broad range, the double-adiabatic
      decoupling eliminates efficiently the cyclic sidebands caused by direct
      irradiation of the adiabatic decoupling and reduces significantly the Bloch
      Siegert shift. The remaining Bloch-Siegert shift, which is almost a linear
      function of offset, can be removed by a dilated evolution time. The decoupling
      sequence is also quite insensitive to the RF field intensity or inhomogeneity due
      to the reduced transverse components of RF field at 13C alpha, leading to an
      efficient decoupling even under unfavorable conditions.

PMID- 9615414
TI  - Pulsed gradient NMR probes for solid state studies.
AB  - Recently introduced studies of the spatial characteristics of spin dynamics in
      dipolarly coupled solids rely upon NMR probes with strong magnetic field
      gradients to create spatial magnetization gratings with periods of from 1 micron
      to 1 nm. The measurements are carried out as scattering experiments where the
      spatial displacement of spin coherence is recorded as a phase shift or
      attenuation of the magnetization grating. Recently we have employed these
      techniques to make a direct measurement of the spin diffusion rate in single
      crystal CaF2. Here we discuss designs for strong pulsed gradient NMR probes.
      Three gradient coil sets were designed and constructed, with coil constants of
      0.32, 0.67, and 4.15 T/m/A. When driven by a pulsed current source that provides
      up to 300 A, pulsed gradients of 100, 200, and 600 T/m, respectively, were
      generated. These designs are fully described, along with practical issues of coil
      heating and probe stability.

PMID- 9615415
TI  - Simple correction method for k-space trajectory deviations in MRI.
AB  - A method is presented to correct for the imperfections of spatial encoding
      gradients in MRI. The approach is simple and fast, can be performed with standard
      scanner hardware, and does not require separate measurements with reference
      phantoms. The new method, using the MR signal to accurately measure the k-space
      trajectory of the imaging sequence, allows for correction of gradient hardware
      imperfections and eddy-current effects. Initial measurements are presented which
      demonstrate the efficacy of the method to correct images acquired with spiral and
      EPI scan techniques.

PMID- 9615417
TI  - Investigation of the trans effect in the fragmentation of dinuclear platinum
      complexes by electrospray ionization surface-induced dissociation tandem mass
      spectrometry.
AB  - Cis and trans isomers of two dinuclear platinum complexes, [cis-?Pt(NH3)2Cl?2 mu
      (NH2(CH2)nNH2)](NO3)2 (1,1/c,c) and [trans-?Pt(NH3)2Cl?2 mu-(NH2(CH2)nNH2)](NO3)2
      (1,1/t,t), where the diamine was 1,4-butanediamine (n = 4) or 1,6-hexanediamine
      (n = 6), were studied using electrospray ionization surface-induced dissociation
      (ESI/SID) tandem mass spectrometry (MS/MS). The same fragment ions were observed
      for both the cis and trans isomers of each complex (n = 4 or 6), but the relative
      intensities were dependent on the isomer studied. The ESI/SID data and energy
      resolved mass spectra show that the position of the chloride plays a significant
      role in the fragmentation of these ions. Two major fragmentation pathways were
      detected for the complexes. The cleavage of the Pt-N bond trans to chloride was
      the most favorable pathway for both isomers of the complexes following the ion
      surface collision. The differences in the ESI/SID spectra between the cis and
      trans isomers can be explained by the trans effect, namely that the Pt-N bond
      trans to chloride is the most labile bond.

PMID- 9615416
TI  - Improved cross peak detection in two-dimensional proton NMR spectra using
      excitation sculpting.
AB  - In two-dimensional homonuclear experiments, reliable detection of very small
      cross peaks is sometimes hampered by t1-noise from larger diagonal peaks which
      have the same F2 frequency. This t1-noise can be selectively removed by recording
      partial 2D spectra using the double pulsed field gradient spin echo (DPFGSE).
      Resonances not selected by the DPFGSE do not contribute any t1-noise to the
      resulting spectrum. The absence of t1-noise from the diagonal peaks render the
      small cross peaks at the same F2 frequency observable. The success of this
      technique is shown by partial 2D NOESY and TOCSY spectra.

PMID- 9615418
TI  - Gluconeogenesis in isolated rat hepatocytes evaluated by gas chromatography/mass
      spectrometry using deuterated water.
AB  - Tritiated water and radioactive tracers have been used to monitor glucose
      production by primary cultures of hepatocytes. More recently, 3H2O has been
      replaced for by 2H2O in 'in vivo' studies addressed at the evaluation of the
      relative contribution of gluconeogenesis to total glucose production. In this
      work, the possibility of using 2H2O to determine the ratio between the glucogenic
      flux and the overall flux through glucose 6-phosphate in isolated liver cells in
      vitro was evaluated. For this purpose, hepatocytes from either fasted or fed rats
      were incubated with a medium containing 6, 12 and 25% of 2H2O in the presence of
      either 2 or 20 mM pyruvate. Isotopomer analysis of six different mass clusters
      (m/z 328, 314, 242, 212, 187 and 145) was carried out by gas chromatography/mass
      spectrometry (GC/MS) of glucose aldonitrile pentaacetate. For each cluster, ions
      at m/z +1, +2, +3 and +4 were monitored. From the combination of different
      clusters the enrichment at C-6 and C-2 of glucose was computed and the C-6/C-2
      ratio was considered to represent the contribution of gluconeogenesis to total
      glucose production, as suggested previously. Based on the results obtained,
      conditions selected to be optimum for the use of the method in studies on the
      modulation of gluconeogenesis were as follows: incubation of hepatocytes with 20
      mM pyruvate in 12% 2H2O followed GC/electron ionization MS analysis of the
      clusters of ions at m/z 328, 314 and 187 of the glucose derivative to calculate
      enrichment at the C-2 and C-6 positions of glucose.

PMID- 9615420
TI  - Identifying causes of disagreement between self-reports and spouse ratings of
      personality.
AB  - Self-reports and spouse ratings of personality traits typically show less-than
      perfect agreement, but powerful moderators of agreement have not yet been
      identified. In Study 1, 47 married couples completed the Revised NEO Personality
      Inventory to describe themselves and their spouses. Extent of agreement was not
      consistently moderated by response sets; the age, intelligence, or education of
      the respondent; or the length or quality of the relationship. In Study 2 these
      couples were interviewed about reasons for substantial disagreements, and an
      audiotape was content-analyzed. Sixteen reasons were reliably coded, including
      idiosyncratic understanding of items, reference to different time frames or
      roles, and unavailability of covert experience to the spouse. Faking good,
      assumed similarity, and other variables prominent in the psychometric literature
      were relatively unimportant. Findings (1) suggest that attempts to improve the
      validity of self-reports and ratings may need to be refocused and (2) underscore
      the desirability of routinely obtaining multiple sources of information on
      personality.

PMID- 9615419
TI  - Poly(ethylene glycol) limits of detection using internal matrix-assisted laser
      desorption/ionization Fourier transform mass spectrometry.
AB  - Detection limits of poly(ethylene glycol) were examined in the mass range 2000
      6000 Da. Using an aerospray sample deposition technique, highly uniform sample
      surfaces were produced. This method allows signal averaging of spectra from up to
      400 shots on the same sample spot. It is found that, as the material available
      for desorption is decreased, the overall average sample consumption per shot is
      decreased. Experimentally determined detection limits of 40 and 280 fmol (based
      on the average molecular masses of 2000 and 6000) were found for PEG 2000 and PEG
      6000, respectively. The sample spectra show oligomer distributions in agreement
      with their higher concentration counterparts. However, at the lowest signal-to
      noise levels, oligomers at the extremes of the distribution are no longer
      detected, making the polymer distribution appear to be narrower in mass range.

PMID- 9615421
TI  - Threat to gender representation: identity and identification.
AB  - To investigate the effect of a threat to gender identity on the use of defense
      mechanisms, college students were given false feedback regarding their sex-role
      identity. Male and female students who were given gender-contrary feedback showed
      a marked increase in the use of the defense of identification, as compared to
      students who were given gender-consistent feedback. Further, both affect change
      and the use of identification was a function of the degree of discrepancy between
      feedback condition and conscious gender identity.

PMID- 9615422
TI  - Terror management and meaning: evidence that the opportunity to defend the
      worldview in response to mortality salience increases the meaningfulness of life
      in the mildly depressed.
AB  - Previous terror management research has demonstrated that mildly depressed
      participants show a greater increase in worldview defense in response to
      reminders of their mortality than do nondepressed participants. Because the
      cultural worldview is posited to provide a meaningful conception of life, we
      hypothesized that mildly depressed participants who defend their worldview in
      response to mortality salience (MS) would increase their perception that the
      world is meaningful. A preliminary study first examined the Kunzendorf No Meaning
      Scale as a measure to assess perceptions of meaning. In the primary study, mildly
      depressed and nondepressed participants contemplated their own mortality or a
      neutral topic, evaluated two targets in a manner that either allowed them to
      defend their worldview or that did not, and then completed the Kunzendorf No
      Meaning Scale. As predicted, mildly depressed participants who had the
      opportunity to defend their worldview in response to mortality salience reported
      greater meaning in life than did mildly depressed participants who did not have
      the opportunity to defend their worldview, or mildly depressed participants not
      exposed to mortality salience. Implications for understanding and treating
      depression are briefly discussed.

PMID- 9615424
TI  - Time series analysis in historiometry: a comment on Simonton.
AB  - Time series analysis (TSA) is one of a number of new methods of data analysis
      appropriate for longitudinal data. Simonton (1998) applied TSA to an analysis of
      the causal relationship between two types of stress and both the physical and
      mental health of George III. This innovative application demonstrates both the
      strengths and weaknesses of time series analysis. Time series is applicable to a
      unique class of problems, can use information about temporal ordering to make
      statements about causation, and focuses on patterns of change over time, all
      strengths of the Simonton study. Time series analysis also suffers from a number
      of weaknesses, including problems with generalization from a single study,
      difficulty in obtaining appropriate measures, and problems with accurately
      identifying the correct model to represent the data. While careful attempts are
      made to minimize these problems, each is present in the Simonton study, although
      sometimes in a subtle manner. Changes in how the data could be gathered are
      suggested that might help to solve some of these problems in future studies.
      Finally, the advantages and disadvantages of employing alternative methods for
      analyzing multivariate time series data, including dynamic factor analysis, are
      discussed.

PMID- 9615423
TI  - Mad King George: the impact of personal and political stress on mental and
      physical health.
AB  - Both historians and psychiatrists have tried to explain the recurrent attacks of
      mental and physical illness experienced by King George III of Great Britain.
      Although the porphyria hypothesis is widely accepted, this diagnosis assumes that
      the king's breakdowns were not precipitated by extreme stress. This assumption
      was tested using single-case historiometric methods. Biographical data were
      compiled to form two extensive chronologies of the monarch's life, one for
      stressful events and the other for pathological symptoms. From this information
      22 independent judges reliably assessed fluctuations in stress (total, personal,
      and political) and health (total, physical, and mental) across 624 consecutive
      months between 1760 and 1811. The cross-correlations were then calculated for the
      raw, first-differenced, and prewhitened time series. A consistent tendency
      appeared for the king's health to deteriorate after increases in stress, most
      frequently with a 9-month delay. The current study demonstrates the utility of
      applying quantitative techniques to a psychobiographical debate hitherto examined
      solely by qualitative approaches.

PMID- 9615425
TI  - Effects of two MMPI-2 validity scales on basic scale relations to external
      criteria.
AB  - Many clinicians have come to rely on the broad array of validity scales available
      on the MMPI and the MMPI-2. In this study, we evaluated the utility of 2 MMPI-2
      validity scales, the K scale and VRIN scale, in a sample of 692 psychiatric
      inpatients. Specifically, the effects of the K-correction procedure and the
      exclusion of protocols based on VRIN scale elevations were examined on the
      relation between MMPI-2 basic clinical scales and external criteria including
      both self-report and clinician ratings of psychopathology. Results indicated that
      the K-correction procedure commonly used with the MMPI and MMPI-2 did not result
      in higher correlations with external criteria in comparison to non-K-corrected
      scores. In contrast, MMPI-2 protocols that produced VRIN T-score values > or = 80
      generally produced lower correlations with patients self-reports and clinician
      ratings of psychopathology in comparison to protocols judged to be valid based on
      VRIN scale results.

PMID- 9615426
TI  - Long-term stability of MMPI-A scales.
AB  - Adolescents (24 boys, 37 girls) from public school settings were given the MMPI-A
      on 2 occasions with approximately 1 year between testing sessions. Long-term
      stability of validity, clinical, content, supplementary, and the new
      Psychopathology Five scales are examined and correlation coefficients are
      presented. The reliabilities of the MMPI-A scales are consistent with previously
      reported data. In addition, improvements made during development of the MMPI-A
      may have led generally to modest increases in stability of the clinical scales
      for adolescents. Given the importance of both short-term and long-term test
      retest data in the evaluation of the validity of an assessment instrument, this
      study represents an important step in evaluating the validity of the MMPI-A for
      assessment of personality.

PMID- 9615427
TI  - The Estonian Self-Consciousness Scale and its relation to the five-factor model
      of personality.
AB  - The Self-Consciousness Scale (SCS), developed by Fenigstein, Scheier, and Buss
      (1975), was adapted to the Estonian language. In general, the results supported
      the 3-factor structure of the SCS. However, many items in the subscales did not
      load as expected. A 26-item modified scale, the Estonian SCS (ESCS), is
      presented. A joint factor analysis of the ESCS and the NEO Personality Inventory
      (NEO-PI) scales led to a 5-factor solution, where all the factors that emerged
      were identified as the Big Five personality dimensions, the ESCS subscales
      loading most significantly on 3 of these factors: Neuroticism (N), Extraversion
      (E), and Openness to Experience (O). Correlation analysis revealed a pattern of
      correlations, characterized by the strongest associations between Social Anxiety
      and E (r = -.77), Public Self-Consciousness (PubSC) and N (r = .40), and Private
      Self-Consciousness (PrivSC) and O (r = .34), which quite well corresponds to the
      pattern of correlations that was reported for the original versions of the SCS
      and the NEO-PI (Zuckerman, Kuhlman, Joireman, Teta, & Kraft, 1993). We can
      conclude that all the SCS subscales can be sufficiently well interpreted in terms
      of the Big Five model of personality dimensions--PrivSC and PubSC appear to
      describe some variations of the Big Five themes that are not fully elaborated by
      the NEO-PI rather than being completely independent domains of individual
      differences.

PMID- 9615428
TI  - A comparison of three indexes to assess the dimensions of structural analysis of
      social behavior.
AB  - Structural Analysis of Social Behavior (SASB) is an increasingly popular model of
      interpersonal and intrapsychic interactions that provides a flexible assessment
      methodology ranging from an observer-based coding system to a modifiable
      objective self-report questionnaire: the Intrex. Published research using the
      Intrex has varied in the methods employed to assess the fundamental dimensions of
      affiliation and autonomy of SASB. In this article, we review the conceptual and
      computational differences among 3 indexes to assess the SASB dimensions.
      Empirical comparisons revealed good support for convergent validity but
      significant differences in distribution characteristics and orthogonality. These
      results have direct implications for assessment strategies, statistical analyses,
      and interpretation of both clinical assessments and clinical research. Results
      are discussed with reference to developing guidelines for assessment and research
      use of SASB via self-report.

PMID- 9615429
TI  - Measurement of social introversion by the MMPI-2.
AB  - Psychometric characteristics of the Social Introversion (Si) scale, the Social
      Discomfort (SOD) scale, and the Si subscales of the MMPI-2 were examined in
      clinical samples of 122 psychiatric patients and 399 patients with substance-use
      disorders. The combined Si1 (Shyness/Self-Consciousness) and Si2 (Social
      Avoidance) subscales correlated highly with SOD and are apparent measures of the
      social introversion construct. Si3 (Self/Other Alienation) was found to be a
      measure of the general maladjustment factor of the MMPI-2. Content not included
      on the Si subscales was divided into a group of items that measures general
      maladjustment and 2 other item groups that may assess minor constructs related to
      social introversion. As in previous research, the 3 Si subscales accounted well
      for variance in Si scores.

PMID- 9615430
TI  - The MCMI-II and race.
AB  - In this study, we investigated MCMI-II profile differences in a sample of 65
      Black and 164 White psychiatric inpatients. A multivariate analysis of variance
      (MANOVA) yielded a significant multivariate effect associated with race, with
      Black patients scoring significantly higher on the Histrionic, Narcissistic,
      Paranoid, Drug Dependent and Delusional Disorder scales. A second MANOVA was
      conducted on these 5 scales with a smaller sample of 46 Black and 46 White
      patients, who were matched for primary Axis I discharge diagnosis and matched for
      substance abuse comorbidity. This MANOVA did not yield a significant multivariate
      effect associated with race, and scale differences were attenuated.

PMID- 9615431
TI  - Factor structure of the MCMI-III.
AB  - The factor structure of the Millon Clinical Multiaxial Inventory (Millon, 1994;
      MCMI-III) was assessed among 444 African American inpatient substance abusers and
      constitutes the first factor analysis of the MCMI-III. We found 3 main factors:
      General Maladjustment, Paranoid Behavior/Thinking With Detached Emotionality, and
      Antisocial Acting Out. These factors were essentially similar to previous
      findings of factor studies with the MCMI and MCMI-II across diverse populations.
      This factor invariance should lend credibility to the revised test and spur
      additional research into its psychometric properties.

PMID- 9615432
TI  - Aerolysin--a paradigm for membrane insertion of beta-sheet protein toxins?
AB  - The determination of the crystal structure of the bacterial protein proaerolysin
      provided the first view of a pore-forming toxin constructed mainly from beta
      sheet. The structure that was obtained and subsequent crystallographic and
      biochemical studies have together allowed us to explain how the toxin is
      transformed from a water-soluble dimer to a heptameric transmembrane pore. Recent
      discoveries of structural similarities between aerolysin and other toxins suggest
      that the structure/function studies we have made may prove useful in
      understanding the actions of a number of pore-forming proteins.

PMID- 9615433
TI  - General and specific porins from bacterial outer membranes.
AB  - Over the past years, the three-dimensional structures of several bacterial porins
      have been determined to high resolution. Apart from revealing an unusual type of
      architecture, the hollow beta-barrel, they have made it possible to investigate
      in detail various structure-function relationships. Characteristics of ion flow
      through (native and modified) porins inserted into artificial bilayers have been
      related to the electrostatic properties of the pores. The structural basis of
      voltage induced pore closing, however, is still not resolved. The remarkable
      ability of maltoporin to allow translocation of long maltodextrin molecules
      through the small channel has been traced back to the presence of an elongated
      hydrophobic patch at the channel lining.

PMID- 9615434
TI  - alpha-Hemolysin from Staphylococcus aureus: an archetype of beta-barrel, channel
      forming toxins.
AB  - alpha-Hemolysin, secreted from Staphylococcus aureus as a water-soluble monomer
      of 33.2 kDa, assembles on cell membranes to form transmembrane, heptameric
      channels. The structure of the detergent-solubilized heptamer has been determined
      by X-ray crystallography to 1.9 A resolution. The heptamer has a mushroom-like
      shape and measures up to 100 A in diameter and 100 A in height. Spanning the
      length of the molecule and coincident with the molecular sevenfold axis is a
      water-filled channel that ranges in diameter from approximately 16 to
      approximately 46 A. A 14 strand antiparallel beta-barrel, in which two strands
      are contributed by each subunit, defines the transmembrane domain. On the
      exterior of the beta-barrel there is a hydrophobic belt approximately 30 A in
      width that provides a surface complementary to the nonpolar portion of the lipid
      bilayer. The extensive promoter-protomer interfaces are composed of both salt
      links and hydrogen bonds, as well as hydrophobic interactions, and these contacts
      provide a molecular rationalization for the stability of the heptamer in SDS
      solutions up to 65 degrees C. With the structure of the heptamer in hand, we can
      better understand the mechanisms by which the assembled protein interacts with
      the membrane and can postulate mechanisms of assembly.

PMID- 9615435
TI  - 2D crystallization of membrane proteins: rationales and examples.
AB  - The difficulty in crystallizing channel proteins in three dimensions limits the
      use of X-ray crystallography in solving their structures. In contrast, the
      amphiphilic character of integral membrane proteins promotes their integration
      into artificial lipid bilayers. Protein-protein interactions may lead to ordering
      of the proteins within the lipid bilayer into two-dimensional crystals that are
      amenable to structural studies by electron crystallography and atomic force
      microscopy. While reconstitution of membrane proteins with lipids is readily
      achieved, the mechanisms for crystal formation during or after reconstitution are
      not well understood. The nature of the detergent and lipid as well as pH and
      counter-ions is known to influence the crystal type and quality. Protein-protein
      interactions may also promote crystal stacking and aggregation of the sheet-like
      crystals, posing problems in data collection. Although highly promising, the
      number of well-studied examples is still too small to draw conclusions that would
      be applicable to any membrane protein of interest. Here we discuss parameters
      influencing the outcome of two-dimensional crystallization trials using prominent
      examples of channel protein crystals and highlight areas where further
      improvements to crystallization protocols can be made.

PMID- 9615436
TI  - Contributions of electron microscopy and single-particle techniques to the
      determination of the ryanodine receptor three-dimensional structure.
AB  - The ryanodine receptor is the main intracellular calcium release channel from the
      sarcoplasmic reticulum in striated muscle. It is the largest ion channel known,
      composed of four identical major subunits of 565 kDa and four smaller 12-kDa
      subunits, identified as FK-506 binding protein. The successful isolation of the
      ryanodine receptor together with the development of cryoelectron microscopy and
      single-particle image processing techniques have enabled major progress to be
      made in the determination of the receptor's structure over the past decade. Three
      dimensional reconstruction shows the receptor to be composed of two main parts, a
      large square shaped cytoplasmic assembly and a smaller transmembrane assembly.
      The cytoplasmic assembly has an unusual architecture in which about 10 domain
      like structures are interconnected in a loosely packed manner. Subsequent studies
      have started to reveal conformational changes associated with channel gating and
      the localization of binding sites for some proteins with which the receptor
      interacts (calmodulin, and FK-506 binding protein). It is becoming clear that
      long-range induced conformational changes must be involved in the mechanisms of
      modulation of the receptor's gating properties.

PMID- 9615437
TI  - The nicotinic acetylcholine receptor of the Torpedo electric ray.
AB  - The nicotinic acetylcholine receptor is a neurotransmitter-gated ion channel that
      mediates the rapid propagation of electrical signals at the nerve-muscle synapse.
      Its structure at 9 A resolution, in both the closed- and the open-channel forms,
      has been examined by electron microscopy of tubular crystals grown from Torpedo
      postsynaptic membranes. Binding of acetylcholine to open the channel causes a
      localized disturbance in the extracellular domain and initiates small rotations
      of the protein subunits, which trigger a change in configuration of alpha-helices
      lining the membrane-spanning pore. A method recently developed to correct in
      three dimensions for distortions present in the crystals, combined with
      improvements in the electron imaging, should eventually allow these
      conformational changes to be seen at atomic resolution.

PMID- 9615438
TI  - Progress on the structure and function of aquaporin 1.
AB  - Life exists in water as universal solvent, and cells need to deal with its influx
      and efflux. Nature has accomplished the almost impossible, creating membrane
      channels with both a high flux and a high specificity for water. The first water
      channel was discovered in red blood cell membranes. Today known as aquaporin-1,
      this channel was found to be closely related to the major integral protein (MIP)1
      of the eye lens. Cloning and sequencing of numerous related proteins of the MIP
      family revealed the widespread occurrence of such channels, suggesting an
      essential physiological function. Their structures hold the clues to the
      remarkable water channel activity, as well as to the arrangement of transmembrane
      segments in general. Recent medium-resolution three-dimensional electron
      microscopic studies determined a tetrameric complex with six tilted transmembrane
      helices per monomer. The helices within each monomer surround a central density
      formed by two interhelical loops implicated by mutagenesis in the water channel
      function. A combination of sequence analysis and assignment of the observed
      densities to predicted helices provides a basis for speculation on the nature of
      the water course through the protein. In particular, four highly conserved polar
      residues, E142-N192-N76-E17, are proposed to form a chain of key groups involved
      in the pathway of water flow through the channel.

PMID- 9615439
TI  - Conformational changes in the mitochondrial channel protein, VDAC, and their
      functional implications.
AB  - The voltage-dependent, anion-selective channel (VDAC) is generally considered the
      main pathway for metabolite diffusion across the mitochondrial outer membrane. It
      also interacts with several mitochondrial and cytosolic proteins, including
      kinases and cytochrome c. Sequence analysis and circular dichroism suggest that
      the channel is a bacterial porin-like beta-barrel. However, unlike bacterial
      porins, VDAC does not form tight trimeric complexes and is easily gated
      (reversibly closed) by membrane potential and low pH. Circular dichroism
      indicates that the protein undergoes a major conformational change at pH < 5,
      involving decreased beta-sheet and increased alpha-helical content. Electron
      microscopy of two-dimensional crystals of fungal VDAC provides direct information
      about the size and shape of its lumen and suggests that the N-terminal domain
      forms a mobile alpha-helix. It is proposed that the N-terminal domain normally
      resides in a groove in the lumen wall and that gating stimuli favor its
      displacement, destabilizing the putative beta-barrel. Partial closure would
      result from subsequent larger-scale structural rearrangements in the protein,
      possibly corresponding to the conformational change observed at pH < 5.

PMID- 9615440
TI  - Structure of cardiac gap junction intercellular channels.
AB  - Gap junction proteins, termed connexins, constitute a multigene family of
      polytopic membrane channel proteins that have four hydrophobic transmembrane
      domains with the N- and C-termini located on the cytoplasmic membrane face. The
      principal gap junction protein in the heart, alpha 1 connexin (also designated
      Cx43), mediates action potential propagation between cells in order to
      synchronize cardiac contraction. alpha 1 connexin channels are concentrated in
      gap junction plaques located in the intercalated disks. The intercellular channel
      is formed by the docking of two hemi-channels, termed connexons, formed by a ring
      of six 43-kDa alpha 1 connexin subunits. Each subunit is asymmetric with an axial
      ratio of 4-5:1 with approximately 20 A extending into the extracellular gap
      approximately 50 A spanning the lipid bilayer and approximately 50 A extending
      into the cytoplasmic space. We have recently grown two-dimensional crystals of a
      recombinant C-terminal truncation mutant of alpha 1 connexin (designated alpha
      1Cx263T) that are ordered to better than 7 A resolution. Projection density maps
      derived by electron cryocrystallography revealed that the intercellular channel
      is lined by six alpha-helices, and there is a second ring of six alpha-helices at
      the interface with the membrane lipids. These rings of alpha-helices are
      staggered by 30 degrees, which predicts that the two connexons in the channel are
      staggered by 30 degrees such that each connexin subunit in one connexon interacts
      with two subunits in the apposed connexon. Such a quaternary arrangement may
      confer stability in the docking of the connexons to form a tight electrical seal
      for intercellular current flow during cardiac conduction.

PMID- 9615441
TI  - Modelling and simulation of ion channels: applications to the nicotinic
      acetylcholine receptor.
AB  - Molecular dynamics simulations with experimentally derived restraints have been
      used to develop atomic models of M2 helix bundles forming the pore-lining domains
      of the nicotinic acetylcholine receptor and related ligand-gated ion channels. M2
      helix bundles have been used in microscopic simulations of the dynamics and
      energetics of water and ions within an ion channel. Translational and rotational
      motion of water are restricted within the pore, and water dipoles are aligned
      relative to the pore axis by the surrounding helix dipoles. Potential energy
      profiles for translation of a Na+ ion along the pore suggest that the protein and
      water components of the interaction energy exert an opposing effect on the ion,
      resulting in a relatively flat profile which favors cation permeation. Empirical
      conductance calculations based on a pore radius profile suggest that the M2 helix
      model is consistent with a single channel conductance of ca. 50 pS. Continuum
      electrostatics calculations indicate that a ring of glutamate residues at the
      cytoplasmic mouth of the alpha 7 nicotinic receptor M2 helix bundle may not be
      fully ionized. A simplified model of the remainder of the channel protein when
      added to the M2 helix bundle plays a significant role in enhancing the ion
      selectivity of the channel.

PMID- 9615442
TI  - Structural models of the transmembrane region of voltage-gated and other K+
      channels in open, closed, and inactivated conformations.
AB  - A large collaborative, multidisciplinary effort involving many research
      laboratories continues which uses indirect methods of molecular biology and
      membrane biophysics to analyze the three-dimensional structures and functional
      mechanisms of K+ channels. This work also extends to the distant relatives of
      these channels, including the voltage-gated Na+ and Ca2+ channels. The role that
      our group plays in this process is to combine the information gained from
      experimental studies with molecular modeling techniques to generate atomic-scale
      structural models of these proteins. The modeling process involves three stages
      which are summarized as: (I) prediction of the channel sequence transmembrane
      topology, including the functionality and secondary structure of the segments;
      (II) prediction of the relative positions of the transmembrane segments, and
      (III) filling in all atoms of the amino acid residues, with conformations for
      energetically stabilized interactions. Both physiochemical and evolutionary
      principles (including sequence homology analysis) are used to guide the
      development. In addition to testing the steric and energetic feasibilities of
      different structural hypotheses, the models provide guidance for the design of
      new experiments. Structural modeling also serves to "fill in the gaps" of
      experimental data, such as predicting additional residue interactions and
      conformational changes responsible for functional processes. The modeling process
      is currently at the stage that experimental studies have definitely confirmed
      most of our earlier predictions about the transmembrane topology and
      functionality of different segments. Additionally, this report describes the
      detailed, three-dimensional models we have developed for the entire transmembrane
      region and important functional sites of the voltage-gated Shaker K+ channel in
      the open, closed, and inactivated conformations (including the ion-selective pore
      and voltage-sensor regions). As part of this effort, we also describe how our
      development of structural models for many of the other major K+ channel families
      aids in determining common structural motifs. As an example, we also present a
      detailed model of the smaller, bacterial K+ channel from Streptomyces lividans.
      Finally, we discuss strategies for using newly developed experimental methods for
      determining the structures and analyzing the functions of these channel proteins.

PMID- 9615443
TI  - Coevolution of immunoglobulin heavy- and light-chain variable-region gene
      families.
AB  - The gene families encoding the immunoglobulin variable regions of heavy (VH) and
      light (VL) chains in vertebrates are composed of many genes. However, the gene
      number and the extent of diversity among VH and VL gene copies vary with species.
      To examine the causes of this variation and the evolutionary forces for these
      multigene families, we conducted a phylogenetic analysis of VH and VL genes from
      the species of amniotes. The results of our analysis showed that for each
      species, VH and VL genes have the same pattern of clustering in the trees, and,
      according to this clustering pattern, the species can be divided into two groups.
      In the first group of species (humans and mice), VH and VL genes were extensively
      intermingled with genes from other organisms; in the second group of species
      (chickens, rabbits, cattle, sheep, swine, and horses), the genes tended to form
      clusters within the same group of organisms. These results suggest that the VH
      and VL multigene families have evolved in the same fashion: they have undergone
      coordinated contraction and expansion of gene repertoires such that each group of
      organisms is characterized by a certain level of diversity of VH and VL genes.
      The extent of diversity among copies of VH and VL genes in each species is
      related to the mechanism of generation of antibody variety. In humans and mice,
      DNA rearrangement of immunoglobulin variable, diversity, and joining-segment
      genes is a main source of antibody diversity, whereas in chickens, rabbits,
      cattle, sheep, swine, and horses, somatic hypermutation and somatic gene
      conversion play important roles. The evolutionary pattern of VH and VL multigene
      families is consistent with the birth-and-death model of evolution, yet different
      levels of diversifying selection seem to operate in the VH and VL genes of these
      two groups of species.

PMID- 9615444
TI  - Molecular phylogeny and evolution of unique mud-using territorial behavior in
      ocypodid crabs (Crustacea: Brachyura: Ocypodidae).
AB  - Among crabs of the family Ocypodidae, Ilyoplax has been known to exhibit unique
      mud-using territorial behavior against neighbors, including neighbor burrow
      plugging, barricade building, and fence building. To assess the evolution of
      current behavioral forms observed in Ilyoplax, 1,416-bp nucleotide sequences from
      the mitochondrial 12S rRNA to 16S rRNA genes of 20 species, representing four
      recognized subfamilies of Ocypodidae, were analyzed. The resultant phylogenetic
      tree revealed the subfamily Dotillinae, including Ilyoplax, to be monophyletic,
      with a sister group relationship with subfamily Camptandriinae. These two
      subfamilies were branched after Ocypodinae, with Macrophthalminae being most
      basal. Species of Ilyoplax fell into three different Dotillinae lineages,
      indicating the genus to be polyphyletic. Crabs in two of the three lineages
      showed differential geographic distribution and body size. Phylogenetic analyses
      of behavioral characters demonstrated that mud-using techniques had evolved
      multiple times and sequentially. From their behavioral similarity and
      evolutionary occurrence, fence building is hypothesized to have evolved from
      barricade building, and the latter, from burrow plugging. This scenario also
      appeared reasonable with respect to behavioral trends observed in the field. The
      evolution of such territorial behavior is considered to be associated with
      ecological conditions such as burrow fidelity and substrate condition.

PMID- 9615445
TI  - Rates and patterns of mitochondrial DNA sequence evolution in fringilline finches
      (fringilla spp.) and the greenfinch (Carduelis chloris).
AB  - Rates and patterns of evolution in partial sequences of five mitochondrial genes
      (cytochrome b, ATPase 6, NADH dehydrogenase subunit 5, tRNA(Glu), and the control
      region) were compared among taxa in the passerine bird genera Fringilla and
      Carduelis. Rates of divergence do not vary significantly among genes, even in
      comparisons with the control region. Rate variation among lineages is significant
      only for the control region and NADH dehydrogenase subunit 5, and patterns of
      variation are consistent with the expectations of neutral theory. Base
      composition is biased in all genes but is stationary among lineages, and there is
      evidence for directional mutation pressure only in the control region. Despite
      these similarities, patterns of substitution differ among genes, consistent with
      alternative regimes of selective constraint. Rates of nonsynonymous substitution
      are higher in NADH dehydrogenase subunit 5 than in other protein-coding genes,
      and transitions exist in elevated proportions relative to transversions.
      Transitions appear to accumulate linearly with time in tRNA(Glu), and despite
      exhibiting the highest overall rate of divergence among species, there are no
      transversional changes in this gene. Finally, for resolving phylogenetic
      relationships among Fringilla taxa, the combined protein-coding data are broadly
      similar to those of the control region in terms of phylogenetic informativeness
      and statistical support.

PMID- 9615446
TI  - Phylogenetic analysis of the Hsp70 sequences reveals the monophyly of Metazoa and
      specific phylogenetic relationships between animals and fungi.
AB  - To understand the early evolution of the Metazoa, it is necessary to determine
      the correct phylogenetic status of diploblastic animals. Despite cladistic
      studies of morphological characters and recent molecular phylogenetic studies, it
      remains uncertain whether diploblasts are monophyletic or paraphyletic, and how
      the phyla of diploblasts are phylogenetically related. The heat shock protein 70
      (Hsp70) sequences, because of their ubiquity and high degree of conservation,
      could provide a useful model for phylogenetic analysis. We have sequenced almost
      the entire nucleic acid sequence of cytoplasmic Hsp70 from eight diploblastic
      species. Our data support the monophyly of diploblastic animals. However, the
      phylogenetic relationships of the diploblast groups were not significantly
      resolved. Our phylogenetic trees also support the monophyly of Metazoa with high
      bootstrap values, indicating that animals form an extremely robust clade.

PMID- 9615447
TI  - Phylogeny of the Drosophila saltans species group based on combined analysis of
      nuclear and mitochondrial DNA sequences.
AB  - Nucleotide sequences from two nuclear loci, alcohol dehydrogenase and internal
      transcribed spacer-1 of the nuclear ribosomal DNA repeats, and two mitochondrial
      genes, cytochrome oxidase I and cytochrome oxidase II, were determined from nine
      species in the Drosophila saltans species group. The partition homogeneity test
      and partitioned Bremer support were used to measure incongruence between
      phylogenetic hypotheses generated from individual partitions. Individual loci
      were generally congruent with each other and consistent with the previously
      proposed morphological hypothesis, although they differed in level of resolution.
      Since extreme conflict between partitions did not exist, the data were combined
      and analyzed simultaneously. The total evidence method gave a more resolved and
      highly supported phylogeny, as indicated by bootstrap proportions and decay
      indices, than did any of the individual analyses. The cordata and elliptica
      subgroups, considered to have diverged early in the history of the D. saltans
      group, were sister taxa to the remainder of the saltans group. The sturtevanti
      subgroup, represented by D. milleri and D. sturtevanti, occupies an intermediate
      position in this phylogeny. The saltans and parasaltans subgroups are sister
      clades and occupy the most recently derived portion of the phylogeny. As with
      previous morphological studies, phylogenetic relationships within the saltans
      subgroup were not satisfactorily resolved by the molecular data.

PMID- 9615448
TI  - Nuclear receptors, nuclear-receptor factors, and nuclear-receptor-like orphans
      form a large paralog cluster in Homo sapiens.
AB  - We studied a human protein paralog cluster formed by 38 nonredundant sequences
      taken from the Swiss-Prot database and its supplement, TrEMBL. These sequences
      include nuclear receptors, nuclear-receptor factors and nuclear-receptor-like
      orphans. Working separately with both the central cysteine-rich DNA-binding
      domain and the carboxy-terminal ligand-binding domain, we performed
      multialignment analyses that included drawings of paralog trees. Our results show
      that the cluster is highly multibranched, with considerable differences in the
      amino acid sequence in the ligand-binding domain (LBD), and 17 proximal
      subbranches which are identifiable and fully coincident when independent trees
      from both domains are compared. We identified the six recently proposed
      subfamilies as groups of neighboring clusters in the LBD paralog tree. We found
      similarities of 80%-100% for the N-terminal transactivation domain among
      mammalian ortholog receptors, as well as some paralog resemblances within diverse
      subbranches. Our studies suggest that during the evolutionary process, the three
      domains were assembled in a modular fashion with a nonshuffled modular fusion of
      the LBD. We used the EMBL server PredictProtein to make secondary-structure
      predictions for all 38 LBD subsequences. Amino acid residues in the multialigned
      homologous domains--taking the beginning of helix H3 of the human retinoic acid
      receptor-gamma as the initial point of reference--were substituted with H or E,
      which identify residues predicted to be helical or extended, respectively. The
      result was a secondary structure multialignment with the surprising feature that
      the prediction follows a canonical pattern of alignable alpha-helices with some
      short extended elements in between, despite the fact that a number of
      subsequences resemble each other by less than 25% in terms of the similarity
      index. We also identified the presence of a binary patterning in all of the
      predicted helices that were conserved throughout the 38-sequence sample. Our
      results fit well with a recently proposed evolutionary model that combines
      protein secondary structure and amino acid replacement. We propose a new
      hypothesis for molecular evolution, in which chaperones--acting as an endogenous
      cellular device for selection--play a crucial role in preserving protein
      secondary structure.

PMID- 9615449
TI  - Microsporidia, amitochondrial protists, possess a 70-kDa heat shock protein gene
      of mitochondrial evolutionary origin.
AB  - An intronless gene encoding a protein of 592 amino acid residues with similarity
      to 70-kDa heat shock proteins (HSP70s) has been cloned and sequenced from the
      amitochondrial protist Encephalitozoon cuniculi (phylum Microsporidia). Southern
      blot analyses show the presence of a single gene copy located on chromosome XI.
      The encoded protein exhibits an N-terminal hydrophobic leader sequence and two
      motifs shared by proteobacterial and mitochondrially expressed HSP70 homologs.
      Phylogenetic analysis using maximum likelihood and evolutionary distances place
      the E. cuniculi sequence in the cluster of mitochondrially expressed HSP70s, with
      a higher evolutionary rate than those of homologous sequences. Similar results
      were obtained after cloning a fragment of the homologous gene in the closely
      related species E. hellem. The presence of a nuclear targeting signal-like
      sequence supports a role of the Encephalitozoon HSP70 as a molecular chaperone of
      nuclear proteins. No evidence for cytosolic or endoplasmic reticulum forms of
      HSP70 was obtained through PCR amplification. These data suggest that
      Encephalitozoon species have evolved from an ancestor bearing mitochondria, which
      is in disagreement with the postulated presymbiotic origin of Microsporidia. The
      specific role and intracellular localization of the mitochondrial HSP70-like
      protein remain to be elucidated.

PMID- 9615450
TI  - Short repetitive sequences in green algal mitochondrial genomes: potential roles
      in mitochondrial genome evolution.
AB  - Current data on green algal mitochondrial genomes suggest an unexpected dichotomy
      within the group with respect to genome structure, organization, and sequence
      affiliations. The present study suggests that there is a correlation between this
      dichotomy on one hand and the differences in the abundance, base composition, and
      distribution of short repetitive sequences we observed among green algal
      mitochondrial genomes on the other. It is conceivable that the accumulation of GC
      rich short repeated sequences in the Chlamydomonas-like but not Prototheca-like
      mitochondrial genomes might have triggered evolutionary events responsible for
      the distinct series of evolutionary changes undergone by the two green algal
      mitochondrial lineages. The similarity in base composition, nucleotide sequence,
      abundance, and mode of organization we observed between the short repetitive
      sequences present in Chlamydomonas-like mitochondrial genomes on one hand and
      fungal and vertebrate homologs on the other might extend to some of the roles
      that the short repetitive sequences have been shown to have in the latter.
      Potential involvements we propose for the short repetitive sequences in the
      evolution of Chlamydomonas-like mitochondrial genomes include fragmentation and
      scrambling of the ribosomal-RNA-coding regions, extensive gene rearrangements,
      coding-region deletions, surrogate origins of replication, and chromosomal
      linearization.

PMID- 9615451
TI  - Evolution of the vertebrate H1 histone class: evidence for the functional
      differentiation of the subtypes.
AB  - Histone H1 subtypes are involved in chromatin higher-order structure. The
      representation of the subtypes varies greatly depending on the cellular and
      developmental context. We have estimated the rates of nucleotide substitution for
      several H1 subtypes, including mammalian and amphibian H1 degree, avian H5, and
      mammalian H1a-e and H1t, with the aim of finding evidence for their functional
      differentiation. The rates of nonsynonymous substitution differ among the
      subtypes by almost one order of magnitude. Such a wide variation in the degree of
      tolerance of amino acid substitutions is consistent with the functional
      differentiation of the subtypes. H1 has a characteristic three-domain structure.
      The rate ratios among the domains of the molecule are not systematically
      maintained in the different subtypes. This suggests the assumption of
      differentiated functions by the individual domains in chromatin structure. We
      have estimated the average time of divergence of H1a-e and H1t paralogs as 406 +/
      80 Myr. The lack of evidence for concerted evolution of H1a-e and H1t since long
      before the mammalian radiation further supports the functional differentiation of
      the subtypes.

PMID- 9615452
TI  - Nucleotide polymorphism at the alcohol dehydrogenase locus of pocket gophers,
      genus Geomys.
AB  - Using the strictly neutral model as a null hypothesis, we tested for deviations
      from expected levels of nucleotide polymorphism at the alcohol dehydrogenase
      locus (Adh-1) within and among four species of pocket gophers (Geomys bursarius
      major, G. knoxjonesi, G. texensis llanensis, and G. attwateri). The complete
      protein-encoding region was examined, and 10 unique alleles, representing both
      electromorphic and cryptic alleles, were used to test hypotheses (e.g., the
      neutral model) concerning the maintenance of genetic variation. Nineteen variable
      sites were identified among the 10 alleles examined, including 9 segregating
      sites occurring in synonymous positions and 10 that were nonsynonymous. Several
      statistical methods, including those that test for within-species variation as
      well as those that examine variation within and among species, failed to reject
      the null hypothesis that variation (both within and between species of Geomys) at
      the Adh locus is consistent with the neutral theory. However, there was
      significant heterogeneity in the ratio of polymorphism to divergence across the
      gene, with polymorphisms clustered in the first half of the coding region and
      fixed differences clustered in the second half of the gene. Two alternative
      hypotheses are discussed as possible explanations for this heterogeneity: an old
      balanced polymorphism in the first half of the gene or a recent selective sweep
      in the second half of the gene.

PMID- 9615453
TI  - Molecular evolution of olfactomedin.
AB  - Olfactomedin is a secreted polymeric glycoprotein of unknown function, originally
      discovered at the mucociliary surface of the amphibian olfactory neuroepithelium
      and subsequently found throughout the mammalian brain. As a first step toward
      elucidating the function of olfactomedin, its phylogenetic history was examined
      to identify conserved structural motifs. Such conserved motifs may have
      functional significance and provide targets for future mutagenesis studies aimed
      at establishing the function of this protein. Previous studies revealed 33% amino
      acid sequence identity between rat and frog olfactomedins in their carboxyl
      terminal segments. Further analysis, however, reveals more extensive homologies
      throughout the molecule. Despite significant sequence divergence, cysteines
      essential for homopolymer formation such as the CXC motif near the amino terminus
      are conserved, as is the characteristic glycosylation pattern, suggesting that
      these posttranslational modifications are essential for function. Furthermore,
      evolutionary analysis of a region of 53 amino acids of fish, frog, rat, mouse,
      and human olfactomedins indicates that an ancestral olfactomedin gene arose
      before the evolution of terrestrial vertebrates and evolved independently in
      teleost, amphibian, and mammalian lineages. Indeed, a distant olfactomedin
      homolog was identified in Caenorhabditis elegans. Although the amino acid
      sequence of this invertebrate protein is longer and highly divergent compared
      with its vertebrate homologs, the protein from C. elegans shows remarkable
      similarities in terms of conserved motifs and posttranslational modification
      sites. Six universally conserved motifs were identified, and five of these are
      clustered in the carboxyl terminal half of the protein. Sequence comparisons
      indicate that evolution of the N-terminal half of the molecule involved extensive
      insertions and deletions; the C-terminal segment evolved mostly through point
      mutations, at least during vertebrate evolution. The widespread occurrence of
      olfactomedin among vertebrates and invertebrates underscores the notion that this
      protein has a function of universal importance. Furthermore, extensive
      modification of its N-terminal half and the acquisition of a C-terminal SDEL
      endoplasmic-reticulum-targeting sequence may have enabled olfactomedin to adopt
      new functions in the mammalian central nervous system.

PMID- 9615454
TI  - Tie trees generated by distance methods of phylogenetic reconstruction.
AB  - In examining genetic data in recent publications, Backeljau et al. showed cases
      in which two or more different trees (tie trees) were constructed from a single
      data set for the neighbor-joining (NJ) method and the unweighted pair group
      method with arithmetic mean (UPGMA). However, it is still unclear how often and
      under what conditions tie trees are generated. Therefore, I examined these
      problems by computer simulation. Examination of cases in which tie trees occur
      shows that tie trees can appear when no substitutions occur along some interior
      branch(es) on a tree. However, even when some substitutions occur along interior
      branches, tie trees can appear by chance if parallel or backward substitutions
      occur at some sites. The simulation results showed that tie trees occur
      relatively frequently for sequences with low divergence levels or with small
      numbers of sites. For such data, UPGMA sometimes produced tie trees quite
      frequently, whereas tie trees for the NJ method were generally rare. In the
      simulation, bootstrap values for clusters (tie clusters) that differed among tie
      trees were mostly low (< 60%). With a small probability, relatively high
      bootstrap values (at most 70%-80%) appeared for tie clusters. The bias of the
      bootstrap values caused by an input order of sequence can be avoided if one of
      the different paths in the cycles of making an NJ or UPGMA tree is chosen at
      random in each bootstrap replication.

PMID- 9615455
TI  - Analysis of plastid DNA-like sequences within the nuclear genomes of higher
      plants.
AB  - A wide-ranging examination of plastid (pt)DNA sequence homologies within higher
      plant nuclear genomes (promiscuous DNA) was undertaken. Digestion with
      methylation-sensitive restriction enzymes and Southern analysis was used to
      distinguish plastid and nuclear DNA in order to assess the extent of variability
      of promiscuous sequences within and between plant species. Some species, such as
      Gossypium hirsutum (cotton), Nicotiana tabacum (tobacco), and Chenopodium quinoa,
      showed homogenity of these sequences, while intraspecific sequence variation was
      observed among different cultivars of Pisum sativum (pea), Hordeum vulgare
      (barley), and Triticum aestivum (wheat). Hypervariability of plastid sequence
      homologies was identified in the nuclear genomes of Spinacea oleracea (spinach)
      and Beta vulgaris (beet), in which individual plants were shown to possess a
      unique spectrum of nuclear sequences with ptDNA homology. This hypervariability
      apparently extended to somatic variation in B. vulgaris. No sequences with ptDNA
      homology were identified by this method in the nuclear genome of Arabidopsis
      thaliana.

PMID- 9615456
TI  - Molecular evolution of P transposable elements in the genus Drosophila. III. The
      melanogaster species group.
AB  - Phylogenetic relationships were determined for 76 partial P-element sequences
      from 14 species of the melanogaster species group within the Drosophila subgenus
      Sophophora. These results are examined in the context of the phylogeny of the
      species from which the sequences were isolated. Sequences from the P-element
      family fall into distinct subfamilies, or clades, which are often characteristic
      for particular species subgroups. When examined locally among closely related
      species, the evolution of P elements is characterized by vertical transmission,
      whereby the P-element phylogeny traces the species phylogeny. On a broader scale,
      however, the P-element phylogeny is not congruent with the species phylogeny. One
      feature of P-element evolution in the melanogaster group is the presence of more
      than one P-element subfamily, differing by as much as 36%, in the genomes of some
      species. Thus, P elements from several individual species are not monophyletic,
      and a likely explanation for the incongruence between P-element and species
      phylogenies is provided by the comparison of paralogous sequences. In certain
      instances, horizontal transfer seems to be a valid alternative explanation for
      lack of congruence between species and P-element phylogenies. The canonical P
      element subfamily, which represents the active, autonomous transposable element,
      is restricted to D. melanogaster. Thus, its origin clearly lies outside of the
      melanogaster species group, consistent with the earlier conclusion of recent
      horizontal transfer.

PMID- 9615457
TI  - Nucleotide variation in the triosephosphate isomerase (Tpi) locus of Drosophila
      melanogaster and Drosophila simulans.
AB  - DNA sequence variation in a 1.1-kb region including the coding portion of the Tpi
      locus was examined in 25 homozygous third-chromosome lines of Drosophila
      melanogaster, nine lines of Drosophila simulans, and one line of Drosophila
      yakuba. Our data show that the widespread allozyme polymorphism observed in
      cosmopolitan D. melanogaster is due to a glutamic acid substitution occurring in
      a phylogenetically conserved lysine that has been identified as part of the
      "hinged-lid" active site of the enzyme. This observation suggests that the
      replacement polymorphism may have important functional consequences. One
      replacement polymorphism was also observed in D. simulans, although its
      functional relevance is more difficult to assess, since it affects a site that is
      not strongly conserved. This amino acid change in D. simulans is associated with
      a single lineage possessing seven unique silent substitutions, which may be
      indicative of balancing selection or population subdivision. The absence of fixed
      amino acid differences between D. melanogaster and D. simulans and only a single
      difference with D. yakuba suggests that triose phosphate isomerase is under
      strong functional constraint. Silent variation is slightly higher for D.
      melanogaster than for D. simulans. Finally, we outline the general lack of
      evidence for old balanced polymorphisms at allozyme loci in D. melanogaster.

PMID- 9615459
TI  - Selection costs of amino acid substitutions in ColE1 and ColIa gene clusters
      harbored by Escherichia coli.

PMID- 9615458
TI  - Genome size and intron size in Drosophila.

PMID- 9615460
TI  - Differences in evolutionary rates among amino acid classes in the mitochondrial
      genes cytochrome oxidase I and cytochrome oxidase II in Drosophila.

PMID- 9615462
TI  - EMF genes interact with late-flowering genes to regulate Arabidopsis shoot
      development.
AB  - To investigate the genetic mechanisms regulating the transition from vegetative
      to reproductive phase in Arabidopsis, double mutants between two embryonic flower
      (emf) and 12 different late-flowering mutants were constructed and analyzed.
      Double mutants in all combinations displayed the emf phenotypes without forming
      rosettes during early development; however, clear variations between different
      double mutants were observed during late development. fwa significantly enhanced
      the vegetative property of both emf mutants by producing a high number of sessile
      leaves without any further reproductive growth in emf1 fwa double mutants. It
      also produced numerous leaf-like flower structures similar to those in leafy ap1
      double mutant in emf2 fwa double mutants. Nine late-flowering mutants, ft, fca,
      ld, fd, fpa, fe, fy, fha, and fve, caused different degrees of increase in the
      number of sessile leaves, the size of inflorescence, and the number of flowers
      only in weak emf1 and emf2 mutant alleles background. Two late-flowering mutants,
      co and gi, however, had no effect on either emf1 and emf2 mutant alleles in
      double mutants. Our results suggest that FWA function in distinct pathways from
      both EMF genes to regulate flower competence by activating genes which specify
      floral meristem identity. CO and GI negatively regulate both EMF genes, whereas
      the other nine late-flowering genes may interact with EMF genes directly or
      indirectly to regulate shoot maturation in Arabidopsis.

PMID- 9615463
TI  - Growth, pigmentation, and expression of the puf and puc operons in a light
      responding-repressor (SPB)-disrupted Rhodobacter sphaeroides.
AB  - We previously cloned a trans-repressor, SPB, for the puf operon of Rhodobacter
      sphaeroides (Shimada et al. 1996) and revealed that SPB was a putative genetic
      counterpart to HvrA in Rhodobacter capsulatus, a trans-activator for the puf and
      puh operons (Mizoguchi et al. 1997). In this study we constructed a spb-disrupted
      R. sphaeroides, strain L-7, to elucidate the function of SPB. This disruption of
      the spb gene increased the photosynthetic growth rate and the cellular levels of
      photopigments under low-intensity light conditions. The disruption also
      derepressed the expression of the puf and puc operons under high-intensity light
      conditions. In strain L-7, however, strong illumination still reduced the
      cellular levels of photopigments as it did in the wild strain, suggesting that
      SPB did not directly affect the formation of photopigments. These results support
      our previous suggestion that SPB functions as a high-light repressor for puf
      operon in R. sphaeroides in striking contrast to HvrA, which is a low-light
      activator for puf and puh operons in R. capsulatus, even though SPB and HvrA are
      highly homologous. Disruption of spb gene had no effect on the oxygen-mediated
      regulation of the pigmentation or the expression of puf and puc operons.

PMID- 9615461
TI  - Molecular characterisation of the 76 kDa iron-sulphur protein subunit of potato
      mitochondrial complex I.
AB  - Genes encoding subunits of complex I (EC 1.6.5.3) of the mitochondrial
      respiratory chain vary in their locations between the mitochondrial and nuclear
      genomes in different organisms, whereas genes for a homologous multisubunit
      complex in chloroplasts have to date only been found on the plastid genome. In
      potato (Solanum tuberosum L.), the gene coding for the mitochondrial 76 kDa iron
      sulphur protein is identified in the nuclear genome. The gene is transcribed into
      polyadenylated mRNA which is most abundant in flowers, and more frequent in
      tubers than in leaves. The amino acid sequence is well conserved relative to the
      nuclear-encoded 75 kDa and 78 kDa subunits of Bos taurus and Neurospora crassa,
      respectively, and to the Paracoccus denitrificans homologue, most prominently in
      the region presumed to carry the iron-sulphur clusters. Polyclonal antibodies
      directed against the 78 kDa complex I subunit of N. crassa recognise the 76 kDa
      polypeptide in potato mitochondrial complex I, and additionally a polypeptide of
      75 kDa in solubilised stroma thylakoids from spinach chloroplasts. The 32 amino
      acid residues long presequence of the potato mitochondrial 76 kDa complex I
      subunit targets the precursor polypeptide into isolated potato mitochondria but
      not into isolated chloroplasts. These results suggest that chloroplast stroma
      thylakoids contain a protein similar in size and antigenicity to, but genetically
      distinct from, the mitochondrial subunit.

PMID- 9615464
TI  - Patterns of expression of the genes for glutamine synthetase isoforms during
      somatic and zygotic embryogenesis in carrot.
AB  - Three cDNA clones encoding isoforms of carrot glutamine synthetase (GS) were
      isolated and used as probes for analysis of the patterns of expression of the
      genes for GS isoforms during somatic embryogenesis and seed development in
      carrot. Transcripts corresponding to two of the cDNAs, CGS102 and CGS201,
      accumulated in both somatic embryos and developing seeds in the same manner.
      Their levels were high at the early stage of embryogenesis but decreased at the
      late stage. This pattern of expression is similar to the pattern of changes in GS
      activity observed during somatic embryogenesis. In contrast, expression of the
      transcript for another GS isoform detected with CGS103 cDNA was observed at the
      late stage of seed development and in senesced leaves but not in somatic embryos
      or young leaves. We also analyzed the levels of the transcripts in somatic
      embryos that had been cultured in media with either ammonium ions or glutamine as
      the nitrogen source. The amounts of the CGS102 and CGS201 transcripts fell when
      glutamine was supplied in the medium. These results indicated that GS activity
      was regulated at the transcriptional level and that the pattern of expression of
      the genes for GS during somatic embryogenesis reflected that during zygotic
      embryogenesis. It is possible that somatic embryogenesis and zygotic
      embryogenesis have common regulatory systems with respect to nitrogen metabolism.

PMID- 9615466
TI  - Molecular cloning and characterization of aldehyde oxidases in Arabidopsis
      thaliana.
AB  - Using degenerate primers designed by deduced amino acid sequences of known
      aldehyde oxidases (AO) from maize and bovine, two independent cDNA fragments were
      amplified by reverse transcription-polymerase chain reaction (PCR). The two
      corresponding full-length cDNAs (atAO-1 and atAO-2; 4,484 and 4,228 bp long,
      respectively) were cloned by screening the Arabidopsis cDNA library followed by
      rapid amplification of cDNA end-PCR. These cDNAs are highly homologous at both
      the nucleotide and amino acid sequence levels, and the deduced amino acid
      sequences showed high similarity with those of maize and tomato AOs. They contain
      consensus sequences for two iron-sulfur centers and a molybdenum cofactor (MoCo)
      binding domain. In addition, another cDNA having a sequence similar to that of
      the cDNAs was screened (atAO-3; 3,049 bp), and a putative AO gene (AC002376) was
      reported on chromosome 1, which (atAO-4) was distinct from, but very similar to,
      the above three AOs. atAO-1, 2, 3, and 4 were physically mapped on chromosomes 5,
      3, 2 and 1, respectively. These data indicate that there is an AO multigene
      family in Arabidopsis. atAO-1 protein was shown to be highly similar to one of
      the maize AOs in respect to a region thought to be involved in determination of
      substrate specificity, suggesting that they might encode a similar type of AO,
      which could efficiently oxidize indole-3-acetaldehyde to indole-3-acetic acid
      (IAA). atAO-1 and atAO-2 genes were expressed at higher levels in lower
      hypocotyls and roots of the wild-type seedlings, while atAO-3 was slightly higher
      in cotyledons and upper hypocotyls. The expression of atAO-1 was more abundant in
      the seedlings of an IAA overproducing mutant (superroot1; sur1) than in those of
      wild type. atAO-2 and atAO-3 transcripts were rather evenly distributed in these
      seedlings. A possible involvement of atAO genes in phytohormone biosynthesis in
      Arabidopsis is discussed.

PMID- 9615467
TI  - The maize glutamine synthetase GS1-2 gene is preferentially expressed in kernel
      pedicels and is developmentally-regulated.
AB  - The pedicel region of Zea mays kernels contains a unique form of maize glutamine
      synthetase (GS), GSp1. RNA blot analysis using GS gene-specific probes revealed
      that the expression of the GS1-2 gene was specific to the pedicel and that it
      increased in the kernels during development. This pattern of the maize GS1-2 gene
      expression is consistent with the tissue specificity of the GSp1 protein and
      suggests that it encodes the GSp1 isoform of maize GS.

PMID- 9615468
TI  - Mitochondrial DNA mutations and oxidative damage in aging and diseases: an
      emerging paradigm of gerontology and medicine.
AB  - Human mitochondrial DNA (mtDNA) is a multi-copy extra-chromosomal genetic
      element, which is exposed to a high steady-state level of reactive oxygen species
      and free radicals generated by the respiratory chain in mitochondria. Thus, it is
      much more vulnerable to oxidative damage and mutation than is nuclear DNA. In the
      past decade, more than two-dozen mutations of mtDNA have been observed in the
      somatic tissues of aged individuals. Among them, the 4,977 bp and 7,436 bp
      deletions and the A3243G and A8344G point mutations frequently occur and
      accumulate exponentially with age in muscle and other human tissues. These mtDNA
      mutations occur alone or co-exist in old human tissues at relatively low levels
      (< 5%). Aside from mutation, oxidative damage to mtDNA also increases in an age
      dependent manner in human tissues. On the other hand, more than a hundred mtDNA
      mutations have been detected in patients with mitochondrial myopathy and
      encephalomyopathy. The mutant mtDNA often coexists with the wild-type mtDNA in
      affected tissues (a condition termed heteroplasmy). Usually the clinical severity
      of the disease is correlated with the proportion of the mutate mtDNA in the
      target tissues (usually > 80%). The threshold of the mutant mtDNA which is
      required to elicit clinical symptoms varies with different mutations. At the same
      level, large-scale deletions usually cause much more severe pathologies than do
      point mutations. The pattern of distribution of the mutant mtDNA and the energy
      demand of the target tissues are important factors in determining the
      pathological outcome of the mutation. The mutant mtDNA is usually widely
      distributed in the body tissues of the patient, thereby leading to multi-system
      disorders, which are frequently seen in mitochondrial diseases. Although a
      majority of the pathogenic point mutations are maternally transmitted, large
      scale deletions of mtDNA are mostly sporadic. In addition, tandem duplication and
      depletion of mtDNA have also been found in the muscle and other affected tissues
      of elderly subjects and some patients with mitochondrial myopathy. Moreover,
      recent work in our laboratory has shown that oxidative damage to DNA in affected
      tissues is significantly higher than that in normal tissues. It is now
      established that mutation and oxidative damage of mtDNA are contributory factors
      to aging and that at high levels, they cause a fall of ATP supply below the
      threshold of energy needed by affected tissues in patients with mitochondrial
      diseases. These advances have laid the foundation for the development of
      biomedical gerontology and mitochondrial medicine.

PMID- 9615469
TI  - Acute inductive effects on oncogenic proline-directed protein kinase FA/GSK-3
      alpha in NIH 3T3 cells by ethanol and cadmium.
AB  - Exposure of NIH 3T3 cells to 375 mM ethanol at 37 degrees C for 20 min could
      induce a rapid increase in the protein level and cellular activity of oncogenic
      proline-directed protein kinase FA/glycogen synthase kinase-3 alpha (PDPK FA/GSK
      3 alpha), up to approximately 300% of the control level, in a time- and
      concentration-dependent manner. The maximal inductive effect on PDPK FA/GSK-3
      alpha also occurred within 40 min when cells were treated with only 100 mM
      ethanol. Similarly, exposure of NIH 3T3 cells to 100 microM cadmium for 2 h could
      induce a rapid increase in the protein level and cellular activity of PDPK FA/GSK
      3 alpha, up to approximately 250% of the control level, in a time- and
      concentration-dependent manner. The maximal inductive effect on this kinase
      reached within 3 h when cells were treated with only 50 microM cadmium. The
      results demonstrate that PDPK FA/GSK-3 alpha may not represent a constitutively
      active/mitogen-inactivated protein kinase as previously conceived. Taken together
      with the previous report that PDPK FA/GSK-3 alpha is a heat-inducible protein
      kinase, the results further demonstrate that PDPK FA/GSK-3 alpha may represent a
      typical cellular stresses-inducible protein kinase subject to early induction by
      heat, ethanol and cadmium.

PMID- 9615470
TI  - A toxin conjugate containing transforming growth factor-alpha and ricin A
      specifically inhibits growth of A431 human epidermoid cancer cells.
AB  - The inhibitory effect of human epidermoid cancer cells A431 caused by conjugate
      toxin containing transforming growth factor (TGF-alpha) and ricin A was studied.
      TGF-alpha is a protein with 50 amino acids that specifically binds and stimulates
      phosphorylation of cell surface epidermal growth factor receptor (EGFR) and,
      subsequently, triggers cell proliferation. TGF-alpha as a ligand for EGFR is
      internalized upon binding and decomposed within lysosome. Lectin ricin is
      contained in the castor bean plant. The lectin consists of two subunits, ricin A
      and B. Toxic ricin A binds to ribosome and inhibits protein synthesis of target
      cells. In view of the abundance of EGFR in human cancer cells, the receptor
      mediated endocytosis with the conjugate toxin composed of TGF-alpha and ricin A
      was synthesized, purified and tested for growth inhibition in both normal and
      tumor cells. The cytotoxicity of the conjugate was studied within the range of
      10(-12) and 10(-8) M and IC50 was found to be 10(-10) M for human A431 epidermoid
      cells that over-express EGFR. Compared to A431 cells, the brain metastatic
      variant of human Non-Small Cell Lung Cancer (NSCLC) H226Br squamous cells showed
      a reduced inhibitory effect. On the other hand, no inhibitory effect was found
      with other NSCLC cells studied and normal human lung cells because of the fewer
      available EGF binding sites on the surface of the cells. These results indicated
      that the amount of the available EGFR contributes to the cytotoxic effect on
      human cancer cells, thereby demonstrating involvement of the receptor-mediated
      endocytosis of the conjugate. The result from 12labeled EGF-mediated competition
      assay further demonstrated the specific inhibition activity conferred by TGF
      alpha and ricin A conjugation. Due to poor recovery of the chemical conjugation,
      modification in the form of a recombinant toxin is needed for further in-depth
      studies.

PMID- 9615471
TI  - The preparation of RNA-dependent RNA polymerase complex from virus infected
      plants.
AB  - Cucumber mosaic virus (CMV) is an icosahedrion plant virus and contains three
      different single-stranded positive sense genomic RNAs. The very 3' ends of each
      of the genomic RNAs can fold into a tRNA-like structure. Based on the structural
      analysis of the 3' tRNA-like structure of the brome mosaic virus (BMV), we
      superimposed and redrew the 3' tRNA-like structure of CMV. We homogenized virus
      infected or healthy tobacco leaves with polytron and carried out low speed
      centrifugation twice and ultra-centrifugation three times to get detergent
      solubilized membrane bound fractions. We accidentally found that these fractions
      were enriched with a host-encoded RNA-dependent RNA polymerase (RdRp) activity.
      Similar activity could also be found in other plants tested. Alternately, the
      membrane bound fraction could be simply precipitated by low speed centrifugation
      (3,000 g) and high speed ultra-centrifugation (40,000 g). The pellet was then
      suspended in a detergent-containing buffer, after which 25%-55% glycerol gradient
      fractionation was performed. Activity was tested through the incorporation of
      [alpha-32P]UTP using endogenous CMV RNAs as templates on each fraction collected.
      It was found that most of the fractions contained the viral-encoded RNA-dependent
      RNA polymerase. The products of RdRp reaction were found to have a double
      stranded from through further analysis of the RNase protection assay.

PMID- 9615472
TI  - Studying the effect of temperature on microbial growth using multiplicative
      model.
AB  - The specific growth rates of Brochothrix thermosphacta, Listeria monocytogenes,
      Yersinia enterocolitica, Bacillus cereus, Escherichia coli O157:H7, Salmonella
      spp., Staphylococcus aureus and Clostridium perfringens at various temperatures
      were taken from the Food MicroModel database, and the data sets of specific
      growth rate versus temperature were fitted using the multiplicative model (r = a
      Td, r = specific growth rate; T = temperature; a, d = regression parameters). The
      exponential d-value derived from microbial growth at suboptimum temperatures
      reflected the effectiveness of temperature in enhancing growth. A microorganism
      with a large d-value exhibited a large increment of growth rate as temperature
      increased. The d-value of a microorganism was related to the temperature range
      for growth. The temperature range for the growth of psychrotrophs was usually
      narrow for B. thermosphacta and Y. enterocolitica; hence the d-values of these
      two psychrotrophs were close to 1 whereas d-values of mesophiles, such as B.
      cereus, E. coli O157:H7, Salmonella spp., and S. aureus, were 2.31-2.90, and the
      d-value of C. perfringens, a thermophile, was 3.29. The values of parameter a of
      the model were affected by extra salt added into cultures. For all the strains
      mentioned above, the a-values decreased when the cultures contained higher levels
      of salt. The lowering of the a-value implied that the influence of temperature on
      the growth rate in the model was reduced. The change of the d-value was dependent
      on the capability of the microorganism to overcome the obstacle to growth and was
      affected by the composition of the nutrients and by inhibitory factors in the
      culture. The influence of environmental factors on the d-value was also found in
      Chinese sausages. The d-value of a dominant spoilage strain of Enterococcus sp.
      derived from sausages was 0.833 whereas the d-value derived from MRS cultures was
      2.36. In refrigerated foods which usually contained some preservatives and were
      stored at low temperature, the d-value of psychrotrophic spoilage bacteria was
      around 1. In this case, the linear model could be a reasonable choice for
      predicting the proliferation of spoilage bacteria.

PMID- 9615473
TI  - Maximum likelihood estimation of population divergence times and population
      phylogenies under the infinite sites model.
AB  - In this paper, a maximum likelihood estimator of population divergence time based
      on the infinite sites model is developed. It is demonstrated how this estimator
      may be applied to obtain maximum likelihood estimates of the topology of
      population phylogenies. This approach addresses several classical problems
      occurring in the inference of the phylogenetic relationship of populations, most
      notably the problem of shared ancestral polymorphisms. The method is applied to
      previously published data sets of human African populations and of Caribbean
      hawksbill turtles.

PMID- 9615474
TI  - The population genetics of antibiotic resistance. II: Analytic theory for
      sustained populations of bacteria in a community of hosts.
AB  - The phenomenon of antibiotic resistance is of practical importance and
      theoretical interest. As a foundation for further studies by simulation,
      experiment, and observation, we here develop a mathematical model for the
      dynamics of resistance among the bacteria resident in a population of hosts. The
      model incorporates the effects of natural selection within untreated hosts,
      colonization by bacteria from the environment, and the rapid increase of
      resistance in hosts who receive antibiotics. We derive explicit formulas for the
      distribution of resistance among hosts and for the rise or fall of resistance
      when the frequency of treatment is changed.

PMID- 9615475
TI  - Segregating sites in Wright's island model.
AB  - Expressions for the expectation and variance of the number of segregating sites
      in samples from an island model of population subdivision are derived. For small
      samples, an arbitrary number of demes can be accommodated. Results for larger
      samples are derived under the assumption of an infinite number of demes. However,
      simulations indicate that the latter results will hold quite well for the finite
      island model in many cases. A new estimator of the population migration rate is
      proposed and is shown to outperform the widely used pairwise method.

PMID- 9615476
TI  - Growth-associated synthesis of recombinant human glucagon and human growth
      hormone in high-cell-density cultures of Escherichia coli.
AB  - Synthesis of two recombinant proteins (human glucagon and human growth hormone)
      was investigated in fed-batch cultures at high cell concentrations of recombinant
      Escherichia coli. The glucose-limited growth was achieved without accumulation of
      metabolic by-products and hence the cellular environment is presumed invariable
      during growth and recombinant protein synthesis. Via exponential feeding in the
      two-phase fed-batch operation, the specific cell growth rate was successfully
      controlled at the desired rates and the fed-batch mode employed is considered
      appropriate for examining the correlation between the specific growth rate and
      the efficiency of recombinant product formation in the recombinant E. coli
      strains. The two recombinant proteins were expressed as fusion proteins and the
      concentration in the culture broth was increased to 15 g fusion growth hormone 1(
      1) and 7 g fusion glucagon 1(-1). The fusion growth hormone was initially
      expressed as soluble protein but seemed to be gradually aggregated into inclusion
      bodies as the expression level increased, whereas the synthesized fusion glucagon
      existed as a cytoplasmic soluble protein during the whole induction period. The
      stressful conditions of cultivation employed (i.e., high-cell-density cultivation
      at low growth rate) may induce the increased production of various host-derived
      chaperones and thereby enhance the folding efficiency of synthesized heterologous
      proteins. The synthesis of the recombinant fusion proteins was strongly growth
      dependent and more efficient at a higher specific growth rate. The mechanism
      linking specific growth rate with recombinant protein productivity is likely to
      be related to the change in cellular ribosomal content.

PMID- 9615477
TI  - Microbial oxidative metabolism of diclofenac: production of 4'-hydroxydiclofenac
      using Epiccocum nigrum IMI354292.
AB  - The 4'-hydroxylated metabolite of diclofenac was produced by biocatalysis for
      probing specific human drug-metabolising enzymes (CYP2C9). An initial screen of
      11 microorganisms was carried out (50 ml scale) to identify the organism best
      suited to the regioselective conversion of diclofenac to its 4'-hydroxylated
      metabolite. From this screen, the fungus Epicoccum nigrum IMI354292 was selected
      as the most suitable microorganism. Scale-up was carried out in a 30-l fermenter
      to which 2 g diclofenac was added. After 48 h, 50% of the diclofenac had been
      converted to it 4'-hydroxylated metabolite. The broth was then extracted with
      ethyl acetate and purified by chromatography and crystallisation. This yielded
      0.3 g 4'-hydroxydiclofenac with a purity of at least 99%. The 4'
      hydroxydiclofenac produced by E. nigrum was characterised by HPLC, mass
      spectrometry and NMR.

PMID- 9615478
TI  - Doubly entrapped baker's yeast survives during the long-term stereoselective
      reduction of ethyl 3-oxobutanoate in an organic solvent.
AB  - To attain long-term bioreaction in organic solvents with living microorganisms,
      we tried to protect the microorganisms from the toxicity of the solvent by
      immobilization. In this study, baker's yeast, which is not tolerant to organic
      solvents such as isooctane, was selected as a model microorganism and the
      immobilized living yeast cells were examined for activity in the steroselective
      reduction of ethyl 3-oxobutanoate to ethyl (S)-3-hydroxybutanoate in isooctane;
      an activity that correlated well with the viability of the yeast cells. It was
      found that double entrapment, that is, further entrapment of calcium-alginate-gel
      entrapped cells with a urethane prepolymer, made it possible for the yeast to
      remain viable in isooctane, although other conventional immobilization methods,
      such as single entrapment using polysaccharide or synthetic resin prepolymers,
      were insufficient for its protection. Furthermore, doubly entrapped living yeast
      cells could carry out the stereoselective reduction in isooctane repeatedly for a
      long period (more than 1200 h) with occasional cultivation. Thus, double
      entrapment enabled a microorganism sensitive to organic solvents to survive over
      long-term bioreaction in an organic solvent.

PMID- 9615479
TI  - Secretion, purification, and characterisation of barley alpha-amylase produced by
      heterologous gene expression in Aspergillus niger.
AB  - Efficient production of recombinant barley alpha-amylase has been achieved in
      Aspergillus niger. The cDNA encoding alpha-amylase isozyme 1 (AMY1) and its
      signal peptide was placed under the control of the Aspergillus nidulans
      glyceraldehyde-3-phosphate dehydrogenase (gpd) promoter and the A. nidulans trpC
      gene terminator. Secretion yields up to 60 mg/l were obtained in media optimised
      for alpha-amylase activity and low protease activity. The recombinant AMY1
      (reAMY1) was purified to homogeneity and found to be identical to native barley
      AMY1 with respect to size, pI, and immunoreactivity. N-terminal sequence analysis
      of the recombinant protein indicated that the endogenous plant signal peptide is
      correctly processed in A. niger. Electrospray ionisation/mass spectrometry gave a
      molecular mass for the dominant form of 44,960 Da, in accordance with the loss of
      the LQRS C-terminal residues; glycosylation apparently did not occur. The
      activities of recombinant and native barley alpha-amylases are very similar
      towards insoluble and soluble starch as well as 2-chloro-4-nitrophenol beta-D
      maltoheptaoside and amylose (degree of polymerisation = 17). Barley alpha-amylase
      is the first plant protein efficiently secreted and correctly processed by A.
      niger using its own signal sequence.

PMID- 9615480
TI  - Secretion of the sweet-tasting protein thaumatin by recombinant strains of
      Aspergillus niger var. awamori.
AB  - A recombinant form of the sweet-tasting protein thaumatin has been produced in
      the filamentous fungus Aspergillus niger var. awamori. Expression cassettes
      containing a synthetic gene encoding thaumatin II were prepared and used to
      transform Aspergillus niger var. awamori strain NRRL312. Several fungal strains
      capable of synthesizing and secreting thaumatin into the culture medium were
      generated, and their production capabilities were determined, first in shake
      flasks and later in a laboratory fermentor. We report the expression and
      secretion of thaumatin in concentrations of 5-7 mg/l. This recombinant thaumatin
      is sweet.

PMID- 9615481
TI  - Cloning and expression of Candida guilliermondii xylose reductase gene (xyl1) in
      Pichia pastoris.
AB  - A xylose reductase gene (xyl1) of Candida guilliermondii ATCC 20118 was cloned
      and characterized. The open reading frame of xyl1 contained 954 nucleotides
      encoding a protein of 317 amino acids with a predicted molecular mass of 36 kDa.
      The derived amino acid sequence of C. guilliermondii xylose reductase was 70.4%
      homologous to that of Pichia stipitis. The gene was placed under the control of
      an alcohol oxidase promoter (AOX1) and integrated into the genome of a
      methylotrophic yeast, Pichia pastoris. Methanol induced the expression of the 36
      kDa xylose reductase in both intracellular and secreted expression systems. The
      expressed enzyme preferentially utilized NADPH as a cofactor and was functional
      both in vitro and in vivo. The different cofactor specificity between P. pastoris
      and C. guilliermondii xylose reductases might be due to the difference in the
      numbers of histidine residues and their locations between the two proteins. The
      recombinant was able to ferment xylose, and the maximum xylitol accumulation (7.8
      g/l) was observed when the organism was grown under aerobic conditions.

PMID- 9615482
TI  - High-level expression of the thermoalkalophilic lipase from Bacillus
      thermocatenulatus in Escherichia coli.
AB  - An efficient expression system for the previously only weakly expressed
      thermophilic lipase BTL2 (Bacillus thermocatenulatus lipase 2) was developed for
      the production of large amounts of lipase in Escherichia coli. Therefore, the
      gene was subcloned in the pCYT-EXP1 (pT1) expression vector downstream of the
      temperature-inducible lambda promoter PL. Three different expression vectors were
      constructed: (i) pT1-BTL2 containing the mature lipase gene, (ii) pT1-preBTL2
      containing the prelipase gene and (iii) pT1-OmpABTL2 containing the mature lipase
      gene fused to the signal peptide of the OmpA protein, the major outer membrane
      protein of E. coli. With pT1-BTL2 and pT1-preBTL2, comparable expression levels
      of 7000-9000 U/g cells were obtained independently of the E. coli host. In
      contrast, with E. coli JM105 harbouring pT1-OmpABTL2, 660,000 soluble lipase U/g
      cells was produced, whereas, with E. coli DH5 alpha and BL321, production levels
      of 30,000 U/g cells were achieved. However, most of the lipase remained insoluble
      but active after cell breakage because of the unprocessed OmpA signal peptide. A
      simple cholate extraction followed by proteinase K cleavage and ultrafiltration
      allowed the isolation of 1.15 x 10(6) units of 90% pure mature lipase/wet cells.

PMID- 9615483
TI  - Partial-pKD1 plasmids provide enhanced structural stability for heterologous
      protein production in Kluyveromyces lactis.
AB  - The stability of pKD1-based vectors in the yeast Kluyveromyces lactis was
      investigated during short- and long-term culture. The vectors carried an
      expression/secretion cassette consisting of the Saccharomyces cerevisiae SUC2
      gene under the control of the S. cerevisiae alpha-factor promoter and leader. The
      first set of vectors contained the entire pKD1 sequence linearized at either the
      unique EcoRI or the unique SphI site of the pKD1 plasmid. During long-term
      sequential batch culture in selective medium with either vector, invertase
      activity rapidly dropped while the plasmid-bearing population increased from 60%
      to 100%. This apparently contradictory behavior was due to structural
      instability. The enzyme restriction patterns of recovered plasmid DNA retained
      the pKD1 band while the band containing the SUC2 cassette had decreased
      substantially in size. To overcome this structural instability, a vector carrying
      the pKD1 replication origin and the cis-acting stability locus (lacking the
      inverted repeats) was employed in a pKD1+ (but otherwise isogenic) strain. With
      this plasmid, invertase activity remained constant (for at least 70 generations).
      While the new vector was significantly more stable, initial invertase activity
      was substantially lower than that for the vectors containing the full pKD1
      sequence. Southern hybridization confirmed that this decrease was primarily due
      to reduced copy number. The results indicate that full-pKD1 vectors may be
      preferred for batch culture, while partial-pKD1 vectors are more suitable for
      long-term (e.g., fed-batch or continuous) culture.

PMID- 9615484
TI  - Construction of a food-grade multiple-copy integration system for Lactococcus
      lactis.
AB  - A food-grade vector system was developed that allows stable integration of
      multiple plasmid copies in the chromosome of Lactococcus lactis. The vector
      consists of the plus origin of replication (Ori+) of the lactococcal plasmid
      pWV01, the sucrose genes of the lactic acid bacterium Pediococcus pentosaceus
      PPE1.0 as selectable marker, a multiple-cloning site, and a lactococcal DNA
      fragment of a well-characterized chromosomal region. The system includes two L.
      lactis strains, LL108 and LL302, which produce the pWV01 RepA protein essential
      for replication of the Ori+ vectors. These helper strains allow the construction
      and isolation of the replicating form of the integration plasmids from a
      homologous background. Single-crossover integration of the plasmids in L. lactis
      MG1363 resulted in amplifications to a level of approximately 20
      copies/chromosome after selection of the transformants on medium containing
      sucrose as the only fermentable sugar. The amplifications were stable under
      selective growth conditions. In glucose-containing medium a limited loss of
      integrated plasmid copies was detected at a rate of (7.5-15) x 10(-2) copies per
      generation. One strain, MG124, was isolated that had retained 11 integrated
      copies after a period of 120 generations of non-selective growth. These results
      show that the single-cross-over integration system described here represents a
      simple procedure for the engineering of stable food-grade strains carrying
      multiple copies of a gene of interest.

PMID- 9615485
TI  - Influence of charge variation in the Streptomyces venezuelae alpha-amylase signal
      peptide on heterologous protein production by Streptomyces lividans.
AB  - With the aim of investigating determining factors for secretion of heterologous
      proteins by streptomycetes, we analysed the effect of charge variation in the
      Streptomyces venezuelae ATCC15068 alpha-amylase signal peptide on expression and
      secretion of mouse tumour necrosis factor alpha (mTNF) by Streptomyces lividans.
      To this end, the mTNF cDNA was fused to the wild-type alpha-amylase (aml) signal
      sequence and the fusion gene was expressed under the control of the S. venezuelae
      CBS762.70 subtilisin inhibitor gene (vsi) promoter, which has been shown to be
      very effective in initiating transcription. In addition, the number of positive
      charges in the N region of the alpha-amylase signal peptide was altered by in
      vitro mutagenesis. Secreted and intracellular mTNF levels were determined by
      sodium dodecyl sulphate/polyacrylamide gel electrophoresis and biological
      activity measurements. This revealed moderate amounts of secreted mTNF compared
      to the levels obtained in previous experiments using the vsi promoter in
      combination with the Vsi signal peptide. Levels of secreted mTNF could be
      increased sevenfold by introducing one extra positive charge in the N region of
      the signal peptide.

PMID- 9615486
TI  - Activity-dependent fluorescent labeling of bacteria that degrade toluene via
      toluene 2,3-dioxygenase.
AB  - Alternative substrates for the toluene 2,3-dioxygenase pathway of several
      pseudomonads served as enzyme-activity-dependent fluorescent probes for the
      bacteria. Phenylacetylene and cinnamonitrile were transformed to fluorescent and
      brightly colored products by Pseudomonas putida F1, Pseudomonas fluorescens
      CFS215, and Burkholderia (Pseudomonas) strain JS150. Active bacteria transformed
      phenylacetylene, producing bright yellow solutions containing the putative
      product 2-hydroxy-6-oxo-7-octyn-2,4-dienoate. Transformation of cinnamonitrile
      resulted in bright orange solutions due to accumulation of the putative product 2
      hydroxy-6-oxo-8-cyanoocta-2,4,7-trienoate. Chemical and physical properties of
      the products supported their identification, which indicated that the first three
      enzymes of the pathway catalyzed product formation. Phenylacetylene labeled
      bacteria with green fluorescence emission; bacteria were concentrated on black
      0.2-micron-pore-size polycarbonate filters containing polyvinylpyrrolidone (PVP)
      as a wetting agent. Bacteria labeled with cinnamonitrile were fluorescent orange;
      labeling was effective with bacteria trapped on PVP-free polycarbonate filters.
      Production of the enzymes involved in labeling of P. putida F1 and P. fluorescens
      CFS215 was induced by growth (on arginine) in the presence of toluene; cells
      grown on arginine without toluene were not labeled. Labeling of P. putida F1 by
      phenylacetylene was inhibited by toluene, indicating that the same enzymatic
      pathway was required for transformations of both substrates. Bacteria expressing
      other toluene-degrading enzymatic pathways were not fluorescently labeled with
      phenylacetylene.

PMID- 9615487
TI  - Kinetics of biodegradation of gasoline and its hydrocarbon constituents.
AB  - Aerobic biodegradation of gasoline and its constituents, benzene, toluene and
      ethylbenzene were studied by an enrichment from soil indigenous microbial
      population. The enrichment culture completely degraded 16.1-660 mg/l gasoline in
      2.5-16 days respectively, without accumulation of any by-products. The kinetics
      of gasoline as well as benzene, toluene and ethylbenzene biodegradation was
      investigated with initial gasoline concentrations of 16.1-62.6 mg/l. The maximum
      specific rates of biodegradation of benzene, toluene and ethylbenzene were 0.12,
      0.38 and 0.19 mg mg biomass-1 day-1 respectively. When benzene and toluene were
      used as sole substrate, the maximum specific rates of their biodegradation were
      62.9 and 16.4 times greater than the corresponding values for a mixture
      (gasoline). The microbial culture was able to mineralize up to 200 mg/l pure
      toluene and benzene. Maximum mineralization efficiencies of benzene and toluene
      were 76.7 +/- 5.1% and 76.8 +/- 1.3% respectively. Self-inhibition and
      competitive inhibition patterns were observed during the biodegradation of
      benzene and toluene alone and in the mixture respectively. The observed kinetics
      was modeled according to Andrews' inhibition model.

PMID- 9615488
TI  - Low-temperature bioremediation of a waste water contaminated with anionic
      surfactants and fuel oil.
AB  - We conducted a laboratory study at 10 degrees C on the biological decontamination
      of the waste water from a garage and car-wash that was contaminated with anionic
      surfactants (57 mg 1(-1)) and fuel oil (184 mg hydrocarbons 1(-1)). The
      indigenous microorganisms degraded both contaminants efficiently after
      biostimulation by an inorganic nutrient supply. After 7 days at 10 degrees C, the
      residual contaminations were 11 mg anionic surfactants 1(-1) and 26 mg
      hydrocarbons 1(-1). After 35 days, only the anionic surfactants had been further
      reduced to 3 mg 1(-1). Bioaugmentation of the unfertilized waste water with a
      cold-adapted inoculum, able to degrade both hydrocarbons (diesel oil) and anionic
      surfactants (sodium dodecyl sulphate), resulted in a significant increase of the
      hydrocarbon biodegradation during the first 3 days of decontamination, whereas
      biodegradation of anionic surfactants was inhibited during the first 21 days
      following inoculation. Bioaugmentation of the nutrient-amended waste water was
      without any effect.

PMID- 9615489
TI  - Evidence for glutamate self-capping within a peptide helix.
AB  - The thermal dependence of the carbonyl carbon chemical shift of each residue in a
      helical peptide may be analyzed in terms of a two-state helix/coil transition.
      Such analyses generate values for the chemical shift of each residue in the
      helical and in the coil conformational ensembles of the peptide. The sequence
      dependence of the difference in these two values, termed the difference chemical
      shift, provides a description of the mean distribution of helicity within the
      helical ensemble. In this report, we improve two aspects of the procedures used
      to analyze prior chemical shift measurements of the helical peptide acetylW
      (EAAAR)3Aamide. The new difference chemical shift values for 16 of the 18
      residues describe a very uniform central helical ensemble with frayed ends.
      However, the difference chemical shift values for the two remaining residues,
      alanines 03 and 08, are significantly diminished relative to this uniform
      distribution. Each of these two alanine residues is located i-4 to a glutamate
      residue. It is suggested that the difference chemical shifts for these two
      alanine residues are diminished by a self-capping interaction within the i + 4
      glutamate residues.

PMID- 9615490
TI  - Conformation and interactions of bioactive peptides from insect venoms: the
      bombolitins.
AB  - Bombolitins are five structurally related heptadecapeptides originally isolated
      from the venom of a bumblebee, acting at membrane level and able to enhance the
      activity of Phospholipase A2. The biological activity of this class of natural
      peptides seems to be related to the their ability to form amphiphilic helical
      structures in the presence of phospholipid aggregates or related membrane model
      systems. We have carried out systematic investigations on a series of bombolitins
      and their synthetic analogs in order to establish the conditions in which
      amphipathic helices are formed and to elucidate the details of the interaction
      with phospholipids and related model systems. We have shown that bombolitins and
      their analogs interact with phospholipid aggregates and detergent micelles
      forming amphiphilic helices. By means of the Langmuir film balance technique,
      coupled with fluorescence microscopy, we have Shown that bombolitins perturbe the
      structure of phospholipid monolayers, forming phase separated peptide domains. In
      aqueous solution, in the absence of detergent or phospholipids, bombolitins form
      oligomeric aggregates with consequent conformational transition from a random
      coil to an alpha-helical structure. In the aggregate structure, evidence was
      obtained that helices are oriented in an antiparallel fashion. In this article we
      summarize the most recent results of conformational studies by CD, NMR and
      computer simulations on a series of bombolitins and retro-, all-D- and all-D
      retro-analogs.

PMID- 9615491
TI  - [Malaria control in tropical Africa. 1956].
AB  - Although spraying with insecticides has caused a spectacular regression in
      malaria in many parts of Africa, it cannot be said that the transmission of the
      disease has been definitely interrupted in any large area on the mainland. There
      is therefore some uneasiness regarding the methods so far adopted and doubts as
      to whether the very considerable expenditure involved is justified. There is,
      moreover, acute anxiety about the possible development of resistance to
      insecticides by the vector anopheles. Fortunately, so far there does not appear
      to be any in Africa, and the author considers that logical aim should be complete
      eradication of malaria before resistance does appear to the powerful insecticides
      now available. Control measures must inevitably be continued indefinitely, but if
      the aim of eradication is achieved, operations could cease and it would be
      possible for anopheles to co-exist with man without transmitting malaria. The
      author points out that before any continent-wide campaign can be begun, there
      are, in addition to the problem of funds, a number of other problems which must
      be carefully studied. Among these are the lack of trained specialized staff at
      all levels, transport difficulties, shortage of water over vast areas in the dry
      season and floods during the rains, the differing habits of the various African
      populations, and the biology of the vector mosquitos. Despite these problems,
      however, the time for concerted action to achieve eradication in Africa draws
      nearer with each succeeding day.

PMID- 9615492
TI  - Commentary: malaria control in the 1990s.
AB  - In May 1955 the Eighth World Health Assembly adopted a Global Malaria Eradication
      Campaign based on the widespread use of DDT against mosquitos and of antimalarial
      drugs to treat malaria and to eliminate the parasite in humans. As a result of
      the Campaign, malaria was eradicated by 1967 from all developed countries where
      the disease was endemic and large areas of tropical Asia and Latin America were
      freed from the risk of infection. The Malaria Eradication Campaign was only
      launched in three countries of tropical Africa since it was not considered
      feasible in the others. Despite these achievements, improvements in the malaria
      situation could not be maintained indefinitely by time-limited, highly
      prescriptive and centralized programmes. Also, vector resistance to DDT and of
      malaria parasites to chloroquine, a safe and affordable drug, began to affect
      programme activities. A global Malaria Control Strategy was endorsed by a
      Ministerial Conference on Malaria Control in 1992 and confirmed by the World
      Health Assembly in 1993. This strategy differs considerably from the approach
      used in the eradication era. It is rooted in the primary health care approach and
      calls for flexible, decentralized programmes, based on disease rather than
      parasite control, using the rational and selective use of tools to combat
      malaria. The implementation of the Global Strategy is beginning to have an impact
      in several countries, such as Brazil, China, Solomon Islands, Philippines,
      Vanuatu, Viet Nam and Thailand. The lesson from these areas is clear: malaria is
      being controlled using the tools that are currently available. The challenge is
      now to apply these tools among vulnerable individuals and groups experiencing
      high levels of morbidity and mortality, particularly in sub-Saharan Africa, for
      which long-term investments are required.

PMID- 9615493
TI  - A flow diagram to facilitate selection of interventions and research for health
      care.
AB  - Decisions about health care should be informed by systematic review of valid
      research evidence on the effects of interventions on health outcomes that matter.
      If systematic review suggests it is likely that a health care intervention does
      more good than harm in some settings, questions must be addressed about the local
      applicability of the intervention, its cost-effectiveness, and feasibility of
      implementation. If systematic review suggests that it is unlikely that an
      intervention does more good than harm in any setting, its use should be
      discouraged, while existing interventions are improved or alternative
      interventions developed. If it is uncertain whether an intervention does more
      good than harm, further analysis of existing data or new controlled trials are
      required. The article contains a flow diagram, which provides a structure for
      making such decisions.

PMID- 9615494
TI  - Efficacy and safety of liposomal amphotericin B (AmBisome) for visceral
      leishmaniasis in endemic developing countries.
AB  - Reported are the results of a study to determine the efficacy and safety of
      liposomal amphotericin B (AmBisome) for treating visceral leishmaniasis (kala
      azar) in several developing countries where the disease is endemic (Brazil,
      India, and Kenya). At each study site, sequential cohorts of 10 patients each
      were treated with AmBisome at a dose of 2 mg.kg-1.day-1 (2 MKD). The first cohort
      received regimen 1:2 MKD on days 1-6 and day 10 (total dose: 14 mg/kg). If the
      efficacy with this regimen was satisfactory, a second cohort received regimen 2:2
      MKD on days 1-4 and 10 (total dose: 10 mg/kg); and a third cohort received
      regimen 3:2 MKD on days 1, 5, and 10 (total dose: 6 mg/kg). In India, regimens 1,
      2, and 3 (which were studied concurrently) each cured 100% of 10 patients. In
      Kenya, regimen 1 cured all 10 patients, regimen 2 cured 90% of 10 patients, but
      regimen 3 cured only 20% of 5 patients. In Brazil, regimen 1 was only partially
      curative: 5 of 13 patients (62%). Therefore, 15 patients were administered
      regimen 4 (2 MKD for 10 consecutive days; total dose, 20 mg/kg) and 13 patients
      were cured (83%). These results suggest that for the treatment of kala-azar the
      following doses of AmBisome should be administered: in India and Kenya, 2 mg/kg
      on days 1-4 and day 10; and in Brazil, 2 mg/kg on days 1-10.

PMID- 9615495
TI  - Malaria in the African highlands: past, present and future.
AB  - Many of the first European settlers in Africa sought refuge from the heat and
      diseases of the plains by moving to the cool and salubrious highlands. Although
      many of the highlands were originally malaria free, there has been a progressive
      rise in the incidence of the disease over the last 50 years, largely as a
      consequence of agroforestry development, and it has been exacerbated by scarce
      health resources. In these areas of fringe transmission where the malaria pattern
      is unstable, epidemics may be precipitated by relatively subtle climatic changes.
      Since there is little immunity against the disease in these communities,
      outbreaks can be devastating, resulting in a substantial increase in morbidity
      and death among both children and adults. We present here the results obtained
      using a mathematical model designed to identify these epidemic-prone regions in
      the African highlands and the differences expected to occur as a result of
      projected global climate change. These highlands should be recognized as an area
      of special concern. We further recommend that a regional modelling approach
      should be adopted to assess the extent and severity of this problem and help
      improve disease surveillance and the quality of health care delivered in this
      unstable ecosystem.

PMID- 9615496
TI  - Epidemiology of tetanus in the Marches Region of Italy, 1992-95.
AB  - Reported is the incidence of tetanus in the Marches Region of Italy for the
      period 1992-95. Data were obtained from both the regional public health
      committee's notification forms for infectious diseases and from hospital clinical
      records. A total of 36 cases were examined, comprising 7 males (19.4%) and 29
      females. The raw annual incidence was 6.3 per million population; the
      standardized incidence for females was four times greater than that for males
      (9.2 and 2.4 per million population annually, respectively). The patients' ages
      varied from 31 years to 88 years (median, 73.5 years). The incidence among
      subjects older than 65 years was approximately ten times greater than that among
      younger individuals. Chronic wounds, such as trophic lesions, represented the
      site of tetanus infection in 14.3% of cases whose infection entry point was
      identified. Treatment of the 36 cases required a total of 1239 hospital days, of
      which 58.7% were in intensive care and 29.6% were in infectious diseases
      departments. The raw annual mortality rate for the period considered was 0.7 per
      million population; the case-fatality ratio was 11%. The results of our study
      confirm the limits of the current Italian immunization programmes, which exclude
      a large portion of the population from antitetanus protection.

PMID- 9615497
TI  - Surveillance of acute flaccid paralysis in The Netherlands, 1992-94.
AB  - Detection and investigation of all cases of acute flaccid paralysis (AFP) in
      children below 15 years of age are among the criteria for poliomyelitis-free
      certification. In the absence of poliomyelitis the incidence of AFP is around 1
      per 100,000 children aged < 15 years. In the Netherlands, surveillance of AFP
      began in October 1992 under the supervision of the Dutch Paediatric Surveillance
      System (NSCK). Over 90% of clinically active paediatricians participated in the
      monthly reporting of new cases of AFP. From October 1992 to December 1994 (27
      months), 52 cases of AFP were reported. The incidence was 0.7 per 100,000 over
      the period, and reported cases were evenly distributed throughout the country.
      The main cause of AFP was Guillain-Barre syndrome. The average time between onset
      of symptoms and visiting a doctor was less than 3 days. The median reporting
      delay was 29 days, although the system was not intended as surveillance for
      action. Virological examination of faeces was carried out for only 40.4% of AFP
      patients. The start of the NSCK surveillance system coincided with the 1992-93
      outbreak of poliomyelitis in the Netherlands, but only 7 of the 18 children with
      paralytic poliomyelitis were reported through the AFP surveillance system. For
      certification purposes, the present AFP surveillance system in the Netherlands
      needs to be improved with respect to coverage by including neurologists, rapidity
      of reporting, and completeness of laboratory investigations.

PMID- 9615499
TI  - Trends in low birth weight: a comparison of two birth cohorts separated by a 15
      year interval in Ribeirao Preto, Brazil.
AB  - The incidence and some determinants of low birth weight (LBW) were studied in two
      population-based cohorts of singletons born live to families in Ribeirao Preto,
      Sao Paulo State, Brazil. The first cohort comprised infants born between June
      1978 and May 1979 (6750 births--population survey) and the second, infants born
      between May and August 1994 (2990 births--sample survey). The incidence of LBW
      was 7.2% in 1978-79 and 10.6% in 1994. After adjustment for confounding factors,
      the following determinants remained significant in 1978-79: female sex, maternal
      age > or = 35 years, preterm delivery, < four antenatal health visits, maternal
      smoking, lower level of maternal education, and manual work/unemployment. In
      1994, the significant determinants were preterm delivery, maternal smoking and
      caesarean section. The adjusted percentage population attributable risk (PAR%)
      fell for the majority of risk factors but increased for caesarean section,
      preterm birth, multiparity (> or = 5), primiparity and non-cohabitation. The
      increase in the rate of LBW from 1978-79 to 1994 was higher for families with
      more qualified occupations, and occurred only for infants delivered at 36-40
      weeks' gestational age and weighing 1500-2499 g, i.e. those most likely to be
      born by elective caesarean section. The caesarean section rate rose from 30.3% in
      1978-79 to 51.1% in 1994. The increase in LBW was probably due to iatrogenic
      practices associated with elective caesarean section.

PMID- 9615498
TI  - A single dose of live oral cholera vaccine CVD 103-HgR is safe and immunogenic in
      HIV-infected and HIV-noninfected adults in Mali.
AB  - Despite considerable experience with single-dose, live, oral cholera vaccine CVD
      103-HgR in Asia, Europe, and the Americas, the vaccine had not been evaluated in
      sub-Saharan Africa or on individuals infected with human immunodeficiency virus
      (HIV). We therefore conducted a randomized, placebo-controlled, double-blind,
      cross-over clinical trial in 38 HIV-seropositive (without clinical acquired
      immunodeficiency syndrome (AIDS)) and 387 HIV-seronegative adults in Mali to
      assess its safety and immunogenicity. Adverse reactions (fever, diarrhoea and
      vomiting) were observed with similar frequency among vaccine and placebo
      recipients. The vaccine strain was not isolated from the coprocultures of any
      subject. The baseline geometric mean titre (GMT) of serum vibriocidal antibody
      was significantly lower in HIV-seropositives (1:23) than in HIV-seronegatives
      (1:65) (P = 0.002). Significant rises in vibriocidal antibody were observed in
      71% of HIV-seronegatives and 58% of HIV-seropositives, and in 40% of HIV
      seropositives with CD4+ counts below 500 per microliter. Following immunization,
      the peak vibriocidal GMT in HIV-seronegatives was 1:584 versus 1:124 in HIV
      seropositives (P = 0.0006); in HIV-seropositives with CD4+ counts < 500 per
      microliter, the peak vibriocidal GMT was 1:40 (P = 0.03 versus other HIV
      seropositives). CVD 103-HgR was safe in HIV-infected Malian adults, although
      serological responses were significantly attenuated among HIV-seropositives
      (particularly in those with CD4+ counts < 500 per microliter) relative to HIV
      seronegatives. These results encourage further evaluations of this single-dose,
      oral cholera vaccine in high-risk populations such as refugees in sub-Saharan
      Africa.

PMID- 9615500
TI  - Survey of BCG vaccination policy in Europe: 1994-96.
AB  - A retrospective survey, based on a standardized questionnaire sent to qualified
      public health experts in tuberculosis in 50 European countries, was carried out
      to evaluate the following: concordance between national vaccination programmes
      and WHO recommendations on BCG vaccination for prevention of tuberculosis;
      relation between BCG vaccination and revaccination policy and the tuberculosis
      epidemiological situation; and differences in BCG vaccination policy between
      Western and Central-Eastern European countries. The results obtained (from 41
      (82%) of the 50 countries) revealed that BCG vaccination programmes met WHO
      recommendations in 44% of European countries. Mass primary vaccination and
      general revaccination were extremely common in countries where the prevalence of
      tuberculosis was high. A highly significant difference was found between Western
      and Central-Eastern European countries in terms of their adhesion to WHO
      recommendations. Within Central-Eastern Europe no difference was found between
      countries that had or had not been part of the former Soviet Union. The
      implementation of WHO recommendations into national tuberculosis programmes must
      be intensified, based on the available body of evidence. Preventive methods whose
      cost-effectiveness has not been properly established should be discouraged.

PMID- 9615501
TI  - Outbreak of viral hepatitis B in a rural community in India linked to
      inadequately sterilized needles and syringes.
AB  - In India, virtually all outbreaks of viral hepatitis are considered to be due to
      faeco-orally transmitted hepatitis E virus. Recently, a cluster of 15 cases of
      viral hepatitis B was found in three villages in Gujarat State. The cases were
      epidemiologically linked to the use of inadequately sterilized needles and
      syringes by a local unqualified medical practitioner. The outbreak evolved slowly
      over a period of 3 months and was marked by a high case fatality rate (46.7%),
      probably because of concurrent infection with hepatitis D virus (HDV) or sexually
      transmitted infections. But for the many fatalities within 2-3 weeks of the onset
      of illness, the outbreak would have gone unnoticed. The findings emphasize the
      importance of inadequately sterilized needles and syringes in the transmission of
      viral hepatitis B in India, the need to strengthen the routine surveillance
      system, and to organize an education campaign targeting all health care workers
      including private practitioners, especially those working in rural areas, as well
      as the public at large, to take all possible measures to prevent this often fatal
      infection.

PMID- 9615502
TI  - Unsafe injections.
AB  - In many developing countries use of unsterilized or improperly sterilized needles
      and syringes is common and causes millions of cases of viral hepatitis B and C as
      well as contributing to the spread of human immunodeficiency virus (HIV) and
      other bloodborne pathogens. To combat this problem, WHO has stimulated the
      development of the "auto-destruct" syringe and encourages all donors,
      international agencies, and health departments to include a supply of such
      syringes with all vaccines supplied for emergency purposes. In addition, health
      providers and the public need to be educated about the risk of inappropriate and
      unsterile injections.

PMID- 9615503
TI  - Acute respiratory infections: the forgotten pandemic.

PMID- 9615504
TI  - Canada Communicable Disease Report. Index 1997.

PMID- 9615505
TI  - Quality of life in persons with non-small cell lung cancer: a concept analysis.
AB  - Quality of life, as a concept, has received increased attention in recent years.
      In fact, issues related to quality of life have been identified as among the top
      three priorities for research by the Oncology Nursing Society. Several nurse
      investigators have underscored the importance of quality of life research as an
      outcome measure to evaluate the effectiveness of nursing interventions. Given its
      significance in contemporary nursing practice, a clear understanding of the
      definition and dimensions of quality of life is essential for future development
      of an empirical knowledge base for practice. This article presents a concept
      analysis of quality of life as it relates to the health care of individuals with
      non-small cell lung cancer. An evolutionary method of concept analysis is used as
      a guide for examining the historical context of the concept, defining the
      concept, identifying antecedents, recognizing consequences, and distinguishing
      related concepts. A theoretical model of health-related quality of life is
      proposed on the basis of this analysis, and future directions for research in
      this population are discussed.

PMID- 9615506
TI  - Get real: clinical testing of patients' reading abilities.
AB  - Education of cancer patients is complicated by a number of factors including
      timing, understanding of medical terms, and anxiety-induced inattention. The
      concern about patient education has led to the common practice of providing
      brochures about cancer, responses to cancer, treatment, and management of side
      effects. This material is often written at reading levels that do not match the
      reading ability of the patient. Research has indicated that the stated
      educational level is not equivalent to reading level. Realistic testing of a
      patient's reading ability thus becomes important in choosing the correct
      educational materials. This article reviews seven common available tests and
      discusses in detail the use of the Rapid Estimation of Adult Literacy in Medicine
      (REALM).

PMID- 9615507
TI  - Cytokine-modified tumor vaccines: an antitumor strategy revisited in the age of
      molecular medicine.
AB  - Technological advances and improved understanding of the biology of the immune
      response have resulted in a resurgence of interest in the use of tumor
      vaccination as a means to control cancer. Tumor vaccines genetically modified
      with cytokine genes comprise the greatest proportion of gene therapy approaches
      to cancer. Tumor cells obtained at resection of the primary tumor are grown in
      tissue culture and genetically modified with cytokine genes such that the vaccine
      cells, after injection, may stimulate immune recognition of tumor cells and
      generate immunologic memory to prevent future tumor recurrence. There are many
      unanswered questions regarding tumor vaccination including the optimal dose,
      optimal cytokine, injection technique including route and site of vaccine
      delivery, and methods of evaluating the immune response. Oncology nurses have an
      integral role in these areas as well as in evaluating patients for as yet
      undetermined side effects. As tumor vaccines receive increasing attention by the
      lay media, oncology nurses, especially those in the clinical research setting,
      must learn new terminology and concepts relevant to this new treatment approach
      in order to effectively translate the information to patients.

PMID- 9615508
TI  - The Breast Cancer Prevention Trial: nurses' observations.
AB  - The Breast Cancer Prevention Trial (BCPT), a case study of a clinical prevention
      trial, offered a unique opportunity to examine the multifaceted and complex role
      of the nurse. The primary aims of this study were (a) to identify the self
      descriptions of a sample of nurses involved in the day-to-day management of the
      BCPT, (b) to determine the nurses' perceptions of their own role and the role of
      the women who joined the BCPT, (c) to understand the role of the nurse in the
      larger context of a clinical prevention trial, and (d) to expand the knowledge
      base regarding some of the social and ethical underpinnings of clinical
      prevention trials with healthy participants. The research design was qualitative,
      descriptive, and exploratory. The methods used were the telephone interview and
      the focus group. Fifty BCPT nurses were interviewed. This included 30 telephone
      interviews and 20 additional BCPT nurses who participated in four national and
      international focus groups. After analysis of the data using ethnographic
      methods, a view of the multi-faceted role of the BCPT nurse emerged. On a broader
      scale, the inquiry raised a number of critical ethical and social issues that are
      relevant to future clinical prevention trials with volunteer human participants.

PMID- 9615509
TI  - Living with breast cancer: care givers' perceptions in a surgical ward.
AB  - Caring for women with breast cancer has potential for increasing care giver
      distress and anxiety. Knowledge of the threats implicit in the disease and
      treatment as well as overidentification with the patient form the basis for this
      outcome. In order to describe perceptions of breast cancer as an illness,
      semistructured interviews were carried out with 37 care givers at a surgical
      department. The interviews were tape-recorded and transcribed verbatim. An
      analysis was then carried out of the stories told by the care givers about breast
      cancer as an illness. The results indicated that breast cancer as an illness gave
      rise to predominantly negative and dark associations among the care givers. Their
      experiences of caring for women in critical stages of the illness over many years
      appear to have had a negative influence on them. Death itself, and even more so
      the process leading to the end, were very tangible in their stories. The article
      concludes that care givers on a surgical ward have a fragmented picture of the
      patients and need to be given opportunities to follow the total care process.
      Those care givers who were able to follow the women's stages of illness
      throughout more often had a positive picture.

PMID- 9615510
TI  - Breast restoration decision making: enhancing the process.
AB  - The purpose of this study was to explore the breast restoration decision-making
      patterns used by women who opted to have their breast cancer treated by
      mastectomy. Sixty-four women wearing external breast prostheses and 31 women with
      breast reconstructions were interviewed. Modified versions of Simon's notion of
      "bounded rationality" and Janis and Mann's conflict model provided the conceptual
      scaffolding for the study. Five breast restoration decision-making patterns
      emerged from the analysis of the interview data: (a) Enlightened (actively seeks
      information, considers positive and negative aspects, and demonstrates
      deliberation on the alternatives), (b) Contented (passively accepts minimum
      information on alternatives because of a preference toward a particular type),
      (c) Sideliner (uncritically adopts any alternative that is easy and simple to
      implement), (d) Shifter (gives over the decision to others), and (e) Panic
      stricken (can make no rational decision on alternatives). In the prosthesis
      group, the major pattern used was the Sideliner, and in the reconstruction group
      it was the Contented. None of the participants used the Enlightened pattern. The
      data indicated that there was no evidence of active information-seeking behavior
      or deliberation on the alternatives as part of the women's decision-making
      process. The findings suggest a need for a registered nurse oncology specialist
      to be accessible to women during the period when decisions regarding breast
      restoration are made. This professional has the knowledge to interact effectively
      with these women and serve as their advocate during the decision-making process.
      Implications for professional practice and a model for competent breast
      restoration decision making are presented.

PMID- 9615511
TI  - The meaning of quality of life and the effects of unrelated donor bone marrow
      transplants for chronic myeloid leukemia in adult long-term survivors.
AB  - Qualitative data, as part of a larger study, were collected to assess perceptions
      about quality of life (QOL) after bone marrow transplant (BMT) and its impact on
      long-term survivors who had undergone an unrelated donor bone marrow transplant.
      A sample of 28 survivors participated in the study. Quality of life was described
      in terms of "normality," enjoyment, and fulfillment with life: being
      psychologically and physically healthy, being independent, having family and
      relationships, having work, experiencing happiness, and having material support.
      There were many factors with which survivors found it difficult to cope:
      symptoms, frustration brought from the inabilities to function in life, family
      life, returning to work, and infertility. However, about 25% of the survivors
      reported a positive impact of the BMT on their lives. Main concerns about the
      future were related to health status, the long-term effects of the transplant,
      financial concern, infertility, the normalization process, and the family. These
      data confirmed that unrelated donor BMT patients do not have a different
      perception about their QOL than other BMT patients receiving autologous or
      allogeneic marrow transplants. Some of the issues that differed from the previous
      BMT literature included higher inability to perform daily tasks and dependency on
      others, adverse memories of the transplant, and concerns about the future. These
      areas should be the target of pretransplant interventions and the long-term
      psychosocial services provided to patients. As mentioned by the respondents,
      health care professionals could further improve their patients' QOL by providing
      counseling and psychologic support, education about the effects of the various
      treatments, and improved research in BMT treatment and side effects.

PMID- 9615513
TI  - Attic angioma.

PMID- 9615512
TI  - The meaning of DNR status: oncology nurses' experiences with patients and
      families.
AB  - Patients, providers, and families are increasingly involved in end-of-life
      decisions (advance directives, health care proxy, do-not-resuscitate [DNR] status
      consents). These decisions can be complex processes whereby the participants in
      the process must come to terms with often painful and difficult decisions. The
      role perception of the nurse in end-of-life decision making is not well
      delineated. This chapter explores the results of a study that addresses the
      question, "What are the experiences of oncology nurses as they interact with
      patients and/or family members during the process of patients/families signing
      DNR consents. The grounded theory method of data collection and analysis was used
      to explore this question. The results of the study indicate that central to the
      process of consenting to DNR status is the degree of shared understanding about
      the meaning of DNR status among participants and the conflict that can occur when
      meanings are not shared. A model is presented that illustrates the connections
      between the meanings of DNR (patient, family, and provider) and congruence and
      conflict in the DNR consent process. Strategies are discussed that facilitate
      prevention or resolution of conflict in the DNR status decision-making process.
      Strategies used by the nurse to facilitate decision making by patient and
      families include communicating with, caring for, educating, advocating for, and
      collaborating with patients, families, and other providers.

PMID- 9615514
TI  - Vocal fold hemorrhage following laryngeal trauma.

PMID- 9615515
TI  - Unintended middle turbinectomy during septoplasty.

PMID- 9615516
TI  - Pallister-Hall syndrome.

PMID- 9615517
TI  - Growth rate of acoustic neuromas.

PMID- 9615518
TI  - The safety of allergen immunotherapy: a literature review.
AB  - Allergen immunotherapy is a safe form of therapy with a very low incidence of
      systemic allergic reactions and fatalities. Over the past few years, as a result
      of several investigations, risk factors have been identified, although some
      disagreement remains. Asthmatics, patients on beta-blockers and highly sensitive
      patients are groups at increased risk for systemic reactions. Reactions are more
      common among individuals receiving extracts of pollens, particularly grass and
      ragweed. Most authors have also reported that reactions are more common in
      season. Chest tightness or wheezing, urticaria, pruritus and throat congestion
      were frequent symptoms of severe systemic reactions. The recommendations of
      Greenburg et al (Table 1) and Davis et al (Table 2) serve as valuable guidelines.
      Otolaryngologic allergists have found that home maintenance immunotherapy is a
      safe treatment option (in low-risk patients). In any case, immunotherapy should
      be supervised by a physician well trained in its use and indications, and should
      be administered by personnel trained in the treatment of medical emergencies,
      specifically those related to allergy. This training should include cardiac
      resuscitation. In addition, consideration should be given to premedicating
      patients with antihistamines or corticosteroids and to measuring peak flows prior
      to injection. Because asthmatics are a very high-risk group, it is recommended
      that these patients not undergo immunotherapy at home. In patients who have had
      multiple reactions or in those with severe asthma, consideration should be given
      to discontinuing injections. Finally, optimal or moderate allergen dosing may
      provide the needed balance between therapeutic efficacy and safety.

PMID- 9615519
TI  - Pediatric mucoepidermoid carcinoma of the minor salivary glands.
AB  - Carcinoma of the minor salivary glands is an uncommon lesion in children.
      However, due to the greater proportion of malignancies in salivary gland masses
      of children as compared to adults, a high degree of suspicion is warranted.
      Questionable lesions should be biopsied, and a diagnosis aggressively pursued.
      Wide local excision is the treatment of choice for mucoepidermoid carcinoma of
      the minor salivary glands, and radiation therapy should be considered in select
      cases.

PMID- 9615520
TI  - Sphenoclival Rathke's cleft cysts: embryology, clinical appearance and
      management.
AB  - In summary, Rathke's cleft cysts in the extracranial skull base are rare.
      Untreated, they can grow to involve structures in the sphenoclival region or the
      cavernous sinus. Surgical removal via an approach that offers maximal
      visualization and minimal morbidity affords the best treatment for patients with
      such lesions.

PMID- 9615522
TI  - Facial palsy from Masson's vegetant intravascular hemangioendothelioma.
AB  - Masson's vegetant intravascular hemangioendothelioma (VIH) is a rare benign tumor
      that has a propensity for the head and neck but has been overlooked in the
      otolaryngology literature. Herein, we present the first report of facial palsy
      resulting from a small VIH growing in the fundus of the internal auditory canal
      and the labyrinthine segment of the fallopian canal.

PMID- 9615521
TI  - Thallium/technetium subtraction scanning for primary hyperparathyroidism: scan
      sensitivity and effect on operative time.
AB  - Over a ten-year period 26 patients were evaluated by the authors for elevated
      serum calcium and parathormone levels. All patients were clinically asymptomatic
      and were referred for parathyroid evaluation following a diagnosis of
      hypercalcemia made on routine SMA-12 studies. Twenty-four patients had positive
      thallium/technetium subtraction studies; two were suggestive of bilateral
      adenomata, one of which was confirmed at surgery. In two patients both
      thallium/technetium and technetium sestamibi scanning studies were negative.
      These patients were managed medically without surgical exploration. In all
      operative cases the patients remained normocalcemic during a six-month follow-up
      period. Operative times in all cases were less than one hour.

PMID- 9615524
TI  - Lost in cyberspace? An Internet primer: Part I--The basics.

PMID- 9615523
TI  - Life-threatening deep cervical abscess after infiltration of the tonsillar bed
      for tonsillectomy.

PMID- 9615525
TI  - Black milk--an essay on the nature and importance of saying.
AB  - Three types of verbal communication are considered: saying, speaking and talking.
      While speaking covers a topic and talking fills a social void, saying is defined
      here as a communication to a particular person at a certain moment with a
      specific intended meaning or effect. Examples of saying are presented from the
      Bible and the author's interactions in cases of dementia and catatonia, and a
      poem by Celan. Examples are brought to help define the role of the
      psychotherapist in communicating with the depressive world view of his/her
      patients.

PMID- 9615526
TI  - Repetition, repetition compulsion, motivation, interpretation.
AB  - This paper presents three different conceptualizations (interpretations) of the
      phenomenon of "repetition compulsion" in the various psychoanalytic schools that
      refers explicitly to this conception--as return to, return of (reproduction) or
      recreation (transcendental transformation), or as a linear, circular or spiral
      like psychic movement accordingly. The paper analyzes the metapsychological
      assumptions of each mode of interpretation and tries to relate the psychic models
      underlying these conceptions to the questions of psychotherapeutic attitude and
      technique in the clinical situation.

PMID- 9615527
TI  - Sartre's Freud and the future of Sartrean psychoanalysis.
AB  - I describe Sartre's analysis of Freud as an exemplary case study in existential
      psychoanalysis, a kind of anti-psychiatric analysis; in addition Sartre's
      analysis of Freud is a practical critique of the latter's theory. Sartre's
      overall aim is revolutionary, not primarily concerned with healing people; his
      method transcends the traditional aims of psychoanalysis and psychotherapy. The
      paper is divided into four sections: 1) Sartrean Existential Psychoanalysis: An
      explanation of the basic understandings of Sartre's Existentialism and
      Psychoanalysis. 2) Sartre and Anti-psychiatry: An analysis of the relation and
      influence of Sartre's philosophy on R.D. Laing's anti-psychiatry, and a review of
      the contemporary anti-psychiatric practice of the Philadelphia Association. 3)
      Sartre's Case-study of Freud: An exemplary application of Sartrean psychoanalysis
      and a critique of traditional psychoanalysis. 4) Transcending the Boundaries of
      Therapy: A proposal for a radical application of Sartre's philosophy that extends
      beyond the aims of clinical approaches.

PMID- 9615528
TI  - Toys and games in play therapy.
AB  - The present article discusses the difference between play therapy with toys and
      play therapy with games from a psychodynamic point of view. Toys are regarded as
      offering the child an opportunity to develop a variety of transference reactions,
      while games, because of their inherent competitive characteristic, restrain the
      scope of possible transference reactions. The authors claim that therapists
      should consider these eventualities when choosing which games or toys are to be
      available in the therapy room. This choice might determine, in advance, the
      initial characteristics of the patient's transference.

PMID- 9615529
TI  - Dynamic perspectives of paradoxical intervention.
AB  - This paper describes the use of paradoxical intervention with a patient who,
      despite his persistent appeals for help, remained uncooperative. It endeavors to
      show an understanding of the patient's destructiveness as an expression of his
      neediness and envy, which he expresses via his repeated use of projective
      identification and suggests this intervention as a way out. From a dynamic
      perspective the paradoxical intervention encompasses two contrasting aspects: On
      the one hand, it rechannels the patient's destructiveness and envy in a
      beneficial direction. In that sense the intervention fulfills the patient's wish
      for an omnipotent therapist and for painless therapy, while appearing to prevent
      personality change. On the other hand, the intervention interferes with the
      continued use of projective identification, it facilitates the expression of non
      destructive aggression, creates an ambiguity surrounding the question of who is
      in fact in control of the therapy and, finally, it possibly facilitates the
      creation of a potential space. In that sense the paradoxical intervention assists
      in achieving both the experience of separateness and the ability to use
      symbolization. Parallel processes are described in the therapist's
      countertransference.

PMID- 9615530
TI  - Transitional space in the treatment of immigrants.
AB  - This paper illustrates how the dimension of space is an apt arena for immigrant
      patients to play out their separation problems. A continuum is proposed in which
      the extreme ends represent pathological attitudes toward space. Two cases are
      presented to demonstrate how these differential approaches to space result in
      unique ways of dealing with separation and immigration. Treatment of immigrants
      involves the transformation of the therapeutic milieu into a transitional space
      to form a bridge between the patient's native country and current home and a
      potential space to allow patients to create new ways to view themselves and their
      worlds.

PMID- 9615531
TI  - On a shared intergenerational experience--a short-term intervention with a
      Holocaust survivor as part of a lengthy course of therapy.
AB  - The article describes a short-term therapeutic relationship between a Holocaust
      survivor and a younger therapist, whose family members experienced the Holocaust
      themselves. It took place against the background of the patient's complex
      relationships with her parents and brother in the past, with her husband,
      daughters and grandchildren in the present, as well as of traumatic experiences
      during the Holocaust. The author relates in particular to the force and place of
      the thoughts, fantasies, memories and physical sensations that assailed him
      throughout the process in which he formulated the verbal interventions he found
      himself making. The purpose of this article is to emphasize the relational
      aspects of this therapeutic relationship and the fruitful intergenerational
      encounter and its role in shaping the nature of the therapeutic interaction.

PMID- 9615532
TI  - Serotonin antagonists and neuroleptic-induced extrapyramidal symptoms.

PMID- 9615533
TI  - Survival and development of the different life stages of Ixodes scapularis
      (Acari: Ixodidae) held within four habitats on Long Point, Ontario, Canada.
AB  - From November 1989 to April 1993, blood-fed females and unfed adults and nymphs
      of lxodes scapularis Say were maintained in housings within 4 different habitats
      on Long Point, Ontario, Canada, to evaluate the effects of habitat on tick
      development. More fed females survived the winter within the maple forest (75.6%)
      than the cottonwood dune (36.1%), whereas 52.8-62.0% survived the winter within
      the 2 remaining habitats. The proportions of females that laid eggs within the
      maple forest (90.3%), oak savannah (83.9%), and white pine habitats (78.4%) were
      similar and greater than in the cottonwood dune (53.8%). In each habitat and all
      years, females began laying eggs during late April or early May. The time of egg
      deposition was consistent whether females fed in November and overwintered, or
      fed during April of the subsequent year. Significantly more eggs hatched within
      the maple forest (96.4%) and white pine (79.3%) than in the oak savannah (3.8%)
      or cottonwood dune habitats (0.0%). Hatch occurred in mid- to late July each
      year. The proportion of unfed I. scapularis adults that survived the winter was
      not significantly different among the 4 habitats. Unfed adults held in the oak
      savannah and cottonwood dune habitats died by early June, whereas ticks survived
      until late June or early July within the maple forest and white pine habitats.
      Unfed nymphs survived an average of 3.4 mo (range, 0.5-5.5) longer than unfed
      adults. Fed larvae placed in the field from 22 April to 3 July 1992 molted or
      died that year. In contrast, 66.7 and 100% of fed larvae placed in the field
      between 15 and 28 July, and after 28 July, respectively, overwintered before
      molting. More larvae successfully molted before overwintering (46.9%) than did
      those that overwintered (17.9%). The proportion of larvae that successfully
      molted was greatest within the maple forest and least within the cottonwood dune.
      Fed nymphs placed in the field from 22 April to 4 June molted or died in 1992,
      whereas 53.6 and 99.2% of fed nymphs placed in the field between 17 June and 28
      July, and later than 28 July, respectively, overwintered before molting. Over all
      habitats, the proportion of nymphs that molted successfully was similar for those
      that overwintered (43.5%) and those that did not (36.0%). The proportion of
      nymphs that molted successfully was greatest in the maple forest (60.6%) and
      least within the cottonwood dune (13.3%). Differences in seasonal extremes of
      vapor pressure deficits among habitat types were likely responsible for habitat
      specific differences in survival of I. scapularis. Based on observations on
      captive I. scapularis, the life cycle of this tick on Long Point is completed in
      3 or 4 yr.

PMID- 9615534
TI  - Failure to predict abundance of saltmarsh mosquitoes Aedes sollicitans and A.
      taeniorhynchus (Diptera: Culicidae) by using variables of tide and weather.
AB  - Weather and tide variables were used to develop regression models with light trap
      counts of Aedes sollicitans (Walker) and Aedes taeniorhynchus (Wiedemann) from
      1984 to 1995. Rains, tides, and temperatures, both during and preceding the
      sample period, all showed significant correlations with trap counts. These
      multiple regression models forecasted general population levels during 1996 and
      1997, but not the size of the peaks. Therefore, weather alone can predict general
      trends but cannot be used to accurately predict population levels of Ae.
      sollicitans and Ae. taenio-rhynchus.

PMID- 9615535
TI  - Forensic use of Megaselia abdita and M. scalaris (Phoridae: Diptera): case
      studies, development rates, and egg structure.
AB  - Megaselia abdita Schmitz is reported from human corpses in 2 forensic cases in
      Chicago, IL. This fly has not been recorded in the Nearctic region before these
      occurrences. Descriptions of the death scenes and the insect indicators are
      given, as are developmental schedules and descriptions of the eggs of M. abdita
      and Megaselia scalaris (Loew). The presence of either fly on the body, together
      with blowflies or other insects, could contribute to a determination of the
      postmortem interval. Given their predilection for older carrion, these flies
      would be relegated to a secondary forensic role. Phoridae have been shown to be
      primary flies in Okinawa and Panama, and they may occur elsewhere as the only
      insect evidence, especially in sealed apartments inaccessible to large insects.

PMID- 9615536
TI  - Effect of maternal age on offspring quality in tsetse (Diptera: Glossinidae).
AB  - The effects of maternal age on offspring quality were studied in 1 line of
      Glossina palpalis palpalis Robineau-Desvoidy, 1 line of G. p. gambiensis
      Vanderplank, and 3 lines of G. morsitans morsitans Westwood by measuring
      offspring adult size and the duration of puparial period. G. p. gambiensis males
      also were examined for effects of maternal age on fluctuating asymmetry of wing
      veins. The puparial period was shorter in offspring of old females (late
      offspring) than in offspring of young females (early offspring). The difference
      was small but was greater for male than for female offspring. Early male
      offspring were larger than late males. Wing vein fluctuating asymmetry was
      slightly greater in early than in late offspring in G. p. gambiensis. The
      differences between early and late offspring were very small, and we conclude
      that old females produce offspring of marginally lower quality than those
      produced by young females and that these differences are not biologically
      significant.

PMID- 9615537
TI  - Carboxypeptidase B in Anopheles gambiae (Diptera: Culicidae): effects of
      abdominal distention and blood ingestion.
AB  - Carboxypeptidase B (CPB) activity was detected in the guts of strain G-3 of
      Anopheles gambiae (Giles) and Aedes aegypti (L.). Mosquitoes were examined 3-5 d
      after emergence following exposure to 20% sucrose, from 0 to 4 h after feeding on
      a meal of latex beads in saline, and from 0 to 96 h after blood feeding. CPB
      activity was assayed in whole-gut homogenates, including lumenal contents and
      peritrophic matrix, by following the hydrolysis of a substrate specific for CPB
      [3H]-benzoyl-L-Phe-L-Arg. Homogenates were divided into cytosolic plus lumenal
      components and membrane-associated components. Activity levels changed in
      response to feeding, decreasing in response to distention by saline plus latex
      and increasing only in response to blood. Overall, CPB activity was higher in
      unfed An. gambiae than in unfed Ae. aegypti. Detection of CPB activity in the
      peritrophic matrix of both species indicated that this enzyme was secreted
      actively into the gut lumen. In An. gambiae, CPB activity was optimal at pH 8,
      and thiol-type CPB was the predominant form detected. The data indicated that CPB
      in An. gambiae was regulated by both physical and chemical factors.

PMID- 9615538
TI  - Midgut bacteria in Anopheles gambiae and An. funestus (Diptera: Culicidae) from
      Kenya and Mali.
AB  - Field studies in Kenya and Mali investigated the prevalence of bacteria in the
      midguts of malaria vectors, and the potential relationship between gram-negative
      bacteria species and Plasmodium falciparum sporozoites. Midguts were dissected
      from 2,430 mosquitoes: 863 Anopheles funestus Giles and 1,037 An. gambiae s.l.
      Giles from Kenya, and 530 An. gambiae s.l. from Mali. An. funestus had a higher
      prevalence of gram-negative bacteria (28.5%) compared with An. gambiae collected
      in Kenya and Mali (15.4 and 12.5%, respectively). Twenty different genera of
      bacteria were identified by gas chromatography from 73 bacterial isolates from
      mosquito midguts. Pantoea agglomerans (Enterobacter agglomerans) was the most
      common species identified. There was no association between gram-negative
      bacteria in the midgut and P. falciparum sporozoites in field-collected An.
      gambiae s.l. and An. funestus. However, An. funestus females that harbored gram
      positive bacteria were more likely to be infected with sporozoites compared with
      those with no cultivable bacteria or gram negative bacteria in their midguts.
      Habitat-related variation in the prevalence of diverse types of bacteria in
      mosquitoes could influence malaria parasite development in mosquitoes and
      corresponding sporozoite prevalence.

PMID- 9615539
TI  - Isolation of tick-borne encephalitis virus from Ixodes ovatus (Acari: Ixodidae)
      in Japan.
AB  - A case of tick-borne encephalitis (TBE) was found in a farming area located in
      the southern part of Hokkaido, Japan, in 1993. TBE viruses were isolated from
      sentinel dogs in the area where the human case occurred in 1995. Ticks were
      collected in the area by 2 collection methods in 1995 and virus isolation was
      conducted on ticks in 1995 and 1996. Ixodes ovatus Neumann was found to be the
      predominant tick species in the area. In 1996, 2 virus strains were isolated from
      600 I. ovatus ticks (300 females and 300 males), giving the minimum infection
      rate of 0.33% (2 of 600). The 2 virus strains were identified as TBE virus by
      antigenic analysis using monoclonal antibodies and the indirect immunofluorescent
      antibody test. The results showed that I. ovatus was a suspected vector of the
      emerging TBE virus in Hokkaido.

PMID- 9615540
TI  - Phylogeny of species of Triatoma (Hemiptera: Reduviidae) based on mitochondrial
      DNA sequences.
AB  - DNA sequence comparisons of 12S, 16S, and COI mitochondrial DNA (mtDNA) genes
      were used to infer phylogenetic relationships among 8 species of Triatoma [7
      belonging to the infestans complex and T. circummaculata (Stal), a member of a
      different complex based on morphology]. There was remarkable mtDNA similarity
      between T. infestans (Klug) and T. platensis Neiva that can be explained by mtDNA
      introgression. Evolutionary trees were constructed using Panstrongylus megistus
      (Burmeister) as the outgroup. This outgroup gave evidence that the root of the
      group would be between T. vitticeps (Stal) and the rest of the species. The
      placement of T. circummaculata into the middle of the infestans complex is not
      consistent with the morphological classification, suggesting that the current
      systematics of this group does not reflect phylogenetic affinities.

PMID- 9615541
TI  - Response of male Culicoides variipennis sonorensis (Diptera: Ceratopogonidae) to
      carbon dioxide and observations of mating behavior on and near cattle.
AB  - The response of male Culicoides variipennis sonorensis Wirth & Jones to carbon
      dioxide (CO2) was examined at a dairy in the Chino Basin of southern California.
      Males were collected using CDC-type suction traps (no light) during 6 evenings in
      September and October 1995 when C. v. sonorensis were abundant. Traps were baited
      with 1.8 kg of dry ice, 200-350 nulliparous females, or nothing. Greater than 8
      times as many males were captured in CO2-baited suction traps than in either
      female-baited or unbaited traps. Female-baited and unbaited traps did not differ
      in the number of males captured. Observations of mating behavior near and on a
      host calf were made at a nearby dairy. Males swarmed 1-2 m downwind (east) of a
      restrained calf and 0.3-1.0 m above ground level. Males were also observed
      coupled with blood-feeding females on the calf venter (especially umbilicus and
      teats). Virgin female C. v. sonorensis were captured in CO2-baited suction traps
      and by aspiration while they were engorging on the venter of a tethered calf.
      There appear to be at least two mating strategies in this species: mating
      presumably may occur near hosts in male swarms as well as stenogamously on the
      venter of the host. These mating strategies may serve as prezygotic reproductive
      isolating mechanisms between closely related and sometimes sympatric members of
      the C. variipennis complex.

PMID- 9615542
TI  - Comparison of bait cattle and carbon dioxide-baited suction traps for collecting
      Culicoides variipennis sonorensis (Diptera: Ceratopogonidae) and Culex
      quinquefasciatus (Diptera: Culicidae).
AB  - Carbon dioxide-baited suction trap collections were related to simultaneous bait
      cattle collections of Culicoides variipennis sonorensis Wirth & Jones. Trap
      collections varied directly with numbers taken from each of 3 calves. More (3.4x)
      C. v. sonorensis were taken in a trap with 1,000 ml CO2/min versus a trap baited
      with approximately 300 ml/min (matched to calves by weight). Numbers of insects
      taken from three individual calves relative to their equivalent CO2 output did
      not differ, but engorgement of C. v. sonorensis was higher on 1 calf compared
      with the other 2 calves. Up to 281 C. v. sonorensis fed on a calf exposed for 10
      min. More male (7.7x) and female (6.1x) C. v. sonorensis were collected from the
      calf relative to its equivalent amount of CO2. Under conditions described here,
      female C. v. sonorensis caught by a suction trap multiplied by 7.2 approximates
      numbers expected to be caught near a calf. Engorgement of C. v. sonorensis on
      individual calves declined as abundance increased. Culex quinquefasciatus Say was
      collected in equal numbers from the calves and their equivalent CO2 output, and
      none fed on the cattle. Most (85%) C. v. sonorensis in the vicinity of the CO2
      baited suction trap were collected in the catch bag, compared with 26% of Cx.
      quinquefasciatus.

PMID- 9615543
TI  - Resistance to organophosphorus and pyrethroid insecticides in Culex pipiens
      (Diptera: Culicidae) from Tunisia.
AB  - Resistance to the organophosphates temephos and chlorpyrifos, the carbamate
      propoxur, the pyrethroid permethrin, and the organochloride DDT was investigated
      in Tunisian populations of Culex pipiens pipiens (L.) collected between 1990 and
      1996. Resistance to temephos was uniformly low, reaching 10-fold in the most
      resistant population. In contrast, resistance to chlorpyrifos was highly
      variable, reaching the highest level (> 10,000-fold) recorded worldwide. The
      chlorpyrifos-resistant populations also were highly resistant to propoxur. Some
      populations also showed high resistance to permethrin (up to 5,000-fold) and
      moderate resistance to DDT (approximately 20-fold). Bioassays conducted in the
      presence of synergists showed that increased detoxification had only a minor role
      in resistance, although several over-produced esterases known to be involved in
      organophosphate resistance were detected. To better understand the factors
      influencing the distribution of resistance in Tunisia, the polymorphism of genes
      involved in organophosphate resistance (i.e., over-produced esterases and
      insensitive acetylcholinesterase) was investigated in relation to the genetic
      structure of populations studied by analyzing the electrophoretic polymorphism of
      "neutral" genes. Over the area studied, and despite a high level of gene flow,
      resistance genes showed a patchy distribution. Results are discussed in relation
      to the selection pressure caused by insecticide treatments.

PMID- 9615544
TI  - Mosquito feeding-induced enhancement of Cache Valley Virus (Bunyaviridae)
      infection in mice.
AB  - Cache-Valley (CV) virus, an arthropod-borne bunyavirus, recently has emerged as a
      significant veterinary pathogen causing infertility and congenital malformations
      in North American ruminants. To investigate the role of vector feeding on CV
      infection, adult mice were injected subcutaneously with CV, CV and vector thorax
      extract (a source of vector saliva), or CV into the site of intense, noninfected
      mosquito feeding. Mice did not become infected after injection of CV or CV and
      vector saliva, nor did they produce antibodies to CV. However, injection of CV
      into sites of mosquito feeding resulted in viremia and production of anti-CV
      antibody by 2 wk after infection. This enhancement of CV infection resulted after
      feeding by Aedes triseriatus (Say), Ae. aegypti (L.), or Culex pipiens (L.).
      Enhancement occurred when injection was delayed up to 4 h after mosquito feeding,
      but it was not observed when virus injection was performed at a site distant from
      mosquito feeding. These results indicate that arbovirus infection may be enhanced
      by mosquito-vertebrate host interactions and that replication of arboviruses in
      arthropod vectors may not be responsible for increased virulence of infections
      mediated by infected arthropods. Enhanced CV infection in pregnant mice did not
      result in infertility or malformed pups, indicating that the mouse is not a
      suitable model to study CV-induced malformations.

PMID- 9615545
TI  - Host grooming efficiency for regulation of cat flea (Siphonaptera: Pulicidae)
      populations.
AB  - Grooming efficiency was studied by infesting domestic short-hair cats, Felis
      catus L., with known numbers of cat fleas, Ctenocephalides felis felis Bouche,
      then collecting the cat feces and extracting the fleas to determine how many had
      been groomed off, varying the infestation level. Some hosts were found to be
      significantly more efficient at grooming fleas than others, with the best groomer
      removing 17.6% of its flea burden daily, compared with only 4.1% removed by the
      poorest groomer. Cats were more efficient at grooming fleas at infestations of <
      50 fleas and > 150 fleas. Mean on-host flea longevity was 7.8 d.

PMID- 9615546
TI  - Participation of birds (Aves) in the emergence of Lyme disease in southern Maine.
AB  - The contribution of migratory and resident birds to the introduction of Lyme
      disease will vary with the degree to which various species expose themselves to,
      and are infested by, juvenile vector ticks, and their ability to support and
      transmit the infectious agent. To examine the relative contribution of various
      passerine species during the emergence of this disease, we compared the abundance
      and infection rates of the blacklegged tick, Ixodes scapularis Say, removed from
      mist-netted birds with those from live-trapped mice at a coastal study site in
      southern Maine, collected during an 8-yr period in which the range of this tick
      and the incidence of Lyme disease increased in the state. Weekly bird-banding
      sessions using six 12-m Japanese mist nets were carried out from May through
      August 1989-1996. In 1989, 1991 and 1993, mice were live-trapped in a Sherman
      trap grid (7 by 7 m) during five 3-night sessions, June through August; in 1994
      1996, 2 such grids were similarly trapped. Annual adult tick abundance was
      estimated by flagging vegetation. We removed 2,633 juvenile deer ticks from 1,713
      of 1,972 birds examined. Twenty-five of 64 bird species were infested. The
      percentages of birds infested and the rate of infection among removed larvae and
      nymphs increased over the years, but species varied markedly in their ability to
      infect ticks. No infected larvae were removed from catbirds or towhees. The
      larval to nymphal ratio was higher in mice than in birds. Infection rates among
      bird-derived larvae were less than among mice-derived larvae, but increased with
      time. Because of the different ways in which individual species of passerine
      birds contribute to the availability of vector ticks and respond to the agent of
      Lyme disease in emerging areas, further research into host competency and
      borreliacidal mechanisms is needed.

PMID- 9615547
TI  - DNA sequence variation in Dermacentor hunteri and estimated phylogenies of
      Dermacentor spp. (Acari: Ixodidae) in the New World.
AB  - The genus Dermacentor is represented by 12 species in the New World. We sequenced
      a 300-bp portion of the mitochondrial 16S ribosomal DNA gene for 28 individual
      ticks representing 9 of these species and analyzed their phylogenetic
      relationships. Maximum parsimony, distance (neighbor-joining), and maximum
      likelihood were all used to resolve tree topologies. Eleven specimens of
      Dermacentor hunteri Bishopp representing populations across the tick's entire
      geographic range showed negligible genetic variation, with only single base-pair
      differences between each of 5 haplotypes. We found high degrees of bootstrap
      support (66-86%) for monophyly of the genus, but variable support for monophyly
      of species within the genus. D. hunteri, D. occidentalis Marx, and D. variabilis
      (Say) each resolved as a monophyletic taxon (79-99% support). D. andersoni Stiles
      and D. parumapertus Neumann formed a paraphyletic clade (99% support). D.
      albipictus Packard showed substantial intraspecific variation and warrants
      further investigation. D. imitans Warburton was distinct from all other
      Dermacentor spp. on all trees.

PMID- 9615548
TI  - Characterization of modulation of western equine encephalomyelitis virus by Culex
      tarsalis (Diptera: Culicidae) maintained at 32 degrees C following parenteral
      infection.
AB  - Two lines of Culex tarsalis Coquillett genetically selected for low or high
      western equine encephalomyelitis (WEE) virus production (low viral producer [LVP]
      or high viral producer [HVP], respectively) modulated WEE (i.e., decreased the
      concentration of virus to < 10(4) plaque-forming units after intrathoracic
      inoculation). The LVP line modulated WEE more than HVP, and modulation was most
      pronounced at 32 degrees C. At 15 degrees C, viral replication to high titers
      occurred in both lines. When infected LVP were transferred to 15 degrees C after
      4 d extrinsic incubation at 32 degrees C, replication of WEE to high titers did
      not occur. Mosquitoes transferred from 15 degrees C after replication to high
      titers occurred; to 32 degrees C did significantly modulate WEE titer. Incubation
      at 32 degrees C prior to infection had no effect on the degree or timing of WEE
      modulation in both LVP and HVP lines. Most LVP infected following feeding on a
      high dose of WEE had salivary gland infection barriers. Viral modulation by Cx.
      tarsalis was an alphavirus phenomenon, and was not restricted to WEE.

PMID- 9615549
TI  - Multiple isolations of eastern equine encephalitis and highlands J viruses from
      mosquitoes (Diptera: Culicidae) during a 1996 epizootic in southeastern
      Connecticut.
AB  - Thirty-six isolations of eastern equine encephalitis virus were obtained from 8
      species of mosquitoes collected from 5 September through 18 October 1996 during
      an epizootic in southeastern Connecticut. These included Culiseta melanura
      (Coquillett) (19 isolates), Culex pipiens L. (8), Culiseta morsitans (Theobald)
      (3), Aedes sollicitans (Walker) (2), Aedes cantator (Coquillett) (1), Aedes
      trivittatus (Coquillett) (1), Aedes vexans (Meigen) (1), and Coquillettidia
      perturbans (Walker) (1). Isolations from Ae. cantator and Ae. trivittaus are new
      to North American records, and those from Ae. cantator and Ae. sollicitans
      represent the first infections of human-biting, salt-marsh mosquitoes with
      eastern equine encephalitis virus in Connecticut. With one exception, eastern
      equine encephalitis-infected Cs. melanura were found at all sites where eastern
      equine encephalitis virus was isolated. The large number of eastern equine
      encephalitis isolations from Cs. melanura and the collection of infected
      mosquitoes in residential woodlots and coastal salt marshes away from traditional
      red maple or white cedar swamp habitats, reaffirm the importance of local
      populations of this mosquito for viral amplification and dispersal from swamp
      foci. Highlands J virus was more widespread geographically, but fewer isolations
      of this virus were made from fewer species of mosquitoes. These included Cs.
      melanura (8 isolates), Cx. pipiens (5), Ae. vexans (3), Aedes canadensis
      (Theobald) (1), Ae. cantator (1) and Cs. morsitans (1). No human or horse cases
      of eastern equine encephalitis were reported, although this represents the
      largest number of isolations for eastern equine encephalitis ever recovered from
      field-collected mosquitoes in Connecticut.

PMID- 9615550
TI  - Habitat dependence of a parasite-host relationship: flea (Siphonaptera)
      assemblages in two gerbil species of the Negev Desert.
AB  - Flea assemblages of Meriones crassus Sundevall and Gerbillus dasyurus Wagner in
      different habitats in the Negev Highlands of Israel were studied to determine how
      flea abundance and species composition on the same host change among habitats,
      and the environmental parameters determining specific composition of flea
      assemblage. Fleas of the same species parasitizing different hosts responded
      differently to the same set of environmental variables. Spatial distribution of
      fleas on M. crassus was determined by environmental parameters significantly
      stronger than those on G. dasyurus. Flea abundance and species composition on
      both host species changed among habitats. Indirect ordination of flea assemblages
      produced axes that presented spatial components of change in flea composition
      (for M. crassus--Xenopsylla conformis Rothschild versus Xenopsylla ramesis
      Rothschild; for G. dasyurus--Xenopsylla dipodilli Smit versus X. conformis and X.
      ramesis versus X. conformis). Discriminant analyses of flea assemblage on M.
      crassus demonstrated that fleas were segregated along 2 discriminant axes that
      reflected a soil structure and productivity gradient and a contrast between dry
      riverbeds and watershed plains. Ordination of flea assemblages on G. dasyurus
      produced 2 discriminant axes, both presenting a complex gradient of the soil
      structure and the level of primary production.

PMID- 9615551
TI  - Effects of preservation methods, parasites, and gut contents of black flies
      (Diptera: Simuliidae) on polymerase chain reaction products.
AB  - Molecular analysis of biological specimens usually requires extraction of high
      molecular weight DNA free of foreign DNA contaminants. DNA was extracted from
      black flies at different life stages that had been preserved by 4 methods: larvae
      and adults in ethanol, larvae in Carnoy's solution, adults on card-points, and
      adults hand-swatted and sun-dried. Using specific primers for the mitochondrial
      ND4 gene, a 257-bp amplicon was obtained from specimens preserved by ethanol,
      card-point mounting, and sun-drying. Successful amplification often required DNA
      dilutions > or = 1:20 (< 1-10 ng). DNA from specimens preserved in Carnoy's
      solution (ethanol: acetic acid, 3:1) yielded degraded DNA, resulting in fewer
      successful amplications. Parasitic nematodes and, to a lesser extent, gut
      contents resulted in extra products when amplified with randomly amplified
      polymorphic DNA (RAPD) primers. Sufficient DNA was extracted from the head of a
      larva for a successful polymerase chain reaction (PCR), eliminating the need to
      remove the contaminating gut and parasites.

PMID- 9615552
TI  - Blood acquisition and processing by three Anopheles (Diptera: Culicidae) species
      with different innate susceptibilities to Plasmodium falciparum.
AB  - Anopheles freeborni Aitken, An. gambiae Giles, and An. albimanus Weidemann
      exhibit excellent, good, and poor susceptibility to Plasmodium falciparum Welch,
      respectively. To determine why they differ, 5 variables relating to blood-feeding
      behavior and 10 variables associated with bloodmeal processing were evaluated for
      each species. The 3 Anopheles species did not differ in their probing behavior,
      but An. gambiae took 1.7 times longer to complete engorgement than either An.
      freeborni or An. albimanus. No interspecific differences were seen in patterns of
      prediuresis, blood compaction time, midgut pH, bloodmeal clearance, ovarian
      development, and peritrophic matrix formation. In prediuretic fluid and in blood
      obtained from midguts soon after mosquito feeding, erythrocytes were agglutinated
      heavily in An. albimanus, agglutinated moderately in An. freeborni, and
      unagglutinated in An. gambiae. Erythrocyte hemolysis was greatest in An. gambiae.
      The significant differences in patterns of blood-feeding behavior and bloodmeal
      processing among the 3 Anopheles species did not adequately explain interspecific
      differences in susceptibility to P. falciparum. Therefore, the primary mosquito
      related determinants of sporogonic development may operate after bloodmeal
      processing, and during or after the ookinete-to-oocyst developmental transition.

PMID- 9615553
TI  - Searching for Lyme disease in Colombia: a preliminary study on the vector.
AB  - Lyme disease is an infectious multisystemic illness with dermatologic,
      neurologic, cardiac, and rheumatic manifestations. A total of 4,355 ticks was
      collected in Colombia, of which 2,805 were identified as Ixodes spp. The midgut
      contents of 2,600 specimens were fixed on microscope slides and examined by an
      indirect immunofluorescence assay (IFA) using monoclonal antibodies, anti-ospA
      H5332, and anti-flagellin 9724. All of the ticks examined by IFA tested negative.

PMID- 9615554
TI  - Method for collecting Hypoderma spp. (Diptera: Oestridae) larvae from cattle.
AB  - A new method for collecting 3rd-instar Hypoderma lineatum (Villers) and Hypoderma
      bovis (L.) is described. A procedure for carrying out chronobiological and other
      studies involving the life cycle of these flies is included. The larvae are
      collected from cattle using a dressing made of a circle of cardboard attached to
      a piece of tulle similar in color to the coat of the animal. These small cloth
      cages were attached to the animal skin with fast-drying contact glue wherever the
      swellings produced by 2nd- or 3rd-instar Hypoderma spp. had been previously
      detected. Each animal was inspected daily to detect the appearance of new larvae.
      This procedure allows the collection of each emerged larva without contact with
      other larvae and avoids friction of the cloth cages or dressing with the larvae,
      thus reducing larval death and increasing viability of the parasite.

PMID- 9615555
TI  - Triple cage olfactometer for evaluating mosquito (Diptera: Culicidae) attraction
      responses.
AB  - A triple cage olfactometer for evaluating mosquito attraction responses is
      described. The olfactometer is designed for easy access for interior cleaning,
      has a mechanism that allows synchronous operation of the port doors on each cage,
      and requires 0.8 m2 of floor space. It is constructed of clear acrylic, contains
      3 test chambers in a tiered configuration, has paired removable sleeves and
      mosquito traps on each cage, and is equipped with a filtered external air supply
      system that has temperature and relative humidity control.

PMID- 9615556
TI  - Contact toxicity of permethrin-impregnated fabric to Hyalomma anatolicum
      excavatum (Acari: Ixodidae): effects of laundering and exposure and recovery
      times.
AB  - A previous study that documented enhanced host attachment by the camel ticks
      Hyalomma dromedarii Koch after permethrin exposure prompted a similar
      investigation of permethrin effects in H. anatolicum excavatum Koch, an Old World
      hardbacked tick suspected of vectoring human pathogens. Contact toxicity tests
      were conducted with laboratory-colonized male and female H. a. excavatum of the
      same age exposed for periods of 5, 10, 30, and 60 min to each of 5 fabric
      treatments: unwashed/untreated; unwashed and treated; and treated fabric given 1,
      2, or 3 laundry cycles of warm-water detergent machine washing, followed by hot
      air drying. Fabric was tropical weight 100% cotton military uniform. Treated
      fabric was impregnated with permethrin at 0.125 mg (AI)/cm2. Contact toxicity was
      measured immediately after and 24 h after fabric contact as proportion of ticks
      that attached mouthparts to the skin of a host (rabbit) within a 60-min quest
      period and time lapse (minutes) between contact with the host and attachment.
      Attachment response immediately after permethrin contact was exposure time- and
      wash-dependent in both sexes. Proportion of attaching ticks and times to
      attachment were comparable in controls and in groups exposed to all permethrin
      treated fabrics for 5 or 10 min. Contact periods of 30 and 60 min with 0
      wash/treated or 1-wash and treated fabric significantly reduced the frequency of
      attachment and significantly prolonged mean times to attachment. Compared with
      low levels of attachment response observed immediately after fabric contact,
      recovery of attachment response was observed 24 h after exposure in these
      wash/treatment groups, but inhibition was still evident. Permethrin-induced
      intoxication was more pronounced in males than females. Mortality 24 h after
      exposure was only significant among females exposed to 0-wash/treated fabric for
      60 min. There was no evidence of permethrin-mediated stimulation of the
      attachment response in H. a. excavatum.

PMID- 9615557
TI  - Mediation of deet repellency in mosquitoes (Diptera: Culicidae) by species, age,
      and parity.
AB  - Laboratory bioassays assessed differences in the protection time provided by the
      repellent deet (N,N-diethyl-3-methylbenzamide) against 5-d-old nulliparous and 10
      , 15-, and 20-d-old nulliparous and parous female Aedes aegypti (L.), Anopheles
      albimanus (Weidemann), and Anopheles quadrimaculatus Say sensu lato. Mean
      protection time was shortest against An. albimanus (1.6 h) and An.
      quadrimaculatus (1.5 h) and longest against Ae. aegypti (6.5 h), but was not
      significantly influenced by mosquito age or parity. Mean percentage of biting at
      repellent failure time was highest in An. albimanus (14.2%), followed by An.
      quadrimaculatus (7.0%) and Ae. aegypti (2.9%), was higher in parous females
      (10.8%) than in nulliparous females (5.9%), and was highest overall (35%) in 20-d
      old parous An. albimanus. Interaction between mosquito species and parity and
      between parity and age factors, respectively, resulted from a significant
      decrease in percentage of biting by parous An. quadrimaculatus compared with
      other females, and a significant increase in biting by 20-d-old parous females
      compared with other females. The main finding of this study is that repellent
      protection time is unaffected by parity; this is important because parous
      mosquitoes are the primary target of personal-protection measures in disease
      endemic areas. When repellent failure did occur, there was a higher risk of bite
      by old, parous An. albimanus than for any other species, age, or parity grouping
      of females.

PMID- 9615558
TI  - Effect of osteopathic manipulative treatment of length of stay for pancreatitis:
      a randomized pilot study.
AB  - There have been few randomized, controlled studies of the effects of osteopathic
      manipulative treatment (OMT). In this outcomes research study, the authors
      randomly assigned patients with pancreatitis to receive standard care plus daily
      OMT for the duration of their hospitalization (n = 6) or to receive only standard
      care (n = 8). Osteopathic manipulative treatment involved 10 to 20 minutes daily
      of a standardized protocol, using myofascial release, soft tissue, and strain
      counterstrain techniques. Attending physicians were blinded as to group
      assignment. Results indicated that patients who received OMT averaged
      significantly fewer days in the hospital before discharge (mean reduction, 3.5
      days) than control subjects, although there were no significant differences in
      time to food intake or in use of pain medications. These findings suggest the
      possible benefit of OMT in reducing length of stay for patients with
      pancreatitis.

PMID- 9615559
TI  - Churg-Strauss syndrome associated with zafirlukast.
AB  - In recent years, the leukotriene modifiers, a new class of drugs, have become
      commercially available as a promising medication for asthma. According to the
      1997 National Institutes of Health guidelines, the leukotriene modifiers are
      indicated in mild persistent asthma as an alternative to inhaled steroids.
      Nonetheless, they have been used in patients with moderate and severe asthma and,
      in some cases, they have made it possible for patients to taper or discontinue
      their use of oral steroids, thereby controlling their asthma while avoiding the
      side effects of oral corticosteroids. Since the introduction of zafirlukast,
      there have been reported at least eight cases of Churg-Strauss syndrome, a
      granulomatous, necrotizing vasculitis with eosinophilia, associated with the use
      of zafirlukast. No other leukotriene modifier has yet to be associated with the
      syndrome. All the patients in whom Churg-Strauss syndrome developed were patients
      with asthma who were taking zafirlukast and were being weaned from oral
      corticosteroids. Reported here is a case of Churg-Strauss syndrome in a patient
      referred to the authors. Included is a review of the literature of the
      association of Churg-Strauss syndrome and zafirlukast therapy.

PMID- 9615560
TI  - The sword and the scalpel--the osteopathic 'war' to enter the Military Medical
      Corps: 1916-1966.
AB  - This article examines the 50-year struggle of osteopathic physicians to gain
      entry into the US Military Medical Corps on the same basis as allopathic
      physicians. The author explores various arguments put forth by both physician
      groups, as well as those arguments presented by the respective surgeons general
      and relevant government officials.

PMID- 9615561
TI  - Physical restraints in nursing homes: a review of the literature since the
      Nursing Home Reform Act of 1987.
AB  - The use of physical restraints is one of the most negative features of nursing
      home care. Their use significantly affects the quality of life of residents. In
      an attempt to limit the use of restraints, the Nursing Home Reform Act (NHRA) of
      1987 contained provisions regulating their use. In this article, the authors
      review the literature on the use and consequences of physical restraints in
      nursing homes since the passage of the NHRA. First, they describe the history
      behind the use of restraints and define what is considered to be a physical
      restraint. Second, they examine the four most common justifications for restraint
      use. Third, they describe the incidence and prevalence of restraint use. Fourth,
      they address demographic and clinical characteristics of residents that have been
      found to be associated with restraint use. Fifth, they examine negative outcomes
      of restraining residents. Finally, they describe alternatives to using
      restraints.

PMID- 9615562
TI  - Monitoring the consequences of uninsurance: a review of methodologies.
AB  - The proportion of the United States population without health insurance continues
      to grow. How will this affect the health of the nation? Prior research suggests
      that the uninsured are at risk for poor health outcomes. They use fewer medical
      services and have higher mortality rates than do insured persons. The episodic
      nature of uninsurance and its prevalence among disadvantaged groups makes it
      difficult to ascertain the health effects of uninsurance. The goal of this review
      is to assist researchers and policy makers in choosing methodologies to assess
      the effects of uninsurance. It provides a compendium of methods that have been
      used to examine the health consequences of uninsurance, the populations in which
      these methods have been used, and the strengths and weaknesses of different
      approaches. The review highlights the need for more longitudinal studies that
      focus on community-based samples of the uninsured.

PMID- 9615563
TI  - Medicaid enrollment choice into managed care health plans.
AB  - Rural Aid to Families with Dependent Children (AFDC) Medicaid recipients were
      surveyed to identify factors that influenced their enrollment choice between two
      managed care health plans and the traditional Medicaid free-for-service plan.
      Bivariate and logistic regression analyses provided evidence that the Medicaid
      institutional information structure directly influenced recipient decision to
      enroll in managed care plans. Current smokers were more likely to choose a
      managed care plan in this sample. There was no evidence that health status,
      health service use patterns, marital status, or ethnicity was related to the
      enrollment decision. Of those who chose the traditional Medicaid fee-for-service
      plan, 41 percent reported that they did not understand what managed care was.

PMID- 9615564
TI  - Availability of cardiac technology: trends in procedure use and outcomes for
      patients with acute myocardial infarction.
AB  - This study examines temporal trends in the use and outcomes of cardiac procedures
      for patients hospitalized with acute myocardial infarction in Department of
      Veterans Affairs (VA) hospitals with and without invasive cardiac services.
      Between 1988 and 1994, there was striking overall growth in the use of cardiac
      procedures in the VA. Over this time period, the authors found persistent
      variation in the use of cardiac procedures but diminished differences in patient
      survival among patients admitted to different types of hospitals. Growth of
      cardiac procedure use and improvements in patient survival were most significant
      in hospitals without on-site invasive cardiac services. We were unable to
      determine whether survival gains were associated with increased procedure use or
      unmeasured improvements in the process of care. These trends raise intriguing
      questions about access to and outcomes of cardiac procedures in health systems
      composed of hospitals with and without a full complement of on-site invasive
      cardiac services.

PMID- 9615565
TI  - Human fertility and differential birth rates in American eugenics and genetics: a
      brief history.
AB  - Eugenics is a broad term used to describe a variety of social and state-sponsored
      reform movements. Although we usually think of Nazi atrocities when we hear the
      word "eugenics," in this article I discuss the manifestations of hereditary
      reform worldwide. In particular, I consider the history of eugenics in America,
      focusing on concerns about the differences in birth rates between various racial,
      ethnic, and educational groups. In the early twentieth century, the social and
      cultural expectations that surrounded the growing knowledge in genetics implied
      an ethical imperative for physicians. Physicians were expected to use their
      knowledge about genetics to help them decide what sort of advice and assistance
      should be given to those who wanted knowledge about birth control, or help in
      resolving problems concerning sterility and infertility. Today, with growing
      knowledge about human genetics, physicians are subject to increasing pressure to
      make similar judgments.

PMID- 9615566
TI  - The changing moral landscape of human reproduction: two moments in the history of
      in vitro fertilization.
AB  - Ethical attitudes toward in vitro fertilization (IVF) have varied historically.
      This paper discusses the changes in views about the morality of human IVF by
      exploring the response to a pair of critical moments in the history of this
      reproductive technology: the announcement of the first successful IVF experiment
      by John Rock and Miriam Menkin in 1944 and the first successful IVF live birth of
      Louise Brown in 1978. By exploring public and private reactions to these two
      events in the context of wider social and political developments, this paper
      demonstrates the degree to which our notions of the morality of medical
      experimentation and of reproductive technologies are socially constructed and
      historically contingent.

PMID- 9615567
TI  - Reproductive genetics and today's patient options: prenatal diagnosis.
AB  - Rapid and safe prenatal diagnosis has become the standard of care in high-risk
      pregnancy. The safety and reliability of prenatal diagnosis by mid-trimester
      amniocentesis and first-trimester chorionic villus sampling (CVS) are reviewed,
      and accepted medical indications for referral are defined for both procedures.
      Techniques for evaluating the fetus for abnormality including amniocentesis, CVS,
      ultrasound, percutaneous umbilical blood sampling, fetal biopsy, amniotic fluid
      alpha-fetoprotein analysis, and maternal serum screening are described. The need
      for appropriate prenatal genetic counseling before any diagnostic modality is
      emphasized.

PMID- 9615568
TI  - Equivocal notions of accuracy and genetic screening of the general population.
AB  - The explosive growth in genetic technology quickly will make possible an
      unprecedented number of tests for genetically based conditions. A necessary
      condition for the use of such tests without risk of harm to the patient is their
      accuracy. However, most discussions of test accuracy in the literature have
      equivocated between two importantly different meanings of the word. In
      particular, it must be remembered that a high analytic accuracy does not imply a
      high diagnostic accuracy. Questions about the diagnostic accuracy of genetic
      tests presently loom large because of our limited knowledge of the complex
      etiology of disease and the distribution within the general population of the
      causal factors involved. Our current inability to supply patients with accurate
      diagnosis based on genetic information, however, is less problematic when
      examined in the context of new reproductive technologies such as in vitro
      fertilization and intraplasmic sperm injection.

PMID- 9615569
TI  - Ethical issues involving multifetal pregnancies.
AB  - Selective termination is a procedure in which an anomalous fetus in a multifetal
      pregnancy is terminated with the intent of allowing the pregnancy to continue, so
      that the patient delivers one or more healthy infants at term. Multifetal
      pregnancy reduction is the elective reduction of three or more fetuses to a
      smaller number in an attempt to reduce the incidence of premature delivery in
      these patients. The ethical issues relating to these two procedures are quite
      different. Data are presented relating to the efficacy and safety of each
      procedure, and the ethical issues relating to them are discussed.

PMID- 9615570
TI  - Reproductive choice and public policy: a doctor's perspective.

PMID- 9615571
TI  - The end of motherhood as we have known it.
AB  - The new reproductive technologies have dramatic social implications, undermining
      previous biological assumptions about the relationships between mothers and
      fathers and children within families. Insofar as we may now distinguish between
      genetic motherhood, gestational motherhood, and social motherhood, three
      different women may participate in the decision to produce a child. Who is its
      "real" mother? Given the complicated interpenetration of nature and technology
      within reproductive situations today, we need to develop new social accounts of
      what it means to create a family. We require new narratives that highlight the
      wondrous kinship possibilities afforded by the new reproductive technologies
      while at the same time articulating the responsibilities of parenthood within new
      familial groupings.

PMID- 9615572
TI  - Ideology and technology: the social context of procreative technology.
AB  - Biomedical practices and research in procreation are shaped by three ideologies
      deeply rooted in American society: patriarchy with its control of women's bodies
      in the interest of men's procreative concerns and with its focus on 'seeds' and
      therefore genetics; technology as an ideology of efficiency, productivity,
      rationality, and control; and capitalism both as an ideology and as a practice, a
      mechanism that markets technologies of procreation.

PMID- 9615573
TI  - Issues in medical ethics: 1997. Cases and doubts.

PMID- 9615574
TI  - How perfect? A case of prenatal diagnosis.

PMID- 9615576
TI  - [Health centers and family physician].

PMID- 9615575
TI  - Elmer's glue, Elsie and you: clinical applications of adhesion molecules.
AB  - An effective response to injury or inflammation requires leukocyte migration from
      the endovascular compartment into areas of inflammation. This process requires
      the appropriate expression of adhesion molecules, which mediate cell-cell and
      cell-extracellular matrix interactions. A better understanding of the roles of
      adhesion molecules in normal and pathological conditions might lead to the
      development of more effective therapeutic interventions. Features of several
      classes of adhesion molecules, including immunoglobulin superfamily, selectins,
      and integrins, are reviewed along with how they participate in leukocyte
      endothelial interactions. The role of cell adhesion molecules in a variety of
      pathological conditions, including graft rejection, reperfusion injury, and acute
      lung injury are discussed. In addition, some recent studies that explore
      therapeutic uses of adhesion molecules are summarized.

PMID- 9615577
TI  - [Is it beneficial to search the causes of asthma?].

PMID- 9615578
TI  - [Syndromes--correct diagnosis means better follow-up].

PMID- 9615579
TI  - [Helicobacter pylori--do we know what we are doing?].

PMID- 9615580
TI  - [Immunoglobulin E, viral antibodies and obstructive lung disease in adults. The
      relation between antibody level in serum, lung function and non-specific
      bronchial reactivity].
AB  - We have measured immunoglobulin E levels and respiratory virus antibodies and
      examined their possible role as risk factors for obstructive lung disease in
      adults. We observed that increased total serum IgE levels were associated with
      reduced lung function in subjects with obstructive lung disease, but not in
      asymptomatic subjects. Subjects sensitised to indoor allergens (house dust mites,
      cats and mould) had reduced lung function and increased, non-specific, bronchial
      responsiveness compared with individuals who were not sensitised to indoor
      allergens. Similar relationships were not observed for subjects sensitised to
      outdoor allergens (birch and timothy). The presence of respiratory virus
      antibodies was vaguely associated with reduced lung function, but was not related
      to increased, non-specific, bronchial responsiveness. In adults in this community
      sensitisation to indoor allergens is a strong predictor of reduced lung function
      and increased, non-specific, bronchial responsiveness, which are again closely
      associated with obstructive lung disease.

PMID- 9615581
TI  - [Cadaver organ donation in Norway 1993-96].
AB  - The annual number of cadaveric organ donors increased from 13.1 per million
      inhabitants in the period 1989-92 to 15.8 in the period 1993-96. Multiple organ
      harvesting was performed in 68% of the donors. There are significant differences
      in donation rate between health regions. An increase to 20 organ donors per year
      per million inhabitants is required to meet the anticipated need for organs.
      Strategies to increase organ donation are discussed.

PMID- 9615582
TI  - [Simpson-Golabi-Behmel syndrome. A new overgrowth syndrome with increased risk of
      tumor development].
AB  - Simpson-Golabi-Behmel's syndrome is characterized by pre- and postnatal
      overgrowth, coarse face, visceromegali, congenital anomalies such as heart
      defects, diaphragmatic hernia and gastrointestinal malformations. Etiology is X
      linked inheritance, the causative gene (GPC3) has recently been discovered.
      Female carriers may have mild symptoms. We report on an eight year old boy with
      characteristic anomalies and moderately retarded psychomotor development.
      Differentiating Simpson-Golabi-Behmel's syndrome and other overgrowth syndromes,
      such as Beckwith-Wiedemann's and Sotos' syndrome can be difficult. Clinical
      overlap and differences between these three conditions are discussed. The
      diagnosis of Simpson-Golabi-Behmel's syndrome is important because of increased
      risk for cardiac arrhytmias and for development of embryonal tumors such as
      neuroblastoma and Wilms' tumor in early childhood.

PMID- 9615583
TI  - [Cecal volvulus as a complication in Cornelia de Lange syndrome. A case report
      and literature review].
AB  - Colonic volvulus in children is a rare, but serious and important differential
      diagnosis in acute abdominal illness. Our patient with Cornelia de Lange's
      syndrome, was admitted with an acute onset of abdominal pain and in a critical
      condition. Explorative laparotomy revealed a caecal volvulus with necrosis of the
      distal ileum, caecum and proximal colon. The syndrome is characterized by typical
      facial expression, both growth and mental retardation, and various
      gastrointestinal and cardiac anomalies. Predisposing factors contributing to
      volvulus in this syndrome are mental retardation and a higher incidence of
      malrotation and nonfixation of the caecum and ascending colon. The parents of
      children with Cornelia de Lange's syndrome should therefore be counselled so that
      they are able to provide essential information in the event of their children
      experiencing acute illness.

PMID- 9615584
TI  - [47,XYY syndrome. Is diagnosis of significance?].
AB  - Over a 10-year period, from 1984-1995, in the Norwegian county of Vest-Agder,
      five patients in a paediatric clinic were diagnosed as having chromosome
      constitution 47,XYY. There are 1,250 males born a year in Vest-Agder. The
      patients were identified with bias, and not in a routine or prospective screening
      programme. All patients except one, a child who was diagnosed by chance at the
      age of one week; were admitted because of moderate conduct disorders or problems
      at school and striking tallness of stature. The half-brother of one of the 47,XYY
      boys had Klinefelter's syndrome 47,XYY. We conclude that identification of 47,XYY
      syndrome and information about it were of significance and help in counselling
      the patients and their families.

PMID- 9615586
TI  - [Attention deficit/hyperactivity (AD/HD)--development of terminology].
AB  - The aim of the present study is to discuss the terminology pertaining to children
      and adolescents who have been described as disruptive, hyperactive, inattentive,
      and impulsive. Review of the literature covering this century reveals that the
      condition has been given numerous names, which have later been rejected.
      Initially the focus was on brain damage as the cause, but the foundation for this
      explanation gradually failed: the concept was discarded in the 1960s and was
      replaced by the interchangable terms hyperactivity disorder and minimal brain
      dysfunction. The latter was only a few years later replaced by attention deficit
      disorder in the US and hyperkinetic disorder everywhere else. Differences and
      similarities between diagnostic systems and their significance for diagnostic
      practice are discussed. Diagnosis should be based on interdisciplinary work and
      the use of standardized rating scales.

PMID- 9615585
TI  - [Children with Asperger syndrome].
AB  - In 1994 Hans Asperger (1906-80), an Austrian physician, described a group of
      children with impaired social interaction and communication abilities. The name
      of this disorder today is Asperger's syndrome, and it is currently defined under
      the category of pervasive developmental disorder in DSM-IV and ICD-10. In this
      article the following aspects of Asperger's syndrome are focused on: personality,
      epidemiology, etiology, examination, differential diagnosis, management and
      prognosis. The article is based on a literature study. Asperger's syndrome seems
      to be considerably more common than "classic" autism. The syndrome is much more
      common in boys than in girls. The clinical characteristics of Asperger's syndrome
      are probably influenced by many factors, including organic and genetic factors.
      Asperger's syndrome is the term applied to the highest functioning end of the
      autism scale. There are several commonalities between Asperger's syndrome and
      autism, namely impairment of social interaction and communication abilities, and
      range of interests and activities. Differences exist primarily in the degree of
      impairment in language and cognitive development. Differential diagnosis,
      examination and management are discussed. There is a need for further research.
      It is important that the diagnostic criteria for Asperger's syndrome are as
      uniform as possible, and that they do not overlap with infantile autism.

PMID- 9615587
TI  - [Attitude to genetic screening for familial hypercholesterolemia].
AB  - Familial hypercholesterolemia causes premature cardiovascular disease. Genetic
      screening of patients' relatives who have already been diagnosed has proved to be
      more efficient than screening in a general population. Privacy laws in Norway
      forbid physicians to directly contact persons with genetic disorders who are not
      their own patients. We examined attitudes towards this type of screening in a
      representative sample of the Norwegian population and a group of patients with
      familial hypercholesterolaemia. In both groups the majority showed a positive
      attitude towards physicians contacting relatives directly to detect individuals
      with familial hypercholesterolaemia. In both groups the majority wanted to know
      whether, based on the diagnosis of relatives, they might also be affected. Both
      groups wanted this information regardless of the risk of their being affected. We
      conclude that the privacy laws should be amended to conform with the attitudes of
      the population and the patients, thus enabling physicians to contact relatives
      directly.

PMID- 9615588
TI  - [Does synthetic filling in pillows and comforters increase the risk of severe
      asthma?].

PMID- 9615589
TI  - [What did women eat during the Stone Age and what do they eat today? Iron in food
      then and now].

PMID- 9615590
TI  - [Iron--friend or enemy? New scientific results about iron balance in boys during
      puberty].

PMID- 9615591
TI  - [Assessment of the concept DAMP--deficit in attention, motor control and
      perception].

PMID- 9615592
TI  - [Hyperkinetic disorders--AD/HD, MBD/DAMP--how are we supposed to name it?].

PMID- 9615593
TI  - [Treatment with homologous feces].

PMID- 9615594
TI  - [Risky treatment without effect?].

PMID- 9615595
TI  - [Alternative therapy and cancer].

PMID- 9615596
TI  - [Ethics and the student].

PMID- 9615597
TI  - Flying in the face of known fact.

PMID- 9615598
TI  - Communication of sexual risk behavior among late adolescents.
AB  - A grounded theory approach was used to describe how males and females in late
      adolescence communicate with their sexual partners about sexual risk behaviors.
      Interviews were audiotaped with 18 women and 15 men from a university in the
      southeastern United States. Verbatim transcripts were analyzed using constant
      comparative analysis. Building trust was identified as the core variable for both
      men and women. For women, prerequisites for building trust were being involved in
      caring relationships and indirectly gathering information about potential sexual
      partners. For men, prerequisites were being involved in caring relationships and
      using their instincts. Women usually initiated safe-sex talk, but men were
      willing to discuss it, once the conversation was initiated. Findings can serve as
      a guide for developing nursing strategies that promote more effective
      communication about sexual risk behavior in this age group.

PMID- 9615599
TI  - An analysis of elderly clients' views of mobility.
AB  - This article presents findings from part of a larger qualitative study designed
      to explore the concept of mobility within the context of concept development.
      Primary nurses and their elderly clients made up the two study samples. Data were
      collected through semistructured interviews and analyzed using thematic content
      analysis techniques. In this article, only data from the client sample are
      reported. Findings suggested that the elderly clients defined mobility in terms
      of three interrelated dimensions: physical, cognitive, and social. From client
      descriptions of mobility, six qualities emerged: ease and freedom of movement,
      independence, automaticity, purposefulness, self-environmental awareness, and
      continuity.

PMID- 9615600
TI  - A study of introspectiveness in adolescents and young adults.
AB  - The purpose of this study was to examine the relationship between
      introspectiveness and the theoretically related variables of close friend
      solidarity, self-esteem, and symptom patterns in early, middle, and late
      adolescents, as well as in young adults. Samples of early (n = 103), middle (n =
      107), and late adolescents (n = 101) as well as young adults (n = 70) completed
      the Introspectiveness Scale, the Close Friend Solidarity Instrument, the
      Rosenberg Self-Esteem Scale, and the Symptom Pattern Scale in classroom settings.
      Hypotheses were tested using Pearson correlations, with a one-tailed test of
      significance. Introspectiveness was statistically, significantly, and positively
      related to close friend solidarity in all adolescents but not in young adults;
      introspectiveness was statistically, significantly, and inversely related to self
      esteem in all adolescents but not in young adults. Finally, introspectiveness was
      statistically, significantly, and positively related to symptom patterns in all
      adolescents and in young adults.

PMID- 9615601
TI  - The oldest old, ADL, social network, and loneliness.
AB  - This study examined the influence of activities of daily living (ADL) and
      frequency of social contacts on the loneliness and social relationships in a
      sample of very elderly individuals. Associations between functional ability,
      social contacts, and emotional loneliness and social loneliness were also
      assessed. The sample was composed of 221 participants, age 80 to 105 years,
      residing in the greater Bergen area in Norway. Results demonstrated that
      dependence on the environment in ADL is related to low levels of emotional
      loneliness, whereas only dependence in activities of toileting and transferring
      corresponded with low levels of social loneliness. High frequency of social
      contacts with family, friends, or neighbors was negatively related to both
      emotional and social loneliness. Results show that frequency of such contacts
      appeared to buffer the effect of continence on emotional loneliness and the
      effect of toileting and transferring on social loneliness.

PMID- 9615602
TI  - Model selection for covariance structures analysis in nursing research.
AB  - Covariance structures analysis is often used in nursing research to appraise
      statistical models reflecting complex human health processes. The model selection
      approach in covariance structures analysis is designed to select the "best" model
      from a specified set of theoretically defensible, competing alternatives, all of
      which are viewed as approximations. Model selection criteria explicitly
      incorporate both model misfit in the population and sampling error to evaluate
      the set of models. The result is that interpretability of model parameters and
      goodness-of-fit are enhanced simultaneously. Relative merits of the model
      selection approach are identified in light of technical concerns, parsimony, and
      use of scientific theory in nursing.

PMID- 9615603
TI  - Nurses' perceptions of people who are homeless.
AB  - There are few data-based reports about the perceptions of nurses toward
      marginalized groups and even fewer about the transformation of perceptions. The
      purpose of this study was to explore nurses' perceptions of people who are
      homeless and to describe transforming experiences. Rich, detailed experiences of
      the care provided to people who were homeless were elicited through in-depth
      interviews with 15 nurses and nursing students. Without exception, each
      participant in this study indicated that listening, connecting, and understanding
      were important to them in changing previously held negative beliefs. However,
      when clients did not express appreciation or behave in expected ways, nurses
      became frustrated and voiced negative feelings about people who are homeless.
      Study findings emphasize the importance of listening and connecting with people
      who are different from ourselves so that our shared humanity is acknowledged and
      appreciated.

PMID- 9615604
TI  - The exercise of self-care agency scale.
AB  - This study examined the perceptions of the exercise of self-care in nursing
      students in Japan. An instrument to measure exercise of self-care agency
      developed by Kearney and Fleischer was used. The instrument was translated from
      English into Japanese and administered to a convenience sample of 461 students
      who were enrolled in nursing and early childhood education for the purpose of
      comparison. Psychometric properties of the Japanese version of the instrument
      were satisfactory. The results from the study were compared with those from
      studies in the United States and Sweden in which the same instrument was
      administered to nursing students. Differences and similarities between these
      studies will shed some light on cross-cultural directives for international
      nursing research on the exercise of self-care agency.

PMID- 9615605
TI  - Balancing ethical quandaries with scientific rigor: Part 1.

PMID- 9615606
TI  - Cardiovascular disease and steroid hormone contraception. Report of a WHO
      Scientific Group.
AB  - Over 90 million women worldwide, including over 44 million in developing
      countries, are now using oral contraceptives. Despite their advantages, there is
      concern about the links between combined oral contraceptives and the risk of
      cardiovascular disease. Although most contraceptive users are healthy with a low
      background incidence of major disease, the very large number of women using oral
      contraceptives throughout the world means that even modest elevations in risk
      have the potential to affect a large number of women. This report presents the
      conclusions of a WHO Scientific Group that met to discuss the association between
      use of steroid hormone contraceptives (including combined oral contraceptives)
      and the risk of cardiovascular disease in women. The Scientific Group evaluated
      the data available from case-control and cohort studies on acute myocardial
      infarction, ischaemic and haemorrhagic stroke, and venous thromboembolism. The
      Group also reviewed the data on possible biological mechanisms for the effects of
      combined oral contraceptives on cardiovascular disease, including the interplay
      between lipoprotein metabolism, humoral regulators such as insulin, coagulation
      and fibrinolysis, the products of the endothelium of blood vessels and the renin
      angiotensin-aldosterone system. The Group identified factors which may predict,
      for individual women, an increased risk of cardiovascular effects with use of
      different hormonal contraceptives, and assessed whether the various compositions
      of combined oral contraceptives have different risk profiles for cardiovascular
      disease. The report presents the Group's conclusions relating to the various
      types of cardiovascular disease in women of reproductive age, together with a
      list of recommendations for further research.

PMID- 9615608
TI  - WHO Expert Committee on Biological Standardization. Forty-sixth Report.
AB  - This report presents the recommendations of a WHO Expert Committee commissioned
      to coordinate activities leading to the adoption of international requirements
      for the production and control of vaccines and other biologicals and the
      establishment of international biological reference materials. The report starts
      with a discussion of general issues brought to the Committee's attention and
      provides information on the status and development of reference materials for
      various antibiotics, antibodies, antigens, blood products, cytokines,
      endocrinological and related substances and toxins. The second part of the
      report, of particular relevance to manufacturers and national control
      authorities, contains the revised list of laboratories approved by WHO for the
      production of yellow fever vaccine, revised requirements for yellow fever
      vaccine, an amendment to the General Requirements for the Sterility of Biological
      Substances, and a summary protocol for the batch release of virus vaccines.

PMID- 9615607
TI  - WHO Expert Committee on Drug Dependence. Thirtieth report.
AB  - The scale of drug dependence has grown dramatically in the past quarter-century.
      Preventing dependence and reducing the harm associated with the use of
      psychoactive substances is a challenge for health services and governments the
      world over. This report of a WHO Expert Committee categorizes the different types
      of harm that can result from psychoactive substances, whether illicit or legally
      available, and describes the steps that can be taken to treat health problems and
      stop them from occurring. The report looks at the cost and effectiveness of
      various treatment methods, drawing on evidence from research findings, and gives
      a detailed outline of the elements needed for an effective national treatment
      system. It addresses the question of whether dependent persons should be given a
      "controlled supply" of drugs and proposes for further review several substances
      that have potential for abuse. The Expert Committee's recommendations cover drug
      policies and treatment services, as well as training, information needs and
      research. The report lays the foundation for realistic but sound strategies in
      national and international efforts to reduce the health damage caused by the use
      of psychoactive substances.

PMID- 9615609
TI  - Pilot-scale extraction of PHB from recombinant E. coli by homogenization and
      centrifugation.
AB  - A new method of poly-beta-hydroxybutyrate (PHB) extraction from recombinant E.
      coli is proposed, using homogenization and centrifugation coupled with sodium
      hypochlorite treatment. The size of PHB granules and cell debris in homogenates
      was characterised as a function of the number of homogenization passes.
      Simulation was used to develop the PHB and cell debris fractionation system,
      enabling numerical examination of the effects of repeated homogenization and
      centrifuge-feedrate variation. The simulation provided a good prediction of
      experimental performance. Sodium hypochlorite treatment was necessary to optimise
      PHB fractionation. A PHB recovery of 80% at a purity of 96.5% was obtained with
      the final optimised process. Protein and DNA contained in the resultant product
      were negligible. The developed process holds promise for significantly reducing
      the recovery cost associated with PHB manufacture.

PMID- 9615610
TI  - A study on the effect of operating parameters on the cross-flow microfiltration
      of yeasts.
AB  - The effects of pump speed, cumulative permeate volume and concentration of feed
      (yeast cells) on the permeate flux have been studied on a batch cross-flow
      microfiltration process. The experiments were conducted for two different
      cellulose acetate membrane modules of 0.2 micron and 0.45 micron pore size. A
      three factor experiment was designed for this purpose and the effect of the
      operating parameters on the filtration rate was studied by the analysis of
      variance (ANOVA). It is concluded from the analysis of the experimental data that
      pump speed has the maximum bearing upon the permeate rate within the operating
      range of parameters. Fouling conditions were examined in the light of colloids
      deposition on membranes due to surface interactions. However this paper looks
      into the relationship and sensitivity of the operating parameters in a cross-flow
      microfiltration unit rather than exploring the theoretical principles behind the
      observed phenomena.

PMID- 9615611
TI  - The application of aqueous two-phase systems to the purification of
      pharmaceutical proteins from transgenic sheep milk.
AB  - Transgenic sheep milk containing the protein human alpha 1-Antitrypsin (AAT) was
      partitioned in Poly(ethylene glycol) (PEG)-Sulphate and PEG-Phosphate biphasic
      systems. Individual partition coefficients for AAT and some of the milk proteins
      were determined in these systems. The effects of PEG molecular weight, pH and the
      inclusion of NaCl on the partitioning of the proteins were also studied. It was
      found that increasing the concentration of NaCl and decreasing the molecular
      weight of the PEG resulted in an increase of the partition coefficients of the
      proteins to the upper (PEG) phase. This partitioning effect was greater for the
      more hydrophobic proteins and particularly in systems having a pH close to the
      isoelectric point of the protein. Solubilities of the proteins in increasing
      concentrations of ammonium sulphate were measured in order to investigate the
      effects of hydrophobic and electrostatic interactions on the partitioning of
      these proteins in aqueous two-phase systems. Those proteins that precipitated at
      low levels of ammonium sulphate showed an increase in partition coefficient at
      low concentrations of NaCl, or they were precipitated at the interface of the
      phase at low concentrations of NaCl. Proteins that had low salting out constants
      in ammonium sulphate solutions were relatively unaffected by NaCl in ATPS. It is
      probable however that conformational changes and the state of aggregation of
      proteins are also important and should be invoked in describing the partitioning
      behavior observed for beta-Lg for example. Comparison of theoretical and
      experimental values for AAT yield and purity showed clearly that partition
      coefficients are influenced by the degree of purity and values obtained with
      purified standards are not necessarily the same as for the same protein present
      in a complex mixture. Under the most favourable conditions using a 4% w/w loading
      of transgenic ovine milk, we obtained a 91% yield of AAT in the PEG phase with a
      purity of 73%.

PMID- 9615612
TI  - An efficient and optimized purification procedure for the superoxide dismutase
      from Aspergillus niger. Partial characterization of the purified enzyme.
AB  - Cu,Zn-superoxide dismutase was isolated from Aspergillus niger mycelia, harvested
      at the mid-logarithmic growth phase. The purification scheme aimed at the
      optimization of the ethanol/chloroform extraction (Tsuchihashi extraction)
      through response surface methodology. Upon optimum extraction conditions, it was
      possible to obtain electrophoretically pure enzyme preparations, by the
      application of one step anion exchange chromatography. The enzyme yield of this
      simple purification procedure was above 75% while the specific activity of the
      final preparation was among the highest reported for eucariotic microorganisms.
      The purified enzyme exhibited similar physicochemical characteristics with other
      Aspergillus sp. superoxide dismutases revealing an apparent tetrameric structure
      with a subunit molecular weight of 19 kDa, and a pl of 5.95.

PMID- 9615613
TI  - Characteristics of the adsorption of immunoglobulin M onto Q Sepharose Fast Flow
      ion-exchangers.
AB  - Measurement of adsorption breakthrough curves in packed beds has shown that the
      amounts and rates of uptake of immunoglobulin M (IgM) onto the commonly used
      anionic ion-exchanger Q Sepharose Fast Flow (based on 6% agarose) are severely
      limited as a result of the large molecular size of this adsorbate (RMM 950,000).
      A similar ion-exchanger based on a more porous 4% agarose, Q Sepharose 4 Fast
      Flow was evaluated as an alternative adsorbent for the purification of IgM.
      Equilibrium adsorption isotherms and the effective diffusivities of IgM within
      these two adsorbents were measured. Q-Sepharose 4 Fast Flow was found to have a
      maximum capacity for IgM 2.5 times greater than that of Q Sepharose 6 Fast Flow
      and the effective diffusivity of IgM was found to be between 6 and 7 times
      greater than with the latter material. Comparison of the breakthrough curves
      obtained for these adsorbents at a variety of flow velocities confirm that Q
      Sepharose 4 Fast Flow is a superior adsorbent for the capture and purification of
      large proteins.

PMID- 9615614
TI  - The effect of n-butanol on Triton X-114 phase partitioning.
AB  - n-Butanol interferes with the fractionation of amphiphilic and hydrophilic
      molecules during the Triton X-114 phase separation procedure. The indicators oil
      red (hydrophobic) and p-nitrophenol (hydrophilic) were useful for predicting the
      effectiveness of the Triton X-114 partition method. For n-butanol extracts
      containing oil red, 5'-nucleotidase, or alkaline phosphatase, the hydrophobic
      molecules and Triton X-114 were retained in the aqueous phase during incubations
      at 30 degrees C. The n-butanol interference was concentration-dependent and was
      reduced by lowering the final n-butanol concentration of the sample to 1.5% (v/v)
      or less. The results demonstrate how buffer-diluted n-butanol extracts of 5'
      nucleotidase and alkaline phosphatase can be successfully employed for subsequent
      Triton X-114 fractionation of the enzymes.

PMID- 9615615
TI  - Compositional changes in glycoconjugates recognized histochemically with lectins
      in Purkinje cells in suckling and adult rats.
AB  - Cerebella from suckling and adult rats were examined histochemically with 19
      different biotin-labeled lectins. Purkinje cells from postnatal rats had a marked
      ability to combine with many lectins, but minimal ability was found in adult rats
      except for Con-A, LEL, and MAL lectins. The cell body of Purkinje cells on
      postnatal day 7 was strongly labeled with 6 lectins (Con-A, LTL, MAL, SJA, UEA-I,
      and VVA). Only moderate staining was observed with these lectins on postnatal day
      5. The dendritic tree of the cells showed a moderate labeling ability with LTL
      and UEA-I on postnatal days 15 and 20. The dendritic tree was strongly labeled
      with MAL on postnatal days 10, 15, 20 and adult. Positive reactions were observed
      in the cells when cerebellar sections from rats on postnatal day 7 were incubated
      with 3 other lectins (AAL, LEL, and SBA). The cells on postnatal day 7 were
      rarely labeled with BSL-II, DBA, DSL, LCA, PNA, PSA, RCA120, SSA, STL, and WGA.
      Purkinje cells on postnatal day 7 may be rich in N-linked oligosaccharides, with
      terminal sugar structures that resemble blood-group-related antigens (type H)
      and/or tumor-related antigens. These glycoconjugates may be present at low levels
      in the Purkinje cells of adult rats. Dendrites of Purkinje cells of adult rats
      were strongly labeled by Con-A, LEL, and MAL. The dendrites of Purkinje cells may
      be rich in highly branched oligosaccharides.

PMID- 9615616
TI  - Relationships of salinity tolerance to immunolocalization of Na+,K(+)-ATPase in
      the gill epithelium during seawater and freshwater adaptation of the guppy,
      Poecilia reticulata.
AB  - The relationships of salinity tolerance to immunolocalization of Na+,K(+)-ATPase
      in the gill epithelium were examined during seawater and freshwater adaptation of
      the guppy. In fresh water, immunoreactivity for Na+,K(+)-ATPase appeared in two
      types of chloride cells, which are located on the primary lamellae of the gills.
      Immunoreactivity was strong in the chloride cells located at the base of the
      secondary lamellae and weak in the chloride cells located at the interlamellar
      region. During seawater adaptation, the strongly-immunoreactive chloride-cells
      increased in number and size while the weakly-immunoreactive chloride-cells
      decreased in number with an increase in salinity tolerance. In the fish of the
      seawater-adapted strain, on the other hand, most of the chloride cells were
      located at the base of the secondary lamellae and showed strong immunoreactivity.
      During freshwater adaptation, the strongly-immunoreactive chloride-cells
      decreased in number and size while the weakly-immunoreactive chloride-cells
      increased in number with a decrease in salinity tolerance. A positive correlation
      was observed between the salinity tolerance and the occupying area of the
      strongly-immunoreactive chloride-cells while a negative correlation was observed
      between the salinity tolerance and the occupying area of the weakly
      immunoreactive chloride-cells during the seawater and freshwater adaptation.
      These results directly suggested that not only the occupying area of chloride
      cells but also the expression of Na+,K(+)-ATPase protein in the cells is
      important with respect to the osmoregulatory function in the gills and
      hypoosmoregulatory ability at the individual level.

PMID- 9615617
TI  - Irreversible potent activation and reversible inhibition of trypsin-like activity
      of 20S proteasome purified from Xenopus oocytes by fatty acid.
AB  - The 20S proteasome purified from animal cells has various latent peptidase
      activities. Fatty acids such as linoleic, linolenic and oleic acids strongly
      activate both the chymotrypsin-type and peptidylglutamylpeptide (PGP) hydrolase
      type activities, but have been reported to have little activation or inhibition
      of the trypsin-type activity. We show here that an increase of the fatty acid
      concentration produces activation of chymotrypsin-type and PGP hydrolase-type in
      a biphasic fashion: no effect until the threshold concentration and then a sharp
      activation. In contrast, the trypsin-type activity was markedly inhibited at low
      concentrations of fatty acid, slightly activated at higher concentrations, and
      inhibited again at even higher concentrations. The inhibition was removed when
      the concentration of fatty acid was reduced by dilution after pre-incubation with
      the fatty acid. As a result, the activation pattern became biphasic, which was
      identical to that of chymotrypsin-type and PGP hydrolase-type activities. These
      results suggest that in the chymotrypsin-type and PGP hydrolase-type peptidase
      fatty acids bind first to a class of sites without direct effect on the peptidase
      activity, but after saturation of this class it permits more fatty acid to bind
      to another class of sites involved in the activation. In the trypsin-type
      peptidase an additional class of fatty acid binding sites is uniquely present,
      which is involved in the enzyme inhibition. The dilution procedure described
      above removes the fatty acid molecules bound to the inhibition sites, but not the
      fatty acid molecules bound to the activation sites; this results in the fatty
      acid activation profile indistinguishable from that of the chymotrypsin- and PGP
      hydrolase-type peptidases.

PMID- 9615618
TI  - Hoxd-4 expression during pharyngeal arch development in flounder (Paralichthys
      olivaceus) embryos and effects of retinoic acid on expression.
AB  - Teleost fish develop seven pharyngeal arches (mandible, hyoid and five gill
      arches) which give rise to the jaw and gills, and skeletal cell populations which
      originate from the cranial neural crest. The anterior border of expression of the
      Deformed (Dfd) group is located in the hindbrain and pharyngeal region. To
      investigate pharyngeal skeletal formation in the teleost fish, we cloned the cDNA
      coding Hoxd-4 from a cDNA library for flounder (Paralichthys olivaceus) embryos,
      and analyzed gene expression pattern during embryogenesis and the effects of
      retinoic acid (RA) on this gene expression. Between the 21-somite and prim-5
      stages, Hoxd-4 was expressed in the central nervous system from rhombomere 7 to
      the spinal cord, and in the pharyngeal region posterior from gill arch 2. Its
      expression then became restricted to cartilage precursor cells of gill arches 2
      5. When embryos in the early shield stage were exposed to RA at concentrations
      above 10(-7) M, the anterior border of Hoxd-4 expression shifted anteriorly in a
      dose-dependent manner, both in the central nervous system and pharyngeal region.
      We propose that, during gill skeleton formation, Hoxd-4 functions in the
      specification of regional identity between gill arches 1 and 2, and that their
      identity is affected by treatment with RA.

PMID- 9615619
TI  - Developmental roles of nuclear complex factors released during oocyte maturation
      in the ascidians Halocynthia roretzi and Boltenia villosa.
AB  - The developmental roles of factors associated with the nuclear complex of
      Halocynthia roretzi and Boltenia villosa oocytes were investigated by cutting
      mature oocytes into animal and vegetal merogons before and during GVBD. Animal
      and vegetal merogons were cultured in sea water until the GV cytoplasm had
      dispersed within the cytoplasm of control oocytes and then they were cross
      fertilized and scored for their ability to undergo normal development.
      Halocynthia oocyte fragments produced from the animal region of oocytes
      containing intact GVs exhibited a low frequency of polyspermy, a high frequency
      of fertilization and cleavage, and a high frequency of expressing an epidermal
      antigen, Epi-2. In contrast, merogons produced from the vegetal region of
      Halocynthia oocytes in which GVs were intact exhibited a high frequency of
      polyspermy, did not undergo cell division, and expressed a high frequency of Epi
      2 expression. When vegetal fragments were produced after the dispersal of
      approximately 50-70% of the GV nucleoplasm, these merogons exhibited a low
      frequency of polyspermy, high frequencies of cell division (including the
      formation of epidermal layer), and in most cases expressed Epi-2. Vegetal
      Boltenia fragments produced during GVBD in some cases developed into larvae.
      These results suggest that the ascidian GV nucleoplasm may contain factors
      required for fertilization and cell division and that epidermal determinants
      reside in the oocyte cytoplasm.

PMID- 9615620
TI  - Mutual relation between the cell-cycle progression and prespore differentiation
      in Dictyostelium development.
AB  - In Dictyostelium discoideum Ax-2, the cell-cycle progression from the early
      aggregate to mound stage has been proposed to have some connection with prespore
      differentiation. Hereupon, we examined the role of cell-cycle progression during
      the development on cell differentiation, using two kinds of cell-cycle
      inhibitors. Nocodazole, an inhibitor of microtubule formation, was found to
      inhibit greatly cell division around the mound stage as well as during the
      vegetative growth phase, when applied to exponentially growing Ax-2 cells.
      Essentially the same inhibition was attained by treatment of starved Ax-2 cells
      with calyculin A, an inhibitor of serine/threonine protein phosphatases. It is
      noteworthy that the nocodazole- or calyculin A-treated cells exhibit abnormal
      morphogenesis to form a stick-like multicellular structure on non-nutrient agar,
      and also that prespore differentiation as exemplified by the prespore-specific
      Dp87 gene expression and prespore specific vacuole (PSV) formation was greatly
      suppressed. In contrast, the differentiation of prestalk (pstA) cells was
      scarcely affected by the drug treatments. Taken together these results seem to
      indicate that the cell-cycle progression around the mound stage is important for
      prespore differentiation.

PMID- 9615621
TI  - Effects of a soft diet and hypothyroidism on the oxidative capacity of the
      masseter muscle fibers of the young Japanese field vole Microtus montebelli.
AB  - Effects of a soft diet (reduction in mastication activity: an exogenous factor)
      and hypothyroidism (endogenous factors) on the oxidative capacity of the masseter
      muscles in the young Japanese field vole Microtus montebelli, consisting only of
      fast-twitch oxidative (FO) fibers in the adult vole, was investigated
      histochemically and electron microscopically. Oxidative enzyme activity and
      mitochondrial development in the muscle fibers were not affected by a soft diet,
      while they were suppressed by doses of propylthiouracil (PTU) (hypothyroidism).
      Thus, it was suggested that acquisition of the sustained contraction ability in
      the masseter muscles of the young vole is induced by the endogenous factors
      rather than the exogenous factor.

PMID- 9615622
TI  - Changes in circulating LH, sex steroid hormones, thyroid hormones and
      corticosterone in relation to breeding and molting in captive humboldt penguins
      (Spheniscus Humboldti) kept in an outdoor open display.
AB  - Penguins are highly adapted to marine life. Their hydrodynamic efficiency depends
      on feathers which wear with age and need to be replaced regularly. During
      molting, penguins can not enter the sea to forage and are forced to fast.
      Therefore the duration of molting is necessarily brief. To better understand
      molting in penguins, we collected plasma samples from 16 (8 pairs) Humboldt
      penguins kept in an open display pen at Tokyo Sea Life Park from May to
      September, 1994 and estimated circulating concentrations of LH, testosterone,
      estradiol, thyroxine (T4), triiodothyronine (T3) and corticosterone. Body mass
      was also measured at each blood sampling. Throughout the year, reproductive
      activities (egg laying, incubation, hatching and rearing) and molting were
      observed and recorded. Humboldt penguins maintained reproductive activity from
      January to December except during molting. Each pair started molting between the
      end of July and early August; usually males started earlier. The duration of
      molting was 13.4 +/- 0.8 days for males and 12.9 +/- 0.3 days for females. Body
      masses were highest just before the start of molting in both sexes. Plasma
      concentrations of LH were high, (> 2 ng/ml) in May in both sexes, then gradually
      decreased, to 0.53 +/- 0.38 ng/ml in males and 0.72 +/- 0.11 ng/ml in females by
      the end of July. Testosterone and estradiol concentrations in plasma decreased
      and were lowest during molting. On the other hand, plasma concentrations of T4
      were low until early July (ca. 20 ng/ml) and then doubled within 10 days; the
      high levels were maintained for one month and then decreased greatly in males and
      slightly in females. When the plasma concentrations of T4 started to decrease,
      plasma concentrations of LH increased. Changes in plasma T3 were not consistent
      with molting. These results indicate that the decrease of plasma levels of sex
      steroid hormones and the sharp increase of T4 induced molting, which lasted only
      for a short period.

PMID- 9615623
TI  - Changes in cystine aminopeptidase (oxytocinase) activity in mouse serum,
      placenta, uterus and liver during pregnancy or after steroid hormone treatments.
AB  - Changes in cystine aminopeptidase (CAP) activity in serum, placenta, uterus and
      liver in mice under various physiological conditions were examined by enzymatic
      analysis using S-benzyl-L-cysteine-4-methylcoumaryl-7-amide as a substrate.
      Changes in serum CAP activity during pregnancy were less remarkable than those
      reported in humans; the activity was highest at day 13 of pregnancy and lowest at
      day 17. During the estrous cycle, the serum CAP level was high at diestrus, as
      high as that at day 13 of pregnancy. The activity in the male serum was
      significantly low compared to that in the diestrous serum. Although the CAP level
      was especially high in the maternal placenta, levels were also high in the fetal
      placenta, uterus and liver as compared with the serum, suggesting CAP synthesis
      in these tissues. The CAP activity in the uterine tissue was lower in pregnant
      than normal cycling mice. Furthermore, the serum CAP activity was modulated by
      estrogen and progesterone both in females and males, and by androgen in males.
      The relevance of these findings to the physiological role of CAP was discussed.

PMID- 9615625
TI  - Molecular phylogeny of twelve Asian species of epilachnine ladybird beetles
      (Coleoptera, Coccinellidae) with notes on the direction of host shifts.
AB  - We determined the nucleotide sequences of a part of the mitochondrial cytochrome
      c oxidase I gene (1,000 bp) for twelve species of Asian phytophagous ladybird
      beetles belonging to the genus Epilachna, and constructed molecular phylogenetic
      trees for ten "Henosepilachna" species, using two "Epilachna" species as
      outgroups. Based on the suggested phylogenetic trees, we discussed taxonomic
      issues and the direction of host shift in these epilachnines.

PMID- 9615624
TI  - Phylogenetic positions of insectivora in eutheria inferred from mitochondrial
      cytochrome c oxidase subunit II gene.
AB  - For the elucidation of the phylogenetic position of insectivora in eutheria, we
      have sequenced the cytochrome c oxidase subunit II (COII) gene of mitochondria
      for three insectivoran species [musk screw (Suncus murinus), shrew mole
      (Urotrichus talpoides), Japanese mole (Mogera wogura)] and analyzed these amino
      acid sequences with neighbor-joining (NJ) method and maximum likelihood (ML)
      method. NJ analysis shows polyphyly of Insectivora and Chiroptera. Assuming that
      each of Primates, Ferungulata, Chiroptera, Insectivora and Rodentia is a
      monophyletic group, ML analysis suggests that Chiroptera is a sister group of
      Insectivora and that Ferungulata is the closest outgroup to the (Insectivora and
      Chiroptera) clade.

PMID- 9615626
TI  - Employers should take responsibility to ensure that the qualifications of staff.

PMID- 9615627
TI  - Talking in Unison.

PMID- 9615628
TI  - Galloping consumption.

PMID- 9615629
TI  - Who'd be a steward?

PMID- 9615630
TI  - Bitter pills.

PMID- 9615631
TI  - The need to decriminalise cannabis.

PMID- 9615632
TI  - Now nurses are winning recognition for their contribution to patient care.

PMID- 9615633
TI  - The big issue.

PMID- 9615634
TI  - Cut the fat.

PMID- 9615636
TI  - I prescribe, therefore I am.

PMID- 9615635
TI  - Weight on our minds.

PMID- 9615637
TI  - Nursing the nation better.

PMID- 9615638
TI  - Walks on the wild side.

PMID- 9615639
TI  - Clinical care takes centre stage.

PMID- 9615640
TI  - A new look at elderly care.

PMID- 9615641
TI  - Born to nurse. Interview by Adam Legge.

PMID- 9615642
TI  - Nutrition in pregnancy.

PMID- 9615643
TI  - Treating postural hypotension.
AB  - Postural hypotension (PH) is a relatively common condition that particularly
      affects older people. As a symptom it is associated with a variety of conditions
      and may be a transient or long-term feature, depending on the underlying cause.
      This article aims to raise awareness of the condition and give practical advice
      for its treatment.

PMID- 9615644
TI  - Safe handling of patients on cervical traction.

PMID- 9615645
TI  - Different approaches to family therapy.

PMID- 9615646
TI  - Government commitment on pay.

PMID- 9615647
TI  - An awfully big adventure.

PMID- 9615648
TI  - Haunted by bulimia.

PMID- 9615649
TI  - Let's hear it for hip replacements.

PMID- 9615650
TI  - There's a doctor in the house. Interview by Rebecca Coombes.

PMID- 9615651
TI  - Pictures of health.

PMID- 9615652
TI  - The new SENs?

PMID- 9615653
TI  - Talking shop.

PMID- 9615654
TI  - Friend or foe?

PMID- 9615655
TI  - Labour gains.

PMID- 9615656
TI  - Louder than words.

PMID- 9615657
TI  - Soaring success.

PMID- 9615658
TI  - The state of the unions.

PMID- 9615659
TI  - The rights of people with disabilities to have sexual intercourse.

PMID- 9615660
TI  - How do mobile phones affect electromedical devices?
AB  - Mobile telephones and other electronic communication devices can interfere with
      medical equipment when used in close proximity. A study of different devices by
      the Medical Devices Agency showed that emergency services' radio handsets were
      the most likely to cause interference. It recommends that cell telephones be
      switched off in theatres and treatment areas and at a patients' bedsides where
      sensitive medical devices are in use.

PMID- 9615661
TI  - Cholesterol and coronary heart disease: screening and treatment.
AB  - The prevention of coronary heart disease would represent a major saving to the
      NHS. Systematic review of evidence relating to screening for CHD and its
      prevention suggests that blood cholesterol measurement on its own is a poor
      predictor of risk. The evidence suggests that lifestyle changes and drug
      treatments other than cholesterol-lowering drugs are the most cost-effective
      approach to prevention. Nurses should ensure that all risk factors are assessed
      and a range of preventive measures considered in situations where CHD is a
      potential risk.

PMID- 9615662
TI  - Solution-focused brief therapy in primary care.
AB  - Solution-focused brief therapy (SFBT) offers mental health nurses a robust
      framework on which to build appropriate and effective nursing care. This article
      describes efforts to apply ideas derived from this type of therapy in a new nurse
      practitioner post offering a mental health service to patients based in GP
      practices. The approach described develops Brimblecombe's (1995) idea of
      combining a brief therapy approach with nursing care plans in a way ideally
      suited to time-limited mental health nursing in primary care.

PMID- 9615663
TI  - Making the connections to aid mental health.

PMID- 9615664
TI  - Should nurses start running for cover from patients' complaints?

PMID- 9615665
TI  - Promoting continence control.

PMID- 9615666
TI  - Silent suffering.

PMID- 9615667
TI  - American perspectives on continence.

PMID- 9615668
TI  - [Look forward, not backward].

PMID- 9615670
TI  - [A slap in the face of those who need care].

PMID- 9615671
TI  - [Migrants in nursing. Report from the practice of an intercultural social
      service].

PMID- 9615672
TI  - [From Seoul to Koln-Kalk. Experiences of a Korean pediatric nurse in Germany].

PMID- 9615673
TI  - [Culturally sensitive care as an extension of Leininger's nursing theory].

PMID- 9615674
TI  - [Nursing courses seen through a magnifying glass].

PMID- 9615675
TI  - [Practical training].

PMID- 9615676
TI  - [A day in the operating room for nursing students].

PMID- 9615677
TI  - [Locked-in: imprisoned in your own body].

PMID- 9615678
TI  - [Change as chance].

PMID- 9615679
TI  - Bottom line concerns eroding quality health care.

PMID- 9615680
TI  - Dissection of a verbal abuser.

PMID- 9615681
TI  - Desensitization to nurse abuse.

PMID- 9615682
TI  - A prescription for health care.

PMID- 9615683
TI  - Nurturing the nurse on the path to success.

PMID- 9615684
TI  - Clinical restructuring. Patient focused care.

PMID- 9615685
TI  - Sexual harassment? Yes, please.

PMID- 9615686
TI  - Ominipotent. Omniscient paternalism.

PMID- 9615687
TI  - AIDS. The untold story.

PMID- 9615688
TI  - Surviving the toxic workplace with sabotage savvy.

PMID- 9615689
TI  - Symbolic expression in the workplace: protected speech or grounds for
      termination.

PMID- 9615690
TI  - Patient Safety Act.

PMID- 9615691
TI  - Do you have credibility?

PMID- 9615692
TI  - Exploring new frontiers in nursing.

PMID- 9615694
TI  - [Progress of acute liver failure and indications for liver transplantation].
AB  - OBJECTIVE: To analyse the course of acute liver failure and the indications for
      liver transplantation. PATIENTS AND METHODS: In 16 patients who developed acute
      liver failure between July 1992 and July 1997 the indications for liver
      transplantation and total survival time were analysed retrospectively. RESULTS:
      Intensive medical care (ventilation, dialysis) was necessary in 60% of the
      patients to bridge organ failure until liver transplantation. In 14 patients
      liver transplantation was indicated. Eleven of the patients, with a minimal Quick
      value of less than 10%, presented with the prognostically poorest London
      criteria. In two patients the combination of three additional criteria of the
      London classification led to liver transplantation being indicated. In one
      patient with Wilson's disease the transplantation was undertaken despite good
      clotting factor synthesis, because an encephalopathy occurred. In two patients
      liver transplantation was not undertaken even though indicated, in one because
      liver functions improved, in the other because necrotizing pancreatitis had
      occurred. In another patient, who had been poisoned by eating the mushroom
      Amanita phalloides, the attempted transplantation was cut short, because
      intestinal necrosis had developed, and the patient died during the operation.
      Nine of the eleven patients who had a transplantation and three of the four
      treated conservatively survived. CONCLUSION: The 60-day survival rate in this
      series, achieved in a recently established transplantation programme, is high (12
      of 16; 75%), being comparable to those in larger transplantation centres.

PMID- 9615695
TI  - [Intravascular ultrasound in recurrent myocardial ischemia and unremarkable
      coronary angiogram].
AB  - HISTORY AND CLINICAL FINDINGS: 3 months after sustaining an intramural anterior
      wall myocardial infarction (AWMI) a 57-year-old man was again admitted with the
      clinical and electrocardiographic (ECG) signs of an acute AWMI. As the activities
      of creatinine kinase (841 U/l) and of the myocardial isoenzyme (CKMB 143 U/l)
      were markedly elevated, thrombolysis with streptokinase was instituted.
      Subsequent left heart catheterization demonstrated discrete wall irregularity in
      the proximal branch of the anterior interventricular artery (PAIVA) and the right
      coronary artery, but no evidence of stenosing coronary heart disease. TREATMENT
      AND COURSE: Because of the discrepancy in the findings, intravascular ultrasound
      imaging (IVUI) was performed. It revealed an eccentric unstable plaque in the
      PAIVA with a minimal cross-sectional stenosis of 3.3 mm2 (50% luminal narrowing).
      After stent implantation under IVUI a good primary result was achieved (stent
      cross-sectional area 6.2 mm2). CONCLUSION: The usual cause of acute MI is rupture
      of an unstable, not flow-limiting and thus angiographically possibly "silent"
      plaque. IVUI can provide immediate assessment of atheromatous wall changes and
      can thus help to decide on further specific interventional measures.

PMID- 9615696
TI  - [Tsutsugamushi fever. Rare rickettsiosis after a stay in the Philippines].
AB  - HISTORY AND CLINICAL FINDINGS: After returning to his native Germany from a
      holiday in the Philippines a 37-year-old man was admitted because of high fever,
      cervical lymphadenopathy, pharyngitis and conjunctivitis, transient skin rash,
      nausea and vomiting, leukocytosis with shift to the left, atypical lymphocytes,
      as well as increased transaminases, LDH and cholestasis-indicating enzymes.
      INVESTIGATIONS: Stool, sputum and urine cultures were negative. The chest
      radiogram showed bilateral mild interstitial infiltration. Antibody titres
      against Rickettsia tsutsugamushi were markedly raised (IgG 1:128, IgM 1:2048).
      DIAGNOSIS, TREATMENT AND COURSE: Empirical antibiotic treatment with
      ciprofloxacin (200 mg twice daily intravenously) had no effect. As the mild signs
      of interstitial pneumonia progressed, clarithromycin (500 mg twice daily orally)
      was substituted with rapid fall in fever and gradual improvement. Tsutsugamushi
      infection was diagnosed serologically and the antibiotic changed to doxycycline
      (100 mg twice daily orally), continued for 14 days. Full remission occurred.
      CONCLUSIONS: Tsutsugamushi fever should be included in the differential diagnosis
      if, in addition to a history of a visit to an endemic area, there is the clinical
      triad of skin necrosis at the site of a mite bite, regional lymphadenopathy and
      skin rash (in this case, no skin lesion). The infection can be lethal without
      adequate treatment. Tetracyclines and possibly also macrolide antibiotics are
      effective against the causative organism.

PMID- 9615697
TI  - [Perioperative blood loss--the role of the anesthetist].

PMID- 9615698
TI  - [Medical explanations for patients with malignant diseases].

PMID- 9615699
TI  - [Dyspepsia in the elderly. Initial endoscopy or empirical therapy?].

PMID- 9615700
TI  - [Renal effectiveness of non-steroidal anti-inflammatory agents].

PMID- 9615702
TI  - [LE cell death].

PMID- 9615701
TI  - [Benefits of early nephrological management of chronic renal failure].
AB  - OBJECTIVES: We evaluated whether early nephrological referral of patients with
      chronic renal failure (CRF) resulted in improved condition of patients at
      initiation of maintenance dialysis and in better outcome on dialysis. PATIENTS
      AND METHODS: We prospectively recorded clinical status, laboratory parameters,
      length of hospital stay and outcome of 900 CRF patients who started maintenance
      dialysis at Necker hospital between January 1989 and December 1996. We compared
      patients who benefited regular nephrological follow-up, and patients who were
      referred in emergency conditions at the ultimate stage of CRF. RESULTS: Among the
      900 patients, 731 (81.2%) had regular nephrological follow-up, including 632
      (70.2%, group IA) with optimal preparation to dialysis and 99 (11%, group IB)
      whose clinical course was complicated due to heavy comorbidity, whereas 169
      (18.8%, group II) had no previous nephrological management. Over the 8-year
      observation period, the proportion of the latter group did not decrease. Late
      referred patients had higher blood pressure level, more frequent fluid overload,
      higher serum levels of urea, creatinine, uric acid and phosphate, and lower
      levels of bicarbonate, calcium, albumin and creatinine clearance that did well
      prepared patients. Mean (+/- SD) hospital stay was 29.7 +/- 15.8 days in the
      former compared to only 4.8 +/- 3.3 days (p < 0.001) in the latter. Early deaths
      within 3 months of dialysis initiation were more frequent (7.1 vs 1.6% p < 0.05)
      and less patients subsequently were able to be treated out-center (20.1 vs 40.7%,
      p < 0.05) in group II than in group IA. The overcost induced by late referral may
      be estimated at 0.25 million French francs per patient. CONCLUSION: An
      unjustified late nephrological referral of CRF patients still is observed in
      nearly 20% of cases. Such late referral is detrimental to both patients in terms
      of altered quality of life and long hospital stay, and to the collectivity due to
      heavy overcost. Closer cooperation between family physicians and nephrologists is
      needed to provide optimal management and allow timely preparation to maintenance
      dialysis of CRF patients.

PMID- 9615703
TI  - [Restless upper limb syndrome].

PMID- 9615704
TI  - [Informed consent: what is the question? Correlation between practice and
      theory].
AB  - Informed consent in medical or human experimentation is a concept generally
      accepted by most doctors. The foundation of informed consent is self
      determination and, in the legal setting of France, contractual agreement. The
      practical application of informed consent in medical specialities such as
      psychiatrics or intensive care raises difficult problems subject to much debate.
      Contemporary history would suggest that the strength of informed consent may be
      highly insufficient to avoid the risk of dictated power dominating-patients. In
      order to find a solution to these problems, the field of action of informed
      consent must be widened. We propose here to define informed consent as one of
      many means to defend patient dignity and human rights.

PMID- 9615705
TI  - [Apropos of BCG].

PMID- 9615706
TI  - [Kaposi disease].

PMID- 9615707
TI  - Spontaneous and radiation-induced apoptosis in lung carcinoma cells with
      different intrinsic radiosensitivities.
AB  - Spontaneous and radiation-induced apoptosis in three lung carcinoma cell lines (U
      1285, U-1906 and U-1810) with previously characterised intrinsic
      radiosensitivities (RS) was assessed by TUNEL-staining, detection of DNA
      laddering and cleavage of poly-(ADP-ribose) polymerase (PARP). Spontaneous
      apoptosis was detected at a high level in the radiosensitive U-1285, at an
      intermediate level in U-1906 and not detected in the radioresistant U-1810 cell
      line. Radiation-induced apoptosis, assessed by TUNEL assay, was present in U-1285
      and U-1906 cells but not in U-1810 cells. To explain these findings, expression
      of Bcl-2, Bax, c-Myc and RB protein and mutations of the p53 gene were analysed.
      The ratio Bcl-2/Bax was higher in U-1810 cells compared with U-1285 and U-1906
      cells. Overexpression of c-Myc and loss of RB was found in U-1285 cells whereas
      both U-1906 and U-1810 cells expressed RB and showed lower c-Myc expression.
      Analysis with sequencing of all p53 exons disclosed mutations in all three cell
      lines. Thus, apoptosis was a p53 independent process in U-1285 and U-1906 cells.
      RB loss and overexpression of c-Myc may enhance apoptosis in U-1285 cells. Our
      data suggest that spontaneous apoptosis may correlate with RS in SCLC.

PMID- 9615708
TI  - Expression analysis of protein kinase C isozymes and multidrug resistance
      associated genes in ovarian cancer cells.
AB  - We recently demonstrated a correlation between the expression levels of the PKC
      eta isozyme and the MDR1 or MRP genes in blasts from AML patients, and in primary
      breast cancers. In order to extend these findings we analysed ovarian cancer
      cells from 14 ascites aspirates from 8 patients using a cDNA-PCR approach. 5
      patients were examined in follow up studies. 4 out of these 5 patients received
      continuous chemotherapy. The relative increases in MDR1, MRP, LRP or PKC eta mRNA
      expression levels were monitored. In one of these patients combined significant
      increase in MDR1, MRP, LRP and PKC was seen. One follow up sample was obtained
      after chemotherapy was discontinued. In this case significant relative decreases
      of MDR1, LRP and PKC eta mRNA expression levels were found. Furthermore, a
      significant positive correlation was determined for the relative mRNA expression
      levels of MRP and PKC eta. These results point to a multifactorial emergence of
      MDR in this type of tumor with a possible involvement of the PKC eta isozyme.

PMID- 9615709
TI  - Deletion of chromosome 3p is an early event in malignant progression of cervical
      cancer.
AB  - BACKGROUND: Loss of chromosome 3p has been reported to be a common genetic
      alteration in certain types of tumors as well as in cervical cancer. To
      understand its role in multistep cervical carcinogenesis, we analysed the allelic
      loss of this chromosome region in early pre-invasive cervical neoplastic lesions.
      MATERIALS AND METHODS: 49 cases comprising two types of pre-invasive lesions
      (without and with coexisting invasive cancer) were selected. Chromosome 3p
      deletios in selected neoplastic lesions were detected by PCR-RFLP combined with
      morphologically guided microdissection technique for DNA preparation. RESULTS:
      DNA samples from 40 cases out of 49 were successfully amplified and found to be
      heterozygotes at least in one chosen chromosome marker. Of 19 cases without
      coexisting cancer, LOH was detected in 4 cases(21%) and 3/17(18%) precancerous
      lesions (1 moderate dysplasia, 2 severe dysplasias) and 1/5(20%) carcinomas-in
      situ. A significantly higher rate of allelic loss was observed in pre-invasive
      lesions adjacent to invasive cancer, showing 29%(4/14) in precancerous lesion and
      67%(2/3) in carcinoma-in-situ. Analysing the invasive cancer and synchronous pre
      invasive neoplasia, LOH was found to occur at early precursor stage in the
      majority of cases(5/7). The most frequently lost locus in cervical cancer is the
      chromosome regions detected by marker D3S30(60%) and D3F15S2(47%), suggesting a
      candidate tumor suppressor gene, which may play a role in cervical
      carcinogenesis, is harboured on this chromosome region. CONCLUSIONS: Our results
      confirm the high frequency of chromosome 3p allelic loss in cervical cancer and
      suggest that this genetic alteration is an early event in the development of
      cervical cancer and may potentially serve as a marker of risk for progression of
      premalignant lesions to invasive cancer.

PMID- 9615710
TI  - Improvement of gene therapy for ovarian cancer by using acyclovir instead of
      ganciclovir in adenovirus mediated thymidine kinase gene therapy.
AB  - Adenovirus(ADV) mediated thymidine kinase(TK) gene therapy followed by
      ganciclovir(GCV) administration is widely used in different types of cancer. ACV
      shares the same mechanism of selective cell killing in ADV/TK positive cells as
      GCV and can be used at 4.5 times higher doses in patients without significant
      side effects. An increased dose of TK substrate is associated with improved
      bystander effect and more efficient cell killing. Toxicity and cell killing
      efficacy were assessed using a 3-(4,5-dimethylthiazol)-2,5-diphenyl tetrazolium
      bromide(MTT) based assay in three ovarian cancer cell lines with different
      proliferation patterns. At the same concentration, equal or higher cell killing
      efficacy and bystander effect were observed using ACV rather than GCV. 2.5 and 5
      times (25 micrograms/ml and 50 micrograms/ml) higher concentrations of ACV always
      resulted in more effective cell killing than GCV (10 micrograms/ml, P < 0.01).
      Our data indicate that replacing GCV with ACV in the ADV-TK gene therapy may
      increase the treatment effect without increasing toxicity.

PMID- 9615711
TI  - The efficacy of adenovirus-mediated gene therapy of ovarian cancer is enhanced by
      using the cytomegalovirus promoter.
AB  - The cytomegalovirus(CMV) promoter is considered one of the strongest positive
      regulators. In this study toxicity, cell killing efficacy and bystander effect of
      Rous Sarcoma Virus(RSV) driven herpes simplex thymidine kinase(TK) gene therapy
      was compared with CMV driven TK gene therapy in three ovarian cancer cell lines
      with different growth patterns using a 3-(4,5-dimethylthiazol)-2,5-diphenyl tetra
      zolium bromide (MTT) based assay. ADV/CMV-TK was shown to be 2 to 10 times more
      effective in tumor cell killing than ADV/RSV-TK. The difference in cell killing
      efficacy between ADV/CMV-TK and ADV/RSV-TK was dependent on the individual cell
      line. A CMV promoter dependent eight to ten fold improvement in cell killing
      efficacy was observed in the relatively slow growing SKOV3 cell line which is not
      easily transducible, while only a 2 to 4 fold difference was observed in the
      easily transducible OV-CA-2774 and OV-CA-1225 cell lines. ADV/CMV-TK also showed
      a stronger bystander effect than ADV/RSV-TK in all three ovarian cancer cell
      lines. Our data demonstrated that the efficacy of adenovirus-mediated gene
      therapy of ovarian cancer can be enhanced by using the CMV promoter without
      increasing toxicity.

PMID- 9615712
TI  - The synergism of 6-mercaptopurine plus cytosine arabinoside followed by PEG
      asparaginase in human leukemia cell lines (CCRF/CEM/0 and (CCRF/CEM/ara-C/7A) is
      due to increased cellular apoptosis.
AB  - BACKGROUND: The only effective drug against ALL that inhibits protein synthesis
      is Asparaginase (ASNase). The drug depletes asparagine (Asn) in serum and cells
      and since the leukemic T-cells (thymic origin cells) lack asparagine synthetase,
      the amino acid starvation leads to apoptosis. When PEG-ASNase is combined with
      antimetabolite drugs such as ara-C, or combinations of 6-MP followed by ara-C, it
      augments the cytotoxic effect synergistically against human T-leukemia cells.
      MATERIALS AND METHODS: Synergism studies with two- or three-drug combination
      regimens in the human leukemia cell lines, CEM/0 and CEM/ara-C/7A have been
      investigated along with its effect in inducing apoptosis. RESULTS: The IC50
      (approximately Dm) values of ara-C were 0.032 microM and 0.11 microM, and that of
      PEG-ASNase were 0.002 IU/ml and 1.52 IU/ml against CEM/0 and CEM/ara-C/7A cells,
      respectively. Thus, CEM/ara-C/7A cell line that is partially resistant to ara-C
      exhibited 681-fold cross-resistant to PEG-ASNase as compared to CEM/0. The
      concurrent drug exposure of ara-C and PEG-ASNase for 48 hours resulted in IC50
      values of 0.56 nM for ara-C and 0.56 mIU/ml for PEG-ASNase respectively, in CEM/0
      cells which represents a 57.4-fold synergism compared to ara-C alone. In the
      CEM/ara-C/7A cell line, the co-incubation with these two drugs resulted in IC50
      value of 0.015 microM for ara-C and 0.015 IU/ml for PEG-ASNase respectively, or a
      7.25-fold synergism as compared to ara-C and 101.1-fold synergism in comparison
      with PEG-ASNase alone. Pre-clinical studies involving three-drug combination
      consisting of 6-MP, ara-C and PEG-ASNase in a sequence-specific manner showed a
      15.6-fold synergism against CEM/0 cell line over the two-drug combination of 6-MP
      followed by ara-C or approximately 160-fold syneryism over ara-C alone.
      CONCLUSION: The two-drug combination of ara-C and PEG-ASNase or the three-drug
      combination of 6-MP, ara-C and PEG-ASNase in the ara-C sensitive and resistant
      cell line showed significant drug synergism and CEM/ara-C/7A cells exhibited
      collateral sensitivity to PEG-ASNase. The three-drug combination also induced
      dose-dependent apoptotic DNA fragmentation which was higher than the two-drug
      combination of 6-MP and ara-C. We also conclude that the sequence specific use of
      PEG-ASNase in combination with the nucleoside analog drugs may benefit leukemia
      patients in early relapse.

PMID- 9615713
TI  - Avoidance of doxorubicin resistance in osteosarcoma cells using a new quinoline
      derivative, MS-209.
AB  - P-glycoprotein (Pgp), a membrane drug efflux pump, is thought to be responsible
      for the observed drug resistance in osteosarcoma. We have recently developed Pgp
      positive, multidrug resistant (MDR) murine osteosarcoma cell lines, which may be
      suitable models for the study of drug resistance in osteosarcoma. In this study,
      we investigated the effect of a newly synthesized quinoline compound, MS-209, on
      the reversal of doxorubicin (DOX) resistance in these cell lines. Three different
      types of resistance modifying agents (RMAs) as well as MS-209 were studied. These
      included the calcium channel blocker verapamil, and the immunosuppressive agents
      cyclosporin A and FK506. The reversal effects of the RMAs on DOX resistance were
      assessed by the MTT assay. In the absence of RMAs, the MDR osteosarcoma cells
      were 20-fold more resistant to DOX than the parental cells. When MS-209 was added
      at a final concentration of 0.1 to 3 microM to the MDR cells, 3-to 74-fold
      sensitization was observed. A complete reversal (37-fold sensitization) of the
      resistance was obtained at 1 microM MS-209. This concentration of MS-209 was 3-,
      8- and 28-fold more effective than the same concentration of FK506, verapamil and
      cyclosporin A, respectively. These results indicate that MS-209 may be a more
      effective RMA, and that DOX resistance in osteosarcoma cells could be reversed by
      comparatively low doses of MS-209.

PMID- 9615714
TI  - MMP-2 expression is associated with, but not sufficient for, malignant conversion
      of murine LTA cells.
AB  - We previously showed that tumorigenic, non-metastatic LTA cells can be converted
      to a metastatic phenotype either by cell fusion with non-malignant NIH 3T3 cells,
      or by transfection with genomic DNA from metastatic murine B16F1 or human 1GR37
      melanoma cells. In order to identify a gene present in NIH 3T3 cells that is
      responsible for this conversion, we transferred DNA from an NIH 3T3 genomic
      library into LTA cells and tested for changes in metastatic properties, assessed
      in the chick embryo. We found that 3 of 4 pools of transfectant clones showed
      significantly increased metastatic ability over the vector-only control
      transfectants. All three metastatic transfectant pools showed significantly
      increased RNA levels of the 72 kDa type IV gelatinase (MMP-2). To test whether
      increased expression of MMP-2 was sufficient to convert LTA cells to metastatic
      ability, we transfected full length MMP-2 cDNA, in a CMV-promoter expression
      construct, into LTA cells. Stable transfectants with elevated MMP-2 RNA and
      enzymatic activity were obtained. The highest MMP-2 expressing clone was assayed
      for experimental metastatic ability in the chick embryo, and found to be no more
      metastatic than LTA parental cells. We conclude that increased MMP-2 expression
      accompanies the malignant conversion of LTA cells, but MMP-2 expression alone is
      not sufficient to bring about this change. The inability of LTA cells to
      metastasize thus appears to be due to a more complex defect than insufficient MMP
      2. This study supports the idea that malignant conversion may require the
      concerted activation of multiple genes, which are in turn controlled by
      regulatory genes, whose identification will be important in understanding and
      controlling metastasis.

PMID- 9615715
TI  - Roscovitine inhibits the proliferative activity of immortal and neoplastic human
      breast epithelial cells.
AB  - [2-(R)-(1-Ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylp urine]
      (roscovitine) is a potent and selective inhibitor of cyclin-dependent kinases
      cdc2 and cdk2. In this study, we evaluated the potential involvement of this
      novel cyclin-dependent kinase inhibitor in the proliferative activity of
      malignant and non-malignant human breast epithelial cells in vitro. Estrogen
      receptor-positive MCF-7 breast carcinoma cells, immortalized estrogen receptor
      negative breast epithelial cells and highly malignant estrogen receptor-negative
      MDA-MB-231 breast epithelial cells, were incubated with different concentrations
      of roscovitine ranging from 1 to 40 micrograms/ml, and cell numbers were measured
      with the WST-1 colorimetric assay after 24, 48, 72, 96, 120, and 144 hours of
      treatment. Our results demonstrated that roscovitine inhibited the proliferation
      of human breast epithelial cells in a dose- and time-dependent manner.
      Roscovitine treatment decreased the number of viable cells and prevented the
      exponential growth of all the cell lines examined. The antiproliferative effect
      of this potent cdk inhibitor was independent of the estrogen receptor status of
      the cells. These data suggest that roscovitine is a potential antiproliferative
      drug for the treatment and/or prevention of both estrogen responsive and non
      responsive breast cancers.

PMID- 9615716
TI  - Synthesis and cytotoxic activity of new peptides containing basic amino acid
      residues.
AB  - In search of more potent compounds endowed with a cytotoxic activity, a new
      series of basic peptides was synthesized using solid-phase methods. All peptides
      were purified by preparative reverse-phase HPLC and characterized by electrospray
      mass spectrometry. The cytotoxic activity was determined in cultured HeLa cells.
      The hexadecapeptides 5 and 6 showed a 50% inhibition at the concentration of 30
      micrograms/ml. The salmina and the polyamino acids of L-arginine, L-histidine and
      L-lysine, containing sixteen residues, were virtually inactive. This demonstrates
      that a specific peptide sequence is necessary to obtain a positive response in
      HeLa test.

PMID- 9615717
TI  - Production of a motility factor by a newly established lung adenocarcinoma cell
      line.
AB  - We have established and characterised a cell line, designated WART, from a
      patient with primary adenocarcinoma of the lung. This cell line grows with a
      doubling time of approximately 15 hours, forms colonies in soft agarose, is
      tumorigenic in athymic nude mice, and has a complex karyotype with both
      structural and numerical abnormalities. WART serum free conditioned medium (SFCM)
      contains a factor which stimulates motile behavior of WART cells. This factor
      with an apparent molecular weight of 67 kDa induced in an autocrine fashion
      prominent pseudopodia, and chemotactic and chemokinetic responses. Heparin
      affinity chromatography, ion exchange and molecular sieve chromatography
      accompanied by SDS-PAGE analysis showed that the motility inducing activity was
      associated with a major band with molecular weight 67 kDa. The motility inducing
      activity of the 67 kDa protein was not sensitive to reduction with either
      dithiotreitol or mercaptoethanol which distinguishes it from A-2058 melanoma
      autocrine motility factor (AMF)/autotaxin, HT-1080 fibrosarcoma AMF and scatter
      factor which lose their biological activity upon reduction. This 67 kDa motility
      inducing factor did not augment DNA synthesis indicating that its locomotor
      activity is independent of mechanisms regulating cell growth. Pertusis toxin
      inhibited the motile response induced by the 67 kDa protein indicating a signal
      transduction pathway involving G proteins. Due to its production of the motility
      stimulating protein the cell line could facilitate studies of invasion and
      metastasis of human lung tumors.

PMID- 9615718
TI  - Screening of potential cancer preventing chemicals as antioxidants in an in vitro
      assay.
AB  - We used an azo-initiated fluorescence assay to rank a series of antioxidants,
      with the objective of selecting compounds for further evaluation as
      chemopreventive agents. Trolox was the positive control for the assay and, with
      an IC50 of 0.50 microM, was more active than any of the other 16 compounds
      examined. Three compounds, U83836E, glutathione, and purpurgallin, were only
      slightly less active with IC50's in the 1-3 microM range. Four other compounds
      were almost as active: protochatechuic acid, N-acetyl-L-cysteine, U74389G, and
      lipoic acid (reduced). This fluorescence-based assay for antioxidant activity is
      a rapid, economical way of ranking antioxidants for further development in the
      National Cancer Institute's chemoprevention program.

PMID- 9615719
TI  - Non-small cell lung cancer cycloxygenase activity and proliferation are inhibited
      by non-steroidal antiinflammatory drugs.
AB  - The effects of non-steroidal antiinflammatory drugs (NSAIDs) on non-small cell
      lung cancer (NSCLC) were investigated. Arachidonic acid (AA) was metabolized to
      prostaglandin E2 (PGE2) in NSCLC cells. NSAIDs such as aspirin or indomethacin
      reduced PGE2 levels in NCI-H157 and H1264 cells, and the decrease caused by PGE2
      was reversed by epidermal growth factor (EGF). By RT-PCR, both cyclooxygenase
      (COX)-1 and COX-2 mRNAs are detected in NCI-H157 and H1264 cells. By Northern
      analysis, COX-2 mRNA was induced by EGF and phorbol ester. By
      immunocytochemistry, COX-1 and COX-2 enzymes were localized to NSCLC tumors.
      Aspirin, indomethacin and ibuprofen decreased NSCLC growth in vitro. Aspirin and
      indomethacin inhibited proliferation of NSCLC xenografts in nude mice. These data
      suggest that COX enzymes may be important regulatory components of NSCLC.

PMID- 9615720
TI  - Shikonin, an ingredient of Lithospermum erythrorhizon, inhibits angiogenesis in
      vivo and in vitro.
AB  - Angiogenesis is critical for tumor growth and inflammation. Shiunko is a Chinese
      herbal ointment used for the treatment of burns in Japan. Its main ingredient is
      the root of Lithospermum erythrorhizon, which had been used for treating tumors
      and inflammation in China since the 5th century. We report here that shikonin,
      the main chemical ingredient of L. erythrorhizon is a novel inhibitor of
      angiogenesis. It inhibited tumor necrosis factor-alpha-induced and B16 melanoma
      induced angiogenesis in mice and normal developmental angiogenesis in the yolk
      sac membranes of chick embryos. Shikonin also inhibited proliferation and
      migration of endothelial cells in culture and network formation by endothelial
      cells on Matrigel in vitro. The dose-responsive study suggests that the mechanism
      of this inhibitory effect on angiogenesis involves the prevention of network
      formation by endothelial cells via blocking integrin alpha v beta 3 expression.

PMID- 9615721
TI  - Five-lipoxygenase inhibitors reduce Panc-1 survival: the mode of cell death and
      synergism of MK886 with gamma linolenic acid.
AB  - The 5-lipoxygenase inhibitors ETYA, SC41661A and MK886 reduced the proliferation
      and viability of Panc-1 human pancreatic cancer cells. The extent of inhibition
      depended upon drug concentration, and with continued culture, cells detached and
      stained with trypan blue. Although results from flow cytometry were those
      associated with programmed cell death, despite repeated attempts, no DNA
      laddering consistent with its later stages was detected, and studies with the
      TUNEL assay were negative. Light and electron microscopy of cells cultured with
      SC41661A provided morphologic evidence of a population of "dark" cells and of an
      incompletely expressed type 1 programmed cell death including margination of
      chromatin at the nuclear membrane and by consolidation and degeneration of
      cytoplasmic organelles, along with extensive vacuolization. Cells cultured with
      MK886 exhibited compact "dark" cells and an unusual cytoplasmic mode of cell
      death characterized by vacuolization and widely separated smooth internal
      membranes without diagnostic nuclear changes. This is in marked contrast to the
      extensive type 1 PCD induced by 5-lipoxygenase inhibitors cultured with human
      U937 monoblastoid cells. On balance, the response of Panc-1 cells to MK886
      suggests expression of a variant type 2 (autophagic) cellular suicide, although
      some contribution from components of a "cytoplasmic" (type 3?) form of non
      necrotic cell death may also be considered. In a European clinical trial, gamma
      linolenic acid, a polyunsaturated fatty acid that generates free radicals has
      been combined with 5-fluorouracil as chemotherapy for pancreatic cancer. Panc-1
      cell proliferation was insensitive to inhibition by several chemotherapeutic
      agents employed clinically, including 5-fluorouracil, cisplatin or gemcitabine
      and only somewhat sensitive to GLA. When gamma linolenic acid was combined with
      MK886, the more effective of the two 5-lipoxygenase inhibitors, a synergistic
      reduction in Panc-1 cell number and viability occurred.

PMID- 9615722
TI  - Study of bcl-2 protein expression and the apoptosis phenomenon in neuroblastoma.
AB  - BACKGROUND: Prognosis in neuroblastoma is based upon several clinical factors
      such as age, tumoral staging and other genetic factors like N-myc oncogene
      amplification or deletion of the short arm of chromosome 1 (del 1p). Recent
      reports indicate that bcl-2 protein expression is associated with a poor outcome
      in patients with neuroblastoma. MATERIALS AND METHODS: We present a study of 80
      cases from the files of the Spanish neuroblastoma study group (N-II-92) analysing
      bcl-2 protein expression by means of immunohistochemical methods and its relation
      with other parameters such as histopathology, PCNA expression, N-myc
      amplification and DNA study of apoptosis. RESULTS: We found a statistical
      correlation between bcl-2 protein expression and unfavourable histopathology, N
      myc amplification and PCNA nuclear staining. An inverse relation between bcl-2
      staining and apoptosis was detected. CONCLUSIONS: Based on present findings it
      can be concluded that the determination of bcl-2 protein provides prognostic
      information when associated with other biological factors involved in
      neuroblastomas.

PMID- 9615723
TI  - TPA-mediated regulation of osteopontin in human malignant glioma cells.
AB  - Malignant gliomas are the most common primary intracranial neoplasms in adults
      and are largely refractory to post-surgical therapy despite intensive therapeutic
      efforts. Using a number of different brain tumor-derived cell lines we have
      demonstrated that the mRNA for osteopontin (OPN), which is substantially over
      expressed by some tumors in comparison with normal tissues, is preferentially
      expressed in high grade and metastatic brain tumors compared to low grade brain
      tumors. One glioma-derived cell line, U105MG, which does not express significant
      amounts of OPN mRNA, could be induced dose-dependently by the tumor-promoting and
      PKC-activating phorbol ester, TPA, to over-express OPN mRNA in a PKC-dependent
      manner. Unexpectedly, treatment of U105MG cells with Ca2+ ionophore (A23187)
      completely inhibited TPA-mediated induction of OPN while treatment with the
      intracellular Ca2+ antagonist TMB-8 had no significant effect. Elucidation of
      regulatory mechanisms for OPN induction in glioma cells should facilitate
      rational design of novel therapeutics for human malignant gliomas.

PMID- 9615724
TI  - Inhibition of experimental lung metastasis of murine colon carcinoma cells
      depends on the amount of interleukin-2 secreted from the transduced cells.
AB  - We examined the antitumor effect of low and high interleukin-2 (IL-2) producers
      of murine colon carcinoma cells (Colon 26) which were generated by transduction
      with IL-2 gene in an experimental lung metastasis model using syngeneic mice.
      Intravenous injection of the low IL-2 producer cells formed multiple lung
      metastatic foci and the survival of the mice was not different from that of the
      mice injected with wild-type cells. However, the mice administrated with the high
      producer cells survived significantly longer. Subcutaneous inoculation of the low
      producers, although it caused the development of local tumors at the inoculation
      sites in some of the mice tested, inhibited lung metastasis of wild-type cells
      subsequently inoculated and prolonged the survival of the mice rechallenged with
      Meth A cells, syngeneic fibrosarcoma cells. In contrast, inoculation of the high
      producers did not cause the development of subcutaneous tumors and inhibited the
      experimental metastasis of parental but not Meth A cells inoculated thereafter.
      Thus, the amount of secreted IL-2 from tumor cells differentially influences
      antitumor effects by inducing tumor specific and nonspecific immunity.

PMID- 9615725
TI  - Ascorbic acid recycling in N-myc amplified human neuroblastoma cells.
AB  - The present study investigated the ability of two neuroblastoma cell lines (SK-N
      SH, with one copy of N-myc, and SK-N-BE(2), with over 150 copies of N-myc) to
      recycle ascorbate by quantifying semidehydroascorbate reductase and
      dehydroascorbate reductase activities. Both cell lines expressed dehydroascorbate
      activity (SK-N-SH 28.4 +/- 9.8, SK-N-BE(2) 21.7 +/- 5.2 nmol/min/mg protein).
      Intracellular semidehydroascorbate activity was present only in SK-N-BE(2) cells
      (4.7 +/- 1.2 nmol/min/mg protein). Extracellular ascorbate was regenerated by
      semidehydroascorbate membrane activity, the activity of SK-N-BE(2) being twice
      that of SK-N-SH cells. The present data may explain the ability of the tumor to
      progress or regress through mechanisms involving both myc oncogene and apoptosis.

PMID- 9615726
TI  - Effects of the antitumor agent perillyl alcohol on H-Ras vs. K-Ras farnesylation
      and signal transduction in pancreatic cells.
AB  - BACKGROUND: Perillyl alcohol has chemotherapeutic activity against pancreas
      cancers that have a K-ras oncogene, and it inhibits the prenylation of Ras and
      other proteins in many cell types. MATERIALS AND METHODS: We tested the
      hypothesis that perillyl alcohol would impair Ras farnesylation and Ras signal
      transduction pathways in pancreatic tumor cells. RESULTS: In B12/13 pancreatic
      tumor cells that had a K-ras oncogene, perillyl alcohol inhibited total protein
      prenylation and decreased Ras farnesylation. However, the decrease in Ras
      farnesylation was not sufficient to affect Ras GTP/GDP ratios or MAP kinase
      phosphorylation. We then investigated the effects of perillyl alcohol on H-Ras
      vs. K-Ras. Interestingly, H-Ras, but not K-Ras, farnesylation was inhibited by
      perillyl alcohol, and perillyl alcohol inhibited MAP kinase phosphorylation in H
      ras but not K-ras oncogene-transformed pancreatic cells. CONCLUSIONS: The
      antitumor activity of perillyl alcohol against pancreatic cancers may stem from
      its ability to inhibit the prenylation of growth-regulatory proteins other than K
      Ras, including H-Ras.

PMID- 9615727
TI  - Salmonella mutagenicity of musk ambrette depends on both microsomal and bacterial
      enzyme activity.
AB  - Former studies revealed musk ambrette as a mutagen in Salmonella typhimurium TA
      100 in the presence (+S9) but not in the absence (-S9) of an exogenous
      metabolizing system. To clarify the role of bacterial nitroreductases (NR) in the
      toxification of musk ambrette to mutagenic metabolites the compound was examined
      with the Salmonella/mammalian microsome assay using the NR deficient strain
      S.typhimurium TA 100 NR in the presence and absence of S9. Musk ambrette showed
      mutagenicity in Salmonella typhimurium TA 100 (+S9) but no mutagenicity in the NR
      deficient strain TA 100 NR (+S9). Additionally, no mutagenicity was detected in
      both TA 100 (-S9) and TA 100 NR (-S9). These results indicate the need for both
      mammalian microsomal enzymes and bacterial nitroreductases to cause the
      mutagenicity of musk ambrette.

PMID- 9615728
TI  - Radical scavenging activity of Acer nikoense Maxim. extract.
AB  - The effect of hot water and alkaline extracts of Acer nikoense Maxim. on the
      radical intensity of sodium ascorbate, superoxide anion (O2-)(produced by
      hypoxanthine-xanthine oxidase reaction) and hydroxyl radical (-OH)(generated by
      Fenton reaction) was investigated using ESR spectroscopy. All these extracts
      produced radical(s) under alkaline conditions and enhanced the radical intensity
      of sodium ascorbate. Among these fractions, Fr. I showed the highest stimulation
      effect, which coincided with its higher degradation rate and capacity to enhance
      the cytotoxic activity of ascorbate. These fractions also dose-dependently
      reduced the radical intensity of O2- and -OH. The present study demonstrates that
      Acer nikoense Maxim. extracts potentiate both radical intensity and apoptosis
      inducing activity of ascorbate.

PMID- 9615729
TI  - Detection of oestrogen and progesterone receptor expression in breast tumors by
      semiquantitative PCR.
AB  - BACKGROUND: Estimation of oestrogen receptors (ER) and progesterone receptors
      (PgR) by dextran-coated charcoal (DCC) or immunohistochemical methods have become
      standard practices in the management of breast cancer. MATERIALS AND METHODS: A
      "multiplex" polymerase chain reaction (PCR) system was developed for quantitative
      estimation of ER and PgR mRNA in breast tumour specimens. RESULTS: A
      statistically significant correlation could be found between the mRNA of the
      oestrogen and the progesterone receptor (p < or = 0.0001). Protein data defined
      in classes, compared with mRNA data showed a significant correlation for the
      oestrogen receptor (p < or = 0.0001) as well as for the progesterone receptor (p
      < or = 0.046). CONCLUSION: Messenger RNA could be determined by the present PCR
      system in tumours assayed as negative by DCC method. Therefore, this sensitive
      PCR procedure, which requires small amounts of material may be very useful as a
      diagnostic test to determine the choice of therapy.

PMID- 9615730
TI  - Adjuvant 131I-anti-CEA-antibody radioimmunotherapy inhibits the development of
      experimental colonic carcinoma liver metastases.
AB  - Adjuvant radioimmunotherapy (RIT) for human colonic cancer was performed in a
      nude rat model of experimental liver metastases. Thirty-three rats were injected
      intraportally through a mesenteric vein with 5 x 10(6) cells from the human
      colonic cancer cell line LS174T. Within half an hour, 20 MBq (n = 2), 75 MBq (n =
      5), or 150 MBq (n = 10) of the 131I-labelled anti- carcinoembryonic antigen (CEA)
      monoclonal antibody (MAb) 38S1 was administered intravenously (i.v.), whereas
      control groups received either i.v. saline injections (n = 12) or 150 MBq of the
      irrelevant 131I-labelled MAb 79C (n = 4). Decay corrected whole-body data showed
      that more than 80% of the initially MAb-bound radioiodine was excreted during the
      first 2 weeks. Whole- body clearance and blood clearance of 131I-38S1 and 131I
      79C were essentially similar. At sacrifice 5-7 weeks after administration,
      neither 20 MBq nor 75MBq 131I-38S1 significantly prevented the development of
      liver metastases. By contrast, with 150 MBq, no metastases formed in the animals
      treated with MAb 131I-38S1 or 131I-79C. A radiation induced effect on the
      haematopoietic system was found in the 150MBq dosage groups. It is concluded that
      the inhibition of tumour induction was not strictly dependent on a radiation dose
      delivered by a tumour-specific MAb. Since a non-tumour-specific 131I-MAb, in a
      smaller group of animals, proved equally efficacious in preventing tumour growth,
      the total body 131I dose was probably the major contributing factor.

PMID- 9615731
TI  - The mutation status of PAX3 and p53 genes in medulloblastoma.
AB  - The p53 and PAX3 genes were examined by PCR, SSCP and DNA sequencing methods in
      50 and 58 paraffinembedded medullablastoma tissues, respectively. Four novel
      mutations were identified among these samples in exon 5 of the p53 gene. Two
      tumours showed a G to A transition. One heterozygous mutation was located on
      codon 158 which changed the encoded amino acid from Arg (CGC) to His (CAC).
      Another was located on codon 174 and replaced AGG (Arg) with AAG (Lys). There was
      a single base deletion of guanine located on codon 160 in another two samples,
      causing a frameshift. This is the first study of mutation status of PAX gene in
      medulloblastoma wherein only one polymorphism was identified in the gene. The
      polymorphism changed codon 43 from GGC to GGT but both encoded glycine.

PMID- 9615732
TI  - Effects of suramin on polyamine metabolism in B16 murine melanoma cells.
AB  - Polyamines and their biosynthetic enzymes, such as ornithine decarboxylase (ODC)
      and S-adenosylmethionine decarboxylase (AdoMetDC), are crucial for normal and
      neoplastic cell growth and differentiation. Suramin inhibits the growth of
      several tumor cells by affecting various intracellular targets, but its effects
      on polyamines are not known. In this study, the effects of suramin on some
      parameters of polyamine metabolism in B16 melanoma cells were investigated in
      vitro. Suramin increased cellular ODC activity and ODC mRNA levels, whereas the
      drug was directly inhibitory to the enzyme. AdoMetDC was not affected. Cellular
      putrescine levels were enhanced by suramin, whereas spermidine and spermine pools
      were unaltered. Cells cultured in the presence of suramin showed decreased
      cellular polyamine transport, but no direct inhibitory effect on the polyamine
      transporter could be found. Fluorescence spectroscopy demonstrated a direct
      interaction between suramin and spermine. It may be concluded that suramin
      affects polyamine metabolism, and that its effects in some respects are opposite
      to those of alpha-difluoromethylomithine (DFMO), a specific inhibitor of ODC.

PMID- 9615733
TI  - Opposing effects of suramin and DL-alpha-difluoromethylornithine on polyamine
      metabolism contribute to a synergistic action on B16 melanoma cell growth in
      vitro.
AB  - Polyamines are crucial for normal and neoplastic cell growth. Treatment with the
      polyanionic drug suramin has pronounced antigrowth activity in several tumor cell
      lines, but its clinical use has been hampered by its toxicity. We have earlier
      shown that suramin affects cellular polyamine metabolism and transport, and that
      these effects were, in some respects, opposite to those of alpha
      difluoromethylomithine (DFMO), a specific inhibitor to ornithine decarboxylase, a
      key metabolic enzyme for polyamines. DFMO has been used in anticancer trials,
      although with limited success. Combinations of suramin and DFMO were, hence,
      evaluated in vitro and were found to strongly inhibit B16 melanoma cell
      proliferation. DFMO alone induced melanoma cell differentiation, and suramin used
      in combination with DFMO did not abrogate this DFMO-induced differentiation.
      Synergy analysis demonstrated a pronounced growth-inhibitory synergism between
      suramin and DFMO. The results suggest that the efficacy of combinations of DFMO
      with suramin or its analogues should be further explored, especially in cells
      requiring high levels of polyamines for their growth.

PMID- 9615734
TI  - Effects of tamoxifen on mammary tumors and bone in 7,12-dimethylbenz
      (a)anthracene-treated rats.
AB  - We investigated the effects of tamoxifen on the growth of 7,12
      dimethylbenz(a)anthracene induced rat mammary tumors, the activity of thymidylate
      synthetase and thymidine kinase (key enzymes involved in de novo and salvage
      pathways for pyrimidine nucleotide synthesis), and also their gene expression.
      The effects on immunohistochemistry using bromodeoxyuridine in the tumors and
      bone mineral density of the femur in rats were also studied. Chronic
      administration of tamoxifen markedly reduced the expression of thymidylate
      synthetase mRNA, followed by a reduction in enzyme activity and S-phase cells in
      the mammary tumors, and significantly enhanced the bone mineral density.
      Tamoxifen not only attenuated bone loss in aging but also enhanced bone volume in
      mammary tumor-bearing rats in which tumor growth was suppressed via both the de
      novo and salvage pathways for pyrimidine nucleotide synthesis.

PMID- 9615735
TI  - Epidermal cell adhesion and basement membrane alterations in experimental skin
      tumour development.
AB  - BACKGROUND: Epidermal cell adhesion and basement membrane (BM) are essential for
      the differentiated structure of squamous epithelium, and both are reduced in
      malignant tumours. MATERIALS AND METHODS: We analysed the expression of cell
      adhesion-related proteins desmoplakin and E-cadherin, BM components laminin and
      collagen IV, and BM receptor integrin alpha 6 in experimental preneoplastic
      changes and neoplasms of skin. Different mouse strains (NMRI, C57Bl/6 and DBA/2)
      and exposure protocols (DMBA, UV, DMBA + UV) were used to find possible
      differences in the expression of cell adhesion and BM proteins within individual
      tumour types. RESULTS: The individual strain had an impressive role on the
      expression of tumors. The exposure model affected the type of tumour found and
      tumour behaviour. The location and expression of cell attachment proteins were
      dependent on morphology, but mouse strain and type of exposure had no effect. The
      decline in the expression of markers studied was gradual involving the
      cytoplasmic immunoreactivity of integrin alpha 6 and laminin observed in
      dysplastic epidermis, BM structure formation becoming increasingly disturbed in
      dysplasia; this was present in squamous cell carcinomas and absent in
      undifferentiated tumours. Desmoplakin expression gradually disappeared during the
      decline in differentiation. E-cadherin expression was preserved longer, and
      disappeared along with the loss of squamous properties. CONCLUSIONS: Desmoplakin
      and E-cadherin served in this study as differentiation markers. None of these
      proteins seem to explain the differences in the tumour sensitivity of individual
      mouse strains.

PMID- 9615736
TI  - Complete inhibition of spontaneous pulmonary metastasis of human lung carcinoma
      cell line EBC-1 by a neutrophil elastase inhibitor (ONO-5046.Na).
AB  - We previously reported that EBC-1, a non-small cell lung cancer (NSCLC) cell
      line, produces immunoreactive neutrophil elastase (NE). In the present study, we
      examined the effects of ONO-5046.Na, a specific NE inhibitor, on the in vivo
      growth and spontaneous pulmonary metastasis of EBC-1 transplanted into severe
      combined immunodeficiency (scid) mice. In control mice, EBC-1 tumors inoculated
      subcutaneously grew steadily throughout 8-week observation period. The daily
      intraperitoneal injection of ONO-5046.Na (50 mg/kg/day) from day 1 completely
      suppressed the tumor growth. When ONO-5046.Na treatment was initiated 14 days
      after EBC-1 inoculation, it also caused a significant delayed growth of this cell
      line. Furthermore, ONO-5046.Na treatment completely inhibits the appearance of
      metastatic foci in lung at 8 weeks not only when it was administered from day 1
      but also when treatment was initiated 14 days after tumor inoculation, when solid
      tumors started to grow. The weight of the mice treated with ONO-5046.Na was
      similar to that of the control mice at 8 weeks, and they appeared as healthy as
      the control mice during the treatment. These results indicated that a NE
      inhibitor, ONO-5046.Na, inhibited both primary and metastatic growth of NSCLC
      with no marked side effects.

PMID- 9615737
TI  - Apoptosis induction in human breast cancer MRK-nu-1 cells by a polyamine
      synthesis inhibitor, methylglyoxal bis(cyclopentylamidinohydrazone)(MGBCP).
AB  - We have investigated the antiproliferative effects of a polyamine synthesis
      inhibitor, methylglyoxal bis(cyclopentylamidinohydrazone) (MCBCP), on human
      breast cancer MRK-nu-1 cells. MGBCP inhibited tumor growth of MRK-nu-1 cells in a
      dose-dependent manner as the polyamine contents in the cells decreased. Moreover,
      morphological changes indicating blebbing and chromatin condensation were
      observed in the MGBCP-treated cells, and hypodiploid subpopulations containing
      apoptotic cells were clearly detected in the profile of flow cytometric analysis.
      The number of characteristic oligonucleosome-sized fragments also increased as
      the concentration of MGBCP increased. The apoptotic effects of MGBCP were
      partially prevented by the addition of exogenous spermine. The results presented
      here suggest that, in addition to reducing the growth rate, MGBCP can induce
      apoptotic cell death in MRK-nu-1 human breast cancer cells by the reduction of
      intracellular concentrations of polyamines.

PMID- 9615738
TI  - Radiation-induced apoptosis of human prostate cancer cells is independent of
      mutant p53 overexpression.
AB  - BACKGROUND: Previous studies have demonstrated that androgen-independent prostate
      cancer cancer cells undergo apoptosis in response to ionizing irradiation. The
      p53 protein controls cell cycle arrest and apoptosis by acting as a checkpoint
      control that halts the cell cycle in G1, while DNA damage is present. In this
      study the effect of overexpression of mutant p53 protein, on radiation-induced
      apoptotic cell death of human prostate cancer cells PC-3 was investigated.
      MATERIALS AND METHODS: PC-3 cells were transfected with the plasmid encoding the
      mutant p53 sequence, and the neomycin resistance gene. Selected transfectant
      clones, were characterized at the molecular level (gene integration, and level of
      mRNA and protein expression) and cloned transfectants expressing high levels of
      p53 protein were treated with increasing doses of ionizing irradiation. The
      cellular response to radiation was determined on the basis of: a) clonogenic
      survival (colony forming ability of irradiated cells); b) induction of apoptosis
      as determined by the terminal transferase assay; c) apoptotic DNA fragmentation;
      and d) induction of expression of genes associated with prostate-apoptosis.
      RESULTS: Both mutant p53 transfectant and parental PC-3 cells underwent apoptosis
      in response to ionizing irradiation following similar kinetics of induction of
      DNA fragmentation. In addition, the magnitude of induction of expression of
      prostate apoptosis associated genes, SGP-2 and TGF-beta, was similar in the
      mutant p53 overexpressing and parental PC-3 cells and coincidental with DNA
      fragmentation. CONCLUSIONS: These findings seriously challenge the involvement of
      p53 in radiation-induced apoptosis in human prostate cancer cells and suggest
      that p53 mutations provide no selective advantage in the development of
      radioresistance of prostate tumor cells within the context of p53 independent
      apoptotic pathway.

PMID- 9615739
TI  - Intrahepatic lymphocyte analyses and assessment of the effects of levamisole in
      murine hepatic metastasis model.
AB  - We used hepatic metastasis models to determine the mechanism and effect of
      levamisole. BALB/c mice and Colon 26 cells were used. Group I was injected with
      tumor cells through the portal vein. Group II was primed with tumor cells before
      tumor cells injecting. Group III was same as Group II, but treated with
      levamisole. Surface antigens of intrahepatic lymphocytes and spleen cells were
      determined by FACScan with Anti-CD3, anti-CD4, anti-CD8, anti-CD45, anti-NK1.1
      and anti-F4/80. Nodules on the liver were greatest in Group I and fewest in Group
      III. Concerning intrahepatic lymphocytes, Group II, when compared with Group I,
      had increases of CD3+, CD4+ and CD8+ cells, and decreases of CD45+ and NK1.1+
      cells. Group III when compared with Group II, showed increased CD8+ cells and
      decreased of NK1.1+ cells. Levamisole is considered to be effective in the
      prevention of liver metastasis and is suggeste to enhanced CD8+ cells.

PMID- 9615740
TI  - Node status in lower lip squamous cell carcinoma in relation to tumor size,
      histological variables and DNA ploidy.
AB  - We studied a consecutive series of 54 cases of lower lip squamous cell carcinoma
      (LLSCC) in order to identify any variables which might predict the development of
      lymph node metastases. The cases were divided into 38 tumors without metastases
      (group I) and 16 tumors with lymph node metastases (group II). The following
      variables were investigated: tumor size, histologic grading, tumor maximal
      thickness, perineural infiltration and DNA ploidy, in a group of patients
      undergoing surgical treatment for LLSCC, and to show which of these might be
      predictive of the development of lymph node metastases.

PMID- 9615741
TI  - Influence of extracellular ion concentration on the intracellular accumulation of
      adriamycin.
AB  - The cytotoxic action of adriamycin is influenced by its intracellular
      accumulation. Therefore, it is important to clarify the mechanisms of adriamycin
      influx and efflux. In the present study, the influence of the extracellular KCl
      and Ca2+ concentration, the extracellular pH and the presence of NaHC03 on the
      ADR accumulation was investigated in order to study the mechanisms in ADR
      accumulation influenced by ions. The extracellular KCl concentration did not
      affect the intracellular ADR accumulation. This suggests the cell membrane
      potential does not affect the ADR accumulation since it is influenced by the KCl
      concentration. The intracellular intensity of fluorescence of Fluo3, an indicator
      of Ca2+, increased between 0 and 20 mM of the extracellular concentration of Ca2+
      ion. However, the ADR accumulation did not change between 0 and 20 mM of the
      extracellular concentration of Ca2+. This indicates that the extracellular
      concentration of Ca2+ does not affect the ADR accumulation under physiological
      conditions since 20 mM of Ca2+ is beyond normal physiological conditions.
      Further, the intracellular fluorescence of Fluo3 decreased as increasing the
      extracellular pH. In contrast, the ADR accumulation increased as increasing the
      extracellular pH. These suggest that the ADR accumulation increases as decreasing
      the intracellular Ca2+ as changing the extracellular pH. In wild type strain, the
      ADR accumulation did not change by the extracellular pH in the absence of NaHCO3,
      but increased as increasing the extracellular pH in the presence of NaHCO3. This
      suggests that the ADR accumulation in the wild type strain is influenced by
      NaHCO3 but the extracellular pH. In the ADR-resistant strain, the ADR
      accumulation decreased as increasing the extracellular pH regardless of NaHCO3.
      However, the accumulation of ADR increased as increasing the extracellular pH
      when the adjustment of pH was carried out with 1N HCl. This suggests that Cl- may
      play an important role in the ADR influx in the ADR-resistant strain.

PMID- 9615742
TI  - Nm23: an invasion suppressor gene in CNS tumours?
AB  - The nm23 gene family is widely documented as a suppressor of the metastatic
      phenotype in many human cancers. However, its role with respect to the invasive
      behavior of primary central nervous system tumours has scarcely been addressed.
      This review describes the members of this family identified to date and outlines
      the in vitro and in vivo data gathered from nearly ten years of nm23 research
      within the context of malignant progression in peripheral tumours. It is clear
      that this is an area which can no longer be ignored by the brain tumor community.
      Human nm23 bears strong sequence homology to the awd gene in Drosophila,
      mutations in which cause abnormal morphology of larval neural tissue. The
      functions and possible mechanisms underlying the ability of nm23 to suppress
      metastatic behavior are discussed.

PMID- 9615743
TI  - Cisplatin-resistant human small cell lung cancer cell line shows collateral
      sensitivity to vinca alkaloids.
AB  - A cisplatin-resistant cell line, SBC-3/CDDP, was established from a human small
      cell lung cancer cell line, SBC-3. The SBC-3/CDDP cells were 13.1-fold more
      resistant to cisplatin than the parent SBC-3 cells. We investigated the cellular
      changes of this cell line with regard to the development of resistance to
      cisplatin. The SBC-3/CDDP cells showed various characteristics as follows: a)
      increased intracellular glutathione and glutathione S-transferase content b)
      decreased intracellular accumulation of cisplatin, c) increased topoisomerase I
      activity and the same topoisomerase II activity as the parent SBC-3 cells, and 4)
      strong cross-resistance to the platinum analogues and mitomycin C, moderate cross
      resistance to 7-ethyl-10-hydroxy-camptothecin (SN-38), 4-hydroperoxy
      cyclophosphamide, etoposide, Adriamycin and methotrexate, and collateral
      sensitivity to vinca alkaloids and 5-fluorouracil. From these observations, the
      SBC-3/CDDP cells could be useful as a well characterized cisplatin-resistant cell
      line, and the resistance pattem in this cell line will give us much information
      for eradication of cisplatin-resistant tumor cells.

PMID- 9615744
TI  - Induction of apoptosis in MCF-7 breast carcinoma cell line by RAR and RXR
      selective retinoids.
AB  - Induction of apoptosis in MCF-7 breast carcinoma cell line by various retinoids
      was measured by cytofluorimetry and DNA fragmentation assay. Retinoids with
      marked or high selectivity for RAR alpha, RAR beta, RAR gamma or RXR alpha were
      tested. All these retinoids were capable of inducing apoptosis, in a dose- and
      time-dependent way. MCF-7 cell line expressed RAR alpha, RAR gamma and RXRs, but
      not RAR beta. Compared to untreated MCF-7 cells, after 2 days of incubation with
      each of the selective retinoids, a substantial increase in apoptotic cells was
      observed, even at the lowest concentration of 10(-8) M. Among the various
      analysed selective retinoids only slight differences were observed. All-trans
      retinoic acid and 13-cis retinoic acid induced apoptosis only after 6 days and 9
      cis-retinoic acid after 4 days of incubation. Since all receptor selective
      retinoids substantially inducedapoptosis, it may be concluded that RAR alpha, RAR
      gamma and RXR alpha are able to mediate programmed cell death in the tested tumor
      cell line. Highly selective retinoid receptor agonists and antagonists may be
      useful for clarifying the function of retinoid receptors and for further progress
      in the field of cancer prevention and therapy by retinoids.

PMID- 9615745
TI  - 5-FU uptake in liver metastases after intravenous and intraperitoneal
      administration: an autoradiographic study in the rat.
AB  - AIM: To analyse 5-fluorouracil (5-FU) uptake in hepatic metastases and normal
      tissues after intravenous (i.v.), intraperitoneal (i.p.e.) and intraportal (IPO)
      administration. METHODS AND RESULTS: A total of 18 inbred rats with hepatic
      metastases were injected with 14C-labelled 5-FU either through the i.v. (n = 7),
      i.p.e (n = 7) or IPO (n = 4) route. Radioactivity was visualised
      autoradiographically and quantified by computer-based image analysis. After 20
      minutes, 10 i.v. injected tumours showed a higher amount of radioactivity (mean
      +/- SD) 23.8 +/- 7.8 than 6 i.p.e. injected (16.5 +/- 5.1, P = 0.06). At 2 hours,
      9 i.v. injected metastases contained more radioactivity (49.6 +/- 9.2) than 19
      i.p.e. injected tumours (28.2 + 11.3, P = 0.00003). After 24 hours, 2 i.p.e.
      injected tumours had higher radioactivity (mean 25.2) compared with 7 i.v.
      injected (7.6 +/- 4.1). IPO administration did not confer higher radioactivity at
      any time point. When the calculations were based on average metastatic
      radioactivity of individual rats, the difference between i.v. and i.p.e. injected
      rats was still present at 2 hours. CONCLUSION: These results indicate that early
      tumour 5-FU uptake after intraperitoneal and intraportal administration may be
      inferior to that after intravenous injection. Deposition of the drug in the
      peritoneal cavity may, however, act as a slow release preparation giving
      continuous drug exposure for prolonged periods of time. These results suggest a
      role for combined intravenous and intraperitoneal adjuvant therapy.

PMID- 9615746
TI  - Cytotoxicity of ferratricarbadecaboranyl complexes in murine and human tissue
      cultured cell lines.
AB  - The ferratricarbadecaboranyl salts [1-(eta 5-C5H5)Fe-2-CH3-2,3,4-C3B7H9] + X-(X-
      = AsF6-, 1 and SbF6-, 2), as well as the neutral complex, 1-(eta 5-C5H5)Fe-2-CH3
      2,3,4-C3B7H9, 4, are effective cytotoxic agents, causing cell death in a number
      of tissue culture lines, e.g. L-1210, Tmolt3, HL-60, and HeLa-S3. In general,
      these agents were not active against the solid cell growth, i.e. KB nasopharynx,
      A431 skin, HCT-8 ileum, SW480 colon, osteosarcoma, and glioma. However, they were
      active against the growth of lung bronchogenic MB-9812. The mode of action of the
      derivatives involves inhibition of de novo purine synthesis of L-1210 cells,
      which reduces DNA and RNA syntheses. Purine synthesis was reduced by complexes [1
      (eta 5-C5H5)Fe-2-CH3-2,3,4-C3B7H9]+ [SbF6]- 2 and ?[1-(eta 5-C5H5)Fe-2-CH3-2,3,4
      C3B7H9]+ [SbF6]- [1-(eta 5-C5H5)Fe-4-CH3-2,3,4-C3B7H9]+ [SbF6]-? [20:1] 3, at the
      regulatory enzyme, i.e. PRPP amido transferase. The agents lowered d[ATP] and
      d[CTP] pools, further reducing DNA synthesis. The salts 1, 2, and 3 were shown to
      be moderate inhibitors of isolated L-1210 DNA topoisomerase activity. DNA strand
      scission was evident after incubation with compounds 1-4 and [1-(eta 5-C5H5)Fe-2
      CH3-2,3,4-C3B7H9 and 1-(eta 5-C5H5)Fe-4-CH3-2,3,4-C3B7H9] [20:1] 5, for 24 hours
      at 100 microM, lowering DNA synthesis, and causing cell death. The
      ferratricarbadecaboranes show activities and specificities different than those
      found for the analogous ferrocenium salts [(eta 5-C5H5)2Fe]+ [AsF6]- 6 and [(eta
      5-C5H5)2Fe]+ [SbF6]- 7, and the neutral ferrocene compound (eta 5-C5H5)2Fe 8. The
      bioactivites of both the tricarbaboranyl and metallocenium salts are attributed
      to the cations, since Na+[AsF6]- 9, K+ [AsF6]- 10, Na+[SbF6]- 11, and K+[SbF6]-
      12 were found to be inactive at equivalent ionic concentration.

PMID- 9615747
TI  - Change in chemosensitivity of DMBA-induced rat mammary tumor after oophorectomy.
AB  - BACKGROUND: A combination of chemotherapy and endocrine therapy is usually
      employed for the treatment of breast cancer, but the optimal order of this
      combination has not yet been verified. To determine the appropriate order of this
      combination, changes in chemosensitivity to anticancer agents after endocrine
      therapy were examined. MATERIALS AND METHODS: Rat mammary tumors induced by 7,12
      dimethylbenz[alpha]-anthracene (DMBA) were used. Chemosensitivity tests were
      performed before and 3 weeks after bilateral oophorectomy. The MTT assay was used
      to test eight anticancer agents, and oophorectomy was performed as the endocrine
      therapy. RESULTS: DMBA-induced rat mammary tumors showed sensitivity to 4'-0
      tetrahydropyranyl-doxorubicin, 5-fluorouracil, peplomycin, mitomycin C, and
      methotrexate. Chemosensitivity to these agents seemed to be somewhat reduced
      after oophorectomy compared with before the operation, but the difference was not
      significant. CONCLUSION: The influence of oophorectomy on chemosensitivity of
      DMBA-induced mammary tumor is thought to be minimal.

PMID- 9615748
TI  - Pirarubicin might partly circumvent the P-glycoprotein-mediated drug resistance
      of human breast cancer tissues.
AB  - BACKGROUND: Anthracyclines are the first line antitumor agents against breast
      cancer, and P-glycoprotein (Pgp) is thought to be the main resistance mechanism
      against these agents. We have evaluated the chemosensitivity of fresh surgical
      specimens of breast cancer and compared them with their Pgp-expression. MATERIALS
      AND METHODS: The in vitro chemosensitivity of 65 surgical specimens obtained from
      63 patients with advanced breast cancer was assessed by the histoculture drug
      response assay (HDRA) using doxorubicin (DXR), pirarubicin [(2"R)-4'
      tetrahydropyranyladriamycin: THP], and epirubicin (EPIR). Breast cancer tissues
      were plated onto collagen gel matrix and incubated with 15 micrograms of DXR or
      EPIR, or 17 micrograms of THP per ml for 7 days with MTT assessed at the
      endpoint. The efficacy of the agents was evaluated by the inhibition index (I.I.)
      of the optical density detected by ELISA reader. RESULTS: When 60% or more I.I.
      was regarded as in vitro sensitive at each cut-off concentration of the drugs,
      the overall efficacy rates were 60.7%, 48.6%, and 78.6% for DXR, EPIR, and THP,
      respectively. Fifty-one surgical specimens were evaluated for the
      immunohistochemical analysis of Pgp and the correlation between the sensitivity
      to anthracyclines and the expression of Pgp was compared. Pgp was expressed in
      23.5% (12/51) specimens and the efficacy of anthracyclines was reduced in Pgp
      positive breast cancer tissues, although this reduction was low in THP with a
      statistically significant difference when comparing with DXR and EPIR.
      CONCLUSION: The present results suggest that THP might partly circumvent the
      mdr1/PgP-mediated drug resistance mechanism in human breast cancer tissue and
      would have some different antitumor spectra on breast cancer comparing with DXR
      and EPIR.

PMID- 9615749
TI  - Vascular endothelial growth factor expression is reduced in liver metastasis from
      colorectal cancer and correlates with urokinase-type plasminogen activator.
AB  - We undertook a retrospective study to investigate the correlation between the
      expression of vascular endothelial growth factor (VEGF) and urokinase-type
      plasminogen activator (u-PA) proteins with progression of colorectal carcinoma
      (CRC). Immunohistochemical analyses using antibodies against VEGF and u-PA were
      carried out on archival specimens of 58 human colon carcinomas, 30 liver
      secondaries and 20 adenomas. Expression of VEGF was significantly reduced in the
      metastatic liver tumours compared with primary ones (Wilcoxon test, P = 0.002),
      suggesting VEGF activity to be secondarily down-regulated once the tumour cells
      reach the hepatic parenchyma. There was no strong evidence from our data that the
      level of VEGF or u-PA in the primary tumour could predict risk of liver
      metastasis or survival duration. VEGF and u-PA expression were positively
      correlated in primary CRC suggesting that both proteins may interact in vivo (chi
      square test, P = 0.019) in tumour progression.

PMID- 9615750
TI  - Determination of serum levels of 2,6 diethylaniline in laboratory animal treated
      with Alachlor.
AB  - In order to estimate the environmental risk of the use of Alachlor, experiments
      on laboratory animals were conducted. Alachlor and 2,6 diethylaniline content in
      blood serum was quantified. Three groups of male ACI/T rats and C3H/FEJ mice were
      treated with three different doses of Alachlor. Six hours after the
      intraperitoneal injection the animals were bled and blood was collected by
      cardiac puncture. From serum obtained after blood centrifugation, A and DEA were
      extracted using diethyl ether. 2,6 diethylaniline and Alachlor determinations
      were carried out by high performance liquid chromatography (HPLC). The HPLC
      revealed that the metabolic capacity of 2,6 diethylaniline production from
      Alachlor in rats is dose-dependent; moreover, the animals can be subdivided into
      at least two groups, according to their Alachlor metabolic capacities. In mice
      the metabolic release of 2,6 diethylaniline was found to be practically complete
      at every dose tested.

PMID- 9615751
TI  - Multiple forms of endonuclease activity linked with radiation induced apoptosis
      in C4-1 cervical carcinoma cells.
AB  - Irradiation of C4-1 cervical carcinoma cells induced apoptosis, as determined by
      their morphology and the presence of oligonucleosomal DNA fragmentation, with the
      formation of 5'- P and 3'-OH termini. Extracts of nuclear proteins from both
      control and irradiated cells possessed similar metallodependent endonucleolytic
      activity which cleaved target plasmid DNA with the same specificity as that found
      in apoptotic cells. Fractionation of the nuclear extracts revealed that the
      predominant endonuclease activity of unirradiated cells was a protein of
      approximately 40 kDa. After irradiation, the predominant activity was found to be
      associated with a 70 kDa fraction, with a reduction in the 40 kDa form. The
      activity of each endonuclease was found to be Ca2+ and Mg2+ dependent. It is
      proposed that the changes in molecular weight observed for these enzymes may be
      linked to the final step in apoptosis execution, irreversible chromatin
      fragmentation, and thus offer a potentially novel target for manipulating the
      effector pathway of apoptosis in these cells.

PMID- 9615752
TI  - Genetic instability, p53 and nm23 mutation and clinicopathological features in
      rectal carcinoma.
AB  - Defective DNA mismatch repair proteins fail to correct replication errors (RERs).
      These defects may lead to secondary, mutation of oncogenes and tumor suppressor
      genes. Microsatellite instability might be a marker of such replication errors.
      Eighteen rectal tumors were examined to evaluate genetic instability, in sporadic
      rectal cancer by PCR. RERs were observed in 27.8% of the cases. No significant
      difference was noticed between RER+ and RER- patients as far as prognosis,
      clinicopathological features and p53 gene mutation are concerned. The incidence
      of nm23 gene mutation was the only statistically significant difference between
      the 2 groups. Three patients with only one altered microsatellite showed advanced
      tumor and nm23 gene mutation. Two cases with 5 altered microsatellites and nm23
      gene mutated are disease-free: in one of them the p53 gene was also mutated.
      Probably more than one altered microsatellite is necessary to protect from the
      effects of secondary mutations.

PMID- 9615753
TI  - Hexadecylphosphocholine inhibits invasion of mouse T-cell lymphoma cells in two
      different invasion assays.
AB  - Hexadecylphosphocholine (HePC), an ether lipid analogue, is a new antineoplastic
      drug which has been shown to exert a remarkable antiproliferative effect in vitro
      and in vivo. The signal transduction pathway and the phospholipid synthesis are
      thought to be the main putative molecular targets of HePC, yet the exact
      mechanism of action is still unclear. To investigate the antiinvasive activity of
      HePC on a mouse T-cell lymphoma cell line (BW-O-Li1), we used a type I collagen
      gel and devitalized dermis as substrate to evaluate the migration of BW-O-Li1
      after exposure to HePC. BW-O-Li1 cells were exposed for 24 h to a non-cytotoxic
      (10 microM) as well as to cytotoxic concentrations of HePC. Afterwards, BW-O-Li1
      cells were seeded on top of a reconstituted collagen gel layer or pippeted into a
      steel ring placed on the dermal site of a devitalized dermis. Lymphoma cells,
      which invaded the collagen layer were counted by light microscopy, invasion into
      devitalized dermis was measured by an image analysis system. Compared to
      unexposed cells, invasion into the collagen gel differed significantly even at 10
      microM HePC, whereas the absolute number of invading cells, independently of the
      HePC concentration, showed no difference in the amount of counted cells.
      Migration into devitalized dermis was significantly reduced for 10 microM and 40
      microM HePC. These data show that complementary information can be obtained by
      application of the two invasion assays and that the antiinvasive effect of HePC
      emerges at non-cytotoxic concentrations of the substance.

PMID- 9615754
TI  - Electroporation therapy of human larynx tumors HEp-2 implanted in nude mice.
AB  - BACKGROUND: Electroporation therapy (EPT) uses reversible membrane
      permeabilization of cells by electrical pulses for intracellular delivery of
      poorly permeating drugs like bleomycin. This treatment modality has been found to
      significantly increase the cytotoxic effect of the drug to tumor cells. METHODS:
      Tumors of human epidermoid carcinoma of larynx (HEp-2) were xenografted
      subcutaneously in nude mice. EPT consisted of intratumoral injection of belomycin
      followed by 6 x 100 microseconds square wave electrical pulses of 1130 Volts. The
      effect of treatment on tumor growth was monitored over a period of 67 days.
      RESULTS: Complete regression of the tumors was observed in 83% of the treated
      mice 67 days after treatment. These findings were confirmed by histopathological
      analysis of tumor samples from the treated sites, which showed complete absence
      of tumor cells. CONCLUSIONS: The results indicate that electroporation therapy is
      very effective and has potential for treating laryngeal tumors clinically.

PMID- 9615755
TI  - Chromosome mediated gene transfer of drug resistance to mitoxantrone.
AB  - The anthracenedione, mitoxantrone, frequently selects for a unique drug
      resistance phenotype that is not mediated by either MDR 1, MRP, or altered DNA
      topoisomerase II. In this study, we demonstrate that mitoxantrone resistance is
      likely to be multifactorial with at least one resistance mechanism being the
      result of a dominant genetic event. This finding was demonstrated by conducting
      chromosome transfer experiments from human breast cancer cell lines that were
      either sensitive (MCF7/S) or resistant to mitoxantrone (MCF7/Mitox). Chromosomes
      transferred from MCF7/Mitox cells into CHO-K1 cells resulted in the isolation of
      multiple clones resistant to mitoxantrone. In contrast, chromosomes transferred
      from the drug sensitive MCF7/S, parent cell line did not confer drug resistance
      in the rodent CHO-K1 recipient cell line. Both Alu-PCR analysis and Southern blot
      analysis demonstrated human DNA in the CHO-K1 cells receiving chromosomes from
      the MCF7/Mitox cells. Unlike the MCF7/Mitox cell line, the drug resistant, CHO-K1
      chromosome transferrant clones did not have a decrease in total drug
      accumulation. We conclude that chromosome transfer from the MCF7/Mitox cell line
      into CHO-K1 cells, confers a non-transport mediated mechanism of drug resistance
      that is a dominant genetic event. These studies provide evidence of the genetic
      multifactorial nature of multidrug resistance in cells selected with mitoxantrone
      in-vitro.

PMID- 9615756
TI  - Efficiency of treatment with galactoside-specific lectin from mistletoe against
      rat glioma.
AB  - The cytotoxic activity of the galactoside-specific lectin from mistletoe
      (mistletoe lectin-1, ML-1) towards the anaplastic glioma cell line (F98) was
      investigated in vitro (three dimensional spheroid model) and in vivo (Fischer 344
      rats). Both model systems demonstrated the dose dependent cytotoxicity of ML-1.
      F98 glioma cell spheroid growth was significantly inhibited after incubation with
      defined ML-1 concentrations of 10 and 100 ng/mL. To investigate the in vivo
      efficacy Fischer 344 rats were intracerebrally implanted with F98 glioma cells
      and assigned to local and systemic ML-1 treatment, respectively. Histological and
      immunohistochemical evaluations proved a reduction of tumor volume for both
      treatment modalities, most pronounced and statistically significant after
      systemic (immunomodulating) administration of the optimal ML-1 dosage (1 ng/kg
      BW, subcutaneously) and after low dose (10 ng ML-1 per application (10 microL)
      local treatment. High dose ML-1 administration (10 ng/kg BW; systemically; 100
      ng/application, locally) was less effective than low (optimal) dose treatment and
      apparently the systemic/immunomodulating approach gained greater benefit for
      glioma bearing rats.

PMID- 9615757
TI  - Liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-MTP-PE): a
      randomized clinical trial in dogs with mammary carcinoma.
AB  - In this prospective randomized double-blind clinical study the anti-tumour
      activity of liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L
      MTP-PE) was evaluated as an adjuvant immunotherapy in dogs with mammary tumours
      of the simple carcinoma type. Dogs were randomized after surgery to one of two
      treatment groups, in which they were treated with either L-MTP-PE (2 mg/m2 i.v.;
      Ciba Geigy Basel, Switzerland) twice weekly for eight weeks, or with empty
      liposomes according to the same protocol. The minimal follow-up period was one
      year. Thirteen dogs were entered in the L-MTP-PE group and fourteen dogs in the
      placebo control group. Only minor toxicities (fever and shivering during 10-24
      hours) were seen in six dogs treated with L-MTP-PE, these being mainly of the
      smaller breeds. At the time of evaluation seven dogs were still disease free. In
      the other twenty dogs the disease-free period (DFP) was ended by local
      recurrences in 16 and by distant metastases in 4. The difference in DFP between
      dogs treated with L-MTP-PE (median 165 days, range 15-905) and dogs in the
      placebo group (median 133 days, range 27-659) was not significant. The difference
      in overall survival between the dogs treated with L-MTP-PE (median 222 days,
      range 36-905) and those receiving the placebo (median 182 days, range 54-659) was
      also not significant. It was concluded that liposome-encapsulated MTP-PE was not
      efficacious in the treatment of dogs with mammary carcinoma.

PMID- 9615758
TI  - Dolastatin 15 induces apoptosis and BCL-2 phosphorylation in small cell lung
      cancer cell lines.
AB  - BACKGROUND: The dolastatins are natural peptides which inhibit microtubule
      assembly and induce apoptosis in a number of malignant cell types. In small cell
      lung cancer (SCLC), bcl-2 overexpression is very common and appears to be a
      mediator of cell growth and treatment-resistance, suggesting that bcl-2 is a
      rational target for novel anti-SCLC strategies. Since several other tubulin
      binding agents have been reported to induce apoptosis in association with
      phosphorylation and inactivation of bcl-2, we evaluated the effects of dolastatin
      10 and 15 in SCLC cells. METHODS: The growth inhibitory activity of dolastatin 10
      and 15 was evaluated in four SCLC cell lines with an MTT assay. Cell cycle and
      the induction of apoptosis were evaluated by flow cytometry and fluorescent
      microscopy. Immunoblot analysis was used to determine bcl-2 expression and
      phosphorylation. RESULTS: Dolastatin 15 displayed growth inhibitory activity
      against all four SCLC cell lines (NCI-H69, NCI-H82, NCI-H345, NCI-H446) with IC50
      values ranging from 0.039-28.8 nM, which were 2.7-9.2-fold higher than the values
      for dolastatin 10. All four SCLC cell lines underwent G2/M arrest within 24 hours
      of exposure to dolastatin 15, and three had morphologic evidence of apoptosis
      after 48 hours. Immunoblot analysis of dolastatin 15-treated cells which
      overexpressed bcl-2 revealed a pattern consistent with bcl-2 phosphorylation.
      CONCLUSION: Dolastatin 15 has in vitro activity against SCLC cells, but is less
      potent than dolastatin 10. This activity is associated with the induction of
      apoptosis and bcl-2 phosphorylation. These findings suggest that further
      evaluation of the activity of the dolastatins in SCLC is reasonable and that the
      pharmacologic modulation of apoptotic pathways deserves further study as a
      potential anticancer strategy.

PMID- 9615759
TI  - Combined effects of TNP-470 and taxol in human non-small cell lung cancer cell
      lines.
AB  - The effects of TNP-470, one of the promising antiangiogenic agents and taxol when
      combined were evaluated in two human cultured cell lines derived from non-small
      cell lung cancer(NSCLC). Cytotoxicity was determined using a tetrazolium
      salt(MTT) assay. The inhibitory effects of TNP-470 on cell proliferation were
      dose related and the 50% inhibitory concentration on these cell lines were 50.0
      to 62.5 microM. Evaluation of drug interactions with isobologram and the
      combination index values showed that sequential exposure to taxol followed by TNP
      470 produced synergistic effects in these cell lines tested. Our findings suggest
      that such an angiocytotoxic chemotherapy might be promising for the treatment of
      NSCLC.

PMID- 9615760
TI  - High frequency of LOH at chromosome 18q in human breast cancer: association with
      high S-phase fraction and low progesterone receptor content.
AB  - Human primary breast cancers were analysed for somatic loss of heterozygosity
      (LOH) at chromosome 18 with 15 polymorphic microsatellite markers. LOH was
      observed in 148 of the 228 cases analyzed, (65%). Three smallest common deletion
      regions (SCDR) were detected on the long arm of chromosome 18. The marker D18S51
      at the region 18q22 showed the highest LOH (42%). Tumors with and without LOH at
      18q were tested for association with clinico-pathological features of the tumors,
      such as estrogen and progesterone receptor content, age at diagnosis, tumor size,
      node status, histological type, S-phase fraction, DNA ploidy and LOH at other
      chromosomal regions. A significant association was found between LOH at 18q and
      high S-phase fraction (99.9% confidence interval) and low progesterone receptor
      content (99% confidence interval). Furthermore, an association was found between
      LOH at 18q and LOH at 1p, 7q, 9p, 13q and 17q. We conclude that there are three
      separate LOH target regions at chromosome 18q, and that inactivation of one or
      more genes at these regions might be important for human breast carcinogenesis.

PMID- 9615761
TI  - Toxicity on human hemopoietic progenitors of 2'-2'-difluoro-2'deoxycytidine
      (gemcitabine).
AB  - This study presents results on 2'-2'-difluoro-2'deoxycytidine's (dFdC:
      gemcitabine) in vitro toxicity on peripheral blood CFU-GM and BFU-E obtained from
      healthy volunteers. Peripheral blood mononucleated non-adherent cells were
      cultured according to standard methods with continuous exposure (13 days) to dFdC
      (4,40 and 400 pmol/L) or following 1 hour's, incubation with increasing drug
      concentrations (1, 10, 100 mumol/L). The results indicate that dFdC has a marked
      dose-dependent inhibitory effect on the in vitro growth of peripheral blood
      hemopoietic progenitors., No significant differences were observed for the growth
      inhibition induced on CFU-GM and BFU-E. Continuous exposure to dFdC gave an IC50
      of 4 pmol/L for both CFU-GM and BFU-E. In four chemotherapy naive patients
      affected by tumors of different type treated with three standard courses of dFdC
      the variations in the peripheral blood of hemopoietic progenitor level were
      determined. Patterns of changes were different, but a marked and sustained
      decrease of both CFU-GM and BFU-E was observed in one case only. The contrast
      between the apparently rather mild clinical hemotoxicity of dFdC and its in vitro
      dramatically potent inhibitory activity on hemopoietic progenitors is discussed.

PMID- 9615762
TI  - Lung cancer cell line producing cytokeratin 19 fragment and sialyl Lewis X-i
      antigen.
AB  - A new human lung large cell carcinoma cell line producing cytokeratin 19
      fragment(CYFRA) and sialyl Lewis X-i antigen(SLX), designated TKB-13, was
      established from a patent in our laboratory. The cell line grew in a monolayer
      and had a polygonal epitheloid appearance in phase-contrast microscopy. The
      doubling time of TKB-13 cells was approximately 32 hours in Dulbecco's minimal
      essential medium with 5% fetal bovine serum. TKB-13 cells could be transplanted
      to nude mice and the histological characteristics were the same as those of
      resected tissue from the primary site. Positive reactions for CYFRA and for SLX
      were seen within the cytoplasm of TKB-13 cells by immunocytochemical staining.
      Both CYFRA and SLX were detected in the culture supernatant. Our results
      suggested that TKB-13 cell line is available for experimental studies on the
      biological behavior of non-small cell lung cancer.

PMID- 9615764
TI  - Effects of the lignan, arctiin, on 17-beta ethinyl estradiol promotion of
      preneoplastic liver cell foci development in rats.
AB  - Anti-promotional effects of arctiin, a lignan with antiestrogenic action, against
      17-beta ethinyl estradiol (EE) and 2-acetylaminofluorene (2-AAF) were examined
      using a medium-term liver bioassay based upon the induction of glutathione S
      transferase placental form (GST-P) positive foci in rat liver. Male F344 rats
      were initially injected with diethylnitrosamine (DEN, 200 mg/kg body weight)
      intraperitoneally and two weeks later were treated with arctiin (1%), EE (1.5 ppm
      or 5 ppm), 2-AAF (20 ppm), arctiin + EE (1.5 ppm or 5 ppm), or arctiin + 2-AAF
      (20 ppm) in the diet for 6 weeks and then killed, all rats being subjected to
      partial hepatectomy at week 3. EE and 2-AAF clearly increased the development of
      GST-P foci. Antipromotional effects of arctiin were observed only for 2-AAF.
      These findings provide experimental evidence that arctiin exerts weak-protective
      potential against hepatocarcinogenesis in rats.

PMID- 9615763
TI  - MKT-077, localized lipophilic cation: antitumor activity against human tumor
      xenografts serially transplanted into nude mice.
AB  - BACKGROUND: In in vitro experiments, the localized lipophilic cation, MKT-077,
      demonstrated time- and concentration-dependent antitumor activity. In the present
      experiment, the in vivo antitumor activity of MKT-077 was evaluated using human
      tumor xenografts serially transplanted into nude mice. MATERIALS AND METHODS: The
      antitumor efficacy of MKT-077 against five xenografts inoculated subcutaneously
      into nude mice was studied. Treatment with MKT-077 was initiated when the tumors
      started exponential growth. The antitumor activity of MKT-077 was assessed by a)
      the lowest value of the relative mean tumor weight of the treated:control tumors
      (T/CRW), where relative weight (RW) represented the change from baseline weight;
      and by b) the unadjusted weight of treated tumors at the end of the experiment.
      RESULTS: When MKT-077 was administered continuously using the Osmotic Micropump,
      antitumor activity was positively correlated with exposure time and drug
      concentration from 7.5 to 40 mg/kg/day. The maximum tolerated dose was 20
      mg/kg/day for 7 days. Co-4 (human colon cancer), St-4 (human gastric cancer), and
      CRL1420 (human pancreatic cancer) were evaluated as sensitive to MKT-077 in
      tested 5 strains. CONCLUSION: The antitumor activity of MKT-077 was confirmed
      using human tumor xenografts in nude mice.

PMID- 9615765
TI  - Chemosensitivity of human pancreatic cancer cell lines serially transplanted in
      nude mouse.
AB  - BACKGROUND: Pancreatic cancer frequently recurs or metastasizes even after
      apparently curative surgical resection. Because of a low, five-year survival rate
      after radical surgery, multi-modal adjuvant treatment must be used to prevent
      recurrence of systemic spread. MATERIALS AND METHODS: The effectiveness of the
      experimental cancer chemotherapy of mitomycin C (MMC), cisplatin (DDP),
      doxorubicin (DXR) and 5-fluorouracil (5-FU) was evaluated in three human
      pancreatic cancer xenografts serially transplanted in nude mice. RESULTS: When
      the effects of these agents were evaluated by 3-(4,5-dimethylthiazol-2yl)-2,5
      diphenyl-2H tetrazolium bromide (MTT) assay, only MMC and DDP were effective on
      PAN-3-JCK, a poorly differentiated adenocarcinoma. When PAN-12-JCK, a moderately
      differentiated adenocarcinoma, was used an in vitro assessment of combined
      chemotherapy of MMC and DDP, a synergistic combination effect was observed. Three
      xenografts were transplanted subcutaneously into nude mice and the maximum
      tolerated doses of these agents were administered intraperitoneally or
      intravenously (DXR). MMC showed positive antitumor activity on PAN-3-JCK and PAN
      12-JCK, and 5-FU was effective on PAN-12-JCK. CONCLUSIONS: These results reflect
      the low sensitivity of clinical pancreatic cancer to conventionally available
      antitumor agents, and suggest the possible synergistic combination antitumor
      activity of MMC and DDP.

PMID- 9615766
TI  - Mammary epithelium-induced motility of MCF-7 cells.
AB  - BACKGROUND: Cancer cell invasion may be mediated by motility factors elaborated
      by the surrounding normal host tissue. This study was performed to determine
      whether normal breast cells induce motility in breast cancer. MATERIALS AND
      METHODS: MCF-7 breast carcinoma cells were co-cultured with either normal
      cultured human mammary epithelial cells (HMEC) or immortalized 184 A1 mammary
      epithelial cells and observed for evidence of motility. The ability of
      conditioned medium from mammary epithelial cells to induce motility in MCF-7 was
      measured with scattering assays, Boyden chamber assays and time-lapse video
      microscopy. RESULTS: A soluble factor in the conditioned medium of both 184 A1
      and HMEC induced motility in MCF-7. The motility factor was trypsin-sensitive,
      but activity remained after 5 minutes of boiling or 2 hours at pH 2. CONCLUSION:
      Mammary epithelium secretes a protein capable of inducing motility in breast
      cancer cells, raising the possibility that this effect contributes to the
      invasive properties of human mammary carcinoma.

PMID- 9615767
TI  - Relationship between radical intensity and cytotoxic activity of dopamine-related
      compounds.
AB  - Millimolar concentrations of dopamine (DA), norepinephrine (NE), and 3,4
      dihydroxyphenylacetic acid (DOPAC) were cytotoxic to human promyelocytic leukemiC
      HL-60 cells. However, their metabolites (3,4-dihydroxymandelic acid (DOMA), 3
      methoxytyramine (MT), normetanephrine (NMN)) and six synthetic derivatives (which
      have two OCH3 groups replacing two OH groups on catechol backbone) displayed much
      lower cytotoxic activity. Three active compounds, but not other less potent
      compounds, produced radicals under alkaline conditions. All active compounds
      significantly enhanced the decay of ascorbic acid endogenously present in rat
      brain homogenate, whereas all synthetic derivatives were inactive. Ascorbic acid
      induced apoptotic cell death in HL-60 cells and the apoptosis induction was
      significantly reduced by simultaneous addition of (DA). The cytotoxic activity of
      (DA) was also neutralized by ascorbic acid. These data suggest the possible
      interaction between (DA) and ascorbic acid.

PMID- 9615768
TI  - Free radical erythrocyte damage in tumoral disease assessed by He-Ne laser and
      optical microscope through "Heinz Bodies" method.
AB  - Results obtained from blood sample readings by optical microscopy and He-Ne laser
      (lambda = 630.1 mW), have confirmed the reduction in Heinz Bodies (HB) formation
      time and the Transmittance Reduction Degree (TRD), in malignancies. The results
      of spectrometric readings in colorectum polyposis, (TRD = 0.07) and fibrocystic
      mastopathy (TRD = 0.08) gave results overlapping with controls (TRD = 0.08). In
      neoplasias, the early HB formation in erythrocytes observed by optical microscope
      corresponded to TRD increase = 0.17 (P < 0.01). TRD increase was statistically
      significant (P < 0.01), as well as the reduction in the time of HB appearance (<
      0.01). The relationship between optical and laser readings was exponential in
      tumors, while it was linear in controls, in polyposis and mastopathies. The
      values of the correlation coefficients obtained by both methods were significant
      (P < 0.01) for all the studied groups. Moreover, these research data further
      support the existence, even in the earlier stages of the disease, of the labile
      state of the red cell membrane due to strong lipid peroxidation by FRs.

PMID- 9615769
TI  - Role of thromboxane receptor on the intracellular accumulation of cis
      diamminedichloroplatinum(II) in non-small-cell but not in small-cell lung cancer
      cell lines.
AB  - cis-Diamminedichloroplatinum(II) (CDDP) is a key anticancer agent. It has been
      reported that intracellular accumulation of CDDP is an important step as a
      determinant for resistance to CDDP, which may be modulated by Na+, K(+)-ATPase
      activity. In this study, the significance of membrane Na+, K(+)-ATPase activity
      and the role of thromboxane (TX) receptors were evaluated using human lung cancer
      cell lines. In the non-small-cell lung cancer (NSCLC) cell line, EBC-1,
      sensitivity to CDDP was improved by treatment with two different selective
      thromboxane receptor antagonists, calcium 5(z)-[1R,2S,3S,4S-7-[3
      phenylsulfonylaminobicyclo [2.2.1]hept-2-yl]-5-heptenoate hydrate (S-1452), and
      (3R)-3-(4-fluorophenyl sulfonamido)-1,2,3,4-tetrahydro-9-carbazolepropanoic acid
      (BAYu3405). Na+, K(+)-ATPase was activated and intracellular accumulation of CDDP
      increased with treatment in EBC-1. In the small-cell lung cancer (SCLC) cell
      lines, SBC-1, sensitivity to CDDP and Na+, K(+)-ATPase activity did not change
      significantly, and intracellular accumulation of CDDP was not modulated. These
      results suggest the importance of the TX receptors as determinants of the
      sensitivity to CDDP in NSCLC cell lines. However, Na+, K(+)-ATPase activity and
      the role of TX receptors may not be so significant in the resistance mechanisms
      to CDDP in SCLC cell lines. In EBC-1 cells, the specific binding of S-145 was
      evident, but not in SBC-1 cells. The difference in TX receptors in NSCLC and SCLC
      cell lines may be one of the reasons for the variety of the antitumor effects of
      CDDP in chemotherapy for lung cancer.

PMID- 9615770
TI  - Significance of Na+, K(+)-ATPase on intracellular accumulation of cis
      diamminedichloroplatinum(II) in human non-small-cell but not in small-cell lung
      cancer cell lines.
AB  - cis-Diamminedichloroplatinum(II) (CDDP) is the most active anticancer agent. It
      has been reported that intracellular accumulation of CDDP is an important step as
      a determinant for resistance to CDDP, which may be modulated by Na+, K(+)-ATPase
      activity. In this study, the significance of membrane Na+, K(+)-ATPase activity
      in the intracellular accumulation of CDDP were evaluated using human lung cancer
      cell lines. Na+, K(+)-ATPase was active in each cell line, not only non-small
      cell lung cancer (NSCLC) but also in small-cell lung cancer (SCLC) cell lines. In
      NSCLC cell lines, there were significant correlations between Na+, K(+)-ATPase
      activities and intracellular accumulation of CDDP and the accumulation
      significantly decreased by ouabain, an inhibitor of Na+, K(+)-ATPase in each cell
      line. However, the correlation between enzyme activity and intracellular
      accumulation of CDDP were not significant in SCLC cell lines where sensitivity to
      CDDP was better than in NSCLC cell lines. These results suggest Na+, K(+)-ATPase
      are active in both NSCLC and SCLC cells, however, the importance of the enzyme as
      an active transporter of CDDP may be limited only to NSCLC cells. The mechanisms
      of intracellular accumulation may not be so important as a determinant of
      sensitivity to CDDP in SCLC cells.

PMID- 9615771
TI  - Multiwavelength videomicrofluorometric study of some human leukemic lymphoblasts:
      effect of adriamycin on some biological parameter.
AB  - The development of multidrug resistance (MDR) in heterogeneous cell sensitive and
      resistant populations to a variety of clinically important cytotoxic drugs poses
      a major obstacle to cancer chemotherapy. The MDR phenotype is characterized by a
      decrease the intracellular drug accumulation and by an overexpression of the MDR1
      gene which encodes the membrane protein, P-glycoprotein (Pgp). To evaluate the
      MDR phenotype, rationale investigations of the cytotoxic processes and effect,s
      of Adriamycin (ADR) were done to obtain information on individual cells. Such
      information could be obtained through a multiparametric approach involving
      multiwavelength microfluorometry and numerical image analysis on single living
      cells. To achieve this, cells should be simultaneously stained with Hoechst 33342
      (nuclear staining), Rhodamine 123 (mitochondria staining) and Nile Red (cell
      contour delineation). Changes in the biological parameters accessible from R123,
      Ho33342 and C-SNARF-1/AM (probe used for the pHi measurements) labelling were
      found more informative than changes in morphological parameters for the
      discrimination of sensitive and resistant cells. Furthermore, this approach
      allows the discrimination between two resistant cell lines expressing different
      mechanisms of resistance.

PMID- 9615772
TI  - Effect of butyrate analogues on proliferation and differentiation in human
      neuroblastoma cell lines.
AB  - Butyric acid has been shown in vitro to produce cytodifferentiation of a wide
      variety of neoplastic cells. The potential clinical use of this compound as a
      therapeutic agent is limited by its rapid metabolism. This has led to the
      examination, as potential antineoplastic agents, of compounds structurally
      correlated to butyrate, with longer biological half lives. In this study we
      investigated the effect in vitro of two butyrate analogues, tributyrin and
      butyramide, on inducing growth inhibition and expression of morphological and
      immunophenotypic properties, in human neuroblastoma cell lines. Treatment with
      tributyrin resulted in a strong inhibition of cell proliferation and in induction
      of extensive differentiation; on the contrary butyramide was scarcely effective
      or quite ineffective. These results demonstrate that tributyrin retains the
      effectiveness of butyrate and suggest that this analogue could have utility for
      cytodifferentiation therapy.

PMID- 9615773
TI  - Species, strain and sex differences in susceptibility to gamma radiation combined
      with diethylnitrosamine.
AB  - Our previous data suggested that in Sprague-Dawley (SD) rats, a short-term in
      vivo radiation carcinogenesis model can be established using glutathione S
      transferase placental form (GST-P) positive hepatic foci induced by
      diethylnitrosamine (DEN) after gamma radiation. In the present study, differences
      between species, strain and sexes in susceptibility to radiation or radiation
      combined with DEN were examined. Newborn Fischer 344 (F344) and SD rats, and
      N:GP(S) mice were irradiated with whole body single 3Gy of gamma rays with or
      without intraperitoneally-injected DEN (15 mg/kg body weight) within 1 h of
      irradiation. Three weeks later, 0.05% phenobarbital was given in drinking water
      as a promoter, and at week 21 after birth, all animals were sacrificed. In both
      the radiation alone and radiation combined with DEN groups, F344 rats were more
      susceptible than SD rats to the induction of GST-P+ foci. In F344 rats, no
      significant difference in foci induction was seen between the sexes in both
      radiation alone and radiation combined with DEN groups, but in SD rats, female
      rats were more susceptible than males. In the case of mice, lung tumor incidence
      was examined, and in the radiation alone group, no differences between the sexes
      were seen; in the radiation combined with DEN group, however, females were more
      susceptible than males. These results suggested that susceptibility to radiation
      carcinogenesis could be potentiated by chemical carcinogens and showed wide
      variation between species, strains and sexes, of experimental animals.

PMID- 9615774
TI  - Apoptosis in prostatic adenocarcinomas; a study of relationship to Ki-67 and Bcl
      2 protein expression.
AB  - BACKGROUND: Tissue samples from patients with prostatic adenocarcinoma (PCA) were
      examined for relationship between apoptosis and expression of Ki-67 and bcl-2
      protein. MATERIALS AND METHODS: Prostatic tissue was obtained from 29 prostatic
      cancer patients with no prior therapy. The number of apoptotic cells (apoptotic
      index; AI) and the percentage of Ki-67 stained cells (Ki-67 labeling index; LI)
      were compared with the expression of bcl-2 which was evaluated by the proportion
      and intensity of tumor cell immunostaining. RESULTS: Both AI and LI of moderately
      and poorly differentiated PCAs were significantly higher than those of well
      differentiated PCAs. There was a significant correlation between AI and LI. Bcl-2
      protein was expressed less in moderately and poorly differentiated PCAs than in
      well differentiated PCAs. Moreover, there was no correlation between the bcl-2
      protein expression and the AI. CONCLUSIONS: The results suggest that, in PCAs,
      the degree of apoptosis is correlated with the cellular proliferation, and that
      expression of bcl-2 protein is not a critical factor that determines the degree
      of apoptosis.

PMID- 9615775
TI  - Bioflavonoids commonly and potently induce tyrosine
      dephosphorylation/inactivation of oncogenic proline-directed protein kinase FA in
      human prostate carcinoma cells.
AB  - In this study, we investigate the effect of bioflavonoids on the activity and
      phosphotyrosine content of oncogenic proline-directed protein kinase FA (PDPK FA)
      in human prostate carcinoma cells. Chronic treatment of human prostate carcinoma
      cells with low concentrations of quercetin, apigenin, and kaempferol commonly and
      potently induced tyrosine dephosphorylation and concurrent inactivated oncogenic
      PDPK FA in a concentration-dependent manner. This is demonstrated by a specific
      assay of this kinase's activity in the immunoprecipitates from the cell extracts
      followed by immunoblotting and phosphotyrosine analysis. The results indicate
      that bioflavonoids may function as common tyrosine kinase inhibitors to inhibit
      PDPK FA-specific tyrosine kinase and thereby to induce tyrosine
      dephosphorylation/inactivation of this oncogenic kinase in human carcinoma cells.
      Under this condition, quercetin, apigenin, and kaempferol can also inhibit cell
      growth in a similar concentration-dependent manner. The results further indicate
      that inhibition of tyrosine phosphorylation/activation of this oncogenic PDPK
      represents a new mode of action mechanism for bioflavonoids during the
      antiproliferation process in human carcinoma cells.

PMID- 9615776
TI  - Basic fibroblast growth factor and vascular endothelial growth factor in sera
      from non-small cell lung cancer patients.
AB  - BACKGROUND: The formation of new microvessels from the existing vascular bed is
      known as angiogenesis and is normally under the tight regulatory control of
      angiogenic factors. This control is lost in malignant tumours. Previous studies
      have correlated increased microvessel density with poor prognosis in patients
      with primary lung cancer. MATERIALS AND METHODS: Our group measured levels of
      vascular endothelial growth factor (VEGF) and basic fibroblast growth factor
      (bFGF) in sera from 68 patients with non-small cell lung cancer (NSCLC) and
      compared elevated levels of VEGF and bFGF with clinical outcome. Serum basic FGF
      and VEGF were measured using commercially available enzyme- linked immunosorbent
      assays (R & D Systems Inc., Minneapolis, MN USA). RESULTS: In 26/68 (38%)
      patients we found that elevated circulating levels of bFGF and in 27/68 (39%)
      serum samples levels of VEGF were elevated. Elevated bFGF values in sera was a
      statistically significant good prognostic factor, p- value = 0.048, when adjusted
      to stage and there was a trend in that patients with elevated levels of bFGF had
      a higher fraction of adenocarcinomas compared with squamous epithelial carcinomas
      (chi 2 = 2.0). No significant correlations could be demonstrated when elevated
      levels of VEGF in serum was present. Elevated levels of both VEGF and bFGF was
      present in 45% of the patients. CONCLUSIONS: We found that elevated levels of
      bFGF is a good prognostic factor when measured in sera from NSCLC patients. As
      this result disagrees with earlier studies on other malignancies the results from
      our study needs to be further investigated in a prospective study.

PMID- 9615777
TI  - The expression of C-myb in human metastatic melanoma cell lines and specimens.
AB  - The rapidly increasing incidence of malignant melanoma and lack of effective
      systemic therapy for advanced disease has given rise to the need for new
      approaches. The suggestion that c-myb may be an important gene in the control of
      melanoma proliferation prompted the exploration of its expression in several
      metastatic melanoma cell lines and specimens. Initial Northem hybridization
      showed undetectable expression of c-myb in the cell lines, although it was very
      strongly expressed in the K-562 cell line. Therefore, c-myb expression was
      examined utilizing primers and RT-PCR on the five melanoma cell lines and thirty
      two metastatic melanoma specimens. There was very low expression in the two cell
      lines (UISO Mel-1 and 3) that were nontumorigenic, whereas there was a 10 fold
      increase in expression in the tumorigenic cell lines. In the metastatic specimens
      the expression varied by over 100 fold between the lowest and highest specimens.
      The expression of c-myb in tumor specimens was in general greater than matched
      normal specimens, save for skin which had moderate expression. In general, there
      did not appear to be any correlation between the clinical characteristics of the
      various specimens and the amount of c-myb expression. However, females with lymph
      node metastases had somewhat lower expression than males. The fact that
      significant melanoma specimens have altered expression of c-myb, coupled with the
      previous inhibition of melanoma growth by antisense c-myb, suggests that there
      may be a potential role for c-myb antisense therapy in the treatment of this
      tumor.

PMID- 9615778
TI  - Antitumor effect of S-1 on DMH induced colon cancer in rats.
AB  - The aim of this study was to establish an autochthonous colon cancer model in the
      rat as an in vivo secondary screen for the general evaluation of new anticancer
      agents against colorectal cancer, and also to evaluate practically the antitumor
      activity of 1M tegafur-0.4M 5- chloro-2,4-dihydroxypyridine-1M potassium
      oxonate(S-1), a new p.o. fluoropyrimidine. Thirty-two Sprague-Dawley rats
      received dimethlhydrazine(40 mg/kg) s.c. once weekly for 10 weeks to induce colon
      cancer.20 weeks after beginning the carcinogen treatment, a barium enema was
      performed to visualize tumors. The animals were divided into a control group and
      S-1 treatment group. After 5 weeks of treatment, the barium enema was repeated.
      The mean doubling time of 24 tumors in the control group was 19.0 + 8.4 (SD)
      days. Response to S-1 was judged as effective when the doubling time exceeded
      35.8 days, calculated from the mean + 2SDs in the control group. The response
      rate of S-1 was 55%, 34% of the tumors were decreased in size after treatment.
      This figure was higher than that of clinically-used 5-fluorouracil(5-FU)
      derivatives; 5-FU;6%, Tegafur(FT):6%, 1M tegafur-4M uracil(UFT):14%, reported in
      our previous study. An autochthonous colon cancer model is useful to evaluate the
      clinical therapeutic efficacy of drugs for colorectal cancer, and S-1 is expected
      to have a high therapeutic effect on human colorectal cancer.

PMID- 9615779
TI  - Adenocarcinoma of the cecum with Crohn's-like features in baboons.
AB  - During the past 9.5 years, 51 baboons dying as a result of chronic diarrhea and
      poor health and having a chronic inflammatory process of the cecum (i.e.
      typhlitis) were recorded. The cecum was turgid, irregularly thickened the lumen
      reduced and the mesenteric lymph nodes enlarged. Of the 45 baboons with well
      preserved histologic material, 24 had shallow ulcerations and/or focal mucosal
      inflammation, 3 had crypt abcesses, 3 had mucosal fissures,l aphtoid ulcerations,
      and 1 pseudopyloric metaplasia (ulcer associated cell lineage-UACL-). The
      submucosa in all 45 animals was thick due to fibrosis, 35 had focal chronic
      inflammation with lymphoid aggregates, 12 submucosal abcesses, 6 epithelioid cell
      granulomas, 5 fissures reaching the submucosa, 3 neural hyperplasia of the
      myenteric plexus, and 2 lymphangiectasia. Focal chronic transmural inflammation
      with lymphoid aggregates was recorded in 44 animals. In addition, 2 animals
      showed deep fissure tracts. Ten of the 45 animals had in addition a cecal
      adenocarcinoma; one was overlayed by a villous adenoma with high grade dysplasia.
      Liver metastasis was found in another animal. The present study indicated that a)
      baboons may develop transmural chronic focal inflammation in the proximal colon
      (cecum), b) the inflammation in baboons closely mimic Crohn's disease of the
      cecum in humans c) adenocarcinomas in baboons with Crohn's-like inflammatory
      changes may originate in an adenomatous growth, and d) cecal adenocarcinomas in
      baboons with Crohn's-like inflammatory changes of the cecum, are able to
      metastasize.

PMID- 9615780
TI  - Effect of ABVD therapeutic protocol on oncogene and tumor suppressor gene
      expression in CBA/Ca mice.
AB  - The in vivo investigation of onco/suppressor gene effects may provide new
      information on chemical-environmental carcinogenesis. We previously described the
      elevation of onco/suppressor gene expression due to CHOP and COPP
      chemotherapeutical protocols in a CBA/Ca mouse model. Below we describe the
      results of the onco/suppressor gene expression studies after treatment with ABVD,
      a non-cyclophosphamide containing protocol. Expression of c-myc, Ha-ras, and p53
      genes was investigated 1/2, 1, 3, 6, 12, 24 hours, 2 6 30 days, 6, and 12 months
      after treatment with a single dose of ABVD protocol. RNA was isolated from the
      thymus, spleen, liver, bone marrow, kidneys, and hybridzed with
      chemiluminescently labelled probes of Ha-ras, c-myc, and p53 genes. Significant
      changes of gene expression was found in the spleen and thymus, even after 30
      minutes. The female spleen seemed to be more sensitive than the male one, but no
      sex difference was observed in the thymus. No significant alteration was detected
      in the other investigated organs.

PMID- 9615781
TI  - Expression of placental protein 14 by the new endometrial cancer cell line MFE
      280 in vitro and by endometrial carcinomas in vivo.
AB  - MFE-280 endometrial cancer cells express PP14 (placental protein 14) in vitro.
      PP14 is normally found in the secretory endometrium and in placental tissue. MFE
      280 cells, which are tumorigenic in nude mice, were derived from a recurrent,
      poorly differentiated endometrial carcinoma. The cells were initially grown in
      suspension culture and later transferred to monolayer cultures. Karyotyping
      revealed near-diploidy with a complex heterogeneous aberration pattern. MFE-280
      cells were positive for the cytokeratins 7, 8, 18 and 19 as well as for vimentin.
      The expression of PP14 in MFE-280 cells was demonstrated by immunochemistry and
      reverse transcriptase--polymerase chain reaction. PP14-mRNA was also detected in
      one out of five endometrial cancer specimen. In tumor tissue the expression of
      PP14 was not dependent on progestins.

PMID- 9615782
TI  - Cytoplasmic localization of anthracycline antitumor drugs conjugated with reduced
      glutathione: a possible correlation with multidrug resistance mechanisms.
AB  - The accumulation of adriamycin (ADR), daunomycin (DAUNO) and their glutathione
      (GSH)-conjugates, recently obtained by anaerobic reaction of the parent
      anthracyclines with reduced GSH, was examined in drug-sensitive and multidrug
      resistant (MDR) cell lines using confocal laser scanning microscopy. In all drug
      sensitive lines used (TVM-A12 and TVM-A197 human melanoma cells, K562
      lymphoblastoid cells and MCF-7 human breast cancer cells) ADR and DAUNO were
      mostly located in the nuclei, while their GSH-conjugates were found only in the
      cytoplasm, predominantly in the Golgi region. On the contrary, in MDR MCF-7/Dox
      cells, both conjugated and non conjugated anthracyclines gave fluorescence only
      in the cytoplasm, mostly in the Golgi region, the intensity of the fluorescence
      being stronger in cells pretreated with verapamil. Viability assay showed that
      the GSH-conjugate are significantly less cytotoxic than the parent anthracyclines
      in sensitive cells and showed the same scarce cytotoxicity in MDR MCF-7/Dox
      cells. These results demonstrate that conjugation of anthracycline antitumor
      drugs with GSH prevents their access to the nucleus and decreases their
      cytotoxicity. Furthermore, the observations on MCF-7/Dox suggest that GSH
      conjugation of anthracycline might occur in resistant cells and can be in part
      responsible for the MDR in breast cancer cells.

PMID- 9615783
TI  - Immunohistochemical detection of bcl2, p53, mdm2 and p21/waf1 proteins in small
      cell lung carcinomas.
AB  - Thirty-one cases of small cell lung carcinomas (SCLC) were investigated by
      immunohistochemistry for the expression of bcl-2, p53 and the wild-type (wt) p53-
      induced proteins mdm2 and p21/waf1. Bcl-2 protein was detected in 24/31 cases of
      SCLC(77%) and p53 protein in 13/31 cases (42%). No correlation was found between
      histological subtype of SCLC and bcl-2 or p53 expression. Comparison between bcl
      2 and p53 expression showed that 14/31 cases (45%) were only bcl-2 positive, 3/31
      (11%) were only p53 positive, 10/31 (32%) were positive for both proteins and
      4/31 (13%) were negative for both proteins. Mdm2 protein was detected in 2/32
      SCLC which were also p53 positive. P21 protein was detected in 6/32 SCLC. Four of
      the p21 positive SCLC were negative for both p53 and mdm2, and two were positive
      for both p53 and mdm2 proteins. The significant expression of bcl-2 protein in
      SCLC suggests that bcl-2 may be involved in the pathogenesis of most SCLC by
      inhibiting apoptosis during neoplastic transformation. The expression of p53
      protein in SCLC is likely to be related to underlying p53 gene mutations since
      these genetic alterations are very frequent in SCLC. This can be supported by our
      findings that 11/13 p53 positive SCLC were mdm2 and p21 negative. The two cases
      with p53+/mdm2+/p21+ phenotype may represent tumours with wt p53 gene and p53
      protein immunoexpression due to binding to mdm2 protein. The four cases with p53
      /mdm2-/p21+ phenotype may represent tumours with p53-independent p21 protein
      expression. Coexpression of p53 and bcl-2 proteins in a proportion of SCLC
      suggests that in these tumours p53 doses not maintain its suppressive effect on
      bcl-2 expression as it has been reported in vitro. Further studies at DNA and RNA
      level are required to clarify the involvement of bcl-2, p53, mdm2 and waf1 genes
      in SCLC pathogenesis.

PMID- 9615784
TI  - Copper/zinc superoxide dismutase expression by different human osteosarcoma cell
      lines.
AB  - Oxidative stress has been frequently implicated in the initiation and promotion
      phases of carcinogenesis. Antioxidant enzymes, which can antagonize this process,
      are lowered in a number of malignancies even though different findings have been
      reported in the literature. It has been shown that tumors have less copper/zinc
      superoxide dismutase (Cu/Zn SOD) in comparison with the more metabolically active
      tissues, but there is a large overlap between normal and tumor tissue. In order
      to examine the relationship between osteosarcoma at different degrees of
      proliferation and differentiation and Cu/Zn SOD levels, four different human
      ostosarcoma cell lines: HOS, U-2 OS, MG63, Saos-2 were studied for their
      production and release of Cu/Zn SOD. A normal human stromal cell line was used as
      control. Osteosarcoma cells were stimulated with TNF alpha, a cytokine previously
      shown to have antiproliferative activity. The release of Cu/Zn SOD into the
      supernatant was higher for the HOS and U-2 OS lines when compared to the other
      cell lines evaluated both in basal condition and after incubation with TNF alpha.
      Elevated intracellular levels of Cu/Zn SOD were shown except for the HOS and U-2
      OS which possess high concentrations of the enzyme at 24 hours declining during
      the other incubation periods. These concentrations were increased after TNF alpha
      treatment. The different behaviour of the four cell lines evaluated might be
      explained by their degree of differentiation.

PMID- 9615786
TI  - NM23-H1 and NM23-H2 gene expression in human renal tumors.
AB  - The two nm23 genes, nm23-H1 and nm23-H2, are implicated in the metastatic process
      and tumor progression in some human tumors. Until now no data exist about nm23
      expression in the different types of human renal tumors. To investigate if the
      nm23 genes play a central role in the progression of renal tumors, we have
      examined nm23-H1 and nm23-H2 gene expression using Northern-blot analysis and
      immunohistochemistry. We analysed clear cell type RCC, chromophilic RCC,
      chromophobic RCC, collecting duct type RCC and renal oncocytomas. Our results
      indicate that the nm23 genes do not play a central role in the prognosis of renal
      cell carcinoma in the analysed tumors.

PMID- 9615785
TI  - A comparative study on the photocytotoxicity of hypericin on A431 cells using
      three different assays.
AB  - BACKGROUND: Three assay models were adopted for assessing the photocytotoxicity
      of hypericin on A431 cells. The cells were incubated for 1 hour or 24 hours with
      hypericin to evaluate the importance of the incubation period on the exerted
      photocytotoxicity. MATERIALS AND METHODS: A neutral red, an antiproliferative and
      a tetrazolium-reduction (MTT) assay were used for the estimation of cytotoxicity.
      RESULTS: IC50 values were 296, 321 and > 500 nM after 1 hour, and to 70, 54 and
      277 nM after 24 hours, for the neutral red, antiproliferative and MTT assays,
      respectively. CONCLUSIONS: Our results clearly show that it is imperative to
      incubate cells for long periods to fully assess the hypericin photocytotoxicity,
      and that the neutral red assay is as sensitive as the antiproliferative assay but
      superior to the MTT assay at detecting hypericin cell damage.

PMID- 9615787
TI  - mRNA expression of components of the insulin-like growth factor system in breast
      cancer cell lines, tissues, and metastatic breast cancer cells.
AB  - IGF-1 and 2 are thought to be important growth factors for breast cancer.
      However, gene expression of IGFs or IGF receptors in breast cancer tissues, and
      especially in metastatic breast cancer cells, is not well known. Expression of
      mRNA encoding for IGF-1, IGF-2, IGF-receptor 1 and 2, IGF binding proteins- 1 to 
      6, insulin receptor and insulin was determined in the NIH MCF-7 breast cancer
      cell line, in specimens from breast cancer tissues, and in 6 primary breast
      cancer cell cultures obtained from metastatic breast cancer, using rT-PCR
      technique. Specific mRNA sequences encoding for IGF-receptor 1 and 2, IGFBP-2, -4
      and insulin receptor were identified in all cell cultures and most of the tissue
      specimens. Though in most of the tissues additional expression of IGF-1 and IGF-2
      was detected, there was no mRNA encoding for these proteins in MCF-7 cell
      cultures as well as in the primary cell cultures of metastatic breast cancers. In
      none of our specimens mRNA encoding for IGFBP-1, -3, -5, -6 and insulin was
      detectable. IGF-receptor expression in cancer tissues and metastatic breast
      cancer cells supports the hypothesis that IGFs increase tumor cell proliferation
      in vivo. Expression of IGF-1 and IGF-2 in tumor tissues but not in cancer cell
      cultures indicates an IGF expression located predominantly in stromal parts of
      cancer tissues.

PMID- 9615788
TI  - Cell density and oestrogen both stimulate alpha 2-macroglobulin receptor
      expression in breast cancer cell T-47D.
AB  - BACKGROUND: Oestrogen is an important hormone supporting the growth and evolution
      of breast cancer. alpha 2-Macroglobulin receptor/low density lipoprotein receptor
      related protein (alpha 2MR/LRP) is a multifunctional membrane receptor for
      endocytosis of various ligands involved in protease and cytokine activity
      regulation. The effects of oestrogen on the level of expression of this receptor
      may be important in breast tumour progression. MATERIALS AND METHODS: T-47D
      breast cancer cells were grown in media with controlled oestrogen levels, and
      flow cytometry and Western blotting were used to compare their alpha 2MR/LRP
      expression levels. RESULTS: Addition of oestrogen to T-47D cells caused a marked
      increase in alpha 2MR/LRP expression, coinciding with a trippling of cell
      proliferation. T-47D cells at high cell culture densities had similarly raised
      alpha 2MR/LRP expression levels. CONCLUSIONS: Regulation of alpha 2MR/LRP
      expression in the oestrogen receptor-positive breast cancer cell line T-47D can
      be effected by both cell culture density alone and by oestrogen.

PMID- 9615790
TI  - Differential polymerase chain reaction with serial dilutions for quantification
      of MYCN gene amplification in neuroblastoma.
AB  - BACKGROUND: MYCN amplification is a powerful prognostic marker in neuroblastoma.
      Since MYCN status guides therapy results should be available promptly after
      diagnosis. MATERIAL AND METHODS: We used a differential PCR assay to analyze
      neuroblastoma samples obtained from 25 patients diagnosed and treated at our
      Institution. Serial dilutions of test DNA in control DNA were performed prior to
      differential PCR in order to quantitate the MYCN copy number. RESULTS: MYCN
      amplification was identified by differential PCR in five samples out of twenty
      five. The serial dilutions of amplified DNAs performed before the PCR reaction
      allowed a precise estimation of the copy number in the 5 samples with
      amplification. CONCLUSIONS: The present results confirm differential PCR assay as
      an easy, sensitive and rapid technique to evaluate the MYCN gene amplification in
      neuroblastoma. Serial dilutions accurately estimate the gene copy number allowing
      the early onset of the appropriate treatment.

PMID- 9615789
TI  - Life prolonging effect of antitumor agents on postoperative adjuvant therapy in
      the lung spontaneous metastasis model in mice.
AB  - BACKGROUND: We examined the efficacy against pulmonary metastasis of various
      antitumor agents administered after excision of the primary lesion, which was
      induced by injection of RENCA murine renal cancer cells. MATERIAL AND METHODS:
      RENCA cells were implanted into the left kidney of the mice. Nephrectomy of the
      left kidney bearing the resulting primary tumor was performed on day 10 after
      implantation, and administration of antitumor agents was started on day 13 [UFT
      (20 mg/kg), 5'-DFUR (24.6 mg/kg), 5-FU (19 mg/kg), CDDP (7 mg/kg), CPT-11 (50
      mg/kg), TNP-470 (30 mg/kg)]. The efficacies of antitumor agents were evaluated by
      antitumor effect and prolongation of life span. RESULTS: The antitumor effect,
      which was assayed by growth inhibiting ratio of metastatic tumor in the lung, was
      significantly in the UFT (55.5%) and TNP-470 (48.7%) treated groups. 5-FU and
      CDDP exhibited an inhibitory tendency though 5'-DFUR and CPT-11 had no antitumor
      effect. A significant life-prolonging effect was found for UFT and 5-FU, at a T/C
      ratio of 160.8% and 125.7%, respectively. The antiangiogenic activity of the
      agents was examined by counting the number of blood vessels in the metastatic
      nodules in the lungs. TNP-470 exhibited a strong rate of inhibition of 61.5%,
      followed by UFT, CDDP and CPT-11, at about 30% inhibition. The in vitro
      cytotoxicities of 5-FU, SN-38, CDDP and TNP-470 were examined, and 5-FU was
      observed to have potent cytotoxicity. CONCLUSIONS: These results suggest that
      both cytotoxicity to tumor cells and antiangiogenic activity were important
      factors in the life-prolonging effect of antitumor agents in this model, and that
      UFT, which can be administered orally long-term, may be useful in postoperative
      adjuvant therapy.

PMID- 9615791
TI  - In vivo blocking effects of a humanized antibody to human interleukin-6 receptor
      on interleukin-6 function in primates.
AB  - A humanized antibody to human interleukin-6 (IL-6) receptor, MRA, which was
      constructed by grafting the complementary determining regions, is expected to be
      useful as a therapeutic agent for IL-6-related diseases, especially multiple
      myeloma. We examined the ability of MRA to block the in vivo function of IL-6 and
      its serum concentration profile in primates. Cynomolgus monkeys were
      intravenously administered with MRA at doses of 0 (vehicle) or 5 mg/kg, then
      subcutaneously injected with human IL-6 at a dose of 5 micrograms/kg, once a day
      for 7 days. The injections of IL-6 increased blood platelet counts two-fold and
      elevated serum C-reactive protein levels to 0.15 to 0.17 mg/ml. These IL-6
      induced typical responses were completely inhibited by single pretreatment with
      MRA. Serum concentrations of MRA were maintained for a long period; some even at
      one week after administration, were regarded as having sufficient levels to
      inhibit the myeloma cell growth. These findings suggest that MRA may be effective
      in the treatment of IL-6-related diseases.

PMID- 9615792
TI  - Expression and localization of Bcl-2 related proteins in human ovarian cancers.
AB  - BACKGROUND: Interactions between Bcl-2 and its related proteins regulate cell
      death in a number of tissues including the ovary. Some Bcl-2-related proteins
      (Bcl-2, Bcl-xLong, MCl-1, and Dad-1) function as cell death repressors, whereas
      others (Bax, Bcl-xShort, Bak, and Bad) facilitate apoptosis. MATERIALS AND
      METHODS: Immunoblotting and immunohistochemistry using specific antisera were
      performed with a panel of human ovarian carcinomas and normal human ovaries.
      RESULTS: All Bcl-2 related proteins were expressed in normal and malignant
      ovarian tissues. Higher levels of Bcl-2 versus Bcl-xLong were observed in normal
      ovary by immunoblotting, compared to a majority of cancer samples. Increased
      levels of death-inducing Bax were related to malignant transformation across all
      types of ovarian cancer included in this study. CONCLUSIONS: The results provide
      further evidence that a balance of expression among Bcl-2 family members may
      regulate ovarian cancer cell survival.

PMID- 9615793
TI  - Multiple resistance mechanisms in acute nonlymphoblastic leukemia (ANLL).
AB  - The expression of the resistance-related proteins P-glycoprotein 170 (P-170),
      glutathione-S-transferase pi (GST-pi), topoisomerase II (Topo II), thymidylate
      synthase (TS) and metallothionein (MT) was investigated in leukemic cells of 19
      children with newly diagnosed acute nonlymphoblastic leukemia. P-170 was
      expressed in 84%, GST-pi in 37%, TS in 47%, MT in 68%, and Topo II was
      downregulated in 37% of the cases investigated. No resistance factors were found
      in two patients, one positive factor was found in two patients, three factors in
      three patients, four factors in 7 patients, and all resistance factors
      investigated were present in one patient. Patients who developed a relapse
      expressed more than two resistance mechanisms significantly more often than
      patients who remained in remission (p = 0.005). The probability of continuous
      first remission was significantly lower where more than two resistance mechanisms
      were expressed. The results indicate that the higher the number of resistance
      related proteins in childhood ANLL the poorer the prognosis of the patients.

PMID- 9615794
TI  - Intratumoral adoptive immunotherapy with tumor infiltrating lymphocytes (TIL) in
      a melanoma patient leading to regression of local tumor mass. A case report.
AB  - We describe a 52-year old man with a confined massive subcutaneous and
      intramuscular tumor metastasis on his back. He was treated with tumor
      infiltrating lymphocytes (TIL) which were gained from the tumor of his back 3
      months previously. Between 2.5 x 10(7) and 2 x 10(8) TIL were administered, five
      times at 2-week-intervals on day 2 in combination with a continuous subcutaneous
      infusion of interleukin(IL)-2 (1.8 x 10(6) IE/24 hours) over 3 days and a single
      intratumoral injection of a low dose of interferon(IFN)-alpha (1 x 10(6) IE) on
      day 1. There were no severe side effects. Immunotherapy led to a consistent
      regression of the tumor mass. After 3 months, treatment was discontinued due to
      the development of intracranial metastases. In parallel, due to an erythematous
      induration at the infusion site, it became increasingly difficult to infuse IL-2
      subcutaneously. Additionally, high titers of anti-IL-2-antibodies were detected
      in serum. Following cessation of the immunotherapy and brain irradiation, the
      patient's clinical course has remained stable over the past 5 months, suggesting
      that small amounts of TIL with a low-dosed IL-2 may be helpful in the treatment
      of local tumor masses.

PMID- 9615795
TI  - Alkaline phosphatase isoenzymes in detection and follow up of breast cancer
      metastases.
AB  - Alkaline phosphatase isoenzymes in bone and liver metastases of breast cancer
      were determined in 637 patients and during follow up in 116 patients, by agarose
      gel electrophoresis. The activity of total alkaline phosphatase, gamma glutamyl
      transferase, CEA and CA 15-3 was also determined. The sensitivity of bone
      alkaline phosphatase in bone metastases detection was 39%, of electrophoresis
      (total alkaline phosphatase and specific isoenzymes) 48% and of enzymes and tumor
      markers together 85% (n = 62). For liver metastases gamma glutamyl transferase
      had the best sensitivity (100%, n = 19). Even though positive predictive value
      was only 6%, the sensitivity of liver alkaline phosphatase was 58% and of
      electrophoresis 94%. The determination of alkaline phosphatase isoenzymes is a
      non-invasive, in-expensive, reproductable and rapid method to detect progressive
      disease in breast cancer, especially in combination with the tumor markers CA 15
      3 and CEA.

PMID- 9615796
TI  - Elevated vascular endothelial growth factor levels in sera of patients with lung
      cancer.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) overexpression has been
      observed in several malignant tumors, and VEGF level in serum appears to be
      correlated with tumor burden in cancer patients. PATIENTS AND METHODS: Serum VEGF
      levels were measured in 70 patients with lung cancer including 23 with
      adenocarcinoma, 19 with squamous cell carcinoma, 3 with large cell carcinoma, and
      25 with small cell carcinoma, and in 30 patients with benign lung disease and 13
      healthy subjects with an enzyme immunoassay. RESULTS: VEGF levels (mean +/- SD;
      pg/ml) were 834 +/- 699 and 732 +/- 529 in patients with lung cancer and benign
      lung disease, respectively, and were significantly higher than those in healthy
      subjects (264 +/- 129) (P < 0.01). There were no differences between VEGF levels
      categorized by histology, disease stage, or distant metastasis for lung cancer
      patients. CONCLUSIONS: Although serum VEGF levels were increased in lung cancer
      patients, this increase might not have been related to tumor burden.

PMID- 9615797
TI  - GM-CSF in chemotherapy-induced febrile neutropenia--a double-blind randomized
      study.
AB  - Modern chemotherapy programmes render patients susceptible to bacterial and
      fungal infections, and the risk of developing febrile neutropenia after a
      chemotherapy course is in proportion to the severity and duration of the
      neutropenia thus caused. This double-blind randomized study presents details of
      29 patients who developed febrile neutropenia an average of 10 days after their
      course of chemotherapy for different types and stages of malignancy. Fourteen
      received granulocyte/macrophage colony stimulating factor (GM-CSF) and 15 placebo
      during 7 consecutive days as subcutaneous injections. The GM-CSF group
      demonstrated significant increases in total white blood cell count (TWBC) and
      absolute neutrophil count (ANC) from the morning of the third day of the study.
      The study concludes that GM-CSF has an important therapeutic role in the
      treatment of febrile neutropenia that arises during intensive chemotherapy
      programmes but further studies of dosage and therapy duration are required, as is
      the development of methods of assessing bone marrow vitality.

PMID- 9615798
TI  - Tongue cancer treated with brachytherapy: is thickness of tongue cancer a
      prognostic factor for regional control?
AB  - BACKGROUND: We aimed to investigate the predisposing factor for lymph node
      metastasis and examine the influence of thickness for lymph node recurrence in
      oral tongue cancer. METHODS: We analysed 254 patients with early oral tongue
      cancer (T1-2N0) who were treated with brachytherapy from 1967 through 1985.
      RESULTS: T category (p = 0.005), and thickness (p = 0.04) were identified as a
      significant predisposing factors for neck failure. 50%, 40% and 30% were the
      incidences of lymph node metastasis for patients with thickness of tumor more
      than 11 mm, 6-10 mm and 5 mm or less. Furthermore, T category (largest diameter
      of lesion) correlates strongly to thickness of tumor. CONCLUSIONS: Although it is
      not an independent factor, thickness is a significant predisposing factor for
      lymph node metastasis.

PMID- 9615799
TI  - Cisplatin, etoposide, and weekly high-dose 5-fluorouracil and leucovorin infusion
      (PE-HDFL)--a very effective regimen with good patients' compliance for advanced
      gastric cancer.
AB  - We have previously shown that weekly 24-hour infusion of high-dose 5-fluorouracil
      and leucovorin (HDFL), a regimen initially designed for the treatment of advanced
      colorectal cancer, is also effective in the treatment of gastric cancer. This
      HDFL regimen is unique in that it is virtually non-myelosuppressive, and thus
      provides a comerstone on which ideal protocols may be developed. In this
      prospective phase II study, we examined the efficacy and toxicity of PE
      (cisplatin, etoposide)-HDFL, a HDFL-based combination chemotherapy, in the
      treatment of advanced-gastric cancer. This regimen consisted of cisplatin 60
      mg/m2, i.v., D1; etoposide 65 mg/m2, i.v., D1-3; and 5-fluorouracil 2600 mg/m2
      plus leucovorin 300 mg/m2, 24-hour i.v. infusion by an ambulatory infusion pump,
      D2,9,16; repeated every 4 weeks. The major eligibility criteria of the patients
      included: a) a histologically confirmed, objectively measurable, recurrent or
      primary inoperable gastric adenocarcinoma; b) age > or = 75 years; c) a Karnofsky
      performance status > or = 50%; d) an absolute granulocyte count (AGC) > or =
      2000/mm3, and a platelet count > or = 100,000/mm3; e) a serum bilirubin
      concentration < or = 2.0 mg/dl; f) a serum creatinine concentration < or = 1.5
      mg/dl; and g) a signed informed consent. Between March 1992 and June 1996, a
      total of 42 patients were enrolled onto the study. There were 31 men and 11 women
      with a median age of 54 (24-75) years; these included 16 primary metastatic, 3
      locally advanced and inoperable, and 23 postgastrectomy recurrent gastric cancer
      patients. ECOG (Eastern Cooperative Oncology Group) grade III/IV leukopenia and
      thrombocytopenia developed in 34.0% and 11.0% of a total of 229 courses given,
      respectively. There was no treatment-related death. Four patients developed a
      reversible neurotoxicity; and two of them refused further chemotherapy. Among the
      40 patients evaluable for responses, 9 [22.5%; 12-38%, 95% confidence interval
      (C.I.)] patients achieved complete remission, and 20 [50.0%; 33-67%, 95% C.I.]
      patients achieved partial remission. The overall response rate was 72.5% [56-86%,
      95% C.I.]. The overall median survival and median time to progression of the
      responders were 10 and 7 months, respectively. The overall median survival of the
      whole group was 9 months. We concluded that PE-HDFL is a highly effective
      treatment for advanced gastric cancer. The treatment-related toxicity was mild
      and the patients' compliance was satisfactory.

PMID- 9615800
TI  - Frequent p53 mutation in relapsed acute lymphoblastic leukemia with cytogenetic
      instability: a longitudinal analysis.
AB  - P53 mutation, through defects in repairing DNA damages, is associated with
      genomic instability. In 24 adult patients with relapsed acute lymphoblastic
      leukemia (ALL), the status of the p53 gene at different stages was serially
      followed by cytogenetic and polymerase-chain reaction/single strand conformation
      polymorphism (PCR/SSCP) analysis. P53 mutation was detected in 6 patients (25%)
      and all were at relapsed stages: 3 at first relapse, 2 at second relapse and one
      at refractory phase. Loss of the remaining p53 allele was demonstrated in 5 of
      them by cytogenetic and SSCP analysis. Furthermore, all of the p53 mutations were
      associated with appearance of complex cytogenetic changes (CCG), suggesting of
      cytogenetic instability (CGI). The frequency of acquiring p53 mutation during
      leukemic progression is significantly higher in patients with CGI than in
      patients without CGI (6/11 v 0/13, p = 0.003). P53 mutation was detected either
      concurrently (n = 2) or after (n = 4, 2(+)-18 months) appearance of CCG. The
      results suggest that p53 mutation is frequently involved during ALL relapse and
      is closely linked with cytogenetic instability.

PMID- 9615801
TI  - Preliminary report of a controlled trial of MTH-68/B virus vaccine treatment in
      acute B and C hepatitis: a phase II study.
AB  - Eighty four patients with viral hepatitis attributed to infection with hepatitis
      B virus (HBV) (n = 43) or hepatitis C virus (HCV) (n = 41) were included in this
      study employing the MTH-68/B vaccine, an attenuated variant of Bursal Disease
      Virus. Twenty of the 43 patients in the HBV group, and 22 of the 41 HCV patients
      were treated with MTH-68/B. The remaining patients received conventional therapy.
      Significantly more patients progressed into active chronic hepatitis on
      conventional therapy (13% of HBV and 26% of HCV cases respectively) than in the
      vaccine treated groups (0% and 9%). Relapses occurred less frequently in the
      vaccine treated groups (5% of HBV and 32% of HCV) than in the control groups (9%
      and 79%), while remissions within one month of treatment were observed more often
      in the vaccine treated groups (both 50% respectively) than in the control groups
      (26% of HBV and 21% of HCV patients respectively). The duration of hepatitis was
      also considerably shortened by MTH-68/B treatment in both HBV (from 7.5 +/- 3.7
      to 5.9 +/- 3.0 weeks) and HCV patient groups (from 8.9 +/- 7.4 to 5.3 +/- 4.4
      weeks). The data presented suggest that attenuated, non-pathogenic viruses may be
      of significant benefit for patients with viral hepatitis B and C infections.

PMID- 9615802
TI  - Detection of circulating cancer cells by nested reverse transcription-polymerase
      chain reaction of cytokeratin-19 (K19)--possible clinical significance in
      advanced gastric cancer.
AB  - Intermediate filament cytokeratin-19 (K19) protein is expressed in normal and
      malignant gastrointestinal epithelial cells, but not in peripheral blood (PB).
      Small amount of circulating gastric cancer cells can be detected by a sensitive
      nested reverse transcription-polymerase chain reaction (RTPCR) with primers
      specific for K19 mRNA. Thirty-four PB samples obtained from patients with
      inoperable/metastatic gastric cancer were examined. The mononuclear cell (MNC)
      fraction was collected by Ficoll centrifugation, and followed by total RNA
      extraction by acid guanidinium thiocyanate-phenol-chloroform method. RNA from 8
      gastric cancer cell lines and the mononuclear cells of 33 healthy adults were
      used as positive and negative controls, respectively. DNA fragment of 774 bp
      amplified by the internal primers was found to be a highly reliable marker for
      K19 mRNA expression. The sensitivity of detection was between 1 and 10
      cells/10(6) normal MNCs. The K19 transcripts were detected in 20.6% (7/34; 8-37%,
      95% C.I.) of PB samples. None of the other pertinent clinicopathological
      features, including the disease extent and the histopathologic types of the
      tumors, were related to the expression of K19 in PB. All 34 patients had been
      treated by systemic chemotherapy. Among the 17 non-responders to chemotherapy,
      the survival of the 4 patients with detectable K19 was significantly shorter than
      that of 13 patients without detectable K19 in their circulating blood (p =
      0.014). However, the survival impact of K19 was less significant in the other 17
      patients whose tumors had responded to systemic chemotherapy. Of the whole group
      of patients, the median survival of the 7 and 27 patients with and without
      detectable K19 in their circulating blood was 1 and 3.5 months, respectively (p =
      0.368). We concluded that detecting circulating cancer cells by K19 nested RT-PCR
      is associated with poor prognosis of gastric cancer, particularly in those
      patients who are not responsive to systemic chemotherapy.

PMID- 9615803
TI  - p53 and cyclinX D1 protein expression in carcinomas of the parotid gland.
AB  - BACKGROUND: p53 and cyclin D1 genes play a central role in the regulation of the
      G1 phase of the cell-cycle, and are frequently involved in head and neck
      tumorigenesis. MATERIALS AND METHODS: By means of immunohistochemistry, we
      retrospectively investigated the overexpression of cyclin D1 and p53 genes in a
      series of 28 parotid gland carcinomas. The immunohistochemical analysis was
      performed using the ABC method and the antibodies DCS6 (for cyclin D1) and CM1
      (for p53). RESULTS: p53 was overexpressed in 12 (42.9%) and cyclin D1 in 6 cases
      (21.4%). No significant association was found between p53 or cyclin D1 expression
      and the evaluated clinicopathological parameters of tumor extension, clinical
      stage, and lymph node or distant metastases. Nevertheless, it is worth noting
      that all of the patients with a high expression of p53 died of their disease.
      CONCLUSIONS: The present data confirm the role of p53 abnormalities in the
      pathogenesis of salivary gland carcinoma and report, for the first time, the
      involvement of cyclin D1 gene in these tumors.

PMID- 9615804
TI  - Cardiac malignant lymphoma: a case report.
AB  - A 76 year old man, who had undergone tonsillectomy for non Hodgkin's malignant
      lymphoma, died suddenly in rapidly evolving cardiogenic shock with
      electrocardiographic signs of acute lateral myocardial infarction. Post mortem
      examination showed three cardiac lesions, two in the left ventricle and one in
      the right atrium, corresponding to the "crista terminalis". Histologic
      examination of autopsy samples confirmed the presence of lymphoma in the heart,
      partially affecting the sino atrial node (NSA) but excluding other sites. There
      was no evidence of acute myocardial infarction in spite of the clinical signs and
      symptoms. An infarction-type electrocardiographic pattern associated with
      conduction disturbances in patients with lymphoma should suggest the possibility
      of cardiac localization of the disease.

PMID- 9615805
TI  - Analysis of long-term survivors after platinum containing chemotherapy in
      advanced non-small cell lung cancer.
AB  - Among 195 patients with locally advanced or metastatic non-small cell lung
      cancer(NSCLC), we evaluated the characteristics of two-year survivors. All the
      patients with stage IIIA-IV disease received platinum containing combination
      chemotherapy at Tsukuba University Hospital between 1985 and 1996. Fourteen
      patients (7.2%) and 7 patients (3.6%) survived for more than 2 and 3 years,
      respectively. Ten of the 14 responded to initial chemotherapy, and 9 patients
      received additional treatment such as thoracic irradiation and/or surgical
      resection. Three of the 14 patients survived more than 5 years disease free, one
      of them survived more than 10 years. From the results uni- and multivariate
      analyses of these patients, early stage of the disease, low number of metastatic
      site, without associated lung disease were confirmed as significant determinants
      of survival. This study revealed that a small proportion of patients with
      advanced NSCLC might be potentially curable with appropriate treatment.

PMID- 9615806
TI  - Non-Hodgkin's lymphoma (NHL) of the oral cavity.
AB  - BACKGROUND: The treatment of NHL in the head and neck region is complex because
      of the numerous variables that are involved. Reports in the recent literature on
      NHL of the oral region have dealt with one or two individual cases and routine
      treatment guidelines do not exist. Local lesions are responsive to radiotherapy
      as well as to chemotherapy, but the cure rates are discouragingly low. PATIENTS
      AND METHODS: We report a case of a painful swelling of the lower left gingiva.
      Local biopsy and a systemic work-up (labs, x-rays, eco scan, CT, bone marrow
      aspiration and biopsy) was performed. RESULTS: The biopsy of the oral lesion
      disclosed a malignant NHL; other examinations failed to find other foci of the
      lymphomatous process. CONCLUSIONS: This case of primitive NHL of the oral cavity
      summarises the main characteristics of this rather uncommon pathology: a)
      difficult diagnosis at presentation, often misdiagnosed for other more common
      oral diseases b) the importance of a local biopsy; c) rapid evolution; d) a good
      response to chemotherapy; e) poor prognosis.

PMID- 9615807
TI  - Treatment of recurrent high grade astrocytoma; results of a systematic review of
      1,415 patients.
AB  - OBJECTIVE: The optimum treatment strategy for recurrent high grade glioma
      (anaplastic astrocytoma and glioblastoma multiforme) remains undefined. The
      objective of this report is to present a systematic analysis of the published
      clinical trial literature on the therapy of this disease. METHODS: A study
      protocol was prospectively developed outlining the objectives and methods of the
      analysis such as; literature search strategy, eligibility criteria for published
      trials to be included, key data elements to be extracted, and a plan for
      statistical analysis. Variables of interest were, those describing key features
      of the study such as publication date and geographic location of reporting
      institution, characteristics of study population including functional status,
      details of patient treatment, treatment sequencing and data on clinical outcomes
      of interest, i.e. time to tumor progression and overall survival. Data were
      analyzed using SAS version 6.11. Summary statistics were calculated for the
      primary outcome variables. Data on recognized prognostic variables were recorded
      in order to adjust the analysis for these parameters. RESULTS: A total of 40
      trials (36 non-randomized controlled trials; nRCTs and 4 randomized controlled
      trials: RCTs) were included in the analysis. Thirty-two of the eligible trials
      were chemotherapy trials while 7 were radiation therapy trials. One surgical
      trial met eligibility criteria. A total of 47 treatment arms were analysed which
      included 1,415 patients. Five chemotherapy groups were studied, i.e. interferons,
      nitrosoureas, platinums, platinums + nitrosoureas and others. The nitrosoureas
      were found to significantly extend time to tumor progression compared to all
      other drugs (26.9 weeks). The nitrosoureas and platinums appear to be the most
      active agents with regard to overall survival (over 32.0 weeks) as compared with
      the other drug categories. Patients treated with both a nitrosourea and a
      platinum compound showed the longest overall survival (40.0 weeks) although this
      was not significantly different from these drugs used as single agents. Average
      median survival for patients treated with radiation therapy was 44.7 weeks
      although selection bias makes these data difficult to compare with those derived
      from studies of chemotherapy. No definite conclusions can be made regarding
      surgical therapy in this setting due to limited data. CONCLUSIONS: The
      nitrosoureas and platinums, either as single agents or as combination
      chemotherapy, appear to be the most active agents in this disease although few,
      well designed chemotherapy trials are available for analysis. Due to the
      limitations of the available data on radiation therapy and surgery, as outlined
      in this report, additional, well designed clinical trials are needed to define
      the appropriate role for these modalities in the treatment of recurrent high
      grade glioma.

PMID- 9615808
TI  - Hydration regimen and hematological toxicity of a cisplatin-based chemotherapy
      regimen. Clinical observations and pharmacokinetic analysis.
AB  - The administration of 100 mg/m2 Cisplatin (CDDP) in five 20 mg/m2 daily infusions
      together with bolus 5-Fluorouracil (5FU) allows patients with advanced head and
      neck cancer (HNC) to be treated with a rapidly alternating chemoradiotherapy
      regimen in an out-patient setting. Due to the extremely low rate of acute renal
      failure, the induction of forced diuresis is not mandatory, although hydration is
      usually performed at every CDDP administration. In this retrospective analysis of
      73 homogenously treated HNC patients, the influence of hydration on hematological
      toxicity was studied. A lower incidence of grade II to IV acute myelosuppression
      (57% vs 92%; p < 0.005), together with a lower rate of anemia lasting two weeks
      or more (13% vs 46%; p < 0.009), were seen in the group of patients treated with
      CDDP along with a forced hydration scheme (2000 ml normal saline and 20 mg
      furosemide before the CDDP infusion) when compared to patients on a non-forced
      diuresis regimen (no furosemide and 1500 ml normal saline). The lower
      hematological toxicity translated into a better compliance to treatment. No
      differences in terms of other toxicities or response rate were evident between
      the two groups. A pharmacokinetic study with a cross over design was performed on
      7 patients, and suggests that the first day Pt kinetics are not affected by the
      hydration scheme used, although a significantly lower Pt urinary concentration
      was found in the forced diuresis group. A further kinetic analysis performed on
      one additional patient over the entire five-day period of two consecutive cycles
      showed a marked increase in the AUC of filterable Pt and in the unbound Pt
      fraction (fu) from the second to the fifth day in the forced hydration course,
      while this was not the case in the non-forced hydration course. Results from this
      kinetic study support the hypothesis of a lowering of Pt reactive species after
      repeated CDDP-furosemide treatments and an influence of furosemide-induced
      diuresis on Pt binding to plasma proteins.

PMID- 9615809
TI  - The efficacy of hyperthermia combined with radiation therapy for high-grade soft
      tissue sarcoma.
AB  - BACKGROUND: We have investigated the efficacy of preoperative hyperthermia
      combined with radiation therapy (HIRP) in cases of soft tissue sarcoma (STS) that
      could be consequently treated with limb salvage. MATERIALS AND METHODS: Thirteen
      patients with STS in an extremity received HIRP at our institution. Local
      hyperthermia for 1 hour was administered eight to ten times. Radiation therapy
      (40-60 Gy) was administered at 2 Gy per session. The operation was performed at 2
      or 3 weeks after HIRP. RESULTS: Limb salvage surgery was achieved in 12 patients.
      No local recurrence was observed during a mean follow-up of 27 months. 7 patients
      had shown only a partial response to the HIRP. There was no correlation between
      the histological response and the observed reduction in tumor volume.
      CONCLUSIONS: The results of this study suggested that HIRP was an effective local
      treatment for limb salvage in limb-threatening STS.

PMID- 9615810
TI  - Elevated reversible and irreversible lipid peroxidation in human oesophageal
      cancer.
AB  - BACKGROUND: Cancer of the oesophagus is the most common gastrointestinal
      malignancy in South African blacks. The aim of this study was to determine the
      reversible and irreversible lipid peroxidation in cancer of the oesophagus; a
      feature that has not been assessed before in this or other cancer tissue.
      METHODS: Biopsies and plasma from 39 patients with cancer of the oesophagus and
      22 biopsies and plasma from non-cancer patients were analysed for the
      irreversible lipid peroxide product malondialdehyde (MDA) and other reversible
      lipid peroxide products (LPO) by the thiobarbituric acid-reactive substances
      (TBARS) method. RESULTS: The mean (+/- SEM) for MDA in plasma from normal
      patients was 1.697 (0.149), and for cancer patients 4.23 (0.417) nmol MDA/ml. The
      tissue MDA for normal patients was 0.807 (0.154), and for cancer patients 2.530
      (0.379) nmol MDA/mg protein. The mean (+/- SEM) for LPO in plasma from normal
      patients was 1.929 (0.281), and for cancer patients 12.607 (1.451) nmol MDA/ml.
      The tissue LPO for normal patients was 2.957 (0.306), and for cancer patients
      16.320 (1.868) nmol MDA/mg protein. All the MDA and LPO values for cancer
      patients were significantly elevated (p < 10(-4)). In oesophageal cancer 85% of
      the lipid which was peroxidized, was of the reversible type. CONCLUSIONS: This
      elevated reversible LPO levels in plasma and oesophageal tissue of cancer
      patients support the notion that the oxy-radicals in cancer are not under proper
      metabolic control. Therefore, human oesophageal cancer does not progress to self
      regression or destruction but rather to more mutagenic changes probably due to
      high reversible lipid peroxidations.

PMID- 9615811
TI  - Melatonin as biological response modifier in cancer patients.
AB  - The neuroendocrine system modulates the immune response through neuropeptides and
      neurohormones, findings which point to the existence of a neuro-endocrine-immune
      system regulatory axis. At the same time, there is growing evidence that the
      pineal gland has anti-neoplastic properties, which include the action of its
      principal hormone, melatonin (MLT), on the immune system through the release of
      cytokines by activated T-cells and monocytes. The present study was carried out
      on 31 patients (19 males and 12 females, age range 46-73 years) with advanced
      solid tumors (7 gastric, 9 enteric, 8 renal, 5 bladder, 2 prostate) who either
      failed to respond to chemotherapy and radiotherapy or showed insignificant
      responses and were therefore shifted to MLT therapy (10 mg/die orally for 3
      months). We obtained blood samples just before the start of MLT administration
      and after 30 days of therapy. Plasma was collected in EDTA tubes on ice,
      immediately centrifuged at 4 degrees C and stored frozen at -80 degrees C;
      samples were measured by immunoradiometric assays (Medgenix-Fleurus, Belgium) for
      tumor necrosis factor alpha (TNF), interleukin-1, 2 and 6 (IL-1, IL-2, IL-6) and
      interferon gamma (IFN). We used Student's paired t-test to compare each patient's
      cytokine circulating levels before and after MLT administration and found a
      significant differences (p < 0.05). After 3 months of therapy, none of our
      patients displayed adverse reactions to MLT or had to discontinue treatment.
      Nineteen patients (61%) showed disease progression. The other 12 (39%), however,
      achieved disease stabilization with no further growth of either the primary tumor
      or of secondaries; moreover, they experienced an improvement in their general
      well-being, in terms of Tchekmedyian's criteria, associated with a significative
      decrease of IL-6 circulating levels. These findings are consistent with the
      hypothesis that MLT modulates immune function in cancer patients by activating
      the cytokine system which exerts growth-inhibitory properties over a wide range
      of tumor cell types. Furthermore, by stimulating the cytotoxic activity of
      macrophages and monocytes, MLT plays a critical role in host defence against the
      progression of neoplasia.

PMID- 9615812
TI  - Human glioma associated intermediate filament proteins: over-expression, co
      localization and cross-reactivity.
AB  - The identification of human brain tumor-associated markers could facilitate the
      development of new diagnostic and therapeutic strategies for these malignancies.
      The type III intermediate filament proteins (IFPs): vimentin, desmin and glial
      fibrillary acidic protein (GFAP) were studied in human glioma tissue extracts, in
      sera from glioma patients and in low passage glioma cell lines prepared from
      primary cultures of freshly dissected tumors. Radioimmunoassay (RIA) studies,
      using anti-GFAP, anti-desmin and anti-vimentin mAbs, showed high levels of these
      proteins in glioma extracts. Binding studies with authentic IFPs indicated the
      absence of circulating antibodies against these proteins in the sera of glioma
      patients. On the other hand, these sera showed high levels of vimentin. Binding
      studies with these antibodies using RIAs and western immunoblotting, showed that
      while anti-GFAF mAbs were specific to GFAP, anti-desmin mAb cross-reacted
      completely with GFAP, anti-vimentin mAb cross-reacted substantially with desmin
      and GFAP. Immunofluorescence staining of frozen sections revealed high levels of
      neurofilaments in gliomas and strikingly low levels in normal brain tissue.
      Double immunofluorescence staining showed co-occurrence of all three IFPs in the
      same filaments. This suggests either co-expression or cross-reactivity of these
      proteins due to their high degree of homology. Thus, caution should be exercised
      in the use and interpretation of immunohistochemical data using antibodies to
      IFs.

PMID- 9615813
TI  - Lack of correlation between tumor markers (CA 125 and SCC) and systemic lupus
      erythematosus activity.
AB  - BACKGROUND: Recently, tumor markers (CA 125 and SCC) have been suggested as
      possible activity markers of systemic lupus erythematosus (SLE), but study
      results have been contradictory. OBJECTIVE: The aim of this study was to evaluate
      the possible relationship between CA 125 and SCC serum levels and SLE activity.
      PATIENTS AND METHODS: Serum levels of CA 125 from 59 patients and levels of SCC
      from 53 patients with SLE were analyzed. Both tumor markers were determined by
      ELISA, considering 35 U/ml (CA 125) and 2.5 ng/ml (SCC) respectively as the upper
      limit of normality. The serum levels of these tumor markers were correlated with
      the SLE disease activity index (SLEDAI). RESULTS: The CA 125 concentrations in
      active SLE (mean 13.8 + 15.3) were similar to those in inactive patients (mean
      13.1 + 11.7 U/ml). Significantly high CA 125 serum levels were found only in SLE
      patients with nephrotic syndrome (p = 0.001). No significant differences were
      found in SCC serum levels in SLE patients with (mean 0.9 +/- 0.8 ng/ml) or
      without activity (mean 1.1 +/- 1.3 ng/ml). Likewise, no relationship between SCC
      serum levels and parameters related to SLE activity were found, excluding slight
      increases associated with renal failure. CONCLUSIONS: The correlation that some
      authors have found between elevated serum levels of CA 125 and SLE activity is
      only associated with the presence of nephrotic syndrome. Likewise, SCC is not
      related with SLE activity and the increases found may be due to renal failure.

PMID- 9615814
TI  - [Effectiveness of adjuvant therapy for patients with early-stage (I-IIa) breast
      cancer].

PMID- 9615815
TI  - [Megestrol acetate as hormone therapy in oncology].
AB  - The structure, properties and therapeutic effect of a synthesized progestin-
      megestrol acetate (Megace) are discussed. It is most useful in the management of
      local and metastatic tumors of the breast and endometrium as well as anorexia
      cachexia syndrome. It is suggested that other applications in hormone therapy and
      new ways of avoiding untoward side-effects (weight gain) may be found.

PMID- 9615816
TI  - [Surgical treatment of superficial melanoma of the skin].
AB  - The 12-year end-results of standard "wide" and sparing "narrow" excision of
      superficial skin melanoma are compared. The results were contributed by a joint
      study of the WHO Collaborating Centers for Evaluation of Methods of Diagnosis and
      Treatment of Melanoma headed by Dr. U. Veronesi and Dr. N. Cascinelli and 23
      other centers in different countries (the Blokhin and Petrov Centers in Russia).
      The investigation comprised 612 patients. After randomization, "narrow" excision
      of primary tumor with 1 cm-wide margins was performed in 305 patients. In the
      remaining 307 patients, "wide" excision left margins within 3 cm. Tumor was
      identified as superficial on the basis of thickness (Breslow), the threshold
      being 2 mm-thick invasion. This same prognostic indicator was used in both
      groups. Another one was 12 year-long recurrence-free survival. The sparing
      excision of primary cutaneous melanoma with a thickness under 2 cm proved
      effective.

PMID- 9615817
TI  - [Current principles and methods of radical therapy for locally extensive
      esophageal and gastroesophageal cancer].
AB  - The results of radical surgical and combined treatment of 124 cases of esophageal
      and cardioesphageal tumors are presented. Extensive local disease (stage III, T2
      4N0-2M0) was diagnosed in 113 patients (91.1%). Esophagoectomy with
      transmediastinal esophagogastroplasty and cervical esophagostomy proved most
      useful for esophageal tumor, while extensive surgery after Lewis in combination
      with extirpation or proximal resection of the stomach--for proximal gastric
      disease involving the esophagus. Combined surgery with resection of adjacent
      organs was carried out in 50%. Post-operative mortality rates were reduced to
      7.1% due to application of effective surgical, anesthetic and intensive care
      procedures. The 3-year survival rate was 26.5%. Prognosis improved significantly
      when radiation was used prior to dissection of lymph nodes.

PMID- 9615818
TI  - [Significance of adjuvant radiotherapy in the surgical treatment of patients with
      non-small-cell lung cancer].
AB  - The study comprised 702 patients radically operated on for non-small cell cancer
      of the lung: surgery alone--351; radiation + surgery --110; (Eighty-seven
      patients of the latter group received an intensive course of radiation with a
      total target dose (TTD) of 20 Gy); surgery + fractionated radiation with TTD 50
      55 Gy--195; radiation + surgery + radiation--46. No significant increase in
      overall or stage-related survival was registered for application of either
      modality as compared with controls. To establish indications for adjuvant
      radiotherapy, a prognostic factor study was undertaken using the regression model
      of Cox. The presence of metastasis in mediastinal nodes (N2) is considered the
      main indication for combined treatment. In the absence of metastasis in the
      regional nodes (N0) or in case of metastatic involvement of the nodes of the
      radix pulmonis (N1), adjuvant radiotherapy was not followed by a significant
      increase in survival rates even in cases of extensive local primary tumor (T3)
      and other unfavorable factors. Surgery + radiation or radiation + surgery +
      radiation for extensive non-small cell disease (T1-3N2M0) led to a significant (p
      < 0.05) rise in overall and recurrence-free survival rates and reduced the risk
      of local recurrences as compared with surgery alone.

PMID- 9615819
TI  - [Parameters of cellular immunity in lung cancer patients with different types of
      adaptation reactions during polychemotherapy].
AB  - A relationship between cellular immunity and general adaptation syndrome in the
      course of CAM polychemotherapy has been investigated. The results point to a lack
      of lymphopenia, lower levels of T-suppressors and higher instability of
      immunological indices in patients showing increased activation reaction and
      maximum antitumor resistance during cytostatic therapy, unlike in those in
      stress. This opens an opportunity for correction.

PMID- 9615820
TI  - [Morphologic factors influencing the prognosis of squamous-cell cervical cancer].
AB  - The role of such morphological factors as depth of invasion, tumor growth
      pattern, distinct boundary of tumor, presence of tumor emboli in vessels, level
      of lymphocyte-plasmocyte infiltration and mitotic activity of tumor cells in the
      course and prognosis of squamous-cell cervical carcinoma has been studied.
      Invasion depth, tumor pattern, tumor boundary and emboli in the vessels are
      prognostically relevant in lymph-related dissemination and recurrence of the
      disease.

PMID- 9615821
TI  - [Primary multiple neoplasm of the endometrium and adjuvant hormone therapy in
      patients with breast cancer].
AB  - The contribution made by adjuvant hormone therapy in the development of primary
      multiple endometrial adenocarcinoma (EA) in patients with breast tumors (BT) is
      not quite clear. The study was based on the data on 5,790 cases of BT treated at
      our Clinic and 4,447 females screened for hormone-dependent neoplasms. Patients
      with BT were found to be at high cumulative risk for endometrial carcinogenesis
      caused by general factors of risk and pathogenesis. The risk was particularly
      high in BT (stage 1) within 12 months after treatment. There was no correlation
      between tamoxifen treatment and significant increase in EA frequency. Promotion
      of tumor proliferation by tamoxifen was identified in endometrial tissue in 62
      patients with BT. This may facilitate clinical manifestations of another latent
      EA in such patients. Dynamic surveillance of the endometrium and ovary should
      include ultrasonography of pelvic organs and cytologic examination (smears) of
      the ecto- and endocervix and endometrial aspiration biopsy.

PMID- 9615822
TI  - [Clinical and morphologic diagnosis of uterine sarcoma].
AB  - The results of a clinico-morphological evaluation of the data on 419 patients
      suffering from uterine sarcoma are presented. It is recommended that dynamic and
      ultrasonic surveillance of patients with uterine myoma, particularly those in pre
      or postmenopause, be carried out for timely detection of leiomyosarcoma.
      Premorbid pathogenetic status in patients with mixed mesodermal neoplasms and,
      especially, carcinosarcomas has much in common with the relevant characteristics
      of hormone dependent adenocarcinoma of the endometrium. Cytologic examination of
      the uterus and endocervix in patients with endocrine metabolic disorders and
      myoma may detect mixed mesodermal tumors and uterine stromal sarcoma at earlier
      stages. Mitotic index, meta-prophase factor and number of cell mitosis
      determination is instrumental in differential diagnosis of proliferating myoma
      and leiomyosarcoma. Among the unfavorable prognostic factors in leiosarcoma are:
      high anaplasia and mitotic activity (in excess of 10/1000) and marked
      infiltrative growth, while, in mixed mesodermal tumor (carcinosarcoma included),
      it is deep invasion (more than 1.0 cm).

PMID- 9615823
TI  - [Betaleukin (human recombinant interleukin-1beta) for the prevention and
      correction of toxic leukopenia in chemotherapy of malignant neoplasms].
AB  - The marked and quick response to betaleukin, a preparation of recombinant human
      interleukin-1 beta, was demonstrated in 77 cases of extensive solid neoplasms and
      non-Hodgkin's disease, suffering combination chemotherapy-induced toxic
      leukopenia. Leukopoiesis was effectively stimulated by intravenous
      administration, of 10-20 ng/kg weight, dropwise for 5 days. Due to adjuvant
      betaleukin in identical dosage, chemotherapy was continued, in moderate
      leukopenia, without causing leukocyte count to drop. The untoward side-effects
      (chiefly. hyperthermia including fever) were reversible and did not hamper
      treatment.

PMID- 9615824
TI  - [Assessment of degree of malignancy in non-Hodgkin B-cell lymphoma with
      immunophenotyping].
AB  - Due to immunophenotypic examination of bioptic samples from 30 patients with non
      Hodgkin's lymphoma (NHL), malignancy of B-cell NHL was identified at an early
      stage of diagnosis, before histological analysis yielded the results. Negative
      expression of T-cell antigens, monoclonal character of light-weight chains of
      immunoglobulins, positive expression of B-cell antigens and marked expression of
      CD5+ are immunologic markers of low-malignancy B-cell NHL. A similar
      immunophenotypic pattern, involving negative expression of CD5- and positive one
      for Calla-antigen as well as one identifiable by monoclonal non-cluster antibody
      IPO3, is a marker of highly-malignant B-cell NHL.

PMID- 9615825
TI  - [Clinical introduction and results of simultaneous resection and repair in
      esophageal cancer].
AB  - The data on 80 cases of radical resection and extirpation of the esophagus for
      intrathoracic tumors entailing esophagogastroplasty are discussed. Esophageal
      extirpation with resection of the proximal part of the stomach, sufficient
      lymphadenectomy, simultaneous transmedianal esophagogastroplasty and formation of
      cervical esophago-gastrostomy proved the most radical. The 3-year complication
      and mortality rates were 20.0 and 5.0%, respectively. The procedure yields the
      best functional results, too. It is understood that the long and tortuous process
      of development of a new surgical procedure inevitably involves frequent
      postoperative complications, which, however, can be effectively treated if
      measures are taken to improve surgical technique and intensive care standards.
      The end-results still leave much to be desired--the 3-year survival rate was
      24.0, 5 years--8.0%.

PMID- 9615826
TI  - [Surgical treatment of soft tissue sarcomas of the pelvic girdle].
AB  - Wide excision of neoplasm is most frequently used in surgery for soft tissue
      tumors, on appropriate sites and whenever the "envelope" can be preserved. The
      most frequent site of pelvic girdle soft-tissue tumors was the glutal area (39.0
      +/- 4.8%). Out of 100 patients with such sarcomas, wide excision of tumor was
      performed in 82, and tumor excision + bone resection--18. The former procedure
      was mostly used in the management of liposarcomas (26.5 +/- 4.2%), while the
      latter--in synovial sarcoma (33.3 +/- 4.9%).

PMID- 9615827
TI  - [Ultrasound differentiation of fibroadenoma and diagnosis of minimal carcinoma of
      the breast].
AB  - The investigation was based on the ultrasound and mammographic examination of 630
      patients with different patterns of fibroadenoma and 23--with carcinoma of the
      breast. Sonography should be carried out in step with menstrual cycle when
      diffuse hyperplasia of glandular tissue is registered. Minimal lobular cancers
      present most difficulties. Detection of a "node" should not be seen as the
      dividing line between tumor and fibroadenoma. In cases of fibroadenoma,
      sonography should be sometimes supplemented by mammography. Fine-needle
      aspiration biopsy should be used to clarify radiological evidence.

PMID- 9615828
TI  - [Comparison of transabdominal and transvaginal sonography in the diagnosis of
      female genital malignancies].

PMID- 9615829
TI  - ["Second-look" surgery and diagnostic laparoscopy in the combined and
      comprehensive therapy of patients with ovarian cancer].
AB  - The data on 503 cases of ovarian malignancies were evaluated to work out
      indications for and clinical assessment of revision laparotomies. Second-look
      surgery was carried out in the following situations: (1) tumor elements found in
      the washings of the peritoneum in Douglas' space and high blood-serum levels of
      CA-125 (8 patients with stage I-II tumors, in clinical remission); (2) during
      remission, after 6-10 courses of polychemotherapy (13 patients with stage III-IV
      tumors); (3) during remission, after non-radical primary surgery (117); (4)
      suspected recurrence (144); (5) recurrence-free surgical pathology, e.g. ventral
      hernia, requiring laparotomy (22). Patients without repeated laparotomy (199)
      were in control. During remission, surveillance can be carried out using
      cytologic, ultrasound and immunoradiologic techniques since laparoscopy fails.
      The latter is useful, for diagnostic purposes, in case of discrepancy between
      clinical and ultrasound evidence as well as during monitoring in patients in
      clinical remission who show unfavorable levels of CA-125 and poor results of
      sonographic. Laparotomy is indicated prior to chemotherapy of inoperable tumors
      for morphologic verification of diagnosis. Indications for second-look operations
      can be significantly decreased considering the latest improvements in non
      invasive monitoring technique. Laparoscopic examination can effectively serve the
      same purposes.

PMID- 9615830
TI  - [Radiologic and ultrasonographic assessment in staging and in the evaluation of
      therapeutic effectiveness of non-Hodgkin lymphomas].
AB  - The data on the radiological and ultrasound examination of 912 patients with non
      Hodgkin's lymphoma (NHL) are presented. Involvement of thoracic and abdominal
      lymph nodes and organs was recorded in two-third of NHL cases, with aggressive
      pattern, particularly, those involving the intestines, skeleton, pleura and
      pericardium prevailing (80%). In the nodular disease of the lung, pleura, breast
      and exophytic tumors of the gastrointestinal tract, the end results were much
      better. Prognosis was less favorable with perinodal infiltration and lymphangitis
      in the lungs, wet pleurisy and pericarditis, infiltrative disease of the
      gastrointestinal tract, breast and involvement of the small intestine. Sonography
      proved most effective in the evaluation of lymph nodes status (sensitivity--85.8;
      specificity--99.4%). However, only 10% of focal lesions in parenchymal organs
      were reliably detected.

PMID- 9615831
TI  - [Multicenter clinical trial of the antitumor drug Dioxadet (phase II)].
AB  - A stage II of the joint clinical study of Dioxadet, an ethylene imine drug, was
      carried out to evaluate its therapeutic effect in 229 patients and side-effects
      in 239 patients with malignancies of various sites. Marked therapeutic effect was
      observed in ascitic malignancies of the ovary and a moderate one--in disseminated
      breast cancer. The most frequent side-effect was reversible myelodepression,
      often delayed.

PMID- 9615832
TI  - [Therapeutic effect of amigluracil aerosol inhalation on radiation- and bleomycin
      induced pulmonitis in patients with malignant lymphomas].
AB  - The report deals with the first experience of successful administration of
      soluble amigluracil, a synthesized pyrimidine derivative of methyluracil, which
      was inhaled with aerosols to treat acute, chronic radiation-related and bleomycin
      induced pulmonitis. No side-effects, including allergy, were observed.

PMID- 9615833
TI  - [Therapeutic potential of Granisetron (Kitryl) for the prevention of nausea and
      vomiting induced by cytostatic drugs].
AB  - Oral administration of 2 mg kitryl effectively controlled nausea (82.5-96.7%) and
      vomiting (97.3-99.1%) induced in 127 patients with malignant lymphomas and solid
      tumors, who received highly emetic cytostatic MOPP, ABVD, CHOP, CHOEP, EVAP, VP
      and CMP therapy. The antiemetic effect of oral administration was identical to
      that of intravenous injection of 3 mg.

PMID- 9615834
TI  - [The use of transcranial electrostimulation for pain relief in cancer patients].
AB  - The report discusses whether transcranial electrostimulation in cancer patients
      can be accepted. A number of tumors were inhibited in an experiment using 120
      rats. The procedure used in 80 cancer patients was followed by favorable changes
      in the concentration of several hormones. The antinociceptive action of
      electrostimulation is similar to that of narcotic analgetics.

PMID- 9615835
TI  - [Methodologic and organizational problems of establishing a State Cancer
      Registry].

PMID- 9615836
TI  - [Estimated expenditure for treatment of cancer patients at the Clinic at the
      Prof. N.N. Petrov Oncology Research Institute].

PMID- 9615837
TI  - [Breast cancer as a social problem and common aspects with other oncologic
      patients].
AB  - Problems of peculiar relationships between oncologists, society and general
      public, on the one hand, and cancer patients, on the other, are discussed with
      respect to breast cancer. It is suggested that if one's right to take care of
      one's life is to be honored, cancer patients are to have access to more
      information on their disease must doctor should be prepared to give away more of
      it in their conversations. Once one is aware of responsibility for one's health,
      the advantages of an earlier visit to a doctor and, conversely, the tragedy of a
      belated call become quite apparent. Such awareness is not feasible unless society
      becomes the patients ally in every-day activities of cancer control. This
      approach calls for a revision of somewhat out-dated deontological principles as
      well as measures aimed at getting the public to change their attitudes towards
      cancer patients. Simultaneously, the medical profession must receive an education
      in dealing healthy people and cancer patients. The engagement of former cancer
      patients, who have an experience of a program of social rehabilitation, will make
      the efforts to cure those who are still sick more meaningful and boost their
      morale.

PMID- 9615838
TI  - [Priorities and perspectives in the treatment of gastric cancer].

PMID- 9615839
TI  - The many faces of asthma. Introduction. Proceedings from a symposium held at the
      annual meeting of the European Academy of Allergology and Clinical Immunology in
      Rhodes Greece, June 1997.

PMID- 9615840
TI  - The complementary role of glucocorticosteroids and long-acting beta-adrenergic
      agonists.
AB  - In summary, beta 2-adrenergic agonists and corticosteroids can interact to
      produce beneficial effects on airway function. The regular use of short-acting,
      beta 2-adrenergic agonists as relief therapy is safe and effective; however, some
      degree of caution may be required with the use of very high doses. Long-acting
      beta 2-adrenergic agonists provide further benefits in terms of asthma control in
      patients already established on inhaled corticosteroid therapy. The mechanism by
      which this interaction occurs remains to be elucidated, but may involve a
      protective effect of corticosteroids on dysfunctional beta-adrenergic receptor
      expression and function. In asthma, there may be a degree of uncoupling of the
      airway receptors, probably caused by cytokines such as IL-1 beta. However, this
      has not been established yet. Furthermore, beta-adrenergic receptor-mediated
      effects may be more quickly downregulated with beta-receptor stimulation, leading
      to a reduction in anti-inflammatory effects. The regular use of corticosteroids
      leads to an inhibition of cytokine production and prevents beta-adrenergic
      receptor downregulation, allowing beta 2-adrenergic agonists to be more
      effective. Further research, which may lead to a greater understanding of these
      mechanisms, may also lead to the development of more effective treatment
      regimens.

PMID- 9615841
TI  - The pharmacologic and clinical properties of Oxis (formoterol) Turbuhaler.
AB  - Oxis Turbuhaler has been approved for use in Europe at doses of 6, 12, or 24
      micrograms once or twice daily. It has a rapid onset of action (within minutes)
      and demonstrates a maintained effect on airway function (an improvement of 20-30
      l/min in PEF is seen 12 h after dosing), and it is well tolerated and safe. It
      decreases the incidence of acute asthma attacks, stimulates an immediate increase
      in PEF (in the order of 40-45 l/min), is effective when given in conjunction with
      anti-inflammatory medication, and has been shown to maintain a level of asthma
      control in all studies performed. Hence, Oxis Turbuhaler is a clinically relevant
      tool for use in patients receiving inhaled corticosteroids who require additional
      control of their asthma symptoms.

PMID- 9615842
TI  - Additive effects of inhaled formoterol and budesonide in reducing asthma
      exacerbations.

PMID- 9615843
TI  - [Intubating laryngeal mask. Positive early findings].

PMID- 9615844
TI  - [Hyperbaric oxygenation. An area for the anesthetist?].
AB  - Hyperbaric Oxygen (HBO) therapy is a kind of medical treatment in which a patient
      breathes 100% of oxygen inside a pressure chamber while the pressure of the
      chamber is increased to a point higher than sea level pressure. It is strongly
      based on clearly defined physical laws and physiological regularities. For the
      clinical use of HBO therapy, according to international recommendations, there
      are several commonly accepted indications in which HBO either is the only
      causative life-saving kind of treatment, or is an essential and oftenly decisive
      component of a comprehensive interdisciplinary intensive care therapy. Among
      potential adverse effects, barotrauma of the lungs and especially oxygen toxicity
      to the central nervous system have to be mentioned. Clinical use of HBO therefore
      requires special knowledge of its effects, risks, and adverse effects, a clear
      and distinct indication, and the ability and skills to keep complications under
      control by means of intensive care or emergency medical measures. The clinical
      use of hyperbaric oxygen with its interdisciplinary-like character of emergency
      medicine or intensive care therapy therefore should be an additional, most
      interesting field of activity for the anaesthesiologist.

PMID- 9615845
TI  - [Early signs of toxicity and "subtoxic" conditions in infant monitoring.
      Bupivacaine plasma levels following caudal anesthesia].
AB  - In order to evaluate whether caudal bupivacaine 3.1 mg/kg is associated with
      early central nervous system toxicity in awake infants, a clinical trial was
      performed. METHODS: After obtaining Local Ethical Committee approval and informed
      parental consent, seven awake infants (postconceptual age: 36-52 wks; weight: 2.2
      4.7 kg) received a caudal block with bupivacaine 3.1 mg/kg with epinephrine 5
      ug/ml in the left lateral position. Before performance of the caudal block a five
      minute EEG registration was performed, immediately followed by an assessment of
      the patient's clinical status based on a scoring system of following parameters:
      level of consciousness; muscular tone in upper extremities, tested by flexion and
      extension of the elbows; and the quality of the patient's cry in response to a
      skin pinch. Twenty minutes after the caudal block another EEG was performed and
      another assessment of the clinical status of the patient. After completion of the
      clinical assessment blood samples were collected for determination of plasma
      bupivacaine, albumin and alpha-1 acid glycoprotein concentrations. RESULTS: In
      six of seven infants the EEG pattern from the first to the second recording
      showed a shift of the general frequency spectrum towards a lower range. In two of
      these patients (No. 3 and 4) signs of pharmacologically induced antiepileptic
      effects (disappearance of sharp waves) were observed. Patients No. 2 and 6 showed
      signs of increased muscular activity and of suspect epileptic activity.
      Bupivacaine plasma concentrations ranged from 0.56-1.62 ug/ml, alpha-1 acid
      glycoprotein levels from 0.33-0.76 g/l and albumin levels from 25-38 g/l.
      DISCUSSION: In a few patients this systemic effect was clinically also associated
      with what is usually classified as early central nervous system toxicity. As a
      result of these findings the study was stopped prematurely, due to safety
      reasons. The low plasma levels of bupivacaine associated with side effects in
      this study may have two possible explanations. First, our patients did not
      receive any sedative drugs or anaesthetics that could have masked symptoms or
      have increased the threshold for systemic effects. Second, as can be expected in
      this age group plasma levels of alpha-1 acidglycoprotein were low. Thus, the
      lower plasma concentrations of total bupivacaine observed in the present study
      might have been associated with a similar unbound, free concentration of
      bupivacaine as it is seen in older children and adults at total plasma levels of
      2-4 ug/ml and at alpha-1 acidglycoprotein levels within the normal adult range.
      We conclude that Bupivacaine at 3 mg/kg is associated with systemic side effects
      in infants receiving awake caudal anaesthesia. Therefore we recommend to aim at a
      dose of not larger than 2 mg/kg in caudal blocks if no premedication or other
      sedative drugs are given simultaneously.

PMID- 9615846
TI  - [Prothrombin time and thromboplastin time. On-site measurement of the prothrombin
      time and activated partial thromboplastin time of surgical patients with laser
      photometry].
AB  - Turnaround time for analysis of prothrombin time (PT) and activated partial
      thromboplastin time (APTT) by standard laboratory methods ranges between 40 min
      and several hours. The delay in obtaining the test results limits their clinical
      utility for treatment of perioperative coagulation disorders and adequate anti
      coagulation therapy. In this study, we compared on-site coagulation testing (OCT)
      of whole blood, which takes about 3 min, with standard laboratory plasma
      coagulation tests by our institutional laboratory (LAB) to assess the accuracy of
      the OCT in a clinical setting (abdominal and postcardiac surgery). METHODS: PT of
      62 patients with abdominal surgery was measured intra- and postoperatively using
      both LAB (KC 40, Thromborel S, Centeon) and OCT (CoaguChek Plus, Boehringer
      Mannheim) systems. APTT was determined by LAB-(KC 40, Pathromtin, Centeon) and
      OCT-methods in 53 patients who underwent cardiac surgery requiring
      cardiopulmonary bypass. RESULTS: Linear regression demonstrated a strong and
      significant (p = 0.0001) correlation of OCT- and LAB-determinations both for PT
      (r = 0.92) and APTT (r = 0.91). For PT testing, bias analyses showed an agreement
      between OCT- and LAB-International Normalized Ratio (INR) (bias = 0.24; relative
      error = 14.6%) that was considered clinically acceptable, with 95% of the INR
      differences lying between -0,26 and +0,74 (mean +/- 2 SD). Although commercial
      APTT-reagents usually differ in their sensitivity to heparin, we also found an
      acceptable agreement between OCT- and LAB-APTT values (bias = 6.7 s +/- 22 s;
      mean +/- 2 SD; relative error = 12%). CONCLUSION: On-site coagulation monitoring
      provides a rapid, convenient, and accurate assessment of coagulation that can
      both guide specific anti-coagulation therapy and optimize therapy control of
      coagulation disorders after cardiac and abdominal operations. As a consequence,
      OCT offers a valuable tool to reduce the inappropriate use of fresh frozen plasma
      and to improve cost-effectiveness.

PMID- 9615847
TI  - [Randomized, double-blind study with ketoprofen in gynecologic patients.
      Preemptive analgesia study following the Brevik-Stubhaug design].
AB  - STUDY OBJECTIVE: The clinical effect of ketoprofen is based not only on the
      inhibition of prostaglandin synthesis. Ketoprofen also acts through kynurenic
      acid as a central antagonist on the NMDA receptor. Due to this central analgesic
      mechanism of ketoprofen, we expected an analgesic preemptive effect. This study
      was carried out following the Breivik/Stubhaug preemptive effect study design.
      METHODS: In 81 patients scheduled for gynaecological surgery a randomized double
      blind study was performed. Three groups were studied: Group I received
      preoperative ketoprofen 100 mg i.v., 12 mg/h during surgery and for 48 hours
      afterwards. Group II received 100 mg ketoprofen as a bolus injection before the
      end of surgery, thereafter 12 mg/h ketoprofen continuously for 48 hours. Group
      III received a placebo during surgery and for 48 hours after surgery. The effects
      were measured postoperatively using a visual analog scale (VAS; at rest and on
      exertion) and the total analgesic consumption (PCA piritramide) within the first
      48 hours after surgery. Furthermore, the time to first analgesic request was
      recorded. The vital signs and side effects were documented. RESULTS: The time to
      first analgesic request in group I was significantly longer than in groups II and
      III. In addition, the cumulative postoperative analgesic consumption during the
      first 24 hours after surgery was significantly lower in group I than in group
      III. Furthermore, the combination of an opioid with a non-opioid led to a lower
      pain score (VAS) at rest and on exertion. CONCLUSIONS: We showed a preemptive
      effect with ketoprofen, which was expressed significantly both in terms of the
      time to first analgesic request and by the lower analgesic consumption in the
      first 24 hours after surgery.

PMID- 9615848
TI  - [First experience with the laryngeal intubation mask].
AB  - OBJECTIVE: We report our initial experience with an improved model of the
      laryngeal mask airway, the intubating laryngeal mask airway (ILMA, commercial
      name Fastrach), which was designed by A.I.J. Brain to improve blind endotracheal
      intubation through a laryngeal mask. METHODS: In the ILMA, a number of
      construction details were newly designed compared to a standard laryngeal mask
      airway (SLM): 1) the angle between the shaft and the mask plane is changed, and
      also the radius of the shaft, 2) the internal diameter of the shaft is increased
      to allow the passage of an 8.0 mm cuffed endotracheal tube, resulting in an outer
      diameter of 2.0 cm, 3) a stable rubber lip (epiglottic elevating bar) is
      incorporated instead of the gills to clear the epiglottis out of the lumen during
      the passage of the endotracheal tube, 4) the shaft is manufactured out of
      stainless steel covered by silicone with a handle attached for more precise
      guidance. We prospectively used the ILMA in 80 patients for blind intubation. 51
      had normal anatomy (group I), 19 were difficult to intubate (Cormack grade 3-4;
      group II), 18 had a reduced mouth opening (< or = 2.5 cm awake; group III), 8 of
      them also were difficult to intubate. RESULTS: Insertion of the ILMA and
      ventilation was possible in all patients but one with a mouth opening of 1.3 cm
      during anaesthesia. 4 patients with difficult intubation and one with normal
      anatomy could not be ventilated with a face mask but could be ventilated with the
      ILMA. Blind intubation was successful in 69 out of 80 patients (global success
      rate 87%; group I: 84%; II: 95%; III: 83%), in 38 during the first attempt
      (initial success rate 48%; group I: 45%; II: 63%; III: 44%), showing no
      difference for patients with normal anatomy, difficult intubation or reduced
      mouth opening. For 82 successful intubations, 157 intubation attempts were
      performed (success rate per attempt 52%; group I: 48%; II: 67%; III: 54%).
      Success rate per attempt decreased to 42%, if intubation was not successful
      during the first attempt (106 intubation attempts resulting in 44 successful
      intubations, including 31 intubation attempts for 11 failures; group I: 35%; II:
      56%; III: 38%). Intubation through the ILMA was not possible in 11 patients
      (14%). Failures to intubate were caused by a reduced mouth opening in 1 patient,
      an unsuited endotracheal tube in 1 patient, a wrong size of the ILMA may have
      been the cause in 6 patients, in the remaining 3, lacking personal skill may have
      been responsible. Endotracheal tubes suited to be used with the ILMA are straight
      or preformed Woodbridge tubes, whereas standard plastic tubes are too stiff.
      Manouvres facilitating blind intubation though the ILMA were careful alignment of
      the ILMA with the handle, an up and down manouvre, rotation of the tube or head
      movements. CONCLUSION: The ILMA improved ventilation compared to a face mask and
      almost doubled the success rate of blind intubation compared to a SLM in our
      hands in a variety of intubation situations. The ILMA has the potential to be
      useful in difficult to intubate patients--except those with cervical pathology-
      or in emergency medicine. Handling can be trained during every day routine.
      Experienced judgement of definite endotracheal tube placement is mandatory.

PMID- 9615849
TI  - [New aspects of electric defibrillation].
AB  - Early defibrillation is the standard of care for patients with ventricular
      fibrillation (VF) and pulseless ventricular tachycardia (VT). Technical
      developments aim at further miniaturization and simplification of defibrillators
      as well as adaptation of energy requirements to the patient's needs. Implantable
      Cardioverter-Defibrillators (ICD) and automated external defibrillators (AED) are
      based upon the same technology. Both devices analyze the ECG signal internally,
      followed by a "shock" or "no shock" decision. Use of automated devices is the
      prerequisite for defibrillation by non-physicians. Chest impedance measurements
      and use of alternative shock waveforms, such as biphasic, aim at adaptation of
      energy or current to the patient's individual needs and avoid application of
      unnecessarily high amounts of energy to the myocardium. Calculation of median
      frequency is a non-invasive method for analyzing the heart's metabolic and
      electrical state. It helps to determine the optimal moment for defibrillation
      during cardiopulmonary resuscitation (CPR). Developments concerning the structure
      of in-hospital emergency systems or pre-hospital emergency medical services (EMS)
      aim at further reductions in time from collapse of a patient until first
      defibrillation. Such developments include early defibrillation programs for
      emergency medical technicians (EMT), nurses, and fire or police department first
      responders as well as wide distribution of easy-to-operate defibrillators in
      public areas, as discussed during the American Heart Association's Public Access
      Defibrillation conferences. All programs of that kind have to be organized and
      supervised by a physician who is responsible for training and supervision of the
      personnel involved.

PMID- 9615850
TI  - [Excessive tissue storage of colloids in the reticuloendothelial system].
AB  - In addition to renal elimination and gastrointestinal metabolism (amylase;
      splenic and hepatic dextranase) colloid plasma solutions like dextran and
      hydroxyethyl starch deposit in tissues, especially in the reticuloendothelial
      system (RES). This tissue storage is limited in time (weeks to months), is
      influenced by the employed solution and other factors (lysosomes) and has usually
      no clinical importance (no RES blockade). We report here a case study of a
      patient with sepsis (lung, liver and kidney failure) who had an overload of the
      RES with colloids while being treated with dextran (molecular weight 40,000 and
      70,000 daltons) and hydroxyethyl starch (mw 450,000 daltons, molar substitution
      0,7) for 5 weeks. Autopsy showed parenchymal and reticuloendothelial cells of
      liver, lung, kidney and spleen with a large amount of colloid mass inclusions and
      altered organ morphology. This storage may have impaired ventilation, transport
      of bile acids and renal function. A possible role of tissue storage of colloids
      in organ failure is discussed.

PMID- 9615851
TI  - [Can sevoflurane save time in routine clincal use? A comparison with halothane in
      pediatric anesthesia].
AB  - The volatile agent sevoflurane enables a rapid emergence from anaesthesia. The
      aim of this study was to investigate the possibility of increasing turnover in
      pediatric anaesthetic cases by use of sevoflurane in comparison with halothane.
      Often short cases or day cases need rapid turnover. METHODS AND PATIENTS: The
      pediatric patients aged 4-14 years (ASA I) presenting for elective ophthalmic
      surgery were randomised to either the halothane or the sevoflurane group.
      Standard monitoring was applied to all patients, in addition the pEEG was used to
      determine comparable anaesthetic depth. Sevoflurane or halothane were titrated to
      a SEF 90 of 8-12 Hz. Management of the airway was done with the RLMA (reinforced
      laryngeal mask). All patients were under controlled ventilation. At the end of
      surgery and anaesthesia 3 time intervals were measured: phase I) end of
      anaesthetic application--start of spontaneous respiration; phase II) start of
      spontaneous respiration--removal of RLMA. The SEF 90 interval was also assessed.
      RESULTS: 18 cases were included (halo n = 8/sevo n = 10, no significant
      differences concerning weight, age, anaesthesia time). There is a significant
      advantage for the Sevoflurane group in phase II of 6.8 minutes. No differences
      were seen in phase I and SEF 90 interval. CONCLUSION: Sevoflurane offers the
      potential for shortening turnover in pediatric anaesthesia.

PMID- 9615852
TI  - [Intraoperative administration of calcium. Physiology--physiopathology--clinical
      indications].

PMID- 9615853
TI  - [Status quo in "anesthesiology"? American Society of Anesthesiologists 1997
      annual meeting--San Diego, October 18-22, 1997].

PMID- 9615854
TI  - [Outcome following intensive care].

PMID- 9615856
TI  - [Reply to the remarks of S.-M. Kasper].

PMID- 9615855
TI  - [Methods for reduction of homologous blood transfusion in operative medicine.
      Remarks on the work of O. Habler and K. Messmer. Anaesthesist (1997) 46:915-926].

PMID- 9615857
TI  - [Remifentanil in the rescue service].

PMID- 9615858
TI  - [Low flow anesthesia with the anesthesia respirator Ventilog 2].

PMID- 9615859
TI  - Radiological protection policy for the disposal of radioactive waste. Adopted by
      the Commission in May 1997. The International Commission on Radiation Protection.

PMID- 9615860
TI  - From the pigments of the actinomycetes to third generation antitumor
      anthracyclines.
AB  - After the assessment of the antitumor activity of the anthracycline pigments, the
      S peucetius group of metabolites was discovered and eventually doxorubicin, a
      major anticancer agent of established clinical usefulness was developed in the
      early seventies. A second generation of compounds followed, represented mainly by
      the better tolerated epirubicin and by the highly potent antileukemic drug,
      idarubicin. This was the result of a wide program of analog development that
      provided the basis for further investigations concerning both the study of
      structure-activity relationships and the synthesis of novel promising derivatives
      including the 8- and 10-fluoro compounds and the disaccharides. A member of the
      latter group, namely 7-O-(4'-O-alpha-L-daunosaminyl-2'-deoxy- alpha-L-fucosyl)-4
      demethoxyadriamycinone, is undergoing clinical trials as a third generation
      antitumor anthracycline.

PMID- 9615861
TI  - Discovery of podophyllotoxins.
AB  - This review deals with the historical discovery of particularly important lignan
      derivatives used in cancer chemotherapy. From isolation of the naturally
      occurring podophyllotoxin, an inhibitor of microtubule assembly, to hemisynthesis
      of the clinically important anticancer drugs etoposide and teniposide, it will be
      demonstrated how the activities and the ability of this class of compounds to
      inhibit topoisomerase II were discovered by different research teams. By virtue
      of these discoveries, new hemisynthetic derivatives, with different mechanisms of
      action, are bringing improvements in the ability to treat cancer.

PMID- 9615862
TI  - The mapping of DNA topoisomerase sites in vivo: a tool to enlight the functions
      of topoisomerases.
AB  - The possibility to record a trace of the precise sites of topoisomerase action
      has been exploited for almost 12 years in many laboratories. The large majority
      of the studies were performed in vitro, giving a good picture of sequence
      specificities of topoisomerases, and of the preference of various drugs for some
      sequences. Only a relatively small number of reports concern in vivo studies.
      Their main conclusions are the following: i) topoisomerase II sites are often
      found near replication origins and termini, where they are supposed to play a
      role in the decatenation of daughter DNA molecules, and possibly in the
      initiation of replication; ii) topoisomerase II sites are found in the promoter
      region of many genes, but they seem related to the condensation state of
      chromatin in this region, rather than to transcription per se; iii) some
      topoisomerase II sites, resistant to high salt, are found in or near matrix
      associated regions (MARs), suggesting a role in loop anchorage or (and) in the
      control of topology of individual chromatin loops; iv) topoisomerase I sites
      appear less localized, acting all along the transcription units, where they seem
      directly involved in transcription; and v) topoisomerase I sites are possibly
      connected with replication fork progression and (or) with the termination of
      replication. Despite these advances, the precise role of topoisomerases in vivo
      is still poorly understood, especially in recombination and chromatin
      condensation and decondensation during the cell cycle. Future attempts should
      take into account the possible specialization of the multiple topoisomerases
      found in a given cell, and the use of highly synchronized systems.

PMID- 9615863
TI  - Bis(2,6-dioxopiperazines), catalytic inhibitors of DNA topoisomerase II, as
      molecular probes, cardioprotectors and antitumor drugs.
AB  - Bis(2,6-dioxopiperazines) and other catalytic inhibitors of mammalian DNA
      topoisomerase II have recently been found in natural and synthetic compounds.
      These compounds target the enzyme within the cell and inhibit various genetic
      processes involving the enzyme such as DNA replication and chromosome dynamics
      and thus proved to be good probes for the functional analyses of the enzyme in a
      variety of eucaryotes from yeast to mammals. Catalytic inhibitors were shown to
      be antagonists against topoisomerase II poisons under some conditions, but to be
      synergistic under others. Bis(2,6-dioxopiperazines) have a potential to overcome
      cardiac toxicity caused by potent antitumor anthracycline antibiotics such as
      doxorubicin and daunorubicin. ICRF-187, +enantiomer of racemic ICRF-159, has been
      used in EU countries as cardioprotector in cancer clinics. Furthermore, bis(2,6
      dioxopiperazines) enhance the efficacy of antitumor topoisomerase II poisons,
      e.g. anthracycline antibiotics such as daunorubicin and doxorubicin, by reducing
      their side effects and by allowing dose escalation of the antitumor drugs in
      preclinical and clinical settings. Besides bis(2,6-dioxopiperazines) per se
      having antitumor activity, and one of their derivatives, MST-16 or sobuzoxane,
      bis(N1-isobutyloxycarbonyloxymethyl-2,6-dioxopiperazine), has been developed in
      Japan and used in clinics as anticancer drug for malignant lymphomas and adult T
      cell leukemia (ATL). Further developments of bis(2,6-dioxopiperazines) as
      antimetastatic agents are expected.

PMID- 9615864
TI  - Drug resistance to topoisomerase II inhibitors.
AB  - We describe in this review the mechanisms of resistance to topoisomerase II
      inhibitors that have been identified in cell lines rendered resistant to drugs.
      They concern especially both quantitative and qualitative alterations of
      topoisomerase II, leading to drug insensitivity of the cells. Expression and
      activity of topoisomerase II have also been studied in a number of tumor
      specimens originating from patients, but the role of topoisomerase II alterations
      in drug resistance in the clinical setting has not yet been firmly established.
      It would be worthwhile, however, to develop predictive assays for drug activity
      in human cancers, based upon the topoisomerase II status of tumor samples.

PMID- 9615865
TI  - Diversity of DNA topoisomerases I and inhibitors.
AB  - The present review first describes the different type I topoisomerases found in
      eukaryotic cells: nuclear topoisomerase I (top1), topoisomerase 3 (top3),
      mitochondrial topoisomerase I and viral topoisomerases I. The second part of the
      review provides extensive information on the topoisomerase I inhibitors
      identified to date. These drugs can be grouped in two categories: top1 poisons
      and top1 suppressors. Both inhibit enzyme catalytic activity but top1 poisons
      trap the top1 catalytic intermediates ('cleavage complexes') while top1
      suppressors prevent or reverse top1 cleavage complexes. The molecular
      interactions of camptothecin with the top1 cleavage complexes are discussed as
      well as the mechanisms of selective killing of cancer cells.

PMID- 9615866
TI  - Preclinical development of camptothecin derivatives and clinical trials in
      pediatric oncology.
AB  - Although the prognosis of childhood cancers has dramatically improved over the
      last three decades, new active drugs are needed. Camptothecins represent a very
      attractive new class of anticancer drugs to develop in paediatric oncology. The
      preclinical and clinical development of two of these DNA-topoisomerase I
      inhibitors, i.e. topotecan and irinotecan, is ongoing in paediatric malignancies.
      Here we review the currently available results of this evaluation. Topotecan
      proved to be active against several paediatric tumour xenografts. In paediatric
      phase I studies exploring several administration schedules, myelosuppression was
      dose-limiting. The preliminary results of topotecan evaluation in phase II study
      showed antitumour activity in neuroblastoma (response rate: 15% at relapse and
      37% in newly diagnosed patients with disseminated disease) and in metastatic
      rhabdomyosarcoma (40% in untreated patients). Topotecan-containing drug
      combinations are currently investigated. Irinotecan displayed a broad spectrum of
      activity in paediatric solid tumour xenografts, including rhabdo-myosarcoma,
      neuroblastoma, peripheral primitive neuroectodermal tumour, medulloblastoma,
      ependymoma, malignant glioma and juvenile colon cancer. For several of these
      histology types, tumour-free survivors have been observed among animals bearing
      an advanced-stage tumour at time of treatment. The clinical evaluation of
      irinotecan in children is ongoing. Irinotecan undergoes a complex in vivo
      biotransformation involving several enzyme systems, such as carboxylesterase,
      UDPGT and cytochrome P450, in children as well as in adults. Preclinical studies
      of both drugs have shown that their activity was schedule-dependent. The optimal
      schedule of administration is an issue that needs to be addressed in children. In
      conclusion, the preliminary results of the paediatric evaluation of camptothecin
      derivatives show very encouraging results in childhood malignancies. The
      potential place of camptothecins in the treatment of paediatric malignant tumours
      is discussed.

PMID- 9615867
TI  - Physical activity, muscle, and the HSP70 response.
AB  - Selye (1936) described how organisms react to various external stimuli (i.e.,
      stressors). These reactions generally follow a programmed series of events and
      help the organism adapt to the imposed stress. The heat shock response is a
      common cellular reaction to external stressors, including physical activity. A
      characteristic set of proteins is synthesised shortly after the organism is
      exposed to stress. Researchers have not determined how heat shock proteins affect
      the exercise response. However, their role in adaptation to exercise and training
      might be inferred, since the synthetic patterns correlate well with the stress
      adaptation syndrome that Selye described. This review addresses the 70 kilodalton
      heat shock protein family (HSP70), the most strongly induced heat shock proteins.
      This paper provides an overview of the general heat shock response and a brief
      review of literature on HSP70 function, structure, regulation, and potential
      applications. Potential applications in health, exercise, and medicine are
      provided.

PMID- 9615868
TI  - Incomplete muscle activation after training with electromyostimulation.
AB  - Training with voluntary or electromyostimulation (EMS)-evoked eccentric
      contractions should produce complete muscle activation, since EMS and eccentric
      contractions preferentially recruit large motor units. Subjects (22 women ages 18
      40) were randomly assigned to a voluntary (VOL; n = 8), EMS (n = 8), or control
      group. VOL and EMS groups trained the quadriceps at the same, increasing force
      levels 4 times/week for 6 weeks using voluntary or EMS-evoked eccentric
      contractions. VOL improved voluntary more than EMS-evoked eccentric strength. EMS
      improved EMS-evoked strength more than voluntary. EMS training improved EMS
      evoked eccentric strength more than VOL training improved voluntary eccentric
      strength. EMS-evoked to voluntary force ratio increased from 0.57 (+/- 0.11) to
      1.20 (+/- 0.35) in EMS and did not change in VOL (all changes p < .05). Six of
      eight EMS subjects produced greater EMS-evoked force posttraining, suggesting
      incomplete muscle activation after EMS training.

PMID- 9615869
TI  - Effect of a sports food bar on fat utilisation and exercise duration.
AB  - The manufacturer claims that using the Access Fat Conversion Activity Bar
      increases fat utilisation, which would have a glycogen-sparing effect and delay
      the onset of fatigue from endurance exercise. This claim was tested using seven
      trained distance runners who performed two trials of treadmill running at 73% of
      VO2max to exhaustion. In a counterbalanced design, subjects ingested either one
      Access Bar with water or water only prior to treadmill running. Times to
      exhaustion for the control and Access treatment trials were 104.6 +/- 24.9 min
      and 93.9 +/- 21.4 min, respectively, and were not significantly different (p >
      .05). Differences between trials were not observed for the respiratory exchange
      ratio, blood lactate or glucose concentrations, plasma glycerol concentration, or
      perceived exertion. Based on results from this study, it was concluded that the
      Access Bar does not affect fat or carbohydrate utilisation and does not improve
      exercise endurance.

PMID- 9615870
TI  - Effect of energy restriction on muscle function and calcium stimulated protease
      activity in recreationally active women.
AB  - The purpose of this study was to investigate whether changes in substrate
      oxidation that are caused by energy restriction influenced muscle function and
      skeletal muscle calcium stimulated protease activity in female athletes.
      Endurance athletes were randomly assigned to maintenance energy (100% kcal) or
      energy restricted (75% kcal) diet treatment groups for 14 days while maintaining
      regular activity. Body weight significantly decreased in the 75% diet group (-1.7
      +/- 0.3 kg; p < .05), while fat oxidation increased (p < .05). Minimal changes in
      quadriceps function (assessed using the Kin/Com isokinetic dynamometer) were
      observed following diet treatment, except selected loss of muscle function in the
      75% diet group at a movement velocity of 120 deg/s. These results suggest that
      increased fat oxidation that is induced by an acute energy restriction does not
      promote loss of general muscle function and activation of calcium-sensitive
      muscle proteases.

PMID- 9615871
TI  - Thyroid hormone concentrations and muscle metabolism in amenorrheic and
      eumenorrheic athletes.
AB  - The relationship between resting thyroid hormone concentrations and exercise
      muscle metabolism was examined among eumenorrheic endurance-trained (n = 11),
      amenorrheic endurance-trained (n = 8), and eumenorrheic nonathletic (n = 13)
      subjects. Muscle metabolism was assessed with 31Phosphorous magnetic resonance
      spectroscopy by measuring changes in phosphocreatine (PCr), inorganic phosphate
      (Pi), and pH during plantar flexion exercise and recovery. All groups had similar
      Pi/PCr ratios and pH changes during exercise. Eumenorrheic endurance-trained
      subjects had faster recovery rates for PCr and Pi/PCr following exercise compared
      to the nonathletes (p < .05) and faster recovery rates for PCr compared to
      amenorrheic subjects (p < .05). Thyroxine (T4) and triiodothyronine (T3) levels
      were significantly lower in amenorrheic subjects compared to both eumenorrheic
      groups (p < .05). It was concluded that routine training enhances muscle
      metabolism, as measured by phosphate recovery kinetics. This enhancement was not
      evident in amenorrheic athletes with reduced T3 and T4 concentrations.

PMID- 9615872
TI  - Metabolic and hormonal responses to exercise in partially hepatectomised rats.
AB  - To characterise how the liver affects metabolic and hormonal exercise responses,
      hepatectomised (70%; HX) rats were submitted to a 30- or 50-min treadmill
      exercise (26 m/min, 0% slope) 48 hr or 7 days after surgery (reduced or normal
      liver mass, respectively). To determine whether metabolic effects of liver mass
      reduction during exercise were caused by reduced capacity of the liver to produce
      glucose, metabolic and hormonal responses to the same exercise protocol were
      measured in 48-hr HX rats. Euglycemia, maintained by exogenous glucose infusion,
      produced attenuated lactate, insulin, and glucagon values in 48-hr HX rats but
      did not affect FFA, glycerol, and plasma catecholamine responses. Results
      indicate that metabolic and hormonal exercise responses are amplified in 48-hr HX
      rats. Maintaining euglycemia in 48-hr HX rats during exercise does not reduce all
      responses. Intrahepatic events, similar to those in a short-term (48-hr) HX
      liver, may influence metabolic and hormonal exercise responses.

PMID- 9615873
TI  - Iodine staining for early endoscopic detection of esophageal cancer in
      alcoholics.
AB  - BACKGROUND AND STUDY AIMS: A retrospective epidemiological investigation has
      demonstrated that alcohol abuse is a major risk factor for esophageal cancer.
      However, prospective endoscopic screening for early detection in heavy drinkers
      is not available at present. PATIENTS AND METHODS: A prospective study was
      conducted that included 255 alcoholics (aged 52 +/- 9 years). The patients were
      consecutively screened using esophagoscopy with iodine staining and targeted
      biopsy. The study also explored whether there was a relationship between the
      amount of alcohol intake and the detection rate of esophageal cancer. RESULTS:
      Unstained lesions (larger than 5 mm) were observed on the esophageal wall in 55
      patients (21.6%). Ten patients (3.9%) with 13 lesions were found to have
      esophageal cancer of the superficial type, with no symptoms. Cancer invasion was
      confined to the epithelium in three patients, to the lamina propria in seven, and
      to the submucosa in three. There was a direct relationship between substantial
      alcohol intake and the presence of esophageal cancer. CONCLUSION: Screening
      esophagoscopy with iodine staining is very advantageous in detecting esophageal
      cancer at an early stage.

PMID- 9615875
TI  - Palliation of malignant gastric and small intestinal strictures with self
      expandable metal stents.
AB  - BACKGROUND: Malignant gastrointestinal obstruction is a common preterminal event
      that is often treated surgically. The use of self-expandable stents to treat
      malignant gastric and small intestinal strictures is limited. We evaluated the
      feasibility, effectiveness, safety and outcome of self-expandable metal stents in
      providing palliative care for patients with inoperable malignant strictures of
      the stomach and small intestine. METHODS: Eleven consecutive patients with
      complete or near complete gastric or small intestinal obstruction were treated
      palliatively with self-expandable metal stents. Contrast radiographs were taken
      before and after insertion in all patients to confirm patency. Nineteen stents
      were placed using biliary guidewires and catheters under endoscopic and
      fluoroscopic guidance. Diets were modified as needed. Success was defined both
      technically and clinically. RESULTS: Technical and clinical success with
      improvement in the patient's oral diet was achieved in ten patients (91%). The
      one failure was caused by severe anastomotic angulation and distal luminal
      obstruction. During the follow-up of 5 to 294 days (mean 77 days) there were no
      major complications except that the stents occluded in four patients. CONCLUSION:
      Palliation of malignant gastric and small intestinal strictures with self
      expandable metal stents is a feasible, effective, and safe alternative to
      operation.

PMID- 9615874
TI  - Photodynamic therapy of early squamous cell carcinomas of the esophagus: a review
      of 31 cases.
AB  - BACKGROUND AND STUDY AIMS: Patients with cancers of the head and neck have a
      strong tendency to develop early synchronous and metachronous carcinomas of the
      esophagus. In many of these patients, whose general condition is poor as a result
      of alcohol and tobacco abuse, the second primary cancers require minimally
      invasive treatment. The aims of this study were to evaluate the efficacy of
      photodynamic therapy for the treatment of early esophageal carcinomas and to
      compare the results obtained with three different photosensitizers
      (hematoporphyrin derivative), porfimer sodium (Photofrin II), and meta
      (tetrahydroxyphenyl)chlorin (m-THPC). PATIENTS AND METHODS: Thirty-one early
      squamous cell carcinomas (Tis or T1a) of the esophagus were treated by
      photodynamic therapy in 24 patients. Nine tumors were treated with
      hematoporphyrin derivative, eight with Photofrin II and 14 with m-THPC. RESULTS:
      The early cancers were cured in 84% of patients after a mean follow-up period of
      2 years. Because the number of cases included in each group was small, the
      differences in recurrence rates for the different photosensitizers could not be
      evaluated statistically, but m-THPC was more phototoxic, induced a shorter period
      of photosensitization of the skin, and had better selectivity than either of the
      other photosensitizers. There were four major complications: two stenoses and two
      esophagotracheal fistulas. CONCLUSIONS: Photodynamic therapy eradicates early
      squamous cell carcinomas (Tis and T1a) of the esophagus efficiently. Transmural
      necroses leading to fistulas can be avoided by using a low-penetrating wavelength
      of laser light (green light at 514.5 m instead of red light at 630 or 652 nm).
      Stenoses always result from circumferential irradiation of the esophageal wall,
      and this can be avoided by using a 180 degrees or 240 degrees windowed
      cylindrical light distributor.

PMID- 9615876
TI  - Is pancreatoscopy of any benefit in clarifying the diagnosis of pancreatic duct
      lesions?
AB  - BACKGROUND AND STUDY AIMS: Modern fine-caliber endoscopes enable clinicians to
      directly visualize the pancreatic duct. They allow intraductal manipulation under
      optical control. We tried to evaluate the additional diagnostic potential of
      pancreatoscopy in assessing inconclusive intraductal pancreatic changes. PATIENTS
      AND METHODS: We prospectively performed 20 pancreatoscopies in 18 patients with
      inconclusive ductal abnormalities that had been previously investigated by
      computed tomography (CT) scan, abdominal ultrasound and endoscopic retrograde
      cholangiopancreatography (ERCP). The CHF-BP 30 (Olympus Optical Co., Japan)
      endoscope with an outer diameter of 3.1 mm and an instrumentation channel of 1.2
      mm was used. Biopsies, cytological brushing and fluid collection were carried
      out, and the site of ductal abnormality was visualized. Endoscopic sphincterotomy
      (EST) was carried out in every patient prior to insertion of the pancreatoscope.
      RESULTS: Seven intraductal tumors were histologically confirmed, i.e. five
      intraductal papillary mucinous tumors and two adenocarcinomas. Benign appearance
      of the intraductal lesion plus negative histopathological examinations were
      confirmed by a follow-up of two years in eight patients. Five had chronic
      pancreatitis, and a further three had pancreatitis with strictures, blood clot
      obstruction, and idiopathic benign stricture, respectively. There were no
      complications with the exception of one bleeding episode after EST; no
      pancreatitis occurred. CONCLUSIONS: Pancreatoscopy is of diagnostic value in
      addition to CT, transabdominal ultrasound and ERCP in the differential diagnosis
      of poorly defined pancreatic lesions, particularly when assessing alterations of
      the ductal caliber without parenchymatous lesions.

PMID- 9615878
TI  - Percutaneous transhepatic cholelithotripsy for difficult common bile duct stones.
AB  - BACKGROUND AND STUDY AIMS: A study was carried out to assess the feasibility of a
      new rapid technique for percutaneous transhepatic access to the biliary tract
      with endoscopic lithotripsy (percutaneous transhepatic cholelithotripsy).
      PATIENTS AND METHODS: 14 patients with biliary stones resistant to endoscopic
      retrograde cholangiography and extracorporeal shock wave lithotripsy underwent
      cholelithotripsy, utilizing a new dilation kit with massive teflon dilators
      covered by "peel-away sheets". RESULTS: Successful lithotripsy was performed in
      all patients by laser lithotripsy through a choledochoscope or ureteroscope in
      ten patients and by stone removal by basket in the remaining four patients. The
      procedure was carried out using local anesthesia in the last 11 patients. Except
      for two patients with transient cholangitis, no complications occurred.
      CONCLUSIONS: Difficult bile duct and intrahepatic stones can be treated
      successfully with a simple percutaneous transhepatic cholelithotripsy procedure
      including local anesthesia, dilation and stone clearance.

PMID- 9615877
TI  - Limitations of percutaneous transhepatic cholangioscopy for the diagnosis of the
      intramural extension of bile duct carcinoma.
AB  - BACKGROUND AND STUDY AIMS: Vascular dilatation seen on percutaneous transhepatic
      cholangioscopy (PTCS) is diagnostic of intramural invasive carcinoma of the bile
      duct, but the limitations of the technique, including biopsy, for the diagnosis
      of intramural extension of bile duct carcinoma have not to our knowledge been
      investigated before. The aims of the present study were to estimate the thickness
      of the specimens of bile duct wall taken by biopsy, to assess the sensitivity of
      PTCS for detecting intramural invasive carcinoma, and to identify the
      characteristics of the intramural extension of bile duct carcinoma associated
      with vascular dilatation. PATIENTS AND METHODS: A total of 135 biopsy, and 16
      surgical specimens obtained from 25 bile duct carcinomas were examined for: the
      thickness of the biopsy specimens and of the mucosa and combined mucosal
      fibromuscular layers in the resected common bile ducts and common hepatic ducts;
      the presence of muscular and neural bundles in the biopsy specimens; the number
      of invasive carcinomas in the biopsy specimens that had been taken from stenosed
      regions; and the relation between intramural extension of invasive carcinoma and
      vascular dilatation. RESULTS: The mean thickness of the biopsy specimens did not
      differ from the mean thickness of the mucosa in the resected specimens, but was
      significantly lower than that of the combined mucosa and fibromuscular layer.
      Muscular bundles were included in only 13 (14%) of the biopsy specimens, and
      there were no neural bundles. Carcinomas and invasive carcinomas were diagnosed
      histologically from the biopsy specimen in 96% and 91% of the cases,
      respectively. The sensitivity of a single biopsy for diagnosis for invasive
      carcinoma in stenosed regions was 62%, almost the same as the sensitivity in non
      stenosed regions with vascular dilatation (68%). On histologic examination of 16
      resected specimens, the sensitivity and specificity of vascular dilatation as a
      marker of the intramural extension of an invasive carcinoma were 39% and 100%,
      respectively, and this was significantly more common in invasive carcinomas that
      were invading the mucosa beyond the adventitia than in those limited to the
      adventitia. CONCLUSION: Histologic examinations of specimens obtained by PTCS
      guided biopsy can detect invasive carcinoma in only the superficial layers of the
      bile duct, such as the mucosa and the shallowest fibromuscular layer. Multiple
      specimens are needed for the diagnosis of invasive carcinoma because the
      sensitivity of examination of a single specimen for detecting invasive carcinoma
      is low. Vascular dilatation is characteristic of carcinoma that is invading the
      mucosa beyond the adventitia, so the diagnosis of intramural extension of bile
      duct carcinoma limited to the adventitia, particularly if it has spread to the
      deeper fibromuscular layer and the adventitia, is difficult to make by PTCS.

PMID- 9615879
TI  - Action of pure ethanol and some alcoholic beverages on the gastric mucosa in
      healthy humans: a descriptive endoscopic study.
AB  - BACKGROUND AND STUDY AIMS: The action of ethanol and alcoholic beverages on the
      gastric mucosa in healthy humans is largely unknown. This study was designed to
      compare the effects of beer, white wine, whisky, and the comparable pure ethanol
      solutions on the gastric and duodenal mucosa in a controlled, randomized, double
      blind endoscopic investigation. MATERIALS AND METHODS: In 47 healthy human
      volunteers, 100 ml of beer, or white wine, or whisky, or a comparable pure
      ethanol solution (4%, 10%, 40% vol/vol), or isotonic saline as a control, were
      sprayed on the antral mucosa. The endoscopic appearance of the gastric and
      duodenal mucosa was assessed before, immediately after, and 30, 60, 240 minutes
      and 24 hours after instillation. The lesions were scored using an endoscopic
      grading system (0-5; 0 = normal mucosa and 5 = ten or more hemorrhagic lesions).
      RESULTS: Pure ethanol damaged the gastric mucosa in a dose-dependent fashion. The
      lesions occurred within 30 minutes, and reached a maximum after 60 minutes
      (antral score for 4% = 1.3; 10% = 1.8; 40% 3.8; control = 1.5). Beer, wine and
      whisky also induced gastric mucosal injury, but to a lesser extent than the
      comparable ethanol solutions. The 24-hour integrated endoscopic scores for beer
      and wine were significantly lower (P < 0.05) than the corresponding ethanol
      content. In the case of pure ethanol > 10% and whisky, the lesions were still
      present 24 hours later (antral score for 10% = 1.5; 40% = 2.0; whisky = 2.3;
      control = 0). No lesions were observed in the duodenum. None of the volunteers
      reported any abdominal pain during the whole investigation. CONCLUSIONS:
      Intragastric application of 4%, 10%, and 40% vol/vol pure ethanol induces
      gastric, but not duodenal, mucosal lesions in a dose-dependent fashion. Beer,
      white wine, and whisky induce gastric mucosal lesions to a lesser degree than the
      corresponding ethanol content. Lesions induced by higher ethanol concentrations
      (> 10%) and whisky take more than 24 hours to heal. The lesser damage caused by
      alcoholic beverages may be due to the protective action of unknown nonalcoholic
      ingredients.

PMID- 9615880
TI  - Endoscopy as a research vehicle: potentials and pitfalls.

PMID- 9615881
TI  - Should therapeutic ERCP be conducted in special circumstances without
      fluoroscopy? Pro.

PMID- 9615882
TI  - Should ERCP be conducted in special circumstances without fluoroscopy? Contra.

PMID- 9615883
TI  - Four things to recall about esophageal cancer.

PMID- 9615884
TI  - Endoscopic papillotomy without fluoroscopy in pregnancy.

PMID- 9615885
TI  - Pancreatico-pleural fistula.

PMID- 9615886
TI  - Intussusception of the rectum mimicking rectal tumor on endoscopy.

PMID- 9615887
TI  - Ascaris pancreatitis: early diagnosis by ultrasonography and endoscopic
      treatment.

PMID- 9615888
TI  - Guidelines of the European Society of Gastrointestinal Endoscopy (E.S.G.E.)
      antibiotic prophylaxis for gastrointestinal endoscopy. European Society of
      Gastrointestinal Endoscopy.
AB  - There are two situations when antibiotic prophylaxis is recommended. The first is
      associated with procedures known to be followed by high rates of bacteraemia,
      involving organisms prone to cause endocarditis. These include oesophageal
      dilatation, variceal sclerotherapy and laser therapy in the upper
      gastrointestinal tract. As bacteraemia following these procedures is usually
      harmless in average risk patients antibiotic prophylaxis is recommended only for
      a patient with a lesion susceptible to endocarditis or one who is at increased
      risk of symptomatic bacteraemia due to neutropenia or immunosuppression. In most
      cases parenteral amoxycillin and gentamicin is recommended plus metronidazole for
      neutropenic patients. Vancomycin or teicoplanin replace amoxycillin in a case of
      allergy. The second situation concerns procedures with a high incidence of local
      infection or which may lead to serious sepsis. These include therapeutic
      retrograde cholangiopancratography and percutaneous endoscopic gastrostomy where
      antibiotic prophylaxis is recommended even in average risk patients. Several
      antibiotics are recommended including oral ciprofloxacin or parenteral gentamicin
      or quinolone for ERCP and amoxycillin for PEG or cephalosporin or
      ureidopenicillin for both.

PMID- 9615889
TI  - A mouthguard for endoscopic examination of patients with oral submucous fibrosis
      and ankylosis of the temporomandibular joint.

PMID- 9615890
TI  - Multiple mucosal bridge formation in the esophagus in a patient with Crohn's
      disease.

PMID- 9615891
TI  - Esophageal involvement by Hodgkin's disease mimicking submucosal tumor.

PMID- 9615892
TI  - Treatment of bleeding gastric varices with tissue adhesive (Histoacryl) in
      children.

PMID- 9615893
TI  - Dried bay leaf: an unusual cause of upper gastrointestinal tract hemorrhage.

PMID- 9615894
TI  - Poly-N-acetyl glucosamine: will it replace cyanoacrylate for treatment of gastric
      varices? A pilot study in a rabbit model.

PMID- 9615895
TI  - A bevelled tube slide on a fiberoptic gastroscope for removal of a dental
      prosthesis from the esophagus.

PMID- 9615896
TI  - Endoscopic ultrasonography of a pancreatic lymphoma.

PMID- 9615897
TI  - Endoscopic balloon dilation of ileal stricture due to tuberculosis.

PMID- 9615898
TI  - Massive pneumoperitoneum after endoscopic argon plasma coagulation.

PMID- 9615899
TI  - Health effects of trans fatty acids.

PMID- 9615900
TI  - Erythrocyte membrane thiol proteins associated with changes in the kinetics of
      Na/Li countertransport: a possible molecular explanation of changes in disease.
AB  - BACKGROUND: Abnormal erythrocyte Na/Li countertransport is associated with
      diseases such as essential hypertension and diabetic renal disease. Although it
      seems unlikely that Na/Li countertransport contributes to any disease process, it
      may be abnormal because of a change in the cell membrane that is part of the
      disease process. METHODS: We have shown that Na/Li countertransport kinetics are
      modified by two types of thiol group. One of these, which we have called 'type
      1', is rapidly alkylated by N-ethylmaleimide to give a kinetic pattern similar to
      that in the above diseases. RESULTS: AtpH 6 and 2 degrees C, both N
      ethylmaleimide and iodoacetamide cause the K(m) of Na/Li countertransport to
      decrease to completion in 300s, with 78% (SEM 6%) of the decrease occurring in
      30s. Using these reaction conditions, N-ethylmaleimide reacted with a unique
      thiol group on a 33-kD protein, blocking its subsequent reaction with biotin
      maleimide. This 33-kD protein was present in rabbit erythrocytes, which have high
      levels of Na/Li countertransport, but absent from rat erythrocytes, which have no
      Na/Li countertransport. Iodoacetyl biotin labelled a 60-kD protein that was
      specifically blocked by iodoacetamide. CONCLUSION: We suggest that these proteins
      are members of a cluster of membrane proteins that can modify Na/Li
      countertransport and may have a functional role in the disease processes.

PMID- 9615901
TI  - Effect of thyroid hormone on plasma apolipoproteins and apoA- and apoB-containing
      lipoprotein particles.
AB  - METHODS: Apolipoprotein and apoB- and apoA-containing lipoprotein particle
      concentrations were determined in 10 athyreotic patients 4 weeks after withdrawal
      of Synthroid replacement therapy [T4, 0.96 +/- 0.66 microgram mL-1; thyroid
      stimulating hormone (TSH), 62.7 +/- 22.8 muIU mL-1] and again 4 weeks after
      reinstitution of treatment. RESULTS: Thyroid hormone replacement was associated
      with significant decreases in plasma cholesterol (TC), triglyceride (TG),
      apolipoprotein B and apolipoprotein C-III (P < 0.01). Both the cholesterol ester
      rich LP-B particles and triglyceride-rich LP-Bc particles declined significantly
      in response to thyroid hormone (LP-B withdrawal 81.6 +/- 24.0 vs. replacement
      65.1 +/- 22.0; LP-Bc withdrawal 14.3 +/- 6.0 vs. replacement 10.9 +/- 4.8 mg%, P
      < 0.01). ApoC-III also decreased in high-density lipoprotein (HDL) (apoC-III-HS),
      and in very low-density lipoprotein (VLDL) + low-density lipoprotein (LDL) (apoC
      III-HP), but this reduction was proportionate so that the apo-C-III-HS/apoC-III
      HP ratio, an indirect estimate of the efficiency of lipoprotein lipase (LPL), was
      unchanged. Apolipoprotein A-I concentrations also decreased significantly
      (withdrawal 140.7 +/- 27.0 vs. replacement 127.1 +/- 30.0 mg%, P < 0.01) in
      parallel with the changes in LP-A-I and LP-A-I:A-II particles (LP-A-I withdrawal
      35.8 +/- 7.7 vs. replacement 31.5 +/- 6.3; LP-A-I:AII withdrawal 104.9 +/- 20.0
      vs. replacement 95.5 +/- 26.0; P < 0.05). CONCLUSION: These findings indicate
      that thyroid hormone influences the transport not only of both TG-rich and
      cholesterol-rich apoB-containing lipoprotein particles but also of those that
      contain apoAI.

PMID- 9615902
TI  - Increased risk of death from primary hyperparathyroidism--an update.
AB  - BACKGROUND: The aim of this study was to investigate the risk of death among
      patients treated for primary hyperparathyroidism during the past decade. METHODS:
      Using the national patient register, all patients operated on for primary
      hyperparathyroidism in Sweden during 1987-94 were identified and then searched
      for in the national register of deaths and causes of death during the same
      period. The control group was the whole Swedish population, matched for age, sex
      and calendar year. RESULTS: We found that patients treated for primary
      hyperparathyroidism run an increased risk of death. The risk ratios for death
      from cardiovascular disease were 1.71 for male and 1.85 for female patients.
      These estimations are of high precision because of the large patient series (n =
      4461), with 95% confidence limits of 1.34-2.15 and 1.62-2.11 for men and women
      respectively. CONCLUSION: This finding, together with previous findings that
      parathyroid adenoma weight, serum calcium level and parathyroid hormone level are
      predictive of the risk of death, suggests the possibility that surgery in
      patients with primary hyperparathyroidism may offer not only relief from signs
      and symptoms but also improved prognosis.

PMID- 9615903
TI  - Increased incidence of cardiovascular diseases in primary hyperparathyroidism--a
      cause for more aggressive treatment?

PMID- 9615904
TI  - Relationship between insulin's haemodynamic effects and insulin-mediated glucose
      uptake.
AB  - BACKGROUND: Insulin resistance and hyperinsulinaemia are associated with
      hypertension. The relationship between insulin's metabolic and haemodynamic
      actions has not been fully elucidated however. METHODS: We investigated, using
      the euglycaemic clamp technique, the relationship between insulin-mediated
      glucose uptake and insulin-induced changes in leg blood flow and cardiac index in
      13 healthy subjects. As insulin's effects on blood flow are time dependent,
      studies were performed during a 4-h insulin (50 mU kg-1 h-1) infusion period.
      RESULTS: Mean arterial pressure during insulin infusion increased (82.9 +/- 6.7
      to 89.8 +/- 7.7 mmHg; P < 0.001), whereas heart rate was unaltered. Leg blood
      flow gradually increased from 1.09 +/- 0.57 to 1.47 +/- 0.67 mL min-1 dL-1 during
      the second hour, and to 1.65 +/- 0.68 mL min-1 dL-1 during the fourth hour of the
      clamp (P = 0.01). Stroke volume index increased from 56.5 +/- 13.3 to 63.7 +/-
      16.3 mL m-2 (P = 0.004) and cardiac index from 3.42 +/- 1.02 to 3.73 +/- 1.05 L
      min-1 m-2 (P = 0.04). The insulin-mediated glucose disposal and the increases in
      leg blood flow were not correlated during the second hour (r = 0.21, P = 0.51)
      but showed a strong correlation during the fourth hour of the clamp (r = 0.88, P
      < 0.001). Insulin-mediated glucose disposal was not correlated with the increases
      in cardiac index. CONCLUSION: Thus, insulin-mediated muscle blood flow may be an
      important contributor to glucose uptake during sustained exogenous
      hyperinsulinaemia aiming at physiological insulin levels.

PMID- 9615905
TI  - A methylenetetrahydrofolate reductase gene polymorphism in ischaemic stroke and
      in carotid artery stenosis.
AB  - METHODS: A biallelic polymorphism of the methylenetretrahydrofolate reductase
      (MTHFR) gene, reported to influence the plasma level of homocysteine (Hcy), was
      investigated for a possible role in influencing the risk of ischaemic
      cerebrovascular disease (ICVD) and occlusive atherosclerosis in 126 patients with
      ischaemic stroke and 70 patients with internal carotid artery (ICA) stenosis.
      RESULTS: Only minor differences were observed between different groups of
      patients and control subjects. Although 47% of ICA stenosis patients had
      increased plasma Hcy, the MTHFR genotype did not correlate with levels of either
      Hcy, folic acid or vitamin B12. In addition, the MTHFR genotype did not affect
      Hcy levels, even in the presence of low blood folate. CONCLUSION: We conclude
      that this common MTHFR gene polymorphism does not exert a significant influence
      on the risk of developing ICVD or ICA stenosis, and does not cause the increased
      level of Hcy observed in ICA stenosis.

PMID- 9615906
TI  - Lack of influence of apolipoprotein E4 on lipoprotein levels in the island
      population of Sardinia.
AB  - BACKGROUND: In this study, the apolipoprotein E (apoE) genotypes as well as
      plasma lipid and lipoprotein levels have been determined for the first time in
      633 healthy and unrelated inhabitants on the island of Sardinia (291 men and 342
      women, age range 6-89 years), randomly selected in the four districts of Sardinia
      among healthy people having parents and grandparents born in the same geographic
      area. This island lies in the centre of the western Mediterranean sea with a well
      recognized peculiar and preserved genetic background. The epsilon 3 allele
      frequency (0.897) is higher than that previously reported in southern and
      mainland Italy and is one of the highest in Europe and among Caucasians; epsilon
      2 allele frequency (0.040) is the lowest in Europe; epsilon 4 (0.063) is
      unusually low and, most interestingly, does not change in the different age
      groups, i.e. does not decrease in old subjects. RESULTS: Lipid and lipoprotein
      analysis confirm that total cholesterol and low-density lipoprotein (LDL)
      cholesterol levels are lower than those described in mainland Italy; moreover, in
      this large Sardinian series, accurately selected, epsilon 4 allele did not
      influence total cholesterol (P = 0.270), LDL-cholesterol (P = 0.667) and high
      density lipoprotein (HDL)-cholesterol (P = 0.549) as in other populations. In
      contrast, subjects carrying the epsilon 2 allele were found to have significantly
      lower total cholesterol (P = 0.001) and LDL-cholesterol (P = 0.001) levels than
      epsilon 3 carriers. CONCLUSION: The low epsilon 4 frequency and the lack of
      influence of this allele on lipid metabolism is a unique characteristic and, to
      date, has been described only in Sardinia among Caucasians; it might contribute
      to the low prevalence of coronary artery disease in this island.

PMID- 9615907
TI  - Cytokine autoantibodies in multiple sclerosis, aseptic meningitis and stroke.
AB  - BACKGROUND: We have recently described the induction of anti-cytokine
      autoantibodies during bacterial infections and autoimmune diseases as a mechanism
      for cytokine regulation. METHODS: Herein, we study the occurrence of
      autoantibodies to pro- and anti-inflammatory cytokines in cerebrospinal fluid and
      plasma from patients with multiple sclerosis, aseptic meningitis and stroke.
      RESULTS: Increased levels of autoantibodies to interferon gamma, tumour necrosis
      factor alpha, interleukin 4 and interleukin 10 were detected in both compartments
      of multiple sclerosis and aseptic meningitis patients. Interestingly, in
      cerebrospinal fluid from stroke patients, only autoantibodies to interleukin 4
      and interleukin 10, but not interferon alpha or tumour necrosis factor alpha were
      detected. No significant autoantibody levels were registered in plasma from
      stroke patients against all four cytokines compared with healthy control
      subjects. The latter revealed very low autoantibody levels in plasma and no
      detectable autoantibodies in cerebrospinal fluid. CONCLUSIONS: Our data show for
      the first time the occurrence of cytokine autoantibodies in these diseases, but
      their biological significance is unclear.

PMID- 9615908
TI  - Autoantibodies to cytokines.

PMID- 9615909
TI  - Association of copper to metallothionein in hepatic lysosomes of Long-Evans
      cinnamon (LEC) rats during the development of hepatitis [se e comments].
AB  - BACKGROUND: The Long-Evans cinnamon (LEC) rat has a mutation homologous to the
      human Wilson's disease gene, leading to copper-induced hepatotoxicity. The
      mechanism of how excess copper damages the liver or what chemical form of copper
      is toxic is still unclear. RESULTS: In liver cytosol, copper levels were highest
      just before the onset of hepatitis and declined thereafter. In cytosol, total
      copper was bound to metallothionein (MT). Considerable amounts of both copper and
      iron accumulated in lysosomes with increasing age and development of liver
      damage. Lysosomal levels of presumably reactive non-MT-bound copper were
      increased. In severely affected livers, large amounts of copper were associated
      with insoluble material of high density which, upon ultrastructural information,
      was found to be derived from the lysosomes of Kupffer cells. This copper-rich
      material is considered to consist of polymeric degradation products of copper-MT.
      CONCLUSION: We suggest that chronic copper toxicity in LEC rats involves the
      uptake of copper-loaded MT into lysosomes, where it is incompletely degraded and
      polymerizes to an insoluble material containing reactive copper. This copper,
      together with iron, initiates lysosomal lipid peroxidation, leading to hepatocyte
      necrosis. Subsequent to phagocytosis by Kupffer cells, the reactive copper may
      amplify liver damage either directly or through stimulation of these cells.

PMID- 9615910
TI  - The Long-Evans cinnamon (LEC) rat and copper metabolism.

PMID- 9615911
TI  - The response of smooth muscle cells to alpha-thrombin depends on its arterial
      origin: comparison among different species.
AB  - BACKGROUND: Thrombin plays a pivotal role in the pathogenesis of arterial
      thrombosis and exerts a wide spectrum of effects on the cells of vessel walls.
      METHODS: In this paper we focus on the direct role of thrombin as a mitogen for
      smooth muscle cells (SMCs) derived from different vessels from the vascular tree
      (coronary artery, aorta, carotid artery and pulmonary artery) of different
      species (human and pig). All cell populations examined responded mitogenically to
      alpha-thrombin, however the extent of this response was dependent on both
      vascular origin and the species from which vessels were derived. RESULTS:
      Thrombin (1-100 nmol L-1) induced DNA synthesis ranging from 1.5- to 4-fold
      baseline depending on cell type. Porcine coronary SMCs showed the highest
      response to thrombin (100 nmol L-1) in terms of protein and DNA synthesis (4.0 +/
      0.2-fold) and cell division (53.4 +/- 8.8%) among the tested cells. In these
      cells recombinant (r)-hirudin, a specific thrombin inhibitor, exhibited maximal
      effectiveness to block the mitogenic effect of thrombin. Human SMC response ([3H]
      thymidine incorporation) to either sera or thrombin was lower than that of
      porcine cells. In contrast, c-fos mRNA levels induced by thrombin in human SMCs
      were higher than those induced in porcine cells. In human cells, thrombin
      elicited an overexpression of c-fos and a lower rate of [3H]-thymidine
      incorporation than in porcine cells. Insulin-like growth factor I but not insulin
      showed additive mitogenic effects with thrombin in human coronary SMCs. The
      response of these cells to thrombin from different sources was a function of
      thrombin specific activity. CONCLUSION: These results suggest that the cell
      system chosen to check thrombin mitogenicity not only determines thrombin
      quantitative effects but also may affect the effectiveness of an inhibitor to
      block its biological activity.

PMID- 9615912
TI  - Effects of short-term treatment with pravastatin on the hepatic synthesis of
      cholesterol and bile acids in gallstone patients.
AB  - BACKGROUND: HMG-CoA reductase inhibitors are now the therapy of choice in the
      treatment of hypercholesterolaemia. The effects of long-term treatment with these
      substances on plasma lipoproteins, cholesterol metabolism and biliary secretion
      of lipids have been extensively studied in humans. Much less is known about the
      effects of short-term treatment. The aim of this study was to determine the time
      course of the effects of HMG-CoA reductase inhibitors on plasma lipoprotein
      levels as well as cholesterol and bile acid synthesis in gallstone patients.
      METHODS: Thirty-six patients undergoing elective cholecystectomy were included in
      the study. Except for the gallstone disease, these patients were otherwise
      healthy. Four groups of subjects were treated with the HMG-CoA reductase
      inhibitor pravastatin (Pravachol), 20 mg twice daily for 12, 24, 48 and 72 h
      preoperatively. Plasma lipoproteins and plasma levels of lathosterol and 7 alpha
      hydroxy-4-cholesten-3-one were determined before initiation of pravastatin
      treatment and on the morning of the day of the operation, lathosterol reflecting
      hepatic HMG-CoA reductase activity and 7 alpha-hydroxy-4-cholesten-3-one the
      activity of cholesterol 7 alpha-hydroxylase, the rate-determining enzyme in bile
      acid synthesis. RESULTS: All treatment groups displayed a significant decrease in
      total cholesterol and low-density lipoprotein (LDL)-cholesterol, by about 12% and
      17% respectively. Lathosterol was reduced by about 50% in all treatment groups.
      Of great interest was the finding that 7 alpha-hydroxy-4-cholesten-3-one was
      unaffected in all treatment groups. CONCLUSION: The results show that short-term
      pravastatin treatment in gallstone patients rapidly inhibits cholesterol
      synthesis and lowers plasma LDL-cholesterol levels without effects on bile acid
      synthesis.

PMID- 9615913
TI  - Antioxidant defences are reduced during the oral glucose tolerance test in normal
      and non-insulin-dependent diabetic subjects.
AB  - BACKGROUND: Free radical production has been reported to be increased in patients
      with diabetes mellitus, and it has been suggested that hyperglycaemia may
      directly contribute to the generation of oxidative stress. The aim of the present
      study was to evaluate the effects of an acute increase in glycaemia on plasma
      antioxidant defences. RESULTS: During the oral glucose tolerance test (OGTT),
      plasma concentration of protein-bound sulphydryl (SH) groups, vitamin C, vitamin
      E and uric acid significantly decreased in normal as well as non-insulin
      dependent diabetes mellitus (NIDDM) subjects. Total plasma radical-trapping
      activity, which evaluates plasma antioxidant capacity due to known and unknown
      antioxidants present in the plasma as well as their mutual co-operation, was also
      significantly reduced. CONCLUSION: This finding supports the hypothesis that
      hyperglycaemia may, even acutely, induce an oxidative stress.

PMID- 9615914
TI  - Influence of plasma phytanic acid levels in Refsum's disease on the behaviour of
      the erythrocyte membrane sodium-lithium countertransporter.
AB  - BACKGROUND: Abnormal behaviour of the erythrocyte membrane sodium-lithium
      countertransporter (SLC) is associated with plasma triglyceride concentrations.
      Refsum's disease is characterized by progressive neurological dysfunction and
      accumulation of phytanic acid, an isoprenoid fatty acid, in fat-containing
      tissues. METHODS: This study explored the effects of plasma phytanic acid on SLC
      kinetics in nine Caucasian patients with Refsum's disease and in age- and sex
      matched Caucasian control subjects. RESULTS: A dose-dependent association was
      seen between countertransporter maximal velocity and phytanic acid content of low
      density lipoprotein (LDL)-cholesterol (r = -0.61, r = -0.65 respectively; P =
      0.05, P = 0.04) and high-density lipoprotein (HDL)-cholesterol (r = -0.81, -0.82
      respectively; P = 0.005, P = 0.003). No significant association was seen with the
      sodium affinity of the transporter (r = -0.44, P = 0.20, for LDL; and -0.43, P =
      0.21, for high-density lipoprotein). CONCLUSION: These findings suggest that
      phytanic acid may alter the behaviour of the sodium-lithium countertransporter.

PMID- 9615915
TI  - Human cytokine gene nucleotide sequence alignments, 1998.

PMID- 9615916
TI  - A novel NlaIII polymorphism in the human IL-6 promoter.

PMID- 9615917
TI  - An MspA1 I polymorphism in exon 1 of the human TNF receptor type I (p55) gene.

PMID- 9615918
TI  - Identification of a rare Bg/II polymorphism in the promoter region of the human
      TNF receptor type I (p55) gene.

PMID- 9615919
TI  - Is AIDS due to the clonal senescence of CD4 lymphocytes?

PMID- 9615920
TI  - Mortality patterns suggest lack of senescence in hydra.
AB  - Senescence, a deteriorative process that increases the probability of death of an
      organism with increasing chronological age, has been found in all metazoans where
      careful studies have been carried out. There has been much controversy, however,
      about the potential immortality of hydra, a solitary freshwater member of the
      phylum Cnidaria, one of the earliest diverging metazoan groups. Researchers have
      suggested that hydra is capable of escaping aging by constantly renewing the
      tissues of its body. But no data have been published to support this assertion.
      To test for the presence or absence of aging in hydra, mortality and reproductive
      rates for three hydra cohorts have been analyzed for a period of four years. The
      results provide no evidence for aging in hydra: mortality rates have remained
      extremely low and there are no apparent signs of decline in reproductive rates.
      Hydra may have indeed escaped senescence and may be potentially immortal.

PMID- 9615921
TI  - Immunological confirmation of elevated levels of CuZn superoxide dismutase
      protein in an artificially selected long-lived strain of Drosophila melanogaster.
AB  - Oxidative stress-induced damage is a major causal factor leading to the loss of
      function characteristic of the aging process. Various antioxidant defenses are
      marshalled by the organism so as to combat this oxidative damage and delay the
      onset of senscence. CuZnSOD is one of the major antioxidant enzymes and has been
      shown to play an important role in the extended longevity of Drosophila
      melanogaster. Although assays exist with which to measure the CuZnSOD RNA
      prevalence and enzyme activity, there existed no antibodies that permitted the
      measurement of the actual amount of Drosophila enzyme protein present.
      Development of such a tool would enhance our ability to understand mechanisms of
      antioxidant gene expression in this organism. We have developed a polyclonal
      antibody against synthetic SOD peptides that is specific for Drosophila CuZnSOD
      as shown by Western blots. It is very sensitive when tested against native
      Drosophila CuZnSOD protein. Its use in our experimental system confirms the prior
      RNA and enzyme activity measurements that indicate that our genetically selected
      long-lived strain has significantly higher levels of CuZnSOD protein than does
      the appropriate control strain.

PMID- 9615922
TI  - The effect of food restriction on the composition of intestinal microflora in
      rats.
AB  - The effect of a food-restricted diet on the fecal microflora of rats was studied
      by determining total anaerobic bacteria, bacterial cellular fatty acids, and the
      predominant intestinal bacteria shown by polymerase chain reaction (PCR) primers
      specific for the 16S rRNA gene sequences of 12 bacterial species. Twenty-four
      female Fischer 344 rats, 57 days old were divided into two groups and maintained
      on an NIH-31 diet. One group was fed ad libitum while the other group received
      60% of ad libitum food intake (40% food restriction supplemented with vitamins
      and minerals equal to the ad libitum animals). After 2, 10, and 20 weeks on this
      dietary regimen, groups of four animals were sacrificed and the intestinal
      contents analyzed for changes in the bacterial flora. The anaerobic population
      for two-week (short-term) food-restricted rats was 3.2 x 10(8) per gram, slightly
      less than the 9.1 x 10(8) per gram found in the ad libitum-fed rats. The
      anaerobic populations in 20-week food restricted and ad libitum fed rats were 1.9
      x 10(9) and 2.7 x 10(9) per gram, respectively. The total anaerobic population
      did not change significantly in either group during the 20-week study. No
      statistically significant differences were observed in the bacterial cellular
      fatty acid profiles between the two groups as determined by gas-liquid
      chromatography. PCR analysis of the intestinal contents indicated no significant
      shifts in the predominant flora due to dietary changes. The results, using three
      different methods to detect changes in the rat intestinal microflora, suggest
      that long-term dietary restriction had little effect on the microflora of female
      Fischer 344 rats.

PMID- 9615923
TI  - Differential effect of aging on cholesterol modulation of carbachol-stimulated
      low-K(m) GTPase in striatal synaptosomes.
AB  - Previous research has suggested that age-related decline in physiological
      functions may be the result of substantial alterations in membrane molecular
      structure. The purpose of the present experiments was to elucidate the role of
      cholesterol domains in the age-related decline in receptor-G-protein interactions
      in striatal synaptosomes. We observed a significant age-related deficit in
      muscarinic cholinergic stimulated Low-Km GTPase activity and its age-related
      susceptibility to cholesterol treatment in range of 10(-10)-10(-5) M. Treatment
      of synaptosomes from old rats with cholesterol in range of 10(-8)-10(-6) M
      restored the Low-Km GTPase activity up to the level seen in young animals and
      reached a maximum at 10(-7) M. In synaptosomes from young rats, however,
      cholesterol treatment did not have any effect on striatal Low-Km GTPase activity.
      We observed significant alterations in the membrane lipid composition of striatal
      synaptosomes as a function of age. Our results suggested a significant
      interaction of age and cholesterol treatment on physical properties of striatal
      synaptosomes. Thus, the present results of experiments in vitro support our
      previous results of experiments in vivo and suggested an interaction of
      cholesterol domains with muscarinic-cholinergic receptor G-protein alpha subunit
      coupling/uncoupling through regulation of physical properties of striatal
      synaptosomes.

PMID- 9615924
TI  - CD28 expression in T cell aging and human longevity.
AB  - Functional decrements of the immune system have a major contribution to aging and
      age-related diseases. Here, we further characterize the decline in proportion of
      CD28-positive T cells previously identified in centenarians. Cohorts of 97
      centenarians, 40 subjects aged 70-90 (ELD group), and 40 young adults (under age
      40) were phenotyped for T cell surface expression of CD28, CD4, and CD8 antigens.
      The significant decline in T cells expressing CD28 (p < 10(-4) for comparisons
      between adults and either ELD or centenarians) affects preferentially the CD8+
      subset of T cells. This decline accounts largely for the age-related diminution
      of T cell responsiveness to mitogenic signals. CD28 expression is modulated in T
      cell cultures in a growth-related fashion and this modulation is dampened in
      cultures from centenarians. We propose that the decrease in CD28 expression
      reflects a compensatory adaptation of the immune system during aging in the face
      of chronic stimulation.

PMID- 9615925
TI  - [The biocompatibility of catheters and stents used in urology].
AB  - Biocompatibility can be interpreted as the optimal combination of a series of
      interactions occurring at the material-tissue interface as soon as these two
      systems are in contact. It is a multifactorial interface property which
      integrates all of the phenomena involved in a biological environment i.e. absence
      of toxicity of the material for the body and absence of degradation of the
      material by the body. Biocompatibility can be evaluated in a normative context by
      using in vivo techniques in animals or in vitro techniques using cell cultures
      allowing the study of cytotoxicity (related to a concept of safety) and
      cytocompatibility (related to biological acceptability) of a material. Because of
      their intimate contact with the urothelium throughout implantation, the
      biocompatibility of catheters and stents constitutes a major requirement. This
      review presents the current data reported in the literature concerning the
      evaluation of the biocompatibility of materials used in urology. The main
      problems encountered are alterations of the urothelium, such as erosions or, on
      the contrary, mucosal hyperplasia, and the existence of incrustations developing
      on these materials.

PMID- 9615926
TI  - [Patient information: advancements in jurisprudence. The example of silicone].
AB  - Medical procedures are performed in the context of a contract between the
      physician and the patient. Failure to comply with this contract may engage the
      physician's responsibility. For a long time, the physician's responsibility was
      engaged because of technical errors or, more rarely, lack of information or
      consent, which had to be proved by the patient. In the case of litigation, a
      recent decision by the Court of Appeal (25 February 1997) requires physicians to
      demonstrate that they have effectively and validly informed the patient. This
      article studies the content of this information. It suggests a method which, set
      up under the authority of scientific societies, would allow, in our discipline,
      the proposal of information forms designed to inform our patients and to preserve
      our responsibility. Finally, this approach is illustrated by the study of
      tolerability of materials containing silicone.

PMID- 9615927
TI  - [Laparoscopic surgical treatment of simple cysts of the kidney].
AB  - OBJECTIVE: To demonstrate the efficacy of laparoscopic treatment of symptomatic
      renal cysts or cysts suspicious of malignancy. MATERIAL AND METHODS: 10 patients
      (mean age: 58 years) were operated by laparoscopy either for compressive or
      symptomatic cysts (7 cases), or for cysts suspicious of malignancy (3 cases). The
      mean cyst diameter was 7.8 cm. All patients were evaluated by preoperative CT
      scan. There were 8 Bosniak type I and 3 Bosniak type II cysts. RESULTS: The
      procedure was performed via an intraperitoneal approach (8 cases) or via a
      retroperitoneal approach (2 cases). The mean operating time was 92 min and the
      mean hospital stay was 5.4 days. One patient was operated (conversion to
      lumbotomy) for uncontrolled haemorrhage of the base of the cyst. The 10 cysts
      were found to be benign histologically. All 10 patients are asymptomatic (mean
      follow-up: 8.3 months) with disappearance of the cyst on the follow-up CT scan.
      CONCLUSION: Laparoscopic treatment of renal cysts is feasible and effective.
      However, this treatment must be reserved for Bosniak type I and II cysts,
      associated with a low risk of malignancy.

PMID- 9615928
TI  - [Fragmentation of ureteral calculi using a holmium YAG laser].
AB  - PURPOSE: Evaluation of the Holmium YAG laser wave length in the treatment of
      ureteric calculi. MATERIAL AND METHODS: 84 ureteric stones in 62 patients were
      subjected to lithotripsy by the Ho-YAG laser (wave length 2100 nm). Of the stones
      treated 54 were lower ureteric, 21 were middle ureteric and 9 were upper
      uireteric stones. Thirty five stones were subjected to previous unsuccessful
      endoscopic lithotripsy procedures or ESWL. The mean diameter of the stones was
      1.6 cm. The energy parameters followed in the study were 1.5 joules with
      frequency of 15 to 20 pulse/sec (22-30 watts). KUB was carried out one week and
      one month after the procedure and intravenous urography was performed 2 months
      later to evaluate upper tract improvement and to detect any stricture formation
      alone the ureter. RESULTS: Of the 84 stones, 75 (89.2%) were successfully
      fragmented: 52 (96%) of the lower, 17 (80.9%) of the middle and 6 (66.6%) of the
      upper ureteric stones. The cause of failure in fragmentation of the remaining 9
      stones (10.7%) was due to failure of instrumentation nor machine malfunction that
      aborted the procedure. The average operative time per case was approximately 30
      minutes and the lasing time was approximately 7 minutes. No major complications
      related to the laser treatment were encountered except in one patient who needed
      prolonged internal ureteral stenting. CONCLUSION: Ho-YAG laser lithotripsy is
      useful and very effective in the endoscopic treatment of ureteric stones. It is
      safe, if carefully applied and most of the cases can be carried out as an
      outpatient procedure.

PMID- 9615929
TI  - [Results of BCG in the treatment of pTa and pT1 bladder tumors. Evaluation of a
      long protocol using 75 mg of Pasteur strain BCG].
AB  - OBJECTIVES: Evaluation of a protocol of intravesical BCG therapy using 75 mg of
      Pasteur strain BCG with 2 years of maintenance treatment, and a follow-up of up
      to 60 months. MATERIAL AND METHODS: 189 patients treated by transurethral
      resection (TUR) for a pTa (N = 80) or pT1 (N = 109) bladder tumour were included
      in the study. The local and general safety was excellent. We retrospectively
      compared this series to a group of patients treated by TUR alone (N = 42) another
      group treated with TUR and Mitomycin C (MMC) (N = 81). The 3 groups were
      statistically comparable. RESULTS: At 48 months, 62% of patients treated with BCG
      were recurrence-free, versus only 18% for patients treated with TUR alone and 38%
      for patients treated with TUR and MMC (p = 0.001). At 42 months, 11% of pT1
      tumours treated with BCG had progressed to invasive carcinoma, and this
      progression occurred during the first 18 months in every case. In comparison,
      this progression was observed in 25% of pT1 tumours treated by TUR alone and 21%
      of tumours treated with TUR and MMC. CONCLUSIONS: Our study confirms the efficacy
      of our BCG protocol ro reduce the potential for recurrence and progression of
      superficial bladder tumours, despite reduction of the dose to 75 mg. It also
      suggests the superiority of BCG compared to MMC in terms of recurrence and
      progression.

PMID- 9615930
TI  - [Use of the Valtrac ring for digestive anastomoses in urology: apropos of 16
      cases].
AB  - The Valtrac ring is a biofragmentable ring used for gastrointestinal anastomoses.
      Over a two-year period, 15 anastomoses in 16 patients (mean age: 60 years) were
      performed with the Valtrac ring: 10 ileal, 4 ileocolonic, and 1 jejunojejunal
      anastomoses. One anastomosis could not be performed because of an excessively
      narrow ileal lumen. The mean stay in the intensive care unit was 3 days: gastric
      aspiration was maintained for an average of 1 week, as return of gastrointestinal
      motility was long, with first flatus on the 6th day and the first stools on the
      7th day. Complications consisted of 2 cases of gastrointestinal fistula (11th and
      13th days) one of which was fatal, evisceration on the 7th day, a transient
      partial bowel obstruction and one bowel obstruction treated medically on the 27th
      day, due to pancreatitis. Our results are not identical to those reported in the
      literature. It is often difficult to insert the current form of the Valtrac ring
      into a healthy ileum, as the smallest ring is often too large. In contrast with
      gastrointestinal surgery, the anastomoses performed in urology involve a non
      thickened, non-distended small intestine.

PMID- 9615931
TI  - [The value of prostatic biopsy in tumor mapping].
AB  - OBJECTIVES: Prostatic biopsies, a diagnostic tool, are also used as prognostic
      elements before radical prostatectomy. Their sites within the prostatic gland
      constitute one of these prognostic criteria. The authors compared the site of
      positive prostatic biopsies with that of the tumour after radical prostatectomy
      in order to study the value of this prognostic factor and the way in which it can
      be improved. MATERIAL AND METHODS: From 1988 to 1996, 166 localized prostatic
      tumours treated by radical prostatectomy were diagnosed by 6 systematized
      ultrasound-guided transrectal biopsies and 3 supplementary median biopsies
      performed from the base to the prostatic apex. The site of positive biopsies was
      compared to that of the tumour within the prostatic gland. RESULTS: Of the 996
      sextant biopsies performed, 331 (33%) were positive, i.e. 1.99 biopsies per
      prostate. 92 (19%) median biopsies were positive. 331 positive sextant biopsies
      corresponded to a tumour within the prostate with a specificity of 81.5%, a
      sensitivity of 39.4%, a positive predictive value (PPV) of 83.3%, a negative
      predictive value (NPV) of 36.4% and an accuracy of 52%. For 3 median biopsies,
      the sensitivity was 70.3%, the specificity was 91.6%, the PPV was 61.9%, the NPV
      was 94%, and the accuracy was 82%. The weight of the prostate (prostates less
      than and greater than 45 g), influenced these results, as PPV decreased from
      90.8% to 76.1% while NPV increased from 32.9% to 37.8%. CONCLUSION: Negative
      biopsies in a prostatic zone after 6 randomized biopsies do not exclude the
      presence of tumour in this zone and cannot be used as a prognostic element before
      radical prostatectomy for the therapeutic management. The presence of negative
      biopsies in a prostatic zone must be interpreted by taking the prostatic weight
      into account. 3 median biopsies are more accurate and less influenced by
      prostatic weight.

PMID- 9615932
TI  - [The use of MRI with a pelvic phased array antenna in the evaluation of the gland
      and tumor volume of clinically localized prostatic adenocarcinoma].
AB  - Prostate cancer is clinically understaged in 50% of cases. It was improved with
      the use of random biopsies, PSA analysis (balanced and unbalanced) and Gleason
      grade on biopsies. Traditional imaging techniques such as endorectal
      ultrasonography and CT Scan are known to be of no interest. MRI is a non-evasive
      technique which allows the three dimensional study of an organ with a high
      quality of tissue contrast. Moreover, the positioning of surface antennae or
      "phased array" allowed improvement in spatial resolution. OBJECTIVE: To determine
      whether MRI allows an accurate staging of clinically localised adenocarcinoma by
      the direct estimation of capsular effraction, measure of glandular and tumor
      volumes and finally by obtaining reliable PSAd. MATERIAL AND METHODS: A
      prospective study was done from March 1995 to November 1996 on 55 patients with a
      clinically localised adenocarcinoma. MRI 1 Tesla Imager (SIEMENS), pelvic phased
      array antennae. FSE sequences (T1 and T2), axial and frontal. Evaluation of
      volumes by on-screen. Standford protocol for histo-pathologic reading on the
      axial cuts. Direct planimetry on a millimetre paper. RESULTS: Reliable estimation
      of glandular volume (average difference 0.7 cc). Sub-evaluation of tumoral volume
      (average difference 1.04 cc) with a 30% margin of error, accuracy 87%. Tumoral
      stage exact in almost 90% of the cases with a PPV of 94%. CONCLUSION: Prostatic
      MRI, using surface antennae, allows to complete the conventional stage by stage
      development by correctly diagnosing 75% of locally evolved stages. Its limits are
      linked to the nature of the signal of the tumorous tissue as to the localisation
      of neoplasic lesions.

PMID- 9615933
TI  - [Complete perineal prostatectomy carries an increased risk of capsular incision
      in healthy and cancerous tissue].
AB  - OBJECTIVES: To compare positive resection margin rates in tumour tissue and
      healthy tissue according to whether total prostatectomy for cancer is performed
      via a retropubic or transperineal approach. PATIENTS AND METHODS: This
      retrospective, non-randomized study was based on 94 patients suffering from
      clinically localized cancer (T1-T2) of the prostate operated either via a
      retropubic (46: group 1) or perineal (48: group II) approach. All slides were
      reviewed by two pathologists not informed about the clinical course. The
      frequency of tumour margins associated with extracapsular invasion, capsular
      incision, without extracapsular extension of the tumour, and finally the
      incidence of capsular incisions exposing tumour tissue, were determined. RESULTS:
      While the number of positive resection margins was equivalent in the two groups
      (61% for group I versus 56% for group II), it was higher in the perineal group
      (43% versus 29%, p < 0.05) when the tumour was confined to the gland (pT2). A
      higher incidence of resection margins in healthy tissue was also observed in
      group II (90% versus 37%). CONCLUSION: Transperitoneal prostatectomy is
      associated with a higher incidence of resection margins in tumour tissue in
      patients with prostate-confined cancer. Analysis of the resection margins in
      healthy tissue suggests that the surgical incision is a predisposing factor to
      their creation.

PMID- 9615934
TI  - [Epididymal manifestations of urogenital tuberculosis].
AB  - OBJECTIVE: To define the epidemiological, anatomical, clinical and therapeutic
      aspects of tuberculous epididymitis in adults in the tropics. MATERIAL AND
      METHODS: This was a retrospective study of 11 cases of confirmed and treated
      tuberculous epididymitis. RESULTS: The most frequently affected age-group was 40
      49 years. The commonest expression was that of a chronic epididymal nodule. The
      diagnosis was confirmed by histological examination of the epididymectomy
      specimen (10 cases) and bacteriology in one case. Combination antituberculous
      chemotherapy was systematically administered and epididymectomy was performed in
      all patients. CONCLUSION: The diagnosis of tuberculous epididymitis is often very
      difficult in the absence of a history of recent or active tuberculosis. However,
      this diagnosis must be considered in any case of chronic epididymal nodule,
      particularly in a context of infertility. The very mutilating treatment consists
      of epididymectomy in chronic forms, which also constitutes a diagnostic
      confirmation procedure, hence the value of prevention based on eradication of
      tuberculosis.

PMID- 9615935
TI  - [Spermatic cord torsion in children].
AB  - OBJECTIVES: Definition of prognostic factors for torsion of the testis in
      children. MATERIAL AND METHODS: From January 1986 to December 1996, 91 children
      were operated for torsion of the testis. Torsions were observed at all ages of
      childhood, but with two frequency peaks: during the neonatal period and in
      adolescence. Typical clinical features were observed in only three-quarters of
      cases. RESULTS: Thirty-nine testes were considered to be necrotic versus 52 with
      a chance of recovery. Factors of poor prognosis were: neonatal forms, delayed
      management or tight torsion with several turns. 28 of the necrotic testes were
      conserved: two were complicated by purulent necrosis, but 14% retained normal
      trophicity on long-term examination. CONCLUSION: The possibility of torsion at
      all ages of childhood and the frequently incomplete clinical features means that
      emergency surgical exploration must always be performed in the case of testicular
      pain. A conservative attitude is motivated by the possibility of recovery of
      testes considered to be necrotic at operation.

PMID- 9615936
TI  - [Carcinoma of Bellini's collecting tubules. Apropos of a case].
AB  - Carcinoma of the papillary ducts of Bellini is a rare malignant tumour of the
      kidney, with a generally unfavourable prognosis because of late diagnosis, often
      at the state of metastases. The diagnosis is based on pathological examination of
      the nephrectomy specimen with immunohistochemical study. The role of adjuvant
      chemotherapy needs to be evaluated.

PMID- 9615937
TI  - [Benign ureteral polyps in children: apropos of a case].
AB  - Ureteric polyp is a benign lesion, and an uncommon cause of hydronephrosis in
      children. It is associated with intermittent lumbar pain and haematuria. The
      diagnosis is usually based on intravenous urography or retrograde urography.
      Treatment must be conservative and consists of simple resection of the polyp,
      associated with varying degrees of ureteric resection depending on the size of
      the lesion. No case of recurrence after treatment has been reported to date. The
      authors report a case in a 7-year-old boy and present a review of the literature.

PMID- 9615938
TI  - [Treatment using percutaneous arterial embolization of post-traumatic priapism in
      children].
AB  - High flow rate priapism was diagnosed in a 14-year-old adolescent 5 days after a
      fall onto the perineum. Highly selective embolization of the 2 internal pudendal
      arteries was performed with gelatin (SPONGEL). Rapid resolution of the priapism
      as well as return of normal erection were observed within 48 hours. Doppler
      ultrasound revealed a high flow rate and identified the side of the traumatized
      artery. Endovascular embolization allows effective treatment of traumatic
      arteriocavernous fistula.

PMID- 9615939
TI  - [Inverted Y partial ureteral duplication. Apropos of an unusual case].
AB  - Inverted Y partial ureteric duplication corresponds to the presence of a variable
      length of duplicated ureter before entering the bladder in an orthotopic or
      ectopic position. A case od inverted Y partial ureteric duplication with ureteric
      confluence in the hilum of the kidney associated with anastomosis of an ectopic
      ureter in the epididymis is reported. The description of this original case is
      compared with the data of the literature.

PMID- 9615940
TI  - [Acquired scrotal hyperplasia: an unesthetic and functionally troublesome
      condition].
AB  - The authors report a case of acquired scrotal hyperplasia and describe it
      surgical management. The result at four months was satisfactory.
      Pathophysiological hypotheses and psychological implications are discussed.

PMID- 9615941
TI  - [Intravesical instillation in the treatment of superficial tumors of the
      bladder].
AB  - Bladder instillations represent the most significant progress in the management
      of superficial bladder cancer over the past twenty years. Intravesical
      chemotherapy significantly alters the rate of recurrence. Intravesical BCG
      reduces significantly the risk of recurrence and progression. Side effects are
      common and in the case of BCG severe but rare complications may be encountered
      during intravesical instillations. Therefore proper use, prevention of
      complication and careful follow up for tolerance and efficacy of bladder
      instillations are mandatory. They represent for high risk superficial bladder
      cancer a therapeutic test. An early failure for these tumors means a potential
      aggressiveness requiring radical therapy. These various aspects are developed
      from a practical point of view.

PMID- 9615942
TI  - [A new treatment procedure for stress urinary incontinence: sub-urethral support
      using a Prolene sling under local anesthesia].
AB  - An original technique for the treatment of USI under local anaesthesia is
      described. It consists of insertion of a Prolene sling under the middle part of
      the urethra. This sling is not placed under tension, but simply supports the
      suburethral region. In a series of 22 patients without prolapse requiring
      surgical correction and presenting USI confirmed by clinical examination, 20 were
      totally cured by this technique and the postoperative voiding flow rate was not
      decreased. This technique therefore appears to be simple, non-dysuric and
      effective.

PMID- 9615943
TI  - [Smoking behavior of pregnant patients and mothers with young children].
AB  - The aim of the study is to analyse the smoking behaviour of pregnant women and
      mothers with young children and to identify sociodemographic factors for the
      nicotine consumption of these persons. Data basis are the national and regional
      health examination surveys of the German Cardiovascular Prevention Study (GCP).
      Included were 8385 females in the age group 25-40 years. 326 (3.9%) of these
      females were pregnant at the time of the survey, and 2538 (30.3%) were mothers
      with one or more children, aged up to 5 years. Smoking behaviour, family status,
      number and age of the children and other sociodemographic variables were
      determined with a self-administered standardised questionnaire. Altogether, 39.4%
      of the 8385 females reported that they were current smokers. The prevalence of
      smoking for females without young children was slightly higher (42.3%). 20.6% of
      all pregnant females were current smokers. For mothers in the lowest social
      class, the smoking prevalence was two times higher compared to mothers in the
      highest social class. Unmarried and divorced mothers yielded a very high smoking
      prevalence. These results suggest that there is a need for prevention and health
      promotion programs for pregnant females and young mothers. Special emphasis
      should be targetted at unmarried young mothers and mothers from socially
      disadvantaged population groups.

PMID- 9615944
TI  - [Nutritional balance of breakfast of children 7 to 11 years of age: comparison
      between school health education and eating behavior at home].
AB  - Following the favourable impact of a health education programme carried out in a
      school setting concerning "healthy eating at breakfast", the consumption of food
      at home for all meals, and separately at breakfast time was evaluated by using a
      "food-frequency" questionnaire. These results were then compared with the results
      of the school health education programme which focused primarily on breakfasts.
      The results of the survey, which included 80 children between 7 and 11 years old,
      show a great stability in the choice of foods, and during the action interesting
      variations concerning the respective proportions of nutriments according the
      recommended dietary allowances. We noticed an increase in the consumption of
      glucides, starch, vegetable proteins, and certain micronutriments. These changes
      are minor, but they may have a great importance if they spread to the whole
      nutrition. One can advise to generalise such school health education
      interventions.

PMID- 9615945
TI  - Teaching physicians about different measures of risk reduction may alter their
      treatment preference.
AB  - We explored during a postgraduate workshop whether basic teaching about absolute
      and relative effect measures changed physicians' perceptions of the benefit to be
      derived from modifying particular cardiovascular risk factors. Before and after
      instruction physicians were asked about the priority they would give to
      interventions to reduce four risk factors of coronary heart disease in two male
      patients, aged 35 and 65 years with multiple risk factors. They were given
      information about the relative risk (RR), absolute risk reduction (ARR) and the
      number of patients who need to be treated (NNT) to prevent one event associated
      with the modification of each risk factor. Ratings of 48 of the 67 participating
      physicians (71.6%) were evaluated. About half did not change their choices
      regarding the benefit from a particular intervention. Among those who changed,
      the new choice was in favor of the patient with the higher ARR for three risk
      factors (hypertension, p = 0.01; smoking, p = 0.002; non-insulin-dependent
      diabetes, p = 0.05) but not the fourth (left ventricular hypertrophy, p = 0.82).
      Teaching basic principles of clinical epidemiology to physicians can have an
      impact on their perception of treatment effects. However, this will not suffice
      in itself to guarantee that this new knowledge will become part of their clinical
      practice.

PMID- 9615946
TI  - Family practitioners' remuneration and patterns of care--does social class
      matter?
AB  - The objective of the study is to examine whether medical care patterns and/or
      outcomes for patients under a prepaid system differ from those under fee-for
      service according to social class. An effect of this kind was suggested by the
      investigators reporting on the RAND Health Insurance Experiment (RAND HIE). We
      performed a cross-sectional study in family practice in Germany (fee-for-service)
      and the UK (predominantly capitation i.e. prospective payment). 778 attending
      patients aged 18 and above were included. Indicators of care, relating mainly to
      cardiovascular prevention, were collected by patient interview and questionnaire,
      doctor's questionnaire, analysis of records, and blood pressure (BP) measurement.
      Multiple linear and logistic regression models with these indicators as dependent
      variables were calculated to examine possible interactions between social class
      and system of payment. Social class as a main effect was related to diastolic BP,
      BP measurement frequency, and the number of non-pharmacological interventions to
      lower BP. The data on the process and the outcome of primary care from British
      and German family practice do not show any significant interaction between system
      of family practitioners' remuneration and patients' social class. We were unable
      to reproduce the effect postulated by the RAND HIE investigators.

PMID- 9615947
TI  - [Disparities in hospital mortality after proximal femoral fractures in East
      Germany 1989].
AB  - The revised and pseudonymized data set of the hospital discharge diagnoses of
      East Germany (German Democratic Republic, GDR) for 1989 was analyzed regarding
      the in-hospital case fatality of closed hip fractures (ICD-9 820.0, 820.2,
      820.8). The case fatality of 20.2% during an average hospital stay of 60 days
      including between-ward and between-hospital transfers is high when compared to
      international data and data for West Germany. Apart from the expected influence
      of age, fatality was reduced for cervical (intracapsular) fractures, female sex,
      and for a location of the treating hospital within East Berlin. This reduction of
      the case fatality within East Berlin by nearly two thirds after adjustment for
      age, sex, and type of fracture compared to other regions is most likely explained
      by better medical treatment facitilities within East Berlin, the former capital
      of the GDR. The regional disparities that were observed during our model analysis
      give a hint towards the influence that medical care can have on the fatality
      associated with this on a population level relevant disease.

PMID- 9615948
TI  - [Alcohol abuse and dependence in former East Germany and new united Germany].
AB  - The objective of this paper is the description of the transformation process
      after the reunification of East- and West-Germany taking the health care
      structures for alcoholics as an example. First the epidemiology of alcohol abuse
      and alcohol dependence are presented such as the individual alcohol consumption.
      These data are completed by hospital data. The social and organizational problems
      created by the transformation process after the reunification of Germany are
      described. Necessary structural changes and the expected development are
      discussed.

PMID- 9615949
TI  - [National reference centers for surveillance of infectious diseases in
      Switzerland: results of a delphi study].
AB  - The national reference laboratories are one of the tools used by public health
      authorities to control infectious diseases. The Swiss Confederation supports 9
      national reference centers (NC), each dealing with a limited number of infectious
      agents. The purpose of this study was to evaluate if this network meets present
      day needs, whether it has to be redefined, and how it can be improved. Using the
      Delphi technique, 34 experts in the field of infectious diseases were questioned
      to establish a concept for NC in Switzerland. The main result of this study is
      that official reference laboratories are considered necessary. However, depending
      on the type of infectious agent, the following types of laboratories should be
      used: national reference centers, specialized laboratories and laboratories
      abroad. The study also defined criteria for the designation of NC, their field of
      action (general objectives, tasks, duration of the mandate, infectious agent to
      be monitored), evaluation criteria, and the type of funding. Furthermore,
      possible improvements in the present system were identified and the establishment
      of good collaborations with reference centers abroad was proposed.

PMID- 9615950
TI  - Comparative efficacy of anticoccidials under the conditions of commercial broiler
      production and in battery trials.
AB  - Coccidia were isolated from a commercial broiler farm with a history of suspected
      drug resistance. The sensitivity profiles of the Eimeria spp. isolates against
      the anticoccidial drugs nicarbazin (NIC), narasin (NAR), halofuginone (HAL),
      salinomycin (SAL), meticlorpindol plus methylbenzoquate (MET), and monensin (MON)
      at the recommended dose levels were followed in three battery trials (B1, B2, B3)
      corresponding to a field study over three periods of commercial broiler keeping
      (F1, F2, F3). Shuttle programs were performed in F1 (NIC/MON) and in F2 (MET/MON)
      while only SAL was used in F3. Eimeria acervulina and E. tenella were isolated
      from indicator birds in F1 while only E. acervulina could be found during F2 and
      F3. In trial B1 the isolate from F1 was identified as resistant against HAL and
      partly resistant against NIC and MON, the two drugs that were used in F1.
      Following the replacement of NIC in the starter feed by MET the respective
      isolate from F2 showed no resistance against ionophores (trial B2) while partial
      resistance against HAL was still present. Since SAL was the most efficient drug
      in B1 and B2 only this drug was applied in F3. Apart from a resistance against
      HAL no resistance against any of the other tested anticoccidials was found in the
      isolate from F3. SAL controlled coccidiosis efficiently in the field and best
      productivity was recorded in F3. This study shows that battery trials have a good
      predictive value in respect to the efficacy of anticoccidials under the
      conditions of commercial broiler production.

PMID- 9615951
TI  - The immunology of canine leishmaniosis: strong evidence for a developing disease
      spectrum from asymptomatic dogs.
AB  - Asymptomatic mixed breed dogs (49) from a region of high incidence of visceral
      leishmaniosis in Portugal were examined for the presence of Leishmania-specific
      cellular immunity using a proliferation assay and humoral immunity using an
      indirect antibody fluorescent test (IFAT) and an ELISA. The results were compared
      directly with 25 mixed breed dogs permanently residing in a non-endemic region
      (Scotland). Unlike similar studies in humans from non-endemic areas, there was no
      evidence of any immunological response against leishmanial antigen whatsoever
      from the latter group of animals. Of the 49 dogs from Portugal, however, 20 had
      demonstrable parasite-specific cellular immunity. Depending on the assay and
      criteria used to measure a positive humoral response, 11, 16 or 24 dogs had a
      Leishmania-specific humoral response with the ELISA being the most sensitive
      assay system. While 16, 12 or 8 of the dogs had clearly only a cellular response
      (depending on which criterion was used to constitute a true antibody response)
      and 7, 8 or 12 had only humoral response, other 4, 8 or 12 of the dogs had both
      cellular and humoral responses. This study clearly demonstrates that the
      infection rate of canine leishmaniosis is not only higher than previously thought
      using serological tests alone but that the response to infection is already
      highly polarised in many asymptomatic dogs. It is postulated that an individual
      dog's position within the immunological spectrum is likely to indicate how the
      disease will progress.

PMID- 9615952
TI  - Infectivity of Cryptosporidium muris isolated from cattle.
AB  - The infectivity of a bovine isolate of Cryptosporidium muris for various animals
      was studied by transmission experiments. Neonatal BALB/c mice, adult BALB/c mice,
      SCID mice, common voles (Microtus arvalis), bank voles (Clethrionomys glareolus),
      common field mice (Apodemus sylvaticus), Mongolian gerbils (Meriones
      unguiculatus), desert gerbils (Gerbilus gerbilus), guinea pigs, rats, rabbits and
      goats were used to test the infectivity of this isolate. Among these host
      species, only Mongolian gerbils were susceptible to the infection and discharged
      C. muris oocysts in their faeces. The prepatent period for 8-week-old Mongolian
      gerbils was 15-19 days, the patent period varied between 18 and 36 days. More
      protracted chronic infections have been observed in gerbils immunosuppressed with
      methylprednisolone. No signs of clinical illness or macroscopic changes were seen
      in infected gerbils. Cryptosporidial developmental stages were detected in the
      stomach, histopathological changes were characterized by epithelial hyperplasia
      and mucosal hypertrophy without inflammatory exudate. In spite of the fact that
      C. muris was able to infect gerbils, we do not consider gerbils to be a true
      hosts for C. muris of cattle origin. Based on our results, we suggest that
      significant differences in host specificity of individual C. muris isolates
      exist, and that wild rodents are not reservoir for C. muris infection of cattle.

PMID- 9615953
TI  - Studies with recombinant proteins of Ehrlichia risticii: identification of strain
      specific antigen as a protective antigen.
AB  - Ehrlichia risticii is the causative agent of Potomac horse fever, an acute
      infectious disease of equines. To study the role of major antigens of E. risticii
      in protective immune response, we have expressed the genes of the 55 kDa, 51 kDa
      and 85/50 kDa-strain-specific antigens of the 90-12 (85 kDa antigen) and 25-D (50
      kDa antigen) strains in Escherichia coli using pRSET A, B, C system (Invitrogen,
      San Diego, CA). Mice immunized with these purified recombinant proteins of E.
      risticii developed strong and specific humoral immune response. The recombinant
      85 kDa antigen of the 90-12 strain protected mice against challenge infection
      with both E. risticii strains, whereas its homologue from the 25-D strain, the
      recombinant 50 kDa antigen, protected mice against only the homologous strain
      challenge, but not against the heterologous 90-12 strain. Sera from mice
      immunized with the 85- or 50-kDa antigens did not inhibit the replication of cell
      free Ehrlichiae in in vitro neutralization assays. Sera from normal mice and mice
      immunized with other antigens caused non-specific neutralization of E. risticii.
      Immunoglobulin G from mice immunized with the 51 kDa protein of the 90-12 strain
      caused partial in vitro neutralization of both strains of E. risticii. These
      studies demonstrate that the 85/50-kDa-strain-specific antigen of E. risticii is
      involved in immunoprotection against PHF.

PMID- 9615954
TI  - Evaluation of the prevalence of sarcoptic mange in slaughtered fattening pigs in
      southeastern Spain.
AB  - In this study the prevalence of sarcoptic mange in fattening pigs in Murcia,
      southeastern Spain was investigated. Results showed that 37% of the 1318
      slaughtered pigs examined were positive for Sarcoptes scabiei var. suis. Skin
      lesions potentially attributable to this mite were present in 92.80% of animals,
      but the parasite could be detected in only 38.60% of them. The condition of the
      ear (clean/dirty) was not a defining characteristic for the diagnosis of this
      swine disease. A sucrose flotation-concentration technique was more effective
      than direct microscopy in finding the mite in ear scrapings.

PMID- 9615955
TI  - The incidence of sheep strike by Lucilia sericata on sheep farms in Britain: a
      simulation model.
AB  - Using a combination of a temperature-dependent simulation of the population
      dynamics of Lucilia sericata and a logistic model of sheep susceptibility, based
      on patterns of faecal soiling, fleece length and fleece humidity, a deterministic
      simulation model has been constructed to predict the incidence of sheep strike by
      L. sericata on lambs and ewes in Britain. Strikes are assigned to individual
      sheep in the flock according to a negative binomial distribution. The model shows
      that the majority of the first strikes of the season occur equally on ewes and
      lambs, when ewe fleeces are long and before lamb susceptibility increases though
      faecal soiling. With each subsequent generation of gravid blowflies, however, a
      greater proportion of strikes occur on lambs, while the number of strikes
      observed on ewes remains relatively consistent throughout the season. The
      increase in strike of lambs is due to the seasonal increase in lamb faecal
      soiling, associated with rising helminth infections and lamb fleece growth. The
      model shows that at the beginning of the season the incidence of strike is
      limited by the low number of flies present: towards the end of seasons, however,
      the blowfly population had grown large enough for the number of strikes to be
      limited by the number of susceptible ewes and lambs. The model shows that the
      seasonal incidence of strike is highly sensitive to the interactions between
      temperature, rainfall and would length. Strike was most prevalent under warm, wet
      conditions. However, there is a critical period during spring, where the short
      fleeces of lambs and ewes, in the latter case due to shearing, results in the
      desiccation of egg batches. If this coincides with dry conditions, the high
      levels of mortality result in suppression of the fly population and a reduction
      in the subsequent incidence of strike.

PMID- 9615956
TI  - Efficacy of dicyclanil in the prevention of screwworm infestation (Cochliomyia
      hominivorax) in cattle castration wounds.
AB  - A field trial was carried out during summer 1996 in a commercial beef cattle farm
      located in the central area of Argentina (30 degrees 16'S, 60 degrees 30'W) to
      evaluate the efficacy of a new insect growth regulator material (dicyclanil) in
      the prevention of myiosis caused by screwworm (Cochliomyia hominivorax) larvae.
      Forty bull calves (Bos indicus x Bos taurus), 5 to 6 months old were allocated by
      ranked paris to a control (G.1) and a treated group (G.2) of the same number of
      animals. On day 0, all experimental animals were surgically castrated and calves
      of group 2 were treated topically with 20 ml as a single dose of a ready-to-use
      formulation containing 5% w/v dicyclanil. Inspections for screwworm larva
      infestation were carried out on days 4, 8, 12, 16, 19, 23 and 25 after
      castration. The incidence of egg masses on the scrotal wounds evidenced a similar
      challenge for all groups (P > 0.05 chi(2)). However, 16 animals of G.1 (80%) and
      only one of G.2 (5%) developed active myiosis, respectively. This difference was
      significant (P=0.003 X(2)).

PMID- 9615957
TI  - The prevalence of nasal mite (Pneumonyssoides caninum) infection in Norwegian
      dogs.
AB  - In a prospective study, the skulls of 250 dogs submitted for necropsy during 1993
      at the Norwegian College of Veterinary Medicine were examined for the presence of
      parasites. All skulls were cleaved sagitally, and the frontal sinuses and nasal
      cavities were visually inspected. Eighteen dogs (7%) had Pneumonyssoides caninum
      infection at necropsy. No other parasites were observed. Sixteen dogs had heavy
      or moderate infection scores and 60% of these had concurrent sinusitis. The
      infected dogs belonged to 14 different breeds, 10 were male and eight were female
      and they varied in age from four months to 10 years old. Breed distribution, sex
      and age of the infected dogs did not differ significantly from the total study
      population. This study indicates that nasal mite infection occurs commonly in
      Norwegian dogs.

PMID- 9615958
TI  - [Logotherapy. Victor Frankl 1905-1997].

PMID- 9615959
TI  - [Speech disorders in Parkinson patients].
AB  - Parkinson's disease is not only a disorder affecting locomotion, but often also
      causes speech problems. Functional impairment of articulation, phonation, prosody
      and also respiration may occur. Speech disorder is frequent in Parkinson's
      disease and often has an impact on the quality of life. Speech therapy is by no
      means offered as a matter of course to these patients. This article outlines the
      different approaches of speech therapy regarding respiration, loudness,
      articulation, prosody, and intonation. Speech therapy seems to be useful in
      patients with Parkinson's disease only if there is no cognitive impairment;
      success also depends on motivation and eventual frequent repetition of therapy
      series.

PMID- 9615960
TI  - Chronic gastrointestinal symptoms in hemodialysis patients.
AB  - INTRODUCTION: Gastrointestinal disorders occur frequently in dialysis patients.
      Few data are available on the prevalence of symptoms originating from the
      gastrointestinal tract in this group of patients. Our aim was to obtain data on
      the prevalence of chronic gastrointestinal symptoms in patients undergoing
      hemodialysis. METHODS: All 109 patients of our dialysis unit were given a
      questionnaire to complete which was previously validated and designed to measure
      the occurrence of gastrointestinal, and some general symptoms during the
      preceding year. 105 subjects responded (96% response rate). RESULTS: 79% of
      dialysis patients had at least one of the following chronic gastrointestinal
      symptoms: Esophageal symptoms were reported in 21% abdominal pain in 28% and
      dyspeptic symptoms in 48%. The irritable bowel syndrome was diagnosed in 12
      patients (11%), 40% had chronic constipation and 24% had chronic diarrhoea.
      Colonic pain was described in 20% of patients. Frequent general symptoms (such as
      weakness, headaches, insomnia and fatigue) were described in up to 51%, and
      patients were severely bothered by symptoms in up to 33% of cases. CONCLUSION:
      Although patients on hemodialysis generally report a good quality of life, the
      prevalence of gastrointestinal symptoms and of general symptoms is high and many
      dialysis patients consider these symptoms to cause major impairment of daily
      life.

PMID- 9615961
TI  - [Effects of limited mouth opening capacity (trismus) on lung function].
AB  - In the present study pulmonary function test data were obtained from 15 healthy
      volunteers and 15 patients with slightly impaired ventilation during both normal
      and maximally reduced opening of the mouth (trismus, intercuspid position). The
      aim of the study was to examine the effects of complete trismus on pulmonary
      function using objective and subjective parameters. In maximally reduced mouth
      opening, both groups showed an impairment of all subjective and objective
      pulmonary function test data. In healthy volunteers, the significant changes in
      the test data (p < 0.05) simulated mild to moderate pulmonary impairment, whereas
      patients with an already impaired pulmonary function showed a marked
      deterioration of their initial respiratory condition. The results of the
      subjective and objective parameters examined indicate that an intercuspid
      position (trismus) further aggravates pulmonary functional impairments. Complete
      trismus can be considered a risk factor to pulmonary function in patients using
      mouth-breathing as primary or supportive mode of respiration.

PMID- 9615962
TI  - Color discrimination in patients with keratoconjunctivitis sicca before and after
      artificial tear application.
AB  - BACKGROUND: The precorneal tear film is of decisive importance for the optical
      quality of the cornea. Poor stability of this film causes not only dry eye
      symptoms, but also has negative effects on optical functions of the eye, as
      previous studies on visual acuity, field test performance and contrast
      sensitivity have shown. METHODS: 60 patients with dry eyes randomized into 2
      groups of 30 underwent color vision testing with the Lanthony Desaturated 15 Hue
      test before and after instillation of artificial tear (test group) or
      physiological saline (control group) drops. RESULTS: The improvement in color
      discrimination in the group given artificial tear treatment was found to be
      slightly better than in the saline group but in both groups this improvement was
      not of statistical significance. CONCLUSION: Even though an unstable tear film
      adversely affects the optics of the eye and even mildly degraded optics can
      affect spatial visual tasks, color discrimination performance on tasks such as
      the Lanthony D-15 test does not appear to be markedly impaired.

PMID- 9615963
TI  - [Aneurysm of the cystic artery as a rare cause of hemobilia].
AB  - A 52-year old woman was admitted to the hospital because of upper abdominal pain
      and hematemesis. Laboratory parameters showed marked cholestasis. Endoscopic
      retrograde cholangiopancreatography (ERCP) lead to the diagnosis of hemobilia. CT
      scan and angiography revealed an aneurysm of the cystic artery as the cause of
      hemobilia. Cholecystectomy was performed because of concomitant cholecystitis.
      Anatomical examination confirmed clinical diagnosis.

PMID- 9615964
TI  - [Gazing and seeing, observing and recognizing: the eye motiv in literature].

PMID- 9615965
TI  - [Urinary pyridinoline as a possible marker of tumor-induced osteolysis].

PMID- 9615966
TI  - [Conservative vs. surgical therapy of first traumatic dislocation of the shoulder
      joint].

PMID- 9615967
TI  - [Thoracoscopic release in scoliosis].

PMID- 9615968
TI  - [Why was electrostimulation therapy of scoliosis discontinued?].

PMID- 9615969
TI  - [Development of arthrosis caused by meniscus transplantation?].

PMID- 9615970
TI  - [Quality assurance in endoprosthetics].

PMID- 9615971
TI  - [Quality assurance in endoprosthetics].
AB  - BACKGROUND: To evaluate the level of documentation as an instrument of ongoing
      quality management in arthroplasty, a questionnaire was created on this subject,
      which concentrated on structural and process indicators. METHODS: A total of 908
      questionnaires was sent to orthopedic and trauma departments in Austria, Germany
      and Switzerland and were evaluated anonymously. RESULTS: The quota of return was
      54% in Switzerland, 47% in Austria and 25% in Germany. The waiting period for an
      arthroplasty is much less in Switzerland and in Germany than in Austria. Only 40%
      of patients receive forms for informed consent. Documentation is seldomly
      standardized thus making comparison virtually impossible. Surgical planning is
      usually done with templates in Germany and Austria, in Switzerland with drawings.
      Prosthesis passports are predominately used by orthopedic departments. The data
      regarding complication rates and infections are not analyzed at regular intervals
      (max. 30%) and corrective measures are rarely implemented. CONCLUSION:
      Documentation is the basic instrument of quality management and requires
      completeness (totality) and plausibility of the datas. It is of great importance
      that evaluated data are analyzed and consequences are taken. The primary aim of
      quality assurance is to identify problems that adversely affect quality in order
      to develop and implement process sequences for the improvement of patient care
      and management.

PMID- 9615972
TI  - [10 years results with the corund-blasted Zweymuller titanium alloy threaded
      acetabular cup].
AB  - The Zweymuller threaded acetabular cup is cone-shaped with a corundblasted
      surface to allow bony ingrowth. We do not know any report of a ten-years follow
      up of this cup. 90 consecutive patients with 92 primary THR of this system are
      investigated on average of 10.25 years of implantation. 6 patients were lost of
      follow-up. 36 patients had died without any signs or symptoms of aseptic
      loosening. 48 patients with 50 hips were accepted in the retrospective study. We
      observed 5 aseptic loosenings of the cup and 4 aseptic loosenings of the stem. A
      total of 11 additional operations was necessary in these 90 patients including
      two explantations due to acute deep infection. The Harris hip score was 76.5
      points on average. Patients with disabling diseases reached only 62.3 points.
      Compared to the remaining patients with 88.3 points the difference was highly
      significant. Revision surgery of the acetabular component was not hampered by the
      conical reamed acetabular bone stock. No massive polyethylen wear occurred in
      this period. After ten years the survival rate was 92.6% for the cup and 90.6%
      for the stem respectively. This survival rate is superior to similar threaded
      cups. We conclude that the roughened surface of the titanium cup leads to a
      significant improvement of long-term stability.

PMID- 9615973
TI  - [Comparative periprosthetic bone density measurements of the proximal femur shaft
      using dual energy x-ray absorptiometry (DEXA) with experimental "Press Fit
      gliding Stem Prosthesis"].
AB  - PROBLEM: Periprosthetic bone atrophy caused by stress shielding is one of the
      problems of non-cemented femoral stems of hip arthroplasty. Stress shielding and
      thus the loss of bone mass and their dissemination in the proximal part of the
      femur of conventional non-cemented femoral stems depends on stiffness (E-modules
      of the material and the geometry) of the implant and on the bonding between
      implant and bone. All currently implanted non-cemented femoral stems lead to
      proximal bone loss which goes up to 40-50% of the original bone mineral content.
      The senior author (E. M.) developed a femoral stem (Press Fit-Gliding Stem PFGS)
      which shifts relative movements of force-transmission from the bone-implant
      interface into the interior of the prosthetic system (Inner Bearing-System) and
      which only transfers forces proximal into the femur. METHOD: The examinations
      were made in 21 patients between 1 and 6 years after implantation of a Press Fit
      Gliding Stem compared with a normal contralateral femur (12), with bilateral PFGS
      (3) and other bilateral arthroplasty (6). RESULTS: In all 21 patients supplied
      with a PFGS an increase of bone mineral content (BMC) and bone mineral density
      (BMC) in zone 7 as well as a marked smaller deviation around the mean value in
      all zones respectively could be noticed. CONCLUSIONS: With the Dual Energy X-ray
      Absorptiometry (DEXA)-measurement of bone mineral content (BMC) and bone mineral
      density (BMD) in all zones according to Gruen could be shown that it is not only
      possible with regard to a favorable force transmission to avoid the inevitable
      bone atrophy but on the contrary to induce an increase of bone at the point of
      local force transmission that is in the region of the calcar femorale (zone 7).
      CLINICAL RELEVANCE: The Press Fit-Gliding Stem is still in the clinical test
      program.

PMID- 9615974
TI  - [An in vitro model for producing femoral fractures and for the study of primary
      stability of cerclage].
AB  - PURPOSE: Intraoperative femoral fracture is a well recognized intraoperative
      complication of cementless total hip arthroplasty (THA). This study was designed
      to establish an in-vitro model for initiation of fractures of the femur in
      cementless THA and to assess the effect of fracture fixation by cerclage wiring
      using steel wire (Protasul). METHODS: Ten human femur specimens were studied.
      Longitudinal cracks were created by pressing a well fixed conical stem deeper
      into the femur in a material testing machine. RESULTS: The force necessary to
      propagate a longitudinal crack in the femur was 1915 N to 9288 N (median 6531 N).
      This forces are according to 3 to 15 times (median 11 times) body weight. There
      was no difference of force between left and right femurs from the same individual
      (U-test). The femoral cortex fractured in 5 cases ventrally, in 6 cases medially
      and in 1 case laterally. After monofile cerclage wire application the force
      required to press prosthesis 5 mm deeper into the medullary canal was 0.3 to 2.7
      times body weight. After monofile cerclage wire application pressing in the
      prosthesis 30 mm needed 1.8 to 8.1 times body weight. CONCLUSIONS: During
      insertion of a conical stem the orthopaedic surgeon should look for fractures of
      the medial cortex of the femur which is the most frequent location for fractures.
      This in-vitro model provides a reproductable method for the initiation and
      propagation of longitudinal femoral fractures in press-fit noncemented THA system
      and to assess the effect of fracture fixation in the form of cerclage wiring.

PMID- 9615976
TI  - [MRI-controlled outcome after core decompression of the femur head in aseptic
      osteonecrosis and transient bone marrow edema].
AB  - PURPOSE: We evaluated the signal changes of avascular necrosis and transient bone
      marrow oedema before and after core decompression of the femoral head to deduce
      prognostic factors for this operative procedure. METHOD: 38 to 40 cases with core
      decompression (35 patients, medium age 44 years) were analysed with a mean follow
      up time of 26 months. Preoperatively patients were staged by the ARCO
      classification. MR-images were judged in accordance to the criteria of Mitchell
      and Steinberg. The clinical outcome was analysed according to the hip index of
      Merle D'Aubigne. RESULTS: All hips with transient bone marrow oedema showed
      normal signal patterns at an average of 3 months after core decompression. In
      stage I and II, all patients with a preoperative necrosis area less than 30% of
      the femoral head showed a reduction of the necrotic zone and good clinical
      results. An unchanged or progressive appearance was observed in necrotic lesions
      with more than 30% head involvement. Because of failure a renewed operation had
      to be done in all patients with stage III and IV. CONCLUSION: In the case of
      transient bone marrow oedema, a restitutio ad integrum can be achieved with core
      decompression. In stage I and II of avascular necrosis, the successful outcome
      depends on the lesion size of the femoral head. Necrotic lesions less than 30%
      seem to have the best prognosis. In stage III and IV, core decompression cannot
      be recommended.

PMID- 9615975
TI  - [Reperfusion capacity of the femur head after ischemia--an experimental study].
AB  - PURPOSE OF THE STUDY: The aim of this study was to evaluate bone blood flow of
      the proximal femur during experimentally induced ischemia and to document the
      ability of epiphyseal and metaphyseal reperfusion. METHODS: 11 pigs (danish
      landrace) were used to investigate the effect of tamponade by increased joint
      pressure (Dextran 70) on the perfusion of the femoral head. Additional 8 pigs
      were used as control. The blood flow in the hip joint was studied by means of the
      microsphere technique. The flow was determined before, during and after
      intraarticular pressure increase. With the "radioactive tracer microsphere"
      method the blood flow of the epiphysis, metaphysis and proximal femoral
      corticalis could be measured. RESULTS: In the epiphyseal femoral head the initial
      blood flow rate, 11.7 ml/min/100 g, was not significant different from that of
      the control side (11.1 ml/min/100 g). The blood flow decreased in the ischemic
      phase to 1.8 ml/min/100 g followed by reperfusion to 13.5 ml/min/100 g (p <
      0.01). The bone blood flow of reperfusion was not significant different from that
      of the initial blood flow rate but in 2 cases a "blow out" of the epiphyseal bone
      blood flow was seen. The proximal femoral metaphysis showed the highest of the
      measured intraosseous flow rates (17.9 resp. 23.3 ml/min/100 g). During ischemia
      and reperfusion of the epiphysis bone blood flow of the metaphysis remained the
      same. The proximal femoral corticalis showed the lowest of the measured
      intraosseous flow rates. The operated (10.1 ml/min/100 g) and contralateral hip
      side (11.7 ml/min/100 g) showed no significant differences in the initial blood
      flow rate. During ischemia and reperfusion the blood flow of the proximal
      corticalis showed no significant difference to the initial blood flow
      corresponding to the metaphysis. CONCLUSIONS: Our study demonstrates disturbances
      of the circulation of different regions of the femoral head during intraarticular
      pressure increase and following pressure decrease of the growing pig. 2 "blow
      outs" document a vulnerable proximal epiphysis already after a 6-hour ischemia.
      Additional minor "bone quality" in cases of certain diseases (kidney
      transplantation, leukemia) and special administration of drugs (corticosteroids)
      seem to create an additional vulnerability of the proximal femoral head. The
      experiment proves to be a reliable model for decreasing the blood flow of the
      growing epiphysis temporarily and to document the beginning of normal
      reperfusion. With this model it is possible to examine the vulnerability of the
      epiphyseal perfusion after different diseases and under the influence of
      different medication.

PMID- 9615977
TI  - [Intertrochanteric rotational osteotomies in idiopathic femur head necrosis-
      comparison of different procedures].
AB  - PROBLEM: The aim of this study was to to compare different intertrochanteric
      osteotomies for avascular necrosis of the hip and to discuss it in the light of
      improving results of total hip arthroplasty. METHOD: 106 patients with diagnosis
      of avascular necrosis of the hip underwent an intertrochanteric osteotomy. During
      an interval of 14 years a total of 63 flexion osteotomies (partly combined with
      varisation or valgisation), 29 rotational osteotomies, 13 varisation osteotomies,
      8 medializing osteotomies and 2 extension osteotomies were performed. The mean
      follow-up period for all osteotomies was 69 months (13-180 months). RESULTS: At
      the time of follow-up investigation, already 75.9% of patients with a rotational
      osteotomy had received a total hip arthroplasty, comparing to only 34.9%
      following flexion osteotomy. The Harris Hip Score of the remaining 7 rotational
      osteotomies was 86.5, for the 41 flexion osteotomies the HHS rated 73.8 points. A
      high incidence of early complications (55.2%) was seen after rotational
      osteotomies, compared to 17.5% after flexion osteotomy. For all osteotomies a
      high correlation between the size of the necrotic area (radiographic ap + axial
      necrotic sector) and the risk of failure can be demonstrated. Sugioka's
      rotational osteotomy showed only a very low probability of survival after 5 years
      (15.9%), in contrast to the flexion osteotomy (5a: 71.6%, 10a: 49.6%). The
      subgroup of flexion osteotomy with a necrotic sector < 180 degrees achieves the
      best survival probability of 89.2% after 5 years and 60.7% after 10 years.
      CONCLUSION: The indication for intertrochanteric osteotomies for avascular
      necrosis of the hip has to be discussed critically today. Good results can only
      be expected with small necrotic areas using the flexion osteotomy. It was
      impossible to obtain satisfactory long-term results with the rotational osteotomy
      due to a high risk of complications.

PMID- 9615978
TI  - [Long-term results of tibial head osteotomy].
AB  - QUESTION: Long term outcome after high tibial osteotomies is essential too for
      the actual indication of these procedures. Complications and success rate were
      analysed in our patients in order to find out predictive determinants for the
      outcome. METHOD: 200 high tibial osteotomies were performed at the Orthopaedic
      clinic of Kiel University between 1974 and 1983. 148 knees (74%) could be
      reviewed with an average follow-up period of 10 years. 103 knees were personally
      examined, 45 cases were investigated by questionnaire. RESULTS: 74% were content
      with the result of the operation. Deterioration of complaints could be stopped in
      many cases, although the radiographic changes were not parallel to subjective
      relief of pain. The survival rate without implantation of knee prostheses was 96%
      12 years postoperatively. In 10 cases which had continuous complaints knee
      arthroplasties were performed one to two years after high tibial osteotomy. 6
      knees required additional surgery because of loss of correction. Serious
      complications did not occur apart from one peroneal nerve palsy and two deep
      though completely healed infections. CONCLUSION: High tibial osteotomy in a
      modified procedure according to Coventry thus guarantees long term success with
      low risk of failure only.

PMID- 9615979
TI  - [Position of the patella after knee endoprosthesis. A by radiology and
      computerized tomography controlled study].
AB  - The position of the Patellaimplant of 35 total knee arthroplasties (PCA) in
      regard to the other components, to patellar ligament and to correction of axis
      was analysed. The position of the patella was investigated with an average follow
      up of 38 months both radiologically and by computed tomography. A lateralisation
      of 4 mm on average and a lateral tilting of 4 degrees on average were found. The
      lateralisation of the patella in 30 and 60 degrees defilee radiographs
      demonstrated a significant dependence on the correction angle into valgus
      position. In lateral view and computed tomography the tilting of the patella is
      also dependent on the length of the ligamentum patellae. To avoid lateralisation
      and tilting of the patella in case of caudal position of the patella and a high
      intraoperative degree of correction into valgus position, careful check of the
      patella position is recommended in order to lateral release or medial capsular
      shift.

PMID- 9615980
TI  - [Bilateral habitual fibula head dislocation].
AB  - Dislocation of the fibular head is rare. In most of the cases a trauma caused by
      sports activity, sometimes associated with a tibia fracture, is described. Only a
      few publications exist about habitual dislocation of the fibular head without
      history of trauma. This article reports a case of bilateral habitual
      anterolateral dislocation of the fibular head in a 17-year-old female. There was
      no information about a neurological or other disease and no sign of generalized
      ligamentous laxity. Because of marked symptoms with severe pain after each
      sensation of dislocation which appeared several times a day, the patient was
      treated by using a part of the biceps tendon for fixation of the reduced fibular
      head.

PMID- 9615982
TI  - [Complications, side-effects and contraindications in the use of medium and high
      energy extracorporeal shock waves in orthopedics].
AB  - INTRODUCTION: Possible complications and side effects using extracorporeal shock
      waves for orthopaedic diseases should be evaluated. METHOD: Since 1993 we
      prospectively evaluated the complications and adverse effects applying
      extracorporeal shockwaves for orthopaedic diseases. Within three years 542
      lithotripsies in 276 patients were made. 190 patients were treated because of
      calcifying tendinitis, 34 for epicondylitis and 52 suffering from a plantar heel
      spur. RESULTS: In 216 cases we could recognize small superficial hematomas, 4
      hyperventilations and in 3 cases a blood pressure elevation over 200 mmHg. Two
      cases of high blood pressure showed data over 200 mmHg without other clinical
      symptoms. They were of transitory nature during therapy. In one case we had to
      treat a hypertension crisis within the first 3 hours after therapy. Today the
      application of shockwaves in the thoracic region or lung, coagulopathies or
      anticoagulant medicine, pregnancy and the use at nerval or vascular structures
      represent an absolute contraindication. When using extracorporeal shock waves for
      bone lithotripsy, bone tumors, bone infection or infected pseudarthrosis and the
      application at growth plates in children and young adults represent an absolute
      contraindication. CONCLUSION: In general lithotripsy has only minor complications
      when it is used accurate.

PMID- 9615981
TI  - [Symptomatic low-energy shockwave therapy in heel pain and radiologically
      detected plantar heel spur].
AB  - QUESTION: The long-term analgetic effect of low-energetic shock-wave therapy in
      heel spur for two different numbers of applicated impulses is investigated.
      METHODS: 50 patients with recalcitrant heel pain and a plantar calcaneal spur on
      the X-ray received in a controlled, prospective and randomized study low
      energetic extracorporal shock-wave-therapy. The first group received 3 x 500
      impulses and the second group 3 x 100 impulses of 0.08 mJ/mm2 with an
      experimental device. The follow-up was 1 1/2, 3 and by telephone after 12 months.
      RESULTS: There was clear improvement and relief of pain in both groups on manual
      pressure and while walking and an increase of the pain-free walking ability from
      10 minutes before the treatment to 2 and 3 hours respectively after 12 months. We
      saw a significantly better results after the treatment with 3 x 500 impulses.
      CONCLUSION: The extracorporal shock-wave therapy is an effective treatment in
      refractory heel pain. An amount of at least 3 x 500 impulses in the low energetic
      treatment is useful.

PMID- 9615983
TI  - [Repositioning injuries of nerve root L5 after surgical treatment of high degree
      spondylolistheses and spondyloptosis--in vitro studies].
AB  - Temporary or persistent paralysis of the fifth lumbar nerve root have been
      frequently reported as complications following reposition of high degree
      spondylolisthesis. According to an outcome analysis of sixty-four patients, we
      found an increased incidence of motor damages after reduction of Meyerding degree
      four anterolisthesis or spondyloptosis. There were no signs of intradural root
      compression or nerve injury tracable. In order to detect extraforaminal
      strictures, the anatomic course of the lumbosacral plexus and its relation to
      neighbouring structures, especially pelvivertebral connective tissue junctions
      were recorded in cadavric measurements. Beside an number of variations in origin
      and course of the iliolumbar ligament complex, we observed a junction between os
      sacrum and the anterior part of the fifth lumbar vertebrae in 14/30 specimen,
      constantly running anterior to the fifth lumbar nerve root. In addition the nerve
      was fixed to the sacral periostium a few centimeters distal this crossing in
      about 20% of all cases. Pathophysiological effects were measured in reposition
      trials, using a continuous pressure monitoring system. A reposition of more than
      20 mm resulted in a perineural pressure > 30 mmHg. This caused a nerve fiber
      deformation at the edge of the compressed nerve segment. Increased pressure leads
      to a nodular displacement of perineural fat as well as intraneural fascicles.

PMID- 9615984
TI  - Acute Halon (bromochlorodifluoromethane) toxicity by accidental and recreational
      inhalation.

PMID- 9615985
TI  - Disparities in CME costs among specialties.

PMID- 9615986
TI  - Increases in pediatrics residency applications.

PMID- 9615987
TI  - Institutionalized faculty development program.

PMID- 9615988
TI  - Role of computers at community sites.

PMID- 9615989
TI  - Tracking students' career interests following a generalist preceptorship.

PMID- 9615990
TI  - Physiological Society Symposium: Glucose Transport: A Functional Approach. A
      tribute to W. F. Widdas.

PMID- 9615991
TI  - Relationships between local synaptic connections and orientation domains in
      primary visual cortex.

PMID- 9615992
TI  - [Nephroblastoma--Wilms' tumor].

PMID- 9615993
TI  - [Honors and prizes].

PMID- 9615994
TI  - [Vacuum occlusion: a new concept in treatment of soft tissue and bone
      infections].

PMID- 9615995
TI  - Hydration water molecules of nucleotide-free RNase T1 studied by NMR spectroscopy
      in solution.
AB  - The hydration of uncomplexed RNase T1 was investigated by NMR spectroscopy at pH
      5.5 and 313 K. Two-dimensional heteronuclear NOE and ROE difference experiments
      were employed to determine the spatial proximity and the residence times of water
      molecules at distinct sites of the protein. Backbone carbonyl oxygens involved in
      intermolecular hydrogen bonds to water molecules were identified based on 1J(NC)
      coupling constants. These coupling constants were determined from 2D-H(CA)CO and
      15N-HSQC experiments with selective decoupling of the 13C alpha nuclei during the
      t1 evolution time. Our results support the existence of a chain of water
      molecules with increased residence times in the interior of the protein which is
      observed in several crystal structures with different inhibitor molecules and
      serves as a space filler between the alpha-helix and the central beta-sheet. The
      analysis of 1J(NC) coupling constants demonstrates that some of the water
      molecules seen in crystal structures are not involved in hydrogen bonds to
      backbone carbonyls as suggested by crystal structures. This is especially true
      for a water molecule, which is probably hydrogen bonded by the protonated
      carboxylate group of D76 and the hydroxyl group of T93 in solution, and for a
      water molecule, which was reported to connect four different amino acid residues
      in the core of the protein by intermolecular hydrogen bonds.

PMID- 9615996
TI  - Automated backbone assignment of labeled proteins using the threshold accepting
      algorithm.
AB  - The sequential assignment of backbone resonances is the first step in the
      structure determination of proteins by heteronuclear NMR. For larger proteins, an
      assignment strategy based on proton side-chain information is no longer suitable
      for the use in an automated procedure. Our program PASTA (Protein ASsignment by
      Threshold Accepting) is therefore designed to partially or fully automate the
      sequential assignment of proteins, based on the analysis of NMR backbone
      resonances plus C beta information. In order to overcome the problems caused by
      peak overlap and missing signals in an automated assignment process, PASTA uses
      threshold accepting, a combinatorial optimization strategy, which is superior to
      simulated annealing due to generally faster convergence and better solutions. The
      reliability of this algorithm is shown by reproducing the complete sequential
      backbone assignment of several proteins from published NMR data. The robustness
      of the algorithm against misassigned signals, noise, spectral overlap and missing
      peaks is shown by repeating the assignment with reduced sequential information
      and increased chemical shift tolerances. The performance of the program on real
      data is finally demonstrated with automatically picked peak lists of human
      nonpancreatic synovial phospholipase A2, a protein with 124 residues.

PMID- 9615997
TI  - Pregnant women should routinely be offered HIV tests.

PMID- 9615998
TI  - UK experts will speed up work on cannabis.

PMID- 9615999
TI  - CJD no worse in Britain than elsewhere.

PMID- 9616000
TI  - Effectiveness of regional trauma systems. Wrong comparisons were made.

PMID- 9616001
TI  - Effectiveness of regional trauma systems. Data do not support conclusions.

PMID- 9616002
TI  - Management of dyspepsia in primary care. Antibiotic resistance is a problem.

PMID- 9616003
TI  - Management of dyspepsia in primary care. Dyspepsia subgroups are useful in
      determining treatment.

PMID- 9616004
TI  - Management of dyspepsia in primary care. Breath test is better than near patient
      blood tests.

PMID- 9616005
TI  - Tolerability of alendronate. Figures given in letter were prevalences, not
      incidences.

PMID- 9616006
TI  - Tolerability of alendronate. Manufacturer's comment.

PMID- 9616007
TI  - FDA approves heart laser treatment.

PMID- 9616008
TI  - Interferon beta produces only small benefits in multiple sclerosis.

PMID- 9616009
TI  - An ethical code for everybody in health care. A universal declaration of
      patients' rights is a complementary approach.

PMID- 9616010
TI  - An ethical code for everybody in health care. Patients should help to shape such
      a code.

PMID- 9616011
TI  - An ethical code for everybody in health care. The code should follow the moral
      principles of law abiding citizens.

PMID- 9616012
TI  - An ethical code for everybody in health care. Three crucial limitations need to
      be considered.

PMID- 9616013
TI  - An ethical code for everybody in health care. A universal code should start with
      basic human rights.

PMID- 9616014
TI  - An ethical code for everybody in health care. Hippocratic Oath translated into
      poetry.

PMID- 9616015
TI  - An ethical code for everybody in health care. The healer's promise.

PMID- 9616016
TI  - Accidental child poisoning. Child resistant packaging should be the legal
      requirement.

PMID- 9616017
TI  - Report on cleft lip and palate surgery. Disagreement between specialties was not
      impetus for study.

PMID- 9616018
TI  - Report on cleft lip and palate surgery. Surgeon's specialty is less important
      than training and experience.

PMID- 9616019
TI  - Report on cleft lip and palate surgery. Reaction from health professionals has
      been muted.

PMID- 9616020
TI  - Britain launches pilot screening programme for chlamydia.

PMID- 9616021
TI  - Parasites likely to have plagued Louis XIV.

PMID- 9616022
TI  - CF gene may protect against typhoid fever.

PMID- 9616023
TI  - Can students learn comparable clinical skills in general practice and hospital
      settings? Availability of resources may have been a key factor.

PMID- 9616024
TI  - Can students learn comparable clinical skills in general practice and hospital
      settings? Like should be compared with like in a randomised crossover trial.

PMID- 9616025
TI  - Compression ultrasonography for diagnosing deep vein thrombosis. Colour Doppler
      provides useful information.

PMID- 9616026
TI  - Compression ultrasonography for diagnosing deep vein thrombosis. Other tests
      should not be abandoned.

PMID- 9616027
TI  - Compression ultrasonography for diagnosing deep vein thrombosis. Venography is
      more accurate.

PMID- 9616028
TI  - Compression ultrasonography for diagnosing deep vein thrombosis. Protocol is
      safe.

PMID- 9616029
TI  - Compression ultrasonography for diagnosing deep vein thrombosis. Repeat testing
      is unjustified.

PMID- 9616030
TI  - Radon may account for one in 20 cases of lung cancer.

PMID- 9616031
TI  - Foot morbidity and exposure to chiropody. Study needs to address several issues.

PMID- 9616032
TI  - General practitioners' self assessment of knowledge. Knowledge gaps were
      identified by general practitioners.

PMID- 9616033
TI  - General practitioners' self assessment of knowledge. Testing can be valid only if
      questions are relevant to those tested.

PMID- 9616035
TI  - Mortality and distribution of income. Low relative income affects mortality.

PMID- 9616034
TI  - Preventing RhD haemolytic disease of the newborn. Services should be centralised
      for pregnancies affected by RhD haemolytic disease.

PMID- 9616036
TI  - Mortality and distribution of income. Widening income inequalities cause poorer
      health.

PMID- 9616037
TI  - Isospora thibetana N. sp. (Apicomplexa, Eimeriidae), a parasite of the Tibetan
      siskin (Serinus thibetanus = Carduelis thibetanus) (Passeriformes, Fringillidae).
AB  - Tibetan siskins are birds native to the Himalayan region often imported into
      Italy for commercial purposes. Fecal examination of 45 imported subjects with
      clinical signs of diarrhoea revealed the presence of a large number of coccidian
      oocysts. After sporulation, accomplished by mixing feces with 2.5% (w/v) aqueous
      K2Cr2O7 at room temperature (22 degrees C +/- 1 degree C), exogenous stages of an
      Isospora species were revealed. The oocysts of this Isospora are spherical, have
      a bilayered colorless wall, and average 23.24 microm x 23.05 microm; oocyst
      residuum and micropyle are absent, while an oval polar granule is rarely present.
      The elliptical sporocysts average 18.44 microm x 10.97 microm and the Stieda body
      protrudes slightly from the end of the sporocyst. A spherical sporocyst residuum,
      is present though it sometimes consists of scattered granules. The spindle-shaped
      sporozoites average 11.53 microm x 2.86 microm, and have two refractile bodies.
      The taxonomic position of the tibetan siskin is controversial. Some authors
      include this species in the genus Serinus, while others include it in the genus
      Carduelis. The coccidian species isolated from these tibetan siskins was, for
      this reason, compared with the Isospora species previously described both in the
      genus Carduelis and in the genus Serinus. As a result of this comparison a new
      species, Isospora thibetana, was named. In the intestine of dead subjects,
      oocysts were found only in the ileum where the mucosa was greatly thickened and
      presented a heavy leucocytic infiltration consisting mainly of lympho-monocytic
      cells. A similar infiltration was observed in liver and lungs as well.

PMID- 9616038
TI  - Enhanced separation of DNA sequencing products by capillary electrophoresis using
      a stepwise gradient of electric field strength.
AB  - The effect of the electric field strength gradient on the separation of DNA
      sequencing fragments was investigated. We demonstrate that the stepwise gradient
      of electric field improves the separation of DNA sequencing fragments more than
      500 bases in size and diminishes the analysis time for DNA sequencing of lager
      DNA fragments. The use of the electric field strength gradient induces an
      increase in the theoretical plate number as predicted by the theoretical
      formulation discussed in this paper.

PMID- 9616040
TI  - Characterization of interaction between cephalosporins and charged surfactants
      using capillary zone electrophoresis.
AB  - Capillary electrophoresis offers a new way of characterizing the interaction
      between surfactants and drugs. This interaction was studied using capillary zone
      electrophoresis (CZE). It was observed that addition of tetraalkylammonium
      bromide to the electrolyte buffer at different concentrations of dodecyl
      trimethylammonium bromide (DTAB) led to a change of the migration time (tm) and
      of the ionic mobility (mu) of cephalosporins. For quantitative evaluation, a
      physicochemical model was developed to calculate the aggregation constants (k)
      and the stoichiometric coefficients (m) between DTAB and cephalosporins. The
      relative standard deviation of the effective mobilities and of the EOF were
      estimated.

PMID- 9616039
TI  - Determination of chiral catabolites from S-[2-carboxyl-1-(1H-imidazol-4
      yl)ethyl]glutathione, a proposed metabolite of L-histidine, by capillary
      electrophoresis].
AB  - A new method for simultaneous determination of two diastereomers in each of S-[2
      carboxy-1-(1H-imidazol-4-yl)ethyl]-L-cysteine (I) and N-?S-[2-carboxy-1-(1H
      imidazol-4-yl)ethyl]-L-cysteinyl?glycine (II) was developed by electrophoresis
      using a neutral coated capillary with a separation buffer, pH 6.00, containing 80
      mM hydroxypropyl-beta-cyclodextrin at a field strength of 500 V cm-1 at 20
      degrees C. This method was applied to establishment of a catabolic pathway from S
      [2-carboxy-1-(1H-imidazol-4-yl)ethyl]glutathione (III) to compound I. Incubation
      of either of compound II diastereomers as an enzyme substrate with rat kidney
      homogenate in a phosphate buffer, pH 7.4, resulted in a formation of compound I
      only having correspondent configurations on asymmetric carbon atoms of its
      molecule with those of the substrate, i.e., no occurrence of isomerization in the
      catabolism. Additionally, little difference in action as the substrate between
      two diastereomers of compound II was found. When an equimolar mixture of two
      diastereomers of compound III was allowed to react with the homogenate in the
      presence of glycylglycine, two diastereomers of compound II were formed in the
      same yield with each other and then these were catabolized gradually to both
      isomers of compound I. These results suggest that compound II is a metabolic
      intermediate for the formation of compound I from compound III, and that little
      variation in reactivities of two diastereomers of compound III as well as
      compound II with enzymes is given by the difference in stereoisomerism of
      asymmetric carbon atoms on their molecules.

PMID- 9616041
TI  - Expression and enzymatic characterization of human glucose phosphate isomerase
      (GPI) variants accounting for GPI deficiency.
AB  - To elucidate the structure-function relationships in glucose phosphate isomerase
      (GPI), we established an expression system for human GPI as a fusion protein with
      glutathione S-transferase (GST) in E. coli. The GST-GPI fusion protein showed
      affinities for the substrates glucose 6-phosphate (G6P) and fructose 6-phosphate
      (F6P) similar to those of the native enzyme purified from human red blood cells
      (RBC). We expressed GPI cDNAs with four distinct disease-causing mutations and
      examined their enzymatic characteristics. Although each mutation caused reduced
      thermal stability, an amino acid substitution Thr-5-->Ile (T5I) exhibited marked
      thermal instability, suggesting that the amino-terminal of GPI is important for
      enzymatic stability. Thr-224 seemed not to be an essential residue, since the
      amino acid substitution Thr-224-->Met (T224M) showed normal substrate affinity in
      spite of a slight decrease in both specific activity and thermostability. Gln-343
      and Asp-539 have been shown to be in close proximity to the putative catalytic
      sites, and the present study showed that both Gln-343-->Arg (Q343R) and Asp-539-
      >Asn (D539N) caused impaired substrate affinity; Q343R showed high Km for both
      G6P and F6P, whereas D539N showed significantly decreased affinity only for F6P.
      These results suggest that not only reduced enzymatic stability but also impaired
      kinetics may disturb RBC metabolism of the GPI variants associated with
      hereditary hemolytic anemia.

PMID- 9616043
TI  - Equine Embryo Transfer IV. Proceedings of the 4th International Symposium on
      Equine Embryo Transfer. Reims, France, 16-18 January 1997.

PMID- 9616042
TI  - Geographic variance in the frequency of the t(14;18) translocation in follicular
      lymphoma: an Israeli series compared to the world.
AB  - It has been suggested that differences in the frequency of the t(14;18)
      translocation in follicular lymphoma might explain ethno-geographic variation in
      the incidence of these tumors. We tested Israeli follicular lymphoma patients for
      the frequency of the t(14;18) translocation, and reviewed the published
      literature, comparing the frequency in our series with data from different parts
      of the world. Tissue specimens from 36 Israeli follicular lymphoma patients were
      tested for presence of the translocation by PCR amplification of the MBR
      breakpoint. Twenty-two of the 36 patients (61%) tested positive. A systematic
      search of the literature yielded 35 papers reporting the frequency of the
      t(14;18) translocation in follicular lymphoma. We analyzed cytogenetic data and
      molecular data separately. For each method, data were pooled from all studies
      within each of three geographical regions - USA, East Asia and Europe. Pooled
      data from cytogenetic studies show a low frequency of the translocation in the
      Far East (38%) compared to the USA (71%), with an intermediate frequency found in
      Europe (61%). Molecular studies show a similar frequency of the translocation in
      the Far East and Europe, significantly lower than the frequency in pooled data
      from American studies. The frequency in our Israeli series is relatively high,
      comparable to that detected in the USA. We suggest that the apparent geographical
      differences we describe are unlikely to be caused by a difference in the biology
      of the tumor, and are more likely due to technical and methodological factors. We
      conclude that it is unlikely that differences in the frequency of the t(14;18)
      translocation explain the difference in the epidemiology of lymphoma between East
      and West.

PMID- 9616044
TI  - Databank of 3-dimensional structures of lectins.

PMID- 9616045
TI  - Paleoanthropology Society meetings. Seattle, Washington,USA. 24-25 March 1998.
      Abstracts.

PMID- 9616047
TI  - Melioidosis in north Queensland.

PMID- 9616046
TI  - Organ transplants revisited.

PMID- 9616048
TI  - Measles vaccine, inflammatory bowel disease and pervasive developmental disorder:
      is there cause for concern?

PMID- 9616049
TI  - 7th International Symposium on Neural Regeneration. Pacific Grove, California,
      USA. December 10-14, 1997. Abstracts.

PMID- 9616050
TI  - [Hand surgery: information services on the internet].
AB  - The Internet provides hand surgeons with a powerful tool to exchange and gather
      information on an international level. Commercial and non-profit services are
      offered to disseminate knowledge of hand surgery. The success will depend on the
      number of active participants who use these new media. This paper gives an idea
      of the possibilities offered by already existing services for and by hand
      surgeons.

PMID- 9616051
TI  - Growth and survival of protozoa isolated from a tannery effluent.
AB  - Industrial effluent from a tannery was used for the growth of algae in a medium
      containing various inorganic salts. Growth of algal cells became visible after 7
      d. Two species of protozoa were observed to proliferate in the algal culture
      containing no organic supplement in the medium. The culture was kept bacteria
      free by the use of antibiotics and was perpetuated for at least 150 d with no
      decline in the protozoan population. Efficient growth of protozoa in a culture of
      algae elucidated new modes of nutrition in protozoa. Cr(VI) was added to the
      medium to check the resistance of algae and protozoa against this heavy metal.
      Protozoa showed different degrees of resistance. The results indicate the
      importance of algae and protozoa in the process of bioremediation.

PMID- 9616052
TI  - Is the malaria diagnosis expensive?
AB  - Malaria remains the most important of the tropical diseases, widespread
      throughout the tropics, but also occurring in many temperate regions. The disease
      causes a heavy toll of illness and death, among children in endemic areas. It
      also poses a risk to business travellers, tourists and immigrants and imported
      cases of malaria are increasingly seen in non-endemic areas. We discuss here how
      microscopical diagnosis is essential for identifying Plasmodium species
      responsible of the infection and discarding possible mixed infections. Thus, a
      correct treatment can be administered in 30 min, avoiding secondary stays and
      saving important amounts of money. Problems of drug resistance have to be
      distinguished from those arising due to erroneous diagnosis.

PMID- 9616053
TI  - Degradation of fenitrothion by Bacillus stearothermophilus adhering to silica.
AB  - B. stearothermophilus strain AG-49, when cultivated in mineral medium in the
      presence of silica (SA), adhered to SA. Adhesion depended on age of culture,
      contact time and glucose concentration of the culture medium. Mid-exponential
      phase culture (5 h) required minimum contact time (30 min) for maximum adhesion.
      0.6% glucose concentration was optimum. Quantitative variation in protein and
      saccharide extractable in sodium chloride and sodium dodecyl sulfate (SDS) was
      observed. Five % degradation of fenitrothion by adherent B. stearothermophilus
      could be achieved in 4 d.

PMID- 9616054
TI  - Experimental biofilm and its application in malathion degradation.
AB  - Mixed bacterial culture consisting of three different strains of Micrococcus sp.
      (AG 36, AG 94 and AG 98) and two strains of Pseudomonas sp. (AG 7 and AG 52) and
      its individual components was passed through a sand column and 25.5-92% of cell
      dry mass was found to be retained (adsorbed) on it. Incubation of sand soaked in
      mineral medium containing glucose as a sole carbon source resulted in formation
      of a biofilm with 1.2-2.5-fold increase in biomass. A 61% degradation of
      malathion by the mixed culture biofilm could be achieved in 4 d.

PMID- 9616055
TI  - Comparison of static and shake culture in the decolorization of textile dyes and
      dye effluents by Phanerochaete chrysoporium.
AB  - Decolorization of several dyes (Red HE-8B, Malachite Green, Navy Blue HE-2R,
      Magenta, Crystal Violet) and an industrial effluent with growing cells of
      Phanerochaete chrysosporium in shake and static culture was demonstrated. All the
      dyes and the industrial effluent were decolorized to some extent with varying
      percentages of decolorization (20-100%). The rate of decolorization was very
      rapid with Red HE-8B, an industrial dye. Decolorization rates for all the dyes in
      static condition were found to be less than the shake culture and also dependent
      on biomass concentration.

PMID- 9616057
TI  - 11th National Institute of Mental Health International Conference on Mental
      Health Problems in the General Health Care Sector. Washington, DC, USA. September
      5-6, 1997. Abstracts.

PMID- 9616056
TI  - Screening of white-rot fungi for their ability to mineralize polycyclic aromatic
      hydrocarbons in soil.
AB  - Soil samples from an agricultural field contaminated with 10 ppm 14C
      benz(a)anthracene in glass tubes were brought into contact with cultures of wood
      rotting fungi, precultivated on wheat straw substrate. Forty-five strains of
      white-rot fungi and four brown-rot fungi were tested for their ability to
      colonize the soil and to mineralize 14C-benz(a)anthracene to 14CO2 within a 20
      week incubation time. Twenty-two white-rot fungi and all brown-rot fungi were
      unable to colonize the soil. Twenty-three strains of white-rot fungi, all
      belonging to the genus Pleurotus, colonized the soil. During the experiment the
      non-colonizing fungi and their substrate disintegrated more and more to a
      nonstructured pulp from which water diffused into the soil. The same phenomenon
      was observed in the control which contained only straw without fungus and
      contaminated soil. In samples with colonizing fungi the substrate as well as the
      mycelia in the soil remained visibly unchanged during the entire experiment.
      Surprisingly, most samples with fungi not colonizing the soil and the control
      without fungus liberated between 40 and 58% of the applied radioactivity as 14CO2
      whereas the samples with the colonizing fungi respired only 15-25% as 14CO2. This
      was 3-5 times more 14CO2 than that liberated from the control (4.9%) which
      contained only contaminated soil without straw and fungus. A similar result was
      obtained with selected colonizing and noncolonizing fungi and soil contaminated
      with 10 ppm 14C-pyrene. However, in pure culture studies in which 14C-pyrene was
      added to the straw substrate, Pleurotus sp. (P2), as a representative of the
      colonizing fungi, mineralized 40.3% of the added radioactivity to 14CO2. The
      noncolonizing fungi Dichomitus squalens and Flammulina velutipes liberated only
      17.2 or 1.7%, respectively, as 14CO2. These results lead to the hypothesis that
      the native soil microflora stimulated by the formed products of straw lysis is
      responsible for high degradation rates found with noncolonizing fungi.

PMID- 9616058
TI  - Cervical spine injury - quadriplegia.

PMID- 9616060
TI  - Carrell-Krusen Symposium. Dallas, Texas, USA. February 26-27, 1998.

PMID- 9616061
TI  - Lichen sclerosus thyroid disease.

PMID- 9616062
TI  - Screening for diabetes in pregnancy.

PMID- 9616063
TI  - Conflict of interest in the debate over calcium-channel antagonists.

PMID- 9616064
TI  - Conflict of interest in the debate over calcium-channel antagonists.

PMID- 9616065
TI  - Conflict of interest in the debate over calcium-channel antagonists.

PMID- 9616066
TI  - Treatment of chronic anal fissure.

PMID- 9616067
TI  - Genetic abnormalities in synovial sarcoma.

PMID- 9616068
TI  - Fetal sex and hemolytic disease from maternal red-cell alloimmunization.

PMID- 9616069
TI  - Daclizumab to prevent acute rejection in renal transplantation.

PMID- 9616070
TI  - Vancomycin and priapism.

PMID- 9616071
TI  - Case 3-1998: tuberculous peritonitis.

PMID- 9616072
TI  - Case 3-1998: tuberculous peritonitis.

PMID- 9616073
TI  - More on the obesity problem.

PMID- 9616075
TI  - Retraction statement. A new model of sustained atrial fibrillation in conscious
      dogs with pacing induced heart failure.

PMID- 9616074
TI  - Recommended dietary allowances in the Southeast Asian region: scientific basis
      and future direction. Symposium proceedings. Singapore, March 10-11, 1997.

PMID- 9616076
TI  - Technology-enabled education.

PMID- 9616078
TI  - Probing the biology of emotion.

PMID- 9616077
TI  - Allen Roses: from 'street fighter' to corporate insider.

PMID- 9616079
TI  - New probes open windows on gene expression, and more.

PMID- 9616081
TI  - Landscaping the cancer terrain.

PMID- 9616080
TI  - The expanding role of cell cycle regulators.

PMID- 9616082
TI  - Automating a mouse.

PMID- 9616083
TI  - Zeptomolar damage.

PMID- 9616084
TI  - Haeckel, embryos, and evolution.

PMID- 9616085
TI  - Demographic thinking.

PMID- 9616086
TI  - A good estrogen.

PMID- 9616087
TI  - Hubris and the human genome.

PMID- 9616088
TI  - Picking up the pace of sequencing.

PMID- 9616089
TI  - The power of the front page of The New York Times.

PMID- 9616090
TI  - German biotechs form gene venture.

PMID- 9616091
TI  - [Mefloquine: neuropsychiatric adverse effects are often severe and persistent
      long after withdrawal of the drug].

PMID- 9616092
TI  - [Patient-oriented, risk adjusted tumor after-care in patients with colorectal
      carcinoma].

PMID- 9616093
TI  - [On the 90th anniversary of the birth of V. N. Chernigovskii].

PMID- 9616094
TI  - Genetic and Environmental Determinants of Copper Metabolism. Proceedings of an
      international conference. Bethesda, Maryland, USA. March 18-20, 1996.

PMID- 9616095
TI  - Re: authors and authorship.

PMID- 9616096
TI  - Re: authors and authorship.

PMID- 9616097
TI  - Re: authors and authorship.

PMID- 9616098
TI  - Attribution of authors' contributions.

PMID- 9616099
TI  - Re: authors and authorship.

PMID- 9616100
TI  - Re: authors and authorship.

PMID- 9616101
TI  - Re: authors and authorship.

PMID- 9616102
TI  - Re: authors and authorship.

PMID- 9616103
TI  - Surgical Internet at a glance: volume III.

PMID- 9616104
TI  - Comparisons of three probability formulae for parentage exclusion.
AB  - Three general formulae calibrate the average capability of marker systems to
      dispute falsely reported pedigree records in uniparous species. The most familiar
      exclusion formula applies to paternity, although the same formula applies equally
      to maternity. Another formula faults the relationship of a single offspring with
      its putative parent; for example, where the genotype of the other parent is not
      available. The remaining formulae excludes both of the falsely recorded parents
      of a substituted offspring. Simplified forms of the three general formulae
      facilitate the calculation of maximal average exclusion values over a range of
      hypothetical markers. Allele frequency data on eight marker systems in horses
      provide practical examples. The exclusion values of the three formulae are
      compared.

PMID- 9616106
TI  - [Surgery video collection].

PMID- 9616105
TI  - Genetic linkage mapping of three anonymous ovine EST microsatellites: KD101,
      KD103 and KD721.

PMID- 9616107
TI  - Career by choice, not by chance.

PMID- 9616108
TI  - Writing an integrative review.

PMID- 9616109
TI  - Another look at a meta-analysis of zinc salts lozenges and the common cold.

PMID- 9616110
TI  - Cost of Troglitazone therapy.

PMID- 9616111
TI  - High-power directional emission from microlasers with chaotic resonators 
AB  - High-power and highly directional semiconductor microcylinder lasers based on an
      optical resonator with deformed cross section are reported. In the favorable
      directions of the far-field, a power increase of up to three orders of magnitude
      over the conventional circularly symmetric lasers was obtained. A "bow-tie"
      shaped resonance is responsible for the improved performance of the lasers in the
      higher range of deformations, in contrast to "whispering-gallery"-type modes of
      circular and weakly deformed lasers. This resonator design, although demonstrated
      here in midinfrared quantum-cascade lasers, should be applicable to any laser
      based on semiconductors or other high-refractive index materials.

PMID- 9616112
TI  - Role of the CLOCK protein in the mammalian circadian mechanism.
AB  - The mouse Clock gene encodes a bHLH-PAS protein that regulates circadian rhythms
      and is related to transcription factors that act as heterodimers. Potential
      partners of CLOCK were isolated in a two-hybrid screen, and one, BMAL1, was
      coexpressed with CLOCK and PER1 at known circadian clock sites in brain and
      retina. CLOCK-BMAL1 heterodimers activated transcription from E-box elements, a
      type of transcription factor-binding site, found adjacent to the mouse per1 gene
      and from an identical E-box known to be important for per gene expression in
      Drosophila. Mutant CLOCK from the dominant-negative Clock allele and BMAL1 formed
      heterodimers that bound DNA but failed to activate transcription. Thus, CLOCK
      BMAL1 heterodimers appear to drive the positive component of per transcriptional
      oscillations, which are thought to underlie circadian rhythmicity.

PMID- 9616113
TI  - Coupled 186Os and 187Os evidence for core-mantle interaction 
AB  - Osmium isotopic analyses of picritic lavas from Hawaii show enrichments in the
      osmium-186/osmium-188 ratio (186Os/188Os) of 0. 008 to 0.018%, relative to a
      chondritic upper mantle, that are positively correlated with enrichments in
      187Os/188Os of 5.4 to 9.0%. The most viable mechanism to produce these coupled
      186Os and 187Os enrichments is by addition of 0.5 to 1 weight percent of outer
      core metal to a portion of the D" layer and subsequent upwelling of the mixture.
      These data suggest that some plumes originate at the core-mantle boundary and
      that Os isotopes may be used to distinguish plumes derived from shallow versus
      deep mantle sources.

PMID- 9616114
TI  - Distribution of rock, metals, and ices in Callisto.
AB  - Radio Doppler data from a single encounter (C3) of the Galileo spacecraft with
      Callisto, the outermost Galilean moon of Jupiter, indicated that Callisto was
      probably undifferentiated. Now, similar data from a second encounter (C9)
      corroborate this conclusion, but more accurate data from a third encounter (C10)
      indicate that the rock and ice within Callisto have partially, but not
      completely, separated. Callisto may be differentiated into a rock-metal core less
      than 25 percent of Callisto's radius, an outer layer of clean ice less than 350
      km thick, and a middle layer of mixed rock and ice. Models in which ice and rock
      are mixed all the way to the center of Callisto are also consistent with the
      data.

PMID- 9616115
TI  - Detection of atomic deuterium in the upper atmosphere of Mars.
AB  - High-resolution spectroscopy of Mars' atmosphere with the Hubble Space Telescope
      revealed the deuterium Lyman alpha line at an intensity of 23 +/- 6 rayleighs.
      This measured intensity corresponds to HD/H2 = 1.5 +/- 0.6 x 10(-4), which is
      smaller by a factor of 11 than HDO/H2O. This indicates that fractionation of
      HD/H2 relative to that of HDO/H2O is not kinetically controlled by the rates of
      formation and destruction of H2 and HD but is thermodynamically controlled by the
      isotope exchange HD + H2O left and right arrow HDO + H2. Molecular hydrogen is
      strongly depleted in deuterium relative to water on Mars because of the very long
      lifetime of H2 (1200 years). The derived isotope fractionation corresponds to an
      estimate of a planetwide reservoir of water ice about 5 meters thick that is
      exchangeable with the atmosphere.

PMID- 9616116
TI  - Atmosphere-surface interactions on Mars: delta 17O measurements of carbonate from
      ALH 84001.
AB  - Oxygen isotope measurements of carbonate from martian meteorite ALH 84001
      (delta18O = 18.3 +/- 0.4 per mil, delta17O = 10.3 +/- 0.2 per mil, and Delta17O =
      0.8 +/- 0.05 per mil) are fractionated with respect to those of silicate
      minerals. These measurements support the existence of two oxygen isotope
      reservoirs (the atmosphere and the silicate planet) on Mars at the time of
      carbonate growth. The cause of the atmospheric oxygen isotope anomaly may be
      exchange between CO2 and O(1D) produced by the photodecomposition of ozone.
      Atmospheric oxygen isotope compositions may be transferred to carbonate minerals
      by CO2-H2O exchange and mineral growth. A sink of 17O-depleted oxygen, as
      required by mass balance, may exist in the planetary regolith.

PMID- 9616117
TI  - Localization of metastable atom beams with optical standing waves:
      nanolithography at the heisenberg limit 
AB  - The spatially dependent de-excitation of a beam of metastable argon atoms,
      traveling through an optical standing wave, produced a periodic array of
      localized metastable atoms with position and momentum spreads approaching the
      limit stated by the Heisenberg uncertainty principle. Silicon and silicon dioxide
      substrates placed in the path of the atom beam were patterned by the metastable
      atoms. The de-excitation of metastable atoms upon collision with the surface
      promoted the deposition of a carbonaceous film from a vapor-phase hydrocarbon
      precursor. The resulting patterns were imaged both directly and after chemical
      etching. Thus, quantum-mechanical steady-state atom distributions can be used for
      sub-0.1-micrometer lithography.

PMID- 9616118
TI  - Silacalix-
AB  - The synthesis of polyphosphinine macrocycles, which consist of a 16-membered ring
      with four phosphorus atoms (P4) and a 12-membered ring with three phosphorus
      atoms (P3), is described. Their high coordination ability is demonstrated by the
      quantitative synthesis of the rhodium and iridium cation complexes of the P4
      macrocycle and by quantitative synthesis of the W(CO)3 complex of the P3
      compound. Unlike the other available macrocyclic ligands bearing oxygen, sulfur,
      di- or tricoordinate nitrogen, and even tricoordinate phosphorus as ligating
      atoms, which are all essentially final sigma donors, these dicoordinate
      phosphorus-based macrocycles have strong pi-acceptor properties. Their use can be
      envisaged for the stabilization of negative oxidation states of transition metals
      or in reductive catalysis.

PMID- 9616119
TI  - High-Tc superconductors in the two-dimensional limit:
AB  - The free modulation of interlayer distance in a layered high-transition
      temperature (high-Tc) superconductor is of crucial importance not only for the
      study of the superconducting mechanism but also for the practical application of
      high-Tc superconducting materials. Two-dimensional (2D) superconductors were
      achieved by intercalating a long-chain organic compound into bismuth-based high
      Tc cuprates. Although the intercalation of the organic chain increased the
      interlayer distance remarkably, to tens of angstroms, the superconducting
      transition temperature of the intercalate was nearly the same as that of the
      pristine material, suggesting the 2D nature of the high-Tc superconductivity.

PMID- 9616120
TI  - Ribozyme-mediated repair of sickle beta-globin mRNAs in erythrocyte precursors.
AB  - Sickle cell anemia is the most common heritable hematological disease, yet no
      curative treatment exists for this disorder. Moreover, the intricacies of globin
      gene expression have made the development of treatments for hemoglobinopathies
      based on gene therapy difficult. An alternative genetic approach to sickle cell
      therapy is based on RNA repair. A trans-splicing group I ribozyme was used to
      alter mutant beta-globin transcripts in erythrocyte precursors derived from
      peripheral blood from individuals with sickle cell disease. Sickle beta-globin
      transcripts were converted into messenger RNAs encoding the anti-sickling protein
      gamma-globin. These results suggest that RNA repair may become a useful approach
      in the treatment of genetic disorders.

PMID- 9616121
TI  - The tetrameric structure of a glutamate receptor channel.
AB  - The subunit stoichiometry of several ligand-gated ion channel receptors is still
      unknown. A counting method was developed to determine the number of subunits in
      one family of brain glutamate receptors. Successful application of this method in
      an HEK cell line provides evidence that ionotropic glutamate receptors share a
      tetrameric structure with the voltage-gated potassium channels. The average
      conductance of these channels depends on how many subunits are occupied by an
      agonist.

PMID- 9616122
TI  - Closing the circadian loop: CLOCK-induced transcription of its own inhibitors per
      and tim.
AB  - The circadian oscillator generates a rhythmic output with a period of about 24
      hours. Despite extensive studies in several model systems, the biochemical mode
      of action has not yet been demonstrated for any of its components. Here, the
      Drosophila CLOCK protein was shown to induce transcription of the circadian
      rhythm genes period and timeless. dCLOCK functioned as a heterodimer with a
      Drosophila homolog of BMAL1. These proteins acted through an E-box sequence in
      the period promoter. The timeless promoter contains an 18-base pair element
      encompassing an E-box, which was sufficient to confer dCLOCK responsiveness to a
      reporter gene. PERIOD and TIMELESS proteins blocked dCLOCK's ability to
      transactivate their promoters via the E-box. Thus, dCLOCK drives expression of
      period and timeless, which in turn inhibit dCLOCK's activity and close the
      circadian loop.

PMID- 9616123
TI  - Teratogen-mediated inhibition of target tissue response to Shh signaling.
AB  - Veratrum alkaloids and distal inhibitors of cholesterol biosynthesis have been
      studied for more than 30 years as potent teratogens capable of inducing cyclopia
      and other birth defects. Here, it is shown that these compounds specifically
      block the Sonic hedgehog (Shh) signaling pathway. These teratogens did not
      prevent the sterol modification of Shh during autoprocessing but rather inhibited
      the response of target tissues to Shh, possibly acting through the sterol sensing
      domain within the Patched protein regulator of Shh response.

PMID- 9616124
TI  - Inhibition of a Mycobacterium tuberculosis beta-ketoacyl ACP synthase by
      isoniazid.
AB  - Although isoniazid (isonicotinic acid hydrazide, INH) is widely used for the
      treatment of tuberculosis, its molecular target has remained elusive. In response
      to INH treatment, saturated hexacosanoic acid (C26:0) accumulated on a 12
      kilodalton acyl carrier protein (AcpM) that normally carried mycolic acid
      precursors as long as C50. A protein species purified from INH-treated
      Mycobacterium tuberculosis was shown to consist of a covalent complex of INH,
      AcpM, and a beta-ketoacyl acyl carrier protein synthase, KasA. Amino acid
      altering mutations in the KasA protein were identified in INH-resistant patient
      isolates that lacked other mutations associated with resistance to this drug.

PMID- 9616125
TI  - Axonal swellings and degeneration in mice lacking the major proteolipid of
      myelin.
AB  - Glial cells produce myelin and contribute to axonal morphology in the nervous
      system. Two myelin membrane proteolipids, PLP and DM20, were shown to be
      essential for the integrity of myelinated axons. In the absence of PLP-DM20, mice
      assembled compact myelin sheaths but subsequently developed widespread axonal
      swellings and degeneration, associated predominantly with small-caliber nerve
      fibers. Similar swellings were absent in dysmyelinated shiverer mice, which lack
      myelin basic protein (MBP), but recurred in MBP*PLP double mutants. Thus, fiber
      degeneration, which was probably secondary to impaired axonal transport, could
      indicate that myelinated axons require local oligodendroglial support.

PMID- 9616126
TI  - Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor
      PTEN.
AB  - The tumor suppressor PTEN is a phosphatase with sequence similarity to the
      cytoskeletal protein tensin. Here the cellular roles of PTEN were investigated.
      Overexpression of PTEN inhibited cell migration, whereas antisense PTEN enhanced
      migration. Integrin-mediated cell spreading and the formation of focal adhesions
      were down-regulated by wild-type PTEN but not by PTEN with an inactive
      phosphatase domain. PTEN interacted with the focal adhesion kinase FAK and
      reduced its tyrosine phosphorylation. Overexpression of FAK partially antagonized
      the effects of PTEN. Thus, PTEN phosphatase may function as a tumor suppressor by
      negatively regulating cell interactions with the extracellular matrix.

PMID- 9616127
TI  - Entry of alphaherpesviruses mediated by poliovirus receptor-related protein 1 and
      poliovirus receptor.
AB  - A human member of the immunoglobulin superfamily was shown to mediate entry of
      several alphaherpesviruses, including herpes simplex viruses (HSV) 1 and 2,
      porcine pseudorabies virus (PRV), and bovine herpesvirus 1 (BHV-1). This membrane
      glycoprotein is poliovirus receptor-related protein 1 (Prr1), designated here as
      HveC. Incubation of HSV-1 with a secreted form of HveC inhibited subsequent
      infection of a variety of cell lines, suggesting that HveC interacts directly
      with the virus. Poliovirus receptor (Pvr) itself mediated entry of PRV and BHV-1
      but not of the HSV strains tested. HveC was expressed in human cells of
      epithelial and neuronal origin; it is the prime candidate for the coreceptor that
      allows both HSV-1 and HSV-2 to infect epithelial cells on mucosal surfaces and
      spread to cells of the nervous system.

PMID- 9616128
TI  - The Alzheimer's plaques, tangles and memory deficits may have a common origin.
      Part II: therapeutic rationale.
AB  - In the previous papers, we hypothesized that there could be an intracellular
      calcium deficit in the early phase of Alzheimer's disease (AD). In the present
      study, we consider, from this point of view, several long-lasting questions about
      AD, which include: why plaques and tangles are only found in the brain; why aging
      is the primary risk factor; why presenilins are so vulnerable in the disease; and
      why AD only affects the most delicate function of the brain. Although
      discrepancies and alternative views exist in many aspects of AD, it came to our
      attention that our hypothesis perhaps could offer a reasonable and coherent
      explanation, at least in part, to several such questions by the known biochemical
      principles. Based on the analyses, we discuss some controversies in therapeutic
      strategies.

PMID- 9616129
TI  - Alcohol and anesthetic mechanisms in genetically engineered mice.
AB  - Genetically engineered animals (e.g., transgenics, gene knockouts, gene knockins)
      are being utilized with increasing frequency to investigate the mechanisms of
      action of alcohol and anesthetics. By creating and analyzing animals that harbor
      precise, preplanned changes in candidate genes, researchers are rapidly making
      progress toward uncovering how these drugs exert their effects on the central
      nervous system to bring about their behavioral effects. Since these sedative /
      hypnotic agents are likely to exert their effects by altering neurotransmission,
      the majority of investigations to date have focused on neurotransmitter receptors
      and modulators of neurotransmission such as kinases.

PMID- 9616130
TI  - Role of lipoxygenases in breast cancer.
AB  - The interaction of growth factors such as epidermal growth factor (EGF) with
      their receptors on breast cancer cells can lead to the hydrolysis of
      phospholipids and release of fatty acids such as arachidonic acid which can be
      further metabolized by the lipoxygenase (LO) pathway. Several LO products have
      been shown to stimulate oncogenes and have mitogenic and chemotactic effects. The
      12-LO product, 12-hydroxyeicosatetraenoic acid (12(S)HETE), has been shown to
      play a key role in mediating several steps of the process of hematogenous
      metastasis and tumor cell adhesion. 12-LO can also be activated by several growth
      factors and inflammatory cytokines. A growing body of evidence suggests that
      specific metabolites of arachidonic and/or linoleic acid serve as central
      elements in signal pathways necessary for cell mitogenesis as induced by growth
      factors or oncogenic transformation. This review examines the role of LOs in
      breast cancer. The growth of breast cancer cells has been shown to increased by
      certain LO products and, LO pathway inhibitors could block the growth of some
      breast cancer cells. 12-LO activity and expression was increased in breast cancer
      tissues relative to the uninvolved normal tissue, and also in cultured breast
      cancer cells relative to normal breast cells. Treatment of the breast cancer cell
      line, MCF-7 cells, with epidermal growth factor (EGF), led to significant
      increases in 12-LO activity and expression. Thus, activation of the 12-LO pathway
      may play a key role in basal and EGF-induced breast cancer cell growth.

PMID- 9616131
TI  - Mechanism of Mycobacterium avium complex pathogenesis.
AB  - Mycobacterium avium complex (MAC) group of microorganisms are the most common
      opportunistic bacterial pathogens causing disseminated disease in HIV infected
      patients. These microorganisms are ubiquitous in nature, and are acquired by
      respiratory and oral routes. Pathogenesis of MAC depends on the ability of the
      organisms to colonize intestinal/respiratory mucosa, penetrate the protective
      barriers and resist intracellular killing by macrophages. Transient and
      reversible variation of colony morphology is one the characteristic feature of
      MAC that plays a significant role in the virulence and pathogenesis of these
      microorganisms. Isogenic colony variants of MAC differ in their virulence,
      susceptibility to antibiotics, stimulation of oxygen radicals and cytokines. The
      virulent smooth transparent colony variants are more frequently isolated from
      AIDS patients, more efficient in mucosal colonization, and adhere more
      efficiently to epithelial cells as compared to the less virulent smooth opaque
      variants. However, both the isogenic variants bind to the mucosal epithelial
      cells through the same multiple receptors. In addition, both the isogenic
      variants of MAC also bind to intestinal mucus through a single receptor. Study of
      the interaction of MAC with the host cells and characterization of MAC adhesins
      and host cell receptors facilitates the elucidation of the mechanisms involved in
      MAC pathogenesis.

PMID- 9616132
TI  - New perspectives on retinoblastoma family functions in differentiation.
AB  - Cell differentiation is a coordinated process that includes cell cycle exit and
      the expression of unique genes to specify tissue identity. The focus of this
      review is the recent progress in understanding the functions of the RB family
      (RB, p130,p107) in cell differentiation. Much work has focused on the functions
      of RB in G1 regulation. However, much evidence now suggests a diverse function in
      differentiation. For discussion, differentiation will be divided into three
      general steps: cell cycle exit, apoptosis protection, and tissue-specific gene
      expression. These processes are coordinated to provide the final and unique
      tissue characteristics. The RB family and targets such as E2F and HBP1 have
      functions in each step. While there is much knowledge on each separate step of
      differentiation, the mechanisms that coordinate cell cycle and tissue-specific
      events are still not known. New evidence suggests that this coordination contains
      both positive and negative regulation of tissue-specific gene expression. RB.
      p130, HBP1, and other proteins appear to have unexpected functions in regulating
      tissue-specific gene expression. The ubiquitous expressions of these proteins
      suggest membership in a new and general pathway to coordinate cell cycle events
      with tissue-specific gene expression during differentiation. The collective
      observations hypothesize the existence of a differentiation checkpoint to insure
      fidelity.

PMID- 9616133
TI  - Bernard-Soulier syndrome.

PMID- 9616134
TI  - Fusion of Huntingtin interacting protein 1 to platelet-derived growth factor beta
      receptor (PDGFbetaR) in chronic myelomonocytic leukemia with t(5;7)(q33;q11.2).
AB  - We report the fusion of the Huntingtin interactin protein 1 (HIP1) gene to the
      platelet-derived growth factor betareceptor (PDGFbetaR) gene in a patient with
      chronic myelomonocytic leukemia (CMML) with a t(5;7)(q33;q11.2) translocation.
      Southern blot analysis of patient bone marrow cells with a PDGFbetaR gene probe
      demonstrated rearrangement of the PDGFbetaR gene. Anchored polymerase chain
      reaction using PDGFbetaR primers identified a chimeric transcript containing the
      HIP1 gene located at 7q11.2 fused to the PDGFbetaR gene on 5q33. HIP1 is a 116-kD
      protein recently cloned by yeast two-hybrid screening for proteins that interact
      with Huntingtin, the mutated protein in Huntington's disease. The consequence of
      t(5;7)(q33;q11.2) is an HIP1/PDGFbetaR fusion gene that encodes amino acids 1 to
      950 of HIP1 joined in-frame to the transmembrane and tyrosine kinase domains of
      the PDGFbetaR. The reciprocal PDGFbetaR/HIP1 transcript is not expressed.
      HIP1/PDGFbetaR is a 180-kD protein when expressed in the murine hematopoietic
      cell line, Ba/F3, and is constitutively tyrosine phosphorylated. Furthermore,
      HIP1/PDGFbetaR transforms the Ba/F3 cells to interleukin-3-independent growth.
      These data are consistent with an alternative mechanism for activation of
      PDGFbetaR tyrosine kinase activity by fusion with HIP1, leading to transformation
      of hematopoietic cells, and may implicate Huntingtin or HIP1 in the pathogenesis
      of hematopoietic malignancies.

PMID- 9616135
TI  - Treatment of thrombocytopenia in chimpanzees infected with human immunodeficiency
      virus by pegylated recombinant human megakaryocyte growth and development factor.
AB  - Three chimpanzees experimentally infected with human immunodeficiency virus (HIV)
      developed significant chronic thrombocytopenia after 5, 4, and 2 years, with
      peripheral platelet counts averaging 64 +/- 19 x 10(3)/microL (P = .004 compared
      with 228 +/- 92 x 10(3)/microL in 44 normal control animals), mean platelet
      volumes of 11.2 +/- 1.8 fL (P > .5 compared with 10.9 +/- 0. 7 fL in normal
      controls), endogenous thrombopoietin (TPO) levels of 926 +/- 364 pg/mL (P < .001
      compared with 324 +/- 256 pg/mL in normal controls), uniformly elevated platelet
      anti-glycoprotein (GP) IIIa49-66 antibodies, and corresponding viral loads of
      534, 260, and 15 x 10(3) RNA viral copies/mL. Pegylated recombinant human
      megakaryocyte growth and development factor (PEG-rHuMGDF) was administered
      subcutaneously (25 microg/kg twice weekly for 3 doses) to determine the effects
      of stimulating platelet production on peripheral platelet concentrations in this
      cohort of thrombocytopenic HIV-infected chimpanzees. PEG-rHuMGDF therapy
      increased (1) peripheral platelet counts 10-fold (from 64 +/- 19 to 599 +/- 260 x
      10(3) platelets/microL; P = .02); (2) marrow megakaryocyte numbers 30-fold (from
      11.7 +/- 6.5 x 10(6)/kg to 353 +/- 255 x 10(6)/kg; P = .04); (3) marrow
      megakaryocyte progenitor cells fourfold (from a mean of 3.6 +/- 0.6 to 14.1 x
      10(3) CFU-Meg/1, 000 CD34(+) marrow cells); and (4) serum levels of Mpl ligand
      from 926 +/- 364 pg/mL (endogenous TPO) to predosing trough levels of 1, 840 +/-
      353 pg/mL PEG-rHuMGDF (P = .02). The peripheral neutrophil counts were also
      transiently increased from 5.2 +/- 2.6 x 10(3)/microL to 9.9 +/- 5.0 x
      10(3)/microL (P = .01), but neither the erythrocyte counts nor the reticulocyte
      counts were altered significantly (P > .1). The serum levels of antiplatelet
      GPIIIa49-66 antibodies exhibited reciprocal reductions during periods of
      thrombocytosis (P < .07). PEG-rHuMGDF therapy did not increase viral loads
      significantly (395, 189, and 53 x 10(3) RNA viral copies/mL; P > .5 compared with
      baseline values). The striking increase in peripheral platelet counts produced by
      PEG-rHuMGDF therapy implies that thrombocytopenia in HIV-infected chimpanzees is
      attributable to insufficient compensatory expansion in platelet production
      resulting from HIV-impaired delivery of platelets despite stimulated
      megakaryocytopoiesis. These data suggest that PEG-rHuMGDF therapy may similarly
      correct peripheral platelet counts in thrombocytopenic HIV-infected patients.

PMID- 9616136
TI  - Differential chemotactic behavior of developing T cells in response to thymic
      chemokines.
AB  - Differentiation-dependent thymocyte migration in the thymus may be important for
      T lymphopoiesis and might be regulated by thymic chemoattractants. We examined
      modulation of chemotactic responsiveness of thymocyte subsets during their early
      to late stages of development in response to 2 thymus-expressed chemokines, SDF-1
      and CKbeta-11/MIP-3beta/ELC. SDF-1 shows chemotactic preference for immature
      thymocytes (subsets of triple negative thymocytes and double positive [DP]
      subset) over mature single positive (SP) thymocytes. CKbeta-11/MIP-3beta/ELC
      shows low chemotactic activity on the immature thymocytes, but it strongly
      attracts mature SP thymocytes, effects opposite to that of SDF-1. SDF-1-dependent
      chemoattraction of immature thymocytes is not significantly desensitized by a
      negative concentration gradient of CKbeta-11/MIP-3beta/ELC, and chemoattraction
      of mature SP thymocytes to CKbeta-11/MIP-3beta/ELC is not antagonized by SDF-1,
      demonstrating that these two chemokines have different chemoattractant
      preferences for thymocyte subsets and would probably not inhibit each other's
      chemotaxis in the event of microenvironmental coexpression. The chemotactic
      responsiveness of thymocytes and mature T cells to the 2 chemokines is
      respectively enhanced after selection process and migration to the spleen. These
      studies demonstrate the presence of thymocyte chemoattractants with differential
      chemotactic preference for thymocytes, a possible mechanism for thymocyte
      migration in the thymus.

PMID- 9616137
TI  - Interferon-gamma increases expression of chemokine receptors CCR1, CCR3, and
      CCR5, but not CXCR4 in monocytoid U937 cells.
AB  - Chemokine receptors (CR), which can mediate migration of immune cells to the site
      of inflammation, also function as coreceptors for human immunodeficiency virus
      (HIV) entry into CD4+ T lymphocytes and antigen-presenting cells. We demonstrate
      here that interferon-gamma (IFN-gamma) increases the expression of chemokine
      receptors CCR1, CCR3, and CCR5 in monocytoid U937 cells as detected by cell
      surface molecule labeling and mRNA expression, as well as by intracellular
      calcium mobilization and cell migration in response to specific ligands. The
      increased expression of these chemokine receptors also results in an enhanced HIV
      1 entry into cells. Our data provide evidence for a relationship of cellular
      pathways that are induced by IFN-gamma with those that regulate chemokine
      receptor expression.

PMID- 9616138
TI  - Association of germline p53 mutation with MLL segmental jumping translocation in
      treatment-related leukemia.
AB  - Segmental jumping translocations are chromosomal abnormalities in treatment
      related leukemias characterized by multiple copies of the ABL and/or MLL
      oncogenes dispersed throughout the genome and extrachromosomally. Because gene
      amplification potential accompanies loss of wild-type p53, we examined the p53
      gene in a case of treatment-related acute myeloid leukemia (t-AML) with MLL
      segmental jumping translocation. The child was diagnosed with ganglioneuroma and
      embryonal rhabdomyosarcoma (ERMS) at 2 years of age. Therapy for ERMS included
      alkylating agents, DNA topoisomerase I and DNA topoisomerase II inhibitors, and
      local radiation. t-AML was diagnosed at 4 years of age. The complex karyotype of
      the t-AML showed structural and numerical abnormalities. Fluorescence in situ
      hybridization analysis showed multiple copies of the MLL gene, consistent with
      segmental jumping translocation. A genomic region including CD3, MLL, and a
      segment of band 11q24 was unrearranged and amplified by Southern blot analysis.
      There was no family history of a cancer predisposing syndrome, but single-strand
      conformation polymorphism (SSCP) analysis detected identical band shifts in the
      leukemia, ganglioneuroma, ERMS, and normal tissues, consistent with a germline
      p53 mutation, and there was loss of heterozygosity in the ERMS and the t-AML.
      Sequencing showed a CGA-->TGA nonsense mutation at codon 306 in exon 8. The
      results of this analysis indicate that loss of wild-type p53 may be associated
      with genomic instability after DNA-damaging chemotherapy and radiation, manifest
      as a complex karyotype and gene amplification in some cases of t-AML.

PMID- 9616139
TI  - Frequent dysregulation of the c-maf proto-oncogene at 16q23 by translocation to
      an Ig locus in multiple myeloma.
AB  - Dysregulation of oncogenes by translocation to an IgH (14q32) or IgL (kappa, 2p11
      or lambda, 22q11) locus is a frequent event in the pathogenesis of B-cell tumors.
      Translocations involving an IgH locus and a diverse but nonrandom array of
      chromosomal loci occur in most multiple myeloma (MM) tumors even though the
      translocations often are not detected by conventional cytogenetic analysis. In a
      continuing analysis of translocations in 21 MM lines, we show that the novel,
      karyotypically silent t(14;16)(q32.3;q23) translocation is present in 5 MM lines,
      with cloned breakpoints from 4 lines dispersed over an approximately 500-kb
      region centromeric to the c-maf proto-oncogene at 16q23. Another line has a
      t(16;22)(q23;q11), with the breakpoint telomeric to c-maf, so that the
      translocation breakpoints in these 6 lines bracket c-maf. Only these 6 lines
      overexpress c-maf mRNA. As predicted for dysregulation of c-maf by translocation,
      there is selective expression of one c-maf allele in 2 informative lines with
      translocations. This is the first human tumor in which the basic zipper c-maf
      transcription factor is shown to function as an oncogene.

PMID- 9616140
TI  - Positron emission tomography in non-Hodgkin's lymphoma: assessment of
      chemotherapy with fluorodeoxyglucose.
AB  - Positron emission tomography (PET) using F-18 fluorodeoxyglucose (FDG) was
      performed in non-Hodgkin's lymphoma (NHL), which is known to be highly responsive
      to chemotherapy, but also yields variable treatment results to answer the
      following questions: (1) What is the extent and time course of changes in FDG
      utilization in response to chemotherapy? (2) Are the changes of FDG uptake at
      early time points of chemotherapy predictive for therapy outcome? (3) Which
      quantitative FDG parameter provides the most sensitive measures of initial tumor
      response? Dynamic PET scans were performed in 11 patients at baseline and 1 and 6
      weeks after initiation of chemotherapy. Based on attenuation corrected images
      acquired 30 to 60 minutes postinjection, standardized uptake values (SUV) were
      determined. Arterial input functions were estimated from vascular F-18 activity
      and the metabolic rates for FDG (MRFDG) were calculated using Patlak analysis.
      Before chemotherapy, high FDG uptake was found in all lesions (SUV[max] 13.3 +/-
      4.2). Seven days after initiation of chemotherapy, tumor FDG uptake decreased 60%
      (SUV[max]). A further decrease of 42% was seen at day 42 resulting in a total
      decrease of 79% from baseline to day 42. During a follow-up of 16.0 +/- 4.2
      months, six of the 11 patients continued to show complete remission. Seven days
      after initiation of chemotherapy, this group of patients displayed significantly
      lower mean MRFDG than the group of patients with relapse. At day 42, all
      parameters of FDG uptake showed a significant difference for both patient groups.
      The relative change of MRFDG from baseline to day 42, as well as from day 7 to
      day 42, was significantly larger as compared with SUV parameters. Standard
      chemotherapy of patients with NHL causes rapid decrease of tumor FDG uptake as
      early as 7 days after treatment, which continues to decline during therapy,
      indicating the sensitivity of metabolic signals to chemotherapeutic
      interventions. FDG uptake at 42 days after therapy was superior in prediction of
      long-term outcome over day 7 parameters. Dynamic data acquisition combined with
      Patlak analysis of FDG kinetics may provide superior information in therapy
      monitoring.

PMID- 9616141
TI  - Fetal hemoglobin and F-cell responses to long-term hydroxyurea treatment in young
      sickle cell patients. The French Study Group on Sickle Cell Disease.
AB  - We have studied the cellular and molecular responses to long-term hydroxyurea
      (HU) treatment in 29 severely affected young patients with sickle cell disease
      (mean age, 10.9 +/- 4.1 years). Patients received HU at 20 mg/kg/d on 4
      consecutive days per week initially, with a monthly escalated dose avoiding
      marrow-toxicity (mean steady-state dose, 34.2 +/- 4.6 mg/kg/d) for 12 to 36
      months (mean duration, 22 months). The studied parameters were hemoglobin F
      (HbF), F reticulocytes (F retics), F cells, the amount of HbF per F cell (F/F
      cell), polymer tendency at 40% and 70% oxygen saturation, and hemolysis. Initial
      HbF (Fi) was dispersed (from 0.85% to 13.9%). HbF increased in all patients but
      1. HbF at maximal response (Fmax) reached a sustained level varying from a 1.5
      fold to a 16-fold Fi after a variable delay (6 to 24 months). Fmax was not
      related to HU dosage, but triangle upF (Fmax - Fi) was strongly correlated to
      triangle upMCV (MCVmax - MCVi). HbF increase resulted from the increase of both F
      cells and F/F cell. In this rather short series, Fi and Fmax were not
      significantly associated with age, gender, or beta-globin haplotype. Neither Fmax
      nor triangle upF was related to bone marrow reserve, as measured by baseline
      reticulocyte or neutrophil counts. However, Fmax was highly dependent on Fi. When
      patients are individualized into three groups according to Fmax (group 1, Fmax
      >20% [12 patients]; group 2, 10% < Fmax < 20% [11 patients]; group 3, Fmax <10%
      [5 patients]), Fi is significantly different between groups, being the highest in
      group 1. In addition, the best responders (group 1) were significantly different
      from patients in the two other groups with higher levels of total hemoglobin,
      decreased bilirubin, and decreased polymer tendency.

PMID- 9616142
TI  - Pgp and MRP activities using calcein-AM are prognostic factors in adult acute
      myeloid leukemia patients.
AB  - Thirteen cell lines with different levels of Pgp and MRP expression were used to
      assess the ability of calcein acetoxymethyl ester (calcein-AM) uptake and calcein
      efflux to measure Pgp and MRP functions, respectively. There was a good
      correlation between MRP expression and the modulatory effect of probenecid (a
      specific modulator of MRP) on the calcein efflux (r = .91, P = .0003) and between
      Pgp expression and the modulatory effect of CsA on calcein-AM uptake (r = .96, P
      < .0001). In light of the high correlations for both proteins, we tested calcein
      AM uptake and efflux in fresh myeloid leukemic cells. In 53 acute myeloid
      leukemia (AML) patients, there was also a good correlation between MRP expression
      (measured by reverse transcription-polymerase chain reaction and by MRPm6
      expression by flow cytometry) and the modulatory effect of probenecid on the
      calcein fluorescence (r = .92, P < .0001) and between Pgp expression as measured
      by UIC2 antibody binding on flow cytometry and the modulatory effect of
      cyclosporin A on calcein-AM uptake (r = .83, P < .0001). Pgp activity was higher
      in CD34+ leukemia than in CD34- leukemia (2.26 +/- 1.50 v 1.46 +/- 1.21,
      respectively; P = .003), and MRP activity was higher in CD34- leukemia than in
      CD34+ leukemia (1.77 +/- 0.40 v 1.4 +/- 0. 29, respectively; P = .004). Pgp
      expression and activity (P = .004 and P = .01, respectively) and MRP activity (P
      = .03) but not MRP expression were prognostic factors for achievement of complete
      remission. These results suggest that functional testing (with calcein-AM +/-
      modulators) for the presence of both MRP and Pgp activities is of prognostic
      value and that MRP contributes to drug resistance in AML.

PMID- 9616143
TI  - Collection, tumor contamination, and engraftment kinetics of highly purified
      hematopoietic progenitor cells to support high dose therapy in multiple myeloma.
AB  - Unfractionated peripheral blood stem cell (PBSC) grafts contain measurable
      quantities of myeloma cells and are therefore a potential source of relapse
      posttransplantation. In contrast, fluorescence-activated cell sorting (FACS)
      sorted CD34+ Thy1+ Lin- peripheral blood cells are substantially enriched for
      stem cell activity, yet contain virtually no clonal myeloma cells. A study was
      performed in patients with symptomatic myeloma, who had received 12 months or
      less of preceding standard chemotherapy, to evaluate the feasibility of large
      scale purification of primitive hematopoietic stem cells in order to study
      engraftment kinetics posttransplantation and the degree of tumor cell
      contamination of this cell population, based on polymerase chain reaction (PCR)
      analysis for the patient-specific complementarity-determining region III (CDR
      III). PBSC were mobilized with high dose cyclophosphamide and granulocyte
      macrophage colony-stimulating factor (GM-CSF). A combination of elutriation and
      chemical lysis was used to deplete PBSC collections of monocytes, granulocytes,
      erythrocytes, and platelets. Subsequently, CD34+ Thy1+ Lin- progenitor cells were
      purified with high speed cell sorting. Of the 10 evaluable patients, nine met the
      required minimum criteria of >/=7.2 x 10(5) cells/kg to support tandem
      transplants. After high dose melphalan (200 mg/m2) eight engrafted successfully,
      although granulocyte (absolute neutrophil count [ANC] >0.5 x 10(9)/L, 16 days)
      and platelet recovery (platelets > 50 x 10(9)/L, 39 days) was substantially
      delayed when compared with unmanipulated PBSC grafts; one patient required
      infusion of a reserve graft because of lack of evidence of engraftment by day
      +28. Three patients proceeded to a second graft with high dose melphalan and
      total body irradiation; two required infusion of a reserve graft and both died of
      infectious complications; one showed delayed, but complete, engraftment after
      this myeloablative regimen. Two of the nine evaluable patients attained a
      clinical complete remission (CR). The grafts from three patients were tested for
      tumor contamination and contained no detectable clonal myeloma cells. Larger
      quantities of purified cells may be required to resolve the problem of delayed
      engraftment.

PMID- 9616144
TI  - Predictive value of clonality assays in patients with non-Hodgkin's lymphoma
      undergoing autologous bone marrow transplant: a single institution study.
AB  - Recent studies have documented an increased risk of therapy-related
      myelodysplastic syndrome or acute myelogenous leukemia (t-MDS/AML) after
      autologous bone marrow transplant (ABMT) for non-Hodgkin's lymphoma (NHL). To
      develop methods to identify patients at risk for this complication, we have
      investigated the predictive value of clonal bone marrow (BM) hematopoiesis for
      the development of t-MDS/AML, as defined by an X-inactivation based clonality
      assay at the human androgen receptor locus (HUMARA), in a group of patients
      undergoing ABMT for NHL from a single institution (Dana-Farber Cancer Institute,
      Boston, MA). One hundred four female patients were analyzed. At the time of ABMT,
      the prevalence of polyclonal hematopoiesis was 77% (80/104), of skewed X
      inactivation pattern (XIP) was 20% (21/104), and of clonal hematopoiesis was 3%
      (3/104). To determine the predictive value of clonality for the development of t
      MDS/AML, a subgroup of 78 patients with at least 18 months follow-up was
      analyzed. As defined by the HUMARA assay, 53 of 78 patients had persistent
      polyclonal hematopoiesis, 15 of 78 had skewed XIP, and 10 of 78 (13.5%) either
      had clonal hematopoiesis at the time of ABMT or developed clonal hematopoiesis
      after ABMT. t-MDS/AML developed in 2 of 53 patients with polyclonal hematopoiesis
      and in 4 of 10 with clonal hematopoiesis. We conclude that a significant
      proportion of patients have clonal hematopoiesis at the time of ABMT and that
      clonal hematopoiesis, as detected by the HUMARA assay, is predictive of the
      development of t-MDS/AML (P = .004).

PMID- 9616145
TI  - Circulating primitive stem cells in paroxysmal nocturnal hemoglobinuria (PNH) are
      predominantly normal in phenotype but granulocyte colony-stimulating factor
      treatment mobilizes mainly PNH stem cells.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia
      resulting from a somatic mutation in a hemopoietic stem cell. In most cases of
      hemolytic PNH, the majority of the marrow cells are derived from the PNH clone.
      Recent evidence has indicated, however, that the majority of the most primitive
      peripheral blood stem cells (PBSCs) in PNH appear to be of normal phenotype. This
      has led to tentative suggestions that normal PBSCs could be collected and used
      for autologous transplantation. We have investigated this possibility in four PNH
      patients by treating them with granulocyte colony-stimulating factor (G-CSF) in
      an attempt to mobilize normal progenitors. The expression of
      glycosylphosphatidylinositol (GPI)-linked proteins was analyzed by flow cytometry
      on mature neutrophils, late stem cells (CD34+/CD38+), and primitive stem cells
      (CD34+/CD38-). The phenotyping and stem cell quantitation was performed in steady
      state blood and post-G-CSF administration. The most primitive PBSCs (CD34+/CD38-)
      were almost all normal before G-CSF treatment, even when the patients'
      neutrophils were mainly PNH. However, after G-CSF, the cells that were mobilized
      into the peripheral blood were of a similar phenotype to the mature neutrophils,
      ie, mainly PNH. It is possible that PNH-stem cells are preferentially destroyed
      by complement in the peripheral blood leaving only normal cells in the
      circulation. After G-CSF, the PNH cells in the marrow are released into the
      blood. Our findings suggest that it would be difficult to collect sufficient
      numbers of normal stem cells for autologous transplantation.

PMID- 9616146
TI  - A potential molecular approach to ex vivo hematopoietic expansion with
      recombinant epidermal growth factor receptor-expressing adenovirus vector.
AB  - Ex vivo expansion of hematopoietic stem cell (HSC) is an attractive technology
      for its potency of a variety of clinical applications. Such a technology has been
      achieved to some extent with combinations of various cytokines or continuous
      perfusion cultures. However, much more improvement is required especially for
      expansion of primitive hematopoietic progenitors. We propose here a novel
      molecular approach that might have the potential to compensate the current
      expansion. We designed an adenovirus vector to transiently express human
      epidermal growth factor receptor (EGFR), which is known to transduce only a
      mitogenic, but not a differentiation signal to mouse bone marrow cells on human
      purified CD34+ peripheral blood (PB) cells, and tried to expand these cells with
      EGF ex vivo. Because we found that exposure of CD34+ PB cells to cytokines
      induced surface expression of adenovirus-internalization receptor and rendered
      these cells permissive to adenovirus infection, we infected these cells with the
      adenovirus vector carrying EGFR gene in the presence of cytokines. Two-color flow
      cytometric analysis demonstrated that 60.3% +/- 22.4% of CD34+ cells expressed
      the adenovirus-mediated EGFR. Moreover, long-term culture-initiating cell assay
      showed that adenovirus vector could transduce more primitive progenitors.
      Subsequently, we tried to expand these cells in suspension culture with EGF for 5
      days. Methylcellulose clonal assay showed that EGF induced 5.0- +/- 2.4-fold
      proliferation of the colony-forming unit pool during 5 days of expansion. The
      simple procedure of efficient adenovirus gene delivery to immature hematopoietic
      cells proved promising, and this technique was potentially applicable for a novel
      strategy aiming at ex vivo expansion of hematopoietic progenitors.

PMID- 9616147
TI  - Ex vivo culture of CD34+/Lin-/DR- cells in stroma-derived soluble factors,
      interleukin-3, and macrophage inflammatory protein-1alpha maintains not only
      myeloid but also lymphoid progenitors in a novel switch culture assay.
AB  - We have demonstrated that long-term culture initiating cells (LTC-IC) are
      maintained in a stroma noncontact (SNC) culture where progenitors are separated
      from stroma by a microporous membrane and LTC-IC can proliferate if the culture
      is supplemented with interleukin-3 (IL-3) and macrophage inflammatory protein
      1alpha (MIP-1alpha). We hypothesize that the same conditions, which result in LTC
      IC proliferation, may also maintain lymphoid progenitors. Natural killer (NK)
      cells are of lymphoid lineage and a stromal-based culture can induce CD34+/Lin
      /DR- cells to differentiate along the NK cell lineage. We developed a three-step
      switch culture assay that was required to demonstrate the persistence of NK
      progenitors in CD34+/Lin-/DR- cells assayed in SNC cultures supplemented with IL
      3 and MIP-1alpha. When CD34+/Lin-/DR- progeny from the SNC culture were plated
      sequentially into "NK cell progenitor switch" conditions (contact with stromal
      ligands, hydrocortisone-containing long-term culture medium, IL-2, IL-7, and stem
      cell factor [SCF]) followed by "NK cell differentiation" conditions (contact with
      stromal ligands, human serum, no hydrocortisone, and IL-2), significant numbers
      of CD56+/CD3- NK resulted, which exhibited cytotoxic activity against K562
      targets. All steps are required because a switch from SNC cultures with IL-3 and
      MIP-1alpha directly to "NK cell differentiation" conditions failed to yield NK
      cells suggesting that critical step(s) in lymphoid commitment were missing.
      Additional experiments showed that CD34+/CD33- cells present after SNC cultures
      with IL-3 and MIP-1alpha, which contained up to 30% LTC-IC, are capable of NK
      outgrowth using the three-step switch culture. Limiting dilution analysis from
      these experiments showed a cloning frequency within the cultured CD34+/CD33-
      population similar to fresh sorted CD34+/Lin-/DR- cells. However, after addition
      of FLT-3 ligand, the frequency of primitive progenitors able to develop along the
      NK lineage increased 10-fold. In conclusion, culture of primitive adult marrow
      progenitors ex vivo in stroma-derived soluble factors, MIP-1alpha, and IL-3
      maintains both very primitive myeloid (LTC-IC) and lymphoid (NK) progenitors and
      suggests that these conditions may support expansion of human hematopoietic stem
      cells. Addition of FLT-3 ligand to IL-2, IL-7 SCF, and stromal factors are
      important in early stages of NK development.

PMID- 9616148
TI  - The chemokine receptor CXCR-4 is expressed on CD34+ hematopoietic progenitors and
      leukemic cells and mediates transendothelial migration induced by stromal cell
      derived factor-1.
AB  - The chemokine stromal cell-derived factor-1 (SDF-1) and its receptor CXCR-4
      (fusin, LESTR) are likely to be involved in the trafficking of hematopoietic
      progenitor and stem cells, as suggested by the reduced bone marrow hematopoiesis
      in SDF-1-deficient mice and the chemotactic effect of SDF-1 on CD34+ progenitor
      cells. Migration of leukemic cells might also depend on the expression of
      chemokine receptors. Therefore, we analyzed expression of CXCR-4 on mobilized
      normal CD34+ progenitors and leukemic cells. In addition, SDF-1-induced
      transendothelial migration across a bone marrow endothelial cell layer was
      assessed in vitro. By flow cytometry, CXCR-4 was found to be expressed in
      significant amounts on circulating CD34+ hematopoietic progenitor cells,
      including more primitive subsets (CD34+/CD38- and CD34+/Thy-1+ cells). In
      accordance with the immunofluorescence data, CD34+ progenitors efficiently
      migrated across endothelium in response to SDF-1 containing conditioned medium
      from the stromal cell line MS-5. Leukemic blasts (mostly CD34+) from patients
      with acute myeloblastic leukemia (AML) expressed variable amounts of CXCR-4,
      which was functionally active, as demonstrated by a positive correlation between
      the SDF-1-induced transendothelial migration and the cell surface density of CXCR
      4 (r = 0.97). Also recombinant SDF-1beta induced migration of CXCR-4-positive
      leukemic blasts. The effect of both conditioned medium and recombinant SDF-1 was
      inhibited by a CXCR-4 blocking antibody. In contrast, CD34+ leukemic cell lines
      (KG1, KG1a, Kasumi-1, MOLM-1) expressed low levels or were negative for CXCR-4,
      and did not migrate. By reverse transcriptase-polymerase chain reaction (RT-PCR),
      however, basal levels of CXCR-4 mRNA were also detected in all leukemic cell
      lines. We conclude that CXCR-4 is expressed on CD34+ cells including more
      primitive, pluripotent progenitors, and may therefore play a role in the homing
      of hematopoietic stem cells. CXCR-4 expressed in variable amounts on primary AML
      leukemic cells is functionally active and may be involved in the trafficking of
      malignant hematopoietic cells.

PMID- 9616149
TI  - Regulation of p21(WAF1) expression during normal myeloid differentiation.
AB  - The G1-phase cell-cycle inhibitor p21 has been proposed to mediate growth arrest
      during differentiation. Upregulation of p21 has been shown in multiple cell lines
      induced to differentiate; however, the mechanism of p21 induction during normal
      differentiation is largely unknown. In this report, we use normal hematopoietic
      precursor cells obtained from umbilical cord to model p21 regulation during
      differentiation. Myeloid maturation of CD34+ precursor cells is associated with a
      marked increase in p21 expression at the RNA and protein level. The upregulation
      of p21 transcripts during differentiation is associated with decreased binding to
      a highly conserved 44-bp fragment within the p21 promoter. This 44-bp regulatory
      element binds a novel modulator of p21 expression. It is of considerable interest
      that, although the binding activity is expressed in p53-negative as well as in
      p53-positive cells, the DNA sequence recognized by this protein overlaps a
      PuPuPuC(A/T)(T/A)GPyPyPy consensus sequence for p53.

PMID- 9616150
TI  - A new cytokine-dependent monoblastic cell line with t(9;11)(p22;q23)
      differentiates to macrophages with macrophage colony-stimulating factor (M-CSF)
      and to osteoclast-like cells with M-CSF and interleukin-4.
AB  - Monocytes/macrophages exert a series of important functions in vivo. To
      facilitate detailed investigation of their functional capacity and the mechanism
      leading to their differentiation, several cell lines have been established from
      primary material. We present here a new human monoblastic cell line, designated
      UG3. UG3 cells are characterized by the following features. (1) UG3 cells harbor
      the t(9;11)(p22;q23) translocation that results in fusion of the MLL and the AF9
      genes and produce the corresponding AF9-MLL and MLL-AF9 fusion transcripts. (2)
      UG3 cells rely on the presence of exogenous growth factors for viability and
      proliferation, such as interleukin-3 (IL-3), granulocyte-macrophage colony
      stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), or
      macrophage colony-stimulating factor (M-CSF). (3) When cultured in the presence
      of G-CSF, UG3 cells differentiate along the granulocytic lineage, as evidenced by
      segmentation of nuclei and positive staining for neutrophilic alkaline
      phosphatase and peroxidase. (4) When cultured in the presence of GM-CSF or M-CSF,
      UG3 cells differentiate into mature macrophages while preserving surface
      expression of CD14 and CD68 and also start to release cytokines into cell-culture
      supernatants. Under these culture conditions, UG3 cells also take up acetylated
      LDL. (5) When cultured in the presence of M-CSF and IL-4, UG3 cells differentiate
      into osteoclast-like multinucleated giant cells capable of bone resorption and
      display tartrate-resistant acid phosphatase (TRAP) activity. UG3 cells thus
      provide features to qualify them as a useful model to further investigate the
      mechanism underlying these processes and also to further elucidate the functional
      role of mature monocytes/macrophages or osteoclasts.

PMID- 9616151
TI  - A 5' regulatory sequence containing two Ets motifs controls the expression of the
      Wiskott-Aldrich syndrome protein (WASP) gene in human hematopoietic cells.
AB  - The recently-identified Wiskott-Aldrich syndrome protein gene (WASP) is
      responsible for the Wiskott-Aldrich X-linked immunodeficiency as well as for
      isolated X-linked thrombocytopenia (XLT). To characterize the regulatory
      sequences of the WASP gene, we have isolated, sequenced and functionally analyzed
      a 1.6-Kb DNA fragment upstream of the WASP coding sequence. Transfection
      experiments showed that this fragment is capable of directing efficient
      expression of the reporter chloramphenicol acetyltransferase (CAT) gene in all
      human hematopoietic cell lines tested. Progressive 5' deletions showed that the
      minimal sequence required for hematopoietic-specific expression consists of 137
      bp upstream of the transcription start site. This contains potential binding
      sites for several hematopoietic transcription factors and, in particular, two Ets
      1 consensus that proved able to specifically bind to proteins present in nuclear
      extracts of Jurkat cells. Overexpression of Ets-1 in HeLa resulted in
      transactivation of the CAT reporter gene under the control of WASP regulatory
      sequences. Disruption of the Ets-binding sequences by side-directed mutagenesis
      abolished CAT expression in Jurkat cells, indicating that transcription factors
      of the Ets family play a key role in the control of WASP transcription.

PMID- 9616152
TI  - Transgenically produced human antithrombin: structural and functional comparison
      to human plasma-derived antithrombin.
AB  - Recombinant human antithrombin (rhAT) produced in transgenic goat milk was
      purified to greater than 99%. The specific activity of the rhAT was identical to
      human plasma-derived AT (phAT) in an in vitro thrombin inhibition assay. However,
      rhAT had a fourfold higher affinity for heparin than phAT. The rhAT was analyzed
      and compared with phAT by reverse phase high-performance liquid chromatography,
      circular dichroism, fluorophore-assisted carbohydrate electrophoresis (FACE),
      amino acid sequence, and liquid chromatography/mass spectrography peptide
      mapping. Based on these analyses, rhAT was determined to be structurally
      identical to phAT except for differences in glycosylation. Oligomannose
      structures were found on the Asn 155 site of the transgenic protein, whereas only
      complex structures were observed on the plasma protein. RhAT contained a GalNAc
      for galactose substitution on some N-linked oligosaccharides, as well as a high
      degree of fucosylation. RhAT was less sialylated than phAT and contained both N
      acetylneuraminic and N-glycolylneuraminic acid. We postulate that the increase in
      affinity for heparin found with rhAT resulted from the presence of oligomannose
      type structures on the Asn 155 glycosylation site and differences in sialylation.

PMID- 9616153
TI  - Rapid activation of protein C by factor Xa and thrombin in the presence of
      polyanionic compounds.
AB  - A recent study indicated that negatively charged substances such as heparin and
      dextran sulfate accelerate thrombin activation of coagulation factor XI by a
      template mechanism. Because the serine proteinase of the natural anticoagulant
      pathway, activated protein C, can bind heparin, it was reasonable to think that
      these compounds may also bind protein C (PC) and accelerate its activation by
      thrombin or other heparin binding plasma serine proteinases by a similar
      mechanism. To test this, PC activation by thrombin and factor Xa (fXa) was
      studied in the presence of these polysaccharides. With thrombin in the absence of
      thrombomodulin (TM), these polysaccharides markedly reduced the Km for PC and Gla
      domainless PC (GDPC) activation in the presence of Ca2+. With TM containing
      chondroitin sulfate, heparin did not influence PC activation by thrombin, but
      with TM lacking chondroitin sulfate, the characteristic high-affinity PC
      interaction at low Ca2+ (approximately 50 to 100 micromol/L) was largely
      eliminated by heparin. In EDTA, heparin enhanced thrombin activation of GDPC by
      reducing the Km, but it inhibited PC activation by increasing the Km. PC
      activation in EDTA was insensitive to the presence of heparin if the exosite 2
      mutant, R93,97,101A thrombin, was used for activation. These results suggest
      that, when the Gla-domain of PC is not fully stabilized by Ca2+, it interacts
      with the anion binding exosite 2 of thrombin and that heparin binding to this
      site prevents this interaction. Additional studies indicated that, in the
      presence of phospholipid vesicles, heparin and dextran sulfate dramatically
      accelerate PC activation by fXa by also reducing the Km. Interestingly, on
      phospholipids containing 40% phosphatidylethanolamine, the activation rate of
      near physiological PC concentrations ( approximately 80 nmol/L) by fXa in the
      presence of dextran sulfate was nearly comparable to that observed by the
      thrombin-TM complex. The biochemical and potential therapeutical ramifications of
      these findings are discussed.

PMID- 9616154
TI  - Blood coagulation in hemophilia A and hemophilia C.
AB  - Tissue factor (TF)-induced coagulation was compared in contact pathway suppressed
      human blood from normal, factor VIII-deficient, and factor XI-deficient donors.
      The progress of the reaction was analyzed in quenched samples by immunoassay and
      immunoblotting for fibrinopeptide A (FPA), thrombin-antithrombin (TAT), factor V
      activation, and osteonectin. In hemophilia A blood (factor VIII:C <1%) treated
      with 25 pmol/L TF, clotting was significantly delayed versus normal, whereas
      replacement with recombinant factor VIII (1 U/mL) restored the clot time near
      normal values. Fibrinopeptide A release was slower over the course of the
      experiment than in normal blood or hemophilic blood with factor VIII replaced,
      but significant release was observed by the end of the experiment. Factor V
      activation was significantly impaired, with both the heavy and light chains
      presenting more slowly than in the normal or replacement cases. Differences in
      platelet activation (osteonectin release) between normal and factor VIII
      deficient blood were small, with the midpoint of the profiles observed within 1
      minute of each other. Thrombin generation during the propagation phase
      (subsequent to clotting) was greatly impaired in factor VIII deficiency, being
      depressed to less than 1/29 (<1.9 nmol TAT/L/min) the rate in normal blood (55
      nmol TAT/L/min). Replacement with recombinant factor VIII normalized the rate of
      TAT generation. Thus, coagulation in hemophilia A blood at 25 pmol/L TF is
      impaired, with significantly slower thrombin generation than normal during the
      propagation phase; this reduced thrombin appears to affect FPA production and
      factor V activation more profoundly than platelet activation. At the same level
      of TF in factor XI-deficient blood (XI:C <2%), only minor differences in clotting
      or product formation (FPA, osteonectin, and factor Va) were observed. Using
      reduced levels of initiator (5 pmol/L TF), the reaction was more strongly
      influenced by factor XI deficiency. Clot formation was delayed from 11.1 to 15.7
      minutes, which shortened to 9.7 minutes with factor XI replacement. The maximum
      thrombin generation rate observed ( approximately 37 nmol TAT/L/min) was
      approximately one third that for normal (110 nmol/L TAT/min) or with factor XI
      replacement (119 nmol TAT/L/min). FPA release, factor V activation, and release
      of platelet osteonectin were slower in factor XI-deficient blood than in normal
      blood. The data demonstrate that factor XI deficiency results in significantly
      delayed clot formation only at sufficiently low TF concentrations. However, even
      at these low TF concentrations, significant thrombin is generated in the
      propagation phase after formation of the initial clot in hemophilia C blood.

PMID- 9616155
TI  - The structure and function of murine factor V and its inactivation by protein C.
AB  - Factor V (FV) is a central regulator of hemostasis, serving both as a critical
      cofactor for the prothrombinase activity of factor Xa and the target for
      proteolytic inactivation by the anticoagulant, activated protein C (APC). To
      examine the evolutionary conservation of FV procoagulant activity and functional
      inactivation by APC, we cloned and sequenced the coding region of murine FV cDNA
      and generated recombinant wild-type and mutant murine FV proteins. The murine FV
      cDNA encodes a 2,183-amino acid protein. Sequence comparison shows that the A1-A3
      and C1-C2 domains of FV are highly conserved, demonstrating greater than 84%
      sequence identity between murine and human, and 60% overall amino acid identity
      among human, bovine, and murine FV sequences. In contrast, only 35% identity
      among all three species is observed for the poorly conserved B domain. The
      arginines at all thrombin cleavage sites and the R305 and R504 APC cleavage sites
      (corresponding to amino acid residues R306 and R506 in human FV) are invariant in
      all three species. Point mutants were generated to substitute glutamine at R305,
      R504, or both (R305/R504). Wild-type and all three mutant FV recombinant proteins
      show equivalent FV procoagulant activity. Single mutations at R305 or R504 result
      in partial resistance of FV to APC inactivation, whereas recombinant murine FV
      carrying both mutations (R305Q/R504Q) is nearly completely APC resistant. Thus,
      the structure and function of FV and its interaction with APC are highly
      conserved across mammalian species.

PMID- 9616157
TI  - A mutation of the active protein S gene leading to an EGF1-lacking protein in a
      family with qualitative (type II) deficiency.
AB  - The genomic analysis of a 70-year-old man with recurrent deep venous thrombosis
      having a protein S (PS)-deficient phenotype corresponding to both type III and
      type II evidenced two different mutations: a +5 g-->a mutation in the donor
      splice site of intron e (ivs e) and a ser 460 to Pro mutation. The propositus'
      son, who had a type II PS deficiency phenotype, only bore the ivs e +5 g-->a
      mutation. The study of platelet PS mRNA prepared from this subject showed that
      the ivs e, +5 g-->a mutation led to the generation of two abnormal transcripts,
      one lacking exon 5 and the other lacking exons 5 and 6. The presence of an
      additional PS band with a decreased molecular mass on immunoblots performed in
      reducing conditions suggested the presence of truncated PS lacking EGF1 (encoded
      by exon 5). Two monoclonal antibodies (MoAbs) were used to further characterize
      the nonfunctional plasma PS. Comparison of PS levels measured with each of these
      MoAbs and PS levels in conventional assays was consistent with the presence of an
      abnormal inactive protein in the plasma of both patients bearing the ivs e, +5 g-
      >a mutation, suggesting that variant PS lacking EGF1 is secreted but is devoid of
      activated protein C cofactor activity.

PMID- 9616156
TI  - Adeno-associated viral vector-mediated gene transfer of human blood coagulation
      factor IX into mouse liver.
AB  - Recombinant adeno-associated virus vectors (AAV) were prepared in high titer
      (10(12) to 10(13) particles/mL) for the expression of human factor IX after in
      vivo transduction of murine hepatocytes. Injection of AAV-CMV-F.IX (expression
      from the human cytomegalovirus IE enhancer/promoter) into the portal vein of
      adult mice resulted in no detectable human factor IX in plasma, but in mice
      injected intravenously as newborns with the same vector, expression was initially
      55 to 110 ng/mL. The expression in the liver was mostly transient, and plasma
      levels decreased to undetectable levels within 5 weeks. However, long-term
      expression of human F.IX was detected by immunofluorescence staining in 0.25% of
      hepatocytes 8 to 10 months postinjection. The loss of expression was likely
      caused by suppression of the CMV promoter, because polymerase chain reaction data
      showed no substantial loss of vector DNA in mouse liver. A second vector in which
      F.IX expression was controlled by the human EF1alpha promoter was constructed and
      injected into the portal vein of adult C57BL/6 mice at a dose of 6.3 x 10(10)
      particles. This resulted in therapeutic plasma levels (200 to 320 ng/mL) for a
      period of at least 6 months, whereas no human F.IX was detected in plasma of mice
      injected with AAV-CMV-F.IX. Doses of AAV-EF1alpha-F. IX of 2.7 x 10(11) particles
      resulted in plasma levels of 700 to 3, 200 ng/mL. Liver-derived expression of
      human F.IX from the AAV-EF1alpha-F.IX vector was confirmed by immunofluorescence
      staining. We conclude that recombinant AAV can efficiently transduce hepatocytes
      and direct stable expression of an F.IX transgene in mouse liver, but sustained
      expression is critically dependent on the choice of promoter.

PMID- 9616158
TI  - A new strategy for treatment of autoimmune diseases in chimeric resistant MRL/lpr
      mice.
AB  - A new strategy for the treatment of autoimmune diseases in chimeric resistant
      MRL/lpr mice is established. The strategy includes injection of cyclophosphamide
      (CY), fractionated irradiation (5 Gy x 2), bone grafts (to recruit stromal
      cells), and two transplantations of whole bone marrow cells (WBMCs) from
      allogeneic normal C57BL/6 mice (CY/2X/Bone/2BMT). MRL/lpr mice, thus treated,
      survived more than 40 weeks (1 mouse survived for >40 weeks, 7 for >50 weeks, and
      4 for >60 weeks after these treatments). Immunohistological studies showed that
      the mice were completely free from both lymphadenopathy and autoimmune diseases
      such as systemic lupus erythematosis and rheumatoid arthritis. The levels of
      autoantibodies (IgM/IgG rheumatoid factors and IgM/IgG anti-ssDNA antibodies
      [Abs]) in the treated mice decreased to those in the normal mice. In addition,
      successful cooperation among T cells, B cells, and antigen-presenting cells
      (APCs) was observed. Abnormal T cells with immunophenotypes of B220+/Thy
      1+/CD3+/CD4-/CD8- present in untreated MRL/lpr mice disappeared, and the
      hematolymphoid cells of the treated mice were of donor origin. However, the mice
      that had been irradiated with 8.5 Gy and then reconstituted with T-cell-depleted
      BMCs plus bone grafts died within 2 weeks due to the side effect of irradiation.
      The depletion of CD8+ cells (not CD4+ cells) from WBMCs resulted in graft
      failure; 60% of the recipient mice, thus treated, died within 2 weeks, and all
      recipients died by 15 weeks. Furthermore, limiting dilution assays showed that
      approximately more than 0.5% of T cells contained in the BMCs are necessary not
      only for engraftment of BMCs but also for long-term disease-free survival of the
      recipients. In contrast, recipients that had received CD4-depleted BMCs with CY
      plus fractionated irradiation (5Gy x 2) survived for more than 40 weeks without
      showing graft-versus-host reaction (GVHR). This indicates that CD8(+)cells in the
      BMCs are essential for the successful engraftment of the donor-type
      hematolymphoid cells.

PMID- 9616159
TI  - Inhibition of nuclear factor kappaB activation attenuates apoptosis resistance in
      lymphoid cells.
AB  - Death-inducing ligands (DILs) such as tumor necrosis factor alpha (TNFalpha) or
      the cytotoxic drug doxorubicin have been shown to activate a nuclear factor
      kappaB (NFkappaB)-dependent program that may rescue cells from apoptosis
      induction. We demonstrate here that TRAIL (TNF-related apoptosis-inducing
      ligand), a recently identified DIL, also activates NFkappaB in lymphoid cell
      lines in a kinetic similar to TNFalpha. NFkappaB activity is independent from
      FADD, caspases, and apoptosis induction. To study the influence of NFkappaB
      activity on apoptosis mediated by TRAIL, CD95, TNFalpha, or doxorubicin, NFkappaB
      activation was inhibited using the proteasome inhibitor N-acetyl-L-leucinyl-L
      leucinyl-L-norleucinal or transient overexpression of mutant IkappaBalpha.
      Sensitivity for induction of apoptosis was markedly increased by these treatments
      in apoptosis sensitive cell lines. Moreover, both in cell lines and in primary
      leukemia cells that are resistant towards induction of apoptosis by DILs and
      doxorubicin, antagonization of NFkappaB activity partially restored apoptosis
      sensitivity. These data suggest that inhibition of NFkappaB activation may
      provide a molecular approach to increase apoptosis sensitivity in anticancer
      treatment.

PMID- 9616160
TI  - CD43 interacts with moesin and ezrin and regulates its redistribution to the
      uropods of T lymphocytes at the cell-cell contacts.
AB  - Chemokines as well as the signaling through the adhesion molecules intercellular
      adhesion molecule (ICAM)-3 and CD43 are able to induce in T lymphocytes their
      switching from a spherical to a polarized motile morphology, with the formation
      of a uropod at the rear of the cell. We investigated here the role of CD43 in the
      regulation of T-cell polarity, CD43-cytoskeletal interactions, and lymphocyte
      aggregation. Pro-activatory anti-CD43 monoclonal antibody (MoAb) induced
      polarization of T lymphocytes with redistribution of CD43 to the uropod and the
      CCR2 chemokine receptor to the leading edge of the cell. Immunofluorescence
      analysis showed that all three ezrin-radixin-moesin (ERM) actin-binding proteins
      localized in the uropod of both human T lymphoblasts stimulated with anti-CD43
      MoAb and tumor-infiltrating T lymphocytes. Radixin localized at the uropod neck,
      whereas ezrin and moesin colocalized with CD43 in the uropod. Biochemical
      analyses showed that ezrin and moesin coimmunoprecipitated with CD43 in T
      lymphoblasts. Furthermore, in these cells, the CD43-associated moesin increased
      after stimulation through CD43. The interaction of moesin and ezrin with CD43 was
      specifically mediated by the cytoplasmic domain of CD43, as shown by
      precipitation of both ERM proteins with a GST-fusion protein containing the CD43
      cytoplasmic tail. Videomicroscopy analysis of homotypic cell aggregation induced
      through CD43 showed that cellular uropods mediate cell-cell contacts and
      lymphocyte recruitment. Immunofluorescence microscopy performed in parallel
      showed that uropods enriched in CD43 and moesin localized at the cell-cell
      contact areas of cell aggregates. The polarization and homotypic cell aggregation
      induced through CD43 was prevented by butanedione monoxime, indicating the
      involvement of myosin cytoskeleton in these phenomena. Altogether, these data
      indicate that CD43 plays an important regulatory role in remodeling T-cell
      morphology, likely through its interaction with actin-binding proteins ezrin and
      moesin. In addition, the redistribution of CD43 to the uropod region of migrating
      lymphocytes and during the formation of cell aggregates together with the
      enhancing effect of anti-CD43 antibodies on lymphocyte cell recruitment suggest
      that CD43 plays a key role in the regulation of cell-cell interactions during
      lymphocyte traffic.

PMID- 9616162
TI  - The role of tumor necrosis factor alpha in modulating the quantity of peripheral
      blood-derived, cytokine-driven human dendritic cells and its role in enhancing
      the quality of dendritic cell function in presenting soluble antigens to CD4+ T
      cells in vitro.
AB  - Because dendritic cells (DC) are critically involved in both initiating primary
      and boosting secondary host immune responses, attention has focused on the use of
      DC in vaccine strategies to enhance reactivity to tumor-associated antigens. We
      have reported previously the induction of major histocompatibility complex class
      II-specific T-cell responses after stimulation with tumor antigen-pulsed DC in
      vitro. The identification of in vitro conditions that would generate large
      numbers of DC with more potent antigen-presenting cell (APC) capacity would be an
      important step in the further development of clinical cancer vaccine approaches
      in humans. We have focused attention on identifying certain exogenous cytokines
      added to DC cultures that would lead to augmented human DC number and function.
      DC progenitors from peripheral blood mononuclear cells (PBMC) were enriched by
      adherence to plastic, and the adherent cells were then cultured in serum-free
      XVIVO-15 medium (SFM) for 7 days with added granulocyte-macrophage colony
      stimulating factor (GM-CSF) and interleukin-4 (IL-4). At day 7, cultures
      contained cells that displayed the typical phenotypic and morphologic
      characteristics of DC. Importantly, we have found that the further addition of
      tumor necrosis factor alpha (TNFalpha) at day 7 resulted in a twofold higher
      yield of DC compared with non-TNFalpha-containing DC cultures at day 14.
      Moreover, 14-day cultured DC generated in the presence of TNFalpha (when added at
      day 7) demonstrated marked enhancement in their capacity to stimulate a primary
      allogeneic mixed leukocyte reaction (8-fold increase in stimulation index [SI])
      as well as to present soluble tetanus toxoid and candida albicans (10- to 100
      fold increases in SI) to purified CD4+ T cells. These defined conditions allowed
      for significantly fewer DC and lower concentrations of soluble antigen to be used
      for the pulsing of DC to efficiently trigger specific T-cell proliferative
      responses in vitro. When compared with non-TNFalpha-supplemented cultures, these
      DC also displayed an increased surface expression of CD83 as well as the
      costimulatory molecules, CD80 and CD86. Removal of TNFalpha from the DC cultures
      after 2 or 4 days reduced its enhancing effect on DC yield, phenotype, and
      function. Thus, the continuous presence of TNFalpha over a 7-day period was
      necessary to achieve the maximum enhancing effect observed. Collectively, our
      findings point out the importance of exogenous TNFalpha added to cultures of
      cytokine-driven human DC under serum-free conditions, which resulted in an
      enhanced number and function of these APC. On the basis of these results, we plan
      to initiate clinical vaccine trials in patients that use tumor-pulsed DC
      generated under these defined conditions.

PMID- 9616161
TI  - Interferon-gamma-dependent inducible expression of the human interleukin-12 p35
      gene in monocytes initiates from a TATA-containing promoter distinct from the CpG
      rich promoter active in Epstein-Barr virus-transformed lymphoblastoid cells.
AB  - Interleukin-12 (IL-12) production by human monocytes is stringently regulated
      through the inducibility of both subunits, p35 and p40, and expression of p35
      mRNA is the limiting factor for the secretion of the bioactive IL-12 p70
      heterodimer. Optimal induction of p35 mRNA requires priming of the monocytes by
      interferon-gamma (IFN-gamma), followed by brief exposure to lipopolysaccharide or
      other bacterial products. To investigate control of p35 gene expression, we
      isolated genomic clones containing the human p35 gene and determined the 5' end
      of the mRNA expressed in monocytes. We discovered that a unique p35 transcript is
      induced in monocytes that begins downstream of a consensus TATA box that lies
      within the 5' end of the cDNA originally cloned from Epstein-Barr virus (EBV)
      transformed B cells. Analysis of p35 mRNA by Northern blotting showed that the
      message from monocytes is approximately 200 bases shorter than message derived
      from the EBV-transformed B-cell line VDS. The initiation sites downstream from
      the TATA box were confirmed by RNase protection and 5' RACE. The data indicate
      that p35 transcription can initiate from different sites depending on the cell
      type and that the shorter inducible transcript in monocytes is the one that
      accumulates after stimulation. Protein translation of these two forms may result
      in proteins of different sizes with potential implications for the regulation of
      IL-12 secretion and function.

PMID- 9616163
TI  - MLL and CALM are fused to AF10 in morphologically distinct subsets of acute
      leukemia with translocation t(10;11): both rearrangements are associated with a
      poor prognosis.
AB  - The translocation t(10;11)(p13;q14) has been observed in acute lymphoblastic
      leukemia (ALL) as well as acute myeloid leukemia (AML). A recent study showed a
      MLL/AF10 fusion in all cases of AML with t(10;11) and various breakpoints on
      chromosome 11 ranging from q13 to q23. We recently cloned CALM (Clathrin Assembly
      Lymphoid Myeloid leukemia gene), the fusion partner of AF10 at 11q14 in the
      monocytic cell line U937. To further define the role of these genes in acute
      leukemias, 10 cases (9 AML and 1 ALL) with cytogenetically proven t(10;11)(p12
      14;q13-21) and well-characterized morphology, immunophenotype, and clinical
      course were analyzed. Interphase fluorescence in situ hybridization (FISH) was
      performed with 2 YACs flanking the CALM region, a YAC contig of the MLL region,
      and a YAC spanning the AF10 breakpoint. Rearrangement of at least one of these
      genes was detected in all cases with balanced t(10;11). In 4 cases, including 3
      AML with immature morphology (1 AML-M0 and 2 AML-M1) and 1 ALL, the signals of
      the CALM YACS were separated in interphase cells, indicating a translocation
      breakpoint within the CALM region. MLL was rearranged in 3 AML with
      myelomonocytic differentiation (2 AML-M2 and 1 AML-M5), including 1 secondary
      AML. In all 3 cases, a characteristic immunophenotype was identified (CD4+, CD13
      , CD33+, CD65s+). AF-10 was involved in 5 of 6 evaluable cases, including 1 case
      without detectable CALM or MLL rearrangement. In 2 complex translocations, none
      of the three genes was rearranged. All cases had a remarkably poor prognosis,
      with a mean survival of 9.6 +/- 6.6 months. For the 7 AML cases that were
      uniformly treated according to the AMLCG86/92 protocols, disease-free and overall
      survival was significantly worse than for the overall study group (P = .03 and P
      = .01, respectively). We conclude that the t(10;11)(p13;q14) indicates CALM and
      MLL rearrangements in morphologically distinct subsets of acute leukemia and may
      be associated with a poor prognosis.

PMID- 9616164
TI  - Characterization of t(2;5) reciprocal transcripts and genomic breakpoints in
      CD30+ cutaneous lymphoproliferations.
AB  - NPM-ALK chimeric transcripts, encoded by the t(2;5), lead to an aberrant
      expression of ALK by CD30+ systemic lymphomas. To determine if t(2;5) is involved
      in cutaneous lymphoproliferative disorders, we studied 37 CD30+ cutaneous
      lymphoproliferations, 27 mycosis fungoides (MF), and 16 benign inflammatory
      disorders (BID). NPM-ALK transcripts were detected by nested reverse
      transcription-polymerase chain reaction (RT-PCR) in 1 of 11 lymphomatoid
      papulosis (LyP), 7 of 15 CD30+ primary cutaneous T-cell lymphoma (CTCL), 3 of 11
      CD30+ secondary cutaneous lymphoma, 6 of 27 MF, and 1 of 16 BID. However, the
      expression of NPM-ALK transcripts was not associated with ALK1 immunoreactivity
      in MF, LyP, or BID cases. Only 1 CD30+ primary CTCL and 3 CD30+ secondary
      cutaneous lymphoma were ALK1 immunoreactive. The ALK1+ cases were also
      characterized by amplification of tumor-specific genomic breakpoints on
      derivative chromosome 5. These cases, except for 1 secondary cutaneous lymphoma,
      were also characterized by reciprocal breakpoints on derivative chromosome 2,
      leading to the expression of reciprocal ALK-NPM transcripts. Amplification of
      chromosomal breakpoints on both derivative chromosomes could represent an
      alternative to conventional cytogenetics for the diagnosis of t(2;5) and seems to
      be more reliable than the detection of cryptic NPM-ALK transcripts by nested RT
      PCR.

PMID- 9616165
TI  - Homozygous deletions at chromosome 9p21 involving p16 and p15 are associated with
      histologic progression in follicle center lymphoma.
AB  - Low-grade follicle center lymphoma (LGFCL) is characterized genetically by the
      t(14;18) translocation and an indolent clinical course. Histologic progression
      from LGFCL to an aggressive diffuse large B-cell lymphoma (DLCL) occurs in 60% to
      80% of cases, and this transformation is associated with the accumulation of
      secondary genetic alterations. Using 10 polymorphic microsatellite markers
      spanning the chromosome 9p21 region harboring the p15 (p15(INK4B)/MTS-2/CDKN2B)
      and p16 (p16(INK4A)/MTS-1/CDKN2) tumor-suppressor gene loci, we analyzed 11
      matched pairs of LGFCL and their corresponding progressed DLCL biopsies for loss
      of heterozygosity and homozygous deletions at 9p21. A comparative multiplex
      polymerase chain reaction assay was also used for the detection of homozygous
      deletions. Deletions were identified in 8 of the 11 cases studied (73%): 6
      homozygous (54%) and 2 hemizygous (18%). The deletions were identified
      exclusively in the progressed DLCL biopsies. Immunohistochemical studies showed
      an excellent correlation with the results from the genetic analyses. Of the 9
      matched pairs of LGFCL and progressed DLCL with interpretable immunohistochemical
      staining, 9 of 9 (100%) of the LGFCL showed diffuse reactivity for p16. Four of
      the 9 (44%) immunohistochemically evaluable cases of progressed DLCL showed loss
      of or, in 1 case, markedly diminished p16 expression. All 4 of these cases
      correspondingly showed homozygous deletions at 9p21. Five of the 9 progressed
      DLCL cases showed p16 expression and demonstrated retention of one or both 9p21
      alleles by genetic analysis. This is the first longitudinal series examining
      sequential biopsy specimens of low-grade and progressed FCL for genetic loss at
      9p21 encompassing the p16 and p15 loci. The high frequency and exclusive
      occurrence of deletions involving p16 in the progressed DLCLs suggests that
      genetic loss at 9p21 targeting p16 and/or p15 is an important secondary genetic
      event in the histologic progression of FCL.

PMID- 9616166
TI  - Transferrin receptor-dependent and -independent iron transport in gallium
      resistant human lymphoid leukemic cells.
AB  - Recent studies showed that gallium and iron uptake are decreased in gallium
      resistant (R) CCRF-CEM cells; however, the mechanisms involved were not fully
      elucidated. In the present study, we compared the cellular uptake of 59Fe
      transferrin (Tf) and 59Fe-pyridoxal isonicotinoyl hydrazone (PIH) to determine
      whether the decrease in iron uptake by R cells is caused by changes in Tf
      receptor (TfR)-dependent or TfR-independent iron uptake. We found that both 59Fe
      Tf and 59Fe-PIH uptake were decreased in R cells. The uptake of 59Fe-Tf but not
      59Fe-PIH could be blocked by an anti-TfR monoclonal antibody. After 59Fe-Tf
      uptake, R cells released greater amounts of 59Fe than gallium-sensitive (S)
      cells. However, after 59Fe-PIH uptake 59Fe release from S and R cells was
      similar. 125I-Tf exocytosis was greater in R cells. At confluency, S and R cells
      expressed equivalent amounts of TfR; however, at 24 and 48 hours in culture, TfR
      expression was lower in R cells. Our study suggests that the decrease in Tf-Fe
      uptake by R cells is caused by a combination of enhanced iron efflux from cells
      and decreased TfR-mediated iron transport into cells. Furthermore, because TfR
      dependent and -independent iron uptake is decreased in R cells, both uptake
      systems may be controlled at some level by similar regulatory signal(s).

PMID- 9616167
TI  - Prognostic significance of the cell cycle inhibitor p27Kip1 in chronic B-cell
      lymphocytic leukemia.
AB  - B-cell chronic lymphocytic leukemia (B-CLL) is characterized by the accumulation
      of resting lymphocytes. The identification of p27(kip1), a cyclin-dependent
      kinase inhibitor that contributes to cell cycle arrest and represents a link
      between extracellular signals and cell cycle, prompted us to study p27 protein in
      the lymphocytes from 88 patients with B-CLL and 32 patients with other chronic B
      lymphoproliferative disorders. The expression of p27 protein was higher in B-CLL
      samples with variations among them. In B-CLL, p27 levels were independent of
      absolute number of circulating lymphocytes, but strongly correlated with both
      lymphocyte and total tumor mass (TTM) doubling time. High p27 expression was
      associated with a poorer overall prognosis. In vitro, there was an increased
      spontaneous survival of B-CLL cells expressing high p27 levels. Interleukin-4 (IL
      4) upregulated p27 levels in B-CLL cells, while fludarabine decreased p27 levels.
      Thus, our results indicate that p27 may be a valuable kinetic marker in B-CLL by
      providing instantaneous estimation of the disease doubling time. In addition,
      these results suggest that there is a link between p27 expression and the ability
      of CLL cells to undergo apoptosis.

PMID- 9616169
TI  - Follicular lymphomas contain a clonally linked but phenotypically distinct
      neoplastic B-cell population in the interfollicular zone.
AB  - Follicular lymphomas are thought to arise from the follicle center B cells and
      are characterized by follicular structures that recapitulate many features of
      normal secondary lymphoid follicles. The neoplastic B cells of follicular
      lymphoma reside not only in follicles but also in the interfollicular zone in
      which they form a diffuse infiltrate. We have investigated the frequency, extent,
      and biological characteristics of this interfollicular component in 30 cases of
      follicular lymphoma. An interfollicular B-cell infiltrate of variable extent
      (minimal, moderate, or prominent) was present in all cases. Morphologically
      interfollicular neoplastic B cells were small centrocyte-like cells with lower
      grade cytology and lower proliferation fraction compared with the neoplastic
      follicles. The neoplastic phenotype of these cells (CD20+, light chain
      restricted) was confirmed in 18 cases. Clonal identity between the follicular and
      interfollicular components was shown in five cases using microdissection and PCR
      amplification of immunoglobulin heavy chain genes. Analysis of Ig heavy chain
      gene sequences showed identical variants of tumor subclones in both follicular
      and interfollicular compartments, indicating active tumor cell traffic between
      the two. In six cases in which frozen tissue was available, the immunophenotype
      of follicular and interfollicular tumor cells were compared using
      immunohistochemistry. Activation markers such as CD10, CD38, and CD95 and T-cell
      costimulatory molecules CD80 and CD86, which were expressed by neoplastic
      follicles, were either downregulated or absent in the interfollicular component
      in most of the cases. The low-grade cytological features, low proliferation
      fraction, and downregulation of activation markers in the interfollicular
      neoplastic B cells suggests that these are resting cells analogous to memory B
      cells of normal lymphoid tissues. The presence of such a resting tumor cell
      subpopulation in the majority of follicular lymphomas may partly account for the
      remarkable resistance to therapy of this disease.

PMID- 9616168
TI  - Selective ablation of human T-cell lymphotropic virus type 1 p12I reduces viral
      infectivity in vivo.
AB  - Human T-cell lymphotropic virus type 1 (HTLV-1) is the etiologic agent of adult T
      cell leukemia and HTLV-1-associated myelopathy. Novel, yet conserved RNA
      transcripts encoded from open reading frames (ORFs) I and II of the viral pX
      region are expressed both in vitro and in infected individuals. The ORF I mRNA
      encodes the protein p12(I), which has been shown to localize to cellular
      endomembranes, cooperate with bovine papillomavirus E5 in transformation, as well
      as bind to the IL-2 receptor beta and gamma chains and the H+ vacuolar ATPase. It
      is unknown what role p12(I) plays in the viral life cycle. Using an infectious
      molecular clone of HTLV-1 (ACH) and a derivative clone, ACH.p12(I), which fails
      to produce the p12(I) message, we investigated the importance of p12(I) in
      infected primary cells and in a rabbit model of the infection. ACH.p12(I) was
      infectious in vitro as shown by viral passage in culture and no qualitative or
      quantitative differences were noted between ACH and ACH.p12(I) in
      posttransfection viral antigen production. However, in contrast to ACH,
      ACH.p12(I) failed to establish persistent infection in vivo as indicated by
      reduced anti-HTLV-1 antibody responses, failure to demonstrate viral p19 antigen
      production in peripheral blood mononuclear cell (PBMC) cultures, and only
      transient detection of provirus by polymerase chain reaction in PBMC from
      ACH.p12(I)-inoculated rabbits. These results are the first to show the essential
      role of HTLV-1 p12(I) in the establishment of persistent viral infection in vivo
      and suggest potential new targets in antiviral strategies to prevent HTLV-1
      infection.

PMID- 9616170
TI  - Induction of differentiation in acute promyelocytic leukemia cells by 9-cis
      retinoic acid alpha-tocopherol ester (9-cis tretinoin tocoferil).
AB  - Acute promyelocytic leukemia (APL) has a specific genetic rearrangement between
      the retinoic acid receptor (RAR)-alpha gene and the pml nuclear protein gene. All
      trans retinoic acid (ATRA) induces granulocytic differentiation of APL-derived
      cells and is used to treat APL patients. However, ATRA interacts with normal
      cells with RAR throughout the entire body, and when used at high doses or over a
      long duration, it induces several adverse effects. The development of drugs that
      selectively act on APL cells may contribute to increasing the therapeutic
      efficacy of APL treatment as well as elucidating the mechanisms of response to
      ATRA. In this study, 9-cis retinoic acid alpha-tocopherol ester (9CTT) inhibited
      the proliferation of APL-derived NB4 and HT93 cells and induced differentiation
      markers, such as granulocytic maturation, nitroblue tetrazolium reduction, and
      CD11b expression, in these cells. The effects of 9CTT on non-APL cells, including
      HL-60 and U937 cells, were much weaker than those on APL cells, and tretinoin
      tocoferil (TT), which is an alpha-tocopherol ester of ATRA, did not induce the
      differentiation of APL cells as effectively as 9CTT. The differentiation-inducing
      effects of 9CTT were inhibited by RAR antagonists. 9CTT and TT similarly induced
      the transactivating activity of RARs, but were not effective on RXRs. 9CTT
      downregulated the expression of PML/RAR-alpha protein more effectively than TT,
      which suggests that it may be involved in the selectivity of 9CTT against APL
      cells. Interestingly, 9CTT enhanced the differentiation of APL cells induced by
      ATRA, 9-cis retinoic acid, and synthetic retinobenzoic acids. Combined with
      1alpha,25-dihydroxyvitamin D3 (VD3), 9CTT also more than additively induced the
      differentiation of APL cells. Thus, 9CTT, alone or in combination with other
      retinoids or VD3, may be useful for the treatment of APL.

PMID- 9616171
TI  - A gp130 interleukin-6 transducer-dependent SCID model of human multiple myeloma.
AB  - Agonist antihuman gp130 transducer monoclonal antibodies (MoAbs) were used in
      SCID mice to grow myeloma cells whose survival and proliferation is dependent on
      gp130 transducer activation. The agonist anti-gp130 MoAbs neither bound to murine
      gp130 nor activated murine cells and, as a consequence, did not induce
      interleukin-6 (IL-6)-related toxicities in mice. They have a 2-week half-life in
      vivo when injected in the peritoneum. The agonist antibodies made possible the in
      vivo growth of exogenous IL-6-dependent human myeloma cells as well as that of
      freshly explanted myeloma cells from 1 patient with secondary plasma cell
      leukemia. Tumors occurred 4 to 10 weeks after myeloma cell graft and weighed 3 to
      5 g. They grew as solid tumors in the peritoneal cavity and metastasized to the
      different peritoneal organs: liver, pancreas, spleen, and intestine. Tumoral
      cells were detected in blood and bone marrow of mice grafted with the XG-2
      myeloma cells. Tumoral cells grown in SCID mice had kept the phenotypic
      characteristics of the original tumoral cells and their in vitro growth required
      the presence of IL-6 or agonist anti-gp130 MoAbs. Myeloma cells from 4 patients
      with medullary involvement persisted for more than 1 year as judged by detectable
      circulating human Ig. However, no tumors were detected, suggesting a long-term
      survival of human myeloma cells without major proliferation. These observations
      paralleled those made in in vitro cultures as well as the tumor growth pattern in
      these patients. This gp130 transducer-dependent SCID model of multiple myeloma
      should be useful to study various therapeutical approaches in multiple myeloma in
      vivo.

PMID- 9616172
TI  - Improving the intracellular delivery and molecular efficacy of antisense
      oligonucleotides in chronic myeloid leukemia cells: a comparison of streptolysin
      O permeabilization, electroporation, and lipophilic conjugation.
AB  - The hybrid gene BCR-ABL that typifies chronic myeloid leukemia (CML) represents
      an attractive target for therapy with antisense oligodeoxyribonucleotides (ODN).
      A central obstacle in the therapeutic application of ODN is their poor cellular
      uptake. Adding various lipophilic conjugates to the ODN backbone has been
      reported to improve uptake, and electroporation of target cells has also been
      shown to enhance intracellular ODN delivery. We have shown that (1) BCR-ABL
      directed ODN will specifically decrease the level of BCR-ABL mRNA, provided that
      cells are first permeabilized with Streptolysin-O (SL-O), and (2) chimeric
      methylphosphonodiester:phosphodiester ODN directed against 9 bases either side of
      the BCR-ABL junction are more efficient ODN effectors than structures composed
      solely of phosphodiester or phosphorothioate linkages. In this study, we compared
      the efficacy of lipophilic conjugation, SL-O permeabilization and electroporation
      on the intracellular delivery and molecular effect of BCR-ABL-directed ODN. b2a2-
      and b3a2-directed chimeric ODN were synthesized either unmodified or with one of
      the following groups at the 5' end: cholesterol, vitamin E, polyethylene glycol
      of average molecular weight 2,000 or 5,000, N-octyl-oligo-oxyethylene, or
      dodecanol. ODN associated with Lipofectin was also studied. Comparison was made
      in untreated, electroporated, and SL-O permeabilized KYO1 cells. Uptake was
      examined by fluorescence microscopy and flow cytometry, using ODN structures that
      were 3' labeled with fluorescein. The effect on target BCR-ABL mRNA expression
      was analyzed by Northern blotting. Several conjugated structures associated
      avidly with the cell membrane without achieving significant intracellular uptake
      or molecular effect. Similarly, ODN:Lipofectin complexes moderately increased
      cell association, without enhancing intracellular levels of ODN or inducing
      detectable molecular effect. In SL-O permeabilized or electroporated cells,
      uptake was approximately 1 to 2 logs greater than in untreated cells, and rapid
      nuclear localization was seen, especially with unmodified chimeric ODN. In SL-O
      permeabilized cells treated with ODN directed to the b2a2 and b3a2 junctions
      respectively, b2a2 BCR-ABL mRNA levels at 4 hours were reduced to 2. 6% +/- 2.1%
      and 38.4% +/- 1.3% of control values. In cells permeabilized by electroporation,
      BCR-ABL mRNA levels were decreased to 4.0% +/- 1.4% of control levels by b2a2
      directed ODN, although very little nontargeted suppression was seen with b3a2
      targeted ODN (93.4% +/- 4.2% of control). Greater cell to cell variation in ODN
      uptake was seen for SL-O permeabilized cells when compared with electroporated
      cells, suggesting that, after SL-O permeabilization, relatively unpermeabilized
      and overpermeabilized populations may coexist. No structure had any effect on the
      level of irrelevant (p53, MYC, and GADPH) mRNA levels. We conclude that the
      conjugation of chimeric ODN with one of the above-mentioned lipophilic groups or
      the complexing of ODN with Liopfectin does not improve either intracellular
      delivery of ODN or the molecular effect. In contrast, both electroporation and SL
      O permeabilization (1) considerably enhanced uptake of chimeric ODN (even for
      structures without a conjugate group) and (2) achieved significant suppression of
      target mRNA levels.

PMID- 9616173
TI  - Parathyroid hormone-related protein-induced hypercalcemia in SCID mice engrafted
      with adult T-cell leukemia cells.
AB  - Parathyroid hormone-related protein (PTHrP) is considered to be one of the main
      causes of hypercalcemia associated with adult T-cell leukemia (ATL). To clarify
      the role of PTHrP and bone remodeling in the development of hypercalcemia in ATL,
      we examined the SCID mouse model of ATL that has previously been shown to mimic
      the disease in humans. Using this model, we found clear elevations in serum
      levels of calcium and C-terminal PTHrP (C-PTHrP). PTHrP mRNA was highly expressed
      in ATL cells proliferating in vivo. After the development of hypercalcemia, ATL
      mice were killed and bone histomorphometric analysis was performed. Bone volume
      was clearly decreased in the ATL mice. In comparison to control SCID mice, bone
      formation indices were very low in the ATL mice. Surprisingly, no significant
      difference was detected between the ATL mice and the control SCID mice in eroded
      surface/bone surface (ES/BS), a parameter of bone resorption. To our knowledge,
      the model presented here is the first animal model of ATL with humoral
      hypercalcemia. This is in contrast to previously reported, well-characterized
      animal models of human solid tumors associated with humoral hypercalcemia of
      malignancy (HHM). Furthermore, this model not only provides us with the
      opportunity to study the mechanisms underlying development of elevated calcium
      levels in ATL, but also allows us to test new therapeutic agents designed to
      treat hypercalcemia.

PMID- 9616174
TI  - Individual cell analysis of the cytokine repertoire in human immunodeficiency
      virus-1-infected monocytes/macrophages by a combination of immunocytochemistry
      and in situ hybridization.
AB  - The expression of many cytokines is dysregulated in individuals infected with the
      human immunodeficiency virus-1 (HIV-1). To determine the effects of HIV-1
      infection on cytokine expression in individual cells (at the single cell level),
      we investigated the intracellular levels of proinflammatory cytokines (tumor
      necrosis factor [TNF]-alpha, interleukin [IL]-1beta, IL-6, and IL-8) and
      hematopoietic growth factors (granulocyte colony-stimulating factor [G-CSF],
      granulocyte-macrophage colony-stimulating factor [GM-CSF]) in monocyte-derived
      macrophages, mock-infected, or infected with HIV-1 by immunocytochemical staining
      for cytokine protein and compared this with secreted cytokine levels as
      determined by specific enzyme-linked immunosorbent assay (ELISA). No difference
      in the frequency or intensity of cell-associated immunocytochemical cytokine
      staining could be observed between HIV-1 and mock-infected cells even though the
      level of secreted proinflammatory cytokines increased and the hematopoietic
      growth factors decreased in HIV-1-infected cultures. Furthermore, equal
      expression of cytokine mRNA was observed in all cells in the culture regardless
      of whether the cells were productively infected with HIV-1 as determined by
      double-labelling immunocytochemical staining for HIV-1 p24 antigen and in situ
      hybridization for cytokine mRNA expression. These results indicate that HIV-1
      infection results in dysregulation of intracellular cytokine mRNA expression and
      cytokine secretion not only in HIV-1-infected cells, but also through an indirect
      way(s) affecting cells not producing virus.

PMID- 9616175
TI  - Activation of a plasma membrane-associated neutral sphingomyelinase and
      concomitant ceramide accumulation during IgG-dependent phagocytosis in human
      polymorphonuclear leukocytes.
AB  - The sphingomyelin cycle, which plays an important role in regulation of cell
      growth, differentiation, and apoptosis, involves the formation of ceramide by the
      action of a membrane-associated, Mg2+-dependent, neutral sphingomyelinase and/or
      a lysosomal acid sphingomyelinase. In human polymorphonuclear leukocytes (PMNs),
      ceramide production correlates with and plays a role in the regulation of
      functional responses such as oxidant release and Fcgamma receptor-mediated
      phagocytosis. To increase our understanding of the sphingomyelin cycle in human
      PMNs, the cellular location of neutral and acid sphingomyelinases was
      investigated in resting, formylmethionylleucylphenylalanine (FMLP)-activated, and
      FMLP-activated PMNs engaged in phagocytosis. In resting PMNs, a Mg2+-dependent,
      neutral sphingomyelinase was the predominant activity and was localized to the
      plasma membrane fractions along with the majority of ceramide. Upon FMLP
      activation, there was a 1. 9-fold increase in this neutral, Mg2+-dependent
      sphingomyelinase activity, which increased to 2.7-fold subsequent to phagocytosis
      of IgG opsonized targets. This increase in sphingomyelinase activity was
      restricted to the plasma membrane fractions, which were also the site of
      increased ceramide levels. Phospholipase D (PLD) activity, which is a target of
      ceramide action and is required for phagocytosis, was also found primarily in the
      plasma membrane fractions of FMLP-activated and phagocytosing PMNs. Our findings
      indicate that in human PMNs engaged in phagocytosis, the sphingomyelin cycle is
      restricted to the plasma membrane where intracellular targets of ceramide action,
      such as PLD, are localized.

PMID- 9616176
TI  - The bactericidal/permeability-increasing protein (BPI) is present in specific
      granules of human eosinophils.
AB  - Eosinophils participate in the inflammatory response seen in allergy and
      parasitic infestation, but a role in host defense against bacterial infection is
      not settled. The bactericidal/permeability-increasing protein (BPI) has been
      demonstrated in neutrophils and it exerts bacteriostatic and bactericidal effects
      against a wide variety of Gram-negative bacterial species. Using the Western blot
      technique, a 55-kD band, corresponding to BPI, was detected in lysates from both
      neutrophils and eosinophils. The localization of BPI in immature and mature
      eosinophils was investigated using immunoelectron microscopy. BPI was found in
      immature and mature specific granules of eosinophils and was detected in
      phagosomes as well, indicating release of the protein from the granules into the
      phagosomes. Using a specific enzyme-linked immunosorbent assay, eosinophils were
      shown to contain 179 ng of BPI/5 x 10(6) eosinophils compared with 710 ng BPI/5 x
      10(6) neutrophils. The presence of BPI in eosinophils suggests a role for these
      cells in host defense against Gram-negative bacterial invasion or may suggest a
      role for BPI against parasitic infestation.

PMID- 9616177
TI  - P-Selectin support of neonatal neutrophil adherence under flow: contribution of L
      selectin, LFA-1, and ligand(s) for P-selectin.
AB  - To further define the neonatal neutrophil's ability to localize to inflamed
      tissue compared with adult cells, we examined the neonatal neutrophil
      interactions with P-selectin monolayers under two conditions: (1) attachment
      under constant shear stress and flow and (2) detachment where cells were allowed
      to attach in the absence of shear stress and then shear stress is introduced and
      increased in step-wise increments. Cord blood and adult neutrophils had minimal
      interactions with unstimulated human umbilical vein endothelial cells (HUVECs) at
      a constant shear stress of 2 dynes/cm2. There was a marked increase in the number
      of both neonatal and adult cells interacting (interacting cells = rolling +
      arresting) with HUVECs after histamine stimulation, although the neonatal value
      was only 40% of adult (P < .05). Neonatal neutrophils also had significantly
      decreased interaction with monolayers of Chinese hamster ovary (CHO) cells
      transfected with human P-selectin (CHO-P-selectin; 60% of adult values, P <
      .003). Of the interacting cells, there was a lower fraction of neonatal cells
      that rolled compared with adult cells on both stimulated HUVECs and CHO-P
      selectin. That neonatal neutrophil L-selectin contributes to the diminished
      attachment to P-selectin is supported by the following: (1) Neonatal neutrophils
      had significantly diminished expression of L-selectin. (2) Anti-L-selectin
      monoclonal antibody reduced the number of interacting adult neutrophils to the
      level seen with untreated neonatal neutrophils, but had no effect on neonatal
      neutrophils. In contrast, L-selectin appeared to play no role in maintaining the
      interaction of either neonatal or adult neutrophils in the detachment assay. Once
      attachment occurred, the neonatal neutrophil's interaction with the P-selectin
      monolayer was dependent on LFA-1 and to other ligands to a lesser degree based on
      the following: (1) Control neonatal neutrophils had decreased rolling fraction
      compared with adult neutrophils, although the total number of interacting
      neutrophils was equal between groups. (2) Anti-LFA-1 treatment resulted in an
      increase in the rolling fraction of both neonatal and adult neutrophils. However,
      whereas the number of interacting adult neutrophils remained unchanged, the
      number of neonatal neutrophils decreased with increased shear stress. We
      speculate that this increased detachment of neonatal cells is due to differences
      in neutrophil ligand(s) for P-selectin.

PMID- 9616178
TI  - Lymphocyte-specific protein 1 expression in eukaryotic cells reproduces the
      morphologic and motile abnormality of NAD 47/89 neutrophils.
AB  - Despite its name, the actin-binding protein lymphocyte-specific protein1 (LSP1)
      is found in all hematopoetic cells, and yet its role in cell function remains
      unclear. Recently, LSP1 was identified as the 47-kD protein overexpressed in the
      polymorphonuclear neutrophils of patients with a rare neutrophil disorder,
      neutrophil actin dysfunction with abnormalities of 47-kD and 89-kD proteins (NAD
      47/89). These neutrophils are immotile, defective in actin polymerization in
      response to agonists, and display distinctive, fine, "hairlike" F-actin-rich
      projections on their cell surfaces. We now show that overexpression of LSP1
      produces F-actin bundles that are likely responsible for the morphologic and
      motile abnormalities characteristic of the NAD 47/89 phenotype. Coincident with
      LSP1 overexpression, cells from each of several different eukaryotic lines,
      including a highly motile human melanoma line, develop hairlike surface
      projections that branch distinctively and contain F-actin and LSP1. The hairlike
      projections are supported at their core by thick actin bundles, composed of actin
      filaments of mixed polarity, which periodically anastomose to generate a
      branching structure. The motility of the melanoma cells is inhibited even at low
      levels of LSP1 expression. Therefore, these studies show that overexpression of
      LSP1 alone can recreate the morphologic and motile defects seen in NAD 47/89 and
      suggest that LSP1 is distinct from other known actin binding proteins in its
      effect on F-actin network structure.

PMID- 9616179
TI  - Retinoic acid inhibits monocyte to macrophage survival and differentiation.
AB  - Vitamin A metabolites are potent differentiation-inducing agents for
      myelomonocytic cell lines in vitro and are successfully used for the treatment of
      patients with acute promyelocytic leukemia. However, little is known about the
      effects of vitamin A on normal hematopoietic cells. Therefore, we investigated
      the effect of vitamin A on differentiation and activation of human blood
      monocytes (MO). Culturing MO for up to 4 days with 9-cis retinoic acid (RA) and
      all-trans RA but not retinol reduced MO survival, with the remaining cells being
      morphologically comparable to control cells. Because macrophage colony
      stimulating factor (M-CSF) is a well-known survival factor for MO, we measured
      the M-CSF content of MO culture supernatants using enzyme-linked immunosorbent
      assay and found that RA suppressed the constitutive secretion of M-CSF. Northern
      analysis showed that the M-CSF mRNA expression was only slightly reduced by RA
      treatment, suggesting regulation on the posttranscriptional level. In contrast to
      MO, M-CSF secretion by MO-derived macrophages (MAC) was not altered by RA,
      suggesting a differentiation-dependent switch in the responsiveness of MO/MAC to
      RA. Because M-CSF is not only a survival-promoting but also a differentiation
      promoting factor for myeloid cells, we analyzed the effect of RA on MO to MAC
      maturation. RA suppressed the expression of the maturation-associated antigen
      carboxypeptidase M (CPM)/MAX.1 at both the protein and mRNA levels and modulated
      the lipopolysaccharide-stimulated cytokine secretion of MO/MAC. The addition of
      exogenous M-CSF to RA-containing MO cultures fails to overcome the RA-induced
      inhibition of MO differentiation. However, the survival rate was improved by
      exogenous M-CSF. We conclude that RA acts via two different mechanisms on
      monocyte survival and differentiation: posttranscriptionally by controlling M-CSF
      secretion, which decreases MO survival, and transcriptionally regulating the
      expression of differentiation-associated genes. The regulation of M-CSF
      production may contribute to the antileukemic effect of RA in vivo by reducing
      autocrine M-CSF production by leukemic cells.

PMID- 9616180
TI  - Characterization of Plasmodium falciparum-infected erythrocyte and P-selectin
      interaction under flow conditions.
AB  - Plasmodium falciparum-infected erythrocytes (IRBC) roll on the adhesion molecule
      P-selectin in vitro under flow conditions that approximate the shear stress in
      capillary and postcapillary venules in which cytoadherence occurs in vivo. The
      pathological significance of this adhesive interaction is currently unknown. In
      this study, we further investigated the molecular interactions between IRBC and P
      selectin by using a laminar flow system that allowed for the direct visualization
      of IRBC-substratum interactions. The results showed that the IRBC-P-selectin
      interaction was Ca2+-dependent and involved the lectin domain of P-selectin and a
      sialic acid residue on IRBC. The sialylated P-selectin ligand was trypsin
      sensitive, which suggests that it could be part of the parasite antigen PfEMP1
      that interacts with CD36 and intercellular adhesion molecule-1 (ICAM-1), but
      different from a trypsin-resistant IRBC ligand that adheres selectively to
      chondroitin sulfate A. Studies on the rolling and adhesion of IRBC on activated
      platelets that express both CD36 and P-selectin showed that inhibition of rolling
      on P-selectin reduced the adhesion of some clinical parasite isolates to CD36,
      whereas other parasite isolates appeared to interact directly with CD36. Thus,
      cytoadherence under physiological flow conditions may be mediated by multiple
      IRBC ligands that interact with different adhesion molecules in a cooperative
      fashion. These findings underscore the complexity of the interactions betweeen
      IRBC and vascular endothelium.

PMID- 9616181
TI  - Autologous or allogeneic stem cell transplantation in advanced low-grade
      lymphomas?

PMID- 9616182
TI  - Secondary leukemia responsive to retinoic acid with abnormal localization of
      RARalpha protein: a report of two cases.

PMID- 9616183
TI  - Increased frequency of Fanconi anemia group C genetic variants in children with
      sporadic acute myeloid leukemia.

PMID- 9616184
TI  - Glucuronidation of amines and other xenobiotics catalyzed by expressed human UDP
      glucuronosyltransferase 1A3.
AB  - Glucuronide conjugation of xenobiotics containing a tertiary amine moiety
      represents a unique and important metabolic pathway for these compounds in
      humans. Previously, human UDP-glucuronosyltransferase (UGT) 1A4 was shown to be
      an important enzyme for the formation of quaternary ammonium-linked glucuronides.
      UGT1A3 is 93% identical to UGT1A4 in primary amino acid sequence. We show that
      human UGT1A3, transiently expressed in human embryonic kidney 293 cells, also
      catalyzes the N-glucuronidation of primary, secondary, and tertiary amine
      substrates, such as 4-aminobiphenyl, diphenylamine, and cyproheptadine. In
      contrast to expressed human UGT1A4, which catalyzes the glucuronidation of amines
      with high efficiency, glucuronidation of amines catalyzed by UGT1A3 exhibited low
      efficiency, suggesting that UGT1A3 makes only a limited contribution to the
      metabolic elimination of these compounds. The reactivity of expressed human
      UGT1A3 toward hydroxylated and carboxylic acid-containing compounds was also
      examined. In addition to amines, expressed human UGT1A3 catalyzed the
      glucuronidation of opioids (e.g. morphine and buprenorphine), coumarins,
      flavonoids (e.g. naringenin and quercetin), anthraquinones, and small phenolic
      compounds (e.g. 4-nitrophenol). Drugs containing a carboxylic acid moiety, such
      as nonsteroidal anti-inflammatory agents (e.g. naproxen and ibuprofen) and
      fibrates (e.g. ciprofibrate), were substrates for human UGT1A3. In contrast,
      compounds containing an aliphatic hydroxyl group, such as sapogenins,
      monoterpenoid alcohols (e.g. menthol and borneol), and androgens, were not
      conjugated by expressed human UGT1A3. Of the compounds tested, scopoletin,
      naringenin, and norbuprenorphine appeared to be the best xenobiotic substrates
      for human UGT1A3.

PMID- 9616185
TI  - The in vitro metabolism of penclomedine in mouse, rat, and human systems.
AB  - Penclomedine is a multi-chlorinated alpha-picoline derivative that has
      demonstrated activity in several murine breast cancer models and is currently in
      clinical testing for use against solid tumors. This study evaluates the
      metabolism of penclomedine in several in vitro hepatic models, including
      microsomes, fresh liver slices, and the isolated perfused rat liver (IPRL). Both
      human and mouse liver slices as well as human and mouse liver microsomes under
      aerobic conditions resulted in limited metabolism of penclomedine to several
      oxidized metabolites, including penclomic acid, 4-demethylpenclomic acid, and 4
      demethylpenclomedine. Microsomes under anaerobic conditions vigorously produced
      mainly reduced metabolites, primarily penclomedine dimers. This is in contrast to
      in vivo data, which showed rapid metabolism of penclomedine to primarily 4
      demethylpenclomedine. The IPRL preparation, however, metabolized 50 microM
      penclomedine 90% within 90 min, producing primarily 4-demethylpenclomedine and
      penclomic acid. These were formed in roughly equimolar amounts and did not
      undergo significant further metabolism over 4 hr. Numerous highly polar biliary
      metabolites were also found. The IPRL preparation thus seems to most accurately
      reflect the in vivo situation.

PMID- 9616186
TI  - In vitro and in vivo evaluations of intestinal barriers for the zwitterion L
      767,679 and its carboxyl ester prodrug L-775,318. Roles of efflux and metabolism.
AB  - The barriers to oral delivery of the hydrophilic zwitterion L-767, 679 (I) and
      its carboxyl ester prodrug L-775,318 (II) were examined. In the Caco-2 cell
      model, transport of II, but not I, was strongly oriented in the secretory
      direction. The basal-to-apical transport of II displayed saturable kinetics and
      was markedly inhibited by verapamil and quinidine, known P-glycoprotein
      inhibitors. In Caco-2 cells, metabolism of I was not observed, whereas hydrolysis
      of II was modest (</=20%). In the in situ rat intestinal loop model, verapamil
      did not affect the absorption of I but significantly increased the absorption of
      II. I was resistant to intestinal metabolism, whereas II underwent hydrolysis
      partially in rat lumen but more extensively in rat intestinal tissue and blood.
      In vitro metabolism studies indicated that verapamil also inhibited the
      hydrolysis of II in rats. The inhibition was relatively specific for the
      intestinal and not the luminal esterases. These results suggested that the
      intestinal absorption of I was limited not by intestinal efflux or metabolism but
      more likely by the low lipophilicity of I. However, an efflux system, likely
      mediated by P-glycoprotein, played an important role in limiting the absorption
      of II. In rats, metabolism served as an additional barrier to the absorption of
      II. Verapamil increased the intestinal absorption of the prodrug by inhibiting
      the efflux system in the two models studied, as well as possibly inhibiting
      metabolism in rats. For the first time, secretory transport was identified as a
      cause of the failure to increase the absorption of a lipophilic and cationic
      prodrug developed to overcome the absorption problem.

PMID- 9616187
TI  - Biotransformation of tolterodine, a new muscarinic receptor antagonist, in mice,
      rats, and dogs.
AB  - Tolterodine is a new muscarinic receptor antagonist intended for the treatment of
      urinary urge incontinence and other symptoms associated with an overactive
      bladder. The in vivo metabolism of 14C-labeled tolterodine was investigated in
      rats, mice, and dogs by analysis of blood and urine samples, whereas in vitro
      metabolism studies were performed by incubation of [14C]tolterodine with mouse,
      rat, dog, and human liver microsomes in the presence of NADPH. Tolterodine was
      extensively metabolized in vivo. Mice and dogs showed similar metabolite
      patterns, which correlated well with that observed in humans. In these species,
      tolterodine was metabolized along two different pathways, with the more important
      being the stepwise oxidation of the 5-methyl group to yield the 5-hydroxymethyl
      metabolite of tolterodine and then, via the aldehyde, the 5-carboxylic acid
      metabolite. The other pathway involved dealkylation of the nitrogen. In the
      subsequent phase II metabolism, tolterodine and the metabolites were conjugated
      with glucuronic acid to various degrees. Rats exhibited more extensive metabolism
      and a markedly different metabolite pattern, with metabolites also being formed
      by hydroxylation of the unsubstituted benzene ring. In addition, a gender
      difference was observed, with male rats showing more extensive metabolism than
      females. Incubation of [14C]tolterodine with liver microsomes yielded a total of
      five metabolites with rat liver microsomes and three with mouse, dog, and human
      liver microsomes. The 5-hydroxymethyl metabolite of tolterodine and N-dealkylated
      tolterodine were major metabolites in all incubations, representing 83-99% of
      total metabolism. Although the extent of metabolism varied among species, the
      metabolic profiles were similar. However, rat liver microsomes also formed
      metabolites hydroxylated in the unsubstituted benzene ring. These results show
      that the metabolism of tolterodine in mice and dogs corresponds to that observed
      in humans, whereas rats exhibit a different metabolite pattern.

PMID- 9616188
TI  - In vitro characterization of cytochrome P450 2D6 inhibition by classic histamine
      H1 receptor antagonists.
AB  - Classic antihistamines, namely diphenhydramine, chlorpheniramine, clemastine,
      perphenazine, hydroxyzine, and tripelennamine, share structural features with
      substrates and inhibitors of the polymorphic cytochrome P450 (CYP) isozyme
      CYP2D6. Therefore, the current study was undertaken to characterize the in vitro
      inhibition of CYP2D6 by these commonly used, histamine H1 receptor antagonists.
      Microsomal incubations were performed using bufuralol as a specific CYP2D6
      substrate and microsomes derived from human cells transfected with CYP2D6 cDNA.
      Reaction velocities were assessed in the absence and presence of antihistamines
      (20 microM) at 11 substrate concentrations (1, 2.5, 5, 7.5, 10, 15, 20, 25, 50,
      75, and 100 microM), as well as at three nonsaturating substrate concentrations
      (2.5, 5, and 20 microM) and three inhibitor concentrations (5, 20, and 50
      microM). In the presence of all antihistamines, the Vmax and KM of bufuralol 1'
      hydroxylation were significantly altered, compared with the uninhibited reaction
      (p < 0.05). Lineweaver-Burke plots suggested competitive inhibition of the
      reaction by diphenhydramine and mixed inhibition by all other antihistamines
      tested. Diphenhydramine and chlorpheniramine, with estimated Ki values of
      approximately 11 microM, were the weakest inhibitors of CYP2D6 in vitro. Whereas
      tripelennamine, promethazine, and hydroxyzine were similar in their inhibitory
      capacities (Ki approximately 4-6 microM), clemastine appeared to be significantly
      more potent, with a Ki of approximately 2 microM. These data demonstrate that
      classic histamine H1 receptor antagonists, available in over-the-counter
      preparations, inhibit CYP2D6 in vitro. Furthermore, the CYP2D6-inhibitory
      concentrations of these antihistamines are in the range of their expected hepatic
      blood concentrations, suggesting that, under specific circumstances, clinically
      relevant interactions between classic antihistamines and CYP2D6 substrates might
      occur.

PMID- 9616189
TI  - Biotransformation of the anthraquinones emodin and chrysophanol by cytochrome
      P450 enzymes. Bioactivation to genotoxic metabolites.
AB  - The studies presented here were designed to elucidate the enzymes involved in the
      biotransformation of naturally occurring 1, 8-dihydroxyanthraquinones and to
      investigate whether biotransformation of 1,8-dihydroxyanthraquinones may
      represent a bioactivation pathway. We first studied the metabolism of emodin (1,
      3,8-trihydroxy-6-methylanthraquinone), a compound present in pharmaceutical
      preparations. With rat liver microsomes, the formation of two emodin metabolites,
      omega-hydroxyemodin and 2-hydroxyemodin, was observed. The rates of formation of
      omega-hydroxyemodin were not different with microsomes from rats that had been
      pretreated with inducers for different cytochrome P450 enzymes. Thus, the
      formation of omega-hydroxyemodin seems to be catalyzed by several cytochrome P450
      enzymes at low rates. The formation of 2-hydroxyemodin was increased in liver
      microsomes from 3-methylcholanthrene-pretreated rats and was inhibited by alpha
      naphthoflavone, by an anti-rat cytochrome P450 1A1/2 antibody, and, to a lesser
      degree, by an anti-rat cytochrome P450 1A1 antibody. These data suggest the
      involvement of cytochrome P450 1A2 in the formation of this metabolite. However,
      other cytochrome P450 enzymes also seem to catalyze this reaction. The
      anthraquinone chrysophanol (1,8-dihydroxy-3-methylanthraquinone) is transformed,
      in a cytochrome P450-dependent oxidation, to aloe-emodin (1, 8-dihydroxy-3
      hydroxymethylanthraquinone) as the major product formed. The mutagenicity of the
      parent dihydroxyanthraquinones and their metabolites was compared in the in vitro
      micronucleus test in mouse lymphoma L5178Y cells. 2-Hydroxyemodin induced much
      higher micronucleus frequencies, compared with emodin. omega-Hydroxyemodin
      induced lower micronucleus frequencies, compared with emodin. Aloe-emodin induced
      significantly higher micronucleus frequencies than did chrysophanol. These data
      indicate that the cytochrome P450-dependent biotransformation of emodin and
      chrysophanol may represent bioactivation pathways for these compounds.

PMID- 9616190
TI  - Thiol agents separate nitric oxide formation from vasodilation induced by
      glyceryl trinitrate.
AB  - The role of nitric oxide (NO) and thiol-containing compounds in glyceryl
      trinitrate (GTN)-induced vasodilation was investigated using the thiol-alkylating
      agent N-ethylmaleimide (NEM). Bovine pulmonary artery (BPA) rings were
      submaximally contracted with K+ and exposed to increasing concentrations of GTN
      after a 30-min incubation with 50 microM NEM. NEM decreased maximal relaxation
      (10 microM GTN) by 20%, compared with controls. Treatment with 5 mM L-cysteine
      for 30 min before incubation with 50 microM NEM (protection protocol) prevented
      this decrease in GTN-induced relaxation, but 5 mM D-cysteine did not. Treatment
      of BPA rings with 5 mM L-cysteine after NEM treatment (reversal protocol) did not
      reverse the effect of NEM to decrease relaxation inducible by GTN. NO production
      from 30 microM GTN (chemiluminescence-headspace gas method) in the presence of
      BPA strips was 46.7 +/- 19.4 pmol NO/g tissue after 10 min of incubation and 76.4
      +/- 10.4 pmol NO/g tissue after 20 min. After a 30-min incubation with 50 microM
      NEM, NO was not detected at either time point. NO production from GTN by BPA
      strips, with either the protection or reversal protocol, was elevated
      approximately 2-fold at both time points, compared with controls. No increase in
      NO production from GTN was observed at either time point for tissues treated with
      5 mM D-cysteine using the same protocols. These results are consistent with the
      concept that thiol compounds play a role in the mechanism of GTN-induced
      vasodilation, but they indicate that the mechanism of action of GTN and other
      organic nitrates is more complex than their acting as immediate prodrugs of NO.

PMID- 9616191
TI  - Metabolism of the human immunodeficiency virus protease inhibitors indinavir and
      ritonavir by human intestinal microsomes and expressed cytochrome P4503A4/3A5:
      mechanism-based inactivation of cytochrome P4503A by ritonavir.
AB  - Both ritonavir and indinavir were readily metabolized by human intestinal
      microsomes. Comparison of the patterns of metabolites in incubations with
      enterocyte microsomes and expressed cytochrome P450 (CYP) isozymes and
      immunoinhibition and chemical inhibition studies showed the essential role of the
      CYP3A subfamily in the metabolism of both protease inhibitors by the small
      intestine. Ritonavir was similarly biotransformed by microsomes containing
      expressed CYP3A4 or CYP3A5 isozymes (KM = 0.05-0.07 microM, Vmax = 1-1.4
      nmol/min/nmol CYP). In contrast, both the patterns of metabolites and the enzyme
      kinetic parameters for the metabolism of indinavir by expressed CYP3A5 (KM = 0.21
      microM, Vmax = 0.24 nmol/min/nmol CYP) and CYP3A4 (KM = 0.04 microM, Vmax = 0.68
      nmol/min/nmol CYP) were different. The biotransformation of both indinavir and
      ritonavir in human enterocyte microsomes was characterized by very low KM values
      (0.2-0.4 microM for indinavir and <0.1 microM for ritonavir). The Vmax for
      indinavir metabolism was greater in enterocyte (163 +/- 35 pmol/min/mg protein)
      than in liver (68 +/- 44 pmol/min/mg protein) microsomes. The metabolism of
      ritonavir in liver and enterocyte microsomes was associated with inactivation of
      CYP3A. The initial Vmax for ritonavir metabolism by enterocyte microsomes was 89
      +/- 59 pmol/min/mg protein. The apparent inactivation rate constants for
      intestinal CYP3A and expressed CYP3A4 were 0.078 and 0.135 min-1, respectively.
      Metabolic inactivation of CYP3A by ritonavir explains the improved
      bioavailability and pharmacokinetics of ritonavir and the sustained elevation of
      blood levels of other, concomitantly administered, substrates of CYP3A.

PMID- 9616192
TI  - Analysis of metabolite formation pharmacokinetics after intravenous and oral
      administration of the parent drug using inverse Laplace transformation.
AB  - Models describing the plasma concentration-time curves of generated metabolite
      after iv and oral drug administration are presented. Utilizing numerical inverse
      Laplace transformation, the method can readily be used for parameter estimation
      and model simulation in conjunction with appropriate curve-fitting software. The
      approach is not limited to compartment modeling and can be applied to any linear
      pharmacokinetic system exhibiting hepatic and renal elimination of the parent
      drug. The model is formulated for single and multiple dosing of the precursor,
      including bolus doses and/or infusions for iv administration and sustained
      release dosage forms for oral administration.

PMID- 9616193
TI  - N-Dealkylation and hydroxylation of ebastine by human liver cytochrome P450.
AB  - Ebastine [4'-tert-butyl-4-[4-(diphenylmethoxy)piperidino]butyro phe- none] is a
      new-generation, nonsedative, H1 antihistamine. The present study was performed to
      characterize the cytochrome P450 (CYP) isoforms responsible for ebastine N
      dealkylation and hydroxylation. Human liver microsomes metabolized ebastine to
      two major metabolites, i.e. a desbutyrophenone metabolite (des-BP) and
      hydroxyebastine (M-OH), and the ratio of Vmax values was 3:1. N-Dealkylation
      yielded des-BP, whereas M-OH, an hydroxylation product, could be further oxidized
      to the pharmacologically active carebastine. In a panel of 14 human liver
      microsomal preparations, the rate of dealkylation showed a highly significant
      correlation with CYP3A-mediated testosterone 6beta-hydroxylation but not with
      reactions of seven other CYP isoforms. However, there was no correlation between
      the two pathways for ebastine (dealkylation and hydroxylation). Differential
      chemical inhibition in liver microsomes, in which dealkylation was more sensitive
      than hydroxylation, was demonstrated with ketoconazole, troleandomycin,
      cyclosporin A, and midazolam. Anti-CYP3A antibodies markedly reduced the
      dealkylation rate (>95%) in liver microsomes but exhibited insignificant effects
      on hydroxylation (<5%). Among 12 cDNA-expressed human CYP isoforms, which account
      for up to 70% of the total CYP enzyme content in human liver, CYP3A4 alone
      metabolized ebastine; the ratio of des-BP to M-OH formation was 12:1. This ratio
      for metabolism by the pure enzyme was much larger than the ratio (3:1) observed
      for the microsomal reaction mixture. This change in ratio, which is attributed to
      a decrease in M-OH formation, indicates that, although ebastine is metabolized to
      two major metabolites, N-dealkylation to des-BP is mediated by CYP3A, whereas
      hydroxylation to M-OH appears to be mediated mainly by unidentified enzymes other
      than CYP3A.

PMID- 9616194
TI  - Trazodone is metabolized to m-chlorophenylpiperazine by CYP3A4 from human
      sources.
AB  - The metabolism of the antidepressant drug trazodone to its active metabolite, m
      chlorophenylpiperazine (mCPP), was studied in vitro using human liver microsomal
      preparations and cDNA-expressed human cytochrome P450 (P450) enzymes. The
      kinetics of mCPP formation from trazodone were determined, and three in vitro
      experiments were performed to identify the major P450 enzyme involved. Trazodone
      (100 microM) was incubated with 16 different human liver microsomal preparations
      characterized for activities of 7 different P450 isoforms. The production of mCPP
      correlated significantly with activity of cytochrome P4503A4 (CYP3A4) only.
      Trazodone (100 microM) was then incubated with microsomes from cells expressing
      human CYP1A1, CYP1A2, CYP2C8, CYP2C9arg, CYP2C9cys, CYP2C19, CYP2D6, or CYP3A4.
      Only incubations with CYP3A4 resulted in mCPP formation. In the third experiment,
      the CYP3A4 inhibitor ketoconazole was found to inhibit mCPP formation
      concentration dependently in both human liver microsomes and in microsomes from
      cells expressing human CYP3A4. The present results indicate that trazodone is a
      substrate for CYP3A4, that CYP3A4 is a major isoform involved in the production
      of mCPP from trazodone, and that there is the possibility of drug-drug
      interactions with trazodone and other substrates, inducers and/or inhibitors of
      CYP3A4.

PMID- 9616195
TI  - Pharmacokinetics of meloxicam in animals and the relevance to humans.
AB  - The pharmacokinetic profile of the new nonsteroidal anti-inflammatory drug
      meloxicam was investigated in a number of animal species, including mice, rats,
      dogs, mini-pigs, and baboons, after administration of [14C]meloxicam. The plasma
      concentration-time profiles for meloxicam in rats and dogs were comparable to
      that in humans, whereas there were marked differences between humans and mice,
      mini-pigs, and baboons. The highest tissue concentrations of meloxicam in rats
      and mini-pigs were seen in the liver and kidneys. In contrast, low concentrations
      of meloxicam were found in the central nervous system, compared with those in
      plasma. The excretion balance in mini-pigs resembled that in humans, with almost
      equal concentrations being eliminated in the urine and the feces. As in humans,
      meloxicam circulated mainly in the form of the parent compound in the plasma of
      mice, rats, dogs, mini-pigs, and baboons. The main metabolites in rats, mini
      pigs, and humans were a 5'-hydroxymethyl derivative (AF-UH 1 SE) and a 5'-carboxy
      metabolite (UH-AC 110 SE). The percentage of meloxicam binding to protein was
      higher in rats and humans (>99%) than in other species. The pharmacokinetic
      profile of meloxicam in rats most closely resembles that in humans; therefore,
      reliable clinical predictions can be made from studies in this rodent species.

PMID- 9616196
TI  - Physiologically based pharmacokinetics model of primidone and its metabolites
      phenobarbital and phenylethylmalonamide in humans, rats, and mice.
AB  - Physiologically based pharmacokinetic modeling of the parent chemical primidone
      and its two metabolites phenobarbital and phenylethylmalonamide (PEMA) was
      applied to investigate the differences of primidone metabolism among humans,
      rats, and mice. The model simulated previously published pharmacokinetic data of
      the parent chemical and its metabolites in plasma and brain tissues from separate
      studies of the three species. Metabolism of primidone and its metabolites varied
      widely among a sample of three human subjects from two separate studies.
      Estimated primidone metabolism, as expressed by the maximal velocity Vmax, ranged
      from 0 to 0.24 mg. min-1.kg-1 for the production of phenobarbital and from 0.003
      to 0. 02 mg.min-1.kg-1 for the production of PEMA among three human subjects.
      Further model simulations indicated that rats were more efficient at producing
      and clearing phenobarbital and PEMA than mice. However, the overall metabolism
      profile of primidone and its metabolites in mice indicated that mice were at
      higher risk of toxicity owing to higher residence of phenobarbital in their
      tissues and owing to the carcinogenic potential of phenobarbital as illustrated
      in long-term bioassays. This result was in agreement with a recently finished
      National Toxicology Program (NTP) carcinogenicity study of primidone in rats and
      mice.

PMID- 9616197
TI  - Effect of hypoalbuminemia on the disposition of theophylline. Comparative study
      with Sprague-Dawley rats and a mutant Sprague-Dawley hyperlipidemic strain with
      hypoalbuminemia.
AB  - We demonstrated the effect of hypoalbuminemia on theophylline disposition in
      rats. The pharmacokinetic parameters in Sprague-Dawley rats (SDRs) were compared
      with those in spontaneously hyperlipidemic rats (HLRs), which had approximately
      one half the serum albumin concentration of the SDRs, after a single 10 mg/kg
      injection (iv) of theophylline. Theophylline clearance (CL) in the HLRs was
      increased 1.6-fold, and the AUC was decreased by 36%. Although the elimination
      t1/2 was not significantly different between the two types of rats, the
      distribution volume (Vd) was increased significantly in the HLRs, compared with
      the SDRs. The free theophylline concentration in the SDRs was one half of the
      total concentration. In contrast, the free theophylline concentration in the HLRs
      was approximately equal to the total concentration. The enzymatic activities and
      apoprotein expression levels of CYP1A were decreased significantly in the HLRs,
      compared with the SDRs. The total theophylline CL was increased in HLRs with
      hypoalbuminemia, even though they exhibited lower enzymatic activity and CYP1A
      expression than did the SDRs. Because the unbound fraction and Vd of theophylline
      in HLRs were much larger than those in SDRs, we conclude that hypoalbuminemia may
      contribute to an increase in the Vd and a decrease in the CL for theophylline.

PMID- 9616198
TI  - Tissue-specific expression of rat sulfotransferase messenger RNAs.
AB  - The present study examined the tissue distribution of rat sulfotransferase (SULT)
      mRNAs to assess the relative contribution of each tissue to the process of
      sulfation. The SULT isoforms examined were male-dominant SULTs (SULT1A1, SULT1C1,
      and SULT1E2), female-dominant SULTs (SULT20/21, SULT40/41, and SULT60), and the
      recently cloned, non sex-dependent SULT (SULT1B1). SULTs fall into two distinct
      classes based on substrate preference: phenol SULTs (SULT1A1, SULT1B1, SULT1C1,
      and SULT1E2) and hydroxysteroid SULTs (SULT20/21, SULT40/41, and SULT60). The
      following tissues were analyzed for SULT mRNA expression: liver, brain, lung,
      heart, intestine, kidney, adrenal, prostate, testes, ovary, uterus, and spleen by
      Northern blot analysis with [alpha-32P]dATP-labeled oligonucleotide probes
      specific for individual SULT mRNAs. Tissue expression levels of each SULT were
      quantified and compared with liver expression by phosphor-autoradiographic
      analysis. Male-dominant SULT expression was observed in many organs, where
      SULT1A1 was expressed in liver, brain, lung, heart, intestine, kidney, adrenal,
      testes, and spleen; SULT1C1 expression was observed in liver, kidney, and spleen;
      and SULT1E2 expression was observed only in liver and heart. The female-dominant
      SULTs exhibited a more limited tissue distribution. Expression of SULT20/21 and
      SULT60 was observed only in liver and adrenal gland, whereas SULT40/41 expression
      was observed only in liver. SULT1B1 was expressed to a similar extent in tissues
      of male and female rats and was detected in liver, intestine, and kidney.
      Expression of SULT mRNAs in liver was much higher than in other tissues, except
      for SULT1A1, which exhibited substantial expression in lung, and SULT1B1, which
      was expressed at relatively high levels in intestine. These studies indicate that
      liver is the most diverse organ with respect to expression of multiple SULT
      enzymes and is therefore the most significant organ involved in sulfation. In
      contrast to liver, extrahepatic tissues express specific SULT mRNAs, and this may
      be important for the physiological role of each tissue.

PMID- 9616199
TI  - Human halothane reduction in vitro by cytochrome P450 2A6 and 3A4: identification
      of low and high KM isoforms.

PMID- 9616200
TI  - Promethean thymus?

PMID- 9616201
TI  - High prevalence of thymic tissue in adults with human immunodeficiency virus-1
      infection.
AB  - The thymus in adults infected with the HIV-1 is generally thought to be inactive,
      both because of age-related involution and viral destruction. We have revisited
      the question of thymic function in adults, using chest-computed tomography (CT)
      to measure thymic tissue in HIV-1-seropositive (n = 99) or HIV-1-seronegative (n
      = 32) subjects, and correlating these results with the level of circulating
      CD4(+) and CD8(+) T cells that are phenotypically described as naive thymic
      emigrants. Abundant thymic tissue was detectable in many (47/99) HIV-1
      seropositive adults, aged 20-59. Independent of age, radiographic demonstration
      of thymic tissue was significantly associated with both a higher CD4(+) T cell
      count (P = 0.02) and a higher percentage and absolute number of circulating naive
      (CD45RA+CD62L+) CD4(+) T cells (P < 0.04). The prevalence of an abundant thymus
      was especially high in younger HIV-1-seropositive adults (</= 39 yr) with CD4
      counts in the range 300-500 cells/microl and in older subjects (> 40 yr)
      regardless of CD4 count (P = 0.03). These studies suggest that the thymus is
      functional in some but not all adults with HIV-1 disease.

PMID- 9616202
TI  - Late blockade of T cell costimulation interrupts progression of experimental
      chronic allograft rejection.
AB  - Early blockade of T cell-costimulatory activation pathways prevents development
      of experimental chronic allograft rejection. Ongoing T cell recognition of
      alloantigen and activation may also play an important role in progression of
      chronic rejection, but definitive evidence is lacking. We used the fusion protein
      CTLA4Ig to block CD28-B7 T cell costimulation late after the onset of initial
      graft injury. Using the F334 into LEW rat model of chronic renal allograft
      rejection, transplant recipients were treated with a 10-d course of cyclosporine,
      and a subgroup received a single injection of CTLA4Ig at 8 wk after transplant.
      Functionally, CTLA4Ig administration prevented development of progressive
      proteinuria (14.3+/-4.1 mg/24 h versus 41.0+/-12.0 mg/24 h at 24 wk after
      transplant, P < 0.05). Histologically, graft mononuclear cell infiltration,
      glomerular hypertrophy, focal and segmental glomerulosclerosis, and intimal
      vascular hyperplasia were all attenuated in CTLA4Ig-treated animals. Lastly,
      reverse transcriptase-PCR and immunohistologic studies showed a significant
      reduction in the intragraft expression of key products of T cell and macrophage
      activation, and upregulation of what have recently been termed as "protective"
      genes, including the bcl family members, Bcl-2 and Bcl-xL, and hemoxygenase. Our
      data are the first to demonstrate that blocking T cell-costimulatory activation
      late after transplantation, after initial graft injury, prevents progression of
      chronic allograft rejection supporting the hypothesis that ongoing T cell
      recognition of alloantigen and activation are key mediators of ongoing chronic
      allograft rejection.

PMID- 9616203
TI  - Molecular identification of the role of voltage-gated K+ channels, Kv1.5 and
      Kv2.1, in hypoxic pulmonary vasoconstriction and control of resting membrane
      potential in rat pulmonary artery myocytes.
AB  - Hypoxia initiates pulmonary vasoconstriction (HPV) by inhibiting one or more
      voltage-gated potassium channels (Kv) in the pulmonary artery smooth muscle cells
      (PASMCs) of resistance arteries. The resulting membrane depolarization increases
      opening of voltage-gated calcium channels, raising cytosolic Ca2+ and initiating
      HPV. There are presently nine families of Kv channels known and pharmacological
      inhibitors lack the specificity to distinguish those involved in control of
      resting membrane potential (Em) or HPV. However, the Kv channels involved in Em
      and HPV have characteristic electrophysiological and pharmacological properties
      which suggest their molecular identity. They are slowly inactivating, delayed
      rectifier currents, inhibited by 4-aminopyridine (4-AP) but insensitive to
      charybdotoxin. Candidate Kv channels with these traits (Kv1.5 and Kv2.1) were
      studied. Antibodies were used to immunolocalize and functionally characterize the
      contribution of Kv1. 5 and Kv2.1 to PASMC electrophysiology and vascular tone.
      Immunoblotting confirmed the presence of Kv1.1, 1.2, 1.3, 1.5, 1.6, and 2.1, but
      not Kv1.4, in PASMCs. Intracellular administration of anti-Kv2.1 inhibited whole
      cell K+ current (IK) and depolarized Em. Anti-Kv2.1 also elevated resting tension
      and diminished 4-AP-induced vasoconstriction in membrane-permeabilized pulmonary
      artery rings. Anti-Kv1.5 inhibited IK and selectively reduced the rise in [Ca2+]i
      and constriction caused by hypoxia and 4-AP. However, anti-Kv1.5 neither caused
      depolarization nor elevated basal pulmonary artery tone. This study demonstrates
      that antibodies can be used to dissect the whole cell K+ currents in mammalian
      cells. We conclude that Kv2. 1 is an important determinant of resting Em in
      PASMCs from resistance arteries. Both Kv2.1 and Kv1.5 contribute to the
      initiation of HPV.

PMID- 9616204
TI  - Activation of cholesterol synthesis in preference to fatty acid synthesis in
      liver and adipose tissue of transgenic mice overproducing sterol regulatory
      element-binding protein-2.
AB  - We produced transgenic mice that express a dominant-positive truncated form of
      sterol regulatory element-binding protein-2 (SREBP-2) in liver and adipose
      tissue. The encoded protein lacks the membrane-binding and COOH-terminal
      regulatory domains, and it is therefore not susceptible to negative regulation by
      cholesterol. Livers from the transgenic mice showed increases in mRNAs encoding
      multiple enzymes of cholesterol biosynthesis, the LDL receptor, and fatty acid
      biosynthesis. The elevations in mRNA for 3-hydroxy-3-methylglutaryl coenzyme A
      (HMG CoA) synthase and HMG CoA reductase were especially marked (13-fold and 75
      fold, respectively). As a result, the transgenic livers showed a 28-fold increase
      in the rate of cholesterol synthesis and a lesser fourfold increase in fatty acid
      synthesis, as measured by intraperitoneal injection of [3H]water. These results
      contrast with previously reported effects of dominant-positive SREBP-1a, which
      activated fatty acid synthesis more than cholesterol synthesis. In adipose tissue
      of the SREBP-2 transgenics, the mRNAs for cholesterol biosynthetic enzymes were
      elevated, but the mRNAs for fatty acid biosynthetic enzymes were not. We conclude
      that SREBP-2 is a relatively selective activator of cholesterol synthesis, as
      opposed to fatty acid synthesis, in liver and adipose tissue of mice.

PMID- 9616205
TI  - An acetylcholine receptor alpha subunit promoter confers intrathymic expression
      in transgenic mice. Implications for tolerance of a transgenic self-antigen and
      for autoreactivity in myasthenia gravis.
AB  - Myasthenia gravis (MG) is an autoimmune disease targeting the skeletal muscle
      acetylcholine receptor (AChR). Although the autoantigen is present in the thymus,
      it is not tolerated in MG patients. In addition, the nature of the cell bearing
      the autoantigen is controversial. To approach these questions, we used two
      lineages of transgenic mice in which the beta-galactosidase (beta-gal) gene is
      under the control of a 842-bp (Tg1) or a 3300-bp promoter fragment (Tg2) of the
      chick muscle alpha subunit AChR gene. In addition to expression in muscle cells,
      thymic expression was observed in both mouse lines (mainly in myoid cells in Tg1
      and myoid cells and epithelial cells in Tg2). After challenge with beta-gal, Tg1
      mice produced Th2-dependent anti-beta-gal antibodies, while Tg2 mice were almost
      unresponsive. By contrast, in a proliferation assay both Tg lines were
      unresponsive to beta-gal. Cells from Tg1 mice produce Th2-dependent cytokine
      whereas cells from Tg2 mice were nonproducing in response to beta-gal. These data
      indicate that the level of expression in Tg1 mice could be sufficient to induce
      tolerance of Th1 cells but not of Th2 cells, while both populations are tolerated
      in Tg2 mice. These findings are compatible with the hypothesis that AChR
      expression is not sufficiently abundant in MG thymus to induce a full tolerance.

PMID- 9616206
TI  - Cathepsin S activity regulates antigen presentation and immunity.
AB  - MHC class II molecules display antigenic peptides on cell surfaces for
      recognition by CD4(+) T cells. Proteolysis is required in this process both for
      degradation of invariant chain (Ii) from class II-Ii complexes to allow
      subsequent binding of peptides, and for generation of the antigenic peptides. The
      cysteine endoprotease, cathepsin S, mediates Ii degradation in human and mouse
      antigen-presenting cells. Studies described here examine the functional
      significance of cathepsin S inhibition on antigen presentation and immunity.
      Specific inhibition of cathepsin S in A20 cells markedly impaired presentation of
      an ovalbumin epitope by interfering with class II-peptide binding, not by
      obstructing generation of the antigen. Administration of a cathepsin S inhibitor
      to mice in vivo selectively inhibited activity of cathepsin S in splenocytes,
      resulting in accumulation of a class II-associated Ii breakdown product,
      attenuation of class II-peptide complex formation, and inhibition of antigen
      presentation. Mice treated with inhibitor had an attenuated antibody response
      when immunized with ovalbumin but not the T cell-independent antigen TNP-Ficoll.
      In a mouse model of pulmonary hypersensitivity, treatment with the inhibitor also
      abrogated a rise in IgE titers and profoundly blocked eosinophilic infiltration
      in the lung. Thus, inhibition of cathepsin S in vivo alters Ii processing,
      antigen presentation, and immunity. These data identify selective inhibition of
      cysteine proteases as a potential therapeutic strategy for asthma and autoimmune
      disease processes.

PMID- 9616207
TI  - Mutation in the signal-transducing chain of the interferon-gamma receptor and
      susceptibility to mycobacterial infection.
AB  - IFN-gamma is critical in the immune response to mycobacterial infections, and
      deficits in IFN-gamma production and response have been associated with
      disseminated nontuberculous mycobacterial infections. Mutations in the IFN-gamma
      receptor ligand-binding chain (IFNgammaR1) have been shown to confer
      susceptibility to severe infection with nontuberculous mycobacteria. However,
      mutations in the IFN-gamma receptor signal-transducing chain (IFNgammaR2) have
      not been described. We describe a child with disseminated Mycobacterium fortuitum
      and M. avium complex infections and absent IFN-gamma signaling due to a mutation
      in the extracellular domain of IFNgammaR2. In vitro cytokine production by
      patient PBMCs showed 75% less PHA-induced IFN-gamma production than in normal
      cells, while patient PHA-induced TNF-alpha production was normal. The normal
      augmentation of TNF-alpha production when IFN-gamma was added to endotoxin was
      absent from patient cells. Expression of IFNgammaR1 was normal, but there was no
      phosphorylation of Stat1 in response to IFN-gamma stimulation. DNA sequence
      analysis of the gene for IFNgammaR2 showed a homozygous dinucleotide deletion at
      nucleotides 278 and 279, resulting in a premature stop codon in the protein
      extracellular domain. This novel gene defect associated with disseminated
      nontuberculous mycobacterial infection emphasizes the critical role that IFN
      gamma plays in host defense against mycobacteria.

PMID- 9616208
TI  - A fatty acid- dependent step is critically important for both glucose- and non
      glucose-stimulated insulin secretion.
AB  - Lowering of the plasma FFA level in intact fasted rats by infusion of nicotinic
      acid (NA) caused essentially complete ablation of insulin secretion (IS) in
      response to a subsequent intravenous bolus of arginine, leucine, or glibenclamide
      (as previously found using glucose as the beta-cell stimulus). However, in all
      cases, IS became supranormal when a high FFA level was maintained by co-infusion
      of lard oil plus heparin. Each of these secretagogues elicited little, if any, IS
      from the isolated, perfused "fasted" pancreas when tested simply on the
      background of 3 mM glucose, but all became extremely potent when 0.5 mM palmitate
      was also included in the medium. Similarly, IS from the perfused pancreas, in
      response to depolarizing concentrations of KCl, was markedly potentiated by
      palmitate. As was the case with intravenous glucose administration, fed animals
      produced an equally robust insulin response to glibenclamide regardless of
      whether their low basal FFA concentration was further reduced by NA. In the
      fasted state, arginine-induced glucagon secretion appeared to be independent of
      the prevailing FFA concentration. The findings establish that the essential role
      of circulating FFA for glucose-stimulated IS after food deprivation also applies
      in the case of nonglucose secretagogues. In addition, they imply that (i) a fatty
      acid-derived lipid moiety, which plays a pivotal role in IS, is lost from the
      pancreatic beta-cell during fasting; (ii) in the fasted state, the elevated level
      of plasma FFA compensates for this deficit; and (iii) the lipid factor acts at a
      late step in the insulin secretory pathway that is common to the action of a wide
      variety of secretagogues.

PMID- 9616209
TI  - Evidence for defects in the trafficking and translocation of GLUT4 glucose
      transporters in skeletal muscle as a cause of human insulin resistance.
AB  - Insulin resistance is instrumental in the pathogenesis of type 2 diabetes
      mellitus and the Insulin Resistance Syndrome. While insulin resistance involves
      decreased glucose transport activity in skeletal muscle, its molecular basis is
      unknown. Since muscle GLUT4 glucose transporter levels are normal in type 2
      diabetes, we have tested the hypothesis that insulin resistance is due to
      impaired translocation of intracellular GLUT4 to sarcolemma. Both insulin
      sensitive and insulin-resistant nondiabetic subgroups were studied, in addition
      to type 2 diabetic patients. Biopsies were obtained from basal and insulin
      stimulated muscle, and membranes were subfractionated on discontinuous sucrose
      density gradients to equilibrium or under nonequilibrium conditions after a
      shortened centrifugation time. In equilibrium fractions from basal muscle, GLUT4
      was decreased by 25-29% in both 25 and 28% sucrose density fractions and
      increased twofold in both the 32% sucrose fraction and bottom pellet in diabetics
      compared with insulin-sensitive controls, without any differences in membrane
      markers (phospholemman, phosphalamban, dihydropyridine-binding complex alpha-1
      subunit). Thus, insulin resistance was associated with redistribution of GLUT4 to
      denser membrane vesicles. No effects of insulin stimulation on GLUT4 localization
      were observed. In non-equilibrium fractions, insulin led to small GLUT4
      decrements in the 25 and 28% sucrose fractions and increased GLUT4 in the 32%
      sucrose fraction by 2.8-fold over basal in insulin-sensitive but only by 1.5-fold
      in both insulin-resistant and diabetic subgroups. The GLUT4 increments in the 32%
      sucrose fraction were correlated with maximal in vivo glucose disposal rates (r =
      +0.51, P = 0.026), and, therefore, represented GLUT4 recruitment to sarcolemma or
      a quantitative marker for this process. Similar to GLUT4, the insulin-regulated
      aminopeptidase (vp165) was redistributed to a dense membrane compartment and did
      not translocate in response to insulin in insulin-resistant subgroups. In
      conclusion, insulin alters the subcellular localization of GLUT4 vesicles in
      human muscle, and this effect is impaired equally in insulin-resistant subjects
      with and without diabetes. This translocation defect is associated with abnormal
      accumulation of GLUT4 in a dense membrane compartment demonstrable in basal
      muscle. We have previously observed a similar pattern of defects causing insulin
      resistance in human adipocytes. Based on these data, we propose that human
      insulin resistance involves a defect in GLUT4 traffic and targeting leading to
      accumulation in a dense membrane compartment from which insulin is unable to
      recruit GLUT4 to the cell surface.

PMID- 9616210
TI  - A selective human beta3 adrenergic receptor agonist increases metabolic rate in
      rhesus monkeys.
AB  - Activation of beta3 adrenergic receptors on the surface of adipocytes leads to
      increases in intracellular cAMP and stimulation of lipolysis. In brown adipose
      tissue, this serves to up-regulate and activate the mitochondrial uncoupling
      protein 1, which mediates a proton conductance pathway that uncouples oxidative
      phosphorylation, leading to a net increase in energy expenditure. While chronic
      treatment with beta3 agonists in nonprimate species leads to uncoupling protein 1
      up-regulation and weight loss, the relevance of this mechanism to energy
      metabolism in primates, which have much lower levels of brown adipose tissue, has
      been questioned. With the discovery of L-755,507, a potent and selective partial
      agonist for both human and rhesus beta3 receptors, we now demonstrate that acute
      exposure of rhesus monkeys to a beta3 agonist elicits lipolysis and metabolic
      rate elevation, and that chronic exposure increases uncoupling protein 1
      expression in rhesus brown adipose tissue. These data suggest a role for beta3
      agonists in the treatment of human obesity.

PMID- 9616211
TI  - The expression of Fas Ligand by macrophages and its upregulation by human
      immunodeficiency virus infection.
AB  - Fas/Fas Ligand (FasL) interactions play a significant role in peripheral T
      lymphocyte homeostasis and in certain pathological states characterized by T cell
      depletion. In this study, we demonstrate that antigen-presenting cells such as
      monocyte-derived human macrophages (MDM) but not monocyte-derived dendritic cells
      express basal levels of FasL. HIV infection of MDM increases FasL protein
      expression independent of posttranslational mechanisms, thus highlighting the
      virus-induced transcriptional upregulation of FasL. The in vitro relevance of
      these observations is confirmed in human lymphoid tissue. FasL protein expression
      is constitutive and restricted to tissue macrophages and not dendritic cells.
      Moreover, a significant increase in macrophage-associated FasL is observed in
      lymphoid tissue from HIV (+) individuals (P < 0.001), which is further supported
      by increased levels of FasL mRNA using in situ hybridization. The degree of FasL
      protein expression in vivo correlates with the degree of tissue apoptosis (r =
      0.761, P < 0. 001), which is significantly increased in tissue from HIV-infected
      patients (P < 0.001). These results identify human tissue macrophages as a
      relevant source for FasL expression in vitro and in vivo and highlight the
      potential role of FasL expression in the immunopathogenesis of HIV infection.

PMID- 9616212
TI  - In vivo tumor transfection with superantigen plus cytokine genes induces tumor
      regression and prolongs survival in dogs with malignant melanoma.
AB  - In vivo transfection of established tumors with immunostimulatory genes can
      elicit antitumor immunity. Therefore, we evaluated the safety and efficacy of
      intratumoral injections of a bacterial superantigen with a cytokine gene in dogs
      with malignant melanoma, a spontaneous and highly malignant canine tumor. 26 dogs
      with melanoma were treated with lipid-complexed plasmid DNA encoding
      staphylococcal enterotoxin B and either GM-CSF or IL-2. Dogs were evaluated for
      treatment-associated toxicity, tumor responses, immunologic responses, and
      survival times. The overall response rate (complete or partial remissions) for
      all 26 dogs was 46% (12 of 26), and was highest in patients with smaller tumors.
      Toxicity was minimal or absent in all dogs. Injected tumors developed marked
      infiltrates of CD4+ and CD8+ T cells and macrophages, and tumor regression was
      associated with development of high levels of antitumor cytotoxic T lymphocyte
      activity in peripheral blood lymphocytes. Survival times for animals with stage
      III melanomas treated by intratumoral gene therapy were prolonged significantly
      compared with animals treated with surgical tumor excision only. Thus, local
      tumor transfection with superantigen and cytokine genes was capable of inducing
      both local and systemic antitumor immunity in an outbred animal with a
      spontaneously developing malignant tumor.

PMID- 9616213
TI  - Dilated cardiomyopathy in transgenic mice expressing a dominant-negative CREB
      transcription factor in the heart.
AB  - Idiopathic-dilated cardiomyopathy (IDC) is a common primary myocardial disease of
      unknown etiology characterized by progressive biventricular failure, cardiac
      dilatation, and premature mortality. Here we show that transgenic mice expressing
      a dominant-negative form of the CREB transcription factor (CREBA133) under the
      control of the cardiac myocyte-specific alpha-MHC promoter develop dilated
      cardiomyopathy that closely resembles many of the anatomical, physiological, and
      clinical features of human IDC. Between 2 and 20 wk of age, these mice develop
      four chamber cardiac dilatation, decreased systolic and diastolic left
      ventricular function, and attenuated contractile responses to the beta-adrenergic
      agonist, isoproterenol. Histologically, the CREBA133 hearts demonstrated both
      atrophic and hypertrophied fibers as well as significant interstitial fibrosis.
      These anatomical and hemodynamic changes were associated with hepatic congestion
      and peripheral edema, intracardiac thrombi, and premature mortality. Taken
      together, these results implicate CREB as an important regulator of cardiac
      myocyte function and provide a genetic model of dilated cardiomyopathy which
      should facilitate studies of both the pathogenesis and therapy of this clinically
      important disorder.

PMID- 9616214
TI  - In vivo expression of neutrophil inhibitory factor via gene transfer prevents
      lipopolysaccharide-induced lung neutrophil infiltration and injury by a beta2
      integrin-dependent mechanism.
AB  - The binding of beta2 (CD18) integrins on PMN cell membrane to intercellular
      adhesion molecule (ICAM) counter-receptors on the surface of vascular endothelial
      cells mediates PMN adhesion to endothelial cells. Neutrophil inhibitory factor
      (NIF), a 41-kD glycoprotein isolated from the canine hookworm (Ancylostoma
      caninum), is a beta2 integrin antagonist that inhibits PMN adhesion to
      endothelial cells. We transferred the NIF gene into CD1 mouse lungs by
      intravenous injection of cationic liposomes to study the effects of in vivo NIF
      expression on LPS-induced lung PMN sequestration and the development of lung
      injury. RT-PCR and Northern blot analysis indicated the lung-selective expression
      of the NIF transgene, and immunocytochemistry showed prominent NIF expression in
      pulmonary microvessel endothelial cells. NIF staining was also observed in
      intraluminal leukocytes present in pulmonary microvessels. This may be the result
      of NIF binding to leukocytes after its secretion from the transduced lung cells,
      since there was no evidence of NIF gene expression in circulating leukocytes.
      Pulmonary vascular NIF expression abrogated the lung tissue PMN uptake and
      airspace migration of PMN and prevented lung vascular injury (as measured by the
      lung tissue uptake of [125I]labeled albumin) after the intraperitoneal LPS
      challenge (200 microg/mouse). Expression of a control protein, chloramphenicol
      acetyltransferase (CAT), by the same strategy, had no effect on these responses.
      In vitro studies showed that NIF prevented mouse PMN adhesion consistent with the
      inhibition of lung uptake after LPS challenge in NIF transgene-expressing mice.
      We conclude that pulmonary vascular expression of NIF, a specific beta2 integrin-
      binding protein, is a potentially useful gene transfer strategy in modulating the
      infiltration of PMN across the alveolar-capillary epithelial barrier and in
      preventing lung vascular endothelial injury.

PMID- 9616215
TI  - Leukocyte Adhesion Deficiency Type II is a generalized defect of de novo GDP
      fucose biosynthesis. Endothelial cell fucosylation is not required for neutrophil
      rolling on human nonlymphoid endothelium.
AB  - Leukocyte Adhesion Deficiency Type II (LAD II) is a recently described syndrome
      and the two patients with this defect lack fucosylated glycoconjugates. These
      glycoconjugates include the selectin ligand, sialyl LewisX, and various
      fucosylated blood group antigens. To date, the molecular anomaly in these
      patients has not been identified. We localized the defect in LAD II to the de
      novo pathway of GDP-fucose biosynthesis, by inducing cell-surface expression of
      fucosylated glycoconjugates after exposure of lymphoblastoid cell lines from the
      LAD II patients to exogenous fucose. This defect is not restricted to
      hematopoietic cells, since similar findings were elicited in both human umbilical
      vein endothelial cells (HUVEC) and fibroblasts derived from an affected abortus.
      We have used these LAD II endothelial cells to examine the consequence of
      fucosylation of endothelial cells on the rolling of normal neutrophils in an in
      vitro assay. Neutrophil rolling on LPS-treated normal and LAD II HUVEC was
      inhibited by an E-selectin monoclonal antibody at both high and low shear rates.
      LAD II HUVEC lacking fucosylated glycoproteins supported leukocyte rolling to a
      similar degree as normal HUVEC or LAD II cells that were fucose-fed. At low shear
      rates, an L-selectin antibody inhibited neutrophil rolling to a similar degree
      whether the LAD II cells had been fucose-fed or not. These findings suggest that
      fucosylation of nonlymphoid endothelial cells does not play a major role in
      neutrophil rolling and that fucose is not a critical moiety on the L-selectin
      ligand(s) on endothelial cells of the systemic vasculature.

PMID- 9616216
TI  - Long-term survival of skin allografts induced by donor splenocytes and anti-CD154
      antibody in thymectomized mice requires CD4(+) T cells, interferon-gamma, and
      CTLA4.
AB  - Treatment of C57BL/6 mice with one transfusion of BALB/c spleen cells and anti
      CD154 (anti-CD40-ligand) antibody permits BALB/c islet grafts to survive
      indefinitely and BALB/c skin grafts to survive for approximately 50 d without
      further intervention. The protocol induces long-term allograft survival, but the
      mechanism is unknown. We now report: (a) addition of thymectomy to the protocol
      permitted skin allografts to survive for > 100 d, suggesting that graft rejection
      in euthymic mice results from thymic export of alloreactive T cells. (b) Clonal
      deletion is not the mechanism of underlying long-term graft survival, as
      recipient thymectomized mice were immunocompetent and harbor alloreactive T
      cells. (c) Induction of skin allograft acceptance initially depended on the
      presence of IFN-gamma, CTLA4, and CD4(+) T cells. Addition of anti-CTLA4 or anti
      IFN-gamma mAb to the protocol was associated with prompt graft rejection, whereas
      anti-IL-4 mAb had no effect. The role of IFN-gamma was confirmed using knockout
      mice. (d) Graft survival was associated with the absence of IFN-gamma in the
      graft. (e) Long-term graft maintenance required the continued presence of CD4(+)
      T cells. The results suggest that, with modification, our short-term protocol may
      yield a procedure for the induction of long-term graft survival without prolonged
      immunosuppression.

PMID- 9616217
TI  - Mobilization and homing of peripheral blood progenitors is related to reversible
      downregulation of alpha4 beta1 integrin expression and function.
AB  - Despite the wide use of mobilized peripheral blood (PB) progenitor cells (PBPC)
      for clinical transplantation the mechanism(s) underlying their mobilization and
      subsequent engraftment are still unknown. We compared the adhesive phenotype of
      CD34(+) colony-forming cells (CFC) in bone marrow (BM) and PB of normal donors
      before and after administration of granulocyte colony-stimulating factor (G-CSF)
      for 5 d. G-CSF-mobilized PB CFC cells adhered significantly less to BM stroma,
      fibronectin, and to the alpha4 beta1 binding fibronectin peptide, CS1, because of
      decreased expression of the alpha4 integrin. Since incubation of BM CD34(+) cells
      for 4 d with G-CSF at concentrations found in serum of G-CSF- treated individuals
      did not affect alpha4-dependent adhesion, G-CSF may not be directly responsible
      for the decreased alpha4-mediated adhesion of PB CFC. Culture of G-CSF-mobilized
      PB CD34(+) cells with cytokines at concentrations found in BM stromal cultures
      upregulated alpha4 expression and restored adhesion of mobilized PB CFC to
      stroma, fibronectin, and CS1. Adhesion of cultured, mobilized PB CFC to stroma
      and CS1 could not be further upregulated by the beta1 activating antibody, 8A2.
      This indicates acquisition of a maximally activated alpha4 beta1 integrin once PB
      CFC have been removed from the in vivo mobilizing milieu. Thus, decreased alpha4
      expression on CD34(+) CFC in PB may be responsible for the aberrant circulation
      of mobilized PB CD34(+) cells. Reexpression of a maximally activated alpha4 beta1
      integrin on mobilized PB CFC removed from the mobilizing in vivo milieu may
      contribute to the early engraftment of mobilized PBPC.

PMID- 9616218
TI  - Sustained pulmonary hypertension and right ventricular hypertrophy after chronic
      hypoxia in mice with congenital deficiency of nitric oxide synthase 3.
AB  - Chronic hypoxia induces pulmonary hypertension and right ventricular (RV)
      hypertrophy. Nitric oxide (NO) has been proposed to modulate the pulmonary
      vascular response to hypoxia. We investigated the effects of congenital
      deficiency of endothelial NO synthase (NOS3) on the pulmonary vascular responses
      to breathing 11% oxygen for 3-6 wk. After 3 wk of hypoxia, RV systolic pressure
      was greater in NOS3-deficient than in wild-type mice (35+/-2 vs 28+/-1 mmHg, x+/
      SE, P < 0.001). Pulmonary artery pressure (PPA) and incremental total pulmonary
      vascular resistance (RPI) were greater in NOS3-deficient than in wild-type mice
      (PPA 22+/-1 vs 19+/-1 mmHg, P < 0.05 and RPI 92+/-11 vs 55+/-5 mmHg.min.gram.ml
      1, P < 0.05). Morphometry revealed that the proportion of muscularized small
      pulmonary vessels was almost fourfold greater in NOS3-deficient mice than in wild
      type mice. After 6 wk of hypoxia, the increase of RV free wall thickness,
      measured by transesophageal echocardiography, and of RV weight/body weight ratio
      were more marked in NOS3-deficient mice than in wild-type mice (RV wall thickness
      0.67+/-0.05 vs 0.48+/-0.02 mm, P < 0.01 and RV weight/body weight ratio 2.1+/-0.2
      vs 1.6+/-0.1 mg. gram-1, P < 0.05). RV hypertrophy produced by chronic hypoxia
      was prevented by breathing 20 parts per million NO in both genotypes of mice.
      These results suggest that congenital NOS3 deficiency enhances hypoxic pulmonary
      vascular remodeling and hypertension, and RV hypertrophy, and that NO production
      by NOS3 is vital to counterbalance pulmonary vasoconstriction caused by chronic
      hypoxic stress.

PMID- 9616219
TI  - Corticotropin-releasing hormone is produced by rat corticotropes and modulates
      ACTH secretion in a paracrine/autocrine fashion.
AB  - Anterior pituitary hormone secretion is mainly regulated by hypothalamic
      releasing factors, which reach the pituitary via portal vessels. It has been
      demonstrated recently that these peptides can also be produced by the pituitary
      itself, thus possibly modulating hormone secretion in a paracrine/autocrine
      fashion. The object of this study was to seek evidence for the synthesis and
      secretion of corticotropin-releasing hormone (CRH) within the anterior pituitary
      and to ascertain its biological relevance. Messenger RNA from adult rat anterior
      pituitary fragments and cell cultures was reverse transcribed and subjected to
      PCR amplification using primers specific to the rat CRH gene. As in the
      hypothalamus, a single 232-bp band was obtained. The correspondence of the
      amplified fragment to the sequence of the CRH gene was confirmed by Southern
      blotting and restriction enzyme digestion. Combined in situ reverse transcription
      PCR amplification/immunocytochemistry demonstrated the presence of CRH mRNA in
      corticotropes. Medium from anterior pituitary primary cultures contained
      approximately 7 pg/microg protein of CRH immunoreactivity which presented the
      same chromatographic profile on HPLC as the mature CRH peptide. Incubation of
      anterior pituitary cells with an antibody directed against CRH markedly reduced
      basal ACTH secretion compared with serum-treated control wells (0.89+/-0.11 vs.
      1.74+/-0.14 ng/200,000 cells in control wells after 1 h, P < 0.05; 1.17+/-0.10
      vs. 2.16+/-0. 39 ng/200,000 cells after 2 h, P < 0.05; 1.45+/-0.12 vs. 3.12+/
      0.61 ng/200,000 cells after 3 h, P < 0.05). Further, the ACTH response to
      potassium and to forskolin was markedly blunted by the CRH antiserum as well as
      by the CRH antagonist, alpha-helical CRH(9-41). In conclusion, this study
      demonstrates the presence of CRH mRNA in normal rat corticotropes and the
      secretion of the mature peptide by the anterior pituitary, pointing to the
      production of CRH at the site of its target cells. In addition, intrapituitary
      CRH contributes in a paracrine/autocrine fashion to ACTH secretion.

PMID- 9616220
TI  - Genetic loci controlling body fat, lipoprotein metabolism, and insulin levels in
      a multifactorial mouse model.
AB  - We analyzed the inheritance of body fat, leptin levels, plasma lipoprotein
      levels, insulin levels, and related traits in an intercross between inbred mouse
      strains CAST/Ei and C57BL/6J. CAST/Ei mice are unusually lean, with only
      approximately 8% of body weight as fat, whereas C57BL/6J mice have approximately
      18% body fat. Quantitative trait locus analysis using > 200 F2 mice revealed
      highly significant loci (lod scores > 4.3) on chromosomes 2 (three separate loci)
      and 9 that contribute to mouse fat-pad mass for mice on a high-fat diet. Some
      loci also influenced plasma lipoprotein levels and insulin levels either on chow
      or high-fat diets. Two loci for body fat and lipoprotein levels (on central and
      distal chromosome 2) coincided with a locus having strong effects on hepatic
      lipase activity, an activity associated with visceral obesity and lipoprotein
      levels in humans. A locus contributing to plasma leptin levels (lod score 5.3)
      but not obesity was identified on chromosome 4, near the leptin receptor gene.
      These data identify candidate regions and candidate genes for studies of human
      obesity and diabetes, and suggest obesity is highly complex in terms of the
      number of genetic factors involved. Finally, they support the existence of
      specific genetic interactions between body fat, insulin metabolism, and
      lipoprotein metabolism.

PMID- 9616221
TI  - Inhaled NO as a viable antiadhesive therapy for ischemia/reperfusion injury of
      distal microvascular beds.
AB  - Inhaled nitric oxide (NO) is being used more and more in intensive care units as
      a modality to improve the outcome of patients with pulmonary complications. Our
      objective was to demonstrate that inhaled NO could impact upon a distally
      inflamed microvasculature-improving perfusion, leukocyte adhesive interactions,
      and endothelial dysfunction. Using intravital microscopy to visualize
      ischemia/reperfusion of postcapillary venules, we were able to demonstrate that
      the reduction in perfusion, the dramatic increase in leukocyte rolling, adhesion,
      and emigration, and the endothelial dysfunction could all be significantly
      abrogated with 80 ppm, but not 20 ppm inhaled NO. Perfusing whole blood directly
      over an inert P-selectin and CD18 ligand substratum incorporated in a flow
      chamber recruited the same number of rolling and adhering leukocytes from NO
      ventilated and non-NO-ventilated animals, suggesting that inhaled NO was not
      directly affecting leukocytes. To demonstrate that inhaled NO was actually
      reaching the peripheral microvasculature in vivo, we applied a NO synthase
      inhibitor locally to the feline mesentery and demonstrated that the
      vasoconstriction, as well as leukocyte recruitment, were essentially abolished by
      inhaled NO, suggesting that a NO-depleted peripheral microvasculature could be
      replenished with inhaled NO in vivo. Finally, inhaled NO at the same
      concentration that was effective in ischemia/reperfusion did not affect vascular
      alterations, leukocyte recruitment, and endothelial dysfunction associated with
      endotoxemia in the feline mesentery. In conclusion, our data for the first time
      demonstrate a role for inhaled NO as a therapeutic delivery system to the
      peripheral microvasculature, showing tremendous efficacy as an antiadhesive,
      antivasoconstrictive, and antipermeabilizing molecule in NO-depleted tissues, but
      not normal microvessels or vessels that have an abundance of NO (LPS-treated).
      The notion that blood borne molecules have NO carrying capacity is conceptually
      consistent with our observations.

PMID- 9616222
TI  - Oligoclonal expansion of HIV-specific cytotoxic CD8 T lymphocytes in the skin of
      HIV-1-infected patients with cutaneous pseudolymphoma.
AB  - A massive infiltration of the skin by activated CD8+ T lymphocytes involving both
      the dermis and the epidermis has been found in HIV-1-infected patients presenting
      with a chronic skin rash. We characterized the T cell receptor (TCR) BV-BJ
      junctional diversity of the skin-infiltrating lymphocytes (SILs) in four
      patients. The SILs expressed a limited set of TCRBV gene segments.
      Complementarity determining region 3 length analysis further emphasized their
      oligoclonality, suggesting that antigen stimulation might be responsible for the
      cutaneous T cell expansion. Furthermore, independent skin biopsies obtained from
      the same individual were shown to harbor distinct T cell repertoires, possibly
      reflecting the spatial heterogeneity of the antigenic stimuli. The CD8+ cytotoxic
      T lymphocyte (CTL) lines isolated from the skin rash in one patient exhibited a
      specific, class I MHC-restricted cytotoxic activity against HIV-1 Gag- and Pol
      expressing target cells, whereas CTL lines derived from the skin lesions of a
      second patient were shown to be predominantly Env-specific. Taken together, these
      data demonstrate the infiltration of HIV-specific CTLs in the skin of HIV
      infected patients, and suggest that in addition to their known role in
      controlling the retroviral infection, these CTLs may also be involved in the
      pathogenesis of cutaneous inflammatory disorders occurring during the course of
      HIV infection.

PMID- 9616223
TI  - Downregulation of T cell receptor expression by CD8(+) lymphocytes in kidney
      allografts.
AB  - Allospecific CD8(+) T lymphocytes are an important component of the cellular
      response in allograft rejection. These cells recognize and engage MHC class I
      antigens, leading to allospecific cytolytic responses and graft rejection. In
      mouse kidney allografts that survive to 3 wk after transplantation, we noted that
      the majority of CD8(+) cells do not express surface alpha/beta T cell receptor
      alpha/beta(TCR), gamma/deltaTCR, or CD3. However, these CD8(+)TCR- cells did
      express surface markers characteristic of T cells, including Thy1.2, CD2, and
      CD5. In addition, the CD8(+)TCR- cells expressed mRNA for TCR Vbeta gene
      families, and nearly half stained positive for cytoplasmic Vbeta8 protein,
      suggesting that they are T cells that have downregulated alpha/betaTCR protein
      expression from their cell surfaces. When these surface TCR- cells were isolated
      from kidney allografts by flow cytometry and cultured in the presence of either
      allogeneic or syngeneic stimulators, nearly 100% of cells reacquired normal
      levels of alpha/betaTCR expression with disproportionate usage of Vbeta8 chains.
      After recovery of their surface TCR expression, the CD8(+)TCR- population
      demonstrated strong alloreactivity in culture. These results suggest that the
      substantial number of CD8(+)TCR- cells found in long-term surviving mouse kidney
      allografts are alpha/beta-T cells that have downregulated their cell surface
      expression of TCR. While in other systems this phenotype may identify cells that
      have engaged antigen, our results indicate that loss of TCR expression by CD8(+)
      kidney graft-infiltrating cells may not depend on antigen engagement and that
      elements in the microenvironment of the kidney graft play a key role in this
      process. Factors that modulate expression of TCR by graft-infiltrating
      lymphocytes may have an important role in regulating rejection responses.

PMID- 9616224
TI  - Differential expression of the insulin gene transcriptional repressor
      CCAAT/enhancer-binding protein beta and transactivator islet duodenum homeobox-1
      in rat pancreatic beta cells during the development of diabetes mellitus.
AB  - Impairment of insulin secretion due to prolonged hyperglycemia is believed to
      contribute to the manifestation of diabetes mellitus, often referred to as
      glucose toxicity of pancreatic beta cells. In addition, impaired beta cell
      function has been associated with elevated islet triglyceride content
      (lipotoxicity). Impaired functions of the transactivating factors islet duodenum
      homeobox-1 (IDX-1) and RIPE3b-binding proteins have been implicated in the
      pathological downregulation of insulin gene transcription by high glucose levels
      in pancreatic beta cell lines in vitro, and, similarly, the exposure of
      pancreatic islets to fatty acids decreases IDX-1 expression. Previously, we
      identified the basic leucine zipper transcription factor CCAAT/enhancer-binding
      protein beta (C/ EBPbeta) as an inhibitor of insulin gene transcription in
      pancreatic beta cells and showed that the expression of C/EBPbeta is upregulated
      in insulinoma-derived beta cell lines by sustained high glucose concentrations.
      Here we describe the regulation of the expression of IDX-1, C/EBPbeta, and
      insulin at the mRNA and protein levels in pancreatic islets in animal models of
      diabetes mellitus. Concomitant with a downregulation of IDX-1 and insulin
      expression, C/EBPbeta is upregulated in association with the manifestation of
      hyperglycemia during the development of diabetes in the Zucker diabetic fatty
      (fa/fa) rat and in the 90% pancreatectomy rat model of diabetes. This regulation
      is demonstrated to influence both the amount of cellular protein and the level of
      steady state messenger RNA. Our findings indicate that the differential
      dysregulation of both IDX-1 and C/EBPbeta, in response to sustained hyperglycemia
      or hyperlipidemia, may be involved in the impairment of insulin gene expression
      during the manifestation of diabetes mellitus.

PMID- 9616226
TI  - Basal cell adhesion molecule/lutheran protein. The receptor critical for sickle
      cell adhesion to laminin.
AB  - Sickle red cells bind significant amounts of soluble laminin, whereas normal red
      cells do not. Solid phase assays demonstrate that B-CAM/LU binds laminin on
      intact sickle red cells and that red cell B-CAM/LU binds immobilized laminin,
      whereas another putative laminin binding protein, CD44, does not. Ligand blots
      also identify B-CAM/LU as the only erythrocyte membrane protein(s) that binds
      laminin. Finally, transfection of murine erythroleukemia cells with human B-CAM
      cDNA induces binding of both soluble and immobilized laminin. Thus, B-CAM/LU
      appears to be the major laminin-binding protein of sickle red cells. Previously
      reported overexpression of B-CAM/LU by epithelial cancer cells suggests that this
      protein may also serve as a laminin receptor in malignant tumors.

PMID- 9616225
TI  - Fluid shear stress activation of egr-1 transcription in cultured human
      endothelial and epithelial cells is mediated via the extracellular signal-related
      kinase 1/2 mitogen-activated protein kinase pathway.
AB  - The primary response transcription factor, early growth response-1 (Egr-1), is
      rapidly activated by a variety of extracellular stimuli. Egr-1 binds to a
      sequence found in the promoters of genes involved in vascular injury, such as
      PDGF-A and tissue factor, and trans-activates their expression in endothelial
      cells in response to fluid shear stress. Here we show that egr-1 mRNA is
      increased after 30 min of flow in human aortic endothelial cell and HeLa cell
      cultures. Transient transfection of HeLa cells with reporter gene constructs
      driven by the murine or human egr-1 5' flanking sequence revealed a five- and
      ninefold induction, respectively, in transcriptional activity after exposure to a
      shear stress of 5 dynes/cm2 for 3 h. Deletion of sequences in the murine promoter
      containing two AP1 sites and an inhibitory Egr-1 binding sequence, did not reduce
      shear stress inducibility. However, progressive deletion of five serum response
      elements, reduced both the basal promoter activity and its capacity to be
      activated by shear stress. Further examination indicated that the three upstream
      serum response elements are predominantly responsible for shear stress activation
      of the egr-1 promoter. Treatment of cells with PD98059, a specific inhibitor of
      mitogen-activated protein kinase-1 inhibited shear stress activation of egr-1. We
      suggest that egr-1 activation by shear stress involves activation of Elk-1 but
      not c-jun activity. These data, which are consistent with previous findings for
      shear mediated signaling via the mitogen-activated protein kinase cascade, now
      implicate shear modulation of the Egr-1 transcription factor in this pathway.

PMID- 9616227
TI  - Lack of strong immune selection pressure by the immunodominant, HLA-A*0201
      restricted cytotoxic T lymphocyte response in chronic human immunodeficiency
      virus-1 infection.
AB  - Despite detailed analysis of the HIV-1-specific cytotoxic T lymphocyte response
      by various groups, its relation to viral load and viral sequence variation
      remains controversial. We analyzed HLA-A*0201 restricted cytotoxic T lymphocyte
      responses in 17 HIV-1-infected individuals with viral loads ranging from < 400 to
      221,000 HIV RNA molecules per milliliter of plasma. In 13 out of 17 infected
      subjects, CTL responses against the SLYNTVATL epitope (p17 Gag; aa 77-85) were
      detectable, whereas two other HLA-A*0201 restricted epitopes (ILKEPVHGV, IV9; and
      VIYQYMDDL, VL9) were only recognized by six and five individuals out of 17
      individuals tested, respectively. Naturally occurring variants of the SL9 epitope
      were tested for binding to HLA-A*0201 and for recognition by specific T cell
      clones generated from five individuals. Although these variants were widely
      recognized, they differed by up to 10,000-fold in terms of variant peptide
      concentrations required for lysis of target cells. A comparison of viral
      sequences derived from 10 HLA-A*0201-positive individuals to sequences obtained
      from 11 HLA-A*0201-negative individuals demonstrated only weak evidence for
      immune selective pressure and thus question the in vivo efficacy of
      immunodominant CTL responses present during chronic HIV-1 infection.

PMID- 9616229
TI  - Lymphocyte apoptosis induced by Fas ligand- expressing ovarian carcinoma cells.
      Implications for altered expression of T cell receptor in tumor-associated
      lymphocytes.
AB  - We have recently reported that tumor-associated lymphocytes obtained from ascitic
      fluids of women with ovarian carcinoma (OvCA) demonstrate a marked decrease in
      expression of cytoplasmic CD3-zeta and surface CD3-epsilon chains, which is
      associated with altered function of T cell receptor (TcR). We now demonstrate
      that OvCAs in situ and in culture express functional Fas ligand (FasL), capable
      of triggering an intrinsic cell death program in Fas-expressing T cells. The
      possibility of a relationship between cell death and altered expression of TcR
      was examined. The data indicate that alterations in expression of CD3-zeta and
      CD3-epsilon chains in T cells coincubated with OvCA are related to tumor-induced
      apoptosis, as the addition of pan-caspase inhibitors, DEVD-cho or YVAD-cho,
      prevents both the in vitro induction of T cell death by OvCA cells and the
      changes in the level of expression of CD3-zeta and CD3-epsilon chains. In the
      presence of Fas-Fc fusion protein, but not Fc-control protein, the loss in
      expression of CD3-zeta and CD3-epsilon chains induced in T cells by FasL+ OvCA
      cells was prevented. These results suggest that the loss in expression of CD3
      zeta and CD3-epsilon chains in T lymphocytes interacting with OvCA cells is
      associated with apoptosis mediated by FasL-expressing tumor cells.

PMID- 9616228
TI  - Nitric oxide synthase modulates angiogenesis in response to tissue ischemia.
AB  - We tested the hypothesis that endothelial nitric oxide synthase (eNOS) modulates
      angiogenesis in two animal models in which therapeutic angiogenesis has been
      characterized as a compensatory response to tissue ischemia. We first
      administered L-arginine, previously shown to augment endogenous production of NO,
      to normal rabbits with operatively induced hindlimb ischemia. Angiogenesis in the
      ischemic hindlimb was significantly improved by dietary supplementation with L
      arginine, compared to placebo-treated controls; angiographically evident
      vascularity in the ischemic limb, hemodynamic indices of limb perfusion,
      capillary density, and vasomotor reactivity in the collateral vessel-dependent
      ischemic limb were all improved by oral L-arginine supplementation. A murine
      model of operatively induced hindlimb ischemia was used to investigate the impact
      of targeted disruption of the gene encoding for ENOS on angiogenesis.
      Angiogenesis in the ischemic hindlimb was significantly impaired in eNOS-/- mice
      versus wild-type controls evaluated by either laser Doppler flow analysis or
      capillary density measurement. Impaired angiogenesis in eNOS-/- mice was not
      improved by administration of vascular endothelial growth factor (VEGF),
      suggesting that eNOS acts downstream from VEGF. Thus, (a) eNOS is a downstream
      mediator for in vivo angiogenesis, and (b) promoting eNOS activity by L-arginine
      supplementation accelerates in vivo angiogenesis. These findings suggest that
      defective endothelial NO synthesis may limit angiogenesis in patients with
      endothelial dysfunction related to atherosclerosis, and that oral L-arginine
      supplementation constitutes a potential therapeutic strategy for accelerating
      angiogenesis in patients with advanced vascular obstruction.

PMID- 9616230
TI  - Inhibition of mesangial cell proliferation by E2F decoy oligodeoxynucleotide in
      vitro and in vivo.
AB  - The transcription factor E2F coordinately activates several cell cycle-regulatory
      genes. We attempted to inhibit the proliferation of mesangial cells in vitro and
      in vivo by inhibiting E2F activity using a 25-bp decoy oligodeoxynucleotide that
      contained consensus E2F binding site sequence (E2F-decoy) as a competitive
      inhibitor. The decoy's effect on human mesangial cell proliferation was evaluated
      by [3H]thymidine incorporation. The E2F decoy inhibited proliferation in a
      concentration-dependent manner, whereas a mismatch control oligodeoxynucleotide
      had little effect. Electrophoretic mobility shift assays demonstrated that the
      decoy's inhibitory effect was due to the binding of the decoy
      oligodeoxynucleotide to E2F. The effect of the E2F decoy was then tested in a rat
      anti-Thy 1.1 glomerulonephritis model. The E2F decoy oligodeoxynucleotide was
      introduced into the left kidney 36 h after the induction of glomerulonephritis.
      The administration of E2F decoy suppressed the proliferation of mesangial cells
      by 71%. Furthermore, treatment with the E2F decoy inhibited the glomerular
      expression of proliferating cell nuclear antigen at the protein level as well as
      the mRNA level. These findings indicate that decoy oligonucleotides can suppress
      the activity of the transcription factor E2F, and may thus have a potential in
      treating glomerulonephritis.

PMID- 9616232
TI  - Chiropractors' use of X-rays.

PMID- 9616231
TI  - Activation of NF-kappaB by adherent Pseudomonas aeruginosa in normal and cystic
      fibrosis respiratory epithelial cells.
AB  - PMN-dominated airway inflammation is a major component of cystic fibrosis (CF)
      lung disease. Epithelial cells respond to organisms such as Pseudomonas
      aeruginosa, the major pathogen in CF, by expressing the leukocyte chemokine IL-8.
      Experiments were performed using several different types of respiratory
      epithelial cells that demonstrate that ligation of ceramide-associated receptors
      on epithelial surfaces by P. aeruginosa pili is a major stimulus for the
      translocation of transcription factor nuclear factor (NF)-kappaB and initiation
      of IL-8 expression by epithelial cells. Using electrophoretic mobility shift
      assays and Western hybridizations, nuclear NF-kappaB was found shortly after
      epithelial cells were stimulated by either whole organisms, isolated pili, or
      antibody to the pilin receptor asialoGM1. IB3 cells, which express mutations in
      cystic fibrosis transmembrane conductance regulator (CFTR) (DeltaF508/W1282X),
      were noted to have significantly greater amounts of endogenous nuclear NF-kappaB,
      but not the transcription factor C/EBP, than CF cells corrected by episomal
      copies of normal CFTR (C-38) or IB3 cells grown at a permissive temperature (25
      degreesC). Activation of NF-kappaB and subsequent IL-8 expression in epithelial
      cells can result from activation of at least two pathways: an exogenous signaling
      cascade that is activated by ligation of ceramide-associated adhesins such as P.
      aeruginosa pilin, or endogenous stimulation, suggested to be a consequence of
      cell stress caused by the accumulation of mutant CFTR in the endoplasmic
      reticulum.

PMID- 9616233
TI  - The use of nuclear medicine in infections.
AB  - The spectrum of infectious diseases has changed over the last few years, hence
      the requirements for radionuclide imaging for the detection of infection are
      becoming more demanding so that, although gallium-67 and labelled leucocytes
      remain useful agents, there is currently great interest in the development of new
      agents especially able to target chronic, non-pyogenic inflammation. Agents can
      be classified according to the site at which the radiolabel is targeted: pre
      endothelial (for example, labelled leucocytes), endothelial (for example,
      labelled anti-endothelial monoclonal antibodies) or post-endothelial (for
      example, fluorine-18-fluorodeoxyglucose (FDG)). 67Ga and labelled polyclonal
      human immunoglobulin (HIG) localize at inflammation initially as a result of
      increased endothelial permeability, followed by retention of the label through
      binding to local extravascular receptors. Labelled leucocytes are avidly taken up
      by acute pyogenic inflammatory foci but perform less well in chronic
      inflammation. Other indications for labelled leucocytes include bone infection
      and undiagnosed fever. Nevertheless, since many causes of the latter do not
      stimulate a neutrophilic infiltrate, a non-specific agent, such as 67Ga, FDG or
      HIG, may be preferable, especially in patients with no immediate significant
      medical history. Since endothelial E-selectin expression is closely correlated to
      lymphocyte migration, labelled anti-E-selectin monoclonal antibody may also have
      a potential role for imaging chronic inflammation.

PMID- 9616234
TI  - Virtual cystoscopy based on helical CT scan datasets: perspectives and
      limitations.
AB  - The purpose of the study was to simulate cystoscopy based on three-dimensional
      helical CT scan datasets in real-time in patients with tumours of the urinary
      bladder. A helical CT scan with double detector technology was carried out pre
      operatively in 11 patients with histologically confirmed carcinoma of the urinary
      bladder and one patient with chronic cystitis. A non-enhanced scan was first
      performed, followed by an examination in the early phase of contrast medium
      enhancement. Further images were acquired after adequate filling of the bladder
      with contrast medium, approximately 30 min after injection. These data were
      transferred to a separate graphic computer workstation and reconstructed. The
      results were then compared with the cystoscopic and histopathological findings.
      All tumours of the urinary bladder identified at fibreoptic cystoscopy were shown
      on virtual cystoscopy. The best reconstruction results were obtained from data
      acquired 30 min after injection of contrast medium. The ureteric orifices were
      not visualized at virtual cystoscopy. These data lead us to conclude that, at
      present, virtual cystoscopy has not reached the quality of fibreoptic examination
      and remains restricted to use in specific cases, for example patients with
      urethral strictures.

PMID- 9616235
TI  - Three-dimensional spiral CT angiography in pancreatic surgical planning using non
      tailored protocols: comparison with conventional angiography.
AB  - The aim of this study was to investigate three-dimensional spiral computed
      tomography (3DCT) as an adjunct to routine pancreatic CT scanning, with
      particular regard to the identification of surgically important hepatic arterial
      anomalies, correlated with conventional visceral angiography. 32 patients
      underwent spiral CT scans prior to pancreatic surgery using established
      protocols. Oral contrast medium was used throughout. 150 ml of intravenous
      contrast medium was given at 3 ml s-1 with a 24 s spiral CT sequence starting 35
      s after the start of infusion. Two protocols were employed, both with a pitch of
      1:3 mm table feed/collimation (n = 17) and 5 mm table feed/collimation (n = 15).
      Overlapping (1 mm minimum) axial reformats were reconstructed. 3DCT shaded
      surface displays of the visceral arteries were assessed for visceral arterial
      anomalies. Visceral angiography (n = 23) was independently correlated.
      Satisfactory 3D angiograms were performed in all but one patient, in whom the
      coeliac axis was missed. (i) 3 mm protocol: 3DCT (n = 17) showed three anomalous
      right hepatic arteries (ARHA), one trifurcation anomaly and one splenic artery
      with an aortic origin. Angiography (n = 11) confirmed these findings, although
      one patient with an ARHA did not have angiography. A left gastric arterial supply
      to the left liver was not detected. (ii) 5 mm protocol: 3DCT (n = 15) showed two
      cases of ARHA. While confirming these findings, angiography (n = 12) showed a
      third case of ARHA, in which the coeliac and superior mesenteric artery had very
      close origins. A left gastric supply to the left liver was also missed. It is
      concluded that satisfactory 3DCT is possible without changing existing scanning
      protocols, although narrow sections are required for the confident assessment of
      right hepatic arterial anomalies, and any left hepatic supply via the left
      gastric artery was poorly assessed in this series.

PMID- 9616236
TI  - In vivo assessment of neovascularization of liver metastases using perfusion CT.
AB  - Neovascularization of tumours produces a high microvessel density. Although
      diagnostic imaging is unable to visualize microvessels directly, it is possible
      to demonstrate associated changes in tissue perfusion. The aim of this study was
      to use the quantitative functional information and high spatial resolution of
      perfusion computed tomography to study neovascularization of hepatic metastases.
      Perfusion CT was performed in 13 patients with hepatic metastases from various
      primary tumours. Arterial perfusion was measured in the metastasis; both arterial
      and portal perfusion were measured in a small rim of liver tissue immediately
      adjacent to the metastasis. Perfusion measurements were correlated against
      survival of the patient in nine cases. Arterial perfusion was increased above
      normal values, both in the metastasis (median: 0.62 ml min-1 ml-1; range: 0.26
      3.05 ml min-1 ml-1) and in the adjacent liver (median: 0.51 ml min-1 ml-1; range:
      0.14-1.60 ml min-1 ml-1). Portal perfusion of adjacent liver was highly variable
      (median: 0.30 ml min-1 ml-1; range: 0.05-1.85 ml min-1 ml-1). Arterial perfusion
      was positively correlated with portal perfusion within liver tissue adjacent to
      metastases (p < 0.05, r = 0.58), a reversal of the normal situation. Survival of
      the patient correlated with arterial perfusion within the metastasis (p < 0.05, r
      = 0.69) but more closely with arterial perfusion in the adjacent liver (p < 0.02,
      r = 0.78). In conclusion, alterations in perfusion within metastases and adjacent
      liver are in accordance with the histological features of neovascularization.
      Perfusion CT offers a method for studying neovascularization in the living
      patient and offers prognostic information.

PMID- 9616237
TI  - Use of fluid-attenuated inversion recovery (FLAIR) pulse sequences in perinatal
      hypoxic-ischaemic encephalopathy.
AB  - The purpose of this study was to evaluate the usefulness of fluid-attenuated
      inversion recovery (FLAIR) techniques in patients with perinatal hypoxic
      ischaemic encephalopathy. 13 patients with a history of perinatal hypoxic
      ischaemic encephalopathy (age range 1 month to 3.6 years) underwent T1 and T2
      weighted spin echo and FLAIR imaging with a 1.5 T superconducting unit. FLAIR
      images were qualitatively evaluated in comparison with T1 and T2 weighted images
      by three experienced radiologists. Quantitative analysis (contrast and contrast
      to-noise ratio) was also performed. FLAIR images were preferred to T1 and T2
      weighted images in the demonstration of periventricular leukomalacia (PVL),
      cystic PVL and subcortical lesions near the brain surface. On T1 and T2 weighted
      images, almost all lesions were demonstrated as hypointense or hyperintense
      areas, respectively. However, FLAIR images could differentiate cystic lesions by
      their signal intensities. FLAIR images were not diagnostic in two cases with PVL.
      In conclusion FLAIR sequences provide useful information in patients with
      perinatal hypoxic-ischaemic encephalopathy.

PMID- 9616238
TI  - Comparison of MR sequences in quantifying in vitro cartilage degeneration in
      osteoarthritis of the knee.
AB  - Magnetic resonance imaging of amputated human knees was performed to determine
      optimal sequences for depicting articular cartilage. 24 knees were examined with
      eight different sequences in a 1.0 T imager. Each cartilage lesion was graded
      from 1 to 4 (Outerbridge staging system). The results of each sequence were
      compared with the macroscopic findings and statistically tested against each
      other. The FLASH sequence (TR = 50 ms) with combination of flip angle of 40
      degrees and echo time of 10 ms and the FISP sequence (TR = 40 ms) with
      combination of flip angle of 40 degrees and echo time of 11 ms were best for
      depicting cartilage structure and internal detail. There was no significant
      difference between fat-saturated three-dimensional FLASH (FS-3D-FLASH) and FS-3D
      FISP (p = 0.05). These FS-3D sequences were significantly better than sequences
      without fat saturation (p = 0.05). There was no significant difference between
      magnetization transfer (MT) 3D-FLASH, MT-3D-FISP and 3D-FISP. All 3D sequences
      showed significantly (p = 0.05) better results than spin echo or fast spin echo
      sequences. The T1 weighted SE pulse sequence was significantly (p = 0.005) better
      than the T2 weighted TSE sequence. Fast T2 weighted spin echo was not suitable
      for early and accurate detection of cartilage lesions.

PMID- 9616239
TI  - Studies of acoustic streaming in biological fluids with an ultrasound Doppler
      technique.
AB  - Acoustic streaming generated by diagnostic ultrasound fields is an important area
      for study both for safety reasons and because of its potential application as a
      diagnostic tool. A method of investigating streaming in biological fluids is
      reported. A number of fluids were insonated using a 3.5 MHz weakly focused single
      element transducer which was driven in pulsed mode. Streaming was detected in
      each fluid using an 8 MHz continuous wave Doppler system. The maximum streaming
      velocity was obtained by spectral analysis of the Doppler signal. Using this
      system longitudinal streaming profiles were measured. At an acoustic power of 150
      mW the maximum streaming velocities detected were: 9.3 cm s-1 in water, 6.8 cm s
      1 in 4.5% human serum albumin (HSA) solution and 4.9 cm s-1 in blood, when
      transmission was through a water path of approximately 10 cm into a 3 cm sample
      of fluid. When measurements were made in the biological fluids alone, without a
      water path, the maximum streaming velocities were reduced.

PMID- 9616240
TI  - The secondary radiation grid; its effect on fluoroscopic dose-area product during
      barium enema examinations.
AB  - The secondary radiation grid is placed between the patient and the image
      intensifying screen, during fluoroscopy, to attenuate the incident forward
      scattered radiation. This reduction in scatter improves the radiographic contrast
      and hence image quality. However, this improved quality is achieved at the
      expense of greater radiation exposure to the patient, as this higher exposure is
      required to produce satisfactory image density. Patients scheduled to have a
      barium enema were randomly allocated into two groups. One group had the procedure
      performed with the grid in situ throughout the procedure. The second group was
      examined with the grid removed for fluoroscopy but returned for image
      acquisition. The fluoroscopic dose-area product (DAP) was recorded for both
      groups using a dose-area product meter. The DAP was not recorded for spot film
      acquisition. The results suggest that there is approximately a 50% reduction in
      DAP to the second group. We can be 95% certain that, on average, the ratio of
      doses in patients without the grid in situ to those screened with the grid is
      between 0.40 and 0.58, with the best estimate being 0.48. Multiple regression
      methods to take account of the effects of weight, sex and time, revised this
      estimate as 0.57, with 95% confidence interval from 0.52 to 0.63. Sex, weight and
      exposure time accounted for 61% of variation in dose-area products, with time
      alone accounting for 41%. Grid status accounted for another 22% of variation,
      which represents over a half of the remaining variation once sex, weight and
      exposure time have been allowed for. We therefore recommend that the routine use
      of an antiscatter grid during fluoroscopy should be abandoned. The use of a grid
      should be restricted to those patients (usually obese) when poor visualization is
      obtained in its absence.

PMID- 9616241
TI  - The effects of radioactive iodine in thyroid remnant ablation and treatment of
      well differentiated thyroid carcinoma.
AB  - Although the use of radioactive iodine (131I) in the treatment of thyroid cancer
      is well established, treatment dose is not well standardized. In order to deduce
      the appropriate dose for thyroid remnant ablation and the effect of 131I in the
      treatment of distant metastases, data for 544 patients with papillary or
      follicular thyroid cancer were retrospectively reviewed. All patients received
      surgical treatment followed by post-operative 131I. If remnants were present in
      the 0.2 GBq 131I diagnostic scan, 1.1-3.7 GBq 131I were administered for
      ablation. For the treatment of distant metastases 3.7-5.6 GBq were used. Of 318
      patients receiving 131I for thyroid remnant ablation, 290 were successfully
      ablated. After one dose of 1.1 GBq 131I, 82% (159/194) of thyroid remnants were
      ablated. During the follow-up period, two of 14 Stage IV patients with lung or
      mediastinal metastases at the time of operation achieved complete clinical
      remission. Factors identified as influencing response to 131I therapy included
      age, clinical stage, survival, recurrence, extent of surgery and the 1 month post
      operative serum thyroglobulin (Tg) level. In conclusion 1.1 GBq 131I was adequate
      for thyroid remnant ablation unless distant metastases were present. Radioactive
      131I has a role in the treatment of well differentiated thyroid carcinoma with
      pulmonary metastases but seems to be less effective for treatment of bone
      metastases.

PMID- 9616242
TI  - Comparison of radiation dose from intravenous urography and 99Tcm DMSA
      scintigraphy in children.
AB  - Intravenous urography (i.v.u.) and 99Tcm DMSA scintigraphy are possible
      alternative diagnostic techniques in paediatric renal investigation. Radiation
      dose comparisons between them have been complicated in the past by the lack of
      paediatric data. In this study, evaluations relevant to children are used to
      compare estimates of effective dose from the two techniques. For the radiographic
      procedures, standard operating parameters and representative age-dependent values
      of entrance surface dose were established from recent literature. Conversion
      factors relating effective dose to entrance surface dose and dose-area product
      are presented and used to obtain values of effective dose for single radiographs
      of abdomen, kidneys and pelvis. Suggested i.v.u. procedures consisting of four
      ("minimum") or eight ("average") radiographs were adopted to derive the effective
      dose for full i.v.u. examinations. 99Tcm DMSA dose estimates, taken from our
      published work using an administered activity schedule based on body surface
      area, are almost constant at about 1 mSv for all children. In comparison, mean
      i.v.u. doses based on the "average" number of radiographs are similar to DMSA
      doses for infants (< 1 year) but may be twice as high for older children.
      Although the differences between procedures at this level of dose do not in
      themselves provide grounds for preference, when coupled with the lower diagnostic
      sensitivity of i.v.u. they suggest limitations of this procedure for detection of
      a renal scar.

PMID- 9616243
TI  - Selective delivery of 10B to soft tissue sarcoma using 10B-L-borophenylalanine
      for boron neutron capture therapy.
AB  - Boron neutron capture therapy (BNCT) may improve the locoregional control of
      radio/chemoresistant tumours like soft tissues sarcomas (STS). This technique
      uses the 10B(n,alpha)7Li nuclear reaction to destroy tumour cells, provided that
      a sufficient amount of 10B may be carried selectively into them. In order to
      evaluate the targeting potential of 10B-L-borophenylalanine (BPA) a 10B
      biodistribution study was carried out in 24 Wistar rats bearing Yoshida sarcoma.
      Six animals received increasing intraperitoneal doses of BPA (300, 600 and 1200
      mg kg-1), while the remainder received a BPA dose of 600 mg kg-1 but with a
      sacrifice at six different time points: 1, 2, 4, 6, 9 and 12 h. The 10B
      concentrations in the tumours, normal tissues and blood were analysed with
      neutron capture radiography (NCR). The analysis shows that 36 micrograms g-1 (+/-
      4 SD) of 10B may be incorporated into the tumour, with a ratio of 13 (+/- 4 SD)
      versus the muscle and a ratio of 15 (+/- 3 SD) versus the blood, 6 h after an
      intraperitoneal injection of 600 mg kg-1 of BPA. The BPA appears to be abundantly
      incorporated in the tumour, and the kidney proximal tubule area. These data
      suggest that BNCT using BPA may provide an improved therapeutic ratio for the
      treatment of STS.

PMID- 9616244
TI  - The ultrasound appearances of intratesticular varicocoele.
AB  - Extratesticular varicocoele is a common clinical finding, with well recognized
      sonographic appearances. We report the ultrasound findings in a patient with
      intratesticular varicocoele (ITV), an extremely rare entity, which was an
      incidental finding during scrotal sonography. There are differences in both the
      imaging findings and clinical presentation from previously reported cases. The
      history of undescended testis and subsequent orchidopexy in our patient
      contribute to the aetiology of the ITV.

PMID- 9616245
TI  - An unusual form of pneumatosis intestinalis associated with appendicitis.
AB  - A rare case of pneumatosis intestinalis is described in a patient with
      appendicitis. Gas in the colonic wall, epiploic appendices and mesentery caused a
      new appearance not previously reported on plain radiography or CT. The relevance
      of an associated redundant right colon is also discussed.

PMID- 9616246
TI  - Cervical ecchordosis physaliphora: CT and MR features.
AB  - We report a case of cervical ecchordosis physaliphora in an elderly man who
      presented with hemihypoaesthesia and contralateral hemiparesis. MRI showed a well
      defined, non-enhancing extradural mass lesion on the dorsal surface of the
      odontoid process of the axis. The lesion was of intermediate signal intensity on
      T1 weighted images and of low signal intensity on T2 weighted images. CT showed a
      small bony defect on the adjacent cortex of the odontoid process. Recognition of
      the imaging features of ecchordosis physaliphora is helpful in suggesting the
      diagnosis and differentiating the lesion from chordoma.

PMID- 9616247
TI  - Giant fusiform basilar artery aneurysm: endovascular treatment by flow reversal
      in the basilar artery.
AB  - We report a patient presenting with subarachnoid haemorrhage due to rupture of a
      giant fusiform aneurysm of the proximal basilar artery. The aneurysm was
      successfully treated by reversing blood flow in the basilar artery by balloon
      occlusions of both vertebral arteries proximal to the posterior inferior
      cerebellar artery origins. Substantial thrombosis and regression of the aneurysm
      was evident 4 months later.

PMID- 9616248
TI  - Metastatic cardiac osteosarcoma--imaging features.
AB  - There are several reports of osteosarcoma metastases to the heart. A rare case of
      a metastatic osteosarcoma to the endocardium of the left atrium in a 17 year old
      patient is described. The radiological features are discussed in detail.

PMID- 9616249
TI  - Appearances of paranasal fungal sinusitis on computed tomography.
AB  - The primary invasive granulomatous form of fungal sinusitis, due to inhalation of
      aspergillus spores, is commonest in the Sudan and the Gulf states. This condition
      often presents clinically as a chronic, severe sinusitis which has not responded
      to antibiotics. On CT scanning, the major feature is a soft tissue mass, which is
      either homogeneous or has lower attenuation components. There may be erosion or
      expansion of the bony margins of the sinuses. Intraorbital and/or intracranial
      extension sometimes occur.

PMID- 9616250
TI  - Not another episode of loin pain!

PMID- 9616251
TI  - Aneurysm of the left brachiocephalic vein: an unusual cause of mediastinal
      widening.

PMID- 9616252
TI  - Clinicians interpretation of the indeterminate ventilation-perfusion scan report.

PMID- 9616253
TI  - Glaxo/MRS Young Investigator Medal. Molecular studies on adenosine deaminase
      deficiency and hereditary haemorrhagic telangiectasia.
AB  - 1. This manuscript describes two different strategies to progress from the
      clinical assessment of patients to the identification of disease-causing
      mutations. In the first disease, recognition of a metabolic abnormality allowed
      direct molecular analysis of the causal gene. In contrast, localization of the
      second disease gene by linkage analysis was critical to implicate a gene with a
      previously unsuspected disease role. 2. Two sisters with chronic respiratory
      disease and recurrent infections were identified as the first cases of adult
      onset immunodeficiency due to adenosine deaminase deficiency. Autosomal recessive
      inheritance of two mutations in the adenosine deaminase gene was demonstrated.
      Enzyme replacement therapy improved the patients' immunological and clinical
      status. 3. Individuals with pulmonary arteriovenous malformations were used to
      identify families with hereditary haemorrhagic telangiectasia (HHT, Rendu-Osler
      Weber Syndrome). Linkage studies mapped the HHT disease gene in some families to
      chromosome 9, and demonstrated genetic heterogeneity. The chromosome 9 disease
      interval was refined, and several candidate genes were assessed. Following the
      first description of disease-segregating mutations, a complete analysis of the
      endoglin gene (which encodes an endothelial cell transforming growth factor-beta
      receptor) identified seven novel mutations. Two mutations did not produce mutant
      mRNA, and disease severity was comparable between families, indicating that HHT
      results from stoichiometric insufficiency of endoglin. 4. Each study has
      implications extending beyond the relatively rare disease analysed. The adenosine
      deaminase-deficient patients highlight a treatable cause of HIV-negative CD4+
      lymphopenia in adults, perhaps accounting for further cases of 'non-HIV AIDS'.
      The HHT studies have illuminated a novel area of vascular pathophysiology, with
      potential relevance to further disease states.

PMID- 9616254
TI  - Epidermal growth factor protects against carbon tetrachloride-induced hepatic
      injury.
AB  - 1. Epidermal growth factor (EGF) is known to protect the gastrointestinal tract
      against various noxious agents. Its potential value in preventing/ treating
      hepatic injury is, however, largely unexplored. We therefore examined whether EGF
      could influence CCl4-induced hepatic injury. 2. Female Sprague-Dawley rats (8 per
      group) received saline or recombinant EGF (500 or 750 micrograms/kg,
      intraperitoneal) 30 min before CCl4 (20% v/v, in olive oil, intraperitoneal).
      Eighteen hours later, animals were killed, serum was collected for assay of
      biochemical markers of hepatic injury and livers were removed for histological
      analyses. 3. Administration of CCl4 resulted in severe hepatic necrosis and
      caused a 10-fold rise in plasma alanine aminotransferase levels compared with
      levels seen in control animals (218 +/- 15 compared with 23 +/- 9 mumol/l in
      controls, mean +/- SEM, P < 0.01). Serum malondialdehyde levels, used as a marker
      of lipid peroxidation, showed a 2-fold rise in response to CCl4 treatment (median
      4.0, quartile range 3.3-5.8 units/l compared with median 2.3, quartile range 2.1
      2.5 units/l in controls, P < 0.05). Administration of EGF at 500 micrograms/kg,
      before the CCl4, did not protect against injury, as assessed by histology or rise
      in plasma alanine aminotransferase levels. In contrast, animals given EGF at 750
      micrograms/kg, before the CCl4, had only minimal changes in histology, with only
      a minor rise in alanine aminotransferase levels (37 +/- 4 compared with 23 +/- 9
      mumol/l in animals not given CCl4) and had no significant rise in malondialdehyde
      levels. 4. EGF protects against CCl4-induced hepatic injury and may provide a
      novel approach to the treatment of liver damage.

PMID- 9616255
TI  - Nitric oxide modulation of coronary artery myogenic tone in spontaneously
      hypertensive and Wistar-Kyoto rats.
AB  - 1. The endothelium contributes substantially to the modulation of myogenic tone
      in coronary arteries from spontaneously hypertensive rats (SHR) and Wistar-Kyoto
      rats (WKY). This study has addressed the contributions of endothelium-derived
      nitric oxide and cyclo-oxygenase products to this modulation in small coronary
      arteries (approximately 200 microns internal diameter) from 20-week-old SHR and
      WKY under pressurized, no-flow conditions in an arteriograph. 2. Active pressure
      diameter relationships were uninfluenced by the cyclo-oxygenase inhibitor
      indomethacin (10 mumol/l) in either rat strain. In the presence of indomethacin
      and the nitric oxide synthase inhibitor N omega-nitro-L-arginine (L-NNA, 0.1
      mmol/l), coronary arteries from SHR and WKY generated significantly greater
      myogenic tone. This increase in tone was similar in both strains. 3. In
      endothelium-denuded arteries, indomethacin and L-NNA did not influence tone. 4.
      Therefore, these results demonstrate that endothelium-derived nitric oxide is
      basally released to attenuate SHR and WKY coronary artery myogenic tone, whereas
      endothelium-derived cyclo-oxygenase products have no net vasoactive influence.
      Additionally, these data suggest that basal nitric oxide-mediated relaxation is
      normal in SHR coronary arteries and is therefore unlikely to be a pathogenic
      mechanism in this animal model of hypertension.

PMID- 9616256
TI  - Influence of mode of contraction on the mechanism of acetylcholine-mediated
      relaxation of coronary arteries from normotensive and spontaneously hypertensive
      rats.
AB  - 1. Endothelium-dependent acetylcholine-mediated relaxations of small coronary
      arteries (approximately 200 microns internal diameter) from 20 weeks old
      spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY)
      controls were compared under pressurized no-flow conditions after the development
      of myogenic tone or constriction with the thromboxane A2 mimetic U46619. 2.
      Relaxations of WKY and SHR arteries following development of myogenic tone did
      not differ and were not significantly influenced by indomethacin alone (10
      mumol/l) or in combination with N omega-nitro-L-arginine (L-NNA, 0.1 mmol/l).
      Maximum relaxations were significantly attenuated by 30 mmol/l K+ in the SHR,
      from 85 +/- 7% (n = 11) to 20 +/- 8% (n = 8), P < 0.001, and in the WKY from 86
      +/- 5% (n = 9) to 39 +/- 14% (n = 8), P < 0.01. 3. Relaxations following
      constriction with U46619 were also similar in both rat strains. Maximum
      relaxations were 50 +/- 11% (n = 8) in SHR and 60 +/- 7% (n = 6) in WKY.
      Indomethacin did not influence these relaxations. The combination of indomethacin
      and L-NNA attenuated relaxations in WKY (P < 0.01), but in the SHR the
      attenuation did not achieve statistical significance (P = 0.07) compared with
      controls; the maximum responses were reduced to 25 +/- 7% (n = 8) and 14 +/- 11%
      (n = 6) in the SHR and WKY respectively, but only in the WKY was this reduction
      significant (P < 0.05). 4. These data demonstrate that, under control conditions,
      SHR and WKY coronary arteries relax equally effectively, regardless of mode of
      contraction, and also that the mechanism of acetylcholine-mediated relaxation
      differs according to the mode of contraction. Acetylcholine relaxes myogenic tone
      by a K(+)-sensitive mechanism in both WKY and SHR, consistent with a role for
      endothelium-derived hyperpolarizing factor; NO contributes substantially to the
      relaxation of U46619-induced tone by acetylcholine in the WKY, but to a
      diminished extent in the SHR. 5. These data indicate that the choice of
      vasoconstrictor agent is of critical concern when assessing mechanisms of
      endothelium-dependent relaxation and abnormalities thereof in hypertension.

PMID- 9616257
TI  - Non-invasive investigation of endothelium-dependent dilatation of the brachial
      artery in women with primary Raynaud's phenomenon.
AB  - 1. Primary Raynaud's phenomenon is characterized by white fingers and toes with
      impaired perfusion in response to cold or emotional stress. The aetiology has not
      been clarified. In previous studies we have demonstrated a season-linked
      inability in women with primary Raynaud's phenomenon to raise their plasma cGMP
      levels in response to whole-body cooling, suggesting a dysfunction of the L
      arginine-NO-cGMP pathway. To further elucidate the possibility of such a defect
      in patients with primary Raynaud's phenomenon, we determined flow-mediated
      dilatation of the brachial artery. 2. Twenty-two premenopausal, non-smoking women
      with primary Raynaud's phenomenon (mean age 39 +/- 8 years) and 23 healthy
      controls (mean age 41 +/- 7 years) were studied during two winter weeks. The
      diameter of the right arm brachial artery was measured by high resolution
      ultrasonography, at rest and during reactive hyperaemia. The investigation was
      conducted both with the participants at rest at room temperature and after 40 min
      of whole-body cooling. 3. Both study groups showed a marked attenuation of flow
      mediated dilatation during whole-body cooling, which could partly but not solely
      be explained by a decreased shear rate. There was, however, no significant
      difference in flow-mediated diameter (D) increase (% flow-mediated dilatation;
      delta D/D x 100) between primary Raynaud's phenomenon and controls, either at
      room temperature (7.8 +/- 0.8 and 9.0 +/- 0.8) or in response to whole-body
      cooling (3.8 +/- 1.2 and 4.4 +/- 0.7). 4. Thus, whole-body cooling markedly
      impairs flow-mediated dilatation in women. Flow-mediated dilatation is, however,
      not decreased in women with primary Raynaud's phenomenon at room temperature or
      during whole-body cooling, indicating that this particular aspect of endothelial
      function is not impaired in this setting.

PMID- 9616258
TI  - Applicability of new techniques in the assessment of arterial baroreflex
      sensitivity in the elderly: a comparison with established pharmacological
      methods.
AB  - 1. There has been considerable interest in techniques recently developed for the
      study of arterial baroreceptor-cardiac reflex sensitivity based on analysis of
      spontaneous baroreflex sequences and on spectral analysis. This study examined
      how these newer techniques agreed with the established pharmacological methods in
      elderly subjects. 2. In 20 elderly subjects [10 hypertensive (clinic blood
      pressure 180 +/- 4/88 +/- 2 mmHg) and 10 normotensive (clinic blood pressure 136
      +/- 3/73 +/- 2 mmHg)], we assessed baroreflex sensitivity from spontaneous
      sequences of increasing and decreasing blood pressure and pulse interval and
      their mean, and from spectral analysis to derive alpha, the index of overall
      baroreflex gain. Pharmacological baroreflex sensitivity was derived from the
      blood pressure and pulse interval responses to depressor (sodium nitroprusside)
      and pressor (phenylephrine) stimuli, and their mean. 3. Baroreflex sensitivity
      was significantly lower in the hypertensive group by the pharmacological,
      sequence and spectral methods (all P < 0.05). 4. There was acceptable agreement
      between pharmacological baroreflex sensitivity and sequences of the same
      direction, but with some systematic bias. There was also reasonable agreement
      between pharmacological and spectral baroreflex sensitivity and close agreement
      without bias between sequence and spectral methods. 5. The newer and established
      techniques demonstrate acceptable agreement in the elderly, albeit with some
      systematic bias. Pharmacological methods have enjoyed historical precedence but
      newer techniques give equivalent results, and are preferable in some
      circumstances. The newer techniques may be more descriptive of the spontaneous
      behaviour of the arterial baroreflex at rest rather than under artificially
      stimulated conditions.

PMID- 9616259
TI  - Skin microcirculation in patients with type I diabetes with and without
      neuropathy after neurovascular stimulation.
AB  - 1. Neurovascular inflammation is impaired in patients suffering from diabetic
      neuropathy. The aim of our study was to evaluate the distribution of nutritive
      and total skin blood flow in diabetic patients with and without neuropathy after
      neurovascular stimulation with acetylcholine. 2. Twenty patients with Type I
      diabetes, 10 with and 10 without neuropathy, and 10 age-matched non-diabetic
      control subjects, underwent microvascular investigations before and after
      neurovascular stimulation by intracutaneous application of acetylcholine. The
      capillary blood cell velocity in the nailfold of the hallux was measured by
      videophotometric capillaroscopy, and the total skin microcirculation in the same
      area by laser Doppler flowmetry. 3. The increase in total skin blood flow was
      significantly impaired in the group of neuropathic diabetic patients compared
      with the non-neuropathic diabetic patients (17.5 +/- 8.3 versus 51.0 +/- 16.2; P
      < 0.05) and the non-diabetic subjects (17.5 +/- 8.3 versus 67.8 +/- 19.7; P <
      0.01). The increase in capillary blood flow was not significantly impaired in
      Type I diabetes patients with neuropathy. 4. The ratio between capillary blood
      flow and total skin perfusion decreased significantly in the control group (from
      0.82 +/- 0.15 to 0.47 +/- 0.11; P < 0.05) and in the Type I diabetes patients
      without neuropathy (from 0.79 +/- 0.12 to 0.43 +/- 0.12; P < 0.05), whereas the
      decrease in the neuropathic group was statistically insignificant (from 1.05 +/-
      0.19 to 0.72 +/- 0.16). 5. Diminished total skin perfusion in the foot after
      intracutaneous stimulation with acetylcholine in Type I diabetes patients is
      associated with diabetic neuropathy, indicating a disturbance in the
      neurovascular reflex arc. This impaired neurovascular response is caused by a
      diminished total and subpapillary blood flow and not by a diminished nutritive
      capillary flow. There is no evidence of a diminished nutritive capillary blood
      flow during neurogenic inflammation in Type I diabetes patients suffering from
      diabetic neuropathy.

PMID- 9616260
TI  - Autoimmune and clinical characteristics of type I diabetes in children with
      different genetic risk loads defined by HLA-DQB1 alleles. Childhood Diabetes in
      Finland Study Group.
AB  - 1. The impact of different genetic risk loads defined by HLA-DQB1 alleles on the
      autoimmune and clinical characteristics of 647 children and adolescents with
      recent-onset Type I diabetes was evaluated in a prospective population-based
      study. The subjects were divided into four groups based on HLA-DQB1 genotypes:
      DQB1*0302/0201 (high risk), *0302/x (moderate risk), *0201/y (low risk) and *z/z
      (decreased risk). 2. Close to two thirds (62.3%) of the subjects possessed a high
      or moderate risk genotype. A decreased frequency of positivity for islet cell
      antibodies (ICA) and insulin autoantibodies (IAA) (76.8% compared with 85.3%; P =
      0.05, and 30.5% compared with 50.8%, P = 0.0006, respectively) but not of
      positivity for antibodies to the 65 kDa isoform of glutamate decarboxylase was
      observed in children with the DQB1*0201/y genotype compared with other children.
      Among ICA-negative subjects, those with the DQB1*0201/y genotype had higher serum
      C-peptide levels over the first 2 years after the diagnosis of Type I diabetes
      than those with other genotypes (P = 0.028). 3. Our data provide some evidence of
      HLA-DQB1-determined heterogeneity in the autoimmune and clinical characteristics
      of childhood Type I diabetes at the time of the clinical manifestation. This
      suggests differences between children with various HLA-DQB1 genotypes in the pace
      and/or intensity of the beta-cell destructive process leading to clinical Type I
      diabetes.

PMID- 9616261
TI  - Function of rat skeletal muscles after storage at 10 degrees C in various
      preservation solutions.
AB  - 1. The purpose of this study was to assess the potential of various preservation
      solutions, orginally designed for solid organs, to protect muscle function during
      cold storage. 2. The soleus (SOL) and the cutaneous trunci (CT) muscle from the
      rat were isolated and stored for 2, 4 or 8 h at 10 degrees C. The solutions used,
      listed in order from an intracellular to an extracellular-like composition, were:
      University of Wisconsin (UW), Euro-Collins (EC), HTK-Bretschneider (HTK),
      reversed St. Thomas' Hospital (ST2) and Krebs-Henseleit (KH). After cold storage,
      the muscles were tested by direct electrical stimulation to obtain the maximum
      twitch tension (Pt) and the maximum tetanus tension (P0). Subsequently, the
      muscles were prepared for morphological analysis. 3. In general, storage at 10
      degrees C caused a gradual decrease of Pt and P0 with time. After 8 h of storage
      in the extracellular-like solutions KH and ST2, the P0 was about 50% (SOL) and
      35% (CT) of control. Eight hours of storage in intracellular-like solutions
      resulted in a P0 of 50% of control for HTK, in a P0 of 40% (SOL) and 67% (CT) for
      UW, but in a P0 of 5% (SOL) and 26% (CT) for EC. These findings corresponded well
      with the morphological observations. 4. It is concluded that the effects of 10
      degrees C storage on skeletal muscle function are not predominantly determined by
      the intra- or extracellular-like composition of the solutions used. Both UW and
      HTK were most effective (P0 > 50% of control) in preserving muscle function.

PMID- 9616262
TI  - Metabolic and myoelectrical effects of acute hypoxaemia during isometric
      contraction of forearm muscles in humans: a combined 31P-magnetic resonance
      spectroscopy-surface electromyogram (MRS-SEMG) study.
AB  - 1. Failure of muscle force during sustained fatiguing contraction is associated
      with myoelectrical and metabolic alterations. However, the inter-relationships
      between these two types of events remain unclear. The purpose of this study was
      to examine the effects of decreased oxygen availability during sustained
      contraction on myoelectrical and metabolic changes, thereby addressing the issue
      of fatigue. 2. 31P-Magnetic resonance spectra and surface electromyograms were
      simultaneously recorded in six subjects (three women and three men) performing
      isometric contraction of forearm flexor muscles sustained at 60% maximum value of
      force under aerobic or acute hypoxaemic conditions (inhalation of a gas mixture
      containing 12% O2). 3. The 5 min hypoxaemic rest preceding contraction did not
      affect the phosphocreatine level and pH value. Under both conditions of oxygen
      availability, the magnitude of metabolic changes remained similar and the
      duration of contraction was unaffected (similar workload). However, hypoxaemia
      significantly reduced the rate of changes in integrated surface electromyogram
      activity measured in the high-frequency band. Correlative analysis of magnetic
      resonance spectroscopy and surface electromyogram data shows that for a given
      surface electromyogram change, metabolic variations were always larger under
      hypoxaemic conditions. 4. These results suggest that hypoxaemia does not alter
      metabolic changes, i.e. decrease in pH and phosphocreatine during static
      contraction. The downward shift of the relationships between myoelectrical and
      metabolic changes under hypoxaemia points to the existence of a better excitation
      contraction coupling in acute hypoxaemia compared with normoxia and this is
      indicative of an adaptative mechanism.

PMID- 9616263
TI  - Mild metabolic alkalosis impairs the natriuretic response to bumetanide in normal
      human subjects.
AB  - 1. This study was designed to test the hypothesis that acid-base status affects
      the response to a loop diuretic in human subjects. The renal responses to
      bumetanide (1 mg intravenously) were studied in eight normal subjects consuming a
      constant diet supplemented for 3 days on three separate occasions with equivalent
      quantities of NaCl, NaHCO3 (metabolic alkalosis) or NH4Cl (metabolic acidosis).
      2. A significant (P < 0.025) reduction in bumetanide-induced diuresis (-40%),
      natriuresis (-21%), and chloruresis (-25%) was observed during NaHCO3 compared
      with NaCl. The renal response was unaltered during NH4Cl. 3. The creatinine and
      para-aminohippurate clearances were unchanged during NaHCO3, as were the blood
      pressure and plasma levels of renin activity, aldosterone and noradrenaline, and
      the plasma volume. 4. Bumetanide excretion was increased during NaHCO3 compared
      with NaCl (2.13 +/- 0.18 versus 1.76 +/- 0.17 micrograms/min, P < 0.025) but was
      not changed during NH4Cl (1.68 +/- 0.26 micrograms/min; not significant). 5.
      Plasma aldosterone concentration was increased 3-fold during acidosis and the
      kaliuretic response to bumetanide was enhanced significantly. 6. In conclusion,
      compared with NaCl, NaHCO3 reduces the diuretic, natriuretic and chloruretic
      response to bumetanide without significant changes in renal haemodynamics, plasma
      volume, the renin-angiotensin-aldosterone axis or the sympathetic nervous system,
      and despite increasing renal bumetanide excretion. NH4Cl enhances aldosterone
      secretion and diuretic-induced kaliuresis.

PMID- 9616264
TI  - Changes in both the membrane and the enzyme content of individual zymogen
      granules are associated with sodium taurocholate-induced pancreatitis in rats.
AB  - 1. After monitoring the changes associated with necrotizing acute pancreatitis in
      rats from early stages to 24 h after infusion of 5% sodium taurocholate in the
      choledocus, we characterized by flow cytometry the zymogen granules that still
      remained in the pancreas 18 h after sodium taurocholate infusion in order to
      explore whether alterations in the enzyme content and/or in the composition of
      the granule membrane could be related to the intracellular mechanisms involved in
      the development of necrotizing acute pancreatitis. 2. Significant increases in
      the haematocrit, plasma and peritoneal exudate amylase levels and oedema were
      observed from the third hour after 5% sodium taurocholate infusion onwards.
      Additionally, cell alterations such as hypergranulation, dilatation of the
      endoplasmic reticulum and autophagic vacuoles were found 3 and 6 h after
      infusion. DNA decrease, degranulation and necrosis were observed from 12 h after
      sodium taurocholate infusion onwards. 3. Flow cytometric measurements of zymogen
      granules isolated from rat pancreas 18 h after 5% sodium taurocholate infusion
      revealed a significant decrease in their internal complexity without major
      changes in their size. Double staining of granules with Tetragonolobus purpureus
      lectin, which specifically binds L-fucose and specific anti-trypsinogen or anti
      amylase antisera, showed that rats with induced pancreatitis have decreased
      amounts of L-fucose in the membrane glycoconjugates and lower enzyme content (70%
      and 30% less for trypsinogen and amylase respectively). 4. A decrease in L-fucose
      in the membrane together with membrane abnormalities observed by electron
      microscopy in zymogen granules isolated 18 h after sodium taurocholate infusion
      indicate an altered synthesis of new granules or lysis of preformed zymogen
      granules which would favour differential loss of granular enzymes, mainly
      trypsinogen, which in turn could increase the severity of disease.

PMID- 9616265
TI  - Dietary fish oil suppresses human colon tumour growth in athymic mice.
AB  - 1. Human colon tumour growth, initiated by subcutaneous inoculation of HT29
      cells, was measured in athymic mice fed ad libitum on high-fat (210 g/kg) diets
      rich in coconut oil (CO), olive oil (OO), safflower oil (SO) or fish oil (FO); a
      low fat (LF; 25 g/kg) diet was used as the control. In one experiment the mice
      were fed the experimental diets for 3 weeks before HT29 cell inoculation and were
      killed 2 weeks post-inoculation. In a second experiment the mice were maintained
      on the LF diet until 4 days post-HT29 cell inoculation; they were then fed the
      experimental diets for 17 days. 2. Compared with mice fed the LF diet, tumour
      size was increased in mice fed the CO, OO or SO diets for 3 weeks before HT29
      cell inoculation; FO feeding did not significantly increase tumour size. 3.
      Feeding mice the CO or OO diets from 4 days post-inoculation increased tumour
      growth rate and tumour size compared with feeding the LF, SO or FO diets; tumour
      growth rate and size did not differ among mice fed the latter diets. 4. The fatty
      acid composition of the tumours was markedly influenced by the fatty acid
      composition of the diet. 5. We conclude that human colon tumour growth is
      influenced by the type of fat consumed in the diet. Human colon tumour growth in
      this model is promoted by feeding high fat diets rich in medium chain saturated
      fatty acids (CO) or monounsaturated fatty acids (OO). A high fat diet, rich in
      long chain n - 3 polyunsaturated fatty acids (FO), does not promote colon tumour
      growth. The effect of a high fat diet rich in n - 6 polyunsaturated fatty acids
      (SO) depends upon the time at which it is fed: if fed before tumour cell
      inoculation such a diet promotes tumour growth, whereas if fed once tumour growth
      is initiated it does not. This suggests that n - 6 polyunsaturated fatty acids
      promote the initiation of colon tumour growth, but do not exert growth-promoting
      effects on colon tumours once they are established.

PMID- 9616266
TI  - Distribution of glutaminase and glutamine synthetase activities in the human
      gastrointestinal tract.
AB  - 1. The activities of the two key enzymes involved in glutamine metabolism,
      glutaminase and glutamine synthetase, were measured in mucosal biopsies taken
      from different sites throughout the human gastrointestinal tract, from oesophagus
      to rectum. 2. The specific activity of glutamine synthetase was highest in the
      stomach (4.5 nmol glutamine formed per minute per mg of protein), but both small
      and large intestine and the oesophagus had little synthesizing capacity (less
      than 0.3 nmol of glutamine formed per minute per mg of protein). 3. Glutaminase
      specific activity was highest in the small intestine (53 nmol glutamate formed
      per minute per mg of protein by duodenal mucosa), intermediate in the large
      intestine and lowest in the oesophagus and stomach (less than 13 nmol of
      glutamate formed per minute per mg of protein). 4. The glutamine concentration in
      the mucosa was lower in the duodenum than in the colon (0.62 and 0.95 mmol/kg wet
      weight respectively), but both were much lower than the measured K(m) values of
      glutaminases obtained from these sites (3.8 and 4.0 nmol/kg wet weight
      respectively). 5. The concentration of glutamine in saliva, stomach juice, bile
      and duodenal juice suggests that very little glutamine passes into the
      gastrointestinal tract via these secretions. 6. The study provides the most
      complete information on the distribution of glutamine synthetase and glutaminase
      along the human gastrointestinal tract, and suggests that (i) both the small and
      large intestines have a high potential for glutamine metabolism, but little
      synthesizing capacity, thus both must derive their glutamine from other sources,
      and (ii) neither the stomach nor the oesophagus have a high glutaminase activity,
      although the stomach has substantial capacity to synthesize glutamine. The
      distribution of the enzymes along the gastrointestinal tract may help rationalize
      the use of glutamine for treating diseases that affect different parts of the
      gastrointestinal tract.

PMID- 9616267
TI  - Whole body protein metabolism in human pulmonary tuberculosis and undernutrition:
      evidence for anabolic block in tuberculosis.
AB  - 1. Differing patterns of protein metabolism are seen in wasting due to
      undernutrition and wasting due to chronic infection. 2. We investigated whole
      body energy and protein metabolism in nine subjects with pulmonary tuberculosis,
      six undernourished subjects (body mass index < 18.5 kg/m2) and seven control
      subjects from an Indian population. Fasting subjects were infused with L-[1
      13C]leucine (2.3 mumol.h-1.kg-1) for 8 h, 4 h fasted then 4 h fed. Leucine
      kinetics were derived from 13C-enrichment of leucine and alpha-ketoisocaproic
      acid in plasma and CO2 in breath. 3. Undernourished subjects, but not
      tuberculosis subjects, had higher rates of whole body protein turnover per unit
      lean body mass than controls [163.1 +/- 9.4 and 148.6 +/- 14.6 mumol compared
      with 142.8 +/- 14.7 mumol leucine/h per kg, based on alpha-ketoisocaproic acid
      enrichment (P = 0.039)]. 4. In response to feeding, protein oxidation increased
      in all groups. Tuberculosis subjects had the highest fed rates of oxidation (47.0
      +/- 10.5 compared with 37.1 +/- 5.4 mumol.h-1.kg-1 in controls), resulting in a
      less positive net protein balance in the fed phase (controls, 39.7 +/- 6.2;
      undernourished subjects, 29.2 +/- 10.6; tuberculosis subjects, 24.5 +/- 9.3; P =
      0.010). Thus fed-phase tuberculosis subjects oxidized a greater proportion of
      leucine flux (33.2%) than either of the other groups (controls, 24.0%;
      undernourished subjects, 24.0%; P = 0.017). 5. Tuberculosis did not increase
      fasting whole body protein turnover but impaired the anabolic response to feeding
      compared with control and undernourished subjects. Such 'anabolic block' may
      contribute to wasting in tuberculosis and may represent the mechanism by which
      some inflammatory states remain refractory to nutrition support.

PMID- 9616268
TI  - Breast cancer following treatment of Hodgkin's disease--more reasons for less
      radiotherapy?

PMID- 9616269
TI  - Is limb amputation necessary for locally advanced soft tissue sarcomas? Pro.

PMID- 9616270
TI  - Is limb amputation necessary for locally advanced soft tissue sarcomas? Contra.

PMID- 9616271
TI  - Is limb amputation necessary for locally advanced soft tissue sarcomas? Arbiter.

PMID- 9616272
TI  - Management of cutaneous melanoma M0: state of the art and trends.
AB  - This article reviews the epidemiology, diagnosis and treatment of cutaneous
      melanoma, including the most recent developments. The combination of positive
      family history, fair complexion, number of nevi, exposure to sun and/or
      chromosomal alterations seem to be implicated in the pathogenesis of cutaneous
      melanoma. Melanomas can be classified according to their growth patterns, and
      tumour microstaging is of straightforward predictive value for survival and risk
      of metastasis, although new factors are also being investigated. As yet, surgical
      excision is the only effective treatment available for primary tumours, resection
      margins varying according to tumour thickness. Elective node dissection is,
      however, no longer advocated for melanomas thinner than 1.5 mm, and there is
      disagreement as to its role for thicker lesions. In contrast, selective node
      dissection at the time of definitive surgery is becoming more widely accepted,
      with regional node dissection being restricted to positive cases. Therapeutic
      dissection is required for lymph node involvement, the most common pattern of
      recurrence from melanoma, which affects nearly 30% of all patients. Complete
      remission rates from isolated limb perfusion, which has been employed in patients
      with multiple recurrences or in-transit metastases, range from 40 to 90%,
      depending on drugs and techniques used in different series; the best responses so
      far have been obtained with tumour necrosis factor in combination with melphalan.
      Patients with thick lesions (> 4 mm) or lymph node metastases have a high risk of
      micrometastases that would warrant adjuvant therapy. The only agent found to
      affect survival is interferon alpha-2.

PMID- 9616273
TI  - Lung cancer in the elderly.

PMID- 9616274
TI  - Breast cancer in patients treated for Hodgkin's disease: clinical and
      pathological analysis of 76 cases in 63 patients.
AB  - In a retrospective multicentric analysis, 63 women treated between 1941 to 1988
      for Hodgkin's disease (HD) subsequently developed 76 breast cancers (BC). The
      median age at diagnosis of HD was 26 years (range 7-67), and 22 women (35%) were
      20 years old or less. Exclusive radiotherapy (RT) was used in 36 women (57%) and
      combined modalities with chemotherapy (CT) in 25 (39%). Breast cancer occurred
      after a median interval of 16 years (range 2-40) and the median age at diagnosis
      of the first BC was 42 years (range 25-73). TNM classification (UICC, 1978)
      showed 10 T0 (non-palpable lesions) (13%), 20 T1 (26%), 22 T2 (29%), 8 T3 (11%),
      7 T4 (9%) and 9 Tx (12%), giving altogether a total of 76 tumours, including,
      respectively, 5 and 8 bilateral synchronous and metachronous lesions. Among the
      68 tumours initially discovered, 53 ductal infiltrating, one lobular infiltrating
      and two medullary carcinomas were found. Moreover, two fibrosarcomas and 10
      ductal carcinoma in situ (DCIS) were also found. Among 50 axillary dissections
      for invasive carcinomas, histological involvement was found in 31 cases (62%). 45
      tumours were treated by mastectomy, without (n = 35) or with (n = 10) RT. 27
      tumours had lumpectomy, without (n = 7) or with RT (n = 20). 2 others received RT
      only, and one only CT. 7 patients (11%) developed isolated local recurrence. 20
      patients (32%) developed metastases and all died; 38 are in complete remission,
      whereas 5 died of intercurrent disease. The 5-year disease-specific survival rate
      by the Kaplan-Meier method was 61%. The 5-year disease-specific survival rate for
      pN0, pN1-3 and pN > or = 3 groups were 91%, 66% and 0%, respectively (P < 0.0001)
      and 100%, 88%, 64% and 23% for the T0, T1, T2 and T3T4 groups, respectively.
      These secondary BCs seem to be of two types: a large number of aggressive tumours
      with a very unfavourable prognosis (especially in the case of pN > 3 and/or
      T3T4); and many tumours with a 'slow development' such as DCIS and microinvasive
      lesions, especially in patients treated exclusively by RT. Moreover, a very
      unusual rate of bilateral tumours (21%) was observed. These secondary BC could be
      'in field', in 'border of field' or 'out of field'. However, a complete analysis
      of doses delivered by supradiaphragmatic irradiation was often very difficult,
      due to large variations in several parameters. We conclude that young women and
      girls treated for HD should be carefully monitored by clinical examination,
      mammography and ultrasonography.

PMID- 9616275
TI  - Retreating recurrent breast cancer with the same CMF-containing regimen used as
      adjuvant therapy. The International Breast Cancer Study Group.
AB  - Breast cancer metastases appearing soon after adjuvant chemotherapy (within 12
      months of its completion) are usually resistant to retreatment with the same
      cytotoxic agents, while relapses occurring later (beyond 12 months) regress when
      rechallenged with the same agents, showing similar response rates observed in non
      pretreated patients with advanced disease. The International Breast Cancer Study
      Group (IBCSG) prospectively explored the efficacy of retreatment for patients
      upon relapse using the same therapy administered during the adjuvant programme.
      87 patients previously treated with an adjuvant CMF (cyclophosphamide,
      methotrexate, 5-fluorouracil) combination chemotherapy (with or without the
      addition of low-dose prednisone and tamoxifen), who had measurable first breast
      cancer relapse, usually after at least 6 months of completion of the adjuvant
      treatment, were treated with CMF. Pretreatment consisted of 1-3 CMF courses in 27
      patients and 4 or more courses in 60 patients. 17 patients were retreated with
      additional tamoxifen or had tamoxifen stopped at relapse. The data of these
      patients are shown separately. 47 of the 86 fully evaluable patients (55%) had an
      objective response, which was complete in 25 (29%). The dominant metastatic type
      and the number of involved sites were the most important factors influencing
      response to retreatment. Patients with soft tissue metastases had a high response
      rate (36/52, 69%) compared with those who had visceral involvement (9/24, 38%) or
      those with bony disease (2/10, 20%) (P = 0.002). In conclusion, response rates to
      retreatment with CMF were similar to those expected in a non-pretreated
      population. The patterns of relapse and the number of metastatic sites were the
      most important factors predicting response to retreatment, while treatment-free
      interval (usually longer than 6 months due to the study design) did not influence
      response rates. This study supports the hypothetic effectiveness of late
      reintroduction of adjuvant cytotoxic therapy (prior to evidence of systemic
      relapse), upon which several current trials are based.

PMID- 9616276
TI  - Response to chemotherapy has predictive value for further survival of patients
      with advanced non-small cell lung cancer: 10 years experience of the European
      Lung Cancer Working Party.
AB  - The aim of this study was the assessment of the predictive value for survival of
      an antitumoral response to three courses of chemotherapy in association with
      various pretreatment characteristics in patients with non-resectable non-small
      cell lung cancer treated by cisplatin- (or carboplatin)-based combination
      regimens. Patients considered for this study were eligible patients with advanced
      non-small cell lung cancer registered in one of the seven trials conducted by the
      European Lung Cancer Working Party from December 1980 to August 1991. All these
      trials tested chemotherapy regimens with platinum derivatives (cisplatin and/or
      carboplatin). In this population of 1052 eligible patients, 752 were assessed in
      this analysis. Data were prospectively collected on 23 pretherapeutic variables
      and objective response after three chemotherapy cycles. The predictive value of
      response to chemotherapy on survival (measured from the time of response
      assessment i.e. 12 weeks after registration in the trial) was studied by
      univariate analysis as well as by multivariate methods (adjustment of the impact
      of several covariates simultaneously on the dependent variable) with adjustment
      for the pretreatment prognostic variables. After three cycles of chemotherapy,
      the global estimated median survival time was 24 weeks with a 95% confidence
      interval of 22-25 weeks. By univariate analysis, we identified an objective
      response to chemotherapy as a highly significant discriminant marker (P < 0.0001)
      for further survival with estimated median survival times of 41 weeks (95% CI: 38
      46) and 19 weeks (95% CI: 17-20), respectively, for the responding and non
      responding patients. In a Cox regression model fitted to the data using a forward
      stepwise procedure, this variable was the first selected explanatory variable.
      Its effect was adjusted by the introduction in the model of initial disease
      extent, Karnofsky performance status, serum calcium level and white blood cell
      count. These results were consistent with those obtained by application of
      recursive partitioning and amalgamation algorithms (RECPAM) which led to a
      classification of the patients into three homogeneous subgroups. Our results,
      using a classical Cox regression model consistent with those highlighted by
      application of a RECPAM analysis, found an objective response to chemotherapy to
      be a predominant predictive factor for further survival, although it did not
      allow any conclusion about a causal relationship. The RECPAM results led to a
      classification of the patients into three subgroups which needs to be validated
      in other series.

PMID- 9616277
TI  - Effect on prognosis of bone marrow infiltration detected by magnetic resonance
      imaging in small cell lung cancer.
AB  - The staging system of limited disease (LD) and extensive disease (ED) is widely
      used and has been shown to provide useful prognostic information in cases of
      small cell lung cancer (SCLC). However, accurate examinations are necessary for
      correct staging. In this report, we evaluated the clinical usefulness of magnetic
      resonance imaging (MRI) of bone marrow in SCLC. 37 patients with LD by standard
      staging and 41 with ED were examined with bone marrow MRI. Results of bone marrow
      MRI did not influence the choice of treatment in patients with LD. For subsequent
      analysis, patients with LD were divided into two groups: patients in whom bone
      marrow infiltration was detected with MRI (MRI-positive LD group) and those in
      whom it was not (MRI-negative LD group). Focal or diffuse metastases to bone
      marrow were detected with MRI in 46% (36/78) of all patients and 35% (13/37) of
      LD patients. The response rates to treatment in patients with MRI-positive LD
      were lower than those in patients with MRI-negative LD (P = 0.006). The survival
      of patients with MRI-positive LD was worse than that of MRI-negative LD
      (generalised Wilcoxon test: P = 0.0157), and closer to that of ED. Multivariate
      analyses using a Cox model that included the result of bone marrow MRI,
      performance status, chemotherapy regimen, radiotherapy and serum lactose
      dehydrogenase (LDH) level showed that the result of bone marrow MRI remained a
      prognostic factor in SCLC patients with limited disease. Bone marrow examination
      with MRI is useful for better staging of SCLC. According to our analysis of
      response rates and survival, MRI-positive LD should be considered a type of ED.

PMID- 9616278
TI  - nm23 Protein expression in larynx cancer and the relationship with metastasis.
AB  - The nm23 gene, which encodes nucleoside diphosphate (NDP) kinase, is proposed as
      a metastatic suppressor gene and has been demonstrated to correlate inversely
      with metastatic potential in several tumours. To elucidate the role of nm23 in
      larynx carcinomas, we examined using immunohistochemistry the expression of the
      nm23 protein in matched sets of primary tumours and metastatic lymph nodes. nm23
      Protein was expressed in all the carcinomas as well as in non-neoplastic larynx
      mucosa. Overexpression of nm23 protein was found in the majority of primary
      tumours compared with corresponding normal mucosa, while decreased expression was
      associated with poor differentiation and distant metastasis and/or recurrence. No
      significant difference in age, sex and stage was found between primary tumours
      with high and low nm23 protein expression. These results suggest that decreased
      nm23 protein expression may play a role in metastasis and/or recurrence in larynx
      cancer and therefore could be used as a prognostic factor.

PMID- 9616279
TI  - Prognostic significance of microsatellite instability in patients with gastric
      carcinoma.
AB  - A proportion of gastric adenocarcinomas exhibit replication errors manifested as
      microsatellite instability. The clinicopathological and prognostic significance
      of this abnormality remains uncertain. This study aimed to determine the
      importance of microsatellite instability by analysing a large series of gastric
      carcinomas from an English population. Using a novel fluorescent polymerase chain
      reaction technique, we amplified 11 microsatellite sequences from paired normal
      and carcinoma DNA from 101 patients who underwent a potentially curative
      resection for gastric carcinoma. Overall, 21% of cases demonstrated
      microsatellite instability in at least one locus. At least four loci were
      examined in each case. A replication error positive phenotype (minimum of 29% of
      loci affected) was detected in 9% of cases. There was no statistically
      significant association between the presence of microsatellite instability or
      replication error positive phenotype and the patient's age, sex, tumour site,
      stage, node status, histological subtype or grade. Carcinomas confined to the
      mucosa or submucosa (T1) showed a significantly higher frequency of instability
      and replication error positive phenotypes than T3 lesions (P = 0.03 and P = 0.05,
      respectively). A larger proportion of patients who were microsatellite
      instability or replication error positive were alive at 5 years compared with
      those who were negative but this did not reach statistical significance (P = 0.15
      and P = 0.16, respectively). We identified a subset of gastric carcinomas from a
      relatively low-risk population which showed evidence of microsatellite
      instability. There were no statistically significant 5-year survival advantages
      in cases demonstrating microsatellite instability or replication error positive
      phenotypes. The detection of microsatellite instability is of limited prognostic
      value in gastric carcinoma.

PMID- 9616280
TI  - The effect of 2-h infusion of 2-chlorodeoxyadenosine (cladribine) with prednisone
      in previously untreated B-cell chronic lymphocytic leukaemia.
AB  - 2-Chlorodeoxyadenosine (2-CdA) is a new antimetabolite chemotherapeutic agent
      active in indolent lymphoid malignancies. In this retrospective study, 69
      previously untreated patients with B-cell chronic lymphocytic leukaemia (B-CLL)
      were treated with 2-CdA administered at a dose of 0.12 mg/kg daily in 2-h
      intravenous infusion for 5 consecutive days. 45 patients also received prednisone
      30 mg/m2 orally each day for 5 days starting with 2-CdA courses. Patients were
      given 2-6 courses (mean 4.6) of 2-CdA repeated usually at monthly intervals. If a
      complete response was achieved, no further 2-CdA courses were administered.
      Guidelines for response were those developed by the NCI Sponsored Working Group.
      Complete response (CR) was achieved in 26 (38%) and partial response (PR) in 27
      (39%) cases, giving an overall response rate of 77%. 16 patients (23%) did not
      respond to 2-CdA. In the subgroup of 45 patients receiving 2-CdA with prednisone,
      CR was obtained in 15 (33%) and PR in 20 (44%) patients giving an overall
      response rate of 78%. CR was achieved in 11 (46%) out of 24 patients treated only
      with 2-CdA and in 7 cases (29%) PR was observed, giving an objective response
      rate of 75%. The differences between both subgroups were not statistically
      significant. However, we observed a relationship between the response and the
      number of courses of 2-CdA given in patients receiving and those not receiving
      prednisone. In the subgroup receiving 2-CdA with prednisone, an earlier response
      to 2-CdA was observed. In this group a response was achieved in 9 (20%) patients
      after two courses of 2-CdA and in 18 (40%) after four courses. In the subgroup
      receiving only 2-CdA, 17 (71%) responses were obtained after six cycles.

PMID- 9616282
TI  - Ewing's sarcoma of the pelvis: changes over 25 years in treatment and results.
AB  - The pelvic localisations of Ewing's sarcoma have the worst prognosis due to large
      size at diagnosis, frequent distant metastases, radiosensitive organs next to the
      tumour and difficult surgery. The purpose of the present study was to analyse
      treatment results over a period of 25 years and to investigate the impact of
      newer chemotherapy schedules, improved radiotherapy techniques and newer surgical
      methods on the prognosis. 35 children and young adults were identified from 1967
      to 1994 for whom diagnosis, presentation, performed treatment and outcome were
      available. Tumour size, as measured from CT scans, response to chemotherapy and
      radiotherapy target volume, could be reviewed in the later years. Actuarial 5
      year survival for the whole group was 31% and for the 24 non-metastatic patients
      40%, with a disease-free interval of 19%. Tumour size could be measured in 27
      patients and ranged from 36 to 1540 cm3. There were 12 local recurrences, 1 in
      the 4 patients treated with surgery. After 1983, 9 out of 17 irradiated patients
      developed local failure. 3 patients had adequate fields and one a close field
      which did not cover completely the prechemotherapy extent and 3 of these
      recurred. All 4 patients with stable disease after neoadjuvant CT failed locally,
      not withstanding high-dose radiotherapy. The mean length of neoadjuvant CT tended
      to be shorter in patients without local relapse. There was no significant
      difference in survival before and after 1983.

PMID- 9616281
TI  - Loss of physical functioning among geriatric cancer patients: relationships to
      cancer site, treatment, comorbidity and age.
AB  - This study investigated differences in physical functioning and physical role
      limitations according to cancer site and treatment modality in a sample of 590
      patients 65 years and older diagnosed with breast, colon, lung or prostate
      cancer. Analysis of covariance procedures were utilised to test for differences
      in levels of physical functioning and physical role limitations according to
      cancer site and treatment modality, adjusting for differences in age, comorbid
      conditions and retrospective physical functioning. Physical functioning and
      physical role limitations were measured using two subscales of the Medical
      Outcomes Studies MOS 36-item Short Form Health Survey (SF-36). Physical
      functioning prior to diagnosis, and to a lesser degree comorbidity, contributed
      significantly to current levels of physical functioning and physical role
      limitations. Patients with lung cancer reported lower physical functioning and
      physical role limitation scores than patients with prostate cancer, and patients
      treated with surgery only reported lower physical functioning and physical role
      limitation scores than patients treated with neither surgery nor radiation. No
      gender differences were observed among the reduced sample consisting of patients
      with colon or lung cancer. It is important not only that physicians and
      oncologists are cognizant of the fact that some cancers (particularly lung
      cancer) may be more physically debilitating than others, but that the patient's
      history of comorbid conditions and pre-existing physical limitations may be
      important factors in predicting current physical functioning.

PMID- 9616283
TI  - High-dose chemotherapy with carboplatin, etoposide and cyclophosphamide followed
      by a haematopoietic stem cell rescue in patients with high-risk retinoblastoma: a
      SFOP and SFGM study.
AB  - This study investigates the role of high-dose chemotherapy with haematopoietic
      stem cell rescue as consolidation treatment in high-risk retinoblastoma
      (extraocular disease at diagnosis or relapse or invasion of cut end of optic
      nerve). 25 patients received high-dose chemotherapy including carboplatin (250
      mg/m2/day from day 1 to day 5 for the 6 first patients and 350 mg/m2/day from day
      1 to day 5 for the other patients), etoposide (350 mg/m2/day from day 1 to day 5)
      and cyclophosphamide (1.6 g/m2/day from day 2 to day 5) (CARBOPEC) followed by
      autologous haematopoietic stem cell rescue. 19 patients received this drug
      combination for chemosensitive extraocular relapse. The other 6 patients with
      histological high-risk factors were given this treatment as consolidation after
      enucleation and conventional chemotherapy. The three year disease-free survival
      was 67.1%. In 7 of the 9 relapsing patients, the first site of relapse was the
      central nervous system. All patients with central nervous system disease died
      except one. The main toxicity was haematological and digestive (mucositis and
      diarrhoea). 2 of the 13 evaluable patients had grade III and IV ototoxicity. One
      patient experienced an acute grade I reversible cardiotoxicity. The CARBOPEC
      regimen seems to be a promising therapeutic strategy in patients with high-risk
      retinoblastoma, especially those with bone and/or bone marrow involvement. This
      treatment did not improve the outcome of patients with central nervous system
      disease.

PMID- 9616284
TI  - Cancer in the offspring of parents with lung cancer.
AB  - Despite several studies on the role of passive smoking in the development of
      childhood cancer, particularly leukaemia, lymphomas and brain cancer, no
      definitive answer has yet been provided. The aim of the cohort study reported
      here was to analyse the incidence of cancer in the offspring of young lung cancer
      patients on the basis of the assumption that all of the offspring were exposed
      passively to smoke. The files of the Danish Cancer Registry provided 3348 cases
      of lung cancer patients born after 1935, and their offspring (n = 6417) were
      identified through the Danish Population Register. The files of the offspring
      were then linked with the files of the Danish Cancer Registry and the numbers of
      cancers observed in the offspring were compared with those expected from national
      age-specific and calendar-time-specific rates. A total of 135,333 person-years
      was the basis for analysis. Twenty-six cancers were observed, with 30.3 expected,
      yielding a standardised incidence ratio (SIR) of 0.9 (90% confidence interval
      (CI), 0.6-1.2). There was no excess of brain tumours, leukaemias or lymphomas.
      Stratification for sex of the lung cancer patients revealed a non-significantly
      increased risk for both non-Hodgkin's lymphoma (three cases; SIR = 3.4; 90% CI:
      0.9-8.7) and Hodgkin's disease (three cases; SIR = 2.6; 90% CI: 0.7-6.6) in the
      offspring of female lung cancer patients. These results suggest that there is
      little evidence of an excess cancer risk in childhood, whether due to passive
      smoking or to as yet unidentified genetic factors, among the offspring of people
      who develop lung cancer. However, the results are limited by the fact that
      exposure was only assessed indirectly, with no measurement of actual cigarette
      consumption made.

PMID- 9616285
TI  - Hodgkin's disease in a national and hospital population: trends over 20 years.
AB  - The aim of the study was to investigate the incidence rate and time trends in a
      national registry population of Hodgkin's disease (HD) and the effects of
      selection in a hospital population. A national registry population of all HD
      patients from Norway and a hospital population of HD patients treated at the
      Norwegian Radium Hospital (NRH) were studied retrospectively from 1971 to 1993.
      The incidence of non-Hodgkin's lymphomas (NHL) in Norway increased steadily from
      1961 in contrast to a stable incidence pattern for HD before 1980 and a
      decreasing incidence since 1980. Due to improved diagnostic tools after 1980, an
      increasing proportion of patients previously diagnosed as lymphocyte depleted and
      unclassified HD were classified as NHL. As these histologies are dominant in
      older patients, the incidence of older patients with HD and the total population
      of HD have decreased since 1980. As a result, the proportion of young adults with
      a favourable histology has increased. These changes may partly explain the
      increased patient survival observed both in the national and the hospital
      population. The hospital population comprised 92% of patients aged 15-39 years,
      80% of patients aged 40-59 years and 53% of patients aged > 60 years in the
      national population. The selection of younger patients in the hospital material
      may explain a higher survival rate as compared with the national population.

PMID- 9616286
TI  - Differential effects of dietary phyto-oestrogens daidzein and equol on human
      breast cancer MCF-7 cells.
AB  - The in vitro effects of two closely related phyto-oestrogens daidzein and equol
      on the oestrogen receptor positive human breast cancer cells MCF-7 were examined.
      There is differential metabolism of daidzein in humans, and the conversion of
      daidzein to equol by intestinal microbes occurs only in 30% of the population.
      The differential potency of these two compounds is thus of considerable
      importance since it may be likely that the relative risk of hormone-dependent
      cancers may be higher in 'non-responders'. In the present study, we compared the
      ability of both these compounds to induce mRNA expression of the oestrogen
      responsive pS2 gene, to compete with oestradiol for binding to the oestrogen
      receptor (ER) and to affect cellular proliferation. Our studies demonstrate that
      equol is a 100-fold more potent than daidzein in stimulating an oestrogenic
      response. Equol was also more effective than daidzein in competing with 3H
      oestradiol for binding to the ER. These results suggest that equol has a higher
      affinity for the ER. Both compounds stimulated the growth of MCF-7 cells in a
      concentration-dependent manner (10(-8)-10(-5)M). Although equol exhibits
      oestrogenic activity, exposure of MCF-7 cells to equol simultaneously with
      oestradiol was effective in reducing pS2 mRNA expression. This was not observed
      with daidzein. However, long-term exposure of MCF-7 cells to both daidzein and
      equol resulted in the downregulation of ER mRNA expression.

PMID- 9616287
TI  - A BRCA1 founder mutation, identified with haplotype analysis, allowing
      genotype/phenotype determination and predictive testing.
AB  - We searched for a founder mutation in a population from one geographic region of
      Norway with prevalent breast/ovarian cancer families. We sampled 33
      breast/ovarian cancer families and determined haplotypes of four markers linked
      to the BRCA1 region. Of the affected 33 index women, 13 (39.4%) shared one
      haplotype. In five (15% of total), an identical mutation was indicated by an
      abnormal truncated protein test (PTT) of exon 11 and shown to represent a
      1675delA mutation. In the other index women, PTT of exon 11 showed no
      abnormality. No other BRCA1 founder mutation of this prevalence is likely because
      no other haplotype was more frequent in affecteds than in controls. All families
      with the 1675delA mutation in this geographic region may be considered as part of
      one large kindred. This allows a genotype-phenotype correlation to be precisely
      determined and used in genetic counselling for predictive testing within this
      kindred. Identification of identical haplotypes between unrelated affected
      individuals may be used to estimate the extent of founder effects for any mapped
      disease, without knowledge of the specific founder mutation.

PMID- 9616288
TI  - Frequent allelic losses on chromosome 13q in human male breast carcinomas.
AB  - Loss of genetic material on chromosomes 13q and 17 has been suggested to be of
      importance in the initiation and progression of female breast cancer, but their
      involvement is less well illustrated in male breast carcinomas. The present study
      was designed to investigate the incidence of allelic loss and microsatellite
      instability for chromosomes 13q, 17p and 17q in 13 sporadic male breast
      carcinomas using matched normal-tumour DNA samples and seven polymorphic
      microsatellite markers. Genetic imbalance was found in one or more informative
      markers in 85% of the patients, with more frequent loss of heterozygosity and
      microsatellite instability at loci on chromosome 13q. Thus, a high incidence of
      allelic losses was observed at the retinoblastoma gene (4/6) and likewise at the
      D13S263 locus (7/12), which also exhibited the highest frequency of
      microsatellite instability. The intragenic microsatellite in intron 1 of the TP53
      gene on chromosome 17p revealed loss of heterozygosity in 3 of 8 informative
      patients. The investigated proximal region of chromosome 13q is postulated to
      harbour several potential tumour suppressor genes associated with female breast
      cancer. The high incidence of allelic losses at the D13S263 microsatellite,
      located distal to both the BRCA2 and the Brush-1 loci but proximal to the
      retinoblastoma gene, possibly indicates the presence of an additional tumour
      suppressor gene which may be involved in male breast carcinomas. However, this
      hypothesis needs verification in an extended study of male breast carcinomas.

PMID- 9616289
TI  - Transforming growth factor-beta isoform expression in human ovarian tumours.
AB  - The expression patterns of members of the transforming growth factor-beta (TGF
      beta) family were analysed in 96 primary ovarian tumours by RNAse protection
      assay. mRNA for the three mammalian isoforms, TGF-beta 1, TGF-beta 2 and TGF-beta
      3, was detected in 46, 66 and 66% of 74 malignant tumours, respectively, with the
      predominant patterns of expression being either dual or triple co-expression. TGF
      beta II receptor expression, detected by reverse-transcription PCR, was present
      in 92% malignant tumours. Expression patterns were similar between malignant,
      borderline and benign tumours, although TGF-beta 1 incidence was reduced in
      benign tumours. In malignant tumours, the incidence of TGF-beta 1 expression was
      less than that of either TGF-beta 2 (P = 0.02) or TGF-beta 3 (P = 0.0014), while
      in both malignant and borderline tumours, TGF-beta 2 and TGF-beta 3 tended to be
      co-expressed. Aneuploid tumours were more likely than diploid tumours to express
      multiple rather than single forms of TGF-beta (P = 0.018). The incidence of TGF
      beta 1 expression was reduced in PR-moderate/rich (PR > 20 fmol/mg protein)
      relative to PR-negative/poor tumours (P = 0.048), while TGF-beta 3 expression was
      increased in ER-moderate/rich (ER > 20 fmol/mg protein) tumours compared to ER
      negative/poor tumours (P = 0.0012). Expression of TGF-beta 3, but not TGF-beta 1
      or TGF-beta 2, was associated with advanced stage disease (P = 0.014) and, in the
      malignant group, reduced survival (P = 0.02) with a hazard ratio of 2.6. These
      data suggest a possible role for TGF-beta 3 in the progression of ovarian cancer.

PMID- 9616290
TI  - Preclinical activity of trans-indazolium[tetrachlorobisindazoleruthenate(III)]
      (NSC 666158; IndCR; KP 1019) against tumour colony-forming units and
      haematopoietic progenitor cells.
AB  - Trans-indazolium[tetrachlorobisindazoleruthenate(III)] (KP 1019) is a new heavy
      metal complex with promising activity against tumour cell lines and in animal
      models. We studied the antineoplastic effects of KP 1019 (final concentrations:
      1, 10, 100 micrograms/ml) on in vitro proliferation of clonogenic cells from
      freshly explanted human tumours in a capillary soft agar cloning system, and
      compared the activity of KP 1019 with conventional antineoplastic agents. 53 of
      75 specimens (71%) showed adequate growth in controls. KP 1019 inhibited tumour
      colony formation in a concentration-dependent manner in both short- (1 h) and
      long-term (21 d) exposure experiments. KP 1019 at 100 micrograms/ml with 1 h
      exposure was as active as bleomycin, cisplatin, doxorubicin, etoposide, 5
      fluorouracil, methotrexate, mitomycin-C and vinblastine, with only paclitaxel
      more active than KP 1019 (P = 0.002). The antitumour activity of KP 1019 was more
      pronounced after long-term exposure, indicating the potential schedule dependency
      of KP 1019. Activity was observed against non-small cell lung, breast and renal
      cancer. We conclude that if appropriate plasma levels can be achieved in
      patients, KP 1019 may have significant clinical activity against a variety of
      different tumour types.

PMID- 9616291
TI  - Expression of the aromatic L-amino acid decarboxylase mRNA in human tumour cell
      lines of neuroendocrine and neuroectodermal origin.
AB  - Neuroendocrine differentiation of lung tumours is characterised by the expression
      of several neuroendocrine markers and is confined mostly to specific histological
      subtypes, i.e. small cell carcinomas and carcinoids. One of the markers seen in
      neuroendocrine tumours, high activity of the aromatic L-amino acid decarboxylase
      (AADC), is helpful in distinguishing the classic and variant small cell lung
      tumour subtypes. Here, we have analysed the expression and quantified the level
      of mRNA coding for AADC in human tumour cell lines by use of the reverse
      transcription and polymerase chain reaction (RT-PCR). High amounts of mRNA were
      detected in classic small cell lung carcinomas and a neuroblastoma cell line.
      Other cell lines (melanomas, non-small cell lung carcinomas and osteosarcoma)
      also showed AADC expression, but the levels were 2-3 orders lower. Also, the
      tissue-specific (neuronal versus liver-specific) mRNA type has been estimated.
      Small cell lung carcinomas, neuroblastoma and melanoma expressed messenger RNA
      specific for neuronal tissues. Importantly, the non-small cell lung carcinoma
      cell lines expressed either liver-specific (non-neuronal) mRNA (cell line A549)
      or predominantly the neuronal (cell line NCI-H520) AADC message. These data
      indicate that a range of tumour cell lines transcribe the AADC gene and that two
      distinct types of AADC mRNA which reflect the embryonal (neuronal or non
      neuronal) origin of the tumour may be produced in non-small cell lung cancer
      cells.

PMID- 9616292
TI  - A pharmacokinetic and pharmacodynamic study in vivo of human HT29 tumours using
      19F and 31P magnetic resonance spectroscopy.
AB  - 19F-MRS (magnetic resonance spectroscopy) was used to study the pharmacokinetics
      of 5-fluorouracil (5-FU) in human (HT29) tumour xenografts, with and without
      pretreatment of the mice using either thymidine (40 min) or interferon-alpha (2
      and 24 h). A 200 mg/kg i.p. bolus dose of 5-FU was eliminated from control
      tumours with a t1/2 of 25.4 +/- 2 min (mean +/- SEM, n = 11), while both
      thymidine (500 mg/kg) and interferon (50,000 IU/mouse) significantly increased
      t1/2 to 36.5 +/- 6.1 (n = 5) and 48.1 +/- 13.6 min (n = 4), respectively (P =
      0.04, Gabriel's ANOVA). Thymidine increased 5-FU anabolism to cytotoxic 5
      fluoronucleotides, and decreased the amount of tumour catabolites; the latter
      probably recirculated from liver since isolated HT29 cells did not catabolize 5
      FU. These in vivo observations were confirmed by 19F-MRS quantification of tumour
      extracts. Interferon did not significantly affect 5-FU metabolism in the tumour
      or liver, nor the 5-FU t1/2 in liver. Treatment of tumours with 5-FU or
      interferon had no effect on tumour growth, whereas the combination strongly
      inhibited growth. 31P-MRS of HT29 tumours showed that 2 and 24 h after i.p.
      injections of interferon there was a significant increase in the pHint of 0.3 +/-
      0.04 units (P = 0.002), while pHext and the tumour NTP/Pi ratio were unchanged.
      The large increase in the negative pH gradient (-delta pH) across the tumour
      plasma membrane caused by interferon suggest the delta pH may be a factor in
      tumour retention of 5-FU, as recently shown in isolated tumour cells.

PMID- 9616293
TI  - Management of chemotherapy-related anaemia with low-dose recombinant human
      erythropoietin in patients with small cell lung cancer.
AB  - We examined the efficacy of low-dose erythropoietin in the management of
      chemotherapy-related anaemia in patients with small cell lung cancer (SCLC). We
      gave recombinant human erythropoietin A (rHuEPO) to 63 SCLC patients, 30 with
      limited disease (LD) and 33 with extensive disease (ED) who underwent
      chemotherapy with carboplatin, etoposide and ifosfamide and had previously
      received blood transfusions for chemotherapy-related anaemia. rHuEPO was given at
      a dose of 2000 IU subcutaneously three times per week for 2 weeks after every
      chemotherapy cycle, starting 48 h after the end of chemotherapy. Before the use
      of rHuEPO, all patients in both groups had to be transfused after a mean of 5.5
      CT cycles. In 64 CT cycles following administration of rHuEPO, only 5/30 LD
      patients (17%) had to be transfused in six cycles (9%). In 88 cycles following
      the use of rHuEPO, 7/33 ED patients (21%) had to be transfused in 11 cycles
      (12.5%). Haemoglobin values in patients with ED (but not those with LD) were
      significantly improved after rHuEPO administration on both day 14 and day 28
      after chemotherapy. No adverse effects were recorded. rHuEPO considerably
      decreased the degree of anaemia and the need for blood transfusion at doses
      markedly lower (25-30 IU/kg body weight) than those reported in the literature so
      far (150 IU/kg body weight), without toxicity.

PMID- 9616294
TI  - 'Dosimetric breast size': a new and useful parameter for the prediction of local
      recurrence after breast conservative treatment.
AB  - To evaluate the risk of local recurrence following breast-conserving therapy for
      breast cancer, we measured the distance between each entry point of the
      irradiation on the surface of the breast in line with the axis of the external
      and internal tangential fields (dosimetric breast size). 652 breast cancer
      patients were retrospectively analysed, with a median age of 51 years and a
      median follow-up of 99 months (range 84-192). There were 50 local recurrences, 44
      isolated and 6 associated with nodal recurrence or metastases. The global rates
      of local recurrences at 5 and 10 years were 5.3% and 9%, respectively (Kaplan
      Meier analysis). Following a Cox's multivariate analysis, the only significant
      and independent parameters related to local recurrence were quality of excision,
      age at diagnosis and dosimetric breast size. For a small dosimetric breast size
      (< or = 10 cm), the rate of local recurrence was 14.1 compared with 11.8 for
      medium dosimetric breast size (> 10 cm-< or = 12 cm) and 5.2 for large dosimetric
      breast size (> 12 cm). If the analysis was restricted to only those with complete
      excision, then the relative risk for a patient with a small dosimetric breast
      size was three times that for a large breast size.

PMID- 9616295
TI  - Effective intrahepatic administration of gemcitabine after failure of doxorubicin
      in metastatic breast cancer.

PMID- 9616296
TI  - Post-transplant EBV-associated pancreas carcinoma.

PMID- 9616297
TI  - Impact of histamine and histamine2 receptor antagonists on quality of life and
      antitumour responses: results of a pilot trial.

PMID- 9616298
TI  - Recurrent ifosfamide-induced hyponatraemia.

PMID- 9616299
TI  - From genes to genome biology: a new era in Helicobacter pylori research.

PMID- 9616300
TI  - The failing malignant liver.

PMID- 9616301
TI  - Gut epithelium: food processor for the mucosal immune system?

PMID- 9616302
TI  - Is the hepatocyte a Trojan horse for hepatitis C virus?

PMID- 9616303
TI  - Pathogenesis of inflammatory bowel disease: transcription factors in the
      spotlight.

PMID- 9616304
TI  - Viral vectors expressing immunoregulatory cytokines to treat inflammatory bowel
      disease.
AB  - Inflammatory bowel disease (IBD) is characterised by altered immunoregulation and
      augmented synthesis of nitric oxide. The purpose of this study was to determine
      the effects of exogenous IL-4, introduced by a recombinant human type 5
      adenovirus (Ad5) vector, on the tissue injury associated with an experimental
      model of colonic immune activation and inflammation. Colitis was induced in rats
      by the intrarectal administration of trinitrobenzene sulfonic acid (TNB)
      dissolved in 50% ethanol, and control rats received saline via the same route. 1
      h later, all rats were randomized into two groups. The first group was injected
      intraperitoneally (i.p.) with 3.0 x 10(6) plaque forming units (PFUs) of Ad5
      transfected with murine interleukin-4 (Ad5IL-4) and the second group was injected
      i.p. with the same amount of Ad5 expressing the Escherichia coli Lac Z gene
      (Ad5LacZ). One-half of the colitic and controls rats were injected again with 3.0
      x 10(6) PFUs of Ad5IL-4 or Ad5LacZ on day 3 of the 6-d study. When introduced
      once or twice via the peritoneal route into control rats Ad5LacZ was localised to
      the serosal lining of the peritoneal cavity, the diaphragm and the liver on day
      6. One or two injections of Ad5IL-4 into rats also produced measurable levels of
      circulating IL-4. TNB-colitis in both Ad5LacZ-treated groups was associated with
      pronounced elevations in serum IFN-gamma, and mucosal ulceration of the distal
      colon. Myeloperoxidase and inducible nitric oxide synthase II (NOS II) synthetic
      activity were also increased by 30- and fivefold, respectively, above control
      levels in the distal colon. However, two injections of AD5IL-4 into colitic rats
      caused the overexpression of IL-4, and significantly inhibited tissue damage,
      serum and colon IFN-gamma levels and myeloperoxidase activity in the distal
      colon. In addition, NOS II gene expression and NOS II nitric oxide synthesis was
      significantly inhibited. No therapeutic effect was observed in rats injected once
      with AD5IL-4. Thus, IL-4, introduced by Ad5, is therapeutic during acute
      inflammation in the rat colon. The therapeutic effect of IL-4 was associated with
      an inhibition of inducible nitric oxide expression and a reduction in nitric
      oxide synthesis.

PMID- 9616305
TI  - A randomised controlled comparison of injection, thermal, and mechanical
      endoscopic methods of haemostasis on mesenteric vessels.
AB  - BACKGROUND AND AIMS: A randomised controlled comparison of haemostatic efficacy
      of mechanical, injection, and thermal methods of haemostasis was undertaken using
      canine mesenteric vessels to test the hypothesis that mechanical methods of
      haemostasis are more effective in controlling haemorrhage than injection or
      thermal methods. The diameter of arteries in human bleeding ulcers measures up to
      3.45 mm; mesenteric vessels up to 5 mm were therefore studied. METHODS:
      Mesenteric vessels were randomised to treatment with injection sclerotherapy
      (adrenaline and ethanolamine), bipolar diathermy, or mechanical methods (band,
      clips, sewing machine, endoloops). The vessels were severed and haemostasis
      recorded. RESULTS: Injection sclerotherapy and clips failed to stop bleeding from
      vessels of 1 mm (n = 20) and 2 mm (n = 20). Bipolar diathermy was effective on
      8/10 vessels of 2 mm but failed on 3 mm vessels (n = 5). Unstretched elastic
      bands succeeded on 13/15 vessels of 2 mm but on only 3/10 vessels of 3 mm. The
      sewing machine achieved haemostasis on 8/10 vessels of 4 mm but failed on 5 mm
      vessels (n = 5); endoloops were effective on all 5 mm vessels (n = 5).
      CONCLUSIONS: Only mechanical methods were effective on vessels greater than 2 mm
      in diameter. Some mechanical methods (banding and clips) were less effective than
      expected and need modification. Thermal and (effective) mechanical methods were
      significantly (p < 0.01) more effective than injection sclerotherapy. The most
      effective mechanical methods were significantly more effective (p < 0.01) than
      thermal or injection on vessels greater than 2 mm.

PMID- 9616306
TI  - Increased secretion of pro-inflammatory cytokines by circulating
      polymorphonuclear neutrophils and regulation by interleukin 10 during intestinal
      inflammation.
AB  - BACKGROUND: Concentrations of pro-inflammatory cytokines are increased in the
      intestinal mucosa of patients with active inflammatory bowel disease (IBD).
      Polymorphonuclear neutrophil granulocytes (PMN) are the most abundant cell type
      in intestinal lesions in IBD. Interleukin 10 (IL-10) is an important contra
      inflammatory cytokine which induces downregulation of pro-inflammatory cytokines.
      AIMS: To investigate whether PMN from patients with IBD or infectious colitis,
      respectively, secrete increased amounts of pro-inflammatory cytokines and can be
      regulated by IL-10. METHODS: Secretion (ELISA) as well as corresponding mRNA
      levels (semiquantitative RT-PCR) of pro-inflammatory cytokines (IL-1 beta, TNF
      alpha) and of IL-1 receptor antagonist were assessed in peripheral PMN. RESULTS:
      PMN from patients with IBD are primed to secrete enhanced amounts of pro
      inflammatory cytokines accompanied by detection of corresponding mRNAs in
      comparison with normal controls. This finding is not specific for IBD but rather
      reflects intestinal inflammation in general. IL-10 markedly inhibited
      proinflammatory cytokine secretion as well as corresponding mRNA concentrations.
      CONCLUSIONS: PMN are an important source of pro-inflammatory cytokines in
      patients with intestinal inflammation and can be downregulated by IL-10.

PMID- 9616307
TI  - Activation of nuclear factor kappa B inflammatory bowel disease.
AB  - BACKGROUND: Expression of pro-inflammatory cytokines is increased in the
      intestinal lamina propria of patients with inflammatory bowel disease (IBD).
      Nuclear factor kappa B (NF kappa B) controls transcription of inflammation genes.
      On activation, NF kappa B is rapidly released from its cytoplasmic inhibitor (I
      kappa B), transmigrates into the nucleus, and binds to DNA response elements in
      gene promoter regions. AIMS: To investigate whether increased activation of NF
      kappa B is important in IBD and may be down-regulated by anti-inflammatory
      treatment. METHODS: Activation of NF kappa B was determined by western blot
      assessment and electrophoretic mobility shift assay in nuclear extracts of
      colonic biopsy samples as well as lamina propria mononuclear cells. RESULTS:
      Nuclear levels of NF kappa B p65 are increased in lamina propria biopsy specimens
      from patients with Crohn's disease in comparison with patients with ulcerative
      colitis and controls. Increased activation of NF kappa B was detected in lamina
      propria mononuclear cells from patients with active IBD. Corticosteroids strongly
      inhibit intestinal NF kappa B activation in IBD in vivo and in vitro by
      stabilising the cytosolic inhibitor I kappa B alpha against activation induced
      degradation. CONCLUSIONS: In both IBDs, but particularly Crohn's disease,
      increased activation of NF kappa B may be involved in the regulation of the
      inflammatory response. Inhibition of NF kappa B activation may represent a
      mechanism by which steroids exert an anti-inflammatory effect in IBD.

PMID- 9616308
TI  - Impairment of intestinal glutathione synthesis in patients with inflammatory
      bowel disease.
AB  - BACKGROUND: Reactive oxygen species contribute to tissue injury in inflammatory
      bowel disease (IBD). The tripeptide glutathione (GSH) is the most important
      intracellular antioxidant. AIMS: To investigate constituent amino acid plasma
      levels and the GSH redox status in different compartments in IBD with emphasis on
      intestinal GSH synthesis in Crohn's disease. METHODS: Precursor amino acid levels
      were analysed in plasma and intestinal mucosa. Reduced (rGSH) and oxidised
      glutathione (GSSG) were determined enzymatically in peripheral blood mononuclear
      cells (PBMC), red blood cells (RBC), muscle, and in non-inflamed and inflamed
      ileum mucosa. Mucosal enzyme activity of gamma-glutamylcysteine synthetase (gamma
      GCS) and gamma-glutamyl transferase (gamma GT) was analysed. Blood of healthy
      subjects and normal mucosa from a bowel segment resected for tumor growth were
      used as controls. RESULTS: Abnormally low plasma cysteine and cystine levels were
      associated with inflammation in IBD (p < 10(-4)). Decreased rGSH levels were
      demonstrated in non-inflamed mucosa (p < 0.01) and inflamed mucosa (p = 10(-6))
      in patients with IBD, while GSSG increased with inflammation (p = 0.007) compared
      with controls. Enzyme activity of gamma GCS was reduced in non-inflamed mucosa (p
      < 0.01) and, along with gamma GT, in inflamed mucosa (p < 10(-4)). The GSH
      content was unchanged in PBMC, RBC, and muscle. CONCLUSIONS: Decreased activity
      of key enzymes involved in GSH synthesis accompanied by a decreased availability
      of cyst(e)ine for GSH synthesis contribute to mucosal GSH deficiency in IBD. As
      the impaired mucosal antioxidative capacity may further promote oxidative damage,
      GSH deficiency might be a target for therapeutic intervention in IBD.

PMID- 9616309
TI  - Low dose oral pH modified release budesonide for maintenance of steroid induced
      remission in Crohn's disease. The Budesonide Study Group.
AB  - BACKGROUND: The relapse rate after steroid induced remission in Crohn's disease
      is high. AIMS: To test whether oral pH modified release budesonide (3 x 1 mg/day)
      reduces the relapse rate and to identify patient subgroups with an increased risk
      of relapse. METHODS: In a multicentre, randomised, double blind study, 179
      patients with steroid induced remission of Crohn's disease received either 3 x 1
      mg budesonide (n = 84) or placebo (n = 95) for one year. The primary study aim
      was the maintenance of remission of Crohn's disease for one year. RESULTS:
      Patient characteristics at study entry were similar for both groups. The relapse
      rate was 67% (56/84) in the budesonide group and 65% (62/95) in the placebo
      group. The relapse curves in both groups were similar. The mean time to relapse
      was 93.5 days in the budesonide group and 67.0 days in the placebo group. No
      prognostic factors allowing prediction of an increased risk for relapse or
      definition of patient subgroups who derived benefit from low dose budesonide were
      found. Drug related side effects were mild and no different between the
      budesonide and the placebo group. CONCLUSION: Oral pH modified release budesonide
      at a dose of 3 x 1 mg/day is not effective for maintaining steroid induced
      remission in Crohn's disease.

PMID- 9616310
TI  - Controlled trial of antituberculous chemotherapy in Crohn's disease: a five year
      follow up study.
AB  - BACKGROUND: It has been suggested that Mycobacterium paratuberculosis is the
      cause of Crohn's disease. In a previous report the immediate effect of two years
      treatment with antituberculous chemotherapy showed no clinical benefit. AIMS: To
      assess both the immediate and longer term effect of treatment on the disease.
      METHODS: Patients were followed for five years from their date of entry to the
      study. One hundred and thirty patients entered the initial study, and of these
      111 (81%) were followed regularly. RESULTS: Overall, there was no evidence of
      consistent benefit or disadvantage from antituberculous chemotherapy in any of
      the assessments made, including the number of acute relapses, surgical episodes,
      hospital admissions, disease activity, blood tests, or medication required for
      Crohn's disease during the follow up period. CONCLUSION: The absence of any
      benefit at the end of the initial two year trial period, and during the three
      year subsequent follow up, fails to support the hypothesis that mycobacteria play
      an important part in the pathogenesis of Crohn's disease, or that antituberculous
      chemotherapy may be of benefit.

PMID- 9616311
TI  - Altered vagal and intestinal mechanosensory function in chronic unexplained
      dyspepsia.
AB  - BACKGROUND: Abnormal visceral mechanosensory and vagal function may play a role
      in the development of functional gastrointestinal disorders. AIMS: To assess
      whether vagal efferent and afferent function is linked with small intestinal
      mechanosensory function. METHODS: In seven patients with functional dyspepsia,
      six patients with a history of Billroth I gastrectomy and/or vagotomy, and seven
      healthy controls, intestinal perception thresholds were tested by a randomised
      ramp distension procedure performed with a barostat device. On a separate day, an
      insulin hypoglycaemia test was performed to assess the plasma levels of
      pancreatic polypeptide (PP) in response to hypoglycaemia, as a test of efferent
      vagal function. RESULTS: First perception of intestinal balloon distension
      occurred at significantly lower pressures in patients with functional dyspepsia
      (median 19.3, range 14.7-25.3 mm Hg) compared with healthy controls (median 26.0,
      range 21.7-43.7 mm Hg, p < 0.01). Sensory thresholds were significantly lower in
      patients after gastrectomy (median 12.2, range 8.0-14.7 mm Hg, p < 0.05 versus
      all others). In healthy controls and patients with functional dyspepsia, insulin
      hypoglycaemia significantly (p < 0.001) increased plasma PP levels. However, only
      two out of seven patients with functional dyspepsia had a more than twofold
      increase in PP values whereas all healthy controls had a more than twofold
      increase in PP levels after insulin hypoglycaemia (p < 0.05). In contrast, there
      was no significant PP response in the gastrectomised patients (median 2%, range 
      10 to +23%). PP responses and visceral sensory thresholds were significantly
      correlated (r = 0.65, p < 0.002). CONCLUSIONS: The diminished PP response after
      insulin hypoglycaemia indicates disturbed efferent vagal function in a subgroup
      of patients with functional dyspepsia. The data also suggest that the intact
      vagal nerve may exert an antinociceptive visceral effect.

PMID- 9616312
TI  - Effects of botulinum toxin A on the sphincter of Oddi: an in vivo and in vitro
      study.
AB  - BACKGROUND: Botulinum toxin A is a potent inhibitor of the release of
      acetylcholine from nerve endings. Local injection of botulinum toxin has recently
      been suggested to be helpful in sphincter of Oddi dyskinesia by decreasing
      sphincter of Oddi pressure. AIMS: To explore the mechanism of action of botulinum
      toxin A on sphincter of Oddi (SO) muscle. METHODS: Four piglets underwent
      duodenoscopy and SO manometry was performed. After obtaining a baseline pressure,
      the SO was injected with normal saline and the experiment repeated after one
      week. The SO was then injected endoscopically with botulinum toxin (40 U) with
      follow up manometry one week later. The sphincter of Oddi was removed from 10
      pigs, cut into three rings, and placed in an organ bath. The force of contraction
      was measured and registered on a polygraph. Rings were stimulated by 70 V (10 Hz,
      0.5 ms) electrical field stimulation for 20 seconds, exogenous acetylcholine (100
      microM), and KCl (125 mM). Botulinum toxin (0.1 U/ml) or atropine (1 microM) was
      added to the incubation medium and the stimulation was repeated. RESULTS: Mean
      basal SO pressure in the pigs remained unchanged after saline injection but
      decreased to about 50% of baseline value following botulinum toxin injection (p =
      0.04). The contractions induced by direct stimulation of SO smooth muscle with
      KCl were not significantly affected by either atropine or botulinum toxin. In all
      rings exogenous acetylcholine induced contractions, which were totally blocked by
      atropine, but not by botulinum toxin. Electrical field stimulation induced
      contractions that were inhibited by both atropine and botulinum toxin.
      CONCLUSION: Botulinum toxin inhibits pig sphincter of Oddi smooth muscle
      contractions by a presynaptic cholinergic mechanism, similar to that described in
      skeletal muscle.

PMID- 9616313
TI  - Effect of a novel prokinetic drug, R093877, on gastrointestinal transit in
      healthy volunteers.
AB  - BACKGROUND: Stronger prokinetic agents which specifically enhance transit in
      different parts of the gut are required. R093877 is a novel 5-HT4 agonist
      prokinetic compound which is chemically related to cisapride but believed to have
      greater effect on colonic activity. AIMS: To evaluate the effects of R093877 on
      bowel function, upper and lower gut transit, visceral sensitivity, and sphincter
      function in healthy volunteers in a double blind, placebo controlled, crossover
      study. METHODS: The study consisted of five consecutive one week periods: no drug
      treatment; active drug treatment with either 1 or 2 mg daily or placebo; washout;
      active drug or placebo; no treatment. Seventeen male subjects maintained a
      detailed dairy of bowel function for the entire study. Orocaecal transit (breath
      hydrogen), whole gut transit (radio-opaque markers), and anorectal function were
      assessed at the end of each of the two treatment periods. Blood testing was
      performed to confirm compliance and for safety analysis. RESULTS: One subject
      withdrew from the study due to side effects while on placebo. Eight subjects
      completed the study on 1 mg and a further eight on 2 mg. Blood testing showed non
      compliance in one subject on the 2 mg dose, and he was excluded from analysis of
      all diary and physiological data. Treatment increased the number of stools per
      week (placebo versus 1 mg, 7.8 versus 13.6, p = 0.003; placebo versus 2 mg, 8.9
      versus 11.3, p = 0.15) and the percentage of loose or watery stools (24.2% versus
      61.5%, p < 0.04; 9.9% versus 40.0%, p < 0.02). Stool frequency and consistency
      reverted to normal immediately after treatment. Treatment shortened orocaecal and
      whole gut transit in all subjects on both doses. Treatment accelerated orocaecal
      (76 versus 51 minutes, p = 0.007; 63 versus 47 minutes, p = 0.07) and whole gut
      (38.2 versus 27.0 hours, p = 0.05; 44.8 versus 24.0 hours, p < 0.04) transit, and
      decreased the number of retained markers ingested 36 hours previously (4.8 versus
      1.8, p = 0.016; 7.0 versus 4.3, p = 0.033). Gut sensitivity to distension and
      electrical stimulation, and anal manometry, were unchanged. Transient headache
      occurred in seven subjects on R093877 and one subject had mild elevation of liver
      aminotransferases which resolved on drug cessation. CONCLUSIONS: R093877 is well
      tolerated by healthy subjects and has a marked and consistent effect on stool
      frequency and consistency, and upper gut and colonic transit. It does not affect
      visceral sensitivity or sphincter function. It holds promise for patients with
      large bowel symptoms or slow gut transit.

PMID- 9616314
TI  - Biofeedback provides long-term benefit for patients with intractable, slow and
      normal transit constipation.
AB  - BACKGROUND: Many patients with idiopathic constipation do not respond to
      conventional medical treatments. Recently biofeedback has been proposed as an
      alternative treatment but the long-term results, and which patients benefit, are
      unknown. Treatment has usually been restricted to patients with normal colonic
      transit and impaired pelvic floor coordination on straining. AIMS: To determine
      the efficacy and long-term outcome of biofeedback treatment in idiopathic
      constipation. METHODS: One hundred consecutive contactable patients who had
      completed a course of biofeedback more than 12 months previously were identified.
      Pretreatment details of bowel function and symptoms, whole gut transit time, and
      anorectal physiological testing, which had been previously prospectively
      collected, were collated. Follow up consisted of structured interview. Sixty five
      per cent had slow transit and 59% had paradoxical pelvic floor contraction on
      straining. RESULTS: Median follow up was 23 months (range 12-44). On long-term
      follow up 55% felt that biofeedback had helped and 57% felt their constipation
      was improved. There was a significant reduction in need to strain, abdominal
      pain, bloating, and oral laxative use. Spontaneous bowel frequency was
      significantly improved by treatment. Patients with slow and normal transit, males
      and females, and those with and without paradoxical contraction of the anal
      sphincter on straining, benefited equally from treatment. Anorectal testing did
      not predict outcome. CONCLUSION: This study suggests that biofeedback is an
      effective long term treatment for the majority of patients with idiopathic
      constipation unresponsive to traditional treatments. Pelvic floor abnormalities
      and transit time should not form selection criteria for treatment.

PMID- 9616315
TI  - Expression of cell membrane complement regulatory glycoproteins along the normal
      and diseased human gastrointestinal tract.
AB  - BACKGROUND/AIMS: Uncontrolled complement activation may be of immunopathological
      importance in inflammatory diseases of the gastrointestinal tract. Expression of
      membrane bound factors that regulate complement activation was therefore studied
      in situ. METHODS: Frozen tissue specimens were obtained from patients with
      Helicobacter pylori gastritis, coeliac disease, Crohn's disease, or ulcerative
      colitis, and from histologically normal controls. Sections were examined by
      immunofluorescence with monoclonal antibodies to protectin (CD59), decay
      accelerating factor (DAF), and membrane cofactor protein (MCP). RESULTS:
      Protectin and MCP were widely expressed in normal and diseased mucosae. MCP was
      generally observed basolaterally on all epithelial cells, whereas apical
      protectin expression was more intense on the epithelium of normal colonic mucosa
      than in the normal duodenum (p = 0.001). Epithelial DAF and to some extent
      protectin were upregulated in gastritis, coeliac disease, and inflammatory bowel
      disease. Areas of the stomach with intestinal metaplasia expressed DAF, unlike
      the adjacent gastric epithelium. Parietal cells of the gastric body expressed
      neither protectin nor DAF. CONCLUSION: Epithelial complement inhibitory molecules
      were expressed differently at various normal gastrointestinal sites and also in
      association with mucosal disease, suggesting variable protective potential. Such
      molecules could play a role in the development of gastric atrophy by protecting
      areas of intestinal metaplasia. Conversely, parietal cells appeared to be
      potentially vulnerable targets for complement attack.

PMID- 9616316
TI  - Apoptosis is a major mode of cell death caused by ischaemia and
      ischaemia/reperfusion injury to the rat intestinal epithelium.
AB  - BACKGROUND AND AIMS: Injuries caused by ischaemia and ischaemia/reperfusion in
      the small intestine have been widely accepted as resulting in necrosis. The aim
      of this study was to ascertain whether apoptosis also occurs. METHODS: Intestinal
      epithelium from rats subjected to ischaemia (15-90 minutes) and
      ischaemia/reperfusion (15 minutes ischaemia followed by 15-75 minutes of
      reperfusion) was studied using histological, immunohistochemical, and molecular
      biological methods as well as FACS. RESULTS: Mucosal injury was induced by both
      ischaemia and ischaemia/reperfusion. Detachment of epithelial cells from the
      villous stroma was an early morphological change indicating mucosal injury. More
      than 80% of the detached cells exhibited characteristic morphological features of
      apoptosis (condensation of chromatin and nuclear fragmentation). The remainder
      demonstrated necrotic features. The apoptotic cells eventually underwent
      spontaneous degeneration with membrane rupture, a process morphologically
      identical to necrosis. DNA fragmentation was also confirmed by
      immunohistochemical methods and agarose gel electrophoresis. CONCLUSION:
      Apoptosis is a major mode of cell death in the destruction of rat small
      intestinal epithelial cells induced by ischaemia and ischaemia/reperfusion
      injury. Disruption of epithelial cell-matrix interactions ("anoikis") may play an
      important part in induction of apoptosis in detached enterocytes.

PMID- 9616317
TI  - Protein transport and processing by human HT29-19A intestinal cells: effect of
      interferon gamma.
AB  - BACKGROUND: The nature of the breakdown products produced in enterocytes during
      epithelial transport of intact proteins may be critical in determining the
      functional consequences of protein absorption. AIM: (a) To measure the
      transepithelial transport of horseradish peroxidase (HRP) and to identify the
      nature of HRP breakdown products released on the basal side of enterocytes and
      (b) to assess the role of interferon gamma (IFN gamma) on HRP transport and
      processing. METHODS: HT29-19A intestinal cells were used to assess
      transepithelial transport of HRP in Ussing chambers, and the nature of breakdown
      products in the basal compartment was analysed by high performance liquid
      chromatography (HPLC). RESULTS: (1) In control conditions, [3H]HRP equivalent
      fluxes (3135 (219) ng/h per cm2; mean (SEM) comprised 50% amino acids, 40%
      peptides, and 10% intact HRP. Steric exclusion HPLC of the breakdown products
      indicated a wide range of molecular masses including a major peptide of about
      1150 Da. Lysosomal aspartyl and thiol proteases were expressed but no HLA-DR
      surface expression was noted, (2) At 48 to 72 hours after IFN gamma stimulation,
      [3H]HRP equivalent fluxes increased significantly (7392 (1433) ng/h per cm2)
      without modification of the relative proportions of amino acids, peptides, and
      intact HRP, and without modification of the distribution of breakdown products in
      HPLC. Lysosomal protease activities were not modified by IFN gamma but HLA-DR
      expression was increased. CONCLUSION: Intestinal cells are able to process HRP
      into peptides potentially capable of stimulating the immune system. IFN gamma
      stimulates the transport and processing of HRP thus increasing the antigenic load
      in the intestinal mucosa.

PMID- 9616318
TI  - Neurotensin receptors: a new marker for human ductal pancreatic adenocarcinoma.
AB  - BACKGROUND/AIMS: New imaging possibilities for early diagnosis of the devastating
      exocrine pancreatic adenocarcinomas would be highly welcome. Recently, pancreatic
      neuroendocrine tumours have been successfully visualised in vivo on the basis of
      their high density of receptors for the regulatory peptide somatostatin.
      Unfortunately, exocrine pancreatic tumours do not express sufficient amounts of
      somatostatin receptors. Therefore over-expression of other regulatory peptide
      receptors in these tumours needs to be found. METHODS: Receptors for the
      regulatory peptide neurotensin were evaluated in vitro by receptor
      autoradiography in 24 ductal pancreatic adenocarcinomas, 20 endocrine pancreatic
      cancers, 18 cases of chronic pancreatitis, and 10 normal pancreatic glands.
      RESULTS: Some 75% of all ductal pancreatic adenocarcinomas, most of them
      differentiated, were neurotensin receptor positive, whereas endocrine pancreatic
      cancers did not express neurotensin receptors. No neurotensin receptors were
      found in chronic pancreatitis or normal pancreatic tissues, including pancreatic
      acini, ducts, and islets. CONCLUSIONS: The selective and high expression of
      neurotensin receptors in ductal pancreatic adenocarcinomas could form the
      molecular basis for potential clinical applications, such as in vivo neurotensin
      receptor scintigraphy for early tumour diagnosis, radiotherapy with radiolabelled
      neurotensin analogues, and chemotherapy with neurotensin receptor antagonists.

PMID- 9616319
TI  - Faecal elastase 1: not helpful in diagnosing chronic pancreatitis associated with
      mild to moderate exocrine pancreatic insufficiency.
AB  - BACKGROUND/AIM: The suggestion that estimation of faecal elastase 1 is a valuable
      new tubeless pancreatic function test was evaluated by comparing it with faecal
      chymotrypsin estimation in patients categorised according to grades of exocrine
      pancreatic insufficiency (EPI) based on the gold standard tests, the secretin
      pancreozymin test (SPT) and faecal fat analysis. METHODS: In 64 patients in whom
      EPI was suspected, the following tests were performed: SPT, faecal fat analysis,
      faecal chymotrypsin estimation, faecal elastase 1 estimation. EPI was graded
      according to the results of the SPT and faecal fat analysis as absent, mild,
      moderate, or severe. The upper limit of normal for faecal elastase 1 was taken as
      200 micrograms/g, and for faecal chymotrypsin 3 U/g stool. Levels between 3 and 6
      U/g stool for faecal chymotrypsin are usually considered to be suspicious for
      EPI. In this study, both 3 and 6 U/g stool were evaluated as the upper limit of
      normal. RESULTS: Exocrine pancreatic function was normal in 34 patients, of whom
      94, 91, and 79% had normal faecal elastase 1 and faecal chymotrypsin levels (< 3
      U/g and < 6 U/g) respectively. Thirty patients had EPI, of whom 53, 37, and 57%
      had abnormal faecal enzyme levels (differences not significant). When EPI was
      graded as mild, moderate, or severe, 63% of patients had mild to moderate EPI,
      and 37% had severe EPI. In the latter group, between 73 and 91% of patients had
      abnormal faecal enzymes. In the group with mild to moderate EPI, abnormal test
      results were obtained for both faecal enzymes in less than 50% of the patients
      (differences not significant). Some 40% of the patients had pancreatic
      calcifications. There were no significant differences for either faecal enzyme
      between the two groups with and without pancreatic calcifications. In 62% of the
      patients who underwent an endoscopic retrograde cholangiopancreatography (ERCP),
      abnormal duct changes were found. Again, there were no significant differences
      for either faecal enzyme between the two groups with abnormal and normal ERCP.
      CONCLUSION: Estimation of faecal elastase 1 is not distinctly superior to the
      traditional faecal chymotrypsin estimation. The former is particularly helpful
      only in detecting severe EPI, but not the mild to moderate form, which poses the
      more frequent and difficult clinical problem and does not correlate significantly
      with the severe morphological changes seen in chronic pancreatitis.

PMID- 9616321
TI  - Uptake, yield of neoplasia, and adverse effects of flexible sigmoidoscopy
      screening.
AB  - BACKGROUND: A multicentre randomised controlled trial to evaluate screening by
      "once only" flexible sigmoidoscopy (FS) for prevention of bowel cancer is in
      progress. AIMS: To pilot the trial protocol examining rates of attendance, yield
      of neoplasia, and adverse effects. SUBJECTS: A total of 3540 subjects aged 55-64
      years in Welwyn Garden City (WGC) and 19,706 in Leicester (LE). METHODS: Subjects
      responding positively to an "interest in screening" questionnaire were randomised
      to invitation for screening or control arms. Small polyps were removed during
      screening. Colonoscopy was undertaken for high risk polyps (more than two
      adenomas, size at least 1 cm, villous histology, severe dysplasia, or
      malignancy). The remainder were discharged. RESULTS: In WGC and LE respectively,
      59% and 61% indicated an interest in screening, of which 74% and 75% attended.
      Adenomas were detected in 10% and 9%, respectively, and cancers in 7 per 1000 (in
      both centres), 55% at Dukes's stage A. The colonoscopy referral rate was 6% in
      both centres. Mild, short lived bleeding occurred in 3%. One person died
      following surgery. CONCLUSIONS: Compliance rates, yield of adenomas, and referral
      rate for colonoscopy were as expected, but cancer detection rates were higher.
      Adverse effects following sigmoidoscopy or colonoscopy were mild and transient,
      but there was one postoperative death. A randomised trial is necessary to
      evaluate fully the risks and benefits of this intervention.

PMID- 9616320
TI  - Persistent systemic inflammatory response after stent insertion in patients with
      malignant bile duct obstruction.
AB  - BACKGROUND: Surgery in patients with malignant bile duct obstruction is
      associated with high postoperative morbidity and mortality. Tumour necrosis
      factor alpha (TNF-alpha) plays a key role in the pathogenesis of these
      complications. AIMS: To determine the effect of biliary drainage on plasma
      concentrations of TNF-alpha, its soluble circulating receptors (sTNFr), and other
      proinflammatory cytokines. METHODS: Plasma concentrations of TNF-alpha, sTNFr
      P75, interleukin 6 (IL-6), and IL-1 alpha were measured in 25 patients with
      malignant bile duct obstruction before and after endoscopic stent insertion.
      RESULTS: Mean serum bilirubin was 157 mumol/l before stent insertion and 35.2
      mumol/l one week post stent insertion. There was complete relief of jaundice in
      77% of patients by four weeks. Plasma concentrations of TNF-alpha and IL-1 alpha
      were below the detection limit of the assays in all samples. Median plasma sTNFr
      P75 in the cancer patients was 960 ng/l (range 400-6600), before stent insertion
      and remained unchanged at one and four weeks after stenting. Plasma sTNFr-P75 in
      cancer patients was significantly higher (p < 0.01) than in healthy controls (250
      (200-650) ng/l). Before stent insertion, plasma IL-6 concentrations were
      detectable (above 5 ng/l) in 17 (68%) patients. After relief of biliary
      obstruction IL-6 levels fell from a prestent median of 13.2 to less than 5 ng/l
      at one week after stent insertion. Plasma concentrations of IL-6 were
      undetectable in 76% of patients at this time. CONCLUSION: Activation of the
      TNF/sTNFr complex is unchanged after biliary drainage in patients with malignant
      bile duct obstruction. This may explain why preoperative drainage does not
      influence the high morbidity and mortality associated with surgery in these
      patients.

PMID- 9616322
TI  - A rapid method of haplotyping HFE mutations and linkage disequilibrium in a
      Caucasoid population.
AB  - BACKGROUND: HFE mutations are associated with hereditary haemochromatosis.
      However, a simple method capable of demonstrating the cis/trans arrangement of
      alleles is lacking, and linkage disequilibrium between HFE alleles and classic
      HLA loci is unknown. These are important issues as the pathogenic role of the
      mutations is not known. AIMS: To develop a simple method of genotyping HFE
      mutations suitable for clinical use in addition to large disease studies.
      PATIENTS: A total of 330 Caucasoid cadaveric organ donor controls were examined.
      Ten individuals previously HLA-H genotyped by polymerase chain reaction using
      restriction fragment length polymorphism (PCR-RFLP) were also examined to
      validate the method. METHODS: A simple polymerase chain reaction using sequence
      specific primers (PCR-SSP) capable of haplotyping the mutations was developed.
      HFE allele and haplotype frequencies and linkage disequilibrium with eight HLA
      class I and II loci were examined in the control population. RESULTS: 27% and
      19.7% of patients were positive for the 63D and 282Y alleles, respectively. No
      chromosome carried both 63D and 282Y. Linkage disequilibrium between 282Y and HLA
      A*03 was confirmed, but was not straightforward: some A*03-associated alleles
      (DRB1*15, DQB1*06), but not all (B*07, Cw*0702), were associated with 282Y.
      CONCLUSIONS: Linkage disequilibrium data suggest that an HLA-B*07 containing
      haplotype contains an element affording protection from haemochromatosis and may
      suggest the timing of the founder 282Y mutation.

PMID- 9616323
TI  - Clinical significance of intrahepatic hepatitis C virus levels in patients with
      chronic HCV infection.
AB  - BACKGROUND: The clinical significance of a single assessment of circulating
      hepatitis C virus (HCV) RNA and its relation to the level of intrahepatic HCV RNA
      remains unclear. AIMS: To investigate the relation between intrahepatic HCV
      levels and clinicopathological characteristics of chronic HCV infection.
      PATIENTS: Ninety eight consecutive patients with chronic HCV infection were
      studied; none had received alpha interferon therapy. Of these, 12 patients were
      repeatedly negative for HCV RNA in serum by reverse transcriptase polymerase
      chain reaction (RT-PCR). METHODS: After diagnostic laparoscopy and liver biopsy,
      semiquantitative analysis of intrahepatic HCV RNA levels was carried out by
      limiting dilution of HCV cDNA. HCV genotypes were assessed in 96 patients by
      restriction fragment length polymorphism analysis of HCV cDNA. RESULTS: Ten out
      of 12 patients who were RT-PCR negative for HCV RNA in serum were RT-PCR positive
      in liver; however, this group had a significantly lower intrahepatic HCV level
      and serum aminotransferase level than the remaining 86 patients. Histological
      severity (cirrhosis: n = 10); histological activity index; HCV genotype (genotype
      1: n = 41; genotype 2: n = 12; genotype 3: n = 36; genotype 4: n = 7); mode of
      infection (intravenous drug abuse: n = 58; post-transfusion: n = 10;
      haemophiliac: n = 4; sporadic: n = 26) and alcohol abuse did not affect the
      intrahepatic virus level. There was no correlation between patient age, duration
      of infection, and intrahepatic HCV level. CONCLUSIONS: Intrahepatic virus levels
      were not determined by host factors (age of patient, mode or duration of
      infection) or by virus factors (HCV genotype). Repeatedly negative RT-PCR for HCV
      RNA in serum does not indicate absence of HCV from the liver.

PMID- 9616324
TI  - Acute liver failure secondary to hepatic infiltration: a single centre experience
      of 18 cases.
AB  - BACKGROUND: Acute liver failure (ALF) secondary to malignant infiltration of the
      liver is rare and is diagnosed often only after death. AIMS: To determine
      diagnostic factors and particular clinical patterns of illness. METHODS: Review
      of case notes from all patients with ALF secondary to hepatic infiltration
      admitted to this unit over an 18 year period (1978-1995). RESULTS: From a total
      of 4020 admissions, 18 patients were identified with ALF attributable to hepatic
      infiltration. Mean age was 40.7 years. Aetiology was non-Hodgkin's lymphoma in
      nine patients, Hodgkin's disease in three, infiltrative metastatic carcinoma in
      four, and haemophagocytosis with no precipitant cause in two cases. Prodromal
      symptoms were non-specific, but occurred at least two to four weeks before onset
      of ALF, making the presence of such symptoms of value in differential diagnosis
      of the cause of ALF. Clinical examination and investigations were unhelpful in
      distinguishing these cases from more usual causes of ALF. Usually, the clinical
      course was of rapid deterioration and death from multiorgan failure, and only one
      patient survived. Diagnosis was made during life in 15 patients. Histology showed
      evidence of widespread hepatocellular necrosis, with diffuse infiltration by
      tumour cells rather than focal cellular aggregation. CONCLUSIONS: Only with
      accurate histological diagnosis from liver biopsy and institution of specific
      therapy early in the management of such patients will the best chance of recovery
      be achieved. In every case of ALF with prodromal symptoms or abnormal imaging,
      hepatic histology should be obtained by liver biopsy as soon as possible to
      diagnose infiltrative hepatic disease.

PMID- 9616326
TI  - Cleaning and disinfection of equipment for gastrointestinal endoscopy. Report of
      a Working Party of the British Society of Gastroenterology Endoscopy Committee.
AB  - Two per cent glutaraldehyde is the most commonly used disinfectant in endoscopy
      units within the UK. Unfortunately adverse reactions to glutaraldehyde are common
      among endoscopy personnel and the Health and Safety Commission has recommended
      substantial reductions in atmospheric levels of glutaraldehyde in order to comply
      with the Control of Substances Hazardous to Health Regulations, 1994. The Working
      Party addressed ways of eliminating or minimising exposure to glutaraldehyde in
      endoscopy units by reviewing alternative disinfectants and the use of automated
      washer/disinfectors. Alternatives to glutaraldehyde must be at least as
      microbicidal as glutaraldehyde, non-irritating and compatible with endoscope
      components and decontamination equipment. Peracetic acid is a highly effective
      disinfectant and may be a suitable alternative to glutaraldehyde. Peracetic acid
      has a vinegary-like odour and is claimed to be less irritating than
      glutaraldehyde. Experience with this agent remains relatively limited and the
      Working Party recommends that peracetic acid should be used in sealed or exhaust
      ventilated facilities until further experience is obtained. It is considerably
      more expensive than glutaraldehyde, is less stable and large volumes have to be
      stored. It causes cosmetic (but not functional) damage to endoscopes and is not
      compatible with some washer/ disinfectors. Chlorine dioxide is a powerful
      oxidising agent and highly effective as a disinfectant. Once activated it must be
      stored in sealed containers with little head space. Fumes cause irritation and
      sealed or exhaust ventilated facilities are necessary. The agent may damage some
      metallic and polymer components of endoscopes and automated washer/disinfectors
      and compatibility should be established with equipment manufacturers before the
      agent is used. Other disinfectants such as peroxygen compounds and quaternary
      ammonium derivatives are less suitable because of unsatisfactory mycobactericidal
      and/or virucidal activity, or incompatibility with endoscopes and automated
      washer/disinfectors. Alcohol is effective but, on prolonged contact, is damaging
      to lens cements. It is also flammable and therefore unsuitable for use in large
      quantities in automated systems. Superoxidised water (Sterilox) is an
      electrochemical solution (anolyte) containing a mixture of radicals with strong
      oxidising properties. It is highly microbicidal when freshly generated, provided
      items are thoroughly clean and strict generation criteria are met--that is,
      current, pH, redox potential. It seems to be safe for users and provided field
      trials substantiate laboratory efficacy tests, and the agent is non-damaging, it
      too may become an alternative to glutaraldehyde. When 2% glutaraldehyde is used
      for manual and automated disinfection, 10 minutes' immersion is recommended for
      endoscopes before the session and between patients. This will destroy vegetative
      bacteria and viruses (including hepatitis B virus (HBV) and HIV). A five minute
      contact period is recommended for 0.35% peracetic acid and for chlorine dioxide
      (1100 ppm av ClO2), but if immersed for 10 minutes sporicidal activity will also
      be achieved. At the end of each session 20 minutes' immersion in glutaraldehyde
      or five minutes in peracetic acid or chlorine dioxide is recommended.
      Microbiological studies show that 20 minutes of exposure to 2% glutaraldehyde
      destroys most organisms, including Mycobacterium tuberculosis. The Working Party
      concludes therefore that immersion of the endoscope in 2% glutaraldehyde for 20
      minutes is sufficient for endoscopy involving patients with AIDS and other
      immunodeficiency states or pulmonary tuberculosis. Similarly, 20 minutes'
      immersion is recommended at the start of the list and between cases for
      endoscopic retrograde cholangiopancreatography (ERCP) when high level
      disinfection is required. Cleaning and disinfection of endoscopes should be
      undertaken by trained staff in a dedicated room. Thorough cleaning with detergent

PMID- 9616325
TI  - Gastrin, gastrin receptors and colorectal carcinoma.

PMID- 9616327
TI  - When is a coeliac a coeliac?

PMID- 9616328
TI  - Gastric bacterial overgrowth is a cause of false positive diagnosis of
      Helicobacter pylori infection using 13C urea breath test.

PMID- 9616329
TI  - The Maastricht Consensus Report. Treating young dyspeptic patients.

PMID- 9616330
TI  - The Maastricht Consensus Report. Functional dyspepsia in the young.

PMID- 9616331
TI  - The Maastricht Consensus Report. Dual publication.

PMID- 9616332
TI  - Efficacy of ranitidine bismuth citrate (RBC) dual and triple therapies for the
      eradication of Helicobacter pylori.

PMID- 9616333
TI  - Management of polycythaemia in adults with cyanotic congenital heart disease.

PMID- 9616334
TI  - Hypertrophic cardiomyopathy: is there a role for amiodarone?

PMID- 9616335
TI  - Dealing with in-stent restenosis.

PMID- 9616336
TI  - Determination of prestenotic flow volume using an automated method based on
      colour Doppler imaging for evaluating orifice area by the continuity equation:
      validation in a pulsatile flow model.
AB  - OBJECTIVE: To evaluate, in a pulsatile flow model simulating flow conditions in
      valvar stenoses, whether accurate determination of orifice area can be achieved
      by the continuity equation using automated determination of flow volumes based on
      spatiotemporal integration of digital colour Doppler flow velocities. METHODS: A
      method for automated determination of flow volumes which takes into account the
      velocity distribution across a region of interest was examined using flow through
      a tube and various restrictive outlet orifices with areas ranging between 0.2 and
      3.1 cm2. The sampling rectangle of the Doppler method was positioned proximal to
      the obstructions within the flow convergence zone for evaluating prestenotic flow
      volume. Stenotic jet velocities were recorded by continuous wave Doppler to
      obtain the integral under the velocity curve. Prestenotic flow volume was then
      divided by the velocity integral to calculate functional orifice area according
      to the continuity equation. RESULTS: The presence of parabolically shaped
      velocity profiles across the prestenotic region was demonstrated by the Doppler
      method. Excellent agreement was found between prestenotic flow volumes measured
      by the Doppler technique and actual values (r = 0.99, SEE = 1.35 ml, y = 0.99x
      0.24). Use of the continuity equation led to a close correlation, with a
      systematic underestimation of geometric orifice sizes. Correction of Doppler data
      for flow contraction yielded an excellent agreement with actual orifice areas.
      CONCLUSIONS: The study validated the accuracy of a Doppler method for automated
      determination of flow volumes for quantifying orifice area by the continuity
      equation. Prestenotic flow volume and functional orifice area could be evaluated
      reliably in the presence of non-flat velocity profiles. Thus the method
      contributes to the non-invasive assessment of valvar stenoses.

PMID- 9616337
TI  - Stamps in cardiology. Cardiopulmonary resuscitation.

PMID- 9616338
TI  - Prognostic value of non-sustained ventricular tachycardia and the potential role
      of amiodarone treatment in hypertrophic cardiomyopathy: assessment in an
      unselected non-referral based patient population.
AB  - BACKGROUND: Amiodarone has been reported to reduce the likelihood of sudden death
      in patients with hypertrophic cardiomyopathy (HCM). However, data regarding the
      clinical course in HCM have traditionally come from selected referral populations
      biased toward assessment of high risk patients. AIMS: To evaluate antiarrhythmic
      treatment for sudden death in an HCM population not subject to tertiary referral
      bias, closely resembling the true disease state present in the community.
      METHODS: Cardiovascular mortality was assessed in relation to the occurrence of
      non-sustained ventricular tachycardia (NSVT) on 24 or 48 hour ambulatory Holter
      recording, a finding previously regarded as a marker for sudden death,
      particularly when the arrhythmia was frequent, repetitive or prolonged. 167
      consecutive patients were analysed by multiple Holter ECG recordings (mean (SD)
      157 (129) hours) and followed for a mean of 10 (5) years. Only patients with
      multiple repetitive NSVT were treated with amiodarone, and in relatively low.
      doses (220 (44) mg/day). RESULTS: Nine HCM related deaths occurred: 8 were the
      consequence of congestive heart failure, but only 1 was sudden and unexpected.
      Three groups of patients were segregated based on their NSVT profile: group 1 (n
      = 39), multiple (> or = 2 runs) and repetitive bursts (on > or = 2 Holters) of
      NSVT, or prolonged runs of ventricular tachycardia, included 4 deaths due to
      heart failure; group 2 (n = 38), isolated infrequent bursts of NSVT, included 1
      sudden death; group 3 (n = 90), without NSVT, included 4 heart failure deaths.
      Kaplan-Meier survival analysis showed no significant differences in survival
      between the three groups throughout follow up. CONCLUSIONS: In an unselected
      patient population with HCM, isolated, non-repetitive bursts of NSVT were not
      associated with adverse prognosis and so this arrhythmia does not appear to
      justify chronic antiarrhythmic treatment. Amiodarone, administered in relatively
      low doses, did not carry an independent and additive risk for cardiac mortality.
      Amiodarone may have contributed to the absence of sudden cardiac death in
      patients believed to be at higher risk because of multiple repetitive NSVT.

PMID- 9616339
TI  - Long-term survival effect of metoprolol in dilated cardiomyopathy. The SPIC
      (Italian Multicentre Cardiomyopathy Study) Group.
AB  - OBJECTIVE: To evaluate the additive effect of metoprolol treatment on long-term
      incidence of fatal and non-fatal cardiac events in idiopathic dilated
      cardiomyopathy. DESIGN: 586 patients with idiopathic dilated cardiomyopathy were
      prospectively enrolled in a multicentre registry and followed up for a mean (SD)
      of 52 (32) months. Metoprolol, carefully titrated to the maximum tolerated dose,
      was added to conventional heart failure treatment in 175 patients. RESULTS:
      Survival and transplant-free survival at seven years were significantly higher in
      the 175 metoprolol treated patients than in the remaining 411 on standard
      treatment (81% v 60%, p < 0.001, and 69% v 49%, p < 0.001, respectively). By
      multivariate analysis, metoprolol independently predicted survival and transplant
      free survival (relative risk reduction values for all cause mortality and
      combined mortality or transplantation 51% (95% confidence interval 21% to 69%), p
      = 0.002, and 34% (5% to 53%), p = 0.01, respectively). New York Heart Association
      class, left ventricular end diastolic diameter, and pulmonary wedge pressure were
      also predictive. Seven year survival (80% v 62%, p = 0.004) and transplant-free
      survival (68% v 51%, p = 0.005) were significantly higher in 127 metoprolol
      treated cases than in 127 controls selected from the entire control cohort and
      appropriately matched. Metoprolol was associated with a 30% reduction in all
      cause mortality (7% to 48%, p = 0.015) and a 26% reduction in mortality or
      transplantation (7% to 41%, p = 0.009). CONCLUSIONS: The addition of metoprolol
      to standard heart failure treatment, including angiotensin converting enzyme
      inhibitors, was effective in the long-term, reducing both all cause mortality and
      transplantation in patients with idiopathic dilated cardiomyopathy.

PMID- 9616340
TI  - Analysis of deaths while waiting for cardiac surgery among 29,293 consecutive
      patients in Ontario, Canada. The Steering Committee of the Cardiac Care Network
      of Ontario.
AB  - OBJECTIVES: To assess death rates among patients waiting for cardiac valve
      surgery or isolated coronary artery bypass surgery (CABG), and to determine
      independent risk factors for death while waiting for isolated CABG. DESIGN:
      Prospective cohort analysis based on an inclusive registry. SETTING: Nine cardiac
      surgical units in Ontario, Canada. PATIENTS: 29,293 consecutive patients
      scheduled for cardiac surgery between October 1991 and June 1995. MAIN OUTCOME
      MEASURES: Death rates while waiting for surgery were determined among patients
      scheduled for isolated CABG, isolated valve surgery, or combined procedures.
      Predictors of death among patients with isolated CABG were determined from
      multivariate analysis. RESULTS: There were 141 deaths (0.48%) among 29,293
      patients. Adjusting for age, sex, and waiting time, patients waiting for valve
      surgery had a significantly increased risk of death compared with patients
      waiting for CABG alone (adjusted odds ratio 1.88, 95% confidence interval (CI)
      1.23 to 2.88, p = 0.004). Results were similar for patients waiting for combined
      valve and CABG procedures compared with those who were waiting for isolated CABG.
      Independent risk factors for death while waiting for isolated CABG included:
      impaired left ventricular function (odds ratio 2.47, 95% CI 1.59 to 3.84, p <
      0.001); advancing age (for each decade, odds ratio 1.41, 95% CI 1.10 to 1.80, p =
      0.007); male sex (odds ratio 1.95, 95% CI 1.00 to 3.81, p = 0.05); and waiting
      longer than the maximum time recommended in Canadian guidelines for a patient's
      clinical profile (odds ratio 1.59, 95% CI 1.01 to 2.51, p = 0.044). After scaling
      waiting time to surgery or death continuously in days, the same predictors
      emerged. CONCLUSIONS: Patients waiting for valve surgery have a higher risk of
      death than patients waiting for isolated CABG. Guidelines to promote safer and
      fairer queuing for non-CABG cardiac surgery are needed. Shorter waiting lists,
      better compliance with existing guidelines, and guideline revisions to upgrade
      patients with left ventricular dysfunction could generate additional reductions
      in the already low risk of death for patients waiting for isolated CABG.

PMID- 9616341
TI  - Predicting operative risk for coronary artery surgery in the United Kingdom: a
      comparison of various risk prediction algorithms.
AB  - OBJECTIVE: To compare the ability of four risk models to predict operative
      mortality after coronary artery bypass graft surgery (CABG) in the United
      Kingdom. DESIGN: Prospective study. SETTING: Two cardiothoracic centres in the
      United Kingdom. SUBJECTS: 1774 patients having CABG. MAIN OUTCOME MEASURES: Risk
      factors were recorded for all patients, along with in-hospital mortality.
      Predicted mortality was derived from the American Society of Thoracic Surgeons
      (STS) risk program, Ontario Province risk score (PACCN), Parsonnet score, and the
      UK Society of Cardiothoracic Surgeons risk algorithm. RESULTS: There were
      significant differences (p < 0.05) between the British and American populations
      from which the STS risk algorithm was derived with respect to most variables. The
      observed mortality in the British population was 3.7% (65 of 1774). The mean
      predicted mortality by STS score, PACCN, Parsonnet score, and UK algorithms were
      1.1%, 1.6%, 4.6%, and 4.7% respectively. The overall predictive ability of the
      models as measured by the area under the receiver operating characteristic curve
      were 0.64, 0.60, 0.73, and 0.75, respectively. CONCLUSIONS: There are differences
      between the British and American populations for CABG and the North American
      algorithms are not useful for predicting mortality in the United Kingdom. The UK
      Society of Cardiothoracic Surgeons algorithm is the best of the models tested but
      still only has limited predictive ability. Great care must be exercised when
      using methods of this type for comparisons of units and surgeons.

PMID- 9616342
TI  - Circumstances and causes of out-of-hospital cardiac arrest in sudden death
      survivors.
AB  - OBJECTIVE: To study the circumstances and medical profile of out-of-hospital
      sudden cardiac arrest (SCA) patients in whom resuscitation was attempted by the
      ambulance service, and to identify causes of SCA in survivors and factors that
      influence resuscitation success rate. METHODS: During a five year period (1991
      95) all cases of out-of-hospital SCA between the ages of 20 and 75 years and
      living in the Maastricht area in the Netherlands were studied. Information was
      gathered about the circumstances of SCA, as well as medical history for all
      patients in whom resuscitation was attempted by the ambulance personnel. Causes
      of SCA in survivors were studied and logistic regression analysis was performed
      to identify factors associated with survival. RESULTS: Of 288 SCA patients in
      whom cardiopulmonary resuscitation (CPR) and advanced life support were applied,
      47 (16%) were discharged alive from the hospital. Their mean (SD) age was 58 (11)
      years, 37 (79%) were men, and 24 (51%) had a history of cardiac disease. Acute
      myocardial infarction was diagnosed in 24 (51%) of the survivors; seven with and
      17 without a history of cardiac disease. Ventricular fibrillation (VF) or
      ventricular tachycardia (VT) as the first documented rhythm was significantly
      positively associated with survival (odds ratio (OR) 5.7, 95% confidence interval
      (CI) 2.1 to 15.9). A time interval of less than four minutes between the moment
      of collapse and the start of resuscitation, and an ambulance delay time of less
      than eight minutes were significantly positively associated with survival (OR
      3.3, 95% CI 1.3 to 8.6, and OR, 3.6, 95% CI 1.3 to 10.5, respectively). A history
      of cardiac disease was negatively associated with survival (OR 0.46, 95% CI 0.21
      to 0.98). CONCLUSIONS: Acute myocardial infarction was the underlying mechanism
      of SCA in most of the survivors, especially in those without a history of cardiac
      disease. CPR within four minutes, an ambulance delay time less than eight
      minutes, and VT or VF diagnosed by the paramedics were positively associated with
      success.

PMID- 9616343
TI  - Long-term follow up of patients with endomyocardial fibrosis: effects of surgery.
AB  - AIMS: To determine the long-term outcome of patients with endomyocardial fibrosis
      and to compare echocardiographic and haemodynamic data before and after
      ventricular endocardial resection. PATIENTS: Seventeen patients (11 women and six
      men; mean age 35.5 years) diagnosed with endomyocardial fibrosis at the
      University Hospital in Zurich, Switzerland from 1971 to 1995. Twelve patients
      (70%) had partial obliteration of both ventricles and in five patients (30%) the
      fibrotic lesions were limited to the left ventricle. METHODS: Fourteen of the 17
      patients had surgical resection: fibrosis was resected from both ventricles in
      five patients and from the left ventricle only in nine patients. Ten patients had
      mitral valve replacement and two had tricuspid valve replacement. Left ventricle
      endocardial resection was done without reconstruction or replacement of the
      atrioventricular valve in three patients. Preoperative and postoperative
      echocardiographic data were available for 11 patients and haemodynamic data for
      six patients. Patients were followed up for 0.4-19 years (mean 8.6). RESULTS:
      Preoperatively four patients were NYHA functional class IV and 10 were class III;
      postoperatively one patient was class III, seven class II, and six class I.
      Preoperatively, echocardiography showed obliteration of the left ventricular apex
      and inflow tract in all patients, which decreased or disappeared after surgery.
      Left ventricular end diastolic pressure decreased from 25 mm Hg before surgery to
      14 mm Hg after successful resection of the fibrosis. Left ventricular and
      diastolic volume (normal 93 (17) ml/m2) increased from 65 ml/m2 to 97 ml/m2 (p <
      0.05) after surgery. Ejection fraction was normal preoperatively (57%) and
      decreased slightly (52%) after surgery. One patient died five months after
      surgery from heart failure. Four surgically treated patients died during the
      follow up period: one each from systolic dysfunction, recurrence of
      endomyocardial fibrosis, pneumonia, and food poisoning. Overall survival was 65%
      at five years and 59% at 10 years; the survival rates of the operated patients
      was 72% and 68%, respectively. Only one of the medically treated patients
      survived longer than three years from diagnosis. CONCLUSIONS: Endomyocardial
      fibrosis is a rare disease in European countries and is found mainly in women.
      The clinical picture is characterised by severe congestive heart failure but
      heart size is only moderately increased. Systolic performance is normal or only
      slightly depressed despite severe restriction to filling, atrioventricular valve
      regurgitation or both. Partial obliteration of the right and/or left ventricle
      may be detected by echocardiography. Endocardial resection with atrioventricular
      valve replacement is the treatment of choice with appreciable postoperative
      improvement and 10 year survival of approximately 70%.

PMID- 9616344
TI  - Occlusion of Fontan fenestrations using the Amplatzer septal occluder.
AB  - OBJECTIVE: To evaluate the efficacy and safety of the Amplatzer septal occluder
      device for occlusion of Fontan fenestrations. SUBJECTS: Five children aged 5-10
      years who had undergone a fenestrated Fontan operation. SETTING: Tertiary
      paediatric cardiology centre. METHODS: Each patient had right and left heart
      catheterisation to assess haemodynamic suitability for fenestration closure.
      Sizing of the defect was achieved with a balloon wedge catheter and
      transoesphageal echocardiography. Transcatheter occlusion of the fenestration was
      accomplished using a 4 mm device in three patients, and 5 mm or 9 mm devices in
      the other two patients. Residual shunting following occlusion was assessed using
      angiography and echocardiography. RESULTS: 100% occlusion rate of the
      fenestration was achieved in all patients. No complications or device failures
      were seen during the three month follow up period. CONCLUSION: The Amplatzer
      septal occluder device is safe, and effectively occludes the Fontan fenestration.

PMID- 9616345
TI  - Outcome after prenatal diagnosis of the hypoplastic left heart syndrome.
AB  - OBJECTIVE: To derive accurate survival figures in the current surgical era for
      counselling in early pregnancy after the diagnosis of fetal hypoplastic left
      heart syndrome. SETTING: A tertiary referral centre for paediatric cardiology and
      cardiac surgery. DESIGN: A retrospective study of the outcome in all cases of
      hypoplastic left heart syndrome presenting in fetal life between mid-1993 and the
      end of 1996. PATIENTS: The diagnosis was made in 30 fetuses. In four of 12
      identified before 24 weeks' gestation the mothers chose to terminate the
      pregnancy. There was an intention to treat in 24 of the remaining fetuses. MAIN
      OUTCOME MEASURE: Survival to six months of postnatal life. RESULTS: Of the 24
      infants, five were not offered Norwood stage 1 because of trisomy 18 (n = 2),
      unfavourable cardiac anatomy (n = 2), or neurological impairment (n = 1). One
      further infant did not survive to cardiac surgery after gastrointestinal surgery.
      Of the remaining 18 patients, eight had features that were considered to increase
      the risk of surgical repair. Of the 18 patients who underwent Norwood stage 1,
      there were nine survivors. There was a survival rate of 70% in infants undergoing
      surgery with no complicating features, a 50% survival of the all surgical
      candidates, and 37.5% survival from an intention to treat position. CONCLUSIONS:
      At the initial diagnosis of fetal hypoplastic left heart syndrome, the overall
      survival appears to be less than 40%. Evaluation must include detailed
      extracardiac and intracardiac assessment to predict the risks of surgical
      treatment. Prenatal counselling can be modified as pregnancy advances, depending
      on the detection or exclusion of complicating factors.

PMID- 9616346
TI  - Prevalence of ventricular preexcitation in Japanese schoolchildren.
AB  - BACKGROUND: Wolff-Parkinson-White syndrome is thought to be a congenital disease,
      however, its exact prevalence is not known. This may be because of the
      intermittent activity of accessory pathways in some cases and fluctuations in
      autonomic tone. AIMS: To investigate the prevalence of ventricular preexcitation
      by electrocardiography and reported symptoms in each school age child in
      Yamanashi prefecture. METHODS: From 1994 to 1996, answers to a questionnaire,
      results of physical examination, and electrocardiography were obtained from all
      schoolchildren in Yamanashi prefecture (n = 92,161; total population 880,000) on
      admission to elementary school (age 6 to 7 years, n = 28,395), junior high school
      (age 12 to 13 years, n = 31,206), and high school (age 14 to 15 years, n =
      32,837). RESULTS: Elementary and junior high school students had a significantly
      lower prevalence of preexcitation than high school students (0.073% and 0.070% v
      0.174%, p < 0.001). The prevalence of left free wall pathway was highest in high
      school students (n = 27) compared with elementary (n = 6) and junior high school
      students (n = 5) (p < 0.005). The only symptom noted in the answers to the
      questionnaire was palpitations. The symptomatic cases were more frequent in high
      school (n = 13) than in elementary (n = 1) and junior high school (n = 2)
      children, but not significantly. No student with preexcitation had associated
      heart disease or family history of Wolff-Parkinson-White syndrome or sudden
      death. CONCLUSIONS: The prevalence of preexcitation in younger schoolchildren was
      less frequent than previously reported. The prevalence of preexcitation and left
      free wall pathways increased with age. The symptoms were few and there was no
      significant morbidity.

PMID- 9616347
TI  - The transseptal approach for ablation of cardiac arrhythmias: experience of 104
      procedures.
AB  - OBJECTIVE: To report retrospectively on the training and subsequent experience of
      two operators in transseptal ablation of arrhythmias arising in the left atrium
      and left atrioventricular annulus, to show whether, with adequate training and
      careful attention to detail, this is a safe and effective technique. SETTING:
      Electrophysiological studies and transseptal procedures were performed in the
      electrophysiology laboratories of the Moffatt Hospital, University of California
      at San Francisco (39) and Manchester Royal Infirmary (65) from January 1993 to
      June 1997. Close supervision by a fully trained operator was provided for at
      least the first 20 procedures performed by each operator. PATIENTS: 94
      consecutive patients underwent electrophysiological study and ablation for Wolff
      Parkinson-White syndrome with left sided accessory connections (81 patients) or
      ectopic atrial tachycardia (13 patients); 104 transseptal procedures were done;
      eight patients required multiple procedures. RESULTS: 92 patients (98%) were
      initially successfully ablated. Five of 81 with accessory pathways (6%) and three
      of 13 with atrial tachycardia (23%) required further procedures. One patient with
      Wolff-Parkinson-White syndrome could not be ablated at a second procedure. Long
      term success rate for accessory pathway ablation was therefore 99%. Procedures
      were abandoned in three patients because of minor complications. All were
      subsequently ablated successfully by a transseptal approach on another day.
      CONCLUSIONS: The transseptal approach is safe and effective for ablation of left
      sided arrhythmias. The technique has similar success rates to the retrograde
      transaortic approach but without the risk of inadvertent damage to the coronary
      arteries or aortic valve.

PMID- 9616348
TI  - Ventricular pacemaker upgrade: experience, complications and recommendations.
AB  - OBJECTIVE: To assess outcomes of pacemaker upgrade from single chamber
      ventricular to dual chamber. DESIGN: Retrospective analysis of patients
      undergoing the procedure. SETTING: Specialist cardiothoracic unit. PATIENTS: 44
      patients (15 female, 29 male), mean (SD) age at upgrade 68.2 (12.9) years.
      INTERVENTIONS: Upgrade of single chamber ventricular to dual chamber pacemaker.
      MAIN OUTCOME MEASURES: Procedure duration and complications. RESULTS: Principal
      indications for upgrade were pacemaker syndrome (17), "opportunistic"--that is,
      at elective generator replacement (8), heart failure (7), non-specific
      breathlessness/fatigue (7), and neurally mediated syncope (3). Mean (SD) upgrade
      procedure duration (82.9 (32.6) minutes) significantly exceeded mean VVI
      implantation duration (42.9 (13.3) minutes) and mean DDD implantation duration
      (56.6 (22.7) minutes) (both p < 0.01). Complications included pneumothorax (1),
      ventricular arrhythmia requiring cardioversion (2), protracted procedure (10),
      atrial lead repositioning within six weeks (8), haematoma evacuation (1),
      superficial infection (1), and admission to hospital with chest pain (1); 20
      patients (45%) suffered one or more complications including four of the eight who
      underwent opportunistic upgrade. CONCLUSIONS: Pacemaker upgrade takes longer and
      has a higher complication rate than either single or dual chamber pacemaker
      implantation. This suggests that the procedure should be performed by an
      experienced operator, and should be undertaken only if a firm indication exists.
      Patients with atrial activity should not be offered single chamber ventricular
      systems in the belief that the unit can be upgraded later if necessary at minimal
      risk.

PMID- 9616349
TI  - Electrocardiographic and morphometric features in patients with ventricular
      tachycardia of right ventricular origin.
AB  - OBJECTIVE: To study differences between repetitive monomorphic ventricular
      tachycardia (RMVT) of right ventricular origin, and ventricular tachycardia in
      arrhythmogenic right ventricular dysplasia (ARVD). PATIENTS: Consecutive groups
      with RMVT (n = 15) or ARVD (n = 12), comparable for age and function. METHODS:
      Analysis of baseline, tachycardia, and signal averaged ECGs, clinical data, and
      right endomyocardial biopsies. Pathological findings were related to regional
      depolarisation (QRS width) and repolarisation (QT interval, QT dispersion).
      RESULTS: There was no difference in age, ejection fraction, QRS width in leads I,
      V1, and V6, and QT indices. During ventricular tachycardia, more patients with
      ARVD had a QS wave in V1 (p < 0.05). There were significant differences for
      unfiltered QRS, filtered QRS, low amplitude signal duration, and the root mean
      square voltage content. In the absence of bundle branch block, differences became
      non-significant for unfiltered and filtered QRS duration. Mean (SD) percentage of
      biopsy surface differed between RMVT and ARVD: normal myocytes (74(3.4)% v
      64.5(9.3)%; p < 0.05); fibrosis (3(1.7)% v 8.9(5.2)%; p < 0.05). When all
      patients were included, there were significant correlations between fibrosis and
      age (r = 0.6761), and fibrosis and QRS width (r = 0.5524 for lead I; r = 0.5254
      for lead V1; and r = 0.6017 for lead V6). CONCLUSIONS: The ECG during tachycardia
      and signal averaging are helpful in discriminating between ARVD and RMVT
      patients. There are differences in the proportions of normal myocytes and
      fibrosis. The QRS duration is correlated with the amount of fibrous tissue in
      patients with ventricular tachycardia of right ventricular origin.

PMID- 9616350
TI  - Nocturnal desaturation in patients with stable heart failure.
AB  - OBJECTIVE: To determine the prevalence of sleep disordered breathing within a
      United Kingdom heart failure population. SUBJECTS: 104 patients and 21 matched
      normal volunteers. METHODS: Overnight home pulse oximetry with simultaneous ECG
      recording in the patient group; daytime sleepiness was assessed using the Epworth
      sleepiness scale (ESS); 41 patients underwent polysomnography to assess the
      validity of oximetry as a screening test for Cheyne-Stokes respiration. RESULTS:
      Home oximetry was a good screening test for Cheyne-Stokes respiration
      (specificity 81%, sensitivity 87%). Patients with poorer New York Heart
      Association (NYHA) classes had higher sleepiness scores (p < 0.005). Twenty three
      patients had "abnormal" patterns of nocturnal desaturation suggestive of Cheyne
      Stokes respiration. The mean (SEM) frequency of dips in Sao2 exceeding 4% was
      10.3 (0.9) per hour in the patients and 4.8 (0.6) in normal controls (p < 0.005).
      Ejection fraction correlated negatively with dip frequency (r = -0.5, p < 0.005).
      The patient subgroup with > or = 15 dips/hour had a higher mean (SEM) NYHA class
      (3.0 (0.2) v 2.3 (0.1), p < 0.05), and experienced more ventricular ectopy (220
      (76) v 78 (21) beats/hour, p < 0.05). There was no excess of serious arrhythmia.
      CONCLUSIONS: Nocturnal desaturation is common in patients with treated heart
      failure. Low ejection fraction was related to dip frequency. Lack of correlation
      between dips and ESS suggests that arousal from sleep is more important than
      hypoxia in the aetiology of daytime sleepiness in heart failure. Overnight
      oximetry is a useful screening test for Cheyne-Stokes respiration in patients
      with known heart failure.

PMID- 9616351
TI  - Tyrosine phosphorylation of platelet derived growth factor beta receptors in
      coronary artery lesions: implications for vascular remodelling after directional
      coronary atherectomy and unstable angina pectoris.
AB  - BACKGROUND: Growth factors such as platelet derived growth factor (PDGF) have
      been postulated to be important mediators of neointimal proliferation observed in
      atherosclerotic plaques and restenotic lesions following coronary interventions.
      Binding of PDGF to its receptor results in intrinsic receptor tyrosine kinase
      activation and subsequent cellular migration, proliferation, and vascular
      contraction. AIMS: To investigate whether the concentration of PDGF beta receptor
      tyrosine phosphorylation obtained from directional coronary atherectomy (DCA)
      samples correlate with atherosclerotic plaque burden, the ability of diseased
      vessels to remodel, coronary risk factors, and clinical events. METHODS: DCA
      samples from 59 patients and 15 non-atherosclerotic left internal thoracic
      arteries (LITA) were analysed for PDGF beta receptor tyrosine phosphorylation
      content by receptor immunoprecipitation and antiphosphotyrosine western blot. The
      amount of PDGF beta receptor phosphorylation was analysed in relation to
      angiographic follow up data and clinical variables. RESULTS: PDGF beta receptor
      tyrosine phosphorylation in the 59 DCA samples was greater than in the 15 non
      atherosclerotic LITA (mean (SD) 0.84 (0.67) v 0.17 (0.08) over a control
      standard, p < 0.0001). As evaluated by stepwise regression analysis,
      incorporation of both PDGF beta receptor tyrosine phosphorylation and immediate
      gain correlated strongly (adjusted r2 = 0.579) with late loss, although PDGF beta
      receptor tyramine phosphorylation alone correlated poorly with late loss.
      Multivariate regression analysis of coronary risk factors and clinical events
      revealed unstable angina as the most significant correlate of PDGF beta receptor
      tyrosine phosphorylation (F value 20.009, p < 0.0001). CONCLUSIONS: PDGF beta
      receptor tyrosine phosphorylation in atherosclerotic lesions is increased
      compared with non-atherosclerotic arterial tissues. The association of PDGF beta
      receptor tyrosine phosphorylation with immediate gain strongly correlates with
      vascular remodelling. PDGF beta receptor tyrosine phosphorylation correlates with
      unstable angina pectoris.

PMID- 9616352
TI  - Relation of biophysical response of coarcted aortic segment to balloon dilatation
      with development of recoarctation following balloon angioplasty of native
      coarctation.
AB  - OBJECTIVE: To evaluate the role of biophysical response of the coarcted segment
      to balloon dilatation in the causation of aortic recoarctation. SETTING: Tertiary
      care centre/university hospital. DESIGN: Retrospective case series. METHODS:
      Records of 67 consecutive infants and children undergoing balloon angioplasty of
      native aortic coarctations were examined for an 8.7 year period ending September
      1993. At 12 months (median) follow up catheterisation, 15 (25%) of 59 children
      developed recoarctation, defined as a gradient > 20 mm Hg. Stretch (balloon
      circumference--preballoon coarcted segment circumference/preballoon coarcted
      segment circumference), gain (postballoon coarcted segment circumference-
      preballoon coarcted segment circumference), and recoil (balloon circumference-
      postballoon coarcted segment circumference) were calculated from measurements
      obtained from cineangiograms performed before and immediately after balloon
      dilatation. RESULTS: The stretch in 44 children without recoarctation (2.18
      (1.23)) was similar (p > 0.1) to that in 15 children with recoarctation (1.90
      (0.65)), implying that similar balloon dilating stretch was applied in both
      groups. Greater gain (p < 0.05) was observed in the group without recoarctation
      (8.8 (8.0) mm) than in the recoarctation group (5.7 (2.7) mm) but this was not
      substantiated in the infant population. However, the recoil was greater (p <
      0.001) in the group without recoarctation (5.1 (4.3) mm) than in the
      recoarctation group (2.1 (1.1) mm); this was also true in the infant group.
      CONCLUSIONS: Greater recoil in the patients without recoarctation implies
      preservation of intact elastic tissue in the coarcted segment. In the
      recoarctation group, with less recoil, the elastic properties may not have been
      preserved, thereby causing recoarctation. There might be a more severe degree of
      cystic medial necrosis in the recoarctation group than in the no recoarctation
      group. This needs confirmation in future studies.

PMID- 9616353
TI  - Radiofrequency catheter ablation for atrial flutter following orthotopic heart
      transplantation.
AB  - A 26 year old woman with a diagnosis of limb girdle muscular dystrophy and
      peripartum cardiomyopathy underwent orthotopic heart transplantation using
      standard atrial anastomoses. Recurrent atrial flutter was demonstrated in the
      absence of histological evidence of cellular rejection. Radiofrequency ablation
      of the flutter circuit was successfully performed allowing the avoidance of long
      term antiarrhythmic therapy. Ten weeks following ablation and cessation of
      amiodarone, presyncopal symptoms were found, associated with daytime and
      nocturnal sinus pauses of 2.9 seconds and 4.2 seconds, respectively. There was no
      evidence of AV node conduction impairment. In view of the continued absence of
      cellular rejection and the evident denervated state of the heart, the pauses
      reflected significant donor sinus node dysfunction; therefore, an AAIR permanent
      pacing system was implanted. At the time of pacemaker implantation atrial pacing
      at 150 beats/min did not produce significant PR interval prolongation or AV
      block. This case serves to advise rigorous follow up in such patients to continue
      to seek evidence of sinus node dysfunction potentially requiring permanent
      pacemaker implantation.

PMID- 9616355
TI  - Images in cardiology. Transoesophageal echocardiography diagnosis of a left
      coronary artery fistula draining into the right atrium.

PMID- 9616354
TI  - Radiofrequency ablation of a fascicular tachycardia after orthotopic cardiac
      transplantation.
AB  - A 51 year old male received an orthotopic transplant because of end stage
      ischaemic heart disease. The donor was a healthy male teenager with no history of
      arrhythmias or other cardiac conditions. The patient presented with
      haemodynamically stable tachycardia and dyspnoea five weeks post-transplant. The
      ECG showed a regular tachycardia of 140 beats/min with a right bundle branch
      block morphology, left axis deviation, and a QRS duration of 135 ms. There were
      independent P waves, capture, and fusion beats confirming the diagnosis of
      ventricular tachycardia. Endomyocardial biopsy showed moderate focal rejection
      that was thought to be responsible for the arrhythmia. During the following six
      months the patient had recurrent tachyarrhythmias; on each occasion the ECG
      morphology was the same and there was no cellular rejection. The patient
      continued to have frequent hospital admissions with ventricular tachycardia
      requiring DC cardioversion despite the empirical use of amiodarone, sotalol,
      disopyramide, and procainamide. Eighteen months after transplantation the
      diagnosis of fascicular tachycardia was suspected by ECG morphology and supported
      by successful termination with intravenous verapamil. The arrhythmia was
      successfully managed by radiofrequency ablation. This patient shows that
      arrhythmias following transplantation are not always related to rejection, and
      that other potentially reversible causes should be considered, particularly when
      the ECG during arrhythmia conforms to a classic configuration.

PMID- 9616356
TI  - Prevention of torsade de pointes in the congenital long QT syndrome: use of a
      pause prevention pacing algorithm.
AB  - Torsade de pointes in the congenital long QT syndrome (LQTS) is often pause
      dependent. Thus, the main goal of pacemaker treatment in the LQTS may be the
      prevention of pauses that facilitate the onset of torsade de pointes. A pause
      prevention pacing algorithm (rate smoothing) was used for arrhythmia prevention
      in a 14 year old girl with congenital LQTS. By temporarily increasing the pacing
      rate after spontaneous premature beats, rate smoothing down of 18% prevented
      postextrasystolic pauses, pause related T-U changes, and recurrence of pause
      induced torsade de pointes. Rate smoothing is a potentially useful tool that
      ought to be evaluated for the prevention of torsade de pointes in the LQTS.

PMID- 9616357
TI  - Rupture of a presumed hydatid cyst of the interventricular septum diagnosed by
      transoesophageal echocardiography.

PMID- 9616358
TI  - Possible association of a reduction in cardiovascular events with blood donation.

PMID- 9616359
TI  - Reduction in time delays in administering thrombolytic treatment.

PMID- 9616360
TI  - Serum cytokines and cardiovascular risk factors.

PMID- 9616362
TI  - Low antigen dose favours selection of somatic mutants with hallmarks of antibody
      affinity maturation.
AB  - The immunization schedule is critical for the derivation of high-affinity
      antibodies, low antigen dose being particularly favourable for the development of
      a more efficient memory response. To analyse the molecular events underpinning
      this preference, we analysed the early maturation of the response to the hapten 2
      phenyloxazolone (phOx) using low and high doses of immunogen. The phOx response
      is initially dominated by antibodies expressing the VkOx1-Jk5 light chain and the
      hallmark of the early stages of maturation is the substitution of His 34 by Asn
      or Gln increasing affinity 10- or eightfold, respectively, and of Tyr 36 by Phe.
      High-affinity antibodies express mutations at both sites. We cloned and sequenced
      VkOx1-Jk5 light chains from antigen-specific B cells taken 14 and 21 days after
      immunization with high and low antigen doses. We found that overall, the derived
      sequences were more mutated both at longer times and at higher dose. At day 14,
      His 34 was more frequently mutated at the higher than at the lower dose, while at
      day 21 the reverse was true. On the other hand, the His 34/Tyr 36 mutation pair
      was more frequent at low than high doses at both 14 and 21 days. Furthermore, at
      both times, the low immunization protocol yielded double mutants in cells with a
      lower mutation background. It appears therefore that while the higher dose may
      favour the acquisition of individual critical mutations, low-dose immunization
      favours the selection of a more focused mutational pattern, whereby advantageous
      mutations are associated with a low mutational background.

PMID- 9616361
TI  - Forms and functions of CD44.

PMID- 9616363
TI  - Human monoclonal antibodies specific to hepatitis B virus generated in a
      human/mouse radiation chimera: the Trimera system.
AB  - An approach to develop fully human monoclonal antibodies in a human/mouse
      radiation chimera, the Trimera system, is described. In this system, functional
      human lymphocytes are engrafted in normal strains of mice which are rendered
      immuno-incompetent by lethal total body irradiation followed by radioprotection
      with severe combined immunodeficient (SCID) mouse bone marrow. Following
      transplantation, human lymphocytes colonize murine lymphatic organs and secrete
      human immunoglobulins. We have established this system as a tool to develop fully
      human monoclonal antibodies, and applied it for the generation of monoclonal
      antibodies specific for hepatitis B virus surface antigen. A strong memory
      response to hepatitis B surface antigen was elicited in Trimera engrafted with
      lymphocytes from human donors positive for antibodies to hepatitis B surface
      antigen. The human specific antibody fraction in the Trimera was 10(2)-10(3)-fold
      higher as compared with that found in the donors. Spleens were harvested from
      Trimera mice showing high specific-antibody titres and cells were fused to a
      human-mouse heteromyeloma fusion partner. Several stable hybridoma clones were
      isolated and characterized. These hybridomas produce high-affinity, IgG, anti
      hepatitis B surface antigen antibodies demonstrating the potential of the Trimera
      system for generating fully human monoclonal antibodies. The biological function
      and the neutralizing activity of these antibodies are currently being tested.

PMID- 9616364
TI  - Immunoglobulin VH gene sequence analysis of spontaneous murine immunoglobulin
      secreting B-cell tumours with clinical features of human disease.
AB  - The 5T series of multiple myelomas (MM) and Waldenstrsom's macroglobulinaemia
      like lymphomas (WM), which developed spontaneously in ageing mice of the
      C57BL/KaLwRij strain, shows clinical and biological features that closely
      resemble their corresponding human diseases. In order to compare the patterns of
      somatic mutation in VH genes of mouse tumours with those of human counterparts,
      we have determined and analysed sequences of immunoglobulin VH genes in five
      cases of murine MM, two of WM and one of biclonal benign monoclonal gammopathy
      (BMG). Four of five MM and 2/2 WM cases used VH genes of the large J558 family;
      one MM used a gene of the VGAM3.8 family, and both clones of the BMG used genes
      of the 36-60 family. N-region insertions were observed in all cases, but D
      segment genes were only identified in 6/9 cases, which were all from the D-SP
      family and translated in reading frame 3. Compared with human MM, in which the VH
      genes have been found to be consistently hypermutated (mean% +/- SD = 8.8 +/-
      3.2), the degree of somatic mutation in the murine tumours was significantly
      lower (mean% +/- SD = 2.9 +/- 2.3). There was no significant evidence of
      clustering of replacement mutations in complementarity determining regions (CDR),
      a feature considered to be characteristic of antigen-selected sequences. However,
      one clone of the biclonal BMG case showed intraclonal variation, a feature
      described in some cases of human BMG. These results indicate that murine VH genes
      in mature tumours differ from human counterparts in the level and distribution of
      somatic mutations, but support the concept that BMG may be distinct from MM.

PMID- 9616365
TI  - Inherent properties of somatic hypermutation as revealed by human non-productive
      VH6 immunoglobulin rearrangements.
AB  - To study inherent properties of somatic hypermutation of human immunoglobulin
      genes in the absence of antigen selection, mutations of human non-productive VH6
      rearrangements enriched by subtractive hybridization were characterized. Ten
      unique clones arising from nine non-productive rearrangements were isolated. The
      frequency of mutation was 3.0%. Analysis of these mutations showed intrinsic bias
      for transitions and cytosine (C) to guanine (G) and G to C transversions. Bias
      for the strand of DNA targeted by mutation was not evident. Replacement mutations
      in the complementarity-determining region (CDR) occurred more frequently than
      expected based on the primary DNA sequence. This targeting of replacement
      mutations to the CDR may explain the conservation of the VH6 sequence in
      primates.

PMID- 9616366
TI  - The requirement of localized, CR2-mediated, alternative pathway activation of
      complement for covalent deposition of C3 fragments on normal B cells.
AB  - We have shown previously that normal B cells share, with Epstein-Barr virus
      transformed and malignant B cells, the ability to activate the alternative
      pathway (AP) of complement in vitro, resulting in the deposition of C3 fragments
      on the cell surface. Complement receptor type 2 (CR2, CD21) has been implicated
      directly as the site for formation of an AP convertase, which provides nascent
      C3b for deposition at secondary sites on the B-cell surface. In the present
      study, we have examined C3 fragment deposition in vitro in more detail by (1)
      assessing the importance of locally generated C3b for the deposition process, (2)
      investigating whether CR2 is the sole requirement for conferring AP activation
      capacity on a cell, and (3) determining whether CR2's function, as an AP
      activator, has different structural requirements from ligand binding. Increasing
      the availability of native C3, by increasing the serum (NHS) concentration,
      resulted in enhanced C3 fragment deposition on the B cells, whereas use of factor
      1-depleted NHS, which showed massive fluid phase C3 conversion during the
      incubation, diminished the deposition. Sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis (SDS-PAGE) and Western blotting of untreated and hydroxylamine
      treated lysates from B cells, after in vitro activation, revealed that the
      majority of C3 fragments (primarily iC3b and C3dg) had been covalently bound to
      the cell surface. Transfection of COS cells with wild-type CR2 or a deletion
      mutant lacking 11 of the molecule's 15 homologous domains, but retaining the
      ligand-binding site, revealed that expression of intact CR2 conferred a 12-fold
      increase in AP-activating capacity on these cells, while no increase in AP
      activity was apparent on cells transfected with the mutant CR2.

PMID- 9616367
TI  - Molecular heterogeneity in deficiency of complement protein C2 type I.
AB  - Deficiency of the complement protein C2 (C2D), one of the most common genetic
      deficiencies of the complement system, is associated with rheumatological
      disorders and increased susceptibility to infection. Two types of C2D have been
      recognized, each in the context of specific major histocompatibility complex
      (MHC) haplotypes; type I, a deletion, frameshift and premature stop codon
      resulting in absence of detectable C2 protein synthesis, and type II, missense
      mutations resulting in a block in secretion of C2 proteins. Analysis of C2
      expression in a child with C2 deficiency, a MHC haplotype different from those
      associated with type I or II C2D, and recurrent infections revealed additional
      molecular heterogeneity among C2 deficient patients. No detectable C2 protein was
      synthesized in the child's fibroblasts under conditions supporting C2 synthesis
      and secretion in normals and the child's C2 mRNA was reduced to 42% of normal.
      Nucleotide sequencing of RT-PCR fibroblast mRNA and genomic DNA revealed a type I
      C2 deficiency (28 base-pair deletion) on one allele and a previously unrecognized
      two base-pair deletion in exon 2 on the other. Expression of the closely linked
      factor B gene was markedly decreased (Bf mRNA 25% of normal), though Bf was up
      regulated appropriately by interferon-gamma and the flanking sequence containing
      the Bf promoter was normal in this C2-deficient patient. Moreover, the
      concentration of Bf protein was normal in the patient's plasma.

PMID- 9616368
TI  - Human HER-2/neu protein immunization circumvents tolerance to rat neu: a vaccine
      strategy for 'self' tumour antigens.
AB  - Many newly defined tumour antigens are 'self' proteins. Immunizing cancer
      patients against these antigens may be difficult due to tolerance. The HER-2/neu
      oncogenic protein is such a 'self' tumour antigen. Rat neu is homologous with
      human HER-2/neu and provides a model system for studying vaccination strategies.
      Rats are tolerant to rat neu. Vaccination with this 'self' protein elicits no
      detectable immune response. The current studies evaluated whether tolerance to
      rat neu can be circumvented by immunizing with the highly homologous foreign
      human HER-2/neu protein. Rats were immunized with human HER-2/neu intracellular
      domain (hICD) protein that is 92% homologous to rat neu ICD. Animals immunized
      with hICD developed significant antibody and T-cell responses that were specific
      for both human HER-2/neu and rat neu. Neu-specific antibodies were present in
      titres of greater than 1:200,000. Analysis of the specificity of the antibody
      response using synthetic peptides demonstrated substantial reactivity to an
      epitope with 100% homology between rat and human protein. Significant T-cell
      responses (stimulation index > 10) to hICD and rat neu protein (stimulation index
      > 4) were detected. The T cells also responded to both human and rat ICD. The
      results imply that immunization with foreign proteins, which are highly
      homologous to 'self' tumour antigens, may be an effective vaccine strategy for
      'self' tumour antigens.

PMID- 9616369
TI  - Tolerogenic activity of polyethylene glycol-conjugated lysozyme distinct from
      that of the native counterpart.
AB  - Conjugation of proteins with polyethylene glycol (PEG) has been reported to make
      the proteins tolerogenic. Native proteins are also potentially tolerogenic when
      given without adjuvants. We compared immunotolerogenic activities between PEG
      conjugated and native hen egg-white lysozyme (HEL). BALB/c mice were given
      consecutive weekly intraperitoneal administrations of PEG-conjugated HEL,
      unmodified HEL or phosphate-buffered saline (PBS), for 3 weeks, then challenged
      with HEL in Freund's complete adjuvant. The pretreatment with PEG-HEL tolerized
      both T-cell and humoral responses, while native HEL tolerized only the T-cell
      response. Immunoglobulin G1 (IgG1) antibody was already elevated in HEL
      pretreated mice prior to challenge immunization, followed by suppressed IgG2a and
      IgG2b, but spared IgG1 production after the antigen challenge, whereas PEG-HEL
      pretreated mice produced no antibody in all IgG subclasses prior and subsequent
      to the antigen-challenge. Production of interleukin-2 (IL-2) and interferon-gamma
      (IFN-gamma) by lymphoid cells in response to HEL in vitro was markedly suppressed
      in both the antigen-pretreated groups, while suppression of IL-4 production was
      evident only in PEG-HEL-, not in HEL-pretreated animals. Involvement of
      suppressor cells in these tolerance states was found to be unlikely, and the
      immunological property of PEG-HEL differed from deaggregated HEL that was similar
      to the original HEL. These results suggest a unique immunotolerogenic activity of
      PEG-conjugated proteins to suppress both T-helper type-1 (Th1)- and Th2-type
      responses, the result being extensive inhibition of all IgG subclass responses,
      while tolerance induction by unconjugated soluble proteins tends to be targeted
      on Th1-, but spares Th2-type responses.

PMID- 9616370
TI  - T-cell receptor V delta-J alpha rearrangements in human thymocytes: the role of V
      delta-J alpha rearrangements in T-cell receptor-delta gene deletion.
AB  - The differentiation mechanisms that force thymocytes into the T-cell receptor
      (TCR)-alpha beta or TCR-gamma delta lineage are poorly understood, but
      rearrangement processes in the TCR-alpha/delta locus are likely to play an
      important role. It is assumed that the TCR-delta gene is deleted prior to V alpha
      J alpha rearrangements by rearrangement of the so-called TCR-delta-deleting
      elements delta Rec and psi J alpha. However, the TCR-delta gene can also be
      deleted via V delta-J alpha rearrangements. We studied the different TCR-delta
      deleting rearrangements of V delta 1, delta Rec, V delta 2 and V delta 3 to J
      alpha gene segments in human thymocytes and peripheral blood using polymerase
      chain reaction analysis. The V delta 1 gene segment is the most upstream V delta
      gene segment tested and appears to rearrange to almost all J alpha gene segments.
      In contrast, the delta Rec and V delta 2 gene segments only rearrange to the 5'
      located J alpha gene segments, thereby preserving an extensive TCR-alpha
      combinatorial diversity, because most J alpha gene segments are kept available
      for subsequent V alpha-J alpha rearrangements. Based on our combined data we
      hypothesize that the different V delta gene segments and the delta Rec gene
      segment play different roles in T-cell development with regard to TCR-delta
      deletion.

PMID- 9616371
TI  - Distal V beta promoters transcribe novel T-cell receptor-beta transcripts in
      early development.
AB  - The transcriptional activation of germline T-cell receptor (TCR) and
      immunoglobulin (Ig) genes has been proposed to promote the rearrangement of these
      genes. Here we report the identification of distal TCR promoters (PDs), located
      upstream of the previously characterized promoters in the mouse V beta 5.1 and V
      beta 8.1 gene segments, that are active in germline TCR genes in fetal thymus and
      liver in vivo. We also identified an immature T-cell clone, SL12.4, that
      expresses both endogenous and transfected PDs in a regulated manner in vitro. We
      propose that the transcription of these distal promoters in germline TCR genes
      may be important for inducing TCR gene rearrangements during T-cell development.
      Northern blot, RNase protection and reverse transcription-polymerase chain
      reaction (RT-PCR) analyses demonstrated that PDs are also transcribed from fully
      rearranged TCR genes in adult thymus, lymph node, and spleen. Although the
      functional significance of this expression is not known, our sequence analysis of
      the 5' leader in PD-derived V beta 5.1 and V beta 8.1 transcripts revealed the
      presence of several open reading frames (ORFs) that may encode novel polypeptides
      or regulate the efficiency of TCR beta translation.

PMID- 9616373
TI  - CD8+ T cells inhibit immunoglobulin E synthesis in low responder SJL/J mice.
AB  - In an effort to examine the basis for low IgE responsiveness of SJL/J strain
      mice, we analysed the profiles of cytokines, such as interleukin-2 (IL-2), IL-4
      and interferon-gamma (IFN-gamma), in SJL/J and A.SW/SnJ mice following
      immunization. Splenocytes of ovalbumin (OVA)-immunized SJL/J mice, secreted
      significantly higher levels of IL-4 and lower levels of IFN-gamma than those of
      A.SW/SnJ mice. A time-course analysis of cytokine expression in in vitro cultures
      of spleen cells indicated that the levels of IL-4 and IL-2 remained persistently
      high throughout in the cultures of SJL/J splenocytes as opposed to those of
      A.SW/SnJ. Depletion of CD4+ T cells in vivo suppressed the production of IL-2, IL
      4 and IFN-gamma suggesting that CD4 T cells are the producers of most cytokines
      in both SJL/J and A.SW/SnJ mice. Depletion of CD8+ T cells in vivo not only
      induced productive epsilon transcript but also enhanced IgE production in SJL/J
      mice. Moreover, CD8 depletion in SJL/J mice led to decreased production of IFN
      gamma, resulting in a net decrease in the ratio of IFN-gamma to IL-4. A similar
      shift in the IFN-gamma/IL-4 ratio was found in splenocytes of SJL/J mice
      following irradiation, which is known to enhance IgE synthesis in these mice.
      Taken together, it is concluded that low IgE responsiveness in SJL/J mice is not
      due to a defect in IL-4 production per se. Increased IFN-gamma production by the
      CD8+ T cells inhibits class switch and suppresses IgE antibody production in
      SJL/J mice.

PMID- 9616372
TI  - Analysis of cytokine production and V beta T-cell receptor subsets in irradiated
      recipients receiving portal or peripheral venous reconstitution with allogeneic
      bone marrow cells, with or without additional anti-cytokine monoclonal
      antibodies.
AB  - Irradiated (800 rads) AKR mice received intravenous (i.v.) reconstitution with a
      mixture of B10.BR T-depleted bone marrow cells and spleen cells. Only in groups
      of mice treated additionally with i.v. cyclophosphamide (Cy; 150 mg/kg), 24 hr
      before transplantation, was long-term (> 60% at 50 days) survival seen. In mice
      receiving only irradiation all animals died by 30 days post-transplantation.
      Histological changes consistent with graft-versus-host disease (GVHD) were seen
      in the liver of reconstituted mice at 30 days, along with an organ-specific
      increase in V beta 3 T-cell receptor-positive (TCR+) cells. No such increase in V
      beta 3 TCR+ cells was seen in the spleen from the same mice. These data are
      consistent with a tissue antigen-driven expansion of V beta 3 TCR+ cells
      associated with GVHD in the liver in this model. When we analysed cytokine
      production in vitro from CD3+ cells restimulated with 'host' (AKR) antigen
      presenting cells (APC), we found a transition in cytokine production from
      preferential synthesis of type-1 cytokines [interleukin-2 (IL-2) and interferon
      gamma (IFN-gamma)] at early times (day 15) post-reconstitution to increased
      production of type-2 cytokines [IL-4, transforming growth factor-beta (TGF-beta)
      and IL-10] at later times (day 30) post-reconstitution in Cy-treated recipients.
      Animals not receiving Cy did not show this 'switch' in cytokine production at
      later time points. We have observed a similar polarization in cytokine
      production, along with increased graft survival, in recipients of vascularized
      and non-vascularized allografts after portal venous (p.v.), but not i.v.,
      pretransplant donor-specific immunization. We next studied AKR mice receiving 800
      rads and subsequently reconstituted with B10.BR stem cells via the p.v. route.
      Again these mice showed prolonged survival (> 50% at 50 days), with polarization
      to IL-4, IL-10 and TGF-beta on restimulation of CD3+ cells in vitro at 30 days
      post-transplant and increased V beta 3 TCR+ cells in the liver. Infusion of anti
      IL-12 monoclonal antibodies into irradiated mice receiving i.v. cell
      reconstitution produced a similar pattern of changes to those seen after p.v.
      reconstitution, while a combination of anti-IL-10 and anti-TGF-beta monoclonal
      antibodies reversed the changes seen after p.v. reconstitution. These data are
      consistent with an important role for differential cytokine production in the
      regulation of GVHD following allogeneic bone marrow transplantation.

PMID- 9616374
TI  - Proliferation of CD3+ B220- single-positive normal T cells was suppressed in B
      cell-deficient lpr mice.
AB  - It is known that lpr mice develop systemic lymphadenopathy and lupus
      erythematosus-like autoimmune disease that are associated with the accumulation
      of CD4- CD8- (double-negative; DN) CD3+ B220+ abnormal T cells as well as normal
      mature CD4+ or CD8+ single-positive (SP) CD3+ T cells. In order to clarify the
      role of B cells in the lymphoproliferation and autoimmunity of lpr mice, we
      created B-cell-deficient C57BL/6 (B6) lpr mice (B6lpr/lpr microMT/microMT) by
      crossing B6lpr/lpr mice with B6 microMT/microMT mice in which the B-cell
      development was arrested at pre-B stage owing to a targeted disruption of the
      immunoglobulin mu heavy-chain gene locus. In the B-cell-deficient B6-lpr mice,
      both lymphadenopathy and splenomegaly were markedly suppressed. Although the
      accumulation of both CD3+ B220- SP normal T cells and CD3+ B220+ DN abnormal T
      cells was inhibited in the B-cell-deficient lpr mice, the decrease in numbers of
      CD3+ B220- SP normal T cells occurred more strikingly than that of the CD3+ B220+
      DN abnormal T cells. Glomerulonephritis did not develop in the B-cell-deficient
      lpr mice over 40 weeks. The present results indicate that the B cells thus play a
      crucial role in the extensive proliferation of normal CD3+ B220- mature SP T
      cells rather than the accumulation of abnormal DN T cells.

PMID- 9616375
TI  - Intranasal immunization with polymer-grafted microparticles activates the nasal
      associated lymphoid tissue and draining lymph nodes.
AB  - Waldeyer's ring is located at the juncture of the respiratory and alimentary
      tracts, where it is bombarded by inhaled and ingested antigens. However,
      knowledge of its exact function or consequences of its removal is incomplete.
      Recently, the murine nasal-associated lymphoid tissue (NALT) has been reported to
      have functional similarities to Waldeyer's ring and, thus, might be a suitable
      model to examine the function of oronasopharyngeal lymphoid tissues. To explore
      the capability of NALT to incite local mucosal and systemic immunity, we
      immunized mice intranasally (i.n.) with 3-(triethoxysilyl)-propyl-terminated
      polydimethylsiloxane (TS-PDMS)-grafted microparticles (MP), an inoculant
      previously shown to induce robust systemic and mucosal humoral immunity following
      intragastric (i.g.) administration. We demonstrated that i.n. immunization with
      low doses of microentrapped, but not soluble, human serum albumin (HSA) evoked
      robust circulating IgG responses (P < 0.05). Additionally, NALT cells isolated
      from MP-treated mice proliferated in vitro when restimulated with HSA (P < 0.05),
      suggesting that i.n. immunization with HSA-containing MP incited specific
      immunity via NALT cell activation. Coinciding with these observations, after i.n.
      MP administration HSA-specific spot-forming cells (SFC) were observed in NALT,
      and later posterior cervical lymph nodes (pCLN) and spleen (SPL), suggesting that
      the observed MP-induced specific systemic antibody responses emanated from the
      NALT. We also showed that i.n. immunization with HSA-containing TS-PDMS-grafted
      MP stimulated interleukin-4 (IL-4)-secreting lymphocytes in the NALT. This
      cytokine microenvironment was probably responsible for driving the IgG1 sera
      response observed after i.n. MP administration, via the migration of NALT-derived
      IgG1-committed B cells. Interestingly, unlike i.g. MP administration, i.n.
      immunization with HSA-containing MP did not evoke detectable specific IgA in any
      lymphoid tissue examined, or in nasal secretions, probably reflecting differences
      between NALT and other mucosae-associated lymphoid tissues (MALT).

PMID- 9616376
TI  - Early cytokine responses during intestinal parasitic infections.
AB  - Infections with gastro-intestinal nematodes elicit immune and inflammatory
      responses mediated by cytokines released from T-helper type-2 (Th2) cells. In
      vitro assays of cells from the mesenteric lymph nodes (MLN) of experimentally
      infected rodents confirm that, after about 1 week, the dominant cytokine
      responses to mitogens and antigens are those associated with this Th-cell subset.
      Polarization of the Th response in this way implies an initial local cytokine
      environment that favours Th2 development. However, experimental infections with
      Trichinella spiralis and Nippostrongylus brasiliensis show that, within 2 days of
      worms reaching the intestine, MLN cells (MLNC) respond with a Th1 rather than a
      Th2 response [i.e. there is an increase in mRNA for the type 1 cytokine
      interferon-gamma (IFN-gamma), and mitogen-stimulated MLNC release IFN-gamma
      rather than interleukin-5 (IL-5)]. Antigen stimulation at this time does not
      elicit IFN-gamma release and the MLNC cannot adoptively transfer immunity. Within
      a few days the MLNC phenotype changes. There is a Th2 response (IL-5 release) to
      both mitogen and antigen stimulation and MLNC can adoptively transfer immunity.
      Early release of IFN-gamma is T-cell dependent, with CD4+ T cells playing the
      major role. The data are discussed in relation to factors regulating the mucosal
      response to invasion by parasites.

PMID- 9616377
TI  - Inflammatory reactions in placental blood of Plasmodium falciparum-infected women
      and high concentrations of soluble E-selectin and a circulating P. falciparum
      protein in the cord sera.
AB  - To better understand reasons for increased susceptibility to malaria in
      pregnancy; and the interrelationships between maternal malaria, local immune
      reactions and the development of the fetus, concentrations of soluble interleukin
      10 (IL-10), cytokine receptors, adhesion molecules, a Plasmodium falciparum
      protein, glutamate-rich protein (GLURP) and antibodies to P. falciparum rhoptry
      associated protein-1 were measured among 105 Gambian women and their neonates.
      Peripheral blood concentrations of IL-10, soluble cytokine receptors and soluble
      adhesion molecules were found to be different from those concentrations measured
      in the placenta. Markers of inflammatory reactions: IL-10, sIL-2R, sIL-4R, and
      soluble tumour necrosis factor receptor I (sTNF-RI) were found in high
      concentrations in the placenta, indicating that inflammatory reactions take place
      in the placenta which has been regarded as an immunoprivileged site.
      Concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble
      intracellular adhesion molecule-1 (sICAM-1), potential adhesion receptors for
      malaria parasites, were associated with an active P. falciparum infection in the
      placenta although the associations did not reach significance. P. falciparum
      exoantigen, GLURP, was detected in cord blood indicating transplacental passage
      of malarial antigens. Concentrations of E-selectin were higher in cord blood
      samples compared with peripheral blood samples. This appeared to be associated
      with development of cord endothelial cells and not with P. falciparum infection.

PMID- 9616378
TI  - Resistance ranking of some common inbred mouse strains to Mycobacterium
      tuberculosis and relationship to major histocompatibility complex haplotype and
      Nramp1 genotype.
AB  - Six common inbred strains of mice and their F1 hybrids were examined for
      resistance to infection with the H37Rv strain of Mycobacterium tuberculosis.
      According to survival times after inoculation of 10(5) CFU intravenously (i.v.),
      the mice could be classified as being either highly susceptible (CBA, DBA/2, C3H,
      129/SvJ) or highly resistant (BALB/c and C57BL/6). F1 hybrids of susceptible and
      resistant strains were resistant. Although an examination of a limited number of
      H-2 congenic strains showed that the H-2k haplotype could confer susceptibility
      on a resistant strain, it was evident that non-major histocompatibility complex
      (MHC) genes were much more important. Resistant strains all possessed the
      susceptibility allele of the anti-microbial resistance gene, Nramp1. Results
      obtained with selected strains infected with 10(2) CFU of M. tuberculosis by
      aerosol agreed with the results obtained with mice infected i.v. The size of the
      bacterial inoculum was important in distinguishing between resistant and
      susceptible strains, in that a 10(7) inoculum overcame the resistance advantage
      of one strain over another.

PMID- 9616379
TI  - Cytokine regulation on the synthesis of nitric oxide in vivo by chronically
      infected human polymorphonuclear leucocytes.
AB  - To determine if nitric oxide (NO) is produced by chronically infected human
      polymorphonuclear leucocytes (PMNs) in vivo, inflamed exudates (periapical
      exudates: PE) collected from periapical periodontitis patients were examined.
      Cell-free supernatants and cells were separated by centrifugation. Significant
      levels of nitrite concentrations were observed in the supernatants. The
      production of inducible NO synthase (iNOS) in highly purified PMNs derived from
      PEs was then immunocytochemically determined using rabbit anti-human iNOS
      antiserum. In vitro, human peripheral blood PMNs (PB-PMNs) isolated from patients
      were cultured with a combination of Esherichia coli-lipopolysaccharide (LPS),
      recombinant human interferon-gamma (rhIFN-gamma) and/or interleukin-1 beta (rhIL
      1 beta). The stimulated PB-PMNs showed steady-state levels of nitrite. The
      stimulation of LPS, rhIFN-gamma and rhIL-1 beta showed more NO induction than
      that of LPS with either IFN-gamma or IL-1 beta, suggesting the synergistic
      effects of cytokines. Cryostat sections of surgically removed periapical tissues
      were also immunohistochemically examined for iNOS, IFN-gamma and IL-1 beta. Two
      colour immunohistochemistry revealed the interaction of iNOS-producing PMNs and
      IFN-gamma- or IL-1 beta-producing mononuclear cells. On the basis of these data,
      we concluded that with the stimulation of inflammatory cytokines derived from
      mononuclear cells, PMNs can spontaneously produce NO at the site of chronic
      infection. The present studies are consistent with a hypothesis suggesting that
      PMNs could be regulated and delicately balanced to produce NO by mononuclear cell
      derived cytokines in vivo. NO-producing cells may play a pivotal role in chronic
      inflammation.

PMID- 9616380
TI  - High-affinity immunoglobulin E receptor (Fc epsilon RI)-bearing eosinophils, mast
      cells, macrophages and Langerhans' cells in allergen-induced late-phase cutaneous
      reactions in atopic subjects.
AB  - We have used in situ hybridization (ISH) and immunohistochemistry (IHC) to
      investigate the kinetics of the expression for Fc epsilon RI mRNA (alpha-, beta-
      and gamma-chains), the alpha-chain protein product, as well as the phenotype of
      the mRNA- or protein-positive cells in allergen-induced late-phase skin reactions
      in atopic subjects. Compared with diluent controls, there were significant
      increases in the total number of mRNA+ cells for the alpha-, beta- and gamma
      chains for Fc epsilon RI at all time-points (6, 24 and 48 hr) after allergen
      challenge (P < 0.01). By double IHC/ISH significant increases in alpha-, beta-
      and gamma-chain mRNA+ macrophages, eosinophils, mast cells and CD1a+ cells were
      also observed after allergen challenge (P < 0.05). The distribution of Fc epsilon
      RI subunit (alpha-, beta-, or gamma-chain) mRNA+ co-localization was CD68+
      macrophages (42-47%), EG2+ eosinophils (33-39%), tryptase+ mast cells (5-11%) and
      CD1a+ Langerhans' cells (2-4%). Using single IHC, significant increases in the
      total number of Fc epsilon RI protein+ cells (P < 0.01) were observed 24 and 48
      hr after allergen challenge. Double IHC showed that the distribution of Fc
      epsilon RI+ cells was tryptase+ mast cells (33%), CD68+ macrophages (36%), EG2+
      eosinophils (20%), CD1a+ Langerhans' cells (4%) and unidentified cells (7%), at
      the 24-hr allergen-challenged sites. These observations suggest that the
      cutaneous late-phase reaction in man is associated with up-regulation of Fc
      epsilon RI on eosinophils, macrophages, mast cells and Langerhans' cells.

PMID- 9616381
TI  - Comparative cytokine gene expression: regulation and release by human mast cells.
AB  - Since data on the ability of human mast cells to produce various cytokines are
      scanty, we examined the mRNA expression, its modulation and the resulting protein
      expression of a number of well-characterized cytokines, using semi-quantitative
      reverse transcription-polymerase chain reaction of cell extracts and enzyme
      linked immunosorbent assays for analysis of cell supernatants. One million
      cells/ml of the human mast cell line HMC-1 were stimulated with 25 ng/ml phorbol
      myristate acetate (PMA), 5 x 10(-7) M calcium ionophore A 23187 (ionophore) or
      both stimuli combined for various time periods. Constitutive expression in
      unstimulated cells was found for interleukin-1 beta (IL-1 beta) -3, -4, -8,
      tumour necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF
      beta). Maximal mRNA up-regulation was observed by 2-4 hr, with a second peak for
      TNF-alpha at 24 hr. After a 4-hr stimulation, IL-13 expression was detectable as
      well, whereas for IL-12, only the p35 but not the p40 chain was found, and IL-2, 
      5, -7 and interferon-gamma (IFN-gamma) were not expressed at all. Large
      quantities of IL-8, TNF-alpha, granulocyte-macrophage colony-stimulating factor
      (GM-CSF) and IL-3 were secreted time-dependently over a 72-hr period, with lower
      levels of IL-1 beta, -6, -10 and TGF-beta and no detectable IL-2, -4 and IFN
      gamma protein. When IL-6 and IL-8 expression was compared in more detail, IL-6
      mRNA was found to be up-regulated only with ionophore but not PMA, whereas both
      stimuli alone or combined increased IL-8 mRNA expression. Preincubation with
      cycloheximide inhibited IL-6 but not IL-8 transcription, and incubation of
      stimulated cells with actinomycin D stabilized IL-8 and also IL-6 mRNA. These
      data suggest a selective regulation of distinct cytokines in human mast cells at
      the transcriptional and post-transcriptional levels. Furthermore, the spectrum of
      cytokines produced by HMC-1 cells supports the well-recognized role of mast cells
      in immediate-type hypersensitivity reactions as well as their potential colony
      stimulating and tissue-remodelling abilities.

PMID- 9616383
TI  - Surgical treatment of isolated forearm non-union with segmental bone loss.
AB  - Twenty-four isolated radius and ulna non-unions with segmental bone loss were
      operated on. Nine non-unions were in the radius, 15 in the ulna. The surgical
      technique consisted of removal of the necrotic bone, filling of the bone defect
      with an intercalary bone graft and internal fixation with a cortical bone graft
      fixed opposite to a plate. The average length of bone defect after freshening of
      the bone ends was 3.6 cm (range 2-10.5 cm). The average length of follow-up was
      90 months. In 23 cases union was achieved. In three cases a postoperative
      infection developed. Resolution of the infection after surgical debridement was
      achieved in two of these patients, while recurrent infection caused failure of
      the treatment in the third patient. Statistical analysis revealed a shorter
      healing time (p = 0.031) in the ulna non-unions (12.5 +/- 3.0 weeks) compared
      with the radius non-unions (16.4 +/- 4.2 weeks). Functional results were classed
      as excellent in 10 patients, satisfactory in six, unsatisfactory in seven and
      failure in one.

PMID- 9616384
TI  - Massive hydronephrosis associated with traumatic rupture.
AB  - Twelve cases of traumatic rupture of a massive hydronephrosis are reported. The
      key points in the diagnosis are: injury around the loin, peritonitis, a fall of
      pH in the abdominal paracentesis fluid, a rise of blood urea nitrogen (BUN) and
      structural abnormality of the affected renal pelvis seen on ultrasonography. The
      treatment differed according to the disease causing the hydronephrosis before the
      injury. All patients were treated surgically with a satisfactory overall cure
      rate. Follow-up of 12 years has not revealed any significant sequelae.

PMID- 9616382
TI  - Signalling through NK1.1 triggers NK cells to die but induces NK T cells to
      produce interleukin-4.
AB  - In vivo inoculation of specific antibody is an accepted protocol for elimination
      of specific cell populations. Except for anti-CD3 and anti-CD4, it is not known
      if the depleted cells are eliminated by signalling through the target molecule or
      through a more non-specific mechanism. C57BL/6 mice were inoculated with anti
      natural killer (NK1.1) monoclonal antibody (mAb). Thereafter spleen cells were
      harvested, stained for both surface and intracellular markers, and analysed by
      flow cytometry. As early as 2 hr post inoculation, NK cells were signalled to
      become apoptotic while signalling through the NK1.1 molecule activated NK1.1+ T
      cell receptor (TCR)+ (NK T) cells to increase in number, and produce interleukin
      4 (IL-4). Anti NK1.1 mAb was less efficient at signalling apoptosis in NK cells
      when NK T-cell deficient [beta 2-microglobulin beta 2m-deficient] mice were used
      compared with wild type mice. Efficient apoptotic signalling was restored when
      beta 2m-deficient mice were reconstituted with NK T cells. NK-specific antibody
      best signals the apoptotic process in susceptible NK cells when resistant NK T
      cells are present, activated, and secrete IL-4.

PMID- 9616385
TI  - Keep the nail plate on with Histoacryl.
AB  - Sutures are commonly used to secure nail plates after nail-bed repair. Here we
      describe a technique to secure nail plates using an adhesive--Histoacryl blue (n
      butyl-2-cyanoacrylate). We report a series of 16 avulsed nail plates secured with
      Histoacryl after nail bed repair with a satisfactory end result.

PMID- 9616386
TI  - Plasma cytokines and endotoxin levels in patients with severe injury and their
      relationship with organ damage.
AB  - In 17 patients plasma TNF-alpha and IL-8 were assayed with enzyme-linked
      immunosorbent assay. IL-6 activity in plasma was determined by bioassay with IL-6
      dependent cell line 7TD1. The limulus amoebocyte lysate chromogenic test was used
      for plasma endotoxin assay. Plasma cytokine levels in injured patients were
      significantly increased. Plasma TNF-alpha was shown to be increased earlier,
      while an increase in plasma IL-6 and IL-8 levels occurred late, all of which were
      shown to be significantly positively correlated with ISS, cardiac and hepatic
      enzyme activities, and index of renal function. In addition, obvious endotoxaemia
      occurred at an early stage of injuries, which was respectively significantly
      correlated with ISS and plasma TNF-alpha, IL-6 and IL-8 levels. Severe injuries
      could induce increased successive release of TNF-alpha, IL-6 and IL-8, and
      obvious endotoxaemia. The post injury release of cytokines might be related to
      endotoxaemia, and may play an important role in the development of organ damage
      after injury.

PMID- 9616387
TI  - Diagnosis and management of zone III carotid injuries.
AB  - The management of patients with extracranial carotid injury at the base of the
      skull (zone III) is challenging due to inaccessibility, severity, and associated
      injuries. In an effort to formulate a systematic approach to the evaluation and
      management of zone III carotid injuries, the records of 13 consecutive patients
      with such injuries were reviewed: nine sustained penetrating injuries and four
      had blunt injuries. A total of 16 arteries were injured: internal carotid (11),
      external carotid (four), and vertebral (one). Neurological examinations revealed
      a central nervous system deficit in 1/9 with penetrating injuries and in 4/4 with
      blunt injuries. Angiography in patients with penetrating injuries revealed
      pseudoaneurysm (five), intimal flap (five), transection (two), and AV fistula
      (one). Angiograms of patients with blunt injuries demonstrated pseudoaneurysm
      (2), dissection (1), and intimal flap (1). Three patients underwent operative
      repair of internal carotid injuries and/or ligation of external carotid injuries.
      Four patients were managed with endovascular balloon occlusion. The remaining
      patients were observed with or without anticoagulation. Neurologically the
      patients remained normal or had improved on follow up with the exception of one
      patient with a persistent hemiparesis after a blunt injury who had been observed.
      The conclusions are: (1) angiography at presentation is indicated, in stable
      patients, to delineate the injury and guide definitive management; (2) blunt
      injuries should generally be managed with anticoagulation. In cases of large or
      expanding pseudoaneurysms or when anticoagulation fails, endovascular balloon
      occlusion is indicated; (3) partial thickness penetrating injuries can be
      observed, while full thickness lesions should be managed with balloon occlusion;
      (4) operative vascular reconstruction should be reserved for unstable patients,
      patients with active bleeding, and patients requiring surgical exploration for
      associated injuries.

PMID- 9616388
TI  - The early stages of the repair of adult human diaphyseal fractures.
AB  - Periosteum was obtained within 10 days of injury from the site of 17 adult tibial
      diaphyseal fractures during internal fixation. Osteogenic cells, non-osteogenic
      cells and vascular elements were identified in situ using a variety of
      techniques. In all cases, the periosteum was thickened with randomly distributed
      plaques of cartilage and bone. Cells covering newly formed bone trabeculae
      expressed osteocalcin. Lectin-binding revealed high vascularity. Few mast cells
      were observed. Macrophages and acid phosphatase positive cells, some
      multinucleate, were observed in abundance. These findings suggest that the repair
      of the adult human diaphyseal fracture is similar to that of experimental
      fractures in rapidity of onset, high vascularity and in bone and cartilage
      formation. They differ in the fact that chondrogenesis and osteogenesis appear to
      be simultaneous in human fractures but sequential in experimental fractures. The
      paucity of mast cells suggests that they probably play no significant role in the
      repair of the human fractures.

PMID- 9616389
TI  - The management of corneal abrasions in accident and emergency.
AB  - Recent debate over the use of eyepads and mydriatics for corneal abrasions in
      ophthalmology departments (Mindin et al., 1996, JAMA 1996; 27: 837) has prompted
      this review of the management of small corneal abrasions (< 60% of cornea) in a
      large teaching hospital accident and emergency (A&E) department. Ninety-nine
      patients were studied who presented to the Leicester Royal Infirmary A&E
      Department with a corneal abrasion; 49 were given an eye pad and 50 were not
      given an eye pad. All patients received chloramphenicol (1%) ointment. There was
      no significance difference between the two groups in terms of the duration of
      pain (p > 0.2). Four patients developed corneal infections (two wore an eyepad,
      two had no eye pad). There was only one patient who suffered a transient but
      significant reduction in visual acuity (6/9-6/18), following the use of an eye
      pad and subsequent diagnosis in eye casualty of a dendritic ulcer. It is
      concluded that accident and emergency treatment of small corneal abrasions is
      safe and effective if an eye pad is not given. Previous criticisms of A&E
      management of eye problems (Nayeen and Stansfield, Archs Emerg Med, 1992; 9: 257)
      are unfounded in this department.

PMID- 9616390
TI  - Late results of surgical repair in recent ruptures of the lateral ligament of the
      ankle.
AB  - Between 1979 and 1994, 75 patients underwent primary repair of a Grade III
      rupture of the lateral ligament of the ankle. The operation was indicated after
      the demonstration of ankle instability on stress X-rays by anterior displacement
      of the talus by more than 8 mm or/and a talar tilt of more than 10 degrees. The
      patients were either young or engaged in sports activities or physically
      demanding jobs. An end-to-end suture of the torn ligament was undertaken under
      general anaesthesia. A non-weight-bearing cast was used for the first 2 weeks,
      followed by a walking cast until 6 weeks postoperatively. Sixty-one patients were
      followed up for 1-15 years (mean 10.3 years). At follow-up all but one patient
      had returned to their pre-injury level of activity without complaint or
      restriction.

PMID- 9616391
TI  - The management of urinary tract injuries after gunshot wounds of the anterior and
      posterior abdomen.
AB  - Gunshot wounds of the urinary tract are seen with increasing frequency due to the
      widespread use of firearms. There is much controversy regarding the optimal
      preoperative diagnostic evaluation and intraoperative management of such
      injuries. Debate also arises as to the need for mandatory exploration or the
      safety of non-operative management for carefully selected patients. Seventy-nine
      prospective patients with injuries of the urinary tract after a truncal GSW were
      analyzed. The incidence of renal repair, nephrectomy, bladder repair and ureteral
      repair was 14, 21, 27 and 9 per cent, respectively. Five (6 per cent) patients
      were managed non-operatively and 16 (20 per cent) more underwent abdominal but
      not renal exploration. From 21 (26.5 per cent) cases with complications, only
      three (4 per cent) patients developed complications which were associated with
      the urinary tract injuries. Although the majority of patients with GSWs of the
      urinary tract will require abdominal exploration, invasion of Gerota's fascia may
      be spared in cases of stable renal haematomas. A high index of suspicion followed
      by adequate exploration is required to avoid missed ureteral injuries. Bladder
      perforations almost always require surgical repair.

PMID- 9616392
TI  - High rates of psychosocial complications after road traffic injuries.
AB  - A total of 134 people, aged between 25 and 60, were randomly selected from the
      Traffic Injury Register in Goteborg and interviewed 2 years after the accident.
      They were asked by telephone about their lives before and after the accident.
      There was a high rate of complications, even after some minor injuries. Half of
      the respondents still reported travel anxiety. Pain, fear and fatigue were also
      common. Sixteen per cent of those employed could not return to their ordinary
      jobs. Nearly one-third reported a reduction in leisure-time activities. Cervical
      spine 'distortion' was the only diagnosis associated with a high rate of
      complications. Married/cohabiting individuals developed complications more often
      than single people (p = 0.01). A risk factor for women--but not for men--was if
      they had children (p = 0.004). With respect to dealing with insurance, inadequate
      medical information and poor psychosocial support were other risk factors.
      Intervention programmes offering psychological and social support should be
      included in the care of traffic accident victims.

PMID- 9616393
TI  - An evaluation of the factors affecting neurological recovery following spinal
      cord injury.
AB  - We reviewed 71 consecutive spinal cord injuries to determine the factors
      influencing neurological recovery. Sixty-three (35 tetraplegics and 28
      paraplegics) were available for follow-up at a mean of 29.6 months. The American
      Spinal Injury Association (ASIA) scoring system was used on admission and at
      follow-up to determine change in neurological status. Treatment with
      corticosteroids or surgical intervention had no significant effect on outcome.
      Tetraplegics, both complete and incomplete, had a significantly better outcome
      than paraplegics (p < 0.02). Incomplete cord injury carried a better prognosis of
      motor recovery (p < 0.0001). Pattern of injury was an important determinant of
      recovery in the complete tetraplegia group. We conclude that many factors
      influence recovery following spinal cord injury and the effect of treatment may
      be difficult to demonstrate.

PMID- 9616394
TI  - A case of coccygodynia due to coccygeal fracture secondary to parturition.

PMID- 9616395
TI  - Flexor hallucis longus tendon interposition in a fracture of the medial tubercle
      of the posterior process of the talus.

PMID- 9616396
TI  - Blunt abdominal trauma secondary to misuse of standard cleaning equipment: a
      preventable occupational hazard.

PMID- 9616397
TI  - A new perspective on blow-out fracture of the orbit.

PMID- 9616398
TI  - Brown-Sequard syndrome due to traumatic brachial plexus root avulsion.

PMID- 9616399
TI  - Jeffery type 2 injuries of the radial neck in children.

PMID- 9616400
TI  - Ruptured Baker's cyst causing posterior compartment syndrome.

PMID- 9616401
TI  - Shear fracture-dislocation of the lumbar spine without paraplegia.

PMID- 9616402
TI  - Delayed sacral laminectomy for cauda equina in a child following fracture
      dislocation of sacrum.

PMID- 9616403
TI  - A universal hip spica pedestal.

PMID- 9616404
TI  - Manipulation of hip fracture in the below-knee amputee.

PMID- 9616405
TI  - Intramedullary interlocking nailing of humeral fractures.

PMID- 9616406
TI  - Socioeconomic differentials in mortality among men within Great Britain: time
      trends and contributory causes.
AB  - STUDY OBJECTIVE: To assess the size of mortality differentials in men by social
      class in Scotland as compared with England and Wales, and to analyse the time
      trends in these differentials. SUBJECTS: Men from England and Wales and Scotland
      around each census from 1951 to 1981. METHODS: Poisson regression analysis was
      used to calculate relative indices of inequality for disease specific and all
      cause mortality as a measure of mortality differentials between social classes.
      This measure is not dependent on the size of the social class groups, so it can
      be used to compare the magnitude of differentials over time periods during which
      the relative sizes of social class groups change. MAIN RESULTS: While overall
      death rates were higher in Scotland than in England and Wales around the 1951,
      1961, and 1971 censuses the relative indices of inequality indicated smaller
      mortality differences between social classes in Scotland. Inequality, as indexed
      by the relative index of inequality, increased over time in both Scotland and
      England and Wales, but to a greater degree in Scotland, resulting in greater
      social class mortality differentials for Scotland in 1981 (the relative index of
      inequality increased from 1.40 to 2.43 for England and Wales, and from 1.22 to
      2.57 for Scotland between 1951 and 1981). This greater increase in the magnitude
      of inequalities in all cause mortality in Scotland seemed to result from
      increasing social class differentials in cardiovascular disease, accidents and
      external causes, and "all other causes of death". Examining the trends in overall
      death rates, it seems that the greater increase in social class differences in
      Scotland occurred because of the greater decrease in death rates among the
      privileged social groups, in combination with a smaller decrease (or a greater
      increase) in the death rates in the lower social class groups. CONCLUSIONS: This
      study has shown that trends in mortality and in inequalities in mortality differ
      within Great Britain. Although death rates were higher in Scotland than in
      England and Wales, smaller mortality differentials by social class were found in
      Scotland over the period 1951 to 1971. By 1981, however, social class mortality
      differentials were greater in Scotland than in England and Wales. The greater
      increase in the social class differentials over time in Scotland, may have
      contributed to the worsening overall mortality profile in Scotland as compared
      with England and Wales that occurred between 1971 and 1981.

PMID- 9616407
TI  - Differences in self reported morbidity by educational level: a comparison of 11
      western European countries.
AB  - STUDY OBJECTIVE: To assess whether there are variations between 11 Western
      European countries with respect to the size of differences in self reported
      morbidity between people with high and low educational levels. DESIGN AND
      METHODS: National representative data on morbidity by educational level were
      obtained from health interview surveys, level of living surveys or other similar
      surveys carried out between 1985 and 1993. Four morbidity indicators were
      included and a considerable effort was made to maximise the comparability of
      these indicators. A standardised scheme of educational levels was applied to each
      survey. The study included men and women aged 25 to 69 years. The size of
      morbidity differences was measured by means of the regression based Relative
      Index of Inequality. MAIN RESULTS: The size of inequalities in health was found
      to vary between countries. In general, there was a tendency for inequalities to
      be relatively large in Sweden, Norway, and Denmark and to be relatively small in
      Spain, Switzerland, and West Germany. Intermediate positions were observed for
      Finland, Great Britain, France, and Italy. The position of the Netherlands
      strongly varied according to sex: relatively large inequalities were found for
      men whereas relatively small inequalities were found for women. The relative
      position of some countries, for example, West Germany, varied according to the
      morbidity indicator. CONCLUSIONS: Because of a number of unresolved problems with
      the precision and the international comparability of the data, the margins of
      uncertainty for the inequality estimates are somewhat wide. However, these
      problems are unlikely to explain the overall pattern. It is remarkable that
      health inequalities are not necessarily smaller in countries with more
      egalitarian policies such as the Netherlands and the Scandinavian countries.
      Possible explanations are discussed.

PMID- 9616408
TI  - Deprivation indicators as predictors of life events 1981-1992 based on the UK ONS
      Longitudinal Study.
AB  - STUDY OBJECTIVE: To investigate the association between the level of social
      deprivation in electoral wards and various life events. Life events include
      mortality, self reported long term illness, and for women: still-birth,
      underweight birth, birth while a teenager, and sole registered birth.
      Associations with area deprivation are tested before and after allowing for
      levels of personal deprivation. DESIGN: Prospective census follow up using the
      Office for National Statistics Longitudinal Study. SETTING: England and Wales.
      PARTICIPANTS: A random sample of more than 300,000 people enumerated at the 1981
      census, and aged 10 to 64 in 1981. Some analyses are necessarily restricted to
      certain age/sex groups. OUTCOME MEASURES: Several outcomes in the decade 1981
      1992 are investigated: risk of premature death (before age 70, all cause), risk
      of long term limiting illness in 1991, and risk of inauspicious fertility
      outcomes in women. MAIN RESULTS: Without adjusting for personal circumstances all
      outcomes, except risk of stillbirth, show a clear, significant, and approximately
      linear association with social deprivation of ward of residence in 1981.
      Associations are much stronger for outcomes where a greater "social" component
      can be constructed (teenage birth, sole registered birth) than for outcomes that
      are probably more physiologically determined (mortality, stillbirth, low birth
      weight). When adjustment is made for personal disadvantage the simple
      associations with local area deprivation are all attenuated, especially for those
      living in the more deprived areas. CONCLUSIONS: A variety of adverse or
      "inauspicious" life events show association with residence in more deprived
      areas. These are particularly strong for teenage birth and sole registered birth,
      but are also stronger for long term illness than mortality. These associations
      seem to be largely because residence in more deprived areas is associated with
      personal disadvantage, which is more damaging to life chances than area of
      residence. For some outcomes there is evidence that the personally disadvantaged
      fare less well if living in relatively advantaged areas, than if living in more
      homogenously deprived areas.

PMID- 9616409
TI  - Biological monitoring of lead exposure in high risk groups in Berat, Albania.
AB  - STUDY OBJECTIVE: To determine blood lead concentrations in children living in an
      area with a battery plant in Berat, Albania. Another aim was to determine blood
      lead concentrations in mothers and cord blood levels in neonates from Berat and
      compare them with values found in Tirana. DESIGN: Cross sectional survey with a
      10% random sample of children, and a 10% sample of mothers and newborn. SETTING:
      Hospitals, schools, and kinder-gartens in Berat and Tirana, Albania PARTICIPANTS:
      129 preschool children, 373 school children, 151 mothers and their newborn. MAIN
      RESULTS: The mean observed blood lead concentrations in 84 preschool children
      living less than 2 km from the battery plant was 43.4 micrograms/dl (SD 23.0) and
      significantly higher than in 45 preschool children (mean 15.0 micrograms/dl, SD
      3.5) living more than 2 km from the plant. Mean lead concentrations in 145 school
      children living close to the plant were 26.6 micrograms/dl (SD 14.4) compared
      with 16.0 micrograms/dl in 228 school children living at a greater distance. In
      67% of the preschool children and 41% of the school children lead levels exceeded
      the WHO borderline level of 20 micrograms/dl, and 98% of preschool children, and
      82% of school children had values greater than 10 micrograms/dl. Mean lead
      concentrations in cord blood of 151 newborn was 8.9 micrograms/dl (median 8.8,
      range 4.9-20.0 micrograms/dl), and 10.6 micrograms/dl in blood of their mothers
      (median 10.0, range 5.0-25.4 micrograms/dl). Mean lead concentrations in Tirana
      were 8.9 (newborn), and 7.0 micrograms/dl (mothers). CONCLUSIONS: Blood lead
      concentrations in children from Berat are comparatively high and abatement
      measures are needed.

PMID- 9616410
TI  - Blood thiamin status and determinants in the population of Seychelles (Indian
      Ocean).
AB  - STUDY OBJECTIVE: Micronutrient deficiencies have become rare in industrialised
      countries as availability of fresh food, supplementation, and fortification have
      improved but a less favourable situation may still prevail in many developing
      countries. Blood thiamin status and determinants were therefore investigated in
      the Seychelles in view of the high incidence of dilated cardiomyopathy and as the
      staple diet is polished rice that is deficient in thiamin. DESIGN: This was a
      cross sectional population study using an age and sex stratified random sample.
      SETTING: Seychelles Islands (Indian Ocean). PARTICIPANTS: A subsample of 206
      subjects aged 25-64 years from the population of Seychelles. MAIN OUTCOME
      MEASURES: Measurement of total thiamin concentration in whole blood using high
      performance liquid chromatography. Dietary variables measured using a face to
      face semi-quantitative food questionnaire. RESULTS: Mean (SD) whole blood thiamin
      concentration was 77.9 (22.4) nmol/l and low concentration (< 70 nmol/l) was
      found in 37% of the subjects (95% CI: 31%, 44%). Blood thiamin was significantly
      related to education and diet but not to age, sex, smoking, and body mass index.
      Blood thiamin was associated positively with meat, vegetable, salad, and tea
      intake and negatively with alcohol and fish intake. However, no combination of
      the examined variables could explain more than 15% of the observed variance in
      blood thiamin values. CONCLUSIONS: These data suggest that the distribution of
      blood thiamin in the sampled population is shifted to lower values compared with
      that generally accepted as normal in European populations. Further research
      should establish the significance of such lower values in this specific
      population to facilitate clinical and public health action as necessary.

PMID- 9616411
TI  - Do general practitioner hospitals reduce the utilisation of general hospital
      beds? Evidence from Finnmark county in north Norway.
AB  - STUDY OBJECTIVE: To assess whether populations with access to general
      practitioner hospitals (GP hospitals) utilise general hospitals less than
      populations without such access. DESIGN: Observational study comparing the total
      rates of admissions and of occupied bed days in general hospitals between
      populations with and without access to GP hospitals. Comparisons were also made
      separately for diagnoses commonly encountered in GP hospitals. SETTING: Two
      general hospitals serving the population of Finnmark county in north Norway.
      PATIENTS: 35,435 admissions based on five years' routine recordings from the two
      hospitals. MAIN RESULTS: The total rate of admission to general hospitals was
      lower in peripheral municipalities with a GP hospital than in central
      municipalities without this kind of institution, 26% and 28% lower for men and
      women respectively. The corresponding differences were 38% and 52%, when analysed
      for occupied bed days. The differences were most pronounced for patients with
      respiratory diseases, cardiac failure, and cancer who are primarily or
      intermediately treated or cared for in GP hospitals, and for patients with stroke
      and fractures, who are regularly transferred from general hospitals to GP
      hospitals for longer term follow up care. CONCLUSION: GP hospitals seem to reduce
      the utilisation of general hospitals with respect to admissions as well as
      occupied bed days.

PMID- 9616412
TI  - Measuring outpatient resource use and case mix in ophthalmology in north east
      England.
AB  - OBJECTIVES: To test the extent to which two existing ambulatory case mix measures
      (Ambulatory Visit Groups and Ambulatory Patient Groups) and other variables can
      explain resource use variations in ophthalmic outpatient visits. DESIGN: Three
      week prospective study of three consultant outpatient clinics. SETTING: One
      ophthalmic hospital (Sunderland Eye Infirmary, Sunderland, Tyne and Wear) and
      three outreach clinics (South Tyneside District Hospital, South Shields, Tyne and
      Wear; Dryburn Hospital, Durham, Co Durham; and Hartlepool General Hospital,
      Hartlepool, Cleveland). SUBJECTS: 325 patients who visited ophthalmic outpatient
      clinics. MAIN OUTCOME MEASURES: Mean consultation time and mean cost
      distributions by case mix group, analysed by analysis of variance. RESULTS:
      Ambulatory case mix measures can explain some of the variation in resource use
      for outpatient visits, but different measures differ in the extent to which they
      can do so. Clinicians' behaviour also accounts for a significant amount of such
      variation. Simpler measures of visit type, without diagnostic or procedure
      information, do not explain resource use variations. CONCLUSIONS: Existing
      measures perform reasonably well, but their data requirements may preclude their
      introduction in the National Health Service. Caution is required in advocating
      simpler measures, however. The influence of clinical practice on resource use
      variations is important; in this study, most differences between clinicians were
      not attributable to differences in case mix.

PMID- 9616413
TI  - Monitoring fetal and infant survival using regional birth notification data in
      north east London.
AB  - OBJECTIVE: To demonstrate the use of aggregated, locally collected birth
      notification data to examine trends in birth-weight specific survival for
      singleton and multiple births. DESIGN: Retrospective analysis of 171,527 notified
      births and subsequent infant survival data derived from computerised community
      child health records. Validation of data completeness and quality was undertaken
      by comparison with birth and death registration records for the same period.
      SETTING: Notifications of births in 1989-1991 to residents of the North Thames
      (East) Region (formerly North East Thames Regional Health Authority). OUTCOME
      MEASURES: Birthweight specific stillbirth, neonatal, and postneonatal death
      rates. RESULTS: There was close correspondence between the notification and
      registration data. For 96% of the registered deaths a birth notification record
      was identified and for the majority of these the death was already known to the
      Community Child Health Computer. Completeness of birth-weight data, particularly
      at the lower end of the range, was substantially better in birth notification
      data. Comparison with the most recent published national data relating to
      birthweight specific survival of very low birthweight singleton and multiple
      births suggests that the downward trend of mortality is continuing, at least in
      this Region. CONCLUSIONS: The use of routinely collected aggregated birth
      notification data provides a valuable adjunct to existing sources of information
      about perinatal and infant survival, as well as other information regarding
      process and outcome of maternity services. Such data are required for comparative
      audit and may be more complete than that obtained from registration or hospital
      generated data.

PMID- 9616414
TI  - Age differential mortality in Spain, 1900-1991.
AB  - STUDY OBJECTIVE: To analyse the interindividual inequalities in mortality in
      Spain through the 20th century using the Gini coefficient, widely used as an
      income concentration index. DESIGN: Age mortality data were obtained from
      official publications of vital statistics and age and sex compositions were
      obtained from population census. The Gini coefficient was estimated. It can take
      values between 0 and 1. Zero represents the situation in which all subjects die
      at the same age, whereas when all but one subject dies at 25 the index reaches a
      figure of 1. MAIN RESULTS: In both men and women there was a trend to decrease
      age differential mortality (from 0.26 to 0.16 for men and from 0.26 to 0.12 for
      women). Nevertheless, transitory increases were produced in 1918 (influenza
      epidemic), and in the period of the Civil War of Spain, showing a more important
      increase in the mortality of young people than that of the elderly. A new
      increase was observed through the second half of eighties; it resulted from an
      AIDS epidemic and motor vehicle injuries. CONCLUSION: Inequalities in mortality
      in Spain have decreased through the 20th century.

PMID- 9616415
TI  - Predicting postnatal mental disorder with a screening questionnaire: a
      prospective cohort study from Zimbabwe.
AB  - BACKGROUND: Postnatal mental disorders are common causes of morbidity but are
      rarely diagnosed or treated in busy primary care clinics in developing countries.
      OBJECTIVE: To determine whether a brief psychiatric screening questionnaire used
      in the 8th month of pregnancy can predict postnatal mental disorder. STUDY
      DESIGN: Prospective cohort study. SITE: A peri-urban settlement in Zimbabwe.
      POPULATION: 500 women in the 8th month of pregnancy identified by traditional
      birth attendants and primary care clinics. SAMPLE: "High risk" cohort consisted
      of all women who scored 8 or more on the Shona Symptom Questionnaire (SSQ), an
      indigenous psychiatric questionnaire (n = 95). Low risk cohort consisted of 105
      women randomly selected from the remainder of the sampling frame. OUTCOME
      MEASURE: Revised Clinical Interview Schedule at six to eight weeks postpartum;
      scores of 14 or more indicate psychiatric caseness. RESULTS: The prevalence of
      postnatal mental illness was 16%. Odds ratios (95% confidence intervals) for high
      risk women becoming cases in the postnatal period were 10.6, 4.8, 23.9, p <
      0.0001 after adjustment for age, marital status, and occupation. CONCLUSIONS: A
      brief method of detecting women at high risk of developing a postnatal mental
      disorder can be used with reasonable accuracy in the 8th month of pregnancy.
      Further research is needed to determine whether interventions applied to this
      high risk group can reduce their postnatal morbidity.

PMID- 9616416
TI  - Effect of mammographic breast density on breast cancer screening performance: a
      study in Nijmegen, The Netherlands.
AB  - STUDY OBJECTIVE: To study the implications of breast density on mammographic
      screening performance. DESIGN: Screening outcomes of women with dense breast
      patterns were compared with those of women with lucent breast patterns (dense >
      25% densities, lucent < or = 25% densities); the women were screened in different
      periods (before/after improvement of the mammographic technique in 1982).
      SETTING: Nijmegen, the Netherlands, 1977-1994. PARTICIPANTS: Between 1977 and
      1994, 73,525 repeat screenings were performed in 19,152 participants (aged 50-69
      years) in the Nijmegen breast cancer screening programme (repeat screenings were
      defined as mammographic examinations that were preceded by an examination in the
      previous screening round). Participants were screened biennially with
      mammography. There were 258 screen detected and 145 interval cancers. MAIN
      RESULTS: Before 1982 (rounds 2-4) the predictive value of a positive screening
      test (PV+) was lower in women with dense breasts than in those with lucent
      breasts (dense 29% v lucent 52%, p = 0.003). Also, the ratio of screen detected
      cancers to the total number of screen detected plus interval cancers (as a proxy
      for sensitivity) was lower in this group (based on a one year interval: dense 63%
      v lucent 92%, p = 0.001 and based on a two year interval: dense 41% v lucent 68%,
      p = 0.002). Moreover, the survival rate was less favourable for those with dense
      breasts (p = 0.07). In rounds 5-10, there were no important differences with
      respect to PV+ (dense 66% v lucent 62%, p = 0.57) or survival (p = 0.48).
      Moreover, sensitivity based on a one year interval was nearly as high in women
      with dense breasts as in those with lucent breasts (85% v 86%, p = 0.75).
      However, based on a two year interval sensitivity was lower (dense 59% v lucent
      72%, p = 0.04). CONCLUSIONS: In the early screening years (rounds 2-4) high
      breast density had an unfavourable effect on screening performance. Nowadays, the
      situation has improved with respect to PV+, survival and detecting tumours in
      dense breasts with a lead time of up to one year, but little improvement has
      occurred in the detection of tumours with a lead time greater than one year.

PMID- 9616417
TI  - Use of sequential case-control studies to investigate a community Salmonella
      outbreak in Wales.
AB  - STUDY OBJECTIVE: To establish the source of a community outbreak of Salmonella
      typhimurium definitive type 124. DESIGN: Two stage case-control study. SETTING:
      Three districts in south east Wales. SUBJECTS: Cases of salmonella food poisoning
      and community controls. MAIN RESULTS: An initial case-control study identified an
      association between illness and eating ham (odds ratio 4.50, 95% confidence
      intervals 1.10, 21.8) and also found a possible association between illness and
      food bought from delicatessen stores (odds ratio 5.03, 95% confidence intervals
      1.01, 32.3). However, only after a second stage case-control study was a single
      common ham producer identified as the source (odds ratio 25.0, 95% confidence
      intervals 2.33, 1155). CONCLUSION: Sequential case-control studies are an
      important and underused tool in the investigation of community outbreaks.

PMID- 9616418
TI  - Childhood leg length and adult mortality: follow up of the Carnegie (Boyd Orr)
      Survey of Diet and Health in Pre-war Britain.
AB  - OBJECTIVE: To investigate the relation between childhood height, its components-
      leg length and trunk length--and mortality in adulthood. DESIGN: Cohort study
      based on the Carnegie (Boyd Orr) Survey of diet and health in pre-war Britain,
      1937-9. SETTING: The 14 centres in England and Scotland that participated in the
      Carnegie Survey and where children were examined. Scottish centres: Aberdeen,
      Dundee, West Wemyss, Coaltown of Wemyss, Hopeman, Methlick, Tarves, Barthol
      Chapel. English Centres: Liverpool, York-shire, Barrow in Furness, Wisbech,
      Fulham, and Bethnal Green. SUBJECTS: 2990 boys and girls aged between 2 years and
      14 years 9 months when they were examined in 1937-9. These children were drawn
      from 1134 families who underwent a one week assessment of family diet and home
      circumstances. Of these, 2547 (85%) have been traced and flagged using the NHS
      Central Register. MAIN OUTCOME MEASURES: Age adjusted overall, coronary heart
      disease, and cancer mortality in men and women in relation to age and sex
      specific z scores for height, leg length, and trunk length. All analyses were
      adjusted for the possible confounding effects of childhood and adult
      socioeconomic circumstances and childhood diet. RESULTS: Leg length was the
      component of childhood height most strongly associated with socioeconomic and
      dietary exposures. There was no significant relation between childhood height and
      overall mortality. Height-mortality relations were observed in relation to both
      coronary heart disease (CHD) and cancer. Leg length was the component of height
      most strongly related to cause specific mortality. In men and women CHD mortality
      increased with decreasing childhood leg length. Men in the lowest leg length
      quintile had a relative risk (RR) of 2.5 (95% CI 1.0 to 6.2) compared to those
      with the longest legs (linear trend p = 0.14). Similarly, women in the lowest leg
      length quintile had a RR of 3.9 (95% CI 0.8 to 19.0; linear trend p < 0.01).
      Adjustment for childhood and adult socioeconomic circumstances had little effect
      on these trends. In men, but not women, those who as children had long legs
      experienced increased cancer mortality. The significant relations between
      anthropometry and both CHD and cancer mortality were restricted to those aged < 8
      years when measured. CONCLUSIONS: These findings suggest that adverse diet and
      living conditions in childhood, for which leg length seems to be a particularly
      sensitive indicator, are associated with increased risk of CHD in adulthood and
      possibly reduced cancer risk. It is likely that these influences operate after
      birth, during the first few years of life.

PMID- 9616419
TI  - Education and occupational social class: which is the more important indicator of
      mortality risk?
AB  - STUDY OBJECTIVES: In the UK, studies of socioeconomic differentials in mortality
      have generally relied upon occupational social class as the index of
      socioeconomic position, while in the US, measures based upon education have been
      widely used. These two measures have different characteristics; for example,
      social class can change throughout adult life, while education is unlikely to
      alter after early adulthood. Therefore different interpretations can be given to
      the mortality differentials that are seen. The objective of this analysis is to
      demonstrate the profile of mortality differentials, and the factors underlying
      these differentials, which are associated with the two socioeconomic measures.
      DESIGN: Prospective observational study. SETTING: 27 work places in the west of
      Scotland. PARTICIPANTS: 5749 men aged 35-64 who completed questionnaires and were
      examined between 1970 and 1973. FINDINGS: At baseline, similar gradients between
      socioeconomic position and blood pressure, height, lung function, and smoking
      behaviour were seen, regardless of whether the education or social class measure
      was used. Manual social class and early termination of full time education were
      associated with higher blood pressure, shorter height, poorer lung function, and
      a higher prevalence of smoking. Within education strata, the graded association
      between smoking and social class remains strong, whereas within social class
      groups the relation between education and smoking is attenuated. Over 21 years of
      follow up, 1639 of the men died. Mortality from all causes and from three broad
      cause of death groups (cardiovascular disease, malignant disease, and other
      causes) showed similar associations with social class and education. For all
      cause of death groups, men in manual social classes and men who terminated full
      time education at an early age had higher death rates. Cardiovascular disease was
      the cause of death group most strongly associated with education, while the non
      cardiovascular non-cancer category was the cause of death group most strongly
      associated with adulthood social class. The graded association between social
      class and all cause mortality remains strong and significant within education
      strata, whereas within social class strata the relation between education and
      mortality is less clear. CONCLUSIONS: As a single indicator of socioeconomic
      position occupational social class in adulthood is a better discriminator of
      socioeconomic differentials in mortality and smoking behaviour than is education.
      This argues against interpretations that see cultural--rather than material-
      resources as being the key determinants of socioeconomic differentials in health.
      The stronger association of education with death from cardiovascular causes than
      with other causes of death may reflect the function of education as an index of
      socioeconomic circumstances in early life, which appear to have a particular
      influence on the risk of cardiovascular disease.

PMID- 9616420
TI  - Food patterns, flour fortification, and intakes of calcium and vitamin D: a
      longitudinal study of Danish adults.
AB  - STUDY OBJECTIVE: Deficiencies in calcium and vitamin D intakes are involved in
      the aetiology of osteoporosis, and health authorities recommend that the
      population consume a diet providing sufficient calcium and vitamin D. However, in
      1987 the Danish Government withdrew a mandatory fortification of flour with
      calcium. This study examines intakes of calcium and vitamin D over time, in
      relation to food patterns, recommendations, and legislation. DESIGN: Food and
      nutrient intakes were measured by a short food frequency questionnaire (FFQ) and
      a thorough diet history interview, in 1987/88, and again six years later.
      SETTING: Copenhagen County, Denmark. PARTICIPANTS: 329 men and women, aged 35-65
      years at first examination in 1987/88. RESULTS: At both examinations the non
      enriched median intakes of calcium in men as well as women were above the
      recommended 600 mg/day. However, apparently the fortification of flour supplied
      up to 30% of the total calcium intake, and without the mandatory fortification,
      the percentage of adults with intakes below this recommendation increased from 6%
      to 22%. This group of subjects consumed cheese, milk, and oatmeal less often than
      those who had calcium intakes over 600 mg/day. During the study period the median
      intakes of vitamin D, which were well below the recommended 5 micrograms/day, did
      not change significantly. Associations between foods and vitamin D intakes were,
      in general, weak and insignificant, except for a positive association with fish
      intake. CONCLUSIONS: Data on calcium intakes suggest that the decision to stop
      the mandatory fortification of flour with calcium may have been premature. The
      short FFQ may be used for a rough classification of people in relation to their
      calcium intake, while this method seems insufficient for ranking vitamin D
      intakes.

PMID- 9616421
TI  - Socioeconomic status and stomach cancer incidence in men: results from The
      Netherlands Cohort Study.
AB  - STUDY OBJECTIVE: To study the association between socioeconomic status (SES) and
      stomach cancer incidence (cardia and non-cardia) and the role of lifestyle
      factors in explaining this association. DESIGN: Prospective cohort study on diet
      and cancer that started in 1986. Data were collected by means of a self
      administered questionnaire. SETTING: Population originating from 204
      municipalities in the Netherlands. PARTICIPANTS: 58,279 men aged 55-69 years.
      After 4.3 years of follow up, 162 incident stomach cancer cases were detected (49
      cardia and 113 non-cardia cases). MAIN RESULTS AND CONCLUSIONS: After adjustment
      for age, a lower overall stomach cancer risk was found for men with the highest
      attained level of education (RR highest/lowest level = 0.54, 95% CI 0.33, 0.89,
      trend, p = 0.02). This association became less strong after additional adjustment
      for smoking, intake of vitamin C, beta carotene, alcohol and coffee, family
      history of stomach cancer, and history of stomach disorders (RR = 0.61, 95% CI
      0.34, 1.07, trend, p = 0.11). No clear association was found between occupation
      based SES indicators and stomach cancer risk. Analyses per subsite of stomach
      cancer revealed that for people with the highest level of education the age
      adjusted rate ratio for cardia cancer changed from 0.37 (95% CI = 0.13, 1.00) to
      0.60 (95% CI = 0.19, 1.87) after additional adjustment for lifestyle variables,
      whereas the rate ratio for non-cardia cancer (RR = 0.59, 95% CI 0.33, 1.05) did
      not change after additional adjustment.

PMID- 9616422
TI  - Cocaine use among heroin users in Spain: the diffusion of crack and cocaine
      smoking. Spanish Group for the Study on the Route of Administration of Drugs.
AB  - STUDY OBJECTIVE: To describe the prevalence and patterns of use of crack and
      cocaine hydrochloride among heroin users in Spain. To explore if the expansion of
      heroin smoking is accompanied by a similar phenomenon for cocaine. DESIGN: Cross
      sectional study in 1995. Face to face interviews using a structured
      questionnaire. SETTING: Three cities with different prevalences of heroin use by
      smoking: high (Seville), intermediate (Madrid), and low (Barcelona).
      PARTICIPANTS: 909 heroin users, 452 in treatment and 457 out of treatment. MAIN
      RESULTS: Last month prevalence of crack use was 62.3% in Seville, 19.4% in
      Madrid, and 7.7% in Barcelona. Most users in Madrid (86.5%) and Barcelona (100%)
      generally prepared their own crack, usually with ammonia as alkali; in Seville
      most users (69.7%) bought preprocessed crack. The proportion of users who began
      taking cocaine (crack or cocaine hydrochloride) by smoking has increased
      progressively since the seventies, rising to 74.1% in Seville, 61.5% in Madrid,
      and 28% in Barcelona in 1992-1995, with the earliest increase in Seville. The
      factors associated with crack use were: residence in Seville (odds ratio (OR) =
      16.3), cocaine hydrochloride use mainly by smoking (OR = 5.0), by sniffing (OR =
      2.7) or by injecting (OR = 2.5), heroin use mainly by smoking (OR = 2.8) and
      weekly use of cannabis (OR = 1.9). CONCLUSIONS: In Spain smoking cocaine may be
      progressively diffusing from the south west to the north east, similar to what
      has happened with smoking heroin, but beginning later in time. The factors
      associated with smoking cocaine are basically ecological or cultural in nature
      (characteristics of the available drugs and the main route of heroin
      administration in each city).

PMID- 9616423
TI  - Vitamins, selenium, iron, and coronary heart disease risk in Indians, Malays, and
      Chinese in Singapore.
AB  - STUDY OBJECTIVE: To examine the hypothesis that the higher rates of coronary
      heart disease (CHD) in Indians (South Asians) compared with Malays and Chinese is
      partly because of differences in antioxidants (vitamins A, C, and E, and
      selenium) and pro-oxidants (iron). DESIGN: Cross sectional study of the general
      population. SETTING: Singapore. PARTICIPANTS: Random sample of 941 persons aged
      30 to 69 years. MAIN RESULTS: There were moderate correlations between vitamin A
      and vitamin E, and between these vitamins and selenium. Mean plasma vitamins A
      and E were similar by ethnic group. Vitamin A concentration for Indians were (men
      0.66 and women 0.51 mg/l), Malays (men 0.67 and women 0.54 mg/l), and Chinese
      (men 0.68 and women 0.52 mg/l). Vitamin E concentrations for Indians were (men
      12.9 and women 12.8 mg/l), Malays (men 13.6 and women 13.3 mg/l), and Chinese
      (men 12.6 and women 12.6 mg/l). In contrast, mean plasma vitamin C concentrations
      were lower in Indians (men 5.7 and women 6.9 mg/l) and Malays (men 5.1 and women
      6.4 mg/l) than Chinese (men 6.3 and women 8.4 mg/l). Mean serum selenium was
      lower in Indians (men 117 and women 115 micrograms/l) than Malays (men 122 and
      women 122 micrograms/l) and Chinese (men 126 and women 119 micrograms/l). Mean
      serum ferritin was much lower in Indians (men 132 and women 50 micrograms/l) than
      Malays (men 175 and women 85 micrograms/l) and Chinese (men 236 and women 92
      micrograms/l). MAIN CONCLUSIONS: Lower vitamin C and selenium in Indians,
      particularly in combination, could play a part in their increased risk of CHD.
      Vitamins A and E, and ferritin (iron) have no such role. Lower vitamin C in
      Indians and Malays is probably because of its destruction by more prolonged
      cooking. In Indians, lower selenium is probably because of a lower dietary intake
      and the much lower ferritin to a lower dietary intake of iron and its binding by
      phytates.

PMID- 9616424
TI  - John Henryism and blood pressure among Nigerian civil servants.
AB  - STUDY OBJECTIVE: Among urban Nigerian civil servants, higher socioeconomic status
      is related to increased blood pressure. In the United States, the relation
      between increased blood pressure and low socioeconomic status or low level of
      education has been found to be potentiated by high effort active coping (John
      Henryism) among African-Americans. Thus, the potentiating effect of high effort
      active coping as measured by the John Henryism Active Coping Scale, on
      socioeconomic status, as measured by job grade, was considered in relation to
      blood pressure in a Nigerian civil servant population. DESIGN: The influence of
      John Henryism on the association between educational level or socioeconomic
      status and increased blood pressure was examined during a comprehensive blood
      pressure survey. John Henryism refers to a strong behavioural predisposition to
      actively cope with psychosocial environmental stressors. SETTING: Benin City,
      Nigeria. PARTICIPANTS: Nigerian civil servant sample of 658 adults, aged 20 to 65
      years. MAIN RESULTS: Among those with high John Henryism scores of upper
      socioeconomic status, whether measured by education level or job grade, there was
      a trend toward higher systolic and diastolic blood pressures, adjusted for age
      and body mass index, in men and women, though not statistically significant.
      CONCLUSIONS: This trend is consistent with recent findings of increased blood
      pressure among women and African-Americans with high John Henryism and high
      status jobs.

PMID- 9616425
TI  - Relation between attempted suicide and suicide rates among young people in
      Europe.
AB  - STUDY OBJECTIVE: To determine if there are associations between rates of suicide
      and attempted suicide in 15-24 year olds in different countries in Europe.
      DESIGN: Attempted suicide rates were based on data collected in centres in Europe
      between 1989 and 1992 as part of the WHO/EURO Multicentre Study of Parasuicide.
      Comparison was made with both national suicide rates and local suicide rates for
      the areas in which the attempted suicide monitoring centres are based. SETTING:
      15 centres in 13 European countries. PATIENTS: Young people aged 15-24 years who
      had taken overdoses or deliberately injured themselves and been identified in
      health care facilities. MAIN RESULTS: There were positive correlations (Spearman
      rank order) between rates of attempted suicide and suicide rates in both sexes.
      The correlations only reached statistical significance for male subjects:
      regional suicide rates, r = 0.65, p < 0.02; national suicide rates, r = 0.55, p <
      0.02. CONCLUSIONS: Rates of attempted suicide and suicide in the young covary.
      The recent increase in attempted suicide rates in young male subjects in several
      European countries could herald a further increase in suicide rates.

PMID- 9616426
TI  - Detecting measurement confounding in epidemiological research: construct validity
      in scaling risk behaviours: based on a population sample in Minnesota, USA.
AB  - STUDY OBJECTIVE: The purpose of this study was to construct and validate a
      behavioral risk index scale to determine if the scaled variable could be used to
      study possible latent dimensions of risk behaviour. DESIGN: Data from the
      Minnesota Behavioral Risk Factor Surveillance System (BRFSS) were used to
      construct and validate a behavioral risk index using item response theory
      methods. PARTICIPANTS: A representative sample of 3303 Minnesota adults 18 years
      of age and older. RESULTS: Massive evidence was found against the construct
      validity of the index scale as a measure of risk behaviour. Seven commonly
      studied risk behaviours could not be scaled into a valid construct of health
      behaviour for either men or women. Tests of scalability, homogeneity, and item
      independence were rejected. In addition, item bias was found for all of the items
      in relation to important exogenous variables, especially age and education.
      CONCLUSIONS: The risk behaviours do not represent sufficiently similar types of
      phenomena to form an additive scale of health related risk taking. Not only do
      the practices fall on different, undefined dimensions of behavior, subgroup
      differences in risk taking would be hidden by data reductions summing the
      behavioral practices into additive scales. The findings indicate that the
      behaviors have quite distinct meanings that should be studied separately.

PMID- 9616427
TI  - Lifestyle and occupation.

PMID- 9616428
TI  - Mentholated cigarettes and non-lung smoking related cancers in California, USA.

PMID- 9616429
TI  - Anxiety and depression in patients with lung cancer before and after diagnosis:
      findings from a population in Glasgow, Scotland.

PMID- 9616430
TI  - Social inequalities and realisation of opportunistic screening mammographies in
      Barcelona (Spain).

PMID- 9616431
TI  - Evidence-based vaccinology: the work of the Cochrane Vaccines Field.

PMID- 9616432
TI  - Relation between induced abortion and breast cancer.

PMID- 9616433
TI  - Long-term effects of hyaluronan on experimental osteoarthritis in the rabbit
      knee.
AB  - OBJECTIVE: Long-term assessment of the effect of hyaluronan (HA) on the articular
      cartilage and synovium in an animal knee joint during the development of
      osteoarthritis (OA). DESIGN: Sixty mature New Zealand white rabbits underwent
      unilateral anterior cruciate ligament transection (ACLT) and were divided into
      two groups. Group 1 (SA) received intra-articular injections of 0.3 ml hyaluronan
      (HA) (i.e., ARTZ, MW: 8 x 10(5)) beginning 4 weeks after ACLT, once a week for 5
      weeks. Group 2 (SV) received injections of the vehicle (phosphate buffered
      saline) in the same fashion as with the SA group. The contralateral nonoperated
      knee served as control. All animals were killed 21 weeks after surgery and their
      knee joints evaluated by gross morphologic, histologic, histomorphometric and
      biochemical analyses. RESULTS: Gross morphological inspection indicated that the
      femoral condyles from the knees injected with vehicle suffered more severe
      cartilage damage than cartilage from the knees injected with HA. Furthermore, two
      out of three histomorphometric parameters measured in the HA-treated cartilage
      (i.e., cartilage thickness and cartilage area which were not statistically
      different than control) provided evidence showing a protective effect of HA on
      the femoral condyles following ACLT. Biochemical analysis showed articular
      cartilage remaining on the femoral condyles following ACLT to have similar
      characteristics to contralateral controls. However, DNA concentration in the
      synovium from the ACLT knees of the vehicle-treated animals was greater than
      contralateral control, while this parameter was not statistically different than
      contralateral control in the HA treated animals. CONCLUSIONS: These results
      demonstrate a protective effect of HA on preservation of the articulating surface
      of the femoral condyle following ACLT up to 21 weeks post-surgery.

PMID- 9616434
TI  - Age- and injury-dependent concentrations of transforming growth factor-beta 1 and
      proteoglycan fragments in rabbit knee joint fluid.
AB  - OBJECTIVE: The purpose of the study was to characterize maturation-related
      changes of TGF-beta 1 and proteoglycan fragment (PG) concentrations in joint
      fluid of healthy rabbit knees, and to investigate changes associated with
      osteochondral injury and spontaneous repair. METHODS: In 26 young (age range: 12
      15 weeks), 26 adolescent (18-25 weeks), and 26 adult (33-44 weeks) New Zealand
      white rabbits, TGF-beta 1 and PG concentrations were analyzed in joint fluid
      samples which were taken before, and at several time intervals (max. 1 year)
      after creation of a osteochondral defect in the knee medial femoral condyle. At
      death, the characteristics of the regenerated tissue in the defect and any signs
      of degeneration of adjacent cartilage were recorded and graded. RESULTS: In
      preoperative samples, TGF-beta 1 and PG concentrations decreased with maturation
      (P < 0.01), and were moderately correlated (r = 0.51, P < 0.001). Shortly after
      trauma, the concentrations of both substances were found increased, which was
      followed by a decrease up to 3 months, and then again an increase up to 1 year.
      However, meanwhile PG concentrations had similar magnitude irrespective of age,
      TGF-beta 1 concentrations never reached similarly high levels in adulthood as in
      infancy or adolescence. The cartilage adjacent to the defect had more signs for
      degeneration in younger rabbits, and also osteophytes were more common in young
      than adult animals. CONCLUSION: The similar pattern for TGF-beta 1 and PG
      concentrations during postnatal maturation may reflect the stimulatory effect of
      TGF-beta 1 on proteoglycan synthesis. The higher TGF-beta 1 concentrations in
      younger animals may be a reason for their better healing capacity, but also for
      their higher susceptibility to osteoarthritic change compared to adult animals.

PMID- 9616435
TI  - Effects of diacerhein on granuloma induced cartilage breakdown in the mouse.
AB  - OBJECTIVE: Diacerhein, an anti-osteoarthritic agent, was tested for its ability
      to suppress synthesis of proinflammatory cytokines in a model of granuloma
      induced cartilage breakdown. DESIGN: 50 TO mice received a subcutaneous implant
      of cotton-wrapped rat femoral head cartilage for a period of 2 weeks. Animals (N
      = 10/group) were dosed daily with either 6 mg/kg p.o. diclofenac or diacetylrhein
      at 5, 15 or 50 mg/kg p.o. in 0.1.ml 1% gum tragacanth which served as a control.
      Implanted cartilages were assayed for glycosaminoglycan (GAG) and hydroxyproline
      content. The surrounding granulomas were assayed for interleukin-1 alpha (IL-1
      alpha), tumour necrosis factor-alpha (TNF-alpha) and IL-6. Statistical analysis
      was by Mann-Whitney U test. RESULTS: Diclofenac had no significant effect on GAG
      or hydroxyproline content of implanted cartilage or on granuloma cytokine
      concentrations. Diacerhein protected implanted cartilages against hydroxyproline
      loss, implanted control cartilages contained 220 micrograms hydroxyproline
      compared with diacerhein at 5, 15 and 50 mg/kg which produced a 21, 16 and 59%
      decrease in hydroxyproline loss compared with non-implanted controls (P < 0.05,
      0.05 and 0.001) respectively. Diacerhein also protected against GAG loss at 5
      mg/kg and 50 mg/kg, control cartilages contained 134 micrograms GAG compared with
      diacerhein at 5 mg/kg and 50 mg/kg which produced a 24 and 38% decrease in GAG
      loss respectively (P < 0.05 for both). Diacerhein significantly reduced granuloma
      interleukin-1 alpha content at 5 mg/kg (control level of 2.4 micrograms/ml
      reduced by 58%; P < 0.05), reduced TNF-alpha at 5 mg/kg and 15 mg/kg (reduced by
      61%: P < 0.01 and 49%: P < 0.05 respectively; control level of 469 pg/ml) and
      reduced IL-6 at 15 mg/kg and 50 mg/kg (control level of 537 pg/ml reduced by 60
      and 51%, respectively; P < 0.01 for both). CONCLUSIONS: The mechanism of the
      chondroprotective effects of diacerhein is not understood but may be explained by
      a reduction in the concentrations of proinflammatory cytokines.

PMID- 9616436
TI  - Correlation between biochemical composition and magnetic resonance appearance of
      articular cartilage.
AB  - OBJECTIVE: The objective of this study was to find a correlation between magnetic
      resonance (MR) appearance and biochemical composition of the normal articular
      cartilage by comparing the laminar aspects with the distribution of the two
      principal matrix components: proteoglycans and collagen. DESIGN: T2-weighted MR
      microimages of porcine cartilage-bone plugs, excised from both the habitually
      loaded and habitually unloaded regions of the proximal end of the humerus, were
      obtained using a spin-echo sequence. Proteoglycans (PGs) were monitored by
      histology and by measuring the uronate and the sulfur content of the tissue; a
      histologic method and the chemical determination of hydroxyproline were used for
      the evaluation of the collagen content. RESULTS: The 'loaded' cartilage exhibited
      the expected MR laminar appearance whereas the 'unloaded' tissue appeared to be
      more homogeneous. The PG content in the 'loaded' cartilage, was found to be 2.4
      times higher than in the habitually unloaded tissue, exhibiting an increasing
      trend from the articular surface to the bone. In the 'unloaded' cartilage the
      uronate distribution was more uniform with a higher concentration in the
      intermediate zone. The mean collagen content of both cartilage regions was found
      to be about 39% of the tissue dry weight. Histology and hydroxyproline
      distribution pattern showed that collagen was particularly concentrated at the
      surface and in a central zone of the 'loaded' cartilage whereas in the 'unloaded'
      tissue collagen was evident only at the surface. In accordance with the collagen
      distribution, transverse relaxation (T2) times in 'loaded' cartilage showed a
      minimum value at the articular surface and another minimum in a central region.
      On the contrary, the average T2 value of the 'unloaded' tissue was high at the
      surface and decreased rapidly in the deeper zones. CONCLUSION: These results
      demonstrate that the MR appearance of articular cartilage correlates with the
      collagen content, but not with that of PGs, of the different zones. Other matrix
      components might, however, influence the MR appearance by contributing to the
      macromolecular organization of the tissue.

PMID- 9616437
TI  - Bone scan and serum markers of bone and cartilage in patients with knee pain and
      osteoarthritis.
AB  - OBJECTIVE: To study the relations between knee joint abnormalities, reflected by
      bone scintigraphy and serum concentrations of cartilage oligomeric matrix protein
      (COMP) and bone sialoprotein (BSP). DESIGN: In a group of 38 individuals aged 37
      54 years with chronic knee pain for more than four years, both knees were
      investigated with bone scan. The bone scans were graded for the extent of
      abnormalities. Radiographs of both knees were graded for tibiofemoral and
      patellofemoral osteoarthritis (OA). Serum levels of COMP and BSP were measured by
      immunoassays. RESULTS: Bone scan abnormalities were detected in 26/38 individuals
      and radiographic OA in 23/38 individuals. The serum concentrations of COMP and
      BSP were significantly higher in the individuals with bone scan abnormalities (P
      = 0.02 and P = 0.004, respectively). In addition, the serum levels of COMP
      correlated positively with the extent of bone scan abnormalities (N = 38), r =
      0.56, P = 0.002. Serum BSP did not correlate to the extent of scan abnormalities.
      CONCLUSIONS: In individuals with knee pain, serum levels of COMP and BSP differ
      between those with or without bone scan abnormalities in the knee joints. This
      suggests that measurements of the serum levels of these markers have potential as
      means for evaluation of tissue changes in individuals with long standing knee
      pain in relation to early stages of OA.

PMID- 9616439
TI  - Transplantation of allograft chondrocytes embedded in agarose gel into cartilage
      defects of rabbits.
AB  - OBJECTIVE: Durable healing of full-thickness articular cartilage defects has been
      considered for a long time as a highly desirable, but unlikely event to occur. In
      recent years, conflicting reports on the outcome of in vitro and in vivo studies
      on chondrocyte and cartilage grafting into animal and human joints have raised
      new arguments for and against controlled repair of articular cartilage following
      injury. Some of the problems result from insufficient characterization of implant
      and repair tissue, and from too short follow up phases. Here we describe a new
      approach to repair articular cartilage defects in rabbit knees by allografting
      chondrocytes cultured in agarose gels. DESIGN: The implants were monitored over 6
      18 months and graded histologically, immunohistochemically, and electron
      microscopically, using a grading scale based on seven evaluation criteria.
      Control implants of pure agarose produced poor fibrous substitute tissue,
      insufficient healing and incomplete filling of the cartilage defects. After
      transplantation of allogenic chondrocytes embedded in agarose, the quality of the
      newly formed repair cartilage was superior with respect to type II collagen and
      proteoglycan content and cellular architecture when compared with untreated
      defects. Superficial fibrillation and degradation were significantly diminished
      or prevented. RESULTS: New subchondral bone formed at the level of the previous
      subchondral bone. In most cases the repair tissue merged with the host articular
      cartilage; normal calcified cartilage was the only tissue zone that did not
      participate in the integration of the transplant. By gross evaluation 24% of
      grafts showed an extent of recovery never observed in controls. The best results
      were obtained after 18 months when 47% of the grafts (N = 15) developed a
      morphologically stable hyaline cartilage. CONCLUSION: These studies demonstrate
      that agarose-embedded chondrocyte may prove a valuable tool for controlled repair
      of articular cartilage defects.

PMID- 9616438
TI  - Effect of IL-13 on cytokines, cytokine receptors and inhibitors on human
      osteoarthritis synovium and synovial fibroblasts.
AB  - OBJECTIVE: In this study we investigated the effect of interleukin-13 (IL-13), an
      anti-inflammatory cytokine, for potential therapeutic use in osteoarthritis (OA).
      DESIGN: We examined the effect of IL-13 on the synthesis and expression of
      interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), IL-1
      receptor antagonist (IL-1Ra) and stromelysin-1 on human OA synovial membrane in
      ex vivo cultures. In addition, we explored the effect of IL-13 on both the IL-1
      receptor (IL-1R) and TNF-receptor (TNF-R) systems on OA synovial fibroblasts.
      This included determination of the levels of IL-1 beta and TNF-alpha receptor
      binding, IL-1Ra and TNF-soluble receptors 55 and 75 (TNF-sR55 and TNF-sR75).
      RESULTS: In OA synovial membrane treated with LPS, IL-13 inhibited the synthesis
      of IL-1 beta, TNF-alpha and stromelysin-1, but increased IL-1Ra production. In
      addition, IL-13 reduced the level of IL-1 beta mRNA and stimulated the level of
      IL-1Ra mRNA. In synovial fibroblasts, IL-13 decreased the level of IL-1 binding,
      an effect related to the increased production of IL-1Ra. Although IL-13 had no
      effect on the TNF-R level, this cytokine markedly decreased the shedding of TNF
      R75. CONCLUSION: These experiments suggest that IL-13 is potentially useful in
      the therapeutic treatment of OA, as it could regulate the major pathological
      process of this disease by reducing the production of proinflammatory cytokines
      and metalloproteases, and favoring the production of IL-1Ra.

PMID- 9616440
TI  - Differences in the repair process of longitudinal and transverse injuries of
      cartilage in the rat knee.
AB  - OBJECTIVE: To clarify the relationship between type or direction of cartilage
      injury and its repair process, we investigated defects produced in rat knees
      histologically, immunohistochemically, and histomorphometrically. METHODS: A full
      thickness cartilage injury (1 mm wide and 5 mm long) was produced on the patellar
      groove of one knee (L-injury) and transversely on the other knee (T-injury) in 42
      male Wistar rats. Six rats each were sacrificed at 1, 2, 3, 4, 6 and 8 weeks
      after surgery, and cartilage tissues were obtained, prepared into 4 microns-thick
      histologic specimens, and stained with hematoxylin and eosin. Cartilage
      thickness, cartilage area, and surface roughness were measured using a computer
      system. Localization of S-100 proteins was evaluated with immunohistochemistry.
      RESULTS: Grossly, there were no difference in repair process between L- and T
      injuries. However, histological and histomorphometric differences became apparent
      after the third week: cartilage thickness, repair area, and surface roughness
      showed better recovery in L-injury than in T-injury. Appearance of S-100-positive
      protein preceded the appearance of chondrocytes, and L-injury presented S-100 in
      the entire defect while S-100 in T-injury appeared mainly on the margins of the
      defect. CONCLUSIONS: Repair mechanisms of cartilage injury differs according to
      injury direction. Better repair can be obtained in the injury which is parallel
      to the direction of joint motion.

PMID- 9616441
TI  - Accreditation of specialist palliative care: minimum standards or improved care?

PMID- 9616444
TI  - An evaluation of palliative care services for cancer patients in the Southern
      Health and Social Services Board of Northern Ireland.
AB  - An interview study of 55 lay carers of people who died from cancer in the
      Southern Board of Northern Ireland was undertaken using a combination of closed
      format and open-ended questions. The aim of the study was to evaluate palliative
      care services delivered in the last six months of their lives to cancer patients
      who died either at home or in hospital. Two-thirds of the deaths (36) occurred in
      the domestic home, 45 of the deceased were admitted as hospital inpatients, and
      the great majority were in receipt of community nursing (53) and general
      practitioner (54) services. Open-ended questions were used to allow respondents
      to give their views about services in some detail and their views about good and
      bad aspects of services were sought. While they were generally satisfied with
      services specific areas of difficulty were identified in each aspect of care
      addressed by the study. The most favourable assessments were made of community
      nursing with the greatest number of negative comments being made about inpatient
      hospital care. Differing interests between some of those who were dying and their
      lay carers were found in two areas: the receipt of help from nonfamily members
      and the information that the deceased received about their terminal status.

PMID- 9616443
TI  - The use of the Edmonton Symptom Assessment Scale (ESAS) within a palliative care
      unit in the UK.
AB  - The Edmonton Symptom Assessment scale (ESAS) was used on 1004 occasions to assess
      71 patients with advanced malignant disease admitted to a palliative care unit in
      the UK over a six-week period. The median length of inpatient stay was eight days
      (range 1-36) and the median survival from start of ESAS to death was 16 days
      (range 2-202). Across all patients there was a trend towards worsening symptom
      scores over the first five days from admission with a significant deterioration
      in appetite scores. When scores were analysed retrospectively over five days
      according to outcome (death--group 1, or discharge--group 2) there was a
      significant improvement in pain scores in group 2 but no change in overall score,
      and a significant deterioration in activity, drowsiness and appetite in group 1
      with no change in overall score. ESAS did not seem an appropriate tool in this
      group of patients as the total symptom scores were so often biased by the
      inevitable increase in individual symptom scores immediately prior to death.

PMID- 9616445
TI  - Development of an instrument to measure terminal restlessness.
AB  - Terminal restlessness is a clinical phenomenon that is frequently observed but
      poorly defined. Its management is important in providing good quality palliative
      care. We present the development of an objective observer-rated instrument to
      measure terminal restlessness.

PMID- 9616446
TI  - A comparison of artificial saliva and pilocarpine in the management of xerostomia
      in patients with advanced cancer.
AB  - This was a crossover study comparing a mucin-based artificial saliva (Saliva
      Orthana) and pilocarpine hydrochloride (Salagen) in the management of xerostomia
      in patients with advanced cancer. The pilocarpine was found to be more effective
      than the artificial saliva in terms of mean change in visual analogue scale
      scores for xerostomia (P = 0.003). Furthermore, more patients reported that it
      had helped their xerostomia, and more patients wanted to continue with it after
      the study. However, the pilocarpine was found to be associated with more side
      effects than the artificial saliva (P < 0.001). These side-effects were usually
      reported as being mild. Of the patients who used both treatments, 50% preferred
      the artificial saliva, and 50% preferred the pilocarpine. The commonest reason
      for preferring the artificial saliva was the fact that it was a spray, rather
      than a tablet.

PMID- 9616447
TI  - Opioid medication in the palliative care of motor neurone disease.
AB  - In the palliative care of patients with motor neurone disease (MND) symptoms are
      encountered that can be helped by the use of strong opioid medication. A
      retrospective survey of the 32 patients dying of MND at the Wisdom Hospice who
      required opioids showed that 75% received oral opioids, 94% received parenteral
      opioids and 72% received both oral and parenteral opioids. The median oral
      morphine dose was 60 mg/24 h, with a median duration of 51 days and the median
      parenteral dose was 180 mg/24 h with a median duration of use of three days. The
      results show that strong opioids can be used safely and effectively in the
      palliative care of patients with MND.

PMID- 9616448
TI  - Accuracy of prediction of survival by different professional groups in a hospice.

PMID- 9616449
TI  - Intrathecal baclofen and homeopathy for the treatment of painful muscle spasms
      associated with malignant spinal cord compression.
AB  - In this case study we describe a dual approach to the palliation of difficult
      muscle spasms using intrathecal baclofen via a fully implanted system, together
      with the homeopathic approach to symptom control. The homeopathy is seen to
      complement rather than to replace conventional prescribing and using both
      approaches together appears to have avoided the necessity for increasing drug
      doses and to have minimized side-effects. As well as encouraging us to take on
      experience from other disciplines, this case study also suggests that palliative
      care could be a forum for evaluating the effectiveness of the homeopathic
      approach in symptom control in carefully designed studies.

PMID- 9616450
TI  - Nonverbal communication and the use of art in the care of the dying.

PMID- 9616451
TI  - Phenomenological approaches to palliative care research.

PMID- 9616453
TI  - Evidence-based care at the end of life.

PMID- 9616452
TI  - The place of death of cancer patients in Antwerp.

PMID- 9616454
TI  - New directions in bereavement research: exploration of gender differences.
AB  - Psychological research on the phenomena of bereavement has moved from a concern
      to establish the range and severity of mental and physical health consequences,
      to the examination of factors that make particular persons or subgroups
      especially vulnerable, to most recently an investigation of ways of coping with
      loss that may influence the course of recovery and adjustment. This trend is
      illustrated by exploring gender differences in reactions to spousal bereavement.
      Both males and females are vulnerable to ailments and illnesses on becoming
      bereaved, but research has shown that widowers have even more excessive
      detrimental consequences than widows. A new framework that has been developed to
      help understanding of such processes in coping with loss is outlined.

PMID- 9616455
TI  - Nurse-patient communication in palliative care: an evaluation of a communication
      skills programme.
AB  - Good communication between nurses and patients is a central aspect of palliative
      care. However, evaluation of courses designed to improve nurses' communication
      skills has been inconclusive. Most courses have concentrated on skills training,
      although communication training programmes which have been integrated into
      clinical practice over time and have also focused on attitudes and used a range
      of teaching methods, have been shown to be effective. A study was set up to
      evaluate whether a communication skills course which would focus on knowledge,
      attitudes and skills would improve nurses' communication skills. One-hundred-and
      ten nurses completed a 26 h training programme over six months and completed
      precourse and postcourse audiotape recordings of a patient assessment. An overall
      statistically significant improvement in assessment skills between pretest and
      post-test mean total scores (P < 0.001) was found, with statistically significant
      improvements in six of the nine key areas assessed. The nurses reported that
      although some elements of the programme, such as role play, had been stressful
      they felt more confident in handling difficult situations. The longer integrated
      communication skills programme which allows nurses to explore attitudes, raise
      self-awareness and develop knowledge and skills appears to be effective.

PMID- 9616456
TI  - Access to palliative medicine training for Canadian family medicine residents.
AB  - The authors conducted a nine-item mail questionnaire of the 16 Canadian family
      medicine teaching programme directors to determine the accessibility and
      operation of palliative care education for their respective family medicine
      residents. All 16 faculties of medicine responded (100%). The survey revealed
      that while all universities offer elective time in palliative care only five out
      of 16 (31%) have a mandatory rotation. The median durations of the mandatory and
      elective rotations are limited to two and three-and-a-half weeks, respectively.
      The majority of the universities offer formal lectures in palliative care (12/16,
      75%) and educational reading material (13/16, 81%), with the main format in 14/16
      (87%) of the sites being case-based learning. The two most common sites for
      teaching to occur for the residents are the community/outpatient environment and
      an acute palliative care unit. Fifty-six per cent (9/16) of the universities have
      designated faculty positions for palliative medicine with a median number of two
      positions per site. Only one centre offers a specific palliative medicine
      examination during the rotation. Feedback from the residents regarding their
      respective palliative medicine programmes were positive overall. Findings from
      our survey indicate an ongoing need for improved education in palliative medicine
      at the postgraduate level.

PMID- 9616457
TI  - Quality of life of cancer patients and their spouses in palliative home care.
AB  - Incurable ill cancer patients (n = 37) and their spouses, while receiving support
      from a hospital-based palliative service, were assessed monthly regarding quality
      of life, using the assessment of quality of life at the end of life instrument.
      Lowest ratings for patients during the final six weeks were found in the
      following items: ability to do what one wants, physical strength, global quality
      of life, and meaningfulness. The pain situation was stable over time. Generally,
      patients were less anxious than spouses. The least-optimal items at the end of
      life for the patients' partners were: ability to leave the patients unattended,
      need for assistance with hygiene/dressing and anxiety. Meaningfulness was the
      item with the strongest correlation to global quality of life, for both patients
      and spouses. A more ambitious approach to the existential domain appears to be
      essential if we wish to optimize quality of life for patients within palliative
      care.

PMID- 9616458
TI  - Evaluation of a hospital-based palliative support service with particular regard
      to financial outcome measures.
AB  - The object of this study was a financial assessment of a hospital-based
      palliative support service, to be made by comparing the study group with a
      matched historical control group and a group of contemporary reference patients.
      The staff consisted of one full-time nurse supported by a surgeon one half-day
      per week. The patients in the study group utilized fewer institutional days than
      the control group, according to such parameters as duration of terminal
      hospitalization (P < 0.05), ratio of days at home to total inclusion days (P <
      0.001), and days at home during last two months of life (P < 0.01). These three
      outcome measures all focus on the most care-intensive last months of life and
      appeared to be sensitive enough to identify economic advantages of palliative
      care intervention. The palliative support service defrayed its own costs and in
      excess of that saved another SK17000 per patient (US$2500).

PMID- 9616459
TI  - An audit of place of death of cancer patients in a semi-rural Scottish practice.

PMID- 9616460
TI  - Benzonatate for opioid-resistant cough in advanced cancer.
AB  - Chronic cough is a distressing symptom experienced by approximately 37% of
      patients with advanced cancer. Palliation of chronic nonproductive cough should
      always first address the underlying cause but in some patients chronic,
      nonproductive cough persists and antitussive agents are required. Opioids are the
      gold standard cough suppressants, of which codeine is the most widely used;
      patients with an opioid-resistant cough often prove to be a therapeutic
      challenge. We report three patients with an opioid-resistant cough who achieved
      symptomatic relief with the peripherally acting nonopioid drug benzonatate.

PMID- 9616461
TI  - The patulous Eustachian tube syndrome.

PMID- 9616462
TI  - Opioid rotation: does it have a role?

PMID- 9616463
TI  - Opioids, confusion and opioid rotation.

PMID- 9616464
TI  - Topical morphine in Ayurveda.

PMID- 9616465
TI  - Colour in a larger perspective: the rebirth of Gestalt psychology.
AB  - This overview takes the reader from the classical contrast and assimilation
      studies of the past to today's colour research, in a broad sense, with its
      renewed emphasis on the phenomenological qualities of visual perception. It shows
      how the shift in paradigm from local to global effects in single-unit recordings
      prompted a reappraisal of appearance in visual experiments, not just in colour,
      but in the perception of motion, texture, and depth as well. Gestalt ideas placed
      in the context of modern concepts are shown to inspire psychophysicists,
      neurophysiologists, and computational vision scientists alike. Feedforward,
      horizontal interactions, and feedback are discussed as potential neuronal
      mechanisms to account for phenomena such as uniform surfaces, filling-in, and
      grouping arising from processes beyond the classical receptive field. A look
      forward towards future developments in the field of figure-ground segregation
      (Gestalt formation) concludes the article.

PMID- 9616466
TI  - Neon color spreading: a review.

PMID- 9616467
TI  - Color from motion: dichoptic activation and a possible role in breaking
      camouflage.
AB  - 'Color from motion' describes the perception of a spread of subjective color over
      achromatic regions seen as moving. The effect can be produced in a display of
      multiple frames shown in quick succession, each frame consisting of a fixed,
      random placement of colored dots on a high-luminance white background with color
      assignments of some dots, but not dot locations, changing from frame to frame.
      Evidence is presented that the perception of apparent motion and the spread of
      subjective color can be activated by binocular combination of disjoint signals to
      each eye. The dichoptic presentation of every odd-numbered frame of the full
      stimulus sequence presented to one eye and, out of phase, every even-numbered
      frame to the other eye produces a compelling perception of color from motion
      equal to that seen with the full sequence presented to each eye alone. This is
      consistent with the idea that color from motion is regulated in sites at or
      beyond the convergence of monocular pathways. When the background field in the
      stimulus display is of low luminance, an amodally complete object, fully colored
      and matching the dots defining the moving region in hue and saturation, is seen
      to move behind a partially occluding screen. Observers do not perceive such an
      object in still view. Hence, color from motion can be used by the visual system
      to produce amodal completion, which suggests that it may play a role in enhancing
      the visibility of camouflaged objects.

PMID- 9616469
TI  - A functional role for illusory colour spreading in the control of focused visual
      attention.
AB  - In cases of modal completion, illusory colour spreading fills in the surface of a
      subjectively completed shape. In amodal completion, shapes are likewise
      completed, but now behind a partial occluder, so that filling in of illusory
      colour to the completed region no longer arises. We consider the possible
      functional effects that illusory colour spreading may exert on later stages of
      vision, and argue that comparisons of modal with amodal completion may be
      particularly revealing in this regard. It is hypothesised that cueing the
      inducers of a modally completed object should attract attention to the entire
      object, including the completed region, owing to the colour spreading there. By
      contrast, changes to the inducers of a comparable amodally completed object
      should only attract attention to the inducing regions themselves. This prediction
      is supported by findings in two experiments with stereoscopic displays, with
      control conditions ruling out nonattentional accounts, or explanations in terms
      of stereo disparity alone rather than the presence versus absence of illusory
      colour. We argue that illusory colours get filled in at quite early stages during
      modal completion, precisely so that later stages of vision, such as focused
      attention, can then be driven by the completed regions in the same way as for
      uniform regions that are physically present in the image.

PMID- 9616468
TI  - Color from motion: separate contributions of chromaticity and luminance.
AB  - 'Color from motion' describes the perception of a spread of subjective color over
      achromatic regions seen as moving. The effect is produced with a stimulus display
      consisting of colored dots, randomly placed upon a white field, with dots in the
      test region differing in both chromaticity and luminance from those in the
      surround. Evidence is presented suggesting that color from motion may be
      regulated by mechanisms different from those for contour formation and color
      contrast. (1) Results based on ratings show that, in the absence of luminance
      differences between the dots in the test and those in the surround regions,
      chromaticity differences alone are sufficient to produce color spread from
      motion. As the equiluminance point is approached, subjective color spread is seen
      despite a reduction in the strength of the subjective contour. Thus, contour
      formation is not likely to be a prerequisite for color from motion. (2) Color
      matches show that the hue and saturation of the subjective color spread are
      determined largely by the chromaticity and the luminance of the dots in the test
      region, not by those of the dots in the surround for the values explored. This
      suggests that color from motion may arise in sites distinct from those
      responsible for the regulation of color contrast.

PMID- 9616470
TI  - Moving stimuli define the shape of stationary chromatic patterns.
AB  - A study is reported of phenomena involved in perceptually unified organisation of
      a stationary chromatic pattern and a moving black outline or dot pattern. When
      the corners of the outline pattern were temporally oscillated on a stationary
      chromatic square, the chromatic border appeared to follow the moving outline, as
      if captured by it. This capture effect was also observed with moving dots: the
      chromatic border was defined by an imaginary line connecting the moving dots.
      Both capture effects occur over a region that becomes wider with increasing
      velocity of the oscillation. These observations suggest that the visual system
      effectively uses information from moving features to define the shape of
      overlapping chromatic image regions.

PMID- 9616471
TI  - The Craik-O'Brien-Cornsweet illusion in colour: quantitative characterisation and
      comparison with luminance.
AB  - The strength of the Craik-O'Brien-Cornsweet illusion was measured for different
      values of spatial and temporal stimulus parameters, in the traditional achromatic
      version, and in an isoluminant colour version. It was found that the illusion is
      much weaker with isoluminant colour stimuli than with achromatic luminance
      stimuli. The illusion depends on the spatial parameters of the stimulus in a way
      that yields an approximate scale invariance: The strength of the illusion is
      similar for different stimulus sizes, as long as the ratio of the width of the
      transition region around the edge, where luminance or colour change, to the total
      stimulus width is preserved. In both the achromatic and the chromatic case, the
      strength of the illusion decreases with increasing presentation time. The
      similarity of the differences between brightness and colour effects on one hand
      and the differences in sensitivity for colour and luminance changes in humans on
      the other suggests that a lack of gradient detection underlies the Craik-O'Brien
      Cornsweet illusion.

PMID- 9616472
TI  - The effect of inducer polarity and contrast on the perception of illusory
      figures.
AB  - A study designed to determine how inducer-surround contrast and inducer polarity
      affect the contour clarity and the lightness of illusory figures is reported.
      Using magnitude estimation procedures, ten naive subjects rated both the contour
      clarity and the lightness of Kanizsa squares. The magnitude of the inducer
      surround contrast and the inducer polarity (all-black, all-white, or black-and
      white) were varied randomly on each trial. The data indicate that contour clarity
      increases with contrast at the same rate across polarity conditions but that
      contour clarity at any given contrast level depends significantly on polarity.
      Contour clarity judgments were significantly lower when the inducers were all
      white than when the inducers were all-black or black-and-white, and significantly
      greater in the 'mixed' polarity case (black-and-white inducers) than in the
      'same' polarity case (the average of the all-black and all-white inducer
      conditions). Inducer contrast and polarity significantly affected the lightness
      of the illusory figure in a manner consistent with simultaneous spatial contrast.
      Also, for a given increment in contrast, contour clarity altered significantly
      more than surface lightness, regardless of inducer polarity. The findings suggest
      that the mechanism which mediates boundary formation is sensitive to the
      direction of contrast, and that the boundary formation mechanism is more
      sensitive than the surface lightness mechanism to changes in contrast magnitude.
      The results are considered within the context of neural network models of form
      perception.

PMID- 9616473
TI  - Interpolation processes in the perception of real and illusory contours.
AB  - The spatial and temporal characteristics of mechanisms that bridge gaps between
      line segments were determined. The presentation time that was necessary for
      localisation and identification of a triangular shape made up of pacmen, pacmen
      with lines, lines, line segments (corners), or pacmen with circles (amodal
      completion) was measured. The triangle was embedded in a field of distractors
      made up of the same components but at random orientations. Subjects had to
      indicate whether the triangle was on the left or on the right of the display
      (localisation) and whether it was pointing upward or downward (identification).
      Poststimulus masks consisted of pinwheels for the pacmen stimuli or wheels
      defined by lines. Stimuli were presented on a grey background and defined by
      luminance or isoluminant contrast. Thresholds were fastest when the triangle was
      defined by real contours, as for the pacmen with lines (105 ms) and the lines
      only (92 ms), slightly slower for corners (118 ms) and pacmen (136 ms), and much
      slower for the amodally completed pacmen (285 ms). For all inducer types
      localisation was about 20 ms faster than identification. In a second experiment
      the relative length of the gap between inducers was varied. Thresholds increased
      as a function of gap length, indicating that the gaps between the inducers need
      to be interpolated. There was no significant difference in the speed of this
      interpolation process between the pacman stimuli and the line-segment stimuli.
      About 40 ms were required to interpolate 1 deg of visual angle, corresponding to
      about one third of the distance between inducers. In a third experiment, it was
      found that processing of isoluminant stimuli was as fast as for low-contrast
      luminance stimuli, when targets were defined by real contours (lines), but much
      slower for illusory contours (pacmen). The conclusion is that the time necessary
      to interpolate a contour depends greatly on the spatial configuration of the
      stimulus. Since interpolation is faster for the line-segment stimuli, which do
      not elicit the percept of an illusory contour, the interpolation process seems to
      be independent of the formation of illusory contours.

PMID- 9616474
TI  - Surface completion complements boundary interpolation in the visual integration
      of partly occluded objects.
AB  - Previous research on perceptual completion has emphasized how the spatial
      relationships of edges influence the visual integration of the image fragments
      that result from partial occlusion. We report studies testing the hypothesis that
      the similarity of surface features also influences visual integration,
      complementing edge interpolation processes. Using displays that separated edge
      interpolation processes from surface-feature interpolation processes, we tested
      the hypotheses that a surface completion process integrates image fragments with
      similar surface features, and that surface completion is constrained by amodally
      interpolated and amodally extended boundaries. Both edge relatability and surface
      feature similarity were manipulated in a series of paired-comparison and
      classification tasks. The results of these studies supported the hypotheses and
      were extended to surface features of colors, textures, and color gradients.
      Results also suggest that, under certain conditions, surface completion may
      interact with and influence edge interpolation.

PMID- 9616475
TI  - Gaps in perception.

PMID- 9616476
TI  - Frame-of-reference and hierarchical-organisation effects in the rod-and-frame
      illusion.
AB  - Two hypotheses proposed as alternatives by Rock--frame of reference and
      hierarchical organisation of perception--were tested in a series of experiments
      with the use of the rod-and-frame illusion. This illusion produces errors in the
      apparent vertical due to the presence of a tilted frame surrounding the test rod.
      The apparent vertical is shifted in the direction of the frame tilt. When an
      upright square was added inside the tilted frame, rod-setting errors varied
      according to the visual characteristics of the display. In the case of a large
      display presented in the dark (experiment 1), there continued to be large errors
      in the direction of the outer-square tilt. This finding supports the frame-of
      reference hypothesis, which proposes that the orientation of all objects in the
      visual field is dominated by the most peripheral reference. In the case of a
      small display presented in a lit environment (experiments 2 and 3), the direction
      of errors was the opposite. This latter finding was taken to indicate that the
      rod was set with reference to the perceived tilt of the inner upright square.
      Thus, according to a hierarchical-organisation hypothesis, the orientation of an
      object in the visual field is influenced by objects in the immediate surroundings
      not by outermost reference. Overall, the results confirm the presence of two
      qualitatively different classes of orientational phenomena: one is concerned with
      the definition of egocentric coordinates and one with an object-centred visual
      representation.

PMID- 9616477
TI  - Real and virtual borders in the Poggendorff illusion.
AB  - The strength of the Poggendorff illusion has been determined by a nulling method
      for the classical as well as other configurations of the central inducing region.
      Compared to a uniform field, an inducing rectangle with very low contrast
      produces a marked illusion, which saturates at a Michelson contrast of about 0.1.
      With virtual borders of the Kanizsa type there is a weak illusion and this effect
      is attenuated when the 'pacman' sectors are occluded. Texture borders without
      luminance contrast induce a stronger illusion. These results are discussed in
      relation to earlier data for contrast dependence of Vernier acuity and for the
      orientation discrimination and tilt illusion with real and virtual borders.

PMID- 9616478
TI  - Types of size disparity and the perception of surface slant.
AB  - We examined (i) perceived slant of a textured surface about a vertical axis as a
      function of disparity magnitude for horizontal-size disparity, vertical-size
      disparity, and overall-size disparity; and (ii) interactions between patterns
      with various types and magnitudes of size disparity and superimposed or adjacent
      zero-disparity stimuli. Horizontal-size disparity produced slant which increased
      with increasing disparity, was enhanced by superimposed zero-disparity stimuli,
      and induced contrasting slant in superimposed or adjacent zero-disparity stimuli.
      Vertical-size disparity produced opposite slant (induced effect) which was
      reduced to near zero by a superimposed zero-disparity pattern and both patterns
      appeared as one surface. Adjacent vertical-size-disparity and zero-disparity
      patterns appeared as separate surfaces with a wide curved boundary. Overall-size
      disparity produced slant which was enhanced by a superimposed zero-disparity
      pattern and less so by a zero-disparity line, and induced more slant in a zero
      disparity line than in a zero-disparity pattern. The results are discussed in
      terms of depth underestimation of isolated surfaces, depth enhancement, depth
      contrast, and the processing of deformation disparity.

PMID- 9616479
TI  - Steering without representation with the use of active fixation.
AB  - This paper demonstrates the use of active fixation on both fixed and moving
      fixation points to guide a robot vehicle by means of a steering rule which, at
      large distances, sets the steering angle directly proportional to the deviation
      of gaze direction from translation direction. Steering a motor vehicle around a
      winding but otherwise uncluttered road has been observed by Land and Lee to
      involve repeated periods of visual fixation upon the tangent point of the inside
      of each bend. We suggest that proportional rule devised for steering in the
      robotic example appears applicable to the observed human performance data,
      providing an alternative explanation to the quadratic rule proposed by Land and
      Lee.

PMID- 9616480
TI  - Motion parallax: effects of blur, contrast, and field size in normal and low
      vision.
AB  - Can people with different forms of low vision use motion parallax to improve
      depth judgments? We used a staircase method to compare depth thresholds using
      motion parallax and static viewing. We tested eighteen normal-vision subjects
      with a range of simulated deficits in acuity, contrast sensitivity, and simulated
      peripheral-field loss, and ten low-vision subjects with a wide range of acuity,
      contrast sensitivity, and field loss. Subjects viewed three vertical cylinders
      monocularly and indicated which one was at a different depth from the other two.
      For motion-parallax trials, observers moved their heads (in a viewing assembly on
      rollers) from side to side over a range of 6-12 cm. For static trials, the
      viewing assembly was fixed in place. Normal-vision subjects' depth thresholds
      with motion parallax were significantly smaller than those with static viewing by
      an average factor of 1.95 (p < 0.05) across all levels of acuity and contrast.
      For low-vision observers, the depth thresholds exhibited large individual
      differences; however, the motion-parallax thresholds were smaller than the static
      thresholds by an average factor of 2.05 (p < 0.01). These findings indicate that
      motion parallax can provide useful depth information for people with low vision.

PMID- 9616481
TI  - Perception of biological motion.
AB  - Boundary conditions for perception of biological motion were explored with the
      use of computer-generated point-light animation sequences. Perception of this
      unique form of structure from motion is immune to variations in dot contrast
      polarity, dot disparity, and spatial-frequency filtering. Biological motion is
      perceived in texture-defined animation sequences that presumably stimulate only
      second-order motion pathways, and it is undisturbed by dichoptic presentation of
      portions of the animation tokens separately to the two eyes.

PMID- 9616482
TI  - Paradoxical rest.
AB  - Paradoxical absence of motion in a rotating pattern is reported. The effect
      requires that the motion of the paradoxically stationary figure be underspecified
      by local motion signals, and that the paradoxically stationary figure be well
      segregated. This is consistent with proposals that figural segregation affects
      the integration of local motion signals.

PMID- 9616483
TI  - Face detection in peripheral vision: do faces pop out?
AB  - We examined whether faces can produce a 'pop-out' effect in visual search tasks.
      In the first experiment, subjects' eye movements and search latencies were
      measured while they viewed a display containing a target face amidst distractors.
      Targets were upright or inverted faces presented with seven others of the
      opposite polarity as an 'around-the-clock' display. Face images were either
      photographic or 'feature only', with the outline removed. Naive subjects were
      poor at locating an upright face from an array of inverted faces, but performance
      improved with practice. In the second experiment, we investigated systematically
      how training improved performance. Prior to testing, subjects were practised on
      locating either upright or inverted faces. All subjects benefited from training.
      Subjects practised on upright faces were faster and more accurate at locating
      upright target faces than inverted. Subjects practised on inverted faces showed
      no difference between upright and inverted targets. In the third experiment,
      faces with 'jumbled' features were used as distractors, and this resulted in the
      same pattern of findings. We conclude that there is no direct rapid 'pop-out'
      effect for faces. However, the findings demonstrate that, in peripheral vision,
      upright faces show a processing advantage over inverted faces.

PMID- 9616484
TI  - Viscosity discrimination: a comparison of an adaptive two-alternative forced
      choice and an adjustment procedure.
AB  - Differential thresholds for viscosity were measured in ten subjects with the use
      of an adaptive two-alternative forced-choice procedure. An electromagnetic linear
      motor was connected to each wrist and the viscosity of the motors was under
      computer servo control. For each block of 50 trials the viscosity of one motor
      was fixed at a reference value which ranged from 4 to 512 N s m-1, and the
      viscosity of the other motor varied according to the subject's responses. On each
      trial subjects were required to indicate which motor had the greater viscosity
      and were given feedback of the correct response. By this procedure the Weber
      fraction for viscosity was calculated to be 19%, which is lower than the Weber
      fraction of 34% estimated by using the method of adjustment. The criterion used
      for determining the threshold differs in the two procedures (71% and 84% correct,
      respectively), and the results from the two studies were found to be consistent.
      They suggest that the Weber fraction for viscosity remains remarkably stable
      despite differences in the methods of measurement.

PMID- 9616485
TI  - On Ptolemy's geometry of binocular vision.

PMID- 9616486
TI  - Disease-associated malnutrition in the year 2000.
AB  - Malnutrition is associated with increased morbidity and mortality and is common
      in patients admitted to hospital. Nutritional status is not routinely assessed on
      admission, and nutritional depletion escapes recognition in the majority of
      affected patients. Nutritional status declines during hospital stay, and this
      trend is most marked in patients who are already malnourished on admission.
      Techniques for nutritional support are available, their appropriate use leads to
      improved nutritional status and clinical outcome in most patients. There is
      evidence that the current use of artificial nutrition is suboptimal and
      associated with a high complication rate. The introduction of clinical guidelines
      and the formation of nutrition support teams will improve nutritional management
      in the future. The development of new substrates and 'pharmaconutrition' is
      likely to further improve the outcome for many patients. There will remain a need
      for more studies to define the cost efficacy of artificial nutrition across a
      broad spectrum of clinical practice.

PMID- 9616487
TI  - The neuroleptic malignant syndrome: a logical approach to the patient with
      temperature and rigidity.
AB  - The neuroleptic malignant syndrome is a rare, potentially fatal, adverse reaction
      to neuroleptic drugs characterised by severe rigidity, high temperature and
      autonomic dysfunction. In the light of the hypothesized pathophysiology of this
      condition, a rational approach to the management of patients presenting with
      temperature and rigidity is provided. The aims of this approach are three-fold:
      to reduce the incidence of the condition, to be able to recognise it early so as
      to treat before life-threatening complications arise, and to be able to recognise
      early those conditions which mimic neuroleptic malignant syndrome, so as not to
      delay their specific treatment.

PMID- 9616488
TI  - Cell and molecular mechanisms of pathogenesis and treatment of cancer.
AB  - Surgery remains the mainstay of treatment for most classes of human solid
      tumours, with the principal exception of lymphomas, but it is insufficient in
      many cases to guarantee cure. With few exceptions, recurrent and metastatic solid
      tumours continue to defy attempts to develop effective adjuvant therapies. Recent
      insights into tumour biology reveal an increasingly complex picture of cell and
      molecular processes which confer heterogeneity and resistance to treatment upon
      tumours. These insights may also yield new targets for more effective adjuvant
      therapies.

PMID- 9616489
TI  - Interprofessional learning.
AB  - Effective care in hospitals and in the community requires doctors, nurses and
      other healthcare professionals to work together to achieve the best possible
      outcomes for patients. In the UK, a shift in emphasis towards a primary care led
      service and recent changes to the ways in which healthcare is funded and
      organised, are profoundly affecting traditional patterns of working. Boundaries
      which define the roles and responsibilities of individual professions are
      becoming less clear and there is increasing overlap of knowledge and skills. The
      provision of effective patient care now depends much more on the individual
      practitioner's understanding of the need to collaborate within and between
      healthcare teams in community settings and the care provided in hospitals. This
      paper describes some of the ways in which those providing education and training
      for the professions are seeking to create opportunities for learners which will
      not only help them to understand the complexities of working in a
      multiprofessional healthcare environment, but also enable them to develop the
      skills and attitudes they need for interprofessional working. However, it is not
      yet established whether 'learning together' during basic training will result in
      better 'working together' in practice. Higher education institutions are
      understandably cautious about adopting new learning methods which make extra
      demands on decreasing resources. More studies are therefore needed to show
      whether interprofessional learning during basic education has an impact on future
      working practice.

PMID- 9616490
TI  - Unravelling the helix--a physician's guide to spiral computed tomography.
AB  - The introduction of spiral technology to computed tomography (CT) scanners in the
      late 1980s has revolutionised the field of CT. Spiral CT offers definite
      practical benefits over conventional scanners and has expanded the role of CT
      through the development of new scanning techniques. CT scanning now rivals
      magnetic resonance imaging in many areas of investigation, and for some
      situations is the clear investigation of choice. This review is aimed at those
      clinicians who have access to spiral scanning services but wish to have a greater
      understanding of the technique and its clinical applications. The concept of
      spiral CT, and the differences between spiral and conventional scanning are
      discussed. The various clinical applications of the technique are illustrated.

PMID- 9616491
TI  - Characteristics of patients with shingles admitted to a district general
      hospital.
AB  - Little is known about why some patients with shingles are admitted to hospital.
      We reviewed 72 case notes from a list of 80 patients admitted to hospital with
      shingles over a six-year period. Pain was the main complaint of the patients
      admitted, most of whom were elderly and lived alone. The commonest site of
      involvement in hospital admissions was the eye (herpes zoster ophthalmicus).
      Diagnosis of shingles was made after admission in 12 patients, eight of whom had
      originally been diagnosed as having an acute medical or surgical condition. We
      conclude that the prodromal phase of shingles may lead to misdiagnosis.

PMID- 9616492
TI  - Complications associated with different insertion techniques for Hickman
      catheters.
AB  - A dependable central venous access is an essential prerequisite for the delivery
      of care to the cancer patients. This has become easier since the introduction of
      indwelling central venous catheters. However, pancytopenia, often encountered in
      haematological malignancies, does influence the morbidity associated with these
      catheters. In this study the effects of two different placement techniques of
      Hickman catheters were evaluated. A total of 177 Hickman catheters were inserted
      in patients suffering from haematological malignancies. In 112 patients the
      catheters were placed percutaneously into subclavian veins without prior
      tunnelling; in the other 65 patients these were introduced, after having been
      tunnelled, into cephalic/external jugular veins by a cut-down technique. The
      catheters remained in use in each patient for between 18 and 253 days. Excessive
      bleeding and haematoma formation occurred in a significantly higher proportion of
      patients from the cut-down group (61% and 41%, respectively) compared to patients
      from the percutaneous group (8% and 0%, respectively). These in turn had a
      profound impact on the incidence of infective complications. Catheter exit site
      infection, tunnel infection and septicaemia were observed in 26%, 18%, and 41%,
      respectively, of the patients from the cut-down group, while in patients from the
      percutaneous group, skin exit site infection was noted only in 7% and septicaemia
      in 19% of patients. It was concluded that the placement technique of these
      catheters exerts a significant influence on the immediate as well as delayed
      complications. The results indicate that the insertion technique requiring
      minimal dissection is more beneficial. It is therefore recommended that
      percutaneous insertion without tunnelling should be the technique of choice for
      catheter placement.

PMID- 9616493
TI  - Ectopic Cushing's syndrome and pulmonary carcinoid tumour identified by [111In
      DTPA-D-Phe1]octreotide.
AB  - The differential diagnosis and management of Cushing's syndrome remain difficult,
      particularly for ectopic adrenocorticotropin (ACTH) syndromes resulting from
      small bronchial carcinoids. We report the case of a 41-year-old man with ectopic
      ACTH-dependent Cushing's syndrome. Two computed tomography scans of the thorax
      were normal and magnetic resonance imaging of the chest showed a 6-mm
      hyperintense T1-weighted area close to the left pulmonary hilus, interpreted as
      probably vascular by the radiologists. An [111In-DTPA-D-Phe1]octreotide
      scintigraphy scan demonstrated a positive image for somatostatin receptors in
      exactly the same location and surgery confirmed the presence of a small ACTH
      secreting carcinoid tumour in the upper left lung lobe which was resected.
      Surgery cured the hypercorticism of the patient. The differential diagnosis of
      Cushing's syndrome and the procedure for localisation of an ACTH source are
      discussed.

PMID- 9616494
TI  - Rapid recurrence of pulmonary hypertension following cessation of nifedipine.
AB  - In a young woman with primary pulmonary hypertension, treatment with low-dose
      nifedipine resulted in resolution of symptoms and of tricuspid regurgitation. On
      withdrawal of nifedipine, symptomatic pulmonary hypertension recurred within 48
      hours and was controlled by reintroduction of low-dose nifedipine.

PMID- 9616495
TI  - First-aid treatment of epistaxis--confirmation of widespread ignorance.
AB  - A survey of 500 members of the public was carried out in which they were asked
      how they would deal with a nose bleed. Only 50 out of 443 responses were judged
      as being correct, confirming a clinical impression, long held by those dealing
      with epistaxis, that there is a high level of ignorance as to the correct first
      aid treatment. The survey also suggested that the lack of knowledge was not
      confined to the general public but evident in those trained in healthcare.

PMID- 9616496
TI  - Chest pain in a young girl.

PMID- 9616497
TI  - Ovarian carcinoma producing hypoglycaemia.

PMID- 9616498
TI  - Skeletal abnormalities, hypocalcaemia and intracranial calcification.

PMID- 9616499
TI  - An overweight woman with galactorrhoea.

PMID- 9616500
TI  - Bipolar affective disorder, stress fractures, fungal dermopathy and 'tree frog
      fingers'.

PMID- 9616501
TI  - Ticlopidine-induced severe neutropenia.

PMID- 9616502
TI  - Sarcoidosis: historical perspective and immunopathogenesis (Part I).

PMID- 9616503
TI  - Sarcoidosis: clinical manifestations, staging and therapy (Part II).

PMID- 9616504
TI  - Health habits and illness behaviour: social factors in patient self-management.

PMID- 9616505
TI  - Ventilation in a Birmingham intensive care unit 1993-1995: outcome for patients
      with chronic obstructive pulmonary disease.
AB  - The aims of the study were to look at information on which the decision to
      ventilate chronic obstructive pulmonary disease (COPD) patients admitted to an
      intensive care unit (ITU) was based (including whether there was discussion with
      the patient, relatives and consultant), to identify indicators of poor prognosis,
      and to assess the outcomes of ventilation and functional capacity after
      discharge. A retrospective study of 27 months of admissions was carried out. The
      following variables were studied to see if they influenced prognosis: premorbid
      history, admission diagnosis, consultant involvement in the decision to transfer
      to ITU, admission chest radiograph, sputum bacteriology, arterial blood gases,
      APACHE II scores, duration of ventilation and complications in ITU. In-hospital
      mortality, post-discharge mortality and length of hospital stay were recorded.
      Functional capacity after discharge was assessed from the hospital clinic records
      and from general practitioners. Forty-six percent of case notes had inadequate
      premorbid information and no documented discussion occurred in 66% of
      patients/relatives. Poor prognostic indicators were admissions after
      cardiorespiratory arrest, cases discussed with consultants regarding ITU
      transfer, previous therapy with long-term oral steroids, and developing renal or
      cardiac failure in ITU. APACHE II scores were higher in the group that died.
      There was 49% hospital mortality and 59% 1-year mortality. Fifty-three percent of
      survivors were dependent upon carers and housebound, and general practitioners
      felt that 59% of survivors had a higher dependence on carers, a worse exercise
      tolerance and a poorer quality of life than before admission. The decision to
      ventilate is often made with inadequate background history, which could be sought
      from general practitioners, hospital case notes and family. There is significant
      morbidity and mortality following ventilation. Further prospective studies are
      required to help select which COPD patients should be ventilated.

PMID- 9616506
TI  - Budesonide but not terbutaline decreases phagocytosis in alveolar macrophages.
AB  - Alveolar macrophages are the most common cells in bronchoalveolar lavage fluid.
      The macrophages participate in the inflammatory response and defence of the
      airways by secretion of mediators and by phagocytizing foreign particles such as
      bacteria and viruses. beta-Agonists and glucocorticosteroids are the most
      frequently used drugs in asthma. Alveolar macrophages have beta 2-adrenoceptors
      on their surface but the functional role of these receptors is unknown.
      Glucocorticosteroids interact with mediator release from macrophages. However,
      nothing is known about the effects of those drugs on the phagocytic capacity of
      alveolar macrophages. Therefore, the present study has investigated phagocytosis
      of alveolar macrophages from nine healthy volunteers after incubation with a beta
      2-agonist, terbutaline (10(-8), 10(-6) and 10(-4) M) and a glucocorticosteroid,
      budesonide (10(-9), 10(-7) and 10(-5) M). Alveolar macrophages were incubated
      with FITC-labelled Escherichia coli, and the drugs and phagocytosis was assessed
      by flow cytometry. Phagocytosis was measured as the proportion of phagocytizing
      cells and mean fluorescence intensity (MFI). MFI was highly correlated with
      phagocytized E. coli per cell assessed by fluorescence microscopy (r = 0.996).
      The proportion of phagocytizing macrophages (control) was [median (25th-75th)
      percentiles] 46% (40-63) and 29% (18-60), and MFI were 174 (154-205) and 122 (90
      271) in the terbutaline and budesonide experiments, respectively. Terbutaline did
      not affect the phagocytosis significantly, while budesonide decreased the
      phagocytic capacity (percent phagocytizing cells and MFI) in a dose-dependent
      manner (P < 0.01). At the highest budesonide concentration (10(-5) M),
      phagocytosis was approximately half of the control situation. In conclusion, this
      in vitro study indicate that a glucocorticosteroid decreases phagocytosis in
      alveolar macrophages in a concentration that may be relevant in the airway lining
      fluid. Further investigations regarding the effect on other micro-organisms and
      in vivo effects are necessary to further elucidate these findings.

PMID- 9616507
TI  - Beta 2-agonists administered by a dry powder inhaler can be used in acute asthma.
AB  - Patients with acute asthma attending the emergency room were included in a double
      blind, double-dummy and parallel group study to investigate whether a dry powder
      inhaler (Turbuhaler) can be used in acute asthma. If so, the aim was to establish
      the potency relationship between a beta 2-agonist (salbutamol) administered by
      the dry powder inhaler and the pressurized metered-dose inhaler (pMDI). Eighty
      six patients with a mean age of 38 years and forced expiratory volume in 1 s
      (FEV1) of 37% of predicted normal value were randomized at Siriraj Hospital in
      Bangkok to either Turbuhaler (50 micrograms dose -1) or pMDI (100 micrograms dose
      -1) with spacer (Volumatic). Doses of 100 + 300 + 300 + 300 micrograms salbutamol
      were given at 0, 15, 30 and 45 min via Turbuhaler and repeated at 90, 105, 120
      and 135 min (total dose 2000 micrograms). The same inhalation schedule with
      identical number of doses was used for the pMDI with spacer but in double doses
      (total 4000 micrograms), assuming a dose-potency ratio of salbutamol administered
      via Turbuhaler compared with the pMDI of 2:1. At 85 min after the first dose, 60
      mg prednisolone was given orally. FEV1 was measured 10 min after each dosing.
      Peak inspiratory flow (PIF) through Turbuhaler was measured on each dosing
      occasion. Plasma (P)-salbutamol, serum (S)-potassium concentrations, pulse rate,
      blood pressure and adverse events were recorded. No statistically significant
      differences were observed in the increase in FEV1 between the groups: 55 min (165
      min) after the first dose, the increase was 0.47 l and 47% (0.64 l and 63%) in
      the Turbuhaler group, and 0.46 l and 42% (0.68 l and 65%) in the pMDI group. Mean
      PIF though Turbuhaler was 49 l min -1 (range 26-68) at first inhalation and
      increased to 60 l min -1 (range 38-86). There was no correlation between the
      initial PIF through Turbuhaler and the initial FEV1 response. P-salbutamol and S
      potassium values correlated well. A larger decrease in S-potassium was noticed
      after 75 min in the pMDI group (0.38 mmol l -1) compared with the Turbuhaler
      group (0.23 mmol l -1) (P = 0.02). In conclusion, the use of a dry powder
      inhaler, Turbuhaler, was investigated in the emergency room treatment of acute
      asthma, and was as effective as a pMDI with spacer. Half the dose of salbutamol
      administered via Turbuhaler was as effective as the full dose given via a pMDI
      with spacer.

PMID- 9616508
TI  - Thoracic gas compression profile during forced expiration in healthy and
      asthmatic schoolchildren.
AB  - Gas compression profile may aid in the diagnosis of airway obstruction. However,
      the behavior of this parameter in repeated tests and the deviations in patients
      with bronchial asthma have not been thoroughly described. Thirty-six health
      subjects aged 6-16 years were studied in two test sessions with a pressure/flow
      plethysmograph, and 57 asthmatic patients of similar age were studied once. Three
      volumes of compressed thoracic gas (Vcomp) were obtained: with 25%, 50% and 75%
      of vital capacity (VC) expired. Relative Vcomp was calculated using the actual
      amount of gas remaining in the lungs. Regarding the best and second best
      manoeuvre, coefficient of variation (CoV) in Vcomp ranged from 47 to 79%
      (controls) and from 48 to 112% (patients). Regarding the best manoeuvre in the
      first and second test session (controls), CoV in Vcomp ranged from 73 to 159%.
      Bronchodilator response had an extreme individual variation, and the changes were
      insignificant in both groups. In the paediatric population, the poor
      repeatability of Vcomp invalidates its use in clinical assessment of pulmonary
      function.

PMID- 9616509
TI  - Transmission and prevalence of Burkholderia cepacia in Welsh cystic fibrosis
      patients.
AB  - From 1987 to 1994, 16 of 162 cystic fibrosis (CF) patients attending CF clinics
      at three different hospitals in South Wales, U.K. were found to have respiratory
      secretions colonized with Burkholderia cepacia (B. cepacia). Bacteriological
      typing by polymerase chain reaction (PCR) ribotyping demonstrated seven strains
      of B. cepacia among these 16 CF patients. This typing confirmed that cross
      infection was the mechanism of colonization in six of the nine patients who were
      colonized at the paediatric CF clinic at the University Hospital of Wales in
      Cardiff, and in three of the six patients who were colonized at the adult CF
      clinic at Llandough Hospital in Cardiff (cross-infection rate nine of 16 patients
      or 56%). A search was made for a nosocomial source, with screening of wards and
      clinics. Swabs from fomites produced four positive cultures for B. cepacia. Two
      isolates had the same PCR ribotype as that of the previous CF room occupant. To
      establish prevalence of B. cepacia among CF children living throughout Wales,
      respiratory secretions were cultured from 151 of 186 CF children (age < 16
      years). This failed to demonstrate B. cepacia colonization other than in the CF
      patients already identified.

PMID- 9616510
TI  - Overexpression of p53 protein in interstitial lung diseases.
AB  - The p53 gene is well known as a tumour suppressor gene. In addition, the mutated
      p53 gene is detected in a variety of human cancers including lung cancer, and is
      considered as an oncogene. Lung cancer is also frequently associated with
      interstitial lung diseases. Therefore, it may be possible to hypothesize that
      there might be some abnormality of p53 gene in interstitial lung diseases. This
      work examined the relationship between the p53 protein and gene in lung tissues
      of 28 patients with interstitial lung diseases. Among 28 patients, 13 cases were
      pathologically diagnosed to have usual interstitial pneumonia (UIP), 12 cases
      were diagnosed as having collagen vascular lung diseases, and three cases were
      diagnosed to have a non-specific interstitial pneumonia. Twenty-three tissue
      samples were obtained by open lung biopsy and five samples were taken by autopsy.
      Paraffin-embedded tissues were treated by microwave, and stained with an anti-p53
      antibody (DO7) by the Avidin-Biotin-Peroxidase (ABC) method. In selected
      patients, mutations in exons 5-8 of the p53 gene were also examined by single
      strand conformation polymorphism (SSCP) analysis and DNA sequence. In addition,
      the presence of anti-p53 antibodies in patients' sera was screened for by ELISA.
      Fifteen samples (53.6%) revealed overexpression of the p53 protein in the nuclei
      of alveolar epithelial cells. However, SSCP or sequence analysis, which was
      performed in 13 tissues, showed no mutations in exons 5-8 of the p53 gene. In
      conclusion, p53 proteins were overexpressed in interstitial lung diseases, and
      the expressed p53 protein was considered to be wild-type. This wild-type p53
      protein may play a role in blocking the transformation of proliferative
      epithelial cells.

PMID- 9616511
TI  - Bronchoalveolar lavage causes decrease in PaO2, increase in (A-a) gradient value
      and bronchoconstriction in asthmatics.
AB  - The aims of this study were to (1) record the changes of (arterial oxygen partial
      pressure) PaO2, (arterial carbon dioxide partial pressure) PaCO2, (percentage
      saturation of haemoglobin with oxygen in arterial blood) SaO2 and alveolar
      arterial (A-a) oxygen gradiant resulting from bronchoalveolar lavage (BAL) in
      asthmatic and normal subjects; (2) measure changes in forced expiratory volume in
      1 s (FEV1), vital capacity forced (FVC) associated with BAL; and (3) assess
      possible predictive factors for the degree of hypoxaemia and impairment of
      spirometry resulting from BAL. Bronchoscopy and BAL (150 ml) were performed in 24
      asthmatics and 15 healthy subjects. Serial arterial blood samples (radial artery)
      were obtained in all subjects: T1 and before T2 after local anaesthesia; T3 at
      end of bronchoscopy; T4 after BAL and 5 min, 15 min, 1 h, 2 h, 8 h and 24 h (T5
      T10) after the procedure, FEV1 and FVC were measured immediately before and 5 min
      afer bronchoscopy. Baseline PaO2 was lower in asthmatics (10.2 +/- 0.8 kPa) than
      in healthy subjects (10.8 +/- 0.8). Both groups showed a significant decrease in
      PaO2, and a significant widening in (A-a) oxygen tension gradiant at T3-9, with
      respect to T1 (P < 0.05). PaO2 reached a significantly lower value in asthmatics
      (7.1 +/- 0.6 kPa) than in HS (7.7 +/- 0.5; P < 0.05). In asthmatics, FEV1, FVC
      and the ratio FEV1/FVC decreased significantly after BAL (P < 0.001). In healthy
      subjects, FEV1 and FVC decreased significantly (P < 0.001), whereas FEV1/FVC did
      not. The fall in FEV1 after BAL was significantly greater in asthmatics (32.4 +/-
      10.0%) than in healthy subjects (17.7 +/- 4.6; P < 0.001). Severity of asthma,
      basline FEV1 or initial PaO2 did not predict the degree of hypoxaemia or the fall
      of FEV1. It is concluded that BAL causes more severe hypoxaemia and a greater
      decrease in FEV1 in asthmatics compared to healthy subjects, strongly supporting
      the recommendation of special caution and careful monitoring when BAL is
      undertaken in asthmatics.

PMID- 9616512
TI  - Chest radiography and tuberculosis case-finding in Western Australia.
AB  - A retrospective study to assess the role of chest radiography (CR) in the control
      of tuberculosis (TB) in Western Australia (WA) was carried out by reviewing the
      annual reports from 1948 to 1983 and analysing the records at the Perth Chest
      Clinic (PCC) for a 12-month period in 1992-93. Mass miniature radiography in WA
      was introduced in 1948 and was selective up to 1951, yielding 3.3 cases of active
      TB per 10(3) films and accounting for 18.3% of the total notifications. It became
      a compulsory statewide screening procedure from 1952 to 1972. During this period
      the average yield was 0.7 cases/10(3) films and they accounted for 19.6% of the
      notifications. Thereafter the examination was again selective, detecting 0.2
      cases/10(3) films and accounting for 2.7% of the notifications for 1977-79. From
      1 July 1992 to 30 June 1993, a total of 2456 asymptomatic persons had chest X-ray
      records at the PCC relating to contact tracing (456), positive Mantoux reaction
      (330), pre-employment clearance as child-care workers (616) and application for
      permanent residence (1054). Overall, their X-rays were reported as normal in
      95.4%, abnormal and of clinical significance in 2.7% and abnormal but of no
      significance in 1.9%. Active TB was detected in 0.2%, giving a yield of 2.4
      cases/10(3) films and accounting for 10% of the notifications for the 12-month
      period. This study shows that mass CR, when judiciously applied, can contribute
      significantly to TB case-finding even in low-prevalence countries where the goal
      is the elimination of the disease.

PMID- 9616513
TI  - Prevalence of asthma symptoms in school children in Ankara, Turkey.
AB  - The aim of this study was to determine the prevalence of symptoms suggestive of
      asthma in children aged 7-14 years in Ankara, Turkey. For this purpose, the
      recently developed ISAAC (International Study for Asthma and Allergies in
      Childhood) questionnaire supplemented with six additional questions was issued to
      parents of 3154 primary school children from 12 schools. A separate page with
      questions regarding risk factors was also added to the questionnaire. The
      response rate was 88.3%. The cumulative and 12-month prevalence of wheezing were
      14.4 and 4.7% respectively. The prevalence of physician-diagnosed asthma was
      8.1%. A family history of atopy was found to be the strongest risk factor for
      having ever had wheezing (odds ratio (OR) = 2.89, 95% confidence interval (CI) =
      2.32-3.60), wheezing in the past 12 months (OR = 3.21, CI = 2.21-4.67), and
      severe attack (OR = 2.41, CI = 1.36-4.25). Passive smoking was a risk only for
      having ever had wheezing (OR = 1.33, CI = 1.03-1.76). Increasing age was
      associated with a lower risk of current wheezing (OR = 0.85, CI = 0.81-0.90) and
      severe attack (OR = 0.77, CI = 0.67-0.88). Gender, socio-economic level and pet
      ownership did not appear to be risk factors for asthma-related symptoms. This
      study, the first epidemiological survey in Ankara, Turkey, using the ISAAC
      protocol, clearly shows that symptoms suggestive of asthma, albeit lower than in
      most European countries, are quite common and constitute a major health problem
      in Turkey.

PMID- 9616514
TI  - Failure of CPAP therapy in obstructive sleep apnoea syndrome: predictive factors
      and treatment with bilevel-positive airway pressure.
AB  - Continuous positive airway pressure (CPAP) is the most widely used therapy for
      obstructive sleep apnoea (OSA). Despite its general efficacy, oxygen desaturation
      due to hypoventilation persists in some patients. The present study analysed the
      factors which are associated with this primary failure and, moreover, examined
      the effect of a bilevel positive airway pressure (BiPAP) trial. In a 15-month
      period, 13 patients with OSA (Group A) failed to respond to initial CPAP therapy
      defined by a remaining apnoea/hypopnoea index (AHI) of > or = 5 or a mean
      nocturnal SaO2 < 90%. These patients were compared to an age- and AHI-matched
      control group (Group B) successfully treated by CPAP. A logistic regression
      analysis was performed to identify factors which are associated with initial
      failure to CPAP. Patients of the CPAP-failure group were treated with nasal BiPAP
      in the control mode. These patients were significantly more obese than patients
      of the control group (mean body mass index 44.2 +/- 7.7 vs 31.2 +/- 6.3 kg m-2; P
      < 0.001). PaO2 at rest (P < 0.001) and at exercise (P < 0.005) was significantly
      lower in Group A patients. PaCO2 at rest (P < 0.001) was significantly higher in
      Group A patients and changed for the worse during exercise, whereas it improved
      in the control group. Group A patients spent significantly (P < 0.0001) more time
      with oxygen saturation < 90%. The percentage of time spent at < 90% of SaO2 was
      the only factor which was independently associated with the initial failure of
      CPAP (OR 1.13; 95% CI 1.0-1.2). After 3 months of treatment with BiPAP, the
      patients' blood gas values while awake improved significantly (P < 0.05) for PaO2
      as well as for PaCO2. In conclusion, patients with OSA resistant to initial CPAP
      are morbidly obese with impaired awake blood gas values. The percentage of time
      spent at < 90% of nocturnal SaO2 is independently associated with initial failure
      of CPAP. BiPAP in the control mode is adequate for nocturnal ventilation, and
      improves awake blood gas values.

PMID- 9616515
TI  - Validity of diurnal sleep recording performed by an ambulatory device in the
      diagnosis of obstructive sleep apnoea.
AB  - The objective of this study was to compare the results of oxygen desaturations
      and sleep apnoea during a daytime nap (D) versus nocturnal sleep (N) evaluation,
      recorded by a portable multichannel monitoring device in patients with a clinical
      suspicion of obstructive sleep apnoea (OSA). Two polysomnographic studies were
      performed, by means of the Healthdyne NightWatch System, in 82 subjects (mean age
      57.9 years). No difference was found in the apnoea + hypopnoea index (AHI) and
      mean SaO2 between D and N recordings. At an AHI threshold of 20, in the D
      recordings, compared to the N ones, the sensitivity was 91% and the specificity
      100%. A good correlation was found for AHI and oxygen desaturation index (ODI)
      between the two experimental conditions (r = 0.89 and 0.79, respectively). Our
      study shows that D recordings seem to be accurate for OSA diagnosis in the
      majority of patients with a clinical suspicion of sleep apnoea syndrome.

PMID- 9616516
TI  - Quality of life in severe chronic obstructive pulmonary disease: correlation with
      lung and muscle function.
AB  - Chronic obstructive pulmonary disease (COPD) patients suffer from significant
      impairment in quality of life (QL), but the variables related to this impairment
      are not well known. The aim of this study has been to identify physiological
      parameters related to QL in severe COPD patients undergoing long-term oxygen
      therapy. MATERIALS AND METHODS: We studied 47 COPD patients using long-term
      oxygen therapy (43 men/four women, 65.17 SD 8.21 years, 3.17 SD 2.61 years on
      oxygen). The Nottingham Health Profile (NHP) and activities of daily living (ADL)
      questionnaire were used to measure QL. Subjective assessment of dyspnoea was
      performed using a visual analogue scale. The physiological parameters determined
      were lung function (spirometry, arterial blood gases, lung volumes and carbon
      monoxide diffusing capacity), muscle function (maximum inspiratory and expiratory
      pressures, deltoid muscle and handgrip strength), and nutrition status
      (tricipital skin fold and mid-arm muscle circumference). RESULTS: High ADL (8.32
      SD 6.97) and NHP scores (energy 63.3 SD 40.43, pain 35.11 SD 31.56, emotional
      reactions 43.03 SD 25.13, sleep 51.91 SD 32.75, social isolation 30.64 SD 26.98,
      physical mobility 49.73 SD 24.93) demonstrated clinically significant QL
      impairment in the severe COPD patients studied. Stepwise multiple regression
      analysis found a correlation between lung function and QL. Low FEV1% was
      associated with impairment in energy, physical mobility and social isolation NHP
      scores and ADL score (r = -0.3, P < 0.05). RV/TLC also correlated with ADL and
      social isolation scores (r = 0.3, P < 0.05). Lung function explained 39-45% of
      the variation in these QL dimensions. QL did not correlate with other lung
      function parameters, muscle function or nutrition status. CONCLUSION: COPD
      patients using long-term oxygen suffer from severe QL impairment affecting not
      only energy and mobility but also emotional reactions, social isolation and
      sleep. Lung function is related to energy, mobility and social isolation
      dimensions, but muscle function is unrelated to QL in these patients.

PMID- 9616517
TI  - Medical thoracoscopy, results and complications in 146 patients: a retrospective
      study.
AB  - In a retrospective study the results of medical thoracoscopy in 147 patients were
      reviewed; 136 of the patients had pleural effusion and 11 patients had diffuse
      pulmonary infiltration. All the pleural exudates were initially screened three
      times successively and found to be sterile and without tumour cells. All
      thoracoscopies were performed with local anaesthesia, with the 'open technique',
      and nine different doctors performed the thoracoscopies. The overall diagnostic
      sensitivity was 90.4%. The results demonstrated 62% with malignancy of the
      pleura, and 38% revealed benign pleural diseases, among them 2% with
      tuberculosis. The sensitivity for malignancy was found to be 88% and the
      specificity 96%. The most common primary lung cancer with involvement of the
      pleura was the adenocarcinoma (62%), and the most common metastatic tumour
      originated from the breast (28%). The sensitivity for tuberculosis was 100% and
      the specificity 100%. No mortality was found, and the morbidity was low at about
      0.6% (empyema, pleuro-cutaneous fistula, transcutaneous growth of tumour
      (mesothelioma)). In 64% of the patients the thoracoscopy resulted in treatment
      (pleurodesis, antituberculous treatment, chemotherapy and peroral steroid
      therapy). The medical diagnostic thoracoscopy in local anaesthesia is a simple,
      low-cost investigation with a relatively high diagnostic accuracy, no mortality
      and a low morbidity.

PMID- 9616519
TI  - Intermediate alpha 1-antitrypsin deficiency PiSZ: a risk factor for pulmonary
      emphysema?
AB  - It is well documented that the severe hereditary disorder alpha 1-antitrypsin
      deficiency (alpha 1ATD) PiZZ is a strong risk factor for emphysema, especially
      among smokers, but the role of intermediate alpha 1ATD PiMZ and PiSZ in the
      development of emphysema remains uncertain. In this study, we have evaluated
      mortality and lung function of 94 persons with intermediate alpha 1ATD PiSZ of
      whom 66 were non-index cases, i.e. persons ascertained through family studies.
      The index cases and the non-index cases were similar with respect to sex, age and
      follow-up time, but differed in smoking habits and FEV1. Among the smokers there
      was no significant difference in pack-years between index cases and non-index
      cases. The overall Standardized Mortality Ratio (SMR) was 1.6 (95% confidence
      intervals (CI): 0.8-2.7). For the index cases the SMR was 4.3 (95% CI: 1.9-8.5)
      and for the non-index cases it was 0.8 (95% CI: 0.3-1.8). In the index group six
      patients died of pulmonary emphysema, one of pulmonary fibrosis, and one of colon
      cancer. In the non-index group two died of pulmonary emphysema, two of pneumonia,
      and one of cerebral haemorrhage. The mean initial FEV1% predicted among the index
      cases was 59% compared with 94% among the non-index cases. Based on the analysis
      of the non-index cases it is concluded that only a small fraction of persons with
      the PiSZ phenotype are at increased risk of developing pulmonary emphysema, and
      at an older age than persons with the PiZ phenotype.

PMID- 9616518
TI  - Epithelial cell damage is induced by neutrophil-derived, not pseudomonas-derived,
      proteases in cystic fibrosis sputum.
AB  - Airway histopathological changes in cystic fibrosis (CF) include damage to the
      epithelial tissue and accumulation of polymorphonuclear leukocytes (PMN). Airways
      of CF patients are usually colonized with bacteria such as mucoid Pseudomonas
      aeruginosa (PA). Bacteria and PMN can both release proteolytic enzymes capable of
      causing tissue damage. This study aims to clarify and compare the roles of these
      agents in epithelium damage. Epithelial cell (EC) damage and detachment induced
      by sputum samples from CF or non-CF patients, with and without lung infection,
      were assessed on amnionic EC in an in vitro model of airway epithelium. Protease
      activity was determined using inhibitor profiles, and compared to the proteolytic
      activity of isolated neutrophils and bacteria. Sputa from CF patients and
      infected non-CF patients induced high levels of detachment. PA also induced high
      levels of EC detachment but Staphylococcus aureus and Haemophilus influenzae, two
      other bacteria commonly isolated from CF sputa, induced no detachment.
      Antiprotease inhibition profiles were similar for PMN and sputa-induced EC
      detachment, but different for PA-induced detachment. These results suggest that
      PMN proteolytic enzymes, probably elastase and cathepsin G, are more likely to be
      the inducers of tissue damage in the airways of CF patients than PA proteolytic
      enzymes.

PMID- 9616520
TI  - Delayed referral reduces the success of video-assisted thoracoscopic surgery for
      spontaneous pneumothorax.
AB  - BACKGROUND: Video-assisted thoracoscopic surgery (VATS) is now the generally
      preferred surgical treatment for spontaneous pneumothorax but is more difficult
      once pleural adhesions have developed. To test the hypothesis that VATS is under
      used because of prolonged pleural intubation, we have audited the effect of
      preoperative management on subsequent surgical outcome. METHOD: Data are
      expressed as median (range). A prospective audit of clinical outcome in 42
      consecutive patients (30 male, 12 female, aged 39 [19-81] years) referred to a
      Regional Unit for non-elective pneumothorax surgery. VATS was attempted whenever
      possible. RESULTS: VATS was successful in 32 patients (group V) but 10 (24%)
      patients (group T) required thoracotomy and decortication of an empyema thoracis.
      Only seven (17%) patients were operated upon within 7 days of presentation, and
      10 patients (24%) waited for more than 21 days. The delay from presentation to
      operation was significantly longer in group T (22 days vs. 10 days, P < 0.05,
      Wilcoxon). There were significantly more preoperative pleural interventions in
      patients in group T than in group V (P < 0.05, Wilcoxon). Postoperative stay was
      longer in group T (7 days vs. 3 days, P < 0.05) and there was a significant
      overall correlation between preoperative delay and postoperative stay (r = 0.64).
      CONCLUSION: Delayed referral for pneumothorax surgery and multiple pleural
      interventions predispose to pleural sepsis and preclude VATS detrimentally
      affecting clinical outcome. Changes in referral practice are advocated.

PMID- 9616521
TI  - An evaluation of the use of concentrators for domiciliary oxygen supply for less
      than 8 h day-1.
AB  - Since their introduction in 1985, oxygen concentrators have only been recommended
      when domiciliary oxygen is used for over 8 h day-1. Subsequent changes in the
      prices of oxygen merit a reappraisal of the prescribing of concentrators and
      cylinders when oxygen is used for less than 8 h day-1. Twenty-six patients in two
      health districts who used oxygen for less than 8 h day-1 completed a crossover
      study in which each group received oxygen from each source for consecutive 3
      month periods. The patients were visited at home before and during the study, and
      on each visit they completed a questionnaire asking about their use of oxygen,
      how acceptable they found the two sources and about several dimensions of their
      quality of life. The theoretical minimum cost of cylinder supply, the actual cost
      of cylinder supply and the average concentrator costs were assessed. The patients
      found the concentrators to be more acceptable, more useful and less obtrusive
      than cylinders. They used more oxygen in more rooms of the home during treatment
      with concentrators, and there were improvements in the quality-of-life
      measurements. The costing information showed that, both in theory and in
      practice, oxygen concentrators are cheaper than cylinders when oxygen is used for
      more than about 1.4 h day-1. These results suggest that the provisions for the
      supply of domiciliary oxygen should be reviewed and that concentrators should be
      recommended for patients who use more than around 1.4 h day-1.

PMID- 9616522
TI  - The efficacy and safety of salmeterol compared to theophylline: meta-analysis of
      nine controlled studies.
AB  - The aim of this study was to compare the efficacy and safety of salmeterol vs
      theophylline in asthma management using meta-analysis of clinical trials. Nine
      clinical studies, containing a total of 1330 patients, met meta-analysis
      inclusion criteria: randomized, controlled study, minimum 2-week treatment
      duration with either salmeterol or theophylline. The main outcome measurements
      were morning and evening peak expiratory flow rate (PEFR), morning and evening
      symptom scores, use of salbutamol as rescue medication, and withdrawal from
      treatment for any cause. During the second week of treatment, salmeterol patients
      had a 10 l min-1 greater increase in mean morning PEFR from baseline than
      theophylline patients (P < 0.001). Similarly, in the second week, the increase in
      mean evening PEFR from baseline observed with salmeterol was significantly
      greater (P < 0.01) than that observed with theophylline. Salmeterol also produced
      a significantly greater increase in mean morning and evening PEFR than
      theophylline at weeks 3 and 4. Patients receiving salmeterol were free from
      daytime symptoms for a mean of 51% of days in the second week compared to 39% for
      theophylline patients (P < 0.001). Salmeterol patients experienced a mean of 63%
      symptom-free nights compared to 52% for theophylline patients (P < 0.001). Rescue
      medication with salbutamol was not required on 49% of days for salmeterol
      patients and 34% of days for theophylline patients. All results were maintained
      in the third and fourth weeks of treatment. Withdrawal and incidence of adverse
      events leading to withdrawal were significantly less frequent in patients
      receiving salmeterol (P < 0.001). Thus, this meta-analysis suggests that
      salmeterol has a superior safety and efficacy profile to theophylline in the
      management of symptoms of chronic asthma.

PMID- 9616523
TI  - Implementing the British Thoracic Society's guidelines: the effect of a nurse-run
      asthma clinic on prescribed treatment in an English general practice.
AB  - The advent of computer-based prescribing in general practice has made it possible
      to study a patient's drug use in detail. This study compared the use of inhaled
      therapy in 100 patients with chronic disease by examining every prescription
      issued during the year before and the year after initial consultation at a nurse
      run asthma clinic. The majority were poorly controlled in that 79% scored high on
      the Jones Morbidity Index at their first visit. The number of patients on inhaled
      corticosteroid and salmeterol xinafoate rose from 87 to 100% and 6 to 28%,
      respectively, while those instructed to take their beta-agonist 'when required'
      as opposed to a regular dose rose from 26 to 82%. The daily median intake of
      short-acting beta-agonist fell from 5.0 to 3.8 doses (P < 0.0001). In the 87
      patients on inhaled corticosteroid throughout, the mean daily dose increased from
      532.1 to 793.1 micrograms (P < 0.0001), and compliance (defined as the total dose
      issued in 1 year expressed as a percentage of that recommended) increased from
      61.5 to 69.3% (P = < 0.05). Attendance at a nurse-run asthma clinic was
      associated with a number of significant alterations in inhaled therapy. These
      changes conformed to the British Thoracic Society's guidelines.

PMID- 9616524
TI  - Do Nottingham Health Profile scores change over time in cystic fibrosis?
AB  - We have previously shown that the Nottingham Health Profile (NHP) shows good
      correlation with physiological scores in an adult cystic fibrosis (CF) population
      when assessing health status (HS). The aim of this study was to determine whether
      the NHP can detect change in HS over time. Patients attending an adult CF clinic
      were studied at the time of their 'annual review' appointment. HS was assessed by
      the NHP and an 'in house' CF-specific score was used. FEV1% predicted, FVC%
      predicted, FEV1/FVC ratio, and body mass index (BMI) were calculated. The
      patients were then studied at subsequent annual review appointments. Change over
      time was calculated for each parameter and the relationship between change in HS
      and change in physiological parameters was examined using Spearman's rank
      correlation. Initial (t1), NHP scores were obtained from 204 patients, median age
      26 years (range 16-56 years). Follow-up scores were obtained from 152 patients
      (t2). The mean rate of change in FEV1 was -8.6 (261) ml yr-1 or -0.2 (6.9)%
      predicted yr-1. The only dimension of the NHP which showed a significant change
      over time was emotion, which showed a small improvement in score (score at t1 =
      11.3, score at t2 = 8.1, P = 0.02). There was a significant deterioration in the
      CF-specific total score (t1 = 4.4, t2 = 4.7, P = 0.008). There were no
      significant correlations between change in physiology and change in NHP scores.
      There was no overall difference in change in NHP scores between the patients
      whose FEV1 declined at > 4% predicted yr-1 and those who did not. In conclusion,
      although the NHP correlates well with one-off physiological parameters, there is
      poor correlation between change in NHP scores and change in physiological
      parameters over time.

PMID- 9616525
TI  - Measurement of hepatocyte growth factor in serum and bronchoalveolar lavage fluid
      in patients with pulmonary fibrosis.
AB  - The present study evaluated the clinical significance of hepatocyte growth factor
      (HGF) in patients with pulmonary fibrosis. Twenty-one patients with a diagnosis
      of pulmonary fibrosis [14 with idiopathic pulmonary fibrosis (IPF) and seven with
      pulmonary fibrosis associated with a collagen vascular disorder (PF-CVD]) and 21
      normal subjects as control were studied. HGF levels in sera of patients with
      pulmonary fibrosis (0.34 +/- 0.02 ng ml-1) were elevated significantly as
      compared with normal subjects (0.21 +/- 0.01 ng ml-1) (P < 0.0001). HGF/albumin
      levels in broncho-alveolar lavage fluid (BALF) of patients with pulmonary
      fibrosis (72 +/- 17 ng g-1 albumin) were also significantly elevated as compared
      with normal subjects (under the detection limit) (P < 0.01). HGF levels in sera
      correlated significantly with elastase levels in sera and C-reactive protein, and
      correlated negatively with PaO2. HGF levels in sera were significantly higher in
      smokers with pulmonary fibrosis (0.42 +/- 0.03 ng ml-1) as compared with non
      smokers with pulmonary fibrosis (0.29 +/- 0.03 ng ml-1) (P < 0.005). HGF/albumin
      levels in BALF correlated significantly with elastase/albumin levels in BALF,
      lactate dehydrogenase/albumin in BALF, Immunoglobulin A/albumin in BALF, total
      cell count/albumin in BALF, total number of alveolar macrophage/albumin in BALF,
      total number of neutrophil/albumin in BALF, CEA/albumin in BALF, CA19-9/albumin
      in BALF, and SCC/albumin in BALF. These results suggest that following lung
      injury, HGF may be a mediator involved in the repair which leads to pulmonary
      fibrosis.

PMID- 9616526
TI  - The effect of oral corticosteroids on bronchodilator responses in COPD.
AB  - There have been suggestions that corticosteroid treatment might improve
      bronchodilator responses in chronic obstructive pulmonary disease (COPD). We have
      studied bronchodilator responses to salbutamol and to oxitropium bromide in 20
      patients with stable moderate to severe COPD. Dose responses to the two
      bronchodilators were tested before and after 3 week courses of placebo and 30 mg
      prednisolone. Thirteen patients were taking inhaled corticosteroids. There were
      no significant changes in numbers of responses or maximum bronchodilator effects
      from either bronchodilator, although there was a trend towards higher maximum
      levels after 3 weeks of prednisolone. Spirometry measured at home each morning
      before and after oxitropium bromide showed no difference between prednisolone and
      placebo periods. This study provides no evidence for a significant effect on
      bronchodilator responses to beta-agonists or anticholinergic agents from 3 weeks
      of oral prednisolone in moderately severe COPD.

PMID- 9616527
TI  - Are symptoms of obstructive sleep apnoea syndrome related to bronchitic symptoms
      or lung function impairment? Report from the Obstructive Lung Disease in Northern
      Sweden Study.
AB  - To investigate whether the high prevalence of symptoms related to obstructive
      sleep apnoea syndrome (OSAS) in a bronchitic cohort is correlated with the
      bronchitic symptoms or lung function impairment we examined two cohorts with
      bronchitic symptoms (n = 357 and 82) and a reference group who had reported no
      respiratory symptoms in a previous survey in 1986 (n = 140). The study was a part
      of the Obstructive Lung Disease in Northern Sweden Study and included clinical
      examination and lung function tests. Although lung function measured as FEV1
      percentage predicted was correlated with bronchitic symptoms we found that
      bronchitic symptoms and body mass index but not lung function impairment were
      correlated with symptoms related to obstructive sleep apnoea. According to our
      findings it was the various bronchitic symptoms such as longstanding cough,
      wheezing, sputum production and chronic productive cough that were correlated
      with OSAS symptoms. This might be due to increased upper airway swelling or
      increased upper airway resistance, and lung function impairment does not seem to
      be responsible for the high prevalence of symptoms related to obstructive sleep
      apnoea in this bronchitic cohort.

PMID- 9616528
TI  - Improving communication between hospital and primary care increases follow-up
      rates for asthmatic patients following casualty attendance.
AB  - Despite adequate access to primary care facilities, there is a group of patients
      who habitually present to hospital accident and emergency (A&E) departments when
      their asthma deteriorates. In Nottingham 50% of these patients are discharged
      from the A&E department without admission to hospital and are advised to inform
      and see their general practitioner (GP), but many fail to do so. We instituted a
      system of identifying all patients seen and discharged from our A&E department
      with asthma and informing their GPs and practice nurses within one working day of
      the event by fax. To determine whether any action had been taken following
      receipt of our fax, we contacted each general practice 1 month after the A&E
      attendance in 100 consecutive cases. Full data were available for 66 patients.
      Our faxes increased the notification of A&E attendances to GPs from 47 to 89%.
      This resulted in an increase in the number of follow-up appointments initiated by
      the practice, from 15 to 31. However, 29% of patients were not asked to attend
      for follow-up, in spite of the practice being aware of a recent A&E visit.
      Improving communication between hospital and general practice increases the rate
      of follow-up by GPs for patients with asthma who have been discharged from A&E.
      This has the potential to improve asthma management for this group of patients.

PMID- 9616529
TI  - A comparison of regular salmeterol vs 'as required' salbutamol therapy in
      asthmatic children.
AB  - In a multicentre, double-blind, randomized, parallel study, 426 asthmatic
      children aged 5-15 years old received salmeterol 50 micrograms b.i.d. or placebo
      b.i.d. via the Diskhaler. All patients had access to inhaled salbutamol to be
      used on an 'as required' (p.r.n.) basis for symptomatic relief. The study design
      comprised a 2-week baseline, a 12-month treatment period incorporating a 2-week
      'off treatment' after 6 months, and a 2-week follow-up period at the end of the
      trial. At the end of 12 months of treatment with salmeterol, the adjusted change
      from baseline for morning and evening peak expiratory flow rate (PEF) was 56 and
      47 l min-1, respectively, and this was significantly greater than placebo (P <
      0.01; P < 0.05). Exacerbation rates did not differ between groups and results
      were not dependent upon concurrent inhaled steroid use. Neither treatment caused
      a change of > or = 1 doubling dose in PC20/PD20 either during or on stopping
      treatment. Treatment with regular salmeterol 50 micrograms b.i.d. over a 12-month
      treatment period provides a significant, rapid and well-maintained improvement in
      lung function without increasing bronchial reactivity or asthma exacerbation
      rates compared to p.r.n. salbutamol.

PMID- 9616530
TI  - One-year economic evaluation of intensive vs conventional patient education and
      supervision for self-management of new asthmatic patients.
AB  - The purpose was to compare the short-term cost-effectiveness of intensive vs
      conventional education and supervision for the self-management of mild asthmatic
      patients. Consecutive newly diagnosed asthmatic patients (n = 162) were
      randomized into an intervention group (IG) and a control group (CG) with 1 yr of
      treatment and follow-up. Intensive education was given to 77 patients at visits
      every third month in the outpatient clinic. Eighty CG patients received
      conventional education and advice at the baseline visit only. All patients
      received similar inhaled anti-inflammatory treatment. At baseline and at 12
      months standard clinical lung functions and health-related quality of life
      (HRQOL) were measured, the latter by the disease-specific St George's Respiratory
      Questionnaire and the generic 15D. Furthermore, the use of extra health care
      services, medication and sickness days were recorded. The IG experienced a
      significant improvement in all clinical and HRQOL outcome variables. The same
      applied to the CG except spirometric values. The groups differed significantly
      only in terms of FEV1 (P < 0.05) in favour of the IG. There was a significant
      difference between the groups in extra costs. The mean cost was FIM 2351 per
      patient (294 Pounds sterling) in the CG and FIM 2757 per patient (345 Pounds) in
      the IG, of which the intervention cost was FIM 1978 per patient (247 Pounds). In
      1 yr follow-up the intensive education programme did not prove to be cost
      effective but was dominated by the conventional one regardless of what
      effectiveness measure was used. Also, a purely monetary cost-benefit calculation
      showed that the intervention resulted in a negative net benefit (loss) of FIM 406
      per patient (51 Pounds). A longer follow-up may be needed before definitive
      conclusions about the cost-effectiveness of this kind of intervention can be
      drawn.

PMID- 9616531
TI  - Cold air inhalation and exercise-induced bronchoconstriction in relationship to
      metacholine bronchial responsiveness: different patterns in asthmatic children
      and children with other chronic lung diseases.
AB  - Cold air inhalation and exercise-induced bronchoconstriction (EIB) have both been
      used as measures of bronchial responsiveness. Both stimuli are often combined in
      the Nordic climate. The main objective of the present study was to investigate
      the climatic influence of cold temperatures upon exercise-induced asthma. The
      secondary aims were: (a) to assess metacholine bronchial hyper-responsiveness and
      EIB in children with bronchial asthma (n = 32; mean age 10.8 years) compared to
      children with other chronic lung diseases (CLD) (n = 26, mean age 10.1 years);
      and (b) to assess the influence of cold air inhalation upon EIB in the two groups
      of children. Methods used were: (a) the metacholine concentration causing a
      reduction in FEV1 of 20% (PC20-M), (b) maximum FEV1 fall (delta FEV1) after
      submaximal treadmill run (EIB test); and (c) delta FEV1 after submaximal
      treadmill run while inhaling cold (-20 degrees C) dry air (CA-EIB test).
      Geometric mean PC20-M did not differ significantly between the asthma children
      (1.28 mg ml-1) and the CLD children (2.90 mg ml-1). In the asthma children, mean
      delta FEV1 after EIB test was 12.8% vs 21.8% after adding cold air (P < 0.0001),
      compared to 5.2 and 7.4%, respectively (P = 0.03), in the CLD group. Maximum
      sensitivity and specificity for the EIB test were 69.8% at a fall in FEV1 of
      6.8%; for the CA-EIB test, 72% at a fall in FEV1 of 10.2%; and for metacholine
      provocation, 56% at a PC20-M of 1.5 mg ml-1. In conclusion, children with
      bronchial asthma are substantially more sensitive to cold air than children with
      CLD, and EIB is markedly increased by cold air inhalation in asthmatic children,
      maintaining the specificity of the EIB test and increasing the sensitivity. The
      low sensitivity of the EIB test is probably influenced by the use of inhaled
      steroids. Metacholine inhalation test has less specificity and sensitivity in
      discriminating asthma from other chronic lung diseases.

PMID- 9616532
TI  - Asthma, type-1 allergy and related conditions in 7- and 8-year-old children in
      northern Sweden: prevalence rates and risk factor pattern.
AB  - As a first step in an intervention study of asthma and allergic diseases among
      school children, a cross-sectional study was performed during Winter 1996 in
      three towns (Kiruna, Lulea and Pitea) in the northernmost province of Sweden,
      Norrbotten. The cross-sectional study aimed to measure the prevalence of asthma,
      type-1 allergy and allergic diseases in order to make it possible to measure the
      incidence of the diseases, conditions and symptoms related to the diseases.
      Another aim was to perform a screening for possible risk factors. All children
      enrolled in the first and second classes at school, 7 and 8 years old, were
      invited to take part in this study. The ISAAC questionnaire with added questions
      about symptoms, morbidity, heredity and environment was distributed by the
      schools to the parents. The response rate was 97%, and 3431 completed
      questionnaires were returned. The children in two of the municipalities were also
      invited to skin test, and 2149 (88%) were tested with 10 common airborne
      allergens. The results showed that 7% of the children were currently using or had
      used asthma medicines during the last 12 months. Six percent had asthma diagnosed
      by a physician, and 4% were using inhaled corticosteroids. The prevalence of
      wheezing during the last 12 months was 12%, rhinitis without colds 14%, and
      eczema 27%, while 21% had a positive skin test. The respiratory symptoms and
      conditions were significantly greater in boys and, further, they were most
      prevalent in Kiruna in the very north, though not significantly. Type-1 allergy
      and asthma had different risk factor patterns. The main risk factors for asthma
      were a family history of asthma (OR = 3.2) followed by past or present house
      dampness (OR = 1.9), male sex (OR = 1.7) and a smoking mother (OR = 1.6). In
      Kiruna, when none of these three risk factors were present, none of the children
      had asthma, but when all three were present, 38% of these children were using
      asthma medicines.

PMID- 9616533
TI  - Safety and efficacy of a high cumulative dose of salbutamol inhaled via
      Turbuhaler or via a pressurized metered-dose inhaler in patients with asthma.
AB  - An open, crossover and randomized study was carried out to compare the safety and
      efficacy of salbutamol inhaled using the dry-powder inhaler Turbuhaler, and using
      a pressurized metered-dose inhaler (pMDI). Twelve patients with moderate to
      severe asthma, aged 47-68 years, were included in the study. On two separate
      days, patients received a total dose of 1600 micrograms of salbutamol
      administered in a cumulative dose fashion: 100, 100, 200, 400 and 800 micrograms
      at 3-min intervals. Salbutamol inhaled via Turbuhaler caused a larger decrease in
      serum potassium concentration than did salbutamol inhaled via pMDI. The estimated
      relative dose potency of the hypokalaemic effect of salbutamol Turbuhaler vs
      salbutamol pMDI was 2.0 with a 95% confidence interval of 1.3-3.6. Turbuhaler
      caused a small (but statistically significantly greater than with pMDI) increase
      in heart rate, QTc interval and tremor. Blood pressure was unaffected by the
      treatments. No adverse events of clinical relevance were reported. The estimated
      relative dose potency of the bronchodilating effect (FEV1) of salbutamol
      Turbuhaler vs salbutamol pMDI was 3.0 with a 95% confidence interval of 1.8-5.8.
      In conclusion, salbutamol inhaled via Turbuhaler was more potent and seemed to
      have a better therapeutic ratio than salbutamol inhaled via pMDI. Both treatments
      were equally well tolerated.

PMID- 9616534
TI  - Haemodynamic response during initiation of non-invasive positive pressure
      ventilation in COPD patients with acute ventilatory failure.
AB  - The aim of this study was to check non-invasively the acute haemodynamic effects
      of non-invasive positive pressure ventilation (NPPV) initiation in patients with
      chronic obstructive pulmonary disease (COPD) and acute ventilatory failure (AVF).
      Nineteen consecutive COPD patients with AVF were evaluated clinically and
      echocardiographically during spontaneous breathing with O2 supplementation and
      during NPPV plus O2. NPPV was administered with a scheduled inspiratory pressure
      of 15 cmH2O and an expiratory pressure of 4 cmH2O, via facial mask. Arterial
      blood gas improved significantly (pH and PaCO2; P < 0.001) during NPPV
      administration in all patients; none had hypotension or acute arrhythmia. Doppler
      echocardiographic evaluation was feasible in most of the patients (16/18). With
      reference to baseline values, no significant changes in pulmonary artery
      pressures and cardiac output (CO) were observed by Doppler echocardiography in
      most patients. Only four patients (21%) showed a significant reduction (> 15%) of
      CO during NPPV. No correlation was found between decreased CO and baseline data,
      but three patients showing CO reduction had poor tolerance to mask ventilation
      and did not improve respiratory rate during NPPV. It was concluded that the
      initiation of NPPV by facial mask does not alter haemodynamics acutely in most
      COPD patients with AVF, but individual patients may experience reduction in CO in
      spite of adequate oxygen saturation levels. This suggests that caution should be
      used when applying pre-determined and fixed pressures during NPPV. Monitoring
      haemodynamics by Doppler echocardiography may be useful for early detection of
      haemodynamic alterations due to NPPV application in patients with AVF.

PMID- 9616535
TI  - Interleukin-8 expression in bronchoalveolar lavage cells in the evaluation of
      alveolitis in idiopathic pulmonary fibrosis.
AB  - Interleukin-8 (IL-8) is a neutrophilic chemotactic factor which may have a
      prominent role in the attraction of neutrophils to the lung in idiopathic
      pulmonary fibrosis (IPF). The objective of this study was to investigate the
      usefulness of IL-8 expression in bronchoalveolar lavage (BAL) cells in the
      evaluation of alveolitis in IPF. We analysed the BAL cell expression of IL-8 by
      immunocytochemistry in 19 patients with IPF (six smokers, three ex-smokers and
      ten non-smokers) and in a control group composed of 14 individuals (six smokers,
      eight non-smokers). In IPF, BAL was performed on both the pulmonary lobe with the
      most extensive involvement and the one less extensively involved on high
      resolution computed tomography (HRCT) scans. The percentages and absolute numbers
      of BAL IL-8+ macrophages from lobes with the most extensive HRCT scan involvement
      (36 +/- 6% and (6 +/- 2 x 10(4) ml-1) (SE) and from those less extensively
      involved [26% +/- 4% and (6 +/- 1) x 10(4) ml-1] were significantly higher with
      respect to both those from healthy smokers [17% +/- 6% and (7 +/- 4) x 10(4) ml
      1] and those from non-smokers [2% +/- 1% and (1 +/- 0.3) x 10(4) ml-1] (P = 0.005
      and P = 0.001, respectively), without differences between the two lobes. In
      contrast, both the proportions and the absolute numbers of BAL neutrophils in IPF
      were significantly higher in lobes with the most extensively involved HRCT scan
      in comparison with lobes with the least extensive involvement [13% +/- 3%, (3 +/-
      1) x 10(4) ml-1 vs. 8% +/- 2%, (1 +/- 0.3) x 10(4) ml-1, P = 0.05]. Moreover, the
      numbers of BAL neutrophils, but not those of IL-8+ macrophages, correlated with
      the extent of total pulmonary HRCT scan abnormalities in the most involved lobe
      (r = 0.64, P = 0.04). A correlation between neutrophils and IL-8+ cells was not
      observed. The results of this study suggest that, in IPF, BAL neutrophilia offers
      a better description of the disease inflammatory process than the expression of
      IL-8 in BAL cells.

PMID- 9616536
TI  - Time trends and seasonal variation in acute childhood asthma in tropical
      Singapore.

PMID- 9616537
TI  - Fluticasone propionate: an audit of outcomes and cost-effectiveness in primary
      care.

PMID- 9616538
TI  - A comparison of bronchodilating effects of salmeterol and oxitropium bromide in
      stable chronic obstructive pulmonary disease.
AB  - Anti-cholinergic agents are generally regarded as the bronchodilator therapy of
      first choice in the treatment of stable chronic obstructive pulmonary disease
      (COPD), considering that they may be more effective than in inhaled beta 2
      agonist. However, results of the authors' recent studies conflict to some extent
      with this suggestion because they demonstrate that this is true only for short
      acting beta 2-agonists but not for long-acting beta 2-agonists. Oxitropium
      bromide is an anti-cholinergic drug that has been shown to produce a similar
      degree of bronchodilation to that obtained with ipratropium bromide, but with a
      longer-lasting effect. In the present study, the time course of inhaled
      oxitropium bromide bronchodilation in comparison to that of inhaled salmeterol in
      a group of patients with partially reversible COPD was evaluated. Twelve male
      patients with moderate to severe COPD participated in the study. The study had a
      single-bind, cross-over, randomized design. The bronchodilator activity of 50
      micrograms salmeterol hydroxynaphthoate, 200 and 400 micrograms oxitropium
      bromide and placebo, which were all inhaled from a metered-dose inhaler, was
      investigated on several non-consecutive days. The highest FVC and FEV1, obtained
      from one or the other of the reproducible curves, were kept for analysis.
      Measurements were performed at the following times: immediately before inhalation
      of treatment, and at 15, 30, 60, 120, 180, 240, 300, 360, 480, 600 and 720 min
      after inhalation of the individual treatment. Salmeterol tended to have a delayed
      time to peak effect, but had a longer duration of effect than oxitropium. The
      response to salmeterol exceeded the response to 200 micrograms oxitropium for 12
      h, but its responses were significantly (P < 0.05) greater than those to 200
      micrograms oxitropium from 10 to 12 h. From 3 to 12 h, salmeterol also surpassed
      400 micrograms oxitropium but differences were not significant (P < 0.05). The
      mean FEV1 area under the curve was significantly (P < 0.05) larger after
      salmeterol when compared to 200 micrograms oxitropium bromide, but there was no
      significant difference (P < 0.05) between salmeterol and 400 micrograms
      oxitropium bromide. No significant changes in pulse rate, blood pressure or
      electrocardiograms were found among the four groups as compared with placebo
      group. These findings confirm and extend what has been demonstrated by the
      authors' previous studies, and show that salmeterol compares conveniently with
      anti-cholinergic drugs in terms of effects on lung function at clinically
      recommended doses.

PMID- 9616539
TI  - Apical pleural mass developing following talc pleurodesis.

PMID- 9616540
TI  - Rhabdomyolysis and bacterial pneumonia.

PMID- 9616541
TI  - A new approach to the treatment of Xanthomonas maltophilia respiratory infection
      in a patient with cystic fibrosis.

PMID- 9616542
TI  - Nurses must not adopt medical roles piecemeal.

PMID- 9616543
TI  - Nurses must improve their record keeping skills.

PMID- 9616544
TI  - Nutritional supplements and tube feeds: what is available?
AB  - A wide range of specialized nutritional feeding products are now available. One
      condition for which nutritional feeding products are commonly prescribed is
      disease-related malnutrition. Nutritional support for poorly nourished clients
      consists of more than simply prescribing a specialized product. Key nutrition
      messages need to be applied to individual situations to promote optimal
      nutritional intake. However, in many situations clients are unable to meet their
      nutritional requirements by food alone and nutritional supplement products are
      then extremely useful. The nutritional status of all those receiving nutritional
      support should be monitored regularly; as the client's nutritional status
      improves, his/her intake of these products may need to be reduced or stopped. If
      clients are unable to maintain or improve their nutritional status despite the
      use of nutritional supplements, additional help from an alternative feeding
      product may be required.

PMID- 9616545
TI  - Palliative care: promoting the concept of a healthy death.
AB  - The thought of having a life-limiting disease and/or dying can be a fearful
      prospect. However, a positive approach to palliative care can help the individual
      and his/her family to approach the last stages of life with hope and, for some
      people, fulfilment. This article explores a positive health promotion approach to
      palliative care. This approach is underpinned by the principles of the Ottawa
      Charter (World Health Organization (WHO), 1986) which specifies advocacy,
      enabling, and mediacy as the three central elements of health promotion. The
      nurse as patient advocate can help to ensure that the wishes of the dying person
      are met. The principles of enabling can help the dying person and his/her family
      to remain involved in key decisions while mediacy between caregivers can ensure
      that death occurs in the most appropriate setting for the individual. Through
      this approach nurses can play a pivotal role in the multidisciplinary team both
      as agents of change and as providers of care and support to the dying person and
      his/her family.

PMID- 9616546
TI  - Cancer of the prostate. 3: Men's healthcare needs.
AB  - This article, the third in a three-part series, addresses the complex issues
      surrounding screening for prostate cancer. The purpose of screening in health
      care is discussed and the advantages and disadvantages of the various screening
      tests for the early detection of prostate cancer are outlined. The use of one
      specific technique to screen men for prostate cancer is questioned. It is
      suggested that several techniques should be used to assess risk in detail.
      Employing only one technique, for example prostate specific antigen, may result
      in men undergoing unnecessary surgery or inappropriate treatment. Nurses have a
      professional duty to ensure that they are aware of the advantages and
      disadvantages with respect to screening men for cancer of the prostate. Patients'
      must be in possession of the facts before they make important decisions about
      their health. In order to reduce harm the nurse can become the patient's advocate
      and act in such a way as to safeguard and promote the patient's interests.

PMID- 9616547
TI  - Specialist practice and the professional project for nursing.
AB  - This article examines the implications of the UKCC's (1994) decision to determine
      a sphere of practice for specialist practitioners. It coincides with the move
      towards professional status within nursing. It is argued that a specialization
      strategy for nursing has obvious advantages for those who wish nursing to be
      successful in its professionalization. However, unless managers use long-term
      planning the potential of specialist nursing practice may not be realized. It is
      suggested that the professionalization of nursing (professional project) is
      strongly linked to the fact that nursing remains a predominately female
      occupation (Witz, 1992), and initiatives, such as specialization, should be
      viewed from this standpoint. Clinical leadership is crucial to the success of
      specialism within nursing over the next few years. Opportunities need to be taken
      to reappraise specialist practitioner roles, and allow innovation to occur.
      Financial and educational support needs to be available and responsive; the
      clearer the message is regarding a clinical career structure for nursing, the
      more likely the 'professional project' is to succeed.

PMID- 9616548
TI  - Nursing's knowledge base: does it have to be unique?
AB  - An International Seminar held at the University College of Health Sciences,
      Jonkoping, Sweden, in May 1996, was the stimulus for this article. The purpose of
      the seminar was to consider the contribution that nursing theory has made to the
      development of the profession and to identify ways in which this contribution
      could be enhanced. This article briefly traces the emergence of nursing theory
      and argues that despite its relatively short history, theory has failed fully to
      inform practice and is increasingly seen as irrelevant. It is suggested that two
      trends--the abstract and esoteric nature of much nursing theory and the desire to
      create a unique' body of nursing knowledge--must be countered before theory can
      establish its value. It is argued that these are manifestations of professional
      and academic insecurity which nursing must overcome before it can reach maturity.

PMID- 9616549
TI  - An alternative training approach to clinical supervision: 1.
AB  - This article, the first of two-parts, introduces a new series on clinical
      supervision. It focuses on the issues of training in clinical supervision. The
      practice of clinical supervision is considered by the Chief Nursing Officer of
      the Department of Health to be fundamental to safeguarding standards, the
      development of expertise and the delivery of quality care. Clinical supervision
      allegedly brings significant benefits to clients and clinicians, and recent
      research has produced both quantitative and qualitative evidence to support this
      argument. Many trusts have already made attempts to introduce widespread
      implementation of clinical supervision and most developments are concerned with
      equipping clinicians to be supervisors not supervisees. This presents several
      logistical and financial problems, and currently neither the infrastructure nor
      the culture exist in nursing to facilitate its widespread and effective uptake.
      The authors argue that an alternative method of tackling this problem would be to
      train nurses to become supervisees not supervisors. Supervisee training could
      commence following the first year of the common foundation programme component of
      diploma and undergraduate nurse education.

PMID- 9616550
TI  - Metrotop: a topical antimicrobial agent for malodorous wounds.
AB  - The eradication of pungent wound odour is one of the most challenging problems
      for health professionals involved in wound management. The presence of malodour
      can cause immeasurable distress for the patient and his/her family, making many
      sufferers' lives one of self-imposed exile. Clinical research using topical
      metronidazole over the past 20 years clearly indicates that metronidazole is
      effective against the anaerobic bacteria that cause these foul and distressing
      odours. Seton Healthcare produces a commercial preparation called Metrotop--a
      topical metronidazole gel which is available on prescription.

PMID- 9616551
TI  - How to improve the morale of nursing students.

PMID- 9616553
TI  - Staffing to meet patient care needs.

PMID- 9616554
TI  - The use of unregulated workers in Toronto hospitals.

PMID- 9616555
TI  - Patient requirements for nursing care: the development of an instrument.
AB  - The determination of nursing staff mix is a challenge for many health care
      agencies. Staff mix decisions have historically been based on workload
      measurement information, the type of patient care unit and on a subjective or
      intuitive basis. Weighted task lists (workload measurement systems) do not
      comprehensively consider the skill and knowledge level required to meet patient
      care needs. This project describes the development of an instrument that
      considers patient's nursing care needs as a determinant of nursing staff mix.
      Recommendations for the use of the tool are identified.

PMID- 9616556
TI  - A computer-generated measure of nursing workload for the emergency department
      based on discharge diagnosis.
AB  - A computer-based system which automatically generates nursing workload figures
      for the Emergency Department is described. This system uses measures derived from
      the GRASPR system, linked to the discharge diagnosis, to generate total workload
      figures, obviating the need for data collection or input beyond the initial
      implementation.

PMID- 9616557
TI  - Nurse manager selection process (Part 1). Survey of selection process (Part 2).
AB  - The Queen Elizabeth II Health Sciences Centre developed as a result of the merger
      of the five adult hospitals in Halifax, Nova Scotia. The merge involved 7000
      staff members, 2700 of whom were nursing staff. Although mergers are becoming
      relatively common amongst health care organizations, there is a paucity of
      information in the literature to describe such an enormous human resource effort.
      This two-part article describes the hiring process for the selection and
      placement of 52 nurse managers over a concentrated time period of six weeks.
      Issues identified and resolved included: unionized and non unionized head nurses,
      the role of nurse managers, varying educational preparations, the time frame and
      organization of the process itself, options for unsuccessful incumbents, and
      multi unit and multi site management. The second part of the article reports on
      the results of a survey which was carried out to obtain feedback from the
      applicants and the interview panel members. The survey was conducted within eight
      weeks of the conclusion of the hiring process. Overall the process was deemed
      successful, albeit stressful. Some of the problems encountered are discussed.

PMID- 9616558
TI  - Cancer-related fatigue: clinical practice issues.
AB  - The purpose of this paper is to review current nursing literature and practice in
      cancer-related fatigue and to provide a suggested plan of treatment. Cancer
      related fatigue is one of the most common and challenging symptom-management
      problems. The successful treatment of fatigue depends on the clinician's
      understanding of the symptom's continuum within the cancer experience, its
      etiologies, assessment strategies, and research-based interventions. Clinical
      outcomes are measured by the patient's ability to balance energy expenditure and
      restoration. By applying this knowledge to clinical practice, oncology nurses can
      have a profound impact on the patient's quality of life.

PMID- 9616559
TI  - Current issues in the surgical treatment of early stage breast cancer.
AB  - Surgery remains the primary treatment for early stage breast cancer. Modified
      radical mastectomy and lumpectomy with axillary dissection continue to be the two
      procedures most commonly performed. Changes in the healthcare system and advances
      in medical research in cancer treatment affect the nursing care of these
      patients. The introduction of the sentinel node biopsy may change certain aspects
      of surgical treatment, as some patients may not require an axillary dissection.
      The challenge for nurses is to provide quality care and maintain established
      standards for patients with breast cancer as their hospitalizations are shortened
      to same day or overnight stays. The purpose of this article is to review the
      standard surgical treatments and related nursing care and discuss the impact of
      the sentinel node biopsy and the impact of changes in the length of hospital stay
      on the care of women with breast cancer.

PMID- 9616560
TI  - Ovarian cancer surgery: a clinical pathway.
AB  - Clinical pathways are useful tools in providing quality care while decreasing the
      cost of that care. Pathways help to facilitate managed care, identify patient and
      family educational needs, encourage multidisciplinary communication, and expedite
      patient discharge. This article discusses a clinical pathway for ovarian cancer
      surgery.

PMID- 9616561
TI  - Individual professional liability insurance: who needs it?

PMID- 9616562
TI  - Hypercalcemia.

PMID- 9616564
TI  - Comparison of teaching behaviors used by nurse practitioner and physician faculty
      teaching primary care.

PMID- 9616563
TI  - Satisfaction with practice in a rural state: perceptions of nurse practitioners
      and nurse midwives.
AB  - Data from nurse practitioners and certified nurse midwives are used to explore
      contributions to primary care in a rural state and how regulatory restrictiveness
      and other factors affect satisfaction with practice (N = 151). Satisfaction is
      high, especially with home communities and professional aspects of work,
      including collaboration with physicians. However, many feel limited by
      regulations and are less satisfied, especially those with a master's degree and
      those in organizational versus office practice sites. Reducing restrictive
      regulations, reevaluating practice structures, and providing for full scope of
      practice and other incentives consistent with rising educational levels can
      increase access to care.

PMID- 9616565
TI  - Pharmacology resources on the Internet.

PMID- 9616567
TI  - Mentoring and self-efficacy for advanced nursing practice: a philosophical
      approach for nurse practitioner preceptors.
AB  - Nurse practitioners (NPs), frequently called upon by graduate schools of nursing
      to be preceptors for NP students, are asked to play an active role in the
      socialization of these students as capable primary care providers. Much is
      expected of the preceptor in the typical short-term clinical preceptorship with
      little guidance available to her or him. A mentoring model of clinical education,
      while representing a longer-term commitment for preceptors than usual precepting
      arrangements, may ultimately be a more effective model for student learning and
      more satisfying for the preceptor than currently practiced models. Eastern
      philosophical principles, very much in harmony with valued nursing approaches to
      relationships, can provide a framework for examining mentoring as a strategy for
      promotion of self-efficacy for advanced practice that can be of benefit to both
      the NP preceptor and the NP neophyte.

PMID- 9616566
TI  - Congestive heart failure.
AB  - The differentiation between systolic and diastolic CHF is clinically important
      because it allows one to formulate an appropriate therapeutic regimen. As a rule,
      ACE inhibitors have become a major component in the treatment of systolic heart
      failure; diuretics, digoxin, and other vasodilators are used in conjunction with
      them. Optimal therapy for diastolic heart failure remains to be defined. Further
      research is required for this subset of patients. Numerous other support
      measures, such as counseling, activity, diet, patient knowledge of medications,
      and compliance, all affect the patient's outcome.

PMID- 9616568
TI  - Diabetes mellitus information on the Internet.

PMID- 9616569
TI  - Preparing the next generation: precepting nurse practitioner students.

PMID- 9616570
TI  - GAS disease: what is it and how is it treated?

PMID- 9616571
TI  - Coronary artery disease: a link between hypertension, diabetes mellitus,
      hyperlipidemia, and obesity.

PMID- 9616572
TI  - [Single and group education of children and adolescents with diabetes mellitus in
      the hospital].

PMID- 9616573
TI  - [Diabetes mellitus in pediatric home care].

PMID- 9616574
TI  - [Psychosocial situation and quality of life of children and adolescents with
      diabetes mellitus].

PMID- 9616575
TI  - [Psychosocial care. School for sick children at the Olga Hospital].

PMID- 9616576
TI  - [Sense and nonsense in hygienic measures].

PMID- 9616577
TI  - [Rehabilitation care. A mother-child facility at the Seehospiz "Kaiserin
      Friedrich" in Norderney].

PMID- 9616578
TI  - [Education in pediatric nursing. Practical training from the head nurse's point
      of view].

PMID- 9616579
TI  - [Medicine and social legislation. Legal warnings are often the cause of
      conflict].

PMID- 9616580
TI  - [A model foe practical student training].

PMID- 9616581
TI  - [Education in pediatric nursing. Practical training from the viewpoint of
      Austrian and German students].

PMID- 9616582
TI  - Masters in the art of caring.

PMID- 9616583
TI  - Myths & facts ... about suicide in the elderly.

PMID- 9616585
TI  - Admixing drugs in a syringe.

PMID- 9616586
TI  - Inhaled steroids and oral candidiasis. Help your patient avoid this troubling
      symptom.

PMID- 9616588
TI  - 10 rules for good charting.

PMID- 9616587
TI  - Treating infected wounds.

PMID- 9616589
TI  - Guide to cardiac sites.

PMID- 9616590
TI  - Shaken baby syndrome.

PMID- 9616591
TI  - Abdominal aortic aneurysm.

PMID- 9616592
TI  - Chronic dyspnea. Controlling a perplexing symptom.

PMID- 9616593
TI  - Lesson from Colorado. Beyond blaming individuals.

PMID- 9616594
TI  - Removing a nontunneled central catheter.

PMID- 9616595
TI  - What five regulatory trends mean to you.

PMID- 9616596
TI  - What you'll need to succeed.

PMID- 9616597
TI  - Transdermal patches. What's in a brand name?

PMID- 9616598
TI  - Listen up!

PMID- 9616599
TI  - Just got your pin?

PMID- 9616600
TI  - More charting chuckles.

PMID- 9616602
TI  - A fall in the ED. Did lowered side rails contribute?

PMID- 9616603
TI  - How and when to reference.
AB  - References are not after thoughts, they are critical parts of a quality
      manuscript. The reference section is often one of the first sections of a
      manuscript the editor looks at to see if the author has used the journal's
      guidelines and format. It tells the editor and the reviewer if the author knows
      the field of research, how her or his idea fits, and pays attention to details.
      This experienced reviewer, who has identified some trends in manuscript
      referencing problems, gives advice on how to avoid these problems.

PMID- 9616604
TI  - Mentoring new nurse authors.
AB  - Nurse executives, faculty, and nursing leaders who want to mentor colleagues to
      write can help them by using a step-by-step system with frequent feedback as they
      develop the manuscript. This breaks down the multiple steps to do-able ones and
      gives the new authors help at each juncture, so they avoid the most common
      reasons for rejection. These experienced publishing mentors give an example and
      advice on how nursing leaders can mentor new nurse authors.

PMID- 9616607
TI  - Drug references.

PMID- 9616606
TI  - Publishing research: an ethical question.

PMID- 9616608
TI  - The key to quality nursing care: towards a model of personal and professional
      development.
AB  - Quality of nursing cannot be assessed in terms of performance referenced
      criteria, but only in terms of the personal qualities displayed in the
      performance. The key to improvement in practice may be the improvement of
      emotional and motivational tendencies. In essence, professional development
      implies personal development. Harre makes a distinction between 'powers to do'
      and 'powers to be' (a state of being). The former are the capacities that
      individuals acquire to perform their tasks and roles. Professional development
      therefore involves, first, the acquisition of the capacities necessary for the
      successful completion of a set of professional tasks (the powers to do).
      Secondly, it involves the acquisition of the appropriate emotions and
      motivations, and the theories about human nature and the conduct that underpins
      them (the powers to be). Therefore, these capacities cannot be derived from
      analysis of tasks, since what are defined as tasks in the first place are
      determined by the exercise of such powers. The acquisition of attitudes
      constitutes a source of competent practice. Harre's model of 'personal identity'
      provides a conceptual framework for thinking about the process of the acquisition
      of nursing competence and its relationship to differing views of nursing.
      Considerations relating to different priorities within Harre's model make it
      possible to raise questions about the objectives of competence at different
      stages.

PMID- 9616609
TI  - Self-perception and value system as possible predictors of stress.
AB  - This study was directed towards personality-related, value system and
      sociodemographic variables of nursing students in a situation of change, using a
      longitudinal perspective to measure their improvement in principle-based moral
      judgement (Kohlberg; Rest) as possible predictors of stress. Three subgroups of
      students were included from the commencement of the first three-year academic
      nursing programme in 1993. The students came from the colleges of health at
      Jonkoping, Vaxjo and Kristianstad in the south of Sweden. A principal component
      factor analysis (varimax) was performed using data obtained from the students in
      the spring of 1994 (n = 122) and in the spring of 1996 (n = 112). There were 23
      variables, of which two were sociodemographic, eight represented self-image, six
      were self-values, six were interpersonal values, and one was principle-based
      moral judgement. The analysis of data from students in the first year of a three
      year programme demonstrated eight factors that explained 68.8% of the variance.
      The most important factors were: (1) ascendant decisive disorderly sociability
      and nonpractical mindedness (18.1% of the variance); (2) original vigour person
      related trust (13.3%) of the variance); (3) orderly nonvigour achievement (8.9%
      of the variance) and (4) independent leadership (7.9% of the variance). (The term
      'ascendancy' refers to self-confidence, and 'vigour' denotes responding well to
      challenges and coping with stress.) The analysis in 1996 demonstrated nine
      factors, of which the most important were: (1) ascendant original sociability
      with decisive nonconformist leadership (18.2% of the variance); (2) cautious
      person-related responsibility (12.6% of the variance); (3) orderly nonvariety
      achievement (8.4% of the variance); and (4) nonsupportive benevolent conformity
      (7.2% of the variance). A comparison of the two most prominent factors in 1994
      and 1996 showed the process of change to be stronger for 18.2% and weaker for 30%
      of the variance. Principle-based moral judgement was measured in March 1994 and
      in May 1996, using the Swedish version of the Defining Issues Test and Index P.
      The result was that Index P for the students at Jonkoping changed significantly
      (paired samples t-test) between 1994 and 1996 (p = 0.028), but that for the Vaxjo
      and Kristianstad students did not. The mean of Index P was 44.3% at Vaxjo, which
      was greater than the international average for college students (42.3%) it
      differed significantly in the spring of 1996 (independent samples t-test), but
      not in 1994, from the students at Jonkoping (p = 0.032) and Kristianstad (p =
      0.025). Index P was very heterogeneous for the group of students at Vaxjo, with
      the result that the paired samples t-test reached a value close to significance
      only. The conclusion of this study was that, if self-perception and value system
      are predictors of stress, only one-third of the students had improved their
      ability to cope with stress at the end of the programme. This article contains
      the author's application to the teaching process of reflecting on the structure
      of expectations in professional ethical relationships.

PMID- 9616611
TI  - Racism and its implications in ethical-moral reasoning in nursing practice: a
      tentative approach to a largely unexplored topic.
AB  - Nursing as a profession seems to avoid considering the problem of racism. There
      is, however, a need to address this topic and to evaluate its implications for
      nursing practice. This article attempts to establish a rationale for nursing to
      address racism and introduce it into academic discourse. The results of a small
      scale study by the author are analysed and the implications for ethical-moral
      reasoning in nursing practice are discussed in relation to professional codes of
      conduct developed by nurses' professional organizations in the UK and elsewhere.

PMID- 9616612
TI  - Communication breakdown or ideal speech situation: the problem of nurse advocacy.
AB  - The issue of advocacy has dominated discussion of the ethical dilemmas facing
      nurses. However, despite this, nurses seem to be no further towards a solution of
      how they can be effective advocates for patients without compromising their
      working identity or facing conflicts of loyalty. This article considers some of
      the problems around advocacy and, by the use of critical incidents written by
      nurses involved in a diploma module, attempts to highlight where the problem
      could lie. A communications model is outlined, using a theoretical framework
      taken from the work of Jurgen Habermas, and applied to nursing practice. Finally,
      two examples are given from the research, which illustrate how the model could be
      used, highlighting the problems and pitfalls that still have to be overcome. The
      conclusion is a positive one, in that it suggests that advocacy is possible if
      nurses re-examine their practice in the light of the model proposed.

PMID- 9616610
TI  - An enquiry into a combined approach for nursing ethics.
AB  - A definitive theory for ethical decision making in nursing is still only
      conjecture. The literature confirms that there have been numerous examinations of
      ethical decision making in nursing, with most proposing either the justice or the
      care orientation, or a combination of both. In the absence of a definitive
      theory, this exploratory work sets out, via grounded theory, to shed some light
      on the methods used every day by nurses to make ethical decisions in the clinical
      area. The data show that some factors, such as doctors, colleagues and the
      organization, profoundly influence ethical decision making. The informants used
      both care and justice to formulate decisions, which is known as the combined
      approach. As a result of these findings, this article concludes with tentative
      suggestions and recommendations for practice.

PMID- 9616613
TI  - The limits of confidentiality.
AB  - Two conditions are commonly taken to constitute an obligation of confidentiality:
      information is entrusted by one person to another; and there is an express
      understanding that this will not be divulged. This conception of confidentiality,
      however, does not match much of the practice of health care. Health care
      practitioners would, for example, hold themselves to be under an obligation of
      confidentiality in situations where neither of these conditions obtain. The
      discussion proposes, therefore, two additional grounds for confidentiality. This
      is in order to clarify, in general terms, the scope of this obligation (i.e. to
      clarify at what point confidentiality can be said to have been broken). The
      'limits of confidentiality', it is argued, are set by the wishes of the client
      or, where these are not known, by reference to those whose right and need to know
      relate to the care of the client. Anonymous references to the client outside this
      limit may not be breaches of confidence; whether they are or not depends, it is
      suggested, on if such reference is responsible.

PMID- 9616614
TI  - Noncompliance by patients: a response to professor Dimond.
AB  - A recent article published in Nursing Ethics, written by Professor Bridgit
      Dimond, highlighted the topic of noncompliance by patients and attention was
      drawn to a number of issues relevant to health care professionals. In this
      response, some specific challenges facing nurses are considered in the light of
      Professor Dimond's arguments. In doing so, the notion of compliance as an
      appropriate concept in modern nursing practice is questioned. The recommendations
      to emerge include strategies to consider patient response to treatment regimens
      in the form of adherence to health care advice through negotiated therapy. The
      claimed benefits of health care recommendations are considered and caution about
      iatrogenesis is advised.

PMID- 9616616
TI  - A uniform reaction.

PMID- 9616615
TI  - A new position paper on educating nurses.

PMID- 9616617
TI  - Danger: change at work can damage your health.

PMID- 9616618
TI  - UKCC review: talking back.

PMID- 9616619
TI  - Communication breakdown.

PMID- 9616620
TI  - Between the lines.

PMID- 9616621
TI  - Chemotherapy by catheter.

PMID- 9616622
TI  - Tuberculosis: treating multi-drug resistance.

PMID- 9616623
TI  - Research in the clinical area: the ethical issues.
AB  - Healthcare professionals have a duty to undertake research, say the authors of
      this article, yet the patient's perspective is rarely considered. Here, they
      review the ethical aspects of clinical research.

PMID- 9616624
TI  - Patients' information needs in intensive care and surgical wards.
AB  - Meeting the information and psychosocial support needs of surgical patients who
      have been in intensive care can contribute significantly to their recovery. In
      this article, the author examines the nursing opportunities for meeting these
      needs and suggests how they can be addressed.

PMID- 9616625
TI  - Percutaneous endoscopic gastrostomy (PEG).
AB  - In the form of a case study that illustrates the procedure of percutaneous
      endoscopic gastrostomy (PEG), this article examines the implications of feeding
      patients by identifying the professional, legal, and moral issues that are
      involved.

PMID- 9616626
TI  - Pressure sore incidence: a strategy for reduction.
AB  - In this article, the author discusses how the Walsgrave Hospitals NHS Trust
      implemented a strategy to reduce the prevalence of hospital-acquired pressure
      sores. The role of the tissue viability nurse is emphasised as is the development
      of a staff education programme.

PMID- 9616627
TI  - Leg ulceration and clinical effectiveness: nurse-led clinics.

PMID- 9616629
TI  - Reducing sick leave by just 1% would save the NHS 140m pounds.

PMID- 9616628
TI  - Postoperative care--2.

PMID- 9616630
TI  - Mr Brown cuts the cake.

PMID- 9616631
TI  - A light goes out.

PMID- 9616632
TI  - Afghanistan's gender apartheid.

PMID- 9616633
TI  - Dial N for nurses.

PMID- 9616635
TI  - Using traction.

PMID- 9616634
TI  - Mending broken bones.

PMID- 9616636
TI  - Shaking babies.

PMID- 9616637
TI  - Day in day out.

PMID- 9616638
TI  - Daytime well spent.

PMID- 9616639
TI  - The ferret files.

PMID- 9616640
TI  - A leading question.

PMID- 9616641
TI  - On the beat.

PMID- 9616642
TI  - Reducing paperwork in a medical assessment unit.

PMID- 9616643
TI  - A healthy living centre in the community.

PMID- 9616644
TI  - Screening for neuroleptic side-effects.

PMID- 9616645
TI  - Voice restoration prostheses: the options.
AB  - The development of voice restoration systems means that people requiring
      laryngectomy have a better chance of being able to speak again after surgery. In
      the first of two articles the author discusses the surgical procedure and the
      various devices available. The second article in next week's Nursing Times looks
      in detail at the benefits of the new Provox 2 system.

PMID- 9616646
TI  - Pressure-sore prevention policies.

PMID- 9616647
TI  - The future of nursing and midwifery education.

PMID- 9616648
TI  - Trust mergers and you.

PMID- 9616649
TI  - Killing with care.

PMID- 9616650
TI  - The integration of hypnotherapy with mainstream medical techniques.

PMID- 9616651
TI  - Pressure points.

PMID- 9616652
TI  - The long-term care of older people.

PMID- 9616653
TI  - Complementary options.

PMID- 9616654
TI  - Piercing the pain.

PMID- 9616656
TI  - Bars to health.

PMID- 9616655
TI  - Slimy little suckers.

PMID- 9616657
TI  - Who loves you?

PMID- 9616658
TI  - Face to face. Interview by Adam Legge.

PMID- 9616659
TI  - Signs and symptoms of systemic lupus erythematosus.

PMID- 9616660
TI  - An easier way to speak again.
AB  - This article looks in detail at evaluation of the use of the Provox 2 voice
      prosthesis. Use of the device in selected patients has had a number of benefits
      including less mucus production, less awareness of the valve, reduction in the
      effort needed to produce sound, and easy and quick removal and insertion of the
      device.

PMID- 9616661
TI  - The care programme approach.

PMID- 9616662
TI  - Breast cancer: giving women a more proactive role.

PMID- 9616663
TI  - Mucosal immunology of the upper airways: an overview.

PMID- 9616664
TI  - The microbial ecology and immunology of the adenoid: implications for otitis
      media.
AB  - The nasopharyngeal tonsil, or adenoid, is a major inductive site for the
      synthesis of J-chain-positive B cells that may migrate to other areas of the
      upper respiratory tract, such as the nasal mucosa, the parotid gland, the
      lacrimal gland, and the middle ear during inflammation. The production of
      secretory IgA by both the nasopharyngeal tonsil and the nasal mucosa plays a
      major role in local immune protection against bacteria and viruses. The release
      of cytokines from Th1 and Th2 lymphocytes must be appropriate for B cells to
      produce IgA. The factors or mechanisms responsible for this are not, at present,
      known, but it appears that there is a difference in the profiles of cytokine
      secretion by Th1 and Th2 lymphocytes in the adenoids in both otitis-prone, as
      well as nonotitis-prone children. We have suggested that if this specific immune
      system does not protect the host from invasion by potential pathogens, there are
      other modalities of therapy to protect the nasopharynx from colonization with
      pathogenic bacteria or viruses. These include the production of specific
      antibodies against bacterial surface proteins that have been identified as mucin
      binding proteins. Alteration of the microbial flora with commensal organisms such
      as viridans streptococci can be utilized. These alpha-hemolytic streptococci
      probably function by producing an acid environment that prevents colonization of
      organisms such as nontypeable H. influenzae. Finally, the induction of specific
      SIgA by conserved outer membrane protein antigens of potential pathogens may be
      another strategy in the prevention of colonization of potential bacterial
      pathogens in the nasopharynx.

PMID- 9616665
TI  - The immunology of the host-parasite relationship in the nasopharynx.

PMID- 9616666
TI  - Immunology of the middle ear: role of local and systemic antibodies in clearance
      of viruses and bacteria.

PMID- 9616667
TI  - The role of IgE-mediated immunity in otitis media: fact or fiction?
AB  - As both OME and allergic rhinitis are common among young children, these
      disorders are occasionally seen in the same patients. Many clinical and
      experimental studies have denied the allergic etiology of OME, although type I
      allergic reactions in the nose cause tubal obstruction without inducing MEE
      because the induced obstruction remains for a short duration. An animal model
      study demonstrated that allergy-induced tubal obstruction disturbs the clearance
      of MEE significantly. Since a clinical and an experimental study showed the
      efficacy of allergic treatment in patients or animals having both diseases,
      allergy and OME should be treated simultaneously in patients with both diseases.
      Viral infections of the upper respiratory tract induce viral-specific IgE
      antibodies, which may cause mucosal inflammatory reactions similar to those seen
      in type I allergy. Viral infection also triggers bacterial infection.
      Consequently, viral infection is a critical factor in the etiopathogenesis of
      OME.

PMID- 9616668
TI  - Immunological deficiency in "otitis-prone" children.

PMID- 9616669
TI  - Are there immunological or genetic markers that can predict recurrent acute
      otitis media?

PMID- 9616670
TI  - The molecular biology of bone resorption due to chronic otitis media.

PMID- 9616671
TI  - Interactions between the middle ear and the inner ear: bacterial products.
AB  - The round-window membrane (RWM) is extremely thin and is the only soft-tissue
      barrier between the middle ear and the inner ear. Under inflammatory conditions
      of the middle ear the various layers of the triple-layered RWM undergo
      characteristic changes parallel to the changes of the middle-ear mucosa. Several
      studies report that bacterial products, exo- and endotoxins, from bacteria
      invading the middle ear may result in profound inflammatory changes in the inner
      ear, followed by severe damage to the inner-ear function. The present review, in
      which we summarized experimental and clinical observations, on bacterial products
      in interactions between the middle and inner ear, focused on: 1. Bacteria and
      bacterial products in an inflamed middle ear that may influence inner-ear
      function. 2. RWM structure and RWM permeability under the influence of bacteria
      and bacterial products. 3. Morphological and functional inner-ear effects of
      bacterial infection of the middle ear, and the possible mechanisms involved. 4.
      Future studies to be directed in this field.

PMID- 9616672
TI  - Effect of streptomycin and gentamicin on the inner ear.

PMID- 9616673
TI  - Effects of inflammatory mediators on middle ear pathology and on inner ear
      function.

PMID- 9616674
TI  - Role of viruses in middle-ear disease.
AB  - Taken together, there is ample evidence suggesting a role for viruses in the
      pathogenesis of OM. This evidence comes from numerous studies performed in
      animals and in vitro cell cultures, as well as in adults and children with URI
      and OM. Viruses induce host immune and inflammatory responses that result in
      pathology of the ET and the middle ear, and predispose the host in various ways
      to secondary bacterial infection. A suggested mechanism for the pathogenesis of
      OM following respiratory viral infection is presented in Figure 1.

PMID- 9616675
TI  - Summary: recent developments in the immunology of otitis media.

PMID- 9616676
TI  - Immunopathology of the inner ear: an update.
AB  - We have reviewed the events of an inner-ear immune response. The perilymph
      contains antibody, presumably derived from the systemic circulation and CSF,
      which would allow for neutralization and help with opsonization and complement
      fixation. The endolymphatic sac contains immunocompetent cells capable of
      processing and presenting viral or bacterial antigen, potentiating the immune
      response, attacking the invaders directly or attacking infected cells, and
      developing immunoglobulin responses in situ. The early release of mediators such
      as IL-2 likely emanate from the endolymphatic sac and result in potentiation and
      regulation of the response and may assist in changes in the SMV, including
      expression of ICAM-1, which aid in the egress of immune cells from the systemic
      circulation. PMNs arrive first, followed by T cells and B cells, with secretion
      of specific antibody a relatively late event. Concomitant with the increase in
      cellular constituents is the formation of a dense extracellular matrix. The inner
      ear appears to have remarkable difficulty in clearing this matrix, ultimately
      resulting in ossification. The immune response is unfortunately deleterious to
      the inner ear, resulting in degeneration of the organ of Corti, stria vascularis,
      and spiral ganglion. Hearing loss is consistently seen following sterile and
      virally induced labyrinthitis. The inner ear also appears to be a target for
      autoimmune disease. While inner-ear damage has been described as part of non
      organ-specific autoimmune disease, specific disease against the hearing apparatus
      is also likely. Experimental paradigms have allowed alterations of both the
      afferent and efferent limbs of this response; ultimately, with the hope that we
      can alter the course of the response and the subsequent damage in patients.

PMID- 9616677
TI  - Immune-mediated sensorineural hearing loss with or without endolymphatic hydrops:
      a clinical and experimental approach.
AB  - Since 1979, when McCabe first described a pattern of bilateral sensorineural
      hearing loss (SNHL) characterized by a rapid progression over days to weeks, the
      postulated autoimmune basis of this disease remains unknown. Various attempts
      have been made to develop the best assays that will clinically confirm the
      diagnosis and will help identify those patients who may respond to
      immunosuppressive therapy. The Western blot assay has now been widely applied by
      different research groups. It has been suggested that antibody to the 68-kD
      protein is most closely associated with this disorder. Recent analyses suggest
      that the protein of interest is probably a heatshock protein (hsp 70) with this
      molecular weight. This disease pattern of rapidly progressive bilateral SNHL
      presents itself clinically as a different disease than endolymphatic hydrops with
      fluctuating SNHL, and it is most often associated with vertigo and roaring
      tinnitus. Meniere's disease may be also immune-mediated, but lacks an autoimmune
      basis. Its etiopathogenesis is different. A critical review of our own Western
      blot analyses from patients with either idiopathic rapidly progressive SNHL (N =
      33), sudden deafness (N = 53), or other SNHL forms (N = 71) is presented. Immuno
      suppressive treatment responses were evaluated. A new concept of immune-mediated
      endolymphatic hydrops was also further developed on the basis of recent
      experimental data and earlier clinical observations in order to focus on another
      aspect of this most intriguing inner-ear disease.

PMID- 9616678
TI  - Systemic autoimmune diseases associated with hearing loss.

PMID- 9616679
TI  - Clinical management of immune-mediated inner-ear disease.

PMID- 9616680
TI  - The cochlear protein antigens 28 kd and 30 kd, and their antibodies in Meniere's
      disease.

PMID- 9616681
TI  - Molecular basis of type II collagen autoimmune ear diseases.

PMID- 9616682
TI  - Lymphocyte trafficking to the inner ear.

PMID- 9616683
TI  - The endolymphatic sac as the immunocompetent organ of the inner ear.

PMID- 9616685
TI  - Induction of an inner-ear-specific autoreactive T-cell line for the diagnostic
      evaluation of an autoimmune disease of the inner ear.
AB  - Different patterns of sensorineural hearing loss with a potential improvement in
      auditory function following immunosuppressive therapy might be caused by an
      isolated autoimmune disease of the inner ear. Because of the lack of well-defined
      detection methods to identify autoimmune processes within the inner ear and the
      fact that the human inner ear is one of the few organs of the body not amenable
      to diagnostic biopsy, there has been great interest in developing animal models.
      Previous studies found evidence that this entity might be cellular mediated. By
      heterologeous immunization of inbred Lewis rats with inner-ear tissue, an
      autoreactive inner-ear-specific T-cell line was established. After passive
      transfer of these cells, a labyrinthitis was induced in recipient animals. The
      experimental design can serve as an animal model for a cellular-mediated
      autoimmune disease of the inner ear. Further studies have to split the cochlear
      proteins and to identify the protein with the strongest autoimmunological
      potency. After biotechnical production of this protein, a clinical test to
      diagnose an autoimmune disease of the inner ear in man should be possible.

PMID- 9616684
TI  - Human autoantibodies and monoclonal antibody KHRI-3 bind to a phylogenetically
      conserved inner-ear-supporting cell antigen.
AB  - Autoimmunity is thought to be one cause of sensorineural hearing loss (SNHL).
      Sera from patients with rapidly progressive hearing loss have been shown to
      contain antibodies to a 68-kD protein in heterologous inner-ear tissue. Using
      guinea pig inner-ear tissue as the antigenic substrate and either Western blot or
      immunofluorescence (IF) or both, we tested sera from 74 patients suspected to
      have autoimmune hearing loss for inner-ear antibodies. Sera from 73 patients were
      tested by Western blot, and sera from 36 were tested by IF. Thirty-seven of 73
      (51%) had antibody to a 68-70-kD protein by Western blot. Sera positive by IF
      stained supporting cells with a staining pattern like that previously observed
      with the KHRI-3 monoclonal antibody. There was concordance between Western blot
      and IF assays. Of 36 patients tested by both assays, 29/31 (94%) that were
      positive in Western blot were also positive by IF, three were negative by both
      tests, and two each were positive by one assay but negative by the other.
      Absorption of patient sera with human inner-ear tissue removed antibody
      reactivity to the guinea pig supporting cells, indicating that the antigen
      detected by the autoantibody is also present in the human inner ear. Absorption
      with an equal volume of white or red blood cells from the tissue donor did not
      remove the antibody reactivity to inner ear, showing that the absorption by inner
      ear tissue is specific. Sera from three patients positive in both assays also
      stained a 68-70-kD inner-ear protein immunoprecipitated by the KHRI-3 monoclonal
      antibody, indicating that the monoclonal and human antibodies recognize the same
      antigen. The results support the hypothesis that patients with autoimmune
      sensorineural hearing loss produce autoantibodies to an inner-ear supporting cell
      antigen that is phylogenetically conserved and defined by the murine monoclonal
      antibody KHRI-3. Since KHRI-3 can induce hearing loss after infusion into the
      inner ear, it is likely that autoantibodies with the same antigenic target are
      also pathogenic in humans.

PMID- 9616686
TI  - Auditory findings in subjects with immunomediated sensorineural hearing loss.

PMID- 9616687
TI  - Measles, mumps, and sensorineural hearing loss.

PMID- 9616688
TI  - Meniere's disease and autoimmunity.

PMID- 9616689
TI  - Viral theory for Meniere's disease and endolymphatic hydrops: overview and new
      therapeutic options for viral labyrinthitis.

PMID- 9616690
TI  - Cytomegalovirus antibodies in endolymphatic sac biopsies of patients with
      endolymphatic hydrops and Meniere's disease.

PMID- 9616691
TI  - Sudden hearing loss in childhood consequent to hepatitis B vaccination: a case
      report.

PMID- 9616692
TI  - Screening patients affected by common variable immunodeficiency.
AB  - Chronic immunoglobulin administration decreases the incidence of bronchial and
      pulmonary infections in patients affected by chronic variable immunodeficiency
      (CVI). In this study, an ENT screening was carried out in 22 patients affected by
      chronic variable immunodeficiency and treated with chronic immunoglobulin
      administration. All the patients underwent ENT physical examination, nasal
      endoscopy by fiberoptics, mucociliary transport test (MTT), anterior
      rhinorheomanometry (RRM), nasal provocation test with cold water (ANPT),
      audiometry and impedentiometry, olfactory evaluation, and paranasal sinus X rays.
      Dysphagia was present in 91% of the patients, nasal secretion and obstruction in
      77%, and hypoacusia, tinnitus, and otodinia in 57%. Rhinitis and pharyngitis were
      observed in 86% of the patients, and serous middle ear effusion in 50%. Confirmed
      maxillary sinusitis was observed in five patients. Hyposmia was observed in 50%
      of the patients. MTT was significantly longer in the patients than in the
      controls (18.0 +/- 10.5 vs. 11.2 +/- 2.4 min; p < .05). Nasal resistance was
      lower in patients than in controls (0.46 +/- 0.32 vs. 1.11 +/- 0.22 Pa/L.s-1; p <
      .001). ANPT was positive in 9 patients out of 25 versus 1 control out of 15 (p <
      .05). Finally, seven patients were affected by transmissive hypoacusia, and one
      patient by neurosensorial hypoacusia. Our results suggest that chronic
      immunoglobulin administration in CVI patients is not effective against ENT
      disorders, probably because of the important role played by nasal
      hyperreactivity. Frequent ENT examination and early treatment of ENT disorders
      are therefore suggested in order to prevent chronic disease.

PMID- 9616693
TI  - Summary: progress in inner-ear immunology.

PMID- 9616694
TI  - Vaccination against middle-ear bacterial and viral pathogens.
AB  - Considerable evidence suggests that otitis media (OM) can be prevented by
      systemic immunization. Building on the highly effective H. influenzae type b
      (Hib) conjugate vaccine technology, pneumococcal conjugate vaccines are being
      developed to circumvent T-independence of these antigens and provide durable
      immunity at a very young age. Several pneumococcal conjugate vaccines are
      currently in clinical testing. Potential vaccine antigens of nontypable H.
      influenzae (NTHi) include OMP, HMW, pili, and fimbriae. Several OMPs show
      extensive homology among strains, but surface, determinants of others are highly
      variable so that antibodies to surface epitopes of one strain will not bind to
      surface epitopes of another. Several M. catarrhalis OMP and HMW antigens have
      vaccine potential, but no functional correlates of protection have been
      identified, and there is no clear evidence that antibody to M. catarrhalis is
      associated with OM protection. Attenuated viral vaccines also hold promise of
      preventing childhood OM. Two clinical trials with killed influenza vaccines have
      shown a significant reduction in OM among vaccine recipients compared to control
      children during periods of high influenza disease activity in the community.
      Passive immunoprophylaxis also has potential for preventing OM. Human bacterial
      polysaccharide immune globulin was protective for pneumococcal OM in children and
      in the chinchilla OM model. High-dose respiratory syncytial virus-enriched
      immunoglobulin reduced the incidence and severity of RSV lower respiratory tract
      infection in high-risk children. Passive immunoprophylaxis may also be effective
      in children with specific immune deficiencies, such as IgG2 deficiency, and
      patients who fail to respond to vaccines.

PMID- 9616695
TI  - Mechanisms of recurrent otitis media: importance of the immune response to
      bacterial surface antigens.
AB  - Otitis-prone children experience recurrent episodes of otitis media due to
      nontypeable H. influenzae (NTHI). A protective immune response occurs following
      infection, but this immune response is specific for the infecting strain, leaving
      the child susceptible to infection by other strains of NTHI. Little is known
      about the mechanism by which a strain-specific antibody response occurs to
      nonencapsulated bacteria. To explore the mechanism by which this strain-specific
      response occurs, animals were inoculated with whole bacterial cells and the
      antibody response was studied. The antibody response was predominantly directed
      to a highly strain-specific, immunodominant surface loop on the major outer
      membrane protein. This exquisitely restricted immune response leaves the host
      susceptible to recurrent infections by many strains of NTHI. The ability of the
      bacterium to direct the host to make a strain-specific antibody response has
      important implications in understanding the immune response to otitis media due
      to NTHI and in designing strategies for vaccine development.

PMID- 9616697
TI  - Bioartificial organs as outcomes of tissue engineering. Scientific and regulatory
      issues.

PMID- 9616696
TI  - An introduction to the genetics of normal and defective hearing.
AB  - The recent rapid development of molecular biology techniques applied to the
      genetics of normal and defective hearing shed a new light on old questions
      regarding hearing and deafness. Genes are DNA sequences that determine
      characteristics, normally by specifying the sequence of aminoacids in a protein.
      The majority of genes is located in the chromosomes (human chromosomes have
      perhaps 80,000 pairs of genes). In addition there are 37 mithochondrial genes
      which are inherited only from the mother. One method used to identify candidate
      genes based on their function or pattern of tissue expression involves the
      construction of cDNA libraries from the target organ or tissue, in this case from
      the cochlea. The construction and characterization of cochlear cDNA libraries
      from humans and other species provide an important resource for rapid
      identification of cochlear genes involved in normal hearing and hearing
      disorders. Studies of the molecular genetics of the inner ear are hampered by the
      relative inaccessibility of the cochlea, by the limited number of cochlear and
      vestibular cells, and by our inability to maintain many of these cell types in
      long-term cultures. Several rodent inner-ear cDNA libraries and a human foetal
      cochlear cDNA library have already been constructed. Human and rodent cochlea
      subtracted cDNA libraries are very useful for identifying genes controlling the
      development and maintenance of hearing. cDNA libraries constructed at different
      stages of development, and subtracted from each other, could be instrumental in
      identifying genes important at each stage of cochlear development. In addition,
      these libraries have the potential of fostering the identification of other
      proteins unique to the cochlea and will contribute to the identification,
      characterization, and functional analysis of these cochlea-specific proteins.
      Another important application of cDNA libraries is in identifying hearing-loss
      genes. Once the candidate gene for a given type of hearing loss is cloned and
      decoded, the structure of its protein product can be determined. This will
      provide insights into the biochemical function of the gene product in normal
      cochlear tissue, and will show why the genetic mutation results in hearing loss,
      that is, the recent identification of the myosin VIIa gene in Usher type IB. In
      addition, through the use of homologous recombination and transgenic technology,
      in vivo mouse models of inner-ear genetic disorders can be created. To date, 350
      different genetic conditions associated with hearing impairment have been
      described, and during the past five years several of the genes involved in these
      form have already been mapped and identified.

PMID- 9616698
TI  - Regulatory considerations in the development of encapsulated cells.

PMID- 9616699
TI  - Design and synthesis of new biomaterials via macromolecular substitution.

PMID- 9616700
TI  - Elastic protein-based materials in tissue reconstruction.
AB  - In natural tissues, cells form multiple attachment sites to their extracellular
      matrix. By means of those attachments, cells deform as the tissue deforms in
      response to the natural mechanical stresses and strains that the tissue must
      sustain during function. These mechanical forces are the energy input that
      instruct the cells to produce the extracellular matrix sufficient to sustain
      those forces. Thus, an ideal artificial material should have both the attachment
      sites for the natural cells and a compliance that matches the natural tissue.
      Elastic protein-based polymers have been designed to provide both cell attachment
      sites and to exhibit the required elastic modulus of the tissue to be replaced.
      Thus, this introduces the potential to design a temporary functional scaffolding
      that will be remodeled, while functioning, into a natural tissue. A feasibility
      study applies this concept to the problem of urinary bladder reconstruction in
      terms of the filling and emptying of a simulated bladder comprised of an elastic
      protein-based matrix containing cell attachment sites with human urothelial cells
      growing out onto the dynamic matrix. Furthermore, the elastic protein-based
      materials themselves have been designed to perform the set of energy conversions
      that occur in living organisms and, in particular, to convert mechanical energy
      into chemical energy with the result of chemical signals of the sort that could
      provide the stimuli to turn on the genes for producing the required extracellular
      proteins.

PMID- 9616701
TI  - Synthesis of biodegradable polymers for controlled drug release.

PMID- 9616702
TI  - HPMA-based biodegradable hydrogels containing different forms of doxorubicin.
      Antitumor effects and biocompatibility.
AB  - Novel hydrogels based on N-(2-hydroxypropyl)methacrylamide (HPMA) and N,O
      dimethacryloylhydroxylamine containing either doxorubicin (DOX) or water-soluble
      HPMA carrier-bound doxorubicin (P-GlyPheLeuGly-DOX; HPMA-DOX) were synthesized.
      The cross-linkages are susceptible to hydrolytic cleavage at physiological pH
      7.4. Hydrogels in the form of rods or discs loaded with DOX or P-GlyLeuGly-DOX
      were implanted subcutaneously on the back of C57BL/10 mice on day 1 or on day 9
      after inoculation with EL4 mouse T-cell lymphoma. The implanted hydrogels varied
      in the total load of DOX and rate of hydrolysis, which is dependent on the
      crosslinking density of the gels. The effect of HPMA based hydrogels containing
      DOX or HPMA carrier-bound DOX on tumor growth, animal life span, leukocyte
      populations in peripheral blood and bone marrow function evaluated by
      reticulocyte count was investigated. It was shown that: a) DOX and HPMA carrier
      bound DOX administered in the form of HPMA-based hydrogels has better antitumor
      activity against experimental EL4 mouse T-cell lymphoma than soluble forms of the
      drug, b) hydrogels with shorter degradation rate (16-17 h) show better antitumor
      activity than hydrogels with longer duration time (48-52 h), c) the therapeutic
      effect of hydrogels with rate 16-17 h is directly related to the doxorubicin
      content; the higher the doxorubicin content, the better antitumor activity, d)
      the gel containing free doxorubicin showed significant antitumor activity even
      when implanted on day 9, i.e., in the time when tumor growth is already
      established, e) the hydrogel matrix without drug does not induce release of IL-1
      or IL-6 into peripheral blood, does not induce formation of antibodies, and it is
      not mitogenic. Use of doxorubicin in the form of HPMA-based hydrogels allows a
      several-fold increase in the administered dose compared to soluble forms without
      detectable serious toxic side-effects.

PMID- 9616703
TI  - Synthetic strategies for the preparation of precursor polymers and of
      microcapsules suitable for cellular entrapment by polyelectrolyte complexation of
      those polymers.
AB  - The production of microcapsules suitable for the entrapment of mammalian cell by
      means of polyelectrolyte complexation has, of a necessity, led to the development
      of novel strategies for the preparation of relatively bioinert polymers which
      complex efficiently under unique conditions to produce a mechanically resilient
      membrane with efficient transport properties. In this communication we relate a
      brief overview of capsule-membrane forming systems for the immunoisolation (or
      potential immunoisolation) of mammalian cells, which are based upon the
      complexation of polyelectrolyte (PE) polymers; with emphasis on precursor
      synthesis and relationships between precursor polymer structure and capsule
      membrane stability.

PMID- 9616704
TI  - Anionic polymers for implantation.
AB  - The biocompatibility of hydrogels containing carboxylate anions was studied by a
      panel of tests in vitro and in vivo. In comparison with other types of similar
      hydrogels, those with COO- anions induced a lower extent of foreign body
      reaction, and their systemic effect on the immune system also seems lower. The
      biomimetic effect of carboxylate anions on biocompatibility of synthetic
      materials could be explained by a similar biomimetic effect of N-acetylneuraminic
      acid inhibiting the non-self recognition of bacterial cells by non-specific
      immunity. The encouraging long-term results of clinical trials of intraocular
      lenses prepared from copolymer of 2-hydroxyethyl methacrylate and sodium
      methacrylate support this hypothesis.

PMID- 9616705
TI  - Scanning probe microscopy for the characterization of biomaterials and biological
      interactions.
AB  - The scanning probe microscopies provide a unique view of biological and
      biomedical systems at a nanoscale appropriate to appreciate molecular events. The
      advent of these methods has brought the ability to acquire quantitative
      information at the molecular level. Given the proliferation of microscopes and
      associated methods, the probability for important discoveries is high. If
      tempered with an appreciation for the potential for artifacts, the SPMs may
      revolutionize our view of biological systems and biomaterials interactions with
      those systems.

PMID- 9616706
TI  - XPS and SIMS studies of surfaces important in biofilm formation. Three case
      studies.
AB  - Although the importance of cell adhesion to synthetic surfaces is well
      established, a detailed description of the molecular interactions important in
      adhesion still eludes researchers. In order to fully understand the adhesion
      events that lead to biofilm formation on synthetic materials it is necessary to
      have an accurate understanding of the synthetic material surface, to understand
      the composition and orientation of biopolymers that adsorb to the material, and
      to understand the surface chemistry of cells that ultimately adhere. The simplest
      of these three surfaces, the synthetic material, commonly presents a profound
      level of complexity and presents a wide variety of chemical functional groups in
      many orientations at the surface. The conditioning film surface and cell surface
      show yet greater levels of complexity. The three case studies presented here
      demonstrate that XPS and SIMS are valuable techniques for studying all three of
      these surfaces. They are not only capable of providing an accurate analysis of
      the synthetic polymer surface but they are also sensitive to the composition and
      orientation of biomolecules. The potential for rapid characterization of cell
      surfaces with SIMS demonstrated in the final case study suggests that intelligent
      application of these techniques may ultimately aid in answering the elusive
      question of how cells adhere to synthetic surfaces.

PMID- 9616707
TI  - Bacterial infection of biomaterials. Experimental protocol for in vitro adhesion
      studies.
AB  - Some of the more common reactor systems and novel diagnostic tools employed in
      the study of bacterial cell adhesion and biofilm formation have been described.
      Sampling and experimental requirements are shown to greatly influence the design
      and construction of a biofilm reactor. As analytical techniques evolve, the
      capability to non-invasively follow the development of biofilms and to assess the
      attached cell reactivity has increased. Both non-invasive and invasive diagnostic
      methods affect the type and design of biofilm flow reactor with both types of
      analyses providing complementary information on biofilm processes. To correctly
      interpret the contribution of a specific rate process to the net accumulation of
      cells at a substratum, one requires a reactor system devoid of any mass transfer
      limitations and a process analysis approach to allow for the correct collection
      and analysis of data.

PMID- 9616708
TI  - Fibrinogen-dependent adherence of macrophages to surfaces coated with
      poly(ethylene oxide)/poly(propylene oxide) triblock copolymers.
AB  - The role of fibrinogen in the adherence of macrophages to polymer surfaces was
      studied using a human cell line (THP-1 cells) and polystyrene-divinylbenzene
      beads coated with poly(ethylene oxide)/poly(propylene oxide) copolymers of the
      form PEO alpha PPO beta PEO alpha. The amphiphilic character of the surface of
      the beads was varied using a series of copolymers with constant PPO core lengths
      but different PEO segments. Fibrinogen-dependent adherence of
      monocytes/macrophages to the modified beads was then assessed. The adherence of
      THP-1 cells to copolymer-coated beads correlates well with the amount of
      fibrinogen bound to the beads. Those beads coated with the most hydrophobic
      surfactant molecules bound the most fibrinogen and the most cells. On these
      surfaces, the concentration of fibrinogen was less than half that of the protein
      on unmodified beads. Despite the lower amount of bound fibrinogen, the number of
      adherent cells was 37% greater than the number of adherent cells on fibrinogen
      coated, copolymer-free beads. Beads coated with the most hydrophilic surfactants
      bound just 10% the amount of fibrinogen bound to unmodified beads. On these
      surfaces, the number of adherent cells was decreased by approximately 25% with
      respect to the number of cells bound to beads coated with fibrinogen alone. We
      propose that the hydrophobic surfactant molecules may act as inflammatory agents
      by facilitating fibrinogen-dependent cellular adhesion.

PMID- 9616709
TI  - Effect of external oxygen mass transfer resistances on viability of
      immunoisolated tissue.

PMID- 9616710
TI  - Controlled drug release from self-catalyzed poly(ortho esters).

PMID- 9616711
TI  - Factors determining hydrogel permeability.
AB  - Developing hydrogel membranes and coatings of appropriate permeability
      characteristics is key to the success of a number bioartificial organ
      technologies. Key principles relevant to the design and application of hydrogels
      for such applications were reviewed. The first key point is that permeability is
      a function of both transport and thermodynamic properties, the diffusion
      coefficient and partition coefficient, respectively, and that these parameters
      can be evaluated separately. Although the aspect of partitioning often emphasized
      is size exclusion, this review points out that many other relevant interactions
      come into play, especially hydrophobic and electrostatic interactions, and that
      these phenomena can dominate size exclusion. Similarly, while the diffusion
      coefficient also is strongly dependent upon size, other interactions can also
      cause diffusivity to deviate from theories which consider only solute size and
      gel swelling. For example, the heterogeneity of hydrogel networks can result in
      permeabilities that fail to decline as much as might be anticipated if networks
      were uniform.

PMID- 9616712
TI  - Permeability assessment of capsules for islet transplantation.
AB  - Despite considerable progress in the development of immunoisolation devices, the
      optimal permeability of such devices is not known. This limitation stems partly
      from deficits in knowledge about which molecules should be allowed to traverse
      the semipermeable membrane and which molecules should be excluded, and also
      partly from experimental obstacles that have prevented a systematic study of
      permeability. To determine the optimal permeability of immunoisolation devices,
      we have created a series of microcapsules (800 microM diameter) that span a broad
      range of molecular exclusion limits yet are identical in wall thickness and
      chemical composition. Capsule permeability was precisely defined by two
      complementary methods--size exclusion chromatography (SEC) and a newly developed
      methodology to assess permeability of biologically relevant proteins. The entry
      of interleukin-1 beta-125I was significantly delayed, but not prevented, when the
      capsule exclusion limit was decreased from 230 kD to 3.2 kD, as determined by SEC
      with dextran standards. The influx of IgG was as predicted, based on the
      viscosity radius R eta of IgG and the capsule exclusion limit defined by SEC.
      Glucose-stimulated insulin secretion by encapsulated pancreatic islets did not
      differ as capsule permeability was decreased from a molecular exclusion limit of
      230 kD to 120 kD. These studies should assist in the design of immunoisolation
      devices by defining the permeability optimal for cell function and also should be
      applicable to any cell type or immunoisolation device.

PMID- 9616713
TI  - Modulation of surface and bulk properties of biomedical polymers.
AB  - The surface and bulk modulation of polymeric biomedical devices allows the full
      range of material properties to be exercised as demanded by custom applications.
      Polymeric biomaterials are finding greater use as relatively inert and even
      transient options and so therefore will require thorough processing analyses and
      the transfer of technology from nonbiomedical applications to the biomedical
      industry.

PMID- 9616714
TI  - Purification of polymers used for fabrication of an immunoisolation barrier.
AB  - A multistep extraction procedure has been tested for purification of natural and
      semi-synthetic polymers used for fabrication of an immunoisolation barrier for
      implanting animal cells. This procedure, originally described by Klock et al. for
      alginates, has been adapted for other gelling polymers to remove pyrogens
      (endotoxins) and mitogens. Several other steps have also been tested, resulting
      in a new and simple procedure for polymer purification, giving satisfactory
      levels of contamination. Endotoxin levels have been quantified by means of
      chromogenic and gelclot LAL methods. A simple calculation of the endotoxin
      permissible levels shows that the quality of purified polymers exceeds FDA
      specifications for implantable polymers.

PMID- 9616715
TI  - Mechanical characterization of biomaterials.
AB  - Experimental testing and computational modeling are two useful tools for
      mechanical characterization of biomaterials, providing insight into material
      stresses and strains and the possibility of mechanical failure and fatigue.
      Another interesting issue to consider, however, is tissue response to mechanical
      stress and strain and incorporation of that knowledge into design to create
      materials that form mechanically effective tissue-material interfaces in vivo.
      Experimental testing, computational modeling, and tissue response to stress and
      strain are discussed in the context of enhancing biomaterial design.

PMID- 9616716
TI  - The biochip. A new membrane bioreactor system for the cultivation of animal cells
      in defined tissue-like cell densities.
AB  - Based on the laminar structure of the human liver tissue, a high cell density
      membrane bioreactor was developed that emulates a cell layer thickness of 40
      microns. The "biochip" consists of a platinum-coated metal cell grid covered with
      two microfiltration membranes to form separate cell chambers of defined volume.
      Starting with a continuous chemostat process, the viability of a model suspension
      cell culture could be stabilized at 98%. In a second step these cells were
      transferred into the biochip system and were cultivated successfully for several
      days under tissue-like cell densities in a modified membrane holder under cross
      flow conditions.

PMID- 9616717
TI  - Artificial cells and bioencapsulation in bioartificial organs.
AB  - The most common use of artificial cells is for bioencapsulation of biologically
      active materials. Many combination of materials can be bioencapsulated. The
      permeability, composition and configurations of artificial cell membrane can be
      varied using different types of synthetic or biological materials. These possible
      variations in contents and membranes allow for large variations in the properties
      and functions of artificial cells.

PMID- 9616718
TI  - Selected aspects of the microencapsulation of mammalian cells in HEMA-MMA.
AB  - Microencapsulation of live mammalian cells is one means of creating hybrid
      artificial organs, like an artificial pancreas or an artificial liver. In
      addition to creating and developing the methodologies for enclosing cells within
      the appropriate semipermeable and biocompatible membranes, novel techniques are
      needed to assess the various features of the resulting capsules. The small size
      of a capsule or its heterogeneity can lead to additional complexities that go
      beyond the problem of examining cell behavior in the presence of biomaterials.
      These problems are illustrated here by comparison of protein release by
      microencapsulated HepG2 cells within large and small HEMA-MMA (hydroxyethyl
      methacrylate-methyl methacrylate) capsules, by assessment of the effect of
      processing conditions on HEMA-MMA microcapsule permeability to horseradish
      peroxidase at the individual capsule level, and by a confocal microscopy
      technique for assessing intracapsule cell viability.

PMID- 9616719
TI  - Microencapsulation of cells. Medical applications.

PMID- 9616720
TI  - Models of organ regeneration processes induced by templates.

PMID- 9616721
TI  - Neonatal porcine islets as a possible source of tissue for humans and
      microencapsulation improves the metabolic response of islet graft
      posttransplantation.

PMID- 9616722
TI  - Alginate-based microcapsules for immunoprotected islet transplantation.
AB  - Islet transplantation is a promising therapeutic approach for the treatment of
      insulin-dependent diabetes mellitus. Nevertheless, its broader clinical use is
      hampered by the shortage of human organ donors as well as the need for a
      permanent immunosuppressive drug therapy in order to avoid rejection.
      Microencapsulation shall help to overcome this problem by creating an
      immunoprotected transplantation site. Biocompatibility of the encapsulation
      material and the possible immuno-interaction of the grafted tissue and the host
      immune system need to be examined very carefully. In transplantation experiments,
      we could show that the long-term function of the graft is dependent on the
      species of the islet donor, indicating that there has to be a recognition of the
      encapsulated islet despite the encapsulation membrane. This could be confirmed by
      in vitro data in the mixed lymphocyte islet culture (MLIC). Moreover,
      morphological studies of the tissue reaction toward encapsulated syngeneic vs.
      allogeneic vs. xenogeneic encapsulated islets reveal that the greater the
      difference between donor and recipient species the greater the amount of fibrous
      tissue formation. Thus, for the outcome of transplantation experiments, not only
      the material-related biocompatibility but as well the reaction towards the whole
      device (consisting of the capsule plus the encapsulated tissue) are crucial.
      Therefore, immunoprotection does not only comprise the protection of the grafted
      tissue from the host immune effector mechanisms but as well the inhibition of the
      recognition of the graft by the host immune system.

PMID- 9616723
TI  - Alginate/polyaminoacidic coherent microcapsules for pancreatic islet graft
      immunoisolation in diabetic recipients.

PMID- 9616724
TI  - Transplantation of pancreatic islets.
AB  - The currently limited supply of human pancreatic glands, and the fact that
      multiple glands may be required to isolate sufficient numbers of islets to treat
      a single patient, indicate that techniques must be further developed and refined
      for xenografting of isolated islets from animal sources to diabetic patients. An
      increasing body of evidence using immunoisolation techniques strongly suggests
      that this will be achieved during the next few years. Several different types of
      systems employing selectively permeable membranes and matrix supports for cells
      have been successfully tested in animals, including devices anastomosed to the
      vascular system as arteriovenous (AV) shunts, tubular membrane chambers, and
      spherical micro- and macrocapsules. Results in diabetic animals indicate that
      these systems can function for periods of several months to > year without the
      use of any immunosuppression. Our data suggest that this approach has the
      potential not only to allow the transplantation of islets across wide species
      barriers, but that it can be achieved using injectable microreactors fabricated
      from biodegradable polymers. The use of these various immunoisolation systems to
      transplant islets and other cells and tissues offers the opportunity to
      revolutionize current therapy for many human disease.

PMID- 9616725
TI  - Immunoisolation of adult porcine islets for the treatment of diabetes mellitus.
      The use of photopolymerizable polyethylene glycol in the conformal coating of
      mass-isolated porcine islets.
AB  - Functional porcine islets, free of known pathogens, can serve as a source of
      insulin producing cells for the treatment of experimentally induced insulin
      dependent Diabetes Mellitus. Porcine islets can be conformally coated
      (microencapsulated) with a covalently linked, stable permselective membrane while
      maintaining islet viability and function. The PEG conformal coating is
      immunoprotective in a discordant xenograft animal model (porcine islets to rat).

PMID- 9616726
TI  - Application of AN69 hydrogel to islet encapsulation. Evaluation in streptozotocin
      induced diabetic rat model.
AB  - The polymer AN69 (polyacrylonitrile-sodium methallylsulfonate) is a reference in
      biocompatibility in the field of hemodialysis. Its use for the encapsulation of
      living cells has been already described, but this study is the first description
      of AN69 hydrogel-encapsulated islet isograft in streptozotocin (STZ) diabetic
      rats. The aim of this work is to evaluate the biocompatibility of the AN69
      hydrogel by comparison of the efficacy of free versus encapsulated islets
      transplanted to balance diabetes. Pancreatic islets are isolated from adult male
      Lewis rats by a standard collagenase digestion and purified on Ficoll density
      gradients. The AN69 hollow fiber is obtained by coextrusion of an 8% AN69
      collodion. The hollow fiber is filled with islets suspended in agarose at the
      final concentration of 10,000 islets/ml, closed with surgical clips and
      implanted. The recipients are rendered diabetic by intravenous injection of STZ.
      The experimental design includes 4 groups of 8 rats: group 1: control, group 2:
      diabetic rats intraperitoneally implanted with 6000 free islets, group 3:
      diabetic rats intraperitoneally implanted with 9000 encapsulated islets, group 4:
      diabetic control. Weight and fasting glycemia are evaluated twice a week,
      diuresis once a week. After free islet implantation, rat survival is improved
      with glycemia below 250 mg/dl during 22 days. Compared to group 2, the status of
      group 3 is better, with a glycemia below 250 mg/dl during at least 70 days. This
      tends to demonstrate the biocompatibility of AN69 and is the first step of the
      validation of the use of AN69 for living cell encapsulation.

PMID- 9616727
TI  - Treatment of severe liver failure with a bioartificial liver.
AB  - Orthotopic liver transplantation (OLT) is the definitive therapy for severe liver
      failure. However, many patients die before an organ becomes available, mostly
      from cerebral edema. To provide temporary liver support, we developed a
      bioartificial liver (BAL) based on porcine hepatocytes and a charcoal column.
      Fifty-four consecutive BAL treatments were carried out in three groups of
      patients: Group I (n = 15) patients presented with FHF were listed for emergent
      OLT, Group II (n = 3) patients with primary non-function (PNF) of their liver
      grafts required urgent re-transplantation and Group III (n = 10) patients with
      acute exacerbation of chronic liver disease were not candidates for OLT. Patients
      were managed in a critical care unit receiving maximal standard support. Each BAL
      treatment was conducted for 6 hours. In Group I, all patients showed significant
      neurologic improvement, intracranial pressure (ICP) decreased and cerebral
      perfusion pressure (CPP) increased; other significant improvements, included
      lowered plasma ammonia and liver enzymes and increased glucose. One patient
      recovered spontaneously without OLT, all other patients were "bridged" to OLT,
      and recovered. Group II: PNF patients showed similar benefits. Group III: Chronic
      liver patients demonstrated transient beneficial effects after BAL treatment(s),
      however, most (n = 8) eventually succumbed to sepsis and multiple organ failure
      as they were not candidates for OLT; two patients, recovered, later were
      successfully transplanted and survived. Our clinical experience demonstrates that
      the BAL can serve as a bridge to OLT in patients with acute liver failure.

PMID- 9616728
TI  - Molecular regulation of liver regeneration.

PMID- 9616730
TI  - Spheroid formation of hepatocytes using synthetic polymer.
AB  - It is known that hepatocytes show the different morphology depending on the
      surface condition of cultural substratum. The cells form a floating cell
      aggregate called spheroid on proteoglycan-coated or positively charged dishes.
      The liver cell functions are generally high and maintained for the long-term in
      the spheroid culture. Since spheroid morphology is preferable for the
      construction of a bioartificial liver, it is important to develop an effective
      method of preparing spheroids. In this regard, we examined a preparation method
      of functional spheroid-like cell-aggregates, in which a synthetic polymer,
      Eudragit was added to culture medium for inducing liver cell-aggregation. The
      cell-cell attachment of the aggregate was loose at the beginning of the culture,
      but it became tight and spheroids were formed 2-3 days after inoculation. When
      0.1% Eudragit was added to the medium, the liver functions such as albumin
      secretion, ammonia removal and urea synthesis were enhanced compared with
      monolayer and conventional spheroid cultures. The spheroid formation was also
      performed with suspension culture in a spinner flask. Approximately 80% of the
      cells inoculated formed spheroids by the addition of the polymer. Moreover, the
      polymer showed a protective effect from cell damage by agitation. Since this
      procedure does not require surface for cell attachment, a large amount of
      spheroids can be prepared in suspension culture.

PMID- 9616729
TI  - In vitro organogenesis of liver tissue.
AB  - The high metabolic rate of hepatocytes severely limits the mass of cells which
      can be transplanted without a vascular supply. We are developing an alternative
      approach in which vascularized tissue is grown ex vivo for anastamosis into the
      portal vein. Here, we discuss the key design issues for in vitro organogenesis of
      vascularized hepatic tissue, describe a fabrication approach for making complex
      degradable polymer scaffolds to organize cells in three dimensions on the scale
      of hundreds of microns, and demonstrate the feasibility of using these scaffolds
      for in vitro tissue organization in mixed-cell cultures.

PMID- 9616731
TI  - Non-autologous transplantation with immuno-isolation in large animals--a review.
AB  - Transplantation has become a successful method for the management of functional
      failure of a variety of tissues or organs. However, the majority of clinical
      transplantations use non-autologous allogeneic donor tissue implanted from one
      human to another. In order to prevent rejection of the allogeneic tissue, methods
      to overcome the immune barrier are necessary. Although prevention of organ
      rejection is currently achieved with pharmacological immune suppression, the
      undesirable side effects of this method have incited interest in novel methods to
      overcome the immune barrier. One such novel method of preventing immune reaction
      is immuno-isolation, in which the non-autologous tissues are physically isolated
      from the host tissues by placement in devices with perm-selective membranes. The
      membranes of these devices allow release of the therapeutic product required from
      the transplanted tissues, as well as diffusion of nutrients and waste necessary
      for survival of the non-autologous tissues. The membranes also prevent host
      immune mediators from contacting the non-autologous cells, thus preventing immune
      rejection. This technology has been tested for efficacy in large animal models,
      and is currently in the process of clinical trials in humans. This review will
      discuss the progress made in using immuno-isolation of non-autologous tissues in
      large animals. Immuno-isolation can be subdivided into two major areas of
      interest based on whether the non-autologous tissue used in the immuno-isolation
      device is genetically altered (gene therapy) or not. Studies using non
      genetically altered non-autologous cells for immune-isolation have been dominated
      by the use of pancreatic islet cells for the treatment of diabetes. This work has
      been tested in large animal models of diabetes, including canine and primate
      model animals, and human clinical trials are underway. As well, there has also
      been work on treatment of neurological disorders such as Parkinson's disease or
      chronic pain using non-autologous immuno-isolated adrenal chromaffin cells or
      dopaminergic PC12 cells in large animals such as sheep and primates. This work
      will be reviewed in detail as to the types of disorders, immuno-isolation devices
      used and the type of large animals involved. Immune-isolation for gene therapy is
      a more recently developed field of research. In this case, the non-autologous
      cells used are first genetically altered to secrete a recombinant therapeutic
      product before placement in the immune-isolation devices. Genetic engineering of
      the non-autologous cells is beneficial, as it allows the use of a cell type that
      tolerates well the environment of the immune-isolation device, while still
      delivering the therapeutic product of interest. This form of gene therapy has
      been tested in our laboratory for delivery of marker products such as human
      growth hormone to canines. As several large animal models of human genetic
      disorders are available, such as canines affected with hemophilia or the
      lysosomal storage disease mucopolysaccharidosis, testing the efficacy of immuno
      isolation for gene therapy in large animal models is an important prelude to
      human clinical trials. This review will discuss the topics outlined above, as
      well as some further considerations of the usefulness of large animal models in
      studying immune-isolation for non-autologous transplantation. Large animals may
      be more appropriate model organisms than rodents in which to study immune
      isolation, as issues such as biocompatibility and immune response in a larger
      animal can be addressed. As well, large animal studies of immune isolation may
      provide data that are more relevant than rodent studies to the eventual
      application to human clinical trials.

PMID- 9616732
TI  - Macrophysiologic roles of a delivery system for vulnerary factors needed for bone
      regeneration.
AB  - Traditional histology identifies three components of bone: cells, an
      extracellular mineralized organic matrix, and a lymphatic-vascular component.
      Specialized bone cells known as osteoblasts promote bone regeneration.
      Clinically, this property has been exploited by surgeons with autografts and bank
      bone preparations to restore deficient form and function to almost every aspect
      of the skeleton. Unfortunately, these therapies can be inadequate for patients
      with panskeletal trauma. Therefore, a suitable alternative may be a laboratory
      derived product consisting of a vulnerary factor and delivery system. The
      integration of a laboratory-engineered product in an osseous wound environment is
      a formidable challenge demanding a keen appreciation of the product's
      macrophysiologic roles in wound healing biology. Consequently, the purposes for
      this paper are 1) to define briefly macrophysiology relevant to a delivery system
      for vulnerary molecules and bone regeneration; 2) to review a key family of bone
      regenerating molecules, the bone morphogenetic proteins (BMPs); and 3) to relate
      delivery system engineering with bone regeneration.

PMID- 9616733
TI  - Use of an immunoisolation device for cell transplantation and tumor
      immunotherapy.

PMID- 9616734
TI  - Human fetal striatal transplantation in an excitotoxic lesioned model of
      Huntington's disease.

PMID- 9616735
TI  - Microcapsules as bio-organs for somatic gene therapy.
AB  - Current human gene therapy relies on genetic modification of the patient's own
      cells. An alternate non-autologous approach is to use universal cell lines
      engineered to secrete therapeutic products. Protection with immuno-isolation
      devices would allow the same recombinant cell line to be used for different
      patients, thus potentially lowering the cost of treatment. The feasibility of
      this idea has now been demonstrated in vitro and in vivo. Recombinant gene
      products with potential therapeutic applications (human growth hormone, factor
      IX, lysosomal enzymes, adenosine deaminase) have been expressed from genetically
      modified cells after encapsulation with alginate-poly-L-lysine-alginate or
      hydroxyethyl methacrylate-methyl methacrylate. We have also demonstrated the
      feasibility of this idea in vivo. After intraperitoneal implantation, genetically
      modified mouse Ltk- fibroblasts or C2C12 myoblasts encapsulated in alginate-poly
      L-lysine-alginate could deliver recombinant gene products (human growth hormone,
      human factor IX) to the systemic circulation of mice. The clinical efficacy of
      this novel approach to gene therapy has now been shown in murine models of human
      diseases. In the Snell dwarf mice deficient in growth hormone production,
      implantation of encapsulated mouse myoblasts engineered to secrete mouse growth
      hormone resulted in increases in body weight, length and organ sizes, some to >
      25% above those of the controls. In the Gus/Gus mice suffering from the lysosomal
      storage disease mucopolysaccharidosis type VII due to deficient beta
      glucuronidase, implantation of encapsulated mouse fibroblasts engineered to
      secrete mouse beta-glucuronidase resulted in delivery of normal levels of the
      enzyme in the plasma and significant correction of the organ histopathology.
      Hence, delivery of recombinant gene products through bioartificial devices
      appears to be a promising strategy for the treatment of genetic diseases.

PMID- 9616737
TI  - Alterations in G1/S cell-cycle control contributing to carcinogenesis.
AB  - Mutations involving the retinoblastoma tumor-suppressor gene (RB-1) have been
      described in a variety of human neoplasms. In addition, many tumors that retain a
      wild-type RB-1 allele harbor mutations that indirectly impair the function of the
      RB-1 gene product (pRB). pRB is a nuclear protein that regulates cell-cycle
      progression and, in at least certain tissues, differentiation. The former has
      been linked to its ability to form complexes with members of the E2F
      transcription factor family. E2F DNA-binding sites have been identified in the
      regulatory regions of a number of genes involved in cell-cycle progression. pRB
      E2F complexes actively repress transcription when bound to these sites. All tumor
      derived pRB mutants have lost the ability to bind to E2F. Conversely, activation
      of E2F-responsive genes is sufficient to overcome a pRB-induced cell-cycle block
      and, in certain cell types, can lead to transformation. Thus, E2F appears to be a
      physiologically relevant target of pRB action, and deregulation of E2F-responsive
      genes is a common, and possibly universal, step in human carcinogenesis.

PMID- 9616736
TI  - Cancer genetics in the new era of molecular biology.
AB  - The role of primary genetic factors in the etiology of cancer has become of
      intense interest to the research and clinical community. This interest has been
      heightened by recent discoveries that germ-line mutations such as BRCA1 and BRCA2
      in hereditary breast cancer are responsible for an increasing percentage of
      common solid tumors. A potpourri of proto-oncogenes and tumor-suppressor genes
      has been identified in hereditary as well as certain common sporadic and rare
      cancer types, and new cancer genes will likely be discovered every month to
      account for the 5 to 10% of the cases of cancer that can be attributed to primary
      genetic factors. Molecular mechanisms in the pathogenesis of hereditary cancer
      can result in more-targeted cancer-control measures. At least four mutator genes
      (MHS2, MLH1, PMS1 and PMS2) appear to account for 70-80% of hereditary
      nonpolypoid colorectal cancer (HNPCC). When one of these germ-line mutations is
      present in an HNPCC family, the physician is then able to determine the patient's
      lifetime cancer destiny with an accuracy of about 90% (limited only by the
      penetrance of the gene). This will enable highly targeted surveillance to be
      initiated early, such as colonoscopy beginning at ages 20 to 25 or prophylactic
      subtotal colectomy. Also, in multiple endocrine neoplasia syndromes (MEN 2A and
      2B), the identification of the culprit RET proto-oncogene now enables a secure
      diagnosis and permits testing of children who might benefit from prophylactic
      total thyroidectomy. Central to translation of these momentous molecular genetic
      discoveries into patient care is the necessity of determining who requires DNA
      testing. The cancer family history is the linchpin in making this decision.

PMID- 9616738
TI  - Breast cancer genes: therapeutic strategies.
AB  - Although effective treatments for breast cancer predated the identification of
      causative molecular defects in humans, it is widely hoped that an understanding
      and/or manipulation of the key genetic events will lead to even more effective
      therapies or even cures. Powerful methods of positional cloning and gene
      identification have identified the breast cancer genes, BRCA1 and BRCA2, which
      together are responsible for the majority of cases of hereditary breast and
      ovarian cancer. Although the BRCA1 gene is rarely mutated in sporadic breast or
      ovarian cancer, levels of BRCA1 mRNA and protein are markedly decreased in the
      majority of sporadic cases of cancer. This suggests that hereditary and sporadic
      breast cancer share common genetic themes and that treatments aimed at increasing
      levels of BRCA1 or BRCA2 may be useful for both hereditary and sporadic cancers.
      We have demonstrated that gene transfer of wild-type BRCA1 inhibits the growth of
      sporadic breast and ovarian cancer cells and suppresses growth of established
      breast and ovarian tumor models in nude mice. Mutant BRCA1 genes do not inhibit
      growth or suppress tumor, providing additional evidence that BRCA1 is a tumor
      suppressor gene. Strategies designed to increase BRCA1 expression or development
      of BRCA1-mimetic agents may be ultimately useful as therapeutic approaches.

PMID- 9616739
TI  - Predictive genetic tests: problems and pitfalls.
AB  - The role that genetic factors play in medicine has expanded, owing to such recent
      advances as those made by the Human Genome Project and the work that has spun off
      from it. The project is focusing particularly on localization and
      characterization of recognized human genetic disorders, which in turn increases
      awareness of the potential for improved treatment of these disorders. Technical
      advances in genetic testing in the absence of effective treatment has presented
      the health profession with major ethical challenges. The example of the
      identification of the BRCA1 and BRCA2 genes in families at high risk for breast
      and ovarian cancer is presented to illustrate the issues of the sensitivity of
      the method, the degree of susceptibility a positive result implies, the need for
      and availability of counseling and patient education, and confidentiality of the
      test results. A compelling need exists for adequate education about medical
      genetics to raise the "literacy" rate among health professionals.

PMID- 9616740
TI  - Hereditary predisposition to cancer.
AB  - Both hereditary and environmental factors influence the risk of cancer. Four risk
      categories, or oncodemes, can exist for a particular kind of cancer, depending
      upon the presence of neither, one, or both factors: (1) spontaneous, or
      background; (2) hereditary; (3) environmental; (4) interactive. In the second,
      mutation imparts a high relative risk, but a generally low attributable risk; in
      the fourth, the opposite obtains. The second oncodeme contains genes that are
      also important for the non-hereditary forms of the same cancer. Probably all
      forms of cancer exist in a dominantly heritable form. Most of the genes are tumor
      suppressors, although a few are oncogenes or DNA repair genes. The mutations are
      in most, if not all cases, maintained in a population by an equilibrium between
      mutation and selection. Most of the cloned genes are expressed widely among
      tissues, yet there is typically some tumor specificity. Somatic mutations in
      second alleles at the relevant loci are necessary, but generally not sufficient
      for carcinogenesis, although they, in some instances, lead to the formation of
      benign precursor lesions. Further events are necessary for carcinogenesis. This
      is particularly true for carcinomas. The benign lesions appear to involve an
      increase in number of long-lived cells that can accumulate other mutations. For
      some tumors, physiologic events, such as tissue growth at puberty or
      proliferation of embryonic stem cells, may produce this effect. Mutations of DNA
      mismatch repair genes underscore the effect that changes in somatic mutation
      rates can have, especially in the risk for multi-event carcinomas. Conversely,
      these are the tumors that offer the greatest opportunity for prevention.

PMID- 9616741
TI  - Nutrition and human cancer.
AB  - It is now widely accepted that nutrition is as important as tobacco as a cause of
      human cancer. However, whereas we can dispense with tobacco with general benefit
      to health, we cannot do without food. It is, therefore, necessary to determine
      the pattern of nutrition that is associated with the lowest overall cancer risk.
      This is made more difficult by the fact that some kinds of cancer are associated
      with overnutrition (e.g., that of the colon, breast, and prostate) and some with
      poor nutrition (e.g., esophagus, stomach, and liver). The tools to determine this
      are epidemiology, animal models, in vitro studies, and dietary intervention
      studies. These all have their strengths and weaknesses, which will be discussed.
      It is concluded that the major nutrition factors associated with increased cancer
      risk are: (a) overweight [as a surrogate for excess energy intake]; (b) low
      intake of fresh fruit; (c) low intake intake of vegetables; and (d) low intake of
      whole-grain cereals. There have been many other associations with cancer at
      specific sites noted in the literature. However, it is the overall risk of cancer
      that must be minimized.

PMID- 9616742
TI  - The epidemiology of physical activity and cancer.
AB  - Experimental studies in animals and epidemiological studies in human populations
      support an inverse association between exercise and the development of cancer.
      Physical activity has been shown to be protective against the development of
      breast and colon cancer and may also be important for other kinds of cancer such
      as that of the prostate. The proposed biological mechanisms for the physical
      activity--cancer association include exercise's effect on immune function,
      transit time of digestion, hormones, and body fat. There has been little research
      on physical activity and the effect on progression of cancer, although there are
      studies to suggest that it may slow the clinical course of the disease.
      Furthermore, exercise may be beneficial in the treatment of cancer through mood
      elevation, decreased loss of lean tissue, and increased quality of life. Much is
      still to be learned about the effect of exercise on cancer. The intensity,
      duration, frequency, and type of exercise that is relevant need to be clarified.
      As well, the time period during life when exercise is important has not been
      determined. It seems reasonable to conclude that exercise, a modifiable risk
      factor, is beneficial in preventing certain forms of cancer. Public health
      interventions may hold promise for cancer prevention.

PMID- 9616743
TI  - Tobacco and cancer: approaches using carcinogen biomarkers and chemoprevention.
AB  - Tobacco products are the leading cause of avoidable cancer death in the U.S.,
      accounting for approximately 30% of all cancer deaths. While avoidance of tobacco
      and smoking cessation are clearly the best way to decrease tobacco-related
      cancer, these approaches have not been uniformly successful. Approximately 25% of
      the U.S. population over 18 years of age smokes cigarettes, while 6% use
      smokeless tobacco products; these figures have not changed markedly in recent
      years. Our approach toward the tobacco and cancer problem is based on an
      understanding of the carcinogens in tobacco smoke. These carcinogens form the
      link between nicotine addiction and cancer. In this paper, two strategies for
      cancer prevention--the development of carcinogen-derived biomarkers and
      chemopreventive agents--are discussed. Carcinogen-derived biomarkers can provide
      specific information on individual metabolic activation and detoxification of
      tobacco carcinogens. This information can be used to assess individual risk for
      cancer development upon exposure to tobacco products. Chemopreventive agents can
      be targeted against the important carcinogens in tobacco smoke. Isothiocyanates,
      strong inhibitors of lung cancer development by the tobacco-specific nitrosamine
      4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, are discussed as an example of
      this approach.

PMID- 9616744
TI  - Avoidable causes of breast cancer: the known, unknown, and the suspected.

PMID- 9616745
TI  - Hormone replacement therapy increases the risk of breast cancer.
AB  - Established risk factors for breast cancer predominantly act through hormonal
      pathways. The major exceptions are (1) family history, which accounts for
      approximately 6 percent of the cases of breast cancer in the United States, (2)
      radiation, particularly in adolescence, which accounts for a small fraction of
      all cases of breast cancer, and (3) personal history of benign breast disease,
      which may include precursor lesions in the pathway to breast cancer. Age at
      menarche, parity, and age at first birth, as well as age at menopause are related
      to risk of breast cancer. In addition, among postmenopausal women, relative
      weight and use of postmenopausal hormones increase risk of breast cancer. This
      paper reviews the evidence that these factors may act through hormonal pathways
      or cell division in response to cyclic hormonal levels.

PMID- 9616746
TI  - The war on cancer: a review.
AB  - Twenty-five years ago, then President Nixon "declared war" on cancer. In this
      personal commentary, the war is reviewed. There have been obvious triumphs, for
      instance in cure of acute lymphocytic leukemia and other forms of childhood
      cancer, Hodgkin's disease, and testicular cancer. However, substantial advances
      in molecular oncology have yet to impinge on mortality statistics. Too many
      adults still die from common epithelial cancers. Failure to appreciate that local
      invasion and distant metastasis rather then cell proliferation itself are lethal,
      obsession with cure of advanced disease rather than prevention of early disease,
      and neglect of the need to arrest preneoplastic lesions, may all have served to
      make victory elusive.

PMID- 9616747
TI  - Computer-assisted molecular design for the determination of structure-activity
      relationships for chemopreventive agents.

PMID- 9616748
TI  - Physician- and counselor-tailored hybrid computer interfaces for cancer genetics
      risk analysis software.
AB  - During development of the Strang Breast Cancer Risk Evaluator, different computer
      interfaces were designed, implemented and tested for useability by physicians and
      genetics counselors during a counseling session. The current BCRE 2.3 implements
      a hybrid interface, combining modern GUI (graphical user interface) windows,
      buttons, and menus with a linear, sequence-of-operations chronological
      progression reminiscent of interfaces prior to the GUI revolution. Although such
      hybrids are considered by many interface specialists inappropriate to modern
      broad-spectrum computer applications, vertical market applications, including
      this one, can capitalize on such hybridization effectively. The hybrid interface
      provides multiple visual cues and directions to the user as to the next
      appropriate action, thereby allowing a physician or counselor to concentrate
      his/her attention on the patient, returning his/her gaze to the screen at
      sporadic and widely spaced moments. Hybrid interfaces combine specific interface
      elements--such as triple-scale checkboxes, text and design metaphors, "next step"
      helper icons, color-coded content, and color and graphically tailored on-screen
      reports (all of which constitute GUI elements)--with a strictly linear data
      accrual, approval, calculation, storage and reporting progression (which sequence
      constitutes a pre-GUI interface design). A first-generation design is presented:
      a hybrid combining the visual efficiency of GUI-improved interfaces with the
      practical efficiencies of stream-lined and linear progressions.

PMID- 9616749
TI  - Genetic object class networks: transformational object modeling of breast cancer
      risk and family history data.

PMID- 9616750
TI  - Ethical aspects of genetic counseling in familial breast and ovarian cancer.
      Combining applied theory and reflective practice.

PMID- 9616751
TI  - Phorbol ester-mediated induction of cyclooxygenase-2 gene expression is inhibited
      by retinoids.

PMID- 9616752
TI  - Cyclooxygenase-2 gene expression is upregulated in transformed mammary epithelial
      cells.

PMID- 9616753
TI  - Mutation of alpha-catenin results in invasiveness of human HCT-8 colon cancer
      cells.

PMID- 9616754
TI  - Design and methodology of a study of psychosocial aspects of genetic testing for
      hereditary colorectal cancer.

PMID- 9616755
TI  - BRCA1/BRCA2 mutations and breast cancer in Ashkenazi Jewish women.

PMID- 9616757
TI  - Gene therapy for nervous system disease.

PMID- 9616756
TI  - Effect of Maitake D-fraction on cancer prevention.

PMID- 9616758
TI  - Trophic factors, synaptic plasticity, and memory.

PMID- 9616759
TI  - Findings about the cholinergic basal forebrain using immunotoxin to the nerve
      growth factor receptor.

PMID- 9616760
TI  - Neural precursors and neuronal production in the adult mammalian forebrain.

PMID- 9616761
TI  - Central regulation of sympathetic ganglia development: heterogeneous response of
      paravertebral, prevertebral, and terminal ganglia.
AB  - These studies expand previous observations regarding the central control of
      neuronal maturation and indicate that paravertebral, prevertebral, and terminal
      ganglia are all under central influences, but in varying degrees. These
      variations are probably related to the relative contributions that central
      pathways exert on specific peripheral neuronal populations during growth and
      development as well as the various roles of more peripheral developmental
      modulators such as target organs and hormones, especially in the case of the HG.
      It is apparent, therefore, that during development central injury may result in
      heterogeneous deficits depending on the unique intrinsic and extrinsic
      environment that each ganglion population shares.

PMID- 9616762
TI  - Sodium channel regulation of skeletal muscle membrane excitability.

PMID- 9616763
TI  - The effectiveness of distal synaptic inputs on neurons.

PMID- 9616764
TI  - Paraneoplastic syndromes: a brief review.

PMID- 9616765
TI  - Immune responses and dementia.

PMID- 9616766
TI  - Autoimmune neuromyotonia (Isaacs' syndrome): an antibody-mediated potassium
      channelopathy.

PMID- 9616768
TI  - Management of primary brain tumors--1996.

PMID- 9616767
TI  - Oral administration of myelin induces antigen-specific TGF-beta 1 secreting T
      cells in patients with multiple sclerosis.
AB  - Oral administration of antigen is a long-recognized method of inducing systemic
      immune tolerance. In animals with experimental autoimmune disease, a major
      mechanism of oral tolerance involves the induction of regulatory T cells that
      mediate active suppression by secreting the cytokine TGF-beta 1. Multiple
      sclerosis (MS) is a presumed T cell-mediated Th1 type autoimmune disease. In this
      paper we investigated, in patients with MS, whether oral myelin treatment (myelin
      containing both MBP and PLP) induced antigen-specific MBP- or PLP-reactive T
      cells that were either Th2-like (secreted IL-4 or TGF-beta 1), or alternatively
      whether Th1 type sensitization occurred as measured by IFN-gamma secretion.
      Specifically, 4,860 short-term T cell lines were generated to either MBP, PLP or
      TT from 34 relapsing-remitting patients with MS; 17 were orally treated with
      bovine myelin daily for a minimum of two years as compared to 17 non-treated
      patients. We found a marked increase in the relative frequencies of both MBP- and
      PLP-specific TGF-beta 1 secreting T cell lines in the myelin-treated MS patients
      as compared to non-treated MS patients (MBP, p < 0.001; PLP, p < 0.003). In
      contrast, no changes in the frequency of MBP- or PLP-specific IFN-gamma or TT
      specific TGF-beta 1 secreting T cells were observed. These results suggest that
      the oral administration of antigens generates antigen-specific TGF-beta 1
      secreting T cells of presumed mucosal origin that may represent a distinct
      cytokine-secreting lineage of T cells (Th3). Since, in animal models, antigen
      specific TGF-beta 1 secreting cells localize to the target organ and then
      suppress inflammation in the local microenvironment, oral tolerization with self
      antigens may provide a therapeutic approach for the treatment of cell-mediated
      autoimmune disease which does not depend upon knowledge of the antigen
      specificity of the original T cell clone triggering the autoimmune cascade.

PMID- 9616769
TI  - Cellular and humoral immune responses associated with HTLV-I associated
      myelopathy/tropical spastic paraparesis.

PMID- 9616770
TI  - Functional anatomical and behavioral consequences of dopamine receptor
      stimulation.
AB  - Taken together with electrophysiological data, these results suggest that in
      states of DA deficiency, systemically administered L-dopa or DA agonist drugs
      inhibit cell firing in the major output nuclei of the basal ganglia (GPI and
      SNPR). We propose that DA produces this net effect by a direct influence on the
      striato-GPI and striato-SNPR neurons, as well as indirectly via the striato-GPE
      STN-GPI/SNPR circuit. The RCGU data suggest that DA activates the direct pathway
      by stimulating D1 receptor-bearing striatal GABAergic neurons projecting to GPI
      and SNPR. Supportive evidence includes the ability of D1 agonists to facilitate
      GABA release in the striatum and to increase the firing rates of striatonigral
      neurons. The RCGU data also support a net stimulatory action of DA on the GPE
      output on STN, consistent with the excitatory effects of DA on GPE neuronal
      firing rates. This effect may be mediated by both D1 and D2 receptors.
      Stimulation of this pathway should physiologically inhibit the STN resulting in
      dysfacilitation of the GPI and SNPR. According to this scheme, DA exerts
      complementary actions via both direct and indirect anatomical pathways to
      decrease tonic firing rates of intrinsic neurons in the major output nuclei of
      the basal ganglia (i.e., GPI and SNPR).

PMID- 9616771
TI  - Heat shock or stress proteins and their role as autoantigens in multiple
      sclerosis.
AB  - Stress or heat shock proteins are constitutively expressed in normal CNS tissues,
      in a variety of cell types (oligodendrocytes, astrocytes, and neurons). Their
      presence may protect cells from various stresses, such as hypoxia, anoxia, and
      excessive excitatory stimulation. Increased amounts of hsp are expressed in
      various cells of the CNS during acute toxic-metabolic states and in chronic
      degenerative and inflammatory diseases. Increased expression of hsp may lead to
      immune responses to these proteins. Antibodies to mycobacterial hsp bind to
      normal human myelin and to oligodendrocytes in regions of MS demyelination.
      Cellular immune responses to hsp occur with increased frequency and magnitude in
      persons with MS, especially those with recent onset of disease. In addition,
      there are populations of T cells expressing gamma/delta antigen receptors in the
      brains and spinal fluids of persons with MS, suggesting an in situ immune
      response to hsp. Humoral immune responses to hsp are found in CSF, but no disease
      specificity has been documented. Some myelin proteins have sequence homology with
      particular hsp. One instance is the homology between a peptide of mycobacterial
      HSP 65 and the myelin protein CNP. Our data in EAE suggest that immune responses
      to either cross-reactive epitopes or whole hsp can modify the course of both
      acute and chronic relapsing EAE. These data support the hypothesis that an immune
      response to an infectious agent's hsp could result in a cross-reactive immune
      response to CNS myelin, or to responses to endogenous, CNS-expressed hsp,
      resulting in demyelination. This may be an important mechanism in the
      pathogenesis of MS.

PMID- 9616772
TI  - Central neurogenic neuroprotection: central neural systems that protect the brain
      from hypoxia and ischemia.
AB  - The brain can protect itself from ischemia and/or hypoxia by two distinct
      mechanisms which probably involve two separate systems of neurons in the CNS.
      One, which mediates a reflexive neurogenic neuroprotection, emanates from oxygen
      sensitive sympathoexcitatory reticulospinal neurons of the RVLM. These cells,
      excited within seconds by reduction in blood flow or oxygen, initiate the
      systemic vascular components of the oxygen conserving (diving) reflex. They
      profoundly increase rCBF without changing rCGU and, hence, rapidly and
      efficiently provide the brain with oxygen. Upon cessation of the stimulus the
      systemic and cerebrovascular adjustments return to normal. The system mediating
      reflex protection projects via as-yet-undefined projections from RVLM to upper
      brainstem and/or thalamus to engage a small population of neurons in the cortex
      which appear to be dedicated to transducing a neuronal signal into vasodilation.
      It also appears to relay the central neurogenic vasodilation elicited from other
      brain regions, including excitation of axons innervating the FN. This mode of
      protection would be initiated under conditions of global ischemia and/or
      hypoxemia because the signal is detected by medullary neurons. The second
      neuroprotective system is represented in intrinsic neurons of the cerebellar FN
      and mediates a conditioned central neurogenic neuroprotection. The response can
      be initiated by excitation of intrinsic neurons of the FN and does not appear
      dependent upon RVLM. The pathways and transmitters that mediate the effect are
      unknown. The neuroprotection afforded by this network is long-lasting, persisting
      for almost two weeks, and is associated with reduced excitability of cortical
      neurons and reduced immunoreactivity of cerebral microvessels. This mode of
      neuroprotection, moreover, is not restricted to focal ischemia, as we have
      demonstrated that it also protects the brain against global ischemia and
      excitotoxic cell death. That the brain may have neuronal systems dedicated to
      protecting itself from injury, at first appearing to be a novel concept, is, upon
      reflection, not surprising since the brain is not injured in naturalistic
      behaviors characterized by very low levels of rCBF, diving and hibernation. An
      understanding of the pathways, transmitters, and molecules engaged in such
      protection may provide new insights into novel therapies for a range of disorders
      characterized by neuronal death.

PMID- 9616773
TI  - Ischemic brain injury and the therapeutic window.

PMID- 9616774
TI  - Whole-body hyperthermia and ADPRT inhibition in experimental treatment of brain
      tumors.
AB  - Malignant primary brain tumors have hitherto been incurable. One reason for this
      may be the migrating tumor cells that spread into the surrounding normal brain,
      creating the basis for inevitable recurrences. Therefore, local therapy may have
      a temporary effect, but for a cure, the treatment must reach all the tumor cells.
      Whole-body hyperthermia (WBH) is such a general treatment, which we have studied
      in a rat glioma model. Cells of the RG2 rat glioma cell line were inoculated in
      the right caudate nucleus of Fischer-344 rats, which were then either controls or
      treated with WBH, induced by a radiant heat device for 4-5 sessions of 30 min at
      body temperature 42 degrees C (rectal), and/or nicotinamide (NAM), an effective
      radiosensitizer in animal tumor models and an inhibitor of ADPRT (poly adenosine
      diphosphate ribosyl transferase), a chromatin-bound enzyme suggested to be
      important in the DNA repair system. We have shown that WBH 42 degrees C alone, or
      in combination with NAM, has no effect upon tumor growth if a larger number of
      RG2 cells (5,000) are inoculated. If only 1,000 cells are inoculated, a
      significant inhibitory effect (p < 0.05) is observed on tumor growth as compared
      to the untreated control animals. Thus, WBH is feasible, and in some
      circumstances effective, in a rat glioma model. WBH in combination with other
      therapies influencing cell metabolism may be of value in future postoperative
      treatment of human malignant brain tumors.

PMID- 9616776
TI  - Ketogenic diet and the brain.

PMID- 9616775
TI  - Molecular pathology of cerebral ischemia: delayed gene expression and strategies
      for neuroprotection.
AB  - The evidence reviewed in this paper suggests that molecular and cellular events
      occurring in the late stages of cerebral ischemia (> 6 h) play an important role
      in the evolution of ischemic brain damage. We focused our inquiry on two
      inflammation-related genes iNOS and COX-2. iNOS is expressed in inflammatory and
      vascular cells in the post-ischemic brain. Pharmacological inhibition of iNOS
      activity ameliorates ischemic damage, whereas knockout mice lacking the iNOS gene
      are relatively protected from the consequences of cerebral ischemia. COX-2 is
      expressed in neurons at the infarct border and inhibition of COX-2 activity
      improves ischemic brain damage. These results indicate that expression of iNOS
      and COX-2 contributes to the late stages of ischemic brain damage. Consequently,
      inhibition of iNOS and COX-2 could be a valuable addition to treatment strategies
      for ischemic stroke. Most efforts to date have targeted the acute phase of
      cerebral ischemia. Inhibition of iNOS or COX-2 offers the prospect of treatments
      directed to the late stages of the damage. However, additional preclinical
      studies would be necessary before these new treatment strategies can be tested in
      human stroke.

PMID- 9616777
TI  - Nitroxidergic transmission in the nucleus tractus solitarii.

PMID- 9616778
TI  - A model of perinatal hypoxic-ischemic brain damage.
AB  - In conclusion, our immature rat model has gained wide acceptance as the animal
      model of choice to study basic physiologic, biochemical, and molecular mechanisms
      of perinatal hypoxic-ischemic brain damage. In addition, the model has been used
      extensively to study those physiologic and therapeutic variables which either are
      deleterious or beneficial to the perinatal brain undergoing hypoxia-ischemia. As
      therapeutic interventions are tested in the animal setting, the results will
      provide important information regarding the effect of these agents in the human
      setting.

PMID- 9616779
TI  - Red and white brain.

PMID- 9616780
TI  - Neuronal survival: cellular and molecular pathways of protection.

PMID- 9616781
TI  - On the rate of decarboxylation of dopa to dopamine in living mammalian brain.

PMID- 9616782
TI  - Role of apoptotic proteins in ischemic hippocampal damage.
AB  - In this review, we have presented evidence that apoptotic proteins may be
      involved in ischemic cell death. We tried to keep in mind that focal and global
      ischemia almost certainly produces different forms of cell death. For example,
      necrotic cell death is clearly part of a focal cerebral infarct, although it is
      not seen in brief global insults. We also tried to make the point that not all
      apoptosis is the same and that various forms of non-necrotic cell death,
      including ischemic cell death after global ischemia, may share some of the same
      molecular mechanisms as classic forms of apoptosis. Finally, we wish to leave the
      reader with the clear impression that all the evidence is not in hand. More work
      needs to be done in animals to define the role of apoptotic proteins. For
      example, glial cells probably are important in necrosis and may play a role in
      ischemic cell death after transient global ischemia. Yet it is likely that glial
      cells die from injury in a different manner than neurons. A better understanding
      of these processes should lead to new therapeutic approaches that may make
      possible the salvaging of neurons well after an ischemic insult.

PMID- 9616783
TI  - Neurological aspects of the conscious and unconscious mind.

PMID- 9616784
TI  - Sensory coding in cortical neurons. Recent results and speculations.
AB  - We described a novel approach to the study of how spike trains encode sensory
      information. This approach emphasizes the idea that spike trains are sequences of
      discrete events, rather than approximations to continuous signals. Aided by some
      simple heuristics, such as a caricature of neurons as coincidence detectors, we
      constructed candidate notions of "distances" between spike trains, considered as
      points in an abstract space. Each candidate distance was evaluated for relevance
      to biological encoding by determining whether it led to systematic, stimulus
      dependent, clustering of the neural responses. We showed here that these distance
      can also be used to construct a "response space" for the neuron. The response
      space, which is typically not Euclidean, can represent two or three stimulus
      attributes. We also introduced the notion of a "consensus spike train," defined
      as the spike train with minimum average distance from a set of observed
      responses. For the distances we considered, the consensus spike train (for a
      particular stimulus) contained only those spikes that were present at consistent
      times across the observed responses to that stimulus, and thus contained fewer
      spikes than the typical observed responses. Nevertheless, these consensus spike
      trains provided an equivalent (or even superior) representation of the stimulus
      array.

PMID- 9616785
TI  - Transforming sensory perceptions into motor commands: evidence from programming
      of eye movements.
AB  - The visual stimulus for a saccadic eye movement is encoded in place-coded maps in
      cerebral cortex and the dorsal superior colliculus. In contrast, the motor
      command for the saccade is encoded by the temporal discharge properties of ocular
      motoneurons and premotor burst neurons in the brain-stem reticular formation.
      Thus, there is need for a spatial-temporal transformation of neural signals, and
      recent findings suggest that the superior colliculus might contribute to this
      process. The ventral, output layers of the superior colliculus encode the metric
      of the desired saccade in polar coordinates. However, premotor neurons in the
      pontine and mesencephalic reticular formation are organized to generate
      horizontal and vertical saccades, respectively. Studies of oblique saccades in
      patients with slow vertical components--due to Niemann-Pick type C disease-
      support the interpretation that the saccadic command from the reticular formation
      is encoded in Cartesian coordinates. Currently, saccades are thought to be
      generated under local, brain-stem feedback control in which current eye
      displacement is continuously subtracted from desired eye displacement to compute
      motor error--the remaining movement required for the eye to acquire the target.
      If the superior colliculus is positioned in the feedback loop, then there is a
      need for transformation of premotor signals back into a place-coded version of
      motor error. Recent studies suggest that, during the saccade, this might be
      achieved by a wave of activity spreading rostrally, which traverses the
      collicular map in a direction corresponding to progressively smaller movements
      and finally activates a group of neurons concerned with fixation. These new
      hypotheses are ripe for testing by basic and clinical studies. By confronting the
      issue of what signal transformations are required to program visually guided
      saccades, new experimental approaches have emerged. Such computational approaches
      offer insights into how the brain controls behavior not just by measuring
      stimulus and response, but by asking what "currency" is being used by interacting
      populations of neurons at any stage in the process.

PMID- 9616786
TI  - A pivotal role of nitric oxide in migraine pain.

PMID- 9616787
TI  - Food for thought. The metabolic and circulatory requirements of cognition.

PMID- 9616788
TI  - The persistent vegetative state: a view across the legal divide.

PMID- 9616789
TI  - Emerging concepts in sports neurology.

PMID- 9616790
TI  - Symptom localization in neuropsychiatry. A functional neuroimaging approach.

PMID- 9616791
TI  - Suicide research. Overview and introduction.

PMID- 9616792
TI  - The behavioral neurobiology of self-injurious behavior in rhesus monkeys. Current
      concepts and relations to impulsive behavior in humans.
AB  - The objective of this report is to critically review past reports and present new
      data on the psychobiology of self-injurious behavior (SIB) and/or "risky" or
      "impulsive" behavior in primates (human and nonhuman). One aim was to reexamine
      how early social deprivation and neurobiological changes caused by deprivation
      might contribute to SIB in monkeys, and how the causes of SIB in monkeys might
      inform us about the psychobiology of suicide in humans. A second aim was to
      examine the evidence that social deprivation in monkeys produces reductions in
      brain 5-HT system function that are causal or coincident factors associated with
      self-injurious or impulsive behavior. Prior studies and new data indicate that
      the environmental causes of SIB and unusual aggression in rhesus monkeys do not
      produce reductions in brain 5-HT system activity and that experimental production
      of low levels of brain 5-HT system activity does not reliably promote either SIB
      or unusual other-directed aggression in monkeys. A third and final aim was to
      suggest that in severe cases of environmentally induced SIB and/or aggression in
      monkeys, having relatively high or low levels of 5-HT system activity may not be
      related to ongoing behavior because the 5-HT system may not interact with other
      neurotransmitter systems in the usual way. Overall, the contention is that
      primates exhibiting SIB and unusual aggression may have altered 5-HT system
      function, but this may be but one aspect of a more profound disorganization of
      brain function involving many neurohormonal and transmitter systems. Contemporary
      theorizing and experimentation tends to be restricted to the idea that altered
      function in one key system might be the cause of a specific form of
      psychopathology. In the future, research examining the probable change
      interactions of neurotransmitter and neuroendocrine systems as underlying causes
      of behavioral disorders should have a high priority.

PMID- 9616793
TI  - Low central nervous system serotonergic activity is traitlike and correlates with
      impulsive behavior. A nonhuman primate model investigating genetic and
      environmental influences on neurotransmission.
AB  - We have used nonhuman primates to examine developmental and behavioral correlates
      of CNS serotonergic activity, as measured by concentrations of the serotonin
      metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF).
      These studies show that interindividual differences in CNS serotonin turnover
      rate exhibit traitlike qualities and are stable across time and settings, with
      interindividual differences in CSF 5-HIAA concentrations showing positive
      correlations across repeated sampling. Primates with low CNS serotonergic
      activity exhibit behaviors indicative of impaired impulse control, unrestrained
      aggression, social isolation, and low social dominance. Maternal and paternal
      genetic influences play major roles in producing low CNS serotonin functioning,
      beginning early in life. These genetic influences on serotonin functioning are
      further influenced by early rearing experiences, particularly parental
      deprivation.

PMID- 9616794
TI  - Assessing the observed relationship between low cholesterol and violence-related
      mortality. Implications for suicide risk.
AB  - Health advocacy groups advise all Americans to restrict their dietary intake of
      saturated fat and cholesterol as an efficacious and safe way to lower plasma
      cholesterol concentrations and thus reduce the risk of coronary heart disease and
      other atherosclerotic disorders. However, accumulating evidence suggests that
      naturally low or clinically reduced cholesterol is associated with increased
      nonillness mortality (principally suicide and accidents). Other evidence suggests
      that such increases in suicide and traumatic death may be mediated by the adverse
      changes in behavior and mood that sometimes accompany low or reduced cholesterol.
      These observations provided the rationale for an ongoing series of studies in
      monkeys designed to explore the hypothesis that alterations in dietary or plasma
      cholesterol influence behavior and that such effects are potentiated by lipid
      induced changes in brain chemistry. In fact, the investigations in monkeys reveal
      that reductions in plasma cholesterol increase the tendency to engage in
      impulsive or violent behavior through a mechanism involving central serotonergic
      activity. It is speculated that the cholesterol-serotonin-behavior association
      represents a mechanism evolved to increase hunting or competitive foraging
      behavior in the face of nutritional threats signaled by a decline in total serum
      cholesterol (TC). The epidemiological and experimental data could be interpreted
      as having two implications for public health: (1) low-cholesterol may be a marker
      for risk of suicide or traumatic death and (2) cholesterol lowering may have
      adverse effects for some individuals under some circumstances.

PMID- 9616795
TI  - Insights into the neurobiology of impulsive behavior from serotonin receptor
      knockout mice.
AB  - Although the concept of impulsivity has proved useful in human and animal studies
      of addiction, violent aggression, and violent suicide, and has been recognized as
      an important component of human behavior, little research has been done to
      understand the underlying psychobiological mechanisms. We explore the concept of
      impulsivity and its relation with the neurotransmitter serotonin in the context
      of aggressive behavior and behavior associated with positive reinforcement using
      a knockout mouse that lacks one of the serotonin receptors, the 5-HT1B receptor.
      This knockout mouse shows more impulsive aggression, acquires cocaine self
      administration faster, and drinks more alcohol than the corresponding wild-type
      control. We show that the impulsive characteristics of these mice are not due to
      change in cognitive functions: in a cognitive task involving a choice between a
      small immediate one and a larger more delayed reward, knockout mice showed intact
      choice and timing capabilities and good discrimination of reward amounts. Thus,
      this mouse may prove an animal model of addiction and motor impulsivity.

PMID- 9616796
TI  - Regulation of 5-HT receptors and the hypothalamic-pituitary-adrenal axis.
      Implications for the neurobiology of suicide.
AB  - Disturbances in the serotonin (5-HT) system is the neurobiological abnormality
      most consistently associated with suicide. Hyperactivity of the hypothalamic
      pituitary-adrenal (HPA) axis is also described in suicide victims. The HPA axis
      is the classical neuroendocrine system that responds to stress and whose final
      product, corticosteroids, targets components of the limbic system, particularly
      the hippocampus. We will review results from animal studies that point to the
      possibility that many of the 5-HT receptor changes observed in suicide brains may
      be a result of, or may be worsened by, the HPA overactivity that may be present
      in some suicide victims. The results of these studies can be summarized as
      follows: (1) chronic unpredictable stress produces high corticosteroid levels in
      rats; (2) chronic stress also results in changes in specific 5-HT receptors
      (increases in cortical 5-HT2A and decreases in hipocampal 5-HT1A and 5-HT1B); (3)
      chronic antidepressant administration prevents many of the 5-HT receptor changes
      observed after stress; and (4) chronic antidepressant administration reverses the
      overactivity of the HPA axis. If indeed 5-HT receptors have a partial role in
      controlling affective states, then their modulation by corticosteroids provides a
      potential mechanism by which these hormones may regulate mood. These data may
      also provide a biological understanding of how stressful events may increase the
      risk for suicide in vulnerable individuals and may help us elucidate the
      neurobiological underpinnings of treatment resistance.

PMID- 9616797
TI  - Genetics of suicides. Family studies and molecular genetics.
AB  - Suicidal behavior, like so much else in psychiatry, tends to cluster in families.
      Clinical studies show that a family history of suicide is associated with a
      raised risk of both attempts at suicide and completed suicide. Twin studies show
      that monozygotic twins have a greater concordance for suicidal behavior than
      dizygotic twins. Adoption studies also suggest that there may be genetic factors
      in suicide. Most recently, molecular genetic studies report that polymorphisms of
      the tryptophan hydroxylase gene are associated with suicidal behavior.

PMID- 9616798
TI  - Neurotransmitters and suicidal behavior. The evidence from cerebrospinal fluid
      studies.
AB  - Studies of neurotransmitter metabolites in cerebrospinal fluid (CSF) were
      initially focused on depressive illness. Although several studies have
      demonstrated low concentrations of the serotonin metabolite, 5
      hydroxyindoleacetic acid (5-HIAA), and the dopamine metabolite, homovanillic acid
      (HVA), in depressed patients, these early studies may have been biased by
      concomitant administration of antidepressant drugs (which tend to lower CSF 5
      HIAA), amount of CSF drawn (there is a concentration gradient for both
      metabolites), and selection of control subjects. Once these methodological
      details are controlled for, the differences between depressed patients and
      controls are unimpressive. However, there is a remarkably consistent association
      between low concentrations of CSF 5-HIAA and suicidal behavior, as evidenced by
      over 20 studies. The association is not confined to depressive illness but has
      also been found in schizophrenia, personality disorder, and certain impulse
      control disorders (but, interestingly, not in bipolar disorder). A low
      concentration of CSF 5-HIAA in a suicide attempter is associated with a
      substantial increase in short-term suicide risk. CSF studies in violent
      criminals, and in nonhuman primates, suggest that aggression dyscontrol may
      partly explain the association between suicide and serotonin, which is of
      considerable theoretical interest. CSF 5-HIAA determinations may also be helpful
      in the clinical assessment of suicide risk.

PMID- 9616799
TI  - Altered serotonin function in suicide. Evidence from platelet and neuroendocrine
      studies.
AB  - Significant progress has been made in understanding psychosocial, psychological,
      and environmental factors associated with suicide; however, it is only recently
      that attention has been paid to the understanding of the neurobiology of suicide.
      There are several studies that implicate the serotonin (5-HT) system in suicide.
      Initial evidence was obtained from observations of low 5-hydroxyindoleacetic acid
      (5-HIAA) in cerebrospinal fluid (CSF) of depressed patients with a previous
      history of suicide attempts. Several strategies have been used to examine the
      serotonergic system in suicidal behavior, which include the determination of
      serotonin and its metabolites in CSF and postmortem brain tissues as well as
      serotonin receptor subtypes in postmortem brain tissues, and in platelets of
      suicidal patients. The neuroendocrine strategy, often termed the "window to the
      brain," has been extensively used for studying the serotonergic system in
      suicide. This chapter will review the results obtained from neuroendocrine and
      serotonin studies in platelets. Initial studies in platelets focussed on
      determining serotonin uptake and serotonin transporter binding sites in platelets
      of depressed and suicidal patients. Whereas several studies have found decreased
      imipramine binding sites of platelets of depressed patients, imipramine binding
      sites in platelets of suicidal patients showed inconsistent results. Similarly,
      no consistent changes in 5-HT uptake have been observed in platelets obtained
      from suicidal patients compared to nonsuicidal patients. On the other hand,
      studies of platelet 5-HT2A receptors appear to be quite encouraging. Initially,
      several investigators indicated that they found an increase in platelet 5-HT2A
      receptors in depressed patients. Subsequently, it was shown that platelet 5-HT2A
      receptors in suicidally depressed patients were significantly higher compared to
      nonsuicidally depressed patients and normal control subjects. It has also been
      shown that platelet 5-HT2A receptors are increased in suicidal patients
      independent of diagnosis, similar to platelets. 5-HT2A receptors have also been
      shown to be increased in the postmortem brain of suicide victims by several
      investigators, although some investigators do not find such an increase. The
      neuroendocrine strategy provides an important method for studying serotonin
      function in the central nervous system of depressed and suicidal patents. Using a
      serotonergic probe of 5-HT1A receptors, several investigators examined ipsapirone
      induced prolactin release in suicidal patients and did not find it different that
      that of control subjects. On the other hand, fenfluramine, which causes release
      of serotonin and blocks serotonin uptake, causes a decreased release of prolactin
      in depressed patients compared to normal control subjects. Furthermore it has
      been shown by some investigators that fenfluramine-induced prolactin release is
      also decreased in suicidal patients compared to normal control subjects. In
      summary, platelet and neuroendocrine studies have provided initial evidence
      sufficient to suggest serotonergic abnormalities in suicidal patients. Most
      earlier evidence is based on CSF 5-HIAA studies, but it appears that 5-HT2A
      receptors in both platelet and postmortem brain samples are increased in suicidal
      patients. The observation that platelet 5-HT2A receptors are increased in
      suicidal patients independent of diagnosis provides a very useful potential
      biological marker for identifying suicidal patients.

PMID- 9616800
TI  - Neuropathology of suicide. A review and an approach.
AB  - Neuropathology is one approach to the effort to elucidate the pathophysiology of
      suicide. Initial neurochemical studies focusing on the roles of serotonin (5-HT)
      and noradrenaline (NE) abnormalities in brains of suicide victims have been
      somewhat inconsistent. More recently developed methodologies, including
      quantitative receptor autoradiography, immunoblotting, immunohistochemistry, cell
      morphometry, in situ hybridization, Northern analysis, solution
      hybridization/RNase protection assay, reverse transcriptase polymerase chain
      reaction, and genotyping, which have already been applied successfully in studies
      of other disorders of brain structure or function, are now increasingly being
      adopted for postmortem studies of suicide. These new strategies are adding
      convergent evidence for brain 5-HT and NE dysfunction in the etiology of suicide
      susceptibility, refining the neuroanatomical localization of this dysfunction,
      and in addition, implicating heretofore unsuspected candidate neurotransmitter
      systems in the neuropathological substrates of suicide susceptibility. It is
      argued here that the confluence of the availability of suitable postmortem
      samples and this augmentation of our armamentarium of techniques promises the
      attainment of important new insights into the biological underpinnings of suicide
      from postmortem research. It is to be hoped that this new knowledge might inspire
      novel pharmacotherapeutic strategies for the prevention of suicide.

PMID- 9616801
TI  - Neurobiology of serotonin in depression and suicide.
AB  - Alterations in serotonin neurotransmission have been implicated in the
      pathophysiology of major depression and suicide. However, a clear picture of
      serotonergic abnormalities has not emerged from postmortem studies of depression
      and suicide. In suicide victims with major depression and psychiatrically normal
      control subjects, we have examined various indices of serotonergic
      neurotransmission in axonal projection areas such as prefrontal cortex and
      hippocampus, and cell bodies of origin within the dorsal raphe nucleus (DR).
      Although there were no significant differences between suicide victims with major
      depression and psychiatrically normal control subjects in serotonin-1A or
      serotonin-2A receptors in the right prefrontal cortex (area 10) or the
      hippocampus, there were region-specific alterations in suicide victims with major
      depression in G-protein-induced activation of the phosphoinositide signal
      transduction system and in the levels of G-protein alpha subunits involved in
      cyclic AMP synthesis. A pilot study examining the ventrolateral subnucleus of the
      DR (DRvl) reveals that serotonin-1A receptors are increased in suicide victims
      with major depression as compared to normal control subjects. Altered signal
      transduction in cerebral cortex and altered regulation of serotonin neurons in
      the DR may be important in the pathophysiology of major depression and suicide.

PMID- 9616802
TI  - Pathophysiology of the locus coeruleus in suicide.
AB  - Clinical and basic research findings implicate a role for brain norepinephrine in
      the pathophysiology of psychiatric disorders that can lead to suicide. However,
      the precise biological abnormality of neurons that produce norepinephrine in the
      brain in these disorders has not been elucidated. We have studied the
      biochemistry of the locus coeruleus (LC), the principal source of brain
      norepinephrine, from suicide victims and from age-matched, natural or accidental
      death control subjects. Levels of tyrosine hydroxylase (rate-limiting enzyme in
      norepinephrine biosynthesis) and amounts of binding to a2 adrenoceptors
      (norepinephrine receptors) are elevated in the LC of suicide victims as compared
      to control subjects. These biological abnormalities in the LC from suicide
      victims are very similar to biochemical changes observed in the rat LC following
      repeated exposure to environmental stimuli that activate the LC or to treatment
      with pharmacological agents that deplete brain norepinephrine. It is hypothesized
      that persons who commit suicide have experienced chronic activation of the LC,
      resulting in depletion of synaptic norepinephrine and compensatory changes in
      concentrations of noradrenergic proteins.

PMID- 9616803
TI  - Morphometric methods for studying the prefrontal cortex in suicide victims and
      psychiatric patients.
AB  - Neurochemical studies demonstrate altered numbers of monoaminergic receptors in
      the prefrontal cortex in suicide and depression victims, implicating dysfunction
      of the prefrontal cortex in the neuropathology of suicide and psychiatric
      disorders. Neuroimaging studies in vivo have revealed an altered pattern of
      cortical metabolism and reductions in frontal lobe volume in patients with
      schizophrenia (SCZ) or depression. However, the precise morphopathology
      underlying these abnormalities and their relevance to suicide are unknown. Our
      recent three-dimensional cell counting of dorsolateral prefrontal cortex from 16
      postmortem SCZ brains (10 suicide completers) revealed cellular changes
      (increased neuronal density, and reduced laminar width and neuronal size) that
      may be associated with neuroimaging observations. Evaluation of the same
      morphometric parameters in the prefrontal cortex in seven bipolar brains (three
      committed suicide) revealed similarities (decreased cortical and laminar
      thickness) and differences (unchanged overall neuronal density and laminar
      densities) between morphopathology of SCZ and bipolar disorder. In another
      population of suicide victims with major depression (nonpsychotic), further
      morphopathological differences from SCZ and similarities to bipolar disorder were
      observed in the prefrontal cortex. From these data we can conclude that the
      morphopathology observed in brain tissue from suicide victims appears to vary
      based on psychiatric symptomatology. In order to confirm this hypothesis and to
      establish the specificity of morphometric findings in relation to psychiatric
      disorders and suicide, additional studies are warranted in nonsuicide subjects
      with SCZ, major depression, or bipolar disorder.

PMID- 9616804
TI  - Postmortem findings in suicide victims. Implications for in vivo imaging studies.
AB  - Alterations in serotonergic and noradrenergic receptor binding in membrane
      homogenates from the brain of suicide victims suggest a biological substrate for
      the vulnerability to commit suicide. We and others have employed high-resolution
      quantitative autoradiography of full coronal sections of the prefrontal cortex to
      map the locus of maximal change in receptor binding. We found alterations in
      binding to the serotonin transporter, the 5-HT1A, and the 5-HT2A receptors
      primarily in the ventral and ventrolateral prefrontal cortex of suicide victims.
      Importantly, these changes are often modest in magnitude and anatomically
      restricted to one or two Brodmann areas. Furthermore, we have found that care in
      case selection is essential, because sex, age, drugs, and comorbid diagnoses
      contribute to receptor binding. The implications for in vivo imaging are
      considerable, directing the focus of such studies toward the ventrolateral
      prefrontal cortex. However, because ligands are limited, as is the resolution of
      current methods, including PET, automated analyses that produce statistical
      images, rather than manual selection of individual slices, will likely lack the
      ability to detect the discrete receptor changes found postmortem. Alternatively,
      the advantages of examining large numbers of subjects, imaging the entire brain,
      obtaining detailed clinical information in the living patient, and magnifying the
      changes with neuropharmacological challenges present a promising outlook for
      making major advances into the identification of brain abnormalities associated
      with suicide risk.

PMID- 9616805
TI  - Suicide: a four-pathway clinical-biochemical model.
AB  - This chapter, based on a review of recent research as well as data presented in
      this report, proposes four hypothetical pathways leading to suicide in clinical
      depression: (1) an acute pathway involving severe anxiety/agitation associated
      with high brain corticotrophin-releasing factor (CRF or CRH) levels, (2) trait
      baseline and reactivity hopelessness, (3) severe anhedonia, and (4) trait
      impulsiveness associated with low brain serotonin turnover and low total
      cholesterol as a possible peripheral correlate. Clinical research showing
      evidence for acute versus chronic high-risk suicide factors and other studies
      linking severe anxiety/agitation to high CRF levels will be presented as
      associated with acute suicidal risk, which is potentially reversible with
      recognition and treatment. Evidence for anhedonia severity as a risk factor and
      trait, as well as evidence that baseline hopelessness and sensitivity are traits
      related to chronic suicide risk, will be presented. Finally, evidence relating
      low serum cholesterol to suicide in depressed inpatients will be presented in the
      context of literature suggesting a relationship between low serum cholesterol and
      violent death and suicide in population studies. Data suggesting a relationship
      between low serum cholesterol and decreased CSF 5-HIAA, suggesting reduced
      serotonin turnover, will be presented, in light of prior studies relating low CSF
      5-HIAA and violent suicide. These data taken together suggest four pathways to
      suicide that are worth investigating in order to better understand the mechanisms
      leading to this behavior. Future possibilities and applications of these findings
      are discussed.

PMID- 9616806
TI  - Behavioral treatments of suicidal behaviors. Definitional obfuscation and
      treatment outcomes.
AB  - This chapter focuses on a review of randomized clinical trials of both
      psychosocial and behavioral interventions designed to directly reduce rates of
      suicide and parasuicidal behavior, including suicide attempts. It begins with an
      overview of the definitional difficulties in this field and then proceeds to an
      overview of treatment issues and a comprehensive review of treatment studies
      aiming to reduce suicidal behavior among suicidal individuals. Twenty studies are
      discussed. Eighteen studies randomly assigned subjects to the experimental and
      control condition; the other two studies assigned subjects in an alternating
      sequential fashion. Analyses showed that four psychosocial intervention studies
      and one pharmacotherapy study have reported efficacious results when compared to
      treatments-as-usual or placebo controls. From another perspective, when
      outpatient psychosocial interventions were examined, the strongest predictor of
      whether the experimental treatment would be more effective than the control was
      whether high-risk suicidal individuals were included. Psychosocial interventions
      appear to be most effective with the more high-risk individuals.

PMID- 9616807
TI  - Suicide and antidepressants.
AB  - Suicidal thoughts and suicide attempts are an integral part of various
      depressions. Suicide attempts are common in major depression but even more common
      in recurrent brief depression, and the rate is further increased when these
      depressions occur comorbidly. Combined depression, where recurrent brief
      depression and major depression coexist, is the strongest clinical predictor of
      suicide attempts in the literature. There have been very few controlled studies
      of treatments for depression in high-risk groups of suicide attempters.
      Psychotherapy has been found to significantly raise the suicide attempt rate
      compared with conventional treatment, whereas fluoxetine and mianserin were not
      different from placebo. The only treatment that has been found to lower the
      suicide attempt rate in those with a history of previous suicide attempts is low
      doses of flupenthixol, a neuroleptic licensed for depression in Europe. This drug
      had a significant advantage compared with placebo in a six-month study. There are
      indications from large studies that maprotiline and amitriptyline might raise the
      suicide attempt rate, compared with placebo or other antidepressants, independent
      of their inherent toxicity in overdose. Several analyses of coroners' data show
      that tricyclic antidepressants are associated with high and unacceptable death
      rates in overdose compared with SSRIs and other safer antidepressants. Toxic
      antidepressants should be avoided in those thought to be at particular risk.

PMID- 9616808
TI  - Effect of lithium maintenance on suicidal behavior in major mood disorders.
AB  - We reviewed evidence of a possible antisuicide action of lithium maintenance
      treatment in mood disorders. Of 28 published studies involving over 17,000
      patients with major affective illnesses, most yielded supportive evidence: risk
      of suicides and attempts averaged 3.2 versus 0.37 per 100 patient-years without
      versus with lithium (8.6-fold difference). In a new study of 284 bipolar I- and
      II-disordered patients, corresponding rates (2.2 vs. 0.39/100 patient-years)
      differed by 5.6-fold (p < 0.001); moreover, after discontinuing lithium, rates of
      suicidal acts rose by 7-fold (16-fold within the first year), and fatalities
      increased by nearly 9-fold. Lithium maintenance treatment in recurring major mood
      disorders has strong evidence of antisuicide effects not demonstrated with any
      other mood stabilizer. Close association of suicide and depression in bipolar
      disorder emphasizes the need for improved identification and treatment of bipolar
      depression.

PMID- 9616809
TI  - A synthesis of current findings regarding neurobiological correlates and
      treatment of suicidal behavior.
AB  - Considerable progress has been made in the study of neurobiological correlates of
      suicidal behavior. These studies have confirmed the link between reduced
      serotonergic function and serious suicidal acts. They have localized the changes
      to the ventral prefrontal cortex and suggested how genetics, childhood rearing,
      alcoholism, substance abuse, gender, age, and cholesterol intake can modulate
      suicide rates through effects on the serotonergic system. Future studies need to
      apply this knowledge in the development of in vivo brain imaging and molecular
      genetic probes for study of high-risk patients. Identification of high-risk
      groups is essential for the conduct of controlled treatment trials, which are
      presently almost entirely lacking in suicidal populations. Previous clinical
      trials of medications and psychotherapies have targeted axis I or axis II
      disorders but not the predisposition to suicidal acts. Controlled treatment in
      high-risk patients must be undertaken to identify interventions that can reduce
      the propensity for suicidal acts. Such interventions will supplement current
      treatment strategies that target the associated psychiatric illness and reduce
      the opportunities to attempt suicide in high-risk patients by hospitalization.

PMID- 9616810
TI  - [Means of diagnosis of Chlamydia pneumoniae infection].

PMID- 9616811
TI  - [Chlamydia pneumoniae and respiratory pathology. Epidemiological data].

PMID- 9616812
TI  - [Chlamydia pneumoniae and asthmatic disease in adults: relations to be
      clarified].

PMID- 9616813
TI  - [Role of Chlamydia pneumoniae in asthmatic disease in children].

PMID- 9616814
TI  - [Does infectious asthma exist?].

PMID- 9616815
TI  - [For a new diagnostic approach of obstructive sleep apnea syndrome in adults].

PMID- 9616816
TI  - [Use of helium-oxygen gas mixtures in acute obstructive respiratory
      insufficiencies].
AB  - Therapeutic use of helium has been described since 1930. Its main action is to
      reduce bronchial resistances and consequently overall respiratory work. Helium is
      substituted for nitrogen. The effects of inhaling a helium-oxygen mixture result
      exclusively from the physicochemical properties of helium: very low density, high
      kinetic viscosity. With the advent of selective bronchodilators, use of helium
      was rapidly abandoned until recently with new interest for the treatment of
      severe acute asthma. We review the literature on the physical properties of
      helium-oxygen mixtures and propose an analysis of their therapeutic use in severe
      acute asthma as well as other indications such as acute episodes of obstructive
      bronchopneumonia and obstruction of the upper airways. Due to the non-invasive
      nature of this technique, its easy use with spontaneous ventilation and the large
      body of theoretical data emphasizing its adaptation for therapeutic use, helium
      oxygen gas mixtures offer an important therapeutic option for treating severe
      diseases with poor prognosis. A multicentric national study is under way to
      validate its use early by emergency ambulatory units for the treatment of severe
      acute asthma.

PMID- 9616817
TI  - [Dose-effect of adrenaline nebulization in asthma: comparative study with
      salbutamol].
AB  - The aim of this randomized cross-over trial was to evaluate the dose effect and
      systemic absorption of epinephrine nebulized at 2 and 5 mg in comparison with
      salbutamol (5 mg). Thirteen asthmatic patients (29 +/- 15 years, 4 men and 9
      women) were randomly assigned to receive one nebulization of each of the three
      treatment regimens at 24 h interval. The evaluation concerned forced expiratory
      volume in 1 second (FEV1), heart rate, respiratory rate and arterial pressure.
      All measurements were done at baseline, every 15 minutes during the first hour,
      and hourly thereafter until return to baseline FEV1. Serum potassium was measured
      at baseline (T0) and sixty minutes after (T60). Plasma levels of epinephrine were
      measured at T0, T20, T60. Fifteen minutes after the beginning of nebulization
      FEV1 improved significantly over baseline in the three groups. These changes were
      similar in the three groups until T45, while FEV1 improvement was significantly
      greater in A5 and S groups than A2 group (+640 +/- 470 ml, +721 +/- 349 ml, +406
      +/- 306 ml in A5, S and A2 groups respectively, p < 0.01). Bronchodilation lasted
      significantly longer with salbutamol than with epinephrine (p < 0.05). No side
      effects were recorded in spite of substantial and dose-dependent systemic
      absorption of epinephrine. CONCLUSION: Increasing epinephrine doses produces
      greater bronchodilation without additional side effects. However this
      bronchodilation lasts shorter than with salbutamol.

PMID- 9616818
TI  - [Etiologies of pleurisies in African milieu. Experience of the Cocody Pneumology
      department (Abidjan-Cote d'Ivoire)].
AB  - We analyzed hospital files of 614 pleurisy patients at the Cocody University
      Hospital over a 5 year period (1990-1994). We searched for the main etiologies of
      pleural effusion in these patients in order to propose an empirical treatment.
      Pleurisy is involved in 23% of all respiratory patients seen each year. Pleural
      effusions are observed in 91% of the cases. Clear fluid was observed most
      frequently (65%), followed by purulent (31%) and hemorrhagic effusion (4%). The
      dominant etiology was tuberculosis (66%). Non-tuberculosis infections were found
      in 5% of the cases. Tumoral diseases were involved in 3% and ambiasis in 1%. The
      cause of the pleural effusion remained unidentified in 24%. In 59% of the cases
      treatment was initiated without a definitive diagnosis. The incidence of HIV
      infection was high: 167 seropositive patients (72%) among the 231 patients
      tested. In conclusion, infections are the predominant etiologies of pleurisy at
      the Cocody University Hospital (72%) and the high frequency of tuberculosis
      argues for empirical antituberculosis therapy if no cause is identified.

PMID- 9616819
TI  - [A tropical pulmonary nodule].
AB  - The authors report a case of american pulmonary histoplasmosis discovered by
      chance on a chest radiograph in a non immunocompromised patient, back from a stay
      in French Guyana. Confronted with the negativity of usual mycotic research,
      diagnosis has been made thanks to wedge excision by video-assisted thoracic
      surgery. The authors briefly sum up the recent facts regarding this imported
      infection, stressing the interest of a direct approach by surgical practices not
      very invasive that allow to eliminate with certainty neoplasm or tuberculosis.

PMID- 9616820
TI  - [Primary malignant mediastinal melanoma. Apropos of a case].
AB  - We report the case of a 57-year-old patient with primary malignant melanoma of
      the mediastinum who survived nine months despite immunotherapy, radiotherapy and
      chemotherapy. The primary nature of the intrathoracic melanoma was difficult to
      prove. Definitive diagnosis was based on the uniform morphology of the melanoma
      which showed junctional anomalies at the histology examination with tracheo
      bronchial and esophageal localizations as well as on the absence of other patent
      or formerly resected melanocyte-rich localizations (skin, mucosa, ocular) at
      clinical examination and autopsy.

PMID- 9616821
TI  - [Bronchiolitis obliterans organizing pneumonia: a complication of radiotherapy].

PMID- 9616822
TI  - [Management of severe amiodarone-induced pneumopathy using inhaled nitric oxide].
AB  - Treatment of amiodarone-induced pulmonary toxicity generally consists in simply
      discontinuing the drug with subsequent improvement in clinical condition and
      radiologic abnormalities. Corticosteroid therapy, when used, may accelerate
      recovery. Early diagnosis is however necessary and mandates the immediate
      cessation of the drug otherwise diffuse interstitial and alveolar damage can
      develop and lead to acute respiratory distress syndrome with a high rate
      mortality. To our knowledge, the use of inhaled nitric oxide to improve arterial
      oxygenation in amiodarone-induced ARDS has not yet been described. Here we report
      the case of a patient in whom 2 ppm inhaled nitric oxide in association with
      mechanical ventilation dramatically improved a life-threatening hypoxemia. We
      therefore submit that inhaled nitric oxide could be of benefit in patients with
      amiodarone-induced ARDS.

PMID- 9616823
TI  - [Use of serum tumor markers in managing primary bronchial cancers:
      recommendations].

PMID- 9616824
TI  - [Transbronchial biopsy and bronchiolitis obliterans organizing pneumonia].

PMID- 9616825
TI  - [Pollen environment and its evaluation].
AB  - We review the methods available for determining airborne pollen. In addition to
      the classical gravimetric and volumetric methods, new immunochemical techniques
      are also used for detecting allergenic pollen and measuring of the size of
      allergen-carrying particles. Pollen counts are available in France for 39 urban
      sites. In the last decade changes in the pollen environment have basically
      concerned higher counts from resinous trees in southern France and birch tree
      counts in northern France as well as a lesser role for ash trees. Among the
      recent acquisitions, it has been demonstrated that allergens are present in twigs
      and leaves, or even the bark of certain trees. Interactions with atmospheric
      pollution is better understood and could be a contributing factor to the
      increasing number of people allergic to pollen. Pollen allergens can be carried
      on particles of various sizes and immunochemical studies have demonstrated that
      gramineous pollen allergens can be carried on starch particles less than 3 mu in
      diameter. These recent studies would explain the apparent disagreement between
      pollen counts and the number of clinical manifestations.

PMID- 9616827
TI  - [Middle lobe syndrome: apropos of 5 cases].
AB  - We present 5 cases of middle lobe syndrome. We discuss the etiologic aspects.
      Fibroptic bronchoscopy must be systematic. Treatment is conservative or surgical.

PMID- 9616826
TI  - [Efficacy and tolerability of pristinamycin vs amoxicillin-clavulanic acid
      combination in the treatment of acute community-acquired pneumonia in
      hospitalized adults].
AB  - The aim of this double-blind, 2 parallel group, randomized, multicenter study was
      to compare the efficacy and the safety of pristinamycin (P), 1 g bid, versus
      amoxicillin-clavulanic acid (AAC), 500 mg q.i.d., for 10-14 days in the treatment
      of non severe community-acquired pneumonia in hospitalized adults. From December
      1992 to July 1994, 180 patients were included: 92 in the group P and 88 in the
      group AAC. The both groups were similar on demographic, clinical and
      bacteriological criteria. 96 pathogens of which more than half were pneumococci,
      were isolated in 79/180 (44%) patients. The primary assessment was the global
      success rate defined as long-term (D40 +/- 7), clinical, radiological and
      bacteriological efficacy in the "per protocol" population (75 patients in the
      group P and 83 in the group AAC). The global success was obtained in 63/75 (84%)
      patients in the group P and 70/83 (84.3%) patients in the group AAC. At the end
      of treatment (D14 +/- 3), theses rates were respectively 85.4% and 84.3%. The
      both treatments were equivalents. Adverse events (mainly gastro-intestinal
      disorders) were reported by 55/92 (59.8%) patients in the group P and 49/87
      (56.2%) patients in the group AAC.

PMID- 9616828
TI  - [Lymphocytic alveolitis, chronic viral hepatitis C, lipoproteinosis and
      cryoglobulinemia in a patient].
AB  - Chronic hepatitis C virus (HCV) infection, lipoproteinosis and cryoglobulinemia
      may all be associated with lymphocyte alveolitis. The pathogenic mechanisms
      involved would suggest a compromised immune system. We report the first
      observation of a patient with lipoproteinosis, cryoglobulinemia and hepatitis C
      virus infection who developed lymphocyte alveolitis. Taken individually, each of
      these three disease states could explain cellular modifications observed in the
      lung, but their association aggravated the clinical course.

PMID- 9616829
TI  - [Reactive airway dysfunction syndrome and bronchiolitis obliterans after exposure
      to acid vapors].
AB  - A 37-year-old male non-smoker developed rapidly severe respiratory disease after
      a 3-hour exposure to hydrobromic acid fumes. An upper airway syndrome ensued with
      anosmia and aphonia as well as non-specific bronchial hyperreactivity,
      obstructive bronchiolitis (which led to a persistent respiratory volume of about
      20% of the normal level with exercise-induced dyspnea) and obstructive
      bronchiolitis. Lung transplantation is currently being considered. When inhaled
      at irritant concentrations, certain toxic gases, such as chlorine, can lead to
      reflex apnea via laryngeal nerve reaction, limiting gas penetration into the
      bronchial tree. Other gases are cell toxins and can enter the deeper part of the
      lung before provoking irritating cough. This is what occurred for our patient who
      continued work in the polluted atmosphere until his severe cough obliged him to
      leave his job. This case is an example of cellular toxicity resulting from
      atmospheric gas fumes at low weakly-irritative concentrations, explaining the
      insidious nature of disease onset.

PMID- 9616830
TI  - [A rare biphasic pulmonary tumor, carcinosarcoma. A separate entity or
      differentiation variant of spindle-cell carcinoma?].
AB  - We report a case of pulmonary carcinosarcoma. Surgery is required for this rare
      mixed type, biphasic tumor. It is generally considered to be a malignant
      formation issuing from a single cell line but with a two-way differentiation into
      epithelial and conjunctive components. There is a differentiation continuum
      between spindle-cell carcinomas (also called monophasic sarcomatoid carcinoma)
      and carcinosarcoma (or biphasic sarcomatoid carcinoma) leading to debate
      concerning the immunohistochemical and ultrastructural features.

PMID- 9616831
TI  - [Sarcoidosis in a patient with Crohn disease].
AB  - Extra-intestinal manifestations of inflammatory bowel disease (Crohn's disease)
      are frequent although pulmonary signs are uncommon. We report the case of a
      patient with sarcoidosis and inflammatory bowel disease and discuss the common
      features of these two diseases.

PMID- 9616832
TI  - [Respiratory manifestations of carbamazepine. Apropos of a case].
AB  - A 14-year-old girl developed skin rash, fever and dyspnea. The chest
      roentgenogram showed diffuse reticulonodular infiltration. Pulmonary function
      tests revealed mild restrictive defect and blood oxygen pressure at 71 mm Hg. BAL
      showed increased cell counts with lymphocytosis at 15% and neutrophilia at 3%.
      Outcome was good after carbamazepine withdrawal and without corticosteroid
      therapy. Relapse was observed after patient-induced rechallenge.

PMID- 9616833
TI  - [Neoplastic pulmonary embolism. An uncommon cause of acute respiratory distress
      with normal pulmonary radiography].
AB  - The incidence of neoplastic pulmonary embolism is certainly underestimated
      Necroscopy series report figures varying from 2.9 to 26. The clinical
      manifestations are similar to those observed in cruoric pulmonary embolism. We
      report two cases of acute respiratory failure with normal chest X-ray in which
      the diagnosis was neoplastic pulmonary embolism. The difficulties encountered for
      diagnosis resulted from the diffuse microvascular nature of the lesions.
      Perfusion scintigraphy and Swan-Ganz catheterism can be contributive, but certain
      diagnosis requires pathology examination. Prognosis is very poor. Clinicians
      should be aware of this pathology and entertain the diagnosis in all cor
      pulmonale patients with acute respiratory failure and a normal chest X-ray.

PMID- 9616834
TI  - [Cardiac arrest and vinorelbine? Apropos of a case and review of the literature].
AB  - Cardiotoxicity is not a well-known complication of the administration of
      vinorelbine (Navelbine). We report a case of cardiogenic shock with pulmonary
      edema after administration of vinorelbine within an association of radiotherapy
      and chemotherapy.

PMID- 9616835
TI  - [Lymphoma on a collapse therapy pouch. A new case].

PMID- 9616836
TI  - [Notion of metabolic adaptation to exercise].
AB  - During muscular exercise, adenosine triphosphate (ATP) must be resynthesized in
      order to allow subsequent muscle contraction. ATP can be immediately
      resynthesized from adenosine diphosphate (ADP) and from creatine phosphate (CP).
      However, such resynthesis from phosphorylated compounds is not possible in very
      short-duration exercise. For further exercise an energy source, mainly
      carbohydrates and lipids, is needed. While anaerobic (glycolysis and
      glycogenolysis) and aerobic (mitochondrial oxidation) pathways are used for
      carbohydrates, lipids can only undergo oxidation. Carbohydrates are used
      preferentially with rising exercise intensity because of increased muscle uptake,
      progressive recruitment of type II fibers and catecholamine release. Lipid
      oxidation rises with the duration of exercise and falls with increasing
      intensity. The observation that training plays an important role in the use of
      these energy substrates has led to the development of the crossover theory by
      which the use of carbohydrates and lipids in all individuals depends at all times
      on the combined effect of training and exercise intensity. Training facilitates
      lipid oxidation but, by allowing higher intensity, also implies inevitable use of
      carbohydrates. Thus there is an exercise level, or a crossover point, at which
      carbohydrate energy predominates over lipid energy. Beyond this point, increasing
      energy requirements are satisfied by preferential use of carbohydrates. Finally,
      although it was incorrectly thought that proteins play a very minor role,
      actually amino acids coming from the voluminous tissue mass provide an important
      source of energy during prolonged exercise.

PMID- 9616837
TI  - [Cardiorespiratory adaptations to exercise].
AB  - For the organism, adaptation corresponds to a physiological response to a problem
      raised by a modification in the internal medium and/or the environment while
      preserving homeostasis. Adaptations to muscle exercise can involve changes in
      metabolic, respiratory, or nutritional, or nutritional functions or any other
      modifications whose endpoint is the production more ATP for further muscle
      exercise. Adaptations occur at all the levels of the oxygen transport chain. We
      will thus focus successively on the notions of VO2max, ventilatory adaptations,
      thresholds, respiratory exchange, cardiac and vascular adaptations and peripheral
      adaptations.

PMID- 9616838
TI  - [Value and indications of exercise test in pneumology].
AB  - Exercise testing is the only integrate exploration technique, i.e., a technique
      which tests pulmonary, cardiac and muscular function, currently available in
      pneumology. The first indication for exercise testing in pneumology is to
      evaluate the exercise capacity of dyspnea patients. This can be done by measuring
      exercise tolerance and by differentiating each of the elements in the oxygen
      transport chain which can contribute to the dyspea, from a classical diagnostic
      standpoint, the exercise test can be used to screen for post-exercise asthma or a
      right-left shunt, estimate the severity of respiratory disease by demonstrating,
      for example, exercise-induced hypoxia. The exercise test also plays a fundamental
      role in preoperative evaluation prior to surgical resection of lung
      transplantation. It can also serve as a natural follow-up for treatment of
      respiratory diseases. One final and fundamental indication for exercise.

PMID- 9616839
TI  - [Factors limiting exertion in respiratory diseases].
AB  - Factors limiting exercise capacity in patients with respiratory disease are
      determined in part by their response to an exercise test. Exercise tests evaluate
      the overall oxygen transport chain, i.e. exercise tolerance. The basic parameter
      is maximal oxygen consumption, VO2max which is very low in respiratory diseases.
      Decreased exercise tolerance results first from limited ventilatory capacity at
      maximal exercise: ventilatory reserve in these patients is low. At submaximal
      exercise, ventilation is on the contrary increased for a given exercise load.
      This relative hyperventilation is the consequence of the patient's general poor
      physical condition. In these patients the cardiovascular response to exercise is
      impaired because of decreased systolic ejection fraction related to bronchial
      obstruction. Finally, whatever investigation method is used, the metabolic
      response in patients with respiratory disease, i.e. peripheral muscle response,
      is greatly impaired. The aerobic is deficient and the anaerobic pathway
      predominates, sign that the sedentary status of these patients has altered their
      metabolic response.

PMID- 9616840
TI  - [What equipment to be chosen, with what criteria, and what requirements?].
AB  - The increasing precision of exercise testing modalities has contributing to
      making it an excellent means of evaluating functional impairment in dyspnea
      patients. It has become an indispensable diagnostic tool. Interpretation of data
      acquired during an exercise test depends on the reliability of data collection
      and the accuracy of the different calculations. The wide variety of available
      measurement systems (different principles, different methods for measuring lung
      volumes and ventilatory flow, canalization systems and valves, analyzers) and
      data processing systems, and the presence of very simple or on the contrary very
      complicated systems emphasizes the importance of determining quality requirements
      used for selecting equipment.

PMID- 9616841
TI  - [Common and current measurement parameters].
AB  - The different parameters used in cardiopneumologic exercise tests allow an
      assessment of exercise tolerance on the basis of the subject's ventilatory
      response, cardiac and metabolic adaptation and gas exchanges during exercise.
      VO2max and dyspnea are indicators of good or poor exercise tolerance. Normal
      values established for adults in three reference articles depend on age, body
      weight and height. In a 20-year-old non sedentary subject, VO2max is
      approximately 45 ml/mn/kg and decreases to 25 ml/mn/kg at 65 years of age.
      Dyspnea is measured on two types of scales, categorical and visual analogue
      scales. "Minimal dyspnea" at maximal effort is normal in a healthy subject but
      becomes "very severe" in diseased subjects. A dyspnea threshold can be determined
      from the evolution of dyspnea during the test and is useful for retraining in
      patients with chronic obstructive lung disease. The normal ventilatory response
      always leaves a ventilatory reserve equal to 30% of the theoretical maximal
      ventilatory output. If the reserve is diminished, exercise is limited by
      ventilatory capacity. Gas exchanges reflect muscle adaptation to exercise and the
      homogeneous nature of alveolar ventilation compared with pulmonary perfusion
      (VA/Q). This depends on the physiological dead space (VD/VT) which is
      approximately 1/3 at rest decreasing to 1/4 or 1/5 at maximal exercise. VD/VT is
      high at rest and stays high during exercise in interstitial lung disease and
      vascular lung disease. VA/Q also depends on the alveo-arterial oxygen
      differential (P(A-a)O2) which increases two-fold during exercise. Expired gas and
      arterial gas must be measured simultaneously for the calculation. To measure
      cardiac adaptation, the ECG, heart rate and oxygen pulse (VO2/HR) must be
      recorded. The kinetics of oxygen pulse is more important than its maximal value,
      a decrease with unchanged heart rate suggests early-stage cardiomyopathy.
      Finally, blood lactate, the metabolic response to exercise, is used to determine
      the lactate threshold or the anaerobic threshold. Measurement of the ventilatory
      threshold is less invasive, ventilatory outflow increasing with increasing
      lactate level as described by the Beaver or Wassermann model. These thresholds
      indicate the subject's aerobic capacity. The exercise test has diagnostic value
      but can also be useful for individual patient management, particularly
      cardiorespiratory rehabilitation.

PMID- 9616842
TI  - [Evaluation of exercise-induced dyspnea].
AB  - Analogue scales are relatively easy to interpret for the assessment of exercise
      induced dyspnea although certain standardization points remain to be established.
      We discuss the pathophysiological basis correlating dyspnea with exercise
      parameters. In clinical practice, the curve of the dyspnea/ventilation ratio
      plotted during exercise is a useful parameter, focusing attention on the notion
      of a dyspnea threshold (near the ventilatory threshold) and slope (which could be
      modified, for example, by treatment or a rehabilitation program). Evaluation of
      exercise-induced dyspnea must of course be an integral part or the overall
      analysis of all other parameters studied during exercise.

PMID- 9616843
TI  - [Preparing patients to protocols of exercise test: necessity of
      individualization].
AB  - Dyspnea may be easily appreciated during exercise with dyspneic scales, but
      methodological standardisation still needs to be specified. Authors review the
      basic physiological mechanism relating dyspnea to indices obtained during a
      stress test. They propose to use the dyspnea/VE relationship. With the concept of
      dyspneic threshold (close to the ventilatory threshold) and the ramp that both
      could be modified (for instance by rehabilitation programmes including exercise
      training). Interpretation of dyspnea during an exercise test obviously needs to
      be integrated with other parameters studied during exercise.

PMID- 9616844
TI  - [Interpreting exercise tests].
AB  - The main objective of the maximal exercise test is to measure a patient's
      exercise limit and to identify the cause. The test to be interpreted is evaluated
      first by judging exercise tolerance on the basis of maximal oxygen consumption
      (VO2max or symptom-limited VO2(VO2 SL). Intolerance is moderate if VO2 is under
      85% of the theoretical level and severe when it is under 60%. Interpretation then
      consists in identifying the cause of the limitation. Ventilatory reserve is the
      main element for determining whether the limitation is due to ventilatory or
      cardiac impairment. In case of a ventilatory limitation, ventilatory reserve
      falls and the ventilatory pattern and gasometric values orient the diagnosis to
      emphysema, diffuse interstitial lung disease or bronchopneumopathy. If the
      ventilatory reserve rises, the limitation has cardiac as origin and in this case
      the oxygen pool is decreased. Persistence of chronotrope reserve can indicate
      coronary artery disease while the VD/VT ratio is useful for differentiating
      cardiac and vascular limitations. Peripheral limitations usually produce an early
      major increase in blood lactate, a high lactate/pyruvate ratio, with lactate or
      ventilatory thresholds under 40% of theoretical VO2max, especially in case of
      muscle pain and low watt equivalent. Nevertheless, these parameters cannot be
      used to confirm a precise diagnosis. The only positive diagnosis given by the
      exercise test concerns glycogenolysis disorders (por example McArdle's disease)
      seen as a total absence of increased lactate level. In conclusion, the exercise
      test is a means of assessing a patient's exercise tolerance and provides
      arguments for determining the origin of the limitation. However, as no one
      argument is truly pathognomonic, the diagnosis hypothesis must be based on all
      the elements available from clinical examination and complementary explorations.

PMID- 9616845
TI  - [Cardiopulmonary exercise test in cardiology].
AB  - In the cardiopneumologic exercise test, a concomitant analysis of respiratory gas
      exchange is conducted in addition to the usual cardiologic exercise test: After
      excluding patients with the habitual contraindications, the test must be
      conducted with a rigorous methodology, with particular care being given to
      standardizing the equipment settings before each test and in choosing an
      individualized protocol allowing a maximal test for a duration of no longer than
      10 to 12 minutes. This cardiopneumologic exercise test allows a good assessment
      of the pneumological pathophysiological factors participating in limited exercise
      capacity of cardiac origin. It can also help the clinician distinguish cardiac
      from pulmonary dyspnea, particularly by measuring ventilatory reserves at maximum
      effort. Most importantly, in clinical practice the test provides an objective and
      reproducible assessment of the patient's exercise capacity. This allows a
      functional classification useful for therapeutic decision making, as for example
      when determining the best moment to propose heart transplantation or when
      prescribing adapted exercise retraining for a heart failure patient. Finally, the
      exercise test provides objective evidence of symptom improvement, for example
      after rehabilitation, an improvement which is one of the mainstay objectives of
      treatment in patients with cardiac-related exercise intolerance.

PMID- 9616847
TI  - [Exercise test in pneumology. Synthesis. Prospects].

PMID- 9616846
TI  - [Exercise test in prescribing respiratory rehabilitation].
AB  - Pulmonary rehabilitation is indicated to a wide population of patients suffering
      of pulmonary diseases often associated to a cardiovascular disorder. Best
      evaluation of the results of an exercise program, must consider the alterations
      of pulmonary function tests, the cardiac dysfunction, the non specific bronchial
      hyperresponsivness and the lung inflation. Exercise test is often performed on a
      cycle ergometer with an incremental or a constant load. The indications of the
      exercise test are: diagnostic (evaluation of effort performance, ventilatory
      drive and looking for an associated disorder as cardiovascular, muscles or
      metabolic), therapeutic (individualization of exercise program) and scientific
      (objective evaluation of immediate and long term results).

PMID- 9616848
TI  - ECG changes during dobutamine stress test and spontaneous recovery of
      contractility in patients with myocardial infarction.
AB  - Recent reports suggest a relationship between ECG changes and myocardial
      viability during dobutamine stress echocardiography in patients with myocardial
      infarction. The aim of the study was to analyze the predictive value of T-wave
      normalization and ST segment elevation during low- (10 mucg/Kg/m') and high-dose
      (40 mucg/Kg/m') dobutamine stress test for late spontaneous recovery of function
      in patients with a first uncomplicated Q-wave myocardial infarction. METHODS:
      Seventy eight consecutive patients (59 +/- 9 yrs; males = 67; anterior MI = 41,
      inferoposterior MI = 37 pts) underwent baseline 2D echo and dobutamine stress
      test at 9 +/- 2 days from onset of symptoms and they were free of cardiac events
      during the first three months after myocardial infarction. T-wave normalization
      (negative T-wave becoming > or = 1 mm upright in > or = 2 leads) and ST segment
      elevation (> or = 0.1 mm in > or = 2 leads) at low- and high-dose dobutamine
      infusion were compared with an improvement of contractility in the infarct area
      detected echocardiographically at three months. A wall motion score decrease in
      infarct area > or = 2 was the criterion for recovery of contractility. RESULTS:
      ST segment elevation occurred in 19/78 patients at low dose (24%) and in 45/78
      patients at high dose (58%). Late recovery of contractility in the infarct area
      was observed in 38/78 patients (49%). The positive and negative predictive values
      of ST segment elevation for late recovery of contractility were, respectively, 63
      56% at low dose and 47-48% at high dose. A baseline negative T-wave in > or = 2
      leads was present in 56 patients, and 27 (48%) showed recovery of contractility
      at three months. T-wave normalization occurred in 14 patients at low-dose (25%)
      and in 29 patients at high-dose dobutamine infusion (52%). The positive and
      negative predictive values of T-wave normalization were, respectively, 71-59% at
      low dose and 62-67% at high dose. Both ECG markers were present in 10/56 patients
      at low dose and in 19 patients at high dose. The positive and negative predictive
      values, respectively, were 70-57% at low dose and 58-57% at high dose. At
      univariate analysis, neither the ECG changes alone nor their combination during
      dobutamine stress testing were shown to be significant predictors of recovery of
      function. CONCLUSIONS: Our study demonstrates that in patients with a first
      uncomplicated Q-wave myocardial infarction, the T-wave normalization and/or the
      ST segment elevation occurring during early dobutamine stress testing are not
      reliable predictors of late spontaneous recovery of contractility in the infarct
      area.

PMID- 9616849
TI  - Evaluation of mean right atrial pressure by two-dimensional and Doppler
      echocardiography in patients with cardiac disease.
AB  - BACKGROUND: Several approaches have been used for noninvasive estimation of right
      atrial pressure (RAP), but, no currently available method has gained any definite
      validation. The purpose of this study was to evaluate the accuracy of two
      dimensional and Doppler echocardiography in estimating mean RAP in patients with
      cardiac disease. METHODS: We examined the relation of mean RAP to right atrial
      size and function, size and respiratory changes of inferior vena cava and Doppler
      parameters of tricuspid and hepatic vein flow in 114 consecutive patients (77
      men, 37 women; mean age 57 +/- 12 years) with various cardiac diseases undergoing
      cardiac catheterization. Echocardiographic studies were performed within 24 hours
      before catheterization (mean interval 6 +/- 3 hours). Patients were assigned to 3
      groups according to the values of mean RAP (group 1, < or = 8 mmHg; group 2,
      between 9 and 12 mmHg; group 3, > 12 mmHg). RESULTS: Mean RAP ranged from 3 to 20
      mmHg (mean 9.1 +/- 4.3 mmHg). It correlated most strongly with the collapsibility
      index of inferior vena cava (IVCCI) (r = -0.76), minimal inspiratory diameter of
      inferior vena cava (r = 0.72) and deceleration time of early tricuspid flow (DT)
      (r = -0.61). Discriminant analysis demonstrated that IVCCI and DT were major
      determinants of mean RAP with 81.6% of cases correctly assigned to study groups:
      96% of patients of group 1 and 87% of patients of group 3 were identified,
      whereas the accuracy in identifying the patients of group 2 was lower (46%). An
      IVCCI > 45% was the best cutoff point in predicting a mean RAP < or = 8 mmHg; an
      IVCCI < 35% and a DT < 150 msec were the best cutoff points in predicting a mean
      RAP > or = 15 mmHg. The best multivariate equation predicting mean RAP was: mean
      RAP = 23.3 - 0.2 IVCCI -0.026 DT (r = 0.80, R2 = 0.64). This equation was 81%
      sensitive and 84% specific in detecting a mean RAP < or = 8 mmHg and 74%
      sensitive and 97% specific in detecting a mean RAP > 12 mmHg. CONCLUSIONS: Mean
      RAP can be estimated noninvasively by two-dimensional and Doppler
      echocardiography. The combined analysis of IVCCI and DT provides an accurate
      prediction on mean RAP < or = 8 mmHg and > 12 mmHg, whereas the prediction of
      intermediate values is less accurate.

PMID- 9616850
TI  - Isolated neonatal atrial flutter: clinical features, prognosis and therapy.
AB  - BACKGROUND: Concern exists in literature about the clinical course, the best
      acute and chronic treatment and the prognosis of idiopathic neonatal atrial
      flutter. The aim of our study was to evaluate this in a population of our
      patients with this type of arrhythmia. METHODS: Six infants (3 M, 3 F, mean age
      42 +/- 62 days, range 1-150) affected with atrial flutter without structural
      heart disease were studied and then acutely and chronically treated. The
      effectiveness of chronic antiarrhythmic treatment was evaluated with Holter
      monitoring every 3 months for the first year of life and with transesophageal
      atrial pacing. RESULTS: Mean arrhythmia cycle length was 180 +/- 34 ms with
      atrioventricular conduction ratio ranging between 1:1 and 3:1. Two patients with
      clinical signs of heart failure were successfully treated with DC shock.
      Transesophageal overdrive atrial pacing was successfully used in one patient
      treated with i.v. propafenone without benefit. In the remaining three patients,
      cardioversion was achieved with amiodarone after digoxin had failed in all three
      and propafenone had failed in two of them. To prevent recurrences, we treated
      four patients with amiodarone, one with amiodarone combined with propranolol and
      one with digoxin. During the follow-up (22 +/- 11 months), neither arrhythmia
      recurrences nor side-effects of the therapy occurred. CONCLUSIONS: Neonatal
      atrial flutter is an arrhythmia with significant acute morbidity but an excellent
      long-term prognosis. Electrical cardioversion is the first-choice treatment when
      the arrhythmia is not well-tolerated hemodynamically, while class III
      antiarrhythmic drugs such as amiodarone should be preferred in the other cases.

PMID- 9616851
TI  - [The utility of various Doppler parameters at rest and during exercise for the
      diagnosis of residual stenosis after operation for aortic coarctation. A doppler
      nuclear magnetic resonance comparison].
AB  - BACKGROUND: The postoperative follow-up of aortic coarctation (AoCo) is often
      characterized by persistent arterial hypertension, sometimes due to a residual
      narrowing at the site of surgical repair. A residual stenosis > or = 30% is
      considered to be significant. Anatomy of the aortic arch is best assessed by
      angiography, transesophageal echocardiography and magnetic resonance imaging
      (MRI). The use of these invasive and expensive procedures for routine examination
      in all patients who develop late systemic hypertension cannot be justified.
      Consequently, it would appear to be useful to find some noninvasive methods, such
      as Doppler gradients, that are capable of identifying any residual anatomic
      narrowing. OBJECTIVES: We compared different Doppler parameters obtained at rest
      and during exercise with the degree of narrowing at the site of surgical repair
      measured by MRI, in order to identify the indices predictive of residual
      stenosis. METHODS: Thirty-nine patients (26 M, 13 F) were studied after AoCo
      repair. Mean age was 21.7 +/- 9.7 years (9-49). Their age at the time of repair
      was 10 +/- 9.7 years (0.1-27) and the postoperative follow-up was 11.5 +/- 6
      years (2-25). Systolic blood pressure measurement and Doppler echo for
      calculation of the transisthmic gradient at rest and during exercise on a bicycle
      ergometer were performed in all patients. The peak systolic gradient (PGs) over
      the isthmus was calculated using the simplified Bernoulli equation: PGs = 4 x
      (V2(2)-V1(2)), where V1 and V2 are the peak velocities in the ascending and
      descending aorta. In addition, at the end of exercise the peak diastolic gradient
      (PGd) was measured at the end of the T wave on the ECG, and the systolic velocity
      half-time (SVHT), as the time interval from the peak to the half peak systolic
      velocity. MRI of the aorta was performed to measure the diameter of the isthmus
      (AI) and of the descending aorta at the diaphragm (DA). Residual narrowing at the
      isthmus was expressed as stenosis % = [(1-(AI/DA)]%. RESULTS: At rest: systolic
      blood pressure 128.3 +/- 22.5 mmHg, PGs 15.9 +/- 8.1 mmHg (1-32). None of the
      patients had PGd. At peak exercise: systolic blood pressure 207 +/- 37 (160-265)
      mmHg, PGs 32.3 +/- 14.7 mmHg (8-70), SVHT 96 +/- 23 msec (60-139) and PGd 7.2 +/-
      4.8 mmHg (1-17). Stenosis % measured by MRI was 23.1 +/- 14.5% (0-53) and in
      particular, it was < 30% in 25 patients and > or = 30% in 14 patients. Both the
      PGs at rest and the other Doppler parameters at peak exercise (PGs, SVHT, PGd)
      correlated with stenosis %. SVHT together with PGd on exercise Doppler
      represented the combination of two variables that was best for predicting a
      residual stenosis. When all three variables obtained by exercise Doppler were
      combined, every patient with residual stenosis was correctly identified. In
      particular, the combination (PGs > or = 28 mmHg + SVHT > or = 108 msec + PGd > or
      = 8 mmHg) identifies all patients with stenosis > or = 30%, while the combination
      (PGs < or = 38 mmHg + SVHT < 108 msec + PGd < 10 mmHg) excluded those with
      significant stenosis. CONCLUSION: Parameters obtained from the transisthmic
      gradient (PGs, SVHT, PGd) measured at peak exercise by CW-Doppler can diagnose a
      residual stenosis % in operated AoCo. We propose using this noninvasive method of
      identifying patients who need to be referred for MRI.

PMID- 9616852
TI  - Coronary artery inflammation and thrombosis in Wegener's granulomatosis
      polyarteritis nodosa overlap syndrome.
AB  - Coronary arteries are frequently involved in systemic arteritis. The inflammatory
      infiltrate damages the intima and may trigger the occurrence of coronary
      thrombosis. We report an extreme example of how intimal inflammation in multiple
      sites of a coronary tree with and without atherosclerosis may trigger coronary
      thrombosis, in an elderly female patient who died of a clinically unrecognized
      systemic autoimmune-inflammatory disorder with necrotizing arteritis. The
      clinical picture was dominated by abdominal symptoms (peritonitis and possible
      chronic hepatic disease), renal failure and pulmonary X-ray opacities. A precise
      clinical diagnosis was not formulated, and the patient died of cardiac arrest 15
      days after admission. Autopsy showed findings typical of Wegener's granulomatosis
      and of systemic arteritis with fibrinoid necrosis and multiorgan infarctions.
      Wegener's granulomatosis-polyarteritis nodosa overlap syndrome was pathologically
      diagnosed. Although there were no clinical signs of heart involvement, the
      coronary tree showed inflammation associated with multiple mural and occlusive
      thrombi. The atypical severe clinical presentation, the short course of the
      disease and the age of the patient probably contributed to the non proper
      clinical diagnosis. Old age does not preclude the occurrence of autoimmune
      disorders, whose course may be dramatically fatal. The abrupt occurrence of a
      systemic disease with renal failure, hepatomegaly, lung opacities and serositis
      should prompt analysis to consider these disorders. If properly diagnosed,
      cardiac involvement should be suspected in autoimmune disorders, even when
      clinically silent or masked by the systemic clinical picture. In our patient, the
      role that heart involvement played in the outcome, if any, remains unknown, even
      though the postmortem pathological identification of coronary mural and occlusive
      thrombi is generally sufficient to attribute the final cause of death to coronary
      thrombosis itself.

PMID- 9616853
TI  - Cardiac rhabdomyosarcoma: a clinicopathologic and electron microscopy study.
AB  - A 66-year-old woman was admitted to the hospital with a neurological syndrome
      characterized by ataxia and diplopia. Magnetic resonance of the brain documented
      an ischemic medullary lesion. Examination of the heart revealed a grade 2/6
      systolic murmur at the left sternal border and apex that radiated towards the
      axilla. The echocardiography study showed a mild mitral regurgitation, and an
      abnormally enlarged posterior papillary muscle was found in the left ventricle.
      Two weeks after admission, the patient died suddenly due to a stroke. At autopsy,
      a recent vast swollen ischemic cerebral infraction was found. Furthermore, two
      old infarcts were observed in the spleen. A cardiac examination showed a white
      gray ulcered mass in the left ventricle and histological analysis revealed a
      rhabdomyosarcoma.

PMID- 9616854
TI  - [Acute disfunction from thrombosis of a prosthetic mitral valve: thrombolysis
      with rt-PA in the clinical emergency phase].
AB  - Prosthetic valve thrombosis can determine different degrees of valvular
      insufficiency or obstruction, with a potentially fatal course. The current
      literature has not established whether the best treatment is thrombolysis or
      surgery (thrombectomy or valvular replacement). However, both treatments expose
      the patient to the risk of serious sequelae or death. Here we describe a case of
      acute thrombosis in a prosthetic mitral valve. At presentation, the patient was
      in pulmonary edema and had a low cardiac output. She was treated with recombinant
      tissue-type plasminogen activator infusion (rt-PA 100 mg in 2 hours). Both
      clinically as well as echocardiographically, we observed a quick regression of
      the obstruction, but after the treatment, the patient developed an ischemic
      stroke with aphasia and hemiplegia. The authors conclude that thrombolysis is a
      highly effective treatment in resolving prosthetic thrombosis. However, because
      it carries a significant risk of embolization, it should be limited to patients
      with hemodynamic deterioration in whom surgery could also entail a significant
      risk of death.

PMID- 9616855
TI  - [Death conference: hindsight in heart surgery].
AB  - We report eight cases of death or decerebration occurred during major
      cardiothoracic surgery. The technical aspects that contributed to the failure are
      analyzed on the basis of the Italian Criminal Code (art. 43). When this type of
      event occurs, a case review frequently identifies failure to take action or
      imprudent behavior. The informed consent regulation currently in force may be
      helpful in identifying and following the most prudent conduct for the patient.
      The "death conference" should be a formalized and binding instrument for hospital
      accreditation.

PMID- 9616856
TI  - [ISO 9000: guidelines for a total quality system in health].
AB  - The Italian National Health System has recently been revised and reorganized. In
      the new scenario, the quality of the service being provided is considered
      extremely important. The international ISO 9000 standard has made it possible to
      implement a total-quality management system that can be documented and certified
      independently by a third party. Several hospitals in Italy and abroad have
      implemented a total-quality system according to ISO 9000 standards in order to
      provide a service that can satisfy the expectations of the patients in a
      controlled and efficient way. This article describes ISO 9000, proposes its
      application to ensure quality in the structures and organizations involved in the
      national health system and reports several examples of how the standard has been
      implemented in hospitals.

PMID- 9616857
TI  - [Minimum requirements, accreditation, certification, quality: connections and
      problems. An editorial comment on "ISO 9000: guidelines for a total quality
      system in health"].

PMID- 9616858
TI  - [Treatment of hypercholesterolemia in secondary prevention. Statement of the
      Italian National Association of Hospital Cardiologists].

PMID- 9616859
TI  - [A chart of post-acute myocardial infarct risk: results in the first 18 months of
      the GSSI follow-up study].

PMID- 9616860
TI  - [Primary and secondary prevention of ischemic cardiopathy. A meta-analysis with
      meta-regression as a biologic mechanism: reflections on clinical practice based
      on scientific evidence].

PMID- 9616861
TI  - Three-dimensional reconstruction techniques applied to intracoronary images.
AB  - In recent years, systems for the three-dimensional (3-D) reconstruction of
      intravascular ultrasound (IVUS) images have been developed. As a major advantage
      over conventional two-dimensional IVUS, 3-D IVUS offers longitudinal views of the
      reconstructed segments and provide more comprehensive insight into the spatial
      distribution of vascular structures. The present article is an overview of
      current 3-D reconstruction techniques. In particular, we discuss the sequence of
      basic steps required to obtain a 3-D reconstruction: IVUS image acquisition,
      digitization, segmentation and reconstruction. We also illustrate the different
      systems of 3-D reconstruction that are currently available. Some of them can be
      used on-line during surgical procedures, while others are more suited for off
      line applications and are useful research tools.

PMID- 9616862
TI  - [Antithrombotic therapy for unstable angina in non-q myocardial infarct].

PMID- 9616863
TI  - [The domino transplant and afterload mismatch].

PMID- 9616864
TI  - [The death of Giacomo Leopardi: chronic pulmonary heart].

PMID- 9616865
TI  - The social accountability of health professions institutions.

PMID- 9616866
TI  - The allied health professions in the twenty-first century.

PMID- 9616867
TI  - International perspectives on health education and training for allied health
      professionals.

PMID- 9616868
TI  - Transatlantic cooperation: using a consortial approach to enhance health
      professions education and practice.
AB  - In summary, consortial arrangements are excellent mechanisms to centralize
      operations, serve as a central clearinghouse for international information,
      increase communication, and create greater efficiencies in the exchange process.
      The outcomes of our initial experiences with the consortial arrangement indicate
      a great deal of satisfaction among students and faculty.

PMID- 9616869
TI  - Establishing health and human service professional education in the former Soviet
      Union: the Georgia to Georgia project.

PMID- 9616870
TI  - Use of an international faculty/student exchange program as a process to
      establish and improve graduate education and research within an allied health
      discipline.
AB  - It has been recognized in the allied health professions that allied health
      disciplines must enhance and increase their research and scholarly activity. If
      faculty/staff are to be judged in the academic environment in which they work,
      their efforts to conduct research must be supported. Recognition for academic
      scholarship measured by the performance of research and scholarly activity is
      often difficult for faculty/staff to attain because of increased demands for
      scheduled time devoted to classroom instruction and student advising. This
      inability for faculty/staff to engage in research and scholarly activity often is
      enhanced by the lack of proper and adequate facilities and equipment. Also
      important is the role of graduate education, which itself, provides a stimulus
      for the performance of research and scholarly activity. This article reports
      outcomes achieved by an international faculty/staff-student program that provides
      an opportunity for faculty/staff and students within an allied health discipline
      to conduct research and scholarly activity. This program could serve as a model
      to identify the strengths and benefits that can be achieved by such programs.
      This program is capable of improving the research and scholarly activity of all
      academic units within an allied health discipline.

PMID- 9616871
TI  - Creating a global society: the Neumann-Danang connection.

PMID- 9616872
TI  - DHNet: a model for international research collaboration.
AB  - Internet technology has changed the way information is accessed, shared, and
      stored. This technology has supported the growth of scientific networks based on
      the need for improved communications and a team approach to problem solving.
      Scientists throughout the world are now able to come together in "virtual
      laboratories" or "collaboratories" to conduct research, analyze data, and discuss
      findings in a more timely and cost-efficient manner. The DHNet is based on a
      collaboratory model. It is a Web-based Internet resource designed to encourage
      research collaboration among dental hygiene professionals without regard to
      geographic location. The DHNet creates an electronic infrastructure that
      facilitates the linking, relating, and clustering of concepts that are critical
      to advancing a body of knowledge. It also creates a new standard for placing
      information on the Internet, which currently lacks conventions and structures for
      knowledge management. Designed to be maintained by its users with minimal staff
      support, the DHNet provides a mechanism for electronic publication of clinical
      observations, research, research in progress, and other document/media types.
      DHChat, the discussion forum component, provides an electronic communications
      tool for discussing topics of interest, research questions, and ways in which
      researchers would like to work together. Depending on the nature of the
      investigation, multi-site studies can be conducted or researchers can be
      responsible for different aspects of the same study. Video conferencing from
      desktop computers now permits synchronous discussion, enabling participants to
      see each other and work on the same document. The purposes of this article are to
      discuss the design of the DHNet as a model for supporting international research
      collaboration, and to discuss issues related to the use of electronic technology.

PMID- 9616873
TI  - Neurological rehabilitation in Indonesia and the UK: differences and
      similarities.
AB  - Both countries face considerable challenges to their rehabilitation services.
      Although contextually different, the problems and challenges are common to both.
      Two contrasting views of disability have been presented. In the UK disability may
      be viewed as a disaster, while in Asia illness and disability may be viewed as
      inevitable. Personal independence is not a universal goal of rehabilitation,
      because in some cultures dependence on others is an expected consequence of
      disability. Disability in Indonesia translates into a large burden of care for
      the family, whereas English families may expect greater help from the government
      in caring for their relative. Western rehabilitation is increasingly patient
      directed, whereas the Indonesian model is more likely to be determined solely by
      professionals. The problems observed by the team in Indonesia were remarkably
      similar to those experienced in the UK. A patient centered goal setting approach
      can be considered vital to neurological rehabilitation, although the focus of the
      goals set is likely to be very different in these two cultures. The fundamental
      importance of a multidisciplinary team is recognized in both cultures, although
      team working may not be easy in either situation. Managerial commitment is
      essential for the survival of a team, yet both structures sometimes fail to
      provide the necessary support. Hierarchical leadership can inhibit team
      development both in the UK and in Indonesia, as can frequent rotation of staff.
      Prescription of therapy by doctors inhibits the development of therapists in both
      cultures, and therefore the overall effectiveness of the team. In both the UK and
      Indonesia, the value of rehabilitation as a specialty is not widely recognized.
      The absence of life and death situations means that services are often out of the
      public eye, and poorly understood. However, the prevalence of disability will
      increase the need for rehabilitation services worldwide. Many challenges remain
      in both the UK and Indonesia to the development of more effective rehabilitation
      services. Issues like the lack of recognition of rehabilitation as a specialty,
      the importance of team work, the paucity of managerial support, and increasing
      demand for rehabilitation services will need to be recognized and addressed.
      Despite the different approaches to disability in the two cultures, the problems
      faced are similar. These problems will need to be solved if there is to be
      significant progress in this multidisciplinary field.

PMID- 9616874
TI  - Detection of complement C1q receptors on human spermatozoa.
AB  - Clq, the first component of the classical complement pathway, is known to play
      roles in promoting phagocytic events, in addition to its role in activation of
      complement. Although the molecular events in fertilization leading to the
      entrance of the spermatozoan into the egg are not well understood,
      ultrastructural observations suggest that the process is quasi-phagocytic in
      nature. There is increasing evidence that complement components might play roles
      in fertilization. Previously, we have shown that C1q promoted the agglutination
      of capacitated human sperm as well as their adhesion to zona-free hamster eggs.
      In the present experiments, human spermatozoa were solubilized and, following
      their phase separation in Triton X-114, subject to 1-D polyacrylamide gel
      electrophoresis and immunoblotting for the presence of C1q receptors. Both gC1q-R
      and cC1q-R were detected. In addition, the ability of C1q to promote sperm
      agglutination was shown to be dependent upon capacitation, suggesting the
      increased expression of C1q receptors during this process.

PMID- 9616875
TI  - Immunity to vaginal infection by herpes simplex virus type 2 in adult mice:
      characterization of the immunoglobulins in vaginal mucus.
AB  - Progestin-treated female mice are susceptible to vaginal infection by two
      sexually transmitted disease organisms: herpes simplex virus type 2 (HSV-2) and
      Chlamydia trachomatis. Vaccination of mice with HSV-2 or chlamydial antigens
      elicits immunity to vaginal infection that may be due in part to secreted
      antibodies in the vaginal lumen. Analysis of the role of these antibodies in
      immunity would be aided by information about the vaginal secretion in progestin
      treated mice and the antibodies it contains. Gross and histologic observations of
      progestin-treated mice that were immune to vaginal HSV-2 infection indicated that
      the vaginal lumen was filled with mucus. A procedure for extraction of
      immunoglobulin from the mucus was developed and shown to recover at least 98% of
      the secretory IgA (S-IgA) that was free to diffuse from the mucus. Immunoblotting
      revealed that the predominant molecular form of IgA in vaginal mucus was dimeric
      S-IgA. Immunoglobulin concentrations in vaginal secretions were higher in immune
      mice than in non-immune mice and S-IgA concentrations were higher than those of
      IgG. The IgG concentration in vaginal secretions of immune mice was 4.5-fold
      higher than in non-immune mice, while serum IgG increased only 1.5-fold,
      suggesting local production of IgG or increased transudation in immune mice.
      Specific IgG antibody to HSV-2 was demonstrated in vaginal secretions of immune
      mice at a mean ELISA titer of 6200, whereas the titer of specific S-IgA in the
      same secretions was only 1.9. Thus, while the predominant immunoglobulin by
      weight in the vaginal mucus of immune mice was S-IgA, the ELISA titers suggested
      that the virus-specific antibody was almost entirely IgG.

PMID- 9616876
TI  - Docosahexaenoic acid, a constituent of fetal and neonatal serum, inhibits nitric
      oxide production by murine macrophages stimulated by IFN gamma plus LPS, or by
      IFN gamma plus Listeria monocytogenes.
AB  - Murine macrophage activation is deficient in the fetus and the neonate, and in
      areas of the placenta perfused by the fetal circulation. Fetal and neonatal serum
      concentrations of docosahexaenoic acid (DHA) are 150 microM, or approximately 50
      fold higher than in the adult. We previously showed that DHA inhibits activation
      of the gene for inducible nitric oxide synthase (iNOS) in murine macrophages
      stimulated in vitro with interferon gamma (IFN gamma) plus lipopolysaccharide
      (LPS). We have now pursued these observations in greater depth. An assay system
      was developed which separated the stimulation of macrophages by IFN gamma plus
      LPS, and the actual production of nitric oxide (NO). It was found that
      macrophages do not produce NO until they have been stimulated by IFN gamma plus
      LPS for a period of 10 h. NO is produced during the subsequent 10 h, even though
      IFN gamma plus LPS are not longer present. DHA, if present, inhibited only during
      the initial 10 h stimulation; DHA did not inhibit the production of NO by
      macrophages which had previously been stimulated by IFN gamma plus LPS, and were
      already producing NO. It was also found that DHA was less inhibitory if given
      prior to the IFN gamma plus LPS stimulation. In a dose-responsive manner, DHA
      inhibited the increased abundance of iNOS mRNA by macrophages stimulated by IFN
      gamma plus LPS. NO contributes to the host defense against Listeria monocytogenes
      and other intracellular pathogens. We therefore investigated the ability of DHA
      to inhibit NO production by macrophages stimulated by IFN gamma plus Listeria
      monocytogenes in vitro; DHA inhibited transcription of the iNOS gene and also the
      listeriocidal activity of activated macrophages. Inhibition of NO production by
      DHA may contribute to the increased susceptibility of the fetoplacental unit and
      neonate to intracellular infections.

PMID- 9616877
TI  - A promoter mutation in the tumor necrosis factor alpha gene is not associated
      with preeclampsia.
AB  - Preeclampsia is associated with increased plasma concentrations of tumor necrosis
      factor alpha (TNF alpha) and TNF receptors. A mutation in the promoter region of
      the TNF alpha gene (TNF T2) has been described which is associated with increased
      transcription of the gene. Due to the familial predisposition of preeclampsia, we
      hypothesized that this promoter mutation in the TNF alpha gene may contribute to
      the genetic etiology of preeclampsia. Our objective was to determine the allele
      frequency of this mutation in a population with well-characterized preeclampsia
      and with hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome as
      compared with normotensive controls. DNA was extracted from blood of 131 women
      with severe preeclampsia, 75 women with HELLP syndrome, and 41 normotensive
      gravid controls. Genotypes were determined using the polymerase chain reaction
      (PCR), allele-specific restriction with Nco1, and agarose gel electrophoresis.
      Results were analyzed with a chi 2 contingency table. No significant differences
      were found between patients with severe preeclampsia, HELLP syndrome,
      normotensive gravid controls, and previously published allele frequencies. The
      frequency of the TNF T2 allele is not increased in patients with preeclampsia or
      HELLP syndrome. Therefore, this promoter mutation is probably not a major genetic
      cause of preeclampsia. As more genes are cloned, sequenced and localized, this
      will enable investigators to take this 'candidate gene approach' to investigate
      potential genetic causes of preeclampsia.

PMID- 9616878
TI  - Decrease in the proportion of granulated CD56+ T-cells in patients with a history
      of recurrent abortion.
AB  - We investigated levels of CD56+ T-cells (CD3+ CD56+ cells) in peripheral
      circulation, which express one of the natural killer (NK) cell markers, by flow
      cytometry and with monoclonal antibodies in patients with a history of recurrent
      abortion. We compared these values with those obtained in normal women who were
      not pregnant as well as in normal pregnant subjects. The percentage of CD56+ T
      cells in the peripheral blood of patients with a history of recurrent abortion
      was less than that in the non-pregnant or pregnant women. These results suggest
      that CD56+ T-cells with extrathymic properties may be associated with the
      maintenance of normal pregnancy in humans.

PMID- 9616879
TI  - Antiphospholipid antibodies and reproductive outcome: the current state of
      affairs.
AB  - Antiphospholipid antibodies were first linked to pregnancy loss more than 20
      years ago, and the condition known as antiphospholipid syndrome is perhaps the
      most convincing 'immunologic' disturbance other than anti-erythrocyte and anti
      platelet alloimmunization disorders. Specific criteria for the antiphospholipid
      syndrome have been delineated, the anticardiolipin assay has been standardized,
      and authorities agree on laboratory criteria defining lupus anticoagulant.
      Nonetheless, considerable confusion exists regarding antiphospholipid syndrome
      and related reproductive problems. The state of affairs primarily derives from
      two problems: the first is the premature introduction of non-standardized
      antiphospholipid assays into clinical use without rigorous standardization and
      prior to convincing proof of clinical utility. As a result, well-intending, but
      less well-versed clinicians sometimes make the diagnosis of antiphospholipid
      syndrome in women who are negative for lupus anticoagulant and anticardiolipin
      antibodies. This is especially confusing in the face of of growing evidence that
      the relevant in vivo antiphospholipid antigen is formed by a complex between beta
      2-glycoprotein 1 and phospholipids. A second major problem is that of unwarranted
      discrepancies in the clinical and laboratory features of patients considered to
      have a diagnosis of antiphospholipid syndrome. This problem is most apparent in
      the case selection for pregnancy-loss treatment series and trials. Many series
      have included women with predominantly pre-embryonic and embryonic pregnancy
      losses, while others included a large majority of patients with one or more
      second or third trimester pregnancy losses. Some treatment trials purposefully
      excluded patients with a history of thrombosis or systemic lupus erythematosus,
      features found in nearly 50% of patients in other series. Though most authorities
      require the presence of either lupus anticoagulant or medium-to-high titer IgG
      anticardiolipin antibodies to make a diagnosis of antiphospholipid syndrome, in
      some series no more than half of the study patients had lupus anticoagulant and
      as many as 20% had only IgM anticardiolipin antibodies. It is very unlikely that
      patients with such disparate clinical and laboratory findings have the same
      autoimmune syndrome, and a stated or implicit diagnosis of antiphospholipid
      syndrome in such a wide variety of women is scientifically unsound and clinically
      dangerous. The relationship between antiphospholipid antibodies and poor
      reproductive outcomes must be approached through rigorous scientific study and
      appropriate treatments established by well-designed clinical trials.

PMID- 9616880
TI  - [Biology of osteoclasts; their role in bone metastases].
AB  - Bone is a common site for metastasis of malignant tumors. These can be recognized
      radiologically as either lytic or sclerotic lesions since the tumor cells
      stimulate resident bone cells to cause excessive local resorption or new bone
      formation. The osteoclast, as the only cell being capable of resorbing bone, is
      of major importance for the homing of tumor cells in bone and progression of
      metastasis due to bone destruction. Thus, the improvement of our means of
      therapeutic intervention towards prevention of tumor progression and pathological
      fractures will depend on our better understanding of both the molecular basis of
      bone resorption and the cellbiology of the osteoclast. This article presents our
      current opinion of the molecular mechanisms of bone resorption by the osteoclast.
      After describing the morphological features of the osteoclast, aspects such as
      cell mobility, attachment, enzymes synthesis, transmembrane transport, osteoclast
      differentiation and function, as well as the protooncogenes c-src and c-cbl and
      their role in bone resorption are presented in detail.

PMID- 9616881
TI  - [Radiologic diagnosis of bone metastases].
AB  - Metastases are the most common malignant tumors of the skeleton. Several imaging
      modalities can be engaged for the diagnosis of skeletal metastases. They may be
      combined, depending on the individual clinical setting. Plain films are used for
      evaluation of symptomatic regions of the skeleton. Sensitivity is low, but benign
      skeletal disorders causing clinical symptoms can usually be identified in plain
      films. Bone scintigraphy is employed for a survey of the entire skeleton with
      high sensitivity for the presence of metastases, but only poor specificity.
      Computed tomography (CT) and magnetic resonance imaging (MRI) are advanced
      diagnostic methods, essential particularly in the diagnosis of metastatic spinal
      disease. Using CT, additional percutaneous bone biopsies can be performed easily
      and safely. Of all imaging modalities, MRI has the highest sensitivity for
      skeletal metastases. Other advantages are the possibility of multidirectional
      slice positioning and excellent soft tissue contrast.

PMID- 9616882
TI  - [Biphosphonate therapy in the management of skeletal metastases].
AB  - Bisphosphonates are a new theraeutic option in the treatment of bone diseases.
      They inhibit osteoclastic bone resorption and are established in the treatment of
      osteoporosis, Paget's disease of bone and especially in tumor bone disease. The
      effects of pamidronate, clodronate and ibandronate in the treatment of
      hypercalcemia of malignancy and osteolytic bone disease have been extensively
      studied. These drugs represent the treatment of choice in hypercalcemia of
      malignancy. The regular application of bisphosphonates reduces skeletal-related
      events like pathologic fracture, bone pain or hypercalcemia of malignancy,
      especially in breast cancer and multiple myeloma. Of great interest are the
      ongoing studies concerning prophylactic application of bisphosphonates in tumors
      bearing a high risk for bone metastases, especially since the first results
      suggest a significant reduction in the development of bone metastases in breast
      cancer patients.

PMID- 9616883
TI  - [Systematic hormone- and chemotherapy in the management of skeletal metastases].
AB  - Bone is among the most common sites of metastatic disease in cancers of the
      breast, prostate, and lung. The decision about systemic therapy depends on the
      histology, presence and extent of extraskeletal disease, and the performance
      status of the patient. For patients with estrogen-receptor-positive breast cancer
      or prostate cancer, hormonal treatment represents the treatment of choice. In
      estrogen-receptor-negative breast cancer, and for patients who have failed
      hormonal therapy or have liver metastases, chemotherapy should be initiated. All
      patients with small-cell lung cancer should receive chemotherapy. Bone metastases
      of differentiated thyroid cancers can be treated with radioisotopes. In non-small
      cell lung cancer or renal cell cancer, systemic chemotherapy should be confined
      to younger patients and patients in good general condition. Radiologic assessment
      of responses of skeletal metastases to systemic therapy is often difficult. New
      approaches in measuring bone metabolites in urine might prove helpful.

PMID- 9616884
TI  - [Topical radiotherapy in the management of skeletal metastases].
AB  - Local radiotherapy plays an important role in the palliative management of bone
      metastases. Different concepts of dose fractionation are in use. A judgement of
      the efficacy of these concepts should be based on their different palliative
      treatment endopoints. The efficacy of radiotherapy using published data can be
      analysed with respect to pain relief and re-establishment of bone integrity as
      treatment endopoints. Trials stratifying radiooncological techniques according to
      an optimization of quality of life are missing. Nevertheless, the rationale for
      individual treatment in daily work is based on systemic tumor extent, life
      expectancy, the kind of symptoms and the location of the metastasis in question.
      In patients with reduced live expectancy a remarkably high chance of pain relief
      (70%) could be achieved with single doses of 8 Gy. The latency period until pain
      relief is shorter with higher single doses. In case of recurrence of pain
      reirradiation with a single dose results in an equally high response rate.
      Patients with a solitary metastasis, patients with longer live expectancy and
      patients with pathological fractures should be treated with 'curative' doses,
      aimed to cause maximum tumor cell killing. Impaired bone stability in patients
      who are not suitable for surgical intervention requires orthetic supply. Apart
      from the effect of pain relief, remineralization is the important treatment goal
      for these patients. Conventional radiotherapy with doses of 40-50 Gy resulted in
      remineralization in 60-80% of the patients 4-8 weeks after irradiation.
      Remineralization could not be acceierated by short course fractionation courses.

PMID- 9616885
TI  - [Arthroscopy of rarely affected joints. Current status].

PMID- 9616886
TI  - [30 years' experience with posterior fundoplasty in the treatment of
      gastroesophageal reflux (analysis of 1499 cases)].
AB  - Posterior fundoplasty, is an antireflux procedure we introduced in 1966 after
      experimental laboratory trials and published in 1969. To data, we have operated
      more than 2,000 cas. Although we now also use laparoscopic procedures, the
      present study reports our experience with 1499 patients who underwent the
      conventional procedure and who have been followed for 4 to 30 years. Mortality
      has been nil and mean failure rate was 9.6%. One important feature of this
      technique is the low incidence of undesirable effects: 3.66% dysphagia (none
      required dilatation), 3.94% impossibility to vomit, and 4.94% difficulties in
      belching. This study establishes comparisons between this group of 1499 patients
      and another group of 68 patients who underwent the original Nissen procedure
      performed under laparoscopy by the same surgeon and followed for a similar
      period. Such a larger personal series followed for 30 years is rare in the
      medical literature.

PMID- 9616887
TI  - [A new technique of splenic preservation: extraperitoneal transposition of the
      traumatized spleen].
AB  - The lifelong risk of overwhelming infection after splenectomy is well recognized.
      Although children are at greater risk, adults are clearly vulnerable. This is an
      incentive to safely preserve the spleen in splenic injuries. Nonoperative
      management and use of different surgical techniques and synthetic materials to
      stop bleeding have been experienced and reported. They have the major advantage
      of spleen mass preservation and prevention of splenectomy complications: but also
      some disadvantages, for instance: prolonged hospital stay and subdiaphragmatic
      collection or delayed spleen rupture. This has prompted us for splenic salvation
      without any attempt to stop bleeding by transposition of spleen into an
      extraperitoneal cavity created surgically. During a 4 year period (from the end
      of 1989 to the fall of 1993) ten trauma patients were treated with this original
      technique. All of these patients had a definitive indication for emergency
      laparotomy. The procedure was successful in all patients without any unexpected
      complication.

PMID- 9616888
TI  - [Pneumatosis cystoides of the colon. Apropos of 7 cases].
AB  - Seven cases of pneumatosis cystoides intestinalis affecting the colon (PKC)
      revealed 5 times by a nonspecific symtomatology and 2 times by an occlusion were
      reported. In three of the patients the disease was found as a primary idiopathic
      form free of clinical antecedents. In 4 of the patients the pneumatosis was found
      to be secondary to a pulmonary disease, a gastric ulcer, a connectivite of a
      corticotherapy. The PKC was generally diagnosed either by barium enema or by
      computed tomography and less frequently by colonoscopy with deep biopsy allowing
      differential diagnosis with colonic polyposis. The mechanism and etiology of the
      PKC were not fully understood. The illness is a benign condition that often
      responds to a conservative management--i.e. abstention, oxygenotherapy, diet or
      antibiotherapy- or exceptionally to surgical colonic resection in case of acute
      complication.

PMID- 9616889
TI  - [Hepatic resections in the treatment of hepatocellular carcinoma].
AB  - Treatment of hepatocellular carcinoma has become multidisciplinary. Liver
      resection, when technically feasible, remains the procedure of choice for non
      cirrhotic patients. On the contrary, its indications are decreasing for
      cirrhotics with the emergence of interventional therapies and since selected
      patients with small tumors and sufficient life-expectancy have become candidates
      to liver transplantation. Better results have to be obtained by adjuvant
      therapies in order to decrease the propension of the hepatocellular carcinoma to
      recur inside the liver. Intraarterial injection of lipiodol iodine-131 seems to
      give encouraging results in reducing the local recurrence rate after liver
      resection.

PMID- 9616890
TI  - [Possibilities of anterior approach to the lumbar spine by minimal
      retroperitoneal access. Anatomical bases. Technical principles and initial
      results].
AB  - Anterolateral approach to the lumbar spine using a retroperitoneal approach is a
      common technique. But conventional approaches are performed laterally, resulting
      in parietal muscular damage, which may alter functional results. The authors
      present their experience about a minimized pararectal retroperitoneal approach
      from T12 to S1. Some anatomical aspects are important for a safe and reproductive
      procedure. The authors used mainly this technique in association with posterior
      correction and fixation in traumatic and degenerative pathologies. They point out
      the simplicity of this technique which is performed without special equipment. It
      seems a real alternative to laparoscopic techniques and micro-surgical antero
      lateral interbody fusion, especially because of minimal potential complications
      and low post operative morbidity.

PMID- 9616891
TI  - [Serum and urine prostate-specific antigen ratio: its value in the distinction
      between prostate cancer and adenoma when serum prostate-specific antigen level is
      between 4 and 10 ng/ml].
AB  - BACKGROUND: In an earlier study, we demonstrated that benign prostatic
      hyperplasia (BPH) was associated with significantly higher urine levels of
      prostate-specific antigen (PSA) than in prostate cancer (PC). These early results
      led to the present study: we assessed, in patients undergoing a prostate biopsy,
      the clinical value of the PSA serum/urine ratio (PSA S/U) in patients for the
      differential diagnosis of PC, particularly when the pre-biopsy serum level of PSA
      lies between 4.0 and 10.0 ng/ml. METHODS: All patients without an indwelling
      drain who underwent transrectal echoguided biopsy were prospectively included in
      this study from November 1994 to December 1995. All serum and urine PSA
      measurements were done by the same laboratory using a Tandem R kit (Hybritech).
      Blood and urine samples were obtained during the 24 hour period prior to surgery
      during which all urethral or rectal manipulation was avoided. RESULTS: We studied
      130 patients with BPH (n = 73) or PC (n = 57). The PSA serum levels and the PSA
      S/U were significantly different between the BPH and the PC groups. In the
      subgroup of 50 patients with a serum PSA level in the 4-10 ng/ml range, the
      difference between the BPH and PC patients was not significantly different except
      for the PSA S/U ratio. Receiver operating characteristic (ROC) curves showed that
      the diagnostic power of PSA S/U was greater than serum PSA. CONCLUSION: These
      results suggest that the PSA S/U ratio could be useful to distinguish between BPH
      and PC, particularly when diagnosis is uncertain in patients whose serum PSA is
      in the 4.0-10.0 ng/ml range.

PMID- 9616892
TI  - [How many abdominal hysterectomies can be avoided by laparoscopic surgery?].
AB  - Laparoscopic hysterectomy performed for benign uterine lesions without prolapse
      is becoming more and more popular. This surgical route has some of the advantages
      of the vaginal route and could avoid numerous abdominal hysterectomies. Our
      experience shows that most of abdominal or laparoscopic hysterectomies could be
      done using the vaginal route which is for us the reference. One question about
      laparoscopic hysterectomy is: can we perform this technique to avoid abdominal
      hysterectomy when the vaginal route looks impossible? To answer this question, we
      retrospectively studied 171 hysterectomies. The laparoscopic hysterectomy rate
      should not reasonably exceed 10 to 15%, yet is much higher for the promotors of
      this technique of which advantages compared with vaginal hysterectomy are not
      clearly demonstrated.

PMID- 9616893
TI  - [Thyroid nodules associated with Graves' disease: another argument for surgical
      treatment].
AB  - Much controversy surrounds the incidence of thyroid cancer associated with
      Graves' disease. We studied retrospectively 110 patients operated on for Graves'
      disease between 1991 and 1996. Each patient was evaluated by clinical exam,
      biological test, ultrasonography, and scintigraphy. No patient had a history of
      prior external radiation to the head or the neck. All patients underwent near
      total or total thyroidectomy. Nodules in the thyroid were detected in 28 cases: 6
      were papillary carcinoma (5.5% from patients with Graves' disease, and 21.4% from
      patients with Graves' disease associated with thyroid nodules). These data
      suggest interest of surgery in Graves' disease associated with thyroid nodules.

PMID- 9616894
TI  - [Technique for protecting the liver graft less tolerant than the small bowel to
      heat-induced ischemia in experimental liver + small bowel transplantation in
      swine].
AB  - Multivisceral and orthotopic liver/small bowel transplantations have been
      performed to treat patients with intestinal failure associated with liver failure
      induced by parenteral nutrition. The aim of this experimental study was to
      determine the experimental liver-small bowel harvesting and transplantation
      technique that achieves the best compromise between liver and intestine ischemia
      times in pigs. Initial portal revascularization of the liver which reduces the
      hepatic warm ischemia time after cold ischemia preparation of the graft immersed
      in lactated ringer's solution at 4 degrees C, reduce the risk of primary non
      function of the graft.

PMID- 9616896
TI  - [Value of screening of aortic aneurysms].
AB  - Among the causes of mortality observed in the elderly population between 65 years
      and 80 years, the specific mortality rate related to AAA has been rising for
      several years. The interest of screening programs has been demonstrated and
      elective surgery is likely to reduce the incidence of rupture in at risk
      patients. This prospective study will allow us to know the prevalence of AAA in
      our country. A screening program will be set up with general practitioners and
      elective surgery will be proposed according to the diameter of the aorta. Cost
      effectiveness of this program will be assessed. Improvement of life expectancy
      will be measured.

PMID- 9616895
TI  - [Evaluating the efficacy of a multidisciplinary approach of severe functional
      deficits].
AB  - Therapeutic indications aimed at improving function in handicapped persons are
      difficult to establish as the expected result of a given technique may vary. We
      have developed a multidisiplinary approach for handicapped persons. Our
      assessment of this activity which has concerned 62 patients from October 1995 to
      October 1996 is promising and encourages us to continue this type of attitude.
      Forty-six of the 58 persons evaluated stated they were well satisfied or very
      well satisfied with the management of their case and outcome was worse in none of
      the patients.

PMID- 9616897
TI  - [Mechanical vascular clips with an automatic stapler in reconstructive
      microsurgery. Apropos of 16 clinical cases].
AB  - From October 1995 through March 1997, we performed 30 microsurgical
      reconstructions and achieved microvascular anastomoses in 16 with an automatic
      stapler (VCS) which allows insertion of titanium clips in the everted vessel
      walls. The mean age of the patients (15 men, 1 woman) was 42 years. Mean vessel
      diameter of the donor and recipient sites was 2 mm for the arteries and 3 mm for
      the veins. Recipient vessels had suffered radiation damage in 3 cases. Micro
      anastomoses were performed in 26 cases, with end-to-end sutures in 24 and end-to
      side sutures in 2. There were 11 arterial procedures including 3 bypasses and 15
      venous procedures with 1 bypass. Peroperative thrombosis occurred in 2 cases and
      were treated by undoing the anastomoses and resuturing manually. There were no
      early or late postoperative vascular complications. This clinical experience
      confirms the advantages of this mechanical approach to microanastomotic
      procedures for small vessels as previously demonstrated in experimental work: a
      system avoiding transfixation, rapid procedure, reliability.

PMID- 9616898
TI  - [Aortoiliac surgery in chronic hemodialysed patients].
AB  - Thirty eight patients on chronic hemodialysis were operated on for treatment of
      complicated aortoiliac atherosclerosis: 31 had aneurysms and 7 had stenotic or
      obstructive lesions. The 35 male and three female patients ranged in age from 39
      to 78 years (mean: 55.3). The duration of hemodialysis treatment before the
      operation ranged from one month to 22 years but 80% of the patients were operated
      on during the first five years following the beginning of maintenance
      hemodialysis. The surgical repairs consisted of long aorta to femoral artery
      prosthesis in obstructive lesions and of short prostheses in cases of aneurysms
      so as not to make more difficult subsequent renal transplantation. All patients
      were operated on from 6 to 18 hours after a dialysis. Hemodialysis was resumed on
      the day of surgery in few patients or later according to the level of kalemia.
      Postoperative mortality rate was 10.5% and morbidity 13.5%. Only seven patients
      underwent secondary renal transplantation. The long-term survival rate was 43% at
      five years and 11% at ten years. Late deaths were due to coronary artery disease
      or to worsening of arterial lesions in the lower limbs.

PMID- 9616899
TI  - [Adrenal cystic tumors. Apropos of 8 cases].
AB  - We report eight cases of cystic lesions of the adrenal glands. Benign cysts or
      pseudocysts are the predominant tumors of the adrenal glands. However, neither
      tumor size, gross aspect, presence of calcified walls, color, cyst contents nor
      routine laboratory tests can exclude a malignant or hormone secreting lesion. We
      discuss the role of therapeutics, transparietal puncture and simple radiographic
      surveillance in the management of patients with cystic tumors of the adrenal
      glands. Surgery is often indicated or recommended.

PMID- 9616900
TI  - [Aneurysms of splanchnic arteries].
AB  - Aneurysms of splanchnic arteries represent an uncommon but important vascular
      disease, which many times presents itself as clinical emergency and often results
      in death. 11 patients with splanchnic aneurysms were treated in our Department
      during the last 15 years. These aneurysms were located in 5 cases in splenic
      artery, 4 cases in hepatic artery, 1 case in celiac axis and 1 case in right
      gastroepiploic artery. Surgical treatment of these aneurysms was successful in
      all but one patient (he died from rupture of a hepatic artery aneurysm). Giving
      an overall mortality similar to that reported in the literature. The treatment of
      these aneurysms is discussed, while literature about this uncommon disease is
      reviewed.

PMID- 9616901
TI  - [Original procedure of functional plasty of primary inguinal hernias].
AB  - We describe a novel autoplasty method we developed for primary inguinal hernia
      repair and report our results in nearly 150 operations. The method is based on
      novel principles: priority given to an individual stato-dynamic conception of the
      inguinal region; effect on physiological defense mechanisms of the inguinal
      canal; absence of tension on the sutures by autoplastic repair.

PMID- 9616903
TI  - [Plea for large excision of the thyroid gland in benign diseases (retrospective
      study 1986-1996)].
AB  - According to the literature and the study of 158 patients who have been examined,
      operated and analysed by the same medicosurgical staff, the authors have found a
      great frequency of clinical and echographic recurrencies. This frequency has also
      been found by others teams. The study of the different factors for goitrogenesis,
      either in multiplication of thyrocytes or tissular differentiation shows the
      pathogenic polymorphism. For the polynodular lesions, most of them located in the
      2 lobes, total thyroidectomy seems to be the only procedure to prevent
      recurrencies. For the nodular lesions, most of the time unilateral, recurrencies
      are due to the fact that infracentimetric lesions have not been detected by
      preoperative ultrasonography and scintigraphy. They are discovered by
      postoperative ultrasonography and the long time follow-up is not to this date
      sufficient. The palpation and the peroperative ultrasonographic verification of
      the remaining lobe seem to be the best attitude to avoid the growth of small
      undetected lesions.

PMID- 9616902
TI  - [Laparoscopic surgery of recurrent hernias after prosthesis (35 cases)].
AB  - We report 35 cases of laparoscopic repair after prosthesis surgery using the
      classic open technique (19 cases) or laparoscopic technique (16 cases). Most
      difficulties were observed after intraperitoneal laparoscopy. Hernia repair was
      preferentially intrapreperitoneal (31 cases). Post-operative morbidity was low
      with two cases of serohematic effusion treated by puncture. Mean hospital stay
      was 2.5 days. Patients returned to normal activity within 7 days but work
      stoppage in active patients depended more on patient motivation than the initial
      surgical procedure. There were no reiterative recurrences although follow-up is
      too short (mean 21.2 months) for definitive results.

PMID- 9616904
TI  - [Isolated mandibular metastases. Therapeutic strategy. Apropos of 7 cases].
AB  - Among the mandibular tumours, the secondary malignant tumours are uncommon. We
      relate 7 cases observed between 1977 and 1995. Two cases have revealed the
      original cancer (rectum, prostate). The five other cases were discovered during
      the evolution of the original cancer (colon, lung, kidney, thyroid, breast).
      These 7 mandibular metastases were isolated. The treatment included a mandibular
      resection in 6 cases. In one of these cases, the reconstruction was performed
      with a free vascularized fibular transplant with success. Among the seven cases,
      two patients are alive, at the present time, with a mean follow-up of 3 years.
      This justifies a curative treatment.

PMID- 9616905
TI  - [Flexible locked centromedullary osteosynthesis. Results of 125 cases of unstable
      cortical bone fractures of the tibia].
AB  - We present a series of 125 cases of centromedullary fixation with a flexible
      locked nail of unstable cortical bone fractures of the tibia in which we studied
      healing conditions in order to identify parameters which would predict the rate
      of consolidation. One hundred ten fractures followed more than 6 months were
      included in the statistical analysis. For 94 fractures, primary consolidation was
      achieved in a mean 11 weeks. Fractures situated in the lower portion of the tibia
      healed the fastest (10 weeks). However, opening the fracture site and comminutive
      fractures did not affect the rate of healing except for proximal fractures and
      for fractures with a gap exceeding 10 cm. These two parameters, width of the bone
      gap (whether trauma induced or iatrogenic) and proximal localization of the
      fracture were the cause of the cases with long periods of non-consolidation
      (14.5%). The speed of peripheral osteogenesis is considered to be accelerated
      with the flexible nail as seen in our 94 cases where no conversion was necessary.
      This method provides a mean 1 month gain over consolidation times compared with
      locked nailing where the distal locking probably increases the rigidity of the
      system.

PMID- 9616906
TI  - [Congenital generalized progressive ossifying myositis. Clinical case].

PMID- 9616907
TI  - [Reoperations of total hip prosthesis with acetabular reconstruction using bone
      allografts].
AB  - Detachment of the acetabular segment is the most important long-term problem with
      total hip prostheses. We analyzed long-term outcome in our first 48 acetabular
      reconstructions with cryopreserved allografts. Among the 48 hips operated on with
      this technique, 38 were reassessed after a mean follow-up of 7 years 3 months
      (range 5 years-9 years 6 months). Mean age of the population at surgery was 63
      years. There were two predominant etiologies: sequelae of chronic hip luxation
      and primary osteoarthrosis of the hip. In 10 cases with massive destruction, the
      Muller ring was used to stabilize the allograft. Results were assessed at 6
      months, 2 years, 4 years and at longest follow-up using the Merle d'Aubigne
      clinical assessment scale. For the radiographic assessment, the Ranawat criteria
      were used to evaluate the alignment of the reconstruction. Clinically, patient
      comfort was improved in all cases with significant pain relief. Radiologically,
      mean acetabular ascention was 5 mm and mean medialization was 3.5 mm. A rim was
      observed in 24 cases including 19 measuring less than 2 cm. Acetabular loosening
      was evidenced in the 5 other cases where the rim measured more than 2 mm. In 4 of
      these 5 cases, the acetabulum had migrated to a new setting. The radiographic
      image then remained unchanged. Analysis of our 38 first cases showed that bone
      allografts with cimented acetabulum, sometimes with a stabilizing ring, is one of
      the possible solutions for difficult acetabular reconstructions. However, after a
      7 years 3 months follow-up, we have had five (13%) aseptic displacements
      including one case requiring reoperation. In the 33 stable joints (87%) with good
      results reconstruction has achieved a nearly perfect anatomic position, similar
      to first intention arthroplasty with the use of perfectly stabilized bone grafts
      with a maximal acetabular surface. Our follow-up is longer than most published in
      the literature. However, the migration rate of 13% it is still too short to draw
      any conclusion concerning the long-term outcome in our patients, despite their
      older age and reduced physical activity compared with primary hip arthroplasty
      patients.

PMID- 9616908
TI  - [Traumatic and iatrogenic lesions of abdominal vessels].
AB  - Gravity of abdominal vessels traumatisms is secondary to multiple factors. It
      depends on the type of injured vessels, aetiology and associated lesions. Between
      September 1984 and March 1995, 22 abdominal vessel traumatisms in 16 patients
      (mean age: 39 years) were treated. At surgical exploration, 4 aortic and 2 renal
      vein lesions, 7 iliac artery and 3 renal artery contusions, 2 superior mesenteric
      artery dissections; 3 infra-renal vena cava ruptures and 1 superior mesenteric
      vein dilaceration were found. All lesions were caused by penetrant wounds
      secondary to firearm or blade injury or secondary to injuries due to ski or
      traffic accidents. In 5 cases, lesions were iatrogenic. There was no mortality in
      the post-operative period, 14 patients out of the 16 patients operated on have
      been followed during a period from 1 to 120 months.

PMID- 9616909
TI  - [Structure and functions of the endothelium].
AB  - The vascular endothelium is a dynamic interface between blood and tissues, which
      releases vasoconstrictors or vasodilators regulating the vascular tone. The
      endothelium modulates the balance between thrombosis and haemorrhage. Activated
      endothelium may produce tissue factor which triggers the coagulation cascade. In
      different tissues, the endothelial cells become specialised and may participate
      to the immune response and inflammation. Various metabolic or immune stimuli may
      alter endothelial cell functions, induce leukocyte adhesion through expression of
      specialised molecules and modify the release of fibrinolytic agents, cytokines,
      and growth factors.

PMID- 9616910
TI  - [Endothelium, thrombosis and fibrinolysis].
AB  - Vascular endothelium is involved in the control of thrombosis by influencing
      among other things, platelet functions, coagulation and fibrinolysis.
      Fibrinolysis is due to plasminogen conversion into plasmin by activators, which
      are efficiently and rapidly controlled by a specific inhibitor. Endothelium plays
      a pivotal role in these associations. It is a constitutive and inducible source
      of activators and inhibitor. It provides a favorable microenvironment for plasmin
      generation at the vessel surface. Furthermore, the fibrinolytic system
      participating in angiogenesis is implicated in plaque survival. Subjected to a
      pathological environment, endothelial activation leads to change in endothelial
      properties especially by increasing the production of inhibitor of plasminogen
      activators. These modifications could combine to create locally or distantly, a
      state predisposing to thrombosis.

PMID- 9616911
TI  - [Endothelium and hemorrhages].
AB  - Normal endothelium, as well as megakaryocytes, produces and secretes von
      Willebrand factor which plays a pivotal role in haemostasis. It mediates platelet
      adhesion and shear-stress-induced aggregation at the site of vessel wall injury
      and also serves as a carrier protein of factor VIII, an essential cofactor in
      coagulation. The quantitative or qualitative abnormalities of von Willebrand
      factor lead to von Willebrand disease, the most common congenital bleeding
      disorder. Over the past few years major progress in the knowledge of the
      synthesis, structure and functions of von Willebrand factor have led to improve
      the diagnosis and treatment of the different molecular forms of von Willebrand
      disease.

PMID- 9616912
TI  - [Angiogenesis and neoangiogenesis].
AB  - Angiogenesis, the development of new capillary networks from the normal
      vasculature, is a fundamental process during embryogenesis. In adulthood,
      angiogenesis contributes to corpus luteum formation, placental implantation and
      wound healing and is also required in some pathological conditions such as
      several intraocular syndromes, growth of solid tumors, and metastasis. Many
      factors are involved in the regulation of neovascularisation among which FGF-2
      (fibroblast growth factor-2) and VEGF (vascular endothelial growth factor) are
      considered as key inducers. Their biological activity is highly controlled by
      extracellular matrix components and angiostatic factors. Better understanding of
      the molecular mechanisms regulating angiogenesis should contribute to the
      development of new molecules to be used for the treatment of neovascularisation
      linked diseases.

PMID- 9616913
TI  - [Role of the endothelium in leukocyte trafficking].
AB  - Vascular endothelium controls leukocyte recirculation and recruitment, receiving
      messages from underlying tissues and transforming them into informations quickly
      read by the passaging leukocytes. These messages induce adhesive interactions
      between leukocytes and endothelium via adhesion molecules. Multiple receptor
      ligand pairs function in 4 steps: initial tethering and rolling of leukocytes;
      leukocyte triggering by chemotactic factors; arrest and strong adhesion to
      endothelium; and ultimately transendothelial migration (diapedesis).

PMID- 9616914
TI  - [Role of endothelial nitric oxide in the regulation of arterial tone].
AB  - Nitric oxide (NO) is the main agent of communication between the endothelium and
      the smooth muscle, involved in vasodilatation. Its vasodilator action requires
      prior tonic contraction of smooth muscle cells, related to vasoactive agents such
      as catecholamines or angiotensin II-induced centripetal communications and
      pharmaco-mechanical coupling. In physiological conditions, NO is liberated
      following constitutive endothelial NO synthase activity in response to shear
      stress generated by the dynamics of blood on the arterial wall. Endothelial
      dysfunction modifying NO production is implicated in different cardiovascular
      diseases such as hypertension, congestive heart failure and atherosclerosis.

PMID- 9616915
TI  - [Endothelium and infections].
AB  - Endothelial cells control vascular homeostasis by regulating haemostasis,
      inflammatory and immune response, vascular tone or angiogenesis. The endothelium
      is the target of infectious agents capable of altering this equilibrium. Such
      alterations may result from a direct cytopathic effect with disruption of
      endothelial integrity, or from an indirect effect due to unregulated activation
      leading to vascular dysfunction. The endothelium is both the target and the
      effector of human vascular diseases associated with infection such as
      atherosclerosis, vasculitis, neuropaludism or graft rejection. A better
      comprehension of endothelial alterations is these diseases should have biological
      and therapeutic implications.

PMID- 9616916
TI  - [Role of the endothelium in atherosclerosis].
AB  - Endothelial injury has long been considered as a prerequisite for atherosclerotic
      plaque formation. Experimental and clinical studies have proven that during
      lesion development the endothelium is morphologically intact, but its phenotype
      is changed to an activated state, which favours the chronic inflammatory process
      leading to atherosclerotic disease. Endothelium is involved in atherosclerosis in
      several manners including: 1. subendothelial accumulation of atherogenic
      lipoproteins, through the barrier properties of the endothelium; 2. intimal
      accumulation of macrophages, through recruitment and adhesion of monocytes, when
      endothelial cells are activated; 3, vasospasm, when its vasodilatory properties
      are altered; 4, thrombus formation, when the endothelium is eroded.

PMID- 9616917
TI  - [Genital hemorrhage in women after puberty. Diagnostic orientation].

PMID- 9616918
TI  - [Ear discharge, otalgia. Diagnostic orientation].

PMID- 9616919
TI  - [Bimalleolar fracture in adults. Mechanism, diagnosis, treatment].

PMID- 9616920
TI  - [T cells and cellular immunity. Receptor T (structure, diversity, repertory.
      Differentiation antigens (CD4, CD8). Activation. Helper cells T and
      immunoregulation. Lymphokines (interferons, TNF, IL1, IL2, IL4) and cytotoxicity.
      Concept of cell immunity deficiency].

PMID- 9616921
TI  - [Acute lymphoblastic leukemia (adults and children). Diagnosis, course].

PMID- 9616922
TI  - [Congestive heart failure in adults. Etiology, physiopathology, diagnosis,
      course, treatment].

PMID- 9616923
TI  - [Primary and secondary syphilis. Epidemiology, diagnosis, treatment].

PMID- 9616924
TI  - [Experimental vasectomy: comparison of the testicular structure with various
      surgical techniques].
AB  - We have performed experimental vasectomies in dog in order to study different
      repercussions of various surgical techniques on the testicular structure. The
      closed technique, with ligature of both cut ends of the sectioned vas deferens
      caused a severe tubular atrophy, which finally destroyed the architecture of the
      testis with compensating hypertrophy of the intertubular connective tissue. The
      technique of the "open cut end", leaving the proximal end free and allowing the
      normal drainage of the vas deferens into the interstitial space of the spermatic
      cord, had not any influence on the testicular-structure, at least in the studied
      period of time, now one year. We can't reject any long-term immunological
      phenomena. The conclusion of this study is that the peculiarities of the surgical
      techniques of vasectomy have a decisive influence on the preservation of the
      testicular structure.

PMID- 9616925
TI  - [Morphometric correlation at the experimental level of renogram with renal
      arterial stenosis].
AB  - RATIONALE: A reduction of the renal size seen with the nephrogram (intravenous
      urography) has been described in renal artery stenosis. Such reduction, however,
      has not been quantified and the evolution is unknown in terms of duration of
      stenosis evolution. METHODS: Experimental study in rats which underwent
      controlled stenosis of a renal artery, with evaluation, using planimetry of the
      area and perimeter of the nephrogram, of the consequences such stenosis had at
      different observation intervals (30, 90 and 180 days). The effects of the
      stenosis relative to the duration of the experiment is also evaluated. RESULTS:
      The area and perimeter of the nephrogram become reduced in kidneys with artery
      stenosis. Besides, this reduction increases over time. CONCLUSION: The area and
      perimeter of the nephrogram are a useful method to study renal artery stenosis in
      rats.

PMID- 9616926
TI  - [Urologic complications of pancreas-kidney simultaneous transplantation].
AB  - Pancreas Transplantation (PT) is the only available therapy today for diabetes
      that allows an insulin-independent euglycemic state with complete normalization
      of glycosilated haemoglobin levels. Survival of patient, pancreatic graft and
      renal graft is 93%, 86% and 90% respectively at one year and 90%, 84% and 85% at
      three years. The most accepted method for exocrine drainage in most centres where
      simultaneous pancreas-kidney transplantation is being performed is vesical
      drainage. In spite of the improvements achieved in graft and patient survival, it
      is evident that a most frequent use of this type of technique involves a greater
      number of urological complications (repeat infections, haematuria, fistulae or
      leakage, reflux pancreatitis, urethral stenosis and disruption, dehydration and
      acidosis, previous diabetic bladder) and the familiarization of the urologist
      with this type of disease in immunodepressed patients. This paper reviews the
      current situation and illustrates the general approach regimes in our Pancreas
      Kidney Transplantation Unit with regard to each complication.

PMID- 9616927
TI  - [Adrenal gland incidentaloma in the oncologic patient: is its histologic study
      obligatory?].
AB  - OBJECTIVES: To analyze the need for histological study in suprarenal
      incidentalomas in the specific status of the oncological patient. MATERIAL AND
      METHODS: 21 patients with tumoral suprarenal masses, 12 diagnosed in the initial
      study and 9 during the follow-up RESULTS: 16 masses were benign in nature and 5
      were metastatic. Neither the location nor the staging of the initial tumour, the
      time of diagnosis, or the hormonal study were of any use to separate the
      primitive tumour from the metastasis. All metastasis were equal to or greater
      than 5 cm in size. Radiological study only confirmed the nature of the tumour in
      a few cases. Percutaneous biopsy was resolutive in 4/8 cases (50%).
      Suprarenalectomy was performed in 15 occasions, associated in 10 to surgical
      treatment of the primary therapy with not added morbidity. CONCLUSION: When
      incidentaloma is detected in tumoral patients at the time of diagnosis, it
      requires an histological study which in 1 out of 3 cases will modify the
      therapeutic attitude in the presence of metastasis. If the incidentaloma is
      detected during follow-up, it may be monitored in terms of evolution as we would
      only be delaying a palliative treatment.

PMID- 9616928
TI  - [Superficial cancer of the bladder: which controls should follow and for how long
      the free of tumor patients?].
AB  - OBJECTIVES: To answer the following question: what monitoring and for how long
      should be maintained in patients with Ta-T1 vesical neoplasia and no tumoral
      relapse? MATERIAL AND METHOD: Analysis of relapse probabilities in 123 patients
      with Ta-T1G1G2G3 primary tumours who had not relapsed for at least three years of
      follow up after transurethral resection. All patients were treated between
      January 1976 and December 1986; they all have follow-up potential of over 10
      years. Mean follow-up 8.1 years, minimum 4 years, maximum 18 years. RESULTS:
      Probabilities of relapse at 3 to 5 years, 6 to 10 years, 11 to 18 years are 18%%,
      24% and 13%, respectively. Relapses were superficial in 38 cases (90%),
      infiltrant in 4 (10%) G1 in 21 (50%), G2 in 12 (29%), G3 in 9 (9%), single in 33
      (79%), multiple in 9 (21%), under 2 cm in 35 (83%), over 2 cm in 7 (17%).
      CONCLUSIONS: Epidemiologically, individuals with a background of surface vesical
      tumour have a much higher risk of relapse than the Spanish normal population and
      therefore they should be monitored for life. Relapses are usually superficial,
      low grade, single and small in size. Cystoscopy is the monitoring technique
      offering more possibilities for detection.

PMID- 9616929
TI  - [Rate of external consultation utilization. Organizational and managerial basis
      of a urology service].
AB  - INTRODUCTION: The frequency of visits to an outpatients office is indicative of
      the proportion of population to be served at that location. MATERIAL AND METHOD:
      Analysis of the frequency of new cases to an outpatients office over one year and
      correlation with the conditions treated over the corresponding period.
      OBJECTIVES: To know the overall frequency of new cases, by condition, affected
      organ and group of diseases. To know the percentage of surgical resolution of
      those conditions. To infer from these data the resources necessary in terms of
      offices, operating theatres and staff RESULTS: The outpatients office shows an
      overall frequency of new cases of 124/10000 people/year. The highest frequencies
      by condition, affected organ and group of diseases correspond to BPH,
      inguinoscrotal area and andrology. 35% of all new cases are managed surgically.
      17.5% BPHs and 16.4% prostate carcinomas undergo surgery. The necessary resource
      are inferred to be: 1.5 ambulatory operating theatres/week, 2-2.5 central
      operating theatres/week. 5-6 office visits/week and 3 urologists. CONCLUSIONS:
      The study on the frequency of visits to the outpatients office is a useful tool
      for the organization and management of the Urology Service.

PMID- 9616930
TI  - [Evaluation of urology training of resident internal physicians of the Valencian
      community. Quality control].
AB  - Report on the results of a survey conducted among Urology residents in the
      Valencian Community. Evaluation of the training level of the MIR system, both
      overall and by areas. Presentation of the views obtained with regard to possible
      modifications to raise their training level and improve their professional
      future.

PMID- 9616931
TI  - [Primary signet cell adenocarcinoma of the bladder].
AB  - The primary signet-ring cell adenocarcinoma of the bladder is a rare tumor, with
      great biological aggressivity and bad prognosis. We report a clinical case of a
      65 years old patient, starting with bladder irritative symptoms and suffering
      from advanced disease at the initial diagnosis. We review clinical and
      etiopathogenic aspects about this entity.

PMID- 9616932
TI  - [Ureteral metastasis of renal parenchyma tumor].
AB  - Metastatic involvement of the ureter due to renal parenchyma neoplasia has been
      reported in a total of 53 cases in the literature, the described mechanisms for
      tumoral spread being: haematogenic, lymphatic, canalicular and direct. Time to
      appearance of metastasis is far from prompting agreement among the authors in
      terms of its synchronous or metachronous nature. The most frequently reported
      symptoms are total and painless haematuria, and obstructive uropathy: CAT,
      percutaneous nephrostomy (for locally advanced disease) and endoscopy, are the
      most frequently used diagnostic tools. The only available therapy is
      nephrouretectomy for a diagnosis synchronous with the primitive tumour, and
      uretectomy for metachronous emergence. This paper reports on a case of
      sarcomatoid renal tumour with ipsilateral synchronous involvement of the ureter,
      which caused an obstructive uropathy treated by nephrouretectomy.

PMID- 9616933
TI  - [Spermatic cord lipoma].
AB  - In spite of being the most frequent tumour in this location, together with
      adenomatoid tumours, the spermatic cord lipoma is a very rare entity (30-35%
      each). The etiology is unknown but linked to a constitutional factors, obesity,
      an its presentation is more frequent in the fifth or sixth decade of life. It
      progresses always as an asymptomatic tumour, usually unilateral, showing a swift
      growth to masses larger than 10 cm. Diagnosis is reached by ultrasound and CAT
      when doubtful, and the histology is confirmed during scrotomy. Tumour resection
      is the choice treatment. In the case reported here there had been two earlier
      resections, so relapses and pseudo-relapses should be taken into account.
      Although rare, a few cases of lipoma degeneration to liposarcoma have been
      reported.

PMID- 9616934
TI  - [Retroperitoneal ganglioneuroma].
AB  - Presentation of one case of retroperitoneal ganglioneuroma in a 31-year old
      female. This type of neoformation, with origin at the sympathetic system nodes
      level, is considered to be the benign homologous of neuroblastoma. Peak incidence
      age ranges from 3 to 20 years. The retroperineum is one of the most frequent
      sites, second only to the mediastinum. Diagnosis is normally casual and is
      considered definite when, following mass removal and completion of the
      pathoanatomical study, the presence of neuroblasts in the tumour can be ruled
      out.

PMID- 9616935
TI  - [White atrophic vasculitis. Infrequent genital lesion. Review of a case].
AB  - Case report of a 54-year old patient, calling on the emergency unit with
      testicular pain and necrotic-looking lesions in the skin and the scrotum. After
      ruling out a Fournier's gangrene, the diagnosis was reached by scrotal biopsy,
      the pathoanatomic report confirming the presence of an infrequent vascular
      disease, segmentary hyalinizing vasculitis, on which we make a review of the
      literature.

PMID- 9616936
TI  - [Urethral diverticulum complicated with giant lithiasis].
AB  - Presentation of one case report of acquired urethral diverticulum in a male with
      giant urethral lithiasis. Urethral diverticulum are rare entities in males, the
      condition being more frequent in females. In general, they are acquired in up to
      90% cases, the remaining 10% being hereditary Giant urethral lithiasis is also
      uncommon in our milieu, incidence being higher in Eastern Countries; 4-10% of
      urethral diverticulum are occupied by lithiasis. Diagnosis is mainly through
      clinical symptomatology involving the development of a perineal mass or phlegmon;
      however definite diagnosis is made through CUMS. Management of giant diverticulum
      in males is by open surgery, preferably a one-step diverticulectomy procedure; in
      cases such as the reported here, where urethral stenosis or a significant
      inflammatory involvement of the periurethral tissues is present, a two-step
      urethroplasty should be preferred.

PMID- 9616937
TI  - [Retroperitoneal cystic mesothelioma and lymphangioma].
AB  - Retroperitoneal cysts are uncommon entities of difficult diagnosis because of
      their insidious symptomatology. Urinary apparatus involvement is quite often the
      mode of presentation and the reason for calling on the urologist. The origin of
      many of these retroperitoneal cysts remains practically unknown. Surgery with
      exeresis is the choice management method. Follow-up is necessary for cystic
      mesothelioma because of the highly frequent relapses. The outlook of hormonal
      conservative therapy for relapses appears as a future alternative to treatment.

PMID- 9616938
TI  - [Pyourachal cyst. A diagnosis to keep in mind].
AB  - Urachal conditions are relatively exceptional, cystic formations being the most
      commonly reported. Urachal cysts remain silent and are not diagnosed except for
      the presence of associated complications such as: infection, lithiasis, re
      permeabilization and malignant degeneration. This paper presents one patient with
      an infected urachal cyst (pyourachal) which required surgical exeresis. A
      literature revision is made of the clinical, diagnostic and therapeutic aspects.
      Emphasis is made on the relevance of a high index of suspicion considering its
      small incidence, the absence of specific clinical sings and the possibility of
      mimicking different abdominal pictures. Also the usefulness of ultrasound and
      computerized axial tomography in the diagnosis, and the need for surgical
      exeresis, including a vesical cup rim, are emphasised.

PMID- 9616939
TI  - [Testicular epidermoid cysts. Report of 2 cases].
AB  - Testicular epidermoid cysts are benign tumours which account for less than 1% of
      all testicular tumours. Their uncertain histogenesis, difficult pre-operative
      diagnosis and controversial therapeutic approach are at the base of this paper.
      Report on two patients, 20- and 21-year old, with testicular epidermoid cysts
      treated by inguinal radical orchiectomy and tumorectomy, respectively. Literature
      review focused on the diagnostic and therapeutic aspects. Emphasis on the
      relevance of ultrasound for pre-operative diagnosis. We also advocate for a
      conservative management if their presence is suspected or in the presence of
      negative tumoral markers.

PMID- 9616940
TI  - [Postbiopsy giant pseudoaneurysm in renal transplant: treatment with
      embolization].
AB  - Pseudoaneurism in renal grafts is a well known complication of the percutaneous
      biopsy. Colour Doppler has been shown to be the choice technique for their
      diagnosis and subsequent control, the most effective treatment being
      embolization. This paper presents an unusual form of pseudoaneurism in terms of
      its size (up to 8 cm diameter) in a renal graft, following performance of a
      percutaneous biopsy with automatic needle. The findings of the colour Doppler
      study and the angiography are shown and discussed, as well as the treatment by
      embolization with metal spirals which achieved the stable, complete occlusion of
      the lesion after six months control.

PMID- 9616941
TI  - [Neuroprotective action of aspirin].

PMID- 9616942
TI  - [Indications for aspirin on the centennial of its discovery].

PMID- 9616943
TI  - [Aspirin and surgery].

PMID- 9616944
TI  - [Biotinidase deficiency].

PMID- 9616945
TI  - [Surgery of stomach ulcer in Spain. Surgical ways that led to the cure of stomach
      and duodenal ulcer in Spain].

PMID- 9616946
TI  - [History of the Museum of Forensic Anthropology, Paleopathology and Criminology
      of the School of Legal Medicine of the Complutense University].

PMID- 9616947
TI  - [Immunosuppressive agents: side effects].

PMID- 9616948
TI  - [Multivariate study of hospital infection and mortality of critical patients with
      burns].

PMID- 9616949
TI  - [Contacts, network systems, synapses].

PMID- 9616950
TI  - [Tridimensional analysis of idiopathic scoliosis].

PMID- 9616951
TI  - [Osteointegrated implants: a third dentition. Myth or reality].

PMID- 9616952
TI  - [Innervation of the auditory receptor and cochlear nuclei].

PMID- 9616953
TI  - [Transplant of the mitral valve].

PMID- 9616954
TI  - Research in bioethics: a bridge between science and philosophy.
AB  - The author makes an inquiry into the diverse attitudes that the culture of
      Western man has assumed towards the concepts of truth and morality. Analysing
      five different attitudes in the consideration of relationships between "good" and
      "truth", he concludes that a concrete definition of truth and morality can only
      be sought after but never reached. Similarly, a concrete definition for bioethics
      can only be attempted, more questions than answers arise. Bioethics needs to
      define its principles to achieve its foundation. Yet bioethics, being a bridge
      between science and philosophy, has not succeeded in finding unequivocal
      principles, but it has only succeeded in posing questions. Bioethics is thus a
      despairing but also unavoidable venture.

PMID- 9616955
TI  - Brain research and human diversities.
AB  - Brain research, and neuroscience in general, seems to meet cultural needs rather
      than therapeutic necessities. There is no evidence indeed that recent findings-
      even if they are important--will have therapeutic application in the short run.
      Although indirect and direct costs of neurological and psychiatric diseases are
      outrageous, clinical research in these fields is not at all encouraged. Research
      in neuroscience seems above all interested in challenging some cultural paradigm.
      Likewise another great and similar venture, the Human Genome (HUGO) Project, also
      brain research seems to be a scientific enterprise which primarily aims at
      grounding human diversities on biological diversities. Yet can biology ever
      substitute the multiculturalist dream?

PMID- 9616956
TI  - Brain fantasies.
AB  - Any reasoning concerning the brain must face two different objects: the organ
      brain, and the metaphoric-brain. Because we know so little about the true nature
      of brain/mind relations, we have to be extremely careful and humble when coping
      with brain and mind. It is necessary above all to make a clear distinction
      between reality and fantasies, between organ-brain and metaphoric-brain.

PMID- 9616957
TI  - Ethical aspects to be considered in brain banking.
AB  - A brain bank is a prospective source of adequately collected and preserved
      tissues of the central nervous system obtained via a donor program, which are
      supplied for neurobiological research. Brain tissue banks collect brains, serum
      and cerebro-spinal fluid from patients suffering from neurological disorders such
      as Alzheimer's diseases, Parkinson's disease and multiple sclerosis for
      diagnostic purposes and for the development of future diagnostic tests. To create
      and develop the right infrastructure underlying brain bank activities, one should
      have a medico-legal and ethical support according to local legislation. From an
      ethical point of view, brain bank activities can be divided into the following
      categories: a) factors related to the donor program; b) factors related to
      handling and management of organs; c) factors related to scientific research. The
      present paper deals with the above mentioned issues according to world-wide
      recognised ethical considerations and recommendations of several official
      statements, and specifies the objectives of the European Brain Bank Network
      (EBBN).

PMID- 9616958
TI  - Advances in brain imaging: a new ethical challenge.
AB  - Technical advances in the past 25 years permitted substantial advances in the
      neuroimaging field, expanding the diagnostic and research potentials and
      significantly reducing the use of old invasive imaging techniques for research
      purposes. The safer procedures now available allow acquisition of reference data,
      morphological assessment and functional characterisation from healthy volunteers.
      However, enrollment of volunteers is still a sensitive ethical issue. Ethical
      problems related to informed consent, for both research and diagnostic
      procedures, in patients with neuropsychiatric disorders represent an additional
      crucial issue. Furthermore, with both functional and structural neuroimaging
      studies, there is a theoretical risk of violation of individual privacy. Research
      in the neuroimaging field should tend to increase the amount of information
      obtained through appropriate post-processing procedures, including multimodality
      image fusion, and to limit stress and discomfort.

PMID- 9616959
TI  - Ethical aspects of research on brain morphology in psychiatric patients.
AB  - Morphometric and functional brain research is now an integral part of the most
      concentrated effort in a century to understand some of the most distressing
      illnesses to which man can fall victim. It will undoubtedly expand. The only ones
      with anything to fear from this work are those who, for ideological reasons,
      cannot accept its basic premises. The ethical issues it raises are not in general
      insurmountable, though the questions posed by the concept of informed consent
      remain.

PMID- 9616960
TI  - Informed consent and psychiatric research.
AB  - The general problem with research is that its purpose does not necessarily
      benefit an individual patient now. In psychiatry the specific problem is that
      psychiatric patients may have a reduced mental competence, because of their
      illness. Thus the specific clinical problems of the research subjects may impede
      the ethical requirements of the research. To try to solve this conundrum, we may
      need to move away from a vision of psychiatric ethics which is rights and
      individual based, and find another, which understand that ethical decision are
      made in the context of relationship: psychiatrist-patient, patient-society,
      analyst-patient, psychiatrist-society.

PMID- 9616961
TI  - Diagnosis of schizophrenia: future ethics.
AB  - The healthcare burden, to the affected individual, their family and to society,
      caused by the schizophrenias provides a strong moral appeal for non
      discriminatory allocation of resources for both research and service provision.
      Nevertheless, the anticipated advances in clinical research findings are likely
      to lead to a new healthcare situation where a number of values and moral appeals
      are likely to be in conflict. The sources of these conflicts are explored with
      respect to the nature and origin of the schizophrenias, the challenges of pre
      clinical and possible prenatal diagnosis. It is argued that the ethical problems
      associated with discovery of early markers for the development of schizophrenia
      should be anticipated and appropriate guidelines developed in advance of their
      realisation. Experience of other screening programmes strongly cautions against
      the introduction of such markers before the benefits and safety aspects have been
      clearly defined.

PMID- 9616962
TI  - [The Chernobyl incident: dose assessment in Italy and Europe].
AB  - The radiological impact of Chernobyl accident on the Italian population has been
      reassessed on the basis of the activity average values, measured in environmental
      and food matrices since 1986. The evaluation has been made taking into account
      the new risk estimates by the International Commission on Radiological Protection
      (ICRP). Moreover, in order to compare the calculated doses with data from Whole
      Body Counter and to check models describing the time trend of radioactive
      contamination, the activity levels systematically measured in the Emilia Romagna
      district (Northern Italy) were considered. The dose assessment has been compared
      with the European one made by UNSCEAR (United Nations Scientific Committee on the
      Effects of Atomic Radiation).

PMID- 9616963
TI  - [The Chernobyl incident: emergency management in Italy and other European
      countries].
AB  - Several measures were adopted by European countries in the aftermath of the
      Chernobyl accident. In this paper these measures are reviewed and the European
      Communities initiatives for food marketing and exports are analyzed, together
      with the reference levels for radioactive concentration in the main food matrices
      chosen in different European countries in the very few days after the accident. A
      particular attention has been devoted to the emergency management in Italy,
      outlining exhaustively the laws enforced at the time of the accident and
      explaining how the reference levels for food contamination were chosen. Finally,
      a tentative balance about emergency management in Italy is struck and some
      questions are raised about the commitments undertaken or to be undertaken by
      international institutions.

PMID- 9616964
TI  - [Complex biological systems as experimental and prenatal toxicology models].
AB  - Experimental biomedical sciences have emphasised the use of model systems in the
      study and understanding of physiological and pathological processes.
      Developmental biology, genetics and prenatal toxicology, dealing with cellular
      differentiation, organogenesis and dismorphogenic alterations, have shown that
      system models, even those far removed from mammals and humans in the zoological
      scale (e.g. C. elegans, Hydra, Drosophila), can be useful tools for understanding
      pathogen mechanisms in developmental toxicology. In particular the study of
      neural tube and its alterations shows how a biologically complex model (such as
      the laboratory rodent) necessitates, in turn, a series of models to thoroughly
      analyse and clarify the limits and levels of research.

PMID- 9616965
TI  - [Modulation of inflammatory cells in helminth infections].
AB  - In this review, different mechanisms by which helminthic parasites modulate the
      activities of inflammatory cells are considered. Examples are presented of
      parasitic products interfering with lymphocytes and their products such as
      antibodies, then modifying both regulation and effector response of the immune
      system. Furthermore, examples of interference on the complement system are
      illustrated. Parasites such as Ancylostoma caninum produce factors such as the
      neutrophil inhibitory factor (NIF) capable of inhibiting the neutrophil
      endothelium adhesion, whereas Trichinella spiralis produces a glycoprotein, the
      45gp, which inhibits different neutrophil functions. Parasites are also able to
      modulate the function of the monocytes-macrophages which in some infections play
      a crucial role; the modulation of NO synthesis is also relevant to the host
      parasite relationship. Finally, the different anti-oxidant systems of helminthic
      parasites are described. The comprehension of such evasion mechanisms of the
      immune response is necessary to develop vaccines and new drugs, but it is also
      useful to clarify the contribution of parasites to immune system evolution.

PMID- 9616966
TI  - [Human pathology caused by free-living amoebae].
AB  - Naegleria fowleri, Acanthamoeba spp. and Balamuthia mandrillaris are free-living
      amoebae that occasionally may induce pathology in human beings. CNS disease due
      to N. fowleri, called "primary" amoebic meningoencephalitis, is acquired after
      exposure to polluted waters in swimming pools, rivers, and lakes. The clinical
      course is acute, often fulminant and characterized pathologically by necrotizing
      hemorrhagic meningoencephalitis, involving mainly the base of the brain,
      brainstem and cerebellum. In contrast, some Acanthamoeba spp. and B. mandrillaris
      cause opportunistic, chronic "granulomatous" encephalitis in subjects
      pathologically or iatrogenically immunocompromised. There are, most likely, foci
      of protozoa in lung and skin reaching the CNS by hematogenous route. Only
      Acanthamoeba spp. can also produce severe, subacute keratitis, mainly today in
      contact lens wearers.

PMID- 9616968
TI  - Clinical and pathological prognostic factors in canine mammary tumors.
AB  - In the present study, clinical and reproductive variables and pathological
      features were evaluated as prognostic factors in canine mammary tumor disease.
      Seventy-four female dogs free of distant metastases at diagnosis were followed-up
      during a period of 18 months after the surgical excision of mammary nodules. Age
      at presentation, tumor size, lymph node involvement, histological malignant grade
      and nuclear grade were proven to act as variables able to predict the overall
      survival time in dogs with mammary neoplasms. Disease free survival time was
      associated to the age, the presence of multiple malignant tumors, tumor size and
      ulceration of the skin.

PMID- 9616967
TI  - Hookworm infection and disease: advances for control.
AB  - Advances in epidemiology and in control strategies of hookworm infection and
      associated disease were reviewed. Recent estimates indicate that hookworms infect
      approximately 1.3 billion people worldwide, and 96 million suffer from associated
      morbidity, including also insidious effects on nutritional status and on physical
      and intellectual development. Recent research studies on iron loss and iron
      deficiency anaemia associated to hookworm infection were irondeficiency anemia
      associated to hookworm infection were reviewed. Recommendations for planning
      strategies for the control of hookworm infection were addressed and epidemiology,
      targets, chemotherapy, health education, sanitation, monitoring and evaluation in
      helminth control programmes were discussed. Special relevance was given to
      chemotherapy with new, single dose broad spectrum, safe anthelminthic drugs as
      the mainstay of control strategy to reduce intensity of infection, iron
      deficiency anaemia and other morbidity indicators associated with hookworm
      infections. For the control of transmission of hookworm infection, periodic
      chemotherapy should be implemented in the context of ongoing improvement of
      sanitation and promotion of health education. These elements should be integrated
      into the prevailing system of primary health care and must be based on
      multisectoral collaboration to ensure sustainability of control programmes.

PMID- 9616969
TI  - [Veterinary environmental epidemiology: the case of respiratory pathology in the
      dog].
AB  - The correlation between environmental pollution and human health is one of the
      most important topics in public health. Environmentally-induced diseases
      generally show multifactorial etiology and their occurrence is dose-related; they
      can be included among the emergent diseases also in veterinary medicine. The
      epidemiological study of naturally occurring environmental diseases in animals,
      regarded as sentinel health events, can provide valuable information on agents
      being studied in human environmental epidemiological research. The epidemiologic
      aspects of naturally occurring diseases of domestic animals have so far received
      inadequate attention. Surveys have usually consisted of descriptive pathologic
      reports or of simple listings of case. There has been little or no attempt to
      relate the number of cases to the underlying population, thus there is little
      information on the prevalence rates of various animal diseases compiled according
      to age, breed, sex or environment. This paper reviews epidemiological studies of
      pet animals with spontaneously occurring respiratory diseases and attempts to
      determine the value of the animal in general and the dog in particular as a
      comparative model for environmental health.

PMID- 9616970
TI  - [Health and hygiene aspects of the production of high-quality compost].
AB  - The present national and international trends about waste management favour
      recycling and recovery of waste either as materials or as energy. Therefore, it
      can be supposed that recycling activities of materials as for example the
      composting of urban waste organic fraction will be more and more encouraged in
      the future. Nevertheless, if we intend really to develop a market of recycling
      and recovery of waste, the quality of products obtained must be especially
      considered. As regards the compost, these problems have taken a great importance
      in the last years, since only high quality compost finds utilization in
      agriculture. In this paper, we investigate the procedure to carry out in order to
      obtain a compost of high quality either from a chemical, microbiological or
      technological point of view, by examining particularly the effects on compost
      quality, in consequence of separation of some specific waste streams at source.

PMID- 9616971
TI  - [Insecure attachment and psychosomatic skin disease].
AB  - Alexithymia is not infrequent among psychosomatic patients. The incapacity to
      decode one's own emotional experience implies an exacerbation of the
      physiological response through a recursive loop. If this vicious circle is
      maintained it can increase the risk of psychosomatic diseases which could be in
      this way regarded as functions of external meaningful events mediated by the
      central nervous system. The meaning varies from one individual to another and
      depends on his cognitive-emotional organisation. In order to study such an
      organisation, it can be useful to classify his mental state regarding his
      attachment. The authors, who previously observed an association between
      psychosomatic skin disease and the "non-free" mental state with regard to
      attachment, suggest that further studies on psychosomatic patients should be
      conducted applying the principles and methods of the attachment theory.

PMID- 9616972
TI  - The Jakarta Declaration on Leading Health Promotion into the 21st Century.

PMID- 9616973
TI  - Prostitutes and AIDS prevention: a survey of Italian sexually experienced young
      men.

PMID- 9616974
TI  - [Vaccination rate for triple measles-rubella-mumps vaccine in Empoli Val d'Elsa
      area health district U.S.L. 11, Tuscany Region].

PMID- 9616975
TI  - [Humoral and cellular immunity in response to BCG vaccination. A study of a
      sample of students of the Campania region].

PMID- 9616976
TI  - [Reliability of data of hospital discharge and anatomo-pathological records for
      population cancer registration].

PMID- 9616977
TI  - [Evaluation of microbiological parameters of mineral waters bottled in Italy].

PMID- 9616978
TI  - [Decontamination of asbestos-containing objects].

PMID- 9616979
TI  - [Endoscopic therapy of ureterocele: description of a case].
AB  - Ureterocele is a cystic dilatation of the terminal intravesical ureter; the
      therapeutic options are different and correlated on upper and lower urinary tract
      anatomy. The goals of treatment include control of infection, protection of
      ipsilateral and controlateral renal units and maintenance of vesicoureteral
      continence. The endoscopic approach is still debated; many authors report a
      higher risk of post-operative vesticoureteral reflux and further surgery. When
      the intravescical ureterocele is associated with the upper pole of a duplex
      system a small endoscopic transverse incision as definitive treatment has gained
      support in more than 90% of cases. We report a case of intravesical ureterocele
      with a complete duplex system, in a young woman treated by endoscopic incision as
      "smiling mouth" with good results of 6 months follow-up.

PMID- 9616980
TI  - Assessment of glomerular filtration rate by means of the four-, and more
      compartmental closed models after a single intravenous injection.
AB  - This is the continuation of our study on the estimation of glomerular filtration
      rate (GFR) after a single intravenous injection using the closed compartmental
      model. In our previous study, a three-compartment closed model including blood,
      periphery and urine was developed to estimate GFR. Although the model developed
      in our previous study is an improvement of the two-compartment open model
      currently used in the assessment of GFR, there is a limitation in our previous
      model and the current two-compartment open model, i.e. these models are suitable
      for the tracers whose elimination is solely via the renal pathway. However,
      several tracers used to assess GFR are eliminated via both renal and non-renal
      pathways, therefore it is also important to develop the models to include the non
      renal elimination pathways for these tracers. In the present study, all the
      possible non-renal elimination pathways were modelled by means of four-, five-,
      and n-compartment closed models after a single intravenous injection. Although
      more compartments were included into the modelling, the results show that the
      inclusion of more non-renal elimination compartments only leads to the increase
      in the similar analytical solutions for these compartments. Therefore, the
      equation in our previous study can be used to estimate GFR for the tracers whose
      elimination is not only via the renal pathway, but also via the non-renal
      pathway, even via an arbitrary number of the non-renal pathways.

PMID- 9616981
TI  - [Percutaneous, laparoscopic, and surgical treatment of idiopathic varicocele:
      analysis of costs].
AB  - Idiopathic varicocele can compromise the spermatogenetic function of the testicle
      and associate with alterations of the semen quality. The treatment of varicocele
      stops the progress of testicular damage and improves spermatogenesis and semen
      parameters. These are the main alternatives to the traditional surgical treatment
      of varicocele retrograde percutaneous occlusion of the internal spermatic vein
      using sclerosing agents and embolizing devices (either separately or in
      combination), microsurgical ligation via inguinal or sub-inguinal approach,
      laparoscopic ligation and, more recently, antegrade scrotal sclerotherapy. None
      of these techniques can be considered the "gold standard" therapy. Literature
      does not point out any significant difference between them, either considering
      the absence of reflux percentage, or the improvement of semen quality, or the
      pregnance rate. Therefore cost comparison may be a valid criterion in the choice
      of treatment for varicocele correction. The total cost of the surgical
      retroperitoneal unilateral ligation of the internal spermatic vein is 968,805
      Lire, while for the bilateral ligation it is 1,118,285 Lire. The costs of
      sclerotherapy and percutaneous embolization are respectively of 698,750 Lire and
      1,708,950 Lire. The combination of the two techniques amounts to 1,918,230 Lire.
      Laparoscopic bilateral ligation costs 2,437,935 Lire. Antegrade scrotal
      sclerotherapy costs 191,035 Lire if unilateral, 216,580 Lire if bilateral. After
      considering these data we can say that antegrade scrotal sclerotherapy is the
      first choice economically in the treatment of both unilateral and bilateral
      varicocele.

PMID- 9616982
TI  - [Clinical efficacy of intravesical BCG treatment for superficial bladder
      neoplasms with respect to the iduced immune response].
AB  - We evaluated the immune response after BCG treatment in superficial bladder
      cancer analyzing the modifications induced on lymphocytic sub-populations. In 21
      patients with superficial bladder cancer we performed TURB and after 12 days
      began the induction cycle of 6 weeks with Pasteur BCG (75 mg/50 micromilligrams),
      followed by one instillation monthly for one year. Before treatment every
      patients underwent Mantoux intradermoreaction, blood-count and determination of
      peripheral blood lymphocytic subpopulations. Blood-count and lymphocytic
      subpopulations were repeated after 1 week, after 6 weeks, after 3 months and
      after 1 year. During cystoscopy after 3 months every patients underwent vesical
      biopsy. CD4+ and CD8+ are mainly interested among lymphocytic subpopulations at
      the beginning: BCG decreased CD4+ value in the patients with complete response
      and then it increased CD4+ and reversed the ratio between CD4+ and CD8+ on
      vesical mucosa.

PMID- 9616983
TI  - [Correlation between the leak point pressure and the clinical grade of
      incontinence].
AB  - We evaluated one-hundred and forty-six women with stress urinary incontinence
      (SUI), mean age 61.5 years, with clinical examination, urodynamics and patient
      history, grading the subjective degree of SUI according to SEAPI QMM
      classification. SUI was grade 1 in 73 pts (mean LPP 107, 7 cmH2O, mean maximal
      urethral closure pressure 59, 13 cmH2O), grade 2 in 36 (mLPP 55, 4 cmH2O, mMUCP
      50, 3 cmH2O), grade 3 in 37 (mLPP 32, 29 cmH2O, mMUCP 33, 76 cmH2O). There is
      statistically significant difference in mLPP (p = 0.001) and mMUCP (p = 0.02)
      among three groups. The grade of SUI increases as the likelihood that LPP will be
      < or = 90 cmH2O or < or = 60 cmH2O (72.2% of pts with grade 2 has a LPP < or = 60
      cmH2O, 100% of pts with grade 3 has a LPP < or = 60 cmH2O). Women with severe
      leakage and/or predisposing factor (PF) to intrinsic sphincter deficiency are
      likely to have a low LPP: all patients with SUI grade 3 and PF have a LPP < or =
      60 cmH2O, 77% of pts with SUI grade 3 or PF has a LPP < or = 60 cmH2O. Women with
      higher grades of leakage and PF are significantly more likely to have a very low
      LPP and intrinsic sphincter deficiency.

PMID- 9616984
TI  - Some remarks on the epidemiology of acute urinary retention.
AB  - Acute urinary retention is an unpleasant, painful experience which requires
      immediate medical, and frequently surgical intervention. Population studies
      reveal that acute urinary retention is a common event: a 60 year-old man who
      survives a further 20 years has a 23 per cent probability of experiencing an
      acute episode of urinary retention. About half of acute retention episodes appear
      to be linked to general anaesthesia and a further large population due to the
      natural history of benign prostatic hyperplasia. The risk of acute urinary
      retention increases with increasing age. There are a number of other risk factors
      with risk increased in men with moderate and severe urinary symptoms, low peak
      urinary flow rates (less than 12 ml/sec) and among men with large prostates.
      Recent placebo-controlled randomised trials reveal that finasteride is associated
      with a 57 per cent reduction in the hazard ratio of acute urinary retention when
      used for at least two years. Since finasteride acts in a positive manner on the
      major risk factors (finasteride use increases peak urinary flow rate, reduces
      symptom scores in moderately symptomatic men and reduces prostate volume), this
      result is not too surprising. It remains to be determined what the risk factors
      for anaesthesia-induced acute retention are and how they can be altered.
      Nevertheless, the improvement of our knowledge of the epidemiology of acute
      urinary retention in the past 12 months is impressive.

PMID- 9616985
TI  - [Epidemiology of male infertility].
AB  - OBJECTIVE: The aim of the present study has been to analyze the variation of the
      main parameters which define sperm quality in a group of men who were referred to
      our center of sterility during the last ten years of activity. MATERIAL AND
      METHODS: Over the last ten years, we have examined 3203 men ranging from 25 to 50
      years of age. We have considered different parameters of evaluation, such as
      semen volume, motility, total motility count and morphology of spermatozoa; the
      same parameters have been considered for a group of 192 men accustomed to
      consuming coffee, alcohol and tobacco. RESULTS: We have observed no significative
      variations with respect to sperm volume; in spite of this result, we have
      registered a considerable reduction of the frequency of men with normal sperm
      quality, when we have considered parameter such as sperm motility. The evaluation
      of the total motility count has confirmed a progressive reduction during the
      considered period of time. This parameter has also shown the existence of a
      circannual rhythm for the production of spermatozoa, which results minimum during
      the winter and during the warmest months, while it improves during spring and
      autumn. During the considered period, the study of morphology has shown a
      progressive reduction of men with normal semen quality. CONCLUSION: The results
      of our epidemiologic study, conducted over a group of men who have been referred
      to our center of sterility during the last ten years, confirm that the group
      representative of Northern Italy has faced a decline of sperm quality.

PMID- 9616986
TI  - [Seminal fluid today].
AB  - Semen analysis is still today a fundamental stage in male fertility diagnosis. In
      fact it's essential to evaluate didimal functional state and particularly the
      sperm genesis. But a semen analysis with normal parameters does not assure male
      fertility. Except the cases of azoospermia it does not distinguishes fertile from
      infertile patients, but when the sperm quality decrease, the pregnancy rate also
      decrease but rarely touch zero. Reliability of the analysis depends on the
      experience and on the analyst's ability who has to give an opinion about
      fundamental parameters like motility and sperm morphology. It is most correct to
      talk about semen analysis instead of semen examination because is possible to
      obtain not only number and quality of spermatozoa but also hormonal,
      immunological, bacteriological, cytogenetic, biomolecular data. Furthermore in
      the last ten years a lot of functional tests have been perfected, able to value
      accurately the integrity of some spermatozoa's "functional compartments" like
      membrane, acrosoma, DNA, nuclear proteins but these examinations have been
      considered at level assessment only for select cases. Semen analysis remains
      therefore a fundamental examinations in the study of male infertility even if
      rarely it is able to express definitive trials about infertility. In fact this
      always represents a couple problem, particularly of the couple in study.

PMID- 9616987
TI  - [Varicocele and its repercussion on infertility. Indications and limitations of
      surgical intervention].
AB  - According to different Authors, varicocele incidence in unselected population
      fluctuates from 8 to 22% but in selected population affected by sterility
      incidence ranges from 21 to 39%. However other Authors have demonstrated that
      about 50% of patients suffering from varicocele have semen alterations. Various
      mechanisms have been suggested for testicular dysfunction associated with
      varicocele: intrascrotal hyperthermia, reflux of renal and adrenal metabolites
      from the renal vein and hypoxia. The most important semen alterations are
      observed in patients suffering from grade 2 and 3 varicocele and especially these
      patients must undergo surgical operation. According to recent findings, better
      results about the improvement of semen quality are obtained by operating children
      in puberal age. This clinical approach allows a prevention of testicular
      hypotrophy or, when this is already present, its reversibility. Varicocele
      surgical treatment makes use of traditional techniques microsurgical or not and
      mininvasive techniques. After renouncing of intrascrotal varicocelectomy,
      traditional techniques provide ligature and section of ectasic spermatic veins,
      after a surgical high (at level of the internal inguinal ring) or low (over
      inguinal canal) skin incision. Microsurgery allows recognition and protection of
      lymphatic and arterial vessels and execution of microsurgical anastomosis between
      venous spermatic and ileo-femoral circle vessels, when this is necessary.
      Internal spermatic vessels and vas deferens can be visualized through the
      laparoscope and so laparoscopic varicocele treatment was suggested. These new
      techniques and traditional operation are burdened with the same percentage of
      relapses but in laparoscopic procedure complications are more important. Recently
      radiographic occlusion techniques are also utilized (internal spermatic vein
      retrograde scleroembolization); the percentage of relapses is between 4 and 11%,
      with no risk of postvaricocelectomy hydrocele but with risk of loss of kidney
      (migration of the ballon or coil into the renal vein). Surgical treatment of
      varicocele produces a significant improvement in semen analysis in 60 to 80 per
      cent of patients affected by testicular dysfunction. Pregnancy rates after
      varicocelectomy are including from 20 to 60 per cent with most series averaging
      about 35 per cent.

PMID- 9616988
TI  - [The consultation with the candidate couple for intracytoplasmic sperm injection
      (ICSI) using microsurgical epididymal sperm aspiration (MESA) or testicular sperm
      aspiration (TESA). The experience of the MATRIS (Medici Associati per la Terapia
      e la Ricerca dell'Infertilita e Sterilita) center of Milan].
AB  - The authors examine the relationship between doctor and patient during the
      consultation for the therapeutic decision for those couples who have to undergo a
      medical procreation, especially the ICSI by MESA and TESA. The couple's psycho
      emotional involvement and the medical terminology hinder the real possibility of
      communication between doctor and patient. The data relating to a study of 80
      couples done by the authors are presented. They show the need to improve the
      quality of communication between doctor and patient during the consultation. For
      this purpose, on the basis of the research conducted, modification of the
      language used and the support of audio-visual media are suggested during the
      consultation in order to reduce the percentage of the couple's doubts and
      uncertainties.

PMID- 9616989
TI  - [Analysis of a microdeletion in the AZF gene region in azoospermic patients: from
      research to molecular biology laboratory routine].
AB  - Microdeletions in AZF (Azoospermia Factor) region of the Y Chromosome have been
      recently described in azoospermic or oligozoospermic men. A Y chromosome
      molecular analysis was performed in peripheral blood DNA obtained from 16
      azoospermic patients. Microdeletions within the interval 6 of the long arm of
      chromosome Y were analysed using the PCR (Polimerase Chain Reaction) technique.
      The presence of the DAZ (SY255) sequence was tested in 6 patients, while the
      remaining 10 patients were analysed for 6 different loci mapped to AZFb and AZFc
      regions. Microdeletion was detected in one azoospermic patient in the YRRM2
      sequence. This result supports the finding of microdeletions not involving the
      DAZ sequence and suggests that routine investigation of azoospermic patients for
      microdeletions spanning the interval 6 region of y chromosome is also required.

PMID- 9616990
TI  - [How much competence in biomedical technique and medical physics do we need?].

PMID- 9616991
TI  - [Computer-based determination of red/green color vision defects].
AB  - A commonly used method of investigating colour vision, that is, the ability of
      the human visual system to discriminate colours, is based on the use of
      isochromatic colour plates, such as those used in the Ishihara test. The present
      paper describes a new computer-based method of determining red/green colour
      vision deficiencies. The method involves the presentation of Ishihara colour
      plates on a computer monitor. It has been verified experimentally that, despite
      the differences between the spectral emission of the computer screen and the
      daylight reflected by the Ishihara plates, the method is capable of
      distinguishing between subjects with from those without colour vision
      deficiencies. For screening purposes, the use of a reduced number of plates is
      suggested. This suggestion makes use of nine instead of 14 plates, and the
      criterion of two incorrectly recognized plates to determine a colour vision
      deficiency.

PMID- 9616992
TI  - Transcranial optical spectroscopy--A comparison of the TOS 96 and INVOS 3100
      cerebral oximeters.
AB  - We evaluated two user-friendly, commercially available transcranial cerebral
      oximeters (TOS 96, Tostec, Tokyo, Japan and INVOS 3100, Somanetics, Troy, USA)
      for use in adults. We compared the absolute values (%) of regional cerebral
      oxygen saturation (rSO2) from 108 measurements in 54 healthy volunteers (31
      women, mean age 35.8 +/- 16.3 years and 23 men, mean age 35.4 +/- 9.2 years). The
      mean rSO2 values obtained by the TOS 96 and INVOS 3100 systems were 72.3 +/- 8.4
      % and 72.6 +/- 7.2% respectively. Significant differences (p < 0.01) were found
      between females and males with the INVOS equipment. The study shows that
      anatomical (thickness of the skull) and technical (calibration) aspects have to
      be taken into consideration when interpreting absolute rSO2 values.

PMID- 9616993
TI  - [Model for simulation of heat loss by premature infants].
AB  - A prerequisite for the further improvement in the quality of warming therapy is
      an accurate knowledge of the interactions between the microclimate in warming
      therapy devices and the thermal balance of the infant. For generating this
      knowledge, thermal manikins can be helpful. Suitable models capable of also
      simulating evaporative heat loss in preterm infants have, however, not been
      available to date. A thermal manikin representing an infant weighing 530 g and
      capable of simulating convective, radiative and also evaporative heat loss has
      now been developed. It comprises an outer shell made of porous, anatomically
      shaped clay, and is divided into six compartments each of which can be heated
      individually. Water-filled Gore-Tex bags located immediately beneath the shell
      are provided to simulate evaporation. In a clinical study, temperature profiles
      of 8 very small preterm infants were measured thermographically. Measurements in
      the manikin showed that highly comparable temperature profiles with only minor
      differences could be obtained. Total heat and water losses by the manikin were in
      good agreement with clinical values. Using the model described here it is
      possible to simulate the heat exchange of premature infants under extreme and
      accurately reproducible environmental conditions. This manikin may thus serve as
      a tool for comparative studies, for the development of warming therapy equipment,
      or for training purposes.

PMID- 9616994
TI  - [Biomechanical analysis of arch-guided molar distalization with super-elastic
      nickel-titanium springs].
AB  - The typical characteristics of orthodontic devices and their effectiveness during
      tooth movement are of major importance for the success of orthodontic treatment
      and the stability of the result. To investigate this situation, two typical tooth
      movements were simulated experimentally using an Orthodontic Measurement and
      Simulation System (OMSS). These were Distalisation of an upper last molar and
      Distalisation of a molar including fixation of the guiding arch to a distal
      supporting last molar. The movements were simulated by employing various
      different NiTi coil compression springs and two standard steel guiding arches
      with the dimensions 0.016" x 0.022" and 0.017" x 0.025". The six NiTi springs
      differed significantly in shape and force characteristics. The eccentric
      application of the orthodontic force system relative to the centre of resistance
      brings about a tilting of the tube and arch via molar rotation. Although the
      forces developed by the springs are relatively constant, frictional losses result
      in variations in the effective orthodontic forces. With progressive
      distalisation, the average frictional losses varied between 50% and 80% of the
      spring-generated force, and frictional variations increased. Lower frictional
      losses were seen with a 0.016" x 0.022" guiding arch as compared with one
      measuring 0.017" x 0.025". In comparison with distalisation of a last molar,
      fixation of the arch to a third molar was associated with higher frictional
      losses. The interaction of the springs with the tube-guiding arch system could be
      so powerful that frictional losses were detected already during the initial phase
      of movement, and in extreme cases led to cessation of distalisation. The rate of
      distalisation was not affected by the forces generated by the springs. For
      physiological reasons, therefore, springs developing smaller forces should be
      used preferentially.

PMID- 9616995
TI  - [Polyethylene in total endoprosthetics--a dead end for permanent implants?].
AB  - Faced with a growing number of younger patients in need of total joint
      arthroplasty, orthopaedic surgeons are demanding long-term implants for total
      joint replacement. An assessment of the long-term mechanical behaviour is vivo of
      all biomaterials in common use in prostheses is in progress. In the present
      paper, we discuss the long-term reliability of polyethylene (UHMWPE) in joint
      replacement in terms of tribology and the different biomechanical situation in
      various human joints. Long-term failure mechanisms for polyethylene in total hip
      arthoplasty (THA) differ from those seen in total knee arthroplasty (TKA)
      although the same materials are used. It is thus questionable whether
      improvements in wear rates of polyethylene in THA would be helpful in TKA.

PMID- 9616996
TI  - Quality in the fast lane.
AB  - Dentistry, being a profession, must consider the important concept of quality
      control. Quality is the icing on the cake. With quality, patients will feel their
      visit to the practice has been a success. Defining which elements of practice
      merit assessment might be the starting point if the job is to be well done.

PMID- 9616997
TI  - Prescription of methotrexate.

PMID- 9616998
TI  - Advances in periodontal diagnosis. 9. Potential markers of cell death and tissue
      degradation.
AB  - This paper describes the potential markers of cell death and connective tissue
      degradation which might serve as markers of periodontal disease activity. The
      first section deals with enzymes released by dead and degenerating cells.
      Firstly, it describes how these pass from the periodontal tissues into gingival
      crevicular fluid (GCF) and explains that these enzymes have been used as markers
      of cell death in medicine for several decades. It then discusses the main enzymes
      in this group, aspartate amino transferase (AST) and lactate dehydrogenase (LDH)
      and reviews those studies which have attempted to relate these enzymes to
      periodontal disease severity and activity. Secondly, it describes the potential
      markers of connective tissue degradation, fibronectin, hydroxyproline-containing
      peptides and glycosaminoglycans (GAGs) and explains how these are produced.
      Finally, it describes the only commercial test kit for markers in this group (GCF
      AST).

PMID- 9616999
TI  - Dental manpower: many questions, weak data and inadequate answers.
AB  - The 1980s saw much discussion about manpower needs in many spheres of British
      life, including dentistry. There have been several manpower reviews since then,
      culminating in the closure of two UK undergraduate dental schools in the past
      decade. However, since then the number of vacancies in general dental practice
      appears to have doubled and there has been increasing difficulty obtaining dental
      associates. There appear therefore to be some manpower problems in general
      practice. Some of the available manpower data to the end of 1995 are examined and
      possible factors underlying these trends are considered, raising more questions
      than answers but suggesting the time has come to seriously review the situation.

PMID- 9617000
TI  - The effectiveness of acupuncture in treating acute dental pain: a systematic
      review.
AB  - OBJECTIVE: Acupuncture is frequently advocated as an effective treatment of
      dental pain. The question whether or not it is effective for this indication
      remains controversial. The aim of this systematic review therefore was to assess
      the effectiveness of acupuncture in dental pain. DATA SOURCES: Four electronic
      databases were searched: Medline, Embase, CISCOM, and the Cochrane Library. Only
      controlled trials were included in this review. DATA EXTRACTION: Information was
      extracted from included studies and entered on standard forms independently by
      both authors. Methodological quality was assessed using the Jadad score. MAIN
      RESULTS: 16 such studies were located. The majority of these trials imply that
      acupuncture is effective in dental analgesia. However, important questions remain
      unanswered. CONCLUSION: It is concluded that acupuncture can alleviate dental
      pain and that future investigations should define the optimal acupuncture
      technique and its relative efficacy compared with conventional methods of
      analgesia.

PMID- 9617001
TI  - Clinical assistant training in orthodontics--how effective is it?
AB  - OBJECTIVE: To investigate the quantity and the quality of orthodontic treatment
      carried out by dentists who have completed a 2-year orthodontic clinical
      assistant training programme. DESIGN: Retrospective analysis. SUBJECTS AND
      METHODS: During a 12-month period the volume of orthodontic treatments completed
      by 18 dentists who had participated in a clinical assistant training scheme was
      analysed. Using study models the initial need for treatment and the outcome of
      treatment of a consecutive sample of each dentist's completed cases were
      assessed. MAIN OUTCOME MEASURES: IOTN and PAR indices used by expert examiners.
      RESULTS: The median number of cases treated by the dentists was 37 with a range
      of 2 to 488. No significant predictive variables were associated with the higher
      volume operators. Of the 166 orthodontic cases evaluated 72.9% had a definite
      dental health need for orthodontic treatment. Following treatment the mean post
      treatment PAR score for the whole sample was 9.2 (median = 8.0). Thirteen (72%)
      of the dentists had an average post-treatment PAR score of 10 or less.
      CONCLUSIONS: The outcomes achieved by the Northern Irish clinical assistants were
      similar to those reported for other clinical assistant schemes. A significant
      proportion of the dentists treated a relatively low volume of patients and two of
      the dentists treated a very high volume of cases.

PMID- 9617002
TI  - A cross-sectional study of the oral healthcare instruction given to nurses during
      their basic training.
AB  - OBJECTIVE: To ascertain the current nurse training establishments' (NTEs')
      commitment to the teaching of oral care, and its coverage in nursing literature.
      DESIGN: Cross-sectional. SETTING: All NTEs in the UK for 1996/97 SUBJECTS AND
      METHODS: Self-completion questionnaire sent to all 162 Directors of Education of
      NTEs in the UK. MAIN OUTCOME MEASURES: A subjective assessment of the adequacy of
      the coverage of oral care in syllabi offered as part of nursing training; a
      subjective assessment of the relevance of literature recommended for student
      reading. RESULTS: 72% (117) responded. 27% (32) were post-registration NTEs not
      teaching oral care. The remaining 85 completed questionnaires were analysed. 79%
      (67) of these had no dental input; 75% (64) would welcome some. 28% (24) taught
      the use of an oral care assessment form; 38% (32) discussed dental plaque. 38%
      (32) had no exclusive lectures on oral care. Of 31 textbooks, only 1 had
      comprehensive coverage of the subject. The majority scored less than 25% on the
      assessment system. CONCLUSIONS: Many NTEs have oral care syllabus deficiencies.
      Students are recommended books which have insufficient information to provide an
      insight into oral care or dental disease. There would appear to be an urgent
      requirement for the nursing and dental professions to liaise in order to remedy
      this situation.

PMID- 9617003
TI  - [Social medicine in theory and practice].

PMID- 9617004
TI  - [Laudatio for Prof. Dr. Dr. Klaus Dorner on presentation of the Salomon-Neumann
      Medal of the German Society of Social Medicine and Prevention].

PMID- 9617005
TI  - [Acceptance address on presentation of the Salomon-Neumann Medal of the German
      Society of Social Medicine and Prevention on the congress topic "Social Medicine
      in Theory and Practice 29 September 1997 in Schwerin].

PMID- 9617006
TI  - [Structural and normative problems in recording medical facts in a structured
      social security system].
AB  - Medical expertising in the German structured social security system suffers from
      the fact that uniform standards and conditions have been worked out so far only
      very inadequately. The on-target accuracy of medical expertises is also hampered
      by the fact that experts are not sufficiently aware of the targets set by the
      various security systems. Sociomedical knowledge is hardly incorporated in the
      expertises. Due to the general lack of criteria and proportions the expert
      becomes the personal fate of the person to be expertised. This could be remedied
      in several ways: by improving the concepts laid down in section 96 of the German
      Social Code Book 10 as well as by a greater standardisation of medical services
      and last but by no means least by including "expertising" in the curriculum of
      the study of medicine at universities.

PMID- 9617007
TI  - [Target agreements between insurance carriers and hospitals as instrument for
      modifying hospital length of stay].
AB  - In 1995 the statutory sickness fund (AOK) in Magdeburg arranged target agreements
      with 10 of 23 acute care hospitals in its district to exercise an influence on
      the development of the average length of hospital stay. With the aim of
      decreasing the length of stay as well as the administrative cost and effort,
      these agreements set upper limits on the average length of stay which were
      hospital-specific and period-specific. In return, with only a few exceptions, the
      AOK Magdeburg refrained from limiting the coverage of individual cases. Hospital
      cases discharged from 1994 and 1996 were analysed to determine whether the
      development of the length of stay in the ten hospitals with target agreements
      differed from that in the other 13 hospitals. Only some of the hospitals were
      successful in reaching their target agreements. The average length of stay
      dropped by 4.2% in the hospitals with target agreements and by 7.9% in those
      without target agreements. This must be considered in the context of the
      development of the case load and number of available hospital beds. For instance,
      in spite of a target agreement, one hospital showed a (compensatory) increase in
      the average length of stay in association with an increase in the number of
      authorized beds and a concurrent decrease in the number of cases. The number of
      days billed by AOK patients per authorized bed (as an indicator of hospital
      productivity) showed a more favourable development in the group of hospitals with
      target agreements than in the other group. This was not a controlled trial as far
      as the selection of the hospitals is concerned. The results suggest that there is
      no harm in incentives that induce hospitals to manage primarily on their own the
      average length of stay. The use of routine aggregate data in monitoring this
      development, rather than the current more expensive individual case approach,
      also seems reasonable. Well planned studies that further test the "tool" of
      target agreements can be recommended.

PMID- 9617008
TI  - [Community health promotion policy for women by health reports?].
AB  - It is the declared aim of any national health policy to assist in the development
      of life styles and environments, in cooperation with other institutions, that
      would promote the overall health of the population. The Federal German provincial
      ("Land") governments and municipal as well as county administrations have been
      preparing health reports for this purpose during the last few years. The question
      is whether these reports adequately ensure the promotion of health among women in
      particular. Our conclusion is that this is not yet the case. The purpose of the
      following article is to describe and assess the present state of the problem and
      policy formulation. To this end we evaluated and synopsized 16 provincial and
      urban reports via document analysis. The health reports show that, although they
      do include problem definitions in relation to the health situation of women, they
      fail to formulate health targets for them. The reports are neither coordinated
      with health policy executives, nor do public health administrations cooperate
      with any other sectors of the administration to formulate and translate into
      reality a policy that would promote the health of women. On assessing the health
      reports in respect of their ranking within the Public Health Action Cycle for a
      health-promoting policy we must conclude that in their present form they are
      unsuitable both for defining health promotion problems and for formulating health
      policies with particular reference to women as an important target group. These
      health reports, as they are now being prepared and presented, lack clear
      definition and orientation with regard to appropriate action.

PMID- 9617009
TI  - [Neurorehabilitation: what it used to be, what it is, how will it be?].
AB  - Although neuro-rehabilitation has found its identity, it needs close relationship
      to general rehabilitation and the other disciplines. In particular, however,
      there is a close relationship to geriatric rehabilitation. Within the framework
      of a continuous, non-interrupted rehabilitation chain many goals have already
      been attained and some have been pinpointed as important future aims. My own
      contribution to this has been the follow-up rehabilitation service which should
      also be adopted in nursing homes for the elderly or the incapacitated. What is
      essential is the phase-specific utilisation of all measures, including integrated
      psychotherapy. Translation into organisational measures requires activities on
      many levels, including also the political level. This, however, involves the use
      of assessment instruments which are at present being introduced on the market
      with newly developed graduations. Medication and electronics have enabled us to
      achieve a few aims, and we expect that even more may be realised in the future.

PMID- 9617010
TI  - [How does the quality of life of long-term hospitalized psychiatric patients
      change after their discharge into the community?].
AB  - In the Berlin deinstitutionalisation study, quality of life in 134 long-term
      hospitalised psychiatric patients was examined twice: Discharged patients were
      interviewed again one year after their return to the community, whereas patients
      who continued to be hospitalised were reinterviewed after 1(1/2)-2 years after
      the first interview. Quality of life was assessed by the Berlin Quality of Life
      Profile. Four groups were distinguished in the analysis: 1. patients who
      continued as inpatients in the same hospital, 2. patients who had been referred
      to other hospitals, 3. patients who had been discharged after less than one year
      of continuous inpatient care, and 4. patients discharged after more then one year
      of hospital care. The four groups differed significantly in several
      sociodemographic and illness-related variables. Regarding the objective quality
      of life data, the four groups differed significantly in respect of the spheres
      leisure, social contacts and safety at follow-up. Discharged patients had more
      leisure activities, more often a "good friend", and more frequent social contacts
      within the last week. They had been less often victim to a crime. In a cross
      sectional analysis, the four groups showed significant differences regarding
      subjective quality of life in the spheres accommodation and safety. In a
      longitudinal analysis, no group showed any significant negative changes. Positive
      changes were found in the group of patients formerly hospitalised for more than a
      year most often: satisfaction with leisure activities, with the financial
      situation, and with accommodation improved significantly during the follow-up
      period. Results show a marked and significant improvement in the objective and
      subjective quality of life indicators in formerly long-term hospitalised patients
      after discharge.

PMID- 9617011
TI  - [Changes in homes for the aged and nursing homes: functional impairments and
      behavioral disorders of residents are increasing].
AB  - Residents in homes for the elderly and in nursing homes suffer from physical and
      mental disorders that are prevalent far above average. In the course of the
      changes that are presently taking place in the German health care system there is
      now an increase in the number of mentally ill and severely impaired persons
      residing in old-age homes. Earlier epidemiological studies do not yield any
      conclusive predictions of changes in residential structures and hence in nursing
      care requirements. Two cross-sectional studies are presented on the prevalence of
      physical and mental diseases, daily and behaviour problems among residents of old
      age and nursing homes in Mannheim. There was a distinct increase in average age,
      functional impairment, depression and disoriented behaviour among residents in 12
      homes for the elderly in Mannheim conducted in 1988 (n = 542) and 1992 (n = 497).
      During the period it was noted that disoriented behaviour significantly increased
      the mortality risk. In another study the by far larger group of nursing home
      residents was investigated. So far we have data for 1995 and 1996 on results
      obtained from 1178 residents of Mannheim homes for the elderly and nursing homes.
      Among the residents of nursing homes there was a much higher prevalence of
      functional impairment and behaviour problems than among those of homes for the
      elderly. Despite a very high prevalence of depression or disorientation, only
      every third resident was diagnosed as suffering from organic brain disease and
      only every tenth resident had a depressive disorder. Since a growing proportion
      of residents will be mentally ill or severely impaired, these institutions will
      be facing increasing medical and nursing demands. Due to limited resources, the
      homes cannot meet these demands adequately. Hence, health policy changes are
      mandatory to improve nursing care and to avoid placing an increasing burden on
      the nursing staff.

PMID- 9617012
TI  - [Physician practice patterns and attitudes to euthanasia in Germany. A
      representative survey of physicians].
AB  - Growing life expectancy and increasing pharmaceutical and technical methods in
      medicine are leading to more and more discussions among the general population
      and among physicians as to whether methods to shorten the sufferings of mortally
      ill persons should be legalised further. In Australia 60% of physicians wish to
      be able to perform active euthanasia if this would be legal. In the Netherlands
      physicians do not commit an offence if they perform euthanasia on the basis of
      ethically consented rules. In the FRG the National Board of Physicians
      (Bundesarztekammer) still rejects any liberalisation concerning active
      euthanasia. However, little is known of the attitudes and behaviour of physicians
      concerning the questions of active and passive euthanasia. Sponsored by Gruner
      and Jahr publishers for a magazine "Stern" publication we conducted a
      representative study among physicians working in hospitals and their colleagues
      in free practices concerning this topic. Beginning with qualitative interviews
      with 50 physicians we tested the questionnaire developed and looked for the data
      production method best fitting for this difficult matter resulting in telephone
      interviews or a self-administered questionnaire. In the main study a
      representative sample of n = 282 physicians in free practices and n = 191
      physicians in hospitals were interviewed. The response rates were 94% and 51%
      respectively. Analysis of non-responses did not indicate any bias. Half of the
      physicians think that a broader discussion on euthanasia is necessary, 34%
      disagree and 17% consider even a discussion already dangerous. 6% of the
      physicians in hospitals and 11% in free practices have already experienced
      methods of active euthanasia. Half of the physicians have seen patients who
      strongly wished euthanasia, a situation which happens once in every two years.
      The majority of physicians feel a deep understanding but only a minority of 4%
      comply with the wish. The vast majority of physicians advocate indirect
      euthanasia. However, they experience difficulties in defining the difference
      between active and passive euthanasia in a concrete situation. Summing up, our
      data indicate that a broader and open discussion on euthanasia seems necessary
      even if this discussion in Germany will be even more difficult than in other
      countries due to our recent past. The discussion will be reopened by a proposal
      on guidelines concerning euthanasia launched by the German National Board of
      Physician

PMID- 9617013
TI  - [From "reporting" to "surveillance": documentation of abnormalities within the
      scope of perinatal data collection--a sensitive instrument for monitoring new
      technologies?].
AB  - Analysis of the Hamburg perinatal quality assurance programme shows a dramatic
      increase in congenital abnormalities of the bones, joints and muscles from 45.29
      per 10,000 live births in 1990 to 106.32 in 1994. Comparisons with other
      perinatal quality assurance programme data reveal almost the same trend. In fact,
      there is no real increase in these specific congenital abnormalities, but there
      is an effect, which can be explained by the introduction of ultrasound hip
      screening in infancy signalling overdiagnostics due to the new technology. This
      example demonstrates that the perinatal quality assurance programme is a suitable
      instrument for registering congenital abnormalities and monitoring new
      technologies and interventions. These results support the proposal by the
      association of the leading state health officers (AGLMB) to use the already well
      established quality assurance programmes which are analysed on state level for a
      systematic nation-wide documentation and "surveillance" of congenital
      abnormalities. In addition, it becomes clear that surveillance, understood as a
      further development of health reporting, offers an opportunity to effect both an
      assessment and a better orientation in respect of health policies.

PMID- 9617014
TI  - [Poisoning in small children--assessing the incidence and intervention. II. What
      is effective in prevention?].
AB  - A study was started a) to assess the incidence self-poisoning in pre-school
      children and b) to evaluate the impact of an emergency set containing activated
      carbon and an antifoam. Cooperation was established with the regional legal
      sickness funds, the regional physician association, and two pharmaceutical
      companies. Incidence and extent of unintentional self-poisoning among pre-school
      children are to be determined. The impact of an emergency specimen given to
      parents of one year old children is evaluated. Families with children aged 1 to 4
      year living in boroughs of Berlin are the population at risk. Study period for
      measuring the incidence is from January 1995 to June 1998. Cases are all
      accidents of poison ingestion by children of the at-risk-population. Intervention
      was performed between July 1995 and June 1996. The sets were handed out to
      parents of children born in 1994. 85% of the selected parents could be
      interviewed. It was studied whether the behaviour of parents in accidents of
      poisoning differed between those given an emergency set compared to those who had
      none. Data were mainly collected by telephone interviews. In this paper the
      theoretical aspects of the psychological effect of the intervention are
      discussed.

PMID- 9617015
TI  - [25 years since the foundation of the Mexican Council of Gynecology and
      Obstetrics. Accomplishments and prospectives].

PMID- 9617016
TI  - [Simultaneous repair of type IV rectovaginal fistula (cloaca) and "ectopic anus"
      deformity. Presentation of a case and review of the literature].
AB  - A 40-year-old woman presented with a 7-year-old type IV rectovaginal fistula
      (cloaca) and an associated "ectopic anus" deformity. The initial step of the
      operation was the creation of two v-shaped full-thickness skin flaps.
      Subsequently, a longitudinal repair was performed. The initial elevation of the
      flaps facilitates the identification of muscular structures needing repair. The
      overlap of the flaps as a final step of the operation corrects the "ectopic anus"
      deformity. Critical steps of the operation are described in detail and
      illustrated.

PMID- 9617017
TI  - [Epidemiologic characteristics in women with sterility and cervical lesions with
      and without human papilloma virus infection. Comparative study].
AB  - Human papilloma virus (HPV) infections frequently cause cervical lesions of
      different morphologies. We have previously reported a 53.5% pregnancy rate after
      treatment in a group of women with infertility associated to HPV infection of the
      cervix uteri. In that paper it was stated that a controlled study should be
      conducted in order to confirm this finding. Present work was aimed to find if
      there is any correlation between HPV infections of the cervix uteri and
      infertility in a retrospective design using an historical cohort of patients
      studied between 1991 and 1996 in our clinic. A total of 61 women attending the
      Infertility Clinic at the Instituto Nacional de Perinatologia were included into
      two group. Group 1 (n = 45) included women with HPV lesions of the cervix and
      group II (n = 16) was formed by women with other type of cervical lesions who had
      no evidence of HPV infections on colposcopy. Cervico-vaginal citology,
      colposcopyc study and biopsy specimens were evaluated in all this medical records
      and the patients status (pregnant-not pregnant) at one year after treatment was
      registered. The mean duration time of infertility was 4.86 in group I and 3.5 in
      group II. Pregnancy rate was 16/45 (35.55%) in group I and 6/16 (37.5%) in group
      II. Seventy five percent of patients in group I and 66% in group II achieved a
      spontaneous pregnancy after specific treatment of cervical lesions whereas 25%
      and 33.3% required only ovarian stimulation with clomiphene or hMG. Pregnancies
      occurred approximately at 9 months after treatment in group I and at 7 months in
      group II. An association of cervical lesions and a tuboperitoneal factor
      (excluding endometriosis) was found on 53.57% of women in group I and on 46.66%
      of women in group II. Cervico-vaginal cytology was suspicious of HPV infection in
      less than 25% of cases. Present study emphasizes the need for a colposcopic study
      for the diagnosis of HPV infection in infertile women with cervical lesions even
      in cases with a negative cervico-vaginal cytology; because specific treatment of
      these lesions may yield spontaneous pregnancies. It also demonstrates that around
      50% of patients with cervical lesions have an associated tuboperitoneal factor,
      which indicates that it is mandatory to study the possible participation of viral
      infections on tubal pathology.

PMID- 9617018
TI  - [Uterine sarcoma. Analytic study of 37 cases].
AB  - The lack of uniformity in the nomenclature of the uterine sarcomas, it have
      contributed to a variety and variability of classifications. Fortunately the
      sarcomas of uterus are rare. The incidence of this tumor is of 3-5% of all the
      uterine cancers or of 1.7/100,000 women of 20 years or more. The clinical
      presentation of these tumors is diverse could come bleed uterine abnormal,
      abdominal pain, pelvic mass, discharge or cervix prominent mass. Clinical
      discoveries associated with exist the sarcomas how they are the obesity and high
      blood pressure in a 30% of the patients it are also observed antecedents of
      pelvic radiation in a 5-10% of the cases. The genomic alterations that is
      reported the chromosomes in the literature is associated with 1, 7 11 playing an
      important paper in the initiation or progression of the sarcomas. We was carried
      out a retrospective analysis of 37 cases of uterine sarcoma managed in the
      National Institute of Cancerology at one time of 5 years. Being that the
      leiomiosarcomas comes in the 51.3% of the cases, followed by the stromal sarcoma,
      bleed uterine abnormal it was the clinical fact of high importance, detecting
      these patients in Ia and IIa stadiums predominantly. We observed an increment in
      the incidence of the uterine sarcoma in patients of 40 years or more. 17 patients
      were managed exclusively with surgery, 17 patients with surgery and radiotherapy
      and 5 patients with surgery and chemotherapy (2 patients were managed with
      surgery + radiotherapy + chemotherapy). The index of failure was from the 45.1%
      to two years in general form, coming metastasic illness in lung, liver and breast
      mainly. In conclusion, the adjuvant radiotherapy and chemotherapy to the
      hysterectomy doesn't increase the index of survivor in the several subtype of
      uterine sarcomas.

PMID- 9617019
TI  - [Disappearance of the radiographic image of a macroprolactinoma after treatment
      with bromocriptine].
AB  - A young woman with amenorrhea-galactorrhea induced by a prolactin (PRL) secreting
      pituitary macroadenoma, was treated with bromocriptine 5 mg/day per os. Serum PRL
      levels were normal at 6 weeks and menstruation appeared at 8 weeks of treatment.
      When twenty months of treatment were completed, a tomographic study of the
      pituitary was unable to show any enlargement. Controversies related to
      macroprolactinomas treatment are discussed and it is suggested that treatment
      with dopamine agonists must be the elective treatment for patients with
      macroprolactinoma.

PMID- 9617020
TI  - [Itraconazole and secnidazole capsules vs. vaginal ovules of fluocinolone
      acetonide, nystatin and metronidazole in the symptomatic treatment of vaginitis].
AB  - OBJECTIVE: Evaluation of oral treatment in vaginitis and vaginosis using
      Itraconazol and sechidazol, in comparison to topic treatment using vaginal ovules
      of acetonido of fluocinolona 0.50 mg, nistatina 100,000 U and metronidazol 500
      mg. DESIGN: Longitudinal, prospective and open comparative study. PLACE: Servicio
      de Reproduccion Humana(Human Reproduction Department), Centro Medico Nacional "20
      de Noviembre". MATERIAL AND METHODOLOGY: Forty female patients, without any
      relevant differences in their general characteristics, chose diagnosis was
      vaginitis and vaginosis, who were medically treated through external
      consultation, divided in two groups of twenty each one. Group 1 oral treatment
      with itraconazol and secnidazol. Group 2 had topic treatment with fluocinolona,
      nistatina and metronidazol. All of the patients were controlled in seven and
      fourteen days time, in order to evaluate the intensity of their clinical
      symptomatology, as well as the efficacy in both ways of treatment. RESULTS:
      Leukorrhea was the most important symptom in all the cases, going from minor to
      serious white discharge. After the treatment, we found a relevant difference
      statistically significative in patients treated with intraconazol and secnidazol.
      We did not find any differences in relation to ardor, pruritus, dispareunia and
      disuria at post-treatment evaluation. However, group 1 betterment was
      statistically significative between the first and the seventh days of treatment.
      CONCLUSION: Treating vaginitis or vaginosis (or both) with itraconazol and
      secnidazol takes less time for betterment in addition to comfort and easiness of
      oral administration; therefore, we consider them proper medicines in these
      specific cases.

PMID- 9617021
TI  - Anatomy of a young suicide.

PMID- 9617022
TI  - Treatment of depression in general practice.

PMID- 9617023
TI  - Postnatal depression: diagnosis and treatment.

PMID- 9617024
TI  - Completing the coalition against dementia.

PMID- 9617025
TI  - Depression in terminally ill cancer patients.

PMID- 9617026
TI  - Antimicrobial resistance: a major threat to healthcare.

PMID- 9617028
TI  - The sick doctor scheme.

PMID- 9617027
TI  - Court reports and expert witnessing--getting it right!

PMID- 9617029
TI  - Dissemination and evaluation of AAP/AHA Neonatal Resuscitation Programme in
      Ireland.
AB  - We evaluated the need for a structured Neonatal Resuscitation Programme (NRP) by
      means of a questionnaire sent to 25 Irish maternity hospitals inquiring about
      staff availability and current teaching structures. Having taught NRP to almost
      1000 health care providers, we present a descriptive evaluation of the programme
      by a sample of 429 NRP participants, exploring their opinions of NRP. Our results
      show that midwives were responsible for newborn resuscitation at all low risk
      deliveries. Only 5 units (23%) had a registrar available on-site 24 hours a day,
      while the remaining units (77%) had to summon additional medical help from
      outside, in emergency situations occurring outside of normal working hours.
      Resuscitation equipment was checked by nurses alone (52%), or by a nurse and
      physician (48%), on a daily (45%), alternate days (41%) or weekly basis (14%).
      Although 19 units had some form of neonatal resuscitation training available,
      only 35% of respondents were happy with the current training structures. Almost
      half of the 429 providers (45%) replied to the survey. Most (85%) indicated that
      NRP improved their skills and confidence. Two thirds of participants found the
      lesson on medications the most difficult theory lesson, while 45% found
      endotracheal intubation the most difficult skills station. Because of the wide
      geographical distribution of deliveries in this country, we conclude that all
      perinatal professionals should be trained to perform newborn resuscitation in a
      coordinated, team-approach manner. NRP provides such training with a high degree
      of approval from Irish health care providers.

PMID- 9617030
TI  - Variation in suicide rates between Health Board areas.
AB  - This paper examines variations in suicide in the eight Health Boards of the
      Republic of Ireland for the years 1976 to 1995. It is found that while all have
      experienced a rise in male suicide, it has been much less pronounced in the
      Eastern Health Board which is somewhat surprising when one considers Dublin's
      much-publicised problems with homelessness and hard drug misuse. Since the mid
      eighties, female rates have been somewhat higher in the southern half of the
      country, comprising the Southern, Mid-Western and South-Eastern Health Boards.
      This variation may reflect a difficulty with contacting services for
      psychological distress in rural areas, either because of stigma or simple
      practical problems associated with transport. The development of appropriate
      services, especially in rural areas, should be at the top of the agenda of any
      Resource Officer to be appointed subsequent to the Final Report of the Task
      Force.

PMID- 9617031
TI  - Gamma-hydroxybutyrate (GHB): a new drug of misuse.
AB  - Accident and Emergency Departments offer a unique opportunity for identifying and
      monitoring new drugs of misuse. This series of six case reports describes the
      potentially serious medical complications associated with the use of gamma
      hydroxybutyrate (GHB) a new drug of misuse on the UK scene. Profound
      unconsciousness occurred in all cases and despite full (and often rapid) recovery
      all patients required medical intervention. Adverse effects occurred both when
      GHB was used alone or in combination with other illicit drugs and alcohol.

PMID- 9617032
TI  - Prospective evaluation of the utilization of aspirin and non-steroidal anti
      inflammatory drugs in acute medical admissions.
AB  - The aim of this study was to analyse the frequency of aspirin and NSAID usage in
      400 unselected patients admitted to the general medical wards through the
      Accident and Emergency Department. One hundred and twenty patients (30%) reported
      using NSAIDs (n = 27) or aspirin (n = 99) prior to admission. The median age was
      70.5 years (IQR 54-80). Most aspirin use was low dose for cardiovascular
      prophylaxis and headache. The reported indications for NSAID use were
      osteoarthritis (n = 12), rheumatoid arthritis (n = 9), gout (n = 3) and psoriatic
      arthritis (n = 2) and headache (n = 1). Only 23 (19%) patients were aware of the
      potential side effects of these agents. Co-prescribing with an H2 antagonist (n =
      10), proton pump inhibitor (n = 11) or misoprostol (n = 5) was noted in 21.6%.
      Approximately one third of patients admitted to general medical wards in this
      study were receiving NSAIDs or Aspirin. The indications for prescribing were
      appropriate for aspirin. NSAID use was more symptom based and may have been
      better managed using an analgesic in some cases. Despite the high prevalence of
      upper gastrointestinal symptoms, co-prescribing of ulcer healing drugs was
      relatively uncommon.

PMID- 9617034
TI  - Medical negligence: claims against doctors.

PMID- 9617033
TI  - A study of PSA requests from general practitioners received by one Dublin
      hospital.
AB  - Patterns of PSA requesting by General Practitioners were studied in one Dublin
      hospital for 11/1994-8/1995 and 11/1996-8/1997. 58% of requests (421/723) had PSA
      < 2ug/L and 82% had PSA < 4ug/L. Patients under 60 years accounted for 32% of the
      total requests but only 7% of these showed PSA levels over 4ug/L. PSA requests on
      these younger patients constitute a significant proportion of the PSA workload
      and yet appear to have low diagnostic yield. The mean age for all patients
      studied dropped from 68 years in 1994/1995 to 63 years in 1996/1997. This may
      reflect an increasing tendency to test all men over 50 years of age. This review
      of PSA requesting within our hospital's catchment area supports the view that PSA
      testing is not focused on higher risk individuals and shows tendencies towards a
      screening approach.

PMID- 9617035
TI  - Spontaneous rupture of the splenic vein in pregnancy.

PMID- 9617036
TI  - Mesothelioma of the tunica vaginalis--beware of the malignant hydrocoele.

PMID- 9617037
TI  - Seasonality as a determinant of the efficacy of praziquantel in population-based
      chemotherapy: lessons from the practice.
AB  - During October-November 1991, 1356 male farmers, 18-40 years old from a village
      in Fayoum Governorate, Egypt, were examined for Schistosoma haematobium
      infection. The prevalence of infection was 22.2%. Infected farmers were treated
      immediately with praziquantel at the recommended dose of 40 mg/kg body weight in
      a single, oral dose. Twelve weeks after treatment 86/262 (32.8%) infected farmers
      were negative for S. haematobium eggs in urine. In another study conducted in a
      satellite village in the Nile Delta (Beheira Governorate) where S. mansoni
      infection is prevalent, all residents of both sexes between 5 and 50 years of age
      (n = 858) were examined for S. mansoni. The prevalence of S. mansoni was 69.0%.
      Infected subjects were treated with the same dose of praziquantel during January
      February 94, with an overall resultant efficacy of 85.5% (471/551) and 97.2%
      (103/106) in 18-40 years old males 8-10 weeks post treatment. The high cure rate
      in the second study was probably because treatment took place 2 months after the
      end of the high transmission season.

PMID- 9617038
TI  - The prevalence and intensity of Schistosoma mansoni infection among residents in
      two Egyptian villages, at two and twelve months post-treatment with 40 and 60 mg
      praziquantel per kg body weight at these two villages respectively.
AB  - Two different regiments of praziquantel, 40 mg/kg in a single dose and 60 mg/kg
      in two divided doses administered 6 hr apart for the treatment of S. mansoni
      infection, were compared at two villages of Beheira Governorate. All residents of
      both sexes between 5 and 50 yrs old from two rural communities (Farshout and Om
      El-Laban) participated in this study. The prevalence of S. mansoni infection was
      58% at Farshout and 69% at Om El-Laban. Infected subjects received 60 mg/kg of
      praziquantel in two divided doses 6 hr apart at Farshout and 40 mg/kg in a single
      dose at Om El-Laban. Two months post-treatment, better cure rates (96% vs 85%, P
      < 0.001) were achieved with 60 mg/kg of praziquantel. Twelve months post
      treatment the prevalence of infection (45% for both villages) increased, but
      remained lower than before treatment. This may indicate that transmission
      continued from cercariae transported by water from nearby hyperendemic areas. The
      prevalence and intensity of infection were higher in the younger (5-19 y) than in
      the older (20-50 y) age group both before treatment and one year post-treatment.
      The same applies to the incidence and reinfection of the treated subjects. We
      recommend that 60 mg/kg in two divided doses six hours apart be used for school
      children. For logistical reasons, the single dose, 40 mg/kg regimen, should be
      used for mass treatment. For better control of disease, mass chemotherapy with
      praziquantel as suggested above is essential for the whole endemic region rather
      than only for a focal area.

PMID- 9617039
TI  - The quantitative buffy coat capillary tubes versus thin and thick blood films in
      the diagnosis of malaria in Saudi Arabia.
AB  - The Quantitative Buffy Coat (QBC) capillary tube was compared with both the thin
      and thick films in the diagnosis of malaria among three groups of hospitalized
      patients. Group (1) comprised subjects with no symptoms or signs, group (2)
      comprised patients with fever and rigors of unknown cause, and group (3)
      comprised treated malarial patients consulting the hospital for a follow up. The
      QBC test showed more sensitivity than the two conventional methods in the three
      groups as follows: in group (1) the QBC was positive in 14.2% compared to 9% only
      in either thin or thick blood films. In group (2) the positivity was 95.1%
      compared to 79.3% & 76.8% in the thin and thick blood films respectively. In
      group (3) the sensitivity was 22.9% compared to only 5.7% in both of the thin and
      thick blood films. The authors found that the QBC technique in addition to its
      high sensitivity is very practical, reliable, simple and easy to perform. No
      doubt, the thin blood film still the method of choice in species identification
      of malaria parasites.

PMID- 9617040
TI  - Octreotide decreases connective tissue formation and improves vascular changes
      associated with hepatic schistosomiasis.
AB  - In clinical practice, Octreotide has its greatest impact in the management of
      bleeding varices. The present work is the first one which was undertaken to
      investigate the possible use of Octreotide as an antifibrotic agent and to study
      its effect on hepatic vasculature in Schistosoma mansoni infection. The material
      of this investigation consisted of two groups of albino mice (A&B) subdivided
      each, into normal control, infected control, Octreotide treated, Praziquantel
      treated and Octreotide with Praziquantel treated subgroups. Groups A & B were
      sacrificed at the 8th week and the 18th week post infection respectively. By
      analysis of the obtained results, Octreotide has induced reduction of the portal
      pressure, the weight of the spleen and the liver, the number of liver egg load,
      granuloma size and cellularity, and of the degree of hepatic fibrosis quantified
      by serum PIIINP, serum laminin and tissue collagen using sirius red dye assay.
      Moreover, the biochemical state of hepatocytes has been improved. The subgroups
      treated with Octreotide in association with Praziquantel revealed better results
      than the subgroups treated with Praziquantel alone. Data were analysed in terms
      of histological extent of liver fibrosis in sections stained with Masson
      trichrome and sirius red, hepatocytic and sinusoidal changes at an ultrastuctural
      level and by immunohistochemical demarcation of endothelial cells of blood
      vessels through the determination of factor VIII related antigen. The promising
      results detected in this study may encourage to further investigate the positive
      findings of this drug with the intention of its possible application on a
      clinical level.

PMID- 9617041
TI  - Studies on myiasis producing flies collected by bait traps at Al Marg (Qalyobia
      Governorate), Egypt.
AB  - Myiasis is a real welfare problem. As a disease, it affects man and animals. In a
      study of myiasis producing flies in Al Marg District, sixteen species of
      dipterous flies were trapped. The predominant species was Musca domestica
      followed by Lueilia sericata and the least abundance was Wohlfahrtia magnifica.
      The overall abundance was in Summer followed by Spring and the least was in
      Winter. The most attractive bait was liver for members of family Calliphoridae
      and meat for members of family Muscidae and Family Sarcophagidae.

PMID- 9617042
TI  - In vitro effect of ivermectin on the larvae of Lucilia sericata meigen in Saudi
      Arabia.
AB  - Myiasis or the infestation of the living, necrotic or dead tissues of the body of
      man or animals by the dipterous fly larvae is a world wide welfare problem.
      Consequently, control of these larvae attracted the attention of many authors. In
      this paper, the broad spectrum antiparasitic drug, ivermectin was used in-vitro
      against the larvae of the green bottle fly, Lucilia sericata. The LC 50 was found
      to be 9 ppm (0.76-1.5) and the slope function was 0.59. This means that
      ivermectin is a safe and very effective larvicide for L. sericata.

PMID- 9617043
TI  - Bionomics and laboratory transmission of Haemoproteus columbae Kruse by
      Pseudolynchia canariensis Maquart (Diptera: Hippoboscidae) to two bird hosts in
      Egypt.
AB  - Pseudolynchia canariensis succeeded to feed and survive normally on both
      Streptopelia senegallus and S. turtur. The feeding period, blood meal ratio and
      longevity of both male and female flies did not differ significantly (P > 0.05)
      from the corresponding values for the natural host Columba livia. Infection of S.
      senegallus with Haemoproteus columbae through flies bites, injection with either
      infected salivary glands suspension or infected macerated lung tissue of C. livia
      revealed a high parasitaemia levels accompanied with normal prepatent periods.
      However, in S. turtur low parasitaemia levels appeared after long prepatent
      periods when using the same course of infection with H. columbae.

PMID- 9617044
TI  - Myiasis caused by Cephalopina titillator (Clark) in slaughtered camels in Al
      Arish Abattoir, North Sinai governorate, Egypt.
AB  - The oestrid fly or the camel nasal botfly Cephalopina titillator (Clark) is an
      insect that causes health hazards in camels. No doubt, camels are very important
      livestock particularly in arid and semi-arid lands. In this paper, the monthly
      and seasonal prevalence of C. titillator larvae in slaughtered camels were
      studied. The rate of camel infestation was 25%. The highest prevalence month was
      October and the highest prevalence season was Autumn. The three larval instars
      were demonstrated in the infested camels. However, the 3rd instars were the
      predominant stage (60.59%), followed by the 2nd instars (30.58%) and then the 1st
      instars (8.83%). In general, some myiasis producers are zoonotic parasites.
      Nevertheless, the control of the adult C. titillator and its larval instars is a
      must for the sake of the animal and for the human welfare.

PMID- 9617045
TI  - Prediction of villages at risk for filariasis transmission in the Nile Delta
      using remote sensing and geographic information system technologies.
AB  - Remote sensing and geographic information system (GIS) technologies were used to
      discriminate between 130 villages, in the Nile Delta, at high and low risk for
      filariasis, as defined by microfilarial prevalence. Landsat Thematic Mapper (TM)
      data were digitally processed to generate a map of landcover as well as spectral
      indices such as NDVI and moisture index. A Tasseled Cap transformation was also
      carried out on the TM data which produced three more indices: brightness,
      greenness and wetness. GIS functions were used to extract information on
      landcover and spectral indices within one km buffers around the study villages.
      The relationship between satellite data and prevalence was investigated using
      discriminant analysis. The analysis indicated that the most important landscape
      elements associated with prevalence were water and marginal vegetation, while
      wetness and moisture index were the most important indices. Discriminant
      functions generated for these variables were able to correctly predict 80% and
      74% of high and low prevalence villages, respectively, with an overall accuracy
      of 77%. The present approach provides a promising tool for regional filariasis
      surveillance and helps direct control efforts.

PMID- 9617046
TI  - Susceptibility of Biomphalaria alexandrina to the plant Azolla pinnata and some
      herbicides in relation to infection with Schistosoma mansoni miracidia.
AB  - Molluscicidal activity of the herebicides 2,4-D and Graminol, as well as both
      extracts and dry powder of the plant Azolla pinnata were evaluated against B.
      alexandrina snails. It was observed that 2,4-D proved to be the most toxic
      compound among he tested ones, showing LC90 of 52 ppm after 24 h of exposure.
      Ethanol extract of Azolla showed the highest molluscicidal activity against the
      tested snails compared with the other extracts and dry powder (LC90 = 3300 ppm).
      Ethanol extract at 6600 ppm after 3 h of exposure killed 100% and 19.4% of S.
      mansoni miracidia and cercariae, respectively. The molluscicidal activity of 2,4
      D was not influenced by the presence of Azolla (900 plants/liter) for 7 days,
      while Graminol effect was significantly reduced. However, the infectivity of S.
      mansoni miracidia to B. alexandrina snails was not affected by Azolla existence.

PMID- 9617047
TI  - The histopathological picture of the liver of hamsters experimentally infected
      with Leishmania D. infantum on top of Schistosoma mansoni infection.
AB  - No doubt, double and triple infection in a patient is not an uncommon phenomenon
      in the Old World. Consequently, the histopathological picture of the liver of
      Syrian golden hamsters experimentally infected with Leishmania. d. infantum on
      top of pre-infection with S. mansoni was studied. The results showed that the
      liver was markedly affected by the concomitant infection than infection with
      either parasite alone. The superadded Leishmania infection caused the early
      appearance of cell necrosis and fatty changes. The schistosomal granulomas were
      rounded in shape and well circumscribed. However, they were smaller in size and
      less in number when compared with schistosomal control. Also, there was a
      comparative decrease in the number of their cellular constitutions but without
      changing in the cell types. The schistosomal granulomas were surrounded with a
      rim of amastigotes laden macrophages. On the other hand, the leishmanial
      granulomas, were irregular in shape but comparatively increased in size and in
      number on the behalf of the schistosomal granulomas. Their cellular constitutions
      comparatively increased as well. So, it is concluded that the L.d. infantum
      infection on the top of S. mansoni infection suppressed the schistosomal
      pathological picture in the liver of hamsters.

PMID- 9617048
TI  - Spatial analysis of lymphatic filariasis distribution in the Nile Delta in
      relation to some environmental variables using geographic information system
      technology.
AB  - Geographic information system (GIS) was used to analyze the spatial distribution
      of filariasis in the Nile Delta. The study involved 201 villages belonging to
      Giza, Qalubiya, Monoufiya, Gharbiya, and Dakahliya governorates. Villages with
      similar microfilarial (mf) prevalence rates were observed to cluster within 1-2
      km distance, then, clustering started to decrease significantly with distance up
      to 5 km (Pearson correlation coefficient = -0.98). the likelihood of negative and
      high prevalence villages being contiguous was very low (approximately 1.8%, n =
      612 village-pairs) indicating homogeneity in disease processes within the defined
      spatial scales. Of the villages located within 2 km from the main Nile branches
      (n = 46), 95% exhibited low prevalence. In addition, the spatial pattern of mf
      prevalence was shown to be negatively associated with annual rainfall and
      relative humidity, while it was positively associated with annual daily
      temperature. Average mf prevalence in warmer, relatively drier areas receiving 25
      mm of rain was significantly higher (3.9%) than that in less warmer but more
      humid areas receiving 50 mm of rain (1.6%) (P < 0.0001). Based on the results of
      the present study, GIS was used to generate a "filariasis risk map" that could be
      used by health authorities to efficiently direct surveillance and control
      efforts. This investigation identified some of the factors underlying filariasis
      spatial pattern, quantified clustering and demonstrated the potential of GIS
      application in vector-borne disease epidemiology.

PMID- 9617049
TI  - Effects of antimonial therapy on serum zinc, copper and iron concentrations in
      patients with cutaneous Leishmaniasis in Turkey.
AB  - The effects of cutaneous leishmaniasis (CL) infections on total content of the
      essential trace elements and alterations of these elements content during
      antimonial therapy, serum iron (Fe), copper (Cu) and zinc (Zn), were determined
      in 40 patients with CL. 32 healthy subjects were selected as control group.
      Pentavalent antimonial compounds (Glucantime) were given intramuscularly (20
      mg/kg/day) for three weeks in patients group. Serum Cu and Zn levels were
      determined by flame atomic absorption spectrometry and Fe levels were determined
      by colorimetrically. Before antimonial therapy; Cu levels were found
      significantly higher. However, Zn and Fe levels were found significantly lower in
      the patients group than those of controls. Cu levels were found tended to
      decrease, while Zn and Fe levels tended to increase during antimonial therapy.
      There was a negative correlation between serum Cu and Zn levels in CL patients (r
      = -0.322, p < 0.05). The findings showed that CL affects the essential trace
      element content and these changes began to disappear during antimonial therapy.

PMID- 9617050
TI  - Intestinal capillariasis as a cause of chronic diarrhoea in Egypt.
AB  - Intestinal capillariasis in humans is caused by a nematode- Capillaria
      philippinensis, which infects small fresh water or brackish fish and some fish
      eating birds. It has occurred in areas where people eat raw fish such as the
      Philippines and Thailand. This paper reports a case of a women with intestinal
      capillariasis in Menouf, in the Nile Delta of Egypt. It is the second case to be
      reported from the same area of Menouf. Microscopic examination of stool revealed
      eggs, larvae and adult male and female worms of C. philippinensis. This was
      successfully treated with Albendazole.

PMID- 9617051
TI  - A study on the relation between proton pump inhibitor and gastric giardiasis.
AB  - Thirty patients treated with proton pump inhibitor and still having symptoms
      related to gastritis or peptic ulcers were subjected to upper gastrointestinal
      endoscopy and gastric biopsy for detection of giardiasis in these cases. Results
      showed presence of 3 (10%) cases of gastric giardiasis, intestinal metaplasia and
      presence of H. pylori in these cases. It is concluded that there may be a
      relation between the presence of gastric giardiasis and the intake of proton pump
      inhibitor. The endoscopists have to search for gastric giardiasis especially in
      the presence of H. pylori and/or intestinal metaplasia.

PMID- 9617052
TI  - Immediate endoscopic injection therapy of bleeding oesophageal varices: a
      prospective comparative evaluation of injecting materials in Egyptian patients
      with portal hypertension.
AB  - The present study was conducted to compare usual sclerosants: polidocanol 1%,
      ethanolamine oleate 5% and the tissue adhesive: cyanoacrylate in the control of
      oesophageal variceal bleeding in Egyptian patients with portal hypertension in a
      prospective comparative trial. Sixty patients with portal hypertension due to
      schistosomal hepatic fibrosis and/or posthepatitic liver cirrhosis who had
      presented with acute oesophageal variceal bleeding were enrolled. Patients
      received balloon tamponade prior to injection were excluded. Resuscitation had
      been done before or during emergency endoscopy. Emergency endoscopy was conducted
      within 2 hours from the onset of hematemesis. Patients were immediately
      randomized during emergency endoscopy to receive polidocanol 1%, ethanolamine
      oleate 5% or tissue adhesive. Variceal rebleeding was managed by reinjection. The
      three groups were comparable for age, sex, etiology of portal hypertension, Child
      Pugh class and findings at emergency endoscopy. No active bleeding was observed
      at the end of all injection sessions. Rebleeding had been occurred within the
      first 24 hours in 2 (10%) patients in polidocanol group and 3 (15%) patients in
      ethanolamine group (P > 0.05). Reinjection did control rebleeding in 2 (10%)
      patients in ethanolamine group with a total success rate of 95%. Exsanguinating
      rebleeding occurred in 2 (10%) patients in polidocanol group and one (5%) patient
      in ethanolamine group (P > 0.05). Postinjection large ulcers were diagnosed
      either in polidocanol (15%) or ethanolamine (10%) groups (P > 0.05). Other
      complications were minor and showed no significant differences between the three
      groups. In coclusion, polidocanol, ethanolamine and cyanoacrylate are equally
      safe and effective. For immediate endoscopic injection therapy an experienced
      team must be available.

PMID- 9617053
TI  - Cellular constituent and intercellular adhesion in Schistosoma mansoni granuloma:
      an ultrastructural study.
AB  - The present work deals with the structural analysis of Schistosoma mansoni
      granuloma and the visualization of cellular interaction at an ultrastuctural
      level in the acute (8 weeks) and chronic (20 weeks) stages of infection, for more
      detailed understanding of pathophysiology of the disease. Although, S. mansoni
      granuloma is mediated by T-lymphocytes, yet in this work the macrophage cells and
      not the lymphocytes represented the main cell type in cellular and fibrocellular
      granulomas. The cellular and fibrocellular granulomas detected in the acute stage
      of infection elicited no difference in cellular constituent to those of the
      chronic stage respectively. Macrophage cells and fibrocytes were the only cell
      type detected in fibrotic granuloma. The monocytes may be considered the first
      cell reaching the site of the trapped egg as they formed the first row of cells
      around the egg. The cellular infiltrate forming the granuloma: monocytes,
      macrophages, lymphocytes, eosinophils, fibroblasts and plasma cells revealed
      direct contact or adherence between them and even between the individual cell
      type, through extending protrusion from the cell membrane of adjacent cells. They
      constituted an integrated network which encircled the egg. Similar adhesion
      between inflammatory cells in the blood vessels and between the inflammatory
      cells and the endothelial cells were displayed. These points of intercellular
      adhesion appeared as if, not only used for functional communication between the
      cells, but also for cellular deplacement either in the extracellular matrix or in
      the blood stream until extravasation. In conclusion, S. mansoni granuloma is a
      highly organized cellular lesion, in which cell to cell communication occurs
      through direct cell contact.

PMID- 9617054
TI  - Renal changes in golden hamsters experimentally infected with Leishmania D.
      infantum on top of Schistosoma mansoni infection.
AB  - In Egypt, Schistosomiasis mansoni is one of the most important parasitic disease
      of man. Besides, in the last two decades, indigenous cases of infantile visceral
      leishmaniasis have been reported. These two parasites affect the kidney causing
      renal histopathological changes. Thus, it was aimed to study the concomitant
      infection of L. d. infantum on top of S. mansoni infection in Syrian golden
      hamsters, the model animal for both parasites. The results showed that the renal
      changes were more or less the same as infection with either parasite alone. Both
      parasites produce mesangial cell proliferation and mesangial matrix increase.
      Some glomeruli showed complete replacement of the capillary tuft with
      structureless homogenous material. In one S. mansoni positive control hamster
      Schistosoma eggs were seen within granulomas and atrophic glomeruli. However, the
      lesihmanial infection, more or less suppressed the schistosomal infection. The
      leishmanial infection itself became more prominent and the renal changes it
      caused appeared earlier and were more obvious.

PMID- 9617055
TI  - Insecticidal and synergistic activity of Atriplex halimus L. extracts.
AB  - The acetone/ethanol, petroleum-ether, ether and chloroform extracts of Atriplex
      halimus L. proved to be with considerable toxicity to Culex larvae with LC50
      values of 115, 36, 54 and 48 ppm, respectively. Out of the different extracts of
      A. halimus, the ether and pet-ether extracts showed strong aphicidal activity
      against A. gossypii with LC50 values of 0.059 and 0.085%, respectively. Only the
      ethanol extracts were found to be toxic to the cotton leafworm with LD50 value of
      5.6 mg/larva. All of the tested extracts were non toxic to the stored product
      insect, T. castanum. Organo-phosphorous (OP) insecticides synergism studies
      revealed that the pet-ether and ethanol extracts of Atriplex strongly synergized
      the toxicity of reldan and actellic in Tribolium castaneum.

PMID- 9617056
TI  - Insecticidal, acaricidal and synergistic effects of soosan, Pancratium maritimum
      extracts and constituents.
AB  - In assessing the pesticidal activity of soosan, P. maritimum, the bulbs and
      leaves were extracted using acetone/ethanol & ethanol as solvents and mosquito
      larvae C. pipiens, as a test organism. The actone/ethanol extract of bulbs was
      more toxic (LC50: 25 ppm) than that of the leaves (LC50: 75 ppm). Crude
      alkaloids, lycorine, terpenes & sterols and fixed oil were isolated from soosan
      bulb. their percentages were: 0.193, 0.02, 0.13 and 3.3%, respectively. The
      acetone/ethanol extract showed a strong aphicidal activity to Aphis gossypii with
      LC50 of 0.028% followed by lycorine, soosan oil and crude alkaloids with LC50
      values of 0.07, 0.28 and 0.3% respectively. Also, the acetone/ethanol extract
      showed high toxicity to Spodoptera littoralis 4th instar larvae, with LD50 value
      of 2 Mg/larva. In addition, the crude alkaloids ethanol extract and the oil of
      soosan bulbs showed acaricidal activity against the two spotted spider mite,
      Tetranychus urticae with LC50 values of 0.2, 0.36 and 1.5%, respectively.
      Synergism studies on the A. gosspii indicated that lycorine, the principal
      alkaloid of soosan bulbs, strongly synergized, the OP insecticide cyanophos and
      reducing its LC50 values from 120 to 48 ppm. On the other hand, the aqueous
      extract of soosan bulbs synergized the toxicity of actellic and permethrin in
      Tribolium castaneum which reduced their LC50 values from 80 to 46 ppm and from
      1000 to 550 ppm, respectively. Also, ethanol and petroleum-ether extracts
      synergized the toxicity of reldan and permethrin, respectively, in the same
      insect.

PMID- 9617057
TI  - Efficacy of ivermectin on the infectivity of Leishmania major promastigotes.
AB  - Ivermectin is widely used as an antiparasitic drug for livestock and recently
      used for some human parasites. The effect of ivermectin on the infectivity of
      Leishmania major promastigotes was studied in Syrian golden hamsters. The results
      showed that hamsters infected with promastigotes treated for one day with 100
      micrograms/ml ivermectin in culture medium did not develop skin lesion at the
      site of infection. However, amastigotes were demonstrated in Giemsa stained
      splenic smears. On the other hand, promastigotes treated for two days with 90
      micrograms/ml ivermectin did not acquired the infection. i.e. the promastigotes
      died or lost their infectivity.

PMID- 9617058
TI  - Cyclospora: a newly identified protozoan pathogen of man.
AB  - A newly recognized protozoan human parasite, Cyclospora spp. has been
      incriminated as the cause of prolonged diarrhoea. It has been isolated from
      children, immunocompetent and immunocompromised adults. One hundred and thirty
      immunocompetent patients, 80 children and 50 adults; their illness was
      characterized by prolonged watery diarrhoea, were enrolled in this study. Stool
      sediments were examined as wet mounts and stained by both, modified Ziehl-Neelsen
      and aniline carbol methyl violet stains. The protozoan pathogen was identified as
      spherical bodies measuring 9-10 microns in diameter in about 9% and 10% in both
      children and adult groups respectively. The mean duration of illness was 28 +/- 8
      and 37 +/- 12 days and the frequency of stool motions was > 5/day with normal
      mucosal pattern on colonoscopic studies for adults group. It is concluded from
      the present study that cyclosporiosis is quite similar to cryptosporidiosis and
      both oocysts have the affinty to acid fast stain so the present recommendations
      for all laboratories screening stool for cryptosporidia should measure the oocyst
      to distinguish between these different parasites and there is obviously a great
      deal more to learn about this emerging protozoon.

PMID- 9617059
TI  - Role of pseudolynchia canariensis in the transmission of haemoproteus turtur from
      the migrant Streptopelia turtur to new bird hosts in Egypt.
AB  - Pseudolynchia canariensis flies offered the naturally infected migrant dove
      Streptopelia turtur with Haemoproteus turtur succeeded to induce weak infection
      in the raised Streptopelia turtur only. Intraperitoneal, intramuscular and
      subcutaneous injection of their salivary glands together with intraperitoneal
      injection of macerated lung and liver tissues of infected doves revealed the
      appearance of low and moderate grade parasitaemia in S. senegallus and the raised
      S. turtur. Flies offered laboratory infected donor doves of low and moderate
      parasitaemia could transmit the parasite through all the experimental trials
      during the course of infection with variable degrees of parasitaemia to both
      doves. All attempts to transmit H. turtur to Columba livia was unsuccessful.

PMID- 9617060
TI  - Studies on experimental mixed infection of Schistosoma haematobium and
      Schistosoma mansoni.
AB  - Swiss Albino mice have been infected with S. haematobium and challenged 4 weeks
      later with S. mansoni. Parasitological, pathological and ultrastructural studies
      were done. The results revealed cross mating between the two species. A reduction
      in S. mansoni worm load, egg count, hepatic granuloma number and size was
      noticed. The presence of heterologous immunity was suggested.

PMID- 9617061
TI  - Functional correlation between histamine metabolism and worm expulsion in
      Trichinella spiralis.
AB  - Mucosal mast cell activity was quantified by measuring histamine forming capacity
      (HFC) of the gastric mucosa and histamine content in the intestinal tissues of
      mice infected with T. spiralis. The results wee correlated with the kinetics of
      worm expulsion. It was found that T. spiralis resulted in significant elevation
      of HFC by the day 6 post infection (p.i.) which reached a maximal value at day 9,
      a time when approximately 50% of the established worm burden had been expelled.
      Histamine content of the intestinal tissues followed the same pattern. No
      intestinal worms were present by day 28 of infection and there was a gradual
      reduction in HFC and histamine content which had returned almost to control
      values by that time. Significant inverse correlation between individual worm
      burdens and HFC was detected.

PMID- 9617062
TI  - A new coccidian parasite (Apicomplexa: Eimeriidae) from the legless lizard
      Diplometopon zarudnyi (Amphisbaenia: Trogonophidae) in Saudi Arabia.
AB  - Large numbers of coccidian oocysts belonging to the genus Isospora were obtained
      from the intestinal contents of ten legless lizards Diplometopon zarudnyi
      collected from eastern region, Saudi Arabia. The oocysts are spherical to
      subspherical, 33.3 x 30.9 (28.6-35.2 x 26.8-32.7) microns with a bilayered wall
      1.4 (1.3-1.6) microns thick. Micropyle, polar granule and oocyst residuum are
      absent. The sporocysts are ellipsoid, 20.1 x 13.8 (17.5-22.3 x 12.2-15.4)
      microns. A sporocyst residuum, stieda and substieda bodies are present.
      Sporozoites are banana shaped, blunt at one end and tapered at the other and
      containing spherical anterior and posterior refractile bodies of the same size.
      Since this Isospora sp. does not resemble, any other species of Isospora
      previously described from lizards of the genus Diplometopon, it has been named
      Isospora diplometoponi n.sp. after the host generic name.

PMID- 9617063
TI  - Study of trichomoniasis among Egyptian male patients.
AB  - In the present study, Trichomonas vaginalis was diagnosed in 28.8% male patients
      with urethral discharge and in 8.2% suffering from impotence and infertility.
      Diagnosis was based on examination of urethral discharge, urine, semen and
      prostatic massage fluid by wet mount, stained films and culture inoculation.
      Diamond's culture proved to be the method of choice.

PMID- 9617064
TI  - Phlebotomus major syriacus: a possible vector of visceral Leishmaniasis in
      western Black Sea region of Turkey.
AB  - Two clinical forms of leishmaniasis have been observed in Turkey, cutaneous (CL)
      and visceral (VL) Unitl now, VL cases were firstly reported from two villages of
      Karabuk (western Black Sea region of Turkey). These villages have population of
      300, 1030 m altitude and high humidity due to long rain period. Initial
      entomological study was carried out in July 1996. A total of 123 sandflies (males
      and females) were captured using CDC light and sticky paper traps. Sandflies were
      collected from around wells and walls of houses and of animal shelters.
      Phlebotomus m. syriacus, found in rocky areas of high altitude and water bodies
      is the only species identified in the area and can be incriminated as the
      possible vector.

PMID- 9617065
TI  - Mutual effect of Schistosoma mansoni infection and pregnancy in experimental C57
      BL/6 black mice.
AB  - Sixty female C57BL/6 mice were infected with 40 Schistosoma mansoni cercariae
      each. Seven weeks later, they were mated with normal syngeneic males. Uninfected
      mice (30) were bred in parallel, and both groups were bred several more times
      with daily records of pregnancy, delivery and number of offsprings. The number of
      pregnancy was 146, with 50 survived infants (34.2%) in contrast to 121 pregnancy
      with 93 survived infants (76.8%) in controls. The outcome of pregnancy was 13%
      abortion, 10.9% maternal death and 41.7% infanticide. The weight of offspring at
      2 and 4 weeks of age was significantly less than in controls (P < 0.01). Again,
      C57BL/6 (40) female mice were mated, then infected with 100 S. mansoni cercariae
      each. The results showed that, pregnancy had no effect on bilharzial infection as
      the total worm burden and distribution, hepatic and intestinal tissue egg count
      and the oogram profile, were not significantly differ from that in the control
      group (20). Besides, the immediate footpad swelling was significantly higher but
      the delayed footpad swelling and the level of antibodies against S. mansoni
      soluble egg antigen were insignificantly differ from that present in the parallel
      control (infected but not pregnant). As regards histopathological parameters,
      although there was insignificant difference in the size of hepatic granuloma, yet
      there was more collagenous fibrous tissue deposition distributed in-between
      inflammatory cells specially at the periphery of the granuloma.

PMID- 9617066
TI  - Chemotherapy of Schistosomiasis present and past.
AB  - The primary objective of chemotherapy is to cure individual patient by
      eradication of the infection. This eradication leads to cessation of egg
      deposition which is the main pathogenic agent for the patient and community. The
      present generation of antischistosomal drugs provides physicians and public
      health practitioners with flexible, well tolerated, convenient, highly efficient
      tools for control of schistosomal morbidity in human, in contrast old generation
      of antischistosomal drugs were not so.

PMID- 9617067
TI  - Testimony before the House Commerce Committee: a smoke-free America.

PMID- 9617068
TI  - Cocaine use as a risk factor for abdominal pregnancy.
AB  - Failure to diagnose abdominal pregnancies can have disastrous morbidity/mortality
      consequences for mother and fetus. To make the diagnosis of abdominal pregnancy
      requires that the physician have a high index of suspicion and that he or she
      have a good understanding of the risk factors of abdominal pregnancy. This
      article presents data suggesting that maternal cocaine use is a risk factor for
      abdominal pregnancy, reviews the literature on the maternal/fetal effects of
      maternal cocaine use and the risk factors of abdominal pregnancy, and analyzes 55
      cases of abdominal pregnancy. Maternal cocaine use correlated with a 20% rate of
      increase in the incidence of abdominal pregnancy compared with the 70% rate of
      decrease in the "before cocaine" time period. Recommendations are offered for
      management.

PMID- 9617069
TI  - Youth counseled for HIV testing at school- and hospital-based clinics.
AB  - The prevalence of human immunodeficiency virus (HIV) in adolescents is difficult
      to assess as few adolescents consent to testing. This prospective study
      characterized urban youth requesting HIV testing at two types of health settings,
      inner-city school-based and hospital-based clinics. Data were obtained on 1652
      inner-city youths aged 13 to 19 years who consented to individualized HIV
      counseling and testing from January 1993 to January 1994. Identified risks for
      HIV included sexual activity, sexually transmitted disease (STD) history, and
      substance use by self-report during a confidential structured interview. Data
      were analyzed using chi-squared analysis. Of the 1652 youth who were counseled,
      1602 were from hospital-based clinics. A total of 827 (50%) requested HIV
      testing. Females accounted for the majority of youth who underwent counseling
      (79%) and requested HIV testing (75%). However, once counseled, males were more
      likely to be tested. Risk factors differed by gender; females were more likely to
      report STDs and marijuana use, and males more likely to report alcohol and
      cocaine use. These results indicate a need to identify developmentally
      appropriate methods to educate and counsel youth about HIV that will lead to more
      youth willing to be tested. School-based clinics may provide easier access than
      traditional health models for confidential HIV services.

PMID- 9617070
TI  - Prevalence of diabetes mellitus and impaired glucose tolerance in a group of
      urban adults in Nigeria.
AB  - This survey was undertaken to determine the prevalence of diabetes mellitus and
      impaired glucose tolerance in a group of urban adults in Ibadan, Nigeria. A total
      of 998 subjects randomly selected from five main ministries and departments in
      the Government Secretariat participated in the survey. Each subject was asked to
      fast overnight and ingested 75 g of glucose dissolved in 250 mL of water after
      answering a questionnaire. Relevant anthropometric measurements such as weight,
      height, waist and hip diameters, and blood pressure also were taken. After 2
      hours, of blood was drawn and plasma glucose concentration measured. Diagnosis of
      diabetes or impaired glucose tolerance was based on 1985 World Health
      Organization (WHO) cut-off values. Blood glucose results were available in 875
      subjects. Seven subjects were found to be diabetic for a prevalence of 0.8%, with
      the majority (5 subjects) being newly diagnosed. Nineteen were found to have
      impaired glucose tolerance for a prevalence of 2.2%. There were no sex
      differences between the two groups. All of the newly diagnosed diabetics were
      asymptomatic. Multivariate analysis revealed that subjects with a family history
      of diabetes, higher body mass index, and higher systolic blood pressure had
      higher blood glucose levels. The prevalence of diabetes in this survey is lower
      than rates reported in recent surveys in Nigeria that used less stringent
      criteria and different methodologies. The rate is comparable to that of a
      Tanzanian study that used WHO criteria. However, the rate of impaired glucose
      tolerance in this study, first to be reported in Nigeria, is lower than that
      obtained in the Bantu population.

PMID- 9617071
TI  - Clinical determinants of survival from stage Ib cervical cancer in an inner-city
      hospital.
AB  - This study reviewed a high-risk population of inner-city women with FIGO
      (International Federation of Gynecologists and Obstetricians) stage Ib cervical
      cancer diagnosed and treated at a single institution between 1986 and 1993. The
      patient age at diagnosis averaged 49 years, and most of the patients were black
      (83%). Squamous carcinomas predominated (75%). Radiotherapy was the most frequent
      treatment modality (49%), followed by surgery (38%) and combined
      radiation/surgery (13%). The Kaplan-Meier estimated 4-year survival for all
      patients completing treatment was 81%. Increased survival was significantly
      associated with therapy. The Kaplan-Meier estimated survival at 26 months (the
      time of the last death in radiotherapy patients) was 66% for radiotherapy
      patients and 100% for those treated with surgery. Radiotherapy patients differed
      from surgery patients in age, tumor size, and pelvic lymph node status,
      indicating that treatment selection bias could explain the observed difference in
      survival. Age, race, histology, and cervical lesion size were not significantly
      associated with survival.

PMID- 9617072
TI  - Retrospective on community dentistry and public health at the University of
      Southern California (1966-1976), Part 2.
AB  - The authorization of departments of community dentistry and public health in the
      nation's dental schools is a relatively recent innovation in dental education.
      Such a department was established at the University of Southern California School
      of Dentistry in 1966, as part of the School of Medicine's effort to share
      responsibility in providing both access and availability of health services in
      inner-city Los Angeles, California. Dentistry was included in the protocol
      submitted to the US Office of Economic Opportunity to build a neighborhood health
      center in Watts, operated under the joint jurisdiction of the medical and dental
      schools. The dental division of the health center was designated a satellite of
      the community dentistry department. The department envisioned future changes
      during the revolutionary 1960s when all aspects of the nation were experiencing
      upheaval as traditional concepts were challenged by new attitudes. The nation's
      leaders in government and education as well as in the health professions were
      stimulated by scientific and technologic discoveries. Dentistry had come of age,
      having gained the respect of other health-care disciplines. It was a time of
      expanded exploration of means toward a healthier populace and a more sensitive
      ethical provider of health care. In one decade, the USC community dentistry
      department accomplished a major shift in attitude about the specialty from one of
      pervasive opposition and antipathy to that of acceptance and even enthusiasm. The
      department became competitive with similar units nationwide in educating dental
      students and practitioners to fulfill their responsibilities at the highest level
      of proficiency and to be true to the trust bestowed on them by the public. In
      pursuit of these goals, the department reflected credit on dentistry and the
      University of Southern California.

PMID- 9617073
TI  - Hemoperitoneum in a postmenopausal woman.
AB  - As the number of postmenopausal women increases, physicians will have more
      opportunities to treat elderly women with gynecological complications. This case
      report describes a 76-year-old, obese, multiparous woman, known to have
      gallstones who presented with acute abdomen complaints and was admitted for
      observation. Treatment was delayed until significant blood loss was recognized.
      At laparotomy, a ruptured ovarian granulosa cell tumor was found.

PMID- 9617074
TI  - Intermediate epithelium.
AB  - In the nasopharynx, the larynx, the anal canal and the auditory tube, the
      "intermediate epithelium" occupied the transitional zone between the ciliated (or
      nonciliated) columnar epithelium and the stratified squamous one. The
      intermediate epithelium showed gradations ranging from stratified low-columnar
      through stratified cuboidal to stratified squamous type. It was suggested that
      the intermediate epithelium showed the various stages of the epithelium
      transforming from the columnar to the squamous epithelium, and that the basal
      cells of the columnar epithelium served as the germinal layer of the
      transformation.

PMID- 9617075
TI  - Synaptic connections between the prefrontal cortex and the mediodorsal nucleus of
      the thalamus.

PMID- 9617076
TI  - [Cytoskeletal proteins related to intracellular membrane dynamics].

PMID- 9617077
TI  - [The mechanisms of corticoids biosynthesis revealed by immunohistochemistry and
      in situ hybridization].
AB  - The improvement of immunohistochemistry and in situ hybridization techniques has
      recently allowed a prominent advancement in morphological research on the
      mechanisms of steroid-hormone biosynthesis in the adrenal gland. Cholesterol side
      chain cleavage enzyme (P450scc) was localized in the inner mitochondrial membrane
      of all cortical cells. Steroid 3 beta-hydroxysteroid dehydrogenase/delta 5-4
      isomerase (3 beta-HSD) and 21-hydroxylase (P450c21) were present in the membrane
      of smooth endoplasmic reticulum (SER) of all cortical cells. 17 alpha
      Hydroxylase/C17-C20 lyase (P45017 alpha) was located in the SER membrane of the
      zona fasciculata-reticularis cells of human, bovine, swine, guinea-pig, and
      hamster adrenal gland. This enzyme, however, was absent in the adrenal gland of
      rat, mouse and rabbit. 11 beta-Hydroxylase (P45011 beta) and aldosterone synthase
      (P450aldo) were situated in the inner mitochondrial membrane of the zona
      fasciculata-reticularis cells and in that of the zona glomerulosa cells,
      respectively. These results indicate that aldosterone is synthesized in the zona
      glomerulosa cell, and that glucocorticoids such as cortisol and corticosterone
      are synthesized in the zona fasciculata-reticularis cells. The conversion of
      cholesterol to pregnenolone and the final steps of corticoids synthesis occur in
      the mitochondria, while the intermediate steps, leading to the synthesis of
      deoxycorticosterone or deoxycortisol from pregnenolone, take place in the SER
      membranes.

PMID- 9617078
TI  - [Morphological basis on periodontal Ruffini endings].
AB  - The periodontal ligament has a rich sensory nerve supply which serves as a
      sensory apparatus in addition to tooth support. The periodontal ligament contains
      nociceptors and low-threshold mechanoreceptors. Stimuli applied to teeth evoke
      various oral reflexes, which make smooth mastication possible via the periodontal
      mechanoreceptors. Recent morphological and physiological studies have revealed
      that Ruffini endings, categorized as low-threshold slowly adapting type II (SA
      II), are essential mechanoreceptors in the periodontal ligament. The periodontal
      Ruffini endings are ultrastructurally characterized by expanded axon terminals
      filled with a number of mitochondria and terminal or lamellar Schwann cells. The
      axon terminals of the periodontal Ruffini endings have finger-like projections,
      i.e. axonal spines, extending into the surrounding tissue to detect the
      deformation of collagen fibers. As histochemical marker enzymes for the
      periodontal Ruffini endings, the axon terminals and terminal Schwann cells are
      reactive for cytochrome oxidase activity and both acid phosphatase activity and
      non-specific cholinesterase activity, respectively. Many experimental studies
      also have revealed that periodontal Ruffini endings have high potential for
      neuroplasticity, confirmed by intense immunoreactivity for p75-NGFR and GAP-43.
      Mechanical stimuli due to tooth eruption and occlusion might be a prerequisite
      for the differentiation and maturation of the periodontal Ruffini endings.
      Further investigations are needed for clarifying the involvement of growth
      factors and the molecular mechanism of the development and regeneration processes
      of the Ruffini endings.

PMID- 9617079
TI  - Sulfadoxine-pyrimethamine embryopathy in Wistar rats.
AB  - Pregnant Wistar rats received a therapeutic dose (0.72 mg/kg body weight) of
      intramuscular sulfadoxine-pyrimethamine on days 5, 12, and 19 of gestation. The
      treated animals showed elevated neutrophilic lobe average and increased urinary
      excretion of formiminoglutamic acid (FIGLU) as compared with controls (p <
      0.001), confirming folic acid deficiency due to sulfadoxine-pyrimethamine
      treatment. Complete embryo resorption occurred in the treatment group, while the
      control animals littered normally. These findings imply that sulfadoxine
      pyrimethamine should be used with utmost caution in early pregnancy as this
      regimen can lead to folic acid deficiency and consequent pregnancy wastage.

PMID- 9617080
TI  - Branches of the vagus nerve destined for the heart and the adjoining great
      vessels in the house shrew, Suncus murinus, with reference to the terminology of
      the vagal cardiac branches.
AB  - In order to help to organize the understanding of the bewildering complexities of
      the innervation of the mammalian heart by the vagus nerve and to clear up of
      confusions as regards the vagus cardiac branches, we scrutinized these branches
      in the adult house shrew, Suncus murinus, under a stereomicroscope. A number of
      branches were given off from the vagus nerve not only to the heart, but also to
      the adjoining great vessels, both outflowing and inflowing. When compared from
      the developmental viewpoint, the basic conformations of these branches on two
      sides were found not to differ from each other, but rather presented a
      symmetrical configuration, the feature which has been ascertained also in
      mammalian embryos. Relying on developmental criteria, we classified them into the
      arterial porta-related and the venous porta-related groups, formulating a new
      terminology by naming them on the basis of their destination. This version of
      terminology allowed us to define the vagus cardiac branches of the house shrew
      more accurately than the current terminology (e.g., Nomina Anatomica), and seems
      to provide us a clue for clearing up confusions concerning the terminology of the
      vagus cardiac branches in mammals.

PMID- 9617081
TI  - Frequency and classification of bony projections on the lower border of superior
      orbital fissure.
AB  - At the lower border of superior orbital fissure, at the junction of broad medial
      and narrow lateral portions of the greater wing of sphenoid bone, a bony
      projection (lateral rectus spine) occurs onto which the lateral rectus muscle and
      common tendinous ring attach. Such a bony projection has a special clinical
      significance not only because of its relationship with the contents of superior
      orbital fissure, but also because it is an attachment point for dura mater. In
      this study 286 males and 181 females, a total of 467 Anatolian dry skulls in
      which all the orbits were intact were examined. The bony projections mentioned
      above were classified according to their shapes. The ones most observed were the
      tubercle and spine forms which were 30.62% and 23.23% respectively. Of the 467
      dry skulls 156 (16.70%) had no bony projection on the lower border of superior
      orbital fissure.

PMID- 9617082
TI  - [Case report of the right-sided aortic arch (N-type): new classification based on
      macroscopic observations].
AB  - We report on a case with unusual origin of the left subclavian artery, so-called
      N-type found in a 62-year-old Japanese male in 1995. We took the opportunity in
      proposing for a new classification based on macroscopic observations. In the
      present observation, the following arteries branched off from the aortic arch in
      the order of the left common carotid, the right common carotid, the right
      subclavian and the left subclavian arteries. There was an aortic diverticum
      between the left subclavian artery and the dissending aorta. The left subclavian
      artery passed between the esophagus and the thoracic vertebrae. The arterial
      ligament connected the left pulmonary artery with the aortic diverticulum of the
      left subclavian artery. According to our observations, the arch of the aorta,
      descending aorta, aortic diverticulum of the left subclavian artery, arterial
      ligament and pulmonary artery joined to foam an incomplete vascular ring around
      the trachea and esophagus. This case can be classified into the N-type according
      to classifications by Adachi (1928), Williams (1932, 1935) and Nakagawa (1939).
      This may be the 22nd report in Japan regarding this kind of combined variations.
      Our classification also includes those by Takemura (1990) and Edwards (1964). An
      explanation of the new classification is described below and is also shown in
      Fig. 3. Abbreviations for classification types have been arranged in the order of
      the relation to the esophagus, the mirror-image subtyping of the Takemura's
      classification and the location of the arterial ligament. For example, type Na1
      (present case) represents the left subclavian artery passing behind the
      esophagus, mirror-image to the Takemura's G-type, and left arterial ligament.

PMID- 9617083
TI  - Duplication of the inferior vena cava: two case reports.
AB  - We encountered two cases of duplication of the inferior vena cava (IVC) in the
      Japanese cadavers of a 91-year-old man and a 71-year-old woman. Both of the
      anomalies were classified as Type BC and as Type I according to the systems of
      Chuang et al. (1974) and of Sarma (1966), respectively. In one case the right IVC
      was twice the diameter of the left IVC, and in the other it was five times as
      large. We discuss the clinical importance and the development of duplication of
      the IVC.

PMID- 9617084
TI  - E.F. Codd's classic article on database design.

PMID- 9617085
TI  - Self-treatment for obsessive compulsive disorder using a manual and a
      computerized telephone interview: a U.S.-U.K. study.
AB  - Bt steps is a patient-centered behavioral therapy program that uses a manual and
      a computer-driven interactive voice response system to assess and treat obsessive
      compulsive disorder. This nine-step program contains a self-assessment module and
      a self-treatment module that provides teaching on exposure and ritual prevention.
      The patient reads about the steps in a manual and then uses a touch-tone
      telephone to contact the program, in which a recorded voice conducts the
      interview. Of 40 patients in an open 12-week trial in the United States and
      London, 35 completed the self-assessment module, and 17 completed at least two
      sessions of exposure and ritual prevention. The system produced statistically
      significant improvements on measures of obsessive compulsive disorder.

PMID- 9617086
TI  - An intranet-based information system for nurses.
AB  - Nurses require extensive information and it must be up to date. At large highly
      specialized hospitals paper-based communication is not sufficient. This article
      describes the design and implementation of an intranet-based nursing information
      system for a major university hospital in Germany. The organizational
      infrastructure and the technical concept are discussed. The intensive use of the
      system during the first year of operation indicates an urgent need for
      computerized nursing information and suggests that intranet technology can meet
      this need.

PMID- 9617087
TI  - A relational model of data for large shared data banks. 1970.

PMID- 9617088
TI  - Conversion of a machine-dependent expert system into a web-based training tool.

PMID- 9617089
TI  - Computer-based training for "do-it-yourself" surgery: a case of attempted
      autoappendectomy.

PMID- 9617090
TI  - Musculoskeletal disease.

PMID- 9617091
TI  - Importance of the early diagnosis of hip pain: new approaches to hip preservation
      in osteonecrosis.

PMID- 9617092
TI  - Total joint replacement: a cost-effective procedure for the 1990s.
AB  - Total hip and knee replacement have been shown to be beneficial procedures not
      only by traditional clinical studies but by modern outcome measures as well. The
      cost-effectiveness of total joint arthroplasty compares favorably with non
      surgical treatments for patients with advanced arthritis of the hip and knee.
      While cooperation is necessary among all participants in the health care system
      to provide total joint replacement in a cost-efficient manner, dramatically short
      lengths of hospitalization and limitation of surgical implant selection are
      unlikely to provide any real cost savings. Total hip and knee replacement as
      currently performed will continue to offer cost-effective relief to patients with
      advanced arthritis of their major weight-bearing joints.

PMID- 9617093
TI  - The scope of musculoskeletal disease into the next millennium.

PMID- 9617094
TI  - Osteoporosis update.
AB  - Osteoporosis is a potentially devastating disease affecting millions of Americans
      with more than 1.5 million fractures annually at a cost that is projected to be
      more than 60 billion dollars by the year 2020. Heightened patient awareness and
      education regarding risk factors, especially of behavioral and nutritional
      factors, should help in prevention particularly when directed to the young. The
      availability of precise measurements of BMD now facilitates the assessment of
      patients, the need for therapeutic intervention, and assessment of the response
      to therapy. The increasing number of approved, safe and effective therapeutic
      agents and the continuing intense research efforts bode well for improved
      skeletal health for women of all ages.

PMID- 9617095
TI  - Diagnosis and treatment of spinal stenosis.

PMID- 9617096
TI  - Corneal arcus senilis and dyslipidemia.

PMID- 9617097
TI  - Health care quality improvement in Rhode Island: a methodology (Part 2).

PMID- 9617098
TI  - Advances in breast cancer genetics.

PMID- 9617100
TI  - Proposed goals for cancer prevention.

PMID- 9617099
TI  - Prevalence of arthritis in Rhode Island, 1996.

PMID- 9617101
TI  - [Rash and aggressive treatment].

PMID- 9617102
TI  - [Medical interactions with antidepressives. Benefits of the specific serotonin
      reuptake inhibitor citalopram].

PMID- 9617103
TI  - [Acne. Current aspects of pathogenesis].

PMID- 9617104
TI  - [Therapeutic possibilities for acne vulgaris].

PMID- 9617105
TI  - [Results of cervico-mediastinal lymphadenectomy using microsurgery technique in
      the treatment of occult metastases of papillary and medullary carcinoma of the
      thyroid gland].

PMID- 9617106
TI  - [Kidney-pancreas transplantation. Clinical results in 23 consecutive patients].
AB  - Immunosuppressive approaches to combined kidney-pancreas tx include quadruple
      therapy with either antilymphocyte globulin (ATG) or OKT3 for a short period (7
      14 days) immediately after transplantation. Maintenance therapy with prednisone,
      azathioprine and cyclosporin is then used to ensure the long-term survival of the
      graft. This study reports 23 cases of combined kidney-pancreas tx under ATG
      induction (n = 7) and OKT3 induction (n = 16). Both groups had maintenance
      therapy with azathioprine, prednisone and cyclosporin. The follow-up was 12
      months. Graft loss was 3 out of 7 vs 1 out of 16 (p < 0.05) for the kidney and 3
      out of 7 vs 3 out of 16 for the pancreas in ATG treated vs OKT3 treated patients
      respectively. There were two deaths in the ATG group and one in the OKT3 group;
      two patients died with functioning graft, one in each group. The one year
      actuarial survival was 87% for graft and patient, 83% for kidney and 77% for
      pancreas. Combined kidney-pancreas tx with ATG or OKT3 have a similar outcome.
      OKT3 allows a longer period before the onset of rejection. There is a trend in
      survivals which suggests a better survival in OKT3 treated recipients. Infections
      and other complications were similar in ATG and OKT3 patients.

PMID- 9617107
TI  - [Stenosis complications in digestive surgery: a histomorphological contribution.
      Comparison of mechanical and manual sutures].
AB  - BACKGROUND: Surgeons variously estimate usage of mechanical staplers in digestive
      surgery especially about the increase of the incidence of late complications like
      stricture (as some authors refer). We report a histomorphological aid to the
      comparison of staplers and hand-sewn sutures. Our aim was to observe at long term
      the healing process in the sutured tissue in the canine gastro-enteric tract.
      METHODS: We describe three histological pieces: one manual suture in a dog which
      was euthanatized and necropsied 5 months after operation and two mechanical
      sutures performed in two different dogs: one died because of a gastric torsion 18
      months after the operation while the other was euthanatized 5 months after the
      operation. The histomorphological study has been carried out with a peculiar
      cutting (Exact) and including method which lets the staples in situ. RESULTS AND
      CONCLUSIONS: Compared analysis showed that cicatrization goes on better in
      stapled than in hand sutured tissue.

PMID- 9617108
TI  - [Total gastrectomy and quality of life].
AB  - We have evaluated quality of life after surgery in 24 patients (9 males and 15
      females mean age 64.23 years, range 47-83 years) who underwent total gastrectomy
      for cancer (23 carcinomas and 1 lymphoma) in the last three years at the
      Department of Clinical Surgery, University of Siena. Intestinal continuity was re
      established with Y jejunal loup according to Roux. All patients were studied
      prospectively: after the operation every six months they were interviewed using
      Korenaga's questionnaire. Group performance status scale was used to determine
      the level of activity of each patients. Comparing symptoms of patients after six
      months and 18 months there was a significant difference (p = 0.005) in terms of
      number of meals throughout the day, food tolerance and abdominal pain.
      Postoperative performance status revealed a complete recovery in 11 of 24
      patients (45.8%) after 18 months. According to our experience patients who have
      undergone total gastrectomy enjoy a good quality of life and most of them return
      to the preoperative lifestyle in 18 months.

PMID- 9617109
TI  - [Gastrointestinal hemorrhage].
AB  - Acute digestive system haemorrhage is a recurrent cause of hospitalization. As to
      the upper segment of the digestive system, ulcerous peptic disease is often the
      cause of this pathology, above all in Western Countries. As to the lower segment,
      colic diverticula and angiodysplasy represent the most common cause. Bleeding
      usually clears up spontaneously or with hemodynamic pharmacological help. In some
      cases, the situation does not improve because of bleeding persistence, so more
      complex diagnostic and therapeutic techniques are necessary. Instrumental
      diagnostics is based on endoscopy (once with flexible optical fibre instruments,
      now with videoendoscopy) whose diagnostic effectiveness is inversely proportional
      to the latency since the haemorrhagic occurrence. Success is evident in 90-95% of
      the cases within the first twelve hours. Mesenteric angiography and scintigraphy
      with marked erythrocytes can solve difficult diagnosis and topographic location
      on some serious occasions. In every case the risk of complication and death is
      closely related to the haemorrhagic consistency, the flow of the bleeding, the
      basic disease, the age and the presence of chronic diseases. The authors examine
      a personal survey taken from the hospitalization in their own ward during a
      period of a year.

PMID- 9617110
TI  - [Videolaparoscopic treatment of biliary lithiasis. Evolution of our experience].
AB  - Videolaparoscopic cholecystectomy is considered the treatment of choice for
      simple cholelithiasis. Now many surgeons consider the laparscopic procedure
      usable also in the complicated biliary lithiasis like acute cholecystitis and
      choledocholithiasis. The authors report their recent experience of the
      laparoscopic treatment of biliary lithiasis, regarding 221 non-selected patients
      (69% symptomatic cholelithiasis, 20% chronic cholecystitis, 4.5% acute
      cholecystitis, 4.5% coledocolithiasis, 2% hydrops). The diagnostic-therapeutic
      protocol and the results are described and compared with the beginning of their
      experience, when they treated only symptomatic gallbladder stone disease, and
      with the reports of the literature. The authors concluded that the laparoscopic
      procedure is a good chance for the surgeon in the treatment of all cases of
      benign biliary disease. But, in particular for patients with choledocholithiasis,
      he has be able to know all the diagnostic and therapeutic possibilities, to
      choose the best in every single case.

PMID- 9617111
TI  - [Varicocele. Ligation of the internal spermatic vein using laparoscopic
      approach].
AB  - It is now unquestionable that varicocele represents one of the main causes of
      male infertility, and thus requires appropriate surgical treatment. Inguinal and
      retroperitoneal methods have for some time been the most widely used. However, a
      significant postoperative morbidity and relatively long convalescence have
      prompted the search for alternative surgical techniques, such as percutaneous
      sclero-embolisation and microsurgery. Laparoscopic treatment of varicocele is a
      relatively recent surgical technique. The first studies by Sanchez de Badajoz
      date back to 1988 and to date a relatively small number of cases have been
      reported. The authors analyse the results in 54 patients treated over a period of
      two and a half years; 13 cases also presented inguinal hernia pathology which was
      treated during the same operation by applying a polypropylene graft again using a
      laparoscopic approach; the latter method has been routinely applied since 1992 in
      over 1000 cases with excellent results. The internal spermatic artery was always
      identified and preserved. No peri- or postoperative complications were observed.
      A follow-up was performed at 10 months after surgery and showed results which
      although referred to a relatively small series, were certainly better than those
      reported in the literature using traditional surgical techniques; in addition,
      this method also reveals interesting possibilities for the treatment of
      associated pathologies during the same operation, with obvious advantages in
      terms of costs and patient compliance.

PMID- 9617112
TI  - [Surgical treatment of recurrent inguinal hernia using prosthetic materials].
AB  - The authors affirm that plastic surgery using graft materials is a feasible
      technique also in case of recurrent inguinal hernia. They follow with interest
      the evolution of laparoscopic techniques which are still the cause of some
      perplexity. The paper reports a series of nine recurrent inguinal hernias out of
      447 inguinal hernias operated during the period May 1994-May 1996.

PMID- 9617113
TI  - [Adrenal carcinoma. Clinical and anatomopathological prognostic factors].
AB  - We performed on 9 patients with adrenal cortical carcinoma a retrospective study
      during 1967-1995 to evaluate the most important prognostic factors. Four patients
      were males and five females (mean age: 40.3 years). Five patients had endocrine
      symptoms (55%) and four had "non-functioning" tumors (45%). The tumor involved
      the left adrenal gland in 5 cases and the right in 4. The mean diameter of the
      neoplasm was 9.5 cm, with a mean weight of 411 g. The average duration of
      symptoms before diagnosis was 7.3 months. One patient had invasion of the
      inferior vena cava with liver metastases. Eight patients underwent curative
      surgery, the median survival time was 13.7 months, only 1 patient is alive after
      18 months from surgical resection. We concluded that adrenal carcinomas have poor
      prognosis; staging and grading of the neoplasm, and age of the patient at
      diagnosis are predictors of survival.

PMID- 9617114
TI  - [Long-term results of radical lumbar ganglionectomy. Our experience].
AB  - We present our experience of 15 patients operated on by lumbar sympathectomies
      between 1987-1993, to confirm the effective and permanent efficacy of
      sympathectomy in peripheral vascular disease of the lower limbs. The patients, 9
      men and 6 women (age 58-86) presented with rest pain (12), and minimal toe
      lesions (3). After an eco color-Doppler and angiography of the lower limbs, a
      radical operative sympathectomy (L2-L5) was performed in all patients. Associated
      diseases were: ischemic cardiopathy (61.7%), renal failure (25%), diabetic
      disease (61.7%), carotid stenosis (25%), abdominal aortic aneurysm (12%). In four
      patients, was performed during the same surgical time, 2 abdominal aortic
      aneurysm repairs, and 2 aorto-bifemoral bypasses. No patients died, operative
      morbidity was 12.5% (2 cases). The clinical and instrumental follow-up performed
      on 6 patients (38.3%) after 3 years, demonstrated in all cases the regression of
      the rest pain (12 patients) and the healing of the toe lesions (3 diabetic
      patients). Our results confirm the efficacy of sympathectomy especially when
      performed in young patients. The small number of diabetic patients in our study
      made statistical evaluation difficult, but it is generally considered that the
      results are worse in diabetic patients, because the microvascular lesions in
      these patients reduce peripheral vasodilatation.

PMID- 9617115
TI  - [Long-term central venous access. Our experience].
AB  - Prolonged venous access devices (PVAD) represent a useful tool for many patients
      with chronic diseases. In the last 3 years 50 PVAD have been placed. Polyurethane
      catheters with a subcutaneous tunnel > 6 cm, have been used. There were no
      complications related to catheter insertion. The average life of PVAD was 95 days
      (range 7-425).

PMID- 9617116
TI  - [Free radial forearm flap and myocutaneous flaps in oncological reconstructive
      surgery of the oral cavity, Comparison of functional results].
AB  - In modern multi-disciplinary cancer treatment, rehabilitation and functional
      results represent utmost intent in reconstructive surgery of the oral cavity.
      Even in cases where the stage of disease is advanced) and the perspective of
      survival is limited, it is possible to achieve an acceptable quality of life. The
      authors report, in this study, the morpho-functional results and the morbidity
      observed in glossectomies in which the reconstruction was performed using three
      different methods. In a total of 264 reconstructive flaps of the head and neck
      regions, the authors considered three groups of 15 patients that had had
      reconstruction after the demolitive procedure. Respectively these groups were
      divided by the followed methods: free forearm flap, pectoralis major myocutaneous
      flap and nasolabial flap. The morbidity showed an extremely low rate of flap loss
      in all the groups, but "minor" complications, such as fistulas and leakages, were
      significantly more frequent in the myocutaneous flaps group. Functional
      evaluation for speech and deglutition showed good results in most patients.
      Extremely severe postoperative conditions as a permanent NG tube or
      incomprehensible speech had been observed in less than 15% of the cases.
      Particularly, the pectoralis major flap, showed its best functional performances
      in the total or subtotal glossectomies with a sacrifice of the muscles of the
      oral floor. The free forearm flap is reliable and safe with its low thickness and
      pliability, especially for partial glossectomies. The nasolabial flap was
      confirmed to be the first reconstructive choice for selected limited resections
      of the tongue and of the antero-lateral floor. With this experience it is
      possible, even in more complex free flaps, to reduce the time consumption and the
      complication rate. Free flaps do not substitute routinely myocutaneous and
      conventional flaps, but they represent the "ideal" reconstructive alternatives
      for specific and selected indications.

PMID- 9617117
TI  - The role of the contrast medium viscosity in the adequacy of operational
      cholangiography.
AB  - The viscosity of some routine hydrosoluble contrast media used in operational
      cholangiography (Bilignost and Verographin) was studied. The different viscosity
      of hepatic and vesical bile and of the contrast media was determined. This fact
      shows that the data of any direct cholangiography in accordance with the law of
      Hagen-Poiseuille is misinterpreted. As a result it may lead to a wrong surgical
      procedure, for example, sphincterotomy, and vice versa.

PMID- 9617118
TI  - [The cost as an additional variable in the choice among different techniques of
      postmastectomy breast reconstruction].
AB  - Breast reconstruction is an important step for patients after mastectomy. In our
      Department for immediate reconstruction, smooth or textured temporary tissue
      expanders filled with saline solution or permanent expandable implants (PEI) with
      silicon gel saline solution or soyabean oil are usually used. Only in a few
      selected cases reconstruction using autologous tissues are performed. Delayed
      reconstruction is performed using autologous tissues: Transversus Rectus
      Abdominis Myocutaneus Flap (TRAMF) or Latissimus Dorsi flap (LD). The choice
      between reconstruction with prostheses or muscular flaps depends on previous
      demolition, local skin condition, contralateral breast size and ptosis, body
      structure, medical problems, patients' wishes and expectation. Following the
      legislation defining the privatisation of Italian Health Care Structure and in
      particular the Decree of December 14, 1994, the need to accurately assess the
      costs incurred for surgical operations is very important. The aim of this study
      is to evaluate the clinical limits of each surgical technique and their cost in
      order to optimize the cost-benefit relationship.

PMID- 9617119
TI  - [Dilatation versus surgery in the treatment of cardial achalasia].
AB  - Both surgery and dilatation are useful for the treatment of cardial achalasia.
      The authors make a wide review of the literature with particular attention to
      reports comparing results of these procedures. This review evidences that surgery
      gives better results than dilatations (84.4% of good results with surgery against
      71.4% with repeated dilatations) and is certainly more stable over the years.
      Mini-invasive surgery points out even more strongly that surgery is nowadays to
      be preferred. Laparoscopy makes it possible to avoid postoperative pain, to
      discharge the patient in a couple of days and finally to eliminate surgical
      scars. Complications, even more frequent after surgery (5.5% against 2.1% of
      dilatation) are still acceptable in number and not heavy in quality.

PMID- 9617120
TI  - [Diverticulosis of the gallbladder. A case report and review of the literature].
AB  - We report a case of diffuse diverticulosis of the gallbladder in a 32 year old
      patient, who presents epigastric pains and decayed general conditions. With the
      suspicion of a primitive tumor of the gallbladder, we make a cholecystectomy and
      the intraoperative histological examination shows a "diffuse diverticulosis of
      the gallbladder wall"; it displays micro-stones inside diverticulums, too. The
      patient, after the surgical treatment, has no problem and he gets back to his
      normal weight. The literature shows the rarity of this disease; its
      etiopathogenesis is connected with congenital factors. In our opinion, the many
      terms used (cholecystitis glandularis proliferans, hypertrophic, adenomyomatosis)
      to define those conditions are not appropriate for our case but rather for the
      gallbladder's chronic inflammation characterized by the Rokitansky-Ashoff
      sinuses.

PMID- 9617121
TI  - [Intestinal perforation caused by a toothpick].
AB  - Intestinal injuries are pathologies frequently caused by toothpicks. In
      literature are reported serious damage to the cardiovascular system, lung and
      systemic fatal sepsis. In literature are also reported some deaths caused by
      delayed diagnosis. The authors report two cases of intestinal perforation by
      toothpick. Both patients had accidentally swallowed the toothpick. The clinical
      state was compatible with acute abdomen in a 59 year old psychopathic patient and
      acute appendicitis in a 27 year old patient. The aim of this paper is to
      emphasize the importance of a careful anamnesis for detecting the swallowing of a
      toothpick.

PMID- 9617123
TI  - Encapsulated intracerebral hematoma: a case report and review of the literature.
AB  - A case of encapsulated intracerebral hematoma is described in the light of the
      relevant literature. The etiopathogenesis, diagnostic problems and treatment of
      this rare entity are also discussed.

PMID- 9617122
TI  - [Rectal endometriosis. Apropos of a clinical case].
AB  - Regarding a case of rectal endometriosis, presenting with cyclic menstrual rectal
      bleeding, the authors discuss the clinical and treatment aspects of such a rare
      pathology. History was sufficient to indicate the diagnosis which was confirmed
      by the histological examination of the excised rectal tract. These observations
      underline the diagnostic difficulty; the surgical approach is the treatment of
      choice when medical treatment gives no success.

PMID- 9617124
TI  - [Cephalometric evaluation of patients with Turner syndrome. Authors' experience].
AB  - BACKGROUND AND METHODS: The cranio-facial morphology has been evaluated on the
      basis of cephalometric studies in nine patients with Turner's syndrome. The aim
      of this study is to identify the growth model and the typical malocclusions of
      this syndrome. This study has been completed with an evaluation of mesio-distal
      dimension of permanent teeth. RESULTS: According to the literature, the results
      show: a flattening of the basal skull; a cross-bite coming from a transversal
      dimension reduction of the upper maxilla. A Class II malocclusion was found in
      two patients. All the patients showed a mandibular retrusion associated to
      maxillary retrusion in eight cases. The growth direction was normal in all the
      patients. CONCLUSIONS: A reduction of the mesio-distal diameter in all of the
      permanent teeth, was also found. This last measure was evaluated using the study
      casts.

PMID- 9617125
TI  - [Postoperative follow-up after extraction of an impacted lower third molar].
AB  - BACKGROUND: On the basis of an anatomo-surgical classification adopted in our
      Department, that divides impacted lower third molars into (1) ectopic, (2)
      dystopic and (3) in the proper anatomical site, and the latter into Class A
      (complete bone impaction without pathology of the second molar), Class B (mucosal
      impaction with pathology of the second molar: Subclass B1, if the mucosa distal
      to the second molar is of a normal amount; Subclass B2, if the retromolar mucosa
      is plentiful), and Class C (mucosal semi-impaction), the authors carried out a
      comparative study on 20 patients who underwent extraction of both Class C lower
      third molars. METHODS: These operations were performed, in each patient, on one
      side raising an Archer's flap and on the other introducing a modification of the
      incision lines using Z-plasty for flap design. The patients were examined from
      the first postoperative hours up to the 7th day following a protocol aimed at
      monitoring the postoperative variables pain, edema, trismus, infection and
      healing time. RESULTS AND CONCLUSIONS: The preliminary results, analyzed by
      Student's "t"-test, are statistically significant (p < 0.05), and favour the
      hypothesis that the technical modification proposed for the flap, by permitting a
      better closure of the socket, involves a lesser incidence of postoperative
      complications and in any case a more comfortable postoperative course.

PMID- 9617126
TI  - [The Caldwell-Luc procedure in the management of maxillary sinusitis. Long-term
      results].
AB  - BACKGROUND: The surgical technique proposed by Caldwell and Luc more than a
      century ago has been applied in over a million cases to treat maxillary
      sinusitis. A critical re-evaluation of the method has been in progress for
      several years, in the light of the results that can be achieved with endoscopic
      functional surgery. METHODS: In a retrospective study, operations performed
      according to the Caldwell-Luc technique on 40 patients, mean age 45 years,
      between 1992 and 1996, were evaluated critically to determine the efficacy of
      this approach in treating maxillary sinusitis, with particular emphasis on the
      incidence of immediate or delayed complications. Initially, clinical and
      radiological data concerning each patient where considered with particular
      reference to the subjective and objective symptomatology, preoperative
      radiological diagnosis and etiology of the sinusitis. RESULTS: Having completed
      the analysis of the documentation available, some of the patients were recalled
      and subjected to an in-depth instrumental diagnosis through traditional and CT
      radiography. CONCLUSIONS: It was concluded that, in consideration of the marked
      incidence of complications, the Caldwell-Luc procedure may be defined as a non
      obligatory therapeutic option even in chronic maxillary sinusitis. The use of
      this surgical procedure is rational in cases of antral tumour, trauma, very
      serious mycotic or septic factors, or when a surgical approach to the pterigo
      maxillary fossa is necessary. In all other cases, the preferred treatment must
      now be endoscopy.

PMID- 9617127
TI  - [Arthrocentesis of the temporomandibular joint. Long-term results].
AB  - BACKGROUND: The studies carried out by Nitzan et al. (1991) to the assumption
      that the simple washing of the upper compartment of the temporo-mandibular joint,
      without introducing the arthroscope, associated to the application of a bite at
      night was sufficient to obtain a pain relieving effect and an improvement in the
      joint functionality in cases of internal derangement of TMJ. The purpose of this
      work is to assess the long-term results obtained in our department by using only
      the arthrocentesis without the association of other therapeutic procedures for
      evaluating the benefit brought by the simple washing of the upper compartment of
      the joint. METHODS: A sample of 10 patients subjected to arthrocentesis with an
      average follow-up of 23.8 months was examined. The evaluation of the patients was
      based on a clinical analysis and a series of instrumental tests including
      orthopanoramic X-rays, stratigraphies, RNM in some cases and an
      electrognatographic test. The parameters taken into consideration were maximum
      opening, articular noises, local pain in the articular region, the occurrence or
      not of headache. RESULTS AND CONCLUSIONS: In our opinion arthrocentesis is a
      method of simple application, well accepted by patients, leading to a clear
      improvement of symptoms, as far as pain relieving effect and functionality are
      concerned, thanks to the possibility to drain by washing the constituents of the
      inflammation and the mediators of pain; this method may be applied routinely, as
      therapeutic support, in those patients with clinical histories of condilo
      meniscal uncoordination and presenting limitations in the opening of the mouth
      and articular pains.

PMID- 9617128
TI  - [Hyperplastic gingival lesions in pregnancy. I. Epidemiology, pathology and
      clinical aspects].
AB  - The principal aspects of the hyperplastic pathology which frequently appears
      during pregnancy and its epidemiological and clinical aspects are discussed. The
      existence of a particular kind of gingivitis, typical in pregnancy, not different
      from that appearing in not-pregnant women, let to hypothesize the existence of a
      relationship between the gingival lesion and the particular hormonal condition
      observed in pregnancy. Sometimes pregnancy gingivitis can show a tendency towards
      localized hyperplasia, this condition is defined pregnancy granuloma. Clinically
      a mass of variable size is observed; generally it appears in the 2 degrees-3
      degrees month of pregnancy, with a tendency to bleeding and a possible
      interference with mastication. From a histological point of view, the pregnancy
      granuloma presents an inflammatory component characterized by lynphocytes,
      plasmacells and neutrophiles, an abundant vascular component with newly formed
      capillars and a great proliferation of fibroblasts. The differential diagnosis of
      pregnancy granuloma must be done with some forms of gingival hyperplasia, with
      pyogenic granuloma and with fibrous epulis (or hyperplasia). As to therapy, it is
      better to perform the surgical removal after delivery, considering that sometimes
      the lesions can spontaneously disappear. These lesions can reappear in a
      subsequent pregnancy.

PMID- 9617129
TI  - [Panoramic radiography using an intraoral tube. Method, anatomy, radiography and
      dosimetry].
AB  - BACKGROUND: There are two techniques giving a panoramic view of the dental arch:
      orthopantomography and intraoral tube panoramic radiography. The last one is not
      very well known because images, with a characteristic and variable deformity if
      compared with orthopantomography are not useful for routinary use in dentistry.
      The poor radiographic and pathologic anatomy knowledge of intraoral tube
      panoramic radiography, and the slight improvements brought to the method
      particularly in order to reduce the dose, partly depend on the scant attention
      given to the method by investigators, and partly on the dyshomogeneous anatomic
      sites enlargement and overlapping with consequent deformity of all of them. With
      intraoral tube panoramic radiography, X-ray exposition is emitted using a
      miniaturized cylindrical source placed inside the oral cavity and the
      radiographic film is in contact with the skin of the face. Based on the
      orientation of the collimator and the inclination of the tube major axis in the
      oral cavity, a central technique (exposition of either superior or inferior
      dental arch) and a lateral technique (simultaneous exposition of the two
      hemiarches of the same side) are recognized. The aim of this study is to give a
      significative contribution to maxillo-facial characteristic appearance and
      dosimetry knowledge in intraoral tube panoramic radiography. METHODS: It consists
      of: a) a "laboratory" part concerning the evaluation of the enlargement,
      deformation and visibility of different structures, obtained by positioning about
      fifty different markers in different maxillary and mandibular anatomic sites, and
      b) an in vivo dosimetry part obtained with intraoral and extraoral
      termoluminiscent dosimeters. An original dispositive allowed the right
      positioning of the film and its adherence to the screen. Deformity
      characteristics are analitically described and discussed in relation with the
      different sites. RESULTS AND CONCLUSIONS: The use of intensifying screens allowed
      a good reduction of dose, (mean absorbed doses ranging from 25 microGy in the
      intraoral sites to 1936 microGy in the extraoral sites) without reducing the
      image quality thanks to the device performed "ad hoc".

PMID- 9617130
TI  - [Topical cyclosporine in the treatment of oral pemphigus].
AB  - BACKGROUND: Pemphigus vulgaris presents the typical blistering lesions at the
      level of oral mucosa in nearly all patients. The main drugs used in the treatment
      of the disease are steroids and immunosuppressive agents. Among the latter,
      cyclosporine A plays a pivotal role. METHODS: In this study the effects of
      topical cyclosporine have been evaluated in 12 patients (4 males and 8 females,
      mean age 65 years) suffering from oral pemphigus for at least 4 years non
      responsive to the previous treatments. Five ml of oral suspension (500 mg) were
      divided into three times a day; cyclosporine had to be kept in the oral cavity
      for 15 mins and no food nor drinks were allowed for 30 mins before and after the
      oral wash. The treatment lasted for 2 months. RESULTS: At the end of the study a
      significant beneficial effect on erythema, oral lesions and pain was noticed. No
      side effects have been reported and the monitoring of full blood count, of renal
      and hepatic function and of blood pressure has not shown any variation from the
      baseline. Serum cyclosporine level has always been undetectable. CONCLUSIONS:
      These encouraging results in the treatment of oral pemphigus need to be confirmed
      in controlled studies.

PMID- 9617131
TI  - [The role of soft tissues in the planning of bimaxillary orthognathic surgery.
      Review of the literature and two clinical cases].
AB  - The authors have investigated the clinical role of the soft tissues and of their
      influence in the planning phase of the orthognathic surgery, with the purpose to
      emphasize their capital influence in the face armony. Most of the patients really
      ask for an aesthetic result, that is in a tight relation with the correct
      prediction of the morphological changes of the soft tissues. The aesthetics
      excite nowadays the research, especially in all the surgical fields, and so the
      orthognatic surgery is more than ever from the soft tissues influenced.
      Subsequently the authors have investigated the principal indications to the
      bimaxillary surgery and have suggested a personal diagnostic-therapeutic protocol
      for a correct and opportune evaluation of the soft tissues relations. Finally the
      authors have described the whole prediction phase and have shown as the maxillary
      bones influence the whole facial skelett, and as frequently the chin correction
      and the rhinoplasty are necessary for a better result in the time.

PMID- 9617132
TI  - [Secondary oro-mandibular reconstruction using revascularized bone flaps].
AB  - BACKGROUND: Oro-mandibular reconstruction using vascularized bone-containing free
      flaps can be accomplished with flap survival rates in the range of 95%. Primary
      reconstruction offers the best opportunity to achieve the optimal aesthetic and
      functional results. Patients presenting for secondary oro-mandibular
      reconstruction have a unique set of problems; these include the presence of soft
      tissue contracture displacing the mandibular segments in malposition and soft
      tissue deficiencies, that makes surgical correction more difficult and
      potentially more hazardous. Vascularized bone-containing free-flaps are indicated
      in secondary oro-mandibular reconstruction where both hard and soft tissues
      replacement is needed or when the recipient bed is unfavourable due to previous
      surgery and/or radiation. METHODS: Authors presents personal experience in ten
      cases of secondary oro-mandibular reconstruction treated at Maxillofacial
      Department of Parma from September 1995 to September 1996 with secondary oro
      mandibular reconstruction using bone containing free flaps. Two different donor
      sites were used to harvest bone-containing free flaps: iliac crest in 2 cases and
      fibula in the others. In 4 cases the flap was only osseous while in the other 6
      cases it was osteocutaneous. RESULTS: All flaps were transplanted successfully;
      in 1 case necrosis of the skin component of the flap was observed. CONCLUSIONS:
      The introduction of vascularized bone containing free flaps transferred from
      distant sites by microvascular techniques has changed mandibular reconstruction.
      Vascularized bone transferred into tissue beds compromised by salivary
      contamination and previous irradiation and the rational use of the soft tissutal
      components of the flap permit also the restoration of articulation, deglutition
      and mastication with quality of life better than non-vascularized alternatives.

PMID- 9617133
TI  - [Sinusoscopy in stomatology. Review of a 5-year clinical experience].
AB  - BACKGROUND: Investigative sinus endoscopy for purely diagnostic purposes has
      become an important therapeutic tool for disorders of the paranasal system thanks
      to the enormous technological developments of the last twenty years. METHODS: In
      a retrospective study, sinus endoscopies carried out between 1990 and 1994 on 57
      patients, mean age 43 years, were subjected to critical re-evaluation, with the
      aim of evaluating the efficacy of endoscopic treatment. In the first phase, the
      documentation available for each patient was examined; it included clinical data,
      preoperative traditional and CT radiographs, rhinoscopic and sinus endoscopic
      findings. Once the analysis of the available documentation had been completed the
      patients were recalled and subjected to clinical and radiological evaluation.
      Radiographic examination was carried out by traditional radiography. RESULTS: CT
      scanning was only performed for those patients in whom the clinical findings
      indicated a possible relapse. Immediate and delayed complications occurring after
      the endoscopic sinus surgery were taken into consideration. CONCLUSIONS: In
      conclusion, sinus endoscopy is a fundamental instrumental investigation in the
      diagnosis of rhinosinusopathies. It can no longer be considered as only a
      diagnostic investigation able to provide clear visual images, it also allows
      specimens to be taken for bacteriological, micological, cytological and
      histological analysis. Furthermore, endoscopic surgery can treat pathologies for
      which, until a few years ago, operations were necessary which respected the
      physiology of the paranasal system to a much lesser extent (Denker-Caldwell-Luc).

PMID- 9617134
TI  - [Actinomycosis of the tongue. Report of two cases and review of the literature].
AB  - Actinomycosis of the tongue is a rare form of infection whose initial clinical
      manifestation is a submucosal swelling that may mimic both benign and malignant
      neoplasias. Two cases are, presented and their clinical features and diagnostic
      criteria are discussed in the light of twelve cases drawn from the literature.
      Infection in the tongue is rare, though perhaps underestimated. It is generally
      located on the anterior two thirds laterally to the median sulcus, and presents
      as a moderately painful nodule set deep in the extrinsic and intrinsic muscles
      and poorly mobile on the adjacent planes. In a few weeks the lesion increases in
      size and painfulness with consequent loss of function in the absence of diagnosis
      and appropriate antibiotic management. Both our patients, in fact, presented with
      deep lesions and no apparent involvement of the mucosa, and were investigated by
      means of fine-needle aspiration biopsy (FNAB). The aspirated material was used to
      prepare both routine smears and cell blocks embedded in paraffin. The
      pathological material provided by this combination of methods proved
      quantitatively and qualitatively sufficient for the definitive diagnosis of
      actinomycosis in both cases.

PMID- 9617135
TI  - [Periodontal guided tissue regeneration with a rubber dam: short term clinical
      study].
AB  - BACKGROUND: The guided regeneration of periodontal tissues demonstrated to
      represent a therapeutical technique with predictable results. It has been
      observed that different materials, used as regenerative membranes, offer very
      similar results. Unconventional materials too, like the rubber dam, seem to be
      useful in the guided tissues regeneration technique. The object of the present
      study has been to comparatively evaluate the effectiveness of Gore-Tex and rubber
      dam-made membranes in the therapy of intra-osseous periodontal defects. MATERIALS
      AND METHODS: Six patients with two similar intra-osseous defects, participated in
      the study; one defect has been treated using, during the surgical intervention, a
      Gore-Tex membrane, while the other has received, a fragment of sterile rubber dam
      membranes. The principal clinical parameters of the periodontal health (probing
      depth -PD- and attachment loss -AL-) has been evaluated in both the defects
      before and 6 months after the periodontal surgery. RESULTS AND CONCLUSIONS: The
      results have showed that there are not statistically significant differences (p >
      0.05) in the healing of the intra-osseous defects treated by rubber dam or Gore
      Tex. The conclusion is drawn that the rubber dam can represent a valid and cheap
      alternative to the materials traditionally used in the regenerative surgery of
      the periodontal tissues.

PMID- 9617136
TI  - [Factors contributing to an increase in DLco (steady state) after exercise in
      healthy men].
AB  - We studied factors contributing to an increase of DLco (steady state) from rest
      to exercise in 10 healthy men. DLco(ss), Dm, and Vc were measured under three
      different conditions, rest, constant load exercise (50 watts), and
      hyperventilation (equal to the tidal volume and respiratory rate of exercise).
      DLco(ss) increased significantly during exercise and hyperventilation compared
      with at rest. DLco(ss) also increased significantly during exercise, compared
      with hyperventilation. During constant load exercise (50 watts) increased Dm and
      Vc, caused by increased ventilation, together with increased of Vc caused by
      increased of pulmonary blood flow resulted in an increase in DLco(ss).

PMID- 9617137
TI  - [HRCT findings of pulmonary Mycobacterium avium complex: a comparison with
      tuberculosis].
AB  - Computed tomographic (CT) findings of 70 patients with Mycobacterium avium
      complex (MAC) disease were analyzed by two chest radiologists and compared with
      those of 37 patients with Mycobacterium tuberculosis infection. Common CT
      findings in patients with MAC, included bronchiectasis (97%), small nodules
      (89%), parenchymal distortion (60%), bronchial wall thickening (56%),
      consolidation (50%) and cavity formation (49%) and small nodules (86%),
      bronchiectasis (70%), consolidation (57%) and bronchial wall thickening (51%) in
      patients with Mycobacterium tuberculosis. Bronchiectasis and parenchymal
      distortion were significant in patients with MAC compared with Mycobacterium
      tuberculosis patients. Bronchiectasis involving the RUL, RML, lingula and LLL and
      small nodules involving the RML were often seen in patients with MAC. Both
      bronchiectasis and small nodules were commonly observed in multiple lobes in both
      types of patients. Cavities in MAC infection tended to be thin and smooth walled,
      and less commonly associated with consolidation. We conclude that CT findings of
      MAC infection were characterized by widely distributed bronchiectasis and small
      nodules and/or cavities with thin, smooth walls. These CT findings are one of the
      keys in differentiating MAC from Mycobacterium tuberculosis.

PMID- 9617138
TI  - [Clinical significance of serum neuron-specific enolase in non-small cell lung
      cancer].
AB  - The present study was a retrospective analysis of serum neuron-specific enolase
      (NSE) assayed in 302 patients with non-small cell lung cancer (NSCLC) before
      treatment. Serum NSE ranged from 0.6 to 183.0 ng/ml, with a mean value of 12.2
      ng/ml, and exceeded 10 ng/ml in 145 patients (48.0%). The mean levels and rate of
      NSE positivity in 177 patients whose tumors were categorized as small, medium and
      large (from the product of the maximum and perpendicular axis of the tumor on
      chest X-ray), were highest in the large group. There was no significant
      relationship between serum NSE and the response rate to anticancer chemotherapy.
      The survival period of the patients with elevated serum NSE (median, 5.7 months)
      was significantly shorter, than those with normal serum NSE levels (median, 12.1
      months). Serum NSE is of prognostic significance in a multivariate analysis (p <
      0.01), but not predictive of response to chemotherapy in NSCLC.

PMID- 9617139
TI  - [Usefulness of marking with colored collagen to localize small pulmonary nodules
      for thoracoscopic biopsy].
AB  - We examined the usefulness of marking with colored collagen to localize small
      pulmonary nodules (less than 10 mm in diameter) for thoracoscopy. Before using
      colored collagen, 2 of 6 lesions (33%) could be localized. It was possible to
      localize 14 of 15 lesions (93%) for thoracoscopy after marking with colored
      collagen, a percentage that is significantly higher than localization without
      such marking (P < 0.01). Thus, marking using colored collagen is useful to
      localize pulmonary nodules less than 10 mm in diameter for thoracoscopy.

PMID- 9617140
TI  - [Eosinophil count in induced sputum samples as a marker of airway inflammation
      and adequacy of corticosteroid inhalation treatment in asthmatic patients].
AB  - We tried to use eosinophil counts in induced sputum samples as a marker of airway
      inflammation, and as a guide for reducing inhaled corticosteroids in patients
      with well-controlled persistent asthma. The eosinophil count in induced sputum
      smears was defined as follows: Eos%; eosinophil percentage of 200-400 leukocytes
      in properly cell-separated fields, TEC; total eosinophil counts in the 5 most
      eosinophil-dense high power view fields (x 400). First, the eosinophil count in
      induced sputum samples was compared between 29 asthmatic subjects treated with
      inhaled corticosteroid and 15 age- and sex-matched healthy controls. Second,
      inhaled corticosteroid was reduced by 50% in 20 patients with green-zone asthma
      (morning PEF > 80% of patient's best PEF). PEF measurements were followed
      prospectively for 12 weeks thereafter. Once PEF decreased below 70% of their best
      PEF, subjects were considered as treatment "failures". Both Eos% and TEC were
      significantly higher than in the controls, even in well-controlled (morning PEF >
      80% of their best) asthmatic patients (p = 0.001, 0.03). The chance of treatment
      "failure" was significantly higher in those having more eosinophils (Eos% > 10%,
      TEC > 100) in their initial induced sputum sample (p = 0.03, 0.001). Airway
      inflammation still persists in many well-controlled chronic asthmatic patients,
      and induced sputum eosinophilia predicts an early decrease of PEF after reduction
      of inhaled corticosteroids.

PMID- 9617141
TI  - [Increase in pulmonary vascular permeability caused by increased adhesiveness of
      polymorphonuclear leukocytes and superoxide].
AB  - We report that mechanical stimulation of human neutrophils results in their
      accumulation in isolated rat lungs and in an increase in pulmonary vascular
      permeability. To determine whether reactive oxygen species were involved in this
      increase and, if so, whether it is mediate by xanthine oxidase metabolites, we
      assessed the effect of stimulated and unstimulated neutrophils, and of a
      superoxide scavenger, superoxide dismutase (SOD), and a xanthine oxidase
      inhibitor, allopurinol (ALLO) on pulmonary vascular permeability in isolated
      perfused lungs from Sprague-Dawley rats. Pulmonary vascular permeability in
      isolated rat lungs was assessed using a filtration coefficient determined by
      gravimetry. To quantify neutrophil accumulation in the lung, we measured
      myeloperoxydase (MPO). Neutrophils were stimulated by gentle agitation in a glass
      container for 10 s and Mac-1 was subsequently upregulated on the surface of the
      neutrophils. In lungs that received stimulated neutrophils, the pulmonary
      vascular filtration coefficient was about 5 times higher than in lungs that
      received unstimulated neutrophils. An increase in filtration coefficient was
      almost completely blocked by pretreatment with SOD or ALLO. However, the
      accumulation of stimulated neutrophils was not, or only partly, blocked by SOD or
      ALLO, respectively. We conclude that the increase in pulmonary vascular
      permeability caused by mechanically stimulated neutrophils was partly mediated by
      reactive oxygen species generated via the xanthine oxidase system.

PMID- 9617142
TI  - [Effects of bathing on lung mechanics in patients with severe COPD].
AB  - Although it is well known that the majority of patients with severe COPD complain
      of exacerbated dyspnea while taking a Japanese-style bath, the mechanism has not
      been elucidated. We therefore investigated changes in lung volume (LV) and SaO2
      in 16 seated patients with severe COPD, receiving treated with home oxygen
      therapy (HOT), and in 10 healthy subjects (C) immersed to the navel (N) and to
      the shoulder (S). We then subdivided the COPD patients into 2 groups, A and B.
      Group A was composed of patients taking less than 2 L oxygen/min, while group B
      was taking equal to or greater than 2 L oxygen/min. Expiratory reserve volume
      (ERV) decreased with statistical significance (p < 0.05) while inspiratory
      capacity (IC) substantially increased as immersion progressed. However, changes
      in LV were smaller, as obstructive ventilatory changes progressed. It also
      appeared that a significant O2 desaturation occurred in patients with COPD when
      movement was associated with taking a bath. The drop in SaO2 during bathing was
      significantly improved after patients received instructions concerning posture,
      slow movements, and pursed-lip breathing. These findings suggest that immersion,
      such as when taking a Japanese-style bath, 1) may change various LV to a lesser
      degree than in healthy subjects because of previously existent airway obstruction
      in COPD, 2) may aggravate arterial desaturation through further impairment of the
      VA/Q imbalance, 3) instructions for COPD patients could improve, their condition
      while bathing and, 4) the 6 minute walking distance (6 MD) might be important in
      predicting the severity of arterial desaturation while COPD patients are
      immersed.

PMID- 9617143
TI  - [Two cases of anti-neutrophil cytoplasmic antibody-negative generalized Wegener's
      granulomatosis with alveolar hemorrhage].
AB  - Anti-neutrophil cytoplasmic antibody (ANCA) is a distinct marker for Wegener's
      granulomatosis. We report two cases of ANCA-negative Wegener's granulomatosis. A
      70-year-old woman (case 1) and a 27-year-old woman (case 2), who had sinus
      symptoms and renal disorders, were admitted to our hospital with alveolar
      hemorrhage. Wegener's granulomatosis was diagnosed on biopsy of the nasal mucosa.
      Case 1 responded well to the combination therapy with cyclophosphamide and
      prednisolone, while case 2 responded well to pulse therapy with methyl
      prednisolone. These findings suggest that patients with ANCA-negative Wegener's
      granulomatosis may respond well to chemotherapy. This might lead to an improved
      prognosis in even severe cases, even though the prognosis of generalized
      Wegener's granulomatosis with alveolar hemorrhage is usually poor.

PMID- 9617144
TI  - [A case of lung abscess caused by Eikenella corrodens].
AB  - We report a case of lung abscess caused by Eikenella corrodens and reviewed the
      literature. A 51-year-old man was hospitalized because of an infiltrative shadow
      in the left upper lung on chest X-ray. The patient was intravenously given CEZ (2
      g/day) followed by CEZ (4 g/day) and AMK (200 mg/day). We nevertheless
      deteriorated and was subsequently treated with CTM (4 g/day) and LCM (6 g/day),
      and the shadow improved but remained. Only Eikenella corrodens was isolated from
      aspiration materials obtained from the resected lung. We examined the
      susceptibility of 60 strains of Eikenella corrodens to various antimicrobial
      against. The organisms were very susceptible to PCG, ABPC, PIPC, CTM, CTX and
      LMOX, but were all resistant to LCM, CLDM, GM and AMK.

PMID- 9617145
TI  - [Swyer-James syndrome with pneumothorax].
AB  - We report a case of Swyer-James syndrome with pneumothorax. A 20 year-old man was
      admitted to our hospital with dyspnea. Right pneumothorax was diagnosed by chest
      X-ray. He had a history of current pneumonia in childhood. After improvement of
      the pneumothorax, chest X-ray revealed hyperlucency of the right upper lung.
      Chest-CT revealed a low attenuation area and a cystic space in the right upper
      lobe. Xenon-133 clearance was delayed in ventilation scintigraphy. Bronchography
      showed cylindrical bronchiectasis in the proximal bronchi and poor filling of the
      peripheral bronchi in the right upper lobe. Pulmonary angiography showed a small
      right upper pulmonary artery. Swyer-James syndrome was diagnosed. The
      pneumothorax was probably caused by weakness of the cystic spaces.

PMID- 9617146
TI  - [A case of Bence-Jones protein-lambda positive multiple myeloma complicated by
      abnormal plasma cells in pleural effusion].
AB  - A 53-year-old woman was admitted to this institution with chest pain and dyspnea.
      Chest roentgenogram showed pleural effusion and multiple tumor shadows,
      bilaterally which represented extrapleural signs. Numerous atypical plasma cells
      were found in the pleural effusion. Bone marrow biopsy showed atypical plasma
      cells. Immunoelectrophoresis revealed monoclonal Bence-Jones protein-lambda in
      serum and urine. Myeloma was subsequently diagnosed and chemotherapy was started.
      Multiple myeloma is a plasmacytoma, and myeloma cells proliferate in the bone
      marrow. The incidence of myeloma associated with malignant pleural effusion is
      rare with only 33 cases previously reported in Japan, to the best of our
      knowledge.

PMID- 9617147
TI  - [Acute exacerbation of subacute interstitial pneumonia after thoracoscopic lung
      biopsy].
AB  - A 55-year-old woman was admitted to our hospital with progressive dyspnea that
      had begun one month before. Chest rentogenogram revealed groundglass appearance
      and reticular shadows bilaterally. Pulmonary function tests showed both decreased
      vital capacity and diffusing capacity. Bronchoalveolar lavage fluid had a high
      lymphocyte fraction with a low CD4+/CD8+ ratio. Thoracoscopic lung biopsy
      revealed thick, fibro-edematous interstitium and diffuse infiltration of
      lymphocytes. We also observed an intra-alveolar exudate with infiltration of
      histiocytes and lymphocytes. The clinical features and pathological findings were
      consistent with subacute interstitial pneumonia, which was the entity proposed by
      Kawabata and colleagues. The patient developed acute respiratory failure four
      days after lung biopsy and died despite steroid pulse therapy. Although subacute
      interstitial pneumonia has been reported to respond to steroid therapy, and to
      have a good prognosis, we believe that subacute interstitial pneumonia could
      fatally worsen when associated with lung biopsy, infection, or some other
      stimulus.

PMID- 9617148
TI  - [Lung abscess in a patient with Good's syndrome and pure red cell aplasia].
AB  - A 56-year-old man with pure red cell aplasia (PRCA), hypogammaglobulinemia and
      mediastinal tumor was admitted to our hospital with of dyspnea, high fever and
      general fatigue. Chest X-ray showed a large cavity with a niveau in the left
      lung. Biopsy of the mediastinal tumor revealed an epithelial cell-type thymoma.
      Lung abscess with Good's syndrome and PRCA was diagnosed. Antibiotics was
      administered, and percutaneous catheter drainage of the lung abscess was
      performed. He recovered and was discharged. Hypogammaglobulinemia in the case may
      have resulted from reduced production of gammaglobulin associated with a
      quantitative B-cell defect.

PMID- 9617149
TI  - [A case of intrapulmonary lymphangioma].
AB  - We report an extremely rare case of intrapulmonary lymphangioma. A 41-year-old
      woman was admitted to our hospital for complete medical evaluation of a pulmonary
      nodule on chest X-ray, which was found during an annual check-up. Chest
      radiograph showed a well-circumscribed spherical mass adjacent to the right
      border of the heart in the right lower lung field. Although a cystic tumor of the
      lung was suspected based on computed tomogram and magnetic resonance imaging
      findings, a histologic diagnosis could not be made on transbronchial biopsy. In
      addition, the nodule had increased in size compared with a chest X-ray taken 1
      year previously. Enucleation was performed. Histological examination revealed
      numerous cysts with thin walls lined by a single layer of cells in which
      immunoreactivity to von Willebrand factor was weakly positive. Intrapulmonary
      lymphangioma was subsequently diagnosed.

PMID- 9617150
TI  - [A case of pulmonary sarcoidosis with multiple cavitation and pneumothorax].
AB  - We describe a rare case of pulmonary sarcoidosis with multiple cavitation and
      pneumothorax. A 32-year-old woman was admitted to our hospital with a dry cough
      and an interstitial shadow with dense infiltrates in both upper lungs and
      cavitation in the right upper lung on chest roentgenogram and CT. Laboratory
      tests revealed an elevated level of serum lysozyme. BAL fluid demonstrated a high
      proportion of lymphocytes with an increased CD4/CD8 ratio, compatible with
      sarcoidosis. Transbronchial lung and skin biopsies showed evidence of
      noncaseating epithelioid-cell granuloma, and a diagnosis of sarcoidosis was made.
      Although pneumothorax appeared in the left lung on chest roentgenogram during
      clinical observation conservative treatment without corticosteroids or any other
      therapy for a follow-up period of 3 years resulted in improvement of her clinical
      condition and abnormal X-ray findings.

PMID- 9617151
TI  - [A case of PTH related protein-producing large cell carcinoma of the lung].
AB  - A 41-year old woman with lung cancer was admitted to our hospital with
      constipation, lumbago and paraplegia. Her serum calcium level was 13.9 mg/dl. She
      expired on the 33rd hospital day despite vigorous fluid and supportive therapy.
      An autopsy was performed 1 hour later. The cause of death was rupture of the
      sigmoid colon and panperitonitis. To evaluate the etiology underlying the
      symptomatic hypercalcemia in the autopsied lung, we measured serum and tumor
      tissue concentrations of PTH-related protein (PTHrP) by radioimmunoassay using a
      specific antibody against human PTHrP (1-34), and performed immunohistochemical
      staining by the peroxidase-anti-peroxidase method with the same PTHrP antiserum.
      Northern blot analysis was also performed to detect messenger RNA in cancer
      tissue. All of these tests were positive for PTHrP. To the best of our knowledge,
      this is the first reported autopsied case demonstrated to be a PTHrP-producing
      large cell lung cancer by molecular biological methods.

PMID- 9617152
TI  - [A case of pulmonary infiltration with eosinophilia caused by Ascaris suum].
AB  - A 46-year old man was admitted to our hospital with dry cough and diarrhea. His
      chest CT showed diffuse subpleural small nodular shadows. Eosinophilia and an
      increase of serum IgE were detected. Eosinophils were also increased in BALF. An
      antibody against Ascaris suum was positive in serum while other causes of
      eosinophilia (e. g., drugs, fungus, collagen disease) were absent. Ivermectin was
      administered and the diarrhea improved within 3 days. The abnormal chest shadows
      and dry cough disappeared 3 months later. Pulmonary infiltration with
      eosinophilia (PIE) syndrome caused by Ascaris suum was diagnosed because of the
      clinical course and serum examination results. Recently, zoonoses are increasing
      with the boom of oversea travel and "natural" foods. We report a case of PIE
      syndrome caused by Ascaris suum and describe the clinical features and the social
      significance including the origin of this disease.

PMID- 9617153
TI  - [A case of pulmonary arteriovenous fistula beneath the surface of the lung].
AB  - A 19-year-old woman complaining of exertional dyspnea was admitted to our
      hospital with an abnormal shadow on the left side of the chest. Laboratory
      examination revealed polycythemia and hypoxemia. Pulmonary angiogram demonstrated
      a pulmonary arteriovenous fistula beneath the surface of the left S10. Partial
      resection of the left S10 was performed. The wall of the arteriovenous fistula
      was flimsy and seemed to rupture easily. The sister of this patient also had a
      peripheral pulmonary arteriovenous fistula and suffered from repeating epistaxis.
      Rendu-Osler-Weber disease was diagnosed in both, and the sister underwent partial
      resection of the right S7, which contained the fistula. Their postoperative
      courses were uneventful. Hemothorax and hemoptysis are lethal complications of
      arteriovenous fistulae. In order to avoid the rupture of fistulae, surgical
      resection is the most reliable treatment. Pulmonary arteriovenous fistulae
      beneath the surface of the lung should be resected.

PMID- 9617154
TI  - [High-resolution CT-pathologic correlation of small adenocarcinoma of the lung].
AB  - High-resolution CT findings of 47 small pulmonary adenocarcinomas (20 mm or less
      in diameter) were correlated with the pathological classification of Noguchi et
      al. All seven tumors of Noguchi's type A showed homogeneous groundglass
      attenuation and no air densities except air bronchogram. Linear density radiating
      into surrounding lung parenchyma was not found in type A tumors. On the other
      hand, 38 of 40 tumors of types B, C, and D had some dense opacity domain, which
      increased in size in that order. Coarse indentation, which was not found in cases
      of type A and B tumors, was considered to be an important finding in
      differentiating cases in the good prognosis group (types A and B) from those in
      the poor prognosis group (types C and D).

PMID- 9617155
TI  - [Collaterals after flow alternation in pelvic arteries: precondition for pelvic
      reservoir therapy].
AB  - To determine the best flow alternation in the internal iliac arteries for
      regional chemotherapy using a reservoir to treat pelvic malignancies, collateral
      arteries that arose after arterial flow alternation were evaluated on follow-up
      pelvic angiographies. Follow-up angiographies were obtained in 11 patients with
      21 embolized arteries; six male and five female patients including three with
      urinary bladder cancer, two with prostate cancer, four with uterine cervical
      cancer and two with bone metastasis. The interval until follow-up angiography
      ranged from one to-28 months (mean 8.9 months). Three radiologists interpreted
      the angiographic results and evaluated collateral vessels. Among 21 embolized
      arteries, 19 were well occluded, while two were not blocked completely. The two
      arteries with incomplete embolization did not induce collaterals. Eight internal
      iliac arteries occluded at the proximal portion enhanced retrogradely via
      collaterals from the ipsilateral external iliac arteries. Collaterals between the
      bilateral internal iliac arteries were noted only in four of them. In conclusion,
      embolization at the proximal point of the internal iliac arteries usually induced
      collaterals from the ipsilateral external iliac arteries and did not always from
      collaterals between the bilateral internal iliac arteries, which were necessary
      for regional chemotherapy. This should be considered when pelvic malignancies are
      treated with reservoirs.

PMID- 9617156
TI  - [Diagnosis of intraductal spread of breast cancer by high-resolution MR imaging:
      correlation between MR imaging and pathohistological findings].
AB  - The main purpose of this study was to investigate pathohistological factors that
      affect the MR findings of intraductal spread (IDS) of breast cancer. The subjects
      of the present study were 42 breast cancer patients who were examined by MR
      imaging. Fat-suppressed high-resolution T1-weighted spin-echo images [350/13/1
      (TR/TE/excitations), 16-cm FOV, 5-mm section thickness, and 512 x 256 matrix]
      were obtained one minute after the intravenous administration of Gd-DTPA. In this
      protocol, contrast determination time was 1 min 48 sec. Of the 42 cases, IDS was
      found to be located more than 1 cm from the primary focus in 22 cases (52%).
      Rates of sensitivity, specificity and accuracy of MR imaging for the detection of
      IDS were 82%, 80%, and 81%, respectively. The probable cause of misdiagnosis was
      parenchymal enhancement due to severe fibrocystic disease and normal menstrual
      cycle. In 21 of 42 cases, the MR findings were precisely correlated with the
      pathohistologic findings of almost the same cross-section. The MR findings of IDS
      varied greatly with observation of linear, band-like, branch-like, plate-like and
      minute ring enhancements. These findings closely reflected the size, aggregation
      pattern, and distribution of intraductal lesions. In particular, minute ring
      enhancement was only observed in 4 comedo-type lesions. This pattern of
      enhancement is considered to reflect elevated intraductal cellular density with
      necrosis in the central region.

PMID- 9617157
TI  - [Enhanced MR imaging with a nonionic contrast gadolinium complex, Gadoteridol,
      for lumbar disc herniation].
AB  - The aim of this study was to evaluate the usefulness for lumbar disc herniation
      of enhanced imaging with a nonionic contrast gadolinium complex (Gadoteridol).
      Among 130 discs in 26 patients, 27 herniated discs were shown on MR sagittal
      imaging. They were classified into 4 types according to the enhancement pattern
      of the disc on MR sagittal imaging (Type Ia: nonenhancement, Type Ib: globular
      enhancement, Type II: strong enhancement, Type III: ring enhancement). The
      results were as follows: Type Ia: 3, Type Ib: 15, Type II: 7, Type III: 2. A
      total of herniated discs were enhanced with Gadoteridol. Surgery was performed in
      5 patients (Type Ib: 1, Type II: 4). The herniated disc of Type Ib extruded but
      did not rupture the posterior ligament, whereas the herniated discs of Type II
      extruded and ruptured the posterior ligament. Thus, the herniated discs were
      enhanced with the nonionic contrast agent Gadoteridol. If the disc herniates over
      the posterior ligament, it might be strongly enhanced. Therefore, enhanced MR
      imaging is thought to be useful to establish the diagnosis of lumbar disc
      herniation.

PMID- 9617158
TI  - [Radiotherapy in the treatment of brain metastasis from small cell lung
      carcinoma: study on appropriately controlled dose].
AB  - Fifty-two brain metastatic lesions occurring in 20 patients with small cell lung
      carcinoma (SCLC) were irradiated, and then the relationship between tumor size,
      dose and control was clinically and histopathologically studied. Lesions of 8 mm
      in diameter and those of 10 mm in diameter were determined to be controllable by
      irradiation at about 38 Gy and 42 Gy, respectively. According to size-dependent
      curative minimum doses, the lesions could be divided by the 10 Gy/ 5fr/wk method
      into controlled and non-controlled groups with the curve expressed as dose (Gy) =
      15.27 log10 [tumor volume (mm3)] +0.6. Based on these results, tumors of 2 mm and
      3 mm in diameter were estimated to be controllable at 14 and 20 Gy, respectively.
      Thus prophylactic cranial irradiation (PCI) in the treatment of SCLC was thought
      to be not always necessary if early treatment of small metastatic lesions,
      detected by Gd-DTPA-enhanced MRI could be achieved. The optimal interval between
      follow-up examinations was thought to be 1 month during the first two years after
      the diagnosis of SCLC, and then 3 months after that. In addition, the omission of
      PCI can save many patients who do not actually require PCI from suffering its
      adverse effects.

PMID- 9617159
TI  - [Gd-DTPA enhanced multi-shot echo-planar MRI: improvement of contrast between
      metastatic liver cancer and liver parenchyma].
AB  - In six patients with metastatic liver cancer, spin-echo multi-shot echo-planar MR
      imaging 8/2000/80/1 (shot/TR/TE/excitation) of the liver was performed before and
      30, 60, 90 and 120 sec after the intravenous injection of Gd-DTPA. Signal-to
      noise ratios (SNR) of the liver tumor and liver parenchyma were measured in each
      phase. The contrast-to-noise ratios (CNR) between the tumor and liver parenchyma
      were also calculated. While the SNR of the tumor did not change after the
      injection of Gd-DTPA, the SNR of the liver parenchyma decreased and the CNR
      between the tumor and liver parenchyma increased.

PMID- 9617161
TI  - [Modern intensive medicine and the end of life].

PMID- 9617160
TI  - [Three-dimensional CT angiography for cerebral aneurysm using a multi-angle
      reconstruction plan method].
AB  - The purpose of this study was to evaluate the clinical usefulness of three
      dimensional CT angiography (3D-CTA) for the diagnosis of cerebral aneurysm using
      a new reconstruction method called Multi-Angle Reconstruction Plan (MARP). The
      threshold values, region of interest and six angles of view were preset for the
      MARP method on the basis of our experience with cerebral 3D-CTA. Spiral CT
      angiography was performed in 27 patients with 29 aneurysms. The six images
      reconstructed with the MARP method were generated from the volumetric CT data.
      Two radiologists independently reviewed the six 3D-CT images for the presence of
      aneurysm. It took about five minutes to semiautomatically reconstruct the six 3D
      CT images with the MARP method. There were no discrepancies in the evaluation of
      the 3D-CT images. Twenty-six aneurysms of 24 patients were demonstrated on the
      six 3D-CT images. Three aneurysms in 3 patients were not depicted on the 3D-CT
      images by the MARP method. In them, the additional 3D-CT images which were
      generated after evaluating the 2D-CT images clearly showed the aneurysms. The
      MARP method is considered to be a useful three-dimensional reconstruction
      technique for the diagnosis of cerebral aneurysm.

PMID- 9617163
TI  - [Physicians need to know more about pain relieve].

PMID- 9617162
TI  - [Denmark's first research facility in palliative medicine. Organization and
      research strategy].
AB  - Denmark's first palliative medicine research unit is now being set up at
      Bispebjerg Hospital, with single-room and two double-room ward. The
      multidisciplinary team consists of doctors, a psychologist, nurses, a
      physiotherapist, an ergotherapist, a medical social worker, a priest and a
      dietician. An out-patient facility is also being established to enable patients
      to choose between hospitalisation out-patient treatment or home treatment by
      appropriate staff. Another aspect of palliative medicine is care of the patient's
      family members. The intervention offered at our facility is led by a
      psychologist, and consists primarily of counselling. With its limited clinical
      opacity, the department of palliative medicine is first and foremost a research
      and development facility. The first chair in palliative medicine in Denmark was
      conferred upon the department in 1998.

PMID- 9617164
TI  - [The dying patient--a challenge to health care personnel].
AB  - What are doctors and nurses experiences in their work with dying patients?
      Interviews with six nurses and four doctors from Norway, Sweden and Denmark were
      analysed using Grounded Theory as the qualitative method. A model is presented
      consisting of basic trust divided into two main categories--internal and external
      trust. Internal trust is characterised by confidence, competence and personal
      growth. External trust is based on communication, time for care, continuity in
      care and rituals. The two categories are dependent on each other, meaning that a
      good caring organisation can make it possible for even an insecure person to do
      their job. To work with dying patients gives an opportunity of personal growth.

PMID- 9617165
TI  - [Repair of cartilage defects].

PMID- 9617166
TI  - [Disk surgery--neurosurgery, orthopedic surgery or both?].
AB  - Bibliometric methods have been used to study the distribution of research
      literature on disc surgery between neurological and orthopaedic departments
      globally and within each of the Nordic countries. Worldwide, the total number of
      indexed papers was found to be almost twice as great for neurosurgical as for
      orthopedic institutions. Though figures for the Nordic countries were lower, they
      manifested the same trend, except those for Sweden where orthopaedic surgeons
      appear to do more research than neurosurgeons in this field. Moreover, it was
      found that a greater proportion of neurosurgeons than orthopaedic surgeons had
      published papers in journals outside their own field (29 vs 9 per cent
      respectively), and that 14 per cent of the neurosurgical reports had been
      published in orthopedic journals, but none of the orthopedic reports had been
      published in neurosurgical journals. Finally, scrutiny of the reference
      literature cited in randomly selected samples of papers from neurosurgical and
      orthopedic departments showed 22 per cent of the references in neurosurgical
      papers to be to orthopaedic journals or textbooks, but only 4 per cent of those
      in orthopedic papers to be to neurosurgical texts. The possible implications of
      these findings are discussed in the article, as are the methodological sources of
      error.

PMID- 9617167
TI  - [Pain analysis is vital in rheumatic diseases. Pain often causes much worry to
      patients].
AB  - The article consists of a synthesis of a rheumatic pain symposium held at the
      annual meeting of the Swedish Medical Association in 1996. Various aspects of
      pain in rheumatic diseases were discussed, such as physiological, neurohumoral
      and neurogenic mechanisms, sensory stimulation treatment, differentiation of
      mechanical and inflammatory pain, quality enhancement by improved co-operation
      between primary and tertiary care facilities, pharmacological treatment with
      (centrally and peripherally acting) opioids, selective cyclo-oxygenase
      inhibitors, and NMDA (N-methyl-D-aspartate) receptor antagonists. For patients
      with rheumatic disorders exacerbated by pain problems, as for other patients, a
      pain diagnosis is of fundamental importance. This can be achieved by analysis of
      the social, psychological, physiological and medical factors contributing to the
      cause and degree of pain and to pain behaviour, and of the extent to which the
      pain may be nociceptive (i.e., inflammatory, mechanical, or ischaemic in origin),
      neurogenic or idiopathic. Pain analysis should be followed by individualised
      treatment focused on the patient's most crucial problems, thus enhancing the
      prospect of optimal treatment outcome.

PMID- 9617168
TI  - [Male infertility--diagnosis and treatment].
AB  - Infertility is often due to subfertility in both partners. Investigations of the
      male partner includes history taking, physical examination (possibly supplemented
      with ultrasonography), and semen analysis. In addition to the sperm count, and
      sperm morphology and motility, numerous other seminal parameters are of interest.
      In particular, the acrosome reaction test and testing for seminal round cell
      subpopulations are now widely used. In the event of anomalies, causal treatment
      is preferable to symptomatic therapy. Significant future progress in the
      management of male infertility is predicated upon an improved understanding of
      the mechanisms involved in testicular differentiation and spermatogenesis.

PMID- 9617169
TI  - [Why do no physicians speak up regarding human genetic-ethical questions?].

PMID- 9617170
TI  - [The values of Nutricion Hospitalaria].

PMID- 9617171
TI  - [Antioxidants: the therapy of the future?].
AB  - In the present review piece, we analyze the formation of free radicals as a
      consequence of the cellular metabolism in aerobe organism, and the beneficious
      and harmful actions thereof on cellular structures. The balance existing between
      free radicals and the so-called antioxidant defenses, is a key factor for
      preventing the development of noxious processes at the cellular and tissue level.
      In accordance with the present scientific knowledge, the excessive production of
      free radicals in the organism, and the imbalance between the concentrations of
      these and the antioxidant defenses, may be related to processes such as aging and
      several diseases, among which we find cancer, ischemic processes, senile
      dementia, diabetes, pulmonary and pancreatic diseases, lupus erythematosus,
      cirrhosis, intestinal inflammatory disease, multiple sclerosis, arthritis,
      arteriosclerosis, cardiovascular disease, diseases of the central nervous system
      and the brain. According to the results of numerous research works conducted with
      the administration of several molecules with an antioxidant activity, one is
      beginning to see what their role will be in the pharmacological therapeutics for
      the treatment of a large number of patients such as those with burns, traumas,
      septics, shock, surgery, transplantation, radiation or chemotherapy, respiratory
      distress syndrome, AIDS, etc. We may possibly be facing a therapeutic tool which
      is of great interest in the clinical area, which shall be developed in the near
      future, as clinical trials which permit confirmation of their efficacy are
      conducted.

PMID- 9617172
TI  - [Nutritional support for the large burn patient].
AB  - Large burn patients make up a subgroup of critical patients in whom the nutro
      metabolic support reaches its maximum importance, due to the fact thermal
      aggression induces a hypermetabolic response which is prolonged until the wounds
      heal. In fact, there are few deubt with regard to the importance of nutritional
      support tin the management of these patients for reducing the complications and
      facilitating the closing of the wounds and the recovery of the patients. Thermal
      trauma induces the release of counter-regulatory hormones and of other mediators
      which favor proteineic catabolism, mainly muscular, lipolysis, and
      gluconeogenesis; as well, there is an alteration of thermoregulation, raising the
      equilibrium point. The estimate of the energetic requirements may be done by
      means of predictive equations, although these tend to over-estimate it; indirect
      calorimetry is the most exact method and this permits monitorization of the
      evolution, which is very variable in time, it gives the metabolic response to the
      thermal aggression, at the same time as permitting the analysis of the use of the
      administrated substrates. Its use has meant a dramatic decrease in the supply of
      calories administered to burn patients, with the present recommendation being 35
      40 kcal/kg/d. The supply of non-proteineic calories has also been modified: It is
      recommended that at least 60-70% of the calories administered, be in the form of
      carbohydrates, without surpassing 1600 kcal/kg/d. The optimal relation of non
      proteineic kcal:nitrogen, is 150:1. The administration route of the artificial
      nutrition support should be individualized in each patient, with the enteral
      route being the route of choice, as this is the most physiologic, the cheapest,
      and the safest; its use prevents the appearance of certain complications (Curling
      ulcer, cholecystitis, bacterial translocation); however, if his does not cover
      nutritional requirements of the burn patient, parenteral nutrition should be
      associated to this.

PMID- 9617173
TI  - [The effect of changes in nutritional status induced by age on oxidative liver
      metabolism].
AB  - INTRODUCTION: The hepatic oxidative metabolism is essential for the
      biotransformation of a large number substances, among which are found many drugs
      which are commonly used in clinical practice. The nutritional status of
      individuals has been shown to be of influence on this function. Aging produces a
      deterioration of the hepatic oxidative metabolism, without the cause for this
      situation having been clarified. Also, aging modifies the body composition of the
      individuals. The objective of this study is to evaluate whether the modifications
      which arise in the nutritive status due to age, can alter the hepatic oxidative
      capacity. MATERIAL AND METHODS: 165 elderly people of both sexes were studied,
      with an average age of 82 years, and 24 young people, with an average age of 29
      years. All participants were subjected to a clinical questionnaire, along with an
      evaluation of anthropometric, biochemical, and immunological nutritive
      parameters. The study of the oxidative metabolism was conducted by evaluating the
      kinetics of antipyrine. RESULTS: The elderly people showed a decrease in the
      antipyrine clearance rate (Ap Cl) (P < 0.001), and a lengthening of their life
      span (P < 0.05) with respect to the younger people. There was a significant
      correlation in the elderly people, between the Ap Cl and age, weight, size, the
      distribution volume, and the muscular area of the arm. A multiple regression
      analysis showed a predictive value which was independent for age, the AST, the
      lymphocytes, and size. CONCLUSION: Elderly people have a marked depression of the
      hepatic oxidative metabolism. The factors which participate in their nutritional
      situation, are of influence on this function. It is necessary to keep all the
      above in mind when it comes to prescribing drugs which require this type of
      biotransformation, in order to avoid adverse effects or drug interactions.

PMID- 9617174
TI  - [Wallstent endoprostheses implanted by fluoroscopic guidance in the palliative
      treatment of malignant esophageal obstructions and esophago-tracheal fistulas].
AB  - PURPOSE: The objective of this study was to present our experience with metallic
      stents (Wallstent) for palliation of dysphagia due to malignant esophageal
      obstruction and esophagotracheal fistula. PATIENTS AND METHODS: From August 1994
      to July 1996 20 uncovered and 6 covered stents were inserted in 16 consecutive
      patients with dysphagia grade 3 (n = 4) or grade 4 (n = 12) caused by incurable
      malignant obstructions. The obstruction was in the proximal (n = 4), in the
      middle (n = 3) and the distal (n = 9) third of the esophagus. Five patients
      presented with esophagotracheal fistula. The stent insertion was performed under
      fluoroscopic control. RESULTS: Exact positioning of the stent with reduction of
      the dysphagia was obtained in all patients. There were no complications related
      with the procedure. Esophagotracheal fistula was solved in those patients treated
      with covered stents. Six patients had recurrent dysphagia due to tumor ingrowth
      or overgrowth. In these patients an additional overlapping stent was placed. In
      latest evaluation 2 patients presented dysphagia grade I, 5 grade III, and 4
      grade IV. CONCLUSION: Implantation of stents proved to be an effective and safe
      method of palliating dysphagia and occluding esofagotracheal fistula. Placement
      of stents was feasible without major procedure-related complications.

PMID- 9617175
TI  - [Evaluation of energy metabolism in burn patients: indirect calorimetry
      predictive equations].
AB  - INTRODUCTION: Knowing the most reliable method for measuring the metabolic energy
      use (MEU), is of great importance in patients with severe burns. For the
      calculation of the energetic requirements of large burn patients, several
      predictive equations (PE's) are used, based on weight, size, age, body surface
      area (BSA), and burned body surface (BBS). Previous studies note the tendency for
      over-or underestimating the MEU, depending on whether one or another PE is used,
      which is why it is considered necessary to calculate the energy requirements in
      the most exact manner possible, which can be done by means of indirect
      calorimetry (IC). MATERIAL AND METHODS: 18 patients (14 men and 4 women) who were
      admitted to the Burn Unit between 1994 and 1995, were included in the study, with
      the following inclusion criteria; age > 18 years and < 65 years, and who
      presented deep burns on are than 15% of the body surface. The MEU of the patients
      was evaluated by means of IC, using a Deltatrac il unit. The MEU calculated by
      means of IC was compared with that calculated by means of the four most commonly
      used PE's in literature: Long Formula: MEU = Basal energy use (BEU) x activity
      factor x aggression factor which is variable according to the BBS; Curreri
      Formula: MEU = (Weight x 25) + (total BBS x 40); MEU = 2000 x BSA. As statistical
      methods, one looked for the existence of correlation, by means of the Pearson
      method, and the "r" were compared by means of the Fischer conversion. The
      regression coefficient was found among the values obtained through the PE's and
      those measured by IC, as well as among those of IC and the percentage of deep
      burn and the total burned body surface. RESULTS: All the formulate included
      overestimated the MEU measured between 30.6% and 43.8% with the 2 x MEU formula
      being the one which did so least (30.6%). In any of them, there is an important
      variation of the percentage of overestimation with respect to the average MEU in
      this group. All are correlated in an important way with the MEU. The reliability
      of these PE's is variable, as is shown by the slopes of the regression lines,
      with the most reliable PE being that of 2000 x BSA, and that of 2 x MEU, by
      Harris-Benedict. There is also correlation between the average MEU by IC and the
      deeply burned body surface. CONCLUSION: This study proves the usefulness of the
      IC for knowing the EME in burn patients, to prevent their hypernutrition, as well
      as the relative value of the formulae usually used clinically to estimate this
      parameter.

PMID- 9617176
TI  - [Alternatives to solid pharmacutical forms usually given by enteral nutrition
      tubes].
AB  - We analyze which drugs of those administered through an enteral nutrition tube,
      present problems which are inherent to the pharmaceutical forms. The study is
      conducted with a sample of 40 patients who have a feeding tube, who received a
      total of 48 different medications. 38 (78.3%) were in a solid pharmaceutical
      form, and 10 (21.7%) were liquid. Among the most used medications, ranitidine
      stands out in 12 patients, paracetamol in 8, and phenytoin in 7. We note the use
      of the solid forms of phenytoin, nifedipine, and controlled release morphine, as
      having the greatest interest due to their contraindication. For all the studied
      cases, we propose alternatives and we note those drugs for which we did not find
      any. The hospitalary pharmaceutical guides should include liquid pharmaceutical
      forms of those drugs which should not be ground up. There is little information
      on the wards about the administration of drugs through feeding tubes.

PMID- 9617177
TI  - [Results of nutritional treatment of anorexia nervosa: our experience (1989
      1995)].
AB  - With the alm of evaluating the nutritional treatment of anorexia nervosa (AN) in
      our center, evolutive data were collected, as well as anthropometric and
      biochemical parameters, of out out patient department (OPD) as well as of our
      hospital admissions (HA) which took place between 1989-91 (period A) and between
      1992-95 (period B). 79 cases of HA were included (5 men, 31 women), with a
      duration of hospitalization of 36.96 +/- 22.02 days, with the reason for release
      most often (86.84%) being reaching the agreed upon weight, and 124 cases of OPD
      (12 men and 112 women), who were followed for 11.53 +/- 12.13 months achieving a
      final release rate of 14.14%. The nutritional status (NS) of the HA patients upon
      admission was most often sever caloric malnutrition (CM) (64.55%), and upon
      release this was moderate CM (60.75%), while in the OPD the moderate CM was most
      frequent at the initial visit and at the last visit registered. The
      anthropometric parameter which was most affected, was the triceps fold (TF),
      followed by the wight (W). The biochemical abnormalities were few, with
      hypercholesterolemia and ferropenia being notable. The nutritional treatment in
      the OPD required the addition of dietary supplements in 31% of the cases, and of
      psycho-medication in 43%. In the HA cases, only 6 patients reached the agreed
      upon wight with a free oral diet, and 35 patients required dietary supplements,
      20 needed mixed therapy (enteral nutrition and supplements), and 17 cases
      required enteral nutrition through a naso-gastric tube. Significant multivariant
      models are presented which find independent associations for the probability of
      release (lower age upon diagnosis, male, lower income, absence of bulimia's, no
      need for dietary supplements), of amenorrhoea (worse NS, absence of vomiting),
      and for the HA time (more interventionist treatment, lower weight, lower age).
      The comparison between periods, shows an initial contact of the patients with AN
      with our OPD, with a better nutritional status y recent years, as well as a
      better nutritional result, a greater tendency towards the use of enteral
      nutrition, and a shorter time of HA.

PMID- 9617179
TI  - [Nutrition and oxidative hepatic metabolism].

PMID- 9617180
TI  - [As we said yesterday ... or in one place of the net].

PMID- 9617181
TI  - [Response to aggression: evaluation and therapeutic implications. Work Group on
      Metabolism and Nutrition of the SEMIUC].
AB  - The metabolic response to stress/aggression is a complex process which is mainly
      mediated by the interaction between the neuro-endocrine system and the
      circulating cytokines. This interaction brings about physiological and metabolic
      alterations--severe metabolic-nutritional deficits--of the hypermetabolic type,
      muscular proteolysis, lipolysis, glycogenolysis, and gluconeogenesis among
      others, which should be studied and understood prior to initiating or not a
      nutritional support. The parenteral or enteral nutritional support is usually
      indicated to prevent a worsening of these situations of altered metabolism
      frequently associated with inanition, although one should not attempt to revert
      to normal preexisting deficit situations. On the other hand, and is this special
      context, we should not forget the advances in nutrients with pharmacological
      effects, and in pharmacological nutrition. At this II Consensus Conference of the
      SEMIUC (Sociedad Espanola de Medicine Intensiva y Unidades Coronarias = Spanish
      Society of Intensive Medicine and Coronary Units), we have proposed four
      objectives: i) To make recommendation, based both on the scientific evidence, as
      on the experience of the components. ii) Define the scientific terminology to be
      used in this specific context. iii) Give an answer to the different and assorted
      clinical problems which are secondary to a situation of stress which has a
      multiple etiology. iv) Provide new ideas for the development of clinical trails
      and studies of this specific context.

PMID- 9617182
TI  - [Influence of the aging process on body composition of the aged: the SENECA study
      in Spain].
AB  - The maintenance of an adequate proportion of muscular mass in aging, is critical
      for the quality of life of elderly people. In the face of the lack of
      longitudinal data, the semi-longitudinal SENECA (Survey in Europe on Nutrition
      and the Elderly, a Concerted Action) study was proposed, with the aim, among
      others, of analyzing the influence of the aging process on the body composition.
      In this study, the results are presented which correspond to the changes in body
      composition seen between the baseline study and the follow up period (1989-1993),
      in the participating Spanish population, which was randomly selected, and whose
      ages were between 70 and 80 years. There is also an analysis of the relation
      existing in 1993, between different anthropometric measurements and the
      functionality evaluated objectively by means of the physical and functional
      capacity test (PPT). Using a standardized methodology, the following were
      measured: size, breadth, weight, biceps and triceps fold, and the circumference
      of the waist, hips, and the upper arm. Based on these measurements, we calculated
      the body mass index (BMI), the waist/hip ratio, the muscular circumference of the
      arm, the fat mass, and the fat free mass. The longitudinal analysis between 1989
      1993 showed a decrease for both sexes, in weight (-3.5 +/- 5.0 in men, and -3.4
      +/- 4.0 kg in women: p < 0.001) and body circumferences; and also, in women, in
      the size and the triceps fold (-0.63 +/- 1.42 cm, p < 0.01, and -3.6 +/- 4.6 mm,
      p < 0.001, respectively). Consequently, the BMI (-1.4 +/- 1.8 for men and -1.4 +/
      1.8 kg/m2 in women, p < 0.01) decreased, while the waist/hip ratio did not
      change. A reduction of the fat free mass of -1.6 +/- 2.1 kg (p < 0.01) in men and
      -1.2 +/- 1.3 kg in women (p < 0.001), was observed, as well as a reduction of the
      body fat of -1.8 +/- 2.0% and -1.7 +/- 2.6% (p < 0.001), respectively. On the
      other hand, analyzing the anthropometric measurements of the follow up study, a
      positive association was detected for men, between the waist and hip measurements
      and the functionality measured by the PPT.

PMID- 9617183
TI  - [Bilirubin-albumin binding in term newborns on total parenteral nutrition].
AB  - We evaluate the influence of plasma lipid levels supplied in parenteral
      nutrition, on the bilirubin-albumin binding of 12 term newborns with severe
      pathologies. As controls we selected 2 groups of an equal number o newborns who
      were receiving maternal or artificial lactation. The reserved albumin binding
      capacity decreased in newborns subjected to parenteral nutrition (52.3 versus
      72.9/73.5). This decrease correlated positively with greater concentrations of
      free fatty acids (r = 0.9234, p < 0.001), cholesterol (r = 0.9049, p < 0.001),
      and triglycerides (r = 0.8802, p < 0.001). The clear influence of the studied
      lipid parameters on the bilirubin albumin binding, invites us to consider the
      systematic use of heparin for the mobilization of lipoprotein-lipase from the
      vascular endothelium and to promote a better management of lipids in term
      newborns, especially if there is an important hyperbilirubinemia.

PMID- 9617184
TI  - [Nutritional status of patients with HIV infection. Spontaneous evolution during
      the hospital stay].
AB  - BASICS: Evaluate the nutritional status of HIV positive patients who are admitted
      to hospital for some acute process, and their evaluation, without nutritional
      support, during the admission. METHODS: Prospective study in HIV positive
      patients. Nutritional evaluation (on admission and on release); (1)
      anthropometric (weight, size, triceps, fold, circumference of the arm, and
      muscular circumference of the arm, and (2) biochemical (albumin, cholesterol,
      triglycerides, lymphocytes, pre-albumin, and transferrin). Statistical study:
      comparison of the paired means and chi squared test. RESULTS: 60 patients. Mean
      age 32 +/- 4.8 years, 76% men and 23% women. Staging: AIDS 84.8%, non-AIDS 15.2%.
      Main reason for admission: Infection (80%). Mean stay: 14 days +/- 9.5. Initial
      nutritional evaluation: normal: 1.7%, protein malnutrition: 5.3%, caloric
      malnutrition: 38.5%, mixed malnutrition: 54.3%, 85% of the patients refer weight
      loss. 21 patients (35%) were followed up. There were no significant differences
      in the anthropometric nor in the biochemical parameters, except in the levels of
      pre-albumin and transferrin, which improved (p < 0.001). Nutritional evaluation
      on release: normal: 9.5%, caloric malnutrition: 66.5%, mixed malnutrition: 23.7%.
      There were no cases of protein malnutrition. CONCLUSIONS: The vast majority of
      the HIV+ patients who are admitted, are malnourished, and after curing the acute
      process, 90.5% of them remain malnourished. The anthropometric measurements,
      albumin, cholesterol, and triglycerides do not vary during the hospital
      admission, despite the treatment and the clinical improvement. The increase of
      proteins with a short half life is due to controlling the infection, which is why
      these are not good parameters for the nutritional evaluation in these patients.

PMID- 9617185
TI  - [Evaluation of vitamin intake in a group of people at the University of Murcia].
AB  - The aim of this study was to evaluate the daily intake of vitamins in a group of
      adults of the University of Murcia. A sample of 116 individuals (69 men and 47
      women) aged 25 to 45 was used. Data were derived from 7-day dietary records done
      by the individuals, and the intakes of vitamins were compared with the Spanish
      Recommended Dietary Allowances. The results showed that the intake of water
      soluble vitamins was appropriate; but the intake of vitamins E and D were low in
      both sexes. The intake of vitamin A was excessive in almost 40% of the studied
      population.

PMID- 9617186
TI  - Bibliografia Internacional. Nutrition. The International Journal of Applied and
      Basic Nutritional Sciences.

PMID- 9617187
TI  - [Psychological measurement of tactile-kinesthetic perception in early childhood].
AB  - The perception theory of Affolter (1987), the theory of sensory integration of
      Ayres (1979, 1984) as well as the development theory of Piaget (1973) consider
      sensorimotor experiences as a basis for the child's cognitive development.
      Tactile-kinesthetic perception has hereby a central position. In the German
      speaking psychology, no standardized tests exist to measure the developmental age
      of tactile-kinesthetic perception in early childhood. The subtests of
      neuropsychological batteries have not been primarily constructed for young
      children, therefore they may not portray the age dependence of tactile
      kinesthetic perception exactly. That is why we have collected a pool of items,
      empirically based descriptors of tactile-kinesthetic behavior, to test this
      perceptual modality. Then we proved it in a series of pretests. The resulting
      preliminary developmental test contains 7 functions: Localization of touch,
      pressure sensibility, two-point-discrimination, finger identification, object
      stereognosis, stereognosis of object properties, and graphesthesia. It was
      administered to 111 children aged from 3;2 to 6;5 years in kindergarten. Data of
      the item analysis demonstrated that many items proved to be to easy.
      Nevertheless, the instrument is useful and measures reliably. The deficits of the
      experimental test version will now be corrected by a revision. We will start a
      detailed analysis again using the revised test.

PMID- 9617188
TI  - [Status of music therapy in inpatient pediatrics and child and adolescent
      psychiatry].
AB  - In order to study the present situation of music therapy in hospitals of
      pediatrics and of child and adolescent psychiatry in the FRG, a postal survey at
      these hospitals was performed. The personnel situation, methods of music therapy
      and indications for music therapy were examined. The data are analysed according
      to the kind and the size of hospital; they are compared to results obtained in a
      survey at out-patient pediatrics and to a similar survey from the year 1990.

PMID- 9617189
TI  - [Parent child relations problems in adoption].
AB  - Adoption always represents for the child a loss of emotional ties with
      birthparents and a development of new attachments with adoptive parents. Adoption
      can be considered as a life-time process of the members involved in the adoption
      triangle, that is birth parents, adoptive parents and the child. The article
      discusses the loss of emotional bonds from primary caretakers as a psychological
      trauma and addresses mournings difficulties in adoptees. Problems with the
      development of new attachments with adoptive parents such as loyalty conflicts
      and the revelation of the adoption are described. Family romance phantasy in
      adoption and the search for their origin by young adoptees are also explored.
      Aspects of family dynamics in the adoptive process and the specific difficulties
      adoptive parents encounter are reviewed. Preventive and therapeutic measures are
      presented.

PMID- 9617190
TI  - [Nutrition in Mexico].

PMID- 9617191
TI  - [Nutrition and development in the first semester of life].
AB  - OBJECTIVE: To study the psychomotor development of young infants from a poor and
      underfed rural community and to correlate this with the nutritional conditions of
      the mother during pregnancy and the child itself. MATERIAL AND METHODS: We
      studied 82 mother-child pairs from the 5th month of pregnancy to the 6th month of
      life of the child as to anthropometry and food consumption. The neonatal
      Brazelton test and the Bayley test at 3 and 6 months were applied to the child.
      RESULTS: Several of the neonatal psychomotor tests applied to the child correlate
      positively with the mother's weight and skin folds, as well as with the child's
      own previous weight and size. This was also true for maternal consumption of
      animal foods and fruits during pregnancy. A negative correlation was observed
      with the consumption of corn tortillas and beans. The correlation of several
      tests applied to the child at six months was positive with its complementary
      consumption, total energy and several foods, specially egg, milk and fruit around
      three months of age. CONCLUSIONS: Small variations in nutrition of the mother
      child pairs from the poor rural community studied had consequences on the
      psychomotor development of the infant. These findings point to the need for more
      applied nutrition programs.

PMID- 9617192
TI  - [Length and weight at birth: the role of maternal nutrition].
AB  - OBJECTIVE: To identify determinants of weight (BW) and length at birth (BL).
      MATERIAL AND METHODS: We studied 481 mother-newborn pairs in three Mexico City
      hospitals. Multiple regression models were developed to identify statistically
      significant predictors of BW and BL with respect to a predetermined biological
      model. Independent variables included were: maternal anthropometry, age, smoking
      habits, and civil status, parental education, obstetric history, hypertension,
      and neonatal characteristics. RESULTS: In the group with calf circumference (CC),
      height and head circumference below the median BW was 133, 92 and 96 g lower (+/-
      35 standard error -SE-, p < 0.01) than the group above the median, adjusting for
      socioeconomic, obstetric history, and neonatal characteristics (NC). In the group
      below the median CC or height, BL was 5.8 or 6.2 mm (+/- 1.9 mm SE, p < 0.01)
      respectively, adjusting for obstetric history and NC. CONCLUSIONS: Results
      suggest that maternal anthropometry is the most important predictor of birth size
      and that predictors for BW and BL differ.

PMID- 9617193
TI  - [Capacity of weight-for-age and length-for-age to predict stunting at 3 years of
      age].
AB  - OBJECTIVE: To compare the capacity of two cut-off points of weight-for-age and
      length-for-age (-1 and -2 standard deviations) at different ages in the interval
      between birth and 30 months to predict stunting in three year old children.
      MATERIAL AND METHODS: Data from a longitudinal study in Guatemala were used to
      evaluate the hypothesis that the capacity of cut-off values of weight-for-age and
      length-for-age to predict stunting at three years of age varies according to age.
      RESULTS: Length-for-age at -1 standard deviation (SD) of the WHO/NCHS mean
      reference values is a satisfactory prognostic indicator of stunting at three
      years of age during the first semester of life, while the same index at -2 SD is
      adequate after 9 months of age. Weight-for-age at -1 SD is a suitable indicator
      only at 9 months and at -2 SD the indicator is satisfactory between 15 and 24
      months of age. CONCLUSION: The capacity to predict stunting at three years of
      age, for weight-for-age and length-for-age cut-off values varies according to
      age.

PMID- 9617194
TI  - Validity and reproducibility of a food frequency questionnaire to assess dietary
      intake of women living in Mexico City.
AB  - OBJECTIVE: To assess the reproducibility and validity of a 116 item semi
      quantitative food frequency questionnaire (FFQ), designed to assess the relation
      between dietary intake and chronic diseases. MATERIAL AND METHODS: To test the
      reproducibility of the FFQ questionnaire, the FFQ was administered twice to 134
      women residing in Mexico City at an interval of approximately one year; to assess
      the validity we compared results obtained by the FFQs with those obtained by four
      4-day 24-hour recalls at three month intervals. Validity and reproducibility were
      evaluated using regression analysis and Pearson and intraclass correlation
      coefficients of log-e and calorie-adjusted nutrient scores. RESULTS: Mean values
      for intake of most nutrients assessed by the two food frequency questionnaires
      were similar. However, means for the 24-hr recall were significantly lower.
      Intraclass correlation coefficients for nutrient intakes, assessed by
      questionnaires, administered one year apart, ranged from 0.38 for cholesterol to
      0.54 for crude fiber. Correlation coefficients between energy-adjusted nutrient
      intakes, measured by diet recalls, and the first FFQ ranged from 0.12 for
      polyunsaturated fatty acids to 0.67 for saturated fatty acids. Regression
      coefficients between 24-hr recall and FFQ,s were all significant were significant
      for all nutrients, except for polyunsaturated fat, folic acid, vitamin E and
      Zinc. CONCLUSIONS: These data indicate that this semi-quantitative FFQ is
      reproducible and provides a useful estimate by which to categorize individuals by
      level of past nutrient intake. However, its application outside Mexico City or in
      different age and gender populations will require additional modifications and
      validation efforts.

PMID- 9617195
TI  - [Sustained feeding in acute diarrhea in children below 5 years of age].
AB  - OBJECTIVE: To identify locally available and culturally acceptable foods for
      children with acute diarrhea, and test their acceptance and effect on the child's
      weight. MATERIAL AND METHODS: 142 mothers of children younger than five years of
      age living in rural communities were interviewed to indentify culturally accepted
      diets by means of group sorting. These were displayed in a multidimensional
      scale. A descriptive study was performed of the clinical course of 54 children,
      ages 4 to 50 months who received the designed diets during the first 48 hours of
      diarrhea. RESULTS: The designed diets considered age of the child, and stage of
      the disease. Children spent 47.6 +/- 22.2 h in the hospital during which they
      consumed 44.8 +/- 28.6 kcal/kg/day (additional to breast milk) and they gained
      70.6 +/- 179.7 g. A direct relationship was observed between increasing age and
      larger caloric intake, and between this and greater weight gain. CONCLUSION:
      Children showed good acceptance of diets. Caloric intake was enough to prevent
      weight loss.

PMID- 9617196
TI  - [Child malnutrition in the Mexican rural setting].
AB  - OBJECTIVE: To evaluate the nutritional status of the infantile population in
      rural Mexico, compare it with previous data and situate the most affected areas.
      MATERIAL AND METHODS: The sample consisted of 38,232 families, from 855 randomly
      selected communities. Anthropometry was obtained from 31,601 children under five
      years of age and analysis was performed considering the reference values of
      weight/age, weight/height and height/age. RESULTS: Overall malnutrition affects
      42.7 of children according to weight/age indicator (CI = 1.9%). Moderate and
      severe malnutrition 22 years ago was 17.4% and now these affect 19.3%. Further
      data show that 55.9% are malnourished according to height/age, and 18.9%
      according to weight/height. CONCLUSIONS: The ENAL 96 shows that malnutrition is
      still a severe national problem which has not improved in the last 22 years. The
      areas of highest prevalence are the southern states which have mostly Indian
      population.

PMID- 9617197
TI  - [Energy and nutrient consumption in Mexican women in reproductive age].
AB  - OBJECTIVE: To analyze energy and nutrient consumption in Mexican women from 12 to
      49 years of age. MATERIAL AND METHODS: Dietetic information was gathered by a 24
      h recall from 9,101 women who participated in the National Nutrition Survey
      conducted in 1988. These data were compared with sociodemographic and physiologic
      characteristics. Nutrient consumption was compared with the Recommended Daily
      Allowances (RDA). Variance analysis and t-test were used to evaluate group
      differences. RESULTS: Mean energy consumption was 1,721 kcal per day. The diet
      consisted of 15% protein, 60% carbohydrates and 25% fat. The proportion of women
      with dietary intakes lower than 50% of the RDA was 70% for vitamin A, 75% for
      vitamin B6, 56% for vitamin C, 33% for vitamin B12, 69% for folate, 33% for
      calcium and 22% for iron. CONCLUSION: Results show important deficiencies in the
      diet, predominantly in pregnant and lactating women, in women from low
      socioeconomic levels and in rural and indigenous women of south of the Mexican
      republic.

PMID- 9617198
TI  - [Nutritional status of Guatemalan refugees below 6 years of age].
AB  - OBJECTIVE: To determine changes in the nutritional status of Guatemalan refugee
      children under six years of age, who lived in Mexico between 1982 and 1996, under
      various nutrition-related programs implemented during that period. MATERIAL AND
      METHODS: A comparative analysis of 4 cross-sectional anthropometric studies
      performed in Chiapas (1982, 1989), Quintana Roo (1989) and Campeche and Quintana
      Roo in 1996. Malnutrition prevalence by weight/age and height/age indicators was
      calculated. Odds ratio and 95% confidence intervals were estimated. The
      implemented programs to improve nutritional status and health conditions are
      described. RESULTS: In 1982, high rates of malnutrition and mortality prevailed
      among refugee children. In 1989 some had been transferred to Campeche and
      Quintana Roo and others stayed in Chiapas. Their situation had improved and
      remained so until 1996. CONCLUSIONS: The implemented programs were successful to
      control the emergency and prevent new crises. However they only managed to
      maintain similar conditions for the refugees as those which prevail among the
      Mexican indians.

PMID- 9617199
TI  - [Zinc deficiency and its functional implications].
AB  - The purpose of this article is to review theoretical aspects and research
      performed in Mexico suggesting the existence of marginal zinc deficiency in rural
      children and its consequences on health. Zinc is an indispensable nutrient for
      humans since it plays an important role in several metabolic pathways: it
      participates in the catalytic site of several enzymes, as a structural ion of
      biological membranes and is closely associated to protein synthesis, among other
      functions. It is therefore related to functional and health impairments,
      specially in children. A marginal deficiency of zinc in Mexican children is
      relevant because of its potential effects. Studies suggest that marginal zinc
      deficiency is associated to diets based on plant foods which are rich in zinc
      absorption inhibitors. Such diets are habitually consumed in rural areas and in
      poor areas of the cities. Marginal zinc deficiency was found to cause an increase
      in infectious diseases, specially diarrhea, and an impairment of the cognitive
      functions.

PMID- 9617200
TI  - The role of vitamin A in reducing child mortality and morbidity and improving
      growth.
AB  - This is an update of knowledge on the role of the vitamin A status in determining
      child mortality, morbidity and growth. Recent information confirms the earlier
      conclusion of Beaton et al. that a 23% reduction in young child mortality results
      following improvements in the vitamin A status. Studies show that the mortality
      effect is primarily due to reductions in deaths due to acute gastroenteritis and
      measles but not acute respiratory infections (ARI) and malaria. While improvement
      of the vitamin A status enhances the survival of older preschool children, it
      remains unclear whether it benefits infants (i.e. < 6 months). Vitamin A
      supplementation does not reduce the overall incidence and prevalence of common
      childhood illness; however, it reduces the incidence of more severe episodes of
      diarrhea. Also, vitamin A supplementation either during and/or immediately after
      the illness does not improve its symptomatology. Finally, contrary to earlier
      expectations, recently completed, placebo-controlled randomized interventions
      have failed to detect improvements in child growth.

PMID- 9617201
TI  - [Iron-deficiency anemia: PAHO/WHO strategies to fight it].
AB  - Iron deficiency anemia is among the greatest nutritional problems in the world.
      Although its etiology is understood and intervention at low cost is available,
      the problem persists. The present review begins with a general estimate of the
      dimensions of the problem. It suggests the necessary elements for the design,
      implementation, and measurement of the impact of iron supplementing and
      fortification as the most effective forms to intervene and diminish iron
      deficiency anemia. Several preliminary steps are proposed previous to the
      preparation of a project and several recommendations are made to be included in a
      project for fortification and iron supplementing. A list of complementary
      activities offered by PAHO/WHO as part of the package of technical cooperation is
      included.

PMID- 9617202
TI  - [Relevant features on statistics of nutrition deficiencies].

PMID- 9617203
TI  - [Regional Plan of Action of Food and Nutrition, PAHO/WHO].

PMID- 9617204
TI  - [Swiss veterinary research and development project in the Gambia: the point of
      view of the breeder concerning control of helminthiasis in livestock].
AB  - The epidemiology of nematodes in livestock in The Gambia was assessed. A
      prophylactic biannual treatment was then tested on cattle and sheep. This
      treatment resulted in a significant improvement in the reproductive performances
      (sheep: lambings/year increasing from 1.04 to 1.22 and lambs/lambing increasing
      from 1.11 to 1.19; cattle: age at first calving decreasing from 58 to 50 months)
      and, in cattle, a significant improvement of the weight (varying between 8% and
      17% in 1 to 4 year old animals). A socioeconomic study conducted in parallel
      showed that the treatment in cattle is on average profitable (benefit/cost ratio
      of 1.14) but remains a risky investment which should not be generalised
      (benefit/cost ratio would have been below 1 in more than half of the
      participating herds). In sheep, the benefit/cost ratio is high (2.47) with a low
      risk of losses (< 10%). The obstacles to the adoption by farmers of such a
      treatment and the usefulness of a pluridisciplinary approach in similar studies
      are then discussed.

PMID- 9617205
TI  - [Differential diagnosis of hypercalcemia--a retrospective study of 46 dogs].
AB  - The case records of 46 dogs with hypercalcemia were studied retrospectively. The
      most common cause of hypercalcemia was malignancy, of which the majority were
      diagnosed as having lymphosarcoma (LSA, n = 23). Interestingly only 15 had
      palpable lymphadenopathy. Other neoplasia were apocrine adenocarcinoma of the
      anal sac (n = 4), mammary adenocarcinoma (n = 2), anaplastic carcinoma (n = 1),
      and malignant histiocytosis (n = 1). Non-neoplastic reasons for hypercalcemia
      were hypoadrenocorticism (n = 5), acute renal failure (n = 2), chronic renal
      failure (n = 2), hypervitaminosis D (n = 1), and primary hyperparathyroidism (n =
      1). In 4 cases no definitive diagnosis could be obtained. Moderate to marked
      hyperphosphatemia and azotemia was found in all dogs with primary renal failure
      and in 4 of 5 dogs with hypoadrenocorticism. In contrast only 4 of 31 dogs with
      neoplasia showed (mild) hyperphosphatemia and 20 showed mild to moderate
      azotemia. Elevated PTH levels were found in dogs with primary chronic renal
      failure and with primary hyperparathyroidism, but also in one dog with neoplasia.
      Low PTH concentrations were measured in the dog with hypervitaminosis D and in 8
      cases with neoplasia. Additional three cases with neoplasia had values in the
      reference range. CONCLUSIONS: 1. The most common cause of hypercalcemia is LSA.
      Absence of palpable lymphadenopathy does not exclude LSA and further diagnostic
      steps may be necessary 2. The combination of moderate to marked hyperphosphatemia
      suggests primary renal failure or hypoadrenocorticism. 3. An elevated PTH level
      is consistent with primary hyperparathyroidism, but does not exclude other causes
      of hypercalcemia.

PMID- 9617206
TI  - [Transgenic mice in basic research].
AB  - What are transgenic mice and what do we learn from them? In this review, we focus
      on the generation of "classical" transgenic and "knock-out" mice. The
      establishment of transgenic and gene-targeted mice provides an unique tool to
      study the function(s) of a given gene in the context of a whole organism. Based
      on selected examples, we demonstrate the potential of this transgenic technology
      to understand the interactions between cells, organs and organ systems in
      genetically engineered mice.

PMID- 9617208
TI  - [Life will not be patented].

PMID- 9617207
TI  - [What is your diagnosis? Generalized tuberculosis caused by M. tuberculosis
      complex].

PMID- 9617209
TI  - [The thoracic roentgen image: emergency and routine indications in the clinic and
      general practice].
AB  - Even in the era of rapidly emerging cross-sectional imaging techniques (computed
      tomography, magnetic resonance imaging) the chest radiograph remains the most
      frequently performed diagnostic imaging procedure and has not lost any importance
      to other modalities. After technical considerations the value of chest
      radiography will be discussed based on the most widely applied indications in
      emergency and routine clinical settings and the link to subsequent imaging
      modalities will be outlined.

PMID- 9617210
TI  - [Follow-up of tumor patients].
AB  - There are two main reasons for routine follow-up examinations after treatment of
      cancer patients: 1. Assessment of treatment efficacy and detection of relapse; 2.
      rating of drug side-effects. Routine controls can only efficiently be performed
      with a profound knowledge of the biology of the tumor and of the therapeutic
      efficacy of the available treatments. The frequency and the type of the follow-up
      examinations depend mainly on the curative or the palliative treatment
      possibilities. Examples of useless controls are mentioned. Through the prevention
      of unnecessary examinations the primary care physician could play an important
      role in the cut down of health care costs.

PMID- 9617211
TI  - [Radiotherapy of epipharyngeal carcinoma: successes and limits as examples of new
      treatment strategies].
AB  - In treating cancer patients, disease free survival and survival have been
      improved during the last decade by technical progress and new systemic therapies.
      In radiation therapy as well as in any other cancer treatment potential long-term
      side effects and complications need special attention. The success of doubling
      tumour control by radiation therapy in patients with head and neck tumours
      illustrates the needs of long-term follow-ups. Cost-effectiveness has to be
      considered, when treatment results of RT equal surgical results, as it is often
      the case in head and neck tumours as well as in other malignant diseases.

PMID- 9617212
TI  - [Return from the tropics: relevant diagnosis and rational therapy].
AB  - Gastrointestinal disorders, particularly diarrhoea, are the main reason to
      consult a physician after travelling to the tropics. Although mostly of
      infectious origin specific pathogens frequently cannot be demonstrated. As the
      majority of acute diarrhoeal episodes resolve without any specific therapy,
      bacterological and parasitological investigations should initially be ordered
      with reserve and economically. Fever after a stay in the tropics has to be always
      a matter of concern as it could be the expression of a potentially dangerous
      infection, e.g. falciparum malaria. The primary objective must be the exclusion
      of potentially life-threatening infections requiring a specific treatment.
      Numerous asymptomatic travellers returning from the tropics want their physicians
      to exclude an inapparent exotic infection. The value of such check-ups can be
      questioned, and there are just a few rational investigations in this particular
      context.

PMID- 9617213
TI  - [Hypertensive derailment in marital crisis].
AB  - A 34-year-old man was admitted because of headache with neck pain, hypertension
      and tachycardia. The symptoms started 10 days prior to presentation. In the past
      the patient was treated because of different vegetative symptoms, which were
      interpreted in relation to excessive private problems. Despite suggestive
      clinical presentation, the diagnosis phaeochromocytoma was confirmed late.
      Following removal of the tumor, blood pressure came into the normal range. The
      operation also abolished all vegetative symptoms and lead to stabilisation of the
      psychosocial situation.

PMID- 9617214
TI  - [Informative material on HIV/AIDS for adolescents and parents].

PMID- 9617215
TI  - [Psychosis in AIDS].

PMID- 9617216
TI  - [Diffuse muscle pain].

PMID- 9617217
TI  - [Functional domain and its receptor of osteopontin].

PMID- 9617219
TI  - [Dof proteins: involvement of transcription factors with a novel DNA-binding
      domain in tissue-specific and signal-responsive gene expression].

PMID- 9617218
TI  - [Implication of collagens in organogenesis].

PMID- 9617220
TI  - [Recent progress and prospects of the research on the signal transducing enzyme
      phospholipase D].

PMID- 9617221
TI  - [Transcription factor forkhead family].

PMID- 9617222
TI  - [Mechanisms of induction and identity formation in brain development].

PMID- 9617223
TI  - [Foreign gene expression in fission yeast S. pombe].

PMID- 9617224
TI  - [Bombyxin, an insect insulin-related peptide which has a prothoracicotropic
      activity].

PMID- 9617301
TI  - Infectious diseases and the ER physician: expect the unexpected. Interview by
      Marc Kennedy.

PMID- 9617302
TI  - A new reason to be nervous about ticks. Interview by Marc Kennedy.

PMID- 9617303
TI  - Infectious diseases in Wisconsin.

PMID- 9617304
TI  - Sulfa hypersensitivity in patients with HIV infection: onset, treatment, critical
      review of the literature.
AB  - Trimethoprim/Sulfamethoxazole is the most effective medication used in both the
      treatment and prevention of Pneumocystis carinii pneumonia (PCP) in patients with
      HIV/AIDS. Its use, however, is accompanied by a high incidence of adverse
      reactions, especially fever, myalgia and rash (sulfa hypersensitivity). In a
      group of our patients, we have examined the clinical parameters at the time of
      onset of sulfa hypersensitivity, and the success of a desensitization protocol
      for this adverse event. We also have performed a comprehensive review of the
      literature on sulfa hypersensitivity and have compared our results to those
      previously reported in the literature. Our findings indicate that the sulfa
      hypersensitivity reaction is more likely to develop in patients with advanced
      disease and that desensitization can restore tolerability to the drug in
      approximately two thirds of those who attempt it.

PMID- 9617305
TI  - HIV seroprevalence among male prison inmates in the Wisconsin Correctional
      System.
AB  - OBJECTIVE: To estimate HIV seroprevalence and the acceptance of voluntary HIV
      testing among male inmates entering the Wisconsin Correctional System during July
      1, 1994-June 30, 1995, and compare these estimates with similar data obtained in
      1987-1988. METHODS: A blinded HIV seroprevalence survey concurrent with a review
      of voluntary HIV antibody testing records. RESULTS: HIV test results were
      obtained for 3,681 (89%) male prison entrants during the study period; 26 (0.7%)
      were HIV-1 seropositive. Based on this estimate and the total number of male
      prison entrants (4,134), an estimated 29 HIV-1 seropositive male inmates entered
      the Wisconsin Correctional System during the study period. Eighty-four percent of
      all inmates were tested voluntarily. Among inmates testing HIV-1 seropositive,
      69% were tested voluntarily. CONCLUSIONS: These data suggest that HIV-1
      seroprevalence among male prison inmates in Wisconsin is low, and is unchanged
      from the late 1980s; however, a large increase in the prison population has
      resulted in a substantial increase in the absolute number of HIV-1 seropositive
      inmates entering the correctional system. Although overall acceptance of
      voluntary HIV testing is high, nearly one third of HIV-1 seropositive inmates
      declined voluntary HIV testing.

PMID- 9617306
TI  - Hepatitis A infections in Wisconsin: trends in incidence and factors affecting
      surveillance, 1986-1995.
AB  - From January 1986 through December 1995, 4,143 cases of hepatitis A virus (HAV)
      infection were reported in Wisconsin. The annual hepatitis A incidence remained
      stable from 1986 through 1988, with a mean annual rate of 4.7 cases per 100,000
      (endemic HAV incidence rate). During 1989-1993, the incidence of HAV infection
      increased with a peak in 1992 of 19 cases per 100,000 population. A large
      foodborne outbreak (1992) and community wide outbreaks among African American
      residents (1989-1993) and Native Americans residents (1991) were associated with
      these high rates of HAV infection. The community wide outbreaks affected
      different groups: among African Americans, incidence rates were highest in young
      adults 15-34 years old; among Native Americans rates were highest in children 5
      14 years old. Approximately 2,343 (57%) patients had no apparent risk factor
      (e.g., international travel, contact with person with HAV infection) for
      acquiring HAV infection. Factors limiting control of HAV infection in Wisconsin
      included poor reporting by laboratories (only 19% of all reported cases were
      independently reported to the Wisconsin Division of Health by a laboratory and
      fewer than 50% of these reports were from private laboratories), incomplete
      reporting by Wisconsin physicians or designees (74% of cases confirmed in
      Wisconsin laboratories were reported in 1995), failure to submit follow-up case
      report forms (14% of cases), and a prolonged interval between diagnosis and
      follow-up (> or = 15 days for 610 cases). Efforts should be enhanced to improve
      the reporting of cases of HAV infection by private laboratories, particularly
      through the use of automated electronic reporting.

PMID- 9617307
TI  - An adult male with group B Streptococcus bacteremia, meningitis, and
      endocarditis.

PMID- 9617308
TI  - The importance of multiple antibiotic coverage for hospitalized patients when the
      community acquired pneumonia is Legionnaire's disease.

PMID- 9617309
TI  - Epidemiology of human blastomycosis in Vilas County, Wisconsin. II: 1991-1996.
AB  - PURPOSE: A previous report identified Vilas County, Wisconsin, as an area highly
      endemic for blastomycosis based on a case series 1979-90. This study was done to
      compare the epidemiologic features of persons with this disease over the
      following six years. METHODS: Compilation of data from the 47 mandatory
      physician/laboratory case reports of blastomycosis, disease onset 1991-96,
      received at the Vilas County Health Department; case mapping by site visit; and
      statistical comparison to the previous series. RESULTS: The estimated mean annual
      incidence rate for Vilas County during 1991-96, 40/100,000, remains unchanged
      from 1984-90. Cases were again disproportionately represented in the southeast
      corner of the county, and 36/46 lived within 1/4 mile of water. There was a trend
      toward a higher proportion of female cases in this study (27/47) compared to the
      prior report (28/73; P = 0.06); the mean age, 47 years, did not differ. Among 32
      patients whose activities were recorded, a minority engaged in hunting (4),
      fishing (4) and gardening (12) prior to disease onset; but 19/32 recalled
      excavation prior to exposure compared to 17/60 in 1979-90 (P < 0.01). Among cases
      with a pulmonary presentation, winter onset cases (3/40) were significantly fewer
      than in 1979-90 (19/55). However, over the entire 18 years there was no
      disproportionately represented season. CONCLUSIONS: In highly endemic Vilas
      County, the mean annual incidence of human blastomycosis appears stable over the
      past 13 years. A combined case series of 18 years reveals no predilection by
      gender or season of onset.

PMID- 9617310
TI  - Beware of the fungus.

PMID- 9617311
TI  - Sporadic cases of hemorrhagic colitis associated with Escherichia coli O157:H7 in
      rural Wisconsin.
AB  - The epidemiology and clinical aspects of Escherichia coli O157:H7 (E. coli
      O157:H7) infections in rural Wisconsin have rarely been reported. In the last six
      years, 66 cases of E. coli O157:H7 infection were encountered at our institution.
      Bloody diarrhea was the universal presentation and all cases represented apparent
      sporadic infection as institutional or community-wide outbreaks were not found in
      our study. The mean age was 31 (range 7 months to 86 years), 25% less than 10
      years old and 60% were female. Most cases were seen in summer and early autumn
      (88%). Two patients (3%) developed hemolytic-uremic syndrome. Case-fatality rate
      in this study was 1.5%. Antibiotic treatment and hospitalization did not change
      the course and outcome of the infection. Routine screening of E. coli O157:H7
      during winter time (December and January) may not be necessary in our rural area.
      The understanding gained from our study might foster better infection control.

PMID- 9617312
TI  - The Wisconsin Primary Care Organizations Consortium: a forum for the primary care
      medical specialties.
AB  - The Wisconsin Primary Care Organizations Consortium (WI-PCOC) is composed of the
      leadership of Wisconsin's primary care medical specialties whose four
      professional societies have a combined membership of about 3,900 physicians.
      Since 1992, WI-PCOC has explored the priorities and issues of importance of each
      organization, and has reviewed organizational resources to synchronize agendas
      and to avoid conflict. WIPCOC articulates policy supported by its member
      societies with a common voice; it does not set policy. WI-PCOC has worked with
      legislators, medical school deans, other specialty societies and other groups
      interested in primary care service and education. WI-PCOC member organizations
      aspire to work together to improve the level of health of Wisconsin citizens and
      their communities.

PMID- 9617313
TI  - A helpful extension of the HIV law.

PMID- 9617314
TI  - [Cancer prevention by stopping smoking].
AB  - Many epidemiological studies have revealed that cigarette smoking is associated
      with lung cancer and several other cancers and that the risk of lung cancer
      decreased after smoking cessation. The risk attributable to smoking from cancer
      can be calculated from the relative risk for smokers and the proportion of
      smokers in a given population. In Japan 26.7% of cancer of all sites was
      attributable to smoking among males, whereas only 4.4% was attributable to
      smoking in females, mainly because of their lower smoking frequency. It was also
      estimated that if the smoking rate was decreased from the present level of 56.1%
      to 40% and 20%, 7.7% and 17.2% of cancers of all sites could be prevented in
      males. The preventable fraction of cancer in females was small (1.4% and 2.9%)
      even if the smoking rate was decreased from the present level of 14.5% to 10% and
      5%. Among males, 65.9% of lung cancer was considered attributable to smoking, and
      were the smoking rate decreased from the present level of 56.1% to 40% and 20%,
      up to 18.9% and 42.4% of lung cancer could be prevented. In view of the recent
      remarkable increase of lung cancer in Japan and the relatively low mortality
      reducing efficacy of lung cancer screening, it is necessary to promote primary
      prevention of lung cancer and of other smoking-related cancerous and non
      cancerous diseases by extensive smoking control.

PMID- 9617315
TI  - [New cancer therapies: balancing risk and benefit].
AB  - Irinotecan has been approved in Japan, France and USA, however, its clinical
      usefulness seems to be differently understood. There is a strong opinion,
      especially in Japan, that the drug is too toxic since it may harm as many
      patients than it helps. On the contrary, irinotecan is well accepted to the US
      cancer chemotherapy practices. With irinotecan as a typical example of new
      chemotherapeutic agents, benefit and risk of cancer chemotherapy is discussed.
      Differences in cancer chemotherapy practices between Japan and USA are discussed
      as well.

PMID- 9617316
TI  - [Molecular biological aspect].
AB  - Although adenocarcinoma of the prostate is recently becoming one of most common
      malignancies in Japanese men, it still poses many questions regarding its
      etiology, pathology, pathogenesis and clinical management. Many reports have been
      made on oncogene and tumor suppressor gene, however, frequent genetic alterations
      have not been identified during prostate cancer development. Loss of
      heterozygosity (LOH) on 8p might be an important event in the early stage of
      prostatic carcinogenesis, whereas alteration in 17p is now considered a late
      event. Numerous reports about the androgen receptor (AR) gene have revealed that
      mutations in the coding region of AR possibly results in an acquired resistance
      to androgen blockade therapy and anti-androgen withdrawal syndrome. It has been
      also shown that shorter CAG repeats of AR gene are associated with a higher risk
      of prostate cancer. Regarding molecular diagnosis, prostate-specific membrane
      antigen (PSM) appears to be a new molecule with many potentially valuable
      applications. PSM-reverse transcriptase-polymerase chain reaction (RT-PCR) is
      probably more sensitive and specific than PSA-RT-PCR to predict micrometastatic
      disease. Gene therapy based on the above molecular aspect is currently under
      investigation but not generally used yet.

PMID- 9617317
TI  - [Mass screening for prostate cancer--how to eliminate clinically insignificant
      cancer].
AB  - The ultimate aim of the mass screening program for prostate cancer is to decrease
      prostate cancer mortality, which can be demonstrated only in a well-designed and
      well-controlled trial comparing screened and unscreened populations. However, no
      trials have been performed to demonstrate the effect of this program. Some
      reports claimed that such a program includes the high possibility of detecting
      clinically insignificant cancer, for example, latent cancer. In this paper, early
      cancer detection and treatment in mass screening program are discussed.

PMID- 9617318
TI  - [Prostatectomy for prostate cancers].
AB  - Radical prostatectomy may afford cure in men in whom the malignancy is completely
      extirpable. Historical experiences as well as ours agreed that long term survival
      after radical prostatectomy was excellent if the disease was confined to the
      organ. Cure may also be expected in some selected patients with minimal extra
      organ invasion. Furthermore, preoperative hormonal therapy may improve the cure
      rate in these invasive diseases. However, if cure means affording the patient the
      best chance of dying of some causes other than cancer, some of those extirpable
      diseases may be cured without surgery. This idea was supported by epidemiologic
      data on the natural history of the disease, and retrospective observations of
      conservatively treated patients. Challenging issues toward the 21st century are
      to expand the range of surgically curative diseases, and to identify diseases
      extirpable but predestined never to kill the host during the natural course of
      his life.

PMID- 9617319
TI  - [Endocrine therapy for prostate cancer in the future].
AB  - Endocrine therapy for prostate cancer has been changing rapidly. While LH-RH
      agonists have been popularly used in medication, their long-acting sustained
      release formulation is about to be introduced to clinics in Japan. LH-RH
      antagonists, which have not attracted much attention of clinicians because of
      adverse reactions, are also going to be put into practical use in the near
      future. Bicalutamide, which is considered to have greater usefulness than other
      anti-androgens, is now under regulatory review by the authorities for approval.
      In addition, a broader range of endocrine therapies is being studied for
      treatment of prostate cancer. In terms of treatment methods, a number of attempts
      are made in selection of subject patients, treatment timing, combination
      treatment and so on.

PMID- 9617320
TI  - [Radiotherapy: a significant treatment option in management of prostatic cancer].
AB  - In the management of patients with localized prostate cancer, both radical
      prostatectomy and radiotherapy are shown in the U.S. to be equally effective to
      control a local disease but associate with different types of toxicity.
      Therefore, both treatments are recommended for patients to choose freely.
      Recently, mainly in western countries, radiotherapy has achieved technological
      innovation so as to increase target tumor doses and to decrease the volume and
      dose of peritumoral normal tissues, by which the treatment outcome is further
      improved. Major innovative techniques include three-dimensional conformal
      radiotherapy (3D CRT) and a high dose-rate (HDR) brachytherapy system. Three-D
      CRT focuses radiation on the tumor through multiple portals minutely tailored to
      the tumor volume determined by computed tomography, in conjunction with a
      sophisticated treatment planning system. A HDR brachytherapy system provides high
      tech interstitial radiotherapy; a remote afterloading system precludes radiation
      exposure of hospital workers and a computer-controlled source-scanning system
      enables optimization of dose distribution. In order to provide a variety of
      effective treatment options for Japanese patients, radiation oncologists must
      master these techniques in practice, in cooperation with urologists.

PMID- 9617321
TI  - [Antitumor activity of miproxifene phosphate (TAT-59) against human mammary
      carcinoma].
AB  - DP-TAT-59, an active metabolite of miproxifene phosphate (TAT-59), showed a
      strong anti-proliferating activity against ER-positive human mammary carcinoma
      cell lines, MCF-7 and T-47D, in the presence of 1 nM of estradiol. The ED50 value
      of DP-TAT-59 for each cell line was 30-fold lower than that of tamoxifen. TAT-59
      suppressed the growth of mammary carcinoma, MCF-7 and Br-10, xenografted into
      nude mouse at a dose of 5 mg/kg/day, which is equivalent to 20 mg/body of daily
      dose to the patients. TAT-59 inhibited the growth of tamoxifen-resistant breast
      cancer cell lines, R-27 and FST-1, but not tamoxifen, suggesting the possible
      efficacy of TAT-59 for tamoxifen-refractory patients. DP-TAT-59 and DM-DP-TAT-59,
      major metabolites of TAT-59 detected in blood after oral administration in the
      patients, exhibited equal growth-inhibitory activity against human mammary tumor
      xenograft, meaning the antitumor activity of TAT-59 may equally depend on these
      two metabolites. In uterotrophic testing using both immature mice and
      ovariectomized rats, while the effective dose of TAT-59 was lower than that of
      tamoxifen, TAT-59 showed dose-dependent estrogenic activity against their uteri,
      similar to tamoxifen. These results suggested that TAT-59 had a stronger
      antagonistic activity against estrogen-dependent mammary tumor than tamoxifen. We
      expect that TAT-59 will become an effective therapeutic agent for patients with
      high estrogen levels in their blood, such as premenopausal women, and the
      patients with whom the tamoxifen modality failed.

PMID- 9617322
TI  - [Hepatocyte growth factor (HGF) in fluid from operation fields of breast
      surgery].
AB  - Recently, it is suggested that hepatocyte growth factor (HGF) is produced by
      fibroblasts with Interleukin-1. Therefore tumor cells seem to be promoted by HGF
      in the operation fields. We measured HGF in serum and fluid from operation
      fields, and evaluated its clinical significance. Fifty-one breast cancer patients
      who underwent breast surgery were enrolled. Serum HGF was measured on the day
      before operation and on the first, fifth and seventh postoperative days and fluid
      HGF on the first and fifth postoperative days, both by ELISA method. Fluid HGF
      was 10-12 fold higher than serum HGF. This result indicated that fibroblasts in
      the operation fields probably produced HGF. Moreover, invasive surgery and long
      operation time induced higher HGF concentrations. Serum HGF concentrations were
      higher in stage IV cases than in stage I-III cases. This probably means that not
      only fibroblasts but also breast cancer tissues secrete HGF. Fluid addition to
      the culture promoted MCF-7 cells in cultivation. We suggest that HGF was produced
      in the operation fields by fibroblasts and that HGF promotes tumor cells.

PMID- 9617323
TI  - [Analysis of 18 breast cancer patients with hypercalcemia].
AB  - A total of 91 breast cancer patients died of advanced and recurrent breast cancer
      at the Osaka Teishin Hospital from 1986 to 1996. There were 18 cases (19.8%)
      among them showing hypercalcemia (serum corrected Ca > or = 11.0 mg/dl). These 18
      cases were analyzed to determine the incidence of hypercalcemia and to find a
      more effective treatment. All these patients had multiple bone metastases during
      their clinical course, and six patients (33.3%) had pathologic bone fracture just
      before the occurrence of hypercalcemia. Their common symptoms were general
      fatigue, gastrointestinal symptoms, renal dysfunction or neurological symptoms.
      There was no definitive correlation between clinical signs and serum calcium
      values. Among various therapies, the use of pamidronate disodium (Aredia) in
      combination with hydration, steroid and calcitonin was found to be the most
      effective treatment for hypercalcemia. The survival time from the diagnosis of
      hypercalcemia in the patients undergoing treatment with Aredia was significantly
      better than without it (p < 0.01). This suggests that Aredia should be effective
      and useful for advanced breast cancer patients with hypercalcemia.

PMID- 9617324
TI  - [Early phase II study of TAT-59 in patients with advanced or recurrent breast
      cancer--a multicenter dose finding study].
AB  - A dose finding early phase II study of TAT-59, a new triphenylethylene
      derivative, was performed in patients with advanced or recurrent breast cancer.
      TAT-59 was given orally for over 8 weeks at a daily dose of 10 mg, 20 mg or 40
      mg/day. Thirty-six, 38 and 35 patients were eligible in the group treated with
      10, 20 and 40 mg of TAT-59, respectively. The proportion of patients obtaining a
      complete or partial response with 10 mg/day, 20 mg/day and 40 mg/day of TAT-59
      was 28.6% (10/35), 28.6% (10/35) and 25.8% (8/31) in the evaluable cases,
      respectively. The median duration of initial response with TAT-59 was 38.5 days,
      26.5 days and 25.6 days, respectively. The frequent adverse reactions observed in
      all dosing groups included hot flashes, anorexia, nausea and vomiting, sweating,
      and abnormal values in liver function tests. In these adverse reactions, the
      incidence of hot flashes, which might be caused by the pharmacologic function of
      TAT-59 was 0.0% (0 of 35), 2.9% (1 of 35) and 10.0% (3 of 30) in the evaluable
      cases receiving 10 mg, 20 mg and 40 mg of TAT-59, respectively. In conclusion, it
      was recommended that the optimal dose in terms of efficacy and adverse reactions
      should be 20 mg/day.

PMID- 9617325
TI  - [Hepatic arterial infusion chemotherapy (HAI) for advanced hepatocellular
      carcinoma inefficacious with transcatheter arterial embolization (TAE)].
AB  - For 6 patients with advanced hepatocellular carcinoma (HCC) in whom TAE was
      inefficacious, we tried hepatic arterial infusion chemotherapy. 5-FU 500 mg/day +
      CDDP 10 mg/day was administered during 5 days. The AFP level was decreased for 4
      patients, and 2 patients showed a partial response in CT image. These 2 patients
      have been alive over 22 and 18 months, respectively. These results suggest that 5
      FU + CDDP HAI might be a useful treatment of HCC inefficacious with TAE.

PMID- 9617326
TI  - [Combination of transcatheter arterial infusion of SMANCS and embolization
      (SMANCS-TAE) for hepatocellular carcinoma--second report].
AB  - Patients with unresectable hepatocellular carcinoma (hepatoma) with
      hypervascularity were treated by SMANCS-TAE. A superselective catheterization
      technique was used to inject gelatin sponge particles after administration of
      SMANCS. In 30 patients of first hepatoma treated by SMANCS-TAE. Grade 4 was
      obtained after 1.7(1-3) courses. The 2-year survival rate was 22%. Some of the 24
      patients of second hepatoma treated by SMANCS-TAE have survived over 2 years.
      Sixteen patients with advanced hepatoma (Vp2-3 or T4) were treated only by SMANCS
      injection, but none survived over 1 year. SMANCS-TAE appears to have the same
      potential and safety as L-TAE, when used selectively. Moreover, we can reduce the
      course of treatment and obtain good QOL for hepatoma patients except in advanced
      cases.

PMID- 9617327
TI  - [Experimental study on 5-FU intraperitoneal injection for liver metastasis].
AB  - The 5-FU concentrations in peripheral blood and portal blood were determined in
      rats after 5-FU injection via three routes. Rats were given 1 ml of 5-FU (250
      mg/kg) via the subphrenic, Douglas or intravenous routes. From comparison of 5-FU
      concentrations between the intravenous injection group and the intraperitoneal
      group (subphrenic injection group + Douglas injection group), the intraperitoneal
      group had a lower concentration than the intravenous one in peripheral blood. The
      intraperitoneal group showed a higher concentration than the intravenous one in
      portal blood. The intraperitoneal group was divided into two groups, a subphrenic
      injection group and a Douglas injection group. Though there was no significant
      difference between the 2 groups in the 5-FU concentrations in portal blood, the 5
      FU concentration of peripheral blood in subphrenic injection group was
      significantly higher than in the Douglas injection group. It was conceivable that
      the subphrenic injection group had another absorption route from the abdominal
      cavity to the peripheral blood. Accordingly, the intraperitoneal injection of the
      agent may be useful therapy for liver metastasis. However, due care must be given
      to the injection lesion in the abdominal cavity, the concentration and volume of
      the agent.

PMID- 9617328
TI  - [Adjuvant chemotherapy with UFT or UFT with OK-432 to patients with gastric and
      colorectal cancer. Kanto Adjuvant Study Group].
AB  - In Japan, long-term oral therapy with tegafur in combination with
      immunopotentiators is commonly used as adjuvant therapy after curative resection
      of gastric or colorectal can for gastric and colorectal cancer. When the outcome
      was analyzed in terms of the relative performance (R.P.) and the individual dose
      intensity (I.D.I.) of OK-432, gastric cancer patients with a R.P. of 0.5 or
      higher tended to have a better survival curve. There were no marked differences
      in lymphocytes subsets, except that the Leu 7 level at 3 months after gastric
      cancer resection was significantly higher (p < 0.05) in group B than in group A.
      Thus, no inhibition of the anticancer effect of UFT was noted during long term
      combination therapy with UFT and an immunopotentiator as postoperative adjuvant
      therapy for patients who underwent curative resection of gastric or colorectal
      cancer. The results suggest that UFT combined with long-term OK-432 maintenance
      therapy may contribute to improve survival rates in gastric cancer patients.

PMID- 9617329
TI  - [The evaluation of weekly hepatic arterial infusion of high-dose 5-FU for liver
      metastases from colorectal cancer].
AB  - A study was conducted on weekly infusion of high-dose 5-FU through the hepatic
      artery for liver metastases from colorectal cancer. In the evaluation of 38
      cases, no CR and 16 PR were to control the extrahepatic metastases is a subject
      for forthcoming study.

PMID- 9617330
TI  - [Combination effect of granisetron plus corticosteroid for prevention of
      cisplatin-induced emesis: a cross-over study comparing methylprednisolone and
      dexamethasone].
AB  - Granisetron (G) is an effective antiemetic drug that is used to prevent cisplatin
      induced emesis, although it is less effective for delayed emesis. To enhance the
      antiemetic effects of granisetron, corticosteroid analogues such as
      methylprednisolone (M) and dexamethasone (D) were employed in a study of patients
      treated with cisplatin (CDDP). We investigated the clinical response and urinary
      excretion of 5-hydroxyindole acetic acid (5-HIAA), the main metabolite of
      serotonin, in 31 patients with ovarian cancer or uterine endometrial cancer who
      received CAP therapy (CDDP 75 mg/m2) in a 3-day cross-over trial comparing G + M
      and G + D treated patients. Both regimens were and delayed emesis than G + D. We
      conclude that G + D is a more efficacious combination than G + D in protecting
      patients from CDDP-induced acute and delayed emesis.

PMID- 9617331
TI  - [A case report of esophageal carcinoma with grade 3 response by preoperative
      chemotherapy using CDDP/5-FU/LV].
AB  - A 67-year-old man was diagnosed as having a type 3 advanced esophageal carcinoma
      by barium swallow and endoscopy. Biopsy specimens showed well-differentiated
      squamous cell carcinoma with positive immunostaining for p53, C-erb B-2 and
      negative for bcl-2. Two courses of chemotherapy using 5-FU, leucovorin and CDDP
      were performed before operation. Because no cancer cells were present in the
      surgical specimens, the effect was evaluated as grade 3. This neoadjuvant
      chemotherapy may be effective for esophageal carcinoma with a possible apoptosis
      mechanism.

PMID- 9617332
TI  - [Advanced gastric cancer curatively resected following combined neoadjuvant
      chemotherapy--report of a case].
AB  - An advanced gastric cancer patient with T3N1M0 successfully underwent a
      curatively total gastrectomy combined with distal pancreatectomy and lymphnode
      dissection following ELF-P combined chemotherapy. The patient received two
      courses of etoposide (75 mg/m2, Day 1-5, i.v.), leucovorin (30 mg/body, Day 2-5,
      i.v.), 5-FU (500 mg/m2, Day 2-5, i.v.) and CDDP (60 mg/m2, Day 1, i.v.). A
      partial response for the primary lesion and lymphnode metastasis was obtained,
      and a successful curative resection of the stomach was performed. No drug adverse
      responses occurred. The effect of ELF-P chemotherapy was confirmed with grade 1b
      by histopathological examinations. Neoadjuvant chemotherapy with ELF-P may be
      useful as an inductive approach for advanced gastric cancer.

PMID- 9617333
TI  - [A case of gastric cancer with peritonitis carcinomatosa and malignant biliary
      stenosis treated by intraperitoneal CDDP and MMC with UFT therapy].
AB  - A 55-year-old man, who complained of vomiting, was diagnosed as having a Borrmann
      type 3 gastric cancer (T3N3P2H0M0: Stage IVb). He was treated by distal
      gastrectomy. After four months, PTCD was applied for malignant biliary stenosis
      due to lymphnode metastasis. Since ascites due to peritonitis carcinomatosa
      developed about six months after operation, UFT therapy combined with CDDP 50 mg
      and MMC 10 mg intraperitoneally were performed. The patient became gradually less
      aware of subjective symptoms after chemotherapy. Three months later, he enjoyed a
      good general condition and all of the fixed tubes were removed. This chemotherapy
      seemed effective to support his quality of life.

PMID- 9617334
TI  - [Successful treatment of pseudomyxoma peritonei using combination chemotherapy of
      intraperitoneal low-dose CDDP and oral 5'-DFUR administration].
AB  - We report a case of pseudomyxoma peritonei treated with combination chemotherapy.
      A 73-year-old woman was diagnosed as having psuedomyxoma peritonei originated
      from the vermiform appendix. Appendectomy was performed, and 10 mg of MMC was
      administered intraperitoneally. From day 7, 600 mg/day of 5'-DFUR was orally
      given for 2 years, and 20 mg of CDDP once a month was intraperitoneally
      administered seven times. The patient has been doing well with no evidence of
      tumor recurrence for two years after operation. Combination chemotherapy with
      CDDP and 5'-DFUR, as a biochemical modulation therapy, has fewer side effects and
      leads to better quality of life of patients. We recommend a combination
      chemotherapy with low-dose CDDP and 5'-DFUR for patients in poor general
      condition.

PMID- 9617335
TI  - [CDDP-resistant early recurrent uterine cervical cancer successfully treated with
      low-dose oral etoposide: a case report].
AB  - A 36-year-old woman with early recurrence of uterine cervical cancer had received
      radiotherapy and a CDDP-containing chemotherapy regimen. She was treated with
      oral etoposide by administration of 50 mg/day for 21 consecutive days at 14-day
      intervals. After two courses, complete remission was demonstrated by
      disappearance of the cervical tumor mass and pelvic lymph node enlargement on
      MRI. Leukopenia (grade 3) occurred after five courses, as well as alopecia (grade
      2) and gastrointestinal discomfort (grade 1) after two courses. The patient has
      shown no sign of recurrence for 1.5 years. This method might be quite effective
      for patients with recurrent cervical cancer as well as allowing outpatient
      treatment and improving the quality of life.

PMID- 9617336
TI  - [TNM classification of brain tumor].
AB  - TM staging proposed by UICC was classified mainly by histology and tumor size
      (extension). Staging trial was done by using the data of astrocytic tumor cases
      of the supratentorial region collected both during the periods between 1978 to
      1987 by the Brain Tumor Registry of Japan (Permission for publication: Sep.
      1994). Survival curves classified by T classification in each histology, such as
      astrocytoma, malignant astrocytoma, glioblastoma, showed a great differences from
      each other, even at the same T4 group of each histology. In this sense, the cases
      in stage IV should not be discussed as a whole, but in the way apart according to
      each histological group.

PMID- 9617337
TI  - Molecular analysis of a Myc antagonist, ROX/Mnt, at 17p13.3 in human lung
      cancers.
AB  - The chromosome region 17p13 is known to be frequently deleted in lung cancers. We
      recently showed the presence of an independent, commonly deleted region at
      17p13.3, suggesting that in addition to p53 at 17p13.1 an as-yet-unidentified
      tumor suppressor gene may reside in this telomeric region. Interestingly, the
      chromosomal location of a recently isolated novel myc antagonist gene, termed
      ROX/Mnt, coincides exactly with the centromeric border of the commonly deleted
      region at 17p13.3 in lung cancers. In conjunction with the generally acknowledged
      roles of myc genes in the pathogenesis of lung cancers, these findings led us to
      investigate whether ROX/Mnt is altered in lung cancers. Despite an extensive
      search for alterations in 52 lung cancer specimens. somatic mutations of ROX/Mnt
      could not be identified. We conclude that ROX/Mnt itself is not a frequent target
      for 17p13.3 deletions in lung cancers and that further explorations are required
      to identify the putative tumor suppressor gene at 17p13.3.

PMID- 9617338
TI  - Improvement of transduction efficiency of recombinant adeno-associated virus
      vector by entrapment in multilamellar liposomes.
AB  - Recombinant adeno-associated virus (AAV) has attracted considerable interest as a
      potential vector for human gene therapy, but its transduction efficiency is quite
      low. The present study demonstrated AAV vector-associated liposomes to be more
      effective for in vitro gene transfer to human glioma cells than are liposomes
      containing plasmid DNA. Using vector-associated liposomes increased the
      transduction efficiency more than 10-fold compared to liposomes containing
      plasmid DNA and more than 6-fold compared to AAV alone. From these results, AAV
      vector-associated liposomes appear to be a good candidate for in vivo gene
      delivery to human gliomas.

PMID- 9617339
TI  - The relationship between population density and cancer mortality in Taiwan.
AB  - Many investigators have examined urbanization gradients in cancer rates. The
      purpose of this report was to identify urban-rural trends in cancer mortality
      rates (1982-1991) for municipalities in Taiwan. For this purpose, Taiwan's
      municipalities were classified as rural, suburban, urban, or metropolitan, using
      population density as an ordinal indicator of the degree of urbanization. Average
      annual age-adjusted, site-specific cancer mortality rates were calculated for
      both sexes within each population density group. Significant increasing trends
      with more urbanization were observed in mortality rates for cancers of the lung,
      pancreas, and kidney among both males and females, as well as male prostate
      cancer, and female breast and ovary cancer. In addition, this study revealed a
      significant rural excess for nonmelanoma skin cancer among both males and
      females, as well as male non-Hodgkin's lymphoma, and cancers of the female bone,
      and female connective tissue. Analytic studies for sites with consistent urban
      rural trends may be fruitful in identifying the aspect of population density, or
      other unmeasured factors, that contribute to these trends.

PMID- 9617340
TI  - Inhibitory effects of curcumin and tetrahydrocurcuminoids on the tumor promoter
      induced reactive oxygen species generation in leukocytes in vitro and in vivo.
AB  - The inhibitory effects of curcumin and two tetrahydrocurcuminoids on tumor
      promoter-induced oxidative stress in vitro and in vivo were investigated.
      Curcumin, tetrahydrocurcumin (THC) and dihydroxytetrahydrocurcumin (DHTHC)
      exhibited significant inhibitory effects on 12-O-tetradecanoylphorbol-13-acetate
      (TPA)-induced O2-generation in differentiated HL-60 cells. The inhibitory
      activity of THC was weaker than that of curcumin. This tendency was the inverse
      of the results of previous studies on in vitro antioxidative activity against
      lipid peroxidation. The curcuminoids inhibited TPA-induced intracellular peroxide
      formation in differentiated HL-60 cells. THC exhibited much weaker inhibition of
      intracellular peroxide formation than curcumin, suggesting that this inhibition
      might be attributable to the inhibition of O2-generation. The inhibitory effects
      of curcuminoids on TPA-induced H2O2 formation in female ICR mouse skin were
      further examined using the double-TPA-application model. Each TPA application
      induces two distinct biochemical events, 1) recruitment of inflammatory cells to
      the inflammatory regions and 2) activation of oxidant-producing cells. Double
      pretreatment of mice with curcuminoids before each TPA treatment significantly
      suppressed double TPA application-induced H2O2 formation in the mouse skin.
      Coadministrations of curcumin with either first or second TPA treatment
      significantly inhibited H2O2 formation. In addition, THC tends to show weaker
      inhibitory activities than curcumin in bioassays related to tumor promotion,
      i.e., inhibition of tumor promoter-induced inflammation in mouse skin and Epstein
      Barr virus activation. These tendencies were parallel to those in the tumor
      suppressive potential of curcumin and THC in mouse skin, as previously reported.
      Thus, we concluded that curcuminoids significantly suppress TPA-induced oxidative
      stress via both interference with infiltration of leukocytes into the
      inflammatory regions and inhibition of their activation.

PMID- 9617341
TI  - Suppressive effect of irsogladine maleate on diethylnitrosamine-initiated and
      phenobarbital-promoted hepatocarcinogenesis in male F344 rats.
AB  - Modifying effects of irsogladine maleate (IRG) on diethylnitrosamine (DEN)
      induced hepatocarcinogenesis were examined in male F344 rats. Six-week-old rats
      were divided into 8 groups. Groups 1 through 4 were given a single i.p. injection
      of DEN (200 mg/kg body weight) at the start of the experiment, whereas groups 5
      through 8 received a single i.p. injection of saline as the vehicle treatment.
      Groups 1 and 8 were kept on the basal diet and distilled water throughout the
      experiment (36 weeks). Groups 2 and 7 were exposed to 500 ppm phenobarbital (PB)
      in the drinking water, starting one week after the carcinogen or vehicle
      treatment. Groups 3 and 5 were fed the diet mixed with 125 ppm IRG from one week
      after DEN or vehicle treatment. Groups 4 and 6 were given 125 ppm IRG-containing
      diet and drinking water with 500 ppm PB after the carcinogen or vehicle
      treatment. Liver neoplasms developed in groups 1 (1/15 rats, 7%) and 2 (14/14
      rats, 100%). However, no liver tumors were found in rats of groups 3 through 8.
      Incidence and average number of liver neoplasms in group 4 (0/14 rats, 0%) were
      less than those in group 2 (P < 0.0001). The number of glutathione S-transferase
      placental form (GST-P)-positive liver cell foci in group 3 or 4 was significantly
      smaller than that in the appropriate control (P < 0.01, P < 0.001, respectively).
      The average and unit areas of these foci in group 4 were also significantly
      smaller than those in group 2 (P < 0.001, P < 0.05, respectively). These results
      suggest that IRG could be a chemopreventive agent for rat liver carcinogenesis.

PMID- 9617342
TI  - Expression and localization of ornithine decarboxylase in reversible
      papillomatosis induced by uracil in rat bladder.
AB  - Direct mechanical irritation by uracil calculi formed following feeding of 3%
      uracil in the diet to male rats produces severe papillary hyperplasia
      (papillomatosis, which is reversible) of bladder epithelium. To evaluate the
      mechanism of the appearance of uracil-induced papillomatosis, we examined the
      changes of the enzyme activity and the localization of ornithine decarboxylase
      (ODC), as well as polyamine biosynthesis, and epithelial proliferation, that
      accompany the sequential bladder epithelial changes following administration and
      withdrawal of uracil. Moreover, expression of ODC mRNA was investigated using
      northern blotting and localization of ODC mRNA was demonstrated using in situ
      hybridization. ODC activity during uracil administration was maintained at a high
      level compared to that in normal epithelium, but sharply decreased after
      cessation of uracil treatment. The accumulation of ODC protein was observed in
      the proliferating bladder epithelium by immunohistochemical examination and
      western blotting analysis, and even after cessation of treatment, the protein
      binding to anti-ODC antibody remained mildly elevated. Sequential changes of
      proliferating cell nuclear antigen (PCNA)-positive cells in the epithelium during
      the development and disappearance of papillomatosis correlated with ODC activity.
      ODC mRNA was expressed strongly in the proliferating epithelium in rats treated
      with uracil and weakly in normal epithelium, in accordance with the location of
      ODC protein. Consequently, our data demonstrate that cell proliferation in the
      development of papillomatosis is closely associated with polyamine metabolism,
      and moreover suggest that ODC activity is up-regulated at a post-translational
      step.

PMID- 9617343
TI  - N-methyl-N-nitrosourea concentration-dependent, rather than total intake
      dependent, induction of adenocarcinomas in the glandular stomach of BALB/c mice.
AB  - The influence of the level of carcinogen exposure on histopathological types and
      cellular differentiation of the induced tumors was examined in 100 male BALB/c
      mice given N-methyl-N-nitrosourea (MNU) in their drinking water at 240 ppm on
      alternate weeks (total exposure: five weeks) (groups 1), at 120 ppm similarly
      (total exposure: ten weeks) (group 2), at 60 ppm for 20 weeks continuously (group
      3), or at 30 ppm for 40 weeks continuously (group 4). Forty-three differentiated
      and 17 undifferentiated type adenocarcinomas were induced. Glandular stomach
      carcinomas and undifferentiated type lesions were more common in mice treated
      with a high concentration of MNU for a short period than with a low concentration
      of MNU for a long period, even though total measured intake of MNU was smaller (P
      < 0.01). All the induced glandular stomach carcinomas, independent of the
      treatment schedule, consisted entirely of gastric phenotype cells. In conclusion,
      the induction of glandular stomach cancers and the proportion of undifferentiated
      type lesion depend not on the total quantity, but rather on the concentration of
      the carcinogen, while the phenotypic expression of tumor cells in not affected by
      the differences in the administration protocol.

PMID- 9617344
TI  - Piroxicam and acarbose as chemopreventive agents for spontaneous intestinal
      adenomas in APC gene 1309 knockout mice.
AB  - The use of nonsteroidal anti-inflammatory drugs has been suggested to have a
      chemopreventive effect against colon carcinoma, through the inhibition of
      cyclooxygenases 1 and 2, in patients with familial adenomatous polyposis and in
      animal models. Acarbose, an alpha-glycosidase inhibitor, may also be
      chemopreventive. In order to examine the effects of these drugs we employed APC
      gene knockout mice randomized into 3 groups, one for treatment with piroxicam
      (0.05% concentration in drinking water), one for acarbose (0.04% concentration in
      food) and another for the control. After 14 weeks of treatment, mice were killed
      for quantitation of gastric and intestinal adenomas. Tumor multiplicity in the
      whole gastrointestinal tract decreased from 33.89 +/- 13.07 tumors/mouse in the
      control group to 17.05 +/- 7 tumors/mouse in the piroxicam-treated group (P <
      0.001). The decrease in the acarbose-treated group (29.68 +/- 12.86 tumors/mouse)
      was not significant (P < 0.05). The number of tumors > or = 3 mm in diameter was
      also quantified in all gastrointestinal segments. The number of such tumors in
      the piroxicam group was decreased to 0.56 +/- 1.2 tumors/mouse from the control
      value of 3.78 +/- 1.17 tumors/mouse (P < 0.001), while in the acarbose-treated
      group the number decreased to 2.36 +/- 1.7 tumors/mouse (P < 0.01). Thus,
      piroxicam decreases the size and number of gastrointestinal adenomas in APC 1309
      knockout mice, while acarbose decreases only the size.

PMID- 9617345
TI  - Reduced invasive and metastatic potentials of KAI1-transfected melanoma cells.
AB  - KAI1 is a metastasis suppressor gene for human prostate cancer. To reveal the
      effect of KAI1 on the in vivo metastasis of tumors other than prostatic cancer,
      we transfected a human KAI1 cDNA into highly metastatic B16-BL6 murine melanoma
      cells and established stable transfectant clones with different expression levels
      of KAI1 message. The following results were obtained with the use of those
      transfectants. (1) Cell aggregation assay revealed a significantly enhanced
      Ca(2+)-independent aggregation of B16-BL6 cells by KAI1 cDNA transfection
      compared with mock transfectants (P < 0.01). (2) The in vivo phagokinetic
      activity and invasive ability of KAI1 transfectants were clearly decreased as
      compared with those of mock transfectants (P < 0.01). There was no significant
      effect of KAI1 expression on the in vitro or in vivo proliferation of B16-BL6
      cells. (3) Lung colony formation of intravenously injected KAI1 transfectants in
      nude mice was significantly reduced as compared with mock transfectants or
      parental B16-BL6 cells (P < 0.01). These data suggest that KAI1 expression gives
      rise to the suppression of invasive and metastatic potentials of B16-BL6 cells.

PMID- 9617346
TI  - Heterogeneity of p53 mutational status in esophageal squamous cell carcinoma.
AB  - In esophageal squamous cell carcinoma, p53 gene mutations have been analyzed for
      inter- or intra-patient heterogeneity but only a few studies have investigated
      intratumoral heterogeneity. We investigated this question within individual
      esophageal cancers, and also in their lymph-node metastases in 8 cases. Analyzing
      the p53 gene sequence by direct sequencing of polymerase chain reaction products,
      we found heterogeneity for p53 mutations in the pre-invasive area in 3 esophageal
      cancers. In all areas sampled in the invasive portion of each cancer, the p53
      mutational status was identical in a given tumor. In heterogeneous tumors, the
      invasive area showed one of the p53 mutations found in the pre-invasive area. In
      nodal metastases, the p53 mutation was identical to that in the invasive area of
      each primary tumor. These data suggest that the timing of p53 alteration is not
      as early as might have been expected, indicating that, in regard to p53 gene
      alteration, some esophageal cancers are composed of various subclones in the pre
      invasive stage with invasiveness developing in one of them, which becomes
      predominant through clonal selection.

PMID- 9617347
TI  - Novel point mutations and allele loss at the RET locus in sporadic medullary
      thyroid carcinomas.
AB  - Germline mutations in the RET proto-oncogene have been shown to be the underlying
      cause of multiple endocrine neoplasia type 2 (MEN 2A and 2B) and familial
      medullary thyroid carcinoma (FMTC). Some cases of sporadic medullary thyroid
      carcinoma (sporadic MTC) are reported to have specific codon 918, 883 and 768
      mutations of the RET gene in tumor tissues. We examined RET gene mutations in 40
      Japanese cases who had previously undergone surgery for sporadic MTC. DNA
      extracted from formalin-fixed tumor tissues and corresponding normal thyroid
      tissues or peripheral blood leukocytes was analyzed for mutations of exon 10, 11,
      13, 14 and 16 of the RET gene by DNA sequencing and by mutation-specific
      restriction enzyme analysis. Germline RET point mutations were found in six of 40
      cases (15%), cysteine residues at codon 618 in two, codon 634 in three and valine
      residue at codon 804 in one, and were newly identified as heritable MTC. Of the
      remaining 34 sporadic MTC cases, four (12%) had tumor-specific RET point
      mutations. Two were found in exon 16; one case showed an ATG to ACG (Met to Thr)
      mutation at codon 918, and the other showed two point mutations, ATG to ACG (Met
      to Thr) at codon 918 and GCA to GTA (Ala to Val) at codon 919 with loss of the
      wild-type allele, suggesting that both alleles at the RET locus were altered. The
      other two were found in exon 13; one case showed a CCG to TCG (Pro to Ser)
      mutation at codon 766 and the other showed a silent mutation, GTC to GTT (Val) at
      codon 778 with loss of the wild-type allele. There was no association of sporadic
      mutations with recurrence or prognosis in patients with sporadic MTC. The low
      rate of somatic RET mutation at codon 918 in our sporadic MTC suggests that as
      yet unknown factors may be involved. Genetic alterations in both alleles may have
      an important role in small fraction of sporadic MTCs.

PMID- 9617348
TI  - Clinicopathological criteria for multicentricity of hepatocellular carcinoma and
      risk factors for such carcinogenesis.
AB  - Multicentric occurrence is an important characteristic of hepatocellular
      carcinoma. We evaluated clinicopathological criteria for multicentric
      hepatocellular carcinoma and identified risk factors for such carcinogenesis.
      Subjects were 251 consecutive patients undergoing liver resection for
      hepatocellular carcinoma. One kind of multicentric hepatocellular carcinoma had
      at least one tumor consisting of well-differentiated hepatocellular carcinoma,
      together with moderately or poorly differentiated hepatocellular carcinoma
      located in a separate region. The other kind had an area of well-differentiated
      component around hepatocellular carcinoma with less differentiation in all
      occurrences. The outcome of patients with tumors classified in this way was
      studied. Univariate and multivariate analyses were done to identify risk factors
      for multicentric hepatocellular carcinoma. The cumulative survival rate was
      significantly higher in patients with multicentric hepatocellular carcinoma than
      in patients with hepatocellular carcinoma associated with intrahepatic
      metastasis. Analysis by Cox's proportional hazard model showed that
      multicentricity was not a factor in the outcome. The risk of multicentric
      occurrence increases with progression of chronic liver disease. Univariate
      analysis showed hepatitis C virus marker and hepatitis B core antibody to be risk
      factors. By multivariate analysis, the odds ratio for multicentric occurrence in
      patients infected with hepatitis C virus and with serum hepatitis B virus core
      antibody compared with patients without either hepatitis C virus or hepatitis B
      virus was 10.86. This ratio in patients with hepatitis C virus alone was 4.30.
      These criteria for multicentric hepatocellular carcinoma seem to be clinically
      useful. Hepatitis C virus infection with or without former infection by hepatitis
      B virus is a strong risk factor for multicentric hepatocarcinogenesis.

PMID- 9617349
TI  - Enhancement of anti-tumor activity of natural killer cells by BALL-1, a B cell
      lymphoma line.
AB  - The anti-tumor activity of human peripheral blood mononuclear cells (PBMC)
      against various tumor cell line cells (K562, Daudi, KMG-2, and KATOIII) was
      enhanced by coculture with irradiated BALL-1, but not with other irradiated B
      cell line cells (NALM-1, Namalwa, and Daudi). PBMC cocultured with BALL-1,
      however, failed to exhibit evident cytotoxicity against autologous concanavalin A
      induced lymphoblasts. The enhancement of the anti-tumor activity seemed not to be
      correlated with EBNA and HLA-DR expression on B cell line cells. Monoclonal
      antibodies (mAbs) against interleukin (IL)-2, interferon-gamma, IL-12, IL-15,
      tumor necrosis factor-alpha and lymphotoxin showed little or no suppression of
      the anti-tumor activity of PBMC treated with irradiated BALL-1. Furthermore, the
      culture supernatants of BALL-1 failed to enhance the anti-tumor activity of PBMC,
      suggesting no involvement of soluble factors in the induction of the anti-tumor
      activity. The anti-tumor activity of PBMC treated with BALL-1 was synergistically
      enhanced by an additional IL-2 stimulation. Periodate-lysine-paraformaldehyde
      fixed, but not ethanol- or acetone-fixed, BALL-1 could significantly enhance the
      anti-tumor activity. Furthermore, BALL-1-derived membrane fraction, but not that
      of Daudi, enhances the anti-tumor activity. It was thus suggested that some
      membrane glycoproteins on the cell surface of BALL-1 play a crucial role in the
      induction of the anti-tumor activity. By analysis using mAbs against human
      leukocytes, we found that depletion of CD11b, CD16, and CD56-positive cells
      resulted in decreased anti-tumor activity, suggesting that the main effector
      cells in the BALL-1-induced anti-tumor activity were natural killer (NK) cells.
      The present results thus raise the possibility that BALL-1, probably via membrane
      glycoproteins, modulates NK cell-mediated anti-tumor activity.

PMID- 9617350
TI  - Epitope blocking: positive and negative effects on the biodistribution of 125I
      labeled anti-Tac disulfide-stabilized Fv fragment of two antibodies against
      different epitopes of the circulating antigen.
AB  - Prior in vivo studies using the 125I-labeled anti-Tac disulfide-stabilized
      variable region fragment (125I-anti-Tac dsFv) of monoclonal antibody in the
      presence of the circulating soluble alpha subunit of the interleukin-2 receptor
      (sIL-2R alpha) have shown formation of complexes which interfere with
      biodistribution. In this study we evaluated the effects of preinjecting HuTac and
      7G7/B6, two immunoglobulin Gs (IgGs) that recognize different epitopes of sIL-2R
      alpha, on the biodistribution of 125I-anti-Tac dsFv in mice bearing SP2/Tac tumor
      xenografts, which produce sIL-2R alpha, or on nude mice injected with 500 ng of
      sIL-2R alpha. We also evaluated the biodistribution in mice of 125I-labeled sIL
      2R alpha injected alone or with HuTac and 7G7/B6. Injection of either HuTac or
      7G7/B6 resulted in complexes with the sIL-2R alpha in serum. Injection of HuTac
      before 125I-anti-Tac dsFv, in SP2/Tac tumor-bearing mice, resulted in faster
      clearance of the dsFv from the blood (7.6% ID/g at 30 min), compared to 23.2%
      ID/g for the no-antibody control; preinjection of 7G7/B6 prolonged the retention
      of 125I-anti-Tac dsFv to 35.3% ID/g, with more complexes in serum. In mice pre
      injected with 7G7/B6 the concentration of 125I-anti-Tac dsFv in tumor was lower
      (5.2 +/- 0.3% ID/g) than in mice preinjected with HuTac (7.9 +/- 1.2% ID/g) or in
      the control group (5.6 +/- 0.7% ID/g). In conclusion, while both IgGs formed
      complexes with sIL-2R alpha and prolonged its retention, preinjection of 7G7/B6
      was detrimental, because the increased circulating sIL-2R alpha still had the
      epitope recognized by the dsFv available for binding and neutralized the anti-Tac
      dsFv upon injection, whereas preinjection of HuTac blocked the epitope.

PMID- 9617351
TI  - Clotrimazole, an imidazole antimycotic, is a potent inhibitor of angiogenesis.
AB  - Clotrimazole, an imidazole antimycotic, interferes with the rise in cytosolic
      Ca2+ and inhibits cell proliferation in a reversible manner. Here we describe the
      effect of clotrimazole on vascular endothelial cells (ECs). Clotrimazole
      inhibited the proliferation of ECs stimulated with typical angiogenic growth
      factors; vascular endothelial growth factor and basic fibroblast growth factor
      (bFGF). This inhibitory effect of clotrimazole was dose-dependent and the maximal
      inhibition was observed at a concentration of 10 mM. We did not observe any
      increase in 51Cr release from ECs during treatment with 10 microM clotrimazole.
      Moreover, clotrimazole inhibited the basal and bFGF-stimulated migration of ECs.
      As clotrimazole inhibited two principle components of angiogenesis; the
      proliferation and migration of ECs, we examined whether clotrimazole inhibited
      angiogenesis. Tube formation by ECs in type 1 collagen gel was investigated, and
      clotrimazole was found to be significantly inhibitory. The inhibitory effect of
      clotrimazole on angiogenesis was further confirmed in an in vivo angiogenesis
      model of murine Matrigel plug assay. These results demonstrate that clotrimazole
      is a potent inhibitor of angiogenesis.

PMID- 9617352
TI  - Antitumor effect sonodynamically induced by focused ultrasound in combination
      with Ga-porphyrin complex.
AB  - The antitumor effect of focused ultrasound in combination with Ga-porphyrin
      complex, 7,12-bis(1-decyloxyethyl)-Ga(III)-3,8,13,17 tetramethylporphyrin-2,18
      dipropionyl diaspartic acid (ATX-70), on the growth of experimental murine tumors
      was examined. Walker 256 tumors implanted in rat kidneys were exposed in a
      progressive wave field for 5 min to focused ultrasound at 500 kHz with the second
      harmonic (at 1 MHz) superimposed after administration of ATX-70 to the rats. A
      significant antitumor effect was obtained at a focal-spot average acoustic
      intensity of 12 W/cm2 or higher with an ATX-70 dose of not less than 2.5 mg/kg.
      When the acoustic intensity was 8 W/cm2 or lower, no significant effect was
      observed even at an ATX-70 dose of 2.5 mg/kg. Also when the ATX-70 dose was 1.0
      mg/kg or lower, no significant effect was observed even at a focal-spot average
      acoustic intensity of 40 W/cm2.

PMID- 9617353
TI  - In vivo adenovirus-mediated prodrug gene therapy for carcinoembryonic antigen
      producing pancreatic cancer.
AB  - In gene therapy for malignancy, the herpes simplex virus thymidine kinase (HSVtk)
      ganciclovir (GCV) system has been widely used. For pancreatic cancer targeting,
      we estimated the therapeutic efficacy of gene transduction by an adenovirus
      carrying HSVtk gene under the control of a carcinoembryonic antigen (CEA)
      promoter (AdCEAtk) followed by systemic administration of GCV. Four cell lines,
      CEA-producing Su.86.86. BxPC-3 (pancreatic cancer cells), MKN45 (gastric cancer
      cells) and CEA-nonproducing HeLa, were used for analysis of GCV sensitivity
      induced by adenoviral gene transduction. To evaluate the therapeutic efficacy of
      AdCEAtk and GCV administration in human CEA-positive pancreatic cancer in vivo, a
      subcutaneously implanted tumor-bearing nude mouse model was used. When the HSVtk
      gene was transduced with a ubiquitous promoter into these cells, increase of the
      GCV sensitivity was independent of CEA-production. In contrast, when the cells
      were transduced with a CEA promoter, the cell-killing effect of GCV was increased
      in only CEA-producing cells. For in vivo analysis, AdCEAtk was delivered into
      subcutaneously established tumors of Su.86.86 cells. Immunohistochemical staining
      of the tumor showed that HSVtk protein was expressed only in tumor cells, and
      tumor growth was markedly suppressed by administration of GCV. These results
      suggest that the adenovirus-mediated transfer of HSVtk gene with CEA promoter
      specifically increases the GCV sensitivity of CEA-producing pancreatic cancer
      cells in vitro and in vivo. This strategy may provide a useful tool for treating
      pancreatic cancer, especially CEA-producing tumor cells.

PMID- 9617355
TI  - [The moose test and the medical product law].

PMID- 9617354
TI  - Intracellular hyperthermia for cancer using magnetite cationic liposomes: an in
      vivo study.
AB  - The effect of hyperthermia on solid glioma tissue formed subcutaneously in the
      left femoral region of female F344 rats was investigated. Magnetite cationic
      liposomes (MCLs), which have a positive surface charge, were used as heating
      mediators for intracellular hyperthermia. MCLs were injected into the solid
      tumors, which were then subjected to irradiation by an alternating magnetic field
      (118 kHz, 384 Oe). The rats were divided into four groups, which received no
      irradiation (control: group I), or irradiation for 30 min given once (group II),
      twice (group III) or three times (group IV), and the hyperthermic effect on tumor
      growth was evaluated. Complete tumor regression was observed in 87.5% of the rats
      in group IV. In the other groups, tumors completely regressed in 20 and 60% of
      the rats in groups II and III, respectively. Histological observations showed
      that in group I tumors, MCLs were localized only around the point where they were
      injected, while in group II tumors they were a little more dispersed. In the
      cases of group III and IV tumors, however, the distribution of the MCLs was found
      to be widespread, and necrotic cells were observed throughout almost the entire
      tumor tissue. The high percentage of complete regression of group IV is
      considered to be due to this wide distribution of the MCLs. Furthermore, the
      treated rats showed no severe side-effects. These results suggest that our
      magnetic particles are potentially effective tools for the treatment of solid
      tumors.

PMID- 9617356
TI  - [Infrapopliteal angioplasty: a forgotten region?].
AB  - Although percutaneous transluminal angioplasty (PTA) has become established as an
      endovascular technique--in the more strict sense as a balloon dilatation but
      being increasingly supplemented by stent implantations--for many vascular
      regions, reports on infrapopliteal angioplasties are rather scarce. With the
      development of hydrophilically coated guide wires, improved catheter materials,
      and dedicated balloon catheters for infrapopliteal use, dilatation treatments
      distal of the popliteal artery are now standard procedures. Major advances in
      peri-interventional drug management have also made their contribution. The
      initial technical and clinical results obtained are excellent. For the majority
      of the patients, the main concern is for limb salvage. In this context,
      infrapopliteal PTA also achieves satisfactory results. However, the long-term
      results must still be considered as unsatisfactory since recurrences are frequent
      and require repeat interventions. Therefore new therapeutic strategies are
      required that can reduce re-stenoses especially in this peripheral vascular
      segment.

PMID- 9617357
TI  - [Differential diagnosis of erosive osteochondrosis and bacterial spondylitis:
      magnetic resonance tomography (MRT)].
AB  - PURPOSE: To evaluate retrospectively criteria in the differential diagnosis of
      erosive osteochondrosis (EO) and infectious spondylitis (IS) on the basis of MRI.
      METHODS: T1-weighted sagittal images before and after Gd-DTPA application, T2
      weighted TSE or T-STIR images of 23 patients with proven 15 and 41 patients with
      EO were evaluated. Criteria for this evaluation were morphology and extension of
      bone marrow edema, visibility of the low-intensity vertebral endplate, contrast
      enhancement and signal intensity in the disc space on T2-weighted and T-STIR
      images. RESULTS: Bone marrow edema was more extensive in IS than in EO. The mean
      rated value for bone marrow edema on a four-level scale (0-3) was for IS 2.91 (+/
      0.29), for EO 1.32 (+/- 0.76, p < 0.001). In 37/41 cases of EO and in 22/23
      cases of IS Gd-DTPA enhancement was found in the disc space (n.s.). In EO the low
      intensity endplate was visible in all parts in 36/41 cases (87.8%) on T1-weighted
      images, in IS not in a single case (0%). On T2-weighted or STIR images signal
      intensity of the discs was decreased in 82.1% of EO, 82.6% of segments in IS had
      water-equivalent signal intensity (p < 0.001). CONCLUSION: If all the criteria
      are taken into consideration differential diagnosis of EO and IS on the basis of
      MRI findings is possible.

PMID- 9617358
TI  - [Correlation of MRI and histopathological findings in inflammatory skin
      diseases].
AB  - PURPOSE: Can spatial and contrast resolution be achieved with currently available
      MR devices for the successful assessment of inflammatory diseases of the skin?
      METHOD: High resolution MRI was performed in 20 patients with non-malignant
      diseases of the dermis and subcutis. The skin biopsies subsequent to the MR
      examinations were indicated for clinical reasons. The MR examinations were done
      in the location of later performed skin biopsies using a 1.0 Tesla system
      (Gyroscan T10 NT, Philips, Best, the Netherlands) and a surface coil of 7.5 cm
      inner diameter. Conventional spin-echo (SE-Sequenz)- and gradient-echo (GRE)
      sequences were optimised to obtain maximum spatial resolution with a sufficient
      signal-to-noise ratio within a tolerable examination time. MR visualisation of
      histopathology was assessed by four readers using a questionnaire. RESULTS: In 15
      of 20 cases, high resolution MRI allowed a correct classification of the
      visualised dermal and subcutaneous patterns, in accordance with the histological
      work-up of the corresponding specimen. Due to the still only suboptimal spatial
      and contrast resolution the structure of the epidermis could not be assessed
      adequately. Determination of contrast enhancement or non-enhancement after
      administration of intravenous contrast agent provided information on the degree
      of tissue perfusion in 19 patients, which complemented the morphological
      assessment. CONCLUSION: High resolution MRI allows to identify non-invasively
      histological main patterns of inflammatory skin diseases. However, final
      diagnosis often depends on higher microscopic resolution and special staining.

PMID- 9617359
TI  - [MRI with supermagnetic iron particles versus double-spiral CT in identification
      of malignant liver lesions].
AB  - PURPOSE: The purpose of this study was to evaluate the efficacy of MRI with
      superparamagnetic iron oxide (SPIO) and double-spiral CT in the detection of
      liver metastases and hepatocellular carcinoma. METHODS: 38 patients with a total
      of 144 malignant hepatic lesions underwent CT and MRI. A panel of experts defined
      the gold standard. Five experienced judges performed independently blinded
      evaluation of the number of detectable lesions. Multifactorial variance analysis
      was used to determine the statistical significance. RESULTS: SPIO-MRI shows the
      highest rate of detection and is significantly superior to native MRI and native
      CT. The highest rate of detection by CT is shown in the portal-venous phase of
      contrast; nevertheless, the rate is significantly inferior to SPIO-MRI. In
      general, the native phases of CT and MRI are significantly inferior to the
      contrast phases of both. SPIO-MRI shows a higher rate of false positive findings.
      CONCLUSION: The time-consuming and cost-intensive SPIO-MRI significantly
      increases the rate of detectability for malignant liver lesions compared with
      double-spiral CT but it also increases the rate of false positive findings.

PMID- 9617360
TI  - [Color-coded signal-enhanced duplex ultrasonography of space-occupying
      intramammary processes].
AB  - PURPOSE: Prospective comparison of plain and signal-enhanced frequency and
      amplitude-modulated colour Doppler ultrasound of intramammary tumours to evaluate
      new criteria for diagnostic analysis. METHODS: Frequency and amplitude-modulated
      colour Doppler examination with qualitative and quantitative analysis of 80
      potentially malignant intramammary lesions were performed before and after
      application of d-galactose. RESULTS: Signal-enhanced sonography revealed a
      typical vessel morphology of primary and recurrent breast cancer facilitating
      differential diagnosis. In 18 (frequency modulated US) or 16 (amplitude modulated
      US) of 51 carcinomas, the typical malignant vascularisation structure was
      sufficiently visible only after application of the signal enhancing agent. In 50%
      of the fibroadenomas, Doppler analysis of the vessels was possible only after
      application of d-galactose. CONCLUSION: The application of d-galactose provides
      additional criteria for the differential diagnosis of breast lesions due to
      improved visualisation of the vascularisation structure.

PMID- 9617361
TI  - [Imaging of the normal skeletal system with 18F Na-PET compared with conventional
      skeletal scintigraphy using Tc99m-MDP].
AB  - PURPOSE: We evaluated the feasibility of 18 Fluoride Positron Emission Tomography
      (18F-PET), investigated the characteristics appearance of bony structures, and
      compared the quality of 18F-PET images with conventional bone scans (BS). METHOD:
      18F-PET scans were performed in 59 patients additional to conventional bone
      scintigraphy. RESULTS: Even very small details in the spine like the spinous and
      transverse processes were clearly visible with 18F-PET. Only half of these
      structures were visualised with BS. When visualising the vertebral bodies of the
      first rib from the clavicles and the twelfth rib from the kidneys, we arrived at
      similar results. Hot spots in the skull or at the manubriosternal joint were
      observed in 29% of the patients without any evidence of trauma, degeneration or
      metastasis. CONCLUSION: 18F-PET shows more details of the skeleton compared to
      BS. Some hot spots not occurring with BS must be regarded as physiological.

PMID- 9617362
TI  - [Computerized tomography and F-18-FDG positron emission tomography in staging of
      malignant lymphomas: a comparison].
AB  - PURPOSE: To determine the value of F-18-FDG-positron emission tomography (FDG
      PET) compared with computed tomography (CT) in the staging of malignant
      lymphomas. MATERIAL AND METHOD: 50 patients with biopsy-proven lymphoma were
      studied with FDG-PET and CT. The results in initial, posttherapeutic and staging
      of recurrence were compared. RESULTS: 37 of 65 FDG-PET were identical with CT. 28
      studies showed differences. 14 post-therapeutically and one of the initial
      studies led to downstaging by FDG-PET were as upstaging resulted in one case of
      initial staging. In two cases false positive pulmonary FDG accumulations caused
      an upstaging. CONCLUSION: FDG-PET was at least comparable to CT in recording the
      extension of a newly diagnosed lymphoma, or its recurrence. Upstaging according
      to FDG-PET occurred only once in initial staging. FDG-PET plays its most
      important role in the evaluation of residual mass in CT after therapy by
      accumulating FDG in viable tumour rather than in fibrotic tissue. 14 cases of
      downstaging according to FDG-PET resulted.

PMID- 9617363
TI  - [Magnetic resonance imaging of of the right extraocular muscle paths in healthy
      persons and in patients with high myopia].
AB  - PURPOSE: To investigate the paths of the rectus extraocular muscles (EOMs) in
      patients with high axial myopia, using high-resolution magnetic resonance imaging
      (MRI). METHODS: Coronal MR images (T1 weighting) of the orbit were obtained with
      controlled gaze. Positions of recti EOMs were measured digitally in the middle of
      the orbit, using the NIH-image analysis software. Orbits of three different
      patient groups were analysed. Group 1 (n = 14 orbits): Patients with high axial
      myopia and restrictive eye motility. Group 2 (n = 8 orbits) subjects with high
      axial myopia and normal eye motility. Controls (n = 11 orbits) with normal eye
      motility and no refractive error. RESULTS: In comparison to the controls,
      patients with high axial myopia were found to have significant misplacement of
      the recti EOMs. Thus in group 1 (group 2 within brackets) the lateral rectus
      muscle (LR) was misplaced 2.9 (1.4) mm into the lower temporal quadrant p < 0.001
      (p = 0.07). The course of the superior rectus muscle (SR) was shifted 1.5 (1.5)
      mm medially p = 0.02 (p = 0.03) and the path of the inferior rectus muscle (IR)
      1.3 (1.3) mm medially p = 0.06 (p = 0.06). The medial rectus muscle (MR) showed a
      1.3 (1.2) mm downward mislocation p = 0.01 (p = 0.07). CONCLUSIONS: In patients
      with high axial myopia (group 1 and group 2) misplacement of all rectus EOMs
      could be demonstrated by high resolution MRI with controlled gaze. All patients
      showed an approximately equal amount of MR, SR and IR mislocation. However,
      misplacement of the LR was significantly greater in patients with high myopia and
      restrictive eye motility (group 1) than in those without restrictive ocular
      motility (group 2), p = 0.03. We therefore assume that LR downward mislocation is
      a major determinant for restrictive eye motility in high myopia.

PMID- 9617364
TI  - [Dosage measurements in spiral CT examinations of the head and neck region].
AB  - PURPOSE: In view of the increasing frequency of computed tomographic examinations
      the organ doses of the thyroid gland and the eye lenses in spiral CT examinations
      of the head and neck should be determined. MATERIAL AND METHODS: Standard CT
      examinations of the neck, the paranasal sinuses in axial and coronal sections,
      and the mandibula were simulated by help of an Alderson-Rando phantom. Dose
      measurements were performed as well in 28 patients. The examinations were carried
      out in spiral mode ("Somatom AR.SP", "Picker PQ 2000", and "Toshiba Xpress SX")
      and conventional single slice technique ("Somatom Plus"). Three LiF-TLD were
      placed on each eyelid and three on the thyroid. RESULTS: With direct exposure to
      the x-ray-beam the organ doses did not exceed 64 mGy. When exposed by scatter
      radiation only, doses may be reduced by a factor of up to 10. The measurements in
      28 patients showed similar results. CONCLUSIONS: The organ doses in spiral CT
      correspond with data known from conventional CT.

PMID- 9617365
TI  - [Cardiac MR flowmetry: experimental validation and results in patients with
      operated heart defects].
AB  - PURPOSE: A flow-sensitive MR sequence (phase-contrast technique) was evaluated in
      phantom studies with regard to factors influencing measurements and correctness
      of results. The sequence was additionally used for functional evaluation of
      operated congenital heart disease. METHODS: Pulsatile and constant flow were
      produced with the help of a phantom. Influence of angulation, range and vessel
      bending was evaluated. An examination protocol was developed from the results. 35
      patients with surgically repaired congenital heart disease or without repair were
      examined. RESULTS: A range preset below the actual flow velocity as well as
      angulation of more than 20 degrees were isolated as main pitfalls in MR
      flowmetry. In addition to morphological MR findings flow measurements were
      possible in 11 patients at vessel sites which were not or not completely suited
      for examination by Doppler ultrasound. CONCLUSION: The evaluated phase-contrast
      technique allows for fast and reliable flow quantification if the influences
      identified in phantom studies are considered.

PMID- 9617366
TI  - [Value of dynamic MRI in the diagnosis of hypophyseal microadenomas].
AB  - PURPOSE: To evaluate dynamic MR imaging of the pituitary gland. MATERIAL AND
      METHODS: 19 patients with suspected mass lesions of the pituitary gland were
      examined at 1.5 Tesla with dynamic and standard MRI using a Turbo-FLASH sequence
      (1 image/s for 40 s). RESULTS: In 13/19 patients microadenomas were detected. One
      of the 13 microadenomas was detected using dynamic imaging and was not seen on
      standard MRI. The remaining 12 microadenomas were diagnosed with standard MRI.
      CONCLUSION: Dynamic imaging of the pituitary gland is a time-consuming and costly
      diagnostic technique. If laboratory results suggest the presence of a
      microadenoma and conventional MRI is unable to localise it, dynamic imaging
      should be performed.

PMID- 9617367
TI  - [Improved diagnosis of early cerebral infarct by the combined use of diffusion
      and perfusion].
AB  - PURPOSE: To evaluate the feasibility and the diagnostic efficacy of multislice
      diffusion-weighted and perfusion imaging in addition to FLAIR-TSE, T2w-GraSE and
      MR-angiography in the diagnosis of acute stroke. METHODS: 18 patients with acute
      stroke were examined at 1.5 Tesla (Gyroscan ACS-NT, Philips Medical Systems)
      within 6 (n = 9) and 6-48 (n = 9) hours, respectively, and followed at regular
      intervals. For diffusion imaging we used a multislice multishot EPI-SE sequence
      with navigator echo correction and cardiac gating. Perfusion imaging was done by
      means of a FFE-EPI sequence after bolus injection of Gd-DTPA. RESULTS: The
      diagnostic value of diffusion-weighted and perfusion imaging was significantly
      higher compared with FLAIR-TSE (p = 0.0023) and GraSE (p = 0.0012) during the
      first 6 hours. With FLAIR-TSE and GraSE first pathologic changes were seen after
      4 hours. We detected perfusion deficit (rCBV < 10%) and a corresponding drop of
      the ADC in all infarcts larger than 1 cm in diameter. Within the area of low rCBV
      the combined analysis of diffusion and perfusion imaging allows to identify an
      infarct region with characteristics of a penumbra and one with characteristics of
      the infarct core. TTP was increased in the surrounding tissue. However, parts of
      this area were rarely included in the infarct. The final extension of the
      untreated infarct, as revealed by computed tomography, corresponded well to the
      perfusion deficit. CONCLUSIONS: Early ischaemic cerebral infarcts can be
      diagnosed with diffusion and perfusion imaging before pathological changes are
      visualized with other imaging modalities. The combined use may allow to
      distinguish the infarct core from surrounding, potentially salvageable tissue.

PMID- 9617368
TI  - [Computerized tomography and magnetic resonance imaging findings in central
      neurocytoma].
AB  - PURPOSE: Analysis of our CT and MRI findings in patients with central
      neurocytomas in comparison with the relevant literature. MATERIALS AND METHODS: 5
      patients were examined by CT and MRI. A retrospective analysis of the
      histologically confirmed tumors of our patient group and date from the literature
      was performed under the following criteria: 1. topography, 2. extent, 3. contrast
      medium behavior, 4. calcifications, 5. presence of intramural cysts, and 6.
      vascularization. These properties were evaluated according to a 5 point scale.
      RESULTS: All tumors originated in the roof of a lateral ventricles with
      participation of the pellucid septum and extended intraventricularly (5/5),
      showed cystic components (5/5), and took up contrast medium (5/5). Contrast
      medium uptake was visible in both CT and MRI. In contrast, only three of the 5
      tumors revealed calcifications (3/5) and these were better visible in CT than in
      MRI, no pathological vessels were detected. Because of its multi-planar
      representations and better soft-tissue contrast, MRI was superior to CT for the
      exact determination of origin and position of the tumors. The small cystic,
      inhomogenous appearance in T2-weighted images was considered to be an especially
      typical feature. CONCLUSIONS: The typical appearance of central neurocytomas in
      CT and MRI provides information for the differential diagnosis from other
      intraventricular tumors. The definitive diagnosis is provided by
      neuropathological evaluation.

PMID- 9617369
TI  - [Experimental evaluation of superparamagnetic iron oxide particles in pulmonary
      MR angiography].
AB  - PURPOSE: Initial experimental results of contrast-enhanced pulmonary MR
      angiography using the new superparamagnetic iron oxide blood pool agent FeO-BPA.
      METHOD: Pulmonary MRA was performed in 7 domestic pigs using a cardiac-triggered
      coronal T1-weighted FFE-Sequence before and up to 90 minutes after contrast
      injection obtained on a 1.5 T magnet with a standard gradient equipment. A dose
      of 4 mg Fe/kg bodyweight was used for MRA. The images were qualitatively assessed
      and compared with X-ray i.v.-DSA. RESULTS: The injection of FeO-BPA allows the
      acquisition of unsaturated in-plane images of the pulmonary vascular tree down to
      the first order subsegmental branches including vessel diameters of approximately
      1.5 mm. In the normal non-occluded vasculature, no signal void is seen in the TE
      range of 2.8-5.5 ms secondary to exceeding susceptibility effects which are
      caused by the iron oxide accumulation. Even 90 minutes after injection of FeO
      BPA, assessment of the pulmonary vasculature is still satisfactory. CONCLUSIONS:
      In the animal experiment, the use of the blood pool agent FeO-BPA provides
      detailed pulmonary angiograms even on a magnet with a conventional gradient
      system. The major advantage is the comfortable diagnostic window of > 1.5 hours
      which also portends its utility for future MR-guided pulmonary interventions.

PMID- 9617370
TI  - [Percutaneous therapy of occlusions of calf arteries with newly developed
      hydrodynamic thrombectomy catheter, Angiojet LF140].
AB  - PURPOSE: To evaluate the rheolytic thrombectomy catheter Angiojet LF140 (RTC) for
      treatment of calf artery occlusions. PATIENT AND METHOD: A 47-year-old male
      patient with an 8 cm measuring occlusion of the femoropopliteal and all calf
      vessels, suffering from limb threatening ischemia for 21 days, was treated with
      hydrodynamic thrombectomy (RT) using the modified RTC LF140. RESULTS: Most of the
      occluded segments could be successfully recanalized with the RTC. 450 ml of
      heparinized saline were injected. Parts of the tibial posterior artery and the
      fibular artery remained occluded. Additional long-term fibrinolysis therapy was
      administered (24 h), until all lower limb arteries were completely recanalized
      (+3 according to Rutherford). CONCLUSION: The modified RTK LF140 allows the
      treatment of acute thrombotic occlusions, even small caliber vessels. The device
      fails to remove organized and walladherent thrombus.

PMID- 9617371
TI  - [Gastric carcinoid].

PMID- 9617372
TI  - [High-resolution computerized tomography of the lung in alveolo-septal
      amyloidosis].

PMID- 9617373
TI  - [Radiological findings in intracerebral tuberculoma].

PMID- 9617374
TI  - [CT and MRI in pronounced dysplastic cranial changes in the framework of McCune
      Albright syndrome].

PMID- 9617375
TI  - [Stress fracture of the tibia in an infant. Value of diagnostic imaging].

PMID- 9617376
TI  - [Computerized tomography in atlanto-axial rotatory fixation in childhood].

PMID- 9617377
TI  - [Research on antiemetics: an Italian model of success].
AB  - At the beginning of the 80's the Italian Group for Clinical Research (G.O.I.R.C.)
      identified chemotherapy-induced nausea and vomiting as one of the most
      distressing adverse events, and decided to plan and execute clinical trials on
      antiemetics in order to reduce this negative impact on patients. Therefore, some
      consecutive double-blind randomized trials were conducted on cisplatin-treated
      patients. The first was a dose-finding study on four different high-doses of
      domperidone, followed by a study comparing two different high-doses of
      metoclopramide, and a study comparing the addition of a corticosteroid to high
      dose metoclopramide with respect to metoclopramide alone. Finally, a study
      demonstrating that a combination of a higher dose of metoclopramide (3 mg/kg x 2)
      plus dexamethasone and diphenhydramine was significantly superior with respect to
      a lower dose of metoclopramide (1 mg/kg x 4) combined with methylprednisolone was
      carried out. With the introduction of the 5-HT3 receptor antagonists the interest
      for antiemetic therapy increased and other Italian gynecological and medical
      oncology centres became involved in the antiemetic research. The Italian Group
      for Antiemetic Research was formed in 90's and its first study demonstrated the
      superiority of a combination of a 5-HT3 receptor antagonist plus dexamethasone
      with respect to the standard three drug combination of high doses of
      metoclopramide in the prevention of cisplatin-induced acute emesis. In the
      following years, the Group contributed to the identification of the best
      antiemetic prophylaxis for acute emesis induced by moderately emetogenic
      chemotherapy, and for delayed emesis induced by cisplatin. Also a drug
      utilization review on antiemetics in clinical practice has recently been carried
      out. Today, the interest of the Group is concentrated in studying the optimal
      antiemetic prophylaxis for delayed emesis induced by moderately emetogenic
      chemotherapy. The rules always followed by the Italian Group for Antiemetic
      Research are: --complete independence of judgement on the efficacy and the
      tolerability of antiemetic drugs from the pharmaceutical companies; --priority of
      ethical problems in designing clinical trials; --strict adherence to the
      methodological problems of antiemetic research and--complete autonomy concerning
      the study planned, the data computerization and the data elaboration. In the last
      twelve years approximately 70 Italian centres have enrolled their patients into
      the studies of the Italian Group for Antiemetic Research.

PMID- 9617378
TI  - [Supportive therapy in oncology].
AB  - The current trend towards a more intensive cancer treatment is possible thanks to
      the availability of a really important and effective supportive care. It is our
      opinion that it would be essential for the junior staff in oncology, for the
      practitioners, but also for the knowledge of anyone contributing in different
      ways to give the cancer treatment, to have reference points to give also the best
      supportive care. With this aim we thought to start a study, in Italy, to
      investigate, first, which is the supportive care used in the most common acute
      toxicities during or immediately after cancer therapy. We decided to begin with a
      survey addressed to hematologists, medical oncologists, radiotherapists; 105
      centers were contacted. In order to have a high number of people able to answer
      to different clinical questions we decided to use Internet to communicate with
      participating centers without moving people. The final goal of the project is to
      formulate guidelines in supportive care, but also to promote the use of Internet
      as much as possible in the medical world with the aim to make easier every kind
      of communication and exchange of information.

PMID- 9617379
TI  - [Gastroprotection in cancer patients: rational approach, pharmacologic role of
      antisecretory agents and eventual ulterior prospectives in oncology].
AB  - In view of the large number of cancer patients treated with FANS and/or
      corticosteroids for long periods of time. Authors discuss how the use of
      antisecretory drugs for gastroprotection has become common practice in spite of
      the lack of clear scientific evidence. The paper analyses the principal
      mechanisms of gastrotoxicity of FANS, essentially associated with the inhibition
      of prostaglandins and consequent reduction of the secretion of mucous and
      bicarbonate. It also discusses the numerous controlled trials evaluating the
      efficacy of ranitidine for gastroprotection versus placebo and versus the
      analogous synthetic substance, misoprostole, derived from prostaglandin E1. This
      analysis shows that misoprostole provides significant protection against both
      gastric and duodenal ulcers, whilst the antisecretory drug protects only against
      localised duodenal ulcer. The conclusion is that optimum protection against FANS
      is provided by misoprostole. In any case more than 30% of patients are destined
      to develop ulcerous or minor lesions for which treatment with antisecretory drugs
      is correct. After analysis of the available literature on the gastrotoxicity of
      corticosteroids, it is clear that this risk is real only for a small sub
      population of patients (treated in dual therapy with FANS, for long periods, with
      high doses or in presence of ulcer anamnesis). It is not known in these cases
      whether prophylactic treatment is suitable, nor which would be the best
      prophylactic treatment. In other cases the problem does not arise since the
      number of patients developing ulcers is similar with corticosteroids treatment or
      with placebo. Some further interesting features of ranitidine compared to
      cimetidine (its better pharmacological profile due to the lack of side effects,
      lack of medullary depression, lack of interference with the immunological system,
      lack of antiandrogen effects) are also discussed. Particularly interesting is the
      lack of interference with cyclophosphamide metabolism, such interference having
      shown for cimetidine. Studies involving ranitidine treatment in association with
      interleukin-2 for renal carcinoma and metastatic melanoma are also of interest
      although no statistically significant results are available as yet.

PMID- 9617380
TI  - [The impact of cancer on the healing status of patients].
AB  - The peculiar characteristics of the Italian neoplastic patients, as far as their
      knowledge concerning the disease (information, prognosis, therapeutic options,
      etc) and the different cultural, environmental and health realities, place
      different problems on the routine application of the quality of life
      questionnaires which were constructed and edited in North European or North
      American Countries, even if correctly translated and validated in Italy. The
      QVonc (Quality of Life in Oncology) Project started five years ago from the
      common interest of medical oncologists who felt the need to make a careful study
      on some aspects regarding the evaluation of Italian patient's quality of life. A
      multidisciplinary working group, comprehensive of statisticians, epidemiologists,
      psychologists, nurses and methodologists, was then put together. During the last
      three years the Group produced a deep analysis of the different aspects and
      determinants of the italian patient's quality of life, mainly about their disease
      and medical environment perception. A prospective research was started in 1995
      with the aims of identifying the contents of quality of life, using a sample of
      cancer patients as "experts" and of measuring the relevance of selected contents
      in different subgroups of patients. In the first study the quality of life
      dimensions were analysed as perceived from 248 neoplastic patients, uniformely
      and randomly distributed for pathology and place of residence in Italy, through
      an open questionnaire and interviews conducted by our psychologists. Some
      peculiar aspects of the quality of life perception in italian patients were
      evidenced: relationship with the family, with the medical team and health
      facilities, economic problems and occupational difficulties. The study confirmed
      that the information on the contents of quality of life can be derived only
      studying people suffering the specific disease and cast a doubt on the available
      QL instruments currently used. The second study evaluated the quality of life
      perception in 6939 consecutive cancer patients referred in the second week of
      July 1996 to 79 Italian medical oncology/radiotherapy institutions. Patients were
      asked to fill out a questionnaire concerning the importance of 46 domains of QL,
      each one scored on 4 levels (not at all, a little, much and very much). Domains
      were derived from a previous content analysis of 268 pts answers to 4 questions
      related to their own QL: "in your experience, what is QL?", "what is a bad QL?",
      "what is a good QL?", "Did the diagnosis and treatment received modify your QL?".
      6939 patients entered the study; of these, 820 (11.8%) did not fill out the
      questionnaire due to various reasons. Among the 6,119 evaluable pts, the most
      frequent cancers were: breast (2,328), colo-rectal (968), lung (517), lymphoma
      (351), gastric (225). The most frequently chosen domains (much or very much) were
      related to health facilities or communication between patient-physician/nurse.
      Family relationship and general well being were also found important, while from
      the negative perspective the presence of the disease and the related anxiety were
      the most relevant problems. In conclusion, when choosing or constructing QL
      instruments, at least for Italian cancer pts, factors such as health facilities
      and pt--physician/nurse relationship should be more adequately considered. Most
      currently used QL questionnaires are probably lacking in this regard.

PMID- 9617381
TI  - Quantitation of the extracellular domain of epidermal growth factor receptor in
      the plasma of dioxin-exposed individuals.
AB  - Animal models suggest that dioxins have a negative effect on the level of
      expression of the epidermal growth factor receptor in cells. In vivo the level of
      expression in tissue of the epidermal growth factor receptor can be monitored by
      assaying for the extracellular domain in blood using an enzyme linked
      immunosorbent assay. We have determined the levels of the extracellular domain of
      the epidermal growth factor receptor in the plasma of 30 individuals: 10 with
      high blood dioxin levels (TEQ range = 318-673 ppt), 10 with medium blood dioxin
      levels (TEQ range = 16-60 ppt), and 10 with low background blood dioxin levels
      (TEQ range = 3-10 ppt). The levels of the epidermal growth factor receptor
      extracellular domain were lower in the high blood dioxin group (mean +/- SD = 45
      +/- 26 fmol/ml) and the medium blood dioxin group (mean +/- SD = 41 +/- 23
      fmol/ml) compared with the low blood dioxin group (mean +/- SD = 73 +/- 43
      fmol/ml). These results suggest that the extracellular domain of the epidermal
      growth factor receptor may be a marker of the biological effect of dioxin
      exposure.

PMID- 9617382
TI  - Occupational exposure to estrogenic chemicals and the occurrence of breast
      cancer: an exploratory analysis.
AB  - BACKGROUND: We conducted a population-based case-control study to describe the
      relationship between occupational exposure to estrogenic chemicals and the
      occurrence of breast cancer in Cape Cod, Massachusetts. METHODS: Incident cases
      of breast cancer (n = 261) diagnosed from 1983 through 1986 and controls (n =
      753) were interviewed to gather information on breast cancer risk factors and all
      full-time jobs held since age 18. Blinded exposure assessments were employed
      using the data from the NIOSH National Occupational Exposure Survey, chemical
      production and usage information, and the expert judgement of a certified
      industrial hygienist. RESULTS: Overall, 29.5% of cases and 32.5% of controls had
      probable occupational exposure to one or more xenoestrogens. Probable exposure to
      nonylphenol (21.5% of cases, 21.4% of controls), butyl benzyl phthalate (10.0% of
      cases, 13.2% of controls), BHA (7.3% of cases, 9.6% of controls), bisphenol A
      (9.6% of cases, 11.6% of controls), and 4-tert-butylphenol (2.7% of cases and
      5.3% of controls) were relatively commons, while probable exposure to the other
      xenestrogens was rare. Only PCBs and 4-octylphenol were associated with moderate
      increase in the odds of breast cancer (PCBs: 5 exposed cases and 6 exposed
      controls, adjust odds ratio: 3.2, 95% CI = 0.8-12.2, and 4-octylphenol: 6 exposed
      cases and 5 exposed controls, adjusted odds ratio: 2.9, 95% CI = 10.8).

PMID- 9617383
TI  - Prevention of needle-stick injury by the scooping-resheathing method.
AB  - BACKGROUND: The objective of this study was to determine the effects of teaching
      the scooping-resheathing method on the incidence of needle-stick injuries in
      medical students. METHODS: Before starting their first clerkship, 81 medical
      students were given a 15-min lecture on the high incidence and dangers of needle
      stick injuries and a demonstration of the scooping-resheathing method. The number
      of needle-stick injuries that occurred during the 3-month clerkship was compared
      with the number reported by 86 medical students who had completed their first
      clerkship 1 year previously and had not been given such instruction. RESULTS:
      Compared with controls, the study group had a 3.8-fold lower risk of needle-stick
      injury (95% confidence interval, 2.0-7.4, P < 0.0001) and a 8.3-fold lower risk
      of multiple needle-stick injuries (95% confidence interval, 2.0-35.0, P < 0.001).
      Those in the study group, who consistently used the scooping method had a much
      lower risk of injury than those who did not (1 of 36 [2.8%] vs. 8 of 45 [17.4%],
      P = 0.039). CONCLUSIONS: We conclude that a lecture recommending the scooping
      resheathing method is effective in reducing the risk of needle-stick injuries in
      medical students during their first rotation. Because this is the first time that
      an intervention not requiring change in equipment has been successful, further
      studies are warranted to substantiate our findings and for extrapolation to other
      medical personnel in other cultural settings.

PMID- 9617384
TI  - Job strain, psychological distress, and burnout in nurses.
AB  - The first phase of this longitudinal study consisted of a questionnaire completed
      by a cohort of 1,891 nurses (aged 23-65 years) from six acute care hospitals from
      the province of Quebec. This study was set up to investigate the association
      between the psychosocial environment of work and mental health. After adjusting
      for confounding factors, a combination of high psychological demands and low
      decision latitude was associated with psychological distress and emotional
      exhaustion, one of the three dimensions of burnout. Social support at work,
      although associated with each of the mental health indicators, did not modify
      their association with job strain. The present study identified conditions of the
      work environment that are modifiable and provide the basis for interventions that
      focus beyond the modification of individual coping strategies.

PMID- 9617385
TI  - Comparison of self-reported and expert-observed physical activities at work in a
      general population.
AB  - Concerns about exposure assessment quality have impeded research to identify risk
      factors for ergonomic disorders. We compared self-reported and expert-observed
      estimates of work-related physical factors for participants in a study of carpal
      tunnel syndrome (CTS). We analyzed data from 61 subjects, including 28 CTS cases
      and 33 controls randomly samples from a case-control study with 417 participants.
      For 11 posture and manual materials handling factors, the median difference in
      mean exposure between self-reported and expert-observed exposure at work was less
      than 1/2 hour a day. Measurements by the two methods in this study agreed more
      often than expected by chance (median kappa 0.31 in cases and 0.28 in controls).
      Kappa differed significantly by case-control status for two factors: bending at
      the waist (kappa 0.79 in cases versus 0.28 in controls, P = 0.01) and twisting of
      the forearm (kappa 0.45 in cases versus -0.02 in controls, P = 0.02). Although
      imperfect, exposure information collected from workers' self-reports is useful
      for many ergonomic epidemiology studies.

PMID- 9617386
TI  - Mortality studies of metalworking fluid exposure in the automobile industry: VI.
      A case-control study of esophageal cancer.
AB  - BACKGROUND: Results are reported from a nested case-control study of 60
      esophageal cancer deaths among 46,384 automobile manufacturing workers
      potentially exposed to metalworking fluids (MWF) in machining and grinding
      operations. METHODS: By using incidence-density sampling, controls were selected
      with a sampling ratio of 20:1 from among co-workers who remained at risk by the
      age of death of the case, matched on race, gender, plant, and year of birth.
      Conditional logistic regression was used to evaluate the risk associated with
      cumulative exposure (mg/m3-years) to each of three types of metalworking fluid
      (straight, soluble, and synthetic MWF), as well as with years of exposure to
      selected components of MWF, including nitrosamines, sulfur, biocides, and several
      metals. RESULTS: Esophageal cancer was found to be significantly associated with
      exposure to both soluble and synthetic MWF in grinding operations. The odds
      ratios (ORs) for grinding with soluble MWF were elevated at 2.5 or greater in all
      categories of cumulative exposure, although the exposure-response trend was
      statistically significant only when exposure was measured as duration. Those with
      12 or more years exposure to soluble MWF in grinding operations experienced a 9.3
      fold relative risk of esophageal cancer mortality (95% CI = 2.1-42.1). The OR for
      ever grinding with synthetic MWF was 4.1 (95% CI = 1.1-15.0). Elevated risk was
      also associated with two agents found in both synthetic and soluble fluids,
      nitrosamines, and biocides. For exposure to nitrosamines, the OR was 5.4 (95% CI
      = 1.5-19.9); for biocides the OR was 3.8 (95% CI = 0.8-18.9). However, because
      the same workers were exposed to grinding with synthetics, nitrosamines and
      biocides, it was not possible to separate the specific risks associated with
      these components.

PMID- 9617387
TI  - Effects of the analytical treatment of exposure data on associations of cancer
      and occupational magnetic field exposure.
AB  - Epidemiological studies of cancer among workers exposed to magnetic fields have
      yielded inconsistent results. This variability may be partly explained by
      differences in study methods. To assess sensitivity to such methods, data from a
      previous study of brain cancer and leukemia among electric power company workers
      were reanalyzed using alternative models, which incorporated uncertainty about
      the intensity of historical exposures, alternative cut points for categorizing
      the exposure variable for analysis, and a range of lags for describing cancer
      latency. Mortality rate ratios for leukemia ranged from 0.8-1.5. For brain
      cancer, increasing cumulative magnetic field exposure was associated with
      increasing mortality in virtually all models, with rate ratios between 1.3-3.4
      for the most exposed workers. These rate ratios are consistent with previous
      analyses suggesting a 1.5-3.0-fold increase in the risk of brain cancer but no
      association with leukemia, and confirm that the previous results are not
      dependent on arbitrary decisions in applying the exposure data.

PMID- 9617388
TI  - The impact of initial job assignment on formaldehyde exposure among African
      American and white formaldehyde industry workers.
AB  - We compared initial job assignments of African-American and white employees at
      eight worksites that used formaldehyde between 1940 and 1979. Unexposed workers
      were excluded. Median, ambient air formaldehyde, 8-hour, time-weighted average
      (TWA8) exposure estimates were determined for each worksite. Job assignments with
      TWAs above the worksite's median TWA8 were called high formaldehyde exposed
      (HFE). Job assignments with TWAs less than or equal to the worksite's median TWA8
      for the same period were called lower formaldehyde exposed (LFE). Two worksites
      assigned black workers to HFE jobs in significantly higher proportions than white
      workers in some decades. One worksite assigned white workers in significantly
      higher proportions than black workers to HFE jobs in some decades. One worksite
      assigned racial groups in nearly equal proportions from 1940 to 1969. The
      remaining sites showed insignificant assignment disproportions (alpha = 0.05; Chi
      square < or = 3.841, 1 degree of freedom) for any period. No major trend was
      apparent across all plants and decades.

PMID- 9617389
TI  - Multiple exposure to arsenic, antimony, and other elements in art glass
      manufacturing.
AB  - Art glass manufacturing is one of the most interesting examples of exposure to
      complex mixtures. Among the raw materials used are silica sand, borax,
      carbonates, nitrates of Ca, Na, K, and a great number of compounds that are
      mainly oxides of As, Sb, Al, Zn, Cr, Ni, Sn, Se, Cd, Mn, Cu, Co, Fe, Nd, Er, Eu,
      and La. In six art glass factories that use As or Sb as fining agents, the
      exposure to these elements was investigated in 32 workers by means of
      environmental and biological monitoring. Analysis was conducted by atomic
      absorption spectrometry (AAS) and inductively coupled plasma mass spectrometry
      (ICP-MS). The results confirmed that As, which is the main carcinogen in glass
      production, reaches high air concentrations and is generally above the American
      Conference of Governmental Industrial Hygienists (ACGIH) threshold limit value
      time-weighted average (TLV-TWA) of 10 micrograms/m3. When partly substituted by
      antimonial compounds, As air concentrations dropped dramatically, while the air
      levels of Sb (which is considered less toxic but is classified as a class 2B
      carcinogen by IARC) were relatively low and below the ACGIH TLV-TWA of 500
      micrograms/m3. Exposure to As and Sb also differed in the three types of jobs
      investigated: As was high in oven chargers, Sb was higher in batch mixers, and
      both elements were low in makers-formers. Eleven to 18 elements were detected:
      arsenic, Al, Ba, Sb, Pb, and Zn were the elements most frequently measured (in
      tens, and in some cases hundreds, of micrograms/m3), followed by B, Li, Mn, Se,
      Sn, Sr, Ce, La, and Nd (in micrograms or in some cases tens of micrograms/m3. The
      results of biological monitoring for As, Sb, and other elements were in agreement
      with environmental monitoring data. We concluded that multiple detection of
      elements is a useful tool (or the evaluation of exposure to complex mixtures such
      as those used in the art glass industry and that such detection also allows a
      more accurate evaluation of related epidemiological data.

PMID- 9617390
TI  - The attitudes of occupational health personnel to smoking at work.
AB  - Attitudes of occupational health care professionals toward smoking and their
      activity to address smoking issues were investigated by a questionnaire survey.
      Data were also collected on employees' exposure to environmental tobacco smoke
      and on smoking policies that existed in workplaces. Questionnaires were mailed to
      all occupational health care centers (n = 1,004) in Finland. The prevalence of
      daily smokers was 9.6% among physicians and 3.6% among nurses; 15% and 11%,
      respectively smoked occasionally. Smoking restrictions were enforced in more than
      70% of all workplaces, but only 3.6% of them had a total smoking ban. Nonsmoking
      professionals were in favor of smoke-fee workplaces and smoking restrictions
      significantly more often than their smoking colleagues. Nonsmokers also regarded
      smoking as a serious problem to the organizational climate of workplaces. Almost
      half of nonsmoking respondents, but only 11% of daily smokers, would totally ban
      smoking in workplaces. Although the personal smoking status of the respondent had
      a strong effect on attitudes to smoking regulations, it did not have a clear
      influence on interest in discussing smoking issues when seeing patients. Nurses
      were more active in addressing smoking issues than physicians. Occupational
      health professionals of large companies reported stricter smoking policies at
      work than those who represented small enterprises

PMID- 9617391
TI  - Objective assessment of ocular and respiratory alterations in employees in a sick
      building.
AB  - BACKGROUND: Sick building syndrome (SBS) is a constellation of diffuse,
      "irritative" symptoms predominantly involving the eyes and the respiratory tract.
      To date, the effects of working in a "sick building" have not been adequately
      assessed using objective measures. We undertook the present study to determine
      whether objective alterations could be found in the eyes and respiratory' tracts
      of employees working in an office building in which a high rate of SBS had been
      reported in the preceding year. METHODS: We studied 163 office workers: 87
      workers from a modern, air-conditioned building (the sick building), and 76
      employees employed in three traditional-style office buildings (the comparison
      buildings). After being surveyed for SBS symptoms, all subjects underwent a
      series of objective tests, including spirometry, a methacholine test, prick tests
      for aeroallergens, and submitted tear samples. In addition, Schirmer's test and
      the break-up time test were used to explore for potential ocular effects of sick
      building exposure. RESULTS: Employees in the sick building complained more
      frequently of ocular symptoms, upper-airway disturbances, and general and
      respiratory' symptoms than did employees in the comparison buildings; prick tests
      were positive in 20% and 17.4%, respectively. Groups did not differ significantly
      on spirometry measures. Bronchial hyperreactivity to methacholine (PD15 = 16.348
      mumol) was present in 20.5% of the sick building workers and in 16.2% of
      comparison buildings workers. Methacholine dose-response slope values were
      similar. Stability of tear film was significantly reduced (P < 0.01) in the
      employees in the sick building compared with employees in the comparison
      buildings. CONCLUSIONS: Our results indicate that (1) atopy does not seem to
      influence the prevalence of SBS symptoms, and (2) the lower respiratory tract
      seems unaffected by exposure to a "sick building," but (3) alterations in tear
      film stability do exist after such exposure.

PMID- 9617392
TI  - Re: "Dermal absorption potential of industrial chemicals: criteria for skin
      notation".

PMID- 9617394
TI  - Ethics.

PMID- 9617395
TI  - Development and validation of the quality of life outcome measure (questionnaire)
      for chronic anterior cruciate ligament deficiency.
AB  - A patient-based, subjective outcome measure for chronic anterior cruciate
      ligament deficiency was developed, pretested, and validated. The development of
      the outcome measure was completed in four stages: 1) item generation (167 items),
      2) item reduction (by surveying 79 patients), 3) questionnaire formation and
      pretesting (20 patients), and 4) reliability, responsiveness, and validity
      assessment (100 patients). This disease-specific quality of life measure is a 32
      item questionnaire using a 100-mm visual analog scale response format. Face
      validity was derived from extensive direct patient input. Content validity was
      determined by consensus among 20 knee surgeons. There was no significant
      difference on test-retest reliability, with an overall average error of 6%. The
      outcome measure demonstrated responsiveness to clinical change correctly in 21 of
      25 patients (84%). Construct validity was shown by the ability of the
      questionnaire to measure the full spectrum of disease; scores ranged from 8 to 99
      out of a maximum score of 100. The questionnaire was able to distinguish patients
      who went on to have surgery (average score, 31) from those who would be treated
      nonoperatively (average score, 79). The quality of life outcome measure for
      chronic anterior cruciate ligament deficiency is the first subjective knee scale
      of its kind to be validated to measure quality of life in patients with chronic
      anterior cruciate ligament deficiency.

PMID- 9617396
TI  - Heavy-load eccentric calf muscle training for the treatment of chronic Achilles
      tendinosis.
AB  - We prospectively studied the effect of heavy-load eccentric calf muscle training
      in 15 recreational athletes (12 men and 3 women; mean age, 44.3 +/- 7.0 years)
      who had the diagnosis of chronic Achilles tendinosis (degenerative changes) with
      a long duration of symptoms despite conventional nonsurgical treatment. Calf
      muscle strength and the amount of pain during activity (recorded on a visual
      analog scale) were measured before onset of training and after 12 weeks of
      eccentric training. At week 0, all patients had Achilles tendon pain not allowing
      running activity, and there was significantly lower eccentric and concentric calf
      muscle strength on the injured compared with the noninjured side. After the 12
      week training period, all 15 patients were back at their preinjury levels with
      full running activity. There was a significant decrease in pain during activity,
      and the calf muscle strength on the injured side had increased significantly and
      did not differ significantly from that of the noninjured side. A comparison group
      of 15 recreational athletes with the same diagnosis and a long duration of
      symptoms had been treated conventionally, i.e., rest, nonsteroidal
      antiinflammatory drugs, changes of shoes or orthoses, physical therapy, and in
      all cases also with ordinary training programs. In no case was the conventional
      treatment successful, and all patients were ultimately treated surgically. Our
      treatment model with heavy-load eccentric calf muscle training has a very good
      short-term effect on athletes in their early forties.

PMID- 9617397
TI  - Hyperbaric oxygen in the treatment of acute muscle stretch injuries. Results in
      an animal model.
AB  - Hyperbaric oxygen therapy is an established therapy in several areas of clinical
      medicine. However, studies have produced conflicting results regarding its
      efficacy for sports-related soft tissue injuries. This study examines the use of
      hyperbaric oxygen therapy after an acute muscle stretch injury in an animal
      model. Two groups of rabbits (nine in each group) were subjected to a partial
      stretch injury to the tibialis anterior muscle-tendon unit. For all 18 animals,
      the injuries were induced in the left limb, and the uninjured right limb served
      as a sham-operated control. In group 1, the animals were exposed to hyperbaric
      oxygen (> 95% O2 at 2.5 atm) for 60 minutes daily for 5 days. Treatment began 24
      hours after injury. Group 2 animals were not exposed to hyperbaric oxygen.
      Evaluation 7 days after injury demonstrated a functional deficit (percent ankle
      isometric torque; injured side versus uninjured side) of 14.9% +/- 5.5% (mean +/-
      SD) for the treated group and 47.5% +/- 5.4% for the untreated group,
      representing a statistical difference using the Behrens-Fisher version of the t
      test (P = 0.001). Morphologic studies revealed more complete healing in the
      treated group. This study suggests that hyperbaric oxygen therapy may play a role
      in accelerating recovery after acute muscle stretch injury. Further studies are
      needed before definitive conclusions and treatment recommendations can be made.

PMID- 9617398
TI  - Arthroscopic transglenoid stabilization versus open anchor suturing in traumatic
      anterior instability of the shoulder.
AB  - Sixty-two consecutive patients with recurrent traumatic anterior instability of
      the shoulder were prospectively observed. Thirty patients were observed after
      arthroscopic stabilization, and 32 were observed after open Bankart repair during
      a mean follow-up of 36 and 40 months, respectively (range, 24 to 60 months for
      both groups). To reattach the labrum, the arthroscopic technique used
      transglenoid sutures and the open technique used bone anchors. Redislocation
      occurred in two patients (6%) in the open repair group and in five patients (17%)
      in the arthroscopic repair group. Three of the five patients with redislocations
      in the arthroscopic repair group underwent reoperation. According to the criteria
      of Rowe et al., 29 patients (90.6%) who had open repair and 24 patients (80%) who
      had arthroscopic repair had good-to-excellent results. The patients averaged 90.6
      points in the open repair group and 83.1 points in the arthroscopic repair group
      postoperatively. Little or no limitations in their postoperative sport activities
      were reported by 30 patients (94%) who underwent open repair and by 25 patients
      (83%) who had arthroscopic repair. Despite similar patient populations and using
      arthroscopic examination to select the type of repair in both groups, the results
      of arthroscopic shoulder stabilization are inferior to those of the classic open
      Bankart procedure.

PMID- 9617399
TI  - The deltoid muscle origin. Histologic characteristics and effects of subacromial
      decompression.
AB  - The histologic characteristics of the deltoid muscle attachment to nine cadaveric
      acromia were studied using light microscopy. The deltoid muscle attaches to the
      anterior and lateral acromion primarily by direct tendinous attachment. The
      muscle attaches to the dorsal side of the acromion by periosteal fiber
      attachment. In the specimens studied, a hypothetical acromioplasty of 4 mm would
      release, on average, 41% of the direct fiber attachment, and a 6-mm acromioplasty
      would release 69% for all zones examined histologically. The functional and
      clinical effects of these findings are not known, but the deltoid muscle would be
      released by arthroscopic acromioplasty in areas where bone is removed.

PMID- 9617400
TI  - Significance of the single-legged hop test to the anterior cruciate ligament
      reconstructed knee in relation to muscle strength and anterior laxity.
AB  - We investigated the significance of the single-legged hop test to the anterior
      cruciate ligament-reconstructed knee as it specifically relates to knee muscle
      strength recovery and residual anterior laxity. The hop test was conducted on 107
      patients with unilateral anterior cruciate ligament-reconstructed knees (78
      semitendinosus tendon autografts and 29 bone-patellar tendon-bone autografts).
      Patients were tested an average of 2 years after surgery. Correlation coefficient
      analyses determined whether the relationship between knee muscle strength
      recovery and the hop test was invariant across all levels of residual anterior
      laxity and whether the relationship between residual anterior laxity and the hop
      test was invariant across levels of quadriceps muscle strength recovery.
      Furthermore, we examined the effect of graft harvest site on the hop index.
      Positive correlations were found between the hop index and muscle strength index
      at all levels of residual anterior laxity (P < 0.05), but these correlation
      coefficients were relatively low. There were no apparent correlations between the
      hop index and residual anterior laxity at all levels of quadriceps muscle
      strength recovery. There was no significant difference in the average hop index
      between the semitendinosus tendon autograft group and the bone-patellar tendon
      bone autograft group.

PMID- 9617401
TI  - Isolated sectioning of the medial and posteromedial capsular ligaments in the
      posterior cruciate ligament-deficient knee. Influence on posterior tibial
      translation.
AB  - This study was undertaken to determine the contribution of various structures in
      the posterior cruciate ligament-deficient knee in resisting posterior tibial
      translation. With "isolated" injuries to the posterior cruciate ligament, the
      amount of posterior translation will decrease with the posterior drawer test as
      the knee is taken from neutral to internal tibial rotation. The present study was
      performed to conclusively determine the anatomic structure responsible for this
      clinical observation. The TestStar device was used to perform single-plane
      posterior drawer tests in 14 cadaveric knee specimens. The tests were performed
      with the knee in neutral tibial rotation and in 20 degrees of internal tibial
      rotation. The intact knee was tested and then the knee was tested after
      sequential sectioning of the meniscofemoral ligaments, the posterior cruciate
      ligament, the posteromedial capsule, and the superficial medial collateral
      ligament. With the knee in neutral rotation, posterior translation continued to
      increase as each structure was sectioned. With the knee in internal tibial
      rotation, posterior displacement was significantly less than in neutral rotation
      for each state until the superficial medial collateral ligament was sectioned;
      posterior translation was increased after its sectioning. Our data demonstrate
      that the superficial medial collateral ligament is the structure responsible for
      a decrease in posterior tibial translation in the posterior cruciate ligament
      deficient knee.

PMID- 9617402
TI  - Determination of the in situ forces in the human posterior cruciate ligament
      using robotic technology. A cadaveric study.
AB  - We examined the in situ forces in the posterior cruciate ligament as well as the
      force distribution between its anterolateral and posteromedial bundles. Using a
      robotic manipulator in conjunction with a universal force-moment sensor system,
      we applied posterior tibial loads from 22 to 110 N to the joint at 0 degrees to
      90 degrees of knee flexion. The magnitude of the in situ force in the posterior
      cruciate ligament and its bundles was significantly affected by knee flexion
      angle and posterior tibial loading. In situ forces in the posterior cruciate
      ligament ranged from 6.1 +/- 6.0 N under a 22-N posterior tibial load at 0 degree
      of knee flexion to 112.3 +/- 28.5 N under a 110-N load at 90 degrees. The force
      in the posteromedial bundle reached a maximum of 67.9 +/- 31.5 N at 90 degrees of
      knee flexion, and the force in the anterolateral bundle reached a maximum of 47.8
      +/- 23.0 N at 60 degrees of knee flexion under a 110-N load. No significant
      differences existed between the in situ forces in the two bundles at any knee
      flexion angle. This study provides insight into the knee flexion angle at which
      each bundle of the posterior cruciate ligament experiences the highest in situ
      forces under posterior tibial loading. This information can help guide us in more
      accurate graft placement, fixation, and tensioning, and serve as an assessment of
      graft performance.

PMID- 9617403
TI  - The relationship between intercondylar notch width of the femur and the incidence
      of anterior cruciate ligament tears. A prospective study.
AB  - For 714 consecutive patients who underwent autogenous patellar tendon graft
      anterior cruciate ligament reconstructions we intraoperatively measured
      intercondylar notch width. We prospectively recorded height, weight, sex, and
      which patients subsequently tore their contralateral anterior cruciate ligament
      or the 10-mm autograft. The patients were divided into two groups based on notch
      width (group 1, < or = 15 mm; group 2, > or = 16mm. The mean notch width was 13.9
      +/- 2.2 mm for women and 15.9 +/- 2.5 mm for men. There was no statistically
      significant difference in notch width between height groups for women or men.
      Analysis showed that, with height and weight as covariates, women had
      statistically significantly narrower notches than men. Twenty-three of 388
      patients in group 1 and 4 of 326 patients in group 2 tore their contralateral
      anterior cruciate ligaments. Within groups, no statistically significant
      differences in contralateral tear rates existed between men and women. Once the
      men and women had reconstructions with equally sized 10-mm autografts, there was
      no difference in graft tear rate between groups or between men and women. Our
      results show that patients with narrower notches have a higher incidence of
      tearing their contralateral anterior cruciate ligament. After reconstruction with
      a 10-mm autograft, the incidence of graft rupture is the same for men and women.

PMID- 9617404
TI  - Articular cartilage changes seen with magnetic resonance imaging-detected bone
      bruises associated with acute anterior cruciate ligament rupture.
AB  - Occult osteochondral lesions (bone bruises) have been documented on magnetic
      resonance images in more than 80% of patients sustaining acute anterior cruciate
      ligament ruptures. Despite the high prevalence of these lesions, little is known
      about the histologic changes in the adjacent articular cartilage. Ten patients
      with acute anterior cruciate ligament ruptures who had a preoperatively
      documented (by magnetic resonance imaging) geographic bone bruise at the sulcus
      terminalis on the lateral femoral condyle underwent a 3-mm diameter trephine
      biopsy of the articular cartilage and subchondral bone overlying the bone bruise
      at the time of anterior cruciate ligament reconstruction. Biopsy samples of the
      articular cartilage and subchondral bone were stained with hematoxylin and eosin
      and toluidine blue. All patients had significant arthroscopic and histologic
      articular cartilage irregularity in the area overlying the bone bruise.
      Arthroscopic findings of the articular cartilage included softening (dimpling),
      fissuring, or overt chondral fracture. Histologic examination revealed
      degeneration of the chondrocytes and loss of toluidine blue staining in the
      articular cartilage (loss of proteoglycan). There was necrosis of osteocytes in
      the subchondral bone, and empty lacuna were visible. This study defines the exact
      histologic changes of the articular cartilage overlying a geographic bone bruise
      secondary to an acute anterior cruciate ligament tear. Our findings suggest that
      a geographic bone bruise found on magnetic resonance imaging indicates
      substantial damage to normal articular cartilage homeostasis.

PMID- 9617405
TI  - Evaluation of the intraosseous and extraosseous blood supply to the distal
      femoral condyles.
AB  - Osteonecrosis of the distal femur occurs more often in the medial femoral condyle
      than in the lateral femoral condyle, but the vascular supply to these regions has
      not previously been described. Twelve fresh adult cadaver legs were injected with
      india ink or latex via the femoral artery and then meticulously dissected to
      evaluate the extraosseous blood supply. After all soft tissue was removed, the
      intraosseous blood supply was evaluated using a modified Spateholtz technique.
      The vascular structures at risk during posterior cruciate ligament reconstruction
      were also identified. The analysis of the extraosseous arterial supply
      demonstrated that the superior and inferior lateral genicular arteries combine to
      supply the lateral femoral condyle. The medial femoral condyle is supplied
      primarily by the superior medial genicular artery and other lesser branches of
      the popliteal artery. The intraosseous supply to the lateral condyle was shown to
      consist of an arcade of vessels providing multiple branches to the subchondral
      bone with no obvious "watershed" region of limited vascularity. The intraosseous
      supply to the medial condyle appeared to consist of a single nutrient vessel
      supplying the subchondral bone with an apparent watershed area of limited supply.
      A potentially significant difference exists between the intraosseous and
      extraosseous blood supply to the medial and lateral femoral condyles that may
      explain the higher frequency of ischemic events occurring in the medial femoral
      condyle. The close proximity of the extraosseous vessels to the medial femoral
      condyle and the standard femoral tunnel used during posterior cruciate ligament
      reconstruction may explain the occurrence of avascular necrosis after this
      procedure.

PMID- 9617406
TI  - Medial elbow joint laxity in professional baseball pitchers. A bilateral
      comparison using stress radiography.
AB  - Injuries to the ulnar collateral ligament frequently occur in throwing athletes
      because of large, repetitive valgus stresses to the elbow during the cocking and
      acceleration phases of throwing. Identification of injury to this ligament is
      important in evaluating the throwing elbow. The purpose of this study was to
      determine whether differences in medial elbow laxity exist between the dominant
      and nondominant extremities in uninjured baseball pitchers. Forty uninjured
      professional baseball pitchers were tested bilaterally with a Telos GA-IIE stress
      radiography device. Joint space width between the trochlea of the humerus and the
      coronoid process of the ulna was measured on anteroposterior radiographs obtained
      with no stress applied and with a 15-daN valgus stress. Results showed
      significant differences between the medial joint space opening of the dominant
      and nondominant elbows with no stress applied. With stress, the dominant elbow
      opened 1.20 +/- 0.97 mm, while the nondominant elbow opened 0.88 +/- 0.55 mm. A
      significantly greater difference in medial joint space opening between the
      stressed and unstressed elbows was measured in the dominant elbow compared with
      the nondominant elbow (0.32 +/- 0.42 mm). This study identifies increased medial
      elbow laxity in the dominant arm in uninjured pitchers.

PMID- 9617407
TI  - Elbow valgus stress radiography in an uninjured population.
AB  - Valgus instability of the elbow joint is a clinical diagnosis. However, many
      authors describe valgus stress radiographs as an aid in making this diagnosis. We
      studied valgus stress radiographs of 20 men (40 elbows) and 20 women (40 elbows),
      none with a history of elbow trauma or instability. The medial ulnohumeral
      distance was measured with no stress, valgus stress by gravity, and an applied
      valgus stress of 25 N (approximately 5 pounds). Measurements were made with the
      elbow positioned in extension and in 30 degrees of flexion. The increase in
      medial ulnohumeral gapping with either gravity or 5 pounds of stress was
      statistically significant at both extension and 30 degrees of flexion compared
      with the unstressed condition. The difference in ulnohumeral gapping between
      gravity stress and 5 pounds of valgus stress in extension and in 30 degrees of
      flexion was also significant. We found no differences with regard to hand
      dominance or sex. We conclude that uninjured elbows have significant medial
      ulnohumeral gapping on valgus stress radiography. Although this is an important
      tool in diagnosing valgus instability of the elbow, it may yield a false-positive
      assessment of valgus instability. Valgus stress radiographs comparing
      contralateral elbows may reduce the false-positive rate since there appears to be
      no significant difference in medial ulnohumeral gapping between the two elbows.

PMID- 9617408
TI  - Distal biceps brachii tendon repair. An in vitro biomechanical study of tendon
      reattachment.
AB  - Clinical reports suggest that suture anchors can simplify repair of distal biceps
      tendon avulsions. In this study, fixation strengths of Mitek and Statak suture
      anchors were compared with strength of reattachment using transosseous suture
      tunnels in eight cadaveric radii. Cyclic loading and load-to-failure testing were
      performed: No specimen failed during testing to 50 N for 3600 cycles: however,
      four of the Mitek anchors and one of the Statak anchors protruded out of the
      medullary canal. The mean load to failure of the Mitek suture anchor complexes
      was 220 +/- 54 N, that of the Statak suture anchor complexes was 187 +/- 64 N,
      and that of the transosseous sutures was 307 +/- 142 N. There was no significant
      difference in the failure load or mechanism of failure between the Statak and
      Mitek anchors. Transosseous sutures failed at significantly greater loads on
      static testing than the suture anchors. Cyclic loading results suggest that the
      bony fixation achieved using these three techniques should be sufficient to allow
      immediate passive mobilization of the elbow after surgery. Protrusion of the
      suture anchors out of the tuberosity during cyclic loading is a concern because
      of potential development of a gap at the repair site and interference with
      forearm rotation.

PMID- 9617409
TI  - Concussion history in elite male and female soccer players.
AB  - A unique feature of soccer is the purposeful use of the head for controlling,
      passing, and shooting a soccer ball. Some concern has been expressed in the
      literature on the cumulative effects of heading on soccer players. Certain
      neurophysiologic and neuropsychologic changes have been reported in current or
      retired players, with heading being blamed. A major factor that could influence
      some of the findings is a player's history of concussive episodes, which are
      known to influence brain function. These episodes can occur during aspects of the
      game other than heading. We interviewed all male and female soccer players (N =
      137, average age = 20.5 years) who competed at the U.S. Olympic Sports Festival
      in 1993. The mechanisms of injuries, frequency, and sequelae were determined.
      There were 74 concussions in 39 male players (grade I = 50) and 28 concussions in
      23 female players (grade I = 19). For the men, 48 of the 74 episodes were from
      collisions with another player. For the women, 20 of 28 were from such
      collisions. Headaches, being "dazed," and dizziness were the most common symptoms
      reported. Based on concussion history, the odds are 50% that a man, and 22% that
      a woman, will sustain a concussion within a 10-year period. The data indicate
      that concussions from player-to-player contact are a frequent hazard in soccer.
      Head injuries incurred this way may be more of an influence for published
      findings of physiologic and psychologic deficiencies than routine heading of the
      soccer ball.

PMID- 9617410
TI  - Exercise-induced compartment syndrome in the flexor-pronator muscle group. A case
      report and pressure measurements in volunteers.
AB  - Compartment syndrome is caused by an increase in intracompartmental pressure
      above the capillary level, preventing capillary flow. The acute onset of symptoms
      occurs after events such as fracture, soft tissue trauma, and revascularization
      and usually necessitates prompt fasciotomy to avoid loss of function or even
      necrosis of the enclosed muscle. Compartment syndromes in athletes are of a
      recurrent nature and are usually referred to as chronic. Nonoperative treatment
      is often successful. Although compartment syndromes can occur in several anatomic
      regions, the most commonly seen in athletes involve the leg. Chronic compartment
      syndromes of the upper extremity are rare, and only a few cases have been
      reported in the literature. The intracompartmental pressures causing chronic
      symptoms in these cases ranged between 22 mm Hg at rest and 40 mm Hg after 30
      minutes of exercise. Under maximal contraction, a pressure of 58 mm Hg has been
      recorded. The object of this paper is to report a case of a tennis player where
      much higher flexor-pronator muscle intracompartmental pressures than those noted
      above were recorded. We compared the intracompartmental pressure data of this
      patient with intracompartmental pressures measured in six symptom-free
      volunteers.

PMID- 9617411
TI  - Graft fixation strength with arthroscopic anterior cruciate ligament
      reconstruction. Two-incision rear entry technique compared with one-incision
      technique.
AB  - To compare the fixation strengths of two arthroscopic anterior cruciate ligament
      reconstruction techniques, we harvested 10-mm bone-patellar tendon-bone grafts
      with 25-mm bone plugs from 12 fresh-frozen cadaveric knees. One knee of each pair
      was fixed using Acufex instruments and the two-incision technique; one knee was
      fixed using Arthrotek instruments and the one-incision technique. We used
      cannulated 9 x 25 mm Kurosaka screws for femoral and tibial tunnel fixation. All
      knees were mounted on the Instron Test System and were stressed to failure by
      recreating a pivot shift maneuver. The one-incision technique graft fixation was
      significantly stronger (mean failure, 695 N) than that with the two-incision
      technique (mean failure, 593 N). In all one-incision technique knees, either the
      patellar tendon graft avulsed off a bone plug or the plug broke. In five of six
      two-incision technique knees, the tibia bone plug pulled out around the
      interference screw. Patellar tendon graft length ranges from 90 to 105 mm, and
      the average two-incision technique tunnel length is 120 mm. The interference
      screw compressed the femoral bone plug into conical bone but compressed the
      tibial bone plug into cancellous bone in the two-incision technique, while in the
      one-incision technique the bone plug was compressed into cortical bone on both
      sides.

PMID- 9617412
TI  - Different regional healing rates with the outside-in technique for meniscal
      repair.
AB  - Fifty-one patients with meniscal repair using the outside-in technique were
      reassessed with second-look arthroscopic procedures (N = 15), arthrographic
      examination (N = 41), magnetic resonance imaging (N = 36), or a combination of
      these techniques. Forty-one medial and 10 lateral menisci were repaired. The
      average clinical follow-up was 15 months (range, 3 to 80). Forty-five of 51
      patients had tears that were located in or extended into the posterior horn of
      the medial or lateral meniscus. Complete healing occurred in 23 menisci (45%),
      partial healing was observed in 16 (15 medial, 1 lateral) (32%), and no healing
      occurred in 12 (24%). Remarkably, in all 15 patients who had tears extending from
      the posterior to the middle third of the medial meniscus that were partially
      healed, it was always the posterior third that had not fully healed. This finding
      is statistically significant. In addition, the middle third of these menisci had
      not fully healed in five patients. No healing occurred in the two patients with
      tears in the posterior third of the medial meniscus. Poor healing with the
      outside-in technique was observed in patients with tears into the posterior horn
      of the medial meniscus. For tears in the middle and anterior portion of the
      medial meniscus, as well as all lateral meniscus tears, the outside-in technique
      is our current method of choice.

PMID- 9617413
TI  - Results of derotational humeral osteotomy in posterosuperior glenoid impingement.
AB  - We identified 20 throwing athletes who continued to have pain after articular
      debridement for posterosuperior impingement syndrome. These patients were unable
      to resume sports, and we subsequently performed a derotational humeral osteotomy
      with a myorraphy of the subscapularis muscle. Patients were observed for an
      average of 46 months (range, 12 to 69). Eleven patients were able to resume the
      same sport at the same level, five resumed the same sport at a lower level, three
      changed sport secondary to persistent pain, and the last patient did not resume
      any sport and was worse after surgery. Patients returned to sports at an average
      of 6 months postoperatively (range, 4 to 44) and to their previous level of
      sports at an average of 12 months (range, 8 to 18). The mean increase in humeral
      retroversion was 29 degrees (range, 18 degrees to 44 degrees) Three women with
      preoperative multidirectional hyperlaxity were considered to have failed results.
      Derotational humeral osteotomy can be considered in the throwing athlete with
      posterosuperior impingement after failure of all other means of treatment.
      Careful patient selection and preoperative evaluation of humeral retroversion is
      important. Best results can be achieved in a motivated patient with low
      retroversion (< 10 degrees). If retroversion is normal (20 degrees to 30
      degrees), the surgical indication is unclear. We do not recommend this surgery
      for patients with hyperlaxity.

PMID- 9617414
TI  - Knee joint immobilization decreases aggrecan gene expression in the meniscus.
AB  - Aggrecan is the major proteoglycan of the meniscus, and its primary function is
      to give the meniscus its viscoelastic compressive properties. The objective of
      this study was to determine the effect of joint immobilization on aggrecan gene
      expression in the meniscus. The right hindlimbs of six mature beagles were knee
      cast-immobilized in 90 degrees of flexion and supported by a sling to prevent
      weightbearing, while the contralateral limb was left free to bear weight. The
      animals were sacrificed at 4 weeks, and the anterior and posterior halves of the
      medial and lateral menisci were analyzed separately. Analysis of aggrecan gene
      expression by quantitative polymerase chain reaction showed decreased aggrecan
      gene expression in menisci from immobilized knees (P < 0.01, two-way analysis of
      variance). Aggrecan gene expression decreased by a factor of 2 to 5.5 in the
      different regions examined. Analysis of the composition of the meniscus also
      showed decreased proteoglycan content and increased water content with
      immobilization (P < 0.05, two-way analysis of variance). These results show that
      joint immobilization can significantly affect meniscal cellular activity and
      composition and can therefore potentially affect meniscal function.

PMID- 9617415
TI  - Acute Achilles tendon rupture in badminton players.
AB  - All patients with badminton-related acute Achilles tendon ruptures registered
      during 1990 to 1994 at the University Hospital of Umea were retrospectively
      followed up using a questionnaire. Thirty-one patients (mean age, 36.0 years), 27
      men and 4 women, were included. Thirty patients (97%) described themselves as
      recreational players or beginners. The majority of the injuries (29 of 31, 94%)
      happened at the middle or end of the planned game. Previous local symptoms had
      been noticed by five patients (16%). Long-term results showed that patients
      treated with surgery had a significantly shorter sick leave absence than patients
      treated without surgery (50 versus 75 days). There was no obvious selection
      favoring any treatment modality. None of the surgically treated patients had
      reruptures, but two reruptures occurred in the nonsurgically treated group. There
      seemed to be fewer remaining symptoms and a higher sports activity level after
      the injury in the surgically treated group. Our results indicate that local
      muscle fatigue may interfere with strength and coordination. Preventive measures
      such as specific treatment of minor injuries and adequate training of strength,
      endurance, and coordination are important. Our findings also indicate that
      surgical treatment and careful postoperative rehabilitation is of great
      importance among badminton players of any age or sports level with Achilles
      tendon rupture.

PMID- 9617416
TI  - Evaluation and treatment of posterior cruciate ligament injuries.
AB  - Improved basic science data on the anatomy and biomechanics of the human
      posterior cruciate ligament have provided the orthopaedic surgeon with new
      information on which to base treatment decisions. Injuries to the posterior
      cruciate ligament are reported to comprise approximately 3% of all knee ligament
      injuries in the general population and as high as 37% in an emergency department
      setting. While the diagnosis of a posterior cruciate ligament injury can often be
      made with a physical examination, ancillary studies such as radiographs and
      magnetic resonance images can be very helpful in detecting associated ligament
      and bony injuries. In general, most partial (grades I and II) posterior cruciate
      ligament injuries can be treated nonoperatively. However, surgical reconstruction
      is usually recommended for those posterior cruciate ligament injuries that occur
      in combination with other structures. In this review, current surgical techniques
      of posterior cruciate ligament reconstruction based on anatomic and biomechanical
      studies will be discussed.

PMID- 9617417
TI  - A statistics primer. Validity and reliability.

PMID- 9617418
TI  - [Primary and secondary surfactant deficiency: implications for therapy. Satellite
      Symposium. 23rd Annual Session of the German-Austrian Society for Neonatology and
      Pediatric Intensive Medicine. Munster, 17 October 1997].

PMID- 9617419
TI  - [Malignant hyperthermia registry--a contribution to greater patient safety].

PMID- 9617420
TI  - [Economic aspects of anesthesia. II. Cost control in clinical anesthesia].
AB  - The primary scope of economic analyses is the quantification of the costs (input)
      in relation to the results (outcome, output). According to whether a similar or
      different dimension of outcome parameters is chosen, it is possible to
      differentiate between cost minimisation, cost effectiveness, cost benefit and
      cost utility analyses. Decision trees and sensitivity analyses serve to develop
      or examine cost outcome studies. The principal perspective of economic analysis
      is of crucial significance. In the present overview of cost control programmes in
      clinical anaesthesia, the perspective chosen throughout is that of budget
      responsibility in a department of anaesthesiology. With regard to economic
      factors in clinical anaesthesiology, the cost of medical and nursing staff
      represents the largest cost block. It is, therefore, essential that personnel is
      efficiently employed, i.e. how the perioperative procedure is organised. In the
      area of material costs, blood products--including coagulation factors and plasma
      substitutes--are particularly cost intensive, followed by medical products and
      drugs, especially muscle relaxants and inhalational anaesthetics. In the
      perioperative context, the costs of anaesthesia personnel account for 5-15% of
      the total costs of patient care, while material costs account for 2-10%. In view
      of this small portion of the total costs, cost control programmes in anaesthesia
      can only make a relatively small contribution to reducing overall cost. However,
      it must be realised that anaesthesia care is vitally important for the
      perioperative process which means that in this context cost-effectiveness
      interventions have consequences that also affect other fields, e.g. postoperative
      pain service besides anaesthesia. In conducting economic analyses, cost
      considerations or reductions cannot be targeted alone, but must always also
      integrate outcome aspects so that costs and quality are regarded in relation to
      one another.

PMID- 9617421
TI  - [A remote access system for inquiry of centrally stored data on patients
      suspected of malignant hyperthermia . A prototypical development for the
      Internet].
AB  - OBJECTIVES: Malignant hyperthermia (MH) is an inherited, potentially life
      threatening syndrome of the skeletal muscles. It is a life-threatening
      complication of anaesthesia with a high mortality (8-10%). The risk of the
      patient during anaesthesia due to an overlooked predisposition for MH can be
      reduced by organisational measures, such as, all data of MH-susceptible patients
      and their families known in Germany must be brought together in a central
      register, MH-relevant data of patients must be readily retrievable, optional oral
      advice for those making an inquiry must be available. METHODS: To achieve this
      goal, a client-server system has been implemented: Standard Multimedia personal
      computers installed at the user's (anaesthetist's) site, linked to the Internet,
      will act as clients. On a server, relevant data of patients concerning MH
      susceptibility are integrated in a central database. The newly developed software
      of this project ensures the legally prescribed data security on the server and
      the data routes. At the client's site, standard software together with
      automatically installed programmes from the server using Java applets ensure easy
      use and maintenance. IMPLEMENTATION: The total system was implemented and tested.
      Its functionality and high availability was demonstrated during this test period.
      Relevant aspects of data security were successfully examined by the data security
      officer of the University Hospitals of Baden-Wurttemberg. The user can optionally
      call a multifunctional teleconference which secures on-line advice if needed.
      This system demonstrates a safe and quick retrieval of MH relevant data of
      patients via Internet while at the same time guaranteeing all aspects of data
      protection and security. CONCLUSION: A prototypical database access system is
      described. It ensures safe access to patient data via Internet, while
      guaranteeing all aspects of data security.

PMID- 9617422
TI  - [Regional distribution of predisposition to maligant hyperthermia in Germany:
      tate in 1997].
AB  - Malignant hyperthermia (MH) is a rare autosomally dominantly hereditary and
      potentially life-threatening disease. The prevalence of the genetic MH
      predisposition is estimated as 1:10,000 to 1:20,000. In Germany no data on the
      regional distribution are available. Therefore, the purpose of this investigation
      is to summarise and present the epidemiological data of all German MH
      laboratories. Nine German hospitals offer the specific in vitro contracture test
      to diagnose the MH predisposition. All German MH laboratories carry out the
      examination in accordance with the standardised protocol of the European
      Malignant Hyperthermia Group. The laboratories were asked to provide the number
      of all patients investigated, excluding those suffering from other neuromuscular
      diseases, separated according to diagnostic groups and their places of residence,
      the number of the identified MH-families as well as the number of the clinically
      suspected and investigated MH cases with their places of residence. Eight MH
      laboratories provided the requested data. Until September 1997 a total of 2620
      patients were investigated. In 865 patients (34%) MH suspicion was confirmed
      (diagnosis: MHS). 1494 patients (56%) were released by investigation from MH
      suspicion (diagnosis: MHN). In 261 patients (10%) the MH-predisposition remained
      unsolved (diagnosis: MHE). 580 MH families were identified. Among 2620 patients
      757 were clinically suspected MH cases. 35% of these suspected MH cases were
      classified as MHS, 10% as MHE and 55% as MHN. The documentation of the patients
      places of residence classified as MHS and MHE into a map of Germany demonstrates
      an exhaustive distribution with an increased regional prevalence in the areas of
      the MH laboratories. This concentration in the area of the MH laboratories
      becomes even more evident, when the places of residence of the MH suspected cases
      are demonstrated. In conclusion, the distribution of the MH predisposition is
      uniform and exhaustive in Germany. The presented regional concentration of
      clinically suspected MH cases among the MH laboratories is mainly interpreted as
      an expression of effective regional education and information. Considering the
      overall incidence of the MH predisposition as described above only 15-20% of the
      MH patients have so far been identified. The MH laboratories have already
      released about 10,000 patients from the suspicion of MH predisposition. A
      preliminary prevalence of at least 1:60,000 to 1:80,000 in Germany can be
      estimated according to the presented data.

PMID- 9617423
TI  - [Evaluation of malignant hyperthermia episodes with the Clinical Grading Scale].
AB  - PURPOSE: The Clinical Grading Scale (CGS) was introduced to predict malignant
      hyperthermia (MH) susceptibility in adverse anaesthetic events. Because many of
      the clinical symptoms that occur during MH episodes are nonspecific, the CGS was
      designed as a tool to estimate the qualitative likelihood of MH. The purpose of
      this study was to compare the results of the CGS with the established in vitro
      contracture test (IVCT). METHODS: 92 patients with a personal history for MH were
      tested for MH susceptibility with the IVCT according to the protocol of the
      European MH Group. All patients were also evaluated with the CGS. Clinical
      indicators for the CGS are rigidity, muscle breakdown, respiratory acidosis,
      temperature increase and cardiac involvement. There are additional indicators in
      case of a family history for MH. For each indicator 3-15 points are added to
      build a raw score; this raw score corresponds to a MH rank in the CGS that
      describes the likelihood of MH in the suspected event. The higher the raw score
      rank, the higher the likelihood of MH and vice versa. RESULTS: From 92 patients,
      32 (35%) were diagnosed as MH-susceptible (MHS) with the IVCT, 47 (51%) were MH
      normal (MHN), and 13 (14%) were MH-equivocal (MHE). One patient with MH-rank 1
      (MH almost never) in the CGS was diagnosed as MHS; on the other hand no patient
      with MH-rank 6 (MH almost certain) in the CGS was diagnosed as MHN. However, the
      majority of patients (72%) were assigned to ranks 3 and 4 (MH somewhat less than
      likely/MH somewhat greater than likely). The qualitative likelihood of MH could
      therefore not be clearly estimated. CONCLUSION: Our study shows that the MH-rank
      of the CGS corresponds poorly with the results of the IVCT. In any case the
      evaluation of an MH suspicious event depends on the availability of data of that
      event. It is often difficult to obtain sufficient data, especially if the event
      occurred a long while ago. In these cases the MH rank may underestimate the
      likelihood of MH susceptibility. On the other hand, overestimation is also
      possible because some of the scoring indicators depend on the anaesthesiologist's
      judgement only. At present, the use of the CGS is neither validated nor
      clinically feasible. The CGS cannot replace IVCT.

PMID- 9617424
TI  - [Volume substitution with colloids].

PMID- 9617425
TI  - [HES, dextran and gelatin--indications and tolerance].

PMID- 9617426
TI  - [Volume replacement with artifical colloids].

PMID- 9617427
TI  - [Volume therapy in septic shock].

PMID- 9617428
TI  - [Tissue accumulation of synthetic colloids in man].

PMID- 9617429
TI  - [The effect of colloid volume substitution on blood coagulation].

PMID- 9617430
TI  - [The effect of HES, dextran and gelatin on kidney function].

PMID- 9617431
TI  - [Modulation of phagocytosis and endothelial function].

PMID- 9617432
TI  - [Perspectives on small-volume resuscitation].

PMID- 9617433
TI  - [Oxygen-carrying solutions--colloid of the future?].

PMID- 9617434
TI  - [Postoperative apnea].

PMID- 9617435
TI  - Mutations of p16 and p15 tumor suppressor genes and replication errors contribute
      independently to the pathogenesis of sporadic malignant melanoma.
AB  - Mutations of p16 and p15 suppressor oncogenes and the replication errors in six
      microsatellite loci in sporadic malignant melanomas were analyzed. Four (9.1%)
      homozygous deletions of both p16 and p15 genes and one point mutation (2.3%) in
      the p15 gene were detected among 44 primary melanoma samples. One mutation in
      each of the p16 and p15 genes was observed in ten metastatic lesions. Eight
      (18.2%) replication errors were detected in three microsatellite loci in the
      primary melanoma samples, but no replication error was detected in the metastatic
      samples. None of the samples showed the alteration of p16/p15 genes and the
      replication errors concomitantly. These results suggest that (1) the homozygous
      deletions of p16/p15 genes and the replication errors may occur in rather early
      stages of melanoma tumorigenesis, while the p16/p15 gene mutation may occur in
      later stages, and (2) the p16 and p15 gene mutations in sporadic malignant
      melanomas might not be induced by the defect in mismatch repair, implying that
      p16 as well as p15 gene alterations may play an important role in the
      pathogenesis of sporadic malignant melanomas.

PMID- 9617436
TI  - Ehlers-Danlos syndrome type VI: lysyl hydroxylase deficiency due to a novel point
      mutation (W612C).
AB  - Ehlers-Danlos syndrome type VI (EDS VI) is a rare autosomal recessively inherited
      disease of connective tissue. The characteristic symptoms are hyperflexibility of
      joints and hyperelasticity of skin together with marked scoliosis, ocular
      manifestations and involvement of the vascular system. The underlying biochemical
      defect in EDS VI is a deficiency in lysyl hydroxylase (PLOD) activity resulting
      from mutations in the PLOD gene causing a low hydroxylysine content in various
      tissues. We found that two out of three patients showed a recently described
      duplication of about 800 bp in their LH mRNA. In the third patient we identified
      a new point mutation (2036 G-->C) resulting in a substitution of tryptophan by
      cysteine in the highly conserved C-terminal region of the enzyme (W612C). In
      addition, this mutation destroys a restriction site of MwoI. Restriction analysis
      of the patient's cDNA with MwoI showed the sole occurrence of the mutated
      transcript, while one allele in his genomic DNA contained the MwoI restriction
      site. Restriction analysis of the genomic DNA of the unaffected parents displayed
      a heterozygous loss of the restriction site for MwoI in the mother while the DNA
      of the father appeared normal. Our study demonstrates that the new point mutation
      (W612C) in conjunction with a functionless allele, most probably a null allele,
      for the LH gene may explain the functional deficiencies seen in this patient.

PMID- 9617437
TI  - Serum levels of soluble Fas/APO-1 receptor are increased in systemic sclerosis.
AB  - It has been suggested that rheumatic diseases may result from a deficit in Fas
      mediated T-cell apoptosis. Recent studies have demonstrated increased soluble Fas
      in sera from lupus erythematosus patients. We were interested to determine
      whether elevated soluble Fas levels are associated with systemic sclerosis.
      Soluble Fas levels were retrospectively assayed using a sandwich enzyme-linked
      immunosorbent assay in serum from 30 patients with systemic sclerosis and 15
      normal controls. Hospital medical records were retrospectively reviewed for
      clinical and laboratory characteristics of the patients. Soluble Fas levels were
      analysed in subsets of patients with limited (lcSSc) versus diffuse cutaneous
      systemic sclerosis (dcSSc) and correlated with inflammatory activity. In systemic
      sclerosis soluble Fas serum levels (lcSSc, 2.19 +/- 0.71 ng/ml, dcSSc 2.53 +/-
      1.37 ng/ml) were significantly higher than in normal controls (1.26 +/- 0.36
      ng/ml). However, there were no significant differences in soluble Fas levels
      between lcSSc and dcSSc and poor correlation between soluble Fas levels and
      inflammatory activity status. Detection of elevated soluble Fas might serve as a
      clinical marker for immunological dysregulation in systemic sclerosis, but not
      for inflammatory disease activity.

PMID- 9617438
TI  - Regulation of peripheral blood mononuclear cell responses to Dermatophagoides
      farinae by substance P in patients with atopic dermatitis.
AB  - Neuropeptides mediate stress-induced cutaneous inflammation such as atopic
      dermatitis. The effect of substance P on proliferation and cytokine mRNA
      expression of peripheral blood mononuclear cells in response to Dermatophagoides
      farinae (Der f) was studied in atopic dermatitis patients with positive RAST
      scores to Der f. Upon stimulation with Der f peripheral blood mononuclear cells
      from patients proliferated in a B7-dependent (CD80- and CD86-dependent) manner,
      while those from the patients with negative scores, nonatopic eczematous
      dermatitis patients or normal individuals, did not. Based on the reactivity of
      normal individuals, atopic dermatitis patients with a stimulation index greater
      than 1.8 were tentatively defined as high responders, who comprised two-thirds of
      the patients. Proliferation in high responders was associated with upregulation
      of IL-2 mRNA expression and induction of IL-5 mRNA expression. Substance p at 10(
      10) to 10(-8) M promoted the Der f-induced proliferation when added at the start
      of culture and upregulated IL-10 MRNA expression while downregulating IL-5 mRNA
      expression. Our results suggest that substance P modifies immune responses of
      atopic T cells to Der f by promoting proliferation and altering cytokine
      profiles, and thus modulates the clinical manifestations of atopic dermatitis.

PMID- 9617439
TI  - Cutaneous reactions and sensations after intracutaneous injection of vasoactive
      intestinal polypeptide and acetylcholine in atopic eczema patients and healthy
      controls.
AB  - We analysed vasoreactions and sensations of atopic eczema (AE) patients and
      healthy controls after intracutaneous (i.c.) injection of vasoactive intestinal
      polypeptide (VIP) and acetylcholine (ACh). Blood flow was measured by laser
      Doppler flowmetry (LDF). Plasma extravasation and flare size were evaluated
      planimetrically, and sensations were recorded using visual analog scales. Three
      groups of subjects (controls, AE patients suffering from acute eczema and AE
      patients during a symptom-free period) were investigated. We administered VIP
      separately at concentrations of 1.5 x 10(-7), 1.5 x 10(-6) and 1.5 x 10(-5) M and
      in combination with ACh (5.5 x 10(-6) M) into the volar forearm of the subjects.
      Both substances led to an increase in LDF measurements and induced a wheal and
      flare reaction. Blood flow was elevated as a function of dose after a single VIP
      application in all groups. Compared with healthy controls, a significant increase
      in blood flow was measured after combined VIP and ACh administration in AE
      patients suffering from acute AE, whereas flare area and plasma extravasation
      were significantly reduced after single VIP and combined VIP and ACh injections,
      respectively. In all groups, VIP induced dose-dependent pruritus. Compared with a
      control stimulus (0.9% sodium chloride and ACh), combined injections of VIP and
      ACh had no additional effect on the magnitude of the sensation. In AE patients,
      the intensity was similar to that experienced by the control subjects, but the
      quality of sensation was different: ACh induced pain in the control subjects,
      pruritus in AE patients, and a mixture of pain and itching in AE patients showing
      no symptoms. Our results suggest that VIP- and ACh-induced skin reactions and the
      quality of the sensations depend on the activity of the atopic eczema. Confirming
      our former studies, AE patients develop a different quality of sensation after
      ACh administration and also after administration of VIP combined with ACh.
      Therefore, we suggest that ACh might be involved in the pathomechanisms of
      pruritus in AE.

PMID- 9617440
TI  - In vitro effects of retinoids on mitogen-induced peripheral blood leucocyte
      responses.
AB  - The aim of the present study was to investigate the influence of three different
      retinoids, isotretinoin, etretinate and acitretin, on the mitogenic response of
      peripheral blood mononuclear cells (PBMCs) to PHA and PMA in vitro. All three
      retinoids at high concentrations (10(-4)M) significantly inhibited the mitogenic
      response of PBMCs to these mitogens. At lower concentrations (10(-5) M and 10(-6)
      M) none of the three retinoids had any effect on PBMC proliferation in response
      to PHA. Interestingly, isotretinoin and etretinate significantly enhanced the PMA
      induced stimulation of proliferation, whereas acitretin at 10(-5) M failed to
      influence the mitogenic response to PMA but enhanced it at 10(-6) M. The
      enhancing effects of retinoids on the proliferative response of PMA-stimulated
      PBMCs were reversed by rapamycin (10 ng/ml), an immunosuppressant known to
      inhibit the phorbol ester-induced protein kinase C pathway of lymphocyte
      activation. In conclusion, our study indicates that retinoids directly trigger
      the PMA-induced protein kinase C pathway of lymphocyte activation in a
      concentration-dependent manner. This observation could explain the findings of
      previous studies showing an in vivo immunopotentiating effect of retinoids on
      certain immune functions.

PMID- 9617441
TI  - Lipoteichoic acid and protein-A from Staphylococcus aureus stimulate release of
      hepatocyte growth factor (HGF) by human dermal fibroblasts.
AB  - In this study we demonstrated that Staphylococcus aureus lipoteichoic acid (LTA)
      and protein-A (PA) induce the release from human dermal fibroblasts of hepatocyte
      growth factor (HGF), a proliferation factor of epithelial cells (including
      keratinocytes). In contrast, LPS and porins from Pseudomonas aeruginosa did not
      stimulate HGF production. Recombinant human IL-1 beta induced HGF release. This
      production was synergistically enhanced when in association with LTA (by more
      than twice) and PA (by about two-thirds). Controls were performed in the presence
      of bacterial components alone. In previous studies we have shown that LPS and
      porins are inducers of IL-1 alpha and beta and other cytokines from human
      monocytes. Therefore it is possible that in inflammatory cutaneous foci and
      infected wounds, bacterial components may induce HGF release from dermal human
      fibroblasts. LTA and PA act directly, while LPS and porins act indirectly,
      through the release of cytokines by monocytes/macrophages. HGF plays an important
      role in the repair of cutaneous tissue during gram-positive and gram-negative
      infections.

PMID- 9617442
TI  - Barrier recovery is impeded at neutral pH, independent of ionic effects:
      implications for extracellular lipid processing.
AB  - Epidermal permeability barrier homeostasis requires the postsecretory processing
      of polar lipid precursors into nonpolar lipid products within the stratum corneum
      (SC) interstices by a family of lipid hydrolases. A specific requirement for beta
      glucocerebrosidase (beta-GlcCer'ase), which exhibits a distinct acidic pH
      optimum, is particularly well documented. Therefore, we sought to determine
      whether the recovery of the barrier after acute insults requires acidification of
      the SC. We examined permeability barrier recovery by assessing changes in
      transepidermal water loss (TEWL), SC membrane ultrastructure utilizing ruthenium
      tetroxide (RuO4) postfixation, and beta-GlcCer'ase activity by in situ zymography
      at an acidic vs neutral pH. Barrier recovery proceeded normally when acetone
      treated skin was exposed to solutions buffered to an acidic pH. In contrast, the
      initiation of barrier recovery was slowed when treated skin was exposed to
      neutral or alkaline pH, regardless of buffer composition. In addition,
      enhancement of the alkaline buffer-induced delay in barrier recovery occurred
      with Ca2+ and K+ inclusion in the buffer. Moreover, the pH-dependent alteration
      in barrier recovery appeared to occur through a mechanism that was independent of
      Ca(2+)- or K(+)-controlled lamellar body secretion, since both the formation and
      secretion of lamellar bodies proceeded comparably at pH 5.5 and pH 7.4. In
      contrast, exposure to pH 7.4 (but not pH 5.5) resulted in both the persistence of
      immature, extracellular lamellar membrane structures, and a marked decrease in
      the in situ activity of beta-GlcCer'ase. These results suggest first that an
      acidic extracellular pH is necessary for the initiation of barrier recovery, and
      second that the delay in barrier recovery is a consequence of inhibition of
      postsecretory lipid processing.

PMID- 9617443
TI  - N-cadherin expression in human adult T-cell leukemia cell line.

PMID- 9617444
TI  - Distribution of protein 4.1 in basal and squamous cell carcinoma.

PMID- 9617445
TI  - Association between elevated serum antibody levels to streptococcal M12 protein
      and susceptibility to dermatomyositis.

PMID- 9617446
TI  - The pulp capping procedure in primary teeth "revisited".

PMID- 9617447
TI  - Primary incisor restoration using resin-veneered stainless steel crowns.
AB  - The restoration of primary incisors with extensive caries lesions is a clinical
      challenge of severe dimensions. Not only are these teeth difficult to restore,
      but the patient's behavior can affect the treatment negatively. Requirements for
      an acceptable restoration include natural color; durability; adhesive cementation
      that is biocompatible with the pulp; easily and rapidly placed; requires only one
      treatment visit. Compared to other options, stainless steel crowns are the
      easiest to place. The most attractive restoration for these cases today is the
      adhesively bonded resin-composite crown, made by using acetate crown-form
      matrices, but this is being surpassed by the stainless steel crown forms (3M
      Unitek) that can be preveneered. This article describes a step-by-step method of
      placing preveneered stainless steel crowns for primary incisors.

PMID- 9617448
TI  - What if dentists did not treat people with disabilities?

PMID- 9617449
TI  - Eruption cysts: retrospective clinical study of 36 cases.
AB  - The eruption cyst is a lesion associated with an erupting tooth. It appears as a
      transparent, bluish, blue or blue-black swelling of the alveolar mucosa, over a
      temporal or permanent tooth in eruption. The analysis of the thirty-six eruption
      cysts cases studied, corresponding to twenty-seven patients, revealed that their
      most frequent location is in the maxillary permanent dentition, and that they
      mostly occur in a single presentation, and in an age-range of between five and
      nine years. Six cases out of the twenty-seven patients studied showed the
      characteristic of presenting two or more eruption cysts, and in three of these
      cases, the lesions were bilateral, symmetrical and simultaneous. Two other
      patients had been previously diagnosed with cyst diseases. This would suggest
      that, in addition to the possible infection-trauma origin, there is in some cases
      the possibility of a predisponent tendency.

PMID- 9617450
TI  - Have your young pediatric patients been immunized properly?

PMID- 9617451
TI  - Shrinkage stresses associated with incremental composite filling techniques.
AB  - It is commonly accepted that stresses associated with polymerization shrinkage of
      composite restoratives can be reduced by utilization of an incremental filling
      procedure. A recent report using finite element analysis on a simple box
      preparation has shown that such a procedure actually produces higher stresses.
      The purpose of this investigation was to visualize the stresses generated by
      composite resin placed into photoelastic models of two surface preparations using
      different incremental techniques. Primary molar preparations were cast life-sized
      in a photoelastic material. Cavity walls were cleansed, primed and coated with
      unfilled resin. Incremental filling techniques of a hybrid composite resin were
      gingivo-occlusal, oblique, and facio-lingual. Comparisons were made with the bulk
      placement technique. The stresses developed within the model teeth were observed
      in the field of a circular polariscope under magnification. Generally few
      differences in shrinkage-induced stresses, were observed between the incremental
      filling techniques tested. The lowest shrinkage stresses were generated by the
      bulk placement technique.

PMID- 9617452
TI  - Craniofacial changes following early prosthetic treatment in a case of
      hypohidrotic ectodermal dysplasia with complete anodontia.
AB  - The authors describe early prosthetic treatment in a case of hypohidrotic
      ectodermal dysplasia with complete anodontia. Craniofacial changes were analyzed
      by means of Ricketts' cephalometric analysis and superimposition methods. Early
      prosthetic treatment for complete anodontia determined a backward-downward
      rotation of the mandible with consequent normal positioning of the chin in the
      space, normalization in lower facial height, reduction in convexity of the face,
      and improvement in facial esthetics. Superimposition methods demonstrated that
      the direction of growth of both the maxilla and the mandible was progressing
      favorably. Improvements in esthetics and in the function of masticatory and
      perioral muscles, together with their positive psychological impact, were also
      discussed.

PMID- 9617453
TI  - Comparing the behavior of children treated using general anesthesia with those
      treated using conscious sedation.
AB  - This study compared the dental behavior of young children previously treated
      using general anesthesia (GA) with those treated with conscious sedation (CS).
      The sample included healthy children, two to four years of age, treated in
      private practice. The general anesthesia group included twenty-four children
      (mean age at time of treatment = 31 months) who were evaluated twelve to thirty
      six months later (mean = 25 months). The conscious sedation group included thirty
      children (mean age at time of treatment = 35 months) who were evaluated twelve to
      thirty-eight months later (mean = 21 months). Both groups were subjected to a
      standard recall examination during which behavior and anxiety measures were used
      to assess the subjects' responses to the dental setting. Behavior was evaluated
      by the dentist and parent independently. Children were asked about their dental
      fears, recall of previous treatment and willingness to return to the dental
      clinic. Parents were asked to report any suspected psychologic trauma they
      attributed to the previous treatment. Behavior in both groups was positive or
      definitely positive as rated with the Frankl scale in the overwhelming majority
      of subjects (92 percent general anesthesia, 93 percent conscious sedation) as
      evaluated by the dentist. Parents rated their child's behavior more negatively,
      33 percent and 27 percent of the time, respectively, in both groups. Seventeen
      percent of the children reported being afraid of the dentist in the general
      anesthesia group and 20 percent in the conscious sedation group. In both groups,
      fewer than 10 percent of the parents reported that they felt their child was
      traumatized by the initial dental treatment. The results support the hypothesis
      that there is no difference in the expected future dental behavior or anxiety of
      children who experience conscious sedation compared with general anesthesia for
      dental treatment at a young age.

PMID- 9617454
TI  - Attitudes of Hispanic parents toward behavior management techniques.
AB  - The purpose of this study was to evaluate attitudes of parents with Hispanic
      surnames at the University of Texas Health Science Center at San Antonio toward
      various behavior management techniques used in pediatric dentistry. Thirty-two
      parents of pediatric patients who presented for dental treatment were selected at
      random in the Pediatric Dentistry Clinic of the UTHSC-SA. The research study was
      explained to the parent by one dentist from a standardized explanation script.
      Eighty-one percent of the parents had at least a high school education. The
      parents viewed one of two videotapes with a recorded program demonstrating eight
      different behavior management techniques. One tape, shown to half of the parents,
      had a brief explanation and rationale of the specific behavior management
      technique before its demonstration (Group A). The other tape, shown to the
      remainder of the parents, had no explanation before the demonstration of each
      technique (Group B). Following each segment of the tape, the parents indicated
      their degree of accept-ability of the technique, using a visual analogue scale.
      An F-test (0.05 level) and Pearson and Spearman correlation tests were used. The
      results showed that hand-over-mouth (HOM) was unacceptable by 63 percent of the
      parents in Group A and 81 percent in Group B. The papoose board (PB) technique
      was unacceptable in 81 percent in Group A and 63 percent in group B. In both
      groups, parents would prefer to have had the child given general anesthesia
      rather than HOM.

PMID- 9617455
TI  - Early childhood caries and risk factors in rural Puerto Rican children.
AB  - A sample of 167 Puerto Rican children whose ages ranged from six months to forty
      seven months (mean = 23 months) were studied. Children were examined for Early
      Childhood Caries with light and mirror and a structured interview was
      administered to parents and caretakers to identify risk factors. Results
      indicated that only 37.4 percent of the children were free of decalcification
      lesions or frank decay. While 53.9 percent of the children had lesions on
      maxillary incisors, 40.0 percent had molars affected by decalcification lesions
      and caries. Analysis of risk factors indicate that giving the baby a bottle when
      crying at night, number of adults and children in the family, use of fluoridated
      dentifrice, and age of the child were associated with the caries process in these
      children. Bottle and breast feeding, per se, were not risk factors. Disease
      patterns suggest other dietary risk factors, such as frequent snacking on
      food/drinks with sugar.

PMID- 9617456
TI  - Dental findings in Saethre-Chotzen syndrome (acrocephalosyndactyly type III):
      report of case.
AB  - Saethre-Chotzen syndrome is characterized primarily by facial and digital
      anomalies. This case report describes multiple dental anomalies in a patient with
      Saethre-Chotzen, not reported in previous descriptions of the syndrome. These
      features are teeth with broad, bulbous crowns, thin, narrow tapering roots, and
      diffuse pulp stones in the pulp chambers of all posterior teeth. These dental
      findings, along with being associated with the syndrome, may influence dental
      care for these patients.

PMID- 9617457
TI  - Sinus histiocytosis with massive lymphadenopathy: report of case.
AB  - A case of a five-year-old African American female with sinus histiocytosis with
      massive lymphadenopathy is presented. The epidemiology, morbidity, and management
      aspects of this condition are discussed.

PMID- 9617458
TI  - Dentinal dysplasia type I: report of an atypical case in the primary dentition.
AB  - An typical case of dentinal dysplasia type I affecting only the incisors and
      primary first molars is documented. There were no signs of a family heritage or
      signs of the developing permanent dentition being affected precociously.

PMID- 9617460
TI  - Passive immunotherapy in advanced HIV infection and therapeutic plasmapheresis in
      asymptomatic HIV-positive individuals: a four-year clinical experience.
AB  - We have been treating patients with advanced HIV disease using passive
      immunotherapy (PIT). Earlier studies of PIT which have been published concerned
      relatively short periods of treatment: our study is by far the longest and
      reports also on the long-term effects of plasmapheresis on healthy HIV-infected
      individuals. Fifty-nine patients with an average CD4+ T-cell count of 55 per
      cu.mm. at baseline were transfused at monthly intervals with 500 ml of
      hyperimmune plasma. No disease progression or death occurred among the 8
      asymptomatic patients under the treatment, which lasted for 36.25 months on
      average. Seven of the 15 ARC patients progressed to AIDS but none died in an
      average period of 25.9 months. Seven of the 36 symptomatic AIDS patients with
      advanced disease died in an average period of 19.6 months. PIT appears to be
      nontoxic and to have beneficial effects lasting at least four years under
      continuous treatment. It probably delays disease progression in ARC and AIDS
      patients, and almost certainly does so in asymptomatic late HIV infection with a
      very low CD4+ T-cell count. None of the 51 donors suffered adverse effects, nor
      did any progress to ARC or AIDS in an average period of 30.1 months. Their
      laboratory parameters indicated a nearly stable condition: in particular, their
      average CD4+ T-cell count rose from 478 to 498. The study of our plasma donors
      indicated that repeated and frequent plasma donation by asymptomatic HIV-infected
      individuals could delay disease progression, although further studies are needed
      to investigate this.

PMID- 9617459
TI  - Augmentation of the antitumor effect of adoptive immunotherapy by in vivo
      sensitization of EL-4 lymphoma and pre-treatment with sizofiran.
AB  - The antitumor effects of adoptive immunotherapy using LAK cells treated with
      sizofiran (SPG) following in vivo antigen sensitization with EL-4 lymphoma
      (EsLAK), comparing nonsensitized LAK cells (sLAK), were studied in mice with
      intraperitoneal implantation of EL-4 lymphoma. EL-4 cells treated with Mitomycin
      C (100 micrograms/ml) were introduced by inoculation into the peritoneum of
      C57BL/6 mice for antigen sensitization. Four days later, SPG (100 micrograms) was
      intramuscularly injected. Three days after SPG administration, mononuclear cells
      obtained from the spleen were prepared for LAK cells (EsLAK). The following
      results were obtained: 1) The survival period was significantly greater in the
      sLAK and EsLAK groups than in the control group. The survival period in the EsLAK
      group was significantly greater than that in the sLAK group. 2) The number of EL
      4 cells in the peritoneal exudate cells 11 days postimplantation was lowest in
      the EsLAK group, and the number of lymphocytes including LGL was largest in the
      EsLAK group, compared with the sLAK group and the control group. 3) The EsLAK
      cells showed significantly more enhanced cytotoxic activity against EL-4 than the
      sLAK cells. 4) Histopathological findings of metastatic lesions of the liver and
      spleen stained by HE 11 days postimplantation showed less infiltrating tumor
      cells and more lymphocytic infiltrations in the sLAK and EsLAK groups compared
      with the control group. These results suggest that induction of LAK cells by
      administration of SPG to lymphocytes treated by in vivo sensitization with tumor
      antigen increases the efficacy of adoptive immunotherapy.

PMID- 9617461
TI  - Use of recombinant interferon gamma in pediatric patients with advanced juvenile
      chronic arthritis.
AB  - Recombinant interferon (IFN) gamma was used in 10 patients, 6 to 15 years old,
      with juvenile chronic arthritis (JCA) for 5 to 11 years, resistant or with severe
      side effects to other treatments. Six patients had systemic JCA and 4 started as
      pauciarticular. Three of the latter became polyarticular. Treatment schedule was
      50,000 IU-kg daily for 4 weeks, then 3 times per week for 3 months and twice a
      week up to 2 years. Eight cases had favourable clinical response. Prolonged
      steroid regime could be suspended in 7/8 cases who previously received it. Two
      patients with systemic JCA did not respond to IFN treatment. Side effects were
      fever (9), headache (8), chills (6), distal cyanosis, hypotension, leukopenia and
      myalgia (2), and vomiting (1). All were mild or moderate. IFN gamma was more
      tolerable than other drugs and seems to be beneficial for patients with JCA
      resistant to other treatments.

PMID- 9617462
TI  - Effectiveness of weekly subcutaneous recombinant human erythropoietin
      administration for chemotherapy-induced anemia.
AB  - The effects of weekly subcutaneous recombinant human erythropoietin (r-hEPO)
      administration on anemia during chemotherapy including cisplatin and 5
      fluorouracil in patients with head and neck carcinomas were examined. Weekly
      subcutaneous r-hEPO administration in cancer patients has not been investigated
      previously. Patients were treated with r-hEPO 100 IU/kg (2 patients), 200 IU/kg
      (6 patients), or 400 IU/kg (5 patients), or placebo, and effectiveness was
      evaluated by monitoring hemoglobin concentration changes after administration for
      8 weeks. Hemoglobin concentrations in all 3 r-hEPO dosage groups were higher than
      that in the control group during chemotherapy. All r-hEPO doses produced
      improvements in the anemia induced by chemotherapy; however, the 400 IU/kg dose
      was most effective. The requirement for blood transfusions decreased in patients
      receiving r-hEPO therapy, and no significant side-effects were associated with r
      hEPO administration. These results suggest that chemotherapy-induced anemia can
      be prevented by weekly subcutaneous r-hEPO administration.

PMID- 9617463
TI  - Tumor-associated antigens are cytokine inducers and hyporeactivity factors to the
      immune system.
AB  - We investigated possible mechanisms leading to the inhibition of the immune
      system in people with chronic disorders. Tumor cell produce protein released into
      the circulation, such as tumor associated antigens, may play an important role in
      processes preceding paralysis of the immune system. To test this hypothesis the
      following tumor associated antigens were used: AFP, OFP, CA-125, CA-50 and CA-19
      9. Their role was assessed by modulating cytokine production in cord blood
      lymphocytes and peripheral white blood cells obtained from grown population of
      patients treated with colostrinin, an cytokine inducer. PHA, LPS and colostrinin
      were used as positive control in those essays. Each antigen tested individually
      induced IFN, TNF alpha and IL-6 in dose dependent fashion. None of the tested
      cytokines were spontaneously released by the cells. Data generated from these
      experiments indicated that tumor associated antigens are inducing type 1
      cytokines in similar fashion as LPS or colostrinin. However, lymphocytes taken
      from patients undergoing therapy with colostrinin revealed progressive loss
      capability to produce type 1 cytokines as they did in case of colostrinin. The
      loss of the capability to respond to antigen may represent phenomenon leading to
      immune tolerance.

PMID- 9617464
TI  - Oral cavity gate of an entry into the communication network.
AB  - For ages naso-oro-pharyngeal cavity was considered as gate of entry to living
      organism for air and food. In recent years, however, the thoughts have changed
      considerably. Several lines of evidence indicate that the oral cavity with
      adjacent cavities plays a pivotal role for the recognition of signals coming from
      the surrounding world. These signals in form of food, germs, poisonous substances
      are initially analyzed in oral cavity and messages are distributed by a variety
      of communication pathways into pertinent parts of the body. All these diverse
      functions are performed by anatomical structures present in the naso-oro
      pharyngeal cavity. The following article describes some of the functions
      discovered recently.

PMID- 9617465
TI  - High levels of soluble IFN gamma receptor alpha chain in the plasma of rheumatoid
      arthritis patients.
AB  - Soluble receptors for hormones and cytokines have been described. They can serve
      as natural blockers of their respective ligands. The natural soluble interferon
      gamma receptor (sIFN gamma R) has been isolated and characterized only in urine.
      Chromatography of human (hu) plasma from rheumatoid arthritis (RA) patients and
      controls on immobilized hu IFN gamma or antibodies against IFN gamma R alpha
      chain permitted us to isolate the sIFN gamma R. The receptor isolated from one
      control is a protein with a molecular weight between 60-67 kDa depending on the
      presence of reducing agents. We detected a significantly higher level of plasma
      sIFN gamma R in patients with rheumatoid arthritis than in apparently healthy
      subjects.

PMID- 9617466
TI  - The disruption of the 'sense of self' in schizophrenia: potential links with
      disturbances of information processing.
AB  - It is argued in this paper that the disruption of one aspect of the 'sense of
      self' in schizophrenia, that relating to the continuity of conscious experience
      and the organization of action, may be linked to current models of the
      information-processing disturbance prominent in the disorder. The 'sense of self'
      in normal persons in part results from the consistent manner in which
      contextually appropriate stored material operates of sensory input. If, as has
      been proposed, there is in schizophrenia a disruption in the moment-by-moment
      integration of these sources of information, then a disturbance in the 'sense of
      self' is implicit in the cognitive model. A consideration of action
      identification theory (Vallacher & Wegner, 1987) permits further links to be
      made, since higher-level action identities are viewed as being practically
      synonymous with self-defining significance. It is suggested that the information
      processing disturbance results in a tendency to low-level action identification
      and a gradually developing instability in the sense of personal identity.

PMID- 9617467
TI  - Guilt proneness and expressed emotion in relatives of patients with schizophrenia
      or related psychoses.
AB  - OBJECTIVE: Knowledge of what predicts relatives' expressed emotion (EE) may
      contribute to improved family work in schizophrenia. In the present study we
      examined guilt proneness as a determinant of EE components. METHOD: In a
      Norwegian sample of 46 recently hospitalized patients (schizophrenia or
      schizophreniform disorder) and 69 relatives, relatives' expressed emotion was
      assessed by means of the Camberwell Family Interview, and guilt proneness by
      means of the Revised Mosher Guilt Inventory. (RMGI). RESULTS: Confirmatory
      multiple regression analyses showed that hostility-guilt (RMGI) was negatively
      related to high levels of criticism and hostility and, for men, positively
      related to emotional overinvolvement. There was a strong positive relationship
      between relatives' guilty conscience (RMGI) and emotional overinvolvement if the
      patient had a diagnosis of schizophrenia. CONCLUSIONS: Our analyses indicate that
      relatives' guilt proneness may be a determinant of their criticism, hostility and
      emotional overinvolvement towards a schizophrenic family member. This personality
      trait should be taken into account in family work which aims at modifying
      relatives' expressed emotion.

PMID- 9617468
TI  - Denial and its reasoning.
AB  - This work is aimed at analysing the motivated reasoning underlying denial of some
      piece of information. Denial is first distinguished from both repression and
      biased interpretation; then an analysis is provided of the reasoning devices
      typical of denial. The rules on which reasoned denial is based are similar to
      those governing the individual's normal cognitive activity. Reasoned denial is
      here represented in the form of if-then implications, where the to-be-denied
      belief plays the role of a consequence drawn from a given premise. So, in order
      to deny such a consequence one may either deny its premise, or search an
      alternative consequence, or search an alternative premise, or deny the very
      relation of implication, and so on. Each type of reasoning is logically biased,
      while at the same time psychologically plausible and convincing. A typical
      feature shared by all the reasoning strategies considered is the identification
      of 'unproven' with 'false'.

PMID- 9617469
TI  - Understanding patients: implicit personality theory and the general practitioner.
AB  - The patient-centred general practitioner (GP) is expected to advance beyond
      biomedical illness categorization (the disease-centred method) and develop an
      understanding of the 'whole person' in order to inform clinical decision making.
      This paper argues that researchers cannot yet provide GPs with a relevant,
      reliable and predictive model of individual behaviour that would apply
      unproblematically to their everyday clinical work. Without such a system, it is
      hypothesized that GPs will continue to use their own implicit personality
      theories and models of human behaviour in their attempts to understand and
      predict patient behaviour. Research into such theories from a variety of
      perspectives could illuminate their content, structure, validity and function in
      general practice.

PMID- 9617470
TI  - Personality disorders in pulmonary patients.
AB  - A sample of 59 patients with asthma and chronic obstructive pulmonary diseases
      (COPD) was compared to matched samples of psychiatric patients and normal
      individuals with respect to personality disorders (PDs) assessed by a self-report
      measure (VKP) (Duijsens, Eurelings-Bontekoe, Diekstra & Ouwersloot, 1993a, b).
      The number of PDs differed significantly between pulmonary and psychiatric
      patients, while there was no significant difference between pulmonary patients
      and normal individuals. Comparison of the number of diagnosis criteria yielded
      significant contrasts between psychiatric patients versus the normal individuals
      and the pulmonary patients. Pulmonary patients and normal individuals showed
      significantly lower mean number of criteria met than matched psychiatric patients
      for nearly all of the diagnoses. It is concluded that PDs are no more prevalent
      in asthma and COPD patients than in the general population.

PMID- 9617471
TI  - Subjective body-image dimensions in normal and anorexic adolescents.
AB  - The subjective body dimensions of adolescent anorexic patients and adolescents
      from the general population were studied by means of a new technique that
      combines certain characteristics of the 'body-site estimation' and the 'whole
      image adjustment' procedures. The technique used (Subjective Body Dimensions
      Apparatus-SBDA) reveals the individual's idea of the size of the different parts
      of his/her body, and produces a life-size global silhouette. Eighty-five female
      anorexic patients (ages 12 to 18) were compared with 427 adolescents from the
      general population. The technique showed acceptable test-retest stability. The
      comparison group overestimated their thorax, waist and hips, and anorexic
      patients overestimated all parts of their body but their thorax, waist and hips
      especially. For all parts of the body, the anorexic group showed greater
      overestimation (p < .0001) than the comparison group.

PMID- 9617472
TI  - The role of anxiety and depression in fatigue and patterns of pain among
      subgroups of fibromyalgia patients.
AB  - This study explored the relationship of anxiety and depression with two major
      symptoms of fibromyalgia, pain and fatigue, among fibromyalgia patients (N =
      322). Due to collinearity between anxiety and depression scores, extreme groups
      were defined according to high versus low anxiety and depression scores. Two
      thirds of the initial sample were excluded by this approach, which permitted a
      two by two factorial split-plot ANOVA for the assessment of main effects and the
      interaction of anxiety and depression upon pain and fatigue. Results stated
      independent, additive, effects of anxiety and depression upon levels of pain and
      fatigue, whereas interaction between anxiety and depression failed to
      significantly explain symptom differences among the participants. Correlational
      analyses indicated widespread pain among the low anxiety subgroups. In contrast,
      widespread pain was not indicated among anxious patients with low scores on
      depression. The findings support the hypothesis that (1) anxiety and depression
      are independently associated with severity of pain symptoms in fibromyalgia, and
      that (2) patients with high anxiety and low depression may communicate to the
      medical doctor in ways that involve a risk of diagnosing fibromyalgia when the
      criterion of widespread pain is not supported. These conclusions were confirmed
      by results from ANCOVAs that permitted more extensive control of collinearity
      among variables.

PMID- 9617473
TI  - Oral pessimism and depressive symptoms: a comparison with other correlates of
      depression.
AB  - The need to examine alternative explanations for findings in psychoanalytic
      theory is often suggested but rarely practised. The aim of the present study was
      to examine Lewis' (1993) prediction that oral pessimism is important to the
      aetiology of depression within the context of social psychological, cognitive and
      personality explanations of depression. One hundred and sixty Northern Irish
      university students completed measures of depressive symptoms, oral pessimism and
      oral optimism, optimism, neuroticism, coping style, attribution style and self
      esteem. Results show that oral pessimism, neuroticism and the use of stable
      attributions are dominant in accounting for variance in a measure of depression
      and support Lewis' (1993) finding that oral pessimism is important in depressive
      symptoms.

PMID- 9617474
TI  - Functional modification of proteins of the nervous system by pyridoxal 5'
      phosphate.

PMID- 9617475
TI  - Autocrine/paracrine activator of cell proliferation: purification of a 4-6 kD
      compound with growth-factor-like effects in Tetrahymena thermophila.
AB  - Extracellular medium from cultures of Tetrahymena thermophila was collected,
      concentrated and fractionated by ultrafiltration and low-pressure column
      chromatography. The effect on proliferation of various fractions was tested on
      cultures of T. thermophila in synthetic medium at low initial cell densities (<
      250 cells/ml). In unsupplemented cultures, cells failed to thrive and died before
      proliferation. Addition of the fraction isolated from the extracellular medium in
      the molecular weight range of 1-10 kD activated the cells to proliferate. The
      size of the main compound in this fraction, herein referred to as TPAF, was in
      the range of 4-6 kD as estimated by SDS-PAGE. Evidence of a dialysable factor
      produced by cells in the stationary phase inhibiting cell proliferation has also
      been found.

PMID- 9617476
TI  - pH regulation in sensitive and multidrug resistant Ehrlich ascites tumor cells.
AB  - Maintenance and regulation of intracellular pH (pHi) was studied in wild-type
      Ehrlich ascites tumor cells (EHR2) and five progressively daunorubicin-resistant,
      P-glycoprotein (P-gp)-expressing strains, the maximally resistant of which is
      EHR2/1.3. Steady-state pHi was similar in cells expressing different amounts of P
      gp, in the absence and presence of glucose. In EHR2/1.3, glucose-induced
      acidification was reduced, and proton efflux was increased, compared to the wild
      type EHR2, differences which were not caused by increased activity of a Na+/H+
      exchanger in the resistant cells. Comparing all six cell lines, no evidence was
      found for a correlation between the amount of P-gp in the membrane and pHi
      regulation, which was also unaffected by P-gp modulators. However, a correlation
      was seen between relative resistance/daunorubicin accumulation and acid extrusion
      rate, which is likely to be due to aspects of development of drug resistance
      other than P-gp.

PMID- 9617477
TI  - Cl/HCO3 antiport affects H-lactate symport activity at the basolateral pole of
      jejunum enterocyte.
AB  - BACKGROUND/AIMS: Under normal conditions the jejunal tract of the rat intestine
      absorbs HCO3. A basolateral Cl/HCO3 exchange, evidenced by means of membrane
      vesicles, could be involved in this process. Aim of this study was to investigate
      the anion exchange activity in the whole jejunal tract, where various transport
      systems could interact. METHODS: In the jejunal tract of rat intestine everted
      and incubated in vitro, the experimental conditions set up minimized loss of CO2
      from the serosal solution, where pH and pCO2 were determined together with fluid
      and electrolyte transintestinal transport. RESULTS: The serosal pCO2 increase and
      pH decrease, evident during the experiment, could be antagonized by enhancing the
      4,4-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) concentrations in the
      serosal fluid. Moreover high DIDS concentration affected fluid, sodium, lactate,
      bicarbonate and, although in the opposite direction, chloride transport, whilst
      they were ineffective on K flux. CONCLUSION: These results give evidence that in
      the basolateral membrane the inhibition of Cl/HCO3 antiport causes a diminution
      of lactic acid movement. Therefore we can hypothesize that Cl/HCO3 antiport
      facilitates basolateral H-lactate symport in order to carry endogenous lactic
      acid towards the blood stream.

PMID- 9617478
TI  - Mag-Fura-2 (Furaptra) exhibits both low (microM) and high (nM) affinity for Ca2+.
AB  - Based on studies using high-affinity Ca2+ probes (dissociation constant (Kd) =
      0.15-0.3 microM), steady-state [Ca2+]in is believed to be in the nanomolar range
      in most cells. However, probes with lower affinity indicate that [Ca2+]in may
      increase to micromolar levels during activation of specific cell functions, e.g.,
      contraction. These conclusions rely on accurate knowledge of the Kd of the dyes
      for Ca2+. Mag-Fura-2 (also known as Furaptra) is a low-affinity Ca2+ indicator
      (Kd ca. 50 microM) which has been used for such studies. In the present work, Mag
      Fura-2 is shown to respond to changes in cytosolic Ca2+ in the submicromolar
      range. In vitro, and in situ titration of Mag-Fura-2 in A7r5 cells, demonstrate
      that Mag-Fura-2 exhibits both high- and low-affinity for Ca2+. Moreover, pH
      affects both high and low affinity Ca2+ binding site. Since Mag-Fura-2 has been
      used to study Ca2+ within specific subcellular compartments, the present
      observations indicate that knowledge of factors such as ambient pH of these
      compartments is required to accurately interpret Ca2+ responses. Furthermore, the
      sensitivity of Mag-Fura-2 at submicromolar levels must be considered for accurate
      determination of Ca2+ in specific compartments believed to exhibit high
      micromolar levels of Ca2+.

PMID- 9617479
TI  - Protein kinase C and the cytoskeleton.
AB  - The protein kinase C family of serine-threonine kinases are important signal
      transducers participating in many different agonist-induced signalling cascades.
      PKC is activated by increases in diacylglycerol produced in response to agonist
      induced hydrolysis of inositol phospholipids. PKC is thought to reside in the
      cytosol in an inactive conformation and translocate to the plasma membrane upon
      cell activation where it modifies various cellular functions through
      phosphorylation of target substrates. Increasing evidence has illustrated that
      this family of enzymes is capable of translocating to other subcellular sites
      than the plasma membrane. A key to understanding the functions of the members of
      this family is identifying their physiological substrates and their relationship
      with those target substrates. The idea that PKC may be an important regulator of
      cytoskeletal function has been suggested by numerous studies. Activation of PKC
      in a variety of different cell types leads to changes in the cell cytoskeleton
      including lymphocyte surface receptor capping, smooth muscle contraction and
      actin rearrangement in T cells and neutrophils. Given the ubiquitous expression
      of PKC and the diversity of cytoskeletons in different cell types it is not
      surprising that PKC has been shown to be associated with and/or phosphorylate a
      wide range of cytoskeletal components. This review examines the interaction of
      PKC with the cytoskeleton and discusses some of the cytoskeletal functions
      ascribed to PKC to date.

PMID- 9617480
TI  - Downstream signalling events regulated by phosphatidylinositol 3-kinase activity.
AB  - The phosphatidylinositol (PI) 3-kinase family of enzymes is now known to be
      regulated by several different upstream pathways in response to virtually all
      growth factors and cytokines. In the past few years, the phosphoinositides
      phosphorylated at the 3-OH position of the inositol ring have been shown to be
      lipid second messengers that may directly or indirectly regulate the activity of
      several different serine/threonine kinases. Consistent with the many different
      cellular events in which PI 3-kinase plays an important role, a diverse group of
      serine/threonine kinases are regulated downstream of PI 3-kinases, including
      protein kinase C (PKC) isoforms, p70 S6 kinase, and PKB/Akt. This review
      summarises studies done primarily in the past few years that have begun to
      unravel these targets of PI 3-kinase activity.

PMID- 9617481
TI  - Differential mitogenic actions of alpha 1- and beta-adrenergic agonists on rat
      hepatocytes.
AB  - alpha 1-Adrenergic receptor-mediated responses are overwhelming in adult rat
      hepatocytes. Inversely, beta-responses are predominant over alpha 1-responses in
      the hepatocytes that have been cultured at a low cell density (10(4) cells/cm2)
      for 24 h. The insulin-EGF-induced DNA synthesis in the beta-response-dominant
      hepatocytes was doubled by beta-agonists or cAMP-generating agents added far
      behind (16-20 h) the addition of insulin/EGF; i.e., immediately before the entry
      into the S-phase of the cell cycle. Agonists of alpha 1-adrenergic or other Ca2+,
      mobilising receptors added to the alpha 1-response-dominant hepatocytes increased
      DNA synthesis only if they were added within 1-2 h after the addition of
      insulin/EGF, at the early stage of G1-phase. Agonists of "non-dominant" receptors
      were rather antagonistic to agonists of "dominant" receptors. Thus, agonists of
      alpha 1-adrenergic (and other Ca2+ mobilising) receptors and agonists of beta
      adrenergic (and other cAMP-generating) receptors acted as comitogens in their own
      particular manners in the presence of growth factors in hepatocytes in which the
      respective receptor functions were dominant.

PMID- 9617482
TI  - Role of nitric oxide in cardiac beta-adrenoceptor-inotropic response.
AB  - We examined some of the signalling events in the negative modulation of
      isoproterenol-induced stimulation of contractility in rat isolated atria.
      Isoproterenol-mediated positive inotropic response is accompanied by the
      stimulation of nitric oxide synthase (NOS) and an increase in the production of
      cyclic GMP (cGMP). Inhibition of NOS and guanylate cyclase increased the dose
      response curve of isoproterenol on contractility. Inhibitors of calcium flux or
      calcium calmodulin, but not of protein kinase C, abrogated these mechanisms. The
      existence of a modulatory negative inotropic-cyclic GMP-mediated mechanism
      limiting the effect of beta-adrenergic stimulation in myocardium is discussed.

PMID- 9617483
TI  - Effects of protein kinase inhibitors on heat-induced hsp72 gene expression in a
      human glioblastoma cell line.
AB  - We examined the effects of several kinds of protein kinase inhibitors against
      calcium/phospholipid-dependent protein kinase (PKC) and cAMP-dependent protein
      kinase (PKA) on heat-induced hsp72 gene expression in a human glioblastoma cell
      line (T98G) as a source of insight into the type of protein kinase contributing
      to its gene expression. When the cells were treated with 1-(5
      isoquinolinesulphonyl)-2-methylpiperazine [(H7) a potent inhibitor of PKC, PKA,
      and others], the suppression of heat-induced Hsp72 accumulation was observed.
      Heat-induced Hsp72 accumulation was also suppressed by staurosporine (a potent
      inhibitor of PKC and PKA) or calphostin C [(CAL) a potent inhibitor of PKC] at
      high concentration (10 x IC50) but not at low concentration (1 x IC50). N-(2-(p
      Bromocinnamylamino)ethyl]-5-isoquinolinesulphonamide [(H89) a potent inhibitor of
      PKA] did not affect heat-induced Hsp72 accumulation at either low (1 x IC50) or
      high concentrations (10 x IC50). Combination treatment with CAL and H89
      suppressed the heat-induced Hsp72 accumulation more strongly than did treatment
      with either inhibitor alone. Furthermore, the heat-induced DNA-binding activation
      of heat-shock factor (HSF) was suppressed by CAL at high concentration (10 x
      IC50), and combination treatment with CAL and H89 showed stronger suppression. In
      the H7 treatment, the clear suppression of HSF activation was observed even at
      low concentration (1 x IC50). In addition, the cellular content of Hsp72
      increased after the treatment of PKC or PKA activator. These results suggest that
      not only PKC, but also PKA may play an important role in heat-induced hsp72 gene
      expression.

PMID- 9617484
TI  - Delta-protein kinase C phosphorylation parallels inhibition of nerve growth
      factor-induced differentiation independent of changes in Trk A and MAP kinase
      signalling in PC12 cells.
AB  - We investigated the ability of bryostatin 1 to block nerve growth factor (NGF)
      induced differentiation of pheochromocytoma PC12 cells and to effect expression
      of protein kinase C (PKC) isoforms. Compared with phorbol myristate acetate
      (PMA), a likewise potent activator of PKC, high doses of bryostatin (> 200 nM)
      failed to down-regulate delta-PKC, as with zeta-PKC, whereas, alpha-PKC was
      completely down-regulated. Two forms of delta-PKC were expressed in PC12 cells, a
      phosphorylated 78.000 M(r) species and a de-phosphorylated 76.000 M(r) form. High
      dose bryostatin treatment resulted in a 4.5-fold increase in phosphorylated delta
      PKC and a 2.5-fold increase in phosphotyrosine. Inhibition of tyrosine kinase
      activity, with either herbimycin or genistein, prior to addition of bryostatin
      abrogated protection from down-regulation and led to simultaneous increases in
      ubiquitinated 110.000 M(r)-delta-PKC. Similarly, pre-treatment of cells with N
      acetyl-L-leucinyl-L-leucinyl-L-norleucinal, an inhibitor of the proteasome
      pathway, prior to low-dose treatment with bryostatin resulted in a dose-dependent
      accumulation of delta-PKC and inhibition of down-regulation. Protection of delta
      PKC from down-regulation by high-dose bryostatin requires a counter-balance
      between protein tyrosine kinase and phosphatase systems. High doses of bryostatin
      blocked NGF-induced neurite outgrowth without altering Y-490 TrK A
      phosphorylation or an alteration in pp44/42 mitogen-activated protein kinase. Our
      findings suggest that the phosphorylation state of delta-PKC may regulate its
      ability to participate in signal coupling and modulation of cell growth and
      differentiation pathways. Moreover, these data reveal the existence of a
      signalling pathway independent of MAP kinase that affects NGF differentiation in
      a negative fashion.

PMID- 9617485
TI  - A somatostatin analogue induces translocation of Ku 86 autoantigen from the
      cytosol to the nucleus in colon tumour cells.
AB  - Flow cytometric and electron microscopic immunocytochemical studies have been
      performed in HT-29 human colon tumour cells in vitro, to determine and localise
      p86 Ku protein, which is a regulatory subunit of DNA-dependent kinase and a
      specific binding site for somatostatin. We have demonstrated that HT-29 cells
      contain p86 Ku and that the distribution between the cytoplasm and the nucleus is
      even. After administration of the somatostatin analogues Sandostatin and TT-232
      to HT-29 cells, the p86 Ku content of the cytoplasmic compartment decreased in
      the first 4 h. An increase in the content of this protein in the nuclear
      compartment was observed at hour 1 followed by a decrease at hour 4 after
      treatment. Quantitative differences between the two analogues have been observed
      in this respect. The practical significance of these findings is discussed.

PMID- 9617486
TI  - Constitutive association of EGF receptor with the CrkII-23 mutant that inhibits
      transformation of NRK cells by EGF and TGF-beta.
AB  - Crk belongs to the adapter proteins that participate in many signalling pathways
      from cell surface receptors. We have characterised the CrkII-23 mutant that
      inhibits the transformation of NRK cells induced by epidermal growth factor (EGF)
      and transforming growth factor (TGF)-beta. To study the biochemical difference,
      cDNAs of the wild-type CrkII and the CrkII-23 mutant were introduced stably into
      NIH 3T3 cells expressing EGF receptor (EGFR). Both CrkII and CrkII-23 were
      phosphorylated on tyrosine upon EGF simulation with similar time course and dose
      dependency. Whereas the wild-type CrkII bound to EGFR only after EGF stimulation,
      CrkII-23 bound to EGFR from before stimulation. Mutation in the Src homology (SH)
      2 or amino-terminal SH3 domain did not abolish the binding of CrkII-23 to EGFR in
      the quiescent cells, suggesting that the binding is mediated by a novel
      mechanism. These CrkII-23-derived mutants, however, did not suppress
      transformation of NRK cells by EGF and TGF-beta. Hence, both the SH2 and amino
      terminal SH3 domains are required to inhibit transformation of NRK cells. These
      results suggest that persistent signalling from CrkII-23 bound to EGFR suppresses
      transformation by EGF and TGF-beta in NRK23 cells.

PMID- 9617487
TI  - Comparison of the changes in protein kinase C induced by glutamate in primary
      cortical neurons and by in vivo cerebral ischaemia.
AB  - Changes in protein kinase C (PKC) were compared in primary cortical neurons
      exposed to glutamate and in the CA-1 hippocampal region of rats subjected to
      transient cerebral ischaemia. After a 15-min exposure of cortical neurons to
      excitotoxic levels of glutamate, a 50-60% loss of membrane PKC activity but only
      about a 20% loss in the amount of enzyme was observed, suggesting that in
      addition to enzyme loss other mechanisms also contributed to the overall loss of
      membrane PKC activity. Glutamate induced a 25-40% decrease in immunodetectable
      levels of PKC alpha, beta, gamma, and lambda but no detectable changes in PCK
      epsilon and zeta. The loss of PKC activity coincided with a shift in
      electrophoretic mobility of PKC gamma, epsilon, and lambda, but not of PKC alpha,
      beta, or zeta, suggesting post-translational modification of some PKC isoforms.
      By comparison, in rats subjected to transient (15-min) global ischaemia, a
      similar 50-60% decrease in membrane PKC activity, a 20-25% loss in the amount of
      PKC, and a shift in PKC mobility were observed in CA-1 neurons 6 h post
      reperfusion. In both the in vivo and the in vitro "ischaemic" models,
      administration of the AMPA receptor antagonist NBQX prevented the loss of PKC
      activity. These results indicate that the loss of PKC observed in in vivo
      ischaemia is likely to be due to excitotoxic damage and that this event can be
      closely mirrored in primary neuronal cultures damaged by glutamate.

PMID- 9617489
TI  - Renal angiomyolipoma: optimal treatment based on size and symptoms.
AB  - The natural history of renal angiomyolipoma is not well delineated. Current
      management options include observation, embolization, and partial or total
      nephrectomy. Recommendations for treatment are usually based on the patient's
      symptoms or the size of the lesion. In an effort to help define the optimal
      treatment of renal angiomyolipomas, we reviewed our experience over the last 10
      years with these tumors. We performed a retrospective study of 37 patients (48
      renal units) diagnosed with renal angiomyolipoma over a ten year period at our
      medical center (mean follow-up 40 months, range 1 month-12 years). Lesions were
      classified as small (< 4 cm), medium (4-8 cm) or large (> 8 cm) based on the
      single largest lesion in each kidney. The relationship between the size, symptoms
      and treatment was reviewed. Patients were also analyzed with regard to the
      diagnosis of tuberous sclerosis. Our findings indicate renal angiomyolipomas less
      than 4 cm (21/37 patients) tend to be asymptomatic and generally do not require
      intervention. Angiomyolipomas greater than 8 cm were responsible for significant
      morbidity and generally require treatment (5/6). Patients with tuberous sclerosis
      made up one half (3/6) of the large lesions. Medium-sized lesions had a less
      predictable natural history, with 54% (7/13) requiring intervention to treat
      hemorrhagic complications. Small asymptomatic lesions (< 4 cm) tend to remain
      stable but should be periodically evaluated. Medium-sized lesions (4-8 cm) have
      the most variable behavior. These lesions should be followed closely with serial
      imaging studies, and if significant changes in size or symptoms are noted, or the
      patient is at risk for flank trauma, elective intervention should be initiated
      promptly to increase the chances of renal salvage. Large asymptomatic
      angiomyolipomas (> 8 cm) will most likely become symptomatic and should be
      treated electively prior to the development of symptoms and potential
      complications.

PMID- 9617488
TI  - Immunohistochemical study of human advanced glycation end-products (AGE) and
      growth factors in cardiac tissues of patients on maintenance dialysis and with
      kidney transplantation.
AB  - Cardiovascular disease is one of the most common complications of dialysis and
      renal transplant patients, and high levels of AGE are present in end-stage renal
      failure. To address the potential involvement of AGE and growth factors in the
      pathophysiology of cardiovascular complications, we performed immunostaining
      using cardiac tissues from autopsy cases of patients on maintenance dialysis (10
      cases), long-term surviving renal transplant patients with functioning grafts (8
      cases), control subjects with normal renal function (7 cases) and non diabetic
      subjects with mild renal insufficiency (8 cases). We used two types of AGE
      antibodies, 6D12 [monoclonal anti-AGE antibody, recognizing N epsilon
      (carboxymethyl) lysine(CML)-modified AGE] (oxidative AGE) and non-CML-PA
      [polyclonal, not recognizing CML], and antibodies against PDGFs, PDGF receptors
      and TGF beta. Positive 6D12 staining was observed in the coronary arterial walls
      and in macrophages. The accumulation of 6D12-reactive AGE in the coronary
      arterial walls of maintenance dialysis patients was significantly greater than
      that of control subjects (p < 0.05). Renal transplantation significantly reduced
      this accumulation (p < 0.05). On the other hand non-CML-PA mainly detected AGE in
      intracardiac arterioles and neural tissues. There was little difference in the
      accumulation of non-CML-AGE among the four groups. PDGFs and PDGF receptors were
      mainly detected in vascular endothelial cells and infiltrating cells of cardiac
      tissues of renal transplant patients, but not of maintenance dialysis patients.
      TGF beta was not detected in cardiovascular tissue of transplant patients. Our
      results indicated that the accumulation of oxidative AGE (CML-AGE) in the cardiac
      vascular tissue is one of the factors for cardiovascular complications of
      maintenance dialysis patients, and also that renal transplantation has a reducing
      effect on CML-AGE accumulation. PDGFs may be involved in the cardiovascular
      complications after renal transplantation.

PMID- 9617490
TI  - Variations in plasma sodium concentration in post-operative patients depend on an
      electrolyte-free water balance, part of a tonicity balance.
AB  - BACKGROUND: There is an inverse relationship between changes in the concentration
      of sodium in plasma (PNa) and intracellular fluid (ICF) volume. Intakes and
      losses of sodium (Na), potassium (K) and water can be divided into two volumes:
      isotonic and electrolyte-free water (EFW). Calculations of these volumes assess a
      tonicity balance, a tonicity imbalance results in a change of PNa: when EFW is
      added to body fluids, PNa decreases. Moreover, the concept of EFW permits a good
      understanding of the renal contribution to the defence of body tonicity. PURPOSE:
      To illustrate that the measurement of a tonicity balance provides the best
      estimate of changes in PNa in an ICU setting. METHODS: Twenty-two patients were
      admitted to the Post-Operative Intensive Care Unit. We investigated how well
      changes in EFW balance correlated with PNa variations and what is the best
      formula to calculate EFW in this setting. RESULTS: PNa changes depend on EFW
      balance; there is no significant relationship with other classical factors such
      as urinary osmolality or Na-free water. CONCLUSION: The utility of a tonicity
      balance is demonstrated. A formula is derived facilitating at the bedside the
      prediction of changes in PNa following fluid therapy: PNa2 = [(PNa1.TBW) +
      balance (Na + K)]/[TBW + balance H2O]. PNa changes can be understood and/or
      modified exclusively by a careful measurement of intakes and losses of Na, K and
      water.

PMID- 9617491
TI  - Care in the use of ibuprofen as an antipyretic in children.
AB  - Ibuprofen is being widely used as an antipyretic in children. Recent studies
      indicate that it is as efficacious and with no significant difference in side
      effects when compared to paracetamol. We describe three cases that illustrate
      that renal complications can occur when ibuprofen is prescribed in the presence
      of intravascular volume depletion and/or pre-existing renal problems. We discuss
      the mode of action of ibuprofen and recommend that its use as an antiypretic in
      children should be avoided in actual or potential intravascular volume
      contraction and in cases with pre-existing renal problems.

PMID- 9617493
TI  - Impairment of methylamine clearance in uremic patients and its nephropathological
      implications.
AB  - The urinary levels of methylamine were analyzed by an HPLC/fluorometric method
      following derivatization of the amine with O-phthaldialdehyde (OPA). The
      excretion of methylamine in the uremic patients was found to be dramatically
      reduced. The impairment of clearance of methylamine explains why this amine was
      substantially increased in the serum of uremic patients. Increased deamination of
      methylamine would enhance formaldehyde and oxidative stresses, i.e. in the blood
      vessels, and cause vascular damage. This may be related to the increased risk of
      angiopathy associated with renal failure, and accelerate the progression of renal
      failure.

PMID- 9617492
TI  - Serum ferritin levels are increased in patients with acute renal failure.
AB  - After having observed high serum ferritin concentrations in some patients with
      acute renal failure (ARF) we decided to evaluate serum ferritin and iron levels
      in patients with acute and chronic renal failure (CRF). The concentrations of
      BUN, serum creatinine, Hct, Hb, serum iron and serum ferritin were measured in 47
      patients with renal failure who were divided into two groups (A and B). Group A
      included 24 patients with ARF (19 M, 5 F) and group B 23 patients with CRF (12 M,
      11 F). The diagnosis of ARF or CRF was based on patients' history and clinical
      examination and confirmed by the standard laboratory findings and the subsequent
      clinical outcome. None of the patients had received iron, blood transfusions or
      erythropoietin during the last six months and none had malignancy or primary
      liver diseases. As controls were used 20 normal volunteers (group C) and 10
      patients with acute infections (group D). Comparing groups A and B we did not
      found any difference in BUN, creatinine and serum iron levels. However patients
      in group A had significantly higher serum ferritin levels (1000 +/- 752 vs 90 +/-
      56 ng/dl, p = 0.0001), higher Hct (31.8 +/- 4.4 vs 25.3 +/- 4.1%, p = 0.0001) and
      higher Hb concentrations (10.5 +/- 1.7 vs 8.1 +/- 1.4 g/dl, p = 0.0001). Ferritin
      levels in patients with ARF were also higher than the corresponding levels of
      normal controls (group C) (p = 0.0001), but did not differ significantly from
      those measured in patients with acute infection (group D). We conclude that in
      patients with acute renal failure serum ferritin levels are increased and do not
      reflect serum iron levels.

PMID- 9617494
TI  - Relationship between serum parathyroid hormone levels and lipid profile in
      hemodialysis patients. Evolution of lipid parameters after parathyroidectomy.
AB  - To determine the influence of parathyroid hormone (PTH) on lipid disturbances of
      uremia, the lipid profile was determined in 34 hemodialysis (HD) patients,
      comparing lipid parameters among subjects classified according to their intact
      PTH level. Furthermore, the effect of correction of severe secondary
      hyperparathyroidism on serum lipids was evaluated in 7 patients after
      parathyroidectomy. Total cholesterol, high-density lipoproteins (HDL),
      triglycerides, apolipoproteins A-I and B-100 (Apo B and Apo B), lipoprotein(a)
      and the ratios of cholesterol/HDL and Apo A/Apo B were analyzed. There was no
      correlation between serum lipids and PTH levels in the total group. Lipid profile
      was similar among patients classified according to their PTH level. No
      correlations were observed in either group between lipids and PTH. Lipid profile
      did not change in the seven patients with severe secondary hyperparathyroidism
      after parathyroidectomy. In conclusion, there was no relationship between PTH and
      lipids and risk ratios in HD patients. Lipid profile did not change in patients
      with severe secondary hyperparathyroidism after parathyroidectomy. These findings
      suggest that PTH does not play a significant role in the dyslipidemia of renal
      failure.

PMID- 9617495
TI  - Echocardiographic evaluation in long-term continuous ambulatory peritoneal
      dialysis compared with the hemodialysis patients.
AB  - In dialysis patients, the prevalence of severe left ventricular (LV) hypertrophy
      and systolic failure, important predictors of cardiovascular morbidity and
      mortality, has been reported to be very high. Therefore, we investigated cardiac
      function in 17 long-term CAPD patients (dialysis duration: 76.5 +/- 13.2 months;
      L-CAPD) by echocardiography and pulsed Doppler, and then compared with 16 short
      term CAPD patients (dialysis duration: 28.9 +/- 11.9 months; S-CAPD), 21 long
      term hemodialysis patients (dialysis duration: 165.1 +/- 52.7 months; L-HD), and
      22 short-term hemodialysis patients (dialysis duration: 71.3 +/- 28.9 months; S
      HD), except for the cases with diabetes mellitus, ischemic heart disease, cardiac
      surgery or overt congestive heart failure. We selected 13 normotensive patients
      with normal kidney function as normal control group matched for sex and age
      (Control). Concerning with L-CAPD, S-CAPD, L-HD, and S-HD, these four groups were
      matched for age and original diseases. We examined blood pressure (BP),
      cardiothoracic rate (CTR), antihypertensive (AHT) drugs and laboratory data. Wall
      thickness, left atrium, ventricular chamber size, ejection fraction (EF) and left
      ventricular mass (LV mass) [Devereux et al. 1986] were measured by
      echocardiograph. Peak early diastolic flow velocity (E), peak atrial filling
      velocity (A), A/E ratio and deceleration time of peak early diastolic flow
      velocity (DT) were calculated by analyzing transmitral flow, recorded by pulsed
      Doppler. BP control, CTR and EF were significantly worse in L-CAPD than in other
      patient groups. A/E as one of parameters for cardiac diastolic function was
      significantly higher in L-CAPD than in HD patients. LVMI (LV mass index: LV
      mass/body surface area) was significantly higher in L-CAPD than in other groups.
      LVMI in CAPD patients was shown to be significantly worse as time goes. Volume
      control by itself without AHT drugs could achieve good BP control in the long
      term CAPD patients who were changed to maintenance hemodialysis because of
      peritoneal sclerosis. We concluded that LV hypertrophy and systolic dysfunction
      tend to progress in CAPD patients as time goes on. Also it is suggested that the
      cause of cardiac dysfunction in CAPD patients was mainly based on poor BP control
      probably due to overhydration, and therefore, appropriate volume control in CAPD
      patients is especially important.

PMID- 9617496
TI  - Plasma and peritoneal endothelin levels and blood pressure in CAPD patients with
      or without erythropoietin replacement therapy.
AB  - The aim of the study was to determine the ET-1 concentration in peritoneal
      dialysate fluid and to investigate the relationship between peritoneal and plasma
      ET-1 levels and blood pressure in stable continuous ambulatory peritoneal
      dialysis (CAPD) patients with and without human recombinant erythropoietin (r
      HuEPO) replacement therapy. Twenty-seven stable CAPD patients were investigated.
      They completed their overnight exchange at the Dialysis Centre. Blood pressure
      was recorded and a blood sample was drawn. Biochemical parameters and ET-1 were
      measured in plasma and peritoneal dialysate fluid. Mean plasma ET-1 levels were
      increased by about four-fold in CAPD patients. ET-1 was detectable in peritoneal
      dialysate fluid and a significant correlation was observed between plasma and
      peritoneal ET-1 concentrations (r = 0.65, p < 0.01). The peritoneal clearance of
      ET-1 was lower than the creatinine clearance (1.69 +/- 0.08 ml/min vs. 3.96 +/-
      0.15 ml/min, p < 0.01). There was also a significant correlation between the time
      (months) on dialysis and plasma (r = 0.68, p < 0.01) or peritoneal dialysate ET-1
      levels (r = 0.46, p < 0.05). Mean blood pressure was higher in patients treated
      with r-HuEPO than in untreated patients (97 +/- 4 mmHg vs. 81 +/- 4 mmHg, p <
      0.01). Plasma and peritoneal dialysate ET-1 concentrations were comparable in the
      two groups with or without r-HuEPO replacement therapy and plasma ET-1 values
      correlated significantly with mean blood pressure only in r-HuEPO-treated
      patients (r = 0.63, p < 0.05 vs. r = 0.10, N.S. in untreated patients). In
      conclusion, plasma ET-1 concentrations are elevated in CAPD patients and the
      levels appear to increase with time on dialysis. ET-1 is cleared by the
      peritoneal membrane but at a much lower rate than creatinine. Blood pressure is
      higher in CAPD patients or r-HuEPO replacement therapy and blood pressure
      correlates with plasma ET-1 levels in these patients.

PMID- 9617497
TI  - Postpartum hemolytic uremic syndrome with a more severe liver involvement.
AB  - A 22-year-old woman presented with postpartum hemolytic uremic syndrome with a
      more severe hepatic involvement. The patient was dialysed and successfully
      treated with plasma infusion and intravenous immunoglobulin. Two months following
      discharge her creatinine clearance was 105 ml/min/1.73 m2, 99mTc DTPA scan and
      brain CT were normal. Here child is also alive and healthy.

PMID- 9617498
TI  - A case of immunotactoid glomerulopathy with unusual microtubular deposits.
AB  - A 57-year-old man with monoclonal gamma-globulinemia was admitted because of
      edema and proteinuria. A renal biopsy specimen showed lobular glomerulonephritis
      associated with deposition of material that was positive for IgG, C3, C1q,
      fibrin, kappa light chain, and lambda light chain but was not stained by Congo
      red. Glomeruli showed massive electron-dense deposits with two kinds of unusual,
      highly organized crystalline structures in the mesangial matrix and peripheral
      capillary loops. Clinically, the patient had nephrotic syndrome, microscopic
      hematuria, and hypertension. No Bence-Jones protein or cryoglobulin was found in
      the urine or serum. Immunoelectrophoresis of blood and urine revealed increased
      IgG-lambda paraprotein, but no free light chains were found. This case was not
      associated with amyloidosis, systemic lupus erythematosus, light chain deposition
      disease, cryoglobulinemia, or multiple myeloma. Immunotactoid glomerulopathy was
      diagnosed. Treatment with oral prednisone was effective for the management of
      nephrotic syndrome and renal dysfunction. Glomerular deposition of two kinds of
      microtubular structure in immunotactoid glomerulopathy has rarely been reported.

PMID- 9617499
TI  - Fibrillar crystal structure in essential monoclonal IgM kappa cryoglobulinemia.
AB  - In monoclonal IgG cryoglobulinemia, two types of crystallization have been
      demonstrated with electron microscopy at high magnification. In contrast, little
      information is available on well-defined crystallization in cases of monoclonal
      IgM cryoglobulinemia. We present a case of pure monoclonal IgM kappa
      cryoglobulinemia and rapidly progressive glomerulonephritis occurring in a 75
      year-old woman. We detected unequivocal formation of fibrillar crystal structure
      within intraglomerular macrophages on electron microscopy: the structure accords
      with that in a case of monoclonal IgG cyroglobulinemia described in the
      literature.

PMID- 9617501
TI  - Chronic pancreatitis associated with membranous glomerulonephritis.

PMID- 9617500
TI  - Castleman's disease with renal infiltration by polyclonal plasma cells.
AB  - A 52-year-old man was admitted to hospital because of declining renal function.
      Some months previously, biopsy from a mediastinal lymph node had shown
      Castleman's disease (angiofollicular lymph node hyperplasia). By now, a renal
      biopsy showed massive interstitial infiltration of predominantly plasma cells
      without significant atypia. On immunostaining, the plasma cells showed
      cytoplasmic reaction for IgG and kappa and lambda light chains, which had also
      been the case with the mediastinal lymph node. These findings were interpreted as
      interstitial renal involvement of Castleman's disease. The patient was treated
      with prednisone, upon which the renal function was stabilized, but not improved.
      The attention is drawn to Castleman's disease as a possible, although rare, cause
      of renal interstitial cellular infiltration.

PMID- 9617502
TI  - Compression of the inferior vena cava by right renal cysts: an unusual cause of
      IVC and/or iliofemoral thrombosis with pulmonary embolism in autosomal dominant
      polycystic kidney disease.

PMID- 9617503
TI  - Glomerular basement membrane antibodies in Hantavirus disease: any pathogenetic
      implication?

PMID- 9617504
TI  - Dialysis for a patient who had congenital deficiency of alpha 2-plasmin
      inhibitor.

PMID- 9617505
TI  - Pharmacology of pramipexole, a dopamine D3-preferring agonist useful in treating
      Parkinson's disease.
AB  - Pramipexole is a clinically effective nonergot dopamine agonist. Pramipexole's
      receptor interactions differ from ergot agonists in several ways. First, it has
      high selectivity for interacting with dopamine D2 subfamily receptors (D2, D3,
      and D4 receptor subtypes) and has little interaction with adrenergic or
      serotonergic receptors. Second, within the D2 subfamily, it has preferential
      affinity for the D3 receptor subtype, which, according to preclinical studies,
      could contribute additional efficacy for treatment of both motor and psychiatric
      syndromes in Parkinson's disease. Third, it has full intrinsic activity at
      dopamine D2 subfamily receptors. In addition to pramipexole's unusual receptor
      profile, whole-animal and cell culture studies suggest that pramipexole might
      provide neuroprotective effects through depression of dopamine metabolism,
      antioxidant effects, and stimulation of trophic activity. Pramipexole's
      demonstrated clinical efficacy for successful treatment in early disease for
      several years in the absence of L-dopa and as adjunctive therapy with L-dopa in
      late disease suggests a potential new paradigm for treatment of Parkinson's
      disease whereby new patients are initiated with pramipexole therapy and L-dopa is
      added only as necessary.

PMID- 9617506
TI  - Stepwise intravenous infusion of apomorphine to determine the therapeutic window
      in patients with Parkinson's disease.
AB  - A new experimental strategy was applied to determine the concentration-effect
      relation and the therapeutic window of apomorphine in individual patients with
      Parkinson's disease. Apomorphine was administered by a stepwise intravenous
      infusion. The infusion rate was increased by 10 micrograms/kg/h every 20 minutes,
      up to 100 micrograms/kg/h or less when adverse effects occurred. Thereafter, the
      infusion rate was decreased in a stepwise fashion until zero. Plasma apomorphine
      concentrations were measured every 20 minutes. Clinical efficacy (tapping score
      and tremor), dyskinesia, and adverse effects were monitored at the same time. The
      mean clearance of apomorphine was 4.5 L/min (2.2 to 6.6 L/min). Of the 10
      patients, 8 responded to apomorphine. The effects were quantal rather than
      continuous. Within each patient, the concentrations at onset and offset of effect
      generally were similar. Significant interpatient variability was observed with
      respect to minimal concentration for each of the effects. Clinical efficacy
      occurred at a mean minimal effective concentration (MEC) of 4.7 ng/mL (range 1.4
      to 10.7 ng/mL). Dyskinesia was observed at a mean concentration of 8.5 ng/mL
      (range 2.7 to 20 ng/mL). This value was not significantly different from the MEC.
      The mean minimal toxic concentration was 16.7 ng/mL (8.5 to 24.5 ng/mL) and was
      significantly different from the mean MEC. In conclusion, the stepwise increase
      and decrease of the intravenous infusion rate is a suitable tool for the
      establishment of the concentration-effect relation of apomorphine in individual
      patients. The finding of a narrow therapeutic window, in which the onset
      concentrations vary from patient to patient, underlines the need for accurate and
      individualized dosing.

PMID- 9617507
TI  - Pharmacokinetics, enantiomer interconversion, and metabolism of R-apomorphine in
      patients with idiopathic Parkinson's disease.
AB  - The pharmacokinetics and metabolism of R-apomorphine were determined in 10
      patients with idiopathic Parkinson's disease after intravenous infusion of 30
      micrograms.kg-1 in 15 min. Specifically, emphasis was on enantiomeric
      interconversion into S-apomorphine and on the formation of apocodeine and
      isoapocodeine, since these metabolites may interfere with the pharmacodynamics of
      R-apomorphine. The pharmacokinetics of R-apomorphine in plasma were determined
      using an enantioselective high-performance liquid chromatography assay. In most
      patients, the plasma concentration versus time profile was characterized by a
      biexponential function. The values of relevant pharmacokinetic parameters were as
      follows: clearance 40 +/- 15 ml.min-1.kg-1, volume of distribution at steady
      state 1.6 +/- 0.5 l.kg-1, and terminal half-life 41 +/- 13 min. No measurable
      concentrations of S-apomorphine were detected in plasma, indicating that
      enantiomeric interconversion does not occur in vivo. Furthermore, no measurable
      concentrations of the methylated metabolites apocodeine and isoapocodeine could
      be detected in plasma. The metabolism of apomorphine was characterized on basis
      of the excretion of unchanged R-apomorphine, S-apomorphine, apocodeine,
      isoapocodeine, and their respective sulfate and glucuronide conjugates in urine.
      The total excretion of unconjugated S-apomorphine, apocodeine, and isoapocodeine
      was less than 0.1% of the administered dose. The total excretion of unchanged
      apomorphine, apomorphine sulfate, and apomorphine glucuronide amounted to 0.3 +/-
      0.4%, 3.8 +/- 1% and 6.0 +/- 2.2% of the administered dose, respectively. The
      findings of this study show that on intravenous administration, S-apomorphine and
      the metabolites apocodeine and isoapocodeine are unlikely to interfere with the
      pharmacologic actions of R-apomorphine in patients with idiopathic Parkinson's
      disease. Furthermore, no pharmacokinetic interaction between R-apomorphine and
      catechol-O-methyl transferase inhibitors is expected.

PMID- 9617508
TI  - The safety of ropinirole, a selective nonergoline dopamine agonist, in patients
      with Parkinson's disease.
AB  - Ropinirole is a novel, nonergoline, selective D2-type dopamine agonist developed
      to treat Parkinson's disease. Safety data from therapeutic studies involving 1364
      patients receiving ropinirole are reported (mean daily dose 8.7 mg, early
      therapy; 8.2 mg adjunct therapy). In early therapy, the emergent adverse
      experiences more common with the ropinirole group compared with placebo were
      nausea, somnolence, leg edema, abdominal pain, vomiting, dyspepsia, and
      hallucinations. In adjunct therapy, they were dyskinesia, nausea, hallucinations,
      and confusion. Most adverse experiences were mild and associated with a similar
      withdrawal rate compared with the placebo group. Except for hallucinations, the
      incidence of emergent adverse experiences decreased with time, despite increasing
      doses. Long-term adverse experiences particularly associated with ergoline-type
      dopamine agonists have so far not been observed with ropinirole. Only 1.2% of
      patients receiving ropinirole developed dyskinesia compared with 11.2% receiving
      L-dopa in early therapy over a mean period of 17 months. There were no clinically
      significant changes in cardiovascular parameters or laboratory data. The
      incidence of adverse experiences in the bromocriptine group was low, possibly
      because of a slow titration scheme and low average dose. Overall, the safety
      profile of ropinirole appears similar to that of other dopamine agonists.
      Clinical studies are continuing to assess the long-term safety and efficacy of
      ropinirole.

PMID- 9617509
TI  - Risperidone compared with both lithium and haloperidol in mania: a double-blind
      randomized controlled trial.
AB  - Case reports and studies of other neuroleptics suggest the efficacy of
      risperidone in the treatment of mania. Forty-five inpatients with DSM-IV mania
      were studied in a 28-day randomized, controlled, double-blind trial of either 6
      mg daily of risperidone, 10 mg daily of haloperidol, or 800 to 1200 mg daily of
      lithium. The patients in all three groups showed a similar improvement on the
      total score for all rating scales at day 28 (Brief Psychiatric rating scale;
      lithium 9.1, haloperidol 4.9, risperidone 6.5, F = 1.01, df = 2, p = 0.37; Mania
      rating scale; lithium 15.7, haloperidol 10.2, risperidone 12.4, F = 1.07, df = 2,
      p = 0.35 [analysis of variance]). The Global Assessment of Functioning and
      Clinical Global Impression data showed a similar pattern of improvement. This
      study suggests that risperidone is of equivalent efficacy to lithium and
      haloperidol in the management of acute mania. The extrapyramidal side effects of
      risperidone and haloperidol were not significantly different.

PMID- 9617510
TI  - Biophysical membrane interactions of steroid hormones: a potential complementary
      mechanism of steroid action.
AB  - There is strong evidence to support the hypothesis that the rapid effects of
      steroids on neurons are membrane-mediated. Rapid steroid effects have been
      demonstrated in the absence of intracellular receptors, in the presence of RNA or
      protein synthesis inhibitors, and in response to steroids coupled to large
      proteins that block access to intracellular receptors. This study selectively
      reviewed the emerging body of evidence suggesting that steroids have multiple
      sites of cellular actions, and explored in depth one possible membrane-mediated
      mechanism of action, the membrane-intercalation model.

PMID- 9617511
TI  - Lisuride treatment of Alzheimer's disease. A preliminary placebo-controlled
      clinical trial of safety and therapeutic efficacy.
AB  - In this article, the authors examine the effect of lisuride on 22 patients with
      probable Alzheimer's disease (NINCDS/ADRDA criteria) in a randomized double
      blind, placebo-controlled, parallel group design. Ten patients received lisuride
      and 12 patients received placebo. Lisuride was administered in a dose-finding
      phase of four weeks and an efficacy phase of eight weeks, with a maximum dose of
      0.3 mg daily. Outcome measures included global clinical impression, general
      cognitive function, mood, verbal and visual memory, attention, and psychomotor
      function. Average decline in Mini-Mental State Examination score after 12 weeks
      treatment was less often statistically significant in lisuride treated patients
      than in patients receiving a placebo (p < 0.05). Patients treated with lisuride
      improved their average total score and short-delay cued recall score on the
      California Verbal Learning Test, a test of verbal memory, whereas placebo-treated
      patients showed worse performance compared with baseline. These differences
      approached statistical significance, with p = 0.06 and p = 0.05, respectively. No
      other differences between the treatment groups were evident. The authors failed
      to find a consistent effect of lisuride on symptoms of Alzheimer's disease.
      However, this study's sample size was relatively small, and larger studies are
      needed to ascertain the treatment effects of serotonergic antagonists on
      Alzheimer's disease.

PMID- 9617512
TI  - Botulinum toxin treatment for spasmodic dysphonia: percutaneous versus transoral
      approach.
AB  - Spasmodic dysphonia (SD) is at present defined as focal dystonia. Botulinum toxin
      (BT) injection is the treatment of choice for SD. BT is usually injected by a
      percutaneous route, but a direct, visually guided transoral approach has also
      been successful. It is not known whether percutaneous injection is as effective
      as the transoral approach. This article reviews our experience with both
      techniques of injection on 29 patients with adductor type SD. Since 1992, we have
      carried out 48 treatment sessions with the transoral technique and 76 treatment
      sessions with the percutaneous technique. Two patients did not respond to the
      percutaneous technique despite several attempts, but they did respond to the
      transoral approach. Globally, transoral technique was superior to percutaneous
      technique in terms of effectiveness (48 of 48 responses with transoral technique
      versus 61 of 76 responses with percutaneous approach, p < 0.01). Dosage of BT,
      duration, and side effects were similar with both techniques. This article also
      describes a simple, inexpensive device, composed of materials on hand at every
      hospital, that facilitates the transoral approach.

PMID- 9617513
TI  - Hemifacial spasm triggered by vasodilators.
AB  - Hemifacial spasm features myoclonic-like, paroxysmal, unilateral muscle
      twitching, attributable to vascular compression at the facial pontine root entry
      zone. We present the case of an 85-year-old man who presented with idiopathic
      hemifacial spasm with onset 23 years before. For the last 5 years, he was
      successfully treated with botulinum toxin injections. However, occasional nitrate
      intake for precordial pain promptly triggered muscle twitching. Vasodilation may
      exacerbate not only cases of hemifacial spasm, but even of trigeminal neuralgia,
      both recognized as neurovascular compressive syndromes.

PMID- 9617514
TI  - Alprazolam withdrawal delirium: a case report.
AB  - Benzodiazepine withdrawal delirium is thought to be uncommon. Only two clear
      reports of alprazolam withdrawal appear in the literature, but the use of this
      drug is expected to increase because of its recent approval for the treatment of
      panic disorder. We report on a patient with severe alprazolam withdrawal delirium
      that developed immediately after an accidental reduction of the dose. This case
      demonstrates importance of clinician awareness of the previous use of alprazolam
      in individual patients, especially in hospital settings where free patient use of
      drugs is prohibited.

PMID- 9617515
TI  - Clozapine and pancreatitis.

PMID- 9617516
TI  - Adaptive smoothing of MR brain images by 3D geometry-driven diffusion.
AB  - The paper deals with the iterative three-dimensional (3D) smoothing of tomograms
      acquired by fast Magnetic Resonance (MR) imaging methods. The smoothing method
      explored, which is aimed basically at the improvement of 3D visualization
      quality, uses the physical concept of geometry-driven diffusion with a variable
      conductance function, based on a specific measure of the 3D neighborhood
      homogeneity. A novel stopping criterion is proposed for iterative 3D diffusion
      processing. A study of the transition from 2D to 3D algorithms is carried out.
      The main structure of the program implementation of the smoothing algorithms
      developed is described. Three smoothing/filtering methods, aimed at the
      improvement of 3D visualization of MR tomograms of the brain, are quantitatively
      and visually compared using real 3D MR images. The results of computer
      simulations with 3D smoothing, segmentation and visualization are presented and
      discussed.

PMID- 9617517
TI  - A study of medical emergency workflow.
AB  - In this paper, the authors introduce a workflow model. The development of
      computer network technology enables us to share the distributed data in real
      time. It is a considerable significance in the practical application of network
      capabilities not only to office work but also to the medical environment. In
      order to construct a well-connected, managed post (environment, scene), a model
      is needed to design the workflow. Here we propose a workflow model to cope with
      the scene of unforeseen events that we usually encounter in daily clinical
      activities. We give careful consideration to the ability of this model to manage
      dynamic changes within the workflow and describe its application to a medical
      scene (triage) and then carry out simulations based on this model. The authors
      are able to demonstrate the validity of this model through this simulation.

PMID- 9617518
TI  - A rapid matching algorithm for cerebral 3D images using 1D projection.
AB  - A rapid image matching algorithm for cerebral three-dimensional (3D) images is
      described. Fully automatic 3D image matching between images acquired the same
      modality and this was realized by applying the following sequential processes:
      (1) the calculation of one-dimensional (1D) projection patterns from both
      reference and input 3D images; (2) the matching between the two sets of 1D
      patterns; and (3) the transformation of input 3D image according to the pattern
      matching result. The 3D morphological variations among images due to shift and
      linear/non-linear scaling along projection axes were recovered, as well as
      compensation for mismatching due to image rotation and partial deficit of image
      data. The computation time of this method was quite short compared to that of the
      conventional 3D pattern matching method.

PMID- 9617519
TI  - WinArrhythmia: a Windows based application for studying cardiac arrhythmias.
AB  - We have developed Windows-based software for ECG training as a tool in teaching
      physiology. A standard user interface allows the user to choose which arrhythmia
      to review. The arrhythmia is drawn in real time with sound beeps synchronized to
      R waves. The system also presents a brief summary or multiple choice question
      corresponding to the arrhythmia. A ladder diagram shows how simulate the
      conduction system, which consisted of 4 modules characterized by 4 parameters:
      automaticity, refractory period, antegrade- and retrograde-conduction time. This
      system has proved both useful and effective for training medical students in ECG
      interpretation of arrhythmias.

PMID- 9617520
TI  - NLMEM: a new SAS/IML macro for hierarchical nonlinear models.
AB  - Analysis of longitudinal data is one of the most challenging tasks in statistical
      modeling. In the analysis, it is often necessary to take into account nonlinear
      response to a set of parameters of interest and correlation between measurements
      taken from the same individual. In addition, between- and within-subject
      variation has to be handled properly. An example of addressing these issues is
      the hierarchical nonlinear model, where parameter estimation can be performed
      using linearization method. In this paper a new NLMEM SAS/IML macro for
      hierarchical nonlinear models is proposed. The program uses a portion of the code
      developed earlier in NLINMIX. NLMEM retains all the benefits of NLINMIX while
      allowing the systematic part of the model structure to be specified using IML
      syntax. Consequently, NLMEM allows estimation of models which are not tractable
      using NLINMIX. In particular, it allows us to address advanced population
      pharmacokinetics and pharmacodynamics models specified by ordinary differential
      equations.

PMID- 9617521
TI  - A genetic-based machine learning system to discover the diagnostic rules for
      female urinary incontinence.
AB  - A machine learning system named Galactica has been developed which uses a genetic
      algorithm to discover the rules for an expert system from databases. Galactica
      devised accurate diagnostic rules for female urinary incontinence from difficult
      heterogeneous data. The percentages of correctly classified stress, mixed and
      sensory urge incontinence testing cases were 89, 86 and 87%, respectively.
      However, these rules were rather general, consisting of 4-6 out of 13 conditions
      available in the data. Diagnostic rules for stress and mixed incontinence
      extracted from straightforward homogeneous data were highly accurate, classifying
      100% of testing cases correctly as well as being specific, having from 10 to 11
      conditions. More specific, but less accurate, rules were found from heterogeneous
      data with a biased fitness function. All of the rules were correct, i.e. every
      condition in the rules had the expected value specified by the expert. Although,
      Galactica achieved a slightly better classification than the discriminant
      analysis, it is argued that the genetic approach is better than the statistical
      one, due to symbolic rules being comprehensible, whereas understanding a complex
      mathematical model requires statistical expertise.

PMID- 9617522
TI  - The application of wavelets to retinal image compression and its effect on
      automatic microaneurysm analysis.

PMID- 9617523
TI  - Stochastic complexity as a taxonomic tool.
AB  - In this paper we propose a method of constructing a hierarchical classification
      based on the notion of stochastic complexity. Minimization of stochastic
      complexity amounts to maximization of the information content of the
      classification. A dendrogram is obtained by first finding the classification
      which minimizes stochastic complexity and then by step-wise merging of groups
      such that at each step there is a minimum loss of information. The method was
      applied to a database containing 5313 strains of Enterobacteriaceae. The results
      are in reasonable accordance with present-day views on the taxonomy of
      Enterobacteriaceae.

PMID- 9617524
TI  - Computer-generated time lines for visualizing and editing epidemiological and
      biomedical data.
AB  - Most biomedical data have a temporal dimension. Time-line displays spatialize
      this dimension and help the viewer comprehend large sets of complex data. If we
      add ways for users to selectively expand the details of data visible on a time
      line, even more information can be organized and accessed. Design issues for this
      kind of display include: how to display time scales that are often wider than the
      physical display space; how to display events with brief duration; how to display
      data for two or more events that overlap in time; how to manage the display of
      data details; how to allow database editing from a time line; and how to
      facilitate time-based analytical techniques. We describe a time-line display
      system that addresses each of these issues, and show how it can be used to
      organize data for an epidemiological study of parental radiation exposure and
      childhood leukemia. We also suggest further refinements of the time line
      technique for other biomedical applications.

PMID- 9617525
TI  - An Internet-based ontology editor for medical appropriateness criteria.
AB  - Appropriateness criteria and practice guidelines seek to promote the cost
      effectiveness use of medical interventions, and can be most useful when
      integrated with computer-based patient records and order-entry systems. Building
      an abstract model (ontology) of appropriateness criteria can require considerable
      effort among investigators at geographically dispersed institutions. To
      facilitate the construction and maintenance of ontologies for clinical
      appropriateness criteria, the author developed an Internet-based system for
      viewing and editing the knowledge model. The system, called NEON (Network-based
      Editor for ONtologies), uses the World Wide Web as a platform-independent user
      interface. NEON allows users to edit the indexing terms and the semantic network
      that form the ontology for a set of appropriateness criteria. Ontologies built
      using the system can be imported and exported using an open, internationally
      standardized format based on the Standard Generalized Markup Language (SGML).

PMID- 9617526
TI  - POLYAN: a computer program for polyparametric analysis of cardio-respiratory
      variability signals.
AB  - A polyparametric approach to the study of cardiovascular and respiratory systems,
      with the analysis of several simultaneously recorded signals and of their mutual
      relationships, is essential for the assessment of autonomic regulation. A
      computer program which implements all the procedures used in this investigative
      context and also makes the approach easy for researchers without an engineering
      background is described. Spectral techniques (univariate and bivariate), time
      domain techniques and non invasive baroreflex sensitivity assessment are
      available and integrated in the same package. In order to allow the flexibility
      and easy expandability required in a research tool, POLYAN was written in Matlab.
      POLYAN is currently used in our Hospital by several research groups and is a
      fundamental research tool for the interdisciplinary assessment of the autonomic
      nervous system. Establishing a common analysis framework, POLYAN has made sharing
      new findings and co-operating in research work much easier.

PMID- 9617527
TI  - STEREO: a program on a PC-Windows 95 platform for recording and evaluating
      quantitative stereologic investigations of multistage hepatocarcinogenesis in
      rodents.
AB  - The most common organ site of neoplasms induced by carcinogenic chemicals in the
      rodent bioassay is the liver. The development of cancer in rodent liver is a
      multistage process involving sequentially the stages of initiation, promotion,
      and progression. During the stages of promotion and progression, numerous lesions
      termed altered hepatic foci (AHF) develop. STEREO was developed for the purpose
      of efficient and accurate quantitation of AHF and related lesions in experimental
      and test rodents. The system utilized is equipped with a microcomputer (IBM
      compatible PC running Windows 95) and a Summagraphics MICROGRID or SummaSketch
      tablet digitizer. The program records information from digitization of single or
      serial sections obtained randomly from rat liver tissue. With this information
      and the methods of quantitative stereology, both the number and volume percentage
      fraction of AHF in liver are calculated in three dimensions. The recorded data
      files can be printed graphically or in the format of tabular numerical data. The
      results of stereologic calculations are stored on floppy disks and can be sorted
      into different categories and analyzed or displayed with the use of statistics
      and graphic functions built into the overall program. Results may also be
      exported into Microsoft Excel for use at a later time. Any IBM-compatible PC
      capable of utilizing Windows 95 and MS Office can be used with STEREO, which
      offers inexpensive, easily operated software to obtain three-dimensional
      information from sections of two dimensions for the identification and relative
      potency of initiators, promoters, and progressors, and for the establishment of
      information potentially useful in developing estimations of risk for human
      cancer.

PMID- 9617528
TI  - VR interaction techniques for medical imaging applications.
AB  - Methods of virtual reality (VR) offer new ways of human-computer interaction.
      Medicine is predestined to benefit from this new technology in many ways. Virtual
      environments can support physicians in their work, alleviate communication
      between specialists from different fields or be established in educational and
      training applications. For the field of visualization and analysis of three
      dimensional anatomical images (e.g. CT or MRI scans), an application is
      introduced which expedites recognition of spatial coherencies and the exploration
      and manipulation of the 3D data. To avoid long periods of learning and
      accustoming and to facilitate work in such an environment, a powerful human
      oriented interface is required allowing interactions similar to the real world
      and utilization of our natural experiences. This paper shows the use of eye
      tracking parameters for a level-of-detail algorithm and the integration of a
      glove-based hand gesture recognition into the virtual environment as an essential
      component of the human-machine interface. Furthermore, virtual bronchoscopy and
      virtual angioscopy are presented as examples for the use of the virtual
      environment.

PMID- 9617529
TI  - Cardiovascular safety and combined oral contraceptives.

PMID- 9617530
TI  - The collection and interpretation of epidemiological data about the
      cardiovascular risks associated with the use of steroid contraceptives.
AB  - A variety of epidemiological approaches have been used to assess the safety of
      steroid contraceptives. Each study design has its own strengths and weaknesses,
      especially with respect to susceptibility to bias and confounding. Randomized
      controlled trials provide the strongest evidence of a cause and effect
      relationship, but the low incidence of cardiovascular disease in women of
      reproductive age precludes the use of this study design to examine these clinical
      endpoints. Consequently, observational cohort and case-control studies have
      provided the most useful clinical information about the main cardiovascular
      effects of steroid contraceptives. Data from epidemiological research need to be
      interpreted carefully taking into consideration which of the potential biases or
      sources of confounding are likely to have affected a particular study, and what
      effect these may have on any inferences from the study. Additional factors that
      need to be considered before deciding whether a causal relationship exists
      include evidence that the exposure preceded the disease, the strength of
      association, consistency of findings with other studies, presence of dose
      gradients, and agreement with animal or laboratory research. Even if a casual
      link is thought to be plausible, the public health implications may be minimal;
      absolute (attributable) risks are required in order to assess these. An
      understanding of these epidemiological issues will enable clinicians to advise
      their clients whether steroid contraceptives alter the risk of cardiovascular
      disease and, if so, the clinical significance of such changes.

PMID- 9617531
TI  - Oral contraceptive use and myocardial infarction.
AB  - Epidemiologic studies of current oral contraceptive (OC) use and myocardial
      infarction (MI) have been contradictory and confusing. This comprehensive review
      of the epidemiologic literature attempts to draw conclusions about the risk of
      myocardial infarction in oral contraceptive users, focusing on recent,
      methodologically rigorous studies of the topic. Recent studies are consistent in
      showing a higher relative risk of MI in current OC users who smoke compared with
      current OC users who do not smoke. Studies in aggregate suggest that the relative
      risk of MI is higher in current OC users with hypertension than in current OC
      users without hypertension. Recent studies do not show a relationship between
      higher estrogen dose and higher risk of MI, but the effect of estrogen dose and
      progestogen type and dose are difficult to separate. The limited data on the risk
      of MI in current users of low estrogen OC do not allow a firm conclusion about
      the possibility that progestogen type might affect the risk of MI in current
      users. Past OC use does not increase or decrease the risk of MI.

PMID- 9617532
TI  - Stroke and steroid hormonal contraception.
AB  - The rate of stroke in young women has been falling for some years. The data
      presented here suggest that the relative risk associated with oral contraceptive
      use also is falling. This is probably due to a combination of younger age at use
      of oral contraceptives, lower steroid dose of preparations, and more systematic
      screening of potential users; particularly with respect to blood pressure. The
      risk associated with oral contraceptive use is greater for occlusive stroke but
      increases with age in hemorrhagic stroke. Risk of occlusive stroke increases with
      increasing doses of estrogen. The evidence for a risk related to type or dose of
      progestogen is less consistent, but there is no support for an increase in risk
      associated with use of desogestrel or gestodene.

PMID- 9617533
TI  - Newer oral contraceptives and the risk of venous thromboembolism.
AB  - Research on the relationship between venous thromboembolism and the progestagen
      content of combined oral contraceptives has pointed to an increase in risk
      associated with products containing desogestrel and gestodene. Although many
      biases must have been at play in these nonexperimental studies, the errors that
      have been suggested and examined are not of a sufficient magnitude to account for
      the observed results. The most plausible explanation of the available data is
      that combined oral contraceptives containing desogestrel and gestodene carry a
      very small risk of venous thromboembolism, which exceeds the even smaller risk
      carried by products containing levonorgestrel. The position of norgestimate is
      uncertain.

PMID- 9617534
TI  - Metabolic interrelationships, cardiovascular disease, and sex steroids.
AB  - Future studies of the pharmacodynamics of oral contraceptives should encompass
      interactions between various areas of physiology rather than concentrate on
      single metabolic processes. Changes in one area of metabolism may affect other
      areas. Insulin plays a central role in metabolic control and, in addition to
      profound effects on carbohydrate and lipid metabolism, also affects the
      hematological system. Insulin has been proposed as a major physiological
      regulator of plasminogen activator inhibitor, and hyperinsulinemia is associated
      with increased blood coagulability and decreased fibrinoloysis. There is a close
      relationship between insulin and triglyceride metabolism, and this may affect
      factor VII activity in blood. There are many interactions between lipid
      metabolism and hematological factors. The apoprotein of lipoprotein (a) is
      structurally similar to plasminogen. Tissue factor pathway inhibitor, a regulator
      of coagulation, circulates in blood bound to LDL and HDL. Some fatty acids may
      act as a contact surface for activation of hematological factors. Dietary factors
      also need to be considered. Changes not only in the quantity but also in the
      composition of dietary fat influence lipid metabolism and also blood levels of a
      number of hematological factors. Other aspects of pharmacodynamic studies that
      require consideration and other factors that affect metabolic interrelationships
      are discussed.

PMID- 9617536
TI  - Blood coagulation and oral contraceptives. A critical review.
AB  - The use of oral contraceptives is associated with altered plasma concentrations
      of many components of the coagulation and fibrinolysis system, increased plasma
      levels of markers indicating in vivo coagulation and fibrinolysis, and a modified
      response to challenge tests both in vivo and in vitro. None of these effects
      seems to be specific for users of oral contraceptives and none was found
      uniformly in all users. The predictive value of each of these effects, or even of
      certain combinations of tests, for the prediction of venous thrombosis is low.
      There is no established way to assess the "thrombogenicity" of particular pills.
      The individual susceptibility, however, to develop venous thrombosis varies
      considerably. Recently, several congenital abnormalities of the hemostatic system
      have been found that are associated with an increased risk of venous thrombosis
      in general. The risk associated with the use of oral contraceptives appears to
      act synergistically with some of these thrombophilic conditions. Although the
      prevalence of these congenital predispositions varies among different
      populations, screening for these conditions is not feasible: negative results
      would not exclude the occurrence of about two-thirds of oral contraceptives
      associated thromboses and positive results are likely to be disregarded because
      of their poor predictive value. Future research has to evaluate the role of a
      more targeted screening strategy aiming at women with risk factors such as a
      positive personal or family history of venous thromboembolism.

PMID- 9617535
TI  - Safety evaluation of modern oral contraceptives. Effects on lipoprotein and
      carbohydrate metabolism.
AB  - An ideal oral contraceptive should either be neutral as regards metabolic risk
      markers for arterial disease or should only change them in directions that would
      be expected to reduce risk. Depending on their formulation, modern low dose oral
      contraceptives affect systems such as hemostasis, lipoprotein metabolism, and
      glucose and insulin metabolism. Some of these actions would be expected to
      decrease the risk of arterial disease and some might be expected to increase
      risk. Despite these associations there is at present no justification for
      widespread metabolic screening as a strategy to further improve oral
      contraceptive safety. Recent developments in atherosclerosis research support the
      introduction of progestogens such as desogestrel that allow the estrogenic
      increase in high density lipoprotein levels to persist and that may cause less of
      an elevation in plasma insulin responses to glucose. The predicted benefit of
      these formulations in terms of arterial disease is difficult to demonstrate in an
      epidemiological setting because of the rarity of the disease in young women.

PMID- 9617537
TI  - Hormonal contraception and risk of cardiovascular disease. An international
      perspective.
AB  - The most frequent major adverse effect of hormonal contraception is an increased
      risk of cardiovascular disease. The effect on the risk of venous thromboembolism
      (VTE), ischemic and hemorrhagic stroke, and myocardial infarction (MI) differs
      and is strongly influenced by smoking and the presence of other cardiovascular
      risks factors, such as hypertension and diabetes mellitus. The incidence of each
      disease rises with age and there are differences in risk among hormonal
      contraceptive preparations. This article provides a framework within which to
      assess the balance of risks among types of hormonal contraceptives according to
      individual circumstances. Data on cardiovascular disease mortality rates in women
      of reproductive age in different countries of the world were compiled from
      nationally reported statistics and supplemented where possible with reported
      disease incidence rates. Risks associated with current use of hormonal
      contraception were compiled from the most recent publications on the
      cardiovascular effects of steroid hormone contraception. These were combined to
      estimate the total cardiovascular incidence and mortality according to baseline
      cardiovascular risk and individual characteristics. Mortality rates for
      cardiovascular diseases are very low in women of reproductive age. Myocardial
      infarction mortality rates rise from < 0.4 per 100,000 woman-years at age 15-24
      years to the range 2 to 7 per 100,000 woman-years at age 35-44 years. Stroke
      mortality rates similarly rise steeply with age and are between 3 and 5 times
      higher than those for MI. VTE mortality rates rise less steeply with age and are
      approximately one-tenth the MI mortality rates at age 35-44 years. The adverse
      effect of oral contraceptives (OC) on the risk of VTE is the most important
      contributor to the total number of cardiovascular cases attributable to OC use.
      The increased risk of stroke and MI dominate the patterns of mortality in OC
      users and smokers. The additional risks attributable to smoking are greater than
      the additional risks attributable to OC use. The risk attributable to OC use in
      women < 35 years of age is small, even if they smoke, but there are substantially
      increased risks in older women who both smoke and use OC. The additional
      mortality attributable to OC use can be reduced by screening users, as this
      results in lower relative risks of ischemic stroke and MI. Differences between OC
      types in the relative risk of VTE contribute little to the total cardiovascular
      mortality associated with OC use, even though the total number of cardiovascular
      events is increased. A potential reduction in the risk of MI with desogestrel and
      gestodene compared with levonorgestrel-containing OC would have little difference
      on overall mortality rates in women in their 20s and 30s, but may result in a net
      reduction in OC-attributable mortality in women aged 40-44 years who smoke. An
      overall quantification of the risks for different types of oral contraceptive
      users is necessary for an informed choice of contraceptive method, and any
      assessment of the balance of cardiovascular risks is complex. The model provides
      a tool to assess, at the level of the individual, the risks associated with use
      of different OC according to personal circumstances. It is important to consider
      the user's age and smoking status when determining OC attributable risks.

PMID- 9617538
TI  - Scanning laser ophthalmoscopy of the optic disc at the level of the lamina
      cribrosa.
AB  - PURPOSE: To determine the suitability and reproducibility of optic disc
      morphometry performed on images focused at the level of the lamina cribrosa,
      obtained by means of the scanning laser ophthalmoscope (SLO). METHODS: Twenty-one
      eyes were imaged with argon blue and green, helium neon red and diode infrared
      laser sources of a scanning laser ophthalmoscope. Five images of the optic disc
      at the level of the lamina cribrosa were taken for each patient, digitized and
      traced by three trained observers, in order to identify the external contour of
      the optic disc and the inner edge of the neuroretinal rim. Dedicated software
      allowed the contours to be traced on the video and an estimate of the real sizes
      of optic disc parameters to be obtained according to Littman's equation. Standard
      deviation (SD) and coefficient of variation (CV) were used to determine the intra
      and inter-observer reproducibility in measuring disc, dark annulus (DA), and
      reflective center (RC) areas, DA area/disc area (DA/D) and RC area/disc area
      (RC/D) ratios of each set of images taken with all laser wavelengths. RESULTS: A
      high contrast between the dark annulus of the lamina and the central highly
      reflective area was achieved at all laser wavelengths. The ranges of CVs for all
      of the observers, using all the laser wavelengths, were as follows: disc: 0.018
      0.036; dark annulus: 0.015-0.039; reflective center: 0.014-0.031; DA/D: 0.005
      0.01; RC/D: 0.007-0.018. No significant difference was observed between the
      measurements performed on the images acquired, using the different laser
      wavelengths. CONCLUSIONS: SLO imaging of the optic disc at the level of the
      lamina cribrosa proved to be suitable and highly reproducible at all laser
      wavelengths. The coefficients of variation of the measurements of optic disc
      parameters obtained using this technique are smaller than those obtained by means
      of conventional photographic methods.

PMID- 9617539
TI  - Expression of nuclear retinoic acid receptor and retinoid X receptor mRNA in the
      cornea and conjunctiva.
AB  - PURPOSE: The effects of retinoic acid in cells are mediated by the nuclear
      retinoic acid receptors (RARs) and retinoid X receptors (RXRs). Although vitamin
      A is essential for the normal development and maintenance of the ocular surface,
      the RARs and RXRs have not been studied in cornea and conjunctiva. The purpose of
      this study was to identify the mRNA for these receptors in corneal and
      conjunctival cells in culture and to determine whether all-trans retinoic acid is
      able to induce expression of RAR mRNA. METHODS: Total RNA was extracted from
      cultured rabbit corneal stroma and conjunctival fibroblasts and rabbit corneal
      epithelial cells. RNA was analyzed by Northern blotting using the cDNA probes for
      RAR alpha, RAR beta, RAR gamma, RXR alpha, RXR beta and RXR gamma mRNA. To
      investigate induction of retinoid receptors, cells were exposed to 10(-6) M all
      trans retinoic acid for 2-48 h before preparation of RNA. Effects of retinoic
      acid on cell proliferation were also investigated. RESULTS: RAR alpha mRNA
      transcripts (3.7 kb), RAR beta mRNA transcripts (3.3 kb) and RAR gamma mRNA
      transcripts (3.3 kb) are expressed by all the cell types studied, as are the RXR
      alpha mRNA transcripts (5.0 kb) and RXR beta mRNA transcripts (3.3 kb). RXR gamma
      mRNA is not detectable in corneal and conjunctival cells. All-trans retinoic acid
      induced RAR beta mRNA expression in corneal and conjunctival fibroblasts.
      Increased mRNA levels were detectable after 4-8 h and peaked by 24 h. RAR beta
      mRNA was not induced by retinoic acid in corneal epithelial cells. Retinoic acid
      also inhibited proliferation of conjunctival and corneal fibroblasts but had no
      effect on growth of corneal epithelial cells. CONCLUSIONS: The expression of RARs
      and RXRs in the cornea and conjunctiva is similar to that reported in other
      tissues. The identification of these receptors may lead to a better understanding
      of gene transcription pathways in the cornea and conjunctiva and of the
      mechanisms that control keratinization, differentiation and proliferation of the
      cells of these tissues. The data suggest a relationship between the induction of
      RAR beta mRNA expression and inhibition of cell proliferation by retinoic acid.

PMID- 9617540
TI  - Thermal and mechanical stability of the lens capsule.
AB  - PURPOSE: Several procedures in cataract surgery carry the risk of high
      temperature increases in the capsular bag. The present study was undertaken to
      determine the shrinkage temperature of the human lens capsule and to investigate
      the effect of temperature on the mechanical behavior of the lens capsule. METHOD:
      Thermal-shrinkage characteristics of the lens capsule were determined during
      gradual heating of circular specimens (2 mm in diameter) prepared from anterior
      lens capsules from 25 human donors, ranging in age from 20 to 98 years. Uniaxial
      mechanical testing was carried out at 22 degrees C, 36 degrees C and 61 degrees C
      on ring-shaped test specimens prepared from anterior lens capsules from 5- to 6
      month-old pigs. RESULTS: The mean shrinkage temperature (Ts) for the human lens
      capsule was 51.5 degrees C (range 49.3-54.3) and the mean shrinkage area in
      percent of the original area (AST) was 49% (36-66). Ts was significantly
      associated with the age of the donors and decreased 0.1 degree C per year until
      age 65 after which Ts was found to increase. AST showed no association with age.
      The mechanical effect of temperatures below the shrinkage temperature was modest.
      The capsule became slightly more extensible with increasing temperature. The
      effect of temperatures above the shrinkage temperature was an increased ultimate
      strain, a reduced ultimate stiffness and a slightly reduced ultimate stress.
      CONCLUSION: Thermal stability of the human lens capsule (type IV collagen) seems
      to be considerably lower than that of fibrous connective tissue (type I
      collagen). A potential risk of capsular shrinking has to be taken into account
      when the capsule is exposed to thermal stress during cataract surgery.

PMID- 9617541
TI  - Comparison of topical antibiotics for treating Mycobacterium chelonae keratitis
      in a rabbit model.
AB  - PURPOSE: To investigate the effect of topical amikacin (25 mg/ml), imipenem (25
      mg/ml), ciprofloxacin (3 mg/ml), clarithromycin (20 mg/ml), amikacin combined
      with ciprofloxacin, amikacin combined with imipenem, and amikacin combined with
      clarithromycin on Mycobacterium chelonae keratitis. METHODS: Ninety New Zealand
      albino rabbits were infected with a strain of M. chelonae for which minimum
      inhibitory concentration indicated in vitro sensitivity to the above antibiotics.
      The rabbits were treated for one or two weeks. The treatment efficacy was judged
      by the size of stromal infiltrate and quantitative culture of the infected
      corneas. RESULTS: The size of the stromal infiltrate showed no significant
      difference in treated eyes compared to the untreated, control eyes. However, all
      treatments significantly reduced the number of organisms in treated eyes compared
      to untreated, control eyes (all p-values < 0.05). No significant difference in
      treatment efficacy was found between individual treatment groups. In none of the
      cases were organisms eliminated from the infected eyes, even after 2 weeks of
      treatment. CONCLUSIONS: The results suggest that topical amikacin, imipenem,
      ciprofloxacin and clarithromycin had some therapeutic effect on M. chelonae
      keratitis; however, amikacin combined with imipenem, ciprofloxacin, and
      clarithromycin showed no increased efficacy over single agent therapy during 2
      weeks of treatment. Long term treatment may be required to eradicate M. chelonae.

PMID- 9617542
TI  - Effects of retinoic acid and TGF-beta 1 on the proliferation and melanin
      synthesis in chick retinal pigment epithelial cells in vitro.
AB  - PURPOSE: The purpose of this study was to investigate the effects of all-trans
      retinoic acid (RA) and transforming growth factor-beta 1 (TGF-beta 1) on
      proliferation and melanin synthesis of chick retinal pigment epithelial (RPE)
      cells in vitro. METHODS: Chick RPE cells were cultured in the presence or absence
      of RA (10(-5) to 10(-7) M) or TGF-beta 1 (1 to 100 U/ml) for a 10-day period. The
      effects of RA and TGF-beta 1 on RPE cell proliferation were assessed by counting
      the number of cells, and their effects on melanin synthesis were evaluated by
      measuring the melanin content in the cells. RESULTS: RA significantly inhibited
      RPE cell proliferation in a time-dependent manner. The most marked inhibition was
      observed on day 10 of culture, and the most effective concentration of RA was 10(
      6) M. Melanin synthesis was increased on day 10, and the most effective
      concentration of RA was also 10(-6) M. TGF-beta 1 also inhibited RPE cell
      proliferation and increased melanin synthesis. CONCLUSIONS: These findings
      indicate that RA and TGF-beta 1 have regulatory effects on the proliferation and
      differentiation of chick RPE cells in vitro.

PMID- 9617543
TI  - Hyperoxia stimulates endothelin-1 secretion from endothelial cells; modulation by
      captopril and nifedipine.
AB  - PURPOSE: Retinopathy of prematurity (ROP) is a vasoproliferative condition that
      can result in severe visual impairment and blindness in preterm babies. Two
      conditions seen very early in radioimmunoassay (ROP) are vasoconstriction and
      vaso-obliteration. A potent vasoconstrictor secreted by endothelial cells is
      endothelin-1 (ET-1). Premature birth results in a relative systemic hyperoxia,
      compared to the in utero oxygen milieu. We tested the hypothesis that hyperoxia
      increases ET-1 expression as a possible mechanism for vasoconstriction in the
      retinal vasculature. METHODS: Bovine retinal endothelial cells and adrenal
      capillary endothelial cells were isolated and maintained in culture. Cells were
      exposed to control or hyperoxic culture conditions for 24 h, with and without
      addition of captopril and nifedipine. Media was collected and assayed for ET-1 by
      ROP. In addition, cell counts and secreted LDH assays were performed. RESULTS:
      Conditioned media from cultured bovine retinal and adrenal endothelial cells
      exposed to hyperoxic culture conditions for 24 h were found to have higher levels
      of ET-1 than conditioned media from normoxic control cells. Captopril (10(-6) M
      and 10(-4) M) and nifedipine (10(-6) M and 10(-4) M) inhibited ET-1 release from
      hyperoxia-exposed endothelial cells. Under normoxic conditions, ET-1 release was
      inhibited by 10(-4) M captopril or 10(-4) M nifedipine. CONCLUSIONS: These
      results demonstrate that (1) hyperoxia stimulates in vitro ET-1 secretion in
      bovine retinal and adrenal capillary endothelial cells, and (2) captopril and
      nifedipine downregulate ET-1 secretion under normoxic and hyperoxic culture
      conditions, in a dose-dependent fashion. We speculate that ET-1 may be involved
      in retinal vessel vasoconstriction seen early in the development of ROP. Further,
      ACE inhibitors and calcium-channel blocking agents, such as captopril and
      nifedipine, may provide an avenue for blocking vasoconstriction in ROP.

PMID- 9617544
TI  - Continuous exposure to bright light upregulates bFGF and CNTF expression in the
      rat retina.
AB  - PURPOSE: To examine mRNA expression of neurotrophic factors in the retina after
      exposure to bright light. METHODS: Male adult Sprague-Dawley rats were exposed to
      light of 115-130 ft-c. Retinas were collected after 1, 2, 4 or 7 days of
      exposure. Northern blot analysis was performed to determine mRNA levels for the
      following factors and their receptors: basic fibroblast growth factor (bFGF),
      ciliary neurotrophic factor (CNTF), acidic fibroblast growth factor (aFGF), brain
      derived neurotrophic factor (BDNF), insulin-like growth factor 1 (IGF-1) and
      glial fibrillary acidic protein (GFAP). Expression of bFGF, CNTF and GFAP was
      localized by in situ hybridization. RESULTS: Exposure to light of 115-130 ft-c
      resulted in a substantial increase in bFGF and CNTF expression that persisted
      during the entire 7-day period of exposure. The peak expression of bFGF was
      almost 9-fold at day 2. The increase in CNTF mRNA reached a maximum of 6-fold at
      day 4. A small increase (50%) in IGF-1 mRNA was also seen at day 4. Among the
      receptors, an elevation of 3-fold in FGF receptor 1 (FGFR-1) was observed at day
      2. There was also a small increase (70%) in IGF-1 receptor (IGF-1R) at day 2. In
      addition, the expression of GFAP showed a rapid elevation of about 8-fold by day
      1 and 9-fold by day 2, and 18-fold by day 4. There was, however, no significant
      alteration in the expression of aFGF and BDNF. In situ hybridizations showed that
      the elevation of bFGF, CNTF and GFAP occurred across the entire retina with
      especially prominent increases over specific layers for each gene. CONCLUSIONS:
      Continuous exposure to bright light upregulates bFGF, CNTF, FGFR-1 and GFAP
      expression in the rat retina. The pattern of induced expression closely resembles
      that induced by mechanical injury, implying a common underlying mechanism.

PMID- 9617545
TI  - The role of platelet-activating factor in cell infiltration in endotoxin-induced
      uveitis in guinea pigs.
AB  - PURPOSE: We investigated the role of platelet-activating factor (PAF) in cell
      infiltration in endotoxin-induced uveitis (EIU) in guinea pigs. METHODS: To
      elicit EIU, lipopolysaccharide (LPS) was injected into the anterior chamber of
      the eye. Cell numbers in the aqueous humor after LPS injection were determined by
      flow cytometry. PAF and prostaglandin E2 (PGE2) production after LPS injection
      were also examined. RESULTS: Intracameral injection of LPS induced cell
      infiltration into the anterior chamber, and platelet-activating factor (PAF) was
      detected in the aqueous humor. In addition, topical apafant (PAF antagonist)
      partially inhibited cell infiltration. Intracameral injection of PAF scarcely
      induced cell infiltration but the reaction with EIU was accelerated by
      intracameral injection of a small amount of PAF. CONCLUSIONS: These results
      suggest that PAF has weak direct activity on cell infiltration in intraocular
      inflammation but enhances intraocular inflammation.

PMID- 9617546
TI  - Self-assessment of the quality of vision: association of questionnaire score with
      objective clinical tests.
AB  - PURPOSE: To investigate the association of a quality of life-visual function
      questionnaire with an objective clinical test of visual function. METHODS: We
      have developed a questionnaire to assess self-reported visual satisfaction in
      ophthalmic patients suffering from chronic eye conditions causing visual
      impairment. The questionnaire was administered to 120 patients suffering from age
      related cataract, chronic open angle glaucoma, age-related macular degeneration,
      branch retinal vein occlusion, and presbyopia or minor refractive defects. All
      the participants also underwent determination of visual acuity, contrast
      sensitivity, glare, and visual field. RESULTS: The questionnaire has a good
      reproducibility, a high internal consistency, and is able to discriminate between
      the different groups of patients. The total questionnaire score is significantly
      associated with the results of all visual function tests with the exception of
      glare. When entered into a multiple linear regression model, near visual acuity
      and contrast sensitivity are still considerably associated with the total
      questionnaire score. The psychological attitude of the patient towards his/her
      health problem is also associated with the total average score. CONCLUSIONS:
      Overall, the model explains 49% of the variance in the average questionnaire
      score.

PMID- 9617547
TI  - Injury of stromal fibroblasts induces phosphorylation of focal adhesion proteins.
AB  - PURPOSE: The extracellular matrix serves as a structural support for the corneal
      stroma and mediates signaling events that regulate the intracellular environment
      of stromal keratocytes. We hypothesize that adhesion and injury mediate signal
      transduction events causing the phosphorylation of tyrosine residues of specific
      adhesion proteins and that phosphorylation is required for cellular adhesion and
      migration. METHODS: For the adhesion experiments; primary rabbit stromal
      fibroblasts were seeded and phosphorylation of tyrosine residues was followed
      from 1 min to 24 h. For the injury experiments, confluent primary cultures were
      rendered quiescent, wounded, and tyrosine phosphorylation was followed from 30 s
      to 6 h. The antibody (py-20) was used to detect proteins phosphorylated on
      tyrosine residues. We examined changes in the phosphorylation of focal adhesion
      kinase (FAK), paxillin and cortactin, using immunoprecipitation and Western blot
      analysis. RESULTS: In the adhesion experiments, the phosphorylation of a 68-kDa
      protein was detected after 1 min, and the phosphorylation of a 125-kDa protein
      was not detected until 15 min. These proteins were identified in re-probed blots
      as paxillin and FAK. In the injury experiments, FAK phosphorylation was detected
      within 30 s and remained elevated for 6 h when cells were cultured on
      fibronectin. Both FAK and paxillin phosphorylation were prominent after injury,
      but unlike FAK phosphorylation, paxillin phosphorylation decreased over time.
      Phosphorylation was prominent at the wound margin. After wound closure, it
      returned to background levels. Tyrosine kinase inhibitors, genistein and
      herbimycin, decreased the number of adherent cells and altered the rate of cell
      migration after injury, compared to control (DMSO alone). CONCLUSION: The results
      indicate that injury and cell-matrix interaction mediate the phosphorylation of
      specific adhesion proteins and that phosphorylation is required for wound repair.

PMID- 9617548
TI  - Modulation of basic fibroblast growth factor effect by retinoic acid in cultured
      retinal pigment epithelium.
AB  - PURPOSE: We investigated the effect of retinoic acid (RA) on basic fibroblast
      growth factor (bFGF)-stimulated proliferation of cultured human retinal pigment
      epithelial (hRPE) cells and of 125I-bFGF-binding to the bFGF plasma membrane
      receptors of hRPE. METHODS: Proliferation of hRPE cells in the presence of
      increasing concentrations of bFGF and bFGF + RA was measured by 3H-thymidine
      incorporation into hRPE cells. To characterize bFGF receptors, hRPE cells were
      incubated at 4 degrees C with 125I-bFGF in the presence or absence of heparin.
      RESULTS: Basic-FGF stimulated 3H-thymidine incorporation into hRPE cells in a
      dose-dependent manner. RA inhibited bFGF-stimulated 3H-thymidine incorporation in
      the presence or absence of heparin. Increasing concentrations of unlabeled bFGF
      decreased the binding of 125I-bFGF to hRPE cells. Scatchared analysis indicated
      the presence of high and low affinity binding sites for bFGF with an apparent
      affinity Kd of 50 pM and 330 pM, respectively, and a binding capacity (Bmax) of
      1.25 X 10(5) and 3.38 X 10(5) binding sites per cell. Inhibition of 125I-bFGF
      binding was also possible by the carboxyl-terminal region peptide fragment bFGF
      (106-120)-NH2, but not amino-terminal region peptide fragment bFGF-(1-24)-NH2.
      The addition of heparin to the medium during binding studies did not prevent RA
      from inhibiting binding of 125I-bFGF to hRPE cells. Scatchard analysis
      demonstrated that, in the presence of heparin, there is a decrease in the number
      of high affinity binding sites (from 1.12 +/- 0.11 x 10(5) to 0.7 +/- 0.03 x
      10(5) binding sites per cell, a reduction of 36.7 +/- 0.04%, n = 3, p < 0.05).
      There was no significant change in affinity constants. CONCLUSIONS: These results
      suggest that RA inhibits bFGF cell proliferation in hRPE cells by decreasing the
      bFGF receptor number.

PMID- 9617549
TI  - Characterization of Bsk mice: I. The Bsk mutation does not involve a
      recombination of cornea-specific keratin 12 and skin-specific hair keratin genes.
AB  - PURPOSE: Bsk (bare skin) is an autosomal dominant mutation linked to the Krt 1
      (type 1 keratin) locus of mouse chromosome 11. The adult Bsk mouse manifests hair
      loss and corneal opacity. To identify and characterize the keratin genes involved
      in this mutation, we examined the hypothesis proposing that the Bsk mutation
      might involve a recombination event between cornea-specific (K12) and hair
      specific (mHa 1, 2, 3 and 4) type I keratin genes. METHODS: The Bsk phenotype was
      examined by histochemical analysis, using light and electron microscopy. RFLP was
      used for their genotyping, and possible keratin gene expression was examined by
      immunohistochemical staining, Western analysis, RT-PCR and Northern
      hybridization. RESULTS: Northern hybridization, RT-PCR and Western blot analysis
      revealed that mHa 1, 2, 3 and 4 keratins are expressed in the skin, but not in
      cornea, whereas the expression of K12 is limited to the corneas of the Bsk mice.
      These data ruled out the hypothesis that Bsk phenotype results from a
      recombination event between K12 and mHa 1, 2, 3 and 4. Ultrastructural and
      biochemical analyses also indicated that Bsk does not involve negative dominant
      mutations of keratin 12, mHa 1, 2, 3 and 4, epidermal-specific keratin 10, or
      basal cell-specific keratin 14. Expression of an acidic 50 kD keratin, recognized
      by monoclonal antibody AK 2, was up-regulated in the injured corneas of normal
      mice as well as Bsk corneas. CONCLUSION: The gene linked to the Bsk mutation
      remains unknown. The pathological changes in the skin and corneas may be
      secondary to the loss of protecting hairs and lashes by an unknown mechanism.

PMID- 9617550
TI  - An immunohistochemical study of endothelin-1 in the human eye.
AB  - PURPOSE: Endothelin-1 (ET-1) is a potent vasoconstrictive and neural peptide that
      has been demonstrated to be present and functionally active and important in the
      eye. This study was undertaken to examine for the first time the cellular
      distribution of ET-1 in the whole human eye. METHODS: Twelve human eyes were
      examined by immunohistochemical staining of paraffin sections, using an anti-ET-1
      primary antibody and an ABC-detection system. RESULTS: Endothelin-1
      immunoreactivity (ET-1-IR) was detected primarily in the fibrovascular stroma of
      the iris, ciliary body and choroid, in the retinal blood vessels, the ciliary and
      optic nerves, and in the corneal and the non-pigmented ciliary epithelium.
      CONCLUSION: In the eye, ET-1-IR is present in fibrovascular, neural and
      epithelial structures. Changes in the distribution and concentration of ET-1 may
      be relevant to a variety of ocular diseases including diabetes mellitus,
      hypertension, sickle cell disease, optic neuritis, AION, papilledema, corneal
      ulcer, corneal epithelial dystrophy or after keratoplasty.

PMID- 9617551
TI  - Expression of transforming growth factor-beta s and their receptors by human
      retinal glial cells.
AB  - PURPOSE: To help test the hypothesis that transforming growth factor beta (TGF
      beta) may serve an autocrine function in the retina, we asked whether human
      Muller (glial) cells in culture express TGF-beta receptors, contain transcripts
      for various isoforms of this cytokine, and release TGF-beta s into the medium.
      METHODS: Using the reverse transcriptase-polymerase chain reaction (RT-PCR)
      technique with specific primers for TGF-beta 1, -beta 2 and -beta 3 precursors
      and for TGF-beta type I and type II receptors, we searched for mRNA transcripts
      expressed by cultured human Muller cells. Also, an ELISA assay allowed
      quantification of the levels of various TGF-beta s in medium exposed to these
      glial cells. RESULTS: Human Muller cells in culture express transcripts for both
      type I and type II TGF-beta receptors and also for TGF-beta 1 and TGF-beta 2. In
      conditioned medium, the concentration of TGF-beta 1 in the mature form was below
      detectable levels, and the total TGF-beta 1 was relatively low (mean = 252 pg/ml
      in confluent cultures). In contrast, the mean levels of mature (55 pg/ml) and
      total (2530 pg/ml) TGF-beta 2 were markedly higher. CONCLUSIONS: Our observations
      that cultured Muller cells contain mRNA coding for the TGF-beta 2 precursor,
      release TGF-beta 2 into the medium and express transcripts for both type I and
      type II TGF-beta receptors are consistent with the idea that this cytokine serves
      an autocrine function for these glia in the retina.

PMID- 9617552
TI  - Pathogenesis of immunoglobulin A nephropathy.

PMID- 9617553
TI  - Epidemiology and prevention.

PMID- 9617554
TI  - Angiotensin converting enzyme inhibitors in nondiabetic renal disease.
AB  - The class of antihypertensive agents that act by blocking angiotensin II has been
      shown in several experimental models to have the interesting ability to protect
      the kidney. In patients with nondiabetic renal disease, a number of controlled
      clinical trials have shown angiotensin converting enzyme inhibitors to achieve a
      better control of blood pressure and significantly reduce the rate of progression
      of renal failure in comparison with conventional agents. In addition, treatment
      with angiotensin converting enzyme inhibitors has helped to achieve new
      information on the optimal blood pressure target to be reached in order to
      protect the residual renal function maximally.

PMID- 9617555
TI  - Angiotensin converting enzyme gene polymorphisms and renal disease.
AB  - In the past year there has been a profusion of reports identifying a possible
      association between the insertion/deletion polymorphism of the angiotensin
      converting enzyme and renal diseases. Rather than clarifying the situation, it
      has become more difficult to interpret its significance owing to small sample
      sizes and concerns over methodology; hence, studies are frequently contradictory.
      Despite these concerns there is evidence for a role of this polymorphism in
      progressive renal disease. This review summarizes the major studies in this field
      and suggests future strategies that might be employed to identify useful genetic
      markers in nephrology, for which the angiotensin converting enzyme polymorphism
      has acted as an important paradigm.

PMID- 9617556
TI  - Chronic cyclosporine nephrotoxicity.
AB  - Cyclosporine has improved patient and graft survival rates in solid organ
      transplantation, and has been increasingly applied with considerable clinical
      benefit in the treatment of autoimmune diseases. However, the therapeutic
      benefits of immunosuppressive therapy for transplant and autoimmune indications
      have frequently been limited by the occurrence of chronic nephrotoxicity.
      Cyclosporine nephrotoxicity therefore remains an important clinical challenge.
      The clinical aspects and pathophysiology of chronic cyclosporine nephrotoxicity,
      which is characterized by a decrease in glomerular filtration rate, afferent
      arteriolopathy, and striped tubulointerstitial fibrosis, are reviewed. Insights
      gained from experimental models of chronic nephrotoxicity associated with
      tubulointerstitial fibrosis are presented to elucidate the pathophysiology.

PMID- 9617557
TI  - Homocysteine, lipoprotein(a) and fibrinogen: metabolic risk factors for
      cardiovascular complications of chronic renal disease.
AB  - High plasma concentrations of homocysteine, lipoprotein(a) and fibrinogen are
      accompanied by an increased risk for cardiovascular complications in the general
      population. All three parameters are markedly elevated in patients with renal
      disease, a group with a high prevalence and incidence of cardiovascular
      complications. This review discusses these parameters in such patients in
      relation to the occurrence of atherosclerotic complications.

PMID- 9617558
TI  - Renal immunology and pathology.

PMID- 9617559
TI  - The role of chemokines in tissue inflammation and autoimmunity in renal diseases.
AB  - Chemokines are an expanding family of chemoattractant polypeptides involved in
      the extravasation of leukocytes during the inflammatory process. This review
      highlights recent advances in the field, including the discovery of a new class
      of chemokines, and several novel receptors. In addition, the expanding role of
      chemokines in pathologic processes other than extravasation and their potential
      as therapeutic targets are discussed.

PMID- 9617560
TI  - Biology of ischemic and toxic renal tubular cell injury: role of nitric oxide and
      the inflammatory response.
AB  - Acute ischemic or toxic injury to the kidney induces alterations in the
      expression of many genes. Some of these molecular responses have been termed
      'maladaptive' because they exacerbate the tubular damage induced by the
      initiating insult. Some maladaptive responses include alterations in the activity
      of nitric oxide synthases and expression of cytokines and adhesion molecules that
      mediate an inflammatory response. This review focuses on the role of nitric oxide
      and inflammation in influencing the course of acute renal failure due to ischemic
      and toxic tubular injury.

PMID- 9617561
TI  - T-cell activation in autoimmune and inflammatory diseases.
AB  - Recent progress in experimental models and human genetic linkage studies have
      provided new insight into the pathogenesis of autoimmunity. Both antigen-specific
      and antigen-nonspecific signals are crucial in the development of autoimmune
      disease. Interestingly, several of the single gene loci that have been identified
      as potential causes of autoimmune disease encode molecules that regulate antigen
      nonspecific modulation of immunity. The focus of this review is the role of the
      opposing signals transduced by the CD28 and cytotoxic T-lymphocyte antigen-4
      receptors that bind the B7 costimulatory ligands. Recent studies suggest that
      CD28 signals activate T cells, whereas cytotoxic T-lymphocyte antigen-4 signals
      deactivate T cells. importantly, both signals contribute to the induction of
      autoimmunity and offer novel targets for future therapeutic strategies to treat
      autoimmune disease.

PMID- 9617562
TI  - Complement and complement inhibitors: their role in autoimmune and inflammatory
      diseases.
AB  - The role of complement in the pathogenesis of renal injury is now being confirmed
      with the use of knockout technology and specific inhibitors. Chronic injury,
      particularly of the tubules and interstitium, and local complement synthesis are
      emerging as potential additional targets for complement-based therapy. Strategies
      are being developed to prevent complement-induced injury both in transplant and
      in native kidneys.

PMID- 9617563
TI  - Immunotherapy for autoimmune and inflammatory renal diseases.
AB  - New treatments for autoimmune renal disease are required, and a developing
      knowledge of its underlying immunopathogenesis has identified sites where
      immunotherapy is likely to be effective. Experience with intravenous
      immunoglobulin and lymphocyte depletion by monoclonal antibodies in systemic
      vasculitis and systemic lupus erythematosus is awaiting confirmation by
      randomized trials. Treatments at or near clinical testing include monoclonal
      antibody blockade of leucocyte-endothelial interactions and CD40 mediated B-cell
      activation, and immunoablation with autologous stem-cell transplantation for more
      severe multisystem autoimmune disease.

PMID- 9617564
TI  - Pancreas and pancreas-kidney transplantation.
AB  - Pancreas transplantation consistently results in an insulin-independent
      normoglycemic state in insulin-dependent diabetic recipients. Registry data show
      insulin independence is achieved in 80% of simultaneous kidney and pancreas
      recipients, more than 70% of pancreas after kidney recipients, and more than 60%
      of nonuremic pancreas transplant alone recipients. Advances in immunosuppression
      and careful monitoring for rejection in conjunction with biopsies are largely
      responsible for improved results. However, complications do occur, and
      improvements in surgical technique and patient care continue to evolve.

PMID- 9617565
TI  - Epidemiology and prevention.

PMID- 9617566
TI  - Renal immunology and pathology.

PMID- 9617567
TI  - Detection, cDNA cloning and sequencing of canine interleukin 12.
AB  - In canine peripheral blood mononuclear cells (PBMC) the mRNAs coding for both
      subunits of canine interleukin 12 (IL-12) were identified using reverse
      transcription polymerase chain reaction (RT-PCR). Stimulation of canine PBMC with
      Staphylococcus aureus strain Cowan plus Concanavalin A for 5 h resulted in
      significant mRNA synthesis. Likewise, inactivated vaccinia virus induced IL-12
      mRNA synthesis, however with different kinetics. The complete nucleotide sequence
      for both IL-12 subunits was determined using rapid amplification of cDNA ends
      (RACE)-PCR and cloning of amplified specific cDNAs. Computer-aided amino acid
      (aa) sequence comparison of both canine IL-12 subunits revealed more than 80%
      identity with the amino acid sequences of six other mammalian species. Closest
      relationship was found to human, porcine, bovine and cervine IL-12. However, no
      reactivity was found with antibodies directed against human IL-12, when
      supernatants of stimulated canine PBMC were tested. Supernatants of canine PBMC
      stimulated for IL-12 release also induced interferon gamma (IFN-gamma) mRNA as
      detectable by RT-PCR; however, it was not clear whether IFN-gamma mRNA synthesis
      was due to an IL-12 specific effect or other stimuli. As to the stimulating
      effect of IL-12 on canine IFN-gamma mRNA synthesis, recombinant human IL-12 was
      found to be a good inducer. Since IL-12 is regarded a major regulatory molecule
      of T-cell-mediated immune response and cell growth our work on the cloning and
      sequencing of this cytokine from dogs lays the basis for future investigations on
      the biological and possible therapeutic role of canine IL-12.

PMID- 9617568
TI  - High expression in bacteria and purification of polymorphic mouse interleukin 2
      molecules.
AB  - Recently, besides the known mouse interleukin 2 (IL-2) molecule, six other IL-2
      alleles have been found in different mouse strains. In order to study their in
      vivo and in vitro biological activities large quantities are required. We cloned
      the corresponding IL-2 cDNAs into a pET7-7/BL21(DE3) bacterial system, a T7-RNA
      polymerase-dependent expression vector, producing between 30 to 100 mg of IL-2
      per litre of culture. The purification step is based on the resolution properties
      of the sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE)
      technique and the capability of the IL-2 to regain its activity after SDS
      denaturation. These purified IL-2 molecules supported the growth of an IL-2
      dependent cell line, CTL-L2, in a similar way to a commercial mouse IL-2 control.
      However, RF IL-2 allele, which is also expressed in NOD mice had a relatively
      lower growth activity in the CTL-L2 assay. These IL-2 molecules can be obtained
      in a purified form and totally recovered their activity after elimination of the
      SDS and 2-mercaptoethanol used in the extraction procedure.

PMID- 9617569
TI  - Activated human neutrophils express vascular endothelial growth factor (VEGF).
AB  - The neutrophil (PMN) influx in the acute inflammatory response is associated with
      a local increase in vascular permeability and oedema. Vascular endothelial growth
      factor (VEGF), a growth factor known to have potent vascular permeability
      enhancing properties in addition to being an endothelial cell mitogen and a chemo
      attractant for mononuclear cells, has previously been shown to be expressed by
      mononuclear cells and platelets, though PMN VEGF expression has not been
      reported. PMNs isolated from healthy adult volunteers (n = 16) were incubated for
      4 h at 37 degrees C in the presence of tumour necrosis factor alpha (TNF-alpha)
      (5 ng/ml) and serum opsonized zymozan (SOZ) (500 micrograms/ml). Supernatant VEGF
      levels were measured using a sandwich antibody capture immuno-assay. Median
      (interquartile range) VEGF levels were significantly increased in PMN
      supernatants following stimulation with both TNF-alpha [347 pg/ml (264-385
      pg/ml)] and SOZ [506 pg/ml (407-593 pg/ml)] compared with control values [78
      pg/ml (78-87 pg/ml)]. Time course experiments with SOZ stimulated PMNs showed
      that the majority of VEGF production occurred within the first hour (1 h mean
      VEGF level 318 pg/ml, 4 h mean VEGF level 451 pg/ml). RT-PCR studies showed that
      PMNs express mRNA for the two common VEGF splice variants, VEGF121 and VEGF165.
      PMN VEGF production may be central to the classic acute phase response to injury
      and the chemo-attraction of other leukocytes to the source of injury.

PMID- 9617570
TI  - Tumour necrosis factor alpha alters the expression of connexin43, connexin40, and
      connexin37 in human umbilical vein endothelial cells.
AB  - Tumour necrosis factor alpha (TNF-alpha) plays an important role in orchestrating
      inflammatory responses with the vascular endothelium as main target cell type,
      and was found to promote migration of endothelial cells, as occurs in wound
      healing processes. Substantial evidence exists that endothelial cell migration in
      wound healing is related to changes in cell coupling by means of gap junctions.
      Gap junctions are agglomerates of cell-to-cell channels that allow direct
      electrical and metabolic communication between cells. The authors have
      investigated whether TNF-alpha alters the expression of gap junction proteins
      (connexins, Cx) between human umbilical vein endothelial cells (HUVEC), thereby
      changing the extent of intercellular communication, as measured by dye coupling.
      Under control conditions, Cx43, Cx40, and Cx37 protein and mRNA were present in
      HUVEC. After exposure to 0.5 nM TNF-alpha for 48 h, however, the authors were no
      longer able to detect Cx37 and Cx40 protein, whereas Cx43 levels seemed unaltered
      but showed more perinuclear staining. After 24 and 48 h exposure to TNF-alpha,
      levels of Cx37 and Cx40 mRNA, were reduced, while the level of Cx43 mRNA remained
      unaltered, suggesting transcriptional regulation. If TNF-alpha was removed from
      the medium, Cx37 and Cx40 expression was restored within 24 h. The modulation of
      connexin expression by TNF-alpha resulted in a decrease in dye coupling of 40%.

PMID- 9617571
TI  - PGE2 inhibits IL-2 and IL-4-dependent proliferation of CTLL-2 and HT2 cells.
AB  - The cytotoxic T cell line CTLL-2 and the T helper cell line HT2 proliferate in
      response to interleukin 2 (IL-2) or IL-4 without requiring stimulation by antigen
      through the T cell receptor and therefore lend themselves for studies of IL-2-
      and IL-4-dependent proliferation and signalling through their cognate receptors.
      Here we have used CTLL-2 and HT2 cells to investigate the effect of the
      inflammatory mediator prostaglandin E2 (PGE2) on IL-2- and IL-4-dependent
      proliferation. PGE2 inhibited IL-2- as well as IL-4-dependent proliferation of
      both CTLL-2 and HT2 cells, with IL-4-dependent proliferation being more sensitive
      than IL-2-dependent proliferation and CTLL-2 cells being more sensitive than HT2
      cells. A quantitative dose-effect analysis revealed a two-step increase of
      inhibition (around 10(-10) M and 10(-5) M PGE2) for all combinations of cells and
      cytokines approaching 100% at high concentrations of PGE2. The data suggest that
      even in cases where synthesis of IL-2 and IL-4 is differentially affected by
      PGE2, IL-2- and IL-4-dependent T cells may still be similarly sensitive to PGE2
      by way of their cytokine responsiveness. Furthermore, the effects of PGE2 may be
      mediated by more than one functional binding site or receptor subtype. PGE2
      levels are an important consideration when CTLL-2 and HT2 cells are used for the
      measurement of IL-4 and IL-2.

PMID- 9617572
TI  - IL-1 beta and TNF-alpha suppress apolipoprotein (apo) E secretion and apo A-I
      expression in HepG2 cells.
AB  - The effect of cytokines on apolipoprotein E (apo E) production and secretion was
      investigated in a human hepatoma cell line HepG2. Incubation of HepG2 cells with
      interleukin 1 beta (IL-1 beta) or tumour necrosis factor alpha (TNF-alpha) for 48
      h resulted in a significant dose-related decrease of apo E concentration in the
      culture medium, while intracellular apo E content increased without change in
      mRNA level. In contrast, IL-1 beta and TNF-alpha decreased both intracellular and
      medium apo A-I. Elution profiles of cholesterol and apolipoproteins revealed that
      apo E was present in apo E-rich high density lipoprotein (HDL) fraction and apo A
      I was in apo E-rich HDL and small HDL fractions. IL-1 beta and TNF-alpha
      decreased both apo E and apo A-I in these fractions. The present results suggest
      that IL-1 beta and TNF-alpha suppress hepatic apo A-I expression and secretion
      but not expression of apo E, which could contribute to the abnormal lipid
      metabolism in certain cytokine-mediated inflammatory diseases.

PMID- 9617573
TI  - Differential motogenic and biosynthetic response of fetal and adult skin
      fibroblasts to TGF-beta isoforms.
AB  - Data are presented in this communication comparing fetal and adult fibroblasts
      with respect to the effects of transforming growth factor beta (TGF-beta)
      isoforms (-beta 1, -beta 2 and -beta 3) on cell migration and hyaluronan (HA)
      synthesis. Cell migration was assessed on three-dimensional native type I
      collagen substrata. Fetal and adult cells differed in terms of their motogenic
      response to the three TGF-beta isoforms in a manner which was modulated by cell
      density, i.e.: (1) the migration of subconfluent fetal cells was unaffected by
      TGF-beta 1 and -beta 2, but inhibited by TGF-beta 3, whilst the migration of
      subconfluent adult cells was inhibited by all three isoforms, and (2) the
      migration of confluent fetal cells was inhibited by all three TGF-beta isoforms,
      whilst the migration of confluent adult cells was unaffected by TGF-beta 1 and 
      beta 2, but stimulated by TGF-beta 3. This diverse pattern of motogenic response
      to the three TGF-beta isoforms was paralleled by similar effects on HA synthesis
      (i.e. inhibition, no effect or stimulation). Linear regression analysis revealed
      a significant correlation between cell migration and total HA synthesis (r2 =
      0.861; P < 0.0001). Gel filtration chromatography of cell-produced HA indicated
      that the effects of TGF-beta isoforms on total HA synthesis reflected alterations
      in the relative production of high molecular mass species (M(r) > 10(6)). Taken
      together with previously published data, these observations indicate that (1)
      fetal and adult fibroblasts exhibit distinct responses to the three TGF-beta
      isoforms with respect to both cell migration and HA synthesis, (2) cellular
      response to the TGF-beta isoforms is modulated by cell density, and (3) TGF-beta
      3 is the only isoform which stimulated cell migration and HA synthesis (with
      confluent adult cells).

PMID- 9617574
TI  - BALB/c 3T3 cells co-expressing FGF-2 and soluble FGF receptor acquire
      tumorigenicity.
AB  - The physiological significance of the soluble fibroblast growth factor (FGF)
      receptors is not clear yet although they are present in blood, vitreous fluid and
      in the extracellular matrix of vascular endothelial cells. A hypothesis that they
      might help FGF-2 release from cells is very interesting because FGF-2 does not
      have clear secretion signal and the mechanism of the secretion of FGF-2 is still
      unclear. Single overexpression of FGF-2 is related neither to the secretion
      potential of the molecule nor to the tumorigenicity of the cells. In this report,
      BALB/c 3T3 cells transformed with the full length of human FGF-2 cDNA are further
      transformed with the cDNA coding the extracellular domain of human FGF receptor
      1. The obtained transformants co-expressing FGF-2 and soluble FGF receptor are
      highly tumorigenic in nude mice, while the parental cells do not show any
      tumorigenicity. In the conditioned medium of the double-transformants, FGF-2 is
      immunologically detected. These results suggest that naturally produced soluble
      form of FGF receptor supports the release of FGF-2 from the cells and that over
      expression of these two molecules leads to induce the malignant tumours in vivo.

PMID- 9617575
TI  - Oncostatin M-specific receptor expression and function in regulating cell
      proliferation of normal and malignant mammary epithelial cells.
AB  - Oncostatin M (OSM) is a cytokine produced by activated T lymphocytes and
      macrophages. OSM is structurally and functionally related to leukaemia inhibitory
      factor (LIF), another cytokine in the interleukin 6 (IL-6) family. The biological
      activities of OSM are mediated through two types of receptor complexes, the
      LIF/OSM shared receptor (type I) and OSM-specific receptor (OSM-R, type II),
      which is composed of gp130 as a binding subunit and a newly identified affinity
      conversion subunit, OSM-R beta. Previous research conducted in the authors'
      laboratory has shown that OSM inhibits the growth of several breast cancer cell
      lines. To investigate whether OSM has a similar effect in primary normal human
      mammary epithelial (HME) cells, the activity of OSM in HME cells derived from
      four donors was examined. OSM produced a dose-dependent inhibition of DNA
      synethesis in these cells. In order to determine the receptor subtypes mediating
      OSM activity in HME and breast cancer cells, flow cytometry analysis using anti
      gp130mAb and anti-OSM-R beta mAb was performed. In these studies, the authors
      were able to examine expressions of gp130 and OSM-R beta. In addition,
      quantitative RT-PCR assays were conducted to measure expressions of the mRNAs of
      the subunits for type I and type II OSM receptor. The results show that HME cells
      and most breast cancer cell lines express both the type I and the type II OSM
      receptors. However, type II, OSM-specific receptors are expressed at a higher
      levels than type I, OSM/LIF shared receptors. Accordingly, we compared the growth
      regulatory activities of OSM with LIF in HME cells and in breast cancer cells. In
      contrast to the inhibitory activity of OSM, LIF stimulated the growth of breast
      cancer cells, whereas it had no effect on normal mammary epithelial cell growth.
      Together, these data suggest that OSM plays an inhibitory role in normal and
      malignant mammary epithelial cell growth in vitro. OSM activity is mediated by
      the OSM-specific receptor (type II), not by the OSM/LIF shared receptor.

PMID- 9617576
TI  - Plasma leukaemia inhibitory factor, interleukin 6 and soluble interleukin 6
      receptor levels during cardiopulmonary bypass with extracorporeal circulation.
AB  - In this study the authors assessed plasma leukaemia inhibitory factor (LIF),
      interleukin 6 (IL-6) and soluble IL-6 receptor (sIL-6R) concentrations in 28
      patients undergoing coronary artery bypass graft (CABG) with extracorporeal
      circulation (ECC). Plasma IL-6 levels increased during ECC, reaching a 33-fold
      increase 6 h after surgery as compared to pre-operative values. In contrast,
      plasma sIL-6R and LIF concentrations did not vary significantly during cardiac
      surgery. Thus, LIF is not implicated in the haematological changes and in the
      inflammatory syndrome observed after CABG. Despite the fact that LIF and IL-6
      exhibit several common biological activities, the production of these two
      cytokines is differently regulated during cardiac surgery with ECC. Plasma IL-6
      levels increased during cardiac surgery while sIL-6R levels did not changed.
      These data contrast with the decreased sIL-6R concentrations with concomitantly
      high IL-6 levels in patients with sepsis syndrome suggesting that inflammatory
      reactions in sepsis and after cardiopulmonary bypass are triggered by different
      mechanisms.

PMID- 9617577
TI  - Diurnal rhythms of pro-inflammatory cytokines: regulation by plasma cortisol and
      therapeutic implications.
AB  - Clinical features of certain immuno-inflammatory disorders such as rheumatoid
      arthritis and asthma exhibit diurnal fluctuation, which could be related to
      diurnal rhythmicity of pro-inflammatory cytokine production. To investigate the
      latter, the authors performed measurements of lipopolysaccharide (LPS)-stimulated
      whole blood, interferon gamma (IFN-gamma), tumour necrosis factor alpha (TNF
      alpha), interleukin 1 (IL-1) and IL-12 production in 13 healthy volunteers over
      24 h. These cytokines exhibited distinct diurnal rhythms that peaked in the early
      morning and were inversely related to the rhythm of plasma cortisol. Elevation of
      plasma cortisol within the physiological range by administration of cortisone
      acetate, 25 mg at 21.00, markedly suppressed IFN-gamma, TNF-alpha, IL-1 and IL-12
      production, but not the later early morning rise of endogenous plasma cortisol.
      Suppression of cytokine production was temporally dissociated from changes in
      numbers of circulating mononuclear cells. Regulation of pro-inflammatory cytokine
      production by plasma cortisol has potential therapeutic implications. In contrast
      to standard schedules, a small, late evening, dose of glucocorticoid to suppress
      the diurnal increase in pro-inflammatory cytokine production could alleviate
      early morning inflammatory symptoms and minimize side-effects.

PMID- 9617578
TI  - The effects of psychological stress on humans: increased production of pro
      inflammatory cytokines and a Th1-like response in stress-induced anxiety.
AB  - There is some evidence that, in humans and experimental animals, psychological
      stress may suppress or enhance immune functions, depending on the nature of the
      stressor and the immune variables under consideration. The possibility that
      psychological stress may affect the production of pro-inflammatory and
      immunoregulatory cytokines was investigated in 38 medical students, who had blood
      samplings a few weeks before and after as well as one day before an academic
      examination. Psychological stress significantly increased the stimulated
      production of tumour necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), IL
      1 receptor antagonist (IL-1Ra), interferon gamma (IFN-gamma) and IL-10. Students
      with high stress perception during the stressful condition had a significantly
      higher production of TNF-alpha, IL-6, IL-1Ra and IFN-gamma than students with a
      low-stress perception. Students with a high anxiety response had a significantly
      higher production of IFN-gamma and a lower production of the negative
      immunoregulatory cytokines, IL-10 and IL-4, than students without anxiety. These
      findings suggest that, in humans, changes in the production of the pro
      inflammatory cytokines, TNF-alpha, IL-6 and IFN-gamma, and negative
      immunoregulatory cytokines, IL-10 and IL-4, take part in the homeostatic
      responses to psychological stress and that stress-induced anxiety is related to a
      T-helper-1-like response.

PMID- 9617579
TI  - Characterization of a 14 kDa plant-related serine protease inhibitor and
      regulation of cytotoxic activity in earthworm coelomic fluid.
AB  - We have purified and characterized the serine protease inhibitor activity
      contained in the coelomic fluid of the earthworms, Eisenia. Serine protease
      inhibitor activity was stable between pH3 and 9.5, not flocculable by pH 3.0 and
      resistant to 100 degrees C for 15 min. or to 4 degrees C for 24 h. Ten microL of
      coelomic fluid was sufficient to inhibit in vitro the protease activity of 0.12
      microgram of trypsin. Injection of living bacteria into earthworms resulted in
      increased serine protease activity 1-2 days post-injection, and increased serine
      protease inhibitor activity on day 4, suggesting that serine protease inhibitor
      is responsible for serine protease neutralization. Purified to homogeneity by
      affinity chromatography on trypsin, the serine protease inhibitor of Eisenia is a
      monomer of 14 kDa. Its partial NH2 amino acid sequence revealed a basic
      hydrophobic fragment which shared 68-75% homologies and 47-60% identities with
      several plant serine protease inhibitors. Eisenia cytotoxic activity due to the
      two fetidins of 40 and 45 kDa was stimulable in vitro by several serine
      proteases. Incubation with soybean trypsin inhibitor variant a (STIa) resulted in
      less cytotoxicity. The inhibitory effect occurred only when STIa was added before
      cell disruption. Interpretative cytotoxic scheme involving the release of
      intracellular cytotoxic proteins, intracellular trypsin-like activator and
      extracellular serine protease inhibitor suggests regulatory mechanisms for
      cellular/humoral immune system of earthworms.

PMID- 9617580
TI  - Isolation and characterization of earthworm hemolysins and agglutinins.
AB  - Hemolytic activity in coelomic fluid of Eisenia fetida (ECF) is due to three
      proteins H1, H2, H3 with molecular weights of 46, 43 and 40 kD, respectively.
      These proteins were isolated by preparative PAGE. H1 and H2 were shown to be
      stable in SDS and alpha-2-ME whereas H3 splits into two fragments with molecular
      weights of 18 and 21 kD after SDS treatment. IEF indicates that each protein
      consists of different isoforms with pIs between 5.1 and 6.2 H3 was demonstrated
      to be a bifunctional protein that can lyse and agglutinate erythrocytes. At 56
      degrees C hemolytic activity of all three proteins was inactivated, but the
      agglutination activity of H3 was stable. Intracoelomic injection of erythrocytes
      reduced the number of hemolysins from three to two. Monospecific antisera were
      raised against the isolated hemolysins H1,2 and 3. The use of these antibodies
      and of carbohydrates as inhibitors of the biological activity of the molecules
      demonstrates the close structural relationship of agglutinins and hemolysins in
      the CF of E. fetida.

PMID- 9617581
TI  - Lysozyme and antiprotease activity in the lesser octopus Eledone cirrhosa (Lam.)
      (Cephalopoda).
AB  - Antiprotease and lysozyme activities were detected in various tissue samples
      including the haemocytes and haemolymph of Eledone cirrhosa. Injection of live
      Vibrio anguillarum caused an increase in lysozyme activity in the branchial heart
      over 48 hours and a decrease in the lysozyme activity of haemocytes over 24
      hours. Haemocytes from control PBS injected animals demonstrated increased
      lysozyme levels 4 hours after injection whereas it decreased after the injection
      of live bacteria in PBS. The lysozyme activity of the haemolymph was not affected
      by these procedures. Bacteria injections had no effect on the antiprotease
      activity of the organ samples but increased the antiprotease activity of the
      haemocytes compared to controls in the 4 h samples. Haemolymph antiprotease
      activity decreased at a greater rate following bacteria injection than in control
      PBS injected animals. Haemocyte numbers/ml increased for both the control and
      bacteria injected animals with a greater increase demonstrated for the bacteria
      injected animals in the 4 h sample. Concomittant with the increase in the numbers
      of circulating haemocytes live V. anguillarum were cleared from the circulation
      of E. cirrhosa in less than 4 hours.

PMID- 9617582
TI  - Integrin-like RGD-dependent binding mechanism involved in the spreading response
      of circulating molluscan phagocytes.
AB  - Circulating phagocytic cells (hemocytes) of the snail Biomphalaria glabrata,
      intermediate host of the human blood fluke Schistosoma mansoni, were treated with
      the tetrapeptide, arg-gly-asp-ser (RGDS), an integrin-specific adhesion
      inhibitor, and assessed for their ability to adhere and spread on uncoated and
      snail plasma protein-coated glass slides. Although cells were capable of
      adherence, RGDS significantly inhibited the spreading ability of hemocytes in
      both a time and RGDS concentration-dependent fashion regardless of plasma protein
      coating. The inhibition of hemocyte spreading by RGDS was a specific response,
      since treatment of cells with a glutamic acid-substituted control peptide (RGES)
      did not exert the same inhibitory effect. A comparison of RGDS-responses between
      hemocytes of two strains of B. glabrata, one resistant (R; 13-16-R1 strain) and
      the other susceptible (S; NMRI strain) to infection by S. mansoni, revealed
      several snail strain-specific differences. At concentrations of 0.5 mM RGDS, R
      snail hemocyte spreading was unaffected, whereas a significant depression of
      spreading was seen in cells of the S snail. Moreover, we observed that R strain
      hemocytes spread more rapidly on homologous plasma-coated surfaces than the S
      snail strain following peptide pretreatment and removal. These data suggest that
      hemocytes from S and R snails may differ either in the number of RGDS-binding
      receptors or in their affinity for the RGDS peptide. In order to identify the
      type(s) of integrin-like RGD-binding receptors that may be present on the surface
      of snail immunocytes, washed hemocytes were placed on various mammalian
      extracellular matrix proteins and evaluated for their spreading function in the
      presence of specific or non-specific peptides. Hemocyte aggregation or clumping
      was observed on all test protein substrates, and this aggregation behavior was
      specifically inhibited by RGDS. Thus, RGD-binding receptors appear to play a
      critical role in cellular motility on matrix-coated surfaces and/or cell-cell
      binding. Our data provide functional evidence for an integrin-like receptor on
      circulating phagocytes of snails, and for an RGD-binding mechanism involved in
      cell-substrate interactions.

PMID- 9617583
TI  - A comparison of the chemiluminescent response of Crassostrea virginica and Morone
      saxatilis phagocytes to zymosan and viable Listonella anguillarum.
AB  - If reactive oxygen species (ROS) produced by hemocytes of the eastern oyster,
      Crassostrea virginica, impart bactericidal activity, exposure of hemocytes to
      bacteria should result in increased ROS generation. In an earlier study, this
      hypothesis was tested using luminol- and lucigenin-augmented chemiluminescence
      (CL) to measure ROS production. The bacterium Listonella anguillarum did not
      stimulate a net increase in hemocyte-derived CL, and it was suggested that
      bacterial antioxidants might suppress hemocyte CL. In the present study a
      comparison was made, under identical assay conditions, of the zymosan- and
      bacteria-enhanced luminol CL produced by eastern oyster hemocytes and by striped
      bass (Morone saxatilis) macrophages, for which L. anguillarum has been shown to
      be a stimulus in CL reactions. The response to zymosan produced by bass
      phagocytes was two orders of magnitude greater than that generated by eastern
      oyster hemocytes. Whereas an increase in net ROS production was not evident when
      oyster hemocytes were exposed to L. anguillarum, significant stimulation of
      striped bass macrophage-derived CL occurred. These data suggest that striped bass
      macrophages have a greater capacity to generate ROS than oyster hemocytes,
      enabling them to surpass the antioxidant capability of L. anguillarum and produce
      a luminol CL response.

PMID- 9617584
TI  - Indications for a distinct putative T cell population in mucosal tissue of carp
      (Cyprinus carpio L.).
AB  - A monoclonal antibody against carp intestinal T cells (WCL38; of IgM class) was
      produced by immunization of mice with isolated membrane molecules of carp
      intestinal intraepithelial lymphoid cells. Flow cytometric analysis showed that
      WCL38 reacted with 50-70% of the lymphoid cells isolated from intestine, gills or
      skin, with less than 6% of lymphoid cells isolated from thymus, head kidney or
      spleen and with a negligible number of PBL. WCL38+ cells were abundant in the
      intestinal epithelium and less numerous in the lamina propria. Immunogold
      labelling confirmed that WCL38 reacted with lymphoid cells; in gills and skin
      some of them have the morphology of large granular lymphoid cells. Immunochemical
      analysis showed that WCL38 reacted with dimeric membrane molecule on mucosal
      lymphoid cells with an Mr of 76 kDa, consisting of two 38 kDa subunits. WCL 38+
      lymphoid cells are postulated to T cells, since WCL38 does not react with B
      cells, macrophages or non-specific cytotoxic cells. In conclusion, like higher
      vertebrates, carp seem to have a distinct (Putative) T cell population in their
      mucosal tissues.

PMID- 9617585
TI  - Effects of Cyclosporin A on skin graft rejection in Xenopus.
AB  - In Xenopus, it has been shown that semi-xenogeneic adult skin grafts usually
      render donor-specific tolerance to perimetamorphic larvae, while these skin
      grafts are never accepted in adults. The mechanisms operating in this tolerance
      induction are largely unclear. The present investigation was planned to test
      whether lower responsiveness of larvae to non-self antigens could be ascribable
      to perimetamorphic tolerance induction. We tried to induce tolerance in adults by
      treating them with Cyclosporin A (CsA), which is known to decline the immune
      system in mammals. The results showed that CsA-treated adults could never be
      rendered tolerant to semi-xenogeneic skin grafts, although the grafts were not
      rejected as long as the treatment was continued. We have also proposed a possibly
      different mechanisms for the rejection of semi-xenogeneic skin grafts and of full
      xenogeneic skin grafts.

PMID- 9617586
TI  - Axolotl (Ambystoma mexicanum) lymphocytes produce and are growth-inhibited by
      transforming growth factor-beta.
AB  - Recombinant (r)TGF-beta 5, an isoform of TGF-beta thus far identified only in the
      frog, Xenopus' laevis, inhibited phytohemagglutinin (PHA)-induced mitogenesis of
      salamander (axolotl) splenocytes and thymocytes, and T cell growth factor-induced
      proliferation of splenic lymphoblasts. This inhibition could be reversed by
      incubating (r)TGF-beta 5 with an anti-TGF-beta 5 antibody, but not with an
      antibody directed against TGF-beta 2, another Xenopus-produced TGF-beta isoform.
      Acid-treated supernatants from cultures of PHA-stimulated axolotl splenocytes
      (PHA-SNs) inhibited proliferation of mink lung fibroblasts (MLF), cells whose
      growth is sensitive to all known isoforms of TGF-beta. This inhibition was
      reversed by incubating the supernatants with the anti-pan-specific TGF-beta
      antibody which neutralizes TGF-beta 1, TGF-beta 2, TGF-beta 3 and TGF-beta 5.
      This inhibition was unaffected by antibodies that specifically neutralize either
      TGF-beta 1, TGF-beta 2, TGF-beta 3 or TGF-beta 5. Acid-treated axolotl PHA-SNs
      also inhibited proliferation of PHA-stimulated freshly harvested axolotl spleen
      cells. Once again, this inhibition could be reversed by treating supernatants
      with an anti-pan-specific TGF-beta antibody but not with anti-TGF-beta 2 or anti
      TGF-beta 5 antibodies. All these data are consistent with the hypothesis that
      axolotl lymphocytes secrete a previously unknown TGF-beta isoform.

PMID- 9617587
TI  - Age-dependent phagocytosis and bactericidal activities of the chicken heterophil.
AB  - Chicks are most susceptible to Salmonella infection during the first 4 days post
      hatch. In poultry, one of the primary cells in the innate immune response to
      early bacterial invasion by Salmonella is the heterophil. Previous studies using
      a granulocytopenic chicken model in more mature birds demonstrated the
      significant role heterophils have in the defense mechanism against Salmonella. In
      the past studies have also shown the efficiency of heterophils from 3- to 5-week
      old chickens to phagocytose and kill Salmonella as compared to monocytes. During
      the present study, we investigated the phagocytic and bactericidal activities of
      heterophils from chickens during the first 7 days post-hatch to evaluate whether
      decreased heterophil function plays a role in the susceptibility of young chicks
      to Salmonella infections. Peripheral blood counts demonstrated no differences in
      the percentages of heterophils during the first week post-hatch. The phagocytic
      index of the heterophil did not change on day 1 or day 4, but doubled by day 7
      (day 1, 30.69; day 4, 33.99; day 7, 60.46). Interestingly, the bactericidal
      activity of the heterophils from all three age groups efficiently killed
      Salmonella enteritidis. Based on this data, we conclude that a relationship
      exists between the age of the chick, the functional activity of the heterophil,
      and the susceptibility to organ invasion by Salmonella.

PMID- 9617588
TI  - Compartments within the lymph node cortex of calves and adult cattle differ in
      the distribution of leukocyte populations: an immunohistochemical study using
      computer-assisted morphometric analysis.
AB  - The combination of an immunohistochemical technique and a panel of monoclonal
      antibodies was used to investigate the presence of leukocyte populations in the
      distal jejunal lymph node of 3-4 week old calves and adult cattle. The
      application of computer-assisted morphometric analysis enabled information to be
      obtained on the distribution of leukocyte populations in lymphoid compartments of
      the lymph node cortex. Semi-quantitative estimates of the areas of staining in
      histological sections showed that calves possessed significantly fewer B-cells
      and CD4+ cells in the outer cortex and significantly fewer T-cells (CD4+, CD8+
      and gamma delta T-cells) in the deep cortex. These findings were interpreted to
      be a possible consequence of immunosuppression resulting from the passive
      transfer of maternal immunity in colostrum. The presence of some B-cell follicles
      in the region defined as the deep cortex suggested the on-going differentiation
      of this predominantly T-cell compartment. The larger presence of interdigitating
      cells (IDC) in the deep cortex of calves than adults was suggested by
      significantly larger CD1+ populations and it was argued that this could be the
      result of the confrontation with exogenous antigen faced by calves in early
      postnatal life. Antigen presenting populations, pan MHC II+ and MHC II DQ+
      populations, were increased in all compartments of calf lymph nodes but were not
      significantly different from the populations in adult lymph nodes. Variance
      component analysis of the data generated in the present study showed that the
      image analysis technique was an effective and statistically powerful approach to
      investigate leukocyte populations within the specific microenvironments of the
      lymph node.

PMID- 9617590
TI  - Digoxin use in congestive heart failure. Current status.
AB  - The use of digitalis in congestive heart failure with normal sinus rhythm is
      still debated. While older uncontrolled, withdrawal studies from 1969 to 1983
      provided incomplete data, with poorly documented clinical status and poor
      haemodynamic and exercise data, some patients did improve clinically when
      digitalis treatment was utilised. Randomised, double-blind, placebo-controlled
      trials from 1977 to 1991 were of better quality but still short in duration, with
      small sample sizes and still with incomplete haemodynamic and exercise data. In
      1993, the Prospective Randomised Study of Ventricular Failure and Efficacy of
      Digoxin (PROVED) and Randomised Assessment of Digoxin on Inhibitors of the
      Angiotensin-Converting Enzyme (RADIANCE) study, followed in 1997 by the Digitalis
      Investigation Group (DIG) trial, documented that digoxin prevents clinical
      deterioration and hospitalisations, and improves exercise tolerance and left
      ventricular function, but has no effect on survival. A substudy of the DIG trial
      showed no detrimental effect of digoxin on survival in patients with ejection
      fraction (EF) of > 45%, i.e. left ventricular (LV) diastolic dysfunction.
      Therefore, digoxin appears to be the first inotrope with no detrimental effect on
      survival in heart failure. In addition, the neurohormonal effect of digoxin has
      been documented, and is possibly present with dosages even lower than 0.25 mg.
      Finally, it has been determined that patients with only mild heart failure do
      obtain documented benefit from administration of this drug.

PMID- 9617589
TI  - The future use of complement inhibitors for the treatment of neurological
      diseases.
AB  - A chronically activated immune system can kill host cells, and accumulating
      evidence suggests that this mechanism plays an important role in many
      degenerative diseases. It may be of importance in CNS conditions such as
      Alzheimer's disease, ischaemia and even Parkinson's disease, as well as in
      peripheral disorders such as myocardial ischaemia and xenotransplantation. The
      complement system plays a key role in the immune reaction and can kill host
      tissue directly, by action of the membrane attack complex (MAC) of complement, or
      indirectly, through activation of macrophages which produce abundant amounts of
      oxygen radicals and other potentially toxic products. Endogenous regulators for
      many steps in the complement cascade have been identified, and these and some
      analogues are being explored as possible agents for the prevention of the toxic
      effects of complement activation. Numerous reports have attested to the
      protective effects of such inhibitors in animal models of immune disorders,
      particularly of transplant rejection and ischaemia-reperfusion injury. There have
      been a few clinical trials in peripheral disorders and, although not yet tried in
      neurological disease, it seems probable that this general approach will lead to
      therapeutic agents capable of specific modulation of the central immune response.

PMID- 9617591
TI  - Childhood immunisation today.
AB  - Better knowledge of the pathogenesis of infections and host responses, and
      progress in biotechnology, have paved the way for new vaccines. In spite of rapid
      progress with several vaccine candidates, overoptimism is, however, not
      warranted. There is usually several years' delay before the new vaccine from the
      laboratory is available in practice. Acellular pertussis vaccine and rotavirus
      vaccine are examples of new vaccines that are currently being introduced;
      varicella, inactivated polio, and hepatitis B vaccines have been suggested for
      use in a new and more efficient way. In order to keep up high motivation among
      families and thus high vaccination coverage, more emphasis must be put on
      information about vaccines, their properties and proper use. Economic analyses
      are becoming more important in the decision to use new vaccines. Therefore, cost
      benefit, cost-effectiveness and cost-utility analyses need to be conducted so
      that a basis can exist for determining a rational policy.

PMID- 9617592
TI  - Current drug treatment strategies for disseminated intravascular coagulation.
AB  - Disseminated intravascular coagulation (DIC) can be caused by a variety of
      diseases. Experimental models of DIC have provided substantial insight into the
      pathogenesis of this disorder, which may ultimately result in improved treatment.
      Disseminated coagulation is the result of a complex imbalance of coagulation and
      fibrinolysis. Simultaneously occurring tissue factor-dependent activation of
      coagulation, depression of natural anticoagulant pathways and shutdown of
      endogenous fibrinolysis all contribute to the clinical picture of widespread
      thrombotic deposition in the microvasculature and subsequent multiple organ
      failure. Cornerstone for the treatment of DIC is the optimal management of the
      underlying disorder. At present, specific treatment of the coagulation disorders
      themselves is not based on firm evidence from controlled clinical trials. Plasma
      and platelet transfusion are used in patients with bleeding or at risk for
      bleeding and low levels of coagulation factors or thrombocytopenia. The role of
      heparin and low molecular weight heparin is controversial, but their use may be
      justified in patients with active DIC and clinical signs of extensive fibrin
      deposition such as those with meningococcal sepsis. There is some evidence to
      indicate that low molecular weight heparin is as effective as unfractionated
      heparin but may be associated with a decreased bleeding risk. Antithrombin III
      (AT III) replacement appears to be effective in decreasing the signs of DIC if
      high doses are administered, but effects on survival or other clinically
      significant parameters are at best uncertain. If AT III supplementation is used,
      the dosage should be selected to achieve normal or supranormal plasma levels of
      100% or higher. Results of studies on protein C concentrate, thrombomodulin or
      inhibitors of tissue factor are promising, but the efficacy and safety of these
      novel strategies remains to be established in appropriate clinical trials.

PMID- 9617593
TI  - Practical considerations when treating children with antimicrobials in the
      outpatient setting.
AB  - Over the past decade new antimicrobial agents have been introduced used to treat
      common paediatric infectious diseases such as acute otitis media and sinusitis.
      These agents vary with respect to their mechanism of action, dosage and duration
      of therapy, cost, taste and type of adverse effects. More recently, there has
      been concern about the overuse of antibiotics and increasing bacterial
      resistance, particularly Streptococcus pneumoniae, to these agents. Dosage and
      duration of therapy, cost, taste, and adverse effects play important roles in
      determining success or failure of antimicrobial medications in paediatric
      patients. Use of potential alternatives and adjuncts to antimicrobial treatment,
      such as vaccination, control of environmental risk factors, surgical techniques
      and alternative medical therapies may also be employed, and the practitioner must
      ascertain if their paediatric patients are being treated by any of these methods.
      Rather than listing the therapeutic challenges for all common outpatient
      paediatric infectious diseases, acute otitis media (accounting for over 50% of
      the antimicrobial prescriptions dispensed in childhood) is used to illustrate
      each issue. Clinicians are faced with a growing number of possible antimicrobial
      choices; concomitantly, there is increasing concern that these agents are
      overused. When prescribing antimicrobial agents, we need to be familiar with what
      we can do to optimise the care we provide. By avoiding inappropriate or trivial
      use of antimicrobials, we can preserve and even strengthen our armamentarium
      against disease. Simple strategies can improve compliance with therapeutic
      regimens and improve parental satisfaction.

PMID- 9617594
TI  - Current treatment options for malignant melanoma.
AB  - The incidence of malignant melanoma has increased at an alarming rate over the
      past few decades. Indications are that it will continue to rise in the
      foreseeable future. Primary prevention of malignant melanoma through education of
      the general public regarding the hazards of sun exposure is important in an
      attempt to reduce the incidence of the disease in the future. It can, however, be
      expected to take many years before a decrease in the number of cases of this
      disease is seen. Until such time, the medical oncologist will be faced with an
      increasing number of referrals for both adjuvant therapy and treatment of
      metastatic disease. Many agents have been investigated as possible postsurgical
      adjuvant therapies in patients with malignant melanoma. To date, inteferon-alpha
      (IFN-alpha) given initially intravenously in high doses followed by subcutaneous
      therapy for 1 year, is the only treatment that has been shown to increase disease
      free and overall survival in patients with high-risk melanomas. Patients falling
      into this group should still, wherever possible, be enrolled in prospectively
      randomised clinical trials. Although the prognosis for patients with metastatic
      melanoma remains poor, some progress in the management of this disease has been
      made. It has not yet been conclusively proven that combination chemotherapy
      yields superior results to single agent dacarbazine (DTIC) [which has for many
      years formed the cornerstone of therapy]. Immunotherapy involving IFNs and
      interleukin-2 (IL-2) alone or in combination has yielded similar results to those
      achieved with chemotherapy alone. The combination of chemotherapy plus
      immunotherapy appears to hold promise, with high response rates and often durable
      remissions reported, albeit at the expense of considerable treatment-related
      toxicity. Novel therapies including tumour vaccines and gene therapy also hold
      promise for the future management of this disease.

PMID- 9617595
TI  - Drug therapy alternatives in the treatment of thyroid cancer.
AB  - Therapy of thyroid cancers is based on the removal of the primary disease by
      surgery, replacement of the hormonal deficiencies and subsequent therapy of the
      recurrent and metastatic disease. The metabolic characteristics of many thyroid
      tumors mean that radionuclide techniques have been used in the identification of
      sites of tumour and their subsequent therapy. Differentiated thyroid cancers,
      papillary, follicular and mixed papillary follicular, are treated by surgery-
      usually a total or subtotal thyroidectomy. Postoperatively, patients have
      thyroxine as a replacement therapy and to suppress thyroid-stimulating hormone
      production. Radioiodine therapy is often given to ablate the thyroid remnant.
      This allows (a) adequate follow-up of patients using thyroglobulin measurements
      and assessment scans as necessary, and (b) further therapy with radioiodine for
      metastatic disease. Patients with a short effective half-life of radioiodide may
      require higher activities or pharmacological methods of prolonging the retention
      half-times of iodine. The use of chemotherapy in this group of tumors is limited
      and at best provides palliation. The overall prognosis is good for differentiated
      thyroid cancer; papillary carcinomas have an 80 to 90% 10-year survival, whereas
      follicular tumors are associated with a 65 to 75% 10-year survival. Medullary
      carcinomas may be sporadic or familial, and some of the latter form part of a
      multiple endocrine neoplasia syndrome (MEN). Primary treatment is surgery, and
      total thyroidectomy is usually recommended since tumours are often multifocal.
      The use of radiolabelled metaiodobenzylguanidine (MIBG) and 111In octreotide as
      potential therapeutic agents has been explored and may be potentially useful in
      palliative care. Chemotherapy is of limited benefit. The 10-year survival for
      medullary carcinomas is 60 to 70%. Anaplastic tumours of the thyroid are usually
      aggressive, with a high mortality. Treatment is palliative by surgical debulking;
      some patients may benefit from local radiotherapy or occasionally chemotherapy.
      The use of therapeutic doses of radionuclides is well tolerated, although it may
      be associated with a variety of mostly transient adverse effects, including
      gastritis, thyroiditis and sialadenitis. Therapy with high activities of
      radioiodine require radiation protection precautions. Despite retreatment with
      radioiodine there appear to be no long term effects on the fertility of patients,
      and healthy children are born to women receiving this treatment. 131I remains
      perhaps the most specific cancer therapy available today and has few adverse
      effects. It is difficult to see any marked improvement being developed for
      differentiated thyroid cancer, with the possible exception of targeted gene
      therapy.

PMID- 9617596
TI  - Tolterodine.
AB  - Tolterodine is a competitive muscarinic receptor antagonist which has recently
      been launched for the treatment of overactive bladder. Tolterodine shows
      functional selectivity for the bladder over the salivary glands in vivo, which is
      not attributable to muscarinic receptor subtype selectivity. It is as potent as
      oxybutynin in inhibiting bladder contraction, but is much less potent in
      inhibiting salivation, suggesting that it may have less propensity to cause dry
      mouth in clinical use. In patients with overactive bladder, toleterodine
      significantly reduces the frequency of micturition and number of incontinence
      episodes, while increasing the average volume voided. The onset of
      pharmacological action of tolterodine is < 1 hour and therapeutic efficacy is
      maintained during long term treatment. In comparative trials, tolterodine and
      oxybutynin are equivalent in terms of efficacy. However, tolterodine is
      significantly better tolerated than oxybutynin, particularly with respect to the
      incidence and severity of dry mouth. No clinically relevant ECG changes have been
      noted with tolterodine.

PMID- 9617597
TI  - Triflusal.
AB  - Triflusal is an antiplatelet agent structurally related to the salicylate group
      of compounds, but it is not derived from aspirin (acetylsalicylic acid). Platelet
      antiaggregant properties of triflusal and its active 3-hydroxy-4-trifluoro
      methylbenzoic acid metabolite are primarily mediated by specific inhibition of
      platelet arachidonic acid metabolism. Triflusal, compared with placebo for 6
      months, significantly reduced the incidence of nonfatal myocardial infarction in
      patients with unstable angina. In patients with peripheral arteriopathy, total
      and pain free walking distances were markedly improved in triflusal compared with
      placebo recipients. The cumulative event rate for stroke, ischemic cardiopathy
      and vascular death was lower, but not significantly different, in patients with
      atherothrombotic stroke who received triflusal than in aspirin recipients.
      Differences were significant, and favoured triflusal, in a subgroup of patients
      with > 70% carotid stenosis. Prophylaxis with triflusal for 6 months after
      aortocoronary vein grafting reduced the number of new distal anastomosis
      occlusions and the graft attrition rate more than aspirin or placebo. The
      incidence of deep vein thrombosis or pulmonary embolism in more than 500 patients
      undergoing hip surgery was similar for these 3 treatments. The amount of blood
      transfused was significantly reduced in triflusal compared with aspirin
      recipients who underwent hip surgery. Risk of haemorrhage was also reduced in
      ischemic stroke patients receiving triflusal versus aspirin.

PMID- 9617598
TI  - Amprenavir.
AB  - Amprenavir is a viral protease inhibitor with specificity for the HIV protease
      enzyme. The resistance profile of amprenavir appears to differ from that of other
      protease inhibitors such as saquinavir and indinavir. Twelve hours after single
      dose administration of amprenavir 1200mg to HIV-infected individuals, the mean
      plasma concentration of the drug was more than 10-fold greater than the 50%
      inhibitory concentration for HIV-1IIIB in peripheral blood lymphocytes. In a
      small nonblind study, amprenavir monotherapy increased CD4+ cell count and
      decreased viral load in 37 patients with HIV infection and no previous exposure
      to protease inhibitor therapy. Combination therapy comprising amprenavir and
      other antiretroviral agents (abacavir, zidovudine, lamivudine, indinavir,
      saquinavir or nelfinavir) decreased viral load and increased CD4+ cell counts in
      patients with HIV infection. Antiviral efficacy was maintained during up to 24
      weeks' follow-up. Available data suggest that rash, headache and diarrhoea or
      loose stools are the most frequent adverse events associated with amprenavir
      therapy.

PMID- 9617599
TI  - Moexipril. A review of its use in the management of essential hypertension.
AB  - Moexipril is a prodrug which is hydrolysed after oral administration to its
      active metabolite moexiprilat, an inhibitor of the angiotensin converting enzyme
      (ACE). Once daily administration of moexipril 7.5 or 15 mg effectively reduces
      blood pressure in patients with essential hypertension (including the elderly and
      postmenopausal women with this condition). In double-blind randomised comparative
      studies, moexipril 7.5 to 15 mg once daily showed similar efficacy to other
      antihypertensive agents, including captopril, hydrochlorothiazide, atenolol,
      metoprolol, sustained release verapamil and nitrendipine. Combined therapy with
      hydrochlorothiazide and moexipril had a significantly greater antihypertensive
      effect than either agent alone. Moexipril is well tolerated by the majority of
      patients and compares well in this respect with other antihypertensive agents.
      Its tolerability profile appears to be characteristic of ACE inhibitors as a
      class (the most common adverse events being headache, symptoms of upper
      respiratory tract infection and cough). Moexipril generally had no clinically
      significant effect on lipid, glucose or electrolyte metabolism or haematological
      parameters, and, in particular, it was not associated with any significant
      changes in lipid or glucose metabolism in postmenopausal women (with or without
      hormone replacement therapy). CONCLUSIONS: Once daily moexipril is a useful agent
      for the treatment of essential hypertension, which compares well with currently
      available options in terms of clinical efficacy and tolerability. In addition,
      clinical experience to date supports its use in postmenopausal women.

PMID- 9617602
TI  - Female breast masses during childhood: a 25-year review.
AB  - Thirty females were treated at our unit with the diagnosis of breast mass between
      1970 and 1995. Twenty-seven girls had surgical intervention; for fibroadenoma (n
      = 14), cystosarcoma phylloides (n = 5), fibrocystic disease (n = 4), intraductal
      papilloma (n = 2), metastatic carcinoma (n = 1) and fat necrosis (n = 1), while
      three patients with fibroadenoma were managed nonoperatively. Surgical
      complications included a nipple slough and hematoma requiring surgical drainage
      in two patients after the excision of giant fibroadenomas. Our experience
      revealed that most of the breast masses can be handled operatively through a
      circumareolar incision without any major complications. Protection of the
      developing breast bud, nipple and areola is as important as the appropriate
      excision of the lesion. A detailed physical examination accompanied with
      ultrasound scan is sufficient for the correct diagnosis in most cases. Female
      adolescents presenting with fibroadenoma, fibrocystic disease and cystosarcoma
      phylloides should undergo surgery after a reasonable observation period of 3-4
      menstrual cycles. Excision of discrete, undiagnosed breast masses is warranted.
      This is indicated first to define the pathology and rule out the rare malignancy,
      second to obviate enlargement and asymmetry, and third to allay the apprehension
      of the child and family.

PMID- 9617603
TI  - A critique of systemic steroids in the management of caustic esophageal burns in
      children.
AB  - Five hundred and nineteen NaOH ingestion cases were admitted to our department
      between 1975 and 1994, and examined via esophagoscopy in the first 48 hours. Two
      hundred and forty-six patients in this series were diagnosed as severe burns
      endoscopically. This group of 246 patients were evaluated in a retrospective
      study to determine whether systemic steroid treatment had any place in preventing
      stricture formation following severe esophageal burns. Seventy-nine patients in
      this group were divided into three subgroups and they received methyl
      prednisolone parenterally in three different regimens. The control group
      consisted of 167 patients admitted between the years 1986 and 1994 who did not
      receive any form of steroid treatment. There were no statistically significant
      differences between the healing rates of the subgroups and the control group (p >
      0.01). The authors concluded that systemic steroid treatment has no beneficial
      effect on esophageal wound healing following caustic esophageal burns.

PMID- 9617600
TI  - Levonorgestrel subdermal implants. A review of contraceptive efficacy and
      acceptability.
AB  - Levonorgestrel 6-capsule subdermal implants (Norplant) are an effective form of
      reversible contraception. When implanted under the skin of the upper arm, they
      release drug into the circulation at a relatively constant rate over 5 years.
      Generally, the cumulative pregnancy rate at the end of 5 years' levonorgestrel
      implant use is less than 2 per 100 users. The implants provide contraceptive
      efficacy equivalent to, or better than, that provided by other reversible methods
      (including oral contraceptives). Younger women are more likely than older women
      to become pregnant while using levonorgestrel implants. Bodyweight was positively
      correlated with risk of pregnancy in a number of studies, but may not be a factor
      with the currently available 6-capsule implant formulation. Limited data suggest
      that a new 2-rod levonorgestrel subdermal system (Jadelle) is as effective as the
      more extensively studied 6-capsule system and has a similar tolerability profile.
      Fertility returns rapidly after the implants are removed. Use of levonorgestrel
      subdermal implants is compatible with breast-feeding. In several studies,
      discontinuation rates were 2 to 15% during the first year of use; cumulative 5
      year discontinuation rates ranged from 22 to 64 per 100 women. Despite a
      substantial incidence of adverse events during therapy, levels of user
      satisfaction are generally high. Menstrual abnormalities (increased or decreased
      menstrual flow, spotting, irregularity and amenorrhoea) affect most women at some
      time during therapy and are the most frequent reason for discontinuing
      levonorgestrel implants before the end of 5 years' treatment (incidence of 4.2 to
      30.7 per 100 users). Mood changes and headache also may lead to discontinuation.
      Other reported adverse events include skin reactions (including acne), dizziness
      and weight gain. Serious adverse events (such as stroke, thrombotic
      thrombocytopenia and idiopathic intracranial hypertension) have been reported
      during levonorgestrel implants therapy, but the population incidence is difficult
      to calculate and causality is unclear. According to 3 pharmacoeconomic analyses
      from an institutional or managedcare perspective, all contraceptive interventions
      result in net cost savings. It is not clear whether levonorgestrel implants
      provide greater or smaller economic benefits than combined oral contraceptives.
      CONCLUSION: Levonorgestrel subdermal implants provide effective long term
      contraception. Despite a high incidence of menstrual adverse events, overall
      levels of user satisfaction are high, and 1-year continuation rates are better
      than those for combined oral contraceptives. Levonorgestrel subdermal implants
      are a good choice of contraceptive method in women who desire effective
      contraception, but who are unable to, or prefer not to, comply with an oral
      regimen.

PMID- 9617604
TI  - Modified Toupet wrap for gastroesophageal reflux in childhood.
AB  - It was the aim of our study to follow up our clientele of infants and children
      who had undergone a partial (posterior) Toupet wrap or modified Toupet wrap.
      METHODS: All 22 children who had undergone a posterior partial wrap within a 4
      year period were followed up for 4.0 years (0.6-5.7 years). 36.4% of children had
      associated anomalies such as operated esophageal atresia, operated congenital
      diaphragmatic hernia, Gregg's syndrome or arthrogryposis multiplex congenita. 14%
      of children suffered from some form of neurological impairment. Prior to
      operation the 4 main examinations for detection and documentation of
      gastroesophageal reflux (GER) disease were carried out where possible. Five
      children underwent Toupet fundoplication and in 17 children a modified Toupet
      fundoplication with reinforcement of the wrap fixation using a Vicryl-mesh was
      applied. A pH-metric study and upper gastrointestinal series with reflux testing
      were done in all 22 children at least 6 months postoperatively. Successful
      control of GER was documented in 21 of 22 children (95.5%). In the remaining
      child a reoperation was necessary to correct recurrence of a sliding hiatal
      hernia and GER. In three children (13.6%) postoperative complications occurred
      within the first 2 weeks following fundoplication and were managed medically.
      Following the postoperative 24-hour pH-metric study and the upper
      gastrointestinal series with reflux testing, one child with normal results at
      these investigations was lost to follow-up. The remaining 21 children were
      followed up for another 10 months to 5 years. Four children (18.2%) were found to
      suffer from functional complications (mild dumping syndrome, retrosternal pain,
      vomiting during episodes of asthma, dysphagia). No gas bloat syndrome occurred
      within the follow-up interval and all children were able to belch and vomit.
      There was no mortality in our limited series. Our series indicates that the
      partial (posterior) Toupet wrap and the modified Toupet fundoplication are safe
      and effective procedures for surgical correction of GER in children which
      preserve the ability of infants and children to belch and vomit.

PMID- 9617601
TI  - Sumatriptan. An updated review of its use in migraine.
AB  - Sumatriptan is a selective agonist at serotonin 5-HT1-like receptors, including 5
      HT1B/1D subtypes. It is an effective treatment for acute migraine attacks and the
      injectable form has also shown efficacy in the treatment of cluster headaches. In
      placebo-controlled clinical trials, sumatriptan, administered subcutaneously,
      orally, intranasally or rectally was significantly more effective than placebo in
      relieving migraine headache and in producing resolution or reduction of other
      symptoms associated with migraine, including nausea, photophobia and phonophobia.
      Improvements in clinical disability were also significantly greater after
      sumatriptan than after placebo. Headache recurred in 21 to 57% of patients who
      received oral or subcutaneous sumatriptan, but most patients responded to a
      second dose of the drug. Results of comparative trials showed that subcutaneous
      sumatriptan 6 mg was significantly more effective than either patients' usual
      antimigraine treatments or intranasal dihydroergotamine mesylate 1 mg in
      relieving migraine headache. Subcutaneous sumatriptan 6 mg and subcutaneous
      dihydroergotamine mesylate 1 mg provided similarly effective migraine relief, but
      the headache recurrence rate was significantly higher after sumatriptan than
      after this formulation of dihydroergotamine mesylate. Response rates achieved
      after oral sumatriptan were similar to those reported after treatment with oral
      naratriptan, rizatriptan or lysine acetylsalicylate plus metoclopramide.
      Treatment of acute migraine attacks with oral or subcutaneous sumatriptan leads
      to less loss of workplace productivity than other antimigraine therapies. Several
      pharmacoeconomic analyses showed that gains in workplace productivity in
      sumatriptan recipients ranged from 12.1 to 89.8 hours per patient per year.
      Significant improvements from baseline in overall health-related quality-of-life
      scores were also experienced by sumatriptan recipients. Sumatriptan is generally
      well tolerated. Nausea, vomiting, malaise and fatigue are the most common adverse
      events with oral sumatriptan. Injection site reactions occur in 10 to 40% of
      patients receiving the drug subcutaneously. A bitter taste at the back of the
      mouth occurs frequently after intranasal administration. Serious adverse events
      occur in about 0.14% of patients with migraine treated with sumatriptan. As the
      drug is associated with the rare development of cardiovascular effects, it is
      contraindicated in patients with a history of cardiovascular disease.
      CONCLUSIONS: Despite its relatively high acquisition cost, reductions in lost
      workplace productivity experienced by patients treated with sumatriptan may
      result in savings in the overall cost of migraine to society. Thus, sumatriptan
      is a useful first- or second-line treatment option for patients with moderate or
      severe migraine.

PMID- 9617605
TI  - Surface umbilical pyloromyotomy.
AB  - BACKGROUND: Despite much initial enthusiasm, umbilical pyloromyotomy has failed
      to achieve widespread popularity. This mostly relates to difficulty with
      delivering the pyloric tumour through the relatively small incision. METHOD: A
      new technique for umbilical pyloromyotomy is described in which a circumumbilical
      skin incision with a right lateral extension is combined with transverse division
      of the linea alba and part of the right rectus muscle. The pyloric tumour is
      easily delivered to the skin surface through this generous minilaparotomy. After
      muscle closure the lateral skin extension is swung medially as described and
      incorporated within the umbilical scar. RESULTS: We report our experience of 30
      cases in which this technique was successfully employed. The pyloromyotomy was
      done on the surface in all cases and the resulting scar was barely visible in the
      folds of the umbilicus.

PMID- 9617606
TI  - Rarity of surgical complications after postchemotherapy nephrectomy for
      nephroblastoma. Experience of the International Society of Paediatric Oncology
      Trial and Study "SIOP-9". International Society of Paediatric Oncology
      Nephroblastoma Trial and Study Committee.
AB  - The aim of the study was to assess rates and types of nephrectomy-related
      complications in children nephrectomized for nephroblastoma after preoperative
      chemotherapy. Records of 598 Wilms' tumour patients registered in the
      International Society of Paediatric Oncology Trial & Study No. 9 (SIOP-9), and
      pretreated correctly according to the protocol with vincristine + actinomycin D
      +/- epirubicine or adriamycin prior to nephrectomy, were retrospectively
      reviewed. Forty-nine patients (8%), who suffered from 54 complications, were
      identified. Most frequent events were small-bowel occlusions (3.7%) and tumour
      ruptures (2.8%). Other complications were registered in 2.0% of cases. The low
      rate of nephrectomy complications and no deaths related to registered ones, are
      another argument for preoperative chemotherapy in Wilms' tumour patients.

PMID- 9617607
TI  - Morphologic alterations of the enteric nervous system and deficiency of non
      adrenergic non-cholinergic inhibitory innervation in neonatal necrotizing
      enterocolitis.
AB  - Although damage to intramural nervous tissue should be expected in neonatal
      necrotizing enterocolitis (NNEC), as the pathology of NNEC is defined by
      substantial destruction of the bowel wall, only a few studies have considered its
      implication. Thus, the aim of the study has been to examine morphological
      alterations of the enteric nervous system (ENS) in intestinal segments affected
      by NNEC. Immunohistochemical methods allowed the demonstration of both neuronal
      and glial elements and the assessment of an altered localization of non
      adrenergic non-cholinergic (NANC) inhibitory mediators within the intramural
      plexuses. Intestinal segments from patients with NNEC (n = 8) and control
      subjects (n = 3) were obtained and submitted to immunohistochemical examination
      incubating with antibodies against protein gene product (PGP) 9.5, protein S-100,
      vasoactive intestinal polypeptide (VIP) and nitric oxide synthase (NOS). The most
      severe damage of nervous tissue was found within the plexus mucosus and plexus
      submucosus internus. The ganglionated plexuses showed a loss ot both glial and
      nerve cells with various stages of cell deterioration and the formation of
      central lesions within the myenteric ganglia. The observed neuropathologic
      changes correspond to the group of acquired segmental hypoganglionosis. Specimens
      from patients with NNEC were also characterized by an absence of immunoreactive
      VIP and NOS in the plexus submucosus and within the circular muscle layer. The
      deficiency in NANC inhibitory innervation may contribute to the formation of
      functional obstructions following acute NNEC. Furthermore, it is likely that the
      neuropathological lesions induced in early stages of NNEC may result in
      dysfunctional intestinal motility facilitating intraluminal bacterial overgrowth
      and translocation, and therefore, possibly promote the self-perpetuating
      pathophysiologic cycle culminating in progressive NNEC. As an additional finding,
      two patients with NNEC showed typical features of intestinal neuronal dysplasia
      (IND). The association of NNEC and IND is reviewed in the literature and possible
      causalties are discussed.

PMID- 9617608
TI  - Neurovesical dysfunction in patients with anorectal malformations.
AB  - The aim of the study is to investigate the incidence of neurovesical dysfunction
      (NVD) in patients with operated anorectal malformations (ARM) and its
      relationship with sacral abnormalities. Between September 1992 and April 1994
      cystomictiometric and electromyography investigations were performed for 33
      patients operated on for anal atresia. The age of these 14 male and 19 female
      patients ranged between 1-17 years (mean age: 7.7). The level of ARM was
      supralevator in 10 patients and infralevator in 23 patients. The x-ray of 14
      patients showed lumbosacral abnormalities. In urodynamic investigation, NVD was
      observed in 15 patients (45.4%). 4 of the patients had signs developed secondary
      to organic subvesical obstruction. The urodynamic results of 14 patients were in
      the normal range. NVD rate was found to be 70% in patients with supralevator anal
      atresia, 34.7% in patients with infralevator anal atresia, 64.2% in patients with
      sacral abnormalities and 31.5% in patients with no sacral abnormality.
      CONCLUSION: NVD incidence increased in patients with supralevator ARM and in
      patients with sacral abnormalities. However, presence of infralevator abnormality
      or absence of sacral abnormality does not eliminate NVD. We think that, whenever
      NVD is suspected in a patient with ARM, urodynamic investigations should be
      performed as a routine investigation of the urinary tract.

PMID- 9617609
TI  - Modified-Mathieu's technique: a variation of the classic procedure for
      hypospadias surgical repair.
AB  - Distal penile curvature associated with anterior hypospadias can be corrected by
      urethral plate mobilization. The authors present 11 cases, in which this
      procedure was performed modifying the classic Mathieu's technique in the surgical
      treatment of coronal and distal shaft hypospadias associated with chordee.
      Performing this modified-Mathieu's technique, excellent results, both functional
      and cosmetic, are obtained without any complication.

PMID- 9617610
TI  - Jeune's asphyxiating thoracic dystrophy of the newborn.
AB  - A 13-month-old patient with Jeune's thoracic asphyxiating dystrophy, was
      surgically treated using a methyl-methacrylate (acrylic) prosthesis. Although
      postoperative recovery was fast, the patient died of respiratory distress two
      months following surgery. Limitations of currently available surgical techniques
      and the need for long-term results will be discussed.

PMID- 9617611
TI  - Tubular esophageal duplication associated with esophageal stenosis, pericardial
      aplasia, diaphragmatic hernia, ramification anomaly of lower lobe bronchus and
      partial pancreas anulare.
AB  - Alimentary tract duplications are rare anomalies, which are often associated with
      other congenital malformations. We report on a newborn with the combination of
      tubular esophageal duplication, congenital esophageal stenosis, ramification
      anomaly of lower left lobe bronchus, complete pericardial aplasia and malrotation
      of the bowel with a partial pancreas anulare. The diagnoses are based on
      esophagogram, bronchogram, bronchoscopy, gastroscopy, explorative thoracotomy and
      laparotomy. The treatment was a resection of the duplication per thoracotomy,
      esophageal myotomy with fundoplicatio.

PMID- 9617612
TI  - Gastroschisis and total intestinal atresia.
AB  - Gastroschisis is an uncommon condition which is now being detected at an earlier
      stage due to the use of routine antenatal ultrasound scanning. The presence of
      intestinal atresia secondary to impairment of the vascular supply is well
      recognised and is associated with a poorer outcome because of the potential for
      loss of bowel length. We report a case of gastroschisis in which there was
      resorption of the bowel and closure of the abdominal wall defect. At laparotomy
      there was total intestinal atresia.

PMID- 9617613
TI  - Mesenteric fibromatosis.
AB  - Two rare cases of mesenteric fibromatosis are presented. The first patient had a
      right upper quadrant mass and colicky abdominal pain. The tumor originated from
      the mesentery of the colon and it infiltrated the gallbladder, cystic duct, and
      the liver. The second patient had severe hematemesis and melena. The origin of
      the tumor, which infiltrated 3/4 part of the stomach, the gastrohepatic ligament,
      the first part of the duodenum, and the liver could not be determined. In the
      first patient, partial colectomy and cholecystectomy were performed and the liver
      lesion was completely excised. The second patient underwent subtotal gastrectomy
      and left lobectomy of the liver. The first part of the duodenum was excised.
      Gastrojejunostomy was performed. No recurrence was recorded in either patients
      during 16 and 13 months follow-up, respectively. In this report, diagnostic aids,
      differential diagnosis and treatment of this rare disease are discussed.

PMID- 9617614
TI  - Rectal drainage: unusual evolution of a psoas abscess.
AB  - We report two cases of primary psoas abscess in two patients of 15 months and 4
      years of age. As the first case showed the natural history of this process the
      second one was large enough to produce a huge ureterohydronephrosis and to drain
      through the rectal wall to the rectum spontaneously, although this natural way
      did not achieve complete drainage. Both were treated by open drainage and
      systemic antibiotics with good response. They were discharged at the 7th and 12th
      postoperative day. 5 months later no complication has come up. Etiological,
      clinical and therapeutic aspects of this unusual pathology are reviewed.

PMID- 9617615
TI  - Concepts and considerations for repair of a severe cloacal anomaly.
AB  - A 1.8 kg chromosomally normal child was suspected antenatally to have a cloacal
      anomaly and oligohydramnios. Both parents had a chromosome 9 inversion (inv [9]
      [p11 q13]). Postnatal study showed a high confluence of the urinary, genital and
      intestinal tracts. Because of prematurity, a right colostomy was performed on a
      short colon, but the genitourinary tract was not drained. Poor weight gain,
      urinary tract infection and septicaemia led to a one-stage reconstruction at 5
      months of age and a weight of 3.2 kg. Follow-up although short at 15 months, is
      encouragingly suggestive of urinary and faecal continence. The vagina is patent.
      This paper considers concepts in cloacal management and submits for evaluation an
      alternative surgical plan to the presently almost exclusively accepted posterior
      sagittal approach of Pena and De Vries.

PMID- 9617616
TI  - Surgical management of uterine prolapse in an infant.
AB  - Neonatal uterine prolapse has been rarely described in the literature. Most cases
      have an underlying cause, usually spinal cord malformations. Conservative
      treatment has been advocated for this condition in the neonates. We would like to
      present the late presentation of a child with complete uterine prolapse which was
      treated with classical uterine ventrisuspension.

PMID- 9617617
TI  - Molecular forms of serum prostate-specific antigen: the clinical usefulness of
      percent free PSA to discriminate prostate cancer from BPH.
AB  - The development of increasingly specific diagnostic assays has allowed the
      detection of various forms of prostate-specific antigen (PSA). It has been found
      that the proportion of free to total PSA (percent free PSA) is significantly
      lower in men with prostate cancer than in those with other benign diseases. In
      order to distinguish early, curable prostate cancer from benign prostatic
      hyperplasia (BPH), percent free PSA measurement is most useful when the total PSA
      value is 3-10 ng/ml. The measurement of the proportions of these different forms
      of PSA, i.e., percent free PSA, may constitute an important diagnostic tool, able
      to differentiate between benign and malignant prostatic disease with increased
      specificity, reducing false-positive results and, therefore, improve patient
      prognosis.

PMID- 9617618
TI  - [The relationship between the production of interleukin-6 and the proliferating
      cell nuclear antigen (PCNA) expression in renal cell carcinoma].
AB  - The relationship between the proliferating cell nuclear antigen (PCNA) expression
      in renal cell carcinoma (RCC) determined by immunohistochemical staining using
      the PC10 clone, and the preoperative serum interleukin-6 (IL-6) value determined
      by ELISA was examined. The secretion of IL-6 in RCC was also examined
      immunohistochemically using an anti-IL-6 antibody. The PCNA labeling rate was
      significantly higher in grade 3 tumors than in grade 1 tumors (p < 0.05), but
      there were no significant differences between the other grades or TNM stages. No
      significant correlation was obtained between the serum level of IL-6 or the
      positive cell rate of IL-6 and the pathological grade of the RCC. A correlation
      was observed between the PCNA labeling rate and positive cell rate, and between
      the serum IL-6 value and CRP or ESR. In conclusion, the secretion of IL-6 was
      detected in RCC tissue, and was suggested to be a tumor factor responsible for
      the growth and spread of RCC. The serum IL-6 value is considered to reflect the
      total secretion of IL-6 produced by the RCC and accessory cells, i.e., monocyte
      macrophage lineage cells, endothelial cells and fibroblasts.

PMID- 9617619
TI  - [Experience in ESWL monotherapy using Lithostar--comparative study on the
      efficacy of standard-tube with C-tube].
AB  - Between October 1990 and April 1996, we treated 892 upper urinary tract stones
      with ESWL therapy using Lithostar (Siemens Medizinische Technik, Erlangen,
      Germany). In March 1993, the coupling head of lithotriptor was upgraded from
      "standard-tube" to "C-tube". The C-tube has approximately two times or more
      destructive energy and intensity than the standard-tube. In this study, we
      analyzed the clinical results according to type of coupling head in 713 cases
      treated by ESWL monotherapy and evaluated 3 months after the initial treatment.
      The overall success rate at 3 months after ESWL was 85% in the standard-tube
      cases and 93% in the C-tube cases; the stone-free rate was 72% and 82%,
      respectively. There were no cases in which had to be discontinued due to ESWL
      severe side effects. However, in 66.1% of the C-tube cases and 31.1% of the
      standard-tube cases, a sufficient destructive intensity could not be used because
      of pain. Within a group that received sufficient destructive intensity, the C
      tube was able to reduce both duration of the procedure and the number of shots to
      two thirds of that of the standard-tube.

PMID- 9617620
TI  - [14C-oxalate autoradiographic studies on distribution of oxalate and calcium
      oxalate crystal fixation in rat kidney].
AB  - To elucidate the intrarenal distribution of oxalate and to reveal the first site
      of calcium oxalate crystal fixation along the nephron, we carried out 14C-oxalate
      renal microautoradiography by the thaw mount method 30, 60 and 90 min after
      intravenous administration of 14C-oxalate, in normal rats and in hyperoxaluric
      rats fed a vitamin B6-deficient diet for 4 and 9 weeks. In normal rats,
      radioactivity was observed in the entire kidney area at 30 min after the
      injection and at 90 min there was radioactivity only in the papilla, where
      radioactivity appeared in the parenchyma, mamely the epithelial cells of
      collecting ducts and the surrounding interstitial tissue. In hyperoxaluric rats,
      microautoradiograms showed the spotted deposits of 14C-oxalate in both renal
      papilla and medulla. In 600 x magnification of the autoradiograms, most of the
      deposits were detected in the epithelial cells of collecting ducts and the
      surrounding interstitial tissue. These deposits were identified by a polarizing
      microscope and X-ray microanalysis as crystal deposits of calcium oxalate. These
      results indicated that oxalate remained for an extended period of time in the
      epithelial cells of collecting ducts and in the surrounding interstitial tissue
      in renal papilla, and the calcium oxalate crystals fixed to the same tissue was
      the first step in the development of calcium oxalate stones.

PMID- 9617621
TI  - [Intravesical bacillus Calmette-Guerin instillation for patients over 80 years
      old].
AB  - To study the efficacy and the safety of intravesical bacillus Calmette-Guerin
      (BCG) therapy for very elderly patients with superficial bladder cancer, we
      retrospectively compared patients over 80 years old who had received BCG therapy
      at our department between 1991 and 1996 (Group A; 10 patients 11 courses), with
      those below 80 years old (Group B, 17 patients 18 courses). In these patients,
      skin test reactivity to purified protein derivative showed a significant negative
      correlation with age (p = 0.016). No irreversible complications were observed in
      any patient. Persistence of acid-fast bacilli for more than one month after the
      termination of the course was observed in two patients in group A, and one in
      group B. A comparison of the cases undergoing eradicational BCG therapy in the
      two groups, grade 2 transitional cell carcinoma (TCC) was significantly more
      predominant than grade 3 TCC in group A (p = 0.004). (None of the tumors in group
      A were of grade 3) The disease-free rate was significantly lower in group A (p <
      0.05), but 5 of the 10 patients in this group were finally disease-free. From
      these results, we conclude that intravesical BCG instillation therapy can be
      performed in patients over 80 years old, although a relatively lower disease-free
      rate is expected and special attention should be taken with regard to persistent
      BCG infection. The lower disease-free rate could be attributable to either
      diminished cellular immunity or a difference in tumor grade, although a definite
      conclusion could not be obtained here.

PMID- 9617622
TI  - [Prognostic significance of clinical stage including extent of disease (EOD) in
      prostate cancer].
AB  - We analyzed the prognostic significance of clinical stage using extent of disease
      (EOD) grading system in 288 patients with prostate cancer between 1970 and 1994.
      The cause-specific survival rate for EOD4 was significantly lower (p < 0.01) than
      that for the other EOD categories. On the other hand, the cause-specific survival
      rate for EOD1 was significantly higher (p < 0.01) than that of the other EOD
      categories, and moreover, it was similar to the cause-specific survival rates for
      stage C and D1. The cause-specific survival rate of EOD1 and poorly
      differentiated cases was higher than that of EOD2 or 3 and well or moderately
      differentiated cases until 2 years after treatment, but after 3 years, the cause
      specific survival rate for EOD1 and poorly differentiated cases was lower than
      that for EOD2 or 3 and well or moderately differentiated cases. These findings
      suggest that the volume of cancer is associated with the prognosis of prostate
      cancer that failed in radical treatment and that in stage D2, histological grade
      is more closely associated with the prognosis after treatment for 3 years.

PMID- 9617624
TI  - [A case of solitary retroperitoneal neurofibroma].
AB  - A 70-year-old woman was admitted to our hospital complaining of epigastralgia.
      Computed tomography, ultrasonography and magnetic resonance imaging revealed a
      round tumor measuring 6 cm in diameter, which was located in the medial side of
      the right kidney. It was successfully removed without injury to the surrounding
      large vessels and organs. Histological diagnosis was benign neurofibroma. This is
      the 27th case of solitary retroperitoneal neurofibroma reported in Japan.

PMID- 9617623
TI  - [Clinical study on poor-risk patients with non-seminomatous germ cell tumor].
AB  - Between 1988 and 1996, we treated 11 poor-risk patients with non-seminomatous
      germ cell tumors (NSGCT) at Nagoya University Hospital. "Poor-risk" was defined
      as i) advanced disease equal to or greater than class 7 of the Indiana University
      Classification (7 patients), ii) primary mediastinal extragonadal NSGCT (2), iii)
      tumor markers not normalized by the induction chemotherapy (1) or iv) primary
      retroperitoneal NSGCT with multiple lung metastases (1). Two patients with
      mediastinal tumors died during the chemotherapy. The minimal volume of fluid must
      be administered to patients with giant mediastinal tumors. The tumor marker
      normalized during the induction chemotherapy in only three patients. Three
      patients, whose tumor markers elevated during or one month after the induction
      chemotherapy, eventually died of cancer. The tumor markers in five of the seven
      patients which had not normalized during the induction chemotherapy, had
      decreased to the normal range during the salvage chemotherapy and two of the five
      subsequently achieved the status of "no evidence of disease" (NED). Six patients
      with and two without normalized tumor markers underwent retroperitoneal lymph
      nodes dissection and/or resection of residual tumors. Pathological examination of
      the resected tumors showed necrosis/fibrosis in five patients and two had
      elevated tumor markers immediately after the surgery and eventually died of the
      disease. Overall, eight (73%) of 11 poor-risk patients achieved a complete
      response but only five (45%) eventually achieved a NED status that was maintained
      (6.6 +/- 3.0 years). Our results were not satisfactory, and we believe that new
      strategies, such as early high-dose chemotherapy, are required for poor-risk
      patients, who are not likely to respond well to the induction chemotherapy.

PMID- 9617625
TI  - [Bilateral renal vein thrombosis extending into the inferior vena cava associated
      with nephrotic syndrome: a case report].
AB  - We present a case of bilateral renal vein thrombosis extending into the inferior
      vena cava associated with nephrotic syndrome. A 55-year-old Japanese woman who
      had complained of severe median lumbago for 4 months was referred to our
      department because of bilateral renal vein thrombosis extending into the inferior
      vena cava demonstrated on CT. Investigations confirmed the diagnosis of nephrotic
      syndrome. Although treatments using interventional radiology had been planned,
      she died suddenly probably owing to pulmonary embolism before the commencement of
      the treatments.

PMID- 9617626
TI  - [Primary carcinoma in situ of the ureter: a case report].
AB  - A 55-year-old male visited our hospital with a complaint of gross hematuria and
      right lower abdominal pain. Cytological findings of voided urine suggested the
      presence of malignant cells. Cystoscopic examination revealed bloody urine
      discharge from the right ureteral orifice and no abnormality in the bladder wall.
      The retrograde pyelogram showed no tumor masses. However, malignant cells were
      detected cytologically in the right ureteral catheteral urine twice. Under the
      preoperative diagnosis of primary urothelial tumor of the right upper urinary
      tract, right total nephroureterectomy was performed. A histological study
      revealed transitional cell carcinoma in situ in the lower portion of the ureter.
      We reviewed 46 cases of primary carcinoma in situ of the upper urinary tract
      previously reported in Japan.

PMID- 9617627
TI  - [Two cases of delayed ureteral fistulas following rectal amputation].
AB  - We report two rare cases of delayed ureteral fistulas which occurred one month
      following rectal amputation. Case 1 was a 52-year-old male who underwent
      abdominal perineal resection of the rectum. One month after surgery, the patient
      had a paralytic ileus. Computed tomographic (CT) scan and drip infusion
      pyelography showed left ureteral fistula and a large pelvic urinoma. Because
      retrograde placement of a double-J stent was unsuccessful, antegrade placement of
      the double-J stent was performed. The fistula and urinoma healed soon after the
      placement of the double J stent. Case 2 was a 43-year-old male who underwent
      abdominal sacral resection of the rectum. One month after surgery, a large amount
      of urine began to drain from the perineal wound. CT scan and retrograde
      pyelography showed a right ureteral fistula and a large pelvic urinoma. There had
      been temporary improvement in the discharge without the treatment of the ureteral
      fistula, only for it to return more profusely. Because placement of a double-J
      stent was unsuccessful, right percutaneous nephrostomy was performed, after
      which, a right ureterocysto-neostomy (Boari flap method) was performed. We
      advocate the initial use of the double-J stent or percutaneous nephrostomy in
      ureteral fistula. This approach is simple and may cure the fistula. If
      unsuccessful, it will not hinder subsequent open surgery.

PMID- 9617628
TI  - [A case of clear cell adenocarcinoma of the female urethra].
AB  - Clear cell adenocarcinoma of the female urethra is a rare disease. We herein
      report the 23rd case of clear cell adenocarcinoma of the female urethra in Japan.
      A 75-year-old female visited our hospital because of pollakisuria. Pelvic CT
      revealed a 2.2 cm tumor surrounding the entire circumference of the urethra with
      pelvic lymph node metastases. Chest CT revealed mediastinal lymph node
      metastases. She underwent anterior pelvic exenteration and ileal conduit urinary
      diversion. Pathological diagnosis of the tumor was clear cell adenocarcinoma. She
      has been alive 11 months after surgery in spite of enlarged mediastinal lymph
      node metastases.

PMID- 9617629
TI  - [A case of ovarian cyst presenting as urinary retention].
AB  - A 54-year-old woman presented with repeated episodes of urinary retention during
      an approximately 7-month period of dysuria. Computerized tomography scan revealed
      a right ovarian cyst and a small uterine myoma. At operation, the ovarian cyst
      was deeply incarcerated into the pouch of Douglas displacing the bladder neck and
      the uterine cervix in the anterocephalad direction. Histological diagnosis of the
      resected cyst was benign mucinous cystadenoma. This is the 5th reported case of
      urinary retention caused by ovarian cyst in the Japanese literature.

PMID- 9617630
TI  - [Priapism treated by caverno-glandular shunt, caverno-saphenous shunt and caverno
      spongiosum shunt: report of a case].
AB  - A 44-year-old man visited a local urologist complaining of continuous pain and
      tumescence at penis persisting for 3 days. He was diagnosed with priapism. A
      caverno-glandular and caverno-saphenous shunt was performed. He presented to our
      hospital 3 days later, because the symptoms especially tumescence continued. We
      confirmed the diagnosis of low-flow priapism from cavernosography and
      intracavenal blood-gasometry and performed caverno-spongiosum shunt. Detumescence
      was finally achieved after the operation.

PMID- 9617631
TI  - Mouse-specific carcinogens: an assessment of hazard and significance for
      validation of short-term carcinogenicity bioassays in transgenic mice.
AB  - 1. The International Conference on the Harmonisation of Technical Requirements
      for the Registration of Pharmaceuticals for human use (ICH) has agreed that
      bioassay data from only one species, the rat, supported by appropriate
      mutagenicity and pharmacokinetic data and also information from new (unvalidated)
      short term in vivo screening tests for potential carcinogenicity, could be used
      for the licensing of human medicines. This proposal has been supported by reviews
      of the utility of testing pharmaceuticals in the mouse which have concluded that
      the mouse bioassay contributes little to regulatory decisions. The current review
      was undertaken to identify 'genuine' mouse-specific carcinogens using the Gold
      Carcinogenicity Potency Database (CPD) for the initial identification of
      potential mouse-specific carcinogens from published literature. Hazard
      assessments were completed for these chemicals with particular attention focused
      on the 'genuine' mouse-specific carcinogens. The significance of such chemicals
      has been discussed together with consideration of on-going work on the validation
      of short-term carcinogenicity bioassays using transgenic mice. 2. Seventy-six
      potential mouse specific carcinogens were identified through the Gold
      Carcinogenicity Potency Database. Following more detailed consideration a total
      of ten chemicals were excluded from further consideration (three were
      multispecies carcinogens, five were considered to be non-carcinogenic in the
      mouse, and the data for two were uninterpretable). The review focused on the
      remaining 66 chemicals. There was equivocal evidence of carcinogenicity to the
      rat for 28 chemicals and inadequate data for a further 23 chemicals. Fifteen
      'genuine' mouse-specific carcinogens were identified. These 15 chemicals comprise
      two genotoxic mouse-specific carcinogens (N-methylolacrylamide (924-42-5), 2,6
      Dichloro-p-phenylenediamine (609-20-1); five non-genotoxic mouse-specific
      carcinogens 2-Aminobiphenyl.HCl (2185-92-4), Captan (133-06-2), Dieldrin (60-57
      7), Diethylhexyladipate (103-23-1), and Probenicid (57-66-9); five mouse-specific
      carcinogens with equivocal evidence of mutagenicity were identified; (2,4
      diaminophenol.2HCl (137-09-7), Dipyrone (68-89-3), Ozone (10028-15-6), Vinylidene
      chloride (75-35-4), and Zearalenone (17924-92-4)), and three mouse-specific
      carcinogens with inadequate mutagenicity data (Benzaldehyde (100-52-7), Piperonyl
      sulphoxide (120-62-7), Ripazepam (26308-28-1)). 3. It is suggested that the two
      genotoxic mouse carcinogens would have been considered as potential carcinogens
      in the absence of a mouse bioassay. Of the five non-genotoxic mouse-specific
      carcinogens; three induced tumours in mouse liver only and are considered as
      being of low potential hazard to human health. The remaining two chemicals would
      have been missed in the absence of a mouse bioassay (2-aminobiphenyl (2185-92-4)
      and captan (133-06-2)) and thus are good candidates for evaluation in the short
      term bioassays in transgenic mice currently being validated. 4. The hardest group
      of mouse-specific carcinogens to evaluate are those for which there is equivocal
      or inadequate mutagenicity data. The difficulty in evaluating these particular
      chemicals emphasises the need for adequate mutagenicity data in addition to
      adequate carcinogenicity data in order to assess potential hazards to human
      health. Hazard assessments and a consideration of the potential role for short
      term bioassays in transgenic mice for the eight chemicals in this subgroup are
      presented. 5. A number of general conclusions have been derived from this review.
      Firstly, there are insufficient published genotoxicity data to allow a full
      assessment fo mutagenic potential for 57/76 of the potential mouse-specific
      carcinogens identified from the CPD. This is surprising given the clear value of
      such data in interpreting bioassay results and the much greater resources
      required for carcinogenicity bioassays. (ABSTRACT TRUNCATED)

PMID- 9617632
TI  - Extension of the protocol of OECD guideline 407 (28-day repeated dose oral
      toxicity test in the rat) to detect potential immunotoxicity of chemicals.
AB  - To indicate the immunotoxic potential of chemicals the examinations prescribed by
      OECD Guideline 407 were extended by the following additional toxicological,
      haematological, histopathological, and immune function examinations: absolute and
      relative organ weight of spleen, thymus, popliteal lymph nodes, lung and brain;
      histopathology of thymus, mesenteric lymph nodes, popliteal lymph nodes, bone
      marrow (femur), Peyer's patches (ileum), lungs and colon; PFC assay (spleen), T
      cell proliferation and NK cell assay. Two well known immunosuppressants
      Azathioprine (AZA) and Cyclosporine A (CysA) were chosen as model compounds at a
      dose range which do not cause visible toxic signs on the animals during a 28 days
      treatment period. The results show that the applied experimental system is much
      more sensitive in detection of the immunotoxic potential of these two compounds
      in a low dose range than the examination required by OECD Guideline 407 are.

PMID- 9617633
TI  - Peroxyacetyl nitrate: review of toxicity.
AB  - PAN is one of a class of common air pollutants formed by the action of sunlight
      on volatile organic compounds and nitrogen oxides. No toxicokinetic studies have
      been found in the available literature. The acute toxicity of PAN is less than
      that of ozone, similar to NO2 and higher than SO2. The LC30, in mice and rats
      were 718-743 mg/m3 (for 2 h) and 470 mg/m3 (for 4 h), respectively. Following
      acute exposure, severe lung lesions and, at the higher levels, damage to the
      epithelium of upper parts of the respiratory tract were found in animals. It
      seems that concentrations of 1.19-1.49 mg/m3 lie not far from the threshold
      required for pulmonary function effects in sensitive individuals. However, these
      PAN concentrations are well above the maximum ambient concentrations usually
      experienced within the USA and Canada (0.003-0.078 mg/m3). It appears unlikely
      that present ambient PAN concentrations would affect pulmonary functions
      responses to ambient ozone. In human, the lowest level causing eye irritations
      was 0.64 mg/m3 for 2 h. Concentrations of 0.99 and 4.95 mg/m3 were identified as
      no-observed-effect level (NOEL) and no-observed-adverse-effect level (NOAEL) for
      pathological and histological changes in the respiratory system (nasal passages)
      of rats during subchronic exposures to PAN, but were not considered to be
      relevant to derivation of a RfC for chronic inhalation exposure. PAN is a weak
      point mutagen or clastogen. The data are not sufficient to evaluate its
      carcinogenicity. No study was found which could be used for the derivation of a
      RfC for acute or chronic inhalation exposure to PAN.

PMID- 9617634
TI  - Myocardial elements content and cardiac function after repeated i.v.
      administration of DMPS in rabbits.
AB  - 1. A dithiol chelating agent--2,3-dimercapto-1-propanesulphonate (DMPS)--may be
      administered in acute or chronic intoxication with certain heavy metals (e.g.
      cadmium, cobalt, lead) that may cause cardiotoxicity. 2. DMPS can act as a
      depleter of physiologically important elements (e.g. potassium, magnesium,
      calcium) in various tissues including cardiac one. The possibility of subsequent
      alteration in cardiac function cannot be excluded. 3. Changes in the myocardial
      concentration of the above mentioned elements at the end of the experiment and
      cardiac function were studied during repeated i.v. administration of DMPS as
      single doses of 50 mg/kg/ week for 10 weeks in rabbits. Biochemical,
      haematological and histological examinations were also performed. 4. Most of the
      measured parameters were not affected by the repeated administration of DMPS. A
      significant decrease in magnesium and a near significant decrease in calcium in
      cardiac muscle was not accompanied by functional or morphological changes. It is
      still suggested, however, that care should be taken in using DMPS for treating
      patients with cardiotoxicity as a result of poisoning with heavy metals.

PMID- 9617635
TI  - Abnormal antioxidant system in erythrocytes of mercury-exposed workers.
AB  - To investigate the effects of chronic exposure to mercury we studied the red cell
      antioxidant system in mercury-exposed workers through the evaluation of reduced
      glutathione, catalase and superoxide dismutase systems. Of these workers, some
      were being exposed at the time and had presented urinary mercury levels
      considered safe for occupational exposure for at least 3 months prior to the
      initiation of this study, and others had been on leave for at least 6 months
      because of intoxication symptoms. Reduced glutathione levels were lower and
      catalase activity was higher in the workers which were still being exposed,
      compared to those on leave and controls. No differences were observed between the
      workers on leave and controls.

PMID- 9617636
TI  - Biovolatilization of antimony and sudden infant death syndrome (SIDS).
AB  - 1. The aerobic filamentous fungus S. brevicaulis IMI 17297 methylated antimony
      from Sb2O3 substrate, with the formation of gaseous trimethylantimony (TMA). No
      evidence was found for the generation of other gaseous antimony compounds by this
      organism. 2. Biovolatilization of inorganic antimony was greatest during
      cultivation of the fungus on solid media at 25 degrees C, and occurred more
      readily from antimony (III) substrates than from antimony (V) substrates. 3.
      Under simulated cot environment conditions (CO2 enriched atmosphere, 33 degrees
      C) the fungus exhibited an altered morphology and a reduced capability to
      volatilize inorganic antimony from the pure compound. 4. No evidence of antimony
      biovolatilization from cot mattress PVC was found, unless antimony was released
      from PVC by heat treatment (at 80 or 100 degrees C). 5. These data suggest that
      normal cot environment conditions are non-optimal for volatilization of antimony
      by S. brevicaulis, and that Sb2O3 in cot mattress PVC is not bioavailable. 6. Cot
      mattress isolates of S. brevicaulis also volatilized antimony (not encapsulated
      by PVC), whereas those of other filamentous fungi (Penicillium spp., Aspergillus
      niger, Aspergillus fumigatus, Alternaria sp.) and of bacteria (Bacillus spp.) did
      not. 7. The oxidation products of TMA may be the true determinants of toxicity
      for biogenic antimony gases produced in an aerobic environment.

PMID- 9617637
TI  - A quantitative evaluation of the three dimensional reconstruction of patients'
      coronary arteries.
AB  - BACKGROUND: Through extensive training and experience angiographers learn to
      mentally reconstruct the three dimensional (3D) relationships of the coronary
      arterial branches. Graphic computer technology can assist angiographers to more
      quickly visualize the coronary 3D structure from limited initial views and then
      help to determine additional helpful views by predicting subsequent angiograms
      before they are obtained. METHODS: A new computer method for facilitating 3D
      reconstruction and visualization of human coronary arteries was evaluated by
      reconstructing biplane left coronary angiograms from 30 patients. The accuracy of
      the reconstruction was assessed in two ways: 1) by comparing the vessel's
      centerlines of the actual angiograms with the centerlines of a 2D projection of
      the 3D model projected into the exact angle of the actual angiogram; and 2) by
      comparing two 3D models generated by different simultaneous pairs on angiograms.
      The inter- and intraobserver variability of reconstruction were evaluated by
      mathematically comparing the 3D model centerlines of repeated reconstructions.
      RESULTS: The average absolute corrected displacement of 14,662 vessel centerline
      points in 2D from 30 patients was 1.64 +/- 2.26 mm. The average corrected
      absolute displacement of 3D models generated from different biplane pairs was
      7.08 +/- 3.21 mm. The intraobserver variability of absolute 3D corrected
      displacement was 5.22 +/- 3.39 mm. The interobserver variability was 6.6 +/- 3.1
      mm. CONCLUSIONS: The centerline analyses show that the reconstruction algorithm
      is mathematically accurate and reproducible. The figures presented in this report
      put these measurement errors into clinical perspective showing that they yield an
      accurate representation of the clinically relevant information seen on the actual
      angiograms. These data show that this technique can be clinically useful by
      accurately displaying in three dimensions the complex relationships of the
      branches of the coronary arterial tree.

PMID- 9617638
TI  - Coronary anomalies diagnosed with transesophageal echocardiography: complementary
      clinical value in adults.
AB  - INTRODUCTION: Coronary arteriography remains a gold standard for the evaluation
      of coronary anatomy. In the case of anatomical anomalies, understanding of vessel
      course based upon a coronary angiogram may be difficult. Transesophageal
      echocardiography is a noninvasive method allowing tomographic visualization of
      proximal coronary arteries. Experience concerning its usefulness for the
      assessment of anomalous coronary arteries is limited. MATERIAL: Eleven patients
      with confirmed coronary anomalies studied between 1993-96 were identified in the
      cohort of those undergoing transesophageal echocardiography. RESULTS:
      Transesophageal echocardiography revealed potentially serious anomalies (origin
      of left or right coronary artery from contralateral aortic sinus) in 3 patients
      and benign in 8. Coronary ostia and proximal course could be delineated in all
      patients. Anatomical information was consistent between methods, except for a
      separate origin of the left anterior descending and circumflex artery, where the
      angiogram missed a very short common left main coronary artery in 2 patients. The
      relationship between the coronary arteries, aorta and pulmonary trunk was better
      defined by the echocardiogram. Doppler flow analysis allowed us to exclude
      anomaly-related flow disturbances. CONCLUSIONS: Transesophageal echocardiography
      can be considered as a noninvasive technique with the potential for anatomical
      and functional evaluation of anomalous proximal coronary arteries and deserves a
      routine use whenever such a condition is suspected. This approach may simplify
      invasive procedures in this patient group.

PMID- 9617639
TI  - Fluorodeoxyglucose uptake in dysfunctional myocardium subtended by an occluded
      coronary artery. Relation to dobutamine contractile reserve and Sestamibi uptake.
AB  - BACKGROUND: Myocardial segments with impaired function may have the potential for
      functional recovery. Augmented exogenous glucose uptake in relation to blood flow
      estimated by [2-18F]2-fluorodeoxyglucose (FDG) and positron emission tomography
      (PET) frequently indicates functional reversibility. The spectrum of FDG uptake
      levels in relation to Sestamibi uptake and dobutamine contraction reserve in
      areas with impaired function subtended by an occluded coronary artery has never
      been reported. METHODS AND RESULTS: Seventeen patients with stable angina
      pectoris and dysfunctional myocardium subtended by an occluded coronary artery
      were studied with FDG-PET, low-dose dobutamine echocardiography and Sestamibi
      Single Photon Emission Computerized Tomography. In a 16 segment model
      dysfunctional myocardial segments showed a normally distributed FDG uptake
      ranging from 34% to 150% when normalized to peak segmental Sestamibi uptake. Low
      FDG uptake was associated with both lack of dobutamine induced contractile
      reserve and low Sestamibi uptake (in 73% of the segments) whereas high FDG uptake
      displayed both contractile reserve and Sestamibi uptake (57%). Segments with
      intermediate FDG uptake had either contractile reserve or a preserved Sestamibi
      uptake (62%). CONCLUSION: Dysfunctional myocardium subtended by an occluded
      coronary artery represents a continuum of metabolic states with a high degree of
      heterogeneity with regard to contractile reserve and Sestamibi uptake.

PMID- 9617640
TI  - Tc-99m tetrofosmin myocardial SPECT perfusion imaging: comparison of rest-stress
      and stress-rest protocols.
AB  - AIM: The purpose of this study was to evaluate the diagnostic value of Tc-99m
      tetrofosmin SPECT myocardial perfusion scintigraphy rest/stress and stress/rest
      protocols for the assessment of coronary artery disease (CAD). METHODS: 65
      patients underwent both rest and stress SPECT imaging in a one-day protocol and
      coronary angiography within 2 months before or after scintigraphy. Scintigraphic
      data was obtained according to two different protocols; 1) rest-stress (n = 18)
      and 2) stress-rest (n = 47). RESULTS: Scintigraphic evidence for myocardial
      ischaemia was found in 36 patients (55%). The overall sensitivity to detect CAD
      (> 50% luminal stenosis) was 94% (34/36), specificity 66% (19/24), positive
      predictive value 77%, negative predictive value 90%. The sensitivity to detect
      CAD for protocols 1 and 2 were 100% and 93%, specificity 56% and 70%, positive
      predictive value 69% and 81% and negative predictive value 100% and 88%,
      respectively. The left anterior descending coronary artery showed a sensitivity
      (overall, protocol 1 & 2) of 78%, 75% (3/4) and 79% (15/19) and a specificity of
      71%, 64% (9/14) and 75% (21/28). The right coronary artery showed a sensitivity
      (overall, protocol 1 & 2) of 91%, 100% (6/6) and 88% (14/16) and a specificity of
      70%, 92% (11/12) and 61% (19/31). The left circumflex coronary artery showed a
      sensitivity (overall, protocol 1 & 2) of 50%, 67% (2/3) and 46% (6/13) and a
      specificity of 94%, 100% (15/15) and 91% (31/34). CONCLUSION: Tc-99m tetrofosmin
      appears to be a valuable tool in predicting significant CAD. The sensitivity and
      the positive predictive value are high, making this test highly appropriate for
      the diagnosis of CAD. The diagnostic value of the individual coronary arteries is
      high to moderate. No significant differences were found between both protocols.

PMID- 9617641
TI  - MRI imaging of a left atrial mass misinterpreted by transesophageal
      echocardiography.
AB  - Magnetic resonance imaging of the heart was used in a patient with a history of
      recurrent episodes of transient ischemic attacks in whom a left atrial mass was
      suspected on transesophageal echocardiography. The use of MRI clarified a
      diagnosis of a diaphragmatic hernia.

PMID- 9617642
TI  - Myocardial iron deposition in beta-thalassemia studied by magnetic resonance
      imaging.
AB  - Myocardial iron deposition is a common finding in beta-thalassemia. The iron
      content of the myocardium was assessed using the T2 relaxation time of the heart.
      The T2 relaxation time of the liver and skeletal muscle was also assessed in
      order to study the relation of iron deposition between heart, liver and skeletal
      muscle. ECG gated spin echo images were obtained from thirty-eight consecutive
      adult thalassemic patients examined in an outpatient clinic, aged (x +/- SD) 25
      +/- 6 years, using a 0.5 T system. Patients were divided into groups A and B,
      according to their average serum ferritin levels of the preceding five years (>
      or < 2000 ng/ml). Results were compared with nine controls, aged 24 +/- 7 years.
      Heart T2 relaxation time in the control group (x +/- SD) (48.3 +/- 5.5 msec) was
      higher compared to group A (28.4 +/- 6.7 msec, p < 0.001) but not to group B
      (43.4 +/- 7.4 msec). The T2 relaxation time of the heart correlated positively
      with the T2 relaxation time of the liver (r = 0.68, p < 0.001) and negatively
      with ferritin levels (r = -0.67, p < 0.001). There was no correlation with the T2
      relaxation time of skeletal muscle. This study indicates that regularly
      transfused beta-thalassemia patients may present with a broad variation of heart
      iron deposition which, however, is related to serum ferritin levels.

PMID- 9617643
TI  - Embolization as a treatment of life-threatening haemoptysis in an adult with
      Tetralogy of Fallot with pulmonary atresia.
AB  - AIM: Description of embolization as a treatment for bleeding bronchopulmonary
      collaterals in congenital heart disease. METHODS: After palliative corrective
      surgery of Tetralogy of Fallot with pulmonary atresia, haemoptysis due to
      ruptured bronchopulmonary collaterals is a well known complication. We describe a
      31 year old patient with haemoptysis after incomplete correction because of
      Tetralogy of Fallot with pulmonary atresia. Because supportive treatment failed,
      the bleeding site was localized angiographically. Collaterals emerged from the
      right mammary artery, several intercostal arteries and the right costobrachial
      truncus. Embolization of these vessels with non absorbable particles stopped the
      bleeding. A follow-up of more than one year was uneventful. CONCLUSION:
      Embolization of bronchial collaterals has to be considered in patients with
      haemoptysis due to complex congenital disorders.

PMID- 9617644
TI  - In response to the article by R. Leischik et al.: Reproducibility of stress
      echocardiography using intravenous injection of ultrasound contrast agent (BY963)
      (see volume 13/5: 387-394)
AB  - Many contrast agents will soon be available to the clinicians, but as is evident,
      contrast echocardiography and the development of agents is still in its infancy.
      For successful clinical use of contrast echocardiography requires integration of:
      the development of contrast agents; modifications to ultrasound machines;
      development and validation of the specific clinical application software.

PMID- 9617645
TI  - Effective educational techniques for primary care providers: application to the
      management of psychiatric disorders.

PMID- 9617646
TI  - Teachers' experiential learning about learning.
AB  - OBJECTIVE: An experiential model of learning suggests that changing a learner's
      understanding will lead to the learner choosing to change behavior. A workshop
      was designed for medical educators to examine their understanding of learning in
      order to change their behavior as teachers. This article describes that workshop
      which was presented as part of a conference on successful techniques for
      education of primary care practitioners. METHOD: Eighteen medical educators
      participated in the workshop. The educators were instructed to reflect on a
      recent personal learning experience. Group discussion led to production of a list
      of components of effective learning. These learning components were then applied
      in small groups to three hypothetical tasks related to mental health education.
      RESULTS: Essential characteristics of three generic features of learning were
      identified: characteristics of the teacher, learner, and learning experience.
      When these characteristics were then applied to the hypothetical tasks, a major
      theme that emerged was a focus on the importance of learner motivation.
      CONCLUSIONS: The essential components of learning and their application
      demonstrate the importance of adult learning theory in which it is more important
      for the learner than for the teacher to determine what, when, and how to learn.
      This is in contrast to traditional medical education in which the teacher decides
      what to learn and if it has been learned. To improve education for practicing
      primary care providers, a shift from a teaching paradigm to a learning paradigm
      is indicated.

PMID- 9617647
TI  - Does CME work? An analysis of the effect of educational activities on physician
      performance or health care outcomes.
AB  - OBJECTIVE: To answer the question, "does CME work?" by reviewing the
      effectiveness of continuing medical education (CME) and other related educational
      methods on objectively-determined physician performance and/or health care
      outcomes. These interventions include educational materials, formal, planned CME
      activities or programs, outreach visits such as academic detailing, opinion
      leaders, patient-mediated strategies, audit and feedback, reminders, or a
      combination of these strategies. METHODS: MEDLINE, ERIC, NTIS, the Research and
      Development Resource Base in CME and other relevant data sources including review
      articles were searched for relevant terms, from 1975 to 1994. Of those articles
      retrieved, randomized controlled trials of educational strategies or
      interventions which objectively assessed physician performance and/or health care
      outcomes were selected for review. Data were extracted from each article about
      the specialty of the physician targeted, the clinical subject of the
      intervention, the setting and the nature of the educational method, and the
      presence or degree of needs assessment or barriers to change. RESULTS: More than
      two-thirds of the studies (70%) displayed a change in physician performance,
      while almost half (48%) of interventions produced a change in health care
      outcomes. Community-based strategies such as academic detailing (and to a lesser
      extent, opinion leaders), practice-based methods such as reminders and patient
      mediated strategies, and multiple interventions appeared to be most effective
      activities. Mixed results and weaker outcomes were demonstrated by audit and
      educational materials, while formal CME conferences without enabling or practice
      reinforcing strategies, had relatively little impact. CONCLUSION: Strategies
      which enable and/or reinforce appear to "work" in changing physician performance
      or health care outcomes, a finding which has significant impact on the delivery
      of CME, and the need for further research into physician learning and change.

PMID- 9617648
TI  - Comprehensive, technology-based clinical education: the "virtual practicum".
AB  - This article discusses the application of technology to promote more
      comprehensive clinical education in the biopsychosocial aspects of primary care.
      Comprehensive refers to the inclusion, in addition to scientific and technical
      knowledge, of knowledge that is less easily characterized, quantified, and
      taught: empathy, intuition, the demonstration of artistry. Clinical education
      will be increasingly facilitated by the proliferation of computers capable of
      displaying combinations of text, graphics, video, and sound; broadband networks
      capable of delivering these multiple media to the home or office; and new methods
      for using these technologies for education and training. However, current models
      for technology-based learning are limiting, lagging behind the rapid
      technological evolution driving our entry into the Information Age. Some recent
      educational models (Schon's reflection-in-action and reflective practicums [1],
      Boisot's E-space [2], Kolb's learning cycle [3]) provide for a more comprehensive
      and complete view of health professional education. This article describes these
      models in depth and proposes a new model for technology-based clinical training,
      the "Virtual Practicum," based on them. The Virtual Practicum is illustrated with
      a new interactive CD-ROM program, dealing with primary care of patients with
      HIV/AIDS. The concepts presented here are generally useful in thinking about
      clinical education, regardless of the means used.

PMID- 9617649
TI  - Principles and uses of academic detailing to improve the management of
      psychiatric disorders.
AB  - OBJECTIVE: The purpose of this article is to discuss the principles of academic
      detailing, or educational outreach, in primary care and review the evidence of
      its effectiveness in, and potential for improving, mental health care. METHODS:
      The general educational research literature on improving physician performance
      was reviewed along with studies that were designed to test academic detailing.
      Four rigorous studies have tested this approach specifically on mental health
      care. These studies are reviewed in detail. RESULTS: Measuring pre-intervention
      performance to target those with increased educational needs and identifying
      barriers to change are associated with substantially improved program
      effectiveness. To change strongly held beliefs or to overcome patient demands,
      person-to-person contact with credible experts who provide structured
      alternatives is necessary. Brief reinforcement visits increase success rates and
      targeting programs to physicians at greatest need improves the cost effectiveness
      of educational interventions. CONCLUSIONS: Academic detailing is one of the few
      educational interventions that has consistently demonstrated improved physician
      performance. Educational outreach methods to improve mental health practices in
      primary care are in need of much additional research. Improving the detection of
      mental disorders and underuse of mental health treatment may prove to be more
      difficult than reducing the overuse of unnecessary medications.

PMID- 9617650
TI  - Small group interactive techniques utilizing videofeedback.
AB  - OBJECTIVE: Development and evaluation of a method of training primary care
      providers in psychiatric skills which utilizes videofeedback of real and role
      played consultations in a group setting. METHOD: The development of the basic
      training approach and additional material for teaching specific skills is
      described. Evaluation has addressed the impact of training on 1) clinician
      behavior and 2) measures of outcome. RESULTS: Research over a number of years has
      demonstrated an impact on clinician behavior with some evidence of impact on
      clinical and economic measures and patient satisfaction. CONCLUSIONS:
      Videofeedback training appears to be most effective when it is provided with a
      clear model for the professional-patient interaction. Its effectiveness can be
      further enhanced by delineating sets of component microskills that can be learned
      using a combination of videotape modeling, role-play, and feedback. Challenges
      for future research include investment in randomized controlled trials for
      outcome, developing the training approach for a range of primary care workers,
      training sufficient group facilitators, and achieving widespread dissemination
      without subsequent dilution of effectiveness.

PMID- 9617651
TI  - The challenge of "teaching" large groups of learners: strategies to increase
      active participation and learning.
AB  - While teaching in a tutorial, seminar, or problem-based learning group format may
      be the most fun and most active/interactive for both learner and faculty mentor,
      there are situations in medical student education in which various constraints
      require the use of the "lecture" format. Similar constraints may occur in the
      field of continuing medical education, or graduate medical education, as well.
      When this occurs, the faculty mentor can increase the active participation of the
      learners in the audience by continuously stressing seven key pedagogical
      (androgogical) principles. These include: 1) begin the learning exercise with a
      clinical example or anecdote to show the relevance of the material to the
      student; 2) frequently ask the students whether they have ever seen examples of
      what you describe in their previous experience with patients, personal
      experience, experience with relatives, etc.; 3) ask students frequently whether
      they have heard similar material presented differently in other courses; 4)
      recruit students to help solve "mystery cases"; 5) show examples of similar
      material from real life (e.g., patient descriptions, or even excerpts from
      favorite TV shows); 6) ask students to help summarize key points at the end of
      the session; and 7) allow, or even encourage, whispering during the class. Using
      some or all of these techniques can help turn a "lecture format" into a much more
      fun, interactive, and valuable session that emphasizes "learning" rather than
      "teaching."

PMID- 9617652
TI  - Meeting the needs of primary care physicians: a guide to content for programs on
      depression.
AB  - OBJECTIVE: The purpose of this article is to identify literature-based content
      for the design of educational programs on depression for practicing primary care
      physicians. METHODS: A MEDLINE search was conducted of English-language medical
      literature published from 1982 through July 1997 for studies describing primary
      care physicians' knowledge, skills, practice patterns, and perceived barriers
      related to care of depressed patients. Studies focusing exclusively on residency
      training and those describing physician practices outside North America were
      excluded. Of 377 articles identified, forty met inclusion and exclusion criteria.
      RESULTS: Recommendations for educational content were identified from the
      literature review. For recognition, educators should prioritize communication
      skills and strategies for the use of depression questionnaires. For diagnosis,
      practice interpreting symptoms in the medically ill, strategies for efficient
      diagnosis, and systematic approaches to assessing suicide risk should be
      emphasized. For treatment, greater attention to the therapeutic alliance, staged
      therapy, and strategies for improving medication adherence are indicated.
      CONCLUSIONS: There is a moderately well developed literature describing self
      perceived and observed gaps in the current care for depression in primary care.
      Addressing the entire list of needs would take more time than practicing
      physicians are likely to have. An important challenge for educators is to design
      flexible programs based on individualized needs assessment or, when not possible,
      to prioritize the most generalizable needs.

PMID- 9617653
TI  - Training the trainers: substance abuse screening and intervention.
AB  - OBJECTIVE: Screening and brief intervention for substance abuse is effective yet
      underutilized by primary care physicians. This article reports on Project SAEFP
      (Substance Abuse Education for Family Physicians), which aimed to enhance the
      clinical and teaching skills and activities of U.S. family practice residency
      faculty. METHOD: Ten five-day workshops were designed and administered for 165
      participants. Evaluation data included measures of participant satisfaction and
      pre-workshop and twelve-month post-workshop measures of the frequency of
      teaching, consulting, and clinical activities, and the attainment of self
      identified teaching goals. RESULTS: The participants were very satisfied with the
      workshops. They improved significantly in the key outcome measures. CONCLUSIONS:
      Several workshops may have contributed to the apparent success of Project SAEFP.
      Attributes of the workshops which might have facilitated their success were their
      duration, funding, frequency of offering, collegial learning environment,
      opportunities for active learning, emotionally moving exposure to recovering
      individuals, focus on how to modify curriculum at participant residency programs,
      availability of family physician role models as faculty, and readily usable
      instructional materials. Planners of interventions for physician educators might
      profit from similar attention to these attributes.

PMID- 9617654
TI  - Identification and restoration of lapsed skills for primary care providers.
AB  - OBJECTIVE: Individualized educational programs based upon structured
      comprehensive evaluations have the highest opportunity for success in addressing
      the needs of physicians with lapsed skills. The purpose of this article is to
      describe the Physician Prescribed Educational Program (PPEP), an integrated
      series of programs that incorporate a formalized, structured evaluation strategy.
      METHODS: The PPEP is structured to determine: 1) The presence of deficits which
      are amenable to educational remediation, 2) The likelihood that an appropriate
      educational program can be developed, and 3) The structure of such a program.
      RESULTS: Of 300 referrals, 100 have received evaluations thus far. A wide range
      of deficits were addressable, although there were specific exclusions to
      participation. CONCLUSIONS: Administrators and others who wish to undertake these
      efforts should avail themselves of educational and other resources but should not
      expect rapid results. With careful planning and execution, these programs can
      provide appropriate and successful experiences for participants.

PMID- 9617655
TI  - [Optimal reperfusion therapy in acute myocardial infarction: time to reperfusion
      and recanalization rate].
AB  - Rapid and complete reperfusion is important for the reduction of infarct size and
      mortality in acute myocardial infarction. The optimum reperfusion therapy with
      regard to the recanalization rate and the time elapsing between onset and
      complete reperfusion was evaluated. One hundred fifty-four patients with total
      occlusion of the infarct-related artery within 6 hours of the onset were
      classified into four therapy groups: PTCA group (n = 58) undergoing primary
      percutaneous transluminal coronary angioplasty (PTCA), t-PA-IC group (n = 44)
      receiving tissue plasminogen activator (t-PA) intracoronary infusion, t-PA-IV
      group (n = 14) receiving intravenous t-PA infusion, and mt-PA-IV group (n = 38)
      receiving intravenous mutant t-PA infusion. Although the recanalization rate was
      high in the PTCA group, there were no differences between the four groups as a
      supplement to immediate or rescue PTCA. The time elapsing between initiation of
      thrombolysis and complete reperfusion was shorter in the mt-PA-IV group than in
      the t-PA-IV group. Assuming the time from hospital arrival to initiation of
      intravenous thrombolysis was 20 min, the recanalization rate at 60 min after
      arrival in hospital was higher in the mt-PA-IV group than the PTCA and t-PA-IC
      groups. Although additional coronary angiography and PTCA may be required to
      improve the low recanalization rate compared with primary PTCA, intravenous
      infusion of mutant t-PA was the most promising therapy to achieve early
      reperfusion.

PMID- 9617656
TI  - [Palmaz-Schatz stent implantation for aorto-ostial stenoses of native coronary
      arteries and saphenous vein grafts].
AB  - Conventional balloon angioplasty treatment of aorto-ostial stenoses in native
      coronary arteries and saphenous vein grafts is associated with a low primary
      success rate, a high complication rate and a high incidence of restenosis. The
      short-term outcome of Palmaz-Schatz stent implantation in aorto-ostial lesions
      was compared with that of balloon angioplasty. Thirteen patients underwent stent
      implantation for 13 de novo lesions (four in the left main coronary trunk, two in
      the right coronary artery, seven in the vein graft) between January 1994 and
      December 1995. Fourteen patients underwent balloon angioplasty for 14 de novo
      lesions (five in the left main coronary trunk, four in the right coronary artery,
      five in the vein graft between January 1986 and April 1992. Both groups had
      similar clinical characteristics. Initial success was obtained in all patients in
      the stent group, compared with 71% of the balloon angioplasty group. Insufficient
      dilation was the main cause for such failure in the balloon angioplasty group.
      Baseline reference diameters were similar (3.40 +/- 0.65 mm in the stent group vs
      3.36 +/- 0.42 mm in the balloon angioplasty group) and there was no difference in
      baseline minimal luminal diameter (1.41 +/- 0.74 vs 1.08 +/- 0.56 mm). Minimal
      luminal diameter was significantly greater in the stent group than in the balloon
      angioplasty group at both post-procedure and follow-up examinations (post: 3.36
      +/- 0.58 vs 2.69 +/- 0.45 mm, p < 0.01; follow-up: 2.33 +/- 0.96 vs 1.52 +/- 0.68
      mm, p < 0.05). There was no subacute occlusion in either group. The overall
      angiographic restenosis rate (> 50% stenosis) was lower in the stent group (17%)
      than in the balloon angioplasty group: the restenosis rates of native lesions
      were 0% in the stent group and 40% in the balloon angioplasty group; those of
      saphenous vein graft lesions were 33% in the stent group and 50% in the balloon
      angioplasty group. Although the number of patients was limited, these results
      suggest that Palmaz-Schatz stent implantation may be a safe and effective
      strategy for treating aorto-ostial lesions in both native coronary arteries and
      saphenous vein grafts.

PMID- 9617657
TI  - [Mechanism and clinical usefulness of S4-S1 interval in heart failure associated
      with left ventricular inflow pattern].
AB  - The interval between S4 and S1 detected by auscultation or phonocardiography is
      prolonged by exacerbation and shortened by improvement of heart failure. The
      timing of S4, S1, and the terminal point of the A wave of transmitral inflow
      velocities on pulsed Doppler echocardiography (At) was studied to elucidate the
      mechanism of the prolongation of the S4-S1 interval on exacerbation of heart
      failure. The study population consisted of 30 patients, nine with old myocardial
      infarction, six with dilated cardiomyopathy, six with hypertensive heart disease,
      nine with chronic hemodialysis, and 17 normal subjects. The interval from the
      peak of the A wave by apexcardiography and At to the onset of main vibration of
      S1 were measured as the S4-S1 interval and At-S1 interval, respectively. The P-Q
      interval and Q-S1 interval were also measured. Both intervals were compared
      during exacerbation and improvement of heart failure. Patients with P-Q
      prolongation were excluded. The S4-S1 interval was 102 +/- 24 msec during
      exacerbation of heart failure or before hemodialysis, and shortened to 76 +/- 18
      msec after improvement of heart failure or after hemodialysis. The At-S1 interval
      was concordantly shortened from 59 +/- 31 msec to 30 +/- 23 msec (p < 0.001).
      However, both the P-Q interval and Q-S1 interval were not significantly changed
      before and after improvement of heart failure. The timing of S4 becomes parallel
      to that of At earlier during the exacerbation of heart failure. Thus, S4-S1
      interval is a convenient and useful index to investigate patients with heart
      failure.

PMID- 9617658
TI  - [Evaluation of whole blood rapid troponin T assay: cooperative study of general
      practitioners and office cardiologists in Tokyo].
AB  - The recently developed whole blood rapid assay for cardiac troponin T (TROP T)
      was evaluated by a cooperative study of general practitioners and office
      cardiologists in the Tokyo area (Tokyo TROP T Trial). Seventy patients with
      suspected acute myocardial infarction treated at 14 medical clinics were enrolled
      in this study. The diagnostic efficacy of troponin T was compared with that of
      electrocardiographic evaluations and clinical standards for diagnosis of acute
      myocardial infarction. Twelve of the 70 patients (17.1%) had final diagnoses of
      acute myocardial infarction or severe unstable angina necessitating emergency
      coronary intervention. Troponin T was judged as positive when simultaneously
      measured serum troponin T was more than 0.25 ng/ml. Sensitivity, specificity,
      positive predictive value, and negative predictive value were 100%, 58.6%, 33.3%,
      and 100% for electrocardiographic evaluation, and 58.3%, 100%, 100%, and 92.1%
      for troponin T, respectively. Presence of bundle branch block (11/70 cases) or
      previous myocardial infarction (14/70 cases) caused false positive readings on
      electrocardiography, and resulted in the lower positive predictive value. In
      contrast, troponin T was false in patients admitted within 4 hours after the
      onset, or patients with smaller infarct. The Tokyo TROP T Trial by general
      practitioners and office cardiologists concluded that the combination of
      electrocardiographic evaluation and use of troponin T is a rapid and efficient
      diagnostic method for the evaluation of patients with suspected acute myocardial
      infarction.

PMID- 9617659
TI  - Progression to moderate or severe mitral regurgitation after percutaneous
      transvenous mitral commissurotomy using stepwise inflation technique.
AB  - Progression to moderate or severe mitral regurgitation (MR) was studied after
      Inoue balloon percutaneous transvenous mitral commissurotomy (PTMC) using the
      stepwise inflation technique, performed at increments of 1 mm of balloon
      diameter, in 49 consecutive patients with rheumatic mitral stenosis (aged from 32
      73 years; 8 males, 41 females). The patients were classified on the basis of the
      degree of MR after PTMC, compared with that before PTMC, into either Group A,
      development of moderate or more severe (> or = grade 2) MR (n = 8) or Group B, no
      increase in MR or development of mild (grade 1) MR (n = 41). Progression to
      moderate or severe MR was significantly associated only with advanced age (60 +/-
      8 vs 52 +/- 10 years, p < 0.05) and narrower mitral valve area (0.87 +/- 0.35 vs
      1.11 +/- 0.29 cm2, p < 0.05), but other characteristics before PTMC were similar
      in both groups. There was no difference between the two groups in the total
      number and degree of balloon inflation. Immediately before the final inflation,
      the left atrial mean pressure and v wave pressure were decreased in smaller
      degrees in Group A compared with Group B (-2 +/- 2 vs -5 +/- 4 mmHg, p < 0.05; -2
      +/- 2 vs -6 +/- 6 mmHg, p < 0.05, respectively). Thus, the stepwise inflations
      require careful monitoring of changes in the left atrial pressure and waveform to
      recognize the aggravation of MR, especially in older patients with severe
      stenosis. Patients who do not have a significant drop in left atrial mean
      pressure and v wave pressure during stepwise inflations of the balloon might be
      at risk of development of moderate or severe MR after further dilations.

PMID- 9617660
TI  - [Sudden death during Holter electrocardiographic monitoring in a patient with
      hypertrophic cardiomyopathy].
AB  - A 56-year-old man visited a doctor because of arrhythmia and a diagnosis of
      hypertrophic cardiomyopathy was made in 1990. On January 9th, 1997, when aged 63
      years old, he visited another doctor because of paroxysmal atrial fibrillation
      tachycardia. Since his clinical symptoms did not ameliorate, he visited our
      hospital on April 14th, and Holter electrocardiographic monitoring was started on
      April 16th. While walking on the street, his heart rate increased up to 107
      beat/min when premature ventricular contraction with a long coupling interval of
      400 msec occurred, followed by polymorphous ventricular tachycardia, ventricular
      fibrillation and death. He had no risk factors for sudden death such as early
      onset of symptoms, history of syncope, family history of sudden death, documented
      ventricular tachycardia, and congestive heart failure. Although many cases of
      hypertrophic cardiomyopathy end in sudden death, no electrocardiographic
      recordings at the time of sudden death have been available. This is the first
      case of electrocardiographic recording at the time of sudden death in a patient
      with hypertrophic cardiomyopathy.

PMID- 9617662
TI  - [Cardiovascular imaging in-a-month. Asymptomatic cardiac mass].

PMID- 9617661
TI  - [Hypertrophic obstructive cardiomyopathy in an elderly patient manifesting as
      refractory congestive heart failure of acute onset: a case report].
AB  - An 84-year-old woman was admitted to our hospital because of left heart failure
      of acute onset. Transthoracic echocardiography showed diffuse hypertrophy of the
      normal sized hyperkinetic left ventricle and chordae-like fluttering echoes
      attached to the mitral valve with severe mitral regurgitation signals. Mosaic
      flow signals were seen at the left ventricular outflow tract, but the velocity
      could not be measured. Emergent transesophageal echocardiography detected no
      obvious mitral valve prolapse. Cardiac catheterization showed greater than 100
      mmHg pressure gradient between the left ventricle and femoral artery. Pressures
      in the femoral artery and pulmonary capillary wedge changed reciprocally in the
      intensive care unit; a bisferient narrow pulse pressure of the femoral artery was
      associated with increased v wave of the pulmonary capillary wedge pressure, and a
      wide pulse pressure of the femoral artery with absent v wave of the pulmonary
      capillary wedge pressure. Pressure monitoring in the intensive care unit,
      catheterization laboratory and transesophageal echocardiography were useful to
      understand the pathophysiology of the patient.

PMID- 9617663
TI  - Modulation of burst frequency by calcium-dependent potassium channels in the
      lamprey locomotor system: dependence of the activity level.
AB  - It is crucial to determine the effects on the network level of a modulation of
      intrinsic membrane properties. The role calcium-dependent potassium channels,
      KCa, in the lamprey locomotor system has been investigated extensively. Earlier
      experimental studies have shown that apamin, which affects one type of KCa,
      increases the cycle duration of the locomotor network, due to effects on the
      burst termination. The effects of apamin were here larger when the network had a
      low level of activity (burst frequency 0.5 to 1 Hz) as compared to a higher rate
      (> 2 Hz). By using a previously developed simulation model based on the lamprey
      locomotor network, we show that the model could account for the frequency
      dependence of the apamin modulation, if only the KCa conductance activated by
      Ca2+ entering during the action potential was altered and not the KCa conductance
      activated by Ca2+ entering through NMDA channels. The present simulation model of
      the spinal network in the lamprey can thus account for earlier experimental
      results with apamin on the network and cellular level that previously appeared
      enigmatic.

PMID- 9617664
TI  - Reduction of presynaptic action potentials by PAD: model and experimental study.
AB  - A compartmental model of myelinated nerve fiber was used to show that primary
      afferent depolarization (PAD), as elicited by axo-axonic synapses, reduces the
      amplitude of propagating action potentials primarily by interfering with ionic
      current responsible for the spike regeneration. This reduction adds to the effect
      of the synaptic shunt, increases with the PAD amplitude, and occurs at
      significant distances from the synaptic zone. PAD transiently enhances the sodium
      current activation, which partly accounts for the PAD-induced fiber
      hyperexcitability, and enhances sodium inactivation on a slower time course, thus
      reducing the amplitude of action potentials. In vivo, intraaxonal recordings from
      the intraspinal portion of group I afferent fibers were carried out to verify
      that depolarizations reduced the amplitude of propagating action potentials as
      predicted by the model. This article suggests PAD might play a major role in
      presynaptic inhibition.

PMID- 9617665
TI  - Associative memory and segmentation in an oscillatory neural model of the
      olfactory bulb.
AB  - We discuss the first few stages of olfactory processing in the framework of a
      layered neural network. Its central component is an oscillatory associative
      memory, describing the external plexiform layer, that consists of inhibitory and
      excitatory neurons with dendrodendritic interactions. We explore the
      computational properties of this neural network and point out its possible
      functional role in the olfactory bulb. When receiving a complex input that is
      composed of several odors, the network segments it into its components. This is
      done in two stages. First, multiple odor input is preprocessed in the glomerular
      layer via a decorrelation mechanism that relies on temporal independence of odor
      sources. Second, as the recall process of a pattern consists of associative
      convergence to an oscillatory attractor, multiple inputs are identified by
      alternate dominance of memory patterns during different sniff cycles. This could
      explain how quick analysis of mixed odors is subserved by the rapid sniffing
      behavior of highly olfactory animals. When one of the odors is much stronger than
      the rest, the network converges onto it, thus displaying odor masking.

PMID- 9617666
TI  - Analysis and neural network modeling of the nonlinear correlates of habituation
      in the vestibulo-ocular reflex.
AB  - Through the process of habituation, continued exposure to low-frequency (0.01 Hz)
      rotation in the dark produced suppression of the low-frequency response of the
      vestibulo-ocular reflex (VOR) in goldfish. The response did not decay gradually,
      as might be expected from an error-driven learning process, but displayed several
      nonlinear and nonstationary features. They included asymmetrical response
      suppression, magnitude-dependent suppression for lower- but not higher-magnitude
      head rotations, and abrupt-onset suppressions suggestive of a switching
      mechanism. Microinjection of lidocaine into the vestibulocerebellum of habituated
      goldfish resulted in a temporary dishabituation. This suggests that the
      vestibulocerebellum mediates habituation, presumably through Purkinje cell
      inhibition of vestibular nuclei neurons. The habituated VOR data were simulated
      with a feed-forward, nonlinear neural network model of the VOR in which only
      Purkinje cell inhibition of vestibular nuclei neurons was varied. The model
      suggests that Purkinje cell inhibition may switch in to introduce
      nonstationarities, and cause asymmetry and magnitude-dependency in the VOR to
      emerge from the essential nonlinearity of vestibular nuclei neurons.

PMID- 9617667
TI  - The analysis of synaptically generated traveling waves.
AB  - Mathematical and computational models for the propagation of activity in
      excitatorily coupled neurons are simulated and analyzed. The basic measurable
      quantity--velocity--is found for a wide class of models. Numerical bifurcation
      techniques, asymptotic analysis, and numerical simulations are used to show that
      there are distinct scaling laws for the velocity as a function of a variety of
      parameters. In particular, the obvious linear relationships between speed and
      spatial spread or synaptic decay rate are shown. More surprisingly, it is shown
      that the velocity scales as a power law with synaptic coupling strength and that
      the exponent is dependent only on the rising phase of the synapse.

PMID- 9617668
TI  - Simulation and parameter estimation study of a simple neuronal model of rhythm
      generation: role of NMDA and non-NMDA receptors.
AB  - Simple neural network models of the Xenopus embryo swimming CPG, based on the one
      originally developed by Roberts and Tunstall (1990), were used to investigate the
      role of the voltage-dependent N-methyl-D-aspartate (NMDA) receptor channels, in
      conjunction with faster non-NMDA components of synaptic excitation, in rhythm
      generation. The voltage-dependent NMDA current "follows" the membrane potential,
      leading to a postinhibitory rebound that is more efficient than one without
      voltage dependency and allows neurons to fire more than one action potential per
      cycle. Furthermore, the model demonstrated limited rhythmic activity in the
      absence of synaptic inhibition, supporting the hypothesis that the NMDA channels
      provide a basic mechanism for rhythmicity. However, the rhythmic properties
      induced by the NMDA current were observed only when there was moderate activation
      of the non-NMDA synaptic channels, suggesting a modulatory role for this
      component. The simulations also show that the voltage dependency of the NMDA
      conductance, as well as the fast non-NMDA current, stabilizes the alternation
      pattern versus synchrony. To verify that these effects and their implications on
      the mechanism of swimming and transition to other types of activity take place in
      the real preparation, constraints on parameter values have to be specified. A
      method to estimate synaptic parameters was tested with generated data. It is
      shown that a global analysis, based on multiple iterations of the optimization
      process (Foster et al., 1993), gives a better understanding of the parameter
      subspace describing network activity than a standard fit with a sensitivity
      analysis for an individual solution.

PMID- 9617669
TI  - Comparative densitometric study of iliac crest and scapula bone in relation to
      osseous integrated dental implants in microvascular mandibular reconstruction.
AB  - The study was designed to compare dimension and density of four frequently used
      bone donor regions (the iliac crest, the lateral border of the scapula, the
      radius and the fibula) with regard to placement of endosseous dental implants in
      microvascular mandibular reconstruction. The first part of the study reports on
      the results of bone dimension and density findings for iliac crest and scapula
      bone. Nearly all of the iliac crests had adequate dimensions for the positioning
      of four 10 mm implants. In 63% of the scapulae, it was possible to place four 10
      mm implants. In the case of the scapula, half of the female subjects lacked
      enough available bone for the insertion of four 10 mm implants because of their
      inadequate width. Bone density and cortical thickness was found to be similar in
      the iliac crest and scapula. Age and side do not have an important influence on
      cortical bone dimensions and density. In contrast to the iliac crest, the lateral
      margin of the scapula astonishingly showed increasing values for bone density and
      increasing thickness of the cortex. Analogical advanced biological age works in
      conformity with the scapula flap. The results could, together with other clinical
      criteria, contribute to the choice of the best individual alternative in
      mandibular reconstruction.

PMID- 9617670
TI  - Surgical landmarks of the infratemporal fossa.
AB  - Surgical interventions on the infratemporal fossa require an accurate knowledge
      of the surgical anatomy. Thirty-four adult human skulls were examined and
      measurements made of the distance between the zygomatic arch and the root of the
      lateral pterygoid plate. The distance between the central part of the lateral and
      medial pterygoid plates was also measured. The first measurement represents the
      distance of the foramen ovale from the zygoma; the average being 38.2 mm. The
      average distance between the pterygoid plates is 9.6 mm. Addition of these two
      measurements represents the distance of the lateral wall of the nasopharynx from
      the zygoma and the average is 47.8 mm. Together with the knowledge of the
      arrangement of the muscle layers and the nerves and vessels in this region, this
      information has proved useful in the surgery of the area.

PMID- 9617671
TI  - Biodegradable polylactide plates and screws in orthognathic surgery: technical
      note.
AB  - In orthognathic surgery, the bone fragments are usually fixed with metallic
      plates and screws. Metallic devices other than titanium plates are usually
      removed after the osteotomy has consolidated, which often requires general
      anaesthesia. Titanium plates, supposed to be biotolerable, have been introduced
      in order to overcome this need for secondary intervention. However, due to
      corrosion, titanium particles have been found in scar tissue covering these
      plates and in locoregional lymph nodes. Therefore, their removal is also
      advocated. Self-reinforced poly (L-lactide) homopolymer (PLLA) and poly (L/D
      lactide) stereocopolymers with a L/D molar ratio up to 85/15 have sufficient
      strength to overcome the need for additional support for the fixation of
      fractures. The plates can be bent at room temperature. The surgical technique and
      early results of a case of bimaxillary surgery and genioplasty fixed with
      bioresorbable material without postoperative rigid maxillomandibular fixation are
      reported.

PMID- 9617672
TI  - Mandibulo-facial dysostosis: comparison study of a neonate with mandibulo-facial
      dysostosis and a normal neonate.
AB  - Mandibulo-facial dysostosis (MFD) is a malformative syndrome with autosomal
      dominant transmission and variable expressivity that mainly affects derivatives
      of the first and second branchial arches. The subsurface anatomy of this
      condition is still partly unexplored since there have been only four reported
      dissections of MFD. A detailed dissection of the head and neck of a neonate with
      MFD is described and compared with a normal neonate. Theories of the pathogenesis
      are discussed on the basis of these observations.

PMID- 9617673
TI  - Osteosarcoma of the maxillofacial bones in Kenyans.
AB  - Osteosarcoma (OS) is a highly malignant tumour and is the most common primary
      neoplasm of bone; although rare, especially in the maxillofacial skeleton. This
      article presents 14 Kenyan cases of OS of the maxillofacial bones seen between
      January 1991 and July 1997: 11 in the mandible, two in the maxilla and one in the
      right zygomatic arch. Patients ranged in age from one week to 50 years (Mean =
      29.7), with an equal gender distribution. While pain and rapid swelling were the
      commonest clinical features, the radiographic and histopathological
      characteristics were as varied as has been described elsewhere. Generally,
      effective management of most of the cases was poor due to late presentation for
      treatment.

PMID- 9617674
TI  - Congenital plate-like osteoma cutis of the forehead: an atypical presentation
      form.
AB  - Cutaneous ossifications or osteoma cutis can be found in many syndromes. Primary
      osteoma cutis, present since birth or the first months of life, in the absence of
      metabolic disorders or trauma, is found in congenital plate-like osteoma cutis
      and progressive osseous heteroplasia, coexisting in the latter with deep
      connective tissue ossifications. This report documents the case of a 7-year-old
      female with a plate-like cutaneous ossification of the forehead causing aesthetic
      deformities. Other dermal ossifications in the inguinal and preauricular region,
      as well as the left hand and a small focus in the extraocular muscles of the left
      orbit, were also present. These lesions did not show progression, and most of
      them were present since birth. The lesion of forehead was treated surgically. The
      lack of progression and the fact that the orbital lesion was solitary still fits
      the criteria for the diagnosis of plate-like osteoma cutis. Plate-like osteoma
      cutis and progressive osseous heteroplasia may represent varieties of the same
      disorder.

PMID- 9617675
TI  - Quantitative evaluation of consistency of normal mucosa, leukoplakia and squamous
      cell carcinoma of the tongue.
AB  - The quantitative differences in consistency of normal mucosa, leukoplakia and
      squamous cell carcinoma of the tongue were studied. Forty-five patients with
      squamous cell carcinoma of the tongue, 26 with leukoplakia and 80 with normal
      tongues were examined using an instrument capable of measuring consistency as a
      function of the load (in grams) needed to displace tongue mucosa by 2.0 mm using
      a probe 2.0 mm in diameter. The mean value for consistency in tongue carcinoma,
      leukoplakia and normal tongue was 22.1 +/- 8.0 g, 8.3 +/- 2.0 g and 4.8 +/- 0.7
      g, respectively. Differences in consistency among these entities were significant
      (P < 0.001). Furthermore, consistency in tongue carcinoma was significantly
      correlated to tumour thickness (r = 0.954, P < 0.001). It was concluded that the
      consistency in tongue lesions was objectively and quantitatively evaluated by
      this method, and this technique could measure the thickness of the tumorous
      lesions preoperatively.

PMID- 9617677
TI  - Osseous regeneration in the jaws using demineralized allogenic bone implants.
AB  - Osseous defects of the jaws following trauma, congenital deformity or pathology
      may show poor osteogenesis and the affected area may never be completely replaced
      by bone or will show alveolar height loss. The purpose of the present study was
      to evaluate the effect of allogenic bone implants (ABI) on the osteogenesis of
      jaw defects. Fifty-two patients (27 males, 25 females) with cystic lesions of the
      jaws were randomly divided into two groups: Group A underwent enucleation and
      packing with adsorbable gelatine sponge. Group B underwent enucleation and
      grafting with ABI. Both groups were evaluated radiographically. The height of the
      alveolar process was measured directly on the radiography. The density was
      measured with a digital densitometer. In Group A, the mandibular height at 6, 12
      and 24 months postoperatively was 88%, 80% and 78% of the preoperative heights,
      respectively. In Group B, the heights were 95%, 93% and 90%, respectively. These
      differences were significant (P < 0.05-0.01). The density in Group B was
      significantly greater (P < 0.05-0.01) than in Group A at 6 and 12 months
      postoperatively. The difference at 24 months was not significant. On the basis of
      these findings, it can be concluded that ABI grafting of jaw defects enhances
      osteogenesis and prevents alveolar height loss in the mandible. ABI represent an
      encouraging alternative to autogenous bone grafting.

PMID- 9617676
TI  - Osteoinduction capability of recombinant human bone morphogenetic protein-2 in
      intramuscular and subcutaneous sites: an experimental study.
AB  - The osteoinduction capability of recombinant human bone morphogenetic protein-2
      (rhBMP-2) in the muscle and in the subcutaneous tissue in Wistar rats (n = 20)
      was evaluated, using atelopeptide type-I collagen as a carrier. The alkaline
      phosphatase (ALP) activity and calcium (Ca) content were quantitatively analyzed
      1, 3, 7 and 21 days after the implantation of 5 micrograms of rhBMP-2. At 3 days,
      the ALP activity began to increase gradually. The Ca content showed a slow
      increase until 7 days and was markedly elevated at 21 days. There was no
      significant difference observed between the intramuscular and subcutaneous sites
      until 3 days. However, at 7 days, both the ALP activity and Ca content were
      significantly higher intramuscularly than subcutaneously. Also, at 21 days they
      were higher in the muscle than in the subcutaneous tissue. These results suggest
      that the difference in osteoinduction could be related to the partial pressure of
      oxygen or the blood supply in the intramuscular and subcutaneous sites, and that
      immature mesenchymal cells in the muscle could more easily differentiate into
      osteoblasts, leading to osteoinduction. This study clearly demonstrated that even
      a small amount (5 micrograms) or rhBMP-2 induces new bone in the subcutaneous
      tissue, which has a lesser blood flow than the muscle.

PMID- 9617678
TI  - Preoperative autologous blood donation in orthognathic surgery: a follow-up study
      of 179 patients.
AB  - Although there have been recent advances in maxillofacial surgery and anaesthetic
      techniques, blood replacement is still common in orthognathic surgery. 179
      patients underwent elective orthognathic surgery and donated autologous blood
      preoperatively. Standardized questionnaires about the preoperative blood donation
      were distributed to the patients. Haemoglobin, haematocrit, red blood cells and
      platelets were measured before blood donation, presurgically and postsurgically,
      as well as one year after surgery. Nearly all patients (98%) would recommend
      preoperative autologous blood donation. 97% of the patients saw the benefits of
      autologous blood donation in avoiding transfusion-transmitted infectious diseases
      such as acquired immune deficiency syndrome (AIDS) and hepatitis. No serious side
      effects have been observed after blood donation. In patients with bimaxillary
      osteotomies (65% of the predeposited autologous blood units) 41% were in cases
      having upper jaw osteotomies and only 22% of the preoperatively donated units
      were retransfused in patients having lower jaw osteotomies. After a postsurgical
      decrease, the mean haemoglobin and mean haematocrit levels regained the levels
      determined prior to the donation. Preoperative autologous blood donation of 2 to
      3 units (900-1350 ml +/- 10%) of blood is recommended in bimaxillary osteotomies
      and 1 to 2 units (450-900 ml +/- 10%) of blood for upper jaw osteotomies. In
      lower jaw surgery, the acute isovolaemic haemodilution should be considered.

PMID- 9617679
TI  - Review of case definitions for nosocomial infection--towards a consensus.
      Presentation by the Nosocomial Infection Surveillance Unit (NISU) to the Hospital
      Infection Liaison Group, subcommittee of the Federation of Infection Societies
      (FIS).
AB  - As part of the preparatory work for a national surveillance scheme, consensus was
      sought on the case definitions for nosocomial infection. We compare six sets of
      case definitions for nosocomial urinary tract infection, surgical wound
      infection, bloodstream infection and pneumonia, and highlight areas of agreement
      and variation. We hope this will stimulate discussion among those with expertise
      and interest in surveillance and so contribute to the development of nationally
      agreed case definitions.

PMID- 9617680
TI  - Selective isolation of vancomycin-resistant enterococci.
AB  - Many laboratories are likely to be or to become involved in screening patients
      for the carriage of vancomycin-resistant enterococci (VRE). A choice has to be
      made from the numerous formulations described and decisions made on the degree of
      vancomycin supplementation and the need for an enrichment phase. Few comparative
      trials and little critical evaluation has been performed to date and there is as
      yet no clear choice as to the optimal formulation. Laboratories must choose the
      formulation that most suits their particular requirements and circumstances.

PMID- 9617681
TI  - Control of an outbreak of an epidemic methicillin-resistant Staphylococcus aureus
      also resistant to mupirocin.
AB  - An epidemic methicillin-resistant Staphlococcus aureus (EMRSA-3) appeared in a
      District hospital in June 1989 as part of a regional outbreak. The dynamics of
      the outbreak were complex and involved patient transfer between hospitals and
      wards. Control measures followed UK guidelines and included the use of nasal
      mupirocin. During these efforts a mupirocin-resistant MRSA [MuMRSA: mupirocin
      minimum inhibitor concentration (MIC) > 256 mg/L] emerged, probably in a patient
      who had been given eight mupirocin courses over nine months. The MuMRSA had a
      narrower phage-typing pattern than EMRSA-3, but was indistinguishable by pulsed
      field gel electrophoresis of SmaI chromosomal restriction enzyme digests and its
      susceptibility pattern to other antibiotics. The results of in vitro curing and
      gene probing indicated that mupirocin resistance was encoded on a 48 Md plasmid.
      MuMRSA spread occurred in 12 patients and 11 staff. The affected patients were
      nursed on the same ward. The strain was eradicated from patients with oral
      ciprofloxacin and rifampicin, triclosan skin treatment and nasal fusidic acid and
      bacitracin cream. The control of the outbreak had significant medical, social and
      financial implications. Fortunately, there were alternative topical agents to
      mupirocin, an agent which has played such a key role in MRSA eradication in
      recent years.

PMID- 9617682
TI  - Infections and bacteriological data after laparoscopic and open gallbladder
      surgery.
AB  - In two hospitals 637 patients undergoing cholecystectomy between June 1989 and
      June 1993 were entered into a prospective audit. The aim of this study was to
      determine the incidence of postoperative infections, especially wound infections,
      after open and laparoscopic biliary surgery and to assess the bacteriological
      data on these patients. The incidence of minor wound infection was 10.4%
      (66/637), of major wound infection 3.6% (23/637) and the overall incidence was
      14% (89/637). The incidence of wound infection after laparoscopic cholecystectomy
      was 5.3% (10/189) and all were minor. Significant specific risk factors for
      developing a wound infection after laparoscopic cholecystectomy were emergency of
      the operation (P = 0.046) and acute cholecystitis (P = 0.014). Overall, bile
      cultures were positive in 22%. There were 85 patients (13.3%) with positive bile
      from the gallbladder. From the laparoscopically operated patients 2.8% had a
      positive bile culture. The predominant micro-organisms from gallbladder bile were
      Escherichia coli (56 isolates), Klebsiella spp. (20 isolates) and Streptococcus
      spp. (16 isolates). There was no relationship between positive gallbladder
      cultures and wound infection. The consequences of wound infections can be serious
      and this study showed a morbidity rate comparable with the literature. The
      incisions used in laparoscopic gallbladder surgery are less susceptible to major
      problems. This combined with the significantly lower incidence of wound
      infections after laparoscopic cholecystectomy suggests that routine antibiotic
      prophylaxis as recommended for biliary surgery in general is now questionable.

PMID- 9617683
TI  - The role of environmental contamination with small round structured viruses in a
      hospital outbreak investigated by reverse-transcriptase polymerase chain reaction
      assay.
AB  - In May 1994 an outbreak of vomiting and diarrhoea occurred in a 28-bed long-stay
      ward for the mentally infirm. The predominant symptoms were vomiting, diarrhoea,
      malaise and abdominal pain lasting for approximately 12 h in most cases. The
      attack rate was 62% (13/21) for patients and 46% (16/35) for staff members.
      Infection control measures were implemented (containment of infectious
      individuals, hand hygiene among staff and environmental decontamination) and the
      ward was closed to admissions. Affected staff were excluded from contact with
      patients and their food until asymptomatic for 72 h. The outbreak lasted for 17
      days. Faecal samples from nine symptomatic persons were negative for bacterial
      enteric pathogens, Giardia, Cryptosporidium and group A rotavirus. Electron
      microscopy of 12 faecal samples and one sample of vomitus revealed small round
      structured virus (SRSV) particles in one faecal sample. A further 30 faecal
      samples and seven vomitus samples were tested by reverse transcription polymerase
      chain reaction (RT-PCR) for SRSV of which 12 (40%) and 1 (14%) were positive
      respectively. Twenty-eight throat swabs from symptomatic and asymptomatic
      patients were collected, three (9.5%) of which were positive for SRSV by RT-PCR.
      Thirty-six environmental swabs were collected on the affected ward, and 11 (30%)
      were positive by RT-PCR. Positive swabs were from lockers, curtains and commodes
      and confined to the immediate environment of symptomatic patients. The
      distribution of contamination supports the rationale of cohorting sick patients.

PMID- 9617684
TI  - Yeast carriage on hands of hospital personnel working in intensive care units.
AB  - The frequency and distribution of yeast carriage on the hands of hospital
      personnel working in intensive care unit (ICUs), was investigated. Hand carriage
      of yeast and Candida species was 46 and 29%, respectively. Rhodotorula sp. and
      Candida parapsilosis were most frequently recovered. There was no significant
      difference in frequency or distribution of yeasts and Candida sp. recovered among
      the three ICUs. Seventeen C. parapsilosis isolates and three Candida albicans
      isolates were genotyped by electrophoretic karyotyping using contour-clamped
      homogenous electric-field gel electrophoresis. Eleven separate types of C.
      parapsilosis and two types of C. albicans were identified. There was no common
      genotype among these isolates, even within the same unit. We conclude that yeast
      carriage on the hands of personnel working in ICU is common, but these yeasts are
      usually not acquired from a common source in the ICU.

PMID- 9617685
TI  - Multi-resistant Pseudomonas aeruginosa outbreak associated with contaminated tap
      water in a neurosurgery intensive care unit.
AB  - From July 1995 to November 1996, multi-resistant Pseudomonas aeruginosa O11 was
      isolated from 36 patients admitted to a neurosurgery intensive care unit. The
      strain was resistant to ticarcillin, ceftazidime, imipenem, gentamicin and
      ciprofloxacin, and susceptible to amikacin. Nine patients were colonized only;
      the remaining 27 patients had at least one infected site (17 urinary infections,
      10 pneumonias and four with sinusitis). P. aeruginosa O11 with the same
      resistance pattern was isolated from tap water. The strain was also cultured from
      enteral nutrition solutions given to two infected patients. DNA macrorestriction
      analysis with XbaI established the similarity of the isolates from patients, tap
      water and solutions. The outbreak was controlled after reinforcement of isolation
      procedures for infected patients, changing the mode of enteral nutrition and
      replacement of all sinks in the unit. The sinks were presumably the main source
      of P. aeruginosa during this outbreak, via the hands of the nursing staff or
      nutrition solutions contaminated with tap water.

PMID- 9617686
TI  - Bacteria-free water for automatic washer-disinfectors: an impossible dream?
AB  - The ability of a new automatic washer-disinfector system (AWDS), fitted with a
      water filtration system to provide bacteria-free water and so avoid the risk of
      mycobacterial contamination of fibreoptic bronchoscopes, was examined. Four new
      Astec 'MP' Safescope washer-disinfectors, with coarse and fine (0.2 micron)
      filters attached close to the outlet taps, were supplied with non-softened mains
      water. Water samples from the tank supply and outlet taps were regularly assessed
      for bacterial quality over a six-month period. Outlet samples were also analysed
      after fine filter change and purgation with peracetic acid. All bronchoalveolar
      lavage specimens (BALS) were stained and cultured for mycobacteria. Only 13 out
      of 53 outlet samples (24%) were culture-negative. There was no improvement after
      filter change. Residual anti-bacterial effect of peracetic acid lasted up to 48 h
      following AWDS purgation. No tank samples were bacteria-free. Sixty BALS were
      processed, two samples were culture-positive and grew M. tuberculosis and one was
      also smear-positive. Though mycobacterial contamination of bronchoscopes was not
      evident, the water filtration system was unable to reliably provide sterile rinse
      water.

PMID- 9617687
TI  - Efficacy of specific aseptic precautions for preventing propofol-related
      infections: analysis by a quality-assurance programme using the explicit outcome
      method.
AB  - Specific aseptic precautions have been recommended for preventing infectious
      complications of propofol because its lipid base can support bacterial growth if
      contaminated. To study whether the precautions used at our institution prevent
      propofol-related infections, we retrospectively analysed the data covering 1
      January, 1995 until 30 June, 1996 held in our quality-assurance database. The
      database contains prospectively collected, detailed and standardized information
      of each patient's risk factors, anaesthetic and surgical data, and postoperative
      outcome. Surgical patients who had received propofol for anaesthesia did not have
      a higher incidence of postoperative infection, thus demonstrating the efficacy of
      our aseptic precautions.

PMID- 9617688
TI  - Risk factors for surgical site infections diagnosed after hospital discharge.
AB  - A prospective cohort study on 1103 consecutive patients undergoing general
      surgery with a follow-up of up to 30 days was undertaken to analyse the risk
      factors for surgical-site infection (SSI). Relative risks (RRs), crude and
      multiple-risk factors adjusted for by logistic regression analysis, and their 95%
      confidence intervals were calculated. One hundred and four patients (9.4%)
      developed infection, 81 in hospital and 23 at home. Predictors for in-hospital
      SSI differed from those for post-discharge SSI. In a crude analysis, an increased
      risk of post-discharge SSI occurred after clean-contaminated surgery (but not
      contaminated surgery). Stepwise logistic regression failed to identify any
      significant predictor for post-discharge SSI.

PMID- 9617689
TI  - Guidelines for the management of patients colonized or infected with vancomycin
      resistant enterococci.

PMID- 9617690
TI  - Nosocomial diskitis due to Propionibacterium acnes.

PMID- 9617691
TI  - Increased incidence of Clostridium difficile infection.

PMID- 9617692
TI  - Why, when and how to clean stethoscopes.

PMID- 9617693
TI  - Lionel Sharples Penrose (1898-1972): aspects of the man and his works, with
      particular reference to his undertakings in the fields of intellectual disability
      and mental disorder.
AB  - The Penrose Club, named after Professor L. S. Penrose, is a society of academic
      psychiatrists in the UK with a particular focus on research in the sphere of
      intellectual disability. The inaugural lecture of the Club was delivered at the
      Institute of Psychiatry, London, on 29 November 1996. It is distinctly fitting
      that this lecture should appear in print in the Journal of Intellectual
      Disability Research in the centenary year of Professor Penrose's birth, both
      because of his major pioneering contributions to the field with which JIDR is
      concerned and because he played a crucial role in the founding of the Journal.

PMID- 9617694
TI  - A longitudinal study of the quality of life of older people with intellectual
      disability after leaving hospital.
AB  - A study was made of the quality of life of 29 older people with intellectual
      disability who left hospital to live in ordinary three- or four-bedroom houses. A
      short version of the Questionnaire on Quality of Life was used to measure quality
      of life before moving and at three points in the first 53 months after changing
      residence. Results showed that there were improvements in quality-of-life
      subscales in the first 41 months with an eventual levelling out after 53 months.
      Social and leisure activity have been identified as particular important in the
      quality of life of older people. Therefore, items from the scale that measure
      participation in community leisure activities, contact with people without
      intellectual disability during these activities and engagement in leisure
      activities within the home were selected for detailed analysis. These data also
      showed increased activity and contacts in the first 41 months with a levelling
      out after 53 months.

PMID- 9617695
TI  - The nature of leisure in the lives of older adults with intellectual disability.
AB  - The purpose of this study was to examine the nature of leisure in a sample of
      older adults with intellectual disability. Twenty-nine older adults participated
      in indepth interviews. An interview guide was utilized which included topics
      relating to leisure participation and social interaction in a variety of
      environments. Data were analysed according to the constant comparative method.
      The most pronounced theme that emerged from the data was lack of self
      determination in leisure. Participants had few opportunities to freely choose
      leisure in any aspect of their lives. In many cases, opportunities for self
      determined leisure were further constricted by age-related changes in the
      participants' lives.

PMID- 9617696
TI  - A five-year follow-up study of older long-stay clients with intellectual
      disability using the Disability Assessment Schedule.
AB  - The emphasis on community care means closure of the long-stay institutions for
      people with intellectual disability. Studies have indicated that older people
      with intellectual disability in particular may not be adequately cared for
      because of poor monitoring of their changing needs and inadequate provision of
      services. The use of rating instruments to monitor changes, and to predict
      outcome or needs in this population may help to improve care by assisting with
      planning and projection of service requirements. In 1991, all residents of a long
      stay hospital for people with intellectual disability were assessed using the
      Disability Assessment Schedule (DAS). Five years later, the 1991 scores of the
      older residents (aged > 50 years) were reviewed and compared under three outcome
      groups: in-patients, discharged and deceased. Furthermore, all older people
      resident in the hospital in 1996 were reassessed using the DAS. Out of the 144
      older clients resident in 1991, five years later, 78 were still in-patients, 38
      had been discharged into the community and 28 were deceased. In 1991, the
      decreased group had the greatest problems with continence and symbolic behaviour,
      while the discharged group had the greatest problems with self-help, vision,
      hearing, communication, social interaction, echolalia and repetitive speech. In
      comparison with 1991, the 1996 DAS scores of older residents showed that there
      were increasing problems with vision, hearing, communication, behaviour and
      symbolic activities. The present study suggested that the DAS is a useful
      instrument for monitoring change and predicting outcome in older people with
      intellectual disability.

PMID- 9617697
TI  - An epidemiological and aetiological study of children with intellectual
      disability in Taiwan.
AB  - A large-scale cytogenetic study of the causes of intellectual disability (ID) in
      children from special schools and institutions was made in Taiwan between 1991
      and 1996. The screening methods and the identification of subjects with ID
      consisted of both clinical evaluation (i.e. photographs, questionnaires on
      family, pre-, peri- and postnatal history, and hospital records, including IQ)
      and further laboratory studies for diagnosis (i.e. standard chromosome analysis,
      and if indicated, high-resolution banding, cytogenetic fragile-X study or
      molecular techniques). A total of 11,892 patients were enrolled in this study.
      After excluding the acquired causes of ID, such as infections and the sequelae of
      brain insults, or the well-known single-gene disorders and other multifactorial
      diseases, 4372 (36.8%) cumulative cases were recruited for karyotyping studies
      according to their phenotypes and medical records. Abnormal karyotypes were noted
      in 1889 children (43.2% of all selected children). Thus, the overall incidence of
      chromosomal aberrations in subjects with ID was estimated as 15.9%. Down's
      syndrome, the most common cause of ID, accounted for 82.4% of all patients with
      abnormal karyotypes. The causes of ID were considered to be prenatal in 55.2% (n
      = 6564) of cases, perinatal in 9.5% (n = 1130), postnatal in 3.3% (n = 392) and
      unknown in 32.0% (n = 3805) of cases. Two large groups were classified: (1)
      serious ID (37%), including profound, severe and moderate categories; and (2)
      mild ID (63%). The causes (pre-, peri- and postnatal, and unknown) in these two
      populations were: 70%, 10.5%, 5.4% and 14.1%, and 46.5%, 8.9%, 2.1% and 42.5%,
      respectively. Genetic causes accounted for 38.5% (n = 4578) of all cases in this
      study, including 1557 with Down's syndrome, 233 with fragile-X syndrome, 199 with
      other various chromosomal abnormalities (i.e. unbalanced translocation,
      supernumerary markers and structural rearrangements), 238 with a defined or
      presumed single-gene defect, and 98 with a recognized contiguous gene syndrome
      (Prader-Willi, 56; Angelman, 34; Williams, 5; and Kallmann, 3); 2120 cases had
      familial ID. Multiple anomalies of undefined pattern, but without chromosomal
      aberration, infantile autism, ID of normal phenotype or family history, were of
      the other categories. Patients with a single-gene disorder or chromosomal
      aberration, especially those with unbalanced translocated or rearranged
      chromosomes, had genetic counselling and family studies. Pre-screening with
      photographs and questionnaires may give a better costbenefit than blind mass
      cytogenetic studies for each individual with ID.

PMID- 9617698
TI  - Time demands and experienced stress in Greek mothers of children with Down's
      syndrome.
AB  - The purpose of the present study was to asses the time demands placed on mothers
      of children with Down's syndrome, and the possible relationship between those
      demands and the stress which the mothers experience. The study sample consisted
      of 41 mothers of children with Down's syndrome living in Northern Greece and a
      comparison group of 41 mothers of non-disabled children. Three instruments were
      used for the data collection: (1) a questionnaire for biographic information; (2)
      a self-report form assessing the time demands placed on the mothers; and (3) an
      adaptation of the Clark Questionnaire on Resources and Stress (QRS) for the
      evaluation of the stress experienced. The results of the present study revealed
      increased time demands on the mothers of children with Down's syndrome in
      comparison to the mothers of non-disabled children in terms of
      recreational/educational activities and total time demands. Furthermore, the
      mothers of children with Down's syndrome perceived the time they spend with their
      children less positively than the mothers of the comparison group. In regard to
      the stress experienced, it appeared that mothers of children with Down's syndrome
      differ significantly from mothers of non-disabled children, not only on the level
      of the stress which they experience, but on the activities related to this stress
      as well.

PMID- 9617699
TI  - A questionnaire survey of sleep and night-time behaviour in a community-based
      sample of adults with intellectual disability.
AB  - Two hundred and five people with intellectual disability, aged 18 years or over,
      and living in health- or social-services-managed community housing, completed
      sleep and behaviour questionnaires. An 85.7% return rate was achieved. Settling
      problems were present in 26.8% and night waking in 55.6% of the subjects.
      Parasomnias were present in 14% of subjects and 15% of the sample showed some
      features associated with sleep-related breathing problems. Factors associated
      with sleep-related problems included gender, aetiology of intellectual
      disability, epilepsy, treatment with antiepileptic medication, evening caffeine
      consumption, nocturnal urinary incontinence and ability to communicate.
      Significant sleep-related problems were demonstrated in this population; some of
      these problems might be avoided by simple measures.

PMID- 9617700
TI  - Investigating the relationship between stress and worker behaviour.
AB  - Direct care staff working in six residential group homes for people with
      intellectual disability were asked to complete a questionnaire which asked for
      information on levels of stress (anxiety and depression), the types of demand
      experienced by the staff, the support they received and the constraints they
      faced at work. Staff were also observed at work using a schedule which detailed
      who they interacted with, the content and type of interaction, and what
      activities staff were involved in. Measurement of workers' anxiety and depression
      levels confirmed management assessments of staff stress levels in the homes: two
      residential group homes were classified as 'low stress' and four as 'high
      stress'. A number of differences emerged between the two groups. Staff in the
      high stress homes reported greater demands and less support than those in the low
      stress homes. Higher levels of interaction were found between staff and residents
      in low stress houses, where more of the interaction was given as assistance and
      positive interactions. However, activities in higher-stress group homes appeared
      to be more community oriented, with staff spending a much greater amount of time
      out of the house. The importance of these results for both staff and residents is
      discussed, and suggestions for further work are made.

PMID- 9617701
TI  - Reliability and validity of the PAS-ADD Checklist for detecting psychiatric
      disorders in adults with intellectual disability.
AB  - The PAS-ADD Checklist is a screening instrument specifically designed to help
      staff recognize mental health problems in the people with intellectual disability
      for whom they care, and to make informed referral decisions. The instrument
      consists of a life-events checklist and 29 symptom items scored on a four-point
      scale. Scores are combined to provide three threshold scores. The crossing of any
      of these thresholds indicates the need for a fuller assessment. The items are
      worded in everyday language, making the Checklist suitable for use by individuals
      who do not have a background in psychopathology. The present paper presents the
      results of a number of studies evaluating the reliability and validity of the
      Checklist. Factor analysis of Checklists completed on a community sample of 201
      individuals yielded eight factors, of which seven were readily interpretable in
      diagnostic terms. Internal consistency of the scales was generally acceptable.
      Inter-rater reliability in respect to individual items gave a fairly low average
      Kappa of 0.42. However, agreement on case identification, the main purpose of the
      Checklist, was quite good, with 83% of the decision being in agreement. Validity
      in relation to clinical opinion was also satisfactory, case detection rising
      appropriately with the clinically judged severity of disorder. The PAS-ADD
      Checklist is published and distributed by the Hester Adrian Research Centre,
      Manchester, England, from where further information and order forms are available
      on request.

PMID- 9617702
TI  - Velo-cardio-facial syndrome, schizophrenia and deletion at chromosome 22q11.
AB  - A man with intellectual disability presented with schizophrenia, hypocalcaemia,
      facial dysmorphism and cleft soft palate. Velo-cardio-facial syndrome was
      diagnosed and deletion at 22q11 was confirmed by fluorescent in situ
      hybridization.

PMID- 9617703
TI  - Balancing restriction and freedom in the care of people with intellectual
      disability.
AB  - The case of a 50-year-old man with severe intellectual disability is described.
      After 20 years of institutional care, the subject was moved to a newly opened
      community group home. His physical and mental health deteriorated at this
      location after unproven allegations of sexual abuse which had taken place whilst
      he had been living in the institution. Although the subject's health continued to
      deteriorate, there was resistance to his readmission to the same hospital for
      assessment. He had always needed to be cajoled into eating, but this approach had
      not been followed by the home which had contributed towards his weight loss. The
      situation the subject, the carers and the health personnel found themselves in
      illustrates how problematic it is to find the right balance between restrictive
      practices and respect for an individual's choice.

PMID- 9617704
TI  - Neuroborreliosis.
AB  - Neuroborreliosis, a manifestation of infection with the spirochete Borellia
      burgdorferi, has become the most frequently recognised arthropod-borne infection
      of the nervous system in Europe and the USA. The best criterion of an early
      infection with B. burgdorferi is erythema migrans (EM), but this is present in
      only about 40-60% of patients with validated borreliosis. Therefore use of the
      duration of the disease as a classification criterion for neuroborreliosis is
      increasing, the chronic form being distinguished from the acute when symptoms
      persist for more than 6 months. The diverse manifestations of neuroborreliosis
      require that it be included in the differential diagnosis of many neurological
      disorders. In Europe, meningopolyradiculoneuritis (Bannwarth's syndrome)
      represents the most common manifestation of acute neuroborreliosis, with the
      facial nerve being affected much more frequently than the other cranial nerves.
      Clinical symptoms affecting the central nervous system are rarely observed and
      then mostly in chronic courses. By far the most common manifestation of chronic
      neuroborreliosis is encephalomyelitis with spastic-ataxic disturbances and a
      disturbance of micturition. The current diagnosis of neuroborreliosis is a
      clinical one, which has to be confirmed by laboratory testing. In most patients,
      examination of the cerebrospinal fluid (CSF) reveals lymphocytic pleocytosis,
      damage to the blood-CSF-barrier and an intrathecal synthesis immunoglobulin (Ig)
      M, IgG, and sometimes IgA. Confirmation of a borrelial infection of the nervous
      system requires demonstration of an intrathecal synthesis of borrelial-specific
      antibodies in the CSF or detection of borrelial DNA in the CSF by polymerase
      chain reaction (PCR). There is no generally accepted therapeutic regime for the
      treatment of neuroborreliosis, but recent studies have shown ceftriaxone 2 g/day
      and cefotaxime 6 g/day to be effective in acute and chronic courses. Penicillin G
      20 mega units/day and doxycycline 200 mg/day may be suitable for uncomplicated
      meningopolyneuritis, without involvement of the central nervous system. The
      durationof treatment--at least 2 weeks in the acute forms and 3 weeks in the
      chronic forms of neuroborreliosis--is very important for successful treatment.
      Corticosteroids are recommended only for patients with severe pain that does not
      respond to antibiotics an analgesics.

PMID- 9617705
TI  - Effects of sex, height and age on motor evoked potentials with magnetic
      stimulation.
AB  - Magnetic stimulation of the brain and cervical and lumbar spinal roots was
      performed on 48 healthy subjects in order to investigate the effects of sex,
      height and age on motor evoked potentials (MEPs). The compound muscle action
      potentials were recorded from the abductor pollicis brevis and abductor hallucis
      muscles. The central motor conduction time (CMCT) was measured between the
      cerebral cortex and the cervical root and also between the cerebral cortex and
      the lumbar root. A multiple regression analysis was used to determine which of
      the physical variables, namely sex, height and age, were significant. A
      significant gender difference was observed in the MEP latencies and CMCT of the
      leg, but not in those of the hand. Both height and age had a significant effect
      on the leg MEP latencies with a lesser effect on the hand MEP latencies. The leg
      CMCT was also significantly influenced by height and age, while the hand CMCT was
      not. These results thus suggest that physical variables are very important in
      defining normal MEPs, especially in the lower limbs. Therefore, when we assess
      motor function in patients with neurological disorders, both the patients and
      control groups should be matched for sex, height and age distribution.

PMID- 9617706
TI  - Stages and syndromes of neuroborreliosis.
AB  - To ascertain the varieties of neuroborreliosis, 330 patients were identified at
      the Departments of Neurology in Wurzburg and Giessen from 1979 to 1994. Patients
      who fullfilled at least one of three strict case definitions based on clinical
      and laboratory criteria were included in the study. Ninety-one per cent of the
      patients had second-stage neuroborreliosis (duration of symptoms < or = 6
      months). The most common syndrome was a painful spinal meningoradiculitis, alone
      (37%) or in combination with a cranial radiculitis (29%). Meningoradiculitis
      cranialis (9%), isolated meningitis (4%) and erythema chronica migrans-associated
      mono/polyneuritis (3%) were further stage II features. Central nervous system
      involvement occurred either as an acute meningomyelitis or
      meningomyeloradiculitis (5%) and meningoencephalitis or
      meningenocephaloradiculitis (4%). Less than 9% of the patients ran a chronic
      course (stage III) with a disease duration between 6 months and 9 years, either
      as acrodermatitis chronica atrophicans associated mono- or polyneuritis (2%) or a
      chronic progressive encephalomyelitis (6%). Cerebrovascular neuroborreliosis (1%)
      occurred in both stages; however, the primary nature of the course was a chronic
      one. Involvement of other organs except the skin was rare (joints 3%, heart 1%)
      but elevated hepatic enzymes were frequent. Our study demonstrates that
      neuroborreliosis has to be considered in the differential diagnosis of a wide
      variety of neurological conditions. Cerebrospinal fluid analysis and the search
      for specific intrathecal antibody production are important diagnostic procedures.

PMID- 9617707
TI  - The effect of repositioning on brain MRI lesion load assessment in multiple
      sclerosis: reliability of subjective quality criteria.
AB  - The aim of this study was to assess the variability of lesion load measurements
      for repeated brain magnetic resonance imaging (MRI) scans judged to have either
      poor or good repositioning quality on the basis of subjective criteria used for
      clinical trials in multiple sclerosis (MS). Scan-rescan variability was also
      compared with the intra-observer variability assessed from three repeated volume
      measurements of the same scan. Nine patients with MS were studied; each of them
      underwent the scan-rescan procedure on the same day. Five scans were considered
      to have poor and four scans to have good repositioning. Between these two groups
      there were no differences in either the mean lesion loads or the measurement
      variance. For the whole group of patients, the intra-observer variability of
      repeated measurements gave a significantly lower coefficient of variation (COV =
      4.9%) than the variability owing to repositioning (COV = 8.9%, P < 0.01, F test).
      Our results confirm that the effect of repositioning on brain MRI lesion load
      assessment is stronger than that owing to the intra-observer variability for
      repeated measurements and indicate that the simple visual judgment about the scan
      repositioning quality seems unable to predict the scan-rescan reproducibility.

PMID- 9617708
TI  - Venous transcranial Doppler in acute dural sinus thrombosis.
AB  - The value of conventional transcranial Doppler ultrasound in the diagnosis and
      monitoring of cerebral vein thrombosis is unclear. Previous studies have
      suggested the usefulness of this method in two cases with superior sagittal sinus
      thrombosis that showed increased velocities of deep cerebral veins. The purpose
      of the present study was to evaluate the deep intracranial venous circulation in
      patients with that pathology. Venous transcranial Doppler ultrasound was
      performed with a range-gated 2 MHz transducer in 17 healthy volunteers and in six
      cases of proven acute superior sagittal sinus thrombosis. Peak systolic, end
      diastolic and mean blood flow velocities were measured in the basal vein of
      Rosenthal (BVR) and deep middle cerebral vein (DMCV) through a posterior temporal
      window. In 16 controls and in one patient, the straight sinus was also studied
      through an occipital approach. Sex distribution and mean age of controls and
      patients were similar. Mean blood flow velocities in controls were as follows
      (mean, SD): DMCV, 10.4, 1.4 cm/s; BVR, 11.3, 1.8 cm/s; straight sinus, 29.5, 9.9
      cm/s. Three of the patients with superior sagittal sinus thrombosis showed
      increased velocities either in the DMCV, the BVR or the straight sinus. One
      patient showed slightly increased velocities in the BVR, and the other two showed
      normal venous velocity values. This study confirms the usefulness of conventional
      transcranial Doppler ultrasound in detecting superior sagittal sinus thrombosis.
      However, a normal examination does not exclude this diagnosis.

PMID- 9617709
TI  - Callosal and corticospinal tract function in patients with hydrocephalus: a
      morphometric and transcranial magnetic stimulation study.
AB  - In 15 patients with symptomatic hydrocephalus, pressure-induced morphological
      changes of the brain and the function of callosal and corticospinal fibres were
      studied. Morphometry of the corpus callosum (CC) was performed on midsagittal MR
      images. Focal transcranial magnetic stimulation of the motor cortex was used to
      assess simultaneously excitatory motor responses in contralateral hand muscle
      (corticospinally mediated effect) and inhibition of tonic EMG activity in
      ipsilateral hand muscles (transcallosal inhibition (TI) of the contralateral
      motor cortex). Before a shunt operation, the midsagittal area of the CC was
      reduced by 34% on average. The height and, to a lesser degree the length, of the
      CC were increased before the shunt operation. Thresholds and central motor
      latencies of corticospinally mediated responses were normal, response amplitudes
      were smaller than in normal subjects. Motor thresholds increased from 38, SD 5 to
      52, SD 8% (P < 0.01) within 7 days after ventricular drainage, reflecting the
      increase in the distance between stimulation coil and brain. The threshold
      increase paralleled a restoration of normal anatomical conditions within 7 days
      after shunt operation and the improvement of motor symptoms and might be a
      predictor of successful decompression. Transcallosal inhibition could be elicited
      in all patients. The measurements of TI lay within the normal range except the
      duration, which was prolonged in 73% of 15 patients before shunt operation as a
      probable indicator of an increased dispersion of callosal conduction. The
      normalization of the area and shape of the CC after shunt operation and the
      normal corticospinal and callosal conduction times exclude degeneration,
      demyelination or functional block of a large proportion of callosal or
      corticospinal tract fibres or a substantial loss of nerve cells in motor cortex.

PMID- 9617710
TI  - A new non-radioactive method for the screening and prenatal diagnosis of myotonic
      dystrophy patients.
AB  - Myotonic dystrophy (DM) is an autosomal dominant neuromuscular disease with an
      estimated incidence of 1 in 8000 and is the most common form of muscular
      dystrophy affecting adults. An unstable, untranslated part of the myotonic
      dystrophy protein kinase gene on the long arm of chromosome 19, composed of CTG
      repeats, is a genetic marker for DM. We have developed a fast non-radioactive
      polymerase chain reaction (PCR) procedure to detect the (CTG)n repeat expansion
      in DM patients and their relatives. Genomic DNA extracted from peripheral blood
      lymphocytes was amplified by PCR using specific primers to flank the region
      containing the triplets. To improve the amplification of this CG-rich region,
      either 10% glycerol or rTth DNA polymerase XL (extra long) was added to the
      reaction mixture, allowing amplification of huge expansions otherwise not
      polymerized by PCR. The PCR products were Southern blotted and the expansion
      revealed using a fluorescein-labelled (CTG)10 probe. We compared our results with
      those obtained in 24 patients and relatives using genomic digestion followed by
      radioactive Southern blot; in all cases the results overlapped. The same
      technique was used for prenatal diagnosis in pregnant DM mothers. We conclude
      that this new method is reliable for the genetic testing of DM patients.

PMID- 9617711
TI  - The sensory innervation pattern of the fingers.
AB  - In 32 subjects without signs or symptoms of peripheral nerve disorder, sensory
      nerve action potentials (SNAPs), elicited by stimulation at the wrist, were
      recorded from the fingers of both hands with ring electrodes. Recordings from the
      volar proper digital nerves confirmed the standard distribution of the median and
      ulnar cutaneous innervation. Recordings from the dorsal digital nerves, however,
      showed that the contribution of the dorsal cutaneous branch of the ulnar nerve
      (DCUN) strongly decreases from the little finger (always a SNAP) to the middle
      finger (rarely a SNAP), and that the contribution of the radial nerve decreases
      in an identical way from the thumb to the middle finger. Anatomical studies have
      shown that small branches from the DCUN and the radial nerve contribute to the
      innervation of the dorsal aspect of the proximal part of the middle finger, but
      it seems likely from our data that the predominant innervation of this area is
      usually provided by the median nerve. Furthermore, we found that the dorsal
      aspect of the proximal part of the ring finger is mainly supplied by the DCUN.
      These findings differ from the standard cutaneous innervation pattern as depicted
      in neurological textbooks, but they are in agreement with earlier anatomical
      studies.

PMID- 9617712
TI  - Orthostatic tremor associated with cerebellar ataxia.

PMID- 9617713
TI  - A case of ethambutol-induced optic neuropathy harbouring the primary
      mitochondrial LHON mutation at nt 11778.

PMID- 9617714
TI  - An introduction to the concept of "quality of life in Parkinson's disease".
AB  - The sense of well-being is central to the concept of quality of life (QoL), but
      there is not a universally accepted definition of health-related QoL. QoL refers
      to the patient's own evaluation of the impact of the disease. It includes
      physical, psychological and socioeconomic dimension, and its measurement is of
      paramount importance in evaluating research outcomes and in cost-benefit
      analyses. In addition, QoL assessment helps to identify problems and may be
      essential in chronic and disabling diseases such as in Parkinson's disease (PD).
      There are numerous reasons for the decrease in QoL suffered by PD patients:
      restrictions in mobility, falls, emotional disorders, social embarrassment,
      isolation, sleep disturbances, dyskinesias, and fluctuations. Many aspects of
      these disorders go unnoticed in clinical evaluation, and only QoL assessment
      allows them to be rated. Generic instruments have been used in a few studies
      measuring QoL in PD patients. Only recently have specific instruments as PDQ-39
      and PDQL-37 been designed and validated. QoL assessment in PD is an important and
      expanding area, with a promising application in clinical trials and
      pharmacoeconomics.

PMID- 9617715
TI  - From the moment of diagnosis.
AB  - The population is living longer today, and with old age comes frailty and more
      long-term neurological illnesses. Parkinson's disease will become more common,
      and to support community care better, funds will need to be shifted to this
      sector. There are a number of Parkinson's disease societies in Europe, and a
      working group on this disease will be meeting in Geneva in May 1998. This is
      therefore a time for closer collaboration with many organisations, which will
      result in increased awareness and thereby an improvement in quality of life.

PMID- 9617716
TI  - PDQ-39: a review of the development, validation and application of a Parkinson's
      disease quality of life questionnaire and its associated measures.
AB  - Parkinson's disease is a common degenerative neurological condition. A number of
      general instruments exist to measure quality of life, but these were not designed
      to address areas salient to a specific disease. This contribution reviews the
      development and validation of the PDQ-39, a short 39-item quality of life
      questionnaire for Parkinson's disease. PDQ-39 data can be presented either in
      profile form or as a single index. This report also reviews the development and
      validation of a briefer measure (PDQ-8) derived from the PDQ-39, and of two
      summary indices (PDQ-39SI and PDQ-8SI.

PMID- 9617717
TI  - Sleep disorders in Parkinson's disease.
AB  - The nature of sleep is one of the major sources of dissatisfaction with the
      quality of life among patients with Parkinson's disease (PD). Difficult sleep
      maintenance (light and fragmented sleep) and difficulties with sleep initiation
      are the earliest and most frequent sleep disorders observed in these patients.
      Sleep disorders are also common in the normal elderly population, suggesting that
      normal aging may play a role in the etiology of sleep disorders in PD. Factor et
      al. examined the frequency of various sleep disorders in PD and compared them to
      those of normal elderly subjects. Sleep fragmentation and spontaneous daytime
      dozing occurred much more frequently in PD patients than in controls. Sleep
      fragmentation in PD may be due to an increased skeletal muscle activity,
      disturbed breathing and REM/non-REM variations of the dopaminergic receptor
      sensitivity. In parkinsonian patients who developed motor fluctuations (on-off
      phenomenon, wearing-off) during the day, other common sleep-related motor
      complaints including nocturnal akinesia, dystonia and painful cramps are
      observed. In a double-blind cross-over study, we compared the efficacy of a
      single dose of a chronic release formulation of levodopa/carbidopa (Sinemet CR)
      with that of a placebo in improving sleep-related motor disturbances in a group
      of 40 fluctuating PD patients. Sinemet CR significantly improved nocturnal
      akinesia and increased the hours of sleep in this group of patients. Initiation
      and maintenance of sleep are problems that may not be solved with
      antiparkinsonian treatment.

PMID- 9617718
TI  - Practical approach to quality of life in Parkinson's disease: the nurse's role.
AB  - In recent years it has become apparent that nurses have several key roles in the
      treatment of Parkinson's disease. These include the practice of skilled clinical
      care, the provision of advice and education, communicating with patients and
      carers, and also between health and social care agencies. Their goals are to
      facilitate good clinical care, to reduce morbidity (both physical and
      psychological) and to achieve better informed patients by the reduction of
      misinformation, fear and distress caused by the diagnosis and consequences of
      this disease. The overall goal is to improve the prognosis and to reduce the
      impact of this disease on patients and their care givers. To achieve these goals
      the specialist nurse needs skills in assessment, reassessment and counselling in
      addition to knowledge of the disease and its management. The training needs have
      been established for the nursing profession to address these issues, and courses
      have been established and approved. A scale comprising four clinical management
      stages has been proposed: initially around the time of diagnosis; stable
      maintenance therapy; a more complex management stage, and palliative care.
      Nursing interventions and priorities differ in these arbitrary stages. Several
      models of nursing provision have been piloted in the United Kingdom, and results
      of evaluations are keenly awaited. Meanwhile, specialist nurses are proving to be
      popular with patients and carers, medical specialists, and the Parkinson's
      Disease Society which aims to see their provision in each Health District
      throughout the United Kingdom. In summary, the nursing role is complementary to
      those of the other members of the multi-disciplinary health team that aims to
      improve the quality of life of PD patients and their carers.

PMID- 9617719
TI  - Additional therapies in Parkinson's disease patients: useful tools for the
      improvement of the quality of life or senseless loss of resources?
AB  - In advanced stages of Parkinson's disease problems of speech, mobility and
      balance occur with a high frequency. Although the symptoms of the disease can be
      treated by specific and individual pharmacotherapy, some of the severe symptoms
      such as freezing, falls, unsteadiness, and dysarthria persist. To evaluate the
      potential use of additional therapies, a diagnosis of all current symptoms must
      be performed; afterwards a specific individual treatment can be decided by the
      therapist based on objective data. Only if the initial evaluations of a new
      therapy show improvement, will such therapies be subjected to long-term
      evaluation, which should be also performed by the patient. This contribution
      presents examples of a useful prediagnosis and of the evaluation of the
      conventional physiotherapy. Also, two new methods are evaluated as additional
      therapies: low-frequency muscle stimulation and magnetic pulse therapy. A
      thorough symptomatic diagnostic view, specifically directed additional therapy
      and the careful evaluation of the use of therapies provide the only meaningful
      treatment of Parkinson's disease.

PMID- 9617720
TI  - Quality of life and Parkinson's disease: the CR FIRST Study.
AB  - Quality of life is an important issue in the treatment of Parkinson's disease.
      Both general and disease specific quality of life scales are now being used in
      interventional trials. In the Sinemet CR First trial, the long-acting preparation
      was found to be superior to the immediate release preparation in several measures
      of the Nottingham Health Profile, a generic quality of life scale. In particular
      social isolation and emotional reactivity was better with Sinemet CR. The long
      acting drug was also superior for all five years of the study, for activities of
      daily living subscale of the UPDRS. It is concluded the Sinemet CR may have
      advantages over the immediate release preparation on Quality of life issues in
      PD.

PMID- 9617721
TI  - Quality of life in patients with Parkinson's disease who transfer from standard
      levodopa to Sinemet CR: the STAR Study. The STAR Multicenter Study Group.
AB  - Conversion from standard levodopa to Sinemet CR was performed in a series of 450
      patients with Parkinson's disease. Of these, 299 experienced motor complications
      (group A) and 151 showed stable motor response (group B). There was significant
      improvement in various parameters of efficacy (Unified Parkinson's Disease Rating
      Scale, Hoehn-Yahr staging, Schwab-England scale) particularly in those related to
      functional aspects such as activities of daily living of the Unified Parkinson's
      Disease Rating Scale, sleep questionnaires and the Nottingham Health Profile.
      Adverse effects were usually mild or moderate, and only 10% of patients
      discontinued Sinemet CR due to side effects. Sinemet CR treatment was preferred
      by 81% of patients in group A and by 73.8% of patients in group B.

PMID- 9617722
TI  - Quality of life in Parkinson's disease: validation study of the PDQ-39 Spanish
      version. The Grupo Centro for Study of Movement Disorders.
AB  - The present multicenter study evaluated the validity of the PDQ-39 Spanish
      version (PDQ-39 SV) for assessing health-related quality of life (QoL) in
      Parkinson's disease (PD). A total of 103 PD patients were evaluated by the Hoehn
      and Yahr stage and by the following scales: Unified Parkinson's Disease Rating
      Scale (UPDRS), Schwab and England scale, Pfeiffer's SPMSQ, and Geriatric
      Depression Scale. The Hospital Anxiety and Depression Scale and the PDQ-39 SV
      were self-completed by patients. For analysis of data we used descriptive
      statistics, Cronbach's alpha, Spearman's rank correlation coefficients, and the
      Kruskal-Wallis test. The internal consistency of the PDQ-39 SV dimensions was
      satisfactory (Cronbach's alpha: 0.63-0.94; item-total correlation: 0.57-0.87, P <
      0.001), although Social Support and Cognition items were beneath ideal values.
      Recorded results for Mobility, Activities of Daily Living, and Communication were
      highly correlated with PD rating scales (rs = 0.49-0.73, P < 0.001). Emotional
      Well-Being and Body Pain showed their best correlations with mood measures.
      Cognition was the only dimension significantly correlated with the SPMSQ (RS =
      0.27, P < 0.01). These data and previous studies indicate that the PDQ-39 is a
      consistent instrument for evaluation of physical, emotional, and psychosocial
      aspects of QoL in PD patients.

PMID- 9617723
TI  - Scale of Quality of Life of Care-Givers (SQLC).
AB  - There is growing interest today in the design and application of tools for
      measuring quality of life. However, the rating scales applied do not reveal the
      consequences that Parkinson's disease has for patients' relatives. The need for
      permanent care and help to be given to the chronically disabled person leads to a
      decrease in the life quality of caregivers. The contribution describes an
      inventory for evaluating the quality of life of parkinsonian patients' caregivers
      and analyses some factors determining their social disadaptation.

PMID- 9617724
TI  - Relationship between muscle fiber composition and functional capacity of back
      muscles in healthy subjects and patients with back pain.
AB  - Back muscles are important to the stability of the lumbar spine. Muscle fiber
      composition may give some indication of the functional capacity of these muscles.
      This review explores the relationship between muscle fiber composition and
      functional capacity of back muscles. The reference values for the type and size
      of the muscle fibers found in the back musculature of healthy subjects and
      patients with back pain are also presented. A high percentage of type I fibers,
      which are larger in size than type II fibers, has been found in back muscles at
      the thoracic and lumbar levels. This is in accordance with the postural function
      of these muscles. The diameter of type II fibers is smaller in females than
      males, which may partly explain the lesser strength and greater endurance
      capacity of back muscles in females. Due to the limited amount of pertinent data,
      no conclusive evidence is available regarding age-related changes in muscle fiber
      composition in the musculature of the back. In patients with lumbar disorders,
      pathological changes and selective atrophy of type II fibers are seen, and these
      can be changed with adequate exercises. Further research is suggested to address
      issues related to gender, age, back pain, and exercise and their effects on the
      apparent back muscle fiber composition.

PMID- 9617725
TI  - Effects of cold and compression dressings on early postoperative outcomes for the
      arthroscopic anterior cruciate ligament reconstruction patient.
AB  - Efforts to minimize the morbidity of anterior cruciate ligament (ACL)
      reconstruction include the use of cryotherapy and/or compressive dressings in the
      immediate postoperative period. We undertook the present study to determine if
      the alleged benefits of the Cryo/Cuff, which combines these modalities, are more
      attributable to its compressive effect rather than cold application. Seventy
      eight patients admitted for primary endoscopic ACL reconstruction using a bone
      patella tendon-bone autograft were randomized to receive Cryo/Cuff compressive
      dressings postoperatively. Forty subjects (Group 1) had the cuff applied with
      continuous circulating ice water using the Autochill device, while 38 others
      (Group 2) received the cuff with room temperature water. Cases were performed as
      inpatients and all subjects were administered intravenous morphine
      postoperatively via a patient-controlled infusion pump for the first 24
      postoperative hours. At baseline, the groups were well matched in age, sex,
      duration of symptoms, operative time, and associated meniscal surgery. No
      significant difference between groups was detected with respect to length of
      hospitalization, Hemovac knee drainage, oral and intravenous narcotic
      requirement, or subjective pain as measured by a visual analog scale. No apparent
      complications related to the use of the Cryo/Cuff dressings were noted. The
      clinical effect of the Cryo/Cuff in this study was not influenced by the use of
      continuous ice water vs. room temperature water. Further study should focus on
      variations in compression to evaluate the clinical impact of this device.

PMID- 9617726
TI  - Preoperative indicators of motion loss and weakness following anterior cruciate
      ligament reconstruction.
AB  - Loss of motion and knee extension weakness are recognized as significant
      complications following anterior cruciate ligament (ACL) reconstruction. The
      purpose of this study was to determine 1) what degree of preoperative motion loss
      represents a risk for postoperative motion problems and 2) if preoperative
      weakness (deficit > or = 20%) affects return of strength following surgery.
      Measurements of range of motion and strength were made on 102 patients (56 men,
      46 women; age = 31 +/- 1 years) within 2 weeks prior to ACL reconstruction
      (preop) and repeated 6 months following surgery (postop). Thirteen of 40 patients
      (33%) lacking > or = 5 degrees preop, eight of 20 patients (40%) lacking 1-4
      degrees preop, and three of 42 (7%) patients with full extension preop had > or =
      5 degrees loss 6 months postop (p < 0.001). Thirty-two of 39 (82%) patients with
      normal strength preop had weakness 6 months postop. Forty of 51 (78%) patients
      with preop knee extension weakness still had weakness 6 months postop. Preop
      strength was not a good predictor of residual weakness following ACL
      reconstruction. The magnitude of the preop extension loss appears not to be a
      risk factor. It is the presence or absence of full extension equal to the
      contralateral leg that identifies risk for postop problems regaining extension.

PMID- 9617727
TI  - The effects of serial stretch loading on stretch work and stretch-shorten cycle
      performance in the knee musculature.
AB  - Training methods to optimize stretch-shorten cycle performance and an active
      muscle's ability to resist a sudden stretch (stretch work) and the relationship
      between the two have not been fully explored. The purpose of this study was to
      examine the effects of an 8-week strengthening program of serial stretch loading
      on stretch work and stretch-shorten cycle performance in the quadriceps and
      hamstring muscles. Thirty-one asymptomatic subjects participated in pre- and post
      tests of maximum voluntary isometric contractions, stretch work and stretch
      shorten cycle trials, and single-leg vertical jumps. The training portion
      consisted of progressively resisted isotonic single-leg squats. One leg exercised
      against an isotonic load with serial stretch loading, while the other leg
      exercised against isotonic load alone. Training resulted in strength gains in
      both legs indicated by the increase in weight lifted during training, but not by
      maximum voluntary isometric contractions. Vertical jump height increased in both
      legs. In the hamstring, stretch work decreased and stretch-shorten cycle
      performance increased in both legs. In the quadriceps, serial stretch loading
      intervention resulted in increased stretch-shorten cycle performance and no
      significant change in stretch work. The correlation between stretch-shorten cycle
      and stretch work was weak but significant. These findings suggest that the use of
      serial stretch loading could improve muscular performance and enhance a muscle's
      potential for dynamic stabilization.

PMID- 9617728
TI  - An electromyographic study of vastus medialis oblique and vastus lateralis
      activity while ascending and descending steps.
AB  - Imbalances in the firing pattern and contraction intensity of the vastus medialis
      oblique (VMO) and the vastus lateralis (VL) have been considered important
      factors contributing to patellofemoral joint dysfunction. Vastus medialis oblique
      and vastus lateralis electromyographic (EMG) activity were measured for 15
      individuals without patellofemoral pain (asymptomatic group) and 13 subjects with
      patellofemoral pain (symptomatic group) while ascending and descending steps. The
      peak VMO/VL ratios of EMG activity and the difference in peak VMO and VL onset
      times were measured. Two-way mixed-model analyses of variance (ANOVA) were used
      to determine the main effects of group (asymptomatic and symptomatic), phase
      (concentric phase ascending and two eccentric phases descending stairs), and the
      interaction between group and phase. The ANOVAs indicated no difference between
      groups for the peak VMO/VL EMG ratio or for the onset timing between peak VMO and
      VL muscle activity. Combining groups, the peak VMO/VL EMG ratio was less for the
      eccentric weight acceptance phase of descent compared with the concentric phase
      of ascent. These findings suggest no differences between asymptomatic and
      symptomatic individuals, but differences may exist between concentric and
      eccentric VMO/VL ratios. Further research is needed to determine if VMO and VL
      muscle imbalances contribute to patellofemoral dysfunction.

PMID- 9617729
TI  - The relationship between open and closed kinetic chain strength of the lower limb
      and jumping performance.
AB  - Closed kinetic chain (CKC) exercise has become popular in rehabilitation partly
      due to the belief that it is more closely related to function than open kinetic
      chain (OKC) resistance. This study's purpose was to investigate the relationship
      between OKC and CKC strength of the lower limb extensors and functional
      performance. Twenty uninjured female subjects performed isotonic strength tests
      for the knee extensors in OKC and for the hip, knee, and ankle extensors in the
      squat exercise (CKC). Vertical and standing long jump performance was assessed
      using an optoelectric motion analysis system. Pearson product-moment correlation
      analysis showed that CKC strength scores were correlated with vertical jump
      performance (r = 0.722, p = 0.002) and standing long jump performance (r = 0.650,
      p = 0.005). Open kinetic chain strength demonstrated minimal correlation with
      vertical jump (r = 0.097) and standing long jump performance (r = 0.070). We
      conclude that lower limb extensor CKC muscle strength is more highly related to
      jumping performance than knee extensor OKC strength, but further research is
      needed to assess possible differences in training effectiveness for these two
      regimes.

PMID- 9617730
TI  - Case report: can sacroiliac joint dysfunction cause chronic Achilles tendinitis?
AB  - This case study discusses the possible relationship between chronic Achilles
      tendinitis and sacroiliac joint dysfunction. The patient presented is an active
      pole jumper, competing at both the national and international levels. He suffered
      from chronic Achilles tendinitis during the 1994-95 season, and conservative
      treatment applied locally was not successful. The athlete discarded the
      possibility of operative debridement of the tendon. Instead, an evaluation of the
      kinetic chain of the lower extremity and pelvic-lumbar area was performed, and
      the athlete was diagnosed with sacroiliac joint dysfunction and Achilles
      tendinitis. Evaluation findings, treatment program, and treatment outcome are
      also presented. The literature regarding sacroiliac joint mechanics and
      biomechanics of the foot-knee-hip and pelvic area is discussed and used to
      support the author's thesis that sacroiliac joint dysfunction, in this case a
      backward rotation of the right ilium, may have changed the kinematic chain of the
      lower extremity and caused a tendinitis in the Achilles tendon of the affected
      leg. Sacroiliac joint function and dysfunction, the reliability of sacroiliac
      joint mobility tests, and the validity of treatment programs are still considered
      controversial, and more research is needed to understand these mechanisms.

PMID- 9617731
TI  - Scapular avulsion fracture of a high school wrestler.
AB  - This case study details a rare injury managed conservatively with aggressive
      therapy with early return to competition. A 17-year-old high school wrestler
      suffered indirect trauma to the right upper extremity. The patient was forced to
      the mat where he felt pain in the posterior aspect of his shoulder and was point
      tender over the inferior pole of his right scapula. Radiographs reveal an
      avulsion fracture at the inferior angle of the scapula. Aggressive therapy
      included modalities to control inflammation and muscle guarding in addition to
      early scapular mobility. Maintenance of glenohumeral motion and upper extremity
      strengthening was started within a week. The patient was able to wrestle in the
      state tournament 3 weeks after initial injury. At the 6-month follow-up, the
      patient had no clinical tenderness, full range of motion, and no motor deficits.
      The outcome resulted in clinical and radiological healing of the fracture and no
      functional deficits.

PMID- 9617732
TI  - [Peer review in toxicologic histopathology: its necessity, type and procedure].
AB  - A histopathology peer review already has become an integral part of industrial
      toxicologic pathology in the USA and Europe. Nevertheless, the review is
      unfamiliar to toxicologic pathologists in Japan. This report provides detailed
      information on convenient, useful procedures for peer review in toxicologic
      histopathology and describes its necessity and type. Histopathology peer review
      is either informal or formal. Formal review means that the target organs to be re
      estimated and the reviewing pathologist's name are stated somewhere in a protocol
      or study report. The resolution of all diagnostic discrepancies between studies
      and reviewing pathologists must be clarified, and the review records need to be
      preserved. No audit trials need to be kept for informal peer review. Based on the
      purpose of the review, histopathology peer reviews may be classified into 3 major
      types: "complete", "problem-solving", and a "quality-monitoring" reviews. For a
      "Complete" review, all histopathologic findings crucial to the conclusion of the
      study are re-examined. A "problem-solving" review serves to re-evaluate anomalous
      findings. A "quality-monitoring" review is a periodical monitor of the quality of
      histopathologic diagnoses at pathology laboratories, particularly in toxicology
      contract research organizations. The procedures for histopathology peer review
      consist of 5 stages. At the first stage, the target organs to be reviewed are
      selected from the draft summary tables of the original findings diagnosed by the
      study pathologist, and the reviewing pathologist evaluates all selected organs.
      At the second stage, the study pathologist re-examines all the findings with
      diagnoses not accepted by the reviewing pathologist and re-considers the
      appropriateness of these original diagnoses. At the third stage, the study
      pathologist and the reviewing pathologists discuss all diagnostic differences
      until they reach a consensus opinion. At the fourth stage, the whole process
      (stage 1 to 3) of peer review of all target organs is tabulated, including the
      study pathologist's and reviewing pathologist's diagnoses, the study
      pathologist's opinions, and consensus diagnoses. At the fifth stage, Peer Review
      Certification is issued with the study pathologists' and reviewing pathologists'
      signatures. The reviewing pathologist must share the responsibility for the final
      diagnoses with the study pathologist. In order to gain greater credibility from
      regulatory agencies, a peer review performance is best made by an independent
      external pathologist.

PMID- 9617733
TI  - Effects of levofolinate calcium on subacute intravenous toxicity of 5
      fluorouracil in rats.
AB  - To clarify whether levofolinate calcium (1-LV) enhances 5-fluorouracil (5-FU)
      toxicity, a 4-week toxicity study of 5-FU (10 mg/kg/day) in combination with 1-LV
      (6, 20 or 60 mg/kg/day) was conducted in rats. In the 5-FU alone group, a
      decrease in body weight gain, food consumption, RBC parameter and WBC counts were
      detected. Histopathologically, lymphoid depletion of lymphatic organs,
      hematopoiesis enhancement of the spleen and myelosuppression were observed. In
      the group for which 5-FU was combined with 1-LV, the RBC counts decreased,
      extramedullary hematopoiesis increased and the suppression of lymphatic organs
      was enhanced. Changes in the lymphatic organs were observed at 20 mg/kg/day of 1
      LV and above. In monitoring of blood drug concentrations of 1-LV, 5-methyl
      tetrahydrofolic acid, a metabolite of 1-LV, and 5-FU after the 1st and 14th
      dosings, there was no apparent difference between 5-FU alone and 5-FU combined
      with 1-LV in Cmax and AUC0-infinity. The potentiation induced by 1-LV in the
      toxicity of 5-FU appeared to be mainly immuno-suppression and myelosuppression,
      which were related to the anti-tumor activity of 5-FU. Plasma concentrations of 5
      FU and 1-LV in this study overwhelmed the concentrations that enhancement of
      thymidylate synthetase (TS) inhibition due to 5-FU was observed by addition of 1
      LV in vitro. Therefore toxic potentiation of 5-FU due to simultaneous 1-LV dosing
      is presumed to be concerned with an increased ternary complex (FdUMP-TS-5,10
      methylenetetrahydrofolate) formation and a greater extent of TS inhibition.

PMID- 9617734
TI  - [A single dose toxicity study of magnesium sulfate in rats and dogs].
AB  - A single dose toxicity study of magnesium sulfate by intravenous administration
      was conducted in rats and dogs. The results are summarized in the following.
      Magnesium sulfate was administered once at dose levels of 90, 130, 200, 300 and
      450 mg/kg to Crj:CD(SD) rats at 6 weeks of age. Deaths occurred in the 200 mg/kg
      and above groups in both sexes. The LD50 values were 206 mg/kg for males and 174
      mg/kg for females. In the surviving animals, in the 130 mg/kg and above groups,
      tonic convulsions, abnormal gait and tachypnea were seen. However, these signs
      disappeared gradually and all animals returned to a normal state by 15 min after
      dosing. There were no treatment-related changes in the body weight or gross
      pathology. Magnesium sulfate was infused for 6 hr at dose levels of 75, 300 and
      1200 mg/kg (12.5, 50 and 200 mg/kg/hr) to female beagle dogs at 6 months of age.
      No deaths were observed in any of the dose groups and it was considered that the
      lethal dose level would be higher than 1200 mg/kg(200 mg/kg/hr). In the 1200
      mg/kg group, vomiting, decreased spontaneous movement, staggering gait, prone
      position and flush of the conjunctiva and ear auricles were seen. However, these
      signs disappeared gradually and animals returned to a normal state by 1 hr after
      dosing. There were no treatment-related changes in the body weight, food
      consumption or gross pathology.

PMID- 9617735
TI  - [A 2-week toxicity study of magnesium sulfate administered by 24-hr intravenous
      infusion in beagle dogs followed by 2-week recovery period].
AB  - A 2-week toxicity study of magnesium sulfate administered by a 24-hr intravenous
      infusion at the dosage levels of 0, 12.5, 50, 100 and 200 mg/kg/hr in female
      beagle dogs was conducted, with 2-week follow-up observation after drug
      withdrawal. One of 2 animals in the 200 mg/kg/hr group died approx. 32 hr after
      the start of infusion. At the same time, the remaining 1 animal of the same group
      was sacrificed in a moribund state. Changes attributable to the treatment of
      magnesium sulfate were decreased food consumption and body weight gain, anemia,
      mild prolongation of conduction time in electrocardiogram and tubular basophilia
      in the kidneys in the animals treated with 100 mg/kg/hr. Furthermore, decreased
      calcium level was recorded in the animals treated with 50 mg/kg/hr or more.
      However, these changes disappeared after drug withdrawal, and reversibility was
      suggested. Judging from the mode of occurrence, since the change in calcium level
      observed in the group treated with 50 mg/kg/hr was slight, it was considered to
      be toxicologically insignificant. In conclusion, the nontoxic dosage level of
      magnesium sulfate was judged to be 50 mg/kg/hr under the condition of the present
      study.

PMID- 9617736
TI  - [A 4-week toxicity study of magnesium sulfate administered by 24-hr intravenous
      infusion in beagle dogs].
AB  - A 4-week toxicity study of magnesium sulfate administered by 24-hr intravenous
      infusion at the dosage levels of 0, 12.5, 50 and 100 mg/kg/hr in female beagle
      dogs was conducted. No death occurred in any group. Changes attributable to the
      treatment with magnesium sulfate were decreased food consumption and body weight
      gain, anemic change, increased urine volume, decreased serum calcium level,
      increased inorganic phosphorus level, slight prolongation of conduction time in
      electrocardiogram and tubular basophilia in the kidneys in the group treated with
      100 mg/kg/hr. In addition, essentially similar changes were also observed at the
      same dosage level in the 2-week study of this drug, in which recoverability was
      recognized with 2-week follow-up observation after drug withdrawal. In
      conclusion, the nontoxic dosage level was judged to be 50 mg/kg/hr under the
      condition of the present study.

PMID- 9617737
TI  - [A study for effects on pre- and postnatal development, including maternal
      function in rats treated subcutaneously with magnesium sulfate].
AB  - Magnesium sulfate, at dose levels of 250, 500 and 1000 mg/kg, was administered
      subcutaneously three times daily to Crj:CD(SD) female rats from day 15 through
      day 20 of gestation. The effects of the compound on dams and F1 animals were
      examined. In the dams, decreased food consumption was observed in the 500 and
      1000 mg/kg groups. Hypolocomotion, pronation, bradypnea and decreased body weight
      gain were observed in the 1000 mg/kg group. But there were no effects on the
      delivery or lactation conditions and necropsy from administration of the test
      article. In the F1 animals, low body weight, delays in differentiation (eruption
      of lower incisor, opening of eyelid) and reversible change in ribs (wavy rib)
      were observed in the 1000 mg/kg group. But there were no effects from
      administration of the test article in viability, functional examinations,
      behavior tests or reproductive ability. Based on the above results, under the
      conditions of this study, it was concluded that the non-toxic dose levels for
      general toxicological effects on dams was 3 x 250 mg/kg/day, for reproductive
      ability of dams was 3 x 1000 mg/kg/day, and for development of F1 animals was 3 x
      500 mg/kg/day.

PMID- 9617738
TI  - [Mutagenicity studies of magnesium sulfate--reverse mutation test with bacteria
      and chromosomal aberration test with mammalian cells in culture].
AB  - The mutagenicity potential of magnesium sulfate was re-assessed using the current
      procedure of the reverse mutation test with bacteria and chromosomal aberration
      test with mammalian cells (a Chinese hamster lung fibroblast cell line; CHL/IU)
      in culture. In the reverse mutation test with bacteria, Salmonella typhimurium
      TA100, TA98, TA1535 and TA1537 and Escherichia coli WP2 uvrA were use and the
      maximum dose level was set at 5000 micrograms/plate irrespective of the absence
      or presence of metabolic activation. Five dose levels (313-5000 micrograms/plate)
      were selected for all strains except for TA98 without metabolic activation and
      for TA1537 with metabolic activation, for which 6 dose levels (156-5000
      micrograms/plate) were selected. Magnesium sulfate induced no increase in the
      number of colonies with reverse mutation in any of the strains irrespective of
      the absence of presence of metabolic activation in the dose-range-finding study
      or in the main study. In the chromosomal aberration test with mammalian cells, a
      Chinese hamster lung fibroblast cell line (CHL/IU) in culture was used and the
      maximum dose level was set at 5.0 mg/mL both in the direct and metabolic
      activation methods. Three dose levels (1.25-5.0 mg/mL) were selected. Magnesium
      sulfate induced no increase in the incidence of cells with chromosomal aberration
      or those with genome mutation (polyploidy) in any of the strains irrespective of
      the absence of presence of metabolic activation. Thus, it is concluded that
      magnesium sulfate does not have mutagenic potential under the presence
      experimental conditions.

PMID- 9617739
TI  - Acute and chronic pleural changes after the intrapleural instillation of
      mitoxantrone in rabbits.
AB  - A previous study demonstrated that the intrapleural injection of 2 mg/kg
      mitoxantrone in rabbits resulted in a degree of pleurodesis which is comparable
      to that seen after 35 mg/kg tetracycline but that the animals had a high
      mortality rate after this dose of mitoxantrone. The objective of the present
      study was to assess the acute pleural fluid findings, the acute gross and
      microscopic pleural findings, and the chronic gross and microscopic findings in
      rabbits that received mitoxantrone. Mitoxantrone, 1.5 mg/kg, was instilled
      intrapleurally in 70 lightly anesthetized male rabbits. Groups of rabbits were
      sacrificed 1, 2, 4, 7, 15, 28, and 60 days after the injection. The intrapleural
      injection of mitoxantrone resulted in an exudative effusion on day 1. The pleural
      fluid contained predominantly neutrophils and had a mean lactate dehydrogenase
      (LDH) level that exceeded 4,000 IU/liter. Over the following week the volume of
      fluid diminished, the predominant cell became the macrophage, and the LDH levels
      decreased to less than 400 IU/liter. Macroscopic examination of the pleural space
      revealed that the mean degree of pleurodesis increased progressively over the 60
      day observation period. With microscopy, the mean degree of pleural fibrosis also
      increased progressively. There were also substantial fibrosis and inflammation of
      the underlying lung and the contralateral lung. The mortality rates were low in
      the first 28 days (3/70) but subsequently increased and exceeded 80% in the
      period between 60 and 120 days. This experimental model of pleurodesis should be
      useful in future studies directed toward uncovering the mechanisms of
      pleurodesis.

PMID- 9617740
TI  - Airway eosinophilic inflammation and bronchial hyperresponsiveness after allergen
      inhalation challenge in asthma.
AB  - Allergen exposure in atopic asthmatic patients is associated with recruitment and
      activation of eosinophils in the airways. Once activated, eosinophils release
      toxic products, including the eosinophil cationic protein (ECP), able to damage
      bronchial structures and to increase bronchial hyperresponsiveness. With this
      background, the present study was designed to evaluate whether ECP levels in
      bronchoalveolar lavage (BAL) fluid could reflect, better than BAL eosinophil
      counts, the cellular activation that follows allergen exposure in atopic
      asthmatics. Twenty-two atopic patients attended the laboratory on two separate
      days. On the 1st day, they underwent methacholine (MCh) inhalation challenge to
      detect the degree of nonspecific bronchial hyperresponsiveness. On the 2nd day,
      they underwent fiberoptic bronchoscopy and BAL, at baseline or 4-6 h after
      allergen inhalation challenge. In this latter patient group, MCh challenge was
      repeated 3-5 h after allergen challenge, 1 h before fiberoptic bronchoscopy. The
      analysis of the mean baseline FEV1 values and the degree of bronchial reactivity
      to MCh (MCh Pd20) on the 1st study day did not demonstrate differences between
      the two patient groups (p > 0.1, each comparison). In addition, in the allergen
      challenged group, MCh Pd20 was decreased significantly after allergen challenge
      (151.4 micrograms/ml and 67.6 micrograms/ml, respectively, before and after
      challenge; p < 0.05). Evaluation of the different BAL cell types demonstrated
      that the proportions of eosinophils and epithelial cells were increased
      significantly in the allergen-challenged group compared with the group evaluated
      at baseline (p < 0.01 and p < 0.05, respectively). Moreover, ECP levels,
      corrected by the correspondent albumin levels (ECP/Alb), were higher in the
      allergen-challenged group compared with the group evaluated at baseline (p <
      0.05). In addition, although a positive correlation was demonstrated between BAL
      eosinophil percentages and ECP/Alb values (r = 0.72, p < 0.05) in the group
      evaluated at baseline, no links were found between these parameters in the
      allergen-challenged group (p > 0.1). However, in this latter group, a weak
      positive correlation was demonstrated between eosinophil percentages and delta
      Mch, i.e., the increased non-specific bronchial reactivity, which is observed
      after allergen challenge (r = 0.55; p < 0.05). Thus, in stable asthmatic patients
      an ongoing activation of eosinophils parallels their migration, but this
      eosinophilic inflammation is not strictly related to bronchial reactivity to Mch.
      By contrast, after allergen inhalation challenge, eosinophil recruitment and
      activation seem to follow different temporal kinetics, and eosinophilic
      inflammation may be partially associated with the degree of airway
      hyperresponsiveness.

PMID- 9617741
TI  - The gene for lysosomal protein CD63 is normal in patients with Hermansky-Pudlak
      syndrome.
AB  - Hermansky-Pudlak syndrome (HPS) is one of the few genetic disorders associated
      with severe pulmonary fibrosis. Fifty percent of affected patients die as a
      result of respiratory insufficiency. Fibrosis is thought to be caused by the
      accumulation of ceroid, an insoluble fluorescent lipoprotein, both
      extracellularly and in the lysosomes of alveolar macrophages. In addition to
      pulmonary fibrosis, HPS is characterized by oculocutaneous albinism and a
      reduction in the number of platelet dense bodies. CD63 is a protein that was
      described originally in platelet lysosomes. It localizes to the membranes of
      melanosomes and platelet dense bodies. CD63 is decreased dramatically in the
      lysosomes and dense bodies of patients with HPS. We theorized that CD63, a
      membrane protein common to lysosomes, melanosomes, and platelet dense bodies, may
      play a role in HPS. We sought to characterize the gene coding for this protein in
      HPS lymphoid cell lines. The coding region for CD63 was sequenced in control and
      HPS cell lines. Messenger RNA from HPS and normal cell lines was examined by
      Northern analysis. Genomic DNA from the same cell lines was examined by Southern
      analysis and polymerase chain reaction (PCR). CD63 protein in lymphoid cell lines
      and peripheral blood monocytes was compared by Western analysis. We found no
      mutations in the coding region of CD63 in an HPS cell line. We also found no
      diminution in the quantity of CD63 RNA by Northern analysis and no gross defects
      in the structural gene by PCR and Southern analysis, suggesting that the CD63
      structural gene, promoter, and untranslated regions were normal. Western analysis
      showed that the 43-kDa protein was present in control and HPS lymphoid cell lines
      and peripheral blood monocytes in equivalent amounts. Although CD63 is an
      attractive candidate for the primary defect of HPS, the disease is probably not
      caused by a mutation in the CD63 gene.

PMID- 9617742
TI  - BAL surfactant protein A and Clara cell 10-kDa protein levels in healthy
      subjects.
AB  - Lung surfactant protein A (SP-A) and Clara cell 10-kDa protein (CC10) are the
      most abundant proteins produced locally in the lower respiratory tract, as
      assessed in bronchoalveolar lavage (BAL) analysis. However, it is not known what
      factors influence SP-A and CC10 levels in BAL fluids, and the relationship
      between SP-A and CC10 levels in BAL fluids has been unclear. We measured SP-A and
      CC10 concentrations in BAL fluids from 11 healthy nonsmokers and 12 healthy
      smokers by enzyme-linked immunosorbent assays using specific antibodies. Mean SP
      A and CC10 levels in BAL fluids of healthy smokers were significantly lower than
      those of healthy nonsmokers. SP-A values correlated significantly with CC10 and
      phospholipid values in BAL fluids. On BAL examinations using three 50-ml
      aliquots, the mean SP-A level in the second lavage was 2.0-fold and 2.4-fold,
      respectively, of that in the first and third lavages, and the mean CC10 level in
      the first lavage was 5.0-fold and 5.6-fold, respectively, of that in the second
      and third lavages. We conclude that BAL fluid SP-A and CC10 levels are influenced
      by the BAL methods and by cigarette smoking. There is a significant positive
      correlation between SP-A and CC10 values in BAL fluids of healthy subjects.

PMID- 9617743
TI  - Short-term vs long-term dexamethasone treatment: effects on rat diaphragm
      structure and function.
AB  - The effects of dexamethasone treatment duration (2.5 vs 10 weeks) on diaphragm
      myosin heavy chain isoforms, fiber types, and contractile characteristics were
      studied in male rats. Compared with ad libitum-fed and pair-fed controls,
      dexamethasone significantly decreased body weight, costal diaphragm weight, and
      the relative expression of myosin heavy chain isoform MHC-2B. Compared with pair
      fed controls, the effect on MHC-2B expression was greater after 10 weeks than
      after 2.5 weeks. Type I and type II costal diaphragm fiber atrophy occurred, and
      type II fiber atrophy was greater after 10 weeks. Costal diaphragm-specific
      forces were not affected significantly by dexamethasone, regardless of the
      treatment duration or control group comparison. Fatigue resistance indexes were
      increased significantly after long term treatment compared with pair-fed controls
      and after both short-term and long-term treatment compared with ad libitum-fed
      controls. In conclusion, the effects of dexamethasone on MHC isoform phenotype
      expression, fiber type costal diaphragm atrophy, and fatigue resistance were
      dependent on treatment duration, with greater effects after long-term (10 weeks)
      treatment.

PMID- 9617744
TI  - Cough receptor sensitivity to capsaicin and tartaric acid in patients with
      Mycoplasma pneumonia.
AB  - There has been no detailed study of cough sensitivity during acute lower
      respiratory infection. The aim of this study was to clarify cough sensitivity in
      Mycoplasma pneumonia, which is a well known acute lower respiratory infection
      with persistent nonproductive cough. We examined cough sensitivity to inhaled
      capsaicin and tartaric acid in both the acute and the convalescent phases of
      Mycoplasma pneumonia, cell differentials in bronchoalveolar lavage fluid, and
      pathologic findings of transbronchoscopic bronchial biopsy specimens. Although
      dry cough was observed in all patients during Mycoplasma pneumonia, cough
      sensitivity in the acute phase [capsaicin: 19.8 (GSEM, 0.214) microM, tartaric
      acid: 0.26 (GSEM, 0.356) M] were not enhanced compared with those in both control
      subjects [capsaicin: 27.9 (GSEM, 1.24) microM, tartaric acid: 0.316 (GSEM, 0.079)
      M] and patients in the convalescent phase [capsaicin: 15.7 (GSEM, 0.219) microM,
      tartaric acid: 0.50 (GSEM, 0.326) M] when all symptoms including cough had
      disappeared. The percentage of lymphocytes and neutrophils in bronchoalveolar
      lavage fluid BALF was significantly greater than in the control subjects, and
      lymphocyte-dominant bronchitis was observed in biopsied specimens. We conclude
      that cough threshold to inhaled capsaicin or tartaric acid was not enhanced
      during acute Mycoplasma pneumonia with lymphocyte-predominant bronchitis. This is
      the first report examining cough sensitivity in patients with acute lower
      respiratory infection with pneumonia.

PMID- 9617745
TI  - Long term cigarette smoke exposure does not increase airway responsiveness in
      rats.
AB  - To ascertain whether chronic cigarette smoke exposure induces increased airway
      responsiveness, we performed methacholine response tests in Sprague-Dawley rats
      by calculating pulmonary resistance after nebulization of saline followed by an
      increasing concentration of methacholine. We also calculated the concentration of
      methacholine which doubled the baseline resistance (R200). Tests were performed
      at baseline and after 2, 4, 8, and 12 months of exposure to the smoke of seven
      cigarettes per day, 5 days each week; control animals were exposed to room air.
      At the completion of the study, there were 13 rats in the smoke-exposed group and
      7 rats remaining in the control group. Airway morphology was assessed using a
      point counting technique. We found that (1) chronic exposure to cigarette smoke
      did not alter either the baseline resistance or the R200; (2) the saline baseline
      resistance decreased over time in the control animals; and (3) at the 12-month
      time point, smokers with increased baseline airway resistance had greater amounts
      of airway smooth muscle compared with the smoke-exposed animals without increased
      resistance. We conclude that in this animal model, long term exposure to
      cigarette smoke did not alter the response to methacholine but did increase
      airway smooth muscle and baseline resistance in some but not all animals.

PMID- 9617746
TI  - Is there a rationale for the use of acetylcholinesterase inhibitors in the
      therapy of Alzheimer's disease?
AB  - Since the 1980s, the cholinergic hypothesis of the pathogenesis of Alzheimer's
      disease has proven to be a strong stimulus to pharmacological strategies aimed at
      correcting the cognitive deficit by manipulating cholinergic neurotransmission.
      Among these strategies, the one based on acetylcholinesterase inhibition is
      currently the most extensively developed for the therapy of Alzheimer's disease.
      The inhibitors' mechanisms of action are complex, including changes in the
      release of acetylcholine, and modulation of acetylcholine receptors. Various
      clinical trials of various inhibitors have shown that, on the whole, their
      effects were modest and, in the case of some drugs, were associated with frequent
      adverse reactions. Among the conceivable reasons for the limited efficacy of
      these drugs, those related to the pharmacological target deserve particular
      attention. This review, therefore, focuses on the complex nature of the
      acetylcholine system, the alterations of acetylcholinesterase and muscarinic
      receptor signal transduction in Alzheimer's disease, and the involvement of other
      neurotransmitters.

PMID- 9617747
TI  - The functional sensitisation of sigma receptors following chronic selective
      serotonin reuptake inhibitor treatment.
AB  - The purpose of the present study was to investigate the potential impairment of
      normal motor function following chronic selective serotonin reuptake inhibitor
      treatment that may result from sensitisation of sigma receptors. Rats were
      chronically treated with either sertraline, citalopram, paroxetine or fluvoxamine
      and a selective sigma receptor ligand, di-o-tolylguanidine (DTG), for 28 days.
      All animals then received an acute intra-rubral injection of either DTG or
      saline. Following the direct injection of DTG into the red nucleus, rats
      chronically treated with DTG exhibit a maximal behavioural response characterised
      as a pronounced dystonia. Animals chronically treated with sertraline and
      citalopram elicited a response similar to that of control animals following the
      acute DTG challenge, whereas chronic treatment with paroxetine and fluvoxamine
      significantly decreased and increased the dystonic response, respectively. Facial
      spasticity and vacuous chewing movements were associated with, and reflected the
      extent of, the DTG-induced dystonia. Changes in regional biogenic amine
      concentrations were also determined. The concentrations of serotonin and
      noradrenaline were determined in the brain stem and cerebellum following the
      intra-rubral injection of either saline or DTG in animals that had been
      chronically treated with a selective serotonin reuptake inhibitor or DTG. There
      was a significant increase in serotonin concentration in the brain stem as a
      result of chronic DTG and fluvoxamine treatments. The increase in serotonin
      correlated with the reported potentiation of dystonia in animals that received 28
      days treatment with these drugs. The potentiation of dystonia following chronic
      DTG and fluvoxamine treatments suggests that these drugs sensitise the sigma2
      receptors, an effect that does not appear to be shared by citalopram, sertraline
      or paroxetine.

PMID- 9617748
TI  - Antinociceptive effects of the novel neuronal nicotinic acetylcholine receptor
      agonist, ABT-594, in mice.
AB  - ABT-594 [5-((2R)-azetidinylmethoxy)-2-chloropyridine], a novel neuronal nicotinic
      acetylcholine receptor agonist, produced significant antinociceptive effects in
      mice against both acute noxious thermal stimulation--the hot-plate and cold-plate
      tests--and persistent visceral irritation--the abdominal constriction (writhing)
      assay (maximally-effective dose in each test 0.62 micromol/kg, i.p.). This effect
      was not stereoselective since the S-enantiomer, A-98593 [5-((2S)
      azetidinylmethoxy)-2-chloropyridine], produced similar antinociceptive effects in
      this dose range. The effect in the hot-plate test peaked at 30 min after i.p.
      administration and was still present 60 min, but not 120 min, after injection.
      ABT-594 was orally active, but 10-fold less potent by this route than after i.p.
      administration. The antinociceptive effect of ABT-594 was prevented, but not
      reversed, by the noncompetitive neuronal nicotinic acetylcholine receptor
      antagonist mecamylamine (5 micromol/kg, i.p.). In contrast, the antinociceptive
      effect of ABT-594 was not prevented by hexamethonium (10 micromol/kg, i.p.), a
      neuronal nicotinic acetylcholine receptor antagonist that does not readily enter
      the central nervous system, nor by naltrexone (0.8 micromol/kg), an opioid
      receptor antagonist. Thus, initiation of antinociception by ABT-594 involves
      activation of central nicotinic acetylcholine receptors, but does not require
      activation of naltrexone-sensitive opioid receptors. The antinociceptive effects
      of morphine and ABT-594 in the mouse hot-plate test appeared to be additive, but
      ABT-594 did not potentiate the respiratory depression produced by morphine when
      the two compounds were coadministered. ABT-594 reduced body temperature and
      spontaneous exploration in the antinociceptive dose range, but did not reliably
      impair motor coordination in the rotarod test. Thus, it is unlikely that the
      antinociceptive effects result simply from impaired motor function. The compound
      also produced an anxiolytic-like effect in the elevated plus maze (at 0.019 and
      0.062 micromol/kg, i.p.). Preliminary safety testing revealed an ED50 for overt
      seizure production of 1.9 micromol/kg, i.p. and an LD50 of 19.1 micromol/kg i.p.
      in mice, values 10 and 100 times the minimum effective antinociceptive dose of
      the compound. ABT-594 increased the duration of ethanol-induced hypnotic effects,
      tended to increase pentobarbital-induced hypnotic effects (P = 0.0502), and had
      no effect on pentobarbital-induced lethality. These data indicate that ABT-594 is
      a centrally acting neuronal nicotinic acetylcholine receptor agonist with potent
      antinociceptive and anxiolytic-like effects in mice.

PMID- 9617749
TI  - Cardiovascular effects of centrally injected tetrahydroaminoacridine in conscious
      normotensive rats.
AB  - In freely moving rats, intracerebroventricularly (i.c.v.) injected
      tetrahydroaminoacridine (10, 25, 50 microg) increased blood pressure and
      decreased heart rate in a dose- and time-dependent manner. Intravenous (i.v.)
      tetrahydroaminoacridine (1 and 3 mg/kg) also increased blood pressure. Atropine
      sulphate (10 microg; i.c.v.) pretreatment greatly attenuated the blood pressure
      response to i.c.v. tetrahydroaminoacridine while mecamylamine (50 microg; i.c.v.)
      failed to change the pressor effect. Neither atropine sulphate nor mecamylamine
      pretreatment affected the bradycardia induced by tetrahydroaminoacridine.
      However, the bradycardic response was completely blocked by atropine
      methylnitrate (2 mg/kg; i.p.) pretreatment. The pressor response to i.c.v.
      tetrahydroaminoacridine was associated with a several-fold increase in plasma
      levels of vasopressin, adrenaline and noradrenaline, but not of plasma renin.
      Pretreatment with prazosin (0.5 mg/kg; i.v.) attenuated the pressor effect
      without changing the bradycardia. Vasopressin V1 receptor antagonist [beta
      mercapto-beta,beta-cyclopentamethylenepropionyl1,O-Me-Tyr2-A rg8]vasopressin (10
      microg/kg; i.v.) pretreatment also partially inhibited the pressor response to
      i.c.v. tetrahydroaminoacridine and abolished the bradycardia.
      Tetrahydroaminoacridine's cardiovascular effects were completely blocked when
      rats were pretreated with prazosin plus vasopressin antagonist. The data show
      that tetrahydroaminoacridine increases blood pressure in normotensive freely
      moving rats by activating central muscarinic cholinergic transmission. Increases
      in plasma catecholamines and vasopressin are both involved in this response. The
      tetrahydroaminoacridine-induced reduction in heart rate appears to be due to the
      increase in vagal tone and plasma vasopressin.

PMID- 9617751
TI  - Anandamide and endothelium-derived hyperpolarizing factor act via a common
      vasorelaxant mechanism in rat mesentery.
AB  - We have recently proposed that an endocannabinoid, of which anandamide is
      prototypic, may be an endothelium-derived hyperpolarizing factor (EDHF). In the
      present study, both anandamide-induced and EDHF-mediated relaxations were
      insensitive to either charybdotoxin (100 nM) or apamin (500 nM) alone, but were
      inhibited by these agents in combination. These results point to EDHF and
      anandamide acting at a common site to cause vasorelaxation via K+ channel
      activation, and support our proposal that an endocannabinoid is an EDHF.

PMID- 9617750
TI  - Role of endothelin ET(A) receptors in the hypertension produced by 4-day L
      nitroarginine methyl ester and cyclosporine treatment.
AB  - Studies were designed to examine the influence of endothelin type A receptor
      (ETA) blockade on the hypertensive and renal response to 4 day treatment with the
      nitric oxide (NO) synthase inhibitor, L-nitroarginine methyl ester (L-NAME), and
      cyclosporine. In the first series of experiments, male Sprague-Dawley rats
      maintained in metabolic cages were given the L-NAME at 50 mg/100 ml in the
      drinking water with or without the ETA receptor antagonist, A-127722 (2-(4
      methoxyphenyl)-4-(1,3-benzodioxol-5-yl)-1-[[(dibutyl amino)carbonyl]methyl]
      pyrrolidine-3-carboxylic acid; 10 mg kg(-1) day(-1)), in either food or water.
      After 4 days, tail cuff estimates of systolic arterial pressure and a blood
      sample were obtained. A-127722 prevented the rise in tail cuff pressure produced
      by L-NAME. In the second series of experiments, rats were given cyclosporine at
      20 mg kg(-1) day(-1) (i.p.) or cyclosporine plus L-NAME. Control groups were
      given olive oil (1 ml/kg i.p.). Treatment with cyclosporine alone had no effect
      on tail cuff pressure or plasma creatinine, but significantly attenuated the
      normal increase in body weight over the 4-day period. The combination of
      cyclosporine plus L-NAME significantly increased both tail cuff pressure and
      plasma creatinine and completely prevented any gain in body weight. L-NAME plus
      olive oil produced a significant increase in tail cuff pressure but changed no
      other variable. To determine the role of ETA receptors in this setting, a final
      series of rats were treated with cyclosporine and L-NAME along with A-127722 in
      the drinking water. ETA receptor blockade had no effect on the increase in tail
      cuff pressure, plasma creatinine or the attenuated weight gain. These results
      indicate that subchronic (4-day) L-NAME hypertension is maintained, at least in
      part, by activation of ETA receptors although the hypertensive and renal response
      to combined L-NAME and cyclosporine treatment does not involve ETA receptor
      activation. These results support the hypothesis that endothelial dysfunction
      predisposes the kidney to functional derangements associated with cyclosporine.

PMID- 9617752
TI  - Compared effects of natriuretic peptides on ovalbumin-induced asthmatic model.
AB  - We compared the effects of natriuretic peptides on antigen-induced
      bronchoconstriction and airway microvascular leakage in sensitized guinea pigs.
      Anesthetized male guinea pigs, ventilated via a tracheal cannula, were placed in
      a plethysmograph to measure pulmonary mechanics for 10 min after challenge with 1
      mg/kg of ovalbumin, and then Evans blue dye was extravasated into airway tissue
      in order to indicate and evaluate microvascular leakage. Three separate
      intravenous pretreatments using atrial natriuretic peptide (ANP), brain
      natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) significantly
      inhibited the ovalbumin-induced bronchoconstriction and microvascular leakage in
      a dose-dependent manner. These inhibitory effects were mimicked by 8
      bromoguanosine 3',5'-cyclic monophosphate. We showed that the rank order of
      inhibitory potencies, which were mediated by cyclic guanosine 3',5'
      monophosphate, was BNP > or = ANP > or = CNP. These results gave us some clues
      for the clinical application of the natriuretic peptides.

PMID- 9617753
TI  - Effects of nimodipine and isradipine on endothelin-1-induced contraction of
      pregnant rat myometrium.
AB  - The purpose of this study was to investigate the effect of nimodipine and
      isradipine on endothelin-1-induced contractions of isolated pregnant rat
      myometrium. Endothelin-1 at 10(-10)-10(-8) M dose-dependently increased the
      amplitude and frequency of contractions and decreased the duration of
      contractions. Basal tone of myometrium was increased with the higher endothelin-1
      concentrations (10(-9) and 10(-8) M). After pretreatment for 30 min with 10(-6) M
      nimodipine or 10(-5) M isradipine, amplitude and duration of endothelin-1-induced
      contractions were significantly decreased, but frequency of myometrial
      contractions increased markedly. However, neither agent abolished the stimulating
      effect of higher endothelin-1 concentrations (10(-9) and 10(-8) M) on the basal
      tone. Our study showed that phasic activity is inhibited by nimodipine and
      isradipine, whereas tonic activity is not inhibited. The contraction of
      myometrial strips isolated from the pregnant rat may be modulated by endothelin
      1, and this effect is only partly modulated by dihydropyridine-type Ca2+
      channels. The remaining resistance to nimodipine- and isradipine-induced
      inhibition may be explained by pregnancy-associated changes in the other
      electrophysiological and biochemical factors.

PMID- 9617754
TI  - Effects of atipamezole, detomidine and medetomidine on release of steroid
      hormones by porcine adrenocortical cells in vitro.
AB  - The 4-substituted imidazole type alpha2-adrenoceptor ligands atipamezole,
      detomidine, and medetomidine were screened for actions on the release of
      aldosterone by a suspension of porcine adrenocortical cells with
      deoxycorticosterone (1 microM) as substrate. Progesterone, pregnenolone or
      corticosterone (all at 1 microM) were also used as substrates. With pregnenolone
      as substrate, drug-induced effects on the output of nine steroids (aldosterone,
      corticosterone, cortisol, deoxycortisol, testosterone, progesterone, 17alpha
      hydroxyprogesterone, androstenedione, dehydroepiandrosterone) were monitored
      simultaneously. The alpha2-adrenoceptor antagonist atipamezole was a potent
      inhibitor of aldosterone release (range 10-1000 nM). The sedative alpha2
      adrenoceptor agonists medetomidine and detomidine also inhibited aldosterone
      release (range 10-1000 nM). With pregnenolone as substrate, the inhibition
      induced by 4-substituted imidazoles of the release of corticosterone and cortisol
      was more pronounced than that of aldosterone. Androstenedione and deoxycortisol
      release was enhanced. The 4-substituted imidazoles atipamezole, detomidine, and
      medetomidine inhibited mitochondrial cytochrome P450(11beta/18) in vitro. This
      inhibition was unrelated to their alpha2-adrenoceptor actions. The 4-substituted
      imidazole type alpha2-adrenoceptor ligands used to control sedation/anaesthesia
      can alter the steroid-based defence mechanisms of the body.

PMID- 9617755
TI  - Masoprocol (nordihydroguaiaretic acid): a new antihyperglycemic agent isolated
      from the creosote bush (Larrea tridentata).
AB  - An ethnomedically-driven approach was used to evaluate the ability of a pure
      compound isolated from the creosote bush (Larrea tridentata) to lower plasma
      glucose concentration in two mouse models of type 2 diabetes. The results
      indicated that plasma glucose concentration fell approximately 8 mmol/l in male
      C57BL/ks-db/db or C57BL/6J-ob/ob mice following the oral administration of
      masoprocol (nordihydroguaiaretic acid), a well known lipoxygenase inhibitor. The
      decline in plasma glucose concentration following masoprocol treatment in the
      mice was achieved without any change in plasma insulin concentration. In
      addition, oral glucose tolerance improved and the ability of insulin to lower
      plasma glucose concentrations was accentuated in masoprocol-treated db/db mice.
      These data raise the possibility that masoprocol, or other lipoxygenase
      inhibitors, represents a new approach to the pharmacological treatment of Type 2
      diabetes.

PMID- 9617756
TI  - Effects of SA6541, a leukotriene A4 hydrolase inhibitor, and indomethacin on
      carrageenan-induced murine dermatitis.
AB  - We investigated the effects of S-(4-dimethylaminobenzyl)-N-[(2S)-3-mercapto-2
      methylpropionyl]-L- cysteine (SA6541), a potent leukotriene A4 hydrolase
      inhibitor. on early phase of carrageenan-induced dermatitis model. Carrageenan
      injection induced edema and neutrophil influx in the mouse ear. SA6541 inhibited
      edema formation and neutrophil influx. SA6541 also inhibited leukotriene B4
      production but not prostaglandin E2 production in the mouse ear. On the other
      hand, indomethacin inhibited edema formation but not neutrophil influx.
      Indomethacin also inhibited prostaglandin E2 production but not leukotriene B4
      production. Combination therapy with SA6541 and indomethacin strongly inhibited
      edema formation in comparison with treatment with either agent alone. These
      results suggest that leukotriene B4 may be important in the pathogenesis of
      dermatitis.

PMID- 9617757
TI  - Human neuropeptide YY1 receptors exert unequal control of the extracellular
      acidification rate in different cell lines.
AB  - The ability of the human neuropeptide YY1 receptor subtype to increase the
      extracellular acidification rate in different cell lines was investigated by
      using the Cytosensor Microphysiometer. In CHO-Y1 cells (Chinese Hamster Ovary
      cells expressing the cloned human neuropeptide YY1 receptor), neuropeptide Y
      increased the acidification rate by up to 15% of the basal level with a 
      Log(EC50) of 7.42. As expected for neuropeptide YY1 receptors, this response was
      potently inhibited by the neuropeptide YY1-selective non-peptide antagonist
      BIBP3226 ((R)-N2-(diphenylacetyl)-N-[(4-hydroxy-phenyl)methyl]-D-arginine amide).
      Its enantiomer BIBP3435 ((S)-N2-(diphenylacetyl)-N-[(4-hydroxy-phenyl)methyl]-D
      arginin amide) was less potent. The antagonists themselves did not affect the
      extracellular acidification rate at concentrations up to 10 microM. In SK-N-MC
      cells (a neuroblastoma cell line of human origin that expresses the neuropeptide
      YY1 receptor) no change of the acidification rate could be observed in the
      presence of neuropeptide Y at concentrations up to 1 microM. For control, the
      neuropeptide YY1 receptors were also investigated by assessing whole cell
      radioligand binding and, at the functional level, by assessing their ability to
      decrease the forskolin-induced accumulation of cAMP. The specific (i.e.,
      neuropeptide Y-displaceable) binding of [3H]neuropeptide Y was to a homogeneous
      class of high-affinity sites in both SK-N-MC and CHO-Y1 cells. The equilibrium
      dissociation constants for [3H]neuropeptide Y, the total number of binding sites
      and the kinetic constants for association and for dissociation were similar.
      Neuropeptide Y produced a dose-dependent inhibition of forskolin-induced cAMP
      accumulation in SK-N-MC cells (-log(EC50) = 9.40) but it did not affect cAMP
      accumulation in CHO-Y1 cells. Non-transfected CHO-K1 cells were used as negative
      control throughout the study. No binding or response could be observed in these
      cells. Our data suggest that the signalling mechanisms of neuropeptide YY1
      receptors are closely related to the cell type in which they are expressed.

PMID- 9617758
TI  - Radical releasing properties of nitric oxide donors GEA 3162, SIN-1 and S-nitroso
      N-acetylpenicillamine.
AB  - The nitric oxide (NO)-, superoxide anion (O2.-)- and peroxynitrite (ONOO-)
      releasing properties of 1,2,3,4-oxatriazolium,5-amino-3-(3,4-dichlorophenyl)
      chloride (GEA 3162) were characterized and compared with the known NO-donors 3
      morpholino-sydnonimine (SIN-1) and S-nitroso-N-acetylpenicillamine. All the three
      compounds released NO in aqueous solutions in a dose-dependent manner as measured
      by ozone-chemiluminescence. GEA 3162 produced more NO than SIN-1, but less than S
      nitroso-N-acetylpenicillamine during a 45 min incubation time. SIN-1 reduced
      nitro blue tetrazolium and the effect was inhibitable by superoxide dismutase.
      Reduction of nitro blue tetrazolium was not detected in the solutions of GEA 3162
      and S-nitroso-N-acetylpenicillamine suggesting that SIN-1 but not GEA 3162 and S
      nitroso-N-acetylpenicillamine release O2.- in their decomposition process.
      Formation of ONOO- in solutions of GEA 3162, SIN-1 and S-nitroso-N
      acetylpenicillamine was estimated indirectly by measuring the formation of
      nitrotyrosine. The data indicate that ONOO- was produced in the presence of SIN-1
      but not in solutions of GEA 3162 and S-nitroso-N-acetylpenicillamine. The results
      suggest that GEA 3162 produces negligible amounts of O2.- and ONOO- as compared
      to SIN-1. This adds the value of GEA 3162 as an useful tool in NO research and
      could well explain the earlier findings on the superior NO-like biological
      activity of oxatriazole derivatives as compared to SIN-1.

PMID- 9617759
TI  - Characterization of the antiplatelet effects of (2S)-5-methoxy-6-methylflavan-7
      ol from Draconis Resina.
AB  - (2S)-5-methoxy-6-methylflavan-7-ol (MMF) was purified from Draconis Resina and
      its in vitro effects on various aspects of platelet reactivity were examined.
      Results indicated that MMF dose dependently inhibited aggregation of washed
      rabbit platelets induced by collagen, arachidonic acid, ADP, U46619 or platelet
      activating factor (PAF), with IC50) values of 17.2, 49.8, 179.8, 109.6, and 189.2
      microM, respectively. Concomitantly, MMF also dose dependently suppressed ATP
      release by platelets activated by these stimulants. The increase in intracellular
      free calcium ([Ca2+]i), elicited by these activating agents, was inhibited by MMF
      as reflected by fura-2 fluorescence measurements. However, MMF had no effects on
      the cyclic AMP level of platelets. In addition, MMF inhibited the arachidonic
      acid-induced thromboxane B2 and prostaglandin D2 formation in intact platelet
      suspensions or homogenized platelet lysates. This study provided evidence that
      MMF is an antiplatelet agent whose activity is likely related to cyclooxygenase
      inhibition and suppression of [Ca2+]i increase.

PMID- 9617760
TI  - Endomorphin-1 and endomorphin-2 are partial agonists at the human mu-opioid
      receptor.
AB  - Recently two tetrapeptide ligands that bind preferentially to the mu-opioid
      receptor were identified and named endomorphin-1 and endomorphin-2. We examined
      the ability of these peptides to stimulate G protein activation in human mu
      opioid receptor transfected B82 fibroblasts as measured by [35S]GTPgammaS binding
      to cell membranes. Both endomorphin-1 and -2 act as partial agonists in this
      assay system compared with the mu-selective agonist [D-Ala2,N-Me-Phe4, Gly
      ol5]enkephalin (DAMGO). In addition, endomorphins demonstrate efficacy similar to
      morphine. These findings demonstrate that endomorphin peptides have similar
      activity at the mu-opioid receptor as morphine and suggest that these peptides
      have the potential to modulate neuronal activity in vivo.

PMID- 9617761
TI  - 11,12-Epoxyeicosatrienoic acid stimulates tyrosine kinase activity in porcine
      aortic endothelial cells.
AB  - Although epoxyeicosatrienoic acids, cytochrome P-450 mono-oxygenase metabolites
      of arachidonic acid, have been demonstrated to play a crucial role in endothelial
      cell Ca2+ homeostasis and endothelium-dependent vasorelaxation, the understanding
      of the actions of epoxyeicosatrienoic acids is limited. In this study, the effect
      of epoxyeicosatrienoic acids on tyrosine kinase in endothelial cell homogenate
      was investigated. 11,12-Epoxyeicosatrienoic acid increased tyrosine kinase
      activity in a concentration dependent manner (EC50 = 11.7 nM). Arachidonic acid
      in much higher concentrations (20 microM) mimicked the effect of the
      epoxyeicosatrienoic acid on tyrosine kinase. This effect of arachidonic acid was
      abolished in the presence of the cytochrome P-450 mono-oxygenase inhibitor
      thiopentone sodium, indicating that arachidonic acids needs to be converted to
      epoxyeicosatrienoic acids by the endothelial cytochrome P-450 mono-oxygenase to
      stimulate tyrosine kinase. These data describe a novel aspect of the actions of
      epoxyeicosatrienoic acids, and show that in addition to K+ channel activation,
      epoxyeicosatrienoic acids also regulate tyrosine kinase activated signaling
      pathways in endothelial cell activation.

PMID- 9617762
TI  - Modulation of actomyosin ATPase by goniodomin A differs in types of cardiac
      myosin.
AB  - Goniodomin A causes the conformational change of actin to modify actomyosin
      ATPase activity [Furukawa, K.-I., Sakai, K., Watanabe, S., Maruyama, K.,
      Murakami, M., Yamaguchi, K., Ohizumi, Y., 1993. Goniodomin A induces modulation
      of actomyosin ATPase activity mediated through conformational change of actin. J.
      Biol. Chem. 268, 26026-26031]. Goniodomin A inhibited the ATPase activities of
      atrial myofibrils, myosin B and reconstituted actomyosin in a concentration
      dependent manner. Interestingly, these ATPase activities of ventricular muscle
      were enhanced by goniodomin A (3 x 10(-8)-3 x 10(-7) M), but were decreased when
      the concentration was further raised. The stimulatory effect of goniodomin A was
      significantly inhibited by troponin tropomyosin complex. These results suggest
      that goniodomin A affects actin to modify cardiac actomyosin ATPase activity, and
      that this modulation differs in types of cardiac myosin.

PMID- 9617763
TI  - Down-regulation of phospholipase C-beta1 following chronic muscarinic receptor
      activation.
AB  - To determine whether prolonged activation of a phospholipase C-coupled receptor
      can lead to a down-regulation of its effector enzyme, SH-SY5Y neuroblastoma cells
      were incubated for 24 h with the muscarinic receptor agonist, oxotremorine-M.
      Under these conditions, significant reductions (46-53%) in muscarinic cholinergic
      receptor density, G(alphaq/11) and phospholipase C-beta1 (but not the beta3-or
      gamma1 isoforms) were observed. These results suggest that a selective down
      regulation of phospholipase C-beta1 may play a role in adaptation to chronic
      muscarinic receptor activation.

PMID- 9617764
TI  - The putative 116 kDa osteoclast specific vacuolar proton pump subunit has
      ubiquitous tissue distribution.
AB  - The pharmacological profile of the osteoclast proton pump has been demonstrated
      to be unique and to be the most active of all acid transport systems thus far
      studied. The recently reported putative 116 kDa osteoclast specific vacuolar
      proton pump subunit could possibly explain the unique nature of this proton pump.
      Here, we demonstrate however, that the osteoclast 116 kDa subunit is not
      osteoclast specific but has ubiquitous expression in human tissue.

PMID- 9617765
TI  - Characterization of the coat protein gene of mite-transmitted blackcurrant
      reversion associated nepovirus.
AB  - The nucleotide sequence of the 3' terminal 3105 nucleotides (nt) of RNA2 of
      blackcurrant reversion associated virus (BRAV), the first mite-transmitted member
      of the nepovirus group, has been determined. The sequence contains an open
      reading frame of 1744 nt in the virus-sense strand, a 3' untranslated region of
      1360 nt and a 3' poly(A) tail. Analysis of the amino-terminal residues of
      purified coat protein (CP) suggests that the CP gene is located between nts 1361
      and 2959 (from the 3' terminus) in the RNA2, and that Asp/Ser is the proteolytic
      cleavage site of CP in the RNA2 encoded polyprotein. The predicted translation
      product from the CP gene is a polypeptide of 533 amino acids with a calculated Mr
      of 57 561. The amino acid sequence of BRAV CP showed highest similarity to
      blueberry leaf mottle virus (BLMV), and tomato ringspot virus (ToRSV), two
      members of the proposed sub-group three of nepoviruses possessing large RNA2
      components. Nucleic and amino acid sequence comparisons between BRAV CP and the
      CPs of other nepoviruses indicate that specific conserved nepovirus CP domains
      occur in the BRAV CP thus confirming that BRAV is a member of the subgroup three
      of nepoviruses. reserved.

PMID- 9617766
TI  - Interactions between cellular actin and human respiratory syncytial virus (HRSV).
AB  - Actin the main component of the cellular microfilament network, is present in
      human respiratory syncytial virus (HRSV) purified virions, as an internal
      component. This fact and the results of immunoprecipitation studies indicate that
      during HRSV infection in HEp-2 cells there are interactions between cellular
      actin and viral components, that can promote a transitory increase in the
      polymerization of synthetized actin, mainly of the beta isotype. This increased
      actin polymerization can be related with the formation of cytoplasmic extensions,
      that contain beta actin and viral particles observed in the HRSV infected HEp-2
      cells. The formation of these structures may indicate that HRSV has developed an
      actin-based motility system similar to that described for other viral and
      bacterial systems.

PMID- 9617767
TI  - Mutational analysis of discontinuous epitopes of foot-and-mouth disease virus
      using an unprocessed capsid protomer precursor.
AB  - An unprocessed capsid precursor (P1) of foot-and-mouth disease virus (FMDV) has
      been expressed in mammalian cells to study discontinuous epitopes involved in
      viral neutralization. Amino acid replacements found in virus-escape mutants were
      engineered in the P1 precursor by site-directed mutagenesis of the plasmid. In
      all cases the replacements abolished recognition of unprocessed P1 by the
      relevant monoclonal antibodies (MAbs), paralleling the effects of the
      corresponding substitutions in neutralization of infectious FMDV. Five capsid
      surface residues within the same discontinuous antigenic area that were never
      found replaced in escape mutants were also engineered in P1. None of the
      substitutions affected antibody recognition, suggesting that these residues were
      not directly involved in the interaction with the antibodies tested. The results
      validate site-directed mutagenesis of constructs encoding capsid precursors as an
      approach to probe the structure of viral discontinuous epitopes not amenable to
      analysis with synthetic peptides.

PMID- 9617768
TI  - The expression of the essential nuclear splicing factor SC35 is altered by human
      immunodeficiency virus infection.
AB  - In order to identify cellular genes differentially expressed during human
      immunodeficiency virus 1 (HIV-1) infection, we conducted a screen using
      differential display. The sequence of one of the clones, 0085, was identical to a
      sequence present in the RNA splicing factor SC35. Since splicing is an essential
      point of control during HIV gene expression, we carried out additional
      experiments to examine SC35 expression during HIV infection. RNA blots confirmed
      that SC35 RNA was induced following HIV infection; a 2-3-fold increase in
      expression of SC35 RNA was detected by day 2 of HIV infection. Fluorescence
      activated cell-sorting revealed concomitant increases in SC35 protein and double
      staining studies demonstrated that increases in SC35 protein occurred
      specifically in the HIV-infected cells. Laser scanning confocal microscopy
      revealed SC35 was associated with 2 microm 'nuclear speckles' in both infected
      and uninfected cells, suggesting that increases in SC35 accumulated in these
      nuclear structures and that HIV infection did not alter the intracellular
      distribution of SC35. These findings indicate that an essential splicing factor
      is induced after HIV infection, suggesting that the consequences of HIV infection
      include alterations in relative levels of a splicing factor.

PMID- 9617769
TI  - The complete sequence of four major structural proteins of African horse sickness
      virus serotype 6: evolutionary relationships within and between the orbiviruses.
AB  - The amino acid sequences of four major capsid proteins of African horse sickness
      virus (serotype 6, AHSV-6) have been determined from analyses of cDNA clones
      representing the L2, L3, M6 and S7 RNA segments. The AHSV-6 L3 RNA segment has an
      open reading frame of 2715 base pairs and encodes the inner capsid protein VP3
      which comprises 905 amino acids. The VP3 layer forms the subcore of the virion
      and is surrounded by the VP7 protein which is encoded by the S7 gene. The AHSV-6
      S7 gene was found to be 1047 nucleotides in length with a coding capacity for the
      VP7 protein of 349 amino acids. These core proteins are encapsulated by the outer
      capsid proteins VP5 and VP2 which are encoded by the M6 and L2 genes
      respectively. The M6 gene of AHSV-6 was determined to be 1564 nucleotides in
      length and encoded a protein product of 504 amino acids while the L2 gene
      comprised 3203 nucleotides which encoded a predicted protein product of 1051
      amino acids. Comparison of these four sequences with the core protein sequences
      of other serotypes of African horse sickness virus, Bluetongue virus which
      infects sheep, and Epizootic haemorrhagic disease virus of deer, demonstrated
      that despite the pathobiological properties and host range of these distinct
      orbiviruses, extreme conservation is evident within the capsid genes. Sequence
      analyses also suggested that the similarity levels between serogroups depict the
      structure and function of the individual capsid proteins. The data indicated that
      the evolution of the capsid genes of gnat transmitted orbiviruses is strongly
      influenced by functional and structural constraints.

PMID- 9617770
TI  - The recombinant nucleocapsid protein of classical swine fever virus can act as a
      transcriptional regulator.
AB  - The cDNA of the nucleocapsid (core) protein of classical swine fever virus (CSFV)
      was generated by reverse transcription-polymerase chain reaction (RT-PCR) and
      cloned into a eukaryotic expression vector. The effect of the recombinant core
      protein on the transcriptional regulation of cellular as well as viral promoters
      was studied. Using transient transfection assay, our results demonstrated that
      the core protein can activate the promoter of human heat shock protein 70 gene,
      and suppressed the SV40 early promoter. These findings indicate that the core
      protein appears to function not only as a viral structural protein but also as a
      regulator of gene expression. The implications of core proteins on the viral
      maturation are discussed.

PMID- 9617771
TI  - Mapping of a type 1-specific and a type-common epitope on the E2 (gp53) protein
      of bovine viral diarrhea virus with neutralization escape mutants.
AB  - Bovine viral diarrhoea viruses (BVDV) have recently been segregated into two
      genotypes, BVDV 1 and BVDV 2. However, the antigenic differences and similarities
      of BVDV 1 and BVDV 2 remain poorly defined. In this study, the E2 epitopes of two
      neutralizing monoclonal antibodies (mAbs) produced against an isolate of BVDV 1
      were mapped. The mAb 157, previously determined to be broadly cross-reactive to
      BVDV, was discovered to be BVDV 1-specific, whereas mAb 348 bound to and
      neutralized BVDV 2. Both mAbs bound to epitopes within the first 192 amino acids
      of the E2 protein as determined by reactions with a C-terminally truncated E2. To
      identify critical amino acids affecting these epitopes, mAb escape mutants were
      selected for sequencing from BVDV 1 and BVDV 2 strains with different (wild-type)
      mAb binding phenotypes. In addition, the E2 gene of several BVDV were sequenced
      and the sequences were compared with amino acid changes in mutant viruses. Single
      nucleotide changes in escape mutants selected with mAb 157 resulted in deduced
      amino acid changes at E2 positions 9, 32 or 72. Amino acid changes at position 72
      also affected the epitope of mAb 348. Alignment of E2 nucleotide sequences
      revealed that BVDV 2 are missing six nucleotides encoding the equivalent of amino
      acids 31 and 32 of BVDV 1 and thus, this difference can account for the BVDV 1
      specificity of mAb 157. Single nucleotide mutations in mAb 348 escape mutants of
      BVDV 1 and BVDV 2 resulted in changes in 3 amino acids in the previously
      described immunodominant 71-74 region (Virology 190, 763-772). A fourth amino
      acid change observed in a mutant of BVDV 2 extended this region to position 77.
      Thus, the amino acid changes affecting the conserved epitope of mAb 348 occurred
      in a short spatial array over only seven amino acids, unlike the described
      composite epitopes previously mapped to this region.

PMID- 9617772
TI  - Bovine herpesvirus-1 infection affects the peptide transport activity in bovine
      cells.
AB  - Infection of cattle with bovine herpesvirus-1 (BHV-1) impairs the cell-mediated
      immune response (CMI) of the affected host. We investigated the location of
      interference of BHV-1 with the major histocompatibility complex (MHC) class I
      antigen presentation pathway by employing an assay that allows assessment of the
      peptide transport activity of the Transporter associated with Antigen
      Presentation (TAP) from the cytoplasm into the endoplasmic reticulum (ER). We
      found a considerable down-regulation of the peptide transport activity in bovine
      epithelial cells, taking place as early as 2 h after virus infection. This down
      regulation was also dose-dependent, and, at high multiplicities of infection
      (moi), led to an almost complete shutdown of TAP. By inhibiting peptide transport
      into the ER, the virus impairs loading of MHC class I molecules and their
      subsequent egress from the ER to the cell surface. This may lead to defective
      priming of cytotoxic T lymphocytes. Thus, BHV-1 is yet another member of its
      family Herpesviridae that selectively interferes with the host's antigen
      presentation machinery to evade the host's immune response in vivo.

PMID- 9617773
TI  - Nicotiana benthamiana plants transformed with the plum pox virus helicase gene
      are resistant to virus infection.
AB  - Nicotiana benthamiana Domin. plants were transformed with the cytoplasmic
      inclusion protein (CI) gene of plum pox potyvirus (PPV) to investigate, whether
      this non-structural protein would be able to confer resistance. The CI protein is
      an RNA helicase, which contains a conserved nucleotide binding motif (NTBM) and
      plays an important role in viral replication. Two gene constructions were
      developed for plant transformation. The first contains the original coding
      sequence of the CI gene under the control of 35S-promoter and nos terminator
      signal, the second is mutated in the NTBM region. Several transgenic plant lines
      were obtained following Agrobacterium tumefaciens-mediated transformation. The
      integration of the viral genes into the plant genome was confirmed using the
      polymerase chain reaction and the transgene derived mRNAs were detected by
      Northern blot hybridization. The CI protein in the transgenic plants could not be
      detected by Western blot analyses. One transgenic line containing the mutated CI
      gene remained completely symptomless after PPV infection, indicating that the
      putative defective helicase gene was capable of eliciting virus resistance.

PMID- 9617774
TI  - Atopic versus infectious diseases in childhood: a question of balance?
AB  - There is an increasing interest in the concept that respiratory tract infections
      during early childhood may in some circumstances confer protection against
      sensitisation to aeroallergens, via "bystander" stimulation of Th-1 associated
      immune functions in the regional lymph nodes draining the airway mucosa. We
      hypothesise below that this phenomenon may be but one component of a broader
      process operative during early postnatal life, in which generalised contact with
      the microbial environment plays an obligatory role in stimulating the functional
      maturation of the Th-1 arm of the immune response. We argue further that one of
      the most potent sources of such stimulation is provided by the normal commensal
      flora of the gastrointestinal tract, which is establish during early infancy.

PMID- 9617775
TI  - Natural history of soy allergy and/or intolerance in children, and clinical use
      of soy-protein formulas.
AB  - Atopic diseases of infants and children are common, debilitating, chronic and
      sometimes even life-threatening. Several well-conducted studies in high risk
      babies have demonstrated a significant reduction in the prevalence and severity
      of atopic diseases with dietary and environmental manipulations. The currently
      available cow's milk (CM) substitutes for infants are soy protein (SP) formulas
      (SPFs), hydrolyzed formulas (HF), and home-made meat-based formulas. Soybeans
      have been cultivated in Eastern countries for many centuries and were first used
      to feed US babies with CM allergy (CMA) in 1929. Since then, SPFs containing
      purified SP, a mixture of vegetable oils, and purified carbohydrate have been
      developed. From a nutritional point of view, SPFs are adequate, support normal
      growth, protein status, bone mineralization, are well accepted, and economical.
      SPFs are used for different conditions including CMA, lactose and galactose
      intolerance and in the management of severe gastroenteritis, and some studies
      show that feeding SPFs for the first six months of life significantly reduces the
      prevalence of atopic diseases in high risk babies. Although gastrointestinal
      symptoms and atopic dermatitis (AD) may occur in some SPF-fed children,
      anaphylaxis following the ingestion of soybean is extremely rare in children.
      However, in the past few years the antigenicity/allergenicity of SPFs has been
      over-emphasized in the medical literature. In this paper on the natural history
      of soy antigenicity/allergenicity we discuss all the pros and cons of SPFs, their
      composition and nutritional value, the basic immune definitions, chemistry and
      characterization of SPs. We then discuss the antigenicity and allergenicity of
      SPFs in animals, recent data on the use of SPFs and the incidence of soy allergy
      in children, clinical reactions to SPFs, and the clinical relevance of skin
      testing and IgE antibodies to soy, challenge test procedure, clinical indication
      of SPFs, and their relevance in the prevention of atopy. We have meta-analyzed 17
      different studies and conclude that history-based SPF allergy incidence totals
      27%, in skin prick tests (SPT) RAST-oral food challenge (OFC)/double-blind food
      challenge (DBFC)-based epidemiological studies attains 3%, and in challenge test
      studies 4%. We suggest that double-blind placebo-controlled food challenge
      (DBPCFC) studies in larger cohorts of babies may establish a more reliable
      prevalence of SPF allergy in different disorders associated with CMA.

PMID- 9617776
TI  - Validation of a rhinitis symptom questionnaire (ISAAC core questions) in a
      population of Swiss school children visiting the school health services. SCARPOL
      team. Swiss Study on Childhood Allergy and Respiratory Symptom with respect to
      Air Pollution and Climate. International Study of Asthma and Allergies in
      Childhood.
AB  - The primary aim of the study was to assess the validity of the ISAAC core
      questions on rhinitis in a population of Swiss school children by comparing them
      to skin prick test results. Second, the positive predictive value in detecting
      atopy among children with rhinitis symptoms was determined. Third, agreement
      between parental reports of hay fever and rhinitis symptoms was evaluated, since
      earlier Swiss prevalence surveys had exclusively relied on reported hay fever.
      MATERIAL AND METHODS: Two thousand nine hundred and fifty-four (81.2%) parents of
      7, 10 and 14-year old children filled in an exhaustive questionnaire which
      included the ISAAC core questions on rhinitis. Two thousand one hundred and
      twenty children also underwent skin prick testing against six common
      aeroallergens (grass mixture, birch, mugwort, D. pteronyssinus, cat and dog
      dander). The analysis is restricted to children with both questionnaire data and
      skin prick test results. RESULTS: Sensitization to any allergen was most strongly
      associated with reported hay fever (OR = 5.7, 95% CI 4.4-7.4), nose problems
      accompanied by itchy-watery eyes (OR = 4.4, 95% CI: 3.3-5.7), symptoms occurring
      only during pollen season (March through September) (OR = 4.9, 95% CI: 3.6-6.5)
      and a combination of these latter two symptoms (OR = 5.8, 95% CI: 4.1-8.1). The
      association was stronger for a sensitization to outdoor allergens than for indoor
      allergens. The specificity of the various questions was high, ranging from 77.5%
      to 97.6%, but the sensitivity was low (2.6% to 42.7%). The positive predictive
      value for atopy among children with symptoms was 63% for sneezing accompanied by
      itchy-watery eyes, 67% for symptoms occurring only during the pollen season and
      70% for reported hay fever. However, agreement between reported rhinitis symptoms
      and hay fever was only moderate. About one third of the children with symptoms
      indicative of seasonal rhinitis did not report the label "hay fever".
      CONCLUSIONS: We conclude from our analyses that the ISAAC core questions on
      rhinitis are highly specific and therefore useful in excluding atopy. In addition
      they have a high positive predictive value in detecting atopy among children with
      symptoms, but they are not helpful for detecting atopy in a general population of
      children (low sensitivity). To monitor time trends in the prevalence of allergic
      rhinitis in Switzerland, questions on rhinitis symptoms as well as on the
      diagnostic label "hay fever" have to be included in a questionnaire because they
      contain complementary information since under-diagnosis of allergic rhinitis is
      common.

PMID- 9617777
TI  - Immunoglobulin E and G antibodies two years after a booster dose of an aluminium
      adsorbed or a fluid DT vaccine in relation to atopy.
AB  - Immunoglobulin E and G levels to diphtheria and tetanus toxoids were investigated
      two years after a DT booster with either an adsorbed or a nonadsorbed, fluid
      vaccine, given at 10 years of age. Although IgE levels had declined, detectable
      IgE to diphtheria and tetanus toxoids were still found in 82% and 67% of samples,
      respectively, to be compared to prebooster levels of 3-14% and postbooster levels
      of 92-94%. The IgG levels had also declined but remained at equal and high levels
      in both the adsorbed and the fluid vaccine groups. The prevalence of allergic
      symptoms was similar in the two vaccination groups. Thus, the study showed an
      unexpected, long duration of the IgE responses elicited by a booster dose of DT
      vaccine. The booster dose also induced a durable, high IgG antibody response to
      both the adsorbed and the fluid vaccine.

PMID- 9617778
TI  - A reason why measures to avoid mite-induced asthma are more effective in children
      than in adults.
AB  - Mite-sensitive asthmatics seem to respond more markedly to a reduction in mite
      allergen in the bedding if they are children than if they are adults. In order to
      investigate this difference, 882 children who attended our allergy clinic were
      studied. The accompanying parents were asked standardized questions, and skin
      prick tests to Dermatophagoides pteronyssinus and D. farinae were performed on
      the children. The number of hours that the children spent in bed lessened
      progressively with increasing age, from a mean of 13.6 hrs. for 1 year olds to
      9.5 hrs for 17 yr olds: the mean for the total population was 12.0 hrs. This was
      significantly longer than the mean for the parents, 8.4 hrs (p=.000). It is
      likely that a longer period of exposure to mite allergen in bed is an important
      reason why children respond more markedly to avoidance measures in the bedroom
      than adults do.

PMID- 9617779
TI  - Correlation between Epstein Barr virus antibodies, serum IgE and atopic disease.
AB  - It is currently accepted that viral infections may influence the development of
      atopy. In the present study we evaluated serum IgE levels as well as the
      prevalence of symptoms indicative of atopic disease and EBV antibodies in 353
      children aged from 1 month to 19 years. Antibodies against EBV were detected by
      immunofluorescence. IgE levels in serum were measured by enzyme immunoassay.
      Dividing the study population according to EBV seropositivity and age, we noted
      that the prevalence of high IgE levels (> 2 s.d.) was, in total, more frequent in
      the EBV negative (32.9%) than in the positive subjects (27.6%). Interestingly,
      this higher prevalence was found only in the groups aged under six, especially in
      the 7 to 29 month group, where it was statistically significant (p=0.037),
      whereas in the 6-19 year group the situation was reversed. Furthermore, selecting
      only the atopic children younger than 3 years of age with high IgE levels and
      clinical symptoms of atopy (wheezing and/or dermatitis) it was possible to
      demonstrate lower EBV seropositivity compared with the normal IgE controls for
      each group, even though these differences were not statistically significant. In
      conclusion, the results of our study suggest that, in our selected population,
      EBV infection in the first years of life is associated with a lower prevalence of
      high IgE levels.

PMID- 9617780
TI  - Peripheral blood T and B lymphocyte subpopulations in infants with acute
      respiratory syncytial virus brochiolitis.
AB  - Most data concerning immunopathogenetic mechanisms involved in respiratory
      syncytial virus (RSV) infection are derived from animal studies. In infants with
      RSV bronchiolitis the target organ i.e. the airway is hard to explore. We looked
      for specific alterations in peripheral blood lymphocyte subpopulations in infants
      hospitalized for RSV bronchiolitis. Flow cytometric analysis with a large panel
      of monoclonals was performed on peripheral blood lymphocytes in thirty-two
      infants (mean age: 4.9 months) admitted for RSV bronchiolitis. Data collected on
      admission were compared with age-matched control values and also with results
      obtained at the end of the first week of hospitalization. Differences between age
      groups (older or younger than 4 months) and between clinical subgroups (clinical
      severity score more or less than 6) were looked for. In the group of infants as a
      whole, regardless of age and clinical score the number of CD4+ cells on admission
      was significantly elevated compared to normal values for age (p<.0001) including
      a high fraction of the naive suppressor-inducer subpopulation (CD4+/CD45RA+) and
      a low fraction of the reciprocal memory helper-inducer subpopulation
      (CD4+/CD29+). Within the CD8+ cell population the number of T cells with
      cytotoxic activity (CD8+/S6F1+) was significantly elevated (p<.0001) as were
      other types of cytotoxic cells. A significant decrease (p<.0001) in the
      proportion of the precursor/suppressor-effector subpopulation (CD8+/S6F1-) was
      seen. Absolute numbers and percentages of CD19+ B cells were significantly
      elevated (p<.0001) with a significant increase in the CD5+ subfraction (p<.0001)
      as well as in the CD10+ subfraction (p<.0001). In the older age group
      immunophenotypic cytotoxicity was more pronounced with increased clinical score.
      During recovery the CD45RA+:CD29+ ratio tended to normalize within the CD4+ T
      cells. Within the B lymphocyte subsets significant increase in the CD19+/CD5+
      fraction (p<.05) was seen. We conclude that there are significant changes in the
      number of peripheral blood lymphocyte subsets in infants with RSV bronchiolitis
      as compared to age-related controls. We hope that present data could be useful in
      further exploration of RSV immunology in humans. A possible link between RSV
      bronchiolitis and the subsequent development of atopy is mentioned.

PMID- 9617781
TI  - Life-threatening fish allergy successfully treated with immunotherapy.
AB  - Manifestations of fish allergy can include near-fatal anaphylactic reaction. In
      very sensitive patients, fish odors and cooking vapors may have some allergenic
      activity. We reported a case of life-threatening fish allergy in a girl of 39
      months referred for three episodes of Quincke edema with wheezing, cyanosis and
      severe urticaria after fish consumption or inhalation. Reagins were found against
      codfish and direct skin prick test with fresh food (codfish) showed important
      local reaction. Strict avoidance of fish in the diet is usually the only
      recommended procedure. However, in this particular case, the life-threatening
      nature of the allergic reaction was the major consideration to perform a
      desensitization. The child was treated by RUSH immunotherapy using codfish
      extracts from BENCARD company, following the schedule for insect venom allergy
      described by Pharmacia. Immunotherapy was performed immediately after
      determination of the threshold of sensitivity by specific skin prick tests and
      intra-dermal injections. Desensitization was initiated with a 1/10 dilution of
      the cut-off solution and 5 subcutaneous injections were administered daily. When
      important local reactions were observed, additional doses were necessary to
      obtain tolerance. After the RUSH therapy, the child was submitted to uncooked
      codfish odors without any reaction. No reaction has been observed even when the
      child has accidentally eaten a little piece of codfish.

PMID- 9617782
TI  - Association of HLA-DQ7 antigen with cow milk protein allergy in Italian children.
AB  - In this study we investigated the HLA association with cow milk allergy. Thirty
      seven Italian children with cow milk allergy and 35 randomly selected age-matched
      healthy children as control group were included in the study. DNA typing was
      performed by restriction fragment length polymorphism (RFLP) technique. We show
      the first statistically significant positive association between the expression
      of the HLA-DQ7 antigen and cow milk allergy. Several immunological tests (skin
      prick test, RIA, radioallergosorbent test (RAST) and ELISA) were performed to
      evaluate the humoral immune responses of DQ7 positive and DQ7 negative allergic
      patients. Our results show that among the DQ7 positive patients the majority
      presented a high humoral response. Furthermore, the in vitro proliferative
      response of patients to the beta-lactoglobulin antigen was performed to evaluate
      their cell-mediated immune response. We observed that the number of the
      nonresponders was higher in the DQ7 positive patients when compared to the DQ7
      negative patients. Our data indicate an association of HLA-DQ7 antigen with cow
      milk protein allergy and that the DQ7 positive patients had a prevalence of
      humoral rather than cellular responses.

PMID- 9617783
TI  - The effects of acute phencyclidine treatment on neuropeptide Y (NPY) neuronal
      system in the rat arcuate nucleus studied by immunocytochemistry and in situ
      hybridization.
AB  - Phencyclidine (PCP) is a dissociative drug and an antagonist of N-methyl-D
      aspartate (NMDA) receptor. The effects of PCP treatment on neuropeptide Y (NPY)
      system in the arcuate nucleus of the rat hypothalamus were examined both by
      immunocytochemistry and in situ hybridization. In acute PCP-treated rats, the NPY
      immunoreactive perikarya appeared in the arcuate nucleus but no perikarya were
      detected in controls, without colchicine pretreatment. The signals of NPY mRNA by
      in situ hybridization increased in the PCP-treated rats than those of controls.
      These results suggest that the NPY system in the arcuate nucleus might be partly
      controlled by glutamatergic neurons.

PMID- 9617784
TI  - Monoamines (norepinephrine, dopamine, serotonin) in the rat medial vestibular
      nucleus: endogenous levels and turnover.
AB  - Monoamine (norepinephrine, dopamine, serotonin) and metabolite endogenous levels
      were determined in the rat medial vestibular nucleus (MVN) using HPLC with
      electrochemical detection. As a comparison, the locus coeruleus (LC) and dorsal
      raphe nucleus (RD) which contain the cell bodies of MVN noradrenergic and
      serotoninergic neurons respectively were also analyzed. Norepinephrine (NE) and
      serotonin (5-HT) basal levels of MVN were high (33.8 and 39.2pmol/mg protein
      respectively) but lesser than in LC or RD. Great amounts of MHPG and 5-HIAA were
      also present in the MVN. The turnover of NE assessed both from the ratio MHPG/NE
      and by the decrease in the NE content after treatment with alpha
      methylparatyrosine was faster in the MVN (half-life: 1.5h) than in LC (half-life:
      3.6h). On the other hand, the ratio 5-HIAA/5-HT was lower in the MVN (0.58) than
      in the RD (0.85) indicating a smaller 5-HT turnover in the MVN. In addition, like
      LC and RD, the MVN contained meaningful amounts of dopamine (DA) and DOPAC. The
      high ratio DA/NE (0.27) suggests the presence of non precursor specific
      dopaminergic pools. However, individualized dopaminergic neurons have not yet
      been demonstrated. The data are discussed in line with the possible
      neurotransmitter function of monoamines in the MVN.

PMID- 9617785
TI  - Neurotransmission and the ontogeny of human brain.
AB  - The early appearance of neurotransmitters in brain tissue refers to their
      regulative functions on the neuronal circuits. Many neurotransmitters have direct
      effects on neuronal outgrowth and differentiation during brain development, which
      precede their role in synaptic information coding. Both the neurotrophic and
      neurotoxic properties of excitatory amino acids (EAAs) have focused special
      interest on glutamatergic neurotransmission during brain development. Therefore,
      this work intends to review and discuss developmental alterations of the EAA
      neurotransmitter system in the human brain, their relation to human brain
      maturation and implications for pathological processes during early human brain
      development.

PMID- 9617786
TI  - Salsolinol, catecholamine metabolites, and visual hallucinations in L-dopa
      treated patients with Parkinson's disease.
AB  - We could quantify the tetrahydroisoquinoline derivative salsolinol in urine of
      patients with Parkinson's disease and normal control subjects by means of high
      performance liquid chromatography and electrochemical detection. Urine levels of
      salsolinol were positively related to the homovanillic acid/3-O-methyl-dopa ratio
      in the cerebrospinal fluid that reflects dopamine metabolism. In the patient
      group with visual hallucinations, mean salsolinol level was significantly
      increased to almost the 3-fold of those found in patients without hallucinations.
      Since the daily L-dopa doses of both patient groups were nearly identical this
      result is not due to different L-dopa medications. Additionally, either high
      values of the main serotonin metabolite, 5-hydroxyindole acetic acid (HIAA) or
      the L-dopa/3-O-methyl-dopa ratio were found in cerebrospinal fluid of patients
      with hallucinations. The enhanced salsolinol levels in patients with visual
      hallucinations seem to be due to an overloaded dopaminergic pathway with an
      imbalance between dopaminergic and serotonergic systems. Thus, salsolinol appears
      as a predictor for hallucinosis in Parkinson's disease.

PMID- 9617787
TI  - Elevated 5-S-cysteinyldopamine/homovanillic acid ratio and reduced homovanillic
      acid in cerebrospinal fluid: possible markers for and potential insights into the
      pathoetiology of Parkinson's disease.
AB  - High-performance liquid chromatography with electrochemical detection has been
      employed to analyze ultrafiltrates of cerebrospinal fluid of Parkinson's Disease
      (PD) patients and age-matched controls for the dopamine (DA) metabolites
      homovanillic acid (HVA) and 5-S-cysteinyldopamine (5-S-CyS-DA). The mean level of
      HVA in the CSF of PD patients, measured 5 days after withdrawal from L-DOPA
      therapy, was significantly lower than that measured in controls. By contrast,
      mean levels of 5-S-CyS-DA were not significantly different in the CSF of PD
      patients taking L-DOPA (PD-LT patients) the same patients 5 days after
      discontinuing this drug (PD-LW patients) or controls. However, the mean 5-S-CyS
      DA/HVA concentration ratio was significantly (p < 0.05) higher in the CSF of PD
      LW patients compared to controls. Although the PD patient population employed in
      this study had been diagnosed with the disease several years previously and had
      been treated with L-DOPA for prolonged periods of time the results of this study
      suggest that low CSF levels of HVA and a high 5-S-CyS-DA/HVA ratio together might
      represent useful markers for early diagnosis of PD. The high 5-S-CyS-DA/HVA ratio
      observed in the CSF of PD-LW patients also provides support for the hypothesis
      that the translocation of glutathione or L-cysteine into neuromelanin-pigmented
      dopaminergic cell bodies in the substantia nigra might represent an early event
      in the pathogenesis of PD.

PMID- 9617788
TI  - Time and frequency domain analysis for the assessment of heart autonomic control
      in Parkinson's disease.
AB  - In order to evaluate autonomic regulation in Parkinson's disease, the heart-rate
      responses to passive head-up tilt and the spectral analysis of spontaneous heart
      rate variability in supine position were studied in 18 young (30.8 +/- 1.38 years
      old) and 13 aged (61.9 +/- 1.61 years) healthy controls and 13 patients with
      Parkinson's disease (62.9 +/- 1.55 years). Patients were evaluated in the
      University Hospital of the Canary Islands by a neurologist and a specialist in
      rehabilitation. Finally, a computerized procedure developed in the Dept. of
      Physiology of La Laguna University was used to quantify the autonomic regulation
      of heart-rate (HR) variability. In relation to the younger group, elderly
      controls showed a reduction in the amplitude and no differences in the latency of
      the three successive peaks of HR response to tilt. In relation to the elderly
      matched controls, the Parkinson group showed a slight decrease for the second
      response amplitude and no differences for both the first or third response
      amplitude and the latency of the three responses. In the frequency domain
      analysis of the spontaneous HR oscillation in supine position recording, the
      elderly and Parkinson groups showed a decrease in the power spectrum for low
      frequency (<0.04Hz; thermoregulation related band), mid frequency (0.04-0.15Hz;
      related to sympathetic activity in response to baroreceptors stimulation) and
      high frequency (0.15-0.4Hz; related to sympathovagal tonus activated by
      respiratory movements). In relation to elderly controls, the Parkinson group
      showed lower power in the three spectral bands studied. Present data support the
      hypothesis that both sympathetic and parasympathetic control of heart activity
      are impaired in Parkinson's disease and that this dysfunction can be assessed by
      combining time-domain and frequency-domain analysis of HR changes.

PMID- 9617789
TI  - Pattern of brain destruction in Parkinson's and Alzheimer's diseases.
AB  - Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common age
      related degenerative disorders of the human brain. Both diseases involve multiple
      neuronal systems and are the consequences of cytoskeletal abnormalities which
      gradually develop in only a small number of neuronal types. In AD, susceptible
      neurons produce neurofibrillary tangles (NFTs) and neuropil threads (NTs), while
      in PD, they develop Lewy bodies (LBs) and Lewy neurites (LNs). The specific
      lesional pattern of both illnesses accrues slowly over time and remains
      remarkably consistent across cases. In AD, six developmental stages can be
      distinguished on account of the predictable manner in which the neurofibrillary
      changes spread across the cerebral cortex. The pathologic process commences in
      the transentorhinal region (clinically silent stages I and II), then proceeds
      into adjoining cortical and subcortical components of the limbic system (stages
      III and IV - incipient AD), and eventually extends into association areas of the
      neocortex (stages V and VI - fully developed AD). During the course of PD,
      important components of the limbic system undergo specific lesions as well. The
      predilection sites include the entorhinal region, the CA2-sector of the
      hippocampal formation, the limbic nuclei of the thalamus, anterior cingulate
      areas, agranular insular cortex (layer VI), and - within the amygdala - the
      accessory cortical nucleus, the ventromedial divisions both of the basal and
      accessory basal nuclei, and the central nucleus. The amygdala not only generates
      important projections to the prefrontal association areas but also exerts
      influence upon all non-thalamic nuclei which in a non-specific manner project
      upon the cerebral cortex and upon the nuclei regulating endocrine and autonomic
      functions. All these amygdala-dependent structures themselves exhibit severe PD
      specific lesions. In general, the extranigral destructions are in themselves not
      sufficient to produce overt intellectual deterioration. Similarly, AD-related
      pathology up to stage III may be asymptomatic as well. Fully developed PD with
      concurring incipient AD, however, is likely to cause impaired cognition.
      Presently available data support the view that the occurrence of additional
      lesions in the form of AD stage III (or more) destruction is the most common
      cause of intellectual decline in PD.

PMID- 9617791
TI  - Increased density of entorhinal glutamate-immunoreactive vertical fibers in
      schizophrenia.
AB  - Gluatamtergic fibers have been immunocytochemically localized in the entorhinal
      cortex of postmortem schizophrenic brains. The density of small caliber vertical
      fibers was higher in schizophrenics than controls, with no significant increase
      in the number of large caliber fibers. Increased glutamatergic fiber density has
      been previously reported in the cingulate cortex. It is proposed that increases
      in glutamatergic fibers from the amygdala may be responsible for these changes
      and that they may play a central role in the pathophysiology of schizophrenia.

PMID- 9617792
TI  - Correlation between serum and urinary calcium levels and psychopathology in
      patients with affective disorders. Short communication.
AB  - To examine whether serum and urinary calcium levels were related to the
      psychopathology index (i.e. average score in clinically relevant scales of
      Minnesota Multiphasic Personality Inventory), 24 women aged 35.6 +/- 2.5 years
      and 20 men aged 34.3 +/- 2.1 years, suffering from affective disorders, were
      studied. A non-parametric bivariate correlation analysis revealed a negative
      correlation between PI and serum calcium (r = -0.256, p < 0.01), while urinary
      calcium levels correlated positively with PI (r = 0.236, p < 0.02). A positive
      correlation occurred between serum and urinary calcium (r = 0.968, p < 0.0001).
      When the data were analyzed by categorical classification of patients with normal
      or abnormal PI scores, serum calcium levels were smaller, and urinary calcium
      levels higher, in patients with abnormal PI (p < 0.01). The results support to
      the concept that alterations of calcium homeostasis occur in psychopathology.

PMID- 9617790
TI  - Platelet phenolsulphotransferase activity, monoamine oxidase activity and
      peripheral-type benzodiazepine binding in demented patients.
AB  - Blood platelet phenolsulphotransferase and monoamine oxidase activities, as well
      as platelet peripheral-type benzodiazepine binding have been studied in several
      neuropsychiatric disorders, in order to identify biochemical markers for altered
      brain functioning. In the present work, we determined platelet
      phenolsulphotransferase and monoamine oxidase activities in demented patients:
      they showed significantly higher phenolsulphotransferase and monoamine oxidase
      activities than controls. A significant positive correlation was found between
      enzyme activities and severity of illness. In the same subjects, we evaluated
      platelet peripheral-type benzodiazepine binding: a significant reduction of Bmax
      values was observed in demented patients, whereas Kd values did not substantially
      differ between the two subject groups. These findings are discussed with
      reference to central nervous system biochemical abnormalities of demented
      subjects: it may be that in Dementia of Alzheimer type either some central
      biochemical changes are reflected in certain peripheral tissues (such as
      platelets), or a systemic derangement occurs together with a cerebral
      involvement.

PMID- 9617793
TI  - Identification of a 37 kDa plant protein that interacts with the turnip mosaic
      potyvirus capsid protein using anti-idiotypic-antibodies.
AB  - Experimental data are provided for the presence of a plant protein that interacts
      with the capsid protein (CP) of turnip mosaic potyvirus (TuMV). The receptor-like
      protein was identified by exploiting the molecular mimicry potential of anti
      idiotypic antibodies. A single-chain Fv molecule derived from the monoclonal
      antibody 7A (Mab-7A), which recognizes the CP of TuMV, was produced in
      Escherichia coli and the recombinant protein was used to raise rabbit antibodies.
      The immune serum reacted with Mab-7A but not with a monoclonal antibody of the
      same isotype, indicating that anti-idiotypic antibodies were produced. These anti
      idiotypic antibodies recognized a 37 kDa protein from Lactuca sativa. Complex
      formation between the anti-idiotypic antibodies and the plant protein was
      inhibited by the CP of TuMV which indicates that the plant protein interacts with
      the viral protein. The 37 kDa protein was localized in chloroplasts and was
      detected in other plant species.

PMID- 9617794
TI  - Cloning, characterization and expression of carbonic anhydrase from the
      cyanobacterium Synechocystis PCC6803.
AB  - A 3.3 kb HindIII restriction-digest DNA fragment was isolated from a
      Synechocystis sp. strain PCC6803 subgenomic plasmid library which strongly
      hybridized to a 349 bp fragment of the icfA (ccaA) gene from Synechococcus sp.
      strain PCC7942. DNA sequence analysis of the fragment revealed three open reading
      frames (ORFs), two of which potentially coded for pantothenate synthetase
      (ORF275) and cytidylate kinase (ORF230). The third, ORF274, was 825 bp in length,
      encoding a deduced polypeptide of 274 aa (Mr, 30747) that bears 55% sequence
      identity to the Synechococcus icfA (ccaA) translation product, a beta-type
      carbonic anhydrase (CA). A 932 bp EcoRI fragment containing ORF274 was subcloned
      into an expression vector and the construct was transformed into Escherichia coli
      for overexpression. Electrometric assays for CA activity revealed that whole cell
      extracts containing the recombinant protein significantly enhanced the rate of
      conversion of CO2 to HCO3- and that 98% of this catalytic activity was inhibited
      by ethoxyzolamide, a well-characterized CA inhibitor. Antisera derived against
      the overexpressed protein recognized a 30.7 kDa protein that was predominantly
      associated with the isolated carboxysome fraction from Synechocystis. These
      results provide molecular and physiological evidence for the identification of a
      ccaA homologue in Synechocystis PCC6803 that encodes a carboxysomal beta-type CA.

PMID- 9617795
TI  - A light-independent developmental mechanism potentiates flavonoid gene expression
      in Arabidopsis seedlings.
AB  - Throughout the plant kingdom expression of the flavonoid biosynthetic pathway is
      precisely regulated in response to developmental signals, nutrient status, and
      environmental stimuli such as light, heat and pathogen attack. Previously we
      showed that, in developing Arabidopsis seedlings, flavonoid genes are transiently
      expressed during germination in a light-dependent manner, with maximal mRNA
      levels occurring in 3-day-old seedlings. Here we describe the relationship
      between developmental and environmental regulation of flavonoid biosynthesis by
      examining phenylalanine ammonia-lyase (PAL), chalcone synthase (CHS), chalcone
      isomerase (CHI), and dihydroflavonol reductase (DFR) mRNA levels in germinating
      Arabidopsis seedlings as a function of light, developmental stage and
      temperature. We show that seedlings exhibit a transient potential for induction
      of these four genes, which is distinct from that observed for chlorophyll a/b
      binding protein(CAB). The potential for flavonoid gene induction was similar in
      seedlings grown in darkness and red light, indicating that induction potential is
      not linked to cotyledon expansion or the development of photosynthetic capacity.
      The evidence for metabolic regulation of flavonoid genes during seedling
      development is discussed.

PMID- 9617796
TI  - RNA editing in gymnosperms and its impact on the evolution of the mitochondrial
      coxI gene.
AB  - Sequence analysis of the mitochondrial coxI gene in eight gymnosperm species
      revealed a high rate of nonsynonymous nucleotide substitutions with a strong
      (98%) predominance of C-T substitutions. Further analysis of the corresponding
      coxI cDNA sequences showed that all the non-synonymous C-T changes in the coxI
      genomic DNA sequences were eliminated by RNA editing resulting in nearly
      identical mRNA (amino acid) sequences among the species. Pronounced variation in
      the number and location of edited sites was found among species. Most species had
      a relatively large number of edited sites (from 25 to 34). However, no RNA
      editing of the coxI sequence was found in Gingko biloba or Larix sibirica. The
      sequence composition of the investigated coxI fragment suggests that the coxI
      gene in G. biloba and L. sibirica originated from edited mitochondrial coxI
      transcripts by reverse transcription followed by insertion into the nuclear
      genome or back into the mitochondrial genome. Our results also demonstrate that
      where there are a large number of edited sites, RNA editing can accelerate the
      divergence of nucleotide sequences among species.

PMID- 9617797
TI  - Abundance of mRNAs encoding HMG1/HMG2 class high-mobility-group DNA-binding
      proteins are differentially regulated in cotyledons of Pharbitis nil.
AB  - The abundance of an mRNA encoding an HMG 1/2 protein from Pharbitis nil (HMG1)
      has been previously shown to be regulated by light and an endogenous rhythm in
      cotyledons. A second Pharbitis nil HMG cDNA (HMG2) was characterized. The
      sequence of HMG2 was 82% and 86% identical to HMG1 at the nucleotide and amino
      acid level, respectively. As with HMG1, HMG2 mRNA was detected in all vegetative
      tissues and was most abundant in roots. However, unlike HMG1, HMG2 mRNA abundance
      did not increase upon transfer of cotyledons to darkness and did not exhibit
      regulation by an endogenous circadian rhythm when maintained in continuous
      darkness over a 68 h period. Similarly, while the abundance of HMG1 mRNA during a
      dark period that induced photoperiodically controlled flowering was dramatically
      affected by brief light exposure (night break), this treatment had no effect on
      HMG2 mRNA abundance. Collectively, these data are consistent with a role of HMG1
      in contributing to the circadian-regulated and/or dark-regulated gene expression
      with constitutive expression of HMG2 playing a housekeeping role in the general
      regulation of gene expression in Pharbitis nil cotyledons.

PMID- 9617798
TI  - Alternative splicing of a precursor-mRNA encoded by the Chlorella sorokiniana
      NADP-specific glutamate dehydrogenase gene yields mRNAs for precursor proteins of
      isozyme subunits with different ammonium affinities.
AB  - Chlorella sorokiniana has seven ammonium-inducible, chloroplastic NADP-specific
      glutamate dehydrogenase (NADP-GDH) isozymes composed of varying ratios of alpha-
      and beta-subunits. Southern blot and allele-specific PCR analyses indicate that
      the C. sorokiniana genome possesses a single 7178 bp nuclear NADP-GDH gene. cDNA
      cloning and sequencing, 5'-RACE-PCR analysis, and RNase protection analysis
      identified two NADP-GDH mRNAs that are identical with the exception of a 42 nt
      sequence located within the 5'-coding region of the longer mRNA. The 42 nt
      sequence, termed an auxon because it serves as an exon or intron, appears to
      undergo alternative splicing from the precursor mRNA by a process that is
      regulated by both nutritional and environmental signals. Depending upon whether
      the auxon is included or excluded in a mature mRNA, the gene can be considered to
      consist of 22 or 23 exons, respectively. The 2074 and 2116 nt mRNAs encode
      precursor proteins of 56,350 and 57,850 Da, respectively. The N-termini of the
      purified mature alpha- and beta-subunits were sequenced, identifying full-length
      subunits of 53,501 and 52,342 Da, respectively. The sequences of the subunits are
      identical except for an 11 amino acid extension at the N-terminus of the alpha
      subunit. The alpha-subunit has an additional alpha-helical domain at its N
      terminus compared with the beta-subunit. By correlating the abundances of the two
      mRNAs with the levels (and relative turnover rates) of the alpha- and beta
      subunit antigens during induction in Chlorella, the larger mRNA is proposed to
      encode the larger subunit.

PMID- 9617800
TI  - Functional analysis of the promoter region of a maize (Zea mays L.) H3 histone
      gene in transgenic Arabidopsis thaliana.
AB  - A 1023 bp fragment and truncated derivatives of the maize (Zea mays L.) histone
      H3C4 gene promoter were fused to the beta-glucuronidase (GUS) gene and introduced
      via Agrobacterium tumefaciens into the genome of Arabidopsis thaliana. GUS
      activity was found in various meristems of transgenic plants as for other plant
      histone promoters, but unexplained activity also occurred at branching points of
      both stems and roots. Deletion of the upstream 558 bp of the promoter reduced its
      activity to an almost basal expression. Internal deletion of a downstream
      fragment containing plant histone-specific sequence motifs reduced the promoter
      activity in all tissues and abolished the expression in meristems. Thus, both the
      proximal and distal regions of the promoter appear necessary to achieve the final
      expression pattern in dicotyledonous plant tissues. In mesophyll protoplasts
      isolated from the transformed Arabidopsis plants, the full-length promoter showed
      both S phase-dependent and -independent activity, like other plant histone gene
      promoters. Neither of the 5'-truncated nor the internal-deleted promoters were
      able to direct S phase-dependent activity, thus revealing necessary cooperation
      between the proximal and distal parts of the promoter to achieve cell cycle
      regulated expression. The involvement of the different regions of the promoter in
      the different types of expression is discussed.

PMID- 9617799
TI  - Induction of a beta-phaseolin promoter by exogenous abscisic acid in tobacco:
      developmental regulation and modulation by external sucrose and Ca2+ ions.
AB  - Phaseolin genes are induced by unidentified factors at the onset of seed
      maturation in embryos of both Phaseolus and tobacco. We show that in tobacco,
      expression of a beta-phaseolin promoter-GUS (PHSbeta-uidA) mRNA and the
      corresponding GUS activity, could be induced by abscisic acid (ABA). The effect
      paralleled an increase in the amount of endogenous 12S globulin (Glb12S) mRNA. In
      contrast, ABA repressed the expression of isocitrate lyase (ll9) mRNA. The
      responses of PHSbeta-uidA and Glb12S to ABA declined markedly between 11 and 13
      DAF, indicating that they are developmentally regulated. We also show evidence
      that the ABA response of PHSbeta-uidA can be modulated by the external
      concentrations of sucrose and Ca2+ ion. These compounds inhibited the response if
      added to the medium separately, in the concentration ranges of 80-200 mM for
      sucrose and 0.76-20 mM for CaCl2. However, the presence of both sucrose and CaCl2
      restored the ABA response to 20-40% of the maximum value measured in sucrose- and
      CaCl2-free media. These results suggest that ABA induction of beta-phaseolin gene
      expression is modulated by developmental signals and by the external supply of
      sucrose and calcium to the embryos.

PMID- 9617801
TI  - The xylose isomerase gene from Thermoanaerobacterium thermosulfurogenes allows
      effective selection of transgenic plant cells using D-xylose as the selection
      agent.
AB  - The xylose isomerase gene (xylA) from Thermoanaerobacterium thermosulfurogenes
      (formerly Clostridium thermosulfurogenes) has been expressed in three plant
      species (potato, tobacco, and tomato) and transgenic plants have been selected on
      xylose-containing medium. The xylose isomerase gene was transferred to the target
      plant by Agrobacterium-mediated transformation. The xylose isomerase gene was
      expressed using the enhanced cauliflower mosaic virus (CaMV) 35S promoter and the
      omega' translation enhancer sequence from tobacco mosaic virus. Unoptimized
      selection studies showed that, in potato and tomato, the xylose isomerase
      selection was more efficient than the established kanamycin resistance selection,
      whereas in tobacco the opposite was observed. Efficiency may be increased by
      optimization. The xylose isomerase system enables the transgenic cells to utilize
      xylose as a carbohydrate source. It is an example of a positive selection system
      because transgenic cells proliferate while non-transgenic cells are starved but
      still survive. This contrasts to antibiotic or herbicide resistance where
      transgenic cells survive on a selective medium but non-transgenic cells are
      killed. The results give access to a new selection method which is devoid of the
      disadvantages of antibiotic or herbicide selection.

PMID- 9617802
TI  - Structure, expression and localization of a germin-like protein in barley
      (Hordeum vulgare L.) that is insolubilized in stressed leaves.
AB  - The primary leaves of young barley seedlings contain two major, extracellular,
      acid-soluble proteins of ca. 22 and 23 kDa apparent molecular mass. These
      proteins disappeared from the intercellular washing fluid upon stress treatments
      that enhanced H2O2 levels and that induced resistance to subsequent challenge by
      the powdery mildew fungus Erysiphe graminis f. sp. hordei. A partial peptide
      sequence of the 22 kDa protein was determined, and a cDNA clone was isolated. The
      22 kDa protein belongs the the group of germin-like proteins (GLPs) and was
      designated HvGLP1. Despite its similarity to germin, i.e. oxalate oxidase, no
      oxalate oxidase activity of HvGLP1 could be detected. The RNA and soluble protein
      of HvGLP1 was highly abundant in young leaves, less abundant in older leaves and
      absent in roots. HvGLP1 RNA oscillated with a circadian rhythm, the minimum and
      maximum of RNA abundance being at the end of the dark and light periods,
      respectively. Heat and H2O2 treatment as well as pathogen infection caused
      disappearance of HvGLP1 protein from the fraction of soluble proteins of the
      intercellular space. HvGLP1 protein could be re-solubilized from cell walls of
      heat- or H2O2-treated leaves by boiling in SDS suggesting non-covalent cross
      linking. Although a physiological role of HvGLP1 insolubilization is still open,
      the protein may serve as marker for oxidative stress in cereals.

PMID- 9617803
TI  - The gene encoding T protein of the glycine decarboxylase complex involved in the
      mitochondrial step of the photorespiratory pathway in plants exhibits features of
      light-induced genes.
AB  - We have isolated and characterized a genomic clone encoding the 41 kDa monomer T
      protein. This gene called gdcT spans approximately 3 kbp and is composed of four
      exons interrupted by three introns (321, 691 and 114 bp). The splice sites for
      donor and acceptor are in agreement with the canonical GT/AG rule. Primer
      extension strongly suggests the presence of two major transcription start sites.
      The first transcription start site around 43 bases downstream of a putative TATA
      box was assigned the +1 position. The second (+31) is not correlated with a
      putative TATA box, but revealed a pyrimidine-rich region which is very similar to
      the initiator element. Sequence analysis of the 5'-upstream region of the gene
      reveals three consensus regions found in the nuclear genes encoding the
      chloroplastic proteins of ribulose-1,5-bisphosphate carboxylase (rbcS) and the
      chlorophyll a/b-binding protein (cab) such as an AT-rich sequence localized at 
      539 to -530, a box II core sequence GGTTAA (-123 to -118) and between -364 and 
      354 a tandem GATA motif. These elements are known to be involved respectively in
      the regulation of light-responsiveness and cell-type specificity expression of
      plant genes. Gel shift assays indicate that the box II core sequence could bind
      protein nuclear factors similar to the trans-acting factor which interact with
      corresponding promoter region of rbcS gene.

PMID- 9617804
TI  - The molecular basis of C4 photosynthesis in sorghum: isolation, characterization
      and RFLP mapping of mesophyll- and bundle-sheath-specific cDNAs obtained by
      differential screening.
AB  - C4 photosynthesis depends upon the strict compartmentalization of the CO2
      assimilatory enzymes of the C4 and Calvin cycle in two different cell types,
      mesophyll and bundle-sheath cells. A differential accumulation is also observed
      for enzymes of other metabolic pathways, and mesophyll and bundle-sheath
      chloroplasts of NADP-malic enzyme type C4 plants differ even in their
      photosynthetic electron transport chains. A large number of studies indicate that
      this division of labour between mesophyll and bundle-sheath cells is the result
      of differential gene expression. To investigate the extent of this differential
      gene expression and thus gain insight into the genetic basis of C4
      photosynthesis, genes that are differentially expressed in the mesophyll and
      bundle-sheath cells were catalogued in the NADP-malic enzyme type C4 grass
      Sorghum bicolor. A total of 58 cDNAs were isolated by differential screening.
      Using a tenfold difference in transcript abundance between mesophyll and bundle
      sheath cells as a criterion, 25 cDNAs were confirmed to encode mesophyll-specific
      gene sequences and 8 were found to encode bundle-sheath-specific sequences. Eight
      mesophyll-specific cDNAs showed no significant similarities within GenBank and
      may therefore represent candidates for the elucidation of hitherto unknown
      functions in the differentiation of mesophyll and bundle-sheath cells. The
      chromosomal location of 50 isolated cDNAs was determined by RFLP mapping using an
      interspecific sorghum cross.

PMID- 9617805
TI  - Engineering in vivo instability of firefly luciferase and Escherichia coli beta
      glucuronidase in higher plants using recognition elements from the ubiquitin
      pathway.
AB  - The ubiquitin pathway targets proteins for degradation through the post
      translational covalent attachment of the 76 amino acid protein ubiquitin to
      epsilon-amino lysyl groups on substrate proteins. Two instability determinants
      recognized by the ubiquitin pathway in Saccharomyces cerevisiae have been
      identified. One is described by the N-end rule and requires specific
      destabilizing residues at the substrate protein N-termini along with a proximal
      lysyl residue for ubiquitin conjugation. The second is a linear uncleavable N
      terminal ubiquitin moiety. The ability of these two determinants to function in
      higher plants was investigated in tobacco protoplast transient transfection
      assays using DNA encoding variants of well characterized reporter enzymes as
      substrates: firefly luciferase that is localized to peroxisomes (pxLUC), a
      cytosolic version of LUC (cLUC), and Escherichia coli beta-glucuronidase (GUS).
      cLUC with phenylalanine encoded at its mature N-terminus was 10-fold less
      abundant than cLUC with methionine at its mature N-terminus. GUS with
      phenylalanine encoded at its mature N-terminus was 3-fold less abundant than GUS
      with methionine at its mature N-terminus. The presence of a uncleavable N
      terminal ubiquitin fusion resulted in 50-fold lower protein accumulation of cLUC,
      but had no effect on GUS. Both instability determinants had a much larger effect
      on cLUC than on pxLUC, suggesting that these degradation signals are either
      unrecognized or poorly recognized in the peroxisomes.

PMID- 9617806
TI  - A model for RNA-mediated gene silencing in higher plants.
AB  - Homology-dependent gene silencing (HdGS) which is the generic term for
      transcriptional gene silencing (TGS), post-transcriptional gene silencing (PTGS)
      and RNA-mediated virus-resistance (RmVR) has been shown to frequently occur in
      transgenic plants. The role of RNA as a target and initiator of PTGS and RmVR is
      more and more manifested. Because TGS is assumed to be induced by a DNA-DNA
      interaction-mediated promoter methylation, a possible involvement of RNA in TGS
      was not really considered up to now. In this review we attempt to demonstrate
      that all three types of HdGS could be triggered by one RNA-based mechanism. A
      model proposing TGS as a consequence of RNA-directed DNA methylation (RdDM) and a
      refined mRNA threshold mechanism are presented. In contrast to the view that high
      amounts of mRNA are required we assume that the concentration of RNAs that can
      serve as efficient templates for a plant-encoded RNA-directed RNA polymerase
      (RdRP) plays a key role in HdGS and possibly also in natural gene regulation of
      non-transformed cells. According to this idea a particular information must be
      encoded to render mRNA turn-over products a suitable RdRP substrate. It will be
      discussed that such a mechanism could account for the silencing phenomena of
      poorly transcribed transgenes. Finally, an explanation for the coherency between
      PTGS and DNA methylation is documented.

PMID- 9617807
TI  - Structure and evolution of Cyclops: a novel giant retrotransposon of the
      Ty3/Gypsy family highly amplified in pea and other legume species.
AB  - We characterized a novel giant Gypsy-like retrotransposon, Cyclops, present in
      about 5000 copies in the genome of Pisum sativum. The individual element Cyclops
      2 measures 12 314 bp including long terminal repeats (LTRs) of 1504 bp and 1594
      bp, respectively, showing 4.1% sequence divergence between one another. Cyclops-2
      carries a polypurine tract (PPT) and an unusual primer binding site (PBS)
      complementary to tRNA-Glu. The element is bounded by 5 bp target site
      duplications and harbors three successive internal regions with homology to
      retroviral genes gag (424 codons) and pol (1382 codons) and an additional open
      reading frame (423 codons) of unknown function indicating the element's potential
      capacity for gene transduction. The pol region contains sequence motifs related
      to the enzymes protease, reverse transcriptase, RNAse H and integrase in the same
      typical order (5'-PR-RT-RH-IN-3') known for retroviruses and Gypsy-like
      retrotransposons. The reading frame of the pol region is disrupted by several
      mutations suggesting that Cyclops-2 does not encode functional enzymes. A
      phylogenetic analysis of the reverse transcriptase domain confirms our
      differential genetic assessment that Cyclops from pea is a novel element with no
      specific relationship to the previously described Gypsy-like elements from
      plants. Genomic Southern hybridizations show that Cyclops is abundant not only in
      pea but also in common bean, mung bean, broad bean, soybean and the pea nut
      suggesting that Cyclops may be an useful genetic tool for analyzing the genomes
      of agronomically important legumes.

PMID- 9617808
TI  - A new homeodomain-leucine zipper gene from Arabidopsis thaliana induced by water
      stress and abscisic acid treatment.
AB  - We report the isolation and characterization of a new homeobox gene from
      Arabidopsis thaliana using a polymerase chain reaction (PCR) cloning strategy.
      The full-length cDNA, designated Athb-12, encodes a protein of 235 amino acids.
      It contains the conserved DNA binding domain and the leucine zipper motif,
      characteristic of the homeodomain-leucine zipper family of transcription factors.
      The deduced amino acid sequence of Athb-12 shows over 80% identity to the
      Arabidopsis Athb-7 in the homeodomain (82%) and the leucine zipper motif (80%) of
      the proteins. However, outside the homeodomain and the leucine zipper motif, the
      homology is significantly lower. RNA analysis identified only one 0.96 kb
      transcript consistent with the size of Athb-12 cDNA. The Athb-12 transcript was
      detected in stem, leaf, flower and root as well as in seedlings. Treatment with
      water stress and exogenous abscisic acid (ABA) resulted in the accumulation of
      Athb-12 mRNA, similar to that of Athb-7. However, the time course of the Athb-12
      response to ABA differed from that of Athb-7, suggesting that both genes, in
      response to ABA, are regulated in different manners. Taken together, these data
      suggest that Athb-12 and Athb-7 are members of a related gene family involved in
      the plant's response to water stress.

PMID- 9617810
TI  - Regulation of abscisic acid-induced transcription.
AB  - The phytohormone abscisic acid is probably present in all higher plants. This
      hormone is necessary for regulation of several events during seed development and
      for the response to environmental stresses such as desiccation, salt and cold. An
      important part of the physiological response to abscisic acid is achieved through
      gene expression. Here, we summarize the current knowledge of regulation of
      abscisic acid-induced transcription. The main focus is on a description of the
      known abscisic acid-responsive cis-elements, their properties and the possible
      transacting factors binding to the elements. Results have shown that cooperative
      action of cis-elements and the promoter configuration is crucial for regulation
      by abscisic acid. Furthermore, several elements are organ- and species-specific.
      Recent studies of the chromatin structure of abscisic acid-responsive genes point
      to the importance of induction of transcription by coactivators or by
      phosphorylation/dephosphorylation of transcription factors. An interesting
      example of activation by a cofactor is the cooperative action between abscisic
      acid-signaling and the regulatory protein Viviparous 1 through the abscisic acid
      responsive element.

PMID- 9617809
TI  - Identification of new early auxin markers in tobacco by mRNA differential
      display.
AB  - Differential display of mRNA has been improved by developing a two-step PCR
      amplification procedure. The modified differential display has been applied to
      identify early alterations of mRNA expression in response to auxin treatment of
      tobacco seedlings. This approach has led to the isolation of four fragments
      corresponding to auxin-up-regulated mRNAs. One, named GO15-13, shows significant
      homology with the 3' end of the coding region of the soybean SAUR X10A. The three
      other fragments present no homology with sequences available in the databases and
      constitute potential new early auxin markers.

PMID- 9617811
TI  - Cytokinin regulates the expression of a soybean beta-expansin gene by a post
      transcriptional mechanism.
AB  - The cytokinin-inducible soybean mRNA Cim1 accumulates 20-60-fold upon cytokinin
      addition to cytokinin-starved soybean suspension cultures. In this report, we
      demonstrate that cytokinin-induced stability of the Cim1 mRNA plays an important
      role in the accumulation of the message. We also present evidence that cytokinin
      induced Cim1 stability is blocked by the addition of the protein phosphatase
      inhibitor okadaic acid. Thus, we suggest that protein phosphatase activity is
      required for the cytokinin-induced stability and subsequent accumulation of Cim1
      in soybean cells. The deduced amino acid sequence of the Cim1 protein product is
      similar to the group I pollen allergens from various plants, which constitute a
      subfamily of expansin proteins. The relatedness between Cim1 and the expansins
      supports our hypothesis that the protein product of Cim1 is localized to the cell
      wall and suggests a role for Cim1 in cytokinin-regulated cell wall expansion.
      Thus, post-transcriptional regulation of Cim1 by cytokinin may represent a
      molecular link between cytokinin and changes in cell shape and size.

PMID- 9617812
TI  - Differential expression of senescence-associated mRNAs during leaf senescence
      induced by different senescence-inducing factors in Arabidopsis.
AB  - Four cDNA clones, named pSEN2, pSEN3, pSEN4, and pSEN5, for mRNAs induced during
      leaf senescence in Arabidopsis thaliana were characterized. The clones were
      isolated from a cDNA library of detached leaves incubated in darkness for 2 days
      to accelerate senescence, first by differential screening and then by examining
      expression of the primarily screened clones during age-dependent leaf senescence.
      Transcript levels detected by these cDNA clones, thus, were up-regulated in an
      age-dependent manner and during dark-induced leaf senescence. In contrast, when
      leaf senescence was induced by ethylene, ABA or methyljasmonate, the transcript
      level detected by the clones was differentially regulated depending on the
      senescence-inducing hormones. The transcript level for pSEN4 increased during
      senescence induced by all three hormones, while the transcript detected by the
      pSEN2 clone did not increase during senescence induced by ethylene. The
      transcript level for pSEN5 was increased upon ABA-induced senescence but
      decreased during ethylene-induced senescence. The pSEN3 clone detected multiple
      transcripts that are differentially regulated by these factors. The results show
      that, although the apparent senescence symptoms of Arabidopsis leaf appear
      similar regardless of the senescence-inducing factors, the detailed molecular
      state of leaf cells during senescence induced by different senescence-inducing
      factors is different. The pSEN3 clone encodes a polyubiquitin and the pSEN4 clone
      encodes a peptide related to endoxyloglucan transferase. This result is
      consistent with the expected roles of senescence-induced genes during leaf
      senescence.

PMID- 9617813
TI  - A comparison of the expression patterns of several senescence-associated genes in
      response to stress and hormone treatment.
AB  - The expression of several Arabidopsis thaliana senescence-associated genes (SAGs)
      in attached and/or detached leaves was compared in response to age, dehydration,
      darkness, abscisic acid, cytokinin, and ethylene treatments. Most of the SAGs
      responded to most of the treatments in a similar fashion. Detachment in darkness
      and ethylene were the strongest inducers of both SAGs and visible yellowing.
      Detachment in light was also a strong inducer of SAGs, but not of visible
      yellowing. The other treatments varied more in their effects on individual SAGs.
      Responses were examined in both older and younger leaves, and generally were much
      stronger in the older ones. Individual SAGs differed from the norms in different
      ways, however, suggesting that their gene products play a role in overlapping but
      not identical circumstances. Some SAGs responded quickly to treatments, which may
      indicate a direct response. Others responded more slowly, which may indicate an
      indirect response via treatment-induced senescence. Four new SAGs were isolated
      as part of this work, one of which shows strong similarity to late embryogenesis
      abundant (Lea) genes.

PMID- 9617814
TI  - Molecular cloning and chromosomal mapping of type one serine/threonine protein
      phosphatases in Arabidopsis thaliana.
AB  - Type one serine/threonine protein phosphatases (PP1s) have been implicated in
      various processes of plant growth and development. In all plant species studied,
      PP1s are encoded by multigene families. Previous studies in our laboratory
      identified five Arabidopsis thaliana PP1 genes (TOPP1, TOPP2, TOPP3, TOPP4 and
      TOPP5). In the present study, we report the isolation of three additional PP1
      genes (TOPP6, TOPP7 and TOPP8). Southern blot analyses indicate that these three
      newly isolated genes are single-copy genes in A. thaliana genome. All the three
      genes are expressed in roots, rosettes and flowers, although their expression
      levels appear to be lower than those of the five previously identified TOPP
      genes. Six of the eight TOPP genes were mapped to different positions on four of
      five A. thaliana chromosomes. Sequence comparison revealed that TOPP genes belong
      to different subgroups of plant PP1 genes, suggesting that they may encode
      proteins with distinct functions.

PMID- 9617815
TI  - Phenotypic analysis and molecular cloning of discolored-1 (dsc1), a maize gene
      required for early kernel development.
AB  - Recessive mutations in the maize dsc1 locus prevent normal kernel development.
      Solidification of the endosperm in homozygous dsc1- mutant kernels was
      undetectable 12 days after pollination, at which time the tissue was apparently
      completely solidified in wild-type kernels. At later times endosperm did solidify
      in homozygous dsc1- mutant kernels, but there was a marked reduction in the
      volume of the tissue. Embryo growth in homozygous dsc1- kernels was delayed
      compared to wild-type kernels, but proceeded to an apparently normal stage 1 in
      which the scutellum, coleoptile, and shoot apex were clearly defined. Embryo
      growth then ceased and the embryonic tissues degraded. Late in kernel development
      no tissue distinctions were obvious in dsc1- mutant embryos. Immature mutant
      embryos germinated when transplanted from kernels to tissue culture medium prior
      to embryonic degeneration, but only coleoptile proliferation was observed. The
      dsc1 gene was isolated by transposon tagging. Analysis of the two different dsc1-
      mutations confirmed that transposon insertion into the cloned genomic locus was
      responsible for the observed phenotype. Dsc1 mRNA was detected specifically in
      kernels 5-7 days after pollination. These data indicate Dsc1 function is required
      for progression of embryo development beyond a specific stage, and also is
      required for endosperm development.

PMID- 9617816
TI  - Biochemical and immunological characterization of rice homologues of the human
      immunodeficiency virus-1 Tat binding protein and subunit 4 of human 26S
      proteasome subunits.
AB  - Previously, we isolated two cDNA clones, TBPOs-1 and TBPOs-2, encoding putative
      ATPases that are the rice homologues of human immunodeficiency virus-1 (HIV-1)
      Tat binding protein-1 and subunit 4 of human 26S proteasome. In order to
      determine the RNA-dependent ATPase activity of these putative proteins, the
      subclones from these cDNA clones were expressed in Escherichia coli as fusion
      proteins with maltose-binding protein. The recombinant proteins stimulated ATP
      hydrolysis in the presence of poly(U) and rice total RNA. In contrast, single-
      and double-stranded forms of HindIII-digested lambda phage DNA are less effective
      at stimulating ATP hydrolysis. Western blot analysis using antisera against the
      TBPOs proteins showed a widespread appearance of these proteins in rice tissues
      and cultured cells. The TBPOs proteins were also found around the region where
      rice proteasomes would sediment. In addition, the TBPOs-1 protein bound to
      tobacco TATA-binding protein in vitro. Thus, we suggest that the TBPOs proteins
      are novel RNA-dependent ATPases characteristic of DEAD-box proteins and propose
      that the TPBOs proteins can exist in rice proteasomes. Further, the TBPOs-1
      protein is thought to play a role in transcriptional events.

PMID- 9617817
TI  - Molecular cloning and characterization of starch-branching enzyme II from potato.
AB  - Full-length cDNA for starch branching enzyme (SBE) II of potato was isolated and
      sequenced. In potato, similarly to most other investigated plants, the SBE-II
      isoform differs from SBE-I by having an acidic amino-terminal extension and a
      shorter carboxyterminus. Two forms of SBE-II, migrating as 98 and 95 kDa proteins
      in 6% SDS-polyacrylamide gels, were associated to tuber starch. The latter form
      was 16 amino acids shorter in the amino terminus. Transcript of SBE-II was
      present in leaf tissue, whereas significant expression was not seen in tubers. On
      the other hand, a significant amount of SBE-I transcript was detected in tuber
      tissue but not in leaves.

PMID- 9617818
TI  - HSP 12 is a LEA-like protein in Saccharomyces cerevisiae.
AB  - LEA group I, II and III antibodies all recognised soluble proteins present in an
      extract of yeast (Saccharomyces cerevisiae). The smaller protein of the two
      recognised by the group I antibody displayed identical migration on SDS-PAGE to
      the pea seed LEA group I protein against which the antibody was raised. However,
      the antibody failed to recognise the predominant protein present after heating
      the extract at 80 degrees C for 10 min. This predominant protein, which also
      displayed identical migration on SDS-PAGE, was purified from the supernatant of
      the extract heated at 80 degrees C for 10 min. Peptide sequencing after CNBr
      cleavage identified the isolated protein as the heat shock protein HSP 12.
      Despite a previous report that HSP 12 is a heat shock protein, HSP 12 was found
      to increase in yeast grown at 37 degrees C compared with growth at 30 degrees C.
      However, increased amounts of HSP 12 were present in yeast after entry into
      stationary phase; this was enhanced by growth in the osmolytes NaCl and mannitol.

PMID- 9617820
TI  - Down-regulation of specific members of the glutamine synthetase gene family in
      alfalfa by antisense RNA technology.
AB  - Glutamine synthetase (GS) catalyzes the ATP-dependent condensation of NH3 with
      glutamate to produce glutamine. In plants GS is an octameric enzyme and is
      located either in the cytoplasm (GS1) or in the chloroplast (GS2). Two distinct
      classes of GS1 genes with unique 3'-untranslated region (3'UTR) have been
      identified in alfalfa. We have demonstrated that the two classes exhibit
      differential expression pattern in the different plant organs suggesting
      different functional roles for the different isozymes. To determine the
      functional significance of the two classes of GS1 genes in alfalfa, we have
      utilized antisense gene constructs aimed specifically at the 3'UTR of the two GS1
      genes and introduced them individually into alfalfa. Our data show that the gene
      constructs are effective in lowering the corresponding transcript level very
      effectively though there were organ-specific differences in the level of
      reduction. No transcript corresponding to the antisense gene construct was
      detected in any of the alfalfa transformants though they accumulated to
      significant levels in transgenic tobacco containing the same construct. This
      suggests that the antisense transcript was not stable in the presence of the
      homologous target sequence. Transgenic alfalfa with up to 80% reduction in the
      transcript level corresponding to each gene class, however, showed no reduction
      in GS activity or GS1 polypeptide level. The results suggest that GS1 mRNA levels
      are not rate-limiting for GS1 polypeptide synthesis and that GS levels are
      controlled both at the transcriptional and translational/post-translational
      level.

PMID- 9617819
TI  - A new class II rice chitinase, Rcht2, whose induction by fungal elicitor is
      abolished by protein phosphatase 1 and 2A inhibitor.
AB  - Among the four classes of chitinase, a class II chitinase had not yet been
      reported for rice. We have isolated and characterized a class II acidic
      chitinase, Rcht2, from rice (Oryza sativa L. cv. Cheongcheongbyeo). The protein
      consists of a single polypeptide chain of 261 amino acid residues and includes a
      putative signal sequence of 29 amino acids at its N-terminus. It has a calculated
      molecular mass of 27,642 Da and an isoelectric point of 5.56. The Rcht2 chitinase
      lacks the cysteine-rich and hinge domains in the N-terminal region of the
      protein, which is the criterion for its classification as a class II chitinase.
      Comparison of the genomic and the cDNA sequence revealed that the coding region
      of Rcht2 consist of three exons of 301, 112, and 370 bp separated by two introns
      of 89 and 984 bp. In suspension-cultured rice cells, the transcript level of
      Rcht2 was dramatically increased by treatment with both glycol chitin and fungal
      elicitor. The application of protein phosphatase 1 and 2A inhibitors, calyculin A
      and okadaic acid, effectively abolished the induction of Rcht2 in response to
      fungal elicitor. In contrast, the activation of Rcht2 transcript was not
      inhibited by both cycloheximide and protein kinase inhibitors. These results
      demonstrate that protein dephosphorylation events play a crucial role in the
      elicitor-mediated induction of Rcht2 in rice cells, while de novo protein
      synthesis is not required for induction.

PMID- 9617821
TI  - Investigation of Agrobacterium-mediated transformation of apple using green
      fluorescent protein: high transient expression and low stable transformation
      suggest that factors other than T-DNA transfer are rate-limiting.
AB  - To investigate early events of Agrobacterium-mediated transformation of apple
      cultivars, a synthetic green fluorescent protein gene (SGFP) was used as a highly
      sensitive, vital reporter gene. Leaf explants from four apple cultivars
      ('Delicious', 'Golden Delicious', 'Royal Gala' and 'Greensleeves') were infected
      with Agrobacterium EHA101 harboring plasmid pDM96.0501. Fluorescence microscopy
      indicated that SGFP expression was first detected 48 h after infection and
      quantitative analysis revealed a high T-DNA transfer rate. Plant cells with
      stably incorporated T-DNA exhibited cell division and developed transgenic calli,
      followed by formation of transgenic shoots at low frequencies. The detection of
      SGFP expression with an epifluorescence stereomicroscope confirmed the
      effectiveness of SGFP as a reporter gene for detection of very early
      transformation events and for screening of putative transformants. The efficiency
      of the transformation and regeneration process decreased ca. 10,000-fold from
      Agrobacterium infection to transgenic shoot regeneration, suggesting that factors
      other than Agrobacterium interaction and T-DNA transfer are rate-limiting steps
      in Agrobacterium-mediated transformation of apple.

PMID- 9617822
TI  - Expressing foreign genes in the pistil: a comparison of S-RNase constructs in
      different Nicotiana backgrounds.
AB  - Transgenic plant experiments have great potential for extending our understanding
      of the role of specific genes in controlling pollination. Often, the intent of
      such experiments is to over-express a gene and test for effects on pollination.
      We have examined the efficiency of six different S-RNase constructs in Nicotiana
      species and hybrids. Each construct contained the coding region, intron, and
      downstream sequences from the Nicotiana alata S(A2)-RNase gene. Among the six
      expression constructs, two utilized the cauliflower mosaic virus (CaMV) 35S
      promoter with duplicated enhancer, and four utilized promoters from genes
      expressed primarily in pistils. The latter included promoters from the tomato
      Chi2;1 and 9612 genes, a promoter from the N. alata S(A2)-RNase gene, and a
      promoter from the Brassica SLG-13 gene. Some or all of the constructs were tested
      in N. tabacum, N. plumbaginifolia, N. plumbaginifolia x SI N. alata S(C10)S(c10)
      hybrids, N. langsdorffii, and N. langsdorffii x SC N. alata hybrids. Stylar
      specific RNase activities and S(A2)-RNase transcript levels were determined in
      transformed plants. Constructs including the tomato Chi2;1 gene promoter or the
      Brassica SLG-13 promoter provided the highest levels of S(A2)-RNase expression.
      Transgene expression patterns were tightly regulated, the highest level of
      expression was observed in post-anthesis styles. Expression levels of the S(A2)
      RNase transgenes was dependent on the genetic background of the host. Higher
      levels of S(A2)-RNase expression were observed in N. plumbaginifolia x SC N.
      alata hybrids than in N. plumbaginifolia.

PMID- 9617823
TI  - A glycine-rich RNA-binding protein gene is differentially expressed during acute
      hypersensitive response following Tobacco Mosaic Virus infection in tobacco.
AB  - During efforts for cloning disease resistance-responsive genes, a cDNA encoding a
      putative Nicotiana glutinosa glycine-rich RNA binding protein (ngRBP) was
      isolated from TMV induced cDNA library. Northern blot hybridization revealed that
      ngRBP gene is negatively regulated during early hours of TMV induced acute
      hypersensitive response (HR). Under greenhouse conditions induced expression of
      ngRBP gene was observed after 24 h following TMV infection. Salicylic acid and
      copper also induced ngRBP mRNA expression. Our findings are suggestive of some
      possible role for ngRBP in plant-pathogen interaction.

PMID- 9617825
TI  - A plant transformation vector with a minimal T-DNA II. Irregular integration
      patterns of the T-DNA in the plant genome.
AB  - A minimal T-DNA binary vector was used for Agrobacterium-mediated transfer of a
      chimeric T4 lysozyme gene located next to the left border, and transgenic potato
      plants which expressed T4 lysozyme protein were identified and further analysed.
      Frequent rearrangements of T4 lysozyme transgenes were detected. A vector
      derivative containing two matrix associated regions (MARs) flanking its multiple
      cloning site was constructed. In transgenic potato plants, reduced variability in
      gene expression due to position effects was detected. When either the donor
      vector contained MAR sequences, or when vector pPCV701 which contains a pBR322
      fragment next to the left border were used, only relatively few rearrangements
      were observed. However, when the T4 lysozyme gene was driven by a CaMV 35S
      promoter modified by multiplied enhancer region carrying either 2 or 4 elements,
      frequent rearrangements were again obtained.

PMID- 9617824
TI  - Construction and characterization of a phycobiliprotein-less mutant of
      Synechocystis sp. PCC 6803.
AB  - A mutant strain of the cyanobacterium Synechocystis PCC 6803, called PAL, (PC-,
      delta apcAB, delta apcE), lacking phycocyanin, allophycocyanin and the core
      membrane linker (Lcm), was constructed. The strain was characterized by
      absorption and fluorescence spectroscopy. The mutant compensates for the absence
      of the major PS II antenna by increasing its PS II/PS I ratio. It is stable and
      grows well albeit more slowly than wild type.

PMID- 9617826
TI  - Filtration capture and immunoelectrochemical detection for rapid assay of
      Escherichia coli O157:H7.
AB  - A new approach for rapid assay of bacteria in liquid samples is described. Cells
      were labeled by incubation with an enzyme-antibody conjugate and captured by
      filtration of the sample/conjugate mixture through a 0.2 microm filter. The
      enzyme-labeled cells were detected by placing the filter on the surface of an
      electrode, incubating with enzyme substrate, and measuring the current produced
      by oxidation of the electroactive enzyme product. Assay time was 25 min and a
      detection limit of approximately 5000 cells/ml was obtained for E. coli O157:H7.
      Background current due to non-specific binding of conjugate to the filter was the
      primary factor controlling the detection limit, and fewer than 50 cells could be
      detected when very small sample volumes (10 microl) were used to minimize
      background current.

PMID- 9617827
TI  - Detection of thioredoxin in human serum and biological samples using a sensitive
      sandwich ELISA with digoxigenin-labeled antibody.
AB  - Thioredoxin is a low molecular weight, redox active protein important in cellular
      proliferation, signal transduction and antioxidant function. Thioredoxin is
      secreted by normal as well as neoplastic cells and is potentially involved in
      paracrine cell communication as suggested by its co-cytokine activity. Thus, the
      thioredoxin level in biological fluids, cells and tissue homogenates could be an
      important indicator of physiological or pathophysiological conditions. Hence, an
      accurate and sensitive measurement is of paramount importance in studies
      involving thioredoxin. We present here an ultrasensitive enzyme linked immuno
      absorbent assay (ELISA) for human thioredoxin using digoxigenin-labelled goat
      polyclonal anti-human thioredoxin. The assay could detect a minimum level of 15
      pg/ml thioredoxin in human serum, cell culture media, and in cell and tissue
      samples. The assay was optimized for concentration of both antibodies, blocking
      agent, plates, incubation time and reaction volumes. Excellent linearity and
      reproducibility were obtained. The assay was applied to different baboon tissues
      and human serum samples. The intrassay coefficient of variation (CV) was between
      6.0 to 14 and the interassay CV was from 1.6 to 11.1. Excellent parallelism of
      standards with serum samples, tissue homogenates or cell lysates was obtained.
      More than 90% recovery of human thioredoxin was observed in 10% human serum. The
      assay is easy to use, rapid, reproducible, but above all it is a quantitative,
      specific and sensitive way to measure thioredoxin in a variety of biological
      specimens.

PMID- 9617828
TI  - Quantitative studies of heteropolymer-mediated binding of inactivated Marburg
      virus to the complement receptor on primate erythrocytes.
AB  - Previous in vitro and in vivo experiments in our laboratory have demonstrated
      that cross-linked bispecific monoclonal antibody (mAb) complexes (Heteropolymers,
      HP) facilitate binding of prototype pathogens to primate erythrocytes (E) via the
      E complement receptor, CR1. These E-bound immune complexes are safely and rapidly
      cleared from the bloodstream. In order to generate a robust bispecific system for
      HP-mediated clearance of real pathogens such as Filoviruses, we have developed
      the necessary methodologies and reagents using both inactivated Marburg virus
      (iMV) and a recombinant form of its surface envelope glycoprotein (rGP). We
      identified mAbs which bind rGP in solution phase immunoprecipitation experiments.
      HP were prepared by chemically cross-linking an anti-CR1 mAb with several of
      these anti-Marburg virus mAbs and used to facilitate binding of iMV and rGP to
      monkey and human E. These HP mediate specific and quantitative binding (> or =
      90%) of both antigens to monkey and human E. Binding was also demonstrable in an
      indirect RIA. E with bound Marburg virus were probed with 125I labeled mAbs to
      the Marburg surface glycoprotein and more than 100 mAbs are bound per E. It
      should be possible to adapt this general approach to other pathogens, and
      experiments underway should lead to an in vivo test of HP-mediated clearance of
      Marburg virus.

PMID- 9617829
TI  - Optimisation of a heterogeneous non-competitive flow immunoassay comparing
      fluorescein, peroxidase and alkaline phosphatase as labels.
AB  - Off- and on-line strategies for a non-competitive heterogeneous flow immunoassay
      were developed comparing three different labels. The samples, containing the
      model compounds digoxin or digoxigenin, were either pre-incubated off-line or on
      line in a mixing coil with excess of labelled anti-digoxigenin Fab-fragments. The
      excess of Fab-fragments was then separated from the digoxin bound Fab-fragments
      by passing the sample through a column with immobilised digoxin. The off-line
      immunochemical detection system is suitable for sensitive high through-put
      screening of the analytes, whereas the on-line system is more suitable for
      coupling as a post-column detection unit to liquid chromatography. The digoxin
      and digoxigenin content in the sample were quantified using fluorescein (F) and
      enzyme (peroxidase (POD), alkaline phosphatase (AP)) labelled Fab-fragments. The
      fluorescein label was directly measured with the fluorescence detector, whereas a
      fluorescent enzyme product was measured in the two enzyme based systems, using 3
      (p-hydroxyphenyl)-propionic acid (HPPA) and hydrogen peroxide for POD and, and 4
      methylumbelliferyl phosphate (4-MUP) for AP. The highest sensitivity and lowest
      limit of detection (LOD) was obtained with the Fab-POD system with LODs for
      digoxin and digoxigenin in the off- and on-line configurations of 0.025 and 0.01
      nM, respectively. The sample through-put for the off- and on-line systems were 43
      and 32 samples per hour, respectively.

PMID- 9617830
TI  - Improved ELISA proliferation assay (EPA) for the detection of in vitro cell
      proliferation by a new Ki-67-antigen directed monoclonal antibody (Ki-S3).
AB  - We describe a simplified and improved proliferation assay based on a conventional
      ELISA system for the in vitro measurement of cellular proliferation (ELISA
      proliferation assay = EPA). The assay is based on a new monoclonal antibody (Ki
      S3) to the proliferation-specific Ki-67-antigen and is carried out in 96-well
      microtiter plates using conventional immunoenzymatic methods. Ki-S3 is an
      immunoprecipitating monoclonal mouse IgG1 antibody, which recognizes a formalin
      resistant epitope of the Ki-67 antigen. It can be used to measure proliferating
      cells in the cell cycle phases G1, S, G2 and M. In phytohemagglutinin (PHA)
      stimulated peripheral blood mononuclear cells (PBMC) the absorbance values
      obtained with the EPA show a statistically significant correlation to the number
      of Ki-S3 positive cells in simultaneously immunostained cytospin slides (r =
      0.88). A direct comparison with [3H]thymidine labeling reveals the test to be an
      equally sensitive method for monitoring cellular proliferation (r = 0.91). This
      assay is an improved ELISA proliferation assay, which is easy to perform, does
      not require time-consuming pretreatments and avoids the hazards of radioactive
      isotopes.

PMID- 9617831
TI  - Flow cytometric quantitation of yeast a novel technique for use in animal model
      work and in vitro immunologic assays.
AB  - Animal models of fungal and other infectious diseases often require that the
      number of organisms in tissue be quantified, traditionally by grinding organs,
      plating them on agar and counting colony forming units (CFU). This method is
      labor intensive, slow as some fungi require two weeks of culture and limited in
      reliability by poor plating efficiency. To circumvent these problems, we
      developed a flow cytometric method to quantify yeast. In vitro cultured
      Blastomyces dermatitidis, Cryptococcus neoformans, Candida albicans and
      Histoplasma capsulatum yeast were labelled with specific monoclonal or polyclonal
      antibodies to stain surface determinants or with Calcofluor to stain cell-wall
      chitin. A defined number of fluorescently labelled beads were added prior to
      acquisition by flow cytometry as a reference standard for quantitation. Beads
      were readily distinguished from yeast by forward scatter, side scatter and
      intensity of fluorescence. Cultured yeast were enumerated by both standard CFU
      determination and flow cytometry in a range of 10(2) to 10(7) cells. Only flow
      cytometry enabled discrimination of live and dead yeast by using appropriate
      fluorescent dyes. The flow cytometric method was applied to murine models of
      histoplasmosis and blastomycosis to quantify the burden of fungi in the lungs of
      infected mice. Labelling yeast with Calcofluor alone resulted in unacceptably
      high levels of nonspecific binding to mouse cell debris. In contrast, labelling
      H. capsulatum with a rabbit polyclonal antiserum and B. dermatitidis with a
      monoclonal antibody to the surface protein WI-1 permitted accurate quantitation.
      We conclude that this flow cytometry technique is rapid, efficient and reliable
      for quantifying the burden of infection in animal models of fungal disease. The
      technique also should lend itself to performing cytotoxicity assays that require
      discrimination of live and dead fungi, or phagocytosis assays that require
      discrimination of intracellular and extracellular organisms.

PMID- 9617832
TI  - A flash-type bioluminescent immunoassay that is more sensitive than radioimaging:
      quantitative detection of cytokine cDNA in activated and resting human cells.
AB  - Because of its high sensitivity, bioluminescence (BL) is an excellent alternative
      to radioactive quantitation of cytokine RT-PCR-derived products. BL also allows
      detection of amplicons at cycle numbers not normally detectable using
      radioactivity. No direct comparisons between these two methods have been made. In
      this study, the sensitivities of BL using recombinant aequorin, a flash-type
      luminescent tag capable of detecting signal to attomolar (10(-18) M) levels and
      radio imaging (RI) were directly compared. In addition, the application of BL for
      detecting cytokine message from biologic samples was examined. BL was 30- to 60
      fold more sensitive than RI in detecting human IL-2 and CD3delta amplicons. This
      difference was particularly found during low cycle PCR, but was less at higher
      cycle numbers. The ability of BL to detect differences in cytokine message in
      stimulated and unstimulated human peripheral blood mononuclear cells was also
      evaluated. Using linear regression analysis, we observed up to 5,000-fold
      increases in RT-PCR amplified-mRNA in stimulated cells for IL-1alpha, IL-1beta,
      IL-2, IL-4, IL-5, IL-6, IL-10 and GM-CSF compared to unstimulated cells. Changes
      in CD3delta, TNF alpha or IL-12 were not observed or quantitated. We present a
      novel aequorin-based application of bioluminescent technology to directly
      quantitate RT-PCR amplicons and to investigate the induction of human cytokine
      expression. Significant advantages of this sensitive bioluminescent method
      compared with radioactive methods are its abilities to quantitate amplicons in a
      PCR cycle range where linear detection is most robust and to analyze products in
      an automated, open-architecture microtiter plate format.

PMID- 9617833
TI  - A novel method for DEAE-dextran mediated transfection of adherent primary
      cultured human macrophages.
AB  - Primary cultured human macrophages are difficult to transfect. We have developed
      a DEAE-dextran DNA transfection method that mediates the reproducible
      transfection of primary cultured adherent human macrophages. Three factors
      essential for successful transfection were identified: DEAE-dextran
      concentration, the quantity of DNA per transfection and the incubation time of
      the macrophages with the transfection medium. Maximum levels of luciferase
      expression were attained within 24 h and maintained for at least 56 h after
      transfection. While serum in the transfection medium attenuated transfection, the
      treatment of the macrophages with chloroquine, DMSO, or glycerol did not enhance
      transfection within this system. A CMV enhancer/promoter mediated substantially
      greater luciferase expression in the macrophages than either HIV or RSV LTRs.
      DEAE-dextran facilitated superior transfection compared to either cationic
      liposome and calcium phosphate methods, and was more practical compared to
      electroporation for multiple transfections. This transfection protocol provides a
      simple, inexpensive, reproducible method for the evaluation of gene expression in
      primary cultured adherent human macrophages.

PMID- 9617834
TI  - Particle enhanced immunoassays stabilized by hydration forces: a comparative
      study between IgG and F(ab)2 immunoreactivity.
AB  - In previous publications we have discussed the stabilization mechanism of
      hydration forces as applied to the development of latex agglutination tests. We
      describe here how we have obtained stable and reactive IgG-latex conjugates in a
      high-ionic-strength reaction buffer. To this end we have made agglutination tests
      with polystyrene beads sensitized with IgG, measuring the immunoaggregation
      reaction with human C-reactive protein in a stopped-flow nephelometer. The
      results are compared to those obtained with a F(ab')2-latex conjugate with
      similar antibody molecule coverage. Adsorption isotherms of F(ab')2 and IgG on
      latex at pH 7.2 were obtained to study the affinity of these antibodies for the
      surface. The results of the electrokinetic characterization of the antibody-latex
      conjugates agree satisfactorily with those obtained from stability studies. This
      research throws light upon the use of hydration forces as a new approach to
      stabilizing immunoassay reagents that are colloidally unstable in physiological
      reaction buffers.

PMID- 9617835
TI  - An automated method for determination of antibody affinity distribution functions
      with nanogram quantities.
AB  - We have developed a method to determine the binding affinity distribution
      functions (the probability density function for affinity constants will be
      referred to as affinity distribution throughout the text) for human serum antigen
      specific IgE for their respective allergens. This fully automated method, based
      on the Access technology of Sanofi Diagnostics Pasteur, is a highly sensitive two
      step sandwich immunoassay requiring only nanogram quantities of antibodies.
      Allergen-antibody binding isotherms can be determined covering a range of 5
      magnitudes of ligand (allergen) concentration. An affinity distribution function,
      describing the polyclonal nature of the antibody response, can be calculated from
      the binding isotherm. The validity of the method is assessed using mAbs against
      the purified allergen Der p 1. The resolving power and sensitivity of the method
      are demonstrated using selected sera from donors with high and low levels of
      specific IgE for these allergens. We are able to show that heterogeneous IgE
      populations can be determined using 100 microl of sera containing 150 pg of
      specific IgE per ml. Overall, the range of affinities that can be determined by
      this method is 1 x 10(6)-1 x 10(11) M(-1).

PMID- 9617836
TI  - Capture-ELISA based on recombinant PR3 is sensitive for PR3-ANCA testing and
      allows detection of PR3 and PR3-ANCA/PR3 immunecomplexes.
AB  - Proteinase 3 (PR3), a constituent of azurophil granules of neutrophils
      (polymorphonuclear cells, PMNs), is the target antigen for most anti-neutrophil
      cytoplasmic antibodies (c-ANCA) in Wegener's granulomatosis (WG). We have
      recently developed an expression system for recombinant PR3 (rPR3) that is
      recognized by c-ANCA. Here, we report on the development and characterization of
      two monoclonal antibodies (moABs) and a rabbit polyclonal antiserum generated
      against this rPR3. Epitope competition analysis indicates that the moABs MCPR3-1
      and MCPR3-2 recognize overlapping epitopes on the PR3 molecule that are distinct
      from the ones recognized by moABs 4A5 and 6A6 developed by others. Since MCPR3-2
      does not appear to compete for epitopes recognized by a sizable proportion of PR3
      ANCA, we used it to develop a sensitive capture enzyme linked immunosorbent assay
      (ELISA) for clinical PR3-ANCA testing. Both purified PMN PR3 and crude human mast
      cell line (HMC-1)/PR3-S176A cell lysates were used as sources of PR3 target
      antigen in this assay with equal analytical sensitivity and specificity. Of 109
      patients with ANCA-associated disease, 91 (83.5%) and 90 (82.6%) were PR3-ANCA
      positive by capture ELISA when PMN-PR3 and HMC-1/PR3-S176A cell lysates were used
      as antigen, respectively. When HMC-1/PR3 and HMC-1/PR3-S176A cells were used as
      indirect immunofluorescence (IIF) substrate, 88 (80.7%) and 92 (84.4%) were PR3
      ANCA positive, respectively. These differences were not statistically
      significant. Only 1 of 151 controls without defined ANCA-associated disease
      tested positive by capture ELISA with either target antigen (both negative by PR3
      ANCA specific IIF). The capture ELISA can also be used to detect of PR3-ANCA
      immunecomplexes and, in combination with the rabbit antiserum, for the
      quantitative measurement of PR3 in biological fluids.

PMID- 9617837
TI  - Application of an ELISA-elution assay as a screening tool for dissociation of
      yolk antibody-antigen complexes.
AB  - A modified enzyme-linked immunosorbent assay termed ELISA-elution assay was used
      as a screening tool to compare the efficiency of eluents for the dissociation of
      hen yolk immunoglobulin IgY bovine IgG complexes. The potential denaturing
      effects of the eluents were also monitored. Different buffers (pH 2.3-7.5),
      containing various types and concentrations of salts (NaCl, (NH4)2SO4 and MgCl2)
      as well as polyols (ethylene glycol (EG) and glycerol) were compared to the
      commonly reported glycine x HCl (pH 2.8) buffer and to a commercially available
      eluent, Actisep. Acidic pH buffers, Actisep and MgCl2 (3.5 M with EG or 4 M
      without EG) all successfully dissociated IgY from immobilized IgG. However, some
      denaturation was apparent using MgCl, and, to a lesser extent, Actisep.
      Furthermore, these same eluents demonstrated a diminished ability for liberating
      IgG from immobilized IgY(IgG). Information on eluent efficacy obtained by the
      ELISA-elution assays was applied to selectively isolate lower affinity antibodies
      for immunoaffinity column chromatography.

PMID- 9617838
TI  - Novel method for in vitro depletion of T cells by monoclonal antibody-targeted
      photosensitization.
AB  - An immunotargeting method (called photo-immunotargeting) has been developed for
      selective in vitro cell destruction. The procedure combines the photosensitizing
      (toxic) effect of light-induced dye-molecules, e.g., hematoporphyrin (HP) and the
      selective binding ability of monoclonal antibodies (mAb) to cell surface
      molecules. The photosensitizer HP molecules were covalently attached to
      monoclonal antibodies (a-Thy-1) recognizing an antigen on the surface of T
      lymphocytes, and used for T cell destruction. To increase the selectivity of the
      conventional targeting methods, a physical activation step (local light
      irradiation) as a second degree of specificity was employed. The HP in conjugated
      form was sufficient to induce T cell (thymocytes, EL-4 cell line) death after
      irradiation at 400 nm, at tenfold lower concentration compared to the
      photosensitizing effect of unbound HP. The selective killing of T lymphocytes
      (bearing the Thy-1 antigen) in a mixed cell population was demonstrated after a
      treatment with the phototoxic conjugate and light irradiation. This method can be
      useful for selective destruction of one population (target cell) in an in vitro
      heterogeneous cell mixture, e.g., in bone marrow transplants for T cell depletion
      to avoid graft vs. host reaction.

PMID- 9617839
TI  - Development of a novel in vitro co-culture system for studying host response to
      native bacterial antigens.
AB  - We have developed a novel co-culture system in which murine splenocytes are
      cultured with live bacteria in the presence of a bacteriostatic antibiotic.
      Superantigens, like staphylococcal enterotoxin B (SEB) are important factors in
      bacterial pathogenicity. Research has shown that superantigens affect numerous
      immune cell types, either directly or indirectly, yet their involvement in
      pathogenic mechanisms remains poorly defined. In these studies, we utilize the co
      culture system to study how superantigen pretreatment affects interferon-gamma
      (IFN-gamma) production by splenocytes co-cultured with gram-positive bacteria.
      Streptococcus mutans, S. sanguis and Bacillus subtilis were tested for
      susceptibility to a panel of antibiotics. Spectinomycin was found to maintain a
      bacteriostatic state of approximately 10(5) bacteria ml(-1) at optimal
      concentrations for each bacterial strain. Co-culturing splenocytes with bacteria
      did not affect splenocyte viability and cultured splenocytes responded to
      mitogenic stimulation as expected. Two days after SEB pretreatment, isolated
      splenocytes cultured with either Streptococcus species produced 10-15 times more
      IFN-gamma than splenocytes from sham-injected controls; however, no differences
      in CD4+ or CD8+ T cell populations appeared in cultures with or without bacteria.
      Splenocytes isolated four days after SEB treatment did not produce significant
      amounts of IFN-gamma in co-culture. Co-cultures containing live bacteria produced
      four times more IFN-gamma than cultures containing heat-killed bacteria.
      Splenocytes depleted of natural killer (NK) cells prior to SEB treatment produced
      25% less IFN-gamma after 20 h co-culturing with S. mutans. T lymphocytes were
      identified to be the major producer of IFN-gamma at this time point by
      intracellular cytokine staining. Apparently SEB exposure primes a response to
      live bacteria and the response is evident two days after initial exposure. The in
      vitro co-culture system allows us to observe host responses to bacteria in the
      context of the multicellular interdependent immune response. With this assay we
      can more closely 'mimic' in vivo events, particularly immune cell interactions in
      microfloral environments, to study how the pathogenic effects of superantigens
      alter this response.

PMID- 9617840
TI  - Development of an ultrasensitive in vitro assay to monitor growth of primary cell
      cultures with reduced mitotic activity.
AB  - Primary cell cultures, such as isolated epithelial cells, neuronal cells, or
      hepatocytes are characterized by a very low mitotic activity. Monitoring of small
      changes in cell numbers requires staining with a DNA-specific dye with an
      extremely high sensitivity and a low inter- and intraassay variability. For this
      purpose, an ultrasensitive in vitro assay has been developed based on the
      fluorescent nucleic acid stain PicoGreen. PicoGreen has been shown to detect as
      little as 0.5 ng pure DNA or 10(2) cells (interassay SD < 10%, intraassay SD <
      5%). This is far above the limit of sensitivity of conventional fluorochromes,
      such as Hoechst 33342 or propidium iodide. To obtain optimum efficacy of
      PicoGreen, cells were digested with papain for 20 h at 60 degrees C prior to
      staining. Under these conditions, the slope factor was calculated to be 0.105
      relative fluorescence units (RFU)/cell, which is far superior to the slope factor
      of Hoechst 33342 (0.0137 RFU/cell) or propidium iodide (0.0077 RFU/cell).
      Analysis of the blank values revealed a very low autofluorescence of PicoGreen,
      which is only 1/50th of the autofluorescence of Hoechst 33342 and 1/5th of the
      autofluorescence of propidium iodide. Additional coating of the culture plates
      with extracellular matrix proteins to prevent cellular dedifferentiation did not
      influence the high sensitivity of PicoGreen. In conclusion, the PicoGreen-assay
      seems to be the method of choice when the growth capacity of primary cell
      cultures needs to be analyzed with high accuracy.

PMID- 9617841
TI  - An enzyme based assay for the measurement of complement mediated binding of
      immune complexes to red blood cells.
AB  - A new in vitro method is presented for measuring directly the ability of sera to
      induce binding of immune complexes (ICs) to erythrocytes (ICRB assay). The assay
      measures the binding of alkaline phosphatase (AP)-anti-alkaline phosphatase (anti
      AP) complexes formed in the presence of the test sera to the complement receptor
      1 (CR1) on normal human red blood cells (RBCs). By using a standard serum source,
      the assay can also be used to measure the IC binding ability of RBCs from
      different donors. As compared to the traditional CH50 method, the ICRB assay
      generally showed more pronounced abnormality in 10 individuals tested, of whom 5
      had primary deficiency of classical pathway components. Seven out of ten
      individuals had systemic lupus erythematosus (SLE) and 2/10 had other rheumatic
      diseases without primary complement deficiency. The ICRB measured in samples from
      9 other patients with SLE was significantly decreased when compared to values
      from 80 normal individuals. ICRB in serum samples from a C2 deficient SLE patient
      collected during plasma infusion treatment reflected closely the rising amount of
      C2 in the serum. Using RBCs from different donors ICRB activity correlated well
      with the numbers of CR1 as measured by a flow cytometric assay (FCA). These
      methods should be valuable for measuring the overall IC clearance capacity of the
      blood and have the advantage that the use of radioactive isotopes is avoided.

PMID- 9617842
TI  - A novel ELISA for the evaluation of the classical pathway of complement.
AB  - Assessment of the overall function of the classical pathway of complement is
      traditionally performed by the hemolytic titration assay CH50. In the present
      study, we established a novel method for the quantitation of complement activity
      by measuring the deposition of C1q, C4, C3 and C9 on solid-phase IgM by an enzyme
      linked immunosorbent assay (ELISA). Using the CH50 method as the reference, C9
      deposition values displayed a sensitivity of 96.3% and a specificity of 99.4% in
      sera from patients with a variety of diseases. For C3, the sensitivity was 91.3%
      and the specificity 100%, for C4, the values were 95% and 100%, and for C1q the
      corresponding values were 52.9% and 98.9%. A close correlation was found between
      CH50 values below 30 U/ml and the deposition of C9 (r = 0.92), C3 (r = 0.91) and
      C4 (r = 0.92). In two patients with postinfectious glomerulonephritis normal C4
      and C1q deposition was accompanied by decreased C3 and C9 deposition reflecting
      complement activation predominantly through the alternative pathway. In contrast,
      in two patients with complete C2 deficiency the deposition of C3 and C9 was
      undetectable together with normal C4 deposition values. Furthermore, in two
      patients with hereditary C1-inhibitor deficiency distinctly increased C1q
      deposition was accompanied by decreased C4 deposition values. In conclusion, the
      determination of complement deposition by ELISA represents a novel, quantitative
      method for the evaluation of complement activity. The measurement of C9
      deposition alone or in combination with further complement proteins makes this
      ELISA a valuable tool for assessing the degree and level of complement
      consumption as well as localizing the missing protein in the case of complement
      deficiencies.

PMID- 9617843
TI  - Immunopurification of human beta2-glycorprotein I with a monoclonal antibody
      selected for its binding kinetics using a surface plasmon resonance biosensor.
AB  - The beta2-glycoprotein I (beta2GPI)-binding properties of five murine monoclonal
      antibodies immobilized as capture antibodies were studied using surface plasmon
      resonance detection. The monoclonal antibody with the fastest dissociation
      kinetics (6F3) was selected for the development of an immunoaffinity
      chromatography procedure, assuming that its behaviour would be similar in both
      systems since the covalent coupling chemistries involved amino groups in both
      cases. Under our experimental conditions of a fast one-step procedure, beta2GPI
      was purified to homogeneity from human plasma with a yield of about 50%. Beta2GPI
      was eluted under fairly mild conditions, either at low pH or at high pH. The
      immunoadsorbent was used five times without any apparent loss of binding
      capacity. The immunopurified protein showed similar binding to cardiolipin-coated
      polystyrene wells as beta2GPI purified by conventional methods. However,
      differences in the pattern of immunoreactivity in relation to the purification
      procedure were observed by surface plasmon resonance using the monoclonal
      antibody with the highest association kinetics (9G1) immobilized on the sensor
      surface.

PMID- 9617844
TI  - Laboratory protocols for the quantitation of cytokines by bioassay using cytokine
      responsive cell lines.
AB  - Cytokines have been shown to be involved in many physiological processes,
      including the maintenance and control of a competent haematopoietic/immune
      system. Abnormal cytokine secretion or synthesis can cause a wide range of
      pathological disorders. Cytokines have also been shown to have therapeutic
      potential in many diseases. In order for the role of cytokines to be evaluated in
      normal and pathogenic processes, it is vital that appropriate assay systems are
      used to measure their levels in different biological fluids. Whilst immunoassays
      maybe a more convenient method for quantitating cytokines, they only measure
      immunologically reactive material. They may or may not detect biologically
      inactive material, such as cytokines bound to soluble receptors or degraded
      cytokine molecules. Bioassays, however, detect biologically active cytokines and
      can be as accurate and precise as immunoassays. The purpose of these protocols is
      to provide practical stepwise methods for the bioassay of cytokines using
      cytokine responsive cell lines. They include tables of the most useful currently
      available cell lines for the detection of cytokines and how to maintain them. In
      addition, these protocols provide all the materials and methods in a logical step
      by-step procedure to carry out bioassays. Information is provided on possible
      pitfalls and general problems associated with bioassays and how to overcome them.
      These protocols should be valuable to scientists new to the cytokine field as
      well as experienced scientists who require a consensus methodology and access to
      information on cell lines useful for cytokine bioassays.

PMID- 9617845
TI  - Alzheimer's disease: making progress through a multidisciplinary approach.
      Introduction.

PMID- 9617846
TI  - The initial recognition and diagnosis of dementia.
AB  - Dementia is characterized by a decline in cognition, behavioral disturbances, and
      interference with daily functioning and independence. Diagnosis is sometimes
      delayed as patients or family members often misattribute obvious manifestations
      of cognitive decline to normal aging rather than to the onset of a degenerative
      disease. Many physicians do not perform mental status examinations or do not use
      them effectively to detect early symptoms. Clinical markers are available to
      decrease the difficulty in distinguishing dementia from depression and
      confusional states such as delirium. Alzheimer's disease (AD) is the most common
      form of dementia; others include rapidly progressive dementias, dementias
      associated with strokes and Parkinson's disease, and frontotemporal dementias.
      Often, AD coexists with other forms of dementia. Sensitivity to early warning
      signs, interviews with family members, and mental status examinations are
      essential to early detection of AD, and will prove useful to primary-care
      physicians who care for older patients.

PMID- 9617847
TI  - A multidisciplinary approach to Alzheimer's disease: who should be members of the
      team?
AB  - The treatment goal for persons with Alzheimer's disease (AD) is to maintain the
      highest level of function possible and to minimize behavioral disturbances. Since
      multiple factors have an impact on function, a multidisciplinary approach to
      treatment and care is most effective. Whereas the primary-care physician can
      diagnose AD in most patients, data collection and routine examinations can be
      conducted by a nurse practitioner/clinical nurse specialist, and nonprofessional
      staff can often do mental status testing. Nutritionists, pharmacists,
      geropsychiatrists, home-healthcare case managers, elder-law attorneys, support
      services, and caregivers all fill important roles as members of the "AD team."
      With two AD drugs currently available and several impending new introductions,
      pharmacotherapy is becoming an increasingly more critical treatment option.

PMID- 9617848
TI  - Social issues of the Alzheimer's patient and family.
AB  - Families caring for a person with Alzheimer's disease (AD) soon discover that it
      is unlike any other illness. Coping with a degenerative brain disease is much
      different than dealing with a physical disability. AD is more disruptive to, and
      has greater impact on, the family than other chronic diseases. AD caregiving
      carries with it a high financial, social, and emotional price. Families must work
      toward effectively coping with the disease, decreasing the harmful effects on the
      family, and keeping family conflicts to a minimum. Support groups can provide
      families with much-needed information on the disease, emotional and practical
      support, and an expressive or advocacy outlet. Formal services can help relieve
      some of the burden of caring for an AD patient. Family members must remember that
      there is no "right" way to care for a person with AD, and each family must
      determine, with the help of the appropriate professionals and services, how to
      best meet its own needs. Given the burdens of care, however, even small
      interventions may translate into improvements in the quality of life or
      confidence of the caregiver.

PMID- 9617849
TI  - Elder law and Alzheimer's disease.
AB  - The elder-law practice focuses on the particular needs of older individuals and
      their families. Thus, elder law is truly "family" law because the needs of older
      clients are inextricably interwoven with the needs of their families. This is
      particularly true for the client who is chronically ill or has some form of
      dementia, such as Alzheimer's disease. Elder-law attorneys may now be certified
      to identify to the public those lawyers who demonstrate enhanced knowledge,
      skills, experience, and proficiency in elder law. Elder law draws from many
      substantive areas, such as trust, real property, agency, health care, tax,
      guardianship, will and probate, Social Security, Medicare, and Medicaid law.
      Together, the client and family are educated on legal options and are assisted in
      making decisions, formalized through legal documentation. The emphasis is on
      advance planning. Among legal practitioners, elder-law attorneys understand most
      clearly that the client's needs must be understood in the context of cultural and
      family dynamics, and addressed through a team approach involving other
      professions.

PMID- 9617850
TI  - An overview of Alzheimer's disease research.

PMID- 9617851
TI  - Treatment of Alzheimer's disease: current approaches and promising developments.
AB  - Alzheimer's disease (AD) is characterized by a gradual decline in 3 domains:
      cognition, behavior, and function. Ideally, an effective treatment would target
      all 3 types of impairment. However, available treatments for AD diminish only
      certain symptoms and cannot halt the dementing process. Most pharmacologic agents
      currently available or in development target a specific symptom cluster (e.g.,
      cognitive loss), and are based on the known neurobiology of the disease (e.g.,
      neurotransmitter deficit) or hypothesized antidementia approaches (e.g., anti
      inflammation, antioxidation). Two currently available cholinesterase inhibitors
      improve memory and other aspects of cognition during short-term treatment.
      Additional cholinergic agents will soon become available. Other promising agents
      under study for cognitive enhancement or protection include vitamin E,
      selegiline, estrogen, and nonsteroidal anti-inflammatory drugs. As scientists
      uncover the basic pathogenetic mechanisms of AD, additional treatments will
      likely emerge. Therapies for behaviors associated with dementia (e.g.,
      depression, agitation, anxiety) are sometimes effective. Choices of specific
      medications, including antidepressants, antipsychotics, and anxiolytics, depend
      on specific side-effect profiles. Psychotherapies aimed at enhancing cognition
      are ineffective for dementia but nonpharmacologic interventions may minimize
      depression and agitation and may improve quality of life.

PMID- 9617852
TI  - Cytokines and immunomodulatory therapy in inflammatory bowel disease.

PMID- 9617853
TI  - The etiology of isolated thyroid stimulating hormone deficiency.

PMID- 9617854
TI  - Molecular basis of lymphomagenesis in B-cell maturation.

PMID- 9617855
TI  - Erythropoietin therapy for aplastic anemia.

PMID- 9617856
TI  - Obliterative small airway diseases in rheumatoid arthritis.

PMID- 9617857
TI  - Autologous blood transfusion.
AB  - Autologous blood transfusion is an endorsed blood conservation strategy that has
      become widely practiced in elective surgical procedures. We review ten years'
      experience in this arena, along with emerging strategies designed to continue to
      minimize allogeneic blood exposure but reduce the costs associated with
      autologous blood procurement. We conclude that point-of-care autologous blood
      procurement (acute normovolemic hemodilution and intraoperative autologous blood
      salvage) can replace the predonation of autologous blood in surgical patients
      when transfusion medicine specialists, anesthesiologists, and surgeons develop a
      prospective, comprehensive approach to blood conservation.

PMID- 9617858
TI  - Incidence and characteristics of thyroid dysfunction following interferon therapy
      in patients with chronic hepatitis C.
AB  - Thyroid functions were analyzed before, during and after interferon (IFN) therapy
      in patients with chronic hepatitis C. According to the results of routine thyroid
      function tests and measurements of the levels of anti-thyroid autoantibody prior
      to the therapy, patients were divided into 2 groups; Group A (19 patients) had at
      least one abnormal finding related to the thyroid, and Group B (40 patients) did
      not show any abnormality. Five patients (26%) in Group A and 4 (10%) in Group B
      showed thyroid dysfunctions which were very clearly reflected by thyrotropin
      (TSH) measurements. Interestingly, the time of peak TSH elevation in Group A
      (mean +/- SD, 4.3 +/- 0.8 months) was significantly earlier than that in Group B
      (6.8 +/- 0.8). Most patients in Group B were diagnosed as having destructive
      thyroiditis. These findings may suggest that the pathogenesis of IFN-induced
      thyroid dysfunction consists not only of exacerbation of pre-existing thyroid
      autoimmunity but also of de novo destructive changes even in the intact thyroid
      before IFN therapy.

PMID- 9617859
TI  - Correlations between interleukin-8, and myeloperoxidase or luminol-dependent
      chemiluminescence in inflamed mucosa of ulcerative colitis.
AB  - Interleukin-8 (IL-8) is a peptide which induces not only chemotaxis of
      neutrophils but also the release of reactive oxygen metabolites from the
      neutrophils. There are few reports which clarify the relationships between IL-8
      and mucosal infiltration of neutrophils or reactive oxygen metabolites produced
      by neutrophils in the colonic mucosa of ulcerative colitis (UC). Biopsy specimens
      of colonic mucosa obtained from 26 patients with active UC and 21 patients with
      inactive UC were studied in order to clarify the relationships among the
      inflammation factors in UC. Levels of IL-8 and myeloperoxidase in organ culture
      media of the biopsy specimens from active UC (measured by ELISA and EIA) were
      significantly higher than those from inactive UC and controls. Reactive oxygen
      metabolites of biopsy specimens in active UC (measured by luminol-dependent
      chemiluminescence) were also markedly increased compared to those in inactive UC
      and controls. The levels of IL-8 were closely correlated to luminol-dependent
      chemiluminescence or myeloperoxidase levels. However, the levels of IL-8 and
      myeloperoxidase did not correlate with the grades of activity on colonoendoscopic
      findings. These findings suggest that IL-8 may play a role in the pathophysiology
      of UC but it does not define the endoscopic activity grades of UC.

PMID- 9617860
TI  - Color-coded Doppler imaging of subclavian steal syndrome.
AB  - We examined the usefulness of color-coded Doppler echography for evaluating
      hemodynamics in patients with subclavian steal syndrome. Eighteen patients with
      subclavian steal syndrome, aged 54 to 77 years, were investigated. The diagnosis
      was confirmed by conventional angiography and pulsed-wave Doppler sonography.
      Using color-coded Doppler echography, the common, internal and external carotid
      and vertebral arteries and the subclavian artery on the affected side were
      visualized. In all patients, color-coded images of the antegrade common carotid
      arterial flow and the retrograde vertebral arterial flow on the affected side
      were obtained. Rapid flow through stenotic lesions and reflux from vertebral to
      subclavian arteries at the vertebral arterial ostia were observed. Color-coded
      Doppler echography is superior to duplex echography without the color-coded mode,
      because the flow through the affected vertebral and subclavian arteries can be
      easily traced in detail and the images are persuasive. This method is beneficial
      for diagnosing subclavian steal syndrome.

PMID- 9617861
TI  - Clinical manifestations due to a point mutation of the mitochondrial tRNAleu(UUR)
      gene in five families with diabetes mellitus.
AB  - It has been shown that an adenine (A) to guanine (G) transition at position 3243
      of the mitochondrial transfer RNA(tRNA)leu(UUR) gene is associated with a
      subgroup of diabetes mellitus. Therefore, we screened for this transition in 86
      patients with non-insulin-dependent diabetes mellitus (NIDDM) in which two or
      three generations were affected with diabetes, in 14 patients with insulin
      dependent diabetes mellitus, and in 9 families with diabetes mellitus and/or
      associated disorders suggesting mitochondrial gene abnormalities. We failed to
      identify the mutation in 100 diabetic patients, 86 NIDDM and 14 insulin-dependent
      diabetes mellitus (IDDM). Out of the latter 9 families, we identified an A to G
      transition in 14 individuals in 5 families. Diabetes mellitus was shown to be
      maternally inherited in one family. In 9 of 14 patients with the mutation,
      insulin was required to treat diabetes mellitus, indicating impaired insulin
      secretion. A hyperglycemic clamp test performed in one subject revealed
      significant impairment of insulin secretion, whereas euglycemic clamp test showed
      normal insulin sensitivity in this patient. The heteroplasmy of the mutant
      mitochondrial DNA (mtDNA) in leukocytes does not appear to correlate with the
      severity of diabetes in terms of the insulin therapy required. Body mass index of
      the affected individuals was less than 23.3. In one family, in addition to
      diabetes mellitus and hearing loss, hypoparathyroidism was associated with the
      mutation, suggesting that hypoparathyroidism is caused by the impaired processing
      and/or secretion of proparathyroid hormone due to the mutation. In addition, the
      affected subjects presented with proteinuria at the time of diagnosis of diabetes
      mellitus which appeared not to be related with diabetic nephropathy.

PMID- 9617863
TI  - Arterial and mixed venous oxygen desaturation during incremental exercise in
      patients with chronic pulmonary disease.
AB  - We evaluated arterial and mixed venous oxygen desaturation during symptom-limited
      exercise in patients with chronic pulmonary disease. Patients were divided into
      five groups according to disease: [chronic pulmonary emphysema (CPE), chronic
      bronchitis (CB), pulmonary tuberculosis sequalae (TB-seq), fibrosing lung disease
      (FLD), and pulmonary vascular disease (PVD)]. There were no significant
      difference in the values of arterial (PaO2) and mixed venous (PvO2) oxygen
      tension before and at the end of exercise among the five groups, whereas absolute
      decreases in PvO2 were significantly larger in PVD and FLD. The changes in PvO2
      were similar to the changes in the coefficient of oxygen delivery (COD) which is
      equal to oxygen transport divided by oxygen consumption. These results suggest
      that the relative decrease in oxygen transport during exercise due to the high
      ratio of oxygen extraction by tissues is an important factor to determine
      decreases in PvO2 in pulmonary hypertensive disease and fibrosing lung disease.

PMID- 9617862
TI  - Low density lipoprotein particle size is associated with glycosylated hemoglobin
      levels regardless of plasma lipid levels.
AB  - We evaluated the influence of the levels of glycosylated hemoglobin (HbA1C) and
      fasting plasma glucose on the variation in low density lipoprotein (LDL) peak
      particle size in 210 subjects who were undergoing an annual check-up. Univariate
      analysis showed that LDL particle size was significantly and positively
      correlated with high density lipoprotein (HDL) cholesterol levels, and was
      inversely correlated with the levels of total plasma cholesterol, triglycerides,
      fasting glucose, fasting insulin, HbA1C, and body mass index (BMI). Stepwise
      regression analysis selected four independent contributing variables that could
      affect LDL particle size; triglyceride levels, HDL cholesterol levels, LDL
      cholesterol levels, and HbA1C levels. Similar regression analysis performed for
      men and for normotensive subjects showed that HbA1C levels also independently
      influenced LDL particle size. The results indicate that HbA1C levels have a
      significant effect on LDL particle size. This suggests that small LDL particles
      would be present in subjects with non-insulin-dependent diabetes mellitus
      regardless of plasma lipid concentrations.

PMID- 9617864
TI  - Utility and safety of Hickman catheters for venous access after bone marrow
      transplantation.
AB  - Hickman catheters are useful for vascular access after bone marrow transportation
      because they can handle large volume and allow for easy transfusions and blood
      drawing through wide double lumens making it easier to case for patients under
      sterile conditions in a clean room. However, the safety of Hickman catheters as
      compared to Silastic catheters in marrow transplants has never been discussed. We
      therefore retrospectively reviewed the complications of two catheters in 71
      allogeneic bone marrow transplant recipients between September 1986 and August
      1994. The complication and infection rates of Hickman catheters were 0.21 and
      0.09 per 100 device-life days, and rate of temperature >38 degrees C during
      leukocytopenia (<1,000 white blood cells) was 0.18. These rates were not
      different from those of Silastic catheters suggesting that Hickman catheters are
      safe and acceptable in marrow transplantation. The benefits and drawbacks of
      Hickman catheters relevant to catheter choice were also discussed.

PMID- 9617865
TI  - Multiple pulmonary metastases with cavitation from gallbladder cancer.
AB  - We report a rare case of multiple pulmonary metastases with cavitation from
      gallbladder cancer. A 77-year-old woman was admitted to our hospital complaining
      of productive cough and exertional dyspnea. Chest X-ray film showed multiple
      nodular shadows with some cavitation. Computed tomography showed multiple
      cavities, up to 2 cm in diameter, as well as nodules, in bilateral lung fields.
      Under a survey of primary focus, the ultrasonographic test of the abdomen
      revealed a hypoechoic mass in the hepatic hilum. The patient died of respiratory
      failure. Autopsy findings revealed that that multiple lung tumors had
      metastasized from papillary adenocarcinoma of the gallbladder and that cavitation
      of the lung was formed by bronchioloectasis.

PMID- 9617866
TI  - Islet cell tumor in von Hippel-Lindau disease.
AB  - We describe a 42-year-old man with von Hippel-Lindau disease and islet cell tumor
      of the pancreas. He had retinal and cerebellar hemangioblastomas. His sister had
      pheochromocytoma. A pancreatic tumor was detected by ultrasonography at his
      periodical medical checkup. Contrast enhanced computed tomography and abdominal
      angiography revealed a hypervascular tumor in the pancreatic head. Histological
      examination of the resected tumor revealed characteristics of islet cell tumor of
      the pancreas, which was positive for chromogranin-A, S-100 protein, and
      pancreatic polypeptide, but was negative for insulin, gastrin, glucagon,
      somatostatin, vasoactive intestinal peptide, serotonin, and adrenocorticotropic
      hormone.

PMID- 9617867
TI  - Transient isolated thyrotropin deficiency associated with cavernous sinus
      syndrome.
AB  - The cause and course of isolated thyrotropin (TSH) deficiency are not well
      understood. We report a 65-year-old man with a transient, probable isolated TSH
      deficiency associated with cavernous sinus syndrome secondary to tympanitis. On
      his admission, serum TSH and triiodothyronine levels were very low. No TSH
      response to thyrotropin releasing hormone (TRH) was observed. However, 6 years
      later, TSH response to TRH was restored. The present case showed that
      inflammation in the cavernous sinus could be one of the causes of TSH deficiency.
      Further, it demonstrated that TSH deficiency is not always permanent and the
      reevaluation of pituitary function is necessary.

PMID- 9617868
TI  - Sarcoid reactions scattered in the tumor-bearing lung parenchyma and regional
      lymph nodes associated with pulmonary carcinoid.
AB  - A 77-year-old woman was admitted to our hospital because of a mass lesion in the
      left lung. The tumor was pulmonary carcinoid associated with sarcoid reactions in
      the regional lymph nodes and scattered in the resected lung parenchyma. Pulmonary
      carcinoid with sarcoid reactions is extremely rare. This appears to be the first
      case report in which tumor-related sarcoid reactions were studded within the
      tumor-existing lung parenchyma and confirmed not to be within the uninvolved
      right lung.

PMID- 9617869
TI  - KL-6 as a serologic indicator of Pneumocystis carinii pneumonia in
      immunocompromised hosts.
AB  - KL-6, a serum marker for interstitial pneumonitis, was evaluated in patients with
      Pneumocystis carinii pneumonia (PCP). Patient 1 was a 56-year-old woman with
      rheumatoid arthritis treated with immunosuppressive drugs and corticosteroids.
      Patient 2 was a 59-year-old man with a glioblastoma who received anti-cancer
      drugs and corticosteroids. In both patients, serum KL-6 showed an abnormally high
      level due to the complication of PCP, and it decreased following successful
      treatment. These results indicate that PCP is one of the diseases in which serum
      KL-6 increases.

PMID- 9617870
TI  - Non-Hodgkin's lymphoma involving bilateral breasts.
AB  - We describe here two cases of diffuse large cell type non-Hodgkin's lymphoma
      affecting the bilateral breasts. The contralateral tumor in one case appeared 17
      months after the first mastectomy, whereas the bilateral tumors occurred
      concurrently in the other patient who was pregnant and showed widespread
      dissemination at initial presentation. Lymphoma cells from both cases showed the
      mature B-cell immunophenotype and had rearrangements of the BCL6 gene. Both
      patients developed progressive disease despite chemo-radiotherapy and died of
      leukemic manifestations. There were no apparent pathological features of
      lymphomas of mucosa-associated lymphoid tissue origin.

PMID- 9617871
TI  - Pyoderma gangrenosum following cytosine arabinoside, aclarubicin and granulocyte
      colony-stimulating factor combination therapy in myelodysplastic syndrome.
AB  - Pyoderma gangrenosum (PG) is a neutrophilic dermatosis, which may be associated
      with systemic conditions such as hematologic disorders. We present a patient who
      had been diagnosed as having myelodysplastic syndrome associated with PG at
      onset, in whom a febrile ulcerative skin lesion developed following cytosine
      arabinoside, aclarubicin and granulocyte colony-stimulating factor (G-CSF)
      combination chemotherapy in the course of the disease. Skin biopsy revealed dense
      neutrophilic infiltrate in the dermis with central epidermal ulceration,
      consistent with the diagnosis of PG. Oral prednisolone was effective for the skin
      lesion. In this case, G-CSF application may participate in the recurrence of PG.

PMID- 9617872
TI  - Sustained improvement in anemia with low-dose recombinant human erythropoietin
      therapy in a patient with hypoplastic myelodysplastic syndrome and chromosomal
      abnormalities.
AB  - We present a case report of a 55-year-old male patient with hypoplastic
      myelodysplastic syndrome (MDS, refractory anemia) in which a good response to
      recombinant human erythropoietin (rhEPO) has been maintained for more than 60
      months. There is with no evidence of progression to high risk MDS or acute
      leukemia, although he was predicted to be a low-responder to rhEPO therapy
      because of very high serum EPO levels (5,260 mU/ml), a history of multiple
      transfusions, chromosomal abnormalities (47,XY,+8) and severe thrombocytopenia.
      Since he received rhEPO with no adverse effects, it may be valuable to try rhEPO
      treatment at least one time for low-risk MDS patients, depending on red cell
      transfusion requirements.

PMID- 9617873
TI  - An autopsy case of peripheral neuroepithelioma in posterior mediastinum with p53
      point mutation.
AB  - An 18-year old male was admitted to our hospital complaining of back pain. His
      chest computed tomography showed a tumor in the posterior mediastinum. Open
      biopsy was performed, and a diagnosis of peripheral neuroepithelioma was made. No
      genetic abnormalities were detected in the DNA obtained from the biopsy specimen.
      He received chemotherapy and radiation several times. These treatment regimens
      were effective, but he relapsed 14 months later and died of respiratory failure
      due to tumor growth. Autopsy examination revealed a large tumor which occupied
      almost the entire right thoracic cavity, but there was no evidence of metastasis
      to other organs. Chromosomal translocation t(14;17) (q24;p12.2) and point
      mutation of exon 5 of the p53 gene were detected.

PMID- 9617874
TI  - Rhabdomyolysis and myocardial damage induced by palytoxin, a toxin of blue
      humphead parrotfish.
AB  - A 55-year-old man had rhabdomyolysis and myocardial damage induced by palytoxin.
      Weakness and myalgia of four extremities occurred five hours after eating a fish.
      Rhabdomyolysis developed and the serum creatine phosphokinase (CK) was elevated
      to 40,000 IU/l on the 3rd day. Gastric lavage with activated charcoal and forced
      mannitol-alkaline diuresis therapy were performed. The patient recovered with no
      complication such as renal failure. In this case, palytoxin was suggested to
      induce myocardial damage which was demonstrated by an elevation of the myosin
      light chain level and a change in electrocardiogram.

PMID- 9617875
TI  - The protective effect of a persistent trigeminal artery on brain stem
      infarctions: a follow-up case report.
AB  - A persistent trigeminal artery (PTA) represents an embryonic vascular anastomosis
      connecting the carotid and basilar arterial systems. Little is known about its
      protective role in cases of basilar artery occlusion. We followed up a 63-year
      old man who had suffered a brain stem infarction due to basilar artery stenosis
      and was found to have a PTA. Although a second brain stem infarction due to
      basilar artery occlusion developed, the circulation to the brain stem was well
      maintained via collateral flow from the PTA, and the patient demonstrated good
      recovery. A PTA may function as an anastomosis between the carotid and basilar
      systems, thus preventing a more serious infarction.

PMID- 9617876
TI  - Rheumatoid arthritis associated with diffuse panbronchiolitis.
AB  - Diffuse panbronchiolitis (DPB) is a distinct clinicopathologic entity, which is
      characterized by chronic recurrent sinopulmonary infection and inflammation. We
      describe 3 patients with rheumatoid arthritis (RA) associated with DPB and
      consider that DPB is one of the bronchopulmonary manifestations associated with
      RA.

PMID- 9617877
TI  - Fatal non-bacterial thrombotic endocarditis following viperine bite.
AB  - Non-bacterial thrombotic endocarditis (NBTE) commonly occurs in patients with
      wasting disease (e.g. malignancy) or with valves damaged following trauma due to
      intra-cardiac foreign body, scarring or marked turbulence. Although disseminated
      intravascular coagulation (DIC) is well documented following viperine bite and
      the underlying mechanism of NBTE is thought to be DIC, there is no report of NBTE
      in humans following snake bite. We report a young male who following viperine
      bite developed local swelling, superficial gangrene of tissues at the site of
      bite, and oliguria and died following multiple cerebral infarcts and acute renal
      failure. The post-mortem examination showed NBTE of the aortic valve, multiple
      embolic infarcts of brain, spleen and kidneys, acute tubular necrosis and
      features of DIC in the brain in the form of fibrin thrombi in the capillaries,
      perivascular hemorrhages and necrosis.

PMID- 9617878
TI  - Trp64Arg mutation of beta3-adrenergic receptor and non-insulin dependent diabetes
      mellitus.

PMID- 9617879
TI  - Study of platelet-activating factor acetylhydrolase in the perioperative period
      of patients undergoing cardiac surgery.
AB  - After operations with cardiopulmonary bypass, patients often show early symptoms
      of the systemic inflammatory response syndrome (SIRS). Potential mediators of
      SIRS include the platelet-activating factor (PAF), which has been linked to
      septic shock and multiple organ dysfunction. We studied the effect of cardiac
      surgery on PAF acetylhydrolase, the PAF-degrading plasma enzyme, as well as the
      relationship between the enzyme and the postoperative state of the patients. PAF
      acetylhydrolase activity decreased by 38+/-8% after instituting cardiopulmonary
      bypass because of plasma dilution and returned to near-preoperative levels within
      6 h postsurgery. After that, enzyme levels decreased again, resulting in a 24+/
      12% reduction until at least 3 days postsurgery. Patients in poor postoperative
      condition (Acute Physiology Score >9) had a lower preoperative PAF
      acetylhydrolase activity than did normal patients (12+/-4 vs. 17+/-4 nmol min(-1)
      mL(-1); p < .05). Likewise, patients who developed postoperative SIRS had a lower
      preoperative PAF acetylhydrolase activity than did patients without SIRS (12+/-3
      vs. 17+/-4 nmol min(-1) mL(-1); p < .05). The data suggest that PAF
      acetylhydrolase deficiency is among the factors associated with postoperative
      distress after cardiac surgery.

PMID- 9617880
TI  - Inhibition of nitric oxide synthesis aggravates hepatic oxidative stress and
      enhances superoxide dismutase inactivation in rats subjected to tourniquet shock.
AB  - The role of nitric oxide (NO) on liver oxidative stress and tissue injury in rats
      subjected to tourniquet shock was investigated. This shock model differs from
      others in that injury is a consequence of remote organ damage. Liver oxidative
      stress becomes evident after hind limb reperfusion, as evidenced by the loss of
      total tissue thiols; by increases in tissue oxidized glutathione (GSSG), lipid
      peroxidation (LPO), plasma aminotransferases (alanine aminotransferase (ALT) and
      (aspartate aminotransferase (AST)), and plasma nitrites; and by a 36% loss in
      total superoxide dismutase (SOD) activity. Portal blood flow is reduced by 54.1%
      after 2 h of hind limb reperfusion. Inhibition of NO synthesis with Nomega-nitro
      L-arginine methyl ester or L-arginine methyl ester increased mean arterial blood
      pressure; further reduced portal blood flow; and aggravated liver injury as
      assessed by further loss in total thiols, increased LPO and GSSG content, and
      further increases in plasma ALT and AST. Total plasma nitrites were lower than in
      control animals, and total tissue SOD activity decreased by more than 80%.
      Treatment with the NO donor sodium nitroprusside reverted the decrease in portal
      blood flow and also reverted tissue thiol loss, LPO, and GSSG increases, as well
      as the loss of ALT and AST to plasma and of SOD activity to levels comparable to
      untreated control shock animals. As expected, plasma nitrites were greater than
      in tourniquet control animals. These data support the hypothesis that endogenous
      NO formation protects the rat liver from the consequences of oxidative stress
      elicited by hind limb reperfusion in rats subjected to tourniquet shock.

PMID- 9617881
TI  - Selective inhibition of the activity of inducible nitric oxide synthase prevents
      the circulatory failure, but not the organ injury/dysfunction, caused by
      endotoxin.
AB  - Inhibitors of nitric oxide synthase (NOS) attenuate the circulatory failure
      caused by endotoxin, but the role of NO in the development of multiple organ
      dysfunction and the relative contribution of NO produced by endothelial NOS and
      inducible NOS (iNOS) to organ injury remains unclear. Here we report for the
      first time that 1400W, a novel and highly selective inhibitor of iNOS activity,
      attenuates the delayed hypotension as well as the rise in the plasma levels of
      nitrite/nitrate caused by endotoxin in the rat. Inhibition of iNOS activity with
      1400W administered either before or 2 h after endotoxin injection did not,
      however, attenuate the hepatocellular injury, renal dysfunction, or pancreatic
      injury in this model. Similarly, administration of another selective inhibitor of
      iNOS activity, L-NIL, 2 h after endotoxin injection abolished the rise in
      nitrite/nitrate and attenuated the delayed hypotension caused by endotoxin, but
      failed to ameliorate organ injury. Thus, selective inhibition of iNOS activity
      with 1400W attenuates the circulatory failure induced by endotoxin in the rat,
      but fails to influence the degree of organ injury/dysfunction.

PMID- 9617882
TI  - Peroxynitrate-mediated DNA strand breakage activates poly(ADP-ribose) synthetase
      and causes cellular energy depletion in a nonseptic shock model induced by
      zymosan in the rat.
AB  - The aim of the present study was to investigate the role of poly(ADP-ribose)
      synthetase in a nonseptic shock model, wherein oxyradicals, nitric oxide, and
      peroxynitrite are known to play a crucial role in the inflammatory process. DNA
      single-strand breakage and activation of the nuclear enzyme poly(ADP-ribose)
      synthetase (PARS) triggers an energy-consuming, inefficient repair cycle, which
      contributes to peroxynitrite-induced cellular injury. Here we investigated
      whether peroxynitrite production and PARS activation are involved in cytotoxicity
      in macrophages collected from rats subjected to zymosan-induced shock.
      Macrophages harvested from the peritoneal cavity exhibited a significant
      production of peroxynitrite, as measured by the oxidation of the fluorescent dye
      dihydrorhodamine 123. Furthermore, zymosan-induced shock caused a suppression of
      macrophage mitochondrial respiration, DNA strand breakage, activation of PARS,
      and reduction of NAD+ cellular levels. In vivo treatment with 3-aminobenzamide
      (10 mg/kg intraperitoneally, 1 and 6 h after zymosan injection) or nicotinamide
      (50 mg/kg intraperitoneally, 1 and 6 h after zymosan injection) significantly
      inhibited the decrease in mitochondrial respiration and the activation of PARS,
      and partially restored the cellular level of NAD+. In a separate group of
      experiments, in vivo pretreatment with NG-nitro-L-arginine methyl ester, a
      nonselective inhibitor of nitric oxide synthesis (10 mg/kg intraperitoneally, 15
      min before zymosan administration), reduced peroxynitrite formation and prevented
      the appearance of DNA damage, the decrease in mitochondrial respiration, and the
      loss of cellular levels of NAD+. Our study suggests that formation of
      peroxynitrite and subsequent activation of PARS may alter macrophage function in
      inflammatory processes and inhibition of nitric oxide, and that PARS may be a
      novel pharmacological approach to prevent cell injury in inflammation.

PMID- 9617883
TI  - Potential role of the peroxynitrate-poly(ADP-ribose) synthetase pathway in a rat
      model of severe hemorrhagic shock.
AB  - Peroxynitrite (a potent oxidant produced by nitric oxide and superoxide) and
      hydroxyl radical, reactive oxidants produced during hemorrhagic shock, are potent
      triggers of DNA single-strand breakage. DNA injury triggers the activation of the
      nuclear enzyme poly(ADP-ribose) synthetase (PARS), which contributes to cellular
      injury. Hemorrhagic shock is associated with early vasomotor paralysis as well as
      with early derangements in the cellular metabolic status. Here we have tested
      whether activation of PARS contributes to the vasodilatation and early mortality
      in a rat model of severe hemorrhagic shock. In anesthetized rats hemorrhaged to a
      mean arterial blood pressure of 35 mmHg, pretreatment with the PARS inhibitor 5
      iodo-6-amino-1,2-benzopyrone significantly improved survival rate. Furthermore,
      an inhibitor of nitric oxide biosynthesis (NG-methyl-L-arginine) and the cell
      permeable superoxide dismutase mimetic Mn(III)tetrakis(4-benzoic acid) porphyrin
      also offered a significant protection in terms of hypotension and acute
      mortality. However, the selective inhibitor of the inducible nitric oxide
      synthase, mercaptoethylguanidine, failed to affect blood pressure or mortality.
      The present data suggest that PARS activation plays a role in the pathophysiology
      of hemorrhagic shock. Early production of peroxynitrite (produced by nitric oxide
      from constitutive nitric oxide synthase) and hydroxyl radical may induce DNA
      single-strand breakage, which is the immediate trigger of PARS activation.

PMID- 9617884
TI  - Impact of dextran on microvascular disturbances and tissue injury following
      ischemia/reperfusion in striated muscle.
AB  - The aim of this study was to evaluate the effect of dextran (Dx) 1 versus Dx 60
      (molecular weights 1,000 and 60,000) on microvascular disturbances and tissue
      injury in striated muscle after ischemia/reperfusion (I/R). Experiments were
      performed using a 4 h pressure-induced ischemia model in the hamster dorsal
      skinfold chamber. Three groups (n=6) of animals received a continuous infusion
      (45 min, 3 microL/min) of either Dx 1 or Dx 60 (total dose 5 mg/kg) or saline
      solution beginning 15 min before reperfusion. Intravital fluorescence microscopy
      allowed for quantification of functional capillary density, leukocyte adherence,
      extravasation of fluorescein isothiocyanate-Dx, and nonviable (propidium
      positive) cell count before ischemia and .5, 2, and 24 h after reperfusion.
      Experiments were terminated with tissue preservation for electron microscopy.
      Postischemic functional capillary density was significantly improved by Dx 60 (at
      24 h, 88% vs. 51% in controls). In animals receiving postischemic Dx 1 or Dx 60,
      leukocyte adherence was significantly reduced (at .5 h, 44% and 58%,
      respectively) as compared with controls, whereas macromolecular extravasation was
      unchanged. Nonviable cell count was significantly decreased by both Dx fractions
      (at 24 h, Dx 1, 75%; Dx 60, 87%), indicating a reduction of tissue injury, which
      was also confirmed by electron microscopy. These results provide evidence that Dx
      60 at 5 mg/kg attenuates I/R injury more effectively than Dx 1. Leukocytes play a
      major role in the development of I/R injury, but macromolecular extravasation
      does not always correlate with the leukocyte-endothelium interaction and the
      manifestation of I/R injury.

PMID- 9617885
TI  - Cardiac contractility and structure are not significantly compromised even during
      the late, hypodynamic stage of sepsis.
AB  - Although cardiac function is depressed during endotoxic shock, it remains
      controversial whether the ventricular contractility and structure are altered
      during sepsis. To resolve this issue, rats were subjected to polymicrobial sepsis
      by cecal ligation and puncture (CLP). At 2, 5, and 10 h after CLP (i.e., the
      early, hyperdynamic stage of sepsis) or 20 h after CLP (the late, hypodynamic
      stage of sepsis, based on the depressed tissue perfusion), in vivo left
      ventricular contractility parameters such as maximal rate of the left ventricular
      pressure increase (+dP/dtmax) and decrease (-dP/dtmax), maximal rate of "pressure
      normalized" change in ventricular pressure (dP/dtmax/P), and ventricular peak
      systemic pressure were determined using a Digi-Med Heart Performance Analyzer. In
      additional groups of animals, ultrastructure of the cardiac muscle in the left
      ventricle was examined at 5, 10, or 20 h after CLP, using a transmission electron
      microscope. The results indicate that +dP/dtmax and dP/dtmax/P increased
      significantly at 2-10 h after CLP. The values of -dP/dtmax and ventricular peak
      systemic pressure increased significantly at 2 and 5 h after the onset of sepsis,
      respectively. These in vivo ventricular contractility parameters, however, were
      not significantly different from shams at 20 h after CLP. Ultrastructural
      examination showed that enlarged T-tubules were prominent during the hyperdynamic
      stage of sepsis, which was correlated with the increased cardiac contractility.
      Although focal and moderate hypertrophy as well as expanded intermyocyte
      junctions could be observed occasionally, myocardial cells did not appear to be
      compromised at 20 h after CLP. Thus, the transition from the hyperdynamic to
      hypodynamic circulation during sepsis does not appear to be due to any depression
      in myocardial function because cardiac contractility and structure are not
      compromised even during the late, hypodynamic stage of sepsis. However, further
      investigation is required to determine whether cardiac function is depressed at
      the terminal stage of polymicrobial sepsis.

PMID- 9617886
TI  - Suppressed thromboxane production in endotoxin-desensitized THP-1 cells is not a
      result of decreased prostaglandin H synthase activity.
AB  - Pre-exposure of THP-1 cells to low concentrations of endotoxin
      (lipopolysaccharide, LPS) down-regulates thromboxane (Tx) A2, an arachidonic acid
      (AA) metabolite, production in response to a subsequent LPS stimulation. To
      further delineate the mechanisms of LPS-induced down-regulation of TxA2, we
      examined expression of prostaglandin H synthase (PGHS)-2 mRNA, changes in PGHS
      activity, and content of PGHS-1 and -2. Pre-exposure to LPS (1 microg/mL for 18 h
      to desensitize cells) inhibits production of TxB2, the stable metabolite of TxA2,
      in response to secondary stimulation of LPS (10 microg/mL), when compared with
      LPS-stimulated naive cells (p < .05, n=5). LPS (10 microg/mL) induced expression
      of PGHS-2 mRNA at 1 and 2 h in naive cells, but this expression was decreased in
      the LPS-desensitized cells. However, exogenous AA (16 microM) or phorbol myristic
      acid (PMA), 3 microM) stimulated greater TxB2 production in the LPS-desensitized
      cells than in the naive cells (p < .05). Protein content of PGHS-1 and -2 were
      examined by Western blot analysis, using antibodies specific for PGHS-1 and PGHS
      2. Densitometric analysis demonstrated a significant increase in PGHS-2 induction
      in LPS-stimulated naive cells (405+/-174%) over its respective basal group (p <
      .05, n=5). PGHS-1 was constitutively present, but there was no significant
      difference in quantity between naive and LPS-desensitized basal or LPS-stimulated
      groups. Thus, despite the reduction in expression of PGHS-2 mRNA, these composite
      data demonstrate that down-regulation of PGHS activity (assessed with exogenous
      AA or PMA) cannot be responsible for the inhibition of AA metabolism observed in
      LPS desensitization.

PMID- 9617887
TI  - Etiology of metabolic acidosis during saline resuscitation in endotoxemia.
AB  - We sought to understand the mechanism of metabolic acidosis that results in acute
      resuscitated endotoxic shock. In six pentobarbital-anesthetized dogs, shock was
      induced by Escherichia coli endotoxin infusion (1 mg/kg) and was treated with
      saline infusion to maintain mean arterial pressure > 80 mmHg. Blood gases and
      strong ions were measured during control conditions and at 15, 45, 90, and 180
      min after endotoxin infusion. The mean saline requirement was 1833+/-523 mL over
      a 3 h period. The total acid load from each source was calculated using the
      standard base deficit. The mean arterial pH decreased from 7.32 to 7.11 (p <
      .01); pCO2 and lactate were unchanged. Saline accounted for 42% of the total acid
      load. However, 52% of the total acid load was unexplained. Although serum Na+ did
      not change, serum Cl-increased (127.7+/-5.1 mmol/L vs. 137.0+/-6.1 mmol/L;
      p=.016). We conclude that saline resuscitation alone accounts for more than one
      third of the acidosis seen in this canine model of acute endotoxemia, whereas
      lactate accounts for less than 10%. A large amount of the acid load can be
      attributed to differential Na+ and Cl- shifts from extravascular to vascular
      spaces.

PMID- 9617888
TI  - Altered systemic organ blood flow after combined injury with burn and smoke
      inhalation.
AB  - Systemic organ blood flow was longitudinally determined with fluorescent
      microspheres after severe thermal injury in unanesthetized sheep. After chronic
      instrumentation, 20 sheep were subjected to combined injury with 40% body surface
      area third-degree burn and 48 breaths of cotton smoke insufflation. During the
      next 72 h of the experimental period, all animals were resuscitated with Ringer's
      lactate following the Parkland formula. To test the effect of systemic
      administration of ibuprofen, animals were assigned to the control group (n=11) or
      the ibuprofen group (n=9). In the ibuprofen group, animals received ibuprofen as
      a 12 mg/kg bolus injection 1 h after injury and 6 mg/kg/h as a continuous
      infusion for the next 47 h. After this combined injury, animals exhibited a
      biphasic hemodynamic alteration, with an initial shock period and a later
      hyperdynamic period, a phenomenon often seen in severely burned patients. Among
      multiple organs, the splanchnic organs exhibited more dominant and sustained
      decreases in regional blood flow, whereas heart and kidney blood flow were
      maintained at more than 90% of baseline level even in the initial hypovolemic
      phase. In the postresuscitation period, no organ except the heart showed
      increased regional blood flow, despite a more than 20% increase in cardiac
      output. Ibuprofen had effects on early recovery from the initial shock period,
      and it improved intestinal organ blood flow, suggesting a potential benefit of
      this drug for severe thermal injury.

PMID- 9617889
TI  - Resuscitation with hypertonic saline dextran improves cardiac function in vivo
      and ex vivo after burn injury in sheep.
AB  - In a 24 h, double-blind, prospective trial, we tested the hypothesis that two 4
      mL/kg doses of hypertonic saline dextran (HSD; 7.5% NaCl/6% dextran 70) given in
      addition to isotonic fluid treatment would produce both immediate and sustained
      benefit for the heart after large burn injury. 12 instrumented sheep were
      subjected to a 40% total body surface area full-thickness flame burn under
      halothane anesthesia. 1 h after burn, when the animals had recovered from
      anesthesia, the first dose of either HSD (n=6) or normal saline (NaCl .9%; n=6)
      was infused over 30 min. The test solution was immediately followed by lactated
      Ringer's solution infused to maintain a urine output of 1-2 mL/kg x h throughout
      the study. The second dose of test solution was started at 12 h and was infused
      over 5 h. The initial dose of HSD corrected the burn-induced reduction in cardiac
      output, cardiac work, an index of myocardial contractility, and restored
      myocardial blood flow, as measured by the colored microsphere technique, to
      preburn values. Plasma concentrations of troponin I, creatine kinase (CK), and CK
      isoenzyme CKMB were increased 1 h after burn, but were not altered after HSD
      treatment. After euthanasia at 24 h, myocardial glutathione concentrations were
      higher in HSD-treated animals, whereas other markers of oxidative injury in heart
      or in plasma did not show systematic differences. The maximum contraction force
      measured in isolated right papillary muscles ex vivo was significantly greater in
      HSD-treated than normal saline-treated animals. In conclusion, the first dose of
      4 mL/kg HSD infused 1 h after burn improved cardiac function, whereas the second
      dose of HSD infused at 12 h was without apparent effect on dynamic variables. An
      overall effect of the HSD treatments was a lasting increase in papillary muscle
      contraction force.

PMID- 9617890
TI  - Nitric oxide in the liver may not be involved in blood redistribution during
      hemorrhagic shock in the dog.
AB  - We previously reported that nitric oxide (NO) in the brain cortex increases
      during hemorrhagic shock (HS) and then recovers to a baseline level by a
      retransfusion. Accordingly, we suggested that NO may play a role in blood
      redistribution during HS. To ascertain whether or not NO contributes to blood
      redistribution, we have investigated the changes in the liver's NO production
      during HS. Mongrel dogs were used in the study. After each dog was anesthetized
      with pentobarbital, an NO-selective electrode was placed in its liver, and a
      probe to measure hepatic blood flow (HF) was placed on the liver's surface. HS
      was induced until a mean arterial blood pressure of <40 mmHg was reached. In
      Group I (n=5), HS was maintained for 30 min. In Group II (n=7), shed blood was
      reinfused at 10 min after HS. In Group III (n=7), 10 min after NG-nitro-L
      arginine methyl ester 30 mg/kg intravenously (i.v.), the same procedures were
      performed as in Group II. In Groups II and III, although 10 min of HS produced an
      increase in NO-related electrical current [Group II, 2,197+/-786 pA; Group III,
      983+/-77 pA (mean+/-standard error)], reinfusion of shed blood restored the NO
      related electrical current to its baseline value. HF in Groups I and II decreased
      continuously during HS, and it recovered to baseline after the restoration from
      HS in Group II. In Group III, NG-nitro-L-arginine methyl ester 30 mg/kg i.v.
      decreased HF 12.7+/-.7 to 10.2+/-.6 mL/min/100 g (mean+/-standard error, p <
      .05). In conclusion, although NO produced in the liver might play an important
      pathophysiologic role in HS, it may not affect the blood redistribution during
      HS, such as in mean arterial blood pressure <40 mmHg.

PMID- 9617891
TI  - Biology of human umbilical cord blood-derived hematopoietic stem/progenitor
      cells.
AB  - Reported in 1989, studies by Broxmeyer, Gluckman, and colleagues demonstrated
      that umbilical cord blood (UCB) is a rich source of hematopoietic stem/progenitor
      cells (HSPC) and that UCB could be used in clinical settings for hematopoietic
      cell transplantation. Since then, a great interest has been generated on the
      biological characterization of these cells. Over the last nine years, several
      groups have focused on the study of UCB HSPC, addressing different aspects, such
      as the frequency of these cells in UCB, the identification of different HSPC
      subsets based on their immunophenotype, their ability to respond to hematopoietic
      cytokines, the factors that control their proliferation and expansion potentials,
      and their capacity to reconstitute hematopoiesis in animal models. Most of these
      studies have shown that significant functional differences exist between HSPC
      from UCB and adult bone marrow (i.e., the former possess higher proliferation and
      expansion potential than the latter). It is also noteworthy that genetic
      manipulation of UCB HSPC has been achieved by several groups and that genetically
      modified UCB cells have already been used in the clinic. In spite of the
      significant advances in the characterization of these cells, we are still in the
      process of trying to fully understand their biology, both at the cellular and the
      molecular levels. In the present article, we describe and discuss what is
      currently known about the biology of UCB HSPC.

PMID- 9617892
TI  - SCID mouse models of human stem cell engraftment.
AB  - The discovery of the severe combined immunodeficiency (scid) mouse mutation has
      provided a tool for establishment of small animal models as hosts for the in vivo
      analysis of normal and malignant human pluripotent hemopoietic stem cells.
      Intravenous injection of irradiated scid mice with human bone marrow, cord blood,
      or G-CSF cytokine-mobilized peripheral blood mononuclear cells, all rich in human
      hemopoietic stem cell activity, results in the engraftment of a human hemopoietic
      system in the murine recipient. This model has been used to identify a
      pluripotent stem cell, termed "scid-repopulating cell" (SRC) that is more
      primitive than any of the hemopoietic stem cell populations identified using the
      currently available in vitro methodology. In this review, we describe the
      development and use of this model system, termed Hu-SRC-SCID, and summarize the
      discoveries that have resulted from the investigation of human stem cells in this
      model. Finally, we detail the recent extension of the original Hu-SRC-SCID model
      system based on the C.B-17-scid mouse as the murine host to the Hu-SRC-NOD-SCID
      model based on the NOD-scid mouse as the host. The engraftment of human stem
      cells in the Hu-SRC-NOD-SCID model is enhanced over that observed in the Hu-SRC
      SCID model and results in exceptionally high levels of human hemopoietic cells in
      the murine recipient. Future directions to further improve the Hu-SRC-NOD-SCID
      model system and the potential utility of this model in the preclinical and
      diagnostic arenas of hematology and oncology are discussed.

PMID- 9617893
TI  - New perspectives on PKCtheta, a member of the novel subfamily of protein kinase
      C.
AB  - Members of the protein kinase C (PKC) family of serine/threonine protein kinases
      have been implicated in numerous cellular responses in a large variety of cell
      types. Expression patterns of individual members and differences in their
      cofactor requirements and potential substrate specificity suggest that each
      isoenzyme may be involved in specific regulatory processes. The PKCtheta
      isoenzyme exhibits a relatively restricted expression pattern with high protein
      levels found predominantly in hematopoietic cells and skeletal muscle. PKCtheta
      was found to be expressed in T, but not B lymphocytes, and to colocalize with the
      T-cell antigen receptor (TCR) at the site of contact between the antigen
      responding T cell and the antigen-presenting cell (APC). Colocalization of
      PKCtheta with the TCR was selective for this isoenzyme and occurred only upon
      antigen-mediated responses leading to T-cell activation and proliferation.
      PKCtheta was found to be involved in the regulation of transcriptional activation
      of early-activation genes, predominantly AP-1, and its cellular distribution and
      activation were found to be regulated by the 14-3-3 protein. Other findings
      indicated that PKCtheta can associate with the HIV negative factor (Nef) protein,
      suggesting that altered regulation of PKCtheta by Nef may contribute to the T
      cell impairments that are characteristic of infection by HIV. PKCtheta is
      expressed at relatively high levels in skeletal muscle, where it is suggested to
      play a role in signal transduction in both the developing and mature
      neuromuscular junction. In addition, PKCtheta appears to be involved in the
      insulin-mediated response of intact skeletal muscle, as well as in experimentally
      induced insulin resistance of skeletal muscle. Further studies suggest that
      PKCtheta is expressed in endothelial cells and is involved in multiple processes
      essential for angiogenesis and wound healing, including the regulation of cell
      cycle progression, formation and maintenance of actin cytoskeleton, and formation
      of capillary tubes. Here, we review recent progress in the study of PKCtheta and
      discuss its potential role in various cellular responses.

PMID- 9617894
TI  - Recombinant human growth hormone promotes hematopoietic reconstitution after
      syngeneic bone marrow transplantation in mice.
AB  - Recombinant human growth hormone (rhGH) was administered to mice after syngeneic
      bone marrow transplantation (BMT) to determine its effect on hematopoietic
      reconstitution. BALB/c mice were given 10 microg intraperitoneal injections of
      rhGH every other day for a total of 10 injections following syngeneic BMT. Mice
      that received rhGH exhibited significant increases in total hematopoietic
      progenitor cell content (colony-forming unit-culture) in both bone marrow and
      spleen. Erythroid cell progenitor content (burst-forming unit-erythroid) was also
      significantly increased after rhGH treatment. Analysis of peripheral blood
      indicated that administration of rhGH resulted in significant increases in the
      rate of white blood cell and platelet recovery. Granulocyte marker 8C5+ cells
      were also increased in the bone marrow and spleens of treated mice. Red blood
      cell, hematocrit, and hemoglobin levels were increased at all time points after
      rhGH treatment. No significant pathologic effects or weight gain were observed in
      mice receiving repeated injections of 10 microg rhGH. Thus, rhGH administration
      after syngeneic BMT promoted multilineage hematopoietic reconstitution and may be
      of clinical use for accelerating hematopoiesis after autologous BMT.

PMID- 9617895
TI  - The Raf-1 protein mediates insulin-like growth factor-induced proliferation of
      erythroid progenitor cells.
AB  - Previous studies from this and other laboratories have shown that insulin-like
      growth factor-1 (IGF-I) and insulin-like growth factor-2 (IGF-II) support
      erythroid colony formation in cultures supplemented with serum substitute and
      recombinant erythropoietin. Subpopulations of IGF-I- and IGF-II-dependent,
      erythropoietin-independent colony-forming unit-erythroid (CFU-E)-derived colonies
      and BFU-E-derived colonies were identified under serum-substituted conditions for
      adult bone-marrow-derived erythroid progenitors which proliferate in the absence
      and presence of exogenous anti-erythropoietin receptor monoclonal antibody and in
      serum-substituted medium that was preadsorbed with anti-erythropoietin IgG. To
      assess whether Raf-1 is required for the formation of IGF-dependent,
      erythropoietin-independent human erythroid colonies, 5-15 microM sense or
      antisense oligomer to raf-1 were added to serum-substituted cultures containing
      either 2 U/ml recombinant human erythropoietin (rHuEpo) alone or 0-1,000 ng/ml
      IGF-I or IGF-II with/without 2 U/ml rHuEpo. Both erythropoietin-induced and IGF
      induced erythroid colony formation were completely blocked by antisense (but not
      sense) oligomers to raf-1. Purified human CFU-Es were examined for Raf-1 message
      and protein. Total RNA was extracted, and raf-1 mRNA was detected on Northern
      blots. Furthermore, a 74 kD protein, corresponding to Raf-1, was also detected in
      CFU-Es purified from human adult sources. Together, these studies support the
      hypothesis that the Raf-1 protein mediates both erythropoietin-induced and IGF
      induced signal transduction in human erythroid progenitor cells.

PMID- 9617896
TI  - Mobilization of peripheral blood progenitor cells by Betafectin PGG-Glucan alone
      and in combination with granulocyte colony-stimulating factor.
AB  - Betafectin PGG-Glucan, a novel beta-(1,6) branched beta-(1,3) glucan purified
      from the cell walls of Saccharomyces cerevisiae, has been shown to synergize with
      myeloid growth factors in vitro and to enhance hematopoietic recovery in
      myelosuppressed mice and primates. Here we report that PGG-Glucan is also capable
      of mobilizing peripheral blood progenitor cells (PBPC). PGG-Glucan (0.5 mg/kg to
      16 mg/kg) was administered intravenously to C3H/HeN male mice and blood collected
      at times ranging from 30 min to seven days after injection. Based on granulocyte
      macrophage colony-forming cell (GM-CFC) levels, peak mobilization occurred 30 min
      after a 2 mg/kg PGG-Glucan dose. At this time GM-CFC numbers in PGG-Glucan
      treated mice were approximately fourfold greater than in saline-treated control
      mice. A second, smaller wave of GM-CFC mobilization (approximately twofold
      increase) also occurred on days 4 and 5 after PGG-Glucan treatment. Mobilization
      was not associated with the induction of alpha-chemokines, which have recently
      been reported to induce rapid progenitor cell mobilization. Competitive
      repopulation experiments performed in irradiated female C3H/HeN mice revealed
      that, at three months after transplantation, more male DNA was present in bone
      marrow, splenic, and thymic tissues from animals transplanted with cells obtained
      from mice 30 min after a 2 mg/kg PGG-Glucan dose than in tissues from animals
      transplanted with cells obtained from saline-treated mice. Additional experiments
      evaluated the mobilization effects of PGG-Glucan (2 mg/kg) administered to mice
      which had been pretreated for three consecutive days with G-CSF (125
      microg/kg/day). When blood was collected 30 min after PGG-Glucan treatment, the
      number of GM-CFC mobilized in combination-treated mice was additive between the
      number mobilized in mice treated with G-CSF alone and the number mobilized in
      mice treated with PGG-Glucan alone. These studies demonstrate that: A) PGG-Glucan
      can rapidly mobilize PBPC; B) the kinetic pattern of PGG-Glucan-induced
      mobilization is different from that of the CSFs; C) the reconstitutional
      potential of PGG-Glucan mobilized cells is greater than that of steady-state
      PBPC, and D) PGG-Glucan can enhance G-CSF-mediated PBPC mobilization.

PMID- 9617897
TI  - Special susceptibility to apoptosis of CD1a+ dendritic cell precursors
      differentiating from cord blood CD34+ progenitors.
AB  - We analyzed the effect of tumor necrosis factor (TNF)-alpha on the
      differentiation and viability of dendritic cells (DC) generated from cord blood
      CD34+ progenitors cultured for five days with GM-CSF, Flt-3 ligand (FL), and stem
      cell factor (SCF), and then with GM-CSF only [TNF(-) cultures]. Adding TNF-alpha
      from the start [TNF(+) cultures] potentiated progenitor cell proliferation and
      promoted early differentiation of CD1a+ DC precursors without affecting
      differentiation of CD14+ cells, which comprise bipotent precursors of DC and
      macrophages, nor of CD15+ granulocytic cells. Use of TNF-alpha was associated
      with increased cell mortality, which peaked on culture day 10 and mainly involved
      CD1a+ DC. Selective apoptosis of CD1a+ DC precursors was confirmed by showing
      that survival of day-7-sorted CD1a+CD14- cells from TNF(+) cultures was lower
      than that of CD1a-CD14+ cells. That similar findings were noted for sorted
      CD1a+CD14- cells of TNF(-) cultures, further cultured with GM-CSF without or with
      TNF-alpha, indicates that apoptosis of CD1a+ DC precursors was not induced by TNF
      alpha. Apoptosis of CD1a+ DC precursors occurred after the cells had lost the
      capacity to incorporate bromodeoxyuridin. Finally, using higher GM-CSF
      concentrations or adding interleukin 3 (IL-3) improved viability of CD1a+ cells.
      Other cytokines, such as IL-4 and transforming growth factor (TGF)-beta1, were
      ineffective in this respect, though they promoted differentiation of CD1a+ DC.
      These results indicate that TNF-alpha promotes the differentiation of CD1a+ DC
      precursors, which display a high susceptibility to apoptosis that can be
      prevented by high concentrations of GM-CSF or use of IL-3, without affecting the
      differentiation of the CD14+ DC precursors.

PMID- 9617899
TI  - Technical aspects of breast magnetic resonance imaging.
AB  - The appropriate role for magnetic resonance imaging (MRI) as an adjunct technique
      to mammography in the detection, diagnosis, staging, and therapy management of
      breast cancer has been the subject of much current research. The clinical
      application determines the choice of imaging technique. Time restraints due to
      the rapid kinetics of contrast enhancement require that trade-offs be made
      between spatial and temporal resolution, with a resulting effect on sensitivity
      and specificity. This article discusses some general requirements and
      recommendations for breast MRI techniques, including dedicated radiofrequency
      coils, pulse sequence specifications and image quality considerations, fat
      suppression techniques, methods of contrast administration, and image
      postprocessing and interpretation.

PMID- 9617898
TI  - Tyro 3 receptor tyrosine kinase and its ligand, Gas6, stimulate the function of
      osteoclasts.
AB  - Bone is continuously being formed and resorbed. This process is accomplished by
      the precise coordination of two cell types: osteoblasts and osteoclasts.
      Osteoclasts are large, multinucleated cells that are derived from the same
      hematopoietic precursors as macrophages. However, these bone-resorbing cells are
      difficult to study directly because of their relative inaccessibility. The
      purification of primary osteoclasts from rabbit bones by their adherent nature
      provides an opportunity for investigating the molecules in osteoclasts. We have
      examined the expression of receptor tyrosine kinase by polymerase chain reaction
      (PCR) and found that Tyro 3 was frequently identified from primary osteoclasts in
      PCR cloning. Immunohistochemistry revealed that Tyro 3 was expressed on the
      multinucleated osteoclasts which were positive for tartrate-resistant acid
      phosphatase (TRAP), but not on mononuclear TRAP-positive cells. The Tyro 3
      ligand, Gas6, induced the phosphorylation of Tyro 3 receptors in osteoclasts in
      two to five min. Gas6 and protein S directly enhanced the bone resorbing activity
      of mature osteoclasts. This effect of Gas6 was inhibited by the addition of a
      tyrosine kinase inhibitor, herbimycin A. However, Gas6 did not affect the
      differentiation of osteoclasts from bone marrow cells. Gas6 and protein S are
      dependent on vitamin K, a cofactor for the enzyme responsible for carboxylation
      of glutamic acid residues. The findings in this study are the first to indicate a
      new biological activity of Gas6 and protein S as a direct regulator of
      osteoclastic function; they give an insight into the role of these vitamin K
      dependent ligands in bone resorption in vivo.

PMID- 9617900
TI  - Contrast-enhanced magnetic resonance imaging of the breast: interpretation
      guidelines.
AB  - In the past decade, most studies have shown that in selected indications of
      breast imaging, the overall accuracy can be improved by the additional use of
      contrast-enhanced magnetic resonance imaging (MRI). The sensitivity of contrast
      enhanced MRI for invasive malignancy is >98%; reported specificity, however,
      ranges from 37% to 97%. This range of values is predominantly caused by different
      patient preselection and interpretation criteria. Other factors, such as
      technique (e.g., choice of pulse sequence and echo time, slice thickness,
      reduction in artifacts, dosage of contrast agent, and methods for elimination of
      fat signal), hormonal influences (menstrual cycle and hormonal replacement
      therapy), and levels of verification, influence the accuracy and reproducibility
      of contrast-enhanced MRI. An appropriate application of MRI is highly desirable
      because of the increased costs of imaging, increased rates of biopsy due to false
      positive results, and possibility of false-negative results caused by technical
      failures and interpretation errors. We present an overview of the sensible
      application and interpretation of contrast-enhanced MRI of the breast based on
      our experience and on published data.

PMID- 9617901
TI  - Magnetic resonance guided localization and biopsy of suspicious breast lesions.
AB  - Contrast-enhanced magnetic resonance imaging (MRI) is being used increasingly as
      a complementary diagnostic modality in breast imaging of preselected patients.
      The exclusion of multicentricity before surgery and the differentiation between a
      scar and a carcinoma are well-accepted indications of this method. Problems
      result when suspicious lesions found with MRI cannot be visualized with
      mammography or ultrasonography. In these cases, MRI-based guidance systems are
      needed to guide needle biopsy or allow localization of the lesion before surgery.
      At our institution, 167 MR-guided interventions (35 percutaneous biopsies and 132
      preoperative localizations) have been performed with the use of different types
      of add-on devices during the past 3 years. Percutaneous biopsy (31 fine needle
      aspiration and four core biopsies) revealed 24 benign and 8 malignant lesions, 3
      biopsies were insufficient. Histologic examination after MR-guided wire
      localization showed benign findings in 68 lesions (52%) and malignancy in 64
      lesions (48%). Technical aspects, experiences, advantages, and disadvantages of
      our system as well as those of other devices are reported and discussed. MR
      compatible equipment for interventions of the breast is demonstrated. In
      conclusion, we perform MR-guided interventions of the breast routinely in
      indicated cases at a rate of approximately 3-5% for all patients undergoing
      diagnostic contrast-enhanced MRI of the breast.

PMID- 9617902
TI  - Magnetic resonance imaging in breast cancer staging.
AB  - For many solid carcinomas, high-resolution cross-sectional imaging has changed
      cancer staging, the evaluation of therapeutic response, the detection of
      recurrence, and even how therapy is selected and performed. Such imaging has not
      yet had similar effects on breast cancer. Evaluations of therapeutic response in
      breast carcinomas have been impeded by the current limited methods of evaluating
      breast tumor size and extent: clinical palpation, ultrasonography, and
      mammography. The use of magnetic resonance imaging (MRI) of the breast in the
      evaluation of breast tumors brings the advantages of high-resolution cross
      sectional imaging to breast cancer staging and treatment evaluation and is likely
      to greatly enhance research efforts in this complex disease. MRI of the breast
      has evolved to be the most accurate noninvasive technique for local staging of
      breast cancer. MRI is most accurate in measuring tumor size and detecting
      multicentric disease. These staging characteristics affect the selection of
      therapy and initial determination of prognosis; therefore, MRI of the breast can
      change the assessment of fundamental parameters on which treatment is selected.
      Because clinical trials of new cancer treatments are predicated on proper and
      accurate characterization of the tumor, MRI also should affect how clinical
      trials are performed and evaluated.

PMID- 9617903
TI  - Cross-reference weighted least square estimates for positron emission tomography.
AB  - An efficient new method, termed as the cross-reference weighted least square
      estimate (WLSE) [CRWLSE], is proposed to integrate the incomplete local
      smoothness information to improve the reconstruction of positron emission
      tomography (PET) images in the presence of accidental coincidence events and
      attenuation. The algebraic reconstruction technique (ART) is applied to this new
      estimate and the convergence is proved. This numerical technique is based on row
      operations. The computational complexity is only linear in the sizes of pixels
      and detector tubes. Hence, it is efficient in storage and computation for a large
      and sparse system. Moreover, the easy incorporation of range limits and spatially
      variant penalty will not deprive the efficiency. All this makes the new method
      practically applicable. An automatically data-driven selection method for this
      new estimate based on the generalized cross validation is also studied. The Monte
      Carlo studies demonstrate the advantages of this new method.

PMID- 9617904
TI  - Noise characteristics of 3-D and 2-D PET images.
AB  - We analyzed the noise characteristics of two-dimensional (2-D) and three
      dimensional (3-D) images obtained from the GE Advance positron emission
      tomography (PET) scanner. Three phantoms were used: a uniform 20-cm phantom, a 3
      D Hoffman brain phantom, and a chest phantom with heart and lung inserts. Using
      gated acquisition, we acquired 20 statistically equivalent scans of each phantom
      in 2-D and 3-D modes at several activity levels. From these data, we calculated
      pixel normalized standard deviations (NSD's), scaled to phantom mean, across the
      replicate scans, which allowed us to characterize the radial and axial
      distributions of pixel noise. We also performed sequential measurements of the
      phantoms in 2-D and 3-D modes to measure noise (from interpixel standard
      deviations) as a function of activity. To compensate for the difference in axial
      slice width between 2-D and 3-D images (due to the septa and reconstruction
      effects), we developed a smoothing kernel to apply to the 2-D data. After
      matching the resolution, the ratio of image-derived NSD values (NSD2D/NSD3D)2
      averaged throughout the uniform phantom was in good agreement with the noise
      equivalent count (NEC) ratio (NEC3D/NEC2D). By comparing different phantoms, we
      showed that the attenuation and emission distributions influence the spatial
      noise distribution. The estimates of pixel noise for 2-D and 3-D images produced
      here can be applied in the weighting of PET kinetic data and may be useful in the
      design of optimal dose and scanning requirements for PET studies. The accuracy of
      these phantom-based noise formulas should be validated for any given imaging
      situation, particularly in 3-D, if there is significant activity outside the
      scanner field of view.

PMID- 9617905
TI  - Projection space image reconstruction using strip functions to calculate pixels
      more "natural" for modeling the geometric response of the SPECT collimator.
AB  - The spatially varying geometric response of the collimator-detector system in
      single photon emission computed tomography (SPECT) causes loss in resolution,
      shape distortions, reconstructed density nonuniformity, and quantitative
      inaccuracies. A projection space image reconstruction algorithm is used to
      correct these reconstruction artifacts. The projectors F use strip functions to
      calculate pixels more "natural" for modeling the two-dimensional (2-D) geometric
      response of the SPECT collimator transaxially to the axis of rotation. These
      projectors are defined by summing the intersection of an array of multiple strips
      rotated at equal angles to approximate the ideal system geometric response of the
      collimator. Two projection models were evaluated for modeling the system
      geometric response function. For one projector each strip is of equal weight, for
      the other projector a Gaussian weighting is used. Parallel beam and fan beam
      projections of a physical three-dimensional (3-D) Hoffman brain phantom and a
      Jaszczak cold rod phantom were used to evaluate the geometric response
      correction. Reconstructions were obtained by using the singular value
      decomposition (SVD) method and the iterative conjugate gradient algorithm to
      solve for q in the imaging equation FGq = p, where p is the projection
      measurement. The projector F included the new models for the geometric response,
      whereas, the backprojector G did not always model the geometric response in order
      to increase the computational speed. The final reconstruction was obtained by
      sampling the backprojection Gq at a discrete array of points. Reconstructions
      produced by the two proposed projectors showed improved resolution when compared
      against a unit-strip "natural" pixel model, the conventional image pixelized
      model with ray tracing to calculate the geometric response, and the filtered
      backprojection algorithm. When the reconstruction is displayed on fine grid
      points, the continuity and resolution of the image is preserved without the ring
      artifacts seen in the unit-strip "natural" pixel model. With present computing
      power, the geometric response correction using the proposed projection space
      reconstruction approach is not yet feasible for routine clinical use.

PMID- 9617906
TI  - Automatic detection of the boundary of the calcaneus from ultrasound parametric
      images using an active contour model; clinical assessment.
AB  - This paper presents a computerized method for automated detection of the boundary
      of the os calcis on in vivo ultrasound parametric images, using an active dynamic
      contour model. The initial contour, defined without user interaction, is an iso
      contour extracted from the textural feature space. The contour is deformed
      through the action of internal and external forces, until stability is reached.
      The external forces, which characterize image features, are a combination of gray
      level information and second-order textural features arising from local
      cooccurrence matrices. The broadband ultrasound attenuation (BUA) value is then
      averaged within the contour obtained. The method was applied to 381 clinical
      images. The contour was correctly detected in the great majority of the cases.
      For the short-term reproducibility study, the mean coefficient of variation was
      equal to 1.81% for BUA values and 4.95% for areas in the detected region. Women
      with osteoporosis had a lower BUA than age-matched controls (p = 0.0005). In
      healthy women, the age-related decline was -0.45 dB/MHz/yr. In the group of
      healthy post-menopausal women, years since menopause, weight and age were
      significant predictors of BUA. These results are comparable to those obtained
      when averaging BUA values in a small region of interest.

PMID- 9617907
TI  - Errors in biased estimators for parametric ultrasonic imaging.
AB  - Maximum likelihood (ML) methods are widely used in acoustic parameter estimation.
      Although ML methods are often unbiased, the variance is unacceptably large for
      many applications, including medical imaging. For such cases, Bayesian estimators
      can reduce variance and preserve contrast at the cost of an increased bias.
      Consequently, including prior knowledge about object and noise properties in the
      estimator can improve low-contrast target detectability of parametric ultrasound
      images by improving the precision of the estimates. In this paper, errors
      introduced by biased estimators are analyzed and approximate closed-form
      expressions are developed. The task-specific nature of the estimator performance
      is demonstrated through analysis, simulation, and experimentation. A strategy for
      selecting object priors is proposed. Acoustic scattering from kidney tissue is
      the emphasis of this paper, although the results are more generally applicable.

PMID- 9617908
TI  - Standardization in the field of medical image management: the contribution of the
      MIMOSA model.
AB  - This paper deals with the development of standards in the field of medical
      imaging and picture archiving and communication systems (PACS's), and notably
      concerning the interworking between PACS's and hospital information systems
      (HIS). It explains, in detail, how a conceptual model of the management of
      medical images, such as the medical image management in an open system
      architecture (MIMOSA) model, can contribute to the development of standards for
      medical image management and PACS's. This contribution is twofold: 1) Since the
      model lists and structures the concepts and resources involved to make the images
      available to the users when and where they are required, and describes the
      interactions between PACS components and HIS, the MIMOSA work helps by defining a
      reference architecture which includes an external description of the various
      components of a PACS, and a logical structure for assembling them. 2) The model
      and the implementation of a demonstrator based on this model allow the relevance
      of the Digital Imaging and Communications in Medicine (DICOM) standard with
      respect to image management issues to be assessed, highlighting some current
      limitations of this standard and proposing extensions. Such a twofold action is
      necessary in order both to bring solutions, even partial, in the short term, and
      to allow for the convergence, in the long term, of the standards developed by
      independent standardization groups in medical informatics (e.g., those within
      Technical Committee 251 of CEN: Comite Europeen de Normalisation).

PMID- 9617910
TI  - A nonparametric method for automatic correction of intensity nonuniformity in MRI
      data.
AB  - A novel approach to correcting for intensity nonuniformity in magnetic resonance
      (MR) data is described that achieves high performance without requiring a model
      of the tissue classes present. The method has the advantage that it can be
      applied at an early stage in an automated data analysis, before a tissue model is
      available. Described as nonparametric nonuniform intensity normalization (N3),
      the method is independent of pulse sequence and insensitive to pathological data
      that might otherwise violate model assumptions. To eliminate the dependence of
      the field estimate on anatomy, an iterative approach is employed to estimate both
      the multiplicative bias field and the distribution of the true tissue
      intensities. The performance of this method is evaluated using both real and
      simulated MR data.

PMID- 9617909
TI  - Partial-volume Bayesian classification of material mixtures in MR volume data
      using voxel histograms.
AB  - We present a new algorithm for identifying the distribution of different material
      types in volumetric datasets such as those produced with magnetic resonance
      imaging (MRI) or computed tomography (CT). Because we allow for mixtures of
      materials and treat voxels as regions, our technique reduces errors that other
      classification techniques can create along boundaries between materials and is
      particularly useful for creating accurate geometric models and renderings from
      volume data. It also has the potential to make volume measurements more
      accurately and classifies noisy, low-resolution data well. There are two unusual
      aspects to our approach. First, we assume that, due to partial-volume effects, or
      blurring, voxels can contain more than one material, e.g., both muscle and fat;
      we compute the relative proportion of each material in the voxels. Second, we
      incorporate information from neighboring voxels into the classification process
      by reconstructing a continuous function, rho(x), from the samples and then
      looking at the distribution of values that rho(x) takes on within the region of a
      voxel. This distribution of values is represented by a histogram taken over the
      region of the voxel; the mixture of materials that those values measure is
      identified within the voxel using a probabilistic Bayesian approach that matches
      the histogram by finding the mixture of materials within each voxel most likely
      to have created the histogram. The size of regions that we classify is chosen to
      match the spacing of the samples because the spacing is intrinsically related to
      the minimum feature size that the reconstructed continuous function can
      represent.

PMID- 9617911
TI  - Fully automatic segmentation of the brain in MRI.
AB  - A robust fully automatic method for segmenting the brain from head magnetic
      resonance (MR) images has been developed, which works even in the presence of
      radio frequency (RF) inhomogeneities. It has been successful in segmenting the
      brain in every slice from head images acquired from several different MRI
      scanners, using different-resolution images and different echo sequences. The
      method uses an integrated approach which employs image processing techniques
      based on anisotropic filters and "snakes" contouring techniques, and a priori
      knowledge, which is used to remove the eyes, which are tricky to remove based on
      image intensity alone. It is a multistage process, involving first removal of the
      background noise leaving a head mask, then finding a rough outline of the brain,
      then refinement of the rough brain outline to a final mask. The paper describes
      the main features of the method, and gives results for some brain studies.

PMID- 9617912
TI  - Derivation of optimal filters for the detection of coronary arteries.
AB  - In this paper optimal filters for the detection of coronary arteries with a
      diameter range of 0.5-6.0 mm in digital X-ray images are derived using a
      computational approach. This approach is based on the two requirements for
      optimal detection. First, the filter should maximize the number of detected true
      edges and minimize the number of detected false edges. Second, if an edge has
      been detected, its position should be as close as possible to the true edge
      position in the image. Since the grey value profile in a digital X-ray image
      associated with an arterial vessel is asymmetric, the theory on edge detection
      derived by Canny has been expanded with two additional boundary constraints to
      make it suitable for the derivation of filters for asymmetric edges. It is
      demonstrated that it is possible to derive optimal filters for coronary segments.
      The localization error, defined by the square root of the sum of the squared
      systematic and random errors in the assessment of the arterial diameter, depends
      on the size of the coronary artery and the amount of noise in the image. In this
      paper, an evaluation study is described to assess the relationship between
      localization error and the amount of noise upon the vessel profile. For that
      purpose, an analytical description of the vessel profile in an angiographic image
      was derived. For the larger arteries the relation between noise and localization
      error was found to be linear and no systematic over- or underestimations were
      observed, even if the noise level was very high. However, it can be shown that
      the smallest diameter that can be measured depends on the amount of noise present
      in the data. Even for images that contain only a low amount of noise, arterial
      diameters below 0.7 mm cannot be measured accurately. If the noise in the image
      increases, the lowest measurable arterial diameter value also increases. Also the
      random error increases rapidly for vessel diameters below 1.2 mm, but with a
      limited amount of noise and a diameter value above 0.7 mm the random error is
      still acceptable [0.15 mm (21%) for 0.7-mm vessels, 0.06 mm (6%) for 1-mm
      vessels].

PMID- 9617913
TI  - A viewpoint determination system for stenosis diagnosis and quantification in
      coronary angiographic image acquisition.
AB  - This paper describes the usefulness of computer assistance in the acquisition of
      "good" images for stenosis diagnosis and quantification in coronary angiography.
      The system recommends the optimal viewpoints from which stenotic lesions can be
      observed clearly based on images obtained from initial viewpoints. First, the
      viewpoint dependency of the apparent severity of a stenotic lesion is
      experimentally analyzed using software phantoms in order to show the seriousness
      of the problem. The implementation of the viewpoint determination system is then
      described. The system provides good user-interactive tools for the semiautomated
      estimation of the orientation and diameter of stenotic segments and the three
      dimensional (3-D) reconstruction of vessel structures. Using these tools,
      viewpoints that will not give rise to foreshortening and vessel overlap can be
      efficiently determined. Experiments using real coronary angiograms show the
      system to be capable of the reliable diagnosis and quantification of stenosis.

PMID- 9617914
TI  - Nitric oxide-producing neurons in the neocortex: morphological and functional
      relationship with intraparenchymal microvasculature.
AB  - Nitric oxide is a ubiquitous intercellular messenger involved in particular
      functions in the cardiovascular, immunological and nervous systems. In the
      cerebral cortex, nitric oxide is synthetized by endothelial cells and by a
      discrete population of neurons and glial cells expressing nitric oxide synthase.
      Nitric oxide of endothelial and neuronal origin is involved in the regulation of
      cerebral blood flow. In this review, we have tried to combine morphological data
      providing information on the chemical nature of nitric oxide synthase-containing
      neurons and their arrangement, especially in relation to intracortical blood
      vessels, with functional results suggesting the participation of these neurons in
      the coupling between local cortical blood flow and synaptic activity.

PMID- 9617915
TI  - A local circuit approach to understanding integration of long-range inputs in
      primary visual cortex.
AB  - Integration of inputs by cortical neurons provides the basis for the complex
      information processing performed in the cerebral cortex. Here, we have examined
      how primary visual cortical neurons integrate classical and nonclassical
      receptive field inputs. The effect of nonclassical receptive field stimuli and,
      correspondingly, of long-range intracortical inputs is known to be context
      dependent: the same long-range stimulus can either facilitate or suppress
      responses, depending on the level of local activation. By constructing a large
      scale model of primary visual cortex, we demonstrate that this effect can be
      understood in terms of the local cortical circuitry. Each receptive field
      position contributes both excitatory and inhibitory inputs; however, the
      inhibitory inputs have greater influence when overall receptive field drive is
      greater. This mechanism also explains contrast-dependent modulations within the
      classical receptive field, which similarly switch between excitatory and
      inhibitory. In order to simplify analysis and to explain the fundamental
      mechanisms of the model, self-contained modules that capture nonlinear local
      circuit interactions are constructed. This work supports the notion that
      receptive field integration is the result of local processing within small groups
      of neurons rather than in single neurons.

PMID- 9617916
TI  - Opposing roles for dopamine and serotonin in the modulation of human spatial
      working memory functions.
AB  - Neurocognitive research has focused on monoaminergic influences over broad
      behavior patterns. For example, dopamine (DA) generally facilitates informational
      transfer within limbic and cortical networks to promote reward-seeking behavior.
      Specifically, DA activity in prefrontal cortex modulates the ability for nonhuman
      primates and humans to perform spatial working memory tasks. Serotonin (5HT)
      constrains the activity of DA, resulting in an opposing relationship between DA
      and 5HT with respect to emotional and motor behaviors. A role for 5HT in
      constraining prefrontally guided spatial working memory (WM) processes in humans
      has not been empirically demonstrated but is a logical avenue for study if these
      principles of neurotransmitter activity hold within cortical networks. In this
      study, normal humans completed a visuospatial WM task under pharmacological
      challenge with (i) bromocriptine, a DA agonist and (ii) fenfluramine, a serotonin
      agonist, in a double-blind, repeated-measures, placebo-controlled design.
      Findings indicate that bromocriptine facilitated spatial delayed, but not
      immediate, memory performance. Fenfluramine resulted in impaired delayed spatial
      memory. These effects were not due to nonspecific arousal, attentional,
      sensorimotor or perceptual changes. These findings suggest that monoaminergic
      neurotransmitters (DA and 5HT) may interact within cortical networks to modulate
      the expression of specific cognitive behaviors, particularly effortful processes
      associated with goal-directed activity.

PMID- 9617917
TI  - A histologically visible representation of the fingers and palm in primate area
      3b and its immutability following long-term deafferentations.
AB  - An isomorph of the glabrous hand is visible in primary somato-sensory cortex
      (area 3b) of owl monkeys in brain sections cut parallel to the surface and
      stained for myelin. A mediolateral row of five ovals, separated by myelin-light
      septa, represents digits and corresponds precisely with cortical sites activated
      by light touch on individual digits in microelectrode recordings. A number of
      caudal ovals relate to pads of the palm. A more distinct septum separates the
      hand from the more lateral face representation. Within the face representation,
      two large myelin-dense ovals can be identified that are activated by the upper or
      lower face in a caudo-rostral sequence. Accidental finger loss or dorsal column
      section, deafferentations that result in reorganization of the physiological map
      in area 3b, do not alter the morphological map. The proportions for each digit
      and palm in the morphological map do not vary across normal and deafferented
      animals. Similar isomorphs were also seen in area 3b of squirrel and macaque
      monkeys. We conclude that the anatomical isomorph for the body surface
      representation in area 3b is a reliable reflection of normal cortical
      organization and may be a common feature of the primate area 3b. The isomorph can
      provide a reference in studies of somatotopic reorganization.

PMID- 9617918
TI  - Spacing of cytochrome oxidase blobs in visual cortex of normal and strabismic
      monkeys.
AB  - Some models of visual cortical development are based on the assumption that the
      tangential organization of V1 is not determined prior to visual experience. In
      these models, correlated binocular activity is a key element in the formation of
      visual cortical columns, and when the degree of interocular correlation is
      reduced the models predict an increase in column spacing. To examine this
      prediction we measured the spacing of columns, as defined by cytochrome oxidase
      (CO) blobs, in the visual cortex of monkeys whose binocular vision was either
      normal or disrupted by a strabismus. The spatial distribution of blobs was
      examined in seven normal and five strabismic macaques. Tangential sections
      through the upper layers of the visual cortex were stained to reveal the two
      dimensional (2D) pattern of CO blobs. Each blob was localized and their center-to
      center spacing, packing arrangement and density were calculated using 2D nearest
      neighbor spatial analyses. The mean center-to-center spacing of blobs (590 microm
      for normally reared and 598 microm for strabismic macaques) and the mean density
      of blobs (3.67 blobs/mm2 for normally reared and 3.45 blobs/mm2 for strabismic
      macaques) were not significantly different. In addition, the 2D packing
      arrangement of the blobs was not affected by strabismus. While it is clear that
      neural activity plays a key role in the elaboration and refinement of ocular
      dominance cortical modules, we conclude that it does not determine the spatial
      period of the pattern of CO blobs. This suggests that aspects of the neural
      circuitry underlying the columnar architecture of the visual cortex are
      established prenatally and its fundamental periodicity is not modifiable by
      experience.

PMID- 9617919
TI  - Synaptogenesis in layer I of the human cerebral cortex in the first half of
      gestation.
AB  - The formation of synapses is among the most important steps in neuronal
      differentiation and the establishment of neuronal circuits. To establish baseline
      data about the time of onset, density and the course of synaptic formation in
      different regions of the human cerebral cortex before birth, synaptogenesis in
      layer I was examined by electron microscopy in fetuses ranging in age from 6 to
      24 gestational weeks. Synapses were first observed in the primordial plexiform
      layer (marginal zone) in both the lateral and medial cerebral walls between the
      6th and 7th gestational week, before the formation of the cortical plate. The
      density of synapses increased rapidly after the formation of the cortical plate,
      increasing by 37% between 12 and 14 weeks. Synaptogenesis proceeded at the same
      rate in the lateral and occipital cortex during this period. Further, with one
      exception, the insular region, synaptic density was comparable in prospective
      areas of prefrontal, motor, visual, temporal and cingulate cortex in a group of
      fetuses at midgestation (20 weeks). The results are consistent with a synchronous
      course of synaptogenesis of the neocortex.

PMID- 9617920
TI  - Activation of the human occipital and parietal cortex by pattern and luminance
      stimuli: neuromagnetic measurements.
AB  - We compared cortical reactivity to pattern and luminance stimuli by recording
      evoked responses and spontaneous brain rhythms from 10 subjects with a whole
      scalp neuromagnetometer. Hemifield patterns (black-and-white checkerboards)
      elicited strong contralateral transient activation of the occipital V1/V2 cortex,
      maximum at 65-75 ms, followed by sustained activation during the 2 s stimulus.
      Responses to hemifield luminance stimuli also had an occipital component, but
      they were dominated by activation of the medial parieto-occipital sulcus (POS) 60
      70 ms later. The POS region was equally well activated by foveal and extrafoveal
      stimuli. The occipital responses to hemifield luminance stimuli differed from
      those to pattern stimuli in two main aspects: the sustained activation was
      significantly weaker, and the responses were almost symmetrical, indicating a
      surprisingly bilateral occipital activation. These effects were similar with
      foveal and extrafoveal stimuli. The spontaneous 10 Hz alpha rhythm, originating
      predominantly in the POS region, was suppressed after both stimulus onsets and
      offsets, more strongly for luminance than pattern stimuli. Activation of the
      occipital cortex dominated after pattern stimuli, whereas the effect of luminance
      stimulation was stronger in the parieto-occipital region. The distinct signal
      distributions in the occipital and POS regions suggest that the two types of
      stimuli activate the magno- and parvocellular pathways to a varying degree. These
      findings are also in line with a stronger attention-catching value of the
      luminance than pattern stimuli.

PMID- 9617921
TI  - SNAP-25 deficit and hippocampal connectivity in schizophrenia.
AB  - Regional abnormalities of brain connectivity may be an important substrate for
      the expression of schizophrenia, a severe form of mental illness. Brain imaging
      and postmortem morphometric studies indicate hippocampal structure is abnormal in
      schizophrenia. To study molecular components of hippocampal connectivity the
      presynaptic proteins SNAP-25 and synaptophysin were assayed in postmortem
      samples. Immunocytochemical studies indicated reduced SNAP-25 immunoreactivity in
      schizophrenia compared to controls, particularly in the terminal fields of
      entorhinal cortex projections. Although there were no overall changes in
      synaptophysin immunoreactivity, in the granule cell layer of the dentate gyrus
      synaptophysin immunoreactivity was increased in schizophrenia. These results
      indicate that disconnection of a subset of hippocampal circuitry from the
      entorhinal cortex, as well as intrinsic changes in hippocampal connectivity, may
      contribute to the mechanism of illness in schizophrenia.

PMID- 9617922
TI  - Cellular and subcellular sites for noradrenergic action in the monkey
      dorsolateral prefrontal cortex as revealed by the immunocytochemical localization
      of noradrenergic receptors and axons.
AB  - A series of electron microscopic immunocytochemical studies was performed to
      analyze subcellular sites for noradrenergic modulation in monkey prefrontal
      cortex. One out of 12 noradrenergic varicosities, identified by dopamine beta
      hydroxylase immunocytochemistry within single ultrathin sections, forms
      morphologically identifiable junctions with small dendrites and spines.
      Accordingly, alpha2-adrenergic receptors, almost all of which are of the A
      subtype, that occur in spines are localized discretely over postsynaptic
      membranes. alpha2-Adrenergic receptors are also found at sites along axons,
      dendritic shafts and astrocytic processes lacking morphologically identifiable
      synaptic junctions, suggesting that these receptors are activated by volume
      transmission. In particular, axonal alpha2-adrenergic receptors occur mostly at
      pre-terminal regions, suggesting that axo-axonic interactions may mediate
      reduction of neurotransmitter release at sites other than axo-spinous junctions
      by closing voltage-dependent calcium channels. These results indicate that
      noradrenergic modulation of prefrontal cortex involves synaptic interactions at
      spines of pyramidal neurons and nonsynaptic volume transmission to glia,
      dendritic shafts and axons.

PMID- 9617923
TI  - Morphological variation of layer III pyramidal neurones in the occipitotemporal
      pathway of the macaque monkey visual cortex.
AB  - We compared the morphological characteristics of layer III pyramidal neurones in
      different visual areas of the occipitotemporal cortical 'stream', which processes
      information related to object recognition in the visual field (including shape,
      colour and texture). Pyramidal cells were intracellularly injected with Lucifer
      Yellow in cortical slices cut tangential to the cortical layers, allowing
      quantitative comparisons of dendritic field morphology, spine density and cell
      body size between the blobs and interblobs of the primary visual area (V1), the
      interstripe compartments of the second visual area (V2), the fourth visual area
      (V4) and cytoarchitectonic area TEO. We found that the tangential dimension of
      basal dendritic fields of layer III pyramidal neurones increases from caudal to
      rostral visual areas in the occipitotemporal pathway, such that TEO cells have,
      on average, dendritic fields spanning an area 5-6 times larger than V1 cells. In
      addition, the data indicate that V1 cells located within blobs have significantly
      larger dendritic fields than those of interblob cells. Sholl analysis of
      dendritic fields demonstrated that pyramidal cells in V4 and TEO are more complex
      (i.e. exhibit a larger number of branches at comparable distances from the cell
      body) than cells in V1 or V2. Moreover, this analysis demonstrated that the
      dendrites of many cells in V1 cluster along specific axes, while this tendency is
      less marked in extrastriate areas. Most notably, there is a relatively large
      proportion of neurones with 'morphologically orientation-biased' dendritic fields
      (i.e. branches tend to cluster along two diametrically opposed directions from
      the cell body) in the interblobs in V1, as compared with the blobs in V1 and
      extrastriate areas. Finally, counts of dendritic spines along the length of basal
      dendrites revealed similar peak spine densities in the blobs and the interblobs
      of V1 and in the V2 interstripes, but markedly higher spine densities in V4 and
      TEO. Estimates of the number of dendritic spines on the basal dendritic fields of
      layer III pyramidal cells indicate that cells in V2 have on average twice as many
      spines as V1 cells, that V4 cells have 3.8 times as many spines as V1 cells, and
      that TEO cells have 7.5 times as many spines as V1 cells. These findings suggest
      the possibility that the complex response properties of neurones in rostral
      stations in the occipitotemporal pathway may, in part, be attributed to their
      larger and more complex basal dendritic fields, and to the increase in both
      number and density of spines on their basal dendrites.

PMID- 9617924
TI  - Bone conduction impairment in uncomplicated chronic suppurative otitis media.
AB  - PURPOSE: To study the effect of uncomplicated chronic suppurative otitis media on
      bone conduction thresholds and its relationship to the disease type and duration.
      PATIENTS AND METHODS: The differences in bone conduction thresholds of diseased
      and contralateral ears were compared in 218 patients with unilateral
      uncomplicated chronic suppurative otitis media. Pure tone audiometry was carried
      out after successful surgery on 93 patients. RESULTS: The study showed bone
      conduction threshold elevations ranging in frequency from 9.2 to 14.1 dB in the
      diseased ears. Approximately 39% of the patients had an average difference of
      more than 10 dB for bone conduction, and 12% had an average difference of 20 dB
      or more. Significant relationships were found between threshold elevation and the
      disease type and its duration. Postoperative audiograms showed no significant
      improvement in the bone conduction thresholds in most of the tested patients.
      CONCLUSION: This study suggests that chronic otitis media may result in
      clinically significant bone conduction threshold elevations that should be
      considered when managing uncomplicated chronic suppurative otitis media.

PMID- 9617925
TI  - Pullout strength of adaption screws in thyroid cartilage.
AB  - PURPOSE: To determine the pullout strength of adaption screws in laryngeal
      cartilage and its relationship to drill hole and screw diameter. MATERIALS AND
      METHODS: Screw pullout strength in human cadaver thyroid cartilage was measured
      using a load cell. Screw sizes of 1.3, 1.5, and 2.0 mm were tested using drill
      hole diameters of 0.76, 1.1, and 1.5 mm. RESULTS: Maximum pullout strength was
      achieved using a drill hole diameter of 0.76 mm and a 1.5 mm screw. Pullout
      strength for this combination was 27.5 N. CONCLUSION: Adaption screws can be used
      in thyroid cartilage but pullout strengths will be less than in bone. Drill holes
      for screws in thyroid cartilage should be smaller than those used for cortical
      bone. Maximum strength will be achieved using a 1.5 mm screw in a 0.76 mm drill
      hole.

PMID- 9617926
TI  - The comparative strength of laryngeal fracture fixation.
AB  - PURPOSE: To assess the fixation strength provided by miniplate fixation, wire
      tube batten fixation, and wire fixation alone in repair of thyroid cartilage.
      MATERIALS AND METHODS: Segments 2.5-cm wide x 1-cm long were cut from three
      fresh, frozen, human cadaveric larynges from an 83-year-old man, a 58-year-old
      woman, and an unknown cadaver. A vertical fracture was induced and repaired with
      one of three randomly assigned fixation techniques (n=10 in each fixation group).
      The repaired cartilage was placed in an Instron Universal Testing Device (Boston,
      MA) and subjected to a three-point bending test. Load to failure was recorded on
      an analogue graph. RESULTS: All reconstruction techniques significantly differed
      from each other, with miniplate fixation providing a stronger repair than wire
      tube batten (P < .05), wire tube batten providing a stronger repair than wire
      alone (P < .01), and miniplate providing a stronger repair than wire alone (P <
      .001). CONCLUSION: In experimentally induced fractures of the human larynx,
      miniplate fixation consistently yielded the strongest repair. Although both
      miniplate and wire batten produced excellent anatomic reaction, we feel that
      miniplate fixation was easier to perform.

PMID- 9617927
TI  - Major neck surgeries under regional anesthesia.
AB  - PURPOSE: Major neck surgeries are conventionally performed under general
      anesthesia. To receive general anesthesia, patients must meet certain criteria
      that have attendant limitations. This report discusses the investigator's
      experiences with performing major neck surgeries under regional anesthesia.
      MATERIALS AND METHODS: Fifty major neck surgeries were performed (30
      thyroidectomies, 10 laryngectomies with or without neck dissection, 3
      thyroglossal cyst, 2 branchial cyst, and 5 submandibular gland excisions) under
      regional anesthesia over a period of 2 years between March 1994 and March 1996.
      The selection criteria of patients for regional anesthesia, the regional neural
      blocks used, the technique of performing these blocks, the efficacy, advantages,
      and limitations of these blocks are all discussed. RESULTS: The combination of
      regional neural blocks and intraoperative medications produced superb analgesia
      and good patient compliance. Intraoperative blood loss was minimal. With
      postoperative complications being negligible, recovery was faster. CONCLUSION:
      Regional anesthesia is an effective alternative to general anesthesia for neck
      surgeries of less than 4 hours' duration.

PMID- 9617928
TI  - Acute mastoiditis: a 10-year review.
AB  - PURPOSE: To study how antibiotic treatment and an early decision to aspirate
      subperiosteal abscesses can reduce hospitalization periods and costs in patients
      with acute mastoiditis. PATIENTS AND METHODS: During a 10-year period, 134
      patients were diagnosed with acute mastoiditis at the Department of Ear, Nose,
      and Throat and Head and Neck Surgery (Kaplan Medical Center, Rehovot, Israel).
      The diagnoses was based on physical findings of retroauricular swelling and
      erythema and tenderness, with protrusion of the auricle forward and downward. The
      majority of patients (77) reached medical treatment during the first 3 days of
      their disease. Wide myringotomy and intravenous antibiotic treatment, aspiration,
      and complete cortical mastoidectomy were the treatment options. RESULTS: With the
      administration of wide myringotomy and intravenous antibiotic treatment, 115
      patients recovered; nine received aspiration and did not need surgery; and only
      15 patients who received the antibiotic treatment needed a complete cortical
      mastoidectomy. CONCLUSION: With the wise use of antibiotics and early decision to
      aspirate subperiosteal abscesses, the hospitalization period, the cost, and the
      need for surgery can be reduced.

PMID- 9617929
TI  - Uvulopalatopharyngoplasty: the Naval Medical Center, Portsmouth, experience.
AB  - PURPOSE: To review the surgical results of uvulopalatopharyngoplasties (UPPP)
      performed at the Naval Medical Center, Portsmouth, VA, for the treatment of
      obstructive sleep apnea. The results will be evaluated comparing the recognized
      standard criteria with a proposed revised criteria. MATERIALS AND METHODS: A
      retrospective review was completed of uvulopalatopharyngoplasties performed from
      January 1, 1994 to July 30, 1996. Preoperative polysomnography and apnea-related
      symptoms were compared with those recorded postoperatively. RESULTS: With our new
      proposed criteria, an apnea-hypopnea index of less than 20 and lowest oxygen
      saturation of greater than 85%, the success rate of UPPP was 49%. If patients
      with severe sleep apnea were excluded, the success rate rose to 69%. CONCLUSION:
      UPPP alone is an effective treatment for mild to moderately severe obstructive
      sleep apnea. However, it is not effective as the sole treatment for severe
      obstructive sleep apnea.

PMID- 9617930
TI  - Cartilage reconstruction of the scutum defects in canal wall up mastoidectomies.
AB  - PURPOSE: This study was performed to evaluate whether cartilage reconstruction of
      scutal wall defects diminishes retraction pocket and recurrent cholesteatoma, as
      compared with no cartilage reconstruction of the scutal defect. MATERIALS AND
      METHODS: A retrospective chart review from 1980 to 1993 was performed on all
      patients undergoing a canal wall up mastoidectomy. These procedures were done in
      a large teaching hospital where some surgeons reconstructed with cartilage and
      others did not. The recurrence rate of cholesteatoma and retraction pockets, as
      well as the need for further surgery, was assessed. RESULTS: There were 103 canal
      wall up mastoidectomies performed, and 84 patients were available for long term
      follow-up. Of these, 52 were not reconstructed with cartilage, whereas 32 were
      reconstructed with cartilage. Of the 52 patients not reconstructed, 47% did not
      develop retraction pockets. Of the 53% who did develop a retraction pocket, only
      one third required further surgery, and the others were managed in the office. Of
      the 32 patients that were reconstructed with cartilage, 66% did not develop
      further retractions. Of the 34% who did develop a retraction pocket, one third
      required further surgery. In both groups, those who did require further surgery
      did have recurrent cholesteatoma as well. CONCLUSION: It would appear that
      reconstruction of scutal wall defects after canal wall up mastoidectomies with
      cartilage may be of some benefit in preventing further retraction pockets and
      thus the recurrence of cholesteatoma.

PMID- 9617931
TI  - Frontal sinus surgery: the state of the art.

PMID- 9617932
TI  - Castleman's disease of the retropharynx: a benign tumor in a 12-year-old girl.

PMID- 9617933
TI  - Metastatic follicular thyroid carcinoma to the mandible: a case report and review
      of the literature.

PMID- 9617934
TI  - Extramedullary plasmacytoma of the head and neck.

PMID- 9617935
TI  - Cochlear implantation in a patient with osteogenesis imperfecta and
      otospongiosis.
AB  - PURPOSE: We describe the findings in a patient with osteogenesis imperfecta (van
      der Hoeve syndrome) with otospongiosis who received Nucleus 22-channel (Cochlear
      Pty, Limited, Australia) cochlear implantation. Cochlear implantation in cases of
      osteogenesis imperfecta with otospongiosis appears to be extremely rare. The
      syndrome itself and otospongiosis are both associated with debilitating hearing
      impairment. METHODS: A female patient who had a triad of brittle bones, blue
      sclera, and hearing impairment and underwent cochlear implantation was selected
      for this study. RESULTS: During surgery, otospongiotic feature of hypervascular,
      reddish middle-ear mucosa was found. While performing cochleostomy, very soft and
      brittle cochlear bone was noted, which may be the effect of both osteogenesis
      imperfecta and otospongiosis. CONCLUSION: Although cochlear implantation is not
      always indicated in cases such as described herein, these patients with profound
      deafness may benefit from it.

PMID- 9617936
TI  - Spontaneous dissection of the internal carotid artery presenting with pulsatile
      tinnitus.

PMID- 9617937
TI  - Tumefactive fibroinflammatory lesion of the head and neck originating in the
      infratemporal fossa.

PMID- 9617938
TI  - Tissue engineering: new challenges.

PMID- 9617939
TI  - Daily hemodialysis: history and revival of a superior dialysis method.

PMID- 9617940
TI  - Early years of artificial organs at the Cleveland Clinic: Part II: open heart
      surgery and artificial hearts.

PMID- 9617941
TI  - Push-pull sorbent based pheresis for treatment of acute hepatic failure: the
      BioLogic-detoxifier/plasma filter System.
AB  - The BioLogic-DT (detoxifier) System is an extracorporeal blood treatment device
      that uses the membranes of a cellulosic plate dialyzer to propel blood in and out
      through a single lumen access (on a 12 sec cycle) and circulates a suspension of
      powdered charcoal and cation exchanger through the dialysate spaces to absorb
      many soluble toxins in the treatment of hepatic failure. The BioLogic-DTPF
      (detoxifier/plasma filter) System adds two Gambro plasma filters downstream from
      the plate dialyzer, which allows most of the blood plasma to pass out of the
      blood, contact powdered charcoal in a suspension, and then return to the blood
      during each 12 sec cycle (creating push-pull sorbent based pheresis). A roller
      pump exchanges charcoal suspension between the plasma filter case and a 700 ml
      bag of powdered charcoal suspension. At a blood flow rate of 150-200 ml/min, 100
      ml/min of plasma moves bidirectionally through the plasma filter membranes.
      Direct contact of plasma with charcoal outside the plasma filter membranes
      removes creatinine with a clearance rate equal to plasma flow (100 ml/min);
      clearance of strongly protein bound toxins, such as unconjugated bilirubin, is
      lower (10-40 ml/min). In this article, the authors explain the mechanisms of
      operation of this system and present in vitro tests that define its chemical
      efficiency. Also described are potential problems, tests that indicate the
      severity of these problems, and monitors and algorithms to detect or avoid these
      problems in clinical use of the system. The results of the treatment of two
      patients with acute hepatic failure and coma using the BioLogic-DTPF System are
      reviewed.

PMID- 9617942
TI  - Development of an adjustable prosthesis for the treatment of gastroesophageal
      reflux: preliminary results in a porcine model.
AB  - Dysphagia and recurrent gastroesophageal reflux complicate use of the Angelchik
      prosthesis. The authors developed an inflatable silicone device, similar to the
      Angelchik prosthesis, that may allow for the adjustment of the total pressure
      exerted around the gastroesophageal junction after implantation. To estimate its
      potential to prevent gastroesophageal reflux in humans, we used a short-term
      porcine model in which we measured the effective lower esophageal sphincter
      pressure in 10 anesthetized pigs using a computerized, three dimensional pressure
      vector volume analysis. Anesthesia and mobilization of the gastroesophageal
      junction did not modify the three dimensional pressure vector volume at the lower
      esophageal sphincter. Implantation of the deflated device significantly increased
      effective lower esophageal sphincter three dimensional pressure vector volume
      compared with baseline. Inflation of the device with 30 ml of saline further
      increased lower esophageal sphincter pressure significantly. Deflation of the
      device returned the pressure to the pre-inflation values. Using an animal model
      and short-term implantation, this new antireflux device appeared to offer the
      potential ability to adjust the pressure selectively at the gastroesophageal
      junction postoperatively. An added future feature of this device may be the ease
      of insertion using laparoscopic techniques. Long-term animal implantation studies
      and clinical trials are required to help establish the safety and efficacy of
      this device in humans.

PMID- 9617943
TI  - Modeling of oxygen transport in blood-perfluorocarbon emulsion mixtures: Part I:
      oxygen uptake in tubular vessels.
AB  - Perfluorocarbon (PFC) emulsions are usually used as mixtures with blood to
      enhance its capacity for oxygen, because stand alone PFC emulsions cannot perform
      the normal regulatory functions of blood. These mixtures have been found to be
      very effective in increasing the tissue oxygen tension, especially at high oxygen
      partial pressures, and many experimental observations exist in the literature in
      support of this fact. The explanations for these observations are still
      speculative and unquantified, however. In this work, models have been developed
      to describe oxygen transport in uniform and non-uniform mixtures of blood and
      PFCs. For the latter case, the extreme situation of central migration of
      erythrocytes is considered, wherein the erythrocytes occupy the central core
      region of the vessel surrounded by a plasma annulus. The predictions of the
      proposed models have been examined using a fixed wall oxygen tension, and the
      oxygen transport characteristics of mixtures have been presented with reference
      to blood alone. It was found that at high oxygen tensions the addition of PFCs
      significantly increases the oxygen wall flux into the tube. This increased flux,
      coupled with effects of competing oxygen sinks (erythrocytes and PFC droplets),
      leads to an anomalous increase in the average oxygen tension for short distances
      from the tube entrance. It has been shown that a near wall excess of PFC droplets
      is not necessary to cause this increase, as mentioned by Vaslef and Goldstick.
      For longer distances, however, the addition of PFCs leads to a decrease in the
      average oxygen tension.

PMID- 9617944
TI  - Modeling of oxygen transport in blood-perfluorocarbon emulsion mixtures: Part II:
      tissue oxygenation.
AB  - The models developed in the accompanying article in this issue for oxygen
      transport in uniform (pseudo-homogeneous model) and non-uniform (core annulus
      model) dispersions of erythrocytes and perfluorocarbons (PFCs) have been analyzed
      with a fixed wall flux boundary condition. Such a situation arises in the case of
      oxygen transport from a capillary to the surrounding tissue. The results reveal
      that PFCs are extremely effective in increasing the tissue oxygen tension during
      enriched air breathing. The increased oxygen capacity of blood on the addition of
      PFC emulsion is the main contributor toward this increase. If the contribution of
      the accompanying increase in the arterial oxygen tension also is considered, the
      resulting increase in the tissue oxygen tension was even larger than that
      observed by Braun et al, and hence other factors, such as an increase in the
      cardiac output or service of erythrocyte free capillaries, need not be invoked. A
      near wall excess of PFC droplets, if it occurs, has been shown to have a
      negligible effect on the tissue oxygen tension during normal rates of tissue
      oxygen consumption when the intracapillary gradients are small. In these
      conditions, the capillary phase may be taken to be uniform. A criterion has been
      developed to assess the magnitude of the gradients within the capillary.
      Accordingly, in cases of elevated rates of tissue oxygen consumption or low
      arterial oxygen tensions, the internal gradients become important and the
      capillary phase can no longer be taken to be uniform.

PMID- 9617945
TI  - Hemoglobin based oxygen carrying solution stability in extracorporeal
      circulation: an in vitro evaluation and implications for clinical use.
AB  - This study evaluated the stability of a hemoglobin based oxygen carrying (HBOC)
      solution during extracorporeal circulation. HBOC solution was diluted 1:1 with
      normal saline, 2 L of the resulting solution was oxygenated in either a bubble
      oxygenator (n=5) or membrane oxygenator (n=5), and it was placed in
      extracorporeal circulation at a rate of 2 L/min for 5 hr at 37 degrees C. To
      assess the effect of added human blood, 500 ml of fresh human whole blood was
      added to 1.5 L of diluted HBOC solution, and circulated as described.
      Methemoglobin level, hemoglobin integrity (percent of HBOC solution tetramer),
      and oxygen affinity (PO2 at 50% hemoglobin saturation) were measured.
      Extracorporeal circulation using the bubble oxygenator slightly altered (<1%)
      hemoglobin integrity compared with controls. Oxygen affinity decreased during
      extracorporeal circulation with both the membrane and bubble oxygenators; there
      was no significant difference between the oxygenators. Methemoglobin formation in
      controls and in extracorporeal circulation with either oxygenator was
      significant, with a slight advantage of the membrane compared with the bubble
      oxygenator; however, the presence of blood significantly decreased the rate of
      methemoglobin formation. In the presence of blood, HBOC solution remains
      structurally stable and efficacious for oxygen delivery during extracorporeal
      circulation.

PMID- 9617946
TI  - Evaluation of post extracorporeal membrane oxygenation follow-up testing.
AB  - The purpose of this study was to evaluate all post extracorporeal membrane
      oxygenation (ECMO) tests for their ability to detect any change in the incidence
      of unanticipated medical problems, and their charge to the patient. The current
      post ECMO protocol consists of the following tests: brain stem auditory evoked
      response, head computed tomography, cerebral blood flow, head ultrasonography,
      electroencephalography, eye examination for retinopathy of prematurity, and
      pneumocardiography. A retrospective review was conducted for all surviving
      neonatal ECMO patients treated from January, 1985, to December, 1994. The results
      of each test were classified as either normal, having a minor abnormality, or
      having a major abnormality. Statistical analyses were performed on each test
      comparing the incidence of minor and major abnormalities to all neonates in the
      neonatal intensive care nursery. Two hundred ninety-six infants survived their
      course on ECMO, and composed the study population. There were no significant
      differences between the incidence of abnormal results compared with the expected
      values for the following tests: cerebral blood flow (p=0.13), the eye examination
      (p=0.54), and pneumocardiography (p=0.22). The analyses for the brain stem
      auditory response, head computed tomography, head ultrasonography, and
      electroencephalography showed higher than expected incidences of abnormal results
      (p < 0.01). The data also were evaluated for major abnormalities on computed
      tomography and head ultrasonography. Of 161 infants who had both tests performed,
      11 (6.8%) had normal head ultrasonography results, yet had a major abnormality
      noted on computed tomography (p < 0.01). This study is the first to review the
      current post ECMO protocol comprehensively, and the results suggest excluding the
      cerebral blood flow, eye, and pneumocardiography tests. This would result in a
      significant savings of $1,400 without compromising patient care. In addition,
      comparisons of neuroradiographic studies indicate that computed tomography of the
      head is sensitive enough to detect all central nervous system abnormalities that
      were found by ultrasonography. Excluding the post ECMO head ultrasonography, an
      additional savings of $300 would occur. These recommended changes reflect the
      current post ECMO protocol at Kosair Children's Hospital.

PMID- 9617947
TI  - Complicated cannula insertions and cannula dislodgments associated with
      extracorporeal membrane oxygenation.
AB  - Extracorporeal membrane oxygenation therapy remains a life saving modality for
      neonates with cardiopulmonary disease that is unresponsive to conventional
      therapy. Vital to its success is the insertion and maintenance of appropriately
      sized vascular cannulas. Problematic insertion and accidental dislodgments can be
      life threatening. To determine the treatment and outcome of these complications,
      a survey of participating Extracorporeal Life Support Organization centers was
      undertaken. Venous cannulation complications (13 patients) were due to inadequate
      vein size or tearing during initial attempts at cannulation. Proximal and
      alternative site cannulation were used. Difficult arterial cannulations (seven
      patients) were most often due to creation of an intimal flap that was corrected
      by proximal cannulation of the same vessel. The 10 cases of accidental
      dislodgment were most often associated with changes in position. Despite copious
      hemorrhage in many instances, 6 of 10 patients survived with intact neurologic
      status. Methods for dealing with these life threatening cannula related
      complications are described.

PMID- 9617948
TI  - Tissue engineering of a bioartificial renal tubule.
AB  - Development of a bioartificial renal tubule with a confluent monolayer of renal
      epithelial cells supported on a permeable synthetic surface may be the first step
      to further optimization of renal substitution therapy currently used with
      hemodialysis or hemofiltration. Madin-Darby canine kidney cells, a permanent
      renal epithelial cell line, were seeded into the lumen of single hollow fibers.
      Functional confluence of the cells was demonstrated by the recovery of
      intraluminally perfused 14C-inulin that averaged >98.9% in the cell lined units
      vs <7.4% in the control noncell hollow fibers during identical pressure and flow
      conditions. The baseline absolute fluid transport rate averaged 1.4+/-0.4
      microl/30 min. To test the dependency of fluid flux with oncotic and osmotic
      pressure differences across the bioartificial tubule, albumin was added to the
      extracapillary space, followed by the addition of ouabain, an inhibitor of Na+K+
      adenosine triphosphatase, the enzyme responsible for active transport across the
      renal epithelium. Addition of albumin resulted in a significant increase in
      volume transport to 4.5+/-1.0 microl/30 min. Addition of ouabain inhibited
      transport back to baseline levels of 2.1+/-0.4 microl/30 min. These results are
      the first demonstration that renal epithelial cells have been grown successfully
      as a confluent monolayer along a hollow fiber, and exhibit functional transport
      capabilities. The next steps in constructing a bioartificial renal tubule
      successfully are to develop a multi-fiber bioreactor with primary renal proximal
      tubule cells that maintain not only transport properties but also differentiated
      metabolic and endocrine functions, including glucose and ammonia production, and
      the conversion of vitamin D3 to a more active derivative. A renal tubule device
      may add critical renal functional components not currently substituted for,
      thereby improving the treatment regimens for patients with acute and chronic
      renal failure.

PMID- 9617949
TI  - On-line dialysis quantification in acutely ill patients: preliminary clinical
      experience with a multipurpose urea sensor monitoring device.
AB  - Direct dialysis quantification offers several advantages compared with
      conventional blood urea kinetic modeling, and monitoring urea concentration in
      the effluent dialysate with an on-line urea sensor is a practical approach. Such
      a monitoring device seems desirable in the short-term dialysis setting to
      optimize and personalize both renal replacement therapy and nutritional support
      of acutely ill patients. We designed a urea monitoring device consisting of a
      urea sensor, a multichannel hydraulic circuit, and a PC microcomputer. The sensor
      determines urea from catalysis of its hydrolysis by urease in liquid solution
      during neutral conditions. Hydrolysis of urea produces NH4+, and creates an
      electrical potential difference between two electrodes. Each concentration
      determination of urea is the average value of 10 measurements; samples are
      diverted and measured every 7 min. Laboratory calibration of the urea sensor has
      demonstrated linearity over the range 2-35 mmol/L. Urea monitoring was performed
      throughout the treatment course, either on the effluent dialysate or
      ultrafiltrate in seven acutely ill patients treated by either hemofiltration
      (n=5) or hemodiafiltration (n=2). The slope of the concentration of urea in the
      effluent over time was used to calculate an index of the dialysis dose delivered
      (Kt/V), urea mass removal, and protein catabolic rate. In addition, samples of
      the effluent were drawn every 21 min, and sent to the central laboratory for
      measurement of urea concentrations using an autoanalyzer. Kt/V values also were
      calculated with Garred's equation using pre and post session concentrations of
      urea in blood. Concentrations of urea in the effluent determined by the urea
      sensor were found to be very close to those obtained from the central laboratory
      over a wide range of values (3 to 42 mmol/L). In addition, Kt/V values for both
      hemofiltration and hemodiafiltration, when calculated with concentrations of urea
      in the effluent obtained by the urea sensor, did not significantly differ from
      Kt/V values obtained from the laboratory concentrations of urea in the effluent.
      On-line urea sensor monitoring of the effluent suppresses the cumbersome task of
      total effluent collection, and the complexity of urea kinetic analysis. The
      multipurpose prototype described here represents a new, simple, and direct
      assessment of dialysis dose and protein nutritional status of acutely ill
      patients, and is suitable for various modalities.

PMID- 9617950
TI  - A comparison of methods for the measurement of hemodialysis access recirculation:
      an update.
AB  - The Crit-Line Model III (CRIT) was compared with the Transonics Hemodialysis
      Monitor (TRANS) with regard to its ability to measure access recirculation (AR).
      Patients were studied during routine dialysis before and after dialysis line
      reversal done to induce AR. A strong correlation between CRIT and TRANS AR
      measurements was obtained (r=0.95; p=0.000; n=58) and CRIT values were repeatable
      (normalized SD from mean 7.82%). The CRIT values were not identical to TRANS; at
      low AR values (< 20%) they overestimated, and at higher values they
      underestimated. Provided this is appreciated, CRIT AR values are clinically
      useful.

PMID- 9617951
TI  - Twenty-one year mortality in a dialysis unit: changing effect of withdrawal from
      dialysis.
AB  - To characterize the factors affecting the decision to withdraw from dialysis, the
      authors compared patients withdrawing from dialysis (n=62) with patients dying
      from all other causes (n=242) over 21 years (1976-1996) in a single dialysis
      unit. Compared with those who died from other causes, patients who withdrew were
      older (67+/-11 vs 61+/-11 years); were more likely to have severe physical
      impairment (87% vs 62%) and severe restriction of activities of daily living (77%
      vs 46%); and had higher frequencies of congestive heart failure (81 % vs 62%),
      myocardial infarction (60% vs 42%), peripheral vascular disease (71 % vs 40%),
      and diabetes mellitus (66% vs 36%) (p < or = 0.014). Dialysis modality; duration
      of dialysis; the degree of family support; index of disease severity; the use of
      tobacco, alcohol, or illicit drugs; and the frequency of ischemic heart disease,
      dysrhythmia, pericarditis, cardiac arrest, cerebrovascular accident,
      hypertension, obstructive lung disease, cancer, and human immunodeficiency virus
      did not differ between the two groups. Stepwise logistic regression showed that
      dialysis during 1990-1996, severe limitation of activities of daily living, and
      diabetes mellitus were independent risk factors for withdrawal. During 1990-1996,
      44% of the deaths were caused by withdrawal from treatment. In addition to other
      factors, dialysis in the 1990s is a strong predictor of withdrawal from dialysis.
      The reasons for the increased rate of withdrawal from dialysis in recent years,
      and the effect of this increased rate of withdrawal on mortality, need further
      evaluation.

PMID- 9617952
TI  - Comparison of the in vivo behavior of polyvinylidene fluoride and polypropylene
      sutures used in vascular surgery.
AB  - To find a nonabsorbable suture material that is equivalent to polypropylene in
      ease of handling and tensile properties, and that has low thrombogenicity and
      tissue reactivity but improved biostability, some researchers and clinicians see
      merit in considering the suitability of monofilaments made from polyvinylidene
      fluoride. The current animal study investigated the relative biocompatibility and
      biostability of these two suture materials by using them to anastomose a
      polyester arterial prosthesis in a canine thoracoabdominal bypass model for 10
      periods of implantation ranging from 4 hr to 2 years. Biocompatibility was
      assessed with light and scanning electron microscope examinations of the
      explanted sutures, and biostability of the cleaned sutures was determined by
      Fourier transform infrared spectroscopy and scanning electron microscope
      analysis. The polyvinylidene fluoride and polypropylene sutures were found to
      have similar handling and healing characteristics. During the first months in
      vivo, both types of suture experienced a temporary increase in carbonyl group
      absorption that coincided with the duration of the inflammatory response. After 1
      and 2 years in vivo, the explanted polypropylene sutures showed visual evidence
      of surface stress cracking. This was not found with the explanted polyvinylidene
      fluoride sutures. These results suggest that polyvinylidene fluoride may be more
      biostable than polypropylene in the long term.

PMID- 9617953
TI  - Current progress in the development of a totally implantable Gyro centrifugal
      artificial heart.
AB  - A totally implantable centrifugal artificial heart has been developed using a
      miniaturized pivot bearing supported centrifugal pump (Gyro PI pump). The authors
      report current progress in its development. The Gyro PI-601 has a priming volume
      of 20 ml, weighs 100 g, has a height of 60 mm, and has a diameter of 65 mm. This
      pump can provide 8 L/min against 150 mmHg at 2,250 rpm. It is driven by an
      miniaturized DC brushless motor with the coils fixed in a plastic mold that is
      waterproof and made of titanium (weight, 204 g; height, 18 mm; diameter, 65 mm).
      In this centrifugal artificial heart, two Gyro PI pumps are implanted
      independently to replace cardiac function without resecting the native heart. Its
      anatomic and surgical feasibility were confirmed experimentally. The Gyro PI-601
      was implanted as a right or left ventricular assist device in the preperitoneal
      space of five calves. All five tests proceeded without any thromboembolic
      symptoms. One of five tests was extended more than 1 month to confirm the long
      term feasibility of the Gyro PI-601 pump system. Based on the satisfactory
      results of the in vivo tests, the material conversion of the Gyro PI from
      polycarbonate to titanium alloy (Ti-6A1-4V) was undertaken to improve its
      biocompatibility for long-term implantation.

PMID- 9617954
TI  - Tumor necrosis factor-alpha in plasma during cardiopulmonary bypass in a pig
      model: correlation with marginated neutrophils and cerebral edema by magnetic
      resonance imaging.
AB  - Tumor necrosis factor (TNFalpha) initiates the cytokine cascade via the nuclear
      factor (NFkappaB), increasing vascular permeability, inflammation, and edema
      during and after cardiopulmonary bypass (CPB). Cerebral edema before and after
      thoracotomy and CPB was evaluated by magnetic resonance imaging. TNF-alpha in
      plasma was measured in 12 Yorkshire pigs with an enzyme linked immunosorbent
      assay technique using a monoclonal antibody made against porcine TNFalpha. Blood
      samples were taken 30 min before and 1, 30, 60, 90, 120, 150, and 180 min after
      initiation of CPB. Plasma was separated from packed cells after centrifugation,
      and frozen at -80 degrees C. The level of TNFalpha, measured by color intensity,
      was read with a 96 well microtiter plate reader. Normal values in plasma were low
      (range, 0-17 pg/ml; mean, 4.7 pg/ml). In sham control pigs undergoing sternotomy,
      and pigs that had undergone CBP, TNFalpha reached a peak value at 120-150 min,
      and subsequently declined. TNFalpha in plasma increased in pigs that underwent
      thoracotomy and CPB. The increase was significantly higher in pigs that underwent
      CPB. Neutrophil mapping in the pig brain with 111In-labeled autologous
      neutrophils 180 min after CPB, suggested almost uniform distribution and
      accounted for the 0.02% of total circulating neutrophils in the brain,
      corresponding to a total of 8 x 10(5) neutrophils. Magnetic resonance imaging of
      the pig brain indicated the presence of cerebral edema after CPB, as depicted by
      the loss of structural details of the sulci, gyri, and ventricles. Activated
      neutrophils, monocytes, and other inflammatory cells may induce multi-organ edema
      and injury via TNFalpha and other regional cytokines.

PMID- 9617955
TI  - Severe acute extrinsic airway compression by mediastinal tumor successfully
      managed with extracorporeal membrane oxygenation.
AB  - The successful use of femoral venoarterial extracorporeal membrane oxygenation to
      support an adult patient with extrinsic airway compression secondary to a large
      mediastinal tumor is presented. Extracorporeal membrane oxygenation was continued
      until a combination of chemotherapy and radiation therapy allowed sufficient
      tumor shrinkage to permit decannulation. This method should be considered and
      available before manipulation of the airway in similar patients.

PMID- 9617956
TI  - Advances in the management of respiratory failure: overview.

PMID- 9617957
TI  - Arteriovenous carbon dioxide removal.

PMID- 9617958
TI  - Intracorporeal gas exchange: taking further steps.

PMID- 9617959
TI  - Current status of inhaled nitric oxide in respiratory failure.

PMID- 9617960
TI  - Concepts in ventilator strategies.

PMID- 9617961
TI  - Liquid ventilation in the setting of respiratory failure.

PMID- 9617962
TI  - Rotary pumps: new developments and future perspectives.

PMID- 9617963
TI  - Mitral regurgitation of the On-X size 23 valve is comparable to or less than the
      size 27 SJM, which has the same geometric orifice area.

PMID- 9617964
TI  - Laparoscopic surgery and splanchnic vessel thrombosis.
AB  - We report a case of fatal mesenteric artery thrombosis following laparoscopic
      cholecystectomy in a 60-year-old hypertensive woman, whose preoperative
      complaints were not typical of calculous biliary disease. Two previous case
      reports have associated laparoscopic cholecystectomy and acute intestinal
      ischemia; one of these patients died. Experimental and clinical data indicate
      that carbon dioxide pneumoperitoneum reduces splanchnic blood flow through
      several mechanical and physiologic mechanisms. Consequently, we believe that,
      when laparoscopic surgery is contemplated, physicians and patients should be
      aware of the risk of splanchnic vessel thrombosis, especially when certain pre
      existing conditions are present (e.g., impairment of splanchnic vessel flow,
      hypercoagulable states, etc.). For such high-risk patients, especially when the
      planned laparoscopic procedure may be lengthy, gasless or low-pressure
      laparoscopic surgery, or even reversion to traditional open surgery should be
      considered.

PMID- 9617965
TI  - Robotically assisted laparoscopic tubal anastomosis in a porcine model: a pilot
      study.
AB  - As with standard microsurgical procedures performed at laparotomy, laparoscopic
      tubal anastomosis requires great dexterity. Handling fine suture materials under
      magnification to anastomose tubal segments with lumens less than 3 mm in diameter
      while working with your hands at a distance from the tissue makes these fine
      movements even more difficult. This is exacerbated by the tremor induced by the
      fatigue caused by a prolonged laparoscopic procedure and the need for precise
      control. We conducted a pilot study to evaluate the feasibility of performing
      laparoscopic tubal anastomosis with robotic assistance in a live porcine model.
      Two anastomoses were performed on one uterine horn via each of the following
      techniques: laparoscopy, laparoscopy with robotic assistance, and open
      microsurgery. Immediate necropsy demonstrated all the anastomoses to be patent.
      There were no intraoperative complications. Laparoscopic tubal anastomosis was
      associated with surgeon fatigue and neck, shoulder, and back pain. The surgeons
      were more comfortable performing the procedure with robotic assistance. The
      device functioned well and without incident. This acute animal study suggests
      that robotic assistance in laparoscopic tubal anastomoses is safe and feasible.
      It enhances surgeons' dexterity and precision while reducing fatigue. It is
      promising for future use in chronic experimental studies.

PMID- 9617966
TI  - A laparoscopic approach to posterior gastric wall leiomyomectomy.
AB  - Leiomyomas represent 2% of gastric tumors. Commonly, gastric leiomyomas are
      clinically silent. Most often they become clinically apparent due to bleeding
      from ulceration of the overlying gastric mucosa. Surgical extirpation of the
      tumor is the standard treatment. Gastric leiomyomectomy was done routinely
      through open laparotomy until availability of laparoscopic equipment and
      techniques. Recently, there have been a few published reports regarding
      laparoscopic or laparoscopic-assisted removal of smooth muscle gastric tumors.
      There is little data, however, describing or discussing a laparoscopic approach
      to gastric leiomyomas located on the posterior gastric wall. We describe two
      different laparoscopic approaches to posterior wall gastric leiomyomas that we
      used in two patients. The postoperative recovery of both patients was remarkably
      quick and uneventful.

PMID- 9617967
TI  - Simplified technique for unrolling prosthetic mesh during laparoscopic ventral
      hernia repair.
AB  - Laparoscopic ventral herniorraphy is an attractive alternative to conventional
      open repair. It preserves the benefits of minimally invasive surgical procedures
      by offering decreased discomfort and hospital stay while affording a low
      recurrence rate. Although technically feasible, unrolling a large piece of
      prosthetic mesh within the peritoneal cavity is often time consuming and the most
      frustrating step in the procedure. Our group describes a simplified technique for
      unrolling mesh that is quick, easy to perform, and requires no specialized
      equipment.

PMID- 9617968
TI  - Effects of various laser wavelengths and energy levels on pig rectal submucosal
      tissue.
AB  - This phase I animal study attempts to develop a nonexcisional method of treating
      hemorrhoidal varicosities submucosally using interstitial laser beam. Three laser
      wavelengths at four energy levels were applied interstitially to pig rectal
      submucosa to evaluate the effects on the vasculature, mucosa, and the muscle. As
      expected YAG laser caused a "cooking" of the tissue with necrosis and abscess
      formation. KTP laser was intermediate in its effect, causing less mucosal injury
      and muscle necrosis. Pulse dye laser had more specific effects on the vessels
      with little damage to the mucosa or muscle layers. Further studies using pulse
      laser are warranted as a possible nonexcisional interstitial treatment for
      hemorrhoids.

PMID- 9617969
TI  - Retroperitoneal abscess as a complication of retained gallstones following
      laparoscopic cholecystectomy.
AB  - Retroperitoneal abscess formation secondary to retained spilled gallstones after
      laparoscopic cholecystectomy is a rare complication. We describe the case of a
      patient with this complication as well as a novel method utilizing interventional
      radiologic localization with subsequent operative drainage and removal of the
      stones. A review of the literature is provided.

PMID- 9617970
TI  - Laparoscopy to correctly diagnose and treat Crohn's disease of the ileum.
AB  - A 27-year-old woman with a past history of pulmonary tuberculosis presented with
      right iliac fossa pain and low-grade fever. She was empirically treated for
      Crohn's disease despite undergoing multiple investigations that failed to provide
      a strongly suspected diagnosis. After 3 days of therapy, her symptomatology
      aggravated, and signs suggestive of intestinal obstruction developed. Placing the
      patient in the left lateral decubitus position before sterile draping,
      intracorporeal laparoscopy was performed, and Crohn's disease involving the
      terminal ileum but sparing its most distal 25 cm was confirmed. During the
      procedure, creeping mesenteric fat, a characteristic feature of Crohn's disease,
      was seen. Also, some adhesions in the right iliac fossa and a firm 3-cm
      inflammatory mass were found. Both division of mesentery along with terminal
      ileum resection and ileocolonic anastomosis were successfully performed
      intracorporeally, without need to convert to open surgery. In select cases of
      right iliac fossa pain in which diagnostic and therapeutic results are
      inconclusive or equivocal, laparoscopy can be useful to correctly diagnose and
      treat inflammatory bowel disorders such as Crohn's disease. Moreover, we suggest
      that intracorporeal laparoscopic surgery can be effective in the treatment of
      these conditions even in some cases with intestinal complications such as
      inflammatory masses and adhesions.

PMID- 9617971
TI  - Should uterine size alone require laparoscopic assistance? Vaginal hysterectomy
      for a 2003-g uterus.
AB  - The main determinants of suitability for vaginal hysterectomy for benign uterine
      pathology in the medically stable patient are uterine mobility and adequate
      vaginal exposure. The removal of a 2,003-g fibroid uterus by total vaginal
      hysterectomy by morcellation in a woman suffering from severe menometrorraghia is
      reported.

PMID- 9617972
TI  - Morgagni's hernia resolved by laparoscopic surgery.
AB  - Morgagni's hernias represent between 2 and 4% of the whole of nontraumatic
      diaphragmatic hernias in the adult, and the treatment (even with minimal
      symptoms) is always with surgery. We present the case of a 50-year-old woman with
      an oppressive, postprandial discomfort in the right side of her thorax and with
      increased pain when supine. The x-ray examination indicated a large portion of
      transverse colon inside the thoracic cavity. Once the diagnosis of Morgagni's
      hernia had been obtained, she was scheduled for laparoscopic surgery to reduce
      the hernia and to reconstruct the defect of the diaphragm using a polypropylene
      mesh.

PMID- 9617973
TI  - Untoward cardiac changes during CO2 insufflation in laparoscopic
      cholecystectomies in low-risk patients.
AB  - In the past decade, laparoscopic cholecystectomy has become the gold standard
      treatment for gallbladder disease. A debate has arisen about using CO2 to distend
      the abdomen because of negative effects on venous return to the heart and
      declining cardiac output. Some authors have supported the use of pulmonary artery
      catheters for intraoperative monitoring while others have recommended gasless
      techniques to avoid these negative effects for high-risk patients. In this study,
      four cases of bradycardia and/or asystole during CO2 pneumoinsufflation at the
      beginning of planned, elective laparoscopic cholecystectomies are described.
      These patients were ASA category II, without history of cardiac disease. To
      determine the frequency and any underlying common denominators, we analyzed these
      laparoscopic cholecystectomies. Each patient experienced bradycardia shortly
      after the start of the laparoscopic cholecystectomy. None had known cardiac
      disease or symptoms. Two were on antihypertensive medications, and one had
      experienced an episode of unexplained bradycardia 6 years earlier. These cases
      occurred during 725 laparoscopic cholecystectomies (0.6% approximately). Using
      the senior author's conversion rate of 10% to open cholecystectomies, the entire
      group would be approximately 800, and the risk of bradycardia upon induction of
      CO2 is 4 per 800, or 0.5%. Although cardiovascular changes were noted during
      laparoscopic gynecologic surgery approximately 20 years ago, only in the last few
      years have cardiovascular changes been reported during laparoscopic
      cholecystectomies. This study reviews four cases of bradycardia during CO2
      insufflation in patients that were considered to be low-risk. Surgeons should be
      prepared to encounter such cardiovascular changes even with low-risk patients.

PMID- 9617974
TI  - Needlescopic cholecystectomies.

PMID- 9617975
TI  - Conflicts of interest, redundant publication, and identification of authorship: a
      plea for trust instead of suspicion.

PMID- 9617976
TI  - Clinical characteristics of response to fluoxetine treatment of obsessive
      compulsive disorder.
AB  - Fluoxetine is effective in treating obsessive-compulsive disorder (OCD).
      Nonetheless, a substantial number of patients do not respond or have only partial
      improvement. Data generated by a multicenter, placebo-controlled, fixed-dose
      trial of fluoxetine were reanalyzed to identify characteristics of responders.
      Multiple regression methods were used to evaluate the relationship between
      therapeutic response and baseline measures such as severity of symptoms, type of
      symptoms (obsessions, compulsions, depression), course of illness, previous
      treatment, age of onset, and other demographic factors (age, race, and sex).
      Fluoxetine was more effective than placebo on all outcome measures. A 60-mg
      dosage was associated with a greater drop in Yale-Brown Obsessive-Compulsive
      Scale total score and a greater drop in Compulsion items than a 20-mg dosage.
      Response rates and overall improvement were greatest for patients with a history
      of remissions, with no previous drug treatment or with only prior behavior
      therapy, with more severe OCD (especially with greater interference and distress
      from obsessions), or with either low or high Hamilton Rating Scale for Depression
      scores. This study did not detect any associations between response and current
      age, age of OCD onset, gender, and race. None of the demographic or clinical
      factors evaluated was found to be related to improvement in the placebo group.

PMID- 9617977
TI  - Safety of abrupt discontinuation of fluoxetine: a randomized, placebo-controlled
      study.
AB  - Selective serotonin reuptake inhibitors may be associated with new adverse events
      after abrupt discontinuation. Hypothesizing that the long half-life of fluoxetine
      would be protective, this study analyzed the effects of abrupt fluoxetine
      discontinuation during a randomized, double-blind, placebo-controlled study of
      depression maintenance treatment. After 12 weeks of fluoxetine treatment (20
      mg/day), 395 responders were abruptly randomized to placebo (N = 96) or to
      continued fluoxetine (N = 299). Patients were seen at weeks 1, 2, 4, and 6 after
      randomization. Reports of new or worsened adverse events were similar for both
      groups at each visit after randomization. Patient discontinuations related to
      adverse events were also similar in both groups. Mild, self-limited
      lightheadedness or dizziness occurred in a small percentage of patients who
      discontinued fluoxetine treatment but was of little clinical significance. No
      cluster of symptoms suggestive of a discontinuation syndrome was observed. Abrupt
      discontinuation of fluoxetine treatment was well tolerated and did not seem to be
      associated with significant clinical risk. Fluoxetine may offer a potential
      safety advantage over shorter-acting agents with respect to treatment
      interruption and/or discontinuation and may be a better choice for those patients
      who are likely to miss doses because of travel or forgetfulness.

PMID- 9617978
TI  - Determinants of interindividual variability and extent of CYP2D6 and CYP1A2
      inhibition by paroxetine and fluvoxamine in vivo.
AB  - Major depression may require antidepressant treatment for several years. This
      necessitates consideration of the long-term effects of antidepressants on
      multiple clinical endpoints. The antidepressants paroxetine and fluvoxamine are
      potent in vitro inhibitors of CYP2D6 and CYP1A2 isozymes, respectively. CYP2D6
      and CYP1A2 are important for the clearance of 30 or more frequently used
      medications. Moreover, CYP1A2 also contributes to metabolism of 17beta-estradiol
      and metabolic activation of environmental procarcinogens (e.g., arylamines in
      cigarette smoke). The aim of this study was to assess the determinants of
      interindividual variability and extent of CYP2D6 and CYP1A2 inhibition during
      paroxetine and fluvoxamine treatment. Healthy volunteers and patients received
      caffeine (100 mg) and dextromethorphan (30 mg) at baseline and at steady state of
      paroxetine (10-20 mg/day, 5-74 days, N = 13) or fluvoxamine (50-100 mg/day, 5-43
      days, N = 8). The caffeine metabolic ratio (CMR) and the log O-demethylation
      ratio (ODMR) of dextromethorphan in overnight urine were used as in vivo indices
      of the CYP1A2 and CYP2D6 isozyme activities, respectively. All subjects had an
      extensive metabolizer phenotype for CYP2D6. After fluvoxamine treatment, baseline
      CMR 5.1 +/- 1.4 (mean +/- SD) decreased to 2.7 +/- 1.1 (p < 0.01). Paroxetine did
      not have a significant effect on CMR (p > 0.05). In seven of eight subjects in
      the fluvoxamine group, posttreatment CMR was comparable with the minimum CMR
      value (2.0) attainable in nonsmoking healthy volunteers. After paroxetine
      treatment, log ODMR changed from a baseline value of -2.28 +/- 0.37 to -1.13 +/-
      0.44, indicating significant inhibition of CYP2D6 (p < 0.001). Subjects' CYP2D6
      phenotype did not change after paroxetine treatment. Fluvoxamine had no
      significant effect on log ODMR (p > 0.05). The extent of inhibition of CYP2D6 and
      CYP1A2 by paroxetine and fluvoxamine, respectively, displayed a positive
      correlation with baseline enzyme activity (p < 0.05). In addition, a negative
      association was found between the plasma paroxetine concentration and the CYP2D6
      activity after paroxetine treatment (r = -0.47, p < 0.05). These data indicate
      that paroxetine and fluvoxamine treatment with minimum clinically effective doses
      significantly inhibit CYP2D6 and CYP1A2, respectively. The extent of inhibition
      of CYP2D6 by paroxetine and of CYP1A2 by fluvoxamine is dependent in part on the
      baseline enzyme activity. The interindividual variability in CYP2D6 inhibition by
      paroxetine can also be explained by variability in plasma paroxetine
      concentration. Most patients treated with fluvoxamine (50-100 mg/day) will reach
      population minimums for CYP1A2 activity. These results have potential
      implications for interindividual variability in the risk for drug-drug
      interactions mediated by CYP2D6 and CYP1A2 as well as for the disposition of
      17beta-estradiol and environmental procarcinogens.

PMID- 9617979
TI  - Augmentation with fluvoxamine but not maprotiline improves negative symptoms in
      treated schizophrenia: evidence for a specific serotonergic effect from a double
      blind study.
AB  - There is considerable evidence that adding selective serotonin reuptake inhibitor
      (SSRI) antidepressants to antipsychotic treatment improves negative symptoms of
      schizophrenia. This augmentation effect may be due to "nonspecific"
      antidepressant action or be specifically related to action on the serotonergic
      system. This study examined the serotonergic specificity of SSRI augmentation by
      comparing an SSRI antidepressant with a comparably effective antidepressant
      acting via the noradrenergic system. Consenting patients having chronic
      schizophrenia with prominent negative symptoms were studied. Either fluvoxamine
      or maprotiline was added to their regular antipsychotic treatment in a double
      blind manner for 6 weeks. Patients were assessed using the Brief Psychiatric
      Rating Scale, the Scale for the Assessment of Negative Symptoms, the Scale for
      the Assessment of Positive Symptoms, the Montgomery-Asberg Depression Rating
      Scale (MADRS), and the Neurological Rating Scale for Extrapyramidal Side Effects.
      Twenty-five patients completed the study. Negative symptoms improved
      significantly in the fluvoxamine group, but not in the maprotiline group. MADRS
      scores, which were low, did not change significantly in either group. Positive
      symptoms were not affected by either treatment. It is concluded that the
      mechanism by which fluvoxamine augmentation improves negative symptoms involves
      the serotonergic system and is distinct from its antidepressant action.

PMID- 9617980
TI  - Venlafaxine's effects on healthy volunteers' driving, psychomotor, and vigilance
      performance during 15-day fixed and incremental dosing regimens.
AB  - Effects of venlafaxine, an antidepressant acting by selective serotonin and
      norepinephrine reuptake inhibition with a potency ratio of 5:1, were assessed in
      a standardized, actual driving test, a battery of psychomotor tests (Critical
      Flicker/Fusion Frequency, Critical Tracking, Divided Attention), and a 45-minute
      vigilance test (Mackworth Clock). Thirty-seven healthy volunteers, 22 of whom
      completed the study, received venlafaxine in fixed (37.5 mg twice a day) and
      incremental (37.5-75 mg twice a day) doses as well as mianserin (10-20 mg three
      times a day) and placebo according to a 4-period (15 days each), double-blind,
      crossover design. Testing occurred on days 1 and 7 and after dose increments, on
      days 8 and 15. Plasma concentrations of venlafaxine and its active metabolite
      were measured on test days for confirming compliance. Venlafaxine had no
      significant effect on the primary driving parameter (standard deviation of
      lateral position) and failed to impair psychomotor performance. Mianserin
      profoundly and consistently impaired driving and psychomotor performance.
      However, both drugs significantly impaired vigilance performance. Maximal effects
      occurred on day 1 with mianserin and similarly on day 7 with venlafaxine in both
      series. The increment in venlafaxine's dose on day 8 did not increase this
      effect. The drug's selectively impairing effect on vigilance is shared by other
      "serotonergic" anxiolytics and antidepressants, suggesting that interference with
      5-HT transmission reduces arousal in particularly monotonous tasks or
      environments. This study concludes that venlafaxine does not generally affect
      driving ability and should be safe for use by patients who drive.

PMID- 9617981
TI  - Relationship between blood serotonergic variables, melancholic traits, and
      response to antidepressant treatments.
AB  - The relationship between peripheral serotonergic variables, melancholic traits,
      and clinical improvement after antidepressant treatment was examined in 83 drug
      free major depressive patients. Plasma serotonin (5-HT) concentrations was lower
      in untreated melancholic patients (1.00 +/- 0.11 vs. 1.84 +/- 0.28 ng/mL, p <
      0.008; N = 40 and 43, respectively). A tendency was observed for plasma 5
      hydroxyindoleacetic acid (p < 0.06), whereas platelet 5-HT and plasma tryptophan
      did not differ between groups. After blood sampling and clinical ratings,
      treatment began with fixed doses of 5-HT uptake inhibitors (clomipramine or
      fluvoxamine), monoamine oxidase inhibitors, or tianeptine, a 5-HT uptake
      enhancer. There was no significant difference in response rates between patients
      with and without melancholic traits. The relationship between the clinical
      response at 6 weeks (>50% reduction of baseline Hamilton score) and the
      pretreatment values of biochemical variables was examined. Responders had a lower
      pretreatment platelet 5-HT (530 +/- 36 vs. 664 +/- 50 ng/10(9) platelets, p <
      0.03; N = 44 and 39, respectively). Patients with a platelet 5-HT concentration
      above 800 ng/10(9) platelets had a lower response rate than those below this
      value (p < 0.003). This difference was maximal in the subgroup of patients
      treated with 5-HT uptake inhibitors (N = 49). In this subgroup, the response
      rates of patients with 5-HT concentrations below and above the cutoff point were,
      respectively, 70% and 17% (p < 0.001). A pretreatment platelet 5-HT value above
      800 ng/10(9) platelets had a predictive value for a negative response of 92%.
      These results suggest the presence of biochemical differences in the peripheral
      serotonergic system between melancholic and nonmelancholic patients. The inverse
      relationship between the pretreatment platelet 5-HT content and clinical response
      may be useful in the investigation of the relationship between the 5-HT system
      and antidepressant response.

PMID- 9617982
TI  - Sibutramine: a new weight loss agent without evidence of the abuse potential
      associated with amphetamines.
AB  - Sibutramine is a serotonin and norepinephrine reuptake inhibitor that has shown
      efficacy as a weight loss and weight maintenance agent. Because of the abuse
      liability and physical dependence potential of amphetamines and related
      antiobesity agents, this study evaluated the abuse potential of sibutramine and
      compared it with that of dextroamphetamine and placebo in recreational stimulant
      users. Thirty-one male recreational stimulant users participated in this single
      site, Latin square crossover study that compared the effects of two doses of
      sibutramine (20 mg and 30 mg) to dextroamphetamine (20 mg and 30 mg) and placebo,
      using a series of validated subjective scales or questionnaires. For scales
      measuring stimulation and euphoria, there was a greater mean response for
      dextroamphetamine 30 mg versus 20 mg, with both doses having a significantly
      greater stimulant and euphoric effect than placebo at the majority of time points
      (p < 0.05); responses for both doses of sibutramine were statistically
      indistinguishable from placebo at all time points. Responses to "street value"
      and "most enjoyed study session" questions confirmed that sibutramine lacks abuse
      potential; mean cash value estimates of street value were significantly greater
      for both dextroamphetamine doses than for placebo or either sibutramine doses (p
      < 0.05), and the rank order of session enjoyment placed both doses of sibutramine
      last. Together with the relatively late Tmax of the active metabolites (3-4
      hours), this short-term, single-dose study provides strong evidence that
      sibutramine does not have the potential for abuse that is characteristic of
      amphetamines and that it is indistinguishable from placebo in abuse potential.

PMID- 9617983
TI  - Effect of over-the-counter dosages of naproxen sodium and acetaminophen on plasma
      lithium concentrations in normal volunteers.
AB  - Prescription doses of nonsteroidal antiinflammatory agents have been shown to
      decrease clearance and increase plasma concentrations of lithium. This study was
      designed to evaluate whether over-the-counter (OTC) doses of naproxen sodium or
      acetaminophen have the same potential to affect lithium concentration. This was a
      prospective, crossover, 3-phase study conducted at the Clinical Pharmacology
      Studies Unit of the Albany Medical Center Hospital during July and August of
      1995. The 3-phase study comprised the following: phase 1, lithium carbonate (300
      mg every 12 hours) alone for 7 days; phase 2, lithium and either naproxen sodium
      (220 mg every 8 hours) or acetaminophen (650 mg every 6 hours) for 5 days; and
      phase 3, a 2-day washout period followed by a crossover to lithium with the
      alternate drug (acetaminophen or naproxen sodium) for 5 days. Twelve healthy male
      volunteers were recruited, nine of whom completed the study and were included in
      the statistical analysis. Mean (+/-SD) plasma lithium concentrations for subjects
      in treatment group 1 (lithium in phase 1, lithium and naproxen sodium in phase 2,
      lithium and acetaminophen in phase 3) were 0.38 (+/-0.11), 0.40 (+/-0.07), and
      0.36 (+/-0.11) mEq/L, respectively. Mean plasma lithium concentrations for
      subjects in treatment group 2 (lithium in phase 1, lithium and acetaminophen in
      phase 2, lithium and naproxen sodium in phase 3) were 0.43 (+/-0.05), 0.48 (+/
      0.10), and 0.48 (+/-0.05) mEq/L, respectively. One-way repeated-measures analysis
      of variance and paired t-test showed no statistically significant differences
      (p>0.05) in plasma lithium concentrations during any phase of the study. The
      results of this study demonstrated that OTC doses of naproxen sodium and
      acetaminophen did not increase plasma lithium concentrations in these volunteers
      when taken for short periods of time.

PMID- 9617984
TI  - Enhanced selective attention after low-dose administration of the benzodiazepine
      antagonist flumazenil.
AB  - Although recognized for their sedative properties, benzodiazepines are also known
      to impair sustained and selective attention. Flumazenil at low doses may act to
      antagonize benzodiazepine-induced effects. This study examined whether low doses
      of flumazenil would improve event-related brain potential (ERP) indicators of
      selective attention and induce feelings of activation and anxiety in healthy men.
      Data from 11 men (24-30 years) who received intravenous flumazenil (0.2 mg, plus
      0.3 mg 30 minutes later) and placebo were analyzed according to a double-blind
      crossover design. ERPs were recorded while subjects performed an auditory
      selective attention task. Mismatch negativity (MMN), processing negativity (PN),
      and the P3 component were extracted from the ERP as markers of preattentive
      mismatch processing, selective attention, and stimulus processing within working
      memory, respectively. Counting accuracy and performance on a letter cancellation
      test were used as behavioral indicators of attention. Mood was assessed by an
      adjective checklist and the State-Trait Anxiety Inventory. Flumazenil
      significantly increased PN over frontocortical areas, indicating improved
      selective attention (p < 0.05). Increases in the P3 amplitude and MMN after drug
      treatment remained nonsignificant. Subjects felt more activated and extraverted
      after flumazenil treatment than after placebo (p < 0.05). Anxiety was not
      increased. The findings of this study confirm the concept that flumazenil
      administered at a low dose in humans exerts effects opposite to those of
      benzodiazepines.

PMID- 9617985
TI  - Naltrexone augmentation of neuroleptics in schizophrenia.
AB  - This study was conducted to determine whether the addition of naltrexone to
      ongoing neuroleptic treatment would facilitate the reduction in positive or
      negative symptoms in patients with schizophrenia. Twenty-one patients meeting DSM
      III criteria for schizophrenia were enrolled; all patients had been stabilized
      for at least 2 weeks on their dosage of neuroleptic medicine before entering the
      study. Patients were randomized to receive either placebo or naltrexone 200
      mg/day for 3 weeks in addition to their neuroleptic. Patients randomized
      initially into the placebo arm were crossed over to receive naltrexone in a
      single-blind fashion for 3 additional weeks. All patients were rated weekly with
      the Brief Psychiatric Rating Scale (BPRS). Fifteen patients received placebo and
      six received naltrexone in the first 3 weeks. No significant effects of
      naltrexone on total BPRS scores or BPRS subscale scores were observed. Patients
      who received naltrexone on a single-blind basis at the end of the placebo
      controlled trial demonstrated a transient exacerbation in negative symptoms as
      reflected by the total BPRS score and the BPRS Withdrawal-Retardation subscale
      score. Repeated-measures analysis of variance (ANOVA) on the BPRS total score of
      the subsequent treatment with naltrexone showed a trend for a significance in the
      drug by time effect. Repeated-measures ANOVA on the BPRS Withdrawal-Retardation
      subscale of the subsequent treatment with naltrexone showed a significant drug by
      time effect. The current data failed to indicate a clinical benefit when
      naltrexone was added to the neuroleptic regimen. Other potential applications of
      naltrexone in schizophrenia are addressed.

PMID- 9617986
TI  - Treating poststroke pathologic crying with fluoxetine.

PMID- 9617987
TI  - Low-dose mianserin in treatment of acute neuroleptic-induced akathisia.

PMID- 9617988
TI  - Venlafaxine augmentation with methylphenidate for treatment-refractory
      depression: a case report.

PMID- 9617989
TI  - Alprazolam is another substrate for human cytochrome P450-3A isoforms.

PMID- 9617990
TI  - Opioid detoxification with delta sleep-inducing peptide: results of an open
      clinical trial.

PMID- 9617991
TI  - Acute effects of low-dose flumazenil in panic disorder.

PMID- 9617992
TI  - Comments on article by Cowen and associates on treatment for tardive dyskinesia.

PMID- 9617993
TI  - Voluntary ethanol consumption in male adolescent hamsters increases testosterone
      and aggression.
AB  - The immediate and long-term biologic and behavioral consequences of voluntary
      ethanol (EtOH) exposure during male adolescence are unknown. In the present
      study, male golden hamsters voluntarily drank from a 15% EtOH solution in
      addition to consuming dry laboratory chow and water ad lib from Postnatal Day 25
      to Postnatal Day 43. Over this adolescent period, they drank an average of 13
      g/kg/day of EtOH, resulting in a mean blood EtOH concentration of ca. 53 mg %. On
      Postnatal Day 35, a period of enhanced sensitization and activation of the
      gonadal axis, testosterone levels were twice as high in EtOH animals than in
      sucrose-yoked controls. However, this difference disappeared by Postnatal Day 53,
      as EtOH and control animals showed comparable adult levels of plasma
      testosterone. When tested for aggression several days after the cessation of EtOH
      exposure, hamsters showed enhanced attack behavior toward smaller intruders
      placed into their home cage. These results suggest that voluntary EtOH exposure
      during male adolescence has specific neuroendocrine effects with lasting
      behavioral consequences.

PMID- 9617995
TI  - Inhibitors of fatty acid oxidation (mercaptoacetate, R-3-amino-4
      trimethylaminobutyric acid) stimulate feeding in mice.
AB  - Several lines of evidence indicate that fatty acid oxidation contributes to
      control of eating. We examined the effect of inhibitors of fatty acid oxidation
      (mercaptoacetate, R-3-amino-4-trimethylaminobutyric acid = emeriamine) on food
      intake in mice because fatty acid oxidation has been shown recently to increase
      the hepatic membrane potential in mouse liver, and this potential has been
      proposed to represent a signal for control of food intake. The effect of
      intraperitoneal injection of mercaptoacetate (200, 400, or 600 micromol/kg body
      weight) and emeriamine dihydrochloride (8.7, 17.4, 34.8, or 69.6 micromol/kg body
      weight) was investigated in mice fed a fat-enriched diet (18% fat). Both
      mercaptoacetate (400 or 600 micromol/kg) and emeriamine (34.8 or 69.6
      micromol/kg) significantly increased food intake. These results suggest that
      fatty acid oxidation is also involved in feeding control in mice. Therefore, the
      pertinent mechanisms can be studied in mice.

PMID- 9617994
TI  - Dietary fat type influences protein consumption in rats given 8-hydroxy-2-(Di-n
      propylamino)tetralin.
AB  - Our previous work indicates that type and level of dietary fat influences
      selection of protein and carbohydrate diets. Serotonin (5HT) appears to be
      involved in this feeding behavior. In the present study, we examined the effects
      of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on feeding behavior, and
      fenfluramine on in vitro 5HT and 5-hydroxyindoleacetic acid (5HIAA) release from
      the brain in rats fed tallow or corn oil. Male, Sprague-Dawley rats were given a
      diet containing corn oil or tallow for 2 days. In Experiment 1, rats received an
      injection of 8-OH-DPAT (a 5HT1A agonist) or saline and were then allowed to
      select from two diets: low protein/high carbohydrate or high protein/low
      carbohydrate. Prior exposure to tallow caused an increased intake of protein and
      8-OH-DPAT blunted this effect. In Experiment 2, the dorsal raphe from rats fed
      tallow or corn oil was superfused with fenfluramine or vehicle. Superfusates were
      collected for analysis of 5HT and 5HIAA. Fenfluramine increased serotonin release
      in tallow-fed animals as compared to basal. These results suggest that serotonin
      may be involved in mediating tallow's effect on macronutrient selection.

PMID- 9617996
TI  - Association of altered whole-body metabolism with locomotor sensitization induced
      by quinpirole.
AB  - Repeated exposure to drugs classed as psychostimulants can produce behavioral
      sensitization, defined as augmented motor responses to fixed doses of such
      compounds. For example, chronic treatment of rats with the dopamine D2/D3 agonist
      quinpirole increases the locomotor response to this drug to levels that are
      several times higher than after acute treatment. To determine if such enhanced
      activity is associated with changes in energy metabolism, one group of rats (n =
      16) received 11 injections of quinpirole (0.5 mg/kg every second day) while a
      second received equal numbers of saline injections. Immediately after each
      injection, rats were placed in individual metabolic chambers where oxygen (O2)
      consumption, carbon dioxide (CO2) output, and motor activity were measured every
      5 min for the next 2 h. Locomotor responses to quinpirole doubled during the
      course of treatment, thereby confirming the establishment of behavioral
      sensitization. The magnitude of energy metabolism and motor activity were
      positively correlated in control rats but not in quinpirole-treated rats.
      However, quinpirole reliably reduced respiratory quotient (CO2/O2). This suggests
      that enhanced utilization of body lipids could be a separate physiological
      consequence of quinpirole that might support in part the heightened locomotor
      activity characteristic of the behavioral sensitization it induces.

PMID- 9617997
TI  - Nitric oxide control of drinking, vasopressin and oxytocin release and blood
      pressure in dehydrated rats.
AB  - Intracerebroventricular (i.c.v.) injection of the inhibitor of NO synthase (NOS),
      N(G)-nitro-L-arginine methyl ester (L-NAME) (250 microg/5 microL) attenuated the
      drinking response in rats deprived of water for 24 h. Moreover, oxytocin (OT)
      levels in plasma increased after 2 min, whereas both oxytocin and vasopressin
      levels were elevated at 120 min after intracerebroventricular injection. The
      delayed effect of L-NAME on both hormones was not observed in dehydrated animals
      allowed to drink water. Blood pressure remained stable after injection of
      artificial cerebrospinal fluid (aCSF) in dehydrated rats not allowed to drink. In
      rats having access to water, however, there was an immediate but transient
      pressor response (0-5 min) with a delayed hypotension from 45 to 120 min. L-NAME
      consistently increased blood pressure in a biphasic mode, whether the animals
      drank or not, with an early peak at 5 min that decayed after 15-30 min and a
      second pressor response beginning at 30-45 min and remaining elevated at 120 min
      when the experiment ended. These pressor responses were independent of the
      adrenal glands. Thus, centrally produced nitric oxide facilitates drinking,
      inhibits release of vasopressin and oxytocin from the magnocellular system, and
      maintains resting arterial blood pressure in normally hydrated and dehydrated
      rats.

PMID- 9617998
TI  - Genetic sensitivity to 6-n-propylthiouracil and sensory responses to sugar and
      fat mixtures.
AB  - This study tested the hypothesis that genetic sensitivity to 6-n-propylthiouracil
      (PROP) is associated with greater sensitivity to sugar and fat in foods. Subjects
      were 118 young women from different ethnic backgrounds, mean age 26.9 years and
      mean body mass index (BMI) 23.4. The women were classified as nontasters (n =
      39), medium tasters (n = 48), or supertasters (n = 31) of PROP. Nontasters of
      PROP had thresholds of 1.8 x 10(-4) mol/L PROP or greater, whereas tasters had
      thresholds below 1.0 x 10(-4) mol/L PROP. PROP tasters were divided into medium
      tasters and supertasters, based on the ratio of intensity ratings of
      suprathreshold PROP solutions relative to NaCl solutions. Supertasters were
      defined as those with PROP/NaCl ratios of 1.90 or more. The pattern of sensory
      responses to sweetened dairy products of varying sugar and fat contents closely
      replicated data obtained in other studies. Genetic sensitivity to PROP was not
      associated with enhanced perception or altered hedonic response profiles for this
      range of 15 sugar/fat mixtures. Separating subjects into "likers" and "dislikers"
      of sweetened dairy products failed to reveal significant links to PROP taster
      status in this all-female sample.

PMID- 9617999
TI  - Effect of hepatic portal injection of ouabain on the hepato-sympathoadrenal
      reflex.
AB  - The purpose of the present investigation was to evaluate the effects of an
      intraportal injection of ouabain (2 mg/kg), an inhibitor of the sodium-potassium
      pump, on plasma catecholamine response in unrestrained normally fed rats with and
      without an intact hepatic vagus nerve. Three groups of rats were submitted to two
      injection conditions each. Hepatic vagotomized (HV) rats were randomly injected
      with ouabain or saline (0.9%) in the portal vein. Sham-operated rats were either
      injected with ouabain or saline in the portal or jugular vein. Ouabain or saline
      were injected at 0 min and again at 20 min. Plasma catecholamines were measured
      before the first injection and 15 min after each injection. Blood glucose
      concentrations were significantly (p < 0.01) increased by the ouabain injection
      as compared with basal values and saline-injected groups. The hyperglycemic
      effect of ouabain was not affected by the hepatic vagotomy or the site of
      infusion. The injection of ouabain, either into the portal or the jugular vein
      and either after HV or the sham operation, resulted in a significant (p < 0.01)
      increase in epinephrine levels as compared with saline-infused rats. Plasma
      norepinephrine levels were significantly (p < 0.05) increased after the second
      intraportal injection of ouabain in both HV and sham-operated groups. However,
      the injection of ouabain into the jugular vein did not change the plasma
      norepinephrine levels. The latter observation indicates a specific action of
      ouabain in the liver on the sympathetic activity.

PMID- 9618000
TI  - Differences in thermal salivation between the FOK rat (a model of genotypic heat
      adaptation) and three other rat strains.
AB  - Rats secrete saliva in response to heat. In the present study, details of thermal
      salivation were investigated using the FOK rat in comparison with Sprague-Dawley
      (SD), Donryu, and ACI rats. The FOK rat is a strain inbred for genotypic heat
      adaptation and endures heat for long periods. Conscious rats of all four strains
      were exposed to 42.5 degrees C. The order of heat endurance times at this
      temperature was FOK >> SD > Donryu = ACI. FOK rats spread their saliva over their
      entire ventral surface, their faces, and their outside legs. This saliva area was
      wider than those made by the other three strains. SD rats spread in an area wider
      than those of the Donryu and ACI rats. Saliva spreading in the FOK rats continued
      for 4.0-4.5 h, far longer than in the other strains. Under ketamine anesthesia
      and exposure to 40 degrees C, the FOK rats secreted saliva at 1390+/-235
      microL/100 g of body weight during a 60-min observation period. This was the
      highest rate among the four rat strains (p < 0.0001). The body temperature
      increase rate in anesthetized FOK and SD rats was lower than in the other two
      strains, suggesting a minor contribution of unknown factors. Ligation of the
      submandibular gland ducts abolished the thermal salivation of the FOK rats,
      whereas ligation of the parotid duct had no effect. The submandibular,
      sublingual, and lachrymal glands in the FOK rats were 1.3-1.5, 1.25-1.4, and 1.3
      1.5 times heavier, respectively, than those in the other three strains, whereas
      the parotid gland of the FOK rats was not enlarged. These findings indicate that
      the rats' saliva spreading and ET values are significantly correlated. A
      potentiated and long-lasting salivation from the submandibular gland was acquired
      during development of genotypic heat adaptation. This salivation is actuated in
      response to heat. The pronounced thermal salivation is probably attributable to
      adaptive changes in the superior salivatory nucleus-chorda tympani-submandibular
      gland pathway.

PMID- 9618001
TI  - Mouse running activity is lowered by Brucella abortus treatment: a potential
      model to study chronic fatigue.
AB  - Chronic fatigue syndrome, which can occur after acute infection and last for
      years, is characterized by severe and persistent fatigue. Others have reported
      decreases in mouse running activity following infection and have suggested this
      may provide an animal model for studying chronic fatigue. Voluntary running is a
      highly motivated activity in mice, which will often run 5-7 mi/day in our
      laboratory. Following 2 weeks of acclimation to running wheels with food and
      water available ad lib, female BALB/c mice received 0.2-mL tail vein injections
      of killed Brucella abortus (BA) or saline vehicle. Subsequently the effects on
      voluntary running and grooming behavior were determined. Injection of BA caused
      an immediate large decrease in running and a lack of grooming. Vehicle injections
      produced no changes in behavior. After the first several days of reduced running
      behavior, levels of running and grooming slowly returned back to normal over the
      next 2-4 weeks, with substantial individual differences in the rate of recovery.
      The pattern of running during recovery was intriguing in that BA mice first ran
      at normal levels just after the lights went out, but they stopped after only 1-2
      h. As recovery proceeded, they gradually increased the duration of the running
      bout during the night. Because this model uses voluntary exertion and the ability
      to run for longer periods of time characterizes recovery, the model may be a good
      one for studying the biologic underpinnings of chronic fatigue.

PMID- 9618002
TI  - Daytime vigilance after morning bright light exposure in volunteers subjected to
      sleep restriction.
AB  - This study was designed to test the hypothesis that bright light (BL) can have a
      stimulating effect on vigilance even in the absence of suppression of melatonin
      secretion and that this effect can be detected when measured in subjects with low
      vigilance levels. Seven normal subjects were exposed to bright-white light (BL
      group) and seven to dim-red light (DL group) on 2 consecutive days, each
      following a night of 4-h sleep restriction. The light treatment was administered
      in the late morning, between 0900 and 1330 hours. Salivary melatonin measurements
      indicated that BL did not suppress melatonin secretion or induce circadian phase
      shifts. The effects of the two treatments were compared on validated measures of
      daytime vigilance: immediate effects were evaluated on subjective alertness
      during the light treatment, whereas short-term (0.5-10.5 h) and long-term (20.5
      34.5 h) carryover effects were measured on subjective alertness, daytime sleep
      latencies (DSL), and psychomotor performance. After two nights of sleep
      restriction, subjective alertness and daytime sleep latencies decreased
      significantly, but there was no effect of the light treatment. BL treatment did
      not affect global performance, but there was an effect on the strategy used by
      the subjects, as shown by faster reaction times and increased percentage of
      errors in the BL group. It was concluded that daytime BL exposure did not have a
      stimulating effect on our measures of vigilance even in sleep-deprived subjects
      but that it may increase physiological arousal and affect the subjects' behavior
      in some specific performance tasks.

PMID- 9618003
TI  - Rats self-administer carbachol directly into the nucleus accumbens.
AB  - The potential reinforcing effect of the muscarinic cholinergic agonist carbachol
      within the nucleus accumbens (ACB) was examined in female Wistar rats by using
      the technique of intracranial self-administration. Rats dose dependently self
      administered solutions of 0.0-6.6 mM (in a volume of 100 nL per injection)
      directly into the ACB. Rats self-administered the 3.3 and 6.6 mM doses
      significantly more than the group given only vehicle. The caudate putamen did not
      support reliable self-administration of the 6.6-mM dose. Rats exhibited
      preference for the lever that produced infusions of 3.3 and 6.6 mM carbachol into
      the ACB over the lever that had no consequence. The self-infusion of the 6.6-mM
      dose into the ACB was inhibited by the coadministration of the muscarinic
      antagonist scopolamine (0.25 mM), but not by the nicotinic antagonist
      mecamylamine (6.6 mM). The present results suggest that direct activation of
      muscarinic receptors within the ACB supports self-administration and could result
      from reinforcement or from elicitation of a novel stimulus.

PMID- 9618004
TI  - Measurement of the three phases of muricidal behavior induced by delta9
      tetrahydrocannabinol in isolated, fasting rats.
AB  - Delta9-Tetrahydrocannabinol (THC) has long been recognized as inducing mouse
      killing behavior (muricidal behavior) in starving, isolated rats after a single
      injection. We showed that when the killing tendency was increased by THC, a
      preliminary contact with a mouse decreased the probability of muricidal behavior.
      By quantifying the three phases of the muricidal behavior in either nonkiller or
      naive THC-treated rats, we showed that the duration of each step was notably
      increased as compared to untreated natural killer rats, mainly the attack on the
      dead mouse, indicating increased aggressiveness. Finally, no significant changes
      were observed in the duration of the three phases in natural killer rats when the
      muricide assays were repeated every hour. In contrast, in THC-treated rats-
      either naive or nonkiller--all three phases decreased with the assay repetition
      to levels comparable to those of natural killer rats, suggesting that the killer
      behavior was progressively acquired for the six assays. These changes could be a
      useful model to study the central effects of THC and either its agonists or
      antagonists.

PMID- 9618005
TI  - Interindividual variability in Swiss male mice: relationship between social
      factors, aggression, and anxiety.
AB  - In the present study we carried out a series of experiments in Swiss albino male
      mice to investigate a) the effects of previous social experience on the levels of
      anxiety in the elevated plus-maze (EPM) and b) whether the response of males in
      the EPM differs in relation to the different social status. In Experiment 1 we
      tested in the EPM male mice that received different social experience. Results
      showed that individually housing generally increased measures of anxiety in the
      EPM compared with the group-housing condition. Moreover, aggressive males,
      screened during dyadic encounters in a neutral cage, displayed the highest levels
      of anxiety relative to the other experimental conditions. In Experiment 2 male
      mice remained group-housed and were observed to record their social status.
      Results showed that those animals rated as socially dominant displayed a higher
      level of EPM anxiety relative to subordinates. From an ethological perspective
      our findings may be interpreted in terms of coping strategies, with
      aggressive/dominant animals typified by higher levels of risk assessment and open
      arm avoidance than defensive/subordinate animals.

PMID- 9618006
TI  - Evidence that dark-phase hyperphagia induced by neurotoxin 6-hydroxydopamine may
      be due to decreased leptin and increased neuropeptide Y signaling.
AB  - Hyperphagia and obesity can be experimentally induced in rodents by
      microinjection of 6-hydroxydopamine (6-OHDA) into the ventral noradrenergic
      bundle (VNAB) to interrupt efferent catecholaminergic pathways to the
      hypothalamus. Since hypothalamic neuropeptide Y (NPY) is implicated in the
      control of ingestive behavior, we evaluated hypothalamic NPY activity in this
      model of obesity. Adult male rats injected bilaterally with 12 microg of 6-OHDA
      in the VNAB displayed an enhanced rate of body weight gain and selective dark
      phase hyperphagia that started at about 10 days postinjection and persisted for
      the entire duration of the experiment. NPY gene expression, assessed by
      ribonuclease protection assay, was significantly higher in the hypothalami of 6
      OHDA-treated hyperphagic rats during the dark phase (p < 0.01 vs. levels during
      the light phase and in control, vehicle-injected rats). We also evaluated gene
      expression of NPY Y and Y5 receptors, receptor subtypes reported to mediate NPY
      induced feeding. The dark-phase increase in NPY mRNA was accompanied by the
      concomitant upregulation of NPY Y5R gene expression, but not of Y1R mRNA levels.
      Leptin, the peripheral hormone secreted by adipocytes, is believed to maintain
      body weight and inhibit food intake, most likely by suppressing hypothalamic NPY
      activity. Evaluation of leptin gene expression in the epididymal fat revealed
      that the upregulation of leptin mRNA noted during the dark phase in control rats
      did not occur in 6-OHDA-treated rats. These observations implied that the normal
      restraint on NPY and feeding exercised by leptin in control rats may be abrogated
      in 6-OHDA-treated hyperphagic rats due to insufficient levels of leptin. If so,
      administration of leptin should inhibit food intake in these rats. Indeed,
      injection of leptin (2 mg/kg, intraperitoneally (i.p.)) on 2 consecutive days
      reduced 24-h food intake by 25% and significantly reduced body weight. These
      results suggest that the nocturnal hyperphagia and resultant obesity induced by 6
      OHDA injected into the VNAB may be attributed to leptin deficiency concomitant
      with increased hypothalamic NPY.

PMID- 9618007
TI  - Diurnally changing effects of locomotor activity on body temperature in
      laboratory mice.
AB  - In mice circadian body temperature curves are masked due to the effect of motor
      activity. However, body temperature will not immediately reflect activity, but
      rather the integrated activity over IT minutes (integration time) and after a
      certain delay (lag), and the sensitivity to such masking may change throughout
      the circadian cycle. The aims of the present investigation were to estimate IT
      and lag, to quantify the effect of motor activity on body temperature at
      different times of the day, and, using these results, to draw temperature curves
      that are closer to the endogenous one. Activity and body temperature of adult
      male laboratory mice were recorded telemetrically at 10-min intervals. Animals
      were housed in air-conditioned rooms (T = 22+/-2 degrees C; relative humidity: 55
      65%) with a light-dark cycle of 12 h:12 h (light from 0700 to 1900 hours) and
      food and water available ad lib. The diurnal activity and body temperature
      rhythms were similar with a main maximum during the dark time and a secondary
      maximum immediately following lights-on. Nearly all changes of activity were
      reflected in body temperature. IT and lag were established on the basis of the
      best correlation between body temperature and activity (overlapping 4-h sections
      of 12 days) for all combinations of IT from 10 to 90 min and lag from 0 to 50 min
      (10-min steps each). The overall means of IT and lag were 40 and 0 min,
      respectively. During the dark time the values were somewhat larger, but not
      significantly so. The correlation between activity and body temperature was
      significantly better in the light time compared to the dark time. The sensitivity
      of the body temperature to changes in activity was investigated by linear
      regression analysis for every hour over 12 days (IT = 40 min, lag = 0 min). The
      gradients assessed by regression analysis showed a diurnal pattern with maximal
      values during the light time (p < 0.01). Thus, body temperature was raised by
      activity more during the light time (minimum of body temperature and activity)
      than during the dark time. The intercepts showed a nearly sinusoidal diurnal
      pattern with maximal values in the middle of the dark time. Accepting that the
      intercepts correspond to zero activity at a certain time of day, one might use
      them to get a curve that is closer to the endogenous body temperature rhythm.
      Mechanisms (circadian and thermoregulatory) that might cause the diurnally
      changing sensitivity of body temperature to activity are discussed.

PMID- 9618008
TI  - Recurrent aggressive episodes entrain ultradian heart rate and core temperature
      rhythms.
AB  - The present study was designed to investigate the effects of recurrent aggressive
      episodes on the synchrony of autonomic circadian and ultradian rhythms. Eight
      aggressive male rats were entrained to a reverse 12 h:12 h light-dark cycle and
      then implanted with telemetry senders to continuously monitor heart rate (HR) and
      core temperature (Tc). The amplitude and the time of the peak (acrophase) for
      each of the circadian and ultradian oscillations were quantified by nonlinear,
      least-squares, multioscillator cosinor analysis that included the first four
      harmonics of the circadian rhythm. After recovery from surgery, the 3- and 5
      cycle/day ultradian rhythms of HR and Tc were the prominent ultradian components
      that were synchronized to the light-dark cycle. First, the resident males
      confronted a male intruder daily at lights-off (0800 hours) for a period of 3
      weeks. Second, after a 3-week recovery period, 15 daily aggressive confrontations
      were scheduled, with the intruders being introduced at 1200 hours. During the
      course of the confrontations the amplitude of 3- and 5-cycle/day oscillations in
      HR and Tc decreased, whereas the hemicircadian (2 cycles/day) rhythm amplitude
      doubled with minor changes of the circadian amplitude. The hemicircadian
      acrophase coincided with the time of the confrontation most clearly, and this
      alignment lasted for more than 1 week after the last social confrontation, even
      in the absence of a reminder. We interpret the synchronization of the
      hemicircadian acrophases to the time point of social confrontations as
      anticipating the physiological demands of the aggressive encounters.

PMID- 9618009
TI  - Thermal tolerance reduces hyperthermia-induced disruption of working memory: a
      role for endogenous opiates?
AB  - Previous reports indicate that microwave-induced hyperthermia can impair learning
      and memory. Here, we report that preexposure to a single 20-min period of
      hyperthermia can produce thermal tolerance and, thereby, attenuate future
      physiological and behavioral reactions to heating. Because endogenous opioids
      have been implicated in thermoregulation and reactions to microwave exposure, we
      also determined how opioid receptor antagonism might modulate these effects. In
      an initial experiment, rats were exposed daily, over 5 successive days, to 600
      MHz microwaves (at a whole-body specific absorption rate of 9.3 W/kg) or sham
      exposed. In animals exposed to microwaves, thermal tolerance was evidenced by
      declining rectal temperatures over time. Temperature reductions following
      microwave exposure were prominent after a single previous exposure. Therefore, in
      a second study, a single hyperthermic episode was used to induce thermal
      tolerance. On Day 1, rats were either exposed, over a 20-min period, to 600-MHz
      microwaves (at a whole-body specific absorption rate of 9.3 W/kg) or sham
      exposed. Just prior to radiation/sham-radiation treatment, rats received either
      saline or naltrexone (0.1 or 10 mg/kg, intraperitoneally (i.p.)). The following
      day (Day 2), rats were either microwave or sham exposed and tested on a task
      which measures the relative time subjects explore a familiar versus a novel
      stimulus object. Normothermic rats spend significantly more time in contact with
      new environmental components and less time with familiar objects. Brain (dura)
      and rectal temperatures were recorded on both days of the study. Microwave
      exposure produced a reliable hyperthermia which was significantly lower (on Day
      2) in rats receiving repeated treatments (tolerant group). On the behavioral
      test, rats exposed only once to microwave-induced hyperthermia (nontolerant
      group) exhibited significantly different patterns of object discrimination than
      did tolerant or sham-exposed animals. Sham-exposed and tolerant animals showed a
      distinct preference for the new object whereas the nontolerant animals did not.
      Naltrexone (10 mg/kg) antagonized the hyperthermia-induced disruption of the
      object discrimination task (in nontolerant rats) and produced patterns of object
      exploration that were similar to those of sham-irradiated and thermal-tolerant
      rats, suggesting that endogenous opioids play a role in the organism's response
      to heating. Taken together, these data are consistent with the conclusions that
      1) microwave-induced hyperthermia can cause a dose-dependent disruption of the
      normal discrimination between new and familiar objects, 2) physiological
      reactions to a single hyperthermic episode can produce a thermotolerance that
      expresses itself in both reduced levels of hyperthermia and attenuated behavioral
      disruptions following microwave exposure, and 3) opioid antagonism can partially
      reverse some of the behavioral effects of microwave-induced hyperthermia.

PMID- 9618010
TI  - Positive effects of acarbose in the diabetic rat are not altered by feeding
      schedule.
AB  - We previously demonstrated that chronic dietary treatment with acarbose, an alpha
      glucosidase inhibitor, improves glucose homeostasis in the streptozotocin (STZ)
      induced diabetic rat. In this study we evaluated the effects of 4 weeks of
      acarbose treatment on glucose homeostasis in STZ-diabetic rats for both meal-fed
      (three times daily) and ad libitum feeding conditions. Sprague Dawley male rats
      (n = 58) were started on a daily meal-feeding paradigm consisting of three 2-h
      feeding periods: 0700 to 0900 hours, 1300 to 1500 hours, and 1900 to 2100 hours.
      Following 2 weeks of adaptation, half of the animals were switched to ad libitum
      feeding. The feeding paradigm itself (meal fed versus ad lib.) affected neither
      body weight nor daily food intake. Twenty animals from each feeding group then
      received STZ (60 mg/kg i.v.), whereas control animals received vehicle injections
      only. Two days later, the diet of 10 STZ-treated animals from each paradigm was
      supplemented with acarbose (40 mg of BAY G 5421/100-g diet), and the groups were
      treated for 4 weeks. Untreated diabetic rats had lower body weight than vehicle
      injected control rats at all time points after STZ treatment. Acarbose treatment
      delayed this effect on body weight. STZ treatment induced hyperphagia regardless
      of feeding paradigm, which was significantly attenuated by acarbose only for the
      first week of treatment. Untreated diabetic rats had fasting blood glucose values
      4 times those of vehicle-injected controls in both the meal-fed and ad libitum
      fed conditions. Acarbose significantly lowered fasting blood glucose in the
      treated STZ groups. Blood glucose was also assessed 0, 90, and 180 min following
      the start of a meal. The postprandial rise in blood glucose was significantly
      reduced in acarbose-treated meal-fed diabetic rats, to values not significantly
      different from those of vehicle-injected control rats. During the fourth week of
      treatment glycated hemoglobin levels were significantly higher in untreated
      diabetic groups compared to vehicle-injected control groups. Acarbose treatment
      significantly reduced this rise, regardless of the feeding paradigm.
      Collectively, the results demonstrate that acarbose reduces diabetes-induced
      increases of blood glucose and glycated hemoglobin and that the glycemic effects
      of acarbose are most apparent during the absorptive period. Feeding paradigm (ad
      lib. versus meal fed) has little or no influence on acarbose's metabolic effects,
      indicating that large meals are not required to realize the beneficial effects of
      the drug. The meal-fed STZ-diabetic rat may be a good model with which to test
      meal-based diabetes treatments.

PMID- 9618011
TI  - Constant bright light (LL) during lactation in rats prevents arrhythmicity due to
      LL.
AB  - Light has a strong effect on the circadian system. Light-dark (LD) cycles are the
      main zeitgebers for practically all organisms, and the exposure of animals to
      constant bright light (LL) alters the manifestation of circadian rhythms. In
      rats, exposure to LL in adulthood produces an arrhythmic pattern in their motor
      activity, with a large number of ultradian components. In previous experiments,
      we found that rats born and kept under LL during lactation develop, after
      weaning, a circadian rhythm which is maintained for at least a couple of months.
      Here, we examined motor activity rhythms under LL of two groups of rats which
      differed in the lighting conditions under which they were kept during lactation:
      1) rats kept under LL during lactation (LL-rats), which manifested a circadian
      rhythm after weaning, and 2) rats kept under constant darkness (DD-rats), which
      were arrhythmic after weaning. We investigated whether the presence of
      rhythmicity under LL in LL-rats is a transitory effect or whether it persists
      throughout most of the life of the rat. Moreover, we examined motor activity
      rhythms of both groups of rats under different lighting conditions to find out
      other possible differences in the manifestation of their circadian rhythms.
      Results showed that there are no differences in the capacity of entrainment of
      both groups of rats to LD cycles or in the rhythm that rats show under DD. Most
      of the LL-rats maintained their circadian rhythms for the duration of the
      experiment (1 year), although we found differences in the rhythms manifested
      between males and females. We found that most of the LL-males became arrhythmic;
      consequently, at the end of the experiment, there were no differences in the
      number of males showing circadian rhythm in the LL- and DD-groups. Most of the
      females in the LL-group showed a clear circadian rhythm under LL during the
      entire experiment. Thus, LL during lactation has a protective effect against the
      disruptive effect of LL on the circadian rhythm, although it is only clearly
      manifested in females.

PMID- 9618012
TI  - Milking procedure alters the electrolyte composition of spontaneously
      hypertensive and normotensive rat milk.
AB  - A number of groups, including our own, have shown that the severity of
      hypertension expressed by the adult spontaneously hypertensive rat (SHR), which
      is primarily considered to be a genetic model of hypertension, can be reduced as
      a result of exposure to the behavioural and nutritional environment provided by a
      normotensive foster mother. It has been suggested that the hypertensive influence
      of the SHR dam may involve increased sodium delivery to the pups and there have
      been some reports of elevated sodium concentrations in the milk of SHR dams.
      However, these studies used either a long (> or =6 h) dam-pup separation period
      before collecting milk or repeated milking of the same dams, both of which have
      been shown to alter the trace element content of rat milk. Therefore, we have
      compared the electrolyte content of milk collected by these methods with milk
      derived from SHR and normotensive Wistar-Kyoto (WKY) dams separated from their
      litters for 2 h prior to a single-milking session. Long separation and repeated
      milking resulted in variable effects on the electrolyte content of both SHR and
      WKY dams' milk, compared with milk collected after 2 h from dams which had not
      previously been milked. The most notable effects were the abolition of
      significant strain differences, observed following 2-h separation, for milk
      sodium (WKY 22.1+/-1.4 vs. SHR 27.5+/-2.1 mmol/liter, p < 0.05) and calcium (WKY
      92.3+/-4.3 vs. SHR 69.4+/-2.9 mmol/liter, p < 0.05) when dams were separated for
      6 h or were serially milked. These data suggest that the electrolyte content of
      SHR and WKY dams' milk can be altered by the collection procedure and it is
      recommended that dams be milked on only one occasion following a short separation
      period from their litter.

PMID- 9618013
TI  - Body temperature daily rhythms in the striped mouse Rhabdomys pumilio: the
      effects of alpha and beta blockade.
AB  - Body temperature (Tb) daily rhythms and the effects of alpha and beta blockade
      were studied in the South African diurnal striped mouse Rhabdomys pumilio. Eleven
      mice (8 males and 3 females) with a body mass of 42.7+/-7.8 g (mean +/- SD) were
      tested. Mice were acclimated to a 13 h:11 h light-dark photoperiod at an ambient
      temperature of 25 degrees C. To assess the daily rhythm of pineal melatonin
      secretion, urinary 6-sulfatoxymelatonin (6-SMT) was determined. Mice displayed a
      robust Tb daily rhythm with an acrophase in the dark period, which is unexpected
      for a diurnal species. The nocturnal increase in Tb was accompanied by a
      significant rise in urinary 6-SMT. The beta blocker propranolol (4.5 mg/kg),
      injected 1 h before lights-off, resulted in a higher Tb value, whereas the alpha
      blocker prazosin (1 mg/kg) blocked the increase of Tb during the dark period.
      Prazosin also significantly attenuated the nocturnal increase of urinary 6-SMT.
      These results are in agreement with those obtained from the golden spiny mouse
      Acomys russatus and support the idea that small diurnal mammals retain the Tb
      rhythm of a nocturnal rodent. They also suggest that pineal melatonin secretion
      in these rodents is regulated by alpha rather than by beta receptors.

PMID- 9618014
TI  - Pair-bond disruption in Mongolian gerbils: effects on subsequent social
      behaviour.
AB  - Gerbils are social rodents which form stable male-female pairs. These pair bonds
      appear to be based on prolonged association rather than an exclusive mating
      relationship. However, both sexes contribute to territorial defense and pup
      rearing. Therefore, pair-bond disruption may be expected to have consequences for
      subsequent behaviour. This hypothesis was examined in a series of laboratory
      studies. Behavioural consequences of pair-bond disruption were seen in both sexes
      and the optimum housing parameters were found to be to pair males and females for
      5 weeks and to examine their behaviour 1 week after pair-bond disruption. Two
      further studies using these parameters were conducted to examine the combined
      influence of pair-bond disruption and the sex of the animal being interacted
      with. Results across all studies revealed a consistent pattern. Females showed
      increased immobility in contact, that is, freezing upon another animal's
      approach, and altered cage-orientated behaviour, regardless of the sex of the
      animal they were interacting with. In contrast, males showed decreased social
      investigation and offense and initiated fewer social interactions. However, these
      effects were only seen in interactions with other males. No changes in social
      behaviour were evident in interactions between pair-bond-disrupted males and
      females. The behavioural strategies of pair-bond-disrupted males and females in a
      social situation therefore differ. From these studies, it may be concluded that
      pair-bond disruption has consistent and reproducible effects on subsequent social
      behaviour in gerbils and that there are important sex differences in the
      behavioural expression of this.

PMID- 9618015
TI  - Repeated acquisition of a spatial navigation task in mice: effects of spacing of
      trials and of unilateral middle cerebral artery occlusion.
AB  - The working memory version of the Morris water escape task, the repeated
      acquisition task, consists of trial pairs in which an animal is started twice
      from the same start position. Animals have mastered this task when they need less
      time to find the platform in the second of the two trials. In this study, study,
      male C57BL mice were trained on this task with massed, spaced, or spaced delay
      trials in which there was a 90-min delay between the first and second trials of a
      pair. The mice trained with spaced trials learned the repeated acquisition task,
      whereas the mice trained with massed or spaced delay trials were not consistently
      able to do so. When the mice had reached a stable baseline performance, the
      middle cerebral artery (MCA) was occluded or the mice were sham-operated. Then,
      the effects of the MCA occlusion (MCA-O) on the performance in the repeated
      acquisition tasks were studied. MCA occlusion hardly affected the performance in
      this task, irrespective of the spacing condition of the trials, although surgery
      per se seemed to have a transient disruptive effect.

PMID- 9618016
TI  - Activity wheel running blunts increased plasma adrenocorticotrophin (ACTH) after
      footshock and cage-switch stress.
AB  - We examined whether chronic circadian physical activity attenuates hypothalamic
      pituitary-adrenal hormone responses after footshock with or without cage-switch
      stress. Young (45 g) male Fischer 344 rats were randomly assigned to individual
      suspended home cages (HC) or cages with activity wheels (AW) (12 h:12 h light
      dark photoperiod). After 6 weeks, each animal from a pair matched on mass (HC and
      AW) and average weekly running distance (AW) was randomly assigned to
      controllable or uncontrollable footshock on 2 days separated by 24 h. Half the
      animals were returned to the HC after the first day of shock, and half were
      switched to a new shoebox cage. One animal of each pair could end the shock for
      both rats by performing an FR-2 lever press. The yoked animal could not control
      the shock. After shock on Day 2, trunk blood was collected after decapitation.
      Plasma adrenocorticotrophin (ACTH), corticosterone, and prolactin were determined
      by radioimmunoassay. ANOVA for a 2 Group (AW vs. sedentary) x 2 Test
      (controllable vs. uncontrollable shock) x 2 Condition (HC vs. cage-switch) design
      indicated a Group x Test x Condition effect [F(1, 48) = 5.07, p = 0.03] and a
      Test main effect [F(1, 47) = 6.93, p = 0.01] for ACTH. ACTH was higher for
      sedentary animals after uncontrollable footshock under cage-switch conditions and
      higher after uncontrollable versus controllable footshock when averaged across
      groups and cage conditions. No effects were found for corticosterone or
      prolactin. Our results extend to activity wheel running prior findings of a cross
      stressor attenuation in plasma [ACTH] in response to cage-switch after treadmill
      exercise training, though the cross-stressor effect was additive with footshock.
      Consistent with our prior reports, the cross-stressor effect of wheel running was
      not apparent after footshock administered under home-cage conditions.

PMID- 9618017
TI  - Reliability and validity of a macronutrient self-selection paradigm and a food
      preference questionnaire.
AB  - Our laboratory has developed a macronutrient self-selection paradigm (MSSP)
      designed to vary fat content significantly and systematically with sugar, complex
      carbohydrates, and protein content in a battery of foods in which fat is commonly
      consumed in the American diet. We have also developed a food preference
      questionnaire (FPQ) according to an identical design but using a list of foods
      mutually exclusive of those presented for selection and intake in the MSSP. Men
      were tested twice on both instruments, with a 4-week interval between tests. It
      was determined that the MSSP has strong test-retest reliability for overall fat
      (r = 0.91) and other macronutrient intake and total caloric intake. In addition,
      hunger and fullness ratings were reproducible, and fat preferences (r = 0.99) and
      hedonic responses to foods listed on the FPQ were highly consistent across
      trials. This study also demonstrated that the MSSP is a valid instrument with
      respect to the men's reports of habitual intake of fat (r = 0.80) and total
      carbohydrates on the Block food questionnaire (FQ). In addition, men's fat
      preferences on the FPQ were validated with respect to overall fat (r = 0.86) and
      total caloric intake in the MSSP and fat intake (r = 0.83) reported on the Block
      FQ. The MSSP also has the capability to detect a wide range of fat intake (3.06
      50.35% among the present subjects), indicating that this instrument can identify
      individuals who differ markedly in fat intake or could detect changes in fat
      preference within subjects. In addition, this paradigm detected a large range of
      sugar and total caloric intake. It is anticipated that the use of these
      laboratory tools can enhance our understanding of the relationship between
      dietary fat intake and obesity.

PMID- 9618018
TI  - The sensory but not muscular pelvic nerve branch is necessary for parturition in
      the rat.
AB  - In the rat the pelvic nerve consists of a viscerocutaneous (sensory) branch which
      receives information from pelvic viscera and the midline perineal region, and a
      somatomotor (muscular) branch which innervates the ilio- and pubococcygeous
      muscles. To investigate the contribution of these branches to the parturition
      process, the length of gestation and course of delivery were closely monitored in
      43 pregnant, Wistar-strain rats randomly assigned to five groups: untreated
      control animals, animals in which the somatomotor branch of the pelvic nerve was
      bilaterally sectioned on Day 14 of gestation, animals in which the
      viscerocutaneous branch of the pelvic nerve was bilaterally sectioned on Day 14
      of gestation, animals treated similarly to the previous group but with young
      delivered by C-section at term, and sham-operated controls. Sectioning the
      viscerocutaneous branch seriously disrupted parturition and resulted in major
      dystocia and a high percentage of stillbirths in all females. In contrast,
      sectioning the somatomotor branch had no apparent effect on parturition and no
      significant differences were found between females of this group and sham or
      control dams on any of the measures recorded. It is concluded that the
      viscerocutaneous branch of the pelvic nerve is vital for the normal course of
      parturition in the rat but that the somatomotor branch plays little role, if any.

PMID- 9618019
TI  - Chronic corticosterone impairs memory performance in the Barnes maze.
AB  - Chronic stress has been reported to impair spatial memory and cause hippocampal
      impairment in rodents. Glucocorticoids are believed to be the active agent in
      this impairment. Studies have demonstrated that chronic glucocorticoid
      administration results in animals being impaired in the Morris water maze (MWM)
      or eight-arm radial maze. Although both of these methods are well established
      means of testing spatial memory, neither might be considered optimal for studying
      the behavioral effects of stress. The Morris maze is itself highly stressful to
      the animals. The eight-arm maze relies on a food reward to motivate the animals,
      and glucocorticoids have profound effects on hunger and satiety. We therefore
      investigated behavioral deficits of corticosterone-treated animals in the two
      previously used mazes and the Barnes circular platform maze (BCM), a test similar
      in design to the Morris maze, but one that does not require the animal to perform
      a highly stressful swim. Consistent with results in other tests, we found that
      animals that had been treated for 3 months with stress-equivalent concentrations
      of glucocorticoids showed significantly impaired behavior in the Barnes maze.

PMID- 9618020
TI  - Exogenous oxytocin attenuates suckling-induced prolactin release but not maternal
      or infant behavior in lactating rats.
AB  - The influence of exogenous oxytocin (OT) on maternal and infant behavior over 60
      min of suckling, which followed 6 h of isolation, was investigated on Day 12 of
      lactation in rats. Mothers administered 1 IU of OT or saline through an
      indwelling atrial catheter and their litters indicated a similar nursing and
      suckling pattern, which was estimated by the crouching time of the mothers and
      the number of stretch reactions performed by the litters during a suckling
      period. To assess the alteration of the suckling intensity by OT administration,
      the plasma prolactin (PRL) level was determined by an Nb2 lymphoma cell bioassay.
      In the control group, the plasma PRL level increased and reached a peak at 45 min
      after the onset of suckling in 60% of the animals. The suckling-induced PRL
      release was completely inhibited and/or markedly delayed by OT administration.
      The difference in body weight of the litters before and after a suckling period
      was estimated as an index of the amount of milk suckled by the litters. There was
      no difference in the amount of milk between the control and OT-treated groups
      during a 60-min suckling period. However, it was significantly greater in the OT
      treated group during the first 20 min of the suckling period. These results
      indicate that a dose of OT is a factor in the attenuation of the intensity of
      suckling done by the pups, whereas the nursing and suckling behavior is not
      influenced by OT administration.

PMID- 9618021
TI  - Salt taste responses of the IXth nerve in Sprague-Dawley rats: lack of
      sensitivity to amiloride.
AB  - To explore characteristics of the salt taste function of taste receptor cells
      located on the posterior tongue, we recorded electrophysiological responses from
      the whole glossopharyngeal nerve in Sprague-Dawley (SD) rats. For all salts,
      relative response magnitudes increased with increased stimulus concentrations
      (0.2-2.0 M) of NH4+, K+, and Na+ salts. The order of effectiveness of stimulation
      for Cl- salts was NH4Cl > KCl > NaCl. For sodium salts, relative response
      magnitudes were anion dependent. Sodium salts with small anions (NaCl, NaSCN, and
      NaNO3) had a much stronger stimulating effect than sodium salts with large anion
      groups (Na2SO4, C2H3O2Na, and C6H11O7Na). The responses of the glossopharyngeal
      nerve to the Na+ salts of NaCl, C2H3O2Na, and C6H11O7Na were not inhibited by the
      lingual application of the epithelial sodium transport blocker amiloride. This is
      in contrast to large amiloride sensitivity of the chorda tympani nerve. Amiloride
      also failed to inhibit the responses to K+ salts (KCl and KC2H3O2) and to NH4Cl.
      These results demonstrate that taste receptors innervated by the glossopharyngeal
      nerve in SD rats lack amiloride sensitivity as observed in the glossopharyngeal
      nerve of spontaneously hypertensive and Wistar-Kyoto rats. Furthermore, the
      difference between the small-anion group and the large-anion group of Na+ salts
      in their effectiveness to produce responses in the glossopharyngeal nerve
      parallels the effects noted for the anion dependence in the portion of the taste
      response resistant to amiloride in the chorda tympani nerve. Sodium salts with
      the smaller anion produced the larger responses in both glossopharyngeal and
      chorda tympani nerves after amiloride.

PMID- 9618022
TI  - Common polymorphisms in genes encoding the human mineralocorticoid receptor and
      the human amiloride-sensitive sodium channel.
AB  - We have examined the human mineralocorticoid receptor gene and the genes encoding
      the three subunits of the human amiloride-sensitive epithelial sodium channel.
      Eight new common polymorphisms were identified in these genes which may be useful
      in genotyping and linkage analysis.

PMID- 9618023
TI  - Oestradiol up-regulates oestrogen receptor, cyclophilin, and glyceraldehyde
      phosphate dehydrogenase mRNA concentrations in endometrium, but down-regulates
      them in liver.
AB  - Oestradiol regulates reproductive physiology and cardiovascular health in women.
      In the endometrium of ovariectomized ewes, previous work demonstrated that a
      single dose of oestradiol (50 microg) up-regulates oestrogen receptor-alpha (ER)
      and progesterone receptor (PR) gene expression within 24 h. Here we compared
      responses to different doses of oestradiol and different dosing regimens in two
      diverse tissues: endometrium and liver. ER, c-fos, cyclophilin and glyceraldehyde
      phosphate dehydrogenase (GAPDH) mRNA concentrations were analyzed on replicate
      RNA slot blots in both tissues, while PR and apolipoprotein AI (apo AI) mRNA
      concentrations were only analyzed in endometrium or liver, respectively. Along
      with ER mRNA, oestradiol strongly up-regulated GAPDH and cyclophilin mRNA
      concentrations in endometrium. In liver, however, oestradiol down-regulated them,
      along with apo AI mRNA. Responses to different doses and dose regimens, including
      repeated 50 microg doses, were similar to those evoked by a single 50 microg dose
      of oestradiol. Thus, oestradiol appears to have all-or-none effects which include
      up-regulation of ER, cyclophilin and GAPDH gene expression in endometrium and
      down-regulation of ER, apo AI, cyclophilin and GAPDH gene expression in liver.
      These results illustrate the sharp contrast between two mammalian tissues in
      their responses to physiological levels of oestradiol.

PMID- 9618024
TI  - Selenium regulates gene expression for estrogen sulfotransferase and alpha 2U
      globulin in rat liver.
AB  - Dietary intake of the essential trace element selenium (Se) regulates expression
      of genes for selenoproteins and certain non-Se-containing proteins. However,
      these proteins do not account for all of Se's biological effects. The objective
      of this work was to identify additional genes whose expression is regulated by
      Se. Identification of these genes may reveal new functions for Se or define
      mechanisms for its biological effects. Weanling male Sprague-Dawley rats were fed
      a Torula yeast-based Se-deficient basal diet or the same diet supplemented with
      0.5 mg Se/kg diet as sodium selenite for 13 weeks. Total RNA was used as template
      for RNA fingerprinting. Two differentially expressed cDNA fragments were
      identified and cloned. The first had 99% nucleotide identity with rat liver
      estrogen sulfotransferase (EST) isoform-6. The second had 99% nucleotide sequence
      identity with rat liver alpha 2u-globulin. The mRNA levels for both were markedly
      reduced in Se deficiency. Laser densitometry showed that EST mRNA in Se
      deficiency was 7.3% of that in Se-adequate rat liver. The level of alpha 2u
      globulin mRNA in Se-deficient rat liver was only 12.6% of that in Se-adequate rat
      liver. These results indicate that dietary Se may play a role in steroid hormone
      metabolism in rat liver.

PMID- 9618025
TI  - P450arom gene expression in peripheral blood lymphocytes: identification of a
      cryptic splice site for exon-1 after Epstein-Barr virus transformation.
AB  - The human aromatase gene (P450arom) is widely expressed, albeit in a tissue
      specific manner. In the present study, we measured aromatase activity and
      investigated the transcribed and translated products of the P450arom gene before
      and after Epstein-Barr virus (EBV) transformation in peripheral blood lymphocytes
      (PBLs) from normal individuals. Aromatase activity was determined by [3H]-delta4
      androstenedione (A) to [3H]-estrone (E1) conversion. Cellular total RNA and
      protein lysates were subjected to RT-PCR and Western analysis, respectively.
      Rapid amplification of cDNA ends (RACE) was used for the detection of novel 5'
      untranslated ends of the P450arom mRNA, which were subsequently sequenced and
      compared to the known transcripts of this gene. In untransformed PBLs, two known
      variants of exon 1 of the P450arom gene were expressed, corresponding to
      promoters PI.3 and PII, or 1c and 1d, respectively. In EBV-transformed PBLs, a
      cryptic splice site was revealed and a new 5'-untranslated product was found.
      RNase protection assay confirmed that this splice variant is not a RACE artifact.
      The 53 K P450arom protein was detectable in PBLs both before and after EBV
      transformation. We conclude that (i) the P450arom mRNA is present in human PBLs
      and (ii) EBV transformation of the latter leads to novel alternative splicing of
      the 5' end of this gene.

PMID- 9618026
TI  - 11Beta-hydroxysteroid dehydrogenase 1 in adipocytes: expression is
      differentiation-dependent and hormonally regulated.
AB  - 11Beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) catalyses the
      reversible metabolism of physiological glucocorticoids (cortisol, corticosterone)
      to inactive metabolites (cortisone, 11-dehydrocorticosterone), thus regulating
      glucocorticoid access to receptors. 11Beta-HSD-1 expression is regulated during
      development and by hormones in a tissue specific manner. The enzyme is highly
      expressed in liver, where it may influence glucocorticoid action on fuel
      metabolism, processes also important in adipose tissue. Here we show that 11beta
      HSD-1 is expressed in white adipose tissue, in both the adipocyte and
      stromal/vascular compartments, and in the adipocyte cell lines 3T3-F442A and 3T3
      L1. In these cells, 11beta-HSD-1 expression is induced upon differentiation into
      adipocytes and is characteristic of a 'late differentiation' gene, with maximal
      expression 6-8 days after confluence is reached. In intact 3T3-F442A adipocytes
      the enzyme direction is predominantly 11beta-reduction, activating inert
      glucocorticoids. The expression of 11beta-HSD-1 mRNA is altered in fully
      differentiated 3T3-F442A adipocytes treated with insulin, dexamethasone or a
      combination of the hormones, in an identical manner to glycerol-3-phosphate
      dehydrogenase (GPDH) mRNA (encoding a key enzyme in triglyceride synthesis and a
      well-characterised marker of adipocyte differentiation). The demonstration of
      11beta-HSD-1 expression in adipocytes and its predominant reductase activity in
      intact 3T3-F442A adipocytes suggests that 11beta-HSD-1 may play an important role
      in potentiating glucocorticoid action in these cells. 3T3-F442A and 3T3-L1
      represent useful model systems in which to examine the factors which regulate
      11beta-HSD-1 gene expression and the role of 11beta-HSD-1 in modulating
      glucocorticoid action in adipose tissue.

PMID- 9618027
TI  - Radioimmunoassay of free genistein in human serum.
AB  - Two radioimmunoassay (RIA) systems for genistein have been established, based on
      polyclonal antibodies against genistein-4'-O-(carboxymethyl)ether-bovine serum
      albumin and genistein-7-O-(carboxymethyl)ether-bovine serum albumin conjugates.
      The sensitivities of assays were 4.44 and 10.4 fmol (1.2 and 2.8 pg)/tube,
      respectively, the intraassay coefficients of variation ranged from 3.54 to 9.30%,
      the interassay C.V. varied from 6.72 to 19.7%, depending on the type of method
      and on genistein concentration. The cross-reactivities with other chemically
      related compounds (with exception of genistein derivatives at the position used
      for construction of the immunogen) were 5.5 and 6.1% for daidzein and 3.9 and
      0.04% for formononetin in RIAs using reagents prepared through positions 4'- and
      7- of genistein, respectively. The method was used for measurement of genistein
      levels in 26 omnivore subjects and in three volunteers after consumption of a
      meal prepared from 125 g of cooked whole soybeans. The values obtained in ether
      extracts from human sera were almost identical for both RIA systems, indicating
      that both RIAs measure the same entity.

PMID- 9618028
TI  - The development of A-ring modified analogues of oestrone-3-O-sulphamate as potent
      steroid sulphatase inhibitors with reduced oestrogenicity.
AB  - Steroid sulphatases regulate the formation of oestrogenic steroids which can
      support the growth of endocrine-dependent breast tumours. The development of
      potent steroid sulphatase inhibitors could therefore have considerable
      therapeutic potential. Several such inhibitors have now been developed of which
      the most potent to date is oestrone-3-O-sulphamate (EMATE). Unexpectedly, this
      inhibitor proved to be a potent oestrogen. In an attempt to reduce the
      oestrogenicity, whilst retaining the potent sulphatase inhibitory properties
      associated with this type of molecule, a number of A-ring modified derivatives
      were designed and synthesized. A-ring modified compounds included the 2-methoxy,
      2/4-nitro, 2/4-n-propyl and 2/4-allyl EMATE analogues. The ability of these
      derivatives to inhibit oestrone sulphatase activity was examined using placental
      microsomes. The allyl-substituted EMATE derivatives were more potent inhibitors
      than the propyl analogues but were all considerably less potent than EMATE. In
      contrast, the 2-methoxy and 2/4-nitro analogues were potent sulphatase inhibitors
      with 4-nitro EMATE being 5 times more active than EMATE. The 4-nitro, 2-methoxy,
      4-n-propyl and 4-allyl derivatives were also tested in vivo for their
      oestrogenicity and ability to inhibit sulphatase activity. While both 4-nitro and
      2-methoxy EMATE were potent inhibitors in vivo, 2-methoxy EMATE had no
      stimulatory effect on uterine growth in ovariectomized rats. The identification
      of a potent steroid sulphatase inhibitor lacking any oestrogenicity, such as 2
      methoxy EMATE, should be of considerable value in evaluating the potential of
      steroid sulphatase inhibition for breast cancer therapy.

PMID- 9618029
TI  - 1-Benzyl-2-phenylindole- and 1,2-diphenylindole-based antiestrogens. Estimation
      of agonist and antagonist activities in transfection assays.
AB  - In the 2-phenylindole system, the side chain at the nitrogen atom dominates the
      endocrine profile both in respect to the reduction of estrogenic action and the
      increase of antiestrogenic potency. In previous papers we reported on 2
      phenylindoles with aliphatic side chains and various functional groups [Biberger,
      C. and von Angerer, E., J. Steroid Biochem. Molec. Biol., 1996, 58, 31-43 and
      references therein]. In this study, we incorporated one or two phenyl rings into
      the side chain in order to lower the flexibility of the side chain. The sulfone
      group which was used as a polar function was linked to various positions of a
      benzyl or a phenyl group attached to the indole moiety. The relative binding
      affinities (RBA) ranged from 1.5 to 8.4% of estradiol. Agonist and antagonist
      activities were estimated in transfection assays using transiently transfected
      HeLa cells (cotransfected with the HEG0 vector) and stably transfected MCF-7/2a
      human breast cancer cells. The reporter plasmid contained the ERE from the
      Vitellogenin 2A gene, a viral tk promotor and the luciferase gene. Many of the
      new derivatives showed no or only very low estrogenic activity except for the
      compound 4e which contained two benzyl elements in the side chain. The
      antiestrogenic potency was very variable when concentrations 100-fold higher than
      that of estradiol were applied. The compound with the para-substituted benzyl
      fragment (4b) proved to be a pure antagonist in the transfection assays. It
      antagonized the effect of estradiol (10 nM) with an IC50 value of 10(-7) M. It
      also inhibited strongly the growth of estrogen-sensitive human MCF-7 mammary
      carcinoma cells (IC50, 3 nM). Its activity was comparable to the one of the
      corresponding aliphatic 2-phenylindole derivative ZK 164.015. The data from the
      transcription and proliferation assays suggest that a phenyl ring can be
      incorporated into the side chain of pure antiestrogens without reducing their
      potency, provided the aromatic ring is para-substituted and a methylene group
      between the indole nitrogen and the phenyl group can act as hinge.

PMID- 9618030
TI  - Estrogen- and antiestrogen-responsiveness of HEC1A endometrial adenocarcinoma
      cells in culture.
AB  - HEC1A endometrial cancer cells express the wild-type form of the estrogen
      receptor (ER) and 17beta-estradiol (E2) induces proliferation of these cells. In
      contrast, tamoxifen only causes a minimal increase (<20%) in cell proliferation.
      In HEC1A cells transiently transfected with the C3-Luc plasmid derived from the
      complement C3 gene, both E2 and tamoxifen exhibited ER agonist activity and
      tamoxifen was also a partial antagonist for this response. The relative ER
      agonist/antagonist activities of E2, tamoxifen and ICI 182,780 were also
      investigated in HEC1A1 cells transiently transfected with two E2-responsive
      plasmids, pCATHD-CAT and pCKB-CAT which contain 5'-promoter inserts from the
      cathepsin D and creatine kinase B genes, respectively. The results showed that E2
      and tamoxifen induced reporter gene activity in cells transiently transfected
      with both constructs. ICI 182,780 exhibited partial ER agonist activity only in
      cells transiently transfected with pCKB-CAT and antagonized E2-induced reporter
      gene activity using both the CKB- and CATHD-derived constructs. These results
      demonstrate that HEC1A endometrial cancer cells are E2-responsive and represent a
      useful cell culture model for understanding hormone/antihormone-induced
      endometrial cell responses.

PMID- 9618031
TI  - A monoclonal antibody to oestradiol potentiates the stimulation of the specific
      activity of the brain type creatine kinase by oestrogen in vivo and in vitro.
AB  - We described previously the in vivo immunoneutralization effects of a high
      affinity anti-oestradiol antibody clone 15 in blocking ovulation and synaptic
      remodeling in cycling female rats. In the present study we report the enhancing
      effects of this antibody. Treatment of ovariectomized female rats or female
      derived skeletal cell cultures in vitro with anti-E2 15 plus oestrogen (E2)
      potentiated the specific activity of the brain type creatine kinase (CK) response
      to E2 in the rat tissues or skeletal cells. The enhancing CK response of anti E2
      15 plus E2 was time- and dose-dependent in the uterus, thymus, epiphysis and
      diaphysis of ovariectomized female rats. In the pituitary, on the other hand,
      anti-E2 15 blocked the stimulatory CK response to E2. Two other high affinity
      anti-E2 antibodies, clones 8D9 and 11B6, had no effect in augmenting the response
      of CK to E2 in rat tissues. Moreover, the enhancing CK response in rat tissues
      was specific to anti-E2 15 plus E2 since the intact anti-E2 in the presence of
      other oestrogen mimetics, such as oestriol or stilbestrol or tamoxifen did not
      potentiate the CK response in rat tissues. In this model system the Fab' monomer
      of anti-E2 15 abolished the CK response to E2 in rat tissues and not to anti-E2
      15 plus E2 whereas tamoxifen completely blocked the CK response to anti E2 plus
      E2. Anti E2 15 may therefore serve as a specific carrier in delivering E2 to
      oestrogen sensitive rat tissues or cells containing functional oestrogen
      receptors and thereby increasing the magnitude of E2 effects in vivo and in
      vitro.

PMID- 9618033
TI  - An audit of care provided for children with epilepsy in the South Tees area.
AB  - This study examined the knowledge carers of children with epilepsy have of the
      condition and its management. It also examined their experience of medical
      services for their child and the attitude of staff at their schools. A school
      nursing sister using a semi-structured technique interviewed 48 carers of 53
      children. A majority expressed dissatisfaction with outpatient medical care,
      especially that outpatient visits did not improve their knowledge of the
      condition or its treatment. Twenty-eight carers were not satisfied with the
      attitude of staff at schools. Ways to improve the service are discussed,
      including the role of the specialist community children's nurse and the need to
      see children with epilepsy in a dedicated clinic.

PMID- 9618032
TI  - Strain differences in adrenal microsomal steroid metabolism in guinea pigs.
AB  - We recently reported that CYP2D16, a xenobiotic-metabolizing P450 isozyme, was
      expressed at higher levels in adrenal microsomes from inbred Strain 13 guinea
      pigs than in those from outbred English Short Hair (ESH) animals. Studies were
      done to determine if there also were strain differences in adrenal microsomal
      steroid metabolism. In both inner (zona reticularis) and outer (zona fasciculata
      plus zona glomerulosa) zone preparations of the adrenal cortex, 21-hydroxylase
      activities were greater in microsomes from ESH than from Strain 13 guinea pigs.
      By contrast, 17alpha-hydroxylase activities were similar in the two strains. In
      both strains, 21-hydroxylase activities were greater in inner than outer zone
      microsomes, but the opposite was found for 17alpha-hydroxylase activities
      (outer>inner). Northern and Western analyses revealed higher levels of CYP21 mRNA
      and protein in adrenals from ESH than Strain 13 guinea pigs, but there were no
      strain differences in CYP17 mRNA or protein concentrations. Despite the zonal
      differences in adrenal 17alpha-hydroxylase and 21-hydroxylase activities, CYP17
      and CYP21 mRNA and protein levels were similar in the inner and outer zones
      within each strain of guinea pig. The results demonstrate strain differences in
      microsomal steroid metabolism that are explained by differences in CYP21
      expression. By contrast, the zonal differences in steroid hydroxylase activities
      may be attributable to post-translational mechanisms.

PMID- 9618034
TI  - Outcome of recommendations for augmentative communication in children.
AB  - Some children with severe motor disorders have unintelligible speech, and may be
      recommended augmentative communication systems, such as a symbol chart or a voice
      output aid. The paper reports the outcome after 15-18 months for 35 children of
      recommendations for augmentative communication. Using structured questionnaires,
      parents were asked whether equipment was provided as recommended. Their
      perception of success in children's use of augmentative aids was recorded and
      related to potentially influential factors. Twenty-five symbol systems, 10 speech
      output devices and 11 switches were received; 18 symbol systems were used for
      communication and 10 were used frequently. Seven speech output devices were used
      for communication but only two were reported to be used frequently. Factors
      leading to more successful outcomes include early receipt of the aid, perceived
      adequate local training in the use of the aid, and children aged 6 years or more
      at initial assessment. The findings also suggest that referring professionals
      will need to be better informed about the nature and limitations of augmentative
      communication aids, and that improved local professional input and careful
      interagency planning and co-ordination are required to achieve optimal outcome.

PMID- 9618035
TI  - How easy is it for young people to obtain cigarettes, and do test sales by
      trading standards have any effect? A survey of two schools in Gateshead.
AB  - Smoking prevalence among young people continues to rise and cigarettes are easily
      available from many shops. Test sales are used by trading standards departments
      to try to reduce under-age sales, but it is not known whether this has any real
      impact on cigarette purchase and consumption. This study aims to evaluate the
      impact of test sales on purchase and consumption of cigarettes by young people. A
      survey of two schools in Gateshead, one in the intervention area and one acting
      as a control was carried out. A series of test sales were targeted to shops
      within 1.5 km of the intervention school. A questionnaire was administered in
      both schools among year 10 pupils, age 14-15 years, prior to the intervention and
      again 1 year later. The outcomes measured were number of successful test sales,
      reported availability of cigarettes and change in smoking prevalence following
      the intervention. Some 224 pupils from both schools were surveyed in 1995 and 163
      pupils from the new cohort of year 10 pupils in 1996. Prior to the intervention,
      the levels of regular smoking in the intervention school were 39% for girls and
      26% for boys. In the control school these levels were 24% and 14%, respectively.
      The intervention by trading standards resulted in no purchases and hence no
      prosecutions, but children reported being able to buy cigarettes with ease from
      the nearby shops; only three (2.5%) reported sales refused in 1995 and five
      (5.8%) in 1996. Not surprisingly there was no significant change in smoking
      prevalence in either school in 1996. This study suggests that test sales may not
      be effective in modifying cigarette availability to young people and that they
      are not a reliable measure of access to cigarettes by children.

PMID- 9618036
TI  - The relationship between the treatment of cough during early infancy and maternal
      education level, age and number of other children in the household. ALSPAC Study
      Team. Avon Longitudinal Study of Pregnancy and Childhood.
AB  - The main objective of this study was to investigate how the consultation rate and
      medication use in the treatment of cough symptoms in infants during their first 6
      months of life varied by their mothers' education levels, ages and the presence
      of other children in the household. A prospective cohort of children were studied
      from birth. Data were collected by means of self-completion postal
      questionnaires. All 6682 children born between 1 July 1991 and 30 June 1992,
      inclusive within the three health districts of former Avon which are within the
      South-west Regional Health Authority were included in the study. The proportion
      of children ever having a cough during their first 6 months of life and of those
      with cough symptoms, the proportion receiving cough medicine and the proportion
      consulting a doctor was investigated. Some 61% of children were reported as
      having had a cough during their first 6 months of life and this proportion did
      not vary significantly across educational levels. The proportion of children with
      coughs who were taken to a doctor (60%) and the proportion with coughs who were
      given cough medicine (20%), however, did vary with education. The association
      between mother's education level and the treatment of her child's cough was much
      stronger than with either of the mother's age or number of other children. After
      controlling for confounding factors, the percentage of mothers who consulted a
      doctor for their children's coughs decreased progressively with increasing
      maternal education from 70% (95% confidence interval: 66%, 73%) of those with CSE
      or less to 50% (95% CI: 45%, 55%) of those with a degree. A similar pattern
      emerged with the use of cough medicine, 22% (95% CI: 19%, 25%) of children whose
      mothers were in the lowest education group received cough medicine compared with
      12% (95% CI: 9%, 15%) in the highest group. A large proportion, 60%, of children
      under 6 months with coughs are taken to a doctor. Children of more highly
      educated mothers are less likely to see a doctor or to receive cough medicine.

PMID- 9618037
TI  - Diet during pregnancy in relation to birthweight in healthy singletons.
AB  - We have investigated the relationship between consumption of food groups and
      intake of energy-generating macronutrients on the one hand, and birthweight on
      the other among apparently healthy singleton, term babies. Three hundred and
      sixty-eight women who delivered in six maternity clinics in two Greek cities
      during specified days over an 8-month period completed a 190-item, interviewer
      administered, validated, semiquantitative food frequency questionnaire. Study
      participants also provided information on sociodemographic, reproductive and
      lifestyle variables. Data were analysed using multiple regression modelling.
      Nutritional variables were energy-adjusted, and non-nutritional correlates of
      birthweight were accounted for. The analysis revealed most of the established non
      nutritional associations of birthweight -- an indication of study validity. Among
      food groups, meat and meat products and fish and sea food were suggestively
      associated with increased birthweight (two tailed P-values 0.08 and 0.16,
      respectively). Among energy-generating nutrients, monounsaturated fat was
      positively associated with birthweight and significantly so in several of the
      models. We consider our findings are considered as compatible with hypotheses
      linking fish and meat intake to fetal growth and as indicative of a positive
      association between intake of monounsaturated fat and birthweight.

PMID- 9618038
TI  - Repressive adaptation in children with cancer: it may be better not to know.

PMID- 9618039
TI  - Mutant p53 correlates with reduced expression of thrombospondin-1, increased
      angiogenesis, and metastatic progression in melanoma.
AB  - On the basis of reports linking mutant p53 (mp53) to decreased expression of the
      angiogenesis inhibitor thrombospondin-1 (TSP-1) and increased angiogenesis, we
      compared primary and metastatic melanoma tumor specimens to determine if these
      factors were associated with metastatic progression. Western blotting,
      immunohistochemistry (IHC), and image analysis (IA) techniques were employed to
      evaluate the relationship between p53 status and TSP-1 expression in Zaz and M14
      melanoma cell lines, and among p53, TSP-1, and angiogenesis in primary and
      metastatic melanomas. Zaz cells expressed wild-type p53 (WT p53) and high levels
      of TSP-1, while the M14 cells expressed mp53 and low TSP-1 levels. Examination of
      clinical melanoma specimens (N = 99) revealed an incidence of mp53 of 48%.
      Specimens with WT p53 (N = 46) expressed significantly higher mean levels of TSP
      1 (41 +/- 27 vs. 21 +/- 24; p = 0.0004), and lower microvessel counts per 200x
      field (25 +/- 17 vs. 40 +/- 20; p = 0.0001) than tumors expressing mp53 (N = 42).
      A significantly higher incidence of mp53 expression was seen in metastatic tumors
      (64%, 37/58) than in primary tumors (27%, 11/41)(p < 0.0005). Primary tumors
      specimens had higher levels of TSP-1 (40 +/- 27 vs. 25 +/- 25; p = 0.0054) and
      lower microvessel counts (26 +/- 18 vs. 39 +/- 20, p = 0.0013) than metastatic
      tumors. These data suggest that acquisition of mp53, decreased TSP-1, and
      increased microvessel infiltration may be interrelated and associated with the
      metastatic phenotype in malignant melanoma.

PMID- 9618040
TI  - Alcohol-stimulated promotion of tumors in the gastrointestinal tract.
AB  - Alcohol is a major risk factor for cancers of the upper gastrointestinal tract
      but the association with cancers of the large bowel is not as clearly
      established. In recent studies, we have provided experimental support for the
      associations in the esophagus and oral cavity. Our studies also indicate that the
      tumor promotion ability of ethanol is related to its ability to generate oxygen
      free radicals as measured by an increase in indices of lipid peroxidation. This
      increase in lipid peroxidation was evident in the liver as well as the tissues
      targeted by the site-specific carcinogens and promoted by ethanol. Studies in
      mice showed that the increased lipid peroxidation as well as tumor incidence was
      inhibited by the administration of vitamin E, the potent antioxidant.
      Determination of fatty acid profiles showed significant alterations when ethanol
      was used as a tumor promoter after treatment with the carcinogen. Ethanol as a
      promoter caused an increase in esophageal polyunsaturated fatty acids (PUFA).
      Ethanol promotion was also evident in increased arachidonate and an exaggeration
      in PUFA that are involved in eicosanoid production. Thus, these results suggest
      that ethanol-related promotion may be the result of excessive cell proliferation
      induced by disordered lipid and eicosanoid metabolism that may cause a selective
      outgrowth of the carcinogen-initiated cells. Supporting evidence for ethanol
      induced hyper-regeneration is also reviewed.

PMID- 9618041
TI  - Formation of nitrosamines during consumption of nitrate- and amine-rich foods,
      and the influence of the use of mouthwashes.
AB  - We studied the formation of carcinogenic nitrosamines during consumption of food
      rich in nitrate and amines, and its possible inhibition by use of an
      antibacterial mouthwash. Twelve volunteers were fed a diet containing the high
      nitrate vegetables lettuce or spinach during two periods of four consecutive
      days, in combination with fish products containing high levels of amines as
      nitrosatable precursors. During the two periods, the subjects used an
      antibacterial mouthwash containing chlorhexidine or a control mouthwash without
      antibacterial activity. Twenty-four-hour urine samples were collected after
      consumption of the meals, and saliva samples were collected 1 h after each meal.
      The nitrate and nitrite contents of the urine and saliva samples were determined
      by spectrophotometry (for nitrite) and HPLC (for nitrate). The concentrations of
      volatile nitrosamines in the urine samples were determined by gas chromatography
      mass spectrometry. Significant increases in mean urinary nitrate levels (from 59
      to 135 mg/24 h) and in mean salivary nitrate levels (from 10 to 56 microg/ml) and
      salivary nitrite levels (from 2 to 11 microg/ml) were observed during the
      consumption of food rich in nitrate and amines, as well as a significant increase
      in the mean urinary excretion of total examined volatile nitrosamines (from 2 to
      7 nmol/24 h) and of N-nitrosodimethylamine (from 1.2 to 2.9 nmol/24 h). Use of
      the antibacterial mouthwash resulted in a decrease in mean salivary nitrite
      levels from 16 to 3 microg/ml and a decrease in mean urinary excretion of N
      nitrosomorpholine (from 7.0 to 0.3 nmol/24 h). For the whole data set,
      significant correlations were observed between nitrate intake in food and urinary
      nitrate (p = 0.01; r2 = 0.07) and between urinary nitrate and urinary N
      nitrosodimethylamine (p = 0.002; r2 = 0.11). In conclusion, consumption of a diet
      rich in nitrate and amines increases the risk of formation of carcinogenic
      nitrosamines. Use of an antibacterial mouthwash containing chlorhexidine can
      result in inhibition of nitrosamine formation.

PMID- 9618042
TI  - Aspirin use and p53 expression in colorectal cancer.
AB  - p53 protein overexpression indicates loss of tumor suppressor activity and is the
      most common genetic alteration in colorectal neoplasms. Epidemiologic and
      experimental studies suggest that regular use of aspirin may reduce colorectal
      cancer risk. We set out to determine whether p53 overexpression of the colorectum
      was associated with a patient's history of aspirin use. Self-administered
      questionnaires, including information on aspirin use, were obtained from 163
      patients with nonfamilial colorectal cancer and from 326 healthy controls.
      Nuclear p53 protein overexpression using anti-p53 CM-1 polyclonal antibody was
      observed in 44.8% (73/163) of patients' tumors. A nonsignificant inverse
      association was observed between use of aspirin and colorectal cancer. Compared
      with that for nonusers, the odds ratio (OR) for individuals who took aspirin at
      least twice weekly was 0.68 (95% confidence interval [95% CI]: 0.39-1.18). The
      odds ratio for those individuals who used aspirin for less than 5 years was 0.54
      (95% CI: 0.24-1.23), and 0.80 (95% CI: 0.42-1.51) for those who used aspirin for
      5 years or more, when compared with nonusers. An inverse association of regular
      aspirin use (two times per week or more) was found both for cases with p53
      overexpression (OR: 0.79; 95% CI: 0.39-1.59), and for cases without p53
      overexpression (OR: 0.56; 95% CI: 0.25-1.22). There was little evidence of a
      difference in the effect of aspirin use on cancer risk between cases with and
      without p53 overexpression, even after adjustment for potential confounders.

PMID- 9618043
TI  - Antitumor effect of medium-chain triglyceride and its influence on the self
      defense system of the body.
AB  - Medium-chain triglyceride (MCT), long-chain triglyceride (LCT), and their mixture
      were compared in reference to both cytotoxic effect against human tumor cells and
      influence on the immune system. MCT showed more potent cytotoxicity than LCT.
      Continuous contact with MCT also inhibited the cytotoxic effect of lymphokine
      activated killer (LAK) cells much more strongly than LCT. However, there is a
      discrepancy between the concentration of MCT, or the mixture, that could suppress
      the growth of tumor cells and the concentration that inhibited the cytotoxicity
      of LAK cells. Moreover, no damage was observed in PBL or LAK cells or in their
      cytotoxicity when the cells were incubated with TG for 2 h a day. Thus, short
      term contact with TG could inhibit tumor growth while immune system was
      maintained within normal range. Clinically fine control of the concentration of
      injected triglycerides, especially MCT, can be expected to provide potent
      antitumor effect and maintenance of normal immune system.

PMID- 9618044
TI  - Multiple mechanisms of action of the benzamides and nicotinamides as sensitizers
      of radiotherapy: opportunities for drug design.
AB  - The benzamides and nicotinamides are a well-known class of drugs that contain
      many analogs having radio- and chemosensitizing properties. This study reports on
      a structural analysis in order to explain the chemical features important to
      their mechanisms of action. In general, N-substituted analogs are distinguished
      from the non-N-substituted analogs because they (i) are susceptible to
      radiolysis, (ii) induce cytotoxicity by apoptosis but not necrosis, (iii) inhibit
      cell proliferation, (iv) activate poly adenosine diphosphate ribosyl transferase
      (poly ADPRT), and (v) have a much-reduced effect on microregional tumor blood
      perfusion. It was concluded that the mechanism of action of N-substituted analogs
      is shifted from primary effects on tumor vascularization as is seen with the non
      N-substituted analogs to one where radiosensitization can be explained by
      selective induction of apoptosis via radiolysis and accumulation of DNA damage.
      This knowledge may be useful in the design of drugs possessing multiple
      mechanisms of radiosensitizing action.

PMID- 9618045
TI  - Circulating levels in serum of total sialic acid, lipid-associated sialic acid,
      and fucose in precancerous lesion and cancer of the oral cavity.
AB  - Total sialic acid (TSA), lipid-associated sialic acid (LASA), and fucose were
      estimated in sera of 35 patients with precancerous lesion of the oral cavity, 68
      patients with cancer of the oral cavity, and 25 age- and sex-matched non-chewers
      of both tobacco and betal nut and nonsmokers as controls. Significant elevation
      in the serum levels of TSA and LASA were observed in patients with the
      precancerous and cancer lesions when compared with the controls. Serum TSA levels
      were elevated significantly in patients with cancer when compared with those with
      precancerous lesions. Circulating TSA and LASA levels were found to reflect tumor
      burden and correlated well with stage of the disease. However, serum fucose
      levels did not show an increase corresponding to stage of the disease. The
      results suggests that combined evaluation of these markers may be useful in
      predicting early malignant change and also in assessing the spread and
      invasiveness of the disease in cancer of the oral cavity.

PMID- 9618046
TI  - Oncogene and suppressor gene expression as a biomarker for ethylene oxide
      exposure.
AB  - Ethylene oxide is a proven genotoxic chemical, and there is lots of evidence
      suggesting its carcinogenic effects in humans. The unexpected massive appearance
      of a certain tumorous cluster in personnel exposed to ethylene oxide in a
      Hungarian county hospital focused attention on the effects of this toxic gas.
      Since we had developed an animal model for the investigation of alterations in
      onco/suppressor gene expression due to external carcinogenic agents, and this
      model had already been used to evaluate the carcinogenic effects of cytostatic
      drugs in humans, an analysis of the effects of ethylene oxide exposure seemed to
      offer further information on the usefulness of gene expression as a biomarker.
      The main purpose of our study was to determine whether or not ethylene oxide
      exposure causes an elevated expression of onco/suppressor genes in the white
      blood cells of exposed people. Two different exposed groups and one control group
      were included in the study. The N-ras and p53 genes were chosen for the
      investigations of gene expression. N-ras is known to be activated in several
      tumor types, and p53 is also involved in carcinogenesis and plays an important
      role in the cellular answer mechanism to exogenous toxic effects. RNA was
      isolated from the white blood cells, slot blotted onto nitrocellulose membranes,
      and hybridized with chemoluminescently labeled gene probes. The results were
      detected on X-ray films and scanned into a computer, and relative risk for
      elevated gene expression was calculated in each group. Elevated N-ras and
      detectable p53 expressions were observed more frequently in both exposed groups
      compared with the control group (relative risks--N-ras: 1.57 [0.77-3.22] and 2.34
      [1.21-4.52]; p53: 6.67 [2.35-18.92] and 6.06 [2.10-17.49]).

PMID- 9618047
TI  - Relations of nm23 expression to clinicopathologic variables and proliferative
      activity of gastric cancer lesions.
AB  - Relationships of nm23 expression and 12 clinicopathologic variables and
      proliferative activity of cancer cells were examined in 55 gastric cancer
      patients to clarify the effects of nm23 expression on the factors and activity in
      gastric cancer. Expression of nm23 was determined by immunohistochemically
      stained sections using a monoclonal antibody, nm23H-1. Proliferative activity was
      immunohistochemically evaluated by proliferating cell nuclear antigen (PCNA)
      labeling index (LI) using a monoclonal antibody PC10. Expression of nm23 was
      found in 24 lesions (positive group) but not in 31 lesions (negative group). With
      regard to clinicopathologic variables, a significant (p < 0.05) difference
      between the positive and negative groups was found in 1 of the 12 factors, depth
      of cancer invasion. PCNA LI (48.9 +/- 11.6%) of the former group was
      significantly (p < 0.05) higher than that (40.3 +/- 12.6%) ot the latter,
      although multiple regression analysis showed that nm23 expression was not one of
      the most influencing variables for PCNA LI. The results may suggest that
      expression of nm23 in gastric cancer lesions is correlated to tumor progression
      and/or proliferation rather than suppression of metastasis.

PMID- 9618048
TI  - Cyanine fluorochrome-labeled antibodies in vivo: assessment of tumor imaging
      using Cy3, Cy5, Cy5.5, and Cy7.
AB  - Monoclonal antibodies to two different targetable antigens were conjugated to
      each of four commercially available cyanine fluorochromes. Equal amounts of all
      four antibodies were coinjected into tumor-bearing animals and imaged. Small,
      superficial tumors were adequately labeled using all four fluorochromes. Large
      tumors were labeled well only by Cy7, probably due to self-masking and dilution
      effects. Cy7 was superior to other cyanine fluorochromes for visualizing
      structures located deep within the animal.

PMID- 9618049
TI  - Successful treatment of accelerated and blastic phase of chronic myeloid leukemia
      with high-dose interferon-alpha combined with hydroxyurea.
AB  - Transformed chronic myeloid leukemia (CML) has a dismal prognosis, and treatment
      with a variety of chemotherapeutic agents is extremely disappointing. A novel
      therapeutic approach was initiated to improve the outcome of this condition. Nine
      patients, four females and five males, with either acceleration of CML or blast
      crisis (myeloid), or, in two instances, both, entered this pilot study. Median
      age was 60 years; seven patients were Philadelphia chromosome positive; two were
      negative but showed a bcr/abl rearrangement. All patients had a well-defined
      preceding period of stable chronic phase, for which they received sequentially
      hydroxyurea (N = 9), interferon (IFN) (N = 3), busulfan (N = 2), melphalan (N =
      1), 6-MP (N = 1), or allogeneic BMT (N = 1). Median length of preceding chronic
      phase to acceleration or blast crisis was 56 months. All patients responded to
      treatment with a starting dose of IFN (9 Mio U/day), subcutaneously, and
      hydroxyurea (3 g/day), orally, by reversal to chronic phase. Three of the
      patients responded repeatedly during their course of disease. Median time for
      reversal to chronic phase was 4 weeks. Adverse side effects like nausea,
      vomiting, hair loss, fever, and prolonged cytopenia as seen after chemotherapy
      were not observed. The duration of chronic phase varied, and lasted, in six
      instances, more than 5 months, while the Philadelphia chromosome persisted. One
      additional patient received an unrelated bone marrow transplantation after
      reaching chronic phase (+24 months). Disease progression occurred 2 months after
      cessation of treatment. This treatment has proven very promising so far.

PMID- 9618050
TI  - The outcome of liver transplantation at various times (70, 120, and 134 days)
      after the initiation of carcinogenesis in rats.
AB  - The therapeutic results of liver transplantation for primary liver cancer have
      not been satisfactory. The high rate of recurrence appears to be due to the
      inadequate care taken in selecting the most appropriate candidates for orthotopic
      liver transplantation (OLT), the presence of circulating hepatocellular carcinoma
      (HCC) cells and micrometastases at the time of liver transplantation, and the
      tumor growth-promoting effects of immunosuppressive agents. We believe that HCC
      patients must be carefully staged in order to identify those most suitable for
      OLT. We therefore induced HCC in pure-strain rats by the oral administration of
      diethylnitrosamine (DEN) and studied the outcomes of liver transplantation at
      various time points (70, 120, and 134 days) after the initiation of
      carcinogenesis. The mean survival time (MST +/- SD) of the non-OLT control group
      (N = 14) was 18.2 +/- 5 days after Day 120. The survival time of the four rats in
      the OLT Day 120 group was 81.3 +/- 20.6 days after transplantation. One rat
      showing full weight recovery soon after transplantation survived for 97 days
      after transplantation and then succumbed to recurrence. The survival time of the
      four rats in the OLT Day 134 group was 7.3 +/- 5.0 days after transplantation.
      The survival time of the three rats in the OLT Day 70 group was 145.3 +/- 70.0
      days after transplantation, with a maximum survival of 221 days until death.
      Significantly prolonged survival, as compared with that in the non-OLT group, was
      observed in the OLT Day 70 and OLT Day 120 groups (p < 0.01), while there was no
      significant prolongation in the OLT Day 134 group (NS). The timing of liver
      transplantation is a very important factor. Preoperative assessment of factors
      potentially affecting recurrence in HCC patients is imperative for selecting the
      most appropriate candidates for OLT. Careful selection of candidates for OLT
      should always be considered the key to successful liver transplantation (i.e.,
      long-term survival) for patients with liver cancer.

PMID- 9618051
TI  - Growth hormone, insulin-like growth factor-I and insulin-like growth factor
      binding protein-3 are regulated differently in small-for-gestational-age and
      appropriate-for-gestational-age neonates.
AB  - Growth hormone (GH), insulin-like growth factor-I (IGF-I) and IGF-binding protein
      3 (IGFBP-3) were measured in 90 neonates during the first 5 days of life. Twenty
      six small-for-gestational-age (SGA) neonates were compared with 64 appropriate
      for-gestational-age (AGA) neonates. There were no differences in nutritional
      status between the 2 groups. Mean GH levels were significantly higher in the SGA
      group (53.4 +/- 30.8 vs. 39.9 +/- 23.3 microg/l; p < 0.05). In both groups GH
      levels correlated with birth weight (expressed as SDS) but not with gestational
      age. IGF-I levels were significantly lower in SGA neonates (6.6 +/- 4.0 vs. 11.7
      +/- 8.2 ng/ml; p < 0.01). In SGA neonates with short stature, IGF-I levels were
      lower and GH levels were higher than in normal stature SGA neonates. IGFBP-3
      levels were significantly lower in SGA neonates than in AGA neonates (0.72 +/-
      0.40 vs. 0.98 +/- 0.43 microg/l; p < 0.01). IGF-I and IGFBP-3 correlated with
      gestational age in AGA but not in SGA neonates and there was no correlation with
      birth weight in either group. Our data provide evidence for a graduation in the
      severity of impact of fetal 'malnutrition' on the somatotropic axis and on
      intrauterine growth. The most severe state (SGA with short stature) was
      associated with a GH-resistance syndrome, characterized by very low IGF-I levels
      and high GH levels.

PMID- 9618052
TI  - Are biochemical parameters of lung maturation from gastric, tracheal, and
      pharyngeal aspirates comparable?
AB  - Phospholipid parameters -- lecithin/sphingomyelin (L/S) ratio and palmitic
      acid/stearic acid (P/S) ratio -- of gastric (GA), pharyngeal (PA), and tracheal
      aspirates (TA) have often been used for estimation of lung maturation. However,
      it was not known whether values from different sources can be alternatively used.
      The study was performed to test whether P/S and L/S ratios in GA, PA, and TA are
      comparable. 11 GA, 30 PA, and 10 TA were obtained from infants within 10 min
      after birth. All infants were healthy, vaginally delivered with no respiratory
      distress, and had a gestational age > or = 34 weeks. Patterns of fatty acids were
      determined by gas chromatography and the L/S ratio by high-performance liquid
      chromatography. We found lower L/S ratios in GA (16.5 +/- 5.2) when compared with
      PA(39 +/- 16) or TA (41 +/- 15; p < 0.01); there were no differences between PA
      and TA. The P/S ratio was in the same range in PA and TA, but lower in GA. As
      compared with TA and PA, in GA the relative percentage of palmitic acid of all
      fatty acids was lower, the percentage of monounsaturated fatty acids, however,
      higher. We conclude that phospholipid parameters of lung maturation in PA and TA,
      but not in GA, can be alternatively used.

PMID- 9618053
TI  - Maternal and neonatal lead exposure in southern Italy.
AB  - We evaluated the blood lead levels in 159 pregnant women and in their healthy
      newborns at birth. The blood lead levels were higher in mothers as compared with
      neonates, with a linear correlation between maternal and neonatal levels. The
      blood lead levels were also higher in neonates as compared with infants aged 6-12
      months, and, besides, 2.5% of the newborns had blood lead levels > 10 microg/dl,
      the actual level of concern according to the Center for Disease Control. The
      study of blood and urinary lead levels during the 1st week of life showed a
      steady decrease of blood lead levels, together with increasing levels of urinary
      lead. The mechanism of renal elimination is important to avoid persistently high
      free blood lead levels, with possible deposition in tissues with high lead
      affinity, such as bone. In newborns, the possibility of a functional renal
      insufficiency during the first days of life suggests that newborns with high cord
      blood lead levels and impaired renal function could be at high risk of lead
      toxicity, so that it could be advisable to perform a careful and prolonged follow
      up.

PMID- 9618054
TI  - Value of myocardial hypoxia markers (creatine kinase and its MB-fraction,
      troponin-T, QT-intervals) and serum creatinine for the retrospective diagnosis of
      perinatal asphyxia.
AB  - Neonatal asphyxia is a major topic of neonatal research. However, no clear-cut
      physiologic parameters exist which enable an early identification of neonatal
      infants who are either at risk to develop brain damage or posthypoxic heart
      failure. Parameters indicating dysfunction of the heart and kidneys as creatinine
      and creatinine kinase have been evaluated. In our study, 47 asphyxiated infants
      (umbilical artery pH < 7.18 and either a 1-min Apgar score < 4 or a 5-min Apgar
      score < 7) were compared to 27 nonasphyxiated controls regarding significant
      differences in creatinine, creatinine kinase, its MB fraction, and a newly
      introduced myocardial hypoxia indicator -- troponin T -- to establish the value
      of these parameters in the retrospective diagnosis of asphyxia. Further we
      evaluated two subsets of these 47 asphyxiated infants with either subsequent
      signs of encephalopathy (seizures) or heart failure. Creatinine, creatinine
      kinase and troponin T were significantly elevated in asphyxiated infants compared
      with controls; no differences were found in creatinine kinase and its MB
      fraction. In asphyxiated infants with heart failure, troponin T was significantly
      higher than in the other asphyxiated infants. However, none of the parameters
      studied was significantly different in patients with brain damage compared with
      asphyxiated infants without neurological sequelae. Troponin T has a high positive
      predictive value in the postnatal diagnosis of asphyxia. The diagnostic power of
      troponin T equals that of creatinine. However, troponin T is more sensitive in
      the identification of infants with asphyxia and cardiocirculatory failure than
      creatinine. Creatinine kinase and its MB fraction have no diagnostic value.

PMID- 9618055
TI  - Maturation of glucose-stimulated insulin secretion in fetal sheep.
AB  - To determine the gestational maturation of fetal insulin response to glucose and
      arginine and the effects of sustained hyperglycemia on these processes, we
      measured insulin secretion in different groups of fetal sheep at 75, 100, 122,
      and 137 days of gestation (50, 67, 81, and 91% of term gestation, respectively).
      The basal glucose concentration decreased progressively from 1.36 +/- 0.16 mM at
      75 days to 1.00 +/- 0.07 mM at 137 days (p < 0.05). The fetal plasma insulin
      concentration did not change (54 +/- 11 pM at 75 days, 68 +/- 8 pM at 137 days),
      but there was a significant increase in the increment in plasma insulin
      concentration in response to a hyperglycemic clamp over this same period (deltaI
      pM/deltaG mM) from 20 +/- 3 at 75 days to 105 +/- 8 at 137 days (p < 0.001). The
      deltaI (pM) in response to arginine also increased from 129 +/- 17 pM at 75 days
      to 635 +/- 103 pM at 137 days (p < 0.001). Sustained hyperglycemia from 90 to 100
      days reduced the deltaI (pM)/deltaG (mM) to glucose (13 +/- 2, p < 0.01) and the
      deltaI pM to arginine (369 +/- 86, p < 0.05) to values less than those found in
      euglycemic animals (deltaI/deltaG = 58 +/- 4 to glucose, deltaI = 525 +/- 71 to
      arginine). Thus, glucose and arginine stimulate insulin secretion at midgestation
      at 20% of the rate near term, and there is a consistently positive developmental
      pattern of insulin secretion to these secretagogues over the second half of
      gestation. Furthermore, chronic, high, relatively constant hyperglycemia blunts
      insulin secretion to glucose and arginine close to midgestation, similar to the
      effect seen near term. Such developmental and adaptive capacities may account for
      an important part of the variability in fetal glucose metabolism observed in
      animal models and human cases of diabetes during pregnancy.

PMID- 9618056
TI  - Effect of L-aspartate on the ventilatory response to hypoxia in sedated newborn
      piglets.
AB  - L-aspartate (L-ASP) acts as an excitatory amino acid neurotransmitter at the
      synapses of brain stem respiratory neurons. In order to determine the effect of L
      ASP on the neonatal ventilatory response to hypoxia, 9 control piglets [age 4.3
      +/- (SD) 0.9 days, weight 1.9 +/- 0.5 kg] and 9 L-ASP-treated animals [age 5.0 +/
      (SD) 1.4 days, weight 2.1 +/- 0.7 kg] were studied. Minute ventilation, oxygen
      consumption, arterial blood pressure, and blood gases were measured in sedated
      piglets while spontaneously breathing room air and during 1, 5, and 10 min of
      hypoxia (O2 concentration in inspired gas 0.10). Measurements were obtained
      before and 60 min after the administration of L-ASP (580 mg/kg i.v. over 1 h) or
      5% dextrose solution. In the control animals, the ventilatory response to hypoxia
      was similar before and after dextrose infusion. In contrast, a significant and
      sustained increase in ventilation was observed at 1, 5, and 10 min of hypoxia
      after the administration of L-ASP. Changes in oxygen consumption, heart rate,
      arterial blood pressure, pH, and arterial O2 tension with hypoxia were similar
      before and after the L-ASP infusion, while the arterial CO2 tension decreased
      significantly during hypoxia after the administration of L-ASP. These data
      suggest that the excitatory amino acid L-ASP is an important mediator of the
      hypoxic hyperventilation in the neonate. We speculate that the administration of
      exogenous L-ASP modifies the balance of central nervous system neurotransmitters
      during hypoxia, resulting in predominance of excitatory neurotransmission.

PMID- 9618057
TI  - Effects of prenatal maternal TRH stimulation on the postnatal ability of neonatal
      piglets to cope with a cold challenge.
AB  - The effect of administering thyrotropin-releasing hormone (TRH) before farrowing
      on the ability of their newborn piglets to withstand a cold challenge was
      studied. Sows received intravenous infusions of TRH (5 microg kg(-1); TRH group)
      or physiological saline (0.9% NaCl; control group) from day 105 of gestation
      until farrowing. The plasma concentrations of thyroxine and triiodothyronine
      increased in sows treated with TRH. There were no differences in thyroxine and
      triiodothyronine between pigs born to sows in the TRH group and those of the
      control group. The rectal temperature of piglets born to TRH-treated sows
      decreased less than that of piglets born to controls as a consequence of a 1-hour
      cold challenge. Piglets born to sows in the TRH group had higher body weights at
      birth, and by day 28 they were an average 600 g heavier than those born to sows
      in the control group. Summarizing, prenatal maternal treatment with TRH appears
      to increase piglets' resistance to cold as well as to have beneficial effects on
      birth and weaning weights.

PMID- 9618058
TI  - Insulin-like growth factor binding protein 1 level in amniotic fluid: correlation
      with birth weight.
AB  - Insulin-like growth factor binding protein 1 is the predominant insulin-like
      growth factor binding protein in amniotic fluid. It is produced by the decidua
      and by fetal tissues, and it is thought to play an important role in fetal
      growth. We have measured this protein in 58 samples of amniotic fluid, from 13 to
      19 gestational weeks, and found a highly significant negative correlation with
      fetal weight at birth. We conclude that the level of insulin-like growth factor
      binding protein 1 in amniotic fluid at midpregnancy is a good marker of fetal
      growth failure.

PMID- 9618059
TI  - Effect of alpha-gene numbers on the expression of beta-thalassemia intermedia,
      beta-thalassemia and (delta beta)0-thalassemia traits.
AB  - The effects of variations in alpha-gene numbers on phenotypical expression of
      beta-thalassemia are assessed in 11 subjects of 8 families. The study indicates
      that coexistence of alpha-thalassemia (-alpha3.7/alpha alpha) decreases the HbF
      in IVSI-6 homozygote and in delta beta thalassemia trait and may ameliorate the
      disease in beta-thalassemia compound heterozygotes associated with one mild and
      one severe beta-thalassemia mutation. Coexistence of alpha-gene triplication is
      associated with an increase in HbF value and may increase the severity of beta
      trait or beta-thalassemia intermedia. The effects of alpha-gene triplication on
      phenotypic expression of beta-thalassemia trait may not be uniformly observed in
      every subject affected with a similar genotype.

PMID- 9618060
TI  - Genetic relationships among Japanese, northern Han, Hui, Uygur, Kazakh, Greek,
      Saudi Arabian, and Italian populations based on allelic frequencies at four VNTR
      (D1S80, D4S43, COL2A1, D17S5) and one STR (ACTBP2) loci.
AB  - The genetic polymorphism at four variable number of tandem repeats (D1S80, D4S43,
      COL2A1, D17S5) and one short tandem repeat (ACTBP2) loci was assessed by
      polymerase chain reaction analysis of genomic DNA obtained from blood samples of
      eight human populations (Japanese, Northern Han, Hui, Uygur, Kazakh, Saudi
      Arabian, Greek, Italian). Allele frequencies at all loci were in the Hardy
      Weinberg equilibrium for each population. With the exception of ACTBP2, the
      allelic distribution patterns for these loci revealed a marked genetic divergence
      among the eight populations. A dendrogram constructed by the neighbor-joining
      method based on the allele frequencies of the five loci suggested that the five
      Asian populations (Japanese, Northern Han, Hui, Uygur, and Kazakh) formed one
      cluster, whereas the two European populations and one West Asian population
      (Italian, Greek, and Saudi Arabian) formed another. The genetic relationship
      among these populations may have been greatly influenced by admixture as a result
      of the migration of individuals along the Silk Road throughout history.

PMID- 9618062
TI  - The genetic polymorphism of aminolevulinate dehydratase (ALADH) in Greece.
AB  - The distribution of phenotypic and allelic frequencies of aminolevulinate
      dehydratase (ALADH) in different areas of Greece is reported. The frequencies of
      the allele ALADH1 and ALADH2 in Greece are 0.955 and 0.0455, respectively.

PMID- 9618061
TI  - Mapping genes through the use of linkage disequilibrium generated by genetic
      drift: 'drift mapping' in small populations with no demographic expansion.
AB  - Linkage disequilibrium has been a powerful tool in identifying rare disease
      alleles in human populations. To date, most research has been directed to
      isolated populations which have undergone a bottleneck followed by rapid
      exponential expansion. While this strategy works well for rare diseases in which
      all disease alleles in the population today are clonal copies of some common
      ancestral allele, for common disease genes with substantial allelic
      heterogeneity, this approach is not predicted to work. In this paper, we describe
      the dynamics of linkage disequilibrium in populations which have not undergone a
      demographic expansion. In these populations, it is shown that genetic drift
      creates disequilibrium over time, while in expanded populations, the
      disequilibrium decays with time. We propose that common disease alleles might be
      more efficiently identified by drift mapping - linkage disequilibrium mapping in
      small, old populations of constant size where the disequilibrium is the result of
      genetic drift, not founder effect. Theoretical models, empirical data, and
      simulated population models are presented as evidence for the utility of this
      approach.

PMID- 9618063
TI  - Phenotypic variability in five cystic fibrosis patients compound heterozygous for
      the Y1092X mutation.
AB  - Five cystic fibrosis (CF) patients distributed in three families and compound
      heterozygotes for the Y1092X mutation have been followed for a period ranging
      from 5 to 20 years. The genealogical reconstruction identified a common ancestor
      couple to all 3 families at the 5th generation. All 5 patients were pancreatic
      insufficient. A high variability in the clinical aspects and pulmonary function
      was seen between the families, but not within. Based on our observations, it will
      be very difficult to predict the course of disease for CF patients with the
      Y1092X mutation, even if they are closely related (first-degree cousins).

PMID- 9618064
TI  - The Awa-Guaja Indians of the Brazilian Amazon. Demographic data, serum protein
      markers and blood groups.
AB  - The South-American Indian group Awa-Guaja, currently living in the State of
      Maranhao (Northeastern Brazil), is one of the most recently contacted Indian
      groups of the Brazilian Amazon. This group is made up by three partially isolated
      villages named Awa, Guaja and Juriti, and is characterized by having a young
      population, in which 47.6% of the individuals range from 0 to 14 years old. The
      sex ratios (male/female) for people of reproductive age are 1.13 for Awa village,
      2.00 for Guaja, 3.33 for Juriti and 1.61 for the tribe as a whole. Fst and
      heterogeneity analysis show that, despite the small differences observed among
      villages for the eight genetic systems analyzed, the Awa-Guaja tribe is
      constituted of only one population. Furthermore, comparisons between Awa-Guaja
      and Urubu-Kaapor tribes indicate that they are still isolated genetically, in
      spite of the fact that they share territories.

PMID- 9618065
TI  - Clinical heterogeneity of familial spastic paraplegia linked to chromosome 2p21.
AB  - The clinical features of four families with autosomal dominant spastic
      paraparesis (FSP) are described, along with the results of linkage analysis to
      markers from the regions of chromosomes 2, 14, and 15 which are known to contain
      spastic paraplegia genes. All families had 'pure' spastic paraparesis (FSP), but
      the severity of symptoms varied widely among families, and other mild neurologic
      signs were observed in some subjects. Although no family individually yielded a
      lod score >3.0, all families yielded positive lod scores with chromosome 2
      markers, and a maximal lod score of 5.7 was obtained for the families combined
      using marker D2S352. There was no evidence of linkage to chromosome 14 or 15 in
      any of the families.

PMID- 9618067
TI  - Observations on severe ulnar neuropathy in diabetes.
AB  - We describe the clinical and neurophysiologic findings in a group of diabetic
      patients with a severe ulnar neuropathy. All patients attending a large inner
      city diabetes center were prospectively screening for hand wasting and weakness
      due to ulnar nerve disease. Twenty diabetic patients fulfilling the clinical
      criteria underwent nerve conduction studies and electromyography. All but one
      patient with a motor ulnar neuropathy had systemic complications, mostly severe:
      ten were amputees, four had had a renal transplant, and two were blind. The onset
      of hand weakness was sudden in five. All patients had a classical "ulnar hand"
      (bilateral in five) but forearm muscles were little affected. Sensory loss was
      prominent in only one-half. Nerve conduction studies showed markedly reduced
      ulnar motor responses (mean, 1.2 mV versus 7.4 mV in controls) and ulnar/median
      motor ratios. Motor conduction was disproportionately slowed across the elbows,
      with or without conduction block, in only eight of 34 affected ulnar nerves. Five
      of these patients had a habit of leaning on their elbows and/or a Tinel's sign.
      Median sensory action potentials (SAPs) were recordable in 12 patients but ulnar
      SAPs were absent in 30 of 34 affected nerves. Electromyography revealed advanced
      denervation of ulnar supplied hand muscles. We conclude that motor ulnar
      neuropathy is not uncommon in patients with diabetes of long standing, especially
      in those with severe systemic complications. Nerve entrapment at the elbows
      occurs in some, but in many the lesion is axonal, and damage may occur through
      ischemia.

PMID- 9618066
TI  - Progression rates of diabetic neuropathy in placebo patients in an 18-month
      clinical trial. Ponalrestat Study Group.
AB  - Recent clinical drug trials designed to test the effect on established mild
      diabetic neuropathy have in general been disappointing. These findings may in
      part be due to a failure of tested drugs to reverse neuropathy (they may merely
      halt its progression) and to insufficient durations of the trials. To aid the
      design of future studies, we examined the progression rates of quantitative
      sensory tests, autonomic functions, and sensory and motor nerve electrophysiology
      in 182 patients designed to placebo treatment in an 18-month multicenter ARI
      trial. Clinically meaningful deteriorations were demonstrated in the vibratory
      perception threshold in the toe and the Valsalva ratio. The greatest
      deterioration rate in electrophysiologic measures was found in peroneal F-wave
      latency and in sensory nerve conduction velocities in the upper limb, but none of
      these reached the threshold of clinically meaningful change. Assuming that drug
      efficacy will be based on the deterioration rates in placebo patients alone, the
      present data suggest a minimum of 250 patients treated for at least 2 years to
      achieve convincing efficacy.

PMID- 9618068
TI  - Prospective bone mineral density evaluation in patients with insulin-dependent
      diabetes mellitus.
AB  - The bone mineral density (BMD) in patients with insulin-dependent diabetes
      mellitus (IDDM) was evaluated prospectively to assess the course of osteopenia in
      IDDM. We measured BMD in the lumbar spine, femoral region, and total body calcium
      in 23 patients aged 21-53 years with IDDM for 2.3 to 20 years using a dual energy
      X-ray absorptiometry. A second BMD measurement was done after 26.5+/-4.1 months
      in all patients. The blood glucose control, insulin dosage, and disease duration
      were also assessed. Eleven patients had osteopenia (1 Z-score below the mean
      values of normal gender- and age-matched individuals). These patients had a
      longer IDDM duration (8.6+/-5.1 years in osteopenics versus 4.6+/-3.75 years in
      non-osteopenics; p=0.03). The blood glucose control and insulin dosage were not
      significantly different throughout the study. The mean spinal BMD was higher in
      the second evaluation in both osteopenics (0.91+/-0.12 g/cm2 and 0.96+/-0.09
      g/cm2, p=0.035) and non-osteopenics (1.24+/-0.15 g/cm2 and 1.29+/-0.16 g/cm2;
      p=0.02). In the end of the study, however, the osteopenic group persisted with
      lower subnormal BMD values than the non-osteopenic group (p < 0.001). The small
      BMD increment observed in the spine did not correlate with changes in the
      metabolic control or with IDDM duration, but occurred mainly in patients younger
      than 30 years old. There was no significant change in the femoral BMD or total
      body calcium. None of the patients developed or significantly worsened the
      osteopenia. We conclude that diabetic osteopenia, despite being a complication of
      high prevalence in IDDM, seems to be non-progressive in the majority of patients.
      In some patients, the spinal BMD increased during observation and may have been
      due to achievement of peak bone mass.

PMID- 9618069
TI  - Lack of relationship between sympathetic nervous system activity, measured by two
      circulating markers, and blood pressure in diabetic and nondiabetic subjects.
AB  - Two putative sympathetic nervous system (SNS) markers, noradrenaline and
      neuropeptide Y (NPY) were related to 24-h ambulatory blood pressure (BP) in 59
      normotensive subjects, 34 non-insulin-dependent diabetics, and 25 controls.
      Plasma NPY levels were not significantly different between the two groups [non
      insulin-dependent (NIDDM) diabetes mellitus 4.33 (3.25-5.78), controls 5.68 (3.39
      6.97) p=0.26] as were those of noradrenaline (1.51+/-0.69 versus 1.78+/-0.55;
      p=0.053). There were correlations, controlled for age and obesity, of plasma NPY
      with clinic and night time diastolic BP in the control group only (r=0.49
      [p=0.013] and r=0.48 [p=0.023] respectively). No similar correlation was found in
      the NIDDM group, or between plasma noradrenaline and blood pressure in either
      group. No correlation was found between plasma insulin and NPY or noradrenaline
      levels. There is a weak independent relationship between NPY and blood pressure
      in normotensive nondiabetics but not in NIDDM subjects. We found no evidence for
      the hypothesis that insulin modulates blood pressure through activity of the SNS.

PMID- 9618070
TI  - Normal blood flow response and vasomotion in the diabetic Charcot foot.
AB  - Vasomotion, the spontaneous rhythmic contraction exhibited by small arteries and
      arterioles is dysregulated in patients with diabetic neuropathy. We examined the
      relationship between Charcot arthropathy and vasomotion at the dorsum of the
      foot. We studied nine diabetic patients with clinically diagnosed neuropathy and
      Charcot arthropathy in 13 feet (n=13), twelve subjects with diabetic neuropathy
      and no Charcot deformity (n=12), and 11 healthy controls (n=11). Following
      neuropathy assessment, blood flow was measured by laser Doppler flowmetry with
      local skin warming. Fast Fourier transformation was performed to provide an index
      of vasomotion. Subjects with Charcot osteoarthropathy had more severe somatic
      neuropathy and higher circulating levels of serum calcium (9.8+/-0.1 versus 9.3+/
      0.1 mg/dL). Raising local temperature increased skin blood flow and vasomotion in
      both control subjects and Charcot subjects, but not in diabetic patients with
      neuropathy alone (p < 0.05 for blood flow, p < 0.02 for vasomotion). Patterns of
      peripheral vasomotion and blood flow which are clearly disordered in diabetic
      neuropathy are intact in patients with a Charcot osteoarthropathy, despite a more
      severe sensory nerve impairment. These findings suggest that the loss of
      peripheral blood flow and vasomotion often seen in diabetic neuropathy may
      actually be protective against Charcot arthropathy by preventing bone resorption.
      It remains unclear then whether the Charcot arthropathy is a direct result of a
      failure to decrease blood flow to bone, or is the manifestation of some other
      pathology.

PMID- 9618072
TI  - Effect of SG-210, a novel aldose reductase inhibitor, on impaired polyol pathway
      in rats received diabetic manipulations.
AB  - To investigate the effect of SG-210, a potent inhibitor selective to aldose
      reductase (ARI), on the impaired polyol pathway, we examined biochemically and
      histologically the potencies of this compound in streptozotocin-induced diabetic
      or galactosemic rats. The study with diabetic rats showed that SG-210 (1-10 mg x
      kg(-1)) dose-dependently inhibited sorbitol accumulations in erythrocytes,
      sciatic nerves, lens, and retina with ED50 values of 1.4, 1.3, 3.5, and 4.6 mg x
      kg(-1), respectively. Zenarestat, currently under clinical trials both in Japan
      and the United States, was about two or over five times less potent than SG-210
      in suppressing sorbitol contents of erythrocytes or other tissues, respectively.
      Epalrestat, commercially available, was much less potent in reducing the contents
      with ED50 values of more than 30 mg x kg(-1) in all of the cells and the tissues
      examined. An extensive study using galactosemic rats indicated that SG-210 (3-30
      mg x kg(-1)) inhibited galactitol accumulations in lens and retina as well as in
      erythrocytes, preventing the progression of histological abnormalities in lens
      accompanied by the reduction in galactitol contents. Epalrestat (3-30 mg x kg(
      1)) failed to show any significant effects. Pharmacokinetic studies suggested
      that SG-210 has a high bioavailability and possesses a long half-life in rats
      (ca. 10 h). Taken together with its excellent pharmacokinetic profiles, the
      potent suppressive effects of SG-210 observed in this study may be available as a
      new treatment of diabetic complications.

PMID- 9618071
TI  - Effect of the aldose reductase inhibitor tolrestat on nerve conduction velocity,
      Na/K ATPase activity, and polyols in red blood cells, sciatic nerve, kidney
      cortex, and kidney medulla of diabetic rats.
AB  - Long-term prospective studies comparing the effects of conventional and intensive
      insulin therapy have linked diabetic hyperglycemia to the development of diabetic
      retinopathy, nephropathy, and neuropathy. The mechanisms through which glucose
      metabolism leads to the development of these secondary complications, however,
      are incompletely understood. In animal models of diabetic neuropathy, the loss of
      nerve function in myelinated nerve fibers has been related to a series of
      biochemical changes. Nerve glucose, which is in equilibrium with plasma glucose
      levels, rapidly increases during diabetic hyperglycemia because glucose entry is
      independent of insulin. This excess glucose is metabolized in large part by the
      polyol pathway. Increased flux through this pathway is accompanied by the
      depletion of myo-inositol, a loss of Na/K ATPase activity and the accumulation of
      sodium. Supportive evidence linking these biochemical changes to the loss of
      nerve function has come from studies in which aldose reductase inhibitors block
      polyol pathway activity, prevent the depletion of myo-inositol and the
      accumulation of sodium and preserve Na/K ATPase activity, as well as nerve
      function. The kidney and red blood cells (RBCs) are two additional sites of
      diabetic lesions that have been reported to develop biochemical changes similar
      to those in the nerve. We observed that polyol levels in the kidney cortex,
      medulla, and RBCs increased two- to ninefold in rats following 10 weeks of
      untreated diabetes. Polyol accumulation was accompanied by a 30% decrease in myo
      inositol levels in the kidney cortex, but no change in RBCs or the kidney
      medulla. Na/K ATPase activity was decreased by 59% in RBCs but was unaffected in
      the kidney cortex or medulla. Aldose reductase inhibitor treatment that preserved
      myo-inositol levels, Na/K ATPase, and conduction velocity in the sciatic nerve
      also preserved Na/K ATPase activity in RBCs. Our results suggest that the
      pathophysiologic mechanisms underlying diabetic neuropathy are different from
      those of diabetic nephropathy. Our results also suggest that RBCs maybe a
      surrogate tissue for the assessment of diabetes-induced changes in nerve Na/K
      ATPase activity.

PMID- 9618073
TI  - Protective effects of a small dose of captopril on the reduction of glomerular
      basement membrane anionic sites in spontaneously hypertensive rats with
      streptozotocin-induced diabetes.
AB  - Angiotensin-converting enzyme (ACE) inhibitors have been used in several clinical
      trials to slow a progressive decline in glomerular function in patients with
      diabetic nephropathy independent of their effects on blood pressure. The purpose
      of this study was to clarify the mechanisms(s) through which an ACE inhibitor,
      captopril, exerts its protective effect on renal function using spontaneously
      hypertensive rats (SHR) with streptozotocin (STZ)-induced diabetes. Male SHRs
      were made diabetic by intravenous injection of STZ (45 mg/kg). One hundred or 25
      mg/kg of captopril was administered daily for 4 weeks to them. Urine albumin
      excretion (UAE) rate was markedly increased in diabetic SHRs, while captopril
      treatment resulted in a significant suppression of UAE in diabetic SHRs,
      independent of both its daily dose and effects on blood pressure as well as
      glycemic control. Examination by electron microscope revealed that the number of
      anionic sites (AS) in the lamina rara externa per 1000 nm of glomerular basement
      membrane (GBM) was significantly decreased (22.9+/-0.2 to 16.1+/-0.3, p < 0.001),
      after induction of diabetes, whereas, significant recovery (18.2+/-0.1, p <
      0.001) could be obtained even by the smaller dose (25 mg/kg) of captopril which
      did not exert either antihypertensive or antidiabetic effect on diabetic SHRs.
      Thus, we demonstrate here the direct evidence that captopril, an ACE inhibitor,
      can protect against damage on GBM of diabetic SHR without controlling blood
      pressure as well as blood glucose level.

PMID- 9618074
TI  - Circulating levels of tartrate-resistant acid phosphatase in rat models of non
      insulin-dependent diabetes mellitus.
AB  - In order to investigate the pathogenic role of bone resorption by osteoclasts in
      altered bone metabolism in non-insulin-dependent diabetes mellitus (NIDDM), the
      circulating levels of tartrate resistant acid phosphatase (TRACP) were
      simultaneously determined with osteocalcin, in rat models of NIDDM, i.e., genetic
      Wistar fatty rats and neonatally streptozotocin-induced diabetic rats (NSZ rats).
      In Wistar fatty rats exhibiting hyperglycemia and hyperinsulinemia, plasma TRACP
      was 40.0+/-0.4 U/l (mean+/-SE), significantly higher than that of 32.8+/-1.3 U/l
      in their lean littermates (p < 0.01). Bone length, bone strength, and weight of
      powdered bone in Wistar fatty rats were significantly decreased compared to
      control rats (p < 0.02-0.001). On the other hand, plasma TRACP in NSZ rats was
      13.6+/-1.0 U/l, significantly lower than that of 31.4+/-1.2 U/l in their controls
      (p < 0.01). In addition, there were positive correlations between circulating
      TRACP and insulin levels in both NIDDM rat models (p < 0.05-0.01). Furthermore,
      plasma osteocalcin levels in these NIDDM models were significantly decreased than
      those of their corresponding controls (p < 0.001). Consequently, in Wistar fatty
      rats with hyperinsulinemia, it is suggested that the bone formation by
      osteoblasts was decreased, while the bone resorption by osteoclasts was
      increased. In contrast, in NSZ rats with hypoinsulinemia, both of bone formation
      and resorption were speculated to be decreased, indicating the decreased bone
      turnover. These results suggest that, although the deterioration in the
      osteoblastic function can be commonly observed in NIDDM animal models, the
      osteoclastic function is heterogeneous under NIDDM conditions.

PMID- 9618075
TI  - HIV type 1-reactive chemokine-producing CD8+ and CD4+ cells expanded from
      infected lymph nodes.
AB  - The chemokines RANTES, MIP-1alpha, and MIP-1beta have been identified as HIV-1
      suppressive factors produced by CD8+ T cells. We examined the possibility that
      HIV-1-specific, chemokine-releasing T cells could be expanded from the lymph
      nodes of patients with advanced infection. Lymphocytes, separated from lymph
      nodes of patients with peripheral blood CD4 counts less than 500/microl obtained
      at diagnostic biopsies, were activated with anti-CD3 monoclonal antibody, and
      cultured in vitro for up to 12 days with IL-2. The phenotype, proliferative
      response, chemokine production, and anti-HIV-1 activity of the expanded cells was
      examined. Cells expanded 2.4- to 49-fold from patients with as few as 15 CD4+
      cells/microl in their peripheral blood. Expanded cells were a mixture of
      CD8+CD45RO+ and CD4+CD45RO+ T cells. The CD8+ cells were also CD30+CDw60+CD11b-.
      When challenged with autologous B cell targets expressing HIV-1 Env protein,
      unseparated expanded cells, and purified CD8+ and CD4+ T cell subsets,
      proliferated and secreted MIP-1alpha and RANTES. Expanded cells were negative for
      HIV-1 by PCR and by culture. Culture supernatants inhibited the replication of
      HIV-1 in CD4+ cells in vitro. These studies indicate that HIV-1 can stimulate
      chemokine release by CD8+ and CD4+ cells expanded from infected lymph nodes, even
      from individuals with advanced infection. The numbers of chemokine-releasing T
      cells produced in these short-term cultures may be sufficient to be applied
      therapeutically as an autologous cellular therapy for HIV-1.

PMID- 9618076
TI  - Hematologic and virologic effects of lineage-specific and non-lineage-specific
      recombinant human and rhesus cytokines in a cohort of SIVmac239-infected
      macaques.
AB  - The hematologic abnormalities of SIV and HIV are well described, although the
      mechanisms that lead to hematopoietic dysfunction are yet to be fully defined. A
      number of growth factors and cytokines have been used to induce the
      differentiation, maturation, and proliferation of appropriate lineages, with the
      aim that such therapy will lead to functional hematopoietic reconstitution.
      Within this context, some cytokines have been shown to influence HIV and SIV
      replication in vitro and, in selected cases, in vivo. However, few studies detail
      the effects of hematopoietic cytokines such as IL-3, Flt-3 ligand, G-CSF, Tpo,
      and Epo or correlate the effects on virus replication. In an effort to address
      this issue, we infected 12 rhesus macaques with 500 TCID50 of SIVmac239 and
      intensively evaluated hematologic, virologic, and immunologic parameters during
      administration of cytokines. When all animals had lymphadenopathy,
      hepatosplenomegaly, and CD4+ cell counts > or =1000/microl, subgroups of three
      rhesus macaques were administered either rhFlt-3; rrIL-3a; combination of rhG
      CSF, rhTpo, and rhEpo (rhGET); or rrIL-12. Fourteen days of rhFlt-3
      administration induced expansion of the bone marrow CD34+ cells and granulocyte
      macrophage colony-forming units (GM-CFUs) and increased absolute peripheral blood
      CD34+ cells and total CFUs. Following rrIL-3 and rhGET administration absolute
      peripheral blood CD34+ cells and total CFUs increased. rhGET also increased
      granulocyte, platelet, and reticulocyte counts by day 14 of administration.
      Branched DNA and coculture assays did not demonstrate any significant change in
      viral load with any of the cytokines administered. These data suggest that SIV
      infected rhesus macaques have the hematopoietic capability to expand and mobilize
      CD34+ and GM-CFU progenitors and formed elements at 6-8 months postinfection in
      response to various cytokines, without increasing viral load.

PMID- 9618077
TI  - A longitudinal study of seroreactivity against Mycoplasma penetrans in HIV
      infected homosexual men: association with disease progression.
AB  - We investigated the relationships between a putative cofactor of HIV infection,
      Mycoplasma penetrans, and the evolution of HIV disease. The evolution of titers
      of anti-M. penetrans antibodies in 58 randomly selected HIV-seropositive adult
      homosexual men was investigated. The median length of follow-up was 38 months.
      Thirty-six individuals was investigated. The median length of follow-up was 38
      months. Thirty-six individuals (62.1%) remained M. penetrans seronegative (group
      0). Fourteen patients (24.1%) had consistently low antibody titers or low
      antibody titer(s) in at least one sample and negative test(s) in the other(s).
      This pattern was possibly associated with latent or earlier infection (group 1).
      Eight patients (13.8%) had moderate to high antibody titers for long periods,
      indicating an active and persistent M. penetrans infection (group 2); four
      patients in this group presented a serological reactivation and thus probably
      developed an acute infection during the study; two had a stable and moderate
      level of antibody throughout the study; in two patients the antibody titers
      decreased substantially. Interestingly, CD4 cell counts declined more rapidly in
      group 2 than in group 0 (medians of -4.5 versus -2.1 cells/mm3/month, p < 0.05
      and -0.16 versus 0 cell percentage/month, p < 0.05), whereas there was no
      significant difference between groups 1 and 0 (medians of -2.0 versus -2.1
      cells/mm3/month and -0.15 versus 0 cell percentage/month). In patients with
      serological reactivation, the viral load was higher in sera with higher M.
      penetrans antibody titers. These findings suggest an association between active
      M. penetrans infection and progression of HIV disease.

PMID- 9618078
TI  - A sudden epidemic of HIV type 1 among injecting drug users in the former Soviet
      Union: identification of subtype A, subtype B, and novel gagA/envB recombinants.
AB  - The former Soviet Union republics have experienced an explosive human
      immunodeficiency virus type 1 (HIV-1) epidemic among injecting drug users (IDUs),
      consisting mainly of subtype A viruses originated from a point source (Bobkov et
      al.: AIDS Res Hum Retroviruses 1997;13:1195-1201). To determine whether new HIV-1
      subtypes have entered the IDU population, 46 samples derived from IDUs in Russia
      (n = 39) and the Ukraine (n = 7) were genotyped by heteroduplex mobility assay
      (HMA). It was shown that 83% of IDU HIV-1 strains found in both countries belong
      to genetic subtype A. However, env subtype B was also found in 17% of cases. The
      sequence data showed a marked intrasubtype homogeneity of HIV-1 (the average
      means of interpatient genetic distance were 1.1 and 1.7% [in the gag gene] or 1.8
      and 2.3% [in the env gene] for subtype A and subtype B, respectively), confirming
      the hypothesis of a point source of virus for each subtype variant. Moreover,
      recombinant gagA/envB variants originating from those two strains were also found
      in two samples collected in the Kaliningrad region of Russia. In conclusion, our
      results suggest that two strains of HIV-1 belonging to different genetic
      subtypes, A and B, as well as gagA/envB recombinants between genomes of these
      strains, are now circulating simultaneously among IDUs in the former Soviet
      Union.

PMID- 9618079
TI  - Genetic characterization of HIV type 1 from migrant workers in three South
      African gold mines.
AB  - The phylogenetic relationships between 44 HIV-1 isolates from 43 infected
      subjects employed by three adjacent South African gold mines were investigated.
      The patients were migrant workers originating from rural areas of South Africa
      and the neighboring countries of Lesotho, Botswana, Swaziland, and Mozambique.
      Proviral HIV-1 DNA was subtyped using a heteroduplex mobility assay (HMA) based
      on the 700-bp V3-V5 region of the env gene. DNA sequence analysis was used to
      confirm the subtype designation and to determine phylogenetic relationships
      between isolates. All 44 HIV-1 isolates were identified as env subtype C using
      both HMA and phylogenetic analysis. These isolates did not show a distinct
      phylogenetic relatedness based on the geographic origins of the migrant workers
      or show close homology to other subtype C sequences from southern Africa or
      India. However, five clusters of closely related sequences were identified,
      mainly involving miners of disparate geographic origins, suggesting possible
      epidemiological linkage in these few cases. The characteristic tetrapeptide
      sequence, GPGQ, at the tip of the V3 loop of subtype C viruses was conserved in
      the predicted amino acid sequences of most isolates. The heterogeneity of HIV-1
      sequences among migrant workers in a mining cohort suggests multiple
      introductions of HIV-1 subtype C into this population that are not apparently
      linked to the geographic origins of the patients.

PMID- 9618081
TI  - The development and evaluation of a probe hybridization method for subtyping HIV
      type 1 infection in Uganda.
AB  - We developed a method for large-scale screening of HIV-1 genotypic variation
      based on DNA probe hybridization. Nested PCR amplifications were performed to
      generate fragments in the env C2-V3 region and also in the gp41 region, which
      encompasses the immunodominant domain. The proviral DNA sequences were derived
      from 68 samples and phylogenetically analyzed. For comparison, the C2-V3 fragment
      was used in DNA probe hybridization to rapidly determine the infecting HIV
      subtype. The hybridizing probes were designed on the basis of the two most
      prevalent subtypes in Uganda, A and D. The results were compared to evaluate the
      feasibility of using this hybridization method for large-scale genotypic
      screening. Sequence analysis of the 68 amplified PCR fragments showed that 39
      were subtype A and 29 were subtype D. The results of DNA hybridization to the
      amplified products with A and D subtype-specific probes were more than 90%
      concordant with the subtypes determined by sequence analysis. Our findings
      suggest that probe hybridization with subtype-specific probes is effective for
      large-scale screening of HIV-infected populations. Application of this method
      will significantly reduce the time needed for large, population-based
      investigations.

PMID- 9618080
TI  - Genotypic characterization of human immunodeficiency virus type 1 in Greece.
      Multicentre Study on HIV-1 Heterogeneity.
AB  - The HIV-1 subtype distribution in 83 HIV-1-seropositive individuals living in
      Greece was investigated by using the heteroduplex mobility assay (HMA), DNA
      sequencing, and phylogenetic analysis. The results revealed that partial HIV-1
      gp120 sequences from 71 (86%) patients were subtype B, 5 (6%) were subtype A, 4
      were subtype D (5%), 2 (2%) were subtype C, and 1 (1%) was subtype I. The subtype
      I isolate was documented in an intravenous drug user. A high prevalence (90-100%)
      of B isolates among intravenous drug users, hemophiliacs, and homosexual men was
      observed, in contrast to heterosexuals, among whom non-B subtypes seemed to be
      common (42.9%, p < 0.001). Among the Greek population subtype B is the most
      frequent (94%), in contrast to the high prevalence (57%) of non-B isolates found
      in emigrants living in Greece (p < 0.001). A heterosexual transmission case of
      subtype D in a Greek individual not traveling abroad was also documented. The
      broad HIV-1 diversity in Greece may be explained by population movements, such as
      migration and traveling.

PMID- 9618082
TI  - Contribution of the CCR5 and MBL genes to susceptibility to HIV type 1 infection
      in the Finnish population.
AB  - Homozygosity for a variant of a chemokine receptor gene (CCR5) has been shown to
      protect from HIV-1 infection. Variants of the mannose-binding lectin (MBL) gene
      have been suggested to predispose to HIV-1 infection. These genetic variants and
      their possible role in susceptibility to HIV-1 infection were studied in sample
      material from more than 300 Finnish HIV-infected and control individuals. The
      genotyping was carried out efficiently using a novel, primer extension assay in a
      miniaturized oligonucleotide array format. Homozygotes for the protective
      deletion allele of the CCR5 gene were found only in the control group, and the
      frequency of the allele was high in the Finnish population. Homozygosity for the
      MBL variant alleles was enriched significantly in the HIV-1-infected group, thus
      providing further evidence for the harmfulness of MBL variant homozygosity in HIV
      1 transmission.

PMID- 9618083
TI  - Reciprocal interactions between human cytomegalovirus and human T cell leukemia
      lymphoma virus type I in monocyte-derived macrophages cultured in vitro.
AB  - Infection of macrophages with human cytomegalovirus (HCMV) has been shown to be
      nonlytic and exclusively cell associated. Human T cell leukemia-lymphoma virus
      type I (HTLV-I) is capable of establishing productive infection in macrophages.
      We studied the interactions between HCMV and HTLV-I in monocyte-derived
      macrophages cultured in vitro. We found that coinfection of macrophages with HCMV
      and HTLV-I significantly enhanced HCMV replication, resulting in release of
      infectious HCMV from dually infected cells. On the other hand, HCMV inhibited
      HTLV-I replication in macrophages coinfected with both viruses. Reciprocal
      interactions between HCMV and HTLV-I were mediated by their trans-acting
      proteins. Results of transfection studies demonstrated that the tax gene product
      of HTLV-I alone was capable of upregulating HCMV production. In a transient gene
      expression assay the immediate-early 2 (IE2) protein of HCMV alone could inhibit
      HTLV-I replication, whereas the IE1 protein, which had no effect by itself,
      produced a synergistic inhibitory effect together with the IE2 protein. Results
      from this study suggest that in vivo double infection of macrophages with HCMV
      and HTLV-I may contribute to the dissemination of HCMV infection in patients
      suffering from HTLV-I-associated T cell leukemia-lymphoma.

PMID- 9618084
TI  - Source and route of exposure influence infectivity of a molecular clone of human
      T cell leukemia virus type I.
AB  - Infection with human T cell leukemia virus type I (HTLV-I) is typically
      asymptomatic, but does result in diverse diseases ranging from adult T cell
      leukemia to spastic neuromyelopathy. To date, differences in HTLV-I provirus
      structure have not been correlated with pathogenic or asymptomatic outcome of
      infection. Molecular clones of HTLV-I are now available and represent a powerful
      tool to link virus structure to pathogenesis. Present studies to explore in vivo
      infectivity and pathogenicity of an HTLV-I molecular clone, K30p, have utilized
      the rabbit as a model system. This clone was administered to neonatal or adult
      rabbits by several different routes and infectivity and pathogenicity were
      examined. Detection of antiviral humoral immune responses, presence of provirus
      in tissue samples, and isolation of virus in cultures of blood lymphocytes were
      used to establish systemic HTLV-I infection. Intramuscular, but not nervous
      system, exposure to K30p HTLV-I naked DNA resulted in infection. Conversely,
      neural exposure to T cells that had been transfected with the K30p HTLV-I DNA
      consistently resulted in systemic infection. Despite detection of HTLV-I provirus
      in brain and spinal cord of some infected rabbits, no clinical or
      neuropathological changes occurred. Source and route of virus exposure played a
      role in infectivity, but did not influence the pathogenic outcome of HTLV-I
      infection.

PMID- 9618085
TI  - Size-heterogeneous sequences mark hot spots for asparagine, serine, and threonine
      insertions in HIV type 1 envelope.

PMID- 9618086
TI  - Trunk reconstruction with the free vastus lateralis flap.
AB  - A case is presented of a massive, full-thickness, trunk-wall defect successfully
      reconstructed with a free-tissue transfer of the entire vastus lateralis muscle.
      Indications, technical details, and donor-site considerations are discussed.

PMID- 9618087
TI  - Free-flap urethroplasty for a complex, long-segment stricture of the
      bulbomembranous urethra.
AB  - Long strictures of the bulbomembranous urethra are a challenge of modern urology,
      with no absolutely reliable technique for a favorable outcome. The authors
      describe a technique of urethroplasty using the radial forearm free flap, in a
      patient suffering from posttraumatic stricture, with excellent results.

PMID- 9618088
TI  - Reconstruction of upper-extremity peripheral-nerve injuries with ePTFE conduits.
AB  - This reported investigation was designed to determine the role of a new synthetic
      conduit-expanded polytetrafluoroethylene (ePTFE) tube--in clinical repair of
      median and ulnar nerves in the upper extremities. The main goals of this study
      were: to determine the effectiveness of the ePTFE conduit in clinical nerve
      reconstruction; to evaluate the potential of this technique in reconstruction of
      various nerve gaps (1.5 to 6 cm); and to analyze the results of repair with the
      ePTFE tube regarding different mechanisms of injury. Forty-three patients were
      evaluated. They had upper-extremity peripheral-nerve injuries (21 injuries to the
      median nerve, and 22 ulnar nerve injuries) located at the various levels of the
      upper extremities. All surgical procedures described in the study were secondary
      reconstructions, and the average delay from injury to repair was 4.2 months. With
      regard to the nerve-gap lengths, patients were categorized in two groups. Group 1
      (gaps from 1.5 to 4 cm) included 28 patients (17 median nerve injuries and 11
      ulnar nerve injuries), and Group 2 (gaps from 4.1 to 6 cm) comprised 15 patients
      (4 median nerve injuries and 11 ulnar nerve injuries). Results showed that 78.6
      percent of patients from Group 1 demonstrated functional motor and sensory
      recovery, while reconstruction of only 13.3 percent of peripheral nerves from
      Group 2 resulted in useful reinnervation. According to published results, ePTFE
      conduit is a reliable and successful surgical procedure for nerve repair in
      reconstruction of nerve gaps up to 4 cm between the ends of median and ulnar
      nerves in various levels of the upper extremity. Because of its properties, ePTFE
      conduit has the advantages of promoting better nerve regeneration, compared to
      other synthetic tubes, especially in reconstruction of proximal nerve injuries,
      larger nerve gaps, and in cases with unfavorable mechanisms of nerve injury.

PMID- 9618089
TI  - Milking dilatation: a pilot study.
AB  - Under certain circumstances during microsurgical anastomosis, vasospasm may
      persist, despite the use of multiple topical vasodilators. Mechanical dilatation
      may be needed but is difficult to perform in vessels smaller than 1 mm in
      diameter. Milking dilatation, a simple maneuver similar to a milking patency
      test, is introduced and tested for vessels of such a size. The femoral arteries
      of 10 Sprague-Dawley rats were used. Milking dilation was performed on both
      sides, and a forceful milking dilation method was also used 10 times on one side
      subsequently. The dilated segments demonstrated a 67.3 percent (29 to 100
      percent) increase in their original sizes. The vessels were all patent, with no
      gross signs of thrombosis or aneurysm formation, when exposed immediately, 1
      week, and 4 weeks post procedure. Half of the dilated segments, even those
      forcefully dilated, returned to their normal size at 4 weeks; the remainder were
      still dilated. The results of this study demonstrated that milking dilatation is
      effective and safe for dilating arteries about I mm in diameter or less. However,
      further study is required before any long-term conclusions can be drawn.

PMID- 9618090
TI  - The combined gracilis and semitendinosus free flap in the rat.
AB  - A free-flap model in rats is presented, that consists of gracilis and
      semitendinosus muscles pedicled on the femoral vessels, in continuation with deep
      femoral and saphenous vessels. This flap was transferred to the contralateral
      side in 40 rats and yielded a 95 percent survival rate. The weight of the flaps
      averaged 1.65 gm, and the mean pedicle length was 20 mm. The flap is reliable,
      versatile, and may be used as a muscular, musculocutaneous, or
      osteomusculocutaneous free flap. The gracilis and semitendinosus muscles may be
      innervated independently as functioning muscle units. In the musculocutaneous
      flap, each pedicle may be monitored separately by raising two independently
      vascularized skin islands. The statistical distribution of the origins of the
      deep femoral vessels was established in 164 groin dissections; two origins of the
      vessels not previously described are reported here. The volume of the
      transferable tissue-about three times more than described in previous studies-and
      the reliability of the flap make it an ideal microsurgical, experimental model.

PMID- 9618091
TI  - A new experimental flap model in the rabbit: scapular osteomyocutaneous flap.
AB  - Despite the use of various types of osteomyocutaneous flaps in clinical practice,
      there are many unanswered questions regarding their basic physiology. Simple and
      reliable flap models are needed to investigate these problems. However, very few
      of these flap models have been described in small animals to date. The purpose of
      this study was to develop a new osteomyocutaneous flap model in the rabbit.
      Twenty adult New Zealand white rabbits, weighing 2.5 to 3.0 kg, were used in the
      reported experiment. In seven rabbits, the anatomy of the axillary vessels was
      studied by anatomic dissection and selective angiography. Based on this anatomic
      study, a new osteomyocutaneous flap, namely, the scapular osteomyocutaneous flap,
      is described in the rabbit model. The flap is composed of a skin island (16 x 8
      cm) in the scapular region, the latissimus dorsi and intrinsic shoulder muscles,
      and the whole scapula as the bony component The flap is based on the axillary
      vessels, while the skin island and the latissimus dorsi muscle are independently
      supplied by branches of the thoracodorsal vessels. The flap could thus also be
      considered as a combined flap model. As an island flap, the flap was replaced in
      situ in eight rabbits, and transferred to the anterior chest in two rabbits. In
      the remaining three animals, the flap was transferred to the groin as a free
      flap. The viability of each component of the flap was demonstrated by direct
      observation, microangiography, bone scintigraphy, India ink injection study, and
      histologic examination. The authors concluded that the flap is a simple and
      reliable osteomyocutaneous flap model, since its dissection is easy; there is a
      long vascular pedicle with large vessel diameters; and large amounts of skin,
      muscle, and bone are included.

PMID- 9618092
TI  - Long-term evaluation of the behavior of a polytetrafluoroethylene microprosthesis
      in the rat iliac artery: myointimal regression.
AB  - The present study represents a long-term investigation of polytetrafluoroethylene
      (PTFE) vascular microprostheses implanted in the right common iliac artery of
      rats, with the aim of evaluating the degree of intimal hyperplasia and the
      changes produced in the vascular prosthesis. A follow-up study was performed
      between 3 months and 1 year post-implantation, using immunohistochemical
      techniques, light, and electron microscopy. Three months after implantation, the
      PTFE segment appeared sandwiched between two cell layers. A general
      endothelialization was observed on the luminal surface. The underlying myointima
      appeared as an irregular lining of decreasing thickness, from the distal
      anastomosis with the receptor artery to the proximal suture. A large number of
      white blood cells were found adherent to and infiltrating the endothelium. A
      neoformed adventitia covered the prosthesis on the external surface. At 4 months
      post-implantation, a destabilization of the luminal surface was observed induced
      by white blood cells. A progressive reduction in the thickness of the myointimal
      layer was also apparent, so that 1 year after implantation, the luminal surface
      of the PTFE prosthesis was fully lined by a thin cell covering. There is good
      long-term tolerance to implanted PTFE microprostheses. The white blood cells
      present in the implant region appeared to play an important role in the long-term
      regression of intimal hyperplasia.

PMID- 9618093
TI  - Traumatic spinal accessory nerve palsy.
AB  - Spinal accessory nerve sections due to a purely traumatic origin are very rare.
      The authors report a case in which a total section of the spinal accessory nerve
      was observed after a glass-penetrating injury. The primary lesion was
      undiagnosed, and only late physical examination revealed a scapula alata with a
      deficiency in shoulder protrusion and elevation. Surgical exploration with direct
      suturing of the nerve was performed 2 months after the initial trauma; full
      restoration of muscle function was obtained 12 months after the surgical
      procedure. Pain, the dominant preoperative feature, totally disappeared after
      restoration of shoulder function. Although infrequent, spinal accessory nerve
      lesions must always be excluded in cases of penetrating injuries in the posterior
      triangle of the neck. Emphasis is placed on diagnosis and treatment of this
      condition.

PMID- 9618094
TI  - Does prior irradiation increase the risk of total or partial free-flap loss?
AB  - Answers to the question, "Does previous irradiation of a recipient site interfere
      with reconstruction by free-tissue transfer?" have been elusive. In an attempt to
      address that question, all free-flap procedures performed for reconstruction of
      the breast or of head and neck defects at the University of Texas M. D. Anderson
      Cancer Center between May 1, 1988 and February 15, 1996 were reviewed. The
      effects of prior irradiation of the recipient site on the incidence of total flap
      loss, partial flap loss, and thrombosis were assessed. During the study period,
      1384 eligible free-flap reconstructions were performed. Total flap loss and
      partial flap loss were more common in the 428 flaps transferred to previously
      irradiated sites than in the patients without previous irradiation, but multiple
      logistic regression analysis showed that these differences were due to
      confounding factors. The authors conclude that previous irradiation of flap
      recipient sites does not statistically significantly affect the rate of partial
      or total free-flap loss.

PMID- 9618095
TI  - Temporary and retrievable inferior vena cava filters: current status.

PMID- 9618096
TI  - The role of radiation therapy in the management of vascular restenosis. Part II.
      Radiation techniques and results.

PMID- 9618097
TI  - Investigation of antibiotic prophylaxis usage for vascular and nonvascular
      interventional procedures.
AB  - PURPOSE: To investigate current antibiotic prophylactic usage for arteriography,
      angioplasty, vascular stent placement, transjugular intrahepatic portosystemic
      shunt placement (TIPS), tunneled-port placement, inferior vena cava (IVC) filter
      placement, biliary drainage, genitourinary drainage, abdominal drainage, and
      enteral tube placement with an aim to better clarify indications and regimens for
      prophylaxis. METHODS: A questionnaire regarding antibiotic prophylactic usage was
      sent to 2,039 members of the Society of Cardiovascular and Interventional
      Radiology (SCVIR). There were 401 respondents. Replies were evaluated for
      frequency and indications of prophylaxis, specific prophylaxis used, and clarity
      of indications for prophylaxis. RESULTS: A majority of responders never used
      prophylaxis for arteriography, angioplasty, vascular stent placement, IVC filter
      placement, abdominal drainage, and enteral tube placement. Infective complication
      rates from nonusage ranged between 1% and 15%. Approximately 45% always used
      prophylaxis for tunneled-port placement and TIPS with a 13%-16% infective
      complication rate among nonusers. In contrast, a majority of responders always
      used prophylaxis for biliary and genitourinary drainage, with a 40%-58% infective
      complication rate in nonusers. More than 70% of responders believed that the
      indications for prophylaxis were not clear for arteriography, angioplasty,
      vascular stent placement, tunneled-port placement, TIPS, IVC filter placement,
      and enteral tube placement, and in contrast, that the indications for prophylaxis
      for biliary and genitourinary drainage were clear. Fifty-one percent of
      responders believed that indications for prophylaxis for abdominal drainage were
      clear. CONCLUSIONS: Indications for antibiotic prophylaxis are not clear to
      interventionalists for a large number of vascular and nonvascular interventional
      procedures. Prophylaxis appears unnecessary for routine arteriography,
      angioplasty, IVC filter placement, vascular stent placement, or enterostomy tube
      placement. Antibiotic prophylaxis is warranted for TIPS and tunneled-port
      placement. Conversely, indications for antibiotic prophylaxis are clear to
      interventionalists for biliary and genitourinary drainage procedures. Routine
      prophylaxis remains warranted for both.

PMID- 9618098
TI  - Determinants of intravenous conscious sedation for arteriography.
AB  - PURPOSE: To assess factors that determine the amount of drugs given for
      intravenous conscious sedation during arteriography. MATERIALS AND METHODS: Data
      from 254 patients undergoing infradiaphragmatic arteriography at three
      institutions were evaluated. The effect of age, sex, procedure time, attending
      physician, and institution on drug use was assessed by analysis of variance and
      covariance with repeated measures. In a subset of 34 patients, pain and anxiety
      scores before and after medication were correlated with drug scores. RESULTS:
      Institution identity and procedure time significantly affected the amount of
      medication used (both, P = .000). Patient's age and sex, and identity of the
      physician had no significant effects. While drug use was relatively constant in
      each institution among different staff physicians, the institutional differences
      prevailed when the same physicians performed procedures at different
      institutions. Drug deliveries did not correlate with anxiety and pain scores
      before or after medication. CONCLUSION: Habits and philosophies of particular
      institutions, rather than physician guidance or patients' needs, tend to govern
      the use of intravenous sedatives and analgesics. There is a need for a more
      patient-oriented standardization of intravenous conscious sedation and analgesia.

PMID- 9618099
TI  - Renal artery stent placement for the management of ischemic nephropathy.
AB  - PURPOSE: To evaluate the angiographic and clinical results of percutaneously
      implanted renal artery endoprostheses (stents) for the treatment of patients with
      ischemic nephropathy. MATERIALS AND METHODS: During a 52-month period, 45
      patients with azotemia (serum creatinine > or = 1.5 mg/dL) and atheromatous renal
      artery stenosis untreatable by, or recurrent after, balloon angioplasty were
      treated by percutaneous placement of Palmaz stents. Stent implantation was
      unilateral in 32 cases and bilateral in 11 cases. Clinical results were
      determined by measurements of serum creatinine and follow-up angiography.
      Clinical benefit was defined as stabilization or improvement in serum creatinine
      level. Angiographic patency was defined as less than 50% diameter recurrent
      arterial stenosis. RESULTS: Stent placement was technically successful in 51 of
      54 (94%) renal arteries. Technical failures were stent misdeployment requiring
      percutaneous stent retrieval (n = 2) and inadvertent placement distal to the
      desired position (n = 1). Complications included acute stent thrombosis (n = 1)
      and early initiation of hemodialysis (within 30 days; n = 1). There were two
      periprocedural deaths. With use of life-table analysis, clinical benefit was seen
      in 78% of patients at 6 months (n = 36), 72% at 1 year (n = 24), 62% at 2 years
      (n = 12), and 54% at 3 years (n = 3). In patients with clinical benefit, average
      creatinine level was reduced from 2.21 mg/dL +/- 0.91 before treatment to 2.05
      mg/dL +/- 1.05 after treatment (P = .018). Lower initial serum creatinine level
      was associated with a better chance of clinical benefit (P = .05). No other
      variables affected outcome, including patient age, sex, diabetes, implanted stent
      diameter, unilateral versus bilateral stent placement, or ostial versus nonostial
      stent positioning. Conventional catheter angiography or spiral computed
      tomographic (CT) angiography performed in 19 patients (28 stents) at a mean
      interval of 12.5 months demonstrated primary patency in 75%. Maintained stent
      patency appeared to correlate with renal functional benefit. CONCLUSIONS:
      Percutaneous renal artery stent placement for angioplasty failures or restenoses
      provides clinical benefit in most patients with ischemic nephropathy.

PMID- 9618100
TI  - Aortoiliac stent placement in patients treated for intermittent claudication.
AB  - PURPOSE: To assess the results of iliac artery stent placement for the treatment
      of patients with intermittent claudication. MATERIALS AND METHODS: Lesions in 90
      iliac arteries were treated in 65 patients with 111 Wallstents and 21 Palmaz
      stents. Stents were placed for symptoms of intermittent claudication classified
      as grade I, categories 1-3 by the SVS/ISCVS/SCVIR reporting standards. Sixty-two
      stenosed arteries and 28 chronically occluded arteries were treated. Patients
      were followed for up to 57.1 months (mean, 17.4 months +/- 14.9). RESULTS:
      Technical success was achieved in 87 of 90 iliac limbs (97%), with major
      complications in seven of 65 patients (11%). The 30-day mortality was zero. Mean
      pressure gradients across stenoses improved from 14.7 mm Hg +/- 9.8 to 1.4 mm Hg
      +/- 1.4 (P < .001). Ankle-brachial indices improved from 0.62 +/- 0.21 to 0.90 +/
      0.18 (P < .001). With use of the Rutherford criteria, 84% demonstrated +2 or +3
      improvement. The cumulative patency rates were 77%, 71%, 62%, and 62% at 1, 2, 3,
      and 4 years (standard error [SE] < 10%). Continued clinical and noninvasive test
      benefit was present in 80%, 80%, 73%, and 73% at 1, 2, 3, and 4 years,
      respectively (SE < 10%). CONCLUSIONS: Significant hemodynamic improvement can be
      achieved by percutaneous stent placement, with excellent clinical results.
      Observed mortality in this series was zero, but major complications, requiring
      modification of the treatment plan, were seen in 11% of patients. Clinical
      results were better than suggested using current accepting reporting standards
      for "patency."

PMID- 9618101
TI  - Results of renal angioplasty in nonspecific aortoarteritis (Takayasu disease).
AB  - PURPOSE: To evaluate the long-term results of percutaneous transluminal renal
      angioplasty (PTRA) in the management of renovascular hypertension caused by
      nonspecific aortoarteritis (Takayasu disease). MATERIALS AND METHODS: The results
      of 96 stenoses in 66 patients were retrospectively studied. The indications for
      PTRA included hypertension uncontrolled by single-drug therapy, evidence of
      greater than 70% diameter stenosis in the renal artery with a peak systolic
      gradient of greater than 20 mm Hg, and clinically inactive disease. RESULTS:
      Technical success was obtained in 91 (95%) stenoses in 62 patients. Clinical
      success was seen in 59 (89%) and included "cure" in 14 and "improvement" in 45
      patients. The stenosis decreased from 88% +/- 6% (range, 70%-100%) to 11% +/- 12%
      (range, 0%-40%), systolic pressure gradient decreased from 95 mm Hg +/- 22
      (range, 30-140 mm Hg) to 9 mm Hg +/- 8 (range, 0-30 mm Hg), blood pressure
      improved from 181 +/- 16 (range, 150-220)/115 +/- 10 (range, 90-146) to 136 +/-
      25 (range, 130-210)/86 +/- 16 (range, 80-130) mm Hg, and the drug requirement
      decreased from 3.9 +/- .6 (range, 2-5) to 1.1 +/- .9 (range, 0-3) (P value for
      all < .001). Complications included transient intrarenal arterial spasm in three
      patients, groin hematoma in two patients, and ipsilateral renal vein injury in
      one patient. At 22 months +/- 17 (range, 4-84 months) follow-up, the restenosis
      rate, as determined by recurrence of hypertension and angiographic demonstration
      of restenosis, was 16%. CONCLUSION: Despite some technical problems, PTRA is safe
      and effective in treating renovascular hypertension caused by nonspecific
      aortoarteritis. The complication rate is low.

PMID- 9618103
TI  - Transjugular intrahepatic portosystemic shunt constraining stent for the
      treatment of refractory postprocedural encephalopathy: a simple design utilizing
      a Palmaz stent and Wallstent.

PMID- 9618102
TI  - Treatment of hemodialysis access rupture during PTA with Wallstent implantation.
AB  - PURPOSE: To report the authors' experience in treatment of ruptures complicating
      percutaneous transluminal angioplasty (PTA) of hemodialysis access with
      implantation of a Wallstent. MATERIALS AND METHODS: Between January 1, 1990, and
      October 1, 1995, the authors performed 2,414 PTAs of angioaccesses. A severe
      rupture occurred in 40 (1.7%) of these procedures and was treated by means of
      stent placement. Wallstents were implanted in 37 of these ruptures. The
      angioaccesses comprised 22 grafts and 15 fistulas. The indications for stent
      placement were four isolated pseudoaneurysms and 33 cases of bleeding: 15 major
      leaks, five moderate leaks that persisted despite prolonged inflation at low
      pressure, seven leaks associated with greater than 50% residual stenosis, four
      leaks associated with pseudoaneurysm, and two leaks associated with both greater
      than 50% residual stenosis and pseudoaneurysm. Seventeen ruptures were located on
      a vein, 19 on the venous anastomosis of a graft, and one on a graft itself.
      RESULTS: Stent placement stopped the bleeding immediately in 28 cases and after
      prolonged inflation within the stent in four cases. Residual bleeding required
      implantation of a covered Cragg stent within the Wallstent in one case. A
      pseudoaneurysm was still visible at the end of the intervention in 11 cases. Two
      complications occurred; one hematoma was drained surgically and one access
      occluded on day 2. Follow-up angiography showed a small pseudoaneurysm in only
      one patient with impaired platelet function. The primary and secondary patency of
      the angioaccesses were 48% and 86% at 1 year, respectively. CONCLUSION: Wallstent
      implantation is very effective for both immediate and long-term treatment of
      rupture of angioaccess during PTA.

PMID- 9618104
TI  - Use of a purse string suture to close a percutaneous access site after
      hemodialysis graft interventions.

PMID- 9618105
TI  - Doppler flow wire evaluation of renal artery blood flow before and after PTA:
      initial results.

PMID- 9618107
TI  - Gianturco Z stents and the Hydrolyser catheter: a potential problem.

PMID- 9618106
TI  - Mesenteric venous thrombosis: successful treatment by intraarterial lytic
      therapy.

PMID- 9618108
TI  - "Monorail technique" for removal of entrapped exchange wire in a Greenfield
      filter.

PMID- 9618109
TI  - Tissue response to covered Wallstents.
AB  - PURPOSE: To evaluate and compare the healing response related to two types of
      graft-covered Wallstents (WSs) and an uncovered WS in the canine iliac artery.
      MATERIALS AND METHODS: Eight bare mesh WSs, 10 polyethylene terephthalate
      interbraided WSs (PET-WSs), and six polytetrafluoroethylene covered WSs (ePTFE
      WSs) were placed in the iliac arteries of 12 dogs. Arteriograms were obtained
      before and after implantation and at explantation. Devices were explanted at 1
      month (n = 8), 3 months (n = 6), and 6 months (n = 10) and sent for histologic
      study. RESULTS: One ePTFE-covered stent-graft was found to be thrombosed at 3
      months; the remaining 23 of 24 implants remained patent to the time of
      explantation. The WS and ePTFE-WS both generated a uniform myointimal cell
      response without inflammation. The PET-WS induced a fibrous luminal response with
      substantial foreign body-type inflammatory reaction around the PET fibers.
      Although neointima associated with the PET-WS appeared thicker than that
      associated with either the ePTFE-WS or the bare WS, none of the patent implants
      developed greater than 50% angiographic narrowing. CONCLUSION: The PET-WS induced
      chronic inflammation, a response not seen with either the WS or ePTFE-WS. This
      may explain the occurrence of pain and/or fever in human studies of arterial PET
      endoluminal stent-grafts. Patency for all three implants was excellent in this
      model.

PMID- 9618110
TI  - Resistance of freshly adherent endothelial cells to detachment by shear stress is
      matrix and time dependent.
AB  - PURPOSE: The placement of endothelial cells on the surfaces of arteries
      immediately after vascular interventions has the potential to limit restenosis by
      inhibiting intimal thickening and by stimulating arterial enlargement. Because
      such re-endothelialization is dependent on rapid formation of strong endothelial
      cell-matrix interactions, experiments were performed to identify the
      extracellular matrix that provided endothelial cells with the greatest resistance
      to detachment by a shear stress in the least amount of time. MATERIALS AND
      METHODS: Rabbit microvascular endothelial cells were plated onto glass slides
      coated with collagen, laminin, vitronectin, or fibronectin. After allowing 5-45
      minutes for cell adhesion, each slide was placed in a parallel plate chamber, and
      the number of cells present before and after exposure of the cells to shear
      stresses (1-25 dynes/cm2) were counted. RESULTS: Endothelial cell retention to
      the matrix-coated slides was time and matrix dependent. The percentages of
      endothelial cells retained after adhesion times of 5, 15, 30, and 45 minutes
      followed by exposure to 15 dynes/cm2 were 9%, 20%, 32%*, and 38%* for collagen;
      7%, 20%, 36%*, and 49%* for laminin; 35%, 47%, 62%, and 76%* for vitronectin; and
      64%, 58%, 71%, and 78% for fibronectin, respectively (*P < .05 versus 5 minutes
      adhesion). Similar results were obtained for lower and higher shear stresses,
      indicating that cell retention was independent of shear stress above 1 dyne/cm2.
      CONCLUSIONS: The resistance of freshly adherent endothelial cells to detachment
      by shear stress is matrix- (fibronectin approximately equal to vitronectin >
      laminin approximately equal to COL) and time-dependent. Fibronectin provided the
      greatest cell retention in the least amount of time.

PMID- 9618111
TI  - Site-specific delivery of iloprost during experimental angioplasty suppresses
      smooth muscle cell proliferation.
AB  - PURPOSE: The authors have previously reported that intramural delivery of
      iloprost during angioplasty suppresses local platelet aggregation at 1 hour in
      undiseased porcine arteries. In this study, the authors sought to quantify the
      effect of such treatment on medial vascular smooth muscle cell proliferation, an
      event implicated in the development of intimal hyperplasia. MATERIALS AND
      METHODS: Three Yorkshire pigs underwent percutaneous transluminal angioplasty
      with hydrogel-coated balloons for a total of 10 iloprost-treated (experimental)
      and 10 saline-treated (control) arterial sites. The balloons were prepared with
      previously reported techniques and loaded with 2.25 microg of iloprost for the
      experimental sites. On the eighth day after angioplasty, these sites were
      harvested and prepared for immunohistochemical staining. Thin (4 microm) sections
      of the specimens were stained with use of monoclonal antibody to proliferating
      cell nuclear antigen (PCNA). Appropriate positive and negative controls were
      used. Approximately 350-500 vascular smooth muscle cells were randomly counted
      under high power (100x) by an experienced physician who was blinded to the origin
      of the specimen. A PCNA index (%) was calculated as follows: [(#PCNA [+]
      cells)/(#PCNA [+] cells + #PCNA [-] cells)]x 100. A paired t test was used for
      statistical comparison. RESULTS: The PCNA indices for eight (n = 8) paired large
      vessels (iliac, carotid, subclavian) were 7.98 (+/- 1.8)%, for the iloprost
      treated experimental sites, and 14.58 (+/- 3.8)% for the saline-treated control
      sites. This difference was statistically significant (P = .003). One large vessel
      pair was not available for analysis. When the pair of renal arteries of animal 3
      were included (n = 9), the PCNA indices were 8.32 (+/- 2.3)% for the experimental
      sites, and 13.79 (+/- 4.2)% for the control sites. The differences were again
      significant (P = .01). CONCLUSION: Intraarterial site-specific delivery of
      iloprost during angioplasty with drug-loaded, hydrogel-coated balloons
      significantly suppresses medial smooth muscle cells in swine at the expected peak
      period of proliferation of 7 days after angioplasty.

PMID- 9618112
TI  - Transcatheter oily chemoembolization of the inferior phrenic artery in
      hepatocellular carcinoma: the safety and potential therapeutic role.
AB  - PURPOSE: To evaluate the efficacy and safety of transcatheter oily
      chemoembolization therapy (TOCE) via the inferior phrenic artery (IPA) in
      hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Fifty patients with HCC
      underwent a total of 82 procedures of TOCE of the IPA, as well as of the hepatic
      artery. In 16 patients, additional extrahepatic collaterals were depicted and
      were also embolized in 10 patients. TOCE was performed with an emulsion of
      iodized oil and doxorubicin hydrochloride, and gelatin sponge particle
      embolization was added in 32 patients. RESULTS: Initial response showed complete
      or partial remission of the tumor in 31 patients. The cumulative survival rates
      after combined TOCE of the hepatic artery, IPA, and other extrahepatic arteries
      were 89% (6 months), 78% (1 year), 46% (2 year), and 30% (3 year), when
      calculated from the time of IPA chemoembolization. Liver abscess and empyema
      developed in one case of combined IPA and multiple intercostal artery
      chemoembolization. There were no serious complications after IPA
      chemoembolization alone. CONCLUSION: TOCE of the IPA has a potential therapeutic
      role as a safe adjunct to TOCE of the hepatic artery in the management of HCC
      supplied by the IPA.

PMID- 9618113
TI  - Subsegmental transcatheter arterial embolization for hepatocellular carcinoma in
      the caudate lobe.
AB  - PURPOSE: To clarify the effectiveness of transcatheter arterial embolization
      (TAE) for hepatocellular carcinoma (HCC) in the caudate lobe of the liver.
      MATERIALS AND METHODS: Thirteen patients with HCC in the caudate lobe underwent
      TAE. TAE was performed by injection of the mixture of anticancer drugs (mitomycin
      C and doxorubicin or epirubicin) and iodized oil, followed by gelatin sponge
      particles. Arterial anatomy of the caudate branch, local recurrence rate, and
      survival rate were evaluated. RESULTS: From 31 TAEs for the caudate lobe, 22
      subsegmental TAEs were successfully performed (71%). Local recurrence in the
      caudate lobe was seen in 10 patients (77%). Subsegmental TAE for the caudate lobe
      was repeated one to five times. Cumulative local recurrence rates were 33% and
      75% within 3 and 6 months, respectively. Survival rates after first TAE for HCC
      in the caudate lobe were 89% and 74% for 1 and 3 years, respectively. CONCLUSION:
      Local recurrence rate after subsegmental TAE for HCC in the caudate lobe was
      high. However, repeated subsegmental TAE possibly improves the prognosis of HCC
      in the caudate lobe.

PMID- 9618114
TI  - Congenital intrahepatic portosystemic shunts in the neonate: coil embolization
      via the umbilical vein.

PMID- 9618115
TI  - Wide-necked saccular renal artery aneurysm: endovascular embolization with the
      Guglielmi detachable coil and temporary balloon occlusion of the aneurysm neck.

PMID- 9618116
TI  - Manual thromboaspiration and dilation of thrombosed dialysis access grafts: mid
      term results of a simple concept.

PMID- 9618117
TI  - Giant right atrial thrombus: a life-threatening complication of long-term central
      venous access catheters.

PMID- 9618118
TI  - Transjugular liver biopsy through a TIPS Wallstent.

PMID- 9618119
TI  - Sudden death in a patient caused by migration of an Antheor vena cava filter to
      the heart.

PMID- 9618120
TI  - Demonstration of pathologic shunting during pulmonary angiography in a case of
      bronchioloalveolar carcinoma.

PMID- 9618121
TI  - Circulating insulin concentrations, smoking, and alcohol intake are important
      independent predictors of leptin in young healthy men.
AB  - OBJECTIVE: Leptin, an adipocyte-secreted hormone, has been shown to signal the
      status of energy stores to the brain, regulate energy homeostasis, and mediate
      the neuroendocrine response to food deprivation. Obesity is associated with
      increased leptin levels, and several hormones, including insulin and
      glucocorticoids, have been associated with leptin levels and expression in
      rodents. Although obesity has been strongly associated with increased leptin in
      humans, a significant percentage of leptin's variability remains unexplained. The
      role of endogenous hormones, demographic factors, or certain life-style factors
      in explaining the residual variability of leptin levels has not yet been
      clarified. We performed this cross-sectional study to document the relative
      importance of obesity, lifestyle factor, and endogenous hormones in determining
      serum leptin levels. RESEARCH METHODS AND PROCEDURES: We measured serum
      concentrations of insulin, cortisol, testosterone, growth hormone, and
      dehydroepiandrosterone sulfate; ascertained anthropometric, demographic, and
      lifestyle characteristics; and studied these variables in relationship to serum
      leptin concentrations in a sample of young healthy men. RESULTS: Obesity and
      alcohol intake were independently and positively associated with circulating
      leptin concentrations. Additionally, cigarette smoking was negatively and
      independently associated with leptin concentrations. Finally, serum insulin
      concentration was an independent hormonal determinant of circulating leptin
      concentrations, whereas serum testosterone was negatively associated with leptin
      only by bivariate analysis. DISCUSSION: We conclude that, in addition to obesity,
      cigarette smoking, alcohol intake, and serum insulin levels are associated with
      leptin levels in a population of healthy young men.

PMID- 9618122
TI  - Blood pressure in adolescence and early adulthood related to obesity and birth
      size.
AB  - OBJECTIVE: Obesity is an established risk factor for higher systolic (SBP) and
      diastolic (DBP) blood pressure in adolescence and early adulthood, but birth size
      may also have a role. We analyzed the effects of adolescent and adult obesity and
      birth size on BP in the young adult. RESEARCH METHODS AND PROCEDURES: In a
      prospective longitudinal study, anthropometric measurements were obtained at
      birth on 67 boys and 67 girls born in Boston. Their body mass indices (BMI) and
      BP were recorded 17 years and 30 years later. RESULTS: For women, adolescent and
      early adult obesity appeared to be the stronger determinants of higher BP,
      although smaller head and chest circumferences at birth may also be related. We
      found some evidence of birth (ponderal index [PI] and head circumference)
      anthropometric influences on age 17 BP levels in boys. By age 30, body mass
      variables were the dominant predictors of male BP levels. Female BMI at age 17
      was positively correlated with birth adiposity (PI), but BMI at 30 was related
      only to age 17 BMI. Similarly, male BMI at 17 years was higher for those who
      weighed more at birth, but BMI at 30 years was again related only to age 17 BMI.
      DISCUSSION: We conclude that adult weight and weight gain are the major
      determinants of adult BP.

PMID- 9618123
TI  - Prader-Willi syndrome: relationship of adiposity to plasma leptin levels.
AB  - OBJECTIVE: Prader-Willi syndrome (PWS) is an autosomal dominant disorder
      involving the proximal long arm of chromosome 15, in which obesity is common.
      However, there is limited information on the underlying physiological mechanisms
      promoting obesity in this population. We tested whether there was a significant
      positive association between leptin and total body fat (TBF) in subjects with
      PWS, and whether this association was stronger among subjects with than without
      PWS. RESEARCH METHODS AND PROCEDURES: We studied 21 PWS patients and 64 non-PWS
      controls on whom we measured serum leptin, total body fat, glucose, insulin, and
      resting energy expenditure. We tested whether the slope of the regression line
      between leptin and TBF (in kg), measured by dual energy X-ray absorptiometry, was
      the same for PWS patients and non-PWS controls. RESULTS: Regression analyses
      indicated that the leptin-TBF association was significantly stronger among PWS
      patients. In contrast, the slope of the leptin-body mass index association did
      not significantly differ between PWS patients and non-PWS controls. None of the
      other outcome variables showed associations with leptin. DISCUSSION: Results
      suggest that the role of leptin in promoting obesity may be greater among
      subjects with PWS than among non-PWS controls.

PMID- 9618124
TI  - The efficacy of dietary fat vs. total energy restriction for weight loss.
AB  - OBJECTIVE: Dietary fat restriction is currently being promoted as a weight loss
      strategy. However, previous investigations suggest that fat restriction alone may
      not be more beneficial than total energy restriction for the treatment of
      obesity. The purpose of this project was to assess whether an energy-restricted
      or fat-restricted diet was more effective at promoting weight loss, improving
      eating behaviors, and reducing barriers to dietary adherence. RESEARCH METHODS
      AND PROCEDURES: Eighty individuals (15 men and 65 women) were randomized into the
      two treatment conditions. Subjects were 120% to 140% of ideal body weight and 25
      years to 45 years old. Treatment consisted of 24 weeks of dietary fat (22 g/day
      to 26 g/day) or energy restriction (4,186 kJ/day to 5,023 kJ/day), including
      behavior modification and exercise. Body weight change, dietary intake, eating
      behaviors, and barriers to adherence were measured at baseline and after
      treatment. RESULTS: Results show that subjects in the energy-restricted condition
      lost over twice as much weight as those in the fat-restricted group (11.5 kg vs.
      5.2 kg). Additionally, subjects in the low-energy condition had greater
      improvements in eating behavior scores, enhanced feelings of wellness, a greater
      distaste for dietary fat, and no more pronounced feelings of deprivation than did
      those in the fat-restricted condition. DISCUSSION: An energy-restricted diet
      produces greater short-term weight loss than dietary fat restriction without many
      of the negative consequences commonly attributed to reducing energy intake.

PMID- 9618125
TI  - Improved psychological well-being, quality of life, and health practices in
      moderately overweight women participating in a 12-week structured weight loss
      program.
AB  - OBJECTIVE: To study the effects of a 12-week weight loss strategy involving
      increased physical activity, self-selected hypocaloric diet, and group support on
      psychological well-being, quality of life, and health practices in moderately
      obese women. METHODS: Eighty women aged 20-49 years weighing between 20-50% above
      1983 Metropolitan Life Insurance Tables were randomly assigned to a weight loss
      intervention (6279 kJ/week of physical activity, 33,258-41,462 kJ/week diet and
      weekly meetings) or served as controls. Subjects were tested pre and post 12
      weeks. RESULTS: The intervention group lost significant (p<0.001) body weight
      (kg) and body fat (%) compared to controls (-6.07+/-4.01 kg vs. 1.31+/-1.28 kg;
      36.8%-32.5% vs. 36.2%-36.0%). Intervention subjects vs. controls achieved
      significant improvements (p<0.001) in body cathexis (X Change 18.6+/-16.7 vs.
      0.7+/-8.6) and estimation of ability to achieve physical fitness (X Change 8.1+/
      7.1 vs. 0.9+/-5.9). Various quality of life indices also improved (p<0.01) in the
      intervention group compared to controls (physical function: X Change 13.5.2+/
      16.7 vs. 1.4+/-9.5; vitality: X change 21.7+/-17.9 vs. 2.9+/-20.8; mental health:
      X change 10.4+/-16.0 vs. 2.3+/-10.1). Similarly, physical activity levels also
      improved significantly (p<0.0001) in the intervention group (4.4+/-2.3 vs. 0.6+/
      1.3; on NASA 0-7 scale). CONCLUSIONS: Practical weight loss practices such as
      increased activity, self-selected hypocaloric diet, and group support are
      effective for weight loss and yield significant health and psychological benefits
      in moderately obese females.

PMID- 9618126
TI  - Further support for consistent self-monitoring as a vital component of successful
      weight control.
AB  - OBJECTIVE: This study attempted to replicate that of Baker and Kirschenbaum by
      providing a descriptive analysis of the relationship between self-monitoring and
      weight control. PROCEDURES: Fifty-nine women and men in long-term cognitive
      behavioral treatment for obesity participated over an 8-week period. Percentages
      of participants who self-monitored consistently and the relationship between the
      variability in self-monitoring and weight change were examined. RESULTS: As in
      the previous study, a substantial minority of the participants in this research
      (26.3%) self-monitored all foods eaten on less than half of the days evaluated.
      The assertion of Baker and Kirschenbaum that self-monitoring is most
      appropriately viewed as both a state and a trait was supported by finding that
      the most consistent self-monitors lost more weight than the least consistent self
      monitors; however, regardless of overall self-monitoring consistency,
      participants lost much more weight during their two most consistent weeks
      compared with their two least consistent weeks. Again, as in the previous study,
      only the more consistent quartile of self-monitors lost a substantial amount
      during the course of this study. DISCUSSION: The results of both studies taken
      together suggests that a reasonable target for consistency for self-monitoring
      within the context of a professional cognitive-behavioral treatment program may
      be self-monitoring all foods eaten on at least 75% of the days. If participants
      generally self-monitor on less than half of the days during participation in such
      programs, they may be very unlikely to succeed at weight loss both during the
      program and afterward.

PMID- 9618127
TI  - Relationship between hunger-satiety feelings and various metabolic parameters in
      women with obesity during controlled weight loss.
AB  - OBJECTIVE: Satiety plays an important role in weight control. The meaning of
      fasting hormone levels and satiety feelings, and how post-absorptive changes
      after meals high in carbohydrate regulate appetite remains to be demonstrated.
      RESEARCH METHODS AND PROCEDURES: Prospective metabolic study with 25 non-diabetic
      obese women at the Energy Metabolism Research Unit of the Department of Nutrition
      Sciences, University of Alabama at Birmingham. We analyzed fasting and
      postprandial ratings of hunger-satiety and values of various metabolic parameters
      (serum glucose and insulin, plasma cholecystokinin, respiratory quotient) during
      controlled weight loss. The postprandial measures were assessed following a test
      meal providing 320 kcal and yielding a food quotient of 0.89. RESULTS: In the
      fasting state, there was no correlation between hunger-satiety ratings and any of
      the measured metabolic parameters. Under postprandial conditions, satiety was
      positively related to glucose (p=0.002) and insulin (p=0.002) responses to the
      test meal. In multivariate analysis including glucose, insulin, cholecystokinin,
      hunger-satiety ratings and respiratory quotient, insulin was the only independent
      predictor of satiety in the postprandial state. DISCUSSION: These data suggest an
      association between the endogenous insulin response and feelings of postprandial
      satiety. Insulin's satiation properties, which could well be mediated by other
      hormones, may represent a primary factor of food intake regulation after meals
      relatively high in carbohydrate.

PMID- 9618128
TI  - Beliefs about weight gain and attitudes toward relapse in a sample of women and
      men with obesity.
AB  - OBJECTIVE: The purpose of this study was to examine beliefs regarding reasons for
      weight gain, likely responses to weight loss relapse, notions of reasonable
      weight loss, and correlations between beliefs and attitudes in a large
      nonclinical sample of men and women with obesity. RESEARCH METHODS AND
      PROCEDURES: Participants were 3,394 white women (n=1,674) and men (n=1,720) with
      obesity who had responded to a survey about body image and eating behaviors
      conducted by Consumer Reports magazine. RESULTS: Women and men indicated that the
      most important reasons for their weight gain were lack of exercise and enjoying
      eating; the least important reason was a need to avoid social or sexual
      situations. Both groups reported that their most likely response to relapse is to
      start watching food intake, whereas their least likely response is to ask a
      friend, spouse, or family member for help. Women rated depression, stress, low
      self-esteem, and need to avoid situations as more important reasons for their
      weight gain than did men, and women were more likely to feel terrible and regain
      as a response to relapse. There was no relationship between an individual's
      beliefs about weight gain, responses to relapse, or notions of reasonable weight
      loss. DISCUSSION: Implications of these findings for the treatment of obesity are
      discussed.

PMID- 9618129
TI  - Diabetes in urban African Americans. XII. Anthropometry for assessing municipal
      hospital outpatients recently diagnosed with type 2 diabetes.
AB  - OBJECTIVE: Abdominal obesity is associated with insulin resistance and
      cardiovascular risk factors, but there has been little information published to
      advance the use of abdominal anthropometry in the care of diabetic patients.
      RESEARCH METHODS AND PROCEDURES: A cross-sectional survey of municipal hospital
      outpatients recently diagnosed with type 2 diabetes (73 men and 142 women of whom
      89% were African Americans). Age-adjusted linear regression was used to compare
      the supine sagittal abdominal diameter (SAD), supine waist circumference, four
      anthropometric ratios, and the body mass index (kg/m2) for their ability to
      predict serum fasting C-peptide and lipid levels. RESULTS: The best predictor of
      log-transformed C-peptide was SAD/height (p<0.0001 for men; p=0.0003 for women).
      SAD/thigh circumference was the best predictor of log-transformed triglycerides
      for men (p=0.002) and of total cholesterol/HDL cholesterol for women (p=0.043).
      The body mass index was less able to predict C-peptide, HDL cholesterol and total
      cholesterol/HDL cholesterol than was SAD/height or SAD/thigh circumference or
      waist circumference/height. DISCUSSION: Anthropometric indices of abdominal
      obesity appear to be correlated with insulin production and lipid risk factors
      among municipal-hospital, type 2 diabetic patients much as they are in other
      studied populations. Since anthropometric data are inexpensively obtained and
      immediately available to the practitioner, their utility for preliminary clinical
      assessment deserves to be tested in prospective outcome studies.

PMID- 9618130
TI  - Effects of the menopause transition on body fatness and body fat distribution.
AB  - OBJECTIVE: The menopause transition increases cardiovascular and metabolic
      disease risk, partly because of the adverse effects of estrogen deficiency on the
      plasma lipid-lipoprotein profile and cardiovascular function. This increased
      cardiovascular and metabolic disease risk may also be partially mediated by
      increased body fat, increased intra-abdominal adipose tissue accumulation, or
      both. The objective of this mini-review is to summarize studies that have
      investigated the relationships among the menopause transition, body fatness, and
      body fat distribution. RESEARCH METHODS AND PROCEDURES: A review of cross
      sectional and longitudinal studies on menopause that examined body fatness and
      body fat distribution. RESULTS: Cross-sectional reports show that the menopause
      transition is related to modest increases in body mass index or total fatness,
      although not all studies found significant effects. Increased central adiposity
      appears to be related to menopause, independent of advancing age, but these
      results are methodology dependent. An independent effect of menopause on central
      body fatness was noted by the use of techniques such as DEXA or computed
      tomography, whereas studies using circumference measures showed discrepant
      results. Longitudinal studies showed that the menopause transition accelerated
      the increase in central adiposity, although no studies quantified changes in
      intra-abdominal fat by imaging techniques. DISCUSSION: Thus, additional
      longitudinal studies using more accurate measures of adiposity are needed to
      critically examine the effects of the menopause transition on total and central
      body fatness. Collectively, previous studies suggest that menopause is related to
      modest increase in total fatness and accelerated accumulation of central body fat
      that exceeds changes normally attributed to the aging process. These changes may
      increase the risk for cardiovascular and metabolic disease in aging women.

PMID- 9618131
TI  - Investigative techniques in the assessment of oral-pharyngeal dysphagia.
AB  - Oral-pharyngeal dysphagia is a common problem with a high morbidity and
      mortality. In general, it is not managed as well as esophageal dysphagia by
      gastroenterologists. A number of techniques are now available for the assessment
      of oral-pharyngeal dysphagia. However, a careful clinical assessment followed by
      a video barium swallow is all that is required for the diagnosis and management
      in the majority of patients. Pharyngeal manometry is likely to play an
      increasingly important role in the assessment of difficult or atypical cases in
      whom it can provide functional information not achievable with videoradiography
      alone. Videolaryngoscopy is a quick and simple way of detecting structural
      lesions and of assessing deglutitive airway protection. Videolaryngoscopy is non
      invasive and easily performed in an office setting. Ultrasonography is a
      convenient way of assessing lingual function, but provides no more information
      than the video barium swallow. Pharyngeal scintigraphy is likely to assume a
      greater clinical relevance as a means of quantifying swallow efficiency and
      response to therapy.

PMID- 9618132
TI  - Endoscopic therapy of chronic and recurrent pancreatitis.
AB  - Endoscopic pancreatic therapy is emerging as an exciting nonoperative alternative
      in the management of chronic pancreatitis, in particular in cases where
      pancreatic duct obstruction due to stones, protein plugs, or strictures is
      present. Although the preliminary results available are promising, prospective
      randomized trials comparing endoscopic and surgical techniques are much needed.
      Furthermore, the published data come from large endoscopic centers with very high
      levels of technical skill and experience, and, therefore, its wide-spread
      clinical use is limited. Time and well-designed prospective randomized clinical
      trials comparing surgical versus endoscopic techniques will help define the role
      of these procedures in the treatment of chronic pancreatitis.

PMID- 9618133
TI  - Zenker's diverticulum.
AB  - Zenker's diverticulum is a pouch protruding posteriorly above the upper
      esophageal sphincter, in the Killian's triangle, an area of relative weakness.
      Zenker's diverticulum was thought, for many years, to occur as a result of
      cricopharyngeal incoordination but more recent evidence points to poor upper
      sphincter compliance with diminished sphincter opening and increased
      hypopharyngeal pressures. Small Zenker's diverticula may be asymptomatic. As they
      become larger, symptoms include dysphagia, food regurgitation, and a sensation of
      globus. The best diagnostic method is a barium swallow with attention to the
      cricopharyngeal area. Although gastroesophageal reflux may be responsible for
      many throat symptoms, the relationship of reflux to the pathogenesis of Zenker's
      diverticulum is speculative. The treatment of Zenker's diverticulum is surgical.
      There have been many variations in technique over the years. Diverticulectomy
      with cricopharyngeal myotomy remains the most frequently performed operation.
      Endoscopic treatment with or without laser stapling has been reported but is not
      popular in the United States.

PMID- 9618134
TI  - Oxidative stress and antioxidants in intestinal disease.
AB  - Oxidative injury caused by free radicals is an important cause of tissue injury
      now recognized to occur in inflammation, ischemia and by the action of
      xenobiotics. It is also recognized to induce gene mutation and promote
      carcinogenesis. In this review the general concept of nett free radical injury
      counterbalanced by antioxidants is discussed as oxidative stress. The role of
      oxidative stress in intestinal ischemia, radiation enteritis, inflammatory bowel
      disease and the promotion of gastric and colorectal cancer is discussed. The data
      for the role of oxidative stress in the pathogenesis of ischemic, inflammatory
      and radiation induced disease are strong, but interventional studies with
      antioxidants have shown only weak beneficial effects in the above diseases.
      Therefore the role of antioxidants in the therapy of gastrointestinal diseases
      remains controversial and should be the subject of controlled trials.

PMID- 9618135
TI  - Gastric stump cancer: what is the risk?
AB  - Patients who have undergone partial gastric resections are at an increased risk
      for the development of cancer in the gastric remnant. The overall risk increases
      over time and is higher in patients with an initial diagnosis of gastric rather
      than duodenal ulcer, in men and following partial gastrectomy with Billroth II
      reconstruction. The site of tumor growth is predominantly in the anastomotic
      area, but may occur anywhere in the stump. Enterogastric reflux, achlorhydria,
      bacteria overgrowth, and Helicobacter pylori appear to be the major factors
      involved in the etiopathogenesis of the gastric stump cancer. Surveillance of
      these patients with endoscopy and multiple biopsies may provide the means to
      diagnose tumors at an early stage, but the cost-benefit ratio of surveillance
      requires further study. Despite the magnitude of alterations in gastric stump
      mucosa, unfortunately, at this time we do not have good predictors of patients
      who will develop a cancer.

PMID- 9618136
TI  - Gastrointestinal and hepatic manifestations of hereditary hemorrhagic
      telangiectasia.
AB  - Hereditary hemorrhagic telangiectasia (HHT) or Osler-Rendu-Weber (ORW) disease is
      an autosomal-dominant disorder that frequently presents with gastrointestinal
      bleeding which may be a diagnostic and therapeutic challenge. Hepatic involvement
      in this disease is increasingly recognized and poses another therapeutic
      challenge. With advances in genetic screening and diagnostic procedures, and the
      increasing awareness of the condition by physicians and patients, this disease is
      being diagnosed more often. This article reviews the available literature on
      gastrointestinal and hepatic manifestations of HHT, and the various diagnostic
      and therapeutic modalities available for its management.

PMID- 9618137
TI  - Overview of imaging in colorectal cancer.
AB  - Accurate staging of colorectal carcinoma (CRC) at initial diagnosis is critical
      for proper management of this disease. Computed tomography (CT) is often used for
      preoperative staging and is complementary to the clinical assessment of the
      patient and to the use of other imaging techniques, such as endoluminal
      ultrasound (US). CT can identify those patients who may benefit from local
      radiation therapy, hepatic resection or cryoablation, or intra-arterial
      chemotherapy. Endoluminal US may detect patients with early disease and alter
      their course of therapy, especially in those with rectal carcinoma in which
      limited surgery might be performed. CT is generally the modality of choice for
      imaging the postoperative patient. CT clearly depicts the operative area,
      particularly after abdominoperitoneal resection, and can be used to guide
      percutaneous biopsy of masses. The role of magnetic resonance imaging in CRC
      remains to be defined. In this review, we discuss the current roles of these
      various imaging modalities in the management of this disease.

PMID- 9618138
TI  - Diagnosis and management of appendiceal mucoceles.
AB  - Preoperative diagnosis of appendiceal mucoceles is rare. If untreated, one type
      of mucoceles may rupture producing a potentially fatal entity known as
      pseudomyxoma peritonei. The importance of diagnosing appendiceal mucoceles is
      highlighted through a case presentation of a woman who had an incidental finding
      of mucinous cystadenoma of the appendix during colonoscopic evaluation for occult
      gastrointestinal bleeding. A detailed review of the medical literature regarding
      appendiceal mucoceles is presented, with emphasis on the pathologic, clinical,
      radiologic, and evolving endoscopic features. Surgical options and prognosis are
      discussed.

PMID- 9618139
TI  - Transcriptional and posttranscriptional regulation of osteopontin gene expression
      in preosteoblasts by retinoic acid.
AB  - This study examines the relative importance of transcriptional and
      posttranscriptional actions of retinoic acid (RA) in the regulation of
      osteopontin gene expression in a rat clonal preosteoblastic cell line, UMR 201.
      Nuclear run-on analysis demonstrated constitutive expression of the osteopontin
      gene which was increased by threefold after 4 hr treatment with 1 microM RA,
      returning to a basal level by 24 hr. However, Northern blot analysis, performed
      concurrently, showed that RA progressively increased the steady-state osteopontin
      mRNA level beginning 2 hr before any increase in gene transcription and peaking
      at 24 hr. There was no difference in osteopontin mRNA stability between control
      and RA-treated cells after gene transcription was inhibited with 5,6-dichloro-1-D
      ribofuranosylbenzimidazole (DRB). Total RNA was obtained from cellular
      subfractions (nuclear matrix, nonmatrix chromatin, nuclear membrane, and
      cytoplasm) and reverse transcription-polymerase chain reaction (RT-PCR) performed
      with primers complementary to exons 3 and 4 of the mouse osteopontin gene.
      Unspliced PCR product, comprising the two exons and the intervening intron, was
      present in the nuclear matrix fractions of control and RA-treated cells. However,
      RA resulted in a time-dependent accumulation of mature osteopontin mRNA in all
      cellular subfractions, suggesting that the proficiency of nuclear processing of
      primary mRNA transcripts was greatly enhanced by RA. This action depended on de
      novo protein synthesis. These results demonstrate that the posttranscriptional
      action of RA is not unique to the regulation of alkaline phosphatase gene
      expression.

PMID- 9618140
TI  - Evidence for the participation of nerve growth factor and its low-affinity
      receptor (p75NTR) in the regulation of the myogenic program.
AB  - We have studied expression and function of neurotrophins and their receptors
      during myogenic differentiation of C2C12 cells, a clonal cell line derived from
      mouse muscle that is capable of in vitro differentiation. The genes coding for
      nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and their
      common low-affinity receptor p75(neurotrophin receptor) (p75NTR) were shown to be
      expressed in C2C12 myoblasts and downregulated during myogenic differentiation
      and fusion into myotubes. Cocultures with dorsal root ganglia from day 8 chick
      embryos revealed neurite-promoting activities of C2C12 cells that ceased with
      myogenic differentiation. These data suggest a temporal and developmental window
      for the effect of myogenic cell-derived neurotrophins on neuronal as well as on
      myogenic cell populations. NGF was shown to increase DNA synthesis and cell
      growth of C2C12 myoblasts and to enhance myogenic differentiation in this cell
      line. We present evidence that NGF-mediated processes take place at stages
      preceding myogenic differentiation. Enhanced muscle differentiation was also seen
      in p75NTR-overexpressing C2C12 myoblasts which maintained high levels of
      receptors but ceased to produce NGF during differentiation. In contrast, when
      exogenous NGF was present at the onset of myogenic differentiation of receptor
      overexpressing cells, muscle cell development was strongly repressed. This
      indicates that downregulation of p75NTR is necessary for guiding myogenic cells
      towards terminal differentiation. Since none of the trk high-affinity
      neurotrophin receptors could be demonstrated in C2C12 cells, we conclude that NGF
      mediates its nonneurotrophic effect via its low-affinity receptor in an autocrine
      fashion.

PMID- 9618141
TI  - Regulation of nerve growth factor and its low-affinity receptor (p75NTR) during
      myogenic differentiation.
AB  - In our preceding report, we have shown that nerve growth factor (NGF) and its low
      affinity receptor (p75NTR) are expressed in C2C12 myoblasts and downregulated
      during myogenic differentiation. Furthermore, NGF affects myogenic
      differentiation and cell growth via p75NTR and downregulation of p75NTR is
      essential for myogenic differentiation (Seidl et al., 1998). Here we show that
      NGF and p75NTR are regulated by mechanisms preceding terminal differentiation in
      myogenic cells. These mechanisms include cell-density phenomena such as cell-cell
      contact as well as signaling of basic fibroblast growth factor (FGF-2) and its
      receptor (FGFR1). Downregulation of NGF and p75NTR occurred as a consequence of
      increasing cell density, an important trigger for the onset of myogenic
      differentiation. FGF-2 and FGFR1 were shown to be present in C2C12 cells and
      exogenous FGF-2 induced NGF and p75NTR expression, implying that FGF/FGFR
      signaling is an upstream regulator of the NGF/p75NTR system. The fact that FGF-2
      could suspend yet not abolish density-induced downregulation indicates that cell
      cell contact counteracts the FGF effect and ultimately terminates NGF/p75NTR
      signaling. This evidence, together with the observation that p75NTR expression is
      suppressed in muscle progenitors, which constitutively express adenovirus E1A
      proteins and thus lack the competence of myogenic differentiation, underline the
      important role for the NGF/p75NTR system in the interplay of multiple factors and
      biological systems that balance myogenic differentiation at the appropriate
      spatial and temporal level.

PMID- 9618142
TI  - Effect of aging on EGF-stimulated replication of specific genes in rat
      hepatocytes.
AB  - EGF-stimulated replication of specific genes was examined in primary hepatocyte
      cultures from mature (6 months) and senescent (24 months) rats. Basal and EGF
      stimulated [3H]thymidine incorporation and DNA polymerase alpha activities, as
      well as total cellular DNA, were also assessed. The genes examined were
      dihydrofolate reductase (DHFR) and c-myc, as well as total mitochondrial DNA (mt
      DNA). Although [3H]thymidine incorporation, DNA polymerase alpha activity, total
      cellular DNA, DHFR, and c-myc gene specific DNA replication stimulated by EGF are
      reduced with age, mt DNA replication is not affected by either EGF or age.
      Chromosomal DNA replication is mediated mainly by DNA polymerase alpha while mt
      DNA replication is mediated by its own DNA polymerase gamma. Thus, the age
      related decline in stimulated DNA replication appears to be associated mainly
      with the DNA polymerase alpha activation pathway.

PMID- 9618143
TI  - Inhibition of the cytotoxicity of protein toxins by a novel plant metabolite,
      mansonone-D.
AB  - We have studied the effect of several structurally related mansonones on the
      cytotoxicity of plant and bacterial toxins in Vero and BER-40, a brefeldin A
      resistant mutant of Vero cells. Mansonone-D (MD), a sesquiterpenoid ortho
      naphthoquinone, inhibited the cytotoxicity of ricin, modeccin, Pseudomonas toxin,
      and diphtheria toxin in Vero cells to different extents. The inhibition of ricin
      cytotoxicity was dose dependent and reversed upon removal of the drug. Protection
      of ricin cytotoxicity was also observed in the presence of cycloheximide,
      indicating that de novo protein synthesis is not required for the protective
      effect. Although MD inhibited the degradation and excretion of ricin, the binding
      and internalization of ricin was not affected. In contrast, MD strongly reduced
      the specific binding of diphtheria toxin in Vero cells. Fluorescence microscopic
      studies show that MD treatment dramatically alters the morphology of the Golgi
      apparatus in Vero cells. The kinetic studies reveal that the protection of ricin
      cytotoxicity is the consequence of decreased toxin translocation to the cytosol
      in MD-treated cells. The reactive ortho-quinone moiety of MD is important for the
      protective effect as thespesone, a para-naphthoquinone with a heterocyclic ring
      structure identical to that of MD, did not inhibit the cytotoxicity of toxins.
      Thespone, a dehydromansonone-D, lacking two hydrogens from the heterocyclic
      dihydrofuran ring of MD, inhibited the cytotoxicity of ricin, but was albeit less
      potent than MD. Neither mansonone-E nor mansonone-H with reactive ortho-quinone
      moiety, but with a different heterocyclic structure, had any effect on the
      cytotoxicity of ricin indicating that the protective effect of MD is specifically
      related to the overall structure of the metabolite.

PMID- 9618144
TI  - Adenylyl cyclase activity and gene expression during mesodermal differentiation
      of the P19 embryonal carcinoma cells.
AB  - DMSO-primed P19 pluripotent cells, which recapitulate the first stages of
      mammalian cardiogenesis and endodermal formation, were used as an in vitro model
      to analyze the variations in activity and expression of the different adenylyl
      cyclase (AC) isoforms during the early events of embryonic cell differentiation.
      Here, we show that the total AC activity, which increases up to 10-fold after
      differentiation of P19 cells, is mainly associated with increases in AC2, AC5,
      and AC6 mRNA levels. Particularly, the marked increase in AC5 mRNA correlates
      with the appearance of beating cardiomyocytes and with the transcription of the
      atrial myosin light chain (MLC1A) gene which encodes a protein specifically
      involved in the cardiac muscle cell contractile phenotype. Together, the results
      strongly suggest that 1) a rise in cyclic AMP (cAMP) may be associated with
      cardiomyocyte and endodermal cell differentiation during mammalian embryogenesis;
      and 2) AC5 gene expression starts very early during normal mouse cardiogenesis
      and correlates with the differentiation of cardiomyocytes.

PMID- 9618145
TI  - Phenotypic and functional comparison of cultures of marrow-derived mesenchymal
      stem cells (MSCs) and stromal cells.
AB  - Mesenchymal stem cells (MSCs) are a population of pluripotent cells within the
      bone marrow microenvironment defined by their ability to differentiate into cells
      of the osteogenic, chondrogenic, tendonogenic, adipogenic, and myogenic lineages.
      We have developed methodologies to isolate and culture-expand MSCs from human
      bone marrow, and in this study, we examined the MSC's role as a stromal cell
      precursor capable of supporting hematopoietic differentiation in vitro. We
      examined the morphology, phenotype, and in vitro function of cultures of MSCs and
      traditional marrow-derived stromal cells (MDSCs) from the same marrow sample.
      MSCs are morphologically distinct from MDSC cultures, and flow cytometric
      analyses show that MSCs are a homogeneous cell population devoid of hematopoietic
      cells. RT-PCR analysis of cytokine and growth factor mRNA in MSCs and MDSCs
      revealed a very similar pattern of mRNAs including IL-6, -7, -8, -11, -12, -14,
      and -15, M-CSF, Flt-3 ligand, and SCF. Steady-state levels of IL-11 and IL-12
      mRNA were found to be greater in MSCs. Addition of IL-1alpha induced steady-state
      levels of G-CSF and GM-CSF mRNA in both cell preparations. In contrast, IL-1alpha
      induced IL-1alpha and LIF mRNA levels only in MSCs, further emphasizing
      phenotypic differences between MSCs and MDSCs. In long-term bone marrow culture
      (LTBMC), MSCs maintained the hematopoietic differentiation of CD34+ hematopoietic
      progenitor cells. Together, these data suggest that MSCs represent an important
      cellular component of the bone marrow microenvironment.

PMID- 9618146
TI  - Phenotypic consequences of transforming growth factor beta1 gene ablation in
      murine embryonic fibroblasts: autocrine control of cell proliferation and
      extracellular matrix biosynthesis.
AB  - The profound effects of transforming growth factor beta1 (TGF-beta1) on the
      immune system, cardiogenesis, in yolk sac hematopoeisis and in differentiation of
      endothelium have been demonstrated by detailed analyses of TGF-beta1 knockout
      mice during embryogenesis. We have systematically examined the autocrine and
      paracrine roles of TGF-beta1 in cell proliferation and in its ability to modulate
      the gene expression of selected components of extracellular matrix (ECM) using
      embryonic fibroblasts from TGF-beta1 null mice (TGF-beta-1(-/-)). The rates of
      cell proliferation of embryonic fibroblasts from normal mice (TGF-beta1(+/+)) and
      TGF-beta1 null mice were compared by cell counting, by 3H thymidine
      incorporation, and by measuring the fraction of cells in the G1, S, and G2/M
      phases of the cell cycle by fluorescent activated cell sorting (FACS).
      Concurrently, the expression of pro-alpha1(I) collagen, fibronectin, and
      plasminogen activator inhibitor-1 (PAI-1) was also quantified by hybridization of
      total mRNA from TGF-beta1(+/+) and TGF-beta1(-/-) embryonic fibroblasts. We
      report that TGF-beta1(-/-) cells proliferated at about twice the rate of TGF
      beta1(+/+) cells. Further, TGF-beta1 null fibroblasts accumulated and synthesized
      lower constitutive levels of pro-alpha1(I) collagen, fibronectin, and PAI-1 mRNA.
      The quantitative differences in the rates of cell proliferation and ECM gene
      expression between TGF-beta1(+/-) and TGF-beta1(-/-) cells could be eliminated by
      treatment of TGF-beta1(+/+) cells with a neutralizing antibody of TGF-beta1.
      Thus, our results are consistent with the hypothesis that TGF-beta1 acts as a
      negative autocrine regulator of growth and a positive autocrine regulator of ECM
      biosynthesis in embryonic fibroblasts.

PMID- 9618147
TI  - Epithelial permeability induced by neutrophil transmigration is potentiated by
      hypoxia: role of intracellular cAMP.
AB  - Mucosal tissues, such as the lung and intestine, are primary targets for ischemic
      damage. Under these conditions, neutrophil (polymorphonuclear leukocyte; PMN)
      infiltration into the protective epithelium has been implicated as a
      pathophysiologic mediator. Because PMN transepithelial migration results in
      increased paracellular permeability, and because our previous data revealed that
      epithelial hypoxia enhances PMN transmigration, we hypothesized that
      macromolecular permeability may be altered in epithelium exposed to hypoxia and
      reoxygenation (H/R) in the presence of PMNs. Human intestinal epithelia (T84)
      were grown on permeable supports, exposed to cellular hypoxia (pO2 20 torr) for 0
      72 hr, and examined for increases in PMN-evoked permeability by using standard
      flux assays. Increasing epithelial hypoxia potentiated PMN-induced permeability
      of labeled paracellular tracers (size range 3-500 kD). Such increases were
      blocked by monoclonal antibody (mAb) to the PMN integrin CD11b (82 +/- 1%
      decreased compared with control mAb) and were partially blocked by anti-CD47 mAb
      (51 +/- 1%). Assessment of barrier recovery revealed that monolayers exposed to
      H/R were significantly diminished in their ability to reseal following PMN
      transmigration (recovery of 36 +/- 6% in H/R vs. 94 +/- 2% in normoxic controls).
      Because intracellular cyclic AMP (cAMP) has been demonstrated to regulate
      epithelial permeability, and because PMN-derived compound(s), (i.e., 5'-adenosine
      monophosphate; AMP) elevate epithelial cAMP, we examined the impact of hypoxia on
      epithelial cAMP responses. These experiments revealed that hypoxic epithelia were
      diminished in their ability to generate cAMP, and pharmacologic elevation (8
      bromo-cAMP) of intracellular cAMP in hypoxic cells normalized both PMN-induced
      permeability changes and restoration of barrier function. These results support a
      role for PMN in increased intestinal permeability associated with reperfusion
      injury and imply a substantial role for cAMP signaling in maintenance of
      permeability during PMN transmigration.

PMID- 9618148
TI  - Glucocorticoid stimulation of Na+-dependent ascorbic acid transport in osteoblast
      like cells.
AB  - Ascorbic acid (AA) is an essential cofactor for osteoblast differentiation both
      in vivo and in vitro. Before it can function, this vitamin must be transported
      into cells via a specific Na+-dependent AA transporter. In this study, we examine
      the regulation of this transport activity by glucocorticoids, a class of steroid
      hormones known to stimulate in vitro osteoblast differentiation. Dexamethasone
      stimulated Na+-dependent AA transport activity approximately twofold in primary
      rat calvarial osteoblasts. Effects of hormone on ascorbic acid transport were
      rapid (detected within 24 h) and were maximally stimulated by 25-50 nM
      dexamethasone. Similar effects of dexamethasone on transport activity were also
      observed in murine MC3T3-E1 cells. This preosteoblast cell line was used for a
      more detailed characterization of the glucocorticoid response. Transport activity
      was stimulated selectively by glucocorticoids (dexamethasone > corticosterone)
      relative to other steroid hormones (progesterone and 17-beta-estradiol) and was
      blocked when cells were cultured in the presence of cycloheximide, a protein
      synthesis inhibitor. Kinetic analysis of AA transporter activity in control and
      dexamethasone-treated cells indicated a Km of approximately 17 microM for both
      groups. In contrast, dexamethasone increased Vmax by approximately 2.5-fold.
      Cells also contained an Na+-independent glucose transport activity that has been
      reported in other systems to transport vitamin C as oxidized dehydroascorbic
      acid. In marked contrast to Na+-dependent AA transport, this activity was
      inhibited by dexamethasone. Thus, glucocorticoids increase Na+-dependent AA
      transport in osteoblasts, possibly via up-regulation of transporter synthesis,
      and this response can be resolved from actions of glucocorticoids on glucose
      transport.

PMID- 9618149
TI  - Reduced viability of human vascular endothelial cells cultured on Matrigel.
AB  - Optimal vascular homeostasis requires efficient control of both proliferation and
      elimination of vascular endothelial cells. Programmed cell death, or apoptosis,
      is the main mechanism controlling cell elimination, and it is an essential
      component of vascular formation. Human vascular endothelial cells die in vitro,
      if prevented from obligatory survival factors like growth factors or attachment
      and cell spreading, but very little is known about the mechanisms controlling
      endothelial cell elimination. Signaling from the extracellular matrix affects the
      behavior and functions of human umbilical vein endothelial cells (HUVECs), and we
      have recently demonstrated the beneficial effects of plating on the reconstituted
      extracellular matrix Matrigel, on the inducible nitric oxide production of
      freshly isolated HUVECs. In this work we observed that cultured HUVECs formed
      typical capillary-like structures on Matrigel, but unexpectedly, after 24-48
      hours their viability was gradually lost. Viability was measured with an assay
      based on mitochondrial reduction of reagent XTT. No decrease in viability was
      seen in freshly isolated HUVECs or in cultured fibroblasts during this time. It
      is known that cells often turn into apoptosis if they receive conflicting
      information from their surroundings, and apparently signaling from Matrigel to
      HUVECs, while at their in vitro proliferating phenotype, resulted in launching of
      the apoptotic machinery. Thus, proliferating and differentiated phenotypes of
      endothelial cells seemed to have different sensitivity to signals that induce
      apoptosis.

PMID- 9618150
TI  - Inhibition of PI 3-kinase and RAS blocks IGF-I and insulin-induced uncoupling
      protein 1 gene expression in brown adipocytes.
AB  - Fetal brown adipocytes expressed uncoupling protein 1 (UCP1) mRNA, this
      expression being blunted throughout culture for 24 h in a serum-free medium. At
      physiological doses, either insulin-like growth factor I (IGF-I) or insulin
      turned out to be as potent as dibutyryl cAMP (dbcAMP) in increasing UCP1 gene
      transcription rate (1 h) and also UCP1 mRNA accumulation (3 h), their maximal
      effect (15-fold increase) reached upon treatment for 24 h. Upon treatment with
      either IGF-I or insulin for 48 h, a 7-fold increase in the UCP1 protein content
      relative to levels in the control cells was found, this induction being abolished
      in the presence of cycloheximide. Moreover, either IGF-I or insulin
      transactivates the UCP1-chloramphenicol acetyl transferase (CAT) fusion gene
      after transient transfection of primary brown adipocytes, these effects being
      tissue-specific. Transient transfection of dominant-negative form of
      phosphatidylinositol (PI) 3-kinase completely blocked the transactivation of the
      fusion gene UCP1-CAT induced by either IGF-I or insulin, although inhibition of
      p70S6kinase with rapamycin does not preclude transactivation of the UCP1 promoter
      by insulin. Furthermore, transient transfection of dominant-negative form of p21
      ras or treatment of cells with a mitogen-activated protein kinase kinase (MEK-1)
      inhibitor (PD098059) completely abolished insulin-induced UCP1-CAT
      transactivation. Cotransfection with dominant-negative p85 or with dominant
      negative Ras also produced down-regulation of the insulin or IGF-I-induced 12-O
      tetradecanoylphorbol-13-acetate response element (TRE)-CAT (five AP-1, activating
      protein-1, binding sites arranged in tandem) transactivation. In addition,
      insulin induced AP-1 DNA binding activity, this effect being totally prevented in
      the presence of MEK-1 inhibitor. These results strongly suggest that either IGF-I
      or insulin induced thermogenic-differentiation through AP-1 activity in a PI 3
      kinase and Ras/MAPK dependent manner in brown adipocytes.

PMID- 9618151
TI  - Characterization of the expression and steroid hormone control of sialomucin
      complex in the rat uterus: implications for uterine receptivity.
AB  - The sialomucin complex (SMC), originally isolated as a heterodimeric glycoprotein
      complex from membranes of ascites sublines of a highly metastatic mammary
      adenocarcinoma, consists of a high Mr mucin subunit (ASGP-1, ascites
      sialoglycoprotein) and a transmembrane subunit (ASGP-2) with two epidermal growth
      factor-like domains. SMC has been characterized in the mammary gland, where it is
      present in both membrane and nonmembrane (soluble) forms, the latter lacking its
      transmembrane domain. SMC in the mammary gland is observed during pregnancy and
      lactation, but not in the virgin gland, and is regulated by a posttranscriptional
      mechanism. Both membrane and nonmembrane forms of SMC are found in rat uterus,
      also as a complex of ASGP-1 and ASGP-2. Immunocytochemical analyses indicate that
      the primary site of expression is at the luminal surface of the endometrium.
      Approximately 40% of the SMC, corresponding to the nonmembrane fraction, is
      removed by rinsing uterine preparations with saline, indicating that the soluble
      form is adsorbed loosely to the cell surface. In contrast to mammary gland, SMC
      is most highly expressed in the virgin animal, and its expression varies during
      the estrous cycle with the steady state level of transcript. The complex is
      present in a location consistent with steric inhibition of blastocyst
      implantation and is abruptly lost at the beginning of the period of receptivity
      for implantation. Expression of SMC in the uterus is regulated by estrogen and
      progesterone and is inversely correlated with receptivity. Both implantation and
      loss of SMC expression can be blocked with RU486. We propose that the down
      regulation of SMC and its loss from the apical surface of the rat uterine lining
      contribute to the generation of the receptive state for uterine implantation.
      Furthermore, the presence of both membrane and soluble SMC at the luminal surface
      of the endometrium may provide a model for its proposed protective function in
      other accessible and vulnerable epithelia.

PMID- 9618152
TI  - Effects of interferon gamma on growth, apoptosis, and MHC class II expression of
      immature rat intestinal crypt (IEC-6) cells.
AB  - Intestinal epithelial cells and the mucosal immune cells in close proximity are
      thought to interact very closely. One well-established mechanism of this
      intercellular cross-talk is via the production of cytokines such as interferon
      gamma (IFNgamma). The aim of this study was to analyze the effects of IFNgamma on
      intestinal crypt epithelial cells. IEC-6 cells were cultured in the presence or
      absence of IFNgamma to measure its effects on proliferation, cell cycle,
      apoptosis, and major histocompatibility complex (MHC) class II antigen
      expression. Even at very low doses (0.01 U/ml), IFNgamma significantly inhibited
      IEC-6 cell proliferation, as demonstrated by reduced 3H-thymidine uptake, stable
      cell count, and complete arrest in the quiescent G0/G1 phase of the cell cycle.
      Incubation with supraphysiological doses of IFNgamma (100-1,000 U/ml) did not
      induce apoptosis, as assessed by morphology and the TUNEL assay. IFNgamma
      significantly induced de novo IEC-6 class II antigen expression. Tumor necrosis
      factor alpha (TNF alpha), which alone had no effect, synergistically enhanced
      this effect of IFNgamma. MHC class II antigen expression was observed to be
      independent of cell cycle phase. Our results indicate that IFNgamma alters
      immature crypt epithelial cell turnover and upregulates MHC class II expression.
      These alterations may be important in the pathogenesis of immune-mediated bowel
      disorders.

PMID- 9618153
TI  - Antagonistic regulation of cell migration by epidermal growth factor and
      glucocorticoid in human gastric carcinoma cells.
AB  - Epidermal growth factor (EGF) induced the disruption and scattering of colonies
      of TMK-1, a cell line derived from a human gastric carcinoma. A stimulatory
      action of EGF on cell migration was also observed as determined by a wound assay.
      However, these actions of EGF were inhibited if the cells were pretreated with
      dexamethasone, a synthetic glucocorticoid. Dexamethasone increased cell adhesion
      to collagen type IV and laminin, but not to poly-L-lysine and fibronectin. In
      contrast, EGF did not affect cell adhesion to these extracellular matrices
      whether dexamethasone was present or not. Dexamethasone enhanced the protein
      levels of both alpha1 and beta1 integrin subunits, and that of the alpha1 beta1
      heterodimer. Further, flow cytometric analysis revealed that dexamethasone
      increased the expression of beta1 and alpha1 integrin subunits at the cell
      surface, whereas EGF increased expression of beta1 and alpha2 subunits at the
      cell surface. Antibodies against alpha1 and beta1 integrin subunits inhibited the
      increased cell adhesion seen in the presence of dexamethasone. An
      immunofluorescence study indicated that dexamethasone increased the formation of
      focal adhesions along the entire edges of cell colonies. In contrast, EGF led to
      the formation of focal adhesions preferentially at the cell front, and this EGF
      induced preferential formation was not observed if the cells were pretreated with
      dexamethasone. These results suggest that glucocorticoid increased cell adhesion
      to the extracellular matrix via alpha1 beta1 integrin, and thereby antagonized
      EGF-induced cell migration.

PMID- 9618154
TI  - Decreased mitochondrial function in quiescent cells isolated from multicellular
      tumor spheroids.
AB  - Cells in the inner region of multicellular spheroids markedly reduce their oxygen
      consumption rate, presumably in response to their stressful microenvironment. To
      determine the mechanism behind this metabolic adaptation, we have investigated
      relative mitochondrial mass and mitochondrial function in cells isolated from
      different regions of tumor spheroids by using a combination of mitochondrial
      specific fluorescent stains and flow cytometric analysis. Uptake of rhodamine 123
      (R123) is driven by the mitochondrial membrane potential and thus reflects
      mitochondrial activity. Uptake of 10-nonyl-acridine orange (NAO) reflects total
      mitochondrial mass independently of activity because this compound binds to
      cardiolipin in the inner mitochondrial membrane. NAO fluorescence per unit cell
      volume only decreased 10-20% for cells from the inner spheroid region compared
      with those near the surface. There was greater than a twofold reduction in R123
      fluorescence in the inner region cells, however. Thus, tumor cells in spheroids
      alter their rate of respiration predominately by downregulating mitochondrial
      function as opposed to degradation of mitochondria. There was a correlation
      between R123 staining per unit cell volume and the growth fraction of the cells
      from spheroids, but not for monolayer cultures. We also show a linear correlation
      between R123 staining and the rate of oxygen consumption for both monolayer- and
      spheroid-derived cells. After separating the inner region cells from the spheroid
      and replating them in monolayer culture, the R123 uptake recovered to normal
      levels prior to entry of the cells into S-phase. This reduction in mitochondrial
      function in quiescent cells from spheroids can explain the long period required
      for these cells to re-enter the cell cycle and may have important implications
      for the regulation of tumor cell oxygenation in vivo.

PMID- 9618155
TI  - Regulation of TNF-alpha-induced reorganization of the actin cytoskeleton and cell
      cell junctions by Rho, Rac, and Cdc42 in human endothelial cells.
AB  - We have investigated the role of the small guanosine-trisphosphate (GTP)-binding
      proteins, Rho, Rac, and Cdc42, in the early responses of human umbilical vein
      endothelial cells (HUVECs) to TNF-alpha (tumor necrosis factor-alpha). Quiescent
      confluent HUVECs incubated with TNF-alpha for 5-30 min showed an increased
      formation of membrane ruffles, filopodia, and actin stress fibres followed by
      cell retraction and formation of intercellular gaps. This process was accompanied
      by the dispersion of cadherin-5 from intercellular junctions. TNF-alpha also
      induced a transient increase in polymerized F-actin, as determined both by
      measuring G-actin content and by quantifying fluorescent emission from
      fluorescein isothiocyanate (FITC)-phalloidin-labelled F-actin. Microinjection of
      cells with activated RhoA protein led to an increase in polymerized actin,
      formation of stress fibres, cell retraction as well as dispersion of cadherin-5.
      The proteins Cdc42 and Rac induced qualitatively similar effects to Rho, although
      not as dramatic and in addition induced formation of filopodia and lamellipodia.
      Microinjection of cells with a Rho inhibitor, C3 transferase, prevented gap
      formation caused by TNF-alpha. Similar effects were observed in cells
      microinjected with the dominant inhibitory proteins N17Cdc42 and N17Rac1. Cell
      retraction and gap formation were also prevented by inhibitors of myosin light
      chain kinase (MLCK). Our data suggest that Cdc42, Rac, and Rho are activated in a
      hierarchical cascade following stimulation with TNF-alpha leading to actomyosin
      mediated cell retraction and formation of intercellular gaps.

PMID- 9618156
TI  - Determinants of glutamine dependence and utilization by normal and tumor-derived
      breast cell lines.
AB  - A continual supply of the amino acid glutamine (GLN) may be necessary for
      cancerous cell growth. GLN plays a central role in multiple metabolic pathways
      and has long been considered an essential component of tissue culture media.
      However, the GLN requirements of tumor cell lines and the factors that determine
      a cell's need for GLN have not been comprehensively studied. Also, it remains
      unclear how various metabolic pathways contribute to GLN consumption. In the
      present study, possible determinants of GLN metabolism were examined in seven
      breast cell lines, two derived from immortalized normal tissue and five of tumor
      origin. These cells exhibited different dependencies on media GLN concentration
      for growth and a wide range of GLN utilization rates. GLN uptake was facilitated
      by a single, common transporter functionally defined as System ASC. However, the
      affinities for GLN exhibited by this transporter differed appreciably between
      cell lines. Furthermore, the concentration at which media GLN became a limiting
      factor for cellular proliferation correlated with transporter affinity. The
      origin of the cell lines was not a determinant of GLN metabolism because
      immortalized cells of nontumor origin exhibited GLN dependence and utilization
      rates comparable to those of tumor-derived cells. The rates of CO2 production
      from GLN were similar for each cell lines. Rates of GLN disappearance and
      glutamate appearance in media were strongly correlated, with 32-80% of media GLN
      converted to glutamate. Both rates were directly affected by media cystine
      concentration, suggesting that a large portion of glutamate efflux was coupled
      with cystine import through the amino acid transport system x(c)-. These results
      demonstrated that cell growth is a function of GLN influx and suggest that GLN is
      used to supply glutamate and cystine, perhaps for glutathione synthesis.

PMID- 9618157
TI  - Casein kinase 2 phosphorylation of recombinant rat osteopontin enhances adhesion
      of osteoclasts but not osteoblasts.
AB  - Osteopontin (OP) is a highly phosphorylated bone matrix protein and contains the
      RGD cell-binding motif, which mediates cell adhesion through integrin receptors
      that include alpha(v)beta3. Casein kinase 2 (CK2) is a factor-independent
      serine/threonine kinase, which may be the predominant physiologically relevant
      kinase for OP phosphorylation. This study was designed to examine the effects of
      unphosphorylated recombinant rat OP, and CK2-phosphorylated OP (P-OP), on the
      adhesion and function of mouse osteoclasts (OC) and osteoblast-like cells (UMR
      201-10B and UMR 106-06) in vitro. OP significantly increased OC adhesion compared
      to plastic alone, and cell attachment was further increased at least twofold on
      OP phosphorylated with CK2. Attachment was dependent on the integrity of the RGD
      domain and was completely abolished in the presence of 1 mM RGD peptide. Neither
      CK2 phosphorylation of mutant OP, in which the RGD was converted to RGE or RAD,
      nor protein kinase C (PKC) phosphorylation of wild-type OP enhanced OC
      attachment. An antibody to the beta3 integrin subunit, but not anti-mouse CD44
      antibody, specifically blocked the proportion of attachment due to
      phosphorylation of OP. Actin ring formation in OC was increased by plating cells
      onto OP, with no further increase by phosphorylation. Both OP and CK2
      phosphorylated OP enhanced attachment of the two osteoblastic cell lines,
      compared to plastic, but in contrast to OCs, there was no significant difference
      with phosphorylation. Osteoblast attachment was totally blocked by 1 mM RGD
      peptide, but was not influenced by the beta3 integrin antibody. Plating of UMR
      201-10B cells onto OP further increased retinoic acid-induced alkaline
      phosphatase expression. The results suggest that specific phosphorylation of OP
      is important for interaction with OCs, compared with osteoblastic cells, and that
      alternative integrins may be important in the interaction between osteoblastic
      cells and OP compared with OCs.

PMID- 9618158
TI  - Manganese enhances phosphorylation of a 47 kD protein in retinoic acid-induced HL
      60 cells.
AB  - We previously observed that HL-60 cells treated with manganese (Mn) during
      differentiation displayed an enhanced oxidative burst. Since a Mn-dependent
      kinase has been identified and phosphorylation is involved in burst activation,
      the objective of this research was to identify proteins in retinoic acid-induced
      HL-60 cells whose phosphorylation after phorbol myristate acetate (PMA)
      stimulation was affected by Mn treatment. Cells received Mn during
      differentiation and were then harvested, labeled with [32]P-orthophosphate, and
      stimulated with PMA. Cytosolic proteins were separated by isoelectric focusing,
      SDS-PAGE, and two-dimensional (2-D) gel electrophoresis. Time studies showed that
      Mn treatment did not alter the rate of PMA activated phosphorylation. Isoelectric
      focusing revealed that PMA stimulation resulted in the appearance of three
      phosphoproteins at pI's of 6.8, 7.3, and 7.8. Size separation gels showed a 200%
      increase in phosphorylation of a 47 kD protein in Mn-treated cells after
      stimulation. The 2-D gels showed that the pI of this protein was 6.8. Therefore,
      Mn treatment resulted in greater phosphorylation of a 47 kD protein, pI 6.8, in
      phorbol ester-stimulated cells.

PMID- 9618159
TI  - Distinct regulation of pHin and [Ca2+]in in human melanoma cells with different
      metastatic potential.
AB  - We investigated whether alterations in the mechanisms involved in intracellular
      pH (pHin) and intracellular calcium ([Ca2+]in) homeostasis are associated with
      the metastatic potential of poorly (A375P) and highly (C8161) metastatic human
      melanoma cells. We monitored pHin and [Ca2+]in simultaneously, using the
      fluorescence of SNARF-1 and Fura-2, respectively. Our results indicated that
      steady-state pHin and [Ca2+]in between these cell types were not significantly
      different. Treatment of cells with NH4Cl resulted in larger pHin increases in
      highly than in poorly metastatic cells, suggesting that C8161 cells have a lower
      H+ buffering capacity than A375P. NH4Cl treatment also increased [Ca2+]in only in
      C8161 cells. To determine if the changes in [Ca2+]in triggered by NH4Cl treatment
      were due to alterations in either H+- or Ca2+-buffering capacity, cells were
      treated with the Ca2+-ionophore 4Br-A23187, to alter [Ca2+]in. The magnitude of
      the ionophore-induced [Ca2+]in increase was slightly greater in C8161 cells than
      in A375P. Moreover, A375P cells recover from the ionophore-induced [Ca2+]in load,
      whereas C8161 cells did not, suggesting that A375P may exhibit distinct [Ca2+]in
      regulatory mechanisms than C8161 cells, to recover from Ca2+ loads. Removal of
      extracellular Ca2+ ([Ca2+]ex) decreased [Ca2+]in in both cell types at the same
      extent. Ionophore treatment in the absence of [Ca2+]ex transiently increased
      [Ca2+]in in C8161, but not in A375P cells. Endoplasmic reticulum (ER) Ca2+-ATPase
      inhibitors such as cyclopiazonic acid (CPA) and thapsigargin (TG) increased
      steady-state [Ca2+]in only in C8161 cells. Together, these data suggest that the
      contribution of intracellular Ca2+ stores for [Ca2+]in homeostasis is greater in
      highly than in poorly metastatic cells. Bafilomycin treatment, to inhibit V-type
      H+-ATPases, corroborated our previous results that V-H+-ATPases are functionally
      expressed at the plasma membranes of highly metastatic, but not in poorly
      metastatic cells (Martinez-Zaguilan et al., 1993). Collectively, these data
      suggest that distinct pHin and [Ca2+]in regulatory mechanisms are present in
      poorly and highly metastatic human melanoma cells.

PMID- 9618160
TI  - CD44v(3,8-10) is involved in cytoskeleton-mediated tumor cell migration and
      matrix metalloproteinase (MMP-9) association in metastatic breast cancer cells.
AB  - In the present study, we have employed a unique breast cancer cell line (Met-1,
      which was derived from a high metastatic potential tumor in transgenic mice
      expressing polyomavirus middle T oncogene) to study the role of CD44 variant
      isoform(s) in the regulation of metastatic breast tumor cell behavior. The
      results of reverse transcriptase-polymerase chain reaction, Southern blot,
      nucleotide sequencing, immunoprecipitation, and immunoblot analyses indicated
      that these cells express a major CD44 isoform (molecular weight approximately 260
      kDa) containing a v3,8-10 exon insertion (designated as CD44v3,8-10). In
      addition, we have determined that CD44v3,8-10 binds specifically to the
      cytoskeletal proteins such as ankyrin. Biochemical analyses, using competition
      binding assays and a synthetic peptide identical to NGGNGTVEDRKPSEL (a sequence
      located between aa480 and aa494 of CD44v3,8-10) indicate that this 15-amino acid
      peptide binds specifically to the cytoskeletal protein ankyrin (but not to fodrin
      or spectrin). This peptide competes effectively for ankyrin binding to CD44v3,8
      10. Therefore, we believe that the sequence 480NGGNGTVEDRKPSE494L, located at the
      cytoplasmic domain of CD44v3,8-10, is required for the ankyrin binding. We have
      also detected that CD44v3,8-10-containing Met-1 cells are capable of forming
      membrane spikes or "invadopodia" structures and undergo active migration
      processes. Treatments of Met-1 cells with certain agents including anti-CD44v3
      antibody, cytochalasin D (a microfilament inhibitor), and W-7 (a calmodulin
      antagonist), but not colchicine (a microtubule disrupting agent) effectively
      inhibit "invadopodia" formation and subsequent tumor cell migration. Further
      analyses using zymography assays and double immunofluorescence staining indicated
      that CD44v3,8-10 is closely associated with the active form of matrix
      metalloproteinase, MMP-9, in a complex within "invadopodia" structures. These
      findings suggest that CD44v3,8-10 plays an important role in linking ankyrin to
      the membrane-associated actomyosin contractile system required for "invadopodia"
      formation (coupled with matrix degradation activities) and tumor cell migration
      during breast cancer progression.

PMID- 9618161
TI  - Primary cell cultures from murine kidney and heart differ in endosomal pH.
AB  - Endosomal and lysosomal pH values have been determined for many established
      cultured cell lines of different origins. These cell lines may be grouped into
      two classes based on observed differences in pH of early (recycling) endosomes.
      Members of the first class typically have an early endosomal pH of 6.2, whereas
      members of the second class typically have an early endosomal pH of 5.4. Because
      established cell lines may have developed artificial differences in endosomal pH
      due to extended culture, it remains to be determined if endosomal pH differences
      exist in vivo and whether they are functionally significant. To address this
      question, we generated adherent primary explants from mouse kidney (primarily
      epithelial cells) and heart (primarily fibroblasts and cardiac muscle cells).
      Interestingly, enhanced acidification was observed in heart cell endosomes (pH =
      5.5) compared with kidney cell endosomes (pH = 6.0). These results indicate that
      differences in endosomal pH do not solely arise from extended cell culture and
      imply that such differences may be important for the proper functioning of
      different cell types.

PMID- 9618162
TI  - doublecortin is the major gene causing X-linked subcortical laminar heterotopia
      (SCLH).
AB  - Subcortical laminar heterotopia (SCLH), or 'double cortex', is a cortical
      dysgenesis disorder associated with a defect in neuronal migration. Clinical
      manifestations are epilepsy and mental retardation. This disorder, which mainly
      affects females, can be inherited in a single pedigree with lissencephaly, a more
      severe disease which affects the male individuals. This clinical entity has been
      described as X-SCLH/LIS syndrome. Recently we have demonstrated that the
      doublecortin gene, which is localized on the X chromosome, is implicated in this
      disorder. We have now performed a systematic mutation analysis of doublecortin in
      11 unrelated females with SCLH (one familial and 10 sporadic cases) and have
      identified mutations in 10/11 cases. The sequence differences include nonsense,
      splice site and missense mutations and these were found throughout the gene.
      These results provide strong evidence that loss of function of doublecortin is
      the major cause of SCLH. The absence of phenotype-genotype correlations suggests
      that X-inactivation patterns of neuronal precursor cells are likely to contribute
      to the variable clinical severity of this disorder in females.

PMID- 9618163
TI  - WHSC1, a 90 kb SET domain-containing gene, expressed in early development and
      homologous to a Drosophila dysmorphy gene maps in the Wolf-Hirschhorn syndrome
      critical region and is fused to IgH in t(4;14) multiple myeloma.
AB  - Wolf-Hirschhorn syndrome (WHS) is a malformation syndrome associated with a
      hemizygous deletion of the distal short arm of chromosome 4 (4p16.3). The
      smallest region of overlap between WHS patients, the WHS critical region, has
      been confined to 165 kb, of which the complete sequence is known. We have
      identified and studied a 90 kb gene, designated as WHSC1 , mapping to the 165 kb
      WHS critical region. This 25 exon gene is expressed ubiquitously in early
      development and undergoes complex alternative splicing and differential
      polyadenylation. It encodes a 136 kDa protein containing four domains present in
      other developmental proteins: a PWWP domain, an HMG box, a SET domain also found
      in the Drosophila dysmorphy gene ash -encoded protein, and a PHD-type zinc
      finger. It is expressed preferentially in rapidly growing embryonic tissues, in a
      pattern corresponding to affected organs in WHS patients. The nature of the
      protein motifs, the expression pattern and its mapping to the critical region led
      us to propose WHSC1 as a good candidate gene to be responsible for many of the
      phenotypic features of WHS. Finally, as a serendipitous finding, of the t(4;14)
      (p16.3;q32.3) translocations recently described in multiple myelomas, at least
      three breakpoints merge the IgH and WHSC1 genes, potentially causing fusion
      proteins replacing WHSC1 exons 1-4 by the IgH 5'-VDJ moiety.

PMID- 9618164
TI  - Modification of splicing in the dystrophin gene in cultured Mdx muscle cells by
      antisense oligoribonucleotides.
AB  - Deletions and point mutations in the gene encoding the cytoskeletal protein
      dystrophin and its isoforms cause either the severe progressive myopathy Duchenne
      muscular dystrophy (DMD) or the milder Becker muscular dystrophy (BMD), largely
      depending on whether the reading frame is lost or maintained respectively.
      Frameshift mutations tend to result in a lack of dystrophin at the sarcolemma,
      destabilization of the membrane and degeneration of skeletal muscle. The mdx
      mouse is a valuable animal model of DMD as it bears a nonsense point mutation in
      exon 23 of the murine DMD gene leading to an absence of dystrophin expression in
      the muscle sarcolemma and muscular dystrophy. This report represents a novel
      approach to correct dystrophin deficiency at the post-transcriptional level by
      transfection of muscle cells with antisense RNA. Essentially, 2'- O -methyl
      oligoribonucleotides (2'OMeRNA) were delivered to the nuclei of primary mdx
      myoblasts in culture. Dystrophin expression was observed in the sarcolemma of
      transfected mdx myotubes after transfection by an oligonucleotide complementary
      to the 3' splice site of murine dystrophin intron 22. Direct sequencing of RT-PCR
      products from these cells revealed precise splicing of exon 22 to exon 30,
      skipping the mutant exon and creating a novel in-frame dystrophin transcript. As
      patients with comparable in-frame internal deletions show relatively mild
      myopathic symptoms, this may in the future offer a therapeutic approach for DMD,
      as well as for other inherited disorders.

PMID- 9618165
TI  - Loss-of-function mutations in the LIM-homeodomain gene, LMX1B, in nail-patella
      syndrome.
AB  - Nail-patella syndrome (NPS) is an inherited developmental disorder most commonly
      involving maldevelopment of the fingernails, kneecaps and elbow joints. NPS
      exhibits wide variation in phenotypic expression within and among families with
      respect to these features. Other skeletal abnormalities such as hip dislocation
      and club foot have also been reported in some individuals with NPS. There is an
      association between NPS and renal disease, and between NPS and open-angle
      glaucoma (OAG), but it is not known whether mutations in a single gene cause the
      observed skeletal, renal and ophthalmic abnormalities. Recently, LMX1B , a
      transcription factor of the LIM-homeodomain type with homologs that are important
      for limb development in vertebrates, was mapped to the same general location as
      NPS at 9q34. We sequenced a large segment of LMX1B from the genomic DNA of
      probands from four families with NPS and OAG, and identified four mutations: two
      stop codons, a deletion causing a frameshift and a missense mutation in a
      functionally important residue. The presence of these putative loss-of-function
      mutations in the DNA of individuals with NPS indicates that haploinsufficiency of
      LMX1B underlies this disorder. These findings help to explain the high degree of
      variability in the NPS phenotype, and suggest that the skeletal defects in NPS
      are a result of the diminished dorsoventral patterning activity of LMX1B protein
      during limb development. The results further suggest that the NPS and OAG
      phenotypes in the families studied result from mutations in a single gene, LMX1B.

PMID- 9618166
TI  - Two frequent missense mutations in Pendred syndrome.
AB  - Pendred syndrome is an autosomal recessive disorder characterized by early
      childhood deafness and goiter. A century after its recognition as a syndrome by
      Vaughan Pendred, the disease gene ( PDS ) was mapped to chromosome 7q22-q31.1
      and, recently, found to encode a putative sulfate transporter. We performed
      mutation analysis of the PDS gene in patients from 14 Pendred families
      originating from seven countries and identified all mutations. The mutations
      include three single base deletions, one splice site mutation and 10 missense
      mutations. One missense mutation (L236P) was found in a homozygous state in two
      consanguineous families and in a heterozygous state in five additional non
      consanguineous families. Another missense mutation (T416P) was found in a
      homozygous state in one family and in a heterozygous state in four families.
      Pendred patients in three non-consanguineous families were shown to be compound
      heterozygotes for L236P and T416P. In total, one or both of these mutations were
      found in nine of the 14 families analyzed. The identification of two frequent PDS
      mutations will facilitate the molecular diagnosis of Pendred syndrome.

PMID- 9618167
TI  - Molecular analysis of the PDS gene in Pendred syndrome.
AB  - Pendred syndrome is an autosomal recessive disorder characterized by the
      association between sensorineural hearing loss and thyroid swelling or goitre and
      is likely to be the most common form of syndromic deafness. Within the thyroid
      gland of affected individuals, iodide is incompletely organified with variable
      effects upon thyroid hormone biosynthesis, whilst the molecular basis of the
      hearing loss is unknown. The PDS gene has been identified by positional cloning
      of chromosome 7q31, within the Pendred syndrome critical linkage interval and
      encodes for a putative ion transporter called pendrin. We have investigated a
      cohort of 56 kindreds, all with features suggestive of a diagnosis of Pendred
      syndrome. Molecular analysis of the PDS gene identified 47 of the 60 (78%) mutant
      alleles in 31 families (includes three homozygous consanguineous kindreds and one
      extended family segregating three mutant alleles). Moreover, four recurrent
      mutations accounted for 35 (74%) of PDS disease chromosomes detected and
      haplotype analysis would favour common founders rather than mutational hotspots
      within the PDS gene. Whilst these findings demonstrate molecular heterogeneity
      for PDS mutations associated with Pendred syndrome, this study would support the
      use of molecular analysis of the PDS gene in the assessment of families with
      congenital hearing loss.

PMID- 9618168
TI  - Mutation in the RIEG1 gene in patients with iridogoniodysgenesis syndrome.
AB  - Axenfeld-Rieger syndrome (ARS) and iridogoniodysgenesis syndrome (IGDS) are
      clinically related autosomal dominant disorders which affect the anterior segment
      of the eye as well as non-ocular structures. ARS patients present with iris
      hypoplasia, a prominent Schwalbe line, adhesions between the iris stroma and the
      iridocorneal angle and increased intraocular pressure. IGDS is characterized by
      iris hypoplasia, goniodysgenesis and increased intraocular pressure. Each
      syndrome also presents with non-ocular features including maxillary hypoplasia,
      micro and anodontia, redundant periumbilical skin, hypospadius (in males), and
      each has been genetically linked to chromosome 4q25. RIEG1 , the gene responsible
      for the 4q25 ARS phenotype, recently has been cloned. RIEG1 encodes a novel
      member of the bicoid class of homeobox proteins known to be active as
      transcription factors. Mutational analysis has previously detected several
      mutations in this gene in ARS individuals. We have now detected a mutation in
      RIEG1 which segregates with the disease phenotype in a family with IGDS. This
      mutation is a G-->A transition altering an arginine residue to a histidine in a
      highly conserved location in the second helix of the homeobox of RIEG1. This
      mutation indicates that IGDS and ARS are allelic variants of the same disorder.
      This wide variability in clinical consequences of mutations at the RIEG1 4q25
      locus implicates the RIEG gene broadly in ocular and craniofacial disorders.

PMID- 9618169
TI  - Genetic heterogeneity in familial hyperinsulinism.
AB  - Familial hyperinsulinism (HI) is a disorder characterized by dysregulation of
      insulin secretion and profound hypoglycemia. Mutations in both the Kir6.2 and
      sulfonylurea receptor (SUR1) genes have been associated with the autosomal
      recessive form of this disorder. In this study, the spectrum and frequency of
      SUR1 mutations in HI and their significance to clinical manifestations of the
      disease were investigated by screening 45 HI probands of various ethnic origins
      for mutations in the SUR1 gene. Single-strand conformation polymorphism (SSCP)
      and nucleotide sequence analyses of genomic DNA revealed a total of 17 novel and
      three previously described mutations in SUR1 . The novel mutations comprised one
      nonsense and 10 missense mutations, two deletions, three mutations in consensus
      splice-site sequences and an in-frame insertion of six nucleotides. One mutation
      occurred in the first nucleotide binding domain (NBF-1) of the SUR1 molecule and
      another eight mutations were located in the second nucleotide binding domain (NBF
      2), including two at highly conserved amino acid residues within the Walker A
      sequence motif. The majority of the remaining mutations was distributed
      throughout the three putative transmembrane domains of the SUR1 protein. With the
      exception of the 3993-9G-->A mutation, which was detected on 4.5% (4/88) disease
      chromosomes, allelic frequencies for the identified mutations varied between 1.1
      and 2.3% for HI chromosomes, indicating that each mutation was rare within the
      patient cohort. The clinical manifestations of HI in those patients homozygous
      for mutations in the SUR1 gene are described. In contrast with the allelic
      homogeneity of HI previously described in Ashkenazi Jewish patients, these
      findings suggest that a large degree of allelic heterogeneity at the SUR1 locus
      exists in non-Ashkenazi HI patients. These data have important implications for
      genetic counseling and prenatal diagnosis of HI, and also provide a basis to
      further elucidate the molecular mechanisms underlying the pathophysiology of this
      disease.

PMID- 9618170
TI  - Insertional mutation by transposable element, L1, in the DMD gene results in X
      linked dilated cardiomyopathy.
AB  - X-linked dilated cardiomyopathy (XLDCM) is a clinical phenotype of
      dystrophinopathy which is characterized by preferential myocardial involvement
      without any overt clinical signs of skeletal myopathy. To date, several mutations
      in the Duchenne muscular dystrophy gene, DMD , have been identified in patients
      with XLDCM, but a pathogenic correlation of these cardiospecific mutations in DMD
      with the XLDCM phenotype has remained to be elucidated. We report here the
      identification of a unique de novo L1 insertion in the muscle exon 1 in DMD in
      three XLDCM patients from two unrelated Japanese families. The insertion was a 5'
      truncated form of human L1 inversely integrated in the 5'-untranslated region in
      the muscle exon 1, which affected the transcription or the stability of the
      muscle form of dystrophin transcripts but not that of the brain or Purkinje cell
      form, probably due to its unique site of integration. We speculate that this
      insertion of an L1 sequence in DMD is responsible for some of the population of
      Japanese patients with XLDCM.

PMID- 9618171
TI  - De novo mutations (GAG deletion) in the DYT1 gene in two non-Jewish patients with
      early-onset dystonia.
AB  - The DYT1 gene recently has been cloned and shown to contain a three nucleotide
      (GAG) deletion responsible for most cases of autosomal dominant early-onset
      torsion dystonia. This deletion results in the loss of one of a pair of glutamic
      acids in a conserved region of a novel ATP-binding protein (torsinA). Previous
      haplotype analysis revealed that this same deletion had arisen at least two
      different times in history, suggesting independent mutational events. This
      deletion is the only sequence change found thus far to be associated uniquely
      with the disease status, regardless of ethnic origin. Here we describe two
      patients with typical early-onset torsion dystonia of Swiss-Mennonite and non
      Jewish Russian origin, respectively, that both carry this same mutation as a de
      novo GAG deletion. This finding proves that this 3 bp deletion in the DYT1 gene
      is indeed a mutation that causes early-onset torsion dystonia. The DYT1 mutation
      is one of the rare examples of the same recurrent mutation causing a dominantly
      inherited condition. The sequence surrounding the GAG deletion contains an
      imperfect 24 bp tandem repeat, suggesting a possible mechanism for the high
      frequency of this mutation.

PMID- 9618173
TI  - A mutation in human keratin K6b produces a phenocopy of the K17 disorder
      pachyonychia congenita type 2.
AB  - Type I and type II keratins form the heteropolymeric intermediate filament
      cytoskeleton, which is the main stress-bearing structure within epithelial cells.
      Pachyonychia congenita (PC) is a group of autosomal dominant disorders whose most
      prominent phenotype is hypertrophic nail dystrophy accompanied by other features
      of ectodermal dysplasia. It has been shown previously that mutations in either
      K16 or K6a, which form a keratin expression pair, produce the PC-1 variant (MIM
      184510). Mutations in K17 alone, an unpaired accessory keratin, result in the PC
      2 phenotype (MIM 184500). Here, we describe a family with PC-2 in which the K17
      locus on 17q was excluded and linkage to the type II keratin locus on 12q was
      obtained (Z max 3.31 at straight theta = 0). Mutation analysis of candidate
      keratins revealed the first reported missense mutation in K6b, implying that this
      keratin is the previously unknown expression partner of K17, analogous to the
      K6a/K16 pair. Co-expression of these genes was confirmed by in situ hybridization
      and immunohistochemical staining. These results reveal the hitherto unknown role
      of the K6b isoform in epithelial biology, as well as genetic heterogeneity in PC
      2.

PMID- 9618172
TI  - Reconstitution of wild-type or mutant telomerase activity in telomerase-negative
      immortal human cells.
AB  - Telomere shortening in human somatic cells and telomere maintenance in most human
      immortal cell lines and tumours correlate respectively with the absence and
      presence of telomerase, the enzyme that synthesizes telomeric DNA de novo .
      However, approximately 30% of in vitro immortalized human cell lines do not
      express this enzyme and maintain telomeres by an alternative pathway (ALT) that
      may also operate in some tumours. Human telomerase is a reverse transcriptase
      comprising minimally an RNA subunit (hTER) and a catalytic protein moiety
      (hTERT). Normal somatic cells retain expression of hTER but not of hTERT, and can
      be converted to a telomerase-positive phenotype by ectopic expression of the
      catalytic protein. We similarly have restored enzymatic activity to those ALT
      cell lines that retain hTER expression. We also report that in those ALT cells
      that are hTER negative, reintroduction of both hTER and hTERT is necessary and
      sufficient for conversion to telomerase positivity. Moreover, transfection of
      these cells with hTERT in conjunction with hTERs with a mutated template results
      in the expression of an enzyme with altered specificity. Reconstitution of
      telomerase activity in ALT cells, particularly an activity capable of
      synthesizing mutant telomeric DNA, may be exploited for the study of the ALT
      mechanism and its interaction with the telomerase-dependent pathway, and for
      assessing the effects of mutant telomeres on cell viability.

PMID- 9618174
TI  - Syntenic organization of the mouse distal chromosome 7 imprinting cluster and the
      Beckwith-Wiedemann syndrome region in chromosome 11p15.5.
AB  - In human and mouse, most imprinted genes are arranged in chromosomal clusters.
      Their linked organization suggests co-ordinated mechanisms controlling imprinting
      and gene expression. The identification of local and regional elements
      responsible for the epigenetic control of imprinted gene expression will be
      important in understanding the molecular basis of diseases associated with
      imprinting such as Beckwith-Wiedemann syndrome. We have established a complete
      contig of clones along the murine imprinting cluster on distal chromosome 7
      syntenic with the human imprinting region at 11p15.5 associated with Beckwith
      Wiedemann syndrome. The cluster comprises approximately 1 Mb of DNA, contains at
      least eight imprinted genes and is demarcated by the two maternally expressed
      genes Tssc3 (Ipl) and H19 which are directly flanked by the non-imprinted genes
      Nap1l4 (Nap2) and Rpl23l (L23mrp), respectively. We also localized Kcnq1 (Kvlqt1)
      and Cd81 (Tapa-1) between Cdkn1c (p57(Kip2)) and Mash2. The mouse Kcnq1 gene is
      maternally expressed in most fetal but biallelically transcribed in most neonatal
      tissues, suggesting relaxation of imprinting during development. Our findings
      indicate conserved control mechanisms between mouse and human, but also reveal
      some structural and functional differences. Our study opens the way for a
      systematic analysis of the cluster by genetic manipulation in the mouse which
      will lead to animal models of Beckwith-Wiedemann syndrome and childhood tumours.

PMID- 9618175
TI  - Human metalloprotease-disintegrin Kuzbanian regulates sympathoadrenal cell fate
      in development and neoplasia.
AB  - The development of the sympathetic nervous system involves cell-cell interactions
      that regulate the fate and migration of progenitor neural cells. Recent evidence
      shows that focal membrane-bound protease activity is critical for such
      interactions. The Drosophila kuzbanian (kuz) gene is required in neurogenesis and
      encodes a highly conserved, membrane-bound metalloprotease- disintegrin closley
      related to theTNF-alphaconvertingenzyme (TACE). We have characterized the human
      and mouse kuz homologs and mapped human kuz to chromosome 15q22. During mouse
      embryonic development Kuz is expressed mainly in the sympathoadrenal and
      olfactory neural precursors. Once sympathoadrenal cells differentiate into
      chromaffin cells in the adult adrenal medulla, they no longer express Kuz.
      However, we found that tumors of sympathoadrenal origin, such as
      pheochromocytomas and neuroblastomas, overexpress Kuz. Further, transfection of a
      kuz construct lacking the protease domain, but not the full-length construct,
      induces neurite formation in PC12 chromaffin tumor cells. Taken together our
      results suggest a critical role for Kuz in regulation of sympathoadrenal cell
      fate.

PMID- 9618176
TI  - NB4S, a member of the TBC1 domain family of genes, is truncated as a result of a
      constitutional t(1;10)(p22;q21) chromosome translocation in a patient with stage
      4S neuroblastoma.
AB  - Molecular cloning of the breakpoints of a t(1;10)(p22q21) constitutional
      translocation breakpoint in a patient with stage 4S neuroblastoma has identified
      two genes which are fused in-frame to generate a novel gene. The 1p22 gene, which
      we have called NB4S , encodes a 7.5 kb transcript with an 810 amino acid open
      reading frame and is expressed in a wide variety of tissues. NB4S has >88%
      homology with the mouse EVI -5 gene within the coding region and shows strong
      homology over a 200 amino acid region with TBC1 box motif genes involved in cell
      growth and differentiation. The C-teminal end of the protein contains a number of
      coiled coil domains, indicating a possible protein-protein binding function. The
      chromosome 10 breakpoint interrupts a novel transcript (TRNG10) which could only
      be detected in tumor cells. This transcript has no exon/intron structure or
      significant open reading frame, suggesting that it is a structural RNA which is
      transcribed but not translated. The chromosome rearrangement creates a fusion
      gene product which combines the TBC1 motif of NB4S with a polyadenylation signal
      from TRNG10 , potentially generating a truncated protein with oncogenic
      properties.

PMID- 9618177
TI  - Mutations in the retinal guanylate cyclase (RETGC-1) gene in dominant cone-rod
      dystrophy.
AB  - The dominant cone-rod dystrophy gene CORD6 has previously been mapped to within
      an 8 cM interval on chromosome 17p12-p13. The retinal-specific guanylate cyclase
      gene (RETGC-1), which maps to within this genetic interval and previously was
      implicated in Leber's congenital amaurosis, was screened for mutations within
      this family and in a panel of small families and individuals with various cone
      and cone- rod dystrophy phenotypes. A missense mutation (E837D) was identified in
      affected members of the CORD6 family, as well as a second missense mutation
      (R838C) in three other families with dominant cone-rod dystrophy. RETGC-1 is only
      the fourth gene to be implicated in cone-rod dystrophy and this is the first
      report of dominant mutations in this gene.

PMID- 9618178
TI  - Functional implications of the spectrum of mutations found in 234 cases with X
      linked juvenile retinoschisis. The Retinoschisis Consortium.
AB  - X-linked retinoschisis (XLRS) is the most common cause of juvenile macular
      degeneration in males, resulting in vision loss early in life. The gene involved
      in XLRS was identified recently. It encodes a protein with a disoidin domain,
      suggested to be involved in cell-cell interactions. We have screened the gene for
      mutations in 234 familial and sporadic retinoschisis cases and identified 82
      different mutations in 214 (91%). Thirty one mutations were found more than once,
      i.e. 2-10 times, with the exception of the 214G-->A mutation which was found in
      34 apparently unrelated cases. The origin of the patients, the linkage data and
      the site of the mutations (mainly CG dinucleotides) indicate that most recurrent
      mutations had independent origins and thus suggest the existence of a significant
      new mutation rate in XLRS1. The mutations identified cover the entire spectrum,
      from small intra-genic deletions (7%), to nonsense (6%), missense (75%), small
      frameshifting insertions/deletions (6%) and splice site mutations (6%). Since,
      regardless of the mutation type, no females with a typical RS phenotype were
      identified, RS seems to be caused by loss-of-function mutations only. Mutations
      occurred non-randomly, with hotspots at several CG dinucleotides and a C6stretch.
      Exons 1-3 contained few, mainly translation-truncating mutations, arguing against
      an important functional role for this segment of the protein. Exons 4-6, encoding
      the discoidin domain, contained most, mainly missense mutations. An alignment of
      32 discoidin domain proteins was constructed to reveal the consensus sequence and
      to deduce the functional importance of the missense mutations identified. The
      mutation analysis revealed a high preponderance of mutations involving or
      creating cysteine residues, pointing to sites important for the tertiary folding
      and/or protein function, and highlights several amino acids which may be involved
      in XLRS1-specific protein-protein interactions. Despite the enormous mutation
      heterogeneity, patients have relatively uniform clinical manifestations although
      with great intra-familial variation in age at onset and progression.

PMID- 9618179
TI  - Liposuction breast reduction.
AB  - All breast reductions since 1996 have been performed with only liposuction.
      Removal of up to 2250 ml per breast has been obtained in 45 patients, without any
      complications. Significant skin retraction results from a very superficial
      subcutaneous liposuction, with a significant volume reduction of the gland. One
      bilateral mastopexy was performed subsequently.

PMID- 9618180
TI  - Autologous fat injection for soft tissue augmentation in the face: a safe
      procedure?
AB  - Autologous fat injection for soft tissue augmentation in the face is claimed to
      be a safe procedure. However, there are several case reports in the literature
      where patients have suffered from acute visual loss and cerebral infarction
      following fat injections into the face. Acute visual loss after injection of
      various substances into the face is a well-known complication of such
      interventions. We report two further patients who suffered from ocular and
      cerebral embolism after fat injections into the face. For the intravasation of
      fat particles there are three preconditions: well-vascularized tissue,
      fragmentation of parenchyma, and, especially, a local increase in pressure in the
      affected tissue. Fat injections into the face lead to an acute local increase in
      pressure in highly vascularized tissue. We assume that fragments of fatty tissue
      reach ocular and cerebral arteries by reversed flow through branches of the
      carotid arteries after they are introduced into facial vessels. The manifestation
      of fat embolism appears either immediately after the fat injection or after a
      latency period. Fat embolism can remain subclinical and may not be recognized, or
      the clinical features may be misinterpreted. To minimize the risk of such a major
      complication, fat injections should be performed slowly, with the lowest possible
      force. One should avoid fat injections into pretraumatized soft tissue, for
      example, after rhytidectomy, because the risk of intravasation of fat particles
      may be higher. Metabolic disturbances such as hyperlipidemia may also contribute
      to the clinical manifestation of fat embolism Routine funduscopic examinations
      after fat injections into the face could help to provide data for future
      estimation of the patient's general risk.

PMID- 9618181
TI  - Blood loss and hematological recovery following reduction mammaplasty and
      dermolipectomy: a prospective study.
AB  - A study was made to assess the impact of surgery on the hematological status and
      postoperative hematological recovery of 75 consecutive patients undergoing either
      reduction mammaplasty or dermolipectomy. Blood losses were estimated the morning
      after surgery, measuring decreases in hemoglobin level and hematocrit, while
      postoperative recovery was evaluated in terms of hemoglobin level and hematocrit
      at 10 weeks. The postoperative hemoglobin decrease was 2.69 g%, and the
      hematocrit dropped 7.25%. By 10 weeks, however, the patients had recovered their
      preoperative values. We found no significant differences in the evolution of
      hemoglobin level and hematocrit during the study between reduction mammaplasty
      and dermolipectomy patients. A significant positive correlation between surgical
      piece weight and postoperative reduction in hemoglobin concentration and
      hematocrit was observed. Conversely, at 10 weeks, a significant but negative
      correlation between surgical specimen weight and hemoglobin concentration and
      hematocrit was recorded. The anticipated weight of the surgical piece could thus
      be used as a predictor of intraoperative blood loss and of the speed of
      postoperative recovery. Since patients with surgical resection of > 3 kg remained
      anemic at 10 weeks, oral iron supplements could benefit this subset of patients.

PMID- 9618182
TI  - Laser resurfacing of the neck: a review of 48 cases.
AB  - With the advent of the new sophisticated carbondioxide (CO2) laser, effective
      treatment of facial rhytides and pigmented lesions of the photodamaged skin has
      been gaining popularity. Partial and full facial skin resurfacings have been
      reported. However, resurfacing of the neck has been ignored or discouraged. The
      objective of this study is to assess the feasibility, benefits, and risks of
      laser resurfacing of the neck, combined with the additional resurfacing of the
      whole face. A total of 48 patients underwent the procedure with a high-power and
      short-exposure time CO2 laser (ultrapulse). Patients were evaluated and
      classified preoperatively. The great majority of patients had local anesthesia
      (topical and infiltrative) with minimal sedation. A computer pattern generator
      was used in all cases but one. In this paper, preoperative preparation,
      postoperative care, laser resurfacing techniques, and depth guidelines are
      discussed. Incorporating the neck with the facial resurfacing has given very
      satisfactory results, with minimal drawbacks.

PMID- 9618183
TI  - Toxic shock syndrome in plastic surgery patients: case report and review of the
      literature.
AB  - Toxic shock syndrome (TSS) is a rapidly developing disease, which may be lethal
      if not recognized and treated early. TSS unrelated to menstruation comprises an
      increasing proportion of the cases reported to the Centers for Disease Control
      during recent years, and a review of the literature reveals that TSS has is
      reported with increasing frequency in plastic surgical patients as well. The
      majority of reports relates to aesthetic plastic surgical procedures such as
      rhinoplasty, augmentation mammaplasty liposuction, and chemical peeling, but
      cases of TSS following reconstructive breast surgery with musculocutaneous flaps
      have also been reported. A common denominator seems to be that TSS occurs
      unexpectedly in healthy patients. Nonmenstrual TSS is apparently associated with
      a higher mortality rate than TSS associated with menstruation. We report on a
      case of TSS after exchange of silicone implants and resection of a siliconoma in
      a 59-year-old woman. Details of the case and a review of the literature are
      presented.

PMID- 9618184
TI  - Some ideas on relapse after remodeling of prognathism: aesthetic and functional
      results.
AB  - The efficiency of a surgical treatment is evaluated, mainly, by the stability of
      the results achieved, whether they are functional, aesthetic, or psychological.
      Relapse is the greatest problem in prognathism surgery. Among the probable causes
      of relapse, muscular actions are the main one. The author emphasizes the value of
      complete preoperative preparation, which includes clinical, cephalometric,
      occlusal, and functional analysis, and presents his surgical program: complete
      detachment of the periosteum of the ramus on the muscular area (the
      pterygomasseteric belt), a different surgical technique, L sagittal subcondylian
      osteotomy, and a maxillomandibular fixation (MMF) of just 6 to 10 days. He
      compares the results: relapses fall from a mean of 20% or more to a mere 2.4%,
      recovery of almost-normal function is achieved after about 1 month, and the
      treatment is more safe and comfortable for the patient.

PMID- 9618185
TI  - Endoscopic-assisted correction of the deviated nose.
AB  - The approach to nasal bone classic corrective rhinoplasty is an almost-blind
      technique, where the results depends on feeling by the surgeon's hand. To
      overcome these drawbacks, endoscopic-assisted corrective rhinoplasty and
      septoplasty were performed for 16 cases of deviated noses between January 1995
      and May 1997. The average follow-up period was 18 months. All patients were
      evaluated by symmetrical nasal pyramid, recurrence of the bony deflection, and
      septal deviation. The postoperative courses were satisfactory in most cases, with
      few complications. Compared with 28 cases of classic rhinoplasty, the patient
      satisfaction rate was high (87.5% in endoscopic-assisted rhinoplasty, 71.4% in
      classic rhinoplasty), and the complication and revision rate was low (0% in
      endoscopic-assisted rhinoplasty, 14.3 and 7.1% in classic rhinoplasty). But extra
      time (about 40 min) and greater expense were required for endoscopic-assisted
      rhinoplasty. It appeared to us that endoscopic control during corrective
      rhinoplasty and septoplasty is a big step toward obtaining better results in bony
      and cartilage resection with extreme precision under monitor control and
      magnification. This technique is not an open approach but permits one to see more
      of the nasal skeleton and bony septum, the cause of the deformity, and the
      immediate effect of the corrective measures used. The use of an endoscope in
      corrective rhinoplasty for deviated noses provides an expanded field of vision,
      direct manipulation of lesions, and better aesthetic and functional results.

PMID- 9618186
TI  - Augmentative rhinoplasty with an "auricular gibbus".
AB  - The philosophy of this work is to revise an interesting way to compensate a lack
      of nasal volume. Autologous auricular cartilage is used to augment a hollow
      dorsum. In this way, we treat depressed, asymmetrical, and irregular dorsa. We
      have 10 years' experience with this technique, in a total of nearly 350 cases.
      Among these cases are traumatic, secondary, and congenital noses. Prior to using
      this technique, we employed nasal septum, iliac crest bone or calotte, rib,
      dermis, fascia, etc. But actually, the "neogibbus" provided by the upper fossette
      of the concha of the auricle is enough, except for cases of exceptional volume
      needs. The ear does not suffer any damage when it is treated appropriately, and a
      uni- or bilateral graft can be taken, if necessary, to create a strong gibbus in
      the manner of a "sarcophagus" or of "Russian dolls."

PMID- 9618187
TI  - Deviated nose: technical proposition for prevention of recurrences.
AB  - After considering previously published studies and accordant with their
      observations during operations, the authors propose a surgical technique for the
      treatment of the deviated nose. Subpericondrial liberation of the upper lateral
      cartilages on the concave surface, with regard to the deviation, helps to prevent
      recurrences. After illustration of the surgical technique, some representative
      clinical cases are presented.

PMID- 9618188
TI  - Use of porous high-density polyethylene in revision rhinoplasty and in the
      platyrrhine nose.
AB  - Nasal reconstruction presents a significant challenge to the facial plastic
      surgeon. Reestablishment of the desired aesthetic nasal contour and restoration
      of respiratory function are the dual goals of this endeavor. While autologous
      cartilage or bone is considered optimal grafting material, the supply is often
      limited and harvesting entails additional morbidity. Many synthetic materials
      have been introduced for use in nasal reconstruction, but high infection and
      extrusion rates have left most surgeons dissatisfied with conventional implants.
      Porous polyethylene (Medpor) implants were used for nasal reconstruction in 187
      patients; 66 (35.3%) patients underwent primary rhinoplasty, while revision
      surgery was performed in 121 (64.7%) patients. Most patients required multiple
      implants, including columella struts, plumper grafts, dorsal tip implants, and
      nasal valve battens. Postoperative follow-up ranged from 6 months to 3.5 years.
      Complications occurred in five (2.6%) patients. Three early and two delayed
      infections necessitated implant removal in five patients, all of whom had
      compromised skin-soft tissue envelopes secondary to heavy smoking, cocaine abuse,
      or prior surgery. One case of an overly augmented nasal dorsum and tip required
      implant removal, reduction, and reinsertion. All implants were easily removed. No
      other complications including implant extrusion or skin erosion have been noted.
      Porous polyethylene (Medpor) implants allow for fibrovascular ingrowth, which
      lends stability to the implant. Porous polyethylene implants are well tolerated
      and provide an ideal material for nasal reconstruction.

PMID- 9618189
TI  - Late Klebsiella pneumoniae infection following breast augmentation: case report.
AB  - A case is reported of late infection in a breast implant, in a 35-year-old female
      who underwent breast augmentation with a double-lumen silicone prosthesis
      combined with abdominoplasty. After 8 uneventful postoperative months, untoward
      and poorly defined symptoms occurred and further exploratory surgery became
      necessary. Due to a subacute inflammatory process in the entire pocket of the
      left breast, the implants were removed. Culture demonstrated Klebsiella
      pneumoniae. After complete healing, a pair of texturized moderate profile
      implants was placed above the muscle through an areolar access. The clinical
      history and management of this unusual case are described.

PMID- 9618190
TI  - The waist and abdominoplasty.
AB  - Basing our work on ideal aesthetic features of the feminine figure and focusing
      our attention on the waist, we add several points to the abdominoplasty
      classification. We have carried out 150 abdomino plasties in the last 5 years:
      60% of the patients presented with musculoponeurosis alterations, for whom
      plicature of the rectus abdominis and obliques with wide dissection was
      accomplished, and 40% with mainly fat excess at the flanks, on whom limited
      dissection and liposuction were performed. Our objective was to achieve an ideal
      waist for each patient.

PMID- 9618191
TI  - Partial myotomy of the pectoralis major in submuscular breast implants.
AB  - Several authors report that retropectoral or submuscular placing for prostheses
      reduces the incidence of capsular contracture, preserves the sensitivity of the
      areola, and gives the breast a more natural look; however, displacement of the
      prosthesis when contracting the arm, shoulders, and thorax muscles is often
      observed. In order to prevent this deficiency, partial thickness myotomy was
      performed in the pectoralis major muscle. Since 1987, our team has carried out
      120 subpectoral augmentation mammoplasties by submammary approaches using this
      procedure. The ages of the patients ranged from 19 to 44 years old. In all cases,
      physiological saline microtextured prostheses were used. Volumes were between 225
      and 275 cc. The results were satisfactory in all cases, with no hematomas,
      infections or capsular contractures. The main advantage of this technique is that
      it prevents displacement of the prostheses after movements of the arms or
      shoulders.

PMID- 9618193
TI  - An electrochemical enzyme immunoassay for chicken luteinizing hormone: extension
      of the detection limit by adequate control of the nonspecific adsorption.
AB  - A noncompetitive heterogeneous enzyme immunoassay for the determination of
      chicken luteinizing hormone (LH) was equipped with an electrochemical endpoint in
      order to further enhance its sensitivity. The immunological principle of the
      original ELISA remained essentially unchanged, except for the fact that the
      peroxidase label was replaced by alkaline phosphatase, since in the upgraded
      version of the assay, p-aminophenyl phosphate was to be used as the substrate of
      alkaline phosphatase. Enzyme-generated p-aminophenol was injected into a flow
      injection system and detected amperometrically in a thin-layer flow cell with a
      glassy carbon electrode at 0.325 V vs Ag/AgCl. A classical problem associated
      with this type of solid-phase immunoassay is the adsorption of proteins other
      than the capture antibody to the solid phase. The detection sensitivity is
      therefore often limited by a large background signal observed in the absence of
      antigen. In the present study, an experiment was designed to examine in each step
      of the assay the contribution of each of the potential sources of background
      current. It was shown that the major contribution to the background current was
      caused by the nonspecific adsorption of biotinylated secondary antibody.
      Adsorption of the secondary antibody (biotinylated goat anti-rabbit IgG) to the
      capture antibody (mouse anti-chicken LHbeta) was clearly a case of specific
      aspecificity, whereas adsorption to the solid phase itself had to be treated as a
      nonspecific aspecificity. Addition of 0.25% mouse serum to the secondary antibody
      as a source of mouse immunoglobulin could overcome the cross-reaction and
      markedly reduced adsorption to capture antibody. The second part of nonspecific
      adsorption was eliminated by using combinations of Tween 20 and bovine serum
      albumin as blocking agents. Controlling the adsorption of the biotinylated
      secondary antibody in this way decreased the detection limit from 39 pg/ml in the
      original assay to 2.5 pg/ml in the electrochemical version. This way, the plasma
      volume of samples containing on the order of 1 ng/ml LH was reduced to less than
      10 microl. The linear range was 2.5-625 pg/ml. The method allowed us to measure
      LH in buffer and in adult and juvenile chicken plasma.

PMID- 9618194
TI  - Automated analysis of mitochondrial enzymes in cultured skin fibroblasts.
AB  - We report automated methods for assaying the activities of the mitochondrial
      respiratory chain enzyme cytochrome c oxidase (COX), the matrix enzyme citrate
      synthase (CS), and the cytoplasmic enzyme lactate dehydrogenase (LDH) on a random
      access analyzer, the Roche Mira S. COX activity was assayed by measuring the
      initial rate of oxidation of reduced cytochrome c. The CS assay was based on the
      reaction of this enzyme with oxaloacetate and acetyl-CoA to produce CoASH, which
      further reacts with dithionitrobenzoic acid producing a free thionitrobenzoate
      ion. LDH activity was assayed by measuring the reduction of nicotinamide adenine
      dinucleotide during the oxidation of lactate to pyruvate. Precision of the COX
      assay was 2. 3%, CS assay 0.7%, and LDH 5.6%. These automated methods were faster
      by as much as 80%, cheaper by 50%, and used less than half the sample material
      needed for traditional manual methods. While these assays are often performed by
      specialized laboratories using dedicated staff, the automated methods presented
      here are easily performed by staff trained in the regular diagnostic laboratory.

PMID- 9618195
TI  - Infrared spectroscopic analysis of biomedical specimens using glass substrates.
AB  - We report on the use of glass substrates for the infrared spectroscopic analysis
      of dried serum, amniotic fluid, and synovial fluid films. New analytical
      applications of infrared spectroscopy are emerging rapidly, spurred largely by
      ever-improving instrumentation, combined with the widespread availability of
      powerful chemometric methods. We have recently begun to focus upon potential
      applications in both clinical chemistry and medical diagnostics. For example,
      serum analysis, the determination of fetal lung maturity, and the differential
      diagnosis of arthritis have all recently been demonstrated to be feasible on the
      basis of the infrared spectra of films dried from the appropriate samples (serum,
      amniotic fluid, or synovial fluid). However, the transition from the laboratory
      into clinical usage hinges on the availability of IR-transparent substrates that
      are both inexpensive and readily obtainable. We have demonstrated in this study
      that despite limited transparency in the IR region, clinical analyses and
      diagnostic spectral classifications may nevertheless be carried out using glass
      as a substrate for the IR measurements.

PMID- 9618196
TI  - A single plasmid vector (pSTAR) mediating efficient tetracycline-induced gene
      expression.
AB  - A plasmid vector (pSTAR) has been constructed which confers neomycin resistance
      for selecting stably transfected cells, possesses a cloning cassette for placing
      a gene of interest under the control of the tetO DNA motif, and expresses rtTAnls
      which, upon association with tetracycline, binds to and drives gene expression
      from the tetO DNA motif. The plasmid pSTAR/LacZ, which has the gene for beta
      galactosidase inserted into the cloning cassette, was transfected into Chinese
      hamster ovary (CHO) cells and selected for stably transfected cells. In pooled
      transfectants of CHO, tetracycline induced the expression of beta-galactosidase
      in 10-30% of cells. Using clonal transfectants, beta-galactosidase expression was
      induced by tetracycline in essentially every cell. Furthermore, induction of beta
      galactosidase expression by tetracycline was both dose- and time-dependent.
      Similar tetracycline-induced beta-galactosidase expression is also observed in
      other cell types. The pSTAR vector is thus suited to facilitate the application
      of tetracycline-induced gene expression in diverse research areas.

PMID- 9618197
TI  - Analysis of a 3.6-MDa hexagonal bilayer hemoglobin from Lumbricus terrestris
      using a gas-phase electrophoretic mobility molecular analyzer.
AB  - The recent successful use of electrospray gas-phase electrophoretic mobility
      molecular analysis (GEMMA) to separate globular proteins (mass 6 to 670 kDa) and
      the excellent correlation found between the electrophoretic mobility diameter
      (EMD), or Millikan diameter, and the protein mass (S. L. Kaufman et al., 1996,
      Anal. Chem. 68, 1895-1904; 1996, Anal. Chem. 68, 3703), prompted the examination
      of a large protein complex, the 3.6-MDa, heteromultimeric, hexagonal bilayer
      hemoglobin (Hb) and its subunits from the earthworm Lumbricus terrestris. The
      native Hb had an EMD of 25.7 nm and the products of its dissociation at pH >8 and
      <5 were resolved into peaks with EMDs of 10.5, 6.3, 5.0, and 4.2 nm, identified
      as a dodecamer of globin chains ([a+b+c]3d3, 213 kDa), the disulfide-bonded
      trimer of globin chains ([a+b+c], 52.7 kDa), all the linker chains (L1, 27.5 kDa;
      L2, 32.1 kDa; L3, 24.9 kDa; L4, 24. 1 kDa), and the monomer subunit (chain d, 17
      kDa), respectively. Reassembly of the Hb complex was observed on restoring the pH
      from >8 to 7. The EMDs and the masses of the Hb and its subunits are in excellent
      agreement with the correlation found earlier, under the assumption of nearly
      spherical shape with an effective density around 0.7 g/cm3. GEMMA also provided a
      profile of the Hb completely dissociated in 0.1% SDS; its deconvolution permitted
      a quantitative determination of the subunit stoichiometry, providing a globin to
      linker ratio of 3 to 1.

PMID- 9618198
TI  - Simultaneous analysis of amino and organic acids in extracts of plant leaves as
      tert-butyldimethylsilyl derivatives by capillary gas chromatography.
AB  - The simultaneous determination of amino and organic acids in plant tissue
      extracts using capillary gas chromatography is described. Plant leaves were
      extracted in 5% (w/v) perchloric acid and neutralized extracts were purified
      using C18 cartridges. The amino and organic acids in purified extracts were then
      converted to tert-butyldimethylsilyl (TBDMS) derivatives prior to separation and
      detection by capillary gas chromatography (GC) with flame ionization detection.
      Conditions required for optimal derivatization were investigated. Amino and
      organic acids were readily converted to their TBDMS derivatives using N-methyl-N
      tert-butyldimethylsilyltrifluoroacetamide in dimethylformamide solvent 1:6 (v/v)
      with an average recovery of 90% and a reproducibility of about 5%. The
      characteristic [M-57] and [M-159] fragment ion of the TBDMS derivatives was
      confirmed using GC-MS. The proposed method was demonstrated by the determination
      of amino and organic acids in extracts of Acacia and Eucalyptus leaves, where
      detection limits were 1-20 ng.

PMID- 9618199
TI  - Detection of membrane-bound enzymes in cells using immunoassay and Raman
      microspectroscopy.
AB  - The method of surface-enhanced Raman microspectroscopy was developed for direct
      detection of membrane-bound enzymes in cells. Cells were cultured, fixed, and
      incubated with specific primary antibodies and their corresponding labeled
      secondary antibodies, and surface-enhanced Raman scattering (SERS) was detected
      directly in the wells of a multiwell plate. First, specific primary antibodies
      were separately bound to enzymes in cells. Then, the peroxidase-labeled secondary
      antibodies were added to bind these primary antibodies. Peroxidase substrates, o
      phenylenediamine and hydrogen peroxide, were added and reacted for 15 min at room
      temperature to form azoaniline, a compound with strong Raman scattering. Then,
      Raman scattering of this enzymatic product was enhanced by silver colloids.
      Samples were excited with a He/Ne laser at 632.8 nm and SERS was detected by a
      CCD camera. The SERS spectrum of this product showed an intense peak at 1370 cm-1
      and its intensity was used for assessment of cellular enzymes. The observed
      amount of enzyme was normalized to protein content in each well. The method was
      successfully used to detect prostaglandin H synthase-1 and -2 (PGHS-1 and -2) in
      normal human hepatocytes and human hepatocellular carcinoma (HepG2) cells. The
      detection limit of these PGHS enzymes by this method was about 0.1 pg per well.
      An immunohistochemical staining was also used to detect the expression of both
      PGHS isozymes in these cells.

PMID- 9618200
TI  - Stabilization of proteins and peptides in diagnostic immunological assays by the
      molecular chaperone Hsp25.
AB  - Diagnostic assays for proteins devoid of enzymatic activity are becoming
      increasingly important. Antibodies generated against the respective proteins are
      used for their detection in enzyme-linked immunosorbent assay or patient sera are
      used to monitor disease-related antibodies against recombinantly produced
      antigens. A problem frequently encountered with these assays is that the proteins
      or fragments thereof used as standards have a limited shelf life. A similar
      problem arises when activities of labile enzymes are used for diagnostic
      detection. Here, we present a novel approach to 'stabilizing' enzymatic activity
      and antigenicity of proteins used for immunogenic detection by molecular
      chaperones. We have exploited the ability of molecular chaperones to keep
      proteins in their active conformation to overcome the biotechnological problems
      encountered in protein-based diagnostics of heart attack, stroke, and viral
      infections such as hepatitis C. We show that Hsp25, a member of the family of
      small heat shock proteins, known to act as a molecular chaperone in protein
      folding reactions, can stably bind labile standard proteins. Complex formation
      does not interfere with immunogenic detection and, importantly, antigenic as well
      as enzymatic activity remains constant for weeks. This strategy seems to be
      applicable to a wide range of assays involving unstable proteins, including the
      generation of vaccines.

PMID- 9618201
TI  - Quantitative reverse transcription strand displacement amplification:
      quantitation of nucleic acids using an isothermal amplification technique.
AB  - Recent advances in nucleic acid amplification techniques have allowed for
      quantitation of viral nucleic acid levels in clinical specimens. The most
      prevalent testing is carried out for HIV viral load. Strand displacement
      amplification (SDA) is an isothermal DNA amplification system utilizing a
      restriction enzyme and a DNA polymerase with strand displacement properties. SDA
      was adapted for quantitative RNA amplification (QRT-SDA) of an HIV gag sequence
      by including AMV reverse transcriptase, a quantitative control sequence, and 32P
      labeled detector oligonucleotides for the HIV and the control sequences. We have
      also improved the amplification efficiency by including the single-strand binding
      protein from gene 32 of T4 bacteriophage (T4gp32) to enhance strand displacement
      replication. In a preliminary analytical demonstration of the technique, RT-SDA
      was quantitative to within twofold over a range of 500-500,000 transcripts that
      were generated from a plasmid bearing an HIV gag sequence. QRT-SDA potentially
      represents a convenient alternative for viral load testing in a clinical setting.

PMID- 9618202
TI  - Identification and cloning of differentially expressed genes by long-distance
      differential display.
AB  - Differential mRNA display (DD-PCR) amplifies short cDNAs (average size 100-350
      bp), representing mainly the 3' untranslated regions (3' UTR) of transcripts.
      Sequencing of these cDNAs is predominantly uninformative for prediction of
      function and selection of clones for further analysis. Differential display of
      longer amplicons (0.5-2.0 kb) could enable isolation of cDNAs that encompass both
      3' UTR and at least part of the 3' end of the coding region. The coding sequence
      information could facilitate selection of candidate clones for further analysis
      without the necessity of screening cDNA libraries. By combining DD-PCR protocols
      with long-distance PCR and using hot-start PCR with rTth DNA polymerase we have
      successfully amplified and comparatively displayed cDNAs ranging in size from 150
      bp to 2 kb. Long-distance DD-PCR (LDD-PCR) has generated highly reproducible
      primer-specific patterns of cDNA fragments, as well as reproducible duplicate
      fingerprints, obtained from different RNA and cDNA samples. Sequencing and
      expression analyses of LDD-PCR clones have shown that LDD-PCR (a) enables
      nonredundant clone sampling, (b) generates many clones that encompass part of the
      coding region, and (c) samples both abundant and rare transcripts, approximately
      60% of which are differentially expressed as confirmed by Northern analysis.
      Coupled with high-throughput cDNA sequencing and multiplex hybridization of cDNA
      microarrays for confirmation of differential expression, LDD-PCR could prove to
      be useful for simultaneous scanning of transcripts from multiple cDNA samples and
      faster selection of differentially expressed transcripts of interest.

PMID- 9618203
TI  - Sample preparation and high-performance liquid chromatographic analysis of
      deoxyribonucleoside triphosphates in individual rat embryos.
AB  - A rapid, robust, and sensitive method has been developed to measure
      concentrations of deoxyribonucleoside triphosphates in individual, day 14 rat
      embryos by modifying and optimizing existing methods for cellular extracts.
      Significant changes include: (i) oxidative degradation of ribonucleoside
      triphosphates using methylamine at lower pH (decreased from 6.5 to 4.0) to
      improve poor HPLC peak shape of early eluting nucleotides; (ii) glass fiber disc
      solid-phase extraction of the reaction mixture, which dramatically reduces
      impurities that interfere with nucleotide measurement, eliminates the necessity
      of column regeneration, and allows mobile phase recycling; and (iii) lower ionic
      strength (reduced from 0.4 to 0.26 or 0.12 M ammonium phosphate) and higher pH
      (increased from 3.25 to 5.55 or 6.98, respectively) mobile phase, conditions
      which are less destructive to the column's bonded phase and silica support,
      thereby contributing to longer column life. Enhancements include: (i) filtration
      of the sample prior to HPLC injection and addition of an in-line filter, guard
      column, and saturating precolumn of silica in the mobile phase flow, which aids
      substantially in extending column life and improves chromatographic stability,
      and (ii) inclusion of an internal standard to correct for mechanical losses.
      Limits of determination at a signal to noise ratio of 6:1 range from 5.5 to 12
      pmol on-column or 0.41 to 0.87 pmol/mg of embryonic tissue depending on the
      specific nucleotide. Recoveries are quantitative for all nucleotides, and
      interassay variabilities are between 5 and 7% when quantified by peak height. The
      method has also been applied successfully to analysis of murine erythroleukemic
      cell cultures and this, when coupled with the embryo results, suggests its
      general utility.

PMID- 9618204
TI  - Simultaneous extraction and derivatization of carbohydrates from green plant
      tissues for analysis by gas-liquid chromatography.
AB  - Simultaneous extraction and derivatization of carbohydrates was performed by
      mixing dry ground plant tissue with derivatization reagents in pyridine;
      trimethylsilyl derivatives were analyzed by gas-liquid chromatography. This
      "direct analysis" was compared to analysis of samples prepared by exhaustive
      ethanol extraction of the same ground plant tissues. Comparisons included leaf
      blades from apple, grape, corn, and tomato and leaf blade, petiole, stem, and pod
      tissues from soybean plants. Direct analysis gave superior quantification of
      sucrose, glucose, and fructose because of sucrose hydrolysis during ethanol
      extraction. Sucrose hydrolysis was highly variable among plant species and use of
      hot ethanol at the first extraction step reduced sucrose hydrolysis but did not
      always abolish it. Sucrose hydrolysis was probably due to the activity of
      hydrolytic enzymes in 75% ethanol at room temperature. Direct analysis was
      inferior for the quantification of cyclitols in the fibrous tissues of soybean
      but provided acceptable results for cyclitol analysis in leaf blade tissue. When
      the time for extraction/reaction was extended from 40 to 60 min, some improvement
      in recovery of cyclitols was observed, but recovery remained 10 to 20% below that
      obtained with exhaustive ethanol extraction. Mannitol was vacuum infiltrated into
      the five types of leaf tissue and recovery averaged 100% by the direct method
      relative to ETOH extraction for apple, grape, corn, and soybean leaves but was
      only 76% for tomato leaves. Direct analysis provides very large time savings and
      is clearly the method of choice when the analysis of large numbers of samples of
      plant tissues for carbohydrate composition is required.

PMID- 9618205
TI  - A sandwich hybridization assay employing enzyme amplification for termination of
      specific ribosomal RNA from unpurified cell lysates.
AB  - We have employed the power of the cyclic NAD-based enzyme amplification system to
      the determination of 16S rRNA. This generally applicable system employs two
      oligonucleotide probes, one of which is captured on a microtiter well surface and
      the other labeled with alkaline phosphatase. The detection of very low levels of
      hybridization of the capture probe is then achieved by the means of the
      ultrasensitive enzyme-amplified assay system, resulting in a highly sensitive,
      convenient, and rapid technology which can be directly employed on unpurified
      samples. We have been able to demonstrate the detection of 20 amol (10(7)
      molecules) of pure rRNA, and specific signals from as few as 2000 bacterial cells
      have also been demonstrated. The total procedural time can be short-5 to 18 h
      depending on the dynamic range and sensitivity required. RNA target in the range
      of 10(12)-10(8) molecules can be assayed within 5 h. Extending the substrate
      incubation time enables between 10(11) and 10(7) molecules to be determined
      within 18 h. The system has great potential use with respect to studying the
      distribution and physiological states of cellular organisms.

PMID- 9618206
TI  - A continuous spectrophotometric method based on enzymatic cycling for determining
      L-glutamate.
AB  - A continuous spectrophotometric assay for determining low levels of L-glutamate
      is described. The assay, which involves the enzymes L-glutamate oxidase and
      glutamic-pyruvic transaminase, is based on the recycling of L-glutamate into
      alpha-ketoglutarate, with the concomitant appearance of one molecule of hydrogen
      peroxide in each turn of the cycle. This is subsequently reduced by means of a
      peroxidase-coupled reaction, using 2, 2'-azinobis(3-ethylbenzthiazoline-6
      sulfonic acid) as substrate. In this way the interference observed in the cyclic
      assay using glutamic-oxalacetic transaminase, which is due to the fact that L
      aspartate is also a substrate of L-glutamate oxidase, is eliminated. A kinetic
      study of the system is presented, with the accumulation of chromophore being seen
      to undergo a transient phase, which is dependent both on the cycling rate and on
      the auxiliary enzyme concentration. The kinetic parameters characterizing the
      system have been determined, making it possible to optimize costs with respect to
      the enzymes involved in the cycle, since the minimum amount needed for a given
      rate constant of the cycle can be calculated.

PMID- 9618207
TI  - A DNA assay based on fluorescence resonance energy transfer and DNA triplex
      formation.

PMID- 9618208
TI  - A direct microfluorometric method for measuring subpicomole amounts of
      nicotinamide adenine dinucleotide phosphate, glucose, and glycogen.

PMID- 9618209
TI  - Improved reproducibility in the monosaccharide composition analysis of
      immunoglobulin G using the CarboPac PA-100 column.

PMID- 9618210
TI  - Immunodot blot method for the detection of poly(ADP-ribose) synthesized in vitro
      and in vivo.

PMID- 9618211
TI  - A polymerase chain reaction inhibitor of ancient hard and soft tissue DNA
      extracts is determined as human collagen type I.

PMID- 9618212
TI  - Recovery of Tn5-flanking bacterial DNA by vector-mediated walking from the
      transposon to the host genome.

PMID- 9618213
TI  - A DNA glycosylase-based fingerprint for accurate identification of amplified DNA
      products and its application in the accurate diagnosis of infectious organisms.

PMID- 9618214
TI  - Cadherin-Defined Segments and Parasagittal Cell Ribbons in the Developing Chicken
      Cerebellum.
AB  - In the developing chicken cerebellar cortex, three cadherins (Cad6B, Cad7, and R
      cadherin) are expressed in distinct parasagittal segments that are separated from
      each other by ribbons of migrating interneurons and granule cells which express R
      cadherin and Cad7, respectively. The segment/ribbon pattern is respected by the
      expression of other types of molecules, such as engrailed-2 and SC1/BEN/DM-GRASP.
      The cadherin-defined segments contain young Purkinje cells which are connected to
      underlying nuclear zones expressing the same cadherin, thereby forming
      parasagittal cortico-nuclear zones of topographically organized connections. In
      addition, R-cadherin-positive mossy fiber terminals display a periodic pattern in
      the internal granular layer. In this layer, Cad7 and R-cadherin are associated
      with synaptic complexes. These results suggest that cadherins play a pivotal role
      in the formation of functional cerebellar architecture by providing a three
      dimensional scaffold of adhesive information. Copyright 1998 Academic Press.

PMID- 9618215
TI  - Utrophin mRNA Expression in Muscle Is Not Restricted to the Neuromuscular
      Junction.
AB  - Utrophin is normally present exclusively in synaptic regions of skeletal muscle
      fibers, although it is expressed extrasynaptically in certain pathological
      situations, where it has been proposed to compensate for the absence of
      dystrophin in Duchenne muscular dystrophy patients and mdx mice. Recently there
      have been conflicting reports regarding the preferential expression of utrophin
      mRNA at the neuromuscular junction. Using in situ hybridization with RNA probes,
      we show a clear accumulation of autoradiographic labeling at more than 90% of
      neuromuscular junctions (identified by histochemical demonstration of
      cholinesterase activity). The intensity of this labeling is proportional to the
      number of junctional myonuclei in the section. Some clusters of labeling were
      found associated with nonmuscle nuclei (e.g., blood vessels, nerves), where
      utrophin is present. In addition, labeling for utrophin mRNA was associated with
      about 25% of extrajunctional myonuclei, where the protein is not present. The
      mean labeling per nucleus at junctional myonuclei was at least 10 times greater
      than at extrajunctional myonuclei. We discuss the possible regulatory mechanisms
      involved in the heterogeneous expression of utrophin mRNA in skeletal muscle.
      Copyright 1998 Academic Press.

PMID- 9618216
TI  - Dystonin Is Essential for Maintaining Neuronal Cytoskeleton Organization.
AB  - The mouse neurological mutant dystonia musculorum (dt) suffers from a hereditary
      sensory neuropathy. We have previously described the cloning and characterization
      of the dt gene, which we named dystonin (Dst). We had shown that dystonin is a
      neural isoform of bullous pemphigoid antigen 1 (Bpag1) with an N-terminal actin
      binding domain. It has been shown previously that dystonin is a cytoskeletal
      linker protein, forming a bridge between F-actin and intermediate filaments.
      Here, we have used two different antibody preparations against dystonin and
      detected a high-molecular-weight protein in immunoblot analysis of spinal cord
      extracts. We also show that this high-molecular-weight protein was not detectable
      in the nervous system of all dt alleles tested. Immunohistochemical analysis
      revealed that dystonin was present in different compartments of neurons-cell
      bodies, dendrites, and axons, regions which are rich in the three elements of the
      cytoskeleton (F-actin, neurofilaments, and microtubules). Ultrastructural
      analysis of dt dorsal root axons revealed disorganization of the neurofilament
      network and surprisingly also of the microtubule network. In this context it is
      of interest that we observed altered levels of the microtubule-associated
      proteins MAP2 and tau in spinal cord neurons of different dt alleles. Finally, dt
      dorsal root ganglion neurons formed neurites in culture, but the cytoskeleton was
      disorganized within these neurites. Our results demonstrate that dystonin is
      essential for maintaining neuronal cytoskeleton integrity but is not required for
      establishing neuronal morphology. Copyright 1998 Academic Press.

PMID- 9618217
TI  - Organizing Effects of Rapsyn on Neuronal Nicotinic Acetylcholine Receptors.
AB  - Targeting receptors to appropriate locations on the cell surface is a critical
      task for neurons. We have examined the possibility that rapsyn controls the
      distribution of nicotinic receptors on neurons as it does nicotinic receptors on
      muscle fibers. Cotransfection of QT6 cells with rapsyn and neuronal nicotinic
      receptor cDNA constructs produced receptor aggregates or clusters that
      codistributed in part with rapsyn protein. Though all nicotinic receptor subtypes
      tested were affected by rapsyn, receptors containing the alpha7 gene product were
      among the most responsive. In addition, rapsyn caused a portion of the nicotinic
      receptors containing alpha7 subunits to become resistant to solubilization with
      nonionic detergent and to display a marked increase in metabolic stability. The
      results are consistent with rapsyn linking the receptors to cytoskeletal elements
      and suggest that it may play an organizing role determining the fate and location
      of nicotinic receptors on neurons. Copyright 1998 Academic Press.

PMID- 9618218
TI  - LAR Tyrosine Phosphatase Receptor: A Developmental Isoform Is Present in Neurites
      and Growth Cones and Its Expression Is Regional- and Cell-Specific.
AB  - Transgenic mice and Drosophila mutant studies demonstrate that the leukocyte
      common antigen-related (LAR) protein tyrosine phosphatase (PTPase) receptor is
      required for formation of neural networks. We assessed the hypothesis that
      alternative splicing of the LAR extracellular region contributes to this function
      by establishing temporospatial expression patterns of LAR isoforms containing an
      alternatively spliced extracellular nine amino acid segment (LAR alternatively
      spliced element-c; LASE-c). LASE-c was present in multiple alternatively spliced
      and truncated LAR transcripts. In contrast to LAR isoforms without LASE-c, levels
      of LAR transcripts and protein isoforms containing LASE-c were primarily present
      during development, suggesting a mechanism for developmental regulation of LAR
      function. In situ analysis demonstrated increasingly region- and cell-specific
      expression of LASE-c during maturation. Immunostaining revealed LASE-c-containing
      LAR protein along neurites and in growth cones. The discovery of highly
      regulated, temporospatial extracellular domain alternative splicing of LAR-type
      PTPase receptors points to a novel mechanism by which these receptors might
      influence network formation. Copyright 1998 Academic Press.

PMID- 9618219
TI  - Alternative Splicing of Human NrCAM in Neural and Nonneural Tissues.
AB  - Neural cell adhesion molecule NrCAM exists in a variety of isoforms as a result
      of alternative splicing of individual exons during RNA processing. In this report
      we demonstrate that many of the alternative splicing events described for chick
      are conserved in man and describe a novel variant of NrCAM cDNA. Furthermore, we
      show that NrCAM is expressed at significant levels outside the nervous system; in
      particular in pancreas, adrenal glands, and placenta and that expression in both
      brain and other tissues is accompanied by a very variable pattern of exon
      utilization in fetal and adult cells. Copyright 1998 Academic Press.

PMID- 9618220
TI  - Changes in Epidermal Growth Factor Receptor Expression and Competence to Generate
      Glia Regulate Timing and Choice of Differentiation in the Retina.
AB  - Previous studies demonstrated that the level of epidermal growth factor receptors
      (EGF-Rs) expressed by progenitor cells in the newborn (P0) rat retina was
      limiting for the generation of Muller glial cells but not for proliferation. To
      determine whether EGF-R signaling biases cells to generate a specific cell type
      or regulates more general processes during progenitor cell development, we have
      introduced extra copies of the EGF-R into progenitor cells at earlier stages (E15
      and E18), when different cell types are produced. We show that progenitor cells
      in early embryonic retina (E15) normally express lower levels of EGF-Rs than
      progenitor cells in later retina (E18 and P0). Whereas lower levels of
      stimulation of endogenous and virally transduced EGF-Rs enhanced proliferation,
      higher levels reduced proliferation, resulting in premature differentiation. At
      E15, very few EGF-R-infected progenitor cells differentiated prematurely into
      Muller glial cells, unlike E18 and P0 cells, even when they were exposed to an
      older retinal environment. Higher levels of EGF-R-mediated signaling alone
      therefore do not specify a glial fate, indicating that competence to generate
      glia is temporally regulated by additional mechanisms. The differences in EGF-R
      expression observed among retinal progenitor cells at distinct developmental
      stages may instead help to define signaling thresholds which delay or accelerate
      their differentiation. Copyright 1998 Academic Press.

PMID- 9618221
TI  - The Neuron-Glia Signal beta Neuregulin Induces Sustained CREB Phosphorylation on
      Ser-133 in Cultured Rat Schwann Cells.
AB  - beta neuregulins (also called NDF, GGF, ARIA, and heregulins) are neuron-derived
      molecules that are likely to be responsible for Schwann cell precursor survival,
      proliferation, and maturation in vivo and in vitro. Although the receptors to
      which beta neuregulins bind have been defined, little is known about the
      transcription factors these important ligands activate. Using antibodies,
      quantitative imaging methods and Western blotting, we show that beta neuregulin
      induces a high level of phosphorylation of the transcription factor cyclic AMP
      response element binding protein (CREB) on Ser-133 in cultured rat Schwann cells
      and that the phosphorylation is prolonged over several hours. In contrast,
      neurotrophins, CNTF, FGF-2, EGF, and TGFbeta induce little or no phosphorylation
      of CREB despite the fact that receptors for these factors are present on Schwann
      cells. As expected CREB phosphorylation was detected following cAMP elevation,
      and it was also induced by elevation of cytoplasmic Ca2+, endothelin 1, and PDGF
      BB. The signal was lower than that seen in response to beta neuregulin, and
      transient, unlike the sustained CREB activation induced by beta neuregulin. Our
      results suggest that the sustained phosphorylation of CREB on Ser-133 may
      contribute to the broad spectrum of effects that beta neuregulins have on cells
      of the Schwann cell lineage and that the CREB pathway may be important for
      transduction of neuregulin signals in Schwann cells. Copyright 1998 Academic
      Press.

PMID- 9618231
TI  - Maintained coupling of oxidative phosphorylation to creatine kinase activity in
      sarcomeric mitochondrial creatine kinase-deficient mice.
AB  - The importance of mitochondrial creatine kinase (mi-CK) in oxidative muscle was
      tested by studying the functional properties of in situ mitochondria in saponin
      skinned muscle fibres from sarcomeric mi-CK-deficient (mutant) mice. Biochemical
      analyses showed that the lack of mi-CK in mutant muscle was associated with a
      decrease in specific activity of MM-CK in mutant ventricle, and increase in
      mutant soleus (oxidative) muscle. Lactate dehydrogenase activity and isoenzyme
      analysis showed an increased glycolytic metabolism in mutant soleus. No change
      was observed in ventricular muscle. In control animals, the apparent K(m) of
      mitochondrial respiration for ADP in ventricle and soleus (232 +/- 36 and 381 +/-
      63 microM, respectively) was significantly reduced in the presence of creatine
      (52 +/- 8 and 45 +/- 12 microM, respectively). There was no change in the K(m) in
      oxidative fibres from mutant mice (258 +/- 27 and 399 +/- 66 microM,
      respectively) compared with control, though surprisingly, it was also
      significantly decreased in the presence of creatine (144 +/- 8 and 150 +/- 27
      microM, respectively) despite the absence of mi-CK. It is proposed that in mutant
      (and perhaps normal) oxidative tissue, cytosolic MM-CK can relocate to the outer
      mitochondrial membrane, where it is coupled to oxidative phosphorylation by close
      proximity to porin, and the adenine nucleotide translocase. Such an effect can
      preserve the functioning of the CK shuttle and the energetic properties of mi-CK
      deficient tissue.

PMID- 9618232
TI  - Adenosine A1 receptor stimulation antagonizes the negative inotropic effects of
      the PKC activator dioctanoylglycerol.
AB  - It has been suggested that adenosine cardioprotection occurs via adenosine A1
      receptor-mediated activation of protein kinase C (PKC). However, adenosine has
      well-known vasodilatory effects in the myocardium, whereas PKC is a
      vasoconstrictor. This study examined whether adenosine A1 receptor activation
      alters the effects of the PKC activator. 1,2-dioctanoyl-s,n-glycerol (DOG) in
      isolated perfused rat hearts (left-ventricular developed pressure) and rat
      ventricular myocytes ([Ca2+]i and cell shortening). Exposure to DOG decreased
      left-ventricular developed pressure by 30%, an effect that was completely
      reversible. Pretreatment of isolated hearts with either the PKC inhibitor
      chelerythrine or the adenosine A1 agonist 2-chloro-N6-cyclo-cyclo-isolated
      pentlyadenosine (CCPA) attenuated the negative inotropic effects of DOG. In the
      isolated myocytes, DOG decreased [Ca2+]i and cell shortening by 25 and 28%,
      respectively, effects that were attenuated by both chelerythrine and CCPA. The
      CCPA attenuation of the DOG-induced decrease in [Ca2+]i and cell shortening was
      blocked by pretreating the myocytes with the adenosine A1 antagonist, 8
      cyclopentyl-1,3-dipropylxanthine (DPCPX). These results indicate that in rat
      ventricular myocardium, adenosine A1 receptor activation attenuates the apparent
      PKC-dependent negative inotropic effects of DOG via preservation of [Ca2+]i
      levels.

PMID- 9618233
TI  - A thyroid hormone analog stimulates angiogenesis in the post-infarcted rat heart.
AB  - In view of the evidence that thyroid hormone administration has angiogenic
      effects on the hypertrophic myocardium, we tested the hypothesis that the
      capillary supply in the hypertrophic myocardium surviving infarction would be
      improved by administration of the thyroid hormone analog, diiodothyroproprionic
      acid (DITPA). We administered DITPA (MI-DITPA) or saline (MI-saline), s.c., to
      rats for 10 days following experimental infarction of the left ventricle (LV).
      Morphometric methods were used to assess capillarity and myocyte cross-sectional
      area in three regions of the left ventricle: (1) border (next to the scar of
      infarction); (2) adjacent (next to the border); and (3) remote (interventricular
      septum). Infarct size ranged from 20-85% of the LV free-wall, and both groups had
      similar mean infarct size. Capillary length density (LV) was significantly higher
      in the remote region of the treated group than in the MI-saline rats. LV in the
      border region, which experienced the most marked increase in cardiocyte cross
      sectional area, was not significantly lower than in the other regions, indicating
      a more marked angiogenic response. In hearts with large infarcts (> or = 40%) LV
      in the border region was higher in the DITPA group than in the non-treated rats.
      In the MI-DITPA group, cardiocyte size in the border region was positively
      correlated with that of the other regions, which contrasts with the negative
      correlations noted for the MI-saline rats. These data suggest that DITPA therapy
      (1) may improve maximal perfusion potential of the hypertrophied myocardium
      surviving a myocardial infarction, and (2) is selectively effective in the border
      region of hearts with large infarcts.

PMID- 9618234
TI  - MAP kinase mediates epidermal growth factor- and phorbol ester-induced
      prostacyclin formation in cardiomyocytes.
AB  - We studied the role of protein kinase C (PKC) and mitogen-activated protein
      kinase (MAPK) in epidermal growth factor (EGF)-induced prostacyclin (PGI2)
      production in cultured, spontaneously-beating neonatal ventricular rat
      cardiomyocytes. To this purpose, the effect of EGF on cardiomyocyte MAPK
      phosphorylation, MAPK activity and PGI2-production were investigated, and
      compared to those induced by the PKC activator 4 beta phorbol 12-myristate 13
      acetate (PMA). Both EGF (0.1 microM) and PMA (0.1 microM) induced the rapid and
      reversible phosphorylation of 42 KDa-MAPK in ventricular cardiomyocytes,
      responses that were accompanied by transient increases in MAPK activity (190-230%
      of control values within 5 min), and two- to three-fold increases in PGI2
      formation. The tyrosine kinase inhibitors lavendustin (1 microM) and genistein
      (10 microM) strongly inhibited EGF-induced MAPK activation and PGI2-formation,
      but had no effect on PMA-stimulated responses. Experiments with the PKC inhibitor
      CGP 41251 (1 microM) or with PKC-downregulated cells demonstrated that in
      contrast to the PMA-stimulated responses, EGF-induced MAPK activation and PGI2
      production were PKC-independent processes. Investigating the role of MAPK in EGF-
      and in PMA-promoted PGI2-formation, we found that the MAPK-inhibitor 6
      thioguanine (500 microM), as well as the MAPK-kinase-inhibitor PD98059 (50
      microM) abolished both EGF- and PMA-stimulated PGI2-production in cardiomyocytes.
      Our results indicate that MAPK-activation is at the basis of both growth factor
      receptor and PKC-dependent eicosanoid-formation in ventricular cardiomyocytes,
      where EGF-induced prostaglandin-production takes place via a PKC-independent
      pathway.

PMID- 9618235
TI  - Effect of collagenase on surface expression of immunoreactive fibronectin and
      laminin in freshly isolated cardiac myocytes.
AB  - The extracellular glycoproteins fibronectin (FN) and laminin (LMN) are
      ubiquitously expressed in myocardial tissue. These glycoproteins are important
      for cellular attachment and differentiation of the cardiac myocytes. Utilizing
      specific antibodies for the detection of FN and LMN, respectively, the
      distribution of these extracellular proteins was examined in enzymatically
      isolated adult cardiac myocytes. Immunofluorescence staining of rod-shaped
      cardiac myocytes revealed only remnants of immunoreactive FN on the cellular
      surface and in the transverse tubular membrane system. LMN expression, however,
      was preserved in a raster-like pattern in the cardiac myocytes. In order to study
      the distribution of these glycoproteins at high resolution, scanning electron
      microscopy using the backscattered electron mode was combined with immunogold
      staining and silver-enhancement. In addition, to confirm the immunofluorescence
      microscopic observations it was shown that FN labelling was restricted to ill
      defined extracellular material and that LMN was absent from the intercalated
      discs of the cardiac myocytes. The hypercontracted cells were characterized by
      numerous surface protrusions devoid of immunoreactive LMN. Thus, these results
      indicate that FN and LMN are differently affected by collagenase treatment, and
      that these changes of glycoprotein expression may influence the normal function
      of the cardiac myocytes as well as the membrane stability during the development
      of irreversible cellular lesions.

PMID- 9618236
TI  - Length dependence of calcium- and force-transients in normal and failing human
      myocardium.
AB  - Two questions were analysed: (1) Is the Frank-Starling mechanism operative in
      failing human myocardium? (2) Are length-dependent changes in force accompanied
      by length-dependent changes in intracellular calcium transients in human
      myocardium? METHODS: (I) in electrically stimulated left-ventricular trabeculae
      [normal donor heart (NDH), n = 8; end stage dilated cardiomyopathy (DCM), n =
      11], isometric force development was analysed as a function of muscle length (37
      degrees C, oxygenated Krebs-Henseleit solution, supramaximal electrical
      stimulation, frequency: 1 Hz). (II) Myocardium from the same patients were loaded
      with the fluorescent dye FURA-2/AM for simultaneous measurements of intracellular
      calcium transient (ICT) and force development at different muscle lengths. Muscle
      length, resting force, developed force and intracellular Calcium ("ratio method")
      were monitored continuously. RESULTS: (I) developed force increased up to an
      optimum as a function of muscle length in NDH- and DCM-myocardium. The slope of
      this increase was flatter in DCM-myocardium (P < 0.01). (II) In NDH- and DCM
      myocardium, diastolic and systolic calcium increased significantly with muscle
      length. With decreasing muscle lengths the ICT became broader, the diastolic
      decay was retarded and the peak of the ICT was flatter. At Lmax the calcium
      amplitude was 23% smaller in DCM than in NDH (P < 0.04). CONCLUSION: there is a
      clear length dependence of active force in DCM-myocardium. The length dependence
      of force development is associated with length-dependent modulations of the ICT.
      The flatter slope of the length-force curve in DCM may be partly explained by
      altered intracellular calcium handling in failing myocardium.

PMID- 9618237
TI  - Cardiac myofilament protein function is altered during sepsis.
AB  - Male Sprague-Dawley rats (350-500 g) were made septic by intraperitoneal
      injection of 200 mg/kg cecal material in 5% dextrose in water (D5W; 5 ml/kg).
      Control rats (n = 11) received D5W. Preparations were studied on days 1 (n = 7),
      3 (n = 7), and 7 (n = 8) of sepsis. In isolated hearts, ventricular function was
      depressed on days 3 and 7 of sepsis. Densitometric analysis of myofilament
      proteins from septic rats separated by SDS-PAGE showed no differences in relative
      amounts of actin, troponin, tropomyosin and myosin light chains compared to
      control. Myofilament function, assessed by measuring ATPase activities, was
      altered during sepsis. CA(2+)-independent Mg-ATPase activity was elevated on days
      1 and 3 of sepsis, returning toward control by day 7. Maximal ATPase activity was
      unchanged on day 1, but was increased on days 3 and 7 sepsis. Myofibrillar myosin
      K(EDTA)-, Ca(2+)-, and Mg(2+)-ATPase activities were not altered, nor were there
      any apparent changes in myosin heavy chain isoform populations. Our data are the
      first to demonstrate alterations in minimal and maximal ATPase activities and
      myofilament CA(2+)-sensitivity during chronic peritoneal sepsis. These
      alterations may contribute to observed changes in ventricular function.

PMID- 9618238
TI  - Reversible S-nitrosation of creatine kinase by nitric oxide in adult rat
      ventricular myocytes.
AB  - We have previously demonstrated that the nitric oxide (NO) donor S-nitroso-N
      acetylcysteine (SNAC) reversibly decreases the activity of creatine kinase (CK)
      in an isolated rat heart preparation, markedly suppressing myocardial contractile
      responsiveness to an inotropic challenge. We wished to further examine the role
      of exogenous and endogenous sources of NO species on S-nitrosation of CK and
      subsequent enzyme activity in adult rat ventricular myocytes (ARVM). Two S
      nitrosothiol groups were formed in the CK dimer after nitrosation of rabbit
      skeletal muscle CK in solution. CK inactivation due to S-nitrosation was time-
      and concentration-dependent in solution and in ARVM lysate for both NO donors S
      nitroso-N-acetylpenicillamine (SNAP) and SNAC, and was rapidly reversible with
      the sulfhydryl dithiothreitol (DTT). Similarly, SNAC or SNAP dose-dependently
      decreased CK activity in intact ARVM, which was further attenuated by increasing
      the metabolic activity of the cells with electrical pacing for 1 h. Co-cultures
      of ARVM with interleukin 1 beta (IL-1 beta)- and interferon gamma (IFN gamma)
      pretreated cardiac microvascular endothelial cells (CMEC) caused no detectable
      decline in myocyte CK activity. Increasing GSH levels attenuated the decline in
      myocyte CK activity with SNAC, while decreases in myocyte GSH levels enhanced the
      inhibitory effect of SNAC on intact myocyte CK activity. These data indicate that
      the degree of inhibition of cardiac myocyte CK by NO is dependent on the extent
      of myocyte metabolic activity and the intracellular GSH content.

PMID- 9618239
TI  - Cardiodepressant effects of interferon-gamma and endotoxin reversed by inhibition
      of NO synthase 2 in rat myocardium.
AB  - Endogenous nitric oxide (NO) signalling pathways within the myocardium depress
      myocardial contractile function in septic shock and some cardiomyopathies. We
      have explored the role of NO synthases (NOSs) in mediating the cardiodepressant
      actions of interferon-gamma (IFN-gamma) and lipopolysaccaride (LPS) in rat
      papillary muscle. Muscles from the right ventricle were electrically stimulated
      (0.2 Hz) at 30 degrees C and isometric contraction monitored. Exposure to IFN
      gamma and LPS for 15 h in vitro significantly decreased the peak tension (PT for
      IFN-gamma + LPS, from 0.13 +/- 0.03 to 0.07 +/- 0.02 g) and rate of tension
      development (dT/dt for IFN-gamma + LPS, from 1.78 +/- 0.36 to 1.17 +/- 0.28 g/s)
      compared to untreated controls, and this was prevented by dexamethasone (1
      microM) and partly reversed by a non-specific NOS inhibitor, NG-nitro-L-arginine
      (NOLA, 30 microM). Likewise, the maximum inotropic response of the papillary
      muscles to isoprenaline (0.001-10 microM) decreased significantly after 15 h
      treatment with IFN-gamma and LPS (PT from 83 +/- 18 to 28 +/- 6%; +dT/dt from 83
      +/- 12 to 31 +/- 7%; -dT/dt from 83 +/- 12 to 38 +/- 6%). Again, the depressant
      effects of IFN-gamma and LPS on inotropic responsiveness to isoprenaline were
      completely prevented by pretreatment with dexamethasone (1 microM), by a specific
      inhibitor of NOS2, mercaptoethylguanidine (MEG, 30 microM) and by NOLA. Whereas
      dexamethasone and NOLA protected against the attenuation of baseline contractions
      induced by LPS and IFN-gamma, MEG did not. Western blot analysis of cardiac
      myocytes showed that there was no constitutive expression of NOS2, but IFN-gamma
      and LPS induced expression of NOS2, and this was prevented by dexamethasone. Thus
      IFN-gamma, in the presence of LPS, reduced papillary muscle contraction and
      decreased responsiveness to beta-adrenoceptor stimulation through induction of
      NOS2 in the muscle. Increased NO production may contribute to the cardiac
      depression during septic shock and anti-cancer therapy with cytokines, and
      perhaps in heart failure.

PMID- 9618240
TI  - Glibenclamide does not prevent action potential shortening induced by ischemia in
      anesthetized rabbits but reduces ischemia-induced arrhythmias.
AB  - The possible ischemia-selective Class III anti-arrhythmic action (selective
      action potential widening in ischemia) of the IKATP blocker glibenclamide was
      assessed in anesthetized rabbits during ischemia induced by complete occlusion of
      a coronary artery. Coronary artery occlusion caused an initial prolongation in
      monophasic action potential (MAP) duration at 90% repolarization from 145 +/- 2.8
      ms (mean +/- S.E.M., n = 14) to 162 +/- 4.5 ms (P < 0.05) 1 min after ischemia.
      This was followed by a rapid and sustained shortening to 104 +/- 4.9 ms 5 min
      after the onset of ischemia (P < 0.05 from both values). Glibenclamide (3, 6, 12
      or 24 mg/kg, i.v.) caused a statistically significant, dose-related reduction in
      the rate of MAP shortening induced by ischemia, whereas 0.3 mg/kg was without
      effect. The effective dose for a 50% maximal effect (ED50) was 13 +/- 0.8 mg/kg
      (n = 28). Despite this, there was no effect on the final magnitude of MAP
      shortening. Five min after induction of ischemia, there were no longer any
      detectable effects of glibenclamide on MAP duration. Glibenclamide significantly
      reduced the incidence of ventricular fibrillation, although the effect was not
      dose related. No differences were found in the latency to ventricular
      fibrillation between groups. Ventricular fibrillation occurred 10.6 +/- 1.1 min
      (n = 19) after the start of ischemia. In a similar experiment, 0.3 mg/kg
      glibenclamide i.v. did not affect the rate of MAP shortening, the final magnitude
      of MAP shortening or the occurrence of arrhythmias caused by ischemia. Since the
      action potential widening effects of glibenclamide in ischemic tissue were not
      observed at the time when arrhythmias occurred, it is unlikely that an ischemia
      selective Class III anti-arrhythmic action contributes to the limited
      antiarrhythmic actions of glibenclamide.

PMID- 9618241
TI  - Myocytes isolated from rejecting transplanted rat hearts exhibit reduced basal
      shortening which is reversible by aminoguanidine.
AB  - Transplanted hearts exhibit depressed contractile function during periods of
      acute rejection. Myocytes from rejecting hearts also express inducible nitric
      oxide synthase (iNOS). We hypothesized that an intrinsic defect, due to the
      increased nitric oxide production by myocytes, is responsible for much of the
      observed contractile dysfunction. To test our hypothesis, we recorded shortening
      of myocytes isolated from rejecting (allograft) and non-rejecting (isograft)
      transplanted rat hearts under control conditions and following exposure to
      aminoguanidine (an inhibitor of iNOS), or methylene blue (an inhibitor of nitric
      oxide stimulation of guanylate cyclase). Four days after transplantation, basal
      shortening was reduced in allograft myocytes compared to isograft myocytes
      (allografts: 7.0 +/- 0.8 microns; isografts; 10.7 +/- 0.9 microns; P < 0.05).
      Allograft myocytes also had higher cGMP levels than isograft myocytes
      (allografts: 0.58 +/- 0.16 pmol/mg protein; isografts: 0.13 +/- 0.08 pmol/mg
      protein; P < 0.05). Aminoguanidine (1 mM) had no effect on shortening or cGMP
      levels in isograft myocytes, whereas aminoguanidine significantly reduced cGMP
      levels and greatly enhanced shortening of allograft myocytes, such that
      shortening was now similar in allograft and isograft myocytes. Methylene blue
      (100 microM) also caused a more than three-fold greater increase in shortening of
      allograft myocytes (+80 +/- 15%) than isograft myocytes (+23 +/- 6%; P < 0.05
      from allografts). These results suggest that myocytes isolated from rejecting
      hearts have a reversible intrinsic contractile depression which is mediated by
      overstimulation of the nitric oxide/cGMP pathway within the myocytes. This
      intrinsic contractile dysfunction may be a major factor responsible for the
      reversible cardiac depression associated with acute rejection of transplanted
      hearts.

PMID- 9618242
TI  - Human ventricular myocytes in vitro exhibit both early and delayed
      preconditioning responses to simulated ischemia.
AB  - Myocardial tissue has been demonstrated to exhibit, in response to brief periods
      of ischemia, both an immediate period of cytoprotection [i.e. early or "first
      window" preconditioning response (EPR)], and a later period of cytoprotection
      [i.e. delayed or "second window" preconditioning response (DPR)], when exposed to
      a subsequent prolonged hypoxic insult. EPR has been documented in vitro in
      isolated cardiac myocytes, as well as in situ in intact hearts or trabeculae, for
      a number of vertebrate species, including humans. However, there are no reports
      to date of DPR in human cardiac myocytes. To address this question, human
      ventricular myocytes (HVM) primary isolates were prepared from fetal ventricular
      muscle, grown to confluency, and studied in primary culture in serum-free medium
      (> 90%) ventricular myocytes as determined by immunohistochemical analysis with
      an anti-myosin chain antibody). Using cell viability as determined by trypan blue
      exclusion, an EPR response could readily be detected following 15, 30, or 60 min
      of simulated ischemia (SI) in a hypoxic (< 1 tau pO2) buffer containing 11 mmol/l
      2-deoxyglucose, followed by a prolonged (c. 17 h) SI challenge. In addition, HVM
      exposed to 60 min of SI, followed after 24 h by a period of SI, also exhibited a
      "second window" DPR (80 +/- 10% compared to 71 +/- 11% survival, in
      preconditioned and non-preconditioned cultures; P < 0.05; n = 18 independent
      experiments). Thus, in response to short periods of SI, human ventricular
      myocytes in vitro exhibit both "first window" and "second window" cytoprotective
      responses to subsequent, prolonged ischemic stress.

PMID- 9618243
TI  - Endotoxin and tumor necrosis factor alpha exert a similar proinflammatory effect
      in neonatal rat cardiomyocytes, but have different cardiodepressant profiles.
AB  - Bolus application of endotoxin to healthy volunteers results in reversible
      hemodynamic alterations, such as observed in septic cardiomyopathy. Currently,
      endotoxin-induced cardiodepression is mainly attributed to the endotoxin-induced
      release of proinflammatory cytokines into the circulation, particularly of tumor
      necrosis factor alpha and interleukin-1, the serum levels of these cytokines
      being enhanced in sepsis and septic shock, and also in various heart diseases. In
      this study, we report a proinflammatory effect of endotoxin (1-10 micrograms/ml,
      24-h incubation period) on neonatal rat cardiomyocytes in serum-free culture,
      evidenced by induction of inducible nitric oxide synthase, enhanced release of
      nitrite (protein synthesis-dependent) and interleukin-6 into the supernatant, as
      well as an increase in cell-associated interleukin-1 and a specific
      cardiodepressant profile: endotoxin disrupts beta-adrenoceptor-mediated increase
      in pulsation amplitude, but alpha-adrenoceptor-induced increase in pulsation
      amplitude and arrhythmias are not suppressed. In the presence of dexamethasone
      (0.1 microM), the endotoxin-mediated blockade of beta-adrenergic responsiveness,
      as well as induction of inducible nitric oxide synthase, enhanced nitrite release
      and interleukin-1/-6-production are inhibited. In contrast, tumor necrosis factor
      alpha at a low concentration (10 U/ml) depresses alpha- and beta-adrenergic
      responsiveness in the presence of dexamethasone in a nitric oxide-independent
      manner. These data suggest a stimulatory effect of endotoxin on the cardiomyocyte
      and a specific proinflammatory and nitric oxide-dependent cardiodepressant
      profile of endotoxin.

PMID- 9618244
TI  - Enhanced vasorelaxation by overexpression of beta 2-adrenergic receptors in large
      arteries.
AB  - This study was designed to determine if adenoviral-mediated delivery of a
      transgene encoding the beta 2-adrenergic receptor (beta 2-AR) to the carotid
      arterial wall could result in alterations in in vivo vascular function. De
      endothelialized rat carotid arteries were infused in vivo with 0.1 mg/ml elastase
      and adenovirus [6 x 10(9) plaque forming units (PFU)] containing either the
      marker gene beta-galactosidase (Adeno-beta-gal), DNA encoding the human beta 2-AR
      (Adeno-beta 2-AR), or no transgene. This low concentration of elastase increased
      the water permeability (5.2 +/- 0.6 v 1.9 +/- 0.4 x 10(-8) cm/s/mmHg, n = 4, P <
      0.0001) without affecting either the vasomotor responsiveness or the morphology
      of the arterial wall. A transfection efficiency of 73% was achieved with Adeno
      beta-gal (n = 3). beta-gal expression was associated with infrequent appearance
      of T and B lymphocytes, or neutrophil infiltration. Five days after infection
      with Adeno-beta 2-AR, the total beta-AR density increased six-fold (67.8 +/- 3.4
      v 397.0 +/- 155.5 fmol/mg protein, n = 5, P < 0.01); isoproterenol-induced
      vasorelaxation at transmural pressures from 10-110/mmHg increased (P < 0.01)
      compared to arteries exposed to control virus (empty adenovirus), n = 4; and
      isoproterenol-stimulated cAMP production was increased by 65% (n = 5). Thus,
      adenoviral-mediated delivery of beta 2-ARs into large artery walls results in
      enhanced beta-AR-mediated vasorelaxation via augmentation in cAMP levels in
      vascular smooth muscle cells.

PMID- 9618245
TI  - Role of microtubules in the contractile dysfunction of myocytes from tachycardia
      induced dilated cardiomyopathy.
AB  - Microtubules of cardiac myocytes are increased in pressure-overloaded cardiac
      hypertrophy, which interfere with the actin-myosin crossbridge motion and depress
      muscle contractility. However, it is unknown whether microtubules are increased
      in non-hypertrophied, dilated cardiomyopathy and, if so, their increase could
      contribute to the depressed contractility. We assessed the contractile function
      of isolated left-ventricular (LV) myocytes and also quantitated tubulin mRNA
      levels as well as free and polymerized tubulin proteins using the LV myocardium
      obtained from dogs with rapid pacing (240 beats/min, 4 weeks)-induced dilated
      failing cardiomyopathy (HF; n = 6) and control dogs (n = 6). Myocyte
      contractility was significantly depressed in HF compared to control. Northern
      blot analysis indicated that tubulin mRNA levels (normalized to GAPDH mRNA) in HF
      dogs were upregulated (0.43 +/- 0.04 v 0.13 +/- 0.02; P < 0.01). In contrast, the
      amount of total tubulins (633 +/- 52 v 697 +/- 42 micrograms/g wet weight; P =
      N.S.) and the ratio of polymerized tubulin fraction-to-total tubulin (0.44 +/-
      0.02 v 0.44 +/- 0.01; P = N.S.) did not differ between the two groups.
      Immunohistochemical studies showed no apparent differences in the distribution or
      density of intracellular microtubule network. Further, the exposure of myocytes
      to colchicine (1 mumol/l, 30 min), which depolymerizes microtubules, did not
      promote any improvement of the depressed myocyte contraction. Pacing-induced
      tachycardia increased myocardial tubulin mRNA, but the amount of total and
      polymerized tubulins were not increased, indicating that alterations in myocyte
      microtubules do not contribute to the contractile abnormalities in this model of
      HF.

PMID- 9618246
TI  - Transgenic A1 adenosine receptor overexpression markedly improves myocardial
      energy state during ischemia-reperfusion.
AB  - A1 adenosine (A1AR) activation may reduce ischemia-reperfusion injury. Metabolic
      and functional responses to 30 min global normothermic ischemia and 20 min
      reperfusion were compared in wild-type and transgenic mouse hearts with
      approximately 100-fold overexpression of coupled cardiac A1ARs. 31P-NMR
      spectroscopy revealed that ATP was better preserved in transgenic v wild-type
      hearts: 53 +/- 11% of preischemic ATP remained after ischemia in transgenic
      hearts v only 4 +/- 4% in wild-type hearts. However, recovery of ATP after
      reperfusion was similar in transgenic (46 +/- 5%) and wild-type hearts (37 +/-
      12%). Reductions in phosphocreatine (PCr) and cytosolic pH during ischemia were
      similar in both groups. However, recovery of PCR on reperfusion was higher in
      transgenic (67 +/- 8%) v wild-type hearts (36 +/- 8%), and recovery of pH was
      greater in transgenic (pH = 7.11 +/- 0.05) v wild-type hearts (pH = 6.90 +/-
      0.02). Bioenergetic state ([ATP]/[ADP].[Pi]) was higher in transgenic v wild-type
      hearts during ischemia-reperfusion. Time to ischemic contracture was prolonged in
      transgenic (13.6 +/- 0.8 min) v wild-type hearts (10.4 +/- 0.3 min). Degree of
      contracture was lower and recovery of function in reperfusion higher in
      transgenic v wild-type hearts. In conclusion, A1AR overexpression reduces ATP
      loss and improves bioenergetic state during severe ischemic insult and
      reperfusion. These changes may contribute to improved functional tolerance.

PMID- 9618247
TI  - Identification of a recurrent missense mutation in the Norrie disease gene
      associated with a simplex case of exudative vitreoretinopathy.
AB  - Disorders such as Norrie disease, X-linked familial exudative vitreoretinopathy,
      retinopathy of prematurity and X-linked primary vitreoretinal dysplasia have very
      similar clinical manifestations. They exhibit retinal fold, retinal detachment,
      retinal traction and the formation of retrolental fibrovascular membrane. In
      order to identify carriers for these disorders and provide precise genetic
      counseling of the relatives, a molecular genetic analysis will be helpful. This
      report describes the results of Norrie disease analysis in simplex cases of
      exudative vitreoretinopathy. the identification of a recurrent mutation in the
      Norrie disease gene in a simplex case of exudative vitreoretinopathy further
      strengthens the notion that Norrie disease and exudative vitreoretinopathy are
      allelic disorders.

PMID- 9618251
TI  - The dual coated pit pathway hypothesis: vertebrate cells have both ancient and
      modern coated pit pathways for receptor mediated endocytosis.

PMID- 9618252
TI  - Isolation and characterization of PDE8A, a novel human cAMP-specific
      phosphodiesterase.
AB  - As part of our efforts to understand the regulation of intracellular cAMP and to
      generate new targets for pharmacological intervention, we have cloned and
      characterized the first isozyme in a new family of cyclic nucleotide
      phosphodiesterases, PDE8A. PDE8A is most similar to PDE4 (38.5% amino acid
      identity in the catalytic domain), but is clearly not a member of any of the
      seven known PDE families. We report the cloning of human cDNA encoding the C
      terminal 713 amino acids of the protein, including a 283 amino acid region
      located near the C-terminus that is homologous to the approximately 270 amino
      acid catalytic domain of other PDEs. In addition, we found cDNA sequences
      consistent with alternative 5' mRNA splicing analogous to that seen in other PDE
      genes. PDE8A is expressed in a wide variety of tissues as a approximately 4.5 kb
      mRNA, with highest levels in testis, ovary, small intestine, and colon. The C
      terminal 545 amino acids of PDE8A (the region shared among all splice variants)
      were expressed in baculovirus. Kinetic analysis of the baculovirus expressed
      enzyme shows it to be a very high affinity cAMP specific PDE with a Km of 55 nM
      for cAMP and 124 microM for cGMP. The Vmax (150 pmol/min/microgram recombinant
      enzyme) is about 10 times slower than that of PDE4. The cAMP hydrolytic activity
      of PDE8A is not modulated by cGMP at concentrations up to 100 microM. The enzyme
      requires the presence of at least 1 mM Mn2+ or Mg2+ for maximal activity in
      vitro, while 100 mM Ca2+ restores only about 20% activity. PDE8A is insensitive
      (up to 100 microM) to a variety of PDE inhibitors including rolipram, zaprinast,
      vinpocetine, SKF-94120, and IBMX, but is inhibited (IC50 = 9 microM) by the PDE
      inhibitor dipyridimole. To give PDE8A a descriptive name that distinguishes it
      from the other two known high affinity cAMP-specific phosphodiesterases (PDE4 and
      PDE7), we denote PDE8A as the high affinity cAMP-specific and IBMX-insensitive
      PDE.

PMID- 9618253
TI  - The detection of cytochrome P450 2E1 and its catalytic activity in rat testis.
AB  - Cytochrome P450 2E1 participates in the bioactivation of a wide variety of
      environmental and occupational pollutants. Such reactions may lead to the
      production of active carcinogenic metabolites. The presence of P450 2E1 in the
      testis and prostate has not yet been reported. In the present study, cytochrome
      P450 2E1 mRNA has been identified in the rat prostate and testis by reverse
      transcription PCR, southern blotting, and DNA sequencing. P450 2E1 protein from
      rat testis could be detected with immunoblot analysis, but was not detected in
      the prostate. The hydroxylation of p-nitrophenol, known to be mediated by P450
      2E1, was demonstrated by HPLC measurement of product formation in microsomal
      fractions from the rat testis, but again not from prostate. Exposure of rats to
      pyridine resulted in a 2.9-fold increase of p-nitrophenol hydroxylation by
      testicular microsomes. Diethyldithiocarbamate, a selective mechanism-based
      inhibitor of P450 2E1, or a P450 2E1 monoclonal antibody, caused marked
      inhibition of testicular microsomal p-nitrophenol hydroxylase activity. These
      results indicate that cytochrome P450 2E1 is present in the rat testis, and that
      it is elevated by the treatment of the animals with pyridine. Thus, the presence
      and inducibility of cytochrome P450 2E1 in the testis may be of significance in
      the bioactivation of environmental chemicals to genotoxic metabolites.

PMID- 9618254
TI  - Relationship between adenovirus-mediated aquaporin 1 expression and fluid
      movement across epithelial cells.
AB  - AdhAQP1, a recombinant adenovirus encoding the human water channel aquaporin 1
      (AQP1), has been shown to be useful for gene therapy of salivary glands rendered
      hypofunctional following irradiation. Here we utilized AdhAQP1 to examine the
      relationship between AQP1 expression and fluid movement across a polarized
      salivary epithelial cell monolayer. In response to a 440 to 340 mosm gradient,
      net fluid movement across cells infected with AdhAQP1 was approximately 10-fold
      that seen in uninfected cells or cells infected with a control virus. At a
      multiplicity of infection (MOI) of 5, fluid movement was linear for 15-30 min.
      Increasing the osmotic gradient resulted in a proportional increase in fluid
      movement. At low virus MOIs (0.1-1.0), fluid movement was markedly enhanced
      relative to that seen at higher MOIs (approximately 5.10), where the level of
      AQP1 expression and number of cells transduced were considerably greater. We
      conclude that significant, osmotically-obliged fluid movement in a salivary cell
      monolayer with low basal water permeability does not require high levels of AQP1
      expression.

PMID- 9618255
TI  - cDNA sequence, transport function, and genomic organization of human OCTN2, a new
      member of the organic cation transporter family.
AB  - We have cloned OCTN2, a new member of the organic cation transporter family, from
      a human placental trophoblast cell line. The hOCTN2 cDNA codes for a protein of
      557 amino acids with twelve putative transmembrane domains. The octn2 gene,
      located on human chromosome 5q31, consists of ten exons. The OCTN2-specific
      transcript, 3.5 kb in size, is expressed widely in human tissues and in cell
      lines of human origin. At the level of amino acid sequence, OCTN2 is more closely
      related to OCTN1 than to OCT1, OCT2 and OCT3. When expressed heterologously in
      HeLa cells, OCTN2 mediates the transport of tetraethylammonium, a prototypical
      organic cation, in a pH-dependent manner. Several organic cations, including the
      neurotoxins 1-methyl-4-phenylpyridinium, 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine, and methamphetamine, compete for the OCTN2-mediated transport
      process.

PMID- 9618256
TI  - Complete amino acid sequence of the B chain of mistletoe lectin I.
AB  - The primary structure of the B chain of mistletoe lectin I, the component of a
      commercially available extract from Viscum album exhibiting immunomodulatory
      capacity, was established based on amino acid sequence analysis of the protein
      and peptides derived from its enzymatic digestion. It is composed of 264
      residues, including seven cysteine residues and three N-linked carbohydrate
      chains. The amino acid sequence of MLB shows a high homology with those from
      other structurally related galactoside-specific lectins such as ricin and abrin
      with 169 and 146 identities, respectively. These results are of crucial
      importance in order to understand the biological activity of ML-1.

PMID- 9618257
TI  - The flavoprotein component of the Escherichia coli sulfite reductase can act as a
      cytochrome P450c17 reductase.
AB  - The flavoprotein component (SiR-FP) of the E. coli sulfite reductase was found to
      support 17 alpha-hydroxylation of pregnenolone in the presence of cytochrome
      P450c17. Half maximum activity is obtained for a 1:1 ratio of SiR-FP, expressed
      as monomer concentration, to P450c17. When compared to bovine NADPH-cytochrome
      P450 reductase, SiR-FP is about 12-15 times less efficient. P450c17 was
      demonstrated to interact specifically with the FMN-binding domain of the protein
      and the N-terminal part of SiR-FP is suspected to play a role in electron
      transfer. A cluster of negatively charged residues was found in SiR-FP by amino
      acid sequence comparison with rat cytochrome P450 reductase. These results argue
      in favour of the flavodoxin origin of the FMN-binding domain of SiR-FP.

PMID- 9618258
TI  - Measurement of altered aspartyl residues in the scrapie associated form of prion
      protein.
AB  - In transmissible spongiform encephalopathies (TSE), the endogenous protease
      sensitive prion protein (PrP-sen) of the host is converted to a pathologic form
      (PrP-res) that has greatly enhanced proteinase K resistance, insolubility, and
      beta sheet content. To investigate the possibility that alterations at aspartyl
      or asparaginyl residues in the form of D-aspartate and/or L-isoaspartate could
      play a role in either the formation or stabilization of PrP-res in TSE-infected
      animals, we assayed for the presence of these abnormal residues in PrP-res.
      Protein D-aspartyl/L-isoaspartyl carboxyl methyltransferase (PIMT) was used to
      methylate and radiolabel altered aspartyl residues, which were detected in PrP
      res, but at low levels (0.5 mole%). The scarcity of D-aspartyl and/or L
      isoaspartyl groups in PrP-res suggests that this modification is unlikely to be
      primarily responsible for the differences between PrP-res and PrP-sen. However,
      it remains possible that such modifications in substoichiometric numbers of PrP
      molecules could help to initiate the PrP-res formation or stabilize PrP-res
      polymers in vivo.

PMID- 9618259
TI  - Equilibrium intermediates in the unfolding pathway of creatine kinase.
AB  - The unfolding of creatine kinase in various concentrations of guanidine
      hydrochloride of increasing concentrations has been investigated by combination
      of size-exclusion chromatography (SEC) with other methods. There are two peaks in
      the profiles of SEC in GuHCl at moderate concentrations, showing that unfolding
      of creatine kinase goes through dimeric and monomeric intermediates with
      increasing guanidine hydrochloride concentrations. Both intermediates have
      relatively compact structure and retain considerable ordered structure.

PMID- 9618260
TI  - Intracellular retention and degradation of tissue-nonspecific alkaline
      phosphatase with a Gly317-->Asp substitution associated with lethal
      hypophosphatasia.
AB  - One point mutation which converts glycine-317 to aspartate of tissue-nonspecific
      alkaline phosphatase (TNSALP) was reported to be associated with lethal
      hypophosphatasia (Greenberg, C. R., et al. Genomics 17, 215-217, 1993). In order
      to define the molecular defect of TNSALP underlying the pathogenesis of
      hypophosphatasia, we have examined the biosynthesis of TNSALP with a Gly317-->Asp
      substitution. When expressed in COS-1 cells, the mutant did not exhibit alkaline
      phosphatase activity at all, indicating that the replacement of glycine-317 with
      aspartate abolishes the catalytic activity of TNSALP. Pulse-chase experiments
      showed that the newly synthesized mutant failed to acquire Endo H-resistance and
      to reach the cell surface. Interestingly, this TNSALP mutant was found to form a
      disulfide-bonded high-molecular-mass aggregate and was rapidly degraded within
      the cell, though the mutant protein was modified by glycosylphosphatidylinositol
      (GPI). Lactacystin, an inhibitor of the proteasome, obstructed the degradation of
      the mutant protein, suggesting the involvement of proteasome as a part of quality
      control of TNSALP.

PMID- 9618261
TI  - Osmotic stress in viable Escherichia coli as the basis for the antibiotic
      response by polymyxin B.
AB  - Cationic antimicrobial peptides, such as polymyxin B (PxB), below growth
      inhibitory concentration induce expression of osmY gene in viable E. coli without
      leakage of solutes and protons. osmY expression is also a locus of hyperosmotic
      stress response induced by common food preservatives, such as hypertonic NaCl or
      sucrose. High selectivity of PxB against Gram-negative organisms and the basis
      for the hyperosmotic stress response at sublethal PxB concentrations is
      attributed to PxB-induced mixing of anionic phospholipid between the outer layer
      of the cytoplasmic membrane with phospholipids in the inner layer of the outer
      membrane. This explanation is supported by PxB-mediated rapid and direct exchange
      of anionic phospholipid between vesicles. This mechanism is consistent with the
      observation that genetically stable resistance against PxB could not be induced
      by mutagenesis.

PMID- 9618262
TI  - Polymorphism in the 3' untranslated region of MTG8 is associated with obesity in
      Pima Indian males.
AB  - Obesity has a genetic component and predisposes for the development of type 2
      diabetes mellitus. One approach to identifying new candidate genes for obesity is
      to explore potential regulatory factors expressed in fat tissue that may play a
      role in adipocyte development or metabolic control. Because we found relatively
      abundant mRNA levels of the putative transcription factor MTG8 in human adipose
      tissue, a polymorphic microsatellite marker in the 3' untranslated region of this
      gene was genotyped in 281 Pima Indians, a population with one of the highest
      reported rates of obesity. We detected a male-specific association with age
      adjusted percentage body fat (p = 0.0002), body mass index (p = 0.01), waist
      circumference (p = 0.008), and thigh circumference (p = 0.02). Comparative
      analysis of all 13 MTG8 exons in 30 Pimas did not reveal any genetic variants
      which could explain the association with obesity in males.

PMID- 9618263
TI  - Cloning and characterization of human Jak-2 kinase: high mRNA expression in
      immune cells and muscle tissue.
AB  - We report on the cloning and sequence analysis of the mRNA coding for full-length
      human Janus kinase 2 (Jak2). The human form of Jak2 is 1132 amino acids in length
      with a M(r) of 131 KDa. It has 95% sequence similarity to pig and rat Jak2. The
      highest level of mRNA expression was found in the spleen, peripheral blood
      leukocytes, and testis. Also a significantly high level of Jak2 mRNA was found in
      heart and skeletal muscle. Northern blot analysis showed three mRNA species in
      all tissues tested, except heart and skeletal muscle, of 7.6, 5.9, and 4.8 Kb. In
      skeletal muscle and heart, three mRNA species of 7.6, 4.8, and 3.9 Kb were
      identified. The catalytic domain of the human Jak2 was expressed and its
      specificity for phosphorylating peptide substrates derived from the gp130, STAT,
      and Jak3 molecules was determined and compared to that for human Jak1 and Jak3.

PMID- 9618264
TI  - Random inheritance of the replication complex by one of two daughter lambda
      plasmid copies after a replication round in Escherichia coli.
AB  - There are two pathways for replication of plasmids derived from bacteriophage
      lambda (so-called lambda plasmids) in Escherichia coli. One pathway is based on
      the assembly of the new replication complex at ori lambda, and the second
      requires activity of the replication complex inherited by one of two daughter
      plasmid copies after each replication round. Although these two replication
      pathways proceed at the same time in the host cell, we previously found
      conditions for specific elimination of the pathway based on the assembly of the
      new replication complex; thus, replication is restricted to that carried out by
      the heritable replication complex. These conditions are (i) the relaxed response
      to amino acid starvation and (ii) temperature upshift of the culture of cells
      harboring the lambda crotsPts1 plasmid. Here we asked whether the replication
      complex is inherited randomly by one of two daughter plasmid copies or whether
      the inheritance is preferred by one particular copy, that containing the parental
      DNA r strand or that bearing the l strand. We performed density shift experiments
      which allowed us to separate plasmid DNA molecules replicated by the heritable
      replication complex from those devoid of the replication complex and therefore
      not able to replicate. Then, [3H]thymidine-labelled plasmid DNA strands were
      separated and hybridized to membrane-bound ssDNA containing a fragment of either
      the r or l strand of lambda DNA. We found roughly equal efficiency of
      hybridization to both r and l strands in all experimental systems used.
      Therefore, we conclude that the lambda replication complex is randomly inherited
      by one of two daughter plasmid copies rather than preferentially inherited by
      either the copy carrying the parental r strand or that containing the l strand.

PMID- 9618265
TI  - Effects of tocotrienol on the intracellular translocation and degradation of
      apolipoprotein B: possible involvement of a proteasome independent pathway.
AB  - gamma-Tocotrienol (gamma-T3), a HMG CoA reductase inhibitor, was previously shown
      to stimulate the intracellular degradation of apolipoprotein B (apoB) in HepG2
      cells. The aim of this study was to explore the effects of gamma-T3 on the
      proteasome dependent co-translational degradation and the proteasome independent
      post-translational degradation of apoB. Previous studies have shown that apoB
      translocation across the endoplasmic reticulum (ER) membrane governs the co
      translational degradative pathway of apoB. Therefore, we first examined the
      effects of gamma-T3 on this pathway using a specific translocation assay derived
      from HepG2 cells. Our results indicated that gamma-T3 reduced the efficiency of
      apoB translocation across the ER membrane, suggesting that co-translational
      degradation may be partially involved. Evidence of an ER associated post
      translational degradation was also provided upon pre-treating digitonin
      permeabilized HepG2 cells with a proteasome inhibitor, lactacystin. When chased
      for 2h, ER degradation of apoB was observed and was further enhanced in the
      presence of gamma-T3 versus untreated control, in spite of proteasome inhibition.
      Combined with the ability of ALLN, a proteasome and cysteine protease inhibitor,
      to block the post-translational degradation of apoB, the data suggest that gamma
      T3 diverted more apoB to a cytosolic proteasomal dependent and possibly an ER
      associated proteasomal independent degradation pathways.

PMID- 9618266
TI  - Identification of a new member of transforming growth factor-beta superfamily in
      Drosophila: the first invertebrate activin gene.
AB  - Activins, a subgroup of the transforming growth factor-beta (TGF-beta)
      superfamily, have been extensively studied in vertebrates for their roles in
      growth and development. However, activins are not thought to be expressed in
      invertebrates. The identification of the first invertebrate activin gene is
      reported here. A genomic clone representing 102 F region of the Drosophila
      chromosome 4 is found to encode a putative activin beta. The predicted protein
      sequence has a multibasic protease site that would generate a mature C-terminal
      peptide containing 113 amino acids showing > 60% similarity to the vertebrate
      activin beta B (inhibin beta B) sequences. A TGF-beta family signature as well as
      all 9 cysteine residues conserved in the vertebrate activins are also present in
      this mature peptide sequence. Northern blot and RT-PCR analyses indicated that
      the activin beta gene is expressed in embryo, larva and adult stages of
      Drosophila.

PMID- 9618267
TI  - Identification of a unique domain in bovine brain GABAA receptors that is
      photoaffinity labelled by [3H]Ro15-4513.
AB  - We have used photoaffinity labelling and protein cleavage techniques to identify
      the site of photoincorporation of [3H]Ro15-4513 into the alpha subunit of the
      bovine gamma-aminobutyric acid type A (GABAA) receptor. Bovine brain membranes
      were photoaffinity labelled with [3H]Ro15-4513 and after solubilization and
      denaturation, proteins were specifically cleaved at either cysteine or tryptophan
      residues. Peptides were resolved by sodium dodecyl sulphate polyacrylamide gel
      electrophoresis. Cleavage at cysteine residues generated a labelled peptide of Mr
      6.5K, while cleavage at tryptophan residues generated a labelled peptide with an
      Mr of 5K. Cleavage products of this size indicate that the site of [3H]Ro15-4513
      incorporation occurs between the end of the first transmembrane domain and the
      first four amino acids of the third transmembrane domain (residues 247-289). This
      region of the GABAA receptor has not previously been implicated in the formation
      of the benzodiazepine binding site and may be part of a unique recognition domain
      for inverse agonists.

PMID- 9618268
TI  - Enhanced collagen accumulation following direct transfection of the inducible
      nitric oxide synthase gene in cutaneous wounds.
AB  - Inducible nitric oxide synthase (iNOS) is expressed during cutaneous wound
      repair. Mounting evidence suggests that wound nitric oxide (NO) augments collagen
      accumulation. We hypothesized that in vivo transfection of wound cells with the
      iNOS gene would increase physiological wound NO levels and thus augment collagen
      accumulation. Polyvinyl alcohol sponges were instilled with a mammalian
      expression plasmid (pMP6) containing either the chloramphenicol acetyl
      transferase (CAT) reporter or murine iNOS gene driven by a CMV immediate-early
      promoter. Plasmid DNA was injected alone or in complex with cationic liposomes,
      and the sponges were placed subcutaneously in male Sprague-Dawley rats which had
      received a longitudinal dorsal midline incision. Animals were sacrificed at
      different time points post-wounding and the sponges assayed for CAT activity,
      transfected iNOS mRNA, total nitrate and nitrite concentration (NOx) (as an index
      of wound NO synthesis), and hydroxyproline content (as an index of sponge
      collagen accumulation). The results demonstrate that wound cells were more
      efficiently transfected by naked DNA than by liposome mediated transfection and
      that maximal expression of both iNOS and CAT occurred at 48 hrs with a rapid
      decline after this time point. After 7 days, iNOS transfected sponges had
      accumulated significantly more collagen than those transfected with CAT. We
      conclude that cutaneous wounds can be successfully transfected by direct
      injection of naked DNA and that increased iNOS expression precedes an increase in
      collagen synthesis.

PMID- 9618269
TI  - Leptin regulation of peroxisome proliferator-activated receptor-gamma, tumor
      necrosis factor, and uncoupling protein-2 expression in adipose tissues.
AB  - It has previously been reported that intracerebroventricular (i.c.v.)
      administration of leptin induced adipose tissue apoptosis in addition to
      influencing lipid metabolism. The objective of the present study was to determine
      if the expressions of peroxisome proliferator-activated receptor-gamma (PPAR
      gamma), uncoupling protein-2 (UCP2), and tumor necrosis factor (TNF alpha) were
      influenced by in vivo leptin treatment. Expression of PPAR gamma, UCP2, and TNF
      alpha in epididymal fat tissue was examined by Western immunoblot and in situ
      immunocytochemical analysis after 5 days of i.c.v. leptin treatment. Young and
      old rats (3 and 8 months old) were treated with or without 5 micrograms/d leptin.
      Leptin treatment increased PPAR gamma expression by 70-80% (P < 0.01) in both age
      groups. Leptin treatment decreased the expression of UCP2 (P < 0.01) in young
      rats, whereas it increased UCP2 expression (P < 0.01) in old rats. Leptin
      treatment also decreased TNF alpha expression by 40% (P < 0.01) in young rats but
      did not influence its expression in old rats. The basal level of expression of
      PPAR gamma was greater in 3-month-old rats than in 8-month-old rats. The basal
      level of UCP2 and TNF alpha expression was not different between the two age
      groups. These immunoblotting data were further confirmed by in situ
      immunocytochemical analysis. The present study suggests that expression of PPAR
      gamma may be directly involved in the leptin-induced adipocyte apoptosis signal
      pathway, whereas UCP2 and TNF alpha may play roles in the leptin-induced
      lipolysis process.

PMID- 9618270
TI  - Genomic cloning and characterization of the mouse POZ/zinc-finger protein ZF5.
AB  - We isolated genomic DNA containing the entire sequence of ZF5, which was
      originally identified by its ability to repress the mouse c-myc promoter and
      which was characterized as one of the POZ (Poxvirus and zinc finger) proteins.
      The POZ motif is a protein-protein interaction interface found at the N-terminal
      region of zinc finger proteins. Sequence analysis demonstrated that the ATG
      translation initiation codon was separately located from the remainder of the
      coding sequence. Using both RNase protection and primer extension assay, a single
      major transcription start site was determined. Promoter analysis by transient
      transfection assay suggested positive autoregulation by ZF5 itself. The ZF5 N
      terminal region, including the POZ domain, was required for this regulation. Sp1
      also activated the ZF5 promoter and this activity was repressed by addition of
      ZF5. ZF5 expression was stronger in mouse ovary, lung and brain than in other
      organs.

PMID- 9618271
TI  - Identification of the critical portions of the human IL-4 receptor alpha chain
      for activation of STAT6.
AB  - Interleukin-4 (IL-4) has been shown to activate Janus kinase (Jak)-1 and Jak-3,
      followed by activation of STAT (signal transducers and activators of
      transcription) 6. This Jak-STAT pathway is central to the initiation of IL-4
      activities. In this study, we identified the essential region for the
      proliferation signal and activation of Jak-1, Jak-3, and STAT6 in the cytoplasmic
      domain of the human IL-4 receptor alpha chain (hIL-4R alpha) using a mouse T cell
      line CTLL-2. We found that the region between amino acid 353 and 393 is critical
      for the proliferation signal and activation of STAT6, but not for tyrosine
      phosphorylation of Jaks. These results suggest that in addition to the "Box-1"
      portion, which is known to be essential for Jak-1 activation, the more membrane
      distal region of hIL-4R alpha is also necessary for activation of STAT6.

PMID- 9618272
TI  - Purification and characterization of the active-site-mutated recombinant human mu
      calpain expressed in baculovirus-infected insect cells.
AB  - Recombinant human mu-calpain whose active site Cys-115 was substituted with Ser
      was expressed in insect cells using baculovirus system. The mutant mu-calpain,
      purified using an affinity-column of calpastatin oligopeptides, had no
      proteolytic activities of autolysis and caseinolysis. The large subunit of the
      mutant mu-calpain was processed from the 80 kDa form to the 76 kDa form by the
      wild type calpain, supporting the intermolecular cleavage mechanism of procalpain
      during activation. Fluorescence polarization analysis revealed that the mutant mu
      calpain retained high affinity toward fluorescein-labeled calpastatin domain 1.
      Fragmentation of the full-length calpastatin by the wild type calpain was
      enhanced by pre-incubating the inhibitor with the mutant calpain. The recombinant
      mutant calpain was suggested to retain the integrity of the high ordered
      structure of the wild type calpain.

PMID- 9618273
TI  - Requirement for membrane lipid peroxidation in HIV-1 gp120-induced neuroblastoma
      cell death.
AB  - The HIV-1 envelope protein gp120 engenders Ca(2+)-mediated, excitotoxic damage of
      rodent neuronal and human neuroblastoma cells in culture. Here we report that
      human CHP100 neuroblastoma cells undergo early peroxidation of membrane lipids
      following a brief exposure to gp120. This effect is prevented by preincubating
      cell cultures with the 21-aminosteroid U-74389G, an inhibitor of membrane lipid
      peroxidation, which also rescues neuroblastoma cultures from gp120-induced cell
      death; conversely, no protection from cell death is observed when the 21
      aminosteroid is added to neuroblastoma cultures after the induction of membrane
      lipid peroxidation by gp120. These data indicate that membrane lipid peroxidation
      has a causative role in the expression of cell death produced by the viral
      protein.

PMID- 9618274
TI  - Effect of microtubule disruption on cell adhesion and spreading.
AB  - Microtubules have been involved in a variety of cellular processes. In this
      study, we examined the role of the microtubular system in the adhesion and
      spreading of the adenocarcinoma cell line HT29-D4. Disruption of microtubules by
      nocodazole or navelbine resulted in an increase in cell adhesion to purified ECM
      proteins. This enhanced cell adhesion is mediated by integrins, but is not
      attributable to quantitative changes in the number of integrin receptors at the
      cell surface, as determined by flow cytometric analysis. In contrast to
      attachment, spreading of HT29-D4 cells was reduced by nocodazole treatment in a
      dose-dependent manner. Thus, microtubule depolymerization appears to increase
      initial attachment of cells to extracellular matrix, while impeding subsequent
      cell spreading.

PMID- 9618275
TI  - Characterization of the enhancer-like okadaic acid response element region of the
      cyclin-dependent kinase 1 (p34cdc2) promoter.
AB  - Expression of the cdk1 (p34cdc2) gene is enhanced 5-10 fold as cells re-enter the
      cell cycle from quiescence in response to serum-refeeding or following exposure
      to the protein phosphatase 1/2A inhibitor okadaic acid. Transient transfection
      analysis of nested deletions of the human cdk1 promoter identified regions that
      confer sensitivity to okadaic acid on a CAT-reporter gene. Putative okadaic acid
      response elements (OARE) were located between nt -942 to -763 (Site I) and nt 
      416 to -186 (Site II) before transcription start. The Site I element has enhancer
      like characteristics as activity is independent of sequence orientation. Mobility
      shift analysis of Site I revealed the presence of 2 high molecular weight
      complexes, one of which was enhanced in the presence of okadaic acid-treated cell
      extracts. Site I contained several sequence motifs with conserved homology to
      heat shock response element core sequences and homeobox protein binding sites.
      Site II contained a myb-binding site, a G1/S phase enhancer, and 2 retinoblastoma
      response elements flanking an E2F binding site. Enhancement of cdk1 expression
      appears dependent on 2 nonhomologous okadaic acid-sensitive promoter regions.

PMID- 9618276
TI  - The protective effect of vitamin E, idebenone and reduced glutathione on free
      radical mediated injury in rat brain synaptosomes.
AB  - In the present study the effect of ascorbate (0.8 mM)/iron (2.5 microM) on lipid
      and protein oxidation, in Synaptosomes isolated from rat brain cortex, was
      evaluated. Vitamin E, idebenone and reduced glutathione were used as free
      radicals scavengers, in order to analyze the mechanism involved in ascorbate/iron
      induced oxidative stress. An increased formation of reactive oxygen species (ROS)
      in the cytosol and in the mitochondria was observed, in ascorbate/iron treated
      synaptosomes. Idebenone (50 microM) prevented the increased formation of ROS in
      both synaptosomal compartments, vitamin E (150 microM) protected partially this
      formation in mitochondria, whereas reduced glutathione (250 microM) (GSH) was
      ineffective. After ascorbate/iron treatment an increase in lipid peroxidation
      occurred as compared to control, which was completely inhibited by idebenone. A
      decrease in protein-SH content was also observed, and it was prevented by Vitamin
      E, idebenone and GSH. When synaptosomes were treated with ascorbate/iron the
      levels of GSH decreased, and the levels of oxidized glutathione (GSSG) increased
      as compared to controls under these conditions. Glutathione peroxidase activity
      was unchanged, whereas an inhibition of glutathione reductase activity was
      observed. These data suggest that the increased formation of free radicals in
      synaptosomes leads to lipid and protein oxidation, the role of the endogenous GSH
      being essential to protect protein thiol-groups against oxidative damage in order
      to maintain enzyme activity.

PMID- 9618277
TI  - Manipulation of metallothionein expression in the regenerating rat liver using
      antisense oligonucleotides.
AB  - Metallothioneins (MTs) are low molecular weight, zinc-binding proteins that by
      activating zinc metalloenzymes participate in the regulation of growth and
      development. The present study was designed to examine the roles of MTs in cell
      proliferation using an in vivo model of liver regeneration following partial
      hepatectomy (PH) in rats. The levels of MT-I and MT-II were studied with respect
      to regulation of proliferative potential, cell cycle checkpoint activity, and
      oxidative stress in the rat PH model. We synthesized a 17-mer antisense
      phosphorothioate oligodeoxynucleotide (S-ODN), named aMT, complimentary to the
      start site of the MT-I mRNA sequence and an appropriate control. Both S-ODNs were
      administered intraperitoneally at the dose of 5 mg/kg following 70% PH. MT became
      induced 57.4 +/- 9.8-fold following PH and the said effect became attenuated
      dramatically following administration of aMT. In addition, PH rats treated with
      aMT exhibited decreased rate of liver regeneration as measured by expression of
      proliferating cell nuclear antigen and elevated cell cycle checkpoint activity as
      determined by expression of p53. The results of these studies suggest that MT
      isoforms with their high thiol contents do play an important role in cellular
      functions and especially during stressful states induced by a broad range of
      mediators generating free radicals.

PMID- 9618278
TI  - Cathepsin D is a good candidate for the specific release of a stable hemorphin
      from hemoglobin in vivo: VV-hemorphin-7.
AB  - Hemorphin peptides, issued from hemoglobin, are emerging as endogenous bioactive
      peptides derived from in vivo tissular degradation of hemoglobin. In order to
      find the enzymes which could be implicated in the in vivo release of these
      peptides, the major lysosomal enzyme cathepsin D was selected, and a study of its
      activity towards hemoglobin and hemorphins was performed. In this paper, it is
      shown that according to the primary specificity of cathepsin D towards
      hemoglobin, this enzyme could constitute a good candidate for the in vivo release
      of two hemorphins: LVV-hemorphin-7 and VV-hemorphin-7. Moreover, these products,
      especially VV-hemorphin-7, are resistant to an extended cleavage by the enzyme.
      Although LVV-hemorphin-7 exhibits a lower resistance, an extended incubation with
      cathepsin D led to the release of the stable peptide VV-hemorphin-7.

PMID- 9618279
TI  - An intestinal bacterial metabolite of ginseng protopanaxadiol saponins has the
      ability to induce apoptosis in tumor cells.
AB  - Our previous study demonstrated that the in vivo anti-metastatic effect induced
      by oral administration of ginseng protopanaxadiol saponins was mediated by their
      metabolic component M1, and that the growth, invasion and migration of tumor
      cells were inhibited by M1 but not by ginsenosides. Here we investigated the
      inhibitory mechanism of M1 on the growth of tumor cells. M1 inhibited the
      proliferation of B16-BL6 mouse melanoma cells in a time- and dose-dependent
      manner, with accompanying morphological changes at the concentration of 20
      microM. In addition, at 40 microM M1 induced apoptotic cell death within 24 h.
      Fluorescence microscopy revealed that dansyl M1 entered the cytosol and quickly
      reached the nuclei (approximately 15 min). Western blot analysis revealed that M1
      rapidly up-regulated the expression of p27Kip1, but down-regulated the expression
      of c-Myc and cyclin D1 in a time-dependent manner. Thus, the regulation of
      apoptosis-related proteins by M1 is responsible for the induction of apoptotic
      cell death, and this probably leads to the anti-metastatic activity in vivo.

PMID- 9618280
TI  - Contribution of CD14 to endotoxin-induced liver injury may depend on types of
      macrophage activation in rats.
AB  - Activated Kupffer cells and hepatic macrophages can produce massive liver
      necrosis through microcirculatory disturbance due to sinusoidal fibrin
      deposition. This mechanism is involved in the development of liver injury after
      endotoxin administration in rats pretreated with heat-killed Propionibacterium
      acnes (P.acnes) or undergoing 70% liver resection. The significance of CD14, a
      receptor for lipopolysaccharide and its binding protein, was evaluated in both
      models in relation to the activation mechanisms of Kupffer cells and hepatic
      macrophages. Northern blot analysis revealed that CD14 mRNA expression was
      increased in the liver of rats following P.acnes administration. In these rats,
      hepatic macrophages immediately after isolation showed marked increased of CD14
      mRNA expression compared to Kupffer cells from normal rats. In contrast, CD14
      mRNA expression was minimal in partially resected liver. Interleukin (IL)-18 and
      IL-2 mRNA expression in the liver and interferon (IFN)-gamma mRNA expression in
      the spleen were significantly increased in P.acnes-treated rats compared to
      normal rats, while these increases were absent in partially hepatectomized rats.
      Thus, CD14 expressed on hepatic macrophages after activation through a cytokine
      network of IL-18, IFN-gamma, and IL-2 may contribute to endotoxin-induced liver
      injury in P.acnes-treated rats. In contrast, in partially hepatectomized rats,
      this network may not operate during Kupffer cell activation, and the liver injury
      might develop through endotoxin receptors other than CD14 on the cells.

PMID- 9618281
TI  - Organization of the human natriuretic peptide receptor A gene.
AB  - We have determined the structural organization of the human natriuretic peptide
      receptor A (hNPRA) gene without screening the genomic library. Based on the
      information for the cDNA of hNPRA, we amplified some fragments of the long
      polymerase chain reaction (PCR) products covering all genomic sequences of the
      gene and directly sequenced the products after extraction and purification. The
      hNPRA gene spans approximately 16 kb and contains 22 exons and 21 introns. All of
      the exon-intron junction sequences coincide with the GT/AG consensus sequence.
      The sequence encoding the transmembrane domain, one part of the hNPRA topological
      structure, exists in exon 7. The results of this first study, determination of
      the hNPRA gene structure, will facilitate further genetic analysis of the hNPRA
      gene and its related diseases.

PMID- 9618282
TI  - New paramagnetic species formed at the expense of the transient tyrosyl radical
      in mutant protein R2 F208Y of Escherichia coli ribonucleotide reductase.
AB  - The highly conserved residue F208 in protein R2 of E. coli ribonucleotide
      reductase is close to the binuclear iron center, and found to be involved in
      stabilizing the tyrosyl radical Y122. in wild type R2. Upon the reconstitution
      reaction of the mutant R2 F208Y with ferrous iron and molecular oxygen, we
      observed a new EPR singlet signal (g = 2.003) formed concomitantly with decay of
      the transient tyrosyl radical Y122. (g = 2.005). This new paramagnetic species
      (denoted Z) was stable for weeks at 4 degrees C and visible by EPR only below 50
      K. The EPR singlet could not be saturated by available microwave power,
      suggesting that Z may be a mainly metal centered species. The maximum amount of
      the compound Z in the protein purified from cells grown in rich medium was about
      0.18 unpaired spin/R2. An identical EPR signal of Z was found also in the double
      mutant R2 F208Y/Y122F. In the presence of high concentration of sodium ascorbate,
      the amounts of both the transient Y122. and the new species Z increased
      considerably in the reconstitution reaction. The results suggest that Z is most
      likely an oxo-ferryl species possibly in equilibrium with a Y208 ligand radical.

PMID- 9618283
TI  - Boron modulates extracellular matrix and TNF alpha synthesis in human
      fibroblasts.
AB  - Boric acid was not mitogenic for human fibroblasts and it did not change cell
      viability until 0.5% (w/v). Boric acid treatment affected the metabolism of human
      dermal fibroblasts in culture, decreasing the synthesis of extracellular matrix
      macromolecules such as proteoglycans, collagen, and total proteins. It also
      increased the release of these molecules into the culture medium. The principal
      proteins secreted into the medium after boric acid treatment had molecular masses
      of 90, 70, 58, 49, and 43 kDa and faint bands were detected by electrophoresis
      between 14 and 30 kDa. hsp 70 and TNF alpha were detected among the secreted
      proteins by immunoblotting, and the amount of TNF alpha released was quantified
      by radioimmunoassay. Total mRNA levels were higher after boric acid treatment and
      peaked after 6 h of treatment. TNF alpha mRNA was undetectable in unstimulated
      fibroblasts and two TNF alpha mRNA bands were detected after stimulation:
      immature mRNA (4.8 kb) and mature TNF alpha mRNA (1.9 kb). Thus, the effects of
      boric acid observed in wound repair in vivo may be due to TNF alpha synthesis and
      secretion.

PMID- 9618284
TI  - Leptin receptor signal transduction: OBRa and OBRb of fa type.
AB  - We report herein the characterization of activities of signal transduction for
      three types of leptin receptors (OBRs) from rats, the OBRa, OBRb, and OBRb with
      fa mutation (OBRb-fa), by measurement of the levels of tyrosine phosphorylation
      of STAT3 (signal transducers and activators of transcription 3) and MAPK (mitogen
      activated protein kinase), which are induced by leptin stimulation of CHO cells
      stably expressing the OBR (CHO-OBRb, CHO-OBRa, or CHO-OBRb-fa cells). As the
      result of leptin stimulation, enhanced levels of tyrosine phosphorylation of
      STAT3 and MAPK were detected in CHO-OBRb cells. In CHO-OBRb-fa cells, enhancement
      levels for both were lower than those in CHO-OBRb cells. In CHO-OBRa cells, only
      the phosphorylation of MAPK was detected. These data suggest that these reduced
      signaling activities cause obesity in fa/fa rats and that OBRa, which has been
      generally thought to be inactive at signaling, actually transmits signals through
      the MAPK pathway.

PMID- 9618285
TI  - A protein phosphatase is involved in the inhibition of histone deacetylation by
      sodium butyrate.
AB  - Treatment of cells with sodium butyrate is known to increase histone acetylation
      by inhibiting deacetylases. Here we have observed, in cultured hepatoma cells,
      that the potent serine-threonine phosphatase inhibitors, okadaic acid or
      calyculin A, inhibited phosphatase activity and concomitantly decreased the
      histone acetylation classically maintained by sodium butyrate. These results
      suggest that a protein phosphatase may mediate the sodium butyrate effect on
      deacetylases. Since we have previously found that such a protein would also
      mediate the sodium butyrate effect on gene expression, we propose that a
      phosphatase activity constitutes an early and essential step in the sodium
      butyrate-triggered signalling pathway.

PMID- 9618286
TI  - Sucrase-isomaltase ontogeny: synergism between glucocorticoids and thyroxine
      reflects increased mRNA and no change in cell migration.
AB  - During postnatal maturation of the rat small intestine, glucocorticoid hormones
      (GC) and thyroxine (T4) act synergistically to elicit a precocious increase of
      sucrase activity. The current work shows that the synergistic effect on sucrase
      activity is paralleled by increased steady-state levels of sucrase-isomaltase
      mRNA. The enhancing effects of T4 on dexamethasone (DEX)-induced sucrase activity
      was seen even after prolonged treatment (9 days). Moreover, when the location of
      sucrase-bearing cells was examined after 2 days of hormone treatment, there was
      distinctly stronger immunostaining of sucrase in the presence of T4, and the
      sucrase-bearing cells were located on the lower quarter of the intestinal villi
      regardless of whether the animals received DEX or T4 plus DEX. Thus, despite
      predictions from the literature, there was no evidence for increased migration in
      the presence of T4. Instead, we conclude that the synergism between the two
      hormones is due to greater accumulation of sucrase-isomaltase per epithelial
      cell.

PMID- 9618287
TI  - An in vitro model to study mesenchymal-epithelial transformation.
AB  - Mesenchymal-epithelial transformation (MET) is an important process in the
      embryogenesis of organisms. In an attempt to study the mechanism of MET, we
      present here the identification of a cloned human chondrosarcoma cell line, the
      SW1353, that is capable of converting to cells with an obvious epithelial
      phenotype. The transformation of the fibroblast-like SW1353 cells to epithelial
      cells occurred in a defined culture condition and the transformed cells displayed
      features characteristic expected to be epithelial cells and formed aggregates
      with cobblestone appearances. We also demonstrated that SW1353 cells not only
      secreted hepatic growth factor (HGF)/scatter factor (SF) but also expressed large
      amounts of p140c-met, the receptor tyrosine kinase for HGF/SF. These results
      suggest that mesenchymal cells, like epithelial cells, are able to express c-met
      proto-oncogene product, and the SW1353 cell culture system can provide us with a
      potential avenue to identify genes responsible for MET.

PMID- 9618288
TI  - Up-regulation of integrin alpha 5 expression by combination of substance P and
      insulin-like growth factor-1 in rabbit corneal epithelial cells.
AB  - To clarify the mechanisms by which substance P (SP) and insulin-like growth
      factor-1 (IGF-1) synergistically facilitate corneal epithelial wound healing, we
      tested the hypothesis that the combination promotes cell attachment to a
      fibronectin matrix through up-regulation of expression of integrin alpha 5 beta
      1, the major cell surface fibronectin receptor in rabbit corneal epithelial
      cells. Cultured rabbit corneal epithelial cells were treated with SP and/or IGF-1
      and then plated on wells coated with fibronectin and bovine serum albumin. After
      incubation, the number of cells attached to the wells was counted. In a second
      experiment, reverse transcription-polymerase chain reaction was used to determine
      the expression of integrin alpha 5 and beta 1 by cells pretreated with SP and/or
      IGF-1. The combination of SP and IGF-1 significantly increased the number of
      cells attached to the fibronectin matrix and the expression of integrin alpha 5.
      However, attachment to the fibronectin matrix was inhibited by the addition of
      GRGDSP, a synthetic peptide that mimics fibronectin. Thus, the synergistic
      enhancing effect of SP and IGF-1 on the attachment of corneal epithelial cells to
      the fibronectin matrix and on corneal epithelial migration is partly due to the
      up-regulation of integrin alpha 5 expression in corneal epithelial cells.

PMID- 9618289
TI  - Plasma heparin-binding EGF-like growth factor levels in patients after partial
      hepatectomy as determined with an enzyme-linked immunosorbent assay.
AB  - We recently showed that heparin-binding EGF-like growth factor (HB-EGF) has
      hepatotrophic effects. In this study, we developed an ELISA system with high
      specificity and sensitivity for human plasma HB-EGF. In 14 patients who underwent
      partial hepatectomy, plasma HB-EGF levels were measured serially after surgery.
      In patients who underwent gross hepatectomy (lobectomy and segmentectomy), plasma
      HB-EGF levels increased, reaching maximal levels approximately 5 to 7 days after
      surgery. In patients who underwent minor hepatectomy (subsegmentectomy), plasma
      HB-EGF levels did not increase. Maximal plasma HB-EGF levels were significantly
      higher in patients who had a percent increased volume of the remaining liver
      (%ILV) above 20% than those who had a %ILV below 20% (32.4 +/- 19.6 pg/ml vs 7.4
      +/- 2.7, P < 0.05). The plasma HB-EGF values did not correlate with WBC counts, C
      reactive protein, or alanine aminotransferase. Plasma HB-EGF may be a marker for
      liver regeneration after hepatectomy in humans.

PMID- 9618290
TI  - Regulation of cellular adhesion to extracellular matrix proteins by galectin-3.
AB  - The control of cellular adhesion to extracellular matrix proteins is poorly
      understood. In the present analyses, we set out to test the hypothesis that high
      galectin-3 concentration on the cell surface downregulates cellular adhesion to
      the extracellular matrix proteins. Various tumor cell lines were briefly
      incubated without or with galectin-3 and then allowed to adhere to wells coated
      with laminin-1, collagen IV and fibronectin. Our data demonstrated that the cells
      which were incubated with galectin-3 prior to plating had significantly reduced
      adhesion to extracellular matrix proteins. This inhibition involved the
      carbohydrate recognition domain of the lectin because adhesion was achieved in
      the presence of galectin-3 and lactose but not galectin-3 and sucrose.
      Furthermore we demonstrated that galectin-3 associates with alpha 1 beta 1
      integrin in a lactose dependent manner.

PMID- 9618291
TI  - Inactivation defects produced by a myopathic II-S6 mutation of the muscle sodium
      channel.
AB  - We have studied the expression in frog oocytes of the alpha-subunit of the rat
      skeletal muscle sodium channel mutation S798F, homologous to the mutation S804F
      of the human isoform, that causes potassium aggravated myotony (PAM), a muscular
      hereditary disease in humans. Wild type channels show a bimodal inactivation,
      with two gating modes that inactivate with time constants that differ at least by
      one order of magnitude and a steady steady-state voltage dependence of the slow
      mode shifted by +27 mV relative to that of the fast mode. In the myopathy-linked
      mutant the propensity of the channel to gate in the slow mode is significantly
      increased and there are alterations in the inactivation properties of both modes.
      The half inactivation potential of the fast mode is shifted negatively, and the
      inactivation kinetics of both modes are slower, with an apparent shift in their
      voltage dependence. The changes on the inactivation properties of the mutant
      channel may be related with the muscle fibre hyperexcitability observed patients
      affected by PAM.

PMID- 9618292
TI  - Expression systems for study of mycobacterial gene regulation and development of
      recombinant BCG vaccines.
AB  - Successful genetic engineering of mycobacteria is crucial for developing new
      approaches to combat tuberculosis as well as for dissecting out the molecular
      basis of pathogenesis of Mycobacterium tuberculosis. We have constructed a
      Mycobacterium-Escherichia coli shuttle expression vector pSD5. It carries a
      modular expression cassette which provides sites for cloning of promoters, a
      ribosome binding site (RBS) with an appropriately placed initiation codon and
      multiple cloning sites for cloning the genes of interest. We also constructed
      pDK20, an integration proficient derivative of pSD5, by incorporating
      mycobacteriophage L5 integration signals in lieu of the origin of DNA replication
      for mycobacteria. This vector permits stable expression of genes in M.bovis BCG,
      M.smegmatis, and M.tuberculosis under the transcriptional control of a
      mycobacterial promoter. These vectors enable the expression of a gene to be
      regulated by several hundred fold depending upon the strength of mycobacterial
      promoter. We propose that expression of protective antigens using an appropriate
      promoter derivative of pDK20 should help in development of recombinant BCG
      vaccines that can induce an optimal immune response from the host. We have
      further employed the integration proficient expression system for comparing the
      efficiency and specificity of transcriptional recognition in M.bovis BCG,
      M.tuberculosis, and M.smegmatis. We show that fast growing M.smegmatis and slow
      growing M.tuberculosis and M.bovis BCG recognize mycobacterial promoters with
      comparable efficiency inspite of differences in their growth rates.

PMID- 9618294
TI  - Direct identification of each specific mutation in codon 12 and 13 of ci-ki-ras2
      by SSCP analysis.
AB  - We compared the SSCP behaviour of the DNA fragments containing c-ki-ras 2 wild
      type 12 and 13 codons or each of the 12 possible point mutated sequences in these
      two codons. We found that a single electrophoresis condition was sufficient to
      distinguish each specific mutation from the other 11 and from the wild type
      sequence. This observation makes it possible to identify each specific mutation
      directly by SSCP without any need for reamplification and sequencing.

PMID- 9618293
TI  - Molecular cloning of the gene for the human prostaglandin transporter hPGT: gene
      organization, promoter activity, and chromosomal localization.
AB  - Prostaglandins (PGs) play diverse and important roles in human health and
      disease. We recently identified the first known PG transporter cDNA in the rat
      (PGT) and human (hPGT). To aid in the analysis of any possible human disease
      caused by mutations in PGT, we have cloned and characterized the hPGT gene. The
      gene exists as a single copy in the human genome and is comprised of 14 exons
      distributed over approximately 95 kb. Two introns disrupt putative trans-membrane
      spans of the coding region; each of these sites is near a highly conserved
      charged residue. The approximately 250 bp immediately 5' to the start of exon 1
      contain a TATAAA sequence (TATA box), a transcription initiation (Inr) consensus
      (CTCANTCT), two Sp 1 sequences (GGGCGG), and a cAMP response element (CGGCGTCA).
      Ligation of approximately 3.5 kb of 5' flanking sequence to a luciferase reporter
      yielded > 15-fold activity above background when expressed in A549 human lung
      epithelial cells. PCR-based monochromosomal somatic cell hybrid mapping and
      fluorescence in situ hybridization localized hPGT to chromosome 3q21. Three
      microsatellites were identified, one of which was demonstrated to be polymorphic
      in unrelated individuals and may be useful in evaluating PGT as a candidate gene
      in human disease.

PMID- 9618295
TI  - Activation of JNK in the remote myocardium after large myocardial infarction in
      rats.
AB  - A large myocardial infarction (MI) causes a chronic hemodynamic load on the
      uninjured remote myocardium (RM). This may lead to oxidative stress, activation
      of stress-induced cell signaling and increase in myocyte apoptosis. MI was
      produced in 6 rats (INF) while 4 rats underwent sham operation (CON). At four
      weeks, there was 128% increase in right ventricular hypertrophy in the hearts
      from INF vs. CON. Western blot analysis showed 3.8 fold increase in JNK
      phosphorylation within the RM from INF vs. CON, confirmed by a 4.2 fold increase
      in JNK kinase activity. There was a 52% increase in TBARS within the RM from INF
      vs. CON, suggesting increased lipid peroxidation. Furthermore, there was a
      twofold increase in myocyte apoptosis within the RM in INF vs. CON. We conclude
      that the RM from INF is associated with activation of JNK, increased oxidative
      stress and enhanced myocyte apoptosis.

PMID- 9618296
TI  - Hepatocyte growth factor protects renal epithelial cells from apoptotic cell
      death.
AB  - Hepatocyte growth factor (HGF) is a pleiotropic factor that plays an essential
      role in renal tubular repair and regeneration following injury. Studies indicate
      that administration of exogenous HGF to animals stimulates renal epithelial cell
      DNA synthesis and accelerates recovery from acute renal failure (ARF). However,
      whether increased cell proliferation accounts for all of the beneficial effects
      of HGF in ARF is unknown. In this study, we demonstrate that HGF protects renal
      epithelial cells from undergoing apoptotic cell death. Treatment of renal
      epithelial mIMCD-3 cells with 25 microM cisplatin in the serum-free medium
      induced significant apoptosis, as assessed by fluorescent Dye H-33342 staining,
      TUNEL staining, light and electron microscopy, and DNA laddering analysis.
      However, constitutive expression of HGF by transfection in mIMCD-3 cells resulted
      in resistance to cisplatin-induced apoptotic death. The survival rate of HGF
      producing C1 cells was more than 2-fold greater as compared to control, mIMCD-3
      cells following treatment with 25 microM cisplatin for 2 days. These results
      suggest that HGF may not only activate tubular repair processes but also
      ameliorate the initial injury by protecting renal epithelial cells from
      undergoing apoptosis.

PMID- 9618297
TI  - Selectivity of sphingosine-induced apoptosis. Lack of activity of DL-erythyro
      dihydrosphingosine.
AB  - Sphingosine (Sph) is emerging as an intracellular regulator of cellular
      differentiation and apoptosis (Ohta, et al., Cancer Res., 55, 691-697, 1995). We
      have recently found that both Sph and its methylated derivative N,N
      dimethylsphingosine (DMS) inhibit mitogen-activated protein kinase (MAPK)
      activity, suggesting that Sph-induced apoptosis may be mediated at least partly
      through inhibition of MAPK (Sakakura, et al., Int J Oncol, 11, 31-39, 1997). We
      report in this study that three stereoisomers, D-erythro-Sph, L-threo-Sph, and DL
      erythro-dihydrosphingosine, were tested in induction of apoptosis and inhibition
      of MAPK activity in three different kinds of solid tumor cell lines. D-erythro
      Sph was strongest in these effects among three compounds. L-threo-Sphingosine was
      partly active. On the other hand, DL-erythro-dihydrosphingosine was totally
      inactive. These results demonstrate the specificity of sphingosine action in
      induction of apoptosis and inhibition of MAPK, suggesting that Sph may play an
      important role as a physiological intracellular messenger of apoptosis in these
      cancer cells.

PMID- 9618298
TI  - Identification of cGMP-dependent protein kinase anchoring proteins (GKAPs).
AB  - To promote both efficiency and selectivity, many protein kinases and phosphatases
      are maintained in specific subcellular microenvironments through their
      association with anchoring proteins. In this study, we describe a new class of
      proteins, called GKAPS, that specifically bind the Type II cGMP-dependent protein
      kinase (PKG). GKAPs were detected in rat aorta, brain, and intestine using a
      protein overlay technique. The PKG binding proteins were distinct from AKAPs,
      proteins known to bind the cAMP-dependent protein kinase (PKA). Furthermore, a
      synthetic peptide that blocks association of PKA with AKAPs did not affect the
      PKG-GKAP interaction. Deletion mutagenesis was used to map the GKAP binding
      determinants within PKG to the N-terminal regulatory region. While most GKAPs
      were tissue-specific, a ubiquitous PKG-binding protein was detected and
      identified as myosin. Analysis of myosin fragments revealed that PKG binds within
      Subfragment 2. The results define a novel class of anchoring proteins that may
      target PKG for specific functional roles.

PMID- 9618299
TI  - In vivo heat shock protects rat myocardial mitochondria.
AB  - Heat shock (HS)/stress proteins (HSP) provide protection from a variety of
      stresses other than HS, including oxidative stress and mitochondria have been
      implicated as the target of HS-related protection in stressed cultured cells.
      Here we investigated whether mitochondria also are targets for the HS-mediated
      protection in vivo. Sprague Dawley rats were exposed, or not, to HS (41 degrees
      C, 15 min). After a 21 h recovery period, hearts were excised and perfused with
      or without H2O2 (0.15 mM). Myocardial mitochondria were then isolated, and their
      oxygen consumption was analyzed. HS prevented H2O2-induced alterations in state 3
      respiration while increasing the expression of Hsp70 and heme oxygenase (HO).
      Thus, in vivo HS protects rat myocardial mitochondrial respiration against the
      deleterious effects of oxidative injury, a protection relating to Hsp70 and/or HO
      and targeting state 3 respiration.

PMID- 9618300
TI  - CD63, a member of tetraspan transmembrane protein family, induces cellular
      spreading by reaction with monoclonal antibody on substrata.
AB  - In our previous paper, we reported that a monoclonal antibody (MAb) 710F, which
      recognizes a cell surface glycoprotein, induces morphological change in monocytic
      cells, promoting cellular adhesion and extensive spreading on tissue culture
      dishes [Koyama et al., Biochem, Biophys. Res. Commun., 168 (1990) 898-904]. We
      report here that the antigen was identified to be CD63, a member of tetraspan
      transmembrane protein family, by purification of the antigen molecule and
      subsequent cDNA cloning. The identity was further evidenced by sequential
      immunoprecipitation experiments using MAb 710F and anti-CD63, MAb2.28, and by
      their reactions with insect cells infected with baculovirus carrying CD63
      expression cassette. Furthermore, the MAb2.28 exhibited cell-spreading activity,
      although to a lesser extent than MAb710F, suggesting the participation of CD63 in
      adhesion and spreading of monocytic cells.

PMID- 9618301
TI  - How the substitution of K188 of trypsin binding site by aromatic amino acids can
      influence the processing of beta-casein.
AB  - Aspartyl 189 residue of trypsin is known to be essential for specific lysis of
      Arg-X and Lys-X bonds. Undertaking to modulate the catalytic properties of this
      protease, otherwise highly conserved K188 was replaced with aromatic amino acid
      residues aiming the perturbation of the electrostatics and the amplifying of
      hydrophobic interactions of the substrate binding site. The catalytic properties
      of the mutants K188F, K188Y, and K188W were measured at pH 7, 8, 9, and 10 using
      a pair of synthetic tetrapeptide p-nitroanilide substrates and beta-casein. The
      kinetic analysis reveals that all the mutants conserve the native trypsin
      capacity to split peptide bonds containing arginyl and lysyl residues.
      Surprisingly, however, depending on mutation, the optimum pH of activity changes.
      As demonstrated only by proteolysis of a natural substrate, all mutants cleave
      also peptide bonds involving asparagine and glutamine. These stuttered cleavage
      sites are close to the beta-casein fragments in beta-sheet according to
      Hydrophobic Cluster Analysis.

PMID- 9618302
TI  - Leptin gene transfer into muscle increases lipolysis and oxygen consumption in
      white fat tissue in ob/ob mice.
AB  - The effects of leptin production in ob/ob mice injected with a plasmid expression
      vector containing mouse leptin cDNA in the tibialis anterior muscle were
      investigated. A significant reduction in food intake (-18%, p < 0.01) along the
      experimental period was found after DNA injection, while differences in body
      weight gain were only significant (-41%, p < 0.05) when determined between days
      2.9 of the study. Concerning adipocytes metabolism, there was a significant
      increase in oxygen consumption in vitro (+34%, p < 0.05) and in basal lipolysis
      (+151%, p < 0.05) in DNA-injected mice compared to PBS-injected animals. Our
      results confirm that functional leptin can be produced in muscle and released
      into the blood stream and give new support to the fact that leptin may have
      direct auto- or paracrine effects on adipocytes, possible contributing to the
      weight- and fat-reducing effects of leptin in ob/ob mice.

PMID- 9618303
TI  - Involvement of reactive oxygen intermediates in lectin-induced protein-tyrosine
      phosphorylation of Syk in THP-1 cells.
AB  - Oxidative stress (H2O2) has been shown to be associated with tyrosine
      phosphorylation and activation of protein-tyrosine kinase Syk. In the present
      study, we examined the possibility that reactive oxygen intermediates (ROI) were
      involved in concanavalin A (Con A)-induced tyrosine phosphorylation in THP-1
      cells. Rapid tyrosine phosphorylations of Syk, Fc gamma receptor(s) and
      phospholipase C gamma 2 (PLC gamma 2) were induced by Con A treatment in THP-1
      cells. Pretreatment of cells with antioxidants N-acetylcysteine (NAC) and
      glutathione (GSH) almost completely blocked tyrosine phosphorylations of Syk, Fc
      gamma receptor(s) and PLC gamma 2. In addition, THP-1 cells showed significant
      levels of ROI from the early period of Con A treatment and the levels of ROI were
      inhibited by antioxidant treatment. These data suggest that ROI have an important
      role in Con A-induced protein-tyrosine kinase(s) signaling pathways.

PMID- 9618304
TI  - Generation of recombinant adenovirus vector with infectious adenoviral genome
      released from cosmid-based vector by simple procedure allowing complex
      manipulation.
AB  - To perform the complex manipulation of the adenoviral genome for the construction
      of recombinant adenovirus vectors, we developed a cosmid vector (pacad1A) from
      which an infectious E1 and E3-deleted adenoviral genome can be released with PacI
      digestion. The cosmid vector, pacad1A, has unique restriction enzyme sites that
      are created for the insertion of foreign genes into the deleted E1 or E3 region
      of the adenoviral genome. To demonstrate the feasibility of the construction of
      adenovirus vectors with our developed vector, we showed that a recombinant
      adenovirus bearing a self-contained tetracycline-regulated expression system
      could be generated by transfection of cells with an infectious adenoviral genome
      that was released from pacad1A-derived plasmid DNA. The recombinant adenovirus
      vector was obtained easily by this method, and the expression of a transgene was
      proved to be regulated with tetracycline in CHO-K1 cells.

PMID- 9618306
TI  - Identification of a novel gene--SSK1--in human endothelial cells exposed to shear
      stress.
AB  - To identify transcriptionally regulated genes potentially involved in the effect
      of shear stress on endothelial gene expression, we performed a differential
      display analysis of mRNAs from human umbilical vein endothelial cell (HUVEC)
      exposed to laminar shear stress (12 dynes/cm2) in comparison to HUVEC maintained
      in static condition. We identified a cDNA fragment overexpressed by laminar shear
      stress. The full-length, SSK1, was 3653 long and encoded for a novel protein of
      1050 amino acids. Northern blot demonstrates that SSK1 mRNA is expressed at high
      levels also in placenta, a weak transcript was present in heart, skeletal muscle,
      kidney and pancreas. Homology searches of the protein databases showed that SSK1
      is related to numerous serine-threonine kinases. The highest homology was found
      with a very recently described gene, BUBR1, an analogue of BUB1, which is a
      kinase involved in the regulation of cell cycle. The most conserved residues in
      catalytic domains II, III, VIb, VII, VIII and IX of serine-threonine protein
      kinases were found in the C terminal region of SSK1 which further supports the
      kinase nature of the new protein. The putative serine-threonine kinase SSK1 may
      represent a tool by which mechanical forces regulates phosphorylation events
      within endothelial cells.

PMID- 9618305
TI  - Transforming growth factor-beta 1 stimulates or inhibits cell growth via down- or
      up-regulation of p21/Waf1.
AB  - Transforming growth factor-beta (TGF-beta) regulates cell proliferation
      positively or negatively. The mitoinhibition by TGF-beta has been attributed to
      induction of cyclin-dependent kinase (CDK) inhibitors, such as p15/ Ink4B,
      p27/Kip1, and p21/Waf1 also known as Cip1 and Sdi1. However, the biological
      process by which TGF-beta exerts the stimulatory effects on cell growth remains
      poorly understood. Here we report that TGF-beta 1 stimulates DNA synthesis of IMR
      90 human embryonic lung fibroblasts but inhibits that of HuCCT1 human
      cholangiocarcinoma cells, via down- or up-regulation of p21/Waf1, respectively.
      TGF-beta 1 markedly suppresses IMR-90 cells to express two different kinds of the
      p21/Waf1 gene transcription factors, the p53 tumor suppressor and the interferon
      regulatory factor-1 (IRF-1). This is followed by a marked decrease in expression
      of p21/Waf1 in a manner consistent with the timing of activation of cyclin E
      associated kinase, which normally accompanies the G1-S transition in the cell
      cycle. Contrarily, TGF-beta 1-induced inhibition of DNA synthesis in HuCCT1 cells
      is preceded by IRF-1-dependent but p53-independent up-regulation of p21/Waf1
      expression followed by inactivation of cyclin E-associated kinase. Thus the cell
      growth stimulation or inhibition by TGF-beta 1 are mediated by the down- or up
      regulation of p21/ Waf1, respectively.

PMID- 9618307
TI  - Adenosine receptor mediates motility in human melanoma cells.
AB  - Cell motility is an essential component of tumor progression and metastasis. A
      number of factors, both autocrine and paracrine, have been found to influence
      cell motility. In the present study, adenosine and adenine nucleotides directly
      stimulated chemotaxis of A2058 melanoma cells in the absence of exogenous
      factors. Three adenosine receptor agonists stimulated motility in the melanoma
      cells and two adenosine receptor antagonists strongly inhibited the chemotactic
      response to both adenosine and AMP. The chemotactic stimulation by adenosine and
      AMP was pertussis toxin sensitive. Otherwise unresponsive Chinese hamster ovary
      cells which were transfected with the adenosine A1 receptor cDNA acquired the
      direct, pertussis toxin sensitive, chemotactic response to adenosine, and this
      response was inhibited by adenosine receptor antagonists. These findings
      demonstrate that adenosine and adenine nucleotides are capable of stimulating
      chemotaxis of tumor cells mediated through an adenosine receptor, probably of the
      A1 subtype. The possibility of antimetastatic therapies based on inhibition of
      adenosine receptor activity is raised.

PMID- 9618308
TI  - The spontaneous induction of glutamine synthetase in pig hepatocytes cocultured
      with RL-ET-14 cells is completely inhibited by trijodothyronine and okadaic acid.
AB  - Cocultivation of primary pig hepatocytes with RL-ET-14 cells, an endothelial-like
      cell line resulted in spontaneous induction of glutamine synthetase (GS)-activity
      in the hepatocytes by more than 10-fold within 120 h to 144 h. Hepatocyte
      specific induction was confirmed by immunocytochemistry. Addition of
      trijodothyronine (T3) to the culture medium inhibited the induction in a
      concentration dependent manner. No comparable influence of T3 was seen with pure
      cultures of either cell type suggesting that only the spontaneous induction was
      affected. Other hormones such as glucagon, insulin, growth hormone, epinephrine
      and testosterone did not interfere with the induction. Addition of several
      protein kinase-inhibitors such as staurosporine and genistein were without
      influence. However, a strong inhibition was found after addition of okadaic acid
      in nanomolar concentrations indicating an involvement of protein-phosphatase 2A
      in the induction process.

PMID- 9618309
TI  - Differential regulation of uncoupling proteins by chronic treatments with beta 3
      adrenergic agonist BRL 35135 and metformin in obese fa/fa Zucker rats.
AB  - The expressions of uncoupling proteins 2 and 3 (UCP2; UCP3) mRNA were studied in
      obese (fa/fa) Zucker rats treated with two weight gain reducing agents for three
      weeks. The specific beta 3-adrenoceptor agonist BRL 35135 (0.5 mg/kg/day orally)
      increased the expression of UCP3 mRNA by 3.8-fold (P < 0.0001; two-way ANOVA) and
      that of UCP1 mRNA by 2.6-fold (P = 0.014) in brown adipose tissue, but had no
      effect on expression of UCP3 mRNA in white fat or in the soleus muscle, or on
      UCP2 mRNA expression in brown or white fat. The antihyperglycemic metformin (300
      mg/kg/day orally) had no effect on expressions of UCP1, UCP2 or UCP3 in any
      tissue studied. Concentrations of plasma insulin were significantly correlated
      with the levels of white fat UCP2 mRNA (in the control group: r = 0.89, P =
      0.0015) and UCP3 mRNA (in the control group: r = 0.80, P = 0.009) suggesting that
      insulin may play a role in the control of UCP2 and UCP3 mRNA expressions in white
      adipose tissue.

PMID- 9618311
TI  - Adenovirus vectors as transcomplementing templates for the production of
      replication defective retroviral vectors.
AB  - We have generated an adenovirus containing a retroviral vector sequence encoding
      the neomycin phosphotransferase (neo) gene (AV-LXSN). AV-LXSN transduction of
      retroviral packaging cell lines led to production of LXSN retroviral vector with
      alternative viral envelopes; exposure of target cells to retroviral containing
      supernatants confirmed envelope specific tropism. Retroviral titers (G418 cfu/ml)
      were comparable to those produced by standard techniques. Retrovirus could be
      detected in supernatants within 24 hours of AV-LXSN transduction and persisted as
      long as 120 hours. Southern blot analysis of DNA purified from populations of
      G418 cells showed the presence of a single neo containing restriction fragment of
      the appropriate size that could only be generated by reverse transcription of
      LXSN to produce LXSN provirus. This adeno-retroviral chimeric vector system could
      simplify the generation and testing of different retroviral vectors, particularly
      where assessment of vectors with alternative envelopes carrying novel targeting
      ligands is required.

PMID- 9618310
TI  - Over expression of the murine myotonic dystrophy protein kinase in the mouse
      myogenic C2C12 cell line leads to inhibition of terminal differentiation.
AB  - Myotonic dystrophy (DM) is an autosomal dominant human disorder, caused by the
      abnormal expansion of a CTG trinucleotide repeat in the 3' untranslated region of
      a protein kinase gene (DMPK). Muscle symptoms are a common feature of the
      disorder and in the adult onset cases there are increased patterns of muscle
      fibre degeneration and regeneration. In the congenitally affected infants there
      is a failure of muscle maturation, with the histological presence of numerous
      immature fibres. However, the pathological mechanism in both forms of the disease
      is unclear. We report that over-expression of the murine dmpk gene, in a murine
      myogenic cell line, leads to markedly reduced levels of fusion to the terminally
      differentiated state. These findings complement recently published data using a
      heterologous expression/cell system and may have implications for the
      understanding of the disease process in this disorder.

PMID- 9618317
TI  - How Do you read RTP? 
AB  - Copyright

PMID- 9618312
TI  - Tightly regulated expression of the entire hepatitis C virus structural region in
      continuous human cell lines.
AB  - Investigation of the hepatitis C virus (HCV) life cycle is limited by the lack of
      an efficient cell culture system. Employing a tetracycline-regulated gene
      expression system we generated a panel of continuous human cell lines allowing
      the inducible expression and faithful processing of HCV structural proteins as
      well as of a functional NS2-3 autoprotease. HCV proteins were found in the
      cytoplasm in a pattern characteristic for the endoplasmic reticulum. High-level
      expression of HCV proteins was found to be cytotoxic. These cell lines represent
      a unique in vitro system in which to further investigate the structural proteins
      of HCV and to evaluate novel antiviral strategies against hepatitis C in a well
      defined and reproducible cellular context.

PMID- 9618318
TI  - Follow-Up to the study: A randomized, double-blind, placebo-controlled consumer
      rechallenge test of olean salted snacks 
AB  - Copyright

PMID- 9618319
TI  - Human variability and noncancer risk assessment- An analysis of the default
      uncertainty factor 
AB  - A 10-fold uncertainty factor is used for noncancer risk assessments to allow for
      possible interindividual differences between humans in the fate of the chemical
      in the body (kinetics) and target organ sensitivity (dynamics). Analysis of a
      database on the variability in each of these aspects is consistent with an even
      subdivision of the 10-fold factor into 10(0.5) (3.16) for kinetics and 10(0.5)
      (3.16) for dynamics. Analysis of the number of subjects in a normally and log
      normally distributed population which would not be covered by factors of 3.16
      supports this subdivision and also the use of a 10-fold factor to allow for both
      aspects. Analysis of kinetic data for subgroups of the population indicates that
      the standard default value of 3.16 for kinetics will not be adequate for all
      routes of elimination and all groups of the population. A scheme is proposed
      which would allow the selection of appropriate default uncertainty factors based
      on knowledge of the biological fate and effects of the chemical under review.
      Copyright 1998 Academic Press.

PMID- 9618320
TI  - Toxicological risk assessment in the courtroom: are available methodologies
      suitable for evaluating toxic tort and product liability claims? 
AB  - Courts are increasingly faced with the need to resolve claims by individuals that
      they have been injured by chemical exposures or that they have been put at
      sufficient risk by such exposures that their health status must be monitored to
      ensure the earliest possible detection of developing injuries or diseases. This
      paper offers the view that the principles and methods developed and applied by
      toxicologists, epidemiologists, and risk assessors to support regulatory and
      public health decision-making are inadequate to evaluate the types of claims that
      courts are called upon to resolve in such cases. No well-described alternative
      methodology appears to be available, and as a result, courts are exposed to a
      wide range of expert opinions based on diverse, conflicting, and sometimes
      baseless methodologies. It is suggested that there may be value in an effort by
      the community of professionals in toxicology, epidemiology, and risk assessment
      to devote attention to the types of data and scientific methodologies that might
      be appropriate for evaluating the technical questions that such claims provoke.
      Such an effort might assist trial judges in the role they have been assigned in
      the Supreme Court's 1993 Daubert decision, wherein they are asked to make a
      preliminary assessment of the admissibility of the scientific methodologies
      relied upon by various experts. Such an assessment, if based on an understanding
      of the types of data and methodologies suitable for evaluating claims of injury,
      offers the possibility of limiting the range of expert opinion that ultimately is
      heard in courtrooms to that which conforms to scientifically valid standards.
      Copyright 1998 Academic Press.

PMID- 9618321
TI  - Validating new toxicology tests for regulatory acceptance 
AB  - Before a new or revised toxicology test is considered acceptable for safety
      evaluation of new substances, the test users and the industrial and regulatory
      decision makers must feel comfortable with it, and the decisions it supports.
      Comfort with, and the acceptance of, a new test comes after knowing that it has
      been validated for its proposed use. The validation process is designed to
      determine the operational characteristics of a test, that is, its reliability and
      relevance, in addition to its strengths and limitations. The reliability of a
      test is measured by its reproducibility. Its relevance is judged by its
      mechanistic relationship to the health effects of concern, and its ability to
      predict or identify those effects. The U.S. government has recently formed the
      Interagency Coordinating Committee on the Validation of Alternative Methods
      (ICCVAM) to work with federal agencies and test developers to coordinate the
      evaluation and adoption of new test methods. The ICCVAM will provide guidance to
      agencies and other stakeholders on criteria and processes for development,
      validation, and acceptance of tests; coordinate technical reviews of proposed new
      tests of interagency interest; facilitate information sharing among agencies; and
      serve as an interagency resource and communications link with parties outside of
      the federal government on matters of test method validation. Copyright 1998
      Academic Press.

PMID- 9618322
TI  - Use of EC criteria for determining health and environmental hazards for
      classification of chemicals for environmental risk 
AB  - Copyright

PMID- 9618323
TI  - Do peroxisome proliferating compounds pose a hepatocarcinogenic hazard to humans?
AB  - The purpose of the workshop "Do Peroxisome Proliferating Compounds Pose a
      Hepatocarcinogenic Hazard to Humans?" was to provide a review of the current
      state of the science on the relationship between peroxisome proliferation and
      hepatocarcinogenesis. There has been much debate regarding the mechanism by which
      peroxisome proliferators may induce liver tumors in rats and mice and whether
      these events occur in humans. A primary goal of the workshop was to determine
      where consensus might be reached regarding the interpretation of these data
      relative to the assessment of potential human risks. A core set of biochemical
      and cellular events has been identified in the rodent strains that are
      susceptible to the hepatocarcinogenic effects of peroxisome proliferators,
      including peroxisome proliferation, increases in fatty acyl-CoA oxidase levels,
      microsomal fatty acid oxidation, excess production of hydrogen peroxide,
      increases in rates of cell proliferation, and expression and activation of the
      alpha subtype of the peroxisome proliferator-activated receptor (PPAR-alpha).
      Such effects have not been identified clinically in liver biopsies from humans
      exposed to peroxisome proliferators or in in vitro studies with human
      hepatocytes, although PPAR-alpha is expressed at a very low level in human liver.
      Consensus was reached regarding the significant intermediary roles of cell
      proliferation and PPAR-alpha receptor expression and activation in tumor
      formation. Information considered necessary for characterizing a compound as a
      peroxisome proliferating hepatocarcinogen include hepatomegaly, enhanced cell
      proliferation, and an increase in hepatic acyl-CoA oxidase and/or palmitoyl-CoA
      oxidation levels. Given the lack of genotoxic potential of most peroxisome
      proliferating agents, and since humans appear likely to be refractive or
      insensitive to the tumorigenic response, risk assessments based on tumor data may
      not be appropriate. However, nontumor data on intermediate endpoints would
      provide appropriate toxicological endpoints to determine a point of departure
      such as the LED10 or NOAEL which would be the basis for a margin-of-exposure
      (MOE) risk assessment approach. Pertinent factors to be considered in the MOE
      evaluation would include the slope of the dose-response curve at the point of
      departure, the background exposure levels, and variability in the human response.
      Copyright 1998 Academic Press.

PMID- 9618324
TI  - The evaluation and hazard classification of toxicological information for
      workplace hazardous materials information system material safety data sheets 
AB  - Hazardous materials used occupationally in Canada are subject to the legislated
      requirements of the Workplace Hazardous Materials Information System (WHMIS).
      This paper describes the administrative framework of WHMIS and how toxicological
      data are evaluated to determine if a substance triggers WHMIS classification for
      the toxicological endpoints of acute toxicity, skin irritation, eye irritation,
      corrosion, dermal sensitization, respiratory sensitization, chronic toxicity,
      mutagenicity, teratogenicity/embryotoxicity, and carcinogenicity. Problems
      encountered with the information on material safety data sheets are also
      discussed for each of the toxicological endpoints. Copyright 1998 Academic Press.

PMID- 9618325
TI  - Granulomas in the livers of humans and fischer rats associated with the ingestion
      of mineral hydrocarbons: A comparison 
AB  - Ninety-day feeding studies were conducted in Fischer 344 rats using a series of
      highly refined mineral hydrocarbons which included mineral oils and waxes
      representative of those used in consumer products and food applications. The
      series included materials which had been refined by oleum or hydrogenation. The
      materials tested were representative of the range of carbon chain lengths,
      molecular weights, and viscosities which are currently in use. Findings revealed
      the presence of granulomatous lesions in the liver and histiocytosis in the lymph
      nodes. Some mineral hydrocarbons did not induce any lesions; others induced
      relatively minor effects; and a low melting point wax induced the largest lesions
      in both liver and mesenteric lymph nodes, with inflammation and areas of focal
      necrosis in the livers. The majority of lesions reported were associated with the
      highest dose levels used. These studies are in contrast to studies in Sprague
      Dawley rats in which comparable doses did not induce similar lesions, indicating
      marked strain variability. Lipogranulomas associated with the ingestion of
      mineral oil have been reported in humans. The comparative morphology of the
      lesions seen in the Fischer rat study and those observed in the human are
      discussed and differences are highlighted. The lesions in the human are not
      believed to progress to lesions of clinical significance. The pathogenesis of the
      lesions induced in Fischer rats and in humans is discussed and it is concluded
      that the majority, if not all of the lesions, in the rats are of no significance
      for humans. The possibility that a small proportion of cases of granulomatous
      hepatitis in humans may represent an atypical response to mineral hydrocarbons
      may need further investigation. Copyright 1998 Academic Press.

PMID- 9618327
TI  - An atypical result: noncorrosivity to skin and eye at pH 0.7 
AB  - Copyright

PMID- 9618326
TI  - What's in a name: toxicokinetics, pharmacokinetics, or just kinetics? 
AB  - Copyright

PMID- 9618328
TI  - Volume 26, number 1, part 2 of 2 (1997), in article no. RT971140 "Setting air
      quality standards for carcinogens: An alternative to mathematical quantitative
      risk assessment-discussion Paper," by R. L. Maynard, K. M. Cameron, R. Fielder,
      A. McDonald, and A. Wadge, pages S60-S770: 
AB  - Copyright

PMID- 9618329
TI  - A multigeneration study to ascertain the toxicological effects of Great Lakes
      salmon fed to rats: study overview and design.
AB  - Fish from the Great Lakes can be contaminated with a plethora of industrial,
      agricultural, and environmental chemicals. These chemicals have been associated
      with reproductive and other toxicological effects in fish and fish-eating birds
      found in the Great Lakes basin. To obtain more insight into this association,
      several laboratory studies have been undertaken wherein fish have been
      incorporated into the experimental diets to determine the effect of their
      ingestion upon the test animals. In addition, several human epidemiological
      studies have found correlations between Great Lakes fish consumption and effects
      in neonates which have been attributed to polychlorinated biphenyls without any
      appreciable consideration as to what synergistic or antagonistic effects other
      chemicals or heavy metals may or may not have contributed to the observed
      findings. Herein is presented the design of a two-generation feeding-reproduction
      study that incorporated lyophilized chinook salmon (Oncorhynchus tsawytscha)
      fillets into the diets of Sprague-Dawley rats. The findings of this study will be
      presented in the sections which follow.

PMID- 9618330
TI  - Dietary and tissue residue analysis and contaminant intake estimations in rats
      consuming diets composed of Great Lakes salmon: a multigeneration study.
AB  - To further characterize the toxicological risk associated with chemical
      contaminants in Great Lakes fish, a multigeneration rat reproduction study was
      designed. Mature chinook salmon (Oncorhynchus tsawytscha), collected during the
      Fall 1991 spawning runs from Sydenham River, Lake Huron, and Credit River, Lake
      Ontario, were filleted, lyophilized, and incorporated into standard rat diets at
      25% (w/w) or 100% (w/w) of the normal protein compliment [casein, 20% (w/w)].
      This resulted in diets composed of 5 or 20% (w/w) lyophilized fish and estimated
      daily fish intakes by the rats at levels approximately 15- and 60-fold greater,
      respectively, than the current estimate for the Canadian public for all fish and
      seafood. Both fresh and lyophilized fish were analyzed for the following groups
      of contaminants: halogenated aromatic hydrocarbons [polychlorinated biphenyls,
      dibenzodioxins, and dibenzofurans (PCBs, PCDDs, PCDFs)], polycyclic aromatic
      hydrocarbons (PAHs), organochlorine pesticides, metals, volatile organics, and
      other extractable organics (chlorinated phenols and benzenes). In general, only
      minor site differences existed for the specific types of contaminants detected;
      however, fish from the Credit River contained slightly greater amounts of PCBs (2
      to 3-fold), dioxin toxic equivalencies (TCDD TEQs; 1.5- to 2.0-fold), DDT and
      metabolites (1. 5-fold), and appreciably higher amounts of mirex (15-fold). This
      general pattern of contaminant differences continued when the various diets were
      prepared using the lyophilized fish. Tissue samples (adipose, liver) were taken
      from the animals at various stages of the study and also analyzed for the same
      groups of contaminants. In general, adipose tissue was the major reservoir for
      organochlorine (OC) pesticides and PCBs, while "dioxin-like" PCDD/DF congeners
      and mercury were found preferentially in the liver. Contaminant intake
      calculations and tissue residue levels are provided.

PMID- 9618331
TI  - The toxicological effects following the ingestion of chinook salmon from the
      Great Lakes by Sprague-Dawley rats during a two-generation feeding-reproduction
      study.
AB  - A two-generation reproduction-feeding study was undertaken with Sprague-Dawley
      rats to ascertain the effects of ingesting chinook salmon fillets caught in the
      Credit River, which empties into Lake Ontario (LO), or in the Owen Sound region
      of Lake Huron (LH). Rats (30/sex/group) were randomly assigned to groups whose
      dietary protein consisted of casein and/or lyophilized salmon [Group 1: 20%
      casein (controls); Group 2: 15% casein + 5% LO salmon (LO-5%); Group 3: 20% LO
      salmon (LO-20%); Group 4: 15% casein + 5% LH salmon (LH-5%); Group 5: 20% LH
      salmon (LH-20%)]. After 70 days on test, the males and females were mated on a
      1:1 basis within diet groups. Approximately 70 days postweaning, one F1 male and
      one F1 female from 24 litters were mated within diet groups, avoiding sibling
      matings. At weaning, the F0 and F1 adults and the F1 and F2 neonates not randomly
      selected for further testing were necropsied. Evaluated parameters included
      growth, feed consumption, organ weights, reproduction indices, serum chemistry,
      hematology, and coagulation times. The only statistically significant effects
      which were present in both generations were increased relative liver and kidney
      weights of both sexes in the LO-20% and LH-20% groups; the LH-20% females had
      lower alanine transaminase activity than the controls; the controls had lower
      creatinine levels than the fish groups and the LO-20% females; the LH-20% and LO
      20% males had a lower blood urea nitrogen than the controls; and the LH-20%
      females had a heavier terminal body weight than the controls and a lower number
      of red blood cells, hematocrit, hemoglobin values, and mean platelet volume.
      There was a tendency for the fish-fed groups to grow faster, eat more feed, and
      have larger litters with heavier pups. Overall, there was little to suggest that
      the myriad of contaminants in chinook salmon from the Great Lakes presented an
      appreciable toxicological risk to Sprague-Dawley growth and reproduction.

PMID- 9618332
TI  - Effects of Great Lakes fish consumption on the immune system of Sprague-Dawley
      rats investigated during a two-generation reproductive study.
AB  - The effects of Great Lakes fish on food consumption, body and organ weights, and
      hematological parameters were investigated in the first- (F1) and second- (F2)
      generation Sprague-Dawley rats assigned to immunological studies. The parent-
      (F0) generation rats were fed either a control diet or diets containing 5 or 20%
      lyophilized chinook salmon from Credit River (Lake Ontario, LO) or Owen Sound
      (Lake Huron, LH). The F1 and F2 pups were exposed to the fish diet in utero,
      through the dam's milk to 21 days of age and through the respective diets to 13
      weeks of age. The study included an F1-reversibility (F1-R) phase in which rats
      at 13 weeks of exposure to fish or control diets were switched to the control
      diet for 3 months. Statistically significant effects included increased growth
      rates in the F1 male rats fed the LH fish diets compared to those fed the LO fish
      diets; increased liver weights in the F2-generation male rats fed the LH-20% and
      LO-20% diets compared to those fed the 5% fish diets; reduced thymus weights in
      the F1-R female rats fed the LO-20% fish diet compared to those fed the LO-5% or
      LH-20% fish diets and in the F2 male rats fed the LO diets compared to those fed
      the LH diets; increased kidney weights in the F2 male rats fed the LH-20% diet
      compared to those fed the LH-5% or LO-20% diets; reduced but reversible effects
      on red blood cell (RBC), white blood cell (WBC), neutrophil, lymphocyte, and
      monocyte numbers in the F1-generation female rats fed the fish diets; reduced red
      blood cell (RBC), white blood cell (WBC), and lymphocyte numbers in the F2 male
      rats fed the LO diets compared to those fed the LH diets; and reduced WBC and
      lymphocyte numbers in the F2 female rats fed the LO-20% diet compared to those
      fed the LH-20% fish diet. These results suggested that long-term exposure to
      Great Lakes fish contaminants may have adverse effects on some immune-related
      parameters. The impact of such changes on the functional aspects of the immune
      system of rats and consequently on human health needs to be further investigated.

PMID- 9618333
TI  - Effects of Great Lakes fish consumption on the immune system of Sprague-Dawley
      rats investigated during a two-generation reproductive study.
AB  - The effects of Great Lakes fish contaminants on several quantitative and
      functional aspects of the immune system were investigated in the first (F1) and
      second (F2) generations of Sprague-Dawley rats. The F0 rats were fed either a
      control diet or diets containing 5 or 20% lyophilized chinook salmon from the
      Credit River of Lake Ontario (LO) and Owen Sound point of Lake Huron (LH). The F1
      and F2 pups were exposed to fish in utero, through the dam's milk to 21 days old,
      and through the dam's respective diets to 13 weeks of age. The study included an
      F1-reversibility (F1-R) phase in which rats at 13 weeks of exposure to fish or
      control diets were switched to the control diet for 3 months. The most
      outstanding finding was a statistically significant increase in absolute spleen
      leukocytes and absolute and percentage lymphocytes in the F2 male rats fed the LH
      fish diets compared to the control and to those fed the LO fish diets with the
      20% fish diets having higher cell numbers compared to the LO-5% fish diets. A
      parallel increase in the T-helper/inducer T-lymphocyte subset numbers was
      observed. Increased but statistically insignificant plaque-forming cell (PFC)
      numbers were obtained in the F2 male rats fed the LH fish diets compared to those
      fed the LO fish diets and in the F1-R female group of rats fed the LH fish diet
      compared to those fed the LO fish diets. Phagocytosis by resident peritoneal
      macrophages was significantly increased in the F1 male and F2 female rats fed the
      fish diets compared to the control. The phagocytic activity was significantly
      higher in the F2-generation male and female rats fed the LO diets compared to
      those fed the LH diets. Other parameters including lymphocyte transformation in
      response to mitogens, the number of Listeria monocytogenes bacteria surviving in
      the rat spleens, and the natural killer cell activity were not affected
      significantly by any of the treatments. Overall, the effects of diets containing
      chinook salmon from the LO and LH sources on the immune system of rats were
      minimal and were on quantitative rather than on functional aspects of the system.
      Further focused research would be required in order to establish conclusively
      that the immune system of cohorts who ingest Great Lakes fish frequently is at a
      greater risk for adverse effects.

PMID- 9618334
TI  - Neurobehavioral effects of chronic ingestion of Great Lakes chinook salmon.
AB  - Cross-generational chronic feeding of either a 5 or a 20% lyophilized Lake Huron
      (LH) or Lake Ontario (LO) chinook salmon diet to rats caused no observable
      effects on many behavioral dimensions including activity, exploration,
      sensorimotor function, and stereotypy. As assessed by the Morris water maze and
      the radial arm maze, there was no diet-induced impairment of spatial learning or
      long-term memory. There was no evidence that the fish diets caused an exaggerated
      response to food reward reduction as had been observed previously for rats fed
      Oswego area Lake Ontario salmon. Effects of the fish diets with the exception of
      one statistically significant but probably meaningless effect on the Morris water
      maze for females were found only for male rats and only for males who ate the 20%
      diet. F1 male rats were reluctant to traverse a runway for a single pellet
      reward. Performance of the reference/working memory version of the radial arm
      maze was affected for the F1 LO-20 rats and for the F2 LH-20 rats. Until further
      research is conducted it would be unwise to ignore indications that male rats may
      show some effect of chronic consumption of the highest concentration of these
      diets, particularly on tasks that require intact frontocortical dopamine
      function.

PMID- 9618335
TI  - Neurochemical effects of consumption of Great Lakes salmon by rats.
AB  - This study, part of a larger project to determine the health consequences of both
      perinatal and adult exposure to contaminated salmon from the Great Lakes,
      determined the neurochemical effects of exposure of rats to chow adulterated with
      lyophilized salmon fillets. Concentrations of biogenic amines, their metabolites,
      and choline acetyltransferase (ChAT) were determined in the frontal cortex (FC),
      nucleus accumbens, caudate nucleus (CN), hippocampus (HC), and substantia nigra
      (SN) of adult rats who had been exposed, both perinatally and as adults, to
      standard rat chow adulterated with either 5 or 20% (w/w) lyophilized fillets from
      either Lake Huron (LH) or Lake Ontario (LO) salmon. Dopamine (DA) concentrations
      in the FC were significantly decreased following exposure to both 20% fish diets.
      CN DA concentrations were significantly reduced in rats exposed to all diets,
      while SN DA was decreased only in the LO20-fed animals. SN norepinephrine
      concentrations were reduced in all groups except for the LO5-fed rats. 3,4
      Dihydroxyphenylacetic acid (DOPAC) concentrations in the FC were significantly
      increased in the LH20 and LO5 groups, while CN DOPAC concentrations were reduced
      in LH20, LO5, and LO20 animals. 5-Hydroxyindoleacetic acid concentrations were
      reduced in the FC and CN of all animals exposed to diets adulterated with Great
      Lakes salmon. ChAT concentrations were unaffected in rats exposed to any of the
      adulterated diets. The significant reductions in DA, particularly in the FC and
      CN, suggest that either fish-borne contaminants or consumption of fish, per se,
      may affect behaviors that require inhibition of normal responding. We conclude
      that consumption of contaminated fish from the Great Lakes may result in
      sufficient reductions in biogenic amine function to result in significant
      deficits in important behavioral functions in the rat and, by inference, in the
      perinatally exposed human.

PMID- 9618336
TI  - Microsomal enzyme activity, glutathione S-transferase-placental form expression,
      cell proliferation, and vitamin A stores in livers of rats consuming Great Lakes
      salmon.
AB  - Male and female Sprague-Dawley rats were fed diets incorporating lyophilized
      chinook salmon obtained from Lake Ontario and Lake Huron. After 70 days, females
      were bred and the progeny (F1) were reared on the same fish-based diets as the
      adults (F0). After 78-133 days on the diets, males and females of both
      generations were sacrificed and hepatic microsomal enzyme activities determined,
      along with glutathione S-transferase-placental form (GSTP) expression and hepatic
      cellular proliferation. Hepatic P450 enzyme activities (MROD, EROD, PROD, BROD,
      and aminopyrine) were increased significantly by fish diets from both sources.
      Increases in hepatic enzyme activity were greatest for fish caught from Lake
      Ontario and reflected the total levels of organochlorine contaminants in the
      fish. GSTP and cell proliferation rates did not show any diet-related or dose
      related changes. Vitamin A stores were analyzed as the concentration of liver
      retinyl palmitate. In rats receiving the highest TEQ dose (i.e., 20% Lake Ontario
      fish diet), vitamin A stores were significantly lower in F0 adults, F1 weanlings,
      and F1 adult females.

PMID- 9618338
TI  - Membrane Channels.
AB  - Copyright

PMID- 9618339
TI  - Lipidic Cubic Phases: New Matrices for the Three-Dimensional Crystallization of
      Membrane Proteins.
AB  - The major constraint in attaining high resolution structures of membrane proteins
      by X-ray crystallography is the growth of well-ordered three-dimensional
      crystals. To enable such crystallizations, we have used lipidic cubic phases
      consisting of monoglycerides and water. Bacteriorhodopsin and lysozyme, as
      paradigms of membrane and soluble proteins, nucleate and grow to well-ordered
      crystals that diffract X-rays isotropically in all three dimensions to 2.0 A. We
      envisage bacteriorhodopsin to partition into, and diffuse within, the bilayer of
      a lipidic cubic matrix, while the polar lysozyme resides in the aqueous
      compartment thereof. The phenomenology of bicontinuous cubic phases, consisting
      of curved bilayers whose structures follow infinitely periodic minimal surfaces
      (IPMS), is presented. Detailed prescriptions of the preparation of lipidic cubic
      phase matrices are given and their potential for the crystallization of other
      biological macromolecules is discussed. Copyright 1998 Academic Press.

PMID- 9618337
TI  - The health Canada Great Lakes multigeneration study--summary and regulatory
      considerations.
AB  - The Health Canada Multigeneration Study was initiated to determine the
      consequences in rodents consuming diets containing Lake Ontario (LO) or Lake
      Huron (LH) chinook salmon over successive generations. Following lyophilization,
      the contaminant levels in the salmon used in the formulation of the diets for
      this study exceeded a number of tolerances or guidelines established for
      contaminants in commercial fish and seafood products (PCBs, dioxin, mirex,
      chlordanes, mercury). Consumption of the fish diets by rats of two consecutive
      generations resulted in a variety of effects that can be described as adaptive
      responses or of limited biological significance. The two exceptions to this were
      (1) the suggestion of modification of working and reference memory in males of
      the high-dose groups 20% fish diets, which may have been related to decreases
      noted in neurotransmitters in several brain regions in these rats; and (2) an
      effect on thymus weights noted in the high-dose first generation (F1)
      reversibility study animals and an overall effect on T-helper/inducer lymphocyte
      subset numbers in the second generation (F2) male rats fed the LH diets compared
      to the LO diets. Relatively minor effects were observed in the rats consuming the
      5% fish diets from either Great Lakes location (LH-5, LH-5), although their fish
      intake was approximately 16-fold greater on a daily basis than the average angler
      consuming Great Lakes sport fish (compared to a 60-fold greater intake in the 20%
      diet groups: LH-20, LO-20). Based on these study results with rats it would
      appear that for the average consumer of Great Lakes sports fish, the risk
      presented by the complex mixture of contaminants in chinook salmon collected from
      these two locations in the Great Lakes basin could be considered minimal,
      especially if sport fish consumption advisories are followed.

PMID- 9618340
TI  - Recent Advances in the High Resolution Structures of Bacterial Channels:
      Gramicidin A.
AB  - Gramicidin is a polypeptide antibiotic which forms dimeric channels specific for
      the transport of monovalent cations across membranes. It adopts several different
      conformations, most notably double helical (pore) and helical dimer (channels)
      forms, which have very different structural and functional characteristics. This
      review focuses on recent high resolution structure determinations of both the
      pore and channel forms of the molecule by X-ray crystallographic and/or NMR
      spectroscopic techniques. It discusses the structural consequences of binding
      ions and the location of ion binding sites and how the structures are related to
      the conductance properties of the molecule. This relatively simple molecule is
      probably the best characterized ion channel (both structurally and functionally)
      and has, to date, been the principal proving-ground for many of our ideas about
      the molecular nature of ion conduction in membranes. Copyright 1998 Academic
      Press.

PMID- 9618341
TI  - Electron Crystallography of Two-Dimensional Crystals of Membrane Proteins.
AB  - Electron microscopy has become a powerful technique, along with X-ray
      crystallography and nuclear magnetic resonance spectroscopy, to study the three
      dimensional structure of biological molecules. It has evolved into a number of
      methods dealing with a wide range of biological samples, with electron
      crystallography of two-dimensional crystals being so far the only method allowing
      data collection at near-atomic resolution. In this paper, we review the
      methodology of electron crystallography and its application to membrane proteins,
      starting with the pioneering work on bacteriorhodopsin, which led to the first
      visualization of the secondary structure of a membrane protein in 1975. Since
      then, improvements in instrumentation, sample preparation, and data analysis have
      led to atomic models for bacteriorhodopsin and light-harvesting complex II from
      higher plants. The structures of many more membrane proteins have been studied by
      electron crystallography and in this review examples are included where a
      resolution of better than 10 A has been achieved. Indeed, in some of the given
      examples an atomic model can be expected in the near future. Finally, a brief
      outlook is given on current and future developments of electron crystallographic
      methods. Copyright 1998 Academic Press.

PMID- 9618342
TI  - Mass Measurement in the Scanning Transmission Electron Microscope: A Powerful
      Tool for Studying Membrane Proteins.
AB  - The technique of mass measurement in the scanning transmission electron
      microscope is briefly presented. Results obtained for membrane proteins, with
      particular emphasis on the channel forming proteins, are discussed. The data
      illustrate the versatility of the technique which is applicable to particulate,
      filamentous, and sheet-like structures. When combined with composition analysis,
      the absolute mass values measured with the STEM allow protein stoichiometries to
      be unambiguously defined. Copyright 1998 Academic Press.

PMID- 9618343
TI  - Exposures from indoor spraying of chlorpyrifos pose greater health risks to
      children than currently estimated.
AB  - Recent findings of indoor exposure studies of chlorpyrifos indicate that young
      children are at higher risks to the semivolatile pesticide than had been
      previously estimated [Gurunathan et al., Environ Health Perspect 106:9-16
      (1998)]. The study showed that after a single broadcast use of the pesticide by
      certified applicators in apartment rooms, chlorpyrifos continued to accumulate on
      children's toys and hard surfaces 2 weeks after spraying. Based on the findings
      of this and other research studies, the estimated chlorpyrifos exposure levels
      from indoor spraying for children are approximately 21-119 times above the
      current recommended reference dose of 3 microg/kg/day from all sources. A joint
      agreement reached between the U.S. Environmental Protection Agency and the
      registrants of chlorpyrifos-based products will phase out a number of indoor uses
      of the pesticide, including broadcast spraying and direct uses on pets. While
      crack and crevice treatment of insects (such as cockroaches and termites) by
      chlorpyrifos will still continue, it appears prudent to explore other insect
      control options, including the use of baits, traps, and insect sterilants and
      growth regulators. To ensure global protection, adequate dissemination of
      appropriate safety and regulatory information to developing regions of the world
      is critical, where importation and local production of chlorpyrifos-based
      products for indoor uses may be significant.

PMID- 9618344
TI  - Human exposure and risk from indoor use of chlorpyrifos.
AB  - The toxicity, exposure, and risk from chlorpyrifos are briefly discussed in
      juxtaposition with two recent articles in Environmental Health Perspectives
      concerning potential exposures to children. In studies conducted according to EPA
      guidelines, chlorpyrifos has been shown not to be mutagenic, carcinogenic, or
      teratogenic, nor does it adversely affect reproduction. Chlorpyrifos toxicity
      does not occur in the absence of significant cholinesterase inhibition. If
      exposures are less than those that cause significant cholinesterase depression,
      then no signs or symptoms related to chlorpyrifos exposure occur. The weight of
      empirical evidence indicates that the risk of adults or children experiencing an
      adverse health effect from exposure to chlorpyrifos through both nondietary and
      dietary sources is negligible. Both the research supporting the registration of
      these products and their long history of widespread use suggest that unless these
      products are seriously misused, their margins of safety are wide enough to
      protect everyone with the potential to be exposed. A weight-of-evidence review of
      the entire scientific knowledge base relating to chlorpyrifos products supports
      these conclusions.

PMID- 9618345
TI  - Environmental pollution and child health in central and Eastern Europe.
AB  - For the last 50 years, the economic and industrial development of the nations of
      Central and Eastern Europe has been achieved at the cost of environmental
      degradation. The health risks posed by this pollution to children and the steps
      necessary to ameliorate such risks are only beginning to be investigated. At a
      recent conference in Poland, sponsored in part by the National Institute of
      Environmental Health Sciences, participants from 11 countries in the region,
      together with scientists from Western Europe and the United States, met to share
      information regarding pediatric environmental health in Central and Eastern
      Europe, to consider methodologic issues in the design and conduct of such
      studies, and to discuss preventive strategies. This report summarizes the
      deliberations, outlines problem areas such as heavy metals and air pollution,
      delineates research and training needs to help Central and Eastern Europeans deal
      more effectively with such problems, and recommends specific future actions and
      collaborative efforts.

PMID- 9618346
TI  - Lead poisoning from an unexpected source in a 4-month-old infant.
AB  - Childhood lead poisoning is characteristically a disease that occurs between the
      second and third years of life, generally resulting from the child's ingestion of
      lead-based paint or dust. However, lead poisoning may also appear in the first
      year of life. The case of a 4-month-old infant is reported in which the
      preparation of infant formula in a lead-soldered samovar (urn) resulted in venous
      blood lead levels as high as 46 microg/dl. The samovar had been brought into the
      United States by the parents while on a visit to Iran. The infant was placed on
      chelation therapy with parenteral CaNa2EDTA followed by oral meso-2,3
      dimercaptosuccinic acid (DMSA) and d-penicillamine. This resulted in a rapid and
      substantial reduction in the blood lead level. Lead poisoning in infancy may have
      unusual etiologies such as in utero transmission of lead by lead-poisoned women.
      Because sources of lead poisoning in infancy may be unusual, a detailed
      environmental investigation may be necessary to identify the exact source.
      Children exposed to lead in the first 2 years of life have a special
      vulnerability to the neurotoxicity of lead, with the risk of enduring
      developmental handicaps. Continued public health initiatives to remove lead from
      the environment, in conjunction with routine lead screening of young children,
      will be key in meeting the goal of the Centers for Disease Control and Prevention
      to eliminate childhood lead poisoning by the year 2011.

PMID- 9618347
TI  - Assessing the cancer risk from environmental PCBs.
AB  - A new approach to assessing the cancer risk from environmental polychlorinated
      biphenyls (PCBs) considers both toxicity and environmental processes to make
      distinctions among environmental mixtures. New toxicity information from a 1996
      cancer study of four commercial mixtures strengthens the case that all PCB
      mixtures can cause cancer, although different mixtures have different potencies.
      Environmental processes alter PCB mixtures through partitioning, chemical
      transformation, and preferential bioaccumulation; these processes can increase or
      decrease toxicity considerably. Bioaccumulated PCBs are of greatest concern
      because they appear to be more toxic than commercial PCBs and more persistent in
      the body. The new approach uses toxicity studies of commercial mixtures to
      develop a range of cancer potency estimates and then considers the effect of
      environmental processes to choose appropriate values for representative classes
      of environmental mixtures. Guidance is given for assessing risks from different
      exposure pathways, less-than-lifetime and early-life exposures, and mixtures
      containing dioxinlike compounds.

PMID- 9618348
TI  - Association between air pollution and intrauterine mortality in Sao Paulo,
      Brazil.
AB  - The associations among daily counts of intrauterine mortality and pollutant
      concentrations (NO2, SO2, CO, O3, and particulate matter (3/4)10 microm) were
      investigated for the period ranging from January 1991 to December 1992 in the
      city of Sao Paulo, Brazil. We used Poisson regression techniques, adjusted for
      season and weather. The association between intrauterine mortality and air
      pollution was strong for NO2 (coefficient = 0.0013/ microg/m3; p<0.01) but lesser
      for SO2 (coefficient = 0.0005/ microg/m3; p<0.10) and CO (coefficient =
      0.0223/ppm; p<0.10). A significant association was observed when an index that
      combined these three pollutants was considered in the models instead of
      considering each pollutant individually (p<0.01). These associations exhibited a
      short time lag, not over 5 days. In addition, some evidence of fetal exposure to
      air pollution was obtained by disclosing a significant association between the
      levels of carboxyhemoglobin of blood sampled from the umbilical cord and ambient
      CO levels in children delivered by nonsmoking pregnant women in the period from
      May to July 1995. Our results suggest that air pollution in Sao Paulo may promote
      adverse health effects on fetuses.

PMID- 9618349
TI  - Adverse effect of air pollution on respiratory health of primary school children
      in Taiwan.
AB  - This study is a part of the Study On Air Pollution and Health In Taiwan
      (SOAP&HIT), an ongoing research project involving cooperation of several
      universities in Taiwan. In this study, the objective was to evaluate the effects
      of ambient air pollution on respiratory symptoms and diseases of school children,
      in addition to considering indoor air pollution. Six communities were selected:
      one community located in a rural area (Taihsi), two in urban areas (Keelung and
      Sanchung), and the other three in petrochemical industrial areas (Toufen, Jenwu,
      and Linyuan). We sampled 5,072 primary school students in six communities from
      the main study population of SOAP&HIT. Respiratory health was assessed by
      evaluation of the children's respiratory symptoms and diseases using a parent
      completed questionnaire. Data were analyzed using logistic regression analysis to
      compute odds ratios of adverse effect. The school children in the urban
      communities had significantly more respiratory symptoms (day or night cough,
      chronic cough, shortness of breath, and nasal symptoms) and diseases (sinusitis,
      wheezing or asthma, allergic rhinitis, and bronchitis) when compared with those
      living in the rural community. However, only nasal symptoms of children living in
      the petrochemical communities were more prevalent than in those living in the
      rural community. Although the association with ambient air pollution is
      suggestive, the cross-sectional study cannot confirm a causal relationship; thus
      further studies are needed.

PMID- 9618350
TI  - Effect of water temperature on dermal exposure to chloroform.
AB  - We have developed and applied a new measurement methodology to investigate dermal
      absorption of chloroform while bathing. Ten subjects bathed in chlorinated water
      while breathing pure air through a face mask. Their exhaled breath was delivered
      to a glow discharge source/ion trap mass spectrometer for continuous real-time
      measurement of chloroform in the breath. This new method provides abundant data
      compared to previous discrete time-integrated breath sampling methods. The method
      is particularly well suited to studying dermal exposure because the full face
      mask eliminates exposure to contaminated air. Seven of the 10 subjects bathed in
      water at two or three different temperatures between 30 degrees C and 40 degrees
      C. Subjects at the highest temperatures exhaled about 30 times more chloroform
      than the same subjects at the lowest temperatures. This probably results from a
      decline in blood flow to the skin at the lower temperatures as the body seeks to
      conserve heat forcing the chloroform to diffuse over a much greater path length
      before encountering the blood. These results suggest that pharmacokinetic models
      need to employ temperature-dependent parameters. Two existing models predict
      quite different times of about 12 min and 29 min for chloroform flux through the
      stratum corneum to reach equilibrium. At 40 degrees C, the time for the flux to
      reach a near steady-state value is 6-9 min. Although uptake and decay processes
      involve several body compartments, the complicating effect of the stratum corneum
      lag time made it difficult to fit multiexponential curves to the data; however, a
      single-compartment model gave a satisfactory fit.

PMID- 9618351
TI  - An anthropological approach to the evaluation of preschool children exposed to
      pesticides in Mexico.
AB  - In this comparative study, we compensated for many of the known variables that
      influence children's growth and development by selecting two groups of 4-5-year
      old Yaqui children who reside in the Yaqui Valley of northwestern Mexico. These
      children share similar genetic backgrounds, diets, water mineral contents,
      cultural patterns, and social behaviors. The major difference was their exposure
      to pesticides. Pesticides have been applied to the agricultural area of the
      valley since the late 1940s. In 1990, high levels of multiple pesticides were
      found in the cord blood of newborns and in breast milk. Building on
      anthropological methods for rapid rural appraisal of problems within the
      environment, a Rapid Assessment Tool for Preschool Children (RATPC) was developed
      to measure growth and development. The children of the agrarian region were
      compared to children living in the foothills, where pesticide use is avoided. The
      RATPC measured varied aspects of physical growth and abilities to perform, or
      function in, normal childhood activities. No differences were found in growth
      patterns. Functionally, the exposed children demonstrated decreases in stamina,
      gross and fine eye-hand coordination, 30-minute memory, and the ability to draw a
      person. The RATPC also pointed out areas in which more in-depth research on the
      toxicology of pesticides would be valuable.

PMID- 9618352
TI  - Metabolism of inorganic arsenic in children with chronic high arsenic exposure in
      northern Argentina.
AB  - This study concerns the metabolism of inorganic arsenic (As) in children in three
      villages in northern Argentina: San Antonio de los Cobres and Taco Pozo, each
      with about 200 microg As/l in the drinking water, and Rosario de Lerma, with 0.65
      microg As/l. Findings show that the concentrations of As in the blood and urine
      of the children in the two As-rich villages were on average 9 and 380 microg/l,
      respectively, the highest ever recorded for children. The concentrations were
      about 10 and 30 times higher for blood and urine, respectively, than in Rosario
      de Lerma. Total As in urine was only slightly higher than the sum of metabolites
      of inorganic As (U-Asmet), i.e., inorganic As, methylarsonic acid (MMA), and
      dimethylarsinic acid (DMA); this shows that inorganic As was the main form of As
      ingested. In contrast to previous studies on urinary metabolites of inorganic As
      in various population groups, the children and women in the present study
      excreted very little MMA. Thus, there seems to be a polymorphism for the enzymes
      (methyltransferases) involved in the methylation of As. Interestingly, the
      children had a significantly higher percentage of inorganic As in urine than the
      women, about 50% versus 32%. Also, the percentage of inorganic As in the children
      is considerably higher than in previous studies on children (about 13% in the two
      studies available) and adults (about 15-25%) in other population groups. This may
      indicate that children are more sensitive to As-induced toxicity than adults, as
      the methylated metabolites bind less to tissue constituents than inorganic As. In
      the children, the percentage inorganic arsenic in urine decreased, and the
      percentage of DMA increased with increasing U-Asmet, indicating an induction of
      As methylation with increasing exposure.

PMID- 9618353
TI  - Hyperproduction of erythropoietin in nonanemic lead-exposed children.
AB  - Lead (Pb) poisoning has numerous effects on the erythropoietic system, but the
      precise mechanism whereby high dose exposure causes anemia is not entirely clear.
      We previously reported that Pb exposure is associated with depressed serum
      erythropoietin (EPO) in pregnant women residing in a Pb mining town and in a
      nonexposed town in Kosovo, Yugoslavia. In a prospective study, we tested the
      hypothesis that blood Pb concentration (BPb) may be associated with depressed EPO
      in children. BPb, hemoglobin (Hgb), and serum EPO were measured at ages 4.5, 6.5,
      and 9.5 years in 211, 178, and 234 children, respectively. At 4.5 years of age,
      mean BPbs were 38.9 and 9.0 microg/dl in the exposed and nonexposed towns,
      respectively; BPbs gradually declined to 28.2 and 6.5 microg/dl, respectively, by
      age 9.5 years. No differences were found in Hgb at any age. At age 4. 5 years, a
      positive association between BPb and EPO (beta = 0.21; p = 0.0001), controlled
      for Hgb, was found. The magnitude of this association declined to 0.11 at age 6.5
      years (p = 0.0103) and 0.03 at age 9.5 years (p = 0.39). These results were
      confirmed using repeated measures analyses. We concluded that in Pb-exposed
      children, the maintenance of normal Hgb requires hyperproduction of EPO. With
      advancing age (and continuing exposure), this compensatory mechanism appears to
      be failing, suggesting a gradual loss of renal endocrine function due to Pb
      exposure.

PMID- 9618354
TI  - The specter of sprawl.

PMID- 9618355
TI  - Drugs from dinoflagellates.

PMID- 9618356
TI  - Children's Environmental Health Network, Emeryville, California.
AB  - Research is one of the cornerstones of environmental health, providing the
      foundation for sound public policy and for appropriate education of communities
      and professionals in a myriad of disciplines. Until very recently, little
      research in environmental health focused on exposure patterns and health outcomes
      for children. Pediatric medicine shows that children are not just little adults;
      they are uniquely vulnerable.

PMID- 9618376
TI  - Thanks for the memories 

PMID- 9618375
TI  - Characterization of kinetics of anti-Trichinella spiralis newborn larvae immunity
      in rats.
AB  - The kinetics of anti-T. spiralis newborn larvae (NBL) immunity and its dose
      effects were studied in vivo. Rats were either immunized with newborn larvae i.v.
      or muscle larvae per os and challenged with newborn larvae either i.v. or i.p. on
      day 7 up to day 27 after immunization. Immunity was assessed by examining the
      muscle larvae burden or the larval recovery from the peritoneal cavity. Recovered
      newborn larvae were further examined for cell adherence and viability. Results
      indicate that as early as 9 days after infection and only 3 days after newborn
      larvae production in vivo, specific anti-newborn larvae immunity was developed.
      Peritoneal cells as well as blood cells adhered to the cuticles of the larvae and
      killed them. When different doses of immunization were examined, it was found
      that 2,000 muscle larvae per os induced the strongest immunity as compared to
      500, 5,000 or 6,000. Such immunity maintained its strength when challenge
      infection with newborn larvae reached 50,000 dosage and it declined significantly
      when the dose reached 100,000. This indicates that the immune cells and
      antibodies are not re-deployed.

PMID- 9618377
TI  - Catalytic activation of extracellular signal-regulated kinases induces cyclin D1
      expression in primary tracheal myocytes.
AB  - We have demonstrated that extracellular signal-regulated kinases (ERKs) and
      cyclin D1 are required for bovine tracheal myocyte DNA synthesis. We hypothesized
      that catalytic activation by ERKs may regulate cyclin D1 expression in these
      cells. To test this hypothesis, we examined the effects of two inhibitors of ERKs
      and two reagents that increase the level of activated ERKs on cyclin D1 protein
      abundance and promoter activity. ERK activity was inhibited either by PD98059, a
      synthetic inhibitor of mitogen-activated protein kinase (MAPK)/ERK kinase (MEK),
      the upstream signaling intermediate required and sufficient for ERK activation,
      or by transient transfection with a dominant-negative mutant of MEK1 (MEK-2A).
      The level of activated ERKs was increased by transient transfection with either a
      constitutively active form of MEK1 (MEK-2E) or wild-type ERK2 (MAPKwt). Cyclin D1
      expression was assessed either by immunoblot or cotransfection with the full
      length cyclin D1 promoter subcloned into a luciferase reporter. We found that
      pretreatment of bovine tracheal myocytes with PD98059 significantly attenuated
      platelet- derived growth factor (PDGF)-induced cyclin D1 protein abundance.
      Furthermore, transfection with MEK-2A reduced PDGF-induced cyclin D1 promoter
      activity. Finally, transfection with either MEK-2E or MAPKwt induced cyclin D1
      promoter activity in the absence of growth factor treatment. We conclude that
      catalytic activation of ERKs regulates cyclin D1 expression in airway smooth
      muscle cells.

PMID- 9618378
TI  - Overexpression of the Na+,K+-ATPase alpha1 subunit increases Na+,K+-ATPase
      function in A549 cells.
AB  - We hypothesized that viral mediated transfer of Na+,K+-ATPase subunit genes to
      alveolar epithelial cells to overexpress Na+, K+-ATPase could increase Na+,K+
      ATPase function. We produced replication-deficient human type 5 adenoviruses that
      contained cytomegalovirus (CMV)-driven cDNAs for the rat alpha1 and beta1
      subunits of Na+,K+-ATPase (AdMRCMValpha1 and AdMRCMVbeta1, respectively). These
      viruses were used to transduce human adenocarcinoma cells (A549) in culture.
      Na+,K+-ATPase function was increased by 2.5-fold in the AdMRCMValpha1-infected
      cells. Sham and AdMRCMVbeta1-infected cells, and cells infected by a CMV-driven
      beta-galactosidase-expressing adenovirus, had no increases in Na+, K+-ATPase
      activity. A549 cells infected with multiplicities of infection of 10-200 of
      AdMRCMValpha1 demonstrated expression of a rat alpha1 mRNA and increased alpha1
      protein; no change in beta1 message or protein was noted. Ouabain sensitivity was
      measured in A549 cells following infection with AdMRCMValpha1. In contrast to
      controls, AdMRCMValpha1-infected cells demonstrated two IC50s. The first was
      similar to the IC50s of the controls; the second IC50 was 2 logs greater than the
      first, consistent with the presence of both the rat and human alpha1 isozymes.
      These results demonstrate for the first time that adenoviruses can be used to
      augment Na+,K+-ATPase function.

PMID- 9618379
TI  - Lef1 transcription factor expression defines airway progenitor cell targets for
      in utero gene therapy of submucosal gland in cystic fibrosis.
AB  - Cystic fibrosis (CF) has emerged as a paradigm disorder for assessing the utility
      of gene therapy in the treatment of genetic diseases. It is hypothesized that
      submucosal glands may play an important role in the pathophysiology of CF lung
      disease. However, this region poses several significant obstacles for gene
      therapy due to its inaccessibility from the lumen of adult proximal airways. In
      utero gene therapy to correct submucosal gland dysfunction in CF provides an
      attractive alternative strategy to target gland progenitor cells prior to gland
      formation and morphogenesis. Such approaches will require the use of integrating
      vectors capable of transducing expanding stem-cell/progenitor-cell populations in
      the lung. We described a newborn-ferret model of the proximal airway which was
      used to evaluate the phenotypic characteristics of submucosal gland progenitors
      and to test gene therapy strategies for targeting these cell types. To this end,
      we have isolated the ferret cDNA to the lymphoid enhancing factor 1 (Lef1) and
      have demonstrated that its mRNA expression specifically defines a subset of
      surface airway epithelial progenitor cells involved in the formation of
      primordial submucosal gland buds and subsequent gland morphogenesis. Such
      findings suggest that the transcriptional switch regulating activation of Lef1
      expression defines the phenotype of early submucosal gland progenitor cells. In
      an effort to prove the principle of gene targeting to this progenitor-cell
      population, we evaluated the efficiency of recombinant retroviral vectors to
      target submucosal glands in a xenograft model system. Findings from these studies
      demonstrated successful gene targeting to progenitor cells of submucosal gland
      buds which was stable throughout subsequent gland development. In summary, these
      studies have provided evidence for the existence of phenotypically distinct
      submucosal gland progenitor cells which represent appropriate targets for gene
      therapy of submucosal glands in CF.

PMID- 9618380
TI  - Allergen challenge increases cell traffic between bone marrow and lung.
AB  - Increases in inflammatory-cell progenitors have been demonstrated in the bone
      marrow (BM) after inhalation of Ascaris suum in dogs at the time of allergen
      induced airway hyperresponsiveness (AHR). The aim of this study was to evaluate
      the effect of allergen challenge on trafficking of inflammatory cells and their
      progenitors from the BM to the lung, using a marker of proliferating cells,
      bromodeoxyuridine (BrdU). BrdU is a thymidine analogue taken up by the DNA of
      dividing cells, and can be detected with immunohistochemistry (IHC). The
      development of AHR was assessed through acetylcholine (ACh) airway responsiveness
      before and after allergen inhalation. Two groups of dogs were matched for the
      degree of AHR after a screening allergen challenge. On the study day, one group
      inhaled allergen (n = 8) and one group inhaled diluent (n = 8). All dogs received
      equal bolus injections of BrdU before and at 5 h after challenge. Blood samples
      were taken before challenge and at 5 h and 24 h after challenge, and BM aspirate
      and bronchoalveolar lavage (BAL) samples were taken 24 h after challenge. BrdU
      positive cells were detected in cytospin preparations of these samples, using
      IHC. Allergen inhalation caused AHR (P < 0.05) at 24 h after allergen challenge,
      and also an increase in BrdU-positive cells in blood, which was 5.7 +/- 0.6%
      (mean +/- SEM) after allergen challenge and 2.5 +/- 0.7% after diluent (P <
      0.005); in BM the increase in BrdU-positive cells was 27.0 +/- 3.4% after
      allergen challenge and 18.9 +/- 3.2% after diluent (P = 0.1); and in BAL the
      increase was 3.2 +/- 0.4% after allergen challenge and 0.8 +/- 0.3% after diluent
      (P < 0.005). There was a significant correlation between the number of BAL
      neutrophils and the percentage of BrdU-positive BAL cells (r2 = 0.54, P < 0.05).
      These results demonstrate an allergen-induced increase in proliferating cells,
      probably in the BM, and indicate that such cells traffic through the circulation
      into the lungs in response to allergen inhalation.

PMID- 9618381
TI  - Increased vascular endothelial growth factor production in the lungs of rats with
      hypoxia-induced pulmonary hypertension.
AB  - Vascular endothelial growth factor (VEGF) is a potent mitogenic and permeability
      factor targeting predominantly endothelial cells. At least two tyrosine kinase
      receptors, Flk-1 and Flt-1, mediate its action and are mostly expressed by
      endothelial cells. VEGF and VEGF receptor expression are upregulated by hypoxia
      in vivo and the role of VEGF in hypoxia-induced angiogenesis has been extensively
      studied in a variety of disease entities. Although VEGF and its receptors are
      abundantly expressed in the lung, their role in hypoxic pulmonary hypertension
      and the accompanying vascular remodeling are incompletely understood. We report
      in this in vivo study that hypoxia increases mRNA levels for both VEGF and Flk-1
      in the rat lung. The kinetics of the hypoxic response differ between receptor and
      ligand: Flk-1 mRNA showed a biphasic response to hypoxia with a significant, but
      transient, rise in mRNA levels observed after 9-15 h of hypoxic exposure and the
      highest levels noted after 3 wk. In contrast, VEGF mRNA levels did not show a
      significant increase with acute hypoxia, but increased progressively after 1-3 wk
      of hypoxia. By in situ hybridization, VEGF mRNA was localized predominantly in
      alveolar epithelial cells with increased signal in the lungs of hypoxic animals
      compared with controls. Immunohistochemical staining with anti-VEGF antibodies
      localized VEGF peptide throughout the lung parenchyma and was increased in
      hypoxic compared with normoxic animals. Furthermore, hypoxic animals had
      significantly higher circulating VEGF concentrations compared with normoxic
      controls. Lung vascular permeability as measured by extravasation of Evans Blue
      dye was not significantly different between normoxic and hypoxic animals,
      although a tendency for increased permeability was seen in the hypoxic animals.
      These findings suggest a possible role for VEGF in the pulmonary response to
      hypoxia.

PMID- 9618382
TI  - Reduction of antigen-induced airway hyperreactivity and eosinophilia in ICAM-1
      deficient mice.
AB  - A murine model of asthma is described in which we examined the role of
      intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of airway
      reactivity, pulmonary eosinophilia, and inflammation. We sensitized wild-type
      control [C57BL/6J, (+/+)] and ICAM-1 knockout [C57BL/6J-ICAM-1, (-/-)] mice to
      ovalbumin (OVA), and challenged them with OVA delivered by aerosol (OVA-OVA) to
      induce a phenotype consistent with an asthmatic response. Bronchial
      responsiveness to methacholine and counts of cell numbers and measurements of
      eosinophil content and cytokine levels in bronchoalveolar lavage fluid (BALF)
      were significantly attenuated in ICAM-1(-/-) mice as compared with (+/+) mice. We
      also showed that the absence of ICAM-1 had no significant affects on the
      production of serum IgE antibody, but did have an effect on ex vivo lymphocyte
      proliferation. Additionally, immunohistochemistry: (1) revealed increased
      staining for vascular cell adhesion molecule-1 (VCAM-1) after antigen challenge
      in the ICAM-1(-/-) mice but not in the ICAM-1(+/+) controls; and (2) confirmed
      the presence of alternatively spliced forms of ICAM-1 in the lungs of ICAM-1(-/-)
      mice. Thus, despite the availability of alternate adhesion pathways in ICAM-1(-/
      ) mice, the absence of ICAM-1 prevented eosinophils from entering the airways. In
      summary, we found that the ICAM-1 knockout mice exhibited a significantly
      inhibited response to aerosol antigen challenge for most of the parameters
      examined, and conclude that ICAM-1 is an important ligand mediating T-cell
      proliferation in response to antigen, eosinophil migration into the airways, and
      the development of airway hyperreactivity (AHR) in allergen-sensitized and 
      challenged mice.

PMID- 9618383
TI  - Programmed cell death contributes to postnatal lung development.
AB  - The rat lung undergoes the phase of maturation of the alveolar septa and of the
      parenchymal microvascular network mainly during the third postnatal week.
      Speculating that programmed cell death may contribute to the thinning of the
      alveolar septa, we searched for the presence of DNA fragmentation in rat lungs
      between postnatal days 6 and 36 using the TUNEL procedure. The number of positive
      nuclei was compared at different days. We observed an 8-fold increase of
      programmed cell death toward the end of the third week as compared to the days
      before and after this time point. The precise timing of the appearance of the
      peak depended on the size of the litter. Double-labeling for DNA fragmentation
      (TUNEL) and for type I and type II epithelial cells (antibodies E11 and MNF-116),
      as well as morphologic studies at electron microscopic level, revealed that
      during the peak of programmed cell death mainly fibroblasts and type II
      epithelial cells were dying. While both dying cell types were TUNEL-positive,
      nuclear fragments and apoptotic bodies were exclusively observed in the dying
      fibroblasts. We conclude that programmed cell death is involved in the structural
      maturation of the lung by reducing the number of fibroblasts and type II
      epithelial cells in the third postnatal week. We observed that the dying
      fibroblasts are cleared by neighboring fibroblasts in a later stage of apoptosis,
      and we hypothesize that type II epithelial cells are cleared by alveolar
      macrophages in early stages of the programmed cell death process.

PMID- 9618384
TI  - Expression of the Bcl-2 protein in nasal epithelia of F344/N rats during mucous
      cell metaplasia and remodeling.
AB  - Exposure to ozone induces mucous cell metaplasia in rat airway epithelia. During
      the regeneration process, apoptotic mechanisms may be responsible for eliminating
      metaplastic cells. Therefore, the present study investigated expression of Bcl-2,
      a regulator of apoptosis, in ozone-induced mucous cell metaplasias. Adjacent
      metaplastic mucous cells in nasal airway epithelia that were exposed to ozone
      were heterogeneous in their expression of Bcl-2; some cells expressed high
      levels, whereas others expressed low levels or no Bcl-2. On Western blot
      analysis, Bcl-2 was detected in protein extracts from nasal epithelia of rats
      exposed to 0.5 ppm ozone for 1 mo but not in control rats exposed to filtered
      air. The number of metaplastic mucous cells in transitional epithelia of rat
      nasal airways was increased from 0 to about 200 after 3 and 6 mo of exposure to
      ozone; only 0 to 10 metaplastic mucous cells remained after a recovery period of
      13 wk in rats exposed to ozone for 3 mo. The number of mucous cells of the
      respiratory epithelium lining the midseptum did not change after ozone exposure
      or recovery. The percentage of Bcl-2-positive cells lining the midseptum
      increased from 7 to 14% after a 3- and 6-mo ozone exposure, respectively. In
      transitional epithelia of the lateral wall and the nasoturbinates and
      maxilloturbinates, 35 to 55% of cells were Bcl-2-positive after a 1-mo exposure
      and 10 to 18% after both a 3- and a 6-mo exposure to ozone. Bcl-2 reactivity
      decreased to 0 to 8% after a recovery period of 13 wk. These observations suggest
      that Bcl-2 plays a role in the development and resolution of mucous cell
      metaplasias. This model may be useful in uncovering the role of Bcl-2 during the
      development and maintenance of metaplastic mucous cells. Disregulation of Bcl-2
      expression may be responsible for the sustained mucous cell metaplasia in
      asthmatics or may allow cells to accumulate and become more susceptible to
      transformation leading to neoplasia.

PMID- 9618385
TI  - Lung lymphocytes proliferate minimally in the murine pulmonary immune response to
      intratracheal sheep erythrocytes.
AB  - The importance of in situ lymphocyte proliferation for net accumulation of lung
      lymphocytes during pulmonary immune responses and in immunologic lung diseases
      remains uncertain. Accordingly, we studied the experimental pulmonary immune
      response of antigen-primed C57BL/6 mice to intratracheal challenge with the
      particulate antigen sheep red blood cells. Uptake of nucleotide analogs
      (bromodeoxyuridine in vivo and tritiated thymidine in vitro), expression of the
      cell activation antigens CD25 and CD69 by flow cytometry, and response to the
      antimitotic agent hydroxyurea (in vivo) were measured. Although many lung
      lymphocytes and CD4+ T cells were CD25+ and CD69+, indicating recent activation,
      all techniques demonstrated that lung lymphocytes proliferated minimally in vivo.
      Blockade of cell division by hydroxyurea administration for 24 h did not
      significantly decrease lung lymphocyte accumulation on Day 3 after challenge.
      Lung lymphocytes also proliferated minimally in vitro (even on macrophage removal
      and despite addition of exogenous interleukin [IL]-2 or IL-4). However, lung
      lymphocytes responded vigorously to mitogens (immobilized anti-CD3,
      phytohemagglutinin, or concanavalin A), excluding global unresponsiveness to
      restimulation. Thus, in this model of pulmonary immunity, accumulation of lung
      lymphocytes does not require local T-cell proliferation and presumably depends
      instead on recruitment.

PMID- 9618386
TI  - Cell-matrix interactions modulate 92-kD gelatinase expression by human bronchial
      epithelial cells.
AB  - We have previously reported that primary human bronchial epithelial cells (HBECs)
      cultured on types I + III collagen were able to differentially regulate the
      production of major constitutive 92-kD gelatinase, minor 72-kD gelatinase, and
      their tissue-specific inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1)
      in response to lipopolysaccharide (LPS) or proinflammatory cytokines, suggesting
      that HBECs may be involved in vivo in the active remodeling of the underlying
      extracellular matrix (ECM). In this study, we examined the possible effects of
      specific type IV collagen as compared with types I + III collagen on HBEC
      behavior and function. We investigated 92-kD gelatinase and TIMP-1 expression
      with zymography and reverse zymography, respectively, at the protein level, and
      with quantitative reverse transcription-polymerase chain reaction (RT-PCR) at the
      mRNA level. Results showed similar morphologic features and identical
      proliferation rates of HBECs in response to the two matrix substrates.
      Nevertheless, differences at the protein and mRNA levels between HBEC cultures on
      type IV collagen and on types I + III collagen included: (1) a lower basal level
      of 92-kD gelatinase production; (2) less upregulation of 92-kD gelatinase in
      response to LPS endotoxin or to the proinflammatory cytokines interleukin-1beta
      (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha); and (3) loss of
      activation of the proforms of the 92-kD and 72-kD gelatinases. These findings,
      together with the maintenance of TIMP-1 expression, strongly suggest that type IV
      collagen used as a matrix substratum is associated with a homeostatic HBEC
      phenotype, and limits the ability of HBECs to degrade the matrix. In contrast,
      types I + III collagen may be associated with a matrix resorption phenotype
      corresponding to active matrix remodeling and repair. Thus, the ECM underlying
      HBECs may modulate matrix remodeling by HBECs, particularly in response to
      inflammatory processes during acute lung injury.

PMID- 9618387
TI  - Angiotensin II induces hypertrophy of human airway smooth muscle cells:
      expression of transcription factors and transforming growth factor-beta1.
AB  - Increased smooth muscle mass due to hyperplasia and hypertrophy of airway smooth
      muscle (ASM) cells is a common feature in asthma. Angiotensin II (Ang II), a
      potent vasoconstrictor and mitogen for a wide variety of cells, has recently been
      implicated in bronchoconstriction in asthmatics. However, a possible mitogenic
      role as well as underlying molecular mechanisms of this octapeptide in human ASM
      cells are not yet known. We studied the effects of Ang II on ASM cell
      proliferation and growth and on the expression of three transcription factors,
      egr-1, c-fos, and c-jun, as well as a cytokine, transforming growth factor-beta1
      (TGF-beta1). Human ASM cells were isolated by enzymatic digestion of bronchial
      smooth muscle obtained from lung resection tissue. Confluent cells were growth
      arrested and subsequently incubated with Ang II (100 nM) for different time
      periods and processed for the measurement of cell growth and gene expression. Ang
      II significantly induced DNA and protein synthesis in human ASM cells at 8 h,
      resulting in a net increase in the accumulation of protein over DNA (i.e.,
      cellular hypertrophy) at 16 h of incubation. Cell counts and MTT-reduction assay,
      however, showed no increase in cell number as a result of Ang II stimulation. Ang
      II stimulated the expression of egr-1 and c-fos as early as 15 min, reaching
      maximum levels at 45 min, whereas the expression of c-jun peaked at 2 h of Ang II
      exposure. Furthermore, steady-state mRNA levels of TGF-beta1 were upregulated by
      Ang II after 4 h and reached peak levels at 16 h of incubation. Secretion of
      biologically active TGF-beta1 from human ASM cells was significantly (P <= 0.02)
      enhanced by Ang II incubation after 8 h, which remained elevated until 24 h. Our
      results suggest that the Ang II-induced transient early expression of
      transcription factors may regulate autocrine genes like TGF-beta1, of which the
      subsequent late upregulation could contribute to cellular hypertrophy during, for
      example, airway remodeling in asthma.

PMID- 9618388
TI  - Surfactant protein-A reduces binding and phagocytosis of pneumocystis carinii by
      human alveolar macrophages in vitro.
AB  - Surfactant protein-A (SP-A) levels are increased in Pneumocystis carinii
      pneumonia, but the role of SP-A in the pathogenesis of P. carinii pneumonia is
      not completely understood. This study investigated the effect of SP-A on the in
      vitro binding and phagocytosis of P. carinii by normal human alveolar macrophages
      (AM). Determination of binding and phagocytosis was done with a fluorescence
      based assay, utilizing fluorescein isothiocyanate (FITC)-labeled P. carinii.
      Binding and phagocytosis of P. carinii to AM correlated inversely with the levels
      of SP-A present on the surface of the organisms (r = -0.6323, P = 0.0086; and r =
      -0.9827, P < 0.0001, respectively). The addition of exogenous SP-A to organisms
      with low surface-associated SP-A reduced P. carinii binding by 30% (P < 0.05) and
      reduced phagocytosis by 20% (P < 0.05), whereas this effect was reversed with
      ethylenediamine tetraacetic acid (EDTA) or anti-SP-A antibody. Furthermore,
      binding and phagocytosis were enhanced after enzymatic removal of P. carinii
      surface-associated SP-A, and this effect was reversed with the addition of
      exogenous SP-A. The observed inhibitory effect of SP-A on P. carinii binding and
      phagocytosis reflected binding of SP-A to the organisms rather than a direct
      effect of SP-A on the macrophages. These data suggest that increased levels of SP
      A may contribute to the pathogenesis of P. carinii pneumonia through binding to
      the surface of the organism and interfering with AM recognition of this
      opportunistic pulmonary pathogen.

PMID- 9618389
TI  - Ontogenesis of nitric oxide synthases in the ventilatory muscles.
AB  - Nitric oxide (NO) acts as an endogenous mediator in mature skeletal muscle. In
      this study, we investigated the regulation of the endothelial (eNOS) and neuronal
      (nNOS) isoforms of nitric oxide synthase (NOS) in skeletal-muscle development
      (rat diaphragm). Muscle NOS activity, nNOS and eNOS protein, and mRNA expressions
      were markedly increased during the late gestational and early postnatal periods.
      Expression of both isoforms, however, declined progressively thereafter.
      Similarly, argininosuccinate lyase and argininosuccinate synthetase, both
      involved in the recycling of L-citrulline to L-arginine, were expressed at high
      levels in rat embryonic and neonatal diaphragms, with gradual reduction in their
      expression during late postnatal development. Immunostaining revealed extensive
      nNOS expression at the sarcolemma in neonatal and mature diaphragms, whereas eNOS
      expression was limited to the endothelium. Both neonatal and adult diaphragms
      expressed an alternatively spliced nNOS isoform with an insert of 34 amino acids
      between exons 16 and 17. In vitro-generated muscle force rose significantly after
      NOS inhibition in both neonatal and adult diaphragms, but the magnitude of force
      augmentation was larger in adult than in neonatal diaphragm. These results
      indicate that constitutive NOS isoforms are developmentally regulated in skeletal
      muscles, suggesting multiple roles for NO in developing and mature skeletal
      muscle fibers.

PMID- 9618390
TI  - Methotrexate inhibition of inducible nitric oxide synthase in murine lung
      epithelial cells in vitro.
AB  - Nitric oxide (NO) is produced in lung epithelial cells by nitric oxide synthases
      (NOSs), which can enhance inflammation and edema formation. The inducible NOS
      (iNOS, type II NOS) has been shown to be increased in lung disorders such as
      asthma. Therapy for asthma includes antiinflammatory agents such as
      corticosteroids and antineoplastic agents such as methotrexate (MTX). We
      hypothesized that NO production by epithelial cells in vitro would be attenuated
      by MTX, and that this effect would be additive with corticosteroids. In order to
      test this hypothesis, cells from the murine lung epithelial-cell line LA-4 were
      cultured to confluence and stimulated to express iNOS and produce NO by cytomix,
      a combination of human tumor necrosis factor-alpha (TNF-alpha), human interleukin
      1beta (IL-1beta) and murine interferon-gamma (IFN-gamma). Nitrite and nitrite +
      nitrate were measured in the culture supernatant fluids as an index of NO
      production. MTX caused a dose- and time-dependent inhibition of nitrite and
      nitrite + nitrate (P < 0.05, all comparisons). Importantly, the inhibition of NO
      production by MTX (10(-3) M) was additive with dexamethasone (10(-5) to 10(-9)
      M), but cyclophosphamide, bleomycin, and cytosine-beta-D-arabinofuranoside (Ara
      C), other antineoplastic agents, caused no inhibition of NO production. To
      investigate the mechanism of NO inhibition with MTX, we added
      tetrahydrobiopterin, which reversed the inhibition. MTX had no effect on the
      expression of iNOS on Western blotting or iNOS mRNA on Northern blotting. These
      data show that MTX inhibits NO production by iNOS in murine lung epithelial cells
      in vitro and that MTX produces added inhibition with corticosteroids, and suggest
      a potential strategy for reducing NO production in vivo.

PMID- 9618392
TI  - Fetal nicotine or cocaine exposure: which one is worse?
AB  - Despite extensive adverse publicity, tobacco use continues in approximately 25%
      of all pregnancies in the United States, overshadowing illicit drugs of abuse,
      including cocaine. The societal cost of maternal smoking is seen most readily in
      underweight newborns, in high rates of perinatal morbidity, mortality and Sudden
      Infant Death Syndrome and in persistent deficits in learning and behavior. We
      have designed animal models of nicotine exposure to prove that nicotine itself is
      a neuroteratogen, thus providing a causative link between tobacco exposure and
      adverse perinatal outcomes. In particular, nicotine infusion paradigms that, like
      the transdermal patch used in man, produce drug exposure without the confounds of
      other components of tobacco or of episodic hypoxic-ischemic insult, have enabled
      a mechanistic dissection of the role played by nicotine in fetal brain damage.
      Nicotine targets specific neurotransmitter receptors in the fetal brain,
      eliciting abnormalities of cell proliferation and differentiation, leading to
      shortfalls in the number of cells and eventually to altered synaptic activity.
      Because of the close regulatory association of cholinergic and catecholaminergic
      systems, adverse effects of nicotine involve multiple transmitter pathways and
      influence not only the immediate developmental events in fetal brain, but also
      the eventual programming of synaptic competence. Accordingly, defects may appear
      after a prolonged period of apparent normality, leading to cognitive and learning
      defects that appear in childhood or adolescence. Comparable alterations occur in
      peripheral autonomic pathways, leading to increased susceptibility to hypoxia
      induced brain damage, perinatal mortality and Sudden Infant Death. Identifying
      the receptor-driven mechanisms that underlie the neurobehavioral damage caused by
      fetal nicotine exposure provides a rational basis for decisions about nicotine
      substitution therapy for smoking cessation in pregnancy. In contrast to the
      effects of nicotine, animal models of crack cocaine use in pregnancy indicate a
      more restricted spectrum of effects, a reflection of differences both in
      pharmacokinetics and pharmacodynamics of the two drugs. Notably, although
      cocaine, like nicotine, also targets cell replication, its effects are short
      lived, permitting recovery to occur in between doses, so that the eventual
      consequences are much less severe. To some extent, the effects of cocaine on
      brain development resemble those of nicotine because the two share cardiovascular
      actions (vasoconstriction) that, under some circumstances, elicit fetal hypoxia
      ischemia. In light of the fact that nearly all crack cocaine users smoke
      cigarettes, the identification of specific developmental effects of cocaine may
      prove difficult to detect. Although scientists and the public continue to pay far
      more attention to fetal cocaine effects than to those of nicotine or tobacco use,
      a change of focus to concentrate on tobacco could have a disproportionately
      larger impact on human health.

PMID- 9618391
TI  - CD44 and CD69 represent different types of cell-surface activation markers for
      human eosinophils.
AB  - Eosinophils (EOS) purified from peripheral blood or late-phase bronchoalveolar
      lavage (BAL) were analyzed with 473 monoclonal antibodies (mAbs) from the Fifth
      International Workshop on Human Leukocyte Antigens in an attempt to identify
      markers of EOS activation. Two strategies were used: (1) to look for surface
      markers absent on fresh EOS but present after in vivo activation (e. g., in late
      phase BAL fluid [BALF]) or after in vitro culture for up to 72 h with cytokines
      (<= 10 ng/ml of interleukin-3 [IL-3], IL-5, or granulocyte-macrophage colony
      stimulating factor [GM-CSF]); and (2) to look for markers constitutively
      expressed on fresh EOS that were increased after activation in vivo or after
      culture in vitro. With indirect immunofluorescence and flow cytometry, the first
      approach revealed that among approximately 350 mAbs tested, only those
      recognizing CD69 became bound to late-phase BALF EOS or cytokine-cultured EOS,
      but not to fresh EOS. Using the second approach, we observed statistically
      significant concentration- and time-dependent increases in CD44 expression in EOS
      cultured with IL-3, IL-5, or GM-CSF (approximately 2-fold increase in
      fluorescence intensity, P < 0.05), but not with interferon-gamma (IFN-gamma) (up
      to 100 ng/ml), whereas levels of 15 other constitutively expressed markers were
      unchanged. Despite increased expression, neither fresh nor cytokine-cultured EOS
      adhered to immobilized hyaluronate, a ligand for CD44. Additionally, simultaneous
      comparison of hypodense (specific gravity < 1.085 g/liter) and normodense
      (specific gravity > 1.085 g/liter) EOS from allergic donors consistently revealed
      higher levels of CD44 expression (approximately 3- to 8-fold) but not CD69
      expression on hypodense EOS. We conclude that CD69 and CD44 represent different
      types of activation markers for human EOS. These findings may be useful in
      assessing the state of EOS activation in vitro and in vivo.

PMID- 9618393
TI  - The preclinical pharmacological profile of the potent and selective leukotriene
      B4 antagonist CP-195543.
AB  - CP-195543 [(+)-2-(3-benzyl-4-hydroxy-chroman-7-yl)-4-trifluoromethyl-benzoic
      acid] is a structurally novel, selective and potent leukotriene B4 (LTB4)
      receptor antagonist. In vitro CP-195543 inhibited [3H]LTB4 binding to high
      affinity LTB4 receptors on human neutrophils (HN) and murine spleen membranes
      with IC50 values of 6.8 nM (Ki = 4.9 nM) and 37.0 nM (Ki = 26.9 nM),
      respectively. CP-195543 inhibited human and mouse neutrophil chemotaxis mediated
      by LTB4 with IC50 values of 2.4 nM and 7.5 nM, respectively. Evidence of
      noncompetitive antagonist effects on the HN high-affinity LTB4 receptor was
      obtained by Scatchard analysis of [3H]LTB4 binding to and chemotaxis of HN to
      LTB4. Scatchard analyses of [3H]LTB4 binding to low-affinity receptors on HN
      indicated that CP-195543 acted as a competitive antagonist at this receptor, and
      inhibition of LTB4-mediated CD11b up-regulation on HN was inhibited competitively
      by CP-195543 (pA2 = 7.66). In whole blood, CP-195543 also blocked CD11b up
      regulation on HN (pA2 = 7.12) and murine neutrophils (pA2 = 7.06) with a similar
      potency. LTB4-mediated CD11b up-regulation on human monocytes and eosinophils in
      whole blood were inhibited by CP-195543 with IC50 values of 270 nM and 420 nM,
      respectively. CP-195543 at 10 microM failed to inhibit HN chemotaxis and CD11b up
      regulation mediated through alternative (i.e., complement fragment 5a,
      interleukin-8, platelet-activating factor) G-protein-coupled chemotactic factor
      receptors. In vivo, after oral administration, CP-195543 blocked LTB4-mediated
      neutrophil infiltration in guinea pig and murine skin with ED50 values of 0.1
      mg/kg and 2.8 mg/kg p.o., respectively. When administered in osmotic pumps, CP
      195543 reduced the clinical symptoms and attendant weight loss in an IL-1
      exacerbated murine model of collagen-induced arthritis with half-maximal effects
      associated with plasma drug levels of 0.4 to 0.5 microg/ml. Collectively these
      data provide evidence of the in vitro potency and in vivo efficacy of a novel
      LTB4 antagonist and support its clinical evaluation in a variety of inflammatory
      diseases in man.

PMID- 9618394
TI  - Novel single-point plasma or saliva dextromethorphan method for determining
      CYP2D6 activity.
AB  - O-Demethylation of dextromethorphan co-segregates with 4-hydroxylation of
      debrisoquin and is used for CYP2D6 phenotyping. In most previous studies, 8-h
      urinary samples were collected for determining the dextromethorphan metabolic
      ratio (dextromethorphan/dextrorphan molar ratio). In addition, a salivary
      sampling at 3 h had been suggested for the phenotyping. To evaluate the
      repeatability and validity of previously reported and other potential phenotyping
      methods, we determined the metabolic ratios from urine samples (for various
      intervals), or from plasma or saliva (at varying time points) after repetitive
      single doses of immediate-release or repetitive multiple doses of controlled
      release dextromethorphan preparations. For the single-dose study, each of 12
      subjects received 15 mg of immediate-release dextromethorphan in period I and
      period II, respectively, with a 1-week washout period. For the multiple-dose
      study, each of 16 subjects received 60 mg controlled-release dextromethorphan
      twice daily for 5 days in period I and period II, respectively, with a 2-week
      washout period. Dextromethorphan and dextrorphan were assayed by high-performance
      liquid chromatography. In the single-dose study, most metabolic ratios revealed
      good repeatabilities for the two periods (paired t test). The metabolic ratio
      from urine collected for 4 h, 6 h, 8 h or 12 h from plasma at any time between 1
      h and 5 h or at 8 h, or from saliva at 2 h or 6 h, could reflect that from 0- to
      24-h urine or AUCinfinity. In the multiple-dose study, all metabolic ratios
      revealed good repeatabilities. The plasma metabolic ratio at any time between 0.5
      h and 10 h or the saliva metabolic ratio at any time between 3 h and 12 h, but
      not the urine metabolic ratio from any interval, could predict the metabolic
      ratio from ACUSStau. The 2 h, 3 h, 4 h or 5 h plasma metabolic ratio and 6 h
      saliva metabolic ratios after a single dose correlated significantly with their
      corresponding multiple-dose metabolic ratio (r > 0.8, P < .05). In conclusion,
      the plasma sample at 2 h, 3 h, 4 h or 5 h or the saliva sample at 6 h in either
      the single immediate-release (15 mg) or the multiple controlled-release dose (60
      mg) procedure could be used for determining the dextromethorphan metabolic ratio.

PMID- 9618395
TI  - Differential mechanisms in the effects of disulfiram and diethyldithiocarbamate
      intoxication on striatal release and vesicular transport of glutamate.
AB  - Intoxication with the alcohol-aversive drug disulfiram (Antabuse) and related
      dithiocarbamates may provoke neuropathies and, in some cases, damage the basal
      ganglia. Rats received a single administration of disulfiram (7 and 500 mg kg-1
      i.p.) and equimolar doses (4 and 290 mg kg-1 i.p.) of its metabolite
      diethyldithiocarbamate (DDC), roughly corresponding to the daily maximum dose in
      alcohol abusers or to an estimated nonlethal overdose, respectively. The
      striatal, extracellular levels of glutamate in freely moving rats previously
      implanted with a microdialysis probe increased after low and intoxicating doses
      of disulfiram (126 +/- 3% and 154 +/- 10% of basal values, respectively) and DDC
      as well (135 +/- 10% and 215 +/- 14%, respectively), a partially Ca++-dependent
      effect. The prolonged (>7 hr) disulfiram-induced increase in glutamate observed
      in vivo may reflect the in vitro disulfiram-evoked release of glutamate from
      striato-cortical synaptic vesicles, where the drug nonspecifically inhibited (Ki
      approximately 4 microM) the uptake function and abolished the transmembrane
      proton gradient (DeltapH). In contrast, DDC did not seem to affect DeltapH. The
      prompt DDC-provoked increase in extracellular levels of glutamate was prevented
      by 7-nitroindazole, an in vivo specific inhibitor of neuronal nitric oxide
      synthase, which suggests that the thiol metabolite also acts via the nitric oxide
      synthesis. At variance, the short-acting 7-nitroindazole did not prevent the
      sustained in vivo effects of disulfiram and of DDC putatively formed with time.
      These findings provide new evidence for differential mechanisms underlying
      disulfiram- and DDC-induced increases in striatal glutamate release. Present
      glutamatergic changes, although not appearing dramatic enough to represent the
      only cause for neuronal damage from disulfiram overdose, might contribute to the
      drug neurotoxicity.

PMID- 9618396
TI  - Regulation of renin secretion through reversible phosphorylation of myosin by
      myosin light chain kinase and protein phosphatase type 1.
AB  - Possible involvement of reversible phosphorylation and dephosphorylation of
      myosin light chain (MLC) by myosin light chain kinase (MLCK) and protein
      phosphatases (PPases), respectively, in the Ca++-calmodulin-dependent inhibition
      of renin secretion was investigated with the use of putative MLCK inhibitor ML-7
      [1-(5-iodonaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine] and PPase type1
      (PPase-1) and type 2A (PPase-2A) inhibitor calyculin A. ML-7 (1 x 10(-)6 to 3 x
      10(-)5 M) increased renin secretion in vitro from rat renal cortical slices under
      "resting" conditions in a concentration-dependent manner with maximal 2.5-fold
      stimulation. Furthermore, Ca++-induced inhibition of renin secretion in
      depolarizing K+-rich Krebs-Ringer bicarbonate not only was prevented completely
      but also reversed by ML-7 in a concentration-dependent and reversible manner. On
      the other hand, calyculin A (3 x 10(-)6 M) blocked both effects of ML-7 on
      stimulation and reversal of renin secretion independently of intracellular Ca++
      concentrations. Such antagonistic effects of ML-7 and calyculin A on renin
      secretion most likely resulted from their respective effects on the level of MLC
      phosphorylation: ML-7 stimulates renin secretion by decreasing phosphorylation of
      MLC through its inhibition of MLCK, whereas calyculin A inhibits secretion by
      increasing phosphorylation of MLC through its inhibition of PPase-1. By inference
      from these results, MLC may be the target protein involved in regulation of the
      renin secretory process by Ca++: Ca++-calmodulin phosphorylates MLC via
      activating MLCK and thereby inhibits renin secretion, whereas dephosphorylation
      of phosphorylated MLC by PPase-1 reverses the inhibited secretion. We therefore
      conclude that reversible phosphorylation of MLC may be an important biochemical
      step determining the rate of renin secretion from the juxtaglomerular cell.

PMID- 9618397
TI  - Membrane potential-dependent and -independent vasodilation in small pulmonary
      arteries from chronically hypoxic rats.
AB  - Chronic hypoxia is associated with altered pulmonary vasoreactivity, and it has
      been suggested that an increased response to voltage-dependent vasodilators may
      relate to enhanced Ca++ entry via voltage-dependent channels, secondary to
      depolarization. Few studies have been performed on small pulmonary arteries, and
      it is unknown whether they are depolarized after chronic hypoxia. We examined the
      resting membrane potential, and the actions of voltage-dependent (verapamil,
      levcromakalim) and -independent (isoproterenol, forskolin, papaverine)
      vasodilators in small ( approximately 300 microm internal diameter) pulmonary
      arteries from chronically hypoxic rats. The resting membrane potential was more
      positive in arteries after chronic hypoxia (control: -60 +/- 0.5 mV; hypoxic: 
      54.4 +/- 1.1 mV; P < .01), and this was reflected by a shift to the left of the
      response curves for K+ and 4-aminopyridine. In arteries constricted with
      prostaglandin F2alpha the response to verapamil and levcromakalim was increased
      after chronic hypoxia, although maximum prostaglandin F2alpha-induced tension was
      unchanged, which implies a reduction in voltage-independent constrictor
      mechanisms. Although vasorelaxation to isoproterenol was depressed in arteries
      from hypoxic rats, forskolin-induced relaxation was enhanced substantially, and
      because the response to the phosphodiesterase inhibitor papaverine was unchanged,
      we suggest that this reflects an up-regulation of adenylate cyclase. In
      conclusion, chronic hypoxia resulted in a significant depolarization in small
      pulmonary arteries, but this may explain only partly the increased efficacy of
      voltage-dependent vasodilators. Whether the reduction in voltage-independent
      constrictor mechanisms is related to the apparent up-regulation of adenylate
      cyclase remains to be elucidated.

PMID- 9618398
TI  - Trazodone is a potent agonist at 5-HT2C receptors mediating inhibition of the N
      methyl-D-aspartate/nitric oxide/cyclic GMP pathway in rat cerebellum.
AB  - The effects of trazodone on the cyclic GMP elevation elicited by N-methyl-D
      aspartate in rat cerebellar slices were analyzed. Trazodone inhibited in a
      concentration-dependent manner (EC50 = 0.82 nM) the cyclic GMP response evoked by
      0.1 microM N-methyl-D-aspartate. The inhibition was near complete at 10 nM
      trazodone. The effect of 10 nM trazodone was unaffected by 0.3 microM spiperone
      or rauwolscine, antagonists with selectivity for the 5-HT(serotonin)2A or the 5
      HT2B subtype, respectively, but it was totally prevented by 0.01 microM
      mesulergine, a 5-HT2A/5-HT2B/5-HT2C receptor antagonist. Trazodone was potently
      counteracted (IC50 = 2.7 nM) by the selective 5-HT2B/5-HT2C receptor antagonist N
      (1-methyl-5-indolyl)-N-(3-pyridil) urea HCl and, less potently (IC50 = 95 nM), by
      ketanserin, a 5-HT2A/5-HT2C receptor blocker. It is concluded that trazodone
      behaves as a potent full agonist at the 5-HT2C receptor mediating inhibition of
      the cerebellar N-methyl-D-aspartate/nitric oxide/cyclic GMP system.

PMID- 9618399
TI  - The semisynthetic polysaccharide pentosan polysulfate prevents complement
      mediated myocardial injury in the rabbit perfused heart.
AB  - Pentosan polysulfate (PPS) is a highly sulfated semisynthetic polysaccharide
      possessing a higher negative charge density and degree of sulfation than heparin.
      Like other glycosaminoglycans, the structural and chemical properties of PPS
      promote binding of the drug to the endothelium. Glycosaminoglycans, including
      heparin, inhibit complement activation independent of an action on the
      coagulation system. This ability provides a compelling argument for the
      implementation of this class of compounds in experimental models of cellular
      injury mediated by complement. The objective of this study was to examine whether
      PPS could reduce myocardial injury resulting from activation of the complement
      system. We used the rabbit isolated heart perfused with 4% normal human plasma as
      a source of complement. Hemodynamic variables were obtained before addition of
      PPS (0.03 01 mg/ml) and every 10 min after the addition of human plasma. Compared
      with vehicle-treated hearts, left ventricular end-diastolic pressure was improved
      at the conclusion of the 60-min protocol in hearts treated with PPS (58.9 +/-
      13.6 vs. 15. 2 +/- 4.8 mm Hg). Further evidence as to the protective effects of
      PPS was demonstrated by decreased creatine kinase release compared with vehicle
      (86.5 +/- 28.5 U/l vs. 631.0 +/- 124.8 U/l). An enzyme-linked immunosorbent assay
      for the presence of the membrane attack complex in lymph and tissue samples
      demonstrated decreased membrane attack complex formation in PPS-treated hearts,
      which suggests inhibition of complement activation. This conclusion was supported
      further by the ability of PPS to inhibit complement-mediated red blood cell lysis
      in vitro. The results of this study indicate that PPS can reduce tissue injury
      and preserve organ function that otherwise would be compromised during activation
      of the human complement cascade.

PMID- 9618400
TI  - Structure-activity relationships of indole- and pyrrole-derived cannabinoids.
AB  - Early molecular modeling studies with Delta9-tetrahydrocannabinol (Delta9-THC)
      reported that three discrete regions which interact with brain cannabinoid (CB1)
      receptors corresponded to the C-9 position of the cyclohexene ring, the phenolic
      hydroxyl and the carbon side chain at the C3 position. Although the location of
      these attachment points for aminoalkylindoles is less clear, the naphthalene
      ring, the carbonyl group and the morpholinoethyl group have been suggested as
      probable sites. In this study, a series of indole- and pyrrole-derived
      cannabinoids was developed, in which the morpholinoethyl group was replaced with
      another cyclic structure or with a carbon chain that more directly corresponded
      to the side chain of Delta9-THC and were tested for CB1 binding affinity and in a
      battery of in vivo tests, including hypomobility, antinociception, hypothermia
      and catalepsy in mice and discriminative stimulus effects in rats. Receptor
      affinity and potency of these novel cannabinoids were related to the length of
      the carbon chain. Short side chains resulted in inactive compounds, whereas
      chains with 4 to 6 carbons produced optimal in vitro and in vivo activity.
      Pyrrole-derived cannabinoids were consistently less potent than were the
      corresponding indole derivatives and showed pronounced separation of activity, in
      that potencies for hypomobility and antinociception were severalfold higher than
      potencies for hypothermia and ring immobility. These results suggest that,
      whereas the site of the morpholinoethyl group in these cannabinoids seems crucial
      for attachment to CB1 receptors, the exact structural constraints on this part of
      the molecule are not as strict as previously thought.

PMID- 9618401
TI  - Antagonism of an adenosine/ATP receptor in follicular Xenopus oocytes.
AB  - Follicular Xenopus oocytes possess a novel receptor where both adenosine and ATP
      activate a cAMP-dependent, nonrectifying K+-current. Five compounds, alpha,beta
      methylene ATP (alpha, beta-meATP), 8-(p-sulfophenyl)theophylline (8-SPT),
      theophylline, 2, 2'-pyridylisatogen tosylate (PIT) and suramin, were tested as
      antagonists of adenosine- and ATP-activated K+-currents. The descending order of
      activity (pIC50 values) against adenosine responses was: alpha,beta-meATP (6.72)
      = 8-SPT (6.68) > theophylline (5.32) > PIT (4.58), whereas suramin was relatively
      inactive. The blocking actions of alpha,beta-meATP and alkylxanthine compounds
      were reversible with washout, whereas blockade by PIT was irreversible. These
      antagonists showed similar blocking activity against ATP responses, except for
      PIT which was more effective at ATP responses than at adenosine responses. The
      selectivity of antagonists was tested against cAMP-dependent K+-currents evoked
      by forskolin and follicle-stimulating hormone (FSH). 8-SPT and theophylline did
      not inhibit but instead augmented forskolin and FSH responses; this augmentation
      may be caused by inhibition of phosphodiesterase activity inside follicle cells.
      On the other hand, alpha,beta-MeATP and PIT inhibited forskolin and FSH
      responses; both compounds apparently are nonselective antagonists. Thus, only
      alkylxanthine derivatives (8-SPT and theophylline) were selective antagonists of
      the novel adenosine/ATP receptor in Xenopus oocytes, whereas alpha,beta-meATP and
      PIT were nonselective in their blocking actions and suramin was relatively
      inactive.

PMID- 9618402
TI  - Differential contribution of angiotensinergic and cholinergic receptors in the
      hypothalamic paraventricular nucleus to osmotically induced AVP release.
AB  - We studied the involvement of periventricular and hypothalamic angiotensinergic
      and cholinergic pathways in osmotically induced arginine vasopressin (AVP)
      release into the blood. In conscious Wistar rats, i.c.v. injections of 0.2, 0.3
      and 0.6 M hyperosmolar saline (5 microl) resulted in concentration-dependent
      increases in AVP release (5.2 +/- 1.5, 10.6 +/- 2.2 and 18.0 +/- 2.2 pg/ml,
      respectively, vs. 2.0 +/- 0.1 in controls). The two lower saline concentrations
      did not affect arterial blood pressure (non-pressure-associated AVP release),
      whereas 0.6 M saline induced increase in blood pressure (pressure-associated AVP
      release). In the first set of experiments, periventricular angiotensin AT1,
      muscarinic or nicotinic receptors were blocked by i.c.v. administration of
      losartan (10 nmol), atropine (100 nmol) or hexamethonium (100 nmol),
      respectively, before i.c.v. hyperosmolar saline injections. Losartan
      significantly reduced the 0.2 M and 0.3 M, but not the 0.6 M, saline-induced
      increase in AVP release. The 0. 3 M saline-induced AVP release was blocked by
      atropine and hexamethonium, whereas the 0.6 M saline-induced AVP release was
      blocked by atropine only. In the second set of experiments, losartan (4 nmol),
      atropine (200 nmol) or hexamethonium (200 nmol) was injected bilaterally into the
      paraventricular nucleus before i.c.v. hyperosmolar saline injections. Losartan
      reduced 0.3 M and potentiated 0.6 M saline-induced AVP release. On the other
      hand, atropine and hexamethonium significantly reduced both 0.3 and 0.6 M saline
      induced AVP release. We conclude that afferents arising from periventricular
      osmosensitive neurons to the hypothalamic paraventricular nucleus, which are
      involved in non-pressure-associated osmotically induced AVP release, are both
      angiotensinergic and cholinergic, whereas those mediating pressure-associated AVP
      release are cholinergic in nature.

PMID- 9618403
TI  - Interaction of L-arginine analogs with L-arginine uptake in rat renal brush
      border membrane vesicles.
AB  - The dibasic amino acid, L-arginine, is a substrate for both nitric oxide synthase
      (NOS) and arginase and therefore, plays an important role in cell signaling and
      cell growth. We examined the effects of various NOS inhibitors on L-arginine
      transport into rat renal brush border membrane (BBM) vesicles. L-Arginine uptake
      was stimulated in the presence of an inwardly directed Na+ gradient and an
      imposed inside negative potential in BBM but not basolateral membrane vesicles.
      In BBM vesicles, the L-arginine analogs, N-iminoethyl-L-orinithine and Nw
      monomethyl-L-arginine (L-NMMA) were potent inhibitors of L-arginine uptake (IC50
      of 0.48 and 0.82 mM, respectively), while Nw-nitro-L-arginine was less active
      (IC50 = 10 mM) and Nw-nitro-L-arginine methyl ester (L-NAME) was inactive. The
      inhibition of L-arginine transport by L-NMMA was competitive in nature. L-NIO, L
      NMMA as well as L-arginine and L-lysine but not Nw-nitro-L-arginine methyl ester,
      trans-stimulated L-arginine uptake when preloaded into BBM vesicles. The L
      arginine analogs had no effect on the transport of the neutral amino acid, L
      leucine, in the same preparations. The data suggest that in addition to
      inhibiting NOS, the L-arginine analogs, N-iminoethyl-L-orinithine, L-NMMA and to
      a lesser extent L-NA, also inhibit L-arginine transport across the BBM of
      proximal tubules.

PMID- 9618404
TI  - Pharmacological characterization of a simple behavioral response mediated
      selectively by central adenosine A1 receptors, using in vivo and in vitro
      techniques.
AB  - The behavioral profile of a range of adenosine receptor ligands was examined in
      rats using a locomotor activity model. Adenosine receptor agonists, including the
      selective A1 receptor agonist, N6-cyclopentyladenosine (CPA) and the A2A agonist,
      2-[(2-aminoethylamino)carbonylethyl-phenylethylamino]- 5'-ethylcarboxa
      midoadenosine (APEC), reduced spontaneous motor activity in a dose-dependent
      manner. CPA-induced locomotor depression was attenuated by adenosine A1 receptor
      selective antagonists, such as 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), (R)-1
      [(E)-3-(2-phenylpyrazolo[1, 5-a]pyridin-3-yl)-acryloyl]-2-piperidine ethanol
      (FK453), and (R)-1-[(E)-3-(2-phenylpyrazolo[1, 5-a]pyridin-3-yl)-acryloyl]
      piperidin-2-yl acetic acid (FK352), but not by the A2A receptor antagonist, (E)
      1,3-dipropyl-8-(3, 4-dimethoxystyryl)-7-methylxanthine (KF17837). By contrast,
      APEC-induced hypolocomotion was attenuated by KF17837 but not by DPCPX,
      confirming that adenosine A1 and A2A receptor activation mediates locomotor
      output independently. It was found that two peripheral adenosine receptor
      antagonists, 8-(p-sulphophenyl)-1, 3-dipropylxanthine (DPSPX) and 8-(p
      sulphophenyl)-1, 3-dimethylxanthine (8-PST), did not alter CPA-induced
      hypolocomotion. This confirmed that pharmacological reversal of the adenosine A1
      receptor-mediated response involved a central site of drug action. The
      relationship between occupancy of central adenosine A1 receptors and behavioral
      effect was therefore assessed. Regression analysis on log transformed data
      confirmed associations between antagonist affinity for brain [3H]DPCPX binding
      sites and, in order of increasing significance, the equivalent behavioral dose
      (EBD) for reversal of CPA-induced hypolocomotion (r2 = 0.32), the serum
      concentration of drug (r2 = 0.65), and most significantly with the brain
      concentration of drug detected 20 min after administration of the (EBD) (r2 =
      0.95). These data suggest that competition between agonists and antagonists, for
      occupancy of central adenosine A1 receptors, is intrinsic to the pharmacological
      reversal of CPA-induced hypolocomotion. The validity of the model as a simple
      predictive screen for the blood/brain barrier permeability of adenosine A1
      receptor antagonists was thereby confirmed.

PMID- 9618405
TI  - Effect of COX-1 and COX-2 inhibition on induction and maintenance of carrageenan
      evoked thermal hyperalgesia in rats.
AB  - Intrathecal administration of nonsteroidal anti-inflammatory drugs in the rat
      blocks the thermal hyperalgesia induced by tissue injury, which suggests a role
      for spinal cyclooxygenase (COX) products in this facilitated state. Two isozymes
      of the COX enzyme have been reported, COX-1 and COX-2, but the agents thus far
      examined are not isozyme selective. We examined the effects of intrathecally
      (i.t.) or systemically (i.p.) administered S(+)-ibuprofen (a nonselective COX
      inhibitor) or 1-[(4-methysulfonyl)phenyl]-3-tri-fluoromethyl-5-(4-fluorophenyl)
      pyrazole (SC58125; a COX-2 selective inhibitor) on carrageenan-induced thermal
      hyperalgesia (reduced hindpaw-withdrawal latency). The following observations
      were made: 1) Thermal hyperalgesia otherwise observed during the first 170 min
      was blocked in a dose-dependent manner by S(+)-ibuprofen or SC58125 administered
      i.t. or i.p. before carrageenan treatment. 2) Intraperitoneal, but not i.t.,
      administration of either inhibitor after the establishment of hyperalgesia (170
      min after carrageenan injection) reversed thermal hyperalgesia in a dose
      dependent manner. Thus, the initial component of thermal hyperalgesia after
      tissue injury was blocked by systemic or spinal administration of both COX
      inhibitors, whereas established hyperalgesia was reversed only by systemic
      inhibitors. This study demonstrates that at least spinal COX-2, if not both COX-1
      and COX-2, are necessary for the initiation of thermal hyperalgesia, whereas
      nonspinal sources of prostanoids (synthesized by COX-2 and perhaps also COX-1)
      are important for the maintenance of thermal hyperalgesia associated with tissue
      injury and inflammation.

PMID- 9618406
TI  - Role of extracellular thiols in accumulation and distribution of inorganic
      mercury in rat renal proximal and distal tubular cells.
AB  - Distribution of inorganic mercury (Hg) into both acid-soluble and protein-bound
      fractions of proximal tubular (PT) cells from the rat increased with increasing
      concentrations of Hg up to 10 microM. Little correlation was found between
      subcellular distribution of Hg and dose in distal tubular (DT) cells. Cellular
      accumulation of Hg was rapid, reaching equilibrium values by 10 to 15 min.
      Cellular content of Hg was significantly higher in PT cells than in DT cells at 1
      microM Hg. To assess the effect of extracellular thiols on the intracellular
      accumulation of Hg, PT and DT cells were coincubated with Hg and cysteine,
      glutathione (GSH), bovine serum albumin (BSA) or 2,3-dimercapto-1-propanesulfonic
      acid (DMPS) in a 4:1 thiol:Hg molar ratio. Coexposure with Hg and cysteine
      increased intracellular accumulation of Hg in PT cells at 0.1 microM Hg relative
      to exposure to Hg alone, consistent with an Hg-cysteine conjugate being a
      transport form of Hg. In contrast, coexposure with Hg and BSA or DMPS markedly
      decreased accumulation of Hg relative to cells exposed to Hg alone in both cell
      types. Coexposure with Hg and GSH also decreased accumulation of Hg relative to
      exposure to Hg alone, but the decrease was less than coexposure with either BSA
      or DMPS, suggesting that either an Hg-GSH complex may be a transport form or that
      some of the Hg-GSH complexes were degraded to Hg-cysteine by the action of brush
      border membrane enzymes. These results demonstrate that extracellular thiols
      markedly alter the renal accumulation of Hg and suggest that some Hg-thiol
      conjugates may be important physiological transport forms of Hg in the kidney.

PMID- 9618407
TI  - Toxin and subunit specificity of blocking affinity of three peptide toxins for
      heteromultimeric, voltage-gated potassium channels expressed in Xenopus oocytes.
AB  - The ability of voltage-gated potassium channel alpha-subunits to form
      heteromultimers has complicated efforts to use toxins to characterize potassium
      channels in native cells. Here I investigate the effects of subunit composition
      on toxin blocking affinity, using three members of the Shaker subfamily of
      potassium channel alpha-subunits (Kv1.1, Kv1.2 and Kv1.4), which are known to
      form heteromultimers in vivo, in the Xenopus oocyte expression system. These
      subunits were coexpressed as pairs in which one member was toxin-sensitive and
      the other relatively insensitive. The blocking affinity of two dendrotoxins (DTX
      I and delta-DTX) and a scorpion toxin (tityustoxin-Kalpha) on the resulting mixed
      population of channels was measured to evaluate three models of toxin block. The
      single subunit model, in which a single toxin-sensitive subunit renders the
      channel toxin sensitive, best described all of the data for the two dendrotoxins
      and the block of tityustoxin-Kalpha for a mixed population of channels composed
      of Kv1.1 and Kv1.2 subunits. However, with tityustoxin-Kalpha, the data for a
      mixed population of Kv1.2 and Kv1.4 subunits was fit best by a model in which the
      toxin interacts with all four subunits for high-affinity block. The data suggest
      that subunit composition of potassium channels can have a large effect on toxin
      block and that different toxins yield strikingly diverse results with the same
      pair of subunits, even when they are nearly identical in blocking affinity for
      the toxin-sensitive subunit.

PMID- 9618408
TI  - Effects of trimetazidine on lipid peroxidation and phosphorus metabolites during
      cold storage and reperfusion of isolated perfused rat kidneys.
AB  - This study was undertaken to evaluate the effect of trimetazidine (TMZ) during
      cold storage (CS) and the consequence during normothermic reperfusion in an
      isolated perfused rat kidney model (IPK). IPK was used to assess the rate of
      perfusion flow, the ratio of ATP to inorganic phosphate (ATP/Pi) as a reflection
      of the energetic status during reperfusion, intracellular pH (pHi), tissue water
      content and malondialdehyde (MDA) tissue levels in four different preservation
      solutions after 48-hr preservation at 4 degreesC and 2-hr reperfusion at 37.5
      degreesC: EuroCollins (EC), University of Wisconsin (UW), EC plus TMZ (10(-)6 M)
      (EC + TMZ) and UW plus TMZ (10(-)6 M) (UW + TMZ). When TMZ was added to the
      preservation solutions, perfusion flow rate (PFR) was significantly improved
      during reperfusion. Tissue water content, which reflected tissue edema, was
      significantly lower in TMZ groups than in groups without TMZ during both CS and
      reperfusion conditions. In TMZ groups, ATP/Pi ratio was also significantly
      improved during CS and reperfusion. In addition, TMZ lowered the pHi both during
      preservation and after reperfusion. MDA renal tissue level significantly
      decreased with TMZ both during the preservation period and after reperfusion.
      These overall results strongly suggested that TMZ contributes to renal protection
      from cold ischemia-reperfusion injury in this IPK model, especially when TMZ was
      added to UW solution and during prolonged hypothermic ischemia.

PMID- 9618409
TI  - Effects of gonadal steroids on ventricular repolarization and on the response to
      E4031.
AB  - Gonadal steroids are thought to be important determinants of gender-related
      differences in electrophysiology, such as the longer rate-corrected QTc intervals
      in women and the incidences of some clinical arrhythmias. We studied the chronic
      effects of gonadal steroids on cardiac action potentials (APs) using standard
      electrophysiological techniques. Papillary muscles were removed from the hearts
      of oophorectomized rabbits that had been treated with placebo, estradiol or
      dihydrotestosterone (DHT). The electrocardiograms of the three groups did not
      differ. Papillary muscle APs were studied during drive at cycle lengths of 330 to
      5000 msec. The APD30 of the DHT group was significantly shorter than that of the
      others at cycle lengths of >500 msec. The APD90 of the estradiol group was
      significantly longer than that of the DHT group at cycle lengths of >1000 msec.
      The APD90 of the placebo group tended to be intermediate. The effects of the
      antiarrhythmic drug E4031 (10(-8)-10(-6) M) also were examined. E4031-induced
      prolongation of APD90 and magnitude of early afterdepolarizations was
      significantly greater in the estradiol-treated than the DHT-treated and placebo
      groups. In conclusion, in rabbit heart, gonadal steroids are important
      determinants of base-line electrophysiological properties and the proarrhythmic
      response to E4031.

PMID- 9618410
TI  - Compensatory sleep responses to wakefulness induced by the dopamine autoreceptor
      antagonist (-)DS121.
AB  - The effect of the dopamine autoreceptor antagonist (-)DS121 on wakefulness,
      locomotor activity, body temperature and subsequent compensatory sleep responses
      was examined in the rat. Animals entrained to a light-dark cycle were treated at
      5 h after lights-on (CT-5) with 0.5, 1, 5 or 10 mg/kg i.p. (-)DS121 or
      methylcellulose vehicle. An additional group received 5 mg/kg i.p. (-)DS121 or
      vehicle 6 h after lights-off (CT-18). At CT-5, (-)DS121 dose-dependently
      increased wakefulness, locomotor activity and body temperature, and decreased
      both non-rapid eye movement sleep (NREM) and rapid eye movement sleep (REM)
      during the first 4 h post-treatment relative to vehicle controls. REM
      interference lasted up to 3 h longer than NREM. Low doses of (-)DS121 (0.5 and 1
      mg/kg) produced relatively little waking that was not followed by significant
      compensatory sleep responses. In contrast, higher doses (5 and 10 mg/kg) produced
      compensatory hypersomnolence (robust increases in NREM immediately after the
      primary waking effect) that was proportional to the duration of drug-induced
      wakefulness. NREM recovery 24 h post-treatment was the same for the 5 mg/kg (65.4
      +/- 9.9 min) and 10 mg/kg (64.8 +/- 9.3 min) doses, but was not proportional to
      prior wake duration. NREM displaced by drug-induced wakefulness was recovered
      completely by 24 h post-treatment at the 5 mg/kg dose, but only 63.5% recovered
      at 10 mg/kg. In contrast, equivalent wakefulness produced by sleep deprivation
      yielded 100% NREM recovery. At CT-18, (-)DS121 (5 mg/kg) increased wakefulness
      without disproportionately increasing locomotor activity, and was compensated
      fully by 24 h post-treatment. These data show that (-)DS121 dose-dependently
      increases wakefulness, which is followed by hypersomnolence that is proportional
      to drug-induced wake-promoting efficacy.

PMID- 9618411
TI  - The contribution of classical (beta1/2-) and atypical beta-adrenoceptors to the
      stimulation of human white adipocyte lipolysis and right atrial appendage
      contraction by novel beta3-adrenoceptor agonists of differing selectivities.
AB  - The role of beta3- and other putative atypical beta-adrenoceptors in human white
      adipocytes and right atrial appendage has been investigated using CGP 12177 and
      novel phenylethanolamine and aryloxypropanolamine beta3-adrenoceptor (beta3AR)
      agonists with varying intrinsic activities and selectivities for human cloned
      betaAR subtypes. The ability to demonstrate beta1/2AR antagonist-insensitive
      (beta3 or other atypical betaAR-mediated) responses to CGP 12177 was critically
      dependent on the albumin batch used to prepare and incubate the adipocytes. Four
      aryloxypropanolamine selective beta3AR agonists (SB-226552, SB-229432, SB-236923,
      SB-246982) consistently elicited beta1/2AR antagonist-insensitive lipolysis.
      However, a phenylethanolamine (SB-220646) that was a selective full beta3AR
      agonist elicited full lipolytic and inotropic responses that were sensitive to
      beta1/2AR antagonism, despite it having very low efficacies at cloned beta1- and
      beta2ARs. A component of the response to another phenylethanolamine selective
      beta3AR agonist (SB-215691) was insensitive to beta1/2AR antagonism in some
      experiments. Because no [corrected] novel aryloxypropanolamine had a beta1/2AR
      antagonist-insensitive inotropic effect, these results establish more firmly that
      beta3ARs mediate lipolysis in human white adipocytes, and suggest that putative
      'beta4ARs' mediate inotropic responses to CGP 12177. The results also illustrate
      the difficulty of predicting from studies on cloned betaARs which betaARs will
      mediate responses to agonists in tissues that have a high number of beta1- and
      beta2ARs or a low number of beta3ARs.

PMID- 9618412
TI  - Activation of human liver 3alpha-hydroxysteroid dehydrogenase by clofibrate
      derivatives.
AB  - The NADP+-dependent dehydrogenase activity of a predominant isoenzyme of human
      liver 3alpha-hydroxysteroid dehydrogenase was activated by antihyperlipidemic
      drugs, such as bezafibrate and clinofibrate, and by clofibric acid and fenofibric
      acid (active metabolites of clofibrate and fenofibrate, respectively). The
      optimal pH of the activation by the drugs was about 7.5, and the concentrations
      giving maximum stimulation (1.8- to 2.4-fold) were 100, 50, 400 and 50 microM for
      bezafibrate, clinofibrate, clofibric acid and fenofibric acid, respectively.
      Clofibrate and fenofibrate acted as weak inhibitors, and the clofibric acid
      derivatives that lack the chloro group, methyl group on the alpha-carbon or
      carboxyl group greatly decreased the stimulatory effects. The activation by the
      drugs increased both Km and kcat (turnover number) values for the coenzyme and
      substrates. Kinetic analysis with respect to NADP+ showed that bezafibrate,
      clinofibrate, clofibric acid and fenofibric acid were nonessential activators
      showing dissociation constants of 32, 6, 103 and 11 microM, respectively. The
      combined activators experiments with one of the above drugs and
      sulfobromophthalein, a known activator specific for this enzyme, and comparison
      of their effects on the activities of mutant enzymes (with Met replacing Lys-270
      or Arg-276) indicated that sulfobromophthalein and the drugs bind to an identical
      site on the enzyme. These results suggest that the long-term therapy with the
      antihyperlipidemic drugs influences the metabolism of steroid hormones, bile
      acids and several ketone-containing drugs mediated by the enzyme.

PMID- 9618413
TI  - Metabolism and transport of the macrolide immunosuppressant sirolimus in the
      small intestine.
AB  - Small intestinal metabolism and transport of sirolimus, a macrolide
      immunosuppressant with a low and highly variable oral bioavailability, were
      investigated using small intestinal microsomes and intestinal mucosa in the
      Ussing chamber. After incubation of sirolimus with human and pig small intestinal
      microsomes, five metabolites were detected using high performance liquid
      chromatography/electrospray-mass spectrometry: hydroxy, dihydroxy, trihydroxy,
      desmethyl and didesmethyl sirolimus. The same metabolites were generated by human
      liver microsomes and pig small intestinal mucosa in the Ussing chamber. Anti
      CYP3A antibodies, as well as the specific CYP3A inhibitors troleandomycin and
      erythromycin, inhibited small intestinal metabolism of sirolimus, confirming
      that, as in the liver, CYP3A enzymes are responsible for sirolimus metabolism in
      the small intestine. Of 32 drugs tested, only known CYP3A substrates inhibited
      sirolimus intestinal metabolism with inhibitor constants (Ki) equal to those in
      human liver microsomes. The formation of hydroxy sirolimus by small intestinal
      microsomes isolated from 14 different patients ranged from 28 to 220 pmol.min
      1.mg-1 microsomal protein. In the Ussing chamber, >99% of the sirolimus
      metabolites reentered the mucosa chamber against a sirolimus gradient, indicating
      active countertransport. Intestinal drug metabolism and countertransport into the
      gut lumen, drug interactions with CYP3A substrates and inhibitors in the small
      intestine and an 8-fold interindividual variability of the intestinal metabolite
      formation rate significantly contribute to the low and highly variable
      bioavailability of sirolimus.

PMID- 9618414
TI  - Pharmacodynamics of a monoclonal antiphencyclidine Fab with broad selectivity for
      phencyclidine-like drugs.
AB  - The development of treatment strategies for drug intoxication has been hindered
      in part by the lack of clinically useful antagonists. Consequently, the major
      goal of these studies was to determine whether a monoclonal antibody Fab fragment
      (of IgG) could be used as an effective drug class-selective antagonist and to
      understand better the dose-response relationships for reversing CNS drug
      toxicity. Changes in drug-induced locomotor effects in a rat model were used to
      assess the ability of the antiphencyclidine (anti-PCP) Fab to reverse the
      behavioral effects of PCP and other potent arylcyclohexylamines. In experiments
      to determine the pharmacodynamics of Fabinduced antagonism of behavioral effects,
      the Fab completely reversed all PCP-induced locomotor effects in a Fab dose
      dependent manner with a minimal effective dose of 0.18 mole-equivalents of Fab
      and an ED50 value of about one-third mole-equivalent. The anti-PCP Fab also
      completely reversed the locomotor effects induced by two other structurally
      related potent analogs of PCP: 1-[1-(2-thienyl)cyclohexyl]piperidine and N-ethyl
      1-phenylcyclohexylamine. In addition, pharmacological and immunological
      selectivity was further tested by treatment of the behavioral effects induced by
      the structurally unrelated locomotor stimulant (+)methamphetamine. The antibody
      did not effectively reverse the effects of methamphetamine-induced locomotor
      activity. These results indicate that antibody-based medications can be developed
      to treat toxicity caused by classes of drugs as well as by individual drugs.

PMID- 9618415
TI  - Discriminative stimulus effects of a cocaine/heroin "speedball" combination in
      rhesus monkeys.
AB  - Cocaine and heroin often are abused together in a combination known as a
      "speedball," but relatively little is known about ways in which cocaine and
      heroin may interact to modify each other's abuse-related effects. The present
      study evaluated the discriminative stimulus effects of a speedball combination of
      cocaine and heroin. Three rhesus monkeys were trained to discriminate vehicle
      from a 10:1 ratio of cocaine (0.4 mg/kg) in combination with heroin (0.04 mg/kg).
      Both cocaine alone and heroin alone substituted completely for the cocaine/heroin
      combination, although cocaine and heroin were more potent when administered
      together than when administered alone. Combined pretreatment with the dopamine
      antagonist flupenthixol and the opioid antagonist quadazocine dose-dependently
      antagonized the discriminative stimulus effects of the cocaine/heroin
      combination, but pretreatment with either antagonist alone was less effective.
      These findings suggest that either cocaine or heroin alone was sufficient to
      substitute for the cocaine/heroin training combination. To characterize the
      discriminative stimulus properties of this speedball more fully, a series of
      cocaine-like and heroin-like agonists were studied in substitution tests. The
      indirect dopamine agonists CFT, amphetamine and bupropion and the mu opioid
      agonists alfentanil, fentanyl and morphine produced high levels of speedball
      appropriate responding. However, the indirect dopamine agonist GBR12909, the D1
      dopamine agonist SKF82958, the D2 dopamine agonist quinpirole and the partial mu
      opioid agonist nalbuphine did not substitute for the cocaine/heroin combination.
      Because these compounds produce discriminative stimulus effects similar to either
      cocaine or mu opioid agonists alone, these findings suggest that the
      discriminative stimulus effects of the cocaine/heroin combination do not overlap
      completely with the effects of cocaine and heroin alone. Finally, a series of
      compounds that produce partial or no substitution for cocaine or mu agonists
      alone also did not substitute for the cocaine/heroin combination, which indicates
      that the discriminative stimulus effects of the combination were
      pharmacologically selective. Taken together, these findings suggest that a
      combination of cocaine and heroin produces a pharmacologically selective
      discriminative stimulus complex that includes aspects of both component drugs.

PMID- 9618416
TI  - Anticonvulsant drug effects in the direct cortical ramp-stimulation model in
      rats: comparison with conventional seizure models.
AB  - A modified cortical ramp stimulation (CRS) model has been developed allowing
      repeated determinations of seizure threshold at short time intervals in
      individual rats without inducing postictal threshold increases. Anticonvulsant
      potency of the standard antiepileptic drugs carbamazepine, phenytoin,
      phenobarbital, valproate, diazepam and ethosuximide in the CRS model was compared
      with respective drug potencies in two more traditional seizure models with
      transcorneal stimulus application, i.e., the minimal electroshock seizure
      threshold (minEST) and the maximal electroshock seizure threshold (maxEST). In
      the CRS model, two different types of threshold were determined, the threshold
      for localized seizures (TLS) and the threshold for generalized seizures (TGS).
      When screw electrodes were implanted over the primary motor cortex, TLS was
      characterized by unilateral forelimb clonus, tonic abduction of contralateral
      forelimb, and head adversion. When ramp-shaped stimulation was continued above
      the TLS current, bilateral clonic forelimb seizures with loss of posture
      developed, which was defined as TGS. In contrast to TLS, TGS could not be
      repeatedly determined at short time intervals because of postictal threshold
      increase. TLS was dose-dependently increased by carbamazepine, phenobarbital,
      valproate and diazepam, although phenytoin showed a truncated dose-response, and
      ethosuximide was ineffective. In comparison to TLS, drug-induced increases in TGS
      were more marked. All drugs dose-dependently increased minEST and, except
      ethosuximide, maxEST. For comparison of drug potencies, doses increasing seizure
      thresholds by 20 or 50% were calculated from dose-response curves. Respective
      comparisons showed marked differences in drug potencies between models,
      indicating that the CRS method presents a model of another, more
      pharmacoresistant seizure type than seizure types induced in traditional models,
      such as transcorneal electroshock. Based on the location of electrodes in the
      frontal neocortex, the characteristic seizure pattern, and the low
      pharmacological sensitivity of the seizures to standard antiepileptics, the
      modified CRS model most likely represents a new model of localization-related
      seizures occurring in frontal lobe epilepsy and may thus be used in the search
      for novel drugs with higher efficacy against this difficult-to-treat type of
      epilepsy.

PMID- 9618417
TI  - CB1 receptor antagonist precipitates withdrawal in mice exposed to Delta9
      tetrahydrocannabinol.
AB  - Although tolerance to cannabinoids has been well established, the question of
      cannabinoid dependence had been very controversial until the discovery of a
      cannabinoid antagonist, SR141716A. The objective of this study was to develop and
      characterize a mouse model of precipitated withdrawal indicative of cannabinoid
      dependence. Using a dosing regimen known to produce pharmacological and
      behavioral tolerance, mice were treated with Delta9-tetrahydrocannabinol (Delta9
      THC) twice a day for 1 wk. SR141716A administration after the last Delta9-THC
      injection promptly precipitated a profound withdrawal syndrome. Typical
      withdrawal behavior was an increase in paw tremors and head shakes that was
      accompanied with a decrease in normal behavior such as grooming and scratching.
      Of the three Delta9-THC regimens tested, daily Delta9-THC injections of 10 and 30
      mg/kg produced the greatest number of paw tremors and head shakes and the least
      number of grooms after challenge with SR141716A. Precipitated withdrawal was
      apparent after 2, 3, 7 and 14 days of treatment based on an increase in paw
      tremors in Delta9-THC-treated mice as compared with vehicle-treated mice. These
      findings are consistent with SR141716A-precipitated withdrawal in rats. Moreover,
      these results suggest that mice are a viable model for investigating dependence
      to cannabinoids.

PMID- 9618418
TI  - The excitatory behavioral and antianalgesic pharmacology of normorphine-3
      glucuronide after intracerebroventricular administration to rats.
AB  - In the adult male Sprague-Dawley rat, a species commonly used to study tolerance
      to the antinociceptive effects of morphine, approximately 10% of the morphine
      dose is metabolized to normorphine-3-glucuronide (NM3G). In contrast, NM3G is a
      relatively minor metabolite of morphine in human urine reportedly accounting for
      approximately 1% of the morphine dose. To date, the pharmacology of NM3G has been
      poorly characterized. Therefore, our studies were designed to determine whether
      the intrinsic pharmacology of NM3G is similar to that of morphine-3-glucuronide
      (M3G), the major metabolite of morphine, which has been shown to be a potent
      central nervous system (CNS) excitant and to attenuate the intrinsic
      antinociceptive effects of morphine in rats. The CNS excitatory potency of NM3G
      was found to be approximately half that of M3G, inducing convulsions in rats at
      intracerebroventricular (i.c.v.) doses of >/=16.8 nmol. When administered before
      morphine (70 nmol i. c.v.), NM3G (8.9 nmol i.c.v.) attenuated antinociception for
      up to 2 hr, but when administered after morphine, no significant attenuation of
      morphine antinociception was observed. Thus, after i.c.v. administration, NM3G
      like M3G, is a potent CNS excitant and antianalgesic in the rat. NM3G may
      therefore play a role in the development of tolerance to the antinociceptive
      effects of morphine in the rat as has been proposed previously for M3G.

PMID- 9618419
TI  - Drug discrimination in methamphetamine-trained monkeys: agonist and antagonist
      effects of dopaminergic drugs.
AB  - The involvement of D1 and D2 subtypes of dopamine receptors in behavioral effects
      of methamphetamine was studied in squirrel monkeys using a two-lever drug
      discrimination procedure. In monkeys that discriminated i.m. injections of 0.3
      mg/kg methamphetamine from saline, methamphetamine (0.03-0.3 mg/kg), cocaine (0.1
      1.0 mg/kg) and the selective dopamine uptake inhibitor, GBR 12909 (3.0-17.8
      mg/kg) produced dose-related increases in responding on the methamphetamine
      associated lever and, at the highest doses, full substitution. In contrast, the
      norepinephrine and serotonin uptake inhibitors, tomoxetine (1.0-17.8 mg/kg) and
      fluoxetine (0.3-10.0 mg/kg), respectively, did not substitute appreciably for
      methamphetamine. Substitution for methamphetamine also was observed with the D1
      receptor agonists, SKF 81297, SKF 82958 and dihydrexidine, and the D2 receptor
      agonist, (+)-PHNO in the majority of monkeys. Lower-efficacy D1 or D2 agonists
      substituted for methamphetamine either partially (SDZ 208-911) or not at all (SKF
      77434, SDZ 208-912). Pretreatment with dopamine receptor blockers [D1 (SCH 39166,
      0.1 mg/kg) or D2 (remoxipride, 3.0 mg/kg and nemonapride, 0.003 mg/kg)] and low
      efficacy agonists [D1 (SKF 77434; 3.0 mg/kg) or D2 (SDZ 208-911 and SDZ 208-912;
      0.01-0.03 mg/kg)] antagonized the discriminative-stimulus effects of
      methamphetamine. In separate studies, comparable doses of each of these drugs,
      except SKF 77434, induced significant levels of catalepsy-associated behavior.
      These results support the view that both dopaminergic D1 and D2 mechanisms
      mediate the discriminative-stimulus effects of methamphetamine; further, they
      indicate that selected dopamine D1 partial agonists may have antagonist actions
      at doses that do not produce undesirable effects associated with dopamine
      receptor blockade.

PMID- 9618420
TI  - A new interpretation of salicylic acid transport across the lipid bilayer:
      implications of pH-dependent but not carrier-mediated absorption from the
      gastrointestinal tract.
AB  - Transport of several monocarboxylic acids across the lipid bilayer was examined
      in liposomes consisting of egg yolk phosphatidylcholine and cholesterol. In the
      presence of inward proton gradient, salicylic acid (SA) was taken up rapidly by
      liposomes showing overshoot, saturation and competitive inhibition phenomena.
      These carrier-mediated like profiles of SA uptake can be explained by assuming a
      very high permeability through the liposomal membrane of protonated SA.
      Protonated SA in the extraliposomal solution (pH 5.8) was taken up by liposomes
      rapidly, followed by a redissociation to anion according to the intraliposomal pH
      (pH 7.5). The concentration gradient of protonated SA across the liposomal
      membrane is maintained until the intraliposomal pH decreased to the
      extraliposomal level, which facilitates the uptake of SA into liposomes. The
      permeability of the lipid bilayer to several compounds was estimated from the
      inhibitory effects of those compounds on SA uptake by liposomes. Good linear
      relationships were observed between their inhibitory effects on the liposomal
      uptake of SA and the permeability of the intestinal membrane to them determined
      both in vivo and in vitro. These results clearly indicate that the carrier
      independent transport mechanism of monocarboxylic acids observed in liposomes
      significantly contributes to their absorption from the intestinal tract under
      physiological conditions.

PMID- 9618421
TI  - Delta opioid receptor enhancement of mu opioid receptor-induced antinociception
      in spinal cord.
AB  - Although the mu selective agonist [D-Ala2-MePhe4-Gly-ol5]enkephalin (DAMGO) and
      the delta selective agonist [D-Pen2,D-Pen5]enkephalin (DPDPE) are both
      antinociceptive when administered directly into the spinal cord of mice, 50% of
      antinociceptive dose (AD50) of DAMGO is about 2 orders of magnitude lower than
      the AD50 of DPDPE. In contrast, the two ligands show similar affinities for their
      respective receptors in in vitro binding assays. One possible explanation for
      this discrepancy is that DPDPE antinociception in the spinal cord is mediated
      through not delta but mu receptors, for which it has an several hundred-fold
      lower affinity than DAMGO. In support of this, we found that DPDPE-mediated
      antinociception was blocked by the mu selective antagonist D-Phe-Cys-Tyr-D-Trp
      Arg-Thr-Pen-Thr-NH2 (CTAP). The pA2 value of CTAP for DPDPE was virtually
      identical with that for DAMGO. However, because its action also was blocked by
      naltrindole, an antagonist selective for delta receptors, the latter must also
      play a role in antinociception. When DAMGO and DPDPE were administered i.t.
      together at ratios ranging from 1:200 to 1:500, the AD50 of DAMGO was lowered as
      much as 10-fold relative to its AD50 when given alone. Thus DPDPE had a
      potentiating effect on DAMGO, although the reverse was not observed. This
      potentiation was lost in animals made tolerant to systemic morphine. The loss of
      potentiation seemed to be caused by changes in the delta receptors, because a)
      the AD50 of DAMGO (i.t.) given alone to tolerant animals was virtually the same
      as for naive animals, whereas the AD50 of DPDPE given alone increased by 4-fold;
      and b) the AD50 of DPDPE given alone in the tolerant animal was increased only
      slightly by naltrindole, whereas CTAP was still a very potent antagonist. We
      conclude that DPDPE, a selective delta agonist, mediates antinociception in the
      spinal cord through mu receptors, consistent with results of recent studies of
      "knock-out" mice lacking mu receptors. At the same time, however, the delta
      agonist acting through delta receptors can potentiate the mu receptor-mediated
      antinociceptive action of either mu or delta agonists. This potentiating effect,
      like the synergistic effect observed between mu receptors at spinal and
      supraspinal sites, is lost during tolerance.

PMID- 9618422
TI  - D2 dopamine antisense RNA expression vector, unlike haloperidol, produces long
      term inhibition of D2 dopamine-mediated behaviors without causing Up-regulation
      of D2 dopamine receptors.
AB  - Long-term inhibition of D2 dopamine receptors using classic D2 dopamine receptor
      antagonists such as haloperidol often causes a compensatory up-regulation of the
      D2 dopamine receptors. We investigated whether the long-term inhibition of D2
      dopamine receptors using an eukaryotic expression vector housing a cDNA sequence
      encoding an antisense RNA directed to the D2 dopamine receptor transcript (D2
      antisense vector) would also produce up-regulation of the D2 receptors. Single,
      bilateral injections of the D2 antisense vector into the corpora striata of mice
      inhibited the stereotypy induced by acute challenge injections with the D2/D3
      dopamine receptor agonist quinpirole but did not inhibit the grooming induced by
      acute challenge injections with the D1 agonist SKF 38393. Similar treatment with
      the D2 antisense vector produced a long-term (>1 month) cataleptic response
      without producing tolerance to challenge injections with haloperidol. By
      contrast, catalepsy induced by a single injection of haloperidol lasted only
      approximately 2 days, and tolerance developed to its effects after long-term
      treatment. Repeated treatment of mice with haloperidol resulted in an inhibition
      of apomorphine-induced climbing behavior throughout the time of treatment with
      haloperidol, but the climbing behavior markedly increased to levels significantly
      higher than that of the control mice immediately after withdrawal from
      haloperidol treatment. This increased climbing was accompanied by increased
      levels of D2 dopamine receptors in the striatum. By contrast, single, bilateral
      intrastriatal injections of the D2 antisense vector significantly inhibited
      apomorphine-induced climbing for approximately 30 days but failed to increase the
      climbing behavior or the levels of D2 dopamine receptors in striatum over those
      of the control values. These results suggest that a single injection of a D2
      antisense RNA expression vector into mouse striatum produces specific, long-term
      inhibition of D2 dopamine receptor behaviors without causing a compensatory
      increase in the levels or function of D2 dopamine receptors.

PMID- 9618423
TI  - Clocinnamox antagonism of the antinociceptive effects of mu opioids in squirrel
      monkeys.
AB  - The opioid agonists morphine, etorphine, buprenorphine and U50,488 were examined
      alone and in combination with the insurmountable opioid antagonist clocinnamox (C
      CAM) in squirrel monkeys responding under a schedule of shock titration. In this
      procedure, shock intensity increased every 15 sec from 0.01 to 2.0 mA in 30
      increments. Five lever presses during any given 15-sec shock period produced a 15
      sec timeout, after which shock resumed at the next lower intensity. When given
      alone, each of these agonists increased the median intensity at which the monkeys
      maintained shock [median shock level (MSL)]. At the highest dose examined alone,
      each agonist produced maximal increases in MSL and, except buprenorphine,
      decreased response rates. C-CAM dose-dependently antagonized the effects of
      morphine, etorphine and buprenorphine on MSL. In the presence of the higher C-CAM
      doses, etorphine, morphine and buprenorphine did not produce maximal effects on
      MSL. The effects of U50,488 were not systematically altered when tested in
      combination with the highest C-CAM dose. In general, C-CAM was more potent and
      the duration of antagonism was slightly longer against buprenorphine than against
      morphine and etorphine. Quantitative analysis of these data according to an
      extended model of yielded the following apparent affinity and efficacy estimates,
      respectively: etorphine (0. 085 mg/kg, 117); morphine (49 mg/kg, 24) and
      buprenorphine (0.62 mg/kg, 7.1). Determination of the individual q values over
      time indicated that the receptor population recovers more quickly after C-CAM
      antagonism of etorphine than from C-CAM antagonism of either morphine or
      buprenorphine. These data suggest that C-CAM functions as a long-lasting
      antagonist of mu opioid agonist actions in a shock titration procedure and yields
      estimates of relative intrinsic efficacy with the rank order of etorphine >
      morphine > buprenorphine.

PMID- 9618424
TI  - Fentanyl and its analogs desensitize the cloned mu opioid receptor.
AB  - Fentanyl, and its structural analogs lofentanil and sufentanil, are potent
      analgesics used clinically in the management of pain. However, the high analgesic
      potency of these compounds is limited by the development of tolerance after
      chronic use. To investigate whether their tolerance development may be related to
      mu receptor desensitization, the cloned mouse mu receptor as well as mutant forms
      of the receptor were stably expressed in HEK 293 cells and tested for their
      response to continuous opioid treatment. Fentanyl and its analogs potently bound
      to the mu receptor and effectively inhibited cAMP accumulation. Three-hour
      pretreatment of mu receptors with fentanyl and its analogs desensitized the mu
      receptor by uncoupling it from adenylyl cyclase. The fentanyl analogs caused a
      slight internalization of the mu receptor as accessed by antibody binding to the
      epitope-tagged mu receptor. Truncation of the mu receptor by removal of its
      carboxyl terminus at Glu341 did not affect the ability of the fentanyl analogs to
      bind to and activate the mu receptor nor did it prevent the fentanyl analogs from
      desensitizing the receptor. In a previous study we showed that morphine did not
      desensitize the cloned mu receptor even though it is a potent and effective
      agonist at the mu receptor. Mutagenesis studies revealed that morphine interacts
      differently with the mu receptor to activate it than do the fentanyl analogs
      which may explain its lack of desensitization of the mu receptor. These results
      indicate that desensitization of the mu receptor may be a molecular basis for the
      development of tolerance to fentanyl and its analogs.

PMID- 9618425
TI  - Serotonergic modulation of acetylcholine release from cortex of freely moving
      rats.
AB  - The modulation of acetylcholine (ACh) release by 5-HT3 receptor activation was
      studied using in vivo microdialysis. Spontaneous and K+-stimulated ACh release
      were measured in frontoparietal cortex and hippocampus of freely moving rats. Two
      consecutive exposures to high K+ produced ACh release of similar magnitude. In
      the cortex, serotonin (5-HT) failed to alter spontaneous ACh release, but caused
      a concentration-dependent decrease of K+-evoked ACh release. Phenylbiguanide
      (PBG) and m-chlorophenylbiguanide, two selective 5-HT3 agonists, mimicked the 5
      HT responses, but 8-hydroxy-2-(di-n-propylamino)tetralin, a selective 5-HT1A
      agonist, was without effect. However, PBG failed to modify K+-evoked ACh release
      from the hippocampus. Systemic and local administration of a highly selective 5
      HT3 antagonist, tropisetron ((3-alpha-tropanyl)1H-indole-carboxylic acid ester)
      blocked the effect of both 5-HT and PBG. The inhibition of ACh release by PBG was
      sensitive to tetrodotoxin. These observations provide direct evidence that, in
      rat cortex, 5-HT modulates in-vivo release of ACh through activation of 5-HT3
      receptors.

PMID- 9618426
TI  - Involvement of the central tachykinin NK1 receptor during maintenance of
      mechanical hypersensitivity induced by diabetes in the rat.
AB  - Our study examines the role of central and peripheral neurokinin1 (NK1) receptors
      in diabetes-induced mechanical hypersensitivity. Glycine, N, N-dimethyl-, 2-[[2
      [[(2-benzofuranylmethoxy)carbonyl]amino]-3-(1H-indol-3-yl)-2 -me thyl-1
      oxopropyl] amino]-2-phenylethylester, bisulfate, [R-(R*,R*)] (PD 156982) is a
      selective NK1 receptor antagonist with nanomolar affinity for the human (IC50 =
      1.4 nM) and guinea pig (IC50 = 9.6 nM) NK1 receptors. However, it has
      approximately two orders of magnitude lower affinity for the rodent NK1 receptor
      (IC50 = 820 nM). In electrophysiological studies, PD 156982 inhibited NK1
      receptor-mediated responses in the guinea pig locus ceruleus, in a competitive
      manner, with an equilibrium constant of 13.9 nM. The intracerebroventricular (10
      100 microg/animal) but not systemic administration of PD 156982 (1-100 mg/kg,
      s.c.) blocked the [Sar9, Met(O2)11] substance P-induced gerbil foot tapping
      response. This indicates that PD 156982 is unable to penetrate into the central
      nervous system. However, PD 156982 (10-100 mg/kg, s.c.) blocked the mechanical
      hypersensitivity induced by administration of substance P into the plantar
      surface of a rat paw. This suggests that PD 156982 can effectively antagonize
      peripheral NK1 receptors in vivo. The chemically related compound carbamic acid,
      [1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-2-[(1-phenylethyl)amino]et hyl ]-, 2
      benzofuranylmethyl ester, [R-(R*,S*)] (CI-1021) is also a selective NK1 receptor
      antagonist but can penetrate into the central nervous system. PD 156982 (10-100
      mg/kg, s.c.) failed to block streptozocin (75 mg/kg, i.p.) induced mechanical
      hypersensitivity. In contrast, CI-1021 dose-dependently (3-100 mg/kg, s.c.)
      blocked this hypersensitivity state with a minimum effective dose of 10 mg/kg. At
      these doses CI-1021 also antagonized mechanical hypersensitivity mediated by
      central NK1 but not NK2 receptors in the rat. It is suggested that the central
      NK1 receptor may play an important role in diabetes-induced hypersensitivity.

PMID- 9618427
TI  - Effect of antithyroid drugs on hydroxyl radical formation and alpha-1-proteinase
      inhibitor inactivation by neutrophils: therapeutic implications.
AB  - The release of proteolytic enzymes and generation of strong oxidants such as the
      hydroxyl radical by activated neutrophils has been proposed to play an important
      role in mediating toxin-induced liver injury. The antithyroid drug
      propylthiouracil protects against liver injury induced by many hepatotoxic agents
      and markedly reduces mortality in patients with alcoholic liver disease. However,
      the mechanism(s) by which propylthiouracil protects against liver injury is not
      well understood. The present studies investigate the effect of antithyroid drugs
      on proteolytic enzyme activity and on hydroxyl radical generation from activated
      neutrophils. In the presence of hydrogen peroxide and chloride, neutrophil
      myeloperoxidase, an enzyme from the same gene superfamily as thyroid peroxidase,
      generates hypochlorous acid which inactivates alpha-1-proteinase inhibitor (A1PI)
      present in serum. This inactivation allows neutrophil-released proteolytic
      enzymes to attack cells. In the present study myeloperoxidase activity was
      inhibited fully at therapeutic concentrations by antithyroid drugs
      (propylthiouracil and methimazole). Antithyroid drugs fully prevented
      hypochlorous acid formation, and prevented neutrophil-mediated inactivation of
      A1PI, with concomitant blockage of proteolytic activity. Conversely, generation
      of both superoxide and hydroxyl radicals by activated neutrophils was unaffected
      by propylthiouracil. The production of these oxygen radicals was fully inhibited
      by the NADPH oxidase inhibitor diphenylene iodonium chloride, however. These
      studies indicate that antithyroid drugs are unlikely to prevent cell injury by
      inhibiting hydroxyl radical generation or by scavenging hydroxyl radicals, but
      are likely to exert their hepatoprotective anti-inflammatory action by inhibiting
      neutrophil myeloperoxidase, an enzyme akin to thyroid peroxidase.

PMID- 9618428
TI  - GR196429: a nonindolic agonist at high-affinity melatonin receptors.
AB  - N-[2-[2,3,7,8-tetrahydro-1H-furo(2,3-g)indol-1-yl]ethyl]acetamide (GR196429) is a
      novel, nonindolic melatonin receptor agonist. GR196429 had high affinity for
      human mt1 (pKi 9.9) and MT2 (pKi 9.8) receptors expressed in Chinese hamster
      ovary cells and for 2-[125I]-iodomelatonin binding sites in human cerebellum,
      guinea pig superior colliculus and hypothalamus and chicken retina and tectum
      (pKi 8.8-9.5). GR196429 was inactive at a wide range of other hormone and
      neurotransmitter receptors. In Chinese hamster ovary cells expressing human mt1
      or MT2 receptors, both melatonin and GR196429 dose-dependently inhibited
      forskolin-stimulated cAMP accumulation. In rabbit isolated retina, GR196429
      inhibited calcium-dependent [3H]-dopamine release with potency (IC50 30 pM) and
      maximum effect (76 +/- 5% at 1 nM) similar to those of melatonin. The response
      was antagonized by the melatonin receptor antagonist luzindole (1 microM). In
      slices of rat brain suprachiasmatic nucleus, perfusion (1 h) with GR196429 at
      zeitgeber time 10 phase advanced the circadian peak in neuronal activity measured
      on the following day, with a maximum phase advance of 2.7 +/- 0.3 h at 10 pM and
      an EC50 of 0.6 pM, results that indicated a melatonin-like action on the phase of
      the circadian clock. CNS penetration and duration of receptor occupancy was
      determined in an ex vivo radioligand binding assay. In membranes of guinea pig
      superior colliculus prepared 30 min after administration of GR196429 (s.c.), 2
      [125I]-iodomelatonin binding was inhibited with an ED50 of 0.04 mg/kg. After a
      dose of 1 mg/kg, binding was significantly inhibited for at least 3 h. Thus
      GR196429 is a potent and selective agonist at high-affinity melatonin receptors,
      which modulates circadian rhythms in an in vitro model of the circadian clock and
      which readily penetrates the CNS.

PMID- 9618429
TI  - Long-acting blockade of biogenic amine transporters in rat brain by
      administration of the potent novel tropane 2beta-propanoyl-3beta-(2-Naphthyl)
      tropane.
AB  - 2beta-Propanoyl-3beta-(2-naphthyl)-tropane (WF-23) is a potent cocaine analog
      with activity at dopamine and serotonin transporters. The purpose of these
      experiments was to characterize the time course of effects of acute
      administration of WF-23 on spontaneous locomotion and biogenic amine
      transporters. Rats received injections i.p. with WF-23 (1 mg/kg), cocaine (30
      mg/kg) or vehicle and locomotor activity was measured at various times
      postinjection. Animals were killed immediately after behavioral activity.
      Locomotor activity was significantly increased by WF-23 administration, reaching
      maximum at 4 hr and persisting for 24 hr. Cocaine-elicited elevations in
      locomotor activity occurred only at the earliest times. WF-23 decreased DA
      transporter binding in striatal membranes ([125I]RTI-55 binding), with >50% loss
      in binding for up to 49 hr postinjection. WF-23 increased the Kd of the high
      affinity site, with no effect on Bmax. Cocaine depressed binding (20%) only at
      the earliest times. WF-23 decreased levels of [3H]WIN 35,428 binding sites up to
      95% of control in both dorsal and ventral striatum with a similar time-course
      when assessed autoradiographically. WF-23 also reduced [3H]citalopram binding to
      serotonin transporter sites throughout the brain. The slow onset and very long
      duration of action of WF-23, taken together with its actions at dopamine and
      serotonin transporters, suggest a potential role for treatment of disorders
      characterized by their involvement of these neural systems.

PMID- 9618430
TI  - Biosynthesis of sulfidopeptide leukotrienes via the transfer of leukotriene A4
      from polymorphonuclear cells to bovine retinal pericytes.
AB  - Administration of exogenous sulfidopeptide leukotrienes (LTs) is associated with
      enhanced microvascular permeability. In addition, endogenous LTs have been
      implicated as participants in permeability (nonhydrostatic) edema formation. The
      source of LTs for interaction with the microvasculature is, however, unknown. We
      hypothesized that pericytes contribute to vascular LT synthesis. Under basal
      conditions and after incubation with either the calcium ionophore, A23187 (0-1
      microM), or arachidonic acid (20 microM), bovine retinal pericytes (BRPs) did not
      produce significant amounts of sulfidopeptide LTs. In contrast, in the presence
      of polymorphonuclear leukocytes (PMNs), which can synthesize LTA4, but not
      sulfidopeptide leukotrienes, incubation of BRPs with A23187 resulted in dose
      dependent increases in LTC4/D4/E4 production (peak: 35.4 +/- 5 pg/microg protein;
      n = 12). Similarly, BRPs, incubated with exogenous, authentic LTA4 (10 microM),
      synthesized sulfidopeptide LTs (peak: 18.9 +/- 5 pg/microg protein, n = 3).
      Preincubation (30 min) of BRPs with PMNs and the lipoxygenase inhibitor,
      esculetin (1 x 10(-)4 M; n = 12), reduced peak A23187-induced production of LTs
      by 63.9 +/- 7%. Finally, Northern blot analysis revealed mRNA for 5-lipoxygenase
      to be present in human and bovine PMNs, but not in BRPs. These results suggest
      that pericytes produce sulfidopeptide LTs only when provided with LTA4 from an
      external source such as the PMN. Interactions between pericytes and PMNs may lead
      to the production of sulfidopeptide LTs, which, in turn, could alter
      microvascular permeability.

PMID- 9618431
TI  - Characterization of efflux transport of organic anions in a mouse brain capillary
      endothelial cell line.
AB  - Cumulative evidence suggests that several organic anions are actively effluxed
      from the brain to the blood across the blood-brain barrier (BBB). We examined the
      possibility of the presence of primary active transporters for organic anions
      (multidrug resistance associated protein (MRP) and canalicular multispecific
      organic anion transporter (cMOAT)) on the BBB by measuring the ATP-dependent
      uptake of 2,4-dinitrophenyl-S-glutathione (DNP-SG) and leukotriene C4 (LTC4) into
      membrane vesicles prepared from a cell line derived from mouse brain capillary
      endothelial cells (MBEC4). The ATP-dependent uptake of DNP-SG into the membrane
      vesicles was osmotically sensitive and was also supported by GTP, but not by AMP
      or ADP. An ATPase inhibitor, vanadate, blocked the ATP-dependent uptake of DNP
      SG. The ATP-dependent uptake process was saturable, with Km values of 0.56 and
      0.22 microM, and Vmax values of 5.5 and 27.5 pmol/min/mg protein for DNP-SG and
      LTC4, respectively. Northern and Western blot analyses showed the expression of
      murine MRP but not cMOAT in MBEC4 cells. Western blot analysis of the rat
      cerebral endothelial cells indicated the expression of protein(s) that is
      detectable with MRPr1, an antibody against MRP. These results, together with
      previous findings that both DNP-SG and LTC4 are good ligands for MRP, suggest
      that MRP is responsible for the unidirectional, energy-dependent efflux of
      organic anions from the brain into the circulating blood across the BBB.

PMID- 9618432
TI  - Protein kinase A maintains cellular tolerance to mu opioid receptor agonists in
      hypothalamic neurosecretory cells with chronic morphine treatment: convergence on
      a common pathway with estrogen in modulating mu opioid receptor/effector
      coupling.
AB  - The present study examined protein kinase A (PKA) and protein kinase C (PKC)
      involvement in the maintenance of cellular tolerance to mu opioid receptor
      agonists resulting from chronic opiate exposure in neurosecretory cells of the
      hypothalamic arcuate nucleus (ARC). The possibility that the diminution of mu
      opioid receptor/effector coupling produced by acute 17beta-estradiol or chronic
      opiate exposures is mediated by a common kinase pathway also was investigated.
      Intracellular recordings were made in hypothalamic slices prepared from
      ovariectomized female guinea pigs. The mu opioid receptor agonist D-Ala2, N-Me
      Phe4, Gly-ol5-enkephalin (DAMGO) produced dose-dependent hyperpolarizations of
      ARC neurons. Chronic morphine treatment for 4 days reduced DAMGO potency 2.5-fold
      with no change in the maximal response. This effect was mimicked by a 20-min bath
      application of the PKA activator cAMP, Sp-isomer, or the PKC activator phorbol
      12,13-dibutyrate. A 30-min bath application of the broad-spectrum protein kinase
      inhibitor staurosporine completely abolished the reduced DAMGO potency seen in
      morphine-tolerant neurosecretory cells, including those immunopositive for
      gonadotropin-releasing hormone. The effect of staurosporine was mimicked by the
      PKA inhibitor cAMP, Rp-isomer, but not by the PKC inhibitor calphostin C.
      Finally, a 20-min bath application of 17beta-estradiol did not further reduce
      DAMGO potency in morphine-tolerant ARC neurons. Therefore, increased PKA activity
      maintains cellular tolerance to mu opioid receptor agonists in ARC neurosecretory
      cells caused by chronic morphine treatment. Furthermore, acute 17beta-estradiol
      and chronic opiate treatments attenuate mu opioid receptor-mediated responses via
      a common PKA pathway.

PMID- 9618433
TI  - Preconditioning of rat heart with monophosphoryl lipid A: a role for nitric
      oxide.
AB  - Preconditioning with monophosphoryl lipid A (MLA) protects rabbit hearts from
      prolonged ischemic reperfusion injury by a mechanism involving inducible nitric
      oxide synthase (iNOS) activation. This study was undertaken to determine whether
      MLA also could precondition rat hearts in a similar manner. Rats were injected
      with two different doses of MLA (300 microg/kg or 450 microg/kg i.v.) or vehicle
      (control), and after 24 hr the animals were sacrificed for preparation of
      isolated perfused rat hearts. Hearts were then perfused by working mode, and then
      made ischemic for 30 min followed by 30 min of reperfusion. Another group of
      hearts were treated simultaneously with a nitric oxide (NO) blocker, L-nitro
      arginine-methyl-ester (L-NAME) (10 mg/kg) and MLA (450 microg/kg). For arrhythmia
      studies, 12 hearts were used in each group (total, 48 hearts). Cardiac functions
      were examined in a separate group of 24 hearts (n = 6/group). MLA-treated hearts
      (either dose) were tolerant to ischemic reperfusion injury as evidenced by
      improved postischemic ventricular recovery [coronary flow (ml/min) 19.1 +/- 0.8
      (300 microg/kg MLA), 22.6 +/- 1.0 (450 microg/kg MLA) vs. 15.9 +/- 0.7 (control);
      aortic flow (ml/min) 20.7 +/- 1.8 (300 microg/kg MLA), 25.8 +/- 1.4 (450
      microg/kg MLA) vs. 11. 0 +/- 0.8 (control); left ventricular developed pressure
      (kPa) 13.3 +/- 0.6 (300 microg/kg MLA), 14.6 +/- 0.2 (450 microg/kg MLA) vs. 10.
      3 +/- 0.7 (control)]. Incidences of ventricular fibrillation and ventricular
      tachycardia were decreased compared with the control group only in the 450
      microg/kg dose of MLA-treated hearts (92% to 33%). Pretreatment of the hearts
      with L-NAME inhibited the preconditioning effect of MLA. To examine the induction
      of the iNOS expression, RNAs were extracted from the control and MLA-treated
      hearts (after 2, 4,6, 8, 12 and 24 hr of treatment) and Northern blot analyses
      were performed with a specific cDNA probe for iNOS. A single band of
      approximately 4.6 kb corresponding to iNOS mRNA was detected after 4 hr of MLA
      treatment, whereas the maximal iNOS expression was found between 6 and 8 hr of
      MLA treatment. The results of this study demonstrated that MLA induced the
      expression of iNOS and protected the myocardium from ischemic reperfusion injury
      which is blocked by an inhibitor of NO synthesis, which suggests a role of NO in
      MLA-mediated cardioprotection.

PMID- 9618434
TI  - TAS-301, an inhibitor of smooth muscle cell migration and proliferation, inhibits
      intimal thickening after balloon injury to rat carotid arteries.
AB  - The purpose of this study was to determine the efficacy and the possible
      mechanism of action of a recently synthesized drug, TAS-301 [3-bis (4
      methoxyphenyl)methylene-2-indolinone], on intimal formation in comparison with
      those of tranilast, the clinical efficacy of which was reported earlier. Rat
      carotid arteries were injured using a balloon catheter. Neointimal thickening,
      measured 14 days after injury, was reduced by the oral administration of TAS-301
      in a dose-dependent fashion (3-100 mg/kg), and the effect of TAS-301 at a dose of
      100 mg/kg was significantly greater than that of tranilast (300 mg/kg). Fewer
      cells were found on the intima of balloon-injured arteries of TAS-301-treated
      rats than on arteries of tranilast-treated rats. In an in vitro assay, TAS-301
      inhibited the migration of smooth muscle cells (SMCs) stimulated by platelet
      derived growth factor-BB, insulin-like growth factor-1 or heparin-binding
      epidermal growth factor-like growth factor. In addition, TAS-301 and tranilast
      reduced the proliferation of medial and intimal SMCs at 4 and 8 days,
      respectively, after the injury. In vitro, TAS-301 inhibited basic fibroblast
      growth factor-induced proliferation of SMCs dose dependently. These findings
      indicate that TAS-301 shows a higher inhibitory potency on intimal formation than
      tranilast due to inhibition of both migration of medial SMCs and proliferation of
      medial and intimal SMCs. Our results suggest that further evaluation of TAS-301
      as an inhibitor of postangioplasty intimal thickening is warranted.

PMID- 9618435
TI  - Purification and characterization of heterologously expressed mouse CYP2A5 and
      CYP2G1: role in metabolic activation of acetaminophen and 2,6
      dichlorobenzonitrile in mouse olfactory mucosal microsomes.
AB  - The metabolic activation of two known olfactory mucosal (OM) toxicants,
      acetaminophen (AP) and 2,6-dichlorobenzonitrile (DCBN), was examined with mouse
      liver and OM microsomes and purified, heterologously expressed mouse CYP2A5 and
      CYP2G1. In reconstituted systems, both isoforms were active in metabolizing DCBN
      and AP to metabolites that formed protein adducts. The formation of DCBN- or AP
      protein adducts and other AP metabolites, including 3-hydroxy-AP and, in the
      presence of glutathione, AP-glutathione conjugate, was also detected in OM
      microsomal reactions and to a much greater extent than in liver microsomes.
      Evidence was obtained that CYP2A5 and CYP2G1 play major roles in mouse OM
      microsomal metabolic activation of DCBN and AP. Immunoblot analysis indicated
      that CYP2A5 and CYP2G1 are abundant P450 isoforms in OM microsomes. OM microsomal
      AP and DCBN metabolic activation was inhibited by 5- and 8-methoxsalen, which
      inhibit both CYP2A5 and CYP2G1, and by an inhibitory anti-CYP2A5 antibody that
      also inhibits CYP2G1. In addition, the roles of CYP1A2 and CYP2E1 in the OM
      bioactivation of AP and DCBN were ruled out by comparing activities of acetone
      treated mice or Cyp1a2(-/-) mice with those of control mice. Thus, CYP2A5 and
      CYP2G1 may both contribute to the known OM-selective toxicity of AP and DCBN.
      Further analysis of the kinetics of AP and DCBN metabolism by the purified P450s
      suggested that CYP2A5 may play a greater role in OM microsomal metabolism of AP,
      whereas their relative roles in DCBN metabolism may be dose dependent, with
      CYP2G1 playing more important roles at low substrate concentrations.

PMID- 9618436
TI  - Both the immunosuppressant SR31747 and the antiestrogen tamoxifen bind to an
      emopamil-insensitive site of mammalian Delta8-Delta7 sterol isomerase.
AB  - SR31747 is a novel agent that elicits immunosuppressive and anti-inflammatory
      effects. This drug was shown to inhibit Delta8-Delta7 sterol isomerase in yeast.
      To test whether this enzyme could also be an SR31747 target in mammals, the
      binding, antiproliferative and sterol biosynthesis inhibitory properties of
      various drugs were studied in recombinant sterol isomerase-producing yeast cells.
      Our results clearly show that SR31747 is a high affinity ligand of recombinant
      mammalian sterol isomerase (Kd = 1 nM). Tridemorph, a sterol biosynthesis
      inhibitor that is widely used in agriculture as an antifungal agent, is also a
      powerful inhibitor of murine and human sterol isomerases (IC50 value in the
      nanomolar range). Some drugs, like cis-flupentixol, trifluoperazine, 7
      ketocholestanol and tamoxifen, inhibit SR31747 binding only with the mammalian
      enzymes, whereas other drugs, like haloperidol and fenpropimorph, are much more
      effective with the yeast enzyme than with the mammalian ones. Emopamil, a high
      affinity ligand of human sterol isomerase, is inefficient in inhibiting SR31747
      binding to its mammalian target, suggesting that the SR31747 and emopamil binding
      sites on mammalian sterol isomerase do not overlap. In contrast, SR31747 binding
      inhibition by tamoxifen is very efficient and competitive (IC50 value in the
      nanomolar range), indicating that mammalian sterol isomerase contains a so-called
      antiestrogen binding site. Tamoxifen is found to selectively inhibit sterol
      biosynthesis at the sterol isomerase step in the cells that are producing the
      mammalian enzyme in place of their own sterol isomerase. Finally, we also show
      that tridemorph, a sterol biosynthesis inhibitor widely used in agriculture as an
      antifungal agent, is not selective of yeast Delta8-Delta7 sterol isomerase but is
      also highly efficient against murine Delta8-Delta7 sterol isomerase or human
      Delta8-Delta7 sterol isomerase. This observation contrasts with our already
      published results showing that fenpropimorph, another sterol isomerase inhibitor
      used in agriculture, is only poorly efficient against the mammalian enzymes.

PMID- 9618437
TI  - Inhibition of voltage-dependent sodium channels by the anticonvulsant gamma
      aminobutyric acid type A receptor modulator, 3-benzyl-3-ethyl-2-piperidinone.
AB  - 3-Benzyl-3-ethyl-2-piperidinone (3-BEP) belongs to a family of compounds that
      includes alpha- substituted gamma-butyrolactones, gamma-thiobutyrolactones, 2
      pyrrolidinones and hexahydro-2H-azepin-2-ones. Many of these drugs exhibit potent
      in vivo anticonvulsant activity in mice. Previous electrophysiological studies
      demonstrated that they potentiate gamma-aminobutyric acid- (GABA) mediated
      chloride currents. This GABAA receptor modulation was thought to be the main
      mechanism of anticonvulsant activity. We report that 3-BEP also modulates sodium
      channels. It decreased sodium currents in cultured rat hippocampal neurons in a
      voltage- and concentration-dependent manner. The drug's apparent affinity
      increased as neurons were depolarized. At a holding potential of -60 mV, the
      apparent IC50 was 487 microM. This concentration is comparable to its EC50 for
      GABAA modulation (575 microM). Current blockade occurred over all activation
      voltages tested. The steady state inactivation curve was shifted by 600 microM 3
      BEP from V50 = -65.3 mV to -72.0 mV, and recovery from inactivation was slowed
      from tau = 4.9 to 12.8 msec. Sodium current inhibition was not observed for three
      related compounds, suggesting a degree of chemical specificity for this activity.
      We conclude that in addition to its known effects on GABAA receptors, 3-BEP
      modulates sodium channels. Therefore this compound may prevent seizures by both
      enhancing inhibition and diminishing neuronal excitability.

PMID- 9618438
TI  - Opioid regulation of pallidal enkephalin release: bimodal effects of locally
      administered mu and delta opioid agonists in freely moving rats.
AB  - The globus pallidus and ventral pallidum receive dense enkephalinergic
      innervation from the dorsal and ventral striatum, respectively. A previous study
      demonstrated peripheral morphine administration to increase pallidal enkephalin
      release. To determine whether such opioid stimulatory effects may be mediated
      directly in the pallidum, in vivo microdialysis was used to study the effects of
      local administration of several concentrations of the mu receptor agonists
      morphine and morphine-6-glucuronide (M6G) as well as the the delta receptor
      agonist SNC80 on pallidal enkephalin release in freely moving rats. Low
      concentrations of morphine or M6G (1-10 nM) enhanced the release of enkephalins,
      an effect that was reversed by coadministration of the mu receptor antagonist
      beta-funaltrexamine (beta-FNA). A similar stimulatory effect was observed with a
      low concentration of SNC80 (50 nM), an effect that was blocked by the delta
      antagonist naltrindole (NTD). High concentrations of morphine (100 nM to 100
      microM) had little or no effect, whereas M6G (10 microM) suppressed enkephalin
      release, an effect that was reversed by beta-FNA. Similarly, a high concentration
      (5 microM) of SNC80 suppressed enkephalin release. However, this effect was not
      blocked by NTD but was attenuated by beta-FNA, suggesting a mu receptor-mediated
      action. These results offer in vivo evidence of bimodal (i.e., stimulatory and
      inhibitory) effects of mu and delta opioid agonists on enkephalin release in the
      pallidum.

PMID- 9618439
TI  - Identification of low molecular weight GP IIb/IIIa antagonists that bind
      preferentially to activated platelets.
AB  - A critical function of fibrinogen in hemostasis and thrombosis is to mediate
      platelet aggregation by binding selectively to an activated form of glycoprotein
      (GP) IIb/IIIa. Although numerous peptide and nonpeptide fibrinogen receptor
      antagonists have been described, their binding selectivity for resting and
      activated platelets has not been explored. Therefore, dissociation constants of
      GP IIb/IIIa antagonists for two biochemically separated forms of purified GP
      IIb/IIIa and for resting and activated platelets were determined by competitive
      displacement of the dansyl fluorophore containing GP IIb/IIIa antagonist L
      736,622. Also, coating either form of the purified GP IIb/IIIa onto yttrium
      silicate scintillation proximity assay fluomicrospheres produced an activated
      form of the receptor, whose binding affinity for GP IIb/IIIa antagonists was
      measured conveniently by competition with the arginine-glycine-aspartic acid
      (RGD) containing heptapeptide [125I]L-692,884. In addition, direct binding
      measurements with radiolabeled GP IIb/IIIa antagonists also were performed on
      resting and activated platelets. We identified two classes of compounds. One
      class binds to both forms of GP IIb/IIIa, as well as resting and activated
      platelets, with similar Kd values (e.g., L-736,622 and Echistatin). The other
      class of compounds binds with much higher affinity to the activated form of GP
      IIb/IIIa (purified or on platelets) as compared with the resting form (e.g., L
      734,217, MK-852, tirofiban and L-692,884). Selective antagonists, like L-734,217
      (KdActivated = 5 nM and KdResting = 620 nM), can effectively inhibit ex vivo
      platelet aggregation at concentrations of drug that produce low levels of
      occupancy of the circulating platelet receptors. The potential clinical
      advantages of selective versus nonselective GP IIb/IIIa antagonists remain to be
      explored in clinical trials.

PMID- 9618440
TI  - Metabolism of arachidonic acid to 20-hydroxy-5,8,11, 14-eicosatetraenoic acid by
      P450 enzymes in human liver: involvement of CYP4F2 and CYP4A11.
AB  - 20-Hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE) is a principal arachidonic
      acid (AA) metabolite formed via P450-dependent oxidation in hepatic and renal
      microsomes. Although 20-HETE plays an important role in the regulation of cell
      and/or organ physiology, the P450 enzyme(s) catalyzing its formation in humans
      remain undefined. In this study, we have characterized AA omega-hydroxylation to
      20-HETE by human hepatic microsomes and identified the underlying P450s. Analysis
      of microsomal AA omega-hydroxylation revealed biphasic kinetics (KM1 and VMAX1 =
      23 microM and 5.5 min-1; KM2 and VMAX2 = 144 microM and 18.8 min-1) consistent
      with catalysis by at least two enzymes. Of the human P450s examined, CYP4A11 and
      CYP4F2 were both potent AA omega-hydroxylases, exhibiting rates of 15.6 and 6.8
      nmol 20-HETE formed/min/nmol P450, respectively. Kinetic parameters of 20-HETE
      formation by CYP4F2 (KM = 24 microM; VMAX = 7.4 min-1) and CYP4A11 (KM = 228
      microM; VMAX = 49.1 min-1) resembled the low and high KM components,
      respectively, found in liver microsomes. Antibodies to CYP4F2 markedly inhibited
      (93.4 +/- 6%; n = 5) formation of 20-HETE by hepatic microsomes, whereas
      antibodies to CYP4A11 were much less inhibitory (13.0 +/- 9%; n = 5). Moreover, a
      strong correlation (r = 0.78; P < .02) was found between microsomal CYP4F2
      content and AA omega-hydroxylation among nine subjects. The correlation (r =
      0.76; P < .02) also noted between CYP4A11 content and 20-HETE formation stemmed
      from the relationship (r = 0.83; P < . 02) between hepatic CYP4A11 and CYP4F2
      levels in the subjects. Finally, immunoblot analysis revealed that in addition to
      liver, both P450s also were expressed in human kidney. Our results indicate that
      AA omega-hydroxylation in human liver is catalyzed by two enzymes of the CYP4
      gene family, namely CYP4F2 and CYP4A11, and that CYP4F2 underlies most 20-HETE
      formation occurring at relevant AA concentrations.

PMID- 9618441
TI  - Signalling in the yeasts: an informational cascade with links to the filamentous
      fungi.
AB  - All cells, from bacteria and yeasts to mammalian cells, respond to cues from
      their environment. A variety of mechanisms exist for the transduction of these
      external signals to the interior of the cell, resulting in altered patterns of
      protein activity. Eukaryotic cells commonly transduce external cues via a
      conserved module composed of three protein kinases, the mitogen-activated protein
      kinase (MAPK) cascade. This module can then activate substrates, some of which
      include transcriptional activators. Multiple MAPK signalling pathways coexist in
      a cell. This review considers different MAPK cascade signalling pathways that
      govern several aspects of the life cycle of budding and fission yeasts:
      conjugation and meiosis by the pheromone response pathway, stress response by the
      high-osmolarity sensing pathway, cell wall biosynthesis in response to activation
      of the low-osmolarity and heat-sensing pathway, and pseudohyphal growth in
      response to activation of a subset of the components of the pheromone response
      pathway. Because the MAPK cascade components are highly conserved, a key question
      in studies of these pathways is the mechanism by which specificity of response is
      achieved. Several other issues to be addressed in this review concern the nature
      of the receptors used to sense the external signals and the mechanism by which
      the receptors communicate with other components leading to activation of the MAPK
      cascade. Recently, it has become apparent that MAPK cascades are important in
      governing the pathogenicity of filamentous fungi.

PMID- 9618442
TI  - Short-sequence DNA repeats in prokaryotic genomes.
AB  - Short-sequence DNA repeat (SSR) loci can be identified in all eukaryotic and many
      prokaryotic genomes. These loci harbor short or long stretches of repeated
      nucleotide sequence motifs. DNA sequence motifs in a single locus can be
      identical and/or heterogeneous. SSRs are encountered in many different branches
      of the prokaryote kingdom. They are found in genes encoding products as diverse
      as microbial surface components recognizing adhesive matrix molecules and
      specific bacterial virulence factors such as lipopolysaccharide-modifying enzymes
      or adhesins. SSRs enable genetic and consequently phenotypic flexibility. SSRs
      function at various levels of gene expression regulation. Variations in the
      number of repeat units per locus or changes in the nature of the individual
      repeat sequences may result from recombination processes or polymerase inadequacy
      such as slipped-strand mispairing (SSM), either alone or in combination with DNA
      repair deficiencies. These rather complex phenomena can occur with relative ease,
      with SSM approaching a frequency of 10(-4) per bacterial cell division and
      allowing high-frequency genetic switching. Bacteria use this random strategy to
      adapt their genetic repertoire in response to selective environmental pressure.
      SSR-mediated variation has important implications for bacterial pathogenesis and
      evolutionary fitness. Molecular analysis of changes in SSRs allows
      epidemiological studies on the spread of pathogenic bacteria. The occurrence,
      evolution and function of SSRs, and the molecular methods used to analyze them
      are discussed in the context of responsiveness to environmental factors,
      bacterial pathogenicity, epidemiology, and the availability of full-genome
      sequences for increasing numbers of microorganisms, especially those that are
      medically relevant.

PMID- 9618443
TI  - Nontypeable Haemophilus influenzae: pathogenesis and prevention.
AB  - In this paper, we describe the ability of nontypeable Haemophilus influenzae
      (NTHi) to coexist with the human host and the devastating results associated with
      disruption of the delicate state of balanced pathogenesis, resulting in both
      acute and chronic respiratory tract infections. It has been seen that the strains
      of NTHi causing disease show a marked genetic and phenotypic diversity but that
      changes in the lipooligosaccharide (LOS) and protein size and antigenicity in
      chronically infected individuals indicate that individual strains of NTHi can
      remain and adapt themselves to avoid expulsion from their infective niche. The
      lack of reliance of NTHi on a single mechanism of attachment and its ability to
      interact with the host with rapid responses to its environment confirmed the
      success of this organism as both a colonizer and a pathogen. In vitro experiments
      on cell and organ cultures, combined with otitis media and pulmonary models in
      chinchillas, rats, and mice, have allowed investigations into individual
      interactions between NTHi and the mammalian host. The host-organism interaction
      appears to be a two-way process, with NTHi using cell surface structures to
      directly interact with the mammalian host and using secreted proteins and LOS to
      change the mammalian host in order to pave the way for colonization and invasion.
      Many experiments have also noted that immune system evasion through antigenic
      variation, secretion of enzymes and epithelial cell invasion allowed NTHi to
      survive for longer periods despite a specific immune response being mounted to
      infection. Several outer membrane proteins and LOS derivatives are discussed in
      relation to their efficacy in preventing pulmonary infections and otitis media in
      animals. General host responses with respect to age, genetic makeup, and vaccine
      delivery routes are considered, and a mucosal vaccine strategy is suggested.

PMID- 9618444
TI  - Acylation of Escherichia coli hemolysin: a unique protein lipidation mechanism
      underlying toxin function.
AB  - The pore-forming hemolysin (HlyA) of Escherichia coli represents a unique class
      of bacterial toxins that require a posttranslational modification for activity.
      The inactive protoxin pro-HlyA is activated intracellularly by amide linkage of
      fatty acids to two internal lysine residues 126 amino acids apart, directed by
      the cosynthesized HlyC protein with acyl carrier protein as the fatty acid donor.
      This action distinguishes HlyC from all bacterial acyltransferases such as the
      lipid A, lux-specific, and nodulation acyltransferases, and from eukaryotic
      transferases such as N-myristoyl transferases, prenyltransferases, and thioester
      palmitoyltransferases. Most lipids directly attached to proteins may be classed
      as N-terminal amide-linked and internal ester-linked acyl groups and C-terminal
      ether-linked isoprenoid groups. The acylation of HlyA and related toxins does not
      equate to these but does appear related to a small number of eukaryotic proteins
      that include inflammatory cytokines and mitogenic and cholinergic receptors.
      While the location and structure of lipid moieties on proteins vary, there are
      common effects on membrane affinity and/or protein-protein interactions. Despite
      being acylated at two residues, HlyA does not possess a "double-anchor" motif and
      does not have an electrostatic switch, although its dependence on calcium binding
      for activity suggests that the calcium-myristoyl switch may have relevance. The
      acyl chains on HlyA may provide anchorage points onto the surface of the host
      cell lipid bilayer. These could then enhance protein-protein interactions either
      between HlyA and components of a host signal transduction pathway to influence
      cytokine production or between HlyA monomers to bring about oligomerization
      during pore formation.

PMID- 9618446
TI  - Regulation of X-chromosome inactivation in development in mice and humans.
AB  - Dosage compensation for X-linked genes in mammals is accomplished by inactivating
      one of the two X chromosomes in females. X-chromosome inactivation (XCI) occurs
      during development, coupled with cell differentiation. In somatic cells, XCI is
      random, whereas in extraembryonic tissues, XCI is imprinted in that the
      paternally inherited X chromosome is preferentially inactivated. Inactivation is
      initiated from an X-linked locus, the X-inactivation center (Xic), and inactivity
      spreads along the chromosome toward both ends. XCI is established by complex
      mechanisms, including DNA methylation, heterochromatinization, and late
      replication. Once established, inactivity is stably maintained in subsequent cell
      generations. The function of an X-linked regulatory gene, Xist, is critically
      involved in XCI. The Xist gene maps to the Xic, it is transcribed only from the
      inactive X chromosome, and the Xist RNA associates with the inactive X chromosome
      in the nucleus. Investigations with Xist-containing transgenes and with deletions
      of the Xist gene have shown that the Xist gene is required in cis for XCI.
      Regulation of XCI is therefore accomplished through regulation of Xist.
      Transcription of the Xist gene is itself regulated by DNA methylation. Hence, the
      differential methylation of the Xist gene observed in sperm and eggs and its
      recognition by protein binding constitute the most likely mechanism regulating
      imprinted preferential expression of the paternal allele in preimplantation
      embryos and imprinted paternal XCI in extraembryonic tissues. This article
      reviews the mechanisms underlying XCI and recent advances elucidating the
      functions of the Xist gene in mice and humans.

PMID- 9618445
TI  - Yeast carbon catabolite repression.
AB  - Glucose and related sugars repress the transcription of genes encoding enzymes
      required for the utilization of alternative carbon sources; some of these genes
      are also repressed by other sugars such as galactose, and the process is known as
      catabolite repression. The different sugars produce signals which modify the
      conformation of certain proteins that, in turn, directly or through a regulatory
      cascade affect the expression of the genes subject to catabolite repression.
      These genes are not all controlled by a single set of regulatory proteins, but
      there are different circuits of repression for different groups of genes.
      However, the protein kinase Snf1/Cat1 is shared by the various circuits and is
      therefore a central element in the regulatory process. Snf1 is not operative in
      the presence of glucose, and preliminary evidence suggests that Snf1 is in a
      dephosphorylated state under these conditions. However, the enzymes that
      phosphorylate and dephosphorylate Snf1 have not been identified, and it is not
      known how the presence of glucose may affect their activity. What has been
      established is that Snf1 remains active in mutants lacking either the proteins
      Grr1/Cat80 or Hxk2 or the Glc7 complex, which functions as a protein phosphatase.
      One of the main roles of Snf1 is to relieve repression by the Mig1 complex, but
      it is also required for the operation of transcription factors such as Adr1 and
      possibly other factors that are still unidentified. Although our knowledge of
      catabolite repression is still very incomplete, it is possible in certain cases
      to propose a partial model of the way in which the different elements involved in
      catabolite repression may be integrated.

PMID- 9618451
TI  - Cell-to-cell communication in Escherichia coli and Salmonella typhimurium: they
      may be talking, but who's listening?

PMID- 9618452
TI  - Control of hematopoietic differentiation: lack of specificity in signaling by
      cytokine receptors.

PMID- 9618450
TI  - Biology of moderately halophilic aerobic bacteria.
AB  - The moderately halophilic heterotrophic aerobic bacteria form a diverse group of
      microorganisms. The property of halophilism is widespread within the bacterial
      domain. Bacterial halophiles are abundant in environments such as salt lakes,
      saline soils, and salted food products. Most species keep their intracellular
      ionic concentrations at low levels while synthesizing or accumulating organic
      solutes to provide osmotic equilibrium of the cytoplasm with the surrounding
      medium. Complex mechanisms of adjustment of the intracellular environments and
      the properties of the cytoplasmic membrane enable rapid adaptation to changes in
      the salt concentration of the environment. Approaches to the study of genetic
      processes have recently been developed for several moderate halophiles, opening
      the way toward an understanding of haloadaptation at the molecular level. The new
      information obtained is also expected to contribute to the development of novel
      biotechnological uses for these organisms.

PMID- 9618448
TI  - Replication and control of circular bacterial plasmids.
AB  - An essential feature of bacterial plasmids is their ability to replicate as
      autonomous genetic elements in a controlled way within the host. Therefore, they
      can be used to explore the mechanisms involved in DNA replication and to analyze
      the different strategies that couple DNA replication to other critical events in
      the cell cycle. In this review, we focus on replication and its control in
      circular plasmids. Plasmid replication can be conveniently divided into three
      stages: initiation, elongation, and termination. The inability of DNA polymerases
      to initiate de novo replication makes necessary the independent generation of a
      primer. This is solved, in circular plasmids, by two main strategies: (i) opening
      of the strands followed by RNA priming (theta and strand displacement
      replication) or (ii) cleavage of one of the DNA strands to generate a 3'-OH end
      (rolling-circle replication). Initiation is catalyzed most frequently by one or a
      few plasmid-encoded initiation proteins that recognize plasmid-specific DNA
      sequences and determine the point from which replication starts (the origin of
      replication). In some cases, these proteins also participate directly in the
      generation of the primer. These initiators can also play the role of pilot
      proteins that guide the assembly of the host replisome at the plasmid origin.
      Elongation of plasmid replication is carried out basically by DNA polymerase III
      holoenzyme (and, in some cases, by DNA polymerase I at an early stage), with the
      participation of other host proteins that form the replisome. Termination of
      replication has specific requirements and implications for reinitiation, studies
      of which have started. The initiation stage plays an additional role: it is the
      stage at which mechanisms controlling replication operate. The objective of this
      control is to maintain a fixed concentration of plasmid molecules in a growing
      bacterial population (duplication of the plasmid pool paced with duplication of
      the bacterial population). The molecules involved directly in this control can be
      (i) RNA (antisense RNA), (ii) DNA sequences (iterons), or (iii) antisense RNA and
      proteins acting in concert. The control elements maintain an average frequency of
      one plasmid replication per plasmid copy per cell cycle and can "sense" and
      correct deviations from this average. Most of the current knowledge on plasmid
      replication and its control is based on the results of analyses performed with
      pure cultures under steady-state growth conditions. This knowledge sets important
      parameters needed to understand the maintenance of these genetic elements in
      mixed populations and under environmental conditions.

PMID- 9618447
TI  - Type III protein secretion systems in bacterial pathogens of animals and plants.
AB  - Various gram-negative animal and plant pathogens use a novel, sec-independent
      protein secretion system as a basic virulence mechanism. It is becoming
      increasingly clear that these so-called type III secretion systems inject
      (translocate) proteins into the cytosol of eukaryotic cells, where the
      translocated proteins facilitate bacterial pathogenesis by specifically
      interfering with host cell signal transduction and other cellular processes.
      Accordingly, some type III secretion systems are activated by bacterial contact
      with host cell surfaces. Individual type III secretion systems direct the
      secretion and translocation of a variety of unrelated proteins, which account for
      species-specific pathogenesis phenotypes. In contrast to the secreted virulence
      factors, most of the 15 to 20 membrane-associated proteins which constitute the
      type III secretion apparatus are conserved among different pathogens. Most of the
      inner membrane components of the type III secretion apparatus show additional
      homologies to flagellar biosynthetic proteins, while a conserved outer membrane
      factor is similar to secretins from type II and other secretion pathways.
      Structurally conserved chaperones which specifically bind to individual secreted
      proteins play an important role in type III protein secretion, apparently by
      preventing premature interactions of the secreted factors with other proteins.
      The genes encoding type III secretion systems are clustered, and various pieces
      of evidence suggest that these systems have been acquired by horizontal genetic
      transfer during evolution. Expression of type III secretion systems is
      coordinately regulated in response to host environmental stimuli by networks of
      transcription factors. This review comprises a comparison of the structure,
      function, regulation, and impact on host cells of the type III secretion systems
      in the animal pathogens Yersinia spp., Pseudomonas aeruginosa, Shigella flexneri,
      Salmonella typhimurium, enteropathogenic Escherichia coli, and Chlamydia spp. and
      the plant pathogens Pseudomonas syringae, Erwinia spp., Ralstonia solanacearum,
      Xanthomonas campestris, and Rhizobium spp.

PMID- 9618453
TI  - V(D)J hypermutation and DNA mismatch repair: vexed by fixation.

PMID- 9618454
TI  - Prokaryotes: the unseen majority.
AB  - The number of prokaryotes and the total amount of their cellular carbon on earth
      are estimated to be 4-6 x 10(30) cells and 350-550 Pg of C (1 Pg = 10(15) g),
      respectively. Thus, the total amount of prokaryotic carbon is 60-100% of the
      estimated total carbon in plants, and inclusion of prokaryotic carbon in global
      models will almost double estimates of the amount of carbon stored in living
      organisms. In addition, the earth's prokaryotes contain 85-130 Pg of N and 9-14
      Pg of P, or about 10-fold more of these nutrients than do plants, and represent
      the largest pool of these nutrients in living organisms. Most of the earth's
      prokaryotes occur in the open ocean, in soil, and in oceanic and terrestrial
      subsurfaces, where the numbers of cells are 1.2 x 10(29), 2.6 x 10(29), 3.5 x
      10(30), and 0. 25-2.5 x 10(30), respectively. The numbers of heterotrophic
      prokaryotes in the upper 200 m of the open ocean, the ocean below 200 m, and soil
      are consistent with average turnover times of 6-25 days, 0.8 yr, and 2.5 yr,
      respectively. Although subject to a great deal of uncertainty, the estimate for
      the average turnover time of prokaryotes in the subsurface is on the order of 1-2
      x 10(3) yr. The cellular production rate for all prokaryotes on earth is
      estimated at 1.7 x 10(30) cells/yr and is highest in the open ocean. The large
      population size and rapid growth of prokaryotes provides an enormous capacity for
      genetic diversity.

PMID- 9618455
TI  - Ozonolysis for selectively depolymerizing polysaccharides containing beta-D
      aldosidic linkages.
AB  - The depolymerization of polysaccharides, particularly those containing acid
      sensitive components, into intact constituent repeating units can be very
      difficult. We describe a method using ozonolysis for depolymerizing
      polysaccharides containing beta-D-aldosidic linkages into short-chain
      polysaccharides and oligosaccharides. This method is carried out on
      polysaccharides that have been fully acetylated whereby beta-D-aldosidic linkages
      are selectively oxidized by ozone to form esters, from which the polysaccharides
      are subsequently cleaved with a nucleophile. Ozone oxidation of aldosidic
      linkages proceeds under strong stereoelectronic control, and reaction rates
      depend on the conformations of glycosidic linkages. Thus, beta-D-aldosidic
      linkages with different conformations can have very different reaction rates even
      in the absence of substantial chemical differences. These rate differences
      allowed for very high selectivity in cleaving beta-D-linkages of polysaccharides.
      Several polysaccharides from group B Streptococcus and other bacterial species
      were selectively depolymerized with this method. The repeating units of the group
      B Streptococcus polysaccharides all contain an acid-sensitive sialic acid residue
      in a terminal position on a side chain and several beta-D-residues including
      galactose, glucose, and N-acetylglucosamine; however, with each polysaccharide,
      one type of linkage was more reactive than others. Selective cleavage of the most
      sensitive linkage occurs randomly throughout the polymer chain, yielding
      fragments of controllable and narrowly distributed sizes and the same repeating
      unit structure. The average size of the molecules decreases exponentially, and
      desired sizes can be obtained by stopping the reaction at appropriate time
      points. With this method the labile sialic acid residue was not affected.

PMID- 9618457
TI  - Orientation in operator algebras.
AB  - A concept of orientation is relevant for the passage from Jordan structure to
      associative structure in operator algebras. The research reported in this paper
      bridges the approach of Connes for von Neumann algebras and ourselves for C*
      algebras in a general theory of orientation that is of geometric nature and is
      related to dynamics.

PMID- 9618456
TI  - Microvascular and tissue oxygen gradients in the rat mesentery.
AB  - One of the most important functions of the blood circulation is O2 delivery to
      the tissue. This process occurs primarily in microvessels that also regulate
      blood flow and are the site of many metabolic processes that require O2. We
      measured the intraluminal and perivascular pO2 in rat mesenteric arterioles in
      vivo by using noninvasive phosphorescence quenching microscopy. From these
      measurements, we calculated the rate at which O2 diffuses out of microvessels
      from the blood. The rate of O2 efflux and the O2 gradients found in the immediate
      vicinity of arterioles indicate the presence of a large O2 sink at the interface
      between blood and tissue, a region that includes smooth muscle and endothelium.
      Mass balance analyses show that the loss of O2 from the arterioles in this
      vascular bed primarily is caused by O2 consumption in the microvascular wall. The
      high metabolic rate of the vessel wall relative to parenchymal tissue in the rat
      mesentery suggests that in addition to serving as a conduit for the delivery of
      O2 the microvasculature has other functions that require a significant amount of
      O2.

PMID- 9618449
TI  - Molecular genetics of the RNA polymerase II general transcriptional machinery.
AB  - Transcription initiation by RNA polymerase II (RNA pol II) requires interaction
      between cis-acting promoter elements and trans-acting factors. The eukaryotic
      promoter consists of core elements, which include the TATA box and other DNA
      sequences that define transcription start sites, and regulatory elements, which
      either enhance or repress transcription in a gene-specific manner. The core
      promoter is the site for assembly of the transcription preinitiation complex,
      which includes RNA pol II and the general transcription fctors TBP, TFIIB, TFIIE,
      TFIIF, and TFIIH. Regulatory elements bind gene-specific factors, which affect
      the rate of transcription by interacting, either directly or indirectly, with
      components of the general transcriptional machinery. A third class of
      transcription factors, termed coactivators, is not required for basal
      transcription in vitro but often mediates activation by a broad spectrum of
      activators. Accordingly, coactivators are neither gene-specific nor general
      transcription factors, although gene-specific coactivators have been described in
      metazoan systems. Transcriptional repressors include both gene-specific and
      general factors. Similar to coactivators, general transcriptional repressors
      affect the expression of a broad spectrum of genes yet do not repress all genes.
      General repressors either act through the core transcriptional machinery or are
      histone related and presumably affect chromatin function. This review focuses on
      the global effectors of RNA polymerase II transcription in yeast, including the
      general transcription factors, the coactivators, and the general repressors.
      Emphasis is placed on the role that yeast genetics has played in identifying
      these factors and their associated functions.

PMID- 9618458
TI  - Bacteria lacking a multidrug pump: a sensitive tool for drug discovery.
AB  - Microorganisms express multidrug resistance pumps (MDRs) that can confound
      antibiotic discovery. We propose the use of mutants deficient in MDRs to overcome
      this problem. Sensitivity to quinolones and to amphipathic cations (norfloxacin,
      benzalkonium chloride, cetrimide, pentamidine, etc.) was increased 5- to 30-fold
      in a Staphylococcus aureus mutant with a disrupted chromosomal copy of the NorA
      MDR. NorA was required both for increased sensitivity to drugs in the presence of
      an MDR inhibitor and for increased rate of cation efflux. This requirement
      suggests that NorA is the major MDR protecting S. aureus from the antimicrobials
      studied. A 15- to 60-fold increase in sensitivity to antimicrobials also was
      observed in wild-type cells at an alkaline pH that favors accumulation of cations
      and weak bases. This effect was synergistic with a norA mutation, resulting in an
      increase up to 1,000-fold in sensitivity to antimicrobials. The usefulness of
      applying MDR mutants for natural product screening was demonstrated further by
      increased sensitivity of the norA- strain to plant alkaloid antimicrobials, which
      might be natural MDR substrates.

PMID- 9618459
TI  - Interacting helical faces of subunits a and c in the F1Fo ATP synthase of
      Escherichia coli defined by disulfide cross-linking.
AB  - Subunits a and c of Fo are thought to cooperatively catalyze proton translocation
      during ATP synthesis by the Escherichia coli F1Fo ATP synthase. Optimizing
      mutations in subunit a at residues A217, I221, and L224 improves the partial
      function of the cA24D/cD61G double mutant and, on this basis, these three
      residues were proposed to lie on one face of a transmembrane helix of subunit a,
      which then interacted with the transmembrane helix of subunit c anchoring the
      essential aspartyl group. To test this model, in the present work Cys residues
      were introduced into the second transmembrane helix of subunit c and the
      predicted fourth transmembrane helix of subunit a. After treating the membrane
      vesicles of these mutants with Cu(1, 10-phenanthroline)2SO4 at 0 degrees, 10
      degrees, or 20 degreesC, strong a-c dimer formation was observed at all three
      temperatures in membranes of 7 of the 65 double mutants constructed, i.e., in the
      aS207C/cI55C, aN214C/cA62C, aN214C/cM65C, aI221C/cG69C, aI223C/cL72C,
      aL224C/cY73C, and aI225C/cY73C double mutant proteins. The pattern of cross
      linking aligns the helices in a parallel fashion over a span of 19 residues with
      the aN214C residue lying close to the cA62C and cM65C residues in the middle of
      the membrane. Lesser a-c dimer formation was observed in nine other double
      mutants after treatment at 20 degreesC in a pattern generally supporting that
      indicated by the seven landmark residues cited above. Cross-link formation was
      not observed between helix-1 of subunit c and helix-4 of subunit a in 19
      additional combinations of doubly Cys-substituted proteins. These results provide
      direct chemical evidence that helix-2 of subunit c and helix-4 of subunit a pack
      close enough to each other in the membrane to interact during function. The
      proximity of helices supports the possibility of an interaction between Arg210 in
      helix-4 of subunit a and Asp61 in helix-2 of subunit c during proton
      translocation, as has been suggested previously.

PMID- 9618460
TI  - Structure and function of the Bacillus hybrid enzyme GluXyn-1: native-like
      jellyroll fold preserved after insertion of autonomous globular domain.
AB  - The 1,3-1,4-beta-glucanase from Bacillus macerans (wtGLU) and the 1, 4-beta
      xylanase from Bacillus subtilis (wtXYN) are both single-domain jellyroll proteins
      catalyzing similar enzymatic reactions. In the fusion protein GluXyn-1, the two
      proteins are joined by insertion of the entire XYN domain into a surface loop of
      cpMAC-57, a circularly permuted variant of wtGLU. GluXyn-1 was generated by
      protein engineering methods, produced in Escherichia coli and shown to fold
      spontaneously and have both enzymatic activities at wild-type level. The crystal
      structure of GluXyn-1 was determined at 2.1 A resolution and refined to R = 17.7%
      and R(free) = 22.4%. It shows nearly ideal, native-like folding of both protein
      domains and a small, but significant hinge bending between the domains. The
      active sites are independent and accessible explaining the observed enzymatic
      activity. Because in GluXyn-1 the complete XYN domain is inserted into the
      compact folding unit of GLU, the wild-type-like activity and tertiary structure
      of the latter proves that the folding process of GLU does not depend on
      intramolecular interactions that are short-ranged in the sequence. Insertion
      fusions of the GluXyn-1 type may prove to be an easy route toward more stable
      bifunctional proteins in which the two parts are more closely associated than in
      linear end-to-end protein fusions.

PMID- 9618461
TI  - Lignin monomer composition is determined by the expression of a cytochrome P450
      dependent monooxygenase in Arabidopsis.
AB  - The phenylpropanoid pathway provides precursors for the biosynthesis of soluble
      secondary metabolites and lignin in plants. Ferulate-5-hydroxylase (F5H)
      catalyzes an irreversible hydroxylation step in this pathway that diverts ferulic
      acid away from guaiacyl lignin biosynthesis and toward sinapic acid and syringyl
      lignin. This fact led us to postulate that F5H was a potential regulatory step in
      the determination of lignin monomer composition. To test this hypothesis, we have
      used Arabidopsis to examine the impact of F5H overexpression. Arabidopsis is a
      useful model system in which to study lignification because in wild-type plants,
      guaiacyl and syringyl lignins are deposited in a tissue-specific fashion, while
      the F5H-deficient fah1 mutant accumulates only guaiacyl lignin. Here we show that
      ectopic overexpression of F5H in Arabidopsis abolishes tissue-specific lignin
      monomer accumulation. Surprisingly, overexpression of F5H under the control of
      the lignification-associated cinnamate-4-hydroxylase promoter, but not the
      commonly employed cauliflower mosaic virus 35S promoter, generates a lignin that
      is almost entirely comprised of syringylpropane units. These experiments
      demonstrate that modification of F5H expression may enable engineering of lignin
      monomer composition in agronomically important plant species.

PMID- 9618462
TI  - The design, computer modeling, solution structure, and biological evaluation of
      synthetic analogs of bryostatin 1.
AB  - The bryostatins are a unique family of emerging cancer chemotherapeutic
      candidates isolated from marine bryozoa. Although the biochemical basis for their
      therapeutic activity is not known, these macrolactones exhibit high affinities
      for protein kinase C (PKC) isozymes, compete for the phorbol ester binding site
      on PKC, and stimulate kinase activity in vitro and in vivo. Unlike the phorbol
      esters, they are not first-stage tumor promoters. The design, computer modeling,
      NMR solution structure, PKC binding, and functional assays of a unique class of
      synthetic bryostatin analogs are described. These analogs (7b, 7c, and 8) retain
      the putative recognition domain of the bryostatins but are simplified through
      deletions and modifications in the C4-C14 spacer domain. Computer modeling of an
      analog prototype (7a) indicates that it exists preferentially in two distinct
      conformational classes, one in close agreement with the crystal structure of
      bryostatin 1. The solution structure of synthetic analog 7c was determined by NMR
      spectroscopy and found to be very similar to the previously reported structures
      of bryostatins 1 and 10. Analogs 7b, 7c, and 8 bound strongly to PKC isozymes
      with Ki = 297, 3.4, and 8.3 nM, respectively. Control 7d, like the corresponding
      bryostatin derivative, exhibited weak PKC affinity, as did the derivative, 9,
      lacking the spacer domain. Like bryostatin, acetal 7c exhibited significant
      levels of in vitro growth inhibitory activity (1.8-170 ng/ml) against several
      human cancer cell lines, providing an important step toward the development of
      simplified, synthetically accessible analogs of the bryostatins.

PMID- 9618463
TI  - Structural basis for chemical inhibition of human blood coagulation factor Xa.
AB  - Factor Xa, the converting enzyme of prothrombin to thrombin, has emerged as an
      alternative (to thrombin) target for drug discovery for thromboembolic diseases.
      An inhibitor has been synthesized and the crystal structure of the complex
      between Des[1-44] factor Xa and the inhibitor has been determined by
      crystallographic methods in two different crystal forms to 2.3- and 2.4-A
      resolution. The racemic mixture of inhibitor FX-2212, (2RS)-(3'-amidino-3
      biphenylyl)-5-(4-pyridylamino)pentanoic acid, inhibits factor Xa activity by 50%
      at 272 nM in vitro. The S-isomer of FX-2212 (FX-2212a) was found to bind to the
      active site of factor Xa in both crystal forms. The biphenylamidine of FX-2212a
      occupies the S1-pocket, and the pyridine ring makes hydrophobic interactions with
      the factor Xa aryl-binding site. Several water molecules meditate inhibitor
      binding to residues in the active site. In contrast to the earlier crystal
      structures of factor Xa, such as those of apo-Des[1-45] factor Xa and Des[1-44]
      factor Xa in complex with a naphthyl inhibitor DX-9065a, two epidermal growth
      factor-like domains of factor Xa are well ordered in both our crystal forms as
      well as the region between the two domains, which recently was found to be the
      binding site of the effector cell protease receptor-1. This structure provides a
      basis for designing next generation inhibitors of factor Xa.

PMID- 9618464
TI  - Analysis of human cytochrome P450 3A4 cooperativity: construction and
      characterization of a site-directed mutant that displays hyperbolic steroid
      hydroxylation kinetics.
AB  - Cytochrome P450 3A4 is generally considered to be the most important human drug
      metabolizing enzyme and is known to catalyze the oxidation of a number of
      substrates in a cooperative manner. An allosteric mechanism is usually invoked to
      explain the cooperativity. Based on a structure-activity study from another
      laboratory using various effector-substrate combinations and on our own studies
      using site-directed mutagenesis and computer modeling of P450 3A4, the most
      likely location of effector binding is in the active site along with the
      substrate. Our study was designed to test this hypothesis by replacing residues
      Leu-211 and Asp-214 with the larger Phe and Glu, respectively. These residues
      were predicted to constitute a portion of the effector binding site, and the
      substitutions were designed to mimic the action of the effector by reducing the
      size of the active site. The L211F/D214E double mutant displayed an increased
      rate of testosterone and progesterone 6beta-hydroxylation at low substrate
      concentrations and a decreased level of heterotropic stimulation elicited by
      alpha-naphthoflavone. Kinetic analyses of the double mutant revealed the absence
      of homotropic cooperativity with either steroid substrate. At low substrate
      concentrations the steroid 6beta-hydroxylase activity of the wild-type enzyme was
      stimulated by a second steroid, whereas L211F/D214E displayed simple substrate
      inhibition. To analyze L211F/D214E at a more mechanistic level, spectral binding
      studies were carried out. Testosterone binding by the wild-type enzyme displayed
      homotropic cooperativity, whereas substrate binding by L211F/D214E displayed
      hyperbolic behavior.

PMID- 9618465
TI  - Cloning and characterization of human protease-activated receptor 4.
AB  - Protease-activated receptors 1-3 (PAR1, PAR2, and PAR3) are members of a unique G
      protein-coupled receptor family. They are characterized by a tethered peptide
      ligand at the extracellular amino terminus that is generated by minor
      proteolysis. A partial cDNA sequence of a fourth member of this family (PAR4) was
      identified in an expressed sequence tag database, and the full-length cDNA clone
      has been isolated from a lymphoma Daudi cell cDNA library. The ORF codes for a
      seven transmembrane domain protein of 385 amino acids with 33% amino acid
      sequence identity with PAR1, PAR2, and PAR3. A putative protease cleavage site
      (Arg-47/Gly-48) was identified within the extracellular amino terminus. COS cells
      transiently transfected with PAR4 resulted in the formation of intracellular
      inositol triphosphate when treated with either thrombin or trypsin. A PAR4 mutant
      in which the Arg-47 was replaced with Ala did not respond to thrombin or trypsin.
      A hexapeptide (GYPGQV) representing the newly exposed tethered ligand from the
      amino terminus of PAR4 after proteolysis by thrombin activated COS cells
      transfected with either wild-type or the mutant PAR4. Northern blot showed that
      PAR4 mRNA was expressed in a number of human tissues, with high levels being
      present in lung, pancreas, thyroid, testis, and small intestine. By fluorescence
      in situ hybridization, the human PAR4 gene was mapped to chromosome 19p12.

PMID- 9618466
TI  - Structural homologies with ATP- and folate-binding enzymes in the crystal
      structure of folylpolyglutamate synthetase.
AB  - Folylpolyglutamate synthetase, which is responsible for the addition of a
      polyglutamate tail to folate and folate derivatives, is an ATP-dependent enzyme
      isolated from eukaryotic and bacterial sources, where it plays a key role in the
      retention of the intracellular folate pool. Here, we report the 2.4-A resolution
      crystal structure of the MgATP complex of the enzyme from Lactobacillus casei.
      The structural analysis reveals that folylpolyglutamate synthetase is a modular
      protein consisting of two domains, one with a typical mononucleotide-binding fold
      and the other strikingly similar to the folate-binding enzyme dihydrofolate
      reductase. We have located the active site of the enzyme in a large interdomain
      cleft adjacent to an ATP-binding P-loop motif. Opposite this site, in the C
      domain, a cavity likely to be the folate binding site has been identified, and
      inspection of this cavity and the surrounding protein structure suggests that the
      glutamate tail of the substrate may project into the active site. A further
      feature of the structure is a well defined Omega loop, which contributes both to
      the active site and to interdomain interactions. The determination of the
      structure of this enzyme represents the first step toward the elucidation of the
      molecular mechanism of polyglutamylation of folates and antifolates.

PMID- 9618467
TI  - Functional transitions in myosin: formation of a critical salt-bridge and
      transmission of effect to the sensitive tryptophan.
AB  - For analyzing the mechanism of energy transduction in the "motor" protein,
      myosin, it is opportune both to model the structural change in the hydrolytic
      transition, ATP (myosin-bound) + H2O --> ADP.Pi (myosin-bound) and to check the
      plausibility of the model by appropriate site-directed mutations in the
      functional system. Here, we made a series of mutations to investigate the role of
      the salt-bridge between Glu-470 and Arg-247 (of chicken smooth muscle myosin)
      that has been inferred from crystallography to be a central feature of the
      transition [Fisher, A. J., Smith, C. A., Thoden, J. B. , Smith, R., Sutoh, K.,
      Holden, H. M., & Rayment, I. (1995) Biochemistry 34, 8960-8972]. Our results
      suggest that whether in the normal, or in the inverted, direction an intact salt
      bridge is necessary for ATP hydrolysis, but when the salt-bridge is in the
      inverted direction it does not support actin activation. Normally, fluorescence
      changes result from adding nucleotides to myosin; these signals are reported by
      Trp-512 (of chicken smooth muscle myosin). Our results also suggest that
      structural impairments in the 470-247 region interfere with the transmission of
      these signals to the responsive Trp.

PMID- 9618468
TI  - Isolation of a myoglobin molten globule by selective cobalt(III)-induced
      unfolding.
AB  - Reaction of the Schiff-base complex [Co(acetylacetonate-ethylenediimine)(NH3)2]+
      with metmyoglobin at pH 6.5 yields a partially folded protein containing six
      Co(III) complexes. Although half of its alpha-helical secondary structure is
      retained, absorption and CD spectra indicate that the tertiary structure in both
      B-F and AGH domains is disrupted in the partially folded protein. In analogy to
      proton-induced unfolding, it is likely that the loss of tertiary structure is
      triggered by metal-ion binding to histidines. Cobalt(III)-induced unfolding of
      myoglobin is unique in its selectivity (other proteins are unaffected) and in
      allowing the isolation of the partially folded macromolecule (the protein does
      not refold or aggregate upon removal of free denaturant).

PMID- 9618469
TI  - A cobalt complex that selectively disrupts the structure and function of zinc
      fingers.
AB  - Zinc finger domains are structures that mediate sequence recognition for a large
      number of DNA-binding proteins. These domains consist of sequences of amino acids
      containing cysteine and histidine residues tetrahedrally coordinated to a zinc
      ion. In this report, we present a means to selectively inhibit a zinc finger
      transcription factor with cobalt(III) Schiff-base complexes. 1H NMR spectroscopy
      confirmed that the structure of a zinc finger peptide is disrupted by axial
      ligation of the cobalt(III) complex to the nitrogen of the imidazole ring of a
      histidine residue. Fluorescence studies reveal that the zinc ion is displaced
      from the model zinc finger peptide in the presence of the cobalt complex. In
      addition, gel-shift and filter-binding assays reveal that cobalt complexes
      inhibit binding of a complete zinc finger protein, human transcription factor
      Sp1, to its consensus sequence. Finally, a DNA-coupled conjugate of the cobalt
      complexes selectively inhibited Sp1 in the presence of several other
      transcription factors.

PMID- 9618470
TI  - Assembly, subunit composition, and footprint of human DNA repair excision
      nuclease.
AB  - The assembly and composition of human excision nuclease were investigated by
      electrophoretic mobility shift assay and DNase I footprinting. Individual repair
      factors or any combination of up to four repair factors failed to form DNA
      protein complexes of high specificity and stability. A stable complex of high
      specificity can be detected only when XPA/RPA, transcription factor IIH,
      XPC.HHR23B, and XPG and ATP are present in the reaction mixture. The XPF.ERCC1
      heterodimer changes the electrophoretic mobility of the DNA-protein complex
      formed with the other five repair factors, but it does not confer additional
      specificity. By using proteins with peptide tags or antibodies to the repair
      factors in electrophoretic mobility shift assays, it was found that XPA,
      replication protein A, transcription factor IIH, XPG, and XPF.excision repair
      cross-complementing 1 but not XPC.HHR23B were present in the penultimate and
      ultimate dual incision complexes. Thus, it appears that XPC.HHR23B is a molecular
      matchmaker that participates in the assembly of the excision nuclease but is not
      present in the ultimate dual incision complex. The excision nuclease makes an
      assymmetric DNase I footprint of approximately 30 bp around the damage and
      increases the DNase I sensitivity of the DNA on both sides of the footprint.

PMID- 9618471
TI  - Reexamination of the mechanism of hydroxyl radical adducts formed from the
      reaction between familial amyotrophic lateral sclerosis-associated Cu,Zn
      superoxide dismutase mutants and H2O2.
AB  - Amyotrophic lateral sclerosis (ALS) involves the progressive degeneration of
      motor neurons in the spinal cord and motor cortex. Mutations to Cu,Zn superoxide
      dismutase (SOD) linked with familial ALS are reported to increase hydroxyl
      radical adduct formation from hydrogen peroxide as measured by spin trapping with
      5, 5'-dimethyl-1-pyrrolline N-oxide (DMPO). In the present study, we have used
      oxygen-17-enriched water and H2O2 to reinvestigate the mechanism of DMPO/.OH
      formation from the SOD and SOD mutants. The relative ratios of DMPO/.17OH and
      DMPO/.16OH formed in the Fenton reaction were 90% and 10%, respectively,
      reflecting the ratios of H217O2 to H216O2. The reaction of the WT SOD with H217O2
      in bicarbonate/CO2 buffer yielded 63% DMPO/.17OH and 37% DMPO/.16OH. Similar
      results were obtained from the reaction between familial ALS SOD mutants and
      H217O2: DMPO/.17OH (64%); DMPO/.16OH (36%) from A4V and DMPO/.17OH (62%); and
      DMPO/.16OH (38%) from G93A. These results were confirmed further by using 5
      diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide spin trap, a phosphorylated
      analog of DMPO. Contrary to earlier reports, the present results indicate that a
      significant fraction of DMPO/.OH formed during the reaction of SOD and familial
      ALS SOD mutants with H2O2 is derived from the incorporation of oxygen from water
      due to oxidation of DMPO to DMPO/.OH presumably via DMPO radical cation. No
      differences were detected between WT and mutant SODs, neither in the
      concentration of DMPO/.OH or DEPMPO/.OH formed nor in the relative incorporation
      of oxygen from H2O2 or water.

PMID- 9618472
TI  - Non-p53 p53RE binding protein, a human transcription factor functionally
      analogous to P53.
AB  - The transactivation activity of the p53 tumor suppressor protein is critical for
      regulating cell growth and apoptosis. We describe the identification of a
      transcription factor that is functionally similar to p53 and contains the same
      DNA binding and transcription activities specific for the p53 responsive DNA
      element (p53RE). This protein was highly purified through chromatography from
      HeLa cell extracts. The purified protein was able to bind specifically to the
      p53RE derived from a p21(waf1) promoter and to stimulate p53RE-dependent
      transcription but not basal transcription in vitro. Its DNA-binding activity was
      inhibited by the wild type but not mutant p53RE-containing DNA oligomers. Also,
      this p53RE-binding activity was found in human p53 null Saos-2 osteosarcoma and
      H1299 small cell lung carcinoma cells. Interestingly, this activity exhibited a
      p53RE sequence preference that was distinct from the p53 protein. The activity is
      neither p53 nor p73, because anti-p53 or anti-73 antibodies were unable to detect
      this purified protein nor were the antibodies able to alter the p53-like
      activity, the p53RE-protein complex. These results demonstrate that, besides p73,
      an additional p53-like protein exists in cells, which is named NBP for non-p53,
      p53RE binding protein.

PMID- 9618473
TI  - The RIIbeta regulatory subunit of protein kinase A binds to cAMP response
      element: an alternative cAMP signaling pathway.
AB  - cAMP, through the activation of cAMP-dependent protein kinase (PKA), is involved
      in transcriptional regulation. In eukaryotic cells, cAMP is not considered to
      alter the binding affinity of CREB/ATF to cAMP-responsive element (CRE) but to
      induce serine phosphorylation and consequent increase in transcriptional
      activity. In contrast, in prokaryotic cells, cAMP enhances the DNA binding of the
      catabolite repressor protein to regulate the transcription of several operons.
      The structural similarity of the cAMP binding sites in catabolite repressor
      protein and regulatory subunit of PKA type II (RII) suggested the possibility of
      a similar role for RII in eukaryotic gene regulation. Herein we report that
      RIIbeta subunit of PKA is a transcription factor capable of interacting
      physically and functionally with a CRE. In contrast to CREB/ATF, the binding of
      RIIbeta to a CRE was enhanced by cAMP, and in addition, RIIbeta exhibited
      transcriptional activity as a Gal4-RIIbeta fusion protein. These experiments
      identify RIIbeta as a component of an alternative pathway for regulation of CRE
      directed transcription in eukaryotic cells.

PMID- 9618474
TI  - Deposition-related sites K5/K12 in histone H4 are not required for nucleosome
      deposition in yeast.
AB  - Histone H4 can be acetylated at N-terminal lysines K5, K8, K12, and K16, but
      newly synthesized H4 is diacetylated at K5/K12 in diverse organisms. This pattern
      is widely thought to be important for histone deposition onto replicating DNA. To
      investigate the importance of K5/K12 we have mutagenized these lysines in yeast
      and assayed for nucleosome assembly. Assaying was done in the absence of the
      histone H3 N terminus, which has functions redundant with those of H4 in histone
      deposition. Nucleosome assembly was assayed by three methods. Because nucleosome
      depletion may be lethal, we examined cell viability. We also analyzed nucleosome
      assembly in vivo and in vitro by examining plasmid superhelicity density in whole
      cells and supercoiling in yeast cell extracts. All three approaches demonstrate
      that mutagenizing K5 and K12 together does not prevent cell growth and histone
      deposition in vivo or in vitro. Therefore, K5/K12 cannot be required for
      nucleosome assembly in yeast. It is only when the first three sites of
      acetylation-K5, K8, and K12-are mutagenized simultaneously that lethality occurs
      and assembly is most strongly decreased both in vivo and in vitro. These data
      argue for the redundancy of sites K5, K8, and K12 in the deposition of yeast
      histone H4.

PMID- 9618475
TI  - Control of pre-mRNA accumulation by the essential yeast protein Nrd1 requires
      high-affinity transcript binding and a domain implicated in RNA polymerase II
      association.
AB  - Nrd1 is an essential yeast protein of unknown function that has an RNA
      recognition motif (RRM) in its carboxyl half and a putative RNA polymerase II
      binding domain, the CTD-binding motif, at its amino terminus. Nrd1 mediates a
      severe reduction in pre-mRNA production from a reporter gene bearing an exogenous
      sequence element in its intron. The effect of the inserted element is highly
      sequence-specific and is accompanied by the appearance of 3'-truncated
      transcripts. We have proposed that Nrd1 binds to the exogenous sequence element
      in the nascent pre-mRNA during transcription, aided by the CTD-binding motif, and
      directs 3'-end formation a short distance downstream. Here we show that highly
      purified Nrd1 carboxyl half binds tightly to the RNA element in vitro with
      sequence specificity that correlates with the efficiency of cis-element-directed
      down-regulation in vivo. A large deletion in the CTD-binding motif blocks down
      regulation but does not affect the essential function of Nrd1. Furthermore, a
      nonsense mutant allele that produces truncated Nrd1 protein lacking the RRM has a
      dominant-negative effect on down-regulation but not on cell growth. Viability of
      this and several other nonsense alleles of Nrd1 appears to require translational
      readthrough, which in one case is extremely efficient. Thus the CTD-binding motif
      of Nrd1 is important for pre-mRNA down-regulation but is not required for the
      essential function of Nrd1. In contrast, the RNA-binding activity of Nrd1 appears
      to be required both for down-regulation and for its essential function.

PMID- 9618476
TI  - Expressed protein ligation: a general method for protein engineering.
AB  - A protein semisynthesis method-expressed protein ligation-is described that
      involves the chemoselective addition of a peptide to a recombinant protein. This
      method was used to ligate a phosphotyrosine peptide to the C terminus of the
      protein tyrosine kinase C-terminal Src kinase (Csk). By intercepting a thioester
      generated in the recombinant protein with an N-terminal cysteine containing
      synthetic peptide, near quantitative chemical ligation of the peptide to the
      protein was achieved. The semisynthetic tail-phosphorylated Csk showed evidence
      of an intramolecular phosphotyrosine-Src homology 2 interaction and an unexpected
      increase in catalytic phosphoryl transfer efficiency toward a physiologically
      relevant substrate compared with the non-tail-phosphorylated control. This work
      illustrates that expressed protein ligation is a simple and powerful new method
      in protein engineering to introduce sequences of unnatural amino acids,
      posttranslational modifications, and biophysical probes into proteins of any
      size.

PMID- 9618477
TI  - Thermostable archaeal O6-alkylguanine-DNA alkyltransferases.
AB  - Archaea represent some of the most ancient organisms on earth, and they have
      relatively uncharacterized DNA repair processes. We now show, using an in vitro
      assay, that extracts of two Crenarchaeota (Sulfolobus acidocaldarius and
      Pyrobaculum islandicum) and two Euryarchaeota (Pyrococcus furiosus and
      Thermococcus litoralis) contain the DNA repair protein O6-alkylguanine-DNA
      alkyltransferase (ATase). The ATase activities found in the archaea were
      extremely thermostable, with half-lives at 80 degreesC ranging from 0.5 hr (S.
      acidocaldarius) to 13 hr (T. litoralis). The temperature optima of the four
      proteins ranged from approximately 75 to approximately 100 degreesC, although
      activity was seen at 37 degreesC, the temperature optimum of the Escherichia coli
      and human ATases. In all cases, preincubaton of extracts with a short
      oligonucleotide containing a single O6-methylguanine residue caused essentially
      complete loss of ATase activity, suggesting that the alkylphosphotriester-DNA
      alkyltransferase activity seen in some prokaryotes is not present in Archaea. The
      ATase from Pyrobaculum islandicum had an apparent molecular mass of 15 kDa,
      making it the smallest of these proteins so far described. In higher organisms,
      ATase is responsible for the repair of toxic and mutagenic O6-alkylguanine
      lesions in alkylated DNA. The presence of ATase in these primitive organisms
      therefore suggests that endogenous or exogenous exposure to agents that generate
      appropriate substrates in DNA may be an early event in evolution.

PMID- 9618478
TI  - Rpp2, an essential protein subunit of nuclear RNase P, is required for processing
      of precursor tRNAs and 35S precursor rRNA in Saccharomyces cerevisiae.
AB  - RPP2, an essential gene that encodes a 15.8-kDa protein subunit of nuclear RNase
      P, has been identified in the genome of Saccharomyces cerevisiae. Rpp2 was
      detected by sequence similarity with a human protein, Rpp20, which copurifies
      with human RNase P. Epitope-tagged Rpp2 can be found in association with both
      RNase P and RNase mitochondrial RNA processing in immunoprecipitates from crude
      extracts of cells. Depletion of Rpp2 protein in vivo causes accumulation of
      precursor tRNAs with unprocessed introns and 5' and 3' termini, and leads to
      defects in the processing of the 35S precursor rRNA. Rpp2-depleted cells are
      defective in processing of the 5.8S rRNA. Rpp2 immunoprecipitates cleave both
      yeast precursor tRNAs and precursor rRNAs accurately at the expected sites and
      contain the Rpp1 protein orthologue of the human scleroderma autoimmune antigen,
      Rpp30. These results demonstrate that Rpp2 is a protein subunit of nuclear RNase
      P that is functionally conserved in eukaryotes from yeast to humans.

PMID- 9618479
TI  - An interplay between TATA box-binding protein and transcription factors IIE and
      IIA modulates DNA binding and transcription.
AB  - The basal transcription factor IIE (TFIIE) is thought to be one of the last
      factors to be assembled into a preinitiation complex (PIC) at eukaryotic
      promoters after RNA polymerase II and TFIIF have been incorporated. It was shown
      that a primary function of TFIIE is to recruit and cooperate with TFIIH in
      promoter melting. Here, we show that the large subunit of TFIIE (E56) can
      directly stimulate TBP binding to the promoter in the absence of other basal
      factors. The zinc-finger domain of E56, required for transcriptional activity, is
      critical for this function. In addition, the small subunit of TFIIE (E34)
      directly contacts DNA and TFIIA and thus providing a second mechanism for TFIIE
      to help binding of a TBP/IIA complex to the promoter, the first critical step in
      the PIC assembly. These studies suggest an alternative PIC assembly pathway in
      which TFIIE affects both TBP and TFIIH functions during initiation of RNA
      synthesis.

PMID- 9618480
TI  - Two-domain reconstitution of a functional protein histidine kinase.
AB  - In prokaryotes, in the absence of protein serine/threonine/tyrosine kinases,
      protein histidine kinases play a major role in signal transduction involved in
      cellular adaptation to various environmental changes and stresses. Histidine
      kinases phosphorylate their cognate response regulators at a specific aspartic
      acid residue with ATP in response to particular environmental signals. In this
      His-Asp phosphorelay signal transduction system, it is still unknown how the
      histidine kinase exerts its enzymatic function. Here we demonstrate that the
      cytoplasmic kinase domain of EnvZ, a transmembrane osmosensor of Escherichia coli
      can be further divided into two distinct functional subdomains: subdomain A
      [EnvZ(C). (223-289); 67 residues] and subdomain B [EnvZ(C).(290-450); 161
      residues]. Subdomain A, with a high helical content, contains the
      autophosphorylation site, H-243, and forms a stable dimer having the recognition
      site for OmpR, the cognate response regulator of EnvZ. Subdomain B, an alpha/beta
      protein, exists as a monomer. When mixed, the two subdomains reconstitute the
      kinase function to phosphorylate subdomain A at His-243 in the presence of ATP.
      Subsequently, the phosphorylated subdomain A is able to transfer its phosphate
      group to OmpR. The two-domain structure of this histidine kinase provides an
      insight into the structural arrangement of the enzyme and its
      transphosphorylation mechanism.

PMID- 9618481
TI  - Regulation of the human p21/WAF1/Cip1 promoter in hepatic cells by functional
      interactions between Sp1 and Smad family members.
AB  - The cell cycle inhibitor p21/WAF1/Cip1 is expressed in many cell types and is
      regulated by p53-dependent and p53-independent mechanisms. p21 is an important
      regulator of hepatocyte cell cycle, differentiation, and liver development, but
      little is known about the regulation of its synthesis in hepatocytes. We report
      herein that the p21 gene is constitutively expressed in human hepatoma HepG2
      cells. Deletion analysis of the p21 promoter showed that it contains a distal
      (positions -2,300/-210) and a proximal (positions -124 to -61) region that act
      synergistically to achieve high levels of constitutive expression. The proximal
      region that consists of multiple Sp1 binding sites is essential for constitutive
      p21 promoter activity in hepatocytes. This region also mediates the
      transcriptional activation of the p21 promoter by members of the Smad family of
      proteins, which play important role in the transduction of extracellular signals
      such as transforming growth factor beta, activin, etc. Constitutive expression of
      p21 was severely reduced by a C-terminally truncated form of Smad4 that was shown
      previously to block signaling through Smads. Smad3/4 and to a much lesser extent
      Smad2/4 caused high levels of transcriptional activation of the p21 promoter.
      Transactivation was compromised by N- or C-terminally truncated forms of Smad3.
      By using Gal4-Sp1 fusion proteins, we show that Smad proteins can activate gene
      transcription via functional interactions with the ubiquitous factor Sp1. These
      data demonstrate that Smad proteins and Sp1 participate in the constitutive or
      inducible expression of the p21 gene in hepatic cells.

PMID- 9618482
TI  - The high mobility group protein Abf2p influences the level of yeast mitochondrial
      DNA recombination intermediates in vivo.
AB  - Abf2p is a high mobility group (HMG) protein found in yeast mitochondria that is
      required for the maintenance of wild-type (rho+) mtDNA in cells grown on
      fermentable carbon sources, and for efficient recombination of mtDNA markers in
      crosses. Here, we show by two-dimensional gel electrophoresis that Abf2p promotes
      or stabilizes Holliday recombination junction intermediates in rho+ mtDNA in vivo
      but does not influence the high levels of recombination intermediates readily
      detected in the mtDNA of petite mutants (rho-). mtDNA recombination junctions are
      not observed in rho+ mtDNA of wild-type cells but are elevated to detectable
      levels in cells with a null allele of the MGT1 gene (Deltamgt1), which codes for
      a mitochondrial cruciform-cutting endonuclease. The level of recombination
      intermediates in rho+ mtDNA of Deltamgt1 cells is decreased about 10-fold if
      those cells contain a null allele of the ABF2 gene. Overproduction of Abf2p by
      >/= 10-fold in wild-type rho+ cells, which leads to mtDNA instability, results in
      a dramatic increase in mtDNA recombination intermediates. Specific mutations in
      the two Abf2p HMG boxes required for DNA binding diminishes these responses. We
      conclude that Abf2p functions in the recombination of rho+ mtDNA.

PMID- 9618483
TI  - A 12R-lipoxygenase in human skin: mechanistic evidence, molecular cloning, and
      expression.
AB  - A recognized feature of psoriasis and other proliferative dermatoses is
      accumulation in the skin of the unusual arachidonic acid metabolite, 12R
      hydroxyeicosatetraenoic acid (12R-HETE). This hydroxy fatty acid is opposite in
      chirality to the product of the well-known 12S-lipoxygenase and heretofore in
      mammals is known only as a product of cytochrome P450s. Here we provide
      mechanistic evidence for a lipoxygenase route to 12R-HETE in human psoriatic
      tissue and describe a 12R-lipoxygenase that can account for the biosynthesis.
      Initially we demonstrated retention of the C-12 deuterium of octadeuterated
      arachidonic acid in its conversion to 12R-HETE in incubations of psoriatic
      scales, indicating the end product is not formed by isomerization from 12S
      H(P)ETE via the 12-keto derivative. Secondly, analysis of product formed from
      [10R-3H] and [10S-3H]-labeled arachidonic acids revealed that 12R-HETE synthesis
      is associated with stereospecific removal of the pro-R hydrogen from the 10
      carbon of arachidonate. This result is compatible with 12R-lipoxygenase-catalyzed
      formation of 12R-HETE and not with a P450-catalyzed route to 12R-HETE in
      psoriatic scales. We cloned a lipoxygenase from human keratinocytes; the cDNA and
      deduced amino acid sequences share </=50% identity to other human lipoxygenases.
      This enzyme, when expressed in Hela cells, oxygenates arachidonic acid to 12
      HPETE, >98% 12R in configuration. The 12R-lipoxygenase cDNA is detectable by PCR
      in psoriatic scales and as a 2.5-kilobase mRNA by Northern analysis of
      keratinocytes. Identification of this enzyme extends the known distribution of R
      lipoxygenases to humans and presents an additional target for potential
      therapeutic interventions in psoriasis.

PMID- 9618484
TI  - Quantitative modeling of stochastic systems in molecular biology by using
      stochastic Petri nets.
AB  - An integrated understanding of molecular and developmental biology must consider
      the large number of molecular species involved and the low concentrations of many
      species in vivo. Quantitative stochastic models of molecular interaction networks
      can be expressed as stochastic Petri nets (SPNs), a mathematical formalism
      developed in computer science. Existing software can be used to define molecular
      interaction networks as SPNs and solve such models for the probability
      distributions of molecular species. This approach allows biologists to focus on
      the content of models and their interpretation, rather than their implementation.
      The standardized format of SPNs also facilitates the replication, extension, and
      transfer of models between researchers. A simple chemical system is presented to
      demonstrate the link between stochastic models of molecular interactions and
      SPNs. The approach is illustrated with examples of models of genetic and
      biochemical phenomena where the ULTRASAN package is used to present results from
      numerical analysis and the outcome of simulations.

PMID- 9618486
TI  - Structural factors controlling ligand binding to myoglobin: a kinetic hole
      burning study.
AB  - Using temperature-derivative spectroscopy in the temperature range below 100 K,
      we have studied the dependence of the Soret band on the recombination barrier in
      sperm whale carbonmonoxy myoglobin (MbCO) after photodissociation at 12 K. The
      spectra were separated into contributions from the photodissociated species,
      Mb*CO, and CO-bound myoglobin. The line shapes of the Soret bands of both
      photolyzed and liganded myoglobin were analyzed with a model that takes into
      account the homogeneous bandwidth, coupling of the electronic transition to
      vibrational modes, and static conformational heterogeneity. The analysis yields
      correlations between the activation enthalpy for rebinding and the model
      parameters that characterize the homogeneous subensembles within the
      conformationally heterogeneous ensemble. Such couplings between spectral and
      functional parameters arise when they both originate from a common structural
      coordinate. This effect is frequently denoted as "kinetic hole burning." The
      study of these correlations gives direct insights into the structure-function
      relationship in proteins. On the basis of earlier work that assigned spectral
      parameters to geometric properties of the heme, the connections with the heme
      geometry are discussed. We show that two separate structural coordinates
      influence the Soret line shape, but only one of the two is coupled to the
      enthalpy barrier for rebinding. We give evidence that this coordinate, contrary
      to widespread belief, is not the iron displacement from the mean heme plane.

PMID- 9618485
TI  - Terpenoid-based defenses in conifers: cDNA cloning, characterization, and
      functional expression of wound-inducible (E)-alpha-bisabolene synthase from grand
      fir (Abies grandis).
AB  - (E)-alpha-Bisabolene synthase is one of two wound-inducible sesquiterpene
      synthases of grand fir (Abies grandis), and the olefin product of this
      cyclization reaction is considered to be the precursor in Abies species of
      todomatuic acid, juvabione, and related insect juvenile hormone mimics. A cDNA
      encoding (E)-alpha-bisabolene synthase was isolated from a wound-induced grand
      fir stem library by a PCR-based strategy and was functionally expressed in
      Escherichia coli and shown to produce (E)-alpha-bisabolene as the sole product
      from farnesyl diphosphate. The expressed synthase has a deduced size of 93.8 kDa
      and a pI of 5. 03, exhibits other properties typical of sesquiterpene synthases,
      and resembles in sequence other terpenoid synthases with the exception of a large
      amino-terminal insertion corresponding to Pro81-Val296. Biosynthetically prepared
      (E)-alpha-[3H]bisabolene was converted to todomatuic acid in induced grand fir
      cells, and the time course of appearance of bisabolene synthase mRNA was shown by
      Northern hybridization to lag behind that of mRNAs responsible for production of
      induced oleoresin monoterpenes. These results suggest that induced (E)-alpha
      bisabolene biosynthesis constitutes part of a defense response targeted to insect
      herbivores, and possibly fungal pathogens, that is distinct from induced
      oleoresin monoterpene production.

PMID- 9618487
TI  - Crystal structure of 2,5-diketo-D-gluconic acid reductase A complexed with NADPH
      at 2.1-A resolution.
AB  - The three-dimensional structure of Corynebacterium 2, 5-diketo-D-gluconic acid
      reductase A (2,5-DKGR A; EC 1.1.1.-), in complex with cofactor NADPH, has been
      solved by using x-ray crystallographic data to 2.1-A resolution. This enzyme
      catalyzes stereospecific reduction of 2,5-diketo-D-gluconate (2,5-DKG) to 2-keto
      L-gulonate. Thus the three-dimensional structure has now been solved for a
      prokaryotic example of the aldo-keto reductase superfamily. The details of the
      binding of the NADPH cofactor help to explain why 2,5-DKGR exhibits lower binding
      affinity for cofactor than the related human aldose reductase does. Furthermore,
      changes in the local loop structure near the cofactor suggest that 2,5-DKGR will
      not exhibit the biphasic cofactor binding characteristics observed in aldose
      reductase. Although the crystal structure does not include substrate, the two
      ordered water molecules present within the substrate-binding pocket are
      postulated to provide positional landmarks for the substrate 5-keto and 4
      hydroxyl groups. The structural basis for several previously described active
      site mutants of 2,5-DKGR A is also proposed. Recent research efforts have
      described a novel approach to the synthesis of L-ascorbate (vitamin C) by using a
      genetically engineered microorganism that is capable of synthesizing 2,5-DKG from
      glucose and subsequently is transformed with the gene for 2,5-DKGR. These
      modifications create a microorganism capable of direct production of 2-keto-L
      gulonate from D-glucose, and the gulonate can subsequently be converted into
      vitamin C. In economic terms, vitamin C is the single most important specialty
      chemical manufactured in the world. Understanding the structural determinants of
      specificity, catalysis, and stability for 2,5-DKGR A is of substantial commercial
      interest.

PMID- 9618488
TI  - Antiviral agent blocks breathing of the common cold virus.
AB  - A dynamic capsid is critical to the events that shape the viral life cycle;
      events such as cell attachment, cell entry, and nucleic acid release demand a
      highly mobile viral surface. Protein mass mapping of the common cold virus, human
      rhinovirus 14 (HRV14), revealed both viral structural dynamics and the inhibition
      of such dynamics with an antiviral agent, WIN 52084. Viral capsid digestion
      fragments resulting from proteolytic time-course experiments provided structural
      information in good agreement with the HRV14 three-dimensional crystal structure.
      As expected, initial digestion fragments included peptides from the capsid
      protein VP1. This observation was expected because VP1 is the most external viral
      protein. Initial digestion fragments also included peptides belonging to VP4, the
      most internal capsid protein. The mass spectral results together with x-ray
      crystallography data provide information consistent with a "breathing" model of
      the viral capsid. Whereas the crystal structure of HRV14 shows VP4 to be the most
      internal capsid protein, mass spectral results show VP4 fragments to be among the
      first digestion fragments observed. Taken together this information demonstrates
      that VP4 is transiently exposed to the viral surface via viral breathing.
      Comparative digests of HRV14 in the presence and absence of WIN 52084 revealed a
      dramatic inhibition of digestion. These results indicate that the binding of the
      antiviral agent not only causes local conformational changes in the drug binding
      pocket but actually stabilizes the entire viral capsid against enzymatic
      degradation. Viral capsid mass mapping provides a fast and sensitive method for
      probing viral structural dynamics as well as providing a means for investigating
      antiviral drug efficacy.

PMID- 9618489
TI  - The human homologue of Saccharomyces cerevisiae Gle1p is required for poly(A)+
      RNA export.
AB  - The mechanism of mRNA export is a complex issue central to cellular physiology.
      We characterized previously yeast Gle1p, a protein with a leucine-rich (LR)
      nuclear export sequence (NES) that is essential for poly(A)+ RNA export in
      Saccharomyces cerevisiae. To characterize elements of the vertebrate mRNA export
      pathway, we identified a human homologue of yeast Gle1p and analyzed its function
      in mammalian cells. hGLE1 encodes a predicted 75-kDa polypeptide with high
      sequence homology to yeast Gle1p, but hGle1p does not contain a sequence motif
      matching any of the previously characterized NESs. hGLE1 can complement a yeast
      gle1 temperature-sensitive export mutant only if a LR-NES is inserted into it. To
      determine whether hGle1p played a role in nuclear export, anti-hGle1p antibodies
      were microinjected into HeLa cells. In situ hybridization of injected cells
      showed that poly(A)+ RNA export was inhibited. In contrast, there was no effect
      on the nuclear import of a glucocorticoid receptor reporter. We conclude that
      hGle1p functions in poly(A)+ RNA export, and that human cells facilitate such
      export with a factor similar to yeast but without a recognizable LR-NES. With
      hGle1p localized at the nuclear pore complexes, hGle1p is positioned to act at a
      terminal step in the export of mature RNA messages to the cytoplasm.

PMID- 9618490
TI  - Caspase-dependent activation of cyclin-dependent kinases during Fas-induced
      apoptosis in Jurkat cells.
AB  - The activation of cyclin-dependent kinases (cdks) has been implicated in
      apoptosis induced by various stimuli. We find that the Fas-induced activation of
      cdc2 and cdk2 in Jurkat cells is not dependent on protein synthesis, which is
      shut down very early during apoptosis before caspase-3 activation. Instead,
      activation of these kinases seems to result from both a rapid cleavage of Wee1
      (an inhibitory kinase of cdc2 and cdk2) and inactivation of anaphase-promoting
      complex (the specific system for cyclin degradation), in which CDC27 homolog is
      cleaved during apoptosis. Both Wee1 and CDC27 are shown to be substrates of the
      caspase-3-like protease. Although cdk activities are elevated during Fas-induced
      apoptosis in Jurkat cells, general activation of the mitotic processes does not
      occur. Our results do not support the idea that apoptosis is simply an aberrant
      mitosis but, instead, suggest that a subset of mitotic mechanisms plays an
      important role in apoptosis through elevated cdk activities.

PMID- 9618491
TI  - p21(WAF1) is required for butyrate-mediated growth inhibition of human colon
      cancer cells.
AB  - A diet high in fiber is associated with a decreased incidence and growth of colon
      cancers. Butyrate, a four-carbon short-chain fatty acid product of fiber
      fermentation within the colon, appears to mediate these salutary effects. We
      sought to determine the molecular mechanism by which butyrate mediates growth
      inhibition of colonic cancer cells and thereby to elucidate the molecular link
      between a high-fiber diet and the arrest of colon carcinogenesis. We show that
      concomitant with growth arrest, butyrate induces p21 mRNA expression in an
      immediate-early fashion, through transactivation of a promoter cis-element(s)
      located within 1.4 kb of the transcriptional start site, independent of p53
      binding. Studies using the specific histone hyperacetylating agent, trichostatin
      A, and histone deacetylase 1 indicate that growth arrest and p21 induction occur
      through a mechanism involving histone hyperacetylation. We show the critical
      importance of p21 in butyrate-mediated growth arrest by first confirming that
      stable overexpression of the p21 gene is able to cause growth arrest in the human
      colon carcinoma cell line, HT-29. Furthermore, using p21-deleted HCT116 human
      colon carcinoma cells, we provide convincing evidence that p21 is required for
      growth arrest to occur in response to histone hyperacetylation, but not for serum
      starvation nor postconfluent growth. Thus, p21 appears to be a critical effector
      of butyrate-induced growth arrest in colonic cancer cells, and may be an
      important molecular link between a high-fiber diet and the prevention of colon
      carcinogenesis.

PMID- 9618492
TI  - Static and dynamic lengths of neutrophil microvilli.
AB  - Containing most of the L-selectin and P-selectin glycoprotein ligand-1 (PSGL-1)
      on their tips, microvilli are believed to promote the initial arrest of
      neutrophils on endothelium. At the rolling stage following arrest, the lifetimes
      of the involved molecular bonds depend on the pulling force imposed by the shear
      stress of blood flow. With two different methods, electron microscopy and
      micropipette manipulation, we have obtained two comparable neutrophil microvillus
      lengths, both approximately 0.3 microm in average. We have found also that, under
      a pulling force, a microvillus can be extended (microvillus extension) or a long
      thin membrane cylinder (a tether) can be formed from it (tether formation). If
      the force is </=34 pN (+/- 3 pN), the length of the microvillus will be extended;
      if the force is >61 pN (+/- 5 pN), a tether will be formed from the microvillus
      at a constant velocity, which depends linearly on the force. When the force is
      between 34 pN and 61 pN (transition zone), the degree of association between
      membrane and cytoskeleton in individual microvilli will dictate whether
      microvillus extension or tether formation occurs. When a microvillus is extended,
      it acts like a spring with a spring constant of approximately 43 pN/microm. In
      contrast to a rigid or nonextendible microvillus, both microvillus extension and
      tether formation can decrease the pulling force imposed on the adhesive bonds,
      and thus prolonging the persistence of the bonds at high physiological shear
      stresses.

PMID- 9618493
TI  - Measurement of cytosolic, mitochondrial, and Golgi pH in single living cells with
      green fluorescent proteins.
AB  - Many cellular events depend on a tightly compartmentalized distribution of H+
      ions across membrane-bound organelles. However, measurements of organelle pH in
      living cells have been scarce. Several mutants of the Aequorea victoria green
      fluorescent protein (GFP) displayed a pH-dependent absorbance and fluorescent
      emission, with apparent pKa values ranging from 6.15 (mutations F64L/S65T/H231L)
      and 6.4 (K26R/F64L/S65T/Y66W/N146I/M153T/ V163A/N164H/H231L) to a remarkable 7.1
      (S65G/S72A/T203Y/H231L). We have targeted these GFPs to the cytosol plus nucleus,
      the medial/trans-Golgi by fusion with galactosyltransferase, and the
      mitochondrial matrix by using the targeting signal from subunit IV of cytochrome
      c oxidase. Cells in culture transfected with these cDNAs displayed the expected
      subcellular localization by light and electron microscopy and reported local pH
      that was calibrated in situ with ionophores. We monitored cytosolic and nuclear
      pH of HeLa cells, and mitochondrial matrix pH in HeLa cells and in rat neonatal
      cardiomyocytes. The pH of the medial/trans-Golgi was measured at steady-state
      (calibrated to be 6.58 in HeLa cells) and after various manipulations. These
      demonstrated that the Golgi membrane in intact cells is relatively permeable to
      H+, and that Cl- serves as a counter-ion for H+ transport and likely helps to
      maintain electroneutrality. The amenability to engineer GFPs to specific
      subcellular locations or tissue targets using gene fusion and transfer techniques
      should allow us to examine pH at sites previously inaccessible.

PMID- 9618494
TI  - ErbB2 expression increases the spectrum and potency of ligand-mediated signal
      transduction through ErbB4.
AB  - Interleukin 3-dependent murine 32D cells do not detectably express members of the
      ErbB receptor family and do not proliferate in response to known ligands for
      these receptors. 32D transfectants were generated expressing human ErbB4 alone
      (32D.E4) or with ErbB2 (32D.E2/E4). Epidermal growth factor (EGF), neuregulin 1
      beta (NRG1-beta), betacellulin (BTC), transforming growth factor-alpha (TGF
      alpha), heparin binding-EGF (HB-EGF), and amphiregulin were analyzed for their
      ability to mediate mitogenesis in these transfectants. 32D.E4 responded
      mitogenically to NRG1-beta and BTC. Surprisingly, EGF also induced significant
      DNA synthesis and TGF-alpha was negligibly mitogenic on 32D.E4 cells, whereas HB
      EGF and amphiregulin were inactive. Although coexpression of ErbB2 with ErbB4 in
      32D.E2/E4 cells did not significantly alter DNA synthesis in response to NRG1
      beta or BTC, it greatly enhanced mitogenesis elicited by EGF and TGF-alpha and
      unmasked the ability of HB-EGF to induce proliferation. EGF-related ligands that
      exhibited potent mitogenic activity on 32D.E2/E4 cells at low concentrations
      induced adherence, morphological alterations, and up-regulation of the Mac-1
      integrin and FcgammaRII/III at higher concentrations. While 125I-EGF could be
      specifically crosslinked to both 32D.E4 and 32D.E2/E4 cells, its crosslinking
      capacity was greatly enhanced in the cotransfected cells. The ability of the
      various ligands to mediate proliferation and/or adhesion in the two transfectants
      correlated with their capacity to induce substrate tyrosine phosphorylation and
      to initiate and sustain activation of mitogen-activated protein kinase. We
      conclude that the ability of ErbB4 to mediate signal transduction through EGF
      like ligands is broader than previously assumed and can be profoundly altered by
      the concomitant expression of ErbB2.

PMID- 9618495
TI  - Endothelin-induced conversion of embryonic heart muscle cells into impulse
      conducting Purkinje fibers.
AB  - A regular heart beat is dependent on a specialized network of pacemaking and
      conductive cells. There has been a longstanding controversy regarding the
      developmental origin of these cardiac tissues which also manifest neural-like
      properties. Recently, we have shown conclusively that during chicken
      embryogenesis, impulse-conducting Purkinje cells are recruited from myocytes in
      spatial association with developing coronary arteries. Here, we report that
      cultured embryonic myocytes convert to a Purkinje cell phenotype after exposure
      to the vascular cytokine, endothelin. This inductive response declined gradually
      during development. These results yield further evidence for a role of
      arteriogenesis in the induction of impulse-conducting Purkinje cells within the
      heart muscle lineage and also may provide a basis for tissue engineering of
      cardiac pacemaking and conductive cells.

PMID- 9618496
TI  - The gastrulation defective gene of Drosophila melanogaster is a member of the
      serine protease superfamily.
AB  - The establishment of dorsal-ventral polarity in the oocyte involves two sets of
      genes. One set belongs to the gurken-torpedo signaling pathway and affects the
      development of the egg chorion as well as the polarity of the embryo. The second
      set of genes affects only the dorsal-ventral polarity of the embryo but not the
      eggshell. gastrulation defective is one of the earliest acting of this second set
      of maternally required genes. We have cloned and characterized the gastrulation
      defective gene and determined that it encodes a protein structurally related to
      the serine protease superfamily, which also includes the Snake, Easter, and Nudel
      proteins. These data provide additional support for the involvement of a protease
      cascade in generating an asymmetric signal (i.e., asymmetric Spatzle activity)
      during establishment of dorsal-ventral polarity in the Drosophila embryo.

PMID- 9618497
TI  - Molecular cloning and characterization of an invertebrate cellular retinoic acid
      binding protein.
AB  - We have cloned a cDNA and gene from the tobacco hornworm, Manduca sexta, which is
      related to the vertebrate cellular retinoic acid binding proteins (CRABPs).
      CRABPs are members of the superfamily of lipid binding proteins (LBPs) and are
      thought to mediate the effects of retinoic acid (RA) on morphogenesis,
      differentiation, and homeostasis. This discovery of a Manduca sexta CRABP
      (msCRABP) demonstrates the presence of a CRABP in invertebrates. Compared with
      bovine/murine CRABP I, the deduced amino acid sequence of msCRABP is 71%
      homologous overall and 88% homologous for the ligand binding pocket. The genomic
      organization of msCRABP is conserved with other CRABP family members and the
      larger LBP superfamily. Importantly, the promoter region contains a motif that
      resembles an RA response element characteristic of the promoter region of most
      CRABPs analyzed. Three-dimensional molecular modeling based on postulated
      structural homology with bovine/murine CRABP I shows msCRABP has a ligand binding
      pocket that can accommodate RA. The existence of an invertebrate CRABP has
      significant evolutionary implications, suggesting CRABPs appeared during the
      evolution of the LBP superfamily well before vertebrate/invertebrate divergence,
      instead of much later in evolution in selected vertebrates.

PMID- 9618499
TI  - Aggregate community properties and the strength of species' interactions.
AB  - Although humanity depends on the continued, aggregate functioning of natural
      ecosystems, few studies have explored the impact of community structure on the
      stability of aggregate community properties. Here we derive the stability of the
      aggregate property of community biomass as a function of species' competition
      coefficients for a two-species model. The model predicts that the stability of
      community biomass is relatively independent of the magnitude of the interaction
      strengths. Instead, the degree of asymmetry of the interactions appears to be key
      to community stability.

PMID- 9618498
TI  - Cross-lineage expression of Ig-beta (B29) in thymocytes: positive and negative
      gene regulation to establish T cell identity.
AB  - Developmental commitment involves activation of lineage-specific genes,
      stabilization of a lineage-specific gene expression program, and permanent
      inhibition of inappropriate characteristics. To determine how these processes are
      coordinated in early T cell development, the expression of T and B lineage
      specific genes was assessed in staged subsets of immature thymocytes. T lineage
      characteristics are acquired sequentially, with germ-line T cell antigen receptor
      beta transcripts detected very early, followed by CD3epsilon and terminal
      deoxynucleotidyl transferase, then pTalpha, and finally RAG1. Only RAG1
      expression coincides with commitment. Thus, much T lineage gene expression
      precedes commitment and does not depend on it. Early in the course of commitment
      to the T lineage, thymocytes lose the ability to develop into B cells. To
      understand how this occurs, we also examined expression of well defined B lineage
      specific genes. Although lambda5 and Ig-alpha are not expressed, the mu 0 and I
      mu transcripts from the unrearranged IgH locus are expressed early, in distinct
      patterns, then repressed just before RAG1 expression. By contrast, RNA encoding
      the B cell receptor component Ig-beta was found to be transcribed in all immature
      thymocyte subpopulations and throughout most thymocyte differentiation. Ig-beta
      expression is down-regulated only during positive selection of CD4(+)CD8(-)
      cells. Thus several key participants in the B cell developmental program are
      expressed in non-B lineage-committed cells, and one is maintained even through
      commitment to an alternative lineage, and repressed only after extensive T
      lineage differentiation. The results show that transcriptional activation of
      "lymphocyte-specific" genes can occur in uncommitted precursors, and that T
      lineage commitment is a composite of distinct positive and negative regulatory
      events.

PMID- 9618500
TI  - Variation in per capita interaction strength: thresholds due to nonlinear
      dynamics and nonequilibrium conditions.
AB  - I measured the strength of interaction between a marine herbivore and its growing
      resource over a realistic range of absolute and relative abundances. The
      herbivores (hermit crabs: Pagurus spp.) have slow and/or weak functional and
      numerical responses to epiphytic diatoms (Isthmia nervosa), which show logistic
      growth in the absence of consumers. By isolating this interaction in containers
      in the field, I mimicked many of the physical and biological variables
      characteristic of the intertidal while controlling the densities of focal
      species. The per capita effects of consumers on the population dynamics of their
      resource (i.e., interaction strength) were defined by using the relationship
      between hermit crab density and proportional change in the resource. When this
      relationship is fit by a Weibull function, a single parameter distinguishes
      constant interaction strength from one that varies as a function of density.
      Constant interaction strength causes the proportion of diatoms to fall linearly
      or proportionally as hermit crab density increases whereas per capita effects
      that increase with density cause an accelerating decline. Although many
      mathematical models of species interactions assume linear dynamics and invariant
      parameters, at least near equilibrium, the per capita effects of hermit crabs on
      diatoms varied substantially, apparently crossing a threshold from weak to strong
      when consumption exceeded resource production. This threshold separates a domain
      of coexistence from one of local extinction of the resource. Such thresholds may
      help explain trophic cascades, resource compensation, and context-dependent
      interaction strengths, while indicating a way to predict trophic effects, despite
      nonlinearities, as a function of vital rates.

PMID- 9618501
TI  - Amyrel, a paralogous gene of the amylase gene family in Drosophila melanogaster
      and the Sophophora subgenus.
AB  - We describe a gene from Drosophila melanogaster related to the alpha-amylase gene
      Amy. This gene, which exists as a single copy, was named Amyrel. It is strikingly
      divergent from Amy because the amino acid divergence is 40%. The coding sequence
      is interrupted by a short intron at position 655, which is unusual in amylase
      genes. Amyrel has also been cloned in Drosophila ananassae, Drosophila
      pseudoobscura, and Drosophila subobscura and is likely to be present throughout
      the Sophophora subgenus, but, to our knowledge, it has not been detected outside.
      Unexpectedly, there is a strong conservation of 5' and 3' flanking regions
      between Amyrel genes from different species, which is not the case for Amy and
      which suggests that selection acts on these regions. In contrast to the Amy
      genes, Amyrel is transcribed in larvae of D. melanogaster but not in adults.
      However, the protein has not been detected yet. Amyrel evolves about twice as
      fast as Amy in the several species studied. We suggest that this gene could
      result from a duplication of Amy followed by accelerated and selected divergence
      toward a new adaptation.

PMID- 9618502
TI  - The universal ancestor.
AB  - A genetic annealing model for the universal ancestor of all extant life is
      presented; the name of the model derives from its resemblance to physical
      annealing. The scenario pictured starts when "genetic temperatures" were very
      high, cellular entities (progenotes) were very simple, and information processing
      systems were inaccurate. Initially, both mutation rate and lateral gene transfer
      levels were elevated. The latter was pandemic and pervasive to the extent that
      it, not vertical inheritance, defined the evolutionary dynamic. As increasingly
      complex and precise biological structures and processes evolved, both the
      mutation rate and the scope and level of lateral gene transfer, i.e.,
      evolutionary temperature, dropped, and the evolutionary dynamic gradually became
      that characteristic of modern cells. The various subsystems of the cell
      "crystallized," i.e., became refractory to lateral gene transfer, at different
      stages of "cooling," with the translation apparatus probably crystallizing first.
      Organismal lineages, and so organisms as we know them, did not exist at these
      early stages. The universal phylogenetic tree, therefore, is not an organismal
      tree at its base but gradually becomes one as its peripheral branchings emerge.
      The universal ancestor is not a discrete entity. It is, rather, a diverse
      community of cells that survives and evolves as a biological unit. This communal
      ancestor has a physical history but not a genealogical one. Over time, this
      ancestor refined into a smaller number of increasingly complex cell types with
      the ancestors of the three primary groupings of organisms arising as a result.

PMID- 9618503
TI  - Secondary absence of mitochondria in Giardia lamblia and Trichomonas vaginalis
      revealed by valyl-tRNA synthetase phylogeny.
AB  - Nuclear-coded valyl-tRNA synthetase (ValRS) of eukaryotes is regarded of
      mitochondrial origin. Complete ValRS sequences obtained by us from two
      amitochondriate protists, the diplomonad, Giardia lamblia and the parabasalid,
      Trichomonas vaginalis were of the eukaryotic type, strongly suggesting an
      identical history of ValRS in all eukaryotes studied so far. The findings
      indicate that diplomonads are secondarily amitochondriate and give further
      evidence for such conclusion reached recently concerning parabasalids. Together
      with similar findings on other amitochondriate groups (microsporidia and
      entamoebids), this work provides critical support for the emerging notion that no
      representatives of the premitochondrial stage of eukaryotic phylogenesis exist
      among the species living today.

PMID- 9618504
TI  - Parenting and survival in anthropoid primates: caretakers live longer.
AB  - Most anthropoid primates are slow to develop, their offspring are mostly single
      births, and the interbirth intervals are long. To maintain a stable population,
      parents must live long enough to sustain the serial production of a sufficient
      number of young to replace themselves while allowing for the death of offspring
      before they can reproduce. However, in many species there is a large differential
      between the sexes in the care provided to offspring. Therefore, we hypothesize
      that in slowly developing species with single births, the sex that bears the
      greater burden in the care of offspring will tend to survive longer. Males are
      incapable of gestating infants and lactating, but in several species fathers
      carry their offspring for long periods. We predict that females tend to live
      longer than males in the species where the mother does most or all of the care of
      offspring, that there is no difference in survival between the sexes in species
      in which both parents participate about equally in infant care, and that in the
      species where the father does a greater amount of care than the mother, males
      tend to live longer. The hypothesis is supported by survival data for males and
      females in anthropoid primate species.

PMID- 9618505
TI  - Incidence and functional consequences of hMLH1 promoter hypermethylation in
      colorectal carcinoma.
AB  - Inactivation of the genes involved in DNA mismatch repair is associated with
      microsatellite instability (MSI) in colorectal cancer. We report that
      hypermethylation of the 5' CpG island of hMLH1 is found in the majority of
      sporadic primary colorectal cancers with MSI, and that this methylation was
      often, but not invariably, associated with loss of hMLH1 protein expression. Such
      methylation also occurred, but was less common, in MSI- tumors, as well as in
      MSI+ tumors with known mutations of a mismatch repair gene (MMR). No
      hypermethylation of hMSH2 was found. Hypermethylation of colorectal cancer cell
      lines with MSI also was frequently observed, and in such cases, reversal of the
      methylation with 5-aza-2'-deoxycytidine not only resulted in reexpression of
      hMLH1 protein, but also in restoration of the MMR capacity in MMR-deficient cell
      lines. Our results suggest that microsatellite instability in sporadic colorectal
      cancer often results from epigenetic inactivation of hMLH1 in association with
      DNA methylation.

PMID- 9618506
TI  - A human homolog of the Saccharomyces cerevisiae REV3 gene, which encodes the
      catalytic subunit of DNA polymerase zeta.
AB  - To get a better understanding of mutagenic mechanisms in humans, we have cloned
      and sequenced the human homolog of the Saccharomyces cerevisiae REV3 gene. The
      yeast gene encodes the catalytic subunit of DNA polymerase zeta, a nonessential
      enzyme that is thought to carry out translesion replication and is responsible
      for virtually all DNA damage-induced mutagenesis and the majority of spontaneous
      mutagenesis. The human gene encodes an expected protein of 3,130 residues, about
      twice the size of the yeast protein (1,504 aa). The two proteins are 29%
      identical in an amino-terminal region of approximately 340 residues, 39%
      identical in a carboxyl-terminal region of approximately 850 residues, and 29%
      identical in a 55-residue region in the middle of the two genes. The sequence of
      the expected protein strongly predicts that it is the catalytic subunit of a DNA
      polymerase of the pol zeta type; the carboxyl-terminal domain possesses, in the
      right order, the six motifs characteristic of eukaryotic DNA polymerases, most
      closely resembles yeast pol zeta among all polymerases in the GenBank database,
      and is different from the human alpha, delta, and epsilon enzymes. Human cells
      expressing high levels of an hsREV3 antisense RNA fragment grow normally, but
      show little or no UV-induced mutagenesis and are slightly more sensitive to
      killing by UV. The human gene therefore appears to carry out a function similar
      to that of its yeast counterpart.

PMID- 9618507
TI  - SEK1 deficiency reveals mitogen-activated protein kinase cascade crossregulation
      and leads to abnormal hepatogenesis.
AB  - SEK1 (MKK4/JNKK) is a mitogen-activated protein kinase activator that has been
      shown to participate in vitro in two stress-activated cascades terminating with
      the SAPK and p38 kinases. To define the role of SEK1 in vivo, we studied stress
      induced signaling in SEK1(-/-) embryonic stem and fibroblast cells and evaluated
      the phenotype of SEK1(-/-) mouse embryos during development. Studies of SEK1(-/-)
      embryonic stem cells demonstrated defects in stimulated SAPK phosphorylation but
      not in the phosphorylation of p38 kinase. In contrast, SEK1(-/-) fibroblasts
      exhibited defects in both SAPK and p38 phosphorylation, demonstrating that
      crosstalk exists between the stress-activated cascades. Tumor necrosis factor
      alpha and interleukin 1 stimulation of both stress-activated cascades are
      severely affected in the SEK1(-/-) fibroblast cells. SEK1 deficiency leads to
      embryonic lethality after embryonic day 12.5 and is associated with abnormal
      liver development. This phenotype is similar to c-jun null mouse embryos and
      suggests that SEK1 is required for phosphorylation and activation of c-jun during
      the organo-genesis of the liver.

PMID- 9618508
TI  - Nucleolar localization of the Werner syndrome protein in human cells.
AB  - Werner Syndrome (WS) is a human genetic disorder with many features of premature
      aging. The gene defective in WS (WRN) has been cloned and encodes a protein
      homologous to several helicases, including Escherichia coli RecQ, the human Bloom
      syndrome protein (BLM), and Saccharomyces cerevisiae Sgs1p. To better define the
      function of WRN protein we have determined its subcellular localization. Indirect
      immunofluorescence using polyclonal anti-human WRN shows a predominant nucleolar
      localization. Studies of WRN mutant cells lines confirmed the specificity of
      antibody recognition. No difference was seen in the subcellular localization of
      the WRN protein in a variety of normal and transformed human cell lines,
      including both carcinomas and sarcomas. The nucleolar localization of human WRN
      protein was supported by the finding that upon biochemical subcellular
      fractionation, WRN protein is present in an increased concentration in a
      subnuclear fraction enriched for nucleolar proteins. We have also determined the
      subcellular localization of the mouse WRN homologue (mWRN). In contrast to human
      WRN protein, mWRN protein is present diffusely throughout the nucleus.
      Understanding the function of WRN in these organisms of vastly differing lifespan
      may yield new insights into the mechanisms of lifespan determination.

PMID- 9618509
TI  - A genetic record of population isolation in pocket gophers during Holocene
      climatic change.
AB  - A long-standing question in Quaternary paleontology is whether climate-induced,
      population-level phenotypic change is a result of large-scale migration or
      evolution in isolation. To directly measure genetic variation through time,
      ancient DNA and morphologic variation was measured over 2,400 years in a Holocene
      sequence of pocket gophers (Thomomys talpoides) from Lamar Cave, Yellowstone
      National Park, Wyoming. Ancient specimens and modern samples collected near Lamar
      Cave share mitochondrial cytochrome b sequences that are absent from adjacent
      localities, suggesting that the population was isolated for the entire period. In
      contrast, diastemal length, a morphologic character correlated with body size and
      nutritional level, changed predictably in response to climatic change. Our
      results demonstrate that small mammal populations can experience the long-term
      isolation assumed by many theoretical models of microevolutionary change.

PMID- 9618511
TI  - soc-2 encodes a leucine-rich repeat protein implicated in fibroblast growth
      factor receptor signaling.
AB  - Activation of fibroblast growth factor (FGF) receptors elicits diverse cellular
      responses including growth, mitogenesis, migration, and differentiation. The
      intracellular signaling pathways that mediate these important processes are not
      well understood. In Caenorhabditis elegans, suppressors of clr-1 identify genes,
      termed soc genes, that potentially mediate or activate signaling through the EGL
      15 FGF receptor. We demonstrate that three soc genes, soc-1, soc-2, and sem-5,
      suppress the activity of an activated form of the EGL-15 FGF receptor, consistent
      with the soc genes functioning downstream of EGL-15. We show that soc-2 encodes a
      protein composed almost entirely of leucine-rich repeats, a domain implicated in
      protein-protein interactions. We identified a putative human homolog, SHOC-2,
      which is 54% identical to SOC-2. We find that shoc-2 maps to 10q25, shoc-2 mRNA
      is expressed in all tissues assayed, and SHOC-2 protein is cytoplasmically
      localized. Within the leucine-rich repeats of both SOC-2 and SHOC-2 are two YXNX
      motifs that are potential tyrosine-phosphorylated docking sites for the SEM
      5/GRB2 Src homology 2 domain. However, phosphorylation of these residues is not
      required for SOC-2 function in vivo, and SHOC-2 is not observed to be tyrosine
      phosphorylated in response to FGF stimulation. We conclude that this genetic
      system has allowed for the identification of a conserved gene implicated in
      mediating FGF receptor signaling in C. elegans.

PMID- 9618510
TI  - SIRE-1, a copia/Ty1-like retroelement from soybean, encodes a retroviral envelope
      like protein.
AB  - The soybean genome hosts a family of several hundred, relatively homogeneous
      copies of a large, copia/Ty1-like retroelement designated SIRE-1. A copy of this
      element has been recovered from a Glycine max genomic library. DNA sequence
      analysis of two SIRE-1 subclones revealed that SIRE-1 contains a long,
      uninterrupted, ORF between the 3' end of the pol ORF and the 3' long terminal
      repeat (LTR), a region that harbors the env gene in retroviral genomes.
      Conceptual translation of this second ORF produces a 70-kDa protein. Computer
      analyses of the amino acid sequence predicted patterns of transmembrane domains,
      alpha-helices, and coiled coils strikingly similar to those found in mammalian
      retroviral envelope proteins. In addition, a 65-residue, proline-rich domain is
      characterized by a strong amino acid compositional bias virtually identical to
      that of the 60-amino acid, proline-rich neutralization domain of the feline
      leukemia virus surface protein. The assignment of SIRE-1 to the copia/Ty1 family
      was confirmed by comparison of the conceptual translation of its reverse
      transcriptase-like domain with those of other retroelements. This finding
      suggests the presence of a proretrovirus in a plant genome and is the strongest
      evidence to date for the existence of a retrovirus-like genome closely related to
      copia/Ty1 retrotransposons.

PMID- 9618512
TI  - Heteroduplex joint formation in Escherichia coli recombination is initiated by
      pairing of a 3'-ending strand.
AB  - The formation of heteroduplex joints in Escherichia coli recombination is
      initiated by invasion of double-stranded DNA by a single-stranded homologue. To
      determine the polarity of the invasive strand, linear molecules with direct
      terminal repeats were released by in vivo restriction of infecting chimeric phage
      DNA and heteroduplex products of intramolecular recombination were analyzed. With
      this substrate, the invasive strand is expected to be incorporated into the
      circular crossover product and the complementary strand is expected to be
      incorporated into the reciprocal linear product. Strands of both polarities were
      incorporated into heteroduplex structures, but only strands ending 3' at the
      break were incorporated into circular products. This result indicates that
      invasion of the 3'-ending strand initiates the heteroduplex joint formation and
      that the complementary 5'-ending strand is incorporated into heteroduplex
      structures in the process of reciprocal strand exchange. The polarity of the
      invasive strand was not affected by recD, recJ, or xonA mutations. However, xonA
      and recJ mutations increased the proportion of heteroduplexes containing 5'
      ending strands. This observation suggests that RecJ exonuclease and exonuclease I
      may enhance recombination by degrading the displaced strands during branch
      migration and thereby causing strand exchange to be unidirectional.

PMID- 9618513
TI  - A yeast model for the study of Batten disease.
AB  - Although the CLN3 gene for Batten disease, the most common inherited
      neurovisceral storage disease of childhood, was identified in 1995, the function
      of the corresponding protein still remains elusive. We previously cloned the
      Saccharomyces cerevisiae homologue to the human CLN3 gene, designated BTN1, which
      is not essential and whose product is 39% identical and 59% similar to Cln3p. We
      report that btn1-Delta deletion yeast strains are more resistant to D-(-)-threo-2
      amino-1-[p-nitrophenyl]-1,3-propanediol (denoted ANP), a phenotype that is
      complemented in yeast by the human CLN3 gene. Furthermore, the severity of Batten
      disease in humans and the degree of ANP resistance in yeast are related when the
      equivalent amino acid replacements in Cln3p and Btn1p are compared. These results
      indicate that yeast can be used as a model for the study of Batten disease.

PMID- 9618514
TI  - Identification of multiple cancer/testis antigens by allogeneic antibody
      screening of a melanoma cell line library.
AB  - Cancer/testis (CT) antigens-immunogenic protein antigens that are expressed in
      testis and a proportion of diverse human cancer types-are promising targets for
      cancer vaccines. To identify new CT antigens, we constructed an expression cDNA
      library from a melanoma cell line that expresses a wide range of CT antigens and
      screened the library with an allogeneic melanoma patient serum known to contain
      antibodies against two CT antigens, MAGE-1 and NY-ESO-1. cDNA clones isolated
      from this library identified four CT antigen genes: MAGE-4a, NY-ESO-1, LAGE-1,
      and CT7. Of these four, only MAGE-4a and NY-ESO-1 proteins had been shown to be
      immunogenic. LAGE-1 is a member of the NY-ESO-1 gene family, and CT7 is a newly
      defined gene with partial sequence homology to the MAGE family at its carboxyl
      terminus. The predicted CT7 protein, however, contains a distinct repetitive
      sequence at the 5' end and is much larger than MAGE proteins. Our findings
      document the immunogenicity of LAGE-1 and CT7 and emphasize the power of
      serological analysis of cDNA expression libraries in identifying new human tumor
      antigens.

PMID- 9618515
TI  - A physiologic function for p-glycoprotein (MDR-1) during the migration of
      dendritic cells from skin via afferent lymphatic vessels.
AB  - P-glycoprotein (MDR-1) is a well-known transporter that mediates efflux of
      chemotherapeutic agents from the intracellular milieu and thereby contributes to
      drug resistance. MDR-1 also is expressed by nonmalignant cells, including
      leukocytes, but physiologic functions for MDR-1 are poorly defined. Using an
      initial screening assay that included >100 mAbs, we observed that neutralizing
      mAbs MRK16, UIC2, and 4E3 against MDR-1 specifically and potently blocked basal
      to-apical transendothelial migration of mononuclear phagocytes, a process that
      may mimic their migration into lymphatic vessels. Antagonists of MDR-1 then were
      used in a model of authentic lymphatic clearance. In this model, antigen
      presenting dendritic cells (DC) migrate out of explants of cultured human skin
      and into the culture medium via dermal lymphatic vessels. DC and T cells derived
      from skin expressed MDR-1 on their surfaces. Addition of anti-MDR-1 mAbs MRK16,
      UIC2, or the MDR-1 antagonist verapamil to skin explants at the onset of culture
      inhibited the appearance of DC, and accompanying T cells, in the culture medium
      by approximately 70%. Isotype-matched control mAbs against other DC molecules
      including CD18, CD31, and major histocompatibility complex I did not block. In
      the presence of MDR-1 antagonists, epidermal DC were retained in the epidermis,
      in contrast to control conditions. In summary, this work identifies a physiologic
      function for MDR-1 during the mobilization of DC and begins to elucidate how
      these critical antigen-presenting cells migrate from the periphery to lymph nodes
      to initiate T lymphocyte-mediated immunity.

PMID- 9618516
TI  - T1/ST2 is preferentially expressed on murine Th2 cells, independent of
      interleukin 4, interleukin 5, and interleukin 10, and important for Th2 effector
      function.
AB  - T helper (Th) cells can be categorized according to their cytokine expression.
      The differential induction of Th cells expressing Th1 and/or Th2 cytokines is key
      to the regulation of both protective and pathological immune responses. Cytokines
      are expressed transiently and there is a lack of stably expressed surface
      molecules, significant for functionally different types of Th cells. Such
      molecules are of utmost importance for the analysis and selective functional
      modulation of Th subsets and will provide new therapeutic strategies for the
      treatment of allergic or autoimmune diseases. To this end, we have identified
      potential target genes preferentially expressed in Th2 cells, expressing
      interleukin (IL)-4, IL-5, and/or IL-10, but not interferon-gamma. One such gene,
      T1/ST2, is expressed stably on both Th2 clones and Th2-polarized cells activated
      in vivo or in vitro. T1/ST2 expression is independent of induction by IL-4, IL-5,
      or IL-10. T1/ST2 plays a critical role in Th2 effector function. Administration
      of either a mAb against T1/ST2 or recombinant T1/ST2 fusion protein attenuates
      eosinophilic inflammation of the airways and suppresses IL-4 and IL-5 production
      in vivo following adoptive transfer of Th2 cells.

PMID- 9618517
TI  - Differential expression of major histocompatibility complex class II genes on
      murine macrophages associated with T cell cytokine profile and
      protective/suppressive effects.
AB  - Protective/suppressive major histocompatibility complex (MHC) class II alleles
      have been identified in humans and mice where they exert a disease-protective and
      immunosuppressive effect. Various modes of action have been proposed, among them
      differential expression of MHC class II genes in different types of antigen
      presenting cells impacting on the T helper type 1 (Th1)-Th2 balance. To test this
      possibility, the expression of H-2 molecules from the four haplotypes H-2(b), H
      2(d), H-2(k), and H-2(q) was determined on bone marrow-derived macrophages
      (BMDMs) and splenic B cells. The I-Ab and I-Ek molecules, both well characterized
      as protective/suppressive, are expressed at a high level on almost all CD11b+
      BMDMs for 5-8 days, after which expression slowly declines. In contrast, I-Ad, I
      Ak, and I-Aq expression is lower, peaks over a shorter period, and declines more
      rapidly. No differential expression could be detected on B cells. In addition,
      the differential MHC class II expression found on macrophages skews the cytokine
      response of T cells as shown by an in vitro restimulation assay with BMDMs as
      antigen-presenting cells. The results indicate that macrophages of the
      protective/suppressive haplotypes express MHC class II molecules at a high level
      and exert Th1 bias, whereas low-level expression favors a Th2 response. We
      suggest that the extent of expression of the class II gene gates the back signal
      from T cells and in this way controls the activity of macrophages. This effect
      mediated by polymorphic nonexon segments of MHC class II genes may play a role in
      determining disease susceptibility in humans and mice.

PMID- 9618518
TI  - Crystal structure of chemically synthesized [N33A] stromal cell-derived factor
      1alpha, a potent ligand for the HIV-1 "fusin" coreceptor.
AB  - Stromal cell-derived factor-1alpha (SDF-1alpha ) is a member of the chemokine
      superfamily and functions as a growth factor and chemoattractant through
      activation of CXCR4/LESTR/Fusin, a G protein-coupled receptor. This receptor also
      functions as a coreceptor for T-tropic syncytium-inducing strains of HIV-1. SDF
      1alpha antagonizes infectivity of these strains by competing with gp120 for
      binding to the receptor. The crystal structure of a variant SDF-1alpha ([N33A]SDF
      1alpha ) prepared by total chemical synthesis has been refined to 2.2-A
      resolution. Although SDF-1alpha adopts a typical chemokine beta-beta-beta-alpha
      topology, the packing of the alpha-helix against the beta-sheet is strikingly
      different. Comparison of SDF-1alpha with other chemokine structures confirms the
      hypothesis that SDF-1alpha may be either an ancestral protein from which all
      other chemokines evolved or the chemokine that is the least divergent from a
      primordial chemokine. The structure of SDF-1alpha reveals a positively charged
      surface ideal for binding to the negatively charged extracellular loops of the
      CXCR4 HIV-1 coreceptor. This ionic complementarity is likely to promote the
      interaction of the mobile N-terminal segment of SDF-1alpha with interhelical
      sites of the receptor, resulting in a biological response.

PMID- 9618519
TI  - A strategy for organ allografts without using immunosuppressants or irradiation.
AB  - A strategy to achieve regular and long lasting organ and tissue allografts
      without using immunosuppressants and/or irradiation has been established for
      mice. One hundred percent of skin allografts can be induced to survive >350 days
      after transplantation if spleen cells from the same donors are first injected
      into the portal vein of the recipients. The mechanisms underlying this long-term
      tolerance induction can be described as follows: (i) donor T cells from the
      spleen of the donor facilitate the acceptance of the allogeneic engraftment, (ii)
      donor-specific anergy is induced in the cytotoxic T-lymphocytes of the
      recipients, (iii) T helper type 2 cells become the dominant T cells in the
      recipients that are accepting the skin transplants, and (iv) a lasting chimerism
      (microchimerism) is established in these recipients. This strategy, perhaps with
      minor modifications, might permit one also to overcome major barriers to organ
      allografting in humans. If this were the case, it could represent production of
      long lasting immunologic tolerance without need for irradiation or cytotoxic
      chemo-preparative regimen and as such could greatly facilitate
      allotransplantation free of episodes of chronic or acute rejection or toxic and
      damaging preparatory regimens.

PMID- 9618520
TI  - Altered spectra of hypermutation in antibodies from mice deficient for the DNA
      mismatch repair protein PMS2.
AB  - Mutations are introduced into rearranged Ig variable genes at a frequency of 10(
      2) mutations per base pair by an unknown mechanism. Assuming that DNA repair
      pathways generate or remove mutations, the frequency and pattern of mutation will
      be different in variable genes from mice defective in repair. Therefore,
      hypermutation was studied in mice deficient for either the DNA nucleotide
      excision repair gene Xpa or the mismatch repair gene Pms2. High levels of
      mutation were found in variable genes from XPA-deficient and PMS2-deficient mice,
      indicating that neither nucleotide excision repair nor mismatch repair pathways
      generate hypermutation. However, variable genes from PMS2-deficient mice had
      significantly more adjacent base substitutions than genes from wild-type or XPA
      deficient mice. By using a biochemical assay, we confirmed that tandem mispairs
      were repaired by wild-type cells but not by Pms2(-/-) human or murine cells. The
      data indicate that tandem substitutions are produced by the hypermutation
      mechanism and then processed by a PMS2-dependent pathway.

PMID- 9618521
TI  - Interleukin-2 induces beta2-integrin-dependent signal transduction involving the
      focal adhesion kinase-related protein B (fakB).
AB  - beta2 integrin molecules are involved in a multitude of cellular events,
      including adhesion, migration, and cellular activation. Here, we studied the
      influence of beta2 integrins on interleukin-2 (IL-2)-mediated signal transduction
      in human CD4(+) T cell lines obtained from healthy donors and a leukocyte
      adhesion deficiency (LAD) patient. We show that IL-2 induces tyrosine
      phosphorylation of a 125-kDa protein and homotypic adhesion in beta2 integrin
      (CD18)-positive but not in beta2-integrin-negative T cells. EDTA, an inhibitor of
      integrin adhesion, blocks IL-2-induced tyrosine phosphorylation of the 125-kDa
      protein but not other proteins in beta2-integrin-positive T cells. Likewise, a
      beta2 integrin (CD18) antibody selectively inhibits induction of the 125-kDa
      phosphotyrosine protein, whereas cytokine-mediated tyrosine phosphorylation of
      other proteins is largely unaffected. Immunoprecipitation experiments indicate
      that the IL-2-induced 125-kDa phosphotyrosine protein is the focal adhesion
      kinase-related protein B (fakB). Thus, IL-2 induces strong tyrosine
      phosphorylation of fakB in beta2-integrin-positive but not in beta2-integrin
      negative T cells, and CD18 mAb selectively blocks IL-2-induced fakB-tyrosine
      phosphorylation in beta2-integrin-positive T cells. In parallel experiments, IL-2
      does not induce or augment tyrosine phosphorylation of p125(FAK). In conclusion,
      our data indicate that IL-2 induces beta2-integrin-dependent signal transduction
      events involving the tyrosine kinase substrate fakB.

PMID- 9618522
TI  - Characterization of mice deficient in aromatase (ArKO) because of targeted
      disruption of the cyp19 gene.
AB  - The formation of estrogens from C19 steroids is catalyzed by aromatase cytochrome
      P450 (P450arom), the product of the cyp19 gene. The actions of estrogen include
      dimorphic anatomical, functional, and behavioral effects on the development of
      both males and females, considerations that prompted us to examine the
      consequences of deficiency of aromatase activity in mice. Mice lacking a
      functional aromatase enzyme (ArKO) were generated by targeted disruption of the
      cyp19 gene. Male and female ArKO mice were born with the expected Mendelian
      frequency from F1 parents and grew to adulthood. Female ArKO mice at 9 weeks of
      age displayed underdeveloped external genitalia and uteri. Ovaries contained
      numerous follicles with abundant granulosa cells and evidence of antrum formation
      that appeared arrested before ovulation. No corpora lutea were present.
      Additionally the stroma were hyperplastic with structures that appeared to be
      atretic follicles. Development of the mammary glands approximated that of a
      prepubertal female. Examination of male ArKO mice of the same age revealed
      essentially normal internal anatomy but with enlargement of the male accessory
      sex glands because of increased content of secreted material. The testes appeared
      normal. Male ArKO mice are capable of breeding and produce litters of
      approximately average size. Whereas serum estradiol levels were at the limit of
      detection, testosterone levels were elevated, as were the levels of follicle
      stimulating hormone and luteinizing hormone. The phenotype of these animals
      differs markedly from that of the previously reported ERKO mice, in which the
      estrogen receptor alpha is deleted by targeted disruption.

PMID- 9618523
TI  - NF-kappaB activation and interleukin 6 production in fibroblasts by estrogen
      receptor-negative breast cancer cell-derived interleukin 1alpha.
AB  - Several angiogenic factors and extracellular matrix-degrading enzymes that
      promote invasion and metastasis of cancer are produced by stromal fibroblasts
      that surround cancer cells. The expression of genes that code for some of these
      proteins is regulated by the transcription factor NF-kappaB. In this report, we
      demonstrate that conditioned medium (CM) from estrogen receptor (ER)-negative but
      not ER-positive breast cancer cells induces NF-kappaB in fibroblasts. In
      contrast, CM from both ER-positive and ER-negative breast cancer cells induces NF
      kappaB in macrophages and endothelial cells. NF-kappaB activation in fibroblasts
      was accompanied by induction of interleukin 6 (IL-6) and urokinase plasminogen
      activator (uPA), both of which promote angiogenesis and metastasis. A survey of
      cytokines known for their ability to induce NF-kappaB identified IL-1alpha as the
      factor responsible for NF-kappaB activation in fibroblasts. Analysis of primary
      breast carcinomas revealed the presence of IL-1alpha transcripts in majority of
      lymph node-positive breast cancers. These results along with the known role of IL
      1alpha and IL-6 in osteoclast formation provide insight into the mechanism of
      metastasis and hypercalcemia in advanced breast cancers.

PMID- 9618524
TI  - Photodynamic therapy results in induction of WAF1/CIP1/P21 leading to cell cycle
      arrest and apoptosis.
AB  - Photodynamic therapy (PDT) is a promising new modality that utilizes a
      combination of a photosensitizing chemical and visible light for the management
      of a variety of solid malignancies. The mechanism of PDT-mediated cell killing is
      not well defined. We investigated the involvement of cell cycle regulatory events
      during silicon phthalocyanine (Pc4)-PDT-mediated apoptosis in human epidermoid
      carcinoma cells A431. PDT resulted in apoptosis, inhibition of cell growth, and
      G0-G1 phase arrest of the cell cycle, in a time-dependent fashion. Western blot
      analysis revealed that PDT results in an induction of the cyclin kinase inhibitor
      WAF1/CIP1/p21, and a down-regulation of cyclin D1 and cyclin E, and their
      catalytic subunits cyclin-dependent kinase (cdk) 2 and cdk6. The treatment also
      resulted in a decrease in kinase activities associated with all the cdks and
      cyclins examined. PDT also resulted in (i) an increase in the binding of cyclin
      D1 and cdk6 toward WAF1/CIP1/p21, and (ii) a decrease in the binding of cyclin D1
      toward cdk2 and cdk6. The binding of cyclin E and cdk2 toward WAF1/CIP1/p21, and
      of cyclin E toward cdk2 did not change by the treatment. These data suggest that
      PDT-mediated induction of WAF1/CIP1/p21 results in an imposition of artificial
      checkpoint at G1 --> S transition thereby resulting in an arrest of cells in G0
      G1 phase of the cell cycle through inhibition in the cdk2, cdk6, cyclin D1, and
      cyclin E. We suggest that this arrest is an irreversible process and the cells,
      unable to repair the damages, ultimately undergo apoptosis.

PMID- 9618525
TI  - Overexpression of transforming growth factor beta1 in arterial endothelium causes
      hyperplasia, apoptosis, and cartilaginous metaplasia.
AB  - Uninjured rat arteries transduced with an adenoviral vector expressing an active
      form of transforming growth factor beta1 (TGF-beta1) developed a cellular and
      matrix-rich neointima, with cartilaginous metaplasia of the vascular media.
      Explant cultures of transduced arteries showed that secretion of active TGF-beta1
      ceased by 4 weeks, the time of maximal intimal thickening. Between 4 and 8 weeks,
      the cartilaginous metaplasia resolved and the intimal lesions regressed almost
      completely, in large part because of massive apoptosis. Thus, locally expressed
      TGF-beta1 promotes intimal growth and appears to cause transdifferentiation of
      vascular smooth muscle cells into chondrocytes. Moreover, TGF-beta1 withdrawal is
      associated with regression of vascular lesions. These data suggest an unexpected
      plasticity of the adult vascular smooth muscle cell phenotype and provide an
      etiology for cartilaginous metaplasia of the arterial wall. Our observations may
      help to reconcile divergent views of the role of TGF-beta1 in vascular disease.

PMID- 9618526
TI  - The "Spot 14" gene resides on the telomeric end of the 11q13 amplicon and is
      expressed in lipogenic breast cancers: implications for control of tumor
      metabolism.
AB  - Enhanced long chain fatty acid synthesis may occur in breast cancer, where it is
      necessary for tumor growth and predicts a poor prognosis. "Spot 14" (S14) is a
      carbohydrate- and thyroid hormone-inducible nuclear protein specific to liver,
      adipose, and lactating mammary tissues that functions to activate genes encoding
      the enzymes of fatty acid synthesis. Amplification of chromosome region 11q13,
      where the S14 gene (THRSP) resides, also predicts a poor prognosis in breast
      tumors. We localized the S14 gene between markers D11S906 and D11S937, at the
      telomeric end of the amplified region at 11q13, and found that it was amplified
      and expressed in breast cancer-derived cell lines. Moreover, concordant
      expression of S14 and a key lipogenic enzyme (acetyl-CoA carboxylase) in a panel
      of primary breast cancer specimens strongly supported a role for S14 as a
      determinant of tumor lipid metabolism. S14 expression provides a
      pathophysiological link between two prognostic indicators in breast cancer:
      enhanced lipogenesis and 11q13 amplification.

PMID- 9618527
TI  - A physiological role of the adenosine A3 receptor: sustained cardioprotection.
AB  - Adenosine released during cardiac ischemia exerts a potent, protective effect in
      the heart. A newly recognized adenosine receptor, the A3 subtype, is expressed on
      the cardiac ventricular cell, and its activation protects the ventricular heart
      cell against injury during a subsequent exposure to ischemia. A cultured chicken
      ventricular myocyte model was used to investigate the cardioprotective role of a
      novel adenosine A3 receptor. The protection mediated by prior activation of A3
      receptors exhibits a significantly longer duration than that produced by
      activation of the adenosine A1 receptor. Prior exposure of the myocytes to brief
      ischemia also protected them against injury sustained during a subsequent
      exposure to prolonged ischemia. The adenosine A3 receptor-selective antagonist 3
      ethyl 5-benzyl-2-methyl-6-phenyl-4-phenylethynyl-1, 4-(+/-)-dihydropyridine-3,5
      dicarboxylate (MRS1191) caused a biphasic inhibition of the protective effect of
      the brief ischemia. The concomitant presence of the A1 receptor antagonist 8
      cyclopentyl-1,3-dipropylxanthine (DPCPX) converted the MRS1191-induced dose
      inhibition curve to a monophasic one. The combined presence of both antagonists
      abolished the protective effect induced by the brief ischemia. Thus, activation
      of both A1 and A3 receptors is required to mediate the cardioprotective effect of
      the brief ischemia. Cardiac atrial cells lack native A3 receptors and exhibit a
      shorter duration of cardioprotection than do ventricular cells. Transfection of
      atrial cells with cDNA encoding the human adenosine A3 receptor causes a
      sustained A3 agonist-mediated cardioprotection. The study indicates that cardiac
      adenosine A3 receptor mediates a sustained cardioprotective function and
      represents a new cardiac therapeutic target.

PMID- 9618528
TI  - Expression of a beta-adrenergic receptor kinase 1 inhibitor prevents the
      development of myocardial failure in gene-targeted mice.
AB  - Heart failure is accompanied by severely impaired beta-adrenergic receptor
      (betaAR) function, which includes loss of betaAR density and functional
      uncoupling of remaining receptors. An important mechanism for the rapid
      desensitization of betaAR function is agonist-stimulated receptor phosphorylation
      by the betaAR kinase (betaARK1), an enzyme known to be elevated in failing human
      heart tissue. To investigate whether alterations in betaAR function contribute to
      the development of myocardial failure, transgenic mice with cardiac-restricted
      overexpression of either a peptide inhibitor of betaARK1 or the beta2AR were
      mated into a genetic model of murine heart failure (MLP-/-). In vivo cardiac
      function was assessed by echocardiography and cardiac catheterization. Both MLP-/
      and MLP-/-/beta2AR mice had enlarged left ventricular (LV) chambers with
      significantly reduced fractional shortening and mean velocity of circumferential
      fiber shortening. In contrast, MLP-/-/betaARKct mice had normal LV chamber size
      and function. Basal LV contractility in the MLP-/-/betaARKct mice, as measured by
      LV dP/dtmax, was increased significantly compared with the MLP-/- mice but less
      than controls. Importantly, heightened betaAR desensitization in the MLP-/- mice,
      measured in vivo (responsiveness to isoproterenol) and in vitro (isoproterenol
      stimulated membrane adenylyl cyclase activity), was completely reversed with
      overexpression of the betaARK1 inhibitor. We report here the striking finding
      that overexpression of this inhibitor prevents the development of cardiomyopathy
      in this murine model of heart failure. These findings implicate abnormal betaAR-G
      protein coupling in the pathogenesis of the failing heart and point the way
      toward development of agents to inhibit betaARK1 as a novel mode of therapy.

PMID- 9618529
TI  - Absence of cytokine receptor-dependent specificity in red blood cell
      differentiation in vivo.
AB  - Erythropoietin (EPO) is required for red blood cell development, but whether EPO
      specific signals directly instruct erythroid differentiation is unknown. We used
      a dominant system in which constitutively active variants of the EPO receptor
      were introduced into erythroid progenitors in mice. Chimeric receptors were
      constructed by replacing the cytoplasmic tail of constitutively active variants
      of the EPO receptor with tails of diverse cytokine receptors. Receptors linked to
      granulocyte or platelet production supported complete erythroid development in
      vitro and in vivo, as did the growth hormone receptor, a nonhematopoietic
      receptor. Therefore, EPOR-specific signals are not required for terminal
      differentiation of erythrocytes. Furthermore, we found that cellular context can
      influence cytokine receptor signaling.

PMID- 9618530
TI  - Contributions of cell kill and posttreatment tumor growth rates to the
      repopulation of intracerebral 9L tumors after chemotherapy: an MRI study.
AB  - The drought of progress in clinical brain tumor therapy provides an impetus for
      developing new treatments as well as methods for testing therapeutics in animal
      models. The inability of traditional assays to simultaneously measure tumor size,
      location, growth kinetics, and cell kill achieved by a treatment complicates the
      interpretation of therapy experiments in animal models. To address these issues,
      tumor volume measurements obtained from serial magnetic resonance images were
      used to noninvasively estimate cell kill values in individual rats with
      intracerebral 9L tumors after treatment with 0.5, 1, or 2 x LD10 doses of 1,3
      bis(2-chloroethyl)-1-nitrosourea. The calculated cell kill values were
      consistently lower than those reported using traditional assays. A dose-dependent
      increase in 9L tumor doubling time after treatment was observed that
      significantly contributed to the time required for surviving cells to repopulate
      the tumor mass. This study reveals that increases in animal survival are not
      exclusively attributable to the fraction of tumor cells killed but rather are a
      function of the cell kill and repopulation kinetics, both of which vary with
      treatment dose.

PMID- 9618531
TI  - Collagen-binding growth factors: production and characterization of functional
      fusion proteins having a collagen-binding domain.
AB  - The autocrine/paracrine peptide signaling molecules such as growth factors have
      many promising biologic activities for clinical applications. However, one cannot
      expect specific therapeutic effects of the factors administered by ordinary drug
      delivery systems as they have limited target specificity and short half-lives in
      vivo. To overcome the difficulties in using growth factors as therapeutic agents,
      we have produced fusion proteins consisting of growth factor moieties and a
      collagen-binding domain (CBD) derived from Clostridium histolyticum collagenase.
      The fusion proteins carrying the epidermal growth factor (EGF) or basic
      fibroblast growth factor (bFGF) at the N terminal of CBD (CBEGF/CBFGF) tightly
      bound to insoluble collagen and stimulated the growth of BALB/c 3T3 fibroblasts
      as much as the unfused counterparts. CBEGF, when injected subcutaneously into
      nude mice, remained at the sites of injection for up to 10 days, whereas EGF was
      not detectable 24 h after injection. Although CBEGF did not exert a growth
      promoting effect in vivo, CBFGF, but not bFGF, strongly stimulated the DNA
      synthesis in stromal cells at 5 days and 7 days after injection. These results
      indicate that CBD may be used as an anchoring unit to produce fusion proteins
      nondiffusible and long-lasting in vivo.

PMID- 9618532
TI  - The drug efflux protein, P-glycoprotein, additionally protects drug-resistant
      tumor cells from multiple forms of caspase-dependent apoptosis.
AB  - Multidrug resistance mediated by the drug efflux protein, P-glycoprotein (P-gp),
      is one mechanism that tumor cells use to escape death induced by chemotherapeutic
      agents. However, the mechanism by which P-gp confers resistance to a large
      variety of structurally diverse molecules has remained elusive. In this study,
      classical multidrug resistant human CEM and K562 tumor cell lines expressing high
      levels of P-gp were less sensitive to multiple forms of caspase-dependent cell
      death, including that mediated by cytotoxic drugs and ligation of Fas. The DNA
      fragmentation and membrane damage inflicted by these stimuli were defined as
      caspase dependent by various soluble peptide fluoromethylketone caspase
      inhibitors. Inhibition of P-gp function by the anti-P-gp mAb MRK-16 or verapamil
      could reverse resistance to these forms of cell death. Inhibition of P-gp
      function also enhanced drug or Fas-mediated activation of caspase-3 in drug
      resistant CEM cells. By contrast, caspase-independent cell death events in the
      same cells, including those mediated by pore-forming proteins or intact NK cells,
      were not affected by P-gp expression. These observations suggest that, in
      addition to effluxing drugs, P-gp may play a specific role in regulating some
      caspase-dependent apoptotic pathways.

PMID- 9618533
TI  - Ammonia acquisition in enteric bacteria: physiological role of the
      ammonium/methylammonium transport B (AmtB) protein.
AB  - Homologues of the amtB gene of enteric bacteria exist in all three domains of
      life. Although their products are required for transport of the ammonium analogue
      methylammonium in washed cells, only in Saccharomyces cerevisiae have they been
      shown to be necessary for growth at low NH4+ concentrations. We now demonstrate
      that an amtB strain of Escherichia coli also grows slowly at low NH4+
      concentrations in batch culture, but only at pH values below 7. In addition, we
      find that the growth defect of an S. cerevisiae triple-mutant strain lacking the
      function of three homologues of the ammonium/methylammonium transport B (AmtB)
      protein [called methylammonium/ammonium permeases (MEP)] that was observed at pH
      6.1 is relieved at pH 7.1. These results provide direct evidence that AmtB
      participates in acquisition of NH4+/NH3 in bacteria as well as eucarya. Because
      NH3 is the species limiting at low pH for a given total concentration of NH4+ +
      NH3, results with both organisms indicate that AmtB/MEP proteins function in
      acquisition of the uncharged form. We confirmed that accumulation of
      [14C]methylammonium depends on its conversion to gamma-N-methylglutamine, an
      energy-requiring reaction catalyzed by glutamine synthetase, and found that at pH
      7, constitutive expression of AmtB did not relieve the growth defects of a mutant
      strain of Salmonella typhimurium that appears to require a high internal
      concentration of NH4+/NH3. Hence, contrary to previous views, we propose that
      AmtB/MEP proteins increase the rate of equilibration of the uncharged species,
      NH3, across the cytoplasmic membrane rather than actively transporting-that is,
      concentrating-the charged species, NH4+.

PMID- 9618534
TI  - CTXphi immunity: application in the development of cholera vaccines.
AB  - CTXphi is a filamentous bacteriophage that encodes cholera toxin, the principal
      virulence factor of Vibrio cholerae. CTXphi is unusual among filamentous phages
      because it encodes a repressor and forms lysogens. CTXphi can infect the existing
      live-attenuated V. cholerae vaccine strains derived from either the El Tor or
      classical V. cholerae biotypes and result in vaccine reversion to toxinogenicity.
      Intraintestinal CTXphi transduction assays were used to demonstrate that El Tor
      biotype strains of V. cholerae are immune to infection with the El Tor-derived
      CTXphi, whereas classical strains are not. The El Tor CTXphi repressor, RstR, was
      sufficient to render classical strains immune to infection with the El Tor
      CTXphi. The DNA sequences of the classical and El Tor CTXphi repressors and their
      presumed cognate operators are highly diverged, whereas the sequences that
      surround this "immunity" region are nearly identical. Transcriptional fusion
      studies revealed that the El Tor RstR mediated repression of an El Tor rstA-lacZ
      fusion but did not repress a classical rstA-lacZ fusion. Likewise, the classical
      RstR only repressed a classical rstA-lacZ fusion. Thus, similar to the
      mechanistic basis for heteroimmunity among lambdoid phages, the specificity of
      CTXphi immunity is based on the divergence of the sequences of repressors and
      their operators. Expression of the El Tor rstR in either El Tor or classical live
      attenuated V. cholerae vaccine strains effectively protected these vaccines from
      CTXphi infection. Introduction of rstR into V. cholerae vaccine strains should
      enhance their biosafety.

PMID- 9618536
TI  - Quorum sensing in Escherichia coli and Salmonella typhimurium.
AB  - Escherichia coli and Salmonella typhimurium strains grown in Luria-Bertani medium
      containing glucose secrete a small soluble heat labile organic molecule that is
      involved in intercellular communication. The factor is not produced when the
      strains are grown in Luria-Bertani medium in the absence of glucose. Maximal
      secretion of the substance occurs in midexponential phase, and the extracellular
      activity is degraded as the glucose is depleted from the medium or by the onset
      of stationary phase. Destruction of the signaling molecule in stationary phase
      indicates that, in contrast to other quorum-sensing systems, quorum sensing in E.
      coli and S. typhimurium is critical for regulating behavior in the prestationary
      phase of growth. Our results further suggest that the signaling factor produced
      by E. coli and S. typhimurium is used to communicate both the cell density and
      the metabolic potential of the environment. Several laboratory and clinical
      strains of E. coli and S. typhimurium were screened for production of the
      signaling molecule, and most strains make it under conditions similar to those
      shown here for E. coli AB1157 and S. typhimurium LT2. However, we also show that
      E. coli strain DH5alpha does not make the soluble factor, indicating that this
      highly domesticated strain has lost the gene(s) or biosynthetic machinery
      necessary to produce the signaling substance. Implications for the involvement of
      quorum sensing in pathogenesis are discussed.

PMID- 9618535
TI  - Agrobacterium VirD2 protein interacts with plant host cyclophilins.
AB  - Agrobacterium tumefaciens induces crown gall tumors on plants by transferring a
      nucleoprotein complex, the T-complex, from the bacterium to the plant cell. The T
      complex consists of T-DNA, a single-stranded DNA segment of the tumor-inducing
      plasmid, VirD2, an endonuclease covalently bound to the 5' end of the T-DNA, and
      perhaps VirE2, a single-stranded DNA binding protein. The yeast two-hybrid system
      was used to screen for proteins interacting with VirD2 and VirE2 to identify
      components in Arabidopsis thaliana that interact with the T-complex. Three VirD2-
      and two VirE2-interacting proteins were identified. Here we characterize the
      interactions of VirD2 with two isoforms of Arabidopsis cyclophilins identified by
      using this analysis. The VirD2 domain interacting with the cyclophilins is
      distinct from the endonuclease, omega, and the nuclear localization signal
      domains. The VirD2-cyclophilin interaction is disrupted in vitro by cyclosporin
      A, which also inhibits Agrobacterium-mediated transformation of Arabidopsis and
      tobacco. These data strongly suggest that host cyclophilins play a role in T-DNA
      transfer.

PMID- 9618537
TI  - A site-specific recombinase is required for competitive root colonization by
      Pseudomonas fluorescens WCS365.
AB  - A colonization mutant of the efficient root-colonizing biocontrol strain
      Pseudomonas fluorescens WCS365 is described that is impaired in competitive root
      tip colonization of gnotobiotically grown potato, radish, wheat, and tomato,
      indicating a broad host range mutation. The colonization of the mutant is also
      impaired when studied in potting soil, suggesting that the defective gene also
      plays a role under more natural conditions. A DNA fragment that is able to
      complement the mutation for colonization revealed a multicistronic transcription
      unit composed of at least six ORFs with similarity to lppL, lysA, dapF,
      orf235/233, xerC/sss, and the largely incomplete orf238. The transposon insertion
      in PCL1233 appeared to be present in the orf235/233 homologue, designated orf240.
      Introduction of a mutation in the xerC/sss homologue revealed that the xerC/sss
      gene homologue rather than orf240 is crucial for colonization. xerC in
      Escherichia coli and sss in Pseudomonas aeruginosa encode proteins that belong to
      the lambda integrase family of site-specific recombinases, which play a role in
      phase variation caused by DNA rearrangements. The function of the xerC/sss
      homologue in colonization is discussed in terms of genetic rearrangements
      involved in the generation of different phenotypes, thereby allowing a bacterial
      population to occupy various habitats. Mutant PCL1233 is assumed to be locked in
      a phenotype that is not well suited to compete for colonization in the
      rhizosphere. Thus we show the importance of phase variation in microbe-plant
      interactions.

PMID- 9618538
TI  - The Ti plasmid increases the efficiency of Agrobacterium tumefaciens as a
      recipient in virB-mediated conjugal transfer of an IncQ plasmid.
AB  - The T-DNA transfer apparatus of Agrobacterium tumefaciens mediates the delivery
      of the T-DNA into plant cells, the transfer of the IncQ plasmid RSF1010 into
      plant cells, and the conjugal transfer of RSF1010 between Agrobacteria. We show
      in this report that the Agrobacterium-to-Agrobacterium conjugal transfer
      efficiencies of RSF1010 increase dramatically if the recipient strain, as well as
      the donor strain, carries a wild-type Ti plasmid and is capable of vir gene
      expression. Investigation of possible mechanisms that could account for this
      increased efficiency revealed that the VirB proteins encoded by the Ti plasmid
      were required. Although, with the exception of VirB1, all of the proteins that
      form the putative T-DNA transfer apparatus (VirB1-11, VirD4) are required for an
      Agrobacterium strain to serve as an RSF1010 donor, expression of only a subset of
      these proteins is required for the increase in conjugal transfer mediated by the
      recipient. Specifically, VirB5, 6, 11, and VirD4 are essential donor components
      but are dispensable for the increased recipient capacity. Defined point mutations
      in virB9 affected donor and recipient capacities to the same relative extent,
      suggesting that similar functions of VirB9 are important in both of these
      contexts.

PMID- 9618539
TI  - Cell-specific viral targeting mediated by a soluble retroviral receptor-ligand
      fusion protein.
AB  - TVA, the cellular receptor for subgroup A avian leukosis viruses (ALV-A) can
      mediate viral entry when expressed as a transmembrane protein or as a
      glycosylphosphatidylinositol-linked protein on the surfaces of transfected
      mammalian cells. To determine whether mammalian cells can be rendered susceptible
      to ALV-A infection by attaching a soluble form of TVA to their plasma membranes,
      the TVA-epidermal growth factor (EGF) fusion protein was generated. TVA-EGF is
      comprised of the extracellular domain of TVA linked to the mature form of human
      EGF. Flow cytometric analysis confirmed that TVA-EGF is a bifunctional reagent
      capable of binding simultaneously to cell surface EGF receptors and to an ALV-A
      surface envelope-Ig fusion protein. TVA-EGF prebound to transfected mouse
      fibroblasts expressing either wild-type or kinase-deficient human EGF receptors,
      rendered these cells highly susceptible to infection by ALV-A vectors. Viral
      infection was blocked specifically in the presence of a recombinant human EGF
      protein, demonstrating that the binding of TVA-EGF to EGF receptors was essential
      for infectivity. These studies have demonstrated that a soluble TVA-ligand fusion
      protein can mediate viral infection when attached to specific cell surfaces,
      suggesting an approach for targeting retroviral infection to specific cell types.

PMID- 9618540
TI  - COS1, a two-component histidine kinase that is involved in hyphal development in
      the opportunistic pathogen Candida albicans.
AB  - Two-component histidine kinases recently have been found in eukaryotic organisms
      including fungi, slime molds, and plants. We describe the identification of a
      gene, COS1, from the opportunistic pathogen Candida albicans by using a PCR-based
      screening strategy. The sequence of COS1 indicates that it encodes a homolog of
      the histidine kinase Nik-1 from the filamentous fungus Neurospora crassa. COS1 is
      also identical to a gene called CaNIK1 identified in C. albicans by low
      stringency hybridization using CaSLN1 as a probe [Nagahashi, S., Mio, T., Yamada
      Okabe, T., Arisawa, M., Bussey, H. & Yamada-Okabe, H. (1998) Microbiol. 44, 425
      432]. We assess the function of COS1/CaNIK1 by constructing a diploid deletion
      mutant. Mutants lacking both copies of COS1 appear normal when grown as yeast
      cells; however, they exhibit defective hyphal formation when placed on solid agar
      media, either in response to nutrient deprivation or serum. In constrast to the
      Deltanik-1 mutant, the Deltacos1/Deltacos1 mutant does not demonstrate
      deleterious effects when grown in media of high osmolarity; however both Deltanik
      1 and Deltacos1/Deltacos1 mutants show defective hyphal formation. Thus, as
      predicted for Nik-1, Cos1p may be involved in some aspect of hyphal morphogenesis
      and may play a role in virulence properties of the organism.

PMID- 9618541
TI  - beta3 Integrins mediate the cellular entry of hantaviruses that cause respiratory
      failure.
AB  - Newly emerged hantaviruses replicate primarily in the pulmonary endothelium,
      cause acute platelet loss, and result in hantavirus pulmonary syndrome (HPS). We
      now report that specific integrins expressed on platelets and endothelial cells
      permit the cellular entry of HPS-associated hantaviruses. Infection with HPS
      associated hantaviruses, NY-1 and Sin Nombre virus (SNV), is inhibited by
      antibodies to beta3 integrins and by the beta3-integrin ligand, vitronectin. In
      contrast, infection with the nonpathogenic (no associated human disease) Prospect
      Hill virus was inhibited by fibronectin and beta1-specific antibodies but not by
      beta3-specific antibodies or vitronectin. Transfection with recombinant alphaIIb
      beta3 or alphav beta3 integrins rendered cells permissive to NY-1 and SNV but not
      Prospect Hill virus infection, indicating that alphaIIb beta3 and alphav beta3
      integrins mediate the entry of NY-1 and SNV hantaviruses. Furthermore, entry is
      divalent cation independent, not blocked by arginine-glycine-aspartic acid
      peptides and still mediated by, ligand-binding defective, alphaIIb beta3-integrin
      mutants. Hence, NY-1 and SNV entry is independent of beta3 integrin binding to
      physiologic ligands. These findings implicate integrins as cellular receptors for
      hantaviruses and indicate that hantavirus pathogenicity correlates with integrin
      usage.

PMID- 9618542
TI  - Aberrant intracellular localization of Varicella-Zoster virus regulatory proteins
      during latency.
AB  - Varicella-Zoster virus (VZV) is a herpesvirus that becomes latent in sensory
      neurons after primary infection (chickenpox) and subsequently may reactivate to
      cause zoster. The mechanism by which this virus maintains latency, and the
      factors involved, are poorly understood. Here we demonstrate, by
      immunohistochemical analysis of ganglia obtained at autopsy from seropositive
      patients without clinical symptoms of VZV infection that viral regulatory
      proteins are present in latently infected neurons. These proteins, which localize
      to the nucleus of cells during lytic infection, predominantly are detected in the
      cytoplasm of latently infected neurons. The restriction of regulatory proteins
      from the nucleus of latently infected neurons might interrupt the cascade of
      virus gene expression that leads to a productive infection. Our findings raise
      the possibility that VZV has developed a novel mechanism for maintenance of
      latency that contrasts with the transcriptional repression that is associated
      with latency of herpes simplex virus, the prototypic alpha herpesvirus.

PMID- 9618543
TI  - Patterns of brain angiogenesis after vascular endothelial growth factor
      administration in vitro and in vivo.
AB  - Vascular endothelial growth factor (VEGF) is a secreted endothelial cell mitogen
      that has been shown to induce vasculogenesis and angiogenesis in many organ
      systems and tumors. Considering the importance of VEGF to embryonic
      vascularization and survival, the effects of administered VEGF on developing or
      adult cerebrovasculature are unknown: can VEGF alter brain angiogenesis or mature
      cerebrovascular patterns? To examine these questions we exposed fetal, newborn,
      and adult rat cortical slice explants to graduated doses of recombinant VEGF. The
      effects of another known angiogenic factor, basic fibroblast growth factor
      (bFGF), were evaluated in a comparable manner. In addition, we infused VEGF via
      minipump into the adult cortex. Significant angiogenic effects were found in all
      VEGF experiments in a dose-responsive manner that were abolished by the addition
      of VEGF neutralizing antibody. Fetal and newborn explants had a highly complex
      network of branched vessels that immunoexpressed the flt-1 VEGF receptor, and flk
      1 VEGF receptor expression was determined by reverse transcription-PCR. Adult
      explants had enlarged, dilated vessels that appeared to be an expansion of the
      existing network. All bFGF-treated explants had substantially fewer vascular
      profiles. VEGF infusions produced both a remarkable localized neovascularization
      and, unexpectedly, the expression of flt-1 on reactive astrocytes but not on
      endothelial cells. The preponderance of neovascularization in vitro and in vivo,
      however, lacked the blood-brain barrier (BBB) phenotype marker, GLUT-1,
      suggesting that in brain the angiogenic role of VEGF may differ from a potential
      BBB functional role, i.e., transport and permeability. VEGF may serve an
      important capacity in neovascularization or BBB alterations after brain injury.

PMID- 9618544
TI  - Synchronization between prefrontal and posterior association cortex during human
      working memory.
AB  - We measured coherence between the electroencephalogram at different scalp sites
      while human subjects performed delayed response tasks. The tasks required the
      retention of either verbalizable strings of characters or abstract line drawings.
      In both types of tasks, a significant enhancement in coherence in the theta range
      (4-7 Hz) was found between prefrontal and posterior electrodes during 4-s
      retention intervals. During 6-s perception intervals, far fewer increases in
      theta coherence were found. Also in other frequency bands, coherence increased;
      however, the patterns of enhancement made a relevance for working memory
      processes seem unlikely. Our results suggest that working memory involves
      synchronization between prefrontal and posterior association cortex by phase
      locked, low frequency (4-7 Hz) brain activity.

PMID- 9618545
TI  - Activity differentially regulates the surface expression of synaptic AMPA and
      NMDA glutamate receptors.
AB  - Distinct subtypes of glutamate receptors often are colocalized at individual
      excitatory synapses in the mammalian brain yet appear to subserve distinct
      functions. To address whether neuronal activity may differentially regulate the
      surface expression at synapses of two specific subtypes of ionotropic glutamate
      receptors we epitope-tagged an AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionic acid) receptor subunit (GluR1) and an NMDA (N-methyl-D-aspartate)
      receptor subunit (NR1) on their extracellular termini and expressed these
      proteins in cultured hippocampal neurons using recombinant adenoviruses. Both
      receptor subtypes were appropriately targeted to the synaptic plasma membrane as
      defined by colocalization with the synaptic vesicle protein synaptophysin.
      Increasing activity in the network of cultured cells by prolonged blockade of
      inhibitory synapses with the gamma-aminobutyric acid type A receptor antagonist
      picrotoxin caused an activity-dependent and NMDA receptor-dependent decrease in
      surface expression of GluR1, but not NR1, at synapses. Consistent with this
      observation identical treatment of noninfected cultures decreased the
      contribution of endogenous AMPA receptors to synaptic currents relative to
      endogenous NMDA receptors. These results indicate that neuronal activity can
      differentially regulate the surface expression of AMPA and NMDA receptors at
      individual synapses.

PMID- 9618547
TI  - Additional evidence for an eight-transmembrane-domain topology for Caenorhabditis
      elegans and human presenilins.
AB  - Presenilins have been implicated in the genesis of Alzheimer's disease and in
      facilitating LIN-12/Notch activity during development. All presenilins have
      multiple hydrophobic regions that could theoretically span a membrane, and a
      description of the membrane topology is a crucial step toward deducing the
      mechanism of presenilin function. Previously, we proposed an eight-transmembrane
      domain model for presenilin, based on studies of the Caenorhabditis elegans SEL
      12 presenilin. Here, we describe experiments that support the view that two of
      the hydrophobic regions of SEL-12 function as the seventh and eighth
      transmembrane domains. Furthermore, we have shown that human presenilin 1 behaves
      like SEL-12 presenilin when analyzed by our methods. Our results provide
      additional experimental support for the eight-transmembrane-domain model of
      presenilin topology.

PMID- 9618546
TI  - Disease sequence from mutant rhodopsin allele to rod and cone photoreceptor
      degeneration in man.
AB  - Mutations in the gene encoding rhodopsin, the visual pigment in rod
      photoreceptors, lead to retinal degeneration in species from Drosophila to man.
      The pathogenic sequence from rod cell-specific mutation to degeneration of rods
      and cones remains unclear. To understand the disease process in man, we studied
      heterozygotes with 18 different rhodopsin gene mutations by using noninvasive
      tests of rod and cone function and retinal histopathology. Two classes of disease
      expression were found, and there was allele-specificity. Class A mutants lead to
      severely abnormal rod function across the retina early in life; topography of
      residual cone function parallels cone cell density. Class B mutants are
      compatible with normal rods in adult life in some retinal regions or throughout
      the retina, and there is a slow stereotypical disease sequence. Disease manifests
      as a loss of rod photoreceptor outer segments, not singly but in microscopic
      patches that coalesce into larger irregular areas of degeneration. Cone outer
      segment function remains normal until >75% of rod outer segments are lost. The
      topography of cone loss coincides with that of rod loss. Most class B mutants
      show an inferior-nasal to superior-temporal retinal gradient of disease
      vulnerability associated with visual cycle abnormalities. Class A mutant alleles
      behave as if cytotoxic; class B mutants can be relatively innocuous and
      epigenetic factors may play a major role in the retinal degeneration.

PMID- 9618548
TI  - Aurintricarboxylic acid prevents GLUR2 mRNA down-regulation and delayed
      neurodegeneration in hippocampal CA1 neurons of gerbil after global ischemia.
AB  - Aurintricarboxylic acid (ATA), an inhibitor of endonuclease activity and other
      protein-nucleic acid interactions, blocks apoptosis in several cell types and
      prevents delayed death of hippocampal pyramidal CA1 neurons induced by transient
      global ischemia. Global ischemia in rats and gerbils induces down-regulation of
      GluR2 mRNA and increased alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
      (AMPA)-induced Ca2+ influx in CA1 before neurodegeneration. This result and
      neuroprotection by antagonists of AMPA receptors suggests that formation of AMPA
      receptors lacking GluR2, and therefore Ca2+ permeable, leads to excessive Ca2+
      influx in response to endogenous glutamate; the resulting delayed neuronal death
      in CA1 exhibits many characteristics of apoptosis. In this study, we examined the
      effects of ATA on expression of mRNAs encoding glutamate receptor subunits in
      gerbil hippocampus after global ischemia. Administration of ATA by injection into
      the right cerebral ventricle 1 h before (but not 6 h after) bilateral carotid
      occlusion prevented the ischemia-induced decrease in GluR2 mRNA expression and
      the delayed neurodegeneration. These findings suggest that ATA is neuroprotective
      in ischemia by blocking the transcriptional changes leading to down-regulation of
      GluR2, rather than by simply blocking endonucleases, which presumably act later
      after Ca2+ influx initiates apoptosis. Maintaining formation of Ca2+ impermeable,
      GluR2 containing AMPA receptors could prevent delayed death of CA1 neurons after
      transient global ischemia, and block of GluR2 down-regulation may provide a
      further strategy for neuroprotection.

PMID- 9618549
TI  - On the actions that one nerve cell can have on another: distinguishing "drivers"
      from "modulators".
AB  - When one nerve cell acts on another, its postsynaptic effect can vary greatly. In
      sensory systems, inputs from "drivers" can be differentiated from those of
      "modulators." The driver can be identified as the transmitter of receptive field
      properties; the modulator can be identified as altering the probability of
      certain aspects of that transmission. Where receptive fields are not available,
      the distinction is more difficult and currently is undefined. We use the visual
      pathways, particularly the thalamic geniculate relay for which much relevant
      evidence is available, to explore ways in which drivers can be distinguished from
      modulators. The extent to which the distinction may apply first to other parts of
      the thalamus and then, possibly, to other parts of the brain is considered. We
      suggest the following distinctions: Cross-correlograms from driver inputs have
      sharper peaks than those from modulators; there are likely to be few drivers but
      many modulators for any one cell; and drivers are likely to act only through
      ionotropic receptors having a fast postsynaptic effect whereas modulators also
      are likely to activate metabotropic receptors having a slow and prolonged
      postsynaptic effect.

PMID- 9618550
TI  - Acoustic overstimulation increases outer hair cell Ca2+ concentrations and causes
      dynamic contractions of the hearing organ.
AB  - The dynamic responses of the hearing organ to acoustic overstimulation were
      investigated using the guinea pig isolated temporal bone preparation. The organ
      was loaded with the fluorescent Ca2+ indicator Fluo-3, and the cochlear electric
      responses to low-level tones were recorded through a microelectrode in the scala
      media. After overstimulation, the amplitude of the cochlear potentials decreased
      significantly. In some cases, rapid recovery was seen with the potentials
      returning to their initial amplitude. In 12 of 14 cases in which overstimulation
      gave a decrease in the cochlear responses, significant elevations of the
      cytoplasmic [Ca2+] in the outer hair cells were seen. [Ca2+] increases appeared
      immediately after terminating the overstimulation, with partial recovery taking
      place in the ensuing 30 min in some preparations. Such [Ca2+] changes were not
      seen in preparations that were stimulated at levels that did not cause an
      amplitude change in the cochlear potentials. The overstimulation also gave rise
      to a contraction, evident as a decrease of the width of the organ of Corti. The
      average contraction in 10 preparations was 9 microm (SE 2 microm). Partial or
      complete recovery was seen within 30-45 min after the overstimulation. The [Ca2+]
      changes and the contraction are likely to produce major functional alterations
      and consequently are suggested to be a factor contributing strongly to the loss
      of function seen after exposure to loud sounds.

PMID- 9618551
TI  - Differential roles of Ca2+/calmodulin-dependent kinases in posttetanic
      potentiation at input selective glutamatergic pathways.
AB  - The electrosensory lateral line lobe (ELL) of the electric fish Apteronotus
      leptorhynchus is a layered medullary region receiving electroreceptor input that
      terminates on basal dendrites of interneurons and projection (pyramidal) cells.
      The molecular layer of the ELL contains two distinct glutamatergic feedback
      pathways that terminate on the proximal (ventral molecular layer, VML) and distal
      (dorsal molecular layer) apical dendrites of pyramidal cells. Western blot
      analysis with an antibody directed against mammalian Ca2+/calmodulin-dependent
      kinase 2, alpha subunit (CaMK2alpha) recognized a protein of identical size in
      the brain of A. leptorhynchus. Immunohistochemistry demonstrated that CaMK2 alpha
      expression in the ELL was restricted to fibers and terminals in the VML.
      Posttetanic potentiation (PTP) could be readily elicited in pyramidal cells by
      stimulation of either VML or DML in brain slices of the ELL. PTP in the VML was
      blocked by extracellular application of a CaMK2 antagonist (KN62) while
      intracellular application of KN62 or a CaMK2 inhibitory peptide had no effect,
      consistent with the presynaptic localization of CaMK2 alpha in VML. PTP in the
      dorsal molecular layer was not affected by extracellular application of KN62.
      Anti-Hebbian plasticity has also been demonstrated in the VML, but was not
      affected by KN62. These results demonstrate that, while PTP can occur independent
      of CaMK2, it is, in some synapses, dependent on this kinase.

PMID- 9618552
TI  - Retinoic acid has light-adaptive effects on horizontal cells in the retina.
AB  - Ambient light conditions affect the morphology of synaptic elements within the
      cone pedicle and modulate the spatial properties of the horizontal cell receptive
      field. We describe here that the effects of retinoic acid on these properties are
      similar to those of light adaptation. Intraorbital injection of retinoic acid
      into eyes of dark-adapted carp that subsequently were kept in complete darkness
      results in the formation of numerous spinules at the terminal dendrites of
      horizontal cells, a typical feature of light-adapted retinae. The formation of
      these spinules during light adaptation is impaired in the presence of citral, a
      competitive inhibitor of the dehydrogenase responsible for the generation of
      retinoic acid in vivo. Intracellularly recorded responses of horizontal cells
      from dark-adapted eyecup preparations superfused with retinoic acid reveal
      typical light-adapted spatial properties. Retinoic acid thus appears to act as a
      light-signaling modulator. Its activity appears not to be at the transcriptional
      level because its action was not blocked by actinomycin.

PMID- 9618553
TI  - Neuronal coincidence detection by voltage-sensitive electrical synapses.
AB  - Coincidence detection is important for functions as diverse as Hebbian learning,
      binaural localization, and visual attention. We show here that extremely precise
      coincidence detection is a natural consequence of the normal function of
      rectifying electrical synapses. Such synapses open to bidirectional current flow
      when presynaptic cells depolarize relative to their postsynaptic targets and
      remain open until well after completion of presynaptic spikes. When multiple
      input neurons fire simultaneously, the synaptic currents sum effectively and
      produce a large excitatory postsynaptic potential. However, when some inputs are
      delayed relative to the rest, their contributions are reduced because the early
      excitatory postsynaptic potential retards the opening of additional voltage
      sensitive synapses, and the late synaptic currents are shunted by already opened
      junctions. These mechanisms account for the ability of the lateral giant neurons
      of crayfish to sum synchronous inputs, but not inputs separated by only 100
      microsec. This coincidence detection enables crayfish to produce reflex escape
      responses only to very abrupt mechanical stimuli. In light of recent evidence
      that electrical synapses are common in the mammalian central nervous system, the
      mechanisms of coincidence detection described here may be widely used in many
      systems.

PMID- 9618554
TI  - Bradykinin inhibits M current via phospholipase C and Ca2+ release from IP3
      sensitive Ca2+ stores in rat sympathetic neurons.
AB  - A variety of intracellular signaling pathways can modulate the properties of
      voltage-gated ion channels. Some of them are well characterized. However, the
      diffusible second messenger mediating suppression of M current via G protein
      coupled receptors has not been identified. In superior cervical ganglion neurons,
      we find that the signaling pathways underlying M current inhibition by B2
      bradykinin and M1 muscarinic receptors respond very differently to inhibitors.
      The bradykinin pathway was suppressed by the phospholipase C inhibitor U-73122,
      by blocking the IP3 receptor with pentosan polysulfate or heparin, and by
      buffering intracellular calcium, and it was occluded by allowing IP3 to diffuse
      into the cytoplasm via a patch pipette. By contrast, the muscarinic pathway was
      not disrupted by any of these treatments. The addition of bradykinin was
      accompanied by a [Ca2+]i rise with a similar onset and time to peak as the
      inhibition of M current. The M current inhibition and the rise of [Ca2+]i were
      blocked by depletion of Ca2+ internal stores by thapsigargin. We conclude that
      bradykinin receptors inhibit M current of sympathetic neurons by activating
      phospholipase C and releasing Ca2+ from IP3-sensitive Ca2+ stores, whereas
      muscarinic receptors do not use the phospholipase C pathway to inhibit M current
      channels.

PMID- 9618555
TI  - Role for G protein-coupled receptor kinase in agonist-specific regulation of mu
      opioid receptor responsiveness.
AB  - The G protein-coupled mu-opioid receptor (mu OR) mediates the physiological
      effects of endogenous opioid peptides as well as the structurally distinct opioid
      alkaloids morphine and etorphine. An intriguing feature of mu OR signaling is the
      differential receptor trafficking and desensitization properties following
      activation by distinct agonists, which have been proposed as possible mechanisms
      related to opioid tolerance. Here we report that the ability of distinct opioid
      agonists to differentially regulate mu OR internalization and desensitization is
      related to their ability to promote G protein-coupled receptor kinase (GRK)
      dependent phosphorylation of the mu OR. Although both etorphine and morphine
      effectively activate the mu OR, only etorphine elicits robust mu OR
      phosphorylation followed by plasma membrane translocation of beta-arrestin and
      dynamin-dependent receptor internalization. In contrast, corresponding to its
      inability to cause mu OR internalization, morphine is unable to either elicit mu
      OR phosphorylation or stimulate beta-arrestin translocation. However, upon the
      overexpression of GRK2, morphine gains the capacity to induce mu OR
      phosphorylation, accompanied by the rescue of beta-arrestin translocation and
      receptor sequestration. Moreover, overexpression of GRK2 also leads to an
      attenuation of morphine-mediated inhibition of adenylyl cyclase. These findings
      point to the existence of marked differences in the ability of different opioid
      agonists to promote mu OR phosphorylation by GRK. These differences may provide
      the molecular basis underlying the different analgesic properties of opioid
      agonists and contribute to the distinct ability of various opioids to induce drug
      tolerance.

PMID- 9618556
TI  - Modulation of an early step in the secretory machinery in hippocampal nerve
      terminals.
AB  - In hippocampal neurons, neurotransmitter release can be regulated by protein
      kinase A (PKA) through a direct action on the secretory machinery. To identify
      the site of PKA modulation, we have taken advantage of the ability of the
      neurotoxin Botulinum A to cleave the synaptic protein SNAP-25. Cleavage of this
      protein decreases the Ca2+ responsiveness of the secretory machinery by partially
      uncoupling Ca2+-sensing from fusion per se. This is expressed as a shift toward
      higher Ca2+ levels of the Ca2+ to neurotransmitter release relationship and as a
      perturbation of synaptic delay under conditions where secretion induced by the
      Ca2+-independent secretagogue ruthenium red is unimpaired. We find that SNAP-25
      cleavage also perturbs PKA-dependent modulation of secretion; facilitation of
      ruthenium red-evoked neurotransmitter release by the adenylyl cyclase activator
      forskolin is blocked completely after Botulinum toxin A action. Together with our
      observation that forskolin modifies the Ca2+ to neurotransmitter release
      relationship, our results suggest that SNAP-25 acts as a functional linker
      between Ca2+ detection and fusion and that PKA modulates an early step in the
      secretory machinery related to calcium sensing to facilitate synaptic
      transmission.

PMID- 9618557
TI  - Nedd4 mediates control of an epithelial Na+ channel in salivary duct cells by
      cytosolic Na+.
AB  - Epithelial Na+ channels are expressed widely in absorptive epithelia such as the
      renal collecting duct and the colon and play a critical role in fluid and
      electrolyte homeostasis. Recent studies have shown that these channels interact
      via PY motifs in the C terminals of their alpha, beta, and gamma subunits with
      the WW domains of the ubiquitin-protein ligase Nedd4. Mutation or deletion of
      these PY motifs (as occurs, for example, in the heritable form of hypertension
      known as Liddle's syndrome) leads to increased Na+ channel activity. Thus,
      binding of Nedd4 by the PY motifs would appear to be part of a physiological
      control system for down-regulation of Na+ channel activity. The nature of this
      control system is, however, unknown. In the present paper, we show that Nedd4
      mediates the ubiquitin-dependent down-regulation of Na+ channel activity in
      response to increased intracellular Na+. We further show that Nedd4 operates
      downstream of Go in this feedback pathway. We find, however, that Nedd4 is not
      involved in the feedback control of Na+ channels by intracellular anions.
      Finally, we show that Nedd4 has no influence on Na+ channel activity when the Na+
      and anion feedback systems are inactive. We conclude that Nedd4 normally mediates
      feedback control of epithelial Na+ channels by intracellular Na+, and we suggest
      that the increased Na+ channel activity observed in Liddle's syndrome is
      attributable to the loss of this regulatory feedback system.

PMID- 9618558
TI  - A release mechanism for stored ATP in ocular ciliary epithelial cells.
AB  - Purines can modify ciliary epithelial secretion of aqueous humor into the eye.
      The source of the purinergic agonists acting in the ciliary epithelium, as in
      many epithelial tissues, is unknown. We found that the fluorescent ATP marker
      quinacrine stained rabbit and bovine ciliary epithelia but not the nerve fibers
      in the ciliary bodies. Cultured bovine pigmented and nonpigmented ciliary
      epithelial cells also stained intensely when incubated with quinacrine. Hypotonic
      stimulation of cultured epithelial cells increased the extracellular ATP
      concentration by 3-fold; this measurement underestimates actual release as the
      cells also displayed ecto-ATPase activity. The hypotonically triggered increase
      in ATP was inhibited by the Cl--channel blocker 5-nitro-2-(3
      phenylpropylamino)benzoic acid (NPPB) in both cell types. In contrast, the P
      glycoprotein inhibitors tamoxifen and verapamil and the cystic fibrosis
      transmembrane conductance regulator (CFTR) blockers glybenclamide and
      diphenylamine-2-carboxylate did not affect ATP release from either cell type.
      This pharmacological profile suggests that ATP release is not restricted to P
      glycoprotein or the cystic fibrosis transmembrane conductance regulator, but can
      proceed through a route sensitive to NPPB. ATP release also was triggered by
      ionomycin through a different NPPB-insensitive mechanism, inhibitable by the
      calcium/calmodulin-activated kinase II inhibitor KN-62. Thus, both layers of the
      ciliary epithelium store and release ATP, and purines likely modulate aqueous
      humor flow by paracrine and/or autocrine mechanisms within the two cell layers of
      this epithelium.

PMID- 9618559
TI  - The role of transmembrane domain 2 in cation transport by the Na-K-Cl
      cotransporter.
AB  - The human and shark Na-K-Cl cotransporters (NKCC), although 74% identical in
      amino acid sequence, exhibit marked differences in ion transport and bumetanide
      binding. We have utilized shark-human chimeras of NKCC1 to search for regions
      that confer the kinetic differences. Two chimeras (hs3.1 and its reverse sh3.1)
      with a junction point located at the beginning of the third transmembrane domain
      were examined after stable transfection in HEK-293 cells. Each carried out
      bumetanide-sensitive 86Rb influx with cation affinities intermediate between
      shark and human cotransporters. In conjunction with the previous finding that the
      N and C termini are not responsible for differences in ion transport, the current
      observations identify the second transmembrane domain as playing an important
      role. Site-specific mutagenesis of two pairs of residues in this domain revealed
      that one pair is indeed involved in the difference in Na affinity, and a second
      pair is involved in the difference in Rb affinity. Substitution of the same
      residues with corresponding residues from NKCC2 or the Na-Cl cotransporter
      resulted in cation affinity changes, consistent with the hypothesis that
      alternative splicing of transmembrane domain 2 endows different versions of NKCC2
      with unique kinetic behaviors. None of the changes in transmembrane domain 2 was
      found to substantially affect Km(Cl), demonstrating that the affinity difference
      for Cl is specified by the region beyond predicted transmembrane domain 3.
      Finally, unlike Cl, bumetanide binding was strongly affected by shark-human
      replacement of transmembrane domain 2, indicating that the bumetanide-binding
      site is not the same as the Cl-binding site.

PMID- 9618560
TI  - MgATP activates the beta cell KATP channel by interaction with its SUR1 subunit.
AB  - ATP-sensitive potassium (KATP) channels in the pancreatic beta cell membrane
      mediate insulin release in response to elevation of plasma glucose levels. They
      are open at rest but close in response to glucose metabolism, producing a
      depolarization that stimulates Ca2+ influx and exocytosis. Metabolic regulation
      of KATP channel activity currently is believed to be mediated by changes in the
      intracellular concentrations of ATP and MgADP, which inhibit and activate the
      channel, respectively. The beta cell KATP channel is a complex of four Kir6.2
      pore-forming subunits and four SUR1 regulatory subunits: Kir6.2 mediates channel
      inhibition by ATP, whereas the potentiatory action of MgADP involves the
      nucleotide-binding domains (NBDs) of SUR1. We show here that MgATP (like MgADP)
      is able to stimulate KATP channel activity, but that this effect normally is
      masked by the potent inhibitory effect of the nucleotide. Mg2+ caused an apparent
      reduction in the inhibitory action of ATP on wild-type KATP channels, and MgATP
      actually activated KATP channels containing a mutation in the Kir6.2 subunit that
      impairs nucleotide inhibition (R50G). Both of these effects were abolished when
      mutations were made in the NBDs of SUR1 that are predicted to abolish MgATP
      binding and/or hydrolysis (D853N, D1505N, K719A, or K1384M). These results
      suggest that, like MgADP, MgATP stimulates KATP channel activity by interaction
      with the NBDs of SUR1. Further support for this idea is that the ATP sensitivity
      of a truncated form of Kir6.2, which shows functional expression in the absence
      of SUR1, is unaffected by Mg2+.

PMID- 9618561
TI  - Evidence of high expression of peptidylglycine alpha-amidating monooxygenase in
      the rat uterus: estrogen regulation.
AB  - In the present study, high levels of peptidylglycine alpha-amidating
      monooxygenase (PAM), which catalyzes the two-step formation of bioactive alpha
      amidated peptides from their glycine-extended precursors, have been found in the
      uterus. Expression of PAM was evaluated in the uterus of intact cycling adult
      female rats and after experimental manipulation of the estrogen status of the
      rats. During the estrous cycle, PAM mRNA levels exhibited striking changes
      inversely related to the physiological variations of plasma estrogen levels. The
      levels of PAM transcripts changed markedly during the estrous cycle, reaching the
      highest levels at metestrus. There was a 15-fold increase in the abundance of PAM
      mRNA between metestrus and proestrus. Chronic treatment of ovariectomized rats
      with 17beta-estradiol decreased PAM mRNA levels to values comparable with those
      found in intact rats at proestrus. Progesterone was without effect on PAM mRNA
      levels, indicating that the effect was specific for estradiol. In situ
      hybridization studies were conducted to determine the tissue disposition and cell
      types expressing PAM. High levels of PAM mRNA were localized in the endometrium
      at the level of luminal and glandular cells. A weak signal was observed in
      stromal cells, and the myometrium cells were negative. 17beta-Estradiol treatment
      induced an overall decrease of the hybridization signal, as compared with
      ovariectomized rats. These results demonstrate the presence of high levels of PAM
      in the uterus and indicate that estrogens are involved in regulating the
      expression of the enzyme in this tissue. However, the present study provides no
      information regarding whether this regulation takes place at the level of
      transcription or influences mRNA stability.

PMID- 9618562
TI  - High temperature promotes auxin-mediated hypocotyl elongation in Arabidopsis.
AB  - Physiological studies with excised stem segments have implicated the plant
      hormone indole-3-acetic acid (IAA or auxin) in the regulation of cell elongation.
      Supporting evidence from intact plants has been somewhat more difficult to
      obtain, however. Here, we report the identification and characterization of an
      auxin-mediated cell elongation growth response in Arabidopsis thaliana. When
      grown in the light at high temperature (29 degreesC), Arabidopsis seedlings
      exhibit dramatic hypocotyl elongation compared with seedlings grown at 20
      degreesC. This temperature-dependent growth response is sharply reduced by
      mutations in the auxin response or transport pathways and in seedlings containing
      reduced levels of free IAA. In contrast, mutants deficient in gibberellin and
      abscisic acid biosynthesis or in ethylene response are unaffected. Furthermore,
      we detect a corresponding increase in the level of free IAA in seedlings grown at
      high temperature, suggesting that temperature regulates auxin synthesis or
      catabolism to mediate this growth response. Consistent with this possibility,
      high temperature also stimulates other auxin-mediated processes including auxin
      inducible gene expression. Based on these results, we propose that growth at high
      temperature promotes an increase in auxin levels resulting in increased hypocotyl
      elongation. These results strongly support the contention that endogenous auxin
      promotes cell elongation in intact plants.

PMID- 9618563
TI  - Transgene organization in rice engineered through direct DNA transfer supports a
      two-phase integration mechanism mediated by the establishment of integration hot
      spots.
AB  - Organization of transgenes in rice transformed through direct DNA transfer
      strongly suggests a two-phase integration mechanism. In the "preintegration"
      phase, transforming plasmid molecules (either intact or partial) are spliced
      together. This gives rise to rearranged transgenic sequences, which upon
      integration do not contain any interspersed plant genomic sequences.
      Subsequently, integration of transgenic DNA into the host genome is initiated.
      Our experiments suggest that the original site of integration acts as a hot spot,
      facilitating subsequent integration of successive transgenic molecules at the
      same locus. The resulting transgenic locus may have plant DNA separating the
      transgenic sequences. Our data indicate that transformation through direct DNA
      transfer, specifically particle bombardment, generally results in a single
      transgenic locus as a result of this two-phase integration mechanism. Transgenic
      plants generated through such processes may, therefore, be more amenable to
      breeding programs as the single transgenic locus will be easier to characterize
      genetically. Results from direct DNA transfer experiments suggest that in the
      absence of protein factors involved in exogenous DNA transfer through
      Agrobacterium, the qualitative and/or quantitative efficiency of transformation
      events is not compromised. Our results cast doubt on the role of Agrobacterium
      vir genes in the integration process.

PMID- 9618564
TI  - A role for jasmonate in pathogen defense of Arabidopsis.
AB  - To investigate the role of jasmonate in the defense of plants against fungal
      pathogens, we have studied a mutant of Arabidopsis, fad3-2 fad7-2 fad8, that
      cannot accumulate jasmonate. Mutant plants were extremely susceptible to root rot
      caused by the fungal root pathogen Pythium mastophorum (Drechs.), even though
      neighboring wild-type plants were largely unaffected by this fungus. Application
      of exogenous methyl jasmonate substantially protected mutant plants, reducing the
      incidence of disease to a level close to that of wild-type controls. A similar
      treatment with methyl jasmonate did not protect the jasmonate-insensitive mutant
      coi1 from infection, showing that protective action of applied jasmonate against
      P. mastophorum was mediated by the induction of plant defense mechanisms rather
      than by a direct antifungal action. Transcripts of three jasmonate-responsive
      defense genes are induced by Pythium challenge in the wild-type but not in the
      jasmonate-deficient mutant. Pythium species are ubiquitous in soil and root
      habitats world-wide, but most (including P. mastophorum) are considered to be
      minor pathogens. Our results indicate that jasmonate is essential for plant
      defense against Pythium and, because of the high exposure of plant roots to
      Pythium inoculum in soil, may well be fundamental to survival of plants in
      nature. Our results further indicate that the fad3-2 fad7-2 fad8 mutant is an
      appropriate genetic model for studying the role of this important signaling
      molecule in pathogen defense.

PMID- 9618565
TI  - The making of the architecture of the plant cell wall: how cells exploit
      geometry.
AB  - Cell wall deposition is a key process in the formation, growth, and
      differentiation of plant cells. The most important structural components of the
      wall are long cellulose microfibrils, which are synthesized by synthases embedded
      in the plasma membrane. A fundamental question is how the microfibrils become
      oriented during deposition at the plasma membrane. The current textbook
      explanation for the orientation mechanism is a guidance system mediated by
      cortical microtubules. However, too many contraindications are known in secondary
      cell walls for this to be a universal mechanism, particularly in the case of
      helicoidal arrangements, which occur in many situations. An additional
      construction mechanism involves liquid crystalline self-assembly [A. C. Neville
      (1993) Biology of Fibrous Composites: Development Beyond the Cell Membrane
      (Cambridge Univ. Press, Cambridge, U.K.)], but the required amount of bulk
      material that is able to equilibrate thermally is not normally present at any
      stage of the wall deposition process. Therefore, we have asked whether the
      complex ordered texture of helicoidal cell walls can be formed in the absence of
      direct cellular guidance mechanisms. We propose that they can be formed by a
      mechanism that is based on geometrical considerations. It explains the genesis of
      the complicated helicoidal texture and shows that the cell has intrinsic,
      versatile tools for creating a variety of textures. A compelling feature of the
      model is that local rules generate global order, a typical phenomenon of life.

PMID- 9618566
TI  - Identification of a family of zinc transporter genes from Arabidopsis that
      respond to zinc deficiency.
AB  - Millions of people worldwide suffer from nutritional imbalances of essential
      metals like zinc. These same metals, along with pollutants like cadmium and lead,
      contaminate soils at many sites around the world. In addition to posing a threat
      to human health, these metals can poison plants, livestock, and wildlife.
      Deciphering how metals are absorbed, transported, and incorporated as protein
      cofactors may help solve both of these problems. For example, edible plants could
      be engineered to serve as better dietary sources of metal nutrients, and other
      plant species could be tailored to remove metal ions from contaminated soils. We
      report here the cloning of the first zinc transporter genes from plants, the
      ZIP1, ZIP2, and ZIP3 genes of Arabidopsis thaliana. Expression in yeast of these
      closely related genes confers zinc uptake activities. In the plant, ZIP1 and ZIP3
      are expressed in roots in response to zinc deficiency, suggesting that they
      transport zinc from the soil into the plant. Although expression of ZIP2 has not
      been detected, a fourth related Arabidopsis gene identified by genome sequencing,
      ZIP4, is induced in both shoots and roots of zinc-limited plants. Thus, ZIP4 may
      transport zinc intracellularly or between plant tissues. These ZIP proteins
      define a family of metal ion transporters that are found in plants, protozoa,
      fungi, invertebrates, and vertebrates, making it now possible to address
      questions of metal ion accumulation and homeostasis in diverse organisms.

PMID- 9618567
TI  - The tobacco wounding-activated mitogen-activated protein kinase is encoded by
      SIPK.
AB  - It has been demonstrated that both salicylic acid and fungal elicitors activate a
      48-kDa mitogen-activated protein kinase termed salicylic acid-induced protein
      kinase (SIPK) in tobacco suspension cells. Here, we show that infiltration of
      these agents into tobacco leaves also activates SIPK. Of particular interest,
      infiltration of water alone activated a kinase of the same size, possibly because
      of wounding and/or osmotic stresses. The kinetics of kinase activation, however,
      differ for these different treatments. Various mechanical stresses, including
      cutting and wounding by abrasion, also activated a 48-kDa kinase. By using an
      immune-complex kinase assay with antibodies specific for SIPK or wounding-induced
      protein kinase, we demonstrate that this wounding-activated 48-kDa kinase is
      SIPK, rather than wounding-induced protein kinase, as reported [Seo, S., Okamoto,
      M., Seto, H., Ishizuka, K., Sano, H. & Ohashi, Y. (1995) Science 270, 1988-1992].
      Activation of SIPK after wounding was associated with tyrosine phosphorylation
      but not with increases in SIPK mRNA or protein levels. Thus, the same mitogen
      activated protein kinase, SIPK, appears to facilitate signaling for two distinct
      pathways that lead to disease resistance responses and wounding responses.

PMID- 9618569
TI  - Non-invasive estimation of the net influx constant using the standardized uptake
      value for quantification of FDG uptake of tumours.
AB  - To reduce the variability of the standardized uptake value (SUV) which is widely
      used to evaluate 2-[18F]fluoro-2-deoxy-d-glucose (FDG) uptake by neoplasms, net
      influx constant (Ki) was derived from SUV. The relationship Ki=SUV.kp.V0, where
      kp is the plasma clearance rate and V0 is the initial distribution volume of FDG,
      was utilized. A total of 71 plasma input functions were measured up to 60 min
      after intravenous injection of FDG in 55 patients and were analysed to obtain kp
      and V0. SUV and V0 were calculated based on either body weight or body surface
      area. To validate the Ki estimation, another group of eight patients with
      squamous cell carcinoma of the head and neck was included. Parametric images of
      the net influx constant were obtained by Patlak graphical analysis of dynamic
      positron emission tomography (PET) data and measured plasma input function. V0
      based on body weight was 0.1627+/-0.0329 (ml/g) and showed a weak negative
      correlation with body weight (y=0.23356-0.00138x, r=0.591). V0 based on body
      surface area was 5540+/-871 (ml/m2) and had no significant correlation with body
      weight. kp at 50 min post injection was 0. 03272+/-0.00243 (1/min), and had no
      correlation with the plasma glucose concentration. A highly significant positive
      correlation was noted between true Ki and estimated Ki based on both body weight
      (y=0.0033+1.0371x, r2=0.897), and body surface area (y=0.0033+1. 0351x,
      r2=0.926). Ki, a better indicator of FDG uptake by tumour than SUV, is derivable
      non-invasively. Quantification of FDG uptake by Ki will aid standardization of
      diagnostic criteria of FDG PET oncology.

PMID- 9618568
TI  - Social stress and the reactivation of latent herpes simplex virus type 1.
AB  - Psychological stress is thought to contribute to reactivation of latent herpes
      simplex virus (HSV). Although several animal models have been developed in an
      effort to reproduce different pathogenic aspects of HSV keratitis or labialis,
      until now, no good animal model existed in which application of a psychological
      laboratory stressor results in reliable reactivation of the virus. Reported
      herein, disruption of the social hierarchy within colonies of mice increased
      aggression among cohorts, activated the hypothalamic-pituitary-adrenal axis, and
      caused reactivation of latent HSV type 1 in greater than 40% of latently infected
      animals. However, activation of the hypothalamic-pituitary-adrenal axis using
      restraint stress did not activate the latent virus. Thus, the use of social
      stress in mice provides a good model in which to investigate the neuroendocrine
      mechanisms that underlie behaviorally mediated reactivation of latent
      herpesviruses.

PMID- 9618570
TI  - Estimation of absorbed dose for 2-[F-18]fluoro-2-deoxy-D-glucose using whole-body
      positron emission tomography and magnetic resonance imaging.
AB  - The purpose of this study was to measure the cumulated activity and absorbed dose
      in organs after intravenous administration of 2-[F-18]fluoro-2-deoxy-D-glucose
      (18F-FDG) using whole-body positron emission tomography (PET) and magnetic
      resonance imaging (MRI). Whole-body dynamic emission scans for 18F-FDG were
      performed in six normal volunteers after transmission scans. The total activity
      of a source organ was obtained from the activity concentration of the organ
      measured by whole-body PET and the volume of that organ measured by whole-body T1
      weighted MRI. The cumulated activity of each source organ was calculated from the
      time-activity curve. Absorbed doses to the individuals were estimated by the MIRD
      (medical internal radiation dosimetry) method using S-values adjusted to the
      individuals. Another calculation of cumulated activities and absorbed doses was
      performed using the organ volumes from the MIRD phantom and the "Japanese
      reference man" to investigate the discrepancy of actual individual results
      against the phantom results. The cumulated activities of 18 source organs were
      calculated, and absorbed doses of 27 target organs estimated. Among the target
      organs, bladder wall, brain and kidney received the highest doses for the above
      three sets of organ volumes. Using measured individual organ volumes, the average
      absorbed doses for those organs were found to be 3.1x10(-1), 3.7x10(-2) and
      2.8x10(-2) mGy/MBq, respectively. The mean effective doses in this study for
      individuals of average body weight (64.5 kg) and the MIRD phantom of 70 kg were
      the same, i.e. 2.9x10(-2) mSv/MBq, while for the Japanese reference man of 60 kg
      the effective dose was 2.1x10(-2) mSv/MBq. The results for measured organ volumes
      derived from MRI were comparable to those obtained for organ volumes from the
      MIRD phantom. Although this study considered 18F-FDG, combined use of whole-body
      PET and MRI might be quite effective for improving the accuracy of estimations of
      the cumulated activity and absorbed dose of positron-labelled
      radiopharmaceuticals.

PMID- 9618571
TI  - How to obtain high-accuracy image registration: application to movement
      correction of dynamic positron emission tomography data.
AB  - When registering dynamic positron emission tomography (PET) sequences, the time
      dependent changes in uptake pattern prevent registration of all frames to the
      first frame in a straightforward manner. Instead, a sequential registration of
      each frame to its predecessor may be used, provided the registration algorithm is
      completely free of bias. It is shown that most existing algorithms introduce a
      bias, the size of which depends on the pixel size and the signal-to-noise ratio
      of the data. The bias is introduced by the pixelisation of the underlying
      continuous process. All existing cost-functions are more or less sensitive to
      noise, and the noise reduction resulting from translating one image set relative
      to the other means that a small movement will always be detected in the cases
      where no actual movement has occurred. The problem is solved by an initial
      resampling of the reference volume into a representation with another image and
      pixel size. If the new representation is sensibly chosen it means that all
      possible transforms applied to the other image volume will yield approximately
      the same noise reduction, thereby removing the source of the bias. The described
      effect is demonstrated on phantom data, and its impact is shown on human data.

PMID- 9618572
TI  - Gated SPET myocardial perfusion acquisition within 5 minutes using focussing
      collimators and a three-head gamma camera.
AB  - Short acquisition protocols for gated single-photon emission tomography (SPET)
      myocardial perfusion imaging are desirable for sequential imaging to evaluate the
      myocardial response during pharmacological intervention. In this study a less
      than 5 min gated SPET acquisition protocol is proposed. Perfusion characteristics
      (defect severity) and left ventricular ejection fraction (LVEF), end-diastolic
      and end-systolic volumes (EDV, ESV), wall motion (WM) and wall thickening (WT)
      were calculated, checked for reproducibility and compared with data obtained
      using a standard gated SPET acquisition protocol. Gated SPET images were recorded
      in 20 patients starting 60 min after the administration of 925 MBq technetium-99m
      tetrofosmin at rest. The 5 min gated SPET studies were acquired with a three-head
      camera equipped with Cardiofocal collimators. This protocol was repeated twice.
      In addition gated SPET studies were acquired according to a standard protocol
      using parallel-hole collimators. The severity of perfusion defects was quantified
      on polar maps using the non-gated image data and a normal database. LVEF, EDV,
      ESV, WM and WT were calculated from the gated images. The agreement between 5-min
      and standard gated SPET acquisitions was excellent for all investigated
      parameters. The reproducibility of repeated 5-min acquisitions for the
      quantification of perfusion defect severity was excellent (r=0.97). The agreement
      for segmental WT scores between repeated 5-min gated SPET acquisitions was good:
      kappa=0.71; major differences in segmental classification were observed in 2.5%.
      For WM a good agreement was found for segments with a tracer uptake >/=30% of the
      maximum: kappa=0.65, major differences =7.7%. Excellent reproducibility was found
      for LVEF, EDV and ESV measurements: r=0.97, 0.99 and 0.99, respectively. It is
      concluded that fast gated SPET perfusion studies acquired in less than 5 min
      yield accurate and reproducible measurements of myocardial perfusion and function
      (global and regional). In addition the results obtained with the 5-min gated SPET
      protocol correlate well with those obtained using a standard acquisition
      protocol.

PMID- 9618573
TI  - Prediction of post-revascularization functional recovery of asynergic myocardium
      using quantitative thallium-201 rest-redistribution tomography: has the reverse
      redistribution pattern an independent significance?
AB  - The significance of reverse redistribution on rest-redistribution thallium-201
      myocardial scintigraphy is unclear. Previous studies suggested that reverse
      redistribution segments with normal resting activity include viable myocardium,
      whilst resting defects with further worsening correspond to scar. We evaluated
      whether reverse redistribution has an independent significance for the prediction
      of post-revascularization recovery, particularly as compared with the
      quantification of redistribution activity. We studied 26 coronary artery disease
      patients with left ventricular dysfunction, who underwent 201Tl rest
      redistribution single-photon emission tomography (SPET) and echocardiography
      before revascularization. Viability was defined by the detection of wall motion
      improvement on follow-up echocardiography. 201Tl activity was considered normal
      if >/=80%, moderately reduced if <80% but >/=50%, and severely decreased if <50%.
      Reverse redistribution was defined as a defect in redistribution images with
      >/=10% decrease in relative 201Tl activity compared with the resting value.
      Reverse redistribution was detected in 33 segments (10%). Baseline dysfunction
      was equally observed in the reverse redistribution and in the non-reverse
      redistribution segments (64% vs 56%, P=0.40) and the rate of asynergic segments
      with post-revascularization recovery was not different between the two groups
      (33% vs 54%, P=0.11). The rate of functional recovery in redistribution defects
      without reverse redistribution was 53% in moderate and 30% in severe defects; the
      corresponding values for the reverse redistribution segments were 50% and 27%
      (all non-significant versus non-reverse redistribution segments). For the
      prediction of post-revascularization recovery in asynergic segments, the
      detection of reverse redistribution on rest-redistribution 201Tl SPET does not
      add any information to the quantitative analysis of redistribution activity.

PMID- 9618574
TI  - A technetium-99m hexamethylpropylene amine oxime brain single-photon emission
      tomography study in adolescent patients with major depressive disorder.
AB  - We have not encountered any brain single-photon emission tomography (SPET) study
      performed in adolescent depressed patients in the literature. Therefore, we used
      technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) brain SPET in
      adolescent patients with major depressive disorder (MDD) to examine the possible
      changes in cerebral perfusion and the possible association between perfusion
      indices and clinical variables. Fourteen adolescent out-patients (nine females,
      five males; mean+/-SD age: 13.11+/-1.43 years; range: 11-15 years) fulfilling the
      DSM-IV criteria for MDD and 11 age-matched healthy control subjects (six females,
      five males; mean+/-SD age: 13.80+/-1.60 years; range: 12-15 years) were included
      in the study. 99Tc-HMPAO brain SPET was performed twice in the patient group and
      once in the control group. The first SPET investigation was performed under non
      medicated conditions and the second was performed after depressive symptoms had
      subsided. A relative perfusion index (PI) was calculated as the ratio of regional
      cortical activity to the whole brain activity. We found significant differences
      between the PI values of the untreated depressed patients and those of the
      controls, indicating relatively reduced perfusion in the left anterofrontal and
      left temporal cortical areas. No significant differences in regional PI values
      were found between the remitted depressed patients and the controls. Our study
      suggests that adolescent patients with MDD may have regional cerebral blood flow
      deficits in frontal regions and a greater anterofrontal right-left perfusion
      asymmetry compared with normal subjects. The fact that these abnormalities in
      perfusion indices have a trend toward normal values with symptomatic improvement
      suggests that they may be state-dependent markers for adolescent MDD.

PMID- 9618575
TI  - Is brain uptake of leptin in vivo saturable and reduced by fasting?
AB  - Leptin is a peptide hormone produced by adipocytes which provides a negative
      feedback signal to control the amount of body fat. The action of leptin on food
      intake and weight loss is thought to be mediated by interaction with its
      hypothalamic receptor. We examined the biodistribution and brain uptake of
      radioiodinated leptin (123I-leptin) by dynamic gamma imaging in six anaesthetized
      New Zealand white rabbits. Leptin uptake was seen in the brain, lungs, liver and
      kidneys. In the brain, increase in radioactivity as a function of time was seen
      in the choroid plexus area. The choroid plexus to brain radioactivity ratio
      (CP/BR) was used as the target to background ratio. The CP/BR ratio increased up
      to approximately 40-60 min, after which a steady state in CP/BR was achieved. The
      steady state uptake ratio was higher in the rabbits that had fasted for only 6-8
      h before the experiment (CP/BR approximately 2.5) than in those that had fasted
      for 25-27 h before the experiment (CP/BR approximately 1.8). Thus, leptin uptake
      in vivo occurs in the choroid plexus region of the brain and in the lungs, kidney
      and the liver. The uptake of leptin in the choroid plexus appears to be
      saturable, as indicated by the achieved steady state in the CP/BR radioactivity
      curve 40-60 min following 123I-leptin injection. The lower steady state CP/BR
      after prolonged fasting may be the result of the downregulation of leptin
      receptors in the choroid plexus.

PMID- 9618577
TI  - Therapeutic implications of thymic uptake of radioiodine in thyroid carcinoma.
AB  - The management of 38 consecutive patients with differentiated thyroid carcinoma
      in the period 1991-1996, who each received at least one therapy dose of iodine
      131, was reviewed, looking in particular at those in whom anterior mediastinal
      uptake was demonstrated on scans taken 3 and 7 days post-therapy. Such activity
      was noted in ten patients. On the basis of clinical follow-up, thyroglobulin
      measurement and radiological and other scintigraphic imaging, in nine of the ten
      patients the anterior mediastinal activity was attributed to physiological thymic
      uptake. Of those nine, all were under 50 years of age; seven were considered
      disease free, one had residual disease in the neck and one had distant
      metastases. Physiological uptake by the thymus was more prominent on the 7-day
      scans and in patients with low tumour volumes. For appropriate patient management
      it is essential to recognise that physiological uptake of 131I by the thymus in
      patients under 50 years of age is a potential cause of false-positive therapy
      scans.

PMID- 9618576
TI  - Pentavalent rhenium-188 dimercaptosuccinic acid for targeted radiotherapy:
      synthesis and preliminary animal and human studies.
AB  - Pentavalent rhenium-188 dimercaptosuccinic acid [188Re(V)DMSA] is a beta-emitting
      analogue of 99mTc(V)DMSA, a tracer that is taken up in a variety of tumours and
      bone metastases. The aim of this study was to develop the kit-based synthesis of
      the agent on a therapeutic scale, to assess its stability in vivo, and to obtain
      preliminary biodistribution and dosimetry estimates, prior to evaluation of its
      potential as a targeted radiotherapy agent. The organ distribution of 188Re in
      mice was determined 2 h after injection of 3 MBq 188Re(V)DMSA prepared from
      eluate from a 188W/188Re generator. Three patients with cancer of the prostate
      and three with cancer of the bronchus, all with bone metastases confirmed with a
      standard 99mTc-hydroxymethylene diphosphonate (99mTc-HDP) scan, were given 370
      MBq 188Re(V)DMSA and imaged at 3 h and 24 h using the 155-keV gamma-photon (15%).
      Blood and urine samples were collected to determine clearance and to analyse the
      speciation of 188Re. Organ residence times were estimated from the scans, and
      used to estimate radiation doses using MIRDOSE 3. In mice, 188Re(V)DMSA was
      selective for bone and kidney. In patients, it showed selectivity for bone
      metastases (particularly those from prostate carcinoma) and kidney, but uptake in
      normal bone was not significantly greater than in surrounding soft tissues. Of
      the normal tissues the kidneys received the highest radiation dose (0.5-1.3
      mGy/MBq). The images were strongly reminiscent of 99mTc(V)DMSA scans in similar
      patients. High-performance liquid chromatography analysis of blood and urine
      showed no evidence of 188Re in any chemical form other than 188Re(V)DMSA up to 24
      h. In conclusion, 188Re(V)DMSA and its 186Re analogue warrant further clinical
      assessment as generator/kit-derived agents for treatment of painful bone
      metastases. These agents should also be assessed in medullary thyroid carcinoma
      and other soft tissue tumours which have been shown to accumulate 99mTc(V)DMSA.

PMID- 9618578
TI  - Estimation of internal absorbed dose of L-[methyl-11C]methionine using whole-body
      positron emission tomography.
AB  - L-[Methyl-11C]-methionine (11C-methionine) is proposed as a useful radiotracer
      for tumour diagnosis. Human biodistribution data of cumulated activities and
      absorbed doses estimated by the MIRD (medical internal radiation dosimetry)
      method for 11C-methionine are not available in the literature. In this study we
      measured the organ activity for 11C-methionine by using whole-body positron
      emission tomography (PET) and estimated the absorbed doses to 25 organs by the
      MIRD method. Whole-body dynamic PET scans were performed on five normal
      volunteers to measure the time course of the organ activity concentration
      (activity/volume) after intravenous administration of 11C-methionine. Cumulated
      activities of the ten source organs were calculated from the time-activity
      curves, obtained from the dynamic PET data. Absorbed dose estimates were
      performed by the MIRD method for the Caucasian reference man and for the Japanese
      reference man. The organs which received the highest absorbed doses for the
      Caucasian reference man were found to be the bladder wall (2.7x10(-2) mGy/MBq),
      the pancreas (1.9x10(-2) mGy/ MBq), the liver (1.8x10(-2) mGy/MBq) and the kidney
      (1.1x10(-2) mGy/MBq). The effective doses for the Caucasian reference man and the
      Japanese reference man were calculated as 5.2x10(-3) and 5.0x10(-3) mSv/MBq,
      respectively.

PMID- 9618579
TI  - Comparison of bone single-photon emission tomography and planar imaging in the
      detection of vertebral metastases in patients with back pain.
AB  - Bone scan has long been considered to be an important diagnostic test in
      searching for bone metastases. However, considerable difficulty is encountered in
      the vertebral region due to the complexity of structures and the fact that other
      benign lesions, especially degenerative changes, are very common there. Single
      photon emission tomography (SPET) has been reported to be useful in the
      differentiation of benign from malignant conditions. Here we report our
      experience with bone SPET in the diagnosis of vertebral metastases. This is a
      retrospective study of technetium-99m methylene diphosphonate (MDP) bone scans in
      174 consecutive patients who were referred for the investigation of back pain in
      our department. MDP planar and SPET images were obtained. Of teh 174 patients, 98
      had a known history of malignant tumours. The diagnosis of vertebral metastasis
      was made on the basis of the patients' clinical histories and the findings with
      other imaging techniques such as magnetic resonance imaging, computed tomography
      or follow-up bone scan. We found that the presence of pedicle involvement as seen
      on SPET was an accurate diagnostic criterion of vertebral metastasis. SPET had a
      sensitivity of 87%, a specificity of 91%, a positive predictive value of 82%, a
      negative predictive value of 94% and an accuracy of 90%. On the other hand,
      planar study had a sensitivity of 74%, a specificity of 81%, a positive
      predictive value of 64%, a negative predictive value of 88% and an accuracy of
      79% in diagnosing vertebral metastasis. Except with regard to the negative
      predictive value, SPET performed statistically better than planar imaging. Only
      9/147 (6.4%) lesions involving the vertebral body alone and 3/49 (6.1%) lesions
      involving facet joints alone were subsequently found to be metastases. We
      conclude that bone SPET is an accurate diagnostic test for the detection of
      vertebral metastases and is superior to planar imaging in this respect.

PMID- 9618580
TI  - Radionuclide imaging of neuroendocrine tumours: biological basis and diagnostic
      results.
AB  - Neuroendocrine tumours have been defined as APUD-omas in the past by authors who
      identified common metabolic characteristics (amine precursor uptake and
      decarboxylation) in a group of tumours thought to originate from cells of the
      neural crest and to be able to produce biogenic amines. The identification of
      neuroendocrine tumours with APUD-omas was not confirmed by subsequent
      investigators. At present it is known that a group of neuroendocrine tumours
      derive from pluripotent stem cells or from differentiated neuroendocrine cells,
      and that they have a particular pattern of histology due to the presence of some
      secretory products and particular cytoplasmic proteins. Many radiopharmaceuticals
      have been successfully used in nuclear medicine to visualise neuroendocrine
      tumours; most of them are based on specific uptake mechanisms, but some are non
      specific probes. This review is focussed on the clinical application of
      radiolabelled metaiodobenzylguanidine, indium-111 pentetreotide, radiolabelled
      vasointestinal peptide, radiolabelled monoclonal antibodies and positron-emitting
      tracers. While many different types of neuroendocrine tumours are identified
      today, only the most common histotypes and those tumours of major relevance for
      nuclear medicine are considered in this review (anterior pituitary tumours and
      neuroblastoma are excluded). New knowledge in molecular biology, relevant
      biological and histological patterns, and the physiological and clinical
      behaviour are described for neuroendocrine tumours of the lung, tumours of the
      gastroenteropancreatic tract, medullary thyroid carcinoma, tumours of sympatho
      adrenal lineage, and multiple endocrine neoplasia. The nuclear medicine results
      in diagnostic imaging are presented, and the major comparative studies with
      different tracers are reported. The study of further possible diagnostic
      approaches addressing the biological characteristics of these tumours could open
      the way to various new therapeutic options.

PMID- 9618581
TI  - Supernumerary chromosomes in filamentous fungi.
AB  - Within a fungal species, a subset of individuals may have more than the minimal
      complement of chromosomes. If the extra chromosomes are composed primarily of DNA
      not found in all representatives of the species, they are most appropriately
      referred to as supernumerary chromosomes. The patterns of repeated DNA sequences
      on certain supernumerary chromosomes suggest that they have a different
      evolutionary history from the essential chromosomes in the same genome.
      Supernumerary chromosomes can carry functional genes and, in at least two fungal
      species, genes on such chromosomes play important roles in host-pathogen
      interactions. Supernumerary chromosomes that confer an adaptive advantage in
      certain habitats, such as the ability to cause disease on a specific host, may be
      referred to as "conditionally dispensable" chromosomes in order to reflect their
      importance in some, but not all, growth conditions. In addition to describing the
      structural and functional characteristics of known supernumerary chromosomes in
      fungi, this review discusses the relative merits of the terms that have been used
      to describe them, and establishes experimental criteria for their identification.

PMID- 9618582
TI  - Protein synthesis by isolated pea mitochondria is dependent on the activity of
      respiratory complex II.
AB  - In isolated pea (Pisum sativum L.) mitochondria incorporation of 35S-methionine
      into newly synthesised proteins was influenced by the presence of site-specific
      inhibitors of the respiratory electron-transport chain. These effects were not
      produced by changes in the rate of respiratory electron transport itself nor by
      changes in ATP concentration. Protein synthesis was inhibited by inhibitors of
      ubiquinone reduction but not by inhibitors of ubiquinol oxidation. By the use of
      additional inhibitors at specific sites of the respiratory chain, different
      oxidation-reduction states were obtained for the different complexes in the
      electron-transport chain. It was found that electron transport through
      succinate:ubiquinone oxidoreductase (respiratory complex II) was specifically
      required for protein synthesis, even when all the other conditions for protein
      synthesis were satisfied. We suggest that a subunit of complex II, or a component
      closely associated with complex II, is involved in a regulatory system that
      couples electron transport to protein synthesis.

PMID- 9618583
TI  - Developmental changes in heteroplasmy level and mitochondrial gene expression in
      a Drosophila subobscura mitochondrial deletion mutant.
AB  - Eighty percent of DNA molecules are deleted in the mitochondrial population of an
      adult mutant strain of D. subobscura. Both intact and deleted genomes are
      autonomous monomers. The heteroplasmy level, which is lower in germ tissue,
      increases from the oocytes (60%) to the third larval instar (83%), and is then
      maintained throughout the life of the fly. The mtDNA/nuclear DNA ratio is on
      average two-times greater in the heteroplasmic strain than in the wild-type
      strain, irrespective of the stage, but the cellular content of mitochondria is
      elevated only in the embryos and pupae of the mutant strain. The steady state
      concentrations (SSCs) of the transcripts affected by the deletion are greatly
      reduced at the larval and adult stages, and less so at the pupal stage of the
      mutant strain compared with the wild-type. The SSCs of these transcripts are
      identical in the two strains at the embryonic stage. The fusion transcript,
      indicating that the deleted genome is expressed, was detected at all stages. The
      mechanisms involved in the changes in the heteroplasmy level during the course of
      development and in its maintenance from the third larval instar onwards are
      discussed.

PMID- 9618584
TI  - Mapping of promoters for the nucleus-encoded plastid RNA polymerase (NEP) in the
      iojap maize mutant.
AB  - Plastid genes of higher plants may be transcribed by the plastid-encoded or the
      nucleus-encoded plastid RNA polymerases (PEP or NEP). The objective of this study
      was to identify NEP promoters in maize. To separate the NEP and PEP transcription
      activity, NEP promoter mapping was carried out in the iojap maize mutant which
      lacks the PEP. We report here that atpB, an ATPase subunit gene has promoters for
      both NEP and PEP, while clpP, a protease subunit gene, and the rpoB operon,
      encoding three PEP subunit genes, are exclusively transcribed from NEP promoters.
      The maize NEP promoters share sequence homology around the transcription
      initiation site, including the ATAGAATA/GAA loose consensus identified for
      tobacco, suggesting conservation of the NEP transcription machinery between
      monocots and dicots.

PMID- 9618585
TI  - Reciprocal translocation at duplicated RPL2 loci might cause speciation of
      Saccharomyces bayanus and Saccharomyces cerevisiae.
AB  - By a genomic comparison of two sibling yeasts, Saccharomyces bayanus and S.
      cerevisiae, we previously demonstrated that chromosomes II and IV of S.
      cerevisiae were rearranged into chromosomes 12 and 14 of S. bayanus or vice
      versa. In the present study we have delimited the translocation break sites in
      chromosomes II and IV by Southern hybridization using DNA fragments of S.
      cerevisiae cosmid clones as probes. The results suggest that the reciprocal
      translocation of chromosomes II and IV had occurred at duplicated RPL2 loci.
      Furthermore, the translocation sites in S. bayanus were confirmed by the cloning
      and sequence analysis of the regions flanking RPL2 loci. Several genes in the
      regions flanking the RPL2 loci were present in the order expected for a
      translocation at these loci between the two species. These results indicated that
      the reciprocal translocation between chromosomes II and IV was generated by
      homologous recombination at duplicated RPL2 loci on the two chromosomes.
      Therefore, we propose that duplicated genes or duplicated regions play an
      important role in altering genomic organization during the speciation of S.
      bayanus and S. cerevisiae.

PMID- 9618586
TI  - Identification of three ubiquitin genes of the rice blast fungus Magnaporthe
      grisea, one of which is highly expressed during initial stages of plant
      colonisation.
AB  - Differential cDNA screening was used to identify genes expressed during the
      colonisation of rice leaves by the pathogenic fungus Magnaporthe grisea. This led
      to the identification of a gene, called UEP1, which encodes a ubiquitin extension
      protein. UEP1 was highly expressed 48 h after initial fungal infection of rice
      leaves when M. grisea is proliferating in the leaf epidermis but not yet causing
      disease symptoms. UEP1 appeared to be down-regulated after this time despite
      further extensive growth of the fungus throughout the leaf tissue. To investigate
      the potential role of ubiquitin in fungal pathogenesis we subsequently isolated
      UEP3 and PUB4, encoding a second ubiquitin extension protein and a polyubiquitin
      respectively. UEP1 was expressed abundantly during active growth of M. grisea in
      axenic culture but was down-regulated by starvation-stress. UEP3 showed a similar
      pattern of expression to UEP1 during the growth of M. grisea in culture and after
      environmental stress, but was not highly expressed during plant colonisation.
      PUB4 was highly expressed after environmental stress, but was not highly
      expressed during plant colonisation. UEP1 was found to be present in a much
      higher copy number per haploid genome compared to UEP3 and PUB4. The restricted
      high-level expression of UEP1 suggests that M. grisea undergoes rapid ribosomal
      biogenesis and protein turnover during initial plant-tissue colonisation, which
      is regulated by a specific UEP1-encoded component of the M. grisea ubiquitin gene
      family.

PMID- 9618587
TI  - Ribosomal DNA internal transcribed spacer sequences do not support the species
      status of Ampelomyces quisqualis, a hyperparasite of powdery mildew fungi.
AB  - Phylogenetic relationships among Ampelomyces isolates, pycnidial hyperparasites
      and biological control agents of powdery mildews, were inferred from internal
      transcribed spacer (ITS) sequences of the ribosomal DNA (rDNA). Currently, these
      hyperparasites are considered to be a single species, A. quisqualis, despite
      observed morphological and cultural differences. Ten Ampelomyces isolates,
      representing seven previously defined ITS RFLP groups, were sequenced and
      analyzed. Sequence-divergence values among isolates belonging to different RFLP
      groups ranged from 4.3 to 22.4%, suggesting that these isolates may represent
      different taxa. When Ampelomyces ITS sequences were analyzed by cladistic methods
      with the sequences of other ascomycetous fungi, they formed two lineages in the
      Dothideales. Slow-growing Ampelomyces isolates formed a clade with Leptosphaeria
      microscopica and L. nodorum, whereas fast-growing Ampelomyces isolates formed a
      clade with Epicoccum nigrum. Sequence-divergence values between these two clades
      ranged from 17.3 to 22.4%, suggesting that the taxa in the two clades are not
      closely related and possibly not congeneric. The data presented here indicate
      that the identification of 'A. quisqualis' isolates used in biological control
      experiments should be re-evaluated.

PMID- 9618588
TI  - Paxilline-negative mutants of Penicillium paxilli generated by heterologous and
      homologous plasmid integration.
AB  - Using a monoclonal antibody based ELISA, 600 pAN7-1 plasmid-tagged mutants of
      Penicillium paxilli were screened for paxilline accumulation and one paxilline
      negative mutant, YI-20, was identified. A molecular analysis of this mutant
      showed that pAN7-1 was inserted at a single site but was present as 4-6 copies
      arranged in a head-to-tail tandem array. Rescue of flanking sequences and
      analysis of the corresponding genomic region revealed that YI-20 has an extensive
      deletion at the site of pAN7-1 integration. Probing of a CHEF gel with the same
      sequences showed that associated with the deletion is a rearrangement of
      chromosome Va. Targeted gene disruption of wild-type sequences adjacent to the
      site where pAN7-1 inserted, resulted in the generation of two additional
      paxilline-negative mutants; both were single crossovers with deletions extending
      outside the region mapped. Neither of these new mutants had a rearrangement of
      chromosome Va, suggesting that deletion of genes on this chromosome is
      responsible for the paxilline-negative phenotype. Telomeric fingerprinting of
      genomic digests of P. paxilli, combined with pulsed-field gel electrophoresis of
      chromosomal DNA, established that there are a minimum of eight chromosomes in
      this fungus.

PMID- 9618589
TI  - Development of a homologous transformation system for the human pathogenic fungus
      Aspergillus fumigatus based on the pyrG gene encoding orotidine 5'-monophosphate
      decarboxylase.
AB  - A homologous transformation system for the opportunistic fungal pathogen
      Aspergillus fumigatus was developed. It is based on the A. fumigatus pyrG gene,
      encoding orotidine 5'-monophosphate decarboxylase, which was cloned and
      sequenced. Transformation of both Aspergillus (Emericella) nidulans and A.
      fumigatus pyrG mutant strains by the use of protoplasts or electroporation
      established the functionality of the cloned gene. DNA sequencing of the A.
      fumigatus pyrG1 mutant allele revealed that it encodes a truncated, non
      functional, PyrG protein. Transformation of an A. fumigatus pyrG1 mutant with a
      plasmid carrying the novel pyrG2 allele constructed by in vitro mutagenesis
      yielded prototrophic transformants following recombination between both mutation
      sites. Analysis of transformants carrying the entire plasmid showed that up to
      45% of integration had occurred at the pyrG locus. This provides a tool to target
      defined genetic constructs at a specific locus in the A. fumigatus genome in
      order to study gene regulation and function.

PMID- 9618600
TI  - The threat of things biological.

PMID- 9618601
TI  - The establishment and duration of breastfeeding. Part 1: Hospital influences.
AB  - Most New Zealand mothers initiate breastfeeding in hospital, but many continue
      for only a relatively short time. Focus group discussions with mothers and health
      care workers on their perceptions of important factors influencing the duration
      of breastfeeding indicated many negative initial hospital experiences. Specific
      concerns included overworked staff; lack of health care workers' skills,
      particularly in helping infants to latch on; inconsistent advice; noise and
      embarrassment in four bedded rooms; and the impact of changes in the provision of
      maternity services and funding.

PMID- 9618602
TI  - The establishment and duration of breastfeeding. Part 2: Community influences.
AB  - Most New Zealand mothers initiate breastfeeding in hospital, but many continue
      for only a relatively short time. This paper reports on mothers' and health care
      workers' perceptions of important community factors influencing the duration of
      breastfeeding. Data collection was by focus group discussions. The results
      indicate that some mothers have specific plans regarding the duration of
      breastfeeding but many do not. The importance of practical help, realistic role
      expectations, community acceptance especially amongst men, adequate maternity
      leave, and help for those returning to work is emphasised. Conflicting opinions
      exist about the difficulties of introducing older infants to bottles.

PMID- 9618603
TI  - Breastfeeding, work and women's health among Thai women in Chiang Mai.
AB  - Reconciling the conflicting rights and demands of women's productive and
      reproductive roles poses an increasing challenge to health policy formulation.
      This article derives from a combined qualitative and quantitative study conducted
      in Chiang Mai, Thailand. It discusses situations and difficulties relevant to the
      health of employed women who breastfed their infants. Three hundred and thirteen
      employed women were interviewed to explore their experiences as mothers,
      particularly their attempts to balance the demands of work and breastfeeding. The
      findings demonstrate the stresses and conflicts in combining breastfeeding with
      work that can affect both physical and emotional health. Some women developed
      negative feelings. Exhaustion or fatigue, lack of self care and not eating
      properly were the common physical problems reported by women in this study.

PMID- 9618604
TI  - Breastfeeding information and support services offered by Melbourne hospitals in
      antenatal classes.
AB  - Breastfeeding in industrialised societies is affected by a number of factors
      including antenatal class participation, timing of breastfeeding education,
      support networks available, and fathers' opinions. This study aimed to
      investigate the availability and type of breastfeeding information and support
      services offered by Melbourne hospitals. This was discussed in regard to the
      possible effect this may have on mothers' choice of feeding method. All hospitals
      known by Nursing Mothers' Association of Australia (NMAA) to be involved in
      obstetric care were asked to complete a questionnaire. Factors such as antenatal
      class timing, attendance, cost and content were investigated as indicators of the
      extent of services available. Specifically, services and information offered for
      women from non English speaking backgrounds (NESB) and from Aboriginal and Torres
      Strait Islands were identified. The study found that breastfeeding education is a
      small part of antenatal education in Melbourne hospitals. The inclusion of NMAA
      was widespread among hospitals, allowing access to information and support
      services. The amount of information and support services available for women from
      NESB and Aboriginal and Torres Strait Islander background needs to be expanded.

PMID- 9618605
TI  - Lactose intolerance.

PMID- 9618606
TI  - Breastfeeding and the use of human milk. American Academy of Pediatrics, Work
      Group on Breastfeeding.
AB  - This policy statement on breastfeeding replaces the previous policy statement of
      the American Academy of Pediatrics, reflecting the considerable advances that
      have occurred in recent years in the scientific knowledge of the benefits of
      breastfeeding, in the mechanisms underlying these benefits, and in the practice
      of breastfeeding. This document summarizes the benefits of breastfeeding to the
      infant, the mother, and the nation, and sets forth principles to guide the
      pediatrician and other health care providers in the initiation and maintenance of
      breastfeeding. The policy statement also delineates the various ways in which
      pediatricians can promote, protect, and support breastfeeding, not only in their
      individual practices but also in the hospital, medical school, community, and
      nation.

PMID- 9618607
TI  - Endosonography of the anal sphincter muscles in healthy volunteers and in
      patients with defecation disorders.

PMID- 9618608
TI  - The era of health promotion for children and adolescents--a cross-sectional
      survey of strategies and new knowledge.

PMID- 9618609
TI  - Prevention of neonatal tetanus.

PMID- 9618610
TI  - Annotation: prevention of HIV, other sexually transmitted diseases, and unwanted
      pregnancy--testing physical barriers available to women.

PMID- 9618611
TI  - Topics for our times: managed care and public health opportunities.

PMID- 9618612
TI  - Health benefits and risks of reporting HIV-infected individuals by name.
AB  - With more treatment options emerging for human immunodeficiency virus (HIV)
      infection, the policy of reporting HIV-infected individuals by name merits
      reevaluation. This paper reviews the benefits and risks of name reporting of
      persons infected with HIV. Public health departments have linked name reporting
      with medical referrals, risk reduction counseling, and partner notification
      programs. Yet some studies indicate that people are less likely to be tested for
      HIV infection when name reporting is implemented. Whether name reporting actually
      improves individual or public health, therefore justifying the increased risk of
      loss of confidentiality and possibly reduced testing rates, remains unknown. The
      lack of health outcome data on name reporting allows beliefs rather than facts to
      dominate debate about this policy. Before this practice is more widely adopted, a
      determination should be made as to whether the potential benefits of name
      reporting outweigh the risks.

PMID- 9618613
TI  - Children in special education programs: attention deficit hyperactivity disorder,
      use of services, and unmet needs.
AB  - OBJECTIVES: Attention deficit hyperactivity disorder (ADHD), a common psychiatric
      condition, may impair a child's ability to learn and to form social
      relationships, tasks critical to healthy development. This study describes the
      prevalence of the disorder among children in special education programs and
      identifies the extent and predictors of unmet service needs. METHODS: A 2-stage
      screening protocol of a countywide population of second- through fourth-grade
      students in special education was conducted to (1) screen for ADHD, employing
      standardized parent and teacher questionnaires, and determine health services use
      (n = 499) and (2) perform diagnostic assessments of ADHD (n = 318). RESULTS:
      Almost half of the children qualified for a diagnosis of ADHD, yet only half of
      those were reportedly receiving care for the condition, mainly in the general
      health care sector. Girls were more than 3 times as likely as boys to have unmet
      service needs; minority status, low income, and health maintenance organization
      coverage also emerged as possible risk factors for unmet service needs.
      CONCLUSIONS: ADHD is a common yet often untreated condition among children in
      special education. Mental health services for children with this disorder should
      be integrated with general health care and special education programs.

PMID- 9618614
TI  - Explaining recent increases in students' marijuana use: impacts of perceived
      risks and disapproval, 1976 through 1996.
AB  - OBJECTIVES: Marijuana use among high school seniors increased during most of the
      1970s, decreased throughout the 1980s, and has been increasing again during the
      1990s. Earlier analyses of the classes of 1976 through 1986 attributed the
      historic trends during that period to specific changes in views about marijuana.
      This study examined whether recent increases in marijuana use among seniors and
      among students in earlier grades reflect similar processes. METHODS: Multivariate
      regression analyses were conducted on data from large annual nationwide surveys
      of high school seniors from 1976 through 1996 (approximate n = 61,000) and 8th
      and 10th graders from 1991 through 1996 (n's = 87,911 and 82,475, respectively).
      RESULTS: Individual lifestyle factors (grades, truancy, religious commitment,
      evenings out for recreation) correlated substantially with marijuana use but did
      not explain the historic changes in marijuana use. Rather, decreases in perceived
      risk of harmfulness and in disapproval can account for the recent increases in
      all 3 grades and for earlier decreases among seniors. CONCLUSIONS: These findings
      indicate that perceived risks and disapproval are important determinants of
      marijuana use. Accordingly, prevention efforts should include realistic
      information about risks and consequences of marijuana use.

PMID- 9618615
TI  - Exposure of young infants to environmental tobacco smoke: breast-feeding among
      smoking mothers.
AB  - OBJECTIVES: This study examined the degree to which breast-feeding and cigarette
      smoking by mothers and smoking by other household members contribute to the
      exposure of infants to the products of tobacco smoke. METHODS: The subjects were
      330 mother-infant pairs derived from a cohort of 1000 pairs enrolled in a
      longitudinal study of the pulmonary effects of prenatal and postnatal smoking.
      The main outcome measure was corrected urinary cotinine levels. RESULTS: Urinary
      cotinine levels were 10-fold higher in breast-fed infants of smoking mothers than
      among bottle-fed infants of smoking mothers. Among infants of nonsmoking mothers,
      urine cotinine levels were significantly increased in infants living in homes
      with other smokers; in this group there was no significant difference between
      bottle-fed and breast-fed infants. Infants whose mothers smoked in the same room
      as the infant had only nonsignificant increases in cotinine levels compared with
      infants whose mothers restricted their smoking to other rooms. CONCLUSIONS:
      Breast-fed infants of smoking mothers have urine cotinine levels 10-fold higher
      than bottle-fed infants whose mothers smoke, suggesting that breast-feeding,
      rather than direct inhalation of environmental tobacco smoke, is the primary
      determinant of cotinine levels in infants whose mothers smoke.

PMID- 9618616
TI  - Use of health services by children of smokers and nonsmokers in a health
      maintenance organization.
AB  - OBJECTIVES: Use of health services by children of smokers and nonsmokers was
      compared to assess whether exposure to environmental tobacco smoke resulted in
      greater use of health services among children of smokers. METHODS: Primary care
      and emergency room visits, asthma-related prescriptions, and inpatient stays over
      the 42-month study period were compared for children of smokers (n = 498) and
      nonsmokers (n = 1062) who were enrolled in a health maintenance organization.
      Parents of children aged 1 through 11 years were identified from participants in
      2 randomized smoking cessation trials. RESULTS: After adjustment for parental
      age, education, and health status and for child's age, there were no differences
      between children of smokers and children of nonsmokers in use of primary care or
      emergency room visits, asthma-related prescriptions, or inpatient stays. However,
      among those with any preventive care visits, children of smokers had
      significantly fewer visits than children of nonsmokers. CONCLUSIONS: Further
      study is needed to elucidate whether parents who smoke underutilize health
      services for their children or use services differently from nonsmoking parents
      and whether these differences have cost implications.

PMID- 9618617
TI  - Duration of protective immunity conferred by maternal tetanus toxoid
      immunization: further evidence from Matlab, Bangladesh.
AB  - OBJECTIVES: Although maternal tetanus immunization has been shown to be highly
      effective in the prevention of neonatal tetanus, unresolved questions remain
      concerning the required minimum number of doses and the resulting duration of
      effective immunity. This study examined the duration of effective immunity
      against neonatal tetanus provided by maternal tetanus immunization. METHODS: A
      randomized, double-blind cholera vaccine trial of 41,571 children and nonpregnant
      adult women carried out in 1974 in the Matlab comparison area of rural Bangladesh
      provided a unique opportunity to address dose and immunity issues. RESULTS:
      Children of women who received either 1 or 2 injections of tetanus toxoid
      experienced 4- to 14-day mortality levels consistently lower than those of
      children of unimmunized mothers. Analysis of neonatal-tetanus-related mortality
      showed that 2 injections of tetanus toxoid provided significant protection for
      subsequent durations of up to 12 or 13 years. CONCLUSIONS: The data demonstrate
      that a limited-dose regimen of maternal tetanus toxoid provides significant and
      extended protection against the risk of neonatal tetanus death.

PMID- 9618618
TI  - Utility of percentage of births to teenagers as a surrogate for the teen birth
      rate.
AB  - OBJECTIVES: The teen birth rate is commonly used in comparing regional variation
      in teen pregnancies, but local teen birth rates are not always available. In this
      study the percentage of all births that are to teens was evaluated for its
      utility as a surrogate for the teen birth rate. METHODS: Rank correlation and
      sensitivity and specificity analyses were used. RESULTS: The Spearman rank
      correlations between percentage of teen births (PTB) and teen birth rate (TBR)
      were .995, .906, and .841 for the 3 age groups suggesting that it may be
      reasonable to employ PTB to prioritize zip codes. Zip codes with upper quartile
      levels of percentages of teen births identified zip codes with upper quartile
      levels of TBR with a sensitivity of 83.8%, 68.8%, and 65%; a false-positive rate
      of 2.1%, 8.6%, and 10%; and a positive predictive value of 89.3%, 67.6%, and
      67.5% for the age groups 10 through 14, 15 through 17, and 18 through 19 years.
      CONCLUSIONS: The percentage of births to teens is a useful surrogate for teen
      birth rate in California, especially among younger teenagers.

PMID- 9618619
TI  - Coronary heart disease risk factors and attributable risks in African-American
      women and men: NHANES I epidemiologic follow-up study.
AB  - OBJECTIVES: This study assessed associations of risk factors with coronary heart
      disease incidence in African Americans. METHODS: The participants in the NHANES I
      Epidemiologic Follow-Up Study included in this analysis were 1641 Black and 9660
      White persons who were aged 25 to 74 years when examined and who did not have a
      history of coronary heart disease. Average follow-up for survivors was 19 years.
      RESULTS: Significant, independent risk factors for coronary heart disease were
      age, systolic blood pressure, and smoking in Black women and age, systolic blood
      pressure, serum cholesterol, low education, and low family income in Black men.
      In this cohort, 19% of incident coronary heart disease in Black women and 34% in
      Black men might be prevented if systolic blood pressure were below 140 mm Hg. In
      Black men, attributable risk for low education (46%) was even higher than that
      for elevated blood pressure. CONCLUSIONS: Elevated systolic blood pressure and
      smoking were predictive of coronary heart disease incidence in African Americans.
      Estimates of population attributable risk were highest for elevated systolic
      blood pressure in women and education less than high school in men. Further
      studies of serum lipids, education, and coronary heart disease in Black women are
      needed.

PMID- 9618620
TI  - Are tobacco industry campaign contributions influencing state legislative
      behavior?
AB  - OBJECTIVES: This study tested the hypothesis that tobacco industry campaign
      contributions influence state legislators' behavior. METHODS: Multivariate
      simultaneous equations regression was used to analyze data on tobacco industry
      campaign contributions to state legislators and legislators' tobacco control
      policy scores in 6 states. Campaign contributions were obtained from disclosure
      statements available in the specific state agency that gathers such information
      in each state. Tobacco policy scores were derived from a survey of key informants
      working on tobacco issues in each state. RESULTS: As tobacco industry
      contributions increase, a legislator's tobacco policy score tends to decrease
      (i.e., become more pro-tobacco industry). A more pro-tobacco position was
      associated with larger contributions from the industry. These results were
      significant even after controls for partisanship, majority party status, and
      leadership effects. In California, campaign contributions were still
      significantly related to tobacco policy scores after controls for constituent
      attitudes and legislators' personal characteristics. CONCLUSIONS: Tobacco
      industry campaign contributions influence state legislators in terms of tobacco
      control policy-making.

PMID- 9618621
TI  - Injury and anomie: effects of violence on an inner-city community.
AB  - OBJECTIVES: Widespread violence affects individuals but also alters group life.
      This study was designed to examine the effects of violence on an inner-city
      community. METHODS: A qualitative study was undertaken that included field
      observations and semistructured interviews. The study took place in Washington
      Heights, a New York City neighborhood with a high rate of violence, largely
      secondary to the drug trade. RESULTS: The 100 people interviewed differed widely
      in their definitions of violence and in their likelihood of having experienced
      violent acts in the course of daily life. High, medium, and low violence
      microenvironments were identified; risk of exposure to violence, but not
      individual definitions of violence, differed by location. Violence in all parts
      of the neighborhood inhibited social interactions, but the intensity of this
      effect differed by microenvironment. CONCLUSIONS: In Washington Heights, violence
      has injured individuals and fractured social relationships, leading to the state
      of social disarray referred to as "anomie." The public health response to the
      violence epidemic should address anomie through community organizing efforts.

PMID- 9618622
TI  - State variations in supplemental security income enrollment for children and
      adolescents.
AB  - OBJECTIVES: The purpose of this study was to determine the effects of poverty,
      program generosity, and health on state variations in enrollment of children and
      adolescents in the Supplemental Security Income (SSI) program during recent
      program expansions. METHODS: The relationship of state SSI rates for 1989 and
      1992 to child poverty, health, and program generosity were determined by multiple
      regression. RESULTS: The mean percentage of children enrolled grew from 0.36%
      (1989) to 0.75% (1992). Poverty rates accounted for 78% of the variance among
      states in 1989 and 53% in 1992. Other indicators accounted for little variance.
      CONCLUSIONS: Differences in state poverty levels explained almost all variation
      in SSI enrollment.

PMID- 9618623
TI  - Evaluation of an enforcement program to reduce tobacco sales to minors.
AB  - OBJECTIVES: This study evaluated an active enforcement program to increase
      retailers' compliance with the law prohibiting tobacco sales to minors. METHODS:
      Tobacco sales to minors were monitored in 319 outlets in 6 pairs of communities
      in Erie County, New York. One community in each pair was randomly assigned to an
      enforcement intervention. RESULTS: Retailers' compliance with the law increased
      from 35% in 1994 to 73% in 1995. However, the change in compliance rates was
      roughly the same for stores in the enforcement and nonenforcement communities.
      CONCLUSIONS: Active compliance checking of retail outlets as a strategy to reduce
      illegal tobacco sales to minors may only be necessary insofar as it contributes
      to an increase in retailers' perception that the threat of enforcement is real.

PMID- 9618624
TI  - Laying down the law: reducing illegal tobacco sales to minors in central Harlem.
AB  - OBJECTIVES: This study compared the impact of educational and enforcement
      interventions on retailers' sale of tobacco to minors in Central Harlem, New
      York. METHODS: In a randomized trial with repeated measures, 152 stores were
      randomly divided into control, education, and enforcement groups. RESULTS:
      Overall tobacco sales to 12- and 13-year-old minors at baseline (98%) were among
      the highest in the nation. At 6-month and 1-year follow-ups, decreases in rates
      of tobacco sales to minors were modest among education stores and substantial
      among enforcement stores. CONCLUSIONS: Effective reduction of tobacco sales to
      minors may require ongoing enforcement measures, including fines for retailers
      who violate state and local laws.

PMID- 9618625
TI  - Teenage smoking, attempts to quit, and school performance.
AB  - OBJECTIVES: This study examined the relationship between school performance,
      smoking, and quitting attempts among teenagers. METHODS: A logistic regression
      model was used to predict the probability of being a current smoker or a former
      smoker. Data were derived from the 1990 California Youth Tobacco Survey. RESULTS:
      Students' school performance was a key factor in predicting smoking and quitting
      attempts when other sociodemographic and family income factors were controlled.
      CONCLUSIONS: Developing academic or remedial classes designed to improve
      students' school performance may lead to a reduction in smoking rates among
      teenagers while simultaneously providing a human capital investment in their
      futures.

PMID- 9618626
TI  - Effects of a community-based prevention program on decreasing drug use in high
      risk adolescents.
AB  - OBJECTIVES: This study investigated the secondary prevention effects of a
      substance abuse primary prevention program. METHODS: Logistic regression analyses
      were conducted on 4 waves of follow-up data from sixth- and seventh-grade
      baseline users of cigarettes, alcohol, and marijuana taking part in a school
      based program in Indianapolis. RESULTS: The program demonstrated significant
      reductions in cigarette use at the initial follow-up (6 months) and alcohol use
      at the first 2 follow-ups (up to 1.5 years). Models considering repeated measures
      also showed effects on all 3 substances. CONCLUSIONS: Primary prevention programs
      are able to reach and influence high-risk adolescents in a nonstigmatizing
      manner.

PMID- 9618628
TI  - Adolescents engaging in unhealthy weight control behaviors: are they at risk for
      other health-compromising behaviors?
AB  - OBJECTIVES: This study sought to determine whether adolescents engaging in weight
      control behaviors are at increased risk for tobacco, alcohol, and marijuana use;
      suicide ideation and attempts; and unprotected sexual activity. METHODS: Data
      were collected on a nationally representative sample of 16,296 adolescents taking
      part in the 1993 Youth Risk Behavior Survey. RESULTS: Adolescents using extreme
      weight control behaviors were at increased risk for health-compromising
      behaviors, while associations with other weight control behaviors were weak and
      inconsistent. CONCLUSIONS: The findings have relevance to clinical work with
      youth, provide a better understanding of disordered eating, and open up a number
      of opportunities for future research.

PMID- 9618627
TI  - Effects of school-based aerobic exercise on blood pressure in adolescent girls at
      risk for hypertension.
AB  - OBJECTIVES: This study evaluated the effects of aerobic exercise physical
      education on blood pressure in high-risk, predominantly African-American,
      adolescent girls. METHODS: Ninth-grade girls (n = 99) with blood pressure above
      the 67th percentile were randomized to 1 semester of aerobic exercise classes or
      standard physical education classes. RESULT: The study was completed by 88 girls.
      At posttest, only members of the aerobic exercise group increased their estimated
      cardiorespiratory fitness. The aerobic exercise group had a greater decrease in
      systolic blood pressure than the standard physical education group (P < .03).
      CONCLUSIONS: Aerobic exercise physical education is a feasible and effective
      health promotion strategy for high-risk adolescent girls.

PMID- 9618629
TI  - Changes in sexual behavior and condom use among teenaged males: 1988 to 1995.
AB  - OBJECTIVES: This study examines shifts in sexual experience and condom use among
      US teenaged males. METHODS: Results from the 1988 and 1995 National Surveys of
      Adolescent Males were compared. RESULTS: The proportion of never-married 15- to
      19-year-old males who had had sex with a female declined from 60% to 55% (P =
      .06). The share of those sexually active using a condom at last intercourse rose
      from 57% to 67% (P < .01). Overall, the proportion of males who had sex without
      condoms last year declined from 37% to 27% (P < .001). CONCLUSIONS: Although
      protective behaviors among teenagers have increased, significant proportions of
      teenagers--especially Black and Hispanic males--remain unprotected.

PMID- 9618630
TI  - Prospective psychosocial, interpersonal, and behavioral predictors of handgun
      carrying among adolescents.
AB  - OBJECTIVES: This study identified behavioral and psychosocial/interpersonal
      factors in young adolescence that are associated with handgun carrying in later
      adolescence. METHODS: A sample of 2200 high school students was surveyed at 9th
      grade and again at 12th grade. RESULTS: Multivariate logistic regression analyses
      indicated that measures of risk-taking preference, depression, stress, temper,
      and drug use assessed while the students were in 9th grade were predictive of
      handgun carrying in 12th grade for both male and female students. CONCLUSIONS:
      These findings suggest the need for a comprehensive approach to prevention that
      focuses on both individual and interpersonal factors associated with adolescents'
      decision to carry a handgun.

PMID- 9618631
TI  - Association between duration of residence and access to ambulatory care among
      Caribbean immigrant adolescents.
AB  - OBJECTIVES: The purpose of this study was to determine the association between
      duration of residence and access to ambulatory care among Caribbean immigrant
      adolescents. METHODS: A cross-sectional survey of adolescents at a New York City
      high school was conducted. Multivariate modeling methods were used to adjust for
      demographic and socioeconomic covariates. RESULTS: Duration of residence was
      strongly and directly associated with access to ambulatory care after adjustment
      for ethnicity. CONCLUSIONS: Caribbean immigrant adolescents, particularly recent
      immigrants, have reduced access to ambulatory care.

PMID- 9618632
TI  - Immigration reporting laws: ethical dilemmas in pediatric practice.
AB  - Objectives. This study assessed the potential impact of immigration reporting
      requirements on pediatricians' referrals to child protective services.Methods.A
      random sample of 200 Massachusetts pediatricians were surveyed. Chi-square and
      logistic regression analyses were performed.Results.Asked whether potential
      deportation of the family would cause them to question or alter a decision to
      refer, 50% of the respondents said yes.Conclusions.Pediatricians, as mandated
      reporters of child abuse, will face ethical dilemmas if laws requiring reporting
      of immigration status are enacted. (Am J Public Health. 1998;88:967-968)

PMID- 9618633
TI  - State estimates of household exposure to firearms, loaded firearms, and handguns,
      1991 through 1995.
AB  - OBJECTIVES: Variations among states in household exposure to firearms, loaded
      firearms, and handguns were examined. METHODS: Data from the Behavioral Risk
      Factor Surveillance System in 22 states were used to estimate the prevalence of
      adults and children exposed to household firearms. RESULTS: The prevalence of
      adults living in households with firearms ranged from 12% to 57%; the
      corresponding ranges were 1% to 23% for loaded firearms and 5% to 36% for
      handguns. The prevalence of children less than 18 years of age living in
      households with loaded firearms ranged from 2% to 12%. CONCLUSIONS: Important
      variations among states exist in the prevalence of adults and children living in
      households with firearms, loaded firearms, and handguns.

PMID- 9618635
TI  - Neighbor to neighbor: working together for healthy families through an urban
      community partnership.

PMID- 9618634
TI  - Phantom of the area: poverty-area residence and mortality in the United States.
AB  - OBJECTIVES: The purpose of the study was to conduct a national multivariate
      analysis on poverty-area residence and mortality in the United States. METHODS:
      Proportional hazards analyses were performed of the effect of poverty-area
      residence on the risk of mortality among adult examinees in the 1971 through 1974
      National Health and Nutrition Examination Survey who were followed through 1987.
      RESULTS: Poverty-area residence was associated with significantly elevated risk
      of all-cause mortality (rate ratio = 1.78, 95% confidence interval = 1.33, 2.38)
      and some cause-specific mortality among those aged 25 through 54 years, but not
      among those aged 55 through 74 years, at baseline after adjustment for several
      individual and household characteristics. CONCLUSIONS: Residence in poverty areas
      contributes to socioeconomic gradients in mortality among nonelderly adults in
      the United States.

PMID- 9618636
TI  - Project HAPPEN: where law enforcement and housing code enforcement meet.

PMID- 9618637
TI  - Do shall-issue laws save lives?

PMID- 9618639
TI  - [Axillary node removal in clinical node-negative breast carcinoma. Can its
      indication be individualized by "sentinel node" detection?].
AB  - BACKGROUND AND OBJECTIVE: The status of the axillary lymph node(s) is an
      important prognostic factor in breast cancer and thus decisive in the indication
      for adjuvant treatment. This study investigated the extent to which examination
      of the sentinel node (SN) can individualize the need for axillary resection and
      the diagnosis of lymph nodes be optimized. PATIENTS AND METHODS: 96 consecutive
      patients with breast cancer were studied (94 women, 2 men; mean age 59 [36-84]
      years) in whom no lymph node enlargement had been diagnosed clinically. After
      preoperative lymph-drainage scintigraphy with 99mTc Nanocoll combined with
      intraoperative scintillation probe detection the SN node was identified in 77 of
      the 96 patients and was removed. Subsequently the axillary lymph nodes in level I
      and II were removed by a standard technique and all removed lymph nodes and
      material then compared histologically. RESULTS: In nine of 77 patients with
      identifiable SN it was the only lymph node with metastasis. In 18 patients both
      the SN and other axillary lymph nodes were infiltrated. The SN and other axillary
      lymph nodes were free of metastases in 44 patients. In six patients the SN was
      not representative, since it was free of tumour, but other axillary nodes were
      not. Identification of a SN and prognostication of lymphogenic axillary
      metastases depended on tumour size. Among T3 and T4 tumours, ten of 16 had a
      verifiable SN, but in six of them it was not representative for axillary
      metastasization. But in 62 of 73 patients with tumours up to 5 cm in diameter
      without involvement of skin or chest wall (T1 and T2, respectively) a SN could be
      identified that was not representative for axillary metastases in only two cases.
      CONCLUSIONS: SN resection in breast cancer makes it possible to individualize
      axillary node resection as part of primary treatment. Specific histological
      examination of serial sections and immunohistological testing may possibly
      increase the accuracy of histological diagnosis.

PMID- 9618640
TI  - [Puerperal sepsis caused by streptococcus group A with a severe form of
      progression like "toxic shock-like syndrome"].
AB  - HISTORY AND CLINICAL FINDINGS: A previously healthy 32-year-old woman was
      admitted with shock symptoms 5 days after an uneventful home delivery. She
      developed a fever up to 39.5 degrees C during the days after delivery with sore
      throat, diarrhoea and muscle aches in all limbs. On physical examination there
      were swellings of the arms and lower legs as well as macular and vesicular
      erythrodermia, especially of the trunk. INVESTIGATIONS: Abnormal laboratory
      findings were thrombocytopenia (20,000/microliters), increased serum
      concentrations of fibrin breakdown products (102 mg/dl) and of C-reactive protein
      (> 200 mg/dl), increased creatine kinase (5700 U/l), transaminases (GOT 220 U/l,
      GPT 52 U/l), creatinine (2.0 mg/dl) and urea (114 mg/dl). Streptococcus pyogenes
      was grown on blood culture and from vaginal smear. Sonography, echocardiography
      and radiological examinations failed to demonstrate a septic focus. TREATMENT AND
      COURSE: Mechanical ventilation was required for 7 days because of respiratory
      failure and shock symptoms (toxic shock-like syndrome, TSLS). Penicillin G and
      tobramycin were given after the bacteriological diagnosis. Severe consumption
      coagulopathy was successfully treated with antithrombin III and platelet
      concentrates. After extubation she was found to have a flaccid tetraparesis,
      especially of the right and of the legs, due to soft-tissue necrosis and damage
      to peripheral nerves. An embolic occlusion of the right brachial artery 4 weeks
      after onset of the disease required upper-arm amputation. CONCLUSION: One of the
      decisive factors for the prognosis of TSLS is early antibiotic treatment. The
      prodromal symptoms in this case underline the necessity of early recognition and
      treatment to prevent a full-blown picture of the syndrome.

PMID- 9618641
TI  - [Neurologic cause for a respiratory insufficiency].
AB  - HISTORY AND CLINICAL FINDING: A 73-year-old man developed progressive respiratory
      failure within 24 hours, requiring emergency admission for mechanical
      ventilation. The cause of the dyspnoea and tachypnoea could not be ascertained by
      routine medical and neurological examination. Neuromuscular disease or a cerebral
      lesion was considered in the differential diagnosis, together with a
      cardiovascular cause. INVESTIGATIONS: Neither laboratory tests nor additional
      investigations (chest radiogram, echocardiography) gave a diagnosis. Magnetic
      resonance imaging and computed tomography excluded a focal cerebral or spinal
      lesion or a space-occupying lesion in the region of the phrenic nerve. An
      electrophysiological tests (EPT) failed to establish a neuromuscular disease.
      However, when signs of upper motor neurone irritation appeared, more detailed
      EPTs, also of the muscles of breathing, provided the diagnosis of amyotrophic
      lateral sclerosis (ALS). TREATMENT AND COURSE: Symptomatic treatment with
      pyridostigmine made it possible gradually to wean the patients off the ventilator
      so that he could be sent home on intermittent mechanical ventilation. CONCLUSION:
      In case of acute respiratory failure without cardiopulmonary cause motoneurone
      disease with initial involvement of respiratory musculature should be considered,
      even in the absence of clinical signs, and special electrophysiological tests may
      be necessary to recognize the underlying disease.

PMID- 9618642
TI  - [Tachycardia heart rhythm disorders after aortocoronary bypass surgery].

PMID- 9618643
TI  - [Low molecular weight heparin in venous thromboembolism. Mechanism of action,
      therapy and prophylaxis].

PMID- 9618644
TI  - [Subsequent approval as a contract physician after the retirement of a doctor
      from a community practice in the restricted district. Decision of the regional
      public court in Rhineland-Pfalz of August 21, 1997].

PMID- 9618645
TI  - [Complication of percutaneous enteral gastrostomy].

PMID- 9618646
TI  - Salmonella spray promises no harm, no (infected) fowl.

PMID- 9618647
TI  - Cryptopatches: intestinal sites for gamma sigma T-cell replication.

PMID- 9618648
TI  - Nocistatin: new type of opioid?

PMID- 9618649
TI  - Image of the month. Pseudomembranous colitis.

PMID- 9618650
TI  - Oral contraceptive use and smoking are risk factors for relapse in Crohn's
      disease. The Canadian Mesalamine for Remission of Crohn's Disease Study Group.
AB  - BACKGROUND & AIMS: Lifestyle factors have been shown to influence prognosis in
      Crohn's disease. The purpose of this study was to prospectively assess the
      effects of smoking and oral contraceptive use on clinical relapse rates. METHODS:
      Placebo-treated patients formed a prospective cohort, followed up for 48 weeks or
      until relapse. The influence of smoking and the use of oral contraceptives on
      relapse risk was examined by life-table analysis (log rank tests) and Cox
      proportional hazards modeling, taking into account demographic and disease
      characteristics. RESULTS: Of 152 patients, 61 (40%) had a relapse. Univariate
      analysis showed unfavorable outcomes for women (P = 0.05), current smokers (P =
      0.005), and use of oral contraceptives (P = 0.001). Recent surgery was associated
      with a decreased risk of relapse (P = 0.02). The Cox model retained current
      smoking vs. never smoking (hazard ratio, 2.1; 95% confidence interval, 1.1-4.2),
      oral contraceptive use (hazard ratio, 3.0; 95% confidence interval, 1.5-5.9), and
      medical compared with surgical induction of remission (hazard ratio, 2.1; 95%
      confidence interval, 1.0-4.2) as predictors of relapse. Ex-smokers did not have
      an increased risk. Finally, sex, age, time in remission, disease location, and
      disease duration were not significant predictors. CONCLUSIONS: Oral contraceptive
      use and smoking are associated with an increased risk of relapse in patients with
      Crohn's disease.

PMID- 9618651
TI  - Molecular prognostic markers and colorectal cancer: the search goes on.

PMID- 9618652
TI  - Noninvasive detection of colorectal cancer by molecular tools: coming of age.

PMID- 9618653
TI  - Intestinal cell growth control: role of Src tyrosine kinases.

PMID- 9618654
TI  - A significant step in the celiac puzzle.

PMID- 9618655
TI  - The American Cancer Society guidelines for colorectal cancer screening: have we
      gone too far (or not far enough)?

PMID- 9618656
TI  - Paneth cells: on the front line or in the backfield?

PMID- 9618657
TI  - Small bowel barium studies in Crohn's disease.

PMID- 9618658
TI  - Enteroclysis or small bowel follow-through in Crohn' s diseases?

PMID- 9618659
TI  - Etiology of fasting hyperbilirubinemia.

PMID- 9618660
TI  - Deranged CD95 system in a case of Churg-Strauss vasculitis.

PMID- 9618661
TI  - Attention and distraction in pain experiments.

PMID- 9618662
TI  - Gastric maltoma with M proteins in serum and gastric juice.

PMID- 9618663
TI  - Recurrent familial cholestasis disclosed by pregnancy.

PMID- 9618664
TI  - Repaglinide for type 2 diabetes mellitus.

PMID- 9618665
TI  - Fenoldopam--a new drug for parenteral treatment of severe hypertension.

PMID- 9618666
TI  - Medicaid-dependent hospitals and their patients: how have they fared?
AB  - OBJECTIVE: To examine how private hospitals dependent on Medicaid for a large
      proportion of their revenues have fared in the face of substantial Medicaid (and
      more modest Medicare) reimbursement cutbacks and growing managed care. We
      specifically test three hypotheses regarding Medicaid-dependent hospitals: (1)
      that they are more likely to "cost-shift" cutbacks to private patients; (2) that
      they are more likely to cut services for Medicaid (and other) patients; and (3)
      that they are more likely to close. DATA/STUDY SETTING: Private short-term
      hospitals in California a state that has experienced a rapid growth in managed
      care since the early 1980s. Data are drawn from the California Office of
      Statewide Health Planning and Development (OSHPD) Hospital Disclosure Files for
      fiscal years 1983 and 1992. STUDY DESIGN: We compare changes in net prices and
      the provision of services, proxied by list price-adjusted charges, at hospitals
      for Medicaid, Medicare, and privately insured patients between fiscal years 1983
      and 1992 controlling for hospital and market characteristics, case mix, and the
      proportion of revenues from Medicaid patients. We also examine the probability
      that a hospital closed during the study period as a function of hospital and
      market characteristics and payer mix. Although the growth of managed care is
      hypothesized to reduce opportunities for "cost shifting," it may also confound
      our analysis of price changes if Medicaid-dependent hospitals are unattractive to
      managed care patients and respond by offering lower prices to plans. PRINCIPAL
      FINDINGS: We find no evidence that Medicaid-dependent hospitals raised prices to
      private patients in response to Medicaid (or Medicare) cutbacks; if anything,
      they lowered them. However, we find that service levels fell for Medicaid (and
      Medicare) patients relative to those for privately insured patients and that
      reductions were greater at Medicaid-dependent hospitals. In addition, our
      findings suggest that service levels also fell for private patients at Medicaid
      dependent hospitals, although reductions were smaller for these patients,
      suggesting that quality, may be a public good at hospitals. Finally, Medicaid
      dependent hospitals were more likely to close. CONCLUSIONS: It been suggested
      that private hospitals may respond to public reimbursement cutbacks by simply
      "shifting" costs to privately insured patients, limiting overall cost savings but
      insulating public patients and hospitals from the effects of cutbacks. We find no
      evidence of cost shifting. Rather, our results suggest that patients and
      hospitals bore the brunt of cutbacks; service levels fell at Medicaid-dependent
      hospitals and such hospitals were more likely to go out of business. This
      suggests that the consequences of proposed Medicare and Medicaid cutbacks could
      be severe for public patients and the hospitals that care for them.

PMID- 9618667
TI  - Factors important in the purchase of partnership long-term care insurance.
AB  - OBJECTIVE: To understand the factors important in the purchase of long-term care
      insurance through the Robert Wood Johnson Foundation Partnership for Long-Term
      Care. DATA SOURCES: Information on the Partnership programs, telephone surveys,
      data on Partnership purchasers, and random sample frames. STUDY DESIGN: Logistic
      regression analysis is used to examine characteristics associated with the
      purchase of a Partnership insurance policy. Independent variables are health
      status, demographic and financial characteristics, knowledge, and attitudes. DATA
      COLLECTION: A telephone survey of Partnership purchasers and a random sample of
      the population in each Partnership state were conducted. Survey questions
      included health status, opinions about long-term care and long-term care
      insurance, financial planning, demographic characteristics, and income and
      assets. PRINCIPAL FINDINGS: Important in the purchase of a Partnership policy
      were variables associated with education and knowledge about long-term care.
      Other important factors include attitudes and health status. Partnership purchase
      is associated with higher income and asset levels up to a point, with the effect
      plateauing and decreasing at the highest income and asset levels. CONCLUSIONS:
      Improved education and knowledge are important in increasing long-term care
      insurance purchase. Attitudes about having a caregiver, and about the
      government's role in paying for long-term care as well as the potential
      purchaser's willingness to consider nursing home care affect policy purchase.
      Also associated with Partnership policy purchase are better health and middle
      income and asset levels.

PMID- 9618668
TI  - The effects of New York state's ban on multiple listing for cadaveric kidney
      transplantation.
AB  - OBJECTIVE: To study the effectiveness of a 1990 ban by New York state on entry to
      more than one waiting list for a cadaver kidney transplant, and the impact of the
      ban on equity in access to transplantation. DATA SOURCES: (1) Waiting list files
      from the Organ Procurement and Transplantation Network, (2) the Health Care
      Financing Administration's Medicare Program Management and Medical Information
      System, and (3) U.S. Census Public Use Files. STUDY DESIGN: Multivariate hazard
      models were used to estimate the impact of the ban of the overall odds of
      multiple listing and on the odds of multiple listing at in-state and out-of-state
      transplant centers. After estimating the relationship between multiple listing
      and subsequent transplantation, we used simulation techniques to estimate the
      effects of a complete multiple listing ban on group waiting time differentials.
      Independent variables included demographic/socioeconomic characteristics,
      measures of ESRD severity, general transplantation suitability, measures that
      affect the likelihood of finding a good donor organ, and measures of the
      productivity of the transplant/dialysis center. PRINCIPAL FINDINGS: The ban was
      associated with a 66 percent reduction in the rate of multiple listing for New
      York patients, and multiple listing at in-state transplant centers declined by 87
      percent. Simulation results suggested that even a completely effective ban would
      produce only small, mixed equity effects. CONCLUSIONS: While the ban was
      effective in reducing the proportion of patients who registered at multiple
      transplant centers, taken together the results suggest that banning multiple
      listing is not likely to result in large improvements in equity in access to
      transplantation.

PMID- 9618669
TI  - Purchasing population health: aligning financial incentives to improve health
      outcomes.
AB  - OBJECTIVE: To review the concept of population health, including its definition,
      measurement, and determinants, and to suggest an approach for aligning financial
      incentives toward this goal. DATA SOURCE, STUDY DESIGN, DATA EXTRACTION.
      Literature review, policy analysis PRINCIPAL FINDINGS: The article presents the
      argument that a major reason for our slow progress toward health outcome
      improvement is that there is no operational definition of population health and
      that financial incentives are not aligned to this goal. Current attempts at
      process measures as indicators of quality or outcome are not adequate for the
      task. It is suggested that some measure of health-adjusted life expectancy be
      adopted for this purpose, and that integrated delivery systems and other agents
      responsible for nonmedical determinants be rewarded for improvement in this
      measure. This will require the development of an investment portfolio across the
      determinants of health based on relative marginal return to health, with
      horizontal integration strategies across sectoral boundaries. A 20-year three
      phase development strategy is proposed, including components of research and
      acceptance, integrated health system implementation, and cross-sectoral
      integration. CONCLUSIONS: The U.S. healthcare system is a $1 trillion industry
      without a definition of its product. Until population outcome measures are
      developed and rewarded for, we will not solve the twenty-first century challenge
      of maximizing health outcome improvement for the resources available.

PMID- 9618670
TI  - Use of community versus individual socioeconomic data in predicting variation in
      hospital use.
AB  - OBJECTIVES: (1) To examine the association of socioeconomic characteristics (SES)
      with hospitalization by age group, and when using measures of SES at the
      community as opposed to the individual level. (2) Thus, to support the inference
      that socioeconomic factors are important in the analysis of small area
      utilization data and address potential criticisms of this conclusion. DATA
      SOURCES: The 1989 Michigan Inpatient Database (MIDB), the 1990 U.S. Census, the
      1989 Area Resource File (ARF), and the 1990 National Health Interview Survey
      (NHIS). STUDY DESIGN: A qualitative comparison of socioeconomic predictors of
      hospitalization in two cross-sectional analyses when using community as opposed
      to individual socioeconomic characteristics was done. DATA EXTRACTION.
      Hospitalizations (excluding delivery) were extracted by county from the MIDB and
      by individual from the NHIS. SES variables were extracted from the U.S. Census
      for communities and from the NHIS for individuals. Measures of employment for
      communities were from the ARF and information on health insurance and health
      status of individuals from the NHIS. PRINCIPAL FINDINGS: Both analyses show
      similar age-specific patterns for income and education. The effects were greatest
      in young adults, and diminished with increasing age. Accounting for multiple
      admissions did not change these conclusions. In the individual-level data the
      addition of variables representing health and insurance status substantially
      diminished the size of the coefficients for the socioeconomic variables.
      CONCLUSIONS: By comparison to parallel individual-level analyses, small area
      analyses with community-level SES characteristics appear to represent the effect
      of individual-level characteristics. They are also not substantially affected by
      the inability to track individuals with multiple readmissions across hospitals.
      We conclude that the impact of SES characteristics on hospitalization rates is
      consistent when measured by individual or community-level measures and varies
      substantially by age. These variables should be included in analyses of small
      area variation.

PMID- 9618672
TI  - Psychological distress and use of ambulatory medical services in the Quebec
      Medicare system.
AB  - OBJECTIVE: To document the impact of psychological distress symptoms on the use
      of ambulatory medical services in a universal insurance coverage context. DATA
      SOURCES: Data from the Quebec Health Survey (1987) linked with billing data from
      the Quebec Medicare system. The time frame for the utilization variables is one
      year before and one year after the QHS survey. STUDY DESIGN: LISREL was used to
      test a model introducing perceived health need as an explanatory factor of the
      relationship between psychological distress and the number of visits to a
      physician. Two samples were formed from the matched file. Sample A (n = 2,000)
      was used in an exploratory phase to adequately specify the model. Sample B (n =
      2,000) was used to confirm the results obtained with Sample A. PRINCIPAL
      FINDINGS: The proposed model explained 35 percent of the number of visits to a
      physician in Sample A and 24 percent in Sample B. The effect of psychological
      distress symptoms on the respondent's perceived health need was as important as
      the effect of physical health status. The effect of the respondent's previous
      health services utilization on the number of visits to a physician was also
      significant. CONCLUSIONS: These results may be interpreted to indicate that in a
      universal insurance coverage context, psychological distress is a significant
      predictor of perceived health need.

PMID- 9618671
TI  - Resource dependence and institutional elements in nursing home TQM adoption.
AB  - OBJECTIVE: To examine the contextual attributes that influence nursing home TQM
      adoption, as informed by resource dependence and institutional theories. DATA
      SOURCES: A survey of licensed nursing home administrators in the Commonwealth of
      Pennsylvania during 1994-1995, the Medicare and Medicaid Annual Certification
      Survey (MMACS) data file, and the Area Resource File (ARF). STUDY DESIGN: Because
      the dependent variable (TQM adoption vs. non-adoption) is dichotomous, the model
      was estimated using logistic regression. DATA COLLECTION: Of the 615 facilities
      that were mailed surveys, 241 (39.2%) returned completed questionnaires. No
      significant differences were observed between respondents and nonrespondents in
      size, for-profit status, system membership, registered nurse staffing, cited
      licensure deficiencies, Medicare census, or Medicaid census. PRINCIPAL FINDINGS:
      Perceived competition, Medicare's share of total hospital discharges in the
      market, and facility Medicare census were significant predictors of TQM adoption.
      CONCLUSIONS: Our results provide limited support for the association between some
      rational adaptive and institutional factors and TQM adoption in nursing homes.
      Perceived competition and the influence of the Medicare program both at the
      facility and the market level are associated with TQM adoption. However, other
      factors associated with TQM adoption in other industries, such as size, are not
      associated with TQM adoption in the nursing homes in this study.

PMID- 9618673
TI  - Aging and primary care: an overview of organizational and behavioral issues in
      the delivery of healthcare services to older Americans.
AB  - An overview of (1) key trends shaping the healthcare environment and market; (2)
      ways in which these environmental trends are reflected in changes in the
      organization and delivery of healthcare; (3) the implications of environmental
      and organizational changes for older Americans; and (4) the research issues that
      can be addressed using organizational and behavioral theories. This introductory
      article sets the healthcare scene for the articles that follow.

PMID- 9618674
TI  - Managed care and the delivery of primary care to the elderly and the chronically
      ill.
AB  - OBJECTIVE: To analyze primary care staffing in HMOs and to review the literature
      on primary care organization and performance in managed care organizations, with
      an emphasis on the delivery of primary care to the elderly and chronically ill.
      DATA SOURCES/STUDY SETTING: Analysis of primary care staffing: InterStudy HMO
      census data on primary care (n = 1,956) and specialist (n = 1,777) physician
      staffing levels from 1991 through 1995. Primary care organization and performance
      for the chronically ill and elderly were analyzed using a review of published
      research. STUDY DESIGN: For the staffing-level models, the number of primary care
      and specialist physicians per 100,000 enrollees was regressed on HMO
      characteristics (HMO type [group, staff, network, mixed], HMO enrollment, federal
      qualification, profit status, national affiliation) and community characteristics
      (per capita income, population density, service area size, HMO competition). For
      the review of organization and performance, literature published was summarized
      in a tabular format. PRINCIPAL FINDINGS: The analysis of physician staffing shows
      that group and staff HMOs have fewer primary care and specialist physicians per
      100,000 enrollees than do network and mixed HMOs, which have fewer than IPAs.
      Larger HMOs use fewer physicians per 100,000 enrollees than smaller HMOs.
      Federally qualified HMOs have fewer primary care and specialist physicians per
      100,000 enrollees. For-profit, nationally affiliated, and Blue Cross HMOs have
      more primary care and specialist physicians than do local HMOs. HMOs in areas
      with high per capita income have more PCPs per 100,000 and a greater proportion
      of PCPs in the panel. HMO penetration decreases the use of specialists, but the
      number of HMOs increases the use of primary care and specialist physicians in
      highly competitive markets. Under very competitive conditions, HMOs appear to
      compete by increasing access to both PCPs and specialists, with a greater
      emphasis on access to specialists. The review of research on HMO performance
      suggests that access to PCPs is better in MCOs. But access to specialists and
      hospitals is lower and more difficult in MCOs than FFS. Data do not suggest that
      processes of care, given access, are different in MCOs and FFS. MCO enrollees are
      more satisfied with financial aspects of a health plan and less satisfied with
      other aspects of health plan organization. There are potential problems with
      outcomes, with some studies finding greater declines among the chronically ill in
      MCOs than FFS. We found a variety of innovative care programs for the elderly,
      based on two fundamentally different approaches: organization around primary care
      or organizing around specialty care. Differences between the performance of the
      two approaches cannot be evaluated because of the small amount of research done.
      It is difficult to say how well particular programs perform and if they can be
      replicated. The innovative programs described in the literature tend to be
      benchmark programs developed by HMOs with a strong positive reputation.

PMID- 9618676
TI  - Interorganizational factors affecting the delivery of primary care to older
      Americans.
AB  - OBJECTIVE: To discuss different types and forms of interorganizational linkages
      involved in the provision of primary care to older Americans, along with their
      distinguishing characteristics. RESEARCH STRATEGY: To take advantage of these
      linkage characteristics. The strategy requires a partnership with health services
      organizations and providers actually involved in the provision of services along
      with a planned sequence of activities involving hypotheses and methods
      development, intervention trials, and finally, demonstration and implementation.
      CONCLUSION: Because older Americans are frequent users of health services, their
      need for continuity and access provides an opportunity to examine changes to the
      delivery system and to monitor the system's capability for meeting their
      healthcare needs.

PMID- 9618675
TI  - Organizational structure and the delivery of primary care to older Americans.
AB  - OBJECTIVE: To explore how internal factors, such as organizational size, mission,
      ownership, and managerial communication and control structures, affect the
      delivery of primary care to older Americans across a wide variety of practice
      settings: ambulatory practices, hospitals, nursing homes, and home healthcare
      agencies. DESIGN: Use of the structure/process/outcome paradigm and contingency
      theory to examine the empirical research linking structural factors to outcomes.
      CONCLUSION: Using these studies as a background, we consider the implications for
      the provision of primary care to older Americans including the impact of evolving
      intraorganizational structure in healthcare organization.

PMID- 9618678
TI  - Key challenges in studying organizational issues in the delivery of healthcare to
      older Americans.
AB  - OBJECTIVE: Drawing from the articles presented in this special issue, to provide
      an overview of three key challenges facing researchers in the area of
      organizational issues in primary care delivery to older adults. CONCLUSIONS: To
      improve the quality of research done in this area we would recommend that
      researchers attend to the complexity of (1) defining an appropriate unit of
      analysis; (2) reframing our traditional models of service delivery to reflect
      ongoing changes in healthcare system actors and boundaries; and (3)
      reconceptualizing the outcomes of care to reflect adequately the reality of care
      for the aging patient.

PMID- 9618677
TI  - The emerging role of the client in the delivery of primary care to older
      Americans.
AB  - OBJECTIVE: To address the likely influences, on options faced by older clients,
      of specific changes in the delivery system and several possible responses to
      these changes and the changed options, by older persons in the aggregate. STUDY
      DESIGN: Four specific topics are discussed at length: (1) the probable altered
      role for the older healthcare client brought on by organizational changes; (2)
      findings from research on elderly health maintenance behavior and reasons for the
      increased importance of this issue; (3) the effectiveness of the conventional
      approach to explaining health services utilization in population studies; and (4)
      recommendations for future research into the direct or indirect influence of
      organizational changes in the primary healthcare system on the health-related
      decisions and behaviors of older persons.

PMID- 9618679
TI  - Expert system support using Bayesian belief networks in the prognosis of head
      injured patients of the ICU.
AB  - The present study concerns the construction and operation of a Bayesian
      analytical system, namely a Bayesian belief network (BBN) for the prognosis at 24
      h of head-injured patients of the intensive care unit. The construction of a BBN
      incorporates the maintenance of a large database including all the critical
      variables corresponding to the specific clinical domain. This database is
      processed to provide the necessary libraries of conditional probability values.
      BBNs permit the combination of prognostic evidence in a cumulative manner and
      provide a quantitative measure of certainty in the final decision. The user views
      the changes at each step, thus being capable of deciding upon the necessary
      pieces of information in order to reach a certain belief threshold. The system
      produces results that are compatible with the opinions of medical experts
      regarding the prognosis of patients exhibiting certain patterns of clinical or
      laboratory data.

PMID- 9618680
TI  - Development and trial operation of a World Wide Web-based data entry system for
      the collection of statistical data on the management of the national university
      hospitals in Japan.
AB  - A WWW-based, on-line, data-entry system for the collection of statistical data on
      the management of Japanese national university hospitals has been developed.
      Trial operation of the system showed that it can reduce the labour and budgetary
      costs of data collection and also demonstrated that an on-line, data-entry system
      is feasible in Japan. In April 1997, we began production use of the system, and
      we are to develop another WWW-based data-entry system that can deal with all
      other statistics on hospital management.

PMID- 9618681
TI  - Development and utilization of a drug information system in the Japanese
      pharmaceutical industry.
AB  - Pharmaceutical companies are responsible for providing updated, relevant
      information on the efficacy, safety and quality of drugs to medical professionals
      and finally to patients. To fulfill this responsibility, we must always endeavour
      to collect and evaluate the relevant information. We developed a drug information
      database system called Advanced Medical Online Network of Daiichi (AMOND) to
      manage various information generated during development of new products and after
      launch of the products using the classification format for retrieval. This system
      has been used for 9 years for the purpose of supporting medical representatives
      who play a primary role in the drug information services in the pharmaceutical
      industry. This system is incorporated into an on-line network system, and can be
      directly accessed by more than 1200 people at 11 branch offices and more than 110
      subbranches all over the country. We upgraded this system to AMOND-II to improve
      the function, including retrieval and output abilities. As a result, utilization
      by users of this system increased six times. We report on the improved system,
      AMOND-II and our experience of the system.

PMID- 9618682
TI  - Organizing medical networked information (OMNI).
AB  - The Internet has become a major source of biomedical information over the last 5
      years. Several projects have recently been established to help users find
      respectable information sources quickly. OMNI (Organizing Medical Networked
      Information) is one such filtering and indexing project. OMNI has focused on the
      quality of information and the application to Internet resources of standard
      tools for organizing information such as the National Library of Medicine's
      Medical Subject Headings and the Dublin Core metadata format. Now two years old,
      the OMNI project fulfils a valuable role for the UK biomedical community, through
      its gateway service (http:@omni.ac.uk), its printed resource guides and its
      training workshop programme. OMNI is also a focus for biomedical metadata
      activities in the UK. The gateway continues to grow in size and further work on
      information quality issues and integration is planned.

PMID- 9618683
TI  - Utilization of a paediatric link collection by health professionals and
      laypersons.
AB  - The Internet is an evolving resource for health-care information. However little
      information exists on providers' and other web patrons' usage of the 'medical'
      Internet. This study aims to characterize the users of a large paediatric link
      collection, describe their objectives and track their use of the information
      provided by the site. We utilized a paediatric link collection called the
      Pediatric Points of Interest (POI) and a combination of a questionnaire, unique
      user identifier and link-tracking system to collect data about POI patrons'
      demographics and Internet resource utilization. During a five week period, 5216
      individuals visited the POI and requested 36,187 links. The majority of users had
      less than one year of Internet experience and were first-time visitors to the
      POI. More than 83% of users were from North America. Medical professionals were
      more likely to return to the POI during the study period and reported visiting
      the POI mainly for 'medical education', 'research', 'resource identification',
      and 'disease specific information'; they proceeded primarily to the resource
      categories 'Medical Institutions and Agencies' (32%) and 'Professional Education
      and Resources' (28%). Laypersons expressed the greatest interest in 'disease
      specific information' and 'patient education' and most frequently visited the
      category. 'Patient Education' (42%). On average, users were able to identify
      resources related to their stated goals within one level of searching. Health
      care providers and other web patrons are actively utilizing Internet sites to
      seek medical information and are able to identify resources with a minimum of
      searching.

PMID- 9618684
TI  - Webifying a patient interview support application.
AB  - This paper reports on the software engineering challenges, and resultant benefits
      experienced, in porting an interactive, knowledge-based system from Microsoft
      Windows to the World Wide Web for evaluation purposes. The Patients Interview
      Support Application (PISA) is a program intended for operation by a non-expert
      clerk to interview an ambulatory primary care patient. The PISA code had to be re
      written substantially to address the 'connectionless' nature of Web dialog and to
      work in terms of dynamically generated HTML forms; however, it was possible to
      avoid any revision of the central knowledge-base or inference engine. The
      resultant Web environment attracted thought-provoking and detailed feedback from
      users, indicating that significant attention can be obtained from the global
      community by mounting an interactive system on the Web. Specific enhancements to
      the PISA's artificial intelligence are suggested by user reaction. A future
      global health informatics 'marketplace' with a multidue of Web-based system
      components available for composition of health information systems is envisioned.

PMID- 9618685
TI  - A web interface for multimedia electronic patient record: consensual validation
      of the Aquitaine Health Information Network prototypes.
AB  - The PromptPR patient record originates from the research and development project
      DILEMMA (1992-94) and has been undertaken in the context of the research project
      PROMPT (4th Framework Health Telematics). Here we present the work undertaken
      with the doctors of the project RISA (Reseau d'Information de Sante en Aquitaine)
      in order to adapt the patient record to their various practical medical
      conditions. Effectively, there are implications for general practitioners, the
      private sector and hospital personnel. The richness of the workgroup and the
      adoption of a participative methodology, guided by the demands of the end-users
      allowed the creation of an electronic patient record (EPR) sufficiently simple
      and generic as to serve as a common base for both general practitioners and
      hospital medical staff. Independent of this system, the multimedia interface
      presented is based on frames, which enables visualization of the EPR either
      vertically or horizontally, with access to both the multimedia and external
      documentation of the patient. This web interface is the result of a consensus of
      opinion within the group.

PMID- 9618686
TI  - Research-oriented image registry for multimodal image integration.
AB  - To provide multimodal biomedical images automatically, we constructed the
      research-oriented image registry, Data Delivery System (DDS). DDS was constructed
      on the campus local area network. Machines which generate images (imagers: DSA,
      ultrasound, PET, MRI, SPECT and CT) were connected to the campus LAN. Once a
      patient is registered, all his images are automatically picked up by DDS as they
      are generated, transferred through the gateway server to the intermediate server,
      and copied into the directory of the user who registered the patient. DDS informs
      the user through e-mail that new data have been generated and transferred. Data
      format is automatically converted into one which is chosen by the user. Data
      inactive for a certain period in the intermediate server are automatically
      achieved into the final and permanent data server based on compact disk. As a
      soft link is automatically generated through this step, a user has access to all
      (old or new) image data of the patient of his interest. As DDS runs with minimal
      maintenance, cost and time for data transfer are significantly saved. By making
      the complex process of data transfer and conversion invisible, DDS has made it
      easy for naive-to-computer researchers to concentrate on their biomedical
      interest.

PMID- 9618687
TI  - Toward a new natural medicine.
AB  - Treatments summarized under the term "natural medicine," i.e., those offered as
      an alternative or in addition to conventional medicine, have enjoyed a surge in
      popularity in recent years. The "natural" descriptor employed in connection with
      these healing methods is frequently misunderstood, leading to underestimation of
      the risks arising from incorrect use. However, the essential principle underlying
      traditional natural medicine, mobilization of the body's own forces against
      disease, is increasingly being employed in a new, rational form of medicine:
      molecular medicine. A range of natural endogenous substances for medical use are
      already available. Human proteins such as erythropoietin can now be produced as
      medicines in highly pure form with the aid of genetic engineering techniques. Our
      increasing understanding of the function of our genes and the resulting
      descriptions of molecular mechanisms underlying disease are also helping us to
      utilize the body's own construction set. New techniques such as gene therapy will
      in future enable us to reproduce the natural conditions in the healthy body with
      increasing specificity in our attempts to cure illnesses. One such application
      will be the activation of the immune system to combat cancer. The complete
      decoding of the human genome will not only allow illnesses to be described, and
      possibly prevented, at an earlier stage. Illnesses will also be able to described
      more precisely and individually at the molecular level, opening up the
      possibility of targeted, patient-specific cures.

PMID- 9618688
TI  - A novel circuit in the bat's midbrain recruits neurons into sound localization
      processing.

PMID- 9618689
TI  - Relationship between period and phase angle differences in Mus booduga under
      abrupt versus gradual light-dark transitions.

PMID- 9618690
TI  - The temporal profile and morphologic features of neuronal death in human stroke
      resemble those observed in experimental forebrain ischemia: the potential role of
      apoptosis.
AB  - Although neuronal death has been studied in experimental models of ischemia, the
      precise mechanisms regulating cell death remain unclear. Furthermore, the timing
      and pattern of neuronal death in human stroke has not been extensively studied.
      To further our understanding of ischemia-induced neuronal death, we examined the
      temporal profile of histochemical and morphologic characteristics of hippocampal
      neuronal death following experimental forebrain ischemia and compared these
      findings to human brain specimens obtained from subjects suffering cerebral
      infarction. Transient forebrain ischemia (TFI) was induced in normothermic adult
      rats by bilateral carotid artery occlusion combined with hypotension. Animals
      were sacrificed at 6, 12, 18, 24, 48, and 72 h and 7, 14, and 28 days following
      ischemia (n = 4 at each time point). Experimental tissue was analyzed using light
      and electron microscopy as well as TUNEL histochemistry. A total of 27 human
      brain specimens with neuropathological confirmation of ischemic damage and
      appropriate controls were also examined using light microscopy and TUNEL
      histochemistry. Dense TUNEL staining in hippocampal CA-1 neurons was present at
      48 and 72 h following experimental ischemia. Prior to these times, little or no
      nuclear staining was noted and after 72 h nuclear staining diminished rapidly.
      Ultrastructural findings at these time points demonstrated many features similar
      to those seen in cells undergoing apoptosis, such as cell shrinkage with
      increased electron density, chromatin condensation with formation of
      heterochromatin, intact plasma membranes, and intact intracellular organelles. In
      a similar fashion, human stroke specimens during the subacute period showed dense
      nuclear TUNEL staining in penumbral neurons, whereas in the acute or chronic
      stages little or no staining was noted. Our results demonstrate that the timing
      of morphologic changes and TUNEL histochemistry following human stroke resembles
      that observed in experimental TFI. Furthermore, neuronal death in both
      experimental ischemia and human stroke share several features characteristic of
      apoptotic cell death.

PMID- 9618691
TI  - The interest of surgical closure of patent foramen ovale after stroke: a
      preliminary open study of 8 cases.
AB  - The risk of stroke and the risk of recurrent strokes in patients with patent
      foramen ovale (PFO) need a prevention that still remains a therapeutic problem.
      There are 4 preventive treatments: anti-agregants, anti-coagulants, transcatheter
      closure, and surgical closure of PFO. The aim of this study was to demonstrate
      that surgical closure of PFO is safe and useful for prevention of strokes. Eight
      patients with stroke and PFO diagnosed by transesophageal echography (TEE) were
      prospectively selected for surgical closure. It was necessary to be younger than
      70 years, not to have another cause of stroke, and to have either recurrent
      strokes or several ischemic lesions on MRI, isolated for PFO associated with an
      atrial septal aneurysm, and to have a Valsalva maneuver or cough inducing the
      stroke. For these reasons, these patients were considered to be an homogenous
      group with a strong relationship between the PFO and the stroke, and with a high
      risk of recurrence of stroke. The 8 patients had a direct suture of the PFO with
      a cardiopulmonary bypass. All patients were followed-up with clinical, MRI and
      TEE examinations during 12 months after surgery. No surgical complications were
      observed. After one year, without any anticoagulant treatment, no recurrent
      stroke or transient ischemic attack, no new ischemic lesions on MRI, nor
      neuropsychological disturbance were noted. No post-surgical inter-atrial right-to
      left shunting was observed. In the absence of controlled studies to guide
      therapeutic options, our data suggest that surgical closure of PFO in patients
      with stroke, is safe and efficacious to prevent recurrent stroke without any
      anticoagulants in the first year of follow-up. Further studies are needed to
      evaluate the long-term role of surgical closure of PFO as an alternative to
      prolonged anti-thrombotic treatment.

PMID- 9618692
TI  - Mutual link among the approaches to clipping of basilar aneurysms.
AB  - The pterional approach for basilar aneurysm clipping, has become the most common
      approach among surgeons, since it was advocated by Yasargil in 1982. However,
      other approaches aiming at an adequate but less invasive surgery to meet
      conditions of peripheral blood vessels (including aneurysmal size, direction and
      perforating arteries and arteriosclerosis) and the direction of clip insertion
      have also been developed. The approaches will be recommended to be expanded
      according to situations of the actual intra-operative findings in the future. The
      mutual link among the approaches to clipping of basilar aneurysms was
      investigated.

PMID- 9618693
TI  - Cutaneous T-cell lymphoma with intracerebral and bilateral intraocular spread.
AB  - Brain metastasis from systemic or cutaneous lymphoma is infrequently encountered.
      We present a case report of cutaneous T-cell lymphoma (CTCL) that metastasized to
      the brain. A literature review identified fourteen other cases of brain
      infiltration with CTCL. This report focuses attention on the typical presentation
      and markedly poor prognosis that characterize this rare problem. It also
      emphasizes the suspicion with which a brain mass in a lymphoma patient with
      neurological changes should be regarded.

PMID- 9618694
TI  - Pulsed off-resonance magnetization transfer for brain tumor in patients.
AB  - We investigated the clinical applicability of pulsed off-resonance magnetization
      transfer (MT) technique in magnetic resonance (MR) imaging for the estimation of
      the histological feature of brain tumor. The parameters were optimized using
      bovine serum albumin (BSA) solutions and gels in 1.5-tesla MR system as follows:
      TR, 50 msec; TE, 5 msec; flip angle, 30 degree; offset frequency, 1000 Hz. MT
      effect was evaluated by measuring the MT ratio (MTR) and reconstructing
      calculated MTR color image. The MTRs of the BSA solutions and gels increased with
      increasing concentrations of protein, while the MTRs of the gels were remarkably
      higher than those of the solutions. The optimized sequence was performed in 20
      healthy volunteers and 30 patients with brain tumors. In normal brains, the MTRs
      were significantly higher in white matter than in gray matter (p < 0.05). The MTR
      in brain tumor was significantly lower than that in normal brain tissue (p <
      0.05) and the calculated MTR image produced contrast between brain tumor and
      normal brain tissue. There was a statistically significant difference in MTR
      between benign (0.30 +/- 0.05, n = 17) and malignant (0.26 +/- 0.04, n = 13)
      tumors (p < 0.05). The optimized MT technique is quite sensitive for estimating
      the degree of intermolecular interaction between macromolecules and water within
      the central nervous system.

PMID- 9618695
TI  - Kinematics of fast wrist movements in manic-depressive illness chronically
      treated with lithium carbonate.
AB  - Lithium salts have been shown to impair kinematics of fast voluntary movements
      during acute intoxication. The aim of the present study was to determine whether
      lithium carbonate affected the kinematics of fast movements in patients
      chronically treated and who did not exhibit signs of neurotoxicity. We analysed
      fast wrist flexion movements in 6 healthy subjects, in 5 patients presenting a
      manic-depressive illness without treatment, and in 8 patients receiving lithium
      carbonate for a manic-depressive disease. The mean duration of treatment was 3.9
      +/- 4.1 years, the mean daily dose 837 +/- 341 mg and the mean serum level 0.95
      +/- 0.15 mEq/l. Although mean movement amplitudes were similar in the 3 groups,
      the variability of fast movements was increased in patients receiving lithium
      salts. The ratio of maximum to average velocities (Vm/Vave) was significantly
      higher in patients treated, and their movements were temporally asymmetrical,
      with a ratio of acceleration duration divided by deceleration duration being
      lower than in the 2 other groups. These kinematic abnormalities show that a
      chronic treatment with lithium salts is associated with an impairment of the
      cerebellar control of fast single-joint movements.

PMID- 9618696
TI  - Computational imaging of cerebral perfusion by real time processing of DSA
      images. Clinical applications.
AB  - Real time and high resolution functional imaging of cerebral perfusion was
      developed, which displays the color coded image of the cerebral perfusion index
      (PI) from the serial images of digital subtraction angiography (DSA). The small
      (3 x 3 pixels) regions of interest (ROI) were set on the images, and the time
      density curves of the contrast media for each ROI were obtained. The perfusion
      indices, corresponding to the mean transit time (MTT), were calculated for all
      the ROIs on the image in real time (5 sec) by the area over height method and
      then, converted to the PI image. A large ROI (64 x 64 pixels) was also used to
      estimate the parenchymal perfusion. In the normal subjects, consistent PI values
      at the various parts of the cerebral arteries were obtained, which reasonably
      agreed with the published values when converted to the blood flow. Then the study
      on the pathological subjects were made. Firstly, the alteration in the PI images
      agreed well with the CBF SPECT study in the case of moyamoya disease with the
      synangiosis operation. Secondly, even a 5% change of the parenchymal perfusion
      could be detected with the PI imaging, which was obscure when inspecting the
      series of DSA images, in the case of intra-arterial papaverine infusion for
      delayed vasospasm. Thirdly, the vortex inside a large aneurysm could be estimated
      with the same resolution as DSA. Our method offers real time, high resolution,
      projection angle independent and semiquantitative imaging of the cerebral
      perfusion from the conventional DSA images without introducing any new expensive
      devices. This method could be used to evaluate the therapeutic change and
      especially to monitor the rapidly changing cerebral perfusion in interventional
      angiography.

PMID- 9618697
TI  - Ameliorative effect of glial cell line-derived neurotrophic factor on brain edema
      formation after permanent middle cerebral artery occlusion in rats.
AB  - Glial cell line-derived neurotrophic factor (GDNF) was applied topically on the
      brain surface immediately after permanent middle cerebral artery (MCA) occlusion
      in rats. In contrast to the cases treated with vehicle, a formation of brain
      edema was significantly reduced at one day by the treatment with GDNF. Terminal
      deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling
      (TUNEL) staining was markedly reduced in the cases with GDNF treatment at 12 h
      after MCA occlusion. However, the induction of immunoreactive 70-kd heat shock
      protein (HSP70) was slightly ameliorated by the GDNF treatment. The present
      results suggest that the treatment with GDNF has a significant effect on
      ameliorating brain edema formation after continuous brain ischemia, and the
      effect is greatly associated with the reduction of apoptotic changes, but
      slightly with that of stress response of cells.

PMID- 9618698
TI  - Cisternal CSF levels of cytokines after subarachnoid hemorrhage.
AB  - Cytokines are considered as mediators of immune and inflammatory responses.
      Cisternal CSF levels of interleukin (IL)-6, IL-8, monocyte chemoattractant
      protein-1 (MCP-1) and of the soluble adhesion molecule E-selectin were evaluated
      in patients operated on for intracranial aneurysms. Cisternal CSF samples were
      obtained at surgery in 41 selected patients (31 with diagnosis of subarachnoid
      hemorrhage (SAH) and 10 control patients operated on for incidental unruptured
      aneurysms); 14 patients were operated within 72 h after SAH (early surgery) and
      17 were operated after day 10 after the hemorrhage (delayed surgery). The CSF
      levels of cytokines were evaluated using radioimmunoassay and their
      concentrations were related to the timing of surgery, the amount of cisternal
      subarachnoid blood clots and the onset of clinical and angiographical evidence of
      arterial vasospasm. Mean cisternal CSF levels of IL-6, IL-8 and AMCP-1 are
      significantly higher in samples obtained from patients early operated after SAH,
      while levels of E-selectin were below the threshold value of the method in all 41
      cases. In the early operated group 7 patients presented symptomatic vasospasm:
      levels of IL-8 and MCP-1 were not significantly different were compared to those
      of uncomplicated cases; on the other hand, significantly higher levels of IL-6
      were shown in the subgroup of patients operated within 72 h after SAH and
      developing vasospasm. Among the patients undergoing delayed surgery 5 presented
      symptomatic vasospasm, but no significant difference was shown in cisternal CSF
      levels of cytokines measured. The results of the present study show that in
      patients with unruptured aneurysms cytokines are present in cisternal CSF in
      scarce quantities and that in subarachnoid spaces after SAH there is an
      impressive increase of IL-6, IL-8 and MCP-1. Moreover, the higher cisternal CSF
      levels of IL-6 found in the early stage after SAH might have a predictive value
      regarding the occurrence of symptomatic vasospasm.

PMID- 9618699
TI  - Anoxic depolarization determines ischemic brain injury.
AB  - To clarify the role of anoxic depolarization (AD) in ischemic brain injury, we
      examined the correlation between AD and ischemia-induced neuronal injury. Twenty
      eight rats underwent transient forebrain ischemia with lowering of blood pressure
      and bilateral carotid occlusion while direct current shifts, electrocorticogram,
      and cortical blood flow (CoBF) were epidurally recorded from the right parietal
      cortex. One week later the right parietal cortex was studied histopathologically.
      AD appeared 0.5-3.0 min after carotid occlusion in 21 of 28 animals. Circulation
      was reinitiated 15 min after AD onset in 11 rats (group A) and 10 min after onset
      in 10 rats (group B). AD did not develop during 20 min of ischemia in 7 rats
      (group C). All 12 rats (6 from group A and 6 from group B) in which CoBF
      decreased below 9.5% of control flow exhibited AD. Histopathologic examination
      disclosed massive neuronal necrosis in 5 of the 6 group A animals with marked
      flow reduction but in none from group B. CoBF fell between 9.5% and 20% in 14
      rats, among these, AD appeared in 9 (5 from group A and 4 from group B) but not
      in 5 (group C). Massive neuronal necrosis was demonstrated in 3 of 5 rats from
      group A. Ischemic neuronal changes were absent or minimal in only 1/5 of group A
      animals, a much lower fraction than in group B (4/4, p < 0.05) or in group C
      (5/5, p < 0.05). When CoBF remained above 20% of control flow during ischemia (2
      rats) no AD or irreversible injury occurred. The present study suggests that AD
      is a more reliable determinant of irreversible brain injury than degree of CBF
      reduction, and also demonstrates that 15 min is the critical duration of AD for
      irreversible brain injury at brain temperatures around 37 degrees C.

PMID- 9618700
TI  - Local fibrinolysis and aspiration of intracerebral hematomas in rats. An
      experimental study using MR monitoring.
AB  - Serial magnetic resonance (MR) imaging has not yet been validated in the therapy
      of experimental intracerebral hematomas in a rat model. It is possible to test
      the effect of local fibrinolysis and aspiration on the clot volume using serial
      magnetic resonance imaging and different MR-sequences. Experiments were carried
      out in 22 male Sprague-Dawley rats. Intracerebral hematoma was produced by
      injection of fresh autologous blood into the caudate nucleus using a double
      injection technique. Thirty minutes later 10 rats were treated by injecting 12
      microliters of recombinant tissue plasminogen activator. MR-imaging was performed
      immediately after generation of the hematoma and after clot lysis. The clot
      volume measured in the magnetic resonance images was compared with that obtained
      in stained histological serial sections at the end of the experiment. Serial MR
      scanning demonstrated a significant reduction (p < 0.01) of hematoma volume after
      fibrinolysis followed by aspiration of the blood clot. The best correlation
      between MR- and histological volumetry was found on RF-spoiled FLASH 2D-images.
      This study documents the efficacy of MRI in detecting and delineating the size of
      acute intracerebral hematomas and its time course. Local fibrinolysis and
      aspiration can be simulated in an experimental rat model.

PMID- 9618701
TI  - Early protective effects of Iloprost after experimental spinal cord injury.
AB  - This investigation was undertaken to study the early protective effects of
      Iloprost, a stable analogue of prostacyclin, after spinal cord injury in rabbit.
      Sixteen adult male rabbits (New Zealand Albino) were injured by application of
      epidural aneurysm clip. Eight rabbits received an intravenous (i.v.) infusion of
      30 micrograms kg-1 Iloprost, and eight rabbits received an infusion of saline
      (SF). Treatment with Iloprost started immediately after spinal cord injury and
      continued for one hour. Evoked potentials were recorded for each rabbit at one,
      15, and 60 minutes after the spinal cord injury. Twenty-four hours later, all the
      rabbits were deeply anesthetized and spinal cords were removed for
      histopathological examinations. There was no meaningful statistical difference
      between cortical somatosensorial evoked potentials (CSEP) of the saline and
      Iloprost group. However, light and electron microscopic studies showed that the
      Iloprost treated group had moderate protection of myelin and axons; and limited
      edema. These results suggest that intravenous Iloprost treatment after spinal
      cord injury has a highly protective effect without any side effects.

PMID- 9618702
TI  - Subcellular localization of phosphoprotein B-50 in regenerating muscle. An immuno
      electron microscopic study.
AB  - Phosphoprotein B-50, also termed growth-associated protein GAP43, is a membrane
      bound phosphoprotein expressed in neurons. It is particularly abundant during
      periods of axonal outgrowth in development and regeneration of the central and
      peripheral nervous systems. Recently the expression of phosphoprotein B-50 in
      regenerating muscle fibers was reported and it was assumed that phosphoprotein B
      50, in muscles, plays a role in the determination of the growth morphology of
      regenerating muscle fibers. Thus, phosphoprotein B-50 no longer can be regarded
      as a neuron-specific molecule. In this paper we study the subcellular
      localization of phosphoprotein B-50 in regenerating human skeletal muscle fibers
      by electron immunohistochemistry. Phosphoprotein B-50 immunoreactivity is
      randomly distributed over the nuclear and perinuclear area of regenerating muscle
      fibers. Previously, by light-microscopy phosphoprotein B-50 immunoreactivity was
      demonstrated on the inner face of the sarcolemma in hypotrophic type 1 fibers in
      congenital fiber type disproportion. It is this distribution of phosphoprotein B
      50 in developmentally disordered myocytes in particular which allows an analogy
      to the corresponding results found for growing axons. But we did not find
      subsarcolemmal expression of B-50 in regenerating muscle fibers. Probably this
      indicates that there is a difference in B-50 expression between regeneration of
      muscle fibers and developmentally retarded/immature myofibers. The presented data
      suggest that phosphoprotein B-50 is inserted only stage-dependent in the
      extending sarcolemma of the growing muscle fiber. Analogously to the nervous
      system, phosphoprotein B-50 may serve a local function involving transmembrane
      signalling by means of calmodulin binding of phosphoprotein B-50 and/or
      phosphoprotein B-50 phosphorylation and dephosphorylation.

PMID- 9618703
TI  - The effect of trapidil on the reactive astrocytic proliferation following spinal
      cord trauma in rats: light and electron microscopic findings.
AB  - Platelet-derived growth factor (PDGF) released from platelets is one of the
      mitogens in serum, which plays a major role upon the cell biology, namely
      enhancing cell division and controlling of the maturation, especially upon the
      glial cell growth and its differentiation. Trapidil, which is an anti-PDGF agent,
      inhibits the effect of PDGF, especially the proliferative effects on the glial
      and tumoral cells in vitro. Previous studies suggested that the astrocytic
      proliferation stimulated by PDGF was inhibited by trapidil via the selective
      antagonism. Trapidil was not found to have a considerable effect on the
      prevention of nonpermissive astrocytes in this study. It should be theorized that
      trapidil, administered immediately even after the trauma, could not reach the
      injury site in effective measure because of secondary events such as edema and
      impairment of blood circulation. This suggestion should be another subject for
      studies concerning trapidil which is administered prior to the trauma.

PMID- 9618704
TI  - [Airway autonomic nervous system dysfunction and asthma].
AB  - Airways are richly innervated by 4 nervous systems: adrenergic, cholinergic,
      inhibitory nonadrenergic noncholinergic (i-NANC), and excitatory NANC (e-NANC)
      nervous systems. Dysfunction or hyperfunction of these systems may be involved in
      the inflammation or airway hyperresponsiveness observed in asthmatic patients.
      The cholinergic nervous system is the predominant neural bronchoconstrictor
      pathway in humans. Airway inflammation results in exaggerated acetylcholine
      release from cholinergic nerves via dysfunction of the autoreceptor, muscarinic
      M2, which is possibly caused by a major basic protein or IgE. Vasoactive
      intestinal peptide (VIP) and nitric oxide (NO) released from i-NANC nerves act as
      an airway smooth muscle dilator. The effects of VIP and NO are diminished after
      allergic reaction by inflammatory cell-mediated tryptase and reactive oxygen
      species. Thus, in asthmatic airways, the inflammatory change-mediated neural
      imbalance may result in airway hyperresponsiveness. Tachykinins derived from e
      NANC nerves have a variety of actions including airway smooth muscle contraction,
      mucus secretion, vascular leakage, and neutrophil attachment; and they may be
      involved in the pathogenesis of asthma. Since tachykinin receptor antagonists are
      effective for bradykinin- and exercise-induced bronchoconstriction in asthmatic
      patients, these drugs may be useful for asthma therapy.

PMID- 9618705
TI  - [Possible role of nitric oxide in NANC relaxation of the airway and in airway
      hyperreactivity in airway disease].
AB  - In the lung, there is increasing evidence that endogenous nitric oxide (NO) plays
      multiple roles in physiological control of airway functions, immune responses and
      host defense against infection, and it is also implicated in inflammatory disease
      of the airways. As elsewhere, it is generally accepted that NO derived from
      constitutive NO synthase (cNOS) is involved in physiological regulation of airway
      function, whereas NO derived from inducible NO synthase (iNOS) is involved in
      immune responses and inflammatory diseases of the airway. In this mini review,
      first we describe evidence showing the possible roles of NO and NO-related
      compounds in nonadrenergic noncholinergic (NANC) relaxation and inhibitory action
      on excitatory neuro-effector transmission, thereby indicating that NO derived
      from neuronal cNOS plays a role to provide "double braking" in
      bronchoconstrictions. Secondly, we will discuss the possible involvement of
      epithelial damage due to excessive NO production through iNOS in the genesis of
      airway hyperreactivity and airway inflammation.

PMID- 9618706
TI  - [Histamine in the pathogenesis of asthma].
AB  - While it is clear that the clinical expression of IgE-mediated diseases depends
      upon the actions of multiple mediators, histamine, the earliest recognized
      mediator of allergy, remains a prominent contributor. Histamine released from
      mast cells binds to specific receptors (H1, H2, H3) to produce its clinical
      effects. The cardinal features of asthma include smooth muscle spasm, mucosal
      edema, inflammation and mucus secretion. It has been demonstrated that two of
      these features, bronchospasm and mucosal edema, can be caused by H1-receptor
      stimulation, while H2- and possibly H1-activation are probably minor causes of
      mucus secretion. Histamine interacts directly with the endothelial cells (EC) and
      induces permeability, a transient expression of P-selectin and the secretion of
      lipid mediators (e.g. PGI2, PAF and LTB4). Moreover, histamine induces a
      significant increase of IL-6 and IL-8 secretion by EC. Since IL-8 exerts a
      chemotactic activity for neutrophils, eosinophils and basophils, and IL-6 is
      involved in endothelium permeability, the secretion of cytokines may be involved
      in the late phase reaction. Some antihistamines (i.e., levocabastine,
      terfenadine, loratadine, azelastine and oxatomide) can reduce ICAM-1 expression.
      The participation of histamine in the allergic inflammation, including asthma,
      must be re-examined, since the effects of histamine are more widespread.

PMID- 9618707
TI  - [Role of peptide-leukotrienes in bronchial asthma].
AB  - Peptide-leukotrienes (p-LTs) (LTC4, LTD4 and LTE4) are major metabolites of the
      arachidonate 5-lipoxygenase pathway. Although a number of papers have reported
      that p-LTs induce potent bronchial smooth muscle constriction as well as airway
      mucus secretion, vascular permeability and proliferation of airway smooth muscle
      cells, it had not been recognized that they are pivotal chemical mediators in
      asthmatic diseases until recently. Yet, several potent and selective antagonists
      against p-LTs and inhibitors of p-LT formation revealed that p-LTs play
      significant roles in not only allergic but non-allergic asthma including exercise
      and aspirin-induced asthma. In addition, it has been reported that p-LTs
      participate in rhinitis, especially nasal blockage. In this article, recent
      development of drugs relating to p-LTs and their therapeutic effects for asthma
      are mainly reviewed.

PMID- 9618708
TI  - [The role of cytokines and arachidonic acid metabolites in the development of
      airway hyperresponsiveness].
AB  - Bronchial asthma is considered to be a chronic airway inflammatory disease
      influenced by genetics and environmental factors. Airway hyperresponsiveness
      (AHR) is a characteristic of the disease generally associated with airway
      inflammation. Recently, the potential targets for therapeutic intervention in AHR
      has focused on the inhibition or antagonism of lipid mediators including
      leukotrienes, thromboxanes and platelet-activating factor. Furthermore, the
      inhibition of Th2 cytokines, such as interleukin-4 or interleukin-5, is another
      target for the prevention of AHR. In the present review, we describe the role of
      cytokines and arachidonic acid metabolites in the onset and development of AHR.

PMID- 9618709
TI  - [Involvement of kinin and tachykinin in airway hyperreactivity].
AB  - Airway hyperreactivity (AHR) is an important characteristic feature of asthma.
      Recently, it has been recognized that airway inflammation underlies the
      phenomenon of AHR. Kinins such as bradykinin (BK) and kallidin (KD) have been
      implicated as mediators of airway inflammatory diseases. Tachykinins such as
      substance P (SP) and neurokinin A (NKA) produce a variety of effects on the
      airways. These effects include changes in bronchomotor tone, vasodilatation,
      increase in vascular permeability and facilitation of the release of other
      transmitters. Non-cholinergic responses are due to release of neuropeptides such
      as tachykinins from sensory nerve endings. Kinins and tachykinins have been
      implicated in neurogenic inflammation. The O3 exposure (3 ppm, 30 min) induced
      AHR to ACh in guinea pigs. The O3-induced AHR was significantly enhanced by
      pretreatment with captopril, a kininase II inhibitor. Infusion of subthreshold
      dose of BK and KD developed AHR to ACh. The O3-induced AHR was significantly
      inhibited by pretreatment with capsaicin. Infusion of the subthreshold dose of SP
      and NKA developed an AHR to ACh. The KD-induced AHR was inhibited by pretreatment
      with capsaicin. Kinins and tachykinins may be therefore involved in the O3
      induced AHR, and kinins may act through tachykinin intervention on the O3-induced
      AHR.

PMID- 9618710
TI  - [Molecular mechanisms of the hyperresponsiveness of airway smooth muscle in
      bronchial asthma].
AB  - Nonspecific airway hyperresponsiveness (AHR) is a common feature of allergic
      bronchial asthmatics, but the underlying mechanisms of AHR have yet to be
      elucidated. The importance of AHR in the pathogenesis of asthma has been
      suggested by its relevance to the severity of this disease. There is thus a need
      to understand the underlying mechanisms of AHR for the sake of asthma therapy. In
      allergic asthmatics, airway smooth muscles (ASMs) obtained from in vivo
      hyperresponsive patients have in vitro hyperresponsiveness to cholinergic
      agonists. It is therefore possible that the mechanisms responsible for the AHR
      exist, at least in part, on the ASM site. Although ASM is known to contract in
      response to acetylcholine via muscarinic M3 receptors and this contractile
      response is augmented during AHR, no alteration in muscarinic receptor density in
      ASM has been demonstrated in various AHR models. It is thus likely that augmented
      intracellular signaling might be a possible reason for the AHR. In fact, recent
      investigations demonstrated increases in the levels of GTP binding protein, Ca2+
      mobilization and inositol 1,4,5-trisphosphate generation and so on in
      hyperresponsive ASM.

PMID- 9618711
TI  - [Airway hypersecretion and mucociliary dysfunction in asthma].
AB  - Mucociliary transport function can be determined by ciliary motility of airway
      epithelial cells, the amount and physicochemical properties of airway surface
      fluid, and the airway integrity. Mucus glycoprotein is released from submucosal
      glands and goblet cells in response to a variety of stimuli and, on other hand,
      water is secreted by airway epithelial cells through the movement of
      electrolytes. Marked airway goblet cell hyperplasia has been found in patients
      who died of severe asthma, indicating that goblet cell hypersecretion may play a
      significant role in the formation of mucus plugs in the respiratory tract. Goblet
      cell secretion is regulated by autonomic nerves and various chemical mediators
      associated with asthma. Antigen challenge causes an increase in mucus discharge
      from goblet cells in ovalbumin-sensitized animals, and this effect can be greatly
      inhibited by an histamine H2-receptor antagonist. Similarly, histamine released
      by antigen challenge stimulates airway epithelial Cl secretion and, hence, water
      secretion toward the airway lumen. There is ample evidence that mucociliary
      clearance is impaired in patients with asthma, which results in deterioration of
      airflow limitation. The precise mechanism for this impairment remains uncertain,
      but bronchospasm and the increased mucus secretion induced by peptide
      leukotrienes may be involved.

PMID- 9618712
TI  - [Effects of an antidiarrhoeica containing an extract from geranium herb on
      astringent action and short-circuit current across jejunal mucosa].
AB  - A consists of berberine chloride and an extract from geranium herb. To clarify
      mechanisms of the antidiarrheal effect of Phelloberin-A, we investigated the
      astringent action by determining its binding activity to rabbit hemoglobin and
      effects on active transport, which was indicated by short-circuit current (Isc),
      in rat jejunum by the Ussing chamber technique. The effects of berberine chloride
      and geranium herb on both the binding activity to hemoglobin and the
      electrophysiological parameters such as Isc were compared with those of the
      antidiarrhoeicas, tannic acid, albumin tannate and bismuth subnitrate. Geranium
      herb, tannic acid and bismuth subnitrate increased significantly the binding
      activity to hemoglobin at concentrations of > 1 mg/ml, > 0.3 mg/ml and 10 mg/ml,
      respectively, but berberine or albumin tannate did not. Geranium herb and tannic
      acid dose-dependently and moderately increased Isc in rat jejunal mucosa and the
      increase became significant at a concentration of 10 mg/ml. Neither berberine
      chloride, albumin tannate nor bismuth subnitrate affected Isc. In contrast,
      cholera toxin, which increases the secretion from intestinal mucosa to the lumen
      and induces diarrhea, decreased Isc at a concentration of 0.1 mg/ml. The decrease
      of Isc induced by cholera toxin was antagonized by pretreatment with geranium
      herb (10 mg/ml), indicating that geranium herb inhibited the toxin-induced
      increase in secretion. These results suggest that geranium herb possesses an
      astringent action and moderately increases Isc across the intestinal mucosa.
      Therefore, the effects may support an antidiarrheal effect of both geranium herb
      and Phelloberin-A.

PMID- 9618713
TI  - Triple-marker test as screening for Down syndrome: a meta-analysis.
AB  - The effectiveness of triple-marker testing as screening for Down syndrome needs
      to be evaluated by means of formal meta-analytic techniques. We did a MEDLINE
      search to identify studies evaluating the detection of Down syndrome by use of
      the triple-marker test. Reference lists of articles were also checked. Papers
      published in either English, French, or German from 1966 to November 1996 were
      eligible for this review. Twenty cohort studies were identified. Results of
      sensitivities and false-positive rates from different subgroups of the study
      sample were compared by using summary receiver-operating characteristic curve
      analysis. Medians of sensitivities and false-positive rates were also estimated.
      A total of 194,326 patients were included. In women of all ages, the medians for
      sensitivities were 67, 71, and 73 percent when the cutoffs used were 1:190-200,
      1:250-295, and 1:350-380, respectively. The median false-positive rates
      fluctuated between 4 and 8 percent. For women at or above 35 years old, the
      medians of sensitivity and false-positive rate were 89 and 25 percent,
      respectively, when the chosen cutoff was 1:190-200. In patients below 35 years
      old, the median sensitivity was 57 percent if the cutoff used was 1:250-295.
      Summary receiver-operating characteristic curves showed that 1:190 was the best
      cutoff for predicting Down syndrome. The triple-marker testing is an effective
      screening method of detecting Down syndrome pregnancies. It is less effective in
      younger than in older age groups and may be offered as an alternative to
      amniocentesis to pregnant women over 35.

PMID- 9618714
TI  - Immune maladaptation in the etiology of preeclampsia: a review of corroborative
      epidemiologic studies.
AB  - Genuine preeclampsia is a disease of first pregnancies. The protective effect of
      multiparity, however, is lost with change of partner. Also, exposure to semen
      provides protection against developing preeclampsia. Analogous to altered
      paternity, artificial donor insemination and oocyte donation are reported to
      result in a substantial increase of preeclampsia. Thus, epidemiologic studies
      strongly suggest that immune maladaptation is involved in the etiology of
      preeclampsia. Although the exact etiology of preeclampsia remains unknown, the
      conclusions derived from epidemiologic studies may have consequences for
      practicing physicians: 1) according to the primipaternity concept, a multiparous
      women with a new partner should be approached as being a primigravid women; 2)
      artificial donor insemination and oocyte donation are associated with an
      increased risk of developing pregnancy-induced hypertensive disorders; 3) a more
      or less prolonged period of sperm exposure provides a partial protection against
      pregnancy-induced hypertensive disorders. In the 1990s, all women with changing
      partners are strongly advised to use condoms to prevent sexually transmitted
      diseases. However, a certain period of sperm exposure within a stable relation,
      when pregnancy is aimed for, is associated with a partial protection against
      preeclampsia.

PMID- 9618715
TI  - Periurethral injection for the treatment of urinary incontinence.
AB  - Periurethral injection of substrates that compress, support, or narrow the
      bladder neck for the treatment of stress incontinence is not new. Several
      injectable compounds have been used in a small number of patients during the
      1940s and through the 1960s; however, the results were not very successful and
      often led to significant complications. More recently, two major materials have
      been developed that seem to be useful in treating stress incontinence by
      periurethral injection: Polytef paste and GAX collagen. Other injectables include
      autologous fat tissue and silicone microimplants. The most suitable patients for
      periurethral injection are elderly women, patients who constitute high operative
      risk, and those with stress incontinence due to intrinsic sphincter failure.
      Patients with stress incontinence due to a combination of urethral hypermobility
      and intrinsic sphincter deficiency with failure of suspension procedure may also
      benefit from the procedure. The reported long-term (more than 24 months) success
      rates according to the various substances are as follows: Teflon (Polytef)
      (E.I.du Pont de Nemours and Co, Wilmington, DE): 30 to 38 percent cured or
      improved; repeated injections usually do not improve the outcome; mostly minor
      complications with case reports of more serious side effects such as periurethral
      granuloma formation and bladder outlet obstruction. GAX collagen: 69 to 77
      percent subjectively cured or improved after 24 months; 54 to 57 percent
      objectively cured or improved, the reported morbidity in these procedures is
      minimal; repeated injections can improve the outcome. The experience with
      autologous fat and silicone microimplants is insufficient, with an overall
      success rate of 70 percent (1-40 months follow-up; mean 12 months) and 58 to 70
      percent (17-36 months), respectively. Most of the procedures are performed as
      outpatient cases, and some under local anesthesia. These procedures are minimally
      invasive, usually safe and well tolerated, require shorter hospitalization, and
      are cost effective. In conclusion, in carefully selected patients, periurethral
      injection seems to be a reasonable option in the modern treatment of female
      stress incontinence.

PMID- 9618716
TI  - Ultrastructural identification of substance P containing nerves in the guinea pig
      trabecular meshwork.
AB  - We aimed to provide a detailed analysis of substance P (SP)-containing nerves in
      the trabecular meshwork by ultrastructural immunohistochemistry and capsaicin
      treatment for chemical ablation of the sensory nerves. Numerous myelinated and
      unmyelinated nerves were observed inside the sheets and intertrabecular spaces of
      the trabecular meshwork, and the inner side of Schlemm's canal. SP-like
      immunoreactive products were identified in some of these nerves and associated
      with numerous vesicles of different sizes, a few mitochondria and numerous
      neurotubili. After the capsaicin treatment, SP-like immunoreactive nerves
      persisted and no degenerated SP-like immunoreactive nerves were noted. On the
      basis of the ultrastructural features and the results of capsaicin treatment, it
      seems that these nerves are most probably autonomic in origin. Autonomic efferent
      SP-containing nerves are confirmed directly located in the trabecular meshwork;
      these have not been previously described at electron microscopic level. SP in
      autonomic efferent nerves might act as a neurotransmitter or neuromodulator for
      intraocular pressure regulation.

PMID- 9618717
TI  - Nilvadipine inhibits acute rise of aqueous flare and intraocular pressure induced
      by prostaglandin E2 in pigmented rabbits.
AB  - To evaluate the possible role of calcium channel blocker on changes in aqueous
      flare and intraocular pressure induced by prostaglandin E2 (PGE2) in pigmented
      rabbits, we examined the effects of nilvadipine and nicardipine (calcium channel
      blockers). PGE2, 25 micrograms/ml, was administered using a glass cylinder.
      Nilvadipine or nicardipine was injected intravenously. Aqueous flare was measured
      by a laser flare cell meter. Intraocular pressure was measured by a noncontact
      tonometer. After administration of PGE2, aqueous flare and intraocular pressure
      increased and then decreased. Increased flare and elevated intraocular pressure
      following PGE2 administration were inhibited by nilvadipine in a dose-dependent
      manner (5-500 micrograms/kg body weight). These responses were inhibited only
      slightly by nicardipine at the same concentration. Nilvadipine injected 30 min
      before PGE2 application inhibited the increase maximally. The inhibitory effect
      was found on days 1, 3, 5, and 7 by daily administration of nilvadipine. A good
      correlation between the inhibition of intraocular pressure and the inhibition of
      increased flare by nilvadipine was found. We believe that Ca2+, or calcium
      channel blocker-related substances may be involved in the mechanism of PGE2
      induced elevation of aqueous flare and intraocular pressure in the pigmented
      rabbit.

PMID- 9618718
TI  - Investigation of the 'fines' hypothesis of primary open-angle glaucoma: the
      possible role of alpha-crystallin.
AB  - Primary open-angle glaucoma is a disease caused by an increase in intraocular
      pressure due to a decreased facility of outflow of aqueous humor through the
      trabecular meshwork. The etiology of primary open-angle glaucoma is currently
      unknown, but it has been suggested that one possible mechanism may be the
      obstruction of flow through the trabecular meshwork by small macromolecules,
      analogous to the effect of 'fines' in column chromatography. One such candidate
      is alpha-crystallin, a lens protein which may be released into the aqueous humor
      from lens fiber cells at concentrations below that necessary for the formation of
      the native aggregate. Results of in vitro binding experiments indicate that alpha
      crystallin and serum albumin, which is secreted at the anterior root of the iris
      and is believed to act as a protein escort through the trabecular meshwork in
      mammalian eyes, will interact at concentrations of alpha-crystallin up to the
      critical micelle concentration for alpha-crystallin (3.5-5 mg/ml, or 0.18-0.25
      mM). There is little interaction at or above this concentration. This binding
      could serve the necessary function of preventing interactions between alpha
      crystallin monomers or small aggregates and hydrophobic surfaces within the
      trabecular meshwork. Since, however, the interaction between the two proteins is
      not extremely strong, the accumulation of unbound alpha-crystallin monomers
      and/or dimers could contribute to the development of primary open-angle glaucoma.

PMID- 9618719
TI  - Calcium-dependent proteolysis in rabbit lens epithelium after oxidative stress.
AB  - The purpose of this study was to examine changes in calcium-dependent proteolytic
      activity in the lens epithelium from whole rabbit lenses exposed to long-term
      oxidative stress at near physiological levels. Rabbit lenses, incubated in 50
      microM H2O2 for 1 or 24 h, were checked for clarity and morphological changes in
      the epithelium. Proteolytic activity was measured in the epithelium using a
      fluorogenic synthetic substrate; N-succinyl-Leu-Tyr-7-amino-4-methylocoumarin,
      both in the presence and the absence of calcium (1 mM Ca2+ and 5 mM EDTA
      respectively). The effect on transparency and morphology of the epithelium
      following a 1-hour incubation in 100 microM H2O2 was also studied. Lenses
      incubated in 50 microM H2O2 were clear even after 24h. After a 1-hour incubation
      in 50 microM H2O2 the epithelium of the exposed lens appeared normal. However,
      after 24 h the epithelium cells appeared swollen and microscopical examination
      showed extensive intracellular and subepithelial vacuolization. Incubation in 100
      microM H2O2 for 1 h caused loss of transparency; vacuole formation, globulization
      of the superficial lens fibers and death of the epithelial cells. There was a 55%
      increase in calcium-dependent proteolytic activity after 1 h in 50 microM H2O2,
      implying a role for the calcium-activated protease calpain in oxidatively induced
      cataract.

PMID- 9618720
TI  - Retinal cytokine response in mouse alkali-burned eye.
AB  - The kinetics of inflammatory cytokines in sensory retina of mice with corneal
      alkali-burned eyes were examined. Retinal samples were collected from ICR mice
      with unburned and alkali-burned eyes from day 3 to day 14. Enzyme-linked
      immunosorbent assay was used to quantitate the expression levels of interleukin-1
      alpha (IL-1 alpha), IL-1 beta and IL-6. Concentrations of IL-1 beta and IL-6 were
      significantly elevated at day 3 after alkali burn, and reduced to normal level by
      day 7. The concentration of IL-1 alpha was below assay sensitivity at all times.
      A significant elevation of IL-1 beta and IL-6 in the sensory retina may
      contribute to the retinal inflammatory response in the alkali-burned eyes. This
      is the first report suggesting that the retina is involved in the damage process
      of alkali burn.

PMID- 9618721
TI  - A morphological and morphometrical study of the retina in aging SAM mice.
AB  - We investigated whether neuronal cell loss occurred as a part of normal aging of
      the retina in the Senescence-Accelerated Mouse, strains SAMP1 and SAMR1, and in
      the BALB/c mouse. All three strains showed age-related atrophy of the retina
      after histologically normal development. Morphometrical study revealed the
      following facts. The rate of loss of photoreceptor cells in the peripheral retina
      was greater than in the central retina in all three strains. In the central
      retina, the rate of loss of photoreceptor cells was greater in the SAMP1 and
      SAMR1 mice than in the BALB/c mice. In the peripheral retinal, the SAMR1 and
      SAMP1 strains had fewer cells than the BALB/c strain at all ages, but the rate of
      loss of these cells did not differ among the three strains. The rate of loss of
      ganglion cells did not differ between the peripheral and central retinas in the
      three strains. The SAMR1 and SAMP1 strains had fewer ganglion cells in the
      peripheral retina than the BALB/c strain at all ages. Because the rate of age
      related loss of these cells in SAMP1 mice was not accelerated, and they were
      short-lived, SAMP1 mice did not show marked age-related loss. On the contrary,
      the SAMR1 mice showed a marked loss of photoreceptor cells and ganglion cells
      late in life because of their longer life span, and we propose that this strain
      is a suitable animal model for the study of mechanisms of age-related loss of
      neuronal cells in the retina.

PMID- 9618722
TI  - Antiuveitis and inhibition of fibroblast-like corneal and conjunctival cell
      cultures by interleukin-1 blockers, CK 125, CK 126 and CK 128.
AB  - Three new interleukin-1 (IL-1) blockers, CK 125, CK 126 and CK 128, were studied
      for their effects on IL-1-induced uveitis in rat eyes. They were more potent (at
      3-10 mg/kg t.i.d.) than prednisolone (20 mg/kg t.i.d.) in effectively inhibiting
      posterior uveitis. They were also found to inhibit fibroblast-like corneal cells
      at 10-300 micrograms/ml concentrations and conjunctival cells at 1-30
      micrograms/ml levels. The incorporation of leucine into corneal and conjunctival
      cells was either stimulated or unaffected by CK 126, indicating that the
      inhibition of cell growth has nothing to do with the protein synthesis. However,
      the incorporation of uridine into corneal and conjunctival cells was markedly
      inhibited by CK 126 at 3-30 micrograms/ml concentrations whereas the
      incorporation of thymidine into the cells was inhibited at a lesser extent than
      that of uridine. These results indicate that cell inhibition by CK 126 could be
      related mainly to the synthesis of mRNA and, to a lesser extent, to DNA
      synthesis.

PMID- 9618723
TI  - Secretion of cytokines by human choroidal melanoma cells and skin melanoma cell
      lines in vitro.
AB  - The selective secretion of interleukin 6 (IL-6), interleukin 8 (IL-8),
      interleukin 10 (IL-10), basic fibroblast growth factor (b-FGF) and transforming
      growth factor beta 1 (TGF beta-1) in tissue culture of choroidal melanomas and
      two established skin melanoma cell lines was investigated with ELISA analysis.
      Values of choroidal melanoma cells were compared with the melanoma cell lines and
      human fibroblasts as a physiological control. High secretion of IL-6 was
      detectable in choroidal melanoma cultures but not in the cell lines. IL-8
      secretion was found in all melanoma cultures. However, IL-10 was only secreted by
      one skin melanoma cell line and in choroidal melanoma cell cultures. B-FGF
      secretion by choroidal melanomas was higher than by cell lines. No differences
      were seen in the amounts of TGF beta-1 produced by melanoma cells. Human
      fibroblasts produce higher amounts of IL-6 and IL-8 but lower of b-FGF in vitro
      in contrast to the melanoma cells. The secretion of cytokines by choroidal
      melanoma cells suggests an important role of these soluble factors in the
      interaction of tumour and healthy tissue.

PMID- 9618724
TI  - The subretinal microphotodiode array retinal prosthesis.

PMID- 9618725
TI  - Specificity of predominant IgG4 antibodies to adult and microfilarial stages of
      Brugia malayi.
AB  - Human infections with filarial nematodes such as Brugia malayi are accompanied by
      unusually high titres of parasite-specific IgG4 antibodies. We have compared the
      profile of antigens recognised by filarial-specific IgG1 and IgG4 isotypes by
      Western blotting. Serum samples were collected from 120 subjects exposed to
      Brugia malayi, divided into three groups of asymptomatic amicrofilaraemic
      (endemic normal), microfilaraemic, and elephantiasis patients. Antigen
      preparations were tested from both adult B. malayi parasites, and from
      microfilariae; 24 distinct bands were analysed from the former, and 19 from the
      latter. Both qualitative scoring for band reactivity, and densitometric scanning
      of major bands, were employed. The consistent result was one of high and
      preferential IgG4 reactivity to a set of low molecular weight bands, of 15, 17,
      20, 31 and 33 kDa; most of the 19 other bands showed higher reactivity with IgG4.
      Analysis of Western blot patterns showed an overall tendency for stronger IgG4
      responses in microfilaraemic cases, and higher IgG1 responses in elephantiasis
      patients, consistent with published studies using ELISA on unfractionated
      parasite extracts. This study has defined an array of filarial antigens from each
      stage, and relative levels of IgG4 recognition, which will be important in
      unravelling distinct immune responses to this complex parasite.

PMID- 9618726
TI  - IgE responses in the serum and gastric lymph of sheep infected with Teladorsagia
      circumcincta.
AB  - The IgE response of naive or previously infected sheep to 50,000 infective larvae
      of Teladorsagia circumcincta was monitored in serum and gastric lymph using a
      monoclonal antibody generated to recombinant ovine IgE in a dot blot assay. In
      4/5 naive sheep, lymph and serum IgE concentrations increased from days 8 and 14
      after infection, respectively. In most previously infected sheep, the IgE
      response to challenge was more rapid, although not necessarily greater than that
      following a primary infection. IgE concentrations in lymph were some 4-fold
      higher than in serum indicating that its source was the mucosa or draining nodes.

PMID- 9618727
TI  - Suppressive effect of Ixodes ricinus salivary gland extract on mechanisms of
      natural immunity in vitro.
AB  - Tick saliva has been shown to contain a variety of pharmacologically active
      molecules, including those with immunosuppressive activities. There is increasing
      evidence that the nonspecific suppression of host immunity by tick saliva is
      exploited by tick-borne pathogens, e.g. the saliva-activated transmission (SAT)
      of some tick-borne viruses. We have demonstrated the suppressive effect of the
      salivary gland extract (SGE) derived from partially fed (five days) Ixodes
      ricinus females on important mechanisms of innate immunity: natural killer (NK)
      cells, interferon and nitric oxide production. SGE reduced the interferon
      induction by polyinosinic-polycytidylic acid (poly I:C) or Escherichia coli
      lipopolysaccharide (LPS) in a culture of Balb/c mouse splenocytes by 94% and 62%,
      respectively. SGE suppressed the cytotoxicity of nonstimulated and in vivo poly
      I:C-stimulated mouse NK cells by up to 31% and 26%, respectively. The induction
      of NK activity in vitro by LPS but not by Concanavalin-A (Con-A) was also
      downregulated in the presence of SGE. The addition of SGE to cultures of mouse
      macrophages partially inhibited the production of nitric oxide, induced by LPS.
      These data suggest that the facilitating effect of SGE on the transmission of
      some tick-borne pathogens might be associated with the suppression of the host
      innate resistance mechanisms, represented by interferon, nitric oxide and NK
      cells.

PMID- 9618728
TI  - Interferon production by Theileria annulata-transformed cell lines is restricted
      to the beta family.
AB  - Theileria are tick-transmitted protozoans causing often fatal diseases in
      ruminants. Theileria sporozoites immortalize and transform host cells of
      haematopoietic origin. Transformation is associated with profound functional
      alterations. For example, bovine cells infected by Theileria annulata or T.
      parva. constitutively produce interferon (IFN). In this study, the type and
      family of IFN produced by a panel of T. annulata-transformed cell lines and a T.
      parva-transformed cell line was investigated, using molecular probes specific for
      the members of the IFN-alpha, IFN-beta, IFN-gamma and IFN-omega family. T. parva
      transformed cells produced IFN-gamma exclusively, whereas T. annulata-infected
      cells expressed type I IFN only. Analysis of mRNA expression showed that this
      type I IFN was confined to IFN-beta, regardless of the cellular origin of the
      transformed cells. When cells were exposed to double-stranded RNA (poly (I:C))
      which induces IFN production in other systems, a 10-5,000 fold increase in IFN
      activity was noted. The amounts of IFN-beta mRNA were increased, but mRNA coding
      for IFN-alpha, IFN-omega or IFN-gamma was not detected. In contrast, primary
      macrophages, from which many of the tested lines were derived, expressed IFN
      alpha, IFN-beta and IFN-omega mRNA to similar degrees when stimulated by LPS or
      poly (I:C). Thus, T. annulata appears to constitutively turn on IFN-beta gene
      transcription while silencing the genes coding for IFN-alpha and IFN-omega.

PMID- 9618729
TI  - Mapping of B epitopes in GRA4, a dense granule antigen of Toxoplasma gondii and
      protection studies using recombinant proteins administered by the oral route.
AB  - GRA4, a dense granule protein of Toxoplasma gondii elicits both mucosal and
      systemic immune responses following oral infection of mice with cysts. We studied
      the antigenicity and immunogenicity of truncated and soluble forms of GRA4
      expressed as glutathione S-transferase fusion proteins in Escherichia coli.
      Protein C (amino-acids 297-345) was particularly well recognized by serum IgG
      antibodies, milk IgA antibodies and intestinal IgA antibodies from T. gondii
      infected mice and by serum IgG antibodies from T. gondii infected humans and T.
      gondii infected sheep. One major B epitope was localized within the last 11 C
      terminal residues of GRA4. A second epitope, recognized with lower frequency, was
      mapped within the region 318-334. In contrast, the N domain of GRA4 (amino acids
      25-276) was poorly recognized. Oral immunization of C57BL/6 mice with N, C or NC
      (amino acids 25-276 fused to 297-345) in association with cholera toxin induced a
      significant production of serum anti-GRA4 IgG antibodies but a weak and
      inconsistent intestinal anti-GRA4 IgG antibody response and afforded partial
      resistance to oral infection with T. gondii. These results provide new molecular
      and immunological understanding of GRA4 and indicate that it is a potential
      candidate for oral vaccination against T. gondii.

PMID- 9618730
TI  - Influence of the HLA class II polymorphism in chronic Chagas' disease.
AB  - Chagas' disease or American trypanosomiasis due to Trypanosoma cruzi has existed
      at least since the time of the Inca empire and contributes significantly to
      cardiovascular morbidity and mortality in several countries of this continent.
      Due to the fundamental role of human class II molecules polymorphic residues in
      the control of the immune response, a study was designed to define by DNA typing
      HLA class II alleles in a sample of 67 serologically positive individuals with
      and without cardiomyopathy and in 156 healthy controls of similar ethnic origin.
      Genomic DNA extraction, PCR amplification of the HLA-DRB1 and DQB1 second exon
      regions and hybridization to labelled specific probes were carried out following
      the 11th International Histocompatibility Workshop reference protocol. Comparison
      of DRB1 and DQB1 allele frequencies among the patients and control subjects
      showed a decreased frequency of DRB1*14 and DQB1*0303 in the patients, suggesting
      independent protective effects to the chronic infection in this population.
      Allele frequencies comparison between patients with and without cardiomyopathy
      showed a higher frequency of DRB1*01, DRB1*08 and DQB1*0501 and a decreased
      frequency of DRB1*1501 in the patients with arrhythmia and congestive heart
      failure. The results suggest that HLA Class II genes may be associated with the
      development of a chronic infection and with heart damage in Chagas' disease.

PMID- 9618731
TI  - Should we aim at tissue renin-angiotensin systems?
AB  - Recent developments in our knowledge of the renin-angiotensin system (RAS)
      necessitate an update of the classical view on this system. These developments
      pertain to the pathways leading to formation of angiotensin II and other active
      metabolites, their receptors, biological functions and the presence of renin
      angiotensin systems in tissues. The implications of the above new developments
      for the current interest in tissue renin-angiotensin systems as potential targets
      for drug therapy in cardiovascular disease are discussed in this review.

PMID- 9618732
TI  - Recent developments in the management of psychosis.
AB  - Antipsychotic drugs are effective in psychoses, whatever the aetiology of the
      disorder. The positive symptoms tend to respond more readily. The need for
      developing new drugs arises from the refractoriness of the negative symptoms, the
      10-25% of the patients that are treatment-resistant and the problems of short-,
      and long-term extrapyramidal side-effects. Thus far, five drugs differing from
      the classical antipsychotics have been licensed for use: clozapine, olanzepine,
      risperidone, sertindole and sulpiride, and in at least some European countries
      quetiapine is now in the final phase of clinical research. This review starts
      with a brief introduction to symptomatology, is limited to the registered drugs
      and addresses differences with the classical drugs in pharmacology,
      pharmacokinetics, clinical aspects and side-effects. Clozapine, risperidone and
      sulpiride can be considered for clinical use in refractory patients, and these
      three together with olanzapine and sertindole are candidates when extrapyramidal
      side-effects cause a clinical problem.

PMID- 9618733
TI  - Pricing and reimbursement of pharmaceuticals. A new culture for the community
      pharmacist.
AB  - Pricing and reimbursement of pharmaceuticals are of concern for pharmacists.
      Different countries have different ways of organising their health care systems.
      The place for pharmaceuticals within these systems also differ. This article
      looks into the price- and reimbursement systems for medicinal products in
      Germany, Sweden, the UK and Norway. Various ways of organising the pharmaceutical
      market emerge. Some existing measures have been in place for a long time while
      others have been introduced more recently. A common goal for the four countries
      seems to be the drive to cut costs, and attempts to do this can be directed
      through various reimbursement systems, by focusing on prices or by influencing
      the physicians' prescribing behaviour, either through the use of advice or
      through the use of budgets. It is important for the pharmacists to have in-depth
      knowledge of the price- and reimbursement system they have to work within in
      order to be of full service to their customers.

PMID- 9618734
TI  - Crossover studies are a better format for comparing equivalent treatments than
      parallel-group studies.
AB  - BACKGROUND: In controlled clinical trials the new treatment may be a slight
      modification of the standard or be equivalent to it with the addition of a new
      component. In this situation there is a positive correlation between the response
      to the new and the standard treatment. OBJECTIVE: The influence of the
      correlation between the treatment responses on the statistical sensitivity of
      testing was studied. Randomized trials of equivalent treatments in psychiatry and
      hypertension research were studied for their design in relation to their level of
      correlation. RESULTS: With equivalent treatments and, thus, a positive
      correlation a paired analysis provides better power than an unpaired one.
      CONCLUSIONS: Crossover studies are a better format than parallel-group studies
      for comparing equivalent treatments. The scientific community is technically
      largely unaware of the mechanisms by which correlation levels influence or lack
      to influence the statistical power of controlled clinical trials.

PMID- 9618735
TI  - Pharmacokinetics of quinine in African patients with acute falciparum malaria.
AB  - The pharmacokinetics of quinine were studied in six Nigerian patients during
      acute uncomplicated falciparum malaria and convalescent periods. An oral dose of
      10 mg/kg quinine dihydrochloride administered 8-hourly for 7 days gave parasite
      and fever clearance times of 36.0 +/- 16.6 h and 18.0 +/- 6.4 h, respectively.
      From the individual quinine plasma profiles the mean plasma concentration of
      quinine at the time of parasite clearance was estimated as 4.5 +/- 1.1
      micrograms/ml. Plasma quinine levels during malaria rose rapidly reaching a peak
      around the second and third days and declining thereafter as patients improved
      clinically. In acute malaria plasma quinine levels were more than two-fold higher
      than in convalescence; the mean AUC(0-12) in malaria was 37.9 +/- 14.7
      micrograms.h/ml compared to 17.9 +/- 8.5 micrograms.h/ml in convalescence. The
      apparent oral clearance (CL/F) and volume of distribution (Vd/F) during the acute
      phase of the malaria (1.9 +/- 0.7 ml/min/kg and 1.8 +/- 0.9 l/kg, respectively)
      were significantly lower than in convalescence (4.5 +/- 2.1 ml/min/kg and 4.2 +/-
      3.2 l/kg). The present data suggest that malaria parasites in African patients
      are still very sensitive to quinine and that the current dosage of quinine is
      effective for the treatment of acute falciparum malaria in African patients
      without augmenting therapy with any other drug such as tetracycline or
      sulphadoxine-pyrimethamine. It also confirms that malaria significantly alters
      the pharmacokinetics of quinine in humans.

PMID- 9618736
TI  - Genotyping of the arylamine N-acetyltransferase polymorphism in the prediction of
      idiosyncratic reactions to trimethoprim-sulfamethoxazole in infants.
AB  - The pathogenesis of hypersensitivity to trimethoprim-sulfamethoxazole (TMP-SMX)
      is supposed to be associated with the slow acetylation phenotype. This
      pharmacogenetic defect is associated with the mutations of the arylamine N
      acetyltransferase (NAT2) encoding gene. The aim of the study was to compare the
      usefulness of the acetylation phenotype and NAT2 coding genotype in the
      prediction of idiosyncratic reaction to Cotrimoxazole in infants. The study was
      carried out in the group of 20 infants, aged 2-12 months (mean age 6.3 months)
      treated with Cotrimoxazole, administered at 100 mg/kg b.w./24 h doses. In seven
      children (35%) no adverse effects of the treatment have been observed, whereas in
      13 (65%) children various adverse effects occurred as a result of the therapy,
      such as rash (4 children), granulocytopenia with anemization (5 children) or
      liver impairment (4 children). The acetylation phenotype of each child was
      determined on the basis of urine of N-acetyl isoniazid/isoniazid ratio, after
      ingestion of isoniazid as a model drug. Furthermore we used polymerase chain
      reaction (PCR) followed by the analysis of restriction fragments length
      polymorphism (RFLP) technique to identify the known mutant alleles of the NAT2
      gene. It has been presumed that the genotype determining fast acetylation
      contains at least one of wild-type allele. No correlation has been found between
      the observed adverse effects of Cotrimoxazole and age, gender and acetylation
      phenotype. However, it has been demonstrated that the risk of adverse effects of
      Cotrimoxazole is considerably higher in children with mutations of the NAT2
      encoding gene. The comparison of the results from PCR-RFLP genotyping with
      phenotyping suggested that in infants, the NAT2 genotype rather than phenotype
      provides the basis for the detection of hypersensitivity to TMP-SMX.

PMID- 9618737
TI  - European drug information centres--survey of activities.
AB  - A questionnaire survey of European drug information centres (DICs) was conducted.
      DICs mentioned in the ESCP directories and other sources were identified and
      contacted. Information on basic characteristics was obtained: affiliation, the
      scope of activities, employees, question-answer service characteristics,
      information sources and the economic aspects of the DICs' work. Information from
      84 DICs was analysed (return rate = 71.3%). DICs are mainly affiliated to
      hospitals (68%), rather rarely with faculties of pharmacy (6%) or with faculties
      of medicine (8.3%). Activities of DICs mainly include: question-answer service
      (98%), issue of bulletins (68%), participation in P&T committees (63%), tuition
      (61%) and drug-use evaluation (52%). Pharmacists, 1-2 full- or part-time, are the
      most frequent employees working in the DICs. When the question-answer service was
      analysed, it was found that 56% of the DICs are open only to the health-care
      professionals and 43% provide a service to the lay public. Questions are mainly
      concerned with the side effects, indication/therapeutic use and the dosage of the
      drugs. The majority of DICs (91%) document their activities, very often on a
      computer database. Quality assurance is provided by almost 75% of DICs, usually
      by a review (58%) or a feed-back questionnaire (32%). Information sources listed
      as most frequently used include Martindale--The Extrapharmacopeia, journals such
      as Lancet, Medline and Micromedex databases. DICs are usually financially
      supported by the organizations to whom they are affiliated. Fees are charged, for
      special activities, by 9.5% of DICs.

PMID- 9618738
TI  - Photosensitivity reaction to fluoxetine and alprazolam.
AB  - We report the case of a male individual who developed a severe photosensitive
      reaction after sun exposure during therapy with fluoxetin 20 mg bid plus
      alprazolam 0.25 mg bid due to depressive disturbances. The patients, of North
      African origin, was not taking other prescription medications nor over the
      counter products; in the past he had never shown any reaction to sunlight nor had
      ever used sun protective agents because of its phenotypical skin mark. Three
      months later, after a second photosensitive reaction, the pharmacological therapy
      was finally discontinued.

PMID- 9618739
TI  - Torsade de pointes after pipamperone intoxication.

PMID- 9618740
TI  - Individual and group antimicrobial usage rates on 34 farrow-to-finish swine farms
      in Ontario, Canada.
AB  - Antimicrobial drug-use was assessed on 34 farrow-to-finish operations that
      marketed at least 500 hogs/yr. These operations either did not use any
      antimicrobials or used narrow-spectrum or broad-spectrum antimicrobials in
      rations of post-weaning pigs. Total antimicrobial use was measured for two months
      after obtaining inventories and records of all antimicrobials used. The
      collection of empty medication bottles and inventories of drugs on hand was
      convenient for producers and useful for estimating or validating recorded
      treatment rates, particularly for antimicrobials that were used only in one class
      of pig. Treatment records, however, underestimated by approximately 35% the
      amounts used for 27/29 farm-antimicrobial combinations. Rates of individual-pig
      treatment varied from 0-24.1 pigs treated/1000 pig-days, with a median of 5.29.
      Most individual animal treatments were given to piglets and sows at parturition
      and penicillin was the most commonly used antimicrobial. Gentamicin was
      administered to suckling piglets on 19 of the farms.

PMID- 9618741
TI  - Prevalences of resistance to seven antimicrobials among fecal Escherichia coli of
      swine on thirty-four farrow-to-finish farms in Ontario, Canada.
AB  - Fecal specimens were composited and a hydrophobic-grid membrane-filter method was
      used to measure antimicrobial resistance to ampicillin 16 micrograms/ml, carbadox
      30 micrograms/ml, gentamicin 4 mu/ml, nitrofurantoin 32 micrograms/ml,
      spectinomycin 16 micrograms/ml, sulfisoxazole 32 micrograms/ml and tetracycline 8
      micrograms/ml among 8119 Escherichia coli isolates from 68 fecal samples
      collected on 34 farrow-to-finish swine farms marketing over 500 hogs/yr. The
      overall prevalences of resistance to antimicrobials among these isolates were:
      ampicillin 29%, carbadox 3.5%, gentamicin 0.6%, nitrofurantoin 27%, spectinomycin
      28%, sulfasoxizole 38% and tetracycline 71%. Thirty to seventy-six per cent of
      the variations in prevalences were explained by between-farm differences.

PMID- 9618742
TI  - Associations among antimicrobial drug treatments and antimicrobial resistance of
      fecal Escherichia coli of swine on 34 farrow-to-finish farms in Ontario, Canada.
AB  - Logistic regression was used to model associations between antimicrobial
      treatment and resistance among fecal Escherichia coli of finisher pigs at the
      farm level. Four sets of potential risk factors representing different levels of
      refinement of antimicrobial use on farms were modelled on resistance to
      antimicrobials. Final models for each antimicrobial were constructed from
      treatment and management variables significant on initial screening, and
      corrections for overdispersion were made. In general, in-feed antimicrobial
      treatment of pigs was more consistently associated with an increased risk of
      resistance than individual-animal treatment. Antimicrobial treatment in starter
      rations was significant in final models of resistance to ampicillin, carbadox,
      nitrofurantoin, sulfisoxizole, and tetracycline. Treatment in grower-finisher
      rations was significantly associated with resistance to ampicillin,
      spectinomycin, sulfisoxizole, and tetracycline. There was little evidence that in
      feed antimicrobials increased the risk of resistance to gentamicin, which is a
      drug used only for individual-pig treatment in this study population. These
      results suggest that antimicrobial medication of rations of post-weaning pigs
      selects for and maintains antimicrobial resistance among E. coli of finisher
      pigs. Although resistance was common on farms that did not medicate rations of
      post-weaning pigs, the results indicate that antimicrobial use does increase the
      risk of resistance to the antimicrobials studied.

PMID- 9618743
TI  - Cost analysis of immunisation against east coast fever on smallholder dairy farms
      in Kenya.
AB  - A spreadsheet model was developed and used to estimate the total cost of
      immunising cattle against East Coast fever (ECF) based on the infection-and
      treatment method. Using data from an immunisation trial carried out on 102 calves
      and yearlings on 64 farms in the Githunguri division, Kiambu district, Kenya, a
      reference base scenario of a mean herd of five animals, a 10% rate of reaction to
      immunisation and a 2-day interval monitoring regimen (a total of 10 farm visits)
      was simulated. Under these conditions, the mean cost of immunisation per animal
      was US$16.48 (Ksh 955.78); this was equivalent to US$82.39 (Ksh 4778.90) per five
      animal farm. A commonly reported reactor rate of 3% would decrease the cost of
      US$14.63 (Ksh 848.29) per animal. Reducing the number of farm monitoring visits
      from 10 to 7 would reduce the total cost by 10%, justified if farmers are trained
      to undertake some of the monitoring work. The fixed costs were 53% of the total
      cost of immunisation per farm. The cost of immunisation decreased with increasing
      number of animals per farm, showing economies of scale.

PMID- 9618744
TI  - Factors associated with seroprevalence to Mycobacterium paratuberculosis in small
      ruminant farms in the Madrid region (Spain).
AB  - A cross-sectional study was conducted in a population of small ruminants in the
      Madrid region (Spain) to determine the Mycobacterium paratuberculosis
      seroprevalence and to identify farm factors possibly associated with
      paratuberculosis (PTB). Farming-management information and sera were collected
      from 60 sheep or goat flocks. The relationship between seropositivity and the
      variables in the questionnaire was assessed by unconditional logistic regression,
      followed by random-effects logistic regression analysis to adjust for
      overdispersion between herds. The seroprevalence to M. paratuberculosis was 11.7%
      (64 out of 546) using agar-gel immunodiffusion assay (AGID). According to the
      sensitivity and specificity of the AGID test the true prevalence could be as high
      as 44%. A herd size of between 200-400 head and the presence of foreign breeds
      and their crosses were significantly associated with seropositivity (OR = 4.05
      and OR = 4.32, respectively). A higher replacement rate was also associated with
      seroprevalence to M. paratuberculosis (24.2% in positive herds vs. 18.1% in
      negative). All these three factors were related to more intensive management in
      the surveyed area. In contrast, membership of a professional livestock
      association appeared to be a protective factor against PTB (OR = 0.28). No
      variables related to veterinary assistance were associated with seroprevalence,
      probably reflecting the current lack of interest in PTB on the part of the animal
      health administration and veterinary services in Spain.

PMID- 9618745
TI  - Compensatory mechanisms in experimental and human parkinsonism: towards a dynamic
      approach.
AB  - This paper provides an overview of the compensatory mechanisms which come into
      action during experimental and human parkinsonism. The intrinsic properties of
      the dopaminergic neurones of the substantia nigra pars compacta (SNc) which
      degenerate during Parkinson's disease are described in detail. It is generally
      considered that the nigrostriatal pathway is principally responsible for the
      compensatory preservation of dopaminergic function. It is also becoming clear
      that the morphological characteristics of dopaminergic neurones and the dual
      character, synaptic and asynaptic, of striatal dopaminergic innervation engender
      two modes of transmission, wiring and volume, and that both these modes play a
      role in the preservation of dopaminergic function. The plasticity of the dopamine
      neurones, extrinsic or intrinsic to the striatum, can thus be regarded as another
      compensatory mechanism. Recent anatomical and electrophysiological studies have
      shown that the SNc receives both glutamatergic and cholinergic inputs. The
      dynamic role this innervation plays in compensatory mechanisms in the course of
      the disease is explained and discussed. Recent developments in the field of
      compensatory mechanisms speak for the urgence to develop a valid chronic model of
      Parkinson's disease, integrating all the clinical features, even resting tremor,
      and illustrating the gradual evolution of nigral degeneration observed in human
      Parkinson's disease. Only a dynamic approach to the physiopathological study of
      compensatory mechanisms in the basal ganglia will be capable of elucidating these
      complex questions.

PMID- 9618746
TI  - The neuronal machinery involved in successive orientation discrimination.
AB  - Following our strategy of using simple discrimination tasks to investigate the
      primate visual system, we trained both human and monkey subjects for two
      orientation discrimination tasks: an identification and a successive
      discrimination. Contrasting these two tasks allowed us to isolate the temporal
      comparison component and to relate this component to activity in right fusiform
      gyrus using Positron Emission Tomography (PET) and to infero-temporal cortex
      using a lesion approach in monkeys. Single-cell recordings in infero-temporal
      cortex demonstrated that neurons in this region can contribute to the three
      processes underlying temporal comparison: (1) sensorial representation of visual
      stimuli, (2) maintaining a trace of the preceding stimulus, and (3) comparison of
      the incoming stimulus with that trace. By the same token, a comparison of these
      two tasks, which use the same input and the same attribute, demonstrates the task
      dependency of processing in the human and non-human primate visual system.

PMID- 9618747
TI  - Recognition memory: neuronal substrates of the judgement of prior occurrence.
AB  - Recognition memory relies on two processes: (i) identification and (ii) judgement
      concerning prior occurrence. A system centred on perirhinal cortex appears to be
      responsible for judgement of prior occurrence based on discrimination of the
      familiarity of stimuli or their recency of occurrence; in contrast, a hippocampal
      system probably supplies information concerning the episodic, contextual aspects
      of recognition memory. This review chiefly concerns the perirhinal system and, in
      particular, neurones that signal the prior occurrence of stimuli by a decrease in
      response. Details concerning such decremental responses are given and it is
      argued that such responses in perirhinal cortex are adequate for and central to
      discrimination of stimulus familiarity and recency in a wide range of situations.
      Information is given of similar types of neuronal responses in anatomically
      related brain regions and what may be deduced about the operation of the
      recognition memory system. The possibility is discussed that the neuronal
      responses that signal information concerning the recent occurrence of stimuli may
      contribute to repetition priming as well as recognition memory. Other described
      changes in the activity of individual neurones such as response enhancements, or
      sustained (delay) activity may allow solution of specialised forms of recognition
      memory tasks where relatively short-term working memory is adequate. Implications
      of the multi-faceted nature of recognition memory for the interpretation of
      results are emphasised. Unsolved problems and avenues for future experimentation,
      including determining the nature of possible underlying synaptic plastic changes,
      are discussed.

PMID- 9618748
TI  - Cardiovascular and endocrine responses to experimental stress: effects of mental
      effort and controllability.
AB  - The objective of the study was to investigate the unique and interactive effects
      of the controllability of a task and mental effort required by that task on
      cardiovascular and endocrine reactivity, when both were manipulated
      independently. A 2 x 2 factorial design was used, with two levels of mental
      effort and two levels of control. Twenty-four healthy male subjects participated
      in each experimental condition. Heart rate, blood pressure, catecholamine and
      cortisol responses were determined. High effort lead to greater increases in
      heart rate, blood pressure and norepinephrine levels. Uncontrollability lead to
      higher cortisol, blood pressure and norepinephrine responses. In addition, there
      was an effort x control interaction effect on the diastolic blood pressure
      response. In conclusion, effort has clear sympathetic effects, whereas control
      influences both the sympathetic nervous system and the release of cortisol.
      Having control seems to be most beneficial in high effort situations, at least
      with respect to sympathetic reactivity.

PMID- 9618749
TI  - Prolonged and very intensive contact may not be conductive to menstrual
      synchrony.
AB  - Menstrual synchrony was not found for 30 cohabiting lesbian couples (mean time
      living together, 35 months), for whom 3 months of menstrual data were collected
      prospectively. A combined analysis with two previous studies of lesbian couples
      (Trevathan, W, Burleson, NH, Gregory, L (1993) No evidence for menstrual
      synchrony in lesbian couples. Psychoneuroendocrinology 18, 425-431; Weller, A,
      Weller, L (1992) Menstrual synchrony in female couples. Psychoneuroendocrinology
      17, 171-177) also failed to reveal synchrony. These data are considered together
      with a previous study of Bedouin couples which found only a moderate degree of
      synchrony (Weller, A, Weller, L (1997a) Menstrual synchrony under optimal
      conditions: Bedouin families. J Comp Psychol 111, 143-151). When women live
      together for an extensive period of time and have intensive social contact among
      them, the intensive contact may not be conducive to menstrual synchrony.

PMID- 9618750
TI  - Repeated blockade of mineralocorticoid receptors, but not of glucocorticoid
      receptors impairs food rewarded spatial learning.
AB  - Corticosteroids from the adrenal cortex influence a variety of behaviours
      including cognition, learning and memory. These hormones act via two
      intracellular receptors, the mineralo-corticoid receptor (MR) and the
      glucocorticoid receptor (GR). These two receptor types display a high
      concentration and distinct distribution in the hippocampus, a brain region which
      is directly involved in the regulation of spatial orientation and learning. In
      this study, repeated subcutaneous administration of the mineralocorticoid
      receptor antagonist RU28318 (1.0 mg/100 g body weight), the glucocorticoid
      receptor blocker RU38486 (2.5 mg/100 g body weight), or a combination of both
      antagonists were investigated for their effects on working--and reference memory
      in morning and afternoon trials during 8 subsequent days in food rewarded spatial
      learning in a hole board task. Each rat received one dose of either vehicle (2%
      ethanol in PEG 400), RU28318, RU38486 or the combination of both antagonists
      directly after the first trial on training days 1, 3, 5, and 7. The experiments
      demonstrated that repeated blockade of mineralocorticoid receptors impairs
      reference memory reflected in the morning--as well as in the afternoon trial,
      whereas blockade of glucocorticoid receptors has little effect on this type of
      cognitive behaviour. Furthermore, combined blockade of MRs and GRs resulted in a
      decrease, in both daily trials, in reference memory as well as working memory
      performance. These findings suggest that in this spatial learning paradigm, the
      impairment of working memory required blockade of both receptor types, while
      reference memory performance involves predominantly the mineralocorticoid
      receptors.

PMID- 9618751
TI  - Cognitive changes during growth hormone replacement in adult men.
AB  - The present study evaluates the effects of 2 years of growth hormone (GH)
      replacement therapy on psychological well-being and cognitive performance in
      adults with childhood-onset growth hormone deficiency (CO-GHD). A total of 48 GHD
      adult men (mean age: 27 years) were randomly assigned to one of four treatment
      groups: placebo treatment, or GH replacement in a dose of 1, 2, or 3 IU/m2,
      respectively. Placebo treatment was given for 6 months. Psychological assessments
      were made every 6 months. Assessments included somatic and psychological
      complaints, depression, fatigue, vigor, tension, state/trait anxiety, iconic
      memory, short-term memory, long-term memory and perceptual-motor skill. GH
      treatment was considered physiological if the observed insulin-like growth factor
      I (IGF-I) levels were within the normal range. It was considered
      supraphysiological if serum IGF-I rose to a value exceeding the upper normal
      limit. During the placebo-controlled phase of the study the changes in memory
      performance were positively correlated to the GH induced changes in serum IGF-I
      concentration and, more weakly, to the daily GH substitution dose. At 6 months
      memory only had improved in the group receiving supraphysiological GH treatment,
      but not in the group of patients who had a normalization of serum IGF-I. However,
      after 1 year of treatment a normalization of memory functioning was found in both
      groups of patients and this was preserved during the 2nd year of treatment. No
      changes were observed in psychological well-being and perceptual-motor skill. We
      conclude that GH replacement improves memory function in adults with CO-GHD. It
      has no effect on psychological well-being or perceptual-motor skill.
      Supraphysiological treatment accelerates the recovery of memory performance.
      However, the long-term effects are not different from those achieved with
      physiological GH replacement.

PMID- 9618752
TI  - Growth hormone replacement does not improve psychological well-being in adult
      hypopituitarism: a randomized crossover trial.
AB  - In order to examine the effect of growth hormone (GH) on psychological parameters
      in adult hypopituitarism, 20 adults were studied, mean age 47 years (range 20-69)
      with hypopituitarism and confirmed GH deficiency (GH < 3 micrograms/l following
      clonidine 0.15 mg/m2). Subjects were randomly allocated to either GH-up to 0.25
      U/kg per week in daily doses) or placebo for 3 months before crossover to the
      opposite treatment arm. Psychological parameters were assessed by self-reported
      questionnaires (Disease Specific Questionnaire (DSQ), the Symptom Checklist-90
      (SCL-90), and the Social Adjustment Scale (SAS)) at baseline and monthly
      intervals to the end of the trial. Both SAS and SCL-90 total scores showed a
      significant decline with respect to time (p = .03 and .013 respectively),
      although this was not a function of active treatment. DSQ showed a trend to
      decline (p = .06), but no effect of active treatment. None of the subscale
      components of the SCL-90 showed any significant change on active treatment.
      Improvement in psychological parameters occurs as a function of enrolment to a
      clinical trial, rather than active GH replacement in adult hypopituitarism.

PMID- 9618753
TI  - Glucocorticoid interactions with memory function in schizophrenia.
AB  - Glucocorticoid (GC) exposure can affect brain function, including potential
      adverse effects on hippocampal physiology and on specific elements of cognitive
      performance. In a prior study of healthy adult humans, decreased verbal memory
      performance was detected during four days of double-blind, placebo-controlled
      dexamethasone (DEX) treatment. Using an identical experimental design and sample
      size (n = 19), the cognitive effect of DEX treatment was studied in 11 subjects
      with schizophrenia, compared with 8 receiving placebo. In contrast to the effect
      in healthy adults, GC treatment with DEX at this dose (cumulative 3.5 mg) and
      duration did not decrease verbal memory performance or other measures of
      cognitive function in the patients with schizophrenia. When data from this
      experiment was compared with data from the previous study of healthy adults,
      covarying differences in baseline memory performance, a significant 3-way
      interaction was detected between subject group, treatment condition, and the
      repeated measurements of verbal memory performance across baseline, treatment and
      washout (F[3,87] = 4.84, p = .0066), suggesting differential cognitive effects of
      DEX in the patients versus the previously studied healthy subjects. Baseline
      plasma cortisol concentrations (0800 h) prior to DEX treatment were inversely
      correlated with baseline delayed (rs = -0.536, p = .03) verbal recall
      performance, supporting a previous report. The current results await replication
      using a larger sample size but provide preliminary evidence for an altered
      behavioral response to acute GC exposure in schizophrenic versus healthy
      subjects, and further evidence for a relationship between chronic changes in
      circulating cortisol and the memory impairments found in this disorder.

PMID- 9618754
TI  - Citalopram increases pregnanolone sensitivity in patients with premenstrual
      syndrome: an open trial.
AB  - We have investigated the ability of citalopram, a serotonin reuptake inhibitor,
      to alter the functional sensitivity to a neuroactive steroid during the late
      luteal phase in twelve women with premenstrual syndrome. Sensitivity to
      pregnanolone was assessed by comparing the effect of three increasing doses of
      intravenous pregnanolone on saccadic eye velocity (SEV) and self-rated sedation.
      Testings were performed in two consecutive menstrual cycles; without treatment
      and during citalopram treatment. During citalopram treatment, pregnanolone
      injections induced a significant SEV reduction compared to vehicle, whereas
      during the pre-treatment cycle there was no significant change in SEV response
      between vehicle and pregnanolone injections. Citalopram treatment did not alter
      the self-rated sedation response to pregnanolone compared to vehicle in either
      study cycle. These findings indicate that treatment with a selective serotonin
      reuptake inhibitor in the luteal phase increases the pregnanolone sensitivity in
      patients with premenstrual syndrome.

PMID- 9618755
TI  - Transcriptional regulation of blood formation during Xenopus development.
AB  - Hematopoiesis is the generation, proliferation and differentiation of
      hematopoietic stem cells (HSCs) into the erythroid, myeloid and lymphoid
      lineages. The HSC is a ventral mesodermal derivative that arises due to inductive
      and patterning processes triggered by bone morphogenetic protein 4 (BMP-4).
      Recent studies in Xenopus laevis have identified families of transcription
      factors that participate in hematopoietic development. Transcription factor
      families, such as the SMADs, Mixs and Vents pattern mesoderm to a ventral fate
      which ultimately results in the expression of hematopoietic-specific
      transcription factors such as GATA-1 and SCL. This transcriptional regulatory
      network enforces the correct temporal and spatial expression of the blood
      program.

PMID- 9618756
TI  - PU.1 and hematopoiesis: lessons learned from gene targeting experiments.
AB  - The advent of gene targeting technology in mouse embryonic stem cells has
      revolutionized the study of the development of organ systems in mammals.
      Hematopoietic transcription factors play a critical role in blood cell
      development. Targeted mutagenesis of the murine PU.1 locus has revealed the
      pivotal role this protein plays in blood cell differentiation at all stages of
      hematopoiesis (yolk sac, fetal liver and bone marrow). PU.1 has been disrupted by
      two independent research groups and both strains of PU.1-deficient mice exhibit
      abnormalities in B cell, T cell, monocyte and neutrophil development. The
      independent mutations have yielded some differences in phenotype suggesting that
      the different strategies for gene targeting have resulted in the beginning of an
      'allelic series' at the PU.1 locus. Both strains of PU.1-/- mice provide exciting
      reagents for future study of the role of this factor in blood lineage
      specification.

PMID- 9618757
TI  - Ikaros in hemopoietic lineage determination and homeostasis.
AB  - Studies on the molecular mechanisms that control hemopoietic differentiation have
      focused on signaling cascades and nuclear effectors that drive this complex
      developmental system in a regulated fashion. Here we review the role of Ikaros,
      the founding member of a unique family of zinc finger transcription factors in
      this developmental process. Studies on an Ikaros null mutation have revealed an
      essential role for this factor in lymphoid cell fate determination and at
      subsequent branch points of the T cell differentiation pathway. Differences in
      the phenotypes of a null and a dominant negative (DN) Ikaros mutation provide
      insight into a regulatory network through which Ikaros proteins exert their
      effects in development. In addition a comparative analysis of the hemopoietic
      stem cell and precursor compartment resulting from the two Ikaros mutations
      reveals a profound yet not absolute requirement for Ikaros in the production and
      differentiation of these populations.

PMID- 9618758
TI  - HMG box containing transcription factors in lymphocyte differentiation.
AB  - The identification of the mammalian sex-determining gene Sry has led to the
      discovery of a large family of related ('HMG box') transcription factors that
      control developmental events in yeast, C. elegans, Drosophila and vertebrates. In
      lymphocyte differentiation, several HMG box proteins play a decisive role. Sox-4
      is important for very early B-cell differentiation, while TCF-1/LEF-1 play a
      crucial role in early thymocyte development. TCF/LEF proteins have recently been
      found to constitute a downstream component of the Wingless/Wnt signal
      transduction pathway. In flies, this pathway controls segment polarity; in
      Xenopus it controls the definition of the body axis. Deregulation of the pathway
      occurs in several human tumors. These insights in the molecular events that are
      involved in TCF/LEF function in these organisms may eventually lead to the
      understanding of the function of these HMG box proteins in lymphoid development.

PMID- 9618759
TI  - Loss- and gain-of-function mutations reveal an important role of BSAP (Pax-5) at
      the start and end of B cell differentiation.
AB  - Pax-5 codes for the transcription factor BSAP which is expressed throughout B
      cell development except in terminally differentiated plasma cells. Gene targeting
      experiments in the mouse revealed a differential dependency of fetal and adult B
      lymphopoiesis on this transcription factor. BSAP is required for B-lineage
      commitment in the fetal liver and for progression beyond an early pro-B cell
      stage in adult bone marrow. The characterization of Pax-5-deficient pro-B cells
      demonstrated an important role of BSAP in the regulation of the CD19, mb-1 (Ig
      alpha) and N-myc genes as well as in the developmental pathway controlling VH-to
      DHJH recombination at the immunoglobulin heavy-chain (IgH) locus. The human PAX-5
      gene was recently shown to participate together with the IgH locus in the
      chromosomal translocation t(9;14)(p13;q32). This translocation is characteristic
      of a small subset of non-Hodgkin lymphomas exhibiting plasmacytoid
      differentiation. The translocated PAX-5 gene is deregulated by the insertion of
      IgH regulatory elements into its 5' region, which may contribute to tumorigenesis
      by interfering with the shut-down of PAX-5 transcription and thus with the
      completion of plasma cell differentiation.

PMID- 9618760
TI  - The role of E-proteins in B- and T-lymphocyte development.
AB  - Department of lymphocytes from hematopoietic stem cells is controlled, in part,
      by the activity of transcriptional regulatory proteins. In particular, one class
      of helix-loop-helix proteins, termed E-proteins, have been implicated in the
      regulation of gene expression during B-cell development. Recent analysis of gene
      targeted mice has allowed a direct assessment of the functional roles of several
      E-protein family members in hematopoiesis. In this review we describe the defects
      in B- and T-lymphocyte development in mice carrying targeted mutations in the E
      protein genes and discuss our current understanding of the role of these proteins
      in lymphoid development.

PMID- 9618761
TI  - Lymphoid-specific transcription mediated by the conserved octamer site: who is
      doing what?
AB  - The conserved octamer site found in the promoters of Immunoglobulin (Ig) genes
      has been identified early on as a key element for B cell-specific Ig promoter
      activity and has also been associated with expression of other B cell-specific
      genes. Several transcription factors--ubiquitous or cell-restricted--interact
      specifically with the octamer motif in B cells: Oct-1 and Oct-2 are POU domain
      transcription factors that bind directly to the octamer site and thereby can
      recruit the coactivator OBF-1 to the promoters of various genes. Yet, in spite of
      intense work, the precise role played by each of these factors for transcription
      activation through the octamer motif is unclear. In particular, genetic
      inactivation in mice of the lymphoid cell-specific transcription factor Oct-2 or
      of the B cell-specific coactivator OBF-1 led to surprising findings that are
      being discussed.

PMID- 9618762
TI  - Genetics and treatment of primary immunodeficiencies. Introduction.

PMID- 9618763
TI  - X-linked agammaglobulinemia: lack of mature B lineage cells caused by mutations
      in the Btk kinase.

PMID- 9618764
TI  - The hyper-IgM (HIM) syndrome.

PMID- 9618765
TI  - Severe combined immune deficiencies due to defects of the common gamma chain-JAK3
      signaling pathway.

PMID- 9618766
TI  - The molecular basis of chronic granulomatous disease.
AB  - CGD is a rare inherited immunodeficiency syndrome, caused by the phagocytes'
      inability to produce (sufficient) reactive oxygen metabolites. This dysfunction
      is due to a defect in the NADPH oxidase, the enzyme responsible for the
      production of superoxide. It is composed of several subunits, two of which,
      gp91phox and p22phox, form the membrane-bound cytochrome b558, while its three
      cytosolic components, p47phox, p67phox and p40phox, have to translocate to the
      membrane upon activation. This is a tightly and intricately controlled process
      that involves, among others, several low-molecular weight GTP-binding proteins.
      Gp91phox is encoded on the X-chromosome and p22phox, p47phox and p67phox on
      different autosomal chromosomes, and a defect in one of these components leads to
      CGD. This explains the variable mode of inheritance seen in this syndrome.
      Clinically CGD manifests itself typically already at a very young age with
      recurrent and serious infections, most often caused by catalase-positive
      pathogens. Modern treatment options, including prophylaxis with trimethoprim
      sulfamethoxazole and rIFN-gamma as well as early and aggressive anti-infection
      therapy, have improved the prognosis of this disease dramatically. CGD, as a very
      well-characterized inherited affection of the hematopoietic stem cells, is
      predestined to be among the first diseases to profit from the advances in cutting
      edge therapeutics, such as gene therapy and in utero stem cell transplantation.

PMID- 9618767
TI  - The Wiskott-Aldrich syndrome.

PMID- 9618768
TI  - Lymph node pathology in primary combined immunodeficiency diseases.

PMID- 9618769
TI  - Stem cell transplantation for immunodeficiency.

PMID- 9618770
TI  - Gene therapy of primary immunodeficiencies.

PMID- 9618771
TI  - Estimating the effect of zidovudine on Kaposi's sarcoma from observational data
      using a rank preserving structural failure-time model.
AB  - Researchers commonly express scepticism about using observational data to
      estimate the effect of a treatment on an outcome the treatment is intended to
      affect. In this paper, we consider using data from the Multicenter AIDS Cohort
      Study (MACS) to determine whether zidovudine prevents the development of Kaposi's
      sarcoma among HIV-positive gay men. Several methodologic issues common to
      observational data characterized the study: information on potentially important
      confounders was missing at some study visits; investigators did not always know
      the time of changes in treatment level, nor the value of confounders at that
      time, and the censoring process depended strongly on time-varying covariates
      related to outcome. We describe application to our data of Robins' paradigm for
      defining, modelling and estimating the effect of a time-varying treatment and
      show how to modify his approach to deal with the methodologic issues we have
      mentioned. Further, we demonstrate that relative risk regression is less well
      equipped to deal with these issues. We compare our results to the findings from
      randomized trials, and conclude that observational studies may sometimes be
      useful in evaluating the effect of treatment on an intended outcome.

PMID- 9618772
TI  - Cancer phase I clinical trials: efficient dose escalation with overdose control.
AB  - We describe an adaptive dose escalation scheme for use in cancer phase I clinical
      trials. The method is fully adaptive, makes use of all the information available
      at the time of each dose assignment, and directly addresses the ethical need to
      control the probability of overdosing. It is designed to approach the maximum
      tolerated dose as fast as possible subject to the constraint that the predicted
      proportion of patients who receive an overdose does not exceed a specified value.
      We conducted simulations to compare the proposed method with four up-and-down
      designs, two stochastic approximation methods, and with a variant of the
      continual reassessment method. The results showed the proposed method effective
      as a means to control the frequency of overdosing. Relative to the continual
      reassessment method, our scheme overdosed a smaller proportion of patients,
      exhibited fewer toxicities and estimated the maximum tolerated dose with
      comparable accuracy. When compared to the non-parametric schemes, our method
      treated fewer patients at either subtherapeutic or severely toxic dose levels,
      treated more patients at optimal dose levels and estimated the maximum tolerated
      dose with smaller average bias and mean squared error. Hence, the proposed method
      is promising alternative to currently used cancer phase I clinical trial designs.

PMID- 9618773
TI  - Optimal vaccine trial design when estimating vaccine efficacy for susceptibility
      and infectiousness from multiple populations.
AB  - Vaccination can have important indirect effects on the spread of an infectious
      agent by reducing the level of infectiousness of vaccinees who become infected.
      To estimate the effect of vaccination on infectiousness, one typically requires
      data on the contacts between susceptible and infected vaccinated and unvaccinated
      people. As an alternative, we propose a trial design that involves multiple
      independent and interchangeable populations. By varying the fraction of
      susceptible people vaccinated across populations, we obtain an estimate of the
      reduction infectiousness that depends only on incidence data from the vaccine and
      control groups of the multiple populations. One can also obtain from these data
      an estimate of the reduction of susceptibility to infection. We propose a
      vaccination strategy that is a trade-off between optimal estimation of vaccine
      efficacy for susceptibility and of vaccine efficacy for infectiousness. We show
      that the optimal choice depends on the anticipated efficacy of the vaccine as
      well as the basic reproduction number of the underlying infectious disease
      process. Smaller vaccination fractions appear desirable when vaccine efficacy is
      likely high and the basic reproduction number is not large. This strategy avoids
      the potential for too few infections to occur to estimate vaccine efficacy
      parameters reliably.

PMID- 9618774
TI  - Multi-level modelling of conception in artificial insemination by donor.
AB  - Data on insemination with donor's sperm have a crossed hierarchical structure due
      to the coexistence of female factors (ovulatory cycles within pregnancy attempt
      within women) and male factors (inseminations within donations within donors). A
      crossed random multi-level logistic model, taking account of this structure,
      permits an improved estimation of the fixed effects and provides insights into
      their influence at each level in the hierarchy. We present an efficient algorithm
      for fitting such models using alternating EM steps. We further discuss the
      inclusion of compositional covariates to determine what information the quality
      of a donation conveys regarding the donor basal fecundability and on the specific
      sperm donation.

PMID- 9618775
TI  - Sample size requirements for the comparison of two or more coefficients of inter
      observer agreement.
AB  - I provide sample size formulae and tables for the design of studies that compare
      two or more coefficients of inter-observer agreement or concordance. Such studies
      may arise, for example, when interest centres on assessment of how measures of
      inter-observer agreement vary across different patient subgroups or treatment
      centres. I consider cases of both a continuous and a dichotomous outcome measure.
      Three examples illustrate the results.

PMID- 9618776
TI  - Feed forward neural networks for the analysis of censored survival data: a
      partial logistic regression approach.
AB  - Flexible modelling in survival analysis can be useful both for exploratory and
      predictive purposes. Feed forward neural networks were recently considered for
      flexible non-linear modelling of censored survival data through the
      generalization of both discrete and continuous time models. We show that by
      treating the time interval as an input variable in a standard feed forward
      network with logistic activation and entropy error function, it is possible to
      estimate smoothed discrete hazards as conditional probabilities of failure. We
      considered an easily implementable approach with a fast selection criteria of the
      best configurations. Examples on data sets from two clinical trials are provided.
      The proposed artificial neural network (ANN) approach can be applied for the
      estimation of the functional relationships between covariates and time in
      survival data to improve model predictivity in the presence of complex prognostic
      relationships.

PMID- 9618777
TI  - Inborn errors of steroidogenesis.

PMID- 9618778
TI  - Role of transforming growth factor beta 1 (TGF beta 1) in mediating androgen
      induced growth inhibition in human adrenal cortex in vitro.
AB  - We have previously found that the androgen receptor gene is expressed both in
      normal and adenomatous human adrenal cortex and in the NCI-H295 human
      adrenocortical cancer cell line. Furthermore, we have observed that
      dihydrotestosterone (DHT) at physiological concentrations (10(-11) M) inhibits
      human adrenocortical cell growth in vitro and slightly decreases c-myc RNA levels
      in NCI-H295 cells. As c-myc is probably not the main mechanism mediating DHT
      induced inhibition of cell growth, other genes controlling cell proliferation may
      be involved. Transforming Growth Factor beta (TGF beta) is a regulatory peptide
      that acts by both autocrine and paracrine mechanisms to control proliferation and
      differentiation, and there is previous evidence that TGF beta may exert an
      antimitotic effect on human fetal adrenal cells in vitro. This study examines a
      possible role for TGF beta 1 in mediating the DHT-induced reduction of human
      adrenocortical cell growth. TGF beta 1 and its receptor (TGF beta RII) are
      expressed in DHT-treated and nontreated NCI-H295 cells; on Northern blot analysis
      24-h treatment with DHT (10(-11) M) produced a small increase in TGF beta RII
      RNA, and quantitative RT-PCR showed a 1.5-fold increase in TGF beta 1 RNA levels.
      These findings suggest that TGF beta 1 and its receptor may be involved in DHT
      induced inhibition of human adrenocortical cell growth.

PMID- 9618779
TI  - 5 alpha-reductase isozymes in the central nervous system.
AB  - The enzyme 5 alpha-reductase (5 alpha-R) activates several delta 4-3keto steroids
      to more potent derivatives which may also acquire new biological actions.
      Testosterone gives rise to the most potent natural androgen dihydrotestosterone
      (DHT), and progesterone to dihydroprogesterone (DHP), a precursor of the
      endogenous anxiolytic/anesthetic steroid tetrahydroprogesterone (THP). Two
      isoforms of 5 alpha-R, with a limited degree of homology, different biochemical
      properties and distinct tissue distribution have been cloned: 5 alpha-R type 1
      and type 2. In androgen-dependent structures DHT is almost exclusively formed by
      5 alpha-R type 2; 5 alpha-R type 1 is widely distributed in the body, with the
      highest levels in the liver, and may be involved in steroid catabolism. In the
      brain, the roles of the two isozymes are still largely unknown. This brief review
      will summarize recent experimental data from our laboratory which try to assign
      possible functional roles to the process of 5 alpha-reduction, and to the two 5
      alpha-R isoforms in the CNS.

PMID- 9618780
TI  - Neuroendocrine mechanisms underlying the control of gonadotropin secretion by
      steroids.
AB  - There is considerable evidence that although estradiol may trigger the
      preovulatory surge of gonadotropins, progesterone is required for its full
      magnitude and duration and that glucocorticoids bring about selective follicle
      stimulating hormone release. The luteinizing hormone-releasing hormone (LHRH)
      neuron does not have steroid receptors and is regulated by excitatory amino acid
      neurotransmission. Steroids do not appear to modulate excitatory amino acid
      receptors directly but increase release of glutamate in the preoptic area. This
      may be due to the suppression by steroids of the enzyme glutamatic acid
      decarboxylase67 that converts glutamate into GABA. NMDA receptors colocalize with
      nitric oxide synthase-containing neurons that surround the LHRH neurons in the
      preoptic area and intersect the LHRH fibers in the median eminence. Other
      potential novel pathways of LHRH release that are currently being explored
      include carbon monoxide generated by the action of heme oxygenase-2 on heme
      molecules and bradykinin acting via bradykinin B2 receptors.

PMID- 9618781
TI  - Effects and metabolism of steroid hormones in human neuroblastoma cells.
AB  - The development of the central nervous system is influenced by sex steroids and
      by their metabolites. However, little information on the possible effects of
      steroid hormones on neuroblastoma cells is available. Human neuroblastoma cell
      lines have been used as a model of human neuroblasts in vitro to study the
      metabolism of steroid hormones; in addition, the effects of steroids and steroid
      antagonists on neuroblastoma cell growth have also been investigated. The results
      obtained show that SH-SY5Y human neuroblastoma cells may actively metabolize
      testosterone and progesterone to their respective 5 alpha-reduced metabolites and
      that differentiation of neuroblastoma cells is paralleled by a significant
      increase in expression of the type-1 5 alpha-reductase and of the formation of
      steroid metabolites. All these data are suggestive of a potential role of steroid
      5 alpha-reduced metabolites in the biology of neuroblastoma cells. Studies
      performed to analyze the role of steroid hormones on neuroblastoma cell
      proliferation show that progesterone at low doses may induce minor stimulation,
      and at higher doses, a toxic effect on the neuroblastoma cell line SK-N-SH is
      seen. Moreover, the antiprogestin 17 beta-hydroxy-11 beta-(4-dimethylamino-phenyl
      1)-17-(prop-1-ynyl)estra-4,9-dien+ ++-3-one (RU486) decreases the proliferation
      of these cells in a dose-dependent manner. The effect of RU486 is not antagonized
      by either progesterone or dexamethasone, a result that seems to exclude the
      action of RU486 via classic intracellular steroid hormone receptors.

PMID- 9618782
TI  - Neuroblastoma and Alzheimer's disease brain cells contain aromatase activity.
AB  - Human brain steroidogenic mechanisms, particularly aromatase, have been
      investigated in healthy and diseased conditions. Aromatase activity was measured
      in differentiated and undifferentiated neuroblastoma cell lines from mouse (TMN)
      and human (5H SY5Y) and in human post mortem brain samples. Neuroblastomas show
      much higher aromatase activity than human brain samples. Homogenates of adult
      human male and female cortex and frontal and temporal areas of both Alzheimer's
      and control patients all show considerably lower activity. The temporal area has
      significantly higher aromatase activity than the frontal. Aromatisation activity
      in differentiated neuroblastoma cells of both species is lower than in
      undifferentiated cells. These results are consistent with an inverse relationship
      between brain estrogen formation and stage of neuronal differentiation and the
      hypothesis that aromatase may be involved in the early stages of neuronal growth.
      Significant but variable activities of other androgen-metabolising enzymes, such
      as 5 alpha-reductase, 3 alpha/beta-hydroxysteroid dehydrogenases, and 17 beta
      hydroxysteroid dehydrogenase, which generate a spectrum of regulatory molecules,
      are also found.

PMID- 9618783
TI  - Excitatory amino acid receptors and puberty.
AB  - Glutamate is an important excitatory signal in the hypothalamus for the steroid
      mediated preovulatory gonadotropin surge. Steroids may exert this action by
      regulating glutamate receptor levels or glutamate release, or both. Work in our
      laboratory found no changes in NMDA and kainate receptor binding in the
      hypothalamus of castrated or castrated plus steroid-replaced male and female
      rats. Likewise, we found that NMDA and kainate binding did not change over the
      onset of puberty in the female rat. A competitive quantitative RT-PCR assay using
      exogenous internal standards was used to measure NMDAR1, GluR1, and beta-actin
      mRNAs levels. NMDAR1 and GluR1 expression was examined in the preoptic
      hypothalamic area and in the medial basal hypothalamus at Postnatal Days 10, 15,
      20, 25, 30, 32, 34, 36, 40, and 63. A transient increase in GluR1 mRNA levels in
      the preoptic hypothalamic area was observed on Day 20, with all other time points
      showing comparable levels. NMDAR1 levels in the POA and medial basal hypothalamus
      did not change significantly at any of the time points; in contrast, however,
      AMPA receptor binding levels were increased in the hypothalamus at the time of
      puberty in the female rat. Thus, in addition to the previously reported elevation
      of glutamate release rates in the hypothalamus at the time of puberty, AMPA
      receptors may also be elevated and play a role in mediating glutamate regulatory
      effects on the timing of puberty in the female rat.

PMID- 9618784
TI  - Metabolism of synthetic corticosteroids by 11 beta-hydroxysteroid-dehydrogenases
      in man.
AB  - The presence of an 11 beta-hydroxyl group is essential for the anti-inflammatory
      and immunosuppressive effects of glucocorticoids. Interconversion of the 11 beta
      hydroxyl into the corresponding 11 beta-keto group and vice versa by 11 beta
      hydroxysteroid-dehydrogenase (11 beta-HSD) may thus play a pivotal role in the
      efficacy of these steroids. Therefore, we have compared the metabolism of the
      endogenous glucocorticoid cortisol (F) with that of synthetic 9 alpha-fluorinated
      steroids by 11 beta-HSDs in humans in vivo and in vitro. Whereas 30% of the free
      steroids in urine after oral administration of 5 mg of F is F itself and 70% the
      inactive keto-product cortisone (E), the urinary excretion of an identical dose
      of oral 9 alpha-fluorocortisol (9 alpha FF) is 90% 9 alpha FF and 10% inactive 9
      alpha-fluorocortisone (9 alpha FE). Kidney slices similarly convert F much faster
      to E than 9 alpha FF to 9 alpha FE; conversely, renal 11 beta-reduction of 9
      alpha FE to 9 alpha FF is much more effective than that of E to F. Kinetic
      analyses in human kidney cortex microsomes prove that the preference of
      fluorinated steroids for reduction in human kidney slices is catalyzed by 11 beta
      HSD type II: the NADH-dependent conversion of 11-dehydro-dexamethasone (DH-D),
      another fluorinated steroid, to dexamethasone (D) is very effective (high
      affinity, high Vmax), whereas reduction of E to F is very slow. In human liver
      microsomes (11 beta-HSD type I), nonfluorinated (E) and fluorinated 11
      dehydrosteroids (DH-D) are both reduced to their corresponding active 11
      hydroxyderivatives but with a Michaelis-Menten constant about 20-fold higher than
      for kidney microsomes (11 beta-HSD-II). Our results suggest that the decreased
      renal 11 beta-oxidation of 9 alpha-fluorinated steroids may offer pharmacokinetic
      advantages for renal immunosuppression. Furthermore, administration of
      fluorinated 11-dehydrosteroids is a new and exciting idea in glucocorticoid
      therapy in that small amounts of oral DH-D may pass the liver largely
      unmetabolized (11 beta-HSD-I has low affinity for such steroids) and may then be
      activated to D by high-affinity 11 beta-HSD-II, thus allowing selective
      immunosuppression in organs expressing 11 beta-HSD-II (kidney and colon).

PMID- 9618785
TI  - Androgens, estrogens, and second messengers.

PMID- 9618786
TI  - Control of the membrane sex hormone-binding globulin-receptor (SHBG-R) in MCF-7
      cells: effect of locally produced SHBG.
AB  - The interaction between plasma sex hormone-binding globulin (SHBG) and its
      receptor (SHBG-R) inhibits estradiol-induced proliferation of MCF-7 cells (human
      estrogen-dependent breast cancer) through cAMP and PKA. Thus, SHBG can modulate
      estradiol action in breast cancer, but the implications of this require a more
      detailed knowledge of the SHBG-R. To this end, we have transfected MCF-7 cells
      with an expression vector carrying the human SHBG cDNA (S-MCF-7) and studied the
      effects of this on both SHBG-R binding and cell proliferation. Control cells were
      parental MCF-7 (P-MCF-7) and MCF-7 cells transfected with the beta-galactosidase
      gene (B-MCF-7). Transfections were mediated by lipofectin followed by selection
      of transfected cells with G418. The amounts of SHBG in culture medium were
      evaluated by IRMA assay, with only S-MCF-7 cells shown to secrete SHBG; SHBG-R
      levels were evaluated by tracer binding technique. In P-MCF-7 and B-MCF-7 cells,
      SHBG-R was detectable as a two-binding site receptor, but no binding of SHBG was
      observed in S-MCF-7 cells. Proliferation of cells treated with estradiol was
      evaluated by [3H]thymidine incorporation in the three cell lines and in cells
      pretreated with SHBG (1 nM) purified from human serum or with conditioned medium
      from S-MCF-7 cells (medium S). In all three lines, cell proliferation increased
      after estradiol treatment. Preincubation with purified SHBG was effective in
      reducing estrogen-induced cell proliferation to basal levels in P-MCF-7 and B-MCF
      7 but not in S-MCF-7 cells. The estradiol effect was also inhibited in P-MCF-7
      cells treated with medium S. In conclusion, 1) SHBG inhibits estradiol-induced
      proliferation in cells containing a functional SHBG-R, whereas it has no
      detectable effect in cells in which the SHBG-R is either absent or not available
      to bind SHBG; and 2) S-MCF-7 cells are insensitive to SHBG (locally produced or
      exogenous) because their SHBG-R is occupied by SHBG.

PMID- 9618787
TI  - Establishment of a mouse Sertoli cell line producing rat androgen-binding protein
      (ABP).
AB  - The ultimate goal of this study was to compare the fate of rat testicular germ
      cells cocultured with mouse Sertoli cells that either do or do not produce rat
      androgen-binding protein (ABP). As a first step, we stably transfected a rat ABP
      expression construct into an immortalized mouse Sertoli cell line (TM4), which
      does not produce ABP when growing on plastic without hormones. The transfection
      of the pRc/CMV- rat ABP cDNA expression vector containing a neomycin resistance
      gene was made by either the liposome method (Dotap) or by polyethyleneimine
      transfection (PEI) into TM4 cell cultures. Neomycin-resistant clones were
      selected by adding Geneticin to the culture medium for 3 weeks. Analysis of over
      25 clones revealed the presence of recombinant rat ABP when cell extracts and
      culture media were probed with a rabbit polyclonal antibody raised against rat
      testicular ABP, indicating the translation and secretion of a protein similar to
      rat testicular ABP. Transfected TM4 cells maintain the secretion of rat ABP for
      more than 40 days, with immunopositive rat ABP localized within cytoplasmic
      granules in the Golgi region and along cytoplasmic processes in TM4 transfected
      with either vector. Electron microscopic study revealed a higher development of
      cytoplasmic organelles involved in protein secretion.

PMID- 9618788
TI  - Molecular pathophysiology and clinical manifestations of gonadotropin receptor
      defects.
AB  - The gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH)
      bind specific receptors, members of the G protein-coupled receptor superfamily.
      Mutations of gonadotropin receptors are classified into activating
      (constitutively active or gain-of-function mutations) and inactivating (loss-of
      function mutations). Activating mutations of the LH receptor have been described
      in familial and sporadic forms of male-limited pseudoprecocious puberty, whereas
      they do not appear to have any particular phenotype in females. The only
      activating mutation of the FSH receptor described to date was found in a
      hypophysectomized man who was fertile despite undetectable serum gonadotropin
      levels; the effects of constitutive FSH receptor activity in the context of
      normal pituitary function are not known. Homozygous inactivating mutations of the
      LH and FSH receptor invariably lead to amenorrhea in genotypical female subjects.
      In males, inactivation of the LH receptor in its more severe form results in a
      clinical picture similar to the syndrome of complete androgen resistance, but
      milder forms of hypoandrogenization have been described as well. In males,
      homozygous inactivation of the FSH receptor can also be associated with
      infertility. Finally, polymorphic variants of the FSH receptor are present in the
      normal population.

PMID- 9618789
TI  - Endothelin-1 is synthesized and biologically active in human epididymis via a
      paracrine mode of action.
AB  - In a previous study, we reported the presence of endothelin-1 and endothelin
      receptors in the human testis. We have now extended our investigations to the
      human epididymis. Since sperm appear to be immotile during their transit through
      the epididymis, it is conceivable that specific local factors promote smooth
      muscle contraction, enabling sperm transport. In this paper, we show that
      endothelin-1 mRNA and protein are readily detectable in the epithelial
      compartment of the human epididymis, and that endothelin converting enzyme- 1,
      which converts the precursor pro-endothelin-1 into active endothelin-1, is
      expressed in the epididymis, consistent with active processing of the prohormone.
      In addition, two classes of endothelin receptors were characterized and located
      in the muscle cells of the epididymis. These receptors correspond, in terms of
      affinity constants and capacity, to the previously characterized endothelinA and
      endothelinB receptor. These receptors appear to be biologically active and
      mediate the contractile activity of the epididymis in vitro. Our data suggest
      that endothelin-1, via a paracrine mode of action, may be responsible for sperm
      progression through this organ.

PMID- 9618790
TI  - Regulation of steroid production and its function within the corpus luteum.
AB  - During the second half of the luteal phase, the human corpus luteum becomes
      responsive to regular luteinizing hormone (LH) pulses. These LH pulses stimulate
      progesterone secretion tonically, and during this tonic stimulation, additional
      LH-independent progesterone pulses occur, which are particularly pronounced in
      women with human chorionic gonadotropin-stimulated luteal function. No
      progesterone pulses are seen in women suffering from corpus luteum deficiency due
      to absent LH pulses. The corpus luteum thus has a progesterone pulse generator
      turned on by gonadotropins but functioning for several hours without further
      gonadotropic support. This pulse generator appears to be regulated by intraluteal
      auto-/paracrine mechanisms, which we have investigated in a porcine model using
      molecular, cellular, and in vivo tools. Luteal oxytocin and progesterone release
      occurs in tightly coupled pulses. In vivo, oxytocin and prostaglandin F2
      alpha(PGF2 alpha) stimulate estradiol and progesterone release and estradiol
      itself further stimulates progesterone release. Analysis of the different luteal
      cell compartments (large luteal cells, small luteal cells, fibroblasts) suggests
      an intraluteal circuit that involves paracrine effects of estradiol, oxytocin,
      and PGF2 alpha. At the time of luteolysis, the luteotropic effects of estradiol
      are inhibited by tumor necrosis factor derived from invading macrophages and the
      intraluteal circuit is thereby disrupted, leading to luteolysis.

PMID- 9618791
TI  - Etiology of anovulation in polycystic ovary syndrome.
AB  - Various endocrine factors may contribute to the phenomenon of arrested follicular
      development, which is the hallmark of anovulatory infertility in polycystic ovary
      syndrome. Hypersecretion of luteinizing hormone and/or insulin, together with
      high intrafollicular concentrations of androgens, can interact to produce
      supraphysiological levels of cyclic AMP in granulosa cells, resulting in
      premature activation of terminal differentiation and, hence, arrest of follicle
      growth.

PMID- 9618792
TI  - Hyperandrogenism in the adolescent female.
AB  - Hirsutism in adolescent girls commonly starts as an esthetic problem in young
      women and is later complicated by the development of infertility and polycystic
      ovary syndrome, which are frequent consequences of prolonged hyperandrogenism. To
      ascertain whether particular prepubertal clinical manifestations may predict the
      development of adolescent hirsutism, we followed 70 girls with precocious
      pubarche (PP) with or without prepubertal hypertrichosis (PH) until 3 years (mean
      age 14.8 +/- 0.9 years) after menarche. Similar follow-up was carried out in six
      girls with PP secondary to 21 hydroxylase deficiency (NC-CAH), treated with
      hydrocortisone. In addition, a retrospective study on the incidence of precocious
      pubarche was performed in 139 hirsute teenagers (mean age 17 +/- 1.8 years).
      Testosterone, androstenedione, dehydroepiandrosterone sulphate, 17 alpha
      hydroxyprogesterone (basal and after ACTH), luteinizing hormone and follicle
      stimulating hormone were evaluated by radioimmunoassay or immunoradio metric
      assay in the early follicular phase, in cycling subjects. Pelvic ultrasonography
      was also performed. In the 139 hirsute teenagers, 29 had a history of PP (21% vs.
      0.6% in the general Italian population). Of these 139 patients, NC-CAH was
      diagnosed in 8 (6%), 5 of whom (63%) had PP. Of the 70 girls with PP, hirsutism
      was present in 44 (63%). PH was present in 37 of 44 patients (84%) with
      hirsutism, but only in 9 of 26 (35%) without hirsutism. Our results showed that
      1) PP represents a risk factor for the development of postpubertal hirsutism; 2)
      the association with PH seems to increase the risk probability; and 3) patients
      with hirsutism due to NC-CAH have a higher incidence of PP compared with other
      hirsute patients, but glucocorticoid treatment in such patients prevents the
      development of hirsutism. Whether early treatment in the other PP patients may
      prevent the development of hirsutism remains to be established.

PMID- 9618793
TI  - Steroid regulation during apoptosis of ovarian follicular cells.
AB  - In each estrous cycle, only one follicle, the dominant follicle, reaches full
      maturation while the other recruited follicles become atretic in a process
      characteristic of programmed cell death. Moreover, the old corpus luteum formed
      in a previous cycle undergoes luteolysis by a mechanism also characteristic of
      programmed cell death. Granulosa cells comprise the largest cell population of
      the ovarian follicle and are the main source of estradiol and progesterone in the
      ovary. Their cyclic nature of differentiation and death determines the cyclic
      secretion of female sex hormones and therefore serve as an excellent model for
      steroid regulation during apoptosis. The characteristics of granulosa cell
      apoptosis, as in other cell types, are cell membrane blebbing, DNA degradation
      and protease activation. In addition, there are specific characteristics of
      steroidogenic granulosa cell apoptosis, as follows: 1) The trigger for apoptosis
      may be exerted by different effectors and signal transduction mechanisms during
      follicle development. For example, tumor necrosis factor (TNF) may trigger
      granulosa cell apoptosis at early stage of follicular development, while cAMP/p53
      signals may trigger this process only in mature preovulatory granulosa cells. 2)
      cross-talk between paracrine and endocrine signals, and between death genes and
      tumor suppressor genes, may determine the fate of the granulosa cell. 3) in the
      mature follicle the follicular basement membrane plays an important role in
      transmitting survival signals and in prevention of apoptosis. 4) during the
      initial steps of apoptosis, steroidogenesis may be increased due to clustering of
      the steroidogenic organelles in the perinuclear region and their exclusion from
      the apoptotic blebs. 5) Actin cytoskeleton reorganization plays an important role
      in this compartmentalization as well as in transmitting survival signals exerted
      by basement membrane, laminin and growth factors which activate tyrosine kinase
      receptors.

PMID- 9618794
TI  - Concentration of sex steroids in adipose tissue after menopause.
AB  - Adipose tissue is a site of uptake, storage, action, and metabolism of sex
      steroids. After menopause aromatization of androgens to estrogens in adipose
      tissue is one of the most important sources of estrogen in the circulation and
      for peripheral tissues. The aim of this study was to estimate local sex steroid
      concentrations in breast and abdominal subcutaneous (s.c.) adipose tissue, to
      compare them with plasma concentrations and to investigate possible correlations
      with body mass index (BMI). The patients were postmenopausal women undergoing
      surgery for non-oncological reasons (Group A; n = 35) and breast cancer patients
      (group B; n = 19). The concentrations of estrone, 17 beta-estradiol, estrone
      sulfate, 17 beta-estradiol sulfate, androstenedione, androstenediol (androst-5
      ene-3 beta, 17 beta-diol), testosterone and dehydroepiandrosterone were measured.
      The method was based on frozen tissue homogenization, extraction with ethanol:
      acetone, delipidation, extraction of estrogens with ether, and of androgens with
      iso-octane in toluene, followed by RIA. The mean levels of steroids were higher
      in fat than in plasma, apart from testosterone. Levels of sulfates of estrogens
      and androstenediol were higher in breast than abdominal adipose tissue, and
      levels of estradiol lower. Positive correlations were found between BMI and
      tissue and plasma concentration of both estrone and androstenedione.

PMID- 9618795
TI  - DHEA and the intracrine formation of androgens and estrogens in peripheral target
      tissues: its role during aging.
AB  - Human and some other primates are unique since their adrenals secrete large
      amounts of dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S), which are
      converted into androstenedione (4-dione) and then into potent androgens and
      estrogens in peripheral tissues, therefore providing autonomous intracrine
      control to target tissues that can adjust the formation and metabolism of active
      sex steroids according to local requirements. Knowledge in this area has recently
      made rapid progress with the elucidation of the structure of most of the tissue
      specific cDNAs and genes that encode the steroidogenic enzymes responsible for
      the transformation of these inactive precursor steroids into androgens and/or
      estrogens. It is estimated that 30 to 50% of total androgens in men are
      synthesized in peripheral intracrine tissues from inactive adrenal precursors
      while, in women, peripheral estrogen formation is even more important, the best
      estimate being 75% before menopause and 100% after menopause. The marked
      reduction in the formation of DHEA-S by the adrenals during aging, especially
      before the age of 50 years, results in a dramatic fall in the formation of active
      sex steroids in peripheral target tissues, a situation which is thought to be
      associated with a long series of age-related decreases such as insulin
      resistance, obesity, osteoporosis, cardiovascular diseases, loss of muscle mass,
      cancer and other diseases. We have demonstrated for the first time a series of
      medically important beneficial effects of DHEA administered for 12 months to post
      menopausal women. Most interestingly, the bone mineral density significantly
      increased. This relatively rapid change was associated with an increase in plasma
      osteocalcin, a marker of bone formation, while a decrease in bone resorption
      reflected by a decrease in urinary hydroxyproline excretion was observed in
      parallel. In addition, the estrogenic stimulation of vaginal cytology in the
      absence of any sign of stimulatory effect on the endometrium is also of
      potentially major interest for the prevention and management of menopause.
      Furthermore, the inhibitory effect of DHEA on the growth of human breast cancer
      xenografts in vivo in nude mice supports the beneficial use of DHEA as hormone
      replacement therapy in women.

PMID- 9618796
TI  - Correlation between nuclear bodies and estrogen receptors in endometrial
      epithelial cells of old rats.
AB  - Nuclear bodies (NB) are prominent round structures in interchromatin regions of
      interphase nuclei, regarded as markers of stimulated rRNA synthesis. Their
      frequency was found to be estrogen-dependent and correlated with estrogen
      receptor (ER) content in endometrial epithelial cells of prepubertal and cyclic
      rats. The present study was designed to simultaneously examine the frequency of
      simple and complex NB and the status of ER in endometrial epithelia of old rats
      in relation to age and vaginal cytology. The vaginal cycles of old Wistar rats (n
      degree = 24) at 24, 28, 32, and 36 months of age, which were longitudinally
      monitored for at least 180 days by daily vaginal smears, were extremely irregular
      with a predominance of either persistent estrus or persistent diestrus over many
      days, weeks and even months. In all age groups ER-immunoexpression was very high
      (+3 = > 75%) in persistent-estrus rats and coincided with particularly frequent
      NB (2-3 simple NB out of 4-5 total NB per nuclear profile) in the tall epithelial
      cells with ultrastructural signs of intense protein synthesis. In persistent
      diestrus rats isolated simple and complex NB (1 per nuclear profile) and an
      almost absent ER expression were distinctive of the nuclei in low,
      ultrastructurally "inactive" endometrial luminal and glandular epithelial cells.
      Thus, ER immunoexpression and NB frequency are also estrogen-dependent in old
      rats. Our findings show, for the first time, that ER immunoexpression in
      endometrial epithelial cells is down-regulated only in old rats in persistent
      diestrus, whereas in persistent-estrus rats intense ER expression harmonizes with
      high NB frequency, irrespective of animal age.

PMID- 9618797
TI  - Estrogen receptor beta: re-evaluation of estrogen and antiestrogen signaling.
AB  - Estrogen is of vital importance for the development and control of reproductive
      functions. Until recently, estrogen was believed to regulate complex programs of
      gene expression by binding to an unique nuclear receptor belonging to the
      superfamily of ligand-dependent transcription factors. However, the
      identification of a second estrogen receptor, referred to as ER beta, is leading
      to a re-evaluation of estrogen signaling and physiology.

PMID- 9618798
TI  - Nonhypercalcemic analogs of vitamin D stimulate creatine kinase B activity in
      osteoblast-like ROS 17/2.8 cells and up-regulate their responsiveness to
      estrogens.
AB  - We have reported that pretreatment with 1 alpha, 25(OH)2D3(1, 25) up-regulates
      responsiveness and sensitivity to 17 beta estradiol (E2) in osteoblast-like
      cells, as measured by parallel stimulation of [3H]thymidine incorporation into
      DNA and the specific activity of creatine kinase BB (CK). Increased
      responsiveness was correlated with increased E2 receptor concentration. In this
      study, we have extended these observations to new nonhypercalcemic analogs of
      1,25. We compared the analogs hexafluoro vitamin D3 (FL), and the side chain
      modified derivatives: EB 1089 (EB), CB 1093 (CB) and MC 1288 (MC) with 1,25 and
      25 (OH)D3(25 D3). Treatment with 30 nM E2 for 4 h stimulated CK activity in ROS
      17/2-8 cells by 40%; there was no further increase after 3 daily additions of E2.
      Treatment by 3 daily additions, at 1 nM, of all analogs except 25 D3 caused a 2-3
      fold increase in CK specific activity. This schedule of treatment also
      upregulated the response to 4 h exposure to 30 nM E2 by 30-70% above the response
      to vitamin D analogs alone, and by up to 2 fold compared to E2 without
      pretreatment. At 1 pM, the analogs doubled CK activity, and, except for 1,25,
      upregulated the response to E2 to levels characteristic of each analog.
      Pretreatment with vitamin D analogs also increased the sensitivity to E2 by
      lowering the dose for a comparable response to E2 by one or two orders of
      magnitude. Stimulation of specific activity of CK by the analogs was paralleled
      by increases in the steady state level of mRNA for CKB, but not in its half life.
      Whereas pretreatment by vehicle followed by E2 for 2 h was unable to increase CKB
      mRNA, pretreatment with the analogs made possible detection of mRNA
      responsiveness to E2. These results add to the evidence for the interaction of
      estrogens and antiestrogens with vitamin D metabolites in regulation of bone
      growth in vitro. They also strengthen the potential for treatment of bone loss,
      as occurs in postmenopausal osteoporosis, by a combination of nonhypercalcemic
      vitamin D analogs and estrogens.

PMID- 9618799
TI  - Glucocorticoid-induced osteoporosis: prevention and treatment.
AB  - Glucocorticoid excess carries the risk of inducing secondary osteoporosis. In
      endogenous Cushing's syndrome, osteoporosis may be the presenting symptom of the
      underlying disease. Bone loss may reverse after the condition is cured, but often
      active treatment of established osteoporosis is necessary. In long-term
      glucocorticoid treatment at therapeutic doses, bone loss is likely and should be
      prevented; if prevention is ineffective, treatment is necessary. Hypercortisolism
      impairs calcium homeostasis and bone metabolism in a complex, multifactorial way:
      Glucocorticoids diminish calcium absorption and increase renal calcium excretion;
      this negative calcium balance leads to secondary hyperparathyroidism and
      osteoclast activation. Osteoblast activity is directly impaired by
      glucocorticoids, which lower activity of the gonadal hormone axis so that
      hypogonadism also contributes to bone loss. Glucocorticoids lead to muscle
      atrophy and decreased muscle strength with negative consequences for bone
      formation. For prevention and treatment, two different strategies have been used.
      The pathophysiological approach substitutes calcium and vitamin D in the first
      step; if bone loss nevertheless continues, bone formation is stimulated by
      fluorides. The alternative pharmaco-dynamic approach uses antiresorptives
      calcitonin or, for preference, bisphosphonates. Clinically it is mandatory to
      monitor all patients in whom glucocorticoids are used (e.g., organ transplant
      recipients) before and after the initiation of treatment to stabilize bone
      metabolism as early as possible.

PMID- 9618800
TI  - Interleukin 2 up-regulates glucocorticoid receptor number in human peripheral
      blood mononuclear cells and the osteosarcoma cell line Saos-2 in vitro.
AB  - Glucocorticoids are well-recognized modulators of immunocytes and osteoblasts via
      specific receptor-mediated mechanisms. We have evaluated the in vitro effect of
      interleukin 2 (IL-2) on the expression of glucocorticoid receptors (GRs) in
      peripheral blood mononuclear cells (PBMCs) obtained from healthy donors and
      osteoblast-like Saos-2 cells. Aliquots of PBMC or Saos-2 cells were incubated for
      20 h in the presence or absence of recombinant human IL-2 (100 IU/mL) at 37
      degrees C. After incubation, a [3H]dexamethasone radioligand-binding assay and
      Scatchard analysis were used to determine GR-binding parameters in both cell
      populations. Saos-2 cells basally express higher numbers of GR than PBMCs. After
      IL-2, a significant increase in GR number was found for both PBMCs and Saos-2
      cells. The relative increase was higher in Saos-2 cells; in PBMCs, the apparent
      affinity fell to almost half. These data represent an additional piece of
      evidence that cytokine and steroid hormones may act in a complementary way to
      regulate specific cell functions.

PMID- 9618801
TI  - Protein kinase C modulates estrogen receptors in differentiated osteoblastic
      cells in vitro.
AB  - Several reports have shown an interaction between the estrogen receptor (ER) and
      the protein kinase C (PKC) intracellular pathways. Data from our laboratory
      showed that PKC activation can modulate ER levels and responsiveness in estrogen
      target tissues such as uterus and bone. In particular, ROS.SMER #14 osteoblastic
      cells, stably transfected with the mouse ER, undergo specific morphological
      changes in vitro. ROS.SMER #14 cells at post-confluence express a differentiated
      phenotype and become unresponsive to estrogenic stimulation. Interestingly, ER
      mRNA and protein levels were not modified by post-confluence, but ER binding
      sites/cell (2500-3000/cell at subconfluence) were undetectable. Moreover, PKC
      activity was significantly increased in post-confluent cells. Inhibition of PKC
      by H7 or staurosporin (PKC inhibitors) or down-regulation by long-term treatment
      with 12-O-tetradecanoylphorbol-13-acetate enchanced ER binding capacity in a dose
      dependent manner. Since the PKC family includes several different isoforms that
      play different roles in cell homeostasis, we evaluated whether specific
      isoenzymes were involved in this event. To address this question, Western
      blotting analysis was performed on both sub- and post-confluent ROS.SMER #14
      cells using antibodies against different PKC isoforms. In conclusion, our
      preliminary data indicate that estrogen responsiveness of osteoblastic cells can
      be highly regulated by PKC. Finally, these data suggest that this intracellular
      interaction might play an important role in modulating hormonal and
      pharmacological responsiveness of bone tissue.

PMID- 9618802
TI  - 5 alpha-reductase inhibitors, chemical and clinical models.
AB  - An active site model of 5 alpha-reductase type 2 isoenzyme on an "active-analog
      approach" and based on 4-azasteroidal inhibitors has been constructed to evaluate
      the effects on the inhibitory potency of substituents on the steroid A ring. This
      model has proven able to predict the potential inhibitory activity of 19-nor-10
      azasteroid and 6-azasteroid compounds. A model for the evaluation of clinical
      efficacy of an inhibitor, based on in vitro data, has also been developed and
      applied to finasteride. This inhibitory potency evaluation of finasteride in
      human scalp homogenates, plus pharmacokinetic data, allows the calculation of a
      theoretical in situ inhibition value for human scalp. From the IC50 curve of
      finasteride in scalp homogenates, it is possible to calculate that for an
      inhibition level similar to that obtained in prostate with 5 mg of finasteride,
      the necessary plasma concentration of the drug is 1 microM, a level obtained
      after the acute administration of 50 mg of finasteride.

PMID- 9618803
TI  - Insulin-like growth factor-I and -II in human benign prostatic hyperplasia:
      relationship with binding proteins 2 and 3 and androgens.
AB  - In prostatic tissue, androgen action may be mediated by growth factors such as
      insulin-like growth factor-I (IGF-I) and II (IGF-II), which are mitogenic for
      prostatic cells and modulate the stroma-epithelium interaction. IGF-binding
      proteins (IGFBPs) have an autocrine and/or paracrine role in regulating the local
      actions of the IGFs. In this study, testosterone, dihydrotestosterone (DHT), 3
      alpha androstanediol (3 alpha diol), IGF-I, IGF-II, IGFBP2, and IGFBP3
      concentrations were evaluated in human benign prostatic hyperplasia (BPH) tissue.
      Samples of prostate tissue were removed by suprapubic prostatectomy from twelve
      BPH patients. Androgen tissue levels were determined by radioimmunoassay after
      purification on celite microcolumns. IGF-I, IGFBP2, and IGFBP3 were measured by
      radioimmunoassay, and IGF-II by immunoradio metric assay, after acidification and
      chromatography on Sep-pak C18 Cartridges for IGF-I and IGF-II. Androgen
      concentrations, expressed in ng/g tissue (mean +/- SE), were 0.51 +/- 0.05 for
      testosterone, 5.3 +/- 0.16 for DHT, and 1.1 +/- 0.07 for 3 alpha diol. IGF-I, IGF
      II, IGFBP2, and IGFBP3 levels were 24 +/- 3.7, 121 +/- 14 ng/g tissue and 0.44 +/
      0.05 and 1.2 +/- 0.17 micrograms/g tissue, respectively. No correlation between
      IGF-I, androgens, and IGFBPs was found. IGF-II was positively correlated with DHT
      (r = 0.78; p = 0.003) and 3 alpha diol (r = 0.66; p = 0.021) but not with IGFBPs.
      These data suggest that in BPH, DHT modulates the IGF system by increasing IGF-II
      without modifying IGFBPs. Therefore, the stroma-epithelium interaction, which
      plays an important role in prostatic growth, may be regulated by DHT through IGF
      II.

PMID- 9618804
TI  - Stimulated prostacyclin release by conduits used for coronary artery bypass
      grafting.
AB  - A direct comparison of the three coronary artery bypass conduits internal mammary
      artery (IMA), right gastroepiploic artery (RGEA), and saphenous vein (SV)
      concerning arachidonic acid (AA) stimulated release of the vasodilating and
      platelet inhibiting mediator prostacyclin was the aim of the present study.
      Pieces of saphenous vein (n = 16), right gastroepiploic artery (n = 8), and
      internal mammary artery (n = 19) were obtained from patients undergoing coronary
      artery bypass grafting. After a resting phase of 30 min in HEPES medium
      arachidonic acid (AA) was added in order to stimulate prostacyclin release. Time
      dependent production of the stable prostacyclin metabolite 6-keto-prostaglandin
      F1 alpha was determined following stimulation. Under basal conditions the IMA
      (12.4 ng/cm2) and RGEA (12.0 ng/cm2) released more prostacyclin than saphenous
      vein (4.0 ng/cm2). After AA stimulation 6-keto-prostaglandin F1 alpha release at
      30 min was as follows: IMA 806.0 ng/cm2, RGEA 35.9 ng/cm2, SV 82.3 ng/cm2 (p <
      0.0001 within grafts, p < 0.0001 between grafts, ANOVA for repeated measures).
      The internal mammary artery in comparison with the right gastroepiploic artery
      and saphenous vein seems to be better protected against local thrombotic events
      and development of coronary artery graft disease with the aid of the vasodilating
      and platelet inhibiting mediator prostacyclin.

PMID- 9618805
TI  - Pharmacologic heart rate reduction: effect of a novel, specific bradycardic agent
      on the heart.
AB  - Because heart rate (HR) is a major determinant of myocardial oxygen consumption
      (MVO2) a decrease in HR could prevent ischemia or reduce its consequences. We
      examined the effects of a novel bradycardic agent of the benzazepinone type, DK
      AH 269 (DK), on ventricular function and perfusion in 12 isolated, blood-perfused
      rabbit hearts. HR was significantly reduced by 1mumol/L DK (160 +/- 28 vs. 124 +/
      23 min-1); diastole lengthened from 235 +/- 69 to 334 +/- 85 ms. Aortic flow
      tended to fall after DK (50.0 +/- 29.6 vs. 35.6 +/- 21.5 ml/min), but stroke
      volume remained unchanged (0.29 +/- 0.16 vs. 0.28 +/- 0.17 ml) following DK. Peak
      left-ventricular pressure (LVPmax) (106 +/- 29 vs. 92 +/- 35 mmHg) and dp/dtmax
      (1482 +/- 582 vs. 1247 +/- 644 mmHg/s) were decreased. dp/dtmin, as a measure of
      early relaxation, was also decreased (-1361 +/- 362 vs, -1125 +/- 488 mmHg/s),
      whereas the end-diastolic pressure (LVPed) was increased (20 +/- 12 vs. 25 +/- 17
      mmHg). Coronary blood flow (CBF) per beat was not affected by DK: 0.07 +/- 0.02
      vs. 0.07 +/- 0.02 ml. However, the coronary resistance increased with DK from
      0.76 +/- 0.29 to 1.13 +/- 0.66 mmHg/(ml/min/100 g). The MVO2 was decreased (6.8
      +/- 3.4 vs. 5.9 +/- 2.8 ml/min/100 g). The relation between subendocardial and
      subepicardial flow (colored microspheres) was unchanged after DK (1.12 +/- 0.22
      vs. 1.13 +/- 0.16). Using electrical pacing to restore the control HR, dp/dtmax,
      LVPed, and MVO2 were nearly restored to predrug levels. In contrast, stroke
      volume, LVPmax, dp/dtmin and CBF per beat were less than control. In summary: DK
      effectively reduces heart rate and increases diastole. In parallel with the
      moderately reduced contractile function, MVO2 is reduced whereas CBF per beat is
      preserved. These results suggest that this novel bradycardic agent could be
      useful in treating unwanted tachycardia in the experimental setting,
      postoperative tachycardia in patients with heart disease or be useful even in
      treating coronary heart disease.

PMID- 9618806
TI  - Nitric oxide inhalation in acute pulmonary hypertension after cardiac surgery
      reduces oxygen concentration and improves mechanical ventilation but not
      mortality.
AB  - Impaired right-ventricular function may benefit from afterload reduction.
      Inhalation of nitric oxide (NO) reduces pulmonary hypertension without systemic
      circulatory depression. Influence of NO inhalation on oxygenation, ventilation,
      and hemodynamic parameters in 10 patients with acute pulmonary hypertension after
      cardiac surgery was examined in this study. Ten patients without NO treatment
      served as a control group. NO patients showed significantly improved oxygenation
      and recovery of right-ventricular function. Pulmonary artery pressure (12.8%),
      inspiratory oxygen demand (34.7%), PEEP (13.2%), and inspiration time (18.8%)
      decreased significantly during inhalation of nitric oxide. Mortality in both
      groups was identical. We therefore conclude that NO, by improving oxygenation and
      right-ventricular function, temporarily reduces invasiveness of mechanical
      ventilation. Reduction of invasiveness of ventilation did not influence mortality
      as compared with patients who did not receive NO. To finally estimate the benefit
      of NO inhalation, larger patient groups need to be examined.

PMID- 9618807
TI  - Transcatheter endomyocardial laser revascularization: a feasibility test.
AB  - By means of a special catheter system, a total of 76 endomyocardial laser
      channels were percutaneously produced in a controllable manner at selected sites
      in 6 beating canine hearts. Acute patency of channels (length = 4-11 mm, diameter
      = 0.5-1.2 mm) was documented angioscopically and histologically. This minimally
      invasive method might be useful for revascularising certain patients with
      ischemic heart disease without resorting to open-chest surgery.

PMID- 9618808
TI  - Pericardial substitution after cardiopulmonary bypass surgery: a trial of an
      absorbable patch.
AB  - Primary closure of the pericardium affords some protection against adhesion
      formation and the consequent hazards of resternotomy. However, its completion may
      be impractical and hazardous, and therefore the pursuit of an ideal pericardial
      substitute has prompted much research. Twenty calves were divided into 3 groups
      for the study. All animals underwent right posterolateral thoracotomy. The test
      group (group X), consisting of 6 animals, received a poly-beta-hydroxybutyrate
      patch (PHB) to close the pericardium following cardiopulmonary bypass (CPB). In
      group Y (9 animals) the pericardium was left open following CPB. Group Z (5
      animals) also had their pericardium left open but did not undergo CPB (non-CPB).
      The plasminogen activating activity (PAA) of homogenates of pericardial tissue
      samples were measured in 5 animals in group X, and 5 in group Z. Samples were
      taken at three time points from the time of pericardiotomy, and at reoperation 4
      weeks later. In group X (CPB) there was a significant reduction in the PAA during
      the operation with some recovery at reoperation. The reduction in the pericardial
      PAA of group Z (non-CPB) animals did not reach significance. For both group X and
      group Z the progress of mesothelial damage, compared with that at zero time,
      showed a significant increase. In addition, their pericardial inflammatory
      features became more apparent in the later samples but more significantly in
      group Z. This study demonstrated no significant short-term differences in
      adhesion formation or postoperative coronary anatomy visibility between any of
      the groups. At reoperation the patch material contained pronounced macrophage
      activity but no regenerative mesothelium. There were no infective episodes in any
      of the animals studied. Furthermore, this study suggests that CPB in comparison
      to non-CPB has a significant affect on pericardial PAA.

PMID- 9618809
TI  - Mediastinitis without antecedent surgery.
AB  - The study evaluates the results of aggressive surgical treatment for
      mediastinitis without antecedent surgery, after retrospectively reviewing all
      patients with mediastinitis, excluding patients with prior cardiac, esophageal or
      mediastinal operations, treated between June 1, 1992 and August 1, 1996. 8
      patients were treated. 7 were male, mean age was 58 years. The etiology was
      Boerhaave's syndrome in 4, iatrogenic injury in 2 and descending necrotizing
      mediastinitis in 2 patients. The mean number of operations was 2.5. The initial
      operation was through thoracotomy in 5 patients and sternotomy in 2 patients. 4
      patients underwent neck drainage, 1 as primary treatment and 3 combined with
      transthoracic drainage. 1 patient received laparotomy. Mean hospitalization was
      52 days (excluding 1 death). Complications included mechanical ventilation
      greater than 48 hours in 7 patients, 2 or more operations in 5 patients,
      multisystem organ failure in 5 patients and other complications in 6 patients.
      Death occurred in one patients. Mediastinitis without antecedent surgery is
      associated with significant morbidity, however, with aggressive surgical drainage
      87% of patients survived.

PMID- 9618810
TI  - Percutaneous dilatational tracheostomy done early after cardiac surgery--outcome
      and incidence of mediastinitis.
AB  - During November 95 to April 97, 45 percutaneous dilatational tracheostomies were
      performed in a nonselected patient series of 2788 open cardiac surgery cases.
      Tracheostomy was performed as early as the 2nd postoperative day (median: 6th
      day), when extubation was not foreseen within the next few days. Duration of
      intubation was 13 days (mean). We observed 6 complications in 5 patients (13.3%),
      namely bleeding, misplacement of the tube, subcutaneous emphysema, and
      superficial infection of the tracheostoma. Mediastinitis and wound infection of
      the sternal wound did not occur in any single case. There was no death due to
      tracheostomy. Clinically evident tracheal stenosis and inadequate granulation of
      the stoma were not observed after extubation. In our opinion, percutaneous
      dilatational tracheostomy is justifiable, shows good results, and entails minimal
      risk if done early after cardiac surgery, and it is also superior to standard
      surgical tracheostomy. Increased incidence of mediastinitis was not seen.

PMID- 9618811
TI  - Effect of lung allograft ischaemia duration on postreperfusion graft function and
      postoperative course.
AB  - Lung transplantation is limited by the effects of ischaemia. Previous clinical
      studies related graft ischaemia duration to post-operative pulmonary function in
      the ICU, morbidity, and overall survival. This report describes the
      intraoperative pulmonary allograft function immediately after reperfusion. 23
      lung transplantations (15 bilateral, 8 single) were analysed. Donor selection and
      organ procurement were identical. After pulmonary vasodilation with prostacyclin,
      allografts were flush-perfused with cold modified Euro-Collins solution. Mean
      duration of lung ischaemia was 255.1 +/- 35.1 min (190-314 min). Ischaemia times
      did not differ with respect to the recipient's disease or the use of
      extracorporeal circulation. After reperfusion, oxygenation indices deteriorated
      in 73.9% of patients compared with the native lungs (313.4 +/- 163.5 vs 427.2 +/-
      96.1, p = 0.006). Linear regression analysis and subgroup analysis both revealed
      a significant influence of the duration of allograft ischaemia on early
      transplant function. Ischaemia of more than 4 hours resulted in an acceptable but
      significantly lower PaO2 (254.9 +/- 143.3 mmHg vs 463.0 +/- 149.2 mmHg, p =
      0.011). However, mean time until extubation and time spent in the ICU were not
      affected. It is concluded that flush-perfusion of the lung with modified Euro
      Collins solution provides reliable preservation of lung function up to four
      hours. Longer ischaemia, up to six hours, is followed by an acceptable but
      progressively reduced early transplant function.

PMID- 9618812
TI  - The "T-shaped" thoracotomy for pericardiectomy after midline crossed IMA
      grafting.
AB  - In the presence of an internal mammary artery graft crossing the mid-sternal
      line, a median sternotomy may jeopardize the graft and consequently bring a
      hemodynamic compromise. We describe a case of successful radical pericardiectomy
      for postoperative constrictive pericarditis using a "T-shaped" thoracotomy in a
      68-year-old male patient who had a right IMA graft to the left anterior
      descending coronary artery.

PMID- 9618813
TI  - Repeat coronary artery bypass in a patient with liver cirrhosis.
AB  - The case of a 69-year-old man with liver cirrhosis, thrombocytopenia, unstable
      angina, and a history of previous coronary artery bypass grafting (CABG) is
      presented. The patient under-went successful repeat CABG through lateral
      thoracotomy on the beating heart without extracorporeal circulatory support.

PMID- 9618814
TI  - Intrapericardial pheochromocytoma.
AB  - Pheochromocytoma are catecholamine-secreting tumors occurring in less than 1% of
      the hypertensive population. Even though more sensitive methods have facilitated
      the diagnosis of intrathoracic paragangliomas they still remain extremely rare.
      This study reports a patient with a cardiac pheochromocytoma in whom the tumor
      was located on the outside of the roof of the left atrium and involved the left
      main coronary artery. Due to this anatomy the resection of the tumor required a
      cardio-pulmonary bypass and transsection of the pulmonary artery. The
      postoperative course was uneventful and the patient could be discharged without
      significant hypertension.

PMID- 9618815
TI  - An uncommon complication of Behcet's disease: intracardiac thrombosis needing
      surgical treatment.
AB  - Behcet's syndrome is a multisystem disorder presenting with recurrent oral and
      genital ulcerations as well as uveitis often leading to blindness. Although
      vascular lesions are a common complication of this disease, cardiac involvement
      is extremely rare. In this unusual case a young man had symptoms primarily
      related to recurrent right-atrial and right-ventricular thrombi unresponsive to
      medical treatment. The intracardiac lesion was successfully treated by surgical
      excision with the use of cardiopulmonary bypass. Surgical treatment should be
      considered in Behcet's disease complicated by cardiac thrombi, when a thrombus
      recurs despite medical treatment.

PMID- 9618816
TI  - Resection for CMV ileitis in a patient supported by a left-ventricular assist
      device.
AB  - We describe a patient requiring a HeartMate 1000 IP left-ventricular assist
      device (LVAD) due to cardiogenic shock. After prolonged gastrointestinal bleeding
      without identifying the source of bleeding technetium scintigraphy pointed to the
      right lower abdomen. The patient underwent a laparotomy and inflamed ileum was
      resected. Pathologic examination revealed cytomegalovirus ileitis. This was
      treated with ganciclovir and acyclovir. The patient is now (14 months later)
      awaiting heart transplantation since she could not be weaned from LVAD. The
      diagnostic and management problems are discussed as well as the relevance for
      future transplantation.

PMID- 9618817
TI  - De-epithelialization for esophageal cyst by video-assisted thoracoscopic surgery
      monitored by esophagoscopy.
AB  - In a 26-year-old male a congenital esophageal cyst was de-epithelialized using
      electro-cauterization via video-assisted thoracoscopic surgery (VATS) together
      with esophagoscopy. As the cyst adhered firmly to the esophageal muscle layer and
      mucosa, partial excision of the cyst and burning up of the cystic mucosa by
      electro-cauterization was performed to prevent esophageal mucosal perforation and
      postoperative esophageal dysmotility. Intraoperative video esophagoscopic
      monitoring enabled esophageal mucosal perforation to be avoided. Postoperative
      barium esophagography revealed good esophageal motility, and the patient showed
      no symptoms of esophageal dysmotility. We conclude that de-epithelialization for
      congenital esophageal cysts using VATS together with esophagoscopy is a minimally
      damaging and reasonable curative procedure without postoperative complications.

PMID- 9618818
TI  - Improved myocardial protection using continuous coronary perfusion with
      normothermic blood and beta-blockade with esmolol. A word of caution.

PMID- 9618819
TI  - [Pelvic osteotomy: a follow-up study of 36 patients].

PMID- 9618820
TI  - [Control of the identity of blood samples for the surveillance of research on
      swine vesicular disease and Aujeszky's disease].
AB  - A surveillance programme for swine vesicular disease (SVD) and Aujeszky disease
      was set up in 1993 in the Netherlands. Blood samples are taken from pigs by local
      veterinarians to enable testing for the presence of antibodies against these
      viruses. A programme to guarantee the identity of pigs tested for these diseases
      has been in operation since late 1995. In this programme, pigs are identified on
      the basis of the DNA profiles of blood and hair samples. The hair samples are
      collected by the department of Animal Health Control. Analysis proves whether
      blood and hair samples are from the same animal. A total of 655 animals have been
      tested from 94 farms. In 38.6% of these farms differences were found between
      blood and hair samples.

PMID- 9618821
TI  - [The risk of non-preventive culling].

PMID- 9618822
TI  - [Preventive culling: one compensation for lack of training].

PMID- 9618823
TI  - [Figurative use of antibiotics in hormone preparations].

PMID- 9618824
TI  - [Swine plague; welfare].

PMID- 9618825
TI  - [The role of the veterinarian at the farm of the future].

PMID- 9618826
TI  - [DAP Eelde-Hoornsemeer clear for the future].

PMID- 9618827
TI  - Augmentation rhinoplasty by subcutaneous midline forehead flap simultaneous with
      implant removal.
AB  - Implant exposure after augmentation rhinoplasty with alloplastic materials is
      usually associated with some degree of infection, and it is commonplace to remove
      the implant and wait for several months before re-augmentation. However, some
      patients cannot accept the resultant deformity after implant removal. We
      introduced the midline forehead flap for augmentation simultaneous to the removal
      and obtained favorable results, even when considering the donor site scar on the
      forehead. We report the surgical technique and two patients treated with this
      procedure. The advantages and disadvantages of this procedure are also discussed.

PMID- 9618828
TI  - Cerebral hemodynamics and histological changes following acute cerebral venous
      occlusion in cats.
AB  - Using an acute cerebral venous occlusion model prepared by injecting
      cyanoacrylate into the cerebral venous system, superior sagittal sinus pressure
      (SSSP) and regional cerebral blood flow (r-CBF) were measured. In the same model,
      changes in cerebral metabolism at the site of r-CBF measurement were observed
      using magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS).
      Cases were classified according to occlusion site: group SSS [occlusion of the
      superior sagittal sinus (SSS) only], group LS[occlusion of SSS plus lateral sinus
      (LS)] and group CV[SSS and LS plus cortical veins (CV)]. In groups SSS and LS,
      SSSP changed very little up to 6 hours after occlusion. In group LS, r-CBF
      decreased slightly, but the change was not significant. In contrast, an increase
      in SSSP and decrease in r-CBF were observed in group CV. Phosphorus MRS also
      demonstrated a decrease in phosphocreatinine (PCr) and adenosine triphosphate
      (ATP) and increase in inorganic phosphorus (Pi) following occlusion.
      Histopathological examination of group CV revealed dramatic changes, including
      the development of intracerebral hematoma and edema. Experimental application of
      the proposed model revealed that widespread occlusion of the sinuses can cause an
      increase in intravenous pressure with a concomitant decrease in r-CBF, resulting
      in metabolic complications such as a decrease in PCr and ATP and an increase in
      Pi.

PMID- 9618829
TI  - The immunodeficiency after allogeneic bone marrow transplantation in man: role of
      cytokines.
AB  - The effect of various cytokines including rIL-1, rIL-2, rIL-3, rIL-4, rIL-6, and
      growth factors including rNGF, rILGF and rEPGF on the post transplant
      immunodeficiency after allogeneic bone marrow transplantation was explored in 8
      patients. The results show that neither cytokine alone was able to increase the
      proliferative capability in post transplant lymphocytes, however, when added in
      conjunction a significant increase in PHA driven proliferation was noted. Any
      significant lack of growth factors is probably not the only cause of
      immunodeficiency post transplant, since addition of any of these compounds did
      not have any influence on the lymphocyte proliferation, and so the data presented
      here suggest that therapeutic application of any of the investigated cytokines or
      growth factors to such patients is unlikely to be successful in overcoming the
      defects of T cell function post grafting.

PMID- 9618830
TI  - Comparison of in vitro activity of azithromycin and ampicillin against 31
      isolates of Streptococcus milleri.
AB  - Antibacterial action of azithromycin against 31 strains of dental infection
      derived Streptococcus milleri and tissue transfer of the agent were compared with
      ampicillin, the drug of first choice for dental infections. Concentrations
      required to inhibit 50% of isolates(MIC50) and Concentrations required to kill
      50% of isolates(MBC50) were 0.10 and 0.2 microgram/ml, respectively, for
      azithromycin. The antibacterial action of azithromycin was 4 times more potent in
      than ampicillin. The MBC90 for azithromycin was 0.39 microgram/ml, for amplicill
      3.13 micrograms/ml. Bactericidally, azithromycin was 8 times more active than
      ampicillin. The peak value of concentrations (Cmax) of azithromycin was 0.45
      microgram/ml, about 1/10 that of ampicillin. The half-life of azithromycin was 10
      hours, about 5 times longer than that of ampicillin. The contact time of MIC90
      concentrations for azithromycin was 12 hours, distinctly longer than the 8 hours
      calculated for ampicillin. Azithromycin showed excellent tissue transfer
      concentrations: the gingival transfer concentration following oral administration
      of 500 mg/day ranged from 0.7-23.5 micrograms/ml.

PMID- 9618831
TI  - Effect of procaine and oxethazaine on muscarinic receptors of parietal cells.
AB  - Several reports have shown that local anesthetics have a high affinity for
      muscarinic receptors and competitively inhibit the effects induced by cholinergic
      agents in various tissues, but there have been no reports on the muscarinic
      receptors of parietal cells. The effects of five doses of procaine (10(-8)M
      approximately 10(-4)M) and seven doses of oxethazaine (10(-8)M approximately 10(
      5)M) on 14C-aminopyrine accumulation in isolated parietal cells of guinea pigs
      induced by 10(-4)M carbachol were studied. Procaine showed a potentiating effect
      with peak potentiation at a dose of 10(-5)M, while oxethazaine showed an
      inhibitory effect in a dose-dependent manner at doses higher than 3 x 10(-8)M and
      suppression below the control levels at doses higher than 3.5 x 10(-7)M. Procaine
      alone increased 14C-aminopyrine accumulation with peak response at a dose of 10(
      5)M, while oxethazaine alone showed an inhibitory effect in a dose-dependent
      manner at doses higher than 3 x 10(-8)M. Oxethazaine shifted the carbachol dose
      response curves to the right with suppression of maximal response. In conclusion,
      in parietal cells, procaine appears to display roughly similar action to
      carbachol through muscarinic receptors, while oxethazaine displays inhibitory
      action mainly by mechanisms other than inhibition at the muscarinic receptor
      site.

PMID- 9618832
TI  - Expression of glutathione-peroxidase (GSH-PO) in the rat ventral prostate--effect
      of castration and administration of testosterone.
AB  - Immunolocalization of glutathione-peroxidase (GSH-PO), apoptosis and bcl-2
      protein in the rat ventral prostate was investigated in the presence or absence
      of androgen. Male Sprague-Dawley rats were divided into four experimental groups.
      Group 1 consisted of intact controls. In group 2, rats were sacrificed two days
      after castration. In groups 3 and 4, rats were administered subcutaneously 1
      mg/animal of testosterone-propionate daily for three or seven days at two days
      after castration. The intensity of GSH-PO staining in the glandular epithelial
      cells of the ventral prostate was remarkably decreased after castration (Group
      2), and it clearly recovered when testosterone was administered (Groups 3 and 4)
      to the castrated rats. The prostatic GSH-PO mRNA levels were diminished in the
      castrated rat ventral prostate but greatly increased by testosterone (Groups 3
      and 4). Furthermore, castration (Group 2) induced apoptosis in the prostatic
      glandular epithelial calls and the apoptosis was reduced by testosterone
      administration (Groups 3 and 4) to the castrated rats. In groups 3 and 4,
      expression of bcl-2 protein was clearly detected in the glandular epithelial
      cells of the ventral prostate. These findings strongly suggested that expression
      of GSH-PO and bcl-2 protein in the glandular epithelial cells of the rat ventral
      prostate is testosterone-dependent.

PMID- 9618833
TI  - Two different hard palate closure techniques in two-stage palatoplasty: effects
      on velopharyngeal closure and articulation.
AB  - Two different hard palate closure techniques, in two-stage palatoplasty, was
      evaluated in 12 patients. The lip and soft palate were closed at 3 to 7 months of
      age. The patients were then divided into two groups of six and the hard palate
      closed at 17 to 23 months of age, either by a vomer flap (VF) with a skin graft
      (Osada's two-stage palatoplasty) in the VF group, or by the push-back (PB)
      procedure of the mucoperiosteal flap in the PB group. Velopharyngeal closure
      (VPC) during a gag reflex before and after hard palate closure, and the
      articulation of these patients after closure, were evaluated and compared between
      the two groups. Regarding VPC before hard palate closure, three "Poor" and three
      "Borderline" outcomes were noted in each group. We conclude that, by introducing
      the pharyngeal flap, the patients in the VF group obtained good articulation,
      actually comparable to that in the PB group.

PMID- 9618834
TI  - Cardiac extension of intravenous leiomyomatosis with successful resection.
AB  - A case of intravenous leiomyomatosis spreading to the right ventricle is
      described. A 28-year-old woman had been previously diagnosed as having a smooth
      muscle tumor of borderline malignancy after hysterectomy for a large uterine
      tumor, because of its unusual invasive character. Based on the above diagnosis,
      the patient had been managed clinically as having a uterine sarcoma. One year
      after her hysterectomy, a local recurrence in the pelvic cavity was detected. Two
      years later, the tumor appeared as a cardiac tumor causing syncope. The tumor was
      totally resected in two surgical stages, and the correct diagnosis of an
      intravenous leiomyomatosis was made. The diagnostic and operative considerations
      are reviewed and the preferred surgical procedure is discussed.

PMID- 9618835
TI  - A statistical study of fistula auris congenita in Japan.
AB  - A statistical study of the occurrence, in Japan, of fistula auris congenita was
      conducted in 15,114 subjects (8,018 elementary school and 7,096 junior high
      school students) in Kanagawa, Shizuoka, and Wakayama Prefectures. The incidence
      of fistula auris congenita was 2.6% (396 of 15,114 students). Many cases were
      unilateral and exhibited a single manifestation. The fistula sites were mainly in
      the preauricular region. Only 2.3% of the 396 fistula cases had a history of
      radical operation.

PMID- 9618836
TI  - Visual-vestibular interaction--an evoked potential study in normal human
      subjects.
AB  - Positron emission tomography (PET) was used to demonstrate temporary down
      regulation of visual cortex activities associated with eye movements. The aim of
      the present study was to test this paradigm with visual evoked potentials (VEPs)
      in the visual cortex of 7 healthy human subjects during caloric nystagmus.
      Caloric stimulation was performed by irrigating the right or left external ear
      canals with 100 ml of warm water at 44 degrees C for 50 s with a head position of
      60 degrees tilted backward in order to stimulate the horizontal semicircular
      canal. The subjects kept their eyes closed during and after caloric stimulation.
      For recording the VEPs, the flashlight was used for activating the visual cortex
      with the subject's eyes closed. In the 7 subjects, no significant difference was
      detected between the VEPs induced with and without caloric stimulation.

PMID- 9618837
TI  - [Staff certification for mobile blood collection units].
AB  - Training and official acknowledgment of the competence of each staff member are
      essential to the quality and safety of collected blood products prepared and
      delivered by a blood transfusion center. A procedure was created to indicate in
      detail the methods employed to implement such accreditation. Based on individual
      training according to activity, it defines for each type of activity (secretary,
      physician, collector, driver) the required theoretical and practical knowledge of
      his/her position. Accreditation, consisting of assessment of the degree of
      competence attained in these areas of responsibility, was applied to the members
      of mobile blood collection teams in 1995. No major deficiency was detected, and
      this certification was well accepted by the staff. In order to complete this
      initial accreditation, blood collection abnormalities (inadequate blood volumes,
      clots or defective welding of tubing) were assessed for each collector
      individually. Comparison of these abnormalities in qualified nurses and
      laboratory technicians with a blood collection diploma showed no differences. On
      the other hand, significantly higher numbers of abnormalities were found in
      intermittent as compared to regular collectors and in senior as compared to new
      collectors. The applied corrective measures led to obviation of differences and
      improvement in performance. In 1996, in the first individual evaluation of
      medical selection carried out by each physician, discrepancies of one to 20
      donors (0.7-14.2%) were observed from one doctor to another in the frequency of
      elimination of candidates for blood donation after the medical interview. Regular
      meetings with physicians resulted in reducing these discrepancies to one to 3.1
      donors (4.6-14.1%) in 1997. In conclusion, the association of an initial
      accreditation procedure with an individual follow-up of work quality allowed
      satisfactory assessment of the training and competence of staff members. This
      kind of method could be extended to those working in other fields of transfusion
      medicine.

PMID- 9618838
TI  - [Quality control of homologous blood collection activities: 5 years' experience].
AB  - Quality control (QC) of blood collection activities for transfusion is a
      regulatory requirement. The authors report on their experience in this field over
      the past 5 years. In their institution, this QC is based on both the recording
      and analyzing of predefined data, as well as the search for an active
      collaboration from each person involved in these activities. QC of medical
      selection relies on the assessment of several associated criteria: effectiveness
      of the information given to blood donors for recruitment, preparation of the
      medical interview and encouragement to perform regular donations; frequency of
      donors deferred after the medical interview; frequency of biological
      abnormalities detected at donation; results of the inquiries into the
      corresponding medical interviews following adverse transfusion reactions. The
      quantitative and qualitative evaluation of blood collection permits assessment of
      the quality of the blood collection program, collection procedures and directly
      derived blood products. Quality assessment of facilities and equipment is also
      included in this QC. Results have been improving in recent years, especially
      regarding medical selection. In particular, an increase in the mean donation rate
      of donors, a decrease in biological abnormalities detected at donation and an
      absence of adverse transfusion reactions attributed after inquiry to an
      inadequate medical interview have been noticed. A decrease in both shortage and
      outdating of labile blood products likewise indicates an improvement of blood
      collection planning. However, this QC reveals deficiencies in the information
      given to donors and a lack of analysis of the data specific to first time donors.
      In order to further improve the efficiency of QC, these results now require
      comparison with similar data collected on a nation-wide scale.

PMID- 9618839
TI  - [Detection of the nucleic acids of hepatitis B and C viruses and human
      immunodeficiency virus for the biological screening of blood donations. Viral
      Hepatitis and Retrovirus Working Groups and Subgroup for Molecular Biology
      Applied to Transfusion Virology of the French Blood Transfusion Society].
AB  - Direct viral DNA or RNA detection by genomic amplification methods should
      contribute to the improvement of blood supply safety by reducing the pre
      seroconversion window period. However, nucleic acid testing may not eliminate
      virus transmission from window period donations. Moreover, the virus subtype
      diversity has to be taken into account for the choice of nucleic amplification
      assays. Technology for nucleic acid testing has not been developed to be
      implemented in blood screening laboratories. The limitations of these procedures
      are mainly linked to the difficulties related to the automation of sample
      processing and to the possibilities of cross contamination of samples due to the
      high sensitivity of amplification methods. The extreme complexity of nucleic acid
      testing for single donation screening (development of an on-site automated high
      throughput instrumentation, training, specialized facilities for sample
      processing, amplification and detection...) and its high cost mean that
      strategies using amplification testing of pooled samples should be developed.

PMID- 9618840
TI  - [Update on hepatitis C virus: its variability and the implications].
AB  - Hepatitis C virus (HCV) is the main etiologic factor of post-transfusional and
      sporadic hepatitis, called non-A non-B in the past. These infections are
      characterized by a very high number of chronic carriers always with a persistent
      viral increase, but often at a slow pace. The seriousness of liver disease
      differs from one individual to another, varying from an asymptomatic form with
      minor or no liver injuries, to cirrhosis and hepatocellular carcinoma.
      Physiopathological mechanisms involved in liver injuries are still poorly
      understood. The direct role of immune response and of possible genetic factors is
      still under study. This review aims at summing up the discovery of HCV, its
      structure, and its variability in the various genome regions in the same
      individual and from one individual to another. The different methods and
      techniques to analyze this variability are also reviewed, as well as the various
      suggested ways of classifying the different types. The geographical distribution
      and both clinical and biological consequences of this variability are also
      discussed.

PMID- 9618841
TI  - [Hemoglobin beta S haplotype in the Kebili region (southern Tunisia)].
AB  - Sickle cell anemia is a monogenic hereditary disease characterized by a mutation
      in the beta globin gene. Five major haplotypes associated with the beta S
      mutation have been defined: Benin, Bantu, Senegalian, Camerounian, and Arabo
      Indian. Previous studies in northern Tunisia showed that sickle cell anemia was
      of Benin origin in this region. Patients from the south of Tunisia, mainly from
      the Kebili region, were not previously concerned. In this study, we have
      determined the beta S haplotype and evaluated phenotypical expression of the
      disease in 14 patients from this latter region. The use of four restriction
      endonucleases having polymorphic sites in the beta globin gene showed that all
      patients had the Benin haplotype, confirming the Benin origin of sickle cell
      anemia in Tunisia. This haplotype is associated with an heterogeneous expression
      of fetal hemoglobin (HbF) with extremes varying from 2.4 to 16.3% and a mean
      expression rate of 8.16%, which is in accordance with literature data. In spite
      of the haplotype homogeneity in our patients, clinical heterogeneity was noted. A
      unique case of alpha-thalassemia could not explain this heterogeneity. In
      contrast, we found a certain correlation between fetal hemoglobin expression and
      clinical severity.

PMID- 9618842
TI  - Perinatal aspects of preterm intrauterine growth restriction.

PMID- 9618843
TI  - Prenatal scrotal ultrasound: providing new clues in cryptorchidism.

PMID- 9618844
TI  - Sonographic diagnosis of conjoined twinning.

PMID- 9618845
TI  - Development of fetal male gender: prenatal sonographic measurement of the scrotum
      and evaluation of testicular descent.
AB  - The study was conducted to construct a centile chart of fetal scrotal size and to
      determine gestational age at testicular descent. A prospective, cross-sectional
      study was performed on 210 fetuses of normal, singleton pregnancies between 14
      and 37 weeks' gestation. Scrotal circumference was measured by transvaginal
      ultrasonography and abdominal ultrasound between 14 and 17 weeks' and 18 and 35
      weeks' gestation, respectively. The regression equation for scrotal circumference
      (SC) modelled as a function of gestational age (GA) was: SC (mm) = exp (1.05 +
      0.09 GA (weeks)) The correlation r = 0.96 was found to be highly statistically
      significant (p < 0.0001). The prediction of scrotal circumference per week and
      the 95% confidence interval (CI) were defined. Testicular descent was not
      observed prior to 2.5 weeks' gestation, with 30% of the fetuses having one or
      both testes descended at 25 weeks (p < 0.001) and 97% after 32 weeks. The
      presented normative data may be helpful in the prenatal diagnosis of suspected
      congenital syndromes that include, among their manifestations, scrotal
      abnormalities and early detection of cryptorchidism.

PMID- 9618846
TI  - Comparison of prenatal ultrasound and postmortem findings in fetuses and infants
      with central nervous system anomalies.
AB  - Detection of fetal developmental abnormalities by ultrasound examination of
      pregnant women has become a specialized field of medicine. Quality control of
      this field requires detailed examination of aborted fetuses. In 408 fetuses and
      infants with developmental anomalies, the prenatal ultrasound findings were
      compared with the post-mortem findings. This study focused on 140 central nervous
      system (CNS) anomalies. Criteria for inclusion were an ultrasound examination at
      the National Center for Fetal Medicine (NCFM) and an autopsy performed during the
      period 1985-94. Results of the ultrasound and autopsy examinations were
      systematized into six different categories. Hydrocephaly and anencephaly were the
      most frequent abnormalities, together accounting for 50% of the CNS anomalies. In
      20 cases (14%), the CNS anomalies were associated with other important anomalies
      or chromosomal aberrations. In 125 of the cases (89%), there was complete
      concordance between the ultrasound and autopsy diagnoses. Of the 15 CNS cases
      with discrepancies, seven had nearly complete concordance; if we include these,
      the correlation was 94%. In conclusion, this study confirms that developmental
      anomalies in the central nervous system are frequent and that ultrasound
      diagnoses are in good concordance with the autopsy diagnoses.

PMID- 9618847
TI  - Sonographic diagnosis of fetal coarctation of the aorta at 14-16 weeks of
      gestation.
AB  - The prenatal sonographic diagnosis of coarctation of the aorta is difficult. The
      objective of this study was to present a simple and reliable marker of this
      anomaly in early pregnancy. In fetuses with coarctation of aorta who were scanned
      at 14-16 weeks' gestation, a significant discrepancy was observed between a large
      ductus arteriosus and a smaller aorta at their point of connection. This
      difference between the sizes of the vessels probably reflects the reduced blood
      flow through the aorta and the compensatory increase in blood flow through the
      right outflow tract in cases of coarctation of the aorta.

PMID- 9618848
TI  - The optimal gestational age to examine fetal anatomy and measure nuchal
      translucency in the first trimester.
AB  - The objective of this study was to determine the optimal gestational age for
      examining fetal anatomy and nuchal translucency in the first trimester. In a
      prospective cross-sectional study, 1288 women from an unselected population
      underwent a detailed assessment of fetal anatomy at 10-14 weeks of gestation
      (confirmed by crown-rump length) with the use of transabdominal sonography and
      transvaginal sonography, when necessary. Visualization of fetal anatomy improved
      with increasing gestational age: 6, 75, 96, and 98% of cases could be visualized
      at 10, 11, 12 and 13 weeks of gestation, respectively, and was similarly high
      (98%) at 14 weeks. The ability to measure nuchal translucency was similar from
      weeks 10 to 13 (100, 98, 98 and 98% success rate), but fell to 90% at 14 weeks.
      The need for transvaginal sonography steadily decreased with increasing
      gestational age, being 100, 42, 21, 15 and 11% at 10, 11, 12, 13 and 14 weeks,
      respectively. From these data it appears that the optimal gestational age to
      examine fetal anatomy and measure nuchal translucency in the first trimester is
      13 weeks.

PMID- 9618849
TI  - Assessment of first-trimester nuchal translucency by daily reference intervals.
AB  - Increased fetal nuchal translucency measured in the first trimester is associated
      with an elevated frequency of chromosomal abnormalities, yet no reference
      intervals for transvaginal sonographic measurements of fetal nuchal translucency
      in that period of development have been established. The aim of the present cross
      sectional study was to construct appropriate gestational age-specific reference
      intervals for nuchal translucency. Transvaginal ultrasound was used in 180 normal
      pregnant women between 9 and 14 weeks of gestation. Reference intervals were
      constructed by the parametric method. These reference intervals were then
      compared to the traditional threshold value of 3 mm, when applied to 287 women
      scheduled for amniocentesis or chorionic villus sampling (CVS). Both methods had
      the same sensitivity, 85.7%, and negative predictive value, 99.6%, in predicting
      fetal chromosomal abnormalities. However, the specificity of the gestational age
      related reference intervals tended to be higher than that of the 3-mm threshold:
      94.6% vs. 87.9%. The positive predictive value of the former method was higher
      than that of the 3-mm threshold: 28.6% vs. 15%. The increased specificity and
      positive predictive value of these reference intervals are of particular
      importance when applied to women under the age of 35 years. In those women, the
      finding of an abnormally thick nuchal translucency can lead to the performance of
      amniocentesis or CVS. Therefore, using these reference intervals instead of the
      traditional 3-mm threshold may save a significant number of unnecessary invasive
      procedures.

PMID- 9618850
TI  - Image magnification does not contribute to the repeatability of caliper placement
      in measuring nuchal translucency thickness.
AB  - The objective of this study was to assess whether nuchal translucency image
      magnification contributes to the repeatability of caliper placement. Twenty-seven
      women undergoing first-trimester ultrasound screening at 11-14 weeks were
      examined by two qualified examiners. Fetal nuchal translucency thickness was
      measured twice by each examiner on a regular-sized image and subsequently on the
      same still image magnified. Intraobserver repeatability coefficients of the
      regular-sized images were 0.28 mm and 0.34 mm for examiners A and B,
      respectively. Identical intraobserver repeatability coefficients of 0.28 mm were
      attained for both examiners on the magnified images. Interobserver repeatability
      of regular-sized image measurements showed a significant difference (p < 0.01)
      but the mean difference (+/- standard deviation) of 0.10 (0.18) mm was
      negligible. Similarly, interobserver repeatability of the magnified-image
      measurements yielded a significant difference (p < 0.02), but again with a small
      mean difference of 0.13 (0.26) mm. There were also significant differences when
      regular-sized images and magnified images were compared for both examiners: 0.08
      (0.16) mm for examiner A (p < 0.02) and 0.10 (0.17) mm for examiner B (p < 0.01).
      Our results demonstrate that nuchal translucency image magnification does not
      contribute to the reproducibility of the measurement. Despite significantly
      smaller mean values obtained from the magnified images, compared to the regular
      sized measurements, those differences do not justify modification of the criteria
      for caliper placement on magnified images. Blind repeated measurements on a
      regular-sized and/or magnified image are recommended as a tool for self
      assessment, quality control and training.

PMID- 9618851
TI  - The effect of nuchal cord on nuchal translucency measurement at 10-14 weeks.
AB  - The aim of this study was to determine the incidence of nuchal cord and its
      possible effect on nuchal translucency thickness at 10-14 weeks' gestation. Out
      of 316 consecutive pregnancies in which nuchal translucency thickness was
      measured transabdominally, 26 (8.23%) fetuses were shown to have the umbilical
      cord around the neck. The umbilical cord can be measured together with the nuchal
      translucency thickness when it passes around the fetal neck and this adds a mean
      of 0.8 mm to the actual translucency measurement. After the thickness of the cord
      was subtracted, the measurements of nuchal translucency thickness did not differ
      from those in the overall population studied. Of the 22 fetuses available for
      follow-up, a nuchal cord was found in only one at 20 weeks and in none at
      delivery. Our findings indicate that the presence of a nuchal cord may bias the
      results of fetal nuchal translucency measurement and that the use of color
      Doppler might decrease the false-positive rate in screening for fetal aneuploidy
      by nuchal translucency measurement at 10-14 weeks' gestation.

PMID- 9618852
TI  - Variation of embryonic/fetal heart rate at 6-13 weeks' gestation.
AB  - The aim of this study was to investigate changes in heart rate, namely the
      intraindividual variation, in normal embryos/fetuses between 6 and 13 weeks'
      gestation. A prospective study was performed of 41 singleton pregnancies
      undergoing routine ultrasound examination during the first trimester of
      pregnancy. For each case, the embryonic/fetal heart rate was measured on three
      consecutive occasions with a mean interval of 4 min. The difference in heart rate
      values between the serial measurements varied from 0 to 18 beats/min and was
      significantly associated with gestational age (Spearman r = 0.26, p < 0.01). In
      the group of 15 fetuses (examined before 10 weeks' gestation), the difference
      between measurements (median = 0 beats/min, range 0-8 beats/min) was
      significantly lower (z = 2.48, p < 0.05) than in fetuses assessed after 10 weeks
      of gestation (median = 3, range 0-18 beats/min). Reliable and reproducible
      information concerning embryonic/fetal heart rate may be obtained from a single
      measurement, especially when pregnancies are examined before 10 weeks of
      gestation.

PMID- 9618853
TI  - Diagnosis of adnexal malignancies by using color Doppler energy imaging as a
      secondary test in persistent masses.
AB  - The purpose of this prospective study was to compare the accuracy of B-mode
      transvaginal ultrasonography alone and in combination with color Doppler energy
      (or power Doppler) imaging in differentiating benign from malignant adnexal
      masses. A total of 192 consecutive persistent adnexal masses (159 benign, 33
      malignant) were studied before surgery by B-mode transvaginal ultrasonography
      with and without color Doppler energy. In addition, CA-125 plasma levels were
      determined and spectral Doppler analysis was performed. By color Doppler energy
      imaging, a mass was considered malignant when arterial flow was visualized in an
      echogenic portion of a mass defined as malignant by B-mode. Intratumoral arterial
      blood flow could be readily detected by color Doppler energy imaging in all
      malignant tumors and in 94% of the benign tumors. The combined use of
      transvaginal B-mode ultrasonography and color Doppler energy imaging has greater
      accuracy in the diagnosis of ovarian malignancies than transvaginal
      ultrasonography alone (value of kappa: 0.81 and 0.63, respectively), reducing the
      number of false-positive results. The use of spectral Doppler analysis was of
      limited diagnostic value, with a kappa value of 0.17 for the pulsatility index (<
      1) and of 0.41 for the resistance index (< 0.4). Also, the association with CA
      125 increased the number of false-negative results. In conclusion, the use of
      color Doppler energy imaging seems to be a useful secondary test when a mass is
      suspected to be malignant by B-mode ultrasonography.

PMID- 9618854
TI  - Uterine artery blood flow parameters in women with dysfunctional uterine bleeding
      and uterine fibroids: the effects of tranexamic acid.
AB  - The objective of this study was to investigate the effects of tranexamic acid on
      uterine vascular resistance in women with dysfunctional uterine bleeding and in
      women with menorrhagia associated with fibroids. A longitudinal, prospective
      study was carried out in premenopausal women referred to a gynecological
      outpatient department with a complaint of menorrhagia. We studied 24 women with
      dysfunctional uterine bleeding (mean age 38.8 years; normal ultrasound
      examination, hysteroscopy and endometrial biopsy) and 12 women (mean age 42.8
      years) with at least one fibroid greater than 2.0 cm on ultrasound examination.
      None were on any form of oral contraception or other medication which could
      influence uterine vascular resistance. All women had normal coagulation and
      thyroid function tests. Transvaginal scanning was performed using an Aloka SSD
      650 machine with a 5-MHz probe and pulsed Doppler. Pulsatility index (PI) and
      resistance index (RI) were measured from the left and right uterine arteries
      before and during the second month of treatment with tranexamic acid (1 g orally
      three times a day). Menstrual blood loss was assessed using a validated pictorial
      blood chart. In women with dysfunctional uterine bleeding, the mean PI and RI
      fell significantly with treatment (PI 2.20-1.94, p = 0.0001; RI 0.81-0.77, p =
      0.003). There was a reduction of approximately 30% in menstrual blood loss with
      treatment (210.0-137.6 ml, p = 0.0001). In women with uterine fibroids, there was
      no significant change in either the PI or the RI with treatment and there was no
      significant reduction in menstrual blood loss. We conclude that tranexamic acid
      significantly reduces uterine artery vascular resistance in women with
      dysfunctional uterine bleeding. This effect is unlikely to be a mechanism for the
      action of tranexamic acid in reducing menstrual blood loss but may have important
      implications for women taking this treatment in the long term.

PMID- 9618855
TI  - Prenatal diagnosis of testicular torsion.
AB  - A case of the prenatal diagnosis of testicular torsion at 39 weeks' gestation is
      presented. The affected testicle was observed as a small rounded area of
      hypoechogenicity with a peripheral echogenic ring without hydrocele. The
      appearance was suggestive of the chronic phase of testicular torsion. The
      neonatal genital exploration confirmed the diagnosis.

PMID- 9618856
TI  - Prenatal sonographic diagnosis of conjoined twins in the first trimester: two
      case reports.
AB  - Conjoined twins are a rare occurrence. We present two cases of conjoined twins
      diagnosed by ultrasound examination at 8 and 13 weeks' gestation, respectively.
      These cases demonstrated the possibility of making an accurate diagnosis of
      conjoined twins and delineating the extent of organ sharing in the first
      trimester.

PMID- 9618857
TI  - Three-dimensional transvaginal sonography of conjoined twins at 10 weeks: a case
      report.
AB  - Early and accurate prenatal diagnosis of conjoined twins is still a challenge,
      and is important when planning a favorable outcome for the mother and infants. We
      present a case diagnosed with transvaginal and three-dimensional ultrasound at 10
      weeks of gestation, and discuss the contribution of this relatively new scanning
      modality.

PMID- 9618858
TI  - Trisomy 22: a cause of isolated fetal growth restriction.
AB  - The management of severe isolated fetal growth restriction at term involves
      consideration of the risk of associated aneuploidy. A case is described in which
      intrauterine growth restriction was detected at 37 weeks' gestation in a
      structurally normal fetus. The diagnosis of trisomy 22 was made after fetal blood
      sampling. This diagnosis has not been previously reported in a structurally
      normal fetus. This case highlights the dilemma that arises in the management of
      the small, structurally normal fetus in the late third trimester. The reasons for
      survival to term of some trisomy 22 fetuses are as yet unclear and are discussed.

PMID- 9618859
TI  - Early transvaginal ultrasonographic diagnosis of Beemer-Langer dysplasia: a
      report of two cases.
AB  - The early second-trimester sonographic diagnosis of two infants with short rib
      (polydactyly) dysplasia type IV (Beemer-Langer dysplasia) is presented. In
      addition to short ribs, this syndrome is characterized by short limbs with or
      without polydactyly. There are often associated defects, particularly neural-tube
      anomalies. The occurrence of consanguinity and of four affected siblings in this
      family support autosomal recessive inheritance.

PMID- 9618860
TI  - Delayed fusion of amnion and chorion: a possible association with trisomy 21.

PMID- 9618861
TI  - Cystic type IV sacrococcygeal teratoma detected at 18-week prenatal ultrasound.

PMID- 9618862
TI  - Presentation of the Ian Donald Gold Medal to Lindsey Allan.

PMID- 9618863
TI  - Presentation of the Ian Donald Medal for Technical Development to Klaas Bom.

PMID- 9618865
TI  - Investigation of splenic functions in canine monocytic ehrlichiosis.
AB  - In order to determine the role of the spleen in the pathogenesis of canine
      monocytic ehrlichiosis (CME), the effect of splenectomy on the course of the
      acute phase of experimental was investigated. Intact and splenectomized dogs,
      sero-negative for Ehrlichia canis antibodies, were infected with the Israeli
      strain of E. canis. Serology, clinical signs and haematological parameters were
      recorded prior to infection, and over a period of 60 days post infection, and
      were compared between the intact and the splenectomized dogs. All dogs
      seroconverted for IFA E. canis antibodies by days 10 to 17 post infection. There
      did not appear to be any difference in the day of appearance or in the titer of
      anti-E. canis IgG antibodies, between the splenectomized and intact groups
      throughout the course of the study. During the acute stage, food consumption
      (percentage change) was significantly lower in the intact group compared to the
      splenectomized group (-66.3% and -25.3%, respectively, p < 0.0001). During this
      period, significant higher body temperatures were measured in the intact group
      (average of 39.76 degrees C vs. 38.96 degrees C, p < 0.0001). The haematocrit,
      red blood cell counts, haemoglobin concentrations and platelet counts were
      significantly lower (p < 0.05) in the intact group when compared to the
      splenectomized group during the whole course of the study. The clinical and the
      haematological findings in our study suggest that the disease process was milder
      in the splenectomized dogs compared to the intact dogs. The results of this study
      suggest that the spleen plays an important role in the pathogenesis of CME.
      Splenic inflammatory mediators and/or other splenic substances, are proposed to
      play a key role in the pathogenesis of the disease. Our results further
      substantiate the involvement of immune mechanisms in the pathogenesis of CME.

PMID- 9618864
TI  - Expression of major histocompatibility complex class II antigen in neoplastic
      cells of canine cutaneous histiocytoma.
AB  - Forty five cases of canine cutaneous histiocytoma (CCH) were examined by
      immunohistology for expression and distribution of major histocompatibility
      complex (MHC) class II antigen in neoplastic cells. In addition, expression of
      lysozyme and calprotectin (leucocyte protein L1) in neoplastic cells was
      investigated. Furthermore, B and T lymphocytes were demonstrated by antibodies
      against the CD3 antigen, IgG, and IgM. Neoplastic cells showed two staining
      patterns for MHC class II antigen: focal juxtanuclear cytoplasmic staining and/or
      rim-like staining along the cell periphery. In 24 cases, a predominant or
      exclusive focal juxtanuclear cytoplasmic MHC class II antigen reaction in
      neoplastic cells, and the presence of few diffusely distributed infiltrating CD3
      antigen-positive T lymphocytes were observed. Tumors with numerous neoplastic
      cells exhibiting staining for MHC class II antigen along the cell periphery (n =
      21) showed increased inflammatory alterations, represented by disseminated and
      nodular infiltrations of mainly CD3 antigen-positive T cells. B cells, plasma
      cells, exudate macrophages, and neutrophils were rarely seen disseminated between
      neoplastic cells whereas their number increased within focal inflammatory
      infiltrates. The focal cytoplasmic reaction for MHC class II antigen in
      neoplastic cells might represent newly synthesized MHC class II molecules stored
      in vesicles, whereas staining of the cell periphery might occur due to
      accumulation of MHC class II molecules along the plasma membrane. The increasing
      expression of MHC class II molecules on the cell surface might be the decisive
      factor for onset and progression of tumor regression. However, the exact
      mechanism of priming and activation of T cells by neoplastic cells and the nature
      of the presented antigen are not yet known.

PMID- 9618866
TI  - A simple method for the simultaneous separation of peripheral blood mononuclear
      and polymorphonuclear cells in the dog.
AB  - A simple method for the simultaneous separation and purification of peripheral
      blood mononuclear cells (PBMC) and polymorphonuclear neutrophil cells (PMNC) was
      developed for comparative and functional studies in the immune system of the dog.
      Purity and cell viability were > 95%, yields were similar to those obtained by
      other techniques but without red blood cell contamination. Differential blood
      cell count studies of the isolated cells in blood samples of beagle dogs and
      German shepherd dogs demonstrated that the 1.077/1.119 double density
      centrifugation is an effective method of acquiring both highly purified blood
      mononuclear cells and polymorphonuclear cells as separate entities from the same
      sample. The interface between plasma and 1.077 contained an average 97% blood
      mononuclear cells vs. 3% polymorphonuclear cells, and the interface between 1.077
      and 1.119 an average 96% polymorphonuclear cells vs. 4% blood mononuclear cells.
      These data indicate that Histopaque 1.077/1.119 double density gradient allows
      the purification and physical separation of lymphocytes and phagocytes from a
      blood sample in the dog, enabling the investigator to examine both cell types
      from the same sample simultaneously.

PMID- 9618867
TI  - The immune response of cattle, persistently infected with noncytopathic BVDV,
      after superinfection with antigenically semi-homologous cytopathic BVDV.
AB  - Cattle persistently infected (PI) with noncytopathic (ncp) bovine virus diarrhea
      virus (BVDV) are at risk for developing fatal mucosal disease (MD), which is
      considered to occur after superinfection with antigenically homologous cytopathic
      (cp) BVDV. In this study, we intranasally inoculated four PI-animals, that were
      PI with 2 ncp BVDV strains with 10(5) TCID50 antigenically closely related cp
      BVDV. Two PI-animals were inoculated with 10(5) TCID50 ncp BVDV and one PI
      animal, with virus free cell culture medium. Two out of four PI-animals that were
      inoculated with cp BVDV, developed MD and were euthanized at day 17 and at day 24
      after infection. Postmortem, both animals showed typical lesions of MD and cp
      BVDV was isolated. The other two PI-animals that were inoculated with cp BVDV did
      not develop MD and were euthanized at day 51. They showed ulcerations in the
      gastrointestinal tract, cp BVDV was isolated and neutralizing antibodies were
      detected. From the three PI-animals, that were inoculated with ncp BVDV or cell
      culture medium, cp BVDV was also isolated. Cross neutralization tests were
      performed and no antigenic differences could be detected between the cp strains
      isolated from the PI-animals. Lymphocyte subsets of these PI-animals were
      determined by flow cytometric analysis. Before superinfection, the percentages of
      gamma delta subsets were much higher in the PI-animals that did not develop MD
      than in nonviremic control animals and in the PI-animals that died of MD. From
      this study we conclude that the presence of antigenically closely related cp BVDV
      in PI-animals does not necessarily lead to the development of MD and that besides
      the antigenic relatedness between the persisting ncp BVDV and cp BVDV other
      factors, for instance the number of circulating gamma delta cells, might
      determine whether or not PI-animals develop MD.

PMID- 9618868
TI  - Effect of colostral ingestion on immunoglobulin-positive cells in calves.
AB  - The importance of colostrum for passive transfer of maternal immunoglobulin in
      calves is well established. Colostrum is thought to have additional generalized
      and antigen-specific immunomodulatory activities, of which the downregulation of
      endogenous immunoglobulin production is best documented. The objective of this
      study was to examine whether ingestion of colostrum altered the B cell
      subpopulations in the lymph nodes of newborn calves. Calves were fed one gallon
      of either fresh colostrum (Group A, n = 5), milk replacer (Group B, n = 5) or
      treated (frozen or irradiated) colostrum (Group D, n = 4) and were euthanized at
      36-48 h. An additional 5 calves (Group C, 3 newborn and 2 mid-term fetuses) did
      not receive any feedings; the neonatal calves were euthanized immediately
      following birth. Mesenteric and regional lymph nodes from all calves were
      analyzed by immunocytochemistry using monoclonal antibodies recognizing bovine
      IgA, IgG1, IgG2, and IgM. Calves from Groups B and C (colostrum deprived,
      neonates, and fetuses) showed a consistent pattern of IgG1 and IgG2 positive
      cells scattered individually and in clusters throughout lymph node cortex,
      paracortex, and cortico-medullary junction. In sharp contrast, no IgG1 and IgG2
      positive cells were present in the lymphoid tissues of colostrum fed calves
      (Groups A or D). Numbers of IgM and IgA positive cells were similarly distributed
      in all calf groups. These findings demonstrate that colostrum feeding reduces the
      number of immunoglobulin positive cells in the lymphoid tissues of newborn calves
      in an isotype-specific manner. This results in the elimination of IgG1 and IgG2
      positive cells that are present in both fetuses and newborn calves. This effect
      is not eliminated by freezing or irradiation, indicating that a non-cellular,
      cold-stable colostral factor is responsible. Systemically distributed colostral
      proteins such as immunoglobulin or cytokines are the most likely mediators. The
      significance of this phenomenon in terms of colostral modulation of calf
      endogenous antibody production is discussed.

PMID- 9618869
TI  - The distribution of lymphocyte subsets in normal ovine skin.
AB  - The distribution of lymphocyte subsets in the skin of clinically normal sheep was
      studied using monoclonal antibodies to OvCD5, OvCD4, OvCD8, WC1, and CD45RA. Four
      different anatomical sites were examined in each of 38 sheep. Four different age
      groups ranging from 7 to 10-day-old lambs to 12 to 14-month-old adults were
      represented. The majority of lymphocytes in all age groups and at all sites were
      angiocentrically located within the superficial dermis. Total lymphocyte numbers
      at each site increased with age. The predominant cell type identified at all
      sites was WC1+ and the proportion of lymphocytes of this phenotype was
      significantly higher at wooled sites. Only occasional CD45RA +/- cells were
      present in any section.

PMID- 9618870
TI  - Cytotoxic T lymphocyte response in chickens immunized with a recombinant fowlpox
      virus expressing Marek's disease herpesvirus glycoprotein B.
AB  - Previously, we demonstrated that cytotoxic T lymphocytes (CTLs) from MHC: B19B19
      and MHC: B21B21 chickens inoculated with a non-oncogenic Marek's disease virus
      (MDV) vaccine strain, SB-1/12 can lyse syngeneic reticuloendotheliosis virus
      (REV)-transformed cell lines expressing MDV pp38 or gB genes. In this study, we
      report the characterization of MDV gB-specific CTLs in chickens immunized with
      recombinant fowlpox virus expressing MDV gB gene (rFPV-gB). Spleen cells from
      rFPV-gB inoculated chickens (MHC: B19B19), depleted for CD4+, CD8+, TCR gamma
      delta+, TCR alpha beta 1+ or TCR alpha beta 2+ cells were used as effector cells
      in chromium release assays. Effector cells depleted of CD8+ or TCR alpha beta 1+,
      but not CD4+, TCR gamma delta+ or TCR alpha beta 2+ markedly reduced the
      percentage of specific release (%SR). Compared to the %SR caused by the SB-1/12
      sensitized CTLs, the %SR caused by rFPV-gB-sensitized CTLs was low, but
      statistically significant. This is a first report on the induction of MDV gB
      specific CD8+ CTLs in chickens immunized with rFPV-gB vaccine.

PMID- 9618872
TI  - Agriculture Committee calls for a ban on antibiotic growth promoters.

PMID- 9618871
TI  - Differential expression of adhesion molecules by chicken heterophils activated in
      vivo with Salmonella enteritidis-immune lymphokines.
AB  - Chicken heterophils activated in vivo following the intraperitoneal (i.p.)
      administration of Salmonella enteritidis-immune T lymphokines (SE-ILK) have been
      implicated in the protection against SE organ invasion. SE-ILK induces a
      heterophilia and directly (or indirectly) activates the granulocytes. The
      invasion of SE provides the secondary signal for directing activated heterophils
      to the site of bacterial invasion. We examined the mechanism of adherence within
      the avian heterophil system using an in vitro bovine serum albumin (BSA) matrix
      in which neutrophil adherence is primarily CD11/CD18 integrin mediated in
      mammalian systems. Activated heterophils displayed a four-fold increase in
      receptor-mediated adherence in vitro to BSA-coated slides as compared to control
      heterophils from PBS-injected birds. The increased adherence of activated
      heterophils can be partially blocked by either anti-alpha M (CD11b) or anti-beta
      2 (CD18) antibodies in a dose dependent manner. Anti-alpha 3 (CD49c) antibody
      partially blocked adherence of both normal and activated cells. Fluorescence
      activated cell scanning (FACS) analysis of the heterophils shows that both
      control and SE-ILK-activated heterophils collected at 4 h post injection with SE
      ILK or PBS display similar amounts of integrin alpha 3 on their surface. This
      integrin is constitutively expressed and is responsible for the in vitro
      adherence of both groups. However, antibodies to the Mac-1 complex (CD11b/CD18)
      block only the adherence of SE-ILK-stimulated heterophils. Thus, the CD11b/CD18
      heterodimer is apparently up regulated in response to the injected SE-ILK and
      plays a major role in the adherence of activated heterophils. Our studies in
      chickens parallel human and mouse studies showing the importance of the beta 2
      integrins in adherence of activated cells.

PMID- 9618873
TI  - Effects of stocking density on lambs being transported by road.
AB  - Lambs were transported for 24 hours during summer and winter at a range of
      stocking densities. Shorn lambs of mean liveweight 39.5 kg were transported at
      densities of 0.448, 0.513, 0.602 and 0.769 m2/100 kg in July and fully-fleeced
      lambs of 37.3 kg mean liveweight were transported at densities of 0.613, 0.680,
      0.775 and 0.909 m2/100 kg in February. Fewer lambs lay down and rested at high
      stocking densities and there was a marked increase in the plasma levels of
      creatine kinase at the highest stocking density in winter. All other measured
      effects of stocking density were small when compared with the overall effects of
      transport. There was a decrease in body temperature during transport, especially
      in the lambs that were recently shorn, even though they were transported during
      warm summer conditions. At the highest stocking density there was a smaller
      decrease in body temperature.

PMID- 9618874
TI  - Effect on viraemia of an American and a European serotype PRRSV vaccine after
      challenge with European wild-type strains of the virus.
AB  - Three groups of 10 pigs were vaccinated with an American serotype porcine
      reproductive and respiratory syndrome virus (PRRSV) vaccine and three groups of
      10 pigs were vaccinated with a European serotype PRRSV vaccine. A control group
      of 12 pigs was left unvaccinated. Four weeks after vaccination the PRRSV-specific
      antibody titres were determined and each group was challenged with either a
      Spanish, German or Dutch PRRSV wild-type strain. The serological responses four
      weeks after vaccination confirmed that the two vaccines were of different
      serotypes. Vaccination with the American serotype vaccine hardly reduced the
      level of viraemia after challenge with the European PRRSV wild-type strains, and
      only after challenge with the Spanish PRRSV strain was a moderate, statistically
      significant reduction in viraemia observed. In contrast, after vaccination with
      the European serotype vaccine, viraemia was completely suppressed after challenge
      with the German PRRSV isolate and almost completely suppressed after challenge
      with the Spanish and Dutch PRRSV isolates.

PMID- 9618875
TI  - Detection of Brucella species in organs of naturally infected cattle by
      polymerase chain reaction.
AB  - A polymerase chain reaction (PCR) assay was used to detect Brucella species in
      the uterus, udder, spleen, lymph nodes, kidney and liver of three cows which had
      been naturally infected in an outbreak of brucellosis, and the results were
      compared with the results of bacteriological investigations. All 18 samples
      reacted positively in the PCR, but five samples had weak bands after the
      electrophoretic separation of PCR mixtures. No Brucella strains could be detected
      in these five samples by bacterial cultivation, but all the other samples gave
      positive results. A pre-enrichment procedure was necessary for the PCR. A PCR
      with DNA from eight Yersinia strains gave no amplification product.

PMID- 9618876
TI  - Spinal arachnoid cysts in two shih tzu littermates.
AB  - Progressive ataxia and quadriparesis in two shih tzu littermates was found to be
      caused by almost identical, cranial cervical, spinal arachnoid cysts. The cysts
      were treated surgically by dural marsupialization via a dorsal laminectomy. One
      pup recovered uneventfully and remains clinically normal more than a year after
      surgery. The second pup made a slow and incomplete recovery before the signs
      worsened, necessitating euthanasia. Postmortem examination showed no evidence of
      the re-formation of the cyst.

PMID- 9618878
TI  - Mastitis incidence in straw yards and cubicles.

PMID- 9618877
TI  - Elimination of Mycoplasma bovis mastitis from an Irish dairy herd.

PMID- 9618879
TI  - Outbreak of tetanus in lambs.

PMID- 9618880
TI  - Clinically silent rabies infection in (zoo) bats.

PMID- 9618881
TI  - First report of bovine neosporosis in dairy cattle in Costa Rica.

PMID- 9618882
TI  - Population density and infectious disease at bird tables.

PMID- 9618883
TI  - Severe oral ulceration in lambs.

PMID- 9618884
TI  - Funding veterinary education.

PMID- 9618885
TI  - Unusual ocular condition in Burmese cats.

PMID- 9618886
TI  - Stimulation of the bronchus-associated lymphoid tissue of goats and its effect on
      in vitro colonization by Pasteurella haemolytica.
AB  - Twenty goats of about 7 months of age were divided into five groups. The goats in
      groups 1 and 2 were exposed once, using an intranasal spray to 2 ml of an
      inoculum containing 10(6) colony-forming units/ml of living or dead Pasteurella
      haemolytica A2, respectively. The goats in groups 3 and 4 were similarly exposed
      twice at a 2-week interval. Group 5 was the untreated control. The number and
      size of the bronchus-associated lymphoid tissue (BALT) in goats exposed twice to
      either living or dead organisms were significantly (p < 0.05) increased compared
      with those exposed once and with the unexposed control. In vitro colonization by
      living P. haemolytica A2 onto the lung tissue in which the BALT had been
      stimulated by two exposures of either living or dead organisms was significantly
      (p < 0.05) reduced. The study indicates that stimulation of the respiratory
      mucosal immunity may prevent P. haemolytica A2 infection.

PMID- 9618887
TI  - The pathogenicity and pathogenesis of Mycoplasma capricolum subsp.
      capripneumoniae (F38) in the caprine mammary gland.
AB  - The right mammary gland of 12 lactating goats was inoculated intracisternally
      with 1 ml of Mycoplasma capricolum subsp. capripneumoniae (Mcc) containing 10(6)
      colony-forming units (CFU), while their left mammary halves received 1 ml of
      sterile PPLO broth only. Two goats served as uninfected controls. The clinical
      mastitis that developed in the infected mammary halves within 24 h was initially
      acute but became increasingly chronic by the end of the experiment at 24 days
      post inoculation (DPI). The disease was characterized by atrophy of the infected
      mammary halves, leading to marked agalactia and an increase in somatic cell
      counts, with a preponderance of neutrophils initially and lymphocytes later. The
      Mycoplasma was re-isolated from infected mammary secretions up to 16 DPI but not
      from blood. Histopathology revealed that the mastitis was acute and purulent
      initially, followed by infiltration of lymphonuclear cells and fibroplasia in the
      lymphomononuclear cells and fibroplasia in the interacinar tissue, and later by
      massive fibrosis. Immunohistology demonstrated the presence of Mycoplasma-like
      bodies localized mainly on the surface of acinar/duct epithelial cells. The
      studies showed that Mcc was highly pathogenic in the caprine mammary gland.

PMID- 9618889
TI  - Validation of a commercially available enzyme-linked immunosorbent assay (ELISA)
      for the determination of cortisol in canine plasma samples.
AB  - Samples were obtained from clinically normal dogs before and after ACTH
      stimulation and dexamethasone suppression tests. The test kit Enzymun-Test
      (Boehringer Mannheim) for determining cortisol concentrations in human plasma was
      used in connection with the analyser system Enzymun-Test (Boehringer Mannheim)
      System ES300 following the manufacturer's instructions. The intra-assay and inter
      assay coefficients of variation were 1.28% and 5.64%, respectively. The mean
      recovery when assaying samples with a cortisol content of more than 100 nmol/L
      was 95.41%, but this percentage decreased in samples with lower cortisol levels.
      The sensitivity of the assay was 2.76 nmol/L. The results of the ACTH stimulation
      and dexamethasone suppression tests were similar to those published previously.
      The ELISA method evaluated allows a precise and sensitive determination of
      cortisol concentrations in canine plasma samples. The major drawback observed was
      the loss of accuracy at low cortisol concentrations. Since the assay tends then
      to report lower cortisol concentrations, the generally accepted concentration of
      40 nmol/L may not be suitable as the cutoff value in dexamethasone suppression
      tests.

PMID- 9618888
TI  - An evaluation of serum fructosamine as a marker of the duration of
      hypoproteinaemic conditions in dogs.
AB  - Serum samples were collected from 153 normoglycaemic, hypoproteinaemic dogs of
      known case histories, and assayed for fructosamine, glucose, total protein and
      albumin concentrations. This study was conducted to evaluate the relationship
      between serum fructosamine and total serum proteins, or more specifically serum
      albumin. Serum fructosamine was positively correlated with both total serum
      protein (r = 0.47, p < 0.00001) and serum albumin (r = 0.77, p < 0.00001). Mean
      serum albumin concentrations were significantly different when the data were
      grouped as dogs with normal versus subnormal serum fructosamine concentrations.
      The data indicate the value of the serum fructosamine assay in estimating the
      duration of hypoalbuminaemia. Concurrent hypoalbuminaemia and normal serum
      fructosamine indicate hypoalbuminaemia of less than one week. Concurrent
      hypoalbuminaemia and hypofructosaminaemia indicate persistent hypoalbuminaemia of
      more than one week, and concurrent normal albumin and hypofructosaminaemia
      indicate recovery from a condition including hypoalbuminaemia or hypoglycaemia.

PMID- 9618890
TI  - A comparison of the activities of certain enzymes related to energy metabolism in
      leukocytes in dogs and cats.
AB  - The activities of Na+,K(+)-ATPase in plasma membrane, of cytosolic enzymes and of
      glutamate dehydrogenase (GlGD) in mitochondria were measured in leukocytes (WBC)
      from dogs and cats to clarify the differences in energy metabolism in these
      cells. Feline WBC had significantly higher activities of hexokinase (HK),
      pyruvate kinase (PK) and LDH with pyruvate as substrate than did canine WBC.
      Canine WBC had significantly higher activities of glucokinase (GK) and GlDH than
      did feline WBC. Feline WBC had unique characteristics of energy metabolism in
      that the activities of the cytosolic enzymes under anaerobic conditions were
      significantly higher than those in canine WBC. It therefore appears that there
      are distinct differences in glucose-metabolism in WBC between dogs and cats. WBC
      enzyme activities are considered to reflect the metabolic state in the whole body
      of the animal. It is therefore suggested that changes in the activities of
      certain glycolytic enzymes in WBC may be useful as a diagnostic indicator in some
      types of metabolic disease in dogs and cats.

PMID- 9618892
TI  - A preliminary study of the pharmacokinetics of fenoprofen enantiomers following
      intravenous administration of the racemate to cats.

PMID- 9618891
TI  - Immunological determination of faecal haemoglobin concentrations in dogs.
AB  - Faecal haemoglobin (Hb) concentrations in apparently healthy experimental Beagle
      dogs and in dogs of various breeds kept in private households or at breeders were
      measured by reversed passive latex agglutination (RPLA) and enzyme-linked
      immunosorbent assay (ELISA) in an effort to define the physiological
      concentrations of faecal Hb in the dog. In 88% (53) of 60 experimental Beagle
      dogs (30 males and 30 females), the RPLA titres were 1:2 and 1:8 and the faecal
      Hb concentrations ranged from 40.0 to 431.5 (mean 184.1 +/- 92.6) micrograms/g
      faeces by ELISA. No significant difference was found in Hb levels or RPLA titres
      between males and females. Seven dogs (12%) had significantly greater RPLA titres
      and Hb concentrations by ELISA than the remaining dogs. In 84% (45) of the 53
      dogs kept in private households or at breeders, the RPLA titres were < 1:1 to 1:8
      and the faecal Hb concentrations ranged from 7.1 to 456.7 (mean 137.5 +/- 128.7)
      micrograms/g faeces in ELISA. Eight of these dogs (15.1% of 53 dogs) had
      significantly greater RPLA titres and Hb concentrations by ELISA than the
      remaining dogs. There were no significant differences between the Beagles and
      dogs kept in private households or at breeders. In conclusion, in 98 (86.7% of
      113) dogs the physiological concentrations of RPLA titres were < 1:1 to 1:8 and
      the faecal Hb concentrations were 143.5-185.1 micrograms/g (95% confidence
      level). Approximately 13.3% of apparently healthy dogs had higher faecal Hb
      concentrations, suggesting the presence of subclinical haemorrhages. Four dogs
      suffering from colorectal cancer also had high faecal Hb concentrations.

PMID- 9618894
TI  - [Prevention of cardiovascular diseases: Value of CSE inhibitors in the management
      of lipid metabolism disorders].

PMID- 9618893
TI  - PCR studies on the potential sites for latency of BHV-4 in calves.
AB  - The aim of the study was to examine various tissues of experimentally infected
      calves for the BHV-4 genome so as to detect in which cells the virus persists
      during the latent phase of the infection. The presence of the bovine herpesvirus
      type 4 genome was detected by a nested PCR in a variety of tissues collected from
      two susceptible calves experimentally infected 62 days earlier. Mild clinical
      signs of bronchitis, an elevated body temperature for 2-3 days, and a slightly
      increased number of blood leukocytes were observed in both inoculated calves. BHV
      4 was demonstrated in seven samples from the 12 different parts of the nervous
      system tested from each calf (29.1%), from the cornea, from lymph nodes near to
      the inoculation site, from the gallbladder and from the bone marrow. Thus a
      member of the predominantly lymphotropic Gammaherpesvirinae subfamily was
      detected in neural tissue and other organs that have never been associated with
      persistence.

PMID- 9618895
TI  - [Coronary mortality lowered by 24%. Convincing results of the LIPID Study on
      Secondary Prevention].

PMID- 9618896
TI  - [Value of fluorides in the treatment of osteoporosis. Munchen, 15-16 January
      1998].

PMID- 9618897
TI  - [Tracing complex processes of cartilage metabolism. International Symposium "From
      Cartilage Metabolism to Clinics--from cartilage metabolism to therapy". Berlin,
      10-11 October 1997].

PMID- 9618898
TI  - Rhythmic transcription: the molecular basis of circadian melatonin synthesis.
AB  - Adaptation to a changing environment is an essential feature of physiological
      regulation. The day/night rhythm is translated into hormonal oscillations
      governing the physiology of all living organisms. In mammals the pineal gland is
      responsible for the synthesis of the hormone melatonin in response to signals
      originating from the endogenous clock located in the hypothalamic suprachiasmatic
      nucleus (SCN). The molecular mechanisms involved in rhythmic synthesis of
      melatonin involve the CREM gene, which encodes transcription factors responsive
      to activation of the cAMP signalling pathway. The CREM product, ICER, is
      rhythmically expressed and participates in a transcriptional autoregulatory loop
      which also controls the amplitude of oscillations of serotonin N-acetyl
      transferase (AANAT), the rate-limiting enzyme of melatonin synthesis. In
      contrast, chick pinealocytes possess an endogenous circadian pacemaker which
      directs AANAT rhythmic expression. cAMP-responsive activator transcription
      factors CREB and ATF1 and the repressor ICER are highly conserved in the chick
      with the notable exception of ATF1 that possesses two glutamine-rich domains in
      contrast to the single domain encountered to date in mammalian systems. ICER is
      cAMP inducible and undergoes a characteristic day-night oscillation in expression
      reminiscent of AA-NAT, but with a peak towards the end of the night.
      Interestingly CREB appears to be phosphorylated constitutively with a transient
      fall occurring at the beginning of the night. Thus, a transcription factor
      modulates the oscillatory levels of a hormone.

PMID- 9618899
TI  - Non-photic signalling in the suprachiasmatic nucleus.
AB  - Scheduled arousal by handling and sub-cutaneous saline injection entrains the
      free-running clock of the adult Syrian hamster and outbred (ID(ICR)) but not
      inbred (C57B16) mice. Syrian hamsters bearing lesions of the intergeniculate
      leaflet of the thalamus remain able to entrain and phase-shift to light, but the
      lesions block completely entrainment by serial arousal, even though lesioned
      animals continue to respond acutely to the arousing cue. This suggests that the
      innervation from the IGL to the SCN is a necessary component of the pathways
      which signal an aroused state to the clock. Siberian hamsters do not entrain to
      serial arousal but they do entrain to serial injections of melatonin, whereas in
      adult Syrian hamster, systemic treatment with melatonin has no effect above that
      of arousal. In contrast to the adult, the foetal and neonatal Syrian hamster can
      be entrained by melatonin. These variations in sensitivity correlate with inter
      specific and developmental differences in the pattern and level of expression of
      melatonin receptors in the SCN. The perinatal hamster can also be entrained by
      dopaminergic agonists. SCN tissue from neonatal Syrian hamsters was used to
      characterise the biochemical actions of dopamine and melatonin. In primary
      culture and tissue explants, forskolin, dopamine and glutamatergic agonists all
      stimulated the phosphorylation of the transcription factor CREB. This probably
      occurred via convergent actions through Ca2+ (glutamate) and cyclic AMP-dependent
      (forskolin, dopamine) signalling pathways. Dopamine induced phospho-CREB-ir
      exclusively in GABA-ir neurons and melatonin reversed this effect of dopamine,
      indicative of an inhibitory Gi protein linking via the Mel1a receptor to adenylyl
      cyclase. The regulation of phospho-CREB by multiple entraining cues in the SCN
      highlights its position as a point of convergence for regulators of the clock,
      and indicates a possible role in entrainment.

PMID- 9618900
TI  - Control of CREB phosphorylation and its role for induction of melatonin synthesis
      in rat pinealocytes.
AB  - Phosphorylation of the transcription factor CREB appears as an important step in
      the signal transduction cascade that activates melatonin biosynthesis in the
      mammalian pineal organ. We have studied the mechanisms causing CREB
      phosphorylation by immunocytochemical and immunochemical demonstration of
      phosphorylated CREB (pCREB) in isolated, immunocytochemically identified rat
      pinealocytes kept in vitro and in the rat pineal organ in situ. Norepinephrine
      (NE), the most potent stimulator of the melatonin biosynthesis was shown to
      induce pCREB immunoreaction (i.r.) in the vast majority of pinealocytes in a time
      and dose-dependent manner. This response was elicited by stimulation of beta
      adrenergic receptors resulting in an increase in the intracellular cAMP
      concentration. Activation of alpha 1-adrenergic receptors that causes a rise in
      intracellular calcium via stimulation of intracellular stores and subsequent
      increase in calcium influx did not evoke pCREB ir on its own and did not
      potentiate the beta-adrenergic response. VIP and PACAP that activate the
      melatonin biosynthesis to a lesser extent than NE induced pCREB ir in only 50-60%
      of the pinealocytes. Immunoblotting showed that a protein of 43 kDa corresponding
      to CREB accounts for the pCREB ir and confirmed that VIP and PACAP are less
      effective in inducing CREB phosphorylation than NE. The amount of total
      (phosphorylated and unphosphorylated) CREB was not changed upon stimulation of
      the cells with NE, VIP or PACAP. In an attempt to identify the protein kinase
      catalyzing CREB phosphorylation in rat pinealocytes, the cAMP-dependent protein
      kinases (cAK) present in the rat pineal were identified with the use of
      antibodies recognizing different catalytic and regulatory subunits. Application
      of cAK agonists and antagonists showed that the cAK type II is responsible for
      CREB phosphorylation. Correlations between the melatonin concentration in the
      medium and the CREB phosphorylation in pinealocytes revealed a tight connection
      between these two parameters. Phosphorylation of CREB appears important for the
      stimulation of melatonin biosynthesis also under natural conditions because our
      investigations of whole pineal organs taken from rats during different time
      points of the 24 h light-dark cycle revealed a strong induction of pCREB ir in
      the first part of the night.

PMID- 9618902
TI  - Beta-adrenergic signal transduction in the hypothalamus of the European hamster:
      relation with the seasonal hibernation cycle and the diurnal activity cycle.
AB  - Mammalian hibernation, an adaptation to survive harsh winter conditions, is one
      of the most prominent seasonal rhythmic processes exactly regulated on a low
      metabolic level. Diurnal variations in vegetative physiology are missing during
      hibernation; however, a precisely working diurnal system is mandatory for both
      the proper initiation and termination of the annual hibernation phase and the
      periodical arousal reactions. Biorhythms and the vegetative physiological
      processes connected with hibernation are, among others, controlled by
      hypothalamic noradrenaline systems. In this study, the density, binding capacity,
      and relative proportions of beta 1- and beta 2-adrenergic receptors (AR) within
      the hypothalamus of: 1) motorically inactive summer; 2) motorically active
      summer; 3) aroused, motorically active winter; and 4) deeply hibernating winter
      European hamsters (Cricetus cricetus) were studied. For further analysis of the
      beta-adrenergic signal transduction cascade, the activity of adenylyl cyclase
      (AC) was measured by formation of cAMP in controls, after stimulation of G
      proteins, or after forskolin stimulation without or in presence of manganese
      ions. While beta 1- and beta 2-AR subtypes were nearly equally abundant (50% beta
      1:50% beta 2) in active summer, inactive summer, and hibernating hamsters, a
      significant redistribution in favor of beta 2-AR occurred after arousal (40% beta
      1:60% beta 2). The activity of AC was much higher in active summer hamsters than
      in inactive summer, aroused winter, and hibernating winter hamsters. When AC was
      stimulated by guanylylimidophosphate [Gpp(NH)p], MnCl2, forskolin, or by
      forskolin in presence of MnCl2 instead of MgCl2, the potency to stimulate AC was
      found to show the following rank order: basal < Gpp(NH)p < MnCl2 < or = forskolin
      + MnCl2 < forskolin.

PMID- 9618901
TI  - Serotonergic innervation of the hypothalamic suprachiasmatic nucleus and photic
      regulation of circadian rhythms.
AB  - Converging lines of evidence have firmly established that the hypothalamic
      suprachiasmatic nucleus (SCN) is a light-entrainable circadian oscillator in
      mammals, critically important for the expression of behavioral and physiological
      circadian rhythms. Photic information essential for the daily phase resetting of
      the SCN circadian clock is conveyed directly to the SCN from retinal ganglion
      cells via the retinohypothalamic tract. The SCN also receives a dense
      serotonergic innervation arising from the mesencephalic raphe. The terminal
      fields of retinal and serotonergic afferents within the SCN are co-extensive, and
      serotonergic agonists can modify the response of the SCN circadian oscillator to
      light. However, the functional organization and subcellular localization of 5HT
      receptor subtypes in the SCN are just beginning to be clarified. This information
      is necessary to understand the role 5HT afferents play in modulating photic input
      to the SCN. In this paper, we review evidence suggesting that the serotonergic
      modulation of retinohypothalamic neurotransmission may be achieved via at least
      two different cellular mechanisms: 1) a postsynaptic mechanism mediated via 5HT1A
      or 5ht7 receptors located on SCN neurons; and 2) a presynaptic mechanism mediated
      via 5HT1B receptors located on retinal axon terminals in the SCN. Activation of
      either of these 5HT receptor mechanisms in the SCN by specific 5HT agonists
      inhibits the effects of light on circadian function. We hypothesize that 5HT
      modulation of photic input to the SCN may serve to set the gain of the SCN
      circadian system to light.

PMID- 9618904
TI  - Current theories of neuronal information processing performed by Ca2+/calmodulin
      dependent protein kinase II with support and insights from computer modelling and
      simulation.
AB  - Ca2+/calmodulin-dependent protein kinase II (CaMKII) is concentrated in brain,
      and is particularly enriched in synaptic structures where it comprises 20-50% of
      all proteins. The abundant nature of CaMKII and its ability to phosphorylate a
      wide range of substrate proteins, including itself, earmarks it as a protein
      kinase that may have a vital role in neuronal information processing and memory.
      A computer model of CaMKII is investigated that incorporates recent findings
      about the geometrical arrangement of subunits, the mechanism of Ca(2+)-dependent
      subunit activation, and Ca(2+)-independent autophosphorylation. The model is
      framed as a system of nonlinear differential equations. It is demonstrated
      numerically that (1) CaMKII is tuned to be activated by stimulation protocols
      associated with the induction of long-term potentiation; (2) the observed slow
      dissociation of trapped Ca2+/calmodulin may require the autonomy site to be
      protected from dephosphorylation; and (3) Ca(2+)-independent kinase activity is
      expressed in a manner akin to a graded switch. The model validates current
      theories concerning how CaMKII may be a Ca2+ pulse frequency detector, a
      molecular switch, or a mediator of the threshold for long-term synaptic
      plasticity.

PMID- 9618903
TI  - Melatonin receptor pharmacology: toward subtype specificity.
AB  - The recent cloning of three distinct melatonin receptor subtypes (Mel1a, Mel1b
      and Mel1c) which are part of a new family of G-protein coupled receptors, and
      probably mediate the physiological actions of the hormone, has spurred interest
      in the design of analogues with subtype selectivity. The 5-methoxyl and N-acetyl
      groups of melatonin are important for binding to and activation of the receptor.
      The indole nucleus serves to hold these two groups at the correct distance from
      one another and allows them to adopt the required orientation for interaction
      with the receptor binding pocket. We have investigated the subtype selectivity of
      a number of analogues of melatonin in which the structure has systematically been
      modified in order to probe the similarities and differences in the interaction of
      ligand and receptor subtype. At all three subtypes 5-methoxyl and N-acetyl groups
      of melatonin are important for high affinity binding. However, replacing the 5
      methoxyl group (eg with 5-H, 5-OH, 5-Me or 5-BzO) reduces affinity much less at
      the Mel1b receptor subtype than at either Mel1a or Mel1c cloned subtypes. This
      suggests differences between the Mel1b and Mel1a/1c subtypes in the size and
      shape of the binding pocket or in the manner in which melatonin interacts with
      the receptor at this position. Further studies have revealed that analogues with
      longer N-acyl carbon chains behave similarly at each subtype. These observations
      suggest that the 'pocket' into which the N-acetyl group fits is very similar for
      each subtype. Substitutions at the 2-position on the indole ring improved
      affinity at each receptor subtype but did not give selective analogues. The
      systematic 'mapping' of the requirements for binding at each receptor subtype
      should allow the design of more selective agonists and antagonists, which will be
      valuable tools for the characterization and classification of functional
      melatonin receptors.

PMID- 9618905
TI  - Death during deliberate propane inhalation.
AB  - Propane gas is used as a fuel and very rarely it is abused by young people in
      Greece. In this paper, we report a case of abuse of propane inhalation that
      resulted in accidental death. The determination of propane in autopsy samples was
      done by headspace gas chromatography and semiquantitation in liver, blood and the
      contents of the plastic bag through which the gas was diffused, which proved to
      be lethal.

PMID- 9618906
TI  - Detection of bathsalts in the lungs of a baby drowned in a bathtub: a case
      report.
AB  - This case is one in which a baby was found dead, apparently drowned in a bathtub.
      To confirm the inhalation of bathwater, an extract taken from the baby's lungs
      was analyzed with high-performance liquid chromatography. Bathsalts contained in
      the bathwater were detected in the extract. Bathsalts are usually used in home
      bathtubs and, as a dye material, they contain fluorescein which is highly
      sensitive to detection. The presence of fluorescein in the lung tissue and in the
      other tissues greatly helps to confirm the bathwater drowning.

PMID- 9618907
TI  - Intra-cartilaginous laryngeal haemorrhages and strangulation.
AB  - A previously unrecognized laryngeal injury in young female victims of manual
      strangulation is described. Twelve larynges that were retrospectively and
      prospectively collected at the Office of the Chief Coroner for Ontario (1982
      1997) were used for this study. In all instances, the larynges were from cases of
      strangulation (mean age 27 +/- 10 years, range 20-46) with classical postmortem
      findings of asphyxia and either manual or combined manual and ligature
      strangulation. None of the larynges had fractures of the lamina of the thyroid
      cartilage, superior cornua, or cricoid cartilages. However, in 9 of the 12 cases
      (75%), sagittal sections revealed multifocal acute haemorrhages into the base of
      the superior cornua of the thyroid cartilage at the point of origin from the
      laminae. The presence of acute intra-cartilaginous haemorrhage into the larynx
      likely represents the disruption of small blood vessels due to elastic
      deformation of the flexible larynx during strangulation. The recognition of this
      form of laryngeal injuries broadens the pathological findings in cases of
      asphyxia associated with pressure on the neck.

PMID- 9618908
TI  - Homicidal and suicidal sharp force fatalities in Stockholm, Sweden. Orientation
      of entrance wounds in stabs gives information in the classification.
AB  - A comparative study of 174 homicidal and 105 suicidal sharp force deaths in the
      Stockholm area is presented in order to identify variables of importance in the
      differentiation between homicides and suicides. In homicides, a significantly (p
      < 0.05) higher number of cut and stab wounds were seen in the head, upper and
      lower extremities and a significantly higher number of vertical stab wounds were
      found in the chest. Lower numbers were seen in the wrist and the crook of the
      arm. When counting the injured areas, irrespective of the number of injuries,
      abdominal wounds and horizontal chest stab wounds were also significantly more
      often found in victims of homicide. Injuries to the back and to the genitals were
      not seen in suicides. The suicide victims were significantly older and had
      significantly lower blood alcohol levels. A new variable pointing at a
      statistically significant difference between homicides and suicides was found: In
      homicides, stab wounds with a horizontal axis of entrance wound in the chest was
      found to be less common than those with a vertical axis. Other variables studied
      were prevalence of defence and tentative wounds, farewell notes and suicidal
      ideation, earlier parasuicides, venue, gender of the victims and the types of
      sharp objects used.

PMID- 9618909
TI  - Fatal falls from a height: the use of mathematical models to estimate the height
      of fall from the injuries sustained.
AB  - The authors undertook a review of fatal falls from a height, that occurred in
      1991-92 in Singapore, with the objective of constructing mathematical models
      relating the height of fall to the injuries sustained. The 603 cases studied
      showed a mean age of 41.4 years with a male to female ratio of approximately 2:1.
      A sub-sample of 416 (69%) of these subjects had fallen from known heights (mean,
      26.9 m; range, 3-69.6 m) and were studied in further detail. Bivariate analysis
      of this group showed that their injury severity score (ISS) was significantly
      correlated with the height of fall (H) and age (P < 0.01; r = 0.412 and 0.187,
      respectively). As the ISS is not strictly a continuous variable and varied
      markedly with H, it was categorised into bands (ISSB) before being subjected to
      further analysis. Regression modelling to adjust for mutual confounding showed
      that both height of fall and age were significant independent determinants of the
      ISSB (P < 0.0001). A model with H as the dependent variable was then constructed
      to relate the height of fall to ISSB and other statistically significant
      indicators of the extent and the severity of the injuries sustained. A second
      model with bands of height (HB) as the dependent variable was similarly
      constructed to assess the effect of banding both height and ISS. Our findings
      suggested that the height of fall was significantly associated with age, ISS and
      the extent of injury (mostly AIS > or = 3), and confirmed the usefulness of these
      models for investigative purposes. Statistical models could be designed and used
      to assess any apparent discrepancy between injury severity as determined at
      autopsy and the suspected/alleged height of fall.

PMID- 9618910
TI  - Analysis of beveling in gunshot entrance wounds.
AB  - The analysis of skeletal trauma is an important aspect of forensic case work. Yet
      most major pathology references devote limited attention to this topic. The aim
      of this paper is to analyze beveling in gunshot entrance wounds, from a series of
      27 cases with a total of 39 wounds. Assessment was made by measuring the external
      and internal cranial dimensions, describing the area of most pronounced beveling,
      and correlating the directions of the beveling with the trajectory of the bullet.
      Results indicated that inward beveling was found in 36 of 39 cases, the absence
      of beveling in four bones, and actual external beveling in one case. The
      inconsistency in the direction of most pronounced beveling in reference to the
      direction of shooting leads to the conclusion that this characteristic cannot be
      used to make a reliable assessment of the direction of fire.

PMID- 9618911
TI  - On the phenomenology of lethal applications of insulin.
AB  - This study deals with the postmortem findings in cases of lethal hypoglycaemia
      due to injections of insulin. In 12 cases (four female; eight male; mean age 42
      years) the following aspects were evaluated retrospectively: circumstances of
      life, scene of death, pathomorphological findings and postmortem biochemistry on
      cerebrospinal fluid, vitreous humour, blood, and urine (levels of glucose,
      lactate, hemoglobin A1C and insulin). Furthermore, analyses of ethanol in blood
      and urine as well as toxicological and histological examinations were performed.
      Unexpectedly, the dead persons rarely represented diabetics, relatives of
      diabetics, or medical personnel. It is concluded, that the diagnosis of fatal
      hypoglycaemia can only be established by a synopsis of postmortem biochemistry,
      pathomorphological alterations and anamnesis. Besides, this diagnosis must always
      be made "per exclusionem".

PMID- 9618912
TI  - Mitochondrial DNA polymorphism in populations of Siberian and European roe deer
      (Capreolus pygargus and C. capreolus).
AB  - We have amplified and sequenced 679 nucleotides of the mitochondrial DNA control
      region in 45 Siberian (Capreolus pygargus) and European (C. capreolus) roe deer
      from two localities in Russia and seven in Italy. Average interspecific sequence
      divergence was 4.9%. Six different haplotypes were found in Siberian roe deer,
      and 14 haplotypes in Alpine European roe deer. A population of the endemic
      Italian subspecies C. c. italicus was monomorphic bearing a single haplotype with
      one unique nucleotide deletion and a fixed transversion. Phylogenetic
      relationships among haplotypes indicated that the two species were separated with
      100% bootstrap support, and there were two distinct population clusters within
      each species. These clusters correspond to different geographical locations of
      the samples: Siberian roe deer were subdivided into west Siberia (Kurgan region)
      and east Siberia (Amur region), and European roe deer were subdivided into an
      eastern and a western Alpine group. Average sequence divergence among conspecific
      populations was 1.2%. Calibrations of evolutionary rates of the different domains
      of the control-region suggest that Siberian and European roe deer speciated about
      2-3 million years ago, and haplotype diversity within species was generated
      during the last 150,000-370,000 years. Geographical structuring of sequence
      variability in roe deer allows us to identify historical and recent intraspecific
      population differences, including the effects of human disturbance. The genetic
      peculiarities of the endemic Italian subspecies C. c. italicus call for careful
      conservation of its surviving populations.

PMID- 9618913
TI  - Efficiency of multistage marker-assisted selection in the improvement of multiple
      quantitative traits.
AB  - The application of marker-assisted selection (MAS) to breeding programmes depends
      on its relative cost and the expected economic return compared to conventional
      phenotypic selection. The relative efficiency of MAS can be increased through a
      two-stage selection scheme or through marker-based, multiple-trait improvement.
      However, the effectiveness of these alternatives has not been quantified. In this
      study, we evaluate the efficiency of MAS relative to conventional phenotypic
      selection and marker-only selection in multistage selection for the improvement
      of multiple traits. We further incorporate the costs of obtaining measurements on
      phenotypic characters and marker loci into the objective function to evaluate the
      efficiency of MAS with respect to the gain per unit cost. Deterministic analyses
      indicate that excluding costs, multiple-trait MAS can be used to increase the
      aggregate breeding values in quantitative characters and is expected to be more
      effective than conventional selection or single-trait MAS. Two-stage MAS has a
      slightly reduced gain because of culling in the first stage. If the objective
      function is to maximize the gain per unit cost, multiple-trait MAS is inferior to
      phenotypic selection in most of the selection schemes investigated when the cost
      ratio (r) of obtaining measurements on phenotypic characters to scoring marker
      loci is less than unity (r < or = 1.0) and the heritability (h2) is greater than
      0.3. The efficiency of MAS increases as r increases and h2 decreases. For MAS to
      be more effective, it is necessary to decrease further the cost associated with
      molecular marker assays.

PMID- 9618914
TI  - Quantitative trait loci for fluctuating asymmetry of discrete skeletal characters
      in mice.
AB  - Levels of fluctuating asymmetry (FA) are often taken as indicators of the degree
      to which genotypes differ in their ability to buffer genetic and environmental
      sources of variation. Interval mapping techniques were used to search for
      quantitative trait loci (QTLs) affecting directional asymmetry (DA) and
      fluctuating asymmetry (FA) in six bilateral discrete skeletal traits in house
      mice. These six characters as well as 76 microsatellite markers were scored in
      over 500 mice that resulted from crosses of F1 mice originally produced from
      matings of the Large (LG/J) and Small (SM/J) inbred strains. The number of QTLs
      affecting DA in each of the characters was no more than expected by chance alone
      so it was concluded that there was little evidence for individual genes affecting
      DA. There appeared to be a genetical basis for FA in these characters, however,
      because the number of QTLs significantly affecting FA (10 at the 5% level, three
      at the 1% level) was greater than expected by chance alone. The 10 QTLs
      significantly affecting FA in any given character were located on eight different
      chromosomes, mostly at locations for QTLs affecting other characters or DA in
      other characters. Their cumulative contribution to the total phenotypic variance
      was small, averaging only 3.9% per locus. Dominance genotypic values for these
      QTLs were more extreme than additive genotypic values, suggesting that
      heterozygotes at many loci are better buffered than homozygotes and that allelic
      interactions (dominance) may play an important role in the production of FA.

PMID- 9618915
TI  - Absorbance detection of amino acids by laser wave mixing in microbore liquid
      chromatography.
AB  - Nonlinear optical phase conjugation by degenerate four-wave mixing is
      demonstrated as a sensitive "absorbance" detection method for microbore high
      performance liquid chromatography. An argon ion laser operating at the 488-nm
      line is used as the excitation light source to generate the wave-mixing signal
      for dabsyl-labeled amino acids. Advantages of the nonlinear laser detection
      method include: virtually 100% optical signal collection efficiency, generation
      of the signal in the form of a coherent laser beam, signal measurement against a
      virtually dark background, reliable detection of small absorbance values,
      excellent detection sensitivity for both fluorescing and non-fluorescing
      analytes, relatively simple one-color one-laser optical setup, and low power or
      energy requirements for continuous-wave or pulsed lasers. Using our one-laser one
      color nonlinear laser detector for "absorbance" measurements in liquid
      chromatography, we report a crude preliminary "injected" detection limit of 780
      fmol for glycine.

PMID- 9618916
TI  - n-alkyl fluorenyl phases in chromatography. I. Synthesis and characterization.
AB  - A new class of silica gel-bound fluorene phases is described. The compounds are
      synthesized via reaction of fluorenyl lithium with omega-alkenyl bromides leading
      to 9-(5'-hexenyl)-9H- and 9-(9'-decenyl)-9H-fluorene (1 and 2), followed by
      hydrosilation reactions with different hydrosilanes. The resulting omega
      functionalized silylalkyl fluorenes 3a(T0), 3b(T0), 4a(T0), 4b(T0) and 4c(M0)
      (Scheme 1) react with surface silanol groups of silica gel to generate the new
      fluorene phases 3a(Tn)(Qm)y, 3b(Tn)(Qm)y, 4a(Tn)(Qm)y, 4b(Tn)(Qm)y and
      4c(M1)(Qm)y. The phases are characterized by employing 1H, 13C and 29Si solid
      state nuclear magnetic resonance spectroscopy. Their applicability in high
      performance liquid chromatography is proved by the Sander and Wise test (SRM
      869). In contrast to conventional n-alkyl phases, pi-pi interactions are
      additionally involved in the separation process and, therefore, the retention
      times of the polycyclic aromatic hydrocarbons sample molecules depend on the
      ligand densities of the applied fluorene phases.

PMID- 9618917
TI  - Identification of pesticides by liquid chromatography--particle beam mass
      spectrometry using electron ionization and chemical ionization.
AB  - Liquid chromatography-mass spectrometry (LC-MS) with a particle beam (PB)
      interface is used to separate and identify a group of pesticides. The mass
      spectra obtained under the different ionization modes, electron ionization (EI)
      and positive and negative chemical ionization (PCI and NCI) are compared. The
      operating conditions under each mode, determined by studying the influence on the
      ion abundance of the ion source temperature of the EI mode, and the gas pressure
      and ion source temperature in the methane CI were optimized. EI was more
      sensitive than PCI and NCI and of the latter two modes, NCI gave higher
      responses, especially for organophosphorus compounds. When on-line solid-phase
      extraction-LC-PB-MS was applied to real samples, limits of detection in full scan
      mode were in the range of 0.5 and 10 micrograms l-1 for EI. The analysis of real
      samples by on-line solid-phase extraction-LC-PB-MS enabled EI detection of one of
      the pesticides studied and confirmation by PCI and NCI. The combined EI/CI
      information also enabled the detection of some non-target compounds.

PMID- 9618918
TI  - Method for determining the content of catechins in tea infusions by high
      performance liquid chromatography.
AB  - A high-performance liquid chromatography method employing diode array detection
      was developed to determine levels of the major catechins present in black, green,
      and Jasmine tea infusions. Reversed-phase separations were performed on a C18
      column using three gradients: acetonitrile-acetate buffer, methanol-acetate
      buffer, and acetonitrile-acetate buffer with ascorbic acid. The identities of the
      tea catechins were established by comparing absorbance spectra and retention
      times to reference standards chromatographed under identical conditions.
      Epicatechin, epigallocatechin, epicatechin gallate, and epigallocatechin gallate
      were found in all the tea infusions examined, ranging in concentration from 1-13
      mg dl-1. These levels indicate that even moderate tea consumption can contribute
      a substantial quantity of flavanols to the diet. Although some differences
      between the three brewed teas were evident, all were comparably good sources of
      these catechins.

PMID- 9618919
TI  - Rapid and sensitive liquid chromatographic method using a conductivity detector
      for the determination of phytic acid in food.
AB  - An LC method was developed for the determination of phytic acid in food. The
      separation was carried out by gradient elution on an anion-exchange column using
      a conductivity detector. Earlier reversed-phase LC procedures for the
      quantitation of phytic acid usually required a prepurification step. The
      prepurification can be avoided by the separation method described in this paper.
      The method is sensitive and selective, and can be rapidly and easily performed.
      It is therefore suitable for routine determination.

PMID- 9618920
TI  - Numerical simulation of band-broadening during hydrodynamic relaxation in frit
      inlet field-flow fractionation channels.
AB  - The frit-inlet technique is a promising implementation of hydrodynamic relaxation
      of samples in field-flow fractionation (FFF). The optimization of the process is
      of great importance in order to maximize overall system efficiency. The mechanism
      of band-broadening that takes place during hydrodynamic relaxation has been
      examined using a three-dimensional simulation of the flow inside the triangular
      end-piece of the channel. This is the first time this contribution to band
      broadening has been considered and studied. Particle trajectories in the absence
      of a transverse field were numerically calculated, thereby isolating this effect
      from the familiar field-driven relaxation effect. As a first step towards an
      optimization of the system, the influence of the length of frit element was
      examined. Band-broadening was examined by determining the number of particles
      passing through the triangular end-piece as a function of transit time for a
      uniform particle distribution at the injection point. Due to the complexity of
      the flow patterns within the system, it is concluded that such numerical
      simulations are necessary for the optimization of the design and operation of
      this type of channel.

PMID- 9618921
TI  - delta 13C analyses of vegetable oil fatty acid components, determined by gas
      chromatography--combustion--isotope ratio mass spectrometry, after saponification
      or regiospecific hydrolysis.
AB  - The delta 13C values of the major fatty acids of several different commercially
      important vegetable oils were measured by gas chromatography--combustion--isotope
      ratio mass spectrometry. The delta 13C values obtained were found to fall into
      two distinct groups, representing the C3 and C4 plants classes from which the
      oils were derived. The delta 13C values of the oils were measured by continuous
      flow elemental isotope ratio mass spectrometry and were found to be similar to
      their fatty acids, with slight differences between individual fatty acids.
      Investigations were then made into the influence on the delta 13C values of fatty
      acids of the position occupied on the glycerol backbone. Pancreatic lipase was
      employed to selectively hydrolyse fatty acids from the 1- and 3-positions with
      the progress of the reaction being followed by high-temperature gas
      chromatography in order to determine the optimum incubation time. The 2
      monoacylglycerols were then isolated by thin-layer chromatography and fatty acid
      methyl esters prepared. The delta 13C values obtained indicate that fatty acids
      from any position on the glycerol backbone are isotopically identical. Thus,
      whilst quantification of fatty acid composition at the 2-position and measurement
      of delta 13C values of oils and their major fatty acids are useful criteria in
      edible oil purity assessment, measurement of delta 13C values of fatty acids from
      the 2-position does not assist with oil purity assignments.

PMID- 9618922
TI  - Capillary isotachophoresis with fiber-optic Raman spectroscopic detection.
      Performance and application to ribonucleotides.
AB  - A fiber-optic Raman probe fitted with a microscope objective was used to obtain
      on-line normal Raman spectra of adenosine 5'-monophosphate, cytidine 5'
      monophosphate, guanosine 5'-monophosphate and uridine 5'-monophosphate separated
      by capillary isotachophoresis. With multimode optical fiber, the system
      interrograted a 40-micron length of capillary. Fiber-optic coupling facilitated
      use of an unmodified spectrograph and conventional capillary mounting systems.
      Raman spectra were excited with a 2W 532 nm NdYVO4, laser as the excitation
      source, with collection of 1 spectrum per second. Even at 2.10(-5) M initial
      concentration, Raman spectra were obtained at a good signal-to-noise ratio.

PMID- 9618923
TI  - Improved capillary electrophoretic separation of glycosylated oligopeptides
      through addition of poly(vinyl alcohol), and analysis by electrospray mass
      spectrometry.
AB  - A method for the analysis of O-glycosylation of peptides has been developed,
      combining capillary electrophoretic (CE) separation and electrospray ionization
      mass spectrometry. Synthetic peptides with apomucin 'tandem repeat' sequences
      which present potential O-glycosylation sites on threonine and serine residues
      were used as model system. In vitro O-glycosylated peptide samples were obtained
      by incubation of the peptides with human gastric microsomal homogenates
      containing N-acetylgalactosamine transferase activity in the presence of uridyl
      diphosphate N-acetylgalactosamine (UDP-GalNAc). CE was carried out in the
      presence of the linear polymer poly(vinyl alcohol) in the electrophoresis
      solvent, resulting in a greatly improved separation of the up to five different
      glycoforms of peptides with lengths of 8, 16 or 23 amino acids, and the
      unglycosylated peptides. After separation and peak collection, the number of
      modifications with N-acetyl galactosamine (GalNAc) could be determined by
      electrospray ionization mass spectrometry. The glycosylation pattern was shown to
      depend on the amino acid sequence of the peptides.

PMID- 9618924
TI  - Multiresidue determination of pesticides in apples and pears by gas
      chromatography-mass spectrometry.
AB  - This paper describes a rapid, specific and sensitive multiresidue method for the
      routine analysis of several classes of pesticides used for the treatment of
      apples and pears, involving a rapid extraction procedure at pH 4.5 with a mixture
      of acetone-dichloromethane-hexane (50:20:30, v/v/v) and gas chromatography
      coupled to mass-selective detection, in order to achieve quantitative analysis
      down to their respective maximum residue limit. Extraction recoveries were
      between 55 and 98%. Limits of detection and limits of quantitation ranged
      respectively, from 0.01 to 0.05 mg/kg and from 0.02 to 0.1 mg/kg. Intra-assay
      relative standard deviation was less than 19% for all compounds. An excellent
      linearity was observed from these LOQs up to 500 mg/kg. Intermediate (inter
      assay) precision and accuracy were satisfactory. The method has been applied to
      many fruit samples intended for commercialisation.

PMID- 9618925
TI  - Menstruation: a nonadaptive consequence of uterine evolution.
AB  - Although adaptive explanations for menstruation go back at least twenty-five
      hundred years, in the last decade two new hypotheses have been advanced. The
      first suggests that menstruation evolved to cleanse the uterus of pathogens
      introduced by sperm, and the second argues that the function of endometrial
      regression (with the associated menstruation in humans) is to save energy by
      getting rid of tissue, rather than maintaining it in the absence of an available
      blastocyst. Both these suggestions may be questioned on the grounds that they do
      not take into account the physiology of the reproductive processes involved.
      Menstruation is not an independent physiological process and is unlikely to have
      been selected for independently of the evolutionary events that led to it.
      Furthermore, most primitive menstruating animals would have menstruated
      infrequently, and many may have reproduced or died without ever menstruating. In
      order to provide a context for understanding how menstruation may have come
      about, the evolution of the female vertebrate reproductive tract is briefly
      reviewed. In later stages, the coevolution of the embryo and uterus resulted in
      an intimate association between the trophoblast and the uterine blood vessels. As
      the embryo became more invasive, the uterus responded with increased cellular
      growth and differentiation of the endometrium to accommodate it. This reached its
      peak in mammals (such as rodents and humans), where the embryo passes through the
      epithelium into the endometrial stroma, which responds with differentiation of
      cells and blood vessels. Progesterone, secreted after ovulation, plays a crucial
      role in preparation for pregnancy. In addition to its well-known effects on the
      uterus, progesterone may be important in suppressing the inflammatory reaction
      that would be expected in response to the presence of a foreign body, such as an
      embryo. It is also suggested that vascular and cellular differentiation of the
      endometrial stroma has evolved by adaptation of the inflammatory (granulation
      tissue) reaction. When progesterone levels fall at the end of the cycle, there is
      tissue breakdown and bleeding. The uterus then reforms for the next ovulatory
      cycle. It is shown that the female reproductive tract has multiple functions that
      must occur in sequence. The coevolution of the embryo and maternal tract thus led
      to the close contact of two genetically different tissues, and problems such as
      the inflammatory reaction had to be overcome. Menstruation is a necessary
      consequence of these evolutionary changes, and needed no adaptive value in order
      to evolve.

PMID- 9618926
TI  - Congener specific PCB and polychlorinated camphene (toxaphene) levels in Svalbard
      ringed seals (Phoca hispida) in relation to sex, age, condition and cytochrome
      P450 enzyme activity.
AB  - Congener specific PCB and toxaphene (polychlorinated camphene, PCC) analyses were
      performed in seal blubber, collected in Svalbard, Norway. The concentration, body
      burden and metabolic index (PCB congener concentration in seal relative to their
      prey) were calculated. Multiple regression analyses were carried out to evaluate
      the influence of age, sex, blubber (as a percentage of total body weight) and
      cytochrome P450 activities on PCB and PCC levels. Levels of total PCBs found were
      five times higher than in ringed seals from the Canadian Arctic, corresponding
      with the relatively high contaminant levels in the European Arctic. The dominant
      PCB congeners (> 70% of the total PCBs measured) were 153, 138, 99, 180 and 101.
      The observed PCB and PCC accumulation patterns were very similar to patterns in
      seals from other studies, suggesting a large resemblance in contaminant
      metabolism. A decrease in the relative abundance of the lower chlorinated PCBs,
      was associated with higher concentrations of PCB 153. Since there was no
      indication for selective PCB excretion by lactating females, this suggests
      metabolism of these PCBs in ringed seals due to xenobiotic metabolising enzymes.
      The metabolic index confirmed the model of persistency of the different PCBs
      except for congener 128 and 138. These congeners, considered persistent in seals,
      could to some extent be metabolised in ringed seals. However, co-elution of PCB
      138 with PCB 163 and of PCB 128 with TOX 50 possibly has resulted in an
      underestimation of the metabolic index for these congeners. Multiple regression
      analyses revealed a significant positive effect of age and a negative effect of
      the blubber content on the PCB concentrations. Since large fluctuations of body
      lipids occur between seasons in pinnipeds, PCB measurements should account for
      the total blubber content to avoid biased results. PCBs with vicinal H-atoms in
      the o, m or the m, p positions showed in addition a relation with cytochrome P450
      enzyme activities. Surprisingly, no effect of sex on the PCB concentrations was
      observed, probably because female ringed seals, unlike other pinnipeds, continue
      feeding during lactation. This results in only small amounts of lipid and lipid
      associated contaminants being mobilised from the blubber. Consequently,
      contaminant excretion with the milk will be low. Toxaphene concentrations found
      were low compared to levels found in the Canadian Arctic. Two congeners, TOX 26
      and TOX 50 were predominant (15 and 18%, respectively of total toxaphene). There
      was no effect of sex, age, total blubber, or cytochrome P450 activities on the
      toxaphene levels. There was also no correlation between toxaphene and PCB levels,
      which may indicate differences in exposure and metabolism between these
      contaminants. Toxaphenes did not bioaccumulate to any substantial extent in
      ringed seals.

PMID- 9618928
TI  - Urine arsenic concentrations in healthy adults as indicators of environmental
      contamination: relation with some pathologies.
AB  - Arsenic concentrations were determined in 126 urine samples by hydride generation
      atomic absorption spectrometry. Samples were mineralized with nitric acid in a
      thermostated mineralization block. This technique was compared with a method that
      involves mineralization in a microwave digestion bomb. A mean recovery percentage
      of 100.80 +/- 5.57% was obtained. The relative standard deviation ranged from 1.7
      to 10.52%. It was found that subject sex and age did not affect urine As levels
      (P > 0.05). The mean urine As levels in patients with hepatic injury (4.24 +/-
      1.98 micrograms/l), diabetes (3.44 +/- 2.36 micrograms/l) and myocardial
      infarction (3.64 +/- 1.85 micrograms/l) were not statistically different (P >
      0.05) to that found in the control group (healthy subjects) (3.68 +/- 2.27
      micrograms/l). This result could be related to the fact that the regulation of As
      in the human organism is independent of these diseases. Measured As
      concentrations in the eight basic health zones of the study area were not
      statistically different (P > 0.01). This fact demonstrates the existence of a
      similarly low environmental As distribution in coastal and mountainous zones.

PMID- 9618929
TI  - Snow quality in the city of Lulea, Sweden--time-variation of lead, zinc, copper
      and phosphorus.
AB  - The quality of urban snow was studied with regard to how the concentrations of
      selected metals and phosphorus vary over time. The area studied is situated in
      northern Sweden (65 degrees 36' N; 22 degrees 13' E). Snow samples were taken at
      three different locations in the city centre, approximately every second week,
      throughout winter. This study has clearly shown the importance of local
      conditions and snow clearance operations on snow quality. The study also shows
      that it is difficult to interpret and predict the concentrations of lead, zinc,
      copper and phosphorus in the snow. However, it should be possible to predict the
      mass loads of these substances from the deposition velocities, if the snow
      handling methods and routines, as well as the local circumstances are known.

PMID- 9618930
TI  - The kinetics of bioaccumulation of zinc, copper, lead and cadmium by oysters
      (Crassostrea iredalei and C. belcheri) under tropical field conditions.
AB  - A study on the kinetics of accumulation and depuration of Zn, Cu, Pb and Cd by
      the oysters (Crassostrea iredalei and Crassostrea belcheri) cultured at two
      locations in the Merbok Estuary, Malaysia was conducted. A first-order kinetic
      model was employed to fit the experimental data in order to estimate the rate
      constants for uptake and elimination processes and to predict the
      bioconcentration factors (BCF). Among the four metals studied, only the Zn
      accumulation process could not be modelled using first-order kinetics. The
      elimination rate constants estimated from depuration data for C. iredalei are
      found to be much greater than those from accumulation data. The results suggest
      that the values of kinetic parameters and BCFs derived under conditions of both
      aqueous and dietary exposure are probably more site- than species-specific.

PMID- 9618932
TI  - L-phenylalanine effect on rat brain acetylcholinesterase and Na+,K(+)-ATPase.
AB  - The effect of different L-phenylalanine (Phe) concentrations (0.1-12.1 mM), on
      acetylcholinesterase (AChE) and Na+,K(+)-ATPase activities of brain homogenate
      and pure enzymes, was investigated at 37 degrees C. AChE and Na+,K(+)-ATPase
      activities were determined according to Ellman G. L., Courtney D., Andres V. and
      Featherstone R. M. (1961), Biochem. Pharmacol. 7, 88-95 and Bowler K. and Tirri
      R. (1974), J. Neurochem. 23, 611-613) respectively, after preincubation with Phe.
      AChE activity in brain homogenate or in pure eel E.electricus enzyme showed a
      decrease, which reached up to 18% with concentrations of 0.9-12.1 mM. Brain
      homogenate Na+,K(+)-ATPase activity showed an increase 16-65% with 0.24-0.9 mM of
      Phe, while an activity increase of 60-65% appeared with 0.9-12.1 mM of Phe. Pure
      enzyme activity (from porcine cerebral cortex) was not affected by high Phe
      concentrations, while it was increased by low concentrations. The above results
      suggest: a) A direct effect of Phe on AChE, b) A direct effect of low Phe
      concentrations and an indirect effect of high ones on Na+,K(+)-ATPase.

PMID- 9618933
TI  - Effect of aging on the activities of acetylcholinesterase, Na+,K(+)-ATPase and
      Mg(2+)-ATPase in rat pituitary and hypothalamus.
AB  - Acetylcholinesterase (AChE), Na+,K(+)-ATPase and Mg(2+)-ATPase activities were
      estimated in homogenised rat pituitary and hypothalamus of 4- and 22-month-old
      rats. AChE activity was not altered in the pituitary of aged compared to adult
      rats, while it was found decreased by about 40% in the hypothalamus. Na+,K(+)
      ATPase activity remained stable in the hypothalamus, while it was decreased by
      about 38% in the pituitary. Mg(2+)-ATPase activity remained unchanged in the
      hypothalamus, but was increased by about 83% in the pituitary. This pituitary
      Na+,K(+)-ATPase inactivation may result in pathological mood and decreased neural
      excitability and metabolic energy production in aged animals. The age-related
      alterations of AChE, Na+,K(+)-ATPase and Mg(2+)-ATPase activities may reflect
      changes in secretion and responses of some hormones of pituitary and
      hypothalamus.

PMID- 9618934
TI  - Interaction of the anticancer drug tamoxifen with the human erythrocyte membrane
      and molecular models.
AB  - Tamoxifen is a non steroidal antiestrogen drug extensively used in the prevention
      and treatment of hormone-dependent breast cancer. To evaluate its perturbing
      effect upon cell membranes it was made to interact with human erythrocytes and
      molecular models. These consisted of bilayers of dimyristoylphosphatidylcholine
      (DMPC) and of dimyristoylphosphatidylethanolamine (DMPE), representative of
      phospholipids classes located in the outer and inner leaflets of the erythrocyte
      membrane, respectively. Experiments by fluorescence spectroscopy showed that
      tamoxifen interacted with DMPC vesicles fluidizing both its polar head and acyl
      chain regions. These results were confirmed by X-ray diffraction which indicated
      that tamoxifen perturbed the same regions of the lipid. However, it did not cause
      any significant structural perturbation to DMPE bilayers. The examination by
      electron microscopy of human erythrocytes incubated with tamoxifen revealed that
      they changed their normal discoid shape to stomatocytes. According to the bilayer
      couple hypothesis, this result means that the drug is inserted in the inner
      leaflet of the erythrocyte membrane. Given the fact that tamoxifen did not
      interact with DMPE, it is concluded that it interacted with a protein located in
      the cytoplasmic moiety of the erythrocyte membrane.

PMID- 9618935
TI  - ESR study of the liposome membrane physical parameters in the heating-cooling
      cycles.
AB  - Changes of dynamic and structural parameters of egg yolk lecithin (EYL) liposome
      membranes in the heating-cooling cycles have been studied using the ESR spin
      probe method. The investigations were conducted in the range of temperatures from
      -18 degrees C to +60 degrees C. It has been found that in the range of
      temperatures -15 degrees C to +45 degrees C in both the heating and the cooling
      run the spectroscopic parameters changed practically along the same curve
      (reversible changes). However, after exceeding this range of temperatures one of
      the parameters (partition coefficient of the spin probe 2,2,6,6-
      tetramethylpiperidine -1-oxyl; TEMPO) changed along a closed curve, showing the
      phenomenon of thermal hysteresis. In the heating process the TEMPO content in
      liposome membranes was smaller than this in the cooling process. We assume that
      during the heating, the lipid molecules of the outer liposome layers dissolve in
      the aqueous medium. In the cooling process they can aggregate and form new
      liposomes, what in turn increases the surface of liposome membranes, accessible
      for the TEMPO probe (active surface).

PMID- 9618936
TI  - Radical functions in vivo: a critical review of current concepts and hypotheses.
AB  - Most of the basic knowledge about radical reactions comes from radiation chemical
      studies in vitro. In view of the rapidly increasing knowledge on radical reaction
      in vivo, it is important to reconcile the fundamental physico-chemical reaction
      characteristics of radicals with the need to explain their alleged biological
      effects. Severe problems in the understanding of their in vivo action remain
      unsolved. An example is phagocytosis, which seems to be a paradigm of a
      'deleterious' radical process. The exact mechanism is not clear; so it is an open
      question whether the intruder is eventually killed by radicals (like OH) or by
      endproducts of radical reactions (like H2O2 and/or HOCl). It is even more
      difficult to understand signalling by radicals: owing to their chemical nature
      they are 'unspecifically' reacting species--they withdraw or add electrons--and
      thus their reactions are governed by redox-properties. Since all radicals have
      different redox characteristics and different molecular shapes, the usual key-and
      keyhole picture for molecular interaction does not apply, as there, is no
      reactive site conceivable which has the property of reacting with radicals
      'specifically. Our intent in this article is: (i) to briefly review some
      fundamental characteristics of in vitro radical reactions, (ii) to extrapolate
      from this to the conditions in vivo, and (iii) to discuss current hypotheses
      concerning the redox-regulation of cellular signalling. This leads us to the
      tentative conclusion that radicals per se must be tolerated by the cell and do
      not threaten its life, if they stay below a certain concentration limit. The main
      biological implication of radical-reactions seems to be that the cell derives
      signals from the balance of oxidative versus reductive processes and that
      radicals may interact with pathways of intra- and intercellular communication.

PMID- 9618937
TI  - Protection against peroxynitrite by selenoproteins.
AB  - Cellular defense against excessive peroxynitrite generation is required to
      protect against DNA strand-breaks and mutations and against interference with
      protein tyrosine-based signaling and other protein functions due to formation of
      3-nitrotyrosine. We recently demonstrated a role of selenium-containing enzymes
      catalyzing peroxynitrite reduction. Glutathione peroxidase (GPx) protected
      against the oxidation of dihydrorhodamine 123 (DHR) by peroxynitrite more
      effectively than ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one), a
      selenoorganic compound exhibiting a high second-order rate constant for the
      reaction with peroxynitrite, 2 x 10(6) M-1s-1. The maintenance of protection by
      GPx against peroxynitrite requires GSH as reductant. Similarly, selenomethionine
      but not selenomethionine oxide exhibited inhibition of rhodamine 123 formation
      from DHR caused by peroxynitrite. In steady-state experiments, in which
      peroxynitrite was infused to maintain a 0.2 microM concentration, GPx in the
      presence of GSH, but neither GPx nor GSH alone, effectively inhibited the
      hydroxylation of benzoate by peroxynitrite. Under these steady-state conditions
      peroxynitrite did not cause loss of 'classical' GPx activity. GPx, like
      selenomethionine, protected against protein 3-nitrotyrosine formation in human
      fibroblast lysates, shown in Western blots. The formation of nitrite rather than
      nitrate from peroxynitrite was enhanced by GPx, ebselen or selenomethionine. The
      selenoxides can be effectively reduced by glutathione, establishing a biological
      line of defense against peroxynitrite. The novel function of GPx as a
      peroxynitrite reductase may extend to other selenoproteins containing
      selenocysteine or selenomethionine. Recent work on organotellurium compounds
      revealed peroxynitrite reductase activity as well. Inhibition of dihydrorhodamine
      123 oxidation correlated well with the GPx-like activity of a variety of diaryl
      tellurides.

PMID- 9618938
TI  - Evaluation of the antioxidant capacity of ubiquinol and dihydrolipoic acid.
AB  - Ubiquinone and alpha-lipoic acid are natural constituents which are involved in
      mitochondrial energy metabolism. Their bioenergetic activities require redox
      cycling. In the case of alpha-lipoic acid redox-cycling leads to dihydrolipoic
      acid which occurs in multienzyme complexes involved in the citric acid cycle
      while UQ recycles through semi- and divalently reduced ubiquinones in the
      respiratory chain. We have proved the validity of the concept about the
      antioxidant function of these natural compounds in their reduced form. Ubiquinol
      was found to interfere with lipid peroxidation of liposomal membranes being
      itself degradated by two consecutive oxidation steps. Dihydrolipoic acid was
      found to totally recycle ubiquinone to the antioxidant active divalently reduced
      form. In contrast to the antioxidative derived reaction products of ubiquinols
      which in turn promoted lipid peroxidation, the antioxidant derived reaction
      product of dihydrolipoic acid was the unreactive two electron oxidation product
      alpha-lipoic acid. Our experiments demonstrate the existence of an dihydrolipoic
      acid driven recycling of UQ to the antioxidative-active UQH2. The efficiency of
      the antioxidative capacity of the latter was found to be diminished through
      prooxidant activities of the antioxidant-derived metabolites.

PMID- 9618939
TI  - Superoxide release in human fibroblasts upon treatment with culture supernatants
      of the arthritogenic bacteria Erysipelothrix rhusiopathiae and Mycoplasma
      arthritidis.
AB  - Culture supernatants of the arthritogenic bacteria Mycoplasma pneumonia,
      Mycoplasma arthritidis, Borrelia burgdorferi and Erysipelothrix rhusiopathiae
      stimulated primary cultures of human fibroblasts to release reactive oxygen
      species into the environment, whereas cell walls and membranes of these bacteria
      had no effects. Lipopolysaccharides of various gram-negative bacteria and lipid
      A, the lipid moiety of endotoxines, also failed to stimulate the release of
      reactive oxygen species by fibroblasts. The stimulatory fractions of the culture
      supernatants of Mycoplasma arthritidis and Erysipelothrix rhusiopathiae exhibited
      a molecular weight of about 9.5 kDa. After an induction period of 5 min the
      presence of the stimulant was not necessary any more. The primary radical
      released by the fibroblasts was the superoxide anion O2-. Radical formation took
      place continuously over some hours. Additionally, low-level chemiluminescence of
      fibroblasts was increased upon stimulation with culture supernatants of
      Mycoplasma arthritidis and Erysipelothrix rhusiopathiae. No irreversible injury
      of the fibroblast was caused upon stimulation and the cells exhibited normal
      proliferation pattern after replacing them to the culture medium.

PMID- 9618940
TI  - Sulfite induces release of lipid mediators by alveolar macrophages.
AB  - Air pollutants are supposed to modulate physiological responses of alveolar
      macrophages (AM). This study was addressed to the question whether at neutral pH
      sulfur(IV) species in comparison to sulfur(VI) species cause AM to release
      proinflammatory mediators and which pathways are involved in their generation.
      Supernatants obtained from canine AM treated with sulfite (0.1 mM to 2 mM)
      enhanced the respiratory burst of canine neutrophils, measured by lucigenin
      dependent chemiluminescence, whereas supernatants derived from AM treated with
      sulfite (1 mM) did not. The neutrophil-stimulating activity released by sulfite
      treated AM consisted of platelet-activating factor (PAF) and leukotriene B4
      (LTB4) as shown by desensitization of the corresponding receptors. Inhibitors of
      phospholipase A2 substantially suppressed release of neutrophil-stimulating
      activity by sulfite-treated AM. Inhibition of 5-lipoxygenase in sulfite-treated
      AM also reduced neutrophil-stimulating activity, while inhibition of
      cyclooxygenase had no effect. In conclusion, sulfite induces AM to release lipid
      mediators via phospholipase A2- and 5-lipoxygenase-dependent pathways. These
      mediators activate neutrophils via the receptors for PAF and LTB4.

PMID- 9618941
TI  - Protective effect of vitamin E in a rat model of focal cerebral ischemia.
AB  - Under certain pathological conditions such as cerebral ischemia and reperfusion
      the occurrence of free radicals is remarkably increased. However, only very
      little information is available on their quantitative relevance for the
      pathophysiology and final outcome of diseases. The aim of the present study was
      to evaluate the contribution of oxygen radicals in the pathogenesis of a stroke.
      For this purpose a rat model for stroke was used. Two of three vitamin E
      deficient groups were repleted with different dosages of DL-alpha
      tocopherylacetate. No signs of vitamin E deficiency could be observed. However,
      the weight gain during repletion was increased in the vitamin E repleted groups.
      Brain infarction was created by occlusion of the right middle cerebral artery
      (MCAO) for two hours. After 24 hours the measurements of infarct volumes were
      taken. The infarct volume of the group with the highest repletion dosage was
      significantly reduced by 81%. This was also expressed in a higher rate of gait
      disturbances after MCAO of the deficient animals. The control of vitamin E status
      exhibited a similar repletion-dependent level in plasma and brain. These results
      strongly support the hypothesis that the generation of oxygen radicals occurring
      during reperfusion is an important aspect of the pathophysiological mechanism in
      brain infarction.

PMID- 9618942
TI  - The exogenous NADH dehydrogenase of heart mitochondria is the key enzyme
      responsible for selective cardiotoxicity of anthracyclines.
AB  - The molecular mechanism of the anthracycline-dependent development of
      cardiotoxicity is still far from being clear. However, it is generally accepted,
      that mitochondria play a significant role in triggering this organ specific
      injury. The results presented in this study demonstrate that, in contrast to
      liver mitochondria, isolated heart mitochondria shuttle single electrons to
      adriamycin, giving rise to oxygen radical formation via autoxidation of
      adriamycin semiquinones. This one electron reduction of anthracyclines is
      catalyzed by the exogenous NADH dehydrogenase associated with complex I of heart
      mitochondria, an enzyme which is lacking in liver mitochondria. Upon addition of
      NADH heart mitochondria generate significant amounts of adriamycin semiquinones
      while liver mitochondria were ineffective. Adriamycin semiquinones undergo both
      autoxidation leading to superoxide radical release and complex reactions under
      formation of adriamycin aglycone. Due to the high lipophilicity adriamycin
      aglycones accumulate in the inner mitochondrial membrane where they interfere
      with electron carriers of the respiratory chain. Adriamycin aglycone semiquinones
      emerging from an interaction with complex I were found to trigger homolytic
      cleavage of H2O2 which results in the formation of hydroxyl radicals. As
      demonstrated in this study the activation of adriamycin by the exogenous NADH
      dehydrogenase of cardiac mitochondria initiates a cascade of reaction steps
      leading to the establishment of oxidative stress. Our experiments suggest the
      exogenous NADH dehydrogenase of heart mitochondria to play a key role in the
      cardiotoxicity of adriamycin. This organ-specific enzyme initiates a sequence of
      one electron transfer reactions ending up in the establishment of oxidative
      stress.

PMID- 9618943
TI  - In vitro influence of phenylalanine on acetylcholinesterase activity and DNA.
AB  - Acetylcholinesterase (AChE) is a significant component of the membrane
      contributing to the permeability changes during synaptic transmission and
      conduction. Phenylketonuria is a group of metabolic disorders in which
      phenylalanine (Phe) is highly elevated in blood (up to 0.1 M) resulting in mental
      retardation etc. AChE activity was measured spectrophotometrically after
      incubation with various Phe concentrations. Phe interaction with DNA was
      evaluated with an established HPLC method. Phe was found to inhibit AChE almost
      40%, at a concentration of 5 mM, whereas a 62.5% DNA peak exclusion (molecular
      interaction) was observed when Phe was incubated with DNA at a concentration of 3
      mM. In addition the ratio of DNA: Phe determined the potency of the observed
      molecular effect.

PMID- 9618944
TI  - Development and characterization of new immortalized human breast cell lines
AB  - New human breast cell lines were developed from metastatic breast cancer tissues
      and normal breast tissues. Primary cultures were initiated from cellular
      outgrowths of explanted tissues or from mechanically isolated cells in two serum
      free media. Cell cultures derived from both cancer and normal tissues were
      immortalized with pRSV-T plasmid to generate permanent breast cell lines that
      exhibited an epithelial morphology. Cell lines generated in this study were
      characterized with respect to morphology, growth rate, karyotype, presence of
      specific genes, and the expression of epithelial and breast markers. The cell
      lines expressed the epithelial cell markers, cytokeratins 8 and 18, and retained
      the capacity to produce human milk fat globulin. They also express the BRCA-1,
      erbB2, and EGF receptor genes and possess the H-ras, K-ras, and p53 genes.
      Preliminary data showed that one of the new cancer cell lines was highly
      sensitive to the cytotoxic action of taxol. It is envisioned that the new breast
      cell lines will be useful as targets for identification of therapeutic agents
      against breast cancer and as models for carcinogenesis studies.

PMID- 9618945
TI  - [The effect of the duration of the dry period and of the use of antibiotics on
      the development of congenital infection in the newborn infant during premature
      rupture of the fetal membranes].
AB  - A retrospective study including 41 patients with preterm premature rupture of the
      membranes (PPROM) was carried out to investigate the influence of some factors
      (interval between PPROM and delivery, antibiotic administration) on the
      development of congenital infections of the newborn. When the PPROM--delivery
      interval exceeds 168 hours the infection rate is very high. The latter is lower
      when cephalosporin antibiotics instead of ampicillin are administered to the
      pregnant patient with PPROM.

PMID- 9618946
TI  - [Twin pregnancy. Its incidence].
AB  - The authors evaluate changes in the incidence and proportion of the life births
      by plurality in Mothernal Hospital in Sofia between 1991-1995 and compare it with
      the incidence of multiple births in other countries in the world. The influence
      of some factors on the incidence of multiple pregnancy are discussed.

PMID- 9618947
TI  - [The lead level in the blood of pregnant women from the city of Sofia].
AB  - The study was aimed at establishing the relation between blood lead, nutrient
      intake and smoking habits of pregnant and nonpregnant women in Sofia. Forty four
      pregnant in the last trimester of pregnancy and 14 nonpregnant women were
      examined. There are no differences between the mean blood lead level of the
      groups. 22.72% of the pregnant and 37.7% of the nonpregnant women studied had
      blood lead above the accepted tolerable value of 0.48 mumol/l. It was established
      low intake of calcium, zinc and iron, minerals that contribute to lead
      bioavailability. A positive correlation between the number of cigarettes smoked
      and blood lead concentration was established. Based on this study it can be
      concluded that non-professional external exposure of lead in Sofia is
      significant. Smoking is eventually one contributing factor that can be excluded
      to reduce lead exposure.

PMID- 9618948
TI  - [The plasma concentrations of thiocyanates, estradiol (E2), follicle-stimulating
      hormone (FSH) and prolactin (Prl) in women smokers].
AB  - By the help of biochemical methods we examined the plasma concentrations of
      thiocyanate during the placental period of the delivery both in mothers and the
      umbilical vein of the newborn babies. Using radiological methods we
      simultaneously examined the levels of E2, FSH, and Prl. The results suggest high
      correlation, between the plasma levels of thiocyanate both and newborn babies. We
      observed a low positive correlation, conserving the concentration of thiocyanates
      in mothers and E2 and Prl. There was a negative correlation, concerning the
      plasma FSH. We also observed similar interrelations in the blood examinations of
      the umbilical vein of the newborns. To define the level of intoxication of women
      smokers during gestation it is recommended to define plasma concentration of
      thiocyanates which influence specifically the production of E2, FSH, and Prl.

PMID- 9618949
TI  - [The copper concentration in the maternal serum in missed abortion].
AB  - Two groups of women with missed abortion examined in different periods of time
      were included in the study--the first group of 43 patients was examined in 1989
      1990 and the second group of 24 in 1994. The control group consist of 73 women in
      the first trimester of normal pregnancy and 75 nonpregnant women. The serum
      copper concentration of the first group with missed abortion (19.47 +/- 4.62
      mumol/l) was significantly (p < 0.001) lower than those of control group with
      normal pregnancy (23.40 +/- 5.10 mumol/l). The serum concentration of the second
      group with missed abortion was even lower--17.82 +/- 2.95 mumol/l. The serum
      copper level was measured directly with flame atomic absorption spectrometry. The
      histology reveals dystrophic and necrotic changes and also inflammatory changes
      with edema of chorion villi without enhanced collagenisation. We discuss the
      possible mechanisms of the observed changes.

PMID- 9618950
TI  - [The amniotic fluid volume in uncomplicated singleton pregnancies: the ultrasonic
      study technics].
AB  - In 750 uncomplicated singleton pregnancies, 1765 examinations have performed to
      establish the normograms for 4 Ultrasound techniques of measurement of amniotic
      fluid volume (AFV). The 90% and 95% and 98% confidence intervals for each method
      across gestation (16-43 weeks) were calculated from polynomial regression
      equation for 50th percentile from logarithmic transformed data, and antilog
      values were plotted in graphical representation for modified amniotic fluid Index
      (MAFI). The variations of the mean values of data between weeks were
      statistically significant (p < 0.00001). Normograms show the progressive increase
      of AFV up to 27-29 weeks (27-32 weeks plateau), then declined to term. In
      postdate period the decrease of AFV was 7%-10% weekly for MAFI. In term
      gestation, the mean AFV of 5th and 95th percentile that defines the lower and
      upper limits were 6.7 & 21.3 cm for MAFI, 6.2 & 19.9 cm for AFI (amniotic fluid
      index), and for maximum vertical single pocket (MVP)--2.5 & 7.4 cm and for two
      diameter pocket (TDP)--10.4 & 51.0 c2.

PMID- 9618951
TI  - [Perinatal problems and the prevention of premature labor].
AB  - An analysis of the principal indices, associated with the perinatal mortality
      rate of premature infants and the level of prematurity during the last 3 years,
      compared with those of 1989 and the similar indices in the developed countries of
      Europe and North America is presented. The main trends in prenatal and intranatal
      prevention of the premature delivery and the complications associated with it are
      discussed. The most common neonatal morbidity of the premature infants with very
      low birthweight and the contemporary possibilities of prevention are described.

PMID- 9618952
TI  - [The use of clofelin for the treatment of arterial hypertension and for the
      anesthesia of labor].
AB  - Fourteen women in labor with pregnancy of 39.1 +/- 1.1 gestational weeks and
      arterial hypertension (BSP of 183.4 +/- 12.4 and BDP of 90.6 +/- 14.3 mm Hg) were
      given chlopheline with a rate of infusion 0.0005, 0.001 mg/kg/hr for 120 min.
      Decrease of arterial pressure began at minute 15.7 +/- 0.3 after starting
      perfusion, and the hypotensive effect lasted for 300 minutes. At minute 360, a
      new dose of chlopheline was needed. Against the background of arterial
      hypertension, a decrease of BSP, BDP and P was observed, and the central
      hemodynamics remained unchanged within statistically reliable range. The changes
      observed in the hemodynamics did not affect labor activity and the fetus. The
      analgesic effect of chlopheline was favorable. Perfusion of chlopheline at a rate
      of infusion 0.0005, 0.001 mg/kg/hr is a choice to provide a bulk of positive
      hypotensive and analgesic affect on the woman in labor.

PMID- 9618953
TI  - [The structure of the morbidity in very low birth weight premature infants].
AB  - It is a retrospective study, enrolling 255 liveborn premature infants, born up to
      32 gestational weeks and below 1500 grams, who were admitted to the Intensive
      Care Unit of our hospital from 1993 to 1996. The aim of the study is to establish
      the most common disorders inside this group of high risk newborns. Among
      survivors is obvious the prevalence of pulmonary pathology (81.8%) and
      intraventricular hemorrhage (61.9%). The incidence of chronic lung disease is
      15.4% being due to prematurity and intensive respiratory resuscitation. Inside
      this group of premature babies, the fact is observed that asphyxia intra partum
      does not play the leading role for the outcome, because many factors influence
      mortality rate there. The higher incidence of survival of babies below 1000 g is
      related to development of modern intensive care.

PMID- 9618954
TI  - [The mortality of very low birth weight infants at birth].
AB  - The aim of our study is to obtain descriptive data on neonatal mortality in VLBW
      infants. A retrospective study of 573 VLBW infants who had been treated in the
      INCU of the Neonatal Clinic was performed. 173 from them died (30.2%). Three
      groups were stratified according to gestational age: 1st group under 25 g.w.--26
      infants, 2nd group 26-28 g.w.--80 infants, 3rd group 29-32 g.w.--67 infants.
      Among the children from the 1st and 2nd group IV H prevail--81% and respectively
      76%. RDS is the most prevalent cause of death in the 3rd group. Infection
      diseases are on the third place in all three groups.

PMID- 9618955
TI  - [The incidence and structure of the congenital malformations in very low birth
      weight liveborn infants over 1991-1995 at the Maternity Home of the State
      University Hospital, Sofia].
AB  - This retrospective study, performed in University Maternity Hospital "Maichin
      dom"--Sofia for the period 1991-1995, shows that the frequency of congenital
      malformations among the live born VLBW neonates is approximately 6 times higher
      than those among newborns, weighing above 1500 g. Central nervous system
      anomalies occur the first place of the structure of congenital malformations in
      the first group, followed by anomalies of the cardio-vascular system and
      polymalformative syndromes. Great malformations are the main reason for dying in
      the neonatal period in newborns, weighing above 1500 g, while in VLBW infants
      they come on third place after perinatal asphyxia and intraventricular
      hemorrhages.

PMID- 9618956
TI  - [Unsuccessful contraception among patients seeking abortion on demand].
AB  - We have conducted a prospective study aimed to analyse contraceptive use among
      women seeking for legal abortion in the State University Hospital "Maichin dom"-
      Sofia. Our date demonstrate that the patients were well informed about the
      existing contraceptive methods. On the contrary the percentage of women-using
      contraception and especially those, using highly effective ones is relatively
      low. The patients claim the possible side effects of the high effective
      contraception as a reason against use.

PMID- 9618957
TI  - [Laparoscopic uterosacral neural ablation].

PMID- 9618958
TI  - [The sociomedical and risk-insuring protection of women depending on their
      reproductive function].
AB  - The role and importance of accomplished fertility compared to the total number of
      pregnancies is discussed from the point of view of working activities, medico
      social insurance and amount of risk insurance indemnities of women during
      different phases of the individual reproductive cycle for the period 1985-1995 in
      Bulgaria. It is pointed out that the continuing unfavourable demographic
      tendencies are directly linked with the level of the reproductive function of
      women. Their individual behaviour in the accomplishment of that function is
      motivated mainly by changes of economic factors, optimal social insurance
      indemnities during different phases of the cycle, success in the control of
      pregnancy complications and especially increasing emotional acceptance of
      abortions, which sharply exceed births.

PMID- 9618959
TI  - [Congenital syphilis].

PMID- 9618960
TI  - [Epithelial changes in the cervix uteri in pregnant women and in cervical
      oncogenesis].
AB  - The changes in the growth and differentiation of the cervical epithelium induced
      during pregnancy by hormonal influence and anatomical alterations are discussed
      regarding their magnitude on cervical oncogenesis. Question about the necessity
      of the self-sufficient centralized reporting of the pregnant women with precancer
      and cancer lesions is put on.

PMID- 9618961
TI  - [Endometrial hyperplasia and carcinoma in situ].
AB  - Endometrial hyperplasias--both simple and adenomatous are presented, as well as
      the differences between them and the endometrial carcinoma. The concept of
      endometrial carcinoma in situ (ESIS) and the criteria for invasiveness by the
      malignancies of the uterine corpus are discussed. Illustrations for various cases
      with ESIS are provided and the clinical behaviour by ESIS is discussed.

PMID- 9618962
TI  - [Acute gynecological abdomen caused by the rupture of a necrotized myomatous
      node].

PMID- 9618963
TI  - [Massive ovarian edema--a case report].
AB  - A case with massive ovarian oedema, which is a rare pseudotumorous condition in
      young women, is described. The conceptions about the etiology and pathogenesis
      are considered as well as the morphological changes (with the corresponding
      clinical symptoms) which could be found in the affected ovary. Attention is drawn
      to the differential diagnostical difficulties and to the possibilities of
      semiconservative treatment of this rare clinicomorphological entity.

PMID- 9618964
TI  - [A rare case of an adenomatoid mesothelioma of the fallopian tube combined with
      ovarian stromal hyperplasia and hyperthecosis, endometrial adenocarcinoma and
      endometriosis interna].
AB  - Adenomatoid mesothelioma is a rare benign tumor, most commonly located in the
      uterine corpus and fallopian tubes in the women during the reproductive years. It
      usually occurs occasionally and there are no specific symptoms. A case is
      presented of an adenomatoid tumor of the fallopian tube, associated with many
      other pathological findings of the genital tract. It is important to recognize
      the pseudoglandular pattern of this rare kind of benign tumor to avoid a mistaken
      diagnosis of adenocarcinoma or metastasis.

PMID- 9618965
TI  - [The use of recombinant erythropoietin to correct a postoperative anemic syndrome
      after cesarean section--a case from clinical practice].

PMID- 9618969
TI  - Synthesis and biological evaluation of certain new thiazolopyrimidines.
AB  - A series of 5-methyl-3-phenyl thiazolo[5,4-e][1,2,4]triazolo[1,5-c] pyrimidin-2
      thiones and 5-methyl-3-phenyl thiazolo[5,4-e]pyrimidino[3,4-b][1,2,4]triazin-2
      thiones were prepared as potential antimicrobial and antitumor agents. Some of
      the tested compounds showed promising activity. The detailed synthesis,
      spectroscopic and biological data are reported.

PMID- 9618966
TI  - [The use of the antibiotic cefoxitin (Mefoxin) in gynecological practice].
AB  - The aim of this presentation is to study the advantages and disadvantages of
      perioperative prophylaxis with the antibiotic Mefoxin against the classical
      postoperative antibiotic prophylaxis with penicillin and gentamicine, as well as
      to analyse the place of this antibiotic in modern treatment of different forms of
      pelvic inflammatory disease. The authors conclude that the qualities of Mefoxin
      (high resistant wide spectrum antibiotic, covering aerobes and anaerobes), make
      it an ideal antibiotic for perioperative prophylaxis in gynaecologic and
      oncologic surgery; the clinical effectiveness of Mefoxin in the treatment of
      inflammatory diseases of the female pelvis precludes the need for a combined
      parenteral antibiotic therapy.

PMID- 9618970
TI  - Joint fractures of the proximal end of the femur during childhood.
AB  - A total of 18 joint fractures of the proximal end of the femur in patients aged
      under 16 years (all treated non-surgically) are reported. Complete clinical
      radiographic documentation was available for all 16 of them, with a minimum
      follow-up of 2 years. Results were evaluated based on the Ratliff criteria. The
      incidence of complications (in particular, avascular necrosis) was related to the
      type of fracture (Delbet classification) and to the degree of shifting of the
      segments (Boitzy).

PMID- 9618971
TI  - Retrograde intramedullary osteosynthesis in the surgical treatment of fractures
      of the radial capitellum during childhood.
AB  - The authors report 12 cases of fracture of the radial capitellum occurring during
      childhood, treated by retrograde intramedullary osteosynthesis. Preoperative
      assessment involved the four-stage "prognostic-therapeutic" radiographic method
      proposed by Metaizeau. The results were extremely encouraging, 92% excellent and
      good, particularly when there were no (except in one case) severe complications
      (necrosis of the head, pseudarthrosis, poor consolidation, synostosis) typical of
      these traumatic lesions. At the same time clinical data observed, in agreement
      with what is reported in the literature, confirmed that the principal prognostic
      factors are represented by the amount of traumatic lesion, and above all by
      epiphyseal dislocation, the quality of reduction obtained, and the age of the
      patient.

PMID- 9618972
TI  - Arthroscopic surgery of the discoid meniscus during childhood.
AB  - A total of 43 lateral discoid menisci in 38 patients submitted to arthroscopy
      between 1990 and 1995 is discussed. Age ranged from 2 to 14 years. Morphological
      changes of the lateral meniscus were classified according to Watanabe criteria.
      The features of preoperative symptoms were related to the type of meniscal lesion
      and to the age of the patient, and the results evaluated according to the Ikeuchi
      scale.

PMID- 9618973
TI  - Reconstruction techniques in the treatment of vertebral neoplasms.
AB  - The authors present a new system for the topographical description of vertebral
      neoplasms. The general criteria of reconstruction after curettage or vertebral
      resection are evaluated. The literature is reviewed in terms of the use of
      prostheses, bone grafts, cement and stabilization systems in the treatment of
      tumors of the spine. Indications for the different methods are discussed.

PMID- 9618974
TI  - Neurologic deficit after resection of the sacrum.
AB  - The authors describe neurologic deficit (sensory, motor, and sphincteral)
      resulting from sacrifice of the sacral nerve roots removed during resection of
      the sacrum. The anatomical and functional bases of sphincteral continence and the
      amount of neurologic deficit are discussed based on level of sacral resection. A
      large review of the literature on the subject is reported and discussed. The
      authors emphasize how the neurophysiological bases of sphincteral continence
      (rectum and bladder) and of sexual ability are still not well known, and how the
      literature reveals disagreement on the subject. A score system is proposed to
      evaluate neurologic deficit. The clinical model of neurologic deficit caused by
      resection of the sacrum may be extended to an evaluation of post-traumatic
      deficit.

PMID- 9618975
TI  - The treatment of giant cell tumors by curettage and filling with acrylic cement.
      Long-term functional results.
AB  - Curettage and filling with acrylic cement in the treatment of para-articular
      giant cell tumor (GCT) has multiple advantages as compared to other methods;
      nonetheless, the possibility of progression in arthrosis is still a drawback. The
      literature does not report long-term functional results when this method was
      used. Four cases are presented with a mean long-term follow-up of 13.5 years
      (minimum 11, maximum 18). Clinical results, evaluated by the Enneking system
      (18), were excellent, and there were no radiological modifications, so that we
      believe that this is the method to choose for Campanacci stage I and II GCT (1),
      and in some stage III cases, as joint function is not compromised in time.

PMID- 9618976
TI  - Clinical study of the effect of hydroxyapatite on osteointegration by total hip
      replacement.
AB  - From 5.1989 to 12.1992, the Walter-Motorlet cementless hip endoprosthesis
      provided with "Arbond" hydroxyapatite coating was clinically tested. This femoral
      component was applied to 34 patients, among those 26 women and 8 men having the
      average age of 42 years (range 24-82 years). We compared the results with a
      control group of patients constituted of 20 men and 49 women on average 48.3
      years of age, in which the same type of endoprosthesis was used, but without
      hydroxyapatite coating. Both groups were evaluated by the same surgeons according
      to the usual international standards (ALLOPRO CHART). The substantially higher
      quality of the osteointegration of the hydroxypatite implants especially where
      primary osseous fixation is not quite stable and thus not perfect is undoubtedly
      evident from this study.

PMID- 9618977
TI  - Metal-UHWMPE (Ultra High Molecular Weight Polyethylene) wear: experimental
      testing.
AB  - Testing conducted on a hip joint simulator verified the Charnley hypothesis that
      the diameter of the prosthetic head is proportional to wear. The study was
      conducted by pairing heads in Ortinox TM with acetabular cups in polyethylene at
      high molecular weight (UHMWPE). A comparison between the different sizes of the
      heads (26 and 30 mm in diameter) showed a different trend in the wear rate; in
      particular, the head with a smaller diameter behaves better tribologically than
      the head with a larger diameter.

PMID- 9618978
TI  - Chondromalacia of the patella. Natural progression.
AB  - A total of 42 cases of patellar pain in subjects aged an average of 17.2 years
      submitted to arthroscopy are analyzed. Femoropatellar balance, where indicated,
      led to resolution of disorders with full resumption of sports activity. In the
      remaining cases chondromalacia showed the features of an affection with a
      spontaneously favorable course, confirming the common orientation towards
      conservative treatment. Arthroscopy is effective for a correct classification of
      cartilaginous lesions, and it is a good instrument to use when attempting to
      achieve recovery of patellofemoral joint when disorders are caused by a lack of
      equilibrium.

PMID- 9618979
TI  - Reimplantation of the upper limb after tear lesion: long-term results.
AB  - Reimplantation revascularization of the upper limb proximal to the elbow
      represents an absolute indication in specific conditions. In the young subject,
      in good general conditions with a clean amputation (guillotine-like caused by a
      circular saw), the limb preserved in ideal conditions, indications for
      reimplantation are supported by the expectations of good functional recovery.
      When amputation is due to avulsion tear the possibility of anatomical and
      functional success is influenced by the complexity of vascular and nervous
      lesions. Thus, indications for reimplantation must be made by carefully
      evaluating each individual case.

PMID- 9618980
TI  - Tubercular osteitis of the spine of the scapula.
AB  - At present the incidence of osteoarticular tuberculosis is increasing in the
      western world. The authors describe a case of tubercular osteitis of the scapula.
      Surgical treatment in association with antitubercular therapy obtained excellent
      results.

PMID- 9618981
TI  - Transitory osteonecrosis of the head of humerus after fracture of the clavicle.
AB  - The authors present a rare case of transitory osteonecrosis of the humeral head
      with anterior instability of the glenohumeral joint, which occurred in a young
      male aged 19 years, three months after fracturing his clavicle in a fall. Core
      decompression of the humeral epiphysis and anterior capsulomioplasty according to
      Symeonides was performed. Five months after surgery the patient was clinically
      cured. After having excluded the possibility of metabolic imbalance in the
      patient, we presumed a direct relationship between the trauma and degenerative
      pathology affecting the humeral epiphysis.

PMID- 9618982
TI  - An atypical case of osteoid osteoma.

PMID- 9618983
TI  - [Necrotizing vasculitis of the cerebral and spinal leptomeninges in a Bernese
      mountain dog].
AB  - A case of necrotizing vasculitis involving the central nervous system in a seven
      month old Bernese mountain dog is reported. The clinical signs include apathy,
      fever and increased head and cervical pain. The cerebrospinal fluid was unusual
      viscous and bloody. In the EEG high activity and spikes were found. A
      hydrocephalus internus was confirmed by CT scan. On histopathological examination
      a necrotizing vasculitis on the medulla oblongata and spinal cord leptomeninges
      with perivascular granulomatous inflammation were detected. The neuropathological
      lesions are consistent with those reported for the rare disease of necrotizing
      vasculitis in the central nervous system of Bernese mountain dogs, beagles and
      boxers. The cause is unknown.

PMID- 9618984
TI  - Pathological and in situ hybridisation findings in calves experimentally infected
      with bovine adenovirus type 4.
AB  - Three colostrum deprived calves were inoculated intravenously with a strain of
      bovine adenovirus type 4 (BAV-4) isolated from a calf with acute fibrinous
      enteritis. The calves were monitored clinically and submitted to post mortem
      examination at 5, 6 and 10 days post inoculation (p. i.) respectively. The 3
      animals showed raise in temperature and diarrhoea. Acute enteritis was observed
      in calves submitted to post mortem examination at 5 and 6 days p. i. In these
      animals viral DNA was specifically detected on histological sections by an in
      situ hybridization (ISH) technique; BAV-4 was isolated from most of the organs
      and numerous adenovirus-positive endothelial cells were present in the
      gastrointestinal tract, mesenteric lymph nodes and liver. In the calf examined 10
      days p. i. no lesions were observed and rare ISH positive cells were detected.
      These results indicate that in experimental conditions our strain of BAV-4 is
      capable to induce clinical signs and lesions similar to those reported in field
      cases.

PMID- 9618985
TI  - [Pestivirus as causative agent of abortion and perinatal mortality in cattle and
      sheep in Switzerland].
AB  - The causal involvement of bovine viral diarrhoea virus (BVDV) and border disease
      virus (BDV) infection in bovine and ovine abortion and perinatal mortality remain
      unclear. From 1992 until 1994, 213 bovine and 31 ovine foetuses as well as 36
      calves and 25 lambs which had died perinatally were investigated. Tissue samples
      were tested for the presence of pestiviruses and serum or fluid from the body
      cavities were analysed for the presence of pestivirus antibodies. Detection of
      pestiviruses was performed by (i) cell culture isolation, (ii) antigen ELISA and
      (iii) immunohistochemical staining for viral antigen. For antibody-testing an
      indirect ELISA was used. In nine bovine foetuses and in two calves BVDV was
      isolated. Pestiviruses, most likely BDV were detected in one ovine foetus and
      three lambs. In 6% of the bovine and 11% of the ovine foetuses anti-pestivirus
      antibodies were detected. However, clinical features and history of bovine cases
      did not show a correlation with the diagnostic results, In contrast, the presence
      of central nervous system signs in neonatal lambs and the detection of BDV was
      correlated.

PMID- 9618986
TI  - [Lysozyme activity in the milk of sucking mares during lactation].
AB  - It was the aim of this project to investigate the changes of the lysozyme
      activity in the milk of mares during the lactation period. Further on the
      influence of race, date of conception and foaling, age and number of lactations
      on the lysozyme activities in milk was analysed. Milk samples were collected from
      44 mares (trotters, warmblood, quarter horses) from eight farms between the 1st
      and 90th day p. p. The activity of the lysozyme was measured by a turbidometric
      method. Summarizing the following results are obtained: Lysozyme activities in
      mare milk of the 1st and 3rd day p. p. were higher than in mature milk. On
      average the highest lysozyme activity (Xa = 113.600 +/- 25.171 U/ml) was measured
      on the 3rd day p. p. Until the 9th day p. p. the activity decreased about 25%,
      afterwards there was only a slight decrease. The lowest activity (Xa = 57.509 +/-
      14.606 U/ml) was measured at the 83rd day p. p. The influence of race and
      conception time proved to be statistically significant resp. highly significant.

PMID- 9618987
TI  - [Immunoglobulin transfer in the viable, newborn calf].
AB  - Parturitions of 26 dairy-cows were observed and the viability of the newborn
      calves assessed. Immediately after birth as well as after the first and forth
      colostrum intake a blood probe was taken from the neonates and investigated for
      the following parameters: blood gas, blood picture, total-IG, concentrations of
      IGG1, IGM and IGE, total proteins and albumin. Before each feeding a colostrum
      sample was assayed for the same parameters with the exception of blood gas, blood
      picture and albumin. A transferindex (KLOBASA et al., 1994) was calculated to
      investigate the absorption of TP, IG, IGG1, IGM and IGE. In some of the blood
      samples there was no IGE detectable, even after colostrum intake. High individual
      differences were striking and blood concentrations were not related to the milk
      contents or the time until first feeding. The total proteins were strongly
      correlated to the serum concentrations of IGG1, but only in samples taken after
      first colostrum feeding. Vital calves showed the following tendency: colostrum
      intake of less than 1 l within the first 15 hours after birth and/or colostrum
      intake with TP-concentrations of 80 I.U./l was partly compensated by increased
      absorption of TP. 24 hours after birth serum-immunoglobulinconcentrations were 6
      12 mg/ml; weight gain was normal and no calf became ill. In 60% of cases the
      transferindex for IGM was higher than for IGG1 or IGE.

PMID- 9618988
TI  - [Veterinary surgeon Gottfried Carl Haubner (1806-1882)--promoter of scientific
      animal nutrition].
AB  - The veterinary surgeon G. C. HAUBNER (1806-1882) was teacher for veterinary
      science at the Royal prussian academia for agriculture in Eldena near Greifswald
      (1836-1852) and at the royal school of veterinary science in Dresden (1853-1879).
      He stimulated animal nutrition in different ways. First of all he disclosed the
      theoretical gaps in the field of animal nutrition during the first half of the
      19th century, furthermore he transferred the knowledge in agriculture chemistry
      and animal physiology to feeding praxis and altogether he favoured the transition
      from the empirical to the scientific based animal nutrition, last not least by
      starting exactly planned and practiced feeding experiments (s. Table 2). Most
      remarkable are his very early work on digestion physiology in ruminants (1837),
      his proof (1854), that fiber is digestible in ruminants or horses as well as his
      investigations on nutrition related diseases in cattle (smelting-house-smoke- and
      deficiency-diseases).

PMID- 9618989
TI  - [Ultrasonographic examination of the placentoma development in pregnant sheep].
AB  - The aim of this study was to determine the in vivo development of the placentome
      diameter during the pregnancy in sheep. 32 ewes of four different breeds were
      involved. After the first detection of the placentomes (28 day p. c.) the ewes
      were scanned by transrectal ultrasound (Aloka SSD 500, 5 MHz linear probe) in a
      standing position every second or third day until day 50 p. c. and after the
      every week until parturition. The maximum diameters of 10 placentomes were
      measured. The placentome diameter increased rapidly until the middle of the third
      pregnancy month followed by a slight decrease. Between the 110th day p. c. and
      the parturition the diameter was nearly constant, but 40% of the animals showed a
      second increase at this time. The placentome diameter could be a good mark to
      describe the function of the placenta in sheep but it is only stipulated fit for
      the diagnosis of the state of the pregnancy.

PMID- 9618990
TI  - [The National Academy of Medicine, continuing medical education and certification
      of physicians].

PMID- 9618991
TI  - [Social responsibilities of medical schools].

PMID- 9618992
TI  - [Small-diameter portosystemic shunts: indications and limitations].
AB  - Low diameter porto-systemic shunts for the treatment of portal hypertension
      bleeding have emerged as a consequence of the technical development of vascular
      grafts (PTFE) that allow the use of a narrow lumen. The experience with this kind
      of operation at the Instituto Nacional de la Nutricion Salvador Zubiran, Mexico
      City during a 6-year period is reported. There were twenty-seven patients with
      good liver function (Child-Pugh A-B) were operated or electively, average Age
      47.5 years (range 17-71), twenty three patients with liver cirrhosis, one with
      portal fibrosis and three with idiopathic portal hypertension. Operative
      mortality: 4%. Rebleeding: 14%. Postoperative encephalopathy was observed in 14
      of 27, three of them being grade III-IV (11%). In the remaining 11 cases, it was
      mild and easily controlled. Postoperative angiography showed shunt patency in 81%
      of the cases; in 33% of the cases, portal vein diameter reduction was shown, as
      well as two cases with portal vein thrombosis. In 77% of the cases, adequate
      postoperative quality of life was observed. Survival (Kaplan-Meier): 86% at 12
      months and 56% at 60 months. These kinds of shunts are a good alternate choice
      for patients considered for surgery, in which other portal blood flow preserving
      procedures (selective shunts, devascularization with transection) are not
      feasible.

PMID- 9618993
TI  - [Long-term results of 2 therapeutic protocols in children with acute
      lymphoblastic leukemia of usual risk. Experience at the 20th of November National
      Medical Center].
AB  - The purpose of this study is to know the disease-free survival in children with
      acute lymphoblastic leukemia (ALL), submitted to two therapeutic programs.
      Habitual risk was defined as age older than 2 and younger than 10 years, without
      neurological, mediastinal or testicular infiltrations, leukocytes < 25 x 10(9)/l
      and morphologic cell type distinct of L-3. The first group (LAL81) included 30
      patients, from 1981 to 1986, and they received: induction with vincristine (VCR)
      and prednisone (PDN); consolidation with mercaptopurine (MP), cytosine
      arabinoside (ARA) and doxorubicin (DOX); prophylaxis to the central nervous
      system (CNS) with radiotherapy and methotrexate (MTX)-ARA-hydrocortisone (HDR)
      intrathecal, and maintenance with MP and MTX. In the second group (LAL87), 28
      patients were included from 1987 to 1993. They received: induction with VCR, PDN
      and lasparaginase (ASP); consolidation with MP, ARA, DOX, carmustine (BCNU) and
      cyclophosphamide (CFA); prophylaxis to the (CNS) with intrathecal MTX-ARA-HDR,
      and maintenance with MP and MTX. There was just one therapeutic failure. In the
      LAL81, protocol 11 relapses and 9 in LAL87 (p = 0.71) were observed. Of these,
      two in each group went to the CNS. The disease-free survival in LAL81 was 0.39 at
      14 years; in LAL87, was 0.53 at 8 years (p = 0.62).

PMID- 9618994
TI  - [Neurological and psychological sequelae in children with acute lymphoblastic
      leukemia who had received radiotherapy and intrathecal methotrexate].
AB  - Our objective was to compare the neurologic and psychological sequelae of
      children with acute lymphoblastic leukemia (ALL) after three or more years
      without antineoplasic treatment who underwent cranial irradiation plus
      intrathecal methotrexate (Group 1) or just intrathecal methotrexate (Group 2). In
      both groups, a neurologic evaluation, electroencephalogram (EEG) and cranial
      computed tomography (CCT) were performed. Intellectual quotient and the Bender
      test were done for the psychological evaluation. Investigators did not know the
      kind of treatment of each patient. STATISTICS: Fisher's exact test and Mann
      Whitney U. There were fourteen patients in group 1 and eight patients in group 2.
      Intellectual quotient was statistically lower in the first group (median 83.5)
      than in the second (90.5). Neurologic impairments were found in one patient of
      each group, alterations of the EEG were found in 6 and 4 in group 1 and 2,
      respectively, and in the CCT of two patients in group 2 without statistical
      difference. Children with ALL after cranial irradiation have a greater alteration
      of intellectual performance than children with intrathecal methotrexate.
      Neurologic alterations were seen in both groups.

PMID- 9618995
TI  - [Immediate-acting oral morphine sulfate in patients with cancer pain].
AB  - In this article, we describe our experience with oral morphine for the treatment
      of patients with cancer pain who were referred to a Palliative Care Unit.
      Morphine was used in 3,399 days treatment with an average of 65 days per patient.
      In 50 patients (96%), there was a decreased intensity of pain from severe (Visual
      Analogue Scale average (VAS) 8.7) to mild (VAS average 1.9). Daily average dose
      was 95.6 mg. Only 26 patients (50%) required an increase in dosage. The side
      effects were minimal and controllable. Even though most authors recommend
      morphine q4h, in our population q6h was enough to achieve pain control in 83% of
      patients. It should be known by the medical population that morphine is essential
      therapy for pain in cancer patients. This study confirms that morphine is an
      excellent drug for the control of pain in cancer patients, with minimal dosages
      and controllable side effects.

PMID- 9618996
TI  - [Generics as therapeutic resources].

PMID- 9618997
TI  - [Neuronal migration disorders].
AB  - Neuronal migration disorders represent a group of congenital nervous system
      malformations that affect the process whereby millions of neuroectodermic cells
      move from germinal matrix to the loci, where they will reside for life. They
      produce important changes in cytoarchitecture, lamination and normal neuronal
      physiology, particularly in cerebral cortex. These disorders appear as sporadic
      cases, genetically determined or caused by external agents as infections,
      intoxications and radiations, etc. The better identified nosological entities
      include: schizencephaly, lissencephaly, pachygyria, polymicrogyria, neuronal
      heterotopias and agenesis of corpus callosum. Patients usually present early
      symptoms and signs of disease and epilepsy is a dominant manifestation. By means
      of studies of craneal computed tomography (CCT), magnetic resonance (MR),
      positron emission tomography (PET), single-photon emission computed tomography
      (SPECT) and immunohistochemical and Golgi studies (IHG), it has been recently
      shown that nervous system dysgenesis can be a frequent cause of many refractory
      epilepsies and epileptic syndromes considered as cryptogenic. When these
      disorders are associated with dismorphic stigmas, genetics syndromes such as
      Miller-Dieker, Zellweger and Aicardi should be suspected.

PMID- 9618998
TI  - [Epistemology and medicine].
AB  - Within a conceptualization concerning the health-disease process as a whole
      (which systematically correlates its biological, psychological, social and
      historical aspects), it becomes very difficult to find something in the universe
      involving humankind, without any direct or indirect relationship with that vital
      process. This fact had expanded medicine toward a very extensive and complex
      field of knowledge and practices. Just considering it from the scientific
      perspective, different and opposing acquaintances and research methods vie with
      each other, equally claiming their own worth and stature within science. Because
      of all this and from its origin, allopathic medicine has required the assistance
      and support of philosophy and, in particular, from one specific branch:
      epidemiology. Nevertheless, since Bacon's empiricism (17th century) and, above
      all, since Comte's positivism (19th century), there had predominated until now
      (Piaget) a scientific current which was the enemy of philosophical thinking. In
      spite of the fact that it constituted, in itself, an epistemological position,
      being generalized also among biomedical scientists, there is in medicine at least
      disdain against the philosophy of science. Nevertheless, it is objectively
      indispensable. So, the present essay is presented in this sense, through the
      analytic characterization of the prototypic epistemologies and their
      relationships with medicine throughout history.

PMID- 9619000
TI  - [Transitory occlusion of the ductus arteriosus using a special catheter to decide
      surgical indications].

PMID- 9618999
TI  - [Considerations concerning the 1st outbreak of poliomyelitis in the city of
      Orizaba, Veracruz].
AB  - The objective is to present some deliberations on the paralytic poliomyelitis
      outbreak in the city of Orizaba, Veracruz. Fifty years after its occurrence, the
      original report of the first paralytic poliomyelitis epidemic in Mexico is
      presented herein. The detailed description of this outbreak by the authors
      reflects the devoted task of public health workers and clinicians who promptly
      identified an abnormal pattern of disease considered exotic in Mexico at that
      time. Unfortunately, this outbreak was the beginning of what proved to be an
      endemic disease with over 9,000 cases being reported in the ensuing ten years;
      some studies place the incidence figures three-to-fivefold higher. Fifty years
      after this outbreak, wild polio virus has been eradicated in Mexico and with it,
      the virtual eradication of paralytic poliomyelitis.

PMID- 9619001
TI  - [Catheterization of the left heart cavity and simultaneous recording of
      electrocardiographic tracings and pressures].

PMID- 9619002
TI  - [Peripheral neuropathy caused by acute arsenic poisoning].
AB  - Although peripheral neuropathy is a fairly common finding in chronic arsenic
      poisoning, little is known about the acute effects of this metal on peripheral
      nerves. This report shows clinical and electrophysiological findings in a patient
      who developed peripheral neuropathy only three days after a high-dose ingestion
      of this metal due to a failed suicide attempt. We speculate that peripheral
      nerves and some cranial nerves can show not only clinical but also subclinical
      involvement that can only be detected by neurophysiological studies.

PMID- 9619003
TI  - [Magnetic resonance in basilar atherothrombosis. Clinicopathological
      correlation].

PMID- 9619004
TI  - [New physiopathological mechanisms in Alzheimer's disease and Down's syndrome].

PMID- 9619005
TI  - [Controversies and advances in the treatment of hyperlipidemias].

PMID- 9619006
TI  - [Addictions in women].

PMID- 9619007
TI  - [The law of human body disposal and organ transplants].

PMID- 9619008
TI  - [Dr. Juan Cardenas y Cardenas. In memoriam].

PMID- 9619009
TI  - T cell receptor gene V alpha and V beta usage in patients with rheumatoid
      arthritis in Taiwan.
AB  - To investigate the correlation of T cell receptor (TCR) genes to rheumatoid
      arthritis (RA) in Taiwan, synovial fluid and peripheral blood were examined
      simultaneously in 14 patients with RA, and peripheral blood only was examined in
      15 healthy controls. RNA was extracted from T cell in synovial fluid and
      peripheral blood, and cDNA was synthesized using the reverse transcription
      method. Then, TCR-V alpha and V beta gene families were determined using the
      polymerase chain reaction and slot blot methods. The numbers of TCR-V alpha and V
      beta families, especially V beta, were decreased in rheumatoid synovial fluid
      compared with numbers found in the peripheral blood of the same RA patients. TCR
      V beta 7 and V beta 8 could be found in the synovial fluid of all patients with
      positive HLA-DR4. However, there was no significant difference in the numbers of
      TCR-V alpha and V beta families in peripheral blood of RA patients and the
      peripheral blood of healthy controls. In conclusion, restricted heterogeneity of
      TCR-V gene, especially V beta, can be found in synovial fluid of patients with
      RA. TCR-V beta 7 and V beta 8 may be related to the pathogenesis of HLA-DR4
      positive RA patients in Taiwan.

PMID- 9619010
TI  - In vitro pulsatile flow visualization on extracardiac conduits for the right
      ventricular outflow tract reconstruction: qualitative considerations.
AB  - Valved homograft conduits play an important role in the right ventricular outflow
      tract (RVOT) reconstruction for the surgical treatment of complex congenital
      heart disease. An excellent immediate rather than long-term outcome could be
      obtained. The hemodynamics for late failure, however, remained unclear. In vitro
      pulsatile flow visualization was not conducted before. A simplified right heart
      duplicator system was set up and driven under physiologic conditions. Polystyrene
      of 0.18 mm in diameter was applied as the tracing particle. Flow characteristics
      of models of normal pulmonary circulation as well as pulmonary artery atresia
      with the RVOT reconstructed utilizing valved and non-valved extracardiac conduits
      were observed. Flow patterns in the normal pulmonary circulatory model were
      mainly of axial flow associated with small scope of flow disturbances. A single
      vortex in the right ventricle was noted in diastole. In the pulmonary artery
      atresia model, a couple of vortexes were found in the right ventricle, a
      secondary flow in the main pulmonary artery, and a stronger secondary flow than
      in the normal pulmonary circulatory model in the two branches in both systole and
      diastole. A secondary flow was found in the proximal, an axial flow was observed
      in the distal portion of the extracardiac conduit with normal bioprosthetic
      valves and a secondary flow was observed in the entire conduit with stenotic
      bioprosthetic valves. The secondary flow intensity became stronger with the
      development of the stenosis. Severe insufficiency occurred in the bileaflet
      ceramic tilting-disc prosthesis during the entire cardiac circle, i.e., the
      prosthesis was in a maximum open position. Severe reverse flow could be found in
      the extracardiac conduit in the deceleration phase. Concavity of the crank shaft
      was found by examination to be filled with tracing particles and the prosthesis
      became stuck. Model of RVOT reconstruction with non-valved conduit yielded
      reverse flow inside the extracardiac conduit as well. Secondary flow may occur in
      normal or diseased extracardiac conduit for RVOT reconstruction. If micro
      thrombus of over 0.18 mm in diameter attached in the concave of the crank shaft
      of a bileaflet tilting-disc prosthesis under a condition of resistance as
      occurred in the present study, the prosthesis may become stuck. Model of RVOT
      reconstruction with non-valved extracardiac conduit yielded reverse flow inside
      the conduit, of which the flow pattern was of greater energy consumption. Thus, a
      non-valved conduit should be avoided in clinical practice as far as possible.

PMID- 9619011
TI  - A generalized consideration of myocardial preservation with cold crystalloid
      versus warm blood cardioplegia in heart valve replacement.
AB  - Continuous warm blood cardioplegia was widely used, as an effective means of
      myocardial preservation, in open heart surgery. The comparisons of myocardial
      protective effects between traditional cold crystalloid and warm blood
      cardioplegia, however, have been based mainly on hemodynamics, cardiac function
      and myocardial metabolism, other than clinical outcome. The present study was
      designed to examine myocardial protective effects by assessing clinical outcome,
      enzyme levels and myocardial cytochemistry. Twenty patients undergoing heart
      valve replacement were divided randomly into two groups: Group I was given
      intermittent perfusion of cold crystalloid (St. Thomas Hospital solution) with
      hypothermic cardiopulmonary bypass (CPB) and Group II was given continuous
      administration of warm blood cardioplegia with normothermic CPB. The groups were
      similar with respect to sex, age, body surface area and preoperative ventricular
      function. Blood samples were obtained from an indwelling radial arterial catheter
      or from the arterial end of the oxygenator. Biopsy specimens from the right
      atrium were obtained immediately before aortic declamping (ischemic period) and
      30 minutes after crossclamp removal (reperfusion period). Serum enzymes,
      including alanine transaminase (ALT), aspartate aminotransferase (AST), lactate
      dehydrogenase (LDH) and its isoenzymes and creatine phosphokinase (CK) and its
      isoenzyme, were determined. Myocardial cytochemistry were chiefly assessed by
      grey-scale image processing of adenosine triphosphatase (ATPase), succinate
      dehydrogenase (SDH) and cytochrome oxidase (CCO) examinations. Relations among
      the results were discussed. Reperfusion time was reduced and ventilation support
      time decreased in Group II (33.50 +/- 3.78 min vs. 25.00 +/- 4.46 min, p < 0.05;
      38.98 +/- 16.55 h vs. 19.84 +/- 1.11 h, p < 0.05). Rates of atrial beating during
      aortic crossclamp and spontaneous recovery to normal sinus rhythm were much
      higher in Group II than in Group I (80% vs. 20%, p < 0.05; 70% vs. 10%, p <
      0.05). Differences in hospital morbidity and mortality between groups were
      nonsignificant. Serum AST, ALT, LDH and LDH1 + LDH2 all showed no significant
      intergroup differences. There was a higher serum CK-MB level with a delayed peak
      in Group II. The cytochemistry activities of ATPase was not different between
      groups and periods and SDH was the highest during reperfusion period in Group I
      and of CCO significantly much promoted in Group II in both periods. Continuous
      warm blood cardioplegia resulted in higher spontaneous recovery to sinus rhythm,
      shorter reperfusion and ventilation support time. Damage to the myocardium,
      skeletal muscle and liver always occur in warm blood cardioplegic patients.
      However, warm blood cardioplegia is still a practical method for myocardial
      preservation in open heart surgery.

PMID- 9619012
TI  - Capability of neurite regeneration of retinal explant from adult rat after optic
      nerve injury.
AB  - Axons of the central nervous system in adult mammals do not regenerate
      spontaneously after axotomy. To understand whether the optic nerve of adult
      mammals loses the intrinsic capability to regenerate after injury, we have
      studied the capability of neurite regeneration of retinal explant from adult rat
      after optic nerve axotomy in vitro. After experimental blunt damage to the optic
      nerve of adult Wistar rat, the retinal explants from three days, one week, two
      weeks and three weeks after axotomy were put in tissue culture to observe the
      neurite growth after four days' incubation. The neurites were identified as
      retinal neuron origin by immunocytochemical staining using monoclonal antibody to
      neurofilament. The results demonstrate that retinal explants from adult rat after
      optic nerve damage have the capability of neurite regeneration; the capability is
      strongest in the group of one week after axotomy of optic nerve, but it decreases
      with passage of the time. On the other hand, the retinal explant from the control
      group of uninjured eye does not regenerate neurite in tissue culture. These
      results indicate that the retinal explant of adult rat has intrinsic capability
      to regenerate after optic nerve injury in vitro, and the capability of neurite
      regeneration decreases after one week post-trauma.

PMID- 9619013
TI  - Surgical outcome of hypertensive putaminal hemorrhage in patients older than 65
      years.
AB  - There is no consensus of opinion on the treatment of hypertensive putaminal
      hemorrhage (HPH), especially in patients older than 65 years. The purpose of this
      study was to study the surgical outcome of HPH in patients older than 65 years
      while considering mortality and activity of daily life. Among eighty-three
      patients aged 65 or older with HPH, fifty-one patients received only medical
      treatment and 32 were operated upon to remove the hematoma. Each patient was
      measured by the intracerebral hemorrhage-intracranial hemorrhage grading scale
      (ICH Grade) which used the sum of eye opening and motor response scores derived
      from Glasgow Coma Scale. The cubic content of the HPH was calculated from
      measurement of maximum width (X), length (Y) and height (Z), and the hematoma
      volume taken as 1/2 that volume (X. Y. Z/2). The acute mortality in surgically
      treated group was 40.6% and three patients died during the follow-up period from
      one to six months after the operation. Determinant for the prognosis was the ICH
      grade and the volume of the hematoma. Patients who returned to ADL 1 and 2 (good
      recovery) after surgical treatment were 40.0% in ICH Grade I, 16.7% in ICH Grade
      II, and 20.0% in ICH Grade III. Among those patients who were in ICH Grade IV,
      none had good recovery. The acute mortality was zero in ICH Grade I, 16.7% in ICH
      Grade II, 40.0% in ICH Grade III, and 62.5% in ICH Grade IV. The crucial size was
      60 ml with a mortality of 77.8% for hematomas larger and 39.1% for hematomas
      smaller than that. From our lim ited experience, we learned that operation in
      elderly patients with HPH was considered only in patients with hematomas between
      20 to 60 ml, with a high operative mortality and only one-fourth having a good
      recovery postoperatively.

PMID- 9619014
TI  - Topical application of clobetasol 17-propionate from various cream bases by using
      Wistar rat as an animal model.
AB  - The effect of clobetasol 17-propionate (CP), a potent corticosteroid,
      participating in various cream bases on the permeation through rat skin was
      tested in vitro. Three commercially available formulations and three cream bases
      prepared in our laboratory according to Pharmacopoeia or registered patent were
      evaluated in this present study. The amount of CP in the receptor phase of
      diffusion cell was negligible in the beginning of administration due to the
      process of saturation of drug in skin reservoir, then the CP molecules pass
      through the skin directly because of the saturation of receptors in skin
      reservoir followed the higher flux of CP in the later period. It was suggested
      that the incorporation of penetration enhancers was the possible reason mainly
      controlling the flux of CP creams. Nevertheless, CP residue in skin and the lag
      time of formulations prepared in our laboratory were not significantly higher
      than those of commercial ones, which indicated penetration enhancer could not
      dominate the local pharmacological effectiveness of CP though they played a main
      part on the skin penetration capacity of formulations. The antiinflammatory
      activity of CP was assessed in the ear of Wistar rat. According to the result of
      antiinflammatory activity, all formulations showed significant inhibition on
      oedema suggesting the role of drug itself may be more important than that of
      vehicle in controlling the therapy efficacy.

PMID- 9619015
TI  - A study of central and peripheral nerve conduction in patients with primary
      hypothyroidism: the effects of thyroxine replacement.
AB  - Somato-Sensory Evoked Potential (SSEP) and Peripheral Nerve Conduction (PNC)
      studies were performed in twenty patients with primary hypothyroidism to
      elucidate the changes of central and peripheral nervous systems in hypothyroid
      state and the effects of thyroxine replacement. Before thyroxine replacement
      therapy, eleven patients had significantly delayed SSEP (prolonged latencies of
      N9, N13, or N20), and only three patients had prolonged central conduction time
      (between N13 and N20). PNC abnormalities with decreased conduction velocity and
      diminished amplitudes were found in fourteen patients. After thyroxine treatment,
      both SSEP and PNC studies demonstrated significant improvement and paralleled the
      clinical neurological amelioration. The central and peripheral conduction
      velocities returned to normal limits, while the abnormality in amplitude still
      persisted. There were also discrepancies between SSEP and PNC studies in both the
      abnormality pattern and the recovery potential. Our observations may suggest:
      firstly, both the SSEP and PNC studies may be useful, alternative tools in
      monitoring the neurological disorders in hypothyroidism; and secondly, the
      pathogenesis of central and peripheral nervous dysfunction in hypothyroidism may
      be via different mechanisms.

PMID- 9619016
TI  - Entrapment of index flexor digitorum profundus and median nerve: an unusual
      complication of distal radial fracture--a case report.
AB  - A case of index flexor digitorum profundus and median nerve entrapment by bony
      fracture after reduction as a complication of distal radial fracture in an 11
      year-old male is described. After release of tendon and nerve the patient had a
      good functional result.

PMID- 9619017
TI  - Torsion of a malignant undescended testis.
AB  - Cryptorchid testis have a greater risk of malignant change than do normally
      descended testis. The undescended testis would also be susceptible to torsion by
      the mechanism of increase in testicular size. A 36-year-old man of torsion of
      malignant undescended testis is presented. He was diagnosed as having
      incarcerated inguinal hernia on his first visit to general surgeon due to acute
      left lower abdominal pain. At laparotomy, a 7.5 x 5.5 x 3.0 cm3, greyish tan
      color mass was found. The pathological diagnosis is choricarcinoma and teratoma,
      mixed germ cell tumor. We would emphasise that in any patient presenting with
      acute abdominal symptoms and an absent scrotal testis, the possibility of a
      complication of torsion of undescended testis should be considered.

PMID- 9619018
TI  - Keratomycosis with an unusual clinical manifestation--a case report.
AB  - We report a case of keratomycosis which had recurrent, deep stromal infiltration
      and an endothelial plaque for half a year after the original corneal foreign body
      injury. The subject had an unusual clinical picture of deep corneal infiltration
      and later hair-like material growing from the endothelial plaque into the
      anterior chamber. Repeated corneal scrapings for smears and cultures all showed
      negative during the initial treatment. We tried anterior chamber paracentesis and
      endothelial aspiration and got a positive finding of Cladosporium infection. This
      case is presented because of the difficulty of diagnosis and management of fungal
      keratomycosis.

PMID- 9619019
TI  - [Morphometry using laser light in ophthalmology].

PMID- 9619020
TI  - [High-speed recording of fluorescein fundus angiography using an argon laser as
      the illumination source].
AB  - We constructed a new fluorescein fundus angiography system using a speedy and
      sensitive fundus camera and an argon laser apparatus as the illumination source.
      The system consists of a fluorescein fundus camera, a high-speed camera, a
      digital recorder, an argon laser apparatus, and a cathode ray tube(CRT)monitor.
      The frame speed was 200 frames/s. It was possible to record high speed
      fluorescein angiography with lower illumination by using an argon laser as the
      illumination source. This system allowed us to measure the rate of blood flow in
      the retinal vessels because it easily detected the dye front in the retinal
      vessels.

PMID- 9619021
TI  - [Pterygium and mast cells--expression of basic fibroblast growth factor increase
      in mast cells of the pterygium].
AB  - We examined the expression of basic fibroblast growth factor (bFGF) protein
      immunohistochemically, and bFGF specific messenger RNA (bFGF-mRNA) by in situ
      hybridization in the excised tissue of 5 cases of pterygium and 4 cases of normal
      conjunctiva. Immunohistochemical staining for bFGF showed strong positive
      staining in metachromatic mast cells stained with toluidine blue in the pterygium
      and in normal conjunctival specimens. The mean metachromatic mast cell count in
      pterygium specimens was increased significantly when compared with normal
      conjunctiva. In mast cells, bFGF positive rate was 84% in pterygium specimens,
      and 69% in normal conjunctival specimens. In situ hybridization indicated that
      the bFGFmRNA is located in most mast cells in pterygium specimens, but in only a
      few mast cells in normal conjunctival specimens. These results suggest that
      increased bFGF protein produced and stored by mast cells in the pterygium may
      contribute to its progression.

PMID- 9619022
TI  - [Measurement of retinal blood flow velocity by scanning laser ophthalmoscopic
      fluorescein fundus angiography in experimental retinal vein obstruction].
AB  - To study the role of arterial blood dynamics in the thrombogenesis of thrombin
      induced experimental retinal vein obstruction, the retinal blood flow velocity
      was evaluated using scanning laser ophthalmoscopic fluorescein videoangiography
      in an experimental rabbit retinal vein obstruction model. Retinal vein
      obstruction was made by transadventitial direct instillation of thrombin to the
      retinal vessels from the vitreous side. The blood flow velocity in the retinal
      artery and vein was estimated by measuring the passing velocity of the flow head
      of the dye bolus and venous filling time, respectively. 23 animals were treated
      with thrombin and compared with 18 controls not treated. In the control group
      retinal artery blood flow velocity and retinal venous fluorescein filling time
      was 5.3 +/- 1.1 mm/sec (mean +/- standard deviation) and 6.2 +/- 1.2 sec,
      respectively. In the treated group the values were 5.7 +/- 1.3 mm/sec and 5.8 +/-
      1.0 sec before the thrombin administration, and 3.0 +/- 0.9 mm/sec at 24 hours
      after its administration, and 5.7 +/- 2.0 sec and 4.0 +/- 1.5 mm/sec and 4.5 +/-
      1.4 sec at 48 hours after the administration. These results indicate that a
      decrease in retinal artery blood flow velocity is strongly involved in the
      thrombogenesis in thrombin-induced experimental retinal vein obstruction.

PMID- 9619023
TI  - [Influence of light scattering in the opaque lens on the ability to focus-
      examination utilizing opacified model lenses].
AB  - In order to objectively evaluate the relationship between the quality of images
      which will be reflected on the retina, through opaque lenses and the grade of
      opacification, model lenses of nuclear cataract and subcapsular cataract were
      manufactured. The nuclear cataract model lenses were made of
      polymethylmethacrylate (PMMA) with and without a cut off wavelength below 380 nm.
      The lens shape was the biconvex intraocular lens (IOL) type and the opacification
      was achieved by polymerization of both hydrophile and lyophobic monomers. The
      model of subcapsular opacification was composed of ultraviolet (UV)-cut IOL and a
      hard contact lens (HCL). The HCL was attached behind the IOL and whitish
      corpuscles (T1O2, mean diameter of particle = 0.2 micron) were inserted into the
      gap between the lenses. Utilizing a still camera with 35 mm film, images were
      photographed through the nuclear opacified model lenses and evaluated. The model
      of the subcapsular opacified lens was examined by a simulation camera (CCD) in
      which the lens was held in water. The image quality obtained from the non-UV
      absorbed nuclear opacification type lens was markedly poor compared with that
      from the UV absorbed type lens. Although image contrast became worse with
      increased nuclear opacification, the worsening of image quality was slight in the
      opacified lens with a 20% reduction of light transmission. It was even possible
      to recognize photographed subjects through an opacified lens with 60%
      transmission. Images through the subcapsular opacified model lenses were not
      influenced by the opacified area in the models with up to 130 cct light
      scattering intensity at the central part of opacification. Although the study
      aimed to simply simulate images reflected on the retina through two types of
      cataractous lenses, the results obtained showed useful objective information
      concerning images seen through cataractous eyes.

PMID- 9619024
TI  - [5-S-cysteinyldopa as a tumor marker for primary uveal malignant melanoma].
AB  - The clinical significance of 5-S-cysteinyldopa (5-S-CD), a major intermediate in
      melanin synthesis, was evaluated as a potential diagnostic tumor marker for uveal
      melanoma. Serum concentrations of 5-S-CD in 6 out of 7 patients with uveal
      melanoma in the absence of extraocular metastases were close to those of
      controls. In contrast, serum concentrations of 5-S-CD were found to be elevated
      in 3 patients with systemic metastases of melanoma. In addition, 5-S-CD in
      intraocular fluids, including both aqueous and vitreous humor, was elevated in
      patients with uveal melanoma regardless of the presence or absence of systemic
      metastases. These results suggest that 5-S-CD in the intraocular fluid may serve
      as a useful biochemical marker for the diagnosis of uveal melanoma.

PMID- 9619025
TI  - [Estimated prevalence rate of HTLV-I uveitis in Chikugo].
AB  - To estimate the prevalence rate of human T-cell lymphotropic virus type 1 (HTLV
      I) uveitis, an epidemiological survey was carried out in the Chikugo District of
      Fukuoka Prefecture between 1 September and 31 October 1995. The survey was done
      by sending questionnaires on uveitis patients to all ophthalmological institutes
      in the district and measuring the serum antibody to HTLV-I. The recovery rate of
      the survey was 39 of 48 institutes (81.3%). A total of 357 patients with uveitis
      were reported in the survey, of whom 317 (88.8%) were tested for their
      seropositivity to HTLV-I. Among them, 18 patients were counted as having HTLV-I
      uveitis (HU) on 1 October 1995. Based on these data together with the age- and
      sex-specific population of HTLV-I carriers in the Chikugo District, it was
      estimated that the crude prevalence rates of HU per 100,000 HTLV-I carrier
      population were 58.6 in males, 152.0 in females, and 112.2 in both sexes. The
      prevalence rate of HU was slightly higher than that of HTLV-I associated
      myelopathy.

PMID- 9619026
TI  - [Diagnostic capabilities of a classification program of the Heidelberg retina
      tomograph for early glaucomatous changes].
AB  - We investigated the diagnostic capabilities of a new glaucoma diagnostic softwave
      (classification program) of the Heidelberg retina tomograph for early glaucoma.
      Thirty eyes of 30 patients with early glaucoma (average visual field mean
      deviation = -3.7 dB) and 30 eyes of 30 normal subjects were enrolled. The
      criterion for early glaucomatous change was a visual field defect appearing
      earlier than Aulhorn classification stage II without considering the disc
      configuration. The diagnostic ability of three glaucoma specialists for the same
      eyes was evaluated using the Heidelberg retina tomograph analysis map. The
      agreement of two or three glaucoma specialists was accepted as the final
      judgment. Sensitivity, specificity, and diagnostic precision were calculated for
      all evaluations. The agreement between the classification program and glaucoma
      specialists was calculated with kappa statistics. Sensitivity, specificity, and
      diagnostic precision of the classification program were 80%, 83% and 82%,
      respectively. Those of the by glaucoma specialists were 83%, 90% and 87%,
      respectively. The agreement between the classification program and glaucoma
      specialists was excellent (kappa 0.73, % agreement 86.7%). The classification
      program will aid the diagnosis of early glaucomatous damage with high sensitivity
      and specificity.

PMID- 9619027
TI  - [Reproducibility and wave analysis of multifocal electroretinography].
AB  - We studied the reproducibility of multifocal electroretinography by repeated
      measurements in normal subjects. We also analyzed the amplitude and implicit time
      of the waves. Nine healthy eyes including myopic cases (-4.1 D on average) of 9
      normal males, aged 19 to 42 years, were the objects of study. We used a (Visual
      Evoked Response Imaging System III (VERIS III), by TOMEY Corp.) for multifocal
      electroretinography. Each eye was examined 4 times on different days. The
      stimulus elements consisted of 103 hexagons. The net recording time was 4
      minutes. We used the coefficient of variation (standard deviation/average) of 4
      measurements of response density as index of reproducibility. Poor fixation and
      blinking were important factors that affected the reproducibility. In all the 9
      eyes, reproducibility of multifocal electroretinography, expressed as average of
      the coefficient of variation of all regions, was 22% on average. In 6 eyes with
      good fixation and without blinking, the reproducibility was 15% on average. In 6
      eyes with good reproducibility, we analyzed three parameters of the focal
      response waves: all traces, quadrants and rings, as well as the amplitude and
      latency of the waves. These data served as controls. Our studies showed that the
      response density correlated closely with the amplitude and not with the latency
      in normal subjects.

PMID- 9619028
TI  - [The clinical features of 9 cases of intraocular malignant lymphoma of
      oculocerebral origin].
AB  - We reviewed a series of 13 eyes in 9 cases of intraocular lymphoma with or
      without intracranial involvement during the past 15 years. The cases were
      characterized by moderate or no inflammation in the anterior ocular segment and
      by the presence of vitreous opacity and fundus lesions. Contrary to the accepted
      view that this disease simulates uveitis with various manifestations, the fundus
      lesions in the present series showed disseminated or tumorous subretinal lesions
      suggestive of proliferation of tumor cells. Only a few cases showed retinal
      vasculitis or retinal exudates. Electrooculograms showed findings suggestive of
      widespread impairment of the retinal pigment epithelium. Because of poor
      prognosis and sensitivity to radiation, we advocate early diagnosis and treatment
      for this disease.

PMID- 9619029
TI  - Analysis of lobectomy for small peripheral lung cancer supports extended
      segmentectomy.
AB  - We reviewed the records of 53 patients who underwent lobectomy for peripheral non
      small cell lung cancer under 2 cm in diameter and established a rationale for
      segmentectomy with intraoperative lymph nodes dissection (extended
      segmentectomy). Five patients (9.4%) had intrapulmonary metastases. Nodal status
      was N0 in 34 patients (64.2%), N1 in 7 (13.2%), and N2 in 12 (22.6%). Based on
      examination of intraoperative frozen sections, 31 patients lacking lymph node
      metastases and visceral pleural involvement could have been candidates for
      extended segmentectomy. Twenty-seven had stage I disease on postoperative
      examination of paraffin-embedded sections. Of the remaining 4 patients, 1 had
      involvement of intrapulmonary lymph nodes in the segment where the primary lesion
      originated. Another patient had involvement only at the first mediastinal lymph
      node level, representing a "skipping metastasis". The remaining 2 patients had no
      lymph node involvement, but had intrapulmonary metastases in the same segments as
      the primary lesion. We conclude that an extended segmentectomy may be as
      effective as lobectomy for treatment of peripheral non-small cell lung cancer
      under 2 cm in diameter without evident lymph node involvement.

PMID- 9619030
TI  - Mitral reoperation via right thoracotomy in a patient with pulmonary
      hypertension.
AB  - A 62-year-old woman with pulmonary hypertension underwent mitral valve re
      replacement through right thoracotomy. Severe adhesion occurred to the right
      lung. During pleural dissection the lung collapsed under single-lung ventilation,
      rapidly elevated pulmonary vascular resistance caused hemodynamic instability.
      When pulmonary hypertension is preoperatively present, this approach under single
      lung ventilation is not recommended.

PMID- 9619031
TI  - [Some techniques for the correction of the congenital heart disease with
      autologous flap].
AB  - 14 living flaps in 8 children were used to repair for the congenital heart
      disease, because artificial material and xeno grafts were shrunk in growing
      children but living flaps were going to glow with children. It were possible to
      use the living flaps to reconstruct of pulmonary outflow in truncus arteriosus,
      for septoplasty in partial anomarous of pulmonary venous return and
      reconstruction of unloofed coronary sinus in endocardial defect with triatriatum
      and intraatrial tunnel in TCPC or Fontan type operation.

PMID- 9619032
TI  - [Resection and reconstruction of sternum].
AB  - In case of sternal resection, it is necessary to preserve bone material
      indispensable for the stability of the anterior chest wall and air tightness of
      the thoracic cavity, and the support of the chest wall integrity must be restored
      by some means. Various techniques have been applied to the reconstruction of the
      chest wall following resection. During the last 10 years, we have performed
      reconstructive operation for 6 cases of the chest wall following resection of the
      sternum in recurrent cases of breast cancer or invaded case of primary breast
      cancer. In these patients, the chest wall was reconstructed using a rib
      latissimus dorsi osteomyocutaneolus flap or a latissimus dorsi myocutaneous flap.
      The sternum was totally resected in 3 cases, and in all 3 cases, reconstructed
      using a rib-latissimus dorsi osteomyocutaneous flap. Although postoperative
      pulmonary function decreased, all cases could be relieved from endotracheal
      intubation within 17 hours after operation, and had no problems in activities of
      daily living or occurrence of chest flailing or paradoxical movement of the
      chest. An artificial material (expanded polytetrafluoroethlene patch) was used in
      only one patient for the reconstruction of the osseous thorax, but this case
      developed infection during postoperative chemotherapy. After this experience, we
      used only biological materials for the reconstruction of the chest wall and
      postoperatively performed radiotherapy and/or chemotherapy on all cases. We have
      observed no flap infection or detachment since then. One characteristic of using
      the latissimus dorsi myocutaneous flap is that it is easily elevated and rarely
      causes serious postoperative esthetic or functional problems. The flap is also
      easily utilized to reinforce the osseous thorax because ribs immediately below
      the latissimus dorsi muscle are readily mobilized as a pedicle graft.
      Reconstruction of the chest wall following resection of the sternum, described in
      this report, allowed us to perform radiotherapy and/or chemotherapy without
      serious postoperative complications on the cases relapsing after treatment of
      breast cancer. The 2-year survival rate is 50% and one of these cases survived up
      to 10 years after resection of the sternum. Thus we prefer to perform resection
      of the sternum for sternal recurrence of breast cancer if there are no metastatic
      lesions in other organs.

PMID- 9619033
TI  - [Thoracoscopic surgery for diagnosis of interstitial pneumonia special reference
      to medicoeconomical effect].
AB  - We compared thoracoscopic surgery (TS) and open thoracotomy for the diagnosis of
      interstitial pneumonia. Intraoperative blood loss and duration of postoperative
      chest drainage were significantly less with TS than with thoracotomy. The length
      of postoperative hospital stay and social insurance costs with TS was
      significantly less than with thoracotomy. These results show that TS for the
      diagnosis of interstitial pneumonia is superior to open thoracotomy in terms of
      surgical stress and cost.

PMID- 9619034
TI  - [Pulmonary artery sling with tracheal stenosis--primary repair in infancy].
AB  - Between 1984 and 1996 five infants underwent surgical repair of pulmonary artery
      sling associated with severe congenital tracheal stenosis. All infants had
      symptoms of severe respiratory distress and three of them required ventilator
      support preoperatively ages ranged from 2 to 11 months (mean age 6 months).
      Complete tracheal rings were present in all patients as an associated lesion and
      right upper lobe tracheal bronchus in 3 patients. The length of tracheal stenosis
      ranged from 18 to 45 mm (median 40 mm). Three had associated intracardiac
      anomalies (Scimitar syndrome (1), VSD (1), double-outlet right ventricle with VSD
      (1), double-outlet right ventricle with pulmonary hypertension (1)). Surgical
      intervention was carried out through a right thoracotomy (1) or median sternotomy
      (4). Cardiopulmonary bypass (CPB) was used in 3 patients and extracorporeal
      membrane oxgenator (ECMO). In 1. All infants had reimplantation of the left
      pulmonary artery into the main pulmonary artery left anterior to the trachea.
      Four patients underwent simultaneous tracheoplasty using costal cartilage grafts
      and one had complete resection of obstructed trachea between the right upper lobe
      tracheal bronchus and carina. The length of resected trachea was about 30% of the
      entire length of the trachea. Three infants underwent simultaneous intracardiac
      repair. There was no hospital death. All were weaned from ventilatory support and
      extubated on 1 to 16 months (mean 4, 5 months) postoperatively. AS an additional
      procedure, aortopexy, removal of granulation tissue or balloon dilatation of the
      trachea were carried out in one patient each following tracheoplasty using
      cartilage grafts. There was one late death at 1 year postoperatively. Three of 4
      survivors are doing well with no stridor. We adonostridor. We adovocate 1) early
      aggressive primary repair of pulmonary artery sling with tracheal stenosis, 2)
      concomitant repair of tracheal lesion and intracardiac anomalies whenever
      possible, 3) application of CPB or ECMO to avoid cumbersome intubation technique,
      and 4) utmost effort to perform tracheal resection and end-to-end anastomosis.

PMID- 9619035
TI  - [Glutamate neurotoxicity during spinal cord ischemia--the neuroprotective effects
      of adenosine].
AB  - Evidence is accumulating that glutamate, a major neurotransmitter, exerts potent
      neurotoxic activity during ischemia. In our laboratory, a delayed-onset
      paraplegia model using rabbits has been developed and described. The severity of
      the ischemic event in this model, i.e., extracellular glutamate overload, is
      believed to influence the etiology of this delayed neuronal dysfunction.
      Adenosine, an endogenous neuromodulator, is released after acute ischemic insult
      and provides neuroprotection by actions on neuronal and glial cells in the still
      viable border zone of the ischemic focus. We hypothesized that the
      neuroprotective action of adenosine is associated with inhibition of glutamate
      neurotoxicity following ischemia. Infrarenal aortic segments from 11 New Zealand
      white rabbits were isolated for 5 minutes and infused at a rate of 2 ml/min.
      Group I (n = 6) received normothermic L-glutamate (20 mM). Group II (n = 5)
      received 75 mg of adenosine and normothermic L-glutamate (20 mM). Neurologic
      function was assessed at 6, 24, and 48 hours after surgery according to the
      modified Tarlov scale, After 48 hours, the rabbits were euthanized and their
      spinal cords were harvested for histologic examination. The neurologic function
      of three rabbits in group I showed acute paraplegia and the other three showed
      delayed-onset paraplegia, whereas all group II animals and nearly intact
      neurologic function. Histologic examination of spinal cords from rabbits in group
      I showed evidence of moderate spinal cord injury with central gray matter and
      adjacent white matter necrosis and axonal swelling, whereas spinal cords from
      group II revealed no evidence of cord injury. Adenosine A1-receptor activation is
      suspected to reduce excitatory amino acids by controlling the activation of the
      voltage-dependent NMDA receptor. These results indicate that the neuroprotective
      effect of adenosine is associated with inhibition of glutamate neurotoxicity,
      which initiates a deleterious cascade of biochemical events that ultimately
      result in delayed-onset paraplegia.

PMID- 9619036
TI  - [Efficacy and safety of a single oral dose of pilsicainide in supraventricular
      arrhythmia after coronary artery bypass grafting].
AB  - We evaluated the efficacy and safety of administration of a single oral dose of
      Pilsicainide, a class Ic antiarrhythmic agent, in 34 patients (26 men, 8 women,
      age from 48 to 81, mean age 66 +/- 8 years) who developed supraventricular
      arrhythmia after coronary artery bypass grafting (CABG). A total of 42 episodes
      of postoperative supraventricular arrhythmia, with the majority occurring 2-4
      days after CABG, were classified as follows: paroxysmal atrial fibrillation, 34;
      paroxysmal atrial flutter, 6; and sinus tachycardia, 2. Sinus rhythm was restored
      in 32 episodes (78%) by treatment with oral pilsicainide given in a single dose
      of 50 ro 100 mg. Successful conversion was obtained within 90 minutes in 44% and
      3 hours in 56% of episodes, with a mean conversion time of 119.2 +/- 107.5
      minutes after the administration of pilsicainide. The mean conversion times
      tended t highlight the difference between the 50 mg and 100 mg doses, but this
      difference was not statistically significant (p = 0.053). The ventricular rate
      was significantly reduced from 123.3 +/- 29.5 beats/min to 85.6 +/- 19.9
      beats/min (p < 0.0001), however no significant changes in blood pressure or no
      significant side effects were observed. The results of the present study suggest
      that a single oral dose of pilsicainide, administered for its favorable
      pharmacokinetic profile and lack of hemodynamic side effects, is a valuable drug
      for converting supraventricular arrhythmia to sinus rhythm in most patients after
      CABG.

PMID- 9619037
TI  - [Decreasing sarcoplasmic reticular calcium gives rise to myocardial protection-
      the effect of thapsigargin for myocardial protection under conditions of
      normothermia].
AB  - Deceasing sarcoplasmic reticular (SR) calcium may contribute to the myocardiac
      protection against ischemia and reperfusion-induced injury. Therefore, using the
      isolated working rat heart model, we investigated the effect of Thapsigargin (TH)
      induced SR calcium diminution on the myocardial protection when added either
      before onset of ischemia or at time of reperfusion under conditions of
      normothermic ischemia. Hearts (n = 6/group) from male Wistar rats were
      aerobically (37 degrees C) perfused (20 min) with bicarbonate buffer. In the
      experimental protocol A, this was followed by a 3 min infusion of St. Thomas'
      Hospital cardioplegic solution No. 2 (STS) containing various concentrations of
      TH. Hearts were then subjected to 34 min of normothermic (37 degrees C) global
      ischemia and 35 min of reperfusion (15 min Langendorff, 20 min working).
      Reperfusion cardiac functions at 20 min of working perfusion was measured and
      compared with the preischemia values. STS added to 0.1 and 0.25 mumol/L TH
      improved recovery of aortic flow after 20 min reperfusion from 47 +/- 3% in the
      TH free controls to 62 +/- 3, 63 +/- 2% (n = 6) (p < 0.05). There was no
      difference in creatine kinase (CK) leakage during Langendorff reperfusion between
      the TH treated groups and the control group. In the experimental protocol B, 3
      min of cardioplegia without TH and 34 min of ischemia (37 degrees C) were
      followed by a 10 min Langendorff reperfusion with various concentrations of TH,
      then 10 min Langendroff reperfusion for washing out, and 20 min working
      reperfusion. When TH was added to reperfusate the recovery of aortic flow did not
      change, 0.5 mumol/L TH group had the detelious effect. Thus, TH, when added to
      the cardioplegia, enhanced myocardial protection. We conclude that lessened
      uptake of Ca2+ into sarcoplasmic reticulum by inhibitors of the Ca(2+)-ATPase
      pump can decrease ischemia and reperfusion-induced injury.

PMID- 9619038
TI  - [Aortic regurgitation caused by the proximal dissecting flap invagination to the
      left ventricle].
AB  - A 68-year-old male with sudden back pain and cardiogenic shock status transferred
      to our ward. Transthoracic echocardiography revealed that the abnormal round
      shape string was in the left ventricular outflow tract. The continuity from the
      staring to the aortic valve was unclear. Intimal flap could not be detected at
      the level of the ascending aorta. Color Doppler flow imaging showed that the
      severe AR jet extended into the round string. TEE showed that the intimal tear
      and flap was seen just above the left subclavian artery. Preoperative diagnosis
      was acute Stanford type A dissection and acute severe AR due to the inversion of
      the proximal intimal flap to the left ventricular outflow tract through the
      aortic valve. At operation, the proximal intimal flap was dissected
      circumferentially and was cut all the way around 8 cm above the aortic valve ring
      and was inverted to the left ventricular outflow tract. The aortic valve was
      preserved because of its normal character after exclusion of the proximal intimal
      flap. Ascending and arch replacement was carried out. Postoperative TEE and TTE
      slowed no findings of AR. The patient's postoperative course was uneventful. To
      our knowledge, this is the first reported case that severe AR caused by the
      proximal intimal invagination to the left ventricle.

PMID- 9619039
TI  - [Surgical treatment for a 16-year-old girl with anomalous origin of the right
      pulmonary artery from ascending aorta].
AB  - Anomalous origin of the right pulmonary artery is a rare congenital malformation
      and is usually fatal without early surgical correction. A 16-year-old patient,
      who had received no previous treatment, demonstrated abnormal findings on ECG. On
      cardiac catheterization, the pressure in the normally arising left pulmonary
      artery was found to be greater than the systemic level. Bidirectional shunting
      across a patent ductus was identified and aortography revealed that the right
      pulmonary artery arose from the posterior wall of the proximal ascending aorta.
      The presence of severe pulmonary vascular obstructive disease was anticipated and
      right lung biopsy was performed. The index of pulmonary vascular disease rating
      was 2.8 and the Heath-Edwards classification was grade 3. Consequently, we
      considered that corrective right pulmonary circulation could be maintained after
      correction, and total correction was performed. The postoperative course was
      uneventful and the pulmonary artery pressure reduced significantly. Discussion
      focuses on the surgical indications for such infrequent older cases and we
      conclude that preoperative lung biopsy is useful in identifying severe pulmonary
      vascular disease and evaluating indications for surgery.

PMID- 9619040
TI  - [Congenital bronchial atresia complicated with severe cough--a case report].
AB  - A 37-year-old woman presented severe cough for several years. Chest X-ray showed
      an abnormal shadow in the right upper lung field. That was absent but hyperlucent
      before onset. Chest CT scan revealed a mass shadow with mucoid impaction in the
      right S2. Thoracoscopic right upper lobectomy dramatically improved her
      complaints. Histological examination revealed the dilated bronchus containing
      mucoid impaction and confirmed a diagnosis of congenital bronchial atresia. It
      was suggested that organizing pneumonia resulting from repeated infection caused
      severe cough. Thoracoscopic surgery for congenital bronchial atresia should be
      recommended in young patients.

PMID- 9619041
TI  - [Diagnostic role of skin manifestation].
AB  - Onto the common integument, as the largest "screen" of our organism, symptoms of
      numerous inner-organic diseases may exert projection. Of them important
      diagnostic conclusions are to be drawn, among which several ones are essential in
      modern medicine as well. Set out from symptom samples observed on skin, cutaneous
      symptoms and connections having recent diagnostic significance come to our
      demonstration.

PMID- 9619042
TI  - [Prenatal diagnosis of tricuspid atresia].
AB  - Tricuspid atresia is the third most common cyanotic cardiac malformation, seen in
      1 per cent of children with congenital heart disease. It occurs in 4-5 per cent
      of congenital heart defects diagnosed prenatally, this difference is a
      consequence of a high percentage of intrauterine death these severely ill
      fetuses. Initial surgical treatment is palliation, usually with aortopulmonary
      shunt. Definitive treatment is the Fontan operation, when the systemic venous
      return is connected directly to the pulmonary tree. Five-year survival for
      liveborn patients is 50, but for prenatally diagnosed fetuses only 20%. In
      Hungary there is only a few survivor. Authors have diagnosed 20 tricuspid
      atresias during a five-year period by fetal echocardiography. In two cases the
      postnatal findings were: normal tricuspid valves, univentricular atrio
      ventricular connection and stenosis of the pulmonary artery, in one case
      dysplastic tricuspid valves, hypoplastic right ventricle and stenosis of the
      pulmonary artery. Authors summarise their experiences with prenatal
      echocardiography of tricuspid atresia and describe characteristic signs could be
      found by routine ultrasound screening of this severe cardiac malformation.

PMID- 9619043
TI  - [Computerized speech recognition-based endoscopic findings].
AB  - Discrete, Hidden Markov model based speech recognition and phoneme based speech
      synthesis techniques were applied for gastroscopy reporting and machine control.
      The authors developed a special program for grammatical analysis of the
      sentences. Altogether 100 patient findings were grammatically analysed. The
      sentences were grouped according to the topographical order of the investigation:
      oesophagus, cardia, fundus, corpus, antrum, pylorus, bulbus, postbulbar section,
      and the pathological findings: erosion, ulceration, malignancy. Speech samples
      from 3 deep voiced male investigators were collected. The recognition rate was
      above 95%. A simulation program was also developed for dictation and controlling
      of the different equipment (monitor, printer, video, endoscope) in the
      gastroscopy laboratory by speech recognition. Speech synthesis was applied for
      the evaluation of understanding. This module artificially synthesizes the answer
      of the system giving backup for the understood information. With additional
      developments the discrete word speech 'recognition' achieved the level of routine
      application in medical reporting. However, ready-to-use developments need the
      joint activity of speech technology and endoscopy industry with end-user teams.

PMID- 9619044
TI  - [The role of elective hemofiltration in the management of sepsis and multiple
      organ failure].
AB  - Septic shock and the multiple organ dysfunction syndrome carries a very high risk
      of mortality. The exact pathomechanism of the development of multiorgan
      dysfunction is yet to be revealed and its treatment remains the biggest challenge
      in intensive care. In order to prevent the development of multiple organ
      dysfunction new therapeutic modalities have been investigated over the last
      years. One promising intervention is the exchange of large volumes of
      ultrafiltrate during haemofiltration termed as "elective" haemofiltration. By
      removing several middle molecular weight inflammatory mediators from the
      circulation, currently thought to be responsible for a number of complications
      due to sepsis, it as been suggested, that it might improve survival in theses
      patients.

PMID- 9619045
TI  - [Experience with percutaneous endoscopic gastrostomy in the nutrition of a
      patient with 3rd and 4th degree facial burns].
AB  - Recovery after thermal injury depends in great proportion on nutrition. A major
      problem is accounted in patients with facial burn, because they can not be
      nourished per vias naturales. Eliminating disadvantages of parenteral nutrition,
      but utilizing the advantages of enteral nutrition, we have tried a new method of
      treatment in a patient whose case is presented. On the second day after injury a
      percutaneous endoscopic gastrostomy was made. On the 7th day after injury and on
      the 4th day from the beginning of enteral nutrition complete intake of food and
      liquid was assured through the percutaneous endoscopic gastrostoma. We had no
      complication related to the gastrostoma. Nutrition through the percutaneous
      endoscopic gastrostoma at our patient provided a "natural" route to assure
      liquid, electrolite and energy balance, prevented atrophy of intestinal mucosa
      and its metabolic and immunologic complications. With the use of percutaneous
      endoscopic gastrostoma the possible complications of central line catheter were
      omitted. Our opinion is that percutaneous endoscopic gastrostomy is a safe and
      effective method for the clinical nutrition of burned patients.

PMID- 9619046
TI  - [Zoltan Rethy. Remembering a district physician].

PMID- 9619047
TI  - [Gyula Sandor Szigeti (1872-935)].

PMID- 9619048
TI  - [Anniversary of catheterization in cardiology (Andreas Ronald Gruentzing)].

PMID- 9619049
TI  - [Angiogenesis, anti-angiogenesis].

PMID- 9619050
TI  - [Genetics of renal tumors].

PMID- 9619051
TI  - [The new pathological anatomy].

PMID- 9619052
TI  - [On the transition of the cadaver from the "opposite" to the "helper" of life].
AB  - Death and corpse were incompatible with god's and family doctor's presence in the
      Greek-Roman world. This incompatibility between life and the death was surmounted
      by the admittance of Saints' bodies in the Churches and believers' burial "ad
      Sanctos". From this, to body's utilization as discloser of the "causae morborum"
      the way was relatively short, culminating in the stage marked by Morgagni's name.

PMID- 9619053
TI  - [Cytogenetic analysis of hypophyseal adenoma. Study of 9 cases and review of the
      literature].
AB  - INTRODUCTION: To the best of our knowledge, no specific chromosomal abnormalities
      have been found in the literature in pituitary adenomas. In the present study, we
      investigated 9 cases of pituitary adenoma and reviewed the current literature.
      MATERIALS AND METHODS: Nine cases of pituitary adenoma have been studied with
      immunohistochemistry and cytogenetic using short-term cultures. RESULTS: All
      tumors had a normal karyotype. Three cases were clinically non-secreting
      adenomas, three cases produced prolactin, two showed growth hormone production
      and one thyroid-stimulating hormone. One of the cases showed dural invasion.
      CONCLUSIONS: We compared our results with those published in the current
      literature. It appears that pituitary adenomas do not have specific numerical and
      structural abnormalities and mostly show a normal karyotype.

PMID- 9619054
TI  - [Flow cytometry sutdy of DNA and cell kinetics in the adenoma- carcinoma sequence
      in the large intestine].
AB  - The quantitation of DNA and growth fraction in the different step from dysplastic
      to neoplastic process in large bowel is the aim of this study. 70 colonic polyps
      were studied. The fresh specimens were processed and DNA analysis was carried out
      using a Partec CA II flow cytometer and the growth fraction was tested with KI-67
      monoclonal antibody. The percentage of S-phase cells has been calculated with the
      Multicycle program. Our results demonstrated that 7 adenomas were tubulo-villous
      with mild dysplasia, 39 with mild-moderate dysplasia, 1 with severe dysplasia, 5
      were polypoid carcinomas, 2 juvenile polyps, 1 polypoid leiomyoma, 1 inflammatory
      fibroid polyps. DNA analysis showed a diploid DNA content in non adenomatous
      polyps, in all adenomas with mild dysplasia, in 37 with mild-moderate dysplasia,
      in 8 cases with moderate-severe dysplasia and 1 cancer. Aneuploidy was discovered
      in 2 cases with mild-moderate dysplasia, in 6 cases with moderate-severe
      dysplasia, in the case of severe dysplasia and in 4 cases of carcinomas. Best
      indexes of linear correlation (Pearson's r) has been found between S-phase and
      DNA index (r = .75) and between S-phase and KI-67 (r = .82). IN CONCLUSION: 1) No
      relationship was found between DNA content and age, sex, size and location of
      polyps. 2) Aneuploidy is strictly related to moderate-severe grade of dysplasia
      therefore it is an important element in the development of adenomacarcinoma
      sequence. 3) DNA-index, S-phase and KI-67 are strictly related.

PMID- 9619055
TI  - [Analysis of the intralaboratory diagnostic variability in the Imola cervical
      screening program].
AB  - The value of the assessment of intralaboratory variability as a method for
      quality control of cervical screening is an ill-defined one. This model has been
      advocated and utilized by some Authors and only indirectly addressed by others.
      In Italy, only occasional studies have been published. The present analysis is
      part of a series of studies for the evaluation and quality control of the
      population cervical screening programme in the area of Imola. The agreement
      between the 5 cytologists was tested over a series of 150 smears selected from
      the routine material. The data were analyzed with the k statistic and the degree
      and direction of discrepancies were assessed by the percent distribution of
      paired diagnoses. The k values for agreement between the 10 possible pairs of
      cytologists varied between 0.25 and 0.49 (average value, 0.37). The indexes for
      agreement as based on three classes ('Negative'/ASCUS + LGSIL +
      HGSIL/'Unsatisfactory') varied from 0.35 to 0.56 (average value, 0.46). The
      cytologist-specific k values (as based on five classes) ranged from 0.29 to 0.43.
      For the observer with the lowest specific coefficient (designated as C4), the
      excess disagreement was restricted to the ASCUS class and the 'Unsatisfactory'
      notation. In particular, C4 diagnosed more often 'Negative' smears (74% vs. 44
      55%) and less frequently ASCUS (11% vs. 22-31%) and 'Unsatisfactory' smears (3%
      vs. 6-11%). ASCUS was the least reproducible diagnosis (k = 0.22). The evaluation
      of the degree and direction of the diagnostic discrepancies between the five
      cytologists showed that the frequency of concordant diagnoses of ASCUS was as low
      as 39.7%. However, the discrepancies were almost always of one degree and were
      directed towards the 'Negative' class. Conversely, ASCUS was associated with
      considerable proportions of the 'Negative' diagnoses (17.3%) and those of LGSIL
      (31.8%). In the occasions when one observer interpreted a smear as
      'Unsatisfactory' the paired diagnoses were almost evenly distributed among
      'Unsatisfactory' (49.2%) and 'Negative' (43.0%). In absolute terms, the k
      coefficients in this study were compatible with moderate agreement. However, they
      were unfavourably influenced by the modalities for smear selection. The study
      specimens were selected by all cytologists from the routine material over a short
      time period and did not include smears interpretable as showing carcinoma. A
      comprehensive evaluation of the diagnostic performance of C4 showed that the
      disagreement with other cytologists was restricted to the diagnosis of ASCUS and
      the 'Unsatisfactory' notation and was accounted for by a lower frequency of such
      reports coupled with a greater frequency of the 'Negative' diagnoses. A
      conservative approach to lesions of minor significance is the most likely
      explanation for that pattern of disagreement. Although characterized by the
      poorest k value, the ASCUS diagnosis proved to be generally matched with reports
      of minor cytology changes. This was consistent with the formal definition for
      ASCUS in the original Bethesda System. The observation that the ASCUS diagnosis
      is applied to those changes is a prerequisite for a more conservative utilization
      of such report. In conclusion, the study revealed important correlates of the k
      coefficients and provided an encouraging picture of the cytologic substrates of
      the diagnosis of ASCUS.

PMID- 9619056
TI  - [AIDS splenomegaly and related iron problems].
AB  - Spleens collected from 85 consecutive autopsies of AIDS patients (mean age 37
      years) were studied. Splenomegaly, observed in 59 cases (69.4%), does not
      statistically correlate with life style and blood transfusions. Eleven very large
      spleens (over 890 g) were associated with opportunistic infections (i.e.:
      mycobacteria, true fungi and rochalimaea). The histological pattern was
      characterized by marked lymphoid depletion of the white pulp and--in 67 cases
      (89.4%)--packing of the pulp cords by macrophages engulfed of brown pigment which
      was strongly positive to the Perls reaction for ferric iron. The contemporary
      presence of Perls positive and p24 immunoreactive material was diffusely observed
      in the cytoplasm of splenic macrophages, also positive to the alkaline
      tetrazolium reaction. The same was observed in the cytoplasm of
      monocytes/macrophages of lung and brain (in 5 out of 5 patients with splenomegaly
      > 600 g, randomly selected). We believe that our findings deal with the formation
      of a haemoglobin--p24 complex and are in keeping with recent data which suggest
      the formation of disulphide bonds between viral proteins and haemoglobin.

PMID- 9619057
TI  - [Mixed mesodermal tumor of the ovary. Description of a case with a small primary
      neoplastic mass. Anatomo-clinical and histogenetic considerations].
AB  - We describe a rare case of small mixed mesodermal tumor of the ovary (cm 1.5 in
      diameter) with widespread, clinically prevalent, peritoneal metastases. Some
      histological and immunohistochemical findings according with histogenetical
      conversion theory are discussed.

PMID- 9619058
TI  - [Follicular dendritic cell tumor and unusual vascular lesion in lymph node with
      Castleman's disease. Description of a case].
AB  - INTRODUCTION: A case of follicular dendritic cell tumour arising in a lymph-node
      with Castleman's disease, hyaline-vascular type and associated with a vascular
      lesion of the capsule is described. MATERIALS AND METHODS: The lesion is
      documented by immunohistochemistry. RESULTS: The patient is a 57 year old man
      with a large extrathoracic mass showing the combination of the lesions previously
      mentioned. In addition, he was found to have metastatic deposits in a cervical
      lymph-node and in the bone. He underwent radiotherapy and died shortly after with
      post-therapeutical complications. DISCUSSION: The present case constitutes the
      second report of follicular dendritic cell tumour associated with Castleman's
      disease and a benign vascular lesion. This association is discussed.

PMID- 9619059
TI  - [Serous cystadenocarcinoma of the ovary with simultaneous breast metastases.
      Description of a case].
AB  - Metastasis to the breast from extramammary malignancies are rare especially from
      ovarian carcinoma. We report a case of a 72-year-old woman with a mass in the
      right ovary and a lump in the left breast together with axillary lymph node
      enlargement. Both the ovarian and mammary neoplasms were found to be papillary
      carcinoma with similar immunohistochemical pattern (anti-CA-125: positive; anti
      GCDFP-15: negative); some of the axillary lymph nodes showed metastasis with
      papillary features. On the basis of clinical, morphological and
      immunohistochemical data we proposed the diagnosis of papillary
      cystoadenocarcinoma of the ovary with simultaneous metastasis to the breast and
      axillary lymph nodes.

PMID- 9619060
TI  - [Aggressive angiomyxoma in men. Clinicopathological presentation of a new case
      and differential diagnosis considerations].
AB  - A further case of aggressive angiomyxoma in men is reported. This is a rare
      benign locally invasive soft tissue tumor, that should be properly differentiated
      from other benign myxoid tumors, because it needs, for its high tendency to
      recur, a wide-margin surgery. On the other hand, it should be distinguished from
      malignant myxoid tumors, because it lacks metastatic potential and thus any
      adjunctive therapy results useless. With a prevalent incidence in women, we
      retain that it merits a wider recognition also in male urologic pathology.

PMID- 9619062
TI  - [Communication between the pathologist and the clinician: a proposal for
      standardization of the requests for histological examinations for neoplasia].

PMID- 9619061
TI  - [Stromal tumor of the ileum (GIST) at the same time as a renal carcinoma.
      Description of a case and review of the literature].
AB  - The gastrointestinal mesenchymal tumors from a heterogenous group that include
      several entities: leiomyomas, schwanomas and less differentiated tumors often
      referred as GIST. These neoplasm are uncommon and their clinical behaviour is
      most difficult to predict. We describe a malignant gastrointestinal stromal tumor
      of the ileum coexisting with renal cell carcinoma. The neoplasms were fixed in
      formaldehyde, embedded in paraffin and stained with hematoxylin-eosin. For
      immunohistochemical studies deparaffinized tissue sections were incubated with
      antibodies against vimentin, desmin, muscle specific actin, S100, CD34, GFAP, NSE
      and keratin. The epithelioid and spindle cells of ileal neoplasm were arranged in
      interlacing fascicle with occasional palisading and were positive for vimentin
      and CD34. Positivity for muscle specific actin was focally found. The renal
      neoplasm required differential diagnosis from metastatic GIST. The morphological
      and immunohistochemical investigations in our case were consistent with GIST
      coexisting with primitive renal cell carcinoma. One of the problems connected to
      the anatomo-clinical evaluation of GIST consist in the difficulty of making a
      prognosis. An almost complete review of the literature and view point on the
      topic has been performed. As a conclusion judging from papers regarding this
      argument, no clear parameters of biological behaviour exist excluding mitotic
      index.

PMID- 9619063
TI  - [Morphological diagnosis of chronic hepatitis. Minimal requirements for
      histopathological referral].

PMID- 9619064
TI  - Morphometry of melanocytic skin lesions--verifications or vexations? A review of
      a group experience.

PMID- 9619065
TI  - [A courageous genius (a hero, we might say): Rudolf Virchow (1821-1902)].

PMID- 9619066
TI  - [The "vanishing immunohistochemistry" syndrome].

PMID- 9619067
TI  - [Dysplastic nevi].

PMID- 9619068
TI  - [A meeting of Piedmontese anatomo-pathologists].

PMID- 9619069
TI  - [Iodine-123-labeled meta-iodobenzylguanidine myocardial scintigraphy evaluation
      of Machado-Joseph disease].
AB  - Iodine-123-labeled meta-iodobenzylguanidine ([123I]MIBG), an analogue of
      guanetidine, is used as a tracer for evaluation of the function of sympathetic
      neurons. To investigate cardiac sympathetic function in Machado-Joseph disease
      (MJD), [123I] MIBG myocardial scintigraphy was performed in 12 patients with MJD
      and 20 controls. In planar imaging studies, the heart to the mediastinum of the
      average count ratio (H/M) was calculated for both early and delayed images. The
      mean values of H/M in delayed images of MJD was lower than those of controls (p <
      0.01), but this did not correlate with duration of the illness. The mean values
      of H/M in MJD patients with abnormal sympathetic skin response (SSR) was lower
      than that with normal SSR (p < 0.05). The decrease of H/M in delayed image is
      more sensitive than abnormal SSR. The increase of heart rate after standing in
      the patients with low H/M was lower than those with normal H/M. Abnormal cardiac
      sympathetic function revealed by [123I]MIBG myocardial scintigraphy in MJD can be
      seen earlier than abnormal sudomotor system detected by SSR.

PMID- 9619070
TI  - [The significance of hypoplasia of the circle of Willis in patients with
      Binswanger-type cerebrovascular disease].
AB  - We evaluated the correlation between hypoplasia of the circle of Willis detected
      by MR angiography and ischemia of the white matter in patients with Binswanger
      type cerebrovascular disease. We defined P1 hypoplasia as the condition in which
      the posterior cerebral artery at P1 protein was narrower than the posterior
      communicating artery, and A1 hypoplasia as that in which the ratio of the one
      anterior cerebral artery to the other at A1 portion was 1:2 or less. Of 68
      patients with this disease. 33 (48.5%) had P1 hypoplasia and 23 (30.9%) had A1
      hypoplasia. These incidences were significantly higher than those of patients
      with lacunar infarction (138 cases), where P1 and A1 hypoplasia were 29.0% and
      18.1% respectively. P1 hypoplasia tended to be found more frequently in patients
      with lacunar infarction having advanced periventricular hyperintensity than in
      those having mild one. The large intracranial vessels, as seen by MR angiography,
      were less stenotic, and the serum concentration of apolipoprotein A-I was higher
      and B/A-I was lower in hypoplasia cases suffering from Binswanger-type
      cerebrovascular disease than in non-hypoplasia cases. In summary, hypoplasia of
      the circle of Willis was considered to precipitate the onset or progression of
      this disease without any relationship to arteriosclerosis.

PMID- 9619071
TI  - [Hyponatremia in Duchenne muscular dystrophy on mechanical ventilation].
AB  - To evaluate the pathomechanism of hyponatremia occasionally seen in Duchenne
      muscular dystrophy (DMD) on intermittent positive pressure ventilation (IPPV), we
      performed a comparative study on 26 DMD patients, 7 IPPV in trachetomized
      intermittent positive pressure ventilation (TIPPV), 6 nasal intermittent positive
      pressure ventilation (NIPPV), 6 cuirass respirator (CR), and 7 spontaneous
      breathings (SB). We followed fluctuation of serum sodium levels for several
      years. Since the serum sodium level was gradually reduced with years on
      mechanical ventilation, we speculated positive relationship between hyponatremia
      and antidiuretic hormone (ADH) secretion. Serum sodium levels of 135.6 +/- 2.8
      mEq/L in average on IPPV (TIPPV + NIPPV) patients was significantly lower than
      the levels of 137.8 mEq/L +/- 0.98 on CR patients and 138.8 +/- 0.69 mEq/L on SB
      patients. Plasma ADH levels in IPPV patients were not reduced when plasma
      osmolarity was less than 280 mOSm/L. Previous reports showed that ADH was
      inappropriately secreted only during IPPV with positive end expiratory pressure
      (PEEP). Ours is the first report of inappropriate secretion of ADH during IPPV
      without PEEP. It becomes clear that inappropriate ADH secretion is one of the
      causes of hyponatremia in DMD, though the exact mechanism is not clear. We should
      bear in mind the change of serum electrolyte level in ventilated DMD patients,
      especially patients on antidepressant known to release of ADH.

PMID- 9619072
TI  - [A case of dural arteriovenous malformation associated with progressive dementia
      showing marked improvement with endovascular treatment].
AB  - An 81-year-old man was admitted with a 3-month history of progressive dementia.
      Neurological examination revealed marked dementia, parkinsonism and myoclonus in
      his extremities. His cerebrospinal fluid examination was normal. An
      electroencephalogram showed a mildly slowed background. Computed tomography (CT)
      disclosed diffuse low-density areas in bilateral cerebral white matter. Contrast
      enhanced CT demonstrated vermiform enhancement of engorged cortical veins,
      suggesting increased pressure of the venous system. Magnetic resonance imaging
      (MRI) disclosed diffuse high-intensity areas in bilateral cerebral white manner
      on T2-weighted images, and abnormal flow-voids presenting venous congestion on
      proton-density images. Cerebral angiography revealed arteriovenous malformation
      (AVM) fed by four branches of the right external carotid artery with retrograde
      drainage into the right transverse sinus, superior sagittal sinus, and dilated
      cortical veins. The ipsilateral sigmoid sinus was not visualized. After
      transarterial embolization, transvenous embolization of the right transverse
      sinus was performed. These treatments resulted in a marked clinical improvement.
      We emphasize the role of AVM as a cause of progressive dementia.

PMID- 9619073
TI  - [A case of chronic inflammatory demyelinating polyradiculoneuropathy complicated
      by phrenic nerve palsy].
AB  - We report on a patient with chronic inflammatory demyelinating
      polyradiculoneuropathy (CIDP) complicated by phrenic nerve palsy. A 50-year-old
      man was admitted to our hospital due to dyspnea and numbness in his limbs. On
      admission, severe muscle atrophy, weakness, and sensory disturbance were seen in
      the distal part of his extremities. Deep tendon reflexes were absent in all the
      limbs. Routine blood examinations showed no abnormal findings except for mild
      hyperglycemia (fasting blood sugar 145 mg/dl). Right phrenic nerve palsy was
      observed on a chest roentgenogram and % vital capacity (%VC) was 56%.
      Cerebrospinal fluid showed elevated levels of total protein (116 mg/dl) and IgG
      (16.9 mg/dl). Sural nerve biopsy revealed severe loss of myelinated fibers with
      demyelination and onion-bulb formation. After immunoadsorption plasmapheresis,
      the phrenic nerve palsy improved rapidly and %VC recovered to 76%. Although
      phrenic nerve palsy is rare in patients with CIDP, it is important to take notice
      of this condition, because phrenic nerve palsy is critical when it occurs
      bilaterally or when it develops in patients who have suffered from respiratory
      diseases. Immunoadsorption plasmapheresis is one of the effective treatments for
      CIDP, especially in patients with serious complications such as phrenic nerve
      palsy.

PMID- 9619074
TI  - [Panhypopituitarism following basilar artery dissection with extensive brainstem
      and cerebellar infarction: a case report].
AB  - We experienced a patient with panhypopituitarism which occurred following
      extensive brainstem and cerebellar infarction due to dissection of basilar artery
      (BAD). Panhypopituitarism followed by BAD has not yet been reported in the
      literature. The patient was a 67-years-old man who was admitted to our hospital
      because of a sudden onset of consciousness disturbance and vomiting. On the day
      of admission, he was drowsy and had left IIIrd nerve palsy, skew deviation,
      occular bobbing, and left hemiparesis. His neurological state was rapidly
      deteriorated, and fell almost into apneic state, requiring artificial ventilation
      for a week. Cerebral angiography demonstrated a double lumen sign of the basilar
      artery confirming the diagnosis of dissection. There were extensive hypodensities
      in the brainstem and bilateral cerebellar hemispheres on CT. On day 20, he
      suddenly became shocked following infection. Even after the effective and
      successful treatment of infection, severe hypotension continued that required
      administration of chatecholamine agents. Laboratory examinations revealed that he
      had panhypopituitarism. Supplement therapy with adrenocortical hormones made his
      circulatory state improved, and could finally be stopped on day 100. In the
      present case, subclinical hypopituitarism was considered to occur mainly from
      compression of the pituitary stalk and hypothalamus by the enlarged BAD.
      Increased intracranial pressure and upward herniation may also have made the
      pituitary function worse, and the infection finally triggered the adrenal crisis.
      The BAD occurs more frequently than previously considered, and should be kept in
      mind as a cause of secondary panhypopituitarism.

PMID- 9619075
TI  - [An autopsy case of rigid spine syndrome].
AB  - We reported an autopsy case of rigid spine syndrome. A 20-year-old woman
      developed severe respiratory failure despite well-preserved muscle strength in
      her extremities. Although she had mechanical ventilation during sleep, she had
      normal arterial blood gas values during daytime. She was found dead in a morning
      approximately 71/2 years after the onset of the respiratory symptoms. At autopsy,
      the respiratory diaphragm and intercostal muscles, and the truncal paravertebral
      and sternocleidomastoid muscles were more significantly affected than the limb
      muscles. Many corpora amylacea were found in the whole spinal cord, though the
      significance remains to be elucidated.

PMID- 9619076
TI  - [A case of dural arteriovenous fistula accompanied by sinus occlusion. A serial
      study with CT scan].
AB  - A dural arteriovenous fistula (AVF) of the posterior fossa was found in a 58-year
      old businessman suffering from a month's history of dementia. Bilateral
      transverse sinus thrombosis was also found and his symptom was attributed to
      venous congestion caused by the sinus occlusion. He had received partial
      resection of the right trigeminal neurinoma two years before, and the operation
      was thought to have caused the sinus occlusion. Dural AVF of the posterior fossa
      usually causes tinnitus or headache, whereas dementia seen in present case is
      relatively rare. In the present case, serial study of cranial CT scan
      demonstrated evolution of dural AVF after sinus occlusion. Venous congestion was
      thought to re-open the physiological micro-AVF to cause the dural AVF.

PMID- 9619077
TI  - [Cerebral embolism with hemiballism due to putaminal lesion].
AB  - A 66-year-old man was admitted to our hospital because of hemiballism of his left
      extremities. The hemiballism disappeared soon after beginning therapy with
      haloperidol and chlorpromazine. X-ray CT brain scan on day 3 showed infarction in
      the right putamen and the right parietal lobe. Cerebral angiography on day 9 was
      normal. Transesophageal echocardiography revealed no abnormality except for an
      atrial septal aneurysm. Transcranial color-flow imaging demonstrated high
      intensity transient signal (HITS) with Valsalva maneuver. Paradoxical embolism
      was, therefore, thought to have caused the patient's brain infarction. It was
      speculated that the hemiballism was caused by disinhibition of the cortex
      resulting from loss of negative feedback in the motor system due to the putaminal
      lesion. It is necessary to treat hemiballism using an appropriate therapy to
      prevent exacerbation.

PMID- 9619078
TI  - [A case of livedo vasculitis associated with mononeuritis multiplex].
AB  - Livedo vasculitis is characterized by recurrent livedo reticularis of lower
      extremities and the histopathological findings of segmental hyalinizing
      vasculitis in the skin. We report a case of a 26-year-old female who manifested
      mononeuritis multiplex 7 years after the onset of livedo vasculitis. She showed
      sensori-motor disturbances in the right median and ulnar nerves and sensory
      deficits of the bilateral peroneal nerves. Sural nerve biopsy revealed a
      remarkable loss of large and small myelinated fibers and a few vasculitic
      changes. Steroids therapy was effective for these neurological symptoms. But
      paroxysmal numbness appeared later recurrently in the regions of affected nerves
      with painful ulcerations in the right leg. Laboratory tests indicated increased
      levels of serum thrombin-antithrombin complex (TAT), and antithrombotic drugs
      (argatroban) remarkably ameliorated the recurrent symptoms and skin lesions.
      These findings suggest that the pathogenesis of livedo vasculitis might be
      related to alterations of the blood coagulation system.

PMID- 9619079
TI  - [A case presenting progressive hand clumsiness and discriminative sensory
      impairment].
AB  - A 58-year-old right-handed woman had presented slowly progressive clumsiness of
      the right hand over the past 8 years. The clumsiness of the right hand was
      characterized by difficulty in using scissors and a comb or in imitating finger
      patterns that resembled to limb kinetic apraxia. Mild rigidity, weakness and
      synkinetic movement were noted in the right upper extremity. Two-point
      discrimination, traced-figure identification and stereognosia were impaired on
      the right hand. However, she was neither demented nor aphasic. Brain MRIs
      revealed atrophy of the pre- and post-central gyri with marked preponderance on
      the left postcentral gyrus. 99mTc-ECD-SPECT uptake was decreased in the above
      brain atrophy areas. Upper limb SEPs were normal, but transcranial magnetic
      stimulation over the cortical hand motor area failed to evoke potentials from the
      right thenar muscles. These unique features seem to reflect focal cerebral
      degenerative process of unknown etiology, which may be classified into an
      asymmetric cortical degeneration syndrome (Caselli and Jack, 1992).

PMID- 9619080
TI  - [A case of brain stem encephalitis with bilateral horizontal gaze palsy].
AB  - A 41-year-old woman developed horizontal diplopia and difficulty in moving her
      eyes. On neurological examination, her eyes showed absolute bilateral horizontal
      gaze palsy, but convergency and vertical eye movement were normal. The
      cerebrospinal fluid findings revealed an increased IgG level and myelin basic
      protein. T2-weighted magnetic resonance imaging revealed a high-signal-intensity
      area in the lower pontine tegmentum affecting bilateral horizontal gaze. We
      diagnosed her as having brain stem encephalitis based on the above data. After
      1.5 months of corticosteroid treatment, bilateral horizontal palsy disappeared
      completely. Several cases showing bilateral horizontal gaze palsy have been
      reported, but few have involved absolute bilateral horizontal gaze palsy caused
      by brain stem encephalitis.

PMID- 9619081
TI  - [Pure alexia due to a fusiform gyrus lesion].
AB  - We present a patient with pure alexia following a hemorrhagic infarction in the
      left fusiform gyrus. The symptom began with alexia preferentially disturbed for
      kana, but during the course of recovery slight agraphia for kanji became
      pronounced. In the earlier phase, alexia was more severe than agraphia and he
      could write kanji that he could not read. Furthermore, kinesthetic reading was
      effective. These findings are consistent with the symptoms of pure alexia,
      although the fact that a writing disturbance for kanji persisted resembles the
      profile of alexia with agraphia for kanji due to a posterior inferior temporal
      lesion. Based on the fact that the posterior inferior temporal lesion showed more
      severe agraphic symptom and more frequent nonresponse writing errors of kanji,
      and that our patient's lesion was mainly located in the fusiform gyrus that is
      medial to the inferior temporal gyrus, we believe that alexia occurred when the
      inferior temporal gyrus was disconnected from the fusiform gyrus, as a result,
      visual information could not reach the inferior temporal gyrus in which the
      visual images of individual kanji are stored.

PMID- 9619082
TI  - [Features of MRI diffusion weighted image in early stage of lateral medullary
      infarction presenting Wallenberg syndrome].
AB  - We described early features of MRI diffusion weighted images (DWIs) in three
      patients with lateral medullary infarction. Patient 1. A 65-year-old woman who
      complained of vertigo was admitted. Then, DWIs showed a high signal intensity in
      the right lateral medulla, though T2 weighted images (T2WIs) did not show any
      abnormalities. On the next day, when the typical symptoms and signs of lateral
      medullary infarction appeared, the lesion was recognized on both DWIs and T2WIs.
      Patient 2. A 48-year-old man was admitted 9 hours after he had dizziness, nausea,
      and repeated vomitings. When a diagnosis of Wallenberg syndrome was made on the
      neurological examination, MRI DWIs demonstrated a high signal intensity in the
      right lateral medulla. The lesion became apparent on T2WIs 82 hours after the
      onset. Patient 3. A 71-year-old man was admitted for nausea, dizziness, and
      repeated vomitings. A diagnosis of Wallenberg syndrome was made fifty eight hours
      after the onset, a lesion with high signal intensity in the right lateral medulla
      was evident on DWIs, but it was faint on T2WIs. We concluded that DWIs is useful
      in early diagnosis of lateral medullary infarction presenting Wallenberg
      syndrome.

PMID- 9619083
TI  - [Prognosis in the Reye's syndrome].

PMID- 9619084
TI  - Progress towards leprosy elimination.

PMID- 9619085
TI  - The 50th anniversary of WHO.

PMID- 9619086
TI  - El Nino and its health impacts.

PMID- 9619087
TI  - The Faculty of Medical Sciences at 50.

PMID- 9619088
TI  - The Faculty of Medical Sciences--notes of a personal odyssey.

PMID- 9619089
TI  - Autism in Jamaica.
AB  - This paper reviews childhood autism, a serious psychopathological disorder, with
      emphasis placed on aetiology and management; and outlines briefly the care of the
      autistic population in a few well organized programmes existing in Jamaica. There
      is a need for increased awareness, local research and dissemination of
      information to appropriate personnel and organizations.

PMID- 9619090
TI  - Surveillance of leptospiral carriage by feral rats in Barbados.
AB  - Rodents, particularly rats, are widely held to be the source of most human cases
      of leptospirosis. Feral rats were trapped at sites throughout Barbados during two
      six month surveys: from October to March 1986/87 and from October to March
      1994/95. During the first survey, 63 rats were trapped, of which 26 (41%) were
      identified as Rattus rattus and 37 (59%) as Rattus norvegicus. In the second
      study, 100 rats were trapped, of which R. rattus comprised 24% (24) and R.
      norvegicus 76% (76). Cultures of blood, urine and kidney were made in EMJH
      medium. Leptospires were isolated from 12/63 (19%) and from 16/100 (16%) of the
      rats during 1986/87 and 1994/95, respectively; 27/28 isolates were recovered from
      the kidneys or urine or both, while only one isolate was recovered from the
      blood. During the first study, isolates were identified as serovars copenhageni
      (11) and arborea (1), while in the second study, serovars copenhageni (9),
      arborea (5) and bim (1) were identified; one isolate was lost before it could be
      identified. In the first study, antibodies were detected by microscopic
      agglutination at a titre of > or = 100 in 26/62 (42%) of rats tested, while in
      the second survey, 5/100 (5%) of rats had similar titres. In two surveys,
      conducted eight years apart, we confirmed that rats in Barbados are commonly
      infected with leptospires, and that viable organisms are found in the kidneys and
      urine, evidence of chronic infection and thus excretion of leptospires in rodent
      urine. Moreover, the predominant serovar isolated was copenhageni, of which
      Rattus spp. are the worldwide reservoir. There was little evidence that rats act
      as a reservoir for the serovar bim, the most common cause of human leptospirosis
      in Barbados.

PMID- 9619091
TI  - Neurological and neurosurgical referrals overseas from the Queen Elizabeth
      Hospital, Barbados, 1987-1996.
AB  - This paper reports on neurological and neurosurgical referrals overseas from the
      Queen Elizabeth Hospital (QEH) for the period November 1987 to November 1996, and
      is a follow up to an earlier report for the period January 1984 to November 1987.
      It outlines the pattern of referral, diagnoses, referral centres and costs based
      on examination of the files of all QEH patients transferred overseas under a
      government aided scheme. There were 203 transfers of 191 patients (69 males, 122
      females) including 10 patients who were transferred twice and one patient who was
      transferred three times. Patients' ages ranged from 1 to 80 years (mean 37
      years). Twenty overseas centres were used during the period but most patients
      were transferred to Brooklyn Hospital, New York in 1988, Mount Sinai Medical
      Center, New York, between 1989 and 1994, and Hospital de Clinicas Caracas,
      Venezuela (1992 to 1996). 65% of the referrals were for neurosurgery and 25% were
      for magnetic resonance imaging scans for diagnosis. The largest diagnostic
      categories were central nervous system tumors (40%) and subarachnoid haemorrhage
      (25%). Estimated costs reached almost BDS$11 million, but the mean actual cost
      was BDS$63,916 based on information from 123 patient transfers. Thus, the actual
      total government expenditure was probably closer to BDS$13 million. This study
      demonstrates the urgent need to establish a neurosurgical service at the QEH and
      the cost effectiveness of doing so.

PMID- 9619092
TI  - Prevalence of viral and bacterial sexually transmitted pathogens in Jamaican
      pregnant women.
AB  - In this study we investigated the prevalence of Chlamydia trachomatis, Neisseria
      gonorrhoeae, Treponema pallidum, human immunodeficiency virus type I (HIV-I),
      human T cell lymphotropic virus type 1 (HTLV-1) and hepatitis B virus (HBV)
      infections in 200 pregnant women attending antenatal clinics at the University
      Hospital of the West Indies. 19% of the women had at least one pathogen: C.
      trachomatis was found in 16%, HTLV-1 in 2%, HIV-1, HBV and N. gonorrhoeae each in
      0.5% C. trachomatis infection was more prevalent in women less than 20 years of
      age (31%) than in those 20 years and older (16%; OR = 0.43; chi 2 = 5.66; p <
      0.05). The study demonstrates the need for identification of sexually transmitted
      pathogens in antenatal women for syndromic management of genital infections as
      part of the strategy for prevention and control of HIV/AIDS (acquired
      immunodeficiency syndrome) in Jamaica.

PMID- 9619093
TI  - Percutaneous balloon mitral valvuloplasty for severe rheumatic mitral stenosis in
      Jamaica: the initial experience.
AB  - Although percutaneous balloon mitral valvuloplasty has been performed in the
      Caribbean before, there has not been any detailed description in the English
      speaking West Indian Medical literature hitherto. This report provides a
      description of the first four cases of percutaneous balloon mitral valvuloplasty
      performed in Jamaica.

PMID- 9619094
TI  - Hydrostatic reduction of acute intussusception. A prospective study.
AB  - Data were collected prospectively on 57 Jamaican children presenting with 62
      episodes of acute intussusception over a two year period, for whom operative and
      hydrostatic methods of reduction were employed. 31 (54%) of 57 episodes were
      reduced successfully using barium (42), saline (11) and air (4) hydrostatically.
      Among the 31 other episodes, 15 had ileo-colic intussusception, seven caeco
      colic, six ileo-ileo-colic and one ileo-ileal. Two patients had spontaneous
      reduction discovered at surgery. There were two episodes of barium hydrostatic
      perforation of the colon leading to death in one patient. Hydrostatic reduction
      is recommended as the first therapeutic option for acute intussusception because
      it spares the patient a major operative procedure when successful.

PMID- 9619095
TI  - Cancrum oris (noma) in a patient with acute lymphoblastic leukaemia. A
      complication of chemotherapy induced neutropenia.
AB  - Cancrum oris (noma) has been most commonly described in malnourished debilitated
      children with poor oral hygiene following systemic childhood infections such as
      measles, pertussis or scarlet fever. We describe a patient who developed this
      condition during a period of profound neutropenia following cytotoxic
      chemotherapy for acute lymphoblastic leukaemia.

PMID- 9619096
TI  - Angiomyofibroblastoma--a rare but distinct entity.
AB  - A case of angiomyofibroblastoma of the vulva in a 23-year-old woman is presented.
      Clinical, histological and immunohistochemical features as well as the
      differential diagnosis and prognosis of this rare but distinct entity are
      discussed. Only about 65 cases are documented in the literature and to our
      knowledge this is the first case to be reported from the Caribbean.

PMID- 9619097
TI  - Bookmarking genes for activation in condensed mitotic chromosomes.
AB  - A hallmark feature of mitosis is the extinction of bulk cellular transcription.
      The mechanism by which transcription is abrogated is likely linked to mitotic
      specific events such as chromosome condensation. Recent studies that probe the
      structure of genes that can be reactivated rapidly after mitotic repression
      (early G1) suggest that there are structural distortions in the promoter regions
      of these genes. These distortions are absent in genes that are typically
      repressed or reactivated in later phases of the cell cycle (late G1, S, or G2).
      Such changes in the chromatin structure of these genes may create a transient
      window for transcription factor binding and rapid reactivation of genes in
      subsequent phases of the cell cycle.

PMID- 9619098
TI  - Plant homeobox genes: many functions stem from a common motif.
AB  - Homeodomain-containing transcription factors play a variety of important roles in
      plant, animal, and fungal development. Mutational and evolutionary analysis is
      beginning to pinpoint specific roles of homeobox genes in plant meristem
      function. Even though many different plant homeobox genes encode very similar
      homeodomain sequences, overexpression studies suggest the existence of several
      levels of regulation that may specify the functions of the different proteins.
      Recent analysis of the maize Knotted1 gene and its orthologue in barley
      demonstrates some of these regulatory processes.

PMID- 9619099
TI  - Uncoupling growth from the cell cycle.
AB  - How does a Drosophila wing grow to the appropriate size and shape? Although a
      collaboration of cell division with the patterning of cell fates seems obvious,
      almost nothing is known about how these two processes are coordinated during
      development. A recent paper finds that blocking cell division uncouples cell
      growth from the cell division cycle, displaying remarkable flexibility in the
      ability of the wing primordia to achieve the right proportions with fewer than
      normal cells.

PMID- 9619100
TI  - Alternative repair pathways for UV-induced DNA damage.
AB  - Ultraviolet light (UV) is thought to have had a major impact on the early
      evolution of life. UV is absorbed by nucleic acids and produces several types of
      DNA damage, which interfere with DNA replication and transcription. This damage
      can result in mutagenesis and cell killing. Several mechanisms for repairing UV
      induced DNA damage have been identified. Besides the widely distributed
      nucleotide excision repair, two alternative repair mechanisms for specific
      lesions in UV-damaged DNA are known, involving photolyases and DNA glycosylases.
      Recently, a novel endonuclease for UV-induced DNA damage was identified that
      initiates an excision repair pathway completely different from previously
      established repair mechanisms. The finding of this "alternative excision repair"
      suggests the presence of a new category of DNA repair, initiated by single-strand
      breaks in DNA. Homologues of the UVDE enzyme have been found in eukaryotic
      microorganisms, as well as in bacteria, indicating that the enzyme originated
      early in evolution, and suggesting the existence of multirepair systems for UV
      induced DNA damage during early evolution.

PMID- 9619101
TI  - The function of hairy-related bHLH repressor proteins in cell fate decisions.
AB  - Hairy-related proteins are a distinct subfamily of basic helix-loop-helix (bHLH)
      proteins that generally function as DNA-binding transcriptional repressors. These
      proteins act in opposition to bHLH transcriptional activator proteins such as the
      proneural and myogenic proteins; together, the activator and repressor genes that
      encode these proteins have co-evolved as a regulatory gene "cassette" or "module"
      for controlling cell fate decisions. In the development of the Drosophila
      peripheral nervous system, Hairy-related genes function at multiple steps during
      neurogenesis, for example, as positional information genes that establish the
      "prepattern" that controls where "proneural cluster" equivalence groups will
      form, and later as nuclear effectors of the Notch signaling pathway to "single
      out" individual precursor cells within the equivalence group. Hairy-related genes
      also function in the establishment and restriction of other types of equivalence
      groups, such as those for muscle and Malphigian tubule precursors. This general
      function in cell fate specification has been conserved from Drosophila to
      vertebrates and has implications for human disease pathogenesis.

PMID- 9619102
TI  - Placental endogenous retrovirus (ERV): structural, functional, and evolutionary
      significance.
AB  - That endogenous retrovirus (ERV) is present within the placenta of humans and
      other mammals has been known for the past 25 years, but the significance of this
      observation is still not fully understood. Much molecular biological data have
      emerged in recent years to support the earlier electron microscopic data on the
      presence of placental ERV. The evidence for ERV in animal and human placental
      tissue is presented, then integrated with data on the presence of ERV in a range
      of other tissues, in particular teratocarcinoma cells. Placental invasiveness and
      maternal immunosuppression are then discussed in relation to metalloproteinase
      secretion, the immunosuppressive potential of retroviruses, and placental growth
      factors, while the evidence for a functional link between placental
      protooncogenes and trophoblast malignancy is reviewed. Finally, placental
      development, structure, and life span are discussed within an evolutionary
      context. The hypothesis that one or more ancient trophoblastic ERVs could have
      played a role in the evolution and divergence of all placental mammals is
      evaluated.

PMID- 9619103
TI  - In vivo gap repair in Drosophila: a one-way street with many destinations.
AB  - While it has long been possible to study the process of recombination in yeast
      and other single-celled organisms, it has been difficult to distinguish between
      pathways of meiotic and mitotic recombination in multicellular eukaryotes. The
      experimental system described here bridges the historically separated fields of
      Genetic Recombination and DNA Repair in Drosophila. It is now feasible to study
      the repair of unique double-strand breaks induced in the Drosophila genome by the
      excision of a P-transposable element or by cleavage at an introduced endonuclease
      recognition sequence. This repair can be studied in both somatic cells and
      mitotically dividing germ cells. The repair of these breaks occurs mainly by
      copying sequence from a template located anywhere in the karyoplasm, and occurs
      in both male and female flies. This system, which was the first of its kind in
      metazoan organisms, is now being used for gene targeting in Drosophila. This
      review summarizes results that provide new insights into the process of gap
      repair in Drosophila and outline some recent experiments that demonstrate the
      power of the gene targeting technique.

PMID- 9619104
TI  - Analysis of regulated exocytosis in adrenal chromaffin cells: insights into
      NSF/SNAP/SNARE function.
AB  - Many of the proteins that function in regulated exocytosis have now been
      identified. Several proteins form part of a conserved core machinery that acts in
      many intracellular vesicular fusion steps and their essential roles confirmed by
      molecular genetic analysis. In addition, studies with adrenal chromaffin and PC12
      cells have demonstrated the function of various proteins in regulated exocytosis
      and have permitted dissection of the stages of exocytosis in which they act. N
      Ethylmaleimide-sensitive fusion protein (NSF) and soluble NSF attachment proteins
      (SNAPs) are key proteins in exocytosis. Examination of their function has
      indicated that they have a predocking role most likely as molecular chaperones to
      prepare the docking/fusion machinery. The exact site and time of action in
      exocytosis of many of the other identified proteins are unknown. A major emphasis
      for the future will be analysis of the molecular physiology of regulated
      exocytosis to permit the assignment of functions to identified proteins in
      particular stages of the regulated exocytotic pathway.

PMID- 9619105
TI  - Host-microbial symbiosis in the mammalian intestine: exploring an internal
      ecosystem.
AB  - The mammalian intestine contains a complex, dynamic, and spatially diversified
      society of nonpathogenic bacteria. Very little is known about the factors that
      help establish host-microbial symbiosis in this open ecosystem. By introducing
      single genetically manipulatable components of the microflora into germfree mice,
      simplified model systems have been created that will allow conversations between
      host and microbe to be heard and understood. Other paradigms of host-microbial
      symbiosis suggest that these interactions will involve an exchange of biochemical
      signals between host and symbionts as well as among the bacteria themselves. The
      integration of molecular microbiology, cell biology, and gnotobiology should
      provide new insights about how we adapt to a microbial world and reveal the roles
      played by our indigenous, 'nonpathogenic' flora.

PMID- 9619106
TI  - More on scientific reasoning.

PMID- 9619107
TI  - Solubilized hypericin and pseudohypericin from Hypericum perforatum exert
      antidepressant activity in the forced swimming test.
AB  - It has been shown recently that the fraction IIIc of a crude extract of Hypericum
      perforatum, (St. John's wort) that contained both hypericin (1) and
      pseudohypericin (2), was remarkably active in the rats forced swimming test (FST)
      after Porsolt. However, neither of the naphthodianthrones isolated from this
      fraction were sufficiently effective when administered suspended in water. The
      solubility of 1 and 2 is remarkably increased in the presence of a fraction
      containing procyanidins, especially procyanidin B2, which is present also in the
      active Hypericum fraction IIIc. The cooperative effect of procyanidins
      significantly increased the in vivo effects of 1 and 2, which exhibited inverted
      U-shaped dose response curves, in the FST. The anti-immobility effect of
      solubilized 1 and 2 was antagonized by the dopamine antagonist sulpiride. These
      data indicate that naphthodianthrones are antidepressant constituents of H.
      perforatum and suggest that the dopaminergic system is involved in their action.

PMID- 9619108
TI  - Biologically active substances from the genus Artemisia.
AB  - Artemisia species, widespread in nature, are frequently utilized for the
      treatment of diseases such as malaria, hepatitis, cancer, inflammation, and
      infections by fungi, bacteria, and viruses. Furthermore, some Artemisia
      constituents were found to be potential insecticides and allelopathic chemicals.
      This genus is receiving growing attention presumably due to: (i) the diversified
      biology and chemistry of the constituents, (ii) the frequent application in
      traditional medical practice, and (iii) the rich source of the plant material.
      This review summarizes mainly the biological results obtained in the past decade.
      The significance and trends in this field are briefly discussed.

PMID- 9619109
TI  - Natural inhibitors for protein prenyltransferase.
AB  - Farnesyl protein transferase (FPT) catalyzes the posttranslational farnesylation
      of the cysteine residue located in the carboxyl-terminal tetrapeptide of the Ras
      oncoprotein. Prenylation of this residue is essential for membrane association
      and cell transforming activities of Ras. Inhibitors of FPT have been demonstrated
      to inhibit Ras-dependent cell transformation and thus represent a potential
      therapeutic strategy for the treatment of human cancers (1). In the present
      study, the inhibitory principles for protein prenyltransferases were isolated and
      identified from Ganoderma lucidum and garlic. The inhibitors from Ganoderma
      lucidum were identified as ganoderic acid A and ganoderic acid C by comparison
      with the reported spectral data. Ganoderic acid A has an IC50 value of 100 microM
      against FPT and its methyl ester (methyl ganoderate A) has an IC50 value of 38
      microM for the same enzyme. These inhibitors appear to be competitive with
      farnesyl pyrophosphate (FPP), and Ki values of ganoderic acid A and methyl
      ganoderate A are 54 microM and 20 microM, respectively. The inhibitors from
      garlic were identified as diallyl thiosulfinate (allicin), methyl allyl
      thiosulfinate, and allyl methyl thiosulfinate. These inhibitors are more
      effective against geranylgeranyl protein transferase (GGPT) than FPT and IC50
      values of allicin, methyl allyl thiosulfinate, and allyl methyl thiosulfinate for
      GGPT were 43 microM, 57 microM, and 53 microM, respectively. Methyl allyl
      thiosulfinate appears to be competitive with geranylgeranyl pyrophosphate (GGPP)
      and its Ki was determined to be 15 microM. The molecular structures of
      triterpenes and thiosulfinates are expected to be useful in designing lead
      compounds for new potent antitumour agents.

PMID- 9619110
TI  - Galphimine-B modifies electrical activity of ventral tegmental area neurons in
      rats.
AB  - Galphimine-B (G-B) is a bioactive compound isolated from the plant Galphimia
      glauca Cav. (Malpighiaceae) with central nervous system depressant properties
      previously described. In the present study, extracellular spiking activity
      records in either somatosensorial cortex or ventral tegmental area (VTA) neurons,
      were performed in rats after i.p. or local administration of G-B. None of the
      cortical neurons displayed significant changes induced by any of the applied
      doses. In VTA cells, two patterns of electrical discharge were recorded, bursting
      (57%) and nonbursting (43%) types. Systemic administration of G-B induced
      excitatory effects in neurons with a bursting firing pattern and mixed responses
      on nonbursting units. When this compound was applied locally by
      microiontophoresis, most of the bursting and nonbursting spiking neurons showed a
      firing depression and only a few of the nonbursting neurons showed an increment
      of discharge frequency. These results are important since VTA is a major
      dopaminergic center responsible for the innervation of the prefrontal cortex,
      nucleus accumbens and entorhinal region. These areas are targets for the action
      of antipsychotic drugs.

PMID- 9619111
TI  - Extract of corn silk (stigma of Zea mays) inhibits the tumour necrosis factor
      alpha- and bacterial lipopolysaccharide-induced cell adhesion and ICAM-1
      expression.
AB  - Treatment of human endothelial cells with cytokines such as tumour necrosis
      factor-alpha (TNF) or E. coli lipopolysaccharide (LPS) induces the expression of
      several adhesion molecules and enhances leukocyte adhesion to endothelial cell
      surface. Interfering with this leukocyte adhesion or adhesion molecules
      upregulation is an important therapeutic target for the treatment of bacterial
      sepsis and various inflammatory diseases. In the course of screening marketed
      European anti-inflammatory herbal drugs for TNF antagonistic activity, a crude
      ethanolic extract of corn silk (stigma of Zea mays) exhibited significant
      activity. The extract at concentrations of 9-250 micrograms/ml effectively
      inhibited the TNF- and LPS-induced adhesiveness of EAhy 926 endothelial cells to
      monocytic U937 cells. Similar concentration ranges of corn silk extract did also
      block the TNF and LPS but not the phorbol 12-myristate 13-acetate-induced ICAM-1
      expression on EAhy 926 endothelial cell surface. The extract did not alter the
      production of TNF by LPS-activated macrophages and failed to inhibit the
      cytotoxic activity of TNF. It is concluded that corn silk possesses important
      therapeutic potential for TNF- and LPS-mediated leukocyte adhesion and
      trafficking.

PMID- 9619112
TI  - Niaziminin, a thiocarbamate from the leaves of Moringa oleifera, holds a strict
      structural requirement for inhibition of tumor-promoter-induced Epstein-Barr
      virus activation.
AB  - Three known thiocarbamate (TC)- and isothiocyanate (ITC)-related compounds have
      been isolated from the leaves of Moringa oleifera, a traditional herb in
      southeast Asia, as inhibitors of tumor promoter teleocidin B-4-induced Epstein
      Barr virus (EBV) activation in Raji cells. Interestingly, only niaziminin among
      10 TCs including 8 synthetic ones showed considerable inhibition against EBV
      activation. The structure-activity relationships indicated that the presence of
      an acetoxy group at the 4'-position of niaziminin is important and indispensable
      for inhibition. On the other hand, among the ITC-related compounds, naturally
      occurring 4-[(4'-O-acetyl-alpha-L-rhamnosyloxy)benzyl]ITC and commercially
      available allyl- and benzyl-ITC significantly inhibited activation, suggesting
      that the isothiocyano group is a critical structural factor for activity.

PMID- 9619113
TI  - Proanthocyanidins from the bark of Hamamelis virginiana exhibit antimutagenic
      properties against nitroaromatic compounds.
AB  - The antimutagenic activity of Hamamelis virginiana bark was examined in the Ames
      assay. A commercial tincture and a methanolic extract showed dose-dependent
      inhibitory effects on mutagenicity induced by 2-nitrofluorene. Tannin-free
      samples did not display any inhibition. Bioassay-guided fractionation resulted in
      the isolation of two active fractions which were shown to contain oligomeric,
      proanthocyanidins. They were capable of inhibiting the mutagenicity of selected
      nitroaromatic compounds. The mechanism of antimutagenic action was also studied.
      The proanthocyanidins did not act as bioantimutagens, but rather as direct-acting
      desmutagens. The antimutagenic effect increased with an increasing degree of
      polymerisation in the proanthocyanidins. The most active fraction consisted of
      catechin and gallocatechin oligomers with an average polymerisation degree of
      9.2.

PMID- 9619114
TI  - Inhibitory activity of boswellic acids from Boswellia serrata against human
      leukemia HL-60 cells in culture.
AB  - Four major triterpene acids including beta-boswellic acid (1), 3-O-acetyl-beta
      boswellic acid (2), 11-keto-beta-boswellic acid (3), and 3-O-acetyl-11-keto-beta
      boswellic acid (4) were isolated from the gum resin of Boswellia serrata and
      examined for their in vitro antitumor activity. They inhibited the synthesis of
      DNA, RNA and protein in human leukemia HL-60 cells in a dose dependent manner
      with IC50 values ranging from 0.6 to 7.1 microM. Among them, compound 4 induced
      the most pronounced inhibitory effects on DNA, RNA and protein synthesis with
      IC50 values of 0.6, 0.5, and 4.1 microM, respectively. The effect of 4 on DNA
      synthesis was found to be irreversible. Compound 4 significantly inhibited the
      cellular growth of HL-60 cells, but did not affect cell viability.

PMID- 9619115
TI  - Torilin, a sesquiterpene from Torilis japonica, reverses multidrug-resistance in
      cancer cells.
AB  - A sesquiterpene compound reversing multidrug-resistance in cancer cells was
      isolated from the fruits of Torilis japonica and the structure was identified as
      torilin. Torilin potentiated the cytotoxicities of adriamycin, vinblastine, taxol
      and colchicine against multidrug-resistant KB-V1 and MCF7/ADR cells.

PMID- 9619116
TI  - Mode of action of torilin in multidrug-resistant cancer cell lines.
AB  - The mechanism of action of multidrug-resistance reversing activity of torilin was
      studied. In vitro experiments for the accumulation and efflux of vinblastine
      clearly indicated that MDR reversing effects of torilin would directly be
      associated with the increase of the intracellular accumulation of anticancer
      drugs by blocking the drug efflux. Furthermore, torilin increased the membrane
      ATPase activity from KB-V1 cells, suggesting that torilin might function by
      inhibiting drug transport mediated by P-glycoprotein.

PMID- 9619117
TI  - Antinociceptive and anti-inflammatory activities of limonin isolated from the
      fruits of Evodia rutaecarpa var. bodinieri.
AB  - Antinociceptive and anti-inflammatory effects of limonin isolated from the dried
      fruits of Evodia rutaecarpa var. bodinieri were investigated. Oral administration
      of 30 or 100 mg/kg limonin significantly decreased the frequency of licking and
      biting behavior within a unit of time at the late phase without affecting that of
      the early phase in the formalin test. Limonin inhibited the rise of vascular
      permeability induced by acetic acid and the increase of paw edema induced by
      carrageenin. Limonin also showed inhibitory effects on bradykinin-induced paw
      edema and arachidonic acid-induced ear swelling. These results suggest that
      limonin possesses an antinociceptive effect and the effect may be accompanied by
      an anti-inflammatory action, and that the antinociceptive activity in Evodiae
      Fructus is partially attributable to limonin.

PMID- 9619118
TI  - Sparing effect of procyanidins from Vitis vinifera on vitamin E: in vitro
      studies.
AB  - The sparing/recycling effect of a highly purified, high molecular weight fraction
      of catechin oligomers (procyanidins) from Vitis vinifera seeds on alpha
      tocopherol was studied in both homogeneous solution and in heterogeneous phase
      (phosphatidylcholine liposomes and red blood cells). By HPLC and electron spin
      resonance (ESR) spectroscopy we evidenced that tocopheroxyl radical, induced by
      reaction of alpha-tocopherol with the stable radical DPPH (2,2-diphenyl-1
      picrylhydrazyl) is recycled by procyanidins. In addition procyanidins
      significantly and dose-dependently spare vitamin E from consumption (HPLC
      monitoring) during the autooxidation phase of the HO-induced peroxidation of
      phosphatidylcholine, by 23% at the lowest concentration (0.5 microM) and by 65.5%
      at 3 microM. In this membrane model the combination of 0.5 microM procyanidins
      and 2 microM alpha-tocopherol results in a marked delay in the appearance of
      conjugated dienes in respect to the single antioxidants (synergistic
      interaction), while catechin showed to be active only at 5 microM. In red blood
      cells oxidatively stressed by UVB exposure, procyanidins at 0.1-1.0 microM
      prevent vitamin E loss, markedly decrease membrane lipid peroxidation, linearly
      related to the concentration of vitamin E in the membranes, and significantly
      delay the onset of hemolysis (catechin protects between 5 and 10 microM).

PMID- 9619119
TI  - Phytochemical and pharmacological studies of Guettarda acreana.
AB  - The present study examines the effects of the extracts [petroleum ether, CHCl3,
      CHCl3/MeOH (9:1) and MeOH], partially purified fractions and pure compounds from
      Guettarda acreana on the electrically induced contractions (E.C.I.) of the
      isolated guinea-pig ileum. The results of the experiments indicate that
      CHCl3/MeOH (9:1), MeOH extract, and the MeOH soluble part from CHCl3/MeOH extract
      tested at concentrations of 1.2, 2.5, and 5 micrograms/ml, dose-dependently
      reduced the guinea-pig ileum contractions. Furthermore, some partially purified
      fractions I-IV from the MeOH extract, each tested at the same concentrations of
      the extracts, and some pure compounds (6 x 10(-6), 3 x 10(-6), 1 x 10(-6) M)
      isolated from the above fractions significantly reduced, in a dose-dependent
      manner, the electrical contractions of the ileum. The active compounds were
      identified as the known indole alkaloids strictosidic acid, lyalosidic acid, 5
      alpha-carboxystrictosidine, strictosidine, and sickingine, as well as the known
      quinic acid derivatives 5-caffeoylquinic acid, 4,5-dicaffeoylquinic acid, and
      shikimic acid by spectral data. Two known quinovic acid glycosides and a new
      triterpenic glycoside, quinovic acid 3 beta-O-alpha-rhamnopyranosyl-(1-->3)-(beta
      glucopyranosyl-(1-->6)-beta- glucopyranoside, were also isolated and their
      structures established by NMR and M5 data.

PMID- 9619120
TI  - Influence of piperine on the pharmacokinetics of curcumin in animals and human
      volunteers.
AB  - The medicinal properties of curcumin obtained from Curcuma longa L. cannot be
      utilised because of poor bioavailability due to its rapid metabolism in the liver
      and intestinal wall. In this study, the effect of combining piperine, a known
      inhibitor of hepatic and intestinal glucuronidation, was evaluated on the
      bioavailability of curcumin in rats and healthy human volunteers. When curcumin
      was given alone, in the dose 2 g/kg to rats, moderate serum concentrations were
      achieved over a period of 4 h. Concomitant administration of piperine 20 mg/kg
      increased the serum concentration of curcumin for a short period of 1-2 h post
      drug. Time to maximum was significantly increased (P < 0.02) while elimination
      half life and clearance significantly decreased (P < 0.02), and the
      bioavailability was increased by 154%. On the other hand in humans after a dose
      of 2 g curcumin alone, serum levels were either undetectable or very low.
      Concomitant administration of piperine 20 mg produced much higher concentrations
      from 0.25 to 1 h post drug (P < 0.01 at 0.25 and 0.5 h; P < 0.001 at 1 h), the
      increase in bioavailability was 2000%. The study shows that in the dosages used,
      piperine enhances the serum concentration, extent of absorption and
      bioavailability of curcumin in both rats and humans with no adverse effects.

PMID- 9619121
TI  - Antimicrobial activity of magnolol and honokiol against periodontopathic
      microorganisms.
AB  - Magnolol (1) and honokiol (2), main compounds from the stem bark of Magnolia
      obovata Thunb., were evaluated for an antimicrobial activity against
      periodontopathic microorganisms, Porphyromonas gingivalis, Prevotella gingivalis,
      Actinobacillus actinomycetemcomitans, Capnocytophaga gingivalis, and Veillonella
      disper, and a cytotoxicity against human gingival fibroblasts and epithelial
      cells. Our results indicate that magnolol and honokiol, although less potent than
      chlorhexidine, show a significant antimicrobial activity against these
      microorganisms, and a relatively low cytotoxic effect on human gingival cells.
      Thus, it is suggested that magnolol and honokiol may have a potential therapeutic
      use as a safe oral antiseptic for the prevention and the treatment of periodontal
      disease.

PMID- 9619123
TI  - Isolation of lipolytic substances caffeine and 1,7-dimethylxanthine from the stem
      and rhizome of Sinomenium actum.
AB  - We attempted to isolate lipolytic substances from the stem and rhizome of
      Sinomenium actum Rehder et Wilson by using high-performance liquid chromatography
      (HPLC). S-I and S-II were isolated from the fractions showing lipolytic activity.
      S-I and S-II were identified as caffeine and 1,7-dimethylxanthine, respectively,
      by direct comparison with authentic samples. Caffeine (S-I) dose-dependently
      stimulated lipolytic activity in isolated fat cells of rats, at concentrations of
      500 to 1000 microM. 1,7-Dimethylxanthine (S-II) also stimulated lipolytic
      activity at concentrations of 500 to 1000 microM. Furthermore, we found that
      caffeine and 1,7-dimethylxanthine enhanced catecholamine-induced lipolysis at
      lower concentrations of 0.1 to 1 microM.

PMID- 9619122
TI  - Lupeol is the cytotoxic principle in the leaf extract of Dendropanax cf.
      querceti.
AB  - The crude ethanol extract from the leaves of Dendropanax cf. querceti
      (Araliaceae) from Monteverde, Costa Rica, exhibits cytotoxic activity against Hep
      G2, A-431, and H-4IIE tumor cell lines. The active component has been isolated by
      activity-directed separation and identified by 1H- and 13C-NMR spectroscopy as
      the triterpene lupeol. The mechanism of cytotoxic activity of lupeol has been
      determined to be inhibition of topoisomerase II.

PMID- 9619124
TI  - Pentacyclic triterpenoid saponin from Cyclamen coum.
AB  - A new triterpenoid saponin, coumoside B, has been isolated from the whole plant
      of Cyclamen coum. The structure of the compound 3 (C58H92O27) has been deduced by
      NMR (400 MHz) methods based on the 1H, 13C, DEPT, 1H-1H COSY, HETCOR, NOESY-NMR
      experiments, and FAB-mass spectrum. Compound 3 was shown to have the structure 16
      alpha-hydroxy-3 beta-[[[[beta-xylopyranosyl-(1-->2)]-[beta-glucopyranosyl-(1-
      >4)]- [beta-glucopyranosyl-(1-->2)]- alpha-arabinopyranosyl]-oxy]olean-12-eno
      30,28-lactone and is named coumoside B.

PMID- 9619125
TI  - Recombinant expression of alliin lyase from garlic (Allium sativum) in bacteria
      and yeasts.
AB  - Recombinant garlic alliin lyase was produced in Escherichia coli, Saccharomyces
      cerevisiae, and Pichia pastoris. A cDNA clone was obtained from garlic bulbs by
      PCR and introduced into suitable bacterial and yeast expression vectors. The
      recombinant alliin lyase forms inclusion bodies in all three host organisms,
      which are deposited in the cytoplasm. After cell lysis and harvesting by
      centrifugation, the inclusion bodies were solubilized in Zwittergent 3-14
      solution and refolded by stepwise dilution. Specific alliin lyase activity could
      be recovered by this procedure.

PMID- 9619126
TI  - Interpreting the WISC-R subtest scores of reading impaired children--a structural
      approach.
AB  - The problem of characterising more specifically the cognitive requirements
      involved in subtests from standardised measures of intelligence represents a main
      problem in the research on exceptional populations. A new way of classifying
      tests of mental abilities is presented. Rather than focusing on the content of a
      given test, the present classification system focuses on their structures. The
      classification system is applied to the WISC-R (Wechsler Intelligence Scale for
      Children--Revised, Wechsler, 1974). It will be used to interpret the IQ-profiles
      of a clinically defined sample of reading impaired children (N = 82). The basic
      finding of the study is that the structural complexity of a subtest influences
      the tests results of reading impaired children. This influence is interpreted as
      a consequence of poor procedural knowledge; i.e., poor knowledge about how to
      organise complex sets of data. It is suggested that teaching of metacognitive
      strategies could be an aid for reading impaired children.

PMID- 9619127
TI  - Differential validity of the Gottschalk-Gleser Anxiety Scales: is gender a
      moderator variable?
AB  - It can be hypothesized that affects like anxiety can be measured by content
      analysis of speech due to the phenomenon of mood congruent memory, which is found
      predominantly in females. To assess the effect of gender on the validity of the
      Gottschalk-Gleser Anxiety Scales, the standard procedure for obtaining verbal
      samples was followed and self-report measurements of comparable emotional
      constructs were applied concurrently. Measures of state and trait emotions were
      administered to 25 female and 25 male university students. In the female group 18
      significant convergent validity coefficients were found. For males, content
      analytic anxiety scores showed four significant correlations with concurrent self
      report scales. These results suggest that content analytic anxiety scores from
      female subjects may allow a more accurate prediction of state and trait emotions
      than anxiety scores from male subjects. Thus, gender might have a differential
      effect on the validity of the Gottschalk-Gleser Anxiety Scales.

PMID- 9619128
TI  - Neuroticism, coping and change in MCMI-II clinical syndromes: test of a mediator
      model.
AB  - The aim of the study was to examine prospectively whether coping mediated the
      relation between Neuroticism and change in different clinical mental syndromes.
      Assessments were conducted with 154 former psychiatric outpatients six and seven
      years after their initial contact with an outpatient clinic. Dispositional coping
      mediated the relation between Neuroticism and change in four of the nine clinical
      scales of the Millon Clinical Multiaxial Inventory (MCMI-II) (Millon, 1987). High
      Neuroticism led to coping strategies of disengagement and the venting of emotions
      and to a lack of problem-focused coping, which in turn translated into a relative
      increase on the MCMI-II scales. The mediator model of coping was found to apply
      to the MCMI-II scales 'somatoform disorder', 'dysthymia', 'alcohol dependence'
      and 'thought disorder'. Results are discussed under the perspective of an
      integration of the positions of the transactional theory of stress and
      personality psychology.

PMID- 9619129
TI  - Individuation, ego development and the quality of conflict negotiation in the
      family of adolescent girls.
AB  - Individuation, ego development and family negotiation of conflict were studied in
      27 Norwegian families with an adolescent daughter, 16-19 years, drawn from a
      larger sample to represent a rectangular distribution of ego development.
      Individuality and Connectedness (individuation) as conceptualized and scored by
      Condon et al. (1984) was modified and adapted to a Norwegian material. Four
      factors were extracted, one related to individuality (self-assertion and
      separateness) and two to connectedness (clarification and acceptance). Ego
      development, measured by the Washington University Sentence Completion Test
      (Loevinger & Wessler, 1970) was related to connectedness between mother and
      daughter and between father and daughter, but not to individuality. Maturity of
      conflict negotiation was positively related to connectedness between mother and
      daughter and negatively to individuality between father and daughter. It was
      argued that for women, individuality may not be a singular goal in ego
      development or in individuation and that self-other differentiation of identity
      and interests may develop within a close relationship and not only through
      separation.

PMID- 9619130
TI  - Age-associated memory impairment--pathological memory decline or normal aging?
AB  - The aim of the study was to determine whether the memory capacity of individuals
      with age-associated memory impairment (AAMI) over a period of approximately 3 1/2
      years declines more, if at all, than the memory capacity of persons without AAMI.
      Four computerized and three non-computerized memory tests, a naming test, and a
      test of visuo-motor speed were administered twice. Two estimates of intellectual
      capacity were made, one at the first examination and the other 3 1/2 years later.
      One person in the AAMI group (n = 44) developed vascular dementia. The group of
      AAMI subjects did less well on two of the seven memory tests after 3 1/2 years
      than they did initially; the control group (n = 18) had lower scores on one
      memory test at follow-up than they had previously. The data suggest that the
      memory capacity of subjects with AAMI is not pathologically impaired. The general
      intellectual level significantly influences whether an individual with memory
      complaints will be classified AAMI or not. People with high intelligence are less
      likely than people with lower intellectual capacity to fulfill the AAMI criteria.
      This suggests that AAMI lacks in construct validity.

PMID- 9619131
TI  - Rapid facial reactions to emotional facial expressions.
AB  - This study explored how rapidly emotion specific facial muscle reactions were
      elicited when subjects were exposed to pictures of angry and happy facial
      expressions. In three separate experiments, it was found that distinctive facial
      electromyographic reactions, i.e., greater Zygomaticus major muscle activity in
      response to happy than to angry stimuli and greater Corrugator supercilii muscle
      activity in response to angry stimuli, were detectable after only 300-400 ms of
      exposure. These findings demonstrate that facial reactions are quickly elicited,
      indicating that expressive emotional reactions can be very rapidly manifested and
      are perhaps controlled by fast operating facial affect programs.

PMID- 9619132
TI  - Personality characteristics of women with alcohol addiction: a Rorschach study of
      women in an early treatment programme.
AB  - This study identifies personality characteristics in a group of Swedish women (N
      = 60) attending their first treatment for alcohol problems. The treatment
      programme specifically addressed women in an early phase of their drinking
      career, and was called "Early Treatment of Women with Alcohol Addiction" (EWA).
      Rorschach personality profiles of the 60 women differed significantly in almost
      all investigated aspects in a psychopathological direction from norms reported by
      Exner for a reference group of female non-patients. The findings are consistent
      with the assumption that, although the EWA women were socially well-functioning
      and fairly early in their drinking career, they nevertheless reveal serious
      underlying psychopathology. Clinical implications of the findings are discussed.

PMID- 9619133
TI  - Beyond aspirin.

PMID- 9619134
TI  - B vitamins and heart-disease risk.

PMID- 9619135
TI  - Diabetes and blood pressure drugs.

PMID- 9619136
TI  - Can antibiotics prevent heart disease?

PMID- 9619137
TI  - No pain, some gain? Moderate activity improves blood-sugar levels.

PMID- 9619139
TI  - My doctor prescribed a particular cholesterol-lowering drug. When I went to the
      pharmacy, I found that my insurance company wanted me to use a different drug!
      The pharmacist called my doctor, who agreed with the change, and I got the second
      medication. What's going on?

PMID- 9619138
TI  - When I get out of bed in the morning, I often feel a little woozy for a minute,
      like I might faint. Is this something I should be worried about?

PMID- 9619140
TI  - My father died of a heart attack when he was 55 years old. I am in my late 40s
      and so far seem pretty healthy. I even go running five days a week. How important
      is my family history of heart disease?

PMID- 9619141
TI  - Addiction as a brain disease.

PMID- 9619142
TI  - Prevalence of psychopathology among children and adolescents.
AB  - OBJECTIVE: This study was done to update and expand information given in recent
      reviews, provide a more systematic critique of past research, identify current
      research trends and issues, and explore possible strategies for future research
      in child psychiatric epidemiology. METHOD: The authors identified and reviewed 52
      studies done over the past four decades that attempted to estimate the overall
      prevalence of child and adolescent psychiatric disorders. RESULTS: About as many
      studies have been published since 1980 as were published before. Sample sizes
      ranged from 58 to 8,462; most were in the 500-1,000 range. Studies were carried
      out in over 20 countries, most frequently the United States and the United
      Kingdom. Subjects' ages ranged from 1 to 18 years. Rutter's criteria were the
      most frequently used for case definition; more recent studies were more likely to
      use DSM criteria. The most frequently used interview was the Rutter schedule. The
      most common time frame for calculating prevalence was the present, followed by 6
      months and 1 year. Prevalence estimates of psychopathology ranged from
      approximately 1% to nearly 51% (mean = 15.8%). Median rates were 8% for
      preschoolers, 12% for preadolescents, 15% for adolescents, and 18% in studies
      including wider age ranges. CONCLUSIONS: The evidence is less informative than
      expected because of several problems that continue to plague research on child
      and adolescent disorders. These involve sampling, case ascertainment, case
      definition, and data analyses and presentation. Progress in understanding the
      epidemiology of child disorders will largely depend on whether future research
      successfully meets these challenges.

PMID- 9619143
TI  - Increased glutamatergic neurotransmission and oxidative stress after alcohol
      withdrawal.
AB  - OBJECTIVE: Neurophysiological and pathological effects of ethanol may be
      mediated, to an important extent, via the glutamatergic system. Animal studies
      indicate the acute effects of ethanol disrupt glutamatergic neurotransmission by
      inhibiting the response of the N-methyl-D-aspartate (NMDA) receptor. Persistent
      attenuation of glutamatergic neurotransmission by chronic ethanol exposure
      results in the compensatory up-regulation of NMDA receptors. Whether
      glutamatergic neurotransmission and oxidative stress are enhanced during ethanol
      withdrawal in humans is unknown. METHOD: CSF was obtained from 18 matched
      comparison subjects and from 18 patients with alcohol dependence 1 week and 1
      month after cessation of ethanol ingestion. CSF samples were analyzed for
      excitatory neurotransmitters, gamma-aminobutyric acid (GABA), and markers for
      oxidative stress. RESULTS: The alcohol-dependent patients' CSF levels of
      aspartate, glycine, and N-acetylaspartylglutamate were all higher than those of
      the comparison subjects, and their concentration of GABA was lower. In addition,
      there were significant correlations between excitatory neurotransmitters and
      oxidative stress markers, which suggest that the two mechanisms may play an
      interactive role in neurotoxicity mediated by ethanol withdrawal. CONCLUSIONS:
      The data suggest that augmentation of excitatory neurotransmission may lead to
      enhanced oxidative stress, which, in concert with reduced inhibitory
      neurotransmission, may contribute to the symptoms of ethanol withdrawal and
      associated neurotoxicity in humans. Whether these abnormalities represent a trait
      or state-dependent marker of ethanol dependence remains to be resolved.

PMID- 9619144
TI  - Clinical relevance of the distinction between alcohol dependence with and without
      a physiological component.
AB  - OBJECTIVE: DSM-IV indicates that diagnoses of substance dependence should be
      further characterized with regard to the presence of a physiological component,
      defined by tolerance or withdrawal. This study evaluated the possible meaning of
      this distinction in alcohol-dependent men and women. METHOD: As part of the
      Collaborative Study on the Genetics of Alcoholism, structured interviews were
      carried out with 3,395 DSM-III-R-defined alcohol-dependent individuals divided
      into 2,949 subjects (86.9%) with evidence of tolerance and/or withdrawal (group
      1), 51.3% of whom evidenced withdrawal symptoms, and 446 subjects (13.1%) without
      a physiological component (group 2). Data were evaluated to determine differences
      between the two groups. RESULTS: Group 1 reported greater severity of alcohol
      dependence as demonstrated by a larger maximum number of drinks in 24 hours, more
      persons reporting binges, more alcohol-related life problems, more relevant DSM
      III-R criteria endorsed, more physiological complications, and more alcohol
      related emotional/psychiatric symptoms such as depression and anxiety. Each of
      these severity indicators for problems in group 1 was significant in the presence
      of the others in a logistic regression, and similar items remained significant
      when tolerance alone, withdrawal alone, or their combination was used as the
      criterion for group 1 membership; however, for withdrawal a larger proportion of
      the variance was explained by the predictor variables. The regression results
      were independent of gender, proband status, and history of antisocial personality
      disorder. CONCLUSIONS: The results support the clinical relevance of
      distinguishing between alcohol-dependent patients with and without a
      physiological component. The data indicate a potential advantage to limiting that
      definition to withdrawal only.

PMID- 9619145
TI  - Genome scan of schizophrenia.
AB  - OBJECTIVE: The goal of this study was to identify chromosomal regions likely to
      contain schizophrenia susceptibility genes. METHOD: A genomewide map of 310
      microsatellite DNA markers with average spacing of 11 centimorgans was genotyped
      in 269 individuals--126 of them with schizophrenia-related psychoses--from 43
      pedigrees. Nonparametric linkage analysis was used to assess the pattern of
      allele sharing at each marker locus relative to the presence of disease. RESULTS:
      Nonparametric linkage scores did not reach a genomewide level of statistical
      significance for any marker. There were five chromosomal regions in which
      empirically derived p values reached nominal levels of significance at eight
      marker locations. There were p values less than 0.01 at chromosomes 2q (with the
      peak value in this region at D2S410) and 10q (D10S1239), and there were p values
      less than 0.05 at chromosomes 4q (D4S2623), 9q (D9S257), and 11q (D11S2002).
      CONCLUSIONS: The results do not support the hypothesis that a single gene causes
      a large increase in the risk of schizophrenia. The sample (like most others being
      studied for psychiatric disorders) has limited power to detect genes of small
      effect or those that are determinants of risk in a small proportion of families.
      All of the most positive results could be due to chance, or some could reflect
      weak linkage (genes of small effect). Multicenter studies may be useful in the
      effort to identify chromosomal regions most likely to contain schizophrenia
      susceptibility genes.

PMID- 9619146
TI  - Positive and negative symptom response to clozapine in schizophrenic patients
      with and without the deficit syndrome.
AB  - OBJECTIVE: In a preliminary report, the authors observed that clozapine was
      superior to haloperidol in the treatment of positive and negative symptoms in
      stable outpatients with schizophrenia. In this final report, they examine the
      effects of clozapine on positive and negative symptoms in patients with and
      without the deficit syndrome to determine which patients receive the positive
      symptom advantage of clozapine and the extent of clozapine's therapeutic effects
      on negative symptoms. In addition, they examine the long-term effects of
      clozapine on positive, negative, and affective symptoms, social and occupational
      functioning, and quality of life. METHOD: Seventy-five outpatients with
      schizophrenia, who met retrospective and prospective criteria for residual
      positive or negative symptoms, were entered into a 10-week double-blind, parallel
      groups comparison of clozapine and haloperidol. Patients who completed the double
      blind study were then entered into a 1-year open-label clozapine study. RESULTS:
      For patients who completed the 10-week double-blind study, clozapine was superior
      to haloperidol in treating positive symptoms. This effect was not observed in the
      intent-to-treat analyses. There was no evidence of any superior efficacy or long
      term effect of clozapine on primary or secondary negative symptoms. Long-term
      clozapine treatment was associated with significant improvements in social and
      occupational functioning but not in overall quality of life. CONCLUSIONS: For
      schizophrenic patients who are able to tolerate clozapine therapy, clozapine has
      superior efficacy for positive symptoms but not negative symptoms and is
      associated with long-term improvements in social and occupational functioning for
      patients with and without the deficit syndrome.

PMID- 9619147
TI  - Increased striatal dopamine transmission in schizophrenia: confirmation in a
      second cohort.
AB  - OBJECTIVE: The authors previously observed an increase in striatal dopamine
      transmission following amphetamine challenge in 15 untreated patients with
      schizophrenia compared to 15 matched healthy subjects. The purpose of this study
      was to replicate this finding in a new cohort of schizophrenic patients and
      healthy subjects. METHOD: Fifteen patients with schizophrenia and 15 healthy
      subjects matched for age, gender, ethnicity, and parental socioeconomic status
      were recruited for this study. Patients fulfilled DSM-IV criteria for
      schizophrenia, had no history of alcohol or substance abuse or dependence, and
      were neuroleptic free for a minimum of 21 days. Amphetamine-induced dopamine
      release was assessed by the reduction in dopamine D2 receptor availability
      induced by an acute amphetamine challenge (0.3 mg/kg, intravenous bolus).
      Reduction in D2 receptor availability was measured with single photon emission
      computed tomography and the D2 receptor radiotracer [123I]IBZM. RESULTS: No
      differences were observed between patients with schizophrenia and the comparison
      group in D2 receptor availability at baseline. Patients with schizophrenia
      exhibited a significantly larger reduction in D2 receptor availability following
      acute amphetamine challenge than the comparison group. In this study, the effect
      size was smaller than in the first study. Excess dopamine release following
      amphetamine was associated with transient emergence or worsening of positive
      symptoms. CONCLUSIONS: In this new cohort of subjects the authors replicated
      their initial observation of a dysregulation of striatal dopamine release in
      schizophrenia.

PMID- 9619148
TI  - Sex differences in the striatal dopamine D2 receptor binding characteristics in
      vivo.
AB  - OBJECTIVE: The authors investigated whether striatal dopamine D2 receptor binding
      characteristics in vivo are similar in men and women and whether there are sex
      related differences in the decline in D2 receptor density due to aging. METHOD:
      Striatal D2 receptor density (Bmax), affinity (Kd), and binding potential
      (Bmax/Kd) were measured with positron emission tomography and [11C]raclopride in
      54 healthy subjects (33 men and 21 women). RESULTS: Women had generally lower D2
      receptor affinity than men, and this difference was statistically significant in
      the left striatum. Bmax and Bmax/Kd tended to decline with age twice as fast in
      men as in women, but the difference did not reach statistical significance.
      CONCLUSIONS: These results confirm the age-related reduction of D2 receptor
      density and binding potential in both sexes in vivo. The lower D2 receptor
      affinity suggests an increased endogenous striatal dopamine concentration in
      women. This may have implications for the differential vulnerability of men and
      women to psychiatric disorders like schizophrenia and alcohol and substance
      dependence.

PMID- 9619149
TI  - Decreased caudate volume in neuroleptic-naive psychotic patients.
AB  - OBJECTIVE: Previous studies, mostly involving neuroleptic-treated patients, have
      suggested enlarged basal ganglia size in schizophrenia. The authors sought to
      examine basal ganglia volume in neuroleptic-naive psychotic patients. METHOD:
      Magnetic resonance imaging volumetric studies were conducted in newly diagnosed
      neuroleptic-naive schizophrenic and non-schizophrenic psychotic patients and in
      matched healthy comparison subjects. RESULTS: Both patient groups had bilaterally
      reduced caudate, but not putamen, volumes, compared to the healthy subjects,
      after adjustment for intracranial volume. CONCLUSIONS: Decreases in caudate
      volume in newly diagnosed psychotic patients may be related to the primary
      pathophysiology of these disorders; prior observations of increased caudate
      volume may reflect effects of neuroleptic treatment.

PMID- 9619150
TI  - Apolipoprotein E epsilon 4 allele and whole brain atrophy in late-onset
      Alzheimer's disease.
AB  - OBJECTIVE: Diffuse brain atrophy is one of the gross pathological features of
      Alzheimer's disease and is a result of degenerative changes. The epsilon 4 allele
      of apolipoprotein E (APOE) is a risk factor or susceptibility gene in late-onset
      sporadic Alzheimer's disease and may influence the pathological changes
      associated with the disease. The aim of this study was to examine the
      relationship between the APOE epsilon 4 allele and whole brain atrophy. METHOD:
      Whole brain volume was quantified by using high-resolution magnetic resonance
      imaging and the computerized brain segmentation technique in 178 patients with
      late-onset sporadic Alzheimer's disease who carried no APOE epsilon 4 alleles (N
      = 62), one epsilon 4 allele (N = 93), or two (N = 23) and had comparable clinical
      severity of dementia. RESULTS: An apparent positive correlation was found between
      normalized whole brain volume (relative to total intracranial volume) and number
      of APOE epsilon 4 alleles; i.e., patients carrying two APOE epsilon 4 alleles had
      the least brain atrophy. This association between the APOE epsilon 4 allele and
      brain volume was similar in women and men and was independent of age, level of
      education, duration of illness since symptom onset, and severity of dementia.
      CONCLUSIONS: The results indicate that cognitive dysfunction progresses before
      severe brain atrophy develops in patients carrying the APOE epsilon 4 allele and
      suggest that an APOE epsilon 4-allele-related mechanism that affects neuronal
      function before a decrement in brain matter is involved in the development of
      dementia.

PMID- 9619151
TI  - Increasing required neural response to expose abnormal brain function in mild
      versus moderate or severe Alzheimer's disease: PET study using parametric visual
      stimulation.
AB  - OBJECTIVE: The authors examined the interaction of Alzheimer's disease severity
      and visual stimulus complexity in relation to regional brain function. METHOD:
      Each subject had five positron emission tomography [15]H2O scans while wearing
      goggles containing a grid of red lights embedded into each lens. Regional
      cerebral blood flow (CBF) was measured at 0 Hz and while lights were flashed
      alternately into the two eyes at 1, 4, 7, and 14 Hz. Changes in regional CBF from
      the 0-Hz baseline were measured at each frequency in 19 healthy subjects (mean
      age = 65 years, SD = 11), 10 patients with mild Alzheimer's disease (mean age =
      69, SD = 5; Mini-Mental State score > or = 20), and 11 patients with moderate to
      severe Alzheimer's disease (mean age = 73, SD = 12; Mini-Mental State score < or
      = 19). RESULTS: As pattern-flash frequency increased, CBF responses in the
      comparison group included biphasic rising then falling in the striate cortex,
      linear increase in visual association areas, linear decrease in many anterior
      areas, and a peak at 1 Hz in V5/MT. Despite equivalent resting CBF and CBF
      responses to low frequencies among all groups, the groups with Alzheimer's
      disease had significantly smaller CBF responses than the comparison group at the
      frequency producing the largest response in the comparison group in many brain
      regions. Also, patients with moderate/severe dementia had smaller responses at
      frequencies producing intermediate responses in comparison subjects. CONCLUSIONS:
      Functional failure was demonstrated in patients with mild dementia when large
      neural responses were required and in patients with moderate/severe dementia when
      large and intermediate responses were required.

PMID- 9619153
TI  - Frequency of dissociative disorders among psychiatric inpatients in a Turkish
      University Clinic.
AB  - OBJECTIVE: The aim of this study was to determine the rate of dissociative
      disorders among psychiatric inpatients in a university clinic in Turkey. METHOD:
      The Dissociative Experiences Scale was used to screen 166 consecutive inpatients
      admitted to the psychiatry clinic of a university hospital. The patients who had
      scores higher than 30 were matched for age and gender with 19 of the patients who
      scored below 10 on the scale. The patients in both groups were then interviewed
      with the Dissociative Disorders Interview Schedule by interviewers who were blind
      to their diagnoses and scores on the Dissociative Experiences Scale. Patients who
      were diagnosed as having a dissociative disorder according to the Dissociative
      Disorders Interview Schedule were then interviewed by a clinician. RESULTS:
      Twenty-four (14.5%) of the 166 patients had a score higher than 30 on the
      Dissociative Experiences Scale; 17 patients (10.2%) were diagnosed as having a
      dissociative disorder according to the Dissociative Disorders Interview Schedule.
      Nine patients (5.4%) had clinically confirmed dissociative identity disorder.
      CONCLUSIONS: A considerable proportion of the psychiatric inpatients in a Turkish
      university psychiatry clinic had dissociative disorder. Clinicians who work in
      general psychiatric inpatient units should be alert for chronic complex
      dissociative disorders.

PMID- 9619152
TI  - Effects of age at onset of first lifetime episode of recurrent major depression
      on treatment response and illness course in elderly patients.
AB  - OBJECTIVE: The goal of this study was to examine treatment outcome differences in
      relation to age at onset of first lifetime episode of recurrent major depression
      in elderly patients. METHOD: Patients were grouped as having early-onset (N =
      129) or late-onset (N = 58) depression. Early onset was defined as having a first
      lifetime episode of major depression at age 59 or earlier; late onset was defined
      as age 60 or later. The two groups of patients were compared with respect to
      demographic and clinical characteristics, types of treatment given (nortriptyline
      and interpersonal psychotherapy), and treatment outcomes. RESULTS: The groups did
      not differ in the percentage of patients who remitted, recovered, or relapsed
      during continuation treatment or in the percentage who experienced a recurrence
      of major depression during the first year of maintenance treatment. However,
      early-onset patients took 5-6 weeks longer to achieve remission than did late
      onset patients, and a higher proportion had a history of suicide attempts.
      CONCLUSIONS: These data suggest that age at lifetime onset of recurrent major
      depression does not influence short- or long-term treatment response in elderly
      patients treated with combined interpersonal psychotherapy and nortriptyline,
      with the exception of slowing the speed of remission in early-onset cases.
      Difference in remission speed may reflect the greater number of previous episodes
      in the early-onset patients. Nevertheless, the likelihood of a longer time to
      remission, together with a higher rate of past suicide attempts, suggests that
      elderly depressed patients with a history of early-onset illness need
      particularly careful management.

PMID- 9619154
TI  - Relationship between dissociation, childhood sexual abuse, childhood physical
      abuse, and mental illness in a general population sample.
AB  - OBJECTIVE: The aim of this study was to examine the relationship between
      childhood sexual abuse, childhood physical abuse, current psychiatric illness,
      and measures of dissociation in an adult population. METHOD: The authors used a
      randomly selected sample of 1,028 individuals. Each subject completed a
      semistructured face-to-face interview that included measures of childhood sexual
      abuse, childhood physical abuse, DSM-III-R psychiatric diagnoses, and selected
      items from the Dissociative Experiences Scale. RESULTS: Many individuals
      experienced occasional dissociative symptoms, and 6.3% of the population suffered
      from three or more frequently occurring dissociative symptoms. Among these
      individuals, the rate of childhood sexual abuse was two and one-half times as
      high, the rate of physical abuse was five times as high, and the rate of current
      psychiatric disorder was four times as high as the respective rates for the other
      subjects. Logistic regression modeling showed that physical abuse and current
      psychiatric illness were directly related to a high rate of dissociative symptoms
      but sexual abuse was not. The influence of sexual abuse was due to its
      associations with current psychiatric illness and with childhood physical abuse.
      Childhood physical abuse was not directly related to current psychiatric illness.
      Its association appeared to be mediated by its link to childhood sexual abuse.
      CONCLUSIONS: This study confirms that a small proportion (approximately 6%) of
      the general population suffer from high levels of dissociative symptoms. It calls
      into question the hypothesized direct relationship between childhood sexual abuse
      and adult dissociative symptoms.

PMID- 9619155
TI  - Effect of darkness on acoustic startle in Vietnam veterans with PTSD.
AB  - OBJECTIVE: Exaggerated startle is a symptom of posttraumatic stress disorder
      (PTSD), but empirical studies have not consistently documented elevated baseline
      startle in PTSD. The authors proposed in a previous study that Vietnam veterans
      with PTSD exhibit exaggerated startle only under stressful conditions. They
      reported that darkness facilitated startle in humans, suggesting that the startle
      reflex is sensitive to the aversive nature of darkness. In the present study they
      tested the hypothesis that the magnitude of facilitation of startle by darkness
      would be greater in Vietnam veterans with PTSD than in comparison groups of
      subjects without PTSD. Prepulse inhibition was also investigated. METHOD: The
      magnitude of startle and prepulse inhibition were assessed in alternating periods
      of darkness and light in 19 nonmedicated Vietnam veterans with PTSD, 13 Vietnam
      veterans without PTSD, and 20 civilians without PTSD. RESULTS: The overall
      startle level was higher in the veterans with PTSD than in either of the two
      groups of subjects without PTSD. Startle was facilitated by darkness, and the
      magnitude of this facilitation was greater in the veterans with PTSD than in the
      civilians without PTSD, but it was not greater in the veterans without PTSD.
      Prepulse inhibition was not affected by darkness and did not significantly differ
      among groups. CONCLUSIONS: Contrary to the hypothesis, elevated sensitivity to
      darkness was specific to individuals with combat experience, not to individuals
      with PTSD, perhaps because veterans had become aversively conditioned to darkness
      during their combat experiences. The more general increase in startle reactivity
      in the veterans with PTSD is consistent with clinical observations and
      descriptions of symptoms in DSM-IV.

PMID- 9619156
TI  - Family structure and depressive symptoms in men preceding and following the birth
      of a child. The Avon Longitudinal Study of Pregnancy and Childhood Study Team.
AB  - OBJECTIVE: The prevalence and etiology of pre- and postpartum depressive symptoms
      in women in a variety of family forms have been well documented, but relatively
      little research has been conducted on the adjustment of their male partners. The
      authors' goals in this study were 1) to estimate rates of depression during the
      pregnancy and 8 weeks following the birth of a child in a large representative
      community sample of fathers in different family structures and 2) to explore the
      role of stressful life events, social and emotional support, the quality of the
      partner relationship, and socioeconomic circumstances. METHOD: This study
      describes the relations of family setting and other correlates to men's
      depressive symptoms during the pregnancies (18 weeks gestation, on average) and 8
      weeks after the births of children for 7,018 partners of female participants in
      the Avon Longitudinal Study of Pregnancy and Childhood. RESULTS: Men living in
      stepfamilies had-significantly higher levels of depressive symptoms before and
      after the birth than did men in more traditional families. The effect of
      stepfamily status on depression was mediated by education, life events, social
      support, social network, and level of aggression in the partnership. CONCLUSIONS:
      There are similarities in the patterns and correlates of depression after the
      birth of a child for men and women. These findings point to the importance of
      family and partnership ecology in the adjustment of men before and after the
      birth of a child.

PMID- 9619157
TI  - Predictors of a medical-offset effect among patients receiving antidepressant
      therapy.
AB  - OBJECTIVE: Characteristics of patients receiving antidepressant therapy were
      examined to identify factors that may be associated with a medical-offset effect.
      METHOD: In a retrospective study, the authors analyzed claims data from a large
      health insurer in New England. The study subjects included 1,661 persons
      initiating treatment for depression with selective serotonin reuptake inhibitors
      or tricyclic antidepressants between July 1991 and June 1993. RESULTS: Patients
      with anxiety disorders, coronary heart disease, cancer, and chronic fatigue
      syndrome and those remaining on their initial regimens of antidepressant therapy
      for at least 6 months were more likely to experience significant reductions in
      the costs of medical care services. The number of visits to mental health
      providers had no effect on the costs of medical services. CONCLUSIONS: Specific
      comorbid conditions and sustained use of antidepressant drugs may be associated
      with a medical-offset effect for patients receiving treatment for depression.

PMID- 9619158
TI  - Bipolar disorder and panic disorder in families: an analysis of chromosome 18
      data.
AB  - OBJECTIVE: The authors performed an analysis of their published chromosome 18
      linkage data on 28 families in which there was bipolar disorder to test the
      potential of comorbid panic disorder to define a genetic subtype of bipolar
      disorder. METHOD: Families ascertained through probands with bipolar I disorder
      were stratified into three groups based on a history of panic disorder, panic
      attacks, or no panic attacks in the probands. Multipoint nonparametric linkage
      analysis was performed on data from bipolar I and II family members in each
      group. RESULTS: Linkage scores for five consecutive 18q marker loci were highest
      in the families of the probands with panic disorder and lowest for the families
      of the probands without panic attacks. CONCLUSIONS: This study supports the
      authors' previously reported clinical hypothesis of a genetic subtype of bipolar
      disorder identified by comorbid panic disorder. The hypothesis merits prospective
      testing.

PMID- 9619159
TI  - Elevated striatal dopamine transporters during acute cocaine abstinence as
      measured by [123I] beta-CIT SPECT.
AB  - OBJECTIVE: The authors examined whether striatal dopamine transporters were
      altered in acutely (96 hours or less) abstinent cocaine-abusing subjects, as
      suggested by postmortem studies. METHOD: [123I] beta-CIT and single photon
      emission computed tomography were used to assess striatal dopamine transporter
      levels in 28 cocaine-abusing subjects and 24 comparison subjects matched as a
      group for age and gender. RESULTS: Results showed a significant (approximately
      20%) elevation in striatal V3" values in acutely abstinent cocaine-abusing
      subjects relative to comparison subjects. An inverse correlation between dopamine
      transporter level and Hamilton Depression Rating Scale score was also observed.
      CONCLUSIONS: These findings indicate more modest elevations in striatal dopamine
      transporters in cocaine-abusing subjects than noted in previous postmortem
      reports and suggest a possible relationship between cocaine-related depression
      and dopamine transporter binding.

PMID- 9619160
TI  - Association between catechol O-methyltransferase genotype and violence in
      schizophrenia and schizoaffective disorder.
AB  - OBJECTIVE: The authors previously reported a relationship between an allele
      encoding the low activity variant of catechol O-methyltransferase (COMT) and
      aggressive behavior in schizophrenic patients. This study replicates and extends
      these findings by using more direct measures of violent behavior. METHOD: Fifty
      five white patients (34 men, 21 women) with DSM-IV diagnoses of schizophrenia or
      schizoaffective disorder were selected to form two groups (violent and
      nonviolent) on the basis of history of aggressive behavior. COMT genotypes were
      determined by restriction fragment length polymorphism analysis. RESULTS: A
      significant association was found between COMT genotype and history of violent
      behavior. Sixty-four percent of patients homozygous for the low-activity COMT
      allele were violent; 80% of patients homozygous for the high-activity allele were
      nonviolent. CONCLUSIONS: The gene determining the activity of an important
      regulatory enzyme in catecholamine inactivation is associated with violent
      behavior in patients with schizophrenia and schizoaffective disorder.

PMID- 9619161
TI  - Neuroendocrine evidence that clozapine's serotonergic antagonism is relevant to
      its efficacy in treating hallucinations and other positive schizophrenic
      symptoms.
AB  - OBJECTIVE: The authors examined the effect of prolonged clozapine treatment on
      central serotonergic (5-HT) function in schizophrenia. METHOD: Prolactin
      responses to the 5-HT releasing agent d-fenfluramine were measured in two groups
      of 10 schizophrenic subjects. The first group was tested twice, before and after
      a mean of 10 weeks of clozapine treatment. The second group was tested after a
      mean of 20 months of clozapine treatment. RESULTS: The prolactin response was
      significantly blunted in these 20 patients treated with clozapine. There was a
      significant positive correlation between d-fenfluramine-evoked prolactin release
      and the overall positive symptom score and the hallucination and delusion
      subscores of the Scale for the Assessment of Positive Symptoms. CONCLUSIONS:
      Blunted 5-HT-mediated prolactin responses in schizophrenic patients receiving
      clozapine monotherapy for up to 20 months were correlated with reductions in
      positive symptoms. This suggests that 5-HT antagonism is relevant to clozapine's
      efficacy in alleviating hallucinations and other positive schizophrenic symptoms.

PMID- 9619162
TI  - Relationship between posttraumatic stress disorder characteristics of Holocaust
      survivors and their adult offspring.
AB  - OBJECTIVE: There is controversy regarding the long-lasting effects of the
      Holocaust on the adult children of Holocaust survivors. In the present study the
      authors examined the relationship between posttraumatic stress disorder (PTSD)
      characteristics of Holocaust survivors and their adult children to determine
      whether differences in symptom severity or diagnostic status of parents would be
      associated with similar characteristics in their adult children. METHOD:
      Holocaust survivors (N = 22) and their offspring (N = 22) were interviewed with
      several instruments to assess lifetime trauma history, effect of trauma on one's
      life, level of intrusive and avoidance symptoms in response to reminders of the
      Holocaust, current and lifetime PTSD, and current and lifetime axis I psychiatric
      disorder other than PTSD. RESULTS: There were significant relationships between
      parents and children regarding the effect of trauma on one's life and level of
      intrusive, but not avoidance, symptoms in response to reminders of the Holocaust.
      Offspring with traumatic events were more likely to develop PTSD if their parents
      had PTSD. CONCLUSIONS: Symptoms in offspring may be related to presence and
      severity of symptoms in the parent. Furthermore, PTSD in the parent may be a risk
      factor for PTSD in offspring.

PMID- 9619163
TI  - Dissociative identity disorder in psychiatric inpatients.
AB  - OBJECTIVE: The aim of this study was to replicate reports of a high rate of
      dissociative identity disorder in psychiatric inpatients. METHOD: Subjects were
      100 randomly selected women, 16-50 years old, who had recently been admitted to
      an acute psychiatric hospital. Diagnoses were made by two interviewers through
      use of the Structured Clinical Interview for DSM-IV Dissociative Disorders.
      RESULTS: One percent (N = 1) of the interviewed subjects had dissociative
      identity disorder. CONCLUSIONS: Contrary to previous studies, the authors found a
      low rate of dissociative identity disorder, perhaps because of the different
      methodology used.

PMID- 9619164
TI  - Worsening of obsessive-compulsive symptoms following treatment with olanzapine.

PMID- 9619165
TI  - Risperidone-associated agranulocytosis.

PMID- 9619166
TI  - The broken heart.

PMID- 9619167
TI  - Biliary dyskinesia: natural history and surgical results.
AB  - Patients with biliary dyskinesia have symptoms consistent with biliary colic and
      an abnormal gallbladder ejection fraction (GEF) in the absence of cholelithiasis.
      Cholecystokinin hepatobiliary scan quantifies gallbladder function and may assist
      in selecting patients with acalculous biliary pain who would benefit from
      cholecystectomy. Seventy-eight patients with an abnormal GEF (< 35%) on
      cholecystokinin hepatobiliary scan without cholelithiasis were studied
      retrospectively. Patients were divided into groups based on diagnosis and
      treatment. In Group I, the patients who underwent cholecystectomy, 80 per cent
      (35 of 44) had complete symptomatic resolution whereas the remaining 20 per cent
      (9 of 44) had symptomatic improvement. Pathology reports demonstrated chronic
      cholecystitis in 95 per cent of specimens. Group II were patients with symptoms
      attributable to biliary dyskinesia, but did not undergo cholecystectomy.
      Persistence of symptoms was noted in 75 per cent (18 of 24) of patients whereas
      25 per cent (6 of 24) had symptomatic resolution without any treatment. Group III
      consisted of patients with an abnormal ejection fraction who had improvement of
      symptoms after treatment for an alternative diagnosis (n = 10). These findings
      suggest that an abnormal ejection fraction does not always indicate gallbladder
      disease. Alternative diagnoses must be investigated and treated. Patients with
      persistent biliary type symptoms in combination with an abnormal GEF in the
      absence of other attributable causes can expect a favorable response to
      cholecystectomy.

PMID- 9619168
TI  - Are chest X-rays mandatory following central venous recatheterization over a
      wire?
AB  - Exchange of a central venous catheter (CVC) over a guidewire is a frequent
      clinical procedure, especially in surgical intensive care units. At most
      hospitals, a chest X-ray (CXR) is obtained routinely after recatheterization to
      confirm accurate catheter placement and to rule out complications such as
      pneumothorax. We hypothesized that the incidence of complications after central
      venous recatheterization over a guidewire is too low to justify automatic
      performance and the associated expense of a routine postprocedure CXR. Initially
      we undertook a retrospective study of a total of 295 patients with a Swan-Ganz
      catheter (SGC), of which 92 SGCs were exchanged over a guidewire for a CVC
      between July 1, 1994, and June 30, 1996, at a university-affiliated community
      hospital. Age, gender, duration of SGC placement, type of central catheter used
      for exchange with the SGC, and CXRs and their reports were noted. From July 1,
      1996, to October 1, 1997, the study has been continued prospectively. Thus far,
      in this ongoing investigation, we have identified 505 patients (201 prospective)
      who had a SGC placed, 210 (116 prospective) of whom had their SGC removed
      electively, leaving the SGC introducer in place for advancement of a guidewire,
      and subsequent replacement by a CVC. Of all the patients with a SGC, 40 per cent
      had the SGC replaced with a CVC over a guidewire, and follow-up CXRs and their
      reports confirmed that all exchanged triple lumen catheter tips were
      appropriately positioned in the superior vena cava with zero complications. With
      the advent of managed care, a savings of $115/CXR (one view X-ray and reading
      cost at our hospital) would be gained without the added risk of radiation
      exposure to the patient if a CXR were not mandatory after an uncomplicated
      guidewire replacement of a central line. It appears from these data that a CXR is
      not justified as a routine study after replacement of all CVCs over a wire from
      the standpoints of both patient risk and expense. Conscientious physical
      examination together with good clinical acumen and judgement in evaluating
      patients after replacement of a CVC over a guidewire are likely to obviate the
      currently mandated postprocedure CXR, reserving its use for selected patients.

PMID- 9619169
TI  - Initial cervical exploration for parathyroidectomy is not benefited by
      preoperative localization studies.
AB  - Published data is controversial as to the ability of preoperative localization
      studies (PLS) to enhance the outcome of initial cervical exploration in patients
      with primary hyperparathyroidism (PHPT). One surgeon's experience was reviewed to
      compare surgical success, operative time, and morbidity of initial cervical
      exploration for PHPT in patients who had undergone PLS versus those who had not.
      From August 1991 to September 1997, 95 patients who had not undergone prior
      central cervical exploration presented for surgical management of PHPT. Sixty
      seven patients underwent initial cervical exploration without any PLS having been
      performed (Group A). Twenty-eight patients underwent PLS, either alone or in
      combination, before surgical intervention (Group B). Analysis of intergroup
      variability was conducted upon the data available using a two-tailed t test for
      independent samples. In addition, the sensitivities and positive predictive
      values of the PLS were calculated using study reports and operative and
      histologic findings. There was no statistically significant difference in
      surgical success between those patients who had PLS and those that did not
      undergo PLS. Sixty-four of 67 patients (95.5%) not having PLS were cured with
      initial surgery, while 27 of 28 patients (96.4%) who had PLS were surgically
      cured. Mean postoperative calcium and intact parathormone levels were similar
      between the two groups, and the mean operative time did not differ. Permanent
      hypocalcemia occurred in one patient, and five patients had transient hoarseness.
      Thirty-six total PLS were obtained at an average cost of $752.68/patient, and
      seven patients underwent multiple tests. Overall, sestamibi scan had the highest
      positive predictive value (81%). For adenomatous disease alone, sestamibi scan
      was the most sensitive (83%). Our study shows that for matched groups limited to
      age, sex, and clinical diagnosis, the use of PLS did not shorten operative time,
      decrease complication frequency, nor alter the success of the operation as
      measured by postoperative calcium and parathormone levels. Therefore, routine use
      of preoperative localization studies before initial cervical exploration for PHPT
      cannot be recommended.

PMID- 9619170
TI  - Quality of life and antireflux medication use following laparoscopic Nissen
      fundoplication.
AB  - With the advent of minimally invasive techniques, the surgical treatment of
      gastroesophageal reflux disease has received renewed interest. The efficacy of
      laparoscopic Nissen fundoplication in eliminating reflux has been documented.
      This study was undertaken to determine changes in quality of life and cost of
      antireflux medications after laparoscopic Nissen fundoplication. One hundred
      patients undergoing laparoscopic Nissen fundoplication between 1992 and 1997
      completed questionnaires assessing changes in pre- and postoperative cost and
      number of antireflux medications, reflux symptoms, and quality of life. The
      average number of antireflux medications was significantly reduced (1.8 versus
      0.3, P < 0.0001) as was the average monthly cost ($170 versus $30, P < 0.0001).
      Patients reported significant (P < 0.05) symptomatic improvement in postprandial
      heartburn, nocturnal heartburn, postprandial nausea, postprandial vomiting,
      dysphagia, and gas/bloating. Patients in this series noted fewer symptoms and
      used fewer antireflux medications at less cost after laparoscopic Nissen
      fundoplication. Symptoms commonly thought of as complications of fundoplication
      (vomiting, dysphagia, gas/bloating) were less common after fundoplication. This
      report documents the efficacy of laparoscopic fundoplication in improving quality
      of life and reducing use and cost of antireflux medications.

PMID- 9619171
TI  - The outcome of laparoscopic Heller myotomy without antireflux procedure in
      patients with achalasia.
AB  - We retrospectively reviewed 30 patients with achalasia (18 males, 12 females)
      undergoing laparoscopic Heller myotomy without antireflux procedure to determine
      relief of dysphagia and prevalence of postoperative gastroesophageal reflux.
      Preoperative symptoms were obtained by history alone before 1996 and by
      standardized questionnaire after September 1996. Twenty-nine patients (97%) had
      dysphagia, 22 patients (73%) had regurgitation, 21 patients (70%) had weight
      loss, 7 patients (23%) had heartburn, and 4 patients (13%) had nocturnal
      aspiration. The first 3 patients were done thoracoscopically, with the subsequent
      27 patients performed laparoscopically; 4 cases (13%; 1 thoracoscopic and 3
      laparoscopic) were converted. The mean postoperative stay was 1.9 days (1-6
      days). One patient underwent repeat laparoscopic myotomy for persistent
      dysphagia. Twenty-eight patients (93%) were available for follow-up. Patients
      were asked on a standardized questionnaire to grade their relief of dysphagia,
      regurgitation, and heartburn. Good to excellent relief of dysphagia was obtained
      in 25 patients (89%), whereas 3 patients (11%) continued to have significant
      dysphagia postoperatively. Twenty-four patients (86%) had little or no
      regurgitation. Four patients (14%) had frequent regurgitation. Twenty-four
      patients (89%) reported little or no heartburn. Three patients (11%) reported
      significant postoperative heartburn. Laparoscopic Heller esophagomyotomy without
      antireflux procedure provides excellent symptomatic relief of dysphagia in
      patients with achalasia. Early follow-up suggests that minimal occurrence of
      symptomatic postoperative reflux can be achieved without performing an antireflux
      procedure.

PMID- 9619172
TI  - Comparison of sequential compression devices and foot pumps for prophylaxis of
      deep venous thrombosis in high-risk trauma patients.
AB  - Multiple-trauma patients are at increased risk for deep venous thrombosis (DVT)
      but are also at increased risk of bleeding, and the use of heparin may be
      contraindicated. Sequential pneumatic compression devices (SCDs) are an
      alternative for DVT prophylaxis. However, lower extremity fracture or soft tissue
      injury may preclude their use. In these circumstances, foot pumps (FPs) are often
      substituted, yet little clinical data exist to support their use. We identified
      184 consecutive high-risk trauma patients who received DVT prophylaxis with
      compression devices. We reviewed demographic data, mechanism of injury, Injury
      Severity Score, injury pattern, and method of prophylaxis. Generally, SCDs were
      preferred, but FPs were substituted in patients with lower extremity injuries.
      Occurrences of DVT or pulmonary embolism were also noted. Patients surviving less
      than 48 hours were excluded. SCDs were used in 118 patients (64%) and FPs in 66
      patients (34%). There were no differences in age, Injury Severity Score, or
      presence of shock on admission. As expected, FP patients were more likely to have
      lower extremity fractures (65 vs 26%; P < 0.05) and were also more likely to have
      associated pelvic fracture (59 vs 25%; P < 0.05) and chest injury (61 vs 26%, P <
      0.05). There was no difference in the incidence of head injury, although SCD
      patients had more severe head injuries (Glasgow Coma Score, 7.9 vs 10.5; P <
      0.05). The overall incidence of DVT was 5.4 per cent (10 of 184), with no
      differences between the two groups (SCD 7% vs FP 3%). Three patients had a
      pulmonary embolism (FP, two; SCD, one), none of which were fatal. Compression
      devices provide adequate DVT prophylaxis with a low failure rate (3-8%) and no
      device-related complications. FPs appear to be a reasonable alternative in the
      high-risk trauma patient when lower extremity fractures precludes use of SCD.

PMID- 9619173
TI  - Racial and gender differences in outcome after carotid endarterectomy.
AB  - Women and minorities were underrepresented in trials demonstrating carotid
      endarterectomy (CEA) is superior to medical treatment for significant carotid
      stenosis. These trials also revealed that the benefit of CEA is largely
      determined by the incidence of operative complications. Our series of 429 CEAs
      reflects a more diverse population (41% women, 24% blacks). We questioned if
      outcome was related to race, gender or other factors. Stroke occurred after 4.9
      per cent of operations, cardiac events after 3 per cent, and death after 2 per
      cent. No factors correlated with cardiac events. Diabetes, smoking, neurologic
      symptoms, shunting, and patch closure did not correlate with complications.
      Chronic renal insufficiency (CRI), emergent operation, and operation by
      neurosurgeons correlated with stroke. Black females (BF) had significantly more
      strokes than did others (16% versus 3%). More BF had CRI, but their higher
      complication rate persisted when CRI patients were excluded. More BF were
      hypertensive (98% versus 74%), but hypertension did not correlate with
      complications. However, severe acute perioperative hypertension was common in BF
      experiencing complications and may be related to the differences observed. These
      findings highlight the need for better understanding of racial and gender outcome
      differences after CEA in order to improve risks and allow modification of
      selection criteria for high risk groups.

PMID- 9619174
TI  - Local recurrence of breast cancer after cytological evaluation of lumpectomy
      margins.
AB  - Successful breast conservation therapy with optimal cosmesis requires adequate
      tumor excision and negative tumor margins. Therefore, more sensitive techniques
      are being developed to identify lumpectomy margins intraoperatively with greater
      accuracy. Unidentified microscopic disease is seemingly responsible for a local
      recurrence rate of up to 25 per cent 3 to 5 years after lumpectomy and
      radiotherapy for breast cancer patients. As a result, Moffitt Cancer Center has
      routinely used an intraoperative touch preparation cytology (TPC) protocol to
      evaluate the entire resected surface of all lumpectomies. In addition, resection
      margins were also evaluated by gross examination and by standard histology. In
      rare instances frozen sections were used to evaluate tumor margins. In this study
      701 consecutive lumpectomy specimens were evaluated by TPC during the period of 9
      years with a mean follow-up of 3.5 years. Local cancer recurrence was 2.7 per
      cent (mean recurrence, 2.53 years), in women whose lumpectomy margins were
      evaluated by TPC. Of interest, a local recurrence rate of 14.6 per cent was
      observed in patients who had referral lumpectomies evaluated by conventional
      histopathology. This study suggests that accurate margin assessment with TPC
      plays an important role in the control of local recurrence after breast
      conservation therapy. Therefore, we conclude the routine use of intraoperative
      TPC provides rapid, reliable, topographically accurate identification of residual
      microscopic disease at lumpectomy margins.

PMID- 9619175
TI  - Efficacy of reverse transcriptase-polymerase chain reaction screening for
      micrometastic disease in axillary lymph nodes of breast cancer patients.
AB  - Pathologic examination of axillary lymph nodes (ALNs) may miss micrometastases in
      30 per cent of breast cancer patients. We have developed a multimarker reverse
      transcriptase-polymerase chain reaction (RT-PCR)-based screening method that
      detects histopathologically positive ALNs with a 5 per cent false-negative rate.
      The purpose of this study was to compare this RT-PCR methodology with
      histopathology with regard to sensitivity and cost. Pathologically negative ALNs
      from 35 breast cancer patients were re-evaluated by a single pathologist in a
      blinded fashion using serial sectioning with immunohistochemical staining.
      Histopathologic results were then compared with those of RT-PCR. Cost analysis
      was performed based on standard charges for these methods. RT-PCR identified
      micrometastases in 14 of 35 pathologically negative nodes. Serial sectioning and
      immunohistochemical staining identified micrometastases in two cases, with RT-PCR
      positive for one of these. The charge per specimen for performing routine
      histopathologic examination was $380, serial sectioning and immunohistochemical
      staining $787, and RT-PCR $125. RT-PCR appears to be more sensitive at detecting
      ALN micrometastasis than histopathologic examination even with serial sectioning
      and immunohistochemical staining. If micrometastatic breast cancer detected by RT
      PCR proves to be clinically relevant, it could be a more effective screening
      methodology with significant cost savings as compared to currently available
      pathologic examinations.

PMID- 9619176
TI  - Early gastric cancer and Helicobacter pylori: 34 years of experience at Charity
      Hospital in New Orleans.
AB  - Good survival rates have been reported for resected early gastric adenocarcinoma
      (EGC) in patients found via screening procedures. However, the prevalence of
      Helicobacter pylori in EGC in unscreened populations is unclear. The major
      purpose of this investigation was to analyze the clinical experience and
      incidence of H. pylori in unscreened patients presenting with EGC at Charity
      Hospital over a 34-year period. From 1963 through 1997, the tumor registry at
      Charity Hospital compiled data on 2497 patients evaluated for gastric carcinoma.
      Of these patients, 26 (1%) had lesions that were confined to the mucosa or
      submucosa, i.e., T1N0M0 (American Joint Commission on Cancer classification).
      Pathology specimens and medical records were retrieved for confirmation of
      diagnosis and retrospective analysis for H. pylori. H. pylori was analyzed by
      Steiner staining and immunohistochemistry using a polyclonal antibody. EGC was
      detected in 12 men and 14 women with a mean age of 62 years. Upper
      gastrointestinal X-ray studies were performed on 19 of the 26 patients and failed
      to conclusively demonstrate a lesion in any case. Endoscopy was performed on 22
      patients, and preoperative biopsies were positive in 95 per cent of these.
      Operative procedures included 2 local excisions and 22 subtotal and 2 total
      gastrectomies. No extended nodal dissections were performed. Microscopic
      evaluation revealed lesions limited to the mucosa in 63 per cent of cases and
      involving the submucosa in 37 per cent of the cases. Of the 14 patients evaluable
      of H. pylori, 79 per cent were positive for the bacterium. The status of 2
      patients is unknown, and only 1 patient died of the original gastric cancer, for
      a disease-free survival of 96 per cent. The 5-year and 10-year overall survival
      rates were calculated to be 50 per cent and 21 per cent, respectively, when all
      causes of death were taken into consideration. Median follow-up of the survivors
      was 64 months. Resection of early gastric carcinoma in unscreened patients
      without extended lymphadenectomy yielded excellent results. H. pylori was present
      in 79 per cent of cases. These data suggest an association between H. pylori and
      EGC. Whether H. pylori infection is an etiologic factor in gastric cancer remains
      an area of active research.

PMID- 9619177
TI  - Nonoperative management of liver and/or splenic injuries: effect on resident
      surgical experience.
AB  - Changes in the management of trauma over the past few years are significantly
      affecting postgraduate surgical education, with the lack of operative trauma
      experience being a major concern in some programs. This problem is accentuated in
      residency programs that obtain their trauma caseload primarily from blunt injury.
      Our experience over the past 6 years confirms that the growing trend toward
      nonoperative management of blunt liver and spleen injuries in adults is likely to
      exacerbate this problem. Blunt trauma admissions to our Level I trauma center
      increased from 2888 from 1991 through 1993 (group A) to 3587 from 1994 through
      1996 (group B). Liver and/or splenic injuries occurred with equal frequency in
      both groups. Whereas diagnostic peritoneal lavage was used in 26 per cent of
      group A, its use dropped to 2 per cent in group B as abdominal computerized
      tomography was used more frequently to evaluate these patients. Nonoperative
      management increased from 10 per cent of group A to 54 per cent of group B. As a
      result, therapeutic laparotomies dropped from 85 in group A (58% of patients with
      liver/splenic injuries) to 74 (35%) in group B and nontherapeutic laparotomies
      from 48 (33%) to 23 (11%). While the evolution in the management of blunt liver
      and splenic injuries has resulted in the avoidance of nontherapeutic
      laparotomies, the operative caseload available to surgical housestaff has been
      adversely affected. Although the Residency Review Committee has stressed the
      importance of the critical care management of these patients, the criteria used
      to evaluate the number of trauma cases in postgraduate surgical education may
      need to be revised.

PMID- 9619178
TI  - The clinical complexity of splenic vein thrombosis.
AB  - Upper gastrointestinal hemorrhage secondary to splenic vein thrombosis is a
      curable form of localized portal hypertension when treated with splenectomy. A
      high index of suspicion is necessary in order to promptly diagnose and treat this
      underrecognized condition that is most commonly caused by inflammation or
      neoplasm of the pancreas. The triad of isolated gastric varices, splenomegaly,
      and normal hepatic function is classic; it is not uncommon, however, for patients
      to have only some or even none of these conditions. Mesenteric angiography with
      venous phase imaging is the gold standard of diagnosis. Ultrasound and CT may
      identify splenic vein thrombosis, but are most helpful in delineating concomitant
      upper abdominal pathology. Early recognition and intervention allow associated
      underlying conditions to be treated under the same anesthetic with minimal
      morbidity and mortality.

PMID- 9619179
TI  - Colorectal cancer in patients under forty: presentation and outcome.
AB  - Colorectal cancer is the third most frequent malignancy in adults of both sexes
      in this country, with 90 per cent of patients diagnosed after age 50 years. This
      disease is unusual in patients under 40 years of age, and controversy persists as
      to prognosis in this subset of patients. Patients diagnosed with invasive
      adenocarcinoma of the colon and rectum from 1985 to 1997 were identified. They
      were then grouped according to age (< 40 or > or = 40). Charts were reviewed with
      respect to patient epidemiologic characteristics, clinical presentation, tumor
      staging, and survival. Twelve women and 24 men less than 40 years of age (median,
      31 years/range, 13-39 years) were diagnosed with colorectal adenocarcinomas. This
      represented 8.6 per cent of the total patients diagnosed with colorectal cancers
      during this time. Thirty-five (97%) had symptoms (pain, blood per rectum, weight
      loss, or alteration in bowel habits) before diagnosis, and 23 (64%) had multiple
      symptoms. Younger patients had more poorly differentiated tumors (28%) and more
      mucinous adenocarcinomas (26%) than the older group. Younger patients were more
      likely to present with stage III or IV disease (78%) as well. Despite these
      findings, the median survival for younger patients was no different than the
      older patients when compared by stage. Colorectal cancer in young adults is rare,
      but should be considered in the differential diagnosis for all patients with
      gastrointestinal symptomatology. The presentation of these patients is not unlike
      that of older patients. Those patients with early-stage disease should be treated
      aggressively, as long-term survival may be anticipated, whereas the outcome for
      those with metastatic disease is poor.

PMID- 9619180
TI  - Recurrent inguinal hernia: preferred operative approach.
AB  - Inguinal herniorrhaphy remains one of the most common general surgical
      operations, with approximately 10 to 20 per cent performed for recurrence.
      Subsequent repairs provide considerable technical challenge, as well as
      substantially greater risk of developing further recurrence. Mesh repair is
      advocated by several specialized hernia centers, demonstrating re-recurrence
      rates less than 2 per cent. Detractors of this repair include cost, technical
      difficulty, and risk for infection. The purpose of this study was to compare
      results of mesh and nonmesh repairs for recurrent inguinal hernia, either using
      an anterior or posterior approach, at a large teaching institution. From January
      1, 1985, to December 31, 1994, 146 patients underwent repair for recurrent
      inguinal hernia at the Veterans Administration Hospital at Memphis, Tennessee.
      Patients were stratified by type of repair: Lichtenstein (Mesh), open anterior
      (OA), Bassini, Marcy, McVay, Shouldice, and preperitoneal with or without mesh.
      Patient ages and weights were similar between groups. Mean operative time for
      Mesh repair (104 +/- 4 minutes) was longer than that for OA repairs (80 +/- 5
      minutes, P < 0.05) or preperitoneal without mesh repairs (92 +/- 5 minutes, P <
      0.05). Mesh-based posterior repairs had the longest operative times (116 +/- 5
      minutes). Hospital stay averaged 2.8 +/- 0.3 days, similar among all groups. One
      wound infection (1.0%) occurred in patients undergoing Mesh repair, which
      required operative drainage. No patient required removal of mesh. Two patients in
      the Mesh group (5.9%) developed recurrence compared with four recurrences (18.0%)
      in patients undergoing OA repairs. Only one patient with a mesh-based posterior
      repair recurred (1.9%) compared to eight without mesh (21.6%, P < 0.01). Follow
      up ranged from 2 to 12 years. Repair of recurrent inguinal hernia using either an
      anterior or posterior mesh repair technique, performed at a teaching facility,
      provides superior recurrence rates without increasing risk for infection or
      length of stay. Preperitoneal mesh based repair is the preferred technique.

PMID- 9619181
TI  - Neonatal necrotizing enterocolitis: the long-term perspective.
AB  - Ten years' experience with neonatal necrotizing enterocolitis (NNEC) was reviewed
      retrospectively to determine long-term survival and quality of life and to
      analyze risk factors associated with in-hospital mortality. Institutional records
      were queried to identify all neonates who required emergent surgical intervention
      for NNEC. These records were then reviewed and survivors' families interviewed by
      phone to determine patient status, persistent gastrointestinal problems, and
      overall quality of life. Once identified, long-term survivors (LTSs) were
      compared to in-hospital deaths by the analysis of birth weight, gestational age,
      time interval from birth to diagnosis, indications for laparotomy, and extent of
      intestinal involvement. Between 1986 and 1996, 69 patients required surgical
      intervention for NNEC. Eleven patients were lost to follow-up. Of the remaining
      58 patients, 31 were ultimately discharged home, with 28 patients having survived
      an average of 4.18 years. The acute, or in-hospital, mortality rate was 39.1 per
      cent. Infants who died did so within an average of 23 days postoperatively, and
      those who were discharged home required an average of 121 days of inpatient
      convalescence. Twenty-one of the 28 LTSs achieved a normal quality of life with
      no persistent health problems. One patient required a hepatic-intestinal
      transplant, and another six had minor problems with frequent diarrhea. Average
      birth weight, age at NNEC diagnosis, and gestational age were not significantly
      different between LTSs and those with acute deaths. Aggressive in-hospital care
      is warranted for infants with NNEC. The excellent quality of life achieved in 75
      per cent of survivors implies that the expense of heroic surgical care for these
      seriously ill premature infants is a worthwhile investment.

PMID- 9619182
TI  - Combination endovascular and open treatment of peripheral arterial occlusive
      disease performed by surgeons.
AB  - The endovascular treatment of peripheral arterial occlusive disease has
      historically been performed by interventional radiologists and cardiologists.
      With additional training in endovascular techniques, surgeons become uniquely
      suited to manage arterial lesions with both endovascular and conventional
      surgical techniques. Over a 14-month period, 13 patients underwent combination
      endovascular and open reconstruction on limbs with peripheral arterial occlusive
      disease. There were 10 males and 3 females. The mean age was 66 years. All
      procedures were performed in the operating room by surgery residents under the
      direct supervision of vascular surgeons. After intraoperative angiography, 26
      arterial lesions underwent percutaneous transluminal angioplasty (aorta, 1;
      common iliac, 14; external iliac, 10; superficial femoral, 1). Twenty-five of 26
      lesions were further treated with intraluminal stent placement, the lone
      exception being a case of superficial femoral artery angioplasty. Concomitant
      open reconstruction was performed on all limbs, 14 as outflow and 1 as inflow.
      There were two cases of procedural morbidity and one perioperative death
      secondary to myocardial infarction. There were no wound-related complications.
      The mean ankle-brachial index of the affected lower extremity improved from 0.41
      (+/- 0.15) to 0.74 (+/- 0.14) at 30 days. Mean follow-up was 8 months (range, 2
      14). Based on our early experience, simultaneous combination endovascular and
      open reconstruction of multisegment arterial occlusive disease can be performed
      safely and efficiently by surgeons.

PMID- 9619183
TI  - Clinical pathways for general surgeons: emergency appendectomy with rupture.

PMID- 9619184
TI  - The pain matrix and neuropathic pain.

PMID- 9619185
TI  - Temporary interference in human lateral premotor cortex suggests dominance for
      the selection of movements. A study using transcranial magnetic stimulation.
AB  - It is known that damage to the left hemisphere can lead to movement deficits, and
      that patients with apraxia have difficulty in selecting movements.
      Neurophysiological recording studies and lesion studies have shown that the
      premotor cortex is important for the selection of movements in monkeys. In this
      study we used transcranial magnetic stimulation (TMS) to disrupt the processing
      in human premotor cortex. We applied TMS to normal healthy volunteers over the
      premotor and primary motor areas while they carried out choice reaction time and
      simple reaction-time tasks. We measured response times of either hand as subjects
      were stimulated over the left and right hemisphere separately. We found that we
      were able to delay responses by stimulating at short cue-stimulus intervals (100
      140 ms) over premotor cortex and at longer cue-stimulus intervals (300-340 ms)
      over primary motor cortex while subjects performed the choice reaction-time task
      with the contralateral hand. We were also able to delay responses with the
      ipsilateral hand while stimulating over the left premotor cortex, but not while
      stimulating over the right premotor cortex or either sensorimotor cortex.
      Premotor cortex stimulation alone disrupts an early stage of movement selection;
      motor cortex stimulation disrupts the movements at a later stage of execution.
      There was no distinguishing short cue-stimulus interval effect when premotor
      cortex was stimulated in the simple reaction time paradigm, where the movement
      selection demands of the task are kept to a minimum. We conclude that the
      premotor cortex is important for selecting movements after a visual cue and that
      the left hemisphere is dominant for the rapid selection of action.

PMID- 9619186
TI  - Abnormal motor unit synchronization of antagonist muscles underlies pathological
      co-contraction in upper limb dystonia.
AB  - The aim of this study was to examine the pathophysiological mechanisms underlying
      co-contraction in patients with dystonia (n = 6) and writer's cramp (n = 5).
      Multi-unit needle and surface EMGs were recorded from extensor carpi radialis
      (ECR) and flexor carpi radialis (FCR) muscles during motor tasks that elicited
      dystonia or writer's cramp. The EMGs from ECR and FCR were recorded
      simultaneously and analysed using cross-correlation analysis. Similar recordings
      were obtained from healthy age- and sex-matched control subjects (n = 8). Despite
      co-contraction of the muscles, cross-correlograms from the healthy subjects did
      not reveal evidence of motor unit synchronization. Cross-correlograms from the
      dystonic subjects revealed a central peak with a median duration of 37 ms,
      indicating broad-peak motor unit synchronization. Cross-correlograms from
      patients with writer's cramp were either flat or modulated by a 11-12-Hz tremor.
      Frequency-domain analysis of ECR and FCR EMGs demonstrated significant coherence
      in the patients with dystonia and writer's cramp. These results indicate that co
      contraction in dystonia is neurophysiologically distinct from voluntary co
      contraction and is produced by abnormal synchronization of presynaptic inputs to
      antagonist motor neuron pools. ECR and FCR co-contraction in writer's cramp may
      be a compensatory process under voluntary control.

PMID- 9619187
TI  - Dissociating executive mechanisms of task control following frontal lobe damage
      and Parkinson's disease.
AB  - Twelve patients with focal damage of the frontal cortex and 12 patients with
      mild, medicated, early stage Parkinson's disease switched between letter- and
      digit=naming tasks on every second trial of a task-switching paradigm. Compared
      with age- and IQ-matched control performance, patients with left-sided, but not
      right-sided, frontal damage exhibited markedly increased time costs associated
      with these predictable switches only when there was a general incidence of
      interference or 'crosstalk' between the tasks, and particularly so when the
      available task cues were relatively weak and arbitrary. The same patients also
      showed evidence of an increased sensitivity to the facilitatory and inhibitory
      effects of previous processing, when required to switch between tasks. Both
      groups of patients (with left- or right-sided frontal damage) exhibited slow,
      disorganized performance early in practice. In contrast to these frontal effects,
      the Parkinson's disease patients showed little indication of larger time costs of
      task switches but they did show progressive increases in the error costs, while
      age- and IQ-matched control subjects showed reductions. We propose that while
      both left and right frontal cortical areas are involved in the organization of
      cognitive and motor processes in situations involving novel task demands, only
      the left frontal cortex is involved in the dynamic reconfiguring between already
      established task-sets, and specifically, that it is the site of an executive
      mechanism responsible for the modulation of exogenous task-set activity. Finally,
      dopaminergic transmission, along the nigrostriatal pathway, may be implicated in
      sustaining various cognitive and motor processes over prolonged periods,
      including the operation of those executive control mechanisms that accomplish
      reconfiguring between task-sets.

PMID- 9619188
TI  - Pure somaesthetic alexia: somaesthetic-verbal disconnection for letters.
AB  - We studied a patient who manifested a bilateral reading disorder through the
      somaesthetic modality, without deficit of elementary tactile sensation or tactile
      object naming, due to a left parietal infarct. Detailed investigation established
      the following points. (i) The patient showed normal function on elementary
      somaesthetic examination, normal function on high level tactile perception,
      except for minimal impairment of the right hand on the two-point discrimination
      test, and normal latencies on the somatosensory evoked potential in both hands.
      (ii) The patient had difficulty in reading letters using any somaesthetic
      strategy (graphaesthesia, directional joint kinaesthesia and active touch) with
      either hand. (iii) On a same-different judgement task, the patient's performance
      with the right hand was slightly defective on graphaesthesia and active touch,
      but performance with the left hand was within the normal range for all of the
      strategies. The patient's disorder was highly category specific and modality
      specific, indicating that somaesthetic letter reading can be disrupted not only
      independent of other high level somaesthetic functions, like object recognition,
      but also independent of other modes of reading functions, such as visual reading.
      A lesion involving the intraparietal sulcus, the upper part of the inferior
      parietal lobule and the adjacent white matter in the left hemisphere may be
      capable of compromising the pathways for somaesthetic letter reading with both
      hands.

PMID- 9619189
TI  - Strength-duration properties of sensory and motor axons in amyotrophic lateral
      sclerosis.
AB  - In normal subjects, the strength-duration time constant is longer for cutaneous
      afferents than for motor axons, probably because the former express a greater non
      inactivating (persistent) Na+ conductance that is active at threshold. Using a
      threshold-tracking system the strength-duration properties of cutaneous afferents
      and motor axons were recorded from 23 patients with amyotrophic lateral
      sclerosis, and compared with those of 32 healthy subjects. In control subjects
      and patients, the strength-duration time constant of sensory fibres declined with
      age, and there was no difference between the two groups when age was taken into
      account. The motor time constant did not change with age when expressed as a
      percentage of the time constant for sensory fibres in the same nerve, but was
      significantly longer for the patients than control subjects. In addition, motor
      rheobase was significantly lower for the patients, when expressed as a percentage
      of sensory rheobase. There was an inverse relationship between the time constant
      and rheobase for sensory and motor axons, and this was the same for the patients
      and the control subjects, suggesting that the variations in time constant within
      and between the groups were related to the expression of a common factor.
      Measurements of refractoriness and supernormality provided no evidence for a
      difference in resting membrane potential between the patients and control
      subjects. These findings are consistent with the interpretation that motor axons
      of the patients with amyotrophic lateral sclerosis have a greater persistent Na+
      conductance than normal motor axons. This could contribute to the ectopic
      activity responsible for fasciculation.

PMID- 9619190
TI  - Age effects on brain activity associated with episodic memory retrieval. An
      electrophysiological study.
AB  - Electrophysiological correlates of episodic memory retrieval (recollection) were
      investigated in a young (18-30 years) and an older group (62-79 years) of healthy
      subjects (n = 16 per group). At study, subjects listened to words spoken in
      either a male or a female voice, and were instructed to perform one of two tasks
      depending on the voice in which the item was spoken. At test, subjects made
      initial old/new judgements to visually presented words and, for words judged old,
      either indicated in which voice they had heard the word at study (source task),
      or whether the 'remembered' or 'knew' they had heard the word at study
      ('remember/know' task). The accuracy of the initial recognition decision did not
      differ between the two groups. However, young subjects were significantly more
      accurate in their source judgements than the older group. The magnitudes and
      topographical distributions of differences between event related potentials to
      successfully recollected words and new words were indistinguishable for the two
      tasks. These event-related potential effects were also equivalent in magnitude
      and scalp topography in the two age groups, the only difference between the
      groups being a relative delay in the onset of the effects at some electrode sites
      in the older subjects. These findings are consistent with the proposal that the
      processes supporting episodic retrieval, including those dependent upon the
      prefrontal cortex, are relatively unaffected by advancing age.

PMID- 9619191
TI  - PET activation of the medial temporal lobe in learning.
AB  - Regional cerebral blood flow was examined during multiple-trial learning in
      healthy volunteers. On the basis that incremental learning from trial to trial is
      severely impaired in neuropsychological studies of patients with medial temporal
      lesions, we predicted that medial temporal activation might be particularly
      associated with incremental gains in learning. On the other hand, we predicted
      that frontal activations would not show any increase during incremental learning,
      and might even diminish. PET recordings were undertaken while subjects were
      presented visually with a 15-word list in one of three conditions: a list in
      which a single word was repeated 15 times (S), a list of novel words (N), and a
      list which was repeated from before (R). We demonstrated that statistically
      significant incremental learning did occur when word lists were repeated in (R)
      trials. The subtraction of novel minus repeated conditions (N-R) was associated
      with left medial temporal as well as left prefrontal activations, whereas the
      opposite (R-N) subtraction gave rise to right prefrontal and precuneal
      activations. In particular, incremental learning during the repeated trials (R)
      identified a left medial temporal activation, as predicted, but the left frontal
      activation was no longer evident. We suggest that the left medial temporal region
      is not only activated by novel, to-be-learned stimuli, but it also contributes to
      incremental learning as part of a network involved in 'binding' or
      'consolidating' new memories. The right frontal and precuneal regions, which
      participate in the repeated retrieval and rehearsal of already learned memories,
      are also involved in this network. The left frontal region is implicated in the
      more 'effortful' or elaborative aspects of memory.

PMID- 9619192
TI  - A clinicopathological study of autism.
AB  - A neuropathological study of autism was established and brain tissue examined
      from six mentally handicapped subjects with autism. Clinical and educational
      records were obtained and standardized diagnostic interviews conducted with the
      parents of cases not seen before death. Four of the six brains were
      megalencephalic, and areas of cortical abnormality were identified in four cases.
      There were also developmental abnormalities of the brainstem, particularly of the
      inferior olives. Purkinje cell number was reduced in all the adult cases, and
      this reduction was sometimes accompanied by gliosis. The findings do not support
      previous claims of localized neurodevelopmental abnormalities. They do point to
      the likely involvement of the cerebral cortex in autism.

PMID- 9619193
TI  - The cross-over effect in unilateral neglect. Modelling detailed data in the line
      bisection task.
AB  - The line-bisection task is the standard assessment of unilateral visual neglect.
      It supplies one effect, the crossover effect, that challenges models of neglect:
      in left neglect, the rightward displacement of the midpoint of the line becomes a
      left displacement for small lines. We review the various attempts to account for
      the cross-over effect, before describing a computational model of performance in
      the line-bisection task that produces a cross-over effect quite naturally in its
      damaged state. The model trades on aspects of several current theories of
      neglect, including independent attentional processing in the two hemispheres,
      each of which possesses an attentional gradient in which the contralateral field
      is accentuated. We assume a small residual noise, along the same gradient, in the
      damaged hemisphere. When lesioned to simulate right hemisphere damage, the model
      produces line bisections similar to human performance, in terms of the
      relationship with line length, a variable cross-over point for the smaller lines,
      and an amelioration of performance with leftside, but not rightside cueing.

PMID- 9619194
TI  - Cognitive impairment in families with pure autosomal dominant hereditary spastic
      paraparesis.
AB  - In the course of a study of a large family with pure autosomal dominant
      hereditary spastic paraparesis (AD-HSP), mild cognitive impairment was found in
      older family members. In order to determine if cognitive impairment occurred more
      frequently in families with pure AD-HSP than normally expected, a case control
      study of cognitive function in HSP was undertaken. Thirty-one patients, from 12
      kindreds with pure AD-HSP, matched with 31 healthy control subjects for age, sex
      and years of education, were assessed for evidence of cognitive impairment using
      the Cambridge Cognitive Examination (CAMCOG). Twenty unaffected siblings matched
      with twenty healthy control subjects were similarly assessed. The total CAMCOG
      score in the affected group (mean 89.26/107, SD 11.08, 95% confidence interval
      85.2-94.49) compared with the control group (mean 96.52/107, SD 5.52, 95%
      confidence interval 94.49-98.54) was significantly reduced (P = 0.0003). There
      were also significant abnormalities in three out of the nine subsets including
      memory (P = 0.0002), language comprehension (P = 0.0166) and language expression
      (P = 0.0025). The differences between the groups were due to cognitive impairment
      appearing after the age of 50 years in patients with AD-HSP; CAMCOG scores before
      this age were similar to control scores. There was also a minor non-significant
      difference in total CAMCOG score for the unaffected siblings (mean 93.7/107, SD
      8.54, 95% confidence interval 89.70-97.70) compared with the control group (mean
      97.9/107, SD 4.61, 95% confidence interval 95.7-100.1) (P < 0.02). This study
      demonstrates that mild cognitive impairment develops after the age of 50 years in
      patients with pure AD-HSP and is further evidence of degeneration in other
      systems in this disorder.

PMID- 9619195
TI  - Neural activation during acute capsaicin-evoked pain and allodynia assessed with
      PET.
AB  - The PET H2 15O-bolus method was used to image regional brain activity in normal
      human subjects during intense pain induced by intradermal injection of capsaicin
      and during post-capsaicin mechanical allodynia (the perception of pain from a
      normally non-painful stimulus). Images of regional cerebral blood flow were
      acquired during six conditions: (i) rest; (ii) light brushing of the forearm;
      (iii) forearm intradermal injection of capsaicin, (iv) and (v) the waning phases
      of capsaicin pain; and (vi) allodynia. Allodynia was produced by light brushing
      adjacent to the capsaicin injection site after ongoing pain from the capsaicin
      injection had completely subsided. Capsaicin treatment produced activation in
      many discrete brain regions which we classified as subserving four main
      functions: sensation-perception (primary somatosensory cortex, thalamus and
      insula); attention (anterior cingulate cortex); descending pain control
      (periaqueductal grey); and an extensive network related to sensory-motor
      integration (supplementary motor cortex, bilateral putamen and insula, anterior
      lobe and vermis of the cerebellum and superior colliculus). Comparison of the
      noxious and non-noxious stimuli yielded several new insights into neural
      organization of pain and tactile sensations. Capsaicin pain, which had no
      concomitant tactile component, produced little or no activation in secondary
      somatosensory cortex (SII), whereas light brushing produced a prominent
      activation of SII, suggesting a differential sensitivity of SII to tactile versus
      painful stimuli. The cerebellar vermis was strongly activated by capsaicin,
      whereas light brush and experimental allodynia produced little or no activation,
      suggesting a selective association with C-fibre stimulation and nociceptive
      second-order spinal neurons. The experimental allodynia activated a network that
      partially overlapped those activated by both pain and light brush alone. Unlike
      capsaicin-induced pain, allodynia was characterized by bilateral activation of
      inferior prefrontal cortex, suggesting that prefrontal responses to pain are
      context dependent.

PMID- 9619196
TI  - Abnormal basal ganglia outflow in Parkinson's disease identified with PET.
      Implications for higher cortical functions.
AB  - In this study we examined the effects of striatal dopamine depletion on cortical
      and subcortical blood flow changes during two tasks known to involve
      frontostriatal circuitry. Regional cerebral blood flow was measured in six
      patients with moderate Parkinson's disease and in six age-matched control
      subjects while they performed easy and difficult versions of a modified Tower of
      London planning task and a mnemonic variant of this task that required short-term
      retention and reproduction of problem solutions, as well as a control condition
      that involved identical visual stimuli and motor responses. Relative to control
      conditions, the planning task was associated with an increase in cerebral blood
      flow centred on the internal segment of the right globus pallidus in the age
      matched control subjects, and a decrease in the same region in the patients with
      Parkinson's disease. A similar inverse relationship between the task-specific
      blood flow change observed in the control group and that observed in the
      Parkinson's disease patients was not found in any other subcortical or cortical
      area examined, including regions of the dorsolateral frontal cortex known to be
      involved in this task. When blood flow in the spatial working memory task was
      examined, a similarly specific dissociation between the two groups of subjects
      was observed at similar coordinates in the right pallidum. We conclude that
      striatal dopamine depletion disrupts the normal pattern of basal ganglia outflow
      in Parkinson's disease and consequently, affects the expression of frontal-lobe
      functions by interrupting normal transmission of information through
      frontostriatal circuitry.

PMID- 9619197
TI  - An open-labelled clinical and electrophysiological study of 3,4 diaminopyridine
      in the treatment of fatigue in multiple sclerosis.
AB  - We studied the electrophysiological parameters of motor performance in eight
      patients with multiple sclerosis and troublesome fatigue, before and after
      treatment with 3,4-diaminopyridine. Symptomatic fatigue was evaluated by the
      Krupp Fatigue Severity Score and motor performance of adductor pollicis by
      transcranial magnetic stimulation, rapid voluntary movements and a fatiguing
      exercise test of a sustained 45-s isometric contraction. The motor tests revealed
      baseline abnormal motor function and substantial central fatigue. After a 3-week
      course of 3,4-diaminopyridine (25-60 mg/day), six out of the eight patients
      reported substantial improvement in fatigue and the group showed slightly less
      fatigue on the exercise test. Other electrophysiological tests of motor function
      were unchanged. The findings suggest that 3,4-diaminopyridine may play a role in
      the symptomatic treatment of fatigue in multiple sclerosis. However, the
      mechanism behind such a benefit in fatigue remains unclear and the discrepancy
      between subjective and more objective responses underlines the probable
      multifactorial nature of the pathogenesis of this symptom in multiple sclerosis.

PMID- 9619198
TI  - The corticomotor representation of upper limb muscles in writer's cramp and
      changes following botulinum toxin injection.
AB  - Transcranial magnetic stimulation was used to investigate the properties of the
      corticomotor pathway and to map the primary motor cortex projection to hand and
      forearm muscles during a sustained isometric contraction in a group of subjects
      with writer's cramp of varying duration. Corticomotor threshold, motor evoked
      potential amplitude and latency, and silent-period duration were normal on both
      sides in all subjects. The maps of the corticomotor projection were displaced
      relative to normal in all subjects, and in some cases were distorted in shape,
      with extensions of the lateral borders and the emergence of almost discrete
      secondary motor areas. The degree of map distortion and displacement was greatest
      in subjects with long-standing writer's cramp (> 5 years), and was bilateral in
      some cases. Injection of botulinum toxin into affected muscles demonstrated that
      the alterations in map topography were not fixed, and could be temporarily
      reversed during the period when the clinical effects of the injection were
      greatest, with the maps returning to their original positions as the effects of
      the injection wore off. It is concluded from this study that there are slowly
      evolving reorganizational changes in the primary motor cortex in writer's cramp,
      and that these changes may be secondary to altered afferent inputs from both
      clinically affected and unaffected muscles.

PMID- 9619199
TI  - Cold injury to nerves is not due to ischaemia alone.
AB  - The effect of cold on nerve fibre populations may be quite selective. Thus it was
      possible in the present study, with precise timing of a non-freezing cold nerve
      injury, to destroy myelinated fibres, but leave unmyelinated fibres intact. The
      aetiology of this cold-induced selective peripheral nerve pathology remains
      controversial, but recent evidence suggests that ischaemia plays an important
      role. To investigate this matter further, we have sought to determine whether
      ischaemia alone might account for such discrete nerve pathology, in a series of
      non-freezing cold injury paradigms. Compared with previous 'pure' ischaemic
      peripheral nerve models, notable differences were found in the present paradigms
      (early post-ischaemic luxury perfusion and severe nerve pathology), suggesting a
      multifactorial aetiology. Nonetheless a tight correlation was evident, with
      increasing duration of cold injury resulting in a progressively more severe
      reduction in post-cold nerve blood flow. Given these findings, we would propose
      that the pathological basis of non-freezing cold nerve injury is one of
      ischaemia, accelerated and enhanced by direct cold injury.

PMID- 9619200
TI  - Providing a cardiac surgery service.

PMID- 9619201
TI  - Strengthening faith in doctors.

PMID- 9619202
TI  - In the spirit of John Snow: anaesthetists and the public health.
AB  - Patients are likely to be receptive to health promotion advice during elective
      hospital admission. Anaesthetists' knowledge of the physiological effects of
      unhealthy lifestyle gives them a unique insight and allows them to play an
      important role in reinforcing the message.

PMID- 9619203
TI  - Imaging in paranasal sinus disease.
AB  - This article reviews the basic anatomy of the paranasal sinuses and discusses the
      role of imaging in the spectrum of paranasal sinus disease. A separate section on
      facial trauma is included.

PMID- 9619204
TI  - MRCOG. Twin pregnancy.

PMID- 9619205
TI  - Olanzapine.
AB  - Olanzapine is a newly introduced atypical neuroleptic, with a broad receptor
      profile similar to that of clozapine. It is as effective as haloperidol against
      the positive symptoms of schizophrenia, and more effective against negative
      symptoms, with significantly fewer extrapyramidal side-effects. Side-effects
      include somnolence and weight gain. It may show efficacy in treatment-resistant
      schizophrenia.

PMID- 9619206
TI  - Substance misuse and psychosis.

PMID- 9619207
TI  - Substance misuse by the elderly.

PMID- 9619208
TI  - Monday to Wednesday tiredness and thirst.

PMID- 9619209
TI  - Theory of the pulmonary artery catheter.

PMID- 9619210
TI  - Use of opioids in non-cancer pain.
AB  - The use of opioids for chronic pain of non-malignant origin remains
      controversial. However, problems anticipated from experience with animal
      experiments and pain-free abusers seldom cause difficulties when opioids are used
      appropriately to treat pain. With sensible guidelines, and in the context of a
      multidisciplinary pain clinic, opioids may provide the only hope of relief to
      many sufferers of chronic pain.

PMID- 9619211
TI  - Health education: taking it with a pinch of salt.

PMID- 9619212
TI  - Modern approach to the diagnosis of osteomyelitis in children.
AB  - Osteomyelitis in childhood is common and causes serious morbidity. X-rays and
      bone scans are the primary tools of radiological investigation. Other imaging
      techniques, including ultrasound, computed tomography, magnetic resonance imaging
      and white cell scintigraphy have a valuable role in difficult cases.

PMID- 9619213
TI  - Management of a patient with a cut throat.

PMID- 9619214
TI  - Organizing a cardiac surgery service.

PMID- 9619215
TI  - Two hearts beating as one.

PMID- 9619216
TI  - The Marrett drawover apparatus.

PMID- 9619217
TI  - Epidural pethidine: pharmacology and clinical experience.
AB  - Pethidine is an effective epidural opioid for the treatment of acute pain. Its
      use has been well described in Australian and New Zealand practice, particularly
      in the field of obstetric anaesthesia. Reported methods of delivery have included
      bolus injection, continuous infusion and patient-controlled epidural analgesia.
      Areas of application have included treatment of postoperative pain, labour pain
      and intraoperative pain. Because of its intermediate lipid solubility, pethidine
      may have advantages over many other epidural opioids. However, potential for
      accumulation of norpethidine limits its use to relatively short durations of
      treatment.

PMID- 9619218
TI  - Potential intrathecal leakage of solutions injected into the epidural space
      following combined spinal epidural anaesthesia.
AB  - A combined spinal epidural anaesthetic (CSE), by design, produces a deliberate
      multicompartment block across a breached dural membrane. Since the lateral holes
      of the epidural catheter may lie in close proximity to the dural puncture site, a
      bolus solution of drug injected via the epidural catheter has the potential to
      leak through the dural puncture into the subarachnoid space. The aim of this
      study was to determine the incidence of intrathecal leak by performing an
      epidurogram. Fifteen patients undergoing surgery with a CSE anaesthetic using a
      16 gauge Tuohy/26 gauge pencil point needle were studied. Within three hours of
      catheter insertion, 12 ml of contrast (iohexol 300 mg/ml) was injected via the
      epidural catheter under fluoroscopic control with screen recording and exposure
      of lateral and anteroposterior X-ray plates. All films were later reviewed for
      evidence of intrathecal spread. We did not observe any evidence of intrathecal
      spread of contrast. However, caution should be observed during administration of
      an intraoperative bolus dose of analgesic agent via a catheter inserted as part
      of a combined spinal epidural anaesthetic technique, particularly with the use of
      hydrophilic opiods.

PMID- 9619219
TI  - The effect of intraoperative ventilation strategies on perioperative atelectasis.
AB  - Several methods of ventilation have previously been shown to reduce
      intraoperative atelectasis and alveolar to arterial oxygen gradient (A-a DO2) in
      healthy patients. This study was designed to show firstly the relative intra
      operative benefit and secondly if any method had an effect on atelectasis
      postoperatively. Using a factorial design we randomized 24 patients to each of
      the four ventilatory interventions (manual inflations, large tidal volumes, PEEP,
      and pressure control inverse ratio ventilation (IRV)). The A-a DO2 was used as
      the measure of atelectasis and data collected intra- and postoperatively for 24
      hours. The mean pre-induction A-a DO2 was 80 mmHg. This study demonstrated that
      PEEP and IRV were most effective in reducing intraoperative A-a DO2 (P < 0.05
      ANCOVA). Using more than one intervention did not improve the A-a DO2. No method
      had any effect on postoperative A-a DO2.

PMID- 9619220
TI  - The effect of forced air warming on postoperative oxygen consumption and
      temperature in elective orthopaedic surgery.
AB  - Actively warming patients during surgery is considered the best method of
      preventing inadvertent hypothermia. In order to investigate the effect of forced
      air warming on postoperative oxygen consumption, we studied 26 patients
      undergoing orthopaedic surgery using a prospective, randomized trial design. We
      measured oxygen consumption, carbon dioxide production, temperature, thermal
      comfort and pain scores. Apart from intraoperative temperature, there were no
      significant differences in these measurements between the two groups. This study
      demonstrated the gradual heat gain and also the potential for hyperthermia from
      pre- and intraoperative forced air warming. We conclude that forced air warming
      is not necessary for moderate duration non-body-cavity surgery if effective
      preinduction covering of patients and minimal surgical exposure is achieved.

PMID- 9619221
TI  - Haemolysis associated with continuous venovenous renal replacement circuits.
AB  - Extracorporeal circuits can cause haemolysis resulting in an increase in plasma
      free haemoglobin (PFHb). High pressures and clots within the circuit have been
      identified as factors increasing the likelihood of haemolysis. Continuous
      venovenous haemodiafiltration (CVVHD) is associated with high circuit pressures
      as the pump-driven circuit clots over a period of time. PFHb was measured during
      CVVHD to determine if circuit life, maximum circuit pressure or the clotting of
      the haemofilter was associated with evidence of haemolysis. Circuit life up to 50
      hours, circuit pressures or haemofilter clotting had no significant effect on
      PFHb. There was a small rise in PFHb in the circuits lasting beyond 50 hours.
      CVVHD circuits can be run up to 50 hours without concern for haemolysis.

PMID- 9619222
TI  - Brown snakes (Pseudonaja genus): venom yields, prothrombin activator
      neutralization and implications affecting antivenom usage.
AB  - The recent high prevalence of fatal bites by Brown snakes (Pseudonaja genus) has
      led to this study of venom yields from 66 brown snake milkings over 15 months.
      The amount of venom obtained from all species was higher than reported
      previously. Electrophoretic and Western blotting analyses of their venoms showed
      significantly lower avidity of Brown snake antivenom (BS-AV) for the prothrombin
      activator (PA) component (190 kD) than for other venom components, including the
      neurotoxins. The LD50 of P. inframacula has been determined for the first time.
      SDS-PAGE (sodium dodecyl sulphate-polyacrylamide gel electrophoresis) and Western
      blotting studies have shown that the Pseudonaja venoms contained proportionately
      more PA component than venoms of the Taipan (Oxyuranus scutellatus) or the Fierce
      snake (O. microlepidotus). Neutralization of the prothrombin activator of the
      Common Brown snake (P. textilis) (Pt-PA) by BS-AV was found to be time dependent
      and 40% remained unneutralized after 30 minutes incubation. Adult rats
      administered quantities of Pt-PA (IV) died with acute disseminated intravascular
      coagulation. Rats were made resistant to Pt-PA by preheparinization or by
      induction of tolerance to increasing quantities of Pt-PA. There is no evidence
      that Pt-PA has intrinsic toxicity apart from being a procoagulant. The
      improvement of BS-AV by addressing its deficiencies should be canvassed.

PMID- 9619223
TI  - Measuring line-related bacteraemia in intensive care patients.
AB  - All patients with an intravascular device in the intensive care units at Prince
      of Wales and Prince Henry Hospitals between July and September 1995 were followed
      for the development of line-related bacteraemia per 1000 line days. Cases of
      sepsis related to an intravascular device were identified using a case definition
      which incorporated clinical and laboratory parameters. Data were collected
      prospectively for the dates of insertion and removal of devices for 188 lines
      inserted in 69 patients. The majority (90%) of lines had both date of insertion
      and removal documented allowing the calculation of the rate of primary
      bacteraemia over 832 at-risk line days. Multiple concurrent lines were more
      common (88.4%) than single lines, with one central and one or two peripheral
      lines being the most common (42.3%) combination. Five cases of bacteraemia were
      diagnosed clinically and confirmed microbiologically. The incidence density of
      primary bacteraemia was 6.0 per 1000 line days (CI 95% 5.7-6.3).

PMID- 9619224
TI  - Intraoperative transoesophageal echocardiography: impact on adult cardiac
      surgery.
AB  - Although multiple case reports have demonstrated the capability of
      transoesophageal echocardiography (TOE) to detect unsuspected cardiac pathology
      with important therapeutic implications, few studies have examined the effect of
      real-time interpretation of routine TOE on clinical management of a typical
      series of cardiac surgery patients. To assess the impact of intraoperative TOE on
      cardiac surgical management, we conducted a prospective observational study on
      238 consecutive patients undergoing intraoperative TOE during adult cardiac
      surgery. Potentially important new diagnostic information was detected in 39 of
      184 (21%) routine and in 53 of 54 requested TOE examinations, and led directly to
      different surgical procedures in 11 of 184 (6%) routine and in 12 of 54 (22%)
      requested TOE examinations. Our data suggests that intraoperative TOE may be a
      valuable tool in the routine management of adult cardiac surgical patients.

PMID- 9619225
TI  - Australian Incident Monitoring Study in intensive care: local unit review
      meetings and report management.
AB  - The Australian Incident Monitoring Study in the intensive care unit (AIMS-ICU) is
      a national study established through nursing and medical collaboration to
      develop, introduce and evaluate an anonymous voluntary incident reporting system.
      To ensure incident monitoring results in improved patient safety, it is essential
      that reported incidents are followed up regularly. Local unit review meetings are
      an effective forum for discussion and review of reports amongst a wide group of
      practitioners from the intensive care unit (ICU). All staff should be invited to
      participate in order to suggest preventative strategies, report on incident
      follow up and explore national study findings. Ongoing momentum of the project is
      assisted by highlighting its positive contributions to patient care and safety
      via newsletters, poster displays and targeted correspondence. New staff require
      orientation to the reporting system and assurance regarding safety of data. The
      emphasis must focus on the system, not the individual.

PMID- 9619226
TI  - Cardiac arrest associated with sulprostone use during caesarean section.
AB  - Sulprostone, a synthetic prostaglandin with potent uterotonic action, has been
      shown to have a low complication rate in a large series. We present a case in
      which a bolus intravenous injection of sulprostone 30 micrograms was administered
      to treat postpartum haemorrhage during caesarean section. The 38-year-old patient
      with no previous cardiac or smoking history developed complete heart block,
      ventricular fibrillation and subsequent asystole. Cardiopulmonary resuscitation
      was successful after 45 minutes. Post resuscitation there was no myocardial
      infarction and she had complete neurological recovery. We postulate that the
      bolus of sulprostone resulted in possible coronary spasm that resulted in cardiac
      arrest.

PMID- 9619227
TI  - Pneumothorax and pneumomediastinum during colonoscopy.
AB  - A case of bowel perforation during diagnostic colonoscopy is reported. This
      resulted in the sudden appearance of massive subcutaneous emphysema of the neck,
      causing acute upper airway obstruction which necessitated urgent endotracheal
      intubation. Large bilateral pneumothoraces and pneumomediastinum were also
      present.

PMID- 9619228
TI  - Recurrent acute upper airway obstruction after anterior cervical fusion.
AB  - A 67-year-old man presented with cervical myelopathy for which a C3/4 discectomy
      and anterior fusion was performed. Recurrent episodes of acute upper airway
      obstruction necessitated laryngoscopy and endotracheal intubation. Drainage of a
      prevertebral collection of CSF and surgical repair of a dural tear corrected the
      obstructive symptoms. Management of the difficult airway is discussed.

PMID- 9619229
TI  - Anaesthesia for tracheoplasty: case report and review of anaesthesia techniques.
AB  - Congenital tracheal stenosis is an uncommon cause of stridor and can be
      associated with other anomalies. It may present anytime during childhood
      depending on the severity of the lesion. The anaesthetist may be involved in all
      stages of management of this problem; from diagnostic investigations to surgical
      correction. Various methods of tracheoplasty have been described, some requiring
      cardiopulmonary bypass support and others may be carried out with conventional
      ventilatory techniques.

PMID- 9619230
TI  - Adverse local reactions to amethocaine cream--audit and case reports.
AB  - Amethocaine has recently been introduced as a topical local anaesthetic
      preparation. Following sporadic reports of severe local adverse effects, we
      conducted an audit of 372 children attending our hospital for day surgery. We
      conclude that 4% amethocaine cream is a safe and effective topical anaesthetic
      and that the incidence of severe local adverse reactions is rare. We also report
      two of these local reactions, one involving occupational exposure.

PMID- 9619231
TI  - Rhabdomyolysis following severe physical exercise in a patient with
      predisposition to malignant hyperthermia.
AB  - A 21-year-old man suffered from exertional heat stroke with impaired
      consciousness and rhabdomyolysis after strenuous physical exercise. Within two
      weeks the patient recovered completely without any specific therapy. Based on the
      symptoms and laboratory investigations, this episode suggested a moderate form of
      malignant hyperthermia. An in vitro contracture test was performed and a
      predisposition to malignant hyperthermia was diagnosed; other muscular diseases
      were excluded by histological examination. At present, the in vitro contracture
      test is the only method used to determine susceptibility to malignant
      hyperthermia and should be performed when the diagnosis is suggested on clinical
      grounds.

PMID- 9619232
TI  - Central regional anaesthesia in a patient with Klippel-Trenaunay syndrome.
AB  - A 27-year-old female with Klippel-Trenaunay Syndrome presented for reconstructive
      surgery of the deep venous system of the right leg. Contrast enhanced dynamic
      computed tomography was performed to exclude the presence of arteriovenous
      malformation of the lumbosacral spine. A combined spinal-epidural technique
      supplemented with light general anaesthesia was performed. The patient's
      condition was stable throughout the three hours of surgery and postoperative
      analgesia was maintained successfully for three days.

PMID- 9619233
TI  - Convulsive movements with sevoflurane.

PMID- 9619234
TI  - Epileptiform EEG potentials with sevoflurane.

PMID- 9619235
TI  - Cato machine failure.

PMID- 9619236
TI  - ACE inhibitors, colloid infusions and anaesthesia.

PMID- 9619237
TI  - More than he Nintended?

PMID- 9619238
TI  - Bradycardia following intrathecal pethidine.

PMID- 9619239
TI  - Maintaining optimal head positioning for laryngoscopy.

PMID- 9619240
TI  - Blind nasotracheal intubation.

PMID- 9619242
TI  - Does amniotic fluid embolism recur?

PMID- 9619243
TI  - Monitoring nitric oxide.

PMID- 9619244
TI  - Comment on historical airways.

PMID- 9619245
TI  - Should FDA regulate the remarketing, refurbishing, and servicing of used medical
      devices?

PMID- 9619246
TI  - FDA: user comments should be the driving force behind any regulatory approach.

PMID- 9619247
TI  - IAMER: maintain competition in the medical equipment industry.

PMID- 9619248
TI  - HIMA: register independent service organizations and inspect only for cause.

PMID- 9619249
TI  - ECRI: there is no threat to public health.

PMID- 9619250
TI  - An in-house perspective: evaluate costs and benefits of FDA regulation.

PMID- 9619251
TI  - An ISO perspective: implement voluntary programs rather than full regulation.

PMID- 9619252
TI  - The Brooklyn Hospital fire and the quality system regulation.

PMID- 9619253
TI  - A practical technique for assessing electromagnetic interference in the clinical
      setting: ad hoc testing.

PMID- 9619254
TI  - Analysis of training activities of clinical engineering departments in the United
      Kingdom.

PMID- 9619256
TI  - Expressions of accuracy in the evaluation of biomedical instrumentation.
AB  - This review discusses and compares the most common and appropriate expressions
      and representations of accuracy in the evaluation of biomedical instrumentation.
      Instruments used to measure blood pressure illustrate the various expressions of
      accuracy in common use. Accuracy of biomedical instruments can be defined as a
      measure of system error. In system error there is a consistent, systematic bias
      inherent in the method or instrument being tested. Two cases or conditions in
      which accuracy may be determined were identified and analyzed: 1) static or
      single-target conditions, and 2) dynamic or continuum-of-target conditions.
      Expressions of accuracy tested included the mean difference/standard deviation
      (MD/SD) method and the regression analysis (RA) method. In the static, single
      target cases examined, the MD/SD method proved acceptable. In the dynamic,
      continuum-of-targets cases examined, the RA method proved the most accurate and
      useful expression of instrumental accuracy. The MD/SD method could be
      significantly misleading in these dynamic target cases. Since the majority of
      biomedical instruments are used in dynamic or continuum-of-targets situations, RA
      is, generally, the method of choice.

PMID- 9619255
TI  - Variability, reproducibility, and data-collection time of pulmonary bedside
      monitoring.
AB  - Breath-by-breath pulmonary function testing at the bedside is now available both
      with special-purpose stand-alone equipment and with the new generation of
      ventilators. The authors studied the variability of, reproducibility of, and
      ideal length of data collection for nine indices of pulmonary function that may
      be useful for ventilatory management, weaning, and patient comfort. Work of
      breathing (as both J/L and J/min), pressure-time product, rapid shallow breathing
      index, respiratory time fraction, respiratory drive, change in esophageal
      pressure during inspiration, expiratory airway resistance, and dynamic compliance
      were measured in ten normal subjects and in eight patients being weaned from
      mechanical ventilation. All nine indices were reproducible when compared by
      paired t-test with two separate sets of data collected in normal subjects.
      Repeated measures in the normal subjects allowed calculation of 95% confidence
      intervals for the nine variables. There was no statistically significant
      difference between data collections of 5 minutes compared with those of 10 and 15
      minutes. Breath-by-breath variability ranged from a coefficient of variation of
      3% for the shallow breathing index in one patient to 131% for the work of
      breathing in J/min in another. Population variability ranged from values reported
      previously for other pulmonary parameters to nearly double for some parameters.
      The authors conclude that a 5-minute data collection time is sufficient to obtain
      reliable breath-by-breath data at the bedside. While taken together these indices
      may provide clinically useful information, their usefulness individually remains
      to be demonstrated because of their large variability.

PMID- 9619257
TI  - Magnetic field stimulates brain reorganization.

PMID- 9619258
TI  - Bioimpedance measurements: tomographic imaging and body composition.

PMID- 9619259
TI  - FDA recognition of consensus standards in the premarket notification program.
AB  - "The FDA has long advocated the use of standards as a significant contributor to
      safety and effectiveness of medical devices," Center for Devices and Radiological
      Health's (CDRH) Donald E. Marlowe and Philip J. Phillips note in the following
      article, highlighting the latest U.S. Food and Drug Administration (FDA) plans
      for use of standards. They note that the important role standards can play has
      been reinforced as part of FDA reengineering efforts undertaken in anticipation
      of an increased regulatory work-load and declining agency resources. As part of
      its restructuring effort, the FDA announced last spring that it would recognize
      some consensus standards for use in the device approval process. Under the new
      510(k) paradigm--the FDA's proposal to streamline premarket review, which
      includes incorporating the use of standards in the review of 510(k) submissions-
      the FDA will accept proof of compliance with standards as evidence of device
      safety and effectiveness. Manufacturers may submit declarations of conformity to
      standards instead of following the traditional review process. The International
      Electrotechnical Commission (IEC) 60601 series of consensus standards, which
      deals with many safety issues common to electrical medical devices, was the first
      to be chosen for regulatory review. Other standards developed by nationally or
      internationally recognized standards development organizations, such as AAMI, may
      be eligible for use to ensure review requirements. In the following article,
      Marlowe and Phillips describe the FDA's plans to use standards in the device
      review process. The article focuses on the use of standards for medical device
      review, the development of the standards recognition process for reviewing
      devices, and the anticipated benefits of using standards to review devices. One
      important development has been the recent implementation of the FDA Modernization
      Act of 1997 (FDAMA), which advocates the use of standards in the device review
      process. In implementing the legislation, the FDA published in the Federal
      Register a list of standards to which manufacturers may declare conformity. Visit
      AAMI's Web site at www.aami.org/news/fda.standards for a copy of the list and for
      information on nominating other standards for official recognition by the agency.
      The FDA expects that use of standards will benefit the agency and manufacturers
      alike: "We estimate that in time, reliance on declarations of conformity to
      recognized standards could save the agency considerable resources while reducing
      the regulatory obstacles to entry to domestic and international markets," state
      the authors.

PMID- 9619260
TI  - A year later: lessons learned from reengineering.

PMID- 9619261
TI  - Human factors in the health care facility.
AB  - Previous articles in this series have investigated the role of human factors
      engineering (HFE) in the design and development of medical devices and
      instrumentation. This article turns its focus to HFE within health care
      facilities--hospitals, clinics, nursing homes, HMOs, etc. The objective of HFE
      for the device manufacturer is to produce effective and safe systems. The health
      care facility is concerned with maintaining the safety of patients and staff,
      enhancing the cost efficiency of its operations, and controlling liability. Human
      factors engineering can be effective in realizing all of these goals. Proactive
      measures include (1) evaluation of currently employed systems for efficiency and
      error potential, (2) evaluation of systems prior to purchase, (3) evaluation and
      enhancement of facilities, and (4) design and evaluation of procedures.
      Retroactively, HFE participation in accident/incident investigations can carry
      such investigations beyond the placing of blame to determining what made a human
      error possible or even inevitable.

PMID- 9619262
TI  - Diagnostic x-ray fundamentals: the generator.

PMID- 9619263
TI  - New opportunities for the development of cancer immunotherapies.

PMID- 9619264
TI  - Molecular therapy for cancer.

PMID- 9619265
TI  - Dysregulation of apoptosis in cancer.

PMID- 9619266
TI  - Enzymatic activation of prodrugs by prostate-specific antigen: targeted therapy
      for metastatic prostate cancer.

PMID- 9619267
TI  - Length control of human telomeres.

PMID- 9619268
TI  - Telomerase in cancer: diagnostic, prognostic, and therapeutic implications.

PMID- 9619269
TI  - Oligodeoxynucleotide inhibitors of function: mRNA and protein interactions.

PMID- 9619270
TI  - DNA combination therapy to stop tumor growth.

PMID- 9619271
TI  - Integrative pathophysiology of solid tumors: role in detection and treatment.

PMID- 9619272
TI  - Molecular determinants of angiogenesis in cancer metastasis.

PMID- 9619273
TI  - Synthetic methods for implementation of encoded reaction cassettes for rapid
      evaluation of combinatorial libraries of catalysts and substrates.

PMID- 9619274
TI  - Fluorous synthesis: an alternative to organic synthesis and solid phase synthesis
      for the preparation of small organic molecules.

PMID- 9619275
TI  - Control of eukaryotic cell cycle progression by phosphorylation of cyclin
      dependent kinases.

PMID- 9619276
TI  - The roles of Jaks and Stats in cytokine signaling.

PMID- 9619277
TI  - The NF-kappa B activation pathway: its regulation and role in inflammation and
      cell survival.

PMID- 9619278
TI  - Genetic modification of T-cell clones for therapy of human viral and malignant
      diseases.

PMID- 9619279
TI  - Immune recognition of malignancies: relevance to immunotherapy.

PMID- 9619280
TI  - Hereditary gynecologic cancer.

PMID- 9619281
TI  - Molecular biology of gynecologic malignancies.

PMID- 9619282
TI  - Biological therapy for gynecologic malignancies.

PMID- 9619283
TI  - Advances in the treatment of cervical cancer.

PMID- 9619284
TI  - Advances in the radiotherapy of gynecologic malignancies.

PMID- 9619285
TI  - Advances in cytoreductive surgery of gynecologic cancers.

PMID- 9619286
TI  - Chemotherapy of ovarian cancer.

PMID- 9619287
TI  - Role of operative laparoscopy in gynecologic oncology.

PMID- 9619288
TI  - Diagnostic and therapeutic advances in gynecologic oncology: screening for
      gynecologic cancer.
AB  - Endometrial carcinoma is associated with a good prognosis because patients tend
      to present with early disease. Mass screening is therefore unlikely to be of
      benefit. High-risk populations may benefit from screening, but no prospective
      studies have demonstrated a benefit in any population. The most promising
      modality for screening appears to be TVS, and a normal TVS may also preclude the
      need for further evaluation of symptomatic patients. The appropriate use of TVS
      in patients on tamoxifen is currently unknown. Hysteroscopy and endometrial
      biopsy may have a role in the evaluation of symptomatic patients but do not
      appear promising as screening modalities.

PMID- 9619289
TI  - High-dose chemotherapy in gynecologic malignancies.

PMID- 9619290
TI  - Prognostic factors in ovarian cancer.

PMID- 9619291
TI  - Advances in the pathology of gynecologic cancer.

PMID- 9619292
TI  - Modulation of synapsin I gene expression in rat cortical neurons by extracellular
      matrix.
AB  - 1. Neuronal differentiation depends on crosstalk between genetic program and
      environmental cues. In this study we tried to dissect this complex interplay by
      culturing neurons from fetal rat brain cortices in a chemically defined, neuron
      specific, medium and on different substrata, either artificial (poly-D-lysine) or
      natural. 2. Among the extracellular matrix compounds used in this study, two
      (collagen I and fibronectin) allowed only a weak attachment of cortical neurons
      to the substratum, while the others (collagen IV, laminin, and basal lamina from
      Engelbreth-Holm-Swarm sarcoma) allowed both firm attachment and moderate to
      extensive neurite outgrowth from neuronal cell bodies. 3. By using synapsin I
      gene expression as a parameter of neuronal differentiation, we found that neurite
      outgrowth and neuronal differentiation are not linearly linked. Synapsin I gene
      expression, in fact, was maximal in neurons cultured on laminin, while the
      fastest neuritic outgrowth was recorded in cultures on poly-D-lysine. 4. The data
      presented in this paper are consistent with the hypothesis that the extracellular
      matrix plays an active role in modulating the differentiative program of neurons.

PMID- 9619293
TI  - Protein kinase C controls the priming step of regulated exocytosis in adrenal
      chromaffin cells.
AB  - 1. To investigate the mechanism whereby protein kinase C enhances secretory
      function in adrenal chromaffin cells, we examined the effects of 12-O
      tetradecanoylphorbor-13-acetate (TPA) on Ca(2+)-induced catecholamine release
      from digitonin-permeabilized cells, resolving the release into a MgATP-dependent
      priming step and a MgATP-independent Ca(2+)-triggered step. Treatment with TPA
      selectively potentiated the priming activity of MgATP, with little increase in
      the MgATP-independent release. The potentiation by TPA of the MgATP-dependent
      priming was blocked by [Ser25]protein kinase C(19-31), a specific substrate of
      protein kinase C. Go 6976, an inhibitor selective for protein kinase C alpha and
      beta isoforms, also blocked the potentiation by TPA. These results suggest that
      activation of protein kinase C, probably the alpha isoform, potentiates the MgATP
      dependent priming step. 2. The antibody raised against GAP-43, a known substrate
      of protein kinase C, also potentiated the MgATP-dependent priming. The effect of
      TPA and that of the anti-GAP-43 antibody were not additive. Calmodulin, which
      binds to GAP-43 and inhibits its phosphorylation by protein kinase C, abolished
      the effect of TPA. Thus, the present results suggest that protein kinase C
      potentiates MgATP-dependent priming, at least in part, through phosphorylation of
      GAP-43.

PMID- 9619294
TI  - Neurite outgrowth-promoting factors in extracts of denervated chick skeletal
      muscle.
AB  - 1. An extract of denervated skeletal muscle contained activity for promotion of
      neurite outgrowth from telencephalic neurons, as well as that from neurons in the
      spinal cord. A factor responsible for the activity was characterized in cultures
      of dissociated neurons. 2. The factor acted on neurons only when they were
      attached to the surface of culture dishes. Since treatments with proteases and
      lectins reduced the outgrowth-promoting activity, the factor was thought to be a
      glycoprotein. 3. Among the monoclonal antibodies raised against the partially
      purified extract, five antibodies were found to inhibit the activity for spinal
      and telencephalic neurons. The most potent antibody, 4D2a, recognized mainly a 63
      kD protein and other minor proteins in the extract. Although the 63-kD protein
      was confirmed to be chick serum albumin by analysis of amino acid sequence, the
      purified albumin exhibited no activity. 4. From these observations, the factor
      was found to be a glycoprotein recognized by the neutralizing antibody as one of
      the minor components of the extract. This factor exhibits its activity in a
      substrate-bound form but not in a diffusible one.

PMID- 9619295
TI  - Free radicals in rabbit spinal cord ischemia: electron spin resonance
      spectroscopy and correlation with SOD activity.
AB  - 1. In nonanesthetized rabbits temporal occlusion of the abdominal aorta was used
      to induce oxidative stress in the lower part of the body including distal
      segments of the spinal cord. 2. Spinal cord samples were taken from the animals
      exposed to 25-min aortic occlusion (AO) or to occlusion followed by 1- or 2-hr
      reperfusion (AO/R1 or AO/R2, respectively) or from sham-operated animals (C). The
      presence of free radicals (FR) in the spinal cord samples frozen in liquid N2 was
      assessed by ESR spectroscopy without spin trapping. Moreover, superoxide
      dismutase (SOD) activity and conjugated diene (CD) levels were measured in the
      samples. 3. In the AO group FR were detected in the spinal cord regions close to
      the occlusion (lower thoracic and distal segments) along with a decrease in SOD
      activity. The calculated g value (g = 2.0291) indicated that the paramagnetic
      signal recorded might be attributed to superoxide radicals. FR were absent in the
      AO/R1 group. Concurrently, the SOD activity revealed a significant tendency to
      return to the control level. FR appeared again in the AO/R2 group, mostly in the
      upper and middle lumbar regions, along with a decrease in SOD activity. No sample
      from the C group revealed FR. A significant increase in CD levels was observed in
      the thoracolumbar region only in the AO/R2 group. The temporary absence of FR in
      the AO/R1 group suggests activation of defense antioxidant mechanisms (e.g.,
      specific enzymatic systems such as SOD), which might have been exhausted later.
      4. Changes in SOD activity similar to those observed in the thoracolumbar region,
      though less noticeable, occurred in the obviously noncompromised tissue (upper
      cervical region). This points to a kind of generalized response of the animal to
      aortic occlusion. 5. Direct ESR spectroscopy revealed the presence of FR as well
      as their time course in the spinal cord during the early phase of
      ischemia/reperfusion injury and the inverse relationship between FR and SOD
      activity.

PMID- 9619296
TI  - Partial characterization of a novel cardioinhibitory peptide from the brain of
      the snail Helix aspersa.
AB  - 1. We report the isolation of a peptide from the brain of the snail Helix aspersa
      by radioimmunoassay using an antisomatostatin. 2. The sequencing of an
      immunopositive fraction showed the presence of a new tridecapeptide, termed Helix
      cardioinhibitory peptide (HCIP), with the following primary structure: H-Val-Phe
      Gln-Asn-Gln-Phe-Lys-Gly-Ile-Gln-Gly-Arg-Phe-NH2. It is structurally related to
      the Achatina cardioexcitatory peptide (ACEP-1) and the terminal-amino acid
      sequence of HCIP is identical to that of FMRFamide family peptides. 3. The
      synthetic HCIP was tested on heart and neuronal activities and it was found to
      have inhibitory actions not only on the ventricle but also on visceral neurons of
      the central nervous system of Helix. Immunocytochemical investigation indicates
      its presence in visceral and parietal ganglia, in which cells taking part in the
      regulation of the heartbeat have been previously identified.

PMID- 9619297
TI  - Reexamination of opioid stimulation of cGMP formation in cell lines of neuronal
      origin.
AB  - 1. The present study reexamines a previous notion on opioid stimulation of cyclic
      GMP (cGMP) formation and the retraction of the original findings. 2. The effect
      of opioid agonists on cGMP accumulation in two cell lines of neuronal origin was
      measured. The proportion of cGMP stimulation in NG108-15 neuroblastoma x glioma
      hybrid cells resembled the proportion of [Ca2+]in elevation by opioids in this
      culture. The failure of opioids to stimulate cGMP formation in SK-N-SH human
      neuroblastoma coincided with the lack of cGMP stimulation by other Ca2+
      mobilizing agents in these cells. The nitric oxide donor nitroprusside elevated
      cGMP in both cell lines. 3. The implication of the opioid-Ca(2+)-NO-cGMP cellular
      pathway for opioid activity in vivo is discussed.

PMID- 9619298
TI  - Antiamnesic action of cromakalim, a potassium channel opener, in mice treated
      with hypoxia- and cerebral ischemia-type stress stimuli.
AB  - 1. The amnesia induced by various stress stimuli through hypoxia and cerebral
      ischemia was evaluated by the shortening of the response latency in a step
      through task in mice. 2. The hypoxia-induced amnesia was reduced by cromakalim, a
      K+ channel opener (KCO), given 10 min before or immediately after the hypoxic
      treatment. 3. Similarly, the ischemia-induced amnesia was also reduced by
      cromakalim given 30 min before the occlusion. 4. In ischemic-induced amnesic
      mice, pyknotic cells, indicating the condensation of chromatin, were observed
      histochemically at the dentate gyrus granule cells in hippocampal regions 96 hr
      after ischemic treatment. In addition, cromakalim inhibited the induction of
      pyknotic cells. 5. These results suggest that KCOs might produce prophylactically
      neuroprotective effects against hypoxia- and cerebral ischemia-induced amnesia.

PMID- 9619299
TI  - Application of fluorescence microscopy to measure apoptosis in Jurkat T cells
      after treatment with a new investigational anticancer agent (N.C.1213).
AB  - 1. Apoptosis as the mechanism of cell death induced by a new cytotoxic and
      anticancer agent (N.C.1213) was investigated by morphological and biochemical
      criteria in human Jurkat T leukemia cells. 2. The effect of N.C.1213 on the
      survival of Jurkat T, LV-50, H-9, and Molt-3 cells was measured. Jurkat T cells
      exhibited the highest response, with less than 10% of the cells remaining viable
      after exposure to 10 microM N.C.1213 for a 24 hr period. All other cell cultures
      were also affected but to a lesser extent. 3. With the use of a fluorescence
      microscope, several morphological features characteristic of apoptosis such as
      condensed chromatin and apoptotic bodies were identified in Jurkat T cells after
      exposure to N.C.1213 and melphalan. The results indicated that melphalan was more
      cytotoxic than N.C.1213 as shown by the dye exclusion test. However, N.C.1213
      showed a greater apoptotic index than melphalan. The IC50 of N.C.1213 in Jurkat T
      cells was determined to be 3.5 microM. 4. A DNA ladder (fragmentation of DNA into
      multimers of approximately 200 base pairs), which is one characteristic feature
      of apoptosis, was not detected when Jurkat T cells were exposed to N.C.1213.
      Hence it is probable that the key morphological events in apoptosis observed in
      the present experimental conditions precede the internucleosomal cleavage of DNA.

PMID- 9619300
TI  - Endothelin-1 binding to endothelin receptors in the rat anterior pituitary gland:
      interaction in the recognition of endothelin-1 between ETA and ETB receptors.
AB  - 1. 125I-Endothelin (ET)-1 binding to the rat anterior pituitary gland was
      saturable and single, with a Kd of 71 pM and a Bmax of 120 fmol/mg. 2. When 1.0
      microM BQ-123 (ETA antagonist) was added to the incubation buffer, the binding
      parameters were 8.3 pM and 8.0 fmol/mg, whereas 10 nM sarafotoxin S6c (ETB
      agonist) exerted little change in these binding parameters (Kd, 72 pM; Bmax, 110
      fmol/mg). 3. ETB receptor-related compounds such as sarafotoxin S6c, ET-3,
      IRL1620, and BQ-788 competitively inhibited 125I-ET-1 binding, only when 1.0
      microM BQ-123 was present in the incubation buffer. 4. Thus, the ETB receptor is
      capable of binding ET-1 when the ETA receptor is being occupied by BQ-123. A
      collaboration mechanism between the ETA and the ETB receptor may function in the
      recognition of ET-1, a typical "bivalent" ligand.

PMID- 9619301
TI  - Direct and continuous electrochemical measurement of noradrenaline-induced nitric
      oxide production in C6 glioma cells.
AB  - 1. Nitric oxide (NO) production in C6 glioma cells was directly monitored in real
      time by electrochemical detection with a NO-specific biosensor. 2. We present
      here the first direct evidence that noradrenaline elicits long-lasting NO
      production in C6 cells pretreated with lipopolysaccharide and interferon-gamma,
      an effect blocked by NG-monomethyl-L-arginine, a NO synthase inhibitor. 3. This
      direct electrochemical measurement of glia-derived NO should facilitate our
      understanding of the kinetics of glial signaling in glia-glia and glia-neuron
      networks in the brain.

PMID- 9619302
TI  - The diaphragm and respiratory muscles.
AB  - This article describes the functional anatomy of the muscles that contribute to
      the generation of ventilatory pressures. The physiologic principles that guide
      their function are analyzed, and their composition and metabolism are described,
      inasmuch as this affects their adaptation and capacity to face acute and chronic
      loads. Special emphasis is placed on the clinical and laboratory evaluation of
      their function. In addition, the concept of respiratory muscle fatigue is
      developed so the reader can place all these concepts in the context of their
      clinical applications.

PMID- 9619303
TI  - Assessment of diaphragm function.
AB  - Assessment of diaphragm function begins with the physical examination, but
      neither the physical examination nor radiography is sensitive enough to detect
      subtle abnormalities of diaphragm function. Maximal static transdiaphragmatic
      pressure and maximal static inspiratory mouth pressure have been widely used as
      measures of diaphragm and inspiratory muscle strength, respectively. Both are
      useful as rough indications of muscle strength, but, because they are highly
      effort dependent, they should not be relied upon for absolute accuracy. Objective
      measurement of diaphragm function requires phrenic nerve stimulation.

PMID- 9619304
TI  - Imaging evaluation of the diaphragm.
AB  - The diaphragm performs most of the physiologic work of inspiration, and forms an
      anatomic barrier between the thoracic and abdominal cavities. Disorders of the
      diaphragm can be related to impairment of either of these functions, and most
      have radiologic manifestations. Both intrathoracic and intra-abdominal disease
      processes can alter the normal radiologic appearance of the diaphragm.
      Abnormalities are usually first detected on chest radiographs, often incidentally
      in asymptomatic patients, and many require further characterization by other
      imaging studies for definitive diagnosis. Fluoroscopy, CT, and MR imaging are
      frequently the most useful additional studies, whereas ultrasonography, barium
      contrast studies, and liver-spleen scintigraphy are occasionally helpful.
      Selection of the most appropriate radiologic technique in a given clinical
      situation can greatly facilitate the diagnosis of diaphragm abnormalities.

PMID- 9619305
TI  - Surgical anatomy of the diaphragm and the phrenic nerve.
AB  - In this article, the anatomy of the diaphragm and phrenic nerves is discussed,
      together with related surgical implications. Since the major cause of phrenic
      nerve injury is surgery, usually for congenital or acquired heart disease,
      incisions in the diaphragm that do not injure major branches of the phrenic nerve
      are also discussed. Diaphragmatic plication is usually required in infants less
      than 3 months of age, and older children may be managed by ventilatory support if
      electrophysiologic studies document the possibility of return of nerve function.
      In adults with normal pulmonary function, unilateral diaphragmatic paralysis is
      usually asymptomatic.

PMID- 9619306
TI  - Congenital diaphragmatic hernia.
AB  - CDH is a developmental abnormality resulting in a diaphragmatic defect which
      permits abdominal viscera to enter the chest. Most cases occur through the
      posterolateral foramen of Bochdalek. The mortality rate associated with CDH
      remains high due to the presence of associated anomalies, pulmonary hypoplasia,
      and pulmonary hypertension in those with adequate lung parenchyma to initially
      support life. A large number of approaches have been used to manage these
      infants, including delayed surgical repair, pharmacologic treatment of pulmonary
      hypertension, high frequency oscillation, ECMO, and surfactant therapy. New, and
      as yet unproven, innovations such as permissive hypercapnea, fetal surgery, and
      liquid ventilation may provide greater hope in the future for severely affected
      infants. Although most surviving children with CDH do well, a significant
      incidence of gastrointestinal and neurologic morbidity still exists.

PMID- 9619307
TI  - Eventration of the diaphragm.
AB  - Eventration of the diaphragm is a condition where the muscle is permanently
      elevated, but retains its continuity and attachments to the costal margin. It is
      rare, seldom symptomatic, and often requires no treatment. In symptomatic
      patients, plication of the diaphragm may offer relief of the symptoms.

PMID- 9619308
TI  - Diaphragm pacing.
AB  - Diaphragm pacing is an established mode of ventilation for patients with upper
      motor neuron injury and preserved phrenic nerve function. Careful patient
      evaluation with regard to phrenic nerve function, motivation, and adequate
      psychosocial support is paramount for successful pacing. In properly selected
      individuals, full-time continuous bilateral pacing for several years has been
      demonstrated with advantages of increased independence and productivity, fewer
      tracheal tube complications, and improved phonation. Ongoing research in the
      field of diaphragm pacing includes refinements in electrode placement and
      continued testing of totally implantable devices.

PMID- 9619309
TI  - Adult presentation of unusual diaphragmatic hernias.
AB  - The vast majority of diaphragmatic hernias occurring in adults are either
      standard hiatal hernias or those presenting acutely due to traumatic disruption
      of the diaphragm. The remaining small fraction represent unusual cases such as
      congenital hernias (Morgagni or Bochdalek) presenting in adulthood or traumatic
      hernias presenting months to years after the traumatic (or surgical) event. The
      recognition and management of these rare cases are discussed.

PMID- 9619310
TI  - Acute traumatic injury of the diaphragm.
AB  - Acute diaphragmatic injury resulting from penetrating or blunt trauma represents
      a challenging clinical entity. Preoperative diagnosis remains difficult in 50% to
      70% of patients, and a timely diagnosis requires a high index of suspicion. Once
      recognized, the usual aspects of surgical repair are straightforward, such as
      single layer repair using heavy non-absorbable suture via the transabdominal
      approach. However, complex injuries such as parahiatal defects, defects involving
      the diaphragmatic pericardium, diaphragmatic avulsion, and injuries with massive
      tissue loss can test the surgeon's skill and creativity. Prioritization of
      management in patients with multiple significant traumatic injuries demands a
      well-organized approach with availability of highly specialized resources and a
      well-coordinated trauma and critical care team.

PMID- 9619311
TI  - The diaphragm in emphysema.
AB  - Because of hyperinflation, the diaphragm of emphysematous patients operates at a
      disadvantageous position which affects its mechanical arrangement, modifies the
      configuration of its zone of apposition, increases its radius of curvature, and
      decreases its muscle fiber length below optimal configuration. The diaphragm in
      emphysema therefore displays a suboptimal configuration limiting its ability to
      function properly but shows no inherent structural insufficiency, unless its
      contractility is impaired by significant arterial blood gas anomalies or severe
      malnutrition. The demand imposed on the diaphragm in emphysema is increased by
      both hyperinflation and air-flow obstruction. With altered performance of the
      diaphragm and increased demand, force reserve is diminished and diaphragmatic
      fatigue may occur; this imbalance is targeted in some treatment modalities of
      emphysema such as pulmonary rehabilitation programs and lung volume reduction
      surgery.

PMID- 9619312
TI  - Hiatus hernia. The condition.
AB  - Hiatal hernia is a common condition. Many patients are asymptomatic or experience
      symptoms of gastroesophageal reflux. However, with larger hernias, the hernia and
      its incarceration are the issues, and most patients with this condition need
      surgical attention.

PMID- 9619313
TI  - Open repair of hiatus hernia: abdominal approach.
AB  - Open hiatus hernia repair can be accomplished with very low mortality and
      excellent long-term results. The vast majority of hiatus hernias, including those
      with peptic structure, can be repaired transabdominally. The Hill repair, the
      Nissen, and the Collis-Nissen are well-established techniques for repairing a
      hiatus hernia that have stood the test of time and are associated with good long
      term results. The technical aspects of these repairs are discussed in detail
      within this article.

PMID- 9619314
TI  - Open repair of hiatus hernia: thoracic approach.
AB  - Open repair of a hiatal hernia remains an excellent method for correction of
      symptomatic gastroesphageal reflux. This article gives a technical description of
      the performance of the Belsey Mark IV hiatal herniorrhaphy and the uncut Collis
      Nissen repair. A brief description of preoperative evaluation and results is also
      included.

PMID- 9619315
TI  - Tumors of the diaphragm.
AB  - Primary tumors of the diaphragm are rare, and more than half are benign.
      Diaphragmatic tumors arise from mesenchymal tissue because of their mesodermal
      origin, and all varieties of these tumors have been reported. An interesting
      paraphenomenon is hypertrophic osteoarthropathy, most commonly seen in tumors of
      neurogenic origin. In most instances, these tumors are small and can be excised
      with a primary repair anticipated. Secondary involvement of the diaphragm from
      lung cancer is more common, but is rarely associated with a resectable lesion.
      Direct extension from other intra-abdominal or intrathoracic tumors can occur,
      commonly from mesothelioma, lung cancer, and hepatic carcinoma. In some cases, en
      bloc excision of the diaphragm is required, and in many instances diaphragmatic
      replacement is necessary using a variety of thin plastic prostheses, if a wide
      resection is required. Attempts at primary repair under tension, especially on
      the left side, may lead to diaphragmatic rupture and herniation.

PMID- 9619316
TI  - Porous diaphragm syndromes.
AB  - Porous diaphragm syndromes are a group of seemingly disparate clinical symptom
      complexes involving a wide variety of unrelated medical specialties. However,
      they are linked by a common anatomical feature, a defect in the diaphragm. They
      usually present with thoracic symptomatology--pleural effusions, pneumothorax,
      hemothorax, empyema--mediated by this defect. Management of these syndromes
      utilizes principles of thoracic surgical practice including thoracotomy and
      thoracoscopy.

PMID- 9619317
TI  - Metastatic pure papillary thyroid carcinoma presenting as a toxic hot nodule.
AB  - In the majority of cases, carcinoma of the thyroid presents as a cold nodule by
      radioiodine and Tc-99m sodium pertechnetate scintigraphy. Whereas the presence of
      a hot nodule usually implies a benign entity, it does not provide complete
      assurance against thyroid malignancy. Presented is a rare case of metastatic pure
      papillary thyroid carcinoma appearing as a hot nodule on Tc-99m sodium
      pertechnetate and I-123 sodium iodide scintigraphy. The implications of such a
      case, its management, and review of the pertinent literature are discussed.

PMID- 9619318
TI  - Reversible severe lower limb pain during a dipyridamole sestamibi myocardial
      perfusion study: a case report.
AB  - A 68-year-old woman reported acute severe pain in both lower limbs during a
      dipyridamole sestamibi myocardial perfusion scan. The pain was rapidly relieved
      by the administration of intravenous aminophylline. A review of the literature on
      the adverse effects of dipyridamole did not include this symptom.

PMID- 9619319
TI  - New method for detection of a bronchopleural fistula: direct instillation of Tc
      99m DTPA into the pleural space via a thoracostomy tube.
AB  - A 65-year-old man who had undergone a right upper lobectomy for squamous cell
      carcinoma developed a persistent air space in the right superior thorax. Because
      a bronchopleural fistula was suspected, a new technique to demonstrate the
      fistula was used. Five mCi of Tc-99m DTPA was instilled through a pigtail
      catheter into the cavity. Radiotracer activity extended into the remaining right
      bronchial tree, trachea, and left bronchial tree on the 10 minute delayed image
      confirming the presence of a bronchopleural fistula. Using bronchoscopic
      guidance, the fistula was sealed with a fibrin plug. A repeat examination 4 days
      later revealed no extension of tracer from the cavity up to 60 minutes after
      instillation, indicating successful sealing of the fistula. This technique offers
      a rapid, inexpensive, and portable diagnosis of bronchopleural fistula.

PMID- 9619320
TI  - Decreased hippocampal blood flow related to memory impairment after
      cardiovascular surgery: assessment by reconstructed SPECT parallel to the
      longitudinal axis of the hippocampal formations.
AB  - Hippocampal damage has been linked to memory impairment. To clarify the
      relationship between decreased hippocampal blood flow and memory impairment in
      patients after cardiovascular surgery, the authors compared Tc-99m HMPAO SPECT
      findings and Mini Mental State Examination (MMSE) scores. Eight patients who had
      valve replacement, two who underwent aorto-coronary bypass, two who had aortic
      aneurysm replacement and one who had a ventricular septal defect closure were
      included in this study. Cerebral perfusion was estimated using reconstructed
      tomographic images, which were parallel to the longitudinal axis of the
      hippocampal formations. The hippocampal uptake ratios of Tc-99m HMPAO were
      calculated and normalized to that of the cerebellum. In three patients whose MMSE
      score decreased after surgery, the hippocampal uptake ratio was significantly
      reduced (0.69 +/- 0.09) compared with the remaining 10 patients whose MMSE scores
      did not decrease after surgery (0.91 +/- 0.02). These data suggest that SPECT
      imaging parallel to the longitudinal axis of the hippocampus is sensitive to
      decreased hippocampal blood flow, and decreased hippocampal blood flow is related
      to memory impairment in some patients after cardiovascular surgery.

PMID- 9619321
TI  - Diagnosis of pericardial effusion and its effects on ventricular function using
      gated Tc-99m sestamibi perfusion SPECT.
AB  - Pericardial effusion is a common disorder associated with a variety of medical
      disorders. Diagnostic methods of choice include echocardiography, CT, and MRI.
      However, diagnosing pericardial effusion with radionuclides is uncommon. A
      pericardial effusion under pressure may result in tamponade and hemodynamic
      compromise, which constitutes a cardiac emergency, necessitating emergency
      intervention with pericardiocentesis or pericardiotomy. Presented is an unusual
      case of a patient who was referred to the nuclear cardiology laboratory for
      evaluation of atypical chest pain using stress and rest Tc-99m sestamibi
      perfusion SPECT. The patient had a large pericardial effusion evident on planar
      projection images and tomograms. From the gated perfusion study, the authors were
      able to evaluate left and right ventricular function and to exclude cardiac
      tamponade because there was no evidence of diastolic collapse of the right
      ventricle.

PMID- 9619322
TI  - The effects of new platelet inhibitory drug E-5510 on platelet deposition on
      aortic bifurcation grafts: assessment by indium-111-oxime labeled platelet
      imaging.
AB  - The effects of a recently synthesized anti-platelet aggregation drug (E-5510) on
      platelet deposition in a knitted Dacron aortic graft underwent preliminary
      evaluation by In-111 oxime labeled platelet imaging. Seven patients undergoing
      aortofemoral bypass using this graft for occlusive disease were randomized into
      two groups: those receiving E-5510 and those receiving no medication. This agent
      was administered for 17 days postoperatively, and on the 14th day In-111
      platelets were injected and images were acquired at 24, 48, and 72 hours.
      Platelet deposits in the grafts were assessed by the ratios of graft
      radioactivity to that of the adjacent native iliac arteries. Platelet deposition
      at the sites of anastomosis and deposition along the entire graft were normalized
      by initial deposition at 24 hours, and had significantly decreased at 72 hours in
      the three treated patients, while the normalized deposition increased
      progressively over time in the remaining four nonmedicated patients. E-5510 seems
      to have the potential to inhibit excessive platelet deposition on recently
      implanted grafts.

PMID- 9619323
TI  - Splenic hamartoma presenting as a "hot spot" on Tc-99m phytate SPECT imaging.
AB  - The cases of two patients with surgically proven splenic hamartomas with "hot
      spots" on Tc-99m phytate SPECT imaging are presented. There was intense
      radiocolloid accumulation in the peripheral portion of a large single tumor in
      one patient, and in each of three isolated tumors in the other patient. The
      intense uptake might be related to the function of proliferated
      reticuloendothelial cells in the tumors. These unique findings were not clearly
      identified on the planar images.

PMID- 9619324
TI  - Radionuclide imaging in primary amyloidosis with liver involvement.
AB  - A 74-year-old man with hepatomegaly, hyperglycemia, and proteinuria was diagnosed
      with primary amyloidosis with liver involvement, proven by biopsy. Abnormal
      distribution of tracer in the liver on Tc-99m phytate liver-spleen imaging and
      abnormal tracer uptake by the liver on Tc-99m pyrophosphate whole body imaging
      were observed. Scintigraphic imaging studies may be used noninvasively to
      evaluate the involvement of organs in patients with primary amyloidosis, reducing
      the risk of bleeding caused by biopsy.

PMID- 9619325
TI  - Characteristic colonic activity with granulocyte scintigraphy in pseudomembranous
      colitis.

PMID- 9619326
TI  - Radioiodine hot hand sign.

PMID- 9619327
TI  - Progression of neonatal herpes simplex meningoencephalitis demonstrated by
      sequential Tc-99m DTPA brain imaging.

PMID- 9619328
TI  - Fan-beam Tc-99m HMPAO brain SPECT in acute carbon monoxide poisoning.

PMID- 9619329
TI  - Abdominal red blood cell imaging in an infant on total parenteral nutrition
      because of colon agangliosis.

PMID- 9619330
TI  - Bone imaging in advanced gastric cancer.

PMID- 9619332
TI  - Pseudoadrenal uptake of bone imaging agent secondary to focal acute radiation
      nephritis.

PMID- 9619331
TI  - Multiorgan uptake of Tc-99m MDP in a patient with stage 4 alveolar
      rhabdomyosarcoma.

PMID- 9619333
TI  - Tc-99m MDP scan in medullary carcinoma of the thyroid with bone marrow invasion.

PMID- 9619334
TI  - Distinctive patterns of super scan appearance in bone metastasis and
      hyperthyroidism.

PMID- 9619335
TI  - Incidental localization of Baker's cyst with Tc-99m human immunoglobulin.

PMID- 9619336
TI  - Ga-67 imaging of perisplenic abscess after splenic embolization.

PMID- 9619337
TI  - Calcified aortic valve seen on image fusion.

PMID- 9619338
TI  - Tc-99m RBC SPECT showing colonic bleeding in traumatic pseudoaneurysm with
      arteriocolonic fistula.

PMID- 9619339
TI  - 3-D display of Tc-99m DMSA SPECT in crossed fused renal ectopia.

PMID- 9619340
TI  - Selective oestrogen receptor modulators: a new paradigm for HRT.
AB  - Selective oestrogen receptor modulators are a range of compounds which mimic
      some, but not all, agonist actions of oestrogen in different tissues. They were
      developed with the aim of maximizing the benefits of oestrogen-like drugs in a
      number of important conditions whilst reducing adverse side-effects. The
      molecular biology of oestrogen receptor signalling is discussed in relation to
      the pharmacological effects of this class of drugs. The results of clinical trial
      data with one member of this group (raloxifene) are documented and future
      developments outlined.

PMID- 9619342
TI  - Cancer in women with infertility.
AB  - There has been increasing concern in recent years regarding a possible link
      between drugs given for infertility treatment and the subsequent risk of cancer,
      particularly ovarian cancer. Recent epidemiological studies reassure us that any
      effect, if present, is likely to be small, and does not affect women who conceive
      with such treatment.

PMID- 9619341
TI  - New approaches to insulin resistance in polycystic ovarian syndrome.
AB  - The aetiology of the polycystic ovarian syndrome together with new advances in
      the molecular genetics and possible candidate genes for the inheritance of the
      syndrome is discussed. The possible role of leptin in the obesity of polycystic
      ovarian syndrome is reviewed. Hyperinsulinaemia acts not only as the trigger for
      hyperandrogenaemia and infertility, but also by stimulating plasminogen activator
      inhibitor type 1; hyperinsulinaemia may also promote atherogenesis in polycystic
      ovarian syndrome. The long-term effects of the metabolic derangements
      accompanying hyperinsulinaemia are reviewed. Special emphasis is placed on the
      use of novel insulin sensitizers such as troglitazone which promise new treatment
      opportunities in polycystic ovarian syndrome for both fertility and long-term
      disease prevention.

PMID- 9619343
TI  - Oral contraceptives and thrombosis.

PMID- 9619344
TI  - Adolescent contraception.
AB  - Adolescent pregnancy rates have declined modestly, most likely because of the
      increased use of condoms, especially at first intercourse. Condom distribution in
      schools appears to be effective in promoting condom use without increasing sexual
      activity. Although, to date, no contraceptive has been as effective as Norplant
      in reducing teen pregnancy, use of the method has declined dramatically. Depo
      Provera use is increasing, but continuation rates are disappointing and the
      impact on teen pregnancy rates is as yet unknown. Emergency contraception remains
      underutilized, and interventions to improve oral contraceptive compliance are
      beginning to be explored. School-based programs that provide contraception
      without adding a strong educational component fail to improve contraceptive use
      or reduce pregnancy rates. Use of any contraceptive by teens is cost effective.

PMID- 9619345
TI  - Micromanipulation in assisted reproduction: a review of current technology.

PMID- 9619346
TI  - Follicle stimulating hormone as a predictor of fertility.
AB  - Tests for diminished ovarian reserve provide valuable prognostic information for
      women considering assisted reproductive technology. The best characterized
      screening tool for a general infertility patient is the clomiphene citrate
      challenge test. These screening tests do not have absolute sensitivity or
      specificity. Additionally, the predictive value of these tests can be low if used
      in a population at low risk. Patients with abnormal testing should be counselled
      that their chances of conception with assisted reproductive technology are poor.
      This may impact on the choice of aggressive treatment; however, the results of
      these tests should never be used to exclude patients from care.

PMID- 9619347
TI  - The management of hydrosalpinges before in-vitro fertilization and embryo
      transfer.
AB  - Several recent studies have shown that the presence of hydrosalpinges adversely
      affects clinical pregnancy rates achieved with in-vitro fertilization and embryo
      transfer. Hydrosalpinx fluid may be toxic to the endometrium or embryo, or may
      mechanically interfere with implantation. Some authors recommend surgical
      correction of hydrosalpinges before in-vitro fertilization and have shown
      promising results with this approach. Proper patient selection for this therapy
      still needs to be defined.

PMID- 9619349
TI  - Reproductive endocrinology.

PMID- 9619348
TI  - Is there a role for gamete intra-fallopian transfer and other tubal insemination
      procedures?
AB  - In-vitro fertilization pregnancy rates have risen dramatically over the past
      decade. Consequently, fewer patients are currently undergoing gamete intra
      fallopian transfer and zygote intra-fallopian transfer. This review identifies
      which patients may still benefit from tubal transfer procedures. Additionally,
      recent modifications in intrauterine insemination techniques may significantly
      raise pregnancy rates.

PMID- 9619350
TI  - Fertility.

PMID- 9619351
TI  - Complexities, pitfalls, and strategies for evaluating brain tumor therapies.

PMID- 9619352
TI  - Molecular biology of central nervous system tumors.
AB  - Cell growth, cell migration, and angiogenesis are normal biologic processes
      hijacked by tumor cells to promote tumor proliferation, invasion, and
      neovascularity. Great strides have been made in characterizing the altered gene
      expression and acquired genetic mutations in central nervous system tumors. This
      review focuses on the known or implicated genetic alterations and their
      contribution to these biologic processes, with an emphasis on recent
      contributions to the field.

PMID- 9619353
TI  - Pediatric central nervous system tumors.
AB  - Much of the recent change in the management of brain tumors in children has
      centered on the expanded use of chemotherapy. The addition of chemotherapy has
      resulted in better survival rates for children with medulloblastoma and altered
      the management for those with low-grade gliomas. For other tumor types,
      therapeutic advances have been slower. High-dose chemotherapy increasingly is
      being employed to treat malignant childhood tumors, with variable results.

PMID- 9619354
TI  - Advances in brain tumor chemosensitivity.
AB  - Despite advances in surgery and radiation, most malignant central nervous system
      tumours recur. Chemotherapy has assumed an important role in treatment,
      particularly for responsive tumors such as primary central nervous system
      lymphoma and oligodendrogliomas. The design of sound chemotherapeutic trials for
      brain tumors requires an understanding of drug resistance. Drug sensitivity may
      be improved in a variety of ways: through the use of agents at higher than
      conventional doses or in new treatment schedules, through the use of localized
      resistance to modulators, and even through genetic manipulation of malignant
      cells. As treatment with chemotherapy for central nervous system tumors becomes
      more successful, new measurements of tumor response may need to be developed to
      replace or complement standard criteria.

PMID- 9619355
TI  - Locoregional approaches to therapy with gliomas as the paradigm.
AB  - Most malignant gliomas recur locally, despite the fact that these tumors are
      usually found to be diffusely infiltrating on pathologic studies. Thus, efforts
      have concentrated on local disease control as an initial step to improve the
      prognosis of these patients. This review discusses the most recent studies on
      locoregional approaches in therapy for this poor-prognosis neoplasm. Emphasis is
      placed on the radiotherapeutic and combined modality (radiotherapy and
      chemotherapy) approaches reported during the past year.

PMID- 9619356
TI  - Surgical management of local and regional recurrent head and neck squamous cell
      carcinoma.
AB  - During 1997 more than 40,000 Americans developed a squamous cancer of the upper
      aerodigestive tract. Surgery and radiation therapy may have been used alone or
      together, with reasonable prospects for curing them of disease. The majority of
      patients whose cancer cannot be controlled are confronted with local or regional
      recurrence. Such recurrences often occur in sites of the head and neck that are
      suited to early detection during an office examination. Hence, many are treatable
      with curative intent. This review addresses various surgical approaches to these
      difficult management problems.

PMID- 9619357
TI  - Recent randomized trials of chemoradiation in the management of locally advanced
      head and neck cancer.
AB  - The use of concurrent chemotherapy and radiation, or chemoradiation, has become
      the focus of increasing interest in the management of patients with squamous-cell
      head and neck cancer. Randomized trials comparing radiation therapy alone with
      radiation and single chemotherapeutic agents given concurrently have suggested
      benefit for several different drugs. Randomized multiagent chemoradiotherapeutic
      trials have been approached somewhat more tentatively in view of the anticipated
      additional toxicity. Nonetheless, several studies have been reported, and a more
      consistent survival benefit with chemoradiotherapy has been observed. Treatment
      regimens using rapidly alternating chemotherapy and radiation schedules have also
      resulted in an improvement in survival. Although these kinds of aggressive
      treatment approaches produce significant incidences of morbidity and may not be
      appropriate for all patients, a role for chemoradiotherapy in the definitive
      management of this disease is being defined.

PMID- 9619358
TI  - Controversies in the management of locoregionally advanced nasopharyngeal
      carcinoma.
AB  - In patients with locoregionally advanced nasopharyngeal carcinoma the results of
      treatment with conventional radiotherapy are unsatisfactory, with significant
      rates of both distant metastases and local recurrences. The use of neoadjuvant
      and adjuvant chemotherapy has resulted in consistently high response rates, but
      no randomized trial has yet demonstrated an improvement in overall survival.
      Altered-fractionation radiation techniques have not been proven to improve
      survival in locoregionally advanced nasopharyngeal carcinoma, and extreme caution
      is required to minimize unpredicted neurological toxicities. An interim analysis
      of a Head and Neck Intergroup study randomly assigning patients to receive
      concurrent chemotherapy and radiotherapy and adjuvant chemotherapy or
      radiotherapy alone has demonstrated significant benefit in overall survival
      favoring the use of concurrent chemotherapy and radiotherapy. Whether this
      regimen is applicable to all ethnic and histological groups, however, remains to
      be proven.

PMID- 9619359
TI  - Immunotherapy of head and neck cancer.
AB  - Despite advances in surgical chemotherapeutic and radiotherapeutic techniques,
      the overall cure rates for head and neck cancer have been disappointing. There is
      experimental and clinical evidence that deficiencies in the immune system play an
      important role in the initiation and propagation of cancer. Several strategies
      have been investigated to try to correct these deficiencies and also to improve
      the immune response. This article reviews proposed mechanisms of
      immunosuppression, techniques in nonspecific immunotherapy, use of tumor
      infiltrating and cytokine-activated lymphocytes, discoveries and potential uses
      of tumor antigens, and advances in immunogene therapy in head and neck cancer.
      These mechanisms of immunotherapy may become an important modality in the
      treatment of head and neck cancer.

PMID- 9619360
TI  - Update on the taxoids and other new agents in head and neck cancer therapy.
AB  - Both paclitaxel and docetaxel have shown activity when used as a single agent in
      patients with squamous cell carcinoma of the head and neck (SCCHN). Combinations
      of both drugs with platinum derivatives and antimetabolites have been tested in
      patient populations with encouraging results, but some have exhibited
      considerable toxicity. It is unknown as yet whether such combinations are in any
      way superior to the standard platinum-based regimens. Intensive weekly schemes of
      taxoids and platinum compounds alone or in combination seem possible and deserve
      further study. Other agents such as vinorelbine, ifosfamide, thymetaq,
      trimetrexate, gemcitabine and topotecan showed variable activity in patients with
      SCCHN, but their role is still questionable. Following the optimistic view on the
      role of chemoradiation, combinations of paclitaxel (with or without carboplatin)
      with radiotherapy were studied, and the results seem feasible and promising.

PMID- 9619361
TI  - Update on the diagnosis and treatment of prostate cancer.
AB  - Our understanding of the causes of prostate cancer and improvements in screening
      methodologies and risk assessment prior to definitive local therapy continue to
      be refined. The utility of hormone therapy has been further evaluated, both as
      adjuvant and neoadjuvant therapy with radiation therapy or radical prostatectomy,
      as well as for patients with more advanced disease. Finally, modest inroads
      continue to be made in the treatment and understanding of hormone-refractory
      prostate cancer.

PMID- 9619362
TI  - Pediatric genitourinary tumors.
AB  - Each year advances are made in the clinical evaluation and treatment of
      genitourinary tumors in children. Our understanding of cellular, molecular, and
      genetic processes in tumorigenesis is evolving rapidly. In addition, knowledge
      concerning long-term outcome and complications associated with current treatments
      is increasing. In this article, we review recent literature on pediatric
      rhabdomyosarcoma, Wilms' tumor, and testicular tumors.

PMID- 9619363
TI  - Renal cell carcinoma.
AB  - Renal cell carcinoma (RCC) continues to be a frustrating tumor for clinicians to
      manage and treat. Progress has been made in the identification of risk factors,
      particularly dietary risk factors. An increased risk has been seen with frequent
      consumption of fried meat and poultry. Citrus fruits, vitamin C, beta-carotene,
      and alpha-tocopherol have demonstrated a protective effect against RCC. Other
      factors that have been associated with the risk of RCC are smoking (which doubles
      the risk), obesity, hypertension, and exposure to asbestos and petroleum
      products. Response rates for systemic treatment of RCC continue to hover at about
      20%; however, some nonchemotherapy treatments may provide palliation with few
      side effects. In addition, lower dose combinations of interleukin-2 and
      interferon alfa may be as beneficial as higher dose regimens, but with less
      toxicity. Molecular prognostic factors, including proliferation markers,
      karyometric analyses, oncogenes, and cell adhesion molecules and proteases are
      areas of intense investigation and may provide mechanisms for identifying
      patients who require more (or less) aggressive treatment.

PMID- 9619364
TI  - Germ cell cancer of the testis.
AB  - Publications confirming a higher incidence of testicular germ cell cancer (GCC)
      in offspring of dizygous than in monozygous pregnancies and following pregnancies
      associated with severe maternal nausea show that transplacental-acting estrogen
      damage to fetal germ cells is becoming established as a major epidemiologic risk
      factor for these tumors. Endogenous retrovirus expression in GCC is a new
      observation that, given the confirmation that a high-frequency recessive gene was
      the best-fitting genetic model of familial GCC, opens up new areas for
      epidemiologic research. With two papers confirming the importance of excess p53
      expression in determining GCC chemotherapy response, particularly in seminoma,
      the question of whether seminoma should be treated with different chemotherapy
      strategies re-emerges. Preclinical data on oxaloplatin suggest that it is active
      in cisplatin-resistant tumors, and justifies further trials to reduce our
      dependence on cisplatin. These trials will be difficult to undertake given the
      long time taken to prove the poor results from use of carboplatin--which 12 years
      after launch has now been shown to be 17% worse at 3 years in combination with
      bleomycin and etoposide.

PMID- 9619365
TI  - Bladder cancer.
AB  - Identification of genetic alterations in bladder cancer is proceeding very
      rapidly. The most common genetic alteration identified to date in bladder cancer
      is loss of heterozygosity of chromosome 9, suggesting a possible tumor-suppressor
      gene on this chromosome. Because none of the Ta tumors showed loss of
      heterozygosity of 9p, it may be possible to speculate that inactivation of a gene
      located on 9q may be the earlier event. The genes p53 and pRb have been
      associated with disease progression and survival; what is more important is that
      this effect is more pronounced if both markers are altered. One may postulate
      from these results that the loss of the function of wild-type p53 allows cells
      with DNA damage to proceed through the cell cycle, replicating genetic errors.
      Similarly, loss of normal pRb disrupts regulation of cell cycle, and thus
      decreased pRb expression in bladder cancer correlates with increased mitotic
      index. It has been shown that adjuvant chemotherapy affects favorably only those
      patients with p53-altered tumors with regard to decreased risk of recurrence and
      increased survival. Thus, p53 may be useful not only in predicting the aggressive
      nature of the tumor, but also in identifying patients who will not benefit from
      chemotherapy. Significant tumor reduction and a high local control rate were
      clearly demonstrated by a combination of radiation and radiosensitizing agents.
      Although promising survival rates with intact bladders have been reported, only a
      selected group of patients with muscle-invasive disease may benefit from this
      approach. Further studies in molecular genetics surely will enable a more refined
      approach for selecting treatment modalities in bladder cancer.

PMID- 9619366
TI  - Brain and nervous system.

PMID- 9619367
TI  - Head and neck.

PMID- 9619368
TI  - Genitourinary system.

PMID- 9619369
TI  - Expression of active thrombopoietin and identification of its key residues
      responsible for receptor binding.
AB  - In this report expression of the biologically active N-terminal half (amino acids
      1-153) of thrombopoietin (TPO153) in Escherichia coli is described and the
      structure-function relationships in TPO are explored. TPO153 was chosen for
      expression because of its full biological activity. Since natural TPO153 cDNA
      expressed poorly, synthetic cDNA was constructed with a unique polymerase chain
      reaction to enhance the expression. In addition, the 5'-end codons of the
      synthetic cDNA were altered to maximize the expression. The expressed TPO153 was
      refolded and then purified to homogeneity. The protein is biologically active,
      and interestingly, the EC50 of this protein is 8-10-fold smaller in a TPO
      dependent cell proliferation assay than that of full-length wild-type TPO. In
      order to identify the amino acid residues that are involved in the interaction
      between TPO and its receptor, all charged residues and some of the uncharged
      residues on the four putative helices of TPO were mutated and biological
      activities of the mutant proteins were examined. The mutagenesis studies suggest
      that there are at least two clusters of residues that are vital for TPO to be
      able to interact with its receptor. These residues are centred respectively
      around arginine 10 on helix 1 and around lysine 138 on helix IV. The successful
      expression of the protein in E. coli will greatly facilitate biochemical and
      crystallographic studies of TPO, and the structure-function relationship studies
      suggest that TPO has two binding sites which may interact with two individual
      receptors, resulting in dimerization of the receptors.

PMID- 9619370
TI  - Function of the human interleukin 4 receptor (IL-4R)-derived acidic motif
      revealed by cytoplasmic domain chimeras of the IL-4R alpha chain and the IL-2R
      beta chain.
AB  - Interleukin 2 (IL-2)- and IL-4-mediated stimulation of survival and growth,
      reflected by the induction of bcl2 and c-myc, respectively, depends on the
      integrity of the membrane-proximal region (S-region) in the IL-2 receptor beta
      chain (IL-2R beta) and the haematopoietin homology box1-containing region of the
      IL-4 receptor alpha-chain (IL-4R alpha). In contrast to IL-4, IL-2 induces the
      expression of c-fos and c-jun family genes, mediated by the acidic region (A
      region) within the cytoplasmic domain of IL-2R beta. A highly acidic motif is
      also present in IL-4R alpha, and evidence in favour and against its importance
      has been published. The authors have constructed chimeric receptors between IL-2R
      beta and IL-4R alpha by substitution of either the S-region or the A-region of IL
      2R beta with sequences derived from IL-4R alpha. These chimeras were stably
      transfected into BA/F3 cells and assayed for the capacity to restore functions of
      IL-2 beta, such as growth mediation by IL-2 and the induction of proto-oncogenes
      (c-myc, c-junB and c-fos). Replacement of both the S- and A-region of IL-2R beta
      with IL-4R alpha derived regions of similar size and cytoplasmic location
      supported growth-stimulation by IL-2 as well as proto-oncogene induction. In
      contrast, all IL-2R functions were lost by exchange of the S-region with the
      corresponding part of IL-4R alpha. Induction of c-junB and c-fos RNA as an
      indicator of A-region function, however, was maintained in an IL-2R beta chimera
      containing the acidic box-bearing region of IL-4R alpha. These data indicate a
      functional role of the acidic region in the IL-4R alpha-chain.

PMID- 9619371
TI  - Cytokine gene expression in murine fetal intestine: potential for extrathymic T
      cell development.
AB  - An increasing body of evidence suggests that certain T cell subsets mature
      extrathymically in the epithelium of the intestine. In the studies reported here,
      the authors have analysed cytokine/growth factor gene expression, recombinase
      activating gene RAG-1 and RAG-2 gene expression and terminal deoxynucleotidyl
      transferase (TdT) gene expression in mouse fetal intestine and fetal thymus and
      liver, two known haematopoietic tissues. Stem cell factor (SCF) and interleukin 7
      (IL-7) message was abundant in all three tissues during fetal development. IL-2
      and IL-4 were not expressed in fetal gut but IL-4 was weakly detected in fetal
      liver and thymus. IL-9 and IL-13 mRNA was detected in all fetal tissues and IL-15
      mRNA was abundant in fetal intestine but only weakly expressed in fetal liver and
      thymus. mRNA for SCF, IL-7, IL-13 and IL-15 was also detected in fibroblast-like
      cell lines derived from fetal intestine. RAG-1 and RAG-2 mRNA was detected in all
      three fetal tissues. TdT mRNA was not detected in fetal gut or liver but was
      weakly expressed in (fetal day) fd19-20 fetal thymus. Long-term (> 6 weeks) in
      vitro growth of IEL was achieved by coculturing intraepithelial lymphocytes (IEL)
      with IL-7-secreting fibroblasts in the presence of SCF and IL-2. The data show
      that the fetal mouse gut provides a suitable environment for lymphocyte
      development and receptor rearrangement, similar to fetal thymus and liver, even
      though expansion of intestinal IEL is delayed until 2-3 weeks after birth.

PMID- 9619372
TI  - Interleukin 8 and monocyte chemoattractant protein 1 production by cultured human
      airway smooth muscle cells.
AB  - Leukocyte accumulation and activation are key events in the pathogenesis of
      inflammatory lung disease. The ability of human airway smooth muscle cells (HASM)
      to contribute to the inflammatory process by its ability to produce the
      chemokines interleukin (IL) 8, monocyte chemotactic protein (MCP-1) and regulated
      on activation, normal T cell expressed and secreted (RANTES) was investigated.
      Cultured HASM, when stimulated with the pro-inflammatory cytokines IL-1 alpha
      (0.01-1 ng/ml) or tumour necrosis factor alpha (TNF-alpha, 0.3-30 ng/ml),
      synthesize and release substantial amounts of IL-8, as assessed by specific
      immunoassay, bioasssay (elevation of intracellular free calcium in human
      neutrophils), and upregulation of mRNA. These stimuli also increased MCP-1
      production and mRNA expression, but RANTES mRNA expression was not detected at 24
      h. The smooth muscle spasmogen endothelin 1 (1 microM) was unable to stimulate IL
      8 or MCP-1 release or mRNA expression. These data indicate that HASM may
      constitute an important source of leukocyte attractants in the inflamed lung,
      where the inducing stimuli, IL-1 alpha and TNF-alpha, are also likely to be
      present.

PMID- 9619373
TI  - Role of growth factors on extracellular matrix production by chick embryo
      fibroblasts in vitro. Antagonist effect of TGF-beta through the control of IL-1
      and IL-1Ra secretion.
AB  - Growth factors and extracellular matrix (ECM) macromolecules create specific
      environments that regulate cell proliferation and differentiation during
      embryonic development. This study had two main aims: (1) to characterize the
      phenotype of 7- and 13-day-old chick embryo fibroblasts treated with interleukin
      1 (IL-1) and interleukin 6 (IL-6) evaluating in particular the neosynthesis of
      the total proteins and of the fibronectin (FN); (2) to examine the mechanisms
      through which transforming growth factor beta (TGF-beta) antagonizes the action
      of IL-1. The results show that protein neosynthesis and secretion is modulated by
      treatment with IL-1 and IL-6 only in 7-day-old fibroblasts. IL-1 favours cellular
      accumulation, while IL-6 promotes secretion more. FN, isolated by affinity
      chromatography and analysed by SDS-PAGE and flurography, is produced in greater
      concentrations by 7-day-old fibroblasts. Treatment with IL-1 promotes the
      accumulation of FN in the cellular compartment both at 7 and 13 days, while it
      stimulates the secretion only in 7-day-old fibroblasts. IL-6 only has a
      stimulating effect on the processes of accumulation and secretion on 13-day-old
      fibroblasts. The authors show in addition, that TFG-beta blocks the IL-1 induced
      inhibitory effect on glycosaminoglycan (GAG) and collagen production, evaluated
      with [3H]glucosamine and [3H]proline incorporation studies, respectively. The
      effect is evident when TGF-beta is added either before of with the cytokine.
      Analysis in cell culture supernatants, using specific ELISA kit and the study of
      the proliferative responses in mouse thymocytes, showed that TGF-beta induces its
      antagonist effects through a downregulation of IL-1 and/or an upregulation of IL
      1 receptor antagonist protein (IL-1Ra). Considered as a whole the data indicate
      that the ILs and TGF-beta are involved in the physiological age-dependent
      accumulation of ECM and that the balance between the secreted cytokine network
      and IL-1Ra amount, may represent a homeostatic mechanism aimed at controlling
      normal embyrogenesis.

PMID- 9619374
TI  - Regulatory role of interleukin 10 in joint inflammation and cartilage destruction
      in murine streptococcal cell wall (SCW) arthritis. More therapeutic benefit with
      IL-4/IL-10 combination therapy than with IL-10 treatment alone.
AB  - Interleukin 10 (IL-10) and IL-4 are important downregulators of a number of
      macrophage functions. The authors investigated the role of endogenous IL-4 and IL
      10 and the therapeutic effect of addition of these cytokines on joint
      inflammation and cartilage destruction in the early stages of the macrophage
      dependent murine streptococcal cell wall (SCW) arthritis model. It was
      demonstrated that endogenous IL-10, but not IL-4, plays a pivotal role in the
      regulation of SCW arthritis. Blocking endogenous IL-10 with anti-IL-10 antibodies
      resulted in a sustained arthritis with more dense synovial infiltrate as well as
      enhanced cartilage damage. Adding exogenous IL-10 further enlarged the
      suppressive effect of endogenous IL-10. Even more pronounced amelioration was
      found with the combination IL-4/IL-10. This resulted in a reduced swelling and a
      restorative overshoot in chondrocyte proteoglycan synthesis at day 4 (140%).
      Treatment with the combination IL-4/IL-10 not only a marked reduction of tumour
      necrosis factor alpha (TNF-alpha) levels, like IL-10 treatment alone, but also
      the IL-1 beta levels were strongly reduced in the synovium. In conclusion, the
      data is consistent with a dominant role of IL-10 in natural suppression of
      arthritis expression, whereas combined treatment with IL-4 and IL-10 appears to
      be of potential therapeutic value.

PMID- 9619375
TI  - Cytokine release and mitogenic activity in the viridans streptococcal shock
      syndrome.
AB  - Viridans streptococci are a heterogeneous group of Gram-positive bacteria that
      are normal inhabitants of the mouth, upper gastrointestinal tract and oropharynx.
      These organisms are typically thought of as of low virulence, classically as the
      cause of infective endocarditis, although recently they have been implicated in
      serious infections in other settings. In particular, viridans group streptococci
      have been described as responsible for the alpha-streptococcal shock syndrome in
      neutropenic patients. The mechanism by which viridans streptococci cause
      bacteraemia associated with adult respiratory distress syndrome (ARDS) in these
      patients has not been elucidated. Using enzyme-linked immunosorbent assays, we
      compared the ability of cell-free bacterial supernatants derived from commensal
      and clinical strains of viridans streptococci to induce the pro-inflammatory
      cytokines tumour necrosis factor alpha (TNF-alpha), tumour necrosis factor beta
      (TNF-beta) and interleukin 8 (IL-8) from human peripheral blood mononuclear cells
      (PBMC) in vitro. Supernatants of clinical isolates induced significantly more TNF
      beta (P < 0.002) and IL-8 (P < 0.001) than did supernatants from commensal
      strains. The increased production of IL-8 by the clinical strains may be of
      importance in view of the role of IL-8 in the pathogenesis of the acute
      respiratory distress syndrome (ARDS), one of the principal clinical features of
      the alpha-streptococcal shock syndrome.

PMID- 9619376
TI  - Evidence that a fast, rate-sensitive negative feedback effect of corticosterone
      is not a principal mechanism underlying the indomethacin inhibition of
      interleukin-1 beta-induced adrenocorticotropin secretion in the rat.
AB  - A number of previous studies have concluded that prostaglandins (PGs) play a
      crucial role in mediating the corticotropin-releasing hormone and
      adrenocorticotropin (ACTH) secretion induced by interleukin (IL) 1 beta in the
      rat. This is mainly based on a significant inhibitory effect of indomethacin, a
      cyclooxygenase inhibitor, on the hormonal response. However, there is one
      previous study which reported that such an inhibitory action of indomethacin on
      ACTH secretion is mediated principally by a fast, rate-sensitive negative
      feedback effect of corticosterone which increases after indomethacin injection,
      rather than by a decrease in PG production. In order to have a better
      understanding of this unresolved issue, in the present study the authors compared
      the effects of two different time intervals (10 or 20 min) between the
      intravenous injections of indomethacin (10 mg/kg body weight) and of recombinant
      human IL-1 beta (3 micrograms/kg body weight) on the cytokine-induced ACTH
      secretion in male rats. Although IL-1 beta-induced ACTH response was
      significantly suppressed by indomethacin given either 10 or 20 min before, the
      latter protocol led to a significantly greater inhibition of the hormonal
      response than the former. However, between the two groups, the rising slope of
      corticosterone from -20 or -10 min to time zero and that from time zero to 10 min
      after IL-1 beta injection were statistically indistinguishable. There results
      strongly suggest that the fast, rate-sensitive negative feedback effect of
      corticosterone may not be a principal mechanism whereby indomethacin inhibits IL
      1 beta-induced ACTH secretion in the rat. It was concluded that such an action of
      indomethacin is primarily mediated by its inherent pharmacological action, i.e.
      the inhibition of endogenous PG production.

PMID- 9619377
TI  - Mortality and platelet depletion occur independently of fibrinogen consumption in
      murine models of tumour necrosis factor-mediated systemic inflammatory responses.
AB  - Tumour necrosis factor (TNF) is known to have procoagulant activity, and platelet
      depletion is a feature of TNF-mediated systemic inflammatory responses. The aim
      of this study was to investigate the role of fibrinogen consumption in the
      development of TNF-mediated systemic inflammatory responses and in the associated
      depletion of platelets. Three murine models of TNF-mediated systemic inflammatory
      responses were examined: the systemic toxicity reactions (STR) induced by TNF or
      lipopolysaccharide (LPS) and severe malaria (SM), a prominently neurological
      complication of Plasmodium berghei ANKA infection in susceptible mice. There was
      an acceleration in the consumption of fibrinogen during TNF-STR but not during
      LPS-STR or SM. However, a concomitant reduction in platelet count was found in
      all conditions. Mice preliminarily depleted in fibrinogen by treatment with
      ancrod, an enzyme that specifically degrades fibrinogen, showed no protection
      against mortality during TNF- or LPS-STR or SM, although they were protected
      against tissue damage during a modification of the classical local Shwartzman
      reaction. During TNF- and LPS-STR platelets were even lower in ancrod-treated
      than control mice and during SM they were not significantly different. This study
      shows that fibrinogen consumption, although accelerated by the direct injection
      of TNF, is not necessary for the development of TNF-mediated systemic
      inflammatory responses in mice, at variance with local pathology, and does not
      contribute to the associated depletion of platelets.

PMID- 9619378
TI  - Different roles of brain interleukin 1 in the adrenocorticotropin response to
      central versus peripheral administration of lipopolysaccharide in the rat.
AB  - Although it is well established that peripheral administration of endotoxin
      activates the hypothalamic-pituitary-adrenal (HPA) axis, information is very
      limited regarding whether central administration of endotoxin can similarly
      stimulate the endocrine axis. Moreover, it is also unknown whether a difference
      exists in the mode of involvement of brain-derived cytokines in determining the
      HPA response to peripheral vs central administration of endotoxin. In the present
      study, the authors attempted to gain more knowledge on these issues focusing on
      interleukin (IL) 1 in the brain, one of key pro-inflammatory cytokines mediating
      the immuno-endocrine network. In male rats, both intravenous (i.v., 100
      micrograms/kg body weight) and intracerebroventricular [i.c.v. (the 3rd
      ventricle), 10 micrograms] injections of Escherichia coli lipopolysaccharide
      (LPS) caused a significant elevation of adrenocorticotropin (ACTH) levels in
      plasma, even though peaked ACTH responses occurred earlier after the i.v. (60 min
      post-injection) than the i.c.v. (120 min post-injection) LPS. Although the ACTH
      response to i.c.v. LPS was significantly suppressed by a prior (5 min) i.c.v.
      administration of IL-1 receptor antagonist (IL-1Ra, 1 microgram), the hormonal
      response to i.v. LPS was not. That this dose of IL-1Ra was not biologically a
      small dose was indicated by another experiment that the same dose of i.c.v. IL
      1Ra was able to significantly suppress the ACTH response to an i.c.v. injection
      of recombinant human IL-1 beta (50 ng). These results suggest that i.c.v. LPS, as
      i.v. LPS, can stimulate ACTH secretion in the rat, and this hormonal response
      may, at least in part, be mediated by brain-derived IL-1. Although there is one
      previous study reporting an important role of central IL-1 in mediating the HPA
      response to systemic LPS treatment, our present data suggest that such a
      mechanism may not operate before and during an early, peak phase of ACTH
      secretion after i.v. LPS.

PMID- 9619379
TI  - Self-expanding metal oesophageal endoprostheses: which is best?
AB  - Palliation is necessary in over 50% of patients with oesophageal cancer, and the
      most effective means of achieving this is still debated. Plastic or stainless
      steel reinforced endoprostheses have been available for some 20 years, but have
      the disadvantages of bulky introducing systems, a significant incidence of
      perforation and, frequently, sub-optimal palliation. The introduction of self
      expanding metallic stents (SEMS) in 1990 was received enthusiastically on account
      of their relative ease of insertion, with low perforation risk and greater
      internal diameter of 20-25 cm, resulting in better relief of dysphagia. However,
      disadvantages of SEMS include the high cost of the stents and disposable delivery
      systems, the difficulty in removing or repositioning these stents, and the high
      rate of re-intervention because of tumour ingrowth with uncovered stents, stent
      displacement with their covered counterparts, and obstruction owing to stent
      compression or tumour overgrowth at either end of the stent. Published studies
      include a randomized study between conventional plastic prostheses and uncovered
      Wallstents, a non-randomized study comparing uncovered Wallstents and Ultraflex
      stents, and the study published in this issue comparing uncovered Ultraflex
      stents with covered Wallstents. Somewhat surprisingly, 30 day mortality and
      relief of dysphagia were similar between conventional prostheses and uncovered
      Wallstents, and despite a 10-fold increase in cost of the SEMS over plastic
      prostheses, the overall cost of palliation was less because of a mean hospital
      stay of 5.4 days compared with 12.5 days for plastic prostheses, which is higher
      than many reported series and may relate to their insertion under general
      anaesthesia in this study. From the comparative studies of different SEMS,
      uncovered stents are associated with a higher incidence of tumour ingrowth and
      covered stents with a higher incidence of stent migration, particularly when they
      traverse the cardia. Thirty day mortality is relatively high (16-27%), although
      one study found no procedure-related mortality using the uncovered Ultraflex
      stent, but the reintervention rate was uniformly higher with those stents as
      compared with covered or uncovered Wallstents. Improvements in SEMS design are
      likely to overcome many of the technical problems, at which point it would be
      necessary to conduct prospective randomized studies against conventional
      prostheses inserted under sedation, with quality of life and economic assessment
      and sufficient numbers to enable sub-group analysis for variables such as tumour
      site and morphology. In the meantime, specialized centres should have facilities
      for each of the current palliative modalities so as to be able to deploy those
      most suited to individual circumstances.

PMID- 9619380
TI  - Should antibiotic treatment of Helicobacter-positive patients with non-ulcer
      dyspepsia now be recommended?
AB  - Whether cure of Helicobacter pylori infection leads to sustained improvement of
      non-ulcer dyspepsia (NUD) symptoms is one of the most important unresolved
      clinical questions in this area. H. pylori has not helped in explaining
      pathophysiological abnormalities which may cause dyspepsia symptoms. Currently
      there is insufficient evidence from randomized clinical trials to be sure that
      cure of H. pylori infection will improve symptoms. There are potential downsides
      to the widespread use of antibiotics, these include the problem of antibiotic
      resistance and the possibility of less adequate pH control with acid-suppressive
      therapy after the infection has been cured.

PMID- 9619381
TI  - Self-expanding metal oesophageal endoprostheses, covered and uncovered: a review
      of 30 cases.
AB  - OBJECTIVE: Oesophageal self-expanding metal endoprostheses (SEMS, or stents) are
      recognized as a safe means of palliating dysphagia caused by malignancy. Stent
      designs that have covered or uncovered walls are now available. The purpose of
      this study was to compare the outcome of use of these two designs. DESIGN: Thirty
      consecutive cases were reviewed. All the patients had been referred over a period
      of 25 months for palliation of dysphagia caused by malignant obstruction. Either
      a covered or an uncovered stent was placed in each patient. Palliation of
      dysphagia, 30 day mortality, mean survival time, and the number of endoscopic re
      interventions required, were assessed. RESULTS: Uncovered Ultraflex stents were
      used in 14 patients, and Schneider Wallstents were used in 16 patients. Dysphagia
      improved by one grade or more in 69% of patients. The 30 day mortality was 27%,
      with an overall mean survival time of 99 days. There was no significant
      difference between the two groups for these three parameters. Ten patients needed
      a total of 28 repeat endoscopic procedures to maintain stent patency, with
      overall rates for each group of 1.64 procedures per patient, for uncovered
      stents, compared with 0.31 for covered stents (significant at the P < 0.05
      level). The number of repeat procedures increased with survival time. CONCLUSION:
      The use of covered self-expanding metal oesophageal endoprostheses is associated
      with a significant reduction in the need for endoscopic reintervention after
      stent placement.

PMID- 9619382
TI  - A community-based study of the epidemiology of Helicobacter pylori infection and
      associated asymptomatic gastroduodenal pathology.
AB  - OBJECTIVES: To document the epidemiology of Helicobacter pylori infection in a
      normal population, to assess asymptomatic H. pylori positive individuals for the
      presence of gastroduodenal disease, and to compare the macroscopic and
      microscopic findings at endoscopy in this group with those of patients presenting
      with dyspepsia. DESIGN/METHODS: Serum was collected from blood donors and
      assessed for the presence of anti-H. pylori IgG antibodies. A randomly selected
      group of asymptomatic blood donors and dyspeptic patients underwent endoscopy.
      RESULTS: The seroprevalence of H. pylori in 1000 subjects was 43.0%. The
      prevalence of infection increased from 29% in 18-30 year olds to 62% in 46-60
      year olds (P < 0.01). The infection was more prevalent in individuals from social
      classes IV and V (50.0%) than social classes I and II (36.9%) (P < 0.01). There
      was no difference between the H. pylori positive asymptomatic individuals (n =
      37) and matched dyspeptic patients (n = 29) at endoscopy with regard to duodenal
      ulcer (13.5% vs. 17.2%) or gastroduodenal erosions (24.3% vs. 20.7%) while 5.4%
      of the former had gastro-oesophageal reflux compared to 27.6% of the latter.
      Overall, 56.8% of the H. pylori positive asymptomatic group had a normal
      macroscopic endoscopy compared with 31% of the dyspeptic group. Histology of the
      gastric mucosa did not reveal any significant differences between the two groups.
      In H.pylori negative asymptomatic individuals (n = 13) 92.3% had a normal
      endoscopy (7.7% had grade I gastro-oesophageal reflux) compared with 61.5% of a
      matched dyspeptic group (n = 13). CONCLUSION: H.pylori infection, symptomatic and
      asymptomatic, is associated with significant pathology, and screening for the
      infection may be indicated for the prevention of gastroduodenal diseases.

PMID- 9619383
TI  - Helicobacter pylori cagA status, vacA genotypes and ulcer disease.
AB  - OBJECTIVE: Helicobacter pylori is the causative organism of peptic ulcer disease
      and has two putative virulence determinants: the cagA gene which encodes a
      protein of unknown function in 60% of strains, and the vacA gene, which is
      present in all strains, although active cytotoxin is produced in only about 50%
      of these. The relationship between genotypes of both cagA and vacA and resultant
      gastroduodenal pathology is unclear. The objective of this study was to correlate
      vacA genotype and cagA status with gastroduodenal pathology. METHODS: One hundred
      and six dyspeptic patients were studied (average age 56 years, range 19-86 years,
      56 men) referred for routine endoscopy. Macroscopic evidence of gastroduodenal
      disease was noted and antral biopsies taken for culture and genotyping of H.
      pylori. The polymerase chain reaction (PCR) was used to detect the cagA and vacA
      genes of H. pylori using specific primers. RESULTS: Seventy eight of the 106
      (73.6%) patients were cagA positive. Of those who had peptic ulcer disease 29/32
      (90.6%) were cagA positive. The presence of the cagA gene was significantly
      associated with peptic ulcer disease (P = 0.006). The presence of the vacA s1
      genotype was also significantly associated with peptic ulcer disease (P = 0.01).
      The presence of the cagA gene was significantly associated with the vacA s1
      genotype (P < 0.001). There was no significant difference in the distribution of
      the s1/m1 and s1/m2 strains between ulcer and non-ulcer patients. CONCLUSION:
      There is a significant association of the cagA gene and vacA s1 signal sequence
      with gastroduodenal ulcer disease. The relationship of the various other vacA
      genotypes to gastroduodenal ulcer disease is less clear.

PMID- 9619384
TI  - The temporal relationship between oesophageal bile reflux and pH in gastro
      oesophageal reflux disease.
AB  - OBJECTIVE: Damage caused to oesophageal mucosa by bile constituents is pH
      dependent. The aim of this study was to evaluate the relationship between pH and
      duodeno-gastro-oesophageal reflux in gastro-oesophageal reflux disease at night
      in the supine position. DESIGN: A prospective study of 113 patients with reflux
      symptoms [63 without erosive oesophagitis (group 1), 23 with erosive oesophagitis
      (group 2), 27 Barrett's oesophagus (group 3)] and 15 controls. METHODS: All
      subjects underwent 24 h ambulatory oesophageal pH and bilirubin and gastric pH
      monitoring. For the supine period, oesophageal pH during episodes of bile reflux
      was calculated, and the temporal relationship between individual oesophageal and
      gastric alkaline shift and oesophageal bile reflux episodes was established. The
      supine period was divided into four equal segments and the temporal patterns of
      acid and bile reflux and alkaline shift in each of the four supine time segments
      were investigated. RESULTS: Both acid and bile reflux are severe in Barrett's
      oesophagus, particularly at night. Nocturnal oesophageal bile reflux occurs
      mostly between pH 4 and 7 in all groups: 67.6%, 76.5% and 41.4% of the supine
      period for groups 1, 2 and 3 respectively (P < 0.001 vs. pH < 4 or > 7).
      Individual oesophageal bile reflux and oesophageal or gastric alkaline shift
      episodes rarely coincide. Acid reflux predominates in the first half of the night
      (P < 0.001), oesophageal bile reflux and alkaline shift continue throughout the
      night, gastric alkaline shift increases towards the end of the night (P < 0.001).
      CONCLUSION: Duodenal contents in the oesophagus exist at a wide pH range, and may
      have passed through an acid or an alkaline stomach. This has implications for the
      damage which individual constituents are able to cause.

PMID- 9619385
TI  - Direct measurement of post-prandial portal haemodynamics in cirrhotic patients
      with a transjugular intrahepatic portosystemic stent-shunt.
AB  - OBJECTIVE: Portal haemodynamics vary in response to eating and other stimuli, but
      any increase in portal venous pressure (PVP) in cirrhotic patients may be a risk
      factor for variceal bleeding. We directly assessed post-prandial splanchnic
      haemodynamics in cirrhotic patients with a transjugular intrahepatic
      portosystemic stent-shunt (TIPSS) in situ. METHODS: A thermodilution catheter was
      inserted via the patent TIPSS into the portal vein in 12 cirrhotic patients.
      PVP,portal venous flow (PVF) (thermodilution method), portal vascular resistance
      (PVR), porto-atrial pressure gradient (PPG), heart rate, mean arterial pressure
      (MAP) and right atrial pressure (RAP) were measured. A 505 kcal meal was given
      and all haemodynamic measurements were repeated at 15 min intervals for 60 min.
      RESULTS: Following the meal, there was a significant rise in PVP from 11.2 +/-
      1.5 to 14.0 +/- 1.9 mmHg at 15 min, and 14.0 +/- 1.8 mmHg at 30 min (P < 0.001);
      in PPG from 9.5 +/- 1.4 to 12.7 +/- 2.2 mmHg at 15 min and 12.7 +/- 2.1 mmHg at
      30 min (P < 0.005); and in PVF from 1110.2 +/- 141.1 to 1543.2 +/- 227.6 ml/min
      at 30 min (P < 0.01). PVR feil from 0.08 +/- 0.01 to 0.05 +/- 0.01 RU at 30 min
      (P < 0.05). Heart rate increased from 77 +/- 4.1 to 80.5 +/- 5.4 bpm at 15 min (p
      < 0.05), but MAP and RAP remained unchanged. CONCLUSION: In cirrhotic patients
      with TIPSS, significant changes in portal haemodynamics occur at 15-30 min
      following a meal, with minimal effect on systemic haemodynamics. This model
      offers a new technique to directly assess the causes for and possible treatments
      of post-prandial splanchnic hyperaemia in cirrhosis.

PMID- 9619386
TI  - Chronic hepatitis C long-term responders to human leukocyte interferon-alpha
      therapy: persistence of a sustained biochemical and virological response during 5
      years of surveillance.
AB  - OBJECTIVES: To define the biochemical and virological course and IgM response to
      HCV-core protein in long-term responders (LTRs) during a long surveillance (5
      years). DESIGN: From 1989 to 1991, 98 patients (pts) with biopsy-proven chronic
      hepatitis C were enrolled into this study. These pts underwent human leukocyte
      interferon-alpha (LE-IFN alpha) therapy at the prolonged schedule (3 MU thrice
      weekly for 1 year). METHODS: Serum alanine-aminotransferases (ALTs) were assessed
      monthly during and until 1 year after treatment, then every 3 months during the
      observation period. Qualitative and quantitative HCV RNA and HCV IgM were
      measured in all pts on baseline samples and in LTRs also after treatment and
      every following year. RESULTS: Based on serum ALT course, the pts were defined
      as: LTRs (14 pts), if their serum ALT levels returned to the normal range during
      therapy and remained so for at least 1 year afterwards; responders with relapse
      (RRs, 20 pts), if their serum ALT levels returned to the normal range during
      therapy but increased after ending treatment; and non-responders (NRs, 64 pts),
      if their serum ALT levels remained abnormal throughout therapy. No significant
      differences were seen regarding IgM anti-HCV positivity and serum ALT levels
      among the three groups. LTRs (12 HCV-RNA negative and two HCV-RNA positive at the
      end of treatment) maintained their virological status and not one of them
      experienced an elevation of serum ALT levels throughout the surveillance.
      CONCLUSION: Patients affected by chronic hepatitis C and treated with interferon,
      but who did not experience a biochemical or virological relapse within the first
      year of follow-up would not relapse later on; thus, we are able to conclude that
      these subjects made a complete recovery.

PMID- 9619387
TI  - Prognostic and therapeutic score for colorectal adenomas and the role of serum
      and tissue carcinoembryonic antigen.
AB  - OBJECTIVE: To study the tissue carcinoembryonic antigen (TCEA) concentrations
      with regard to multiplicity, diameter, pathohistological finding, degree of
      dysplasia and serum CEA (SCEA) concentrations. METHODS: Our study included 46
      patients with single or multiple adenomas. For 56 adenomas TCEA concentrations
      were measured in addition to standard determinations of multiplicity, diameter,
      pathohistology, degree of dysplasia and SCEA. The measurements of TCEA
      concentrations were performed using the CEA-EIA method (Abbott) modified for wet
      tissue obtained from the head of the adenoma (TCEA-A), margin of resection at the
      neck or base of the adenoma (TCEA-B), mucosa near the adenoma (TCEA-C) and rectal
      mucosa (TCEA-D). The Mann-Whitney test and M estimates were used to differentiate
      CEA distribution between various classes of adenomas within each
      characterization. RESULTS: TCEA concentrations from the head of the adenoma (TCEA
      A) demonstrated highly significant difference between mild and severe dysplasia
      (P = 0.0003), between mild dysplasia and invasive adenocarcinoma (P = 0.001) and
      significant difference between mild and moderate dysplasia (P = 0.04). There was
      a statistically significant difference in TCEA-A also between tubular and villous
      adenomas (P = 0.04). On the other hand, no significant correlations with regard
      to multiplicity, diameter and pathohistological features were found. CONCLUSION:
      These results suggest that there is a highly significant difference between the
      tissue CEA concentration from the head of the adenoma (TCEA-A) in the presence or
      absence of severe dysplasia. Furthermore, combining a number of pathological
      variables together with TCEA and routine SCEA, a new score was proposed to be
      used as a guide to the frequency of follow-up colonoscopy following polypectomy.

PMID- 9619388
TI  - Intravenous cyclosporin as rescue therapy in severe ulcerative colitis: time for
      a reappraisal?
AB  - BACKGROUND: Intravenous cyclosporin is the only new therapy in recent years to
      have made a significant impact on the management of acute severe ulcerative
      colitis (UC). It is increasingly recommended for use in patients who prove
      refractory to the standard regimen of intravenous (i.v.) and rectal
      hydrocortisone but do not warrant immediate surgery. This practice is based on
      uncontrolled and controlled studies which suggest a short-term efficacy of 80%
      and long-term efficacy of 60% in avoiding colectomy. AIM: The aim of this study
      was to assess the short- and long-term efficacy of i.v. cyclosporin in patients
      admitted to our hospital with acute severe ulcerative colitis refractory to i.v.
      steroids, over a 6-year period. METHOD: A retrospective survey of patients
      admitted to the John Radcliffe Hospital, Oxford, with acute severe UC over a 6
      year period (1991-97) was performed. Truelove and Witts criteria for acute severe
      UC were satisfied by 216 patients. RESULTS: The standard regimen achieved
      remission in 132 patients (61%). Of the 84 patients who failed to respond, 34
      (40%) proceeded directly to colectomy whilst 50 received cyclosporin (4 mg/kg by
      continuous slow infusion). Remission was achieved by i.v. cyclosporin in 28/50
      (56%) patients who were subsequently transferred to oral cyclosporin (5 mg/kg).
      However, 8/28 (29%) who initially responded later relapsed after discharge from
      hospital and underwent colectomy. The short-term efficacy of 56% therefore falls
      to 40% in the longer term (mean follow-up of 19 months). CONCLUSION: This is the
      largest survey to date of patients with refractory severe UC treated with i.v.
      cyclosporin. The findings confirm the potential value of i.v. cyclosporin in
      severe UC but its effectiveness in clinical practice is less dramatic than
      previously reported.

PMID- 9619389
TI  - Pain is temporally related to eating but not to defaecation in the irritable
      bowel syndrome (IBS). Patients' description of diarrhea, constipation and symptom
      variation during a prospective 6-week study.
AB  - OBJECTIVES: To study the intensity and variation of pain and its temporal
      relation to eating and defaecation. Furthermore, what irritable bowel (IBS)
      patients mean by constipation and diarrhea and how bowel symptoms vary. DESIGN:
      Prospective daily symptom recording over 6 weeks. SETTING: The primary catchment
      area of University Hospital of Linkoping. PARTICIPANTS: Eighty consecutive
      patients fulfilling the Rome criteria; 63 finished the study. RESULTS: Fifty-nine
      of 63 patients recorded an average of 29 pain periods and 24 days with pain
      during the 6 weeks. Over-all pain burden decreased slightly over the study
      period. At inclusion 38 (64%) patients claimed that pain was relieved by
      defaecation. However, on average, only 10% of each patient's recorded pain
      periods were relieved by defaecation. At inclusion 29 (49%) patients claimed
      postprandial worsening of pain. On average, 50% of each patient's recorded pain
      periods worsened postprandially. The patients defined constipation as hard stools
      and diarrhea as loose stools and urgency. Stool frequency did not differ. Bowel
      symptoms varied within, but not between, fortnightly periods. CONCLUSIONS:
      Postprandial worsening of pain should be included as a criterion in the clinical
      definition of IBS while the criterion 'pain relieved by defaecation' should be re
      evaluated. IBS patients can probably be divided into subgroups based on stool
      consistency, not frequency. Daily records are superior to structured clinical
      interviews or questionnaires for a detailed study of symptoms in IBS.

PMID- 9619390
TI  - Post-ERCP pancreatitis and hyperamylasaemia: the role of operative and patient
      factors.
AB  - BACKGROUND AND AIM: Pancreatitis and hyperamylasaemia are common complications of
      ERCP and this study was designed to explain which operative and patient factors
      predispose to them. PATIENTS AND METHODS: A 1 year prospective study of
      consecutive patients in a single operator centre with detailed attention to
      technical factors and the findings. RESULTS: Four hundred and thirty ERCPs were
      performed. Pancreatitis occurred in 12 cases (2.8%). Amylase results were
      available in 407 cases; 17 were excluded because of pre-operative
      hyperamylasaemia (n = 5) and because of pancreatitis (n = 12). Of the remaining
      390, 30 (7.7%) had hyperamylasaemia. Pancreatitis and hyperamylasaemia usually
      occurred after difficult procedures in which pancreatography was achieved.
      Smaller common bile-ducts, pre-cut papillotomy and some preoperative indications
      also significantly increased the risk of pancreatitis, while prior papillotomy
      was protective. Pancreatitis occurred in patients with a younger median age (52.5
      vs 68.0; P < 0.05) and was more common in women (F:M = 11:1 vs 241:177; P <
      0.05). CONCLUSION: Operative factors are, in part, responsible for the
      development of pancreatitis and hyperamylasaemia but the age and sex of the
      patient also appear to be important.

PMID- 9619391
TI  - Kappa light chain deposition disease of the liver.
AB  - We report the case of a middle-aged woman presenting epigastric discomfort,
      hepatomegaly, biochemical signs of cholestasis, bone marrow plasmocytosis and
      Bence Jones proteinuria. Percutaneous liver biopsy disclosed kappa light chain
      deposition disease of the liver and fine needle aspiration of abdominal fat
      showed amyloid substance. Renal blood chemistries and urinalysis were repeatedly
      normal. To our knowledge, this is the first reported case of kappa light chain
      deposition disease of the liver and concomitant amyloidosis without renal
      involvement as the first manifestation of plasma cell dyscrasia. This condition
      should be considered in the differential diagnosis of intrahepatic cholestatic
      liver disease.

PMID- 9619392
TI  - Crohn's disease presenting as adenocarcinoma of the small bowel.
AB  - Crohn's adenocarcinoma of the small bowel is extremely rare. We report a patient
      with a 10-year history of nonspecific abdominal symptoms who was found on his
      first presentation to have Crohn's adenocarcinoma of the small bowel. Despite
      adequate surgical resection, prognosis for this condition is poor with 2-year
      cancer free survival of around 9%. Crohn's carcinoma should be suspected in
      patients with long-standing disease and those with and without excluded segments
      of bowel.

PMID- 9619393
TI  - Immunosuppressive drug-induced leukoencephalopathy in patients with liver
      transplant.
AB  - Organ transplantation has become a practical and effective option for patients
      with acute and/or chronic irreversible organ disease. However, solid organ
      transplantation is associated with many different complications which depend upon
      the specific surgical procedure and/or confounding medical problems (e.g.
      rejection, infection, adverse effect of immunosuppressive agents) experienced by
      a given patient. Tacrolimus and cyclosporin A are immunosuppressive drugs used to
      prevent rejection following allogeneic solid organ transplantation. Adverse
      events are common with both drugs and include long-term organ dysfunction,
      opportunistic infections, haematopoietic alterations, nephrotoxicity and
      neurotoxicity. Neurological complications, both central and peripheral, occur in
      10-42% of transplant recipients using either of these two immunosuppressive
      agents. Two cases of reversible posterior leukoencephalopathy manifested by
      headache, nausea and seizures associated with the use of immunosuppressive drugs
      following liver transplantation are reported.

PMID- 9619394
TI  - Association between ulcerative colitis and systemic lupus erythematosus: report
      of two cases.
AB  - BACKGROUND: Common aetiopathogenic factors may explain the association of
      ulcerative colitis with autoimmune disorders such as systemic lupus
      erythematosus. PATIENTS: We report two cases of ulcerative colitis associated
      with idiopathic systemic lupus erythematosus: one patient who developed
      ulcerative colitis 11 years after having been diagnosed as a case of systemic
      lupus erythematosus and one case of simultaneous appearance of the two diseases.
      The lupus clinical manifestations were in neither case correlated with the
      treatment of ulcerative colitis. CONCLUSION: The association between ulcerative
      colitis and systemic lupus erythematosus is rare. Although a chance occurrence
      cannot be excluded it is possible that both conditions share some genetic or
      immunological defects.

PMID- 9619395
TI  - IMGT (ImMunoGeneTics) locus on focus. A new section of Experimental and Clinical
      Immunogenetics.
AB  - IMGT, the international ImMunoGeneTics database (http:/(/)imgt.cnusc.fr:8104) is
      an integrated database specialising in immunoglobulins (Ig), T-cell receptors
      (TcR) and major histocompatibility complex (MHC) of all vertebrate species,
      created by Marie-Paule Lefranc, CNRS, Montpellier II University, Montpellier,
      France (lefranc@ligm.crbm.cnrs-mop.fr). IMGT includes three databases: LIGM-DB
      for Ig and TcR, MHC/HLA-DB, and PRIMER-DB (the last two in development). The new
      section of Experimental and Clinical Immunogenetics, 'IMGT locus on focus', will
      give the more updated and extensive overview of the current status of the
      different Ig, TcR and MHC genes in IMGT, with standardization of gene
      nomenclature, functionality, and allele polymorphism according to the IMGT rules
      and unique numbering.

PMID- 9619396
TI  - The human immunoglobulin lambda variable (IGLV) genes and joining (IGLJ)
      segments.
AB  - The first report of the 'IMGT Locus on Focus' section comprises five tables
      entitled: (1) 'Number of human germline IGLV genes at 22q11.1-q11.2 and potential
      repertoire'; (2) 'Human germline IGLV gene table'; (3) 'Human IGLV allele table',
      (4) 'Human germline IGLJ table' and (5) 'Human IGLJ allele table'. These tables
      are available at the MariePaule page from IMGT, the international ImMunoGeneTics
      database (http:/(/)imgt.cnusc.fr:8104) created by Marie-Paule Lefranc, CNRS,
      Universite Montpellier II, Montpellier, France.

PMID- 9619397
TI  - The immunogenic properties of melanoma-associated antigens recognized by
      cytotoxic T lymphocytes.
AB  - During the last 6 years significant progress has been achieved in the
      identification of melanoma-associated antigens recognized by cytotoxic T
      lymphocytes. These antigens belong the three main groups: tumor-associated testis
      specific antigens (MAGE, BAGE, GAGE and PRAME), melanocyte differentiation
      antigens (tyrosinase, Melan-A/MART-1, gp100, TRP-1 and TRP-2) and mutated or
      aberrantly expressed antigens (MUM-1, CDK4, beta-catenin, gp100-in4, p15 and N
      acetylglucosaminyltransferase V). In this review, we have summarized the
      available data concerning the characterization of melanoma-associated antigens
      with focus on their immunogenic and protective properties. The development of a
      strong immune response against differentiation antigens is limited by the
      existence of tolerance against these 'self' antigens, permitting the involvement
      of only T cells with low affinity T cell receptors. Among the melanoma
      differentiation antigens, only gp100 has been shown to be a tumor regression
      antigen. The testis-specific antigens such as MAGE and PRAME should potentially
      be highly immunogenic antigens. They contain several potential HLA class I
      binding epitopes and are present only in the testes which are not accessible to
      the cells of the immune system due to the lack of direct contact with the immune
      cells and the lack of HLA class I expression on the surface of germ cells. But
      only 2 patients have been found who responded to these antigens in vivo,
      indicating their genuinely low immunogenicity. A comparison of the predicted
      secondary structures of these two groups of antigens (testis-specific and
      differentiation antigens) revealed enrichment of long alpha-helical stretches in
      the testis-specific antigens. We hypothesize that such highly organized
      structures could diminish the efficiency of the protein unfolding--a necessary
      step in the proteolytic cleavage by proteasomes--and, therefore, could be
      responsible for the low immunogenicity of these proteins. In this case,
      modifications decreasing the stability of these proteins might be a means to
      improve the immune response against these potentially therapeutically useful
      antigens.

PMID- 9619398
TI  - DQA1*Arg52,DQB1*nonAsp57, and DRB1*04 genotypes in Chinese children with insulin
      dependent diabetes mellitus.
AB  - Ethnic comparisons are extremely important and useful for studying the HLA
      component involved in insulin-dependent diabetes mellitus (IDDM) predisposition.
      To date there have been only a few reports on the association of HLA loci and
      IDDM in Chinese. We report here a study on DQA1*Arg52, DQB1*nonAsp57, and DRB1*04
      in IDDM children and control adults among Han Chinese living in Taiwan. One
      hundred and fourteen unrelated children (62 boys) with IDDM were studied. Their
      ages at diagnosis were between 0.3 and 15.0 years (6.8 +/- 3.6 years). The
      control population consisted of 120 randomly selected normal adults.
      DQA1*Arg52(+/+), DQB1*nonAsp57(+/+), and DRB1*04(+/-) were associated with IDDM
      (RR = 11.50, 2.21, and 2.82; p = 1.11 x 10(-15), 2.84 x 10(-3), and 1.98 x 10(
      4), respectively). DQA1*Arg52, DQB1*nonAsp57, and DRB1*04 conferred risks for
      IDDM (RR = 12.79, 7.11, and 2.83; pc = 8.22 x 10(-4), 5.35 x 10(-3), and 5.68 x
      10(-4), respectively). Combinations of DQA1*Arg52 and DRB1*04 conferred the
      highest risk for IDDM (RR = 19.64, pc = 5.4 x 10(-5)). DQA1*Arg52 was associated
      with IDDM in subjects with DQB1*nonAsp57+ (RR = 14.87, pc = 2.41 x 10(-4)) and
      DQB1*nonAsp57 was also associated with IDDM in subjects with DQA1*Arg52+ (RR =
      8.41, pc = 1.54 x 10(-3)), suggesting that DQA1*Arg52 and DQB1*nonAsp57 are
      interacting. This study demonstrates that DQA1*Arg52, DQB1*nonAsp57, and DRB1*04
      confer susceptibility for IDDM to Chinese children. A combination of DQA1*Arg52
      and DRB1*04 confers the highest risk and it is suggested that a susceptibility
      gene might be situated between DQA1*Arg52 and DRB1*04 or both are synergistic.
      There is an interaction between DQA1*Arg52 and DQB1*nonAsp57 and homozygosity for
      DQA1*Arg52/DQB1*nonAsp57, which encodes four susceptibility DQ heterodimers,
      confers a high risk.

PMID- 9619400
TI  - BoLA DYA polymorphism in Czech cattle.
AB  - Polymorphism at the BoLA DYA locus was determined in two groups of Czech Black
      Pied cattle by PCR-RFLP detecting substitutions at nucleotide positions 112 and
      219. Animals for this study were nonrandomly selected according to their health
      status in two BoLA-associated infections: bovine leukosis (n = 59) and Johne's
      disease (n = 36). A group of noninfected Czech Red Pied cows (n = 37) was used
      for comparison. The frequencies of DYA alleles and haplotypes were virtually
      identical in the two selected groups as well as in the infection-free animals. In
      contrast, distribution of BoLA DRB3.2 alleles differed considerably between the
      infected groups as expected based on the previously detected associations with
      BoLA. The results suggest that the polymorphism of the DYA unexpressed gene was
      not influenced by selecting animals for this study according to their health
      status.

PMID- 9619399
TI  - Gluten stimulation induces an in vitro expansion of peripheral blood T gamma
      delta cells from HLA-DQ2-positive subjects of families of patients with celiac
      disease.
AB  - The intestinal gluten sensitivity formally known as celiac disease (CD) is
      characterized by an evident involvement of local immune response and it is
      associated with the expression of HLA-DQ2 allele. The major role in the disease
      seems to be played by the T lymphocyte population bearing gamma delta T cell
      receptor (T gamma delta cells) which are increased both in peripheral blood and
      intestinal mucosae of celiac patients. In this paper data on the effects of in
      vitro gluten stimulation on lymphocytes expressing the T gamma delta phenotype
      are reported. Gluten seems to be able to induce the expansion of the T gamma
      delta cell population both in CD patients and their HLA-DQ2-positive asymptomatic
      relatives, in spite of the absence of clinical evidence of the disease. In
      addition, the evaluation of gluten-induced cytokine production shows that
      interleukin-4 could be implied in the early phases of pathogenesis of CD.

PMID- 9619401
TI  - [The characteristics of the development of the immune function in the
      transplanted spleen of newborn mouse pups in recipients of different ages. 2. The
      effect of the thymus on the functional development of the transplant].
AB  - The effect of the neonatal thymus grafting or "Thymostimulin" administration on
      the cellularity, cell composition, immune, response to SRBC and proliferative
      activity of T- and B-cells in vitro were determined in neonatal spleen grafted
      CBA/Ca female mice of different ages. Analysis of the thymus graft effect on the
      T- and B-cells content in the spleen transplant from the adult and old recipients
      demonstrated no differences. The neonatal thymus grafting led to the essential
      increase of the immune response, spleen cellularity and to the diametrically
      opposed changing from negative to positive of the sign of the correlation
      coefficient between the T-cells content and the cellularity of the neonatal
      spleen in the old recipients. The similar effect of the neonatal thymus grafting
      was revealed in respect of correlative connection between content of the T-cells
      and PFCs in spleen grafted to the old recipients too. The "Thymostimulin"
      injection led only to the increase of the spleen transplant cellularity. These
      results suggests that the young thymic microenvironment is essential for the
      normal T-cells differentiation and for its normal function in the neonatal spleen
      transplant.

PMID- 9619402
TI  - [The effect of antibodies on the Ca2+ release from the sarcoplasmic reticulum of
      the papillary muscle of the rat heart].
AB  - In experiments of skinned with saponin papillary muscles (PM) of the rat's heart
      we studied the effects of antibodies (AB), which are specific for the
      sarcoplasmic reticulum's membranes (SPR). AB (1-5 mg protein/ml) have been
      established to enhance the amplitude of the isometric PM tension. Inhibition of
      the Ca2+ release from SPR and its previous release prevented the development of
      the exciting effect of AB. Thus, AB increase the amplitude of PM contraction due
      to their intracellular mobilizing action.

PMID- 9619403
TI  - [Natural antileptospirosis immunity in donor-capable subjects].
AB  - Natural antileptospirosis immunity of blood giving capable population of Kyiv was
      studied in 853 persons. It has been ascertained that during a year natural
      antileptospirosis antibodies can be found out in blood serum of people with
      different by ABO system blood groups. Antileptospirosis antibodies of high titres
      (> 1:80) are mostly present in spring and autumn.

PMID- 9619404
TI  - [The effect of hyperbaric oxygenation on liver energy metabolism in white rats
      with acute sodium nitrate poisoning].
AB  - The experimental study carried out on white rats, which was introduced of sodium
      nitrate at a dose of 9,6 g/kg of their mass. It is followed by the development of
      considerable disturbances of energy metabolism in liver. It has been shown the
      depression and the uncoupling of oxidation and phosphorylation, decrease of
      energy quotient in hepatic tissues. The results obtained permit supposing the
      significant role of nitric oxide (NO) in liver as a factor resulting in decrease
      of energy potential. The research has stated that the use of hyperbaric
      oxygenation (HBO) prevents difficult disturbances of energy metabolism in liver
      of white rats. The results permit supposing that the effect HBO is connected with
      the decrease of the speed of reduction of nitrate-ions to more toxic products of
      their biotransformation.

PMID- 9619405
TI  - [Mitochondrial respiration and oxidative phosphorylation in the kidneys of white
      rats under conditions of hemic hypoxia and the use of different suture
      materials].
AB  - The activity of processes of mitochondrial respiration and oxidative
      phosphorylation has been studied in the experiment with white rats, which had
      been carried out nephrotomy with following use for suture such absorbable
      surgical threads as catgut plain biofil (of dura mater spinalis of the cattle)
      and biofil modified with succinate. The research proves the use of catgut plain
      decreases of biosynthetic processes and effectiveness of oxidative
      phosphorylation in 7 and 14 days of postoperative period shown more distinctively
      in condition of blood loss. The use of biofil modified with succinate results in
      the significant increase of oxidative phosphorylation in the sutured renal
      tissue. Following thing can be interred the investigation of influence of
      absorbable suture materials in metabolic processes in sutured tissues in
      condition of modelling of pathological processes, in particular of hypoxia,
      reflects the biological qualities of studied threads more distinctively, kidneys.

PMID- 9619406
TI  - [The effect of hypoxia on the erythrocyte catecholamine depot].
AB  - In experiments on 45 white rats in which the acute hypoxia was caused it has been
      stated that in both cases size and quantity of catecholamine inserts in
      erythroplasma have been decreased, erythrocyte destruction being present. The
      catecholamine loss by erythrocytes was more expressive than by plasma. Besides
      the adrenaline-noradrenaline ratio in erythrocytes changes in the direction of
      adrenaline growth. It takes place due to the hypoxia when carbon dioxide and
      energy change disorders occur, energy deficiency state is developing, which in
      its turn affects the erythrocyte catecholamine depot function.

PMID- 9619407
TI  - [The time characteristics of the brain stem and cortical auditory evoked
      potentials in patients with chronic functional voice disorders].
AB  - The study of time characteristics of short-latency acoustic evoked potentials
      (SLAEP) and long-latency acoustic evoked potentials (LLAEP) in relation to
      electroencephalography (EEG) data was performed in individuals with normal voice
      and hearing, as well as in patients with chronic functional voice impairments
      (CFVI). Significant abnormalities in SLAEP and LLAEP parameters, especially in
      patients with CFVI with low amplitude alpha-rhythm, were revealed. The conducted
      study of SLAEP and LLAEP with respect to EEG data in patients with CFVI with low
      amplitude alpha-rhythm provide objective evidence for beliefs of many clinicians
      about a prominent role of neurogenic factors in the development of functional
      voice impairments as well as the existence of correlation between hearing and
      voice-producing systems. Delay in the sound information processing at the level
      of the brainstem was found in patients with CFVI, especially in those having low
      amplitude alpha-rhythm, which was being observed in prolongation of the latency
      periods of peaks III, IV and V of the SLAEP waves along with widening of the
      interpeak intervals I-III and I-V. Such the patients are characterized by severe
      course of their disease and frequent relapses. The data received could be
      expediently used for treatment and rehabilitation of patients with CFVI and
      solving matters of labor expertise.

PMID- 9619408
TI  - [Functional-structural changes in the myocardium in systemic physical loading].
AB  - By means of ultrastructural and morphometrical methods hearts of 15 white rats
      have been studied during adaptation to the physical static load. This exercise
      induced the adaptive changes of the myocardium: hypertrophy and dilatation of the
      heart chambers. Hypertrophy of the myocardial parts takes place mainly at the
      expense of increasing of the length and width of cardiomyocytes. In these
      structures the increase of synthetic and secretive function was founded. Moderate
      training have improved the metabolism of the cardiomyocytes and created certain
      reserve of energy in the structures which were connected with the process of
      adaptation after the physical static load.

PMID- 9619410
TI  - [Lipid peroxidation in lead-strontium poisoning and its correction with
      flamikar].
AB  - Using the model systems of Pb-Sr intoxication on the white rats was found out,
      that incorporated Pb and Sr had influenced on the activity of lipoperoxidation in
      tissue of rat's internal organs. The intensification of the activity of
      lipoperoxidation was observed in liver, heart, spleen, less in kidneys after five
      days Pb-Sr intoxication. Twenty-days Pb-Sr intoxication was accompanied the
      depression of the activity of lipoperoxidation in liver, heart, kidneys; the
      activity of lipoperoxidation's activation was continued in spleen. Using
      phlamicare--polyextract of mountain ash, is resulted in normalisation of
      lipoperoxidation in rat's internal organs during Pb-Sr intoxication and
      contributed to removing of incorporated Pb and Sr.

PMID- 9619409
TI  - [Dissociation between the development of myocardial contracture and heart damage
      in the "calcium paradox"].
AB  - The interrelationship between contracture development and heart damage during the
      calcium paradox under different sodium concentration in Ca-free media was studied
      on isolated rat hearts. It had been shown that calcium paradox development
      accompanied contracture development, intensive membrane disruption and alteration
      of tissue energy state. We had not found relation between contracture magnitude
      and degree of myocardial alterations in calcium paradox. Our dates confirm so
      called intracellular hypothesis of calcium paradox. The experiments had shown
      close correlation between transmembrane sodium gradient in Ca-free media and
      degree of cellular damage and energy state alterations during calcium readmission
      in solution.

PMID- 9619411
TI  - [Changes in the total calcium content and in the activity of alkaline phosphatase
      and gamma-glutamyltransferase in the blood serum of rats with Monckeberg's
      experimental arteriosclerosis].
AB  - Experiments on rats (single-action, six-days' hyperepinephrinemia and
      monoiodacetatic acid intoxication) were performed to study the calcium
      concentration, alkaline phosphatase and gamma-glutamyltransferase activities in
      serum at Monckeberg's medial calcific sclerosis modelment. It is established
      reduction serum level of calcium in an hour past single-acting
      hyperepinephrinemia, increase it's level after six-days'-monoiodacetatic
      intoxication, increase of "serum alkaline phosphatase activity/gamma
      glutamyltransferase activity" (as indirect evidences the bone isozyme of alkaline
      phosphatase and parathyroid hormone activity increase) after six-days'
      hyperepinephrinemia and monoiodacetatic acid intoxication. Probably, these
      changes in serum calcium metabolism and system it's regulation may play
      pathogenetic role in early period Monckeberg's arteriosclerosogenesis.

PMID- 9619412
TI  - [An evaluation of the action of new nutritional compounds with a radioprotective
      use on the body's immune state].
AB  - Examination of radiosafety effect of the new nutrition compositions were carried
      out in the experiments. The immunomodifying influence of this products were
      established. It is shown the possibility of their addition to the ration of
      population from the polluted territory.

PMID- 9619413
TI  - [Age-related changes in the biorhythms of the mental activity of operating
      personnel].
AB  - There were analysed changes of circadian, circannual and decasecond biorhythms of
      the test tasks' performance of the control room operators in power stations for
      the age diapason 22-53 years. The decasecond rhythms' significance of the mental
      activity rate gradually increases with ageing. The circadian and circannual
      rhythms' significance for indices of attention and activity rate is minimum in
      the middle age group and it is maximum in the senior one. The circadian and
      circannual rhythms' significance for the logic-combinatorial task performance
      quality is maximum in the middle age group. The revealed differences have been
      connected with effect of the professional activity specificity on age changes of
      middle levels of different indices of the operators' mental activity. The complex
      analysis' results of the biorhythms' significance for the different indices of
      mental activity are proposed as a (prognostic) criterion of the operators'
      adjustment to the effective performance of the industrial activity at different
      times of day and year.

PMID- 9619414
TI  - [The effect of meteorological factors on the mental state of virtually healthy
      students].

PMID- 9619415
TI  - [The dynamics of the formation of the properties of the main nervous processes in
      children 4-7 years old].
AB  - Dynamics of formation of characteristics of the main nervous processes
      (functional mobility and power), their connection with the results of mental
      activity of children under school age and the level of their preschool readiness
      have been studied. It has been shown that neurodynamic processes develop
      progressively within a period from four to seven years of age. Mental ability of
      children under school age is substantially determined by characteristics of the
      main nervous processes. Children with better results of their mental ability to
      work and preschool readiness have more significant functional mobility and power
      of nervous processes.

PMID- 9619416
TI  - [Endothelin and the cardiovascular system].
AB  - Endothelin (ET) is a peptide synthetized by endothelial cells (EC), smooth-muscle
      cells (SMC), cardiomyocytes and endocardial cells in response to the effects of
      mechanical factors and some biologically active substances--angiotensin 11,
      interleykin-1, the transforming growth factor-alpha and tumor necrosis factor
      alpha(TNF-alpha). ET possesses significant constrictor action on vessels (100
      times more than angiotensin), positive inotropic action on the heart and
      stimulates proliferation. Increase of the endogenous endothelin concentration has
      been shown in many pathological states of the cardiovascular system. By
      inhibiting ET receptors it has been proved EN involvement in the pathogenesis of
      some of these states--systemic hypertension, myocardial infarction, vasospasm and
      cardiac failure.

PMID- 9619417
TI  - [Enkephalins as regulators of physiological functions].
AB  - The problem of the regulation of the different physiological functions by
      enkephalines is discussed. A cite as an example the data about the regulatory
      action of the enkephalines on the secretory function of the stomach, pancreas and
      liver are discussed. The mechanisms of the enkephalines action on the secretory
      processes are discussed too.

PMID- 9619418
TI  - Cytochrome P450 aromatase in male germ cells.
AB  - The ability of the male gonad to convert androgens into estrogens is well known;
      the microsomal enzymatic complex involved in this transformation is named
      aromatase and is composed of a specific cytochrome P450 aromatase (P450arom) and
      an ubiquitous reductase. According to age, aromatase activity has been already
      measured in immature and mature rat Leydig cells as well as in Sertoli cells.
      Recently, in different studies, a cytochrome P450arom has even been
      immunolocalized not only in Leydig cells but also in germ cells of mouse, brown
      bear and rooster whereas in pig, ram and human the aromatase is mainly present in
      Leydig cells. Our purpose was to investigate the testicular cell distribution of
      cytochrome P450arom mRNA in adult rat using RT-PCR. With two highly specific
      primers located on exons 8 and 9, we have been able to amplify a 289 bp aromatase
      fragment not only in Leydig cells and Sertoli cells but also in highly-enriched
      preparations of pachytene spermatocytes, round spermatids and testicular
      spermatozoa. These amplified products showed 100% homology with the corresponding
      fragment of the rat ovary cDNA. In parallel, using an anti-human cytochrome
      P450arom antibody we have demonstrated the presence of a 55 kDa protein in
      seminiferous tubules and crude germ cells (pachytene spermatocytes and round
      spermatids) of the mature rat. After incubation with tritiated androstenedione,
      the aromatase activity in the microsomal fractions of purified testicular
      spermatozoa was 2.96 pmoles/mg/h and was found to be 5-fold higher when compared
      to that of either purified pachytene spermatocytes or round spermatids. Using a
      quantitative RT-PCR method with a standard cDNA 29 bp shorter, we have compared
      the amount of cytochrome P450arom mRNA in mature rat Leydig cells and Sertoli
      cells. In purified Leydig cells from mature rats the P450arom mRNA level was: 36
      x 10(-3) amoles/microgram RNA whereas in Sertoli cells the mRNA level was 10 fold
      lower. In pachytene spermatocytes, round spermatids and testicular spermatozoa
      the P450arom mRNA levels were respectively 367, 117 and < 1 x 10(-3)
      amoles/microgram RNA. Therefore, we evidenced that not only the Leydig cells but
      also the Sertoli cells of the rat during the testicular maturation have the
      capacity to express the gene of the cytochrome P450 aromatase. More importantly a
      biologically active cytochrome P450 aromatase is also present in germ cells
      (pachytene spermatocytes, round spermatids and spermatozoa). The existence of an
      additional source of estrogens within the genital tract of the male is now well
      documented and that suggests a putative role for these hormones during the male
      germ cell development and maturation not only in the testis but also in the
      epididymis.

PMID- 9619419
TI  - The use of congo red as a lyotropic liquid crystal to carry stains in a model
      immunotargeting system--microscopic studies.
AB  - The lyotropic liquid crystal dye-Congo Red was used as a carrier in a model
      immunotargeting system constructed from sheep red blood cells (SRBC) representing
      the antigen target and rabbit IgG anti-SRBC as the specific driving
      immunoglobulin. Rhodamine B and Hemin stains were chosen as example chemicals
      carried to the target. The carried stains were introduced to the micellar
      organization of Congo Red by intercalation. Preserving its supramolecular
      organization, Congo Red binds spontaneously and selectively to antibodies that
      have altered structure extorted by interaction with the antigen in the immune
      complex. The functionality of the studied immunotargeting model was verified by
      fluorescence and electron microscopy. The results indicate that the
      supramolecular nature of protein ligands offers new ligation capabilities
      possibly useful for carrying stains or drugs in immune-oriented systems.

PMID- 9619420
TI  - An inhibitor of the chymotrypsin-like activity of the proteasome (PSI) induces
      similar morphological changes in various cell lines.
AB  - Different established cell lines (SK-v human keratinocytes, B16F10 mouse
      melanoma, Muntjac fibroblasts, 3T3 mouse fibroblasts, CLV human fibroblasts) as
      well as primary cultures of mouse fibroblasts and giant cells were treated with N
      benzyloxycarbonyl-Ile-Glu(O-t-butyl)-Ala-leucinal (proteasome inhibitor, PSI), a
      specific inhibitor of the chymotrypsin-like activity of the proteasome. PSI
      induced well characterized morphological changes in all cell lines studied,
      including vacuolization and accumulation of perinuclear aggregates, as detected
      by amido black staining. Together with previous reports on HeLa cells, the
      present findings support the hypothesis that ubiquitin- and proteasome-dependent
      proteolysis does not occur randomly in the entire cell, but it is concentrated in
      a well defined perinuclear region, the proteolytic center.

PMID- 9619421
TI  - Differences in the inhibition of neuritic outgrowth in organotypic cultures of
      rat foetal dorsal root ganglia treated with cisplatin and carboplatin: a
      comparative study.
AB  - Neurotoxic effect of cisplatin and carboplatin, two anticancer drugs with
      different neurotoxic potential, was examined in organotypic cultures of rat
      foetal dorsal root ganglia (DRG), maintained in a semisolid agar culture medium.
      Two main parameters of neurites growing out of the ganglia--the mean radial
      length of neurites and the area of neurite outgrowth--were used to evaluate the
      toxic influence of both drugs. IC50 values were calculated from the dose-response
      curves established at three cultivation time points (24, 48, and 72 h). Cisplatin
      demonstrated higher toxicity in comparison with carboplatin for all exposure
      times. The lowest concentration which caused neurite outgrowth alteration was 25
      microM of carboplatin and 10 microM of cisplatin. IC 50 was 11.93, 8.25, 8.58
      microM for cisplatin and 177.46, 47.83, 44.94 for carboplatin after 24, 48 and 72
      h, respectively.

PMID- 9619422
TI  - Microtubules are responsible for the asymmetrical distribution of organelles in
      the oocytes of the hymenopteran, Chrysis ignita.
AB  - Previous morphological investigations have shown that the distribution of
      cellular organelles and reserve materials in hymenopteran oocytes is uneven and
      often gradient-like. It has been suggested that the microtubular cytoskeleton is
      responsible for creating and/or maintaining the distribution gradients. To test
      this hypothesis, adult females of the hymenopteran, Chrysis ignita were treated
      with a microtubule-assemble inhibitor, colchicine. The experiment resulted in a
      number of abnormalities observed in the egg chambers: the oocytes were devoid of
      organelle-free periplasm and oosome; cellular organelles and reserve materials
      were distributed randomly within the oocyte; nurse cells organization was
      significantly changed. These observations have confirmed a key role of
      microtubules in forming and/or maintaining the asymmetry of ooplasm in Chrysis
      ignita.

PMID- 9619423
TI  - Extract from maturing antheridia of Chara induces increased condensation of
      mitotic chromosomes in root meristem cells.
AB  - Serving as the incubation medium for root meristems of Allium cepa and Melandrium
      noctiflorum, crude extracts obtained from maturing male sex organs of Chara
      tomentosa induce: (1) increased condensation (with both shortening and
      thickening) of prophase, metaphase and anaphase chromosomes, (2) disarrangement
      of metaphase plates and aberrant segregation of chromosomes during anaphase, and
      (3) abnormal decondensation of chromosomes at telophase. Numerous resemblances
      that exist between the natural processes occurring in male sex organs of Chara
      and root meristem cells from antheridial extract-treated seedlings suggest the
      existence of a diffusible condensation-promoting factor, responsible for the
      reorganization of chromatin.

PMID- 9619425
TI  - Porous polyglycolide.
AB  - The solid-state polymerization of halogenoacetates leads quantitatively to
      polyglycolide (polyglycolic acid) and an eliminated metal halide. Washing out
      this salt leaves highly porous polyglycolide (total pore volume about 50%) with
      pore sizes in the submicron range. Thorough examination of the product with
      different methods (DSC, IR, and X-ray diffraction) gave no indication of any
      remaining halogenoacetate. This distinct micromorphology should be advantageous
      for its application as a biomaterial. Special features of porous polyglycolide
      are an inherent surface roughness, a high specific surface, a higher gas
      permeability, and a lower density compared to conventionally prepared
      polyglycolide. The control over these properties should allow a fine-tuning of
      the biocompatibility of polyglycolide.

PMID- 9619424
TI  - Effect of calcium on RNA content in meristematic cells of pea (Pisum sativum L.)
      roots treated with toxic metals.
AB  - RNA content in nucleolus, nucleus and cytoplasm in meristematic cells of pea
      roots growing for 144 h in the presence of calcium and/or toxic metals (Cd2+,
      Cr3+, Pb2+) was examined using cytophotometric procedures, after staining with
      gallocyanine. The effect of treatment with tested metals was twofold: on the one
      hand, it considerably reduced RNA content in the nucleolus, on the other it
      enhanced RNA level in the nucleus and most visibly in the cytoplasm, resulting in
      the increase in total amount of RNA in cells of pea roots. The presence of
      calcium in metal solutions in different ways affected RNA content in meristematic
      cells of pea. In roots treated with cadmium, the addition of calcium ions
      diminished the toxic effect of that metal, as demonstrated by an increase in RNA
      content in the nucleolus, although reduction of RNA amount in the nucleus,
      cytoplasm and in whole cell was observed. A clearly stimulative effect of calcium
      was noted in material grown in the presence of chromium or lead, where a high
      increase in RNA content in nucleolus, nucleus and cytoplasm took place.

PMID- 9619426
TI  - Attachment of gelatin films to tissue using argon beam coagulator.
AB  - Cross-linked gelatin films were bonded to heart muscle and to lung pleura and
      parenchyma using the electrical discharge of an argon beam radiofrequency
      coagulator. The bonds were stable in warm saline buffer for minutes to hours.
      Bonding was thought to partly occur through a mechanical interlock of film and
      tissue elements. The interdigitation of tissue and film arose during exposure to
      the argon beam, which denatured protein constituents of both, and created a
      fluidized state that rapidly coalesced.

PMID- 9619427
TI  - Biocompatibility response to modified Baerveldt glaucoma drains.
AB  - Glaucoma implants are designed to increase fluid outflow from the eye in order to
      decrease intraocular pressure and prevent damage to the optic nerve. The implant
      consists of a silicone tube that is inserted into the anterior chamber at one end
      and is attached at the other end to a silicone plate that is sutured to the
      outside of the globe beneath the conjunctiva. The glaucoma "implant" becomes a
      "drain" over the first 3 to 6 postoperative weeks as the silicone plate is
      enclosed by a fibrous capsule that allows a space to form into which fluid can
      drain and from which fluid can be absorbed by the surrounding tissues. Ideally,
      the size and thickness of the capsule (the filtering bleb) that surrounds the
      plate is such that the amount of fluid that passes through the capsule is
      identical to the amount of fluid produced by the eye at an intraocular pressure
      of 8 to 14 mmHg. The most common long-term complication of these implants is
      failure of the filtering bleb 2 to 4 years after surgery due to the formation of
      a thick fibrous capsule around the device. Micromovement of the smooth drainage
      plate against the scleral surface may be integral to the mechanism of glaucoma
      implant failure by stimulating low-level activation of the wound healing
      response, increased collagen scar formation, and increased fibrous capsule
      thickness. To test this hypothesis, we modified seven Baerveldt implants by
      adding porous cellular ingrowth material to the posterior surface of the drainage
      plate. Seven modified and five unmodified implants were placed in adult rabbit
      eyes. After 6 months, we found that the fibrous capsule around the modified
      implants was significantly thinner than the capsule surrounding the unmodified
      implants (p < 0.05), particularly on the surface between the porous ingrowth
      material and the sclera (p < 0.05). Although type I collagen predominated in the
      fibrous capsules around both types of implants, the amount of type III collagen
      in the capsules around the modified implants was significantly less than the
      amount around the unmodified implants (p < 0.05). We believe that these data
      suggest a reduction in the wound healing response to the modified implants, with
      greater stability of capsule thickness. Long-term studies are needed to verify
      that the stability of the capsules around the modified implants persists over a
      period of years, in which case this type of modification may prove useful in
      prolonging the functional life of these devices in the surgical treatment of
      glaucoma.

PMID- 9619428
TI  - Influence of irrigation solutions on oscillating bone saw blade performance.
AB  - The influence of irrigation on bone cutting was determined by measuring the
      biomechanical performance of a bone cutting saw during irrigation with various
      solutions. Solutions of 0.9% saline and 10, 20, and 30% poloxamer-188 were used
      as the irrigant. A 10% solution of poloxamer-188 was judged to be the superior
      irrigant because it successfully maintained bone temperature at a controlled
      level without interfering with the rate of bone removal.

PMID- 9619429
TI  - Tensile tests of interface between bone and plasma-sprayed HA coating-titanium
      implant.
AB  - Tensile strength testing of the interface between bone and a plasma-sprayed
      hydroxyapatite (HA) coating-Ti-6Al-4V (implant I) and an HA coating-Ti (implant
      II) was performed. The bone-implant interface and tensile failure mode were
      evaluated by light microscopy (LM), SEM-energy dispersive X-ray analysis, and
      backscattered electron imaging. The crystallinity of the HA coating of implant I
      and implant II was 62 and 40%, respectively. Eleven semidisk implants of each
      type were inserted in the left tibia of 22 rabbits in each period. After 2, 4, 8,
      and 16 weeks, the tensile strength of the bone-implant I was 0.86, 1.32, 1.10,
      and 0.92 MPa, respectively; the value of the bone-implant II was 0.66, 0.92,
      0.84, and 1.12 MPa, respectively. No significant difference was found in tensile
      strength between implant I and implant II, and between the data of different
      periods. LM and SEM revealed that the two types of coatings behave the same in
      bone. Failure after the tensile test mainly occurred at the bony tissue at 2 and
      4 weeks, inside the HA coating layer at 8 weeks, and at the HA coating-metal
      substrate interface at 16 weeks. Degradation and delamination of the HA coating
      continued with time, resulting in the interfacial tensile strength not increasing
      with time. Thus, we concluded that differences between the two implants, mainly
      the difference in crystallinity of the HA coating (62 vs. 40%), have no
      significant influence on bone bonding ability, bone bonding strength, tensile
      failure mode, and degradation of the coating.

PMID- 9619431
TI  - Application of long chain amine activator in conventional acrylic bone cement.
AB  - A long chain acid derivative bearing an aromatic tertiary amine group, 4-N,N
      dimethylaminobenzyl laurate (DML), which acts as an activator for the curing of
      acrylic cements at low temperature, has been synthesized and characterized to
      reduce the biological adverse effects usually associated with the classical
      activator N,N-dimethyl-4-toluidine (DMT). The effectiveness of the activator was
      tested on commercial formulations (e.g., Palacos R) and on experimental bone
      cements based on poly (methyl methacrylate) by using different benzoyl
      peroxide/amine molar ratios. The exotherms of polymerization were followed at
      three different temperatures: 25, 30, and 37 degrees C. The DML activator was
      found to be more sensitive to temperature than the corresponding DMT. DML
      provided exotherms of polymerization with decreasing peak temperatures and
      increasing setting times without impairing the mechanical properties. Residual
      monomer content was analyzed in a range of activator concentrations by keeping
      the benzoyl peroxide concentration constant. In all cases the residual monomer
      content was lower than 5%, indicating its good efficiency in the benzoyl peroxide
      initiated polymerization.

PMID- 9619430
TI  - Effects of polyethylene particles on tissue surrounding knee arthroplasties in
      rabbits.
AB  - Clinical studies suggest a role for polyethylene (PE) wear debris in the
      pathogenesis of osteolysis and loosening of total joint replacements. In this
      study, submicron particles of ultrahigh molecular weight PE (UHMWPE) were placed
      around pressfit tibial hemiarthroplasties in rabbits to determine the biological
      reaction. After 6 months the periprosthetic tissue was harvested and
      characterized biochemically by measuring the extracellular matrix macromolecules,
      collagen, and glycosaminoglycan (GAG) and quantifying the expression of
      inflammatory/osteolytic mediators [prostaglandin E2 (PGE2), hexosaminidase,
      transforming growth factor beta (TGF beta), and interleukins-6 and -1 (IL-6, IL
      1)]. Particle exposure resulted in a decrease in levels of total extracellular
      matrix molecules including a 53% decrease in total GAG (p < 0.05) and a 74%
      decrease in total collagen (p < 0.005). Collagen content remained significantly
      decreased when normalized for cellularity (DNA content). Total TGF beta release
      exhibited a downward trend (p = 0.06) in the particle exposed group.
      Hexosaminidase and PGE2 levels did not show a difference between groups; however,
      when normalized for cellularity, PGE2 values exhibited an upward trend in the
      particle exposed group (p = 0.1). IL-6 was undetected by bioassay and ELISA.
      Previous studies emphasized that PE debris enhances the degradation of bone. The
      data from this in vivo model suggest that submicron UHMWPE particles may also act
      to inhibit biosynthetic pathways of bone and mesenchymal tissue. Decreased levels
      of collagen, GAG, and TGF beta expression may indicate suppression of bone
      formation, possibly through a downregulation of osteoblast activity.

PMID- 9619432
TI  - Effect of polymerization reaction inhibitor on mechanical properties and surface
      reactivity of bioactive bone cement.
AB  - We introduced an inhibitor to the polymerization reaction of bioactive bone
      cement (AWC) consisting of MgO-CaO-SiO2-P2O5-CaF2 apatite and wollastonite
      containing glass-ceramic powder and bisphenol-alpha-glycidyl methacrylate based
      resin, together with an increased amount of accelerator but without any
      prolongation of its setting time in order to improve the degree of polymerization
      and decrease the amount of incompletely polymerized monomers on the cement
      surface. A comparison was made between the AWC containing the inhibitor [AWC(I+)]
      and the AWC without it [AWC(I-)] with regard to setting parameters, mechanical
      properties, and surface reactivity in vitro and in vivo. The proportion of glass
      ceramic powder added to the AWC was 70% (w/w). The total amount of heat
      generation and the peak temperature of the AWC(I+) during polymerization were
      slightly greater than those of the AWC(I-). The mechanical strength of AWC(I+)
      was higher than that of the AWC(I-) under wet conditions. In simulated body
      fluid, the width of the Ca-P rich layer on the surface of the AWC(I+) was less
      than that on the AWC(I-) after 28 days of immersion, although the rate of apatite
      formation on the top surface of the AWC(I+) was almost identical to that on the
      AWC(I-) surface. Histological examination using rat tibiae up to 26 weeks
      revealed that the bioactivity of the AWC(I+) was equivalent to that of the AWC(I
      ). Scanning electron microscopy and energy-dispersive X-ray microanalysis
      demonstrated that the Ca-P rich layer in the AWC(I+) was significantly narrower
      than that in the AWC(I-) at the same time points. These results indicate that
      introduction of the inhibitor improved the mechanical properties of the AWC and
      made the Ca-P rich layer narrower, but it had no adverse effect on bioactivity.

PMID- 9619433
TI  - Interfacial properties of self-reinforced composite poly(methyl methacrylate).
AB  - Total joint prostheses are often fixed in the bone using bone cement. The cement
      mantle, however, is prone to fatigue fracture that can lead to failure of the
      mantle, evolution of bone cement particles, and eventual loosening and failure of
      the prosthesis. A new material, self-reinforced composite poly(methyl
      methacrylate) (SRC-PMMA) was developed previously by the authors. This material
      has a similar chemical composition to bone cement, with the matrix and
      reinforcing fibers both fabricated from PMMA. One potential use for this material
      is as a precoat for hip prostheses or other stemmed prostheses. This study sought
      to examine the strength of the bonds that SRC-PMMA forms with simulated
      prostheses and bone cement. SRC-PMMA was woven about Co-Cr rods and push out
      tests were performed. Samples were tested in air as processed or after immersion
      in saline for 30 days at 37 degrees C. Three different weaves were investigated
      and compared to bone cement. Bone cement and SRC-PMMA formed interfacial bonds
      with Co-Cr rods that failed at an average load (stress) of 980 N (2.0 MPa). After
      saline immersion, the bone cement's interfacial bond strength was 642 N (1.23
      MPa) and the tight weave SRC-PMMA was statistically stronger at 973 N (1.86 MPa).
      The shear strength within bone cement alone as measured by push out tests was an
      order of magnitude higher at 9210 N (15.2 MPa) in air and 9900 N (15.7 MPa) after
      saline immersion. The bond between SRC-PMMA and bone cement was 10,900 N (17.9
      MPa) in air and 9610 N (15.8 MPa) after immersion in saline. Woven SRC-PMMA
      performed as well or better than bone cement in these push out tests.

PMID- 9619434
TI  - Enhanced bone regeneration and formation around implants using guided bone
      regeneration.
AB  - This study investigated the use of a prototype expanded polytetrafluoroethylene
      membrane attached to bone with butyl-cyanoacrylate, in facilitating guided bone
      regeneration into bone defects and around titanium screws in rabbit femora. Two
      experimental models were used to assess bone growth. The first model investigated
      two unicortical defects in each femora. The second was bone growth in a 500
      micron engineered space around one transcortical titanium screw. In the first
      model there was a significant increase in bone formation at 1 and 2 months in the
      membrane groups (p < 0.01) as compared to the controls. In the second model the
      percentage of bone in contact with the implant was significant at 1 and 2 months
      in the defects covered with membrane compared to the uncovered defects. The
      uncovered defects had fibrous tissue adherent to the implant continuous with the
      overlying soft tissue. Our study demonstrated three points: this membrane can be
      used to increase bone regeneration into defects, this technique allows bone to
      grow directly around an implant, and butyl-cyanoacrylate can be used in deep soft
      tissue and bone applications without any apparent deleterious effects.

PMID- 9619435
TI  - Technique for identification of submicron metal particulate from implants in
      histological specimens.
AB  - Metal implants are being used with increasing frequency for the treatment of many
      diseases in the field of orthopedics, cardiology, cardiovascular surgery, and
      otolaryngology. Unfortunately, metals can be a source of submicron particles,
      which may have adverse effects on tissues. This article describes a technique
      that uses backscattered electron imaging and energy dispersive X-ray
      microanalysis, which have the capacity to perform both quantitative and
      qualitative analysis. The particles can be characterized by size, shape, amount,
      and composition. Although this technique can be used near the implant interface,
      it is particularly helpful in tissues a great distance from the implant site with
      a low concentration of metal debris. In addition, the sensitivity and specificity
      of this technique can be adjusted to the investigator's needs.

PMID- 9619436
TI  - Bruxing-type dental wear simulator for ranking of dental restorative materials.
AB  - An instrumented dental wear test simulator was developed to simulate jaw movement
      in the chewing process between two molar teeth. It simulated the natural impact
      with sliding masticatory action, known as bruxing (defined as the gnashing,
      grinding, or clenching of teeth) type of wear, in order to simulate a worst-case
      dental wear scenario. In vitro wear testing of dental restorative materials was
      performed. Impact and sliding wear were simulated on the machine, with water as
      the lubricant, on three metal alloys (Tytin, Valiant Ph.D., Galloy) and three
      composite resins (Silux Plus, Z100, P50). The impact force for each machine cycle
      was brought closer to the maximum natural masticatory forces by the use of a
      shock absorbing layer. To replicate the natural masticatory action, the specimens
      had a surface profile with the shape of a conical depression. Ranking of the
      materials' performance on the wear test simulator was seen to be consistent with
      published clinical ranking. Metal alloys showed greater wear resistance than
      composite resins. Among the different metal alloys, those with lower hardness and
      compressive strengths exhibited greater wear. Composite resins with large filler
      particles wore worse than those with small filler particles. Results were
      compared with previous work on impact with sliding on a flat surface without a
      cushioning layer. It was concluded that the magnitude of the impact force and the
      angle of approach during impact with sliding wear are important parameters in the
      in vitro wear ranking of dental restorative materials.

PMID- 9619437
TI  - Effects of titanium-dental restorative alloy galvanic couples on cultured cells.
AB  - The potential exists for titanium and amalgams to become galvanically coupled in
      the oral cavity. While low galvanic corrosion rates have been measured in vivo
      for titanium-amalgam or mercury-free alloy couples, concerns exist over released
      corrosion products and adverse tissue responses. It was hypothesized in this
      study that coupling titanium to amalgams or gallium alloys increased the release
      of metallic corrosion products and decreased cellular activity and function. The
      effects of titanium coupled and uncoupled to a conventional amalgam, palladium
      enriched spherical high copper amalgam, a dispersed type high copper amalgam, and
      a mercury-free gallium alloy were evaluated in 24-h cell culture tests.
      Viability, proliferation, and collagen synthesis were evaluated by the uptake of
      neutral red, 3H-thymidine, and immunoassay of procollagen, respectively, and
      compared to cells not exposed to any test material. The gallium alloy-titanium
      couple resulted in significant decreases in cellular viability, proliferation,
      and collagen synthesis as compared to the other coupled and uncoupled samples.
      Few differences in the cellular responses of the other coupled and uncoupled
      samples were observed. Atomic absorption analyses indicated increased release of
      metal ions from the amalgam and gallium alloy samples coupled to titanium as
      compared to their uncoupled condition, although the differences were not always
      significant. Galvanic corrosion of amalgam-titanium couples in the long term may
      become significant, and further research is needed. Coupling the gallium alloy to
      titanium may result in increased galvanic corrosion and cytotoxic responses.

PMID- 9619438
TI  - Timing of loading and effect of micromotion on bone-dental implant interface:
      review of experimental literature.
AB  - A significant no-load healing period is the generally accepted prerequisite for
      osseointegration in dental implantology. The aim of this article was to examine
      whether this no-load healing period is validated by the experimental literature.
      In vivo histological data was scrutinized to identify the effect of early loading
      protocols on the bone-implant interface. Several loading modes were identified.
      They were categorized into groups according to implant design and the type of
      prosthetic reconstruction, and by their ability to introduce a distinct magnitude
      of motion at the interface. Specific histologic responses of early loaded
      implants (i.e., fibrous repair or osseointegration) were suggested to be directly
      related to the specific combinations of the above parameters. Early loading per
      se was not found to be detrimental to osseointegration. Specifically, only
      excessive micromotion was directly implicated in the formation of fibrous
      encapsulation. The literature suggests that there is a critical threshold of
      micromotion above which fibrous encapsulation prevails over osseointegration.
      This critical level, however, was not zero micromotion as generally interpreted.
      Instead, the tolerated micromotion threshold was found to lie somewhere between
      50 and 150 microns. Suggestions are made for the earliest loading time that
      achieves osseointegration.

PMID- 9619439
TI  - Organ culture in 3-dimensional matrix: in vitro model for evaluating biological
      compliance of synthetic meshes for abdominal wall repair.
AB  - A new in vitro method to evaluate the early critical interactions between
      synthetic prosthetic materials and growing tissues is reported. The correct
      spatial organization and proper cell to cell interaction required to mimic the in
      vivo environment was obtained in a 3-dimensional (3-D) embryo organ culture. The
      clot formed by plasma and chick-embryo extract provided a natural 3-D
      extracellular matrix that was able to support the growth and differentiation of
      intestinal tissue dissected from 12-day-old chick embryos. Different materials
      used for the repair of abdominal wall defects were taken as standards; all the
      prosthetic materials were devoid of any evident cytotoxic potential over a 10-day
      culture period, so they did not interfere with the organogenesis process. A
      polyglactin mesh (Vicryl) was fully incorporated into the growing tissue, but
      early signs of its degradation were detectable. The biologically inert materials
      polyethylene terephthalate (Mersilene) and polypropylene (Marlex, Prolene, and
      Herniamesh) retained their structural integrity when incubated with cultured
      tissue at 37 degrees C, and they did not hinder cellular proliferation or
      fibroblast migration. However, the outgrowth behavior was very different while
      the connective tissue invaded the interstices of the polyethylene terephthalate
      mesh; the explants and the migrating cells were repelled by hydrophobic
      polypropylene meshes. These findings are in agreement with other reported results
      in in vivo studies. Therefore, this method can be considered as reliable and
      predictable for the evaluation of biopolymers.

PMID- 9619440
TI  - New ferromagnetic bone cement for local hyperthermia.
AB  - We have developed a ferromagnetic bone cement as a thermoseed to generate heat by
      hysteresis loss under an alternate magnetic field. This material resembles
      bioactive bone cement in composition, with a portion of the bioactive glass
      ceramic component replaced by magnetite (Fe3O4) powder. The temperature of this
      thermoseed rises in proportion to the weight ratio of magnetite powder, the
      volume of the thermoseed, and the intensity of the magnetic field. The heat
      generating ability of this thermoseed implanted into rabbit and human cadaver
      tibiae was investigated by applying a magnetic field with a maximum of 300 Oe and
      100 kHz. In this system, it is very easy to increase the temperature of the
      thermoseed in bone beyond 50 degrees C by adjusting the above-mentioned control
      factors. When the temperature of the thermoseed in rabbit tibiae was maintained
      at 50 to 60 degrees C, the temperature at the interface between the bone and
      muscle (cortical surface) surrounding the material rose to 43 to 45 degrees C;
      but at a 10-mm distance from the thermoseed in the medullary canal, the
      temperature did not exceed 40 degrees C. These results demonstrate that
      ferromagnetic bone cement may be applicable for the hyperthermic treatment of
      bone tumors.

PMID- 9619441
TI  - What role will chairs of discipline-based subjects play in the evolving medical
      school of the future?

PMID- 9619442
TI  - Influence of host genes on HIV-1 disease progression.
AB  - The role of host genes in the course of HIV-1 infection has been examined in
      different populations and among all major risk groups. Two extended human
      lymphocyte antigen (HLA) haplotypes, HLA A1-Cw7-B8-DR3-DQ2 and HLA A11-Cw4-B35
      DR1-DQ1, are found to be associated with a faster progression to AIDS. The
      complement C4 factor and tumor necrosis factor genes of the major
      histocompatibility complex, as well as the mannose binding protein gene, have
      also been suggested to influence the outcome of AIDS. The recent discovery that
      chemokine receptors could serve as cofactors for HIV-1 cell entry has prompted a
      search for polymorphisms in chemokine receptor genes. A 32 base pair inactivating
      deletion in the CCR5 gene and a point mutation within the CCR2b gene resulting in
      a conservative amino acid substitution have been examined and shown to be
      independently associated with delayed disease progression. Together, these
      observations strongly support a genetic component in AIDS pathogenesis. This
      article synthesizes the current state of knowledge about the influence of host
      genes on HIV-1 disease progression. It provides a summary of all significant
      association studies reported so far. The role of the allelic polymorphism in
      these genes is discussed with regard to the immunopathogenesis of AIDS.

PMID- 9619443
TI  - The molecular role of Myc in growth and transformation: recent discoveries lead
      to new insights.
AB  - A major dilemma facing the Myc researcher is understanding how c-Myc regulation
      of gene transcription translates into the proliferative and oncogenic activities
      mediated by c-Myc protein. Indeed, much effort has focused on attempting to link
      c-Myc activation of gene transcription with both cell cycle progression and
      transformation mechanisms. Considerable progress has been made in recent years,
      with the identification of new Myc binding proteins as well as novel cellular
      targets of Myc-Max complexes. These discoveries have yielded more than a few
      surprises and challenged those working in the field to rethink traditional
      paradigms. It is now evident that c-Myc can also repress the transcription of
      specific genes, and Myc-mediated repression appears to be linked to Myc-dependent
      transformation. We summarize the evidence on Myc biological and molecular
      functions with regard to Myc-Max transcriptional regulation. In addition, we
      reevaluate current models of Myc transcriptional modulation in light of the
      discovery of new Myc binding partners and novel downstream target genes. Finally,
      we explore whether direct transactivation of cellular genes by Myc-Max
      heterodimers is sufficient for the growth-promoting and transforming activities
      of Myc or whether other molecular activities of Myc, such as Myc-mediated
      repression, may play a key role.

PMID- 9619444
TI  - Prediction-based threading of the hMSH2 DNA mismatch repair protein.
AB  - Mutations in the genes whose products participate in DNA mismatch repair underlie
      the increased risk of cancer in families with hereditary nonpolyposis colon
      carcinoma. Mutations in hMSH2 account for approximately 50% of the mutations
      found in these families. We sought to predict the 3-dimensional structure of
      hMSH2 by identifying structural homologues using prediction-based threading and
      by computer modeling using information from these putative structurally related
      proteins. Prediction-based threading identified three candidate structural
      homologues: glycogen phosphorylase (gpb), a 70 kDa soluble lytic
      transglycosylase, and ribonucleotide reductase protein R1. An independent
      approach utilizing a potential-based threading program also identified gpb as a
      structural homologue. The models based on the structures of these proteins
      suggest that the ATP binding domain and helix-turn-helix domain are exposed on
      the outside of the protein. All known bacterial MutS and hMSH2 mutations appear
      to be clustered in similar vicinities in the theoretical models of hMSH2; the
      major site is within the ATP binding domain and near the carboxyl-terminal end,
      whereas a smaller number map to the region coding for exon 5 and the amino
      terminal domain. All point mutations also appear to affect amino acids that are
      exposed on the outside surface of the protein.

PMID- 9619445
TI  - Activation of EGF receptor by oxidized LDL.
AB  - Oxidized low density lipoproteins (oxLDL) are thought to play a major role in
      atherosclerosis. OxLDL exhibit a wide variety of biological effects resulting
      from their ability to interfere with intracellular signaling. The cellular
      targets and primary signaling events of oxLDL are unknown. We report that oxLDL
      elicit, in intact cells, tyrosine phosphorylation of the epithelial growth factor
      receptor (EGFR) and activation of its signaling pathway. This activation
      triggered by oxLDL was associated with derivatization of reactive amino groups of
      EGFR and was mimicked by 4-hydroxynonenal (4-HNE, a major lipid peroxidation
      product of oxLDL). Immunopurified EGFR was derivatized and activated in vitro by
      oxLDL lipid extracts and 4-HNE, thus indicating that 1) EGFR may be a primary
      target of oxidized lipids and 2) EGFR derivatization may be associated with
      activation. The reported data suggest that EGFR acts as a sensor for oxidized
      lipids. We therefore propose a novel concept of the mechanism by which oxidized
      lipids (contained in oxLDL or more generally produced during oxidative stress)
      are able to activate receptor tyrosine kinase and subsequent signaling pathways,
      resulting finally in a gain of function.

PMID- 9619446
TI  - Bacterial lipopolysaccharide induces endothelial cells to synthesize a
      degranulating factor for neutrophils.
AB  - Enzymes and other factors secreted by degranulating neutrophils
      (polymorphonuclear leukocytes, PMNs) mediate endothelial injury, thrombosis, and
      vascular remodeling. In bacteremia and sepsis syndrome and their consequent
      complications (including acute respiratory distress syndrome and systemic
      ischemia-reperfusion resulting from septic shock), neutrophil degranulation is an
      important mechanism of injury. In related studies, we found that human
      endothelial cells regulate neutrophil degranulation and that inflammatory
      cytokines induce synthesis of degranulating factors by human endothelial cells.
      Here we show that lipopolysaccharides (LPS) from gram-negative bacteria were the
      most potent agonists for release of degranulating activity by endothelial cells
      when compared to several cytokines and stimulatory factors. LPS also induced the
      release of degranulating signals for PMNs from a human endothelial cell line,
      EA.hy 926. Interleukin 8 (IL-8) is synthesized by endothelial and EA.hy 926 cells
      in response to LPS and induces neutrophil degranulation. However, complementary
      strategies using receptor desensitization, translation of messenger RNA by
      Xenopus laevis oocytes, and purification and analysis of factors from conditioned
      supernatants demonstrated that degranulating factors distinct from IL8 are
      generated in response to LPS. The characteristics of a partially purified
      degranulating factor isolated from conditioned supernatants distinguished it from
      known chemokines and other factors that induce PMN degranulation and are
      generated by endothelial cells in response to LPS. Thus, cultured human
      endothelial cells and endothelial cell lines synthesize several unique signaling
      molecules that can trigger neutrophil granular secretion. If produced in vivo in
      response to LPS or other pathologic agonists, these degranulating signals may
      activate PMNs in combination or in sequence, initiating or propagating vascular
      damage.

PMID- 9619447
TI  - Melatonin inhibits expression of the inducible isoform of nitric oxide synthase
      in murine macrophages: role of inhibition of NFkappaB activation.
AB  - The role of melatonin as an immunomodulator is well established. Recent reports
      showed that melatonin exerts protective effects in septic and hemorrhagic shock
      and in inflammation. The expression of the inducible isoform of nitric oxide
      synthase (iNOS) makes an important contribution to the pathophysiology of shock
      and inflammation. We studied, in cultured murine macrophages, the role of
      melatonin in the regulation of the expression of iNOS and defined the mode of
      melatonin's action. Our results show that melatonin, at 1 microM-1 mM, decreased
      the production of nitrite/nitrate (the breakdown products of NO) as well as the
      production of 6-keto-prostaglandin F1alpha (the major stable breakdown product of
      prostacyclin) in macrophages stimulated with bacterial lipopolysaccharide (10
      microg/ml). We observed that melatonin reduces iNOS steady-state mRNA levels and
      iNOS protein expression in the same concentration range (1 microM-1 mM).
      Melatonin, up to 10 mM, exerted only a slight direct inhibitory effect on iNOS
      activity. Using iNOS promoter-luciferase constructs, we found that melatonin
      inhibits iNOS promoter activation. Inhibition of iNOS expression was associated
      with inhibition of activation of the transcription factor nuclear factor kappa B
      (NFkappaB). We conclude that melatonin inhibits NO production in immunostimulated
      macrophages mainly by inhibiting the expression of iNOS. This is due to
      inhibition of iNOS transcription, in part through inhibition of NFkappaB
      activation. Inhibition of iNOS-derived NO production by melatonin may contribute
      to the anti-inflammatory effects of this pineal secretory product.

PMID- 9619448
TI  - Recombinant soluble low density lipoprotein receptor fragment inhibits minor
      group rhinovirus infection in vitro.
AB  - A fragment of the low density lipoprotein receptor encompassing the seven ligand
      binding repeats was expressed in Sf9 insect cells as a fusion protein with a
      carboxyl-terminally linked hexa-his tag by using a baculovirus vector. Up to 10
      mg/l of the fusion protein was secreted into the medium. The material was soluble
      in the absence of detergent and active in binding beta very low density
      lipoprotein and a member of the minor group of human rhinoviruses (HRV2) in
      ligand blots from sodium dodecyl sulfate-polyacrylamide gels run under
      nonreducing conditions. The receptor fragment specifically inhibits viral
      infection of HeLa cells by minor group HRVs in a concentration-dependent manner.
      Viral infectivity is neutralized by aggregation.

PMID- 9619449
TI  - Human IP-10 selectively promotes dominance of polyclonally activated and
      environmental antigen-driven IFN-gamma over IL-4 responses.
AB  - Human interferon-inducible protein 10 (IP-10) differs from most chemokines in its
      apparent specificity for activated T lymphocytes. We hypothesized that IP-10 was
      relevant not only for recruiting T cells to inflammatory sites, but also for
      regulating cytokine synthesis patterns. We examined the effect of recombinant
      human IP-10 (rhIP-10) on human interferon gamma (IFN-gamma) and interleukin 4 (IL
      4) production by fresh peripheral blood mononuclear cells. We demonstrate for the
      first time that this CXC chemokine selectively up-regulates human T cell cytokine
      synthesis, with enhancement selectively targeted to promotion of Th1-like
      dominance. Superantigen (TSST-1), soluble anti-CD3 mAb, and phytohemagglutinin
      were used to activate distinct intracellular signaling pathways, thereby inducing
      quantitatively different IFN-gamma:IL-4 ratios. Selective enhancement of IFN
      gamma responses was consistently observed, with median increases of 105-470%.
      Environmental antigens (Ag) were used to evaluate IP-10's effect on CD4
      dependent, chloroquine-sensitive cytokine synthesis. Ag-driven IFN-gamma
      responses exhibited median 19- to 30-fold increases in the presence of nanomolar
      concentrations of rhIP-10. IL-4 responses were neither enhanced nor inhibited
      under any of the conditions tested. These findings suggest a potential role for
      this T cell-focused chemokine in maintenance of the default Th1-like responses
      usually seen to environmental Ag and indicate a potential application in the
      modulation of Ag-driven responses in vivo.

PMID- 9619450
TI  - Role of UCP homologues in skeletal muscles and brown adipose tissue: mediators of
      thermogenesis or regulators of lipids as fuel substrate?
AB  - The mRNA expressions of UCP2 and UCP3, two newly described genes with high
      sequence homology to the uncoupling protein UCP1 in brown adipose tissue (BAT),
      were examined in two skeletal muscles (gastrocnemius and soleus) as well as in
      interscapular BAT (IBAT) of the rat in response to food deprivation and
      controlled refeeding. In IBAT (a tissue highly dependent on lipids for
      thermogenesis), the pattern of mRNA expression of UCP2 and UCP3 closely follows
      that of UCP1: it was markedly down-regulated during food deprivation (when this
      tissue's thermogenesis and lipid fuel requirements are decreased) and restored to
      control levels by day 5 of refeeding. By contrast, in the gastrocnemius muscle (a
      mixed fiber type muscle with a high capacity to shift between glucose and lipids
      as fuel substrate), mRNA expression of both UCP2 and UCP3 mRNA was found to be
      markedly up-regulated during food deprivation (when this tissue's thermogenesis
      is also decreased but its lipid fuel utilization is increased). The expressions
      were subsequently found to be markedly down-regulated upon transition to
      refeeding, with mRNA levels remaining below control levels on days 3, 5, and 10
      of refeeding (period of enhanced efficiency of body fat deposition). In the
      soleus muscle (an oxidative type muscle with higher dependency on lipids than the
      gastrocnemius, and hence with a lower capacity to shift between lipids and
      glucose as fuel substrate), UCP homologues were also found to be up-regulated
      during food deprivation, but changes in their mRNA expression contrast with those
      in the gastrocnemius muscle both in their much lower magnitude of response to
      food deprivation and in their more rapid restoration to control levels during
      refeeding. Up-regulation of UCP2 and UCP3 gene expressions in skeletal muscle
      during food deprivation was found to persist at thermoneutrality (i.e., under
      conditions of reduced thermoregulatory thermogenesis). Together, these tissue
      dependent differential mRNA expressions of the UCP homologues in IBAT,
      gastrocnemius, and soleus muscles during food deprivation and refeeding are much
      more consistent with a role for UCP2 and UCP3 in the regulation of lipids as fuel
      substrate rather than as mediators of regulatory thermogenesis.

PMID- 9619451
TI  - Melatonin prevents the delayed death of hippocampal neurons induced by enhanced
      excitatory neurotransmission and the nitridergic pathway.
AB  - The mechanisms by which neurons die after stroke and status epilepticus and
      related neuropathological conditions are unclear, but may involve voltage
      dependent Na+ channels, glutamate receptors, and nitric oxide (NO.). These
      questions were investigated using an in vitro primary cell culture model in which
      hippocampal pyramidal neurons undergo a gradual and delayed neurodegeneration
      induced by enhanced excitatory neurotransmission. When cells were treated with
      Mg2+-free, glycine-supplemented medium for a brief period (15 min) and examined
      24 h later, approximately 30-40% of the neurons had died. Cell death could be
      inhibited by blockers of voltage-sensitive Na+ channels and by N-methyl-D
      aspartate receptor antagonists. Application of either the endogenous antioxidant
      melatonin (EC50: 19.2+/-2.8 microM) or the NO. synthase inhibitor Nomega-nitro-L
      arginine after, but not during, Mg2+-free exposure protected against delayed
      neuronal death; significant neuroprotection was observed when the addition was
      delayed for up to 4 h. This operational time window suggests that an enduring
      production of NO. and reactive oxygen species from neuronal sources is
      responsible for delayed cell death. A role for reactive oxygen species in this
      injury process was strengthened by the finding that, whereas neurons cocultured
      with astroglia were more resistant to killing, agents capable of lowering
      intracellular glutathione negated this protection. Because secretion levels of
      melatonin are decreased with aging, reductions in this pineal hormone may place
      neurons at a heightened risk for damage by excitatory synaptic transmission.

PMID- 9619452
TI  - Human endothelial cells regulate polymorphonuclear leukocyte degranulation.
AB  - Neutrophil degranulation is an important event in inflammatory responses. We
      examined the regulation of neutrophil (PMN) degranulation by resting and
      activated human endothelial cells. Whereas PMNs adherent to endothelial cells
      that were stimulated to express P-selectin and platelet-activating factor did not
      release the specific granule marker lactoferrin or the primary granule enzyme,
      elastase, PMNs adherent to endothelial cells stimulated with interleukin-1 (IL-1)
      or tumor necrosis factor secreted both. PMN degranulation was dependent on the
      time of incubation of endothelial cells with the cytokine, its concentration, and
      the time of incubation of the PMNs with endothelial cells. Degranulation of PMNs
      and their adhesion to stimulated endothelial cells are correlated events, but
      they could be dissociated by blocking the tethering molecules used by the
      endothelial cells and neutrophils under these conditions. This suggested that
      paracrine signaling molecules that induce PMN degranulation are produced by
      cytokine-stimulated endothelial cells. We found that endothelial cells stimulated
      with IL-1 release newly synthesized degranulating factors that require
      transcription and translation. IL-8 was synthesized, released, and signaled
      granular secretion by PMNs. However, experiments with blocking antibodies
      indicated the presence of an additional degranulating factor not accounted for by
      IL-8. These experiments demonstrate that human endothelial cells regulate
      degranulation of neutrophils by generating signaling factors that are expressed
      differentially depending on the endothelial agonist and other features. Active
      modification of neutrophil granular secretion by endothelial cells can influence
      physiologic acute inflammatory responses but may also contribute to pathologic
      vascular and tissue damage.

PMID- 9619453
TI  - High expression of leptin by human bone marrow adipocytes in primary culture.
AB  - Adipocytes participate in the microenvironment of the bone marrow (BM), but their
      exact role remains to be determined. It has recently been shown that leptin, a
      hormone secreted from extramedullary adipocytes, could be involved in
      hematopoiesis. Therefore we have developed a primary culture system of human BM
      adipocytes to characterize their differentiation and determine whether leptin is
      also secreted from these adipocytes. BM cells were cultured with fetal calf and
      horse sera. In the presence of dexamethasone, cells with vesicles containing
      lipids appeared within 15 days. They expressed glycerol phosphate dehydrogenase
      activity and a lipolytic activity in response to isoproterenol, but expressed
      neither the adrenergic beta3 receptor nor the mitochondrial uncoupling protein
      UCP1. The addition of insulin alone to the culture media did not promote
      adipocyte differentiation. Leptin was expressed and secreted at high levels
      during adipocyte differentiation. Acute exposure of differentiated adipocytes to
      insulin had little effect on leptin expression whereas forskolin strongly
      inhibited it. These results show that although human BM adipocytes differ from
      extramedullary adipose tissues in their sensitivity to different effectors, they
      are a secondary source of leptin production. They suggest that BM adipocytes
      could contribute to hematopoiesis via the secretion of leptin in the vicinity of
      hematopoietic stem cells.

PMID- 9619454
TI  - DNA alterations in rat organs after chronic exposure to cigarette smoke and/or
      ethanol ingestion.
AB  - In spite of the epidemiological evidence supporting a synergism between alcohol
      consumption and cigarette smoking in the pathogenesis of cancers of the
      aerodigestive tract, there is a paucity of experimental studies evaluating the
      effects of these agents under well-controlled conditions and exploring the
      mechanisms involved. We exposed groups of female BD6 rats, aged 8 months, to
      ethanol (5% in drinking water for 8 consecutive months) and/or whole-body to
      mainstream cigarette smoke (1 h/day, 5 days/week for 8 months). DNA was purified
      from different organs and analyzed for the presence of DNA-protein crosslinks and
      32P-postlabeled DNA adducts after butanol enrichment. No significant increase of
      DNA-protein crosslinks, compared to untreated controls, was induced by any
      treatment in liver, lung, or heart. 'Spontaneous' nucleotidic modifications were
      detected by 32P-postlabeling in organs of untreated rats, with the highest levels
      occurring in the heart. Ingestion of ethanol did not affect DNA adduct levels in
      any of the organs examined: esophagus, liver, lung, and heart. Exposure to
      cigarette smoke induced formation of DNA adducts in the lung and heart, but not
      in the esophagus or liver. The combined ingestion of ethanol resulted in a
      significant formation of smoke-related DNA adducts in the esophagus and in their
      further, dramatic increase in the heart. It thus appears that ethanol consumption
      increases the bioavailability of DNA binding smoke components in the upper
      digestive tract and favors their systemic distribution. The mechanisms
      responsible for the interaction between ethanol and smoke and for the selective
      localization of DNA alterations in different organs are discussed. Formation of
      DNA adducts in the organs examined may be relevant in the pathogenesis of lung
      and esophageal cancers as well as in the pathogenesis of other types of chronic
      degenerative diseases, such as chronic obstructive pulmonary diseases and
      cardiomyopathies.

PMID- 9619455
TI  - Irreducible fracture-dislocation of the hip: a severe injury with a poor
      prognosis.
AB  - OBJECTIVE: To determine the outcome of and prognostic factors associated with
      irreducible fracture-dislocations of the hip. DESIGN: Retrospective review of a
      prospectively gathered trauma database. METHODS: Using a prospectively gathered
      trauma database, we identified twenty-five patients with fracture-dislocations of
      the hip that were irreducible with closed means under a general anaesthetic. All
      were victims of high-energy trauma with severe injuries (mean Injury Severity
      Score = 25, range 9 to 54). Eighteen patients had multiple fractures, fifteen had
      associated systemic injury, and only four sustained the hip injury in an isolated
      fashion. There were seven associated sciatic nerve injuries (28 percent) and nine
      associated femoral head or neck fractures (36 percent). The mean time from injury
      to open reduction was 15.3 hours (range 3 to 58 hours). RESULTS: Twenty-three
      patients (92 percent) were followed to definitive outcome. Despite accurate
      reduction, only six patients had satisfactory results (Thompson-Epstein = good or
      excellent). Poor results were associated with delay in reduction and an
      associated femoral head or neck fracture. Reasons for the poor results include
      avascular necrosis, posttraumatic arthritis or chondrolysis, persisting sciatic
      nerve injury, and heterotopic ossification. CONCLUSIONS: An irreducible fracture
      dislocation of the hip is a severe injury with a poor prognosis and a high
      incidence of associated injuries. Outcome is best in patients who do not have an
      associated femoral head or neck fracture and those whose dislocation is promptly
      reduced.

PMID- 9619456
TI  - Predictors of early failure of fixation in the treatment of displaced subcapital
      hip fractures.
AB  - OBJECTIVE: To examine predictors of fixation failure in the treatment of
      displaced subcapital hip fractures. DESIGN: Retrospective study. METHODS: All
      patients aged sixty-five years and older discharged from a large teaching
      hospital after treatment for displaced subcapital fracture between April 1, 1989
      and February 29, 1995 were identified (n = 344). Of these, 108 patients treated
      with internal fixation became the study group. Clinical information included
      demographics, implant, comorbidity, complications, mortality, surgeon' s
      assessment of reduction, and need for revision. Preoperative x-ray information:
      Garden grade, Singh Index, Pauwel's angle, medial neck and femoral shaft cortex
      width, and displacement of fracture fragments. Postoperative: Quality of
      reduction, a visible gap or step, evidence of union, fracture collapse, and
      failure. RESULTS: The failure rate was 31 percent. The two most important
      predictors were varus reduction and perceived difficulty in achieving reduction.
      If the patient had a varus reduction or the surgeon had difficulty achieving a
      satisfactory reduction, fixation was 4.3 times more likely to fail (p = 0.007).
      If the patient had a varus reduction and reduction was difficult, fixation was
      13.6 times more likely to fail (p = 0.04). Under this latter scenario, 75 percent
      of the fixations failed. CONCLUSION: In a fracture of the neck of the femur, if
      difficulty is encountered in obtaining a closed reduction or there is residual
      varus angulation, the chance of subsequent fixation failure is high.
      Hemiarthroplasty may be considered in these cases.

PMID- 9619457
TI  - Unstable femoral neck fractures in young adults: treatment with the AO 130-degree
      blade plate.
AB  - OBJECTIVE: To evaluate the clinical outcome of the treatment of unstable femoral
      neck fractures using the AO 130-degree blade plate. DESIGN: Between 1980 and
      1994, thirty-four consecutive patients younger than age fifty years with an
      unstable intracapsular femoral neck fracture (Garden Types III-IV) were treated
      with internal fixation. SETTING: University Hospital Gasthuisberg, Leuven,
      Belgium. INTERVENTION: The AO 130-degree blade plate with an antirotation, 6.5
      millimeter, partially threaded cancellous lag screw was used. RESULTS: Nineteen
      (63.3 percent) patients had an excellent result, seven (23.3 percent) had a good
      result, three (10 percent) had a fair result, and one (3.3 percent) had a poor
      result. Delayed union was observed in one case, and avascular necrosis was
      observed in two cases. Two implants perforated the subchondral bone. CONCLUSION:
      Stable fixation with the AO 130-degree blade plate avoids damage to the adjacent
      blood supply to the femoral head and appears to guarantee a good final outcome of
      unstable intracapsular femoral neck fractures in young adults.

PMID- 9619458
TI  - Dynamic hip screw with trochanteric stabilizing plate in the treatment of
      unstable proximal femoral fractures: a comparative study with the Gamma nail and
      compression hip screw.
AB  - OBJECTIVE: To compare the results after operative treatment of unstable per- and
      subtrochanteric fractures with the Gamma nail, compression hip screw (CHS), or
      dynamic hip screw with a laterally mounted trochanteric stabilizing plate
      (DHS/TSP). DESIGN: Prospective. PATIENTS: One hundred seventy patients with
      unstable trochanteric femoral fractures surviving six months after operation.
      Eighty-five patients were randomized to treatment with the Gamma nail (n = 50,
      Gamma group) or the compression hip screw (n = 35, CHS group) and compared with a
      consecutive series of eighty-five patients operated with the dynamic hip screw
      with a laterally mounted trochanteric stabilizing plate (DHS/TSP group) MAIN
      OUTCOME MEASUREMENTS: Radiographs were analyzed for fracture classification,
      evaluation of fracture reduction, implant positioning, later fracture
      dislocation, and other complications. Pre- and postoperative functional status of
      the patients were recorded, with a minimum of six months follow-up. RESULTS:
      Eighteen percent of the patients in the Gamma group, 34 percent in the CHS group,
      and 9 percent in the DHS/TSP group suffered significant secondary fracture
      dislocation during the six months follow-up, leading to a varus malunion, lag
      screw cutout, or excessive lag screw sliding with medialization of the distal
      fracture fragment. Two patients (4.0 percent) in the Gamma group suffered an
      implant-related femoral fracture below the nail, and one had a deep infection.
      The reoperation rates were 8.0 percent in the Gamma group, 2.9 percent in the CHS
      group, and 5.9 percent in the DHS/TSP group. All but one fracture in the Gamma
      and CHS groups and two fractures in the DHS/TSP group healed within six months.
      Approximately three-fourths of the patients had returned to their preoperative
      walking ability after six months, with a trend toward better functional outcome
      in the DHS/TSP group. Use of a TSP reduced the secondary lag screw sliding as
      compared with the conventional CHS, without affecting fracture healing.
      CONCLUSION: The TSP may be an aid in the treatment of these difficult fractures
      because the problem with femoral shaft fractures using the Gamma nail is avoided
      and the medialization of the distal fracture fragment frequently associated with
      the CHS is prevented.

PMID- 9619459
TI  - Intramedullary fixation of high subtrochanteric femoral fractures: a study
      comparing two implant designs, the Gamma nail and the intramedullary hip screw.
AB  - OBJECTIVE: To compare two implants, the Gamma nail and the intramedullary hip
      screw (IMHS ), in the treatment of high subtrochanteric femoral fractures. STUDY
      DESIGN: Prospective, nonrandomized clinical study. METHODS: Eighty-seven
      consecutive patients with high subtrochanteric fractures of the Russell-Taylor
      Types 1A and 1B were treated with intramedullary fixation. The first fifty
      patients were treated with the Gamma nail and the next thirty-seven with the
      IMHS. The results of these operations were evaluated after a minimum follow-up of
      twelve months, and special emphasis was put on the complication rate. RESULTS:
      The number of noninfectious complications (intraoperative fractures,
      postoperative refractures and fixation failures) was significantly higher (p =
      0.037) in the Gamma group (11 of 50, 22 percent) than in the IMHS group (2 of 37,
      5 percent). The complication most often associated with the Gamma nail,
      postoperative fracture of the femoral shaft (six in our Gamma group), was not
      encountered with the use of the IMHS. The Gamma group also included three cases
      of intraoperative trochanteric extension of the fracture versus none in the IMHS
      group. The IMHS group included two mechanical fixation failures. CONCLUSIONS: The
      lower complication rate associated with the use of the IMHS implant could be
      attributable in part to the learning curve in the use of intramedullary implants.
      However, we consider that the evolution of the implant design contributes to the
      result.

PMID- 9619460
TI  - Femoral and cruciate blood flow after retrograde femoral reaming: a canine study
      using laser Doppler flowmetry.
AB  - OBJECTIVE: To determine the effect of retrograde femoral reaming on the blood
      flow of the distal femur and the cruciate ligaments. DESIGN: Canine experimental
      study. SETTING: Tertiary referral and teaching hospital in Toronto, Canada.
      PARTICIPANTS: Thirteen skeletally mature, cross-bred dogs. MAIN OUTCOME MEASURE:
      Red cell flux (RCF) was measured by using a laser Doppler flowmetry probe at
      three bone sites in the distal femur (trochlear groove, medial condyle, and
      lateral condyle) and at the midportion of both the anterior and posterior
      cruciate ligaments before and after retrograde femoral reaming. RESULTS: There
      was a significant increase in the mean postreaming RCF at all the bone sites of
      the distal femur compared with prereaming values: trochlear groove (p = 0.0247),
      medial condyle (p = 0.0440), and lateral condyle (p = 0.0042). We also found a
      significant decrease in the mean postreaming RCF at both cruciate ligament sites
      compared with prereaming values (anterior cruciate, p = 0.0004; posterior
      cruciate, p = 0.0006). CONCLUSIONS: Retrograde femoral reaming and intramedullary
      nailing has become a popular option for the treatment of distal femoral and some
      femoral shaft fractures, but concerns regarding the effect of reaming through an
      intraarticular entry portal have been raised. Our experimental study found that
      after reaming perfusion of the anterior cruciate ligament decreased by 52 percent
      and perfusion of the posterior cruciate ligament decreased by 49 percent.
      Diminished perfusion after reaming may delay healing or exacerbate existing
      injury to the cruciate ligaments and adversely affect rehabilitation of the knee
      after femoral fracture.

PMID- 9619461
TI  - Internal fixation of supracondylar femoral fractures: comparative biomechanical
      performance of the 95-degree blade plate and two retrograde nails.
AB  - OBJECTIVE: The biomechanical stability of supracondylar femoral fractures fixed
      with a condylar blade plate (plate), a Green Seligson Henry nail (GSHN), or a new
      retrograde unreamed supracondylar femoral nail (new nail) based on the AO
      unreamed femoral nail were compared. DESIGN: A standardized simulated comminuted
      supracondylar femoral fracture (segmental defect) in fresh frozen paired
      cadaveric femora was stabilized with one of the implants. The interfragmentary
      fracture site stiffness in three directions and axial strength of the fixator
      bone construct were compared (pairwise). RESULTS: The plate versus the new nail
      was (a) axially 10 percent as stiff and 50 percent as strong (ultimate strength),
      (b) as stiff in A/P bending, and (c) five times more stiff in torsion. Varus
      angle at failure under axial load was significantly greater for the plate than
      for the new nail. There were no statistical differences in axial stiffness and
      ultimate strength between the new nail and the GSHN, but the new nail was 50
      percent and 30 percent as stiff in A/P bending and torsion, respectively. The
      magnitude of deformation at failure under axial loading was similar. CONCLUSIONS:
      In fixation of extraarticular comminuted supracondylar distal femur fractures,
      results indicate that (a) the new nail provides equal or greater stability than
      does the plate, except when large torsional loads are anticipated, and (b) the
      new nail provides stability equal to the GSHN for axial loading and lesser
      stability against off-axis loads. As is evident in this and other studies,
      intramedullary implants are less torsionally stiff than are plates. The torsional
      stiffness of the new nail is expected to be sufficient because it is comparable
      to many available nails, and low torsional moments are expected for healing
      femoral supracondylar fractures.

PMID- 9619462
TI  - Optimal location of a single distal interlocking screw in intramedullary nailing
      of distal third femoral shaft fractures.
AB  - OBJECTIVE: This biomechanical study was done to determine the effect of the level
      of a single distal screw in a static intramedullary (IM) femoral nail on the
      stability of fixation of a fracture in the distal third of the femur. DESIGN:
      Fifteen composite fiberglass femora were osteotomized transversely in the distal
      third of the femur. A Grosse-Kempf nail was implanted into the femurs, which were
      divided into three groups of five specimens. Single screw distal nail locking was
      varied distal to the osteotomy site for each group at 2.5, 5.0, and 7.5
      centimeters, respectively. INTERVENTION: All instrumented femurs were mounted on
      a servohydraulic testing machine and fitted with transducers to measure axial,
      rotational, and bending displacements. Specimens were cyclically loaded (one
      hertz) in simultaneous torsion (moment: +/- 10 newton-meters) and axial
      compression (amplitude: 2,000 newtons) for 500 cycles with a 250-pound abductor
      force. MAIN OUTCOME MEASUREMENT: Data from linear and rotational transducers were
      sampled at 100 hertz for five cycles before cycling, every 100 cycles of loading,
      and immediately after cycling. Custom computer software was developed to convert
      transducer signals into static and dynamic measurements of axial motion (in
      millimeters), rotation (in degrees), and angulation (in degrees). RESULTS:
      Osteotomy site dynamic rotation increased significantly in specimens locked at
      7.5 centimeters when compared with the 2.5-centimeter group. There was minimal
      difference between the stability of the 5.0-centimeter and 7.5-centimeter groups.
      There was no significant change in position at the fracture site before or after
      cyclic loading with respect to axial shortening, rotation, or bending. Both
      dynamic axial and angular displacements were also unaffected by screw position.
      CONCLUSION: The location of a single distal interlocking screw in static IM nail
      fixation of distal third femur fractures can significantly affect rotational
      stability but not axial or angular fixation.

PMID- 9619463
TI  - Outcomes following repair of quadriceps tendon ruptures.
AB  - OBJECTIVES: The purpose of this study was to examine critically the outcomes of
      patients sustaining a quadriceps tendon rupture and to compare outcomes in
      patients with bilateral simultaneous ruptures versus a unilateral rupture.
      DESIGN: Retrospective review. SETTING: Patients were treated at a Level I trauma
      center. PATIENTS/PARTICIPANTS: Fifty-one quadriceps tendon ruptures in thirty
      nine patients were evaluated. A mean four-year follow-up (range 13 to 204 months)
      was available for forty-eight tendon ruptures. INTERVENTIONS: All patients except
      one were treated with operative repair of the quadriceps tendon rupture(s). MAIN
      OUTCOME MEASUREMENTS: Patients were assessed by physical examination, Lysholm and
      Tegner scores, a functional questionnaire, quadriceps isokinetic testing, and
      radiographs. RESULTS: A statistically greater number of patients in the bilateral
      simultaneous rupture group had a systemic illness associated with tendon rupture
      (p = 0.014). This result did not adversely affect outcome as compared with
      patients with unilateral ruptures. Mean range of motion was 123 degrees in
      injured knees. Eighty-four percent of working patients returned to their previous
      occupations. More than half the patients, however, in general the most active,
      could no longer participate in their preinjury recreational activities. Fifty
      three percent of unilateral rupture patients had persistent quadriceps strength
      deficits (>20 percent) in the injured extremity. Both quadriceps and hamstring
      isokinetic testing correlated significantly with Lysholm and Tegner scores.
      CONCLUSIONS: Most patients with bilateral simultaneous and unilateral tendon
      repairs can expect a good range of motion and return to their previous
      occupation, but many have persistent weakness and difficulty returning to higher
      level sporting activities.

PMID- 9619464
TI  - Effects of binary decision making on the classification of fractures of the
      ankle.
AB  - OBJECTIVE: To evaluate the effect of binary decision making on interobserver
      reliability in the classification of fractures of the ankle. DESIGN: Radiographic
      review study. PATIENTS/PARTICIPANTS: Observers: two PGY-2 orthopaedic residents,
      two PGY-5 residents, and two orthopaedic attending surgeons. INTERVENTION:
      Radiographs of fifty ankle fractures were classified. Each observer classified
      the radiographs by using the original AO/ASIF system and its recent binary
      modification. MAIN OUTCOME MEASUREMENTS: Interobserver reliability was assessed
      by using a kappa coefficient and compared for the two classification methods.
      RESULTS: The mean kappa value for interobserver reliability for type only and for
      type and group classification when using the original AO/ASIF system was 0.77 and
      0.61, respectively. Using binary decision making, the mean kappa values for type
      only and for type and group were 0.78 and 0.62, respectively. There was no
      statistically significant difference in reliability between the original and
      binary classification systems. CONCLUSION: The interobserver reliability of both
      the original AO/ASIF classification system and its binary modification is
      substantial. The results of the present study, however, cast doubt on the
      effectiveness of binary decision making in improving interobserver reliability in
      the classification of fractures. To our knowledge, this study is the first to
      compare the original AO/ASIF classification system with its binary modification.
      Additional study of other fractures may help elucidate the effectiveness of
      binary decision making in improving interobserver reliability in the
      classification of all fractures.

PMID- 9619465
TI  - Functional outcomes of "floating elbow" injuries in adult patients.
AB  - OBJECTIVES: To assess elbow function, complications, and problems of floating
      elbow fractures in adults receiving surgical treatment. DESIGN: Retrospective
      clinical review. SETTING: Level I trauma center in Kanagawa, Japan. PATIENTS:
      Fourteen patients with fifteen floating elbow injuries, excluding one immediate
      amputation, seen at the Kitasato University Hospital from January 1, 1984, to
      April 30, 1995. INTERVENTION: All fractures were managed surgically by various
      methods. In ten cases, the humeral and forearm fractures were treated
      simultaneously with immediate fixation. In three cases, both the humeral and
      forearm fractures were treated with delayed fixation on Day 1, 4, or 7. In the
      remaining two cases, the open forearm fracture was managed with immediate
      fixation and the humerus fracture with delayed fixation on Day 10 or 25. MAIN
      OUTCOME MEASUREMENTS: All subjects underwent standardized elbow evaluations, and
      results were compared with an elbow score based on a 100-point scale. The
      parameters evaluated were pain, motion, elbow and grip strength, and function
      during daily activities. Complications such as infections, nonunions, malunions,
      and refractures were investigated. RESULTS: Mean follow-up was forty-three months
      (range 13 to 112 months). At final follow-up, the mean elbow function score was
      79 points, with 67 percent (ten of fifteen) of the subjects having good or
      excellent results. The functional outcome did not correlate with the Injury
      Severity Score of the individual patients, the existence of open injuries or
      neurovascular injuries, or the timing of surgery. There were one deep infection,
      two nonunions of the humerus, two nonunions of the forearm, one varus deformity
      of the humerus, and one forearm refracture. CONCLUSION: Based on the present
      data, we could not clarify the factors influencing the final functional outcome
      after floating elbow injury. These injuries, however, potentially have many
      complications, such as infection or nonunion, especially when there is associated
      brachial plexus injury. We consider that floating elbow injuries are severe
      injuries and that surgical stabilization is needed; beyond that, there are no
      specific forms of surgical treatment to reliably guarantee excellent results.

PMID- 9619466
TI  - Optimal position for plate fixation of complex fractures of the proximal radius:
      a cadaver study.
AB  - OBJECTIVE: To determine the optimal postion for plate fixation in complex
      fractures of the proximal radius in which head and neck dissociation occurs.
      DESIGN: Technical study. SETTING: Tertiary referral center, teaching hospital,
      U.S. military. SUBJECTS: Five preserved cadavers. MAIN OUTCOME MEASURE:
      Radioulnar impingement and proximity to neurovascular structures were directly
      measured in elbows plated in each of three positions: neutral, full pronation,
      and full supination. RESULTS: Application of the 2.0-millimeter T-plate to the
      lateral aspect of the radial head and neck with the forearm in neutral position
      had no impingement, whereas application in full pronation resulted in loss of the
      last 30 degrees of supination. Plate application in full supination resulted in
      the loss of the last 10 degrees of pronation. In addition, there was no
      impingement when the 2.7-millimeter plate was applied similarily in the neutral
      position. None of these positions resulted in increased risk to neurovascular
      structures. CONCLUSIONS: The optimal position for plate fixation of complex
      proximal radius fractures is with the forearm in neutral position, with the plate
      applied directly lateral. A larger implant, 2.7 millimeters, may be used if this
      technique is followed without further risk of impingement and loss of motion.

PMID- 9619467
TI  - Cardiac arrest as a result of intraabdominal extravasation of fluid during
      arthroscopic removal of a loose body from the hip joint of a patient with an
      acetabular fracture.
AB  - The case of a fifty-year-old man who suffered an isolated, associated, both
      column fracture of the left acetabulum is presented. He underwent an
      uncomplicated open reduction and internal fixation through an ilioinguinal
      approach. A follow-up computed tomographic scan was performed postoperatively,
      which documented intraarticular fragments. Hip arthroscopy was performed to
      remove the fragments. During the procedure, arthroscopic fluid extravasated
      through the fracture site under pump pressure and resulted in an intraabdominal
      compartment syndrome that presented as cardiopulmonary arrest. An emergent
      exploratory laparotomy was performed to release the fluid and resume blood flow.
      Despite prolonged asystole, the patient survived without neurologic sequelae. The
      literature on compartment syndrome secondary to arthroscopic procedures is
      reviewed. Because of this previously unreported potentially lethal complication,
      we do not advocate hip arthroscopic procedures for acute or healing acetabular
      fractures.

PMID- 9619468
TI  - End caps for the intramedullary nail: a help or a hindrance?
AB  - End caps on intramedullary nails are intended to facilitate removal and to allow
      length adjustment of the nail in situ. A case is reported in which the end cap
      made nail removal technically more difficult.

PMID- 9619469
TI  - It's long-term stressors that take a toll: comment on Cohen et al. (1998)
AB  - In an extremely well-controlled study, Cohen et al. (1998) add to prior knowledge
      of stress-illness relationships by showing that self-reports of stress occurrence
      and duration of 1 month or more, rather than estimates of stressor severity,
      predict susceptibility to experimentally induced colds (i.e., viral replication
      and cold symptoms). Although ruling out obvious behavioral and personality
      factors as causes of the association of stressors to colds, they were unable to
      identify mediational immune factors, a deficit attributable to the difficulty of
      assessing the multi-layered, dynamic physiological processes within the
      bidirectional connections of the nervous (stress) and immune systems. The
      findings provide an interesting complement to data, showing that people use
      stressor duration in evaluating the illness implications of somatic symptoms
      (Cameron et al., 1995), and suggest caution with regard to overestimating the
      prevalence of stress-induced colds in natural settings.

PMID- 9619470
TI  - Types of stressors that increase susceptibility to the common cold in healthy
      adults.
AB  - Two-hundred seventy-six volunteers completed a life stressor interview and
      psychological questionnaires and provided blood and urine samples. They were then
      inoculated with common cold viruses and monitored for the onset of disease.
      Although severe acute stressful life events (less than 1 month long) were not
      associated with developing colds, severe chronic stressors (1 month or longer)
      were associated with a substantial increase in risk of disease. This relation was
      attributable primarily to under- or unemployment and to enduring interpersonal
      difficulties with family or friends. The association between chronic stressors
      and susceptibility to colds could not be fully explained by differences among
      stressed and nonstressed persons in social network characteristics, personality,
      health practices, or prechallenge endocrine or immune measures.

PMID- 9619471
TI  - Preventive counseling of HIV-positive men and self-disclosure of serostatus to
      sex partners: new opportunities for prevention.
AB  - This study examined whether preventive counseling of HIV-positive men (N = 255)
      was associated with self-disclosure of serostatus to sex partners. Men who
      reported being counseled at posttest and at their current HIV clinic to disclose
      their serostatus to partners were more likely to have done so than men counseled
      only at posttest, only at the HIV clinic, or not counseled at either site.
      Disclosure increased with the number of times counseled at the HIV clinic. These
      patterns held for HIV-negative partners, but not for HIV-positive or HIV-unknown
      partners. Disclosure to HIV-negative partners was associated with safer sexual
      practices. The findings suggest that counseling interventions for HIV-positive
      men, when delivered by multiple sources, may provide an effective means of
      increasing disclosure to sexual partners.

PMID- 9619472
TI  - Psychological and cognitive outcomes of a randomized trial of exercise among
      patients with chronic obstructive pulmonary disease.
AB  - Exercise rehabilitation is recommended increasingly for patients with chronic
      obstructive pulmonary disease (COPD). This study examined the effect of exercise
      and education on 79 older adults (M age = 66.6 +/- 6.5 years; 53% female) with
      COPD, randomly assigned to 10 weeks of (a) exercise, education, and stress
      management (EXESM; n = 29); (b) education and stress management (ESM; n = 25); or
      (c) waiting list (WL; n = 25). EXESM included 37 sessions of exercise, 16
      educational lectures, and 10 weekly stress management classes. ESM included only
      the 16 lectures and 10 stress management classes. Before and after the
      intervention, assessments were conducted of physiological functioning (pulmonary
      function, exercise endurance), psychological well-being (depression, anxiety,
      quality of life), and cognitive functioning (attention, motor speed, mental
      efficiency, verbal processing). Repeated measures multivariate analysis of
      variance indicated that EXESM participants experienced changes not observed among
      ESM and WL participants, including improved endurance, reduced anxiety, and
      improved cognitive performance (verbal fluency).

PMID- 9619473
TI  - Memory effects on symptom reporting in a respiratory learning paradigm.
AB  - With odors as conditioned stimuli (CSs) and CO2-enriched air as the unconditioned
      stimulus, participants learned to exhibit respiratory responses and somatic
      complaints on presentation of only the odor CS+. Studied was whether complaints
      during CS+-only trials were inferred from the conditioned somatic responses or
      were based on activated memory of the complaints during acquisition. Participants
      (N = 56) were either attentionally directed away or not from the complaints
      during acquisition, and the effects on somatic complaints during test were
      studied. Respiratory responses, heart rate, and somatic complaints were measured.
      No physiological conditioning effects were found. However, more complaints were
      reported to the CS+ than to the CS- odor, but only when the CS+ was foul
      smelling. This effect was modulated by the attention manipulation, showing that
      the learned complaints during the test phase were based on memory of the
      acquisition complaints and not on physiological responses during the test.

PMID- 9619474
TI  - Risk for hypertension and pain sensitivity in adolescent boys.
AB  - Reduced pain perception has been observed in many studies of spontaneously
      hypertensive rats and human hypertensive patients. To determine whether a reduced
      sensitivity to pain could be observed in a group of clearly normotensive
      individuals who may be at risk for hypertension, a mild to moderate pain stimulus
      was administered to 177 14-year-old boys. Boys with a normatively elevated
      resting systolic blood pressure tolerated mechanical finger pressure
      significantly longer than boys with lower blood pressure. As well, boys with both
      normatively elevated resting systolic blood pressure and a parental history of
      hypertension reported significantly less pain during finger pressure than lower
      risk participants. These findings could not be explained by personality factors
      and suggest that hypertension-related hypoalgesia is associated with processes
      involved in the development of the disorder.

PMID- 9619475
TI  - Self-esteem as a mediator between spousal support and depressive symptoms: a
      comparison of healthy individuals and individuals coping with arthritis.
AB  - This study examined whether self-esteem mediated the effects of both self
      reported positive and negative marital interactions on depressive symptoms and
      whether the relationships among marital interactions, self-esteem, and depressive
      symptoms were stronger for individuals (n = 90) coping with arthritis compared
      with individuals (n = 90) not coping with a chronic illness. Data were drawn from
      the 1986 Americans' Changing Lives national survey. The results of multigroup
      structural equation analysis suggest that mediation depends on the type of
      marital interaction being considered and the group being examined. For the
      arthritis group, self-esteem mediated the relationship between negative marital
      interactions and depressive symptoms, whereas for the healthy group self-esteem
      played no role in mediating the relationship between marital interactions and
      depressive symptoms. Findings underscore the importance of testing moderated
      mediation models of social support.

PMID- 9619476
TI  - Examining the impact of illness representations on psychological adjustment to
      chronic illnesses.
AB  - Illness representations were assessed in 63 adults with rheumatoid arthritis (RA)
      and 66 with multiple sclerosis (MS). The relationship of illness representations
      to concurrent and later mood was explored. MS patients' beliefs in symptom
      variability were associated with higher depressed mood 4 months later, over and
      above initial levels of depression. RA patients who saw RA as curable or who saw
      themselves as responsible for the illness reported significant increases in
      depression over time. Belief in the serious consequences of RA interacted with
      later illness severity to predict change in depression. When belief in the
      serious consequences of RA was high, less severe illness status was associated
      with less depression and more severe illness status was associated with more
      depression. When RA was initially viewed as only moderately serious, less severe
      illness was associated with somewhat higher levels of depression.

PMID- 9619477
TI  - Autonomous regulation and long-term medication adherence in adult outpatients.
AB  - Self-determination theory was applied to explore the motivational basis of
      adherence to long-term medication prescriptions. Adult outpatients with various
      diagnoses who had been on a medication for at least 1 month and expected to
      continue (a) completed questionnaires that assessed their autonomous regulation,
      other motivation variables, and perceptions of their physicians' support of their
      autonomy by hearing their concerns and offering choice; (b) provided subjective
      ratings of their adherence and a 2-day retrospective pill count during an
      interview with a clinical psychologist; and (c) provided a 14-day prospective
      pill count during a subsequent, brief telephone survey. LISREL analyses supported
      the self-determination model for adherence by confirming that patients'
      autonomous motivation for adherence did mediate the relation between patients'
      perceptions of their physicians' autonomy support and their own medication
      adherence.

PMID- 9619478
TI  - Stochastic model of self-regulation decision making exemplified by decisions
      concerning hypoglycemia.
AB  - The following sequence-internal condition --> symptom perception --> appraisal -
      > decision-models various symptom-based self-regulation processes. A formal
      mathematical model describes the first three steps by continuous variables and
      the decisions at the fourth step by binary variables. The stochastic transitions
      between the sequential steps are quantified by transition probabilities. The
      model is illustrated by blood glucose level estimation and detection and
      treatment of hypoglycemia in 78 patients with insulin-dependent diabetes
      mellitus. These patients made 50 to 70 data collection trials over 3 to 4 weeks
      recording perceived symptoms, cognitive-motor performance, subjective estimates
      of blood glucose, decisions about treatment of hypoglycemia, and driving. A
      statistical estimation of the model's parameters demonstrates the utility of this
      approach for understanding the awareness, detection, and treatment of
      hypoglycemia as a process of symptom-based decision making.

PMID- 9619479
TI  - Crowding stress and violent injuries among behaviorally inhibited rhesus
      macaques.
AB  - Environmental stressors and stable individual differences in human behavior have
      both been implicated etiologically in injuries. Because stress-related injuries
      are difficult to study experimentally in humans, the authors examined injury
      incidence in a troop of 21 male and 15 female free-ranging rhesus macaques
      (Macaca mulatta) before, during, and after a 6-month group confinement.
      Individual differences in behavioral inhibition to novelty were assessed, using
      multiple, quantified observations of behavior by 3 independent raters during 3
      previous years. Incidence and severity of medically attended injuries were
      ascertained from veterinary records over a 2-year study period. A 5-fold increase
      in the incidence of injuries was documented during confinement stress, and an
      interaction was found between the stressor and behavioral inhibition in the
      prediction of injury incidence. Highly inhibited animals had significantly higher
      injury rates during confinement, compared with their uninhibited peers, but equal
      or lower rates in the low stress periods that preceded and followed confinement.
      Inhibited individuals appeared to have been specifically targeted for violence
      during the group stressor but were protected under normative, more predictable
      conditions.

PMID- 9619480
TI  - Stage theories of health behavior: conceptual and methodological issues.
AB  - Despite growing interest in stage theories of health behavior, there is
      considerable confusion in the literature concerning the essential characteristics
      of stage theories and the manner in which such theories should be tested. In this
      article, the 4 key characteristics of a stage theory-a category system, an
      ordering of categories, similar barriers to change within categories, and
      different barriers to change between categories--are discussed in detail.
      Examples of stage models of health behavior also are described. Four major types
      of research designs that might be used for testing stage theories are examined,
      including examples from the empirical literature. The most commonly used design,
      which involves cross-sectional comparisons of people believed to be in different
      stages, is shown to have only limited value for testing whether behavior change
      follows a stage process.

PMID- 9619481
TI  - Regulation of immune responses at mucosal surfaces: allergic respiratory disease
      as a paradigm.
AB  - The epithelial surfaces of the respiratory tract represent a fragile interface
      between the immune system and the outside environment. In order to maintain local
      homeostasis, the adaptive immune system must continuously discriminate between
      innocuous antigens which are ubiquitous in the atmosphere, and antigens
      associated with microbial pathogens. Any breakdown in this discrimination process
      can potentially lead to chronic inflammatory disease. The mechanisms employed by
      the mucosal immune system to maintain this delicate balance are many and varied,
      and a comprehensive understanding of how they collectively operate would provide
      novel insight into a wide variety of diseases. This discussion reviews recent
      progress in this area, focusing on allergic respiratory disease as a model for
      the study of immune regulation at mucosal surfaces.

PMID- 9619482
TI  - Dual role of Ras and Rho proteins: at the cutting edge of life and death.
AB  - Small GTP-binding proteins of the Ras superfamily are master controllers of the
      cell physiology. The range of processes in which these proteins are involved
      include cell cycle progression, cell division, regulation of cell morphology and
      motility and intracellular trafficking of molecules and organelles. The study of
      apoptosis, the physiological form of cell suicide, is progressively linking the
      functions of small G proteins to the control of the mechanisms that trigger the
      genetic programmes of cell death. To date, isoforms of the Ras and Rho groups
      have been related to both promotion and suppression of apoptosis. Further,
      signalling pathways driven by these proteins have been associated with the
      function and/or expression of molecules that regulate apoptotic responses. Thus,
      all available evidence points to a critical role for Ras and Rho proteins as
      major gatekeepers of the decision between cellular life and death.

PMID- 9619483
TI  - Correlating sequence variation with HLA-A allelic families: implications for T
      cell receptor binding specificities.
AB  - Six families of HLA-A alleles have been previously proposed on the basis of
      nucleotide sequence and phylogenetic analysis. Here, sequence polymorphism has
      been examined at both the protein and DNA levels in a family specific manner and
      new minimal signatures for each of the families have been delineated. The DNA and
      protein sites that constitute these signatures are distributed throughout the
      length of the sequence and generally do not appear to act to promote structural
      or functional features of the molecules. This is explained by the fact that
      traditional signatures suffer biases where, for example, recombination products
      of low frequency can obscure one family's trend by introducing 'impurities'
      intrinsic to another family. In the absence of complete frequency data, a closer
      approximation of family signatures can be defined by sites that show strong
      correlation with the family groups. Using this description, the amino acid
      positions 62, 97 and 114, localized in the antigen-binding cleft are, in
      combination, sufficient to discriminate between the six families. Thus, while the
      composition of the whole cleft defines the details of antigen specificity, these
      sites in particular, play a key role in modulating supertype peptide specificity
      and T cell recognition.

PMID- 9619484
TI  - Natural killer cell proliferation induced by anti-NK1.1 and IL-2.
AB  - NKR-P1 molecules are involved in natural killing of certain tumour targets.
      Indeed, the NK1.1 (NKR-P1C) molecule is the most specific serological marker on
      murine NK cells in C57BL/6 mice. Previous studies of NKR-P1 have indicated that
      anti-NKR-P1 mAb induced NK cells to kill otherwise insensitive targets, NK cell
      phosphoinositol turnover and Ca++ flux but it was not previously known if all NK
      cells were activated. In this study we report that immobilized anti-NK1.1 also
      specifically induced proliferation as measured by thymidine incorporation. The
      response required low doses of IL-2 for a synergistic effect. Cells stimulated
      with anti-NK1.1 + IL-2 displayed characteristic cytolytic activity against a NK
      sensitive tumour target, YAC-1. However, anti-NK1.1-stimulated cells displayed
      delayed proliferation kinetics, heterogeneity of the expression of the very early
      antigen marker, CD69, and altered expression of the Ly-49 family members when
      compared to NK cells activated by high concentrations of IL-2. Taken together,
      these data demonstrate that immobilized anti-NK1.1 triggers only a subpopulation
      of NK cells.

PMID- 9619485
TI  - The eosinophil leucocyte, a phenotypic marker of resistance to nematode
      parasites, is associated with calm behaviour in sheep.
AB  - The hypothesis that behaviour in sheep is influenced by resistance to infections
      with Trichostrongylus colubriformis and Haemonchus contortus was explored. Sheep
      were assessed phenotypically as resistant and susceptible in four ways and
      thereafter, the effect of resistance on several behavioural traits was measured
      in an arena test. The behavioural parameters recorded for each sheep were:
      approach/avoidance distance; travel; number of moves; and spread. Four phenotypic
      groups of sheep were set up each with two subgroups: ovine lymphocyte antigen
      (OLA) type (subgroups SY1a type vs other types); blood eosinophil leucocyte
      counts (high vs low); T. colubriformis and H. contortus serum antibodies (high vs
      low titres) and faecal egg count (FEC) (high vs low). Only the behavioural
      comparison between sheep with high versus low eosinophil leucocyte count showed
      consistent differences that were statistically significant, although other
      comparisons favoured associations between OLA type SY1a, low FEC and reduced
      approach/avoidance distance and/or locomotor behaviour. The eosinophil leucocyte
      association was established on two non-overlapping test populations of sheep,
      with mean eosinophil leucocyte counts of 3.19 x 10(5)/mL blood for high and 0.83
      x 10(5)/mL blood for low subgroups; results were reproduced on five separate
      occasions over 6 weeks to detect differences as approach/avoidance distance (P <
      0.01), travel (P < 0.01), number of moves (P < 0.01), and spread (P < 0.05). High
      eosinophilia correlated with low FEC for the infected sheep, which identified
      sheep that were resistant to parasites. We concluded, therefore, that the
      resistant sheep were more at ease with the environment of the test than were the
      sheep with low eosinophil leucocyte counts. The strong association between high
      eosinophil leucocyte counts and behaviour is consistent with other reports which
      suggest that retention of normal levels of circulating eosinophil leucocytes is
      associated with resistance to stress.

PMID- 9619486
TI  - Sex-determined resistance against Leishmania mexicana is associated with the
      preferential induction of a Th1-like response and IFN-gamma production by female
      but not male DBA/2 mice.
AB  - Female DBA/2 mice are relatively resistant to infection with Leishmania mexicana
      compared with male mice. Following subcutaneous infection with 5 x 10(6) L.
      mexicana, amastigotes lesion growth in male and female DBA/2 mice was measured
      and the developing immune responses were monitored both in vitro and in vivo.
      Over the 10 week duration of the experiment all male DBA/2 mice developed rapidly
      growing non-healing lesions while female mice either developed no lesions
      whatsoever or developed smaller slower growing lesions than males. Both male and
      female mice produced parasite specific IgG2a during the course of the disease.
      However, significant titres of parasite specific IgG1 antibodies could be
      detected only in male mice indicating a Th2-influenced response in this sex.
      Furthermore, female mice, unlike male mice, developed significant parasite
      induced cutaneous delayed-type hypersensitivity footpad responses, indicating a
      Th1-influenced response in female mice. Although both male and female DBA/2 mice
      infected with L. mexicana displayed a significant increase in the number of cells
      in their draining lymph nodes at week 10 post-infection, no significant
      differences could be observed in the numbers of CD4+, CD8 + T cells as well as B
      cells between male and female DBA/2 mice. However. following in vitro
      stimulation, the lymph node cells from female mice displayed significantly higher
      antigen specific proliferative responses than the males and produced significant
      amounts of IFN-gamma which could not be detected in the equivalent culture
      supernatants from male mice. There were no significant differences in the levels
      of Th2-associated cytokines IL-4 and IL-5, produced by the lymph node cells of
      both sexes. Treatment of female DBA/2 mice with IFN-gamma neutralizing antibody
      following L. mexicana infection resulted in lesion growth equivalent to male
      mice. Conversely, intralesional injections of murine recombinant IFN-gamma
      significantly inhibited lesion growth in male mice.

PMID- 9619487
TI  - The use of recombinant ovine IL-1beta and TNF-alpha as natural adjuvants and
      their physiological effects in vivo.
AB  - In the present study we have investigated the use of recombinant ovine IL-1beta
      and TNF-alpha both alone and in combination, as natural adjuvants in vaccination
      trials in sheep. Initial experiments were conducted to investigate the
      physiological effects of the cytokines in vivo and determine what dose could be
      administered without adverse pyrogenic effects. Even at the maximum dose tested
      (100 microg) the only significant physiological effect was a transient increase
      in body temperature of approximately 2 degrees C in sheep injected with TNF
      alpha. Administration of either cytokine had profound effects on the levels of
      circulating leucocytes for up to 5 days postinjection. The incorporation of
      either IL-1beta or TNF-alpha in aqueous or Al(OH)3 vaccine formulations enhanced
      antibody responses to a recombinant antigen from the cestode parasite Taenia
      ovis. The addition of IL-1beta to aqueous vaccine formulations increased antibody
      responses 15-20-fold and in Al(OH)3 formulations by three to six fold. TNF-alpha
      stimulated 1.5 to six-fold and 2.5 to seven-fold increases in antibody levels in
      aqueous and Al(OH)3-based formulations, respectively, in a dose-dependent manner.
      The addition of either cytokine to Quil A or IFA vaccines did not enhance the
      antibody levels elicited. When 10 microg of both IL-1beta and TNF-alpha were
      incorporated in the aqueous or Al(OH)3 vaccine formulations, increases of 21-fold
      and 25-fold, respectively, were observed in antibody levels. The adjuvant
      activity of IL-1beta and TNF-alpha in combination in the Al(OH)3-based vaccine
      resulted in antibody levels commensurate with those obtained using Quil A or IFA.

PMID- 9619488
TI  - Th1 unresponsiveness can be infectious for unrelated antigens.
AB  - CD4+ T cells may be assigned a functional status (Th1 or Th2) according to the
      cytokines they produce including IL-2, IFN-gamma and IL-4. Th1 and Th2 CD4+ T
      cells deliver different isotype-switching signals to antigen-specific B cells
      which bias the serum Ig isotypes. The stimulation of Th1 or Th2 responses is
      influenced by adjuvants and administration of antigen in IFA results in Th1
      unresponsiveness as evidenced by: (i) reduced T cell proliferation to antigen;
      (ii) reduced IFN-gamma production in response to antigen; and (iii) reduced IgG2a
      isotype antigen-specific antibodies following antigen/CFA challenge. The impact
      of established human gamma globulin (HGG) specific Th1 unresponsiveness on
      subsequent immunization with an unrelated antigen, human serum albumin (HSA) in
      Th1-inducing CFA was then examined. When subsequently challenged with a mixture
      of HSA and HGG in CFA the HGG-specific Th1 unresponsiveness was infectious and
      dominant, preventing the induction of a Th1 response to HSA. Reduced T cell
      proliferation, IFN-gamma production and IgG2a antibody were consequently observed
      in response to HSA. The HGG-specific Th1 unresponsiveness was not infectious when
      HGG/CFA and HSA/CFA were administered at separate sites. This demonstrates that
      antigen-specific Th1 unresponsiveness can be infectious for new, molecularly
      unrelated antigens and supports studies showing that Th1-mediated autoimmune
      diseases such as experimental allergic encephalomyelitis (EAE) and diabetes can
      be ameliorated using antigens molecularly distinct from the disease-inducing
      immunogen.

PMID- 9619489
TI  - Recombination signature of germline immunoglobulin variable genes.
AB  - In human and mouse, the germline contains a tandem array of highly homologous
      variable (V) gene elements which encode part of the antigen-binding region of the
      antibody protein. During evolution this array apparently arose by gene
      duplication followed by diversification of duplicated genes via point mutation
      and recombination. Analysis of germline V gene sequences using a novel algorithm
      shows that major recombination sites coincide with the borders of the leader
      intron and the cap site, consistent with the hypothesis that over evolutionary
      time cDNA derived by reverse transcription of pre-mRNA in B lymphocytes has
      recombined with germline DNA.

PMID- 9619490
TI  - Heterogeneity in heat shock protein genes in Leishmania isolates.
AB  - Leishmaniasis, a group of visceral and cutaneous diseases, is caused by parasites
      belonging to one genus comprising approximately 13 different species. Many
      methods including serological, biochemical and molecular biological techniques
      have been used by various workers to characterize these different species and
      isolates of Leishmania, yet there is no single generally accepted criterion. We
      have identified certain cDNA clones from a library generated from the
      promastigotes of S1 strain of Leishmania donovani and used them as probes for
      identification of various isolates of L. donovani and Leishmania tropica. Two of
      the probes used, E2b (2.0 kb) and E1a (1.3 kb), sequence characterized to be
      hsp70 of Leishmania, were able to distinguish various isolates of L. donovani
      from different geographical origins as well as strains of L. donovani from those
      of L. tropica. Thus, by using recombinant hsp70 cDNA probes, the data indicated
      that there is a considerable degree of heterogeneity in the heat-shock genes of
      Leishmania.

PMID- 9619491
TI  - A convenient and reliable IL-2 bioassay using frozen CTLL-2 to improve the
      detection of helper T lymphocyte precursors.
AB  - The helper T lymphocyte precursor (HTLp) frequency detected in HLA matched
      sibling donors is directed against alloantigens and this frequency has been shown
      to correlate with the development of graft-versus-host disease in the patient
      after bone marrow transplantation. Using limiting dilution analysis the HTLp
      frequency is determined by measuring IL-2 using the IL-2-dependent murine cell
      line CTLL-2. An important factor associated with the successful performance of
      any bioassay is the reliability of the indicator cell line used. When maintained
      in continuous culture, however, the overall sensitivity of this cell line is
      highly variable. To overcome this problem, large batches of CTLL-2 were grown,
      frozen and tested for their ability to detect low levels of IL-2 (0.01 IU) in
      dose response assays. Batches meeting this criterion were stored in liquid
      nitrogen until required. In this study, we investigated the effect of freezing
      and storing large batches of this cell line, thereby assuring a plentiful supply
      of sensitive indicator cells.

PMID- 9619492
TI  - The high cost of stroke to society, the family, and the patient.
AB  - Stroke is the third leading cause of mortality in the United States, after heart
      disease and cancer, and is a major cause of adult disability. Stroke-related
      neurologic deficits affect language, cognition, and motor function. They are
      often persistent, exerting a negative effect on the patient's quality of life.
      Besides affecting the patient, stroke also places a heavy emotional burden on the
      caregivers of patients with stroke. In the United States, the medical and
      nonmedical costs of caring for patients with stroke during the first year after
      their stroke are $30 billion/year, or approximately $50,000/patient. Many strokes
      are preventable, however, through judicious medical or surgical therapies. In
      addition, emerging thrombolytic and neuroprotective drugs, administered early
      after stroke onset, may minimize or eliminate some of the residual deficits
      associated with stroke. A massive educational effort is needed to raise public
      and professional awareness about stroke and emerging stroke therapies.

PMID- 9619493
TI  - The stroke pharmacopeia: current medical therapies.
AB  - Drug therapies that inhibit or reverse thrombus formation are important
      components of the management of acute ischemic stroke. The role of antiplatelet
      and anticoagulant therapies in stroke prevention has been defined, but further
      research is needed to confirm the possible benefits of aspirin, heparin, and low
      molecular-weight heparin products in acute ischemic stroke. Recently, double
      blind, placebo-controlled studies have evaluated the role of the thrombolytic
      agents streptokinase and tissue plasminogen activator (t-PA) in patients with
      acute ischemic stroke. Intravenous t-PA, administered within 3 hours of symptom
      onset at a dose of 0.9 mg/kg, is safe and effective in carefully selected
      patients.

PMID- 9619494
TI  - The stroke pharmacopeia: promising experimental therapies.
AB  - The development of promising acute stroke treatments is the fruit of the growing
      appreciation for the complex biochemical processes within neuronal tissue that
      commence immediately after the onset of ischemia. These biochemical cascades can
      be modified either by direct pharmacologic mitigation or by rapid restoration of
      perfusion and oxygenation. With both interventions, the ischemic tissue can
      remain viable and regain neurologic function rather than progress to infarction.
      Today the two major pharmacologic approaches to stroke therapy are
      neuroprotectants and thrombolytics. Neuroprotectants enable neuronal tissues to
      tolerate periods of minimal perfusion better, whereas thrombolytics facilitate
      reperfusion by disrupting the fresh thrombus. Important classes of
      neuroprotectants include calcium channel antagonists, N-methyl-D-aspartate (NMDA)
      receptor antagonists, benzothiazoles, and free radical scavengers. Pro-urokinase
      is a potentially important investigational thrombolytic. Ancrod, a
      defibrinogenating agent, is also currently being evaluated in acute stroke.

PMID- 9619495
TI  - The stroke therapy research boom: implications for the hospital formulary.
AB  - Research into drug therapy for the acute treatment of ischemic stroke is now
      booming, and a number of promising drugs with very different mechanisms of action
      are at an advanced stage of development. Ideally, use of single agents or
      combinations of agents will result in favorable neurologic and functional
      outcomes for the majority of stroke patients. Given the current focus within our
      society on controlling health care costs, pharmacoeconomic tools will be
      important in determining which of these agents should achieve formulary
      acceptance. Cost-minimization analysis, cost-benefit analysis, cost-effectiveness
      analysis, and cost-utility analysis are all likely to be valuable methodologies
      to aid in decision making. More complex situations may require the use of
      decision-tree analysis.

PMID- 9619496
TI  - Pharmacotherapy and economics of stroke.

PMID- 9619497
TI  - Retinal projections in mice with inherited retinal degeneration: implications for
      circadian photoentrainment.
AB  - The availability of naturally occurring and transgenic retinal mutants has made
      the mouse an attractive experimental model to address questions regarding
      photoentrainment of circadian rhythms. However, very little is known about the
      retinal cells and the retinal projections to the nuclei of the murine circadian
      timing system. Furthermore, the effect of inherited retinal degeneration on these
      projections is not understood. In this report, we have used pseudorabies virus as
      a neuroanatomical tract tracer in mice to address a series of questions: Which
      retinal cells mediate circadian responses to light? What is the nature of the
      retinohypothalamic projection? What is the impact of the inherited retinal
      disorder, retinal degenerate (rd/rd), on the structures of the photoentrainment
      pathway? Our results show that a class ofretinal ganglion cell, morphologically
      similar to the type III ganglion cells of the rat, appears to project to central
      circadian structures of the mouse. They are few in number and sparsely
      distributed throughout the retina. The low number and broad distribution of these
      specialized retinal ganglion cells may be an adaptive mechanism to integrate
      environmental irradiance without compromising the spatial resolution required for
      vision. In addition, viral infection of conelike and rodlike photoreceptors and
      amacrinelike cells suggest that these cells may mediate or contribute to
      circadian responses to light. Inherited retinal degeneration has no obvious
      effect on the anatomy of the retinal cells or their projections to the circadian
      axis. These anatomical findings are consistent with our previous findings showing
      that aged rd/rd mice are capable of regulating their circadian rhythms by light
      with unattenuated sensitivity.

PMID- 9619498
TI  - Transmitter identification in neurons involved in male copulation behavior in
      Lymnaea stagnalis.
AB  - In this paper, we have mapped the cellular localization of various transmitters
      onto the central neurons which are involved in male copulation behavior in
      Lymnaea stagnalis, by combining retrograde tracing with immunocytochemistry and
      in situ hybridization. Evidence is provided that neurons which were backfilled
      from the penis nerve, the sole nerve to innervate the male copulatory organ,
      synthesize a multitude of neuropeptides (APGWamide, Lymnaea neuropeptide tyrosin
      [LNPY], conopressin, pedal peptide, SEEPLY, DEILSR, myomodulin, and Lymnaea
      inhibitory peptide [LIP]) as well as the classical neurotransmitter, serotonin.
      In the anterior lobe, the backfilled neurons mainly contain the tetrapeptide
      APGWamide and conopressin, and not LNPY or pedal peptide. The results suggest a
      central role in the regulation of copulation activity for the anterior lobe
      neurons that produce APGWamide and conopressin. Immunostainings of backfilled
      nervous systems revealed immunopositive axons originating from these neurons to
      form varicosities on the cell somata of neurons in the other clusters
      contributing to the innervation of the male sexual system. Neurons from the right
      parietal ganglion projecting into the penis nerve were electrophysiologically and
      morphologically identified by simultaneously recording from the cell body
      intracellularly and the penis nerve extracellularly and subsequently filling them
      with an anterograde tracer and subjecting them to immunocytochemistry. This
      method has provided links between morphology, physiology, and the transmitter
      contents of these neurons.

PMID- 9619499
TI  - Changes in subcellular localization of metabotropic glutamate receptor subtypes
      during postnatal development of mouse thalamus.
AB  - High resolution immunoelectron microscopy was used to study subcellular
      localization patterns of three metabotropic glutamate receptor subtypes
      (mGluR1alpha, mGluR5, and mGluR2/3) during postnatal development of mouse ventral
      posterior (VP) thalamic nucleus. Immunoreactivity for all three mGluRs was
      detected from birth (postnatal day 0, P0), but mGluR1alpha showed dramatic
      changes in localization with age. In the first postnatal week, mGluR1alpha
      immunoreactivity was mainly found in proximal dendrites and somata and not
      usually associated with synaptic contacts. From the second postnatal week, it
      became concentrated in distal dendrites and preferentially associated with
      corticothalamic (RS) synapses. mGluR5 immunoreactivity was weaker than
      mGluR1alpha immunoreactivity at all postnatal ages and showed a similar change in
      subcellular distribution to that of mGluR1alpha. It was also localized in
      astrocytic processes. mGluR2/3 immunoreactivity was mainly localized in
      astrocytic processes surrounding neuronal somata and synapses and this pattern
      was consistently maintained through all postnatal ages. A small number of
      presynaptic axon terminals were labeled for mGluR2/3 immunoreactivity and formed
      asymmetrical synapses. This study demonstrates that Group I mGluR proteins
      (mGluR1alpha and mGluR5) become redistributed in association with the development
      of corticothalamic function as demonstrated physiologically, whereas Group II
      mGluR proteins (mGluR2/3) are mainly associated with neuroglia.

PMID- 9619500
TI  - Serotonin immunoreactivity in the central nervous system of the marine molluscs
      Pleurobranchaea californica and Tritonia diomedea.
AB  - The central nervous systems of the marine molluscs Pleurobranchaea californica
      (Opisthobranchia: Notaspidea) and Tritonia diomedea (Opisthobranchia:
      Nudibranchia) were examined for serotonin-immunoreactive (5-HT-IR) neurons and
      processes. Bilaterally paired clusters of 5-HT-IR neuron somata were distributed
      similarly in ganglia of the two species. In the cerebropleural ganglion complex,
      these were the metacerebral giant neurons (both species), a dorsal anterior
      cluster (Pleurobranchaea only), a dorsal medial cluster including identified
      neurons of the escape swimming network (both species), and a dorsal lateral
      cluster in the cerebropleural ganglion (Pleurobranchaea only). A ventral anterior
      cluster (both species) adjoined the metacerebral giant somata at the anterior
      ganglion edge. Pedal ganglia had the greatest number of 5-HT-IR somata, the
      majority located near the roots of the pedal commissure in both species. Most 5
      HT-IR neurons were on the dorsal surface of the pedal ganglia in Pleurobranchaea
      and were ventral in Tritonia. Neither the buccal ganglion of both species nor the
      visceral ganglion of Pleurobranchaea had 5-HT-IR somata. Afew asymmetrical 5-HT
      IR somata were found in cerebropleural and pedal ganglia in both species, always
      on the left side. The clustering of 5-HT-IR neurons, their diverse axon pathways,
      and the known physiologic properties of their identified members are consistent
      with a loosely organized arousal system of serotonergic neurons whose components
      can be generally or differentially active in expression of diverse behaviors.

PMID- 9619501
TI  - Microtubule disorientation and axonal swelling in unmyelinated sensory axons
      during vincristine-induced painful neuropathy in rat.
AB  - Neuropathic pain accompanies peripheral nerve injury following a variety of
      insults including metabolic disorders, traumatic injury, and exposure to
      neurotoxins such as vincristine and taxol. Vincristine, a microtubule
      depolymerizing drug, produces a peripheral neuropathy in humans that is
      accompanied by painful paresthesias and dysesthesias (Sandler et al., [1969]
      Neurology 19:367-374; Holland et al. [1973] Cancer Res. 33:1258-1264). The recent
      development of an animal model of vincristine-induced neuropathy provides an
      opportunity to investigate mechanisms underlying this form of neuropathic pain.
      Systemic vincristine (100 microg/kg) produces hyperalgesia to mechanical stimuli
      during the second week of administration, which persists for more than a week
      (Aley et al. [1996] Neuroscience 73:259-265). To test the hypothesis that changes
      in microtubule structure in nociceptive sensory neurons accompany vincristine
      induced hyperalgesia, we analyzed unmyelinated axons in saphenous nerves of
      vincristine-treated rats. This study constitutes the first quantitative
      ultrastructural analysis of the cytoskeleton of unmyelinated axons in peripheral
      nerve during neuropathic hyperalgesia. There was no evidence of unmyelinated
      fiber loss or a decrease in the number of microtubules per axons. There was,
      however, a significant decrease in microtubule density in unmyelinated axons from
      vincristine-treated rats. This decrease in microtubule density was due to a
      significant increase in the cross-sectional area of unmyelinated axons,
      suggesting swelling of axons. In addition, vincristine-treated axons had
      significantly fewer microtubules cut in cross-section and significantly more
      tangentially oriented microtubules per axon compared to controls. These results
      suggest that vincristine causes disorganization of the axonal microtubule
      cytoskeleton, as well as an increase in the caliber of unmyelinated sensory
      axons.

PMID- 9619502
TI  - Physiological properties of the Mauthner system in the adult zebrafish.
AB  - We investigated the morphological and electrophysiological properties of the
      Mauthner (M-) cell and its networks in the adult zebrafish (Danio rerio) in
      comparison with those in the goldfish (Carassius auratus). The zebrafish M-cell
      has an axon cap, a high resistivity structure which surrounds the initial segment
      of the M-axon, and accounts for an unusual amplification of the fields generated
      within and around it. Second, extra- and intracellular recordings were performed
      with microelectrodes. The resting potential was approximately -80 mV with an
      input resistance of approximately 0.42 M omega. The M-cell extracellular field
      was large (10-20 mV), close to the axon hillock, and the latency of antidromic
      spikes short (approximately 0.4 milliseconds), confirming a high conduction
      velocity in the M-axon. The extrinsic hyperpolarizing potential (EHP), which
      signals firing of presynaptic cells and collateral inhibition, was markedly lower
      at frequencies of spinal stimulation > approximately 5/second, suggesting an
      organization of the recurrent collateral network similar to that in the goldfish.
      Inhibitory postsynaptic potentials (IPSPs) were highly voltage-dependent; their
      decay time constant was increased by depolarizations. The presynaptic neurons
      which are numerous could be identified by their passive hyperpolarizing potential
      (PHP) produced by the M-spike current. Auditory responses, mediated via mixed
      synapses (electrical and chemical), had short delays and hence are well suited to
      trigger the escape reaction. The similarities of their properties indicate that
      the wealth of information generated over decades in the goldfish can be
      extrapolated to the zebrafish.

PMID- 9619503
TI  - A novel disruption of cortical development in p35(-/-) mice distinct from reeler.
AB  - The p35/cdk5 neuronal-specific kinase complex has been shown to play an important
      role in the laminar configuration of cortical neurons. Mice lacking either p35 or
      cdk5 exhibit a disrupted cortical lamination pattern. We showed previously that
      instead of the normal "inside-out" layering pattern of cortical neurons, cortical
      neurons are layered from "outside-in" in p35 mutant mice. To gain insight into
      the mechanisms that underlie these defects, we examined the organization of
      landmark structures formed during cortical development and the migratory behavior
      of p35(-/-) cortical neurons by using bromodeoxyuridine labeling. In the present
      study, we show that reelin localization in the marginal zone is normal in p35
      mutant mice. Furthermore, the preplate splits into the marginal zone and subplate
      properly, a developmental event that fails to occur in reeler mice. Finally, the
      migration of the earliest born cortical plate neurons is normal in p35 mutant
      mice; cortical neurons subsequently generated remain underneath these neurons.
      These data suggest that the p35/cdk5 kinase is required for cortical plate
      neurons to migrate past preexisting neurons and take up superficial positions to
      constitute the inside-outside layering order of cortical lamination.

PMID- 9619504
TI  - Light and electron microscopic distribution of the AMPA receptor subunit, GluR2,
      in the spinal cord of control and G86R mutant superoxide dismutase transgenic
      mice.
AB  - Excitotoxicity has been hypothesized to contribute to amyotrophic lateral
      sclerosis (ALS) neurodegeneration. The similar pattern of vulnerability in the
      spinal cord of mutant superoxide dismutase (SOD-1) transgenic mice and mice
      treated with excitotoxins supports a role for excitotoxicity in the mechanism of
      degeneration. The distribution of the alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) class of glutamate receptors (GluRs) with
      different calcium permeabilities has been proposed as an explanation for this
      differential vulnerability. GluR2 appears to be the dominant determinant of
      calcium permeability for AMPA receptors; thus, it is critical for their
      contribution to excitotoxic mechanisms. In this study, we investigate the
      distribution of GluR2 immunoreactivity in the spinal cord of control and SOD-1
      transgenic mice. GluR2 immunoreactivity is present equally within vulnerable
      neurons (i.e., motor neurons and calretinin-immunoreactive neurons) as well as
      nonvulnerable neurons (i.e., calbindin-immunoreactive neurons and dorsal horn
      neurons). In addition, postembedding immunoelectron microscopy reveals that GluR2
      is present in synapses of dorsal and ventral horn neurons and that the percentage
      of labeled synapses and numbers of immunogold particles per synapse do not vary
      between these spinal cord regions. Comparing control mice with SOD-1 transgenic
      mice, at both the light and the electron microscopic levels, the distribution and
      intensity of GluR2-immunoreactivity do not appear to be altered. These results
      suggest that the cellular and synaptic distribution of GluR2 is not a determinant
      of the selective vulnerability observed in SOD-1 transgenic mice or in ALS
      patients.

PMID- 9619506
TI  - Distamycin-stabilized antiparallel-parallel combination (APC) DNA.
AB  - The formation of Antiparallel-Parallel-Combination (APC) DNA, a liner duplex with
      a segment of parallel-stranded (ps) helix flanked by conventional B-DNA, was
      tested with a number of synthetic oligonucleotides. The groove-binding ligand
      distamycin A (DstA) was used to stabilize the ps segment comprising five A x T
      base pairs. Two drug molecules bound per APC, one in each of the two equivalent
      grooves characteristic of ps-DNA. APC-DNA, reference molecules and their
      complexes with DstA were analysed by several methods: circular dichroism and
      absorption spectroscopy, thermal denaturation, chemical modification, and
      molecular modeling. The dye binding stoichiometry differed significantly due to
      inherent structural differences in the groove geometries of ps-DNA (trans base
      pairs, similar grooves) and conventional antiparallel-stranded (aps) B-DNA (cis
      base pairs, distinct major and minor grooves). The data support the existence of
      APC folding in solution.

PMID- 9619505
TI  - Distributions of leptin receptor mRNA isoforms in the rat brain.
AB  - Leptin, secreted by white adipocytes, has profound feeding, metabolic, and
      neuroendocrine effects. Leptin acts on the brain, but the specific anatomic sites
      and pathways responsible for mediating these effects are still unclear. We have
      systematically examined distributions of mRNA of leptin receptor isoforms in the
      rat brain by using a probe specific for the long form and a probe recognizing all
      known forms of the leptin receptor. The mRNA for the long form of the receptor
      (OB-Rb) localized to selected nuclear groups in the rat brain. Within the
      hypothalamus, dense hybridization was observed in the arcuate, dorsomedial,
      ventromedial, and ventral premamillary nuclei. Within the dorsomedial nucleus,
      particularly intense hybridization was observed in the caudal regions of the
      nucleus ventral to the compact formation. Receptors were preferentially localized
      to the dorsomedial division of the ventromedial nucleus. Hybridization
      accumulated throughout the arcuate nucleus, extending from the retrochiasmatic
      region to the posterior periventricular region. Moderate hybridization was
      observed in the periventricular hypothalamic nucleus, lateral hypothalamic area,
      medial mammillary nucleus, posterior hypothalamic nucleus, nucleus of the lateral
      olfactory tract, and within substantia nigra pars compacta. Several thalamic
      nuclei were also found to contain dense hybridization. These groups included the
      mediodorsal, ventral anterior, ventral medial, submedial, ventral posterior, and
      lateral dorsal thalamic nuclei. Hybridization was also observed in the medial and
      lateral geniculate nuclei. Intense hybridization was observed in the Purkinje and
      granular cell layers of the cerebellum. A probe recognizing all known forms of
      the leptin receptor hybridized to all of these sites within the brain. In
      addition, intense hybridization was observed in the choroid plexus, meninges, and
      also surrounding blood vessels. These findings indicate that circulating leptin
      may act through hypothalamic nuclear groups involved in regulating feeding, body
      weight, and neuroendocrine function. The localization of leptin receptor mRNA in
      extrahypothalamic sites in the thalamus and cerebellum suggests that leptin may
      act on specific sensory and motor systems. Leptin receptors localized in
      nonneuronal cells in the meninges, choroid plexus, and blood vessels may be
      involved in transport of leptin into the brain and in the clearance of leptin
      from the cerebrospinal fluid.

PMID- 9619507
TI  - Homology model for the ligand-binding domain of the human estrogen receptor.
AB  - We have modeled the ligand-binding domain (LBD) of the human estrogen receptor
      protein (hER) by homology to the known crystal structure of the LBD of the alpha
      isoform of human retinoate-X receptor (hRX). Alignment of hER with members of the
      nuclear receptor superfamily defined probable secondary structures which we used
      to constrain backbone torsion angles and hydrogen bonds. From published studies
      we identified key interactions between hER and estradiol to use to dock the
      hormone in its ligand-binding pocket. Since the hRX crystal structure corresponds
      to the unliganded form of the LBD, we adopted the "mousetrap" mechanism proposed
      by Renaud et al to predict the structure of the E2-bound hER. Refinement by
      molecular dynamics and energy minimization gave a model which matches well the
      known facts about the estradiol phamacophore. It also provides a possible
      explanation for how hER discriminates between estradiol and testosterone.

PMID- 9619508
TI  - Three dimensional structure of the soybean agglutinin Gal/GalNAc complexes by
      homology modeling.
AB  - Complexes of soybean agglutinin (SBA) with galactose (Gal) and N-acetyl
      galactosamine (GalNAc) have been modeled based on its homology to erythrina
      corallodendron (EcorL) lectin. The three dimensional structure of SBA-Gal modeled
      with homology techniques agrees well with SBA-(beta-LacNAc)2Gal-R complex
      determined by X-ray crystallographic techniques at the beta-sheet regions and the
      regions where Ca2+ and Mn2+ ions bind. However, significant deviations have been
      observed between the modeled and the X-ray structures, particularly at the loop
      regions where the polypeptide chain could not be unequivocally traced in the X
      ray structure. The hydrogen bonding scheme, predicted from the homology model,
      shows that the invariant residues i.e. Asp, Gly, Asn, and aromatic residues (Phe)
      found in all other legume lectins, bind Gal, slightly in a different way than
      reported in X-ray structure of SBA-pentasaccharide complex. The higher binding
      affinity of GalNAc over Gal to SBA is due to additional hydrophobic interactions
      with Tyr107 rather than a hydrogen bond between N-acetamide group of the sugar
      and the side chain of Asp88 as suggested from X-ray crystal structure studies.
      Our modeling also suggest that the variation in the length of the loop D observed
      among galactose binding legume lectins may not have any effect on the binding of
      sugar at the monosaccharide specific site of the lectins. Soybean agglutinin
      (SBA) is a member of the leguminous family of lectins. They generally possess a
      single carbohydrate binding site, besides the tightly bound Ca2+ and Mn2+ ions
      which are required for their carbohydrate binding activity. They possess a high
      degree of sequence homology and about 50% of the amino acid residues are
      invariant. Some of these invariant amino acid residues are involved in the
      binding of sugar moieties and in metal ion coordination. X-ray crystallographic
      studies showed that their three-dimensional structures are very similar, though
      they differ in their carbohydrate binding specificity (1-6). Three of the
      invariant residues Asp, Gly, and Asn, besides an aromatic residue (Phe or Tyr),
      are involved in carbohydrate binding. Independent of their sugar specificity,
      these four residues in legume lectins provide the basic frame for the sugar to
      bind.

PMID- 9619509
TI  - Structure and dynamics of elastin building blocks. Boc-LG-OEt, Boc-VGG-OH.
AB  - Short di- and tripeptides such as Boc-LG-OEt, Boc-VG-OEt and Boc-VGG-OH,
      corresponding to abundant repetitive sequences in elastin, have been extensively
      studied both in solid state, by X-ray diffraction, and in solution by circular
      dicroism and nuclear magnetic resonance. Furthermore, theoretical procedures such
      as simulated annealing and molecular dynamics were also performed on these
      peptides. In general, the results indicate that no one single structure (be
      folded or extended) could be representative for these sequences in the protein,
      but rather that a multiplicity of interconverting conformers, ranging from folded
      to extended structures, should be considered. In any case, these structures, e.g.
      beta-turns, polyglycine II and beta-conformations, are those previously suggested
      to participate to conformational equilibria of elastin.

PMID- 9619510
TI  - Variability analysis of HIV-1 gp120 V3 region: IV. Distribution functions for
      intra- and inter-subtype amino acid hamming distances.
AB  - Distribution functions for intra- and inter- HIV-1 V3-loop subtypes amino acid
      Hamming distances were calculated (850 V3-loop sequences from the Los Alamos HIV
      1 Database (1996) were used). These functions have pronounced bell-like shape.
      Such shapes of the histograms for HIV-1 V3 intra- and inter-subtype distriutions
      are discussed to confirm the applicability of different hierarchical cluster
      procedures for HIV-1 V3 classification. Two-mode distribution for the subtype E
      could sertificate that this subtype includes two thinner taxons.

PMID- 9619511
TI  - One-parameter discrete model of the genetic diversity.
AB  - One-parameter discrete model estimating genetic distance between precursor and
      descendant nucleotide sequences after several steps of substitution acts is
      developed. This model based on the previously introduced symbol sequences
      enumeration procedure (M.Y. Shchelkanov, A.N. Yudin, A.V. Antonov, N.S. Starikov,
      A.A. Vedenov, E.V. Karamov, J. Biomol. Struct. Dyn. 15, 231-241 (1997)) differs
      from Jukes-Cantor and Kimura models by the absence of the assumptions usual for
      continuous Markov's processes. Formula obtained with the help of our model are
      more preferable since they take into account multiple repetition substitution
      ability and they are correct in the entire admissible range of parameters.

PMID- 9619512
TI  - Effect of selective substitution of 5-bromocytosine on conformation of DNA triple
      helices.
AB  - Three triplex DNAs containing 5-bromocytosine[BrC] were studied by vibrational
      spectroscopy and molecular modelling. Firstly, three oligodeoxypyrimidines of 5'
      (TC)3-T4-(BrCT)3 [CBrC], 5'-(TBrC)3-T4-(CT)3 [BrCC] and 5'-(TBrC)3-T4-(BrCT)3
      [BrCBrC] were synthesized and then reacted with an oligodeoxypurine of 5'-(AG)3
      at pH=4.5 in phosphate buffer respectively to form three comparative hairpin
      triplex named CY,YC and YY. The results of FT-Raman and IR revealed that YY is
      almost in A-like form, CY and YC are combinations of A-like form and B-like form,
      but A-form dominates in CY while B-form is equivalent as A-form in YC. The result
      is consistent with the theoretical analysis.

PMID- 9619513
TI  - The intrinsic curvature of a 51 bp K-DNA fragment of Leishmania tarentolae: a
      molecular model.
AB  - DNA intrinsic structure and curvature is a subject of debate because of the
      importance of these attributes in processes such as DNA packaging, transcription,
      and gene regulation. X-ray crystallography of DNA single crystals has provided a
      wealth of information about the local, short range conformational features of
      DNA. On the other hand, gel electrophoresis analysis of DNA has not only
      uncovered the macroscopic curvature of DNA but it also provides most of the
      available data on DNA intrinsic curvature. However, gel electrophoresis can not
      identify features of DNA structure at the nucleotide or atomic level. In order to
      address the problem of DNA intrinsic curvature in an attempt to bridge the gap
      between X-ray crystallography and gel electrophoresis, we use the computational
      method of molecular dynamics (MD). In this study, we report the results of 2.0 ns
      MD simulations on a 51 bp fragment of the K-DNA of Leishmania tarentolae
      containing several A-tracts. The K-DNA double helix is very stable and remains in
      an intermediate state between the canonical A and B forms of the duplex. The
      magnitude of global curvature (75 degrees) agrees well with the experimental
      estimate (72 degrees) available. Analysis of local (every base triplet) and
      sublocal (every helix turn) curvature shows that the 51 bp K-DNA fragment has
      curvature features also present in the Wedge, Junction and Calladine's models of
      DNA intrinsic curvature. We further characterize the flexibility of individual
      nucleotides in the molecule and find the sugar flexibility within the A-tracts to
      be strongly correlated with the pattern of A-tract cleavage by the hydroxyl
      radical. Differential curvature and flexibility at the 5' and 3'junctions between
      A-tracts and general-sequence DNA are found to modulate the global curvature of
      the K-DNA fragment.

PMID- 9619514
TI  - Conformational study of DNA-RNA duplexes containing MMI substituted
      phosphodiester linkages by FTIR spectroscopy.
AB  - Six methylene(methylimino) (MMI, Bhat et al. J. Org. Chem., 61, 8186, 1996)
      linked oligonucleotides a-f (* = MMI linkage; 5'-GCGT*TT*TT*TT*TT*TGCG-3')
      containing various combinations of 2'-O-methyl and 2'-fluoro substituent were
      synthesized as a model to study the global conformational change upon
      hybridization to the complement RNA. Fourier transform infrared (FTIR)
      spectroscopic technique has been used to study and compare the influence of these
      modifications on the solution conformation of 2'-modified MMI DNA-RNA duplexes.
      FTIR analysis of the single-stranded RNA (5'-CGCAAAAAAAAAACGC-3') and the
      modified oligonucleotides a-f showed that all sugar residues adopted a C3'-endo
      conformation (North-type). Stable duplexes were formed when oligonucleotides a-f
      were hybridized to the complement RNA. These duplexes retained the original C3'
      endo conformation for all sugar residues, hallmark of an A-form of duplex. We
      postulate that the observed preorganization of the sugar residues and
      oligonucleotides containing 2'-modified MMI modifications may play an important
      role in both improving the recognition of RNA target and enhancing the stability
      of duplex formation with RNA.

PMID- 9619515
TI  - Nucleosome units and hidden periodicities in DNA sequences.
AB  - The relationship between the hidden periodicities in DNA sequences and the
      nucleosome units is investigated. It is shown that in the vicinity of lengths of
      about 200 bases there are statistically significant periodicities which remain
      approximately universal for exon-intron sequences both in the different genes and
      the different eukaryotic species. The additional analysis displays, nevertheless,
      that these approximately coincident universal periodicities can be generated by a
      variety of mechanisms. The relevance of the features observed to the structure of
      chromatin is discussed.

PMID- 9619516
TI  - Circular superhelical DNA complexes with synthetic oligopeptide: unusual compact
      structures and influence of bent sequences on the results of compaction.
AB  - The organization of synthetic oligopeptide trivaline (1) complexes with four
      types of circular superhelical DNA preparations was studied by electron
      microscopy. The DNA molecules in the preparations investigated had different
      sizes ranging from 2.9 kb to 21.0 kb. Two plasmids contained bent DNA sequences
      from minicircles of kinetoplast DNA of Leishmania gymnodactili and Trypanosoma
      boissoni. The main structures in all preparations observed were circular compact
      particles which coincide in their appearance and compaction coefficient (3,5-3,7)
      with triple rings described earlier. But along with triple rings the new types of
      compact structures were observed having the shape of a ring with attached rod or
      the shape of two compact rings attached to each other by a region of compact
      fiber. The latter structures could be observed in significant quantities in case
      of DNA preparations longer than 10 kb. The conclusions can be made that due to
      TVP stimulated compaction of circular DNA molecules compact fibers containing
      both two or three DNA duplexes arranged side by side can be formed. It is shown
      that presence of bent DNA sequences stimulates the formation of structures
      containing more than one triple ring. It demonstrates the possibility of the
      primary DNA structure influence on the compaction process in case of the circular
      molecules. The new ways of circular DNA folding described can be of importance
      for understanding of DNA organization in different cell structures.

PMID- 9619517
TI  - A fluorescence spectroscopic and molecular dynamics study of bis-ANS/protein
      interaction.
AB  - Despite emergence of bis-ANS as a major fluorescence probe of proteins structure,
      conformational and spectroscopic properties of protein/bis-ANS complexes remains
      largely unexplored. We have shown that fluorescence polarization of both ANS and
      bis-ANS is excitation wavelength dependent and this is a property of all protein
      ANS/bis-ANS complexes studied. Bis-ANS excitation maximum is always more red
      shifted than the corresponding ANS complex. Even when corrected for the red
      shift, the bis-ANS complexes in some, but not all, cases show only a little
      lowering of polarization, suggesting modest additional depolarization in bis-ANS
      compared to ANS. Calculation of energy migration rate between the two rings
      suggests that energy migration rate should be high at all values of the naphthyl
      naphthyl dihedral angle. Although, Molecular mechanics and dynamics calculations
      show that the lowest energy conformation of bis-ANS is when the two naphthalene
      rings are roughly perpendicular to each other, due to rapid energy migration this
      conformation should lead to dramatic lowering of emission anisotropy, unlike what
      is observed. Salt and temperature dependence of bis-ANS/protein interaction
      suggests little ionic interaction and pre-dominant interaction through
      hydrophobic aromatic rings. We conclude that bis-ANS binds to proteins through
      interaction with the aromatic rings and with two rings nearly parallel to each
      other.

PMID- 9619518
TI  - A study of metalloporphyrin-polynucleotide interactions by microcalorimetry and
      circular dichroism.
AB  - In this paper we examine the interactions of Calf Thymus DNA and the model
      polynucleotides poly(dA).poly(dT), poly(dAdT)2 and poly(dG.dC)2 with a group of
      metalloporphyrins derived from the freebase porphyrin tetrakis(4-N
      methylpyridyl)porphine, H2(TMpy-P4), by means of ultraviolet absorption
      spectroscopy, circular dichroism spectroscopy and microcalorimetry. We have
      studied the interactions of the copper, cobalt, nickel and zinc derivatives of
      H2(TMpy-P4) in addition to the free base porphyrin itself. We have found strong
      evidence for an external self-stacking interaction of the Cu(TMpy-P4) and Zn(TMpy
      P4) derivatives with poly(dA).poly(dT) and poly(dAdT)2 even at low concentrations
      of porphyrin, and all of the porphyrin derivatives studied appear to display such
      a self-stacking in interaction with poly(dA.dT)2 at sufficiently high ratios of
      porphyrin to polynucleotide.

PMID- 9619519
TI  - A molecular dynamics computer simulation study of nucleotide analogues.
      Comparison of the hydration pattern of dithymidine phosphate with those of the
      dithymidine methylphosphonate diastereomers.
AB  - The hydration pattern of thymidyl(3'->5') thymidine 1 and those of Rp and Sp
      diastereomers of the corresponding methylphosphonate analogue 2, have been
      studied using Molecular Dynamics (MD) computer simulation. It was found that the
      methylphosphonate modification leads to significant changes in the coordination
      of water molecules around the internucleotidic linkage and these, in turn, affect
      the hydration pattern of other parts of the molecule. The most notable
      differences between Rp and Sp diastereomers 2a and 2b were found to occur at the
      deoxyribose moieties of the nucleosid-5'-yl units.

PMID- 9619520
TI  - Molecular dynamics simulation of colchicinoids.
AB  - Colchicine, a tricyclic alkaloid, has a remarkable range of biological
      activities. It binds with tubulin and prevents the formation of microtubules.
      This compound consists of a six membered aromatic ring (A ring), a seven membered
      troponoid ring (C ring) and another seven membered aliphatic ring (B ring). Using
      molecular mechanics and molecular dynamics simulations as tools, conformational
      analysis of colchicine and its several important analogs were done. Molecular
      mechanics studies show that conformational space of these molecules have one low
      energy region. Taking the low energy minima as the starting conformation,
      molecular dynamics simulation for 100 pico seconds is done for each of the
      analogs and molecular dynamics simulation in solution is done for three
      representative compounds colchicine,isocolchicine and A-C compound. Internal
      coordinate trajectories show that the value of the dihedral angle C9-C7-C1-C14
      (phi), (C7-C1 bond connects the A and C ring), is within 40 degrees to 50 degrees
      for all the compounds with fluctuations less than 15 degrees. These calculations
      indicate that there is an overall similarity in the dynamically averaged
      structure of all the drugs. The A ring and B ring of the compounds are more or
      less rigid. The C ring is somewhat flexible, the average conformation and
      motional properties show overall similarity. The potential energy curve and
      dynamics behaviour of colchicine and isocolchicine suggests that the difference
      in binding property of colchine and isocolchicine may originate from the
      positional difference of carbonyl oxygen and methoxy group of C ring, which is
      the only difference in the structures of the two compounds and this has no effect
      on the motional property and average conformations of these two compounds. From
      our study it is proposed that the movements occuring at various positions of the
      drug molecules are significantly correlated. It is suggested that such correlated
      motion may play an important role in the biological property of these compounds.

PMID- 9619521
TI  - Incidence of chromosomal aberrations in children born after assisted reproduction
      through intracytoplasmic sperm injection.

PMID- 9619522
TI  - Episcientific aspects of the epigenetic factors in artificial procreation.

PMID- 9619523
TI  - No impact of cryopreservation and thawing on embryo developmental potential--one
      more example for the problems of retrospective, non-controlled data.

PMID- 9619524
TI  - Aspects of epigenetic factors in artificial procreation.

PMID- 9619525
TI  - Mullerian anomalies.

PMID- 9619526
TI  - Effects of long-term low-dose mifepristone on reproductive function in women.
AB  - Low-dose antiprogestin administration has been proposed as a new contraceptive
      modality to interference with endometrial receptivity without disturbing ovarian
      function. The effects of 1 mg/day mifepristone for 150 days on the menstrual
      cycle were assessed in 21 surgically sterilized women. The aim was to study each
      woman for one control cycle and during months 1, 3 and 5 of treatment. Ovulation,
      endometrial thickness, serum oestradiol and progesterone, urinary luteinizing
      hormone, endometrial morphology and cervical mucus were assessed. Luteal phase
      progesterone concentrations were observed in 36 of the 60 treated months assessed
      and less frequently as treatment progressed. The bleeding pattern was regular in
      most biphasic cycles, while prolonged interbleeding intervals or no bleeding were
      associated with monophasic cycles. Altered endometrial morphology was found in
      all cases irrespective of the occurrence of luteal activity. Increased
      endometrial thickness and dilated glands were observed in 25 and 34% respectively
      of the monophasic cycles. Mifepristone, 1 mg/day, interferes with endometrial
      development while allowing the occurrence of biphasic ovarian cycles and regular
      bleeding. However, it also prevents ovarian cyclicity in a high proportion of
      treated months, and this is associated with increased endometrial growth in some
      women, which may be of concern.

PMID- 9619527
TI  - 11Beta-hydroxysteroid dehydrogenase type 2 in human pregnancy and reduced
      expression in intrauterine growth restriction.
AB  - The type 2 isoform of 11beta-hydroxysteroid dehydrogenase (11beta-HSD2), which
      inactivates cortisol (F) to cortisone (E), has been suggested to play a role in
      the ontogeny of the fetal pituitary-adrenal axis and also protect the developing
      fetus from the deleterious effects of circulating maternal glucocorticoids. The
      abundance of 11beta-HSD2 in the placenta and other fetal tissues was inferred
      from the F/E ratio in 17 term deliveries in both umbilical arterial (1.73 +/-
      0.24, mean +/- SE) and umbilical venous blood (1.16 +/- 0.14) compared with adult
      peripheral venous blood (7.76 +/- 0.57, n = 70). Using sensitive assays for
      11beta-HSD2 and an in-house human 11beta-HSD2 antibody, the expression and
      activity of this enzyme in fresh frozen human placenta increased progressively
      from first (8-12 weeks, n = 16) and second (13-20 weeks, n = 9) to third
      trimester (term) pregnancies (39-40 weeks, n = 50). Placental 11beta-HSD2
      activity was significantly reduced in deliveries complicated by intrauterine
      growth restriction (IUGR) [25-36 weeks, n = 12, activity 380 pmol/mg/h median
      (225-671; 95% confidence interval)], compared with the term deliveries [888 (725
      1362)] and with appropriately grown pre-term deliveries [27-36 weeks, n = 14,
      activity 810 (585-1269)], P < 0.05. In human pregnancy placental 11beta-HSD2
      activity increases markedly in the third trimester of pregnancy at a time when
      maternal circulating levels of glucocorticoid are rising. The finding of
      attenuated placental 11beta-HSD2 activity in IUGR suggests that glucocorticoids
      may, in part, contribute to impaired fetal growth and that this is closely
      controlled in normal gestation through placental 11beta-HSD2 expression.

PMID- 9619528
TI  - Detection of chromosomal aberration in fetuses arising from recurrent spontaneous
      abortion by comparative genomic hybridization.
AB  - Chromosomal abnormalities (mostly aneuploidy) account for approximately 50% of
      fetal losses in the first 8-15 weeks of gestation. Cytogenetic analysis of
      aborted fetal material depends on conventional tissue culturing and karyotyping.
      This technique is laborious and is subject to problems including external
      contamination, culture failure and selective growth of maternal cells.
      Comparative genomic hybridization (CGH) was used to determine the chromosomal
      constitution of 27 fetuses arising from recurrent spontaneous abortion. In 12
      samples, the CGH results were compared to the results obtained by conventional
      cytogenetic techniques. Correlation was found in 75% of samples. Overall, CGH
      detected chromosomal abnormalities in 48% of the samples, including trisomies,
      monosomies, and partial chromosome gains and losses. The preliminary data in this
      study show that CGH can be added, at least as a complementary method, to the
      traditional cytogenetic techniques used in the investigation of recurrent
      spontaneous abortions.

PMID- 9619530
TI  - Utero-ovarian arterial blood flow and hormonal profile in patients with
      polycystic ovary syndrome.
AB  - Utero-ovarian arterial blood flow and hormonal profile were evaluated in 20
      patients with polycystic ovary syndrome (PCOS) and in 22 patients with normal
      menstrual cycle (NMC) undergoing in-vitro fertilization (IVF) treatment. In this
      controlled prospective clinical study the vascular impedance in the utero-ovarian
      arteries was measured in both groups on days 4, 13, 22 [introduction of
      gonadotrophin releasing hormone agonist (GnRHa) administration], 36 (after the 14
      day GnRHa administration) and on the day of human chorionic gonadotrophin (HCG)
      administration. Simultaneously, serum concentrations of luteinizing hormone (LH),
      follicle stimulating hormone (FSH), oestradiol, androstendione and sex hormone
      binding globulin (SHBG) were determined. In the PCOS group significantly (P <
      0.05) higher concentrations of FSH and LH were found on day 22, whereas the
      excess of androstendione production and lower SHBG values were registered
      throughout the studied cycles. Also, no effect of the 14 day GnRHa administration
      on the androstendione discharge was registered. In both groups the serum LH
      concentration decreased significantly (P < 0.05); however, the value remained
      significantly (P < 0.05) higher in the PCOS group. In the PCOS group no changes
      regarding the vascular impedance in the uterine artery were registered in the
      phase of the cycle preceding the GnRHa administration. The resistance index (RI)
      on day 22 of the cycle was 0.86 in the PCOS and 0.82 in the NMC group. In the NMC
      group the active ovary showed dramatic changes during the cycle, with vascular
      impedance almost constant throughout the cycle in the inactive ovary. In the PCOS
      group the vascular impedance to ovarian arterial blood flow in both ovaries was
      similar to that in inactive ovaries in the NMC group. After the 14 day GnRHa
      administration the utero-ovarian vascular impedance was high in both groups with
      changes registered only in the NMC group, as the PCOS patients exhibited maximal
      vascular impedance throughout the cycle. On the day of HCG administration strong
      negative correlation between the vascular impedance in the uterine artery and the
      serum oestradiol concentration in stimulated cycles was found in both groups, but
      not in anovulatory PCOS patients. As in PCOS patients the utero-ovarian vascular
      impedance was raised throughout the cycle we concluded that the 14 day GnRHa
      administration neither affected the utero-ovarian arterial blood flow nor
      suppressed the androstendione discharge.

PMID- 9619529
TI  - Induction of the endogenous gonadotrophin surge for oocyte maturation with intra
      nasal gonadotrophin-releasing hormone analogue (buserelin): effective minimal
      dose.
AB  - From 1985-1987, a total of 34 couples undergoing superovulation for a single in
      vitro fertilization (IVF) cycle with clomiphene citrate and purified follicle
      stimulating hormone (FSH) or human menopausal gonadotrophin (HMG) were randomly
      allocated doses of intra-nasal buserelin to induce an endogenous gonadotrophin
      surge, prior to oocyte collection. The doses ranged from a single 25 microg dose
      to 100 microg every 4 h for 20 h. In three cycles the treatment was abandoned
      because of a poor ovarian response. In the remaining 31 cycles buserelin was
      given to induce the endogenous gonadotrophin surge, but there was evidence of
      premature luteinization in eight cycles and a premature gonadotrophin surge in
      four cycles. Although a single dose as low as 40 microg induced a surge and
      resulted in a pregnancy, a single dose of 50 microg proved the most effective
      minimal dose consistently to induce a gonadotrophin surge and oocyte maturation.
      Recent reports using gonadotrophin-releasing hormone (GnRH) analogues to induce a
      gonadotrophin surge has prompted publication of this previously unpublished data.

PMID- 9619531
TI  - Prolonged inhibition of presynaptic catecholamine synthesis does not alter leptin
      secretion in normal-weight men and women.
AB  - Leptin has been called a hormone of reproduction, and seems to link fat and
      fertility. It has been speculated that the neurotransmitter norepinephrine (NE)
      (noradrenaline), possibly via the sympathetic nervous system, may represent the
      afferent signal which modulates leptin release from adipocytes. The purpose of
      this study was to produce a state of decreased sympathetic output by using the
      catecholamine synthesis inhibitor alpha-methyl-para-tyrosine (AMPT), in order to
      study the effect of this compound on the secretion of leptin from fat cells. Ten
      subjects (five women and five men) received a total of 5 x 1 g doses of AMPT or 5
      x 50 mg promethazine (active placebo) over a 26 h period, separated by 4-6 weeks
      using a randomized, double-blind, placebo-controlled, cross-over design. Blood
      samples for hormone measurements were obtained over 24 h (18 time points) on day
      2 of each experiment. Urinary measurement of the NE metabolite 3-methoxy-4
      hydroxyphenylglycol (MHPG) on study day 2 served as a marker of the effectiveness
      of AMPT as an inhibitor of NE synthesis. The daily excretion of this metabolite
      decreased from 1.56 +/- 0.22 mg in the placebo experiment to 0.53 +/- 0.1 mg in
      the active experiment (P < 0.05). Plasma leptin concentrations measured in the
      control group in women and men were similar to those reported previously in lean
      subjects with a body mass index < 27.5 kg/m2. Leptin concentrations in women were
      3-fold higher than in men. Leptin is secreted in a circadian rhythm in both sexes
      with an increase of nocturnal concentrations by approximately 50%. Two-way
      analysis of variance reveals no significant difference in leptin secretion
      between the control and active groups in women and men. In summary, preliminary
      results do not support the hypothesis that NE represents the afferent signal from
      the central nervous system which modulates leptin release from adipocytes in the
      human. Further studies are needed to define the role of the sympathetic nervous
      system as well as NE in the regulation of leptin secretion and its involvement in
      obesity and reproduction.

PMID- 9619532
TI  - The expression of the urinary forms of human luteinizing hormone beta fragment in
      various populations as assessed by a specific immunoradiometric assay.
AB  - Human gonadotrophins undergo metabolic transformations which result in the
      presence of several smaller, structurally and immunologically related forms of
      gonadotrophins in the urine. For luteinizing hormone (LH), a beta core fragment
      (LHbeta cf) has been isolated from the pituitary and characterized. The
      corresponding urinary fragment is inferred from mass spectral and immunochemical
      analysis of chromatographically separated urinary forms. Physicochemical
      characteristics, primarily mass spectral and chromatographic, indicate that the
      pituitary and urinary forms of LHbeta cf have a different structure, probably in
      the carbohydrate moieties. This communication characterizes the expression of
      LHbeta cf in the urine of both reproductive and post-reproductive age women and
      in men, employing assays highly specific for the pituitary form of the fragment.
      It was found that LHbeta cf is the predominant LH associated molecular form in
      the urine during peri-ovulatory period, peaking 1-3 days later than intact LH and
      reaching a concentration of approximately 600 fmol/mg creatinine, 7-fold higher
      than either LH or LH free beta subunit. Corresponding concentrations of human
      chorionic gonadotrophin (HCG) beta cf were <1% that of LHbeta cf. LHbeta cf cross
      reaction with some LH or LHbeta monoclonal antibodies may well interfere with the
      accurate estimation of the day of the LH surge when urinary tests are utilized.

PMID- 9619533
TI  - A prospective randomized study to assess the clinical efficacy of gonadotrophins
      administered subcutaneously and intramuscularly.
AB  - The purpose of this study was to compare the clinical efficacy of gonadotrophins
      administered s.c. or i.m., in a prospective randomized study of women undergoing
      in-vitro fertilization (IVF) treatment at a tertiary referral centre. In all, 71
      patients undergoing a total of 162 IVF treatment cycles were randomized to
      receive either s.c. (n = 41) or i.m. (n = 30) administration of gonadotrophins.
      Up to three cycles of IVF were assessed for each patient. The main outcome
      measures were the number of oocytes retrieved, the total amount of gonadotrophins
      used, the number of follicles recruited and the cumulative pregnancy and live
      birth rates. The mean number of oocytes retrieved was 10.5 for each group. The
      number of days of stimulation was significantly shorter for the s.c. group (11.7
      +/- 1.9 days, mean +/- SD) than the i.m. group (12.6 +/- 2.3 days). The
      cumulative conception and live birth rates after three cycles of treatment were
      similar between the two groups. Our results suggest that the clinical efficacy of
      s.c. and i.m. administration of gonadotrophins is comparable. Both routes are
      well tolerated by patients.

PMID- 9619534
TI  - Activin B: detection by an immunoenzymometric assay in human serum during ovarian
      stimulation and late pregnancy.
AB  - A recently developed immunoenzymometric assay for activin B has been
      characterized further by measurement during ovarian stimulation and pregnancy.
      The assay is based on a monoclonal anti-peptide antibody, anti-betaB(101-115). In
      addition to quantitative analyses, the antibody has been used for
      immunohistochemical localization of the activin betaB-subunit in human term
      placenta. Serum samples obtained from patients suffering from tubal factor
      infertility who were admitted for in-vitro fertilization (IVF) treatment
      protocols or from patients with proven fertility who were admitted for
      laparoscopic tubal ligation were collected. The aim was to correlate serum
      activin B concentrations with other parameters during IVF and with phases of the
      menstrual cycle. Serum samples obtained from healthy pregnant volunteers were
      studied to correlate activin B concentrations with clinical parameters. During
      the IVF treatment protocols, activin B was detectable in all patients studied,
      and a significant negative correlation was observed between serum activin B and
      oestradiol concentrations. On the other hand, no significant difference was
      observed in activin B concentrations when serum samples obtained from patients at
      different phases of the menstrual cycle were compared, and low concentrations of
      activin B were observed in the samples obtained from these patients. During
      pregnancy, a positive correlation was observed between serum activin B
      concentrations and gestational age. In immunohistochemical analyses of human
      placental tissue obtained from healthy parturients, the activin betaB-subunit was
      present in trophoblast, amniotic epithelial and Hofbauer cells. The results
      suggest a potential clinical application in female reproductive medicine for
      serum activin B measurements.

PMID- 9619535
TI  - Acute insulin response to intravenous glucagon in polycystic ovary syndrome.
AB  - In order to evaluate the acute insulin response after i.v. injection of glucagon
      in polycystic ovary syndrome (PCOS), 35 women affected by PCOS and 11 normo
      ovulatory controls underwent a 75 g oral glucose tolerance test (OGTT) and, 2
      days later, a glucagon test (1 mg i.v.). Patients were analysed according to
      their degree of obesity; the insulin release after glucagon injection for lean
      PCOS subjects and control women was not statistically significantly different.
      Conversely obese PCOS patients had higher insulin secretion after both i.v.
      glucagon and OGTT when compared to the other groups. Moreover the insulin
      secretory patterns were heterogeneously represented in lean and obese PCOS women.
      When the patients were analysed according to their insulinaemic response to OGTT,
      normoinsulinaemic PCOS women and control subjects had a similar insulin response
      to i.v. glucagon whereas the hyperinsulinaemic PCOS group had a higher insulin
      response (P < 0.0001). Moreover, a highly significant relationship was found
      between the insulin response to OGTT and to glucagon administration in the PCOS
      population (P < 0.0001; r = 0.73), which was maintained also after controlling
      for obesity. Our results are consistent with the hypothesis that PCOS patients
      could have an insulin hyper-response to glucagon administration, that is
      partially independent from obesity and related to their insulinaemic status.
      Moreover, the glucagon test could represent an effective alternative to OGTT in
      screening insulin disorders of PCOS patients (at least in the absence of other
      risk factors), due to its reliability, simplicity, and speed of performance.

PMID- 9619536
TI  - Two distinct two-step ranks of progesterone stimulation after three different
      levels of oestrogen priming. Effect on induction of luteinizing hormone surges in
      young and climacteric women.
AB  - Age and menopausal status were evaluated as potential modulators of the
      progesterone action in the initiation of the mid-cycle luteinizing hormone (LH)
      surge in women. Three distinct levels of oestradiol priming were used, in
      combination with two different two-step ranks of progesterone stimulation (10/25
      mg and 25/50 mg i.m. injections of progesterone in oil, over 2 consecutive days)
      in two groups of women, ten premenopausals, aged between 18 and 25 years, and 14
      postmenopausals, aged between 48 and 57 years. The low, moderate and high levels
      of oestradiol priming were defined in the premenopausal group by days 5 and 9 of
      the cycle, and 0.4 mg transdermal oestradiol applied in the early follicular
      phase respectively. The corresponding situation in the postmenopausal women was
      defined by the absence of treatment, 0.1 mg transdermal oestradiol, and 0.4 mg
      transdermal oestradiol respectively. The oestradiol patches were maintained for 5
      days, and the first progesterone dose administered on day 3 of treatment.
      Unambiguous LH surges, detected in serum and urine, were restricted to the
      protocols using 0.4 mg oestradiol in both groups, with an onset soon after
      progesterone administration. The surge was higher in the postmenopausal group in
      serum and urine. The percentage LH increase above baseline, however, was higher
      in the premenopausal women. The dose of progesterone did not result in any
      changes in pituitary LH release. Therefore, the oestradiol threshold for the
      progesterone stimulatory effect on LH release was similar in both groups. The
      postmenopausal women did not yield defective LH surges when adequately primed
      with oestradiol and progesterone.

PMID- 9619537
TI  - Unilateral hydrothorax as a sole and recurrent manifestation of ovarian
      hyperstimulation syndrome following in-vitro fertilization.
AB  - Acute unilateral hydrothorax may appear as the sole extra-ovarian expression of
      severe ovarian hyperstimulation syndrome (OHSS). This case report describes two
      such cases, in one of which the patient developed this rare complication in two
      consecutive ovarian stimulation cycles. Awareness is needed for the timely and
      appropriate diagnosis of this rare complication that occurs 9-14 days following
      human chorionic gonadotrophin (HCG) administration and may recur in consecutive
      stimulation cycles. Thoracocentesis and fluid balance maintenance are efficient
      modes of therapy resulting in good outcome.

PMID- 9619538
TI  - Attitudes about genetic risk of couples undergoing in-vitro fertilization.
AB  - Many couples undergoing in-vitro fertilization (IVF) are at a higher risk of
      having a child with a genetic abnormality. In a sample of 55 consecutive couples
      starting IVF, only 33% had no genetic risk factor. The most common genetic risks
      were advanced maternal age and possible abnormalities associated with severe male
      infertility. Despite education on these risks, 71% of couples had no interest in
      receiving formal genetic counselling. Only 14% of couples at risk would consider
      using a gamete donor to avoid transmitting a genetic disorder to a child. The
      triple test to screen for fetal abnormalities was acceptable to 82% of couples,
      but only 47% planned to have amniocentesis or chorionic villi sampling. Couples
      were significantly more likely to opt for prenatal testing if they would consider
      terminating a pregnancy should the fetus have a severe genetic abnormality (P <
      0.01). Roman Catholic couples tended to have more conservative attitudes about
      pregnancy termination. Socio-economic status and whether the infertility factor
      was male or female were not predictors of a couple's attitudes.

PMID- 9619539
TI  - Surgical complications of diagnostic and operative gynaecological laparoscopy: a
      series of 29,966 cases.
AB  - A multicentre study was carried out in seven top French centres for laparoscopic
      gynaecological surgery. This series covers a period of 9 years, in which 29,966
      diagnostic and operative laparoscopic operations were performed. The risk of
      complications has been assessed according to the complexity of the laparoscopic
      procedure in question. The means of diagnosis and treatment of the complications
      have been analysed, together with the importance of the surgeon's degree of
      experience. The mortality rate was 3.33 per 100,000 laparoscopies. The overall
      complication rate was 4.64 per 1000 laparoscopies (n = 139). The rate of
      complications requiring laparotomy was 3.20 per 1000 (n = 96). The complication
      rate was significantly correlated with the complexity of the laparoscopic
      procedure (P = 0.0001). One in three complications (34.1%; n = 43) occurred while
      setting up for laparoscopy, and one in four (28.6%) were not diagnosed during the
      operation. As new indications for laparoscopic surgery in gynaecology have
      appeared, there has been a parallel and statistically significant increase in the
      rate of urological complications (P = 0.001). Increased experience by the
      surgeons has had three consequences: a statistically significant drop in the
      number of bowel injuries (P = 0.0003), a drop in the rate of complications
      requiring laparotomy for those laparoscopic surgical procedures that are well
      defined (P = 0.01), and a change in the way complications are treated, with a
      significant increase in the proportion of incidents treated by laparoscopy (P =
      0.0001).

PMID- 9619540
TI  - Abdominal myomectomy for infertility: a comprehensive review.
AB  - To obtain estimates of the effect of abdominal myomectomy on infertility,
      information from studies published in the English language literature between
      1982 and 1996 was retrieved. Articles were identified through hand and
      computerized searches using Medline. A total of 27 trials, all published in peer
      reviewed journals, was identified, of which four were excluded from the analysis
      because of methodological limitations. All studies were non-comparative and only
      nine were prospective. The sample size was generally limited, the mean number of
      patients included being 49 and the mean number of infertile subjects 26. All
      patients were followed for at least 12 months after surgery in 12 studies. The
      combined estimate of pregnancy rates across prospective studies based on a total
      of 138 observed subjects was 57% [95% confidence interval (CI), 48-65%]. Time to
      conception varied from a mean of 8 to 20 months. Survival analysis was used in
      only three studies, with cumulative rates ranging from 57 to 67% at 1 year, and
      63% at 5 years. The overall conception rate among seven prospective studies in
      which only women with otherwise unexplained infertility were recruited was 61%
      (95% CI, 51-70%) compared with 38% (95% CI, 20-59%) in two prospective studies
      that included patients with causes of infertility in addition to myomas (chi2(1)
      = 4.25, P = 0.04; mean difference = 23%, 95% CI, 1-43%; OR = 2.47, 95% CI, 1.03
      5.94). The conception rate ranged from 58 to 65% in the three studies of women
      with only intramural and/or subserous fibroids and were respectively 53 and 70%
      in the two that considered only patients with submucous myomas. Data on
      recurrence after myomectomy were reported in 13 articles, with rates varying from
      4 to 47%. According to the available evidence, slightly less than two-thirds of
      women with uterine leiomyomas and otherwise unexplained infertility conceived
      after myomectomy. However, comparison with expectant management is needed before
      drawing definitive conclusions on the effectiveness of this time-honoured
      conservative surgical procedure.

PMID- 9619541
TI  - Management of chylous ascites following laparoscopic presacral neurectomy.
AB  - Chylous ascites is an extremely rare complication of laparoscopic presacral
      neurectomy (LPSN), and treatment is still controversial. Four patients undergoing
      LPSN for dysmenorrhoea or chronic pelvic pain were complicated with chylous
      ascites. Two were successfully treated with bipolar cauterization and one, after
      the failure of initial treatment by bipolar cauterization, was then effectively
      managed by compression with Gelform and closure of the peritoneum of the
      presacral area by suture through laparoscopy. The fourth patient had persistent
      chyle leakage from the drainage tube after electrocauterization and was finally
      cured by conservative management including removal of the drainage tube and a low
      fat diet for 3 weeks. Chylous ascites has not been reported in laparoscopic
      presacral neurectomy. Management that is quick, effective and subjects the
      patients to the least amount of suffering is still unresolved. Repeated
      laparoscopy can be considered to identify the possibility of injury to lymphatic
      vessels, to relieve abdominal distention due to chyle accumulation, and to apply
      electrocauterization or compression with Gelform and closure of the peritoneum.
      Conservative treatment with a low-fat diet may need a longer time. The use of a
      drainage tube may provide negative pressure allowing a continuous leakage of
      chyle. However, more controlled study is required to identify the most proper and
      effective management.

PMID- 9619542
TI  - Intracytoplasmic sperm injection, results in women older than 39, according to
      age and the number of embryos replaced in selective or non-selective transfers.
AB  - The aim of this study was to assess the results of intracytoplasmic sperm
      injection (ICSI) in a large cohort of women older than 39 according to age and to
      embryo transfer policy. In all, 736 ICSI cycles were analysed retrospectively. In
      576 (78.3%) cycles an embryo transfer was carried out. The embryo transfer was
      defined as non-selective when all the available embryos were transferred, and as
      selective when fewer than the available number of embryos were replaced. A
      statistically significant gradual decrease in the number of embryos available for
      transfer, the number of good or excellent quality embryos available for transfer,
      the pregnancy rates, the clinical pregnancy rates, the implantation rates and the
      viable pregnancy rates was found with advancing age. No viable pregnancies ensued
      in women from 45 years old onwards. There was a statistically significant gradual
      increase in the pregnancy rates, the clinical pregnancy rates, the implantation
      rates and the viable pregnancy rates from non-selective to selective transfers.
      The results were similar in women with five or more embryos available,
      irrespective of the embryo transfer policy. It seems, therefore, that the ovarian
      reserve and the chances for a successful pregnancy decrease gradually with
      advancing age, and it is pointless to treat women from 45 years old onwards. A
      subgroup of patients with better ovarian response and more embryos available for
      transfer have higher chances of conception. Conception and implantation rates
      depend mainly on the quality of the transferred embryos. However, the
      implantation capacity of the embryos is generally lower irrespective of their
      good morphology.

PMID- 9619543
TI  - Correlation between motility of testicular spermatozoa, testicular histology and
      the outcome of intracytoplasmic sperm injection.
AB  - The objective of the present study was to analyse the influence of motility on
      the results of intracytoplasmic sperm injection (ICSI) when testicular
      spermatozoa are used for microinjection and to correlate this with testicular
      histology. A total of 197 ICSI treatment cycles (167 couples) was analysed
      retrospectively in which testicular spermatozoa were used, because of complete
      azoospermia, for microinjection. Fertilization, embryo cleavage, transfer and
      pregnancy rates were evaluated and compared in relation to motility of testicular
      spermatozoa. In 170 cycles, histological diagnoses were compared with findings on
      motility. Injection of motile testicular spermatozoa (in 159 cycles) provided a
      higher normal fertilization rate than did injection of non-motile spermatozoa (in
      14 cycles; 65 versus 45% respectively). Normal spermatogenesis was diagnosed in a
      significantly higher proportion and incomplete maturation arrest in a
      significantly lower proportion in the group of patients in which only motile
      spermatozoa were used for microinjection (65 and 10%), as compared to the group
      where exclusively non-motile spermatozoa were used (36 and 36%). Fertilization
      rate after ICSI was relatively high when non-motile testicular spermatozoa were
      used for microinjection, but use of motile testicular spermatozoa was associated
      with a still higher fertilization rate (except when histology of the testicular
      biopsy showed normal spermatogenesis), and therefore selection of motile
      testicular spermatozoa is always preferable for ICSI. Normal spermatogenesis
      predicts a greater probability, and maturation arrest a lower probability of
      recovering motile testicular spermatozoa.

PMID- 9619544
TI  - Reactive oxygen species: potential cause for DNA fragmentation in human
      spermatozoa.
AB  - The objective of this study was to evaluate the effect of the generation of
      reactive oxygen species (ROS) on the integrity of the DNA of human spermatozoa,
      and to determine if pretreatment with antioxidants can reduce DNA damage. Samples
      were obtained from 47 men undergoing infertility investigation. ROS were
      generated in the samples by the addition of xanthine/xanthine oxidase (X/XO) with
      or without antioxidants. After incubation at timed intervals (0-2 h) with X/XO,
      the percentage of spermatozoa with DNA fragmentation was determined using the
      method of TdT-mediated DNA end-labelling (TUNEL). Time intervals were selected to
      mimic the clinical situation in which spermatozoa are held for a period of time
      after swim-up while the oocytes are prepared for ICSI. A significant increase in
      sperm DNA damage was evident when samples were incubated in the presence of ROS
      for intervals of 1 and 2 h, but not when incubated with ROS for <1 h (P =
      0.0001). The addition of antioxidants significantly decreased the amount of DNA
      damage induced by ROS generation (P < 0.04). ROS can cause an increase in DNA
      fragmentation and pretreatment with antioxidants can reduce DNA damage.

PMID- 9619545
TI  - Fine needle aspiration versus open biopsy for testicular sperm recovery: a
      controlled study in azoospermic patients with normal spermatogenesis.
AB  - This retrospective controlled study aimed at comparing two techniques for
      recovering testicular spermatozoa in azoospermic patients undergoing
      intracytoplasmic sperm injection (ICSI). 102 men suffering from infertility
      because of obstructive azoospermia had ICSI using testicular spermatozoa
      recovered either by open excisional biopsy (n = 51), or by fine needle aspiration
      (FNA) (n = 51). A higher average number of spermatozoa were recovered after open
      biopsy than after FNA, but no significant differences in either fertilization
      rates or cleavage rates were observed after ICSI with spermatozoa retrieved by
      the two techniques. Neither was there any significant difference in ongoing
      pregnancy and implantation rates: in the FNA group, these figures were
      respectively 19.6% per cycle and 7.8% per embryo transferred and in the open
      biopsy group 21.6 and 7.1%. We conclude that ICSI with testicular spermatozoa
      recovered by FNA yields results comparable to those obtained with spermatozoa
      recovered by open biopsy in azoospermic patients with normal spermatogenesis.
      However a prospective study is needed to confirm the present results and to
      assess recovery rates and patient comfort for the two methods.

PMID- 9619546
TI  - Calcium ionophore-induced acrosome reaction correlates with fertilization rates
      in vitro in patients with teratozoospermic semen.
AB  - The aim of this study was to determine the relationship between calcium ionophore
      A23187-induced acrosome reaction (AR) and sperm fertilizing ability. Semen
      samples remaining after preparation for standard IVF were studied in 109 patients
      who had sperm concentrations > or =20 x 10(6)/ml. Ionophore-induced AR was
      performed on motile spermatozoa selected by centrifugation on a Percoll gradient.
      Semen analysis was performed using standard methods. Patients with higher (>50%,
      n = 76) fertilization rates had significantly higher ionophore-induced AR than
      patients with lower (<50%, n = 33) fertilization rates (49 +/- 14 versus 38 +/-
      21%, P < 0.05). When the data from all patients were analysed by logistic
      regression, only the percentage sperm motility in insemination medium and
      ionophore-induced AR were significantly related to fertilization rates. Similar
      results were also obtained when the data from a subgroup of patients with poor
      (<15% normal) sperm morphology were analysed. However, when patients with normal
      sperm morphology > or =15% were analysed separately, only sperm count and the
      percentage of spermatozoa with progressive motility in semen were significantly
      related to fertilization rates. In conclusion, ionophore-induced AR was
      significantly related to fertilization rates in vitro mainly in patients with
      teratozoospermic semen. Tests for ionophore-induced AR may provide additional
      information about sperm fertilizing ability but may not indicate specific defects
      of the physiological AR.

PMID- 9619547
TI  - Correlation between intracellular cAMP content, kinematic parameters and
      hyperactivation of human spermatozoa after incubation with pentoxifylline.
AB  - Various compounds have been used in the attempt to improve sperm motility,
      including pentoxifylline (PF), a methylxanthine derivative. It has been
      postulated that PF, being a phosphodiesterase inhibitor, increases sperm
      kinematic parameters and the number of spermatozoa exhibiting hyperactivated
      motility by raising the intracellular content of cAMP, a molecule involved in the
      generation of sperm energy. However, it has not been clarified whether the
      biological effects of PF on sperm motility correlate with its ability to increase
      intracellular cAMP levels. To examine this relationship, the kinematic
      parameters, hyperactivation, and intracellular cAMP content were evaluated in
      motile spermatozoa, obtained by discontinuous Percoll gradient and swim-up from
      21 normozoospermic semen samples, incubated without and with PF for 0, 1, 2, and
      4 h. PF increased beat cross frequency after 1 and 2 h of incubation, curvilinear
      velocity and lateral head displacement (ALH) after 4 h, and hyperactivation after
      1, 2, and 4 h, and decreased linearity (LIN) after 1 h of incubation. The
      intracellular cAMP content of spermatozoa incubated with PF increased at all time
      points examined. Both intracellular cAMP content and increase in hyperactivation
      in response to PF decreased with the length of incubation. In the absence of PF,
      cAMP content was unchanged and was correlated significantly only with ALH and the
      percentage of spermatozoa with hyperactivated motility. Following incubation with
      PF, cAMP content correlated with hyperactivation and all sperm kinematic
      parameters, with the exception of LIN and straightness. These findings suggest
      that the beneficial effects of PF on sperm kinematic parameters and
      hyperactivation are related to its ability to increase intracellular cAMP
      content.

PMID- 9619548
TI  - Is there a true requirement for follicle stimulating hormone in promoting
      spermatogenesis and fertility in primates?
AB  - Although the role of follicle stimulating hormone (FSH) in regulating ovarian
      function is well accepted, its need in regulating testicular function of the
      adult continues to be debated. Sertoli cells of all mammals have FSH receptors
      and are known to regulate differentiation and transformation of germ cells to
      spermatozoa. However, there appear to be species and age differences in the way
      in which FSH regulates spermatogenesis. An attempt has been made in the current
      paper to examine critically the newer data available in support of and against
      the concept that FSH is required to regulate spermatogenesis and fertility of the
      primate. As there is no evidence to indicate that testicular function in monkeys
      and humans is regulated differently, the information available using the monkey
      as the experimental surrogate model is discussed in some depth. These are
      correlated, wherever feasible, to the newer information emerging from clinical
      studies. It appears from these studies that in the primate (including humans)
      FSH, besides promoting quantitative spermatogenesis leading to production of a
      normal number of spermatozoa, has a critical role in regulating spermiogenesis,
      the process that controls the formation of normal fertilizable mature
      spermatozoa. While the requirement for FSH in promoting fertility in the male
      monkey is reasonably well established, in humans the evidence currently available
      in favour of the concept is still circumstantial and more work needs to be done
      to establish the hypothesis beyond any doubt.

PMID- 9619549
TI  - Inhibin B in seminal plasma: testicular origin and relationship to
      spermatogenesis.
AB  - In men, inhibin B is the circulating isoform involved in the regulation of
      follicle stimulating hormone (FSH) secretion. Within the testis, inhibin B may
      have a role in Sertoli and germ cell interactions, thus secretion into seminal
      plasma may reflect seminiferous tubule function. Using specific immunoassays,
      inhibin B was present in seminal plasma in fertile men (n = 105) and in
      unselected men attending an infertility clinic (n = 174) with a wide range in
      concentration from undetectable (<15 pg/ml) up to 54,100 pg/ml (geometric mean
      280 pg/ml). There was a highly significant correlation between seminal plasma
      inhibin B concentration and sperm concentration (r = 0.46, P < 0.001), but no
      correlation with percentages of spermatozoa with progressive motility or normal
      morphology. Inhibin A and isoforms containing pro and alphaC immunoreactivity
      were not detectable. In post-vasectomy seminal plasma samples (18 of 20) inhibin
      B was undetectable, indicating that the testis is the predominant source. In
      unselected men attending an infertility clinic, inhibin B was undetectable in 17%
      (present in remainder; maximum concentration 26,200 pg/ml; mean 263 pg/ml), with
      a highly significant correlation between seminal plasma inhibin B and sperm
      concentration (r = 0.55, P < 0.0001). In men with oligo/ azoospermia (sperm
      concentration <20 x 10(6)/ml), seminal plasma inhibin B concentrations were lower
      in those with elevated plasma FSH concentrations (mean values 42 and 205 pg/ml, P
      < 0.05). Inhibin alpha and betaB subunits were localized predominantly in Sertoli
      and Leydig cells, using immunohistochemistry. We conclude that inhibin B of
      testicular origin is present in normal human seminal plasma, but with a very wide
      range in concentration, and may reflect the functional state of the seminiferous
      epithelium.

PMID- 9619550
TI  - Inhibin A and B secretion in mouse preantral follicle culture.
AB  - Conditioned media from single mouse ovarian follicles cultured from the early
      preantral stage up to complete maturity were analysed for different
      immunoreactive inhibin forms. The inhibin assays measured (i) alpha-specific
      inhibin, as represented by a mix of 32 and and 57 kDa inhibins, inhibin
      precursors, alpha-subunit and its precursors; (ii) dimeric inhibin A; and (iii)
      dimeric inhibin B. The validity of these assays for the measurement of mouse
      inhibin was established. All forms of inhibin were secreted in culture media from
      the preantral follicle stage onwards. Inhibin B was the most sensitive marker for
      proliferation of early stage follicles, while inhibin A secretion became
      predominant at later stages, when antral-like cavities were formed in granulosa
      cell masses. Supplementation of standard culture medium with recombinant follicle
      stimulating hormone appeared to be the predominant regulator of inhibin
      secretion; addition of recombinant luteinizing hormone throughout the culture
      period did not cause any major shifts in the expression of dimeric inhibin or
      alpha-specific inhibin forms. In the absence of theca cells during isolation and
      culture (as reflected by absence of oestrogen secretion), follicles grew at a
      reduced rate, and produced lower inhibin concentration in conditioned medium.
      These data suggest (i) that monitoring of dimeric inhibins can provide useful
      markers of the growth and differentiation of cultured follicles and (ii) that
      dimeric inhibins A and B are secreted at an earlier stage in vitro than in vivo.

PMID- 9619551
TI  - A monoclonal antibody, HCL-2, raised against human luteal cells reacts with
      apolipoprotein-B and detects the uptake of low density lipoprotein by luteinizing
      granulosa cells.
AB  - A monoclonal antibody, HCL-2, was raised by immunizing mice against human luteal
      cells. HCL-2 reacted with luteal cells and villous trophoblasts. The sodium
      dodecyl sulphate-polyacrylamide gel electrophoresis profile of immunopurified
      antigens from corpus luteum, chorionic villi, and placenta showed the same main
      protein band, the molecular mass of which is >200 kDa. The sequence of a portion
      of the N-terminal region of the antigenic protein purified from placenta was
      identical to that of apolipoprotein-B. The antigen purified from human serum and
      low density lipoprotein (LDL) using HCL-2 showed the same protein band as that
      from corpus luteum. Furthermore, the amino acid sequence (20 amino acids) of the
      protein purified from serum was also identical to that of apolipoprotein-B. Thus,
      we concluded that HCL-2 antigen is apolipoprotein-B. Human luteinizing granulosa
      cells isolated from the patients undergoing in-vitro fertilization treatment were
      cultured in the medium containing lipoprotein-deficient serum with or without
      supplementation of LDL. Using HCL-2, apolipoprotein-B was immunocytochemically
      detected on granulosa cells only in the presence of LDL. These findings showed
      that the uptake of LDL by granulosa cells was detected by immunocytochemical
      staining of apolipoprotein-B, indicating that HCL-2 is useful for analysing
      dynamic utilization of LDL by ovarian cells.

PMID- 9619552
TI  - Stage-specific uptake of apolipoprotein-B in ovarian follicles and corpora lutea
      of the menstrual cycle and early pregnancy.
AB  - A monoclonal antibody (mAb), HCL-2, was raised which reacts with apolipoprotein
      B, and it was shown by immunohistology that HCL-2 can be used to analyse the
      uptake of apolipoprotein-B by steroid-producing cells in vivo. In this study we
      have investigated the dynamic utilization of low density lipoprotein (LDL) in
      human ovary by immunohistological localization of apolipoprotein-B and LDL
      receptors using HCL-2 and anti-LDL receptor mAb. In antral follicles, including
      those of <1 mm in diameter, both apolipoprotein-B and LDL receptors were
      localized to theca interna cells, but not granulosa cells. In pre-ovulatory
      follicles, the LDL receptor was expressed on all granulosa cells. Apolipoprotein
      B was also detected in granulosa cells located at the basal layer, suggesting
      that they utilize LDL through the basal lamina before ovulation. In mid-luteal
      phase, large luteal cells seemed to stain more intensely for apolipoprotein-B
      than did small luteal cells, suggesting that large lutal cells are the main sites
      of LDL utilization. In regressing corpora lutea, the expression of LDL receptor
      was weak, and apolipoprotein-B was rarely detected. In corpora lutea of early
      pregnancy, LDL receptor and apolipoprotein-B were localized to both luteal cells.
      These findings show the precise dynamic changes in LDL uptake by human ovarian
      cells during their differentiation in vivo.

PMID- 9619553
TI  - Cyclic changes of vasculature and vascular phenotypes in normal human ovaries.
AB  - In order to study alterations of angiogenesis and blood vessel regression through
      ovarian cycle in human ovaries we quantitatively examined vascularity in various
      stages in 24 normal human ovaries. Vascular density (VD; vessel numbers/10(-7)
      m2) and endothelial area of each vessel (EA; 10(-12) m2/vessel) were evaluated
      using immunohistochemistry of CD34 and CAS 200 image analysis system. Small-sized
      vessels were sporadically observed in stroma adjacent to primordial or primary
      follicles (6.73 +/- 1.83 for VD and 113.58 +/- 21.80 for EA). Formation of
      capillary network was observed in the theca layer of preantral follicles (PA;
      15.28 +/- 2.77 for VD and 113.58 +/- 21.80 for EA), and higher density of the
      capillary network was detected in non-dominant follicles in follicular phase (ND
      F) and dominant follicles (DF; 29.33 +/- 3.84 for VD and 179.69 +/- 41.25 for
      EA). Dense capillary network was still present in non-dominant follicles in
      luteal phase (ND-L) and atretic follicles (AF; 26.88 +/- 3.36 for VD and 110.88
      +/- 50.53 for EA). After ovulation, developing capillaries were also observed in
      the luteinized granulosa layers in early corpus luteum (21.95 +/- 2.06 for VD and
      167.08 +/- 29.59 for EA). Vessel density markedly increased in mid corpus luteum,
      reached plateau in late corpus luteum (60.85 +/- 5.92 for VD and 70.99 +/- 15.57
      for EA) and remained constant during degenerating corpora lutea. Vascular
      endothelial growth factor was immunohistochemically observed in the theca cells
      in PA, ND-F, DF and ND-L in follicular stages, and functioning corpora lutea.
      Immunoreactivity of intercellular adhesion molecule-1 was detected only in post
      capillary venules in early degenerating corpora lutea. These findings suggest
      that ovarian angiogenesis is a requirement for the early stages of
      folliculogenesis and luteal growth, and also plays an important role in the
      process of follicular atresia and luteal regression.

PMID- 9619554
TI  - Embryos cultured in vitro with multinucleated blastomeres have poor implantation
      potential in human in-vitro fertilization and intracytoplasmic sperm injection.
AB  - The aim of the present study was to investigate pregnancy rates ensuing from
      transfer of embryos with multinucleated blastomeres. In our in-vitro
      fertilization (IVF)/intracytoplasmic sperm injection (ICSI) programme, 1735
      embryo transfers were performed from January 1, 1995 to August 31, 1996. In 136
      of these transfers at least one embryo with one or more multinucleated
      blastomeres was present per transfer (study group). For each of these 136
      transfers, two matched controls with transfer of exclusively mononucleated
      embryos were selected (control group). Matching was carried out according to age,
      method of fertilization (IVF or ICSI), number of transferred embryos and quality
      score of transferred embryos. In the study group, there were eight transfers of
      exclusively multinucleated embryos from which one pregnancy ensued and 128
      transfers in which multinucleated and mononucleated embryos were transferred
      together leading to 23 pregnancies. The overall clinical pregnancy rate per
      transfer was 16.9% in the study group versus 28.7% in the control group (P =
      0.01). The ongoing pregnancy rate per transfer was 13.2% in the study group
      versus 23.2% in the control group (P = 0.03). The implantation rate per
      transferred embryo was 6.0% in the study group versus 11.3% in the control group
      (P = 0.003). This study shows that embryos with one or more multinucleated
      blastomeres have a poorer implantation potential than embryos with mononucleated
      blastomeres. Transfer of embryos with multinucleated blastomeres should hence
      only be considered when insufficient numbers of embryos with only mononucleated
      blastomeres are present.

PMID- 9619555
TI  - Intracellular pH regulation in the human oocyte.
AB  - We have used fluorescence techniques to study the regulation of intracellular pH
      during fertilization and preimplantation embryo development in human oocytes. The
      intracellular pH of human oocytes during maturation and fertilization was always
      7.4, suggesting that these processes do not involve long-term changes in
      intracellular pH. The recovery of intracellular pH of human oocytes and embryos
      after extracellular acid or alkaline shock was investigated. Fresh metaphase II
      oocytes and preimplantation embryos showed similar rates of recovery following
      alkaline shock. However, aged and immature oocytes had a significantly slower
      rate of recovery to physiological pH. Early embryos up to the morula stage were
      unable to recover following acidosis, whereas blastocysts could control both
      acidosis and alkalosis. We assessed the sensitivity of fertilization and early
      development in the human to extracellular pH. Our results show that insemination
      in the human is pH-sensitive, whereas intracytoplasmic injection (ICSI) activated
      oocytes at all pH tested. We suggest that this is due to the pH-sensitivity of
      the sperm-zona pellucida interaction, which is bypassed during the ICSI
      procedure. Further development in human embryos is more sensitive to alkalinity
      than acidity. We discuss these results in terms of the extracellular pH in vivo
      in the female reproductive tract.

PMID- 9619556
TI  - Differential effects of cryopreservation on nuclear or cytoplasmic maturation in
      vitro in immature mouse oocytes from stimulated ovaries.
AB  - The aim of this study was to develop a maturation protocol for immature oocytes
      and assess the protocol with cryopreserved oocytes. Nuclear maturation (mature
      spindle and aligned chromosomes) occurred irrespective of the treatment regime:
      71-89% of oocytes matured in vitro had a normal spindle and chromosomes compared
      with 87% matured in vivo. Fertilization rates were not significantly different
      from those of in-vivo matured oocytes. Of the maturation treatment regimes
      investigated, the initial treatment producing best development to blastocyst
      (cytoplasmic maturation) involved a 2 h incubation in standard maturation medium
      (SMM) containing 7.5 IU follicle stimulating hormone (FSH) followed by 14 h in
      SMM plus 7.5 IU FSH:luteinizing hormone with follicular cells [62% (range 49
      69)]. The addition of 1 ng/ml epidermal growth factor (EGF) in this protocol
      resulted in development [75% (range 71-81)] that was not significantly different
      from in-vivo matured oocytes [82% (range 73-90)]. Exposure of the oocytes to 1.5
      M dimethylsulphoxide (DMSO) did not affect fertilization or development rates.
      Following a slow-cool/thaw freezing regime, 81% (range 74-89) of the oocytes were
      morphologically normal, i.e. had a spherical shape with an intact zona and
      oolemma; they had, however, lost their previously attached cumulus and corona
      cells. Maturation of frozen-thawed oocytes in the presence of EGF gave good
      fertilization rates but poor development rates [80% (range 77-86) and 37% (range
      33-40) respectively]. In conclusion, the best maturation, both nuclear and
      cytoplasmic, occurred in the presence of a combination of gonadotrophins, EGF and
      follicular cells. Oocytes cryopreserved using a slow-cool/thaw regime can be
      matured to produce blastocysts after in-vitro fertilization.

PMID- 9619557
TI  - Formaldehyde in cryoprotectant propanediol and effect on mouse zygotes.
AB  - Cryopreservation of human zygotes and embryos has been routinely performed by in
      vitro fertilization clinics for many years. Karran and Legge (1996) first
      reported that formaldehyde (FA) present in the cryoprotective solutions can have
      a deleterious effect on mouse oocytes. FA is a cytotoxic, carcinogenic and
      mutagenic chemical. The effect of FA on mouse zygotes was investigated. In
      addition, the concentrations of FA in propanediol (PROH) obtained from various
      sources were determined. Pooled 1-cell embryos were dispensed into droplets of
      modified Ham's F10 or human tubal fluid containing various concentrations of FA.
      Since bovine serum albumin (BSA) may minimize toxicity additional trials were
      done as above in the absence of BSA. FA concentration in the standard 1.5 M PROH,
      from different sources in water, was measured in the same assay using a standard
      curve of 0-100 microM FA. FA in a complex medium had a significant deleterious
      effect on embryo development and hatching but only at 1 mM concentration (P <
      0.000001; see Tables I-III). There was no significant effect of FA at 100 microM.
      However, in a simple medium even 50 microM FA decreased embryo hatching. FA was
      present in 1.5 M PROH from different sources (range 1.0-35.3 microM
      concentration). It appears that FA concentrations do not increase with storage
      because FA concentrations were low even after opening and storage for 3 years on
      the shelf. This suggests that FA is a contaminant during the manufacturing
      process and may vary from manufacturer to manufacturer and batch to batch. Until
      further studies are done to confirm the lack of toxicity to embryos during
      cryopreservation (with or without FA scavengers) it may be prudent to screen all
      batches of cryoprotectants for FA as part of quality control.

PMID- 9619558
TI  - Permanent impairment of embryo development by hydrosalpinges.
AB  - Recent reports suggest a deleterious effect of hydrosalpinges on pregnancy
      outcome for in-vitro fertilization (IVF) and improvement following surgical
      treatment. We compared the effect of hydrosalpinx on pregnancy outcome in 286
      patients having 348 IVF cycles and followed the development of untransferred
      embryos for 7 days to determine if hydrosalpinges affect oocyte quality or embryo
      development. The delivery rate per retrieval was significantly lower for patients
      with hydrosalpinx, but was restored by surgical treatment to that of patients
      without hydrosalpinx. However, the implantation rate per embryo transferred and
      normal blastulation of untransferred embryos, which were significantly decreased
      in patients with hydrosalpinx, and growth arrest and degeneration of
      untransferred embryos, which were significantly increased compared to patients
      without hydrosalpinx, were not restored by surgical treatment of hydrosalpinges.
      We conclude that surgical treatment of hydrosalpinges decreases early pregnancy
      loss and improves pregnancy outcome, possibly by diminishing reversible
      deleterious effects exerted on the endometrium. As we have seen in our
      laboratory, hydrosalpinges may have a permanent negative influence on ovarian
      function, follicular development and oocyte quality since implantation of
      transferred embryos and normal blastulation of untransferred embryos remain low,
      and in-vitro growth arrest and degeneration remain high despite surgical
      treatment of hydrosalpinges.

PMID- 9619559
TI  - Monoclonal antibodies to mammalian heat shock proteins impair mouse embryo
      development in vitro.
AB  - Two-cell mouse embryos (B6D2F1) were cultured in the presence or absence of 100
      microg/ml monoclonal antibodies specific for the mammalian 60 kDa (HSP60), 70 kDa
      (HSP70) and 90 kDa (HSP90) heat shock proteins. Embryo development was evaluated
      after 3, 5 and 7 days in culture by determining the number of blastocysts,
      hatched blastocysts and outgrown trophoblasts at the successive time points. At
      day 3, only 29% (22/75) of the embryos cultured with anti-HSP60 antibody
      developed to the blastocyst stage (P < 0.0001) as compared to 67% (31/46) of the
      embryos cultured with anti-HSP70, 72% (43/60) cultured with anti-HSP90, and 79%
      (49/62) in medium plus mouse IgG1. By day 5, hatched embryos were present in 28%
      (13/ 46) of the cultures containing anti-HSP70 (P < 0.0001), as opposed to 57%
      (34/60) containing anti-HSP90 and 73% (45/62) containing IgG1. At day 7, outgrown
      trophoblasts were observed in 9% (4/46) of cultures containing anti-HSP70 (P <
      0.0001), 45% (27/60) containing anti-HSP90 (P < 0.01) and 66% (41/62) cultured in
      medium plus IgG1. Antibodies to different heat shock proteins exerted a
      detrimental effect on mouse embryo development at unique development stages.
      Immune sensitization to heat shock proteins may be a cause of reproductive
      failure.

PMID- 9619560
TI  - Amino acids and vitamins prevent culture-induced metabolic perturbations and
      associated loss of viability of mouse blastocysts.
AB  - Culture of in-vivo-developed mouse blastocysts in a simple culture medium based
      on a balanced salt solution supplemented with carbohydrates for 3 h significantly
      perturbed embryo metabolism. Maximal perturbation occurred after just 6 h of
      culture. Similarly, culture of rat blastocysts in a simple culture medium for 3 h
      also resulted in perturbed metabolism. Cultured mouse and rat blastocysts both
      had an abnormally elevated rate of glycolysis of approximately 100% after culture
      (P < 0.05). Rates of pyruvate oxidation by mouse blastocysts were also
      significantly reduced after culture in a simple medium for 6 h (P < 0.01).
      Furthermore, the developmental competence of mouse blastocysts after transfer was
      significantly reduced by just 6 h of culture in a simple medium (P < 0.05).
      Addition of Eagle's amino acids or vitamins to the culture medium reduced the
      perturbation of both the glycolytic activity and oxidative capacity of cultured
      mouse blastocysts and acted in synergy to further the inhibition. Importantly,
      culture with amino acids and vitamins prevented any loss of viability of mouse
      blastocysts after culture for 6 h. It can be concluded that the mouse blastocyst
      is sensitive to its environment and that culture-induced stress results in the
      loss of normal cellular function, as manifested in this case by an abnormal
      pattern of glucose utilization and loss of viability.

PMID- 9619561
TI  - Detection of reactive oxygen species (ROS) and apoptosis in human fragmented
      embryos.
AB  - In human in-vitro fertilization (IVF)-embryo transfer, the in-vitro culture
      environment differs from in-vivo conditions in that the oxygen concentration is
      higher, and in such conditions the mouse embryos show a higher concentration of
      reactive oxygen species (ROS) in simple culture media. ROS are believed to cause
      damage to cell membranes and DNA fragmentation in somatic cells. This study was
      conducted to ascertain the level of H2O2 concentration within embryos and the
      morphological features of cell damage induced by H2O2. A total of 62 human
      oocytes and embryos (31 fragmented, 15 non-fragmented embryos, 16 unfertilized
      oocytes) was obtained from the IVF-embryo transfer programme. The relative
      intensity of H2O2 concentrations within embryos was measured using 2',7'
      dichlorodihydrofluorescein diacetate by Quanti cell 500 fluorescence imaging and
      DNA fragmentation was observed with transmission electron microscopy and an in
      situ apoptosis detection kit. The H2O2 concentrations were significantly higher
      in fragmented embryos (72.21 +/- 9.62, mean +/- SEM) compared to non-fragmented
      embryos (31.30 +/- 3.50, P < 0.05) and unfertilized oocytes (30.75 +/- 2.67, P <
      0.05). Apoptosis was observed only in fragmented embryos, and was absent in non
      fragmented embryos. Electron microscopic findings confirmed apoptotic bodies and
      cytoplasmic condensation in the fragmented blastomeres. We conclude that there is
      a direct relationship between increased H2O2 concentration and apoptosis, and
      that further studies should be undertaken to confirm these findings.

PMID- 9619562
TI  - The successful use of pronuclear embryo transfers the day following oocyte
      retrieval.
AB  - A retrospective analysis of results from 114 initiated in-vitro fertilization
      cycles utilizing pronuclear embryo transfer is presented. Patients were
      unselected for age or infertility criteria, constituted a continuous series and
      were grouped according to response to stimulation (Group 1, ideal; Group 2,
      suboptimal) or ovarian reserve (Group 3, poor). At 16-18 h post-insemination,
      embryos were scored for alignment of pronuclei and nucleoli and the appearance of
      the cytoplasm, generating an embryo score (ES). Transfers were performed 24-26 h
      post-insemination using two to six embryos with the highest ES. A corrected score
      was calculated (total score/number of embryos; CS). A total of 114 initiated
      cycles resulted in 97 oocyte retrievals with 38 clinical pregnancies (39%; 15%
      implantation). Pregnancy rates were significantly different between the three
      groups; 37 pregnancies in Group 1 (55% clinical pregnancy; 20% implantation),
      none in Group 2 and one in Group 3 (6%; 2% implantation: P < 0.001). The ES of
      transferred embryos correlated with groups. There was a strong correlation
      between CS and implantation and delivery rates. CS >15 resulted in a 28%
      implantation; 65% delivery rate. CS <14 resulted in four pregnancies, one
      delivered. The data show that oocyte quality and pronuclear embryo morphology are
      related to implantation and that pronuclear embryos can be successfully selected
      for embryo transfer.

PMID- 9619563
TI  - Preincubation of human oocytes may improve fertilization and embryo quality after
      intracytoplasmic sperm injection.
AB  - The aim of this study was to examine the relationship between different
      preincubation periods of oocytes and the outcome of intracytoplasmic sperm
      injection (ICSI). We analysed retrospectively 95 ICSI treatment cycles performed
      to alleviate severe male-factor infertility. Oocyte collection was performed
      approximately 36 h after human chorionic gonadotrophin administration. The
      cumulus-corona-oocyte complexes obtained were incubated until the moment of ICSI.
      Fertilization, embryo development and implantation rates were analysed in four
      groups, which were divided according to the time lapse between oocyte retrieval
      and ICSI: group I, < or =3 h (18 cycles); group II, >3-< or =6 h (52 cycles);
      group III, >6-< or =9 h (14 cycles); and group IV, >9-< or =12 h (11 cycles).
      Immediately before ICSI the cumulus and corona cells were removed from the
      oocytes. A total of 723 metaphase II oocytes were injected: 126 from group I, 380
      from group II, 126 from group III and 91 from group IV. The fertilization rates
      obtained were 52.3, 66.8, 65.1 and 69.2% respectively [P < 0.05 (using the chi2
      test) between group I and groups II, III and IV]. Cleavage rates were similar in
      all groups (68.1, 69.7, 79.2 and 79.3% respectively), but the proportion of good
      quality embryos (< or =20% fragmentation) was significantly lower (P < 0.05) in
      group I (24.2%) compared with groups II (39.8%) and IV (39.6%). However, no
      statistically significant differences were observed between the four groups with
      regard to implantation rates (11.7, 13.2, 10.4 and 20.4% respectively). The
      results suggest that a preincubation period between oocyte retrieval and ICSI can
      improve the fertilization rate and embryo quality. This period might be necessary
      for some oocytes to reach full cytoplasmic maturity, leading to a higher
      activation rate upon microinjection.

PMID- 9619564
TI  - Unexpected successful fertilization in vitro of oocytes retrieved 60 hours after
      human chorionic gonadotrophin injection.

PMID- 9619565
TI  - Preparing for preimplantation genetic diagnosis in France.
AB  - Preimplantation genetic diagnosis (PGD) allows the detection of genetic defects
      before implantation, thus circumventing the possible need for abortion. France's
      current legislation allows the practice of PGD under certain circumstances which
      include the prerequisite agreement of the French health authority. Unfortunately,
      to enact the pending 'bioethical law', voted in July 1994, a decree still needs
      to be published. So, for the moment, although we know that PGD should be
      authorized, its practice is currently impossible in France. In order to prepare
      for licensing, we are setting up the relevant technologies, by performing biopsy
      on mouse embryos and fluorescent in-situ hybridization (FISH) experiments on
      human lymphoblast cells. We briefly describe the French legal situation with
      regard to PGD and the work we have performed in this context to obtain the
      licensing to offer PGD to patients. After a period of preparation, 95.9% of
      biopsies were successful and up to 95.4% of the biopsied blastomeres were
      properly spread onto slides. Biopsied and control mouse embryos were reimplanted
      into pseudopregnant females and similar birth rates were obtained (34.4 and 30.9%
      respectively). In these experiments we noticed a birth delay of 12-24 h for the
      biopsied embryos compared with the controls. Furthermore, scanning electron
      microscopy of the biopsied embryos allowed assessment of the hole made by the
      Tyrode's acid. By intercrossing adults derived from biopsied embryos for two
      successive generations, it was shown that the biopsy did not generate defects
      affecting their reproductive ability. FISH experiments were performed using
      specific probes for chromosomes X, Y and 1 on nuclei spread by a conventional
      protocol or a Tween/HCl blastomere spreading protocol; in the latter case, slides
      with 1-5 cells were prepared. A similar percentage of correct X,Y,1,1 signal was
      obtained from all three types of spreading, varying from 85.5 to 89.9%.

PMID- 9619566
TI  - Endometrial vascular and glandular expression of integrin alpha(v)beta3 in women
      with and without endometriosis.
AB  - The integrin alpha(v)beta3 functions in both cell-cell and cell-extracellular
      matrix adhesion, and has reported roles in platelet aggregation, immune function,
      tissue repair, tumour invasion, angiogenesis and uterine receptivity. The aim of
      this study was to use immunohistochemistry to describe the vascular and glandular
      expression of integrin alpha(v)beta3 in formalin fixed, paraffin embedded
      endometrium obtained from women with (n = 29) and without (n = 24) endometriosis.
      The results showed a significant increase in the percentage of vessels expressing
      alpha(v)beta3 in the endometrium of women with endometriosis compared with
      controls (P = 0.0001). This difference was more pronounced in the secretory phase
      (P = 0.001) than the proliferative phase (P = 0.016). There was no correlation
      between vascular alpha(v)beta3 expression and the endothelial cell proliferation
      index (P > 0.05). Vascular sprouts were not observed in any of the 53 endometrial
      tissues obtained from women with or without endometriosis throughout the
      menstrual cycle. Results from semi-quantitative scoring of gland immunostaining
      showed that neither controls (P = 0.3329) nor the endometriosis group (P =
      0.2260) had any significant changes in terms of alpha(v)beta3 expression between
      the different stages of the menstrual cycle. There was also no difference in
      glandular alpha(v)beta3 expression between women with and without endometriosis
      (P = 0.4302). These results provide evidence for increased endometrial
      angiogenesis in women with endometriosis compared with controls, and suggest that
      glandular expression of alpha(v)beta3 is not related to uterine receptivity per
      se.

PMID- 9619567
TI  - Characteristic changes of large granular lymphocytes that strongly express CD56
      in endometrium during the menstrual cycle and early pregnancy.
AB  - Large granular lymphocytes that strongly express CD56 (CD56++ LGL) constitute a
      major population of leukocytes in the secretory endometrium and pregnancy decidua
      and are considered to be involved in reproductive immunity and in maintaining the
      pregnancy. The present study aimed to reveal the relationship between the
      characteristic changes of CD56++ LGL and altered hormonal environment and/or
      trophoblast invasion in the endometrium. Cell surface markers of CD56++ LGL
      obtained from the endometrium during the menstrual cycle and early pregnancy were
      analysed using flow cytometry. The percentages of both CD56++ LGL that express
      activation antigens (CD69, HLA-DR) and those that express lymphocyte function
      associated antigen-1 (LFA-1) (CD11a/CD18) were highest in the proliferative phase
      and decreased gradually throughout the menstrual cycle. Expression of these
      antigens was further suppressed in the late secretory phase, as well as in the
      early stage of pregnancy. However, the percentage of CD56++ LGL that express
      these antigens was significantly higher in spontaneous abortions than in normal
      pregnancies. On the other hand, the percentage of CD56++ LGL that express CD45RA
      was lower during normal pregnancy than during the menstrual cycle. The present
      results suggest that characteristics alterations of CD56++ LGL are regulated by
      altered hormonal environment and by trophoblast invasion.

PMID- 9619568
TI  - Comparison of placental isoferritin levels in maternal serum and coelomic and
      amniotic fluids during first trimester human gestation.
AB  - Placental isoferritin (PLF) is present in serum at high concentrations throughout
      normal gestation. The current study compared PLF concentrations in first
      trimester maternal serum with those of amniotic and coelomic fluids in 25
      healthy, pregnant women. Use of a specific enzyme-linked immunosorbent assay
      indicated concentrations high (22 +/- 3 U/ml) in maternal serum, whereas
      significantly lower values were detected in both coelomic and amniotic fluids (5
      +/- 2 and 3 +/- 2 U/ml, respectively, P < 0.005). It was further demonstrated
      that when pure PLF was added to amniotic and coelomic fluids, the PLF levels
      remained low in each compartment, suggesting that bioproducts produced inside the
      gestational sac may interfere with the PLF immunoassay.

PMID- 9619569
TI  - Effects of luteal phase administration of mifepristone (RU486) and prostaglandin
      analogue or inhibitor on endometrium in the rhesus monkey.
AB  - Early luteal phase administration of a potent anti-progestin like mifepristone
      (RU486) inhibits blastocyst implantation and the establishment of pregnancy
      without marked changes in menstrual cyclicity and ovarian steroid hormone
      profiles; however, the underlying mechanism is not very clear. In the present
      study, a hypothesis that prostaglandins (PG) are involved in the anti-gestatory
      action of luteal phase mifepristone was tested. Endometrial changes in rhesus
      monkeys were examined following luteal phase administration of mifepristone, a
      prostaglandin synthesis inhibitor (diclofenac) and a prostaglandin analogue
      (misoprostol) either alone or in combination. Twenty-five monkeys were randomly
      assigned to six groups: group 1 (n = 4), normal control group; group 2 (n = 4),
      mifepristone (2 mg, daily, s.c.) treated group; group 3 (n = 4), diclofenac (25
      mg, daily, i.m.) treated group; group 4 (n = 4), misoprostol (100 microg, daily,
      oral) treated group; group 5 (n = 5), mifepristone and diclofenac (same dosages
      as for groups 2 and 3) treated group; group 6 (n = 4), mifepristone and
      misoprostol (same dosages as for groups 2 and 4) treated group. All treatments
      were given to monkeys on days 16-18 of mated cycles and endometrial tissue
      samples were collected on day 20. With diclofenac alone (group 3), marginal
      changes were observed in glandular, stromal and vascular compartments, and there
      were few apoptotic bodies in gland cells; partial inhibition and delay in
      implantation was earlier reported. Significantly higher oestrogen receptor
      expression in glandular epithelial cells as compared with all other treatment
      groups was found after treatment with misoprostol alone (group 4) and was
      associated with normal fecundity. The anti-nidatory action of luteal phase
      antiprogestin treatment alone or in combination with diclofenac or misoprostol
      was associated with altered endometrial histometric features characterized by
      glandular apoptosis, regression in secretory functions, decreased oedema,
      extravasation and a higher degree of stromal leukocytic infiltration. In these
      three groups (groups 2, 5 and 6) receptors for oestrogen and progesterone
      receptors were significantly higher in stromal cells, and lower in vascular
      cells, while glandular cells showed significantly higher progesterone receptors
      compared with the control group. The anti-nidatory activity of mifepristone and
      associated endometrial changes could not be accentuated or attenuated with co
      administration of PGE or diclofenac, nor could these be mimicked by these agents
      alone.

PMID- 9619570
TI  - A longitudinal study of maternal serum vascular endothelial growth factor in
      early pregnancy.
AB  - Using a competitive radioimmunoassay to measure total immunoreactive vascular
      endothelial growth factor (VEGF), we describe for the first time longitudinal
      changes in serum VEGF in early pregnancy. The measurements were obtained from 26
      women following the transfer of cryopreserved embryos; 18 singleton and eight
      twin pregnancies were identified by ultrasound at 6 weeks gestation and
      subsequently delivered as live births. Subjects did not have corpora lutea and
      exogenous hormone support was provided for the first 70 days of pregnancy. Serum
      VEGF increased approximately 30 days after embryo transfer and thereafter
      continued to rise in both singleton and twin pregnancies over a period of 20-40
      days after which concentrations remained elevated. The longitudinal profile of
      serum VEGF concentrations was characterized by a logistic curve for singleton and
      twin pregnancies; the profile of VEGF concentrations in the twin pregnancies was
      significantly higher than in the singleton pregnancies (P < 0.0001). Profiles of
      the longitudinal concentrations of serum human chorionic gonadotrophin (HCG),
      oestradiol and progesterone were created by polynomial regression for singleton
      and twin pregnancies. The VEGF profiles were positively correlated with the
      profiles of HCG (r = 0.44, P = 0.02) and oestradiol (r = 0.36, P = 0.07) but not
      progesterone (r = 0.16, P = 0.42). Serum VEGF concentrations in the singleton
      thawed embryo pregnancies were compared with gestation-matched normal singleton
      pregnancies with corpora lutea. Concentrations of VEGF were significantly (P =
      0.004) greater in the pregnancies with corpora lutea although this difference
      became less marked with advancing gestation. In addition to its important role in
      angiogenesis, we speculate that VEGF is involved in mechanisms which control the
      maternal cardiovascular adaptation to pregnancy.

PMID- 9619571
TI  - Effects of methotrexate on trophoblast proliferation and local immune responses.
AB  - Methotrexate is a folic acid analogue that has been used successfully for the
      treatment of ectopic pregnancy and, in conjunction with misoprostol, for medical
      abortions of early intrauterine pregnancies. To administer the most efficacious
      treatment requires knowledge of the mechanism underlying the induction of
      methotrexate-induced abortion. This study was designed to ascertain trophoblast
      integrity, proliferation and differentiation following administration of
      methotrexate. In addition, to determine if methotrexate affects the local uterine
      immune response, we ascertained the numbers and identities of decidual leukocytes
      following treatment. Ten women with undesired intrauterine pregnancies of 42-49
      days gestation were recruited to receive methotrexte 50 mg/m2 i.m. A suction
      aspiration was performed 7 days later. Tissues from gestational age-matched
      elective surgical abortions were used as controls. Additionally, specimens from
      women who received methotrexate and misoprostol for abortion in a clinical trial
      of oral methotrexate in combination with misoprostol, who had a suction abortion
      because of continued embryonic cardiac activity 14 days after the methotrexate,
      were evaluated. Immunoreactivity to proliferating cell nuclear antigen and cyclin
      D3 antibodies was used to demonstrate a marked reduction in the proliferation
      index of cytotrophoblasts from methotrexate-treated abortions. Methotrexate
      treatment failures and non-treated pregnancies had a much higher proliferation
      index. There was no direct destruction of the syncytiotrophoblast, as indicated
      by the continued presence of human placental lactogen and beta-human chorionic
      gonadotrophin proteins. A decrease in the total number of leukocyte cells was
      observed in the decidua of methotrexate-treated samples, with the large granular
      lymphocyte (LGL) cells showing the greatest decline in numbers. Our conclusions
      from this study are that methotrexate acts primarily to derail the normal
      developmental programme of the trophoblast stem cell population, as well as to
      decrease LGL cell numbers in the decidua.

PMID- 9619572
TI  - Maternal and fetal nitric oxide synthesis is decreased in pregnancies with small
      for gestational age infants.
AB  - Our purpose was to evaluate whether maternal and fetal nitric oxide synthesis in
      pregnancies with small for gestational age (SGA) infants are different from those
      in pregnancies with appropriate for gestational age (AGA) infants. Maternal and
      fetal circulating nitrate and nitrite concentrations were compared between 30
      pregnancies with AGA and 10 pregnancies with SGA at birth. End-products of nitric
      oxide synthesis were measured in maternal and cord venous blood samples using a
      fluorometric assay. Umbilical artery blood pH and PO2 were also measured.
      Maternal circulating nitrite and nitrate concentrations (6.91 +/- 1.27 microM) in
      pregnancies with SGA were significantly lower than those (11.69 +/- 1.33 microM)
      in pregnancies with AGA (P = 0.015). Fetal circulating nitrite and nitrate
      concentrations (7.54 +/- 1.09 microM) in pregnancies with SGA were also
      significantly lower than those (11.24 +/- 1.08 microM) in pregnancies with AGA (P
      = 0.024). There were no significant differences in umbilical artery blood pH and
      PO2 between the two groups. These results suggest that maternal and fetal nitric
      oxide synthesis are decreased in pregnancies with SGA infants.

PMID- 9619573
TI  - Pregnancy is associated with hypotrophy of carotid artery endothelial and smooth
      muscle cells.
AB  - It is known that blood flow through the carotid artery is decreased during
      pregnancy, which may be due to a pregnancy-associated increase in the sensitivity
      of this artery to vasoconstrictors. Recent studies have shown that alteration of
      blood flow or pressure could remodel some arteries over a short time frame.
      However, the possibility of remodelling of the carotid artery during pregnancy
      has not yet been examined. Therefore, the aim of the present study was to study
      the morphometrical and stereological characteristics of guinea-pig carotid artery
      during different stages of pregnancy (non-pregnant, early-pregnant, mid-pregnant,
      late-pregnant, n = 8-10 for each group). The cross-sectional area of the
      different layers of the carotid artery and the cross-sectional area of
      endothelial and smooth muscle cells were measured using both light and electron
      microscopy. The values of internal diameter and cross-sectional area of
      adventitia were not significantly different, regardless of the pregnancy status.
      In contrast, external diameter, wall thickness and cross-sectional areas of media
      and intima progressively and significantly decreased during pregnancy. In
      addition, volume/surface density ratio of intima and media also significantly and
      progressively decreased during pregnancy, suggesting hypotrophy of endothelial
      and smooth muscle cells of carotid artery. Indeed, electron microscopy revealed
      that the size, defined as cross-sectional area, of endothelial and smooth muscle
      cells was significantly decreased during different stages of pregnancy. It is
      concluded that during pregnancy there is thinning of the intimal and medial
      layers of guinea-pig carotid artery, which reflect pregnancy-associated
      hypotrophy of carotid artery endothelial and smooth muscle cells.

PMID- 9619574
TI  - HLA-DR typing of women with recurrent late spontaneous abortion and unsuccessful
      cervical cerclage.
AB  - The release of certain cytokines, e.g. tumour necrosis factor (TNF)-alpha, in the
      amniotic fluid has been suggested to be a cause of preterm birth. The
      predisposition to excessive liberation of cytokines from peripheral leukocytes
      has been shown to depend partly on the individual's HLA-DR genotype. The HLA-DR1
      and -DR3 alleles have previously been reported as being associated with a TNF
      alpha high responder status and have also been associated with unexplained
      recurrent spontaneous abortions. In the present study, HLA-DR typing was
      performed in 10 women who had experienced recurrent very early preterm births
      resulting in perinatal death, or late spontaneous abortions under a clinical
      picture resembling that traditionally attributed to cervical incompetence. All
      patients had had at least one mid-trimester miscarriage in spite of the insertion
      of a cervical cerclage. Nine out of 10 (90%) patients had the HLA-DR phenotypes
      DR1 and/or DR3 compared with 37% in the background population (P < 0.005). The
      results suggest that HLA-DR-associated immunological factors might play a part in
      recurrent late spontaneous abortions and extremely preterm births under a
      cervical incompetence-like picture, at least in the subset of cases not treatable
      by cervical cerclage.

PMID- 9619575
TI  - Was the widespread decline in sex ratios at birth caused by reproductive hazards?
AB  - There has been a decline in sex ratio at birth in recent decades in many
      countries. The question arises whether polluting environmental endocrine
      disrupters may have been responsible. It is suggested here that we are not (and
      will not soon become) in a position to know this because: (i) we do not know what
      those sex ratios would have been doing in the absence of such proposed polluters
      and (ii) there are plausible alternative explanations which themselves offer
      little prospect for testing. In short, the population sex ratio at birth seems
      not to be a useful monitor of reproductive hazard unless it were to change at a
      dramatically greater rate than has ever been reported. This is not to deny that
      offspring sex ratios of selected samples of workers have proved useful non
      invasive indicators of reproductive hazard. However, the recent tiny recorded
      secular declines in population sex ratios are distracting attention from the huge
      and unexplained changes in other monitors of reproductive hazard, e.g. the
      widespread decline in dizygotic twinning rates 1960-1980 and the recent probable
      decline in sperm counts.

PMID- 9619576
TI  - Attitudes towards routine human immunodeficiency virus (HIV) screening and
      fertility treatment in HIV positive patients--a UK survey.
AB  - Of 70 fertility units licensed by the Human Fertilisation and Embryology
      Authority in the UK, 58 responded to a questionnaire regarding attitudes towards
      human immunodeficiency virus (HIV) screening and fertility treatment in HIV
      positive patients in November 1995. Of these 58 centres, 23 only performed
      routine screening for HIV for both partners, 24 for hepatitis B and eight for
      hepatitis C. In the event of a positive result in the male, fertility treatment
      would be offered in the form of donor insemination (n = 21), intrauterine
      insemination (IUI) after sperm washing (n = 21), and in-vitro fertilization (IVF)
      (n = 1). If the woman was HIV positive, two centres would offer IUI and three
      centres IVF. Nine centres had already provided treatment for couples in whom the
      male partner was HIV positive and two centres to HIV positive women.

PMID- 9619577
TI  - Serological responses of patients with ectopic pregnancy to epitopes of the
      Chlamydia trachomatis 60 kDa heat shock protein.
AB  - Clinical and histopathological correlations of immunoreactivity to Chlamydia
      trachomatis and to epitopes of the C. trachomatis 60 kDa heat shock protein
      (hsp60) among women with ectopic pregnancy were evaluated in a case-control
      study. Serological responses to 13 synthetic peptides corresponding to major
      epitopes of the chlamydial hsp60 were determined in 67 women treated for ectopic
      pregnancy and 45 women with uncomplicated pregnancy in utero. Plasma cell
      salpingitis was detected in 29 (43.3%) of the ectopic patients. Its presence
      correlated with antibodies to two hsp60 epitopes, encompassing amino acids 260
      271 and 411-422 (P = 0.02). Antibodies to these two epitopes, along with five
      other epitopes, also correlated with peritubal adhesion formation in ectopic
      pregnant patients (P < 0.01). Antibodies to epitopes 260-271 and 188-199 also
      correlated with a history of pelvic inflammatory disease (PID; P = 0.05).
      Patients with ectopic pregnancy were also more likely than their intrauterine
      pregnant controls to have present anti-chlamydial immunoglobulin G (P < 0.005).
      Women positive for both C. trachomatis and hsp60 epitope antibodies had an
      increased prevalence over controls of salpingitis, pelvic adhesions or history of
      PID (P < 0.05). In contrast, patients who were positive for only C. trachomatis
      antibodies or only hsp60 epitope antibodies did not differ from antibody-negative
      patients in each of these categories.

PMID- 9619578
TI  - How to use Chlamydia antibody testing in subfertility patients.
AB  - Screening for tubal factor subfertility by means of Chlamydia antibody testing
      (CAT) was introduced into the initial work-up of subfertile couples several years
      ago. The results reported, however, are heterogeneous, and no uniformity exists
      in cut-off levels of titres, or in definitions of tubal factor subfertility. We
      performed a prospective cohort study to evaluate the implications of varying the
      definitions of tubal pathology and of modifying the cut-off levels on the
      clinical impact of CAT in predicting tubal factor subfertility. In 227
      consecutive patients who attended our fertility clinic, the Chlamydia IgG
      antibody titre was determined and related to tuboperitoneal abnormalities at
      laparoscopy as a reference standard. According to received operating
      characteristic (ROC) curve analysis, a titre of 16 is the optimum cut-off level.
      Increasing the cut-off level improves specificity and positive likelihood ratio
      (LR+), at the expense of sensitivity and negative LR (LR-). Changing the
      definition of tubal factor subfertility from unspecified tuboperitoneal
      abnormalities into extensive adhesions and/or bilateral distal tubal occlusion
      improves LR+, LR- and kappa significantly. We conclude that CAT is more accurate
      in predicting severe distal tubal pathology than unspecified tuboperitoneal
      abnormalities. Although from a statistical point of view a titre of 16 is the
      optimum cut-off level, from a clinical point of view 32 or 64 may be preferable,
      depending on the aim of screening and the inception cohort.

PMID- 9619579
TI  - Adjusting to life when assisted conception fails.
AB  - According to our basic (psychosomatic) tenet, every somatic problem has its
      emotional side; therefore, medical treatment and counselling are not separate but
      are interlinked and equally important. First interviews and interviews after
      failed assisted reproductive technology (ART) are held together in four person
      settings; the couple with two counsellors. The sessions last for approximately 1
      h. The aim is to help patients escape the agonizing and distressing state in
      which they are kept by their foci (psychogenic aspects causing distress). Stress
      and iatrogenic factors are discussed and when patients are able to re-experience
      their suffering, many possible psychological effects on infertility and/or
      treatment failure are explored. If the patients consciously perceive these
      mechanisms of action, they will turn to their basic emotional needs and
      perspectives; approximately 30% of them will conceive later while approximately
      20% opt for adoption. However, half of the patients take no positive action,
      neither giving up nor continuing with activities for a child. Nor do they seek
      counselling. The analysis of many of their reports argues in favour of an
      adaptive model for coping with reproductive failure.

PMID- 9619580
TI  - Statutory information for the children born of oocyte donation in the UK: what
      will they be told in 2008?
AB  - In the UK, non-identifying information on the donor is recorded by statute in
      assisted reproduction with gamete donation. This may be made available eventually
      to the resulting children. Prospective parents are counselled about openness, and
      often wish to know what may be available if the child has access to this
      information. We analysed forms from the Human Fertilisation and Embryology
      Authority completed by all donors at the Lister in-vitro fertilization unit. We
      found that 94% of oocyte donors did not respond to the last question asking for a
      brief description of themselves, leaving only profession and interests as
      information to be given in the future. There was a significant difference between
      the known and anonymous responders. This has important implications for the
      future parents who want to tell their child of his/her origins.

PMID- 9619581
TI  - Testicular sperm aspiration (TESA): the appropriate technique.

PMID- 9619582
TI  - Mode of delivery after uterine metroplasty.

PMID- 9619584
TI  - Accuracy of secondary structure and solvent accessibility predictions for a
      clostridial neurotoxin C-fragment.
AB  - Earlier studies used Rost and Sander's artificial neural network [(1993a), J.
      Mol. Biol. 232, 584-599] to predict the secondary structures [Lebeda and Olson
      (1994), Proteins 20, 293-300] and residue solvent accessibilities [Lebeda and
      Olson (1997), J. Protein Chem. 16, 607-618] of the clostridial neurotoxins.
      Because the X-ray crystal structure of the 50-kDa C-terminal half of the heavy
      chain of tetanus toxin was recently determined, this report evaluates the
      accuracy of these network-derived predictions. For this predominantly beta-strand
      containing fragment, predictions, on a per-residue basis, for both secondary
      structure and solvent accessibility were about 70% accurate. A more flexible and
      realistic analysis based on overlapping segments yielded accuracies of over 80%
      for the three-state secondary structure and for the two-state accessibility
      predictions. Because the accuracies of these predictions are comparable to those
      made by Rost and Sander using a dataset of 126 nonhomologous globular proteins,
      our predictions provide a quantitative foundation for gauging the results when
      building by homology the structures of related proteins.

PMID- 9619583
TI  - Tubulin stability and decay: mediation by two distinct classes of IKP104-binding
      sites.
AB  - IKP104, a novel antimitotic drug, has two classes of binding sites on bovine
      brain tubulin with different affinities. IKP104, by itself, enhances the decay of
      tubulin, but in the presence of colchicine or podophyllotoxin, it stabilizes
      tubulin instead of opening up the hydrophobic areas [Luduena et al. (1995),
      Biochemistry 34, 15751-15759]. Here, we have dissected these two apparently
      contradictory effects of IKP104 by cleaving the C-terminal ends of both alpha and
      beta subunits of tubulin with subtilisin. We have found that the selective
      removal of the C-terminal ends from both the alpha and beta subunits of alphabeta
      tubulin lowers the sulfhydryl titer by approximately 1.5 mol/mol of dimer.
      Interestingly, IKP104 does not increase either the sulfhydryl titer or the
      exposure of hydrophobic areas of this subtilisin-treated tubulin
      (alpha(s)beta(s)). Moreover, IKP104 lowers the sulfhydryl titer of
      alpha(s)beta(s) tubulin approximately by 1 mol/mol and appears to inhibit
      completely the time-dependent decay of alpha(s)beta(s) tubulin. The cleavage at
      the C-terminal ends of both alpha and beta modulates the effect of IKP104 on the
      beta subunit, but not on the alpha subunit. Fluorometric binding data analysis
      suggests that IKP104 binds to the alpha(s)beta(s) tubulin only at the high
      affinity site; the low-affinity site(s) disappear almost completely. The
      sulfhydryl titer data for alpha and beta and the fluorometric data therefore
      suggest that the interaction of IKP104 at the high-affinity site on tubulin is
      not regulated by the C-terminal domains of alpha and beta and the effect of the
      high-affinity site is restricted largely to the alpha subunit, while the low
      affinity-site binding is modulated by the C-terminal domain of beta. It also
      appears that the stabilization and the acceleration of the decay of tubulin are
      mediated by distinct interactions of IKP104 with its high- and low-affinity sites
      on tubulin, respectively.

PMID- 9619585
TI  - Analysis of the global architecture of hemoglobin A2 by heme binding studies and
      molecular modeling.
AB  - The kinetics of CNProto- and CNDeutero-hemin binding to apohemoglobin A2 was
      investigated in a stopped-flow device in 0.05 M potassium phosphate buffer, pH 7,
      at 10 degrees C. The overall kinetic profile exhibited multiple phases: Phases I
      IV corresponding with heme insertion (8.5-13 x 10(7) M(-1) s(-1)), local
      structural rearrangement (0.21-0.23 s(-1)), global alphadelta structural event
      (0.071-0.098 s(-1)), and formation of the Fe-His bond (0.009-0.012 s(-1)),
      respectively. Kinetic differences observed between apohemoglobin A2 and
      apohemoglobin A (previously studied) prompted an analysis of the structures of
      beta and delta chains through molecular modeling. This revealed a structural
      repositioning of the residues not only at, but also distant from the site of the
      amino acid substitutions, specifically those involved in the heme contact and
      subunit interface. A significant global change was observed in the structure of
      the exon-coded 3 region and provided additional evidence for the designation of
      this as the subunit assembly domain.

PMID- 9619586
TI  - Differential tyrosine phosphorylation/activation of oncogenic proline-directed
      protein kinase F(A)/GSK-3alpha in well and poorly differentiated human prostate
      carcinoma cells.
AB  - Computer analysis of protein phosphorylation site sequences revealed that
      transcriptional factors and viral oncoproteins are prime targets for regulation
      of proline-directed protein phosphorylation, suggesting an association of the
      proline-directed protein kinase (PDPK) family with neoplastic transformation and
      tumorigenesis. In this report, an immunoprecipitate activity assay of proline
      directed protein kinase F(A)/glycogen synthase kinase-3alpha (PDPK F(A)/GSK
      3alpha) has been optimized to demonstrate significantly increased (p < 0.01)
      activity in poorly differentiated human prostate carcinoma PC-3 cells (55.5+/-3.8
      units/mg) when compared to well-differentiated LNCaP cells (28.1+/-2.3 units/mg).
      Immunoblotting analysis revealed that increased activity of this PDPK in PC-3
      cells is due not to overexpression of the protein, but to enhanced tyrosine
      phosphorylation of the kinase. When treated with genistein (a protein tyrosine
      kinase PTK inhibitor), the enhanced tyrosine phosphorylation/activation of the
      kinase in PC-3 cells can be blocked. Conversely, when treated with vanadate (a
      protein tyrosine phosphatase PTP inhibitor), the phosphotyrosine content of PDPK
      F(A)/GSK-3alpha in LNCaP cells can be promoted to the level of PC-3 cells. In
      sharp contrast, the PTK inhibitor has little effect on the tyrosine
      phosphorylation level of the kinase in LNCaP cells, whereas the PTP inhibitor has
      little effect on the tyrosine phosphorylation level of the kinase in PC-3 cells.
      Taken together, the results provide initial evidence that the tyrosine
      phosphorylation/activation levels of this oncogenic PDPK can be differentially
      regulated in well- and poorly differentiated prostate carcinoma cells.

PMID- 9619587
TI  - CNBr/formic acid reactions of methionine- and trifluoromethionine-containing
      lambda lysozyme: probing chemical and positional reactivity and formylation side
      reactions by mass spectrometry.
AB  - The cyanogen bromide (CNBr)/formic acid cleavage reactions of wild-type and
      trifluoromethionine (TFM)-containing recombinant lambda lysozyme were studied
      utilizing ESI and MALDI mass spectrometry. Detailed analysis of the mass spectra
      of reverse-phase HPLC-purified cleavage fragments produced from treatment of the
      wild-type and labeled proteins with CNBr indicated cleavage solely of methionyl
      peptide bonds with no observation of cleavage at TFM. N-Acetyl-TFM was also found
      to be resistant to reaction with CNBr, in contrast to N-acetyl-methionine. The
      analysis also indicated differential reactivity among the three methionine
      positions in the wild-type enzyme. Additionally, formylation of intact enzyme as
      well as peptide fragments were observed and characterized and indicated that
      serine, threonine, as well as C-terminal homoserine side chains are partially
      formylated under standard cleavage protocols.

PMID- 9619588
TI  - Isolation and characterization of two forms of an acidic bromelain stem
      proteinase.
AB  - Two forms of an acidic bromelain proteinase isolated from crude bromelain, an
      extract from pineapple stem, were found by a two-step FPLC purification
      procedure. The basic main components were removed by cation exchange
      chromatography and the breakthrough fraction was further resolved by anion
      exchange chromatography into 15 protein fractions, only two of which, called
      SBA/a and SBA/b, were proteolytically active. These components were characterized
      by electrospray mass spectroscopy (ESMS), isoelectric focusing, N-terminal amino
      acid sequence analysis, monosaccharide analysis, and enzymatic parameters. The
      molecular masses of SBA/a and SBA/b were determined by ESMS to be 23,550 and
      23,560, respectively. The isoelectric points (pI) of the two bands of SBA/a were
      4.8 and 4.9; SBA/b focused as a single band at pI = 4.8. Partial N-terminal amino
      acid sequences (11 residues) were identical to SBA/a and SBA/b and identical with
      those of stem bromelain, the basic main proteinase of the pineapple stem, and
      fruit bromelain, the acidic main proteinase of the pineapple fruit. Both
      components are highly glycosylated; hydrolysis of SBA/a yielded about twofold
      more monosaccharide per protein than SBA/b. The comparison of the catalytic
      properties of SBA/a with those of SBA/b revealed no relevant differences in the
      hydrolysis of three peptidyl-NH-Mec substrates and in the inhibition profiles
      using chicken cystatin and E-64, indicating that these components can be
      considered as two forms of a single enzyme. Both forms are scarcely inhibited by
      chicken cystatin and slowly inactivated by E-64, hence are nontypical cysteine
      proteinases of the papain superfamily.

PMID- 9619589
TI  - Prediction of beta-turns.
AB  - Kohonen's self-organization model, a neural network model, is applied to predict
      the beta-turns in proteins. There are 455 beta-turn tetrapeptides and 3807 non
      beta-turn tetrapeptides in the training database. The rates of correct prediction
      for the 110 beta-turn tetrapeptides and 30,229 non-beta-turn tetrapeptides in the
      testing database are 81.8% and 90.7%, respectively. The high quality of
      prediction of neural network model implies that the residue-coupled effect along
      a polypeptide chain is important for the formation of reversal turns, such as
      beta-turns, during the process of protein folding.

PMID- 9619590
TI  - Molecular dynamic simulation of chaperonin-mediated protein folding.
AB  - We use molecular dynamics methods to simulate chaperonin-mediated refolding of
      barnase. A "chaperonin" term is added to the force field in order to simulate the
      hydrophobic environment in the central cavity of the chaperonins. Two aspects of
      our simulation results are consistent with experiments: (1) The hydrophobic
      environment of the central cavity of the chaperonin is an advantageous condition
      for the refolding of the misfolded intermediates. (2) One cycle of binding and
      release is not enough for the successful folding. Chaperonin-assisted protein
      folding maybe a procedure of multiple cycles of binding and release from the
      chaperonin.

PMID- 9619591
TI  - The amino acid sequence of bothropstoxin-II, an Asp-49 myotoxin from Bothrops
      jararacussu (Jararacucu) venom with low phospholipase A2 activity.
AB  - The complete amino acid sequence of bothropstoxin-II (BthTX-II), a myotoxin
      isolated from Bothrops jararacussu snake venom, is reported. The results show
      that BthTX-II is an Asp-49 phospholipase A2 (PLA2)-like protein composed of a
      single polypeptide chain of 120 amino acid residues (Mr = 13,976), containing one
      methionine and 14 half-cystines. Despite a high degree of homology with other
      PLA2's and the presence of the strategic residues known to compose the Ca2+
      binding loop, namely Tyr-28, Gly-30, Gly-32, and especially Asp-49, besides His
      48, Tyr-52, and Asp-99, all of them directly or indirectly involved in catalysis,
      BthTX-II revealed a very low PLA2 activity when assayed on egg yolk
      phosphatidylcholine. We attribute this low catalytic activity to the existence of
      extra mutations, e.g., Trp-5 for Phe-5, which points to the need of considering
      other strategic positions, since only Lys-49 PLA2's have been considered to be
      devoid of this enzymatic activity.

PMID- 9619592
TI  - Distribution of human herpesvirus 8 DNA in tumorous and nontumorous tissue of
      patients with acquired immunodeficiency syndrome with and without Kaposi's
      sarcoma.
AB  - Human herpesvirus 8 (HHV-8) DNA is present in virtually all Kaposi's sarcomas
      (KSs). Conflicting results, however, exist with respect to the presence of HHV-8
      in nontumorous tissue samples. To define the specificity and predictive value of
      HHV-8 DNA detection in KS, we analyzed autopsy-derived tissue samples from
      patients with acquired immunodeficiency syndrome (AIDS) with and without KS for
      the presence of HHV-8 DNA, using single-step and nested polymerase chain
      reaction. Semiquantitative analysis of HHV-8 DNA was performed by endpoint
      dilution assays. HHV-8 DNA was detected in 41 (100%) tumor tissue samples of KSs.
      According to nested polymerase chain reaction results, HHV-8 DNA was also present
      in 16 (32%) of 50 nontumorous specimens of patients with AIDS patients with KS
      and in 3 (2.7%) of 113 specimens of patients with AIDS without KS; it was absent
      in 26 autopsy tissues and 15 transurethral resected prostatic specimens of
      patients without AIDS. By use of a second, unrelated primer set, the presence of
      HHV-8 DNA was confirmed in 12 (63.2%) of 19 nontumorous samples and detected in
      another 6 (17.7%) of 34 samples tested. Significantly higher titers of HHV-8 DNA
      were found in tumorous than in nontumorous tissues samples (1.9 x 10(4) vs. 1.2 x
      10(2); P < .05). Specificity and positive predictive values for the diagnosis of
      KS by detecting HHV-8 DNA in a given tissue sample were 56 and 65.1% in patients
      with manifest KS and 97.4 and 100% in patients without previously known KS. An
      increased specificity and a positive predictive value were observed when the
      presence of KS anywhere in a given patient was considered (92.9 and 77.8%,
      respectively). In conclusion, the detection of HHV-8 DNA is a sensitive test for
      the diagnosis of KS. Its specificity, however, might be lower because HHV-8 can
      be detected in histologically unaffected tissue of patients with KS.

PMID- 9619593
TI  - Comparative genomic hybridization of low-grade central osteosarcoma.
AB  - Very little is known concerning the cytogenetic and molecular genetic changes of
      low-grade central osteosarcoma, a rare form of osteosarcoma. In the present
      study, we used comparative genomic hybridization (CGH) to screen for DNA sequence
      copy number aberrations in 10 samples from 6 patients: 7 typical low-grade
      central osteosarcomas, one low-grade (Grade II) central osteosarcoma, and two
      high-grade (III and IV) local recurrences of a low-grade central osteosarcoma
      Nine samples had aberrations. Six typical low-grade central osteosarcoma samples
      had a single DNA sequence copy number change per tumor. Three samples from more
      advanced tumors (a Grade II low-grade central osteosarcoma and local recurrences
      of Grade III and IV) had a mean of five changes per tumor. Recurrent changes
      affected these minimal common regions: +12q13-q14 (three tumors), +12p (two
      tumors), and +6p21.1-p21.3 (two tumors). Nine samples were analyzed for CDK4 and
      MDM2 expression and SAS amplification. One sample with a gain of chromosome 12
      had a very strong expression of MDM2, strong expression of CDK4, and
      amplification of SAS. One sample with a gain of 12q13-q14 had strong expression
      of CDK4 and MDM2. Strong expression of CDK4 was found in two additional tumors;
      one had a gain of 12q13-q21, and the other had no changes in chromosome 12 by
      CGH. No alterations were detected in the CDK4, MDM2, and SAS panel in three other
      samples with no changes in chromosome 12 by CGH. In conclusion, the low number of
      DNA sequence copy number alterations reflects the relatively low malignancy of
      low-grade central osteosarcoma. This simplicity differs from the complex
      aberrations seen in conventional high-grade osteosarcomas.

PMID- 9619594
TI  - Frozen section biopsy assessment for the presence of polymorphonuclear leukocytes
      in patients undergoing revision of arthroplasties.
AB  - Despite progress in techniques, early or late deep infection develops in 1 to 5%
      of patients with prosthetic joint replacements. We report a retrospective review
      of 64 original frozen sections (FSs) compared with permanent sections, the
      preoperative clinical and intraoperative findings, and the subsequent culture
      results. A histologic section, frozen or permanent, was considered positive for
      infection if there were more than five polymorphonuclear leukocytes (PMNs) per
      high power field, excluding surface fibrin and inflammatory exudate, in at least
      five separate microscopic fields. The sensitivity of an FS as a diagnostic test
      to detect prosthetic infection when present was 43%. The specificity of an FS to
      correctly identify the absence of infection was 97%. These data support the
      conclusion that the FS is reasonably specific but not a sensitive diagnostic
      modality. If the preoperative evaluation is completely negative and the FS does
      not reveal PMNs, the reimplantation can be performed with minimal concern
      regarding the possibility of infection. If the preoperative and intraoperative
      evaluations are completely negative but PMNs are observed in the FS, then the
      surgeon should consider proceeding with caution; the decision to proceed with
      reimplantation might be delayed, depending on the surgeon's clinical assessment.

PMID- 9619595
TI  - Pulmonary mycotoxicosis: a clinicopathologic study of three cases.
AB  - Pulmonary mycotoxicosis (PM), also termed organic dust toxic syndrome or silo
      unloader's syndrome, is an acute illness resulting from massive inhalation of
      microbial toxins in organic dusts. It has not been well described histologically.
      Three cases of PM are presented in this report. Open lung biopsies were examined
      in each case. All of the patients were farmers with no prior lung disease. One
      had burning in his eyes, throat, and chest after exposure to moldy silage;
      chills, fever, dry cough, malaise, and weakness developed within 24 hours. Two
      patients presented with fever, progressive dyspnea, cough, and fatigue within 24
      hours of emptying a corncrib, cleaning a chicken coop, and baling hay. Bilateral
      alveolar and interstitial infiltrates on chest roentgenograms and leukocytosis
      with neutrophilia were observed in all of the three patients. Two patients became
      hypoxemic and required mechanical ventilation. Histologic examination showed
      acute and organizing diffuse alveolar damage in two biopsy specimens and an acute
      bronchopneumonia in the third. One specimen had 1- to 10-microm ovoid organisms
      demonstrable with methenamine silver stains; cultures grew Fusarium and
      Penicillium species. The other two biopsy specimens had negative tissue cultures
      and special stains for organisms, although Penicillium species were grown from a
      preoperative bronchoalveolar lavage in one case. The two patients on mechanical
      ventilation recovered completely with high-dose steroids. The third patient
      recovered without steroids. No patient had residual functional deficits or chest
      radiographic abnormalities. PM can be distinguished from allergic and infectious
      diseases common in individuals exposed to large amounts of organic dust by its
      clinicopathologic features.

PMID- 9619596
TI  - Expression of facilitative glucose transporter isoforms in lung carcinomas: its
      relation to histologic type, differentiation grade, and tumor stage.
AB  - Expression of facilitative glucose transporter (Glut) isoforms was studied
      immunohistochemically in lung carcinomas. Glut-1 was expressed in 45 (74%) of 61
      lung carcinomas, including 19 (100%) of 19 squamous cell carcinomas. No Glut-1
      staining was seen in normal lung epithelium surrounding the tumors. In squamous
      cell carcinomas and small cell carcinomas, Glut-1 immunostaining was stronger in
      the central area of tumor cell nests corresponding to the hypoperfused region.
      Focal staining was seen in 14 (58%) of 24 adenocarcinomas, and positive staining
      was correlated to lesser differentiation, larger tumor size, and positive lymph
      node metastasis. Glut-2 was detected in normal airway epithelium, but no positive
      staining was seen in lung carcinomas. Glut-3 and Glut-4 were not positively
      stained in normal lung epithelia, but a few lung carcinoma samples showed
      positive reaction (9 of 61 in Glut-3; 4 of 61 in Glut-4). Glut-4 immunoexpression
      was seen in regenerating alveolar and bronchiolar epithelia around and in cancer
      tissues. Glut-5 expression was not detected in normal and tumor tissues. Reverse
      transcriptase-polymerase chain reaction for Glut-1, Glut-3, and Glut-4 confirmed
      the expression revealed by immunohistochemical analysis. Overexpression of Glut
      could enhance uptake of glucose into lung carcinoma cells, and the increased
      glucose influx could be involved in cell biologic activities.

PMID- 9619597
TI  - Pancreatic B-cell proliferation in persistent hyperinsulinemic hypoglycemia of
      infancy: an immunohistochemical study of 18 cases.
AB  - Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is characterized by
      severe hypoglycemia related to inappropriate insulin secretion. Morphologically,
      a tumoral and a nontumoral form are recognized. The tumoral form can be
      subdivided into adenomatous hyperplasia (in infants) and adenoma (in children).
      On the other hand, nesidioblastosis, considered until recently as a persistent B
      cell replication, has repeatedly been proposed as the condition responsible for
      the nontumoral form of PHHI. We studied the proliferation rate of B cells in 18
      patients affected by PHHI (7 nontumoral and 11 tumoral cases, including 4
      adenomas and 7 adenomatous hyperplasias) and in 18 age-matched controls, using a
      double immunohistochemical technique detecting Ki-67, a nuclear endogenous
      antigen only present during cell proliferation, and insulin as pancreatic B-cell
      markers. Our results clearly show that "nesidioblastosis" is not related to an
      abnormal B-cell proliferation, because the B-cell labeling index (LI), reported
      as the mean plus or minus the standard error of the mean, is not statistically
      different between nontumoral PHHI (29.4 +/- 7.4) and age-matched controls (19.6
      +/- 5.3). Furthermore, the Ki-67 positivity was not more prominent in small
      clusters of B cells in nesidioblastosis than in large islets. In tumoral PHHI,
      the LI was significantly higher in cases of focal adenomatous hyperplasia (77.6
      +/- 10.9) than in either age-matched controls (19.9 +/- 6.9; P < .005) or in
      adenomas (27.9 +/- 13.7; P < .025); the values of this last group did not differ
      from those of age-matched controls (18.5 +/- 8.5). These data definitely
      demonstrate that nesidioblastosis does not correspond to an abnormal B-cell
      proliferation and that the focal forms of PHHI must be subclassified.

PMID- 9619598
TI  - The immunohistochemical marker Ki-S2: cell cycle kinetics and tissue distribution
      of a novel proliferation-specific antigen.
AB  - The monoclonal antibody Ki-S2 binds to a recently characterized proliferation
      specific protein, p100. To assess its distribution pattern under physiologic and
      pathologic conditions, we performed immunohistochemical analyses on an exhaustive
      spectrum of normal tissues, 624 miscellaneous solid cancers, and 95 hematologic
      malignancies, and compared the results with Ki-67 immunostaining on consecutive
      sections. In addition, Ki-S2 expression was related to the DNA content by dual
      parameter flow cytometric analysis in parallel with Ki-67 labeling using a human
      cancer cell line. Immunoreactivity was enhanced at the G1/S transition and
      persisted through G2 and M phase. After adequate antigen retrieval, the antibody
      was found to yield identical results on fresh and formalin-fixed, paraffin
      embedded material. The antibody specifically labeled actively proliferating
      cells, which constitute a subset of the population recognized by Ki-67. In normal
      human tissues, Ki-S2 immunolabeling hardly ever exceeded 40% of the Ki-67+ cell
      fraction. Immunoreactive scores of the two antibodies exhibited a linear
      correlation, but statistically significant differences in the ratio of Ki-S2
      positive to Ki-67-positive cells were nevertheless observed between different
      tissue types. In contrast, the ratio of Ki-S2 and Ki-67 immunoreactive scores
      varied widely in neoplastic cells and tissues, occasionally attaining a ratio of
      almost 1:1. This suggests that loss of growth regulatory mechanisms in malignant
      cells might result in an extreme reduction of the G1 phase fraction and thus in a
      significantly shorter doubling time. Therefore, antibody Ki-S2 is likely to allow
      a more precise evaluation of the cell fraction that will complete a division
      cycle and a more confident appraisal of the malignancy potential of a neoplastic
      process.

PMID- 9619599
TI  - Immunohistochemical detection of E2F-1 in non-Hodgkin's lymphomas: a survey of
      124 cases.
AB  - E2F-1 is a transcription factor that mediates cell cycle progression from the G1
      to S phase and is normally regulated by a group of proteins, including cyclin D1.
      Although deregulation of E2F-1 is implicated in neoplastic transformation, in
      situ examination of this protein has not been performed to date. Using an
      immunohistochemical technique applied to routinely fixed, paraffin-embedded
      tissue sections, we evaluated E2F-1 expression in reactive lymphoid tissues and
      in 124 cases of non-Hodgkin's lymphoma (NHL) of various types. In reactive
      lymphoid tissues, E2F-1 was expressed predominantly by large noncleaved cells in
      germinal centers and by a small subset of cortical thymocytes. Mantle zones and
      splenic marginal zones were negative. Among the NHLs, four types had a relatively
      high percentage (> 20%) of E2F-1-positive cells: mantle cell lymphoma (19 of 19),
      lymphoblastic lymphoma (5 of 5), small noncleaved cell lymphoma (4 of 6), and
      hepatosplenic gammadelta T-cell lymphoma (3 of 3). The consistent detection of
      many E2F-1-positive cells in mantle cell lymphoma is in contrast to other small B
      cell NHLs (n = 29), which had relatively few (< 10%) E2F-1-positive cells. This
      finding suggests that immunohistochemical staining for E2F-1 as a supplement to
      the existing markers, such as cyclin D1, might be useful in the differential
      diagnosis of NHLs composed of small B cells.

PMID- 9619600
TI  - Correlation of bcl-2, p53, and MIB-1 expression with ependymoma grade and
      subtype.
AB  - In this study, we report our results on the proliferative activity of ependymomas
      as determined by MIB-1 (also known as Ki-67) immunohistochemical analysis, and we
      compare our results with those obtained by immunolabeling with monoclonal
      antibodies to p53 and bcl-2 proteins to assess whether expression correlated with
      ependymoma subtype or tumor grade. The study included 4 myxopapillary ependymomas
      (Grade I of the World Health Organization [WHO] scale), 10 subependymomas (WHO
      Grade I), 17 ependymomas (WHO Grade II), 2 papillary ependymomas (WHO grade II),
      and 4 anaplastic ependymomas (WHO Grade III). The MIB-1 proliferation index was
      significantly higher in tumors diagnosed as anaplastic ependymoma (P < .001),
      with a moderate level of correlation (Kendall's tau-b = 0.557, asymptotic
      standard error = 108). In addition, one ependymoma (WHO Grade II) not considered
      overtly anaplastic by routine histologic criteria showed a high MIB-1 labeling
      index, suggesting that the MIB-1 proliferation index might be a more objective
      indicator of tumor grade. The remaining WHO Grade I and Grade II ependymomas
      showed low proliferative activity. bcl-2 oncoprotein expression was identified in
      all of the four myxopapillary and in both papillary ependymomas. An additional
      observation was the correlation of p53 expression with increasing WHO grade.
      These data suggest that high MIB-1 and p53 immunolabeling might be objective
      indicators of high grade in ependymomas that do not otherwise meet routine
      histologic criteria for high-grade ependymoma. Subsequent clinicopathologic
      analyses will be important in assessing whether these markers are useful as
      independent predictors of survival.

PMID- 9619601
TI  - Hepatitis C viral genome in a subset of primary hepatic lymphomas.
AB  - Hepatitis B virus (HBV) and hepatitis C virus (HCV) are not only hepatotropic but
      possibly hematotropic. Recent studies showed the presence of HBV in lymphoma
      cells of extrahepatic origin. In the current study, we examined the presence of
      HBV DNA and HCV RNA in the tumor tissues of nine patients with primary hepatic
      lymphoma (PHL). Immunohistochemical study using polyclonal anti-HCV antibody was
      possible in four cases. The age of the patients ranged from 45 to 78 years
      (median, 58 yr), with a male-to-female ratio of 2:1. A history of chronic
      hepatitis was found in three patients and of cirrhosis in one. Histologically,
      all of the cases were non-Hodgkin's lymphoma of B-cell phenotype, with a diffuse
      large cell type being the most common. Polymerase chain reaction using both the S
      and X region primers failed to detect HBV DNA in the lymphoma tissues. The HCV
      genome was detected by in situ hybridization in the tumor cells but not in the
      surrounding hepatocytes in the one case of cirrhosis, which probably resulted
      from a blood transfusion more than 20 years previous; immunohistochemical
      analysis revealed positive staining for anti-HCV antibody in the cytoplasm of
      lymphoma cells in this case. In two cases, positive signals were found only in
      the hepatocytes surrounding the lymphoma. This is the first report showing the
      presence of the HCV genome in the lymphoma cells of PHL. HCV could be involved in
      development of PHL directly or via exogenic antigenic stimulus from HCV-infected
      hepatocytes.

PMID- 9619602
TI  - Post-transplantation lymphoproliferative disorder of the NK-cell type: a case
      report and review of the literature.
AB  - Post-transplantation lymphoproliferative disorders (PTLDs) are primarily B-cell
      disorders that are thought to be Epstein-Barr virus (EBV) driven and that can
      occur months to years after solid organ or bone marrow transplantation. A small
      percentage of cases have also been shown to be T-cell phenotype, but a PTLD of NK
      cell type has not been previously described. We report here the case of a renal
      transplant recipient in whom a clinically aggressive, histologically monomorphic
      PTLD developed that was documented to be of an NK-cell phenotype according to
      paraffin section and flow cytometric immunophenotyping. Molecular-genetic
      analysis showed the PTLD to contain germline immunoglobulin heavy, kappa light
      chain, and T-cell receptor beta and gamma genes. Studies for EBV failed to
      demonstrate the presence of viral infection in tumor cells. Clinical follow-up
      showed a rapidly fatal course. To our knowledge, this is the first reported case
      of an EBV-negative PTLD of true NK-cell type.

PMID- 9619603
TI  - The clonal relationship between nodular sclerosis Hodgkin's disease with a clonal
      Reed-Sternberg cell population and a subsequent B-cell small noncleaved cell
      lymphoma.
AB  - We evaluated the clonal relationship between a case of nodular sclerosis
      Hodgkin's disease (NSHD) and a small noncleaved cell (SNC) lymphoma that
      subsequently developed. Single Hodgkin and Reed-Sternberg (H-RS) cells were
      isolated from immunostained sections of the NSHD by micromanipulation, and the
      immunoglobulin heavy chain gene (IgH) complementarity determining region (CDR)
      III of the cells was amplified by the polymerase chain reaction (PCR). A clonal
      population of H-RS cells was found in the NSHD tumor. The nucleotide sequence of
      the clonal H-RS cells was compared with the clonal IgH CDRIII sequence from the
      SNC lymphoma. The two sequences were found to be unrelated. In addition, clone
      specific primers and probes were designed from the two clonal IgH CDRIII
      sequences and used to investigate the presence of the respective clonal
      population in the NSHD tumor. The latter studies confirmed the presence of a
      major clonal H-RS cell population, as detected by the single cell assay, but
      cells corresponding to the SNC clone were not demonstrable by this highly
      sensitive technique. These findings suggest that the SNC arising in this case
      represents the development of the second neoplasm clonally unrelated to the
      preceding NSHD. They also support the recent findings that the H-RS cells in
      classical HD consist of a clonal population of B cells.

PMID- 9619604
TI  - Giant cell fibroblastoma associated with dermatofibrosarcoma protuberans: a case
      report.
AB  - A case of congenital giant cell fibroblastoma (GCF) associated with
      dermatofibrosarcoma protuberans (DFSP) in a 1.5-year-old girl is reported. The
      GCF component was characterized by a mixed proliferation of fibroblastic cells
      and multinucleated giant cells and sinusoid-like spaces. The DFSP component,
      which was spatially distinct from the GCF region, was composed of short spindle
      shaped cells arranged in a storiform pattern. Mitotic figures were frequently
      identified in the DFSP area but not in the GCF region. Immunohistochemically,
      tumor cells in both components were positive for CD34. The Ki-67 labeling index
      of the DFSP area (4.9%) was markedly higher than that of the GCF (0.5%).
      Ultrastructurally, spindle-shaped tumor cells in both components, as well as
      giant cells, were fibroblastic cells that frequently exhibited multilobulated
      nuclei. This case illustrates the close histogenetic relationship between GCF and
      DFSP, although the degree of proliferative activity is much higher in the DFSP
      area.

PMID- 9619605
TI  - Hamartoma of mature cardiac myocytes: a case report.
AB  - A 24-year-old man presented with hypertension, palpitations, and premature atrial
      and ventricular contractions. A mass was discovered in the distal
      interventricular septum that was composed of dense collagenous tissue, fat, and
      disorganized, hypertrophic, mature cardiac myocytes indicative of a cardiac
      hamartoma. This entity has only rarely been reported and must be distinguished
      from the much more common rhabdomyoma and from oncocytic cardiomyopathy, which is
      also referred to as "cardiac hamartoma."

PMID- 9619606
TI  - Recommendations for reporting resected pancreatic neoplasms. The Association of
      Directors of Anatomic and Surgical Pathology.

PMID- 9619608
TI  - The ASE Web page.

PMID- 9619607
TI  - Correspondence re: Arber JM, Weiss LM, Chang KL, Battifora H, Arber DA. The
      effect of decalcification on in situ hybridization. Mod Pathol 1997;10:1009-14.

PMID- 9619609
TI  - How to start browsing the Web.

PMID- 9619610
TI  - Noninvasive functional assessment of left internal mammary artery grafts by
      transcutaneous Doppler echocardiography.
AB  - A noninvasive method to assess left internal mammary artery (LIMA) patency and
      function would be useful because this vessel is frequently used for
      revascularization of the left anterior descending coronary artery. The purpose of
      this study was to assess the feasibility of measuring changes in LIMA velocities
      by transcutaneous Doppler during dipyridamole-induced vasodilation. Twenty-five
      patients with a LIMA graft anastomosed to the left anterior descending coronary
      artery were studied at least 1 month after surgery by the use of a 5 MHz
      transducer placed in the left supraclavicular fossa. Doppler velocity parameters
      were measured at baseline and after intravenous administration of dipyridamole.
      Dipyridamole increased mean velocity by 127% +/- 54% (p < 0.001),
      systolodiastolic velocity time integral by 89% +/- 31% (p < 0.001), and diastolic
      to-systolic peak velocity ratio from 0.7 +/- 0.3 to 1.2 +/- 0.4 (p < 0.001). The
      dipyridamole-to-baseline mean velocity ratio was 2.3 +/- 0.5. We conclude that it
      is possible to measure dipyridamole-induced changes in LIMA flow velocities and
      thus obtain an index of LIMA blood velocity reserve by transcutaneous Doppler
      echocardiography.

PMID- 9619611
TI  - Transthoracic Doppler echocardiography of normally originating coronary arteries
      in children.
AB  - Transthoracic Doppler color flow and spectral velocity patterns of normal
      coronary arteries in children have not been well studied. We designed this study
      to evaluate coronary artery flow velocity characteristics in normal and
      hypertrophied hearts. Sixty-eight children with optimal two-dimensional
      echocardiographic images of the left coronary artery (LCA) and right coronary
      artery (RCA) were prospectively studied. The heart was normal in 45 children, and
      23 had left and/or right ventricular hypertrophy assessed by echocardiography
      (mean age 5.8 versus 5.2 years, p = NS). Color flow signals were detected in the
      LCA in 63(92%) of the 68 children studied, and pulsed Doppler spectral waveforms
      were recorded in 47 (69%). The latter were recorded in 26 (58%) of 45 normal
      children and in 21 (91%) of 23 children with left ventricular hypertrophy.
      Diastolic RCA flow signals were detected mostly in those with right ventricular
      hypertrophy (10 of 10). Higher levels of LCA maximum diastolic velocity (42 +/-
      23 versus 24 +/- 6 cm/sec, p = 0.0004), increased diastolic flow (16 +/- 15
      versus 6 +/- 4 ml/min, p = 0.01), and delayed time to peak diastolic velocity
      expressed as a percentage of diastolic spectral duration (38% +/- 14% versus 20%
      +/- 8%, p = 0.0001) were observed in children with left ventricular hypertrophy
      than in those in normal children. A strong correlation was present between
      Doppler-derived LCA flow and left ventricular mass/m2 (r = 0.7, p = 0.001). In
      normal hearts, LCA spectral velocity pattern did not change with increasing age,
      but the time velocity integral became progressively larger, resulting in a strong
      correlation with weight (p < 0.001, r = 0.78). This study demonstrates (1) LCA
      flow signals can be detected and quantitated in the majority of children with and
      those without left ventricular hypertrophy. (2) Left ventricular hypertrophy is
      associated with increased LCA flow, higher diastolic velocity, and delayed peak
      diastolic velocity. (3) RCA flow signals are mostly detected when there is right
      ventricular hypertrophy. Studies on larger groups of patients are needed to
      further confirm our observations and to enhance understanding of coronary artery
      flow reserve.

PMID- 9619612
TI  - Effect of blood and microbubble oxygen and nitrogen content on perfluorocarbon
      filled dextrose albumin microbubble size and efficacy: in vitro and in vivo
      studies.
AB  - We hypothesized, on the basis of in vitro observations, that a higher oxygen
      partial pressure within perfluorocarbon-containing microbubbles (PCMB) would
      enhance inward nitrogen diffusion after venous injection, leading to improved
      myocardial contrast. The in vitro studies measured PCMB size and concentration
      after injection into arterial blood that was obtained during inhalation of either
      room air or 100% oxygen. We then compared the myocardial contrast produced from
      PCMB sonicated in the presence of either a nitrogen-free environment (100%
      oxygen) or room air in three closed chest dogs. PCMB exposed to oxygenated blood
      in vitro were significantly smaller after insonation than PCMB exposed to
      arterial blood obtained during room air inhalation, confirming the important role
      of dissolved nitrogen in stabilizing PCMB size. In vivo studies demonstrated that
      intravenous PCMB sonicated with 100% oxygen produced significantly greater
      anterior and posterior myocardial contrast than PCMB sonicated in the presence of
      room air.

PMID- 9619613
TI  - Increasing the dose and rate of Albunex infusion leads to superior left
      ventricular contrast effect.
AB  - In routine clinical use, the efficacy of Albunex in producing clinically useful
      opacification may be lower than in initial clinical studies. We hypothesized that
      increasing either the rate of injection or amount of Albunex administered would
      increase left ventricular opacification. Fifty adult volunteers were each
      injected with Albunex in five volume/rate combinations. Blinded reviewers
      evaluated left ventricular opacification and endocardial border delineation
      compared with the baseline (noncontrast) echocardiogram. In addition, captured
      digitized images were analyzed with video-densitometric techniques. Injected at
      the highest volume/rate tested (20 ml at 3.0 ml/sec), Albunex provided the
      greatest improvement in left ventricular opacification, endocardial border
      delineation, and quality of the echocardiogram. The administration of Albunex
      caused no serious adverse events at any volume/rate regimen tested. Our data
      indicate that faster injection rates and larger dose volumes than those currently
      recommended by the package insert significantly improve Albunex ultrasound
      contrast without compromising safety.

PMID- 9619614
TI  - Outpatient two-dimensional echocardiography-guided pericardiocentesis.
AB  - Two-dimensional echocardiography-guided pericardiocentesis is an accepted, safe,
      and cost-effective procedure. Carefully selected patients can be treated with
      this technique in an outpatient setting. A consecutive series of outpatient
      echocardiography-directed pericardiocentesis performed for diagnostic or
      therapeutic indications is described. Appropriate technique and precautions are
      discussed.

PMID- 9619615
TI  - Impaired systolic blood pressure response to dobutamine stress testing: a marker
      of more severe functional abnormalities in patients with myocardial infarction.
AB  - Dobutamine-induced hypotension has been disregarded as a marker of more severe
      functional abnormalities in patients with suspected coronary artery disease.
      However, its functional significance in patients with myocardial infarction has
      not been studied. The aim of this study was to define the predictors of systolic
      blood pressure (SBP) response to dobutamine in patients with previous myocardial
      infarction. Dobutamine stress (up to 40 microg/kg per minute) echocardiography
      was performed in 326 patients with prior myocardial infarction referred for
      evaluation of myocardial ischemia. A 16-segment, four-grade score model was used
      to assess left ventricular function. Wall motion score index was derived by
      summation of wall motion score divided by 16. SBP and heart rate increased from
      rest to peak dobutamine stress (127 +/- 22 vs 134 +/- 27 mm Hg and 72 +/- 14 vs
      122 +/- 24 bpm, p < 0.00001 in both). An increase of SBP > or = 30 mm Hg occurred
      in 50 patients (15%). By multivariate analysis, independent predictors of failure
      of SBP increase were higher peak wall motion score index (p < 0.001), higher
      resting SBP (p < 0.01), and medication with calcium channel blockers (p < 0.05).
      SBP drop > or = 20 mm Hg occurred in 54 patients (17%). Independent predictors of
      SBP drop were higher resting wall motion score index (p < 0.001), higher resting
      SBP (p < 0.0001), and older age (p < 0.05). In patients with myocardial
      infarction, left ventricular function and baseline systolic blood pressure are
      powerful predictors of SBP response to dobutamine stress testing.

PMID- 9619616
TI  - Assessment of left ventricular systolic wall motion velocity with pulsed tissue
      Doppler imaging: comparison with peak dP/dt of the left ventricular pressure
      curve.
AB  - To assess the usefulness of the tissue Doppler imaging variables for the
      evaluation of left ventricular (LV) systolic function, we compared variables
      obtained by the pulsed Doppler method with the LV ejection fraction (%EF) and the
      maximum value for the first derivative of LV pressure (peak dP/dt). We examined
      65 patients, including 15 patients with noncardiac chest pain, 15 with ischemic
      heart disease, 15 with dilated cardiomyopathy, 10 with hypertensive heart
      disease, and 10 with asymmetric septal hypertrophic cardiomyopathy. The
      subendocardial systolic wall motion velocity patterns were recorded for LV
      posterior wall and ventricular septum in the parasternal LV long-axis view. The
      peak dP/dt was significantly lower in the hypertensive heart disease,
      hypertrophic cardiomyopathy, and dilated cardiomyopathy groups. The peak systolic
      velocity was lower and the time from the electrocardiographic Q wave to the peak
      of the systolic wave for the posterior wall was longer in the hypertensive heart
      disease (5.9 +/- 0.5 cm/sec and 215 +/- 21 msec, respectively), hypertrophic
      cardiomyopathy (6.2 +/- 0.9 cm/sec and 217 +/- 17 msec, respectively), and
      dilated cardiomyopathy (5.2 +/- 0.8 cm/sec and 235 +/- 26 msec, respectively)
      groups than in the noncardiac chest pain (7.7 +/- 0.9 cm/sec and 187 +/- 24 msec,
      respectively) and the ischemic heart disease (7.6 +/- 0.8 cm/sec and 184 +/- 22
      msec, respectively) groups. In all groups, the peak systolic velocity and the
      time from the electrocardiographic Q wave to the peak of the systolic wave for
      the posterior wall correlated directly and inversely, respectively, with the %EF
      (r = 0.59, p < 0.0001; r = -0.59, p < 0.0001) and the peak dP/dt (r = 0.75, p <
      0.0001; r = -0.68, p < 0.0001). Both tissue Doppler variables for the ventricular
      septum did not correlate with the %EF but roughly correlated with peak dP/dt. We
      conclude that the systolic LV wall motion velocity parameters obtained by pulsed
      tissue Doppler imaging may be useful for noninvasive evaluation of global LV
      systolic function in patients with no regional asynergy.

PMID- 9619617
TI  - Short deceleration time of mitral inflow E velocity: prognostic implication with
      atrial fibrillation versus sinus rhythm.
AB  - The present study retrospectively identified 367 patients who had restrictive
      physiology as defined by deceleration time < or = 130 msec; 293 were in sinus
      rhythm (SR) (194 men and 99 women; mean age 64 +/- 14 years) and 74 were in
      atrial fibrillation (AF) (51 men and 23 women; mean age 72 +/- 11 years; p <
      0.001). Both groups had similar underlying diagnoses and no significant
      difference in Doppler indices (E wave, 96 +/- 23 vs 99 +/- 22 cm/sec in SR and
      AF, respectively; deceleration time, 116 +/- 12 vs 116 +/- 13 msec; and left
      ventricular outflow tract time velocity integral, 14.8 +/- 4.8 vs 14.5 +/- 4.4
      cm). Left ventricular ejection fraction was significantly lower in SR patients
      (29% +/- 16% vs 39% +/- 20%; p = 0.0003). There were 120 deaths (41%) in the SR
      group and 35 (47%) in the AF group (median follow-up for both groups, 2.2 years).
      Restrictive physiology as defined by Doppler echocardiography (deceleration time
      < or = 130 msec) appears to predict a similar poor prognosis with AF as with SR.

PMID- 9619618
TI  - Age independence of the difference in duration of pulmonary venous atrial
      reversal flow and transmitral A-wave flow in normal subjects.
AB  - Aging influences pulmonary venous flow and mitral inflow velocities. The duration
      of pulmonary venous atrial reversal flow exceeds that of the mitral inflow A wave
      in patients with left ventricular end-diastolic pressures greater than 15 mm Hg.
      The objective of this study was to investigate the effect of age on the
      difference between the duration of pulmonary venous atrial reversal flow and that
      of the mitral inflow A wave in a large number of normal individuals. Pulsed wave
      Doppler transthoracic echocardiograms of the pulmonary venous flow and the
      transmitral inflow with respiratory monitoring were made of 72 normal volunteers
      (40 women) ranging in age between 23 and 84 years. The differences in the
      durations of pulmonary venous atrial reversal flow and mitral inflow A wave were
      measured and their correlation with age assessed. Age was not highly correlated
      with the duration of pulmonary venous atrial reversal flow (r = 0.25) nor the
      duration of the mitral inflow A wave (r = 0.33). The duration of pulmonary venous
      atrial reversal flow exceeded the duration of the mitral inflow A-wave flow only
      in three (4%) of 72 subjects, and age was not related to the index in this group
      (r = -0.16; p = 0.19). The difference in durations was not significantly affected
      by the phase of respiration. Men had higher values on all measurements than
      women. The difference between the pulmonary venous atrial reversal duration and
      the mitral inflow A-wave duration is independent of age and thus may be used as a
      reliable index of left ventricular end-diastolic pressure, even in elderly
      patients.

PMID- 9619619
TI  - Reference Doppler echocardiographic values for St. Jude Medical, Omnicarbon, and
      Biocor prosthetic valves in the aortic position.
AB  - The objectives of the present investigation were (1) to describe Doppler
      echocardiographic findings for mechanical and biologic aortic valves at an early
      stage after operation and later in a stable phase and (2) to study the changes
      occurring between these investigations. Patients (n = 213) who received a
      mechanical (St. Jude Medical, Omnicarbon) or a biologic (Biocor) valve were
      studied by Doppler echocardiography within the first week (baseline, n = 203) and
      after 2 years (late, n = 172). The comparison of baseline with late investigation
      (mean +/- SD) showed an increase in systolic blood pressure (137 +/- 18.5 to 154
      +/- 20.6 mm Hg, p = 0.0001, n = 112), reduction of heart rate (85 +/- 15.3 to 74
      +/- 12.0 beats/min, p = 0.0001, n = 141) and increase in stroke volume (59 +/-
      20.6 to 77 +/- 19.8 ml, p = 0.0001, n = 132). Prosthetic Doppler
      echocardiographic findings demonstrated a reduction in blood flow velocity in the
      left ventricular outflow tract (VLVOT, 1.10 +/- 0.25 to 0.96 +/- 0.23 m/sec, p =
      0.0001, n = 146) reduction in peak velocity (Vmax 2.72 +/- 0.53 to 2.59 +/- 0.54
      m/sec, p = 0.02, n = 150), reduction in mean pressure gradient (deltaPmean, 18.4
      +/- 7.2 to 16.3 +/- 7.3 mm Hg, p = 0.004) and an increase in velocity index
      (Vmax/VLVOT, 2.56 +/- 0.62 to 2.67 +/- 0.60, p = 0.003, n = 144). The standard
      deviations of difference between baseline and late investigation expressed as
      percentage of mean were 25% for VLVOT, 20% for Vmax, 44% for deltaPmean, and 25%
      for velocity index. In conclusion, this large reference base provides data that
      should be useful for the clinician evaluating patients with prosthetic valves
      early after valve replacement as well as at a later stage. When valve dysfunction
      is suspected a previous investigation for comparison is helpful, and our data
      describe the changes that normally may be seen between an early baseline and a
      late investigation.

PMID- 9619620
TI  - Evaluation of a bileaflet aortic valve prosthesis before and after thrombolytic
      tissue plasminogen activator therapy by continuous wave Doppler ultrasound.
AB  - Thrombotic obstruction of mechanical prosthetic valves is a frequently
      encountered cause of prosthetic valve dysfunction, which can result in stenosis
      and regurgitation. We present a case of thrombotic obstruction of a bileaflet
      mechanical aortic valve prosthesis that resulted in severe stenosis and
      regurgitation. Considering the known risk factors associated with both surgical
      and thrombolytic treatments, a decision was made to use tissue plasminogen
      activator therapy to relieve the burden of the thrombotic valvular obstruction.
      In this case review, we use continuous wave Doppler to demonstrate recovery of
      normal valve function despite suboptimal two-dimensional imaging.

PMID- 9619621
TI  - Congenital duplication of the tricuspid valve presenting as a circumscribed
      obstructive mass in the right ventricular outflow tract.
AB  - Congenital duplication of the tricuspid valve is a rare condition. We present a
      case of a 32-year-old man with an increase in intensity of a long-standing heart
      murmur and intermittent palpitations. The murmur was evaluated by transthoracic
      and transesophageal echocardiography that identified a mass in the right
      ventricle and right ventricular outflow tract resulting in partial obstruction of
      the right ventricular outflow tract. This mass was determined to be congenital
      duplication of the tricuspid valve by histologic examination after surgical
      excision.

PMID- 9619622
TI  - Acquired ventricular septal defect and mitral insufficiency without pericardial
      effusion after stab wound to the chest.
AB  - Echocardiography has a role in the management of acute complications of
      penetrating cardiac trauma. We report the case of a 30-year-old man who sustained
      a stab wound to the chest. In this case a traumatic perforation of the
      ventricular septum and the anterior leaflet of the mitral valve caused by a knife
      occurred without pericardial effusion. The diagnosis was made by transthoracic
      echocardiography. The ability of transesophageal echocardiography to delineate
      the intracardiac injuries more precisely helped to guide the surgical procedure.

PMID- 9619623
TI  - Periaortic fat pad mimicking an intramural hematoma of the thoracic aorta:
      lessons for transesophageal echocardiography.
AB  - We report a patient whose clinical and echocardiographic findings were compatible
      with a diagnosis of aortic intramural hematoma, but magnetic resonance imaging
      demonstrated a prominent and localized periaortic deposit of fat as the cause of
      the transesophageal echocardiographic appearance. This is a significant caveat
      that must be borne in mind when interpreting echocardiographic images obtained in
      patients with suspected intramural aortic hematomas.

PMID- 9619624
TI  - Unilateral pulmonary edema during transesophageal echocardiography.
AB  - Transesophageal echocardiography is considered to be a relatively safe procedure,
      the complications of which are well known and include probe-related and procedure
      related complications. Congestive heart failure rarely occurs. Unilateral
      pulmonary edema is relatively uncommon and to the best of our knowledge has never
      been reported in association with transesophageal echocardiography. Herein we
      describe an unusual case of unilateral pulmonary edema that developed during the
      course of transesophageal echocardiography.

PMID- 9619625
TI  - Transesophageal echocardiography in a case of cardiac compression: was it
      therapeutic?
AB  - Cardiac compression is a potentially life-threatening complication of heart
      surgery. This syndrome often has atypical manifestations, challenging our ability
      to make a rapid diagnosis and to institute emergent, life-saving treatment. We
      recently evaluated one such patient who showed cardiac compression caused by an
      unusual paracardiac mass. The addition of transesophageal echocardiography to the
      usual transthoracic study may have played more than just a diagnostic role in
      this case.

PMID- 9619626
TI  - Double-strand break repair mediated by DNA end-joining.
AB  - DNA double-strand breaks formed by ionizing irradiation or other stresses are
      repaired by homologous recombination or DNA end-joining. This review focuses on
      the mechanism of double-strand break repair mediated by DNA end-joining, in which
      many factors have recently been identified. After DNA double-strand breakage, DNA
      end-joining takes place between the DNA ends that have nonhomologous sequences or
      very short regions ofhomology. The broken DNA is repaired if the DNA end-joining
      occurs in the same molecule, while it causes chromosome aberrations such as
      deletions, insertions, translocations and inversions if it occurs between
      different molecules. Rad50 and its relatives, Ku-proteins, DNA ligase VI and
      silencing factors, are involved in DNA end-joining in yeast and mammalian cells.
      These findings led us to propose a model in which the formation of a
      heterochromatin-like complex at broken ends is an important element in DNA end
      joining.

PMID- 9619627
TI  - Rad52 forms ring structures and co-operates with RPA in single-strand DNA
      annealing.
AB  - BACKGROUND: The RAD52 epistasis group in Saccharomyces cerevisiae is involved in
      various types of homologous recombination including recombinational double-strand
      break (DSB) repair and meiotic recombination. A RecA homologue, Rad51, plays a
      pivotal role in homology search and strand exchange. Genetic analysis has shown
      that among members of its epistasis group, RAD52 alone is required for
      recombination between direct repeats yielding deletions. Very little has been
      discovered about the biochemical roles and structure of the Rad52 protein.
      RESULTS: Purified Rad52 protein binds to both single-stranded DNA (ssDNA) and
      double-stranded DNA (dsDNA). Electron microscope observations revealed that Rad52
      molecules form multimeric rings. An increase in the intensity of fluorescence
      when Rad52 is bound to epsilonDNA showed an alteration of the structure of ssDNA.
      RPA was binding to Rad52 and enhanced the annealing of complementary ssDNA
      molecules. This enhancement was not observed in Escherichia coli SSB protein or
      T4 phage gp32 protein. CONCLUSION: Rad52 forms a ring-like structure and binds to
      ssDNA. Its structure and DNA binding properties are different from those of
      Rad51. The interaction of Rad52 with RPA plays an important role in the
      enhancement of annealing of complementary ssDNAs. We therefore propose that Rad52
      mediates the RAD51-independent recombination through an ssDNA annealing, assisted
      by RPA.

PMID- 9619628
TI  - Identification of sna41 gene, which is the suppressor of nda4 mutation and is
      involved in DNA replication in Schizosaccharomyces pombe.
AB  - BACKGROUND: The replication licensing factor limits DNA replication to once in a
      cell cycle and is thought to contain MCM proteins as its component parts. Six MCM
      subtypes have been identified in various species. These MCM proteins are thought
      to bind each other to make a heteromeric complex. The Nda4 protein of
      Schizosaccharomyces pombe is one of the MCM proteins and is involved in DNA
      replication. RESULTS: The suppressor mutant of nda4 was isolated and the mutant
      gene was named sna41. The sna41-912 mutant demonstrated the ts phenotype, with an
      elongated cell shape at the restrictive temperature. Cells with 1C DNA content
      accumulated 2 h after shifting up to the restrictive temperature. This result
      suggests that sna41 is also involved in DNA replication. The sna41 genomic clone
      was isolated by a complementation of the ts phenotype of the mutant strain and
      was sequenced. The sna41 gene encodes a protein of 638 amino acids, which has low
      homology with CDC45 in S. cerevisiae. The gene disruption analysis showed that
      sna41 gene is essential for viability. CONCLUSIONS: The S. pombe sna41 mutation
      suppresses the nda4-108 mutation. Sna41 is involved in DNA replication and may
      play some roles in the regulation of DNA replication by the MCM proteins.

PMID- 9619629
TI  - A new mammalian period gene predominantly expressed in the suprachiasmatic
      nucleus.
AB  - BACKGROUND: In mammals, two possible clock genes (Clock, Per1) have very recently
      been reported. mPer1 (the first identified mouse period gene), in particular,
      shows a circadian expression in suprachiasmatic nuclei (SCN), the mammalian
      circadian centre. However, only mPer1 and Clock as clock components may not be
      sufficient to understand all the events in circadian oscillation and entrainment.
      RESULTS: A mammalian period complementary DNA, mPer2, has been isolated from the
      mouse brain. The amino acid sequence of mPer2 is similar to mPer1 and Drosophila
      Period (dPer), indicating that mPer2 is a member of the family which contains
      mPer1, itself a homologue of dPer. mPer2 mRNA is predominantly expressed in SCN.
      A robust circadian rhythmic expression in the SCN supports the view that mPer2 is
      a clock gene. mPer2 is strongly expressed at the subjective afternoon in constant
      darkness, distinct from a morning-phase clock mPer1. Our precise quantitative in
      situ hybridizations have revealed that the peak expression of mPer2 transcripts
      is delayed by 8 h in LD (light-dark) or 4 h in DD (dark-dark) conditions when
      compared to mPer1. A short brief light exposure at the early subjective night,
      prompting a phase-shift in locomotor rhythms, induces a transient increase of
      mPer2 transcripts with delayed onset, as compared to mPer1 mRNA induction.
      Furthermore, mPer2 is co-expressed with mPer1 in single SCN cells. CONCLUSIONS:
      Mammalian period genes show molecular heterogeneity, each of which is composed of
      a different oscillator, and may serve to establish stable circadian rhythms in
      mammalian oscillating cells.

PMID- 9619630
TI  - Myosin II activation promotes neurite retraction during the action of Rho and Rho
      kinase.
AB  - BACKGROUND: The Rho small GTPase regulates myosin II activity through the
      phosphorylation of the myosin light chain (MLC) by activating Rho-kinase, which
      is a target of Rho. Several lines of evidence point to an important role of Rho
      in the action of lysophosphatidic acid (LPA) and thrombin in provoking neurite
      retraction in N1E-115 neuroblastoma cells. RESULTS: Here we examined whether Rho
      kinase and myosin II are involved in neurite retraction in N1E-115 cells. We
      showed that the expression of constitutively active forms of Rho-kinase induced
      neurite retraction in NIE-115 cells and MLC phosphorylation in NIH 3T3 cells,
      whereas the expression of dominant negative forms of Rho-kinase inhibited the LPA
      induced neurite retraction in N1E-115 cells and the serum-induced MLC
      phosphorylation in NIH 3T3 cells. The expression of mutant MLCT18D,S19D
      (substitution of Thr and Ser by Asp), which is known to lead to the activation of
      myosin ATPase and a conformational change of myosin II when reconstituted with
      myosin heavy chains in vitro, also promoted neurite retraction. CONCLUSION: These
      results indicate that Rho-kinase is involved in the LPA-induced neurite
      retraction downstream of Rho, and that myosin II activation promotes neurite
      retraction downstream of Rho and Rho-kinase.

PMID- 9619631
TI  - Characterization of the C. elegans gap-2 gene encoding a novel Ras-GTPase
      activating protein and its possible role in larval development.
AB  - BACKGROUND: The Ras signalling pathway plays several important roles in the
      development of the nematode Caenorhabditis elegans. So far, two types of Ras
      GTPase activating proteins (Ras-GAPs) have been identified in this organism. To
      aid the study of the regulation and function of the Ras pathway, we set out to
      isolate a new GAP gene from C. elegans by transcomplementation of the fission
      yeast gap1 mutant. RESULTS: We isolated a C. elegans cDNA that encoded a protein
      which was similar to, but not exactly homologous with mammalian p120 Ras-GAP.
      This gene, named gap-2, generated at least nine distinct mRNA species through
      transcription from different promoters and subsequent alternative splicing
      involving 25 exons. These isoforms were differentially expressed among tissues. A
      deletion of gap-2 caused no obvious phenotype by itself, but a loss of gap-2
      function could suppress larval lethality in both let-23 and let-60 reduction-of
      function mutants, in which the Ras activity was lowered. CONCLUSIONS: C. elegans
      gap-2 encodes a novel Ras-GAP, which is similar to vertebrate p120 but which may
      constitute a new GAP subfamily. gap-2 mRNA isoforms arise by an unusually
      extensive variation in initiation sites and associated alternative splicing, and
      each isoform may play a distinct role in specific tissues. GAP-2 appears to
      function as a negative regulator of LET-60 Ras during larval development.

PMID- 9619632
TI  - Modulation of ICAM-1, VCAM-1 and HLA-DR by cytokines and steroids on HUVECs and
      human brain endothelial cells.
AB  - The in vitro effects of dexamethasone (Dx) and low and high-dose 6
      methylprednisolone (MP) on the expression of adhesion molecules ICAM-1,VCAM-1 and
      class II antigen HLA-DR on human brain endothelial cells (HBECs) was studied.
      HBECs were obtained from the surgical specimen of a multiple sclerosis patient
      undergoing brain surgery for vascular aneurysm. HBECs obtained from apparently
      normal brain capillaries of surgical specimens of two patients undergoing brain
      surgery for a meningioma and a low-grade glioma, respectively, were used as
      controls. The effect of steroids was studied both in the basal condition and
      after stimulation with proinflammatory cytokines (gamma-IFN and TNF-alpha). In
      order to detect possible endothelium local tissue specific differences, the
      experiment was repeated using human umbilical vein endothelial cells (HUVECs).
      Only high-dose MP was able to down-regulate TNF-alpha-induced VCAM-1 expression
      on endothelial cells.

PMID- 9619633
TI  - Examining potential drug therapies for muscular dystrophy utilising the dy/dy
      mouse: I. Clenbuterol.
AB  - As a potent promoter of muscle growth, clenbuterol has been proposed as a
      treatment for muscle wasting diseases. Thus, the effects of clenbuterol on
      dystrophic skeletal muscle was examined. Male dystrophic (dy/dy) mice aged 4-5
      weeks were treated with clenbuterol for 3 weeks, and the isometric contractile,
      fatigue and histochemical properties of the slow-twitch soleus and fast-twitch
      plantaris muscles measured. Muscles of dystrophic animals produced lower forces,
      contracted more slowly and exhibited greater fatigue resistance than age-matched
      normal animals. Dystrophic soleus muscles also had higher proportions of type I
      fibres than normal mice. Clenbuterol significantly reduced the natural death rate
      of dystrophic mice, as 3 of 11 untreated animals died prior to completion of the
      3-week experimental period, whereas none of the 9 clenbuterol-treated animals
      died. Clenbuterol treatment significantly increased the relative mass (P<0.001)
      and relative tetanic force production (P<0.01) of the soleus of dystrophic
      animals, most likely due to increases in protein accretion and improved
      regeneration. The plantaris of clenbuterol-treated dystrophic animals also
      exhibited higher mass (P<0.05) and higher absolute forces than untreated mice.
      The results from this study show that clenbuterol could be a valuable adjunct to
      treatments of muscle wasting diseases such as muscular dystrophy.

PMID- 9619634
TI  - Contrasting levels of p21ras activation and expression of neurofibromin in
      peripheral primitive neuroectodermal tumour and neuroblastoma cells, and their
      response to retinoic acid.
AB  - Ras protooncogenes encode small guanine nucleotide binding proteins (p21ras)
      activated by phosphorylation. Phosphorylation of p21ras is predominantly
      regulated by the GTPase activating proteins type 1 GAP120 and neurofibromin.
      Increased levels of p21ras-GTP (active) have been associated with increased cell
      growth and malignant transformation. In this study the relationship between
      p21ras, type 1 GAP120 and neurofibromin with growth and differentiation has been
      examined in neuroblastoma and peripheral primitive neuroectodermal tumour (pPNET)
      cell lines. The level of p21ras protein in neuroblastoma and pPNET cells was the
      same. However, the amount of p21ras-GTP bound was higher in pPNET than in
      neuroblastoma cells. This most likely reflects the absence of neurofibromin.
      Retinoic acid (RA)-induced differentiation and growth inhibition of neuroblastoma
      cells was associated with an increase in type 1 GAP120 and neurofibromin mRNA,
      and a decrease in p21ras-GTP. In pPNET cells levels of type 1 GAP120 but not
      neurofibromin mRNA were increased to similar levels to those in neuroblastoma
      cells. This was not associated with decreased p21ras-GTP, modulation of growth or
      change in morphology. In summary, constitutive activation of p21ras may have a
      role in the biology of pPNET cells. This may reflect abnormalities in
      neurofibromin expression, and could inpart explain why RA did not induce
      morphological differentiation and growth inhibition in pPNETs.

PMID- 9619635
TI  - Multiple sclerosis with mite antigen-specific IgE.
AB  - The total and mite antigen-specific IgE in the sera were measured in 60 patients
      with multiple sclerosis (MS) and 40 healthy controls by an enzyme-linked
      immunosorbent assay using two common mite antigens, Dermatophagoides farinae and
      Dermatophagoides pteronyssinus, in order to study the role of atopy in MS.
      Neither the total IgE level nor the frequency of mite antigen-specific IgE
      differed significantly between the MS patients (mean total IgE 162 U/ml, 42% mite
      IgE-positive) and healthy controls (mean total IgE 168 U/ml, 35% mite IgE
      positive). The MS patients with mite antigen-specific IgE showed a significantly
      higher level of serum total IgE (mean 293 U/ml, P=0.0005) and a higher frequency
      of atopic disorders (36%, P=0.0508) than did the MS patients without mite antigen
      specific IgE (mean total IgE 68 U/ml, atopic disorders 14%). The former group
      also showed a significantly higher frequency of male (P=0.0216), a younger age of
      onset (P=0.0081), a lower expanded disability status scale (EDSS) score (P=0.03)
      and a lower protein content in the cerebrospinal fluid (CSF) (P=0.0426) than the
      latter, while the duration of disease and a number of relapses did not differ
      significantly between the two groups. In addition, the mite IgE-positive MS
      showed a very low frequency of oligoclonal IgG bands in CSF (4%) and a
      significantly higher association of HLA-A24 (87.5%) than the healthy controls
      (45%). Therefore, the presence of IgE response to the mite antigens and atopy
      appeared to significantly lessen the severity of the disease and the immunologic
      abnormalities in MS.

PMID- 9619636
TI  - Late-onset sporadic progressive subcortical gliosis.
AB  - We report two sporadic cases of progressive subcortical gliosis (PSG) with onset
      after age 60. The presentation included slowly progressive dementia with memory
      loss, geographic disorientation, and personality change. Both were diagnosed
      clinically as Alzheimer's disease (AD) and both met NINCDS-ADRDA criteria for
      probable AD. Autopsy revealed generalized atrophy, predominantly involving the
      white matter of the frontal and temporal lobes. Microscopically, prominent
      fibrillary astrocytosis was present in the subcortical white matter and in the
      subpial and deep layers of the overlying cerebral cortex. Mild cortical neuron
      loss accompanied the gliosis, but no myelin loss was evident. Amyloid deposits
      and neuronal cytoskeletal inclusions were absent.

PMID- 9619637
TI  - Diagnosis of herpes simplex encephalitis by magnetic resonance imaging and
      polymerase chain reaction assay of cerebrospinal fluid.
AB  - The early diagnosis of herpes simplex encephalitis (HSE) is essential because
      early introduction of antiviral therapy can significantly reduce the mortality of
      this disease. Herpes simplex virus (HSV) DNA detection in cerebrospinal fluid
      (CSF) samples is a rapid, noninvasive, specific, and highly sensitive method for
      HSE diagnosis. Neurodiagnostic methods have also been studied for noninvasive
      diagnosis of HSE. Magnetic resonance imaging (MRI) seems to be the most sensitive
      of them but it has not been compared to PCR in terms of efficacy for HSE
      diagnosis. In this study, 17 patients with focal encephalitis were prospectively
      evaluated by PCR analysis of CSF samples and MRI examination. MRI lesions
      involving the inferomedial region of one or both temporal lobes were observed in
      all PCR-positive patients but one. No PCR-negative patient presented with the
      same pattern of MRI lesions. MRI was also important for the establishment of an
      alternative diagnosis in three of eight PCR-negative patients. Both methods
      should be routinely applied in the evaluation of presumed HSE cases.

PMID- 9619638
TI  - The spinal cord descending pathway for micturition: analysis in patients with
      spinal cord infarction.
AB  - We present three patients with urinary retention caused by spinal cord infarction
      of the deep white matter bilaterally within the ventral and lateral columns. This
      region corresponds to the watershed of the anterior spinal artery. We consider
      therefore that the descending pathway to the bladder lies in this area.

PMID- 9619639
TI  - Association of apolipoprotein E genotype and intronic polymorphism of the
      presenilin-1 gene with Alzheimer's disease in elderly Taiwan Chinese.
AB  - We studied the apoliprotein E (apo-E) allele frequencies and intronic
      polymorphism of the presenilin-1 (PS-1) gene in 55 patients with late-onset
      Alzheimer's disease (AD) and 93 age- and sex-matched controls. The apoE epsilon4
      allele frequency was significantly higher in the AD group than in the control
      group (0.255 versus 0.070, P<0.0001). The odds ratio for AD in individuals with
      either one or two epsilon4 alleles was 5.22 (95% confidence interval: 2.32
      11.70). The polymorphism within the region composing intron 3' to exon 8 of the
      PS-1 gene showed a similar distribution between AD patients and controls. This is
      the first study on the intronic polymorphism of the PS-1 gene in Chinese. Our
      results support an association between apoE epislon4 and AD in Chinese, but not
      between the intronic polymorphism of the PS-1 gene and AD. However, the allele
      frequency of apo-E epsilon4 among Chinese is lower than that among Caucasians.
      The interaction between apo-E and PS-1 genotypes is still unclear.

PMID- 9619640
TI  - Determinants of cognitive disorders in Autosomal Dominant Cerebellar Ataxia type
      1.
AB  - We assessed neuropsychological performances of 22 patients affected by Autosomal
      Dominant Cerebellar Ataxia type 1. All subjects completed a comprehensive battery
      of standardized tests requiring a verbal response, without time constraints. In
      order to verify the hypothesis that disease severity is the major factor in
      determining the cognitive status in this syndrome, patients were divided into
      three groups according to the severity of the clinical picture, as evaluated by
      the Inherited Ataxias Progression Scale (IAPS). Statistical analysis of the three
      groups' raw scores showed a significant decrement in patients with more severe
      clinical pictures on verbal short-term memory tasks. A similar trend, but not
      significant, was seen for general intelligence tests and verbal learning tasks.
      The decrement of verbal short-term memory could be related to motor speech
      problems. On the other hand, the decline of cognitive abilities over the course
      of the Autosomal Dominant Cerebellar Ataxia type 1 was not homogeneous enough to
      ensure statistically reliable trends. Therefore, this cross-sectional study
      suggests that the progression of the disease is a necessary factor in determining
      cognitive decline, but it is not sufficient. Other disease-related factors (age
      at onset, genotypic variety) could play a critical role: among these, the size of
      the expanded CAG repeats is significantly related to a decline of verbal
      intelligence and short-term memory in SCA2 patients.

PMID- 9619641
TI  - Intrathecal activation of the complement system and disability in multiple
      sclerosis.
AB  - BACKGROUND: The pathogenesis of multiple sclerosis (MS) appears to involve
      autoimmune phenomena in the central nervous system. Activation of the complement
      system is suggested to be involved in the pathogenesis. PATIENTS AND METHODS:
      Cerebrospinal fluid (CSF) and plasma samples from 65 patients with acute optic
      neuritis (ON) as a possible first symptom of MS (n=18), ON (n=16) or other
      attacks of clinically definite MS (n=15), and neurological control subjects
      (n=16) were studied. Activation of the initial part of the complement activation
      cascade was assessed by measuring activation of the C3 molecule; terminal
      activation of the complement cascade was assessed by measuring the terminal
      complement complex (TCC). Demyelination was estimated by the CSF concentration of
      myelin basic protein and neurological disability was assessed with the Kurtzke
      expanded disability status scale (EDSS) score. RESULTS: Activation of the initial
      part of the complement activation cascade occurred in each of the three groups of
      patients with demyelinating disease, but was not correlated to demyelination or
      disability. Increased concentrations of TCC were detected in patients with
      attacks of MS other than ON. The CSF concentrations of TCC, myelin basic protein
      (MBP) and neurological disability correlated significantly. The strongest
      correlation was between neurological disability and the CSF concentration of TCC
      (r=0.55, P=0.003). INTERPRETATION: Full activation of the complement cascade
      during attacks of MS may be restricted to patients with more advanced disease and
      is significantly correlated to the degree of neurological disability. This
      suggests that specific treatment with agents that inhibit complement activation
      may interfere with mechanisms involved in the pathogenesis of neurological
      disability in patients with MS.

PMID- 9619642
TI  - Natural killer cells in patients with Guillain-Barre syndrome.
AB  - We studied natural killer (NK) cell activity and NK cell number in peripheral
      blood of 20 patients with Guillain-Barre syndrome (GBS). NK cell activity
      obtained within 7 days after onset of neuropathic symptoms in patients with GBS
      was significantly decreased compared with that in 20 control subjects. NK cell
      activity was not well correlated with disease severity. After plasmapheresis, NK
      cell activity recovered to the normal range. Two-color flow cytometry showed that
      the NK cell subsets studied were quantitatively similar in GBS patients and
      controls.

PMID- 9619643
TI  - Molecular characterisation of Duchenne muscular dystrophy and phenotypic
      correlation.
AB  - Dystrophin gene was analysed in 32 unrelated DMD families (46 subjects: 32 index
      cases and 14 sibs) for the presence of deletions by mPCR for 27 exons and cDNA
      probes for the entire gene. Deletions were identified in 32 patients (25 index
      cases and seven sibs) from 25 families. The concordance between the clinical
      phenotype and 'reading frame' hypothesis was observed in 24 (75%) cases. Of
      these, nine patients were wheelchair bound between 8-12 years of age, nine (age
      range 5-10 years) showed progressive difficulty in walking and six (age range 1.6
      4 years) had onset of muscle weakness. One patient (CH), who was wheelchair bound
      at 12 years, the effect of mutation on the ORF could not be ascertained due to
      the presence of a junction fragment. Seven patients had inframe deletions of
      which four were wheelchair bound by the age of 13 years, and three (age range 5-7
      years) although, ambulatory had difficulty in walking. There were eight patients
      who showed no deletion, of which four became wheelchair bound by the age of 12
      years, four, though still ambulatory, were unable to run and tired easily.
      Correlation between phenotype and genotype of these DMD patients demonstrates
      that genetic studies of lymphocyte DNA may not always reflect the situation in
      the tissue involved in dystrophin, i.e. muscle. We describe a common dystrophin
      gene polymorphism in the Indian population with cDNA 11-14 that alters the Hind
      III restriction sites. Novel RFLPs were observed in 26 patients and their family
      members. Whether this is a polymorphism or, related to the diseased phenotype
      needs confirmation.

PMID- 9619644
TI  - Serum gelsolin and rhabdomyolysis.
AB  - We measured the serum gelsolin, actin-modulating protein, levels in five patients
      after rhabdomyolysis. We observed a tendency of serum gelsolin (83 kDa) to
      increase during the study period of 11 days. No intracellular gelsolin (80 kDa)
      was found in the serum, although it is abundant in muscle, and the destruction
      was severe as judged by other parameters. Serum gelsolin thus behaves differently
      in rhabdomyolysis than after acute tissue damage in other organs, such as liver
      necrosis and adult respiratory distress syndrome.

PMID- 9619645
TI  - The importance of electrodiagnostic studies in acute organophosphate poisoning.
AB  - Six patients with acute organophosphate pesticide poisoning in whom
      electrodiagnostic studies influenced or supported specific decisions in
      management are described. One patient was admitted to hospital with a diagnosis
      of acute alcoholic intoxication. Electrodiagnostic studies revealed single
      stimulus induced repetitive responses and decrement-increment responses at 30 and
      50 Hz repetitive nerve stimulation, findings that are indicative of a
      depolarization block due to inactivation of acetylcholinesterase at the motor end
      plate. The patient was subsequently treated as a case of acute organophosphate
      poisoning. The administration of edrophonium (0.1 mg) to another patient with
      normal neuromuscular transmission studies unmasked the latent
      electrophysiological abnormalities. Three instances are described in which
      electrodiagnostic studies were useful in predicting whether pralidoxime
      administration was likely to be useful and for how long was pralidoxime therapy
      to be continued. Phrenic nerve conduction study in one patient with impending
      respiratory failure revealed an unstimulable phrenic nerve. The potential role of
      phrenic nerve conduction studies and neuromuscular transmission studies in
      influencing decisions like intubation and mechanical ventilation is discussed.

PMID- 9619646
TI  - Late onset immunodeficiency in a patient with recurrent thymic carcinoma and
      myasthenia gravis.
AB  - The most common autoimmune disease associated with thymoma is myasthenia gravis.
      In addition, cellular and humoral immune defects have been frequently reported in
      association with thymic neoplasms. Here we report the case of a patient with
      myasthenia gravis receiving long-term immunosuppression with azathioprine and
      recurrent well-differentiated thymic carcinoma who developed CD4+ T-cell
      depletion and CNS cryptococcosis after multiple courses of chemotherapy and
      mediastinal irradiation. We hypothesize that in thymectomized patients bone
      marrow suppression and abrogation of the peripheral T-cell pool can result in a
      delayed T-cell regeneration due to the lack of functional thymic epithelium.

PMID- 9619647
TI  - Pyruvate dehydrogenase complex deficiency and altered respiratory chain function
      in a patient with Kearns-Sayre/MELAS overlap syndrome and A3243G mtDNA mutation.
AB  - Combined alteration of the pyruvate dehydrogenase complex and respiratory chain
      function is described in a 21 year-old male patient with overlapping MELAS
      (mitochondrial encephalomyopathy, lactic acidosis, and 'stroke-like' episodes)
      and Kearns-Sayre syndrome. Progressive external ophthalmoplegia, pigmentary
      retinopathy and right bundle branch block were present when he experienced the
      first 'stroke-like' episode at 18 years old. The A>G tRNALeu(UUR) point mutation
      at nucleotide 3243 of the mitochondrial DNA was predominant in muscle tissue
      (79%) and present, but at lower levels in fibroblasts (49%) and blood cells
      (37%). Biochemical analysis revealed diminished activities of pyruvate
      dehydrogenase (23%) and respiratory chain complexes I and IV (57%, respectively)
      in muscle, but normal activities in the fibroblasts. Immunochemical studies of
      the muscular pyruvate dehydrogenase components showed normal content of E1alpha,
      E1beta and E2 protein. Molecular screening of the E1alpha gene did not indicate a
      nuclear mutation. These observations suggest that mitochondrial DNA defects may
      be associated with altered nuclear encoded enzymes which are actively imported
      into mitochondria and constitute components of the mitochondrial matrix.
      Biochemical workup of mitochondrial disorders should not be restricted to the
      respiratory chain even if mitochondrial DNA mutations are present.

PMID- 9619648
TI  - Kleine-Levin syndrome and Parkinsonian symptoms--a case report.
AB  - We report the case of a 54-year-old male patient, who developed the symptoms of
      Kleine-Levin syndrome (KLS) at the age of fifty. Four years later Parkinsonian
      symptoms (PS) appeared. The possible relationship between both KLS and PS, e.g.
      regarding neuroendocrinological similarities, will be discussed to explain the
      subsequent onset of PS after the manifestation of KLS in this patient.

PMID- 9619650
TI  - Prove that rehabilitation works.

PMID- 9619649
TI  - Unusual association of multiple sclerosis and tomaculous neuropathy.
AB  - We describe two cases in which multiple sclerosis (MS) occurred in association
      with tomaculous neuropathy, presenting as chronic, distal sensorimotor
      polyneuropathy. In Case 1, monoclonal gammopathy of undetermined significance
      with monoclonal IgG lambda reactive against GM1 ganglioside, was also detected.
      The diagnosis of tomaculous neuropathy was established after sural nerve biopsy.
      Teased fibers examination revealed focal 'sausage-like' thickenings of the myelin
      sheaths in intact fibers and in fibers with segmental demyelination. Electron
      microscopy showed them to be due, mostly, to multiple windings of redundant
      myelin and concentric apposition of numerous lamellae, in contact with an intact
      myelin sheath. These are the first reported cases of tomaculous neuropathy in
      patients with MS. Whether the combination of the two conditions is purely
      coincidental or suggests the possible causal relation between MS and tomaculous
      neuropathy, is not certain.

PMID- 9619651
TI  - Clinical gait analysis in a rehabilitation context: some controversial issues.
AB  - OBJECTIVE: To determine the focus of clinical gait analysis in order to explain
      the observed mismatch between the available technology for movement analysis and
      the aims of clinical rehabilitation medicine. DESIGN: Literature search using two
      different interactive computerized search systems. OUTCOME MEASURES: The selected
      studies on clinical gait analysis were screened on the type of tasks they
      employed in the assessment of gait. The tasks were divided into impairment
      orientated and disability-orientated. RESULTS: The results indicated a dominance
      of simple motor tasks focusing at the level of impairments. In only 15 out of the
      96 reviewed articles were tasks used that were aimed at the level of
      disabilities. CONCLUSIONS: A gap exists between the conceptual frameworks used in
      clinical rehabilitation medicine and those used in clinical movement analysis.

PMID- 9619652
TI  - Visual gait analysis: the development of a clinical assessment and scale.
AB  - OBJECTIVES: To develop and evaluate a four-point scale visual gait assessment
      form, the Rivermead Visual Gait Assessment (RVGA), for clinical use with patients
      with neurological deficits. DESIGN: Preliminary clinical testing of reliability,
      validity and sensitivity to change. SETTING: Patients were recruited from the
      Rivermead Rehabilitation Centre (RRC), a centre specializing in rehabilitation
      for patients with neurological disease. PATIENTS: Ten inpatients were assessed by
      up to seven physiotherapists for the main reliability study, and eight different
      patients were also assessed by two raters one week apart. Twenty outpatients with
      multiple sclerosis (MS) who were receiving physiotherapy to improve their
      mobility and 27 inpatients with various neurological conditions were also
      assessed and the data used to examine validity, re iability and sensitivity to
      change. OUTCOME: The other comparative measures used were walking time, stride
      length, step length asymmetry, balance and the Rivermead Mobility Index. RESULTS:
      Inter-rater reliability between multiple raters was reasonable both for the
      global scores from the gait assessment form (Kendall's coefficient of
      concordance; p < 0.001), and for individual items (complete agreement occurred on
      63.8% of all observations). There was a significant correlation between the
      global RVGA score and the various criterion measures (r = 0.53-0.79; p < 0.001)
      and between change in the RVGA score and change in walking time in patients who
      received treatment (r = 0.68; p < 0.01). CONCLUSIONS: The RVGA provides the
      clinician with a clinical assessment of the quality of gait which may be used in
      conjunction with other measures to inform and monitor the value of physiotherapy
      treatment for people with MS and stroke, and possibly other neurological
      deficits.

PMID- 9619653
TI  - Leg extensor power and quadriceps strength: an assessment of repeatability in
      patients with osteoarthritic knees.
AB  - OBJECTIVE: To assess the repeatability of two muscle function measures -- leg
      extensor power (LEP) and isometric quadriceps force (IQF) -- in a population of
      patients with osteoarthritis of the knee. DESIGN: Repeat measures of LEP and IQF
      at 25 degrees and 50 degrees knee flexion were taken within seven days. Both legs
      were measured and a numerical rating scale was used to assess pain on the two
      occasions. SUBJECTS: Patients who were on a waiting list for a primary unilateral
      knee replacement for osteoarthritis were invited to take part in the study.
      SETTING: The physiotherapy department of a National Health Service Orthopaedic
      Hospital in Oxford, UK. INTERVENTION: Subjects were measured using a Kin-Com
      dynamometer to assess maximum isometric force and a leg extensor power rig to
      assess maximum single leg explosive power. RESULTS: Twenty-six patients (mean
      age: 72 years; SD: 8 years; range: 50-87 years) were included in the study
      following informed consent. A weak relationship was found between LEP, IQF and
      pain scores which reached the 5% significance level for the LEP measures only.
      The level of repeatability for both measures was found to be acceptable.
      CONCLUSION: Both LEP and IQF are recommended as repeatable measures for
      assessment of muscle function in patients with osteoarthitis of the knee.
      However, the LEP rig has the added advantage of being quicker, cheaper and
      simpler to use in the clinical setting.

PMID- 9619654
TI  - Quadriceps strength and timed motor performances in myotonic dystrophy, Charcot
      Marie-Tooth disease, and healthy subjects.
AB  - BACKGROUND AND PURPOSE: The leading hypothesis was that a relation exists between
      muscular strength and functional abilities. Therefore a study was undertaken to
      quantify such a relationship in a population of subjects with different muscular
      strengths. This population consisted of healthy subjects and subjects with slowly
      progressive neuromuscular disorders. METHODS: The study included 33 patients with
      myotonic dystrophy, 29 patients with Charcot-Marie-Tooth disease and 20 healthy
      subjects. Isokinetic and isometric knee torques were measured on an isokinetic
      dynamometer at various velocities. The following activities were timed:
      descending and ascending stairs, rising from a chair, rising from supine, walking
      at natural speed and walking at maximum speed. RESULTS: The population covered a
      wide range of the variables: whereas the healthy subjects performed best (i.e.
      had the highest knee torques and performed the activities most quickly), the
      myotonic dystrophy group included the subjects with the lowest knee torques. The
      natural logarithms (In) of isokinetic extension torque at the highest velocity
      (120 degrees/s) and those of the time taken to perform the described activities
      showed the highest levels of correlation. It was found that after correction for
      age and weight, 56% (walking at natural speed) to 73% (descending stairs) of the
      variance in the In of the time taken could be attributed to the variance in the
      In of the torques. CONCLUSION AND DISCUSSION: A strong relation between
      quadriceps strength and timed motor performances were demonstrated. The impact of
      strength reduction on time taken was most obvious in subjects with considerably
      decreased strength. Therefore, it is feasible to try to influence muscle strength
      in patients with relevant strength reduction in order to achieve better
      functional ability.

PMID- 9619655
TI  - An evaluation of current risk assessment scales for decubitus ulcer in general
      inpatients and wheelchair users.
AB  - OBJECTIVES: To study the components of two risk assessment scales for decubitus
      ulcer risk, Waterlow and Braden, and of the Chailey score for the same purpose.
      DESIGN: Experimental study of patients at risk of developing decubitus ulcers.
      SETTING: The West Midlands and Yorkshire. SUBJECTS: One hundred and fifty
      wheelchair users from the West Midlands and 9022 patients from a District General
      Hospital in York, the latter consisting of all admissions to the hospital in a
      four-month period. INTERVENTIONS: Braden, Chailey scores (wheelchair users) and
      Waterlow scores (all subjects) measured. MAIN OUTCOME MEASURES: Development of a
      pressure sore, receiver operating characteristic (ROC) curves. RESULTS: Waterlow
      outperformed Braden for classification of wheelchair patients with respect to
      decubitus ulcer. The Chailey score performed randomly in this group. The
      sensitivity and specificity as seen in ROC curves was different for Waterlow
      scores for wheelchair users and general patients, the latter being much better
      classified. Only three items out of 11 in the Waterlow score appeared to have any
      classification ability in the wheelchair group. CONCLUSIONS: Risk indicators used
      for general patients are probably poorly suited for wheelchair users. There is a
      need for large-scale predictive studies of wheelchair users and other groups to
      allow regression analysis of the subscales of risk indicators. From the
      provisional data of this study it appears that splitting patients by gender and
      into full- and part-time wheelchair users classifies almost as well the much more
      complicated risk assessment tools currently available.

PMID- 9619656
TI  - Clinical experience of rehabilitation therapists with chronic diseases: a
      quantitative approach.
AB  - OBJECTIVES: To provide an overview of the numbers of patients with selected
      chronic diseases treated by rehabilitation therapists (physical therapists,
      occupational therapists, exercise therapists and podiatrists). The study was
      performed to get quantitative information on the degree to which rehabilitation
      therapists are experienced in the treatment of chronically ill patients. METHODS:
      Secondary analyses were performed on several databases containing representative
      data on patients treated by rehabilitation therapists. Rates per 1000 patients in
      the populations of these rehabilitation therapists and 90% confidence intervals
      were computed for patients with the following diagnoses: ischaemic heart
      diseases, stroke, rheumatoid arthritis, osteoarthritis, osteoporosis, multiple
      sclerosis, Parkinson's disease, epilepsy, headache syndromes, COPD/asthma,
      diabetes mellitus and chronic back pain (the size of the latter group could only
      be assessed in physical therapy in primary care). RESULTS: The largest group of
      chronically ill patients treated by physical therapists in primary care are
      patients with chronic back pain (82 per 1000). Stroke patients are the most
      common chronically ill patients treated by physical therapists in institutional
      care (157 per 1000) and by occupational therapists in institutional (358 per
      1000) and noninstitutional care (246 per 1000). These therapists also see a
      variety of other chronically ill patients. Exercise therapists and podiatrists
      treat less patients with the selected chronic diseases.

PMID- 9619657
TI  - A study of the factors which influence the length of hospital stay of stroke
      patients.
AB  - OBJECTIVE: To examine the factors which influence the length of hospitalization
      of stroke patients. DESIGN: Analysis of the relative importance of 10 preselected
      variables on the length of hospital stay of all patients admitted with a clinical
      diagnosis of stroke. The data were collected prospectively. SETTING: Two teaching
      hospitals serving the city of Southampton and southwest Hampshire, England
      (approximate population 450000). SUBJECTS: Forty-six consecutive stroke patients.
      RESULTS: Data were complete on 38 patients. The mean and (median) length of
      hospital stay was 74.9 (80.5) days for men and 74.7 (73.5) for women. The mean
      age of women in the study sample was higher than that of men (73.2 vs 71.6).
      Patients who were less than 70 years of age stayed shorter periods in hospital
      than older subjects. Other factors associated with shorter hospitalization were a
      stroke type other than total anterior circulation infarct, a Barthel score of 12
      or more on admission or at the time of discharge and a frequency of consultants'
      ward rounds of more than one per week. A delay in the provision of equipment and
      home adaptations and waiting for placement in a private nursing home were the
      best predictors of long hospital stays of stroke patients. CONCLUSIONS: Early
      liaison of rehabilitation staff with Social Services in order to secure the quick
      provision of environmental aids and adaptations or placement in residential care
      of stroke patients with a poor prognosis for functional recovery would probably
      reduce the unnecessary hospitalization of these patients.

PMID- 9619658
TI  - Camptocormia: a case of possible paraneoplastic aetiology.
AB  - We present a patient with gradual development of camptocormia, three years before
      a non-Hodgkin's lymphoma was diagnosed. Lymphomas are known to produce
      neuromuscular symptoms through several indirect mechanisms. Recent studies regard
      camptocormia as a primary disease of the paravertebral muscles. To our knowledge
      this is the first report associating camptocormia with malignancy. The
      possibility of a paraneoplastic syndrome is discussed.

PMID- 9619659
TI  - A celebration of the "impossible".

PMID- 9619660
TI  - A contra-angle saw blade for intraoral vertical osteotomy.

PMID- 9619661
TI  - Antibodies in oral lichen planus.

PMID- 9619662
TI  - Osteocartilaginous exostosis of the mandibular condyle misdiagnosed as
      temporomandibular joint dysfunction.

PMID- 9619663
TI  - Cervicofacial actinomycosis.

PMID- 9619664
TI  - Dental implant installation without antibiotic prophylaxis.
AB  - The objective of this study was to retrospectively compare the outcomes of dental
      implant treatment with and without antibiotic prophylaxis. Two groups of patients
      with edentulous or partially edentulous maxillas or mandibles (or both) were
      treated with dental implants. One group, consisting of 147 patients (790
      implants), was given prophylaxis with oral phenoxymethylpenicillin; 1 g of
      antibiotic was administered 1 hour preoperatively, and 1 g was administered every
      8 hours for 10 days postoperatively. The other group, consisting of 132 patients
      (664 implants) was not given any antibiotics preoperatively or postoperatively.
      There were no significant differences with respect to early and late
      postoperative infections or with respect to implant survival between the two
      groups. It appears that antibiotic prophylaxis for routine dental implant surgery
      offers no advantage for the patient.

PMID- 9619665
TI  - Preliminary evaluation of hydroxyapatite cement as an augmentation device in the
      edentulous atrophic canine mandible.
AB  - OBJECTIVE: The purpose of this study was to answer the following two questions:
      (1) Can hydroxyapatite cement in combination with demineralized freeze dried bone
      feasibly augment the dimension of an atrophic edentulous canine mandible? (2)
      What is the histologic fate of an augmentation graft composed of hydroxyapatite
      cement and demineralized freeze dried bone placed on the surface of an atrophic
      edentulous canine mandible? STUDY DESIGN: Each of four mixed-breed canines
      (weighing 50 to 60 pounds) underwent bilateral mandibular dental extraction
      (canine to second molar) and radical alveolectomy. After 4 months of healing, a
      bilateral subperiosteal mandibular augmentation graft was put into place, with
      hydroxyapatite cement/demineralized freeze dried bone on the surface of one
      hemimandible and porous granular hydroxyapatite and demineralized freeze dried
      bone on the surface of the other hemimandible. The animals were killed after
      functioning on a soft diet for 9 months, and the grafted hemimandibles were
      harvested. RESULTS: Both hydroxyapatite cement and granular hydroxyapatite grafts
      appeared to augment the edentulous atrophic canine mandible. On histologic exam,
      the hydroxyapatite cement grafts showed osteoconduction and subperiosteal and
      endosteal osteonal bone formation, whereas the granular hydroxyapatite grafts
      showed only osteoconduction. Neither graft material showed chronic or acute
      inflammation. CONCLUSION: Hydroxyapatite cement can function feasibly as a
      mandibular augmentation device. The histologic fate of hydroxyapatite cement is
      different from that of granular hydroxyapatite. It has a fate comparable to
      autograft or allograft cortical bone grafts.

PMID- 9619666
TI  - Diamond fraise technique for dermal grafts in temporomandibular disk
      reconstruction.
AB  - Dermal grafts have been described for a variety of applications, including
      preprosthetic surgery, reconstructive surgery, and temporomandibular joint
      surgery. Several reports have described the procedural techniques for acquiring a
      dermal graft. The surgical technique for harvesting a dermal graft with the use
      of the dermabrading diamond fraise bur is described. The use of the diamond
      fraise bur offers many unique surgical advantages: it allows minimal damage to
      the dermal layer; the healing surface is smooth, cosmetic, homogenous, and devoid
      of scratches or debris; an adequate graft of uniform thickness is obtained; the
      technique allows access to a variety of donor sites; and minimal patient
      postoperative donor site morbidity. The use of this technique provides a simple,
      cosmetic approach to obtaining an adequate dermal graft for temporomandibular
      joint reconstructive procedures, while minimizing the potential complications
      associated with other commonly used techniques.

PMID- 9619667
TI  - Scintigraphic evaluation of healing response after heterograft usage for alveolar
      extraction cavity.
AB  - OBJECTIVE: Reconstruction of bone defects remains an important problem in oral
      and maxillofacial surgery. Restoration of defect sites with various grafting
      materials is a valuable approach to the solution of this problem. The aim of this
      study was to evaluate the effects of the use of heterografts on osteoblastic
      activity by means of a radionuclide technique. STUDY DESIGN: The postextraction
      alveolar cavities of impacted mandibular third molars on 22 patients were used as
      a healing model for this study. Granulated freeze-dried heterograft material of
      bovine origin was used on 11 patients; the other 11 patients constituted a
      control group. On each patient, three-phase bone scans were performed on
      postoperative days 7 and 28. RESULTS: Although dynamic and blood pool studies
      showed similar patterns with respect to the mean values of asymmetry ratios of
      operation sites to the contralateral sides for the 7th- and 28th-day scans,
      static-phase bone scans revealed that healing response through osteoinduction was
      more prominent in the study group than in the control group. A significant
      increase in the mean value of the ratio from the first scan to the second was
      observed on static images in the study group (first scan, 1.6 +/- 0.2; second
      scan, 2.0 +/- 0.5; p < 0.05). However, the same ratio failed to show any
      significant change in the control group (first scan, 1.5 +/- 0.2; second scan,
      1.5 +/- 0.3; p > 0.05). CONCLUSION: Static-phase bone scintigraphy showed that
      when freeze-dried heterograft material is used to fill alveolar extraction
      cavities, it stimulates osteoblastic activity, which in turn leads to
      acceleration of the healing process and helps to maintain the linearity of bony
      structure. Moreover, radionuclide study can be used to evaluate the viability of
      freeze-dried heterografts in the 4th postoperative week, at which time no
      additional increase in perfusion resulting from surgical trauma was found in our
      series.

PMID- 9619668
TI  - Synovial chondromatosis of the temporomandibular joint: the effect of interleukin
      1 on loose-body-derived cells.
AB  - OBJECTIVE: The purpose of this study was to investigate the effect of interleukin
      1 on cells from loose bodies of synovial chondromatosis of the temporomandibular
      joint. STUDY DESIGN: The cells were isolated from uncalcified loose bodies in a
      case of synovial chondromatosis of the temporomandibular joint and cultured in
      alpha-MEM medium containing 10% fetal bovine serum. The cells were treated with
      or without interleukin-1alpha and then stained with toluidine blue. Their
      conditioned media were analyzed with gelatin zymography to detect matrix
      degrading proteinase(s). RESULTS: The cells from loose bodies produced toluidine
      blue-stained matrix. When the cells were treated with 100 ng/ml of interleukin
      1alpha for 3 days, toluidine-blue-stained matrix was strikingly reduced. Gelatin
      zymography revealed that interleukin-1alpha-treated cells released 62-kDa
      gelatinase. CONCLUSIONS: Interleukin-1alpha may lead loose-body-derived cells to
      degrade the cartilaginous matrix of loose bodies in synovial chondromatosis of
      the temporomandibular joint.

PMID- 9619669
TI  - Preliminary investigation of the association of oral lichen planus and hepatitis
      C.
AB  - OBJECTIVE: The aim of this investigation was to determine if an association
      exists between hepatitis C virus and oral lichen planus. STUDY DESIGN: Three
      groups of subjects were selected: 505 patients with hepatitis C virus infection
      (group 1), 100 patients with oral lichen planus (group 2), and a randomly
      selected control group (age- and gender-matched) of 100 healthy subjects (group
      3). The prevalence of oral lichen planus was determined in groups 1 and 3, and
      the prevalence of hepatitis C virus infection was established in groups 2 and 3.
      RESULTS: The prevalence of oral lichen planus was 3.36% (n = 17) in group 1 and
      1% (n = 1) in the control group; the prevalence of hepatitis C virus infection
      was 23% (n = 23) in group 2, and 5% (n = 5) in the control group. No significant
      differences were observed in the incidence of oral lichen planus in group 1
      between those patients who received interferon and those who did not. The 17
      patients in group 1 who manifested oral lichen planus and hepatitis C virus
      infection simultaneously exhibited a marked tendency to have only reticular
      lesions (70.6%), with involvement of the buccal mucosa in 88.2% of these
      patients, the tongue in 29.4%, and the gingiva in 11.8%. Analyzing a randomized
      subgroup of 143 patients from group 1 (subgroup 1) that was matched by age and
      gender with groups 2 and 3, we found that the incidence of oral lichen planus in
      patients with hepatitis C virus infection (subgroup 1) was greater than in the
      control group (5.59% vs 1%), though this was not statistically significant (chi2
      = 0.119; p = 0.06). In contrast, group 2 exhibited a statistically significant
      higher incidence of hepatitis C virus infection (23%) than the controls (5%; chi2
      = 0.259, p = 0.0002). CONCLUSIONS: The prevalence of hepatitis C virus infection
      in patients with oral lichen planus was greater than in the control series. In
      our opinion this observation warrants the investigation of potential concomitant
      hepatitis C virus infection in patients with oral lichen planus.

PMID- 9619670
TI  - Autoimmune progesterone dermatitis and stomatitis.
AB  - Autoimmune progesterone dermatitis is a rare clinical condition associated with
      variable cutaneous and mucosal eruptions such as urticaria, erythema multiforme,
      and eczema. Exacerbation is influenced by hormonal changes of the menstrual
      cycle. The patient described in this report had recurrent cyclic lesions on the
      skin, oral mucosa, and lips that appeared just before regular menstruation and
      persisted until a few days after. During each cycle, the eruptions appeared at
      the previously affected sites, mimicking the clinical feature of a fixed drug
      eruption. This rare phenomenon is attributed to an autoimmune reaction to female
      sex hormones. The condition failed to respond to therapy with prednisone, but
      improved with the use of an antiestrogen drug, tamoxifen. This medication
      suppresses ovulation and the post-ovulation rise in endogenous progesterone
      levels.

PMID- 9619672
TI  - Solitary maxillary central incisor in the midline associated with systemic
      disorders.
AB  - A single maxillary central incisor in the midline is a rare developmental
      anomaly. The appearance of a single incisor in place of two teeth may occur as an
      isolated dental finding that can be related to fusion of two neighboring teeth or
      to agenesis of a tooth germ. However, the condition has also been reported to
      occur in association with autosomal dominant holoprosencephaly, growth
      retardation, and midline developmental defects. This article reports on other
      systemic defects that can be found in association with a single maxillary central
      incisor.

PMID- 9619671
TI  - Salivary electrophoresis in the diagnosis of Sjogren's syndrome.
AB  - OBJECTIVE: The purpose of this study was to investigate the potential use of
      salivary electrophoresis for the diagnosis of Sjogren's syndrome. METHODS:
      Salivary protein profiles of 43 patients and 39 healthy control subjects were
      compared on three different gel electrophoresis systems: sodium dodecylsulfate
      polyacrylamide gel electrophoresis, anionic polyacrylamide gel electrophoresis,
      and immobilized pH gradient gel electrophoresis (isoelectric point, 3.5-5.0).
      RESULTS: Most of the patients with Sjogren's syndrome exhibited an
      electrophoretic profile that was different from that of the healthy control
      subjects. Among the three gel electrophoresis systems examined, the immobilized
      pH gradient system appeared to be the most reliable for Sjogren's syndrome. Tests
      of accuracy revealed that the immobilized pH gradient system exhibits high
      specificity (97%), sensitivity (95%), positive predictive value (97%), and
      negative predictive value (95%) in the diagnosis of Sjogren's syndrome.
      CONCLUSIONS: Our results suggest that salivary electrophoresis is a potentially
      useful test for the diagnosis of Sjogren's syndrome.

PMID- 9619673
TI  - Concurrence of torus palatinus with palatal and buccal exostoses: case report and
      review of the literature.
AB  - Exostoses, also known as hyperostoses, are localized bony protuberances that
      arise from the cortical plate. These developmental anomalies, or hamartomas,
      frequently affect the skeletal jaw. Different types of exostoses have been
      described. Torus palatinus and torus mandibularis are two of the most common
      intraoral exostoses. Other types of exostoses, affecting the palatal aspect of
      the maxilla (palatal exostoses) or the buccal aspects of the jaws (buccal
      exostoses), are less commonly encountered. Concurrence of different forms of
      exostoses in the same individual is very rare. A 48-year-old woman manifesting
      excessive palatal exostoses, torus palatinus, and buccal exostoses is described.
      We present the clinical and histopathologic features and applied therapy and
      provide a comprehensive review of the current features of exostoses.

PMID- 9619674
TI  - Fluconazole-resistant Candida species in the oral flora of fluconazole-exposed
      HIV-positive patients.
AB  - The purpose of this study was to examine the effect of preceding fluconazole
      treatment on the oral mycologic flora and on the sensitivity of oral Candida
      albicans isolates to fluconazole. Saline oral rinses were collected from 89 HIV
      positive patients, of whom 48 had been exposed to fluconazole and 41 were
      fluconazole-naive. The rinses were cultured on Sabouraud's and Pagano Levin
      agars, and yeasts were identified by standard methods. Fluconazole sensitivity of
      C. albicans isolates was measured by disk diffusion assay. C. albicans was
      isolated from 69% of patients who had received fluconazole and from 93% of the
      patients who were fluconazole-naive (p < 0.05). Nine other species of yeasts were
      also isolated, most commonly C. glabrata. Five patients previously exposed to
      fluconazole harbored fluconazole-resistant C. albicans, whereas no resistance was
      detected among the patients who were fluconazole-naive (p < 0.01). Sixteen of the
      patients who were fluconazole-exposed carried yeasts other than C. albicans,
      compared with only five patients in the fluconazole-naive group (p < 0.01). All
      of the fluconazole-resistant strains were isolated from patients with low CD4
      counts (less than 100 cells/ml) and after lengthy fluconazole exposures.
      Nevertheless, patients in Charlotte, N.C., who had a greater mean fluconazole
      exposure time (10.25 +/- 1.41 months) than patients in Glasgow, UK, (0.65 +/-
      0.18 months; p < 0.005), did not develop significantly more in vitro resistance
      or species diversity. This study indicates that long-term fluconazole treatment
      can have significant effects on the yeast flora of the mouth, particularly in a
      patient with a CD4 count of less than 100 cells/ml.

PMID- 9619675
TI  - Parotid gland swelling in HIV diffuse infiltrative CD8 lymphocytosis syndrome.
AB  - HIV can affect salivary gland tissue. Parotid swellings have been observed in a
      subset of patients who are HIV-positive; the swellings are the result of a
      condition that has been termed diffuse infiltrative CD8 lymphocytosis syndrome.
      Initially the glandular enlargement results from a massive CD8 cell
      lymphoproliferation, but with time lymphoepithelial cysts become manifest. Two
      case reports are presented to illustrate this progression of diffuse infiltrative
      CD8 lymphocytosis.

PMID- 9619676
TI  - Molecular characterization of Warthin tumor.
AB  - OBJECTIVE: Warthin tumor of the salivary gland is composed of oncocytic
      epithelium with a prominent follicular lymphoid infiltrate. The purpose of this
      study was to characterize the clonality of this lymphoid component by means of
      polymerase chain reaction technology. STUDY DESIGN: DNA was isolated from
      paraffin-embedded tissue from 20 cases of typical Warthin tumor of the salivary
      gland and amplified by polymerase chain reaction to assess B- and T-cell
      clonality. RESULTS: No dominant clonal populations were identified in any tumor.
      However, minor clonal expansions of both B and T cells were detected in up to 50%
      of tumors (immunoglobulin H, 50%; T-cell antigen receptor beta, 10%; T-cell
      antigen receptor gamma, 5%). No tumors showed evidence of bcl-2 proto-oncogene
      translocation, whereas 95% contained detectable Epstein-Barr virus DNA.
      CONCLUSION: The B- and T-cell components of Warthin tumor are polyclonal with
      oligoclonal expansion of both T and B cells in some lesions.

PMID- 9619678
TI  - Angiomyolipomatous hamartoma of the tongue.
AB  - Extrarenal angiomyolipoma is a rare subtype of benign lipomatous tumor composed
      of adipose tissue, blood vessels, and smooth muscle. We report a 60-year-old
      woman who developed an angiomyolipomatous tumor of the tongue and discuss the
      differential diagnosis along with a review of the literature. The term
      angiomyolipomatous hamartoma is proposed for the present lesion to distinguish it
      from classic oral angiomyolipoma.

PMID- 9619677
TI  - Diameters of the main excretory ducts of the adult human submandibular and
      parotid gland: a histologic study.
AB  - In assessing new minimally invasive diagnostic techniques (duct endoscopy) and
      therapy (lithotripsy), it is of importance to know the true dimensions of the
      excretory ducts. Twenty-five ducts of the parotid gland and 20 ducts of the
      submandibular gland were examined histologically at different points of their
      anatomic course, and their in vivo diameters were evaluated with the use of a
      previously determined formalin-induced shrinking-factor. The mean diameter of
      Stensen's duct at four different points along its length ranged between 1.4 mm
      and 0.5 mm, with a maximum of 2.3 mm and a minimum of 0.1 mm, depending on the
      site. A narrowing at the middle of the duct was striking. In all preparations
      examined, the minimum width of the excretory duct was located at the ostium. In
      Wharton's duct the narrowest duct diameter was also identified at the ostium. The
      mean values for the duct diameters ranged between 1.5 mm and 0.5 mm. The largest
      duct diameter reached 2.2 mm; the smallest one, 0.2 mm. For diagnostic and
      therapeutic purposes, endoscopes, balloon catheters, and stone-extraction-baskets
      probably should, despite the extensibility of the duct, conform as much as
      possible to the physiologic duct widths. A diameter of 1.2 mm should be aimed at
      as an upper limit for these instruments. Our findings also suggest that, in the
      case of salivary stone lithotripsy, the best results will be achieved when the
      maximum size of stone fragments does not exceed 1.2 mm.

PMID- 9619679
TI  - The topography of root ends resected with fissure burs and refined with two types
      of finishing burs.
AB  - OBJECTIVES: This study compared the surface topography of roots resected with
      #57, Lindeman, and Multi-purpose burs. Further comparisons were made after
      refinements with either a multifluted carbide or an ultrafine diamond finishing
      bur. STUDY DESIGN: Three groups of single-rooted human teeth were resected with
      each resection bur, and resin replicas of the root ends were made. Root ends from
      each resection bur group were finished with either a multifluted carbide or an
      ultrafine diamond finishing bur, and the root ends were replicated. All replicas
      were evaluated at a magnification of x20 for smoothness and surface
      irregularities. Data analysis was done with the Wilcoxon signed rank test and the
      chi-square test at a significance level of p < 0.05. RESULTS: The Multi-purpose
      bur produced a smoother and more uniplanar surface than the #57 bur and caused
      less damage to the root than either the #57 or the Lindeman bur. The multifluted
      carbide finishing bur tended to improve the smoothness of the root end, while the
      ultrafine diamond tended to roughen the surface. CONCLUSIONS: The Multi-purpose
      bur produced the smoothest and most uniplanar resected root-end surface with the
      least root shattering. The multifluted carbide finishing bur produced a smoother
      surface than the ultrafine diamond bur.

PMID- 9619681
TI  - Quantitative assessment of temporomandibular joint disk status.
AB  - The purpose of this study was to quantify temporomandibular joint disk-slice
      information produced by magnetic resonance imaging by means of a stepwise
      discriminant analysis. One hundred ninety-four adolescents consented to magnetic
      resonance imaging evaluation of their temporomandibular joints. Sagittal magnetic
      resonance imaging slices of each joint were assigned to one of six subjective
      categories of disk position by an experienced maxillofacial radiologist.
      Standardized reference planes transferred to each magnetic resonance image from
      corresponding lateral cephalometric radiographics facilitated the measurement of
      disk length and disk displacement and the computation of ratio values of these
      measurements. Discriminant analysis revealed that all three quantitative
      variables were descriptive and discriminant for grouping slice data into pre
      established subjective categories. Cross-validation and misclassification error
      calculations showed a 69.3% agreement between subjective and discriminant
      classification. Therefore quantification of disk displacement can be used in
      place of subjective evaluation. In addition, discriminant analysis disclosed a
      reduction in disk length associated with increased severity of disk displacement.

PMID- 9619680
TI  - Cytotoxicity of four root canal sealers in permanent 3T3 cells and primary human
      periodontal ligament fibroblast cultures.
AB  - OBJECTIVES: The purposes of this study were to determine the cytocompatibility of
      four endodontic sealers and gutta-percha using various extracts and to compare
      the cellular injuries resulting from these materials in permanent 3T3 monolayers
      and primary human periodontal ligament fibroblasts. STUDY DESIGN: Set specimens
      from four sealers (AH26, Apexit, Sealapex, N2) as well as gutta-percha were
      eluted with cell culture medium for 24 hours, 5 days, 5 days, and 24 hours,
      respectively. Cytotoxic effects due to these extracts were evaluated by
      determining proliferation of permanent 3T3 cells and primary human periodontal
      ligament fibroblasts by means of the fluorochrome propidiumiodide. RESULTS: No
      statistically significant cellular alterations were induced by gutta-percha and
      Apexit, whereas various extracts of AH26 and Sealapex caused significant moderate
      or severe growth inhibition. Severe cellular damage was documented for all
      extracts of N2, which was statistically significantly different from the other
      materials in both cell lines (p < 0.05). CONCLUSIONS: Our results confirm that
      various root canal sealers constantly segregate substances after being exposed to
      an aqueous environment for extended periods, possibly causing moderate or severe
      cytotoxic reactions and possibly contributing to failure.

PMID- 9619682
TI  - Periodontitis detection efficacy of film and digital images.
AB  - OBJECTIVE: The objective of this study was to evaluate the accuracy of alveolar
      crestal bone detection in a comparison of unenhanced and enhanced Sidexis
      (Siemens Medical Systems, Inc., Bensheim, Germany) digital images with Ektaspeed
      Plus (Eastman Kodak, Rochester, N.Y.) films by means of receiver operating
      characteristic analysis. STUDY DESIGN: More than 100 proximal and furcal areas in
      the anterior and posterior areas of the mandible and maxilla of each of three
      tissue-equivalent human skull phantoms were imaged with film, direct digital
      images, and contrast- and brightness-enhanced digital images. Alveolar crest
      status was assessed by a consensus panel of three experts who used the Delphi
      method and evaluated information from all of the imaging modalities concurrently.
      Five observers assessed all images for the presence or absence of crestal bone
      loss using a five-point confidence scale. Receiver operating characteristic
      curves were generated, and calculated areas (Az) were analyzed by means of
      analysis of variance. RESULTS: The expert panel determined that of 106 crestal
      areas, 48 were disease free and 58 exhibited bone loss greater than 2 mm apical
      to the cemento-enamel junction. Analysis of variance of observer Az scores showed
      significant differences among readers (p < 0.001) and among readings (p = 0.027),
      but not among modalities (p = 0.435). Mean Az values for the different modalities
      were as follows: Sidexis, 0.70; enhanced Sidexis, 0.71; Ektaspeed Plus films,
      0.735. CONCLUSION: The Sidexis digital imaging system was not significantly
      different from Ektaspeed Plus film for crestal bone evaluation in this in vitro
      study.

PMID- 9619683
TI  - Mucoepidermoid carcinoma in the mandible: findings of panoramic radiography and
      computed tomography.
AB  - Six patients with mucoepidermoid carcinoma in the mandible were studied with both
      panoramic radiography and computed tomography. Lesion shape and margin were
      evaluated on panoramic radiography, and bony expansion and cortical plate
      destruction were evaluated on computed tomography. In addition, a possible
      correlation among radiographic findings, histologic findings, and prognosis was
      investigated. Lesions found on panoramic radiography were classified into three
      types; each type pertained to two of the six patients. The lesion types were as
      follows: cystic, characterized by a large, cystic radiolucent area; rarefying,
      characterized by rarefying changes of the trabeculae; and infiltrative,
      characterized by a central ill-defined area of bony destruction. The results show
      that computed tomography is useful in the identification of tumor extent, bony
      expansion, and cortical plate destruction resulting from tumors. None of the
      patients whose lesions were of the cystic or rarefying type showed evidence of
      disease after surgery. In contrast, both of the patients whose lesions were of
      the infiltrative type died of their tumors. Histologic findings of the cystic and
      rarefying types showed tumors that were well-differentiated or moderately well
      differentiated, whereas findings of the infiltrative type showed poorly
      differentiated tumors. Radiographic findings correlated with histologic findings
      and prognosis of mucoepidermoid carcinoma in the mandible in this limited series.

PMID- 9619684
TI  - Histopathologic and radiographic findings of the simple bone cyst.
AB  - OBJECTIVE: The purpose of this study is to examine the correlation between
      histopathologic and radiographic findings and to discuss the cause of the simple
      bone cyst. STUDY DESIGN: Histopathologically, we classified 53 simple bone cysts
      into two types. Type A has a connective tissue membrane and type B has a
      partially thickened wall with dysplastic bone formation. Radiographically, we
      evaluated the following: margin, radiolucency, or radiopacity, relationship with
      tooth apices, bucco-lingual bone expansion, and displacement of the mandibular
      canal. RESULTS: Bone expansion and radiopacity were closely related to
      histopathologic findings although there was no correlation between the
      histopathologic findings and radiographic margin, relationship with tooth apices,
      and displacement of mandibular canal. Local recurrence was more likely to be
      observed in patients diagnosed as having type B than type A lesions. CONCLUSIONS:
      Type A and type B bone cysts may have different causes. Cysts determined
      radiographically to be radiopaque, those diagnosed as type B histopathologically,
      and cysts that have been treated surgically should all be followed by
      radiographic examinations.

PMID- 9619685
TI  - Studies on the role of nicotinic acetylcholine receptors in the discriminative
      and aversive stimulus properties of ethanol in the rat.
AB  - The role of the nicotinic acetylcholine receptor (nAChR) in the discriminative
      and aversive stimulus effects of ethanol was studied in rats. In the operant drug
      discrimination procedure the rats were trained to discriminate between 1.0 g/kg
      ethanol and saline under the FR10 schedule of sweetened milk reinforcement.
      Neither the nAChR agonist, nicotine (0.1-0.6 mg/kg) nor the nAChR antagonist,
      mecamylamine (3.0-6.0 mg/kg) substituted for the ethanol stimulus. Moreover,
      mecamylamine (0.5-6.0 mg/kg) did not antagonise the ethanol stimulus. The cross
      familiarisation conditioned taste aversion procedure was used as an alternative
      method to study stimulus resemblance between ethanol and nicotine. Six daily
      injections of nicotine (0.6 mg/kg) significantly decreased a subsequent ethanol
      induced taste aversion conditioning. The aversive stimulus effects of ethanol
      were investigated with the conditioned taste aversion (CTA) paradigm.
      Mecamylamine (1.0-3.0 mg/kg) did not attenuate an ethanol-induced CTA. These
      results suggest that: (1) nAChRs are not primarily involved in the discriminative
      stimulus effects of ethanol when studied with the operant drug discrimination
      test; (2) nAChRs are not critically involved in the ethanol-induced CTA.

PMID- 9619686
TI  - The effect of clinical outcome on platelet G proteins of major depressed
      patients.
AB  - Platelet G protein subunits (G alpha i2, G alpha q and Gbeta) were measured in 15
      non-treated depressed patients (recurrent major depression) and 15 age- and sex
      matched healthy controls by using the Western immunoblot method. The depression
      severity was measured by the AMDP depression rating scale before start of
      treatment. The AMDP score ranged between 12 and 44. Patients were then treated
      with different antidepressant drugs (ATD) for 1 month, after which G protein and
      depression were reassessed. Results indicated that drug-free depressed patients
      displayed increased levels of G proteins subunits, in comparison to healthy
      controls. Antidepressant drug administration resulted in decrease of depression
      severity but only seven patients showed a net response to drugs (AMDP depression
      score less than 12). These drug-responding patients have also reduced G protein
      levels, while patients without significant improvement continued to display
      either the same levels of G proteins or higher, whatever the class of the drug
      administered. These results suggest that depression is associated to increase in
      G protein subunit levels and that the clinical outcome seemed to be the
      determining factor in further decrease occurring in G protein levels.

PMID- 9619687
TI  - Effects of risperidone and SCH 23390 on isolation-induced aggression in male
      mice.
AB  - In this study, the antiaggressive effects of risperidone and SCH 23390 have been
      explored. Using the paradigm of isolation-induced aggression, 150 albino male
      mice of the OF1 strain were allocated to control and experimental groups which
      received three doses of risperidone (0.01, 0.05 and 0.1 mg/kg) or two doses of
      SCH 23390 (0.05 and 0.1 mg/kg). Only the highest doses of risperidone decreased
      threat and attack behaviours but all doses significantly impaired motor
      behaviour. SCH 23390 decreased attack with the two doses used and also produced
      significant increases in immobility. Although both antipsychotics are
      antiaggressive, this action seems to be more specific in the case of risperidone.
      Finally, both drugs failed to affect animals with short attack latency, being
      antiaggressive only in subjects with long attack latency, which suggests that
      these two types of animals are different in their dopamine and serotonin
      neurotransmission.

PMID- 9619688
TI  - Chronic verapamil modifies striatal and frontal cortex dopamine levels.
AB  - In an attempt to elucidate if a change in dopamine (DA) levels was involved in
      the antimanic action of verapamil reported in various clinical studies, monoamine
      concentrations in three brain regions (striatum, frontal cortex and hippocampus)
      obtained from verapamil-treated rats (10 mg/kg i.p. per day for 21 days) were
      quantified by HPLC coupled to electrochemical detection, and compared with
      monoamine concentrations in haloperidol-treated animals (5 mg/kg i.p. per day for
      21 days). We have found that verapamil and haloperidol, when injected for 3 weeks
      to rats sacrificed 2 h after the last injection, decreased the striatal DA
      concentration to a similar extent. This decrease was not observed in short-term
      (one injection 2 h before sacrifice) verapamil- or haloperidol-treated rats.
      Moreover, after such a single injection of verapamil the striatal DA
      concentration was even increased. The striatal concentration of 3,4
      dihydroxyphenylacetic acid (DOPAC) was increased about two-fold by haloperidol,
      but not by verapamil. This haloperidol-induced increase in striatal DOPAC was
      similar after one injection and after 21 days of haloperidol administration.
      Neither verapamil nor haloperidol modified the concentrations of homovanillic
      acid (HVA) or 3-methoxytyramine (3-MT) in the striatum. In the frontal cortex,
      chronic verapamil increased the concentrations of DA two-fold, and chronic
      haloperidol increased the concentration of DOPAC two-fold. The other DA
      metabolites, namely HVA and 3-MT were not significantly changed. The
      concentration of serotonin (5-HT) and its main metabolite, 5-hydroxyindoleacetic
      acid (5-HIAA), in control, verapamil- and haloperidol-treated rats were similar
      in the three brain regions studied. We conclude that DA autoreceptors are
      implicated in verapamil's effects on frontal cortex and striatum DA levels; and
      that the presumed antimanic action exerted by verapamil is due to its long-term
      effect on these receptors.

PMID- 9619689
TI  - Effects of the D3 preferring dopamine agonist pramipexole on sleep and waking,
      locomotor activity and striatal dopamine release in rats.
AB  - Quantitation of 2 h sessions after administration of the D3 preferring dopamine
      (DA) agonist pramipexole (10-500 microg/kg) showed dose-related effects on
      wakefulness (W), slow wave sleep (SWS) and REM sleep in rats. The 30 microg/kg
      dose of the DA agonist increased SWS and REM sleep and reduced W during the first
      recording hour, while the 500 microg/kg dose augmented W. On the other hand, W
      was increased while SWS and REMS were decreased after the 500 microg/kg dose
      during the second recording hour. The mixed D2- and D3 receptor antagonist YM
      09151-2 (30-500 microg/kg), which per se affected sleep variables prevented the
      increase of REMS induced by pramipexole. Furthermore, the highest doses (500-1000
      microg/kg) of the DA antagonist effectively antagonized the increase of W and
      reduction of SWS induced by the 500 microg/kg dose of the DA agonist. Pramipexole
      (30-100 microg/kg) induced a decrease of locomotor activity during the 2 h
      recording period. In addition, the 500 microg/kg dose gave rise to an initial
      reduction of motor behavior which was reverted 2 h later. Pramipexole (30 and 500
      microg/kg) did not significantly affect striatal DA release during the first two
      hours following drug administration, as measured by microdialysis. It is
      tentatively suggested that D3 receptor could be involved in the pramipexole
      induced increase of sleep and reduction of locomotor activity. On the other hand,
      the increase of W and of motor behavior after relatively high doses could be
      related to activation of postsynaptic D2 receptor.

PMID- 9619690
TI  - Pulse loading versus gradual dosing of intravenous clomipramine in obsessive
      compulsive disorder.
AB  - OBJECTIVE: We compared gradually increased to pulse loaded doses of open-label,
      intravenous clomipramine (CMI) in patients with obsessive-compulsive disorder
      (OCD). METHOD: We treated adult outpatients with DSM-III-R OCD, who had no prior
      exposure to effective treatments. Pulse loading patients received 150 mg on day
      1; 150 mg or 200 mg on day 2. Gradual dosing patients received 25 mg per day
      increased to 200 mg per day over 2 weeks and then continued for a mean of 43 days
      (n=40). After i.v. dosing, all patients received oral CMI; the total treatment
      period was 6 months. RESULTS: Pulse loading completers (n=7) had a rapid,
      dramatic response (mean Y-BOCS score decrease of 32% five days after pulse
      loading). At this point (day 7), completers in the gradual intravenous group
      (n=20) exhibited no mean change in Y-BOCS score. The pulse loading group reached
      both a 25% or greater and a 50% or greater decrease in Y-BOCS score statistically
      and clinically significantly faster than the gradual group. CONCLUSIONS: Pulse
      loaded intravenous CMI for the treatment of OCD deserves further study.

PMID- 9619691
TI  - Chirality of reduced haloperidol in humans.
AB  - In vitro, cytosolic human ketone reductases catalyse the stereospecific (i.e.
      >99%) formation of S(-) reduced haloperidol (RHP) from haloperidol (HP). Whether
      this situation is reflected in patients taking the drug is unknown. In this study
      in nine patients taking HP, only 73.2+/-18.2% of the RHP excreted in urine was
      the S(-) enantiomer. Thus, enzymes other than cytosolic ketone reductases must be
      responsible for the formation of the minor enantiomer.

PMID- 9619692
TI  - Effects of serotonin and metergoline on 125[I]-iodocyanopindolol binding
      parameters to beta-adrenergic receptors in rat brain.
AB  - Most ligands which have been employed to investigate the regulation of beta
      adrenergic receptors (betaAR) under pathophysiological conditions and in response
      to pharmacological manipulations have also been shown to have affinity for 5-HT1B
      receptors. We examined the effects of serotonin and metergoline (10 microM) on
      125I-iodocyanopindolol (ICYP, 5-100 pM) binding to betaAR in rat frontal cortex
      and hippocampus membranes. In both brain regions, the presence of either
      serotonin or metergoline significantly lowered iodocyanopindolol dissociation
      constant (Kd) and maximum binding capacity (Bmax). Isoproterenol displacement
      curves showed that the decrease in receptor density was primarily due to a
      significant decrease in the receptors in the low-conformational state. Thus, a
      significant fraction of the apparent ICYP binding to betaAR in the low
      conformational state was due to binding to 5-HT1B receptors. Neither serotonin
      nor metergoline had an effect on the agonist isoproterenol dissociation constant
      from betaAR in either conformational state.

PMID- 9619693
TI  - The role of N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission in
      the pathophysiology and therapeutics of psychiatric syndromes.
AB  - The study of excitatory amino acids (EAAs) has recently resulted in new and
      fundamental concepts in neuroscience. This progress has led to a growing
      awareness of the crucial role that brain EAAs systems play in a variety of
      physiological and pathological processes. The N-methyl-D-aspartate (NMDA)
      receptor, presently the most well understood subtype of EAAs receptors, has been
      implicated in crucial physiological processes such as synaptogenesis, learning
      and memory. Dysfunctions of NMDA receptors seem to play a crucial role in the
      neurobiology of disorders such as Parkinson's disease, Alzheimer's disease,
      epilepsy and ischemic stroke. This paper is a review of emerging data indicating
      that alterations of NMDA receptor function may be pivotal to the pathophysiology
      of four common psychiatric syndromes: schizophrenia, major depression,
      posttraumatic stress disorder, and alcoholism. Special emphasis is placed on the
      current state of development of pharmacological strategies aiming at the
      modulation of NMDA receptor-mediated neurotransmission in these disorders.

PMID- 9619694
TI  - Cholecystokinin in CSF from depressed patients: possible relations to severity of
      depression and suicidal behaviour.
AB  - Levels of cholecystokinin (CCK) peptides were measured in the CSF from 105
      patients suffering from major depressive disorders admitted to a research
      psychiatric ward for diagnostic evaluation, by a radioimmunoassay method using
      two different antibodies. Relations between CCK levels and parameters of
      depression, anxiety, and suicidal behaviour were investigated. Significant
      inverse correlations were found between CCK levels and certain depression and
      anxiety parameters. Patients who had made one or more suicide attempts tended to
      have higher CSF CCK levels than those who had not. No correlations were found
      between CSF CCK and 5-HIAA or HVA, or with plasma cortisol.

PMID- 9619695
TI  - Experience with diffusion-weighted imaging in an acute stroke unit.
AB  - We performed diffusion-weighted MRI (DWI) on a standard 1.5-tesla MRI scanner
      using a high-speed stimulated echo pulse sequence (turboSTEAM) in 9 stroke
      patients and 9 control subjects to investigate whether this technique can be used
      clinically to assist in ischaemic stroke diagnosis within the time frame for
      potential therapy. Stroke patients underwent DWI between 3.75 h and 3 days after
      stroke onset. Three patients were studied on more than one occasion. DWI was
      normal in the 9 controls. Seven of 9 stroke patients showed areas of increased
      signal on DWI. DWI detected cerebral ischaemia 3.75 h after stroke onset when
      both CT and T2-weighted MRI were normal. In 6 DWI-positive patients studied at
      later times, increased signal on T2-weighted images was present at the same time.
      Two patients had normal CT, T2-weighted and DWI images; both made good
      neurological recoveries. For the routine assessment of stroke patients, DWI
      implemented on a standard MRI system can provide additional information of
      clinical value to that obtained with conventional pulse sequences. In particular
      it facilitates early detection of cerebral ischaemia during the first few hours
      after stroke.

PMID- 9619696
TI  - Poststroke atrial fibrillation bursts with sinus rhythm at stroke onset: what was
      the cause of stroke?
AB  - Intermittent atrial fibrillation may cause stroke, and acute stroke may lead to
      secondary bursts of atrial fibrillation. We studied with continuous ECG before,
      during and after stroke a patient with a history of intermittent atrial
      fibrillation. To our knowledge, this is the first case with continuous monitoring
      of atrial fibrillation bursts and their precise timing in the peristroke period.

PMID- 9619697
TI  - Symptomatic haemodynamically significant carotid occlusion treated by posterior
      circulation revascularization.
AB  - Haemodynamic cerebral ischaemic symptoms secondary to occlusive atheromatous
      disease of the internal carotid artery may resolve with revascularization. We
      describe a case of symptomatic internal carotid artery occlusion and ipsilateral
      subclavian stenosis with duplex and angiographically demonstrated vertebrobasilar
      steal and a patent ipsilateral posterior communicating artery with flow towards
      the steal. The patient suffered frequent ipsilateral middle cerebral artery
      territory transient ischaemic attacks and one minor stroke. Transcranial Doppler
      demonstrated markedly impaired ipsilateral carbon dioxide reactivity (13.8%,
      lower-limit normal range >32.6%). Percutaneous angioplasty to the subclavian
      artery stenosis resulted in resolution of symptoms and an improvement in
      reactivity to near the lower limit of the normal range (33.5%). This case
      demonstrates that normalization of vertebral artery steal by subclavian artery
      revascularization may benefit anterior circulation haemodynamic symptoms in the
      presence of a functioning posterior communicating artery. The measurement of
      middle cerebral artery reactivity using transcranial Doppler can identify such
      cases of haemodynamic impairment and monitor the effect of therapy.

PMID- 9619698
TI  - Vascular risk factors linked to multiple lacunar infarcts.
AB  - BACKGROUND: The pathogenesis of lacunar infarcts is still incompletely
      established. Data from the literature suggest that vascular risk factors differ
      among patients with multiple (MLI) and single lacunar infarcts (SLI). We
      reexamined this hypothesis using stricter inclusion criteria and a less selected
      study population. METHODS: We evaluated 136 patients consecutively admitted for
      first-ever minor stroke to a general hospital with the characteristics of a
      community hospital. Vascular risk factors were studied by univariate and
      multivariate statistical analyses among the following subgroups of patients,
      classified according to CT findings: (a) with lacunar infarct; (b) with
      nonlacunar infarct (NLI); (c) with SLI; (d) with MLI; (e) with single, either
      lacunar or nonlacunar, infarct. RESULTS: No significant difference was observed
      between patients with lacunar infarcts and patients with NLI. Compared to
      patients with SLI or NLI, patients with MLI had significantly more often a family
      history of hypertension, cardiomegaly on the chest radiograph and CT
      leukoaraiosis as well as a higher systolic and diastolic blood pressure on
      admission. Logistic regression analysis selected CT leukoaraiosis, Rx
      cardiomegaly and admission diastolic blood pressure as independent, significant
      predictors of MLI. CONCLUSION: In patients with first-ever minor stroke, the risk
      factor profile differs according to the evidence of SLI or MLI on the CT scan. In
      terms of risk factors, patients with SLI seem more similar to those with NLI than
      those with MLI. Based on the predicting effect of variables linked with type and
      severity of arterial hypertension, the CT appearance of MLI might express a more
      univocal and specific cerebrovascular pathology (hypertensive
      arteriolosclerosis).

PMID- 9619699
TI  - Pathophysiological assessment of nitric oxide (given as sodium nitroprusside) in
      acute ischaemic stroke.
AB  - Acute ischaemic stroke is characterised by reductions in local cerebral blood
      flow (CBF) and activation of circulating platelets and leucocytes. Nitric oxide
      is a vasodilator and can inhibit these circulating cells. The aim of this study
      was to assess the effect of nitric oxide on platelet function and regional CBF in
      patients with acute ischaemic stroke. Sodium nitroprusside (SNP), a spontaneous
      nitric oxide donor, was administered at a dose which caused a 10 mm Hg fall in
      mean arterial blood pressure (MABP) in a pathophysiological study to 22 patients
      with acute ischaemic stroke and 12 matched control subjects. Platelet function
      (whole blood aggregation and flow cytometry) was assessed before and during SNP
      administration. Changes in regional CBF were measured using single photon
      emission computerised tomography (SPECT) scanning. SNP significantly reduced
      platelet aggregation in both the patient and control subject groups. Equally, the
      expression of platelet adhesion molecules P-selectin (CD62) and glycoprotein (GP)
      GP IIIa (CD61) were significantly reduced in both groups. GP Ia (CDw49b)
      expression was significantly attenuated in the patient but not in the control
      group. Four patients underwent SPECT scanning and improvements in local CBF
      corresponding to the penumbral area of the clinical stroke site were seen in 3 of
      these patients. A total of 24 regions of asymmetrical perfusion were examined,
      pre-SNP (median (SQR)), 0.68 (0.14) vs. peri-SNP 0.78 (0.17), 2p = 0.065. SNP,
      given at a dose which reduced MABP by 10 mm Hg, significantly inhibited platelet
      aggregation and adhesion molecule expression. Improved regional CBF was seen in
      some patients. SNP is a candidate therapeutic agent for patients with acute
      ischaemic stroke and warrants further study.

PMID- 9619700
TI  - Incidence of space-occupying brain edema following systemic thrombolysis of acute
      supratentorial ischemia.
AB  - Whether 'malignant' brain edema following ischemic stroke is due to or aggravated
      by reperfusion and therefore more frequent after thrombolytic therapy of stroke
      is still under debate. From 3/96 to 1/97, we treated 51 patients with acute
      supratentorial stroke within 3 h after symptom onset with rt-PA following a
      protocol similar to the NINDS study. The results of thrombolytic therapy were
      evaluated by repeated clinical examination and computed tomography (CT) during
      the first week after ictus. The incidence of space-occupying brain edema
      following intravenous thrombolytic therapy of acute ischemic stroke was lower
      than the edema frequency after conventional treatment, but mortality from
      'malignant' edema was higher in the patients with thrombolysis. Thus, space
      occupying edema after acute ischemic stroke may be aggravated by thrombolytic
      treatment. Forced reperfusion of already irreversibly damaged tissue increases
      edema formation and enlarges developing infarcts with a deleterious increase of
      intracranial pressure.

PMID- 9619701
TI  - Multinational randomised controlled trial of lubeluzole in acute ischaemic
      stroke. European and Australian Lubeluzole Ischaemic Stroke Study Group.
AB  - BACKGROUND AND PURPOSE: Lubeluzole is a benzothiazole derivative that has shown
      neuroprotective properties in different experimental models. This multicentre,
      double-blind, placebo-controlled trial was conducted to assess the safety and
      efficacy of lubeluzole in patients with an acute ischaemic stroke. METHODS:
      Patients who presented with clinical signs and symptoms of acute cerebral
      hemispheric ischaemic stroke were randomised to intravenous therapy with placebo
      (n = 360) or lubeluzole 7.5 mg over 1 h followed by 10 mg/day for up to 5 days (n
      = 365). Treatment was initiated within 6 h of symptom onset. Mortality at 12
      weeks was the primary end point. Secondary end points included neurological
      status (European Stroke Scale), functional outcome (Barthel Index), and
      disability level (Rankin Scale). The primary and secondary end points were all
      analysed using the protocol-defined Cochran-Mantel-Haenszel's general association
      test. An additional analysis, the logistic regression approach, that included
      risk factors of age, baseline stroke severity and their interactions with
      treatment, was used to analyze outcome measures at 3 months. RESULTS: In the
      total ischaemic stroke population, the overall mortality rate at 3 months was
      similar for lubeluzole (21.0%) and placebo (21.4%). The logistic regression model
      confirmed the effect of age on mortality risk, but showed that this was
      independent of treatment. Treatment benefit was related to stroke severity, as
      determined by the Clinical Global Impression rating, that is a pronounced
      clinically significant reduction in mortality was noted in the lubeluzole-treated
      patients for whom stroke severity was mild to moderate, but not in those for whom
      it was severe. This was found on the basis of a post hoc analysis not specified
      in the hypothesis. Lubeluzole did not increase morbidity among stroke survivors,
      as measured by the European Stroke Scale, Barthel Index and Rankin Scale. No
      safety concerns were seen with lubeluzole treatment. CONCLUSIONS: In the overall
      study population, treatment with intravenous lubeluzole within 6 h of the onset
      of ischaemic stroke did not affect mortality or clinical outcome. Among patients
      with mild to moderate ischaemic stroke, lubeluzole decreased mortality without
      increasing morbidity.

PMID- 9619702
TI  - Warfarin, aspirin and microembolic signals in the acute phase of stroke in a
      patient with mechanical heart valves.
AB  - We report the case of a 54-year-old woman, with atrial fibrillation and
      mechanical heart valves, who suffered a left-hemispheric stroke while she was
      under warfarin. Daily bilateral simultaneous transcranial Doppler monitoring of
      the middle cerebral arteries showed the presence of microembolic signals (MES),
      whose number remained unchanged after adding aspirin 100 mg daily. We conclude
      that anticoagulant plus antiplatelet therapy does not influence the number of MES
      in the acute phase of stroke in patients with prosthetic heart valves, suggesting
      the gaseous origin of MES in these patients.

PMID- 9619703
TI  - A new type of extracranial/intracranial bypass for recurrent haemodynamic
      transient ischaemic attacks.
AB  - Since the completion of the international extracranial/intracranial (EC/IC)
      bypass study in 1985, no treatment of proven value has become available for
      patients with symptomatic carotid artery occlusion other than treatment with
      antithrombotic medication. However, in this trial the causal factors of cerebral
      ischaemia were not part of the inclusion criteria and also patients with single
      episodes only were included. We report successful Excimer laser-assisted high
      flow EC/IC bypass surgery in a patient with frequent transient ischaemic attacks
      associated with a low flow state of the cerebral circulation. In the 1.5 years
      after the operation the patient has never again experienced any symptoms of
      cerebral ischaemia. In addition there was improvement in cerebral blood flow,
      measured by magnetic resonance spectroscopy and hexamethylpropyleneamine oxime
      single photon emission computed tomography. Certain patients with occlusion of
      the internal carotid artery may benefit from EC/IC bypass surgery, in particular
      the Excimer laser-assisted high-flow bypass, that is, if recurrent (transient)
      ischaemic attacks are associated with compromised cerebral perfusion.

PMID- 9619704
TI  - An open study of clomethiazole in patients with acute cerebral infarction.

PMID- 9619705
TI  - Trends of colorectal cancer incidence and prevalence in Italian regions.
AB  - Incidence and prevalence of tumors of colon and rectum, estimated from mortality
      and survival data, are presented for Italian regions and for the period 1970
      1990. Projected rates to the year 2000 are also given. Age-standardized incidence
      rates have increased during the considered period. The increase has been higher
      for southern regions, which had, during the 70's, the lowest incidence and
      mortality levels. Geographic heterogeneity of colorectal cancer occurrence across
      Italian regions is therefore decreasing. The phenomenon parallels a tendency
      towards the homogenization of dietary habits observed in the Italian population.
      Estimated incidence levels increased less for the younger generation and appear
      stable for people born after 1940. More than 150,000 prevalent cases were
      estimated by the year 1990. The number is likely to increase owing to the
      simultaneous increasing tendency in incidence and survival rates.

PMID- 9619706
TI  - Synchronous and metachronous diagnosis of multiple primary cancers.
AB  - AIMS: In the time period near to the diagnosis of a new cancer, other tumors
      (synchronous cancers), especially slow-growing tumors, may be detected because
      several diagnostic examinations are performed. The frequency of synchronous in
      comparison with metachronous carcinomas has been evaluated in a population-based
      series of multiple primary cancers. METHODS: The case series of multiple primary
      cancers of the Tuscany Tumor Registry, incident during the period 1985-1991 was
      analyzed. For each site of a second independent tumor, the proportions of
      synchronous (diagnosed within 2 months of the first primary) and metachronous
      cancers were compared with the mean distribution (all sites except the specific
      one). RESULTS: During 1985-1991, 1095 patients had two independent tumors
      diagnosed; 216 were synchronous. The proportion of synchronous compared to
      metachronous cancers was significantly higher for bladder, prostate and renal
      cell carcinomas; it was significantly lower for lung cancer. When cancers
      following skin epitheliomas were evaluated, only the proportion of synchronous
      skin cancers was significantly increased. CONCLUSIONS: Silent slow-growing tumors
      are suspected to be more frequent in patients with prostate, bladder or renal
      cell carcinomas. In fact, they were most frequently diagnosed during
      ascertainment for another cancer. When few examinations were performed, as after
      the diagnosis of a skin epithelioma, no difference between metachronous and
      synchronous cancers was evident, except for skin.

PMID- 9619707
TI  - Identification, purification and characterization of a putative novel growth
      inhibitory and/or apoptotic protein from rat liver.
AB  - AIMS AND BACKGROUND: The existence of endogenous growth inhibitors was postulated
      in 1914 by Boveri. However, most regretfully, progress in the isolation,
      characterization and mechanisms of actions of endogenous growth-inhibitory
      proteins is scanty compared to the information available on growth-stimulatory
      proteins. Accordingly, the major purpose of the present study was to isolate and
      characterize an endogenous growth-inhibitory protein from normal rat liver so
      that its role during liver carcinogenesis could be evaluated. METHODS: For
      protein purification, a combination of alcohol precipitation, gel permeation
      chromatography and ion exchange chromatography techniques was utilized. For
      characterization and mechanisms, the methods utilized were DNA synthesis,
      immunoblotting, immunohistochemistry, protein sequencing, DNA-agarose
      electrophoresis and Hoechst staining. RESULTS: The purified protein inhibited the
      growth of several cell lines in culture as measured by the rate of DNA synthesis
      using 3H-thymidine. In SDS-PAGE stained by the silver staining method, the
      molecular weight of the polypeptide was found to be 14 kD. Polyclonal antiserum
      was raised against this 14 kD polypeptide in rabbit. Immunoblotting experiments
      showed that the antibody recognizes specifically the 14 kD polypeptide and
      immunolocalization studies showed that the polypeptide is predominantly a
      cytoplasmic protein. Addition of antibody and inhibitory polypeptide
      simultaneously to the cultures more or less abolished the inhibitory activity of
      the polypeptide. Sequencing of the N-terminal 17 amino acids of the growth
      inhibitory polypeptide showed Val-Leu-Leu-Ala-Glu-Ala-Glu-Thr-Ala-Ile-Val-Asn-Gly
      Leu-Asp-Lys-Ile. Comparing this sequence using a BLAST protein data base
      indicated that there was no significant homology between the sequence of the
      growth-inhibitory polypeptide and protein sequences deposited with the data bank,
      suggesting that this could be a novel growth-inhibitory polypeptide. The
      mechanisms of growth inhibition appeared to be apoptosis as determined by
      electrophoretic analysis of DNA fragmentation and staining of the cells with the
      dye Hoechst 33342. CONCLUSIONS: A growth-inhibitory protein of 14 kD can be
      isolated from normal rat liver. The physiologic role of the protein in liver
      appears to be either growth regulatory or apoptotic.

PMID- 9619708
TI  - Risk of endometrial cancer in breast cancer patients under long-term adjuvant
      treatment with tamoxifen.
AB  - AIMS: To evaluate the relative risk of endometrial cancer with respect to the
      expected underlying incidence in breast cancer patients undergoing long-term
      adjuvant tamoxifen therapy. METHODS: A total of 1010 postmenopausal breast cancer
      patients receiving adjuvant tamoxifen and with a first negative endometrial
      ultrasonography (cutoff for abnormal endometrial thickness >5 mm) were followed
      by annual transvaginal ultrasonography. Abnormal endometrial thickness prompted
      an outpatient endometrial biopsy or curettage under anesthesia in the case of
      cervical stenosis and increasing endometrial thickness. The standardized
      incidence ratio (SIR) with respect to underlying incidence was determined.
      RESULTS: A total of 1,010 eligible subjects who had been receiving tamoxifen for
      an average of 51 months were enrolled and followed for a total of 2,361 patient
      years between January 1993 and December 1996. Five cases of endometrial cancer
      were observed in the study period: 1 was detected at screening, and 4 were
      diagnosed for vaginal bleeding in the interval between screening examinations.
      SIR was 4.0 (95% confidence interval, 1.3-9.4) and increased to 4.8 (CI, 1.6
      10.5) when the single cancer detected at first screening was considered as
      incident. CONCLUSIONS: This study adds evidence to the hypothesis that long-term
      tamoxifen treatment may be responsible for a relevant increase in the risk of
      developing endometrial cancer. Surveillance based on endometrial ultrasonography
      was poorly sensitive, but the favorable stage at diagnosis of screen-detected or
      interval endometrial cancers does not support a more aggressive screening
      approach.

PMID- 9619709
TI  - Sentinel node biopsy and selective dissection for melanoma nodal metastases.
AB  - BACKGROUND: Early detection of nodal metastases still represents an important
      goal in the management of melanoma patients. A sentinel node is defined as the
      first colored node in the regional lymphatic basin following injection of blue
      dye in the site of the primary melanoma. Sentinel node biopsy may represent a
      feasible technique for early identification of occult disease. A therapeutic
      dissection is then performed only in patients with proven nodal disease, thus
      introducing the concept of selective dissection. METHODS: At the National Cancer
      Institute of Milan from February 1994 to October 1996, 74 patients with a
      melanoma of the trunk or limbs and without clinically detectable node metastases
      were submitted to sentinel node biopsy and eventual selective dissection.
      RESULTS: The sentinel node was identified in 67 patients (90%). Nodal metastases
      were detected in 11 patients (16%); 5 of these were identified by an
      intraoperative frozen section examination. In all but one case, only the sentinel
      node was affected at radical dissection. Incidence of positive sentinel nodes was
      correlated with depth of infiltration of the primary lesion. Mapped nodal basin
      failures were observed in 3 patients with negative sentinel node biopsy. All
      patients but one, presenting distant metastases, are alive at this writing and
      free of disease with a follow-up ranging from 2 to 34 months. CONCLUSIONS: Our
      study adds to accumulating evidence supporting the efficacy of sentinel node
      biopsy in detecting occult localizations and the potential of the technique to
      better select the group of patients that may benefit from nodal dissection.

PMID- 9619710
TI  - Image analysis in the RGB and HS colour planes for a computer-assisted diagnosis
      of cutaneous pigmented lesions.
AB  - AIMS AND BACKGROUND: A study was carried out to evaluate the effectiveness of
      image analysis performed by the two color representation models when a computer
      assisted diagnosis of melanoma is involved. METHODS: Color images of 40 skin
      pigmented lesions, which included 12 melanomas, were acquired by a standard color
      RGB video camera and stored in a PC for off-line processing. Image analysis was
      performed in the red green and blue color representation model and using hue and
      saturation color components. To describe shape and color characteristics of each
      lesion, including area, roundness and color variegation, 16 parameters were
      derived from red, green, blue, hue and saturation color planes and tested as
      possible variables useful to differentiate melanomas from benign nevi. RESULTS:
      The test gave a result of significance for six of the 16 derived image
      descriptors. The general trend of our data was in agreement with clinical
      observations according to which melanoma is usually darker, more variegated and
      less round than a benign nevus, whereas lesion dimension of melanomas and benign
      lesions was not significantly different. CONCLUSIONS: Our preliminary results
      suggested that image analysis performed on hue and saturation-derived and red
      green and blue-derived data could better discriminate melanoma from nevi than
      separately using the two color representation models.

PMID- 9619711
TI  - Analysis of interleukin-2/interleukin-2 receptor system in advanced non-small
      cell lung cancer.
AB  - AIMS AND BACKGROUND: The purpose of the study was to investigate the IL-2/IL-2
      receptor system in patients with advanced non-small-cell lung cancer (NSCLC).
      PATIENTS AND METHODS: Sera from 40 subjects and 80 patients with stage III and IV
      NSCLC were assayed for soluble interleukin-2 receptor (sIL-2R) and interleukin-2
      (IL-2) by the enzyme-linked immunosorbent assay. Circulating CD25+ cells were
      analyzed by flow cytoflorimetry. The data were related to clinical status by
      comparing the levels of sIL-2R and IL-2 at diagnosis and during the treatment.
      RESULTS: The mean sIL-2R concentrations of the NSCLC patients were significantly
      higher than the control population (P=0.0001); the patients with metastatic
      disease had significantly higher levels than those with locally advanced disease
      (P=0.02). No correlation was seen between circulating CD25+ cells and sIL-2R
      levels. Disease progression was associated with an increase in sIL-2R levels and
      a decline in IL-2; the sIL-2R/IL-2 ratio showed a gradual increase with tumor
      progression. CONCLUSIONS: Our study demonstrates in a large series of patients
      that in advanced NSCLC there is an imbalance of the IL-2/IL-2 receptor system.
      Furthermore, circulating sIL-2R levels and the sIL-2R/IL-2 ratio may be useful as
      markers of disease activity and treatment response, suggesting a potential
      prognostic value.

PMID- 9619712
TI  - Randomized comparison of goserelin acetate versus mitomycin C plus goserelin
      acetate in previously untreated prostate cancer patients with bone metastases.
AB  - In a prospective trial conducted by the Gruppo Onco Urologico Piemontese, newly
      diagnosed prostate cancer patients with bone metastases were randomized to
      receive goserelin (3.6 mg subcutaneously every 4 weeks) or goserelin plus
      mitomycin at 14 mg/m2 i.v. every 6 weeks. Treatment was planned to be continued
      until progression. The study was interrupted because of inadequate accrual rate
      when 63 patients had been recruited. A long-term follow-up (median, 47 months),
      performed to counterbalance the limited number of patients included, revealed no
      difference in time to progression and overall survival between the study
      treatments. However, 56.5% of assessable patients allocated to the chemotherapy
      arm presented a > or =90% reduction of prostate-specific antigen levels compared
      with 36.3% in the goserelin group, and previously elevated levels normalized in
      73.9% versus 45.4%. Non-progressing patients received 5-7 cycles of mitomycin C
      with acceptable toxicity, but the cytotoxic treatment was interrupted early in
      all cases within the first year due to cumulative myelotoxicity. In conclusion,
      the results, although inconclusive, fail to support a clear advantage in terms of
      cost/benefit of chemotherapy plus hormone therapy over hormone treatment alone in
      advanced prostate cancer with bone involvement.

PMID- 9619713
TI  - Clinical efficacy of the aromatase inhibitor anastrozole in relation to prolactin
      secretion in heavily pretreated metastatic breast cancer.
AB  - AIMS AND BACKGROUND: It is known that the aromatase inhibitors may act by
      decreasing estrogen levels. Moreover, it is known that estrogens may stimulate
      the release of prolactin (PRL), which is a growth factor for breast cancer. This
      phase II study was performed to evaluate the effects of the novel aromatase
      inhibitor anastrozole on PRL secretion in metastatic breast cancer and the
      possible influence of PRL pretreatment levels on the efficacy of therapy.
      METHODS: The study involved 14 pretreated metastatic breast cancer patients with
      a poor clinical status. Anastrozole was given orally once a day at 1 mg/day for
      at least 2 months. To evaluate PRL secretion, venous blood samples were collected
      before treatment and at 1-monthly intervals during treatment. RESULTS: The
      clinical response consisted of partial response (PR) in 2, stable disease (SD) in
      5 and progressive disease (PD) in the remaining 7 patients. Abnormally high
      pretreatment levels of PRL were seen in 5/14 (36%) patients. Progressing patients
      showed significantly higher pretreatment levels of PRL than those who achieved PR
      or SD. None of the patients with high PRL pretreatment levels showed a decline in
      PRL levels on treatment with anastrozole. CONCLUSIONS: This preliminary study
      suggests that anastrozole has no inhibitory effect on PRL secretion in metastatic
      breast cancer and that the evidence of abnormally elevated concentrations of PRL
      prior to therapy is generally associated with a lack of efficacy.

PMID- 9619714
TI  - Preliminary experience with high-dose cisplatin, reduced glutathione and natural
      interferon-alpha in dacarbazine-resistant malignant melanoma.
AB  - AIMS AND BACKGROUND: The incidence of malignant melanoma is rapidly increasing in
      many countries, and when this disease has reached advanced stages, standard
      therapies have little impact. Dacarbazine (DTIC) is the most effective
      chemotherapeutic agent with an overall response rate of 20-25%, but durable
      responses are uncommon. Interesting results with the use of cisplatin (CDDP) have
      been reported in DTIC-resistant melanoma. Moreover, malignant melanoma is an
      immunogenic tumor and a potential target for biological response modifier (BRM)
      therapies. The aim of the present study was to evaluate the efficacy and
      tolerability of a chemo-immunotherapeutic regimen including high-dose CDDP
      combined with glutathione (GSH) to limit platinum-related toxicity, and natura
      interferon-alpha (IFN-alpha) in patients with DTIC-resistant metastatic melanoma.
      METHODS: The treatment schedule included GSH 1,500 mg/m2 i.v. and CDDP 40 mg/m2
      i.v. for 4 consecutive days every 3 weeks, with a maximum of 6 courses, and IFN
      alpha 3 MIU i.m. 3 times a week, continuative for a maximum of 12 months.
      RESULTS: Twelve patients were enrolled in this phase II trial. Accrual was
      stopped due to treatment-related toxicity. Ten patients were evaluable for
      response; there were 2 partial responses, lasting 5+ and 9+ months, respectively,
      and 2 cases of stable disease, lasting 3+ and 8+ months. None of these patients
      completed the therapeutic program due to treatment-related side effects.
      CONCLUSIONS: This regimen seems to be only partially active in DTIC-resistant
      metastatic melanoma. Hematologic and non-hematologic (nausea and vomiting,
      peripheral neurotoxicity, and asthenia) side effects are significant and GSH is
      not effective in limiting CDDP-related neurotoxicity in pretreated patients.
      Therefore, there is no indication to employ this regimen as second-line treatment
      in metastatic melanoma and these disappointing results highlight the urgent need
      for new therapeutic approaches.

PMID- 9619715
TI  - Postoperative radiotherapy and surgery in stage I endometrial carcinoma: a 10
      year experience.
AB  - BACKGROUND: Data from the literature show that the incidence of pelvic
      recurrences in poor prognosis endometrial carcinoma is significantly reduced by
      combined surgery and radiotherapy compared to surgery alone. METHODS: In this
      paper we analyze the results of the combined treatment surgery plus adjuvant
      Irradiation in patients with endometrial carcinoma with regard to survival, site
      of progression, and toxicity. The surgical treatment consisted of total abdominal
      hysterectomy and bilateral salpingo-oophorectomy. Pelvic and para-aortic node
      dissection was performed. RESULTS: The overall 5-year survival was 88%. Three
      patients had local failure. Ten patients with local control of disease had
      distant metastases and 2 had local and distant recurrences. CONCLUSIONS: Our
      experience confirms the data of the literature. Postoperative irradiation is a
      safe and well tolerated treatment which can achieve good local control in high
      risk stage I endometrial carcinoma. The control of distant metastases remains an
      open issue.

PMID- 9619716
TI  - Follow-up protocols in orthopedic oncology.
AB  - Little has been written about the specific timing and elements Involved in the
      follow-up of orthopedic oncology patients. The experience with bone tumor
      treatment at the First Clinic of the Istituto Rizzoli started 30 years ago and
      more than 15,000 patients have been treated to date. The increment of limb
      salvage surgery is linked with the improvements in imaging and surgical skills
      and with the availability of new reconstructive techniques. For this purpose it
      is mandatory to carry out meticulous monitoring of the patients. A large number
      of patients are still followed up to evaluate the results in terms of oncological
      and functional status. Based on this experience we developed a time schedule to
      better respond to the need for adequate patient evaluation.

PMID- 9619717
TI  - Adult granulosa cell tumor of the ovary: a clinico pathologic study of 35 cases.
AB  - AIMS AND BACKGROUND: Adult granulosa cell tumor has a low malignant potential but
      requires an extensive follow-up of more than 5 years to accurately assess tumor
      activity. The aim of the present study was to evaluate the clinical
      characteristics, the treatment and the outcome of this rare ovarian tumor. STUDY
      DESIGN: A retrospective review of 35 cases treated at primary onset of disease
      during a 23-year period from 1971 to 1993. RESULTS: The disease-free survival
      rate for stages IA-B-C at 5 and 10 years was 90% and 84%, respectively; for
      stages III-IV the 5-year freedom from progression rate was 16%. CONCLUSIONS: The
      most important prognostic factor appears to be the extent of tumor involvement
      outside of the ovary.

PMID- 9619718
TI  - Meningiomas after radiotherapy for tinea capitis--still no history.
AB  - AIMS AND BACKGROUND: To review the clinical, radiological and histological
      findings of 19 patients with radiation-induced intracranial meningiomas treated
      at our neurosurgical department between 1981 and 1996. METHOD: The records of 18
      patients with intracranial meningiomas who underwent low-dose radiation for tinea
      capitis in childhood, and of one patient irradiated for pituitary adenoma, were
      analyzed in respect of the previously reported features of postradiation
      meningiomas. RESULTS: The mean age of the patients with low-dose radiation
      induced meningiomas was 58 years and the mean shortest onset latency was 48
      years. The male to female ratio was 1.1:1. Forty-seven percent of patients
      presented with mental changes and/or focal neurological signs, 21% with signs of
      increased intracranial pressure and 26% with seizures. Calvarial location of the
      meningiomas was found in 54% of patients and in one patient the tumor arose from
      the skull base. Multiple tumors were present in 15% of patients and 29% of the
      meningiomas displayed malignant features on histological examination. A
      significantly lower meningioma recurrence rate was found in our series compared
      to the recurrence rate in the reported series of postradiation meningiomas. Five
      patients had a history of a second neoplasm other than meningioma. CONCLUSION:
      Our series of low-dose radiation-induced meningiomas represents one of the
      largest of its kind in the English literature. The patients did not differ
      substantially in sex ratio, tumor localization, multiplicity and histological
      features from the previously reported postradiation meningioma patients, except
      for the significantly lower tumor recurrence rate. It would seem that over the
      next years we will be further witnessing the deleterious effects of low-dose
      radiation administered in childhood.

PMID- 9619719
TI  - Long-term survival in cerebral glioblastoma. Case report and critical review of
      the literature.
AB  - Glioblastoma multiforme is the most malignant tumor of the glial series. The
      average survival of patients with this tumor ranges from 6 to 12 months. The case
      of a patient who survived for more than 11 years after diagnosis of a temporal
      occipital glioblastoma which was treated with surgery, radiotherapy and
      chemotherapy is described. The authors deduce that among patients with
      glioblastoma multiforme (GM), those with a long disease-free interval after
      initial diagnosis who undergo multimodal therapy, including aggressive tumor
      removal, are the most likely long-term survivors (LS). Other factors which
      appeared to be related to longer survival were younger age and high Karnofsky
      scores.

PMID- 9619720
TI  - Primary plasmacytoma of the testis. A case report.
AB  - The authors describe a case of multiple myeloma that developed several
      extraskeletal localizations. They evaluated the relation between the onset of the
      testicular tumor and the following myeloma characteristics: tumor burden,
      clinical phase, response to therapy and prognostic significance. The patient
      presented a rapid and dramatic clinical evolution of the disease with extensive
      spread also to the soft tissues of the abdominal wall. Chemotherapy did not
      achieve any effect and the patient died due to progression of the myeloma.

PMID- 9619721
TI  - Gastrointestinal stromal tumors: a "benign" tumor with hepatic metastasis after
      11 years.
AB  - Gastrointestinal stromal tumors (GIST) constitue the largest category of primary
      non-epithelial neoplasms of the stomach and small bowel. They are characterized
      by a remarkable cellular variability and their malignant potential is sometimes
      difficult to predict. Very recent studies, using mitotic count and tumor size as
      the best determinants of biological behavior, divide GISTs into three groups:
      benign, borderline and malignant tumors. We report on a male patient who
      underwent a right hepatectomy for a large metastasis 11 years after the surgical
      treatment of an antral-pyloric gastric neoplasm, histologically defined as
      leiomyoblastoma and with clinical, morphological and immunohistochemical features
      of benignity (low mitotic count, tumor size < 5 cm, low cellular proliferation
      index). Histological and immunohistochemical analysis of the hepatic metastasis
      showed the cellular proliferation index (Ki-67) to be positive in 25% of
      neoplastic cells, as opposed to the primary gastric tumor in which Ki-67 was
      positive in only 5% of neoplastic cells. In conclusion, although modern
      immunohistochemical techniques are now available to obtain useful prognostic
      information, the malignant potential of GISTs is sometimes difficult to predict:
      neoplasms clinically and histologically defined as benign could metastasize a
      long time after oncologically correct surgical treatment. Therefore, benign GISTs
      also require consistent, long-term follow-up.

PMID- 9619722
TI  - Bone lesion in a patient with transplanted liver for a metastatic carcinoid. The
      role of somatostatin receptor scintigraphy.
AB  - A patient who had previously undergone ileal resection and liver transplantation
      for a gastroenteropancreatic (GEP) tumor was evaluated with somatostatin receptor
      scintigraphy (SRS) using 111In-DTPA-D-Phe1-pentetreotide. Eighteen months after
      surgery, during follow-up procedures, conventional imaging techniques
      (ultrasound, computed tomography, magnetic resonance imaging) only showed a
      relapse in the gastropancreatic lymph nodes, while SRS demonstrated skeletal
      spread. This case report emphasizes the clinical impact of SRS on the management
      of patients affected by neuroendocrine gastroenteropancreatic tumors.

PMID- 9619723
TI  - Metastatic adenocarcinoma presenting with central diabetes insipidus.
AB  - The case of a previously healthy 63-year-old female with metastatic
      adenocarcinoma to the hypothalamus presenting with central diabetes insipidus is
      presented. The patient was found to have metastatic disease isolated to her
      hypothalamus on brain magnetic resonance imaging as well as a water deprivation
      test consistent with central diabetes insipidus. The patient had a decrease in
      symptoms of polyuria and polydypsia as well as a decrease in urine volumes after
      treatment with intranasal vasopressin. Even though a rare occurrence, physicians
      should consider metastatic adenocarcinoma in patients with recent-onset polyuria
      and polydypsia.

PMID- 9619724
TI  - A phase II study of 5-aza-2'deoxycytidine (decitabine) in hormone independent
      metastatic (D2) prostate cancer.
AB  - AIMS AND BACKGROUND: Decitabine (5-aza-2'-deoxycytidine) is an S-phase-specific
      pyrimidine analog with hypomethylation properties. In laboratory models of
      prostate cancer (PC-3 and DU-145), decitabine induces cellular differentiation
      and enhanced expression of genes involved in tumor suppression, immunogenicity,
      and programmed cell death. METHODS: We conducted a phase II study of decitabine
      in 14 men with progressive, metastatic prostate cancer recurrent after total
      androgen blockade and flutamide withdrawal. Decitabine was administered at a dose
      of 75 mg/m2/dose i.v. as a 1 hour infusion every 8 hours for three doses. Cycles
      of therapy were repeated every 5 to 8 weeks to allow for resolution of toxicity.
      RESULTS: Two of 12 patients evaluable for response had stable disease with a time
      to progression of more than 10 weeks. This activity was seen in 2 of 3 African
      American patients. Toxicity was similar to previously reported experience. No
      significant changes in urinary concentrations of the angiogenic factor bFGF, a
      potential biomarker of tumor activity, were identified over time in 7 unselected
      patients with progressive disease. CONCLUSIONS: We conclude that decitabine is a
      well tolerated regimen with modest clinical activity against hormone-independent
      prostate cancer. Further investigations in patients of African-American origin
      may be warranted.

PMID- 9619725
TI  - Bone tissue in adrenal myelolipoma: a case report.
AB  - This paper describes a case of adrenal myelolipoma with an unusual
      characteristic: the presence of bone spicules. The lesion was associated with an
      accessory adrenal gland containing foci of myeloadiposis. The authors believe
      that myelolipoma and myeloadiposis are closely associated and are in fact the
      expression of a single process that is both focal (myeloadiposis) and diffuse
      (myelolipoma). The process consists of the differentiation of choristomatous
      primitive mesenchymal cells into hematopoietic tissue, adipose tissue and, in
      rare cases, bone tissue.

PMID- 9619726
TI  - Molecular cytogenetic analysis of B-cell chronic lymphocytic leukemia.
AB  - The genetic alterations underlying the pathogenesis of B-cell chronic lymphocytic
      leukemia (B-CLL) are difficult to assess. Cytogenetic studies are hindered by the
      low in vitro mitotic activity of the tumor cells and the limited resolution of
      chromosome banding. Molecular genetic analyses are hampered by nonclonal cells
      contained in the specimens and by the limited knowledge of candidate genes
      involved. As a complement to cytogenetic and molecular genetic techniques,
      fluorescence in situ hybridization (FISH) has proven powerful in the molecular
      cytogenetic analysis of B-CLL. FISH allows the detection of aberrations such as
      trisomies, deletions, and translocation breakpoints on the single cell level in
      dividing as well as non-dividing cells without the prerequisite of detailed
      physical maps or knowledge of involved genes. As detected by the interphase
      cytogenetic FISH approach, the most common chromosome abnormalities of B-CLL are
      deletions in band 13q14, followed by deletions in 11q22-q23, trisomy 12,
      deletions in 17p13, and deletions in 6q21. Abnormalities in 17p13 seem to involve
      the TP53 tumor suppressor gene, but as yet no candidate genes have been
      identified for the other frequent aberrations. Toward the identification of such
      genes by positional cloning, FISH can be applied for detailed aberration mapping
      at the molecular level. Furthermore, the accurate detection of chromosome
      aberrations in B-CLL by FISH provides a valid basis for the evaluation of their
      prognostic significance. Inactivation of TP53 in 17p13 and deletions in 11q22-q23
      have already been shown to be among the most important independent prognostic
      factors. Genetic abnormalities may eventually provide biological parameters,
      allowing a risk assessment for individual patients at the time of diagnosis of
      this clinically heterogeneous disease.

PMID- 9619727
TI  - Induction of telomerase activity in stimulated human lymphocytes precedes
      expression of topoisomerase II alpha.
AB  - Telomerase activity has been demonstrated in human immortal cell lines and in
      tumors, whereas it is generally absent from normal tissues, with the exception of
      germ cells. Low levels have also been detected in blood and skin cells. In this
      report we describe up-regulation of telomerase activity in normal human blood
      lymphocytes by mitogen stimulation. After 24 h of mitogen treatment a strong
      induction was detectable using the PCR-based telomeric repeat amplification
      protocol. The level of activity remained almost constant when the cultivation
      lasted 72 h. By contrast, topoisomerase II alpha was induced later with a maximum
      expression after 48-72 h. Our data show that telomerase can be induced in normal
      peripheral lymphocytes prior to expression of the S-phase typical protein
      topoisomerase II alpha indicating that telomere elongation might be initiated
      before DNA replication.

PMID- 9619728
TI  - Bcl-2 mRNA-targeted ribozymes: effects on programmed cell death in chronic
      myelogenous leukemia cell lines.
AB  - We used synthetic RNA transcripts to prove the cleavage capability of ribozymes
      targeted against bcl-2-related RNAs. No cleavage occurred when control
      oligonucliotides were used. To assess the functional role of the specific
      ribozymes in chronic myelogenous leukemia (CML) cell lines we cultured K562,
      BV173, and Daudi cells for 48 h after lipofection with 10 microM oligonucleotide.
      An increase in apoptotic cells, dependent on ribozyme specificity, was shown in
      BV173 cells. This finding was underlined by the typical morphological changes,
      but there is no correlation with regard to the level of bcl-2 protein expressed.
      Though bcl-2 appears to interfere with cell death in myeloid cells, bcl-2
      targeted ribozymes do not induce programmed cell death (PCD) by reducing bcl-2
      protein levels, but rather by a presently unknown mechanism.

PMID- 9619729
TI  - Defective natural killer cell activity of peripheral blood lymphocytes correlates
      with the degree of neutropenia in patients with chronic idiopathic neutropenia of
      adults.
AB  - Natural killer cell activity (Nka) of peripheral blood mononuclear cells (PBMCs)
      against K562 cell targets was assessed in 66 patients with chronic idiopathic
      neutropenia of adults (CINA) using the 16-h 51Cr-release assay. It was found that
      CINA patients exhibited significantly lower Nkr than normal subjects, which
      strongly correlated with the degree of neutropenia and the numbers of circulating
      neutrophils. Patients' NKa was increased by recombinant human interleukin-2 (rhIL
      2) or recombinant human interferon-alpha (rhIFN-alpha), but the values obtained
      did not reach the respective NKa values found in normals. However, percentages of
      cytokine-induced rises of NKa did not differ statistically between patients and
      normal subjects. No serum inhibitors of NKa were demonstrated in our patients.
      CINA patients had low numbers of circulating NK cells as defined by the
      expression of NK-cell-related surface markers CD16, CD56, and CD57. CD16+ and
      CD56+, but not CD57+, cells correlated with the values of baseline NKa. The
      numbers of all these cell subsets correlated with the degree of neutropenia and
      the numbers of circulating neutrophils. Using CD56+-enriched PBL suspensions, it
      was shown that patients' NK cells displayed normal tumor cell binding capacity
      and produced in vitro normal amounts of natural killer cytotoxic factor(s)
      against K562 cell targets upon activation with rhIFN-alpha. Finally, percentages
      of perforin-expressing and granzyme B-expressing CD16+ cells did not differ
      statistically between patients and normal controls. Based on all these
      observations, we concluded that CINA patients display low NKa probably because
      they have low numbers of circulating NK cells. No functional abnormalities of NK
      cells were demonstrated. The cause and the underlying mechanisms leading to NK
      cell depletion in these patients remain to be clarified.

PMID- 9619730
TI  - Hemoglobin F in myelodysplastic syndrome.
AB  - Reactivation of fetal hemoglobin synthesis in adulthood can be seen in
      hematological disorders affecting the erythropoietic system. The objective of the
      present study was to evaluate the incidence and prognostic significance of
      increased hemoglobin F in patients with myelodysplastic syndrome. Hemoglobin F
      concentrations and Ggamma/Ggamma + A gamma-globin chain ratios were determined in
      26 patients with primary myelodysplastic syndrome. Median age of the patients was
      65 years; all FAB subtypes were included. Increased hemoglobin F concentration of
      up to 20% of total hemoglobin (normal: below 2%) was seen in 16 patients; ten
      patients had normal values. There was a significant relation between hemoglobin F
      concentration and the course of disease, e.g., 12 of the 16 patients with
      elevated hemoglobin F survived at least 1 year after the examination, in contrast
      to only three of the ten patients with normal hemoglobin F (p < 0.025). All of
      six patients with hemoglobin F above 5% survived at least 1 year. There was no
      significant difference in the hemoglobin F concentration between patients with
      and without cytogenetic anomalies. The Ggamma/Ggamma + A gamma-globin chain ratio
      was slightly elevated in all patients, with a weak correlation to the degree of
      hemoglobin F elevation. The values were not of additional prognostic
      significance. The data of the present study suggest that the hemoglobin F
      concentration may be a prognostic parameter in myelodysplastic syndrome;
      increased hemoglobin F concentration may indicate a better prognosis.

PMID- 9619731
TI  - Comparison of karyotype analysis and RT-PCR for AML1/ETO in 204 unselected
      patients with AML.
AB  - The chromosomal translocation t(8;21) (q22;q22) is often associated with acute
      myeloid leukemia with maturation (AML-M2) and can be detected by a reverse
      transcription-polymerase chain reaction (RT-PCR) for the AML1/ETO fusion mRNA. We
      investigated the prevalence of t(8;21) and AML1/ETO in 204 unselected patients
      with AML and compared the results of cytogenetic analysis with these of RT-PCR.
      Fifteen of 204 AML patients (7.4%) showed a t(8;21) in karyotype analysis. In 17
      of 204 patients (8.3%) AML1/ETO was detected by RT-PCR. All patients who had a
      t(8;21) in conventional karyotyping also showed the gene rearrangement in
      molecular analysis, including one patient with a three-way translocation
      t(5;8;21). AML1/ETO was also detected in two AML patients lacking the t(8;21)
      cytogenetically. One had a normal diploid karyotype bone marrow (BM) at
      diagnosis; she has now been in CCR for 12 months. The second patient showed a
      complex chromosomal anomaly involving chromosome 21, but without a typical 8;21
      translocation (BM in relapse). He died in relapse after an overall survival of 60
      months. These data indicate that the results of karyotyping and RT-PCR are not
      completely identical, and molecular biology identifies approximately an
      additional 5-10% of AML1/ETO positive cases. The clinical relevance of our
      findings will have to be evaluated with larger patient numbers.

PMID- 9619732
TI  - Comparison of toxicity and outcome in patients with acute myeloid leukemia
      treated with high-dose cytosine arabinoside consolidation after induction with a
      regimen containing idarubicin or daunorubicin.
AB  - The toxicity and outcome after high-dose ara-C/daunorubicin (HDara-C/DNR)
      consolidation therapy in de novo AML was compared in 11 patients who received an
      idarubicin-containing induction therapy (IDA; from June 1995 to March 1997) and
      16 patients pretreated with daunorubicin (DNR; from July 1990 to May 1995) for
      induction. The DNR group consisted of two cohorts, one (n = 6) of patients who
      had received, as had the IDA group, two induction and one intermediate-dose ara-C
      consolidation courses, and another (n = 10) of patients who had been pretreated
      with one induction and one consolidation course prior to HDara-C/DNR. There was
      no difference in the relative dose between the three cohorts. Following HDara
      C/DNR, the IDA-pretreated patients experienced a more prolonged myelosuppression
      during consolidation therapy compared with the DNR group. Duration of neutropenia
      (< 500 neutrophils/microl) following HDara-C/DNR was 31.2 +/- 16 days (mean +/-
      SEM) in the IDA group compared with 18.7 +/- 5 days in the DNR group (p < .001
      Mann-Whitney U-test). The duration 'of thrombocytopenia (platelets <
      25000/microl) was 34.8 +/- 20 days in the IDA group vs. 18.5 +/- 6 days in the
      DNR group (p < .005). The more prolonged myelosupression was associated with a
      longer duration of fever (18.9 +/- 24 vs. 6.9 +/- 5.2 days). A greater incidence,
      length (11 +/- 8 vs. 1.2 +/- 2 days), and severity of diarrhea were observed in
      the IDA-pretreated group. Three of 11 IDA patients experienced WHO grade III-IV
      diarrhea. In the IDA group two patients developed severe enterocolitis with
      Candida septicemia, and one of these patients died. One patient in the IDA group
      died during prolonged aplasia. In the DNR group 6/16 patients experienced grade I
      II diarrhea. Two patients in each group died during consolidation therapy. The CR
      rate was 87% in the IDA group and 79% in the DNR group. Relapse-free survival
      after HDara-C is 50% at a median follow-up of 60 months in the DNR group and 45%
      after a median follow-up of 17 months in the IDA group. Whether the advantage of
      the superior response rate in the IDA-treated patients may be lost during HDara-C
      consolidation treatment due to increased toxicity remains to be proven in larger
      trials.

PMID- 9619734
TI  - Collagen covalently immobilized onto plastic surfaces simplifies measurement of
      von Willebrand factor-collagen binding activity.
AB  - Human collagen type III was immobilized covalently via activated carbohydrate
      moieties onto hydrazine-treated microtiter plates which could be used to measure
      von Willebrand factor (vWF) collagen binding activity (vWF:CBA) in an ELISA. Such
      plates were simple to prepare and remained stable at 4 degrees C and -20 degrees
      C for at least 2 months. Samples analyzed by this system included (a) normal
      human vWF fractionated according to the degree of multimerization, (b) normal
      citrated and EDTA plasma and corresponding serum, and (c) plasma from patients
      with von Willebrand disease (vWD) types 1 and 2. When related to the
      concentration of vWF antigen (vWF:Ag), proportionally low levels of vWF:CBA were
      found for samples lacking the high-molecular-weight multimers, while higher
      values were obtained for samples containing these multimers. The ratio of
      vWF:CBA/vWF:Ag sensitively reflected the functional and structural intactness of
      the vWF molecules for all analyzed samples. Monoclonal antibody directed to the
      region within the A1 domain of vWF which interacts with the glycoprotein Ib
      completely inhibited the vWF ristocetin cofactor (vWF:RistCof), while vWF:CBA was
      not affected. Thus vWF:CBA and vWF:RistCof clearly represent separate,
      noninterchangeable functional parameters of vWF. In conclusion, our results
      indicate that the newly described method for the immobilization of collagen onto
      microtiter plates is suitable for the determination of vWF:CBA. In conjunction
      with vWF:Ag and the calculated ratio of vWF:CBA/vWF:Ag, this method simplifies
      the detection and classification of patients with vWD and assists in quality
      control during the purification of normal vWF.

PMID- 9619733
TI  - Monitoring of hematopoietic recovery after autologous stem cell transplantation
      by analysis of G alpha 16 mRNA and CD34 surface glycoprotein.
AB  - The hematopoiesis-specific G protein alpha subunit G alpha16 was shown to be
      expressed in early normal and malignant hematopoietic cell lines and has been
      suggested to play an important role in signal transduction of hematopoiesis. We
      previously demonstrated a strict correlation of G alpha16 mRNA and CD34 antigen
      expression in peripheral blood stem cells (PBSC). In PBSC mobilization, both
      markers are detectable at the time of hematopoietic recovery and progenitor cell
      release. In this study the possible use of G alpha16 determination in peripheral
      blood samples for monitoring patients undergoing stem cell transplantation was
      investigated. Normal peripheral blood is negative for G alpha16 expression. In
      all five patients G alpha16 mRNA expression appeared shortly before the time of
      blood cell recovery. When tested together with CD34 (three cases) a pattern
      different from CD34 antigen expression was found, reflecting a different
      mechanism of action. In two cases with different time points of leukocyte and
      platelet recovery G alpha16 mRNA was detected at both time points but not in the
      interval, thus suggesting a role of G alpha16 in multipotent precursor cells.
      CD34 mRNA tested in three patients was not detected at any time; this argues for
      different regulation of CD34 and G alpha16 mRNA. G alpha16 may be used as an
      indicator of hematopoietic recovery after autologous stem cell transplantation,
      suggesting that there are cell type-specific G protein-mediated signal
      transduction pathways of early hematopoiesis.

PMID- 9619735
TI  - A case of bone marrow mastocytosis associated with multiple myeloma.
AB  - Mastocytosis is a term used for a spectrum of disorders characterized by abnormal
      growth and accumulation of mast cells. The cutaneous variants of the disease have
      to be distinguished from systemic mastocytosis (SM), in which at least one
      extracutaneous organ is involved. In contrast to cutaneous mastocytosis, SM is
      often associated with another hematologic neoplasm. In most cases clonal myeloid
      malignancies such as a myeloproliferative or myelodysplastic syndrome occur. In a
      few cases of SM, however, clonal lymphoid disorders have been described. We here
      report on a case of SM associated with multiple myeloma. At first presentation,
      the 48-year old female patient showed monoclonal IgGlambda gammopathy and bone
      marrow (BM) mastocytosis, but no BM plasma cell infiltrates. Eight years later,
      the patient presented with BM mastocytosis and overt multiple myeloma. The co
      existence of myeloma and mastocytosis was demonstrable by staining serial BM
      sections with antibodies against mast cell tryptase, CD68R, and the plasma cell
      marker VS38c. Interphase FISH analysis of BM sections revealed a numeric gain of
      chromosome 5 and chromosome 7 in the plasma cells but not in the mast cell
      infiltrates, thereby confirming the presence of two different neoplastic cell
      populations. To our knowledge, this is the first report describing the co
      existence of multiple myeloma and mastocytosis.

PMID- 9619736
TI  - Chronic systemic aspergillosis in a patient with acute myeloid leukemia.
AB  - Systemic aspergillosis is a well-recognized complication of chemotherapy-induced
      neutropenia. In this report a patient with acute myeloid leukemia is described in
      whom a chronic aspergillosis with systemic involvement developed after recovery
      from neutropenia following intensive chemotherapy and allogeneic bone marrow
      transplantation. The clinical features of a chronic course of systemic
      aspergillosis suggest a distinct clinical entity comparable to chronic systemic
      candidiasis.

PMID- 9619737
TI  - Successful treatment of cytomegalovirus encephalitis in a patient with Hodgkin's
      disease in remission.
AB  - Cytomegalovirus encephalitis is a rare but life-threatening infection in non-AIDS
      patients. To our knowledge, no case that followed conventional treatment for
      Hodgkin's lymphoma has been reported. We present a patient with Hodgkin's disease
      in complete remission after combined modality treatment who was succesfully
      treated with a combination of ganciclovir and foscarnet.

PMID- 9619738
TI  - Dietary cancer risk conditional cancerogens in produce of livestock fed on
      species of spurge (Euphorbiaceae). I. Skin irritant and tumor-promoting ingenane
      type diterpene esters in E. peplus, one of several herbaceous Euphorbia species
      contaminating fodder of livestock.
AB  - The hypothesis was proposed that there is a risk of dietary cancer from
      conditional cancerogens in produce of livestock polluted with irritants of the
      diterpene ester type, picked up by feeding on species of Euphorbiaceae (spurge).
      To challenge this, several herbaceous plants of the genus Euphorbia, widespread
      as weeds and contaminants of livestock fodder, were identified botanically and
      extracts of their aerial parts were tested for irritancy on the mouse ear. As
      compared to a standard probe of croton oil, the extracts of E. peplus, E. nubica
      and E. helioscopia displayed irritancy. The most active extract (that from E.
      peplus) was investigated by a fractionation procedure monitored by the mouse ear
      assay, and five molecularly uniform irritant Euphorbia factors Pe1-Pe5 were
      identified as diterpene ester-type toxins. Together these factors comprise at
      least 11 ppm in the aerial parts. They were characterized individually to carry
      the diterpene parent alcohols ingenol, 20-deoxyingenol, and 20-deoxyingenol-6
      alpha, 7alpha-epoxide. The irritancy of the aerial plant parts was shown to be
      caused mainly by the Euphorbia factors Pe1 and Pe2 together. Upon chronic
      administration of these irritants and hyperplasiogens as principal cancerogenic
      risk factors in the mouse skin initiation/promotion bioassay, Pe1 and Pe2 were
      established as tumor promoters. These findings together support the initial
      hypothesis and suggest the need for further investigations to determine whether
      there is a consequent risk of dietary cancer.

PMID- 9619739
TI  - Evaluation of microvessel density by computerised image analysis in human renal
      cell carcinoma. Correlation to pT category, nuclear grade, proliferative activity
      and occurrence of metastasis.
AB  - A high microvessel density is suspected to favour tumour progression and the
      occurrence of metastasis. To elucidate the significance of abundant vessels for
      the behaviour of human renal carcinomas, the microvessel density of 110 renal
      cell carcinomas was correlated to pT category, nuclear grade, proliferative
      activity, occurrence of metastasis and relapse-free survival interval. The
      microvessels were quantified using CD31 immunostaining of endothelial cells and
      computer-aided image analysis. The rules for reproducible microvessel counting,
      as defined by Weidner, were strictly observed. A statistically significant
      relationship between the microvessel density and nuclear grade, proliferative
      activity, occurrence of metastasis and relapse-free survival was found; only for
      tumour size could no such relation be seen. Perplexingly, there is a diminution
      of microvessel density in association with increasing nuclear grade,
      proliferative activity, relapse-free survival interval and frequency of
      metastasis. This finding is contradictory to the hypothesis that an increasing
      microvessel density indicates a worsening prognosis.

PMID- 9619740
TI  - Additive effect of concomitant multiple low-dose doxorubicin and thoracic
      irradiation on ex vivo cardiac performance of the rat heart.
AB  - The effects of doxorubicin alone or combined with local heart irradiation on ex
      vivo cardiac performance were studied in Sprague-Dawley rats. Rats were treated
      with doxorubicin either administered as a single bolus injection or administered
      weekly during a period of 10 weeks. In "combined" experiments, local heart
      irradiation with a single dose of 15 Gy was given prior to drug administration.
      Evaluation of cardiac performance was performed 14 weeks after initiation of
      treatment. At drug doses that were tolerated by the rat, single injections with
      doxorubicin (sd-DXR; up to a dose of 5 mg/kg) did not lead to a change in cardiac
      performance whereas multiple injections with low-dose doxorubicin (mld-DXR; up to
      a cumulative dose of 20 mg/kg) led to a dose-dependent decrease in cardiac
      function. Extracardial toxicity as a result of mld-DXR (cumulative dose < or =15
      mg/kg) was mild when compared to the toxicities observed after sd-DXR (5.0 and
      7.5 mg/kg). When administration of mld-doxorubicin was preceded by 15 Gy, cardiac
      performance further decreased. The present data indicate that the interaction
      between doxorubicin and local heart irradiation with a dose of 15 Gy is additive,
      when the treatments are given concomitantly. Irradiation did not lead to an
      increase of DXR-mediated extracardial toxicities. The isolated working rat heart
      preparation offers a reliable method to evaluate the effects of doxorubicin and
      new anthracycline analogue on the heart.

PMID- 9619741
TI  - The in vitro influence of eight hormones and growth factors on the proliferation
      of eight sarcoma cell lines.
AB  - Little is known about the regulation of sarcoma proliferation by hormones and/or
      growth factors. We therefore characterised the in vitro proliferative influence
      on eight sarcoma cell lines of the platelet-derived growth factor, the insulin
      like growth factor 1, triiodothyronine, the epidermal growth factor, the
      luteinising-hormone-releasing hormone, progesterone, gastrin and 17 beta
      oestradiol. The influence of the different factors on the proliferation of
      sarcoma cell lines was measured by the colorimetric 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide test. Two culture media were studied: (1) a
      nutritionally poor medium containing 2% of fetal calf serum and (2) a
      nutritionally rich one containing 5% or 10% FCS both with and without the
      addition of non-essential amino acids. The results were analysed either by
      conventional statistical analyses or by a classification method based on a
      decision-tree approach developed in Machine Learning. This latter method was also
      compared to other classifiers (such as logistic regression and k nearest
      neighbours) with respect to its accuracy of classification. Monovariate
      statistical analysis showed that each of the eight cell lines exhibited
      sensitivity to at least one factor, and each factor significantly modified the
      proliferation of five or six of the eight cell lines under study. Of these eight
      lines one of fibrosarcoma origin was the most "factor-sensitive". Decision-tree
      related data analysis enabled the specific pattern of factor sensitivity to be
      characterised for the three histological types of cell line under study. The
      effects of hormone and growth factors are significantly influenced by the type of
      culture medium used. The method used appeared to be an accurate classifier for
      the kind of data analysed. Sarcoma proliferation can be modulated, at least in
      vitro, by various hormones and growth factors, and the proliferation of each
      histopathological type exhibited a distinct sensitivity to different hormone
      and/or growth-factors.

PMID- 9619743
TI  - Improved therapeutic response by distinct timing of multiple heat treatments
      during interstitial radiation in the Dunning R3327 prostate tumor model.
AB  - PURPOSE: As a continuation of a previous study showing the efficacy of a single
      local tumor heat treatment (LTH) in combination with interstitial radiation (IR)
      in the Dunning tumor system R3327 (subline AT1), we evaluated higher doses and/or
      lower dose rates with an extended time course of IR treatment, which allowed
      greater flexibility for LTH applications. METHODS: IR was carried out by the
      insertion of one removable 192Ir seed into the center of a R3327-AT1 tumor,
      transplanted s.c. into the distal thigh of Copenhagen rats. LTH (43.5 degrees C,
      for 35 min) varied from one treatment just before IR to multiple applications
      beginning at 0 h and repeated every 48 h or 72 h. RESULTS: The Dunning subline
      R3327-AT1 is a very thermoresistant tumor, which did not reveal any thermal
      response when heated up to 44.5 degrees C for 35 min. IR alone produced a delay
      in tumor growth, related to dose and dose rates of 18-53 cGy/h. During longer
      treatment times, a single LTH just before the IR was no more effective than IR
      alone. Thermoradiotherapy with multiple LTH treatments given at intervals of
      between 48 h and 72 h resulted in a clear increase in growth delay.
      Radiosensitization was highest in all dose-rate groups where LTH was applied
      every 72 h during a complete course of IR. CONCLUSIONS: These results demonstrate
      the importance of administering a sequence of multiple applications of LTH during
      continuous low-dose-rate irradiation and they substantiate our earlier findings,
      with shorter exposure times, where one LTH given every 72 h appeared to be most
      efficient in the combined treatment of the Dunning rat prostate tumor R3327-AT1.

PMID- 9619742
TI  - On telomere shortening in soft-tissue tumors.
AB  - PURPOSE: Specific simple DNA repeats occur at the telomeric ends of mammalian
      chromosomes. Loss of (G + C)-rich repeats can result in genetic instability,
      associated with tumorigenesis. So far, data on telomere shortening have not been
      available for different types of soft-tissue tumors. METHODS: Using tumor
      material and the blood of the corresponding patient, high-molecular-mass DNA was
      prepared by digestion with proteinase K and extraction with phenol/chloroform. A
      10-microg sample of DNA was digested with the restriction enzyme HinfI. DNA
      fragments were separated in a 0.7% agarose gel, and in-gel hybridization was
      performed with the telomere-specific repeat probe (TTAGGG)3. RESULTS: Shortening
      of the telomere repeat was observed in 14/30 soft-tissue tumors; 5 tumors showed
      elongated telomere repeats, whereas the telomeres appeared unchanged in 11
      tumors. Decreased telomere repeat length correlated with advanced age, DNA
      ploidy, and a higher proliferation index. There was no association between
      telomere repeat length and tumor grade. Interestingly, in contrast to other
      entities, all malignant schwannomas and leiomyosarcomas showed significantly
      reduced telomere lengths. An explanation for the telomere heterogeneity in
      liposarcomas may include differential telomerase reactivation in well and poorly
      differentiated tumors. CONCLUSIONS: Telomere shortening is frequent but not a
      uniform phenomenon in different types of soft-tissue tumor. Studies on telomerase
      activity should be performed in the same cohort of sarcomas.

PMID- 9619744
TI  - Dietary cancer risk from conditional cancerogens in produce of livestock fed on
      species of spurge (Euphorbiaceae). II. Pathophysiological investigations in
      lactating goats fed on the skin irritant herb Euphorbia peplus and in their milk
      raised kids.
AB  - Lactating goats were fed on aerial parts of the herb Euphorbia peplus L. admixed
      with their usual green fodder. During the experimental feeding period they showed
      symptoms of general poisoning. In necropsy the main toxic effects were seen in
      the heart, lung and liver. Histopathological examinations revealed that the
      primary toxic effects originated from degenerative changes in parenchymal and
      endothelial cells. Adverse symptoms in the liver and kidney were also reflected
      in an alteration of the levels of certain serum enzymes and of blood urea
      nitrogen. The milk of the goats fed on E. peplus, consumed by their young kids,
      caused poisoning and even death, with signs similar to those observed in the
      adult dams. These observations support the hypothesis that the poisoning observed
      in both milk-raised kids and mother goats is caused by diterpene ester type
      toxins present in the aerial parts of the herb contaminating the dams fodder.
      Generally, such skin irritant and hyperplasiogenic toxins are known to be highly
      active tumour promoters of skin and other organ, e.g. in mice. Lactating goats-
      as an important source of milk around the world--in a setting similar to that
      described, may provide a valid experimental etiological model for investigation
      of food polluted by tumour-promoting diterpene ester toxins.

PMID- 9619745
TI  - Plasma lipid alterations in African-American women with breast cancer.
AB  - The purpose of this study was to examine the relationship between plasma lipid
      and lipoprotein levels, stage of disease and breast cancer risk in African
      American women. The study population comprised 163 African-American women:
      patients (n = 58) and controls (n = 105), with mean ages of 57.2 years and 47.7
      years respectively. Approximately 71% and 56% of the women with breast cancer and
      the control population, respectively, were postmenopausal. Those with cancer had
      significantly higher education levels, P < or = 0.01, and higher triglyceride
      levels compared to the controls, P < or = 0.001, but lower body mass index (BMI)
      levels, P < or = 0.01. There were no statistically significant differences
      observed in total cholesterol, high-density-lipoprotein-containing cholesterol
      and low-density-lipoprotein-containing cholesterol between the patients and
      controls. After adjustments for age, education, BMI, and menopausal status,
      triglycerides remained significantly and positively associated with breast cancer
      risk. The significant correlation between the high levels of triglycerides and
      breast cancer risk (odds ratio = 5.12) may be attributed to differences in lipid
      metabolism between the women with breast cancer and controls, or to the
      consequences of breast cancer.

PMID- 9619746
TI  - 5-Fluorouracil plus interferon alpha-2a compared to 5-fluorouracil alone in the
      treatment of advanced colon carcinoma: a multicentric randomized study.
AB  - Biochemical modulation is one of the most interesting fields in cancer
      chemotherapy. Interferon-alpha (IFNalpha) is a cytokine that is able to influence
      the pharmacodynamics of 5-fluorouracil (5FU) through a number of mechanisms. With
      the aim of confirming some data emerging from the literature, we initiated a
      multicentric randomized study comparing the combination of 5FU and IFNalpha-2a
      with 5FU alone in the treatment of advanced or metastatic colon cancer. A group
      of 205 colon cancer patients (104 in the 5FU arm and 101 in the 5FU + IFNapha-2a
      arm) were included in the final intention-to-treat analysis. Rectal cancers were
      not considered eligible. All patients had measurable disease, were aged 75 years
      or less, had a Karnofsky index of at least 60 and had good bone marrow, renal,
      liver and cardiac functions. No previous chemo-immunotherapy was allowed. The
      treatment was 750 mg/m2 5FU (4 h i.v. infusion) on days 1 5 and then i.v. bolus
      weekly, starting from day 12, with or without IFNalpha-2a given s.c. three times
      weekly (starting dose 3 x 10(6) IU rising to 9 x 10(6) IU, if tolerated).
      Patients were treated until progression or, if responsive, for a maximum of 48
      weeks and then observed for a period of 2 years. The primary end-point of the
      study was objective clinical response (OR); secondary parameters were time to
      progression, overall survival, and time to death after progression. WHO criteria
      were used for both clinical response and toxicity measurements. Dose reduction
      was planned a priori in the event of significant toxicity due to 5FU, IFNalpha-2a
      or both. Association between primary and secondary end-points and treatment was
      studied by univariate and multivariate analysis. Altogether, 47 patients achieved
      a documented response. A 25% OR was observed in the combination arm while a 21%
      OR was seen in the 5FU arm; this difference is not statistically significant (P =
      0.6). Patients with a small tumour burden (below 5 cm2) showed a higher
      probability of response in both arms. Patients in the experimental arm had a
      higher but not statistically significant cumulative progression-free probability.
      Median survival was 47.1 weeks overall, while it was 43.7 and 48.5 weeks in the
      control and experimental arms, respectively. The combination was clearly more
      toxic than 5FU alone, leukopenia being the most frequent side-effect in the
      experimental arm and nausea and vomiting in the control arm. In conclusion these
      results are quite disappointing and 5FU + IFNalpha-2a can not be considered a
      standard treatment for advanced colon cancer.

PMID- 9619747
TI  - Survival in patients with primary soft-tissue sarcomas treated within 6 years.
AB  - Since 1988, treatment strategies for our sarcoma patients have been determined by
      the same team and operations performed by one surgeon. The aim of this study was
      to analyse prognostic data on local recurrence and survival of 101 consecutive
      patients who presented in our institution with the primary tumour manifestation.
      After a median follow-up of 35 months, the local recurrence rate was 13.5%, the
      mean survival time was 68 months and the 5-year survival rate was 83%. Besides
      positive lymph nodes (only 3 patients) the quality of resection significantly
      influenced local recurrences (P < 0.05). Univariate predictors of mortality were
      tumour grade (P < 0.01), tumour size (P < 0.05), distant metastases (P < 0.01),
      and resection quality (P < 0.01). Multivariate predictors of mortality consisted
      of grade (P < 0.0001), positive lymph nodes (P < 0.001) and resection quality (P
      < 0.01). In this homogeneous group of patients, excellent recurrence and survival
      rates could be achieved. An optimized surgical treatment not only reduces the
      rate of local recurrences but also augments survival time.

PMID- 9619748
TI  - Risk of secondary myeloid leukemia and myelodysplastic syndrome following
      standard-dose chemotherapy or high-dose chemotherapy with stem cell support in
      patients with potentially curable malignancies.
AB  - Secondary acute myeloid leukemia (s-AML) and secondary myelodysplastic syndrome
      (s-MDS) probably represent the worst possible long-term complications of cancer
      therapy in patients originally cured of their primary malignancy. The frequency
      and type of s-AML and s-MDS are reviewed for patients treated with standard
      and/or high-dose chemotherapy for Hodgkin's disease, non-Hodgkin's lymphoma
      (NHL), and breast or testicular cancer. Patients treated for Hodgkin's disease,
      have a 20- to 40-fold increased risk of developing s-AML, this risk increasing
      with the number of mechlorethamine-containing cycles given as well as following
      splenectomy and in patients more than 40-50 years of age. Generally, patients
      with NHL, breast or testicular cancer experience a lower, 2- to 15-fold, risk of
      developing s-AML. Epipodophyllotoxins appear to be the most important factor for
      s-AML in patients treated for testicular cancer. Doses of 2g/m2 or more are
      associated with an increased risk of s-AML and, with these high doses, a
      cumulative incidence of 2% 3% at 5 years is observed. Adjuvant cyclophosphomide,
      methobrexate, 5-Fu therapy in breast cancer patients does not appear to increase
      risk significantly as compared to the general population. The extent of the
      leukemogenic potential of anthracyclines remains to be defined. NHL patients
      receiving mechlorethamine, prednimustine or long-term maintenance therapy are
      also at an increased risk of s-AML. A considerably increased risk of developing
      AML, with a cumulative incidence of approximately 9% at 5 years, has been
      observed following allogenic bone marrow transplantation (ABMT) or peripheral
      stem cell transplantation (PBSCT) in patients with NHL. It is likely that the
      increased risk of s-AML/s-MDS following high-dose chemotherapy with ABMT or PBSCT
      is related to prior treatment rather than to high-dose chemotherapy itself.
      However, this issue remains to be conclusively addressed. s-AML or s-MDS rarely
      develops after allogenic bone marrow transplantation. s-AML and s-MDS
      increasingly represent a problem in modern cancer therapy because of better
      treatment strategies, which result in improved cure rates. Patients who receive
      chemotherapy must be informed about the potential risk of developing s-AML or s
      MDS. Future studies should include a follow-up long enough to record the
      occurrence of all s-AML/s-MDS and all potential influencing factors reliably.
      These data would enable risk factors to be defined and risk/benefit analyses to
      be carried out, allowing the correct assessment of current and future therapy
      strategies.

PMID- 9619749
TI  - Pretreatment serum lactate dehydrogenase as additional staging parameter in
      patients with small-cell lung carcinoma.
AB  - PURPOSE: At present the standard staging procedure in patients with small-cell
      lung cancer (SCLC) is extensive, expensive and time-consuming. Furthermore, the
      predictive and prognostic value of the current staging system is poor. To
      determine the value of pretreatment clinical and biochemical parameters to
      predict tumour stage and to assess prognosis, a retrospective study was performed
      of 121 consecutive patients with newly diagnosed SCLC. METHODS: On the basis of
      routine diagnostic procedures, 51 patients were staged as having limited disease
      and 70 patients as having extensive disease. During follow-up, data on tumour
      progression and survival were gathered. These data and the tumour stage were
      correlated with lactate dehydrogenase (LDH), alkaline phosphatase, liver enzymes,
      leucocyte count, protein, albumin, calcium, age and gender. RESULTS: Follow-up
      ranged from 1 week to 96 months, during which 110 patients died. In all patients
      with LDH levels above 400 U/l (n = 31), metastases were found at the initial
      stage, whereas all patients initially staged as having limited disease and LDH
      levels above 240 U/l showed tumour progression. Bone and liver were found to be
      the most commonly involved sites, whereas the incidence of brain metastases
      increased during follow-up. In patients initially staged as having limited
      disease, no differences in survival were found between those showing local
      recurrence and those developing metastases during follow-up (P = 0.67). Compared
      to the patients initially staged as having extensive disease, the survival of
      both groups was significantly better (P < 0.001). Significant independent
      variables of survival were LDH, albumin, initial stage and gender, but LDH was
      the best overall predictor (P < 0.001). CONCLUSION: These results suggest that
      pretreatment LDH may be used as an additional staging parameter in SCLC, which
      can identify prognostic subgroups before treatment.

PMID- 9619750
TI  - XIX Symposium of the International Association for Comparative Research on
      Leukemia and Related Diseases, July 13-18 Mannheim/Heidelberg, Germany, 1997.

PMID- 9619751
TI  - Pharmacokinetic study of low- versus high-dose medroxyprogesterone acetate (MPA)
      in women.
AB  - The present study was conducted to compare the pharmacokinetics (PK) of low-dose
      versus high-dose medroxyprogesterone (MPA) as a once-daily oral administration.
      Of 32 patients, all women, enrolled in this PK study, 18 received 600 mg MPA
      daily and 14 received 1200 mg daily. Detailed PK data were obtained on day 1 and
      after more than 4 weeks of MPA treatment. In addition, multiple data for the
      minimum steady-state concentration (Css min) were analyzed. The MPA serum
      concentrations were measured by high-performance liquid chromatography. Wide
      interpatient variability was found in the PK parameters obtained both on day 1
      and after more than 4 weeks. There were no clear relationships between the oral
      dose and the MPA peak concentration (Cmax), area under the time versus
      concentration curve (AUC), or mean Css min. Weight gains of 10% or more were
      demonstrated more frequently in the high-dose group (P < 0.01). Liver dysfunction
      (n = 5) did not influence the PK of MPA. Five patients demonstrated extremely low
      AUC and Cmax (< 10 ng/ml) values on day 1. Phenobarbital, dexamethasone and
      betamethasone were being taken concomitantly with the MPA each by one patient.
      The serum MPA concentrations were markedly increased after the discontinuation of
      phenobarbital in that patient, suggesting a drug interaction. At present we
      cannot recommend the high dose of MPA, except in clinical studies, from a PK or a
      pharmacodynamic points of view.

PMID- 9619752
TI  - Reversal of multidrug resistance by a liposome-MDR1 ribozyme complex.
AB  - PURPOSE: Multidrug resistance (MDR) is a major obstacle in cancer chemotherapy.
      We examined whether cationic liposome-mediated transfer of a ribozyme could
      reverse MDR. METHODS: A ribozyme which cleaved codon 196 of MDR1 mRNA was
      constructed from synthetic oligonucleotides. The MDR1 ribozyme was mixed with N
      (1-(2,3-dileoyloxy)propyl)-N,N,N-trimethylammonium methyl sulfate (DOTAP) to form
      a liposomal complex. The complex was used to treat two P-glycoprotein-producing
      MDR cell lines: MCF-7/R human breast cancer cells resistant to doxorubicin and
      MOLT-3/TMQ800 human ALL cells resistant to trimetrexate (TMQ). In order to
      investigate the differential sensitivity of these two cell lines to the liposome
      ribozyme complex, cellular pharmacological studies including phase-contrast and
      confocal microscopic studies were performed. RESULTS: Treatment with the liposome
      ribozyme complex resulted in reversal of vincristine (VCR) resistance in MCF-7/R
      cells, but not in MOLT-3/TMQ800 cells. In MCF-7/R cells the treatment resulted in
      decreases in MDR1 mRNA expression and P-glycoprotein production, whereas no
      changes in these parameters were seen in MOLT-3/TMQ800 cells. Phase-contrast
      microscopy revealed that in MCF-7/R cells treatment with DOTAP led to the
      formation of cytoplasmic vacuoles, and treatment with latex beads resulted in the
      development of a shiny material in the cytoplasm. In contrast, in MOLT-3/TMQ800
      cells hardly any morphological changes occurred. Confocal microscopic imaging
      showed cytoplasmic fluorescence in MCF-7/R cells after treatment with DOTAP/FITC
      dextran or FITC-conjugated latex beads. In MOLT-3/TMQ800 cells no fluorescence
      was detected. Treatment with cytochalasin B abolished fluorescence in MCF-7/R
      cells after treatment with DOTAP/FITC-dextran or FITC-conjugated latex beads.
      These studies show that MCF-7/R cells have high endocytotic activity whereas MOLT
      3/TMQ800 cells have little activity. CONCLUSIONS: Endocytotic activity was
      correlated with the success of cationic liposome-mediated transfer of MDR1
      ribozyme. Determination of endocytotic activity of target tumor cells may be
      predictive of efficacy of liposome-mediated gene transfer.

PMID- 9619753
TI  - Toxicity of cytostatic drugs to normal bone marrow cells in vitro.
AB  - In this study we compared how different concentrations and periods of incubation
      of anthracyclines, amsacrine, and cytosine arabinoside would affect normal
      hematopoietic bone marrow cells in terms of interindividual differences in
      toxicity, the age of the donor, and the proliferative capacity of the bone
      marrow. Bone marrow was obtained from 36 donors in connection with bone marrow
      transplantation. After separation the mononuclear cell fraction was incubated
      with doxorubicin, 4-epidoxorubicin, daunorubicin, idarubicin, aclarubicin,
      mitroxantrone, amsacrine, and cytosine arabinoside for 1 h, for 3 h, or
      continuously. The cells were thereafter cultured in soft agar and CFU-GM were
      counted after 10-12 days. The results showed a large interindividual variation in
      toxicity for all drugs tested. Daunorubicin, idarubicin, aclarubicin, and
      mitoxantrone had a pronounced cytotoxic effect after 1 h of incubation.
      Doxorubicin and 4-epi-doxorubicin showed the greatest cytotoxic effect after 3 h
      and were also more toxic to normal bone marrow cells from donors over 40 years of
      age. Ara-C had a low cytotoxic effect after 1 and 3 h of incubation, even at high
      concentrations, but exerted a pronounced degree of toxicity during continuous
      incubation. Daunorubicin, idarubicin, and ara-C also showed increased toxicity to
      cell samples with a low proliferating capacity in the control. The conclusions
      drawn from these results are that interindividual variation, proliferation
      capacity, incubation conditions, and the age of the donors are factors of
      importance in the toxicity of drugs to normal hematopoietic bone marrow cells.

PMID- 9619754
TI  - Allosteric effectors of hemoglobin as modulators of chemotherapy and radiation
      therapy in vitro and in vivo.
AB  - INTRODUCTION: A series of molecules designed to be allosteric effectors of
      hemoglobin were examined for their potential as radiation sensitizers in vitro
      and in vivo and for their potential as chemosensitizers in vivo as well as for
      their antimetastatic effect. RESULTS: At a concentration of 100 microM for 1 h
      prior to, during and for 1.5 h after radiation exposure, the allosteric effectors
      decreased the shoulder of the radiation survival curve of normally oxygenated EMT
      6 cells and increased the slope of the radiation survival curves of hypoxic EMT-6
      cells resulting in dose-modifying factors of 1.8 to 2.1. In vivo the allosteric
      effectors had antitumor activity against the Lewis lung carcinoma and produced
      primarily additive tumor growth delay when administered along with fractionated
      radiation therapy. When administered on days 4 through 18 after tumor
      implantation, the allosteric effectors, especially JP-7, RSR-13 and RSR-4, were
      highly effective antimetastatic agents in animals bearing Lewis lung carcinoma.
      In cell culture, simultaneous exposure to the allosteric effectors (at 100
      microM) effectively sensitized EMT-6 cells to the effects of 4
      hydroperoxycyclophosphamide, thiotepa and carboplatin. The allosteric effectors
      were not very cytotoxic toward EMT-6 tumor cells from tumors treated in vivo with
      single doses of each molecule nor were these agents very cytotoxic toward bone
      marrow CFU-GM taken from the same animals. CONCLUSIONS: It is likely that the
      allosteric effectors have a molecular target in addition to hemoglobin. Other
      possible targets include hydroxymethyl-glutaryl-CoA reductase or microsomal
      cytochrome b5.

PMID- 9619755
TI  - FK317: a novel substituted dihydrobenzoxazine with potent antitumor activity
      which does not induce vascular leak syndrome.
AB  - PURPOSE: FK973, a substituted dihydrobenzoxazine, is an antitumor antibiotic
      which has shown high therapeutic efficacy in a phase I study, but its development
      has been abandoned because of the side effect of vascular leak syndrome (VLS) in
      the clinical study. This study was performed to investigate whether or not FK317,
      a new benzmethoxy derivative of FK973, retains the antitumor activity of FK973
      without the side effect of VLS. METHODS: VLS was evaluated by the volume of
      pleural effusion in rats. Cytotoxic activities were determined by a tetrazolium
      based colorimetric assay (MTT assay) against murine (B16, P388) and human (HeLa
      S3, KB) tumor cell lines. Antitumor activities against murine ascitic leukemia
      (P388, L1210), murine solid tumors (reticulum cell sarcoma M5076, Colon 38
      carcinoma) and human xenografts (mammary carcinoma MX-1, lung carcinoma LX-1)
      were examined. RESULTS: FK973 (1.8 mg/kg) given i.v. to rats induced pleural
      effusion, one of the elements of VLS, 36 days after the first dosing, but did not
      28 days after dosing. This model reflects clinical VLS delayed-type effusion with
      high protein concentrations. In contrast, FK317 (1.0-3.2 mg/kg) did not induce
      pleural effusion at all. FK317 had stronger cytotoxic effects against in vitro
      cultured B16, P388, HeLa S3 and KB tumor cell lines, and in in vivo experiments,
      FK317 showed equivalent antitumor activity against P388, M5076 and MX-1, and more
      potent antitumor activity against L1210, Colon 38 and LX-1 compared with FK973.
      CONCLUSION: These results suggest that FK317 retains the antitumor activity of
      FK973 and does not induce VLS, and FK317 is a drug with high clinical potential
      for treating tumors in humans.

PMID- 9619756
TI  - Renal toxicity of the neuron-blocking and mitochondriotropic agent m
      iodobenzylguanidine.
AB  - meta-Iodobenzylguanidine (MIBG) is a multipotent drug used in its radiolabeled
      form as a tumor-seeking radiopharmaceutical in the diagnosis and treatment of
      pheochromocytoma and neuroblastoma. Nonradiolabeled MIBG has also proved to be
      effective in the palliation of carcinoid syndromes and, on a predosing schedule,
      in enhancing the relative tumor uptake of a subsequent [131I]-MIBG dose in tumors
      of neuroadrenergic origin. In addition, MIBG is under investigation as an
      inhibitor of mitochondrial respiration and, as such, for its use in tumor
      specific acidification. In this report we describe the side effects of
      nonradiolabeled MIBG on kidney function in mice. High doses of MIBG (40 mg/kg)
      reduced renal blood perfusion as measured by 86Rb distribution by 50%, which
      could be antagonized by the bioamine receptor blockers prazosin and
      cyproheptadine. MIBG also induced reversible renal damage as evidenced from a
      decrease in [51Cr]-ethylenediaminetetraacetic acid (EDTA) clearance and from
      histological damage, which was most pronounced in the distal tubuli. These
      effects were unrelated to reduced perfusion, however, and could not be
      antagonized by bioamine receptor blockers, Ca2+-channel blockers, or diuretics.
      Clearance effects of MIBG were mimicked by N-nitro-L-arginine methyl ester (L
      NAME), a known inhibitor of nitric oxide synthase (NOS), and MIBG itself (100
      microM) also inhibited NOS in vitro, suggesting that NOS inhibition by MIBG may
      have contributed to the observed reduction in renal clearance. The MIBG analog
      benzylguanidine (BG), which is equipotent in terms of mitochondrial inhibition,
      did not affect renal clearance, thus excluding mitochondrial inhibition as the
      main mechanism of MIBG-induced damage. MIBG, however, was much more cytotoxic
      than BG to kidney tubular cells in primary cultures. Although the renal effects
      of high-dose MIBG were reversible, alterations in the pharmacokinetics of
      concomitant medications by a temporary reduction in renal function should be
      taken into account in its clinical application.

PMID- 9619757
TI  - Influence of treatment with aminoglutethimide on plasma and red-blood-cell
      glutathione status in breast cancer patients.
AB  - PURPOSE: Elevated cellular glutathione has been associated with resistance to
      cancer chemotherapy. Treatment with the aromatase inhibitor aminoglutethimide
      increases the concentration of gamma-glutamyl transpeptidase (gamma-GT) in breast
      cancer patients. This enzyme catalyzes the first step in the degradation of
      extracellular glutathione, and the products formed may act as precursors for
      intracellular glutathione synthesis. METHODS: Plasma and red-blood-cell
      glutathione levels were determined in 26 patients suffering from advanced breast
      cancer before and during treatment with aminoglutethimide (n = 16) or the
      steroidal aromatase inhibitors exemestane or formestane (n = 10) and in 5 cancer
      patients receiving dexamethasone. RESULTS: Pretreatment values for gamma-GT in
      the total patient group (n = 31) correlated negatively with the level of reduced
      (P < 0.0001), oxidized (P < 0.025), and total glutathione (P < 0.005) in plasma.
      Plasma gamma-GT levels increased by a mean value of 249% during treatment with
      aminoglutethimide. The concentration of reduced and oxidized glutathione in
      plasma decreased to 42.7% (P < 0.0005) and 80.6% (P < 0.005) of their
      pretreatment levels, respectively. This fall in reduced plasma glutathione
      correlated negatively with the increase in gamma-GT (P < 0.001). The ratio of
      oxidized to reduced glutathione increased by 88.9% (P < 0.005), and this increase
      correlated positively with the increase in gamma-GT (P < 0.005). Treatment with
      the steroidal aromatase inhibitors (exemestane and formestane) or dexamethasone
      did not influence the plasma thiol status. CONCLUSIONS: We conclude that
      aminoglutethimide influences plasma glutathione disposition by mechanisms not
      related to estrogen suppression or due to glucocorticoids given in concert.

PMID- 9619758
TI  - Irinotecan (CPT-11) in combination with weekly administration of cisplatin (CDDP)
      for non-small-cell lung cancer.
AB  - PURPOSE: CPT-11 (60 mg/m2 on days 1, 8 and 15) in combination with CDDP (80 mg/m2
      on day 1) has shown promising antitumor activity for non-small-cell lung cancer
      (NSCLC), but dose-limiting toxicities (DLT) are leukopenia and diarrhea, with a
      wide variation among patients. To estimate weekly CDDP administration in
      combination with CPT-11, a phase I study for patients with advanced NSCLC was
      conducted. METHODS: Patients were treated with CPT-11 at a fixed dose of 60 mg/m2
      together with CDDP at 27 mg/m2 (level 1, 6 patients), 33 mg/m2 (level 2, 12
      patients), and 40 mg/m2 (level 3, 6 patients) with 1600 ml hydration on days 1, 8
      and 15 over 4 weeks. During the treatment course, drug was not administered on
      the day it was due in the presence of leukopenia (< 3000/ml) and/or diarrhea.
      RESULTS: The planned administration was completed in 5 of 6 patients at level 1,
      6 of 12 patients at level 2, and 2 of 6 patients at level 3. The most common
      toxicity observed was leukopenia (five patients with grade 3 and one patient with
      grade 4). Leukopenia was considered to be a DLT, and the maximum tolerated dose
      (MTD) was level 2. Although there were patients who suffered from diarrhea (four
      patients with higher than grade 2), diarrhea was judged not to be a DLT with this
      weekly regimen. Nausea and vomiting were mild. Pharmacokinetic analysis of free
      platinum from CDDP demonstrated that the area under the curve (AUC) from 33 mg/m2
      CDDP was 0.92 +/- 0.29 microg/ml h. In 13 patients evaluated for response, the
      response rate was 54%. CONCLUSION: The value of weekly administration of CDDP in
      combination with CPT-11 was shown by (1) diarrhea not being dose-limiting, (2)
      mild nausea, (3) well-maintained AUC of free platinum, and (4) promising
      activity.

PMID- 9619759
TI  - Comparative studies between the effects of mitozolomide and two novel
      tetrazepinones PYRCL and QUINCL on NIH:OVCAR-3 cells.
AB  - Cytotoxicity, reduction of macromolecule synthesis and cell cycle perturbations
      by two novel 3-(2-chloroethyl)-tetrazepinones, PYRCL and QUINCL were compared
      with those produced by the structurally related 3-(2-chloroethyl)-tetrazinone,
      mitozolomide, in the OVCAR-3 cell line. METHODS: Macromolecule synthesis was
      determined by incorporation of 3H-thymidine, 3H-uridine and 3H-leucine into acid
      precipitable fractions of OVCAR-3 cell extracts. Maxam-Gilbert sequencing was
      used to compare the DNA alkylating sites induced by the tetrazepinones, with
      those created by mitozolomide. Alkaline sucrose-density sedimentation was
      employed to detect genomic DNA damage. Also, the effects of the tetrazepinones on
      the cell cycle were determined by univariate flow cytometry. RESULTS: At 3 h post
      treatment, mitozolomide appeared as a selective inhibitor of DNA synthesis, while
      both tetrazepinones inhibited the synthesis of all three macromolecules. At 24 h
      post-treatment, the inhibition of DNA synthesis was observed to increase in cells
      treated with mitozolomide, while it decreased in those previously exposed to the
      tetrazepinones. Also at 24 h post-treatment, mitozolomide induced accumulation of
      cells in S(late)/G2M at low concentrations and in S-middle at high
      concentrations. In contrast, at the same recovery time, cells treated with the
      tetrazepinones accumulated specifically in G2M, the strength of the block being
      dose-dependent. At an equimolar concentration, the tetrazepinones induced weaker
      guanine N-7 alkylation than mitozolomide. By 24 h after treatment, cells exposed
      to the tetrazepinones showed significantly greater DNA fragmentation than those
      previously treated with mitozolomide. CONCLUSION: In summary, based on (a) their
      effects on DNA, RNA, protein synthesis and on the cell cycle, (b) their
      alkylating power and (c) their interactions with DNA, the 3-(2
      chloroethyl)tetrazepinones appeared to kill tumor cells by a novel mechanism
      which may significantly differ from that of their 3-(2-chloroethyl)-tetrazinone
      counterpart, mitozolomide.

PMID- 9619760
TI  - Tomudex (ZD1694, NSC 639186) in platinum-pretreated recurrent epithelial ovarian
      cancer: a phase II study by the Gynecologic Oncology Group.
AB  - PURPOSE: Tomudex is a second-generation folate analogue that when polyglutamated
      is a potent inhibitor of thymidylate synthase (TS). METHODS: Based on indications
      of antitumor activity in phase I trials, the Gynecologic Oncology Group initiated
      a phase II study of Tomudex 3 mg/m2 intravenously every 3 weeks in patients with
      epithelial ovarian cancer, who had been pretreated with platinum drugs, and had
      subsequently recurred more than 6 months following such treatment. RESULTS: Of 30
      patients entered into the trial, 2 were pathologically ineligible, leaving 28
      fully evaluable. In this patient population, Tomudex was generally well
      tolerated, but only three objective (partial) responses were documented.
      CONCLUSIONS: With the level of activity seen, the drug was not considered for
      further clinical development in ovarian cancer by the Gynecologic Oncology Group.
      However, it may be worthwhile to explore whether quantitation of TS could lead to
      selection of patients more likely to respond to this TS inhibitor.

PMID- 9619761
TI  - Metabolism, excretion and pharmacokinetics of a single dose of [14C]-raltitrexed
      in cancer patients.
AB  - Raltitrexed (Tomudex) is a specific inhibitor of thymidylate synthase and has
      recently been licensed in Europe for use in the treatment of advanced colorectal
      carcinoma. This study evaluated the metabolism, excretion and pharmacokinetics
      after a single dose of 3.0 mg/m2 [14C]-raltitrexed in patients with advanced
      solid malignancies not amenable to curative therapy. From April 1994 to July
      1995, nine patients (six men and three women) were recruited into the study.
      Pharmacokinetics analysis was performed during the first cycle of treatment in
      all patients and, in two patients, limited sampling was done prior to and during
      the second cycle of treatment. The mean observed peak plasma concentration (Cmax)
      was 700.6 ng/ml and the median time (tmax) to reach maximal raltitrexed
      concentrations was 15 min after the initiation of the infusion. After reaching
      Cmax the drug declined in a triexponential manner with a terminal half-life of
      257 h. The AUC0-infinity as predicted by the pharmacokinetic model was 2341.7 ng
      h ml(-1). Clearance was 41.3 ml/min, of which renal clearance accounted for 50
      60%. Urinary collection for the measurement of radiolabeled drug revealed that
      renal excretion extrapolated to infinity accounted for 40% of the total
      radioactive dose. Faecal excretion accounted for only 3% of the dose when samples
      were collected to day 5 in the first six patients. Collection was extended to 10
      days in the last three patients and faecal elimination accounted for 14% in these
      patients. Raltitrexed measurements prior to subsequent doses suggest that there
      was no accumulation of the drug with repeated administration. Low levels of
      radioactivity measured in the red cell pellets on days 15, 22 and 29 are likely
      to represent drug retained by newly forming red cells at the time of dosing.
      Examination of the urine revealed that the drug was excreted unchanged. The
      toxicities seen were in line with those encountered in previous studies. Grade 3
      and 4 thrombocytopenia occurred in three patients and grade 3 neutropenia
      occurred in two patients.

PMID- 9619762
TI  - Apoptosis- and necrosis-inducing potential of cladribine, cytarabine, cisplatin,
      and 5-fluorouracil in vitro: a quantitative pharmacodynamic model.
AB  - PURPOSE: The purpose of this study was to characterize the concentration
      dependent induction of apoptosis by anticancer drugs in vitro. METHODS: The
      apoptosis- and necrosis-inducing potential of the anticancer drugs cladribine
      (CDA), cytarabine (ARA-C), cisplatin (CDDP), and 5-fluorouracil (5FU) were
      studied in vitro in the human leukemia cell lines HSB2 and Jurkat using a flow
      cytometry assay that permits the simultaneous quantification of vital, apoptotic,
      and necrotic cells by double-staining with fluorescein isothiocyanate (FITC)
      labeled Annexin-V and propidium iodide. The results were fit to different
      multicompartmental models and the sensitivity of the cell lines to apoptosis and
      necrosis was estimated. RESULTS: A time- and dose-dependent decrease in vital
      cells as well as an increase in apoptotic and necrotic cells was observed in HSB2
      cells upon continuous incubation with 10(-5)-10(-7) MCDA, 10(-5)-10(-8) MARA-C, 5
      x10(-5)-5 x 10(-6) M CDDP, and 10(-4)-10(-5) M 5FU, whereas no effect was
      observed relative to controls upon incubation with 10(-8)-10(-9) M CDA, 10(-9) M
      ARA-C, 10(-7)-10(-8) M CDDP, or 10(-6)-10(-9) M 5FU. In Jurkat cells, apoptosis-
      and necrosis-inducing effects were observed at 10(-4)-5 x 10(-6) M CDA, 10(-5)
      10(-7) M ARA-C, 5 x 10(-5)-5 x 10(-6) M CDDP, and 10(-4)-10(-5) M 5FU. In all
      experiments, apoptotic cells reached a peak after 6-48 h of drug exposure. These
      data were best fit by a model in which vital cells became irreversibly apoptotic
      by a direct pathway and necrotic by an irreversible indirect pathway following
      the apoptotic state (mean R = 0.9876; range 0.9510-0.9993; mean modified Akaike's
      information criterion 3.88; range 1.86-5.82) and the rate constants of either
      pathway (Kva and Kan, respectively) were assessed. The sensitivity of both cell
      lines to apoptosis and necrosis (expressed as EC50 and Emax values) induced by
      the anticancer drugs could be calculated from the sigmoidal concentration-effect
      curves. Furthermore, it was shown that drug treatment (10(-6) M CDA or 10(-6) M
      ARA-C) potentiated the apoptosis-inducing effects of irradiation (6 Gy) but not
      its necrosis-inducing potential. CONCLUSION: This study demonstrates that CDA,
      ARA-C, CDDP, and 5FU possess concentration-dependent apoptosis-inducing potential
      in the cell lines studied. The cytotoxic mechanism and cell-killing potential of
      these drugs is different, which is reflected by different EC50 and Emax values.
      Furthermore, a method for pharmacodynamic modeling is introduced that permits a
      quantitative approach for the assessment of the sensitivity of tumor cells to
      anticancer drugs and combined treatments.

PMID- 9619763
TI  - Phase I clinical and pharmacokinetic study of oral 9-aminocamptothecin (NSC
      603071).
AB  - PURPOSE: 9-Aminocamptothecin (9-AC) is a topoisomerase I inhibitor with high
      antitumor activity but poor solubility in conventional vehicles. The purpose of
      this study was to evaluate the toxicities and pharmacokinetics of a colloidal
      dispersion (CD) formulation of 9-AC when administered orally on a 5 days per week
      every 2 weeks schedule. METHOD: This formulation, which was developed for
      intravenous administration, was orally administered in 20 ml orange juice. A
      group of 16 cancer patients were treated at doses of 0.2-0.68 mg/m2 daily.
      RESULTS: Grade 1-2 nausea (n = 9) was common, usually occurring during the last 2
      days of dosing. No objective responses or cumulative toxicities were observed.
      Pharmacokinetic analysis of total 9-AC showed highly variable apparent oral 9-AC
      clearance and half-life. There was marked interpatient variability at each dose
      level in the 9-AC AUC and Cmax, and these parameters showed a poor correlation
      with dose (r2 = 0.07 and 0.38, respectively). CONCLUSIONS: We conclude that this
      formulation is not suitable for further clinical development because of poor
      bioavailability and highly variable and/or saturable absorption or elimination.
      Another formulation developed for oral administration is under study elsewhere.

PMID- 9619764
TI  - Determinant capture by MHC class II DR3 during processing of mycobacteria leprae
      65kD heat shock protein by human B cells.
AB  - Using T cell immunoblotting we have characterised the immunogenic fragments
      derived from the Mycobacteria Leprae 65kD heat shock protein that become
      associated with MHC class II DR3 during processing by a human B cell line. After
      5 h incubation with antigen, a peptide of approximately 12kD (approximately 110
      amino acids) was the only major fragment found associated with the class II MHC.
      The association of this oligopeptide was abolished if an excess of a synthetic
      peptide representing the minimal epitope was included in the culture or when
      cells were incubated at 4 degrees C. This suggests that the generation of this
      moiety is dependent on cell metabolism and that its binding to MHC is specific.
      This large fragment may represent an intermediate in the processing pathway,
      directly demonstrating the role of MHC in determinant capture during antigen
      degradation.

PMID- 9619765
TI  - Requirement for different presenting cells and for different processing
      mechanisms by human CD4 T helper clones specific for M. tuberculosis antigens.
AB  - Human T helper cells specific for mycobacterial antigens have been extensively
      investigated. Differences have been detected according to antigen specificity and
      to fine epitope specificity. In this work we have analyzed two additional
      parameters that allow discrimination among antigen specific T helper cells:
      requirement for certain types of antigen presenting cells (APC) and requirement
      for protease-sensitive antigen processing pathways. We used T cell clones from
      peripheral blood or from pleural exudates, and specific for different antigenic
      fractions of M. tuberculosis. APC were autologous peripheral blood mononuclear
      cells, adherent monocytes, adherent pleural monocytes, EBV transformed B
      lymphocytes and dendritic cells. Seven clones out of twelve were stimulated by
      all APC irrespective of their specificity, whereas other clones had more
      selective requirements. When protease inhibitors were used during antigen pulsing
      of APC, the production of certain epitopes, and thus T cell activation, was
      impaired with six clones out of sixteen. These results demonstrate that the human
      T helper repertoire specific for mycobacterial antigens is highly diverse also
      according to APC populations needed for presentation and to processing mechanisms
      required for production of the relevant T epitopes.

PMID- 9619766
TI  - Role of natural killer cells, macrophages, and accessory molecule interactions in
      the rejection of pig-to-primate xenografts beyond the hyperacute period.
AB  - Pig-to-primate cardiac xenografts surviving beyond the period of hyperacute
      rejection succumb after 3-4 days to a secondary immunologic response
      characterized by xenograft infiltration with NK cells and macrophages.
      Circulating baboon mononuclear cells contain NK cell precursors which mediate
      lysis of porcine endothelium by two distinct mechanisms: antibody-dependent
      cellular cytotoxicity and lymphokine activation. IL-2 activated NK lysis of
      porcine endothelium was 2.4-fold stronger than lysis occurring following
      engagement of FcRIII by xenoreactive IgG. IL-2 augmented NK lysis involved
      interactions between CD2 and CD49d on baboon NK cells and their respective
      ligands on porcine endothelium, since NK lysis was reduced either by using Mabs
      against CD2, CD49d, or porcine VCAM, or by treating endothelial cells with PIPLC
      to cleave GPI-linked molecules. These results imply that interactions between
      accessory molecule receptor-ligand pairs on primate NK cells, macrophages and
      porcine endothelium are of critical importance in delayed xenograft rejection.

PMID- 9619767
TI  - Relevant residues of DRbeta1 third hypervariable region contributing to the
      expression and to severity of rheumatoid arthritis (RA) in Mexicans.
AB  - Rheumatoid arthritis (RA) is a chronic autoimmune disease leading to destruction
      of the joints. Residues at positions 67-74 of the DRB1 third hypervariable region
      are involved in susceptibility (S) and resistance (P) to RA. DNA from 83 patients
      and 175 controls, all of them Mexican Mestizos were oligotyped using PCR-SSOP and
      PCR-SSP. The (S) alleles are DRB*0404 (p = 0.000004), *0401 (p = 0.007) and *1001
      (p = 0.008). Those associated with P are DRB1*0701 (p = 0.0001); *1101 (p =
      0.01); *1503 (p = 0.02); *0801 (p = 0.04); *1401 (p = 0.04).
      Susceptibility/protection are recessive traits; SS genotypes are increased in the
      patients (p = 0.0003) while PP genotypes are decreased in them (p = 0.00004). The
      motif at 67-74 and the valine or glycine at position 86 are relevant in the
      development and severity of RA in Mexicans. The associations suggest that
      residues 67, 70, 71 are central for susceptibility. The P alleles have D-70 or
      carry V-86 in the absence of D-70. Thus, susceptibility/protection depends on the
      combination of basic residues at these positions and a non-polar aa at 86
      contributes to resistance. Severity is also HLA influenced. DQA1*03011-DQB1*0302
      are associated to severe lesions in the presence of any DR4 subtype. Analyzing
      different ethnic groups is essential to elucidate the etiopathogenesis of RA.

PMID- 9619768
TI  - D6STNFa microsatellite locus correlates with CTLp frequency in unrelated bone
      marrow donor-recipient pairs.
AB  - The use of unrelated donors for bone marrow transplantation is associated with an
      increased morbidity and mortality when compared with HLA identical siblings,
      primarily due to an increased rate of graft-versus-host-disease. HLA matching for
      donors and recipients is the most important factor influencing the outcome of
      BMT. However, unrelated donor selection generally relies on matching only for HLA
      antigens without considering potential incompatibility for other MHC loci.
      Cellular assays have been developed to predict incompatibility that cannot be
      detected by current typing methods. The CTLp frequencies correlate with the
      degree of incompatibility of patient/donor and the clinical grade of GVHD. Since
      the CTLp assay is expensive and time consuming, an alternative is wanted. We
      studied the means of matching for microsatellites in determining MHC identity and
      possible correlation with CTLp frequencies. Therefore, 26 recipient/donor pairs
      were analysed for eleven microsatellite loci within and around the MHC region.
      Our study provides evidence that the D6STNFa locus correlates with CTLp
      frequency. The D6STNFa locus provides an additional marker that may help to
      improve the matching of unrelated donors and bone marrow recipients.

PMID- 9619769
TI  - HLA-G polymorphisms and allele frequencies in Caucasians.
AB  - HLA-G, a nonclassical class I MHC molecule, is uniquely expressed on extravillous
      cytotrophoblasts of the maternal-fetal interface and is suggested to be essential
      for establishment of maternal-fetal immune tolerance. Although the level of
      polymorphism in HLA-G has originally been considered low, number, nature and site
      of polymorphisms seem to vary between different ethnic populations. We
      investigated HLA-G polymorphisms in a population of German and Croatian origin by
      SSCP-analysis and direct sequencing as well as RFLP analysis for presence of the
      1597delC mutation. HLA-A alleles associated with the different HLA-G alleles were
      determined by SSP PCR-typing. In Caucasians, HLA-G exhibits a low degree of
      polymorphism on the amino-acid level and only slightly higher variability on the
      nucleotide level. In 264 independent chromosomes, 4 HLA-G alleles on the level of
      amino acid polymorphisms and an additional 6 variations of nucleotide sequences
      could be identified. The null-allele G*0105N was present at an allele frequency
      of 2.3%, which is higher than initially suggested for Caucasians but lower than
      in Hispanics and African-Americans. Furthermore, some HLA-G alleles exhibit
      strong linkage disequilibrium with HLA-A.

PMID- 9619770
TI  - Simultaneous HLA Class I and Class II antibodies screening with flow cytometry.
AB  - A flow cytometric method of simultaneously screening both HLA Class I and Class
      II panel reactive antibodies (PRA) was developed using a pool of 30 different
      Class I and 30 different Class II microbeads coated with purified HLA antigens.
      The antibodies in the serum that react specifically to the coated HLA antigens
      are detected by using a FITC-conjugated antibody against human IgG. Percent PRA
      can be determined by the percentage of microbeads that react positively to the
      serum. There is no cross-reactivity between the Class I and Class II microbeads.
      A mixture of Class I and Class II microbeads can be distinguished by their
      different fluorescent properties on the flow cytometry analysis. Thus, both Class
      I and Class II PRA can be detected from a single tube reaction.

PMID- 9619771
TI  - Nomenclature for Factors of the HLA System, Update February 1998. WHO
      Nomenclature Committee for Factors of the HLA System.

PMID- 9619772
TI  - Genetic vaccines: strategies for optimization.
AB  - Vaccination with attenuated or killed microbes, purified or recombinant subunit
      proteins and synthetic peptides is often hampered by toxicity, the presence of
      infectious agents, weak immune responses and prohibiting costs, especially in the
      developing world. Such problems may be circumvented by genetic immunization which
      has recently emerged as an attractive alternative to conventional vaccines.
      Numerous studies have already shown that immunization of experimental animals
      with plasmid DNA encoding antigens from a wide spectrum of bacteria, viruses,
      protozoa and cancers leads to protective humoral and cell-mediated immunity. This
      review deals with the background and progress made so far with DNA vaccines and
      their theoretical and practical advantages as well as potential risks, discusses
      proposed mechanisms of DNA transfection of cells and induction of immune
      responses to the produced vaccine antigen, and evaluates strategies for the
      control and optimization of such responses.

PMID- 9619773
TI  - Aerosol delivery of lipid:DNA complexes to lungs of rhesus monkeys.
AB  - PURPOSE: The potential use of aerosol delivery for non-viral gene therapy was
      tested by nebulization of lipid:DNA complexes to the lungs of rhesus monkeys.
      METHODS: Four female rhesus monkeys were dosed with lipid:DNA formulations via
      aerosol inhalation, where the DNA coded for the human Cystic Fibrosis
      Transmembrane Conductance Regulator (hCFTR) protein. Delivery of DNA was
      determined in lung samples by polymerase chain reaction (PCR) by qualitative and
      quantitative methods. Transgene specific messenger RNA was measured by reverse
      transcriptase PCR (RT-PCR) and protein expression and localization were evaluated
      by immunohistochemistry (IHC). RESULTS: Approximately four mg of DNA, complexed
      with cationic lipid 1.2-dimyristoyl-sn-glycero-3-ethylphosphatidylcholine (EDMPC)
      and cholesterol were delivered to the lungs of animals by airjet nebulizer. Three
      days after dosing, tissue samples from the lung were collected and shown to have
      vector specific DNA, RNA and the presence of CFFR protein. Specifically, the
      hCFTR protein was distributed widely, although non-uniformly, throughout airway
      epithelium being located on the apical surface of epithelial cells. Importantly,
      no adverse clinical effects were observed and the lungs showed no histological
      abnormalities or signs of acute inflammation. CONCLUSIONS: This study shows that
      lipid:DNA formulations based on EDMPC and cholesterol can be administered to
      primates by nebulization resulting in measurable expression of the hCFTR protein.
      The absence of inflammation is also encouraging and such systems may have utility
      for delivery of genes to the lungs for the treatment of a variety of pulmonary
      diseases including cystic fibrosis.

PMID- 9619774
TI  - In vitro myotoxicity of selected cationic macromolecules used in non-viral gene
      delivery.
AB  - PURPOSE: Cationic lipid/DNA complexes have been proposed as a method of in vivo
      gene delivery via intravenous or intramuscular injection. A concern with using
      these polycationic molecules is whether they are associated with tissue toxicity
      at the injection site. Therefore, the objective of these studies was to
      investigate the myotoxic potential of selected non-viral gene delivery
      macromolecules (e.g., cationic lipids and polymers) with and without plasmid DNA
      (pDNA) in vitro. METHODS: Myotoxicity was assessed by the cumulative release of
      creatine kinase (CK) over 90 minutes from the isolated rodent extensor digitorum
      longus muscle into a carbogenated balanced salt solution (BBS, pH 7.4, 37 degrees
      C) following a 15 microL injection of the test formulation. Phenytoin (Dilantin)
      and normal saline served as positive and negative controls, respectively.
      RESULTS: The myotoxicity of plasmid DNA (pDNA, approximately 5000bp, 1 mg/ml) was
      not statistically different from normal saline. However, the myotoxicity of
      Dilantin was 16-times higher than either normal saline or pDNA (p < 0.05).
      Cationic liposomes were found to be less myotoxic than polylysine and PAMAM
      dendrimers. Polylysine's myotoxicity was found to be dependent upon concentration
      and molecular weight. The myotoxicity of formulations of cationic liposomes(s),
      lower molecular weight polylysine (25,000) and higher concentration of PAMAM
      dendrimers with pDNA were found to be statistically less significant than those
      formulations without pDNA. CONCLUSIONS: The cationic liposomes were less myotoxic
      compared to the dendrimers and polylysine. Myotoxicity was dependent upon the
      type of cationic lipid macromolecule, concentration, molecular weight and the
      presence of pDNA. A possible explanation for this reduced tissue damage in
      cationic lipids complexed with pDNA is that the formation of complex reduces the
      overall positive charge of the injectable system resulting in less damage.

PMID- 9619775
TI  - Synergistic antitumor interaction of human monocyte chemotactant protein-1 gene
      transfer and modulator for tumor-infiltrating macrophages.
AB  - PURPOSE: In order to evaluate the possibility of synergistic antitumor gene
      therapy by the gene delivery of monocyte chemotactant protein-1 (MCP-1/MCAF/IE),
      the effect of a biological response modulater for macrophages on tumor
      progression of gene transfected tumor cells was studied. METHODS: Cachexia
      inducing adenocarcinoma cells (cell line colon 26, clone 20) were transfected
      with either a control plasmid or MCP-1 cDNA. RESULTS: The production of MCP-1
      reached 70-80 ng/ml in vitro when transfectant cells were cultured at a cell
      density of 1 x 10(5) cells/ml for 3 days. Transfection of MCP-1 cDNA did not
      affect the growth rate in vitro. Also, MCP-1-transfectants formed tumors after
      intra-footpad inoculation similar in size to the parental cells. The number of
      infiltrating macrophages in the primary tumor of the transfectant rapidly
      increased from the 3rd to 5th day after inoculation as revealed by
      immunohistochemical staining using an antibody against mouse macrophages. An
      earlier, greater, but no longer-lasting increase in tumor-infiltrating
      macrophages was induced in tumors by MCP-1 transfection was compared to that
      induced by the parent cells. On the 10th day after the inoculation, the tumor
      infiltrating macrophages in mice inoculated MCP-1 transfectants were decreased to
      a level similar to that of the parent cells. Groups of mice were treated
      intraperitoneally with LPS at different times after the inoculation. Tumor cells
      producing high levels of MCP-1 were significantly lysed by macrophages treated
      with LPS, whereas parental or control transfected cells were not. Conclusions.
      Combination immunotherapy can provide a rationale for the application of MCP-1
      treatment to increase immunological responses to cancer.

PMID- 9619776
TI  - Bootstrapping for pharmacokinetic models: visualization of predictive and
      parameter uncertainty.
AB  - PURPOSE: We explore use of "bootstrapping" methods to obtain a measure of
      reliability of predictions made in part from fits of individual drug level data
      with a pharmacokinetic (PK) model, and to help clarify parameter identifiability
      for such models. METHODS: Simulation studies use four sets (A-D) of drug
      concentration data obtained following a single oral dose. Each set is fit with a
      two compartment PK model, and the "bootstrap" is employed to examine the
      potential predictive variation in estimates of parameter sets. This yields an
      empirical distribution of plausible steady state (SS) drug concentration
      predictions that can be used to form a confidence interval for a prediction.
      RESULTS: A distinct, narrow confidence region in parameter space is identified
      for subjects A and B. The bootstrapped sets have a relatively large coefficient
      of variation (CV) (35-90% for A), yet the corresponding SS drug levels are
      tightly clustered (CVs only 2-9%). The results for C and D are dramatically
      different. The CVs for both the parameters and predicted drug levels are larger
      by a factor of 5 and more. The results reveal that the original data for C and D,
      but not A and B, can be represented by at least two different PK model
      manifestations, yet only one provides reliable predictions. CONCLUSIONS: The
      insights gained can facilitate making decisions about parameter identifiability.
      In particular, the results for C and D have important implications for the degree
      of implicit overparameterization that may exist in the PK model. In cases where
      the data support only a single model manifestation, the "bootstrap" method
      provides information needed to form a confidence interval for a prediction.

PMID- 9619777
TI  - Evaluation of various dissolution media for predicting in vivo performance of
      class I and II drugs.
AB  - PURPOSE: In this paper we seek to verify the differences in dissolution behavior
      between class I and class II drugs and to evaluate the suitability of two new
      physiologically based media, of Simulated Gastric Fluid (SGF) and of milk for
      their ability to forecast trends in the in vivo performance of class II compounds
      and their formulations. METHODS: Dissolution behavior of two class I drugs, i.e.
      acetaminophen and metoprolol, and of three class II drugs, i.e. danazol,
      mefenamic acid and ketoconazole, was studied with USP Apparatus 2 in water, SGF,
      milk, Simulated Intestinal Fluid without pancreatin (SIFsp) and in two media
      simulating the small intestinal contents in the fed (FeSSIF) and fasted (FaSSIF)
      states, respectively. RESULTS: Class I powders dissolved rapidly in all media
      tested. Acetaminophen dissolution in milk was slow from one tablet formulation,
      in all other cases dissolution was more than 85% complete in 15 minutes. The
      dissolution rate of metoprolol was shown to be dependent on formulation and
      manufacturing method, and one of the three tablet formulations did not meet
      compendial specifications (80%/30 minutes). Dissolution behavior of class II
      drugs was greatly affected by choice of medium. Dissolution from a capsule
      formulation of danazol proved to be dependent on the concentration of
      solubilizing agents, with a the 30-fold increase in percentage dissolved within
      90 minutes upon changing from aqueous media without surfactants to FaSSIF. Use of
      FeSSIF or milk as the dissolution medium resulted in an even greater increase in
      percentage dissolved, 100 and 180-fold respectively. Dissolution of the weak acid
      mefenamic acid from a capsule formulation is dependent on both pH and bile salt
      concentration, which leads to an offset between increased bile salt concentration
      and lower pH in the fed state compared to the fasted state medium. The weak base
      ketoconazole showed complete dissolution from a tablet formulation in Simulated
      Gastric Fluid without pepsin (SGFsp) within 30 minutes, 70% dissolution in 2
      hours under fed state simulated upper jejunal conditions but only 6% dissolution
      in 2 hours under fasted state conditions. CONCLUSIONS: As predicted, dissolution
      of class II drugs proved to be in general much more dependent on the medium than
      class I drugs. With the array of compendial and physiological media available, it
      should be possible to design a suitable set of tests to predict the in vivo
      dissolution of both class I and II drugs from immediate release formulations.

PMID- 9619778
TI  - Decreased expression and activity of P-glycoprotein in rat liver during acute
      inflammation.
AB  - PURPOSE: Drug disposition is often altered in inflammatory disease. Although the
      influence of inflammation on hepatic drug metabolism and protein binding has been
      well studied, its impact on drug transport has largely been overlooked. The
      multidrug resistance (MDR) gene product, P-glycoprotein (P-gp) is involved in the
      active secretion of a large variety of drugs. Our goal was to ascertain the
      influence of acute inflammation (AI) on the expression and functional activity of
      P-gp. METHODS: AI was induced in rats through turpentine or lipopolysaccharide
      (LPS) administration. Expression of P-gp in liver was detected at the level of
      protein on Western blots using the monoclonal antibody C-219 and at the level of
      mRNA using an RNase protection assay. P-gp mediated transport activity was
      assessed by measuring the verapamil-inhibitable efflux of rhodamine 123 (R123) in
      freshly isolated hepatocytes. RESULTS: Turpentine-induced AI significantly
      decreased the hepatic protein expression of P-gp isoforms by 50-70% and caused a
      significant 45-65% reduction in the P-gp mediated efflux of R123. Diminished mRNA
      levels of all three MDR isoforms were seen. LPS-induced AI similarly resulted in
      significantly reduced levels and activity of P-gp in liver. Although differences
      in the constitutive levels of P-gp were seen between male and female rats, the
      influence of AI on P-gp expression and activity was not gender specific.
      CONCLUSIONS: Experimentally-induced inflammation decreases the in vivo expression
      and activity of P-gp in liver. This is the first evidence that expression of P-gp
      is modulated in response to experimentally-induced inflammation.

PMID- 9619779
TI  - P-glycoprotein is more efficient at limiting uptake than inducing efflux of
      colchicine and vinblastine in HL-60 cells.
AB  - PURPOSE: To investigate the role of the P-glycoprotein (P-gp) drug efflux pump in
      the intracellular disposition of colchicine and vinblastine. METHODS: Uptake and
      efflux kinetics were studied in vitro in human lymphocytes and in HL-60 cells
      with or without the P-gp modulator, verapamil. RESULTS: In human lymphocytes,
      colchicine was slowly taken up (uptake half-life was 18.9+/-1.1 hr.) and
      verapamil increased colchicine uptake by 37%, whereas it did not modify
      colchicine efflux from cells. In HL-60 cells, colchicine uptake was non-linear
      and slower than that of vinblastine, the colchicine uptake half-life (11.1+/-0.5
      hr.) being 25-fold longer than that of vinblastine at 25 nM. Verapamil did not
      significantly modify colchicine uptake half-life, but increased its intracellular
      accumulation by 23% and that of vinblastine by 81%. Immuno-flow cytometry showed
      that P-gp expression in HL-60 cells increased significantly from 24 hr. following
      colchicine or vinblastine exposure. The significant increase in colchicine uptake
      induced by verapamil at 24 hr. was correlated with this enhanced P-gp expression.
      The drug efflux half-life was 11.5-fold higher for colchicine (23+/-0.9 hr) than
      vinblastine, indicating a much slower elimination of colchicine from cells that
      could be related to its longer dissociation half-life from the tubulin receptor.
      Verapamil treatment did not modulate either colchicine or vinblastine efflux
      kinetics, suggesting that the intracellular drugs are not available to the
      transmembrane P-gp binding sites. CONCLUSIONS: P-gp may not be the main reason
      for the slowness of colchicine uptake. It may be more efficient at controlling
      entry of colchicine and vinblastine through the plasma membrane than at mediating
      their efflux from HL-60 cells.

PMID- 9619780
TI  - Transport characteristics of peptidomimetics. Effect of the pyrrolinone
      bioisostere on transport across Caco-2 cell monolayers.
AB  - PURPOSE: To compare the permeation characteristics of amide bond-containing HIV-1
      protease inhibitors and their pyrrolinone-containing counterparts across Caco-2
      cell monolayers, a model of the intestinal mucosa. METHODS: Transepithelial
      transport and cellular uptake of three pairs of amide bond-containing and
      pyrrolinone-based peptidomimetics were assessed in the presence and absence of
      cyclosporin A using the Caco-2 cell culture model. The potential of the
      peptidomimetics to interact with biological membranes was estimated by IAM
      chromatography. RESULTS: In the absence of cyclosporin A, apical (AP) to
      basolateral (BL) flux of all compounds studied was less than the flux determined
      in the opposite direction (i.e., BL-to-AP). The ratio of the apparent
      permeability coefficients (Papp) calculated for the BL-to-AP and AP-to-BL
      transport (P(BL-->AP)/P(AP-->BL)) varied between 1.7 and 36.2. When individual
      pairs were ompared, P(BL-->AP)/P(AP-BL) ratios of the pyrrolinone-containing
      compounds were 1.5 to 11.5 times greater than those determined for the amide bond
      containing analogs. Addition of 25 microM cyclosporin A to the transport buffer
      reduced the P(BL-->AP)/P(AP-->BL) ratios for all protease inhibitors to a value
      close to unity. Under these conditions, the amide bond-containing peptidomimetics
      were at least 1.6 to 2.8 times more able to permeate Caco-2 cell monolayers than
      were the pyrrolinone-containing compounds. The intrinsic uptake characteristics
      into Caco-2 cells determined in the presence of 25 microM cyclosporin A were
      slightly greater for the amide bond-containing protease inhibitors than for the
      pyrrolinone-containing analogs. These uptake results are consistent with the
      transepithelial transport results determined across this in vitro model of the
      intestinal mucosa. CONCLUSIONS: The amide bond-containing and pyrrolinone-based
      peptidomimetics are substrates for apically polarized efflux systems present in
      Caco-2 cell monolayers. The intrinsic permeabilities of the amide bond-containing
      protease inhibitors are slightly greater than the intrinsic permeabilities of the
      pyrrolinone-based analogs through Caco-2 cell monolayers.

PMID- 9619781
TI  - Correlation between oral drug absorption in humans, and apparent drug
      permeability in TC-7 cells, a human epithelial intestinal cell line: comparison
      with the parental Caco-2 cell line.
AB  - PURPOSE: To determine and compare the relationship between in vivo oral
      absorption in humans and the apparent permeability coefficients (Papp) obtained
      in vitro on two human intestinal epithelial cell lines, the parental Caco-2 and
      the TC-7 clone. METHODS: Both cell lines were grown for 5-35 days on tissue
      culture-treated inserts. Cell monolayers were analysed for their morphology by
      transmission electron micrography, and for their integrity with respect to
      transepithelial electrical resistance, mannitol and PEG-4000 transport, and
      cyclosporin efflux. Papp were determined for 20 compounds exhibiting large
      differences in chemical structure, molecular weight, transport mechanisms, and
      percentage of absorption in humans. RESULTS: The TC-7 clone exhibits
      morphological characteristics similar to those of the parental Caco-2 cell line,
      concerning apical brush border, microvilli, tight junctions and polarisation of
      the cell line. The TC-7 clone however appeared more homogenous in terms of cell
      size. Both cell lines achieved a similar monolayer integrity towards mannitol and
      PEG-4000. Monolayer integrity was achieved earlier for the TC-7 clone, mainly due
      to its shorter doubling time, i.e. 26 versus 30 hours for parental Caco-2 cells.
      When using cyclosporin A as a P-glycoprotein substrate, active efflux was lower
      in the TC-7 clone than in the parental Caco-2 cells. The Papp and mechanisms of
      transport (paracellular or transcellular routes, passive diffusion and active
      transport) were determined for 20 drugs. A relationship was established between
      the in vivo oral absorption in humans and Papp values, allowing to determine a
      threshold value for Papp of 2 10(-6) cm/sec, above for which a 100% oral
      absorption could be expected in humans. Both correlation curves obtained with the
      two cell types, were almost completely superimposable. These studies also
      confirmed that the dipeptide transporter is underexpressed in both cell lines.
      CONCLUSIONS: On the basis of morphological parameters, biochemical activity and
      drug transport characteristics, the TC-7 clone appeared to be a valuable
      alternative to the use of parental Caco-2 cells for drug absorption studies.

PMID- 9619783
TI  - Towards the predictability of drug-lipid membrane interactions: the pH-dependent
      affinity of propanolol to phosphatidylinositol containing liposomes.
AB  - PURPOSE: Prediction of the pH-dependent affinity of (RS)-[3H]propranolol to mixed
      phosphatidylcholine (PhC)/phosphatidylinositol(Phl) membranes from the
      partitioning in the single lipid liposome/buffer systems. METHODS: Partition
      studies in liposome/buffer systems were performed by means of equilibrium
      dialysis at 37 degrees C between pH 2 and 11 at a molar propranolol to lipid
      ratio of 10(-6) to 10(-5) in the membrane. Results. The Phl membrane more
      strongly attracts the protonated (RS)-[3H]propranolol than the neutral solute,
      i.e. the partition coefficient of the protonated base (Pi) is 17'430+/-1320, P of
      the neutral compound (Pn) is 3110+/-1650. In the PhC-liposome system Pi is 580+/
      17, Pn 1860+/-20. The partition coefficients show an exponential dependence on
      the molar Phl fraction in mixed liposomes. The partitioning in mixed PhC/Phl
      membranes is predictable from Pn and Pi in the single lipid liposome systems.
      CONCLUSIONS: The negative charge of biological lipid membranes causes strong
      electrostatic interactions with positively charged solutes. This strong
      attraction is not predictable from the octanol/buffer partition system, but it is
      important regarding drug accumulation in the tissue and drug attraction by
      certain lipids in the vicinity of membrane proteins.

PMID- 9619782
TI  - Effects of fosfomycin and imipenem/cilastatin on nephrotoxicity and renal
      excretion of vancomycin in rats.
AB  - PURPOSE: The effects of fosfomycin and imipenem/cilastatin on the nephrotoxicity
      of vancomycin were studied in rats, and those on the renal handling of vancomycin
      were also investigated in perfused kidneys. METHODS: The protective effects of
      fosfomycin and imipenem/cilastatin on vancomycin nephrotoxicity were evaluated by
      increases in plasma concentration of creatinine and urea nitrogen in rats. The
      urinary excretion of vancomycin was measured and analyzed kinetically in the
      perfused rat kidney. RESULTS: The nephrotoxicity induced by vancomycin (500
      mg/kg, i.v.) was inhibited almost completely by co-administration of fosfomycin
      or imipenem/cilastatin. In the perfused rat kidney, the excretion ratio of
      vancomycin was less than those of p-aminohippurate and cimetidine, and greater
      than that of arbekacin, suggesting the secretion and reabsorption of vancomycin
      in renal tubules. The tissue/perfusate ratios of unbound vancomycin were not
      significantly changed by co-treatment with fosfomycin or imipenem/cilastatin.
      Imipenem/cilastatin significantly decreased the excretion ratio of vancomycin.
      Fosfomycin also decreased vancomycin excretion ratio, although this effect was
      not significant. CONCLUSIONS: The renal handling of vancomycin was different from
      those of organic anions and cations and an aminoglycoside antibiotic. The
      protective effects of fosfomycin and imipenem/cilastatin against the
      nephrotoxicity of vancomycin might be partly due to the change in renal handling
      of vancomycin, probably in its tubular secretion/ reabsorption, in rats.

PMID- 9619784
TI  - Solid lipid nanoparticles in lymph and plasma after duodenal administration to
      rats.
AB  - PURPOSE: To evaluate the uptake and transport of solid lipid nanoparticles (SLN),
      which have been proposed as alternative drug carriers, into the lymph and blood
      after duodenal administration in rats. METHODS: Single doses of two different
      concentrations of aqueous dispersions of unlabelled and labelled SLN (average
      diameter 80 nm) were administered intraduodenally to rats. At different times,
      samples of lymph were withdrawn by cannulating the thoracic duct and blood was
      sampled from the jugular vein. Monitoring continued for 45 and 180 minutes, for
      unlabelled and labelled SLN respectively. The biological samples were analysed by
      photon correlation spectroscopy (PCS), transmission electron microscopy (TEM) and
      gamma-counting. RESULTS: TEM analysis evidenced SLN in lymph and blood after
      duodenal administration to rats: the size of SLN in lymph did not change markedly
      compared to that before administration. The labelled SLN confirmed the presence
      of SLN in lymph and blood. CONCLUSIONS: The uptake and transport of SLN in the
      lymph, and to a lesser extent in the blood, were evidenced. The in vivo physical
      stability of SLN may have important implications in designing drug-carrying SLN.

PMID- 9619785
TI  - Influence of indocyanine green on plasma disappearance and biliary excretion of a
      synthetic thrombin inhibitor of the 3-amidinophenyl-alanine piperazide-type in
      rats.
AB  - PURPOSE: The pharmacokinetics of a number of synthetic peptidomimetic thrombin
      inhibitors is determined by extensive hepatic elimination. The objective was to
      further characterize the disposition in vivo of Pefa 1023, a novel 3
      amidinophenylalanine piperazide-type thrombin inhibitor, by influencing the
      hepatic handling with indocyanine green (ICG), which is actively taken up by the
      liver. METHODS: Pefa 1023 was administered intravenously to bile duct-cannulated
      rats, either alone or in combination with ICG. The concentrations of Pefa 1023 in
      blood plasma and bile were measured by a bioassay (thrombin clotting time),
      concentrations of indocyanine green were measured spectrophotometrically.
      RESULTS: ICG (10 mg/kg i.v. 15 min prior to or simultaneously with Pefa 1023)
      markedly influenced the plasma level and biliary excretion rate of the thrombin
      inhibitor Pefa 1023 given in a dose of 1 mg/kg i.v. The plasma level was more
      than twice that of the control, the maximum biliary excretion rate about one
      third and the fraction of dose excreted in bile about two thirds. CONCLUSIONS:
      The anionic dye ICG is able to interfere with the hepatic handling of a cationic,
      amidinophenylalanine piperazide-type thrombin inhibitor with the consequence of
      reduced hepatic clearance leading to higher plasma levels and lower biliary
      excretion of the latter.

PMID- 9619786
TI  - The quantitative analysis of crystallinity using FT-Raman spectroscopy.
AB  - PURPOSE: To establish if FT-Raman spectroscopy can be used to quantitate the
      degree of crystallinity in a model compound. METHODS: Mixtures containing
      different proportions of amorphous and crystalline indomethacin were prepared.
      Using the peak intensity ratio 1698 cm(-1) (crystalline) to 1680 cm(-1)
      (amorphous), a correlation curve was prepared. This correlation curve was
      validated by testing further samples of known composition. Partially crystalline
      indomethacin was prepared by milling crystalline indomethacin. RESULTS: A linear
      correlation curve was obtained across the entire range of 0-100% crystallinity.
      Using this method, it was possible to detect down to either 1% amorphous or
      crystalline content. The largest errors were found to result from inhomogeneities
      in the mixing of the calibration and validation samples. The spectra of the
      mechanically processed samples were similar to the spectra of the calibration
      samples, and the degree of crystallinity could be estimated in these samples.
      CONCLUSIONS: FT-Raman spectroscopy is a potentially useful method to complement
      existing techniques for the quantitative determination of crystallinity.

PMID- 9619787
TI  - A pragmatic test of a simple calorimetric method for determining the fragility of
      some amorphous pharmaceutical materials.
AB  - PURPOSE: To evaluate a simple calorimetric method for estimating the fragility of
      amorphous pharmaceutical materials from the width of the glass transition region.
      METHODS: The glass transition temperature regions of eleven amorphous
      pharmaceutical materials were characterized at six different heating and cooling
      rates by differential scanning calorimetry (DSC). RESULTS: Activation energies
      for structural relaxation (which are directly related to glass fragility) were
      estimated from the scan rate dependence of the glass transition temperature, and
      correlations between the glass transition widths and the activation energies were
      examined. The expected correlations were observed, and the exact nature of the
      relationship varied according to the type of material under consideration.
      CONCLUSIONS: The proposed method of determining the fragility of amorphous
      materials from the results of simple DSC experiments has some utility, although
      "calibration" of the method for each type of materials is necessary. Further work
      is required to establish the nature of the relationships for a broad range of
      amorphous pharmaceutical materials.

PMID- 9619788
TI  - Effect of spray drying and subsequent processing conditions on residual moisture
      content and physical/biochemical stability of protein inhalation powders.
AB  - PURPOSE: To understand the effect of spray drying and powder processing
      environments on the residual moisture content and aerosol performance of
      inhalation protein powders. Also, the long-term effect of storage conditions on
      the powder's physical and biochemical stability was presented. METHODS: Excipient
      free as well as mannitol-formulated powders of a humanized monoclonal antibody
      (anti-IgE) and recombinant human deoxyribonuclease (rhDNase) were prepared using
      a Buchi 190 model spray dryer. Residual moisture content and moisture uptake
      behavior of the powder were measured using thermal gravimetric analysis and
      gravimetric moisture sorption isotherm, respectively. Protein aggregation, the
      primary degradation product observed upon storage, was determined by size
      exclusion HPLC. Aerosol performance of the dry powders was evaluated after
      blending with lactose carriers using a multi-stage liquid impinger (MSLI).
      RESULTS: Spray-dried powders with a moisture level (approximately 3%) equivalent
      to the freeze-dried materials could only be achieved using high-temperature spray
      drying conditions, which were not favorable to large-male manufacturing, or
      subsequent vacuum drying. These dry powders would equilibrate with the subsequent
      processing and storage environments regardless of the manufacturing condition. As
      long as the relative humidity of air during processing and storage was lower than
      50%, powders maintained their aerosol performance (fine particle fraction).
      However, powders stored under drier conditions exhibited better long-term protein
      biochemical stability. CONCLUSIONS: Manufacturing, powder processing, and storage
      environments affected powder's residual moisture level in a reversible fashion.
      Therefore, the storage condition determined powder's overall stability, but
      residual moisture had a greater impact on protein chemical stability than on
      powder physical stability.

PMID- 9619789
TI  - Synthesis and physicochemical properties of lipophilic polyamide dendrimers.
AB  - PURPOSE: To synthesise symmetrical dendritic macromolecules with external lipid
      surfaces, to investigate their behaviour at the air-water interface and their
      ability to form supramolecular aggregates, and to gain an understanding of their
      potential as drug carriers. METHODS: Dendrimeric compounds were synthesised with
      molecular weights ranging from 737 (1st generation dendrimer) to 25,246 (6th
      generation dendrimer) with carbon numbers ranging from 40 to 1404. The surface
      behaviour of these compounds was determined using spread films at the air/water
      interface on a Langmuir trough, and transmission electron microscopy was used to
      study the supramolecular aggregates formed by the more hydrophobic members of the
      series. RESULTS: Dendrimers up to a maximum of 6 generations were synthesised.
      Surface saturation did not allow the completion of the synthesis of the 7th
      generation. The limiting surface areas at the air/water interface ranged from 0.4
      nm2 to 16.1 nm2 values in good agreement with the areas derived from computer
      generated molecular models (0.5 nm2 to 14 nm2). CONCLUSIONS: The synthesised
      dendrimers exhibited a linear relationship between area per molecule and the
      molecular weight of the compounds. A dendrimer with 16 lipoamino acid branches
      formed tubular supramolecular aggregates with a helical structure and dimensions
      in the long axis of 140-200 nm.

PMID- 9619790
TI  - Glow discharge plasma deposition (GDPD) technique for the local controlled
      delivery of hirudin from biomaterials.
AB  - PURPOSE: Biomaterials which release locally high concentrations of antithrombotic
      agents should lessen the thrombogenicity of the materials. To evaluate this
      approach, we prepared novel polyurethane matrices loaded with hirudin and coated
      them with 2-hydroxyethyl methacrylate (HEMA) by glow discharge plasma deposition
      (GDPD) to reduce the release rate. METHODS: Polyurethane (BioSpan) matrices
      containing hirudin and pore former (d-mannitol or BSA) were prepared by the
      solvent casting method. HEMA plasma deposition was then applied using GDPD
      technique to create a diffusional barrier film on the surface of the matrices.
      The effect of pore former and HEMA plasma coating on the release of hirudin was
      systematically investigated. Surface properties of matrices was also studied
      using Scanning Electron Microscopy (SEM) and Electron Spectroscopy for Chemical
      Analysis (ESCA). RESULTS: The release of hirudin from BioSpan matrix could be
      controlled by changing the weight fraction and particle size of pore former. HEMA
      plasma treatment of matrices produced a thin, highly cross-linked film on the
      surface. The initial burst and subsequent release of hirudin was significantly
      reduced after HEMA plasma coating, which suggested that the plasma disposition
      acted as a diffusional barrier and limited the release of hirudin incorporated in
      the polyurethane matrix. CONCLUSIONS: The plasma coating served as a diffusional
      barrier, and could work to control the release kinetics of hirudin by changing
      the various plasma coating conditions. Local delivery of hirudin using these
      biomaterials at the site of cardiovascular diseases can have the advantage of
      regional high levels of hirudin, as well as lowering systemic hirudin exposure,
      thereby minimizing the possibility of side effects.

PMID- 9619792
TI  - Physical aging of progesterone-loaded poly(D,L,-lactide-co-glycolide)
      microspheres.
AB  - PURPOSE: To study the interactions between a polymeric matrix and a drug during
      storage at a temperature lower than the glass transition temperature of the
      polymers. METHODS: Poly(lactide-co-glycolide) microspheres loaded with different
      progesterone ratios were stored at 4. 20 and 40 degrees C. DSC-scans were
      recorded at regular intervals, depending on the storage temperature. RESULTS: The
      physical aging of the polymeric matrix, as monitored by the amplitude of the
      endotherm associated with the glass transition, is slowed down by crystalline
      progesterone. The development of the progesterone polymorphic depends on the
      interface/volume ratio of the crystals. CONCLUSIONS: For polymeric drug delivery
      systems, the determination of all studies parameters must take into account an
      effect of dispersed drugs which are more sensitive as the storage temperature is
      lower than the glass transition temperature of the matrix.

PMID- 9619791
TI  - Monitoring microviscosity and microacidity of the albumin microenvironment inside
      degrading microparticles from poly(lactide-co-glycolide) (PLG) or ABA-triblock
      polymers containing hydrophobic poly(lactide-co-glycolide) A blocks and
      hydrophilic poly(ethyleneoxide) B blocks.
AB  - PURPOSE: The purpose of this study was to monitor the microenvironment of an
      encapsulated model protein during the release from biodegradable microparticles
      (MP) made from three different polymers, namely poly(lactide-co-glycolide) (PLG)
      and ABA-triblock polymers containing hydrophobic poly(lactide-co-glycolide) A
      blocks and hydrophilic poly(ethyleneoxide) B blocks with an A:B ratio of 90:10
      (ABA1O) and 70:30 (ABA30). METHODS: MP loaded with spin labeled albumin were
      prepared by a w/o/w technique. The particles were characterized by light
      scattering and electron microscopy. In vitro release of albumin was determined by
      size exclusion chromatography. Light microscopic experiments were conducted to
      visualize water penetration in the matrix. The protein microenvironment inside
      the degrading microparticles was characterized noninvasively by 2 GHz EPR
      spectroscopy. RESULTS: Water penetrated rapidly into all MP in the range of few
      minutes. A burst release was observed for PLG. The release from ABA block
      polymers continued for over 14 days despite the rapid solubilization of the
      protein inside the microparticles. The initial microviscosity of the protein
      environment inside the ABA particles after exposure to buffer was 2 mm2/s and
      increased with time. A gradual decrease of the pH to a value of 3.5 was observed
      within the MP. CONCLUSIONS: The data indicate that the microviscosity and
      microacidity inside protein loaded microparticles can be studied nondestructively
      by EPR spectroscopy. Our results clearly demonstrate that ABA-block polymers are
      superior to PLG allowing a controlled release of proteins from swollen
      microspheres.

PMID- 9619793
TI  - Partition behaviour of drugs in microemulsions measured by electrokinetic
      chromatography.

PMID- 9619794
TI  - Drug release from pH and ionic strength responsive poly(acrylic acid) grafted
      poly(vinylidenefluoride) membrane bags in vitro.

PMID- 9619795
TI  - Evaluation of the adhesion properties of salbutamol sulphate to inhaler
      materials.

PMID- 9619796
TI  - Induction-maintenance antiretroviral therapy: proof of concept.
AB  - OBJECTIVE: To investigate the concept of aggressive initial combination therapy
      followed by reduction to a less demanding maintenance regimen with respect to its
      potential for sustaining viral suppression. DESIGN: Durable viral suppression to
      < 20 HIV RNA copies/ml plasma was achieved with zidovudine-nevirapine-didanosine
      (ZDV-NVP-ddl) therapy. Potential for sustained antiviral response was explored
      for patients who began with ZDV-NVP-ddl and subsequently interrupted ddl.
      METHODS: Antiretroviral-naive patients were treated with ZDV-NVP, ZDV-ddl, or ZDV
      NVP-ddl. Viral load was measured with the Amplicor assay (limit of quantification
      400 copies/ml) and by the Ultra Direct assay (limit of quantification 20
      copies/ml) when the Amplicor result was < 500 copies/ml. Treatment adherence for
      each drug was recorded, including all dose adjustments. RESULTS: Five patients
      who had begun treatment with ZDV-NVP-ddl discontinued ddl for at least 6 weeks
      after achieving viral load levels below detection. All were documented to have
      sustained their viral load at < 20 copies/ml during the ddl interruption. Two
      patients permanently discontinued ddl, both with sustained viral load below
      detection for more than 1 year while treated with ZDV NVP. In contrast, no
      patient initially receiving ZDV-NVP was able to maintain viral load below
      detection for sustained periods; none had viral load below detection after week
      12 of treatment. CONCLUSIONS: After induction with ZDV-NVP-ddl, patients were
      able to sustain viral suppression with a regimen (ZDV NVP) that was only
      transiently effective as initial therapy. There was no evidence of virologic
      escape, even with the most sensitive measure of plasma viral load.

PMID- 9619797
TI  - Clinical and biological impact of antiretroviral therapy with protease inhibitors
      on HIV-related Kaposi's sarcoma.
AB  - OBJECTIVE: To evaluate the clinical and biological impact of protease inhibitors
      on HIV-associated Kaposi's sarcoma. DESIGN AND SETTING: A cohort of 10 patients
      included prospectively from April 1996 to June 1997 were studied in one
      institutional centre after initiation of protease inhibitors. PATIENTS AND
      METHODS: All patients but one (stable disease) had progressive Kaposi's sarcoma.
      Three out of 10 patients had stopped specific chemotherapy for Kaposi's sarcoma
      for more than 4 weeks, three were still under chemotherapy, and four had never
      received specific treatment of Kaposi's sarcoma. Plasma HIV viral load, human
      herpesvirus (HHV)-8 viraemia in peripheral blood mononuclear cells (PBMC), and
      CD4 cell count were sequentially assessed from the beginning of therapy. For six
      patients, a semiquantitative evaluation of HHV-8 viral load in the Kaposi's
      sarcoma lesions was performed during treatment using polymerase chain reaction.
      RESULTS: After initiation of HIV triple therapy with protease inhibitors, we
      observed six complete responses, two partial responses, and two patients with
      progressive disease. All patients had undetectable plasma HIV viral load within 2
      months of treatment. Undetectable HHV-8 viraemia in PBMC occurred in seven out of
      eight patients with partial or complete response and in none of the progressive
      patients. A decrease or negation of HHV-8 viral load in Kaposi's sarcoma lesions
      was observed in two complete responders. CONCLUSION: Our results suggest that
      antiviral therapy with protease inhibitors are clinically efficient in HIV
      associated Kaposi's sarcoma and that there exists a correlation between clinical
      response and negation of HHV-8 viraemia.

PMID- 9619799
TI  - The role of qualitative research in HIV/AIDS.

PMID- 9619798
TI  - A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in
      patients receiving HIV protease inhibitors.
AB  - OBJECTIVE: To describe a syndrome of peripheral lipodystrophy (fat wasting of the
      face, limbs and upper trunk), hyperlipidaemia and insulin resistance in patients
      receiving potent HIV protease inhibitor therapy. DESIGN: Cross-sectional study.
      SETTING: Outpatient clinic of a university teaching hospital. PATIENTS: HIV
      infected patients either receiving at least one protease inhibitor (n=116) or
      protease inhibitor-naive (n=32), and healthy men (n=47). INTERVENTIONS AND MAIN
      OUTCOME MEASURES: Lipodystrophy was assessed by physical examination and
      questionnaire and body composition by dual-energy X-ray absorptiometry. Fasting
      triglyceride, cholesterol, free fatty acid, glucose, insulin, C-peptide and
      fructosamine levels, other metabolic parameters, CD4 lymphocyte counts, and HIV
      RNA load were also assessed. RESULTS: HIV protease inhibitor-naive patients had
      similar body composition to healthy men. HIV protease inhibitor therapy was
      associated with substantially lower total body fat (13.2 versus 18.7 kg in
      protease inhibitor-naive patients; P=0.005), and significantly higher total
      cholesterol and triglyceride levels. Lipodystrophy was observed clinically in 74
      (64%) protease inhibitor recipients after a mean 13.9 months and 1(3%) protease
      inhibitor-naive patient (P=0.0001). Fat loss occurred in all regions except the
      abdomen after a median 10 months. Patients with lipodystrophy experienced a
      relative weight loss of 0.5 kg per month and had significantly higher
      triglyceride, cholesterol, insulin and C-peptide levels and were more insulin
      resistant than protease inhibitor recipients without lipodystrophy. Patients
      receiving ritonavir and saquinavir in combination had significantly lower body
      fat, higher lipids and shorter time to lipodystrophy than patients receiving
      indinavir. Three (2%) patients developed new or worsening diabetes mellitus.
      CONCLUSION: A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin
      resistance is a common complication of HIV protease inhibitors. Diabetes mellitus
      is relatively uncommon.

PMID- 9619800
TI  - Impact on the immune system of undetectable plasma HIV-1 RNA for more than 2
      years.
AB  - OBJECTIVE: To investigate the impact of prolonged HIV suppression on the immune
      system by analysing the expression of several lymphocyte surface markers in a
      group of HIV-1-infected patients who maintained undetectable HIV-1 RNA levels for
      more than 24 months. PATIENTS AND METHODS: The study included a highly selected
      group of nine HIV-1-infected asymptomatic subjects and seven HIV-1-seronegative
      controls. The inclusion criteria of HIV-1-infected patients was to have plasma
      HIV-1 RNA levels below 20 (1.3 log10) copies/ml for at least 24 months while
      under antiretroviral treatment with nucleoside analogues. The patient population
      was retrospectively taken from a cohort of 1418 treated subjects. Mean initial
      absolute CD4+ T-cell count and percentage were 468+/-234 x 10(6)/l (range, 202
      935 x 10(6)/l) and 25+/-6% (range, 16-33%), respectively. Plasma HIV-1 RNA
      quantification was determined using a standard and ultrasensitive reverse
      transcriptase polymerase chain reaction assay. Median HIV-1 RNA plasma level
      before antiretroviral treatment was 3.14 log10 copies/ml (range, 1.74-3.73 log10
      copies/ml). Two or three-colour immunophenotyping was performed on whole blood
      and frozen peripheral blood mononuclear cells by flow cytometry. RESULTS: A
      significant increase was noted in CD4+ lymphocyte counts at the end of the study
      in HIV-1-positive patients. In addition, the CD4: CD8 ratio rose significantly
      with respect to baseline, although it remained lower than in the controls.
      CD45RA+ and CD45RO+ population percentages did not differ between groups. A
      significant rise in CD45RA+ T cells was observed. Analysis of T-cell activation
      measuring the expression of human leukocyte antigen-DR and CD25 did not differ
      between groups. The proportion of CD8+ lymphocytes that were CD28+ was similar in
      both groups at the end of the follow-up. T-cell receptor Vbeta subfamily analysis
      showed that an expansion of the T-cell receptor repertoire might occur in these
      patients. CONCLUSION: Patients who maintain undetectable viral load for prolonged
      periods of time with antiretroviral therapy may achieve a partial immune
      restoration of the immune system. Our results suggest that treatment of patients
      at early stages of HIV infection is warranted.

PMID- 9619801
TI  - The M184V mutation in HIV-1 reverse transcriptase (RT) conferring lamivudine
      resistance does not result in broad cross-resistance to nucleoside analogue RT
      inhibitors.
AB  - OBJECTIVE: To investigate the prevalence and magnitude of M184V-mediated changes
      in susceptibility to zalcitabine, didanosine, stavudine and abacavir (1592U89
      succinate) in a cohort of lamivudine-treated patients. DESIGN AND METHODS: A
      total of 255 samples from patients treated with lamivudine and zidovudine with or
      without other nucleoside reverse transcriptase inhibitors (NRTI) were analysed
      for susceptibility to zidovudine, lamivudine, zalcitabine, didanosine and
      stavudine using a recombinant virus assay. Seventy-three samples originated from
      patients exposed to zidovudine and lamivudine only. A subset of 27 samples was
      investigated for cross-resistance to abacavir. Resistance was defined as a change
      in median inhibitory concentration more than fivefold compared with wild-type
      (high-level resistance, > 10-fold). A genotypic analysis of plasma-derived
      reverse transcriptase coding regions was carried out in samples with cross
      resistance. RESULTS: The majority of samples displayed wild-type or greater than
      wild-type sensitivity to zalcitabine, didanosine and stavudine: resistance was
      seen in 17.2, 9 and 6.3% of the total sample population, respectively. Of these,
      1.2, 2.7 and 2.4%, respectively, showed high-level resistance. The prevalence of
      resistance to a particular NRTI was lower in samples from patients not pretreated
      with that NRTI and in samples from patients exposed to zidovudine-lamivudine
      only. Cross-resistance was more prevalent in samples with high ZDV resistance.
      There was no obvious correlation between cross-resistance and genotype; all but
      two samples were mutant at codon 184. There were no consistent changes at
      positions associated with zidovudine resistance. The majority of samples from a
      subset (n=27) were four- to eightfold less sensitive to abacavir. There were no
      other genotypic changes in addition to M184V known to be associated with abacavir
      resistance. CONCLUSIONS: Cross-resistance was not commonly observed in this
      lamivudine-treated cohort. M184V per se is not expected to compromise subsequent
      treatment with NRTI such as didanosine-stavudine or combinations containing
      abacavir.

PMID- 9619802
TI  - Cytomegalovirus (CMV) strain differences between the eye and blood in AIDS
      patients with CMV retinitis.
AB  - OBJECTIVE: To investigate possible differences in cytomegalovirus (CMV) strain
      distribution between the eye and blood in AIDS patients with CMV retinitis.
      METHODS: CMV DNA sequences from aqueous humour and peripheral blood leukocytes
      (PBL), obtained from 13 AIDS patients with CMV retinitis, were compared. DNA was
      isolated and the CMV IE-1 sequence (part of the immediate early-1 gene) and the a
      sequence (located in the a-region) were amplified by polymerase chain reaction
      (PCR). The PCR products of the a-sequence were analysed by Southern blotting for
      amplified fragment-length polymorphisms. The level of divergence between the a
      sequences of aqueous humour- and PBL-derived CMV was studied in two patients by
      cloning these sequences followed by sequence analysis. RESULTS: CMV DNA could be
      detected in all aqueous humour samples and in 10 out of 13 paired blood samples.
      In the 10 patients, with CMV DNA detectable in both aqueous humour and PBL, seven
      cases showed differences between the amplified products of both compartments.
      Sequence analysis in two patients revealed that the aqueous humour and PBL of the
      same patient can harbour both identical, similar and highly divergent CMV a
      sequences. CONCLUSION: These results indicate that despite the haematogenous
      spread of CMV, the eye, being a relatively shielded organ, may contain CMV
      strains different from those found in the blood.

PMID- 9619803
TI  - HIV-1 DNA and mRNA concentrations are similar in peripheral blood monocytes and
      alveolar macrophages in HIV-1-infected individuals.
AB  - OBJECTIVE: To determine the relative contribution of alveolar macrophages,
      peripheral blood monocytes (PBM) and peripheral blood lymphocytes (PBL) from HIV
      infected individuals to HIV-1 viral load. METHODS: Alveolar macrophages were
      obtained by flexible bronchoscopy, and PBM and PBL by venipuncture from HIV-1
      infected individuals. Alveolar macrophages and PBM were purified using
      immunomagnetic bead selection to deplete CD3+ and CD19+ cells from
      bronchoalveolar lavage and peripheral blood mononuclear cells, respectively. DNA
      and mRNA were extracted and gag copy number quantified using polymerase chain
      reaction (PCR) and reverse transcriptase PCR. The titres of infectious cell
      associated HIV-1 in cells were determined by the endpoint dilution coculture
      technique for alveolar macrophages and PBM. RESULTS: Alveolar macrophages and PBM
      from HIV-1-infected subjects (n=11) contained equivalent concentrations of HIV-1
      DNA and HIV-1 mRNA as determined by PCR and reverse transcriptase PCR,
      respectively. Antiretroviral therapy was associated with reduced viral DNA
      concentrations in alveolar macrophages but not in PBM. PBL had a significantly
      higher level of proviral DNA and mRNA than alveolar macrophages or PBM.
      CONCLUSIONS: Although alveolar macrophages infected in vitro are more permissive
      for HIV-1 replication than PBM, this difference could not be demonstrated in
      vivo.

PMID- 9619804
TI  - MT-2 tropism and CCR-5 genotype strongly influence disease progression in HIV-1
      infected individuals.
AB  - BACKGROUND: The beta-chemokine receptor CCR-5 is the coreceptor for cellular
      entry by non-syncytium-inducing (NSI) HIV-1 strains that dominate early in
      infection. A 32 base-pair deletion (delta32) in the CCR-5 gene renders this
      coreceptor non-functional. Heterozygosity for this deletion [delta32/wild-type
      (wt)] is associated with slow disease progression. The purpose of this study was
      to document the combined impact on HIV-1 disease progression of the CCR-5
      genotype and the biological phenotype of HIV-1. METHODS: In a cross-sectional
      study of 258 HIV-1-infected Swedish individuals, the CCR-5 genotype (wt/wt or
      delta32/wt) was determined by polymerase chain reaction and the biological
      phenotype [NSI or syncytium-inducing (SI)] of virus isolates was determined in
      the MT-2 cell assay. Clinical status, HIV-1 RNA levels in plasma, CD4+ lymphocyte
      counts, and rate of CD4+ lymphocyte decline, based on retrospective analysis of
      CD4+ lymphocyte counts, were also recorded. None of the individuals were treated
      with protease inhibitors. RESULTS: The prevalence of the delta32/wt genotype was
      23%. Subjects with the delta32/wt CCR-5 genotype more often carried SI virus than
      subjects with the wt/wt genotype (49 versus 35%; P=0.067), but there were no
      differences between the two groups in prevalence of AIDS, viral load, CD4+
      lymphocyte count or CD4+ slope. NSI virus isolates were found in 159 (62%) out of
      258 individuals. Individuals with NSI had lower prevalence of AIDS (39 versus
      19%; P < 0.01), higher CD4+ lymphocyte counts (289+/-188 x 10(6)/l versus 153+/
      162 x 10(6)/l; P=0.001), lower viral loads (median, 4.45 log10 versus 4.91 log10
      copies/ml; P < 0.01) and a lower prevalence of the delta32/wt genotype (19 versus
      29%; P=0.067) compared with individuals with SI virus. When the material was
      further subdivided, subjects with the delta32/wt genotype and SI virus had the
      highest prevalence of AIDS (P < 0.001), lowest CD4+ lymphocyte count (P=0.0001)
      and highest viral load (P=0.023) whereas the opposite was true for subjects with
      the delta32/wt genotype and NSI virus. A significantly higher proportion of
      subjects with NSI virus with delta32/wt and wt/wt CCR-5 genotype had been
      immunized with recombinant gp160. CONCLUSION: In summary, the delta32/wt CCR-5
      genotype has a protective effect against HIV-1 disease progression that appears
      to be limited to individuals carrying HIV-1 variants with NSI phenotype.
      Immunization with recombinant gp160 tended to reduce the frequency of SI
      phenotypes.

PMID- 9619805
TI  - Neurological disorders during HIV-1 infection correlate with viral load in
      cerebrospinal fluid but not with virus phenotype.
AB  - OBJECTIVES: To verify the compartmentalization of HIV-1 within the central
      nervous system (CNS) and to define whether viral phenotype of HIV-1 isolates from
      cerebrospinal fluid (CSF) samples and CSF viral load correlate with the presence
      and type of neurological disorders. METHODS: A total of 33 HIV-1-infected
      patients with and without neurological disorders were included in the study. HIV
      1 isolation from paired CSF and peripheral blood mononuclear cell (PBMC) samples
      was attempted by a standard cocultivation technique; the biological phenotype of
      HIV-1 isolates was assessed by the MT-2 cell assay. CSF and plasma HIV-RNA levels
      were measured by a quantitative reverse transcripase-polymerase chain reaction.
      RESULTS: The rate of HIV-1 isolation from CSF and PBMC was 66% (22 isolates) and
      85% (28 isolates), respectively. Seventeen out of 22 (77%) CSF HIV-1 isolates
      were characterized as non-syncytium-inducing, and 15 out of 28 (68%) isolates
      from PBMC were typed as syncytium-inducing (SI). The presence of SI isolates in
      CSF was limited to patients with HIV-1-, cytomegalovirus- or JC virus-related
      disorders and was often associated with high levels of HIV-1 RNA in the CSF.
      DISCUSSION: Our results demonstrate a correlation between high levels of HIV RNA
      in CSF and the presence of neurological disorders thus indicating a possible role
      for HIV-1 RNA in the CSF as a biological marker of neurological disease. The
      finding of viruses with a different phenotype in paired CSF and PBMC indicates
      that HIV-1 may evolve differently in the brain and in the blood. This suggests
      compartmentalization of HIV-1 within the CNS.

PMID- 9619807
TI  - Influenza-like episodes in HIV-positive patients: the role of viral and
      'atypical' infections.
AB  - OBJECTIVES: To document viral and 'atypical' infections in HIV-positive patients
      and association with influenza-like symptoms. PATIENTS AND METHODS: Monthly
      culture of urine, faeces and throat swabs in 63 HIV-positive patients (30
      asymptomatic and 33 with AIDS-related complex/AIDS) over 5-27 months (with 1125
      patient-months of follow-up), with further sample collections during influenza
      like episodes. Standard viral detection methods were used. Throat swabs were
      assessed for Chlamydia sp. by culture and immunoblotting, and for Mycoplasma
      pneumoniae by polymerase chain reaction. RESULTS: Viruses were detected in 15
      (50%) and M. pneumoniae in nine (30%) out of 30 HIV-positive patients during an
      influenza-like illness. A close temporal relationship with symptoms was observed
      in 12 (40%) patients: cytomegalovirus in six (20%), M. pneumoniae in three (10%),
      herpes simplex virus in three (10%), and enterovirus in one (4%). Influenza-like
      symptoms were more frequent in asymptomatic HIV infection than in AIDS-related
      complex/AIDS patients (actuarial risk at 1 year, 63 versus 26%; P=0.002),
      particularly in those with CD4 cell counts >300 x 10(6)/l at enrolment (P=0.002).
      At least 44% (four out of nine) M. pneumoniae infections were asymptomatic and
      78% (seven out of nine) were associated with prolonged excretion (2-17 months).
      Chlamydia sp. were not detected. CONCLUSIONS: Influenza-like symptoms were more
      likely to be reported by HIV-positive patients at early stages of disease,
      possibly as a result of differences in immune responses to viral infection. There
      was a close association in 40% of cases between the development of symptoms and
      detection of cytomegalovirus, herpes simplex virus, enterovirus and M. pneumoniae
      (a previously unrecognized association).

PMID- 9619806
TI  - Discrepant responses to triple combination antiretroviral therapy in advanced HIV
      disease.
AB  - OBJECTIVES: To determine the clinical, virological and immunological outcome in a
      cohort of unselected patients receiving triple combination therapy for more than
      1 year. METHODS: Prospective follow-up of a cohort of 162 unselected, protease
      inhibitor-naive, antiretroviral-experienced patients with advanced HIV disease,
      treated with indinavir combined with two nucleoside analogues. RESULTS: The mean
      CD4 cell count and plasma HIV RNA level in the study group at baseline were 69+/
      5 x 10(6)/l and 4.75+/-0.07 log10 copies/ml, respectively. Five per cent of
      patients died prematurely or were lost to follow-up. Fifty-seven per cent of
      patients responded to therapy, as assessed by a sustained increase in CD4 cell
      counts above 50 x 10(6)/l and a decrease in plasma HIV RNA greater than 1 log10
      copies/ml, throughout 12.1 months of follow-up. Seventeen per cent of patients
      were immunological and virological non-responders. Twenty-one per cent of
      patients exhibited discrepant virological and immunological responses to
      treatment, of whom one-half failed to exhibit significant increases in CD4 cells
      despite a virological response to therapy and one-half exhibited increased CD4
      cell counts in the absence of significant decrease in plasma viral load. The
      incidence of AIDS-defining events in the latter group of patients was similar to
      that of responder patients, whereas their incidence was higher in patients who
      failed to exhibit a virological and immunological response and those who failed
      to increase CD4 cells despite a significant decrease in viral load. CONCLUSION:
      Our observations of discrepant immunological and virological responses to
      treatment raise the issue of the significance of persistent elevated levels of
      plasma HIV RNA and of the relevance of measurements of plasma viral load for
      assessing the efficacy of antiretroviral therapy in patients whose CD4 cell
      counts increase despite the absence of significant decrease in plasma HIV viral
      load.

PMID- 9619808
TI  - Incubation period of HIV-1 in perinatally infected children. New York City
      Perinatal HIV Transmission Collaborative Study Group.
AB  - OBJECTIVES: To estimate the distribution of the incubation period of HIV-1 among
      perinatally infected children and to test the hypothesis that this distribution
      has been changing over time. DESIGN: An analysis of 190 perinatally HIV-1
      infected children born between 1986 and 1997 in eight medical centers in New York
      City to women enrolled in a prospective cohort study. METHODS: Non-parametric
      Kaplan-Meier method and parametric survival analysis. RESULTS: Using the Kaplan
      Meier method it was estimated that among perinatally HIV-1-infected children, 48%
      [95% confidence interval (CI), 41-56] developed AIDS by 3 years of age after
      which the rate was less than 3% per year. Using a parametric survival analysis
      for extrapolation, it was predicted that 33% (95% CI, 23-43) would remain AIDS
      free at 13 years of age. Median age at onset of AIDS was estimated to be 4.1
      years (95% CI, 1.9-6.4) by parametric survival analysis. The year of birth was
      significantly associated with AIDS-free survival, suggesting an increase in the
      time to AIDS over the years. This association remained significant (P=0.03) after
      adjustment for those maternal characteristics that have also changed over time:
      timing of enrollment (prepartum versus postpartum), zidovudine, alcohol, and hard
      drug (heroin, cocaine or methadone) use during pregnancy. CONCLUSIONS: Although a
      substantial proportion of perinatally HIV-1-infected children develop AIDS very
      early in life, a significant and increasing percentage of them are expected to
      survive into adolescence without developing AIDS. Further research is needed to
      determine the factors associated with the lengthening survival to AIDS.

PMID- 9619809
TI  - Mucosal disruption due to use of a widely-distributed commercial vaginal product:
      potential to facilitate HIV transmission.
AB  - OBJECTIVE: Policresulen vaginal suppositories are a condensation product of
      metacresolsulfonic acid and formaldehyde. We investigated their use by female
      commercial sex workers (CSW) and whether such use could facilitate HIV
      transmission. METHODS: We interviewed female CSW in Thailand about use of the
      product, and we directly observed the effects of self-administration of a single
      suppository by each of six women. RESULTS: Of 200 CSW interviewed, 32% had used
      policresulen vaginal suppositories in the preceding year and 46% had used them at
      some time. Many used them for reasons not listed on the package insert, such as
      improving their male partners' sexual pleasure, and most did not abstain from
      vaginal sex following use. Among 36 brothel-based and 67 non-brothel-based CSW
      with known HIV infection, the use of the product was not associated with HIV-1
      infection (adjusted relative risk 1.0, 95% confidence interval, 0.5-2.0).
      Exfoliation of the vaginal and cervical mucosa was observed in all six CSW 1 day
      after product use, and, although it could have been the result of repeated
      examinations, an increase in genital HIV-1 RNA shedding was also detected in all
      three HIV-seropositive women. CONCLUSION: Although there was no epidemiological
      association with HIV infection, policresulen vaginal suppository use did disrupt
      the genital mucosa and therefore may have the potential to facilitate HIV
      transmission. Drug licensing authorities may wish to reassess the safety of this
      product. If the product continues to be distributed, steps should be taken to
      limit its use to the specific conditions for which it is indicated and to ensure
      that women abstain from vaginal sex following its use.

PMID- 9619810
TI  - Demographic impact of the HIV epidemic in Thailand.
AB  - OBJECTIVE: To assess the impact of the HIV epidemic on the demographic
      development of the Thai population. METHODS: A deterministic mathematical model
      was used to predict simultaneously epidemiological and demographic processes.
      Partial differential equations express the relationships between biological,
      behavioural and demographic variables. The model allows the evaluation of
      different sexual mixing patterns, variable transmission probabilities and
      incubation times. Validity analysis was performed by generating antecedent HIV
      prevalence patterns among military recruits and pregnant women. RESULTS: On the
      national level in Thailand we predict that the cumulative number of people in
      Thailand with HIV infection will exceed 1 million by 1999; the number of deaths
      from AIDS will be 555000 by the year 2000 but will not reach 1 million until
      after the year 2014. Without the HIV epidemic the population growth rate was
      estimated at 1.3% per annum until 1995, after which a decline to 0.9% by 2005 is
      predicted. The HIV epidemic started to affect the population growth rate by
      0.026% per year in 1991, and the difference is predicted to rise to about 0.12%
      per year during the period 1995-2000, to decline to 0.06% in 2005 and then to
      disappear. In the mid-1990s HIV affected mainly the 15-35-year-old age group, but
      over time younger and older age groups have been affected as a result of
      perinatal transmission, and a decline in fertility as well as ageing of the 15-35
      year-old birth cohort. Because of HIV, in 2000 there will be 612000 (1%) fewer
      people than expected and by 2010, 1140000 fewer (1.6%). We predict that the
      demographic impact of the HIV epidemic in the northern region will follow the
      same pattern, but with greater severity. Here, the effect on the population
      growth rate and the population age distribution is likely to be twice as high as
      at the national level. CONCLUSIONS: It is estimated that 1 million Thais will be
      infected with HIV by the year 2000 and an almost equal number will have died of
      AIDS by the year 2014. Although these numbers seem high, their direct and
      indirect effects on the demographic structure of the Thai population are small.
      However, at a regional level, for example in the northern region, the effect of
      the HIV epidemic may be more severe.

PMID- 9619811
TI  - Readiness of high-risk populations in the HIV Network for Prevention Trials to
      participate in HIV vaccine efficacy trials in the United States.
AB  - OBJECTIVE: To determine the willingness of populations at high risk of HIV-1
      infection to participate in HIV vaccine efficacy trials, determine factors
      influencing decision-making, and evaluate knowledge levels of vaccine trial
      concepts. DESIGN: Cross-sectional study. METHODS: HIV-1-negative homosexual men,
      male and female injecting drug users and non-injecting women at heterosexual risk
      were recruited in eight cities in the United States (n=4892). RESULTS: A
      substantial proportion of the study population (77%) would definitely (27%) or
      probably (50%) be willing to participate in a randomized vaccine efficacy trial.
      Increased willingness was associated with high-risk behaviors, lower education
      level, being uninsured or covered by public insurance, and not having been in a
      previous vaccine preparedness study. Altruism and a desire for protection from
      the vaccine were major motivators for participation. Major concerns included
      positive HIV-1 antibody test due to vaccine, safety of the vaccine, and possible
      problems with insurance or foreign travel. Baseline knowledge of vaccine trial
      concepts was low. CONCLUSIONS: It is likely that high-risk volunteers will be
      willing to enroll in HIV vaccine efficacy trials. A variety of participant and
      community educational strategies are needed to address participant concerns, and
      to ensure understanding of key concepts prior to giving consent for
      participation.

PMID- 9619812
TI  - Determinants of delayed diagnosis of HIV infection in France, 1993-1995.
AB  - OBJECTIVE: To describe the circumstances of the first HIV-positive test and to
      study the determinants of a delayed diagnosis of HIV infection. METHODS: In a
      retrospective study among adult AIDS patients diagnosed between July 1993 and May
      1995 in two French districts, data on socioeconomic characteristics,
      circumstances of first HIV-positive test and attitudes and behaviours regarding
      medical care were collected in a confidential interview and analysed for
      potential association with a late test, defined as a first HIV-positive test
      within 6 months of AIDS diagnosis. RESULTS: Of the 359 AIDS patients studied, 69
      (19.2%) had a late test. Late testers were more likely than other patients to
      have had an HIV-positive test because of clinical symptoms (89.7 versus 38.9%, P
      < 0.001) and not to perceive themselves as being at risk of infection with HIV
      (53.6 versus 39.3%, P < 0.05). The proportion of late testers was 34.6% among
      heterosexually infected patients, 12.7% among homo-/ bisexual men and 9.6% among
      injecting drug users. Factors independently associated with a late test were male
      gender [adjusted odds ratio (aOR), 5.6; 95% confidence interval (CI), 1.7-18.9]
      and absence of earned income (aOR, 5.2; 95% CI, 1.4-19) among heterosexually
      infected patients; high education (aOR, 3.1; 95% CI, 1.0-9.6) and having
      consulted a person practising alternative medicine (aOR, 3.4; 95% CI, 1.2-10) in
      homo-/bisexual men. CONCLUSIONS: Despite incentives to be tested for HIV, many
      individuals in France are still tested too late, even if they are in known high
      risk groups. Efforts to test HIV-infected people as early as possible should be
      made by increasing the perception of HIV risk and decreasing the level of missed
      opportunities for testing. Current case management approaches make this
      recommendation critically important from both public health and an individual
      perspective.

PMID- 9619813
TI  - Modelling the spread of HIV in social networks of injecting drug users.
AB  - OBJECTIVE: To explore the risk of a future rise of HIV prevalence in populations
      of injecting drug users (IDU) with low HIV prevalence but continuing risk
      behaviour, and to study the potential influence of prevention measures on HIV
      incidence. METHODS: A stochastic simulation model was used to describe a network
      of long-term buddy relationships in a population of IDU. HIV transmission took
      place when borrowing injecting equipment from an infected buddy or stranger. The
      probability of transmission depended on the duration of infection. Individuals
      remained in the population on average for 10 years. Two surveys amongst IDU in
      The Netherlands containing information about risk behaviour were used to estimate
      model parameters. We investigated the effect of different prevention strategies.
      RESULTS: Below a threshold sharing frequency the epidemic never takes off; above
      the threshold there is a large stochastic variation in prevalence. After
      reduction of risk behaviour, HIV prevalence decreases very slowly. Reducing
      sharing with strangers is more effective than reducing the overall sharing
      frequency. Prevention focused on new IDU greatly reduces HIV incidence. Reduction
      of sharing frequency in HIV-positive IDU has no significant influence on HIV
      incidence at HIV testing rates of 10 and 50% per year, if infectivity is highest
      during primary infection. CONCLUSIONS: A stabilization of HIV prevalence does not
      exclude the possibility of a future rise. Predictions about the future course of
      an epidemic are inherently uncertain. The effect of prevention programmes on HIV
      prevalence only becomes visible on a long time-scale. Social networks of IDU play
      an important role in transmission dynamics and success of prevention.

PMID- 9619814
TI  - The demographic impact of the HIV epidemic in Thailand.

PMID- 9619815
TI  - Co-trimoxazole administered for Pneumocystis carinii pneumonia prophylaxis does
      not interfere with saquinavir pharmacokinetics.

PMID- 9619816
TI  - Emergence of a ganciclovir-resistant human cytomegalovirus strain with a new UL97
      mutation in an AIDS patient.

PMID- 9619817
TI  - HIV-1 RNA levels in cerebrospinal fluid and plasma correlate with AIDS dementia.

PMID- 9619819
TI  - Heterosexual transmission of HIV in men and women in a Scottish cohort.

PMID- 9619818
TI  - Inhibition of interleukin-2 and interferon-gamma by an HIV-1 Nef-encoded
      synthetic peptide.

PMID- 9619820
TI  - Persistence of HIV-1 variants harbouring the zidovudine resistance mutation at
      pol codon 215 in patients who respond to triple combination therapy.

PMID- 9619821
TI  - Influence of indinavir and ritonavir on warfarin anticoagulant activity.

PMID- 9619822
TI  - HIV-1 in the female genital tract and the effect of antiretroviral therapy.

PMID- 9619823
TI  - Severe anoxic hepatic necrosis in an HIV-1-hepatitis C virus-co-infected patient
      starting antiretroviral triple combination therapy.

PMID- 9619824
TI  - Antiretroviral triple therapy decreases HIV viral load but does not alter
      hepatitis C virus (HCV) serum levels in HIV-HCV-co-infected haemophiliacs.

PMID- 9619825
TI  - Phosphorylation of bovine leukemia virus Tax protein is required for in vitro
      transformation but not for transactivation.
AB  - The Tax proteins of the oncovirinae viruses are phosphorylated transcriptional
      activators that exhibit oncogenic potential. The role of phosphorylation in their
      functional activities remains unknown. As a model for the Human T-cell leukemia
      virus type I (HTLV-I), Bovine Leukemia Virus (BLV) permits the characterization
      of viral replication and leukemogenesis in vivo. Here, we show that the BLV Tax
      protein is phosphorylated on serine residues 106 and 293 both in insect and in
      mammalian cells. These sites can also be efficiently phosphorylated by the cdc2
      and MAP kinases in vitro. Mutation of these residues does not affect the capacity
      of the Tax protein to function as a transactivator. Indeed, the Tax proteins
      mutated at one or both serines increase LTR-directed viral transcription at
      levels similar to those obtained with wild-type Tax in cell culture. Moreover,
      inhibition of Tax phosphorylation by W7, a calmodulin antagonist, does not alter
      its transactivation activity. Thus, phosphorylation on serines 106 and 293 is not
      required for transactivation by Tax. However, simultaneous substitution of both
      serines into alanine residues destroys the capacity of Tax to cooperate with the
      Ha-ras oncogene to transform primary rat embryo fibroblasts and induce tumors in
      nude mice. When the serines were replaced with aspartic acid residues, the
      oncogenic potential of Tax was maintained indicating that the negative charge
      rather than the phosphate group itself was required for Tax oncogenicity.
      Finally, to assess the role of the serine residues in vivo, recombinant viruses
      which express the Tax mutants were constructed and injected into sheep. It
      appeared that the mutated proviruses replicate at levels similar to the wild-type
      virus in vivo. We conclude that Tax phosphorylation is dispensable for
      transactivation and viral replication in vivo but is required for its oncogenic
      potential in vitro.

PMID- 9619826
TI  - Potential role for cathepsin D in p53-dependent tumor suppression and
      chemosensitivity.
AB  - Cathepsin D (CD), the major intracellular aspartyl protease, is a mediator of IFN
      gamma and TNF-alpha induced apoptosis. Using subtractive hybridization screening
      we isolated CD as an upregulated transcript in PA1 human ovarian cancer cells
      undergoing adriamycin-induced apoptosis. CD mRNA levels increased in wild-type
      p53-expressing PA1, ML1 leukemia and U1752 lung cancer cells but not in mutant
      p53-expressing cells following adriamycin exposure. Overexpression of CD
      inhibited growth of colon, liver, and ovarian cancer cells. CD protein expression
      was increased by exposure of ML1 cells to etoposide, adriamycin or gamma
      radiation. Inhibition of CD protease with Pepstatin A suppressed p53-dependent
      apoptosis in lymphoid cells, suggesting a possible role for CD in p53-dependent
      cell death. CD-/- fibroblasts were found to be more resistant to killing by
      adriamycin and etoposide, as compared to CD+/+ cells. Two p53 DNA-binding sites
      located in the CD-promoter specifically bound to p53 protein in vitro and
      appeared to mediate transactivation of a CD-promoter luciferase-reporter during
      p53-dependent apoptosis. These observations link CD protease to p53-dependent
      tumor suppression and chemosensitivity.

PMID- 9619827
TI  - Src can regulate carboxy terminal interactions with AFAP-110, which influence
      self-association, cell localization and actin filament integrity.
AB  - The SH2 and SH3 binding partner AFAP-110 is a tyrosine phosphorylated substrate
      of Src. AFAP-110 has been hypothesized to link Src to actin filaments, which may
      contribute to the effects of Src upon actin filament integrity. However, it has
      been unclear what effect activated Src (Src527F) has upon AFAP-110 structure or
      function and whether AFAP-110 plays a role in actin filament integrity. We report
      here that the carboxy terminal 127 amino acids of AFAP-110 are comprised of an
      alpha-helical region that contains a leucine zipper motif. This indicated the
      potential of AFAP-110 to self-associate. Expression of the carboxy terminus as a
      fusion protein (GST-cterm) will permit affinity absorption of cellular AFAP-110.
      The integrity of the alpha-helical leucine zipper motif in GST-cterm is required
      for affinity absorption, but binding is not due to a classical leucine zipper
      interaction. Co-expression of Src527F, unlike cSrc, will abrogate affinity
      absorption of AFAP-110 with GST-cterm. These data indicate that Src527F has
      affected a change in the carboxy terminal structure that renders AFAP-110
      unavailable for affinity absorption. Superose chromatography demonstrate that
      AFAP-110 will fractionate as a monomer or multimer, indicating AFAP-110 can be
      detected in a self-associated form in cell lysates. Co-expression of Src527F
      resulted in AFAP-110 fractionating with a molecular weight that predicts only a
      multimeric population. Deletional mutagenesis also indicate a biological role for
      the carboxy terminus in cellular localization and actin filament integrity.
      Deletion of the entire carboxy terminal alpha-helix (84 amino acids) will not
      permit AFAP-110 to efficiently colocalize with actin filaments or the cell
      membrane. Deletion of only the leucine zipper region of the carboxy terminal
      alpha-helix (44 amino acids) from AFAP-110 (AFAPAdeltazip) demonstrate that both
      AFAPdeltalzip and actin filaments are repositioned into rosette-like structures,
      similar to the effects of Src527F, while co-expression of AFAP-110 with cSrc will
      not affect actin filaments. These data indicate that AFAP-110 can play an
      important role in modulating actin filament integrity through carboxy terminal
      interactions that can be affected by Src527F.

PMID- 9619828
TI  - A role of the tuberous sclerosis gene-2 product during neuronal differentiation.
AB  - Tuberous sclerosis is an autosomal dominant disorder. Besides the development of
      benign growths (hamartomas) in different tissues, one hallmark of this disease is
      the presence of highly epileptogenic dysplastic lesions in the cerebral cortex
      (tubers) composed of abnormal shaped neurones. Patients often show evidence of
      severe mental retardation. Linkage analysis revealed two disease-determining
      genes on chromosome 9 and chromosome 16. The TSC2 gene on chromosome 16 encodes a
      1784-amino acid putative tumour suppressor protein, tuberin, that functions as a
      GTPase-activating protein. Here we show that tuberin expression is upregulated
      upon induction of neuronal differentiation in the neuroblastoma cell lines SK-N
      SH and LAN-1. This upregulation occurs at post-transcriptional level and is
      independent of the proliferation status. TSC2 expression is unaffected during
      differentiation of C2C12 myoblasts into myotubes and of F9 embryonal carcinoma
      cells into cells resembling parietal endoderm. Antisense inhibition of tuberin
      expression in SK-N-SH or LAN-1 cells inhibits neuronal differentiation, but does
      not affect the differentiation of F9 cells. Ectopic overexpression of TSC2 not
      only reverts the antisense-associated phenotype but furthermore accelerates the
      neuronal differentiation process. Our data show for the first time that tuberin
      plays a critical role in neuronal differentiation. Such role is consistent with
      the phenotype of tuberous sclerosis patients, who inherit one defective TSC2
      allele, and frequently lose the remaining normal allele in many of the
      tubers/hamartomas which develop in the central nervous system of these patients.

PMID- 9619829
TI  - XPA-deficiency in hairless mice causes a shift in skin tumor types and mutational
      target genes after exposure to low doses of U.V.B.
AB  - Xeroderma pigmentosum (XP) patients with a defect in the nucleotide excision
      repair gene XPA, develop tumors with a high frequency on sun-exposed areas of the
      skin. Here we describe that hairless XPA-deficient mice also develop skin tumors
      with a short latency time and a 100% prevalence after daily exposure to low doses
      of U.V.B. Surprisingly and in contrast to U.V.B.-exposed repair proficient
      hairless mice who mainly develop squamous cell carcinomas, the XPA-deficient mice
      developed papillomas with a high frequency (31%) at a U.V. dose of 32 J/m2 daily.
      At the highest daily dose of 80 J/m2 mainly squamous cell carcinomas (56%) and
      only 10% of papillomas were found in XPA-deficient hairless mice. p53 gene
      mutations were examined in exons 5, 7 and 8 and were detected in only 3 out of 37
      of these skin tumors, whereas in tumors of control U.V.B.-irradiated wild type
      littermates this frequency was higher (45%) and more in line with our previous
      data. Strikingly, a high incidence of activating ras gene mutations were observed
      in U.V.B.-induced papillomas (in 11 out of 14 tumors analysed). In only two out
      of 14 squamous cell carcinomas we found similar ras gene mutations. The observed
      shift from squamous cell carcinomas in wild type hairless mice to papillomas in
      XPA-deficient hairless mice, and a corresponding shift in mutated cancer genes in
      these tumors, provide new clues on the pathogenesis of chemically- versus U.V.B.
      induced skin carcinogenesis.

PMID- 9619830
TI  - Prognostic significance of allelic losses in primary melanoma.
AB  - Loss of genetic material, including loss of loci on chromosome arms 6q, 9p, and
      10q, occurs frequently in cutaneous melanoma but infrequently in benign
      melanocytic nevi or other melanocytic lesions, suggesting that these genetic
      alterations are important in the development and progression of melanoma. To
      examine whether allelic loss is of prognostic importance in melanoma, disease
      free survival was related to loss of heterozygosity on 6q, 9p and 10q in 83
      individuals with sporadic primary cutaneous melanoma. Loss of chromosome arms 6q
      and 10q were each significantly associated with a poorer clinical outcome
      (P=0.013 and P=0.001 respectively). In a subgroup of 41 subjects whose primary
      tumours were allelotyped, the fractional allelic loss (FAL) at 39 autosomal arms
      also significantly correlated with disease-free survival (P=0.013), with an
      increase in FAL associated with a poorer outcome; this association remained
      significant when controlled for tumour thickness (P=0.035). In addition, a
      greater proportion of cells were immunopositive for Ki67 antigen, p53 and p21WAF1
      protein in the primary melanomas than in the benign melanocytic nevi, however,
      only p53 over-expression was significantly associated with improved survival
      (P=0.041).

PMID- 9619831
TI  - Gastrin induces phosphorylation of eIF4E binding protein 1 and translation
      initiation of ornithine decarboxylase mRNA.
AB  - Gastrin via its G-protein coupled specific receptor induces transcription of c
      fos and c-jun genes through a ras-MAPK pathway. Ornithine Decarboxylase (ODC), a
      growth regulated proto-oncogene, was chosen to investigate gastrin effects on
      translation initiation of mRNAs exhibiting a 5'UnTranslated Region (5'UTR)
      responsible for translation repression in quiescent cells. In AR4-2J tumoral
      cells, we first demonstrated that gastrin increases ODC mRNA translation.
      Transient transfections with various CAT chimeric constructs suggested a direct
      involvement of the 5'UTR in this observation. Translation of this group of mRNAs
      is enhanced by the availability of the cap-binding protein (eIF4E) that is
      increased after phosphorylation of its specific binding protein eIF4E-BP1. We
      found that AR4-2J cells over-expressed eIF4E protein which was not modulated by
      gastrin treatment. Rapamycin which inhibits 4E-BP1 phosphorylation, completely
      prevents gastrin-mediated increase of ODC translation indicating that 4E-BP1
      could be involved in regulating ODC translation. Implication of 4E-BP1 in
      mediating gastrin effects is corroborated by the capacity of the ligand to affect
      4E-BP1 phosphorylation. These results indicate that gastrin enhances ornithine
      decarboxylase mRNA translation through a rapamycin sensitive pathway and provide
      the first evidence in the control of 4E-BP1 phosphorylation after occupancy of a
      G protein-coupled receptor.

PMID- 9619832
TI  - Regulation of BRCA1 and BRCA2 expression in human breast cancer cells by DNA
      damaging agents.
AB  - Germline mutations in the breast cancer susceptibility genes BRCA1 and BRCA2 have
      been linked to the development of breast cancer, ovarian cancer, and other
      malignancies. Recent studies suggest that the BRCA1 and BRCA2 gene products may
      function in the sensing and/or repair of DNA damage. To investigate this
      possibility, we determined the effects of various DNA-damaging agents and other
      cytotoxic agents on the mRNA levels of BRCA1 and BRCA2 in the MCF-7 and other
      human breast cancer cell lines. We found that several agents, including
      adriamycin (a DNA intercalator and inhibitor of topoisomerase II), camptothecin
      (a topoisomerase I inhibitor), and ultraviolet radiation induced significant
      decreases in BRCA1 and BRCA2 mRNA levels. Decreased levels of BRCA1 and BRCA2
      mRNAs were observed within 6-12 h after treatment with adriamycin and persisted
      for at least 72 h. Adriamycin also induced decreases in BRCA1 protein levels; but
      these decreases required several days. U.V. radiation induced dose-dependent down
      regulation of BRCA1 and BRCA2 mRNAs, with significant decreases in both mRNAs at
      doses as low as 2.5 J/m2, a dose that yielded very little cytotoxicity.
      Adriamycin-induced down-regulation of BRCA1 and BRCA2 mRNAs was first observed at
      doses that yielded relatively little cytotoxicity and little or no apoptotic DNA
      fragmentation. Adriamycin and U.V. radiation induced distinct dose- and time
      dependent alterations in the cell cycle distribution; but these alterations did
      not correlate well with corresponding changes in BRCA1 and BRCA2 mRNA levels.
      However, the adriamycin-induced reduction in BRCA1 and BRCA2 mRNA levels was
      correlated with p53 functional status. MCF-7 cells transfected with a dominant
      negative mutant p53 (143 val-->ala) required at least tenfold higher doses of
      adriamycin to down-regulate BRCA1 and BRCA2 mRNAs than did parental MCF-7 cells
      or control-transfected MCF-7 clones. These results suggest that BRCA1 and BRCA2
      may play roles in the cellular response to DNA-damaging agents and that there may
      be a p53-sensitive component to the regulation of BRCA1 and BRCA2 mRNA
      expression.

PMID- 9619833
TI  - Inhibition of telomerase increases the susceptibility of human malignant
      glioblastoma cells to cisplatin-induced apoptosis.
AB  - Malignant glioblastomas grow very rapidly and are generally resistant to either
      DNA-damaging drugs or gamma-irradiation. If tumor cells could be made more
      susceptible to cell death with treatments, this would clearly represent a
      significant improvement in the success of treatment. Recently, telomerase has
      become a focus of interest among oncologists as a target for treating cancer
      cells. Telomerase elongates telomeric DNA repeats (TTAGGG)n and is important in
      protecting and replicating DNA. The vast majority of tumor cells, indeed, express
      telomerase activity whereas normal somatic cells, except for a few cells, do not.
      Since telomerase is essential for protecting DNA, we may be able to make tumors
      more sensitive to treatments with DNA-damaging drugs by inhibiting telomerase
      activity. In this study, we used cis-diamminedichloroplatinum (cisplatin)
      sensitive U87-MG cells and cisplatin-resistant U251-MG of human malignant
      glioblastoma cell lines. U87-MG cells did not express telomerase activity,
      whereas telomerase was highly detected in U251-MG cells. Interestingly,
      inhibition of telomerase with an antisense telomerase expression vector not only
      decreased telomerase activity but also increased susceptibility to cisplatin
      induced apoptotic cell death in U251-MG cells. These findings suggest that
      treatment with antisense telomerase may represent a new chemosensitisation for
      tumors resistant to anticancer drugs.

PMID- 9619834
TI  - mdm2-P2 transcript levels predict the functional activity of the p53 tumor
      suppressor in primary leukemic cells.
AB  - The mdm2-P2 promoter is a transcriptional target of the p53 tumor suppressor. The
      aim of this study was to determine if there is an association between the level
      of these transcripts and the status of the p53 gene in human leukemic cells. A
      correlation between mdm2-P2 transcript levels and p53 gene status was observed in
      all cell lines examined. Primary malignant cells from 10 leukemic patients were
      also analysed for both mdm2-P2 levels and p53 gene status. All five patients with
      detectable mdm2-P2 transcripts possessed wild-type p53 alleles. However, only two
      of five patients with undetectable mdm2-P2 transcripts possessed mutant p53. mdm2
      P2 levels were also determined in primary leukemic cells from 14 additional cases
      both before and after in vitro exposure to cisplatin. The p53 gene was found to
      be wild-type in all cases where mdm2-P2 levels were induced by cisplatin. There
      were four cases where no, or only modest, increases in mdm2-P2 levels were
      detected after cisplatin exposure. Two of these patients were found to harbor
      mutant p53 while one other possessed leukemic cells with elevated levels of mdm2
      protein. These results show that induction of mdm2-P2 transcripts can be used to
      predict the presence of transcriptionally active p53 in primary leukemic cells.

PMID- 9619835
TI  - PTEN mutations in gliomas and glioneuronal tumors.
AB  - Cytogenetic and loss of heterozygosity studies have suggested the presence of at
      least one tumor suppressor gene on chromosome 10 involved in the formation of
      high grade gliomas. Recently, the PTEN gene, also termed MMAC1 or TEP1, on
      chromosomal band 10q23 has been identified. Initial studies revealed mutations of
      PTEN in limited series of glioma cell lines and glioblastomas. In order to
      systematically evaluate the involvement of PTEN in gliomas, we have analysed the
      entire PTEN coding sequence by SSCP and direct sequencing in a series of 331
      gliomas and glioneuronal tumors. PTEN mutations were detected in 20/142
      glioblastomas, 1/7 giant cell glioblastomas, 1/2 gliosarcomas, 1/30 pilocytic
      astrocytomas and 2/22 oligodendrogliomas. No PTEN mutations were detected in 52
      astrocytomas, 37 oligoastrocytomas, three subependymal giant cell astrocytomas,
      four pleomorphic xanthoastrocytomas, 15 ependymomas, 16 gangliogliomas and one
      dysembryoplastic neuroepithelial tumor. In addition, all tumors were examined for
      the presence of homozygous deletions of the PTEN gene; these were detected in 7
      glioblastomas that did not have PTEN mutations. Therefore, PTEN mutations occur
      in approximately 20% of glioblastomas but are rare in lower grade gliomas. These
      findings confirm that PTEN is one of the chromosome 10 tumor suppressor genes
      involved in the development of glioblastomas.

PMID- 9619836
TI  - Subcellular and submitochondrial mode of action of Bcl-2-like oncoproteins.
AB  - Bcl-2 is the prototype of a class of oncogenes which regulates apoptosis. Bcl-2
      related gene products with either death-promoting and death-inhibitory activity
      are critically involved in numerous disease states and thus constitute prime
      targets for therapeutic interventions. The relative amount of death agonists and
      antagonists from the Bcl-2 family constitutes a regulatory rheostat whose
      function is determined, at least in part, by selective protein-protein
      interactions. Bcl-2 and its homologs insert into intracellular membranes
      including mitochondria, the endoplasmatic reticulum and the nuclear envelope.
      Many of the molecular genetic, ultrastructural, crystallographic and functional
      studies suggest that Bcl-2-related molecules exert their apoptosis-regulatory
      effects via regulating mitochondrial alterations preceding the activation of
      apoptogenic proteases and nucleases. Via a direct effect on mitochondrial
      membranes, Bcl-2 prevents all hallmarks of the early stage of apoptosis including
      disruption of the inner mitochondrial transmembrane potential and the release of
      apoptogenic protease activators from mitochondria. The mitochondrial permeability
      transition (PT) pore, also called mitochondrial megachannel or multiple
      conductance channel, is a multiprotein complex formed at the contact site between
      the mitochondrial inner and outer membranes, exactly at the same localization at
      which Bax, Bcl-2, and Bcl-XL are particularly abundant. The PT pore participates
      in the regulation of matrix Ca2+, pH, deltapsim, and volume and functions as a
      Ca2+-, voltage-, pH-, and redox-gated channel with several levels of conductance
      and little if any ion selectivity. Experiments involving the purified PT pore
      complex indicate that Bax, Bcl-2, and Bcl-XL exert at least part of their
      apoptosis-regulatory function by facilitating (Bax) or inhibiting (Bcl-2, Bcl-XL)
      PT pore opening. These findings clarify the principal (but not exclusive)
      mechanism of Bcl-2-mediated cytoprotection.

PMID- 9619837
TI  - The BRCA2 is a histone acetyltransferase.
AB  - Patients carrying mutations in BRCA1 or BRCA2 tumor suppressor genes have shown
      to have high risk in developing breast and ovarian cancers. Two potential
      functions of BRCA2 were proposed which includes role in the regulation of
      transcription and also in DNA repair. Forty-five-amino acid region encoded by
      exon 3 of BRCA2 was shown to have transcriptional activation function. Recent
      studies of the several enzymes involved in acetylation and deacetylation of
      histone residues have revealed a possible relationship between gene
      transcriptional activation and histone acetylation. Since BRCA2 appear to
      function as a transcriptional factor, we have tested for Histone acetyl
      transferase (HAT) activity of BRCA2. Here, we present evidence that BRCA2 has
      intrinsic HAT activity, which maps to the amino-terminal region of BRCA2. Our
      results demonstrate that BRCA2 proteins acetylate primarily H3 and H4 of free
      histones. These observations suggest that HAT activity of BRCA2 may play an
      important role in the regulation of transcription and tumor suppressor function.

PMID- 9619838
TI  - Evi-1 ZF1 DNA binding activity and a second distinct transcriptional repressor
      region are both required for optimal transformation of Rat1 fibroblasts.
AB  - The Evi-1 gene encodes a zinc finger transcriptional repressor protein that
      normally plays a role in development and is frequently activated in myeloid
      leukaemias. Evi-1 has two distinct DNA binding domains, ZF1 and ZF2, and a
      defined repressor domain but the function of the remainder of the molecule is
      unknown. The ZF2 and repressor domains have been shown to be required for
      transformation and we show here that ZF1 is also required. An alternative splice
      variant of Evi-1, designated delta324, encodes a protein which lacks a portion of
      the ZF1 DNA binding domain and the intervening amino acids 239-514 (designated
      IR) located between ZF1 and the repressor domain. We show that delta324 can
      neither bind ZF1, repress transcription through this site nor transform Rat1
      fibroblasts. Reconstitution studies demonstrate that the defect in delta324 is
      partially complemented by recreating the ZF1 DNA binding activity. However, full
      function also requires the IR region which has transcriptional repressor
      activity. This study shows therefore, that ZF1, ZF2 and repressor domains and the
      IR region all contribute to the transformation efficiency of the Evi-1 protein.

PMID- 9619839
TI  - Uptake of 125I-PDGF-AB to the blood after extravascular administration in mice.
AB  - The kinetics of exogenously given 125I-platelet-derived growth factor-AB (PDGF
      AB) was studied in mice. 125I-PDGF-AB was injected either intraperitoneally,
      intramuscularly or subcutaneously and the resulting concentrations of 125I
      radioactivity monitored in the blood at different times. The serum levels of 125I
      radioactivity rose to a maximum 2-4 hours after injection, before decreasing.
      Precipitation of serum with trichloroacetic acid demonstrated that 50 per cent or
      more of the 125I remained in macromolecular form. Further, gel chromatography
      studies showed that the molecular size of the labelled material in serum, three
      hours after injection, was the same as that of the original 125I-PDGF-AB. In
      addition, a low-molecular weight fraction was observed, indicating the presence
      of degradation products. The largest proportion of degraded material was obtained
      after subcutaneous administration. The absence of partially degraded 125I
      labelled fragments, e.g. 125I oligopeptides, indicates complete rather than
      limited degradation and suggests that the 125I-PDGF-AB had been processed by
      cellular uptake. It is concluded that extra-vascularly given PDGF-AB in mice is
      taken up into the blood in intact macromolecular form. This finding suggests that
      it is possible to administer PDGF extravascularly to obtain a prolonged increase
      in the concentration of intact PDGF in the blood.

PMID- 9619840
TI  - Dopamine receptor mRNAs in the rat lymphocytes.
AB  - It has been suggested that dopamine might play a role in the regulation of the
      immune system. In this study, reverse transcriptase-polymerase chain reaction (RT
      PCR) was used to investigate the expression of mRNA for the different subtypes of
      dopamine receptors in the rat lymphocytes. D1, D3 and D5 receptor mRNAs were
      identified. These results provide further evidence for the interaction of
      dopamine systems and the immune system, and suggest to further investigate
      whether the immunosuppressive actions of dopamine and dopaminergic drugs might
      depend on a direct interaction with dopamine receptors on the lymphocyte
      membrane. Moreover, they suggest the suitability of this animal species to
      further investigate the correlation between changes in the expression of central
      and peripheral dopamine receptors produced by manipulations of the dopamine
      systems.

PMID- 9619841
TI  - Intrahippocampal injection of paraquat produces apoptotic cell death which is
      prevented by the lazaroid U74389G, in rats.
AB  - Injection of paraquat, a redox-cycling compound, into the rat hippocampus
      produces limbic seizures and hippocampal damage. Here we report that a proportion
      of the neuronal cell death caused by the herbicide occurs via an apoptotic
      mechanism which appears to be mediated by oxygen free radicals. Adult male Wistar
      rats (n=12) received a single dose of paraquat (25 nmol/0.5 microl; 0.5
      microl/min rate) and were sacrificed 24 h later. Paraquat caused DNA
      fragmentation, nuclear chromatin marginalization and compaction in all
      hippocampal subsectors, 24 h after its injection, as revealed by both the TUNEL
      procedure and hematoxylin eosin staining of coronal brain tissue sections. Pre
      treatment with the free radical scavenger lazaroid U74389G (30 mg/kg given i.p.
      30 min beforehand) significantly reduced paraquat-induced apoptosis, but did not
      protect against non apoptotic neuronal cell loss caused by the herbicide.

PMID- 9619842
TI  - PCA50941, a new 1,4-dihydropyridine, reverses endothelin-induced cardiogenic
      shock in the anesthetized goat.
AB  - This study was designed to test the hypothesis that the properties of novel 1,4
      dihydropyridine PCA50941 could favor the recovery of cardiogenic shock. Coronary
      blood flow (CBF), measured with an electromagnetic flow probe placed on the left
      circumflex coronary artery, systemic arterial pressure and heart rate were
      recorded in 24 anesthetized goats; left ventricular pressure and dP/dt were also
      recorded in 19 of these goats. Under control conditions, intracoronary injections
      in 5 goats of PCA50941 (10-120 microg) caused smaller reductions of CBF than
      those of Bay K 8644 (0.3-10 microg) (the reduction of CBF by 120 microg PCA50941
      was 25% and that by 10 microg Bay K 8644 was 43%), and i.v. infusions in 4 goats
      of PCA50941 (10-300 microg/min) did not modify CBF nor the other hemodynamic
      variables recorded, whereas i.v infusion of Bay K 8644 (10-30 microg/min) reduced
      CBF by 20% and increased arterial pressure, left ventricular pressure and dP/dt.
      During control conditions and endothelin-induced cardiogenic shock, respectively,
      the values for 15 goats were: for CBF, 33+/-4 vs. 16+/-4 ml/min; for mean
      arterial pressure, 88+/-4 vs. 60+/-5 mm Hg; for left ventricular systolic
      pressure, 102+/-5 vs. 75+/-4 mm Hg; for dP/dt, 1453+/-147 vs. 925+/-101 mm Hg/s
      (all P<0.05), and for heart rate, 77+/-6 vs. 81+/-6 beats/min (P>0.05).
      Intravenous infusion of PCA50941 (100 microg/min) reversed the hemodynamic
      variables from the shock state to control values within 20 min in 5 of 6 animals,
      whereas i.v. administration of Bay K 8644 (10-30 microg/min) was not effective in
      4 of 5 animals, and the vehicle (DMSO) was not effective in none of 4 animals in
      reversing the hemodynamic shock state. Therefore, it is suggested that PCA50941,
      a novel 1,4-dihydropyridine, has a cardiovascular profile that might be suitable
      for treating cardiogenic shock states.

PMID- 9619843
TI  - Effect of metyrapone administration in pregnant rats on monoamine concentration
      in fetal brain.
AB  - Studies performed in our laboratory indicate that the adrenal deprivation during
      gestation can greatly influence the fetal catecholamines development in several
      cerebral areas. The present study was undertaken to determine whether the
      administration of metyrapone to pregnant rats affects the content of monoamines
      in fetal brain at term. To test wether the content of monoamines in fetal brain
      is regulated, at least in part, by endogenous glucocorticoids, pregnant rats were
      injected for 5 days prior to delivery with metyrapone, an adrenal 11-beta-steroid
      hidroxylase inhibitor which crosses the placenta and blocks endogenous
      glucocorticoid synthesis, or saline. On day 21 of gestation, delivery of all
      animals was accomplished by cesarean section. The encephalons were extracted and
      immediately dissected in metencephalon, mesencephalon, diencephalon and
      telencephalon. Monoamine determination was carried out using HPLC-ED. The results
      obtained indicate that the metyrapone treatment increases both DA and 5-HT and
      their metabolites in the brain studied areas.

PMID- 9619844
TI  - Aromatase and testosterone receptor in the liver of the female green frog, Rana
      esculenta.
AB  - In the green frog, Rana esculenta, a peculiar feature of female reproductive
      endocrinology is an high level of circulating testosterone. Although several
      hypotheses have been set out to explain this phenomenon, the testosterone
      specific roles in female anuran have not been yet fully explored. This study
      results propose a testosterone implication in liver vitellogenin synthesis
      control, since in ovariectomized frogs the hormone induces an increase of
      circulating vitellogenin. The testosterone action could depend on its local
      conversion to 17beta-estradiol by aromatase which is present in frog liver
      tissue. Liver aromatase activity ranges from 7.5 to 26 fmoles E2 formed/mg
      protein/h and results higher as long as liver is engaged in vitellogenin
      synthesis. Aromatase activity seems depend on testosterone since it decreases
      after ovariectomy and is restored by testosterone injection in ovariectomized
      frogs. In green frog liver, testosterone binding molecules are present both in
      cytosol and nuclei. These molecule binding properties (Kd and Bmax in nM range; t
      1/2 = 85 min; specificity) are in line with those of testosterone receptor of
      other lower vertebrate target tissue. In liver nuclei, testosterone receptor
      level undergoes modification throughout the sexual cycle which almost coincides
      with that of plasma testosterone level and liver aromatase activity. This could
      indicate that the testosterone induction of liver aromatase in frogs is via the
      testosterone receptor, as reported for aromatase of mammalian brain tissues.

PMID- 9619845
TI  - Endothelin-1, acting via the A receptor subtype, stimulates thymocyte
      proliferation in the rat.
AB  - Endothelins (ETs) are a family of vasoactive peptides widely distributed in the
      body systems, where they carry out major autocrine/paracrine regulatory
      functions, acting through two main subtypes of receptors (ETA and ETB). Evidence
      suggests that ETs play a permissive role in the development of neural crest
      derived craniofacial structures, among which the thymus. Therefore, we have
      investigated whether ETs regulate thymocyte proliferation in the adult rat ET-1
      (which binds both ETA and ETB receptors) increased the mitotic index (% of
      metaphase-arrested cells) in the thymus cortex, while ET-3 (which preferentially
      binds ETB) and the selective ETB-receptor agonists BQ-3020 and IRL-1620 did not.
      The ETA-receptor antagonists BQ-123 and BQ-610, but not the ETB-receptor
      antagonist BQ-788, abolished the ET-1 effect. Moreover, BQ-123 and BQ-610, when
      administered alone, evoked a significant decrease in the mitotic index.
      Collectively, these findings clearly indicate that endogenous ETs, through the
      activation of ETA receptors, are involved in the maintenance and stimulation
      thymocyte proliferation in the adult rat, thereby playing a possible important
      role in the modulation of the immune-system functions.

PMID- 9619846
TI  - Transforming growth factor-beta receptor types I and II are expressed in renal
      tubules and are increased after chronic unilateral ureteral obstruction.
AB  - Transforming growth factor-beta (TGF-beta) is a profibrotic cytokine which has
      been implicated in the renal fibrosis which follows unilateral ureteral
      obstruction (UUO) in the rat. TGF-beta receptor type I (TGF-RI) and TGF-beta
      receptor type II (TGF-RII) are part of the complex which mediates the response to
      TGF-beta. We sought to determine if TGF-RI and TGF-RII are found in the kidney,
      and if their expression is changed as a result of UUO. Polymerase chain reaction
      (PCR) was used to determine expression of mRNA for TGF-RI and TGF-RII in the
      kidney. Immunoperoxidase was used to localize and quantify the expression of
      these receptors at 3, 7, 14, 21 and 28 days after UUO, and in sham-operated
      animals. Expression of mRNA for TGF-RI and TGF-RII was demonstrated in sham
      operated, obstructed and contralateral unobstructed kidneys using PCR. Using
      immunoperoxidase, a uniform distribution of TGF-RI and TGF-RII was found in
      cortical tubules of sham operated kidneys, whereas medullary tubules showed a
      patchy TGF-RI distribution and no TGF-RII staining. After UUO, an increased
      tubular expression of TGF-RI and TGF-RII was noted in both obstructed and
      contralateral kidneys compared to sham operated kidneys. No staining for either
      TGF-RI or TGF-RII was noted in glomeruli, vasculature or interstitial cells. TGF
      beta receptors I and II were found exclusively in renal tubules and were shown to
      increase in both the obstructed and contralateral kidneys relative to sham
      operated animals. Upregulation of TGF-beta receptors in both kidneys suggests
      that TGF-beta may contribute to the fibrotic response in the obstructed kidney
      and the hypertrophic response of the contralateral kidney.

PMID- 9619847
TI  - Quantitative analysis of alpha-fetoprotein mRNA in circulating peripheral blood
      of patients with hepatocellular and alpha-fetoprotein-producing gastric
      carcinomas.
AB  - In conjunction with strategies introduced in recent years to identify cancer
      micrometastasis through amplification of cancer-associated mRNA, we developed a
      highly sensitive system to detect alpha-fetoprotein mRNA in circulating
      peripheral blood of hepatocellular carcinoma patients. The aim of the present
      study was to make our original system quantitative. Peripheral venous blood from
      patients with hepatocellular carcinoma and alpha-fetoprotein-producing gastric
      carcinoma was subjected to reverse transcription followed by our original three
      step polymerase chain reaction co-amplifying both the original sequence and our
      synthetic competitor. We succeeded in modifying our system for quantitative
      analysis, and investigated the perioperative change, the postoperative change and
      the change after chemotherapy in order to illustrate the possible application of
      this method. The quantitative analysis of alpha-fetoprotein mRNA present in the
      peripheral blood represents a useful tool for analyzing the relationship of
      surgery to recurrence, the effect of chemotherapy, and to predict impending
      recurrence in patients with hepatocellular and alpha-fetoprotein-producing
      gastric carcinomas.

PMID- 9619848
TI  - Ginsenosides induce differential antinociception and inhibit substance P induced
      nociceptive response in mice.
AB  - Ginsenosides are main pharmacoactive molecules of ginseng. The antinociceptive
      activity of ginsenosides after intrathecal (i.t.) injection was examined in
      formalin test. We also investigated the effects of ginsenosides on substance P
      (SP) induced-pain behaviors by i.t. treatment using mice. Pretreatment of
      ginsenosides by i.t. induced the inhibition of biting and licking of hind paw
      injected with 1% formalin with dose-dependent manner. The ED50 was 23 (19-28, 95%
      C.I.) microg/mouse for acute phase and 15 (9-23, 95% C.I.) microg/mouse for tonic
      phase. Interestingly, cotreatment of ginsenosides with SP also inhibited SP
      induced pain behaviors (scratching, licking or biting of hind portion of body)
      with dose-dependent manner. The ED50 for the inhibition of SP-induced pain
      behavior by ginsenosides was 30 (11-85, 95% C.I.) microg/mouse. These results
      suggest that ginsenosides have antinociceptive activity in formalin test and this
      effect is due to blocking of SP-induced nociceptive information to postsynaptic
      site(s) at the spinal level.

PMID- 9619849
TI  - Cross tolerance to environmental stress and endotoxin.
AB  - Mild DIC-like phenomena develop in rodents exposed to environmental stress,
      induced by prolonged fluctuation in ambient temperature, known as SART (specific
      alternation of rhythm in temperature) stress, the symptoms being essentially
      similar to those produced by endotoxin. The aim of the present study was to
      investigate whether common mechanisms are involved in the stress-induced DIC-like
      phenomena and endotoxaemia. The mortality in mice after intraperitoneal injection
      with endotoxin at 8.3, 16.7 and 33.3 mg/kg increased in a dose-dependent manner.
      In the mice exposed to stress for 7 days, the death rate following endotoxin at
      8.3 mg/kg was markedly lower than that in unstressed mice, although no difference
      was detected between the two groups following endotoxin at 16.7 and 33.3 mg/kg.
      Conversely, repeated administration of endotoxin at a low dose, 0.5 mg/kg, during
      exposure to stress for 7 days inhibited the stress-induced thrombocytopenia and
      hypofibrinogenemia. These findings indicate the development of cross tolerance to
      prolonged environmental stress and endotoxin, implying involvement of a common
      mechanism.

PMID- 9619850
TI  - Inhibition of immune cell proliferation with haloperidol and relationship of
      tyrosine hydroxylase expression to immune cell growth.
AB  - Previous studies indicated that exogenous dopamine and its agonists directly
      regulated mitogen-induced immune cell proliferation. In this study, we further
      investigated role of endogenous dopamine in immune cell growth. Haloperidol, a
      general antagonist for dopamine receptors, could reduce the cell growth rate of T
      cell hybridoma (10I) and rat nervous pheochromocytoma cells (PC12). Tyrosine
      hydroxylase (TH) catalyzes the initial rate-limiting step of catecholamine
      biosynthesis in the nervous system. Flow cytometric analysis indicated the
      expression of TH in various immune cells. The presence of TH in PC12 cells was
      used as a control. Temporal studies indicated that the expression of TH increased
      during 10I cell growth. Both alpha-methyl-p-tyrosine and 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine reduced TH expression and cell growth in a dose
      dependent manner. These results suggest that immune T cells express TH which is
      correlated to cell growth, and that dopamine released from these cells may bind
      to the receptors to act in an autocrine or paracrine way.

PMID- 9619851
TI  - Induction of hepatic poly(ADP-ribose) polymerase by peroxisome proliferators, non
      genotoxic hepatocarcinogens.
AB  - Two peroxisome proliferators, [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]
      acetic acid (Wy-14,643) or di(2-ethylhexyl) phthalate (DEHP), were given orally
      to male F-344 rats for up to 78 or 97 weeks. At 1 week, the activity of poly(ADP
      ribose) polymerase (pADPRP) was increased 2- and 1.8-fold in the liver of rats
      treated with Wy-14,643 and DEHP, respectively. The induction of the activity was
      maintained at 2.5- or 2-fold for up to 52 weeks. The immunoblot and Northern blot
      analyses revealed that the induction of pADPRP activity would be responsible for
      the increase in the amount of mRNA. In addition, in the liver tumor induced by Wy
      14,643 and DEHP, the pADPRP mRNA level increased 3.6- or 3.7-fold. The magnitude
      of the increase in the mRNA level was higher than that in the non-tumor portion.
      These findings suggest that the induction of pADPRP may play an important role in
      the hepatocarcinogenesis induced by peroxisome proliferators.

PMID- 9619852
TI  - p16 gene overexpression in mouse bladder carcinomas.
AB  - Deletion of 9p21 has frequently been observed in human bladder carcinomas. A
      candidate target suppressor gene, p16, was recently identified within this
      deleted region. In this study, we therefore investigated the loss of
      heterozygosity (LOH) of the p16 gene which is located on mouse chromosome 4, as
      well as its expression in mouse bladder carcinomas. We also studied the effects
      of normal cell contamination on LOH analysis using xenografts in CD-1(ICR) nude
      mice from B6C3F1 bladder carcinomas. We could not detect any LOH at the p16 locus
      in the mouse primary bladder carcinomas and xenografts. Surprisingly,
      overexpression of p16 was found in all primary mouse bladder carcinomas. Using
      microsatellite polymorphisms, a distinction could be made between PCR products
      derived from B6C3F1 and CD-1(ICR) nude mice. It was thereby confirmed that
      effects of normal cell contamination on LOH analysis are negligible when only
      tumor tissue is carefully sampled. The results suggest that abnormalities of p16
      expression may be involved in mouse bladder carcinogenesis, but that gene
      deletion is not involved.

PMID- 9619853
TI  - Conjugated linoleic acid reduces arachidonic acid content and PGE2 synthesis in
      murine keratinocytes.
AB  - Dietary conjugated linoleic acid (CLA) is associated with decreased 12-O
      tetradecanoyl-phorbol-13-acetate (TPA)-induced tumor promotion in mouse skin. In
      addition, CLA decreases TPA-induced prostaglandin E synthesis and ornithine
      decarboxylase activity in cultured keratinocytes compared with linoleic acid (LA)
      and arachidonic acid (AA). When LA or CLA was added to keratinocyte cell
      cultures, the amounts of each of these cellular fatty acids increased
      significantly in a dose-dependent manner. Furthermore, LA treatment was
      associated with increased cellular AA while the AA content of keratinocytes was
      reduced when cultures were treated with CLA. Moreover, CLA (16 microg/ml) was
      more potent than LA at decreasing the level of 14C-AA incorporated into cellular
      phosphatidylcholine. In order to determine the effect of CLA on arachidonate
      derived PGE2, the release of 14C-AA and 14C-PGE2 synthesis was measured in
      cultures pre-treated with LA/14C-AA or CLA/14C-AA for 12 h. The amount of 14C-AA
      release induced by TPA in CLA/14C-AA pre-treated cultures was significantly lower
      than cultures pre-treated with LA/14C-AA. Furthermore, TPA-induced 14C-PGE2 was
      significantly lower in cultures pre-treated with CLA/14C-AA compared with
      cultures pre-treated with LA/14C-AA. The effects of LA and CLA on AA composition
      of phospholipids and subsequent arachidonate-derived PGE2 synthesis will provide
      insight into the anti-promoter mechanisms of CLA.

PMID- 9619854
TI  - Inhibition of fos-jun-DNA complex formation by dihydroguaiaretic acid and in
      vitro cytotoxic effects on cancer cells.
AB  - The effect of dihydroguaiaretic acid (DHGA), isolated from the aryls of Myristica
      fragrans, on the transcription factor (fos-jun dimer) action was investigated via
      in vitro assay. DHGA showed an inhibitory effect against the complex formation of
      the fos-jun dimer and the DNA consensus sequence with an IC50 value of 0.21
      micromol. Nordihydroguaiaretic acid (NDGA) and curcumin also inhibited fos-jun
      dimer action showing IC50 values of 7.9 and 6.9 nmol, respectively. DHGA and NDGA
      suppressed leukemia, lung cancer and colon cancer in an in vitro bioassay. The in
      vitro experiment suggested that inhibition of fos-jun-DNA complex formation could
      be due to the direct interference of fos-jun dimer binding onto the DNA consensus
      sequence by NDGA and curcumin.

PMID- 9619855
TI  - Production and regulation of interleukin-11 by breast cancer cells.
AB  - We have studied the production of interleukin-11 (Il-11) in 13 breast cancer cell
      (BCC) lines. Two of these cell lines (MDA-MB-231 and Hs578T) expressed the
      cytokine at both the protein and mRNA levels. Il-11 did not modulate the growth
      of five BCC lines examined, including the two cytokine-producing BCC lines. The
      production of Il-11 was increased by transforming growth factor-beta1 in a dose
      dependent manner with a rapid (2 h) and transient (24 h) mRNA induction, but not
      by epidermal growth factor, insulin-like growth factor-I and -II, basic
      fibroblast growth factor, platelet-derived growth factor or parathyroid hormone.
      The cyclic AMP inducer, forskolin, and the activator of protein kinase C, phorbol
      12-myristate 13-acetate, also stimulated the production of Il-11. Besides Il-11,
      MDA-MB-231 and Hs578T were the only BCC lines to produce interleukin-6 (Il-6)
      protein and mRNA. Since Il-11 and Il-6 are potent stimulators of osteoclast
      development and bone is a major source of TGF-beta1, our data suggest that Il-11,
      together with Il-6, contributes to the high bone destructive capacity of MDA-MB
      231 cells and could play a role in breast cancer-induced osteolysis.

PMID- 9619857
TI  - The effect of dietary vitamin D3 on the intracellular calcium gradient in
      mammalian colonic crypts.
AB  - A physiological gradient in intracellular calcium ([Ca2+]i) has been hypothesized
      to exist along the colonic crypt base-mouth axis, which may be involved in the
      regulation of colonocyte proliferation, differentiation and apoptosis. In
      addition [Ca2+]i may be modulated by dietary vitamin D3 which is thought to be
      protective against colorectal cancer. CF1 mice were maintained for 6 weeks on a
      defined diet containing either high or low vitamin D3. A colonic crypt base-mouth
      [Ca2+]i gradient of 201 +/- 79 nM (mean +/- SEM, P < 0.05) was observed in
      animals maintained on a high vitamin D3 diet and was abolished in mice maintained
      on a low vitamin D3 diet. The [Ca2+]i gradient was independent of extracellular
      calcium and elevated levels of [Ca2+]i observed in the basal regions of the crypt
      in animals maintained on low levels of vitamin D3 were also associated with an
      increase in intracellular calcium stores. Therefore, a [Ca2+]i gradient exists in
      colonic crypts and is dependent on dietary vitamin D3.

PMID- 9619856
TI  - Effects of doxycycline on human prostate cancer cells in vitro.
AB  - Prostate cancer is the most common form of cancer in older men and the major
      cause of death from prostate cancer is metastatic disease. The matrix
      metalloproteinases (MMPs) play a significant role in the growth, invasion and
      metastasis of many tumors, including those of the prostate. We previously
      demonstrated that doxycycline, a synthetic tetracycline, inhibits MMPs and cell
      proliferation and induces apoptosis in several cancer cell lines. We also
      demonstrated that in an in vivo model of metastatic breast cancer in athymic mice
      doxycycline inhibits tumor size and regrowth after resection. In the present
      study, gelatinolytic activity in the human prostate cancer cell line, LNCaP, was
      suppressed and significant inhibition of cell growth occurred after exposure to 5
      or 10 microg/ml of doxycycline, while cell growth was normal in untreated cells.
      Radioisotope incorporation into proteins was reduced by doxycycline. DNA
      fragmentation, consistent with apoptosis, was demonstrated in cells treated with
      doxycycline. These data suggest that doxycycline may have potential utility in
      the management of prostate cancer.

PMID- 9619858
TI  - High incidence of esophageal cancer in esophageal achalasia by the oral
      administration of N-amyl-N-methylnitrosamine and its prevention by nicardipine
      hydrochloride in mice.
AB  - Esophageal achalasia (EA) is a rare disease in man and animals and there are many
      discussions on its higher risk of esophageal cancer. N-Amyl-N-methylnitrosamine
      (AMN) which specifically induces esophageal tumors in mice and rats was given to
      three mutant mouse strains, i.e. 101/N, STX/Le and BXH-8, which develop a high
      incidence of EA. The incidence of EA in 101/N, STX/Le, BXH-8 and normal C57BL/6J
      mice was 38.5% (110/286), 30.1% (43/143), 91.8% (190/207) and 0% (0/167),
      respectively. The average numbers of AMN-induced esophageal tumors in EA(+) were
      significantly higher than those of EA(-) in all of the 101/N, STX/Le and BXH-8
      mice. Furthermore, significantly larger size tumors and invasive squamous cell
      carcinomas were found in EA(+) mice than in EA(-) mice. These results indicate
      the higher sensitivity of EA for both tumor induction and promotion, possibly due
      to the longer retention of AMN. In fact, relaxation of the lower esophagus by a
      smooth muscle relaxing calcium-channel blocker, nicardipine hydrochloride,
      significantly prevented the induction of esophageal tumors.

PMID- 9619859
TI  - Prolidase in human breast cancer MCF-7 cells.
AB  - Prolidase (EC 3.4.13.9) is an ubiquitously distributed imidodipeptidase that
      catalyzes the hydrolysis of dipeptides containing C-terminal proline or
      hydroxyproline. The enzyme plays an important role in the recycling of proline
      for collagen synthesis and cell growth. We have shown previously that prolidase
      activity in normal human skin fibroblasts is regulated by the interaction of type
      I collagen with beta1 integrin receptor. In the present study, we investigate
      prolidase activity in MCF-7 cells and find it is only one-third of that in normal
      human skin fibroblasts. The relative difference in prolidase activity is
      corroborated by enzyme protein with Western immunoblot analysis. We propose that
      the decrease in prolidase activity is due to derangement of regulation by the
      collagen-beta1 integrin receptor axis. Supporting evidence comes from the
      following observations: (1) relative collagen content elaborated by MCF-7 cells
      as compared to fibroblasts is lower by 30% in sparse cells and by 80% at
      confluence; (2) collagenase treatment of both cell types results in decreased
      enzyme activity; (3) in contrast to fibroblasts, prolidase activity in MCF-7
      cells is not stimulated by the addition of type I collagen or beta1 integrin
      antibodies (agonist for beta1 integrin receptor); and (4) in contrast to
      fibroblasts, MCF-7 cells express only trace amounts of beta1 integrin receptor as
      shown by Western immunoblot analysis. Thus, we conclude that depressed prolidase
      activity in MCF-7 cells may be a result of disturbances in signaling mediated by
      beta1 integrin-collagen interaction.

PMID- 9619860
TI  - Evaluation of the antineoplastic activity of guduchi (Tinospora cordifolia) in
      cultured HeLa cells.
AB  - Exposure of HeLa cells to 0, 5, 10, 25, 50 and 100 microg/ml of guduchi extracts
      (methanol, aqueous and methylene chloride) resulted in a dose-dependent but
      significant increase in cell killing, when compared to non-drug-treated controls.
      The effects of methanol and aqueous extracts were almost identical. However,
      methylene chloride extract enhanced the cell killing effect by 2.8- and 6.8-fold
      when compared either to methanol or aqueous extract at 50 and 100 microg/ml,
      respectively. Conversely, the frequency of micronuclei increased in a
      concentration-dependent manner in guduchi-treated groups and this increase in the
      frequency of micronuclei was significantly higher than the non-drug-treated
      control cultures and also with respect to 5 microg/ml guduchi extract-treated
      cultures, at the rest of the concentrations evaluated. Furthermore, the
      micronuclei formation was higher in the methylene chloride extract-treated group
      than in the other two groups. The dose response relationship for all three
      extracts evaluated was linear quadratic. The effect of guduchi extracts was
      comparable or better than doxorubicin treatment. The micronuclei induction was
      correlated with the surviving fraction of cells and the correlation between cell
      survival and micronuclei induction was found to be linear quadratic. Our results
      demonstrate that guduchi killed the cells very effectively in vitro and deserves
      attention as an antineoplastic agent.

PMID- 9619861
TI  - Protective effects of cruciferous seed meals and hulls against colon cancer in
      mice.
AB  - Protective effects of diets containing cruciferous seed meals or hulls against
      chemically-induced colon tumors were examined in male CF1 mice. When commercial
      crambe meal, autolyzed crambe meal, crambe hulls, high glucosinolate rapeseed
      meal, or canola meal were fed as 12% of the diets of mice injected with 1,2
      dimethylhydrazine, 25-80% of the animals developed colon tumors. Animals fed a
      soybean meal control diet had a 100% tumor rate. Data suggest that cruciferous
      seed meals may contain a number of compounds that can exert protective effects
      against tumor formation and growth.

PMID- 9619862
TI  - Immunohistochemical analysis of steroid hormone receptors in nasopharyngeal
      angiofibromas.
AB  - Juvenile nasopharyngeal angiofibroma arises almost exclusively in pubertal and
      adolescent men and has potentially aggressive behavior with a spread into
      adjoining sinuses and bone destruction. It is classically being regarded as an
      androgen hormone-dependent tumor, but no in situ evaluation of androgen receptors
      has been done. The author has examined eight nasopharyngeal angiofibromas (six
      primary and two recurrent tumors) for the expression of androgen receptor (AR),
      estrogen receptor (ER) and progesterone receptor (PR) using immunohistochemical
      methods and compared those results with a sex- and age-matched control group
      consisting of eight samples of nasal turbinates. No ER or PR were found in any of
      the tumor components, nor have they been detected in control nasal turbinates.
      Angiofibromas were characterized by variable weak (+) nuclear androgen receptor
      immunoreactivity found in a minority of endothelial and stromal cells, similar to
      the normal turbinates. These results argue against the significant role of
      androgen receptor in the growth of nasal angiofibromas and corroborate previous
      observations of an unpredictable response of these neoplasms to antiandrogen
      therapy.

PMID- 9619863
TI  - Influence of tobacco smoke on DNA unwinding and uterotrophic effect of estrogens
      in rats.
AB  - Experiments with a duration of either 3 weeks or 3 months were conducted on
      female rats with initial body weights of 140-170 g. All animals were divided into
      four groups, i.e. control, tobacco smoke (TS, a whole-body exposure to the
      mainstream cigarette smoke), estrogen (EG, diethylstilbestrol) and TS + EG.
      Injection of EG started on the day of bilateral ovariectomy which was performed
      in all animals 11 days before the end of the experiment. In short 3-week
      experiments TS weakly stimulated uterine wet weight and in combination with EG
      significantly increased the percentage of intact non-unwound DNA in uterine
      tissue (stimulation stage). In the longer 3-month experiments TS decreased a
      specific hormonal effect of EG, i.e. the ability to induce progesterone receptors
      in uterine tissue, and did not interfere with the DNA-damaging effect of
      diethylstilbestrol. The conclusion was made that different phases exist in
      hormonal and genotoxic responses to the combined effect of tobacco smoke and
      estrogens, which may be related to the mechanisms and types of hormonal
      carcinogenesis.

PMID- 9619864
TI  - Effect of liposomalization on the antitumor activity, side-effects and tissue
      distribution of CPT-11.
AB  - We have examined the efficacy of liposomalization and polyethyleneglycol (PEG)
      modification of liposomes on the antitumor activity, side-effects and tissue
      distribution of irinotecan hydrochloride (CPT-11). PEG-liposome was confirmed to
      elevate the plasma circulation of CPT-11 and SN-38 (active metabolite)
      concentrations. The tumor accumulation of CPT-11 and SN-38 was increased by the
      PEG-modified liposomes. The antitumor activity of CPT-11 increased due to the
      elevated tumor distribution of CPT-11 and SN-38 levels by the PEG-modified
      liposomes. In the tumor, CPT-11 was converted to SN-38. Thus, it is considered
      that passive targeting to the tumor by liposomalization elevated the SN-38 level
      in the tumor especially and increased the antitumor activity of CPT-11.
      Furthermore, intestinal disorder, a side toxicity of CPT-11, decreased dependent
      on the CPT-11 and SN-38 concentrations in the bile by liposomalization. Although
      the liposomes induce improved tissue distribution of the prodrug, the tissue
      distribution of active metabolites does not always improve. However, CPT-11
      entrapped liposome was useful, as CPT-11 is converted to SN-38 in the tumor.
      These results suggested that the usefulness of CPT-11 could be extended.

PMID- 9619865
TI  - Alpha-tocopherol antagonizes the multidrug-resistance-reversal activity of
      cyclosporin A, verapamil, GF120918, clofazimine and B669.
AB  - The effects of the membrane-stabilizing agent, alpha-tocopherol (25 microg/ml),
      on the chemosensitizing interactions of cyclosporin A (5 microg/ml), verapamil (2
      microg/ml), clofazimine (1 microg/ml), B669 (0.5 microg/ml) and GF120918 (0.015
      microg/ml) with a P-glycoprotein-expressing human lung cancer cell line (H69/LX4)
      have been investigated in vitro. In an assay of cell proliferation, all the
      chemosensitizing agents restored the sensitivity of H69/LX4 cells to doxorubicin
      and vinblastine. The inclusion of alpha-tocopherol (25 microg/ml) antagonized the
      multidrug-resistance (MDR)-modifying activity of all five chemosensitizing
      agents, effectively preventing restoration of sensitivity to both doxorubicin and
      vinblastine in H69/LX4 cells.

PMID- 9619866
TI  - Intracellular calcium distribution in apoptosis of HL-60 cells induced by
      harringtonine: intranuclear accumulation and regionalization.
AB  - Harringtonine (HT), an anticancer drug with high chemotherapeutic efficiency to
      human chronic granulocytic/myelomonocytic leukemia, has been reported to rapidly
      induce apoptosis in HL-60 cells in a wide scope/range of dosage by investigators
      from our lab and others. In the present studies, by using video enhancement
      contrast (VEC) microscopy, we dynamically analyzed changes in intracellular
      calcium distribution in a single HL-60 cell over the period from the initiation
      of apoptosis to the obvious appearance of chromatin condensation. The results
      from this paper demonstrated the striking distinction of intracellular calcium
      distribution at different time points after treatment with HT. Before treatment
      in normal HL-60 cells the highest [Ca2+]i accumulation was observed in the peri
      nuclear area and the lowest was observed in the nucleus; after treatment with 1
      microg/ml HT for 30 min intracellular calcium diffused all over the cell
      compartments, while intranuclear calcium increased comparatively and
      significantly. The phenomenon of intranuclear calcium accumulation was further
      confirmed by using laser scanning confocal microscopy (LSCM). In addition, co
      localization of the highest calcium region with condensed chromatin in apoptotic
      HL-60 cells was also observed by LSCM. Our results suggest that two sequential
      alterations of intracellular calcium distribution occurred in apoptotic HL-60
      cells induced by HT, i.e. (a) accumulation of calcium in the nucleus and (b)
      regionalization in a specific nuclear region.

PMID- 9619867
TI  - Glycogen content in the gastric mucosa of partially resected stomach; a possible
      relationship with the development of cancer.
AB  - Since gastric carcinoma, unlike uninvaded mucosa, has a relatively high glycogen
      content and the risk of gastric carcinoma is especially high in patients with a
      partially resected stomach, the aim of this study was to follow glycogen storage
      in both uninvaded gastric stump mucosa and carcinoma developing in the stump
      postsurgery performed for benign and malignant conditions. One hundred patients
      were recruited, including controls with non-operated stomachs (duodenal ulcer or
      gastric cancer patients). In endoscopically taken biopsies glycogen was
      determined by the anthrone method. It was found that the glycogen content in the
      gastric remnants was higher than in non-operated stomachs and increased with the
      time after surgery. It is possible that the risk of gastric cancer, which
      increases with the time from surgery, may be related to glycogen storage.

PMID- 9619868
TI  - Activated lymphocytes from breast cancer patients express the characteristics of
      type 2 helper cells--a possible role for breast cancer-associated p43.
AB  - P43, a breast cancer-associated antigen, has been repeatedly described as an
      immunosuppressive factor. The objective of the present study was to investigate
      whether immune dysregulation induced by p43 affects the profile of cytokines
      secreted by mitogen-stimulated lymphocytes in breast cancer patients as compared
      with stimulated lymphocytes in women with benign tumors. The study consisted of
      32 women undergoing surgical excision for a suspicious lesion in their breast.
      Histology revealed malignant breast disease in 20 patients and benign lesions in
      10 patients. Lymphocytes isolated from peripheral blood were activated by
      Conconavalin A (Con A) with and without the addition of p43 and the
      concentrations of cytokines (IL-2, TNF-alpha, IFN-gamma, IL-4, IL-10 and IL-6)
      secreted into the culture medium were determined. Lymphocytes of patients with
      malignant breast disease stimulated with Con A secreted a significantly higher
      concentration of IL-10 compared with lymphocytes of patients with benign tumors.
      No significant differences were found between the two groups regarding the levels
      of IL-2, TNF-alpha, IFN-gamma and IL-4. Cytokine concentrations were analyzed
      according to the type 1/type 2 cytokine profile (IL-2, TNF and IFN-gamma and IL
      4, IL-6 and IL-10, respectively). This analysis revealed no significant
      differences in IL-2, TNF or IFN-gamma between benign and malignant tumors.
      However, in the type 2 cytokines, lymphocytes from cancer patients secreted
      significantly higher levels of IL-4 (27.3 +/- 7.2 U/ml) and IL-10 (44.1 +/- 22.3
      U/ml) than did the lymphocytes from patients with benign disease (21.4 +/- 7.3
      and 1.8 +/- 0.3 U/ml, respectively). The addition of p43 to the culture medium
      significantly enhanced the levels of IL-4 secreted by lymphocytes in both groups
      of patients (malignant disease, from 27.3 +/- 9.2 to 40.7 +/- 6.3 U/ml; benign
      disease, from 21.4 +/- 7.3 to 28.4 +/- 2.1 U/ml). P43 antigen significantly
      enhanced the low levels of IL-10 in the benign lymphocytes (from 1.8 +/- 0.4 to
      8.4 +/- 1.5 U/ml) while the high levels of IL-10 secreted by the PBL in patients
      with malignant tumors were not significantly increased (44.1 +/- 22.3 versus 50.1
      +/- 12.6 U/ml). The study showed a difference in the immune response of
      lymphocytes between malignant and benign tumors. When the current results were
      analyzed according to the type of response, i.e. in terms of whether at least two
      cytokines of either type 1 or type 2 were elevated, a significant type 2 response
      was observed in the PBL of patients with malignant breast cancer (IL-10 and IL
      4). These results may explain why antitumor response is impaired in patients with
      breast cancer.

PMID- 9619869
TI  - Toxicological evaluation of sobatum.
AB  - Sobatum, the partially purified component of the plant Solanum trilobatum was
      obtained from the petroleum ether/ethyl acetate (75:25) extractable portion. It
      was identified as beta-sitosterol by comparison with an authentic sample and
      proved to be an anticancer agent by in vitro and in vivo experiments. The aim of
      the present study is to evaluate the acute/subacute toxicity of sobatum and its
      effect on antioxidant enzymes. In the acute toxicity test, there was a single
      exposure of sobatum in mice in order to evaluate toxicity symptoms. In the
      subacute toxicity study, the exposure was usually daily so as to evaluate the
      target organs affected by the compound and the major toxic effects and enzymatic
      and histopathological changes. The results of the study suggested that sobatum
      did not induce any toxic symptoms or death immediately after injection or at the
      end of the experimental period. It was also shown that there was no change in
      blood parameters or antioxidant enzymes in sobatum-treated animals. Regarding
      histopathological evaluation, there was no development of gross abnormalities or
      pathological lesions observed in any of the tissues in sobatum-treated and
      control groups. Hence, the present study concluded that the anticancer agent,
      sobatum, did not produce any acute/subacute toxicities or anomalies in the
      synthesis of antioxidant enzymes.

PMID- 9619870
TI  - The substrate specificity of the rat hepatic cytosolic arylamine oxidase
      catalyzing the bioactivation of aromatic amines.
AB  - The ability of the cytosolic arylamine oxidase to convert structurally diverse
      aromatic and heterocyclic amines to mutagens in the Ames test was investigated
      using hepatic cytosol from Aroclor 1254-treated rats as the activation system.
      Using this system, only amino compounds containing at least three fused aromatic
      rings elicited a strong mutagenic effect; heterocyclic amines failed to exhibit
      mutagenicity. In contrast, when Aroclor 1254-induced rat hepatic microsomal
      preparations served as the activation system, monocyclic, bicyclic as well as
      larger amino compounds induced a clear mutagenic response; moreover, heterocyclic
      amines were potent mutagens. Nitrosamines displayed mutagenicity in the presence
      of only the microsomal activation system. In the presence of the cytosol, the
      mutagenic response of aromatic amines was much lower in the bacterial strain TA98
      1,8-DNP6, which is deficient in O-acetyltransferase activity, compared to the
      normal TA98 strain. This finding implies that the cytosolic activation of
      aromatic amines involves N-hydroxylation.

PMID- 9619871
TI  - 4-Piperidinopiperidine-resistant lymphoma cells were resistant to dexamethasone-
      and A23187-induced apoptosis.
AB  - 4-Piperidinopiperidine is a side residue of CPT-11, a derivative of camptothecin.
      We have previously established a 4-piperidinopiperidine-resistant lymphoma cell
      line, 4-pp-R, which was co-resistant to CPT-11. We report here that this cell
      line is cross-resistant to dexamethasone and A23187 which induce apoptosis in
      parent RVC cells. Examination of apoptosis-related gene expression by RT-PCR
      showed that bcl-2 expression was greater in 4-pp-R than in RVC. p53, bax and bcl
      xL were expressed at the same level in 4-pp-R and RVC cells. These results
      suggest that upregulation of bcl-2 in 4-pp-R cells is related to the resistance
      to CPT-11 as well as to A23187 or dexamethasone.

PMID- 9619872
TI  - A novel method of assessing carcinoma cell proliferation by biophoton emission.
AB  - Changes in the emission intensities of ultraweak biophoton emission during the
      cell proliferation of human carcinoma cell culture (TE9 cell line) were detected
      using a highly sensitive and low noise measurement apparatus coupled with a flow
      culture system. In the sampling period of 93 h, the biophoton emission intensity
      from the culture followed a similar course as that of the growth curve. Spectral
      analysis of the biophoton emission from the cell culture demonstrated a
      significant peak at around 530 nm. Our results suggest that the emission
      intensity mainly depends on the cell population and that this noninvasive
      technique has a potential role in cancer diagnosis.

PMID- 9619873
TI  - Expression of connexin32 and connexin43 gap junction proteins and E-cadherin in
      human lung cancer.
AB  - We used immunohistochemical staining to examine the expression of the gap
      junction proteins connexin32 and connexin43 and of the intercellular adhesion
      molecule, E-cadherin, that is thought to be a prerequisite for gap junctional
      intercellular communication (GJIC), in 24 specimens of human lung cancer.
      Connexin32 was not found in cancer tissue and there were significantly fewer
      spots of connexin43 in the poorly differentiated versus the well differentiated
      (P = 0.0005) and moderately differentiated (P = 0.0002) adenocarcinomas and in
      the poorly differentiated versus the well differentiated (P = 0.0182) and
      moderately differentiated (P = 0.004) squamous cell carcinomas of the lung. E
      Cadherin was expressed in all but three cases of poorly differentiated non-small
      cell lung cancer that showed a heterogeneously decreased expression of E
      cadherin. These findings suggest that GJIC is decreased in poorly differentiated
      non-small cell lung cancer.

PMID- 9619874
TI  - Internalization with high targeting potential of mouse monoclonal antibody ONS
      M21 recognizing human malignant glioma antigen.
AB  - In order to evaluate the targeting potential of mouse monoclonal antibody ONS-M21
      recognizing a human astrocytoma- and medulloblastoma-associated antigen, the
      internalization ability of this antibody and the selective cytotoxicity in the
      toxin-conjugated form were examined. Internalization assay with 125I-labeled ONS
      M21 showed that about 20% of the total radioactivities was detected in the
      cellular fraction of human medulloblastoma cell line ONS-76 cells and that the
      reaction reached a plateau level in 30 min. To examine the selective delivery
      capacity of a high molecular substance in place of 125I, an immunotoxin was
      prepared with ricin A chain and ONS-M21 via disulfide bonds. A cytotoxic effect
      against ONS-76 cells was found with [3H]thymidine incorporation assay using the
      immunotoxin, but not against antigen-negative HuH-7 and SW480 cells. These
      results suggest that ONS-M21 could effectively deliver toxins, chemotherapeutic
      agents or radionuclei to malignant glioma specifically.

PMID- 9619875
TI  - Inhibitory effects of plumbagin and juglone on azoxymethane-induced intestinal
      carcinogenesis in rats.
AB  - The effects of two naphthoquinones, juglone and plumbagin, and an isocoumarin,
      hydrangenol, on intestinal carcinogenesis in rats were examined by dietary
      exposure during the initiation phase. Starting at 5 weeks of age, male F344 rats
      were fed the diets containing either of the test chemicals at a concentration of
      200 ppm or the control diet without the compounds. At 6 weeks of age, all animals
      were treated with s.c. injections of azoxymethane (AOM) (15 mg/kg body weight,
      once weekly for 3 weeks) or saline alone. Animals fed experimental diets were
      changed to the control diet 1 week after the last carcinogen treatment. Animals
      given plumbagin together with the carcinogen had a lower incidence (41%) and
      smaller multiplicity (0.48 +/- 0.62) of tumors in the entire intestine compared
      with those exposed to carcinogen alone (68% and 1.04 +/- 0.62) (P < 0.05 and <
      0.01, respectively). The incidence and multiplicity of tumors in the small
      intestine (7% and 0.07 +/- 0.25) and the multiplicity of tumors in the entire
      intestine (0.60 +/- 0.76) of animals treated with juglone and the carcinogen were
      significantly less than those of animals treated with carcinogen alone (P < 0.05
      in each). Hydrangenol tended to decrease the incidence and the multiplicity of
      tumors in the entire intestine induced by AOM, but the effect was not
      statistically significant. The present data suggest that the naphthoquinones,
      juglone and plumbagin, could be promising chemopreventive agents for human
      intestinal neoplasia.

PMID- 9619876
TI  - Similarities between the sensitivity to 2-chlorodeoxyadenosine of lymphocytes
      from CLL patients and bryostatin 1-treated WSU-CLL cells: an infrared
      spectroscopic study.
AB  - Infrared (IR) spectroscopy was used to compare the drug resistance mechanism of
      cells from chronic lymphocytic leukemia (CLL) patients with that of WSU-CLL
      cells. Bryostatin 1 (Bryo 1), a macrocyclic lactone and protein kinase C
      activator, was used to render WSU-CLL cells more susceptible to 2
      chlorodeoxyadenosine (2-CdA). The IR spectroscopic analysis revealed some changes
      in protein and DNA content in Bryo 1-treated WSU-CLL cells, however, the most
      significant alterations were observed in the membrane lipids, which resemble
      those found between 2-CdA-sensitive and 2-CdA-resistant cells from CLL patients.
      In addition, Bryo 1 treatment induced WSU-CLL cells to become CD11c, CD25 and
      tartrate-resistant acid phosphatase-positive, specific markers for hairy cell
      leukemia, a disease exquisitely sensitive to 2-CdA. Our results suggest that 2
      CdA-sensitive CLL cells have cellular characteristics resembling the hairy cell
      stage. The similarity between the membrane lipids in 2-CdA-sensitive CLL cells
      and the Bryo 1-treated WSU-CLL cell line supports the suggestion that membrane
      lipid alteration might be an important step in the drug resistance mechanism of
      CLL cells.

PMID- 9619877
TI  - A subcloned human esophageal squamous cell carcinoma cell line with low
      thrombomodulin expression showed increased invasiveness compared with a high
      thrombomodulin-expressing clone--thrombomodulin as a possible candidate for an
      adhesion molecule of squamous cell carcinoma.
AB  - Thrombomodulin (TM) is an endothelial cell surface glycoprotein which converts
      thrombin from a procoagulant protease to an anticoagulant. We have previously
      reported that TM is a useful marker for immunohistochemical diagnosis of
      angiogenic tumors and also have reported that TM is expressed on squamous cell
      carcinoma (SCC) of the human esophagus. In addition, the expression of TM is
      significantly decreased in metastatic foci in lymph nodes compared with that in
      primary lesions. In order to reveal the biological significance of TM in SCC, we
      subcloned and established two different cell lines, i.e. TM-high-expressing
      (TE3HTM) cells and TM-low-expressing (TE3LTM) cells, from a human SCC cell line,
      TE3, using fluorescence-activated cell sorter (FACS) and examined the biological
      characteristics of these variant cell lines. These tumor cells revealed very
      similar morphological figures in ordinary cultured conditions and showed almost
      equal growth rates under various cultured conditions. By the invasion assay of
      these tumor cells using matrigel, we found that TE3LTM cells showed significantly
      increased invasive ability compared with that of TE3HTM cells. Characteristic
      intercellular localization of TM and a different manner of invasiveness between
      TE3LTM cells and TE3HTM cells suggest that TM may act as a cell-to-cell
      interaction molecule.

PMID- 9619878
TI  - Orthotopic growth and metastasis of human non-small cell lung carcinoma cell
      injected into the pleural cavity of nude mice.
AB  - We have constructed a metastatic model of human non-small cell lung cancer
      (NSCLC) by injection of NSCLC cell lines directly into the left pleural cavity of
      BALB/c nude mice. All of seven NSCLC cell lines, which are tumorigenic after
      subcutaneous injection, were successfully transplanted in the pleural cavity,
      while only three of the seven cell lines produced lung metastatic colonies after
      intravenous injection. Tumors grew extensively in the pleural cavity and
      infiltrated into the lung parenchyma directly. Furthermore, tumors metastasized
      to the mediastinum and contralateral pleural cavity through lymphatic routes.
      Since this model is easy to perform and the result is reproducible, it would be
      useful for studies on the biological behavior and treatment of human NSCLC in
      vivo.

PMID- 9619879
TI  - Myc activation reduces fibroblast clonogenicity via an apoptotic mechanism that
      can be suppressed by a soluble paracrine factor.
AB  - The c-Myc transcription factor is involved in the regulation of cellular
      proliferation and differentiation and is one of the most frequently deregulated
      genes in human cancers. While c-Myc is known to enhance the proliferative
      potential of cells, its activation in immortalized fibroblasts has been found to
      result in apoptosis following gamma-irradiation or under adverse growth
      conditions, including serum deprivation and hypoxia. When plating Rat-1
      fibroblasts at low cell densities (100 cells/100 mm plate), we observed a
      substantial reduction in the clonogenicity of cells with deregulated c-Myc
      activity compared to cells with normal c-Myc activity. This difference in
      clonogenicity was apparent despite the fact that cells were plated in media
      containing sufficient serum and oxygen concentrations known to suppress apoptosis
      of exponentially growing Rat-1 fibroblasts with activated c-Myc. Therefore, we
      hypothesized that the observed reduction in plating efficiency in cells with
      activated c-Myc occurred via an apoptotic mechanism and that a fibroblast-derived
      factor was required for suppression of apoptosis. Overexpression of the anti
      apoptotic oncogene, Bcl-2, in cells with activated c-Myc restored the plating
      efficiency to normal levels in cells plated at low cell densities. This strongly
      suggested that the decreased clonogenicity of fibroblasts with altered c-Myc
      activity resulted from enhanced apoptosis of the cells under these conditions.
      Furthermore, plating cells on a feeder layer of lethally-irradiated fibroblasts
      or in Rat-1 conditioned media increased the plating efficiencies of sparsely
      plated cells in a dose-dependent fashion. These results suggest that in addition
      to previously reported requirements for serum-derived growth factors and normal
      oxygen conditions, a paracrine factor liberated by Rat-1 fibroblasts is required
      to suppress c-Myc-induced apoptosis in these cells.

PMID- 9619880
TI  - Heterogeneous pattern of gene expression in cloned cell lines established from a
      rat transplantable osteosarcoma lung metastatic nodule.
AB  - We have established three cloned cell lines (COS1NR, COS2NR and COS4NR) from the
      lung metastatic nodule of a highly metastatic variant of rat transplantable
      osteosarcoma, C-SLM. All three clones shared the same morphological
      characteristics and tumorigenicity, but their growth rates in vitro and
      metastatic ability in vivo differed from each other. Single-strand conformation
      polymorphism (SSCP) analysis revealed all three clones to have the same p53 gene
      mutation and parent C-SLM tumor. On the other hand, Northern blot analysis showed
      a different pattern of expression for the genes, c-fos, c-jun, c-Ha-ras, transin
      (rat stromelysin), bone Gla protein (osteocalsin) and nm23/NDP kinase. These
      results indicate the presence of a heterogeneous cell population in terms of the
      different pattern of gene expression in a lung metastatic nodule of rat
      osteosarcoma and the present newly established cell lines will be useful for
      further investigation of the biological behavior of osteosarcomas.

PMID- 9619881
TI  - Prevention of cartilage breakdown by matrix metalloproteinase inhibition--a
      realistic therapeutic target?

PMID- 9619882
TI  - Anti-Jo-1 antibodies in polymyositis or dermatomyositis: evaluation by ELISA
      using recombinant fusion protein Jo-1 as antigen.
AB  - We evaluated an enzyme-linked immunosorbent assay (ELISA) for detecting anti-Jo-1
      antibodies in patients with polymyositis (PM) or dermatomyositis (DM) by use of
      the recombinant fusion protein Jo-1. Sera from 64 patients with PM or DM, from 80
      patients with other connective tissue diseases, and from 64 healthy subjects
      matched for age, sex and race, were studied by the ELISA and by the double
      immunodiffusion (DID) method. Eight patients with myositis (six PM, one DM and
      one DM with malignancy) with positive anti-Jo-1 by DID also showed positive
      results by the ELISA method, whereas five patients with positive anti-Jo-1 by
      this ELISA showed negative results on DID. One of the five had non-specific
      results. The incidence of positive results for anti-Jo-1 with the ELISA (18.8%)
      was greater than that for DID (12.5%), but the difference was not statistically
      significant. All patients with positive results for anti-Jo-1 by DID were also
      positive by the ELISA. The ELISA system with the recombinant Jo-1 antigen was
      useful in the detection of anti-Jo-1 antibodies in patients with PM/DM.

PMID- 9619883
TI  - Assessing patients' priorities and perceptions of the quality of health care: the
      development of the QUOTE-Rheumatic-Patients instrument.
AB  - Patient views on the quality of care have always been assessed by means of
      patient satisfaction questionnaires. The objectives of this study were to develop
      an instrument that would: (1) produce more specific data on health care services;
      (2) produce data that are related to the needs and expectations of individual
      clients; (3) contain items that had been formulated in collaboration with
      patients; (4) measure quality of health care services from the perspective of
      customers; (5) produce data on generic items and on disease-specific items of
      health care services. The instrument, developed for measuring the quality of care
      from the perspective of non-institutionalized rheumatic patients (QUOTE-Rheumatic
      Patients), was evaluated in 425 non-institutionalized patients suffering from
      rheumatic diseases. The internal consistency of the subscales, the presumed
      factor structure and the feasibility of the instrument were evaluated. The
      development of this instrument resulted in a self-administered questionnaire on
      the quality of health care from the perspective of non-institutionalized
      rheumatic patients, which contains proper scientific characteristics and provides
      specific information for practical quality assurance policies.

PMID- 9619884
TI  - Cogan's syndrome with Takayasu's arteritis.
AB  - Cogan's syndrome may be associated with large-vessel arteritis. We describe a
      patient with ocular inflammation, sensorineural hearing loss and arm claudication
      in whom a diagnosis of 'atypical' Cogan's syndrome and Takayasu's arteritis was
      made. All symptoms resolved with treatment.

PMID- 9619885
TI  - Knowledge in patients with rheumatoid arthritis: a longer term follow-up of a
      randomized controlled study of patient education leaflets.
AB  - Despite the wide availability of disease-related leaflets, their impact on
      patients' knowledge and well-being has rarely been evaluated. A randomized
      controlled study of a 'Rheumatoid Arthritis' leaflet revealed increased knowledge
      among the intervention group after 3 weeks. In addition, the leaflet was viewed
      as a source of reassurance. The purpose of the follow-up study was to determine
      whether the increase in knowledge was maintained in the longer term and to
      examine psychological well-being. Eighty-four patients (42 intervention and 42
      control) completed the 6 month follow-up. There were no significant changes (P >
      0.01) in mean outcome measures over the period 3 weeks-6 months for either the
      intervention or control groups. Patients in the intervention group retained the
      increase in knowledge observed at 3 weeks. Moreover, there was no evidence of
      adverse reactions to the leaflet in terms of psychological distress. Leaflets can
      be effective in promoting longer term increases in knowledge.

PMID- 9619886
TI  - Neck mobility assessment in ankylosing spondylitis: a clinical study of nine
      measurements including new tape methods for cervical rotation and lateral
      flexion.
AB  - The objective was to carry out a clinical assessment of different cervical
      mobility measurements in ankylosing spondylitis (AS), including two new tape
      methods for measuring cervical rotation and lateral bending. A range of cervical
      movements was measured in 52 consecutive male AS patients and the results
      correlated with detailed radiological changes in the whole spine and sacroiliac
      joints. Occiput- and tragus-to-wall distance (OWD/TWD), cervical rotation (CR)
      and lateral flexion (CLF) using a Myrin inclinometer (My) and a tape method (t),
      cervical flexion-extension (CFl-CExt/My) motion and chin chest distance (CCD)
      measurements were taken and repeated (test-retest). The results showed a highly
      significant correlation of all measurements with cervical radiological changes,
      except for CCD, and also those of OWD/TWD with lumbar changes. CLF and CExt also
      correlated significantly with lumbar changes, other measurements did not, and
      only TWD and CExt correlated with thoracic changes. All measurements showed good
      reliability, intra-class correlation coefficients (ICC) ranging from 0.89 to
      0.98. Occiput- or tragus-to-wall distance, cervical extension and lateral flexion
      proved to be valid and reliable measurements in AS, but cervical rotation also
      appeared to be a clinically relevant method. Cervical lateral flexion is a
      recommendable measurement for clinical trials in AS. The two new tape methods for
      measuring cervical rotation and lateral bending were as valid and reliable as the
      inclinometer method (Myrin), but also quick and easy. Chin-to-chest distance was
      not among the most valid tests in AS.

PMID- 9619887
TI  - The association of soft-tissue rheumatism and hypermobility.
AB  - Soft-tissue rheumatism (STR--tendinitis, bursitis, fasciitis and fibromyalgia)
      accounts for up to 25% of referrals to rheumatologists. The estimated prevalence
      of generalized hypermobility in the adult population is 5-15%. There have
      previously been suggestions that hypermobile individuals may be predisposed to
      soft-tissue trauma and subsequent musculoskeletal pain. This study was designed
      to examine the mobility status and physical activity level in consecutive
      rheumatology clinic attendees with a primary diagnosis of STR. Of 82 patients up
      to age 70 yr with STR, 29 (35%) met criteria for generalized hypermobility.
      Hypermobile compared to non-hypermobile individuals reported significantly more
      previous episodes of STR (90% vs 51%, P < 0.01), and more recurrent episodes of
      STR at a single site (69% vs 38%, P < 0.001). Although we were unable to show any
      difference in the time spent carrying out physical activity between the two
      groups, the hypermobile patients were performing significantly more repetitive
      activities. When specific anatomical sites of STR were analysed, small joints
      (elbows, hands and feet) currently affected with STR were more likely to show
      localized hypermobility than if those joints were asymptomatic. These findings
      suggest that hypermobility may be a factor in the development of STR. Repetitive
      activity may be a contributing factor towards STR in some hypermobile
      individuals.

PMID- 9619888
TI  - Severe intestinal involvement in Wegener's granulomatosis: report of two cases
      and review of the literature.
AB  - The clinical and pathological manifestations of severe intestinal involvement in
      Wegener's granulomatosis were studied by a review of the literature and reports
      of two patients. Altogether, six cases, two females and four males, were studied.
      One patient developed two episodes of bowel manifestations necessitating
      immediate surgical interventions. The average age at onset of intestinal symptoms
      was 43.3 yr (26-55 yr) and, in all cases, the first signs of such manifestations
      developed within the first 2 yr of disease. Prior to the onset of intestinal
      symptoms, immunosuppressive therapy was administered in six of seven instances.
      Acute abdominal pain with signs of peritonitis or distention only constituted the
      main clinical picture in six of the seven events. The last episode was manifested
      clinically with profuse diarrhoea with blood and mucus. Of the seven instances of
      severe intestinal manifestations, the small bowel was involved in two, the large
      bowel in three, and both the small and large bowel were affected in two episodes.
      Histological evidence of vasculitis in the bowel was demonstrated in three of the
      seven biopsy specimens, while in four, ischaemia, inflammation and ulceration
      were the pathological findings. Intestinal perforation was seen four times and
      surgery was performed in six of seven episodes. Severe intestinal involvement is
      rare in Wegener's granulomatosis. The initial bowel manifestations occur within
      the first 2 yr of disease, and affect both the large and small bowel.
      Histologically, vasculitis, ischaemia, inflammation and ulceration are the
      prevailing findings. Death due to intestinal catastrophy occurred in one of the
      six patients reported. Most likely, the manifestations are associated with the
      disease process rather than related to the use of immunosuppressive agents.

PMID- 9619889
TI  - Depression and depressive symptoms in rheumatoid arthritis patients: an analysis
      of their occurrence and determinants.
AB  - The objectives were to determine the differences in depressive symptoms and
      depression between rheumatoid arthritis (RA) and osteoarthritis (OA) patients,
      and to analyse the contribution of sociodemographic and clinical variables to
      depression in RA patients. The responses of 60 Egyptian RA patients and 40
      patients with OA of the knees to the Symptom Checklist-90-R Depression subscale
      were compared. The proportions of patients from both groups confirmed by a
      psychiatric interview to be clinically depressed according to the DSM-III-R
      criteria were also compared. The contributions of sociodemographic and disease
      variables to depressive symptoms and clinical depression in RA patients were
      explored by multiple linear and logistic regression, respectively. RA patients
      showed significantly higher depression scores than OA patients (P = 0.001). The
      difference was unaffected by controlling for the effects of age, sex, disease
      duration and the sociodemographic covariates. A depressive disorder was
      clinically confirmed in 23% of RA patients and 10% of OA patients. The
      erythrocyte sedimentation rate (ESR), being unmarried and an urban residence were
      significant predictors of depressive symptoms (P < 0.05), while being unmarried
      (P < 0.05, OR = 2.1) and HAQ disability (P < 0.01, OR = 3.8) were significant
      predictors of clinical depression in RA patients. RA patients have significantly
      more depressive symptoms and tend to be more clinically depressed than OA
      patients. The contribution of some sociodemographic and clinical variables to
      depression in RA patients was modest, albeit significant.

PMID- 9619890
TI  - Comparison of IgA-alpha1-antitrypsin levels in rheumatoid arthritis and
      seronegative oligoarthritis: complex formation is not associated with
      inflammation per se.
AB  - Serum complexes between IgA and alpha1-antitrypsin (IgA alpha1AT) have been found
      at raised levels in early rheumatoid arthritis (RA), where they appear to be
      associated with more erosive disease. We have now measured the levels of these
      complexes in the sera and synovial fluid of patients with RA and seronegative
      oligoarthritis to determine whether there is a relationship between complex
      levels and joint inflammation, and if bacterial stimulation of the mucosa is
      associated with complex formation in seronegative oligoarthritis. IgA-alpha1AT
      complexes were measured in patients with RA (n = 75) and seronegative
      oligoarthritis, with or without definite reactive arthritis (n = 28), using a
      newly developed sandwich ELISA. The results were compared with serum levels from
      healthy volunteers (n = 30). IgA and alpha1AT were also measured using ELISA and
      radial immunodiffusion (RID) techniques, respectively. IgA-alpha1AT complex
      levels in the sera of RA patients [mean = 25.6 arbitrary units (au)] were
      significantly higher (P = 0.0034) than those in patients with seronegative
      oligoarthritis (mean = 12.36 au) and healthy controls (mean = 8.08 au). There was
      no evidence for the inflamed joint being the source of IgA-alpha1AT complexes
      since synovial fluid levels were lower than corresponding serum levels, although
      higher amounts were found in RA than seronegative oligoarthritis (12.84 au vs
      4.11 au, P = 0.01). Serum levels of IgA and alpha1AT were similar in RA and
      seronegative oligoarthritis patients, and were higher than in normals. There was
      a significant correlation between complex and serum IgA levels in RA (r = 0.49, P
      < 0.001) and seronegative oligoarthritis (r = 0.53, P < 0.001) patients, although
      no relationship was found with alpha1AT levels. There was no correlation with
      other markers of the acute-phase response (C-reactive protein, erythrocyte
      sedimentation rate), nor with any clinical markers. In RA patients, serum complex
      levels were significantly higher in seropositive than seronegative patients
      (30.75 vs 16.48 au, P = 0.03), and we have demonstrated that a small amount of
      alpha1AT may be complexed with IgA rheumatoid factor. Our data suggest that the
      formation of IgA-alpha1AT complexes is not associated with inflammation per se,
      and does not appear to be related to bacterial stimulation of the mucosal immune
      system in patients with seronegative oligoarthritis.

PMID- 9619891
TI  - Loss of bone mineral density in Chinese pre-menopausal women with systemic lupus
      erythematosus treated with corticosteroids.
AB  - The adverse effect of disease and chronic corticosteroid therapy on bone mineral
      density (BMD) in patients with systemic lupus erythematosus (SLE) has been
      reported in several studies of Caucasian populations. As the factors controlling
      bone homeostasis may be different in Asian populations, we measured BMD in 52 pre
      menopausal Chinese women (mean age 34.1 +/- 8.0 yr) with SLE (mean disease
      duration 6.4 +/- 4.5 yr) treated with prednisone (mean daily dose 11.4 +/- 10.8
      mg/day). Lumbar spine, hip (total and subregions) and total body BMDs were
      measured in the SLE patients using dual-energy X-ray absorptiometry (DEXA), and
      compared with those from healthy controls matched for age, sex and body mass
      index. Compared to controls, SLE patients were found to have lower BMD (g/cm2) at
      several sites: the lumbar spine (0.98 vs 0.90, P = 0.001), Ward's triangle (0.72
      vs 0.67, P = 0.03), total body (1.04 vs 1.01, P = 0.04) and total hip (0.87 vs
      0.82, P = 0.05). There was no correlation between BMD at any region and duration
      of disease, activity of disease or prednisone therapy (mean daily dose,
      cumulative dose or treatment duration). When BMDs were compared between controls
      and SLE patients, subgrouped according to those not on calcium and those
      arbitrarily receiving calcium supplements (1 g/day), significantly lower BMDs
      were found in those not on calcium compared to both controls and SLE patients on
      calcium. BMDs in SLE patients on calcium were not different from those in
      controls. The low prevalence of osteoporosis in our SLE patients (4-6%) suggests
      significant loss of BMD in Chinese SLE patients on corticosteroid therapy is less
      than that reported in Caucasians (12-18%).

PMID- 9619892
TI  - Association of HLA-DR with susceptibility to and clinical expression of
      rheumatoid arthritis: re-evaluation by means of genomic tissue typing.
AB  - The clinical expression of rheumatoid arthritis (RA) varies considerably among
      individual patients. Genetic variations in human leucocyte antigen (HLA) may
      influence clinical expression. We re-examined the association of HLA-DR with
      susceptibility to and clinical expression of RA using genomic tissue typing,
      since most studies were based on (less reliable) serological techniques. Seventy
      eight patients with recent-onset RA, all participating in a clinical trial on
      therapeutic strategies, were HLA-DR typed by means of low-resolution genomic
      typing. Cumulative disease activity within the first 3 yr of disease was
      measured. Of the RA patients, 54% expressed DR4 (DR4+) vs 26% of healthy
      controls. Rheumatoid factor (RF)-positive patients had a higher cumulative
      disease activity than RF-negative patients. Patients who were either DR1+ or DR4+
      had a higher cumulative disease activity than those who expressed neither DR1 nor
      DR4. This association was less obvious after correction for RF status. The
      association of DR52+ (DR3, 5, 6) and a lower cumulative disease activity could
      also not be demonstrated after correction for RF status. Among RF-negative
      patients, DR51+ (or DR2+) was associated with a higher cumulative disease
      activity. Other HLA-DR types (including DR1 and DR4 separately) were not
      associated with the severity of RA. DR4 was associated with susceptibility to RA
      in our patients; HLA-DR low-resolution genomic tissue typing did not yield
      additional information to RF status for the clinical identification of individual
      patients with a poor prognosis.

PMID- 9619893
TI  - Active conservative treatment of atlantoaxial subluxation in rheumatoid
      arthritis.
AB  - Twenty patients with rheumatoid atlantoaxial subluxation (AAS) underwent an
      active conservative treatment programme, aiming at relieving the symptoms and
      influencing the natural course of AAS. The treatment consisted of intensive
      multiprofessional intervention in the hospital for a fortnight, and control and
      motivational visits 6 and 12 months later. The patients self-evaluated the
      symptoms several times, and the cervical spine radiographs were taken at the
      first and last visit. Seventeen of the 20 patients adopted the instructions well
      and undertook the exercise programme at least weekly, even after a 12 month
      follow-up. Cervical pain was significantly reduced (P < 0.001) during the first
      intervention, and the favourable effect continued at least 12 months. Promising
      changes were also seen in some cervical radiographs. It is possible to educate
      and motivate AAS patients to take active care of their neck, and to relieve their
      chronic neck pain significantly. Atlantoaxial instability may also be reduced
      during active conservative treatment.

PMID- 9619894
TI  - Erosive arthritis in systemic lupus erythematosus: analysis of a distinct
      clinical and serological subset.
AB  - Erosive arthritis (EA) in systemic lupus erythematosus (SLE) can be debilitating
      and deforming with uncertain factors for risk, although antibodies to the A2
      hnRNP core protein, known as anti-RA33, have been associated with EA. Two hundred
      patients under long-term follow-up for SLE were evaluated for EA and associated
      clinical and serological abnormalities. In addition, sera were tested in a masked
      fashion for anti-RA33 antibodies in a total of 60 patients: 10 with EA and 50 age
      , sex- and ethnically matched controls. Ten of 200 (5%) patients with SLE, mainly
      non-white women, had EA. There were trends for increased renal involvement (P =
      0.06), Sjogren's syndrome (P = 0.07) and Raynaud's phenomenon (P = 0.03) in
      patients with EA compared to those without EA. Rheumatoid factor (RF) was
      increased in patients with EA (P < 0.02), as were antibodies to double-stranded
      DNA (P < 0.05), Sm (P < 0.01) and La/SS-B (P < 0.001). Anti-RA33 antibodies were
      present in 70% with EA compared to 28% without EA (P < 0.05). RF correlated with
      anti-RA33 antibodies in patients with EA, but not with the presence of anti-RA33
      alone. Thus, anti-RA33 antibodies may identify those patients with SLE who are at
      risk for EA, and an association with RF suggests a common immune response or
      pathological mechanism in autoimmune erosive joint disease.

PMID- 9619895
TI  - Measuring health status in British patients with rheumatoid arthritis:
      reliability, validity and responsiveness of the short form 36-item health survey
      (SF-36).
AB  - The objective was to assess the performance of the SF-36 health survey (SF-36) in
      a sample of patients with rheumatoid arthritis (RA) stratified by functional
      class. The eight SF-36 subscales and the two summary scales (the physical and
      mental component scales) were assessed for test retest reliability, construct
      validity and responsiveness to self-reported change in health. In 233 patients
      with RA, the SF-36 scales were: reliable (intra-class correlation coefficients
      0.76-0.93); correlated with American College of Rheumatology (ACR) core disease
      activity measures [Spearman r = -0.12 (erythrocyte sedimentation rate) to -0.89
      (Modified Health Assessment Questionnaire)]; and responsive to improvements in
      health (standardized response means 0.27-0.9). The distribution of scores on four
      of the eight subscales (physical function, role limitations physical, role
      limitations emotional and social function) was clearly non-Gaussian. Very marked
      floor effects were noted with the physical function scale, and both ceiling and
      floor effects with the other three subscales. The two SF-36 physical and mental
      component summary scales are reliable, valid and responsive measures of health
      status in patients with RA. Six of the eight subscales meet standards required
      for comparing groups of patients, and the physical function and general health
      scales may be suitable for monitoring individuals. The two scales measuring role
      limitations have poor measurement characteristics. The SF-36 pain and physical
      function scales may be suitable for use as patient self-assessed measures of pain
      and physical function within the ACR core disease activity set.

PMID- 9619896
TI  - The assessment of knowledge in ankylosing spondylitis patients by a self
      administered questionnaire.
AB  - The aim of the present study was to assess ankylosing spondylitis (AS) patients'
      level of knowledge, using a self-administered multiple-choice questionnaire. The
      questionnaire, based on the Arthritis and Rheumatism Council (ARC) leaflet on AS,
      examined four areas: (A) general knowledge; (B) immunogenetic tests and
      inheritance; (C) general management; (D) joint protection, pacing and priorities.
      Statistical analysis was used to validate the questionnaire and to examine
      correlations with gender, age, disease duration and level of general education.
      The questionnaire was consistent, reliable and easy to read. The results showed
      AS patients to have a high level of knowledge (mean = 19.4, maximum possible =
      25), although some wrong beliefs about the role of blood tests, the HLA-B27
      antigen and inheritance were discovered. No statistical correlation was found
      between gender, age, duration of the disease, level of general education and the
      level of knowledge. These data suggest that this questionnaire is a simple way to
      detect the level of knowledge of patients with AS. The average score achieved by
      AS patients was outstanding, possibly reflecting the good quality of previous
      educational programmes. Patients' confusion regarding blood tests, genetics and
      inheritance was highlighted and should be addressed.

PMID- 9619897
TI  - Foot pain: specific indications for scintigraphy.
AB  - Bone scintigraphy is requested as part of the investigation of foot pain, but its
      contribution to clinical management has not been comprehensively documented.
      Previously published data are limited; the most comprehensive series identified
      scintigraphic abnormalities in patients with primarily orthopaedic problems and a
      control group was not included (Maurice HD et al. J Bone Joint Surg 1987;69B:448
      52). The aim of this study was to evaluate whether bone scintigraphy may be
      useful in different clinical circumstances indicated by referral request details.
      Regions of scintigraphic abnormality were scored and compared with clinical
      details drawn from case notes of 60 patients with foot pain. The commonest
      clinical indications for scans were: confirmation of the clinical suspicion of
      plantar fasciitis, documentation of the extent of inflammatory arthritis and
      location of focal pathology. A group of 30 asymptomatic, age- and sex-matched
      controls were also studied. In 14 out of 19 symptomatic feet in the plantar
      fasciitis group, focal uptake at the medial calcaneal tubercle was present,
      confirming the diagnosis. In patients with non-specific, diffuse foot pain, the
      bone scan identified focal abnormalities in 11 out of 14 cases, thus directing
      the clinician to the site of pathology. Scintigraphy also proved useful in
      mapping local inflammatory disease. Technetium-99m methylene diphosphonate image
      abnormalities occurred in the control group most commonly in the midfoot (16
      regions in 13 subjects) and first metatarsophalangeal joint (19 regions in 14
      subjects).

PMID- 9619898
TI  - Magnetic resonance imaging-detected avascular osteonecrosis in systemic lupus
      erythematosus: lack of correlation with antiphospholipid antibodies.
AB  - We determined prospectively the prevalence of avascular osteonecrosis (AON) by
      magnetic resonance imaging (MRI) of both lower limbs in a group of 40 systemic
      lupus erythematosus (SLE) patients, and correlated the results with their serum
      antiphospholipid antibody (APL Ab) status and their glucocorticoid (GC) intake.
      APL Ab were detected by anticardiolipin ELISA and by lupus anticoagulant assays.
      Cumulated prednisolone doses were computed by chart review. The prevalence of AON
      was 37.5%, with most patients being asymptomatic despite involvement of multiple
      sites. The number of epiphyseal, metaphyseal and diaphyseal AON sites per patient
      did not differ between APL Ab-positive and APL Ab-negative patients nor between
      patients with high and low APL Ab titres. By contrast, a striking correlation was
      found between the prevalence and severity of AON and GC therapy. In conclusion,
      this prospective MRI study indicates that the prevalence of AON in SLE patients
      correlates strongly with GC therapy, but not with APL Ab status.

PMID- 9619900
TI  - The risk of treatment. A study of rheumatoid arthritis patients' attitudes.
AB  - Despite its importance, there is no well-validated method of measuring patients'
      concept of 'acceptable' risk of medical treatment. Numerical methods give widely
      varying results depending on the methodology. We have attempted to assess
      'acceptable' risk using relative comparisons. We administered a questionnaire to
      67 patients with rheumatoid arthritis (RA). In general, patients' estimate of
      acceptable risk was less than the actual risk of treatment. Some illogical
      choices were made, showing poor understanding by patients of the concepts of risk
      and risk:benefit ratio. Patients appeared willing to accept higher levels of risk
      from procedures than from drug treatment. Willingness to accept risk in exchange
      for successful treatment of their RA did not correlate with disease severity,
      age, willingness to take non-medical risks or family responsibilities.

PMID- 9619899
TI  - The role of germline polymorphisms in the T-cell receptor in susceptibility to
      ankylosing spondylitis.
AB  - The role of germline polymorphisms of the T-cell receptor A/D and B loci in
      susceptibility to ankylosing spondylitis was investigated by linkage studies
      using microsatellite markers in 215 affected sibling pairs. The presence of a
      significant susceptibility gene (lambda > or = 1.6) at the TCRA/D locus was
      excluded (LOD score < -2.0). At the TCRB locus, there was weak evidence of the
      presence of a susceptibility gene (P = 0.01, LOD score 1.1). Further family
      studies will be required to determine whether this is a true or false-positive
      finding. It is unlikely that either the TCRA/D or TCRB loci contain genes
      responsible for more than a moderate proportion of the non-MHC genetic
      susceptibility to ankylosing spondylitis.

PMID- 9619901
TI  - Sporotrichial bursitis.

PMID- 9619902
TI  - Non-Hodgkin's lymphoma of the femur presenting as a pathological fracture in a
      patient with lupus/Sjogren's syndrome overlap.

PMID- 9619903
TI  - Management of dermato-rheumatic syndromes.

PMID- 9619904
TI  - No additive effect of cyclosporin A compared with glucocorticoid treatment alone
      in giant cell arteritis: results of an open, controlled, randomized study.

PMID- 9619905
TI  - Mannose-binding protein gene polymorphism in South African systemic lupus
      erythematosus.

PMID- 9619906
TI  - Diffuse proliferative glomerulonephritis in Behcet's syndrome.

PMID- 9619907
TI  - Cervical spine fracture in ankylosing spondylitis: a case of 'auto-fracture'.

PMID- 9619908
TI  - Ultrastructural demonstration of intracellular localization of Borrelia
      burgdorferi in Lyme arthritis.

PMID- 9619909
TI  - Androgenizing effects of low-dose cyclosporin in male patients with early RA.

PMID- 9619910
TI  - Thymoma associated with rheumatoid arthritis after D-penicillamine treatment.

PMID- 9619911
TI  - Epidemiology of myelodysplastic syndromes in a French general hospital of the
      Basque country.
AB  - Epidemiologic studies concerning myelodysplastic syndromes (MDS) are rare. The
      estimated incidence varies between 1 and 12.6/100,000/year. The aim of this work
      was to compare our own experience with these data. Our general hospital
      represents a structure with 1197 beds which serves a population of 290,000
      individuals (French Basques). Most of the inhabitants live in a rural
      environnement. Twenty percent of the population are aged over 65. During a 4-year
      period (1993-1996), 90 new cases of MDS were diagnosed on bone marrow studies in
      our laboratory. Among FAB subtypes refractory anemia (RA) represented 27 cases
      (31%), RA with ring sideroblasts (RARS): 21 (23%), RA with excess of blasts
      (RAEB) and in transformation (RAEB-t): 22 (24%), chronic myelomonocytic leukemia
      (CMML): 10 (11%). Ten cases were unclassifiable (11%). Therapy-related MDS were
      seen in 8 patients. The sex ratio was 1 and the mean age of the patients was 74.3
      (range: 23-96), 37% of them being 80 years or older. The calculated incidence was
      7.7/100,000/year for the entire cohort and 31.4/100,000/year for people over 65.

PMID- 9619912
TI  - Engraftment following mitoxantrone (Mito) based conditioning for allogeneic bone
      marrow transplantation (allo-BMT).
AB  - Mitoxantrone (Mito) is presently used in an increasing number of malignancies
      including leukemias, breast carcinomas and solid tumors. With it has come
      increased incidence of post remission cytopenias and delayed engraftment
      following autologous bone marrow transplantation (ABMT). We evaluated engraftment
      in 18 patients who underwent allogeneic BMT (allo-BMT) following a preparative
      regimen that included high dose Mito (60 mg m2). Sixteen patients with malignant
      disease (AML 10, ALL 3, CML 2, MDS 1) and two with non-malignant disease (SCID 1,
      osteopetrosis 1) underwent non-T cell depleted allo-BMT. Fourteen patients with
      malignancies were transplanted at an advanced stage of disease while only two
      patients were standard risk patients. Of the 18 patients, 12 were females and six
      males, with a median age of 30.5 (0.3-48) years. Nine patients, (breast cancer 3,
      malignant lymphoma 4 and AML 2), who underwent ABMT following preparative
      regimens with comparable doses of Mito, served as controls. Engraftment following
      allo-BMT was normal and not statistically different from engraftment following
      ABMT. Five patients, who underwent allo-BMT, developed >grade II acute graft
      versus host disease (GVHD) and two developed chronic GVHD. After a median follow
      up of 28 (6-42) months, five patients are alive (one with disease). In summary,
      engraftment following high dose Mito and allo-BMT is not statistically different
      from engraftment following ABMT. Controlled studies with a larger group of
      standard risk patients are needed to elucidate the role of Mito in conditioning
      regimens pre-BMT.

PMID- 9619913
TI  - Hematologic engraftment and reconstitution of immune function post unrelated
      placental cord blood transplant in an adult with acute lymphocytic leukemia.

PMID- 9619914
TI  - Cell cycle perturbations in acute myeloid leukemia samples following in vitro
      exposures to therapeutic agents.
AB  - Cell cycle checkpoints establish the timing and strength of arrest, repair and
      apoptosis responses to damaging treatments. We designed flow cytometric assays to
      measure cell cycle arrest and apoptosis in acute myeloid leukemia (AML) samples
      treated in vitro with relevant therapeutic agents so as to functionally
      characterize checkpoints in these samples and to ask if checkpoint abnormalities
      are common in AML and contribute to therapeutic failures. We show here that cell
      cycle responses to daunomycin (DNR), cytosine arabinoside (ARA-C) and gamma
      irradiation (RAD) were reproducibly treatment agent- and dose-dependent and
      distinct in different myeloid cell lines. DNR treatments differentially induced
      cell accumulations in the gap 2 and mitosis (G2/M) phases of the cell cycle
      and/or in the gap 1 (G1) phase, as did RAD, while ARA-C induced accumulations in
      the DNA synthesis (S) phase or in the G1 phase. Flow cytometric gates were
      devised to exclude lymphocytes and mature neutrophils in analyses of primary
      myeloid cell samples. Cell subsets in bone marrow samples from normal donors were
      thus enriched for myeloid constituents and used as normal myeloid cell controls.
      Proliferating cell nuclear antigen (PCNA) immunostaining was used to further
      identify actively dividing cell subpopulations in primary cell samples. AML
      samples were similarly analyzed and the majority showed lower DNA synthesis cell
      cycle phase (S) fractions and lower PCNA-positive fractions than normal myeloid
      cells, suggesting that AMLs are generally less proliferative in these culture
      conditions. Exceptional AML samples with high S phase fractions had cytogenetic
      abnormalities associated with poor prognosis. Most AML samples mounted weak cell
      cycle responses relative to normal myeloid cells, while a minority showed robust,
      agent-specific cell cycle arrests. This non-responsiveness was not simply
      associated with lower cycling indices-neither the response patterns nor the
      degrees of response were correlated with untreated S phase fractions or with PCNA
      positive fractions. Cell cycle responses were also not associated with clinical
      parameters including patient age, FAB class, or white blood cell count, nor with
      immunophenotypic features including CD34 status, nor with specific cytogenetic
      markers. This suggests that functional cell cycle response assays could provide
      unique diagnostic information in AML. These assays might also have prognostic
      value as ARA-C induced G1 arrests and DNR-specific G2/M arrests tended to be
      associated with failure to achieve clinical remission. In addition, G1 arrests
      after ARA-C and G2/M accumulations after DNR treatments tended to be more robust
      in samples that had previously been shown to be more highly immunopositive for
      bcl-2 expression. This data suggests that the association of bcl-2 expression
      with particular cell cycle responses to therapeutic agents may contribute to the
      association of bcl-2 with poor clinical responses in AML. These data provide the
      basis for further laboratory studies aimed at examining specific cell cycle
      arrests as mechanisms of therapeutic resistance and prospective studies aimed at
      rigorously assessing the prognostic utility of in vitro assays of checkpoint
      function.

PMID- 9619915
TI  - GCSF augments post-progenitor proliferation in serum-free cultures of
      myelodysplastic marrow while ATRA enhances maturation.
AB  - All-trans retinoic acid (ATRA) and granulocyte colony stimulating factor (GCSF)
      are potential inducers of myeloid progenitor cell growth and neutrophil
      differentiation in myelodysplasia (MDS). We have compared the effects of ATRA and
      GCSF on the colony growth of 10 MDS marrows, in semi-solid and liquid serum-free
      mononuclear cell (MNC) cultures, supplemented with a mixture of stem cell factor
      (SCF), interleukin 3 (IL-3) and granulocyte-monocyte colony stimulating factor
      (GmCSF) (SIGm mix), which is fully-supportive for myeloid and erythroid (with
      erythropoietin (EPO)) colony formation in normal marrow. Only 1/10 MDS patients
      produced normal granulocyte-macrophage colony-forming cell (GmCFC) numbers, under
      SIGm conditions and erythroid colonies (ECFC) were subnormal in all patients.
      ATRA (10(-7) M) increased GmCFC numbers (P=0.05) in semi-solid cultures of
      normal, but not MDS marrow MNC and decreased erythroid colonies in cultures of
      marrow from either source (P=0.008 and P=0.0001 for normal and MDS,
      respectively). ATRA enhanced neutrophilic maturation in liquid cultures of both
      normal and myelodysplastic CD34 + ve cells, as detected by conventional
      morphology and acquisition of CD15. In contrast to ATRA, GCSF increased Gm colony
      size but not numbers in semi-solid cultures of normal marrow MNC, which suggests
      the cytokine augments post-progenitor amplification. This would explain why GCSF
      increased cell yields in liquid cultures of normal and MDS MNC while GmCFC
      accumulation remained unchanged. GCSF, though, increased Gm colony numbers in
      semi-solid cultures of MDS marrow MNC (P=0.014) so that 4/10 patients now grew
      colonies within the normal range. This was again probably due to increasing clone
      size, so that some clusters, the numbers of which may be elevated in MDS, were
      now scored as colonies. Overall, these data indicate that ATRA can enhance the
      maturation of the progeny of MDS GmCFC whilst GCSF can augment their
      amplification.

PMID- 9619916
TI  - Multidrug-resistant acute leukemia cells are responsive to prolonged exposure of
      daunorubicin: implications for liposome-encapsulated daunorubicin.
AB  - We examined the cytotoxic effects of free daunorubicin (DNR) and liposome
      encapsulated DNR on multidrug-resistant (MDR1) leukemia cells of patients with
      acute leukemias who had failed primary induction treatment that included DNR.
      This was analyzed ex-vivo with DNR concentrations and exposure times that
      normally can be achieved in-vivo for both drugs with induction treatment. The
      leukemic blasts of patients both with drug-resistant AML and drug-resistant ALL
      were, ex-vivo, very sensitive to DNR concentrations and exposure times that can
      be achieved in-vivo by liposome-encapsulated DNR. However, under identical
      conditions, free DNR and liposome-encapsulated DNR had a similar cytotoxic
      profile, arguing against a unique mechanism of cytotoxicity by the liposomal
      constructure. These data suggest that liposome-encapsulated DNR may be preferable
      to free DNR for the treatment of acute leukemias.

PMID- 9619917
TI  - Accelerated entry into S phase associated with up-regulation of cyclin D1 as a
      mechanism for granulocyte colony-stimulating factor (G-CSF)-induced apoptosis of
      murine myeloid leukemia cells.
AB  - We previously reported that injection of recombinant granulocyte colony
      stimulating factor (G-CSF) suppressed the development of leukemia in mice
      transplanted with C2M-A5 (C2M) myeloid leukemia cells and that the anti-leukemic
      effect of G-CSF was ascribed to the induction of apoptosis of C2M cells. These
      observations make a striking contrast with other previous reports on the
      biological activities of G-CSF. In the present study, in order to further clarify
      the G-CSF-induced apoptosis of C2M cells, we studied the effects of G-CSF on the
      cell cycle as well as the molecular events involving D-type cyclines and their
      cyclin-dependent kinases (cdk) in G-CSF-treated C2M cells. Cell cycle analysis
      revealed that G-CSF treatment of C2M cells resulted in accelerated entry from the
      first gap (G1) phase into the DNA synthesis (S) phase. Western blotting disclosed
      that G-CSF treatment resulted in down-regulation of cyclin D2 and cdk2 and up
      regulation of cyclin D1 and cdk4. The reciprocal relationship between the up
      regulation of cyclin D1 and down-regulation of cyclin D2 was closely associated
      with accelerated entry into S phase and subsequent apoptosis of C2M cells. These
      results suggest that G-CSF-induced apoptosis of C2M cells might be ascribed to
      imbalanced cell cycle progression due to deregulated expression of D-type cyclins
      and their cdks.

PMID- 9619919
TI  - Taxol can induce phosphorylation of BCL-2 in multiple myeloma cells and
      potentiate dexamethasone-induced apoptosis.
AB  - We investigated the in vitro effects of paclitaxel (taxol) on multiple myeloma
      (MM) cells. A dose- and time-dependent induction of BCL-2 phosphorylation and
      apoptosis was detected in MM cell lines and two fresh clinical samples obtained
      from patients. A p170-overexpressing MM line and a line that did not express BCL
      2 were resistant. Since phosphorylation of BCL-2 inactivates its anti-apoptotic
      function and could theoretically sensitize MM cells to other agents, we tested
      combinations of taxol and dexamethasone. Only concentrations of taxol that
      phosphorylated BCL-2 interacted with dexamethasone for enhanced apoptotic death.
      Geldanamycin, which prevented taxol-induced BCL-2 phosphorylation, also prevented
      the potentiated cytotoxicity.

PMID- 9619918
TI  - IL-2-induced growth of CD8+ T cell prolymphocytic leukemia cells mediated by NF
      kappaB induction and IL-2 receptor alpha expression.
AB  - The binding of interleukin-2 (IL-2) to its receptor on normal T cells induces
      nuclear expression of nuclear factor kappaB (NF-kappaB), activation of the IL-2
      receptor (IL-2R) alpha chain gene, and cell proliferation. In the present study,
      the role of IL-2R signaling in the growth of CD8+ T cell prolymphocytic leukemia
      (T-PLL) cells has been investigated. Flow cytometry revealed that primary
      leukemia cells from a patient with CD8+ T-PLL expressed IL-2Ralpha and beta
      chains, and the cells showed a proliferative response and an increase in IL
      2Ralpha expression on culture with exogeneous IL-2. Northern blot analysis failed
      to detect IL-2 mRNA, suggesting that IL-2 may act in a paracrine manner in vivo.
      Electrophoretic mobility-shift assays revealed that recombinant IL-2 increased NF
      kappaB binding activity in nuclear extracts of the leukemia cells, and Northern
      blot analysis showed that IL-2 increased the abundance of mRNAs encoding the NF
      kappaB components c-Rel and KBF1 in these cells. IL-2 binding analysis
      demonstrated that IL-2 markedly increased the number of low affinity IL-2Rs on
      the leukemia cells, without an effect on the number of high-affinity IL-2Rs.
      These results show that IL-2 is capable of inducing the nuclear expression of NF
      kappaB in primary CD8+ T-PLL cells, and that this effect is mediated, at least in
      part, at a pretranslational level.

PMID- 9619920
TI  - Rapid evolution of multiple myeloma after cobalamin therapy for megaloblastic
      erythropoiesis with macrocytic anemia.

PMID- 9619921
TI  - Leukaemia and sudden death.

PMID- 9619922
TI  - Migration and wear of long-term successful Charnley total hip replacements.
AB  - We analysed in-vivo migration and wear over a long period of all-polyethylene
      acetabular cups which had not been affected by mechanical loosening. The
      selection criteria of regular radiological follow-up, good clinical outcome
      (Charnley score of 5 or 6), continued walking without crutches and no
      radiological signs of loosening of the acetabular cups were fulfilled by 25
      Charnley total hip arthroplasties. Mean migration, measured by the Nunn method,
      was 0.6 mm in the medial and 0.2 mm in the cranial direction. The mean yearly
      rate of wear was 0.05 mm and 0.04 mm, with six and two cups having no detectable
      wear, as measured by the Livermore and Charnley-Cupic methods, respectively. The
      maximal detected wear was 3.7 mm. There were no changes in the rate of wear with
      time. Computerised Ein Bild Rontgen Analyse (single-image radiological analysis)
      measurements of 20 hips indicated plastic deformation of the cups. We conclude
      that long-term successful cups do not migrate and have a very low rate of wear
      which was not affected by ageing of the polyethylene. There was no evidence that
      polyethylene wear alone caused mechanical loosening of the cup but high rates of
      wear seem to have an adverse prognostic value in terms of the long-term survival
      of the prosthesis.

PMID- 9619923
TI  - The value of preoperative planning for total hip arthroplasty.
AB  - To analyse the value and accuracy of preoperative planning for total hip
      replacement (THR) we digitised electronically and compared the hand-sketched
      preoperative plans with the pre- and postoperative radiographs of 100 consecutive
      primary THRs. The correct type of prosthesis was planned in 98%; the agreement
      between planned and actually used components was 92% on the femoral side and 90%
      on the acetabular side. The mean (+/- SD) absolute difference between the planned
      and actual position of the centre of rotation of the hip was 2.5 +/- 1.1 mm
      vertically and 4.4 +/- 2.1 mm horizontally. On average, the inclination of the
      acetabular component differed by 7 +/- 2 degrees and anteversion by 9 +/- 3
      degrees from the preoperative plans. The mean postoperative leg-length difference
      was 0.3 +/- 0.1 cm clinically and 0.2 +/- 0.1 cm radiologically. More than 80% of
      intraoperative difficulties were anticipated. Preoperative planning is of
      significant value for the successful performance of THR.

PMID- 9619924
TI  - Acetabular reconstruction with impacted morsellised cancellous bone graft and
      cement. A 10- to 15-year follow-up of 60 revision arthroplasties.
AB  - We report a long-term review of 60 acetabular components revised using impacted,
      morsellised bone allografts and a cemented polyethylene cup. The acetabular
      defects were cavitary (37) or combined (23). Follow-up was for a mean 11.8 years
      (10 to 15). Further revision was needed in five hips, two for septic and three
      for aseptic loosening. The overall survival rate at 11.8 years was 90%; excluding
      the septic cases it was 94%. Acetabular reconstruction with impacted morsellised
      cancellous grafts and cement gives satisfactory long-term results.

PMID- 9619925
TI  - Survival analysis of the Harris-Galante I acetabular cup.
AB  - We reviewed 264 consecutive primary total hip replacements in 244 patients in
      which the Harris-Galante I porous-coated acetabular component had been used. The
      mean follow-up was 95 months (69 to 132). In 221 arthroplasties a 32 mm ceramic
      head had been used, and in the other 43 one of cobalt-chrome alloy. There were
      124 women and 120 men with a mean age at operation of 56.8 years (21 to 83).
      Survival analysis of the acetabular components was performed using the following
      definitions of failure: 1) infection; 2) removal because of aseptic loosening; 3)
      removal for any cause; and 4) a worst-case analysis including removal of the cup
      or infection or loss to follow-up. Two well-fixed cups had been removed because
      of deep infection and three, similarly sound cups had been exchanged at the time
      of femoral revision. None of the acetabular components had required revision for
      aseptic loosening. After 11 years survival was 97.7% using the worst-case
      criterion. Radiological analysis of 187 acetabular components at a mean of 82
      months (41 to 132) revealed no case of aseptic loosening. Pelvic osteolysis was
      seen in only one patient, but was not progressive and showed signs of regression.
      The results using these acetabular components are encouraging but the need for
      regular follow-up remains since complications such as significant wear of the
      liner, massive osteolysis of the pelvis, aseptic loosening and late infection may
      increase in the second decade.

PMID- 9619926
TI  - The Metal-Cancellous Cementless Lubeck total hip arthroplasty. Five-to-nine-year
      results.
AB  - We implanted 51 Metal-Cancellous Cementless Lubeck (MCCL) prostheses into 45
      patients with dysplastic hips and followed 49 hips (96.1%) for five to nine
      years. One had needed revision for stem fracture and one for infection; the
      clinical outcome of the other 47 hips was assessed using the Merle d'Aubigne and
      Postel hip score. All hips were either excellent (63%) or good (37%). Three
      patients (6%) had mild thigh pain at six months, but this had settled within two
      years. Serial radiographs showed stable fixation with bone ingrowth in all hips,
      with increased density of the cancellous bone in contact with the implant and
      some trabecular ingrowth. There was early varus shift of the stem in one hip, but
      this stabilised in three months. Osteolysis of the femoral cortex was seen in one
      hip at seven years after surgery, and mild bone resorption due to stress
      shielding in 31 (63%). Acetabular bone grafting with autogenous bone from the
      femoral head gave successful support to the socket in 13 hips. The MCCL
      prosthesis gave satisfactory mid-term results in patients with osteoarthritis
      secondary to hip dysplasia.

PMID- 9619927
TI  - The protective effect of a cut-resistant glove liner. A prospective, randomised
      trial.
AB  - We performed a prospective, randomised study comparing the rates of glove
      perforation using double latex gloving with or without a disposable protective
      glove liner (Paraderm) on 118 patients undergoing primary or revision
      arthroplasty of the hip or knee by one surgeon (FRH). The patients were randomly
      allocated into two groups: in group 1 an inner and outer pair of latex gloves
      were worn as double gloves and in group 2 the glove liner was worn between the
      two latex gloves. There was glove perforation in at least one outer glove in 99
      operations (84%). The operating surgeon was aware of the perforation in 21 of
      these. There were 22 perforations of the inner glove. Group 1 had a significantly
      higher perforation rate per operation (p < 0.05) than group 2. Our findings show
      that protective glove liners significantly reduce the rate of perforation of the
      inner glove during hip and knee arthroplasty.

PMID- 9619928
TI  - Tantalum ball position after total hip arthroplasty.
AB  - There are several techniques for the accurate measurement of the migration of
      components after arthroplasty some of which require the operative placement of
      tantalum balls. We have reviewed the position and migration of these markers in
      64 patients after total hip arthroplasty. In 40% of cases, one or more balls was
      seen to be outside the proximal femur on the postoperative radiograph, although
      all were considered to be within the bone at operation. In two hips, one ball
      appeared to have migrated towards the joint, although none was seen within the
      joint. Misplacement was not related to the experience of the surgeon or the
      operative approach. Migration analysis which necessitates the insertion of
      tantalum balls requires careful technique to avoid a potential source of third
      body wear. It should probably be used only for research in small series of
      patients.

PMID- 9619929
TI  - Hydroxyapatite augmentation of the porous coating improves fixation of tibial
      components. A randomised RSA study in 116 patients.
AB  - In a single-blind, randomised series of knee replacements in 116 patients, we
      used radiostereometric analysis (RSA) to measure micromotion in three types of
      tibial implant fixation for two years after knee replacement. We compared
      hydroxyapatite-augmented porous coating, porous coating, and cemented fixation of
      the same design of tibial component. At one to two years, porous-coated implants
      migrated at a statistically significantly higher rate than hydroxyapatite
      augmented or cemented implants. There was no significant difference between
      hydroxyapatite-coated and cemented implants. We conclude that hydroxyapatite
      augmentation may offer a clinically relevant advantage over a simple porous
      coating for tibial component fixation, but is no better than cemented fixation.

PMID- 9619930
TI  - Pain in the assessment of total knee replacement.
AB  - The results of total knee replacement (TKR) are commonly assessed by survival
      analysis using revision as the endpoint. We have used the assessment of pain by a
      patient-based questionnaire as an alternative. In one hospital, 1429 TKRs were
      inserted by 66 surgeons between 1987 and 1993. The survival at seven years, with
      revision as the endpoint, was 97.5% (CI 94 to 100). There were no significant
      differences between the three different types of implant used, the AGC, the IB2
      and the Nuffield Knee. When the endpoint was the development of moderate pain,
      the survival at seven years for the AGC knee was 72% and that for the IB2 was
      similar. Significantly more patients (p = 0.007) with the Nuffield Knee, however,
      had developed moderate pain. Using revision as the endpoint, it is difficult to
      discriminate between the various types of TKR, but this can be achieved using
      pain. In this investigation 30% of the patients reported moderate pain at some
      stage by seven years from operation.

PMID- 9619931
TI  - The influence of osteoporosis on varus osteoarthritis of the knee.
AB  - We studied 37 patients with varus osteoarthritis of the knee to determine the
      influence of the bone mineral density (BMD) on the varus deformity. There were 15
      men (21 knees) and 22 women (38 knees). The mean age of the men was 69 years and
      of the women 68 years. BMD was measured in the L1-L4 spinal region using dual X
      ray absorptiometry. In the women a low level of BMD was associated with varus
      deformity originating at the proximal tibia, but a high level was predominantly
      linked with deformity originating in the joint space. Similar findings were
      obtained in the men. Our results suggest that a low BMD predisposes to trabecular
      microfractures and consequently increased stress on the articular cartilage. A
      low BMD does not preclude osteoarthritic change in the knee.

PMID- 9619932
TI  - Clinical and pathological changes in the knee after accidental chlorhexidine
      irrigation during arthroscopy. Case reports and review of the literature.
AB  - We describe six knees in five patients, referred to us after accidental
      irrigation with chlorhexidine 1% in aqueous solution during arthroscopy. All six
      knees developed persisting pain, swelling and crepitus with loss of range of
      movement. Radiographs showed loss of joint space in all three compartments due to
      extensive chondrolysis, with many loose bodies and synovitis. Histological
      examination showed partial necrosis of the cartilage, with slight non-specific
      inflammation and fibrosis of synovial specimens. Care is needed in checking
      irrigation fluids, and these should have a distinctive colour.

PMID- 9619933
TI  - Evaluation of fluorodeoxyglucose positron emission tomography in the management
      of soft-tissue sarcomas.
AB  - We performed a retrospective analysis to evaluate the ability of whole-body F
      fluorodeoxyglucose positron emission tomography (FDG PET) to identify local
      recurrence and pulmonary metastases in patients with soft-tissue tumours after
      treatment. We compared the results of FDG PET with those of MRI for the detection
      of local recurrence, and with CT of the chest for pulmonary metastases. We
      assessed 62 patients of mean age 51 years, who had 15 types of soft-tissue
      sarcoma, after a mean follow-up of 3 years 2 months. For the detection of local
      disease, 71 comparisons showed that the sensitivity and specificity of FDG PET
      were 73.7% and 94.3%, respectively; there were 14 true-positive and five false
      negative results. MRI had a sensitivity and specificity of 88.2% and 96.0%
      respectively. For the identification of lung metastases, 70 comparisons showed
      that the sensitivity and specificity of FDG PET were 86.7% and 100%, with 13 true
      positive results and two false-negative results. CT of the chest had a
      sensitivity and specificity of 100% and 96.4%. Thirteen other sites of metastases
      were identified by FDG PET. FDG PET can identify both local and distant
      recurrence of tumour as a one-step procedure and will detect other metastases. It
      seems that all three methods of imaging are needed to define accurately the
      extent of disease, both at initial staging and during follow-up.

PMID- 9619934
TI  - Aortic pseudoaneurysm in the L3-L4 disc space after lumbar disc surgery. A case
      report.
AB  - We report a patient who developed an aortic pseudoaneurysm in the L3-L4 disc
      space after lumbar disc surgery. The diagnosis was made by MRI and aortography,
      and repair using a prosthetic graft and anterior fusion was successful. We
      discuss the predisposing factors, the clinical picture and management of vascular
      injuries during disc excision.

PMID- 9619935
TI  - Treatment of type-two odontoid fractures in halothoracic vests.
AB  - We treated 22 patients with type-two odontoid fractures in halothoracic vests for
      six to eight weeks followed by a Philadelphia collar for four weeks. Eighteen
      patients were reviewed by questionnaire and radiography at a mean of 40 months
      after injury. We assessed union, fracture position, the degree of permanent pain
      and stiffness, satisfaction with the treatment and the outcome. The overall union
      rate was 82%. Posterior malunion with residual posterior displacement or
      angulation was associated with a higher incidence of persisting pain. The
      position at union did not correlate with the residual cervical stiffness.
      Fractures failed to unite in four patients (18%) none of whom had late
      neurological sequelae, although they had more late pain. There were associations
      between the development of nonunion and an extension-type injury, age over 65
      years and delay in diagnosis.

PMID- 9619936
TI  - A 15-year assessment of controlled trials of the management of tuberculosis of
      the spine in Korea and Hong Kong. Thirteenth Report of the Medical Research
      Council Working Party on Tuberculosis of the Spine.
AB  - The final results up to 15 years are reported of clinical trials of the
      management of tuberculosis of the spine in Korea and Hong Kong. In Korea, 350
      patients with active spinal tuberculosis were randomised to ambulatory
      chemotherapy or bed rest in hospital (in Masan) or a plaster-of-Paris jacket for
      nine months (in Pusan). Patients in both centres were also randomised to either
      PAS plus isoniazid for 18 months or to the same drugs plus streptomycin for the
      first three months. In Hong Kong, all 150 patients were treated with the three
      drug regime and randomised to either radical excision of the spinal lesion with
      bone graft or open debridement. On average, the disease was more extensive in
      Korea, but at 15 years (or 13 or 14 years in a proportion of the patients in
      Korea) the great majority of patients in both countries achieved a favourable
      status, no evidence of CNS involvement, no radiological evidence of disease, no
      sinus or clinically evident abscess, and no restriction of normal physical
      activity. Most patients had already achieved a favourable status much earlier.
      The earlier results of these trials are confirmed by the long-term follow-up with
      no late relapse or late-onset paraplegia. The results of chemotherapy on an
      outpatient basis were not improved by bed rest or a plaster jacket and the only
      advantage of the radical operation was less late deformity compared with
      debridement. A second series of studies has shown that short-course regimes based
      on isoniazid and rifampicin are as effective as the 18-month regimes: ambulatory
      chemotherapy with these regimes should now be the main management of
      uncomplicated spinal tuberculosis.

PMID- 9619937
TI  - MRI high-signal intensity in the menisci of asymptomatic children.
AB  - We reviewed retrospectively the MRI examinations of 108 knees of 80 children to
      identify the prevalence of a high signal in the menisci of those without
      symptoms. There were 51 boys and 29 girls with a mean age of 12.2 years (8 to
      15). The prevalence of a high signal within the menisci was 66%, significantly
      higher than that in an adult group (29%). The prevalence decreased with age:
      grade-2 and grade-3 changes were observed in 80% of menisci at ten years of age,
      in 65% at 13 years and in 35% at 15 years. The prevalence of high signals also
      decreased with increased skeletal maturity at the knee. We emphasise the
      importance of awareness of the high prevalence of a high signal intensity in the
      menisci of children, especially in early adolescence.

PMID- 9619938
TI  - Neuropathic arthropathy of the knee associated with an intra-articular
      neurofibroma in a child.
AB  - We describe a five-year-old child with neurofibromatosis type I who developed a
      Charcot knee. Infiltration of the joint by tissue associated with the disease
      caused damage to the proprioceptive mechanism and resulted in severe joint
      instability, accelerated destruction and development of neuropathic arthropathy.

PMID- 9619939
TI  - Reduced incidence of septic arthritis in children by Haemophilus influenzae type
      b vaccination. Implications for treatment.
AB  - In many countries Haemophilus influenzae type b (Hib) is the second most common
      cause of septic arthritis in children. In Finland large-scale immunisation
      against Hib using conjugate vaccines began in 1986, four years after a
      multicentre prospective study of orthopaedic infections in children had started.
      Since 1982, including six years before and ten after starting routine Hib
      vaccination, there has been a major change in the pattern of septic arthritis.
      From 1982 to 1988, 32 of 61 cases (53%) were caused by staphylococci, 22 (36%) by
      Hib and 7 (11%) by other bacteria. Since 1988, Hib infection has disappeared, and
      one-third of cases of childhood septic arthritis has been eliminated. This change
      has allowed us to reduce initial antimicrobial therapy for such children to cover
      only Gram-positive cocci. The more limited treatment is safer, reduces cost, and
      simplifies treatment.

PMID- 9619940
TI  - A new test for estimating iliotibial band contracture.
AB  - Contracture of the iliotibial band leading to flexion and abduction deformity at
      the hip is common in residual paralysis after polio. Ober's test has been used to
      detect this, but it is unreliable and cannot determine the degree of contracture.
      We describe a new test which quantifies this contracture and can be used for
      comparative purposes.

PMID- 9619941
TI  - Fractures of the clavicle in the adult. Epidemiology and classification.
AB  - From 1988 to 1994 a consecutive series of 1000 fractures of the adult clavicle
      was treated in the Orthopaedic Trauma Clinic of the Royal Infirmary of Edinburgh.
      In males, the annual incidence was highest under 20 years of age, decreasing in
      each subsequent cohort until the seventh decade. In females, the incidence was
      more constant, but relatively frequent in teenagers and the elderly. In young
      patients, fractures usually resulted from road-traffic accidents or sport and
      most were diaphyseal. Fractures in the outer fifth were produced by simple
      domestic falls and were more common in the elderly. A new classification was
      developed based on radiological review of the anatomical site and the extent of
      displacement, comminution and articular extension. There were satisfactory levels
      of inter- and intraobserver variation for reliability and reproducibility.
      Fractures of the medial fifth (type 1), undisplaced diaphyseal fractures (type
      2A) and fractures of the outer fifth (type 3A) usually had a benign prognosis.
      The incidence of complications of union was higher in displaced diaphyseal (type
      2B) and displaced outer-fifth (type 3B) fractures. In addition to displacement,
      the extent of comminution in type-2B fractures was a risk factor for delayed and
      nonunion.

PMID- 9619942
TI  - Reamed versus unreamed femoral nails. A randomised, prospective trial.
AB  - We performed a randomised, prospective trial to evaluate the use of unreamed
      titanium nails for femoral fractures. Of 48 patients with 50 femoral fractures 45
      were followed to union; 23 with an unreamed and 22 with a reamed nail. The study
      was stopped early because of a high rate of implant failure. The fractures in the
      unreamed group were slower to unite (39.4 weeks) than those in the reamed group
      (28.5 weeks; p = 0.007). The time to union was over nine months in 57% of the
      unreamed group and in 18% of the reamed group. In the unreamed group 14 secondary
      procedures were required in ten patients to enhance healing compared with three
      in three patients in the reamed group. Six implants (13%) failed, three in each
      group. Four of these six fractures showed evidence of delayed union. To achieve
      quicker union and fewer implant failures we recommend the use of reamed nails of
      at least 12 mm in diameter for female patients and 13 mm in males.

PMID- 9619943
TI  - Reconstruction of the coronoid for chronic dislocation of the elbow. Use of a
      graft from the olecranon in two cases.
AB  - Persistent dislocation of the elbow after a fracture of the coronoid process is a
      difficult problem. We have performed an open reduction with reconstruction of the
      coronoid by an osteocartilaginous graft from the ipsilateral olecranon for two
      patients. Both achieved a painless, stable joint with a functional range of
      movement. The joint surface of the graft has a similar curve to that of the
      coronoid giving good congruency and stability. The technique is simple and the
      graft is obtained through the same incision.

PMID- 9619944
TI  - A new provocative test for carpal tunnel syndrome. Assessment of wrist flexion
      and nerve compression.
AB  - To establish the value of median nerve compression with wrist flexion as a
      provocative test for carpal tunnel syndrome (CTS), we performed a prospective
      study of 64 patients (95 hands) with CTS confirmed by electrodiagnostic studies
      and 50 normal subjects (96 hands). We recorded results for the common provocative
      tests (Tinel's percussion test, Phalen's wrist flexion test and the carpal
      compression test) and the new test which combines wrist flexion with median nerve
      compression. Using a receiver operator characteristic curve (ROC) technique, we
      found that the optimal cut-off time for the wrist-flexion and median-nerve
      compression test was 20 s, giving a sensitivity of 82% and a specificity of 99%.
      These results were significantly better than for Phalen's wrist flexion test (61%
      and 83%, respectively) and for the sensitivity of Tinel's test (74%). The
      positive predictive values of the wrist flexion and median-nerve compression
      test, which is more important clinically, were 99%, 95% and 81% at population
      prevalences of 50%, 20% and 5%, respectively. These were significantly better
      than those of the three other provocative tests at each prevalence.
      Electrodiagnostic studies have significant false-positive and false-negative
      rates in CTS, and therefore provocative tests remain important in its diagnosis.
      We have shown that wrist flexion combined with the median-nerve compression test
      at 20 s, is significantly better than the other methods, and may thus be
      clinically useful.

PMID- 9619945
TI  - Pain relief after nerve resection for post-traumatic neuralgia.
AB  - We performed resection of part of an injured peripheral nerve in 20 patients with
      post-traumatic neuralgia, after conservative treatment had failed. All had
      burning pain, paraesthesia and dysaesthesia in the area innervated by the injured
      nerve. We resected the nerve in the area in which the patient felt pain, and a
      further 3 cm proximal to the site of injury. In all cases, the local pain
      disappeared or markedly decreased. The areas of pain relief and of nerve
      resection coincided completely in 17 patients and partially in three. The results
      were assessed as excellent by five patients, good by 11, and fair by four. There
      were no poor results. Histological examination of the resected nerves showed
      Wallerian degeneration and immunohistochemical tests indicated that substance P,
      a polypeptide which may contribute to nociceptive transmission, was present in
      the tissue around the degenerated nerves.

PMID- 9619946
TI  - Denervation of the radiocarpal joint. A follow-up study in 22 patients.
AB  - Denervation surgery has been a mainstay of our management of chronic pain in the
      wrist. If there is useful movement at the wrist we prefer denervation to
      arthrodesis. We have reviewed 22 patients at a mean of 50 months after such
      denervation surgery at the wrist. This was the only treatment in 16 patients; the
      other six also had other treatments. Pain was reduced in 16 patients, and 17 were
      satisfied or improved. None of the patients wished to have a supplementary
      arthrodesis. We stress the importance of preoperative blockade tests and of a
      very detailed knowledge of the local anatomy.

PMID- 9619947
TI  - First metacarpal osteotomy for trapeziometacarpal osteoarthritis.
AB  - We report a long-term follow-up of abduction-extension osteotomy of the first
      metacarpal, performed for painful trapeziometacarpal osteoarthritis. Of a
      consecutive series of 50 operations, 41 thumbs (82%) were reviewed at a mean
      follow-up of 6.8 years. Good or excellent pain relief was achieved in 80%, and
      93% considered that surgery had improved hand function, while 82% had normal grip
      and pinch strength, with restoration of thumb abduction. Metacarpal osteotomy was
      equally successful in relieving symptoms of those with early (grade 2) and
      moderate (grade 3) degenerative changes. This simple procedure provides lasting
      pain relief, corrects adduction contracture and restores grip and pinch strength,
      giving good results with few complications.

PMID- 9619948
TI  - Incidence and clinical significance of bone bruises after supination injury of
      the ankle. A double-blind, prospective study.
AB  - We used MRI to study a prospective series of 95 patients with inversion injuries
      of the ankle and no fracture on plain radiographs. We found an incidence of bone
      bruises of 27%, but these made no difference to the time of return to work,
      limitation of walking or physical activity, or the clinical outcome scores at
      three months. We conclude that bone bruises have very little clinical
      significance after inversion injuries of the ankle.

PMID- 9619949
TI  - Chevron osteotomy of lesser metatarsals for intractable plantar callosities.
AB  - We performed distal chevron osteotomy of the second, third, or fourth metatarsal
      for painful plantar callosities in 19 non-rheumatoid patients (16 women, 3 men;
      21 feet); their mean age was 59 years (32 to 85). The mean follow-up was four
      years (2 to 7). The overall results were good in 16 feet, fair in two, and poor
      in three, with four patients still having painful plantar callosities. There was
      union in all feet, but transfer metatarsalgia developed in three and three
      required an orthosis. Distal chevron osteotomy for intractable plantar
      callosities was successful both clinically and radiologically in most patients.

PMID- 9619950
TI  - The prevention of peridural adhesions. A comparative long-term histomorphometric
      study using a biodegradable barrier and a fat graft.
AB  - We studied peridural fibrosis in 16 dogs after laminectomies at the L2, L4 and L6
      levels. They received either a free fat graft, a biodegradable mechanical barrier
      (polyethylene oxide (PEO)/polybutylene terephthalate (PBT) copolymer), or no
      treatment. The animals were killed after 4, 12, 26 and 52 weeks. Histomorphometry
      showed extensive and consistent peridural fibrosis in control and PEO/PBT groups.
      Fat grafts produced significantly less fibrous tissue, but the presence of the
      fat graft in the bony defect prevented closure. Degradation of the PEO/PBT
      barrier resulted in the formation of more fibrous tissue. We conclude that up to
      one year a free fat graft is effective in reducing the amount of peridural
      scarring.

PMID- 9619951
TI  - Treatment of osteomyelitis with antibiotic-soaked porous glass ceramic.
AB  - We have developed a new drug delivery system using porous apatite-wollastonite
      glass ceramic (A-W GC) to treat osteomyelitis. A-W GC (porosity, 70% and 20% to
      30%), or porous hydroxyapatite (HA) blocks (porosity 35% to 48%) used as
      controls, were soaked in mixtures of two antibiotics, isepamicin sulphate (ISP)
      and cefmetazole (CMZ) under high vacuum. We evaluated the release concentrations
      of the antibiotics from the blocks. The bactericidal concentration of ISP from A
      W GC was maintained for more than 42 days, but that from HA decreased to below
      the detection limit after 28 days. The concentrations of CMZ from both materials
      were lower than those of ISP. An in vivo study using rabbit femora showed that an
      osseous concentration of ISP was maintained at eight weeks after implantation.
      Osteoconduction of the A-W GC block was good. Four patients with infected hip
      arthroplasties and one with osteomyelitis of the tibia have been treated with the
      new delivery system with excellent results.

PMID- 9619952
TI  - Cellular profile and cytokine production at prosthetic interfaces. Study of
      tissues retrieved from revised hip and knee replacements.
AB  - The tissues surrounding 65 cemented and 36 cementless total joint replacements
      undergoing revision were characterised for cell types by immunohistochemistry and
      for cytokine expression by in situ hybridisation. We identified three distinct
      groups of revised implants: loose implants with ballooning radiological
      osteolysis, loose implants without osteolysis, and well-fixed implants. In the
      cemented series, osteolysis was associated with increased numbers of macrophages
      (p = 0.0006), T-lymphocyte subgroups (p = 0.03) and IL-1 (p = 0.02) and IL-6 (p =
      0.0001) expression, and in the cementless series with increased numbers of T
      lymphocyte subgroups (p = 0.005) and increased TNF alpha expression (p = 0.04).
      For cemented implants, the histological, histochemical and cytokine profiles of
      the interface correlated with the clinical and radiological grade of loosening
      and osteolysis. Our findings suggest that there are different biological
      mechanisms of loosening and osteolysis for cemented and cementless implants. T
      lymphocyte modulation of macrophage function may be an important interaction at
      prosthetic interfaces.

PMID- 9619953
TI  - Iron deposits and catabolic properties of synovial tissue from patients with
      haemophilia.
AB  - Haemophilic arthropathy is characterised by iron deposits in synovial tissues. We
      investigated the suggestion that iron plays an important role in synovial
      changes. We obtained synovial tissue from six patients with haemophilia during
      arthroplasty, finding that brown haemosideritic tissue was often adjacent to
      tissue with a macroscopically normal appearance in the same joint. Samples from
      both types of synovial tissue were analysed histologically and biochemically to
      determine catabolic activity. Macroscopically haemosideritic synovium showed a
      significantly higher inflammatory activity than that with a normal appearance.
      Cultures of abnormal synovial tissue gave a significantly enhanced production of
      IL-1, IL-6 and TNF alpha compared with cultures of synovial tissue with a normal
      appearance. In addition, the supernatant fluids from the cultures showed greater
      catabolic activity from haemosideritic tissue, as determined by the inhibition of
      the synthesis of articular cartilage matrix. We conclude that in patients with
      haemophilic arthropathy, local synovial iron deposits are associated with
      increased catabolic activity.

PMID- 9619954
TI  - Dose-related effects of shock waves on rabbit tendo Achillis. A sonographic and
      histological study.
AB  - We aimed to determine whether extracorporeal shock waves of varying intensity
      would damage the intact tendo Achillis and paratenon in a rabbit model. We used
      42 female New Zealand white rabbits randomly divided into four groups as follows:
      group a received 1000 shock-wave impulses of an energy flux density of 0.08
      mJ/mm2, group b 1000 impulses of 0.28 mJ/mm2, group c 1000 impulses of 0.60
      mJ/mm2, and group d was a control group. Sonographic and histological evaluation
      showed no changes in group a, and transient swelling of the tendon with a minor
      inflammatory reaction in group b. Group c had formation of paratendinous fluid
      with a significant increase in the anteroposterior diameter of the tendon. In
      this group there were marked histological changes with increased eosin staining,
      fibrinoid necrosis, fibrosis in the paratenon and infiltration of inflammatory
      cells. We conclude that there are dose-dependent changes in the tendon and
      paratenon after extracorporeal shock-wave therapy and that energy flux densities
      of over 0.28 mJ/mm should not be used clinically in the treatment of tendon
      disorders.

PMID- 9619955
TI  - The behavioural response to whiplash injury.

PMID- 9619956
TI  - Neurological deterioration after posterior wiring of the cervical spine.

PMID- 9619957
TI  - Fractures of the base of the middle phalanx of the finger.

PMID- 9619958
TI  - MRI after operative reduction for developmental dysplasia of the hip.

PMID- 9619959
TI  - Fracture on removal of the ACE tibial nail.

PMID- 9619960
TI  - A locking nail for fractures of the humerus.

PMID- 9619961
TI  - Reamed or unreamed tibial nailing for closed tibial fractures.

PMID- 9619962
TI  - Closed treatment of displaced middle-third fractures of the clavicle gives poor
      results.

PMID- 9619963
TI  - Multimorbidity in general practice: prevalence, incidence, and determinants of co
      occurring chronic and recurrent diseases.
AB  - Increasing numbers of people are found to have two or more diseases at the same
      time, which is termed multimorbidity. We studied the prevalence, incidence, and
      determinants of multimorbidity and the statistical clustering of chronic and
      recurrent diseases in a general practice setting. Prevalence of multimorbidity
      increased with all age groups from 10% in the 0-19-year-old age group up to 78%
      in subjects aged 80 and over. Increasing age, lower level of education, and
      public health insurance were related to the occurrence of morbidity, but even
      more strongly to the occurrence and degree of multimorbidity. The one-year
      incidence of multimorbidity (the new occurrence of two or more diseases in one
      year) was related to increasing age, public health insurance, and the presence of
      prevalent diseases at baseline. Statistical clustering of diseases was stronger
      than expected, especially among the younger subjects.

PMID- 9619964
TI  - The effect of socio-demographic and crash-related factors on the prognosis of
      whiplash.
AB  - Whiplash injury, common after a motor vehicle crash, has a variable prognosis
      that is difficult to predict. To assess the role of various factors on this
      prognosis, we assembled a historical cohort of 3014 individuals who sustained a
      whiplash injury resulting from a motor vehicle crash in the Province of Quebec,
      Canada, in 1987 and were followed for 6 years. The data were obtained from the
      computerized databases created by the province's universal automobile insurance
      plan and police accident reports. The recovery time from whiplash, as measured by
      duration of compensation, was the primary outcome. Socio-demographic and crash
      related factors measured at the time of the crash were investigated. The median
      recovery time for the cohort was 31 days, with 22% recovering within a week and
      3% still not recovered after 1 year. For the 1551 subjects with a whiplash injury
      only, the socio-demographic factors that were found to be independently
      associated with a slower recovery from whiplash in this cohort are female gender,
      older age, having dependents, and not having full-time employment. The
      significant crash-related factors are occupancy in a truck or bus, being a
      passenger in the vehicle, colliding with a moving object, and being in a head-on
      or perpendicular collision. We classified the subjects according to a prediction
      score ranging from 0 to 11, devised from these factors. Subjects with a score of
      0 to 2, that is those who had at most two risk factors present, had the fastest
      median recovery time of 19 days compared with 71 days for subjects who had a
      score of 6 or more. We conclude that several sociodemographic and crash-related
      factors are independently associated with a slow and costly recovery from
      whiplash injury. They are easily measurable at the time of the crash and combined
      so as to be simply incorporated in intervention programs aimed at early
      identification and management of whiplash patients with a poor prognosis.

PMID- 9619965
TI  - Blood pressure reduction, cardiovascular diseases, and cognitive decline in the
      mini-mental state examination in a community population of normal very old
      people: a three-year follow-up.
AB  - We observed the decline in cognitive functioning in a community cohort of 924
      persons aged > or =75 years with initially good cognition. Cognitive performance
      was indexed with the Mini-Mental State Examination (MMSE) on two occasions, 3
      years apart. The average decline in MMSE score was 0.4 points per year. However,
      23.4% of the participants lost more than 10% of their baseline MMSE scores. Women
      declined more rapidly than men. Baseline advanced age, lower education, and
      stroke predicted the greater decline in women. It appears that the relation of
      lower education and stroke with cognitive decline was more pronounced in men, but
      age did not predict cognitive decline in men. In addition, there was a
      correlation between systolic pressure reduction and cognitive decline in women,
      which was not accounted for by other factors. In summary, although the cognitive
      ability is generally spared longitudinally, in terms of the entire population, a
      considerable proportion of individuals show substantial decline that is related
      to several factors such as advanced age, female gender, lower education, stroke,
      and systolic pressure reduction.

PMID- 9619966
TI  - Energy adjustment does not control for differential recall bias in nutritional
      epidemiology.
AB  - It has been stated that energy adjustment can control for recall bias in case
      control studies. Simulation of recall bias and cases and controls in a
      nutritional survey of German adults was conducted to examine its impact on five
      dietary effects, (adding a macronutrient, substituting one macronutrient for
      another, adding a macronutrient while keeping the other energy sources constant,
      and changing the macronutrient to energy ratio through addition or substitution)
      using various energy adjustment models. If energy adjustment were an effective
      means of correcting measurement error, the energy adjusted dietary effects, after
      a subtraction of energy and fat intake, should equal those in the original data
      set. Simulation of differential under-reporting of fat and energy intake by cases
      but not controls showed this to dramatically impact all five considered dietary
      effects, even after energy adjustment. The influence of the assumed recall bias
      on the different effects depends on the error type structure, inflating an odds
      ration of 1.8 to as much as 12.3 or reducing it to 0.45 when 100 kcal of fat was
      substituted for 100 kcal of other macronutrients. Although energy adjustment may
      serve many functions, it cannot correct for differential error. Depending upon
      the nature of the hypothesized effect and the error type, energy adjustment may
      also distort risk ratios in the presence of non-differential bias. The concern
      that cases and controls report their energy intakes with different degrees of
      error remains a critical consideration that must be addressed through improved
      measurements, and not energy adjustment under any of the currently used models.

PMID- 9619967
TI  - Maternal recall of distant pregnancy events.
AB  - Women themselves are often the most convenient source of information regarding
      their pregnancy and birth outcomes such as prematurity. However, the ability of
      mothers to recall birth information and the accuracy of information they do
      recall has rarely been assessed. This study used a mail survey of women who
      delivered either term or preterm infants in Rochester, Minnesota, between 1980
      and 1985. Maternal reports of circumstances and outcome of delivery were compared
      to data abstracted from the medical records. Maternal ability to recall and
      report events varied from 99.5% for smoking during pregnancy to 85% for infant's
      gestational age at birth. Agreement between medical record and maternal report
      was very high for perinatal events such as delivery by cesarean section,
      preexisting diabetes, and smoking. Percent negative agreement was quite high when
      comparing information on rare events such as placental abruption. Recall of
      gestational age was better for women delivering preterm infants but uncommon in
      all women. Maternal reports of perinatal events in which they directly
      participated such as cesarean section can be accurately and reliably reported 10
      to 15 years after the birth. Gestational age is reported less accurately and with
      different rates of recall for mothers with term and preterm deliveries.

PMID- 9619968
TI  - Validity of self-reported fat distribution in young adults: the CARDIA Study.
      Coronary Artery Risk Development in Young Adults.
AB  - To determine the validity of self-reported information on body fat distribution,
      relationships between reported location of weight gain and measured waist-to-hip
      ratio (WHR), high density lipoprotein cholesterol (HDL-C), and fasting insulin
      were analyzed in 5115 black and white men and women aged 18-30 years. In black
      men, WHR adjusted for age and body mass index (BMI) ranged from 0.833 among those
      reporting upper and central weight gain to 0.812 among those reporting lower body
      weight gain (trend across five reported fat distribution categories, P = 0.0004).
      Corresponding values were, for white men, 0.852 to 0.831; for black women, 0.777
      to 0.721; and for white women, 0.772 to 0.701 (each P < 0.0001). Reported fat
      distribution was associated with HDL-C in women, but not in men, and with fasting
      insulin in all groups. While these associations were somewhat weaker than with
      measured WHR, self-reported fat distribution does provide valid information about
      body fat distribution in young adults, particularly women.

PMID- 9619969
TI  - Adverse lipid and coronary heart disease risk profiles in young women with
      polycystic ovary syndrome: results of a case-control study.
AB  - Polycystic ovary syndrome (PCOS), a disorder of hyperandrogenism and chronic
      anovulation affects 5%-10% of all women. Women with PCOS often have elevated
      cardiovascular risk factors. A total of 244 PCOS cases were identified through
      the Division of Reproductive Endocrinology at Magee-Womens Hospital and were age
      matched to 244 neighborhood controls. The average age of cases and controls was
      35.3 +/- 7.4 and 36.7 +/- 7.7. Women with PCOS compared to controls had
      substantially higher LDL-C and total cholesterol levels at each age group under
      45 years after adjustment for body mass index, hormone use, and insulin levels.
      In the over 40-year age group, little difference was noted between cases and
      controls. Among cases and controls (<40), PCOS predicted LDL-C, total cholesterol
      and triglycerides, but did not have a significant effect on lipid levels in older
      cases and controls after controlling for the other variables. The primarily pre-
      to perimenopausal PCOS cases > or =40 years of age have similar LDL-C and total
      cholesterol levels as their age-matched controls, probably reflecting the LDL-C
      increase with age among controls.

PMID- 9619970
TI  - Factors associated with serum HCV RNA positivity in anti-HCV antibody positive
      intravenous drug users.
AB  - Serum hepatitis C virus (HCV) RNA, HCV genotypes and liver function tests were
      evaluated in a series of 189 unselected, consecutive anti-HCV positive
      intravenous drug users (IVDUs). Serum HCV RNA was detected in 106/189 patients.
      Abnormal liver function tests were associated with alcohol abuse, but not with
      the presence of serum HCV RNA. Among 109 patients retested after a mean follow-up
      of 21 months, 41 were intermittently serum HCV RNA positive. Patients
      persistently negative had more commonly a past history of acute hepatitis. A
      history of prostitution and/or a pattern of abuse involving >30 injections per
      week were related to infection by genotype 3a. In conclusion, serum HCV RNA is
      either transiently or persistently detectable in most anti-HCV positive IVDUs,
      but bears no association with abnormal liver biochemistry. Infection by HCV-3a is
      more common in IVDUs with more deviant life styles. In those cases where serum
      HCV RNA is found repeatedly negative, HCV infection may have been cleared,
      possibly through an episode of acute hepatitis.

PMID- 9619972
TI  - Averaging attributable fractions in the multifactorial situation: assumptions and
      interpretation.
AB  - In multifactorial situations, the concept of attributable fraction quantifying
      the population impact of exposure factors on the disease load needs special
      methodologic care to take the interrelationship between exposures into account.
      Recently, new epidemiologic parameters have been introduced to address this
      issue. These approaches are reconsidered here from a game-theoretical
      perspective. The derivation of game-theoretical properties of these parameters
      provides additional motivation for their use in epidemiologic practice and offers
      new insights into their interpretation in epidemiologic studies. The nontechnical
      description of the results is illustrated by examples from the Hordaland study on
      obstructive lung disease.

PMID- 9619971
TI  - Evaluating health status of elderly Chinese in Boston.
AB  - There is increasing demand for measurement tools to assess health related quality
      of life among the Chinese elderly population in the United States. Health
      services questionnaires, developed largely in English, often under-represent
      Chinese Americans. Based on conventional mortality statistics, the public
      mistakenly views Chinese Americans as a "model" minority with no health problems.
      This general perception has masked the serious health problems among the elderly
      Chinese Americans. Using the newly developed Chinese version of the MOS SF-36, we
      aim to explore how elderly Chinese perceive their own health. Based on 219
      elderly Chinese recruited in Boston, the study provided mixed results with regard
      to the perception of a healthy minority model. While the study subjects perceived
      similar or better physical health to the U.S. norm, they reported worse mental
      health than the U.S. norm. We explored possible explanations for this discrepancy
      and discussed the implications as well as directions for future research.

PMID- 9619973
TI  - Chevalier Jackson's contributions to direct laryngoscopy.
AB  - Chevalier Jackson championed rigid endoscopy of the upper aerodigestive tract and
      facilitated its development and popularity at the beginning of the 20th century.
      He realized that endoscopy and open surgery are inextricably linked for effective
      management of diseases of the upper air and food passages. Toward this end,
      Jackson contributed a number of important innovations to direct laryngoscopy,
      while developing a unique mastery of the technique. Ultimately, he combined this
      endoscopic proficiency with open surgical techniques.

PMID- 9619974
TI  - Muscle spindles are concentrated in the superior vocalis subcompartment of the
      human thyroarytenoid muscle.
AB  - It is hypothesized that different parts of the thyroarytenoid muscle (TA) are
      functionally specialized. Specifically, the TA is divided into a lateral
      muscularis compartment and a medial vocalis compartment. This study examined the
      distribution of muscle spindles throughout the human TA as an indicator of these
      functional differences. Histological cross-sections from the anterior, middle,
      and posterior regions of five human membranous vocal folds were examined for the
      number and location of muscle spindles. There was an average of 6.1 muscle
      spindles in sections from each region with no significant variation between the
      different regions (p < .05). However, in sections from all three regions, the
      muscle spindles were always found to be concentrated in the superior medial
      quadrant of the TA (mean 85.9%, p < .01). The inferior medial, superior lateral,
      and inferior lateral quadrants of the TA contained 11.96%, 2.17%, and 0%,
      respectively, of the total muscle spindles. Within the superior medial quadrant,
      most of the muscle spindles were localized in the most superficial part of the
      muscle. The results of this study demonstrate that the majority of TA muscle
      spindles are concentrated in its superior medial quadrant, an area we have termed
      the superior vocalis subcompartment (SC). This finding suggests that the superior
      vocalis SC is functionally distinct from the remainder of the TA. It is
      hypothesized that tension in the superior vocalis SC can be controlled
      independently from the remainder of the TA, and this capability is used to effect
      the biomechanics of vocal fold vibration during phonation.

PMID- 9619975
TI  - Spatial arrangement of the structural elements of vocal fold layers: an
      adjustment to the vibration process.
AB  - It is well established that the multilayered structure of the vocal fold is
      highly adjusted to the requirements of the vibration process during phonation.
      There is also some partial data indicating that the spatial arrangement of each
      vocal fold layer corresponds to the functional requirements, and thus facilitate
      the phonation process. Nevertheless, all reports on the spatial arrangement of
      the vocal fold structures deal only with an individual element of the vocal fold
      histologic structure. The present study encompasses the spatial histologic
      analysis of all major elements of the vocal fold layers. It was demonstrated that
      the vocal fold epithelial cells, the connective and muscle fibers, and even the
      blood vessels run parallel to the vocal fold free edge, which indicates a high
      adjustment to the phonation requirements and the vibration process.

PMID- 9619976
TI  - Just noticeable differences for glottal flow waveform characteristics.
AB  - This study was primarily motivated by the need to establish the correspondence
      between auditory abilities and laryngeal function. Just noticeable differences
      (JNDs) were obtained for the open quotient and speed quotient of the glottal flow
      waveform. The quotients were synthesized for both the glottal flow alone, and for
      the output pressure signal after the glottal flow signal was applied to the
      synthesis vocal tract for the vowel /a/. Six adult men and five adult women, all
      teachers of singing, participated as listeners. An adaptive auditory listening
      procedure was used to estimate JNDs for the four types of stimuli. The group
      average JND values were as follows. For the standard open quotient value of
      .6000, JND = 0.0264 (SD = .010) for the glottal flow and JND = 0.0344 (SD = .020)
      for the output pressure. For the open quotient, there was no statistically
      significant difference between genders or between the types of signals. For the
      standard speed quotient value of 2.000, JND = 0.154 (SD = .043) for the glottal
      flow and JND = 0.319 (SD = .167) for the output pressure. For the speed quotient,
      there was no statistically significant difference between genders, but the
      difference between types of stimulus (glottal flow versus output pressure) was
      significant (p < .006). The variance among the JND values was significantly
      larger for the output pressure stimuli compared to the glottal flow stimuli for
      both the open quotient and the speed quotient.

PMID- 9619977
TI  - Approximations of open quotient and speed quotient from glottal airflow and EGG
      waveforms: effects of measurement criteria and sound pressure level.
AB  - Noninvasive measures of vocal fold activity are useful for describing normal and
      disordered voice production. Measures of open and speed quotient from glottal
      airflow and electroglottographic (EGG) waveforms have been used to describe
      timing events associated with vocal fold vibration. To date, there has been
      little consistency in the measurement criteria used to calculate quotient values.
      In this study, criteria of 20% and 50% were applied to the AC amplitude of
      glottal airflow and inverted EGG waveforms for measurement of open quotient.
      Criteria of 20%, 50%, and 80%, and a midslope criterion that segmented the
      waveform between 20% and 80% of the waveform amplitude, were used for the
      calculation of speed quotient. Subjects produced waveforms at sound pressure
      levels (SPL) of 70, 75, 80 and 85 dB. Results indicated that approximations of
      open quotient obtained from the glottal airflow waveform significantly decreased
      using both the 20% and 50% criteria as SPL increased from 80 to 85 dB. No
      significant changes were found in open quotient from the EGG waveform as a
      function of SPL. Results of speed quotient measures from the glottal airflow and
      EGG waveforms showed a generally increasing trend as SPL increased, although the
      differences were not statistically significant. The data suggest that the signal
      type, measurement criterion and SPL must be considered in interpreting quotient
      measures.

PMID- 9619978
TI  - Glottal configuration associated with fundamental frequency and vocal register.
AB  - Simultaneous measurements of mean airflow rate, vocal intensity and fundamental
      frequency were made during flexible video endoscopic recording of the vowel /i/
      sustained in two vocal registers, modal and falsetto. The glottal closure
      patterns of four males and four females were evaluated by visually inspecting the
      video images. Acoustic signals were recorded and analyzed to verify the frequency
      and intensity criteria. Aerodynamic analysis of mean airflow rate was done via
      Rothenberg mask and commercial software. Incomplete glottic closure was common in
      both males and females. The degree of closure was significantly higher for modal
      samples than for falsetto samples with frequency and intensity held constant. The
      shape of the glottal closure did not vary with changes in the mode of phonation.
      As expected, the mean airflow rate increased with decreased glottal closure. The
      results suggest that incomplete glottic closure should be considered as a normal
      glottal configuration in high frequency modal and falsetto phonation. Moreover,
      hourglass and spindle glottal configurations may also be found in both the modal
      and falsetto registers of normal subjects. These results also confirm the
      positive relationships between degree of glottal gap and mean airflow rate. Thus,
      mean airflow rate may be regarded as a criterion for judging degree of glottal
      closure.

PMID- 9619979
TI  - Endolaryngeal contact pressures.
AB  - In this work, we present a new method for in vivo endolaryngeal contact pressure
      measurement with a miniature pressure transducer. Using this methodology, contact
      pressures can be measured during videoendoscopy at different locations between
      the artyenoids and also at various locations along the membranous vocal folds.
      Twenty adults with organic and functional voice disorders and two vocally healthy
      adults participated as subjects. Endolaryngeal contact pressure measures were
      made during a series of phonatory tasks varying pitch, loudness, and phonatory
      onset and offset. Measures were also made during nonphonatory tasks, including
      throat clearing, coughing, Valsalva maneuvres, and gagging. The most remarkable
      findings were: (1) interarytenoid contact pressures were considerably greater
      than intraglottal contact pressures; (2) interarytenoid contact pressures were
      greater for lower than higher pitches; (3) both interarytenoid and intraglottal
      contact pressures were remarkably large during hard glottal attack; and (4)
      overall, the largest endolaryngeal pressures were recorded between the
      arytenoids, during a thoracic fixation maneuver and during gag reflex.

PMID- 9619980
TI  - Effects of laryngeal endoscopy on the vocal performance of young adult females
      with normal voices.
AB  - This study investigated changes in maximum phonation time and acoustic and
      perceptual measures of voice following topical anesthesia and laryngeal endoscopy
      with the flexible endoscope. Forty-four females, aged 18-33 years and with normal
      voices, performed four vocal tasks: (a) 3-second /i/ prolongation, (b) maximum
      phonation time on /i/, (c) stepwise scale-singing, and (d) reading a standard
      passage. Subjects performed these tasks prior to anesthesia, after anesthesia,
      and again during laryngeal endoscopy. Voice samples were analyzed forjitter,
      shimmer, harmonic-to-noise ratio, speaking fundamental frequency, maximum
      phonational frequency range, maximum phonation time, harshness, and breathiness.
      Results demonstrated significant reductions in maximum phonational frequency
      range following anesthesia and, during laryngeal endoscopy, reductions in maximum
      phonation time and increases in speaking fundamental frequency, minimum
      fundamental frequency on scale-singing, and breathiness. Clinicians using
      laryngeal endoscopy for evaluation and management of vocal dysfunction should,
      therefore, consider the possible effects of these procedures on vocal
      functioning.

PMID- 9619981
TI  - Quantitative color analysis of laryngeal erythema in chronic posterior
      laryngitis.
AB  - The purpose of this study was to quantitatively analyze the degree of erythema
      visible in the larynges of normal subjects and of patients with symptoms of
      chronic posterior laryngitis. Video-documented examinations of laryngoscopy were
      digitized and then analyzed using computer image analysis software that allowed
      quantification of average color values, hue, saturation, and brightness from
      digitized color images. Documented laryngoscopic images from 7 normal subjects
      and 64 patients complaining of chronic laryngitis symptoms were examined, and
      additional patient examinations which were obtained and documented during
      treatment for reflux laryngitis were analyzed. Analysis was made of five
      different areas of each laryngeal image: the right and left vocal folds, the
      right and left vocal processes, and the posterior arytenoid mucosa. Data analysis
      showed that average color value ratings of redness for the patients with chronic
      laryngitis were significantly (p <0.0561) greater than the average values for
      normal subjects for the vocal folds. Color values for redness of the posterior
      laryngeal structures and vocal folds in the patients who were treated for reflux
      laryngitis were significantly (p <0.05) reduced over time and correlated with the
      clinical response to treatment. The data suggest that computer color analysis of
      documented video-laryngoscopic examinations can provide quantitative data on
      degree of erythema and may be useful as a quantitative means of diagnosis and
      documentation of treatment outcome for reflux laryngitis.

PMID- 9619982
TI  - Voice disorders in patients with suspected laryngo-pharyngeal reflux disease.
AB  - Many symptoms have been recognized in association with laryngo-pharyngeal reflux
      disease (LPRD), but reports of perceptual voice disorders in this condition have
      been lacking to date. Forty-nine patients with suspected LPRD were studied for
      five specific perceptual voice characteristics, and these characteristics were
      compared to the same characteristics in individuals who had never seen an
      Otolaryngologist for a voice disorder or throat problem (controls). Sixteen of
      the suspected LPRD patients also underwent 24-hour pH probe studies. All patients
      with suspected LPRD had significantly increased abnormal perceptual voice
      characteristics (musculoskeletal tension, hard glottal attack, glottal fry,
      restricted tone placement, and hoarseness) compared to the controls. Statistical
      objective differences between the two groups was demonstrated by the presence of
      increased shimmer in patients with suspected LPRD compared to controls. The
      differential diagnosis between functional voice disorders and LPRD may be
      complex, and perceptual parameters may overlap. Interdisciplinary evaluation is
      advocated.

PMID- 9619983
TI  - Reflux and vocal disorders in singers with bulimia.
AB  - Dysphonia associated with bulimia has been described in the literature associated
      with vocal fold edema and polypoid changes. Laryngopharyngeat reflux (LPR) has
      been documented to cause reflux vocal fold pathology including edema and polypoid
      changes. We studied eight singers with bulimia and documented vocal fold
      pathology, including edema, posterior commissure hypertrophy, ventricular
      obliteration, and telangiectasia. Reflux was demonstrated in all eight. The
      results of this study showed that LPR may be a contributing factor to vocal
      disorders in singers with bulimia.

PMID- 9619984
TI  - Candida laryngitis appearing as leukoplakia and GERD.
AB  - The symptoms and physical findings of reflux laryngopharyngitis are
      characteristic, but the mucosal alterations evident in the larynx are not
      exclusive to reflux. When conventional reflux management produces an equivocal
      response, other etiologic factors such as mycotic laryngitis, need consideration.
      The differential diagnosis of dysphonia in an immunocompromised patient always
      includes mycotic infections, but mycotic laryngitis can also occur in the
      immunocompetent host. Laryngeal candidiasis can produce physical findings, such
      as erythema and leukoplakia, that are similar to reflux laryngopharyngitis.
      Predisposing factors include previous radiation therapy, antibiotic therapy,
      corticosteroids, and any alteration in the mucosal barrier. Diagnosis is
      established by mucosal biopsy with special staining of the tissue to identify the
      characteristic hyphae. Treatment of mycoses can be difficult and long-term
      therapy is often required.

PMID- 9619985
TI  - Etiology and treatment of psychogenic voice disorder: results of a follow-up
      study of thirty patients.
AB  - It is generally accepted that psychogenic voice disorder (PVD) is a result of
      psychosocial stress; however, systematic studies of etiological factors in this
      condition are few. Furthermore, although immediate effects of therapy are
      estimated to be good, relapses are frequent, and the long-term effects of therapy
      are not known. The present prospective and longitudinal study on 30 patients was
      thus focused on possible etiological factors, the course of therapy, and the long
      term results of therapy for PVD. The results indicate that interpersonal
      conflicts related to family and work are of basic importance in precipitating
      this condition. PVD is interpreted as a specific disorder of verbal emotional
      expression. Our therapy model in which vocal exercises are performed, together
      with training of communicative skills, seems rewarding. Relapses were not
      reported in 88% of the patients during the followup period of 1.9-8.4 years after
      therapy.

PMID- 9619986
TI  - The type I thyroplasty window: implications of normal thyroid cartilage
      thickness.
AB  - This paper describes the dimensions and placement of a standardized Isshiki Type
      I thyroplasty window and the thickness of the thyroid cartilage at the window
      corners. In addition, the intraoperative optimal medialization of a series of
      windows is compared to these cartilage thickness measurements and these
      comparisons analyzed for their implications in surgical approach. Fifty-one Type
      I thyroplasty windows were fashioned on 42 larynges (cadaveric and surgical).
      Measurements were taken of the window sizes, depth of medialization (surgical
      cases), and thickness of the thyroid cartilage at the four corners of the
      rectangular window. Sexes were kept separate because of inherent size differences
      of male and female larynges. From these physical measurements it is found that:
      (1) the thyroid cartilage window is not uniform in thickness throughout; there is
      a gradation of thickness from anterior to posterior and from superior to
      inferior; (2) when comparing the average depth of medialization to the window
      cartilage thickness in a standardized Isshiki window, the average distance of
      window depression almost equals the thyroid cartilage thickness, whereas
      posteriorly there is slightly more distance between the external surface of the
      window cartilage and the internal surface of the surrounding thyroid cartilage.
      Implications of the varying thickness of the thyroid cartilage and its
      relationship to the average depth of medialization in a standardized Isshiki
      thyroplasty window are discussed.

PMID- 9619987
TI  - Cricothyroid joint injury.
AB  - Cricothyroid joint injuries may result in severe voice dysfunction and may be
      associated with laryngeal pain. Otolaryngologists and radiologists should be
      familiar with this rarely recognized injury.

PMID- 9619988
TI  - Infrapetiole exploration of the supraglottis for exposure of the anterior glottal
      commissure.
AB  - Effective microlaryngoscopic surgery of the anterior glottal commissure depends
      on adequate exposure of this region. Despite the use of elevated vector
      suspension and external laryngeal counter-pressure, there are some individuals in
      whom inadequate exposure precludes execution of the planned surgery. To solve
      this problem, a procedure was designed in which the anterior vestibular folds and
      the infrapetiole region of the supraglottis are resected to facilitate complete
      exposure of the Broyle's ligament. The microspot carbon-dioxide laser is used
      with cold instruments to resect the anterior vestibular folds and thyroepiglottic
      ligament in continuity. After this tissue is removed, external counter-pressure
      then provides clear visualization of the anterior-superior thyroid lamina as well
      as the superior surface of the anterior commissure of the glottis. This procedure
      was used in ten cases in which the pathology included carcinoma, keratosis with
      atypia, and papillomatosis. This approach allows for a clear determination about
      whether early glottic cancer has invaded the thyroid lamina (T1 versus T4)
      without altering the structural integrity of Broyle's ligament, which avoids
      significant impairment of the voice. The exposure also allowed for en-block
      endoscopic resection of two anterior commissure carcinomas. Endoscopic resection
      of the infrapetiole region and anterior vestibular folds provides a gateway to
      the superior surface of the anterior glottal commissure. Furthermore, the
      procedure establishes an effective means to assess the depth of invasion of
      epithelial neoplasia to the underlying cartilage framework, as well as to
      facilitate en-block resection of carcinoma if it is appropriate.

PMID- 9619989
TI  - Intrahippocampal infusion of the NMDA receptor antagonist AP5 impairs retention
      of an inhibitory avoidance task: protection from impairment by pretraining or
      preexposure to the task apparatus.
AB  - The purpose of the present research was to further evaluate the role of
      hippocampal N-methyl-D-aspartate (NMDA) receptors in inhibitory avoidance task
      consolidation. Adult male Wistar rats were trained and tested in a step-down
      inhibitory avoidance task (0.4 mA footshock, 24 h training-test interval).
      Immediately after training, animals received a 0.5-microl intrahippocampal
      infusion of the NMDA receptor antagonist aminophosphonopentanoic acid (AP5) (5.0
      microg) or vehicle (phosphate buffer in saline, pH 7.4). The infusion of AP5
      impaired retention test performance. Both pretraining with a low footshock
      intensity (0.2 mA) or preexposure to the inhibitory avoidance box 24 h before
      training prevented the amnestic effect of AP5. The results suggest that
      hippocampal NMDA receptors are critical for neither the enhancement of retention
      induced by an additional training session nor the inhibitory avoidance retention
      in animals that have previously learned about the task environment by preexposure
      to the apparatus.

PMID- 9619990
TI  - Dose-dependent impairing effects of morphine on avoidance acquisition and
      performance in male mice.
AB  - The effects of morphine (6.3, 12.6, and 25.2 mg/kg) on active avoidance behavior
      of BALB/C mice are explored in three acquisition sessions and in two subsequent
      performance sessions. Morphine-treated animals showed an increase in avoidance
      acquisition with respect to control group without differences in performance.
      However, a dramatical, concomitant rise in the locomotor activity of the animals
      (increase in the number of crossings during the intertrial intervals) prompted us
      to transform the data employing a formula with which a measure of actual learning
      was obtained. Applying this formula, we have observed that morphine
      administration impairs, dose-dependently, acquisition and performance of
      avoidance. Thus, the impairing effects of morphine on avoidance could be masked
      by their stimulant effects on locomotor activity.

PMID- 9619991
TI  - Septal lesions impair the acquisition of a cued place navigation task:
      attentional or memory deficit?
AB  - These experiments were designed to analyze how medial septal lesions reducing the
      cholinergic innervation in the hippocampus might affect place learning. Rats with
      quisqualic lesions of the medial septal area (MS) were trained in a water maze
      and on a homing table where the escape position was located at a spatially fixed
      position and further indicated by a salient cue suspended above it. The lesioned
      rats were significantly impaired in reaching the cued escape platform during
      training. In addition rats, did not show any discrimination of the training
      sector during a probe trial in which no platform or cue was present. This
      impairment remained significant during further training in the absence of the
      cue. When the cued escape platform was located at an unpredictable spatial
      location, the MS-lesioned rats showed no deficit and spent more time under the
      cue than control rats during the probe trial. On the homing board, with a salient
      object in close proximity to the escape hole, the MS rats showed no deficit in
      escape latencies, although a significant reduction in spatial memory was
      observed. However, this was overcome by additional training in the absence of the
      cue. Under these conditions, rats with septal lesions were prone to develop a
      pure guidance strategy, whereas normal rats combined a guidance strategy with a
      memory of the escape position relative to more distant landmarks. The presence of
      a salient cue appeared to decrease attention to environmental landmarks, thus
      reducing spatial memory. These data confirm the general hypothesis that MS
      lesions reduce the capacity to rely on a representation of the relation between
      several landmarks with different salience.

PMID- 9619992
TI  - Sensitization of the Tritonia escape swim.
AB  - When repeatedly elicited, the oscillatory escape swim of the marine mollusc
      Tritonia diomedea undergoes habituation of the number of cycles per swim.
      Previous work has shown that this habituation is accompanied by sensitization of
      another feature of the behavior: latency to swim onset. Here we focused on the
      behavioral features of sensitization itself. Test swims elicited 5 min after a
      strong sensitizing head stimulus differed in several ways from control swims:
      sensitized animals had shorter latencies for gill and rhinophore withdrawal, a
      shorter latency for swim onset, a lower threshold for swim initiation, and an
      increased number of cycles per swim. Sensitized animals did not, however, swim
      any faster (no change in cycle period). A separate experiment found that swim
      onset latency also sensitized when Tritonia came into contact with one of their
      natural predators, the seastar Pycnopodia helianthoides, demonstrating the
      ecological relevance of this form of nonassociative learning. These results
      define the set of behavioral changes to be explained by cellular studies of
      sensitization in Tritonia.

PMID- 9619993
TI  - Effects of a single administration of oxytocin or vasopressin and their
      interactions with two selective receptor antagonists on memory storage in mice.
AB  - The neuropeptides arginine vasopressin (AVP) and oxytocin (OT) have been thought
      to play a significant role in behavioral regulation in general and in learning
      and memory in particular. Experimental evidence suggests that AVP improves, and
      OT impairs, learning and memory. The present paper investigates the posttraining
      effects of OT and of an OT receptor antagonist, and their interaction, on memory
      storage in mice. Additional studies were conducted to determine the specificity
      of the interaction between OT and its receptors. Male Swiss mice were tested 48 h
      after training in a one-trial step-through inhibitory avoidance task. Immediate
      posttraining subcutaneous injection of OT (0.01, 0.03, 0.10, 0.30, and 1.00
      microg/kg) impaired retention performance. The dose-response curve showed a U
      shaped form, with a significant impairment seen at doses of 0.10 and 0.30
      microg/kg of OT. In contrast, the immediate posttraining administration of the
      putative oxytocin receptor antagonist d(CH2)5[Tyr(Me)2, Thr4, Thy-NH(9)2]OVT
      (AOT, 0.03, 0.10, 0.30, and 1.00 microg/kg) significantly enhanced retention
      performance. The dose-response curve was an inverted "U" in this range of doses.
      However, of the doses tested, only 0.30 microg/kg was effective. Neither OT nor
      AOT affected response latencies in mice not given the footshock on the training
      trial, indicating that the actions of both treatments on retention performance
      were not due to nonspecific proactive effects on response latencies. Neither the
      imparing effects of OT (0.10 microg/kg) nor the enhancing effects of AOT (0.30
      microg/kg) were seen when the training-treatment interval was 180 min, suggesting
      that both treatments influenced the storage of recently acquired information. The
      effects of OT (0.10 microg/kg) on retention were prevented by AOT (0.03
      microg/kg) administered immediately after training, but 10 min prior to oxytocin
      treatment. This dose of antagonist did not affect retention by itself, either
      under the standard experimental conditions or in mice trained with a lower level
      of footshock. On the contrary, OT (0.10 microg/kg) impaired retention in mice
      pretreated with the V1a vasopressin receptor antagonist d(CH2)5[Tyr(Me)2]AVP
      (0.01 microg/kg), which, however, was able to prevent the enhancement of
      retention induced by posttraining administration of AVP (0.03 microg/kg).
      Finally, the effects of AVP (0.03 microg/kg) on retention were not prevented by
      AOT (0.03 microg/kg). Considered together, these findings suggest that the
      impairment of retention of an inhibitory avoidance response in mice induced by
      posttraining oxytocin is probably due to an interaction of the neuropeptide with
      specific receptors.

PMID- 9619994
TI  - Lesions of the caudal area of rabbit medial prefrontal cortex impair trace
      eyeblink conditioning.
AB  - The dorsolateral prefrontal cortex of the primate is an area known to be
      important for memory. Since the discovery of a homologous area in subprimate
      mammals, the caudal medial prefrontal cortex, rabbits have become useful in the
      investigation of working memory. The subprimate prefrontal cortex is intimately
      interconnected with the hippocampus, which is also recognized for its role in
      learning and memory. In addition, the hippocampus and prefrontal cortex have been
      shown to be similarly involved in a variety of tasks. Therefore, we hypothesized
      that the caudal medial prefrontal cortex of the rabbit would be necessary for
      acquisition of the hippocampally dependent trace eyeblink conditioning task. A
      total of 16 young rabbits (Oryctolagus cuniculus) received bilateral aspiration
      lesions of the prefrontal cortex. Six of the lesioned subjects were unable to
      acquire the trace eyeblink conditioning task, but were unimpaired when tested
      subsequently in the hippocampally independent delay conditioning task. The
      lesions of these 6 subjects either were limited to or extended into the caudal
      medial prefrontal cortex. In the remaining 10 subjects, which were not impaired
      in trace conditioning, the lesions were limited to the rostral pole. Our results
      support our original hypothesis and provide further evidence of the involvement
      of the subprimate caudal medial prefrontal cortex in learning.

PMID- 9619995
TI  - Amygdala modulation of multiple memory systems: hippocampus and caudate-putamen.
AB  - A series of five experiments examined the differential mnemonic roles of the
      hippocampus and caudate-putamen and the modulatory influence of the amygdala on
      hippocampal and caudate-putamen memory processes. Findings indicate that (a)
      posttraining intrahippocampal injections of amphetamine selectively enhance
      memory in a hidden platform water maze task, (b) posttraining intracaudate
      injections of amphetamine selectively enhance memory in a visible platform water
      maze task, (c) posttraining intra-amygdala injections of amphetamine enhance
      memory in both water maze tasks, (d) preretention intrahippocampal lidocaine
      injections block expression of the memory enhancing effects of posttraining
      intrahippocampal amphetamine injections in the hidden platform task, (e)
      preretention intracaudate lidocaine injections block expression of the memory
      enhancing effects of posttraining intracaudate amphetamine injections in the
      visible platform task, (f) preretention intra-amygdala lidocaine injections do
      not block the memory enhancing effect of posttraining intra-amygdala amphetamine
      injections on either task, (g) in the hidden platform task, posttraining
      intrahippocampal, but not intracaudate, lidocaine injections block the memory
      enhancing effects of posttraining intra-amygdala amphetamine, (h) in the visible
      platform task, posttraining intracaudate, but not intrahippocampal, lidocaine
      injections block the memory enhancing effects of posttraining intra-amygdala
      amphetamine. The findings indicate a double dissociation between the roles of the
      hippocampus and caudate-putamen in memory and suggest that the amygdala exerts a
      modulatory influence on both the hippocampal and caudate-putamen memory systems.

PMID- 9619996
TI  - Shuttle-box avoidance learning in mice: improvement by combined glucose and
      tacrine.
AB  - Glucose and the acetylcholinesterase inhibitor tacrine were tested, alone and in
      combination, in mice of the CD-1 strain subjected to five daily shuttle-box
      training sessions. Pretraining intraperitoneal administration of glucose alone
      (50-400 mg/kg) had no significant effect, while tacrine alone (0.5-3 mg/kg)
      improved avoidance acquisition at the dose of 2 mg/kg only. Significant avoidance
      learning improvements were instead produced by 50 or 100 mg/kg glucose combined
      with 0.5 or 1 mg/kg tacrine. The effects on shuttle-box avoidance acquisition
      produced by glucose combined with a cholinomimetic agent support the hypothesis
      that cholinergic mechanisms may be involved in the action of glucose on learning
      and memory. However, the main finding of the present study is related to the
      enhancement by glucose of the learning improving action of a drug clinically used
      as cognitive enhancer.

PMID- 9619997
TI  - Brief paradoxical sleep deprivation impairs reference, but not working, memory in
      the radial arm maze task.
AB  - Selective deprivation of paradoxical sleep after learning results in memory
      deficits in a variety of tasks. The present experiment was designed to examine
      the effects of paradoxical sleep deprivation (PSD) upon spatial working and
      reference memory. Adult male Sprague-Dawley rats were trained for 10 days in an
      eight-arm radial maze. Food rewards were available in four of the arms, while the
      other four arms were never baited. After each daily training session, different
      groups of rats were given 4 h of PSD, beginning either immediately, 4 h, or 8 h
      after the training experience. An additional group received PSD during the period
      13-24 h following daily training. The group that received PSD for 4 h immediately
      following daily training showed significant impairment compared to the other
      groups, but the deficit was limited to the reference component of the task. This
      result suggests that PSD causes deficits only in long-term forms of spatial
      memory.

PMID- 9619998
TI  - The Chiari II malformation: a surgical series.
AB  - Thirty patients between the ages of 7 months and 24 years were treated surgically
      for symptomatic Chiari II malformation at the Arkansas Children's Hospital. All
      patients underwent at least bony decompression of the malformation. Assessments
      of the patients' conditions were made at 6 weeks and 1 year after surgery, and
      complications of surgery were noted. For a majority of the patients, the
      presenting symptoms were resolved following treatment (74% at 6 weeks and 80% at
      1 year). Partial resolution occurred in several of the patients (17% at 6 weeks
      and 14% at 1 year). A small number remained the same at 6 weeks (6%) and at 1
      year (3%), while 1 patient was worse after surgery. Ten of the patients with
      complete resolution in the short term required repeat surgery an average of 49
      months after their original operation, after which they again attained complete
      resolution of their symptoms. Scales for clinical, radiographic and operative
      grading of the patients' conditions as mild, moderate or severe were devised, and
      these were employed to characterize the condition of each patient. Patients in
      each grading category had good results, with rates of complete symptomatic
      resolution ranging from 67 to 100%. Severity in each category was found to be
      well correlated with eventual recurrence of symptoms and need for reoperation.

PMID- 9619999
TI  - Acute neurologic dysfunction associated with high-dose chemotherapy and
      autologous bone marrow rescue for primary malignant brain tumors.
AB  - Acute neurologic complications occurred 103 times in 50 (54%) of 92 patients
      (primarily children) treated with high-dose chemotherapy and autologous bone
      marrow rescue for primary central nervous tumors. Different types of neurologic
      compromise occurred during the chemotherapy infusion as compared to the first 100
      days after the chemotherapy and the greater-than-100-day time period. The causes
      of the neurologic compromise were also time sensitive. BACKGROUND: Results of
      treatment for children with primary brain tumors using high-dose chemotherapy
      with autologous marrow rescue (ABMR) have been encouraging. However, the
      neurotoxicity associated with this technique remains a major concern. We reviewed
      the records of 92 patients who underwent ABMR for malignant brain tumors between
      1986 and 1992 for the occurrence and timing of acute neurologic dysfunction
      (AND). METHODS: Individual investigators at the participating institutions
      retrospectively completed standardized forms on each patient. The manner in which
      the distribution of AND versus time of treatment emerged led to the establishment
      of distinct time periods for data analysis and discussion. The pre-ABMR period
      included those events that occurred during the chemotherapy infusion, the early
      posttreatment period included the first 100 days following bone marrow rescue,
      and the late posttreatment period was greater than 100 days following bone marrow
      rescue. RESULTS: Fifty patients (54%) had 103 episodes of AND. AND included
      encephalopathies with or without hallucinations or coma (32), seizures (23),
      headaches (9), ataxia-tremor-dysarthria syndrome (7), anorexia and nausea
      syndrome (7) and others (25). During the chemotherapy infusion, encephalopathies
      and seizures were most common. Hallucinations occurred primarily related to drug
      infusion, while encephalopathies without hallucinations were usually due to
      demonstrable dysmetabolic states. In the 100 days following ABMR, dysmetabolic
      states and iatrogenic factors caused 45% and progressive disease caused 33% of
      AND. Greater than 100 days from ABMR, progressive disease caused 55% of AND; 7
      patients were noted to develop chronic anorexia and nausea of unclear etiology.
      The occurrence of neurologic compromise was not related to the chemotherapy
      regimens, tumor histology, tumor location, patient age, prior treatment, or the
      amount of tumor at time of treatment. Dexamethasone use was the only clinical
      factor associated with AND (p < 0.004). CONCLUSIONS: The cause of AND was
      definable for 95% of instances that occurred within 100 days of ABMR. Early AND
      was often iatrogenic and reversible. The greater the time from ABMR the more
      likely AND was due to progressive disease. Clinical factors could not predict the
      occurrence of AND as only the concurrent use of dexamethasone at the time of
      treatment proved significant. Although frequent, AND should not be considered a
      limiting toxicity of this approach or preclude the use of this technique.

PMID- 9620000
TI  - Pediatric hemifacial spasm: the efficacy of microvascular decompression.
AB  - Hemifacial spasm (HFS), generally a disease of the elderly, is caused by vascular
      compression of the seventh nerve. Vascular compression is thought to result from
      atherosclerotic changes within the vessels of the posterior fossa, and therefore
      rarely presents in childhood. Here we describe our experience with 12 patients
      with onset of HFS during childhood (age 18 or less) and who had surgical
      exploration of the cerebellopontine angle. These patients represent less than
      1.2% of the patient population with HFS operated upon at this institution during
      the study period. Nine patients had follow-up data extending over 83 months. All
      12 patients were found to have microvascular compression of the seventh nerve at
      the time of surgery. The most common operative finding was compression of the
      seventh nerve by a vein, alone or in combination with a branch of the anterior
      inferior cerebellar artery. At the time of discharge and after a mean follow-up
      period of 125 months, microvascular decompression resulted in complete relief of
      spasm in 67% of the patients.

PMID- 9620001
TI  - Midline dorsal appendages.
AB  - A case of a mature posterior cervical teratoma resembling two fingers and a case
      of a lumbosacral limb are presented. These are at least the seventh and eighth
      reported paraspinous or occipital teratomas with recognizable extremity
      development. Both anomalies had intradural extension and required exploration to
      decrease the likelihood of future spinal cord tethering. Preoperative evaluation,
      surgical technique, postoperative follow-up, and review of the literature are
      presented.

PMID- 9620002
TI  - Frontoethmoidal encephaloceles, a study of their pathogenesis.
AB  - A prospective clinical study of 30 patients with frontoethmoidal encephaloceles
      was performed in order to find support for a proposed theory concerning its
      pathogenesis, based on a previously performed embryological study and relevant
      findings in the literature. According to this proposed theory the pathogenesis of
      frontoethmoidal encephaloceles is primarily based on a disturbance in separation
      of neural and surface ectoderm at the site of final closure of the rostral
      neuropore during the final phase of neurulation in the 4th week of gestation. An
      insufficient occurrence of apoptosis might cause this disturbance in separation.
      The nonseparation of neural and surface ectoderm will result secondarily in a
      midline mesodermal defect. This mesodermal defect is reflected in the median
      skull defect at the site of the foramen caecum. The outgrowth of the nasal septum
      with the concomitant forward displacement of epidermis (surface ectoderm) and
      attached brain tissue (neural ectoderm) may act as herniating force. The patient
      study consisted of a clinical investigation, radiological investigations (X skull
      and CT scans), and surgical treatment in order to obtain specimens which were
      examined histologically. Clinical findings supportive of the proposed hypothesis
      are (1) the consistency in the location of the internal skull defect, (2) the
      close relationship between epidermal structures and glial tissue in 15 out of 29
      specimens, and (3) the presence of a normally developed nose in combination with
      interorbital hypertelorism in all patients. A discussion of these findings is
      presented with special reference to the embryological aspects.

PMID- 9620003
TI  - Normal diameter of filum terminale in children: in vivo measurement.
AB  - The hallmarks of tethered cord syndrome are a low-lying conus medullaris and a
      thick filum terminale. In diagnosing the tethered cord syndrome, the thick filum
      terminale is often defined as that greater than 2 mm in diameter. The cutoff of 2
      mm in diameter was derived from myelographic measurements a few decades ago, and
      the true normal diameter of the filum terminale diameter in children or adults
      remains unknown. We measured the diameters of the filum terminale in vivo in the
      operating room on 31 children (age range = 2-14 years; mean age = 5 years)
      undergoing selective dorsal rhizotomy for spastic cerebral palsy. None of them
      had clinical evidence of tethered cord syndrome. The conus medullaris and filum
      terminale were videotaped intraoperatively and images were transferred to an
      image analyzer; the filum diameters at 10 and 15 mm caudal to the conus
      medullaris were then measured extraoperatively using the computer graphics
      system. The diameter of the filum at 10 and 15 mm caudal to the conus was 1,211
      +/- 209 and 1,163 +/- 245 microm (mean +/- SD), respectively. In all children
      except one, the conus medullaris ended above the L2 level. The data indicate that
      filum terminales greater than 2 mm in diameter in children are abnormally thick.

PMID- 9620004
TI  - Corpus callosotomy for medically intractable seizures.
AB  - To identify factors influencing outcome and morbidity in patients selected for
      corpus callosotomy, we retrospectively reviewed 23 patients with intractable
      generalized seizures who underwent corpus callosotomy between 1991 and 1994.
      Three patients had a complete corpus callosotomy, while 20 had an anterior
      callosotomy. Three of those patients subsequently had completion of the anterior
      callosotomy. Overall, 41% of patients were nearly or completely free of the
      seizure types targeted for surgical treatment, while another 45% had seizures
      less than half as frequently. Four patients developed simple partial motor
      seizures after callosotomy. A transient disconnection syndrome was observed in
      57% of patients. The best predictor of good outcome was a normal preoperative
      MRI. Mentally retarded patients had poorer outcomes. Outcome was not predicted by
      extent of callosal section or lateralization on neurological examination, EEG,
      MRI, and SPECT. Completion of anterior callosotomy resulted in significant
      reductions in seizure frequency. Though most patients do not become seizure-free
      after corpus callosotomy, worthwhile palliation of an otherwise intractable
      illness can be achieved. An analysis of prognostic factors should lead to better
      selection of patients for surgery.

PMID- 9620005
TI  - Early hemispherectomy in a case of hemimegalencephaly.
AB  - We report a case with hemimegalencephaly and catastrophic epilepsy treated early
      at 4 months by functional hemispherectomy. The boy had intractable continuous
      epilepsy, with seizures every 10 min, hemiparesis and absence of psychomotor
      acquisition. Three years after hemispherectomy, the boy is seizure free and has a
      mild psychomotor delay. Hemiparesis and hemianopsia are unchanged. Early
      hemispherectomy, before 6 months of age, may control severe epilepsy and preserve
      the development of higher cortical functions in the nonhemimegalencephalic
      hemisphere.

PMID- 9620006
TI  - Coagulation of herniated cerebellar tonsils for cerebrospinal fluid pathway
      restoration.
AB  - In the past, many different surgical techniques have been proposed for treatment
      of the Chiari type I malformation. Despite the different technical
      considerations, in general, the treatment objectives have shared certain
      features: to prevent/ameliorate tonsillar crowding and to restore normal
      circulation of cerebrospinal fluid at the foramen magnum. We report a simple
      technique of coagulation of the herniated cerebellar tonsils in situ to
      decompress adjacent neural structures and to achieve the above-mentioned goals.
      When compared to the method of tonsillar resection, the procedure described
      herein affords the following two advantages: it is relatively less time-consuming
      and is more hemostatic. These two features minimize inflammation-mediated
      morbidity which may occur during the postoperative period.

PMID- 9620007
TI  - Images in Pediatric Neurosurgery. Intracranial dermal sinus and dermoid.

PMID- 9620008
TI  - The CSF accumulator: its role in the central nervous system and implications for
      advancing hydrocephalus shunt technology.

PMID- 9620009
TI  - Demyelinating disease of Schilder type in three young South African children:
      dramatic response to corticosteroids.
AB  - Three young children with the Schilder variant of multiple sclerosis were seen
      within a 3-year period at our hospital. The diagnosis was made on the basis of
      the typical (but not pathognomonic) clinical and magnetic resonance imaging (MRI)
      findings after eliminating other demyelinating and post-infectious disorders of
      the central nervous system. All three patients were treated with prednisone (2
      mg/kg/day), which resulted in complete recovery in one patient and mild and
      moderate residual hemiparesis in the two other patients, respectively.
      Corticosteroid therapy was continued until the patients' neurologic condition
      normalized or no further clinical improvement occurred. No relapses were seen
      after discontinuation of corticosteroid treatment. Computed tomographic (CT) scan
      and MRI findings after completion of corticosteroid therapy were equally dramatic
      and corresponded with the clinical improvement. A strongly positive tuberculin
      skin test and a positive history of contact with adult tuberculosis in two of our
      patients raise the possibility of a connection between tuberculosis and
      Schilder's disease.

PMID- 9620010
TI  - Clinical experience on headache in children: analysis of 92 cases.
AB  - We analyzed, retrospectively, 92 patients with headache to determine the changes
      in the order of frequency of causes with the development of neuroimaging studies
      and its efficacy in the investigation of patients with headache. The type of
      headache was redefined according to the International Headache Society (IHS)
      diagnostic criteria. Migraine was the most frequent cause of headache and the
      rest in decreasing order were: tension-type headache, sinusitis, and epilepsy.
      The percentage of the findings relevant to headache in computed tomographic (CT)
      scans, magnetic resonance images (MRIs), Waters' projection (radiographs), and
      electroencephalograms (EEGs) were respectively 4.2%, 33.3%, 16%, and 25%.
      Neuroimaging studies are not necessary in the routine evaluation of patients with
      headache unless there is an abnormality in the findings. When it is needed, MRI,
      which has higher yield, can take the place of CT scanning. The most important
      point is taking a proper history of headache and making a thorough physical and
      neurologic examination of the patient.

PMID- 9620011
TI  - Somatosensory evoked potentials with a unilateral migration disorder of the
      cerebrum.
AB  - The somatosensory evoked potentials in two children with a unilateral migration
      disorder (pachygyria) of the cerebrum, which was detected by MRI, were examined
      in order to evaluate the function of the malformed sensory cortex. A 5-year-old
      girl had slight left hemiparesis, seizures, and mental retardation, and a 4-month
      old boy had left hemiparesis. Neither patient showed distinct sensory
      disturbance. Short latency somatosensory evoked potentials and somatosensory
      evoked potentials recordings demonstrated that the early cortical component, N20,
      was absent and a positive wave appeared on paretic left-hand stimulation. On
      nonparetic right-hand stimulation, the primary evoked response (N20-P30) of the
      left hemisphere, which originates in Broadmann area 3b, was almost normal.
      Multichannel recordings on the scalp of one patient revealed that a positive wave
      without polarity inversion appeared posterior to the right central sulcus on
      median nerve stimulation on the paretic side. The radial dipole in the sensory
      cortex (area 1 or area 3a) or motor cortex (area 4) could have formed the
      positive/negative biphasic wave in the relatively wide centroparietal area in the
      present patients. In the case of unilateral cortical dysplasia, the malformed
      cortex with subnormal function of sensation might induce the change in the early
      component of somatosensory evoked potentials.

PMID- 9620012
TI  - "Extensor toe sign" by various methods in spastic children with cerebral palsy.
AB  - Upper motor neuron lesion in adults is usually associated with spasticity and
      "extensor toe sign" on plantar stimulation (extensor plantar response). There are
      various methods of eliciting this sign including the classic method by Babinski.
      Other methods produce this response when the area of reflexogenic zone is
      increased due to upper motor neuron lesion. There are varying reports of Babinski
      positivity in spastic cerebral palsy. This study was undertaken to assess the
      sensitivity of different methods of eliciting "extensor toe sign." An attempt has
      also been made to correlate the severity of spasticity with the combined
      "extensor toe sign" positivity by various methods and with the increase in
      reflexogenic zone. Eighty-one children with spastic cerebral palsy were examined.
      Twelve had hemiplegia; therefore, a total of 150 limbs were tested. "Extensor toe
      sign" was elicited by 12 different methods in each patient. The sensitivity of
      each method was calculated and compared with each other one. The assessment of
      spasticity was done using the Ashworth Tone Scale. The severity of spasticity was
      correlated with "extensor toe sign" positivity using various methods. Classic
      Babinski reflex was positive in 75% of cases, whereas Gonda-Allen sign was
      positive in 90% of cases followed by Allen-Cleckley (82%), Chaddock (74%), and
      Cornell (54%). All other signs had sensitivity of less than 30%. There was no
      increase in sensitivity after combining them. There was significant negative
      correlation between the spasticity and the combined "extensor toe sign"
      positivity (by all the methods). This study, therefore, suggests that the
      majority of patients with spastic cerebral palsy have positive "extensor toe
      sign." The Gonda-Allen method is more sensitive than the classic Babinski method.
      A positive "extensor toe sign" is negatively correlated to the degree of
      spasticity.

PMID- 9620013
TI  - Generalized tonic and tonic-clonic seizures of childhood.
AB  - In a retrospective analysis of all our patients with seizure onset prior to age
      16 years, 25 patients with primary generalized tonic (n = 10) or tonic-clonic (n
      = 15) seizures were identified. These patients constituted 5.7% of the total
      seizure patient population in our institute between the ages of 1 month and 16
      years. The natural history of generalized tonic-clonic seizures is known to be
      benign; however, that of isolated primary generalized tonic seizures is not
      clear. Therefore, an attempt was made to characterize the patients suffering from
      primary generalized tonic seizures and determine their outcome. Analysis of our
      patient population shows that both seizure types are characterized by early onset
      of generalized seizures that appear in normally developed children with a normal
      electroencephalographic background. The children usually respond quickly to
      antiepileptic drugs. A long-term follow-up (mean period of 7.6 years) was
      possible in 84% of the patients, and showed that 95% of them were seizure free at
      the end of the follow-up period. There was no significant difference between the
      two groups in regard to age of onset, family history, and seizures at follow-up.
      In conclusion, the natural history of patients with generalized tonic seizures is
      similar to the benign course of those with generalized tonic-clonic seizures.

PMID- 9620014
TI  - A description of the comprehensive test of nonverbal intelligence.
AB  - The Comprehensive Test of Nonverbal Intelligence, or CTONI, has become an
      essential compliment to the traditional tests of intelligence, such as the WISC
      III, DTLA-3, and the Binet. The CTONI provides examiners with a measure of
      nonverbal reasoning that requires no spoken language or complex motor skills. The
      CTONI has been proven to be unbiased with regard to gender, minority, or
      disabling condition. Finally, it is possible to estimate the intelligence of
      people without the contamination of social, ethnic, or disability bias.

PMID- 9620015
TI  - Neonatal encephalopathy in two boys in families with recurrent Rett syndrome.
AB  - Rett syndrome (RTT) has been described in its classic form only in females.
      Although the majority of cases are sporadic, familial cases give valuable insight
      into the genetic basis and phenotypic variability of the disorder. The exclusive
      occurrence of classic Rett syndrome in females led to the hypothesis that the
      Rett syndrome locus is likely to be X-linked and mutations are lethal in
      hemizygous males. We identified two boys in families with recurrent Rett syndrome
      who had encephalopathies with neonatal onset and who may represent the phenotype
      of males harboring Rett syndrome mutations. The difference in severity of disease
      in these males and their female relatives supports the location of Rett syndrome
      locus on the X-chromosome.

PMID- 9620016
TI  - Spinal cord mass and deferral of biopsy: a therapeutic dilemma.

PMID- 9620017
TI  - Inborn error of vitamin B12 metabolism: a treatable cause of childhood
      dementia/paralysis.

PMID- 9620018
TI  - Congenital insensitivity to pain with anhidrosis: lack of eccrine sweat gland
      innervation confirmed.

PMID- 9620019
TI  - Hyaluronidase treatment for intravenous phenytoin extravasation.

PMID- 9620020
TI  - Infection and America's blood supply: a 1998 status report.

PMID- 9620021
TI  - On trial: a malignant small cell tumor in a child: four wrongs do not make a
      right.

PMID- 9620022
TI  - Loss of tumor suppressor gene expression in high-grade but not low-grade non
      Hodgkin's lymphomas.
AB  - The products of the MTS1/CDKN2 and retinoblastoma (RB) tumor suppressor genes,
      p16 and pRB, act as agonists in controlling the late G1 cell cycle checkpoint.
      Inactivation of either gene occurs in a wide range of human malignant neoplasms.
      Data on the expression of both genes in the same set of malignant lymphoid
      neoplasms are scarce. We studied the p16/pRB pathway in low-grade and high-grade
      non-Hodgkin's lymphomas, using immunohistochemical techniques. Paraffin sections
      of 9 reactive lymph nodes and 43 low-grade and 60 high-grade malignant lymphomas
      were reacted with antibodies against pRB and p16. All benign lymph nodes showed a
      normal pattern of RB and MTS1/CDKN2 expression. Of 101 evaluable lymphomas, only
      a single high-grade tumor displayed loss of RB reactivity. Loss of p16 was
      identified in 14 of 55 evaluable high-grade lymphomas but not in any of the low
      grade lesions. All but 3 of the RB- and p16-negative cases were diffuse large
      cell lymphomas, for an abnormality rate of 55% in this category. While loss of RB
      function was a rare event in human lymphomagenesis, p16 was absent in some 25% of
      high-grade non-Hodgkin's lymphomas; diffuse large cell lymphomas were the primary
      target of tumor suppressor gene inactivation.

PMID- 9620023
TI  - Transient increase in blasts mimicking acute leukemia and progressing
      myelodysplasia in patients receiving growth factor.
AB  - Previous studies of the hematologic effects of granulocyte colony-stimulating
      factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have
      emphasized the morphologic changes induced by these growth factors, but few have
      reported increases in blasts. Here, we report six cases in which growth factor
      treatment resulted in a marked but temporary increase in peripheral and bone
      marrow blasts that led to diagnostic confusion with acute leukemia and high-grade
      myelodysplastic syndromes. Five of the six patients were receiving treatment for
      hematologic malignant neoplasms, and one patient had an optic nerve germinoma.
      Growth factor treatment included single agent therapy with G-CSF (three
      patients), GM-CSF (one patient), or simultaneous therapy with G-CSF and GM-CSF
      (two patients). In two patients, there was a dramatic increase in blasts in the
      peripheral blood (39% and 20%), whereas four had substantial increases in blasts
      on the aspirate smear (8%-41%). One patient had a medium-sized blast cluster
      shown on the core biopsy specimen. The blasts decreased after removal of growth
      factor in all patients. The findings indicate that growth factor therapy can
      cause a substantial transient increase in blasts in the bone marrow and
      peripheral blood that may be confused with relapse of acute leukemia or
      progression of a myelodysplastic syndrome.

PMID- 9620024
TI  - Improved detection of CD5 epitope in formalin-fixed paraffin-embedded sections of
      benign and neoplastic lymphoid tissues by using biotinylated tyramine enhancement
      after antigen retrieval.
AB  - To evaluate the effectiveness of the immunohistochemical staining of B- and T
      cell lymphomas with Leu-1 (clone L17F12 CD5 antibody, Becton Dickinson, San Jose,
      Calif) in formalin-fixed paraffin-embedded sections, we stained 12 specimens
      reflecting cases of chronic lymphocytic leukemia/small lymphocytic lymphoma, 7 of
      mantle cell lymphoma, 13 of T-cell lymphomas, and 9 of various B-cell neoplasms
      that do not ordinarily express CD5, using a streptavidin-horseradish peroxidase
      method with biotinylated tyramine enhancement after antigen retrieval. We were
      able to detect CD5 reactivity of neoplastic cells in 9 (75%) of 12 cases of
      chronic lymphocytic leukemia, 6 (86%) of 7 cases of mantle cell lymphoma, and 13
      (100%) of 13 of the T-cell lymphomas. B-cell neoplasms (9/9) not typically
      associated with CD5 expression showed no reactivity of tumor cells. We conclude
      that the Leu-1 (CD5) antibody, routinely used for cryopreserved tissues, is also
      effective in formalin-fixed paraffin-embedded sections using an antigen retrieval
      and streptavidin-horseradish peroxidase method with biotinylated tyramine.

PMID- 9620025
TI  - CD8-positive mantle cell lymphoma: a report of two cases.
AB  - Two cases of mantle cell lymphoma with a unique CD8+ phenotype are reported. Both
      patients had disease that was resistant to therapy; one patient had the blastic
      variant of mantle cell lymphoma. Flow cytometric analysis of bone marrow and
      cerebrospinal fluid samples revealed a phenotype consistent with mantle cell
      lymphoma, with the additional finding of CD8 positivity in 40% or more of the
      tumor cells in both cases. This is the first description of such a finding, and
      CD8+ mantle cell lymphoma may represent a unique type of B-cell neoplasia. Our
      findings may be important in the prediction of therapeutic response or in the
      detection of residual disease after therapy.

PMID- 9620026
TI  - Prostatic adenocarcinoma with atrophic features: a study of 202 consecutive
      completely embedded radical prostatectomy specimens.
AB  - Prostatic adenocarcinoma may manifest with morphologic features that may be
      mistaken for benign glandular atrophy. The incidence, morphometric extent, and
      diagnostic attributes of atrophic prostatic adenocarcinoma have not been defined
      in radical prostatectomy cases. The size, grade, and stage at which prostatic
      carcinomas manifest atrophic change and whether these atrophic appearing
      adenocarcinomatous glands are proliferative, quiescent, or dying (apoptotic) also
      have not been established. To characterize prostatic adenocarcinoma with atrophic
      features, we studied 202 consecutive completely embedded radical prostatectomy
      specimens from previously untreated patients. The histomorphologic attributes of
      atrophic carcinoma were compiled and compared with benign atrophy and usual
      prostatic adenocarcinoma without atrophic features. The atrophic carcinoma volume
      was quantitated by image analysis, the proliferation index was determined by Ki
      67 immunolabeling, and the apoptosis index was assessed by TdT [terminal
      deoxynucleotidyl transferase]-mediated dUTP [deoxyuridine triphosphate]-biotin
      nick end labeling (TUNEL). Of 202 prostatic adenocarcinoma cases, 32 (15.8%)
      demonstrated atrophic features. The malignant glands resembled benign atrophic
      glands by showing profound cytoplasmic volume loss, yet these glands almost
      always (96.4%) exhibited an infiltrative growth pattern, always lacked basal
      cells (confirmed by 34betaE12 immunostaining), and exhibited nuclear atypia with
      nucleomegaly and nucleolomegaly. The atrophic carcinoma foci had a mean volume of
      0.3 cc (range, 0.01-2 cc), representing a mean of 16% of total carcinoma volume.
      The mean proliferation index for atrophic prostatic carcinoma was 4% compared
      with 1.2% for benign atrophy and 5.3% for usual nonatrophic carcinoma. Apoptosis
      was identified in only 1 of 32 atrophic prostatic carcinomas. Carcinomas with and
      without atrophic features did not differ in histologic grade, tumor volume, or
      pathologic stage. Most atrophic carcinomas were moderately differentiated, of
      Gleason grade 3. We conclude that the atrophic pattern of prostatic carcinoma is
      a distinctive morphologic presentation of proliferating, intermediate-grade,
      prostatic adenocarcinoma that has significant diagnostic rather than prognostic
      implications.

PMID- 9620027
TI  - Detection of K-ras point mutations in the supernatants of peritoneal and pleural
      effusions for diagnosis complementary to cytologic examination.
AB  - To determine whether DNA analysis can be performed using the supernatants of body
      fluids after centrifugation at 2,000 rpm for 10 minutes, peritoneal or pleural
      effusions or bile were examined for K-ras mutations in 34 cases of pancreatic,
      colorectal, gastric, esophageal, or hepatocellular carcinoma and 15 noncancer
      cases. The polymerase chain reaction products for K-ras gene codons 2 to 97 of
      exons 1 and 2 were generated with 41 (93%) of 44 body cavity fluid and 5 (100%)
      of 5 bile samples. By the single strand conformation polymorphism method, point
      mutations were detected in the ascites supernatants of 8 (89%) of 9 cases of
      pancreatic carcinoma. In the remaining case, no point mutation was demonstrated
      because few malignant cells were present in the ascites fluid. Furthermore, K-ras
      point mutations were observed in the ascites supernatants of 2 cases of
      colorectal carcinoma and 1 case of gastric carcinoma. The DNA analysis of the
      supernatant of ascites fluid showed a K-ras point mutation in 3 cases of false
      negative cytologic diagnosis (2 cases of pancreatic carcinoma and 1 case of
      colorectal carcinoma). Direct sequencing confirmed identical point mutations in
      the supernatants, whole cell pellets, malignant cells from the cytologic smears
      of ascites fluid, and cancer tissues. This novel method allows simultaneous
      testing for genetic abnormalities in supernatants of body fluid, after removing
      cells for cytologic diagnosis.

PMID- 9620028
TI  - The role of conventional cytology, immunocytochemistry, and flow cytometric DNA
      ploidy in the evaluation of body cavity fluids: a prospective study of 52
      patients.
AB  - Fifty-two specimens of body cavity fluids from 52 patients were analyzed with
      conventional cytology, immunocytochemistry, and flow cytometric DNA ploidy
      methods to evaluate the most appropriate way of applying and interpreting
      immunocytochemistry and to evaluate the contribution of DNA ploidy analysis to
      conventional cytology in the diagnosis of body cavity fluids. The results suggest
      that conventional cytology still has an important role in the diagnosis of body
      cavity fluids. MOC 31 is the most sensitive monoclonal antibody for
      distinguishing benign mesothelial cells from malignant epithelial cells.
      Immunocytochemistry with the combination of cytokeratin, desmin, and MOC 31 with
      or without epithelial membrane antigen is suggested as a helpful ancillary method
      for the differential diagnosis of body cavity fluids. Flow cytometric DNA ploidy
      analysis also provides additional information in some difficult cases.
      Appropriate integration of clinical information and results of conventional
      cytology, immunocytochemistry, and flow cytometry are necessary to achieve the
      most accurate diagnosis in patients with effusion involving a body cavity.

PMID- 9620029
TI  - CD5 labeling of thymic carcinomas and other nonlymphoid neoplasms.
AB  - We studied 109 thymic tumors and 423 other neoplasms for immunocytochemical
      expression of CD5 in paraffin-embedded tissue using 2 monoclonal antibodies. One
      of the antibodies (clone CD5/54/B4) labeled 7 (29%) of 24 thymic carcinomas but
      did not stain any of the other neoplasms. In contrast, the other antibody (clone
      4C7) labeled 15 (62%) of 24 thymic carcinomas, 2 (2%) of 84 thymomas, 3 (8%) of
      37 lymphomas, and 14 (4%) of 386 other tumors. Among the lymphomas, 4C7 labeled 2
      of 4 peripheral T-cell lymphomas and 1 of 4 anaplastic large cell lymphomas.
      Clone 4C7 produced strong labeling of reactive T lymphocytes, whereas CD5/54/B4
      staining of these cells was weak or absent. No other normal cells seemed to stain
      with either antibody. In conclusion, one CD5 antibody clone (CD5/54/B4)
      specifically identified 30% of thymic carcinomas. The other CD5 antibody (clone
      4C7) identified 62% of thymic carcinomas but also labeled occasional other
      neoplasms.

PMID- 9620030
TI  - The status and distance of cone biopsy margins as a predictor of excision
      adequacy for endocervical adenocarcinoma in situ.
AB  - Cervical cone biopsy has become an important surgical procedure for endocervical
      adenocarcinoma in situ (AIS), especially for patients who desire to retain their
      fertility. Establishing the usefulness of the endocervical margin status in cone
      biopsy specimens as a predictor of residual AIS is paramount. We examined the
      status of the endocervical margin in the cone biopsy specimen, the distance
      between the most proximal AIS and the endocervical margin in the cone biopsy
      specimen, and the endocervical curettage (ECC) specimen performed at the time of
      cone biopsy and residual AIS in the hysterectomy specimens of 61 patients with
      specimens accessioned from 1968 through 1997; 43 (30%) of patients with a
      negative endocervical margin had residual AIS in the hysterectomy specimen.
      Conversely, 10 of 18 (56%) patients with a positive endocervical margin in the
      cone biopsy specimen had no AIS in the hysterectomy specimen. All 6 patients with
      AIS in the ECC specimen had residual AIS. No patient with an endocervical margin
      in the cone biopsy specimen greater than 10 mm had residual AIS. Patients with
      distances less than 10 mm had equal percentages of residual AIS. In general, more
      patients with a negative endocervical margin in the cone biopsy specimen had no
      residual AIS in the hysterectomy specimen than those with a positive endocervical
      margin in the cone biopsy specimen. However, the status of this margin is not
      useful for predicting the presence of residual AIS. Pathologists should report
      the distance between the endocervical cone biopsy margin and the closest AIS.

PMID- 9620031
TI  - Tumor angiogenesis in stage II colorectal carcinoma: association with survival.
AB  - We studied the frequency of microvessels in T3 N0 M0 colorectal carcinomas from
      patients with widely different survival times. Microvessels (<50 microm diameter)
      were enhanced by immunostaining with antibody to factor VIII-related antigen and
      counted in 40x high-power fields in sections of resected carcinomas from 9
      patients who died of disease in 24 months or less (short-term survivors) and 13
      who had no evidence of disease at 109 months or longer (long-term survivors). The
      means of the 10 highest counts for each case were compared between the long- and
      short-term survivor groups. The mean +/- SD microvessel count was 25.4 +/- 6.5
      for the short-term survivors and 30.3 +/- 6.4 for the long-term survivors. Median
      counts were 27.2 and 29.4, respectively. The distribution of microvessel counts
      was skewed toward higher counts in the long-term survivors. There was no
      correlation between microvessel counts and tumor site, size, or grade;
      lymphovascular invasion; or the presence of a mucinous component. Although there
      was a trend toward a higher frequency of microvessels in patients with longer
      survival, it is unlikely that microvessel count is an independent prognostic
      indicator for patients with T3 N0 M0 colorectal carcinoma because there is only a
      small difference in microvessel frequency between patients with widely different
      survival times.

PMID- 9620032
TI  - Adenocarcinoma in situ in cervical smears with a small cell (endometrioid)
      pattern: distinction from cells directly sampled from the upper endocervical
      canal or lower segment of the endometrium.
AB  - Adenocarcinoma in situ (AIS) with small, endometrioid cells in cervicovaginal
      smears, is a source of false-negative diagnoses because of the difficulty in
      distinguishing these cells from endometrial cells of the lower uterine segment or
      benign cells from the upper endocervical canal. This study was designed to
      elucidate the most useful criteria for this distinction. Three observers blinded
      to the actual diagnoses reviewed 29 preselected cases (AIS, 17; benign, 12) that
      had originally caused diagnostic difficulty. Each observer made a diagnosis and
      evaluated 15 preselected diagnostic criteria. All 3 observers agreed on the
      correct diagnosis in 19 (66%) of 29 cases, and at least 2 observers agreed on the
      correct diagnosis in 27 (93%) of 29 cases. No case was misdiagnosed by all 3
      observers. The most useful criteria for the diagnosis of AIS are a predominance
      of groups with marked crowding, focal feathering, nuclear hyperchromatism with
      coarsening of chromatin, and occasional mitotic figures. Sheets of cells,
      endometrial tubules, and endometrial stroma favor a benign diagnosis. Although 12
      (14%) of 87 possible diagnoses were erroneous, well-preserved, small,
      endometrioid AIS cells can be identified correctly on cervical smears and
      distinguished from epithelium from the lower uterine segment and high
      endocervical canal in most cases using the aforementioned criteria.

PMID- 9620033
TI  - Lack of efficacy for conventional gamma irradiation of platelet concentrates to
      abrogate bacterial growth.
AB  - The maximum storage time for platelet concentrates is 5 days, owing to the higher
      risk bacterial contamination with longer storage. The expiration date could
      potentially be extended if a rapid system to detect microbial contamination or a
      safe sterilization technique could be developed and easily implemented. Gamma
      irradiation has decreased bacterial contamination in food products. Conventional
      doses of gamma irradiation were tested for their efficacy in decreasing bacterial
      growth during the 5-day platelet shelf life. An initial pilot study determined
      that bacteria suspended in normal saline at concentrations of 1 to 2 x 10(7)
      colony-forming units per milliliter showed a dose-related susceptibility to gamma
      irradiation. Subsequently, four platelet concentrates were pooled, inoculated
      with a known concentration of Staphylococcus autreus or Serratia marcescens, and
      divided. The concentrates were exposed to varying amounts of gamma irradiation,
      ie, no irradiation (control), 25, 50, and 75 Gy, and subjected to typical blood
      bank storage conditions. The platelet concentrates were sampled daily for 7
      consecutive days to monitor bacterial growth by quantitative cultures. An inverse
      linear dose-related extinction of bacteria was evident in the pilot study with an
      extrapolated total kill in the 100 to 150 Gy range. There is no difference in
      bacterial growth with S aureus using irradiation levels from 0 to 75 Gy. A 1-day
      delay in bacterial growth at 75 Gy was found with S marcescens compared with
      units irradiated with 0 through 50 Gy. Exposure of bacteria-contaminated platelet
      concentrates on storage day zero to gamma irradiation at levels up to 75 Gy is
      ineffective at sterilizing the platelet concentrates. Higher levels of
      irradiation may be effective in sterilizing platelet concentrates. Function,
      survival, and sterility after higher than conventional levels of irradiation need
      further study.

PMID- 9620034
TI  - Evaluation of a new rapid D-dimer assay for clinically suspected deep venous
      thrombosis (Liatest D-dimer).
AB  - In previous studies, enzyme-linked immunosorbent assays (ELISA) for plasma D
      dimer analysis have demonstrated high sensitivity, suggesting their potential
      usefulness in excluding deep venous thrombosis (DVT). We evaluated the usefulness
      of a new D-dimer test (Liatest D-dimer) for suspected DVT in a prospective study
      of patients admitted to the hospital because of recent (not exceeding 1 week
      before admission) clinical signs. Contrast venography or compression
      ultrasonography or both were performed within 24 hours of admission. A new
      quantitative determination of D-dimer concentration using a suspension of
      microlatex particles coated with specific antibodies was tested. A standard
      plasma D-dimer ELISA measurement was also performed. Of 464 patients, 276 had a
      proven DVT (distal, 74; proximal, 202). For a cutoff level of 400 ng/mL,
      sensitivity of the Liatest method in the diagnosis of overall DVT was 94.6% (95%
      confidence interval, 92.0%-97.0%), and the specificity was 35% (95% confidence
      interval, 28%-42%). The sensitivity and negative predictive value were 98.5% and
      95.6%, respectively, in the diagnosis of proximal DVT, but only 83.8% and 84.6%,
      respectively, in the diagnosis of distal DVT. This new rapid Liatest D-dimer
      assay seems to be highly sensitive and could replace the ELISA method in
      excluding patients with proximal DVT. Both methods provide lower sensitivity for
      distal DVT.

PMID- 9620035
TI  - Prolonged prothrombin time and activated partial thromboplastin time due to
      underfilled specimen tubes with 109 mmol/L (3.2%) citrate anticoagulant.
AB  - Underfilling of specimen tubes containing 129 mmol/L (3.8%) buffered citrate
      prolongs prothrombin time (PT) and activated partial thromboplastin time (APTT)
      values. We studied this phenomenon by using 109 mmol/L (3.2%) buffered citrate as
      the anticoagulant, anticipating some increase in tolerance to underfilling.
      Venous blood drawn from 12 healthy subjects and 30 patients receiving long-term
      oral warfarin therapy was mixed with 109 mmol/L buffered citrate solution in
      proportions equivalent to filling the collection tubes from 52% to 100% of
      capacity. Accurate PT values were obtained from normal specimens if the tubes
      were filled to 65% or more of capacity. Accurate PT results in the therapeutic
      range were obtained only with filling to 80% or more of capacity (using a
      "moderately sensitive" thromboplastin reagent, International Sensitivity Index
      [ISI] = 2.06) or 90% or more of capacity (using a "highly sensitive"
      thromboplastin reagent, ISI = 1.01). In contrast, APTT was much less tolerant to
      underfilling, with prolonged values observed in most specimens filled to less
      than 90% of capacity. No false low values were observed. Specimen tubes should be
      filled to at least 90% of capacity to avoid falsely elevated PT or APTT results,
      but values within the reference range may be acceptable even from underfilled
      tubes.

PMID- 9620036
TI  - Stability of plasma for add-on PT and APTT tests.
AB  - We conducted studies to determine at what time point an add-on prothrombin time
      (PT) or activated partial thromboplastin time (APTT) test can be honored on
      specimens that have been received in the laboratory hours earlier without
      yielding results with clinically significant differences from those if the test
      had been performed on the original unstored plasma. PT and APTT tests were
      performed on blood samples from 20 healthy subjects, 30 patients receiving
      warfarin, and 30 patients receiving heparin anticoagulation therapy. The tests
      were performed on plasma prepared initially after the samples were obtained. The
      same tests were assayed on plasma that had been left on spun-down blood cells at
      room temperature for 2, 4, and 8 hours. We found that the PT of the majority of
      plasma samples from healthy subjects and from patients receiving oral
      anticoagulant therapy tended to become shorter on storage. However, the
      difference in PT values was small and had no clinical significance. In most
      cases, the APTT values for the stored plasma from healthy subjects tended to
      increase with time. Except in one specimen in which the 8-hour add-on APTT was
      1.2 seconds longer than the APTT result for the original sample, all others had
      APTT results less than 1.2 seconds longer than the original values. In patients
      receiving heparin, the differences in APTT values between the initial and add-on
      tests were larger than those observed for healthy subjects. However, those
      differences are not beyond what we would accept for duplicate checks for
      heparinized samples with high APTT values. Unlike samples from healthy subjects,
      there was no obvious trend of time-related prolongation of the APTT in
      heparinized plasma. These results led us to believe that within an 8-hour period
      and with plasma on spun-down cells at room temperature, add-on tests for PT and
      APTT could be performed with results similar to what would be obtained from
      testing unstored samples.

PMID- 9620037
TI  - Falsely elevated INR results due to the sensitivity of a thromboplastin reagent
      to heparin.
AB  - The aim of this study was to determine the effect of heparin therapy on the
      international normalized ratio (INR). In vitro heparin sensitivity curves were
      created using normal and warfarinized plasma samples from patients. The INR
      results were measured with each of two reagents. In addition, a comparison of INR
      values with these two reagents was performed on plasma from patients receiving
      therapeutic heparin and warfarin. The INR values were measured before and after
      heparin removal with a heparin adsorbent system. While one of the reagents was
      found to be sensitive to even low levels of therapeutic heparin, the other
      thromboplastin was resistant up to at least 0.9 U/mL. The INR values determined
      for patients with one of the reagents were found to be erroneously elevated by an
      average of 16%. The error ranged from 2% to 55% depending on the in vivo heparin
      concentration. With the other reagent, the INR values were not substantially
      affected by heparin. Previous studies have described the effect or lack thereof
      of heparin on the prothrombin time. The present study demonstrates that the
      degree to which INR results are prolonged by heparin therapy depends on the
      reagent formulation. As the therapeutic index for monitoring warfarin is
      relatively narrow (2.0-3.0), an INR value that is falsely elevated due to reagent
      sensitivity may precipitate premature cessation of heparin therapy and place
      certain patients at risk for recurrent thrombosis in the short term.

PMID- 9620038
TI  - Problems associated with passively transfused blood group alloantibodies.

PMID- 9620039
TI  - Seroprevalence of HHV-8 antibodies in HIV-positive homosexual men without
      Kaposi's sarcoma and their clinical follow-up.
AB  - Human herpesvirus 8 (HHV-8) has been associated with Kaposi's sarcoma (KS).
      Because KS is most frequently seen in HIV-positive homosexual men, we
      retrospectively evaluated the seroprevalence of HHV-8 in this risk group and
      compared the clinical history and clinical course of the HHV-8-negative and HHV-8
      positive groups. The study was performed by analyzing banked serum samples from
      asymptomatic HIV-positive men. HHV-8 seropositivity was determined by an indirect
      immunofluorescence test. A total of 56% of patients (42/75) were seropositive for
      anti-HHV-8 IgG antibodies as opposed to 12% of 40 age-matched HIV-negative
      controls. Median CD4 counts at study entry were significantly lower in the HHV-8
      positive group than in the HHV-8-negative group (520 vs 686); however, the
      percentage decrease during a 30-month follow-up did not differ significantly. KS
      developed in two patients during follow-up; both were HHV-8-positive and had CD4
      counts of less than 200/microL at the time of clinical manifestation. One HHV-8
      positive patient in whom AIDS developed died of infectious complications. The
      longest follow-up in the HHV-8-positive cohort without development of KS was 81
      months. We conclude that HHV-8 has a high seroprevalence in asymptomatic,
      homosexual, HIV-positive persons. An HHV-8 infection can precede the development
      of KS by many years. Immunosuppression below a certain threshold may trigger the
      clinical manifestation of KS.

PMID- 9620040
TI  - Automated screening.

PMID- 9620041
TI  - Automated screening.

PMID- 9620042
TI  - All-cause mortality and cardiovascular disease mortality in three American Indian
      populations, aged 45-74 years, 1984-1988. The Strong Heart Study.
AB  - Community mortality surveillance for 1984-1988 was conducted by researchers of
      the Strong Heart Study, which examined the incidence, prevalence, and risk
      factors of cardiovascular disease in three American Indian populations, aged 45
      74 years, in Arizona, Oklahoma, and South/North Dakota. All-cause and
      cardiovascular disease mortality rates were determined through the use of death
      certificate data. Cardiovascular disease deaths were confirmed by independent
      systematic review of medical records. In all three populations, men had higher
      all-cause and cardiovascular disease mortality rates than did women. Oklahoma
      exhibited slightly lower 5-year, age-adjusted, all-cause mortality (96/1,000)
      than did Arizona (107/1,000) and South/North Dakota (114/1,000). The leading
      cause of death among both sexes in Oklahoma and in South/North Dakota was
      cardiovascular disease. Diabetes mellitus led among Arizona women. The other
      major causes of death were cancer, liver disease including cirrhosis, and injury.
      When compared with the rates in each state, average annual all-cause mortality
      rates were higher for the American Indian populations in almost every age group.
      The all-cause annual mortality rates in the three Indian populations were close
      to rates in the US black population and higher than the rates of the entire US
      population and of US whites. This trend was amplified in the 45- to 64-year age
      group. Only in the 65- to 74-year age group did mortality rates in the Indian
      population approach those of the US population. Cardiovascular disease mortality
      rates were close to the US averages in Arizona and Oklahoma, but they were more
      than two times higher in South/North Dakota among those between 45 and 64 years
      of age. Thus, American Indians in Arizona, Oklahoma, and South/North Dakota
      exhibit high all-cause mortality rates. In particular, the South/North Dakota
      population cardiovascular disease death rate appears to present a potential
      target for community-based programs to intervene on known risk factors to promote
      healthy lifestyles.

PMID- 9620043
TI  - Invited commentary: Cardiovascular mortality in American Indians: paradox
      explained?

PMID- 9620044
TI  - Pulmonary function levels as predictors of mortality in a national sample of US
      adults.
AB  - Single breath pulmonary diffusing capacity for carbon monoxide (DL(CO)) was
      examined as a predictor of all-cause mortality among 4,333 subjects who were aged
      25-74 years at baseline in the First National Health and Nutrition Examination
      Survey (NHANES I) conducted from 1971 to 1975. The relation of the percentage of
      predicted DL(CO) to all-cause mortality was examined in a Cox proportional hazard
      model that included age, sex, race, current smoking status, systolic blood
      pressure, serum cholesterol, alcohol consumption, body mass index, percentage of
      predicted forced vital capacity (FVC), and the ratio of forced expiratory volume
      at 1 second (FEV1) to FVC. Mortality had a linear association with the percentage
      of predicted FVC (rate ratio (RR) = 1.12, 95% confidence interval (CI) 1.08-1.17,
      for a 10% decrement) and a significantly nonlinear association with the
      percentage of predicted DL(CO) with an adverse effect that was clearly evident
      for levels below 85% of those predicted (RR = 1.24, 95% CI 1.12-1.37 for a 10%
      decrement). The relative hazard for the percentage of predicted DL(CO) below 85%
      was not modified by sex, smoking status, or exclusion of subjects with clinical
      respiratory disease on the initial examination. This association with the
      percentage of predicted DL(CO) was present among 3,005 subjects with FEV1 levels
      above 90% of those predicted. Thus, pulmonary diffusing capacity below 85% of
      predicted levels is a significant predictor of the all-cause mortality rate
      within the general US population independent of standard spirometry measures and
      even in the absence of apparent clinical respiratory disease.

PMID- 9620045
TI  - Higher instrumental activities of daily living disability in Hispanics compared
      with non-Hispanic whites in rural Colorado. The San Luis Valley Health and Aging
      Study.
AB  - This study examined Hispanic versus non-Hispanic white patterns of needing
      assistance with instrumental activities of daily living (IADL). The authors
      interviewed 798 Hispanic and 614 non-Hispanic white residents of rural Colorado,
      who were aged 60 years and older between 1993 and 1995. Seventy-five participants
      were nursing home residents at the time of the interview. Community-dwelling
      Hispanics were 1.6 times as likely as non-Hispanic whites to need assistance with
      at least one IADL task (95% confidence interval 1.25-2.13). A larger proportion
      of disabled non-Hispanic whites were in nursing homes but, after including
      nursing home residents, Hispanics remained significantly more likely to need
      assistance on at least one IADL task (odds ratio = 1.49, 95% confidence interval
      1.16-1.93). Hispanics were also more likely to have difficulty on observed
      performance tasks. The Hispanic excess was not removed by adjusting for chronic
      disease, reported difficulty walking, or income. English language proficiency
      adjustment lowered the Hispanic excess, but adjusting for years of education or
      Mini-Mental State Examination scores more completely removed the ethnic
      differences. Higher education was protective for both Hispanic and non-Hispanic
      white elderly. Efforts to further investigate what facets or correlates of
      education are operating may offer useful insights into limiting IADL difficulties
      in future cohorts.

PMID- 9620046
TI  - Risk factors for lung cancer in young adults.
AB  - Risk factors for early onset of lung cancer are relatively unknown. In a case
      control study, carried out in Germany between 1990 and 1996, the effects of
      smoking and familial aggregation of cancer were compared in 251 young cases and
      280 young controls (< or = 45 years) and in 2,009 older cases and 2,039 older
      controls (55-69 years). The male/female ratio was 2.6/1 in young patients and
      5.6/1 in older patients. Adenocarcinomas were more frequent in young men than in
      older men (41 % vs. 28%). Duration of smoking and amount smoked showed
      significantly increased odds ratios for lung cancer in both age groups. Lung
      cancer in a first degree relative was associated with a 2.6-fold (95% confidence
      interval (CI) 1.1-6.0) increase in the risk of lung cancer in the young age
      group, but no elevated risk was seen in the older group (OR = 1.2, 95% CI 0.9
      1.6). Smoking-related cancer in relatives with the age at diagnosis under 46
      years was associated with an increased risk of lung cancer in the young group (OR
      = 5.6, 95% CI 0.7-46.9) but not in the older group (OR = 0.7, 95% CI 0.3-1.5).
      Results indicated that lung cancer risk in young and older age groups shows
      remarkable differences with respect to sex, histologic type, and genetic
      predisposition.

PMID- 9620047
TI  - Cancer incidence in a cohort of infertile women.
AB  - Among 2,496 infertile Israeli women treated between 1964 and 1974, 143 cancer
      cases were observed as compared with 116.1 expected (standardized incidence ratio
      (SIR) = 1.2, 95% confidence interval (CI) 1.0-1.5) through 1991. Site-specific
      analysis revealed 12 ovarian cancers versus 7.2 expected (SIR = 1.6, 95% CI 0.8
      2.9), 21 endometrial cancers versus 4.3 expected (SIR = 4.85, 95% CI 3.0-7.4),
      and 59 breast cancers versus 46.6 expected (SIR = 1.3, 95% CI 0.96-1.6).
      Sensitivity analysis revealed that confounding was unlikely to explain the raised
      risk of endometrial cancer, but nulliparity might explain the increased risk of
      ovarian cancer. The excess of endometrial cancer was prominent among patients
      with normal estrogen production but progesterone deficiency (SIR = 9.4, 95% CI
      5.0-16.0). The risk for ovarian cancer was similar among the total groups of
      treated and untreated patients (SIR = 1.7 vs. 1.6). The standardized incidence
      ratio for endometrial cancer was higher among the treated group than the
      untreated group, although not significantly. Treatment with ovulation-inducing
      drugs does not appear to increase the risk for ovarian cancer, but its role
      cannot be completely excluded.

PMID- 9620048
TI  - Meta-analysis of coffee consumption and risk of colorectal cancer.
AB  - Several studies have found that coffee consumption is related to a lower risk of
      colorectal cancer, but results have not been consistent. Thus, a meta-analysis of
      the published articles was conducted to examine this relation. Because of the
      various ways data were collected and analyzed, a "semiquantitative" approach that
      compared the high versus the low category of intake for each study was used. The
      combined results from 12 case-control studies showed an inverse association
      between coffee consumption and risk of colorectal cancer (pooled relative risk
      (estimated by odds ratio) for high vs. low category of coffee consumption (RR) =
      0.72, 95% confidence interval (CI) 0.61-0.84); the findings were similar in
      population-based and hospital-based case-control studies. Five cohort studies did
      not support an association (pooled RR = 0.97, 95% CI 0.73-1.29). The combined
      results of all studies were driven largely by the case-control studies, which
      comprised 85 percent of the cases (RR = 0.76, 95% CI 0.66-0.89). The lower risk
      of colorectal cancer among substantial coffee drinkers was observed in studies
      from Asia, Northern and Southern Europe, and North America. The results of this
      meta-analysis indicate a lower risk of colorectal cancer associated with
      substantial consumption of coffee, but they are inconclusive because of
      inconsistencies between case-control and prospective studies, the lack of control
      for important covariates in many of the studies, and the possibility that
      individuals at high risk of colorectal cancer avoid coffee consumption. Several
      ongoing prospective cohort studies, based on extensive dietary questionnaires,
      may provide important new data to evaluate this hypothesis.

PMID- 9620049
TI  - Influence of diabetes during pregnancy on gestational age-specific newborn weight
      among US black and US white infants.
AB  - This study examined the impact of maternal diabetes on birth weight for
      gestational age patterns of all term black infants and white infants in the
      United States using data derived from the 1990-1991 US Live Birth File of the
      National Center for Health Statistics. Infants of both black mothers and white
      mothers exhibited the expected fetal overgrowth associated with maternal
      diabetes. However, the increase in birth weight was much greater in infants of
      black than white diabetic mothers in comparison with their nondiabetic
      counterparts, as measured by the discrepancy in birth weight between infants of
      diabetic and nondiabetic mothers at each gestational week, the incidence of large
      for gestational age, high birth weight, small for gestational age, and low birth
      weight. After adjustment for maternal hypertension, prenatal care use, and
      sociodemographic factors, the disparity in mean birth weight associated with
      diabetes was 211.67 g in black infants and 115.74 g in white infants. The
      adjusted odds ratios of birth weight > or = 4,000 g were 2.98 (95% confidence
      interval 2.89-3.12) for black infants and 1.83 (95% confidence interval 1.78
      1.89) for white infants. Given the potential risks for mothers and infants
      consequent to maternal diabetes and fetal hyperinsulinemia, further investigation
      of the prevalence, characteristics, and outcomes of diabetes during pregnancy
      among black mothers and infants is warranted.

PMID- 9620050
TI  - Comparison of risk factors for preeclampsia and gestational hypertension in a
      population-based cohort study.
AB  - The objective of this study was to evaluate and compare risk factor patterns in
      association with preeclampsia and gestational hypertension. The data were
      collected from The Swedish Medical Birth Register and include all nulliparas aged
      34 years or less who gave birth at the University Hospital of Uppsala, Sweden,
      during 1987-1993. Of these 10,666 women, 4.4% developed gestational hypertension,
      and 5.2% developed preeclampsia. The following risk factors were significantly
      associated with increased risk of preeclampsia: type 1 diabetes (odds ratio =
      5.58, 95% confidence interval 2.72-11.43), gestational diabetes (odds ratio =
      3.11, 95% confidence interval 1.61-6.00), and twin birth (odds ratio = 4.17, 95%
      confidence interval 2.30-7.55). The positive associations between these variables
      and the risk of gestational hypertension were weaker and nonsignificant. Compared
      with underweight women (body mass index < 19.8), obese women (body mass index >
      29) had increased risks of both gestational hypertension (odds ratio = 4.85, 95%
      confidence interval 1.97-11.92) and preeclampsia (odds ratio = 5.19, 95%
      confidence interval 2.35-11.48). Significantly lower risks of preeclampsia and
      gestational hypertension were observed for women born outside Nordic countries
      and in association with maternal smoking and summer birth. The similarities in
      risk factor patterns may indicate similarities in the biologic mechanisms
      underlying the two conditions.

PMID- 9620051
TI  - Use of urine biomarkers to evaluate menstrual function in healthy premenopausal
      women.
AB  - A total of 403 healthy, premenopausal women, residing near Santa Clara,
      California, were recruited from a large health care plan in California for a
      study of menstrual function. After a telephone interview, participants collected
      daily urine samples and recorded bleeding and other information in diaries. Data
      were collected during 1990-1991. Urine samples were analyzed for creatinine and
      for estradiol and progesterone metabolites by enzyme-linked immunoassay. Computer
      algorithms were developed to derive menstrual segment length, ovulatory status,
      day of ovulation, and other parameters from the urine and diary data. (We use
      "segment" rather than "cycle" to avoid implying that normal cycling occurred.)
      The average length of participation was 141 (standard deviation, 45) days. The
      mean segment length was 28.8 (standard deviation, 4.4) days; follicular phase
      length, 16.0 (standard deviation, 4.4) days; and luteal phase length, 12.9
      (standard deviation, 1.7) days; 19 (4.7%) women experienced anovulatory episodes.
      In exploratory multivariate analyses, important associations included the
      following: age of > or = 35 years with decreased segment and follicular phase
      lengths; heavier weight (upper quartile) with anovulation and increased
      follicular phase and decreased luteal phase lengths; Hispanic ethnicity with
      anovulation and increased segment length; and past difficulty in achieving
      pregnancy with anovulation and increased length and variability of segments and
      follicular phases. Urine biomarkers can be used successfully to evaluate
      menstrual function in epidemiologic studies.

PMID- 9620052
TI  - Determinants of obesity-related underreporting of energy intake.
AB  - Data from an ongoing Dutch health examination monitoring project carried out in
      1995 (n = 2,079 men and 2,467 women, aged 20-65 years) were used to study whether
      various determinants of underreporting of energy intake influenced the
      association between underreporting and body mass index. Further, the authors
      examined whether these determinants were mutually independent predictors of
      underreporting. As a measure for the degree of underreporting, they calculated
      energy ratios of reported daily energy intake divided by the estimated basal
      metabolic rate. They observed that underreporting occurred more with increasing
      degrees of overweight in men and women. Each increase in body mass index by 1
      kg/m2 was associated with a decrease in reported energy intake/basal metabolic
      rate (in men, beta = -0.0364; standard error, 0.0024; in women, beta = -0.0262;
      standard error, 0.0018). After adjustment for age, education, smoking habits,
      physical activity, dieting behavior, and dieting frequency during the last year,
      the slopes were reduced by 29% in men and 17% in women but remained negative and
      highly statistically significant. Adjustment for current dieting behavior
      particularly decreased the association between body mass index and
      underreporting. Age was another independent determinant of underreporting in men
      and women and, in men only, so were smoking habits and education level. In
      conclusion, overweight individuals give biased dietary information, and this may
      distort the relations between self-reported dietary intake and diseases related
      to body mass index.

PMID- 9620053
TI  - Measuring the burden of common morbidities: sampling disease experience versus
      continuous surveillance.
AB  - Longitudinal prevalence, the proportion of all days of observation that a given
      individual manifests symptoms of illness, is a measure of disease frequency that
      is easy to generate from daily morbidity data and has been shown to be strongly
      related to subsequent health outcome. It is hypothesized that this measure could
      be derived using a representative sample of days of observation rather than
      continuous surveillance. The authors use 1990-1991 data from a Brazilian
      supplementation trial comprising a year's daily records of the occurrence of
      diarrhea, fever, and cough in 906 children under 5 years of age to examine how
      many days of morbidity data need to be observed to rank subjects into quintiles
      of illness frequency. Systematic samples of the full data set, based on every
      2nd, 3rd, 5th, 10th, 15th, 20th, and 30th day of data, are compared with the
      continuous record. For diarrhea and fever, estimates based on less than 72 days
      of observation result in over one fourth of individuals who should have been in
      the extreme quintiles of the morbidity distribution being misclassified, and over
      one fifth of all subjects appear (falsely) to suffer no morbidity. Estimates of
      longitudinal prevalence should be based on at least 72 days of observation.

PMID- 9620054
TI  - Re: "Epidemiology of insulin-like growth factor-I in elderly men and women. The
      Rancho Bernardo Study".

PMID- 9620055
TI  - Re: "Cancer mortality in workers exposed to phenoxy herbicides, chlorophenols,
      and dioxins. An expanded and updated international cohort study".

PMID- 9620056
TI  - In vivo comparison of the effects of inhibition of MAO-A versus MAO-B on striatal
      L-DOPA and dopamine metabolism.
AB  - Utilizing the cerebral microdialysis technique, we have compared in vivo the
      effects of selective MAO-A, MAO-B, and nonselective MAO inhibitors on striatal
      extracellular levels of dopamine (DA) and DA metabolites (DOPAC and HVA). The
      measurements were made in rats both under basal conditions and following L-DOPA
      administration. Extracellular levels of dopamine were enhanced and DA metabolite
      levels strongly inhibited both under basal conditions and following L-DOPA
      administration by pretreatment with the nonselective MAO inhibitor pargyline and
      the MAO-A selective inhibitors clorgyline and Ro 41-1049. The MAO-B inhibitor
      deprenyl had no effect on basal DA, HVA, or DOPAC levels. Nevertheless, deprenyl
      significantly increased DA and decreased DOPAC levels following exogenous L-DOPA
      administration, a finding compatible with a significant glial metabolism of DA
      formed from exogenous L-DOPA. We conclude that DA metabolism under basal
      conditions is primarily mediated by MAO-A. In contrast, both MAO-A and MAO-B
      mediate DA formation when L-DOPA is administered exogenously. The efficacy of
      newer, reversible agents which lack the "cheese effect" such as Ro 41-1049 are
      comparable to the irreversible MAO-A inhibitor clorgyline. The possible relevance
      of these findings for the treatment of Parkinson's disease is discussed.

PMID- 9620057
TI  - Striatal [18F]fluorodopa utilization after COMT inhibition with entacapone
      studied with PET in advanced Parkinson's disease.
AB  - The effect of peripheral catechol-O-methyltransferase (COMT) inhibition with
      entacapone on striatal uptake of 6-[18F]fluoro-L-dopa (FDOPA) was studied with
      PET both without and with entacapone in fifteen advanced parkinsonian patients
      and six healthy controls. Entacapone significantly enhanced the fraction of
      unmetabolized FDOPA in plasma from 16% to about 50% at 80 minutes after FDOPA
      injection in all subjects. The striatal to occipital ratios and the striatal
      FDOPA uptake, expressed as a modified decarboxylation coefficient (k3R0), was
      significantly increased in healthy controls, whereas in parkinsonian patients the
      increase was significant only in the caudate. On the other hand, the influx
      constant (Ki) decreased significantly in the caudate and putamen in parkinsonian
      patients; in healthy controls the Ki remained virtually unchanged. Effective
      peripheral COMT inhibition markedly increased the fraction of FDOPA in plasma and
      thus its availability in the brain for decarboxylation both in patients and
      control subjects. However, the change in striatal FDOPA uptake was modest in the
      advanced parkinsonian patients as compared to that in control subjects, because
      of the advanced disease, decreased storage capacity, or both.

PMID- 9620058
TI  - Polymorphisms of dopamine receptor and transporter genes and Parkinson's disease.
AB  - Disturbances of the dopamine system are involved in the pathogenesis of
      idiopathic Parkinson's disease (PD). Although genetic factors may play a role in
      the etiology of PD, there is little direct evidence implicating a specific gene.
      We conducted a study to test the hypothesis that allelic variations of the
      dopamine receptors (D2, D3, D4) and the dopamine transporter (DAT) contribute to
      the susceptibility to PD. Association analyses of 70 Japanese PD patients and the
      same number of age-matched controls did not reveal any association between
      alleles of the D2, D3 or D4 receptor genes or the DAT gene and PD. Thus, our
      results suggest that factor(s) other than allelic variations of these key
      proteins in the dopamine system contribute to the susceptibility to PD.

PMID- 9620059
TI  - Free radical scavenging properties of apomorphine enantiomers and dopamine:
      possible implication in their mechanism of action in parkinsonism.
AB  - The influence of R(-) apomorphine, S(+) apomorphine and dopamine on the oxidation
      kinetics of two polyunsaturated fatty acids (PUFA) (cholesteryl linoleate (CL)
      and Trilinolein (TL)) was investigated. The oxidation was initiated by free
      radicals generated through thermal decomposition of 2.2'-Azobis(2-methyl
      propionitrile) (AMPN) in phosphate buffer (pH 7.4) thermostated at 50 degrees C.
      The hydroperoxides formed were determined by iodine titration using a diode array
      spectrophotometer at 290nm. Both enantiomers of apomorphine as well as dopamine
      exerted an inhibitory effect. Tocopherol (alpha-tocopherol) and ascorbic acid
      were used as controls. The former inhibited while ascorbic acid facilitated the
      oxidation reaction. These results are discussed in relation with the possible
      role of oxidative injury in parkinsonism and the usefulness of apomorphine in
      elevating "on-off" episodes. On this basis, the non-dopaminergic enantiomer of
      apomorphine (S(+)-isomer) is put foward to test the importance of its radical
      scavenging properties in parkinsonism which could eventually lead to a
      therapeutic alternative with less side effects.

PMID- 9620060
TI  - ECT in Parkinson's disease. Changes in motor symptoms, monoamine metabolites and
      neuropeptides.
AB  - Electroconvulsive therapy (ECT) was given to 16 non-depressed, non-demented
      patients with advanced Parkinson's disease (PD). In all the patients an
      antiparkinsonian effect was seen, lasting for 18 months in one patient, 3-5
      months in seven patients, and a few days to four weeks in eight patients. After
      ECT the levels of homovanillic acid and neuropeptide Y in cerebrospinal fluid
      (CSF) were significantly increased. The eight patients with long lasting motor
      improvement after ECT had significantly lower CSF-3-methoxy-4-hydroxyphenylglycol
      compared to the group with short lasting improvement. Five patients developed
      transitory mental confusion after ECT. In these patients, and in no others, a
      high albumin-ratio was found already before ECT was given - an indication of
      blood CSF barrier damage. Our results suggest that ECT is valuable in patients
      with drug refractory PD or PD with intolerance to antiparkinsonian drugs.

PMID- 9620061
TI  - Antiparkinsonian actions of glutamate antagonists--alone and with L-DOPA: a
      review of evidence and suggestions for possible mechanisms.
AB  - There has been much speculation of late as to whether antagonists of glutamate
      receptors can be used to combat the motor difficulties of Parkinson's disease,
      either as monotherapy, or as polytherapy to boost the effects of conventional L
      DOPA treatment. The latter seems to be the more practical approach and the
      therapeutic implications of such treatment have been discussed in some detail.
      However, the mechanisms by which glutamate antagonists potentiate the
      antiparkinsonian actions of L-DOPA, remain cryptic. In this review we have
      explored the evidence and considered the practicality of using NMDA and non-NMDA
      receptor blockers to treat parkinsonism, as well as focusing on the ways in which
      the behavioural synergy between dopamine and glutamate systems could conceivably
      arise at the cellular level. Particular attention has been paid to the
      differential interaction between glutamate antagonists and postsynaptic dopamine
      D1 and D2 receptory mechanisms, since these are currently believed to reflect the
      activity of the two major basal ganglia output circuits: the so-called direct
      pathway to the substantia nigra and the indirect pathway to the globus pallidus.
      Finally, we have considered the new proposal, that inhibiting glutamate
      transmission in the basal ganglia accelerates the enzymic conversion of L-DOPA to
      dopamine at presynaptic sites.

PMID- 9620062
TI  - Glutamatergic regulation of striatal peptide gene expression in rats.
AB  - The mRNA levels encoding enkephalin and substance P were measured in the rat
      striatum following cortical ablation, blockade of N-methyl-D-aspartate (NMDA)
      receptors or inhibition of glutamate release by lamotrigine. Unilateral ablation
      of the cerebral cortex resulted in a decrease of substance P mRNA levels
      particularly in the rostral dorsolateral and dorsomedial striatum ipsilateral to
      the lesion. There was a similar trend for a reduction in levels of enkephalin
      mRNA. Continuous, intrastriatal infusion of the competitive NMDA receptor
      antagonist, 3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid, (CPP,
      0.12 and 1.2microg/day) decreased both enkephalin mRNA and substance P mRNA in
      dose-dependent manner evenly throughout the striatum adjacent to the infusion
      site. Following subchronic administration of the presumed glutamate release
      inhibitor, lamotrigine (5 and 20mg/kg IP) there was no significant alterations in
      either enkephalin mRNA or substance P mRNA levels in the striatum. Both
      enkephalin mRNA and substance P mRNA expression in the rat striatum appear
      tonically stimulated through postsynaptic NMDA receptor mediated mechanisms. This
      contrasts with differential dopaminergic modulation of peptides in striatal
      output neurons.

PMID- 9620063
TI  - Lamotrigine in Parkinson's disease--a double blind study.
AB  - Antiglutamatergic acting substances are considered to be useful tools for the
      treatment of hypokinesia in animal models for Parkinson's disease (PD). Moreover,
      most known antiglutamatergic compounds act postsynaptically and are either toxic
      or weak with regard to their clinical potency. The antiepileptic drug
      "Lamotrigine (LTG)" inhibits presynaptic glutamate release and may therefore
      provide a novel approach for PD therapy. Encouraging results from a pilot project
      led us to establish a placebo controlled trial including 20 patients with PD. The
      substance was generally well tolerated. There was a significant difference in the
      investigator's overall assessment of efficacy (6/10 vs. 2/10 improvement; p <
      0.05) and a tendency for LTG to exhibit a beneficial effect in some registration
      parameters, but no significant differences in motor response were found between
      the two groups. We failed to confirm that LTG mediates a strong antiparkinsonian
      effect in this small study, but to clearly demonstrate slight or moderate
      beneficial effects larger groups are required.

PMID- 9620064
TI  - Alpha-1-antichymotrypsin bi-allele polymorphism, apolipoprotein-E tri-allele
      polymorphism and genetic risk of Alzheimer's syndrome.
AB  - The alpha1-antichymotrypsin and apolipoprotein-E polymorphisms were investigated
      in patients suffering from Alzheimer's syndrome and non-demented psychiatric
      inpatients as controls. The apolipoprotein E allele 4, well known as risk factor,
      tended to be elevated in the index group. The frequency of the alpha1
      antichymotrypsin allele A was significantly increased in patients with
      Alzheimer's syndrome: 0.647 vs. 0.483 (chi-square test, p < 0.05). We conclude
      that, apart from the apolipoprotein E allele 4, the alpha1-antichymotrypsin
      allele A possibly represents a second genetic factor increasing individual's risk
      for Alzheimer's syndrome.

PMID- 9620065
TI  - Role of epidermal growth factor receptor in the metastasis of intraocular
      melanomas.
AB  - PURPOSE: To explore the expression and function of epidermal growth factor
      receptor (EGFR) expression on human uveal melanoma cells. METHODS: Five human
      uveal melanoma cell lines were examined by flow cytometry for the expression of
      EGFR. The correlation between EGFR expression and metastasis of uveal melanoma
      cells was tested in a nude mouse model of intraocular melanoma. The effect of
      EGFR on liver homing of blood-borne uveal melanoma cells was tested by tracing
      the fate of radiolabeled cells treated with anti-EGFR monoclonal antibody. The
      capacity of EGFR to inhibit the cytotoxic effects of tumor necrosis factor-alpha
      (TNF-alpha) was determined in vitro. The role of EGFR in promoting metastatic
      disease was studied by infusing intraocular melanoma-bearing mice using a
      neutralizing antibody against EGFR. RESULTS: EGFR was expressed to varying
      degrees on all eight human uveal melanoma cell lines. Expression of EGFR
      correlated with metastatic potential and capacity of blood-borne uveal melanoma
      cells to localize in the liver. EGFR rendered uveal melanoma cells resistant to
      the cytolytic effects of TNF-alpha. Blocking EGFR with a neutralizing monoclonal
      antibody increased the susceptibility of uveal melanoma cells to TNF-mediated
      cytolysis, inhibited metastases, and prolonged host survival. CONCLUSIONS: The
      expression of EGFR on five human uveal melanoma cell lines is correlated with an
      increased capacity to localize in the liver, an increased resistance to TNF
      mediated lysis, and decreased survival. Targeting EGFR expression and function
      may be a fruitful strategy for managing patients with uveal melanoma.

PMID- 9620066
TI  - Capillaries are present in Bruch's membrane at the ora serrata in the human eye.
AB  - PURPOSE: Because earlier studies indicate that the choroid close to the ora
      serrata may have unique anatomic features such as wandering cells, blood vessels
      in Bruch's membrane, and accumulated pigment in the retinal pigment epithelium
      (RPE), the morphology of the normal human eye at the ora serrata region was
      investigated. METHODS: Specimens from the ora serrata region of two normal human
      eyes (male donors, 48 and 52 years old) were investigated by light and electron
      microscope. Specimens from all quadrants were studied in one eye. RESULTS: The
      elastic layer of Bruch's membrane extended as far as 15 microm into the
      peripheral choroid; capillaries were included between the elastin layer and the
      RPE. Nasally, from the anterior end to 2 mm posterior of the ora serrata, the RPE
      cells contained more melanin than did those in the adjacent posterior region.
      Melanin granules in the RPE cells close to the ora either formed large clusters
      or appeared unusually small because of fragmentation. A unique, fine lamellar,
      membranous material with a fingerprint-like structure was found between the basal
      folds of the RPE. This material is also found within the extracellular matrix of
      the choroid and in association with red blood cells. CONCLUSIONS: The morphology
      of Bruch's membrane is varied near the ora serrata because capillaries and
      wandering cells are present in its outer collagenous layer. Unique, fine
      lamellar, fingerprint-like structures are extruded from the RPE and are removed
      from the eye together with red blood cells. Capillaries within the inner
      collagenous region of Bruch's membrane at the ora serrata may not necessarily
      represent a pathologic response but may be a normal characteristic of thick
      regions of Bruch's membrane.

PMID- 9620067
TI  - The Alabama Age-Related Macular Degeneration Grading System for donor eyes.
AB  - PURPOSE: To develop a systematic method for identifying and grading age-related
      macular degeneration (ARMD) in human donor eyes, postmortem fundus appearance was
      compared with histopathologic assessment in eyes with a spectrum of age-related
      macular change. METHODS: Eyes without grossly visible, late ARMD were obtained
      from 8 cancer patients and 26 donors older than 50 years. Postmortem fundus
      appearance was graded for drusen and pigmentary change, using stereo color
      photographs. Eyes were processed and sectioned at 1 microm for histopathologic
      evaluation of macular retinal pigment epithelium-Bruch's membrane complex. The
      histologic diagnosis was compared with gross fundus appearance, clinical
      ophthalmic histories (n = 25), and clinical fundus photographs that were graded
      using the Wisconsin Age-related Maculopathy Grading System (n = 5). RESULTS: Ten
      eyes met histopathologic criteria for early ARMD. A similar proportion of eyes
      (27%-32%) was identified as affected by ARMD by other published histopathologic
      criteria. By choosing eyes with at least one druse larger than 125 microm in
      diameter or an area of pigment-clumping 500 microm in diameter that was visible
      in the postmortem fundus, ARMD cases were identified with 90% sensitivity and 95%
      specificity. CONCLUSIONS: The Alabama ARMD Grading System permits rational and
      standardized use of donor eyes in studies that are directed toward understanding
      the pathogenesis of ARMD.

PMID- 9620068
TI  - Role of NF-kappaB-mediated interleukin-8 expression in intraocular
      neovascularization.
AB  - PURPOSE: To investigate the role of interleukin (IL)-8 in intraocular
      neovascularization and the mechanism of its production. METHODS: Interleukin-8
      was measured with enzyme-linked immunosorbent assays in vitreous and aqueous
      fluid obtained from patients with neovascular diseases. Localization of IL-8 was
      examined by immunohistochemistry. An in vitro angiogenesis assay was performed on
      collagen gels, by using bovine aortic endothelial cells to determine the effect
      of the vitreous fluid. In bovine retinal glial cells under hypoxia, NF-kappaB
      activation was evaluated by immunoblot analysis and by electrophoretic mobility
      shift assay, and IL-8 and vascular endothelial growth factor (VEGF) mRNA
      expression was determined by semiquantitative reverse transcription-polymerase
      chain reaction. RESULTS: The concentration of IL-8 in vitreous fluid of patients
      with retinal neovascularization was significantly higher than that of patients
      without neovascular disease. Interleukin-8 immunostaining was detected in
      vascular endothelial cells and glial cells in the retinas with
      neovascularization. Vitreous fluid with high concentrations of IL-8 induced
      tubular morphogenesis in endothelial cells, and this effect was inhibited to a
      similar extent by neutralizing antibodies to IL-8 or to VEGF. In glial cells, in
      vitro, hypoxia induced NF-kappaB activation and increased IL-8 and VEGF mRNA.
      Furthermore, pyrrolidine dithiocarbamate, a specific inhibitor of NF-kappaB
      activation, prevented the induction of the IL-8 gene, but not that of the VEGF
      gene. CONCLUSIONS: These results suggest that IL-8 induced by hypoxia and
      mediated by NF-kappaB may contribute to the pathogenesis of intraocular
      neovascularization.

PMID- 9620069
TI  - Light history and age-related changes in retinal light damage.
AB  - PURPOSE: To determine the effects of age and long-term light- or dark-rearing
      environments on acute, intense-light-mediated retinal degeneration. METHODS: Male
      albino rats were maintained in a dim cyclic light environment or in darkness for
      as long as 1 year. When aged 2, 4, 8, and 12 months, some rats were given the
      synthetic antioxidant dimethylthiourea (DMTU) by intraperitoneal injection and
      were exposed to intense visible light for as long as 24 hours. Uninjected control
      rats were exposed to light at the same time. Other rats were treated with light
      of lower intensity for various periods. Two weeks after intense-light treatment,
      photoreceptor cell degeneration was estimated by determining the level of
      rhodopsin and by measuring the content of photoreceptor cell DNA. Light-induced
      changes in retinal DNA were analyzed immediately after exposure by neutral gel
      electrophoresis and by 8-hydroxy-deoxyguanosine measurements. Expression of the
      antioxidative stress protein heme oxygenase-1 (HO-1) was determined by northern
      blot analysis of mRNA in retinal extracts. RESULTS: At all ages, rats reared in
      cyclic dim-light conditions had lower rhodopsin levels than did rats reared in
      darkness; photoreceptor cell DNA levels were unaffected by the rearing
      environment. Senescent losses in rhodopsin and retinal DNA were significant after
      rats were 12 months old. Dim-light-reared rats exhibited an age-related increase
      in retinal light damage susceptibility, whereas dark-reared rats were equally
      susceptible to damage at all ages. In both types of rats, the mechanism of light
      induced cell death involved an apoptotic process, visualized by the pattern of
      DNA fragments on electrophoretic gels. The process also induced the expression of
      HO-1 mRNA. Photoreceptor cell loss determined by biochemical measurement, DNA
      fragmentation, and HO-1 induction were dramatically reduced by the administration
      of DMTU. CONCLUSIONS: The age-related increase in susceptibility to retinal light
      damage in rats is influenced by their long-term daily light history. Decreasing
      retinal irradiance by dark-rearing eliminates the age-related increase in light
      damage, suggesting a correlation between light environment and retinal gene
      expression associated with damage. In all rats, retinal light damage resulted in
      a pattern of DNA fragmentation consistent with apoptotic cell death and in an
      increased expression of HO-1 mRNA. Antioxidant treatment greatly reduced
      apoptosis and HO-1 expression. This indicates that light damage involves an
      oxidative process that may also trigger apoptosis in the retina. The rat aging
      model may provide useful insights into the role of light environment associated
      with retinal degeneration in an aging human population.

PMID- 9620070
TI  - Expression of degradative enzymes and protease inhibitors in corneas with
      keratoconus.
AB  - PURPOSE: Keratoconus is characterized by thinning and scarring of the central
      region of the cornea. Previous research showed that, in corneas obtained from
      patients with keratoconus, lysosomal enzyme activities are elevated, whereas
      levels of protease inhibitors such as alpha1-proteinase inhibitor are reduced.
      This study was undertaken to examine further the expression of a spectrum of
      proteolytic enzymes and protease inhibitors. METHODS: Corneal buttons were
      collected from patients with keratoconus, healthy subjects, and patients with
      other corneal diseases. Immunohistochemical staining was performed on paraffin
      sections. Enzymatic assays and western blot analysis were carried out for
      cathepsins B and G. In addition, an in situ zymography procedure was used to
      examine the gelatin- and casein-digesting activities in corneas with keratoconus.
      RESULTS: An enhanced staining was found with antibodies to cathepsins B and G.
      Enzymatic assays and western blotting confirmed that the levels of these two
      enzymes were elevated in corneas with keratoconus. No alteration was noted with
      any of the matrix metalloproteinase (MMP) family members and other enzymes and
      inhibitors examined, although in situ zymography did indicate an increase in net
      gelatin- and casein-digesting activities in corneas with keratoconus. These
      activities were mostly abolished by inhibitors for serine and cysteine
      proteinases, but not by those for MMPs and aspartic proteinases. CONCLUSIONS:
      Levels of cathepsins B and G are increased in corneas with keratoconus. These
      enzymes may contribute to the heightened in situ gelatin- and casein-digesting
      activities, leading to abnormalities in keratoconus.

PMID- 9620071
TI  - Circumcorneal annulus of collagen fibrils in the human limbus.
AB  - PURPOSE: To quantify the orientation of the collagen fibrils in the human limbus
      and to compare it with the orientation in the cornea and the sclera. METHODS:
      Fibril orientation was measured from 100 synchrotron x-ray diffraction patterns
      collected at intervals along lines across the cornea, limbus, and sclera.
      RESULTS: A distinct circumcorneal annulus of collagen fibrils was revealed in the
      limbus. For the individual cornea investigated, the annulus was not uniform
      around the corneal circumference; its width, fibril angular spread, and fibril
      density all varied with position. The average width of the annulus was narrower
      in the superior sector (1.5 mm) than in the inferior sector (2.0 mm). The results
      from the edge of the cornea suggested that the preferentially aligned corneal
      fibrils bend sharply at the limbus to run circumferentially or that, together
      with this bending or alone, extra fibrils arising in the sclera run across this
      zone. In the cornea the biaxial preferred directions became more pronounced from
      the center of the cornea toward the limbus along the superior-inferior axis.
      CONCLUSIONS: The excess of circumferential fibrils in the limbus, predicted from
      the sharp change of curvature in the surface of the eye at the limbus, appeared
      to take the form of a well-defined annulus. From a consideration of the mechanics
      of the system it seemed probable that the purpose of this annulus was to help
      maintain the correct curvature of the cornea. Before further research, it was
      hypothesized that some refractive problems associated with an incorrect curvature
      of the cornea may be related in part to abnormalities of this circumcorneal
      annulus.

PMID- 9620072
TI  - Expression of tenascin-C splice variants in normal and bullous keratopathy human
      corneas.
AB  - PURPOSE: To characterize the expression patterns of tenascin-C (TN-C) splice
      variants in normal corneas and in those affected by pseudophakic-aphakic bullous
      keratopathy (PBK-ABK). METHODS: Alternatively spliced variants of TN-C mRNA from
      normal and age-matched human corneas with PBK-ABK were analyzed by
      semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and
      Southern blot hybridization, using beta2-microglobulin as a housekeeping gene to
      normalize the samples. Normal and PBK-ABK corneas were studied by
      immunofluorescence and western blot analysis with antibodies to specific
      fibronectin type III-like (FN-III) repeats of TN-C. RESULTS: Tenascin-C mRNA
      expression was detected in epithelial, stromal, and endothelial cells of normal
      and PBK-ABK central corneas, although the protein was seen only in diseased
      corneas. Assessed by RT-PCR, PBK-ABK corneas expressed approximately three times
      more total TN-C mRNA than did normal corneas. Four major TN-C mRNA variants (with
      no FN-III insertional repeats or with retained insertional repeats D, A1, or
      A1+D) and three minor variants (with retained repeats A1+A2, A1+A2+D, or
      A1+A2+B+D) were much more abundant in PBK-ABK than in normal corneas. Repeat A1
      was more abundant in PBK-ABK TN-C protein than repeats A2, A3, B, or D. Major TN
      C variants in PBK-ABK corneas were in the range of 190 kDa to 240 kDa.
      CONCLUSIONS: Expression of TN-C mRNA and protein is higher in PBK-ABK corneas
      than in normal corneas. This increase mainly concerns relatively small TN-C
      splice variants that may affect corneal cell adhesion and migration and
      contribute to the exacerbation of PBK-ABK.

PMID- 9620074
TI  - Multifocal rod electroretinograms.
AB  - PURPOSE: To assess the feasibility of obtaining reliable multifocal rod
      electroretinograms (ERGS) and to compare them to full-field ERGs. METHODS:
      Multifocal rod ERGs were recorded using a stimulus array of 61 hexagons. The
      minimum number of dark, blank frames between flashes was varied from 0 (a minimum
      of 13.3 msec between flashes) to 21 (a minimum of 293 msec between flashes). Full
      field ERGs were obtained using trains of flashes designed to simulate the
      multifocal sequences. Flashes were blue (W47B), except in a few cases in which
      red (W26) was used to check for cone intrusion. Flash intensities varied from -1
      to 1.7 log scot td-s. RESULTS: Dark-adapted, multifocal ERGs to blue flashes had
      a small, early component followed by a larger, late component. The early
      component showed little change in amplitude with increasing intensity.
      Comparisons with the full-field ERGs indicated that the early component was the
      focal response. The larger, late component was the response to stray light, and
      it can be suppressed with the addition of a surround. The focal response was from
      a relatively circumscribed retinal region. This is shown by comparing the
      multifocal rod responses from a patient with retinitis pigmentosa to her
      behaviorally measured rod visual field. CONCLUSIONS: By choosing conditions
      (namely, flashes of moderate intensity with a surround) to minimize the effects
      of stray light, multifocal rod ERGs can be recorded with sufficient localization
      to be clinically useful. However, the signal-to-noise ratio of these multifocal
      rod ERGs was poorer than for multifocal cone responses for comparable recording
      periods because of the need for blank frames and the slower recovery of the rods
      to successive presentations.

PMID- 9620073
TI  - Properties of whole-cell ionic currents in cultured human corneal epithelial
      cells.
AB  - PURPOSE: To identify and partially characterize the ionic currents contributing
      to the whole-cell conductance of cultured human corneal epithelial cells.
      METHODS: Epithelial cells were scraped from human donor corneas and cultured for
      use in patch-clamp experiments. Amphotericin B and the perforated-patch
      configuration were used to measure whole-cell currents in cells isolated from
      confluent monolayers. RESULTS: Cell monolayers exhibited cobblestone morphology
      and were immunopositive for corneal epithelium-specific cytokeratin. Single cells
      had a capacitance of 21 +/- 2 pF and expressed similar types of ionic currents
      regardless of passage number. In descending order of frequency of occurrence,
      cells exhibited a nonselective cation current active at depolarized voltages and
      insensitive to Ba2+ and Gd3+; an outwardly rectifying K+ current active at
      depolarized voltages, stimulated by flufenamic acid and inhibited by
      tetraethylammonium; a voltage-gated inward Na+ current; an outwardly rectifying
      K+ current active at hyperpolarized voltages, stimulated by flufenamic acid,
      blocked by Ba2+, and insensitive to diltiazem; an inwardly rectifying K+ current;
      and a nonselective cation current inhibited by flufenamic acid. CONCLUSIONS: Our
      results are consistent with those in previous studies of noncultured epithelia
      from rabbit and human corneas showing an outwardly rectifying K+ current active
      at hyperpolarized voltages and a nonselective cation current active at
      depolarized voltages and insensitive to Ba2+. These data suggest cultured cells
      may be useful in determining the physiological role of ion channels in corneal
      epithelia and may aid in the development of a cell-based model for the
      examination of the effects of wounding and toxic agents on the human cornea.

PMID- 9620075
TI  - A therapeutic vaccine that reduces recurrent herpes simplex virus type 1 corneal
      disease.
AB  - PURPOSE: To investigate the therapeutic efficacy of periocular vaccination with
      herpes simplex virus (HSV) recombinant glycoprotein D from HSV-1 (gD1) or HSV-2
      (gD2) in decreasing HSV-induced recurrent dendritic keratitis and HSV-induced
      recurrent ocular shedding in rabbits latently infected with HSV-1. METHODS:
      Rabbits latently infected with HSV-1 were vaccinated periocularly (by
      subconjunctival injection) with gD1 and adjuvant, gD2 and adjuvant, or adjuvant
      alone. Eyes were examined daily for 49 days for recurrent herpetic keratitis and
      for recurrent infectious HSV-1 shedding. RESULTS: In both vaccinated groups, a
      significantly decreased number of eyes exhibited recurrences of herpetic
      keratitis compared with recurrences in adjuvant-treated control eyes (gD1 group,
      27/1372, [2%]; gD2 group, 24/1274, [2%]; and control, 54/1274 [4%]; P < 0.005).
      Eyes in the gD1-vaccinated group (44/1308 [3.4%]; P = 0.01), but not those in the
      gD2-vaccinated group (71/1274 [5.6%]; P = 0.93), had significantly decreased
      viral shedding (positive cultures compared with total cultures) compared with
      eyes in the adjuvant-treated control group (69 of 1275 [5.4%]). CONCLUSIONS:
      Recurrent HSV-1 corneal disease was significantly reduced by therapeutic local
      periocular vaccination. The vaccine may be more efficacious against HSV-1-induced
      recurrent corneal disease than against recurrent HSV-1 ocular shedding. Its
      efficacy against corneal disease appeared to be longer lasting than its efficacy
      against recurrent spontaneous shedding. The heterotypic gD2 vaccine was as
      efficacious as the homotypic gD1 vaccine against recurrent corneal disease,
      whereas the homotypic vaccine was much more efficacious than the heterotypic
      vaccine against recurrent HSV-1 shedding. This is the first report in any animal
      model of a successful therapeutic vaccine against recurrent HSV-1-induced corneal
      disease. These results support the concept that development of a therapeutic
      vaccine for ocular HSV-1 recurrence in humans may be possible.

PMID- 9620076
TI  - Effects of drug therapy on Toxoplasma cysts in an animal model of acute and
      chronic disease.
AB  - PURPOSE: To evaluate the effects of drug therapy on the clinical course of acute
      acquired Toxoplasma retinochoroiditis and on the number of Toxoplasma cysts
      present in the brain and ocular tissues in the hamster animal model. METHODS: The
      Syrian golden hamster animal model of Toxoplasma retinochoroiditis was used. In
      acute disease, systemically administered atovaquone was compared with
      conventional therapies (pyrimethamine combined with sulfadiazine; clindamycin;
      and spiramycin). The clinical course of the ocular disease was determined with
      retinal examination and photography of the fundus. The number of Toxoplasma cysts
      remaining after treatment was evaluated in aliquots of brain homogenate and in
      retinal tissue. The effect of atovaquone on cerebral Toxoplasma cyst count was
      also studied in chronic disease. RESULTS: None of the drugs administered altered
      the course of the acute disease, judged by clinical examination. Atovaquone alone
      significantly reduced the number of cerebral Toxoplasma cysts after acute
      disease. Atovaquone also significantly reduced the cerebral Toxoplasma cyst count
      in chronic disease. CONCLUSIONS: Tissue cysts are believed to be responsible for
      reactivation of Toxoplasma retinochoroiditis. Atovaquone has the potential to
      reduce the risk of recurrent disease.

PMID- 9620077
TI  - The role of eosinophils and neutrophils in helminth-induced keratitis.
AB  - PURPOSE: Intrastromal injection of mice with antigens from the parasitic helminth
      that causes river blindness (Onchocerca volvulus) induces eosinophil recruitment
      to the corneal stroma at the time of maximum corneal opacification and
      neovascularization. The present study was conducted to examine the role of
      eosinophils and neutrophils in onchocercal keratitis in control C57Bl/6 mice and
      in interleukin-5 gene knockout (IL-5(-/-)) mice. METHODS: C57Bl/6 and IL-5(-/-)
      mice were immunized subcutaneously and injected intrastromally with soluble O.
      volvulus antigens. Mice were killed at various times thereafter. Development of
      keratitis was assessed by slit lamp examination, and inflammatory cells in the
      cornea were identified by immunohistochemistry. RESULTS: A biphasic recruitment
      of inflammatory cells was observed in C57Bl/6 mice; neutrophils predominated
      during the first 72 hours after intrastromal injection and subsequently declined,
      whereas eosinophil recruitment increased as time elapsed and comprised the
      majority (90%) of cells in the cornea by day 7. In contrast, neutrophils were the
      predominant inflammatory cells in IL-5(-/-) mice at early and late time points
      and were associated with extensive stromal damage and corneal opacification and
      neovascularization. Eosinophils were not detected in these mice at any time.
      CONCLUSIONS: In the absence of eosinophils, neutrophils can mediate keratitis
      induced by helminth antigens. Together with the early neutrophilic infiltrate in
      control animals, these observations indicate that neutrophils have an important
      role in onchocercal keratitis.

PMID- 9620078
TI  - Cytomegalovirus glycoprotein B genotyping in ocular fluids and blood of AIDS
      patients with cytomegalovirus retinitis.
AB  - PURPOSE: To determine the frequency of cytomegalovirus glycoprotein B (gB)
      genotypes in clinical samples of ocular fluids of patients with acquired immune
      deficiency syndrome (AIDS) who have cytomegalovirus retinitis and to compare
      these with the cytomegalovirus gB genotype in paired peripheral blood leukocytes.
      METHODS: Glycoprotein B genotypes of cytomegalovirus genomic DNA were determined
      in 29 ocular and 9 paired blood samples of 27 patients, by polymerase chain
      reaction amplification followed by restriction fragment length polymorphism
      analysis. RESULTS: In the 29 ocular samples, 30 gB genotypes were determined:
      Glycoprotein B1 was found in 8 samples (27%), gB2 in 9 samples (30%), gB3 in 6
      samples (20%), and gB4 in 3 samples (10%). In one sample, a mixed genotype was
      observed. In addition to these previously characterized gB genotypes, a new gB
      variant was observed in the ocular fluid of four patients. Partial sequence
      analysis revealed that this new gB genotype is closely related to gB3, and it was
      therefore named gB3'. In the blood samples, only gB1, gB2, and gB3 genotypes were
      observed. In the nine paired samples of ocular fluid and blood, four showed a
      difference in gB genotype between these compartments. CONCLUSIONS: The
      distribution of cytomegalovirus glycoprotein B genotypes gB1-gB4 in ocular fluids
      of patients with AIDS who have cytomegalovirus retinitis was determined in this
      study. The predominance of gB2, as described by others, was not confirmed. The
      glycoprotein B genotype in the eye can be different from the genotype found in
      the blood of the same patient. A new gB variant, gB3', was found in the ocular
      samples of 4 of 27 patients, but not in the blood samples tested.

PMID- 9620079
TI  - The aqueous humor is capable of generating and degrading H2O2.
AB  - PURPOSE: To determine the ability of the aqueous humor to generate and degrade
      H2O2, the effect of environmental factors such as oxygen tension and temperature,
      and the constituents contributing to the observed results. METHODS: Aqueous humor
      was carefully removed from bovine eyes within 3 hours of death. Standard and new
      techniques were used to follow H2O2 degradation and formation. Catalase activity
      was measured by H2O2 decomposition, usually at 100 microM and 10 mM H2O2, and in
      some cases by O2 generation. RESULTS: Bovine aqueous humor generated and degraded
      H2O2. The generation of H2O2 was minimal at 0 degrees C but increased as
      temperature increased, so that at 37 degrees C at 3 hours, approximately 90
      microM H2O2 was observed. Degradation was more complex. At 0 degrees C, only a
      slow rate of degradation was observed. At 25 degrees C, it was more rapid, and a
      steady state between generation and degradation was observed at approximately 30
      microM. However, at 37 degrees C, starting with 100 microM H2O2, degradation was
      initially rapid, but then generation became predominant and H2O2, concentration
      increased to more than 100 microM in 3 hours. No H2O2 was generated in the
      absence of O2, and H2O2 production increased with increasing O2 tension. Both low
      and high molecular weight components contributed to the degradation, but
      synthesis was completely dependent on low molecular weight constituents. Ascorbic
      acid and metal ions such as Cu+ made a major contribution to H2O2 production.
      Catalase may be the macromolecular component responsible for aqueous H2O2 decay,
      as evidenced by H2O2 degradation, inhibition by boiling or 3-aminotriazole, and
      the approximate correspondence between oxygen generation and H2O2 degradation.
      CONCLUSIONS: The results indicate that the aqueous humor is capable of producing
      levels of H2O2 that have been shown previously to cause cataract in organ
      culture. Changes in aqueous humor metal ion content and concentration of oxygen
      level have profound effects on H2O2 concentration and may effect lens viability.
      The variation in published H2O2 levels may in part be the result of the
      conditions under which the aqueous humor was obtained, stored, and used for
      assay. The observed steady state H2O2 concentration of 1 microM in fresh aqueous
      from bovine eyes must be maintained by the metabolism of surrounding tissues as
      well as intrinsic components capable of degrading H2O2.

PMID- 9620080
TI  - Structural changes in lenses of mice lacking the gap junction protein connexin43.
AB  - PURPOSE: To investigate the role of the gap junction protein connexin43 (Cx43),
      which is predominantly expressed in lens epithelial cells in the control of lens
      development and organization. METHODS: Newborn mice in which the Cx43 gene was
      disrupted by homologous recombination were used. Lenses from Cx43 (-/-) mice and
      wild-type littermates were processed by using 2% glutaraldehyde fixation for
      light and transmission electron microscopy and by freezing in liquid nitrogen for
      light and confocal microscopy of immunofluorescence in cryosections. RESULTS: In
      wild-type mice, Cx43 was immunolocalized to apical and lateral regions of lens
      epithelial cells and throughout the cornea, iris, ciliary body, and retina. In
      the bow, or equatorial, region of the lens, Cx43 disappeared gradually at the
      margins of the epithelial layer, whereas major intrinsic polypeptide, MP26, and
      alpha-crystallins were only detected in differentiated fiber cells.
      Ultrastructural studies revealed that epithelial cells and epithelial fiber cells
      were connected by large gap junctions. Lens fiber cells were closely apposed to
      apical boundaries of epithelial cells and apposed to one another along their
      entire lengths. In Cx43 (-/-) mice, epithelial cells were connected more loosely.
      The distribution of MP26 and alpha-crystallin in bow region fiber cells in Cx43 (
      /-) lenses was not distinguishable from that in the lenses of wild-type mice.
      Cx46 and Cx50 were also expressed in superficial and cortical fiber cells, with
      similar distributions in Cx43 (-/-) and wild-type mice. However, organization of
      appositional membranes between lens fiber cells and between fiber and epithelial
      cells differed dramatically in the Cx43 (-/-) lens. In contrast to the close
      apposition of cells in lenses of normal mice, fiber cells in Cx43 (-/-) lenses
      were largely separated from apical surfaces of epithelial cells, and large
      vacuolar spaces were apparent between fiber cells, most prominently in deeper
      cortical regions. CONCLUSIONS: The normal differentiation of lens fiber cells in
      the bow region in lenses of Cx43 (-/-) mice, evidenced by similar distributions
      of Cx46, Cx50, MP26, and alpha-crystallin, suggests that the expression of Cx43
      is not required for this process. However, these lenses exhibit grossly dilated
      extracellular spaces and intracellular vacuoles, indicative of early stages of
      cataract formation. These changes suggest that osmotic balance within the lens is
      markedly altered in Cx43 (-/-) animals, highlighting the importance of
      intercellular communication mediated by lens epithelial Cx43 gap junctions in the
      function of this tissue.

PMID- 9620081
TI  - Noninvasive investigations of the normal ocular circulation in humans.
AB  - PURPOSE: To compare the reproducibility of laser interferometric measurements of
      fundus pulsation, pneumatonometric measurement of pulse amplitude (PA) and
      pulsatile ocular blood flow (POBF), and Doppler ultrasonic measurements of blood
      flow velocity in the ophthalmic artery (OA) and the posterior ciliary arteries
      (PCAs) and to investigate the association of the results obtained with these
      methods and to characterize ocular hemodynamics during Valsalva maneuver and
      isometric handgrip. METHODS: All studies were performed in healthy subjects.
      Fundus pulsation (n = 48), POBF (n = 24), and blood flow velocities (n = 24) were
      measured at baseline and during the Valsalva maneuver and isometric handgrip.
      Intraclass correlation coefficients were calculated for test/retest variability,
      for short-term variability, and for interobserver variability. RESULTS:
      Intraclass correlation coefficients were between 0.95 and 0.98 for fundus
      pulsation measurements, between 0.54 and 0.76 for pneumatonometric measurements,
      between 0.44 and 0.88 for Doppler sonographic measurements in the OA and between
      0.32 and 0.60 in the PCAs. There was a high degree of association between
      pneumatonometric parameters and fundus pulsation amplitude. Valsalva maneuver
      significantly reduced fundus pulsations, PA, and POBF, whereas isometric
      handgripping did not change these parameters. CONCLUSIONS: The reproducibility of
      fundus pulsation measurements was excellent. Reproducibility of pneumatonometric
      parameters and ultrasonographic measurements in the OA was satisfactory.
      Reproducibility of ultrasonographic measurements in the PCAs was low. Data
      obtained during the autonomic stimuli experiments argue against the sole use of
      systems to measure pulsatile blood flow, if no additional data on flow
      pulsatility are available. At least in cases when changes in blood pressure are
      likely to occur the ratio of pulsatile to nonpulsatile blood flow might not be
      constant and POBF might not be an adequate measure of total ocular blood flow.

PMID- 9620082
TI  - Existence of a p-glycoprotein drug efflux pump in cultured rabbit conjunctival
      epithelial cells.
AB  - PURPOSE: To determine whether a p-glycoprotein (P-gp) drug efflux pump exists in
      cultured rabbit conjunctival epithelial cells (RCEs) to restrict the absorption
      of cyclosporin A (CSA) and other lipophilic drugs such as verapamil and
      dexamethasone. METHODS: The anti-P-gp monoclonal antibody (mAb) C219 was used in
      western blot analysis to reveal the presence of P-gp in freshly isolated and
      cultured RCEs. Bidirectional transport of tritiated CSA, verapamil, and
      dexamethasone (0.5 or 5.0 microM) across cultured RCEs was evaluated in the
      absence and presence of P-gp inhibitors and an external mAb to P-gp (4E3).
      RESULTS: Western blot analysis of lysates of freshly isolated and cultured RCEs
      with C219 mAb revealed a 170-kDa membrane protein band. At 0.5 microM CSA, the
      basal-to-apical (ba) apparent permeability coefficient (P(app) that is, efflux)
      was 9.3 times higher than that in the apical-to-basal direction (that is,
      influx). At 5 microM, this ratio was halved. Net CSA secretion was blocked
      completely at 4 degrees C. Verapamil (100 microM), progesterone (100 microM) and
      4E3 mAb (5 microg/ml) increased CSA influx three times, while reducing efflux by
      50% to 70%. Verapamil and progesterone inhibited CSA efflux in a concentration
      dependent manner. In all cases, net secretory CSA flux was markedly reduced. The
      P(app) for verapamil (0.5 microM) and dexamethasone (0.5 microM) in the ba
      direction was 3.4 and 1.6 times, respectively, which was higher than that in the
      opposite direction. The 4E3 mAb reduced net verapamil secretion by 65%.
      CONCLUSIONS: There may exist a P-gp-mediated drug efflux pump on the apical
      aspect of the rabbit conjunctiva to restrict the absorption of cyclosporin A and
      other lipophilic drugs.

PMID- 9620083
TI  - Protective effects of FK506 against glutamate-induced neurotoxicity in retinal
      cell culture.
AB  - PURPOSE: To examine the effects of FK506 on glutamate neurotoxicity in cultured
      retinal neurons. METHODS: Experiments were performed with primary retinal
      cultures obtained from 17- to 19-day-old rat fetuses. To assess the effects of
      FK506 and other drugs on glutamate neurotoxicity, cultures were treated with a
      drug beginning 10 minutes before application of glutamate and continuing during
      the subsequent 10 minutes of glutamate exposure. The treated cells were then
      incubated for 1 hour in a drug-free and glutamate-free medium. After a 1-hour
      incubation, cell viability was quantitatively measured by the trypan blue
      exclusion method. RESULTS: Brief exposure to glutamate markedly decreased cell
      viability. FK506 protected against glutamate neurotoxicity in a dose-dependent
      manner. Rapamycin is a competitive inhibitor of FK506 that binds FK506 binding
      protein. Simultaneous application of rapamycin and FK506 negated the protective
      effects of FK506. Cyclosporin A, which binds and inhibits calcineurin, mimicked
      the protective effects of FK506. Treatment with FK506 did not affect the
      intracellular maximum Ca2+ concentration induced by glutamate application.
      Although FK506 exhibited protective action against Ca2+ ionophore-induced
      neurotoxicity, it had no effect on nitric oxide-induced neurotoxicity. Treatment
      with FK506 reduced the activity of nitric oxide synthase (NOS). CONCLUSION: FK506
      protected against glutamate neurotoxicity by inhibiting NOS activity in cultured
      retinal neurons.

PMID- 9620084
TI  - Influence of intravitreal injections of HPMPC and related nucleoside analogues on
      intraocular pressure in guinea pig eyes.
AB  - PURPOSE: Cidofovir (HPMPC) is a potent long-acting anticytomegalovirus agent. In
      humans, its dose-limiting intravitreal toxicity results in the lowering of
      intraocular pressure (IOP). The purpose of the present study was to determine the
      effects of HPMPC and various acyclic nucleoside phosphonate (ANP) analogues when
      administered intravitreally in guinea pig eyes and to establish the structural
      and functional relation of these compounds in connection with their effects on
      the ciliary body and retina. METHODS: Ninety-six guinea pig eyes were injected
      with various doses of HPMPC and ANP analogues. RESULTS: Severe lowering of IOP
      with structural alterations of the ciliary body was observed when doses were
      administered that achieved final intravitreal concentrations greater than 25
      microg/ml HPMPC, 200 microg/ml cyclic HPMPC (cHPMPC), 25 microg/ml (S)-HPMPA, and
      625 microg/ml PMEG. Concentrations of 25 microg/ml HPMPC, 200 microg/ml cHPMPC or
      less, and all concentrations of (R)-HPMPA, HPMPU, PMEA, PMEC, PMEDAP, (R)-PMPA,
      and (S)-PMPA did not lower IOP significantly, nor did they cause significant
      histologic changes. CONCLUSIONS: Of the HPMP series, the cyclic analogue of HPMPC
      (cHPMPC) and HPMPC are the least toxic of the compounds that show potent anti
      human cytomegalovirus activity (HCMV). PMEG, the most potent anti-HCMV compound
      of the PME series, is toxic at higher doses. Further evaluation of lower doses is
      needed. Compounds of the PMP series are not toxic, but they show no anti-HCMV
      activities. The IOP-lowering effect of these compounds appears to be associated
      with an effect on the ciliary body.

PMID- 9620085
TI  - The localization of guanylyl cyclase-activating proteins in the mammalian retina.
AB  - PURPOSE: To explore the distribution of guanylyl cylase-activating proteins 1 and
      2 (GCAP1 and GCAP2) in the mammalian retina. METHODS: Cryostat and vibratome
      vertical sections and wholemount retinas from mouse, rat, cat, bovine, monkey,
      and human eyes were prepared for immunocytochemistry and viewing by light and
      confocal microscopy. RESULTS: In all mammalian retinas investigated, intense
      GCAP1 immunoreactivity (GCAP1-IR) was seen in cone photoreceptor inner and outer
      segments, cell bodies, and synaptic regions. Intensity of the GCAP1-IR was strong
      in inner segments of rods in all species but weaker in outer segments
      particularly so in primates and cats. GCAP2 immunoreactivity (GCAP2-IR) was weak
      in bovine, mouse, and rat cones but was intense in human and monkey cones. In all
      species except primates, GCAP2 staining was intense in rod inner and outer
      segments. In primates GCAP2-IR was intense in the rod inner segment but faint in
      the rod outer segment. A striking difference from the GCAP1 pattern of
      immunoreactivity was seen with GCAP2 antibodies as far as the inner retina was
      concerned. GCAP2-IR was evident in certain populations of bipolar, amacrine, and
      ganglion cells in all species. CONCLUSIONS: GCAP1 and GCAP2, which are involved
      in Ca2+-dependent stimulation and inhibition of photoreceptor guanylyl cyclase,
      can be detected in mammalian photoreceptor inner and outer segments, consistent
      with their physiological function. The occurrence of both GCAPs in the synaptic
      region of the photoreceptors indicates participation of these proteins in
      pathways other than regulation of phototransduction. The occurrence of GCAP2 in
      inner retinal neurons is indicative of second-messenger chemical transduction,
      possibly in metabotropic glutamate, gamma-aminobutyric acid (GABA) receptor, and
      nitric oxide-activated neural circuits.

PMID- 9620086
TI  - Lipoteichoic acid as an inducer of acute uveitis in the rat.
AB  - PURPOSE: To examine the capacity of lipoteichoic acid (LTA) to induce intraocular
      inflammation in the rat. METHODS: LTA obtained from Staphylococcus aureus and
      three different streptococcal species were suspended in saline solution in
      various concentrations and were injected into one footpad of female Lewis rats.
      The uveitic changes were assessed by conventional clinical and histopathologic
      procedures, whereas the intensity of inflammation in the anterior chamber (AC)
      was evaluated by the measurement of protein concentration and cell density in the
      aqueous humor (AH). RESULTS: LTA from S. aureus induced a strong intraocular
      inflammation between 24 and 30 hours after injection. The inflammatory reaction
      was observed in a dose-dependent manner. At a dose of 15 mg/kg LTA, the protein
      concentration and cell counts in the AH were 5.6 +/- 0.5 mg/ml and 4075 +/- 1193
      cells/microl, respectively. When LTAs of streptococcal origin were used, cells
      were undetected in the AH and protein concentration increased only two- or
      threefold compared with the control group. In pathologic examination,
      inflammatory cells were found in the AC and posterior chamber only after the
      injection of S. aureus LTA. In systemic evaluations of the liver, kidney, spleen,
      heart, lung, gut, brain, joint, and eye performed 6, 24, and 48 hours after the
      challenge, inflammatory lesions were found only in the eye. CONCLUSIONS: LTA,
      especially of S. aureus origin, induces anterior uveitis in the rat. This model
      may be useful for investigation of Gram-positive bacterial infection and uveitis.

PMID- 9620087
TI  - Matrix metalloproteinases and their inhibitors in human vitreous.
AB  - PURPOSE: To conduct zymographic analysis to study the matrix metalloproteinases
      (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) in vitreous samples of
      patients undergoing pars plana vitrectomy as part of the treatment of
      vitreoretinal disease. METHODS: Forty-two vitreous samples were collected at the
      time of pars plana vitrectomy. Diagnoses included severe (exudative) age-related
      macular degeneration (AMD) (12), macular hole (10), presumed ocular
      histoplasmosis syndrome (6), proliferative diabetic retinopathy (PDR) (5),
      epiretinal membrane (4), vitreomacular traction syndrome (2), macroaneurysm with
      subretinal hemorrhage (1), central retinal vein occlusion with vitreous
      hemorrhage (1), and proliferative vitreoretinopathy (1). Gelatin zymography,
      reverse gelatin-zymography, carboxymethylated transferrin zymography, and sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis were performed on the liquid
      vitreous samples to assess for MMP and TIMP activity. RESULTS: Progelatinase A
      occurred in all vitrectomy samples. In addition, a band consistent with TIMP-2
      occurred in all samples on reverse zymography. An inhibitor of MMP of a lower
      molecular weight than TIMP-1 was found in all the samples. A serine proteinase
      with a broad band around 180 kDa was found in 2 of the 11 AMD vitreous samples. A
      75-kDa metalloproteinase was found in several AMD samples, but it was much more
      abundant in the PDR samples. CONCLUSIONS: Metalloproteinases and their endogenous
      inhibitors are present in human vitreous and may be involved in the pathogenesis
      of PDR and other vitreoretinal diseases.

PMID- 9620088
TI  - Polymerase chain reaction analysis of corneal epithelial and tear samples in the
      diagnosis of Acanthamoeba keratitis.
AB  - PURPOSE: Acanthamoeba is an uncommon cause of corneal infection in which the best
      visual outcome follows prompt diagnosis and a long course of appropriate
      antimicrobial therapy. Because conventional detection techniques for Acanthamoeba
      have certain limitations, we investigated the ability of the polymerase chain
      reaction (PCR) to confirm the clinical diagnosis of Acanthamoeba keratitis, with
      the ultimate aim of achieving early diagnosis. METHODS: Using two different pairs
      of primers, PCR was performed on representative cultured Acanthamoeba isolates to
      confirm the assay's ability to amplify Acanthamoeba DNA from a wide range of
      acanthamoebae. Subsequently, corneal epithelial samples from 19 patients and tear
      samples from 12 patients with Acanthamoeba keratitis were analyzed by PCR for the
      presence of Acanthamoeba DNA. RESULTS: Acanthamoeba DNA was amplified by PCR from
      16 (84%) of 19 corneal epithelial samples, whereas Acanthamoeba was cultured from
      10 samples (53%), all of which were PCR positive. Tear samples from 8 (66%) of 12
      patients were positive on PCR testing, and one tear sample was PCR positive,
      whereas the corresponding epithelial biopsy had yielded a negative PCR result.
      Samples from culture-positive patients were positive on PCR testing more
      frequently than those from culture-negative patients (10/10 culture-positive
      corneal epithelial and 5/7 [71%] culture-positive initial tear samples versus 6/9
      [66%] culture-negative corneal epithelial and 2/5 [40%] culture-negative tear
      samples). All control epithelial (n = 15) and tear (n = 15) samples yielded
      negative results. CONCLUSIONS: PCR was a more sensitive diagnostic test than a
      culture for Acanthamoeba keratitis, and the use of two different primers achieved
      better sensitivity than a single set. A PCR of a tear sample also may be a useful
      complementary test and, in combination with PCR of epithelial samples, would
      prove particularly helpful in confirming the clinical diagnosis in culture
      negative cases.

PMID- 9620089
TI  - A Rho-associated protein kinase: differentially distributed in limbal and corneal
      epithelia.
AB  - PURPOSE: The authors have developed monoclonal antibodies (mAbs) to characterize
      the sequential biochemical changes in corneal epithelial cells after they
      differentiate from stem cells, located in the limbus, and migrate centripetally
      to follow the pathway of terminal differentiation. The purpose of this study was
      to identify a protein (recognized by mAb HE1/11F) with increased expression
      associated with the transition of the limbal epithelium to corneal epithelium.
      METHODS: The distribution and identification of the protein(s) were performed
      using an indirect immunohistochemical staining technique and a western blot
      analysis, respectively. A rabbit corneal epithelial cDNA library, constructed in
      the Uni-Zap XR vector, was screened with mAb HE1/11F to select cDNA clones
      expressing polypeptide(s) recognized by this mAb. Additional overlapping cDNA
      clones were obtained from a primer extension cDNA library to determine the
      sequence of the complete open reading frame encoding the protein recognized by
      mAb HE1/11F. RESULTS: Rabbit corneal epithelium exhibited strong immunostaining
      with mAb HE1/11F, however, the limbal epithelial cells stained weakly. HE1/11F
      recognized 160-kDa (HEBM1) and 100-kDa (HEBM2) polypeptides in the corneal
      epithelial extracts. The amino acid sequence of the protein deduced from the
      nucleotide sequence of the cDNA exhibited a close homology to that of a RhoA (Ras
      related small GTPase)-associated serine-threonine kinase (ROCK-I or Rho
      associated coiled-coil kinase). A 160-kDa RhoA-binding polypeptide with a
      molecular mass similar to that of HEBM1 and ROCK-I was detected in the corneal
      epithelial extracts. These findings strongly suggested that HEBM1 was rabbit ROCK
      I. The identity of HEBM1 was further confirmed from the reactivity of mAb HE1/11F
      with ROCK-I immunoprecipitated from rabbit corneal epithelial extracts using anti
      ROCK-I antibodies. CONCLUSIONS: The increased expression of a protein identified
      as ROCK-I from cDNA analyses is associated with rabbit corneal epithelial
      differentiation and transition from the limbal to corneal surface. Therefore, a
      RhoA signaling pathway is likely to be associated with corneal epithelial
      differentiation (maturation). A close homology among the cDNA sequences of
      rabbit, mouse, rat, and human ROCK-I indicates that this RhoA-associated kinase
      is a well-conserved protein.

PMID- 9620090
TI  - Expression of nerve growth factor receptors on the ocular surface in healthy
      subjects and during manifestation of inflammatory diseases.
AB  - PURPOSE: Recent studies have suggested the involvement of nerve growth factor
      (NGF) in the conjunctival inflammatory process and in corneal epithelium
      proliferation and differentiation. To verify the hypothesis that NGF could
      locally modulate the inflammatory and reparative processes, the authors evaluated
      the expression of NGF high-affinity receptor on the ocular surface in normal and
      pathologic conditions. METHODS: Ten conjunctival biopsies (obtained from three
      healthy subjects, five patients affected by vernal keratoconjunctivitis [VKC],
      and two patients with cicatricial pemphigoid [CP]) and five corneal specimens
      obtained from the Eye Bank of Veneto (Italy) were evaluated. All specimens were
      histologically stained, and immunohistochemistry was performed to identify the
      NGF high-affinity receptor (TrkA). RESULTS: All tissues expressed
      immunoreactivity for NGF receptors. In conjunctival specimens of healthy
      subjects, basal epithelial cells strongly expressed immunoreactivity and, in the
      stroma, rare cells were immunopositive for TrkA. No significant difference in
      immunoreactivity was observed in the conjunctival epithelium between healthy
      subjects and patients with inflammatory conjunctival diseases, whereas there were
      more immunopositive cells observed in the conjunctival stroma of VKC and CP
      patients than in the controls. The immunoreactivity in the cornea was confined to
      basal epithelial cells and endothelium. CONCLUSIONS: The NGF receptor is present
      on the human ocular surface. The authors' data support the possibility that NGF
      modulates ocular inflammation and corneal epithelial proliferation and
      differentiation through its receptors.

PMID- 9620091
TI  - Prenylation of proteins by the intact lens.
AB  - PURPOSE: To describe and identify proteins prenylated by the intact rat lens.
      METHODS: Lenses from young rats were incubated for 24 hours in TC199 medium
      containing 22 microM lovastatin and 110 microCi/ml [3H]mevalonolactone. Proteins
      of the epithelium and fiber cells were separated by high-performance liquid
      chromatography (HPLC) and one- and two-dimensional electrophoresis, and the 3H
      label was detected by fluorography. Treatment of labeled proteins with methyl
      iodide released isoprenes that were identified by HPLC analysis. The identity of
      the prenylated proteins was probed by N-terminal sequence analysis and matrix
      assisted, laser desorption ionization-mass spectrometry (MALDI-MS). RESULTS: The
      pattern of protein prenylation by epithelial and fiber cells was similar. Most of
      the labeled proteins were water insoluble and were assumed to be membrane
      associated. A group of 21-kDa to 29-kDa proteins were most intensely labeled and
      were modified mainly with geranylgeranyl. A highly labeled, approximately 80-kDa
      insoluble protein and a lesser labeled, 64-kDa soluble protein were the only
      other significant prenylated proteins. Both were farnesylated. MALDI-MS analysis
      suggested that the 80-kDa protein is a cytokeratin. N-terminal sequence analysis
      indicated that the 64-kDa soluble protein is beta-tubulin. CONCLUSIONS: A limited
      set of proteins are prenylated by the young rat lens. The 21-kDa to 29-kDa
      proteins were modified mainly by geranylgeranyl and are likely members of the
      numerous small GTP binding proteins. The authors express caution about accepting
      the identities of the 64-kDa and 80-kDa proteins as beta-tubulin and cytokeratin
      1, respectively--proteins in these families do not contain the required CAAX
      motif. The 80-kDa farnesylated protein could be novel and unique to the lens,
      because no farnesylated protein of this size has been previously reported.

PMID- 9620092
TI  - A distinct membrane current in rat lens fiber cells isolated under calcium-free
      conditions.
AB  - PURPOSE: To investigate whether lens fiber cells isolated and maintained under
      calcium-free conditions exhibit distinct membrane currents. METHODS: Fiber cells
      were isolated from the cortical portion of neonate rat lenses using a trypsin
      digestion protocol and were maintained in EDTA-buffered Ringer's solutions.
      Membrane currents were recorded from fiber bundles using the whole-cell patch
      clamp technique. RESULTS: Cortical fiber cells of up to 600-microm length were
      viable and amenable to whole-cell patch-clamp recording. The major current
      recorded under these conditions was a slowly activating, voltage-dependent
      current that was markedly increased on membrane depolarization. This current
      appeared to be fiber cell specific and had similar properties to currents
      elicited by gap junction hemichannels previously recorded by others in Xenopus
      oocytes. CONCLUSIONS: This is the first report of whole-cell patch-clamp
      recordings from intact elongated fiber cells. Fiber cells kept in calcium-free
      bath medium appear to be electrically "leaky" and exhibit a distinct membrane
      current that has not been described previously for lens cells. This current is
      unlikely to be active in the normal lens but may play a role in the depolarized
      cataractogenic lens.

PMID- 9620093
TI  - Binding properties of indocyanine green in human blood.
AB  - PURPOSE: Binding properties of indocyanine green (ICG) to human plasma proteins
      were identified using electrophoresis and a fundus video system. METHODS: Blood
      samples were obtained from three healthy volunteers after intravenous
      administration of ICG. The resulting plasma samples were fractionated by agarose
      gel immunoelectrophoresis and polyacrylamide gel DISC electrophoresis. In the
      former, antisera, anti-apolipoprotein (Apo)-A, and anti-Apo-B antibodies were
      used to identify all classes of plasma proteins, high-density lipoprotein (HDL),
      and low-density lipoprotein (LDL), respectively. In the latter method, plasma
      samples could be separated into chylomicron, very low-density lipoprotein, LDL,
      and HDL. The electrophoretic pattern obtained by each method was observed with an
      ICG fundus video system. Furthermore, we studied the affinity of ICG for lipids
      that were common molecular components of HDL and LDL. Four kinds of ICG solutions
      mixed with phospholipid, free cholesterol, esterified cholesterol, and
      triacylglycerol were observed with the ICG fundus video system. RESULTS: Both
      electrophoretic studies showed that ICG bound intensely to HDL and moderately to
      LDL, and only the solution with phospholipid fluoresced brightly when observed
      with the ICG fundus video system. CONCLUSIONS: These findings indicated low
      vascular or tissue permeability of ICG, which is caused by the larger molecular
      size of HDL and LDL. Also noted was that the ICG fluorescence observed in the
      angiogram may be equivalent to the hemodynamics of HDL alone or in combination
      with LDL in the bloodstream. This biochemical consideration may be a basis for
      the further understanding of ICG angiography.

PMID- 9620094
TI  - The organophosphate pesticide chlorpyrifos affects form deprivation myopia.
AB  - PURPOSE: The effects of the anti-cholinesterase organophosphate pesticide
      chlorpyrifos (CPF) on the refractive development of the eye were examined. Form
      deprivation was used to induce eye growth to address the previously reported
      relationship between organophosphate pesticide use and the incidence of myopia.
      METHODS: Chickens, a well-established animal model for experimental myopia and
      organophosphate neurotoxicity, were dosed with chlorpyrifos (3 mg/kg per day,
      orally, from day 2 to day 9 after hatching) or corn oil vehicle (VEH) with or
      without monocular form deprivation (MFD) over the same period. The set of
      dependent measures included the refractive state of each eye measured using
      retinoscopy, axial dimensions determined with A-scan ultrasound, and intraocular
      pressure. RESULTS: Dosing with CPF yielded an inhibition of 35%
      butyrylcholinesterase in plasma and 45% acetylcholinesterase in brain. MFD
      resulted in a significant degree of myopia in form-deprived eyes resulting from
      significant lengthening of the vitreal chamber of the eye. CPF significantly
      reduced the effect of MFD, resulting in less myopic eyes (mean refraction: VEH
      MFD = -16.2 +/- 2.3 diopters; CPF-MFD = -11.1 +/- 1.8 diopters) with
      significantly shorter vitreal chambers. Nonoccluded eyes were, on average,
      slightly hyperopic. Treatment with CPF for 1 week in the absence of MFD led to no
      significant change in ocular dimensions or refraction relative to controls.
      CONCLUSIONS: The use of form deprivation as a challenge suggests that CPF
      treatment interferes with the visual regulation of eye growth.

PMID- 9620095
TI  - Understanding retinal cytosolic reductive stress.

PMID- 9620096
TI  - Controversies in antithrombotic therapy for patients with mechanical heart
      valves.
AB  - Current anticoagulation guidelines for patients with mechanical heart valves are
      based on studies that are seriously flawed in that they used prothrombin time
      ratios rather than the international normalized ratio (INR) and failed to
      consider the level of anticoagulation actually achieved. Available data suggest
      that the appropriate INR range varies according to risk factors and that "tight
      control" of the INR is of critical importance in reducing thromboembolic and
      hemorrhagic events. Whether antiplatelet therapy adds benefit to an appropriately
      controlled level of anticoagulation is not clear. During pregnancy, warfarin is
      contraindicated; adjusted-dose heparin is recommended by published American and
      European guidelines. Even so, one small study suggests that this may be
      inadequate. Topical antifibrinolytic agents can negate the need to alter systemic
      anticoagulation during dental surgery.

PMID- 9620097
TI  - The pharmacologic and bacteriologic properties of oxazolidinones, a new class of
      synthetic antimicrobials.
AB  - The oxazolidinones are a new synthetic class of antimicrobials structurally
      unrelated to any agent presently marketed. Data pertaining to these compounds,
      with respect to their pharmacology, pharmacokinetics, pharmacodynamics, mechanism
      of action, and bacteriologic activity, focusing on the analogs linezolid (PNU
      100766) and eperezolid (PNU 100592), were retrieved by MEDLINE search and review
      of relevant abstracts presented at recent clinical conferences. Since the drugs
      are still investigational, we obtained in vitro and animal data as well as
      available human studies. The oxazolidinones have bacteriostatic activity against
      a number of important pathogens including methicillin-resistant Staphylococcus
      aureus, penicillin-resistant Streptococcus pneumoniae, and vancomycin-resistant
      enterococci. They appear to be efficacious and well tolerated both orally and
      parenterally. Their role remains to be elucidated by clinical trials.

PMID- 9620098
TI  - Mibefradil, a pharmacologically distinct calcium antagonist.
AB  - Mibefradil is the prototype of a new class of calcium antagonists that
      selectively block T-type voltage-gated plasma membrane calcium channels in
      vascular smooth muscle. The drug is structurally and pharmacologically different
      from traditional calcium antagonists. It does not have negative inotropism at
      therapeutic concentrations, and is not associated with reflex activation of
      neurohormonal and sympathetic systems. In clinical studies of hypertension,
      mibefradil 50 and 100 mg/day reduced trough sitting diastolic and systolic blood
      pressures in a dose-related manner. Dosages exceeding 100 mg/day generally did
      not result in significantly greater efficacy, but were associated with a higher
      frequency of adverse events. No first-dose hypotensive phenomenon was observed.
      Mibefradil has antiischemic properties resulting from dilation of coronary and
      peripheral vascular smooth muscle, and a slight reduction in heart rate. In
      clinical studies of chronic stable angina pectoris, dose-related increases in
      exercise duration, time to onset of angina, and time to 1-mm ST-segment
      depression during exercise tolerance tests occurred. Mibefradil reduced the
      number and duration of ischemic events recorded by 48-hour ambulatory
      electrocardiograph (ECG) monitoring, as well as number of anginal episodes and
      nitroglycerin consumption. Favorable hemodynamic and clinical profiles are
      reported, including high trough:peak ratios (> 80%), high oral bioavailability,
      and long elimination half-life (17-25 hrs) permitting once/day dosing. Dizziness,
      headache, leg edema, and lightheadedness are frequently reported, but overall the
      agent is well tolerated. First-degree atrioventricular block and sinus
      bradycardia are the most frequent ECG changes caused by the drug. In vitro
      studies indicate mibefradil inhibits cytochrome P450 1A2, 2D6, and 3A4, resulting
      in elevated plasma concentrations of drugs metabolized by those isoenzymes.
      Therefore, it is contraindicated in patients receiving terfenadine, astemizole,
      cisapride, lovastatin, or simvastatin.

PMID- 9620099
TI  - Gastric colonization as a consequence of stress ulcer prophylaxis: a prospective,
      randomized trial.
AB  - STUDY OBJECTIVE: To evaluate gastric alkalization and bacterial colonization in
      critically ill patients receiving stress ulcer prophylaxis with gastric tube
      feeds, sucralfate, intermittent intravenous cimetidine, or continuous intravenous
      cimetidine. DESIGN; Prospective, randomized, unblinded trial. SETTING: Medical
      and surgical intensive care units of a large university-affiliated, tertiary care
      community hospital. PATIENTS: Fifty-three evaluable critically ill patients with
      respiratory failure requiring mechanical ventilation. INTERVENTIONS: Patients not
      receiving nasogastric tube feeds were randomized to sucralfate 1 g every 6 hours,
      cimetidine 300 mg by intravenous bolus every 8 hours, or cimetidine 900 mg by
      continuous intravenous infusion/24 hours. Gastric samples were obtained daily for
      pH and culture. MEASUREMENTS AND MAIN RESULTS: Patients with respiratory failure
      and a high mortality rate had a mean gastric pH of 1.96 +/- 1.5 at study entry.
      There were no significant differences in gastric pH or gastric colonization among
      the three arms. Fourteen patients (26%) developed gastric colonization, which was
      statistically significant but poorly correlated with gastric alkalinity (r2=0.08,
      p<0.043). CONCLUSION: Gastric luminal pH was unchanged regardless of which method
      was used for stress ulcer prophylaxis. Bacterial colonization was increasingly
      likely in patients with a persistent alkaline gastric environment.

PMID- 9620100
TI  - The effect of food on bromfenac, naproxen sodium, and acetaminophen in
      postoperative pain after orthopedic surgery.
AB  - STUDY OBJECTIVES: To evaluate the effect of a standard meal on bioavailability of
      bromfenac, and on the relative analgesic efficacy and adverse effect liability of
      bromfenac 25 mg, naproxen sodium 550 mg, and acetaminophen 325 mg in the
      treatment of pain after orthopedic surgery. DESIGN: Randomized, double-blind,
      single-dose, parallel-group. SETTING: Two wards of the orthopedic surgery
      department at the Central Hospital, Karlstad, Sweden. PATIENTS: Three hundred ten
      patients with steady, moderate, or severe pain within 72 hours after orthopedic
      surgery. INTERVENTIONS: Patients were randomly assigned both to receive a
      standard meal or remain in a fasted state, and to treatment with a single oral
      dose of bromfenac 25 mg, naproxen sodium 550 mg, or acetaminophen 325 mg, when
      they experienced steady, moderate, or severe pain that required an analgesic.
      Using a self-rating record, subjects rated their pain and its relief for up to 8
      hours after medicating. Blood samples were obtained from all patients using one
      of two schedules. MEASUREMENTS AND MAIN RESULTS: The peak plasma bromfenac
      concentration for fed patients was only 28% of that of fasted patients.
      Disregarding food intake, bromfenac 25 mg and naproxen sodium 550 mg were
      significantly superior to acetaminophen 325 mg for all summary measures of
      analgesia. Bromfenac and naproxen were superior to acetaminophen by hour 1 and
      this difference persisted for 8 hours. Food reduced bromfenac's analgesic effect,
      but not that of naproxen or acetaminophen; treatment by meal interaction was
      significant for five measures of efficacy. Analgesic response for fed bromfenac
      recipients, compared with those who were fasted, ranged from 37-71%. The
      percentage of patients reporting an adverse effect was significantly higher for
      bromfenac (25%) and naproxen (24%) than for acetaminophen (12%). CONCLUSIONS:
      Results of analgesic studies not taking patients' food status into consideration
      might be misleading. Although bromfenac 25 mg and naproxen sodium 550 mg produced
      significant analgesia compared with acetaminophen 325 mg, bromfenac's efficacy
      was significantly reduced when patients ate a standard meal. Adverse effects were
      transient and consistent with the pharmacologic profiles of the drugs.

PMID- 9620101
TI  - A double-blind study comparing two single-dose regimens of ketorolac with
      diclofenac in pain due to cancer.
AB  - STUDY OBJECTIVE: To compare the analgesic efficacy and safety of two single doses
      of ketorolac with diclofenac in acute cancer pain. DESIGN: Double-blind,
      randomized, clinical study. SETTING: Hospital-based clinical research center.
      SUBJECTS: One hundred eighty patients suffering acute, moderate, or severe cancer
      pain. INTERVENTIONS: A single intramuscular injection of ketorolac 10 or 30 mg or
      diclofenac 75 mg. MEASUREMENTS AND MAIN RESULTS: Pain intensity was assessed 30
      minutes and 1, 2, 3, 4, 5, and 6 hours after injection or until rescue drug
      administration. In approximately 70% of patients all treatments provided prompt
      sustained pain relief throughout the 6-hour observation period. There were no
      statistically significant differences in any of the analyzed efficacy measures
      among the three groups. CONCLUSION: Intramuscular ketorolac 10 mg is adequate to
      relieve cancer pain, and is equivalent to ketorolac 30 mg and to diclofenac 75
      mg.

PMID- 9620102
TI  - Update on clinical antifungal susceptibility testing for Candida species.
AB  - With the emergence of fungi as important nosocomial pathogens, increasing reports
      of antifungal resistance, and expanding drug therapy options, the need for
      clinically relevant antifungal susceptibility testing is evident. Over the last
      decade, the National Committee for Clinical Laboratory Standards (NCCLS) worked
      to standardize procedures for in vitro susceptibility testing of Candida species
      against fluconazole, itraconazole, 5-fluorocytosine, and amphotericin B. With the
      establishment of a reproducible methodology, correlation of antifungal
      susceptibility in vitro with clinical outcome is a priority. The NCCLS proposed
      susceptibility breakpoints for the three agents against Candida species, with
      breakpoints for amphotericin B forthcoming. These breakpoints could provide
      useful guidance in some clinical situations involving azole or 5-fluorocytosine
      therapy; however, routine susceptibility testing of fungal isolates should be
      discouraged.

PMID- 9620103
TI  - Drug and defibrillator interactions.
AB  - We reviewed the interactions of drugs and defibrillators, with emphasis on
      implantable cardioverter defibrillators. Articles were identified by searching
      MEDLINE from 1966 to the present; additional sources were identified from
      reference lists in these articles. Drugs have the potential for both beneficial
      and harmful interactions with electrical therapy. Beneficial interactions include
      reductions in the energy required to defibrillate the heart and in the occurrence
      of arrhythmia resulting in decreased shock frequency, prolonged device longevity,
      and improved patient comfort. Potentially harmful interactions include altering
      the detection of ventricular tachycardia; altering the pacing threshold,
      resulting in interference with bradycardia or antitachycardia pacing; development
      of incessant ventricular tachycardia; and increasing the energy required to
      defibrillate the heart. As the use of implantable cardioverter defibrillators
      increases, pharmacists should be aware of the potential for drug-device
      interactions.

PMID- 9620104
TI  - Insulin lispro, a new insulin analog.
AB  - Insulin lispro is a rapid-acting insulin analog to regular insulin. Inversion of
      the proline-lysine amino acid sequence at positions 28 and 29 on the B chain is
      responsible for its more rapid absorption, faster onset, and shorter duration of
      action compared with regular insulin. The fast onset of action allows for greater
      flexibility in dosing and mealtime scheduling. Insulin lispro provides equivalent
      or slightly improved glycemic control in patients with types I and II diabetes
      mellitus compared with regular insulin, without subsequent increases in
      hypoglycemic episodes. It also results in greater reduction in postprandial blood
      glucose excursion than regular insulin. Compared with other insulins, insulin
      lispro represents a more physiologic approach to exogenous insulin therapy.

PMID- 9620105
TI  - Troglitazone in type II diabetes mellitus.
AB  - Troglitazone, a new antihyperglycemic agent, is approved for use alone, with oral
      sulfonylureas, or with insulin in the treatment of type II diabetes mellitus.
      Rather than stimulating insulin secretion, it enhances insulin sensitivity.
      Potential advantages of troglitazone over oral sulfonylureas include decreased
      endogenous insulin concentrations, decreased exogenous insulin requirements,
      reduced hypoglycemic risk, and convenient once/day administration. The effect on
      morbidity and mortality from lowering endogenous and exogenous insulin
      concentrations remains to be determined. Troglitazone also has potential
      disadvantages. It induces cytochrome P450 isoenzyme 3A4, although few drug
      interactions have been identified to date. Serum transaminases must be monitored
      routinely because of rarely reported cases of idiosyncratic hepatocellular
      injury. In addition, the cost of troglitazone is much higher than that of other
      oral antihyperglycemic agents or insulin. Given the available information,
      troglitazone has limited benefit over oral sulfonylureas or metformin as
      monotherapy or in combination with oral sulfonylureas. Until additional
      combination and comparative studies have been done, the agent should be reserved
      for patients with poor glycemic control receiving high daily doses of insulin.

PMID- 9620106
TI  - Antifungal prophylaxis to prevent invasive mycoses among bone marrow
      transplantation recipients.
AB  - We reviewed the effect of systemic, intranasal, and lipid formulations of
      amphotericin B, fluconazole, itraconazole for antifungal prophylaxis.
      Specifically we reviewed the effect of antifungal prophylaxis on the development
      of fungal colonization, frequency of superficial and invasive mycosis, and
      overall mortality and that due to invasive mycoses in bone marrow transplantation
      recipients. A MEDLINE search was conducted to identify literature describing the
      risk factors, epidemiology, and chemoprophylaxis of invasive mycosis in these
      patients. Preliminary data published as abstracts at national infectious diseases
      and hematology conferences within the last 5 years were included. Antifungal
      prophylaxis reduces fungal colonization and superficial infection. The ability of
      antifungal prophylaxis to prevent systemic infection or reduce the need for
      empiric amphotericin B depends on specific variables. Ultimately, antifungal
      prophylaxis has no affect on overall mortality, and very little impact on
      mortality attributed to fungi.

PMID- 9620107
TI  - Treatment of septic shock with immunotherapy.
AB  - Sepsis is the thirteenth leading cause of death in the United States. Despite
      increased knowledge about its pathophysiology, availability of powerful
      antibiotics, and advanced diagnostic and monitoring techniques, mortality rates
      have not changed significantly over the past 30 years. Immunotherapy may improve
      outcome in the critically ill with sepsis, although trial results have been
      disappointing to date.

PMID- 9620108
TI  - Ketoconazole in the prevention of acute respiratory distress syndrome.
AB  - We conducted a critical review of the literature on ketoconazole in preventing
      acute respiratory distress syndrome (ARDS), a serious disorder associated with
      high mortality. Two double-blind, prospective, placebo-controlled, randomized
      trials compared ketoconazole with placebo for prophylaxis of ARDS. In one trial,
      compared with placebo, ketoconazole resulted in a reduced frequency of ARDS (6%
      vs 31%, p<0.01), lower plasma thromboxane B2 levels (33 vs 75 pg/ml, p<0.05), and
      shorter intensive care unit stay (7 vs 15.5 days, p<0.05). In the second trial
      the drug reduced the frequency of ARDS (15% vs 64%, p=0.002), lowered thromboxane
      B2 levels (83 vs 143 pg/ml), and reduced mortality (15% vs 39%, p=0.05) compared
      with placebo. Larger multicenter studies are warranted to validate the findings
      of these two trials.

PMID- 9620109
TI  - Pharmacologic, pharmacokinetic, and therapeutic differences among ACE inhibitors.
AB  - Angiotensin-converting enzyme (ACE) inhibitors are a heterogeneous group of
      agents, and important pharmacologic, pharmacokinetic, and therapeutic differences
      among them must be understood to obtain optimal therapy. For patients with severe
      liver disease, lisinopril and captopril are not prodrugs (e.g., do not require
      hepatic activation), and lisinopril has almost solely renal elimination.
      Enalaprilat, the intravenous formulation of enalapril, is the only intravenously
      available ACE inhibitor and can be given to patients with severe liver
      dysfunction as it is also not a prodrug. Fosinopril is the only drug with
      compensatory dual routes of elimination, and it does not require dosage
      adjustment in patients with reduced renal function, as other ACE inhibitors do.
      Captopril and moexipril have potential drug-food interactions and are the only
      agents that should be spaced from meals. The ACE inhibitors also differ in their
      dialyzability, half-life, lipophilicity, trough:peak ratios, approved
      indications, and therapeutic information available for many indications.

PMID- 9620110
TI  - A review of anticonvulsants in treating agitated demented elderly patients.
AB  - Agitation in the elderly, manifested by verbal and physical aggression,
      frequently results in increased morbidity and mortality for nursing home
      residents and reduced morale for the family and nursing home staff. It is also
      responsible for increased costs associated with caring for these residents.
      Pharmacologic interventions are often used but are frequently ineffective and
      associated with significant adverse effects. Few controlled studies of drug
      treatment are available, but divalproex sodium and carbamazepine are effective
      and well tolerated by this population. Divalproex sodium has advantages of fewer
      adverse side effects and drug-drug interactions.

PMID- 9620111
TI  - The risk of seizures associated with tramadol.
AB  - We conducted a study of the risk of idiopathic incident seizures among users of
      tramadol derived from data present in the General Practice Research Database
      based in the United Kingdom for 1994-1996. We used a nested case-control study
      design, comparing risks of idiopathic incident seizures during exposed and
      unexposed times among patients who had ever taken tramadol using a 90-day follow
      up. Among the 10,916 subjects, we identified 17 cases of idiopathic seizures, 11
      of which were definite and 6 possible. None of the patients was exposed to
      tramadol alone in the prior 90 days. Eight patients were exposed to opiates, five
      to both tramadol and opiates, three to other analgesics, and one to no
      analgesics. We found no increased risk of idiopathic incident seizures associated
      with exposure to tramadol alone. Thus seizures seem rarely attributable to the
      agent.

PMID- 9620112
TI  - Nitric oxide concentrations and cerebrospinal fluid parameters in an experimental
      animal model of Streptococcus pneumoniae meningitis.
AB  - Streptococcus pneumoniae is a common cause of meningitis. Nitric oxide (NO) has
      been implicated in causing cerebral edema. Modulating NO production in
      cerebrospinal fluid (CSF) may have a role in the treatment of bacterial
      meningitis. Experimental S. pneumoniae meningitis was induced in a rabbit model
      to determine CSF parameters and NO concentrations. An electrochemical probe in
      the CSF throughout the 7-hour experiment monitored NO concentrations. The animals
      had S. pneumoniae (10(5)) injected intracisternally and incubated for 1 hour.
      Cerebrospinal fluid 200-300 microl was obtained by intracisternal puncture at
      zero, 2, 4, and 7 hours after drug administration to measure glucose, protein,
      and lactic acid by standard chemical methods. White blood cell count was measured
      by hemocytometry. Three groups of five animals were used-control (C), ceftriaxone
      (CTX), and ceftriaxone plus dexamethasone (CTX+D). Ceftriaxone concentrations in
      CSF were obtained by microdialysis and analyzed by high-performance liquid
      chromatography. Mean (+/- SEM) CSF white blood cell count was significantly
      higher at 2 hours in the C group than in the other two groups (C 7307 +/- 1302,
      CTX 605 +/- 345, CTX+D 730 +/- 43/mm3, p<0.002). Ceftriaxone induced a
      significant rise in protein at 4 hours compared with the other groups (C 364 +/-
      107, CTX 1158 +/- 797, CTX+D 365 +/- 100 mg/dl, p<0.02). Cerebrospinal fluid
      lactic acid was significantly different at 4 and 7 hours between C and CTX+D
      groups (4-hr C 8.0 +/- 2.2, CTX+D 2.0 +/- 0.4 mmol/L, p<0.05; 7-hr C 10.2 +/-
      2.4, CTX+D 2.8 +/- 0.8 mmol/L, p<0.01). Median NO concentrations were
      significantly elevated in the control group compared with the other two groups (C
      11.7, CTX 6.8, CTX+D 6.5 micro, p<0.02 C vs CTX, p<0.01 C vs CTX+D). Average (+/-
      SEM) NO concentrations were significantly higher in the C group at 4 hours (18.1
      +/- 0.4, CTX 5.8 +/- 1.8 microM, p<0.05; CTX+D 11.5 +/- 4.0 microM, p>0.05),
      whereas they did not rise significantly until 7 hours in the CTX group (CTX 18.7
      +/- 0.7, C 8.9 +/- 0.4 microM, p=0.055; CTX+D 8.1 +/- 2.2 microM, p<0.05). These
      results indicate that ceftriaxone with or without dexamethasone significantly
      decreases lactic acid concentrations and white cell penetration into the CSF in
      an experimental model of S. pneumoniae meningitis. In addition, ceftriaxone
      induced a significant elevation in CSF protein. Median NO production in the CSF
      was significantly attenuated by ceftriaxone.

PMID- 9620113
TI  - Caucasian versus African-American differences in orosomucoid: potential
      implications for therapy.
AB  - We conducted a prospective, nonrandomized study in healthy volunteers to
      determine if racial differences exist in orosomucoid (ORM) and its variants, and
      to examine quinidine and lidocaine binding to the protein. Total ORM serum
      concentrations were measured by Laurell-Rocket immunoelectrophoresis. Allele
      types were determined by isoelectric focusing and immunoblotting. Total and
      unbound quinidine and lidocaine concentrations were measured with standard
      fluorescence polarization immunoassays after ultrafiltration. The frequency of
      the common ORM alleles was similar between 38 Caucasians and 67 African
      Americans. Mean total ORM concentration was significantly lower in Caucasians
      (57.3 +/- 25.4 vs 73.2 +/- 33.9 mg/dl, p=0.01). However, more Caucasians took
      oral contraceptives, which may have decreased ORM concentrations. Quinidine
      unbound fraction (UF) was related to ORM phenotype. The highest UF was found with
      ORM 1-S (p=0.009). There were no significant relationships between ORM phenotype
      and lidocaine UF. Overall, African-Americans had higher ORM concentrations than
      Caucasians. Quinidine binding showed significant relationships to specific ORM
      variants.

PMID- 9620114
TI  - Potential angiotensin-converting enzyme inhibitor-epoetin alfa interaction in
      patients receiving chronic hemodialysis.
AB  - We compared epoetin alfa (EPO) dose requirements and hematocrit response in 17
      patients receiving chronic hemodialysis at baseline and after 3 and 12 months of
      therapy with angiotensin-converting enzyme (ACE) inhibitors (12 enalapril, 5
      captopril). No acute processes were present (infection, hemorrhage, inflammation)
      at time of starting ACE inhibitor therapy. Mean (+/- SD) intravenous EPO dosages
      at zero, 3, and 12 months were 6012 +/- 2575, 5800 +/- 2026, and 5660 +/- 2285 U
      3 times/week (p=0.56), and mean differences were -212 U for 0-3 months (95% CI 
      1310 to 886) and -713 U for 0-12 months (95% CI -2142 to 716). Mean +/- SD
      hematocrits were 30.5 +/- 3.9%, 31.6 +/- 3.2%, and 34.2 +/- 3.1% (p=0.01, zero vs
      12 mo), and mean differences were 1.7% for 0-3 months (95% CI -1.41 to 4.81) and
      3.85% for zero-12 months (95% CI 0.71-7). Our results indicate that ACE
      inhibitors do not increase EPO dose requirements or reduce hematocrits in these
      patients.

PMID- 9620115
TI  - Influenza vaccination and warfarin anticoagulation: a comparison of subcutaneous
      and intramuscular routes of administration in elderly men.
AB  - STUDY OBJECTIVES: To determine if subcutaneous administration of influenza
      vaccine is as immunogenic as the intramuscular route, and to evaluate the
      frequency of local adverse events associated with both routes in elderly
      anticoagulated men. DESIGN: Single-blind, prospective study of consecutively
      enrolled subjects. SETTING: Ambulatory clinic at a university-affiliated Veterans
      Affairs medical center. PATIENTS: Twenty-six men age 60 years or older, receiving
      therapeutic dosages of warfarin. INTERVENTIONS: Subjects were randomized to
      receive either intramuscular or subcutaneous injection of a standard trivalent
      influenza vaccine. MEASUREMENTS AND MAIN RESULTS: Serum antibody titers to the
      vaccine's components were measured at baseline, and 6 weeks and 4 months after
      vaccination. Both routes of administration induced comparable serum antibody
      titers. There were no differences in adverse events at administration sites
      between routes of administration. CONCLUSIONS: Elderly individuals are able to
      mount an immune response to influenza vaccine and produce antibody concentrations
      deemed protective. The routes of administration are similarly effective at
      inducing an immune response. The intramuscular route in anticoagulated elderly
      men does not commonly result in local bleeding complications.

PMID- 9620116
TI  - Bioavailability of phenytoin acid and phenytoin sodium with enteral feedings.
AB  - STUDY OBJECTIVE: To compare the absolute bioavailability of phenytoin (PHT)
      sodium solution and PHT acid suspension in healthy volunteers receiving
      continuously infused enteral feedings. DESIGN: Randomized, open-label, single
      dose, three-period crossover study. SETTING: University clinical research center.
      SUBJECTS: Ten healthy volunteers age 23-43 years. INTERVENTIONS: The three phases
      of the study were separated by at least 7 days. During phase A, subjects received
      PHT sodium 435 mg intravenously over 30 minutes. During phases B and C, subjects
      had a nasogastric feeding tube placed through which PHT acid suspension 400 mg
      and PHT sodium solution 435 mg were administered, respectively. For phases B and
      C, continuous enteral feedings were given by feeding tube for 14 hours before and
      after the PHT dose. Blood samples were collected over 72 hours after each PHT
      dose, and the serum was analyzed for PHT. MEASUREMENTS AND MAIN RESULTS: The rate
      and extent of PHT absorption and PHT pharmacokinetics were determined using an
      empirical quadratic function of time method. Bioavailability, rate of absorption,
      maximum concentration (Cmax), and time to maximum concentration (Tmax) were
      compared for the two enteral doses by paired Student's t test. There were no
      significant differences in bioavailability for PHT acid suspension and PHT sodium
      solution (0.88 +/- 0.15 vs 0.91 +/- 0.7, p=0.57, 90% CI -0.14-0.071). The Cmax
      was greater (7.4 +/- 0.9 mg/L vs 5.5 +/- 1.7 mg/L, p=0.019) and Tmax was less
      (2.5 +/- 3.8 vs.14.8 +/- 11.2 hrs, p=0.004) for the sodium solution. The time to
      50% fractional absorption (0.33 +/- 0.08 vs 3.2 +/- 2.4 hrs, p=0.004) and 90%
      fractional absorption (7.9 +/- 6.2 vs 22.3 +/- 17.2 hrs, p=0.021) was also
      significantly shorter for the sodium solution. CONCLUSION: The absolute
      bioavailability of the two dosage forms of PHT administered with concomitant
      enteral feedings were not significantly different, however, the absorption
      patterns were significantly different, with the sodium solution being more
      rapidly absorbed.

PMID- 9620117
TI  - Warfarin resistance in a patient with short bowel syndrome.
AB  - Drug therapy in short bowel syndrome can be complicated by inadequate or
      incomplete absorption of drugs in the small intestine. Many case reports claim
      that warfarin absorption is not affected by the syndrome. We treated a patient
      with oral warfarin for recurring deep vein thrombosis; up to 20 mg/day was
      administered with no increase in the international normalized ratio. Drug-drug
      interactions that may prevent absorption, increase metabolism, or antagonize the
      effects of warfarin were ruled out. Intravenous lipid administration, which is
      anecdotally reported to precipitate warfarin resistance, may have contributed to
      the condition, but dosing was less frequent than in published reports. The most
      probable explanation of warfarin resistance is the reduced surface area for drug
      absorption secondary to surgical removal of the patient's duodenum and
      gastrojejunostomy.

PMID- 9620118
TI  - Failure of once-daily vancomycin for staphylococcal endocarditis.
AB  - With the emergence of staphylococci as important hospital pathogens,
      administration of vancomycin has increased dramatically. Economic and other
      factors have led to the development of once-daily dosing protocols to simplify
      and standardize the administration of antibiotics. A patient with Staphylococcus
      aureus prosthetic valve endocarditis and normal renal function failed therapy
      with vancomycin once/day. The infection was cured when the regimen was changed to
      the conventional 12-hour dosing interval.

PMID- 9620119
TI  - Elevated pancreatic enzymes after extended propofol therapy.
AB  - Propofol is a sedative hypnotic agent often administered for intensive care
      sedation. A 28-year-old man who suffered a severe head injury developed elevated
      pancreatic enzymes after receiving extended high-dosage propofol therapy. Amylase
      and lipase values gradually reduced toward normal after the drug was
      discontinued. Possible propofol-induced pancreatitis was reported with short-term
      but not with prolonged therapy. A definitive cause-and-effect relationship is
      unclear since head trauma also was reported to cause elevated pancreatic enzymes.
      Intensive care practitioners should be aware of this potential reaction.

PMID- 9620120
TI  - Acute renal failure, anterior myocardial infarction, and atrial fibrillation
      complicating epinephrine abuse.
AB  - After injecting the solution extracted from a Primatene Mist inhaler, a patient
      experienced epinephrine overdose that resulted in an acute myocardial infarction
      and acute renal failure. The exact amount of epinephrine injected was unknown,
      but was thought to be between 82.5 and 124 mg, more than 25 times higher than the
      amount normally administered. Health care providers should be aware of this
      readily available source of epinephrine and the potential adverse effects
      associated with its inappropriate use.

PMID- 9620121
TI  - Precipitous fall in platelet count with anagrelide: case report and critique of
      dosing recommendations--a comment.

PMID- 9620122
TI  - Prediction of Listeria spp. growth as affected by various levels of chemicals,
      pH, temperature and storage time in a model broth.
AB  - The effects of concentration of NaCl (0.5 to 12.5%), methyl paraben (0.0 to
      0.2%), sodium propionate (0.3%), sodium benzoate (0.1%), potassium sorbate
      (0.3%), pH (> 5.9) temperature (4 to 30 degrees C), storage time (up to 58 d) and
      inoculum (> 10(5) to > 10(-2) per ml) on the log10 probability percentage of one
      cell of Listeria spp. to initiate growth in a broth system were evaluated in a
      factorial design study. At pH 5.96 and temperature ranging from 4 to 30 degrees C
      the concentrations of sodium propionate, potassium sorbate, and sodium benzoate
      examined allowed growth of L. monocytogenes with lag phases at 4 degrees C of 18,
      27 and 21 days, respectively. For 0.1 and 0.2% methyl paraben growth of all
      Listeria spp. was initiated at 8 degrees C and 30 degrees C, respectively. At pH
      6, concentration of 12% NaCl supported the growth of L. monocytogenes at 8 to 30
      degrees C, whereas 12.5% inhibited all Listeria species. Four regression
      equations were derived relating probability of growth initiation to temperature,
      concentrations of NaCl and preservatives storage time, and Listeria species
      specific effects. From these equations, the number of cells needed for growth
      initiation can be calculated. The impact of this type of quantitative study and
      its possible application on the development of microbial standards for foods is
      discussed.

PMID- 9620123
TI  - The effect of growth temperature on the phospholipid and fatty acyl compositions
      of non-proteolytic Clostridium botulinum.
AB  - A non-proteolytic strain of Clostridium botulinum (NCIB 4270) was found to have a
      complex lipid composition, comprising five major phosphorus-containing lipids:
      phosphatidylethanolamine (PE), phosphatidylglycerol (PG), diphosphatidylglycerol
      (DPG), phosphatidylserine (PS) and a glycophospholipid of unknown structure
      (GPL), in order of abundance. Changing the growth temperature did not alter the
      lipid composition either qualitatively or quantitatively. The main fatty acyl
      components of the lipids are 14:0, 16:0 and 16:1. When the growth temperature was
      lowered from 37 to 8 degrees C, there was an increase in 14:0 from 16.4 to 37.5%,
      an increase in 16:1 from 10.5 to 22.5%, and a decrease in the proportion of 16:0
      from 40.3 to 19.1%. There was also a decrease in the proportion of cyclopropane
      fatty acids (15:0cyc and 17:0cyc) from 7.3 to 0.5%, and in the equivalent chain
      length of the total fatty acids from 15.9 to 15.3 as the temperature was lowered.
      The same temperature-dependent changes occurred in the five major lipid classes
      examined. Despite reports of the presence of plasmalogenic forms of phospholipids
      (i.e. those lipids which have the acyl chain in the sn-1 position replaced by an
      alk-1-enyl group) in some Clostridium spp., none were detected in C. botulinum
      NCIB 4270 using either commercially available spray reagents or by gas-liquid
      chromatographic analysis of the products or acid methanolysis of total lipid
      extracts. It is concluded that non-proteolytic C. botulinum lacks plasmalogens,
      typical of other clostridia, in its membranes and instead modulates its fatty
      acid composition in response to temperature changes in a manner that is typical
      of other (non-clostridial) bacteria.

PMID- 9620124
TI  - Phosphate group requirement for mitogenic activation of lymphocytes by an
      extracellular phosphopolysaccharide from Lactobacillus delbrueckii ssp.
      bulgaricus.
AB  - The mitogenic activity of extracellular polysaccharides produced by Lactobacillus
      delbrueckii ssp. bulgaricus OLL 1073R-1 and NCFB2483 was examined in murine
      lymphocytes. The extracellular polysaccharide from Lactobacillus delbrueckii ssp.
      bulgaricus OLL 1073R-1 was fractionated into neutral and acidic polysaccharides
      by anion-exchange chromatography, while that of Lactobacillus delbrueckii ssp.
      bulgaricus NCFB2483 were all fractionated into neutral polysaccharide(s). The
      acidic polysaccharide stimulated mitogenic responses of murine splenocytes and
      Peyer's patches but not of thymocytes. The optimal concentration of the acidic
      polysaccharide at the highest stimulation was 160 microg/ml. A significant
      increase of mitogenic activity was initiated at 24 h, and the highest response
      was obtained after stimulation for 48 h. The acidic polysaccharide purified by
      high performance liquid chromatography also had substantial mitogenic activity,
      and the molecular weight was estimated to be 1.2 x 10(6). The acidic
      polysaccharide was a phosphopolysaccharide consisting of glucose, galactose and
      phosphorus. Dephosphorylation by hydrofluoric acid degradation reduced the
      mitogenic activity in lymphocytes. The phosphopolysaccharide produced by
      Lactobacillus delbrueckii ssp. bulgaricus 1073R-1 is a potent B-cell-dependent
      mitogen in which the phosphate group acts as a trigger of the mitogenic
      induction.

PMID- 9620125
TI  - Antimicrobial spectrum and target site of D-3-phenyllactic acid.
AB  - Geotrichum candidum excretes D-3-phenyllactic acid, which inhibits the growth of
      Listeria monocytogenes. It was found to inhibit a range of gram-positive bacteria
      found in humans and foodstuffs, such as Staphylococcus aureus and Enterococcus
      faecalis, and gram-negative bacteria from humans, such as Providencia stuartii
      and Klebsiella oxytoca. Scanning electron microscope studies on the effect of D-3
      phenyllactic acid on L. monocytogenes showed that it caused changes in bacterial
      behavior and structure. The bacteria formed aggregates and secreted
      polysaccharides; their cell walls lost their rigidity, causing the cells to
      swell. Finally the bacteria broke down completely and the cells disintegrate.

PMID- 9620126
TI  - Model of the influence of time and mild temperature on Listeria monocytogenes
      nonlinear survival curves.
AB  - Heat treatment has long been regarded as one of the most widely used and most
      effective means of destroying pathogens in food. Up to now the linear
      relationship between the death rate and the temperature has been used when
      choosing the best heat treatment to apply. However, the information given by this
      linear relationship is no longer sufficient when nonlinear survival curves are
      observed. Consequently, the agri-food industry needs a tool to choose the best
      mild heat treatment to apply in the case of nonlinear survival curves. This study
      deals with the temperature-induced death of Listeria monocytogenes CIP 7831 in
      the stationary phase of growth. Eleven temperatures were tested. With the
      proposed primary and secondary models good fits of our data were obtained. A
      model describing both the effect of the duration of treatment and the temperature
      on the logarithm of the number of survivors was then built. A clear increase in
      the precision of the estimation of the parameters was obtained with this model.
      Moreover, with this model a new graphical strategy to choose a mild heat increase
      regarding a maximal survivor number has been proposed.

PMID- 9620127
TI  - Antimicrobial resistance and R-factor transfer of salmonellae isolated from
      chicken carcasses in Greek hospitals.
AB  - A total of 62 salmonellae, belonging to six different serotypes, were isolated
      from 60 out of 87 (69.0%) chicken carcasses delivered to hospitals of
      Thessaloniki, Greece. Salmonella enteritidis, Salmonella anatum and Salmonella
      bredeney were the most prevalent serovars. Isolates were examined for antibiotic
      resistance patterns and R-determinants. Resistance to at least one antibiotic was
      observed in 36 (58.1%) of them and 18 different resistant profiles were recorded.
      Nitrofurantoin-resistance was the most common (29.0%), followed by spectinomycin
      (21.0%), ampicillin (19.4%) and ticarcillin (19.4%). Fourteen (38.9%) of the
      resistant isolates possessed R-factors and resistance to ampicillin, ticarcillin,
      trimethoprim and kanamycin was easily self-transferable. However, nitrofurantoin-
      and spectinomycin-resistance although prevailing, was not found transferable even
      after mobilization. The high incidence of antibiotic resistant salmonellae among
      chicken carcasses in our hospital setting suggests the need for public health
      interventions and possible withdrawal of drug selective pressure.

PMID- 9620128
TI  - Bifidobacteria as indicators of faecal contamination in meat and meat products:
      detection, determination of origin and comparison with Escherichia coli.
AB  - Faecal contamination of meat and meat products and its origin, whether human or
      animal, was determined by using the presence of bifidobacteria as an indicator.
      Enrichment of samples in Beerens liquid selective medium was followed by
      spreading onto Columbia agar containing paromomycin. In comparison with the
      detection of Escherichia coli (E. coli) the following results were obtained from
      50 samples: E. coli. +; Bifidobacterium. +: 38; E. coli -; Bifidobacterium -: 9;
      E. coli, +; Bifidobacterium. -: 2; E. coli, -; Bifidobacterium. +: 1. From 39
      positives samples, 50 strains of bifidobacteria were isolated. Two were of human
      origin, 48 of animal origin.

PMID- 9620129
TI  - Identification, assessment and management of food-related microbiological
      hazards: historical, fundamental and psycho-social essentials.
AB  - Microbiological risk assessment aimed at devising measures of hazard management,
      should take into account all perceived hazards, including those not empirically
      identified. It should also recognise that safety cannot be "inspected into" a
      food. Rather hazard management should be the product of intervention strategies
      in accordance with the approach made mandatory in the EU Directive 93/43 and the
      USDA FSIS Pathogen Reduction HACCP system; Final Rule. It is essential too that
      the inherent variability of the biological attributes affecting food safety is
      recognised in any risk assessment. The above strategic principles may be
      conceptualised as a four-step sequence, involving (i) identification and
      quantification of hazards; (ii) design and codification of longitudinally
      integrated ("holistic") technological processes and procedures to eliminate, or
      control growth and metabolism of, pathogenic and toxinogenic organisms; (iii)
      elaboration of microbiological analytical standard operating procedures,
      permitting validation of "due diligence" or responsible care, i.e. adherence to
      adopted intervention strategies. This should be supported by empirically assessed
      reference ranges, particularly for marker organisms, while the term "zero
      tolerance" is refined throughout to tolerable safety limit; (iv) when called for,
      the need to address concerns arising from lay perceptions of risk which may lack
      scientific foundation. In relation to infectious and toxic hazards in the
      practical context the following general models for quantitative holistic risk
      assessment are presented: (i) the first order, basic lethality model; (ii) a
      second approximation taking into account the amount of food ingested in a given
      period of time; (iii) a further adjustment accounting for changes in colonization
      levels during storage and distribution of food commodities and the effects of
      these on proliferation of pathogens and toxin production by bacteria and moulds.
      Guidelines are provided to address: (i) unsubstantiated consumer concern over the
      wholesomeness of foods processed by an innovative procedure; and (ii) reluctance
      of small food businesses to adopt novel strategies in food safety. Progress here
      calls for close cooperation with behavioural scientists to ensure that investment
      in developing measures to contain risk deliver real benefit.

PMID- 9620130
TI  - Presidential address: The hour is getting late.

PMID- 9620131
TI  - Natural history of the residual infrarenal aorta after infrarenal abdominal
      aortic aneurysm repair.
AB  - PURPOSE: We determined the natural history of the residual native infrarenal
      aortic segment after conventional abdominal aortic aneurysm (AAA) repair.
      METHODS: For the retrospective arteriographic case series, 800 hundred
      translumbar aortograms (TLAs) were obtained for 272 patients, before and after
      conventional AAA repair. The main outcome measures were changes in the
      aortographic diameter and the length of the infrarenal aortic segment, corrected
      and uncorrected for magnification by normalization to the first lumbar vertebral
      body height. RESULTS: The mean follow-up time from the preoperative TLA to the
      most recent postoperative TLA was 42 months (range, 1 to 257 months). Vertebral
      body height did not change (p = 0.35). The length of the native infrarenal aorta
      cephalad to the proximal anastomosis increased a mean of 3 mm, from 23 to 26 mm
      (p = 0.001). However, in 115 patients (43%), this aortic segment elongated more
      than 5 mm, and in 63 patients (24%), it elongated more than 10 mm. The native
      residual infrarenal aorta above the proximal anastomosis dilated a mean of 1 mm,
      from 23 to 24 mm (p = 0.001), but in 21 patients (8%), it dilated more than 5 mm.
      There was a weak positive correlation between the increase in residual native
      aortic diameter and duration of follow-up. There was a negative correlation
      between this increase and the initial size. The diameters of the proximal
      anastomosis and proximal graft did not change. Marked variability in the changes
      in aortic dimensions was observed. CONCLUSIONS: A mean period of 42 months after
      conventional AAA repair, the native infrarenal aortic segment elongates and
      dilates. Although such enlargement is statistically significant, the average
      increase appears to be small. However, residual aortic cuff diameter increased
      more than 5 mm and neck length more than 10 mm in a significant number of
      patients, with potentially serious implications for endovascular treatment of
      AAA.

PMID- 9620132
TI  - Long-term survival and late complications after repair of ruptured abdominal
      aortic aneurysms.
AB  - PURPOSE: Long-term survival and late vascular complications in patients who
      survived repair of ruptured abdominal aortic aneurysms (RAAA) is not well known.
      The current study compared late outcome after repair of RAAA with those observed
      in patients who survived elective repair of abdominal aortic aneurysms (AAA).
      METHODS: The records of 116 patients, 102 men and 14 women (mean age: 72.5 (8.3
      years), who survived repair of RAAA (group I) between 1980 to 1989 were reviewed.
      Late vascular complications and survival were compared with an equal number of
      survivors of elective AAA repair matched for sex, age, surgeon, and date of
      operation (group II). Survival was also compared with the age and sex-matched
      white population of west-north central United States. RESULTS: Late vascular
      complications occurred in 17% (20/116) of patients in group I and in 8% (9/116)
      in group II. Paraanastomotic aneurysms occurred more frequently in group I than
      in group II (17 vs. 8, p = 0.004). At follow-up, 32 patients (28%) were alive in
      group I (median survival: 9.4 years) and 53 patients (46%) were alive in group II
      (median survival: 8.7 years). Cumulative survival rates after successful RAAA
      repair at 1, 5, and 10 years were 86%, 64%, and 33%, respectively. These were
      significantly lower than survival rates at the same intervals after elective
      repair (97%, 74%, and 43%, respectively, p = 0.02) or survival of the general
      population (95%, 75%, and 52%, respectively, p < 0.001). Coronary artery disease
      was the most frequent cause of late death in both groups. Vascular and graft
      related complications caused death in 3% (3/116) in group I and 1% (1/116) in
      group II. Cox proportional hazards modeling identified age (p = 0.0001),
      cerebrovascular disease (p = 0.009), and number of days on mechanical ventilation
      (p = 0.01) to be independent prognostic determinants of late survival in group I.
      CONCLUSIONS: Late vascular complications after repair of RAAA were higher and
      late survival rates lower than after elective repair. These data support elective
      repair of AAA. As two-thirds of the patients discharged after repair of RAAA are
      alive at 5 years, aggressive management of RAAA remains justified.

PMID- 9620133
TI  - Cardiac function is a risk factor for paralysis in thoracoabdominal aortic
      replacement.
AB  - PURPOSE: We studied factors that influence paralysis risk, renal function, and
      mortality in thoracoabdominal aortic replacement. METHODS: We prospectively
      collected preoperative demographic and intraoperative physiologic data and used
      univariate and multivariate analyses to correlate this data with risk factors for
      paralysis. A mathematical model of paraplegia risk was used to study the efficacy
      of paraplegia reduction strategies. We analyzed preoperative and operative
      factors for paralysis risk, renal function, and mortality for 217 consecutive
      patients surgically treated from 1984 through 1996 for 176 thoracoabdominal and
      41 thoracic aneurysms at the University of Wisconsin Hospital and Clinics. No
      patient had intercostal reimplantation or assisted circulation. One hundred fifty
      patients (group A) received cerebrospinal fluid drainage (CSFD) and low-dose
      naloxone (1 microg/kg/hour) as adjuncts to reduce the risk of paralysis. Sixty
      seven patients (group B) did not receive CSFD and naloxone. RESULTS: Seventeen
      deficits occurred in 205 surviving patients: 5 of the 147 in group A (expected
      deficits = 31) and 12 of the 58 in group B (expected deficits = 13) (p < 0.001).
      In a multivariate logistic regression model, acute presentation, Crawford type 2
      aneurysm, group B membership, and a decrease in cardiac index with aortic
      occlusion remained significant risk factors for deficit (p < 0.0001). By odds
      ratio analysis, group A patients had 1/40th the risk of paralysis of group B. The
      only significant predictor of postoperative renal function was the preoperative
      creatinine level (p < 0.0001); renal revascularization significantly improved
      renal function. The mortality rate was 1.6% (2) for patients undergoing elective
      treatment and 21% (19) for patients who had acute presentations. Acute
      presentation, age, and the preoperative creatinine level were found to be
      significant factors for operative mortality in a logistic regression model (p <
      0.001) and defined a group at high risk for death. CONCLUSIONS: CSFD and low-dose
      naloxone significantly reduce the paralysis risk associated with thoracoabdominal
      aortic replacement. A decrease in the cardiac index with aortic occlusion is a
      previously unreported variable that defines a subset of patients at higher risk
      for paralysis.

PMID- 9620134
TI  - Lower extremity arterial evaluation: are segmental arterial blood pressures
      worthwhile?
AB  - PURPOSE: Physiologic observations with blood flow waveform analysis and pressure
      measurements can document the severity of lower extremity arterial disease.
      Segmental blood pressures (SEGPs) taken at the thigh, calf, and ankle are
      commonly used, but their utility has seldom been studied. We quantified
      improvements in accuracy compared with arteriography when ankle pressures alone
      (ABI) or SEGP data were added to velocity waveforms obtained by Doppler
      ultrasound. METHODS: Continuous-wave Doppler velocity waveforms were recorded at
      common femoral (CFA), popliteal (POP), and dorsal pedal and posterior tibial
      (TIB) arterial levels. Systolic SEGP data were obtained with appropriately sized
      upper thigh, upper calf, and ankle cuffs. Waveforms, waveforms plus ABI, and
      waveforms plus SEGP data from 81 patients were randomly interpreted by 14
      technologists or physicians from four institutions blinded to clinical and
      arteriographic data. Arteriograms were assigned negative or significant, severe
      (>75% diameter stenosis) values for four segments: iliofemoral (CFA), superficial
      femoral (SFA), popliteal (POP), and infrapopliteal (TIB) arteries. A total of
      9072 segmental interpretations were analyzed. RESULTS: Compared with
      arteriography, the accuracy of waveform analysis was 83% for severe disease at
      and proximal to the CFA, 79% for SFA disease, 64% for POP disease, and 73% for
      TIB disease. Adding ABI improved the accuracy significantly (p < 0.01) to 88%
      (CFA), 86% (SFA), 70% (POP), and 85% (TIB). Accuracy was inferior when SEGP data
      replaced ABI: 86% (CFA), 85% (SFA), 70% (POP), and 80% (TIB). CONCLUSIONS: ABIs
      significantly improved Doppler waveform accuracy at all levels. Compared with
      ABI, the addition of segmental pressure to waveform data failed to improve
      accuracy. Pressure measurements above the ankle may lack cost effectiveness and
      clinical utility.

PMID- 9620135
TI  - The clinical course of asymptomatic mesenteric arterial stenosis.
AB  - PURPOSE: The incidence of subsequent symptomatic mesenteric vascular disease is
      unknown for patients who have asymptomatic mesenteric arterial stenosis. The
      purpose of this study was to determine the risk of developing acute and chronic
      mesenteric ischemia in patients identified by lateral aortography to have
      significant mesenteric artery stenosis. METHODS: From 1989 through 1995, 980
      consecutive aortograms with anteroposterior and lateral projections were reviewed
      within 1 week of arteriography to identify patients who had significant
      mesenteric stenosis but no symptoms of mesenteric ischemia. Eighty-two patients
      were found to have 50% stenosis of at least one mesenteric artery and were
      monitored by interview to determine if symptoms of acute or chronic mesenteric
      ischemia developed. RESULTS: Ten patients were lost to follow-up, and 12 patients
      were withdrawn from the study because of mild mesenteric arterial disease (1% to
      49% stenosis) in combination with more significant disease of other vessels.
      Follow-up was 1 to 6 years. The overall mortality rate was 40%, and mesenteric
      ischemia developed in four patients. Each of these four patients had significant
      (>50%) stenosis or occlusion of the celiac artery, superior mesenteric artery,
      and inferior mesenteric artery. Eighty-six percent of the 15 patients with
      significant three-vessel arterial disease had mesenteric ischemia, had other
      vague abdominal symptoms, or died. CONCLUSIONS: Patients with significant three
      vessel mesenteric arterial stenosis should be considered for prophylactic
      mesenteric arterial reconstruction. Mesenteric arterial reconstruction should be
      routine when these patients undergo aortic reconstruction for aneurysmal or
      occlusive disease.

PMID- 9620136
TI  - Comparison of North American Symptomatic Carotid Endarterectomy Trial and
      population-based outcomes for carotid endarterectomy.
AB  - PURPOSE: The North American Symptomatic Carotid Endarterectomy Trial (NASCET)
      advocated the use of carotid endarterectomy (CEA) for transient ischemic attacks
      (TIAs), nondisabling strokes, and ipsilateral high-grade stenosis in highly
      selected patients. Whether similar results are achieved when CEA is applied to an
      entire geographically defined population is unknown but important if the NASCET
      recommendations are to be applied broadly to all community patients. METHODS: To
      determine the survival rate to ipsilateral stroke after CEA for all symptomatic
      patients in a defined population, we reviewed the medical records of all patients
      residing in Olmsted County, Minn. (approximately 100,000), who underwent a CEA
      for TIA or nondisabling stroke between 1970 and 1995. Their outcomes were
      compared with the NASCET results. RESULTS: In the community of Olmsted County,
      297 patients (108 women and 189 men) underwent 322 CEAs during the study period.
      TIAs or nondisabling stroke was the indication in 254 patients (86%), whereas the
      remaining 14% had asymptomatic stenosis. After CEA for symptomatic lesions,
      survival rate free of ipsilateral stroke was 97% at 2 years, 93% at 5 years, and
      92% at 10 years. These results are similar to the NASCET survival rates free of
      ipsilateral stroke at 2 years (91%). However, the 30-day postoperative stroke
      rate for patients older than 80 years was significantly higher than that for
      patients younger than 80 years. CONCLUSIONS: When the NASCET results are compared
      with a population-based experience in which all symptomatic patients undergoing
      CEA were analyzed, the early outcomes were similar. Our population-based data
      also document the remarkably durable long-term results of CEA in preventing
      stroke and present another benchmark for carotid stent angioplasty.

PMID- 9620137
TI  - A review of 100 consecutive reconstructions of the distal vertebral artery for
      embolic and hemodynamic disease.
AB  - PURPOSE: The aim of our study was to assess the outcome of distal vertebral
      artery (VA) reconstructions through a retrospective review conducted at a
      university-affiliated referral center. METHODS: One hundred consecutive distal VA
      reconstructions had been performed during a period of 14 years (98 patients) and
      included reversed saphenous vein bypass from the ipsilateral common, internal, or
      external carotid to the third portion of the VA at the C1-2 level (68
      reconstructions) or the C0-1 level (4); transposition of the external carotid or
      its occipital branch to the VA (23); and transposition of the third portion of
      the VA onto the internal carotid artery (2). Other methods were used in 3
      additional patients. Eighteen patients underwent concomitant carotid operations,
      and 1 patient underwent a concomitant subclavian transposition. Symptoms were
      present in 98% of patients and included vertebrobasilar ischemia (89%),
      vertebrobasilar plus hemispheric ischemia (7%), and hemispheric ischemia (2%).
      Two asymptomatic patients with bilateral carotid occlusions underwent operations
      to provide a single artery for cerebral perfusion (2%). Sixty-three lesions were
      atherosclerotic, 18 were dynamic bony compressions, and 14 were dissection,
      fibromuscular dysplasia, arteritis, or aneurysm. Five had miscellaneous anatomic
      indications. RESULTS: Stroke caused the four perioperative deaths that occurred.
      There was one occurrence of nonfatal hemispheric stroke. Routine postoperative
      arteriography identified 16 graft abnormalities; 11 patients underwent attempted
      revision. The introduction of the use of intraoperative angiography in 1990,
      halfway through the series, lowered the incidence of graft abnormalities from 28%
      to 4% and the incidence of perioperative death from 6% to 2%. Eighty-seven
      percent of patients had complete or significant resolution of symptoms. Follow-up
      ranged from 1 to 168 months (mean, 79 months). Ten patients were lost to follow
      up. Twenty late deaths occurred; none were stroke related. Five reconstructions
      required late revision. The cumulative primary patency at 5 and 10 years was 75%
      +/- 6 and 70% +/- 7 (mean +/- SE), respectively; cumulative secondary patency was
      84% +/- 5 and 80% +/- 6 at 5 and 10 years, respectively. Median survival was 107
      months. CONCLUSIONS: Distal VA reconstruction provides excellent long-term
      patency and stroke protection. Intraoperative angiography is mandatory.

PMID- 9620138
TI  - Carotid endarterectomy in octogenarians: early results and late outcome.
AB  - PURPOSE: This study was undertaken to determine the safety and efficacy of
      carotid endarterectomy (CEA) in the octogenarian population at the Cleveland
      Clinic. METHODS: From 1989 to 1995, 182 CEAs were performed among 167
      octogenarians (98 men, 69 women) with a mean age of 83 years (median, 83 years;
      range, 80 to 93 years). One hundred procedures (55%) were performed for severe
      asymptomatic stenosis, whereas 48 (26%) were performed for hemispheric transient
      ischemic attacks (TIAs) or amaurosis fugax, 24 (13%) for prior stroke, and 10
      (5%) for vertebrobasilar symptoms. Thirteen CEAs (7%) were combined with
      myocardial revascularization, and another five (3%) represented carotid
      reoperations. Nine arteriotomies (5%) were closed primarily, whereas the
      remaining 173 (95%) were repaired using either vein patch angioplasty (141, 77%)
      or synthetic patches (32, 18%). Two patients were lost to follow-up, but late
      information was available for 165 patients (180 operations) at a mean interval of
      2.7 years (median, 2.4 years; maximum, 7.4 years). RESULTS: Considering all 182
      procedures, there were five early (<30 days) postoperative neurologic events
      (2.7%), including three strokes (1.6%) and two TIAs (1.1%). An additional 15
      neurologic events occurred during the late follow-up period, consisting of 11
      strokes (6.1%) and four TIAs (2.2%). The Kaplan-Meier estimated 5-year rate of
      freedom from stroke was 85% (95% confidence interval [CI], 77% to 93%). There was
      one early postoperative death (0.6%) of cardiac complications 9 days after CEA.
      The estimated 5-year survival rate was 45% (95% CI, 33% to 57%), and the 5-year
      stroke-free survival rate was 42% (95% CI, 30% to 53%). Multivariable analysis
      yielded age at operation (p = 0.001), abnormal creatinine level (p = 0.025), and
      chronic obstructive pulmonary disease (p = 0.019) as variables that significantly
      influenced the survival rate. The presence of chronic obstructive pulmonary
      disease (p = 0.009) and, surprisingly, a lesser degree of contralateral internal
      carotid stenosis (p = 0.003) were found to be significantly associated with
      stroke after CEA. Causes of late death were cardiovascular in 16 patients (30%),
      unknown in 13 (24%), carcinoma in six (11%), stroke in six (11%), and
      miscellaneous in 13 (24%). CONCLUSIONS: We conclude that CEA may be safely
      performed in selected octogenarians with carotid stenosis, and that the majority
      of these patients live the rest of their lives free from stroke. Therefore, age
      alone should not exclude otherwise-qualified candidates from consideration for
      CEA.

PMID- 9620139
TI  - Carotid plaque morphology correlates with presenting symptomatology.
AB  - PURPOSE: In carotid artery disease, correlation of carotid plaque morphology with
      the patient's presenting symptoms has drawn conflicting conclusions. The purpose
      of this series was to correlate carotid plaque characteristics with the
      presenting symptoms from a large cohort of patients who underwent operation for
      carotid artery disease. METHODS: From a series of 1252 consecutive patients who
      underwent carotid endarterectomy, presenting symptoms were divided into three
      groups: transiently symptomatic (transient ischemic attack [TIA] or amaurosis
      fugax), prior stroke, and asymptomatic. Plaque characteristics, including
      ulceration, intraplaque hemorrhage, and degree of stenosis, were recorded
      prospectively for 1008 procedures. All endarterectomy specimens were inspected
      during the procedure, and plaque characteristics were recorded immediately after
      operation. RESULTS: There was a higher incidence of plaque ulceration in the
      transiently symptomatic and prior stroke groups (391 of 508 [77%] and 91 of 115
      [79%]) than in the asymptomatic cohort (231 of 385 [60%]; p < 0.0001, chi2 test).
      There was no significant difference in the incidence of plaque hemorrhage between
      the transiently symptomatic and prior stroke patients compared with the
      asymptomatic patients. There was no statistical difference for ulcerated plaque
      or plaque hemorrhage between the transiently symptomatic and prior stroke group.
      Intraplaque hemorrhage occurred more frequently in patients with high-grade
      stenosis (90% to 99%) than in those with less than 90% stenosis (202 of 299 [68%]
      versus 97 of 299 [32%]; p = 0.01, chi2 test). CONCLUSIONS: On gross examination
      of the carotid specimen in the operating room, plaque ulceration correlates with
      an initial presentation of amaurosis fugax, TIA, or prior stroke compared with
      patients operated on for asymptomatic disease. The presence of intraplaque
      hemorrhage is associated with more advanced stenosis of the internal carotid
      artery. These findings suggest that plaque morphology does play an important role
      in the presentation of carotid artery disease.

PMID- 9620140
TI  - Aggressive management of vascular injuries of the thoracic outlet.
AB  - PURPOSE: We present a review of 35 patients who underwent an operation for
      subclavian (n = 18) or axillary (n = 17) vessel injury. In some patients, both an
      artery and a vein were damaged, resulting in a total of 30 arterial and 16 venous
      injuries. METHODS: The wounding source included a gunshot (n = 19), a stab wound
      (n = 9,) and blunt trauma (n = 7). Seven patients had hypotension and were taken
      immediately to the operating room. Seventeen patients had diminished or absent
      pulses, whereas 13 patients had normal pulses despite an arterial injury.
      Associated injuries included nerve injury (n = 15), pneumohemothorax (n = 5), and
      fractures (n = 7). Angiography in 21 patients demonstrated an intimal flap (n =
      8), extravasation (n = 5), a pseudoaneurysm (n = 3), an arteriovenous fistula (n
      = 2), and occlusion (n = 1). Two angiograms were normal. Arterial repair was
      accomplished by interposition graft (n = 17), primary repair (n = 9), patch
      angioplasty (n = 3,) and ligation (n = 1). RESULTS: No functional deficits
      occurred in patients with an isolated vascular injury. Seven patients with
      associated brachial plexus injuries experienced severe disability. One arm of a
      patient was amputated. Two patients died. CONCLUSIONS: The use of angiography
      helps to confirm and localize injuries. Prompt correction of the vascular injury
      avoids disability resulting from ischemia. Although the amputation rate is low
      with vascular repair, the functional disability resulting from associated nerve
      injuries can be devastating.

PMID- 9620141
TI  - Controlled delivery of vascular endothelial growth factor promotes
      neovascularization and maintains limb function in a rabbit model of ischemia.
AB  - PURPOSE: Vascular endothelial growth factor (VEGF) modulates new blood vessel
      development and growth and has been suggested as a potential therapeutic agent
      that could alleviate debilitating claudication in patients. The objective of this
      study was to determine whether controlled, local delivery of a low dose of VEGF
      from an osmotic pump could promote neovascularization, limb perfusion, and
      functional improvements in the hind limbs of rabbits rendered partially ischemic
      by surgery. The effects of VEGF were compared with those of the vasodilator
      nitroglycerin (NTG) and to saline administered similarly. METHODS: Thirty rabbits
      were randomly assigned to either VEGF (n = 10), NTG (n = 10), or saline (n = 10)
      treatment groups. Partial ischemia was induced in each left hind limb by surgical
      ligation of the common and superficial femoral arteries, leaving the internal
      iliac artery intact. The right limb of each animal served as a nonischemic
      control. Immediately after vessel ligations, a 28-day osmotic pump was implanted
      to deliver VEGF (0.22 microg/kg/day), NTG (17.8 microg/kg/day), or saline
      solution into the common iliac artery just proximal to the ligation site.
      Comparative vascularity between ischemic and nonischemic limbs within treatment
      groups and between groups was evaluated by (1) capillary counts from
      representative fields of hematoxylin and eosin stained muscle tissue taken from
      hind limbs at day 40; (2) digitized arteriograms of ischemic legs at day 40,
      which were used to quantify the complexity of vascular branching (fractal
      dimension index) and the total extent of vascularization (vascular density
      index); (3) measuring capillary refill times in ischemic limbs; and (4)
      observations of functional and trophic changes in ischemic limbs. Statistical
      differences between treatment groups were evaluated by one-way ANOVA. RESULTS:
      Complexity of vascular branching and vascular density were significantly greater
      (p < 0.001) in VEGF-treated ischemic limbs compared with NTG- and saline-treated
      ischemic limbs. By postoperation day 14, all VEGF-treated ischemic limbs had
      restored capillary refill (p < 0.001), new hair growth, and greatly improved limb
      function and appearance. Saline-treated limbs exhibited ischemic changes, with
      poor capillary refill and negligible limb function. Capillary refill in NTG
      treated ischemic limbs did not differ significantly from saline-treated limbs.
      Ischemic VEGF-treated limbs had significantly more capillaries compared with both
      ischemic and nonischemic limbs in saline-treated animals (p < 0.05). Ischemic NTG
      treated limbs also had significantly more capillaries compared with ischemic
      limbs in saline-treated animals (p < 0.05). Because of high variability, however,
      capillary counts in VEGF-treated ischemic limbs did not differ significantly from
      those of contralateral nonischemic limbs, or from capillary counts in either
      ischemic or nonischemic limbs of NTG-treated rabbits. CONCLUSIONS: Controlled
      release of microgram quantities of VEGF significantly enhanced neovascularization
      and vascular perfusion in ischemic limbs compared with controls in this rabbit
      model of partial ischemia. In addition, VEGF-treated ischemic limbs demonstrated
      near-normal function and appearance, whereas NTG- and saline-treated ischemic
      controls remained noticeably impaired. This novel approach of VEGF delivery may
      prove clinically useful either alone or combined with revascularization
      procedures.

PMID- 9620142
TI  - Heparin-bonded grafts induce platelet aggregation in the presence of heparin
      associated antiplatelet antibodies.
AB  - PURPOSE: Thromboresistant synthetic grafts should decrease the frequency of graft
      thromboses and could be useful in bypasses to small arteries and to arteries with
      compromised flow. Heparin-bonded grafts (HBG) have been developed. Studies were
      done to determine whether the heparin bond is permanent and whether the HBG would
      aggregate platelets in the presence of heparin-associated antiplatelet antibodies
      (HAAbs). METHODS: We studied an 8 mm HBG from company A (HBGA) and 8 mm and 6 mm
      HBGs from company B (HBGB-8 and HBGB-6), none of which is available for clinical
      use in the United States. Five 1 cm long segments of HBGA, HBGB-8, and HBGB-6
      were incubated for 24 hours in 5 ml of plasma, 10 ml of saline, or 10 ml of
      Ringer's lactate. After incubation, 1 ml was obtained from each solution and
      assayed for heparin. Segments of each graft that leached off an equivalent of 1 U
      of heparin/ml (i.e., 1 mm2 of HBGA, 5 mm2 of HBGB-8, and 20 mm2 of HBGB-6) were
      incubated with 0.15 ml of plasma with HAAbs (six samples per graft) for 30
      minutes at 25 degrees C. The grafts were removed, and 0.1 ml of normal-donor,
      platelet-rich plasma was added. The samples were placed in an aggregometer and
      allowed to react until positive aggregation occurred or 27 minutes had elapsed.
      Segments of non-heparin-bonded polyester grafts served as controls. RESULTS:
      Heparin leached off all grafts in plasma (mean values: HBGA, 83.4 U of
      heparin/ml; HBGB-8, 4 U of heparin/ml; HBGB-6, 6.2 U of heparin/ml). In normal
      saline, the mean heparin concentrations were lower (HBGA, 10.8 U of heparin/ml;
      HBGB-8, 0 U of heparin/ml; HBGB-6, 0.01 U of heparin/ml. The mean heparin
      concentration after incubation in Ringer's lactate were 10 U of heparin/ml for
      HBGA, 0 U of heparin/ml HBGB-8, and 0.22 U of heparin/ml HBGB-6. All of the HBGs
      induced platelet aggregation inHAAb-positive plasma. None of the control grafts
      induced platelet aggregation in HAAb-positive plasma. CONCLUSIONS: All HBGs
      leached heparin into plasma, and all induced platelet aggregation in the presence
      of HAAbs. The possibility of sensitizing patients to heparin leeching from a HBG
      with the activation of platelets and secondary thrombosis strongly suggests that
      HBG be used with great caution. Other methods for inducing graft
      thromboresistance should be developed.

PMID- 9620143
TI  - Improved adherence of genetically modified endothelial cells to small-diameter
      expanded polytetrafluoroethylene grafts in a canine model.
AB  - PURPOSE: A significant limitation to using genetically modified endothelial cells
      (ECs) to seed prosthetic grafts before implantation has been poor cell adherence
      to the graft lumen. Methodologic changes to improve cell adherence were evaluated
      in a canine carotid interposition graft model using 4 mm interior diameter
      expanded polytetrafluoroethylene. METHODS: ECs harvested from external jugular
      veins were grown in culture, with 80% of the cells from each culture transduced
      by incubation with an LXSN-type retroviral vector carrying a gene for human
      prourokinase and a neomycin resistance gene for selection in antibiotic G418.
      Control grafts had passive luminal coating with fibronectin and were seeded with
      transduced ECs immediately after G418 selection; these grafts were incubated for
      2 days before implantation. Experimental grafts had fibronectin forcefully
      squeezed through the interstices and were seeded with ECs that had recovered in
      culture for 5 days after G418 selection; these grafts were incubated for 4 days
      before implantation. For each control (n = 9) and experimental (n = 12) graft, a
      graft prepared in the same fashion but seeded with the remaining autologous
      nontransduced cells was placed in the contralateral carotid artery. Grafts were
      explanted after 30 days and were evaluated for patency, thrombus-free surface
      area, and cell-free surface area. RESULTS: No significant differences in patency
      rates were seen between any groups. The thrombus-free surface area was improved
      for experimental grafts (90%) compared with control grafts (76%), but this
      improvement did not achieve statistical significance. The cell-free surface area
      for transduced cells on experimental grafts was 65% compared with 96% for control
      grafts (p = 0.021) and was comparable with that for nontransduced cells on both
      control grafts (62%) and experimental grafts (51%; p = 0.201). CONCLUSIONS:
      Adherence of genetically modified endothelial cells to small-diameter expanded
      polytetrafluoroethylene grafts in an in vivo physiologic flow model is
      significantly improved when cells have a more prolonged recovery from G418
      selection, when the graft lumen is more uniformly coated with fibronectin before
      EC seeding, and when seeded grafts are left longer in culture before implantation
      to develop cell lining stability. The short-term patency rate of these seeded
      grafts is not affected by increased cell retention; long-term graft patency data
      and luminal healing require further evaluation.

PMID- 9620144
TI  - Low flow enhances platelet activation after acute experimental arterial injury.
AB  - PURPOSE: Vascular smooth muscle cell (VSMC) proliferation and migration to the
      subintima or intimal hyperplasia (IH) occur after arterial injury and are thought
      to be induced by mitogenic factors released from activated platelets. Because low
      flow (LF) and shear have been attributed to the localization and progression of
      IH, we postulated that hemodynamic factors may regulate the degree of platelet
      activation, as measured by plasma thromboxane B2 (TXB2) and platelet-derived
      growth factor-AB (PDGF-AB) release at regions of experimental arterial injury.
      METHODS: The right common carotid artery (CCA) was subjected to balloon injury in
      18 New Zealand White male rabbits. Flow in the injured CCA was reduced by out
      flow ligation (LF group, n = 6) or increased by ligation of the left CCA (high
      flow [HF] group, n = 6). In six other animals, flow was preserved (normal flow
      [NF] group). Mean blood flow and pressure in the right CCA were measured
      thereafter at 10 and 30 minutes. Plasma TXB2 and PDGF-AB levels were determined
      with the enzyme-linked immunosorbent assay method in each animal with blood
      samples taken systematically before injury (baseline) and in the distal CCA at
      similar time points. RESULTS: At 10 minutes, mean blood flow was reduced from 20
      +/- 2 ml/min in the NF group to 7 +/- 1 ml/min in the LF group animals (p < 0.01)
      and increased to 32 +/- 2 ml/min in the HF group animals (p < 0.05). Mean
      arterial blood pressure did not differ among the groups. Hemodynamic parameters
      were similar at 10 and 30 minutes. TXB2 levels were more than fourfold greater in
      the LF group than in the HF and NF groups at both time points (p < 0.05). In
      addition, there was a twofold increase in plasma PDGF-AB level at 10 minutes in
      the LF group compared with baseline levels (p < 0.05). CONCLUSION: Platelet
      activation at regions of acute vascular injury was determined to be flow
      dependent. Upregulated platelet activity in low flow conditions may be due to
      increased platelet exposure time to subendothelial collagen and is greatly
      attenuated if normal or increased flow is present.

PMID- 9620145
TI  - Protein kinase C isoforms in human aortic smooth muscle cells.
AB  - PURPOSE: To identify the protein kinase C (PKC) isoforms in human arterial smooth
      muscle cells (SMC) and define their subcellular location in the resting state and
      in response to the PKC activator, 12-O-tetradecanoylphorbol 13-acetate (TPA).
      METHODS: Arterial SMC cultures established from transplant donor aorta were
      treated with 100 nM TPA or control media, then mechanically lysed. PKC from the
      soluble and particulate fraction were separated by centrifugation, and protein
      normalized immunoblots were performed with antibodies to the PKC isoforms alpha,
      betaI, betaII, delta, epsilon, gamma and zeta. Bands were detected by enhanced
      chemiluminescence and analyzed densitometrically, with results expressed as the
      mean percentage of each fraction +/- SEM. Translocation was defined as a
      significant (p < 0.05) change in the particulate fraction for each isoform.
      Immunofluorescent staining of cultured SMC visualized the resting location and
      stimulated translocation of each isoform. RESULTS: Isoforms alpha and betaI were
      detected primarily in the soluble fraction, translocating to the particulate
      fraction with TPA stimulation (p < 0.0001). The isoforms betaII, delta, and
      epsilon were found primarily in the particulate fraction and did not translocate.
      Immunofluorescent staining confirmed these locations. Neither gamma or zeta were
      detected in these SMC. CONCLUSIONS: The PKC isoforms expressed in human arterial
      SMC differ from those reported in animal models. Their specific locations and
      response to stimulation suggest unique functions in cellular regulation and
      provide the groundwork for further investigation into their role in the
      development of vascular disease and regulation of matrix metabolism.

PMID- 9620146
TI  - Bypass to the perigeniculate collateral vessels. A useful technique for limb
      salvage: preliminary report on 22 patients.
AB  - PURPOSE: We describe our initial experience with the use of perigeniculate
      vessels as outflow tracts in infrainguinal revascularizations for critical limb
      ischemia. METHODS: Twenty-two such reconstructions were carried out in 20
      patients over a 2-year period. Indications for surgery consisted of tissue loss
      in 9 patients and rest pain in the other 13 patients. Inflow was obtained from
      the femoral vessels. A variety of graft materials were used, including saphenous
      vein (16 patients), polytetrafluoroethylene (2 patients), composite (1 patient),
      and arterial homografts (3 patients). The perigeniculate vessels used were the
      medial sural artery to the gastrocnemius (arteria suralis) in 16 patients and the
      highest genicular artery (arteria genu suprema) in the other 6 patients. These
      vessels were approached via a medial above-the-knee popliteal-type exposure.
      RESULTS: There were three postoperative deaths. Mean follow-up for the other 17
      patients averaged 12 months (range, 3 to 37 months). Three grafts failed
      (thrombosis) during follow-up, leading to two above-the-knee amputations. One
      graft stenosis was treated with percutaneous angioplasty. The average
      postoperative increase in the ankle-brachial index was 0.20. CONCLUSION: These
      early results appear promising with a 1-year primary patency rate of 77%,
      assisted primary patency rate of 85%, and a limb-salvage rate of 90% according to
      the Kaplan-Meier life-table method. This technique is particularly useful when
      adequate length saphenous vein is not available, no other outflow vessels are
      available, or other outflow vessels are very calcified and not safely clamped.
      The continued study of the long-term effectiveness is warranted.

PMID- 9620147
TI  - Shortening and reimplantation for tortuous internal carotid arteries.
AB  - PURPOSE: The purpose of this study was to assess the outcome after the shortening
      and reimplantation of tortuous internal carotid arteries to prevent kinking after
      endarterectomy. METHODS: Through a review of prospective records, we studied
      patients who underwent carotid endarterectomy (CEA) (n = 233) between 1993 and
      1996 who had symptomatic stenosis of the internal carotid artery (ICA) of more
      than 70%. An elongated proximal ICA was excised, and the ICA was reimplanted into
      the bifurcation in 30 (13%) patients, with additional patch angioplasty in 5
      patients. Of the remaining 203 patients, 50 (21%) had Dacron patch angioplasty,
      and the rest had conventional CEA with simple closure. RESULTS: In the
      reimplanted group, one patient had a minor stroke with complete recovery on
      discharge. Three patients (10%) had neck hematomas requiring reexploration, but
      in none of these was the bleeding from the artery. At mean follow-up of 15
      months, 93% of the arteries were widely patent. Significant stenosis secondary to
      neointimal hyperplasia was detected in only two patients, for a restenosis rate
      of 6.7%, which is in line with other published reports. In the control group, 8
      (3.9%) patients had perioperative transient ischemic attacks, 5 (2.5%) had
      strokes, and 13 (6.4%) had hematomas requiring evacuation. At follow-up, 14
      (6.9%) of the arteries had restenosed. CONCLUSION: In carotid surgery,
      reconstructive techniques must be tailored to operative findings. Excision of a
      tortuous elongated proximal ICA with reimplantation is not associated with
      additional mortality or morbidity rates over those of conventional CEA alone and
      has the advantage of removing disease at the bifurcation. This procedure was
      carried out in 13% of our patients and should be a procedure with which the
      vascular surgeon is familiar.

PMID- 9620148
TI  - Factors affecting the results of surgery for chronic critical leg ischemia--a
      nationwide survey. Finnvasc Study Group.
AB  - PURPOSE: To assess the factors affecting immediate outcome of surgery for chronic
      critical leg ischemia, especially the influence of surgeon's caseload and
      hospital volume. METHODS: The data of Finnvasc registry were retrospectively
      analyzed. A total of 11,747 surgical vascular reconstructions included 1,761
      operations for chronic critical leg ischemia during 1991 to 1994. RESULTS: The 30
      day postoperative leg amputation rate was 7.5% and the mortality rate 4.7%.
      Diabetes, previous vascular surgery or amputation, preoperative ulcer or
      gangrene, a surgeon's annual caseload fewer than 10 operations, and hospital
      volume fewer than 20 operations for chronic critical leg ischemia adversely
      affected amputation rates. The presence of coronary artery disease and renal
      dysfunction increased postoperative mortality rates. Both amputation rates and
      postoperative mortality rates were affected by the type of procedure.
      CONCLUSIONS: A surgeon's caseload and hospital volume affect amputation rate, but
      not mortality rate, in patients operated for chronic critical leg ischemia.

PMID- 9620149
TI  - Videoendoscopic thoracic aorta-to-femoral artery bypass. A feasibility study in a
      canine model.
AB  - PURPOSE: This study was undertaken to determine whether videoendoscopic thoracic
      aorta-to-femoral artery bypass is a technically feasible operation. METHODS: An
      acute canine study involving five mongrel dogs was carried out. After the dogs
      had been given a general anesthetic, the femoral arteries were exposed in the
      traditional fashion. On the left side, a retroperitoneal, retrorenal tunnel was
      extended from the common femoral artery to the diaphragm. Under videoendoscopic
      control, the tunnel was opened through the posterior thoracic attachments of the
      diaphragm into the thoracic cavity. A Dacron graft was tunneled from the thoracic
      cavity on the left to the left groin. The thoracic aorta was controlled with a
      side-biting clamp, and an endoscopically performed end graft-to-side thoracic
      aortic anastomosis was created. After completion of the thoracic anastomosis, the
      left femoral anastomosis was created in a traditional manner. A left-to-right
      femoral bypass completed the lower extremity vascular procedure. An open
      thoracotomy was avoided. RESULTS: Videoendoscopic thoracic aorta-to-femoral
      artery bypass was successfully performed in all five animals. All components of
      the thoracic procedure, including exposure, dissection, vessel control, cross
      clamping, and anastomosis, were performed through the thoracic ports with
      conventional laparoscopic instruments. Blood loss was minimal. All animals
      survived the procedure before being killed. CONCLUSION: Videoendoscopic thoracic
      aorta-to-femoral artery bypass is a technically feasible operation in a canine
      model. Advantages of this unique approach over the experimental laparoscopic and
      the traditional transperitoneal open aortofemoral bypass include ease of aortic
      exposure, ability to control a segment of disease-free aorta, and anastomosis in
      a disease-free segment of aorta. Potential advantages include decreased
      perioperative morbidity rates with the videoendoscopic approach. Before there is
      clinical consideration of this surgical approach, long-term experiments are
      required to demonstrate the safety of the procedure.

PMID- 9620150
TI  - Somatostatin gene transfer and expression in endothelial cells.
AB  - PURPOSE: The antiproliferative and antisecretory effects of somatostatin have
      many potential uses in the clinical setting. Retroviral gene transfer of
      somatostatin to endothelium is a potential means of local delivery of this
      peptide to specific vascular beds. This investigation was designed to determine
      whether transduced endothelial cells (ECs) could produce and post-translationally
      process somatostatin. METHODS: Cultured canine venous, rat aortic, and rat
      microvascular ECs were transfected with retroviruses containing a human
      somatostatin cDNA or a control beta-galactosidase gene. Total and isoform
      somatostatin production and uniformity of beta-galactosidase expression were
      analyzed, as were the effects of somatostatin production on EC proliferation.
      RESULTS: Somatostatin-transduced canine venous ECs, but not rat ECs, produced
      approximately 10 times as much total somatostatin as did control-transfected ECs
      (450 +/- 32 vs 49 +/- 10 pmol/L, p < 0.05). The predominant isoform of
      somatostatin produced was somatostatin-14. Production of somatostatin was stable
      with passage and did not impair the growth of canine ECs. The failure of rat ECs
      to produce somatostatin correlated with nonuniform expression of beta
      galactosidase, suggesting that promoter silencing was responsible for failure of
      transgene expression. CONCLUSION: Retroviral gene transfer of somatostatin to
      canine ECs results in the production of physiologically relevant concentrations
      of biologically active somatostatin. Significant species differences exist in EC
      production of somatostatin, with promoter silencing being a potential mechanism
      of failure of gene expression. Gene therapy strategies using retroviral transfer
      of somatostatin to ECs may allow somatostatin delivery to focal areas of the
      vasculature.

PMID- 9620152
TI  - Angiosarcoma presenting as an occluded popliteal artery pseudoaneurysm.

PMID- 9620151
TI  - Thrombin activates MAPKAP2 kinase in vascular smooth muscle.
AB  - PURPOSE: Thrombin mediates hemostasis by promoting thrombus development and
      vasospasm, which reduces the size of the arterial injury. Thrombin stimulation of
      vascular smooth muscle is associated with activation of mitogen-associated
      protein kinase. The purpose of this investigation was to determine the subsequent
      cellular signaling events in thrombin-stimulated vascular smooth muscle
      contraction. METHODS: Contractile responses of bovine carotid artery smooth
      muscle were determined in a muscle bath and compared with phosphorylation events
      with two-dimensional gel electrophoresis. The activity of a novel kinase, mitogen
      activated protein kinase-activated protein-2 kinase (MAPKAP2 kinase), was
      determined by immunoprecipitation and a phosphotransferase assay. A small heat
      shock protein, HSP27, was identified with immunoblotting. RESULTS: Thrombin
      induces contraction of vascular smooth muscle and is associated with increased
      activity of MAPKAP2 kinase and increased phosphorylation of HSP27. Multiple
      isoforms of HSP27 are the predominant phosphoproteins in vascular smooth muscle,
      and peptide mapping suggests that the isoforms of HSP27 are structurally related
      and phosphorylated within similar peptide sequences. CONCLUSIONS: Activation of
      the MAPKAP2 kinase pathway and phosphorylation of HSP27 are associated with
      thrombin-induced contraction of vascular smooth muscle.

PMID- 9620153
TI  - Endovascular treatment of abdominal aneurysmal aortitis in Behcet's disease.
AB  - Arterial complications of Behcet's disease are rare and affect mainly the aorta
      and iliac arteries. Perforation of the arterial wall is the most common lesion,
      predisposing to false aneurysm or rupture. Open surgical repair is difficult, and
      anastomotic false aneurysms often occur because of aortic wall fragility. We
      report here the case of using a bifurcated stent to treat aortoiliac false
      aneurysms in a 37-year-old patient. Endovascular repair could be an alternative
      treatment of aneurysmal manifestations in Behcet's disease.

PMID- 9620154
TI  - In situ autogenous reconstruction of the thoracoabdominal aorta and branches for
      treatment of an infected thoracoabdominal aortobifemoral bypass graft.
AB  - Graft infection is an uncommon but potentially lethal complication of prosthetic
      aortic repair. We describe a novel technique for upper abdominal aortic and
      visceral revascularization after percutaneous drainage and antibiotics failed to
      cure a thoracofemoral prosthetic graft infection. One week after axillofemoral
      and femorofemoral bypass grafting, the infected thoracoabdominal graft was
      removed and a bifurcated iliac artery autograft was used to replace the upper
      abdominal aorta and revascularize the abdominal viscera. The infected graft was
      removed from the thorax and retroperitoneum, the infection resolved, and the
      patient remained well until his death of lung cancer 9 years later.

PMID- 9620155
TI  - Regarding "Reduction in aortic aneurysm size: early results after endovascular
      graft replacement".

PMID- 9620156
TI  - Justice for all?

PMID- 9620157
TI  - The question of welfare reform and refugee Fo's answer.

PMID- 9620158
TI  - Administrative update: utilization of services. I. Comparing use of public and
      private mental health services: the enduring barriers of race and age.
AB  - Data from the NIMH-Epidemiologic Catchment Area Project were used to predict
      differential use of private versus public outpatient mental health services, a
      salient concern in integrating public and private services in market-based health
      care reform efforts. Having a recent psychiatric disorder, being age 25-44,
      female, white, of higher educational level, and unmarried increase the odds of
      any mental health service use. However, odds of treatment in the public sector
      are increased for males, African Americans, those with low educational and income
      levels, and odds are markedly decreased for the elderly, suggesting significant
      barriers to care for these mentally ill subpopulations.

PMID- 9620159
TI  - Administrative update: utilization of services. II. Utilization of mental health
      services in a tri-ethnic sample of adolescents.
AB  - In our study of a tri-ethnic sample of 2528 junior and high school students, we
      examined utilization of outpatient mental health services in relation to a number
      of variables cited in the literature as leading to potential biases and barriers
      to care. These include: age, gender, ethnicity, socioeconomic status, family size
      and composition, and linguistic fluency in Hispanic youth. The impact of service
      availability was examined through differences between the two regions studied: a
      well-served region of coastal southeast Texas and the markedly under served lower
      Rio Grande Valley. The impact of symptomatology was evaluated using the total
      problem score on the Youth Self Report by Achenbach. Hispanic youth had
      significantly lower mean service utilization than non-Hispanic whites. Multiple
      regression analyses demonstrated that socioeconomic status and family composition
      had a greater relative impact on utilization than all other non-clinical factors,
      both for the total sample as well as for the Hispanic sample. Ethnicity may play
      a significant role in child mental health services utilization through its close
      association to socioeconomic status.

PMID- 9620160
TI  - Administrative update: utilization of services. III. Factors affecting emergency
      service utilization at a rural community mental health center.
AB  - Various factors may contribute to cyclical fluctuations in mental health
      emergency service utilization. Information regarding service utilization patterns
      would assist the planning and administration of such programs. Five years of data
      on emergency service contacts at a rural community mental health center were
      analyzed retrospectively in order to clarify which of an array of potential
      factors actually affect the utilization of emergency services. One way analyses
      of variance (ANOVA) or analogous nonparametric tests were performed. Furthermore
      analyses of significant group differences were performed by means of multiple
      comparison tests and confidence intervals. Significant associations with number
      of emergency contacts were found for season, day of week, holidays, school
      vacations and weather conditions. This study helps to elucidate those factors
      affecting psychiatric emergency service utilization at a rural community mental
      health center. Such factors may differ from those affecting other indicators of
      psychopathology.

PMID- 9620161
TI  - Detecting alcohol use disorders in the severely mentally ill.
AB  - The frequent co-occurrence of alcoholism with serious mental illnesses ("dual
      diagnosis") necessitates that clinicians are able to recognize its presence in
      people with disabling mental illnesses. This study demonstrates that
      professionals often miss the diagnosis, but that their ability to detect
      alcoholism can be greatly enhanced by the use of a simple screening tool. Members
      of an urban psychosocial rehabilitation program who received psychiatric
      treatment in an affiliated outpatient clinic were interviewed after their clinic
      therapists and rehabilitation counselors had been asked questions pertaining to
      their general health and substance use. The members were interviewed with two
      screening tests, the CAGE and the SMAST, and a clinical DSM-III-R diagnosis of
      alcohol use disorder was established. Both the SMAST and CAGE had good
      sensitivity and the addition of a screener enhanced the clinicians' ability to
      detect alcohol use disorders.

PMID- 9620162
TI  - Patterns, predictors and gender differences in HIV risk among severely mentally
      ill men and women.
AB  - A number of studies have established high human immunodeficiency virus (HIV)
      seroprevalence among severely mentally ill men and women living in large urban
      areas. Much less research has characterized the patterns of risk behavior that
      contribute to elevated vulnerability to HIV/AIDS among the mentally ill, as well
      as psychological, situational, and gender-related influences on risk in this
      population. One-hundred thirty-four severely mentally ill men and women who
      reported sexual activity outside of an exclusive relationship or with high-risk
      partners completed an extensive measure battery concerning HIV risk. Knowledge
      about HIV was low and sexual risk behavior levels were high in the sample. On
      average, condoms were used in only 32% of intercourse occasions in the past three
      months, and nearly one-half of participants reported multiple sexual partners in
      the same period. Patterns common in the sample were sex associated with substance
      use; coerced sex, bartering sex for money, food, clothes, or a place to stay; and
      sex with injection drug user partners. Factors predictive of greater risk were
      being female, presently being in a relationship, perceiving oneself to be at
      risk, high levels of alcohol use, and weak risk reduction behavioral intentions.
      Mental health programs serving severely mentally ill men and women are reaching a
      population at elevated risk for contracting HIV infection, and can serve as a
      venue for targeted HIV prevention interventions.

PMID- 9620163
TI  - Psychosocial adjustment in middle eastern adolescents: the relative impact of
      violent vs. non-violent social disorganization.
AB  - The relationship between extreme social change and the psychological adjustment
      of adolescents undergoing such change was examined. The impact of extreme social
      change relative to other conditions of catastrophic social disorganization such
      as chronic social conflict and violent war-like conditions was also considered.
      The results indicate that Bedouin adolescents in Israel, members of a community
      that has experienced drastic social upheaval, show elevated rates of
      psychopathology. Comparisons of Bedouin adolescents to Palestinian adolescents
      from the West Bank and Gaza suggest that for older adolescents the impact of
      extreme social change on mental health adjustment generally parallels that of
      both chronic social conflict (West Bank) and that of violent war-like conditions
      (Gaza). However, this pattern did not hold for younger adolescents. In the
      Bedouin community, younger adolescents demonstrated significantly less adverse
      impact on adjustment than older adolescents, while such differences did not hold
      in the West Bank and Gaza. Thus the findings suggest a continuum of adverse
      impact of the types of social disorganization examined and a possible interaction
      between type of social disorganization and organismic variables such as age and
      gender.

PMID- 9620164
TI  - Is there a role for physician assistants in community mental health?
AB  - The authors briefly describe the history and development of the medical
      discipline of physician assistants (PAs). A careful review of the literature
      reveals the limited use of PAs in psychiatry, usually only for primary health
      care needs. A model for using PAs as psychiatric assistants is presented,
      including the training required and a description of the clinical and
      administrative functions. The advantages of such a model are multiple. These
      include: 1) more effective and efficient use of the psychiatrist; 2) reduced
      costs of service; 3) increased primary medical screening capability in the CMHC;
      and 4) increased presence of ethnic minorities on the professional staff of the
      CMHC. Disadvantages of the model relate to training and "turf" issues. In view of
      the shortage and dissatisfaction of psychiatrists in CMHC settings, and other
      challenges to the provision of quality mental health care in the community, this
      model should be considered as a logical and positive response to that challenge.
      If the model is valid, then training facilities must make a systematic effort to
      recruit, train, and place psychiatric physician assistants in community agencies.

PMID- 9620165
TI  - Response to "Is there a role for physician assistants in community mental
      health?".

PMID- 9620166
TI  - Expression of Hoxa-1 and Hoxb-7 is regulated by extracellular matrix-dependent
      signals in mammary epithelial cells.
AB  - Homeobox-containing genes encode transcriptional regulators involved in cell fate
      and pattern formation during embryogenesis. Recently, it has become clear that
      their expression in continuously developing adult tissues, as well as in
      tumorigenesis, may be of equal importance. In the mouse mammary gland, expression
      patterns of several homeobox genes suggest a role in epithelial-stromal
      interactions. Because the stroma and the extracellular matrix (ECM) are known to
      influence both functional and morphological development of the mammary gland, we
      asked whether these genes would be expressed postnatally in the gland and also in
      cell lines in culture and whether they could be modulated by ECM. Using a
      polymerase chain reaction-base strategy five members of the Hox gene clusters a
      and b were shown to be expressed in cultured mouse mammary cells. Hoxa-1 and Hoxb
      7 were chosen for further analysis. Hoxb-7 was chosen because it had not been
      described previously in the mammary gland and was modulated at different stages
      of gland development. Hoxa-1 was chosen because it was reported previously to be
      expressed only in mammary tumors, and not in normal glands. We showed that
      culturing the mammary epithelial cell lines SCp2 and CID-9 on a basement membrane
      (BM) that was previously shown to induce a lactational phenotype was necessary to
      turn off Hoxb-7, but a change in cell shape, brought about by culturing the cells
      on an inert substratum such as polyHEMA, was sufficient to downregulate Hoxa-1.
      This is the first report of modulation of homeobox genes by ECM. The results
      provide a rationale for the differential pattern of expression in vivo of Hoxa-1
      and Hoxb-7 during different stages of development. The culture model should
      permit further in-depth analysis of the molecular mechanisms involved in how ECM
      signaling and homeobox genes may interact to bring about tissue organization.

PMID- 9620167
TI  - Transcriptional induction of cyclooxygenase-2 gene by okadaic acid inhibition of
      phosphatase activity in human chondrocytes: co-stimulation of AP-1 and CRE
      nuclear binding proteins.
AB  - The involvement of serine/threonine protein phosphatases in signaling pathways
      that control the expression of the cyclooxygenase-2 (COX-2) gene in human
      chondrocytes was examined. Okadaic acid (OKA), an inhibitor of protein
      phosphatases 1 (PP-1) and 2A (PP-2A), induced a delayed, time-dependent increase
      in the rate of COX-2 gene transcription (runoff assay) resulting in increased
      steady-state mRNA levels and enzyme synthesis. The latter response was dose
      dependent over a narrow range of 1-30 nmol/L with declining expression and
      synthesis of COX-2 at higher concentrations due to cell toxicity. The delayed
      increase in COX-2 mRNA expression was accompanied by the induction of the proto
      oncogenes c-jun, junB, junD, and c-fos (but not FosB or Fra-1). Increased
      phosphorylation of CREB-1/ATF-1 transcription factors was observed beginning at 4
      h and reached a zenith at 8 h. Gel-shift analysis confirmed the up-regulation of
      AP-1 and CRE nuclear binding proteins, though there was little or no OKA-induced
      nuclear protein binding to SP-1, AP-2, NF-kappaB or NF-IL-6 regulatory elements.
      OKA-induced nuclear protein binding to 32P-CRE oligonucleotides was abrogated by
      a pharmacological inhibitor of protein kinase A (PKA), KT-5720; the latter
      compound also inhibited OKA-induced COX-2 enzyme synthesis. Calphostin C (CalC),
      an inhibitor of PKC isoenzymes, had little effect in this regard. Inhibition of
      12P-CRE binding was also observed in the presence of an antibody to CREB-binding
      protein (265-kDa CBP), an integrator and coactivator of cAMP-responsive genes.
      The binding to 32P-CRE was unaffected in the presence of excess radioinert AP-1
      and COX-2 NF-IL-6 oligonucleotides, although a COX-2 CRE-oligo competed very
      efficiently. 32P-AP-1 consensus sequence binding was unaffected by incubation of
      chondrocytes with KT-5720 or CalC, but was dramatically diminished by excess
      radioinert AP-1 and CRE-COX-2 oligos. Supershift analysis in the presence of
      antibodies to c-Jun, c-Fos, JunD, and JunB suggested that AP-1 complexes were
      composed of c-Fos, JunB, and possibly c-Jun. OKA has no effect on total cellular
      PKC activity but caused a delayed time-dependent increase in total PKA activity
      and synthesis. OKA suppressed the activity of the MAP kinases, ERK1/2 in a time
      dependent fashion, suggesting that the Raf-1/MEKK1/MEK1/ERK1,2 cascade was
      compromised by OKA treatment. By contrast, OKA caused a dramatic increase in
      SAPK/JNK expression and activity, indicative of an activation of
      MEKK1/JNKK/SAPK/JNK pathway. OKA stimulated a dose-dependent activation of CAT
      activity using transfected promoter-CAT constructs harboring the regulatory
      elements AP-1 (c-jun promoter) and CRE (CRE-tkCAT). We conclude that in primary
      phenotypically stable human chondrocytes, COX-2 gene expression may be controlled
      by critical phosphatases that interact with phosphorylation dependent (e.g., MAP
      kinases:AP-1, PKA:CREB/ATF) signaling pathways. AP-1 and CREB/ATF families of
      transcription factors may be important substrates for PP-1/PP-2A in human
      chondrocytes.

PMID- 9620168
TI  - Purification of guinea pig YKL40 and modulation of its secretion by cultured
      articular chondrocytes.
AB  - The aim of this study was to purify, characterize, and study the regulation at
      the chondrocyte level of the guinea pig (gp) homologue of human (R) YKL40, a
      putative marker of arthritic disorders. Studying YKL40 in guinea pigs is of
      particular interest, as age-related osteoarthritis develops in this species
      spontaneously. Both N-terminal sequencing and total amino acid composition of
      gpYKL40 purified from the secretion medium of cultured articular chondrocytes
      indicate a high degree of identity with hYKL40. gpYKL40 was found to contain
      complex N-linked carbohydrate, as demonstrated by N-glycosidase F and
      endoglycosidase F digestion. Isoelectric focusing demonstrated the presence of a
      major band at pI 6.7. The secretion of gpYKL40 by confluent articular
      chondrocytes in the extracellular medium was studied by immunoblotting. gpYKL40
      was released by chondrocytes continuously over a 7 day period and did not appear
      to be degraded by proteinases, as its signal intensity in cell-free medium at 37
      degrees C did not decrease with time. Thus, gpYKL40 displays high stability and
      accumulates in extracellular medium without reaching a steady-state level. Among
      the main factors known to regulate cartilage metabolism, IL-1beta, TNF-alpha,
      bFGF, or 1,25(OH)2D3 did not alter the basal level of gpYKL40, and retinoic acid
      had a slight inhibitory effect; TGF-beta and IGF-I and -II dose-dependently and
      inversely modulated this basal level. TGF-beta at 5 ng/ml decreased extracellular
      gpYKL40 2.9-fold, whereas IGF-I and IGF-II at 50 ng/ml increased extracellular
      gpYKL40 3.6- and 3.4-fold, respectively. The present biochemical and biological
      findings give new insights for studying the function of YKL40 in cartilage.

PMID- 9620169
TI  - Arrest of the cell cycle reduces susceptibility of target cells to perforin
      mediated lysis.
AB  - Cytotoxic T lymphocytes secrete a pore-forming cytolysin, perforin, that damages
      membranes of target cells. They also ligate Fas receptors on target cells and
      provoke apoptotic death. A20 (B lymphoma) and P815 (mastocytoma) cell lines were
      examined for their susceptibility to perforin-mediated lysis and to Fas-induced
      apoptosis after blockade of the cell cycle at the G1/S interface. Cells were
      arrested at the G1/S interface by inhibition of DNA synthesis with thymidine or
      aphidicolin. Subsequently, the treated cells were incubated either with CTL
      cytotoxic granules or the Fas-specific monoclonal antibody Jo-2. We show that
      arrest of the cell cycle at the G1/S interface markedly reduced the
      susceptibility of target cells to perforin-mediated lysis. In contrast, growth
      arrest with thymidine or aphidicolin increased susceptibility of A20 and P815
      cells to Fas-mediated apoptosis. Susceptibility to lysis by intact CTLs was not
      affected significantly by blockade of target cells with aphidicolin or thymidine.
      When cells surviving exposure to perforin-containing granules were isolated on
      Ficoll density gradients and cell-cycle profiles were examined by flow cytometry,
      the ratio of G1 to G2 cells increased among the survivors exposed to granules in
      contrast to controls incubated with buffer alone. The data suggest that cells in
      G1 phase of the cell cycle are less susceptible to the perforin pathway than
      cells in G2 and S phases but are more susceptible to the Fas pathway.

PMID- 9620170
TI  - Analysis of the role of Hsp25 phosphorylation reveals the importance of the
      oligomerization state of this small heat shock protein in its protective function
      against TNFalpha- and hydrogen peroxide-induced cell death.
AB  - The role of murine Hsp25 phosphorylation in the protection mediated by this
      protein against TNFalpha- or H2O2-mediated cytotoxicity was investigated in L929
      cell lines expressing wild type (wt-) or nonphosphorylatable (mt-) Hsp25. We show
      that mt-Hsp25, in which the phosphorylation sites, serines 15 and 86, were
      replaced by alanines, is still efficient in decreasing intracellular reactive
      oxygen species levels and in raising glutathione cellular content, leading the
      protective activity of mt-Hsp25 against oxidative stress to be identical to that
      of wt-Hsp25. To independently investigate the role of Hsp25 phosphorylation, we
      blocked TNFalpha-induced phosphorylation of wt-Hsp25 using SB203580, a specific
      inhibitor of the P38 MAP kinase. This treatment did not abolish the protective
      activity of Hsp25 against TNFalpha. The pattern of Hsp25 oligomerization was also
      analyzed, showing mt-Hsp25 to constitutively display large native sizes, as does
      wt-Hsp25 after TNFalpha treatment in the presence of SB203580. Our results,
      therefore, are consistent with the possibility that the hyperaggregated form of
      Hsp25 is responsible for the protective activity against oxidative stress and
      that the phosphorylation of serines 15 and/or 86 by interfering with this
      structural reorganization, may lead to the inactivation of Hsp25 protective
      activity.

PMID- 9620171
TI  - Inhibition of terminal differentiation and matrix calcification in cultured avian
      growth plate chondrocytes by Rous sarcoma virus transformation.
AB  - Endochondral bone formation involves the progression of epiphyseal growth plate
      chondrocytes through a sequence of developmental stages which include
      proliferation, differentiation, hypertrophy, and matrix calcification. To study
      this highly coordinated process, we infected growth plate chondrocytes with Rous
      sarcoma virus (RSV) and studied the effects of RSV transformation on cell
      proliferation, differentiation, matrix synthesis, and mineralization. The RSV
      transformed chondrocytes exhibited a distinct bipolar, fibroblast-like
      morphology, while the mock-infected chondrocytes had a typical polygonal
      morphology. The RSV-transformed chondrocytes actively synthesized extracellular
      matrix proteins consisting mainly of type I collagen and fibronectin. RSV
      transformed cells produced much less type X collagen than was produced by mock
      transformed cells. There also was a significant reduction of proteoglycan levels
      secreted in both the cell-matrix layer and culture media from RSV-transformed
      chondrocytes. RSV-transformed chondrocytes expressed two- to- threefold more
      matrix metalloproteinase, while expressing only one-half to one-third of the
      alkaline phosphatase activity of mock infected cells. Finally, RSV-transformed
      chondrocytes failed to calcify the extracellular matrix, while mock-transformed
      cells deposited high levels of calcium and phosphate into their extracellular
      matrix. These results collectively indicate that RSV transformation disrupts the
      preprogrammed differentiation pattern of growth plate chondrocytes and inhibit
      chondrocyte terminal differentiation and mineralization. They also suggest that
      the expression of extracellular matrix proteins, type II and type X collagens,
      and the cartilage proteoglycans are important for chondrocyte terminal
      differentiation and matrix calcification.

PMID- 9620172
TI  - Upregulation of P-glycoprotein in rat hepatoma rho(o) cells: implications for
      drug-DNA interactions.
AB  - Rat hepatoma cells lacking mitochondrial DNA (rho(o) cells) were used as a model
      system to examine the possible roles of mitochondrial DNA as a target for the DNA
      acting anticancer drug Adriamycin (doxorubicin). The rho(o) cells were 45-fold
      less sensitive to Adriamycin than the parental rho+ cells containing
      mitochondrial DNA. Other non-DNA-acting drugs also exhibited similar behaviour,
      and this was shown to be due to a multidrug resistance (MDR) phenotype in the
      rho(o) cells. This was indicated by confocal microscopy where rho+ cells
      exhibited thirteenfold higher cellular levels of Adriamycin than rho(o) cells.
      Upregulation (tenfold) of P-glycoprotein in rho(o) cells was also confirmed by
      Northern dot blot analysis. Since the MDR phenotype is present in rho(o) cells
      and upregulation of P-glycoprotein is maintained in these cells, rho(o) cells are
      not a good model system for drug-DNA studies (where the drug is susceptible to
      extrusion by P-glycoprotein), and any such results obtained with this system must
      be treated with considerable caution.

PMID- 9620173
TI  - 1alpha,25(OH)2-vitamin D3 signaling in chick enterocytes: enhancement of tyrosine
      phosphorylation and rapid stimulation of mitogen-activated protein (MAP) kinase.
AB  - The steroid hormone 1alpha,25(OH)2-vitamin D3 (1alpha,25(OH)2D3) generates
      biological responses in intestinal and other cells via both genomic and rapid,
      nongenomic signal transduction pathways. We examined the hypothesis that
      1alpha,25(OH)2D3 action in chick enterocytes may be linked to pathways involving
      tyrosine phosphorylation. Brief exposure of isolated chick enterocytes to
      1alpha,25(OH)2D3 demonstrated increased tyrosine phosphorylation of several
      cellular proteins (antiphosphotyrosine immunoblots of whole cell lysates) with
      prominent bands at 42-44, 55-60, and 105-120 Kda. The 42-44 Kda bands comigrated
      with mitogen-activated protein (MAP) kinase (immunoblotting with anti-MAP kinase
      antibody) The response occurred within 30 s, peaked at 1 min, and was dose
      dependent (0.01-10 nM), with maximal stimulation at 1 nM (three- to fivefold).
      This effect was specific for 1alpha,25(OH)2D3 since its metabolic precursors
      25(OH)D3 and vitamin D3 did not increase MAP kinase tyrosine phosphorylation. The
      tyrosine kinase inhibitor, genistein, blocked 1alpha,25(OH)2D3-induced tyrosine
      phosphorylation of MAP kinase, while staurosporine, a PKC inhibitor, attenuated
      the hormone's effects by 30%. We have evaluated the ability of 1alpha,25(OH)2D3
      analogs, which have complete flexibility around the 6,7 carbon-carbon bond (6F)
      or which are locked in either the 6-s-cis (6C) or the 6-s-trans (6T) shape(s), to
      activate MAP kinase. Thus, two 6F and one 6C analog stimulated while one 6T
      analog did not stimulate MAP kinase tyrosine phosphorylation. In addition,
      1beta,25(OH)2D3, a known antagonist of 1alpha,25(OH)2D3-mediated rapid responses,
      blocked the hormone effects on MAP kinase. We conclude that 1alpha,25(OH)2D3 and
      analogs which can achieve the 6-s-cis shape (6F and 6C) can increase tyrosine
      phosphorylation and activation of MAP kinase in chick enterocytes.

PMID- 9620174
TI  - Effects of a water-soluble extract of Cordyceps sinensis on steroidogenesis and
      capsular morphology of lipid droplets in cultured rat adrenocortical cells.
AB  - Cordyceps sinensis contains a factor that stimulates corticosteroid production in
      the animal model. However, it is not known whether this drug acts directly on the
      adrenal glands or indirectly via the hypothalamus-pituitary axis. In the present
      study, we used primary rat adrenal cell cultures to investigate the
      pharmacological function of a water-soluble extract of Cordyceps sinensis (CS)
      and the signaling pathway involved. Radioimmunoassay of corticosterone indicated
      that the amount of corticosterone produced by adrenal cells is increased in a
      positively dose-dependent manner by CS, reaching a maximum at 25 microg/ml. This
      stimulating effect was seen 1 h after CS treatment and was maintained for up to
      24 h. Concomitantly, the lipid droplets in these cells became small and fewer in
      number. Immunostaining with a monoclonal antibody, A2, a specific marker for the
      lipid droplet capsule, demonstrated that detachment of the capsule from the lipid
      droplet occurs in response to CS application and that the period required for
      decapsulation is inversely related to the concentration of CS applied. The
      mechanism of CS-induced steroidogenesis is apparently different from that for
      ACTH, since intracellular cAMP levels were not increased in CS-treated cells.
      However, combined application with calphostin C, a PKC inhibitor, completely
      blocked the effect of CS on steroidogenesis, suggesting that activation of PKC
      may be responsible for the CS-induced steroidogenesis.

PMID- 9620175
TI  - Nucleolar targeting of 5S RNA in Xenopus laevis oocytes: somatic-type nucleotide
      substitutions enhance nucleolar localization.
AB  - In Xenopus laevis oocytes, 5S RNA is stored in the cytoplasm until
      vitellogenesis, at which time it is imported into the nucleus and targeted to
      nucleoli for ribosome assembly. This article shows that throughout oogenesis
      there is a pool of nuclear 5S RNA which is not nucleolar-associated. This
      distribution reflects that of oocyte-type 5S RNA, which is the major 5S RNA
      species in oocytes; only small amounts of somatic-type, which differs by six
      nucleotides, are synthesized. Indeed, 32P-labeled oocyte-type 5S RNA showed a
      degree of nucleolar localization similar to endogenous 5S RNA (33%) after
      microinjection. In contrast, 32P-labeled somatic-type 5S RNA showed significantly
      enhanced localization, whereby 70% of nuclear RNA was associated with nucleoli. A
      chimeric RNA molecule containing only one somatic-specific nucleotide
      substitution also showed enhanced localization, in addition to other somatic
      specific phenotypes, including enhanced nuclear import and ribosome
      incorporation. The distribution of 35S-labeled ribosomal protein L5 was similar
      to that of oocyte-type 5S RNA, even when preassembled with somatic-type 5S RNA.
      The distribution of a series of 5S RNA mutants was also analyzed. These mutants
      showed various degrees of localization, suggesting that the efficiency of
      nucleolar targeting can be influenced by many discrete regions of the 5S RNA
      molecule.

PMID- 9620177
TI  - Fracture dislocations of the proximal interphalangeal joint.

PMID- 9620176
TI  - Expression of second messenger- and cyclin-dependent protein kinases during
      postnatal development of rat heart.
AB  - During early postnatal development, cardiomyocytes, which comprise about 80% of
      ventricular mass and volume, become phenotypically developed to facilitate their
      contractile functions and terminally differentiated to grow only in size but not
      in cell number. These changes are due to the expression of contractile proteins
      as well as the regulation of intracellular signal transduction proteins. In this
      study, the expression patterns of several protein kinases involved in various
      cardiac functions and cell-cycle control were analyzed by Western blotting of
      ventricular extracts from 1-, 10-, 20-, 50-, and 365-day-old rats. The expression
      level of cAMP-dependent protein kinase was slightly decreased (20%) over the
      first year, whereas no change was detected in cGMP-dependent protein kinase I.
      Calmodulin-dependent protein kinase II, which is involved in Ca2+ uptake into the
      sarcoplasmic reticulum, was increased as much as ten-fold. To the contrary, the
      expressions of protein kinase C-alpha and iota declined 77% with age. Cyclin
      dependent protein kinases (CDKs) such as CDK1, CDK2, CDK4, and CDK5, which are
      required for cell-cycle progression, abruptly declined to almost undetectable
      levels after 10-20 days of age. In contrast, other CDK-related kinases, such as
      CDK8 or Kkialre, did not change significantly or increased up to 50% with age,
      respectively. Protein kinases implicated in CDK regulation such as CDK7 and Wee1
      were either slightly increased in expression or did not change significantly. All
      of the proteins that were detected in ventricular extracts were also identified
      in isolated cardiac myocytes in equivalent amounts and analyzed for their
      relative expression in ten other adult rat tissues.

PMID- 9620178
TI  - Intrafocal (Kapandji) pinning of distal radius fractures with and without
      external fixation.
AB  - Seventy-three patients were treated with either intrafocal pinning (Kapandji
      technique) alone or in combination with external fixation between 1988 and 1993
      for extra-articular fractures of the distal radius (with or without a
      nondisplaced extension into the radiocarpal articular surface) with inadequate
      alignment after initial closed reduction. Sixty-one patients were available for
      follow-up examination at an average of 34 months (range, 24-71 months). The
      average age was 52 years (range, 16-84 years). Thirty-three of the patients were
      female. The patients all had dorsally displaced extra-articular fractures,
      although 56% had a nondisplaced extension of the fracture into the radiocarpal
      joint and 46% had a nondisplaced fracture extending into the distal radioulnar
      joint. The patients were separated into groups based on age, degree of
      comminution, and whether external fixation was also used. In the older patients,
      range of motion, grip strength, and pain relief were significantly better when
      external fixation was used, even when only 1 cortex of the radius demonstrated
      comminution. In the younger patients, good results in terms of range of motion,
      grip strength, and pain relief were obtained when percutaneous intrafocal pins
      were used alone in patients with comminution of only 1 surface of the radius
      (<50% of the metaphyseal diameter). When > or = 2 sides of the radial metaphysis
      were comminuted, the patients with external fixation had better results than
      those without external fixation. Although the correction of palmar tilt and
      radial tilt did result in better functional results, the restoration of radial
      length had the most significant effect on range of motion and grip strength.

PMID- 9620179
TI  - Biomechanical analysis of capitate shortening with capitate hamate fusion in the
      treatment of Kienbock's disease.
AB  - The biomechanical effects of surgical treatment options for Kienbock's disease
      have been compared. However, no study has included a direct analysis of capitate
      shortening along with capitate-hamate fusion (CSCHF). To investigate the
      biomechanical effects of CSCHF, a cadaver model of the upper extremity was used
      to determine radiocarpal articular pressure changes resulting from this procedure
      using pressure-sensitive film. Ten specimens were tested by placing each in an
      apparatus that applied load across the radiocarpal joint through the wrist flexor
      and extensor tendons. Testing was performed in 3 wrist positions (ulnar
      deviation, radial deviation, and neutral) combined with 3 forearm positions
      (pronation, supination, and neutral) and neutral flexion/extension.
      Radioscaphoid, radiolunate, and mean contact pressures in the entire radiocarpal
      joint were determined for each of the 9 wrist positions, both intact and after
      surgery. The radioscaphoid mean pressure increased in 6 of 9 positions and was
      unchanged in 3 positions. The radiolunate mean pressure decreased in 9 of 9
      positions. The radiocarpal mean pressure increased in 2 of 9 positions and was
      unchanged in 7 positions. These data suggests that CSCHF increases radioscaphoid
      mean pressure, decreases radiolunate mean pressure, and has little effect on
      radiocarpal mean pressure.

PMID- 9620180
TI  - Temporary internal fixation of the scaphotrapezio-trapezoidal joint for the
      treatment of Kienbock's disease: a preliminary study.
AB  - Temporary scaphotrapezio-trapezoidal (STT) fixation with Kirschner wires (K
      wires) has been used in the treatment of 16 cases of Kienbock's disease since
      1988. Twelve of these cases with a follow-up of at least 1 year were reviewed.
      Eight patients were women and 4 were men and the average age at the time of
      surgery was 44 years (range, 20-67 years). Five cases were treated with temporary
      STT fixation and vascular bundle implantation (group V), and 7 cases were treated
      with temporary STT fixation and tendon roll implantation (group T). K-wires were
      removed between 16 and 26 weeks after surgery (average, 18.6 weeks) in group V,
      and between 8 and 13 weeks (average, 9.7 weeks) in group T. The follow-up periods
      ranged from 12 to 92 months (average, 38 months). Postoperative wrist pain
      disappeared in 7 cases and decreased in 5. The postoperative arc of wrist flexion
      and extension increased from 97 degrees to 108 degrees in group V and from 85
      degrees to 103 degrees in group T. Grip strength improved from 22.2 to 30.6 kg in
      group V and from 11.4 kg to 17.7 kg in group T. X-ray evaluation revealed that
      the mean carpal height ratio was 0.488 before surgery, 0.489 during STT fixation,
      and 0.480 at the final follow-up. The carpal height decreased in 3 cases (2 in
      group V and 1 in group T). The postoperative radioscaphoid angle improved in all
      cases during K-wire insertion and regressed after removal of the K-wire,
      eventually showing a decrease in 4 cases, an increase in 3 cases, and no change
      in 5 cases.

PMID- 9620181
TI  - Temporary scapho-trapezoidal joint fixation for Kienbock's disease in a 12-year
      old girl: a case report.
AB  - Temporary scapho-trapezoidal joint fixation with Kirschner wires was performed
      for stage IIIB Kienbock's disease in a 12-year-old girl. Preoperative evaluation
      with radiographs and magnetic resonance imaging confirmed the diagnosis. After 4
      months of fixation, wrist range of motion was improved and pain was decreased.
      Postoperative magnetic resonance imaging revealed revascularization and fracture
      healing. Temporary scapho-trapezoidal fixation may be useful in the treatment of
      selected cases of Kienbock's disease in children.

PMID- 9620182
TI  - Force transmission through the wrist joint in Kienbock's disease: a two
      dimensional theoretical study.
AB  - This study quantifies the changes in force and pressure distributions across the
      wrist joint in different stages of Kienbock's disease using a 2-dimensional
      computer simulation model. Twenty-four cases classified as Lichtman's stage II,
      IIIA, or IIIB (8 cases in each category) were analyzed using the rigid body
      spring model technique. A 2-dimensional model in the posteroanterior plane of the
      wrist was loaded through the metacarpals under a total force of 142 N. The joint
      forces, peak pressures, and ligament tensions calculated on the involved side
      were normalized against the contralateral normal side values of the same patient.
      The results demonstrated that significant changes of the force transmission
      across the wrist joint occurred only from stage IIIA to IIIB, in which scaphoid
      rotation was prominent. On the basis of this study, scaphoid rotation plays an
      important role in affecting the wrist joint contact pressure distribution. This
      may be responsible for the progression of Kienbock's disease.

PMID- 9620183
TI  - Lunotriquetral ligament properties: a comparison of three anatomic subregions.
AB  - The physical attributes of 3 subregions of the lunotriquetral ligament were
      tested in a computer-controlled multiaxis testing machine using 12 specimens.
      This allowed measurement of forces, moments, and displacements when ligaments
      were subjected to distraction, dorsopalmar translation, proximal-distal
      translation with a 20 N limit, and rotation with a 0.5 Nm limit. After an intact
      test run, selected subregions were cut randomly. Together with an additional 12
      bone-ligament-bone complexes, specimens were tested to failure with
      servohydraulic load at 5 mm/s. The palmar subregion was thickest (2.3 +/- 0.3
      mm), the dorsal and proximal progressively less. Intact rotational displacement
      was 35 degrees +/- 5.1 degrees, dorsopalmar displacement was 1.6 +/- 0.4 mm and
      1.2 +/- 0.5 mm, respectively, proximal-distal displacement was 1.8 +/- 0.5 mm and
      1.3 +/- 0.5 mm, respectively, and distractional displacement was 0.3 +/- 0.1 mm.
      The dorsal subregion provided 62.3% +/- 27.1% of the rotational resistance. The
      palmar subregion resisted 67.3% +/- 14.1% of palmar translation, while with
      dorsal translation both regions resisted equally. Rotational displacement
      increased 15.3 degrees +/- 5.6 degrees after dorsal subregion sectioning. The
      palmar component failure force was 301 +/- 36 N; the dorsal, 121 +/- 42 N; and
      the proximal, 64 +/- 14 N.

PMID- 9620184
TI  - The lunotriquetral joint: kinematic effects of sequential ligament sectioning,
      ligament repair, and arthrodesis.
AB  - This experiment was conducted to study the effects of sequential sectioning of
      the ligaments of the lunotriquetral (LT) joint and the effects of simulated
      repair or arthodesis on kinematics of the wrist joint using an x-ray
      stereophotogrammetric technique. A 3-dimensional coordinate software program
      calculated relative motion between bodies as screw axis displacement and rotation
      about each axis. Sectioning of the proximal and dorsal component of the LT
      ligament had little effect on carpal kinematics, but sectioning of the proximal
      and palmar components of the ligament resulted in flexion of both the lunate and
      triquetrum, producing a volar intercalated segment instability (VISI) pattern.
      The triquetrum supinated away from the lunate after sectioning of the entire LT
      ligament. Greater VISI occurred after sectioning the dorsal radiotriquetral and
      scaphotriquetral ligaments. Progressive destabilization of the LT joint results
      in increasing kinematic alterations; however, these may not exactly mimic the
      clinical situation. Moving the wrist through 1,000 cycles increased the
      instability. Dorsal repair of the LT ligament realigned the lunate and
      triquetrum, and LT fusion corrected triquetral supination. The latter, however,
      resulted in overcorrection into extension, which prevented a full wrist
      extension. The repair used may be insufficient to restore the palmar ligamentous
      integrity. Lunotriquetral arthodesis was difficult to simulate, providing some
      insight into the cause of clinical nonunions. Severe VISI is not correctable by
      repair or arthrodesis and requires further study using reconstructive procedures
      not discussed here.

PMID- 9620185
TI  - High-speed, three-dimensional kinematic analysis of the normal wrist.
AB  - Carpal kinematics during a wrist flexion/extension motion using high-speed
      videodata acquisition was investigated. A cadaver forearm was stabilized,
      allowing unconstrained excursion of the wrist for passive range of motion (ROM).
      The extensor and flexor pairs of the wrist were looped together and a 1-lb weight
      was attached to each pair, simulating synergistic muscle tension. Capitate/radius
      and third metacarpal/radius angles were calculated to determine which measurement
      would be best for determining global wrist angle. The average difference in
      capitate/radius and third metacarpal/radius angles at each respective
      flexion/extension wrist angle for all wrists was 1.1 degrees +/- 1.6 degrees (the
      maximum difference was 4 degrees). Hence, the capitate-third metacarpal joint can
      be considered rigid. Capitate/lunate motion as described by capitate-radius Euler
      angles ranged from -16.9 to 23.5 with total capitate/lunate motion of 40.5 (35%)
      in the 114 degrees total global wrist ROM measured. Radius/lunate motion as
      described by lunate-radius angle ranged from -8.2 to 48.4 with total
      radius/lunate motion of 56.5 (49%) in the 114 degrees total global wrist ROM
      measured. During global wrist motion, the radiolunate joint contributes more
      motion in flexion than the capitolunate joint and the capitolunate joint
      contributes more motion in extension than the radiolunate joint. The
      instantaneous screw axes (ISAs) were calculated for each third metacarpal
      position with respect to the radius. The average distance difference between ISAs
      for the 4 wrists tested was -1.23 +/- 14.97 pixels. The maximum distance was
      56.51 pixels and the minimum was -24.09 pixels. This new combination of motion
      analysis and 3-dimensional reconstructions of computed tomography images affords
      a high-speed, dynamic analysis of kinematics. It shows that during wrist
      flexion/extension, normal carpal kinematics does not have an ISA fixed in or
      limited to the capitate. In addition, the ISA data provide evidence that
      translational motion is a real and measurable component of normal carpal motion.
      These findings alter the understanding of carpal kinematics obtained from the
      results of previous studies which suggested that the center of rotation was fixed
      in the capitate.

PMID- 9620186
TI  - Topography of the osteoarthritic thumb carpometacarpal joint and its variations
      with regard to gender, age, site, and osteoarthritic stage.
AB  - The articular topography of 46 osteoarthritic thumb carpometacarpal joints was
      quantitatively analyzed, as well as variations with regard to gender, age, site,
      and anatomic osteoarthritic stage. It was found that for osteoarthritic thumb
      carpometacarpal joints, (1) the opposing articular surfaces of elder and severely
      degenerated joints are more congruent than those of middle-aged and minimally or
      moderately degenerated joints, although the articular contact area is not
      significantly different when accounting for thinning of the cartilage layer with
      age or disease; (2) significant changes in joint topography due to osteoarthritis
      only occur in severely degenerated joints; (3) joints in women are less
      congruent, have smaller contact areas, and are likely to experience higher
      contact stresses than joints in men for similar activities of daily living that
      involve similar joint loads; and (4) osteoarthritic changes are less severe on
      the dorsoulnar aspect of the trapezium and the dorsal aspect of the metacarpal,
      which are known to be low load-bearing regions.

PMID- 9620187
TI  - Tensile properties of the neurorrhaphy site in the rat sciatic nerve.
AB  - Forty-three epineurial rat sciatic neurorrhaphies were performed to gain insight
      into the duration necessary to protect a nerve repair. By killing animals at
      varying intervals after neurorrhaphy and harvesting the sciatic nerves, we
      investigated the timing of neurorrhaphy site tensile property recovery. There
      were 9 normal control nerves. No nerves ruptured after repair, even though the
      operated legs were not immobilized. Ultimate and maximal simulated in situ loads
      and elongations were measured, and stresses and strains were calculated from
      mechanical testing. Sixty-four percent of normal ultimate stress was gained
      during the first week after neurorrhaphy, with no significant increase for 10 to
      12 weeks. Ultimate strains for control and repaired nerves for all time intervals
      ranged from 14.2% +/- 1.8% to 26.0% +/- 3.9%. Maximal simulated in situ stress
      and strain remained in the toe region of the stress versus strain curve, implying
      that no nerves ruptured because ultimate stress and strain were never approached.
      Caution must be exercised in extrapolating these data to the human clinical
      situation.

PMID- 9620188
TI  - Functional results of low median and ulnar nerve repair with intraneural
      fascicular dissection and electrical fascicular orientation.
AB  - Twenty-eight low median nerve injuries and 23 low ulnar nerve injuries were
      repaired using intraneural fascicular dissection and electrical fascicular
      orientation. Eleven freshly lacerated nerves were seen within 48 hours after
      injury; 40 nerve lacerations were chronic. Fascicular orientation between sensory
      and motor fascicles at the proximal nerve end could be accurately differentiated
      in 47 nerves (92%) independent of whether it was acute or chronic. At the distal
      nerve end in fresh lacerations, the motor fascicles could be determined
      conclusively by muscle contraction with sequential electrical stimulation of the
      fascicles. In chronic nerve lacerations, the distal fascicles could be estimated
      anatomically after internal neurolysis. After fascicular orientation, nerves were
      repaired with end-to-end group fascicular suture or interfascicular sural nerve
      grafting. Twenty-four nerves repaired with end-to-end suture and 13 nerves
      repaired with nerve grafting were monitored more than 25 months. Satisfactory
      sensory results (i.e., S3+ or S4 functions) were obtained in 29 nerves (78%) and
      M4 or M5 motor functions were achieved in 29 nerves (78%). There were no patients
      who needed additional tendon transfers to reconstruct thumb opposition or to
      correct claw finger deformity. These results suggest that low median or ulnar
      nerve lacerations, whether acute or chronic, partial or complete, may be
      successfully repaired with the aid of electrical fascicular orientation with or
      without intraneural fascicular dissection.

PMID- 9620189
TI  - Cubital tunnel release with medial epicondylectomy factors influencing the
      outcome.
AB  - From 347 cases of documented cubital tunnel syndrome, 160 required cubital tunnel
      release and medial epicondylectomy over a 10-year period and were considered for
      this retrospective study. These patients were monitored for 3 years after
      surgery. According to the modified scale of McGowan, 86% of patients were
      considered stage II. Eighty-one percent of the patients were symptom free, and
      96% of the patients improved by 1 Wilson and Krout grade following surgery. We
      considered return of symptoms 3 months or longer after surgery as recurrence;
      there were 21 recurrences. There was no correlation between recurrence and limb
      dominance, patient age at the time of surgery, or length of preoperative
      conservative treatment. Of the patients with recurrences, 44% were in their
      fourth decade of life. The rate of recurrence in females (18%) was almost twice
      that in males (10%). The rate of recurrence was increased twofold when the
      patient did not return to work within 3 months. When concomitant ipsilateral
      carpal tunnel was present (44%), the recurrence rate was 17% compared with 9% in
      those without carpal tunnel syndrome. The recurrence rate was 20% when
      ipsilateral thoracic outlet syndrome was present compared with 9% in patients
      without other ipsilateral maladies. Therefore, higher recurrence rates should be
      anticipated in female patients, in patients with concomitant ipsilateral thoracic
      outlet syndrome and/or carpal tunnel syndrome, in patients in their third or
      fourth decade of life, or in patients not returning to work within 3 months after
      surgery.

PMID- 9620190
TI  - A modified surgical procedure for cubital tunnel syndrome: partial medial
      epicondylectomy.
AB  - Cubital tunnel release with partial medial epicondylectomy was performed in 32
      patients with cubital tunnel syndrome unresponsive to conservative management.
      Twenty-seven patients were available for examination an average follow-up of 13
      months. Ninety-three percent were subjectively improved, with results being
      excellent in 8, good in 10, fair in 8, and poor in 1. Regression analyses showed
      a statistically significant correlation between outcome and slow ulnar nerve
      conduction velocity across the elbow, abnormal preoperative 2-point
      discrimination, abnormal preoperative terminal sensory latency of the ulnar
      nerve, and abnormal preoperative electromyographic studies. The results suggest
      that the procedure is an acceptable alternative for treatment of cubital tunnel
      syndrome.

PMID- 9620191
TI  - Use of the medial intermuscular septum as a fascial sling during anterior
      transposition of the ulnar nerve.
AB  - A new technique using the released medial intramuscular septum as a fascial or
      fasciodermal sling to prevent posterior subluxation of the ulnar nerve following
      subcutaneous transposition is described. The technique is simple and prevents
      subluxation, yet it still allows free excursion of the ulnar nerve and
      postoperative rehabilitation is begun immediately.

PMID- 9620192
TI  - Continuous passive motion following metacarpophalangeal joint arthroplasty.
AB  - To determine whether a postoperative rehabilitation protocol incorporating
      continuous passive motion would increase the total range of motion obtained 6
      months following silicone interposition arthroplasty of the metacarpophalangeal
      joints in patients with rheumatoid arthritis, a prospective trial randomizing
      patients to receive either continuous passive motion or the standard dynamic
      splint protocol (modified Madden protocol) was undertaken. Fifteen hands (60
      joints) were treated with the modified Madden protocol and 10 hands (40 joints)
      had continuous passive motion. The mean 6-month postoperative range of motion was
      7 degrees in the modified Madden cohort compared with 39 degrees in the
      continuous passive motion cohort, representing an improvement of 22 degrees in
      the modified Madden cohort compared with an improvement of only 5 degrees in the
      continuous passive motion cohort. Residual ulnar deviation 8 degrees vs 12
      degrees and grip strength (2.3 kgf v 3.7 kgf) were both lower in the continuous
      passive motion cohort. Incorporation of the continuous passive motion machine in
      the postoperative rehabilitation protocol does not offer sufficient advantages to
      justify the added costs.

PMID- 9620193
TI  - Mechanoreceptors in the human elbow ligaments.
AB  - The medial, annular, and lateral elbow ligaments from 6 fresh human cadavers were
      dissected from origin to insertion, stained, and examined with a light microscope
      to determine the existence of mechanoreceptors. It was shown that the anterior,
      posterior, and transverse medial ligaments as well as the annular and radial
      collateral ligaments were endowed with mechanoreceptors. The mechanoreceptors
      consisted of Golgi organs, Ruffini terminals, Pacinian corpuscles, and free nerve
      endings. The mechanoreceptors were distributed evenly throughout the annular and
      transverse medial ligament, but with increased density toward the origin and
      distal insertions in the radial, posterior, and anterior medial ligaments. It was
      concluded that the elbow ligaments may provide significant sensory function to
      the elbow joint, in addition to being its major mechanical restraints.

PMID- 9620194
TI  - Metacarpal shaft fractures: the effect of shortening on the extensor tendon
      mechanism.
AB  - Spiral and oblique metacarpal shaft fractures frequently develop shortening
      through the fracture site. The acceptable amount of fracture shortening has not
      been well established. The goal of this study was to elucidate the acceptable
      limits of metacarpal shaft fracture shortening in a cadaver model by assessing
      the magnitude of the metacarpophalangeal (MCP) joint extensor lag produced. Nine
      fresh-frozen cadaver hands were used to create a metacarpal shaft fracture model
      in the second and fifth metacarpal bones. Sequential shortening up to 10 mm in 2
      mm increments was performed. The results revealed an average of 7 degrees of
      extensor lag at the MCP joint produced for every 2 mm of metacarpal shortening.
      The capacity of the MCP joint for active hyperextension may compensate for the
      extensor lag produced by metacarpal shortening in the clinical setting.

PMID- 9620195
TI  - Closed rupture of the deep transverse metacarpal ligament: diagnosis and
      management.
AB  - Closed rupture of the deep transverse metacarpal ligament (DTML) is an unusual
      injury. We have managed 2 patients with closed rupture of the DTML between the
      ring and small fingers resulting from crush injuries to the hand. Both patients
      presented with painful ulnar deviation of the small finger with extension. The
      diagnosis was confirmed by exploration through a volar incision. Repair of the
      ligament with use of the adjacent A1 pulleys to butress the repair was successful
      in both patients and restored a painless finger flexion-extension arc. Closed
      rupture of the DTML can be confused with a metacarpophalangeal joint collateral
      ligament rupture due to the characteristic deviation of the small finger.

PMID- 9620196
TI  - Divergent dislocation of the fourth and fifth carpometacarpal joints.
AB  - A case of divergent dislocation of the fourth and fifth carpometacarpal joints is
      reported. The injury resulted from a high-energy trauma and was treated by closed
      reduction and cast immobilization for 4 weeks. Evaluation at the 26-month follow
      up visit showed good radiographic and functional results.

PMID- 9620197
TI  - Physeal growth arrest of the distal phalanx of the thumb in an adolescent
      pianist: a case report.
AB  - A case of premature closure of the distal phalanx growth plate of the thumb is
      reported in an adolescent, presumably caused by accumulated repetitive trauma
      incurred during years of piano playing. The injury may be analogous to overuse
      injury to certain growth plates reported in child and adolescent athletes. Upper
      extremity problems in musicians due to the unusual and excessive demands of
      playing an instrument are discussed.

PMID- 9620198
TI  - Ulnar collateral ligament tear with concomitant extensor pollicis brevis and
      extensor pollicis longus disruptions: a case report.
AB  - A patient with a tear of the thumb ulnar collateral ligament and simultaneous
      extensor pollicis brevis and extensor pollicis longus disruptions is reported. No
      report of a similar constellation of injuries was found in the literature.

PMID- 9620199
TI  - Vascularized bone graft from the second metacarpal to the thumb: a case report.
AB  - Bony pedicled grafts arising from the second metacarpal have been described,
      mainly for the treatment of recurrent pseudarthrosis of the scaphoid. The
      clinical use of this graft has been extended for the management of nonunion of
      the proximal phalanx of the thumb.

PMID- 9620200
TI  - Chronic lymphocytic leukemia presenting as pyogenic arthritis of the proximal
      interphalangeal joint.
AB  - A 66-year-old woman was seen and treated for a chronic lymphocystic leukemic
      infiltrate of a proximal interphalangeal joint, which presented with clinical and
      radiologic signs consistent with a pyogenic arthritis.

PMID- 9620201
TI  - Use of a subcutaneous pedicle ulnar flap to cover skin defects around the wrist.
AB  - A subcutaneous pedicle ulnar flap used to cover a skin defect around the wrist is
      reported. Unlike the standard ulnar flap, which is isolated around the dorsal
      branch of the ulnar artery and its associated veins, this flap is based on the
      ascending branch of the dorsal branch of the ulnar artery more proximally to
      obtain a longer vascular pedicle. A subcutaneous pedicle flap that contained the
      ascending branch, its associated veins, and a superficial vein was obtained. The
      disadvantages of the standard ulnar flap can be overcome by this design, which
      provides greater mobility, preserves the healthy skin between the rotation point
      and the defect, and eliminates contour abnormalities.

PMID- 9620202
TI  - Subungual melanoma.

PMID- 9620203
TI  - Immune response to recombinant visna virus Gag and Env precursor proteins
      synthesized in insect cells.
AB  - Two different recombinant visna virus (VV) gag-baculoviruses were constructed for
      the expression of precursor VV Gag in insect cells. Both recombinant Gag viruses
      expressed proteins migrating on SDS PAGE at the predicted rate for VV Gag
      precursor, Pr50gag. However, differences were seen in the morphology of the virus
      like particles produced. Monoclonal antibody directed against the VV Gag capsid
      protein (p25) and sera from sheep infected with ovine lentiviruses reacted to
      both 50-kDa proteins. A recombinant VV env-baculovirus was constructed,
      substituting sequences encoding the signal peptide of VV Env with the murine IFN
      gamma analogue. Sera from ovine lentivirus infected sheep reacted in immunoblots
      with two proteins of approximately 100 and 200 kDa found in the plasma membrane
      of insect cells infected with env-recombinant virus. Sheep immunized with either
      the recombinant Gag or the Env proteins developed high antibody titers to VV in
      ELISA. The serum of sheep and ascitic fluid of mice immunized with the
      recombinant Gag reacted with native Pr50gag and the processed Gag proteins in
      immunoblots, whereas serum of the recombinant Env immunized sheep reacted with VV
      gp135 and a putative oligomer of gp135. The immunized sheep responded
      specifically to visna virus by lymphocyte proliferation in vitro.

PMID- 9620204
TI  - Cellular membrane factors are the major determinants of porcine reproductive and
      respiratory syndrome virus tropism.
AB  - The mechanism that restricts porcine reproductive and respiratory syndrome virus
      (PRRSV) replication in a variety of cell-lines has been investigated in this
      study. Using a virus binding assay, it was found that PRRSV could not bind to
      most cell-lines tested. However, vero cells, which are non-permissive to PRRSV
      infection, were able to bind and internalize a virus almost as efficiently as the
      permissive cell-line MARC-145. In addition, MARC-145 and vero cells internalized
      PRRSV in an infectious form, indicating that virus entry occurred by receptor
      mediated endocytosis. Polyethylene glycol (PEG)-mediated fusion of virus with
      cells induced the production of infectious virus from vero and MARC-145, but not
      from the others cells tested. Infectious virus was also recovered from vero and
      several other non-permissive cell types after transfection of viral RNA,
      indicating that the viral genome is infectious per se. Thus, absence of PRRSV
      binding to cells might be one major determinant of PRRSV cell tropism. However,
      because vero cells restricted PRRSV replication following virus binding and
      internalization but prior to RNA replication, it is possible that multiple viral
      and cellular components might be involved in allowing PRRSV replication on cells.

PMID- 9620205
TI  - Fusion of influenza virus with the endosomal membrane is inhibited by monoclonal
      antibodies to defined epitopes on the hemagglutinin.
AB  - Epitopes on the hemagglutinin (HA) of A/seal/Massachusetts/1/80 (H7N7) influenza
      virus were mapped by genetic analysis of variants selected with monoclonal
      antibodies (MAbs). Electron microscopic studies demonstrated that the sites and
      the directions to which hemagglutination-inhibiting (HI) MAbs and non-HI MAbs
      bound were different on the HA molecule. Morphological analysis revealed that HI
      MAbs blocked attachment of the virus to the cells, while non-HI MAbs did not.
      Virus particles bound with non-HI MAbs were then found in the intracellular
      vacuoles. Together with the electron microscopic findings, a fluorescence
      dequenching assay indicated that non-HI MAbs inhibited the fusion of virus with
      the intracellular vacuolar membrane. It was thus shown that non-HI neutralizing
      MAbs did not inhibit attachment of the virus to the host cell receptor, but
      inhibited the fusion step in intracellular vacuoles. The results support the
      hypothesis that anti-HA MAbs which lack HI activity neutralize viral infectivity
      by interfering with the low pH-induced conformational change in the HA molecule,
      resulting in inhibition of the fusion step in the viral replication process
      (Kida, H., Yoden, S., Kuwabara, M., Yanagawa, R., 1985. Interference with a
      conformational change in the HA molecule of influenza virus by antibodies as a
      possible neutralization mechanism. Vaccine 3, 219-222).

PMID- 9620206
TI  - Expression of recombinant hepatitis C virus non-structural protein 5B in
      Escherichia coli.
AB  - The hepatitis C virus (HCV) represents a major public health problem that can
      produce liver failure and hepatocellular carcinoma in chronically infected
      patients. Our goal was to express the HCV non-structural protein 5B (NS5B)
      protein of HCV genotype 1a in Escherichia coli and initiate studies of its role
      in HCV genomic replication. In this report we demonstrate that a recombinant NS5B
      protein with an amino terminal sequence of ASMSYSWTG has RNA-dependent RNA
      polymerase (RDRP) activity. This recombinant enzyme was active in poly(U)
      polymerase assays and produced template-sized RNA products when globin mRNA was
      used as a template. The polymerase activity of recombinant NS5B was primer
      dependent and was active for at least 60 min of incubation at 30 degrees C.
      Deletion of the carboxyl terminal region of HCV NS5B resulted in a loss of RDRP
      activity indicating that the enzymatic activity observed was due to the full
      length recombinant enzyme. Recombinant NS5B (RDRP) should assist in understanding
      the mechanism of HCV replication and the identification of specific enzyme
      inhibitors.

PMID- 9620207
TI  - Genomic organization of the canine herpesvirus US region.
AB  - Canine herpesvirus (CHV) is an alpha-herpesvirus of limited pathogenicity in
      healthy adult dogs and infectivity of the virus appears to be largely limited to
      cells of canine origin. CHV's low virulence and species specificity make it an
      attractive candidate for a recombinant vaccine vector to protect dogs against a
      variety of pathogens. As part of the analysis of the CHV genome, the authors
      determined the complete nucleotide sequence of the CHV US region as well as
      portions of the flanking inverted repeats. Seven full open reading frames (ORFs)
      encoding proteins larger than 100 amino acids were identified within, or
      partially within the CHV US: cUS2, cUS3, cUS4, cUS6, cUS7, cUS8 and cUS9; which
      are homologs of the herpes simplex virus type-1 US2; protein kinase; gG, gD, gI,
      gE; and US9 genes, respectively. An eighth ORF was identified in the inverted
      repeat region, cIR6, a homolog of the equine herpesvirus type-1 IR6 gene. The
      authors identified and mapped most of the major transcripts for the predicted CHV
      US ORFs by Northern analysis.

PMID- 9620208
TI  - Mapping the antigenic structure of porcine parvovirus at the level of peptides.
AB  - The antigenic structure of the capsid proteins of porcine parvovirus (PPV) was
      investigated. A total of nine linear epitopes were identified by Pepscan using
      porcine or rabbit anti-PPV antisera. No sites were identified with a panel of
      neutralising monoclonal antibodies (MAbs). All epitopes were located in the
      region corresponding to the major capsid protein VP2. Based on this information,
      and on analogy to other autonomous parvoviruses, 24 different peptides were
      synthesised, coupled to keyhole limpet haemocyanin (KLH) and used to immunise
      rabbits. Most antisera were able to bind viral protein. Only peptides from the N
      terminal part of VP2 were able to induce virus-neutralising antibodies, although
      at low levels. A similar neutralising activity could be obtained in pigs. The
      exposure of the N-terminus was shown in full virions, both by immunoelectron
      microscopy and absorption experiments. It is concluded that in PPV, the VP2 N
      terminus is involved in virus neutralisation (VN) and peptides from this region
      are therefore primary targets for developing peptide-based vaccines against this
      virus.

PMID- 9620209
TI  - Role of carbohydrate processing and calnexin binding in the folding and activity
      of the HN protein of Newcastle disease virus.
AB  - The role of carbohydrate processing and calnexin binding in the folding pathway
      and activity of the hemagglutinin-neuraminidase (HN) protein of Newcastle disease
      virus (NDV) was explored in infected cells using the inhibitor castanospermine
      (CST). Calnexin-HN protein complexes were demonstrated by coimmunoprecipitation
      using antibody specific for calnexin or HN protein. As in other systems, this
      complex was not detected in CST treated cells. In cells incubated in CST, the
      synthesis and stability of the HN protein was unaffected. However, as monitored
      by the appearance of conformationally sensitive antigenic sites, the folding of
      the HN protein in CST treated cells was approximately twice as slow than in
      untreated cells. This folding was ultimately efficient since there was no
      evidence for significant amounts of irreversibly aggregated forms which never
      acquired a mature conformation. Most significantly, the folding sequence as
      measured by the order of appearance of conformationally sensitive antigenic sites
      (McGinnes and Morrison, Virology 199, 255) was unaffected by CST. Thus while
      calnexin functions to speed the folding of the HN protein, it is not required for
      the folding of this protein. In addition, the protein synthesized in the presence
      of CST had significant levels of neuraminidase and hemagglutination activity
      suggesting that processing of the carbohydrate has a minimal role in the activity
      of the protein.

PMID- 9620210
TI  - The nucleotide sequence and genome organization of the whitefly transmitted
      sweetpotato mild mottle virus: a close relationship with members of the family
      Potyviridae.
AB  - Primers corresponding to conserved regions in the RNA-dependent RNA polymerase
      and the RACE procedure led to the cloning of the complete sweetpotato mild mottle
      virus (SPMMV) RNA genome. The assembled SPMMV genomic sequence was 10,818
      nucleotides in length with a polyadenylated tract at the 3' terminus. The
      structure and organization of the SPMMV genome appear to be similar to those of
      potyviruses and rymoviruses. A 5' untranslated region, rich in A and U residues,
      is present between nucleotides 1 and 139. A putative initiation codon, at
      nucleotides 140-142, marks the beginning of a large open reading frame (ORF)
      which ends in UAA at positions 10,508-10,510. A 308-nucleotide untranslated
      region is present between the termination codon of the ORF and the beginning of
      the 3' polyadenylated region. Almost all known potyvirus motifs are present in
      the polyprotein of SPMMV. However, motifs in the putative helper-component and
      coat protein of SPMMV are incomplete or missing, which may account for its vector
      relations. Despite similarities with rymoviruses, potyviruses and, to a lesser
      extent, bymoviruses, comparative sequence analyses demonstrated that SPMMV
      belongs to a distinct genus of the family Potyviridae.

PMID- 9620211
TI  - The varicella zoster virus glycoprotein B (gB) plays a role in virus binding to
      cell surface heparan sulfate proteoglycans.
AB  - Varicella-zoster virus (VZV) interacts with cell surface heparan sulfate
      proteoglycans during virus attachment. In the present study, we investigated the
      potential involvement of two VZV glycoproteins, gB and gE, in the virus
      adsorption process. We showed that gB, but not gE, binds specifically to cellular
      heparan sulfate proteoglycans (HSPGs). Indeed, soluble recombinant gB protein
      (recgB) was found to bind to immobilized heparin and to MRC5 and L cells, a
      binding which was inhibited by heparin. Furthermore, recgB binding to two heparan
      sulfate-minus mutant L cell lines, gro2C and sog9 cells, was markedly reduced as
      compared to the parental L strain. Under the same experimental conditions,
      soluble recombinant VZV gE protein did not interact with heparin or with cell
      surfaces. We also demonstrated that the gB-HSPGs interactions were relevant to
      the VZV attachment to cells. Indeed, although polyclonal antibodies directed to
      gB did not impair the VZV binding, recgB could delay the virus adsorption. Our
      results thus strongly suggest that the interactions between gB and heparan
      sulfate proteoglycans take part in the initial VZV attachment to cell surfaces.

PMID- 9620212
TI  - Detection of negative-stranded hepatitis C virus RNA using a novel strand
      specific reverse transcription-polymerase chain reaction.
AB  - We developed a novel single-tube reverse transcription-polymerase chain reaction
      (RT-PCR) for the specific detection of negative-stranded hepatitis C virus (HCV)
      RNA. By using in vitro synthesized positive- and negative-stranded HCV RNAs, it
      was demonstrated that as few as 50 copies of negative-stranded HCV RNA could be
      specifically detected with a set of primers that amplify a 232-base pair sequence
      unique to the 5'-non-coding region of HCV RNA, while 10(8) copies of positive
      stranded HCV RNA were not detected. In addition, we demonstrated that this method
      allows the detection as few as 100 copies of negative-stranded HCV RNA even with
      the coexistence of a 100-fold excess of positive-stranded HCV RNA. Furthermore,
      with this method, negative-stranded HCV RNA was detected in RNAs from liver
      biopsy specimens obtained from patients with chronic hepatitis C, but not in RNAs
      from HCV-positive sera.

PMID- 9620213
TI  - Typing of European strains of parvovirus B19 by restriction endonuclease analyses
      and sequencing: identification of evolutionary lineages and evidence of
      recombination of markers from different lineages.
AB  - European isolates of parvovirus B19 were analyzed by restriction enzyme analysis
      of PCR products of the VP1/2 coding region and sequencing of the same amplified
      region, five cloned fragments from each PCR product. Two main groupings were
      found based on three perfectly linked point deviations. On the assumption that
      identical point deviations causing the various restriction patterns regardless of
      time and origin of virus isolation were unlikely to emerge independently in
      different evolutionary lineages, traits of evolutionary lineages were identified,
      suggesting a clonal population structure of global circulating B19 strains.
      However, combinations of markers from different evolutionary lineages were also
      found, particularly in a strain derived from an individual chronically infected
      with B19 for more than 7 years. As chronically infected individuals might be
      subject to superinfections due to contacts or possibly due to blood transfusions
      or the administration of gamma-globulin, it is suggested that coexistence of, and
      recombination between variants of B19 of different phylogenetic origin
      incidentally occur in such individuals.

PMID- 9620214
TI  - Challenges associated with evaluating the clinical utility of non-cytotoxic
      pharmaceutical agents in oncology.

PMID- 9620215
TI  - A retrospective and prospective overview of prostate-specific antigen.
AB  - Since the identification of prostate-specific antigen (PSA), continued
      technological advances have provided highly sensitive assays for its
      quantification. Given its lack of disease specificity, and its recent detection
      at low levels in an increasing number of non-prostatic tissues, PSA is far from
      being the perfect "tumour" marker (biological marker). However, the positive
      predictive value of PSA for assessing cancer risk makes PSA the most useful
      "tumour" marker for monitoring progression and response to treatment among
      patients with prostate cancer. Earlier detection through screening for elevated
      levels of PSA, while controversial, has been proposed as a way to decrease
      prostate cancer mortality. Haematogenous identification of PSA mRNA may provide
      stage-related prognostic information, and the use of ultrasensitive assays for
      PSA may permit earlier identification of residual or recurrent cancer, following
      treatment and the initiation of adjuvant therapy. Various PSA-related concepts,
      including the ratio of "free" PSA and complexes of PSA with the protease
      inhibitor, alpha1-antichymotrypsin, to total PSA, have been proposed and placed
      within diagnostic and management algorithms. Elevations of PSA in other
      irregularities of the prostate, notably in benign prostatic hyperplasia, and the
      increasing frequency and number of non-prostatic tissues, including those in
      women, expressing PSA, have implications for future immunoassays for PSA and
      strategies for immunotherapy using PSA-based monoclonal antibodies or vaccines,
      as well as for the molecular basis for its anomalous expression and physiological
      function(s).

PMID- 9620216
TI  - 5-fluorouracil/leucovorin-induced inhibition of thymidylate synthase in normal
      tissues of mouse and man.
AB  - We evaluated the effects of 5-fluorouracil (5FU) and leucovorin (LV) on
      thymidylate synthase (TS) in normal rapidly dividing tissues, which may
      contribute to toxic side-effects of treatment with 5FU and LV. TS levels were
      determined in biopsies of human liver and colon mucosa and murine bone marrow,
      liver and intestinal mucosa at several time points after administration of
      therapeutic doses of 5FU or LV/5FU. In murine liver, after treatment with 100
      mg/kg 5FU, TS inhibition was significantly higher than after LV/5FU
      administration (P < 0.001). A similar trend was observed in human liver tissue.
      Murine intestinal mucosa had TS levels below the limit of detection after 5FU or
      LV/5FU treatment. In human colon mucosa samples, administration of 500 mg/m2 5FU
      resulted in a large extent of TS inhibition but the small number of samples did
      not allow a time- or 5FU-LV/5FU-related evaluation. TS activity in murine bone
      marrow cells was strongly inhibited to 10% of the control value during 48 h.
      LV/5FU administration resulted in a slightly higher inhibition. No human bone
      marrow was available to measure TS levels. Both in mice and humans the most
      pronounced TS inhibition occurred in the tissue that was involved in dose
      limiting toxicity. Therefore it is very likely that TS inhibition in normal
      tissues contributes to the toxic side-effects of 5FU treatment.

PMID- 9620217
TI  - Involvement of MHC class I molecule and ICAM-1 in the enhancement of adhesion and
      cytotoxic susceptibility to immune effector cells of tumor cells transfected with
      the interleukin (IL)-2, IL-4 or IL-6 gene.
AB  - To investigate the molecular and cellular mechanisms involved in the reduced
      tumorigenicity and increased immunogenicity of interleukin-2 (IL-2)-, IL-4- or IL
      6-gene-transfected B16 melanoma vaccine, we have analyzed the functional and
      phenotypic properties of these genetically engineered melanoma cells in the
      present study. The cytokine-gene-transfected B16 melanoma cells showed stronger
      adhesion to the lymphokine-activated killer (LAK) cells or cytotoxic T
      lymphocytes (CTL), and higher sensitivity to cytotoxicity of LAK cells or CTL.
      Using fluorescence-activated cell sorting analysis, we found that both MHC class
      I and ICAM-1 expression were increased after IL-2, IL-4 or IL-6 gene
      transfection. The increased level of MHC class I and ICAM-1 expression seems to
      be responsible for the high sensitivity of these gene-transfected B16 cells to
      LAK or CTL cytotoxicity because anti-(MHC class I) or anti-ICAM-1 mAb could
      inhibit the adhesion and cytotoxicity increment simultaneously. The CTL induction
      was partly inhibited by anti-ICAM-1 mAb and was completely blocked by anti-MHC
      class I mAb. These results suggested that the decreased tumorigenicity of IL-2-,
      IL- 4-, and IL-6-gene-transfected B16 melanoma cells may be partly due to the
      increased sensitivity to effector cell cytotoxicity mediated by increased
      expression of ICAM-1 or MHC class I molecules on the tumor cell surface after
      cytokine gene transfection.

PMID- 9620218
TI  - Expression and purification of single-chain anti-HBx antibody in Escherichia
      coli.
AB  - Monoclonal antibodies have been widely used in tumor targeting studies with
      promising results. However, their clinical application has been limited by
      heterogeneity and macro-molecular movement of murine antibody. In this study, the
      variable-region (heavy- and light-chain) fragments of anti-HBx monoclonal
      antibody were enriched by the polymerase chain reaction. The expression vector,
      which included a 6x histidine sequence in the 3' terminus of the HBx single-chain
      antibody (sFv) was recombined with a linker sequence (KLGGGGFSGA) between the
      variable regions. The expression product from Escherichia coli fused with 6xHis
      was purified by nickel (Ni2+) nitrilotriacetate chelating resin. The results of
      enzyme-linked immunosorbent assay and Western blotting showed that sFv had
      binding affinity with HBxAg, suggesting that it could become a novel targeting
      carrier in clinical trials.

PMID- 9620219
TI  - Intratumoral depot interleukin-2 therapy inhibits tumor growth in Dunning
      adenocarcinoma of the prostate implanted subcutaneously in rats.
AB  - The purpose of this study was to determine the effectiveness and toxicity of
      local continuous immunotherapy of prostatic cancer. A group of 60 young male
      Copenhagen rats with Dunning adenocarcinoma of the prostate, implanted
      subcutaneously into both flanks, after proven tumor growth, were treated with
      either human interleukin-2 (IL-2) depot preparations (n = 30) or albumin
      (placebo) depot preparations (n = 30) implanted directly into one tumor site. IL
      2 depots released IL-2 reliably for more than 24 days. The rat serum was tested
      during treatment for human IL-2, possibly absorbed from depots, and for rat
      interferon gamma. IL-2 treatment reduced tumor growth significantly (P < 0.001)
      compared with albumin-treated sites or untreated contralateral sites. No toxicity
      was observed during treatment. Neither human IL-2 nor rat interferon gamma was
      detected in the serum, which indicates an exclusively local IL-2 effect. IL-2
      depot preparations reduce tumor growth in Dunning adenocarcinoma of the prostate
      significantly without toxicity.

PMID- 9620220
TI  - Effect of glutathione-modulating compounds on hydrogen-peroxide-induced
      cytotoxicity in human glioblastoma and glioma cell lines.
AB  - The relation between the intracellular glutathione (GSH) concentration and
      hydrogen-peroxide(H2O2)-induced cytotoxicity was investigated. The intracellular
      GSH concentration in human glioblastoma (T98G, U87MG) and glioma (KG1C) cell
      lines was one or two orders of magnitude higher than that in a human myelogenous
      leukemic cell line (HL-60), which showed higher sensitivity to H2O2. Pretreatment
      of these cell lines with L-buthionine-[S,R]-sulfoximine, which significantly
      reduced the intracellular GSH concentration, increased their sensitivity against
      H2O2, whereas pretreatment with N-acetyl-L-cysteine, which did not significantly
      change the intracellular GSH concentration, only marginally protected the cells
      from the cytotoxic effect of H2O2. The results suggest that drug sensitivity of
      tumor cells can be modified by glutathione-modulating compounds.

PMID- 9620221
TI  - Thiazolidinyl- and perhydrothiazinylphosphamidesters: toxicity and preliminary
      antitumour evaluation.
AB  - Aldophosphamide thiazolidine (NSC 613060) and aldophosphamide perhydrothiazine
      (NSC 612567), which hydrolyse spontaneously to 4-hydroxycyclophosphamide (4-OH
      CP) in aqueous solution, were synthesised. These substances are prototypes of a
      new class of prodrugs for activated oxazaphosphorines. They were developed
      according to our hypothesis on the mechanism of action of oxazaphosphorine
      cytostatics. According to this hypothesis, toxicity and canceroselectivity are
      the results of phosphoramide mustard (PAM) release from 4-OH-CP catalysed by two
      classes of phosphodiesterase. 4-OH-CP toxicity results (a) from oxazaphosphorine
      specific toxicity due to reactivity of the hemiaminal group with thiol groups of
      membrane proteins and (b) from PAM release catalysed by ubiquitous
      phosphodiesterases present in blood and tissues. Specific cytotoxicity suitable
      for antitumour therapy is based on specific PAM release in the vicinity of the
      target molecule DNA by the exonuclease subsites of DNA polymerases delta and
      epsilon. To unfold this specific core, which, we assume, improves efficacy in
      cancer treatment, low, long-lasting concentrations of OH-CP have to be guaranteed
      beneath the affinity range of the ubiquitous phosphodiesterase. This goal is
      facilitated by the rapid transfer of 4-OH-CP released from the perhyrothiazine
      derivative NSC 612567 to protein SH groups, as shown by protein-binding studies.
      Half-lives of hydrolysis and dissociation constants of the thiazolidine and
      perhydrothiazine derivatives, in which the reactivity of the hemiaminal group is
      inactivated by inclusion into the thiazolidine or perhydrothiazine ring, were
      determined to be 23 h and 6.0 x 10(-6) mol/l for NSC 613060 and 1.5 h and 1.1 x
      10(-4) mol/l for NSC 312567. Accordingly the compounds guarantee low but long
      lasting steady-state concentrations of 4-OH-CP. The acute toxicity determined in
      mice was 2400 mg/kg for NSC 613060 and 1900 mg/kg for NSC 612567. Except for a
      30% decrease in leucocytes, daily i.p. injections of 260 mg/kg NSC 612567 (15% of
      LD50) were tolerated without signs of toxicity over a period of 4 weeks. In
      contrast, equitoxic doses of cyclophosphamide caused severe signs of toxicity,
      only five daily applications were tolerated. In mice treated repeatedly with NSC
      613060, oxazaphosphorine toxicity was overlapped by thiazolidine toxicity.
      Scheduled activity tests in mice bearing P815 ascites tumour showed optimal
      therapeutic response when mice were treated daily. Repeated applications of 4%
      LD50 of NSC 613060 and 13% LD50 of NSC 612567 prevented tumour growth in mice
      with advanced, P388 lymphomas, implanted subcutaneously, without signs of overall
      toxicity to the host.

PMID- 9620222
TI  - Soluble intercellular adhesion molecule-1 in patients with lung cancer and benign
      lung diseases.
AB  - Intercellular adhesion molecule-1 (ICAM-1) expression correlates with tumour
      progression in patients with malignant melanoma or renal cell carcinoma. To
      assess the value of soluble ICAM-1 (sICAM-1) for lung cancer patients, sICAM-1
      was determined by means of an enzyme-linked immunosorbent assay. Sera from 147
      patients with lung cancer, from 75 patients with benign lung diseases and from
      108 healthy adults were investigated for sICAM-1 expression. Significant
      differences in sICAM-1 levels were detected in lung cancer patients (387 +/- 176
      ng/ml) and patients with benign lung diseases (365 +/- 110 ng/ml) compared to the
      group of healthy adults (310 +/- 90 ng/ml). There was no difference in sICAM-1
      level among the subtypes of lung cancer. Advanced tumour stages and patients with
      progressive disease tended to be associated with higher sICAM-1 levels, the site
      of metastasis being relevant for the level attained. Patients with liver
      metastasis had the highest sICAM-1 levels (547 +/- 295 ng/ml) compared to
      patients with cerebral metastasis (317.8 +/- 92.2 ng/ml). An increase of sICAM-1
      expression during the progression of the disease coincided with a poorer survival
      prognosis for the patients compared to patients with stable or falling sICAM-1
      levels.

PMID- 9620223
TI  - Iodized oil enhances the thermal effect of high-intensity focused ultrasound on
      ablating experimental liver cancer.
AB  - The influence of the biological medium on high-intensity focused ultrasound
      (HIFU) therapy for ablating experimental liver cancer was studied. In study 1,
      the temperature rise in the focal zone in the presence of iodized oil or castor
      oil was observed in vitro. The results showed that HIFU with iodized oil produced
      a higher and faster temperature rise than did HIFU with castor oil, whether high
      power (500 W/cm2) or relatively low-power (136 W/cm2) conditions were used (P =
      0.0008 and P = 0.0004 respectively). With the excised liver samples, the
      temperature also rose higher and more rapidly after injection of iodized oil into
      the liver than when castor oil was injected (P = 0.0239), and the target liver
      tissue revealed more radically and extensive destruction with iodized oil than
      with castor oil. In study 2, 48 nude mice, bearing primary liver cancer LTNM4
      implanted subcutaneously, were randomly divided into four groups. Group I (n =
      12) were the controls, group II (n = 12) were injected with iodized oil alone,
      group III (n = 12) received HIFU treatment, and group IV (n = 12) were exposed to
      HIFU after iodized oil injection. Significant inhibition of tumor growth was seen
      in groups III and IV as compared with group I or group II (P < 0.05), the tumor
      growth inhibition rate on the 28th day after treatment being 87% and 93%
      respectively. Significantly improved survival was noted in groups III and IV
      compared with groups I and II (P < 0.05). Histologically, group IV showed more
      complete tumor necrosis than did group III. These data suggest that HIFU combined
      with iodized oil might have achieve of synergism, location and targeting in the
      treatment of liver cancer.

PMID- 9620224
TI  - Primary study of neovasculature correlating with metastatic nasopharyngeal
      carcinoma using computer image analysis.
AB  - The significance of neoangiogenesis in the metastasis of nasopharyngeal carcinoma
      (NPC) was investigated to clarify the role neovascularity in the prognosis of NPC
      and the probability of antiangiogenesis preventing NPC from distant metastasis. A
      group of 52 patients presenting with metastatic NPC were selected and strictly
      paired one-to-one, in sex, age, T stage, and N stage, with another 52 patients
      with non-metastatic NPC, who had survived for a long time after therapy. The
      tumor tissues of all 104 patients were retrieved for computer-assisted,
      immunohistochemical analysis of tumor vasculature. Counts of the microvessels and
      the relative area of all microvessels per image were significantly higher in
      metastatic NPC than they were in curable, non-metastatic NPC, while the average
      area of the microvessels and their average perimeter of in metastatic NPC were
      smaller than in non-metastatic disease. No significant difference in any
      microvessel parameter was found among the various types of metastasis. The
      alterations of microvessel parameters were significantly linked to the metastasis
      of NPC. Evaluation of neovascularity by computer image analysis may be helpful in
      estimating the prognosis of NPC and in determining the indicators for aggressive
      multimodal treatments.

PMID- 9620225
TI  - Expression of type IV collagenase correlates with the expression of vascular
      endothelial growth factor in primary non-small cell lung cancer.
AB  - Tumor growth and metastasis are angiogenesis-dependent processes initiated and
      regulated by a number of cytokines. Vascular endothelial growth factor (VEGF) is
      a potent angiogenic protein with a selective mitogenic effect on vascular
      endothelial cells, known to be involved in physiological (embryogenesis) and
      pathophysiological (rheumatoid arthritis, tumor) angiogenesis. An increased
      expression of matrix metalloproteinase type IV collagenase has been reported in
      invading endothelial cells in vitro and in malignant cells, degrading structures
      of the basement membranes in various human malignancies. In the present study we
      investigated the expression of the genes for type IV collagenase and vascular
      endothelial growth factor (VEGF) in 40 cases of primary non-small-cell lung
      cancer (NSCLC). Specimens were immunostained by an antibody directed against VEGF
      and mRNA transcripts of VEGF and type IV collagenase were localized by non
      radioactive in situ hybridization. VEGF mRNA was detected in 33 neoplasms, while
      in 23 cases transcripts of the type IV collagenase gene were visualized by
      digoxigenin-labeled cDNA probes. Transcripts of both mRNAs were detected in
      malignant cells. Furthermore, anti-VEGF immunostaining was present in newly
      formed microvessels close to the atypical cells, and mRNA of type IV collagenase
      was present in stromal cells adjacent to the tumor. A statistically significant
      correlation was found between the expression of type IV collagenase and VEGF (P =
      0.0061). These data suggest a double role for type IV collagenase in the
      metastatic process of NSCLC: (1) facilitating the invasion of tumor cells by the
      proteolytic cleavage of the basement membrane and (2) similarly supporting the
      endothelial cell invasion essential for tumor angiogenesis. Furthermore, our
      findings sustain the hypothesis that metastatic spread and angiogenesis are
      associated with a clonal expansion of highly angiogenic and invasive tumor cell
      clones.

PMID- 9620226
TI  - Evidence for reduced copying fidelity of DNA polymerases alpha, delta, and
      epsilon from Novikoff hepatoma cells.
AB  - To investigate whether or not DNA polymerases alpha, delta, and epsilon from
      tumor cells have acquired properties that might be responsible for mutations
      found in tumor development, we investigated copying fidelities of DNA polymerases
      alpha, delta, and epsilon from the highly malignant Novikoff hepatoma cells and
      compared them to the corresponding enzymes from normal rat liver. DNA polymerases
      were purified more than 300-fold by three chromatographic steps. Copying fidelity
      was studied using steady-state kinetics and an 18-mer oligonucleotide primed with
      a 12-mer (13-mer for extension experiments) as DNA primer-template. Three
      experimental approaches were chosen: i) extension of DNA primers with mismatched
      3'-OH ends opposite dGMP, ii) DNA insertion of nucleotides opposite m6G in the
      template and iii) extension of DNA primers with mismatched 3'-OH ends opposite
      m6G. i) Extension of DNA primers with mismatched 3'-OH ends opposite dGMP. DNA
      primer templates containing G:T and G:A mispairs at the 3'-OH position of the
      primer were easily extended by DNA polymerases alpha, delta and epsilon from both
      normal rat liver and Novikoff hepatoma cells. The G:G mismatch was elongated with
      low efficiency. Notably, DNA polymerase alpha from Novikoff hepatoma cells
      extended G:A and G:G mismatches significantly faster than the enzyme from normal
      cells. ii) Insertion of nucleotides opposite m6G. DNA polymerases alpha, delta,
      and epsilon from normal rat liver preferably catalyzed incorporation of dAMP
      opposite m6G at dNTP concentrations < 100 microM. When dNTP concentrations were
      raised to > or = 100 microM, dCMP (DNA polymerases delta and epsilon) and dTMP
      (DNA polymerase alpha) were also incorporated. The same insertion characteristics
      were found for the enzymes from Novikoff cells, however, insertion efficiencies
      of dAMP and dCMP were significantly higher for polymerases delta and epsilon.
      iii) Extension of primers with mismatched 3'-OH ends opposite m6G. Only m6G:dAMP
      and m6G:dCMP mismatches were extended by DNA polymerases alpha, delta and epsilon
      from both sources. No differences in extension efficiency were observed between
      the enzymes from normal and hepatoma cells. Taken together, our results suggest
      that DNA polymerases alpha, delta, and epsilon from Novikoff cells catalyzed
      incorporation of the wrong nucleotides more readily and extended mismatches more
      easily. These results may provide a rationale why numerous mutations accumulate
      during tumor development.

PMID- 9620227
TI  - Establishment of new epithelial carcinoma cell lines by blocking monolayer
      formation.
AB  - Human endometrial carcinoma cell lines were established by using a new cell
      culture technique. The malignant endometrial tumors were grossly disaggregated by
      mechanical means and cultivated in suspension culture. Adhesion to the bottom of
      the culture flasks was prevented by first coating the flasks with a thin agarose
      layer. Four cell lines were derived from 17 samples by this new technique. The
      cell lines obtained in this way were fully characterized, including karyotyping,
      intermediate filament staining and transplantation to nude mice. This new
      technique of initial suspension culture may also be applicable to other human
      tumors that are equally difficult to cultivate in vitro.

PMID- 9620228
TI  - Bone and soft tissue sarcomas: summary of the Third United States/Japan Clinical
      Trials Summit (Seattle, Washington).

PMID- 9620229
TI  - Acute myelomonocytic leukemia secondary to synchronous carcinomas of the breast
      and lung, and to metachronous renal cell carcinoma.
AB  - We describe a patient in whom synchronous breast cancer and small-cell lung
      cancer, and metachronous renal cell carcinoma were diagnosed within an 11 months
      period. All three tumors were treated surgically, followed by administration of
      tamoxifen, adjuvant chemotherapy with etoposide (2.8 g/m2 total) and vindesine,
      and administration of interferon alpha and flutamide. The patient developed acute
      myelomonocytic leukemia 26 months after discontinuation of etoposide-containing
      chemotherapy. This pattern of multiple neoplasms fits the wider disease spectrum
      associated with germline mutations of the p53 gene; however, analysis of p53
      exons 5-8 did not disclose any sequence abnormalities in this patient. In
      conclusion, clustering of four (synchronous and metachronous) malignancies may on
      rare occasions occur in an individual patient and in the absence of a family
      history of cancer; the sequence during which treatment of primary malignancies
      may result in treatment-related acute myelocytic leukemia is discussed.

PMID- 9620231
TI  - Introducing quality assurance in radiotherapy.
AB  - Introducing a Quality Assurance methodology appears particularly useful in
      Radiation Oncology due to the complexity of the procedures involved and the
      heterogeneity of the standards adopted, if any, in the great majority of the
      Centers. There are two possible ways of evaluating quality in the Health
      Environment: a formal, Institutional certification, or a voluntary one obtained
      through a mechanism of peer review. The European Society for Therapeutic
      Radiology and Oncology (ESTRO) started in 1994 with the publication of a
      methodological Report intended to be adopted by the individual national
      Societies, and this paper is an invitation to do it.

PMID- 9620230
TI  - Continuing medical education in radiation oncology.
AB  - Continuing medical education (CME) has always been considered very important in
      modern medical practice. Physicians should not be left completely free to
      continuously educate themselves, but they should receive at least a minimal level
      of education accredited by scientific and/or Government Institutions. The main
      goal of CME is to improve the quality of medical practice. In order to adequately
      define programs and contents of CME in radiation oncology, we must first identify
      the professional profile of the radiation oncologist: he is a physician engaged
      in the clinical practice of oncology, and in particular in the loco-regional cure
      of cancer by sophisticated technologies; he has the responsibility of diagnosis,
      treatment, follow-up and supportive care of cancer patients, collaborating within
      a multidisciplinary approach with the radiologist, the medical oncologist, the
      surgeon and the medical physicist. The european core curriculum in radiotherapy
      and the procedures employed in the daily practice could be models to develop
      postgraduate teaching and CME for the radiation oncologists in Italy. In fact,
      many countries, such as the USA, France, Belgium and the United Kingdom, have
      already developed accredited programs of CME. Unfortunately, Italy still lacks
      this type of program. What is mostly needed to implement CME activities is a
      close cooperation between representatives of radiation oncology associations and
      Government Institutions to define laws, programs, an Accreditation Council, a
      minimum of formative credits, accredited categories of education regulating CME,
      as well as the resources devoted to it.

PMID- 9620233
TI  - Supportive care in radiotherapy: a review.
AB  - The normal tissue tolerance and the related early side effects represent the main
      constraint on the total radiation dose which can be administered to the target
      volume. The most common disorders during radiotherapy or chemo-radiotherapy are
      summarized in this review. Since in the recent years great advances have been
      made towards the improvement of acute tolerance, practically every adverse
      symptoms can be controlled or lowered with an adequate treatment. Some
      suggestions are reported in order to prevent or lower the degree and the
      incidence of major complications, specifically mucositis-related symptoms like
      stomatitis, diarrhea, cystitis. Possibly, a multicenter effort is to be made in
      order to optimize the quality of supportive care for irradiated patients in all
      radiation therapy centers.

PMID- 9620232
TI  - Immobilization devices between routine and quality assurance.
AB  - AIMS AND BACKGROUND: To evaluate the impact of immobilization devices in reducing
      treatment errors and delivering high doses to limited target volumes. The clear
      advantages are matched with quality control necessity. METHODS: The Authors
      examine two fundamental aspects of the topic: 1) the immobilization of head and
      neck and the relative implications in reducing the skin-sparing at the build-up
      region; 2) the rationale and management of quality assurance procedures in the
      immobilization devices utilization, with a particular reference to pelvic
      radiation treatment. CONCLUSIONS: The immobilization devices utilization
      certainly leads to an optimization in the execution of radiation treatments.
      Nevertheless, in the choice for their routine use, the Authors suggest to follow
      some "conceptual rules" with the aim of successfully matching each of the
      discussed aspects connected with their utilization.

PMID- 9620234
TI  - Advances in treatment with intensity-modulated conformal radiotherapy.
AB  - The modern practice of radiotherapy centres on the development of conformal
      radiotherapy, techniques to ensure the high-dose volume is tightly wrapped around
      the diseased tissue and excluded as far as possible from adjacent normal
      structures. The development of conformal radiotherapy is a chain of processes
      involving treatment planning, development of new methods to deliver radiation,
      verification of the accuracy of radiation delivery and improvement of biological
      outcome. This is an enormous field of activity. This invited review paper
      summarises some of the main elements of progress towards implementing intensity
      modulated conformal radiotherapy. This is the newest and most exciting
      development and, when achieved clinically, will lead to a quantum leap in tumour
      control probability with a fixed level of normal tissue damage.

PMID- 9620235
TI  - Innovations in three-dimensional treatment planning and quality assurance.
AB  - Radiation therapy treatment planning and treatment delivery are in the process of
      changing dramatically over the next several years. This change has been driven in
      large part by continued advances in computer hardware and software and in medical
      imaging. Three-dimensional radiation treatment planning systems are rapidly being
      implemented in clinics around the world. These developments in turn have prompted
      manufacturers to employ advanced microcircuitry and computer technology to
      produce treatment delivery systems capable of precise shaping of dose
      distributions via computer-controlled multileaf collimators which cause the beam
      intensity to be varied across the beam. Image-based 3D planning and beam
      intensity modulated delivery systems show significant potential for improving the
      quality of radiotherapy and improving the efficiency with which radiation therapy
      can be planned and delivered. However, significant research and development work
      on these systems and their clinical use remains to be performed. The techniques
      used for the treatment planning and the methods used for quality assurance
      procedures and testing must all be revised and/or redesigned to allow efficient
      clinical use of these technological advances. Although much of the current 3D
      radiation therapy process requires interactive tasks (and some still very
      laborious) the path is clear toward solving the technological obstacles so that a
      nearly automated planning, delivery, and verification system will become a
      reality over the next decade. Such systems will allow radiation oncologists to
      significantly increase dose to many tumor sites while concomitantly lowering
      doses to critical organs-at-risk. Most of the tasks will be automated, thus
      lowering the overall costs currently needed to provide high-quality external beam
      radiation therapy.

PMID- 9620236
TI  - Radiobiological models of tissue response to radiation in treatment planning
      systems.
AB  - AIMS: To present several biological concepts and models of tissue response to
      fractionated radiotherapy. To describe practical implementation of these models
      in three-dimensional treatment planning systems. METHODS: Models of cell
      survival, Equivalent Uniform Dose (EUD) and Tumor Control Probability (TCP) are
      discussed. These models are based on the target-cell hypothesis which assumes
      that response of organs and tissues to radiation therapy can be explained and
      mathematically described in terms of survival of the specific target-cells.
      RESULTS: Several formulae for deriving and calculating EUD and TCP for a given
      three-dimensional dose distribution are presented and discussed. CONCLUSIONS:
      Biological models of tissue response to radiation, when used wisely, have a
      potential to be useful in radiation therapy treatment planning. The models can
      advance our understanding of the underlying biological mechanisms, and may help
      in designing new and better treatment strategies. They should be particularly
      useful in modern conformal radiotherapy where treatment strategy for each patient
      can be individualized and optimized according to patient characteristics and
      available technology of delivering sophisticated treatment plans.

PMID- 9620237
TI  - Radiotherapy treatment verification.
AB  - During a radiotherapy treatment, a dosimetric verification or a geometric
      localization can be done, in order to assess the quality of the treatment. The
      dosimetric verification is generally performed measuring the dose at some points
      inside (natural cavities) or outside the patient, and comparing it to the dose at
      the same points calculated and predicted by the treatment planning system. This
      can be done either with thermoluminescent or diodes dosimeters or with ionization
      chambers. The geometric localization can be done acquiring a portal image of the
      patient. Portal imaging can be performed either with films placed between
      metallic screens, or with an electronic portal imaging device such as
      fluoroscopic systems, solid state devices or matrix ionization chamber systems.
      In order to assess possible field placement errors, the portal images have to be
      compared with images obtained with the simulator in the same geometric conditions
      and/or with the digitally reconstructed radiograph (DRR) obtained with the
      treatment planning system. In particular, when using matrix ionization chamber
      systems, the portal images contain also information regarding the exit dose. This
      means that this kind of imaging device can be used both for geometric
      localization and for dosimetric verification. In this case, the exit dose
      measured by the portal image can be compared with the exit dose calculated and
      predicted by the treatment planning system. Some "in-vivo" applications of this
      methodology are presented.

PMID- 9620238
TI  - Two quality control procedures on radiotherapy beam calibration and treatment
      planning system implementation.
AB  - New challenging dosimetric approaches, such as narrow beams and 3D algorithms,
      are being used in radiotherapy. In this paper two quality control (QC) procedures
      are reported. The first one concerns the QC of the dosimetry of small x-ray
      beams, generally carried out by using silicon detectors. The comparison of dose
      values obtained by a silicon diode, a diamond detector, and radiochromic films
      shows that for x-ray beams of high energy, the silicon diode can give an
      overestimation of the output factors in phantom, up to 4%. This is due to the
      higher than unit density silicon diode and the surrounding envelope that restore
      the lateral electron equilibrium. About the 3D algorithms for breast treatment
      planning, a quality control test has been adopted to verify the accuracy of the
      computed dosimetry when "loss of scatter" occurs. The results show a sensible
      agreement (within 1.5%) between computed and experimental data.

PMID- 9620239
TI  - Altered fractionation in radiotherapy.
AB  - Differences between late-responding (slowly proliferating) normal tissues and
      early-responding (rapidly proliferating) normal tissues and tumor cells and the
      event of tumor cell repopulation occurring during treatment have essentially led
      to the development of altered fractionation schemes. Altered fractionation
      regimens mainly refer to schedules utilising two or more (small dose) fractions
      per day for part of or for the entire treatment course. It must be underlined
      that a true standard or conventional fractionation regimen does not exist: no
      schedule is universally recognised as the standard of reference to be compared
      with. However, continental European and U.S. conventional regimens are the
      considered control arm with which the new experimental regimens have to be
      compared. For this reason they are generally recognised as the standards. The
      basic rationale for hyperfractionated or accelerated regimens respectively lies
      in the possibility (a) to deliver higher total doses reducing late-responding
      normal tissue damage, (b) to deliver total doses in a reduced overall treatment
      time to defeat tumor clonogen repopulation. Multiple fractions per day should not
      be delivered with interfraction intervals smaller than 6 hours. Clinical results
      of phase I-II and limited but convincing phase III randomised trials suggest that
      a therapeutic benefit can be achieved with new altered regimens.

PMID- 9620240
TI  - Randomized trials on altered fractionation in head and neck cancer radiotherapy
      with conventional fractionation as control arm: another lap to go.
AB  - The Authors present a review of randomized trials on non conventional
      fractionation in head and neck cancer radiotherapy with conventional
      fractionation as control arm. Hyperfractionation was studied in 5 trials,
      accelerated hyperfractionation in 4 trials and accelerated fractionation in 3
      trials. Furthermore, the reviews of eminent Authors dealing with the above
      mentioned trials are summarized. In spite of improved local control rate reported
      with hyperfractionation, non conventional radiotherapy schedules are not yet
      recommended as routine clinical practice, but all the radiation oncologists are
      Invited to join trials on this subject.

PMID- 9620241
TI  - Non conventional fractionation in radiotherapy of the musculo-skeletal sarcomas.
AB  - In 1989 we started an accelerated hyperfractionated schedule of radiotherapy (two
      1.6 Gy daily fractions) in standard risk localized Ewing's sarcoma of bone, with
      the aim at reducing late effects in young patients and at improving disease
      control through a better integration of treatment modalities. From 1991, the same
      schedule was used in preoperative radiotherapy of adult soft tissue sarcomas of
      the extremities: the main purpose was to reduce the time to surgery and to
      evaluate surgical complications in comparison with a previous experience of
      hypofractionated radiotherapy (one 3 Gy daily fraction). From 1991 to 1997, 76
      patients with Ewing's sarcoma and 24 patients with soft tissue sarcoma were
      treated at our Institution. Results and complication rates are analyzed in
      comparison with historical data. In Ewing's sarcoma, a correct evaluation of
      improvement in local control was difficult because of changing treatment policy
      (bulky disease was not included in the present series). Late effects, as
      evaluated in patients with a minimum follow-up of 3 years, occurred with similar
      incidence, but at higher total dose levels in patients treated with accelerated
      hyperfractionation. In patients with soft tissue sarcomas, incidence of surgical
      complications is reduced as compared to historical experience. Major problems of
      wound healing were seen in association with intraoperative brachitherapy boost.

PMID- 9620242
TI  - Altered fractionation radiotherapy in lung cancer.
AB  - Clinical trials on altered fractionation radiotherapy (RT) regimens currently
      play a significant role in lung cancer, due to the importance of local control
      and to the disappointing therapeutic results in this disease. In non-small-cell
      lung cancer (NSCLC) two strategies are being actively investigated:
      hyperfractionation with a "curative" aim, and hypofractionation with a palliative
      aim; in small-cell lung cancer (SCLC) altered fractionation seems to play a minor
      role at this moment. In this review paper the results of reported randomised
      trials are summarised and discussed. Conclusions may indicate that through
      hyperfractionation, particularly if accelerated, clinical outcome of non
      metastatic NSCLC patients can be improved; data are however not sufficiently
      mature to advise its use outside controlled clinical trials. In the palliative
      setting, hypofractionation should be considered standard treatment.

PMID- 9620243
TI  - Clinical results of unconventional fractionation radiotherapy in central nervous
      system tumors.
AB  - Malignant brain tumors (primary and metastatic) are apparently resistant to most
      therapeutic efforts. Several randomized trials have provided evidence supporting
      the efficacy of radiation therapy. Attempts at improving the results of external
      beam radiotherapy include altered fractionation, radiation sensitizers and
      concomitant chemotherapy. In low-grade gliomas, all clinical studies with
      radiotherapy have employed conventional dose fractionation regimens. In high
      grade gliomas, hypofractionation schedules represent effective palliative
      regimens in poor prognosis subsets of patients; short-term survival in these
      patients has not allowed to evaluate late toxicity. In tumors arising within the
      central nervous system, hyperfractionated irradiation exploits the differences in
      repair capacity between tumour and late responding normal tissues. It may allow
      for higher total dose and may result in increased tumor cell kill. Accelerated
      radiotherapy may reduce the repopulation of tumor cells between fractions. It may
      potentially improve tumor control for a given dose level, provided that there is
      no increase in late normal tissue injury. In supratentorial malignant gliomas,
      superiority of accelerated hyperfractionated over conventionally fractionated
      schedules was observed in a randomized trial; however, the gain in survival was
      less than 6 months. At present no other randomized trial supports the
      preferential choice for altered fractionation irradiation. Also in pediatric
      brainstem tumors there are no data to confirm the routine use of
      hyperfractionated irradiation, and significant late sequelae have been reported
      in the few long-term survivors. Shorter treatment courses with accelerated
      hyperfractionated radiotherapy may represent a useful alternative to conventional
      irradiation for the palliation of brain metastases. Different considerations have
      been proposed to explain this gap between theory and clinical data. Patients
      included in dose/effect studies are not stratified by prognostic factors and
      other treatment-related parameters. This observation precludes any definite
      conclusion about the relative role of conventional and of altered fractionation.
      New approaches are currently in progress. More prolonged radiation treatments, up
      to higher total doses, could delay time to tumor progression and improve survival
      in good prognosis subsets of patients; altered fractionation may be an effective
      therapeutic tool to achieve this goal.

PMID- 9620244
TI  - Hadrontherapy in the world and the programmes of the TERA Foundation.
AB  - Hadrontherapy was born in 1938, when neutron beams were used in cancer therapy,
      but it has become an accepted therapeutical modality only in the last five years.
      Fast neutrons are still in use, even if their limitations are now apparent.
      Charged hadron beams are more favorable, since the largest specific energy
      deposition occurs at the end of their range in matter. The most used hadrons are
      at present protons and carbon ions. Both allow a dose deposition which conforms
      to the tumour target. Radiobiological experiments and the results of the first
      clinical trials indicate that carbon ions have, on top of this macroscopic
      property, a different way of interacting with cells at the microscopic level.
      There are thus solid hopes to use carbon beams of about 4500 MeV to control
      tumours which are radioresistant both to X-rays and protons. After discussing
      these macroscopic and microscopic properties of hadrontherapy, the hospital-based
      facilities, running or under construction, are reviewed. The conclusion is that,
      while in USA and Japan twelve of these centres will be running around the year
      2001, in Europe very little is foreseen to use hadrontherapy to treat deep-seated
      tumours. The most advanced programme is the Italian one, which is described in
      the last Sections of the report. The main activities concern the construction,
      near Milano, of a centre for protons and carbon ions called CNAO (National Centre
      for Oncological Hadrontherapy) and the development of new type of proton
      accelerators. The Istituto Superiore di Sanita in Rome obtained the initial
      financing for constructing, in collaboration with ENEA, a 3 GHz linac, which
      eventually will accelerate protons to 200 MeV, so as to allow deep protontherapy.
      These, and other hadrontherapy centres in Italy and Europe, will be connected
      with oncology centres, hospitals and clinics by a multimedial network called
      RITA, so that before referral each patient's case can be discussed directly by
      doctors, even located far away, with the experts sitting in the hadrontherapy
      centres.

PMID- 9620245
TI  - Radiotherapy with heavy ions: radiobiology, clinical indications and experience
      at GSI, Darmstadt.
AB  - In the history of external beam radiotherapy, the trend for a better conformation
      as well as for a higher biological efficiency has been the driving force for the
      improvement of clinical results. However, these two goals had to be followed with
      separate types of radiation, i.e. photons and neutrons, and could not be
      combined. For the first time being, beams of heavy ions like carbon offer the
      possibility to combine both advantageous properties: better targeting and higher
      biological efficiency. Particle beams have an inverse depth dose profile, with a
      maximum dose in the deep seated tumor, a finite range, small lateral scattering,
      and a drastically increased biological efficiency in the tumor. These properties
      maximize the deletion effects on tumor cells. In addition, particle beams can be
      directed precisely in the limit of one or two millimeters, and can be monitored
      using positron emission tomography (PET) with the same precision. In the
      following paper the conditions are given that are necessary to translate these
      properties into clinical routine.

PMID- 9620246
TI  - Number of potential patients to be treated with proton therapy in Italy.
AB  - In radiotherapy, the use of proton beams is one of the most promising approaches
      in order to reduce the treatment volume and, consequently, increase the total
      dose avoiding severe complications to the normal tissues surrounding the target.
      Among the new hospital-based facilities that are planned for the next future, the
      italian project is in an advanced stage of study. Because of the complexity and
      high cost of the italian centre, one of the most important information in order
      to establish the cost/benefit balance, is represented by the number of potential
      patients to be treated for the various pathologies. For this reason it is useful
      to define a priority scale of clinical indications and, on this basis, to
      estimate the yearly patient afflux to the center, taking into account the
      incidence and the expected new cases to be treated with protons. Indications have
      been divided into two categories, according to decreasing priority. Category A
      includes all the tumors in which the use of proton therapy has clearly
      demonstrated to be advantageous, being the only way to give a curative dose to
      the target. In Italy, the estimated number of this category of patients is 825
      each year. Category B comprises a great variety of tumors characterized mainly by
      a local evolution, with a limited likelihood of distant spread, and therefore
      potentially cured if the local control can be obtained. The total number of
      potential patients in this category is more than 10,000.

PMID- 9620247
TI  - Review of current protocols for protontherapy in USA.
AB  - The basis for interest in proton beams by clinical radiation oncologists lies in
      reduction in treatment volume. The yields from employing a smaller treatment
      volume are the increase of tumor control probability and the reduction of normal
      tissues complication probability. The clinical use of proton therapy began in
      1954 at Uppsala University in Sweden and in 1961 at Harvard Cyclotron Laboratory
      in Boston, USA. So far, the total number of worldwide patients treated by protons
      is about 20,000. In this paper attention will be given to the treatment of
      patients at the Massachusetts General Hospital-Massachusetts Eye and Ear
      Infirmary-Harvard Cyclotron Laboratory, and at the Loma Linda University Medical
      Center. In particular, a review of the literature about the techniques and the
      results of treatment of skull base and cervical spine chordoma and low-grade
      chondrosarcoma, skull base meningioma, pituitary tumors, paranasal sinus
      carcinoma, glioblastoma multiforme, artero-venous malformations, uveal melanoma,
      macular degeneration, retinoblastoma, thoracic spine-sacrum tumors, and prostate
      carcinoma is presented. In order to verify and improve the clinical results, the
      conduct of prospective trials on an inter-institutional basis is essential. To
      facilitate the conduct of such studies the US National Cancer Institute and the
      American College of Radiology have established the Proton Therapy Oncology Group
      (PROG). Several phase III and some phase I-II trials are active at the
      Massachusetts General Hospital, Harvard Cyclotron Laboratory, and at the Loma
      Linda University Medical Center.

PMID- 9620248
TI  - Biological and clinical implications for multimodality treatment in patients
      affected by squamous cell carcinoma of the head and neck.
AB  - AIMS AND BACKGROUND: Several strategies combining radiotherapy and chemotherapy
      have been developed for the cure of squamous cell carcinoma of the head and neck
      (SCC-HN) in an attempt to improve loco-regional control and survival. This
      overview aims to summarize clinical results of reported randomized trials and to
      discuss the biological mechanisms underlying the interactive and non-interactive
      processes promoted when chemotherapy is added to radiotherapy. METHODS: The
      clinical goals of combined modality therapy and exploitable associations of
      chemotherapy and radiotherapy that may lead to a therapeutic gain in comparison
      with radiotherapy alone are reported and reviewed. Clinical applications of the
      four main ways of combining chemotherapy with radiotherapy (neoadjuvant,
      concomitant, alternating and adjuvant) are briefly re-analyzed and discussed.
      RESULTS AND CONCLUSIONS: Published evidence suggests that induction chemotherapy
      (neo-adjuvant) should not be routinely recommended; however, induction
      chemotherapy increases the likelihood of larynx preservation in patients with
      laryngeal and hypopharyngeal cancer and should be offered as a treatment option
      as an alternative to surgery. Positive results of several randomized studies and
      a recent meta-analysis show that concomitant use of chemotherapy and radiotherapy
      in unresectable SCC-HN is beneficial and should be considered as a potential
      standard treatment. A complementary biological staging of SCC-HN, by evaluating
      new predictive factors of tumor response, is presently under investigation to
      better interpret clinical randomized trials exploring chemo-radiotherapy.

PMID- 9620249
TI  - Clinical application of integrated treatments in breast cancer.
AB  - In this paper we analyse the problems related to the "state of the art" in the
      treatment of stage I and II breast cancer which has become, in Italy too, an
      increasingly prominent problem: it is the most frequently diagnosed female
      cancer, accounting for about 45,000 new cases/year (150/100,000 women). In the
      last decade the approach to this disease has greatly evolved because of new
      surgical techniques, advances in adjuvant medical therapies, innovations in the
      field of radiotherapy, and wider use of biological parameters. We emphasize the
      emerging problem of ductal and lobular carcinoma in situ, because their
      biological patterns will be better identified and the related treatment
      extensively practiced in the next future. The innovations in surgery, which has
      now a less demolishing role, are reviewed focusing on the "sentinel axillary
      node" and the actual need for axillary dissection. In relation to chemotherapy
      (CT), we evaluate the role of adjuvant treatment also in node negative patients,
      and the impact of neoadjuvant schedules on survival and toxicity. Radiotherapy
      (RT) is complementary to conservative surgery, and its important role in
      preventing local relapse and in increasing OS (overall survival) has been
      established; recent and more sophisticated techniques have reduced its acute and
      late toxicity. We are however waiting for answers concerning the usefulness of a
      booster dose, the impact of RT on local relapse in DCIS, and the impact of RT to
      the breast regional lymph nodes on OS and disease-free survival (DFS). The
      optimal sequencing and timing of postoperative RT and CT are unknown, both
      concerning each other and surgery. Some possibilities include giving all planned
      CT before RT, all CT after RT, giving both concurrently, or giving a portion of
      CT before RT and then completing CT afterwards (sandwich technique): we analyse
      the advantages and the problems of these different therapeutic schedules in
      relation to the OS, the DFS and cosmesis. In conclusion, there are very few
      certainties to guide us in the clinical practice: the general feeling is that we
      need to collect more data on homogeneous groups of patients to better understand
      which are the prognostic factors we can rely on, in order to choose the best
      treatment strategy, and which are the optimal schedules of adjuvant treatments
      (CT and RT), with the aim of improving OS, DFS and cosmesis.

PMID- 9620251
TI  - Radiotherapy combined with other treatments in rectal cancer.
AB  - Since the first reports in the late 1950's, a large amount of data have been
      collected. The analysis of the main evidence from the major randomized trials
      will be analyzed in this paper according to preoperative, postoperative and
      chemoradiation approaches. Fifteen randomized preoperative trials were reported;
      they have been grouped according to the fractionation schedule. In the
      hypofractionation group (5 Gy for fraction), all five studies that delivered 3-5
      doses in one week had a significant improvement in local control and one of them
      also showed improvement in survival. Operative mortality was higher in the
      radiotherapy arm if inadequate techniques had been applied. In 3 out of 8 studies
      with conventional fractionation there was a significant improvement in local
      control, but no impact in survival was detected. No studies with total dose lower
      than 34 Gy had an improvement in local control. None of the six randomized
      postoperative studies showed an improvement in local control or survival. In all
      trials the local control rate was uniform; ranging from 76% to 84%. Toxicity was
      higher in the radiotherapy arm. One preoperative and five postoperative
      randomized studies that used chemoradiation were analyzed. One postoperative
      chemoradiation study showed a significant improvement in survival in comparison
      to the surgery arm, and another showed the same advantage compared to the
      postoperative arm. Protracted infusional administration of 5FU concomitant to
      radiotherapy showed better survival than bolus administration. No advantages were
      shown in using MeCCNU or Levamisole in two studies. Toxicity was high and related
      to the dose and the modality of administration of the drugs in order to
      adequately treat the different stages of rectal cancer, patients must be
      carefully selected in order to prescribe the most effective and the least toxic
      treatment for the individual stage; organ preservation should be an essential
      goal for its impact on quality of life, and the cost estimates should be taken
      into account.

PMID- 9620250
TI  - Neoadjuvant chemotherapy to radiation and concurrent chemoradiation for locally
      advanced squamous cell carcinoma of the cervix: a review of the recent
      literature.
AB  - Radiotherapy is the standard treatment for locally advanced cervical cancer;
      nevertheless it fails to control disease progression within the irradiation
      fields in more than 40% of cases, particularly in patients with bulky tumor.
      Distant metastases are not infrequent in more advanced cases. Chemotherapy has
      been integrated with radiotherapy to improve local control and treat distant
      subclinical metastases. Schedules of combined treatment more frequently
      represented by neoadjuvant chemotherapy followed by radiation (NACT) and by
      concomitant chemotherapy and radiation (CT-RT). A review of the recent literature
      is presented. The role of NACT is controversial: high response rates are reported
      but doubtful advantages in terms of survival or local control have been shown. In
      randomized trials, hydroxyurea concomitant to radiation improves local control
      and survival, particularly in stage IIIB and IVA. Several randomized trials of
      concurrent chemoradiation with 5FU, cisplatin and mitomycin C are underway, but
      few have been published: no significative differences are reported in term of
      local control or survival. Acute toxicity is higher than in radiation alone, but
      usually manageable. For the analysis of late morbidity a longer follow-up is
      required. Large randomized trials of adequate radiotherapy versus concomitant
      chemoradiation are necessary to refine our understanding of the benefits of this
      integrated treatment.

PMID- 9620252
TI  - Radio-chemotherapy of anal cancer.
AB  - Conventional treatment of anal cancer has been the demolitive Miles operation for
      decades. Radiotherapy has been utilized in a limited number of centers for early
      cancers only. Radio-chemotherapy has become the treatment of choice for all
      stages of anal cancer after the first experiences by the group of Detroit and
      after the confirmation of successful results by many other centers. Infusional
      chemotherapy (5-FU and Mitomycin C or CDDP) and concurrent irradiation are able
      to achieve local control in more than 80% of patients. Surgery currently
      represents a rescue treatment for partial responders or in relapsing patients. A
      brief review of the literature and the experience at the Istituto Tumori in
      Milano are presented.

PMID- 9620253
TI  - Radio-chemotherapy of vulvar cancer.
AB  - Surgery alone, more or less demolitive, is the treatment of choice of vulvar
      cancers. Cure rates are high for early cancers only, while locally advanced
      tumors with or without inguinal adenopathies and recurrences have a bad
      prognosis. The excellent results of concurrent chemo-radiotherapy of anal cancers
      suggested to adopt the same approach for locally advanced vulvar cancers. The
      shrinkage of the tumor allowed surgery, often less demolitive than usual, and the
      pathological examination demonstrated an overall complete response in 40% of
      cases. Survival has been improved through this multidisciplinary approach.
      Patients not suitable for surgery obtained important remissions and an improved
      quality of life. Clinical experience at the Istituto Tumori of Milano is
      presented.

PMID- 9620254
TI  - Combined modality treatment for esophageal cancer.
AB  - This paper describes the mechanisms of action of ionizing radiations combined
      with antineoplastic drugs. Some relevant drugs for the combined modality
      treatments of locally advanced lung cancer are reported. The meta-analyses
      including randomized trials comparing single agent (radiotherapy or chemotherapy)
      versus combined chemotherapy and radiotherapy in patients with unresectable non
      small cell lung cancer and limited small cell lung cancer are then reviewed. The
      clinical outcome in relation to different schedules of chemoradiotherapy
      (sequential, alternating and concurrent) is also focussed.

PMID- 9620255
TI  - Combined modality treatment of locally advanced lung cancer.
AB  - This paper describes the mechanisms of action of ionizing radiations combined
      with antineoplastic drugs. Some relevant drugs for the combined modality
      treatments of locally advanced lung cancer are reported. The meta-analyses
      including randomized trials comparing single agent (radiotherapy or chemotherapy)
      versus combined chemotherapy and radiotherapy in patients with unresectable non
      small cell lung cancer and limited small cell lung cancer are then reviewed. The
      clinical outcome in relation to different schedules of chemoradiotherapy
      (sequential, alternating and concurrent) is also focussed.

PMID- 9620256
TI  - The evolving role of radiation therapy in the optimal multimodality treatment of
      childhood cancer.
AB  - Childhood cancer is rare, representing only 1% of the total cancer problem. Of
      children diagnosed with cancer today, more than 70% are predicted to be long-term
      survivors. Essentially all pediatric cancers are treated by interdigitating
      radiation with surgical resection and systemic chemotherapy. The use of
      irradiation, important to achieve high rates of disease local control, must be
      always balanced against late effects specifically related to this treatment
      modality, principally growth retardation and second tumors induction. Using
      neuroblastoma, Wilms' tumor and rhabdomyosarcoma as examples, the advances in the
      optimal multimodality treatment of childhood cancer and the evolution of the role
      of radiation therapy are discussed.

PMID- 9620257
TI  - Prevention of radiotherapy-induced emesis.
AB  - The severity of nausea and vomiting in patients undergoing radiotherapy is lower
      than that associated with chemotherapy regimens, but its duration may be
      considerably longer. Total body irradiation and irradiation of the upper part of
      the abdomen or whole abdomen are considered the most emetogenic regimens in
      radiotherapy. Instead, the emetogenic potential is considered moderate in
      radiotherapy of the thorax, pelvis and lower half-body irradiation, and low in
      radiotherapy of head and neck, extremities, brain and skin. In contrast to the
      very extensive literature on the prevention of chemotherapy-induced emesis,
      relatively few studies have been published on patients submitted to radiotherapy.
      Metoclopramide, prochlorperazine and cannabinoids offer only limited symptom
      control in patients undergoing radiotherapy of moderate to severe emetogenic
      potential. Double-blind randomized studies showed the superior antiemetic
      efficacy of the 5-HT3 antagonists with respect to placebo and to the older
      antiemetic drugs in patients submitted to single dose or fractionated doses of
      radiotherapy to the upper abdomen, to lower hemibody radiotherapy and to total
      body irradiation. In all these cases the 5-HT3 antagonists should be considered
      the antiemetic treatment of choice and should be administered as prophylactic
      agents. The optimal duration of antiemetic therapy with the 5-HT3 antagonists is
      unknown. Whether corticosteroids added to the 5-HT3 antagonists will increase
      their antiemetic efficacy, as in chemotherapy-treated patients, remains to be
      demonstrated in double-blind controlled trials. Patients submitted to
      radiotherapy of low emetogenic risk do not require any antiemetic prophylaxis. In
      this case a rescue antiemetic treatment can be administered if patients present
      vomiting or moderate to severe nausea.

PMID- 9620258
TI  - The multidisciplinary approach in clinical oncology.

PMID- 9620259
TI  - PLATO Treatment Planning System.

PMID- 9620260
TI  - Plant alpha-glucosidases of the glycoside hydrolase family 31. Molecular
      properties, substrate specificity, reaction mechanism, and comparison with family
      members of different origin.

PMID- 9620261
TI  - A diverse family of phenylalanine ammonia-lyase genes expressed in pine trees and
      cell cultures.
AB  - Using degenerate PCR primers that target evolutionarily conserved sequences in
      pal genes, we show that in the gymnosperm, Pinus banksiana, phenylalanine ammonia
      lyase (PAL) is encoded by a multigene family of at least eight to ten loci. Five
      classes of pal sequence were easily distinguished among 28 clones sequenced from
      the products of PCR amplification of haploid genomic DNA. The dominant sequence
      from each class was named, yielding pal1 to pal5 loci. These genes shared 68.8%
      to 94.0% nucleotide identity over the 366 bp region compared. All of pal1 to pal5
      were expressed in cell suspension cultures treated with a fungal elicitor and all
      but pal3 were expressed in differentiating xylem tissue of a mature tree. Only
      pall was expressed in unelicited cell cultures. While these P. banksiana genes
      are quite divergent, they are still more similar to each other than to any
      angiosperm pal gene cloned to date. For its roles in development and defense, PAL
      production in P. banksiana is coordinated from a large, diverse multigene family.
      We discuss evidence suggesting that other pines have similar pal gene family
      structures.

PMID- 9620262
TI  - Intraspecific variability of the tandem repeats in Nicotiana putrescine N
      methyltransferases.
AB  - The putrescine N-methyltransferase (PMT) cDNA clone previously isolated from
      tobacco encodes a spermidine synthase-like protein with an 11 amino acid element
      repeated four times in tandem at the amino terminus. Genomic Southern blot
      analyses indicated that this N-terminal repeat array is found in tobacco PMTs but
      absent in Hyoscyamus and Atropa PMTs. A truncated tobacco PMT in which this
      repeat array was entirely removed still retained full enzymatic activity when
      expressed in Escherichia coli. Three PMT genes (NsPMT1, NsPMT2, NsPMT3) isolated
      from Nicotiana sylvestris encode two, five, and nine tandem repeats,
      respectively, in the first exon, but otherwise encode highly conserved proteins.
      Analysis of PCR fragments amplified from the genomes of N. tabacum and its two
      probable progenitors shows that one of the nine repeat elements in NsPMT3 was
      precisely deleted in the corresponding N. tabacum gene. These results indicate
      that direct tandem repeats of a 33 bp sequence that encodes 11 amino acids of no
      obvious function were added to the ancestral Nicotiana PMT gene, and that the
      tandem repetition was genetically very unstable, contracting or expanding during
      evolution of the Nicotiana species.

PMID- 9620263
TI  - Cytochrome P450 superfamily in Arabidopsis thaliana: isolation of cDNAs,
      differential expression, and RFLP mapping of multiple cytochromes P450.
AB  - We have isolated multiple cDNAs encoding cytochromes P450 (P450s) from
      Arabidopsis thaliana employing a PCR strategy. Degenerate oligonucleotide primers
      were designed from amino acid sequences conserved between two plant P450s,
      CYP71A1 and CYP73A2, including the heme-binding site and the proline-rich motif
      found in the N-terminal region, and 11 putative P450 fragments were amplified
      from first-strand cDNA from 7-day-old Arabidopsis as a template. With these PCR
      fragments as hybridization probes, 13 full-length and 3 partial cDNAs encoding
      different P450s have been isolated from an Arabidopsis cDNA library. These P450s
      have been assigned to either one of the established subfamilies: CYP71B, CYP73A,
      and CYP83A; or novel subfamilies: CYP76C, CYP83B, and CYP91A. The primary protein
      structures predicted from the cDNA sequences revealed that the regions around
      both the heme-binding site and the proline-rich motif were highly conserved among
      all these P450s. The N-terminal structures of the predicted P450 proteins
      suggested that these Arabidopsis P450s were located at the endoplasmic reticulum
      membrane. The loci of four P450 genes were determined by RFLP mapping. One of the
      clones, CYP71B2, was located at a position very close to the ga4 and gai
      mutations. RNA blot analysis showed expression patterns unique to each of the
      P450s in terms of tissue specificity and responsiveness to wounding and
      light/dark cycle, implicating involvement of these P450s in diverse metabolic
      processes.

PMID- 9620264
TI  - Inositide signalling in Chlamydomonas: characterization of a phosphatidylinositol
      3-kinase gene.
AB  - Phosphoinositide (PI) 3-kinases, which phosphorylate the D-3 position of the
      inositol ring, function in several different signalling pathways. The
      phosphatidylinositol (PtdIns)-specific PI 3-kinase of yeast (Vps34p) is part of a
      receptor signalling protein complex associated with the trans-Golgi membranes,
      whereas PI 3-kinases that phosphorylate polyphosphoinositides in animal cells
      form a major receptor-controlled signalling pathway in the plasma membrane.
      Recent studies have indicated the presence of active PLC, PLD, and PI 3-kinase
      dependent signalling systems in the unicellular green alga Chlamydomonas, and
      PtdIns-3P in Chlamydomonas shows a particularly high rate of turnover. Here we
      report the cloning of the Chlamydomonas Vps34p, and some characterisation of its
      properties, regulation and localisation. A single-copy 12 kb gene was present.
      The corresponding protein of 122 kDa had full-length homology with Vps34ps from
      other species, but it contained a novel spacer-like insert region of 148 amino
      acid residues between homology region 2 (HR2) and the C-terminal catalytic core
      domain, and three other shorter putative inserts. Available cDNAs were used to
      assemble a pBluescript clone expressing a recombinant protein which had PtdIns
      specific 3-kinase activity. However, an unexpected observation was that
      recombinant proteins containing the complete catalytic core, but lacking HR2, had
      no lipid kinase activity, pointing to a previously unsuspected role for this
      domain, possibly in substrate binding. VPS34 mRNA and protein levels, as
      determined by RNAse protection assays and by immunological methods respectively,
      were low in all cell stages that were examined. Western blotting of subcellular
      fractions revealed that most of Vps34p in cell lysates of cw-15 (a cell wall
      deficient mutant) could be recovered in a NP-40-resistant 100000 x g pellet,
      suggesting that the enzyme may have a location different from that found in
      higher plants.

PMID- 9620265
TI  - Patterns of ENOD40 gene expression in stem-borne nodules of Sesbania rostrata.
AB  - At the base of adventitious root primordia, located on the stem of the tropical
      legume Sesbania rostrata, nitrogen-fixing nodules are formed upon inoculation
      with the microsymbiont Azorhizobium caulinodans. This pattern of nodule
      development presents features of indeterminate and determinate nodules in early
      and later stages, respectively. A S. rostrata cDNA clone homologous to early
      nodulin ENOD40 genes was isolated from a cDNA library of developing stem nodules.
      SrENOD40-1 contained the conserved regions I and II of other ENOD40 genes. By
      reverse transcriptase PCR, enhanced SrENOD40-1 expression was observed in the
      adventitious root primordia between 4 and 8 h after inoculation with A.
      caulinodans. In situ hybridization showed that SrENOD40-1 transcripts, present
      around the central vascular bundle of the uninfected root primordia, were
      strongly enhanced upon induction of nodule development. De novo SrENOD40-1
      expression was observed in the initiating and growing nodule primordia and around
      vascular bundles. When cell type specification sets in, the expression became
      pronounced in cells derived from the meristematic regions. In other parts of the
      plant, weak SrENOD40-1 expression was associated with vascular bundles and was
      observed in leaf and stipule primordia.

PMID- 9620266
TI  - Characterization of rbcL group IA introns from two colonial volvocalean species
      (Chlorophyceae).
AB  - Group I introns were reported for the first time in the large subunit of Rubisco
      (rbcL) genes, using two colonial green algae, Pleodorina californica and Gonium
      multicoccum (Volvocales). The rbcL gene of P. californica contained an intron
      (PIC intron) of 1320 bp harboring an open reading frame (ORF). The G. multicoccum
      rbcL gene had two ORF-lacking introns of 549 (GM1 intron) and 295 (GM2 intron)
      base pairs. Based on the conserved nucleotide sequences of the secondary
      structure, the PIC and GM1 introns were assigned to group IA2 whereas the GM2
      intron belonged to group IA1. Southern hybridization analyses of nuclear and
      chloroplast DNAs indicated that such intron-containing rbcL genes are located in
      the chloroplast genome. Sequencing RNAs from the two algae revealed that these
      introns are spliced out during mRNA maturation. In addition, the PIC and GM1
      introns were inserted in the same position of the rbcL exons, and phylogenetic
      analysis of group IA introns indicated a close phylogenetic relationship between
      the PIC and GM1 introns within the lineage of bacteriophage group IA2 introns.
      However, P. californica and G. multicoccum occupy distinct clades in the
      phylogenetic trees of the colonial Volvocales, and the majority of other colonial
      volvocalean species do not have such introns in the rbcL genes. Therefore, these
      introns might have been recently inserted in the rbcL genes independently by
      horizontal transmission by viruses or bacteriophage.

PMID- 9620268
TI  - Characterization of a single soybean cDNA encoding cytosolic and glyoxysomal
      isozymes of aspartate aminotransferase.
AB  - A soybean cDNA clone, pSAT1, which encodes both the cytosolic and glyoxysomal
      isozymes of aspartate aminotransferase (AAT; EC 2.6.1.1) was isolated. Genomic
      Southern blots and analysis of genomic clones indicated pSAT1 was encoded by a
      single copy gene. pSAT1 contained an open reading frame with ca. 90% amino acid
      identity to alfalfa and lupin cytosolic AAT and two in-frame start codons,
      designated ATG1 and ATG2. Alignment of this protein with other plant cytosolic
      AAT isozymes revealed a 37 amino acid N-terminal extension with characteristics
      of a peroxisomal targeting signal, designated PTS2, including the modified
      consensus sequence RL-X5-HF. The second start codon ATG2 aligned with previously
      reported start codons for plant cytosolic AAT cDNAs. Plasmids constructed to
      express the open reading frame initiated by each of the putative start codons
      produced proteins with AAT activity in Escherichia coli. Immune serum raised
      against the pSAT1-encoded protein reacted with three soybean AAT isozymes, AAT1
      (glyoxysomal), AAT2 (cytosolic), and AAT3 (subcellular location unknown). We
      propose the glyoxysomal isozyme AAT1 is produced by translational initiation from
      ATG1 and the cytosolic isozyme AAT2 is produced by translational initiation from
      ATG2. N-terminal sequencing of purified AAT1 revealed complete identity with the
      pSAT1-encoded protein and was consistent with the processing of the PTS2.
      Analysis of cytosolic AAT genomic sequences from several other plant species
      revealed conservation of the two in-frame start codons and the PTS2 sequence,
      suggesting that these other species may utilize a single gene to generate both
      cytosolic and glyoxysomal or peroxisomal forms of AAT.

PMID- 9620267
TI  - cDNA cloning and expression analysis of genes encoding GSH synthesis in roots of
      the heavy-metal accumulator Brassica juncea L.: evidence for Cd-induction of a
      putative mitochondrial gamma-glutamylcysteine synthetase isoform.
AB  - In roots of Brassica juncea L. cadmium (Cd) exposure (25 microM) induces a
      massive formation of phytochelatins (PCs), which is accompanied by an only
      moderate decrease (-20%) of the putative PC precursor glutathione (GSH). As PC
      formation in roots could be the result of local GSH de novo synthesis and/or
      depend on GSH import from the shoot, we have analyzed the expression of the
      enzymes involved in GSH synthesis in the root, namely OAS(thiol)lyase (OAS-TL;
      catalysing the last step in Cys biosynthesis), gamma-glutamylcysteine synthetase
      (gamma-ECS), and glutathione synthetase (GSHS). cDNA clones were isolated from a
      cDNA library prepared from heavy metal exposed roots. Protein sequences from cDNA
      clones encoding OAS-TL, gamma-ECS, and GSHS, all exhibited putative mitochondrial
      targeting sequences, however, for OAS-TL also two putative cytosolic isoforms
      were isolated. Furthermore, we have cloned several metallothionein cDNAs of the
      MT2 group. Northern blot analysis with coding region probes revealed that in
      roots of Cd-exposed plants transcript amounts for OAS-TL and GSHS were only
      moderately increased, whereas gamma-ECS mRNA showed a stronger increase.
      Expression analysis with 3'-UTR probes indicated that among the putative
      mitochondrial OAS-TL, gamma-ECS and GSHS isoforms only gamma-ECS was up-regulated
      in response to Cd exposure. Conversely, transcripts for MT2 appeared to be
      slightly reduced. The results indicate that in roots Cd-induced PC synthesis
      correlates with a moderate increase of expression of genes involved in GSH
      synthesis, the change for gamma-ECS being most pronounced.

PMID- 9620269
TI  - Developmentally regulated organ-, tissue-, and cell-specific expression of
      calmodulin genes in common wheat.
AB  - Recently, we reported on the characterization of the calmodulin (CaM) gene family
      in wheat [44]. We classified wheat CaM genes into four subfamilies (SFs)
      designated SF-1 to SF-4, each representing a series of homoeoallelic loci on the
      homoeologous chromosomes of the three genomes of common wheat. Here we studied
      the expression of these wheat CaM genes in the course of wheat development.
      Northern blot analysis using SF-specific probes revealed differences in SF
      expression levels in different organs and stages of development. Subsequently,
      cell-specific expression of CaM SFs was investigated by in situ RNA
      hybridization. In developing seeds, all CaM SFs showed highest expression in the
      embryo and less in the aleurone and in the starchy endosperm. In primary roots,
      all four CaM SFs were expressed in the root cap, meristematic regions and in
      differentiating cells. During development of the roots, expression gradually
      decreased. The wheat glutenin gene, which was used as a control throughout our
      experiments, was found to be expressed in the starchy endosperm but not in the
      aleurone, embryos or vegetative tissues. In stems, at advanced stages of growth,
      differences in cell-specific expression of CaM SFs were found. For example, SF-2
      was highly expressed in differentiating phloem fibers. Thus, CaM genes in common
      wheat exhibit a developmentally regulated organ-, tissue-, cell- and SF-specific
      expression patterns.

PMID- 9620270
TI  - Isolation and characterization of a functional A-type cyclin from maize.
AB  - Cyclins are involved in the regulation of cell cycle progression in eukaryotes.
      We have isolated a cyclin cDNA clone, cycZm2w, from maize root tip cells, which
      fits best into group A2 of current plant cyclin gene classification schemes. The
      cDNA encodes a protein with a domain homologous to the cyclin box of mitotic
      cyclins. Complementation studies revealed that cycZm2w was able to rescue a
      budding yeast cyclin-deficient mutant (BF305-15d#21). As expected, cycZm2w is
      expressed in organs of the maize plant that possess meristematic activity, but is
      especially prominent in the proliferating regions of the root apex.

PMID- 9620271
TI  - Molecular cloning and characterization of an inorganic pyrophosphatase from
      barley.
AB  - A cDNA clone with sequence homology to soluble inorganic pyrophosphatase (IPPase)
      was isolated from a library of developing barley grains. The protein encoded by
      this clone was produced in transgenic Escherichia coli, and showed IPPase
      activity. In nondormant barley grains, the gene appeared to be expressed in
      metabolically active tissue such as root, shoot, embryo and aleurone. During
      inhibition, a continuous increase of the steady state mRNA level of IPPase was
      observed in embryos of non-dormant grains. In the embryos of dormant grains its
      production declined, after an initial increase. With isolated dormant and
      nondormant embryos, addition of recombinant IPPase, produced by E. coli, enhanced
      the germination rate. On the other hand, addition of pyrophosphate (PPi),
      substrate for this enzyme, appeared to reduce the germination rate. A role for
      this IPPase in germination is discussed.

PMID- 9620272
TI  - Maize contains a Lon protease gene that can partially complement a yeast pim1
      deletion mutant.
AB  - We have identified a gene in maize that encodes a product belonging to the Lon
      protease family. In yeast and mammals, Lon-type proteases catalyze the ATP
      dependent degradation of mitochondrial matrix proteins. The maize gene, which we
      have designated LON1, is predicted to encode a protein with a molecular mass of
      97.7 kDa. Lon1p is more similar in sequence to bacterial Lon proteases than to
      the yeast and human mitochondrial Lon proteases. LON1 transcripts are present in
      shoots of 4-day-old etiolated maize seedlings, and transcript levels decrease
      when these seedlings are heat-shocked. LON1 transcripts are also present at
      comparable levels in leaves and roots of 2-week-old greenhouse-grown seedlings.
      In yeast, the mitochondrial Lon-type protease, Pim1p, has been implicated in
      mitochondrial protein turnover, the assembly of mitochondrial enzyme complexes,
      and mitochondrial DNA maintenance, and it is essential for respiratory function.
      We show that maize Lon1p can replace the Pim1p function in yeast for maintaining
      mitochondrial DNA integrity, but not in the assembly of cytochrome a x a3
      complexes.

PMID- 9620274
TI  - The light-regulated Arabidopsis bZIP transcription factor gene ATB2 encodes a
      protein with an unusually long leucine zipper domain.
AB  - A light-regulated basic domain/leucine zipper gene, ATB2, was identified in an
      Arabidopsis thaliana transcription factor gene collection. Both genomic and cDNA
      clones of ATB2 were isolated. The gene encodes a small protein (18 kDa) which
      mainly consists of the basic domain and an unusually long leucine zipper. The
      expression of the ATB2 gene is induced when etiolated or dark-adapted seedlings
      are transferred to the light. Moreover, its expression is derepressed in dark
      grown seedlings of the photomorphogenic mutants cop1 and det1. In mature plants,
      transcript levels are particularly high in flowers and also light-responsive in
      these tissues.

PMID- 9620275
TI  - Isolation, characterisation and expression of a cDNA for pea cholinephosphate
      cytidylyltransferase.
AB  - In plants, phosphatidylcholine is the major phospholipid in extra-plastid
      membranes and is synthesised mainly by the CDP-choline pathway. Evidence from
      studies in animals, as well as in plants, suggests that the intermediate step
      catalysed by cholinephosphate cytidylyltransferase (CPCT) has a major control in
      carbon flux to this lipid. We have isolated a full-length CPCT cDNA (designated
      PCT2) from Pisum sativum cv. Feltham First using an Arabidopsis probe and the
      polymerase chain reaction (PCR). The deduced amino acid of PCT2 is 48%, 43% and
      76% identical to the rat, yeast and Brassica napus amino acid sequences,
      respectively. Expression of the CPCT protein in Escherichia coli confirmed the
      activity of the enzyme. Expression of the PCT2 mRNA in pea roots and stems was
      increased by treatment with 0.1 microM indole-3-acetic acid.

PMID- 9620273
TI  - The maize retinoblastoma protein homologue ZmRb-1 is regulated during leaf
      development and displays conserved interactions with G1/S regulators and plant
      cyclin D (CycD) proteins.
AB  - Recent discoveries of plant retinoblastoma (Rb) protein homologues and D-type
      cyclins suggest that control of the onset of cell division in plants may have
      stronger parallels with mammalian G1/S controls than with yeasts. In mammals, the
      Rb protein interacts specifically with D-type cyclins and regulates cell
      proliferation by binding and inhibiting E2F transcription factors. However, the
      developmental role of Rb in plants and its potential interaction with cell cycle
      regulators is unknown. We show that the maize Rb homologue ZmRb-1 is temporally
      and spatially regulated during maize leaf development. ZmRb-1 is highly expressed
      in differentiating cells, but almost undetectable in proliferating cells. In
      vitro, both ZmRb-1 and human Rb bind all classes of plant D-type cyclins with the
      involvement of a conserved N-terminal Leu-x-Cys-x-Glu (LxCxE) Rb-interaction
      motif. This binding is strongly reduced by mutation of the conserved Cys-470 of
      ZmRb-1. ZmRb-1 binds human and Drosophila E2F, and inhibits transcriptional
      activation of human E2F. We also show that ZmRb-1 is a good in vitro substrate
      for all human G1/S protein kinases. The functional conservation of proteins that
      control the G1/S transition in mammals and plants points to the existence of
      plant E2F homologues. We conclude that evolution of Rb and cyclin D proteins
      occurred after separation of the fungi from the higher eukaryotic lineage, but
      preceded the divergence of plant and animal kingdoms.

PMID- 9620277
TI  - Whiteness of Worcester.

PMID- 9620276
TI  - A maize pectin methylesterase-like gene, ZmC5, specifically expressed in pollen.
AB  - Pectin methylesterase (PME) is responsible for the demethylation of pectin prior
      to pectin's degradation by the combined activities of polygalacturonase and
      pectate lyase. We have differentially screened a maize pollen cDNA library to
      detect cDNA clones whose genes are specifically expressed in pollen. One group of
      clones resulting from this screen showed similarity (between 18% and 41%
      identity) with plant and fungal PMEs. The full-length clone from this group,
      ZmC5, identifies a small gene family (at least 2 members) when used as a probe on
      genomic Southern blots. Northern analysis reveals that the ZmC5 transcript is
      expressed specifically in late pollen development. This tissue-specific gene
      expression programme is further confirmed in transgenic tobacco plants harbouring
      ZmC5 promoter/GUS chimeric gene constructs.

PMID- 9620278
TI  - Separate regulation of peripheral hematopoietic and thymic engraftment.
AB  - Long-term multilineage chimerism, indicating pluripotent hematopoietic stem cell
      engraftment, was achieved in an Ly5-congenic strain combination without
      irradiation or other host conditioning when a large number of donor marrow cells
      (1.4-2x10(8)) was administered. However, the initial (2-4 weeks
      posttransplantation) percentages of T and B lymphocytes of donor origin were
      markedly lower than those of myeloid lineages. Steady-state levels of donor and
      host repopulation of all lineages were reached by 7 to 15 weeks
      posttransplantation and remained relatively constant for at least 41 weeks. B
      cell chimerism was similar to that seen in myeloid lineages at steady state. In
      contrast, long-term donor representation in the T cell lineage was much lower
      than in the B cell or myeloid lineages. Host treatment with depleting anti-T cell
      monoclonal antibodies increased the donor contribution to early T cell
      repopulation, but long-term T cell chimerism was still significantly lower in all
      lymphohematopoietic tissues, including the thymus, than B cell or myeloid cell
      chimerism. Pretreatment of hosts with 3.5 Gy of local irradiation to the thymic
      region further increased the donor contribution to initial T cell repopulation,
      which equaled that of other lineages at 4 to 7 weeks. However, donor
      representation in the T cell lineage declined by the time steady-state chimerism
      was attained and was lower than donor representation in the B cell or myeloid
      lineages. A higher dose of thymic irradiation (7 Gy) led to a reduction in this
      discrepancy, so that levels of donor thymopoiesis and hematopoiesis in other
      lineages were similar by 23 to 27 weeks posttransplantation. The differential
      contribution of adult donor marrow to long-term, steady-state thymopoiesis vs.
      hematopoiesis in other lineages under certain conditions in this competitive
      repopulation assay suggests that functionally distinguishable progenitors are
      responsible for these activities.

PMID- 9620279
TI  - Menadione induces changes in the membrane electrical properties associated with
      downregulation of insulin receptors in human erythrocytes.
AB  - We have demonstrated using dielectric relaxation measurements in the
      radiofrequency range that the electrical properties of human erythrocytes
      (membrane conductivity and permittivity as well as the conductivity of the
      cytosol) undergo a steady decrease over time during insulin-induced
      downregulation of insulin receptors (Santini et al., Experimental Hematology
      22:40-44, 1994). In the present paper, we show that exposure of these
      erythrocytes to the strong oxidizing agent menadione before addition of insulin
      blocks insulin receptor internalization as well as the decrease in electrical
      parameters associated with this process. We hypothesize that menadione blocks
      internalization of these receptors by inducing oxidative damage on the
      erythrocytes and, consequently, disrupting the normally occurring variations in
      electrical parameters. This postulate was confirmed by addition of the
      antioxidant N-acetylcysteine to menadione-treated cells, in which a return to the
      original changes in electrical parameters noted in untreated cells was observed.

PMID- 9620280
TI  - Recombinant murine (rm) interleukin (IL)-5 enhances the eosinophil peroxidase
      content in cells cultured in vitro compared with rmIL-3 and granulocyte
      macrophage colony-stimulating factor.
AB  - We previously reported an in vitro bioassay permissive to eosinophil production
      from naive mouse bone marrow cells. Based on cytosmear analysis, recombinant
      murine (rm) interleukin (IL)-3 combined with granulocyte-macrophage colony
      stimulating factor (GM-CSF) provided better quantitative cellular yields compared
      with rmIL-5. In the present study, we compared the eosinophil peroxidase (EPO)
      content obtained in both in vitro conditions using microtitration. Parallel with
      the EPO assay, the percentage of eosinophils present in cultures was determined
      by cytosmear analysis. Cells incubated with IL-5 displayed significantly higher
      EPO activity than those cultured in the presence of IL-3 and GM-CSF. At the end
      of the culture period, cells were further enriched in eosinophils as determined
      by centrifugation gradient. Enhanced amounts of cellular EPO were detected when
      cultures were performed in the presence of IL-5. With regard to the correlation
      between eosinophil maturation and EPO acquisition, eosinophil cells cultured with
      rmIL-5 expressed significantly more EPO activity than those generated in the
      presence of rmIL-3 and GM-CSF.

PMID- 9620281
TI  - Flt3/Flk-2 and c-Kit are not essential for the proliferation of B lymphoid
      progenitor cells in the bone marrow of the adult mouse.
AB  - The receptor tyrosine kinase Flk-2/Flt3 was originally cloned from hematopoietic
      stem cell-enriched fetal liver and placenta and is believed by some investigators
      to play a role in the regulation of the hematopoietic stem cell. However,
      targeted disruption of the flt3 gene results in a specific deficiency in early B
      cell progenitors. Using an antagonistic monoclonal antibody developed against the
      extracellular domain of Flt3, we investigated the expression and function of the
      molecule on B lymphoid lineage cells in the bone marrow (BM) of adult mice.
      Approximately 10% of B220+ cells in the BM expressed Flt3 on the cell surface,
      and most of the cells belonged to a pro-B cell fraction when judged by an
      expression pattern of CD43, heat-stable antigen, and BP-1. However, B lymphoid
      precursor cells that are clonable in vitro could not be enriched in the
      B220+/Flt3+ cell fraction sorted by flow cytometry. Furthermore, proliferation of
      B lymphoid precursor cells in the adult BM was not blocked by administration of
      the antagonistic monoclonal antibodies against Flt3 and c-Kit, suggesting that
      signalings mediated by Flt3 and c-Kit receptors are not essential for the
      proliferation of B cell progenitors in adult mouse BM.

PMID- 9620282
TI  - A serum-free culture model for studying the differentiation of human dendritic
      cells from adult CD34+ progenitor cells.
AB  - The antigen-presenting capacity of dendritic cells (DCs) makes them attractive
      potential cellular adjuvants for vaccination strategies. Currently, most in vitro
      culture systems for the production of these DCs include serum. However, this is
      undesirable because serum contains growth factors that vary between individuals
      and could affect DC development. Unless the patient's own serum is used, foreign
      antigens and the risk of infection will detract from the usefulness of these
      cells in clinical strategies. In this study we investigated the production of DCs
      from CD34+ progenitor cells of cancer patients or normal donors under serum-free
      conditions. We have established a model system for the investigation of DC
      development and maturation. Dendritic cells that developed from myeloid
      precursors accumulated after 2 weeks in an intermediate CD1a , CD80-, CD83-, CD86
      stage. Intermediate DCs adhered to plastic surfaces, expressed Birbeck granules,
      and were negative for CD2 and CD14. In the presence of granulocyte-macrophage
      colony-stimulating factor and tumor necrosis factor-alpha, interleukin-4 promoted
      the development of these stages. Spontaneous maturation of intermediate DCs into
      fully activated DCs expressing CD83 and costimulatory molecules occurred
      asynchronously over the ensuing 2 to 3 weeks. This maturation involved increased
      expression of CD80, CD83, CD86, CMRF-44, HLA-A, -B, -C, and -DR as well as
      downregulation of CD1a and CD11b. Activated DCs are characterized by the lack of
      adherence to plastic surfaces and the absence of Birbeck granules. By day 28,
      these cells were nonphagocytic, potent antigen-presenting cells with an
      irreversible phenotype. This serum-free system offers advantages in that the
      process of differentiation and maturation of committed DCs is extended over a
      period of more than 28 days, allowing investigators to study the effects of
      individual cytokines or other supplements during distinct phases of DC
      development in a defined environment.

PMID- 9620283
TI  - All-trans retinoic acid modulates Fas antigen expression and affects cell
      proliferation and apoptosis in combination with anti-Fas monoclonal antibody in
      the human myeloma cell line, U266B1.
AB  - All-trans retinoic acid (ATRA) is a vitamin A derivative that induces the
      differentiation of myeloid leukemia cells in vitro and in vivo. Several
      investigators have recently reported that ATRA downregulates the production of
      interleukin-6 (IL-6) and the expression of IL-6 receptor (IL-6R) and also
      inhibits the proliferation of myeloma cells. It has also been reported that
      myeloma cells express Fas antigen, and in some of these cells apoptosis was
      induced by treatment with anti-Fas monoclonal antibody (mAb). In the present
      study, we demonstrated that ATRA increased Fas expression in the human myeloma
      cell line, U266B1. We observed that both apoptosis induction and growth
      inhibition were enhanced in cells exposed to a combination of anti-Fas mAb and
      ATRA compared with cells exposed to either treatment alone. We also examined
      whether ATRA modulated bcl-2, an anti-apoptosis protein, in U266B1 cells. Flow
      cytometry analysis revealed that the mean fluorescence intensity of bcl-2 protein
      was slightly decreased in cells treated with ATRA. These results indicate that in
      U266B1 cells, combined treatment with anti-Fas mAb and ATRA enhances the
      induction of apoptosis by modulating the expression of Fas and bcl-2 by ATRA.

PMID- 9620284
TI  - Engraftment of ex vivo expanded and cycling human cord blood hematopoietic
      progenitor cells in SCID mice.
AB  - The ability of human hematopoietic cells to engraft SCID mice provides a useful
      model in which to study the efficiency of retroviral gene transfer and expression
      in primitive stem cells. In this regard, it is necessary to determine whether
      SCID mice can be engrafted by cycling human hematopoietic progenitor cells. Human
      cord blood cells from 12 different donors were cultured in vitro for 6 days with
      interleukin-3 and stem cell factor. Phenotypic analysis indicated that
      hematopoietic cells were induced to cycle and the number of progenitors was
      expanded, thus making them targets for retroviral gene transfer. The cells were
      then transferred to SCID mice. Human hematopoietic progenitor cell engraftment
      was assessed up to 7 weeks later by growth of human progenitor cells in soft
      agar. After in vitro culture under conditions used for retroviral gene transfer,
      human cord blood hematopoietic cells engrafted the bone marrow and spleen of SCID
      mice. Interestingly, cultured cord blood cells engrafted after intraperitoneal
      but not after intravenous injection. Furthermore, engraftment of cord blood cells
      was observed in mice receiving no irradiation before transfer of the human cells,
      suggesting that competition for space in the marrow is not a limiting factor when
      these cells have been cultured. Administration of human cytokines after transfer
      of human cord blood cells to SCID mice was also not required for engraftment.
      Thus, engraftment of SCID mice with human hematopoietic cells cultured under
      conditions suitable for gene transfer may provide an in vivo assay for gene
      transfer to early human hematopoietic progenitor cells.

PMID- 9620285
TI  - Radioprotective effects of flk2/flt3 ligand.
AB  - The radioprotective properties of flk2/flt3 ligand (FL) were evaluated in
      lethally irradiated mice. Optimum survival rates (70-80%) were observed when 5 to
      20 microg of FL was administered at both 20 and 2 hours before LD100/30
      radiation. Administration of FL well in advance of irradiation was essential for
      conferring most of the radioprotection, since a single dose given at -20 hours
      still resulted in a significant survival rate (65%), whereas a single dose given
      at -2 hours was relatively nonprotective. Histopathologic examination at 7 and 9
      days postirradiation revealed significant myelopoietic activity in the bone
      marrow (BM) of FL-treated mice, suggesting that their survival might be due to
      sparing of radiosensitive hematopoietic cells. By comparison, the BM of mice
      treated with phosphate-buffered saline was extremely hypocellular and remained
      that way until they died of bacterial infection. Hematopoietic assays confirmed a
      marked stimulation of early white blood cell (WBC) recovery in the BM and blood
      of FL-protected mice relative to PBS-treated controls. By day 21, FL-protected
      mice showed circulating WBC numbers that were higher than preirradiation values;
      however, their BM colony-forming units in culture were still depressed. Moreover,
      these mice experienced a prolonged anemia and thrombocytopenia. These findings
      are discussed in light of the restricted subset of hematopoietic progenitors
      shown to be responsive to FL in vitro.

PMID- 9620286
TI  - Distinct circadian time structures characterize myeloid and erythroid progenitor
      and multipotential cell clonogenicity as well as marrow precursor proliferation
      dynamics.
AB  - Circadian differences in the susceptibility of the marrow to the effects of
      radiation, myelotoxic drugs, and growth factors suggest that hematopoietic
      processes vary significant throughout each day. One mechanism possibly
      responsible for the differing degrees of marrow damage sustained from a fixed
      dose of a cytotoxic agent at different times of day is the circadian organization
      of cell cycle events. Previous circadian rhythm-oriented studies of proliferation
      using unfractionated marrow have reported seemingly contradictory peak and nadir
      times of day. Marrow represents a heterogeneous population of stem cells and
      various hematopoietic progenitors whose proliferation and differentiation are
      controlled by both common and unique factors. Therefore, we examined lineage
      specific circadian marrow proliferative dynamics for evidence of parasynchronous
      circadian DNA synthesis. Cell cycle phase was determined using flow cytometry
      with both propidium iodide staining and 5-bromo-2'-deoxyuridine (BrdU)
      incorporation concurrently with cell culture-based determinations of lineage
      specific progenitor numbers in the same marrow samples. Although no clear
      circadian (24-hour) rhythm characterized unfractionated marrow DNA synthesis,
      both erythroid- and myeloid-enriched subpopulations demonstrated distinct
      circadian patterns with respect to the percentage of cells incorporating BrdU,
      with up to 50% differences throughout each day. Interestingly, these circadian
      rhythms in erythroid and myeloid progenitor cell DNA synthesis are entirely
      different from one another. The lineage-specific circadian patterns in the
      fraction of cells undergoing DNA synthesis are, in part, paralleled by up to
      eightfold larger circadian differences in erythroid and myeloid colony numbers.
      Multipotential colony numbers likewise vary throughout the day, with a unique
      pattern of their own. The predominant period length of daily rhythms in colony
      numbers and their amplitudes differ as a function of the stage of progenitor
      commitment. Multipotent and early progenitor colony numbers each exhibit 24-hour
      rhythms, with three- to fivefold daily peak-trough differences, whereas later
      progenitor colony numbers exhibit two peaks per day (12-hour rhythms) with
      twofold peak-trough differences throughout each day. In vivo erythropoietin (Epo)
      administration enhances daily rhythms in erythroid colony numbers by increasing
      their amplitudes while leaving their circadian shapes virtually unchanged. The
      increment in erythroid colony numbers after Epo administration varies up to 16
      fold with the time of day of treatment. In summary, we have defined distinctly
      different lineage-dependent circadian patterns of marrow progenitor numbers and
      proliferating cells. We can infer from these data that the circadian timing of
      administration of physical, chemical, or biologic agents, whose bioactivity
      toward marrow precursors depends on the cell cycle phase of its presentation, can
      be expected to affect this activity predictably and significantly. These results
      may have practical applications in improving stem and progenitor cell yields by
      optimal circadian timing of growth factor administration and harvest.

PMID- 9620287
TI  - Construction of temperature and Zn-dependent human stromal cell lines that
      amplify hematopoietic precursors from cord blood CD34+ cells.
AB  - Forty-five human stromal cell lines were established from long-term bone marrow
      cultures transformed with a new vector, pNu MTSVts, which contains the Zn
      inducible metallothionein promoter and the temperature-dependent SV40 T antigen
      from SV40 A58 mutant. Six of these cell lines were studied because of their
      growth capacity. All cell lines differed with respect to growth potential,
      expression of cell surface markers, and cytokine transcripts. Major
      histocompatibility complex (MHC) class I, CD29, CD49d, and CD51 were present on
      all stromal cell lines, MHC class II and CD34 were consistently absent, and CD11a
      (LFA-1), CD18 (ICAM-1R), CD54 (ICAM-1), CD58 (LFA-3) CD56 (N-CAM), CD106 (V-CAM),
      laminin, and collagen IV were diversely expressed. All cell lines contained
      interleukin (IL)-1alpha, IL-1beta, IL-2, IL-5, and macrophage colony-stimulating
      factor (M-CSF) transcripts, whereas granulocyte M-CSF, TNFalpha, IL-3, IL-4, and
      IL-7 were diversely expressed. The most characteristic feature of these cells was
      their varying capacity to expand cord blood CD34+ cells. One of these stromal
      cell lines ensured more than twofold expansion of the initial CD34+CD10-CD19-
      population in the first 2 weeks. Differentiation toward the B cell lineage was
      limited, producing only very small numbers of CD19+ cells after 6 weeks of
      culture.

PMID- 9620288
TI  - Genetic analysis of male pattern baldness and the 5alpha-reductase genes.
AB  - Genetic predisposition and androgen dependence are important characteristics of
      the common patterned loss of scalp hair known as male pattern baldness. The
      involvement of the 5alpha-reductase enzyme in male pattern baldness has been
      postulated due to its role in the metabolism of testosterone to
      dihydrotestosterone. There are two known isozymes of 5alpha-reductase. Type I has
      been predominantly localized to the skin and scalp. Type II, also present on the
      scalp, is the target of finasteride, a promising treatment for male pattern
      baldness. We conducted genetic association studies of the 5alpha-reductase enzyme
      genes (SRD5A1 on chromosome 5 and SRD5A2 on chromosome 2) using dimorphic
      intragenic restriction fragment length polymorphisms. From a population survey of
      828 healthy families comprising 3000 individuals, we identified 58 young bald men
      (aged 18-30 y) and 114 older nonbald men (aged 50-70 y) for a case control
      comparison. No significant differences were found between cases and controls in
      allele, genotype, or haplotype frequencies for restriction fragment length
      polymorphisms of either gene. These findings suggest that the genes encoding the
      two 5alpha-reductase isoenzymes are not associated with male pattern baldness.
      Finally, no clear inheritance pattern of male pattern baldness was observed. The
      relatively strong concordance for baldness between fathers and sons in this study
      was not consistent with a simple Mendelian autosomal dominant inheritance. A
      polygenic etiology should be considered.

PMID- 9620289
TI  - Reduced stability and bi-allelic, coequal expression of profilaggrin mRNA in
      keratinocytes cultured from subjects with ichthyosis vulgaris.
AB  - Ichthyosis vulgaris (IV) is an inherited scaling skin disorder in which
      expression of profilaggrin is reduced. Previous studies have indicated that the
      reduction is caused by defective post-transcriptional control of gene expression.
      Here we present evidence that profilaggrin mRNA in keratinocytes cultured from
      subjects with IV is intrinsically unstable and has a shorter half-life compared
      with that in normal cells. When IV-affected keratinocytes were treated with the
      protein synthesis inhibitor cycloheximide, the steady-state level of profilaggrin
      mRNA was increased due to stabilization of the transcript. In addition, the
      number of filaggrin repeats within the profilaggrin gene was studied. The number
      of filaggrin repeats (10-12) in individuals with IV did not differ from that of
      unaffected subjects. Expression of the gene was bi-allelic and coequal in both
      control and affected individuals. Our results suggest a model in which a labile
      ribonuclease and a stabilizing factor may modulate the profilaggrin mRNA steady
      state level in normal cells, whereas the stabilizing factor may be absent or
      functionally inactive in IV-affected keratinocytes.

PMID- 9620290
TI  - Subcellular distribution of tight junction-associated proteins (occludin, ZO-1,
      ZO-2) in rodent skin.
AB  - Occludin is an integral membrane protein that is concentrated at tight junctions
      (zonulae occludentes) in simple epithelial cells. ZO-1 and ZO-2 are peripheral
      membrane proteins that are localized at tight junctions in simple epithelial
      cells and at cadherin-based adherens junctions in nonepithelial cells. In this
      study, we investigated the expression and subcellular distribution of occludin,
      ZO-1, and ZO-2 in rodent skin. Immunoblotting detected all of these molecules in
      isolated epidermis, but the occludin/ZO-1 (or occludin/ZO-2) ratio was
      significantly lower than that in cultured simple epithelial cells. In the
      epidermis of adult skin, occludin was concentrated at cell-cell borders only in
      the most superficial zone of the granular cell layer, whereas ZO-1 and ZO-2 were
      distributed in a much broader zone from the spinous to the granular layers.
      During mouse skin development, this peculiar distribution of occludin in the
      epidermis appeared when the periderm, a simple epithelium bearing typical
      occludin-based tight junctions, was sloughed off at embryonic day 16.5 of
      gestation. Freeze-fracture electron microscopy identified the so-called focal
      strands or maculae occludentes, i.e., spot tight junction-like structures,
      between adjacent granular cells, and anti-occludin monoclonal antibody
      exclusively labeled these focal strands. In hair follicles, occludin and ZO-1
      were colocalized at cell-cell borders in Henle's layer and the cornifying cuticle
      of the inner root sheath. In addition, ZO-1 but not occludin were localized
      weakly at the outer root sheath and intensely at the hair cortex/matrix.

PMID- 9620291
TI  - Ex vivo and in vivo adenovirus-mediated gene therapy strategies induce a systemic
      anti-tumor immune defence in the B16 melanoma model.
AB  - The efficacy of adenovirus-mediated gene therapy for treatment of metastatic B16
      melanomas, established in syngeneic C57BL/6 mice, was assessed via an ex vivo
      cytokine vaccine approach or via an in vivo strategy utilizing combination
      cytokine/herpes simplex virus-thymidine kinase (HSV-tk) suicide gene delivery and
      treatment with ganciclovir (GCV). In the ex vivo tumor vaccine approach, B16
      melanoma cells, transduced in vitro by adenovirus containing either interleukin
      (IL)-2, granulocyte-macrophage colony stimulating factor (GM-CSF), or tumor
      necrosis factor-alpha cytokine genes and gamma irradiated, were subcutaneously
      injected into the flank and a distant subcutaneous challenge injection of
      unmodified B16 melanoma cells was performed 15 d later. Significant reductions in
      challenge tumor volume were observed in the IL-2 group (75% reduction; p = 0.02)
      and in the GM-CSF group (88% reduction; p = 0.0006), whereas the effect for tumor
      necrosis factor-alpha was not statistically significant. In the in vivo treatment
      of established melanomas, this cytokine approach was combined with a suicide gene
      therapy and subcutaneous B16 melanomas were directly injected with (i) IL
      2/recombinant, replication-deficient adenovirus (adv) and thymidine kinase
      (tk)/adv, (ii) GM-CSF/adv, IL-2/adv, and tk/adv, or (iii) control beta
      galactosidase (beta-gal)/adv and tk/adv. After intraperitoneal application of GCV
      (10 mg per kg) for 6 d, the residual tumor masses were excised and the animals
      challenged with unmodified B16 cells. Challenge tumor growth was reduced by 56%
      for the IL-2/tk/adv/GCV treatment (p = 0.041) and by 77% for the GM-CSF/IL
      2/tk/adv/GCV treatment p (p = 0.037), in comparison with the beta-gal/tk/GCV
      control group. These data may hold significant promise for the development of
      effective ex vivo and in vivo gene therapy modalities to counter the highly
      metastatic nature of human melanoma.

PMID- 9620292
TI  - MAP kinase abnormalities in hyperproliferative cultured fibroblasts from
      psoriatic skin.
AB  - Several studies indicate that dermal fibroblasts have a specific role in the
      pathophysiology of psoriasis. We have previously found that cultured fibroblasts
      from psoriatic patients are hyperproliferative and have low cyclic AMP-dependent
      protein kinase activity. In this study, we observed that these cells are also
      larger than normal. Given the key role of mitogen-activated protein kinases
      (MAPK) in the regulation of cell proliferation and cytoskeleton function, we
      characterized MAPK in psoriatic fibroblasts and in normal fibroblasts. Serum and
      platelet-derived growth factor treatment of serum-deprived fibroblasts led to a
      larger increase in MAPK activity in psoriatic cells than in normal cells. We then
      purified MAPK by ion-exchange chromatography. MAPK activity was again found to be
      significantly higher in psoriatic fibroblasts than in normal cells, both when
      deprived of serum (p < 0.01) and when stimulated with serum (p < 0.05).
      Interestingly, 8-bromo-cAMP treatment inhibited serum-stimulated MAPK
      phosphorylation in normal fibroblasts but had no effect in psoriatic fibroblasts.
      We observed a temporal variation in nuclear localization of phosphorylated MAPK
      in cultured fibroblasts stimulated by either serum or platelet-derived growth
      factor. No difference in the localization of phosphorylated MAPK in normal and
      psoriatic skins was found. Psoriatic fibroblasts are the first example of a MAPK
      pathway abnormality in large human benign hyperproliferative cells.

PMID- 9620293
TI  - Differences in age, site distribution, and sex between nodular and superficial
      basal cell carcinoma indicate different types of tumors.
AB  - Basal cell carcinomas (BCC) are among the most common cancers in white subjects.
      Etiologic factors include ultraviolet and ionizing radiation, chemical
      carcinogens, and possibly infection with human papillomaviruses. Because of
      clinical and histologic differences, differential pathogenetic mechanisms have
      been suggested for different BCC subtypes. We studied the patient and tumor
      characteristics of all BCC diagnosed and/or treated at the departments of
      Dermatology and Plastic Surgery of our hospital between 1985 and 1996, and a
      review of the literature was carried out. Some important differences between
      patients with nodular BCC and patients with superficial BCC were observed. The
      frequency of superficial BCC was higher in females and was seen in younger
      patients as compared with nodular BCC. The latter occurred mainly in the
      head/neck region: in males they were seen more frequently on the ears, and in
      females they were predominantly seen on the eyelids, the lips, and in the neck.
      Superficial BCC occurred mainly on the trunk, and occurred significantly more
      often on the trunk in males than in females, where the legs were the most common
      site. These findings strongly suggest that the superficial subtype is a separate
      group within the clinical entity of BCC. Furthermore, our findings seem to
      support the etiologic role of sun exposure in these tumors; however, this role
      may be different for each subtype. Chronic sun exposure may be an etiologic
      factor in nodular BCC as compared with intermittent sun exposure in superficial
      BCC. Other factors, such as differences in site specific host factors and
      referral bias, may also play a role in the differences found between the
      subtypes.

PMID- 9620294
TI  - Identification of mutations in the human PATCHED gene in sporadic basal cell
      carcinomas and in patients with the basal cell nevus syndrome.
AB  - Mutations in PATCHED (PTC), the human homolog of the Drosophila patched gene,
      have been identified in most exons of the gene in patients with the basal cell
      nevus syndrome and in sporadic basal cell carcinomas. We have screened the 23 PTC
      exons for mutations using single strand conformation polymorphism analysis of DNA
      from 86 basal cell nevus syndrome probands, 26 sporadic basal cell carcinomas,
      and seven basal cell nevus syndrome-associated basal cell carcinomas. This screen
      identified mutations located in eight exons in 13 of the basal cell nevus
      syndrome patients and in three of the tumors. The most common mutations were
      frameshifts resulting in premature chain termination. These results provide
      further evidence for the crucial role of PTC as a tumor suppressor in human
      keratinocytes.

PMID- 9620295
TI  - In situ expression of platelet-activating factor (PAF)-receptor gene in rat skin
      and effects of PAF on proliferation and differentiation of cultured human
      keratinocytes.
AB  - Platelet-activating factor (PAF) is a potent lipid mediator that exhibits
      versatile biologic activities in many diverse systems by binding to a specific
      cell-surface receptor (PAFR). Although the production of PAF in cultured
      keratinocytes and fibroblasts has been reported, physiologic roles of this
      mediator in skin remain unclear. In this study, we examined in situ expression of
      PAFR gene in rat skin and the effects of PAF on the proliferation and
      differentiation of cultured human keratinocytes. In rat epidermis, PAFR mRNA
      expression was found from the basal cells to the granular cells, and strong
      signals were seen in the stratum spinosum. In cultured human keratinocytes, a 3.8
      kb PAFR mRNA expression was demonstrated by northern blotting, and two distinct
      type transcripts driven by different promoters were detected by reverse
      transcriptase polymerase chain reaction analysis. Addition of PAF (30-100 nM) to
      cultured keratinocytes during a growth phase inhibited the proliferation. This
      effect was receptor dependent, because the inhibition was completely blocked by a
      PAFR antagonist, WEB 2086 (100 nM). On the other hand, whereas PAF (30-100 nM)
      alone did not affect the cornified envelope formation during the process of
      keratinocyte differentiation, WEB 2086 (30-300 nM) accelerated it in a
      concentration-dependent manner. Addition of PAF (100 nM) reversed the effect of
      WEB 2086, suggesting that WEB 2086 induced cornification by inhibiting PAF
      endogeneously produced by keratinocytes in an autocrine manner. Thus, we propose
      that PAF is an intrinsic regulator of keratinocyte during proliferation and
      differentiation.

PMID- 9620296
TI  - Characterization of the cutaneous exanthem in macaques infected with a Nef gene
      variant of SIVmac239.
AB  - The molecularly cloned viruses known as SIVmac239/R17Y and SIVmac239/YEnef cause
      extensive lymphocyte activation and induce an acute disease syndrome in macaque
      monkeys. One manifestation of this syndrome is a severe diffuse cutaneous
      maculopapular exanthem that is similar to the exanthem associated with HIV-1
      infection. To examine the pathogenesis of this exanthem, biopsies obtained
      throughout the course of clinically evident rash were examined for the presence
      of virus by in situ hybridization and immunohistochemistry, and the cellular
      infiltrate was characterized with respect to cellular immunophenotype and
      chemokine receptor expression. The onset of rash was associated with abundant
      simian immunodeficiency virus nucleic acid and protein within perivascular dermal
      infiltrates and occasionally within intraepithelial cells. Analysis of cellular
      infiltrates showed that biopsies, obtained on the day of rash onset, were
      composed of equal numbers of CD4+ and CD8+ lymphocytes and abundant alphaEbeta7
      positive cells surrounding vessels with upregulated endothelial E-selectin.
      Moreover, by examining virus expression in sequential skin biopsies from the same
      animal, the clearance of virus and the resolution of rash were associated with an
      increase in the percentage of cells expressing CD8, the chemokine receptor CXCR3,
      and GMP-17, a marker of cytotoxic granules. These results suggest that activated
      cytotoxic T cells are trafficking to sites of inflammation in the skin and
      directly or indirectly affect levels of viral replication at these sites.

PMID- 9620297
TI  - Towards defining the pathogenesis of the hairless phenotype.
AB  - Mutation of the hairless (hr) gene in mice causes severe abnormalities during the
      first hair follicle regression (catagen), resulting in complete baldness. Here,
      we further characterize how hairlessness develops in HRS/J hairless mouse skin
      (hr) by histology, histochemistry, immunohistology, and in situ hybridization. We
      show that, in hr skin, only two defined epithelial cell populations in the distal
      outer root sheath (ORS) retain their integrity, whereas the rest of the ORS
      disintegrates. The surviving distal ORS forms the characteristic utriculi,
      whereas the remnants of the bulge get isolated from other epithelial
      compartments, but retain the capacity to proliferate and to produce either
      columnar epithelial outgrowths or selected dermal cysts. Normal dermal papilla
      structures get lost during the development of hairlessness. Based on the patterns
      of keratin 17 mRNA and neural cell adhesion molecule antigen expression, and on
      the distribution of alkaline phosphatase activity, we propose that dermal cysts
      in hr skin arise from (i) the central ORS, (ii) bulge-derived cells, or (iii) the
      disintegrating proximal ORS under the influence of dermal papilla remnants. The
      hr mutation seems to disrupt the integrity of key functional tissue units in the
      hair follicle, possibly due to a dysregulation of normal, catagen-associated
      apoptosis and/or an impairment of cell adhesion, whereas the distal follicle
      epithelium (including its stem cell region) seems to be largely protected from
      this. Thus, hairless mice offer a unique model for dissecting the as yet obscure
      functional properties of the hr gene product in maintaining follicle integrity
      during normal catagen.

PMID- 9620298
TI  - Organized skin structure is regenerated in vivo from collagen-GAG matrices seeded
      with autologous keratinocytes.
AB  - A well-characterized collagen-glycosaminoglycan matrix (CGM) that has been shown
      to function as a dermal analog was seeded with freshly disaggregated autologous
      keratinocytes and applied to full-thickness wounds in a porcine model. CGM were
      impregnated with 50,000 keratinocytes per cm2, a seeding density that produces a
      confluent epidermis within 19 d post-grafting and affords a 60-fold surface
      expansion of the donor epidermis. In this study, the temporal sequence of events
      in epidermal and neodermal formation was analyzed histopathologically and
      immunohistochemically from 4 to 35 d post-grafting. The epidermis was observed to
      form from clonal growth of individual keratinocytes into epithelial cords and
      islands that gradually enlarged, coalesced, differentiated to form large horn
      cysts, and finally reorganized at the graft surface to form a fully
      differentiated, normally oriented epidermis with rete ridges. Simultaneously, a
      neodermis formed from migration of endothelial cells, fibroblasts, and
      macrophages into the CGM from the underlying wound bed, resulting in formation of
      blood vessels, the production of abundant extracellular matrix, and the
      degradation of the CGM fibers, respectively. Gradually, the stromal cellularity
      of the CGM decreased and collagen deposition and remodeling increased to form a
      neodermal connective tissue matrix beneath the newly formed epidermis. Complete
      dissolution of the CGM occurred, partly as a result of degradation by an ongoing
      foreign-body giant cell reaction that peaked at 8-12 d post-grafting, but neither
      acute inflammation nor evidence of immune stimulation were observed. Within 1 mo,
      many structural components of normal skin were reconstituted.

PMID- 9620299
TI  - Localization of plasminogen activator inhibitor type 2 (PAI-2) in hair and nail:
      implications for terminal differentiation.
AB  - Plasminogen activator inhibitor type 2 (PAI-2) is an unusual serine proteinase
      inhibitor in that it is largely retained within the cell and is found in high
      concentrations in the upper viable layers of human epidermis. Studies using
      transfected cell lines that express high levels of PAI-2 have suggested that this
      inhibitor may confer protection against programmed cell death. To test the
      hypothesis that PAI-2 may protect epithelial cells in vivo from premature
      programmed cell death, we determined expression patterns of PAI-2 in murine hair
      and nail. These epidermal derivatives are comprised of numerous epithelial cell
      types with distinct differentiation pathways. Furthermore, the cyclic nature of
      the follicular epithelium makes it ideal for studying sequential stages of cell
      differentiation and death. PAI-2 mRNA and protein were detected in the
      differentiating cells of the outer root sheath and medulla of the follicle during
      the anagen phase of the hair growth cycle. PAI-2 was also detected in the
      permanent portion of the catagen follicle. In the telogen phase of the hair
      growth cycle, PAI-2 was limited to the postmitotic cells of the outer root sheath
      directly abutting the club hair. In the nail, PAI-2 was detected in the
      differentiating cells of the matrix and nail bed. This consistent, selective
      distribution of PAI-2 in the postmitotic, maturing cells prior to terminal
      keratinization and death suggests that (i) PAI-2 may be considered as a
      differentiation marker for many epithelial cell types, and (ii) PAI-2 is
      appropriately positioned to protect epithelial cells from premature demise.

PMID- 9620300
TI  - Expression of neuropsin in the keratinizing epithelial tissue-immunohistochemical
      analysis of wild-type and nude mice.
AB  - Neuropsin is a trypsin-type serine protease that was first cloned from the mouse
      brain as a factor related to neural plasticity. Subsequent in situ hybridization
      histochemical analysis indicated a broad localization of its mRNA throughout the
      whole body, although the details remain obscure. In this study, we showed that
      neuropsin immunoreactivity is localized in the keratinized stratified epithelia
      of the mouse epidermis, hair, tongue, palate, nasal cavity, pharynges, esophagus,
      and forestomach. In the skin and mucous membranes, neuropsin immunoreactivity was
      found in the stratum spinosum and the stratum granulosum. The immunoreactivity in
      the former sublayer was mainly present in the cytoplasm, but that in the latter
      sublayer was exclusively present in the intercellular space or on the outer
      surface of the cell membrane and thus exhibited a lamellar-like peripheral
      distribution. During development, the appearance of neuropsin immunoreactivity in
      the various epithelia was found at embryonic days 14.5-15.5, prior to formation
      of the stratum corneum. More extensive expression of neuropsin immunoreactivity
      was found in the nude mouse skin and mucous membranes than in wild-type mice.
      Because the nude mouse is characterized by genetic impairment of keratinization,
      such abnormal neuropsin expression might be caused or affected by this
      impairment. Therefore, neuropsin, an extracellular serine protease, is suggested
      to be involved in keratinization in the stratified epithelia.

PMID- 9620301
TI  - Expression of the tumor suppressor gene product p16INK4 in benign and malignant
      melanocytic lesions.
AB  - The gene MTS1 encodes p16INK4, an inhibitor of cyclin-dependent kinase 4, and is
      frequently deleted, mutated, or silenced by promoter methylation in melanoma
      cells and in the germline of familial melanoma patients. Although MTS1 may thus
      be the candidate melanoma suppressor gene that maps to chromosome 9p21, it is not
      clear how dysfunction at that locus temporally relates to melanoma progression.
      To further test its role in sporadic melanoma, the expression of p16INK4-protein
      and -mRNA was characterized in melanomas and melanocytic nevi by
      immunocytochemistry and in situ reverse transcriptase-polymerase chain reaction.
      Histologic tissue sections were immunolabeled with anti-p16INK4 antibody for 108
      melanocytic lesions, including common and atypical nevi, in situ melanomas,
      primary invasive melanomas, and metastatic tumors. A subset of the lesions was
      analyzed for expression of p16INK4-mRNA, employing forward and reverse intron
      bridging primers for reverse transcriptase-polymerase chain reaction
      amplification of the transcript corresponding to exons 1 and 2 of MTS1. Strong
      immunolabeling was detected in the melanocytes of common nevi and of nevi with
      architectural disorder and cytologic atypia. By digital image analysis, in
      contrast, labeling intensity decreased significantly and progressively in the
      melanocytes of in situ, invasive, and metastatic melanomas. Results from the in
      situ reverse transcriptase-polymerase chain reaction analysis were confirmatory,
      showing a strong signal in the melanocytic nevi but progressive signal
      attenuation with increasing stage of melanoma. These data indicate correlation
      between gradual loss of expression of the MTS1 locus and progression of melanoma,
      further supporting an emerging role for the gene in the malignant transformation
      of melanocytes. The failure to demonstrate reduced expression in nevi suggests
      either that these lesions are not an early stage in melanoma development, in
      contrast to prevailing assumptions, or that loss of p16INK4 function is not an
      initiating event in melanocyte transformation.

PMID- 9620302
TI  - Expression of CCAAT/enhancer binding proteins (C/EBP) is associated with squamous
      differentiation in epidermis and isolated primary keratinocytes and is altered in
      skin neoplasms.
AB  - The epidermis is a stratified squamous epithelium composed primarily of
      keratinocytes that undergo sequential changes in gene expression during
      differentiation. CCAAT/enhancer binding proteins (C/EBP) are members of the bZIP
      family of DNA binding proteins/transcription factors. Northern analysis
      demonstrated that C/EBPalpha, C/EBPbeta, and C/EBPdelta mRNA are expressed in
      mouse epidermis and their mRNA levels were generally greater than those observed
      in other tissues known to express high levels of C/EBP. Western analysis of
      isolated epidermal cell nuclei demonstrated the presence of a 42 and 30 kDa
      C/EBPalpha protein and 35 kDa C/EBPbeta protein. Immunohistochemical localization
      of C/EBPalpha and C/EBPbeta in intact interfollicular epidermis revealed that
      C/EBPbeta expression is exclusive to the nuclei of a three-cell cluster of
      suprabasal keratinocytes that is morphologically consistent with the central
      column of the epidermal proliferative unit, and that C/EBPalpha is expressed in
      the nuclei and cytoplasm of suprabasal keratinocytes and weakly expressed in a
      perinuclear manner in some basal keratinocytes. In squamous cell carcinomas the
      expression of C/EBPalpha and C/EBPbeta was greatly diminished as both the
      intensity of nuclear staining and the number of cells expressing C/EBPalpha and
      C/EBPbeta were reduced. In isolated primary mouse keratinocytes, calcium-induced
      differentiation was accompanied by specific temporal changes in the expression of
      C/EBPalpha, C/EBPbeta, and C/EBPdelta mRNA and C/EBPalpha and C/EBPbeta protein.
      These results implicate a role for the C/EBP family in the regulation of genes
      involved in or specifically expressed during the process of squamous
      differentiation in epidermis.

PMID- 9620303
TI  - The prognostic significance of delayed hypersensitivity to dinitrochlorobenzene
      and mechlorethamine hydrochloride in cutaneous T cell lymphoma.
AB  - Recent studies suggest that cells elaborating type 1 cytokines are important
      mediators of anti-tumor cell-mediated immunity in cutaneous T cell lymphoma. Type
      1 cell-mediated immune responsiveness was assessed in 276 patients with cutaneous
      T cell lymphoma (mycosis fungoides and Sezary syndrome) using 2,4
      dinitrochlorobenzene (DNCB) skin testing as part of the initial evaluation. The
      overall rate of sensitization after one and two DNCB challenges was 32% and 67%,
      respectively, which is much decreased compared with the expected rate of more
      than 95% for normal individuals. Moreover, the frequency of DNCB sensitization
      and allergic contact dermatitis to topically applied mechlorethamine decreased
      with advancing stage of disease. In addition to the expected strong correlation
      with stage, we observed that patients who were DNCB test positive were
      significantly less likely to experience disease progression and had a better
      overall prognosis compared with DNCB-negative patients. These results support the
      concept that cell-mediated responses are important in cutaneous T cell lymphoma,
      and that augmentation of these responses would be therapeutically beneficial.

PMID- 9620304
TI  - The relationship between hyperproliferation and epidermal thickening in a mouse
      model for BCIE.
AB  - Epidermal thickening is a phenomenon common to many genodermatoses but little is
      known about the underlying causes. We have recently created a mouse model for the
      human skin disease bullous congenital ichthyosiform erythroderma by gene
      targeting. Mice heterozygous for a truncated keratin 10 gene exhibit acanthosis
      and hyperkeratosis as seen in the human disease. The degree of epidermal
      thickening is highly variable, offering a novel opportunity to investigate how
      epidermal homeostasis is modulated in keratin disorders by comparing epidermis
      from different body regions. We have performed bromodeoxyuridine labeling
      experiments and detected proliferation antigens by immunohistochemical means to
      compare proliferation in the epidermis of wild-type and heterozygous mice. These
      results have been compared with the expression of epidermal differentiation
      markers and of the "hyperproliferation associated" keratins K6 and K16. These
      experiments indicated that hyperproliferation is only partly responsible for the
      morphologic changes and that other mechanisms such as decreased desquamation are
      likely to be involved.

PMID- 9620305
TI  - Genetics of psoriasis: paternal inheritance and a locus on chromosome 6p.
AB  - The pathogenesis of psoriasis is not fully understood, but population and twin
      studies suggest a large heritable component to the etiology. Several large
      population studies have also suggested a parental sex effect. Since 1994, three
      main genetic loci (on chromosomes 17q, 4q, and 6p) have been reported in genome
      scans. With a view to elucidating the genetic basis of psoriasis, we have carried
      out linkage analysis in a large number of families with well-characterized
      psoriasis. From a cohort of 1250 probands with psoriasis, 395 individuals (301
      affected, 94 unaffected) in 103 families were recruited. Each subject was
      carefully examined by an experienced dermatologist and stringent diagnostic
      criteria applied. Genotypes were generated at 11 polymorphic loci on chromosomes
      17q, 4q, and 6p and the results were analyzed parametrically and
      nonparametrically. In the population from which the probands were drawn, there
      was evidence of a parental sex effect, more probands having an affected father
      than an affected mother. Genetic anticipation was also apparent and most marked
      if the disease was inherited from the father. The loci on chromosomes 17 and 4
      were not replicated but there was strong evidence for linkage to chromosome 6p
      (maximum two point LOD score 4.63 at D6S291). The evidence for linkage in sibling
      pair analysis was greatest when the allele was of paternal origin and was most
      significant in those families without psoriatic arthritis. These studies confirm
      the presence of a susceptibility gene on chromosome 6p. The available evidence
      suggests that a different genetic susceptibility may underlie psoriasis and
      psoriatic arthritis.

PMID- 9620306
TI  - Requirement of the IL-2 receptor beta chain for the development of Vgamma3
      dendritic epidermal T cells.
AB  - Vgamma3 TCR cells develop in the fetal thymus and migrate to the skin as
      dendritic epidermal T cells (DETC). Fetal Vgamma3 thymocytes differentiate from
      immature heat stable antigen (HSA)high cells to mature HSAlow cells and the
      latter subset predominantly expresses IL-2 receptor beta chain (IL-2Rbeta). In
      this study, the role of IL-2Rbeta in the development of Vgamma3 cells was
      determined in IL-2Rbeta-deficient mice. There was a moderate reduction of mature
      HSAlow Vgamma3 thymocytes in IL-2Rbeta-deficient mice. Small numbers of Vgamma3
      DETC were detected in the fetal skin of IL-2Rbeta-deficient mice, but they were
      absent in newborn and adult mice. These results suggest that IL-2Rbeta may
      transduce the crucial signal for survival and/or expansion of Vgama3 cells in the
      fetal thymus and in the fetal skin. In normal mice, IL-15 but not IL-2 mRNA was
      expressed in the fetal epidermis and exogenous addition of low concentration of
      IL-15 to fetal skin organ culture induced proliferation of Vgamma3 DETC. The
      dependence of fetal Vgamma3 DETC on the expression of IL-2Rbeta and the presence
      of IL-15 mRNA in the fetal epidermis imply an essential role of IL-15 signaling
      through IL-2Rbeta in the selective localization of this gammadelta T cell
      subpopulation in the skin.

PMID- 9620308
TI  - Regulatory effects of heat on normal human melanocyte growth and melanogenesis:
      comparative study with UVB.
AB  - Although energy-rich ultraviolet B (UVB) is considered to be primarily
      responsible for most of the effects associated with solar radiation, small energy
      recorded as heat appears to contribute to the biologic effects of solar radiation
      on the skin. We compared the effects of heat and UVB on normal human melanocyte
      functions. In monolayer culture the following was found. (i) Heat-treated
      melanocytes showed an increased dendricity and exhibited a larger cell body
      compared with nontreated melanocytes. (ii) After multiple treatments with UVB (20
      mJ per cm2, 312 nm) or heat (42 degrees C for 1 h) for 3 d, melanocytes had a
      lower survival than nontreated melanocytes, but they resumed proliferation within
      6 d in the same manner as seen in control. (iii) The expression levels of cell
      cycle regulators, p53 and p21 proteins, were increased after multiple treatments
      with UVB or heat. (iv) The tyrosinase (dopa-oxidase) activity per cell was
      increased after the multiple treatments with UVB or heat. (v) The number of dopa
      positive melanocytes in coculture with keratinocytes in epithelial sheets was
      greatly increased by UVB or heat treatments. (vi) Similarly, the increased number
      of tyrosinase-related protein 1 positive melanocytes was seen in skin equivalents
      after UVB (100 mJ per cm2) or heat (42 degrees C for 1 h) treatments for 7 d.
      These results suggest that heat shares significant biologic activities with UVB
      in melanocyte functions. These results could be considered as one of the
      protective or adaptive responses of the skin pigmentary system to the
      environment.

PMID- 9620307
TI  - H2O2 is an important mediator of UVB-induced EGF-receptor phosphorylation in
      cultured keratinocytes.
AB  - Exposure of human keratinocytes to physiologic doses of ultraviolet B (UVB)
      radiation induces phosphorylation of the epidermal growth factor receptor (EGFR).
      We demonstrate that H2O2 generated by UVB mediates EGFR phosphorylation. Using
      dihydrorhodamine 123 as a specific fluorescent dye probe, we show that UVB
      irradiation (50-800 J per m2) of keratinocytes leads within minutes to
      concentration-dependent intracellular production of H2O2. A corresponding
      concentration-dependent increase in the release of extracellular H2O2 was
      measured by using Amplex, a derivative of dihydrophenoxazine. The levels of
      intracellular H2O2 that are induced by UVB irradiation and that stimulate EGFR
      phosphorylation correlate strongly with the response induced by exogenously added
      H2O2. UVB or H2O2 demonstrated concentration- and time-dependent stimulation of
      EGFR phosphorylation that was initially observed within 1-5 min and exhibited a
      proportionate delay for UVB-induced production of H2O2. EGFR phosphorylation
      induced by UVB or H2O2 declined significantly toward baseline levels by 4 h and
      could be restimulated after H2O2 but not after UVB exposure. Phosphorylation of
      EGFR was inhibited by the structurally unrelated antioxidants butylated
      hydroxyanisole, N-acetyl-L-cysteine, and pyrrolidine dithiocarbamate, or by the
      H2O2-degrading enzyme catalase. These data indicate that generation of H2O2 by
      UVB radiation of human keratinocytes participates in the rapid, ligand
      independent phosphorylation of EGFR and implicate H2O2 as a biologic mediator in
      EGFR activation and regulation of the downstream signaling cascade. UVB-induced
      H2O2 has the potential to initiate or modulate early EGFR-mediated signaling
      events that could play an important role in the cellular response to oxidative
      stress.

PMID- 9620309
TI  - UVB radiation preferentially induces recruitment of memory CD4+ T cells in normal
      human skin: long-term effect after a single exposure.
AB  - Acute, low-doses of ultraviolet (UV)-B radiation affect the immune competent
      cells of the skin immune system. In this study, we examined the time-dependent
      changes of the cutaneous T cell population in normal human volunteers following a
      single local exposure to UV. Solar-simulated UV radiation caused an initial
      decrease in intraepidermal T cell numbers, even leading to T cell depletion at
      day 4, whereupon a considerable infiltration of T cells in the epidermis occurred
      that peaked at day 14. In the dermis the number of T cells was markedly increased
      at days 2 (peak) and 4 after irradiation, and subsequently declined to the
      nonirradiated control values at day 10. Double-staining with several T cell
      markers showed that the T cells, infiltrating the (epi)dermis upon UV exposure,
      were almost exclusively CD4+ CD45RO+ T cells, expressing an alpha/beta type T
      cell receptor, but lacking the activation markers HLA-DR, VLA-1, and IL-2R.
      Application of UVB radiation resulted in similar dynamics of T cells, indicating
      that the UVB wavelengths within the solar-simulated UV radiation were responsible
      for the selective influx of CD4+ T cells. In conjunction with UVB-induced
      alterations in the type and function of antigen-presenting cells (i.e.,
      Langerhans cells and macrophages), the changes of the cutaneous T cell population
      may also contribute to UVB-induced immunosuppression at skin level in man.

PMID- 9620310
TI  - Hemodynamics in nailfold capillaries of patients with systemic scleroderma:
      synchronous measurements of capillary blood pressure and red blood cell velocity.
AB  - There is increasing evidence that endothelial damage occurs at a very early stage
      during the course of systemic scleroderma. Endothelial damage is accompanied by
      impaired microvascular function, which has clearly failed in patients with
      systemic scleroderma, as evidenced by necrosis of the fingertips in severe cases.
      We investigated two important determinants of microvascular function, namely
      capillary blood pressure and capillary red blood cell velocity, simultaneously in
      the same capillary. In patients with systemic scleroderma and in healthy
      volunteers matched for age and sex, capillary blood pressure was measured by
      direct cannulation and capillary red blood cell velocity by video microscopy.
      Capillary blood pressure and capillary red blood cell velocity were significantly
      lower in patients (14.27 +/- 4.34 mmHg, 230 +/- 310 microm per s) than in healthy
      controls (19.06 +/- 3.69 mmHg, p < 0.008, and 910 +/- 240 microm per s, p <
      0.003) at an ambient temperature of 22 degrees C, whereas no significant
      difference in skin temperature was observed (23.7 +/- 0.9 degrees C vs 24.7 +/-
      1.9 degrees C) and no occlusion of finger arteries was detected. Capillary blood
      pressure in enlarged capillaries did not differ from that in normal-shaped
      capillaries in the patients (correlation of diameter and capillary blood
      pressure, R2 = 0.04), which was also the case with capillary red blood cell
      velocity (R2 = 0.13). Capillary pulse pressure amplitude and capillary red blood
      cell velocity showed a strong correlation (R2 = 0.81), suggesting that the
      pressure gradient across the capillary loop, which is the driving force for
      capillary red blood cell velocity, was mainly dependent on precapillary
      resistance. These observations reflect the inadequate microvascular function in
      systemic scleroderma, which may be due mainly to a pathophysiologic functional
      increase in precapillary resistance, even at comfortable ambient temperatures.

PMID- 9620311
TI  - Murine cytomegalovirus is not associated with alopecia areata in C3H/HeJ mice.

PMID- 9620312
TI  - Antigen receptor beta chain variable region usage by CD4+ and CD8+ T cells in
      psoriasis.

PMID- 9620313
TI  - Investigation of water sorption on porcine stratum corneum by very small angle
      neutron scattering.

PMID- 9620314
TI  - Hepatic steatosis: innocent bystander or guilty party?

PMID- 9620315
TI  - Immunoreactivity of porcine heart dihydrolipoamide acetyl- and succinyl
      transferases (PDC-E2, OGDC-E2) with primary biliary cirrhosis sera:
      characterization of the autoantigenic region and effects of enzymatic
      delipoylation and relipoylation.
AB  - Analysis of the primary structure of the lipoyl domain of the dihydrolipoamide
      acetyltransferase (PDC-E2) component of the porcine pyruvate dehydrogenase
      complex (PDC) reveals a high degree of homology with M2 antigen and human PDC-E2.
      The porcine PDC-E2 and the dihydrolipoamide succinyltransferase (OGDC-E2)
      component of the porcine 2-oxoglutarate dehydrogenase complex (OGDC) were
      identified as mitochondrial autoantigen with sera from patients with primary
      biliary cirrhosis (PBC). Immunodominant regions (autoepitopes) on the porcine-PDC
      E2 component have been mapped to two regions around Lys-46 (outer lipoyl domain)
      and Lys-173 (inner lipoyl domain), which contained covalently bound lipoic acid
      prosthetic group. When these lipoyl domains were cleaved at Asp-45 or Asp-172
      with endoproteinase Asp-N, the autoantigenicities of the two domains completely
      disappeared; this suggested the requirement of Asp-45 or Asp-172 residues for the
      immunoreaction with PBC sera. In addition, a single 14-amino acid epitope peptide
      histidine-substituted at Asp-172 did not exhibit competitive inhibition of
      autoantigen binding. Fragmentation of lipoyl domain of the porcine PDC-E2 by
      limited proteolysis and BrCN-cleavage after alkylation resulted in rapid loss of
      autoantigenicity. Enzymatic delipoylation and relipoylation of the complexed and
      free PDC-E2 and OGDC-E2 components did not influence immunoreactivity with PBC
      sera.

PMID- 9620316
TI  - Detection of reovirus RNA in hepatobiliary tissues from patients with
      extrahepatic biliary atresia and choledochal cysts.
AB  - Extrahepatic biliary atresia (EHBA) and choledochal cysts (CDC) are important
      causes of obstructive jaundice in pediatric patients. Viruses in general, and
      reoviruses in particular, have long been considered as possible etiologic agents
      responsible for inciting the inflammatory process that leads to these infantile
      obstructive cholangiopathies. In an effort to determine whether reovirus
      infection is associated with these disorders, we used a sensitive and specific
      reverse-transcriptase polymerase chain reaction (RT-PCR) technique designed to
      amplify a portion of the reovirus L1 gene segment from extracts of liver and/or
      biliary tissues. These tissues were obtained at the time of liver biopsy or
      surgical procedures from 23 patients with EHBA, 9 patients with CDC, and 33
      patients with other hepatobiliary diseases. Hepatic and biliary tissues obtained
      at autopsy from 17 patients who died without known liver or biliary disease were
      also analyzed. Reovirus RNA was detected in hepatic and/or biliary tissues from
      55% of patients with EHBA and 78% of patients with CDC. Reovirus RNA was found
      also in extracts of hepatic and/or biliary tissue from 21% of patients with other
      hepatobiliary diseases and in 12% of autopsy cases. The prevalence of reovirus
      RNA in tissues from patients with EHBA and CDC was significantly greater than
      that in patients with other hepatobiliary diseases (chi2 P = .012 EHBA vs. OTHER,
      P = .001 CDC vs. OTHER), or AUTOPSY cases (chi2 P = .006 EHBA vs. AUTOPSY, P <
      .001 CDC vs. AUTOPSY).

PMID- 9620317
TI  - Immunohistochemical demonstration of beta-naphthoflavone-inducible cytochrome
      P450 1A1/1A2 in rat intrahepatic biliary epithelial cells.
AB  - Although intrahepatic biliary epithelial cells are targets for certain
      hepatotoxic chemicals, including some procarcinogens, their ability to
      monooxygenate, and thereby bioactivate and inactivate xenobiotics, remains to be
      established. Thus, the present study was undertaken to immunohistochemically
      determine if cytochrome P450 (CYP) 1A1/1A2 is present and can be induced within
      these nonparenchymal liver cells. Immunoperoxidase and immunofluorescent staining
      for CYP1A1/1A2 was detected within intrahepatic biliary epithelial cells as well
      as hepatocytes of control rats and was markedly enhanced in both cell types by
      beta-naphthoflavone (BNF). Color confocal laser microscopic analyses of dual
      immunofluorescent staining for CYP1A1/1A2 and cytokeratins 6 and 9 (56 and 64 kd,
      respectively) provided unequivocal evidence for the presence and induction of
      CYP1A1/1A2 within intrahepatic bile duct epithelia. Moreover, microdensitometric
      analyses of immunoperoxidase staining intensities for CYP1A1/1A2 revealed that
      intrahepatic biliary epithelial cells of control rats contain 44%, 56%, and 58%
      as much CYP1A1/1A2 as do centrilobular, midzonal, and periportal hepatocytes,
      respectively. These analyses further revealed that BNF increased the content of
      CYP1A1/1A2 in biliary epithelial cells by approximately 120%, while CYP1A1/1A2
      levels in centrilobular, midzonal, and periportal hepatocytes were increased by
      82%, 159%, and 160%, respectively. The results of this study represent the first
      in situ demonstration that mammalian intrahepatic biliary epithelial cells
      contain a CYP isoform, and further that CYP1A1/1A2 can be induced in these cells
      by BNF. These findings therefore indicate that intrahepatic biliary epithelial
      cells can oxidatively metabolize xenobiotics in situ and that their ability to
      bioactivate and inactivate xenobiotics can be significantly enhanced by
      CYP1A1/1A2 induction.

PMID- 9620318
TI  - Diet and gallstones in Italy: the cross-sectional MICOL results.
AB  - Fifteen thousand nine hundred ten men and 13,674 women (age, 30-69 years) were
      enrolled in an epidemiological survey of the general population, between December
      1984 and April 1987. Each participant was submitted to ultrasonography (US) of
      the gallbladder and completed a food-frequency questionnaire, covering 38 food
      items. A common portion size was identified and subjects were asked how often
      each item was consumed. Nutrient intake was computed by multiplying the intake
      frequency and nutrient content per portion for each item, and then by summing the
      product over all foods. Each nutrient intake was adjusted for energy intake.
      Alcohol intake was calculated by summing the consumption of wine, beer, and
      liquor. Having excluded subjects aware of having gallstones (GS) or previously
      submitted to cholecystectomy (to avoid prothopatic bias), 787 males and 1,014
      females with GS and 14,272 males and 10,836 females without GS were available for
      analysis. Relative risks (RR) of GS were computed by quintiles of nutrient
      intake. The overnight fasting period was calculated as the difference between the
      specified time of dinner and the time of the next meal (breakfast or lunch). A
      significant negative association was found between RR of GS and total energy
      intake for males (chi2 for trend = 8.37; P = .004), fiber intake for females
      (chi2 = 5.45; P = .02), and daily alcohol consumption for males (chi2 = 10.86; P
      = .001). A positive association was observed between RR of GS and carbohydrate
      (chi2 = 5.95; P = .01 for males; chi2 = 9.39; P = .002 for females) and protein
      intake only for males (chi2 = 10.92; P = .01). Prevalence of GS was higher among
      subjects who had an overnight fasting period of over 12 hours than subjects with
      that of less than 12 hours. (RR: 1.35; 95% CI: 1.01-1.80 for males; RR: 1.28; 95%
      CI: 1.03-1.60 for females). These data do not confirm that high energy intake is
      associated with an increased risk of GS. Factors protecting against GS comprise:
      low carbohydrate (males and females) and protein (males) intakes, high fiber
      (females) and moderate alcohol intake (males) consumption, and a shorter
      overnight fasting period for both sexes.

PMID- 9620319
TI  - aly/aly mice: a unique model of biliary disease.
AB  - An autosomal recessive murine mutation, coined "aly/aly" or "alymphoplasia," was
      recently reported. Homozygotes for aly are defective in both humoral and cell
      mediated immune function and have diffuse lymphoid cell infiltration of various
      tissues, particularly around the conduit ducts of the pancreas and salivary
      glands. In pilot studies in our laboratories, aly/aly mice were found to have
      peculiar biliary tract lesions, which were analyzed histologically and
      immunohistochemically in the present study. The livers of aly/aly mice older than
      8 weeks consistently showed a variable lymphoid cell infiltration with lymph
      follicle formation in portal tracts; intrahepatic biliary epithelial cells showed
      various types of damage including pseudopyloric gland metaplasia and
      proliferative changes. In addition, the extrahepatic bile duct and intrahepatic
      large bile duct were found to contain an acidophilic substance in their
      epithelial cytoplasm. In the lumen and occasionally in the cytoplasm of these
      bile ducts, acidophilic crystals were also seen. Ultrastructurally, the
      intracytoplasmic acidophilic substances consisted of membrane-bound
      intracytoplasmic inclusions with homogeneous electron density, likely derived
      from rough endoplasmic reticulum (ER). Immunohistochemically, the cytoplasmic
      acidophilic substances were simultaneously positive for cystatin C, gastrin,
      serotonin, and somatostatin. In contrast, the acidophilic crystals did not react
      with any of these antibodies. These findings suggest that the intracytoplasmic
      acidophilic substances may contain a precursor of the peptide hormones, possibly
      because of defective secretion or intracellular transport. We believe that the
      aly/aly mouse is a useful model for the analysis of biliary metabolic events, and
      for studies of the interaction of the immune system and biliary destruction.

PMID- 9620320
TI  - Cholesterol crystallization in human gallbladder bile: relation to gallstone
      number, bile composition, and apolipoprotein E4 isoform.
AB  - Patients with multiple cholesterol gallstones are at increased risk of recurrence
      after nonsurgical therapy, possibly because of fast biliary cholesterol
      crystallization. Serum apolipoprotein E4 (apo E4) is a risk factor for primary
      cholesterol gallstone formation as well as recurrence. We examined potential
      effects of stone number and apolipoprotein E genotype on crystallization and on
      various crystallization-influencing factors in gallbladder biles of 36
      cholesterol stone patients (25 multiple stones: 10 carrying the epsilon4 allele).
      Biliary cholesterol saturation, bile salt composition or concentrations of total
      protein, immunoglobulin (Ig)A, IgG, alpha1-acid glycoprotein, haptoglobin, or
      mucin--all crystallization promoters--did not differ between multiple and
      solitary stone patients, apparently not explaining different speed of
      crystallization (crystal observation time 3.5 +/- 0.6 days vs. 12.7 +/- 2.4 days,
      respectively; P = .0003). In contrast, biliary aminopeptidase-N activities (2,607
      +/- 592 mU/mL vs. 947 +/- 185 mU/mL; P = .04) were higher and IgM levels (179 +/-
      39 vs. 65 +/- 8 mg/L; P = .09) tended to be higher in the case of multiple
      stones. Although patients carrying the epsilon4 allele had similar stone numbers
      and crystallization as patients without the epsilon4 allele, their cholesterol
      saturation index (CSI) was lower (1.08 +/- 0.09 vs. 1.54 +/- 0.13; P = .01),
      whereas total protein and bile salt concentrations tended to be higher with
      preferential taurine-conjugation. In conclusion, fast cholesterol crystallization
      is associated with multiple stones but not with apolipoprotein E4. Whereas fast
      crystallization may contribute to high recurrence rates after nonsurgical therapy
      in case of multiple gallstones, the mechanism for increased risk of gallstone
      formation in patients carrying the epsilon4 allele remains unknown.

PMID- 9620321
TI  - Visual attention in cirrhotic patients: a study on covert visual attention
      orienting.
AB  - Attentional dysfunction, which influences overall cognitive productivity, is not
      well characterized in cirrhotic patients. The aim of this study was to clarify
      the features of covert visual attention orienting in cirrhotics without overt
      hepatic encephalopathy. One hundred consecutive cirrhotic patients and 40
      controls were enrolled. Visual covert attention orienting was assessed by the
      Posner test, which evaluates the effect of a cue on visual reaction times.
      Patients were characterized by the number connection test (NCT) and
      electroencephalographic (EEG) spectral analysis. The severity of liver disease
      was graded using standard laboratory parameters and the Child-Pugh's
      classification. Fifty-five psychometric and EEG evaluations were performed in the
      follow-up of 17 patients to assess the relationship between the variations of
      psychometric and neurophysiological findings. NCT and quantified-EEG parameters
      (altered in 19% and 40% of cirrhotic patients, respectively) were linked to each
      other and to the severity of liver disease. The Posner test showed a delay of
      visual reaction times in class B-C cirrhotic patients. Reaction times were
      correlated with ammonia and EEG parameters. The effect of the cue was higher in
      cirrhotic patients than in controls, particularly in the invalid position. This
      study suggests that cirrhotic patients have a reduced activity rate and reduced
      capacity to disengage attention previously focused on a cue. Such alterations are
      linked to NCT and EEG findings.

PMID- 9620322
TI  - Early cyclosporine monotherapy in liver transplantation: a 5-year follow-up of a
      prospective, randomized trial.
AB  - Maintenance of adequate immunosuppression and avoidance of side-effects are the
      goals of long-term management of all organ-transplanted patients. We here report
      the final results of a prospective, randomized trial comparing early cyclosporine
      monotherapy versus double-drug therapy (cyclosporine and steroids) in adult liver
      transplantation patients. One hundred four patients were randomized 3 months
      after transplantation either to continue (Group I = 50 patients) or to stop
      steroids (Group II = 54 patients). Patients on a double-drug regimen were
      maintained long term on methylprednisolone at a dose of 0.1 mg/kg/d. Target
      cyclosporine trough levels were between 150 and 250 ng/mL in both groups. Our
      main points of interest were the prevalence of acute and chronic rejections and
      steroid-related side-effects in the two groups of patients. Mean follow-up was 41
      +/- 16 months (range, 4-68 months). Patient actuarial survival 2 and 5 years
      after randomization was similar in the two groups (82% vs. 83% and 82% vs. 77%).
      The prevalence of acute rejections after randomization was, respectively, 8% and
      4%. A single episode of chronic rejection was observed only in a patient on long
      term steroid therapy. Side-effects of steroid therapy were less frequent in
      patients weaned off steroids, and when considering hypertension and diabetes, the
      differences between the two groups were statistically significant. Early
      cyclosporine monotherapy is a safe undertaking in liver transplantation because
      it allows a significant reduction of steroid-related side-effects without
      increasing the risk of acute and chronic rejection. After 5 years, patient
      survival was similar in patients with or without steroids.

PMID- 9620323
TI  - Potassium channels participate in gastric mucosal protection in rats with partial
      portal vein ligation.
AB  - Glybenclamide, an adenosine triphosphate-dependent potassium (K+(ATP)) channel
      blocker, lowered portal pressure and attenuated the hyperdynamic splanchnic
      circulation in rats with partial portal vein ligation (PPVL). The purpose of this
      report was to confirm these observations and to test the hypothesis that
      glybenclamide could reduce acidified ethanol-induced gastric mucosal injury in
      rats with PPVL. Gastric mucosal blood flow (hydrogen gas clearance), systemic
      blood pressure, and portal pressure were monitored in rats with PPVL or sham
      operation (SO). Intravenous glybenclamide (20 mg/kg) or vehicle was administered,
      followed by intragastric acidified ethanol (0.15 N HCl and 15% ethanol). The area
      of gastric mucosal lesions was assessed by image analysis. In contrast to
      published findings, there was no significant elevation of portal pressure after
      glybenclamide administration in rats with PPVL. Glybenclamide did not alter the
      gastric mucosal hyperemia in these rats. Glybenclamide significantly increased
      mucosal injury. The data are consistent with the hypothesis that K+(ATP) channels
      play a role in protecting the gastric mucosa in rats with PPVL.

PMID- 9620324
TI  - Suppression of murine experimental autoimmune hepatitis by T-cell vaccination or
      immunosuppression.
AB  - Patients with autoimmune hepatitis (AIH) usually require immunosuppressive
      therapy for many years, if not for a lifetime. Experimental immunotherapy such as
      T-cell vaccination aims at manipulating the immune system in such a way that
      autoimmunity is specifically regulated to enable long-lasting correction of the
      disease process. We aimed to test the feasibility of T-cell vaccination as well
      as conventional immunosuppression in the murine model of experimental autoimmune
      hepatitis (EAH). EAH was induced in 5- to 7-week-old BALB/c mice by immunization
      with syngeneic liver homogenate in complete Freund's adjuvant. For T-cell
      vaccination, splenocytes were removed from animals 14 days after induction of EAH
      and from control animals, and activated in vitro by mitogen stimulation with
      Concanavalin A (Con A). Activated T cells were irradiated and injected at 5 x
      10(7) cells per animal as T-cell vaccine. Immunosuppression in control animals
      was performed with prednisolone with or without azathioprine. T-cell vaccination
      with T cells from EAH animals, but not with irrelevant T cells, was able to
      protect animals from EAH, reducing the average disease severity from 2.2 (+/-0.3)
      to 0.5 (+/-0.3) (P < .01). T-cell vaccination was also able to treat EAH, because
      application of the vaccine 2 weeks after induction of the disease significantly
      reduced disease activity at week 4 from 2.4 (+/-0.4) to 1.1 (+/-0.2) (P < .05).
      Both passive transfer of disease and the capacity to protect by T-cell
      vaccination was mediated by CD4 T cells. Specific cellular recognition of
      activated disease-inducing T cells could be detected in vaccinated animals.
      Immunosuppressive drugs could also suppress EAH. Thus, T-cell vaccination in EAH
      is feasible and effective. Stimulation of a regulatory T-cell network is the
      likely mechanism of action by which T-cell vaccination can suppress EAH.

PMID- 9620325
TI  - An intravital fluorescence microscopic study of hepatic microvascular and
      cellular derangements in developing cirrhosis in rats.
AB  - Quantitative data defining the relationship between the hepatic microcirculation
      and the development of liver pathological changes could provide a basis for a
      better understanding of fibrogenic processes, such as cirrhosis. Therefore, we
      established the technique of intravital fluorescence microscopy and computer
      assisted microcirculation analysis systems in developing cirrhosis in rats with
      the aim of quantitatively assessing the association of hepatic microvascular
      morphology with its disordered acinar architecture, and nonparenchymal cell
      transformation with collagen deposition, parenchymal cell loss, and liver
      dysfunction. In animals chronically exposed to carbon tetrachloride (CCl4), the
      most significant microvascular changes progressively observed in vivo were the
      concomitant appearance of 1) sinusoid-free space around dilated postsinusoidal
      venules with 2) substituting occurrence of yellow-green autofluorescent collagen
      deposition, 3) reduction in sinusoidal density, but 4) increase of vascular lumen
      caused by the formation of shunting vessels bypassing the sinusoids. Present on
      line analysis further indicated the local coincidence of changed spatial
      distribution of Ito cells (accumulation of vitamin A ultraviolet autofluorescence
      in zone 3) with fibrotic autofluorescent septa, causing significant collapse of
      parenchymal tissue (hepatocellular bis-benzamide fluorescence) and diminution of
      hepatocellular excretory function (bile flow). Regression analysis revealed
      strong correlations between loss of parenchymal tissue and both collagen
      deposition and sinusoidal rarefication, as well as between sinusoidal
      rarefication and collagen deposition. Thus, sequential in vivo analysis presented
      herein provides the new information on the concomitant onset of cellular,
      fibrotic, and microvascular changes in developing fibrosis/cirrhosis, excluding
      that distinct cellular or fibrotic alterations are a prerequisite for the
      manifestation of microcirculatory and vascular derangements or vice versa.

PMID- 9620326
TI  - Clinical significance of microvessel density and vascular endothelial growth
      factor expression in hepatocellular carcinoma and surrounding liver: possible
      involvement of vascular endothelial growth factor in the angiogenesis of
      cirrhotic liver.
AB  - As in other tumors, the assessment of microvessel density (MVD) in hepatocellular
      carcinoma (HCC) may be essential to perform an effective anti-angiogenic therapy
      for this tumor. The relationship between vascular endothelial growth factor
      (VEGF) and MVD of HCC as well as the surrounding liver remains to be elucidated.
      In 71 patients who had undergone curative hepatic resection for HCC, MVD and VEGF
      expressions were evaluated for HCC and the liver by quantitative reverse
      transcription polymerase chain reaction (RT-PCR) and/or immunostaining. The
      intensity and extent of VEGF immunoreactivity were evaluated using a computer
      image analyzer-cell analysis system (CAS). Angiographic data were re-evaluated
      and compared with MVD in 50 tumors. Tumoral MVD was significantly correlated with
      tumor capsule formation (t test, P = .0016). Small HCCs (< or = 2 cm) had a
      significantly lower MVD compared with moderate-sized HCCs (2-5 cm) (t test, P =
      .016), and the MVD of large HCCs was relatively lower than that of moderate
      tumors. Tumor vascularity on angiography was not correlated with the MVD. Neither
      VEGF mRNA levels nor protein expression in HCC were correlated with the tumoral
      MVD or any histopathological features of the tumor. However, cirrhotic livers had
      significantly higher MVD and VEGF expressions compared with noncirrhotic livers
      (t test, P = .0015 and P = .047, respectively). Only the MVD of tumor was
      significantly correlated with intrahepatic recurrence (t test, P = .0048) and
      disease-free survival (DFS) rates (log rank test, P = .0035). Moreover, the MVD
      was an independent predictor for DFS by multivariate analysis (chi2 test, P =
      .03). In conclusion, the MVD in HCC may be involved in the dismal prognosis of
      this tumor, and VEGF may be associated with the angiogenic process of the
      cirrhotic liver, but not with the angiogenesis of HCC.

PMID- 9620327
TI  - Dietary iron overload as a risk factor for hepatocellular carcinoma in Black
      Africans.
AB  - Although the iron-loading disease, hereditary hemochromatosis, has a strong
      causal association with hepatocellular carcinoma (HCC), the carcinogenic
      potential of dietary iron overload in Black Africans is not known. We
      investigated this potential by evaluating iron status, alcohol consumption,
      markers for hepatitis B (HBV) and C virus (HCV) infections, and exposure to
      dietary aflatoxin B1 in 24 rural patients with this tumor, 48 race-, sex-, and
      age-matched hospital-based controls, and 75 related or unrelated close family
      members of the cancer patients. Iron overload was defined as a raised serum
      ferritin concentration in combination with a transferrin saturation > or = 60%,
      and was confirmed histologically when possible. Among 24 patients and 48 hospital
      controls, the risk of developing HCC in the iron-loaded subjects was 10.6 (95%
      confidence limits of 1.5 and 76.8) relative to individuals with normal iron
      status, after adjusting for alcohol consumption, chronic HBV and HBC infections,
      and exposure to aflatoxin B1. The risk of HCC in subjects with HBV infection was
      33.2 (7.2, 153.4) (odds ratio [95% confidence limits]), HCV infection 6.4 (0.3,
      133.5), and alcohol consumption 2.0 (0.5, 8.2). Aflatoxin B1 exposure did not
      appear to increase the risk of HCC. The population attributable risk of iron
      overload in the development of HCC was estimated to be 29%. Among 20 cancer
      patients and 75 family members, the risk of developing HCC with iron overload was
      4.1 (0.5, 32.2). We conclude that dietary iron overload may contribute to the
      development of HCC in Black Africans.

PMID- 9620328
TI  - Prognosis of hepatocellular carcinoma with diabetes mellitus after hepatic
      resection.
AB  - We evaluated the effect of diabetes mellitus on the prognosis of hepatocellular
      carcinoma after an elective hepatic resection. Of the 342 patients who underwent
      a hepatic resection between April 1985 and March 1995, 87 (25.4%) were diabetic.
      Postoperative morbidity was more common among diabetics than among nondiabetics
      (36.0% vs. 22.5%, P = .0239). The postoperative survival rate and the cancer-free
      survival rate were also better in patients without diabetes than in those with
      diabetes (P = .0333, P = .0149). The results of a multivariate analysis show
      diabetes mellitus to be an independent and prognostic indicator after a hepatic
      resection with hepatocellular carcinoma. According to the above findings,
      diabetes mellitus is thus considered to be a risk factor for prognosis after
      hepatic resection in patients with hepatocellular carcinoma.

PMID- 9620329
TI  - Liver transplantation for small hepatocellular carcinoma: the tumor-node
      metastasis classification does not have prognostic power.
AB  - Tumoral recurrence rate and survival of patients with hepatocellular carcinoma
      (HCC) treated by orthotopic liver transplantation (OLT) depend on tumor stage.
      Thereby, from the beginning of our program, we selected only patients with
      solitary tumors < or = 5 cm without vascular invasion, thus avoiding the use of
      the tumor-node-metastasis (TNM) staging system as a selection tool. The present
      study reports the results obtained in 58 consecutive patients (52 +/- 8 years, 47
      males) with HCC (7 incidentals) transplanted between 1989 and 1995.
      Transplantation was indicated because of tumor diagnosis in 40 cases and advanced
      liver failure in 18. Mean tumor size at staging was 28.2 +/- 12.1 mm. No adjuvant
      treatment was applied during the waiting period (58.9 +/- 45.1 days). The
      pathological tumor-node-metastasis (pTNM) classification allocated 15 patients to
      stage I, 19 to stage II, 11 to stage IIIA, and 13 to stage IVA showing
      preoperative understaging in 43% of the cases with known tumor. After a median
      follow up of 31 months, only two patients have shown tumor recurrence and fifteen
      have died, the 1-, 3-, and 5-year survival being 84%, 74%, and 74%. All HCV+
      patients remain infected and 94% showed significant liver disease (6 cirrhosis).
      Six patients have had a second transplant. In conclusion, the application of
      restrictive criteria not following the TNM staging system prompts excellent
      results for liver transplantation in patients with HCC, both in terms of survival
      and disease recurrence, even without applying adjuvant treatment; however, the
      survival data should be tempered by the appearance of complications that may
      worsen the long-term prognosis.

PMID- 9620330
TI  - Transarterial embolization versus symptomatic treatment in patients with advanced
      hepatocellular carcinoma: results of a randomized, controlled trial in a single
      institution.
AB  - This randomized, controlled trial assessed the effect of transarterial
      embolization (TAE) (without associated chemotherapy) on the survival of patients
      with nonsurgical hepatocellular carcinoma (HCC). Eighty consecutive patients were
      randomized to treatment with embolization (Group A, n = 40), or to symptomatic
      treatment (Group B, n = 40), there being no differences between both groups
      regarding the degree of liver function impairment and tumor stage. Eighty-two
      percent of the patients presented a self-limited postembolization syndrome,
      without treatment-related mortality. Fifty-five percent of the treated cases
      exhibited a partial response, which resulted in a lower probability of tumor
      progression during follow-up (57% vs. 77% at 1 year; P < .005). However, after a
      median follow-up of 24 months (30 deaths in each group), there are no differences
      in survival (Group A: 49% and 13%; Group B: 50% and 27%, at 2 and 4 years,
      respectively; P = .72). The absence of differences was maintained even when
      dividing patients according to Child-Pugh's grade, Okuda stage, or performance
      status test (PST). Furthermore, there were no differences in the probability of
      complications or in the need of hospital admissions. In conclusion, TAE has a
      marked antitumoral effect associated to a slower growth of the tumor, but it does
      not improve the survival of patients with nonsurgical HCC.

PMID- 9620331
TI  - Keratinocyte growth factor protects murine hepatocytes from tumor necrosis factor
      induced apoptosis in vivo and in vitro.
AB  - Keratinocyte growth factor (KGF) promotes epithelial growth and differentiation
      and has potent effects on the liver. The coinjection of lipopolysaccharide (LPS)
      and D-galactosamine (GalN) results in hepatic failure in mice. Mechanistically,
      LPS-induced tumor necrosis factor (TNF) triggers hepatocyte apoptosis, which is
      enhanced by GalN-arrested transcription. Similarly, the combination of TNF and
      actinomycin D (ActD) causes hepatocyte apoptosis in vitro. We studied the effect
      of KGF on LPS and GalN-induced hepatic failure in vivo and on TNF- and ActD
      induced hepatocyte apoptosis in vitro, where it was compared with those of
      hepatic growth factor (HGF) and epidermal growth factor (EGF). Mice treated with
      human recombinant KGF (1 mg/kg subcutaneously) 24 hours before intraperitoneal
      coinjection of LPS and GalN sustained prolonged survival compared with control
      mice, although overall mortality was not changed. The counts of apoptotic
      hepatocytes, serum alanine and aspartate transaminases, and DNA fragments in the
      cytosolic fraction of liver homogenates were higher in control mice than in
      treated mice 6 hours after LPS and GalN coinjection, before any mortality
      occurred. In vitro, hepatocytes pretreated with KGF exhibited reduced TNF- and
      ActD-induced cell damage and DNA fragmentation, similar to hepatocytes pretreated
      with HGF and EGF. In conclusion, KGF prolongs survival during LPS- and GalN
      induced hepatic failure by temporarily protecting hepatocytes against apoptosis.
      It also protects hepatocytes in vitro against TNF- and ActD-induced apoptosis.

PMID- 9620332
TI  - Analysis of the expression pattern of the latent transforming growth factor beta
      binding protein isoforms in normal and diseased human liver reveals a new splice
      variant missing the proteinase-sensitive hinge region.
AB  - Latent transforming growth factor beta binding protein (LTBP), a component of the
      extracellular matrix (ECM) of various tissues, is important for the secretion of
      TGF-beta and, furthermore, for the storage of TGF-beta in ECM. The proteolytic
      cleavage of LTBP is assumed to be the prerequisite for the activation of TGF
      beta. We investigated the mRNA expression pattern of the three LTBP isoforms
      (LTBP-1, -2, -3) and the protein distribution of the components of the large
      latent TGF-beta complex, namely LTBP-1 and -2, latency-associated protein (LAP),
      and TGF-beta, in human liver using reverse-transcription polymerase chain
      reaction (RT-PCR) and immunohistochemical alkaline phosphatase anti-alkaline
      phosphatase (APAAP) staining. Parts of explanted livers diagnosed as hepatitis B,
      hepatitis C, primary biliary cirrhosis (PBC), and primary sclerosing cholangitis
      (PSC) and normal liver tissue were examined. LTBP transcripts were detected in
      the same manner in all liver specimens. Interestingly, we found a new splice
      variant of LTBP-1 (LTBP-1D), in which the sequence coding for the proteinase
      sensitive hinge region is deleted. The corresponding parts of the human LTBP-2
      and LTBP-3 cDNA coding for the hinge region were sequenced and show neither
      similar proteinase cleavage sites nor deleted cDNA sequences. The proposed
      proteinase cleavage site of mouse LTBP-3 seems not to be conserved in the human
      LTBP-3 gene. By immunohistochemistry, LTBP-1, -2, and LAP were detectable in
      normal and diseased livers and showed a different staining pattern for both LTBP
      isoforms. By contrast, TGF-beta showed a spotted staining pattern in diseased
      livers only, predominantly in the area of parenchymal cells that are close to
      fibrotic tissue. This strongly suggests the release of active TGF-beta from
      preexisting latent complexes. The LTBP-1D splice variant, which is probably less
      sensitive against proteolytic degradation and therefore may protect TGF-beta from
      activation, may have importance for modulating the biological activity of TGF
      beta in normal and diseased liver.

PMID- 9620333
TI  - Expression of co-stimulatory molecules by Kupffer cells in chronic hepatitis of
      hepatitis C virus etiology.
AB  - In this paper we show that in viral hepatitis most Kupffer cells (KCs) are
      activated and express high levels of CD80, CD40, and class-II MHC molecules, thus
      acquiring the phenotype of professional antigen presenting cells (APCs).
      Activated KCs display a close contact with CD4+ T lymphocytes and form KCs-T
      lymphocyte clusters. Clusters are found within the sinusoids, across the sinusoid
      wall, and within the liver parenchyma as well, as a consequence of
      transendothelial migration (TEM). The positivity of activated KCs for hepatitis C
      virus (HCV) antigens, which likely reflects phagocytosis of infected hepatocytes,
      suggests that KCs-T cell clusters represent the morphological expression of the
      functional interaction between KCs acting as professional APCs and antigen
      experienced CD4+ T lymphocytes within the liver. These phenotypic and
      morphological changes are distinct features of livers in chronic hepatitis
      patients compared with controls.

PMID- 9620334
TI  - Changes in lymph vessels and portal veins in the portal tract of patients with
      idiopathic portal hypertension: a morphometric study.
AB  - Little is known about the effects of the pathological process associated with
      idiopathic portal hypertension (IPH) on hepatic lymph vessels or lymph flow. We
      used morphometric analysis to examine IPH-associated changes in lymph vessels and
      branches of the portal vein, with use of immunohistochemical staining for alpha
      smooth muscle actin. We also quantitated these changes using an image analysis
      system. The study was conducted with use of liver wedge biopsy material from 10
      patients with advanced IPH and 10 control samples from patients with gastric
      carcinoma without liver disease. The number of lymph vessels, identified by a
      lack of smooth muscle layer in the wall, and the ratio of the total area of these
      vessels to that of the portal tract were higher in IPH samples than in the
      control samples, but the ratio of the area of a single lymph vessel to that of
      the portal tract in IPH samples was not different from control samples. The
      number of portal vein branches, characterized by hypertrophy of the smooth muscle
      layer in IPH samples was not different from control samples. The ratio of the
      total area of these branches to that of the portal tract, and the ratio of a
      single portal vein branch to that of the portal tract, were lower in IPH samples
      than in the control samples. Our results suggest that these morphometric changes
      in IPH may be associated with a reduction in portal blood flow and increased
      lymph flow, and that the latter may in turn reduce the high portal vein pressure
      in idiopathic portal hypertension.

PMID- 9620335
TI  - Hepatic stellate cells are not subjected to oxidant stress during iron-induced
      fibrogenesis in rodents.
AB  - Oxidant stress plays a key role in hepatic fibrogenesis. This study was
      undertaken to assess whether, during iron overload-associated liver fibrosis in
      vivo, oxidant stress occurs in hepatic stellate cells (HSC) during active
      fibrogenesis. Gerbils were treated with iron-dextran, and, after hepatic fibrosis
      developed, livers were subjected to various combination of in situ hybridization
      and immunocytochemistry analyses. In iron-treated animals, no specific
      accumulation of ferritin protein was found in collagen mRNA-expressing cells.
      Moreover, the activity of the iron regulatory protein, the main sensor of
      cellular iron status, was unchanged in HSC from iron-treated animals. Although a
      significant amount of malondialdehyde-protein adducts was detected in gerbil
      liver during fibrogenesis, accumulation of these lipid peroxidation by-products
      was restricted to iron-laden cells adjacent to activated HSC. In cultured gerbil
      HSC, iron, aldehydes, and other pro-oxidants were able to enhance the expression
      of an oxidant stress-responsive gene, heme oxygenase (HO), with no change in
      collagen mRNA accumulation. In keeping with these findings, we found that, in
      vivo, activation of HO gene was present in iron-filled nonparenchymal cell
      aggregates, but absent in HSC. In conclusion, the data indicate that during iron
      overload-associated fibrogenesis, HSC are not directly subjected to oxidant
      stress, but are likely to be activated by paracrine signals arising in
      neighboring cells.

PMID- 9620336
TI  - Complement-mediated cytotoxicity and inhibition of ligand binding to hepatocytes
      by woodchuck hepatitis virus-induced autoantibodies to asialoglycoprotein
      receptor.
AB  - Hepadnavirus invasion in woodchucks has been identified as a potent inducer of
      autoantibodies against asialoglycoprotein receptor (anti-ASGPR), a molecule
      essentially unique to hepatocytes that mediate clearance of desialylated serum
      proteins. We evaluated the possible pathogenetic importance of anti-ASGPR
      triggered by woodchuck hepatitis virus (WHV), using anti-ASGPR-reactive serum
      immunoglobulins (Igs) from five animals with different stages of WHV hepatitis or
      self-limited WHV infection and isolated woodchuck hepatocytes or HepG2 cells as
      targets. The results revealed that WHV-induced anti-ASGPR can specifically
      inhibit asialoglycoprotein recognition by both homologous and heterologous liver
      cells, as tested in an asialofetuin (ASFN)-binding radioassay. However, the
      extent of the interference significantly varied (from 85% inhibition to none) for
      anti-ASGPR with similar titer from different animals, indicating a high degree of
      heterogeneity in the ASGPR epitope specificity and in the potential biological
      effects of these autoantibodies. The WHV-triggered anti-ASGPR also induced
      complement-mediated hepatocytolysis in a microculture tetrazolium (MTT) assay,
      which ranged from 8.9% +/- 0.3% to 33.6% +/- 3.6% (mean +/- SD) for different
      animals and target cell numbers. This cytopathic effect was strictly ASGPR
      specific, complement-dependent, and was not related to the anti-ASGPR ability to
      inhibit ligand-hepatocyte binding. Our findings indicate that among pathways by
      which anti-ASGPR autoimmunity could cause liver damage, hepadnavirus-induced anti
      ASGPR might impair hepatocytes by both disrupting clearance of desialylated
      proteins and activation of the complement-mediated cytolysis. These cytopathic
      effects might contribute to the pathogenesis, aggravate severity, and prolong
      recovery from liver injury in viral hepatitis.

PMID- 9620337
TI  - Fas-mediated apoptosis in mouse hepatocytes involves the processing and
      activation of caspases.
AB  - The mechanism of Fas antigen-induced hepatocyte apoptosis was investigated. Using
      a monoclonal antibody directed against the Fas antigen, apoptosis was induced in
      freshly isolated murine hepatocytes within 90 minutes of antibody addition as
      assessed by plasma membrane bleb formation, chromatin condensation, and DNA
      fragmentation. Pretreatment of the cells with the caspase inhibitors, N-acetyl
      Asp-Glu-Val-Asp aldehyde (Ac-DEVD-CHO), benzyloxycarbonyl-Val-Ala-DL-Asp
      fluoromethylketone (Z-VAD-FMK), or Z-Asp-2,6-dichlorobenzoyloxymethylketone
      inhibited anti-Fas-mediated apoptosis. Likewise, the serine protease inhibitors,
      N-tosyl-L-phenyl chloromethyl ketone (TPCK) and 3,4-dichloroisocoumarin (DCI),
      prevented apoptosis, whereas N-tosyl-L-lysine chloromethyl ketone (TLCK), Ac-Leu
      Leu-L-norleucinal, Ac-Leu-Leu-L-methional, and trans-epoxysuccinyl-L-leucylamido
      (4-guanidino)butane were without effect. Examination of CED-3/caspase-3-related
      caspases revealed that pro-caspases-3 (CPP32) and -7 (Mch-3alpha) were rapidly
      processed after Fas antigen stimulation. Caspase-7 was further cleaved to form
      the catalytically active subunits. In contrast, the p17 subunit of caspase-3 was
      not detected, indicating slow formation or rapid degradation. The activation of
      CED-3-related caspases was further confirmed by an increase in the rate of Z-DEVD
      7-amino-4-trifluoromethylcoumarin (Z-DEVD-AFC) hydrolysis that was sensitive to
      Ac-DEVD-CHO and was inhibited by pretreatment of the cells with TPCK but not by
      DCI. In contrast, no increase in the rates of hydrolysis of Z-YVAD-AFC, a
      substrate for caspase-1, was detected. Investigation of the in situ proteolytic
      cleavage of the CED-3 related caspases substrate, poly(ADP-ribose) polymerase,
      revealed that this protein was not degraded in hepatocytes undergoing Fas
      mediated apoptosis. Taken together, our results show that processing of caspases,
      in particular, caspases-7 and -3, occurs during Fas-induced apoptosis of mouse
      hepatocytes and suggest a role of these proteases as well as serine protease(s)
      in the apoptotic response.

PMID- 9620339
TI  - Apoptosis of sinusoidal endothelial cells is a critical mechanism of preservation
      injury in rat liver transplantation.
AB  - In livers excised for transplantation, sinusoidal endothelium appears especially
      vulnerable to injury during organ preservation in the cold and subsequent
      reperfusion. The degree of endothelial cell injury correlates with functional
      impairment of the graft following transplantation. The mechanism of injury
      remains obscure, but endothelial cell damage has been described as coagulative
      necrosis secondary to irreversible physico-chemical damage. We investigated
      whether endothelial cell death is caused by apoptosis rather than by necrosis.
      Tissue from rat livers stored for varying periods in cold (1 degree C) Euro
      Collins solution and then reperfused for 1 hour at 37 degrees C were studied for
      evidence of apoptosis by detection of DNA fragmentation using the in situ
      terminal deoxynucleotidyl transferase d-uridine triphosphate nick end labeling
      (TUNEL) assay, DNA gel electrophoresis, and by transmission electron microscopy
      (EM). DNA fragmentation of the type characteristic of apoptosis was identified in
      49.7% +/- 2.2% of sinusoidal lining cells after 8 hours of ischemia + reperfusion
      (viable graft) vs. 70.7% +/- 4.3% after 16 hours + reperfusion (nonviable graft)
      (P < .001). No such fragmentation was observed after cold preservation without
      reperfusion or in unpreserved, reperfused livers. EM demonstrated changes
      characteristic of apoptosis exclusively in endothelial cells. The study suggests
      that the apoptosis of sinusoidal endothelial cells is a pivotal mechanism of
      preservation injury in liver transplantation.

PMID- 9620338
TI  - Delayed Fas-mediated hepatocyte apoptosis during liver regeneration in mice:
      hepatoprotective role of TNF alpha.
AB  - Fas-mediated apoptosis is one of the major death processes of hepatocytes in
      liver diseases. Although compensatory regeneration occurs during liver injury, it
      has not been determined whether regenerating hepatocytes die by the same
      apoptotic process as quiescent hepatocytes. To clarify this issue, the hepatocyte
      apoptotic process, after injection of agonistic anti-mouse Fas, was compared
      between sham-operated mice and two-thirds partially hepatectomized mice. The
      onset of hepatocyte apoptosis was retarded in hepatectomized mice, as evidenced
      by both morphological and biochemical observations, resulting in significantly
      prolonged animal survival. Flow cytometric analysis revealed similar levels of
      Fas expression on hepatocytes between hepatectomized mice and sham-operated mice;
      however, the activation of liver caspase-3-like protease after Fas stimulation
      was suppressed in hepatectomized mice, whereas pro-caspase-3 expression did not
      change with or without hepatectomy. Anti-tumor necrosis factor alfa (TNF alpha),
      when administered before hepatectomy, partially reversed suppression of caspase-3
      like activity after Fas stimulation. Furthermore, the injection of TNF alpha into
      untreated mice suppressed caspase-3-like activity and prolonged animal survival
      after Fas stimulation. These results indicate that Fas-signaling events at the
      level or upstream of caspase-3-like protease are suppressed during liver
      regeneration, resulting in delayed hepatocyte apoptosis, and also that TNF alpha
      acts as one of the protective factors against Fas-mediated hepatocyte apoptosis.

PMID- 9620340
TI  - Porphyria cutanea tarda, hepatitis C, and HFE gene mutations in North America.
AB  - In some, but not all countries, porphyria cutanea tarda (PCT) has been associated
      with chronic infection with the hepatitis C virus (HCV). Recently, PCT has also
      been associated with mutations in the HFE gene that are associated with HLA
      linked hereditary hemochromatosis. Until now, few studies of these associations
      have been reported from North America. The aims of this study were: 1) to assess
      the prevalence of HCV infection and HFE mutations in North American patients with
      PCT; 2) to compare demographic and laboratory features between those who are HCV
      positive and HCV-negative; and 3) to study urinary porphyrin excretions in
      American HCV-positive patients without clinically manifest PCT. Clinical and
      laboratory data, including tests for HCV and urinary porphyrins, were collected
      from 70 unselected patients with typical PCT. Urinary porphyrins were also
      measured in 110 non-PCT patients with chronic hepatitis C. Mutational analyses of
      the HFE gene were performed in 26 PCT patients. Thirty-nine of 70 (56%) of the
      PCT patients had evidence of HCV infection. Thirty-two of 39 PCT patients with
      HCV were men, all of whom used alcohol. In contrast, 22 of 31 PCT patients
      without HCV infection were women, 12 of whom had taken estrogens. The HCV
      positive group was more likely to have used illicit intravenous drugs (45% vs.
      0%; P = 0.01), to have had several (>4) sex partners (48% vs. 13%; P = 0.005),
      and less likely to have no known risk factors for HCV infection (33% vs. 78%; P =
      0.004). Total urinary porphyrin excretion was the same in the two groups, but
      those with HCV infection had a significantly lower percentage of uroporphyrin and
      higher percentages of hepta-and hexa-carboxy porphyrins in urine. Sixteen of 110
      (15%) HCV-positive subjects without PCT had increased urinary porphyrins, but,
      unlike PCT, these were mainly coproporphyrin. Forty-two percent of PCT patients
      carried the C282Y mutation of HFE (15% homozygous), and another 31% carried the
      H63D mutation (8% homozygous). Thus, 73% of PCT patients had one of these
      mutations. The prevalence of HCV infection (56%) and mutations in the HFE gene
      (73%) are high among North American patients with PCT. Alcohol and estrogen use
      are important additional risk factors. All PCT patients should be tested for HCV
      infection and for HFE gene mutations. Although HCV infection is a trigger for
      PCT, preclinical PCT is rare in chronic HCV hepatitis C in the United States.

PMID- 9620341
TI  - Identification and characterization of mutations in hepatitis B virus resistant
      to lamivudine. Lamivudine Clinical Investigation Group.
AB  - Cirrhosis and hepatocellular carcinoma occur as long-term complications of
      chronic hepatitis B virus (HBV) infection. Antiviral therapy is potentially a
      successful approach for the treatment of patients with HBV infection, which
      includes the nucleoside analog, lamivudine [(-)2'-deoxy-3'-thiacytidine, 3TC].
      Although resistance to lamivudine therapy has been reported in several HBV
      infected patients, the pattern of resistance-associated mutations in HBV has not
      been fully characterized. We report a DNA sequence database that includes a 500
      base pair region of the HBV polymerase gene from 20 patients with clinical
      manifestations of lamivudine resistance. Analysis of the database reveals two
      patterns of amino acid substitutions in the tyrosine, methionine, aspartate,
      aspartate (YMDD) nucleotide-binding locus of the HBV polymerase. HBV DNA from the
      sera of patients in Group I exhibits a substitution of valine for methionine at
      residue 552, accompanied by a substitution of methionine for leucine at residue
      528. Patients in Group II had only an isoleucine-for-methionine substitution at
      position 552. Reconstruction of these mutations in an HBV replication-competent
      plasmid was performed in a transient transfection cell assay to determine the
      function/relevance of these mutations to lamivudine resistance. Both Group I and
      Group II mutations resulted in a substantial decrease in sensitivity to
      lamivudine treatment (> 10,000-fold shift in IC50 over wild-type [wt] IC50),
      strongly indicating that these mutations were involved in resistance to
      lamivudine. A hypothetical model of the HBV reverse transcriptase has been
      generated for further study of the role of these mutations in lamivudine
      resistance.

PMID- 9620342
TI  - Dynamics of hypervariable region 1 variation in hepatitis C virus infection and
      correlation with clinical and virological features of liver disease.
AB  - Hepatitis C virus (HCV) infection is a dynamic process during which molecular
      variants are continuously selected as the result of virus adaptation to the host.
      Understanding the nature of HCV genetic variation is central to current theories
      of pathogenesis and immune response. We prospectively studied hypervariable
      region 1 (HVR1) variation in the E2 gene of 36 hepatitis C patients, including 10
      asymptomatic carriers, followed up for 1 to 2 years. Sequence changes in single
      and consecutive serum samples were assessed and correlated with clinical and
      virological parameters of liver disease. A region of the E1 gene was sequenced
      for comparison in 3 subjects. HVR1 heterogeneity at single time points widely
      varied in individual patients, did not increase cumulatively over the follow-up
      period, and did not correlate with HVR1 evolutionary rates. Conversely, the
      process of HVR1 sequence diversification, although differed considerably among
      patients, was stable over time and directly correlated with infections by HCV
      type 2, lower alanine aminotransferase (ALT) levels, and absence of cirrhosis.
      HCV carriers showed the highest HVR1 variation rates. Our findings indicate that
      HVR1 variation has an adaptive significance and is associated with favorable
      features of liver disease and suggest that prospective, rather than static,
      observations are required to model the process of HCV variation.

PMID- 9620343
TI  - Ribavirin inhibits protein synthesis and cell proliferation induced by mitogenic
      factors in primary human and rat hepatocytes.
AB  - Ribavirin, a guanosine analog, used in combination with interferon alpha (IFN
      alpha) in the treatment of chronic hepatitis induced by hepatitis C virus (HCV)
      infection, has been shown to improve liver histology and to decrease
      transaminases even when administered alone. We analyzed the direct effects of
      ribavirin on the liver by using primary cultures of human and rat hepatocytes.
      Between 10 to 60 micromol/L, ribavirin was found to inhibit both the synthesis
      and secretion of whole proteins in a time- and dose-dependent fashion. Such an
      effect was confirmed by the measurement of albumin and haptoglobin secretion
      rates. [3H]-Thymidine incorporation was suppressed both in hepatocyte growth
      factor-stimulated human hepatocytes and in epidermal growth factor (EGF)
      stimulated rat hepatocytes in the presence of ribavirin. The inhibitory effect on
      DNA synthesis was associated with a delayed progression to S phase of the cell
      cycle, as determined by flow cytometry and detection of cyclin A and cdc2 which
      are two proteins expressed during the S phase. The inhibition of DNA synthesis,
      caused by 50 micromol/L ribavirin, was completely restored by the addition of 80
      micromol/L guanosine. These observations demonstrate that ribavirin at
      concentrations close to those found in plasma of treated patients can directly
      affect hepatic functions in vitro. Its effects could, however, be reduced in vivo
      by guanosine salvage supply.

PMID- 9620344
TI  - Heterozygosity for hereditary hemochromatosis is associated with more fibrosis in
      chronic hepatitis C.
AB  - Hepatic iron has been associated with more aggressive liver disease in chronic
      viral hepatitis. We evaluated whether the recently described C282Y mutation of
      the hemochromatosis gene, designated HFE (responsible for at least 83% of
      hereditary hemochromatosis), was associated with more advanced liver disease in
      chronic hepatitis C. One hundred thirty-seven patients with biopsy-proven chronic
      hepatitis C were studied and liver biopsies scored for necroinflammation (grade 0
      18) and fibrosis (stage 0-6). Genomic DNA was amplified by polymerase chain
      reaction and the C282Y mutation identified by restriction with RsaI and
      electrophoretic separation of restriction fragments. Ten (7.3%) patients had the
      C282Y mutation. No C282Y homozygous patients were identified. Age, sex
      distribution, and estimated weekly alcohol consumption were not significantly
      different between those with and without the mutation. Serum ferritin was higher
      in the heterozygotes (mean, 339 microg/L) compared with homozygous wild types
      (153 microg/L; P = .0005). In the majority of patients, liver iron was graded 0
      out of 4, but hepatocyte iron staining was more commonly present in heterozygotes
      compared with homozygous normals (30% compared with 4% [P = .02]). Liver disease
      was more advanced in those with the mutant allele (mean fibrosis stage: 3.6,
      compared with wild type: 1.5 [P = .01]). Cirrhosis was found more often in those
      with the mutation (40%) compared with those without (8.7%) (P = .01; odds ratio:
      7.6 [1.9-31.2]). There was no significant difference in inflammation scores
      between heterozygotes and wild type (mean, 5.4 compared with 4.1). Hepatitis C
      virus (HCV)-RNA titers were measured by branched DNA assay (HCV RNA 2.0-Chiron),
      and there was no difference between heterozygous and homozygous normal patients.
      Thus, despite relatively minor increases in iron stores, individuals who are
      heterozygous for hemochromatosis appear to develop more fibrosis in chronic
      hepatitis C. Venesection may be useful therapy in this subgroup.

PMID- 9620345
TI  - What strategy should be used for diagnosis of hepatitis C virus infection in
      clinical laboratories?
AB  - The aim of this study was to determine a cost-effective strategy for the
      diagnosis of hepatitis C virus (HCV) infection in clinical laboratories. Anti-HCV
      antibodies were sought in 3,014 consecutive unselected samples with two different
      enzyme-linked immunosorbent assays (ELISA). An immunoblot-based confirmatory
      assay (RIBA3.0) was performed in the samples with at least one ELISA positive or
      weakly positive. HCV RNA was evaluated using HCV polymerase chain reaction (PCR)
      in the samples with a weakly positive ELISA, discrepant results of the two
      ELISAs, or an indeterminate RIBA3.0 pattern. The two ELISAs gave concordant
      results in 2,957 (98.1%) of the 3,014 samples (negative in 87.9%, positive in
      11.8%, and weakly positive in 0.3%), and discrepant results in 57 (1.9%). RIBA3.0
      was positive in 338 of the 350 ELISA-positive samples (96.6%) and indeterminate
      in 12. Six of them were PCR-positive. Among the 8 weakly positive samples, 1 was
      RIBA3.0-positive, 6 were RIBA3.0-indeterminate, and 1 was RIBA3.0-negative; all
      were PCR-negative. Among the 57 samples with discrepant ELISA results, 4 were
      RIBA3.0-positive (none were PCR-positive), 22 were RIBA3.0-indeterminate (1 was
      PCR-positive), and 31 were RIBA3.0-negative (6 were PCR-positive). In these
      cases, the clinical context and PCR detection of HCV RNA allowed for definitive
      classification. In conclusion, one single ELISA determination is necessary for
      diagnosis of HCV infection in clinical laboratories, and confirmation of positive
      or weakly positive ELISAs with immunoblot-based confirmatory assays is no longer
      needed. HCV-RNA detection by PCR helps to resolve weakly positive or negative
      ELISA results when the clinical context is compatible with hepatitis C.

PMID- 9620346
TI  - Broadly reactive antibodies to hypervariable region 1 in hepatitis C virus
      infected patient sera: relation to viral loads and response to interferon.
AB  - To clarify the nature of serum anti-hypervariable region 1 (HVR1) antibodies in
      patients infected with hepatitis C virus (HCV), we assessed the reactivity of 21
      patients' sera with 42 HVR1 proteins by Western blot. HVR1 was expressed as
      fusion proteins with glutathione S-transferase (GST). The patients' sera reacted
      with variable percentages of the HVR1 proteins, and always reacted with HVR1
      proteins of the different genotype. In the genotype-1b-infected patients, the
      percentage of genotype-1b HVR1 proteins reactive with serum correlated
      significantly with viral loads; the sera reactive with the higher percentages of
      HVR1 proteins contained the larger viral loads. In addition, it was significantly
      lower in the responders of interferon (IFN) therapy than in nonresponders. The
      competition assays indicated that multiple fractions of anti-HVR1 antibodies with
      different specificity in a serum reacted with different HVR1 proteins, and that,
      additionally, a single fraction of antibodies often reacted with more than one
      HVR1 protein through a similar amino acid sequence. In conclusion, serum anti
      HVR1 antibodies were broadly reactive by the mechanism of both the cross
      reactivity of a single fraction of anti-HVR1 antibodies with more than one HVR1
      protein and the presence of multiple fractions of anti-HVR1 antibodies with
      different specificity in a serum. In genotype-1b-infected patients, the broad
      reactivity of serum anti-HVR1 antibodies correlated with viral loads and response
      to IFN. Further studies are necessary to elucidate the correlation among the
      broad reactivity of sera with multiple HVR1 proteins and clinical features of
      chronic hepatitis C patients.

PMID- 9620347
TI  - Emergence and takeover of YMDD motif mutant hepatitis B virus during long-term
      lamivudine therapy and re-takeover by wild type after cessation of therapy.
AB  - Treatment of hepatitis B virus (HBV) with lamivudine is effective in suppressing
      virus replication and results in reduced inflammatory activity. However, the
      emergence of lamivudine-resistant mutant virus, with amino acid substitution in
      the YMDD motif of DNA polymerase, has been reported. We report the emergence and
      takeover of YMDD mutant and re-takeover by wild type during and after long-term
      lamivudine therapy. YMDD mutants were detected in five patients who showed DNA
      breakthrough (HBV DNA becoming detectable after a period of DNA negativity),
      which occurred after 9 to 14 months of lamivudine therapy. Four of five mutants
      had amino acid sequence YIDD, and the remaining mutant had YVDD. Patients with
      high HBV-DNA titer and/or hepatitis B e antigen tended to develop breakthrough (P
      = .038). Using a sensitive and specific polymerase chain reaction (PCR)-based
      method developed in this study, the emergence of YMDD mutants was detected 1 to 4
      months before DNA breakthrough, but not detected in any of the pretreatment sera.
      The mutants were predominant at breakthrough, but were replaced by wild-type
      virus 3 to 4 months after cessation of therapy in the two patients who
      discontinued therapy. One of these patients had a relapse of hepatitis. Mutant
      continued to replicate in the remaining three patients who continued to receive
      treatment, and relapse occurred in only one of these patients. Our results
      suggest that the replication of YMDD mutant viruses is less than wild type and is
      re-overtaken by wild type after cessation of therapy. Re-administration of
      lamivudine, possibly combined with other antiviral therapy, might be useful in
      some patients experiencing hepatitis with lamivudine-resistant variants.

PMID- 9620348
TI  - Effect of alcohol consumption on serum hepatitis C virus RNA and histological
      lesions in chronic hepatitis C.
AB  - The role of alcohol intake in the occurrence of severe liver disease in chronic
      hepatitis C virus (HCV) carriers is still debated. A cross-sectional study has
      been conducted in 233 chronic hepatitis C virus carriers. Weekly self-reported
      alcohol consumption (SRAC) was evaluated, serum HCV RNA levels were measured by a
      branched DNA technique (Quantiplex 2.0) and HCV genotypes were determined. A
      liver biopsy was performed simultaneously and liver lesions were graded with the
      Knodell histological activity index. Data were examined by uni- and multivariate
      analyses. Alcohol consumption was relatively low (< 140 g/per week in 193/233
      patients [80%]). We found a highly significant correlation between SRAC and serum
      HCV RNA levels (r = .26, P = .001). Fibrosis was significantly correlated with
      age and alcohol consumption. These results suggest that in HCV carriers, alcohol
      consumption, even with low alcohol intake, increases viremia and hepatic
      fibrosis. Chronic HCV carriers should be advised to avoid regular alcohol intake.

PMID- 9620349
TI  - Hepatitis D viremia following orthotopic liver transplantation involves a typical
      HDV virion with a hepatitis B surface antigen envelope.
AB  - Patients receiving orthotopic liver transplantation (OLT) because of type D
      hepatitis frequently exhibit what appears to be an autonomous, or "isolated,"
      hepatitis D virus (HDV) infection following the transplantation, with no evidence
      of hepatitis B virus (HBV) in the graft or in the serum. These observations have
      led to the hypothesis that HBV might not always be required for HDV infection, or
      that HDV could exist as a latent infection until rescued by HBV. Alternatively,
      an apparently autonomous HDV infection could be explained by coinfection of a
      small number of hepatocytes with both viruses following transplantation, with a
      very low level of HBV expression that supports low-level HDV propagation. Our
      results are consistent with the latter hypothesis. Sensitive polymerase chain
      reaction (PCR)-based analysis of HBV and HDV viremia in transplantation patients
      with HDV infection previously characterized as isolated showed that HDV viremia
      was not independent of HBV viremia. Additional analyses, including PCR
      amplification, buoyant density analysis in a CsCl gradient, and
      immunoprecipitation with monoclonal hepatitis B surface antigen antibodies (anti
      HBs), indicated that the posttransplant HDV particle is typical: it contains full
      length HDV RNA and an envelope of hepatitis B surface antigen (HBsAg) and is not
      different from that found during the acute and chronic stages of HDV
      superinfection or coinfection. Moreover, an experimental test of the first
      hypothesis in chimpanzees did not support the idea that HDV can persist for
      several weeks as an isolated, latent infection that can be rescued subsequently
      by HBV. The data indicate, therefore, that latent HDV infection is not a factor
      in OLT recipients. We conclude that the HDV virion in the posttransplantation
      setting is typical, and that HDV viremia following OLT requires the helper
      function of HBV infection.

PMID- 9620350
TI  - Role of alcohol in the progression of liver disease caused by hepatitis C virus
      infection.
AB  - In patients with chronic hepatitis C, alcohol consumption has been proposed as a
      risk factor for the progression of liver disease; however, evidence for this
      remains conflicting. Two hundred thirty-four anti-hepatitis C virus (HCV)
      positive patients who had a liver biopsy performed within the past 24 months were
      studied. Demographic data and information on risk factors were recorded. A
      detailed lifetime alcohol consumption history was obtained. Viral studies
      included HCV viral titer and HCV genotype. Mean age (+/- SEM) of the group was
      40.8 +/- 0.7 years. One hundred sixty-six (71%) were male. A risk factor for HCV
      infection was found in 195 patients (86%). Genotype distribution was: 1b: 22%;
      1a: 15%; 1(nonsubtypable): 15%; 3a: 34%; and 2: 7%. Fifty (21%) patients had
      cirrhosis. Patients with cirrhosis were older (51.6 +/- 1.8 years) than those
      with chronic hepatitis (37.6 +/- 0.6 years; P = .0001), were infected at an older
      age (25.9 +/- 2.0 vs. 20.9 +/- 0.6 years; P = .001), and had a longer duration of
      infection (20.5 +/- 1.3 vs. 16.2 +/- 0.5 years; P = .0008). Patients with
      cirrhosis had a greater total lifetime alcohol consumption (288,765 +/- 58,115 g)
      than those with chronic hepatitis (189,941 +/- 15,453 g; P = .018). Cirrhotic
      patients also had greater total alcohol consumption during the period of
      infection with HCV (240,962 +/- 63,756 g vs. 146,510 +/- 12,862 g; P = .02). On
      multivariate analysis, subject age and total alcohol consumption were
      independently associated with the presence of cirrhosis. Total lifetime alcohol
      consumption is a risk factor for the progression of liver disease caused by HCV.

PMID- 9620351
TI  - Molecular basis for persistent hepatitis B virus infection in the liver after
      clearance of serum hepatitis B surface antigen.
AB  - Hepatitis B virus (HBV) DNA has been detected by polymerase chain reaction (PCR)
      in the liver of patients with resolved chronic HBV infection and sustained
      clearance of hepatitis B surface antigen (HBsAg) from serum. However, it is
      unknown whether the virus is transcriptionally active at this time or if the
      covalently closed circular (CCC) replicative intermediate of HBV DNA can still be
      detected. Therefore, hepatic nucleic acid extracts from seven patients who had
      cleared serum HBsAg were assessed by (PCR) for either reverse-transcribed HBV
      RNA, or an intact direct repeat region of the HBV genome indicative of the CCC
      replicative intermediate of HBV DNA. HBV transcripts were detected in four of
      seven patients in the study group, whereas an intact direct repeat region of the
      HBV genome was detected in three. Evidence for viral transcription and
      replication was more frequently detected in patients who had recently cleared
      serum HBsAg, but HBV RNA was also detected in one patient 5 years after HBsAg
      clearance, and an intact direct repeat region of HBV DNA was detected in another
      subject at nearly 4 years after resolution of disease. Therefore, hepatic HBV
      transcription may be associated with replicative intermediates of persistent HBV
      DNA in patients who have cleared HBsAg from serum, suggesting that, on occasion,
      HBV may not be in a latent state but undergoing low-level replication.

PMID- 9620352
TI  - Transcatheter arterial embolization for advanced hepatocellular carcinoma: the
      controversy continues.

PMID- 9620353
TI  - Does altered regulation of ecNOS in sinusoidal endothelial cells determine
      increased intrahepatic resistance leading to portal hypertension?

PMID- 9620354
TI  - Does prophylactic ursodeoxycholic acid treatment of liver transplant patients
      prevent acute rejection?

PMID- 9620355
TI  - The glycosylation heterogeneity of recombinant human IFN-gamma.
AB  - The cloning of the cDNA for human interferon-gamma (IFN-gamma) has resulted in
      its expression in Escherichia coli, baculovirus-infected insect cells, Chinese
      hamster ovary (CHO) cells, and the mammary gland of transgenic mice. Large
      quantities of highly purified recombinant IFN-gamma have been generated, aided by
      the use of highly specific neutralizing monoclonal antibodies, with a view to its
      production as a human therapeutic protein. The primary source of structural
      heterogeneity for IFN-gamma during its production in mammalian expression systems
      is glycosylation, which can profoundly affect the three-dimensional structure of
      a glycoprotein and its biological function. A number of analytical approaches
      have been developed recently to allow a detailed analysis of the carbohydrate
      structures associated with IFN-gamma, the principal advances being in the areas
      of capillary electrophoresis and mass spectrometry. The implementation of these
      high-resolution analytical tools to determine the glycosylation profile of IFN
      gamma makes it one of the best characterized recombinant glycoproteins.
      Recombinant human IFN-gamma acts as a model secretory glycoprotein, typifying the
      intrinsic glycosylation processing events associated with production of a
      potential therapeutic glycoprotein.

PMID- 9620356
TI  - M150 modulates the costimulatory signals delivered by B cells to T cells and
      enhances their ability to help B cells.
AB  - There is a prerequirement of at least two sets of signals delivered by the
      antigen-presenting cell (APC) for the optimal activation of T helper (Th) cells.
      The first signal is provided by the engagement of T cell receptor with the
      antigen-MHC class II complex, followed by a second stimulus in the form of
      costimulatory signals. In the present study, we provide evidence that in a T
      dependent antigen-driven system, the signals generated by hapten-specific B cells
      to stimulate Th cells for the secretion of interleukin-2 (IL-2), interferon-gamma
      (IFN-gamma), and IL-4 were differentially modified by M150, a 150-kDa molecule
      expressed on the surface of macrophages. When ovalbumin-specific Th cells were
      cultured in the presence of 2,4,6 trinitrophenol (TNP)-specific B cells, M150
      significantly increased the proliferation of Th cells and the secretion of IL-2
      and IFN-gamma and decreased the production of IL-4. Further, Th cells stimulated
      with M150 acquired improved ability to help B cells, resulting in an increase in
      the number of antibody-secreting cells and in the production of TNP-specific
      IgG2a antibodies. M150 possibly promotes Th1-like cell activity, as evidenced by
      predominant secretion of IL-2, IFN-gamma, and IgG2a but not IL-4 and IgG1.

PMID- 9620357
TI  - Construction and characterization of encapsidated poliovirus replicons that
      express biologically active murine interleukin-2.
AB  - Poliovirus genomes have been constructed in which the capsid genes have been
      substituted with the murine gene encoding interleukin-2 (IL-2) (referred to as
      replicons). One replicon contained the gene for IL-2 in place of the poliovirus
      capsid VP2 and VP3 genes, and a second replicon was constructed that contained
      the murine IL-2 substituted for the poliovirus VP3 and VP1 genes. The IL-2 genes
      were cloned into the replicon so as to maintain the translational reading frame
      with the remaining poliovirus proteins. Transfection of either replicon into
      cells resulted in the expression of replicon-encoded proteins and replication of
      replicon RNA. Using a procedure developed in this laboratory, we have
      encapsidated these replicons into authentic polio virions by passaging the
      replicons in the presence of a recombinant vaccinia virus, VVP1, which expresses
      the capsid precursor, P1, protein. Using a quantitative immunoassay, we
      determined that the majority of the IL-2 produced remained intracellular, with
      approximately 1%-2% released from the infected cells, and that the IL-2 was
      biologically active. The results of these studies demonstrate the utility of
      poliovirus replicons for expression of small bioactive molecules and are
      discussed with respect to future applications as immune adjuvants as well as
      potential new tumor therapies.

PMID- 9620358
TI  - Differential expression of p53 tumor suppressor protein and IL-2 in activated T
      cells from elderly humans.
AB  - Aging is associated with a decline in T cell proliferative responses and
      aberrations in cytokine production. In the present study, we examined if aging
      might alter the expression of the tumor-suppressor protein p53 and the
      retinoblastoma susceptibility gene product (Rb) as well as the levels of Bcl-2 in
      resting and activated human T cells. No significant differences were observed in
      the basal levels of p53 protein among resting T cells from young and elderly
      humans. After stimulation with anti-CD3 monoclonal antibody (mAb) OKT3 and
      phorbol myristate acetate (PMA), T cells from young humans exhibited severalfold
      increases in p53 protein expression compared with resting T cells. By contrast, T
      cells from a substantial portion of elderly humans failed to demonstrate
      significant increases in p53 in response to anti-CD3 plus PMA. No age-related
      alterations in the levels of Rb or Bcl-2 proteins were observed in resting or
      anti-CD3/PMA-stimulated T cells. To delineate whether the age-related reductions
      in p53 expression might be linked to decreased interleukin-2 (IL-2) production,
      we compared the expression of p53 and IL-2 in anti-CD3/PMA-stimulated T cells
      from elderly people. The results showed that impaired induction of p53 expression
      in activated T cells from certain elderly people could be observed without
      considerable impairments in IL-2 production. These observations suggest that age
      related reductions in T cell expression of p53 may contribute to the decline of T
      cell competence independent of the impairments in IL-2 production.

PMID- 9620359
TI  - Phase I/II trial of the type I soluble recombinant human interleukin-1 receptor
      in HIV-1-infected patients.
AB  - Interleukin-1 (IL-1) produced in peripheral blood mononuclear cell (PBMC)
      cultures or added exogenously has been shown to upregulate HIV expression in
      vitro. Inhibition of IL-1 in HIV-infected individuals may inhibit HIV activation
      and slow disease progression. Recombinant human IL-1 receptor (rHu-IL-1R), the
      soluble extracellular portion of the human type I IL-1 receptor, inhibits HIV
      expression in acutely infected primary PBMCs and in the chronically infected
      promonocytic cell line, U1. We, therefore, conducted a phase I/II trial of the
      soluble rHu-IL-1R in HIV-1-infected individuals with CD4 T cell counts
      <300/microl to evaluate its safety and activity. Twelve evaluable patients were
      enrolled at three rHu-IL-1R dose levels:125 (n=3), 500 (n=3), and 1250 (n=6)
      microg/m2 per dose by subcutaneous (s.c.) injection three times a week for 8
      weeks, followed by a 4 week observation period. rHu-IL-1R was safe and well
      tolerated. There were no deaths, no treatment-related grade 3/4 events, and no
      premature study discontinuations because of adverse events. The maximum tolerated
      dose was not reached. Seven patients reported improvements in one or more
      symptoms, including weight gain (3), improved energy level (4), decreased
      diarrhea (1), decreased night sweats (1), improvement in psoriatic arthritis (1),
      and improvement in a nonspecific chronic diffuse skin rash (1). Of 3 evaluable
      patients with Kaposi's sarcoma, 1 remained stable and 2 showed minimal
      progression. No consistent trends in absolute CD4 counts or percentages,
      quantitative HIV cultures, or serum p24 antigen, beta2-microglobulin, or
      triglyceride levels were observed. rHu-IL-1R is safe and well tolerated at the
      doses tested but induced no consistent changes in objective markers of HIV
      disease. Symptomatic improvements will require confirmation in randomized,
      placebo-controlled trials.

PMID- 9620360
TI  - Molecular markers of hemostatic activation and inflammation following major
      injury: effect of therapy with IFN-gamma.
AB  - Interferon-gamma (IFN-gamma) has shown promise in treatment of injured patients.
      However, reactive states marked by immunologic and inflammatory responses
      constitute a potential deleterious effect of IFN-gamma administration. IFN-gamma
      therapy has been associated with high levels of tumor necrosis factor-alpha (TNF
      alpha), with potential enhancement of coagulopathy after injury. This study
      evaluated TNF-alpha production and markers of hemostatic activation in patients
      receiving IFN-gamma therapy. Seventy-three patients, part of a larger multicenter
      trial, with severe injuries were randomized to IFN-gamma (100 microg/day s.c. for
      21 days) or placebo treatment. Enrollment criteria included injury severity score
      (ISS) > or = 25 or significant bacterial contamination with ISS > or = 20. TNF
      alpha and other cytokine production was assessed at baseline and on days 3, 8,
      and 22 following injury. Markers of coagulation activation and fibrinolysis were
      also evaluated. Plasma TNF-alpha and interleukin-6 (IL-6) levels were higher in
      IFN-treated relative to placebo-treated patients before and after IFN
      administration. Markers of coagulation and fibrinolysis were elevated at all
      times studied following injury in both treatment and control groups but did not
      differ between patients receiving IFN and those receiving placebo. Activation of
      coagulation and fibrinolysis diminished in a time-related manner following
      injury. We conclude that (1) IFN-gamma therapy at the dose employed was not
      associated with a significant increase in TNF-alpha or other inflammatory
      cytokine production beyond that seen in patients receiving placebo, (2)
      coagulation and fibrinolytic markers were increased following injury but
      decreased significantly in surviving patients, and (3) no changes in coagulation
      and fibrinolytic parameters were noted in relation to IFN-gamma therapy. These
      findings support previous observations that trauma is associated with hemostatic
      activation and that treatment of patients at the dose of IFN-gamma studied is
      safe in the setting of injury.

PMID- 9620361
TI  - Induction of spermidine/spermine N1-acetyltransferase by interferon type I in
      cells of hematopoietic origin.
AB  - A number of novel genes activated by type I interferons (IFNs) were identified by
      differential display. Of five induced genes examined, four were of unknown
      function. However, one gene sequence was identical to the human
      spermidine/spermine N1-acetyltransferase, the rate-limiting enzyme in polyamine
      catabolism. This enzyme was induced by type I IFNs in a series of hematopoietic
      cell lines, including Daudi, HL-60, HPBMa, and Wil-2. No induction above
      constitutive levels occurred in a cell line of epithelial (ME180) or liver
      (HepG2) origin following treatment with type I IFN. Spermidine/spermine N1
      acetyltransferase was not induced by IFN-gamma in Daudi or ME180 cells. That
      induction occurred not only at the level of transcription but also at the enzyme
      level was confirmed by direct enzyme assays. As the levels of polyamines are
      related to cell viability, we propose that induction of this enzyme by IFN may be
      directly related to the anti-proliferative response to type I IFNs.

PMID- 9620362
TI  - Development of neutralizing antibodies in patients with relapsing-remitting
      multiple sclerosis treated with IFN-beta1a.
AB  - Sixty-eight patients with relapsing-remitting multiple sclerosis (RRMS) were
      treated with 3 million or 9 million i.u. of recombinant interferon-beta1a (recIFN
      beta1a) s.c. three times a week for 2 years. Their sera were tested for
      antibodies neutralizing the IFN (NAb) in a bioassay. Sera with titers > or = 1:20
      were considered positive. We detected NAb in 3.2%, 13.8%, and 15.9% of the
      patients in sera obtained at 3, 6, and 24 months, respectively. The incidence was
      not related to the IFN dose. Interestingly, during the 6 month baseline period
      before the start of the study, relapse rates, baseline disability, and the volume
      of lesions on T2-weighted images were significantly higher in patients who
      developed NAb during treatment. Because of interpatient variability, no
      definitive relationship was observed between NAb formation and loss of clinical
      or magnetic resonance imaging (MRI) response.

PMID- 9620363
TI  - Mapping interleukin enhancer binding factor 3 gene (ILF3) to human chromosome 19
      (19q11-qter and 19p11-p13.1) by polymerase chain reaction amplification of human
      rodent somatic cell hybrid DNA templates.
AB  - Interleukin-2 (IL-2) is the first lymphokine secreted following T cell
      activation. Several transcription factors regulate IL-2 gene expression,
      including the nuclear factor of activated T cells (NFAT). NFAT acts at the
      antigen receptor response element-2 (ARRE-2) sequence in the IL-2 enhancer and is
      the nuclear target of T cell stimulation signals and the immunosuppressant drugs
      cyclosporine (Sandimmune) and FK-506 (tacrolimus), which are potent inhibitors of
      IL-2 gene transcription. NFAT has been cloned and found to consist of two
      subunits, NF45 (ILF2) and NF90 (ILF3). We have recently assigned the gene
      encoding the small NFAT subunit, NF45 (ILF3) to human chromosome 1 (1q11-qter and
      1p11-p12). This communication reports the assignment of the gene encoding the
      large NFAT subunit, NF90 or interleukin enhancer binding factor 3 gene (ILF3), to
      human chromosome 19 (19q11-qter and 19p11-p13.1) by polymerase chain reaction
      (PCR) amplification of ILF3-specific DNA sequences from well-characterized human
      rodent somatic cell hybrid DNAs.

PMID- 9620364
TI  - Determinations of levels of human immunodeficiency virus type 1 RNA in plasma:
      reassessment of parameters affecting assay outcome. TUBE Meeting Workshop
      Attendees. Technology Utilization for HIV-1 Blood Evaluation and Standardization
      in Pediatrics.

PMID- 9620365
TI  - Immunodiagnosis of human granulocytic ehrlichiosis by using culture-derived human
      isolates.
AB  - Human granulocytic ehrlichiosis (HGE) is an emerging infection caused by an
      Ehrlichia species closely related to Ehrlichia equi and Ehrlichia phagocytophila.
      Recent advances in the isolation and cultivation of this organism have allowed us
      to develop an immunofluorescence assay (IFA), enzyme immunoassay (EIA), and
      Western immunoblotting (WB) using HL-60 cell culture-derived human isolates.
      Antibody was detected in sera from culture-confirmed HGE patients by IFA and EIA,
      and these samples were reactive when analyzed by immunoblot analysis. HGE patient
      sera had high antibody titers and did not react with uninfected HL-60 cells. When
      IFA, EIA, and WB were used to analyze sera from healthy donors or those with a
      range of other disorders, including infections caused by Ehrlichia chaffeensis,
      Rickettsia rickettsii, and Coxiella burnetti, no significant cross-reactivity
      could be detected by EIA or immunoblot analysis with the exception of two of four
      serum samples from R. rickettsii-infected patients that were reactive by IFA
      only. Sera from HGE patients did not significantly cross-react in serologic tests
      for Borrelia burgdorferi. Using sera from patients previously enrolled in two
      clinical trials of treatment for early Lyme disease, we evaluated a two-step
      approach for estimation of the seroprevalence of antibodies reactive with the
      etiologic agent of HGE. On the basis of the immunoblot assay results for sera
      from culture-confirmed HGE patients, WB was used to confirm the specificity of
      the antibody detected by EIA and IFA. EIA was found to be superior to IFA in the
      ability to detect WB-confirmed antibodies to the HGE agent. When EIA and WB were
      used, 56 (19.9%) patients with early Lyme disease (n = 281) had either specific
      immunoglobulin M (IgM) or IgG antibodies; 38 patients (13.5%) had IgM only, 6
      (2.1%) had IgG only, and 12 (4.3%) had both IgM and IgG. Therefore, Lyme disease
      patients are at high potential risk for exposure to Ehrlichia. Analysis by
      immunoblotting of serial samples from persons with culture-confirmed HGE or
      patients with Lyme disease and antibodies to the agent of HGE revealed a
      reproducible pattern of the immune response to specific antigens. These samples
      confirmed the importance of the 42- to 45-kDa antigens as early, persistent, and
      specific markers of HGE infection. Other significant immunogenic proteins appear
      at 20, 21, 28, 30, and 60 kDa. Use of the two-test method of screening by EIA and
      confirming the specificity by WB appears to offer a sound approach to the
      clinical immunodiagnosis of HGE.

PMID- 9620366
TI  - Comparison of performances of two commercially available tests, a PCR assay and a
      ligase chain reaction test, in detection of urogenital Chlamydia trachomatis
      infection.
AB  - The diagnostic performance of a PCR test (Roche Cobas Amplicor CT/NG Test) and
      that of a ligase chain reaction (LCR) test (Abbott LCx Chlamydia trachomatis
      assay) were compared by using endocervical and urethral swab specimen culture as
      a reference test. First-void urine (FVU) and endocervical and urethral swab
      specimens were collected from 1,015 unselected patients attending a sexually
      transmitted disease clinic and a clinic for adolescents in Helsinki, Finland.
      Chlamydia trachomatis was cultured from samples from the endocervix or urethra.
      PCR was performed with fresh and frozen urine and the culture transport medium.
      LCR was performed with fresh and frozen urine and LCx swab transport medium.
      Diagnostic consistency and diagnostic accuracy were statistically tested. The
      test results were identical for 984 patients (97%). Discrepant results were
      observed for 31 patients. Overall, LCR and PCR showed excellent kappa
      coefficients of consistency for both swab and FVU specimens (0.93 and 0.95,
      respectively). Sixty-one patients (6%) were culture positive. Testing of FVU by
      LCR or PCR increased the overall positivity rates to 7.0 and 7.7%, respectively.
      While PCR of FVU detected the greatest number of C. trachomatis infections
      (sensitivity, 96.1%), for some PCR-positive FVU specimens the results could not
      be confirmed (specificity, 99.6%). PCR and LCR were more sensitive than culture
      (sensitivities, 92 and 93% versus 79% for culture) in the diagnosis of genital C.
      trachomatis infection. In conclusion, both tests can be recommended for use in
      the clinical laboratory and for the screening of asymptomatic C. trachomatis
      infections.

PMID- 9620367
TI  - Molecular typing of environmental and patient isolates of Aspergillus fumigatus
      from various hospital settings.
AB  - Fingerprinting of more than 700 clinical and environmental isolates of
      Aspergillus fumigatus from four differential hospital settings was undertaken
      with a dispersed repeated DNA sequence. The analysis of the environmental
      isolates showed that the airborne A. fumigatus population is extremely diverse,
      with 85% of the strains being represented as a single genotype isolated once. The
      remaining 15% of the strains were isolated several times and were able to persist
      for several months in the same hospital environment. No strains were found to be
      associated with a specific location inside the hospital, and identical strains
      were isolated from different buildings of the hospital and outdoors. Isolation of
      the same strain both from patients and from the environment of the same hospital
      is highly suggestive of a nosocomial infection. The characteristics of the
      environmental fungal population explains the two main results obtained from the
      typing of the clinical isolates: (i) the absence of a common strain responsible
      for an invasive aspergillosis outbreak results from the extreme diversity of the
      environmental population of A. fumigatus in contact with the patients, and (ii)
      patients hospitalized in different wards of the same hospital can be infected
      with the same strain since every patient might inhale the same spore population.

PMID- 9620368
TI  - Production and characterization of Ehrlichia risticii, the agent of Potomac horse
      fever, from snails (Pleuroceridae: Juga spp.) in aquarium culture and genetic
      comparison to equine strains.
AB  - We report on the production and characterization of Ehrlichia risticii, the agent
      of Potomac horse fever (PHF), from snails (Pleuroceridae: Juga spp.) maintained
      in aquarium culture and compare it genetically to equine strains. Snails were
      collected from stream waters on a pasture in Siskiyou County, Calif., where PHF
      is enzootic and were maintained for several weeks in freshwater aquaria in the
      laboratory. Upon exposure to temperatures above 22 degrees C the snails released
      trematode cercariae tentatively identified as virgulate cercariae. Fragments of
      three different genes (genes for 16S rRNA, the groESL heat shock operon, and the
      51-kDa major antigen) were amplified from cercaria lysates by PCR and sequenced.
      Genetic information was also obtained from E. risticii strains from horses with
      PHF. The PCR positivity of snail secretions was associated with the presence of
      trematode cercariae. Sequence analysis of the three genes indicated that the
      source organism closely resembled E. risticii, and the sequences of all three
      genes were virtually identical to those of the genes of an equine E. risticii
      strain from a property near the snail collection site. Phylogenetic analyses of
      the three genes indicated the presence of geographical E. risticii strain
      clusters.

PMID- 9620369
TI  - Evaluation of PCR in detection of Mycobacterium tuberculosis from formalin-fixed,
      paraffin-embedded tissues: comparison of four amplification assays.
AB  - We compared the sensitivities and specificities of four nested PCR assays for the
      detection of Mycobacterium tuberculosis from formalin-fixed, paraffin-embedded
      tissues. Thirty-seven autopsy samples from human immunodeficiency virus-positive
      patients were analyzed: 15 were M. tuberculosis positive, 11 served as negative
      controls, and 11 were Ziehl-Neelsen positive without cultural confirmation of M.
      tuberculosis. Three genomic sequences (mtp40, 65-kDa antigen gene, and IS6110)
      with different molecular masses and numbers of repetitions within the M.
      tuberculosis genome were targeted. On the IS6110 sequence, two fragments of
      different sizes (106 and 123 bp, respectively) were amplified with two separate
      pairs of primers. The highest sensitivity rates were obtained by amplifying the
      highly repetitive IS6110 insertion sequence, and the different primers tested
      showed a sensitivity ranging from 80 to 87%. Amplification of the large 223-bp
      fragment of the mtp40 sequence present in a single copy in the M. tuberculosis
      genome yielded a high rate of false-negative results, ranging from 66 to 80%. A
      poor sensitivity (from 47 to 60%) was also shown by PCR amplification of the 142
      bp 65-kDa antigen gene. All the PCRs except that for the 65-kDa antigen gene
      showed a specificity of 100%. Moreover, different results were obtained with
      different dilutions of DNA, and DNA concentrations of 1 and 3 microg yielded the
      highest sensitivities depending upon which protocol was used. Application of the
      PCRs to the Ziehl-Neelsen-positive, culture-negative samples confirmed the
      sensitivities of the PCRs obtained with the control samples. In conclusion, PCR
      can successfully be used to detect M. tuberculosis from paraffin-embedded tissues
      and can be particularly useful in the validation of a diagnosis of tuberculosis
      in clinical settings in which the diagnosis is uncertain. However, the efficacy
      of PCR strictly depends on several amplification parameters such as DNA
      concentration, target DNA size, and the repetitiveness of the amplified sequence.

PMID- 9620370
TI  - Hospital specificity, region specificity, and fluconazole resistance of Candida
      albicans bloodstream isolates.
AB  - In a survey of bloodstream infection (BSI) isolates across the continental United
      States, 162 Candida albicans isolates were fingerprinted with the species
      specific probe Ca3 and the patterns were analyzed for relatedness with a computer
      assisted system. The results demonstrate that particular BSI strains are more
      highly concentrated in particular geographic locales and that established BSI
      strains are endemic in some, but not all, hospitals in the study and undergo
      microevolution in hospital settings. The results, however, indicate no close
      genetic relationship among fluconazole-resistant BSI isolates in the collection,
      either from the same geographic locale or the same hospital. This study
      represents the first of three fingerprinting studies designed to analyze the
      origin, genetic relatedness, and drug resistance of Candida isolates responsible
      for BSI.

PMID- 9620371
TI  - Routine use of PCR-reverse cross-blot hybridization assay for rapid
      identification of Mycobacterium species growing in liquid media.
AB  - A PCR-reverse cross-blot hybridization assay procedure that is able to rapidly
      identify 13 species of clinically relevant mycobacteria was evaluated for routine
      use in the identification of acid-fast isolates growing in BACTEC 460 TB (12B and
      13A) and BACTEC 9000 MB (Myco/F) liquid media. Eight of the probes used were
      already described by Kox et al. (L. F. F. Kox et al., J. Clin. Microbiol. 33:3225
      3233, 1995). In addition, we used six other probes specific for M. chelonae, M.
      malmoense or M. szulgai, M. genavense, M. gordonae, M. terrae, and M. marinum/M.
      ulcerans that we designed ourselves. This procedure allowed us to identify 459
      mycobacterial species directly from broth cultures of 5,466 clinical samples
      collected over 1 year and processed with the radiometric or nonradiometric BACTEC
      system. Our results were in agreement with those obtained by conventional
      identification methods and also with those obtained by mycolic acid analysis by
      high-performance liquid chromatography. This assay seems to be a reliable
      procedure for the routine identification of mycobacteria, providing an accurate
      identification of mycobacterial isolates more rapidly than conventional tests,
      with remarkable implications for an efficacious specific antimycobacterial
      therapy.

PMID- 9620372
TI  - Detection of human immunodeficiency virus type 1 (HIV-1) RNA in pools of sera
      negative for antibodies to HIV-1 and HIV-2.
AB  - A total of 234 pools were prepared from 10,692 consecutive serum samples negative
      for antibodies to human immunodeficiency virus type 1 (HIV-1) and HIV-2 collected
      at five virological laboratories (average pool size, 45 serum samples). Pools
      were screened for the presence of HIV-1 RNA by a modified commercial assay
      (Amplicor HIV-1 Monitor test) which included an additional polyethylene glycol
      (PEG) precipitation step prior to purification of viral RNA (PEG Amplicor assay).
      The sensitivity of this assay for HIV-1 RNA detection in individual serum samples
      within pools matches that of standard commercial assays for individual serum
      samples, i.e., 500 HIV-1 RNA copies per ml. Five pools were identified as
      positive, and each one contained one antibody-negative, HIV-1 RNA-positive serum
      sample, corresponding to an average of 1 infected sample per 2,138 serum samples.
      Retrospective analysis revealed that the five HIV-1 RNA-positive specimens
      originated from individuals who had symptomatic primary HIV-1 infection at the
      time of sample collection and who were also positive for p24 antigenemia. We next
      assessed the possibility of performing the prepurification step by high-speed
      centrifugation (50,000 x g for 80 min) of 1.5-ml pools containing 25 microl of 60
      individual serum samples, of which only 1 contained HIV-1 RNA (centrifugation
      Amplicor assay). The sensitivity of this assay also matches the sensitivities of
      standard commercial assays for HIV-1 RNA detection in individual serum samples.
      The results demonstrate that both assays with pooled sera can be applied to the
      screening of large numbers of serum samples in a time- and cost-efficient manner.

PMID- 9620373
TI  - Characteristics of Arthrobacter cumminsii, the most frequently encountered
      Arthrobacter species in human clinical specimens.
AB  - During a 2-year period, 10 strains of Arthrobacter cumminsii were isolated in or
      received by a Swiss routine clinical bacteriology laboratory, and 5 further
      isolates were referred to a Swedish bacteriology reference center over a 5-year
      period, making A. cumminsii the most frequently encountered Arthrobacter species
      in these two laboratories. The present report outlines the clinical features of
      the 15 A. cumminsii strains and presents an extended biochemical characterization
      of this microorganism. A. cumminsii exhibits a unique cellular fatty acid pattern
      with the consistent presence of C14:0i and C14:0 fatty acids as well as
      relatively large amounts of C16:0i and C16:0 fatty acids usually not seen in
      other Arthrobacter spp. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      was found to be a useful tool for confirmation of the identification of A.
      cumminsii. The MICs of 39 antimicrobial agents were determined, and it was
      demonstrated that aminoglycosides and quinolones had only weak activities against
      A. cumminsii strains, in contrast to their activities against most other
      coryneform bacteria. As a result of the extended characterization of A.
      cumminsii, an emended description of this species is presented. Due to the lack
      of A. cumminsii in established identification systems, it is most likely that
      this species is underdiagnosed in many routine clinical bacteriology
      laboratories.

PMID- 9620374
TI  - Identification of new influenza B virus variants by multiplex reverse
      transcription-PCR and the heteroduplex mobility assay.
AB  - A quick genetic approach for the screening of influenza virus variants was
      developed in this laboratory (S. Zou, J. Clin. Microbiol. 35:2623-2627, 1997). It
      uses multiplex reverse transcription and multiplex PCR to amplify and
      differentiate the variable region of the hemagglutinin genes of different types
      and subtypes of influenza viruses. Variants within the same type or subtype are
      then identified by the heteroduplex mobility shift assay of the amplicons. The
      method was used to screen influenza virus isolates received from provincial
      laboratories during the 1996-1997 season and was able to identify new influenza B
      virus variants. Sequencing of the amplicons derived from the hemagglutinin gene
      of the identified variants and comparison with the vaccine strain B/Harbin/7/94
      showed substitution rates of 2.26 to 2.55% at the nucleotide level and 4.26 to
      4.68% at the amino acid level. The result further demonstrated that the approach
      provides a quick, sensitive, and reliable screening for influenza virus variants.
      It also suggested the necessity of close monitoring of influenza B virus isolates
      in the 1997-1998 season and critical evaluation of the reference strain for the
      type B influenza virus.

PMID- 9620375
TI  - Suitability of repetitive-DNA-sequence-based PCR fingerprinting for
      characterizing epidemic isolates of Salmonella enterica serovar Saintpaul.
AB  - Three molecular typing methods, repetitive-sequence-based PCR (rep-PCR)
      fingerprinting, plasmid profiling, and arbitrarily primed PCR fingerprinting,
      were used to characterize isolates of Salmonella enterica serovar Saintpaul. Most
      of the isolates were obtained from epidemic human cases of food-borne
      salmonellosis, together with some from the food material suspected to be the
      source of infection, and a few were obtained from other cases apparently not
      related to the epidemic. All three methods adequately discriminated the epidemic
      strain from other strains of the serovar. In addition several isolates from human
      cases which are not identical to the epidemic strain were found. These isolates
      therefore must have been responsible for some sporadic infections, which were
      only temporally related to the epidemic. These strains showed a high degree of
      similarity to a strain isolated from a turkey. rep-PCR fingerprinting with REP-Dt
      primers and primer ERIC1R, applicable even to crude cell lysates, offers an
      attractive choice as a primary method for the discrimination of various
      Salmonella serotypes as well as isolates within serotype Saintpaul.

PMID- 9620376
TI  - Variables affecting results of sodium chloride tolerance test for identification
      of rapidly growing mycobacteria.
AB  - The sodium chloride tolerance test is often used in the identification of rapidly
      growing mycobacteria, particularly for distinguishing between Mycobacterium
      abscessus and Mycobacterium chelonae. This test, however, is frequently
      unreliable for the identification of some species. In this study we examined the
      following variables: medium manufacturer, inoculum concentration, and atmosphere
      and temperature of incubation. Results show that reliability is improved if the
      test and control slants are inoculated with an organism suspension
      spectrophotometrically equal to a 1 McFarland standard. Slants should be
      incubated at 35 degrees C in ambient air and checked weekly for 4 weeks. Growth
      on control slants should be critically evaluated to determine the adequacy of the
      inoculum; colonies should number greater than 50. Salt-containing media should be
      examined carefully to detect pinpoint or tiny colonies, and colonies should
      number greater than 50 for a positive reaction. Concurrent use of a citrate slant
      may be helpful for distinguishing between M. abscessus and M. chelonae. Molecular
      methodologies are probably the most reliable means for the identification of
      rapidly growing mycobacteria and should be used, if possible, when unequivocal
      species identification is of particular importance.

PMID- 9620378
TI  - Flow cytometric testing of susceptibilities of Mycobacterium tuberculosis
      isolates to ethambutol, isoniazid, and rifampin in 24 hours.
AB  - Susceptibility testing of Mycobacterium tuberculosis is seriously limited by the
      time required to obtain results. We show that susceptibility testing of clinical
      isolates of M. tuberculosis can be accomplished rapidly with acceptable accuracy
      by using flow cytometry. The susceptibilities of 35 clinical isolates of M.
      tuberculosis to various concentrations of isoniazid, rifampin, and ethambutol
      were tested by the agar proportion method and by flow cytometry. Agreement
      between the results from the two methods was 95, 92, and 83% for isoniazid,
      ethambutol, and rifampin, respectively. Only 11 discrepancies were detected among
      155 total tests. The results of flow cytometric susceptibility tests were
      available within 24 h of inoculation of drug-containing medium, while the
      proportion method required 3 weeks to complete. The flow cytometric method is
      also simple to perform.

PMID- 9620377
TI  - Sequence-based classification scheme for the genus Legionella targeting the mip
      gene.
AB  - The identification and speciation of strains of Legionella is often difficult,
      and even the more successful chromatographic classification techniques have
      struggled to discriminate newly described species. A sequence-based genotypic
      classification scheme is reported, targeting approximately 700 nucleotide bases
      of the mip gene and utilizing gene amplification and direct amplicon sequencing.
      With the exception of Legionella geestiana, for which an amplicon was not
      produced, the scheme clearly and unambiguously discriminated among the remaining
      39 Legionella species and correctly grouped 26 additional serogroup and reference
      strains within those species. Additionally, the genotypic classification of
      approximately 150 wild strains from several continents was consistent with their
      phenotypic classification, with the exception of a few strains where serological
      cross-reactivity was complex, potentially confusing the latter classification.
      Strains thought to represent currently uncharacterized species were also found to
      be genotypically unique. The scheme is technically simple for a laboratory with
      even basic molecular capabilities and equipment, if access to a sequencing
      laboratory is available.

PMID- 9620379
TI  - Mapping and serodiagnostic application of a dominant epitope within the human
      herpesvirus 8 ORF 65-encoded protein.
AB  - A dominant epitope within the human herpesvirus 8 (HHV8) ORF 65-encoded protein
      was mapped to an 8-amino-acid (aa) sequence (RKPPSGKK [aa 162 to 169]) by an
      amino acid replacement method. Using a 14-aa peptide (P4) encompassing this
      epitope as the antigen, we developed an enzyme immunoassay for HHV8 antibodies.
      The presence of P4 antibodies in a panel of 61 human serum specimens was highly
      correlated with biopsy-confirmed Kaposi's sarcoma. The homologous Epstein-Barr
      virus peptide derived from BFBR3-encoded protein did not interfere with the
      assay, suggesting that P4 is specific for HHV8.

PMID- 9620380
TI  - Comparison of three methods for testing azole susceptibilities of Candida
      albicans strains isolated sequentially from oral cavities of AIDS patients.
AB  - Three susceptibility testing procedures were compared to determine fluconazole,
      itraconazole, and ketoconazole MICs against 47 Candida albicans strains isolated
      sequentially from the oral cavities of five AIDS patients undergoing azole
      therapy. They included the broth microdilution method (BM), performed according
      to the National Committee for Clinical Laboratory Standards' tentative standard,
      the agar dilution method (AD), and the Etest; the latter two tests were performed
      both in Casitone agar (AD-Cas and Etest-Cas) and in RPMI (AD-RPMI and Etest
      RPMI). Twenty-four- and 48-h MICs obtained by AD and Etest were compared with 48
      h MICs obtained by BM. The MICs of all the azoles determined by BM were usually
      lower than those obtained by the other methods, mainly due to different reading
      criteria. In order to assess the most appropriate way of evaluating the agreement
      of MICs obtained by different methods with those produced by the proposed
      reference method (BM), we used the mean differences calculated according to Bland
      and Altman's method. Comparison of fluconazole MICs obtained by BM and AD-Cas
      yielded a mean difference of 3, and the percentages of agreement within +/-2
      dilutions were 98 and 100% at 24 and 48 h, respectively. For ketoconazole and
      itraconazole MICs, lower mean differences were noted, and agreement ranged from
      96 to 100%. Agreement between the AD-RPMI and BM results was poor for all azoles,
      and an increase in MICs was always observed between the 1st- and 2nd-day
      readings. Similarly, Etest-Cas gave better agreement with BM than did Etest-RPMI
      for all the azoles. BM, AD-Cas, and Etest-Cas each demonstrated a progressive
      increase in fluconazole MICs against strains isolated sequentially from a given
      patient, in accordance with the decreased clinical response to fluconazole.

PMID- 9620381
TI  - Use of tests for acidification of methyl-alpha-D-glucopyranoside and
      susceptibility to efrotomycin for differentiation of strains of Enterococcus and
      some related genera.
AB  - A total of 107 Enterococcus strains, 10 Vagococcus fluvialis strains, and 8
      Lactococcus garvieae strains were tested for acidification of methyl-alpha-D
      glucopyranoside (MGP) and susceptibility to 100-microg efrotomycin (EFRO) disks.
      All 26 strains of Enterococcus casseliflavus, including 3 nonmotile and 2
      nonpigmented strains, acidified MGP and were resistant to EFRO. All 22 strains of
      Enterococcus gallinarum, including 5 nonmotile strains, also acidified MGP and
      were resistant to EFRO. None of the 26 strains of Enterococcus faecium acidified
      MGP, and all were susceptible to EFRO. Although all 12 Enterococcus faecalis
      strains were also negative in the MGP test, they were resistant to EFRO. Other
      enterococcal strains gave variable results. All 10 strains of V. fluvialis and
      all 8 strains of L. garvieae gave positive and negative results, respectively, in
      the MGP test and were, respectively, resistant and susceptible to EFRO. These
      results indicate that tests of the production of acid from MGP and susceptibility
      to EFRO can be used as adjunct tests in the identification of typical and
      atypical strains of enterococci in the clinical microbiology laboratory.

PMID- 9620382
TI  - Differentiation and characterization of enteroviruses by computer-assisted viral
      protein fingerprinting.
AB  - We have developed and standardized a computerized method for the typing and
      characterization of enteroviruses with radiolabeled viral protein fingerprints.
      Enteroviral proteins were radiolabeled with [35S]methionine during growth in cell
      culture and were then separated by polyacrylamide gel electrophoresis. The dried
      gel was scanned, and from the resulting computer image (which resembled an
      autoradiogram) protein patterns were computer extracted and stored in a database.
      The enterovirus database contained community and prototype strains belonging to
      20 different enteroviral serotypes. Each serotype has a discrete protein pattern,
      and the most important pattern differences for determining each type are in the
      region of the viral capsid proteins VP1, VP2, and VP3. When the database was
      challenged with 148 clinical enterovirus strains, 144 (97%) were correctly
      identified by using the correlation coefficient as a quantitative measure of
      relatedness between two patterns. This method can identify a type in a single
      test and represents a practical alternative to virus neutralization because it is
      less expensive, is much faster (3 rather than 10 days), and does not rely on any
      virus-specific reagents. The results also show that most of the strains currently
      isolated from the community have protein patterns different from those of their
      older prototype strains. Viral protein fingerprinting is an evolving, dynamic
      system for the typing and characterization of enteroviruses. The method is
      appropriate for use in clinical virology and reference laboratories for the
      typing of enteroviruses, for the study of the epidemiology of enteroviruses, and
      for surveillance of enteroviruses.

PMID- 9620383
TI  - Molecular analysis of and identification of antibiotic resistance genes in
      clinical isolates of Salmonella typhi from India.
AB  - A representative sample of 21 Salmonella typhi strains isolated from cultures of
      blood from patients at the Christian Medical College and Hospital, Vellore,
      India, were tested for their susceptibilities to various antimicrobial agents.
      Eleven of the S. typhi strains possessed resistance to chloramphenicol (256
      mg/liter), trimethoprim (64 mg/liter), and amoxicillin (>128 mg/liter), while
      four of the isolates were resistant to each of these agents except for
      amoxicillin. Six of the isolates were completely sensitive to all of the
      antimicrobial agents tested. All the S. typhi isolates were susceptible to
      cephalosporin agents, gentamicin, amoxicillin plus clavulanic acid, and imipenem.
      The antibiotic resistance determinants in each S. typhi isolate were encoded by
      one of four plasmid types. Plasmid-mediated antibiotic resistance genes were
      identified with specific probes in hybridization experiments; the genes
      responsible for chloramphenicol, trimethoprim, and ampicillin resistance were
      chloramphenicol acetyltransferase type I, dihydrofolate reductase type VII, and
      TEM-1 beta-lactamase, respectively. Pulsed-field gel electrophoresis analysis of
      XbaI-generated genomic restriction fragments identified a single distinct profile
      (18 DNA fragments) for all of the resistant isolates. In comparison, six
      profiles, different from each other and from the resistance profile, were
      recognized among the sensitive isolates. It appears that a single strain
      containing a plasmid conferring multidrug-resistance has emerged within the S.
      typhi bacterial population in Vellore and has been able to adapt to and survive
      the challenge of antibiotics as they are introduced into clinical medicine.

PMID- 9620384
TI  - Multicenter comparison of BACTEC 9050 and BACTEC 9240 blood culture systems.
AB  - The overall recovery of organisms and time to detection with the BACTEC 9050 and
      BACTEC 9240 systems were compared in a multicenter evaluation. In the first phase
      of the study, a total of 4,383 compliant aerobic (Plus Aerobic/F) blood culture
      sets were processed. There was no significant difference in the recovery of
      individual groups of organisms with the two systems, with the exception of
      Streptococcus pneumoniae which was isolated more frequently with BACTEC 9050.
      False-positive signals occurred more often with BACTEC 9240 (58 cultures) than
      with BACTEC 9050 (43 cultures), but false-negative cultures were uncommon with
      both systems (3 cultures for each system). Time to detection of positive cultures
      of clinically significant organisms was essentially the same with both
      instruments. In the second phase of the study, 2,431 compliant anaerobic (Plus
      Anaerobic/F) blood culture sets were processed. There was no significant
      difference in the recovery of organisms with BACTEC 9050 compared with BACTEC
      9240. Significantly (P < 0.03) more false-positive signals occurred with BACTEC
      9240 (15 cultures) than with BACTEC 9050 (4 cultures). Likewise, more false
      negative cultures occurred with BACTEC 9240 (11 cultures) than with BACTEC 9050
      (8 cultures). Time to detection of positive cultures of clinically significant
      organisms was essentially the same with both systems with the exception of
      anaerobes (N = 10), which were recovered earlier (P < 0.01) with BACTEC 9240
      (35.0 h) than with BACTEC 9050 (61.4 h).

PMID- 9620385
TI  - Virulence properties of Shiga toxin-producing Escherichia coli (STEC) strains of
      serogroup O118, a major group of STEC pathogens in calves.
AB  - Shiga toxin-producing Escherichia coli (STEC) strains of serogroup 0118 are the
      most prevalent group among STEC strains in diarrheic calves in Germany (L. H.
      Wieler, Ph.D. thesis, University of Giessen, 1997). To define their virulence
      properties, 42 0118 (0118:H16 [n = 38] and 0118:H- [n = 4]) strains were
      characterized. The strains displayed three different Stx combinations (Stx1 [36
      of 42], Stx1 and Stx2 [2 of 42], and Stx2 [4 of 42]). A total of 41 strains
      (97.6%) harbored a large virulence-associated plasmid containing hlyEHEC (hly
      from enterohemorrhagic E. coli). The strains' adhesive properties varied in
      relation to the eukaryotic cells tested. Only 28 of 42 strains (66.7%) showed
      localized adhesion (LA) in the human HEp-2 cell line. In contrast, in bovine
      fetal calf lung (FCL) cells, the number of LA-positive strains was much higher
      (37 of 42 [88.1%]). The locus of enterocyte effacement (LEE) was detected in 41
      strains (97.6%). However, not all LEE-positive strains reacted positively in the
      fluorescence actin-staining (FAS) test, which indicated the attaching and
      effacing (AE) lesion. In HEp-2 cells, only 22 strains (52.4%) were FAS positive,
      while in FCL cells, the number of FAS-positive strains was significantly higher
      (38 of 42 [90.5%; P < 0.001]). In conclusion, the vast majority of the 0118 STEC
      strains from calves (41 of 42 [97.6%]) have a high virulence potential (stx,
      hlyEHEC, and LEE). This virulence potential and the high prevalence of STEC 0118
      strains in calves suggest that these strains could be a major health threat for
      humans in the future. In addition, the poor association between results of the
      geno- and phenotypical tests to screen for the AE ability of STEC strains calls
      the diagnostic value of the FAS test into question.

PMID- 9620387
TI  - Detection of antigen in sera of patients with invasive aspergillosis: intra- and
      interlaboratory reproducibility. The Dutch Interuniversity Working Party for
      Invasive Mycoses.
AB  - The intra- and interlaboratory reproducibilities of a commercial sandwich enzyme
      linked immunosorbent assay (ELISA) for the detection of Aspergillus galactomannan
      in serum (Platelia Aspergillus; Sanofi Diagnostics Pasteur, Marnes-La-Coquette,
      France) were evaluated in six laboratories of university hospitals. Twenty serum
      samples were obtained from 12 neutropenic patients including 6 with invasive
      aspergillosis. These samples were blinded and sent to each center together with
      eight blinded ELISA-negative serum samples spiked with known concentrations of
      galactomannan. The centers were provided with ELISA microtiter plates from a
      single batch and a detailed protocol. Ten clinical samples showed ELISA
      reactivity, while 10 samples were ELISA negative. The mean coefficient of
      variation (CV) of the optical density values was 4.24% within a single assay and
      25.6% between runs. The interassay CV of the ratios for the serum samples tested
      was 18.6%. Analysis of ordinal interpretation of the ELISA result (i.e.,
      negative, gray zone, or positive) showed excellent reproducibility. Recalculation
      of the cutoff values for positive and negative samples suggested that the cutoff
      level recommended by the manufacturer could be lowered from 1.0 to 0.8 for
      negative samples and from 1.5 to 1.0 for positive samples. The intra- and
      interlaboratory reproducibilities were excellent when the ELISA results were
      interpreted as ordinal data, but considerable variation in optical density values
      and, to a lesser extent, in the ratios for the serum samples tested, was observed
      between runs. High assay variability was also found for serum samples spiked with
      known concentrations of galactomannan. Therefore, antigen titers in serum samples
      from a single patient, measured in different runs, should be compared with
      caution.

PMID- 9620386
TI  - Sensitivities and specificities of premier E. coli O157 and premier EHEC enzyme
      immunoassays for diagnosis of infection with verotxin (Shiga-like toxin)
      producing Escherichia coli. The SYNSORB Pk Study investigators.
AB  - This study describes the performance of two rapid enzyme immunoassays, Premier E.
      coli O157 and Premier EHEC (Meridian Diagnostics Inc., Cincinnati, Ohio) for the
      detection in stools of Escherichia coli O157 and verotoxins (Shiga-like toxins),
      respectively. Both tests were performed on stools from 876 children presenting to
      eight emergency departments with diarrhea. Standard culture, including E. coli
      O157:H7 isolation, was performed, and paired sera were taken for anti-O157
      lipopolysaccharide antibody determination. Stools from patients enrolled in the
      study, and those yielding discordant results, were sent to a reference laboratory
      for repeat testing and further investigation, including cytotoxicity and non-O157
      verotoxin-producing E. coli culture. Results were classified as field results
      (obtained in the eight site laboratories) and resolved results (obtained after
      repeat testing in the central laboratory). The "gold standard" for sensitivity of
      both tests and for specificity of Premier E. coli O157 was isolation of E. coli
      O157:H7 or a fourfold anti-O157 antibody rise. Specimens positive by the Premier
      EHEC test and negative for E. coli O157 culture were examined for non-O157
      verotoxin-producing E. coli. The field sensitivity of Premier E. coli O157 was
      86%, that of Premier EHEC was 89%, and the specificity of Premier E. coli O157
      was 98%. Ten of 13 discordant Premier E. coli O157 results were reassigned as
      true results after repeat testing. Ten non-O157 verotoxin-producing E. coli
      isolates were recovered from Premier EHEC-positive, E. coli O157 culture-negative
      stools. Only one specimen gave an unequivocally false-positive Premier EHEC
      result. Both tests are highly sensitive and are specific if correctly performed.
      The Premier EHEC test will be particularly valuable as a practical routine test
      for the detection of non-O157 verotoxin-producing E. coli.

PMID- 9620388
TI  - Microscopic examination and broth culture of cerebrospinal fluid in diagnosis of
      meningitis.
AB  - We reviewed the results of microscopic Gram stain examination and routine culture
      for 2,635 cerebrospinal fluid (CSF) samples processed in an adult hospital
      microbiology laboratory during 55 months. There were 56 instances of bacterial or
      fungal meningitis (16 associated with central nervous system [CNS] shunt
      infection), four infections adjacent to the subarachnoid space, four cases of
      sepsis without meningitis, and an additional 220 CSF specimens with positive
      cultures in which the organism isolated was judged to be a contaminant. Because
      121 of these contaminants were isolated in broth only, elimination of the broth
      culture would decrease unnecessary work. However, 25% of the meningitis
      associated with CNS shunts would have been missed by this practice. The most
      common cause of meningitis was Cryptococcus neoformans, followed by Streptococcus
      pneumoniae and Neisseria meningitidis. In 48 of 56 (88%) of cases, examination of
      the Gram-stained specimen revealed the causative organism. If patients who had
      received effective antimicrobial therapy prior to lumbar puncture are excluded,
      the CSF Gram stain is 92% sensitive. Microscopic examination incorrectly
      suggested the presence of organisms in only 3 of 2,635 (0.1%) CSF examinations.
      Thus, microscopic examination of Gram-stained, concentrated CSF is highly
      sensitive and specific in early diagnosis of bacterial or fungal meningitis.

PMID- 9620389
TI  - Use of PCR for diagnosis of post-kala-azar dermal leishmaniasis.
AB  - Microscopy and PCR were compared for use in the diagnosis of post-kala-azar
      dermal leishmaniasis (PKDL) in 63 patients. Aspirates of lymph nodes (samples
      from 52 patients), skin (23 samples), and bone marrow (18 samples) were used. For
      11 patients lymph node aspiration could be repeated 6 months after they recovered
      from PKDL. During active PKDL, PCR was positive for 42 of 52 (80.8%) lymph node
      aspirates and 19 of 23 (82.7%) skin aspirates, whereas microscopy was positive
      for only 9 of 52 (17.3%) lymph node aspirates and 7 of 23 (30.4%) skin aspirates.
      PCR was always positive when parasites were seen by microscopy. When the results
      obtained with lymph node and skin aspirates from the same patient (n = 16) were
      compared, there was complete agreement. Bone marrow samples were negative by
      microscopy and PCR for 16 patients and positive by both methods for 1 patient;
      for one sample only the PCR was positive. PCR confirmed the co-occurrence of
      visceral leishmaniasis and PKDL in one patient and confirmed the suspicion of
      this co-occurrence in the other patient. After recovery, no parasites were found
      by microscopy, but 2 of 11 (18.2%) samples were still positive by PCR. Thirty
      negative controls were all found to be PCR negative, and 15 positive controls
      were all PCR positive. Cross-reactions with Mycobacterium leprae could be ruled
      out. In conclusion, PCR with inguinal lymph node or skin aspirates is suitable
      for confirming the clinical diagnosis of PKDL. In some patients, lymph node
      aspirates are probably preferred because aspiration of material from the skin may
      leave scars.

PMID- 9620390
TI  - Rapid extraction of genomic DNA from medically important yeasts and filamentous
      fungi by high-speed cell disruption.
AB  - Current methods of DNA extraction from different fungal pathogens are often time
      consuming and require the use of toxic chemicals. DNA isolation from some fungal
      organisms is difficult due to cell walls or capsules that are not readily
      susceptible to lysis. We therefore investigated a new and rapid DNA isolation
      method using high-speed cell disruption (HSCD) incorporating chaotropic reagents
      and lysing matrices in comparison to standard phenol-chloroform (PC) extraction
      protocols for isolation of DNA from three medically important yeasts (Candida
      albicans, Cryptococcus neoformans, and Trichosporon beigelii) and two filamentous
      fungi (Aspergillus fumigatus and Fusarium solani). Additional extractions by HSCD
      were performed on Saccharomyces cerevisiae, Pseudallescheria boydii, and Rhizopus
      arrhizus. Two different inocula (10(8) and 10(7) CFU) were compared for
      optimization of obtained yields. The entire extraction procedure was performed on
      as many as 12 samples within 1 h compared to 6 h for PC extraction. In comparison
      to the PC procedure, HSCD DNA extraction demonstrated significantly greater
      yields for 10(8) CFU of C. albicans, T. beigelii, A. fumigatus, and F. solani (P
      < or = 0.005), 10(7) CFU of C. neoformans (P < or = 0.05), and 10(7) CFU of A.
      fumigatus (P < or = 0.01). Yields were within the same range for 10(8) CFU of C.
      neoformans and l0(7) CFU of C. albicans for both HSCD extraction and PC
      extraction. For 10(7) CFU of T. beigelii, PC extraction resulted in a greater
      yield than did HSCD (P < or = 0.05). Yields obtained from 10(8) and 10(7) CFU
      were significantly greater for filamentous fungi than for yeasts by the HSCD
      extraction procedure (P < 0.0001). By the PC extraction procedure, differences
      were not significant. For all eight organisms, the rapid extraction procedure
      resulted in good yield, integrity, and quality of DNA as demonstrated by
      restriction fragment length polymorphism, PCR, and random amplified polymorphic
      DNA. We conclude that mechanical disruption of fungal cells by HSCD is a safe,
      rapid, and efficient procedure for extracting genomic DNA from medically
      important yeasts and especially from filamentous fungi.

PMID- 9620391
TI  - Evaluation of the Abbott LCx ligase chain reaction assay for detection of
      Chlamydia trachomatis and Neisseria gonorrhoeae in urine and genital swab
      specimens from a sexually transmitted disease clinic population.
AB  - The Abbott LCx ligase chain reaction (LCR) assay for the simultaneous detection
      of Chlamydia trachomatis and Neisseria gonorrhoeae was evaluated by using swab
      and urine specimens from 562 patients. C. trachomatis results by LCR were
      compared to those by the Gen-Probe PACE 2 assay, whereas N. gonorrhoeae results
      by LCR were compared to those by culture. The Gen-Probe and LCR assays were
      performed according to the manufacturers' instructions. Gram-negative diplococci
      growing on modified Thayer-Martin medium were confirmed as N. gonorrhoeae by the
      GonoGen II assay. Supplemental data analysis was performed by major outer
      membrane protein PCR for C. trachomatis and probes for pilin gene detection for
      N. gonorrhoeae. A true-positive result for each pathogen was defined as a
      positive result for all three or two of three assays. Overall agreement among the
      six assays was 94.8%. C. trachomatis prevalence was 16.2%; N. gonorrhoeae
      prevalence was 5.5%. The overall sensitivity and specificity, respectively, for
      each test (after supplemental data analysis) were as follows: for C. trachomatis,
      Gen-Probe, 65.9 and 100%; LCR on urine, 90.1 and 100%; LCR on swab specimens,
      96.7 and 100%; and for N. gonorrhoeae, culture, 80.6 and 100%; LCR on urine, 93.5
      and 99.8%; and LCR on swab specimens, 96.8 and 100%. For women, the N.
      gonorrhoeae culture was very insensitive compared to its performance in men (58.3
      versus 94.7%, respectively). For C. trachomatis, the Gen-Probe assay's
      sensitivity was lower for men than for women (62.3 versus 71.1%, respectively).
      The sensitivity for C. trachomatis detection by LCR on urethral and cervical swab
      specimens was 96.2 and 97.4% for men and women, respectively. For men, swab
      results were slightly better than urine results for both pathogens (sensitivity
      for C. trachomatis in swab and urine specimens, 96.2 and 92.5%, respectively;
      sensitivity for N. gonorrhoeae in swab and urine specimens, 100 and 94.7%,
      respectively), while for women, cervical swabs were superior in sensitivity to
      urine samples for detecting C. trachomatis (swab, 97.4%; urine, 81.6%) and
      equivalent for N. gonorrhoeae (swab, 92.3%; urine, 91.6%). The LCx LCR appears to
      be both sensitive and specific for the detection of C. trachomatis and N.
      gonorrhoeae when performed on urine or genital swab samples. Swab samples had
      better sensitivity than urine samples for the detection of both pathogens.

PMID- 9620392
TI  - Rapid identification of Candida albicans and other human pathogenic yeasts by
      using short oligonucleotides in a PCR.
AB  - A PCR system that can quickly and accurately identify 14 species of human
      pathogenic yeasts was developed. The procedure distinguished between nine species
      of a closely related clade, Lodderomyces elongisporus, Candida parapsilosis, a
      new Candida sp., C. sojae, C. tropicalis, C. maltosa, C. viswanathii, C.
      albicans, and C. dubliniensis and between another five more divergent species,
      Pichia guilliermondii, C. glabrata, C. zeylanoides, C. haemulonii, and C.
      haemulonii type II. A rapid DNA extraction procedure that yields purified DNA in
      about 1 h is also described. The system uses uniform conditions with four primers
      for each reaction, two 40- to 50-mer universal primers that serve as a positive
      control and two 23- to 30-mer species-specific primers. Species-specific primers
      were derived from a 600-nucleotide variable region (D1/D2) at the 5' end of the
      large-subunit (26S) ribosomal DNA gene and were generally designed to use
      mismatches at the 3' end. Universal primers were developed from conserved
      nucleotide sequences in the small-subunit (18S) rRNA gene. In this system, a
      control 1,200- to 1,300-base DNA fragment was produced in all reactions and a
      smaller 114- to 336-base DNA fragment was produced if the chromosomal DNA from
      the target species was present. The PCR procedure is rapid and easy to interpret
      and may be used with mixed cultures.

PMID- 9620393
TI  - Comparison of culture and PCR for detection of Burkholderia cepacia in sputum
      samples of patients with cystic fibrosis.
AB  - We investigated the utility of PCR to detect Burkholderia cepacia directly in
      sputum samples at two cystic fibrosis (CF) centers serving children and adults.
      Following liquefaction of the sputa by using N-acetyl-L-cysteine, DNA was
      isolated and analyzed by PCRs with three different primer pairs directed toward
      bacterial rRNA loci. Two primer pairs were putatively specific for B. cepacia.
      The other pair, which universally amplifies a band from all bacteria, served as a
      control. Sputum samples were obtained from 219 patients and analyzed
      independently by culture and by PCR to detect B. cepacia. The analyses were
      performed blinded with respect to each other. The results of the PCR with sputa
      demonstrated that the primers directed to the 16S loci demonstrated approximately
      95% concordance with culture results and were more specific than those amplifying
      the 16S to 23S spacer region. In addition, the 16S primer pair putatively
      identified B. cepacia in seven patients whose sputa were culture negative at this
      time. Of these culture-negative patients, five had sputum samples that were
      culture positive for B. cepacia either prior or subsequent to this study. The
      results of this study indicate the utility of PCR as a diagnostic method for the
      rapid identification of B. cepacia in sputum samples of CF patients. We
      anticipate that improvements in our taxonomic understanding may allow the design
      of more specific primers for detection of each species of the B. cepacia complex
      in sputum samples.

PMID- 9620394
TI  - Diverse and related 16S rRNA-encoding DNA sequences in prostate tissues of men
      with chronic prostatitis.
AB  - Treatment of chronic prostatitis/chronic pelvic pain syndrome is often empirical
      because clinical culture methods fail to detect prostate-associated pathogens in
      >90% of patients. Previously, we tested a variety of specific-microorganism PCRs
      and began a DNA sequence study after we found that 77% of prostatitis patients
      were PCR positive for prokaryotic rRNA-encoding DNA sequences (rDNAs) despite
      negative cultures using optimal techniques. In the present study, 36 rDNA clones
      from 23 rDNA-positive patients were sequenced. This study represents more than
      twice the total rDNA sequence and more than twice the number of patients in the
      previous study. The increased number of patients and clones sequenced allowed
      enhanced phylogenetic analyses and refinements in our view of rDNA species
      inhabiting the prostate. A continuum of related rDNAs that might be arbitrarily
      described as two major groups of rDNAs and several minor groups was found.
      Sequences termed Pros A, identified in 8 (35%) of 23 rDNA-positive patients,
      grouped with Aeromonas spp. in phylogenetic studies. Sequences termed Pros B,
      identified in 17 (74%) of 23 rDNA-positive patients, were distinct from
      previously reported sequences, although all were >90% similar to known gram
      negative bacteria. Of the nine patients for whom multiple rDNAs were sequenced,
      six had biopsy specimens containing rDNAs from more than one species. Four (17%)
      patients had rDNAs different from those of the Pros A and Pros B groups. Of these
      four, one patient had rDNA similar to that of Flavobacterium spp., another had
      rDNA similar to that of Pseudomonas testosteroni, and two patients had rDNAs <70%
      similar to known rDNAs. These findings suggest that the prostate can harbor
      bacteria undetectable by traditional approaches. Most of these diverse sequences
      are not reported in environments outside the prostate. The sequence similarities
      suggest adaptation of limited groups of bacteria to the microenvironment of the
      prostate. Further studies may elucidate the relationship of prostate-associated
      bacteria to chronic prostatitis/chronic pelvic pain syndrome.

PMID- 9620395
TI  - Assessment of resolution and intercenter reproducibility of results of genotyping
      Staphylococcus aureus by pulsed-field gel electrophoresis of SmaI
      macrorestriction fragments: a multicenter study.
AB  - Twenty well-characterized isolates of methicillin-resistant Staphylococcus aureus
      were used to study the optimal resolution and interlaboratory reproducibility of
      pulsed-field gel electrophoresis (PFGE) of DNA macrorestriction fragments. Five
      identical isolates (one PFGE type), 5 isolates that produced related PFGE
      subtypes, and 10 isolates with unique PFGE patterns were analyzed blindly in 12
      different laboratories by in-house protocols. In several laboratories a
      standardized PFGE protocol with a commercial kit was applied successfully as
      well. Eight of the centers correctly identified the genetic homogeneity of the
      identical isolates by both the in-house and standard protocols. Four of 12
      laboratories failed to produce interpretable data by the standardized protocol,
      due to technical problems (primarily plug preparation). With the five related
      isolates, five of eight participants identified the same subtype
      interrelationships with both in-house and standard protocols. However, two
      participants identified multiple strain types in this group or classified some of
      the isolates as unrelated isolates rather than as subtypes. The remaining
      laboratory failed to distinguish differences between some of the related isolates
      by utilizing both the in-house and standardized protocols. There were large
      differences in the relative genome lengths of the isolates as calculated on the
      basis of the gel pictures. By visual inspection, the numbers of restriction
      fragments and overall banding pattern similarity in the three groups of isolates
      showed interlaboratory concordance, but centralized computer analysis of data
      from four laboratories yielded percent similarity values of only 85% for the
      group of identical isolates. The differences between the data sets obtained with
      in-house and standardized protocols could be the experimental parameters which
      differed with respect to the brand of equipment used, imaging software, running
      time (20 to 48 h), and pulsing conditions. In conclusion, it appears that the
      standardization of PFGE depends on controlling a variety of experimental
      intricacies, as is the case with other bacterial typing procedures.

PMID- 9620396
TI  - Tubulointerstitial nephritis due to a mutant polyomavirus BK virus strain,
      BKV(Cin), causing end-stage renal disease.
AB  - A renal biopsy from a 36-year-old man with AIDS showed a severe
      tubulointerstitial nephritis with intranuclear inclusions in epithelial cells.
      Electron microscopy revealed the characteristic findings of a polyomavirus (PyV)
      infection, and immunofluorescence indicated the presence of BK virus (BKV)
      antigen. Inoculation of rhesus monkey kidney cell cultures both with urine and
      with buffy coat blood cells resulted in a cytopathic response which was
      subsequently confirmed to be due to BKV. Further characterization of the viral
      DNA from the kidney by PCR amplification and Southern blot analysis with PyV and
      strain-specific primers and probes indicated that the virus was closely related
      to the BK(Dun) strain but different in its apparent sequence arrangement.
      Subsequent cycle sequencing showed a dinucleotide mutation of TG-->AA which
      substitutes hydrophilic Gln for hydrophobic Leu in a sequence homologous to an
      origin DNA-binding domain of simian virus 40 T antigen. It is suggested that the
      mutation and a coding region rearrangement of this strain of BKV designated
      BKV(Cin) has the potential to alter viral DNA replication and enhance
      pathogenicity.

PMID- 9620397
TI  - Cloning and expression of the 44-kilodalton major outer membrane protein gene of
      the human granulocytic ehrlichiosis agent and application of the recombinant
      protein to serodiagnosis.
AB  - A 44-kDa major outer membrane protein of the human granulocytic ehrlichiosis
      (HGE) agent is an immunodominant antigen in human infection. A gene encoding this
      protein was cloned and sequenced. Southern blot results revealed the existence of
      multigenes homologous to the P44 gene in the genome of the HGE agent. The
      recombinant 44-kDa protein (rP44) was expressed by using expression vector
      pET30a. The reactivity of the affinity-purified rP44 was evaluated by Western
      immunoblot analysis and dot blot immunoassay. Western immunoblot analysis showed
      that mouse anti-rP44 serum reacted with 44- to 42-kDa proteins in six different
      HGE agent strains tested except strain 2, in which three proteins of 42, 40, and
      38 kDa were recognized. Eleven HGE patient serum samples, a horse anti-HGE serum,
      and a horse anti-Ehrlichia equi serum recognized the rP44 protein. This suggests
      that rP44 is an HGE-E. equi group-specific antigen. Neither human anti-Ehrlichia
      chaffeensis serum nor rabbit anti-Borrelia burgdorferi serum reacted with rP44.
      Sera from two patients coinfected with the HGE agent and B. burgdorferi reacted
      positively with rP44 and the HGE agent. Sera from 20 HGE patients with indirect
      fluorescent-antibody (IFA) titers ranging from 1:20 to 1:2,560 gave distinct
      positive reactions in a dot immunoblot assay. There was a positive correlation
      between the color densities of the dot reactions and the IFA titers when greater
      than 50 ng of recombinant antigen per dot was used. The use of the affinity
      purified rP44 protein as antigen would provide a more specific, consistent, and
      simpler serodiagnosis for HGE than the use of whole infected cells or purified
      HGE agents.

PMID- 9620398
TI  - CDC group O-3: phenotypic characteristics, fatty acid composition, isoprenoid
      quinone content, and in vitro antimicrobic susceptibilities of an unusual gram
      negative bacterium isolated from clinical specimens.
AB  - Between 1983 and 1994, 13 phenotypically similar unidentified clinical isolates
      were received by the Special Bacteriology Reference Laboratory, Centers for
      Disease Control and Prevention (CDC). Sources included blood (four strains), lung
      (three strains), knee fluid and duodenal tissue (one strain each), bone, and
      lymph node tissue (two strains each). All were aerobic glucose-oxidizing,
      slender, long, curved gram-negative rods that utilized xylose, sucrose, and
      maltose; did not grow on MacConkey agar in 1 to 2 days; were oxidase positive;
      hydrolyzed esculin; and grew on Campylobacter selective medium. All were negative
      for urease, indole, nitrate reduction, and gelatin hydrolysis. All were motile by
      means of a single polar flagellum with a noticeably short wavelength; however,
      motility was sometimes difficult to demonstrate. The cellular fatty acid
      compositions of these strains, as analyzed by gas-liquid chromatography, were
      unique, characterized by relatively large amounts of 16:1omega7c, 16:0, and
      18:1omega7c with smaller amounts of 12:0, 3-OH-12:1, 14:0, 15:0, 18:0, Br-19:1,
      and 19:0cyc11-12. High-performance liquid chromatography and mass spectrometry of
      the quinone extracts of three representative strains showed ubiquinone-10 as the
      major component. Based on the breakpoints for the family Enterobacteriaceae, all
      the strains were susceptible in vitro to aminoglycosides, sulfamethoxazole
      trimethoprim, and chloramphenicol but were resistant to most beta-lactams except
      imipenem. The MICs of amoxicillin-clavulanate and ciprofloxacin for these strains
      clustered around the breakpoints, which makes it difficult to predict the
      strains' response in vivo to these agents. This group has been designated CDC
      oxidizer group 3 (O-3).

PMID- 9620399
TI  - "Flexispira rappini" bacteremia in a child with pneumonia.
AB  - We describe a case of "Flexispira rappini" bacteremia from a 9-year-old girl who
      presented with a 5-day history of fever, productive cough, and malaise. A chest X
      ray result was compatible with right middle lobe pneumonia. Blood culture grew a
      gram-negative spiral fusiform bacterium 2 days after the inoculation. Biochemical
      tests showed the organism to be catalase negative, oxidase positive, sodium
      hippurate hydrolysis negative, and urea hydrolysis negative. 16S rRNA gene
      sequencing identified this organism as "F. rappini," showing a six-base
      substitution from the type strain. This is the first report of "F. rappini"
      bacteremia in a human, suggesting that this organism has the potential of causing
      invasive infection, but its role in pneumonia is uncertain and could be unrelated
      to the bacteremia.

PMID- 9620400
TI  - Quantitation of bacteria in blood of typhoid fever patients and relationship
      between counts and clinical features, transmissibility, and antibiotic
      resistance.
AB  - Salmonella typhi was isolated from 369 and Salmonella paratyphi A was isolated
      from 6 of 515 Vietnamese patients with suspected enteric fever. Compared with
      conventional broth culture of blood, direct plating of the buffy coat had a
      diagnostic sensitivity of 99.5% (95% confidence interval [CI], 97.1 to 100%).
      Blood bacterial counts were estimated by the pour plate method. The median S.
      typhi count in blood was 1 CFU/ml (range, <0.3 to 387 CFU/ml), of which a mean of
      63% (95% CI, 58 to 67%) were intracellular. The mean number of bacteria per
      infected leukocyte was 1.3 (interquartile range [IQR], 0.7 to 2.4) CFU/cell (n =
      81). Children (< 15 years old; n = 115) had higher median blood bacterial counts
      than adults (n = 262): 1.5 (range, <0.3 to 387) versus 0.6 (range, <0.3 to 17.7)
      CFU/ml (P = 0.008), and patients who excreted S. typhi in feces had higher
      bacteremias than those who did not: a median of 3 (range, <0.3 to 32) versus 1
      (range, <0.3 to 68) CFU/ml (P = 0.02). Blood bacterial counts declined with
      increasing duration of illness (P = 0.002) and were higher in infections caused
      by multidrug-resistant S. typhi (1.3 [range, <0.3 to 387] CFU/ml; n = 313) than
      in infections caused by antibiotic-sensitive S. typhi (0.5 [range, <0.3 to 32]
      CFU/ml; n = 62) (P = 0.006). In a multivariate analysis this proved to be an
      independent association, suggesting a relationship between antibiotic resistance
      and virulence in S. typhi.

PMID- 9620401
TI  - Antigenic and genomic diversity of human rotavirus VP4 in two consecutive
      epidemic seasons in Mexico.
AB  - In the present investigation we characterized the antigenic diversity of the VP4
      and VP7 proteins in 309 and 261 human rotavirus strains isolated during two
      consecutive epidemic seasons, respectively, in three different regions of Mexico.
      G3 was found to be the prevalent VP7 serotype during the first year, being
      superseded by serotype G1 strains during the second season. To antigenically
      characterize the VP4 protein of the strains isolated, we used five neutralizing
      monoclonal antibodies (MAbs) which showed specificity for VP4 serotypes P1A, P1B,
      and P2 in earlier studies. Eight different patterns of reactivity with these MAbs
      were found, and the prevalence of three of these patterns varied from one season
      to the next. The P genotype of a subset of 52 samples was determined by PCR.
      Among the strains characterized as genotype P[4] and P[8] there were three and
      five different VP4 MAb reactivity patterns, respectively, indicating that the
      diversity of neutralization epitopes in VP4 is greater than that previously
      appreciated by the genomic typing methods.

PMID- 9620402
TI  - Antimicrobial susceptibilities and molecular epidemiology of Salmonella enterica
      serotype enteritidis strains isolated in Hong Kong from 1986 to 1996.
AB  - The incidence of salmonellosis has been increasing in Hong Kong since 1989. The
      most common Salmonella enterica serotype isolated in 1994 was S. enteritidis. The
      antimicrobial susceptibilities and molecular epidemiology of 275 S. enteritidis
      strains isolated in this locality between 1986 and 1996 were studied. Over 99% of
      the isolates were susceptible to 17 of the 19 antimicrobial agents tested. One
      isolate harbored an autotransferring plasmid that confers resistance to
      tetracycline and trimethoprim-sulfamethoxazole. Another isolate harbored a
      mobilizable plasmid that confers resistance to ampicillin and cephalothin. This
      isolate was found to produce a beta-lactamase with a pI of 5.2. A total of 264
      isolates (96%) were found to harbor one to five plasmids, and the majority (254)
      harbored a 60-kb plasmid. Of these isolates, 94% contained identical 60-kb
      plasmids. Based on plasmid profiles, plasmid and chromosomal fingerprints,
      ribotypes, and randomly amplified polymorphic DNA (RAPD) patterns, 170 (62%)
      isolates were allocated to group 1b. About 90% of isolates had identical or
      similar DNA fingerprints, ribotypes, and RAPD patterns, suggesting that a
      predominant clone of S. enteritidis was circulating in Hong Kong during the
      period being studied.

PMID- 9620403
TI  - Proliferative enterocolitis associated with dual infection with enteropathogenic
      Escherichia coli and Lawsonia intracellularis in rabbits.
AB  - Both enteropathogenic Escherichia coli (EPEC) and an obligate intracellular
      bacterium, previously referred to as an intracellular Campylobacter-like organism
      and now designated Lawsonia intracellularis, have been reported as causes of
      enterocolitis in rabbits. An outbreak of enterocolitis in a group of rabbits,
      characterized by an unusually high rate of mortality, was found to be associated
      with dual infection with EPEC and L. intracellularis. The EPEC strain was found
      to have eaeA gene homology but was negative for afrA homology. The absence of the
      afrA gene, which encodes the structural subunit for the AF/R1 pilus, indicates
      that this rabbit EPEC strain is distinct from the prototypic RDEC-1 strain. This
      finding suggests that rabbit EPEC strains widely reported in Western Europe,
      which lack AF/R1 pili, are also present in rabbits in the United States. Dual
      infection with these two pathogens in rabbits has not been previously reported
      and may have contributed to the unusually high mortality observed in this
      outbreak.

PMID- 9620404
TI  - Detection and identification of Actinobacillus pleuropneumoniae serotype 5 by
      multiplex PCR.
AB  - Serotyping of Actinobacillus pleuropneumoniae is based on detection of the
      serotype-specific capsular antigen. However, not all isolates can be serotyped,
      and some may cross-react with multiple serotyping reagents. To improve
      sensitivity and specificity of serotyping and for early detection, a multiplex
      PCR assay was developed for detection of A. pleuropneumoniae and identification
      of serotype 5 isolates. DNA sequences specific to the conserved export and
      serotype-specific biosynthesis regions of the capsular polysaccharide of A.
      pleuropneumoniae serotype 5 were used as primers to amplify 0.7- and 1.1-kb DNA
      fragments, respectively. The 0.7-kb fragment was amplified from all strains of A.
      pleuropneumoniae tested with the exception of serotype 4. The 0.7-kb fragment was
      not amplified from any heterologous species that are also common pathogens or
      commensals of swine. In contrast, the 1.1-kb fragment was amplified from all
      serotype 5 strains only. The assay was capable of amplifying DNA from less than
      10(2) CFU. The A. pleuropneumoniae serotype 5 capsular DNA products were readily
      amplified from lung tissues obtained from infected swine, although the 1.1-kb
      product was not amplified from some tissues stored frozen for 6 years. The
      multiplex PCR assay enabled us to detect A. pleuropneumoniae rapidly and to
      distinguish serotype 5 strains from other serotypes. The use of primers specific
      to the biosynthesis regions of other A. pleuropneumoniae serotypes would expand
      the diagnostic and epidemiologic capabilities of this assay.

PMID- 9620405
TI  - Hepatitis C virus infections in dialysis centers in The Netherlands: a national
      survey by serological and molecular methods.
AB  - A national survey of hepatitis C virus (HCV) infections among dialysis patients
      in The Netherlands was performed. The study involved 2,653 patients (2,108
      hemodialysis patients and 545 chronic ambulatory peritoneal dialysis [CAPD]
      patients) from 39 of the 49 dialysis centers in the country. Patient sera were
      analyzed by both serological and molecular methods. Screening by a third
      generation enzyme immunoassay (EIA) yielded 79 reactive sera. The presence of
      anti-HCV antibodies was confirmed in 70 patients by a line immunoassay. All
      seropositive samples were tested by reverse transcriptase PCR, and 57 samples
      were found to contain HCV RNA. Of the nine EIA-positive and line immunoassay
      negative or indeterminate samples, four were HCV RNA positive. All seronegative
      samples were screened for the presence of HCV RNA in pools of five sera. Of 2,576
      antibody-negative samples, 6 contained HCV RNA. All antibody-positive and RNA
      positive samples were also tested by a second serological assay. The prevalence
      of HCV infections among Dutch dialysis patients as determined by serology or the
      presence of HCV RNA was 3% (80 of 2,653), i.e., 3.5% (73 of 2,108) in patients
      treated on hemodialysis and 1.3% (7 of 545) in patients on CAPD. Of these 80 HCV
      infected dialysis patients, 67 (84%) were HCV RNA positive. Serological screening
      alone would have diagnosed only 70 infected patients. Therefore, antibody
      screening combined with detection of HCV RNA should be considered as the "gold
      standard" for diagnosing HCV infection in dialysis patients. The prevalence of
      HCV-infected patients in Dutch dialysis centers ranged from 0 to 8%, suggesting
      the existence of local risk factors for acquiring HCV infection. Genotyping
      analysis by reverse hybridization line probe assay revealed the presence of
      genotypes la (23%), 1b (46%), 2 (3%), 2a (13%), 2b (1%), 3a (7%), and 4a (4%). In
      four (6%) samples multiple genotypes were detected. The genotype distribution of
      HCV isolates among Dutch dialysis patients was similar to the distribution among
      nondialysis patients from the Benelux, except for subtype 1a, which was
      significantly more prevalent among dialysis patients. In only one center, a high
      prevalence of an uncommon genotype was suggestive of infection from a common
      source.

PMID- 9620406
TI  - Evaluation of North American antibody detection tests for diagnosis of
      brucellosis in goats.
AB  - The sensitivities and specificities of 17 antibody detection tests for
      brucellosis in goats were estimated. Tests evaluated included the U.S. Department
      of Agriculture (USDA) card test with 8% cell concentration (8%Card), USDA rapid
      automated presumptive test (RAP), Mexican rose bengal plate tests with 8 and 3%
      cell concentrations (8%RB and 3%RB), French rose bengal plate test with 4.5% cell
      concentration (4.5%RB), USDA standard plate test (SPT), USDA buffered acidified
      plate agglutination test (BAPA), USDA and Mexican rivanol tests (URIV and MRIV),
      USDA standard tube tests with Brucella abortus and Brucella melitensis antigens
      (SATA and SATM), serum enzyme-linked immunosorbent assay (ELISA), USDA cold
      fixation complement fixation tests with B. abortus and B. melitensis antigens
      (CFA and CFM), USDA and Mexican milk ring tests (UBRT and MBRT), and a milk
      ELISA. Test sensitivity was evaluated by using two groups of 10 goats
      experimentally infected with B. melitensis or B. abortus and monitored for 24
      weeks. Specificity was evaluated by using 200 brucellosis-free nonvaccinated
      goats from 10 California herds. The 3%RB was considered a good screening test
      because of high sensitivity at week 24 postinfection (90%), ease of performance,
      and low cost. The cold-fixation CFA and CFM had 100% specificity in the field
      study and were considered appropriate confirmatory tests. The milk ELISA was
      significantly more sensitive (P < 0.05) than the UBRT and significantly more
      specific (P < 0.05) than the MBRT. The milk ELISA also had the advantage of
      objectivity and ease of interpretation.

PMID- 9620407
TI  - Detection of circulating Paracoccidioides brasiliensis antigen in urine of
      paracoccidioidomycosis patients before and during treatment.
AB  - For the diagnosis and follow-up of paracoccidioidomycosis patients undergoing
      therapy, we evaluated two methods (immunoblotting and competition enzyme
      immunoassay) for the detection of circulating antigen in urine samples. A complex
      pattern of reactivity was observed in the immunoblot test. Bands of 70 and 43 kDa
      were detected more often in urine samples from patients before treatment. The
      immunoblot method detected gp43 and gp70 separately or concurrently in 11 (91.7%)
      of 12 patients, whereas the competition enzyme immunoassay detected antigenuria
      in 9 (75%) of 12 patients. Both tests appeared to be highly specific (100%),
      considering that neither fraction detectable by immunoblotting was present in
      urine samples from the control group. gp43 remained present in the urine samples
      collected during the treatment period, with a significant decrease in reactivity
      in samples collected during clinical recovery and increased reactivity in samples
      collected during relapses. Reactivity of some bands was also detected in urine
      specimens from patients with "apparent cure." The detection of Paracoccidioides
      brasiliensis antigens in urine appears to be a promising method for diagnosing
      infection, for evaluating the efficacy of treatment, and for detecting relapse.

PMID- 9620408
TI  - Detection of Bacteroides fragilis enterotoxin gene by PCR.
AB  - Bacteroides fragilis constitutes about 1% of the bacterial flora in intestines of
      normal humans. Enterotoxigenic strains of B. fragilis have been associated with
      diarrheal diseases in humans and animals. The enterotoxin produced by these
      isolates induces fluid changes in ligated intestinal loops and an in vitro
      cytotoxic response in HT-29 cells. We developed a nested PCR to detect the
      enterotoxin gene of B. fragilis in stool specimens. After DNA extraction, a 367
      bp fragment was amplified with two outer primers. The amplicon from this reaction
      was subjected to a second round of amplification with a set of internal primers.
      With these inner primers, a 290-bp DNA fragment was obtained which was confirmed
      as part of the B. fragilis enterotoxin gene by Southern blotting with a
      nonradioactive internal probe and a chemiluminescence system. By this approach,
      B. fragilis enterotoxin gene sequences were detected in eight known
      enterotoxigenic human isolates and nine enterotoxigenic horse isolates. No
      amplification products were obtained from DNA extracted from 28
      nonenterotoxigenic B. fragilis isolates or B. distasonis, B. thetaiotaomicron, B.
      uniformis, B. ovatus, Escherichia coli, or Clostridium difficile. The sensitivity
      of this assay allowed us to detect as little as 1 pg of enterotoxin DNA sequences
      or 100 to 1,000 cells of enterotoxigenic B. fragilis/g of stool. Enterotoxin
      production of all isolates was confirmed in vitro in HT-29 cells. A 100%
      correlation was obtained between enterotoxin detection by cytotoxin assay and the
      nested PCR assay. This rapid and sensitive assay can be used to identify
      enterotoxigenic B. fragilis and may be used clinically to determine the role of
      B. fragilis in diarrheal diseases.

PMID- 9620409
TI  - Geographic discrimination of Paracoccidioides brasiliensis strains by randomly
      amplified polymorphic DNA analysis.
AB  - Randomly amplified polymorphic DNA (RAPD) analysis of 33 Paracoccidioides
      brasiliensis strains from Argentina, Brazil, Colombia, Peru, and Venezuela
      produced reproducible amplification products which were sufficiently polymorphic
      to allow differentiation of the strains. Types generated with five primers (OPG
      03, OPG 05, OPG 14, OPG 16, and OPG 18) resulted in a high discriminatory index
      (0.956). The discriminatory index was slightly reduced (0.940) when only two
      primers (OPG 3 and OPG 14) were used. A dendrogram based on these results showed
      a high degree of similarity among the strains, and genetic differences were
      expressed in clusters related to geographical regions but not to pathological
      features of the disease. With a few exceptions, strains were sorted into five
      groups by geographical origin as follows: group I, Venezuelan strains; group II,
      Brazilian strains; group III, Peruvian strains; group IV, Colombian strains; and
      group V, Argentinian strains. The group containing the most disparate strains was
      group V (discriminatory index, 0.633); the discriminatory index for the other
      four groups was 0.824. The use of primer OPG 18 by itself was sufficient to
      discriminate species specificity, and the use of primer OPG 14 by itself was
      sufficient to discriminate among the geographical locations of the strains in the
      sample. This method may be helpful for epidemiological studies of P.
      brasiliensis.

PMID- 9620410
TI  - Identification of Pneumocystis carinii f. sp. hominis gene sequences in filtered
      air in hospital environments.
AB  - To evaluate the risk of a nosocomial spread of Pneumocystis carinii f. sp.
      hominis (P. carinii hominis), air filter samples from rooms of P. carinii
      pneumonia (PCP) patients, adjacent corridors, and other hospital environments
      have been investigated for the presence of P. carinii hominis. Amplified DNA from
      air filters and sputum or bronchoalveolar lavage samples from the PCP patients
      have been genotyped with the P. carinii hominis genes of the mitochondrial large
      subunit (mtLSU) rRNA and the internal transcribed spacers (ITS1 and ITS2) of the
      rRNA. Genotypes of the two loci were identified by direct sequencing, and for
      site 85 of the mtLSU locus, three allele-specific PCR assays were used. P.
      carinii hominis DNA was identified in the air of five of seven PCP patient rooms
      and in the air of two of four air filtrations from the ward corridors. The P.
      carinii hominis genotypes were the same in four of the five room air samples as
      those in the corresponding patients, suggesting a risk of person-to-person
      transmission of P. carinii hominis from PCP patients. Three of 16 air samples
      collected in infectious disease wards without the presence of PCP patients and
      one sample from a cardiology unit in a separate hospital building were also
      positive, which further strengthens the possibility of acquisition of P. carinii
      hominis from the environment.

PMID- 9620411
TI  - Evaluation of a commercially available reverse transcription-PCR assay for
      diagnosis of enteroviral infection in archival and prospectively collected
      cerebrospinal fluid specimens.
AB  - A commercially available reverse transcription (RT)-PCR method (AMPLICOR EV;
      Roche Diagnostic Systems, Inc., Branchburg, N.J.) was evaluated for detection of
      enteroviruses in cerebrospinal fluid from patients with neurological disease.
      This assay was compared with virus isolation in cell culture and an in-house RT
      PCR method designed with a nonoverlapping region of the enteroviral genome. A
      panel of 200 cerebrospinal fluid specimens prospectively collected from patients
      with a wide variety of neurological symptoms, including 50 patients involved in
      three different outbreaks of acute aseptic meningitis, was assayed. A second
      panel of 97 archived cerebrospinal fluid specimens, stored for 2 to 5 years, from
      patients with aseptic meningitis associated with several enterovirus outbreaks
      was also studied. From the first panel, enteroviruses were detected in 13 of 50
      specimens by cell culture (26%), in 43 of 50 specimens by AMPLICOR EV (86%), and
      in 46 of 50 specimens by the in-house assay (92%) from patients with aseptic
      meningitis associated with outbreak and 1 of 29, 3 of 29, and 4 of 29 specimens,
      respectively, from sporadic cases of aseptic meningitis. The remaining 121
      cerebrospinal fluid specimens from patients with other neurological syndromes
      were negative by all tests. From the second panel, enteroviral RNA was detected
      by the AMPLICOR test (31 of 97 specimens, 32%) and the in-house assay (39 of 97
      specimens, 40%). According to our results, patients with aseptic meningitis
      should be analyzed for enteroviral infection in cerebrospinal fluid by RT-PCR
      methods, and the AMPLICOR EV test is a suitable tool for performing such studies.
      Archival cerebrospinal fluid specimens are less suitable for evaluation of the
      performance of RT-PCR methods designed for enterovirus detection.

PMID- 9620412
TI  - Randomly amplified polymorphic DNA genotyping of serogroup A meningococci yields
      results similar to those obtained by multilocus enzyme electrophoresis and
      reveals new genotypes.
AB  - Randomly amplified polymorphic DNA (RAPD) genotyping was applied to one
      representative strain of each of the 84 electrophoretic types (ETs) of Neisseria
      meningitidis serogroup A previously defined by multilocus enzyme electrophoresis
      (MEE) (J.-F. Wang et al., Infect. Immun. 60:5267-5282, 1992). Twenty-seven
      additional isolates comprising six ETs were also tested. MEE and RAPD genotyping
      yielded similar dendrograms at the subgroup level. Similar results were obtained
      by both methods for 18 serogroup A meningococci isolated in The Netherlands
      between 1989 and 1993. Ten of these isolates defined a new subgroup, designated
      subgroup IX. One isolate belonged to the ET-5 complex, normally associated with
      serogroup B strains (D. A. Caugant et al., Proc. Natl. Acad. Sci. USA 83:4927
      4931, 1986). By RAPD genotyping, meningococci can be linked to previously
      characterized genotypes by using a computerized database, and dendrograms based
      on cluster analyses can easily be generated. RAPD analysis offers advantages over
      MEE since intermediate numbers of isolates of serogroup A meningococci can
      quickly be assigned to known subgroups and new subgroups can be defined.

PMID- 9620414
TI  - Isolation of Lautropia mirabilis from oral cavities of human immunodeficiency
      virus-infected children.
AB  - Lautropia mirabilis, a pleomorphic, motile, gram-negative coccus, has been
      isolated from the oral cavities of 32 of 60 (53.3%) children infected with human
      immunodeficiency virus (HIV) and 3 of 25 (12.0%) HIV-uninfected controls; the
      association of L. mirabilis isolation with HIV infection is significant (P <
      0.001). All children in the study, both HIV-infected children and controls, were
      born to HIV-infected mothers. The presence of this bacterium was not associated
      with clinical disease in these children. The HIV-infected children with L.
      mirabilis did not differ from the HIV-infected children without L. mirabilis in
      immunological status, clinical status, or systemic medications. The role of HIV
      infection itself or concomitant factors in the establishment of L. mirabilis in
      the oral cavity remains to be elucidated.

PMID- 9620413
TI  - Monoclonal antibody F89/160.1.5 defines a conserved epitope on the ruminant prion
      protein.
AB  - The transmissible spongiform encephalopathies are a heterogeneous group of fatal
      neurodegenerative disorders occurring in humans, mink, cats, and ruminant
      herbivores. The occurrence of novel transmissible spongiform encephalopathies in
      cattle in the United Kingdom and Europe and in mule deer and elk in parts of the
      United States has emphasized the need for reliable diagnostic tests with
      standardized reagents. Postmortem diagnosis is performed by histologic
      examination of brain sections from affected animals. The histopathological
      criteria for transmissible spongiform encephalopathies include gliosis,
      astrocytosis, neuronal degeneration, and spongiform change. These lesions vary in
      intensity and anatomic location depending on the host species and genetics, stage
      of disease, and infectious agent source. Diagnosis by histopathology alone may be
      ambiguous in hosts with early cases of disease and impossible if the tissue is
      autolyzed. Deposition of the prion protein (an abnormal isoform of a native
      cellular sialoglycoprotein) in the central nervous system is a reliable marker
      for infection, and immunohistochemical detection of this marker is a useful
      adjunct to histopathology. In the present paper we describe monoclonal antibody
      (MAb) F89/160.1.5, which reacts with prion protein in tissues from sheep, cattle,
      mule deer, and elk with naturally occurring transmissible spongiform
      encephalopathies. This MAb recognizes a conserved epitope on the prion protein in
      formalin-fixed, paraffin-embedded sections after hydrated autoclaving. MAb
      F89/160.1.5 will be useful in diagnostic and pathogenesis studies of the
      transmissible spongiform encephalopathies in these ruminant species.

PMID- 9620415
TI  - 16S rRNA sequence diversity in Mycobacterium celatum strains caused by presence
      of two different copies of 16S rRNA gene.
AB  - Direct sequencing of the 16S rRNA gene (16S rDNA) of Mycobacterium celatum
      isolates showed ambiguities, suggesting heterogeneity. Cloned 16S rDNA yielded
      two copies of the gene, which differed by insertion of a thymine at position 214
      and by additional mismatches. Restriction fragment length polymorphism analysis
      confirmed the presence of two copies of 16S rDNA within the bacterial chromosome.

PMID- 9620416
TI  - Evaluation of silica gel packages for transport of Neisseria meningitidis.
AB  - Eight Neisseria meningitidis reference strains, representing six different
      serogroups, were plated on 57 blood agar plates each. The growth was harvested
      and stored in silica gel packages at different temperatures for up to 90 days.
      When held at 4 degrees C, all strains were recovered after 90 days of storage.
      Strains held at room temperature or alternately at 4 degrees C and room
      temperature survived for at least 10 and 17 days, respectively.

PMID- 9620417
TI  - Low-level vancomycin resistance in Clostridium innocuum.
AB  - Low-level vancomycin resistance was observed for 28 clinical Clostridium innocuum
      isolates and C. innocuum NCIB 10674, whereas teicoplanin was active. DNA from
      three clinical isolates and the type strain could not be amplified by PCR with
      primers specific for the genes vanA, vanB, and vanC, suggesting that C. innocuum
      is intrinsically resistant to vancomycin.

PMID- 9620418
TI  - Diagnosis of group A streptococcal necrotizing fasciitis by using PCR to amplify
      the streptococcal pyrogenic exotoxin B gene.
AB  - This study evaluated a PCR assay for detection of the streptococcal pyrogenic
      exotoxin B (speB) gene from tissue biopsy specimens of patients with necrotizing
      fasciitis. speB was detected in specimens from all 10 patients with necrotizing
      fasciitis due to group A streptococcus. The assay was negative for all 11
      patients without culture or serologic evidence of streptococcal infection. These
      results suggest that the detection of speB by PCR may be useful for confirming
      group A streptococcal infection when cultures are negative or not available.

PMID- 9620419
TI  - Invasive infection with Fusarium chlamydosporum in a patient with aplastic
      anemia.
AB  - We report the first case of invasive disease caused by Fusarium chlamydosporum.
      The patient had aplastic anemia with prolonged neutropenia and was treated with
      immunosuppressive therapy. While she was receiving empirical amphotericin B, a
      dark crusted lesion developed on her nasal turbinate. Histologic analysis
      revealed invasive hyaline hyphae and some darkly pigmented structures that
      resembled conidia of dematiaceous molds. Only after the mold was grown in culture
      were characteristic colonial morphology, phialides, conidia, and chlamydospores
      evident, thus permitting the identification of F. chlamydosporum. This case
      illustrates the ever-increasing spectrum of pathogenic Fusarium spp. in
      immunocompromised patients and emphasizes the potential pitfalls in histologic
      diagnosis, which may have important treatment implications.

PMID- 9620420
TI  - Non-O157:H7 Stx2-producing Escherichia coli strains associated with sporadic
      cases of hemolytic-uremic syndrome in adults.
AB  - From August 1996 to May 1997, six verotoxin-producing Escherichia coli (VTEC)
      strains were isolated from stool specimens of adults suffering from hemolytic
      uremic syndrome (HUS). All the isolates were stx2 positive and belonged to
      different serotypes: O6:H4, O91:H10, O91:H21, O rough:H16, OX3:H-, and O
      nontypeable: H-. The enterohemolysin (Ehly)-encoding genes were detected in two
      isolates, and none of the isolates harbors the intimin (Eae)-encoding gene. These
      findings suggest that stx2-positive non-O157:H7 VTEC is a major cause of HUS in
      adults and that several sources of pathogens are responsible for local endemic
      infections.

PMID- 9620421
TI  - Peritonitis associated with vancomycin-resistant Lactobacillus rhamnosus in a
      continuous ambulatory peritoneal dialysis patient: organism identification,
      antibiotic therapy, and case report.
AB  - A case of Lactobacillus rhamnosus-associated peritonitis in a patient undergoing
      continuous ambulatory peritoneal dialysis is reported. The patient was treated
      with vancomycin after isolation of glycopeptide-susceptible coagulase-negative
      staphylococci. After a skin rash developed, vancomycin was discontinued and
      replaced with teicoplanin. Seven weeks after the glycopeptide therapy was
      discontinued, a Lactobacillus strain was isolated in pure cultures. The isolate
      was identified first incorrectly as L. acidophilus but later correctly as L.
      rhamnosus. Antibiotic susceptibility testing showed that the isolate was
      resistant to glycopeptides but susceptible to several other antibiotics. The
      antibiotic treatment was then switched to imipenem and was successful.

PMID- 9620422
TI  - High human herpesvirus 8 seroprevalence in the homosexual population in
      Switzerland.
AB  - The seroprevalence of human herpesvirus 8 (HHV-8) in the Swiss population was
      investigated. By enzyme-linked immunosorbent assay, sera reactive to the
      recombinant HHV-8 antigen orf 65.2 were found in 24% of human immunodeficiency
      virus (HIV)-positive patients without and in 92% of HIV-positive patients with
      Kaposi's sarcoma. Surprisingly, 20% of homosexual HIV-negative men, versus only
      7% of heterosexual HIV-negative individuals and 5% of blood donors, had
      antibodies to HHV-8.

PMID- 9620423
TI  - Typing of human Campylobacter jejuni isolates in Finland by pulsed-field gel
      electrophoresis.
AB  - A total of 69 pulsed-field gel electrophoresis (PFGE) types were identified among
      176 Campylobacter jejuni isolates from Finnish patients. In two geographic areas
      studied, five predominant PFGE types comprised over 40% of the isolates. One
      third of the isolates had unique PFGE types. In small outbreaks, identical PFGE
      patterns were demonstrated, indicating a common source of infection.

PMID- 9620424
TI  - Antimicrobial susceptibility testing of Bilophila wadsworthia isolates submitted
      for routine laboratory examination.
AB  - MICs of antibiotics against Bilophila wadsworthia isolates were measured by agar
      and broth microdilution with pyruvic acid and by Etest. The inoculum size
      influenced greatly agar dilution. Despite discrepancies in MICs depending on the
      measurement method used, clindamycin consistently showed potent activity. Broth
      microdilution and Etest appear to be candidates for laboratory susceptibility
      testing.

PMID- 9620425
TI  - Reverse transcriptase PCR amplification of Rickettsia typhi from infected
      mammalian cells and insect vectors.
AB  - We developed a reverse transcriptase PCR assay to detect expression of 120- and
      17-kDa antigen genes in Rickettsia typhi. Infected Vero cell and flea RNAs were
      reverse transcribed by using random hexamers. The cDNA was amplified by using
      high concentrations of primer and template in an inexpensive, nonradioactive
      assay.

PMID- 9620427
TI  - Stabilized, freeze-dried PCR mix for detection of mycobacteria.
AB  - We report here the development of a freeze-drying procedure allowing
      stabilization at ambient temperature of preoptimized, premixed, and predispensed
      PCR mixes aimed at the detection of mycobacteria in clinical materials. The
      freeze-dried mixes retained activity at 4 degrees C and at 20 degrees C for 1
      year and for 3 months at 37 degrees C, as judged by their performance with 50 and
      500 fg of purified Mycobacterium bovis BCG target DNA.

PMID- 9620426
TI  - Multiplex PCR for enterotoxigenic, attaching and effacing, and Shiga toxin
      producing Escherichia coli strains from calves.
AB  - A multiplex PCR was developed to identify enterotoxigenic, attaching and
      effacing, and Shiga toxin-producing Escherichia coli strains by amplifying genes
      encoding K99 and F41 fimbriae, heat-stable enterotoxin a, intimin, and Shiga
      toxins 1 and 2. This multiplex PCR was specific and sensitive. It will be useful
      for identification of E. coli strains which cause diarrhea in calves.

PMID- 9620428
TI  - A PCR specific for Escherichia coli O157 based on the rfb locus encoding O157
      lipopolysaccharide.
AB  - A PCR was developed for the detection of Escherichia coli O157 based on the rfbE
      O-antigen synthesis genes. A 479-bp PCR product was amplified specifically from
      E. coli O157 in cell lysates containing 200 or 2 CFU following crude DNA
      extraction. The PCR detected < 1 CFU of E. coli O157 per ml in raw milk following
      enrichment.

PMID- 9620429
TI  - Conservation of restriction sites in isolates of Streptococcus pneumoniae with
      diverse restriction fragment patterns.
AB  - Separation of large restriction fragments by pulsed-field gel electrophoresis is
      a commonly used method for epidemiological typing of Streptococcus pneumoniae and
      many other bacterial species. Information on the genetic changes underlying the
      restriction fragment polymorphisms that allow discrimination between isolates is
      scarce. In this study fragments adjacent to ApaI sites in a clinical isolate of
      S. pneumoniae were cloned and used to probe HindIII and HindIII-plus-ApaI genomic
      DNA digests from other isolates with very different ApaI fragment patterns. If
      for a given isolate the HindIII fragment detected by the probe was reduced in
      size on digestion with ApaI, it was deduced that the ApaI site was conserved in
      that isolate. The results demonstrate that of six ApaI sites in PN93/908
      examined, five were retained in 11 genetically different isolates and one was
      retained in 2 isolates but lost in 9 others. It was concluded that point
      mutations at restriction sites are unlikely to account for the restriction
      fragment length polymorphism observed and that much of the polymorphism may be
      due to DNA rearrangements, possibly resulting from the insertion or deletion of
      mobile DNA elements.

PMID- 9620430
TI  - Positive result by serology indicates active Helicobacter pylori infection in
      patients with atrophic gastritis.
AB  - Patients with atrophic corpus gastritis and elevated Helicobacter pylori antibody
      titers but 13C-urea breath test (13C-UBT) and histology results negative for H.
      pylori were randomized into eradication therapy or follow-up only. Antibody
      levels decreased significantly in six out of seven patients in the eradication
      group, while in the follow-up group, the titers declined in only one out of eight
      patients. In patients with atrophic corpus gastritis, positive serology results
      may indicate an ongoing infection in spite of negative 13C-UBT and histology
      results.

PMID- 9620431
TI  - Defective human T-cell lymphotropic virus type I (HTLV-I) provirus in 10 Chilean
      seronegative patients with tropical spastic paraparesis or HTLV-I-associated
      myelopathy.
AB  - We studied the presence of tax and ltr genes from human T-cell lymphotropic virus
      type I (HTLV-I) provirus in the peripheral blood mononuclear cells from 15
      seronegative patients with tropical spastic paraparesis or HTLV-I-associated
      myelopathy by PCR. Only a region of the tax gene from 10 patients was amplified.
      The nucleotide homologies of six Chilean isolates to the ATK-1 clone ranged
      between 98.7 and 99.4%.

PMID- 9620432
TI  - Blinded, externally controlled multicenter evaluation of light microscopy and PCR
      for detection of microsporidia in stool specimens. The Diagnostic Multicenter
      Study Group on Microsporidia.
AB  - The quality parameters for the detection of microsporidia in identical sets of 50
      stool samples were determined for six laboratories where technicians used light
      microscopy and for six laboratories where technicians used PCR. The average
      overall sensitivities were 67% (89% for patient samples only) for the PCR
      laboratories and 54% (80% for patient samples only) for the light microscopy
      laboratories. Specificities were 98 and 95%, respectively. Differences in results
      were most apparent between the individual laboratories rather than between the
      two major methods used.

PMID- 9620433
TI  - Microbiological diagnosis of brucellosis.

PMID- 9620434
TI  - Spores of Henneguya salminicola in human stool specimens.

PMID- 9620435
TI  - Identification of a UPTG inhibitor protein from maize endosperm: high homology
      with sucrose synthase protein.
AB  - A thermolabile UPTG inhibitor protein (IP) was isolated and purified from a
      developing maize endosperm preparation. High homology of two internal peptides of
      IP with known plant sucrose synthase (SS) sequences suggested that IP might be
      related somehow with SS. IP and SS activities were found in the same preparation
      and showed thermolability between 60-65 degrees C. IP and SS activities presented
      the same ionic charge and molecular mass in native conditions (Mono Q and
      Superose-12 columns chromatographies). Western blot experiments with an anti-SS
      antibody as well as with an anti-IP antibody showed a single 80 kDa polypeptide
      band where IP and SS activities were present. Anti-SS antibody can neutralize SS
      as well as IP activities in a neutralization assay. It was found that in the
      maize mutant shrunken-1, lacking SS1 protein, the UPTG activity was not
      inhibited. Furthermore, the solubilized preparation of the sh1 endosperm is
      unable of inhibiting UPTG activity from potato tuber. The high correlation
      between IP and SS properties suggests that IP might be in fact a form of SS.
      Moreover, the relation between IP and the SS1 isoform is discussed. So, a new
      biological activity of SS is suggested.

PMID- 9620437
TI  - Structure of heparan sulfate: identification of variable and constant
      oligosaccharide domains in eight heparan sulfates of different origins.
AB  - The use of specific enzymes (heparinase and heparitinases from Flavobacterium
      heparinum, endoglucuronidase, alphaN-acetylglucosaminidase and beta-glucuronidase
      from the mollusc Anomalocardia brasiliana) and chemical methods (nitrous acid
      degradation, hydrazine N-deacetylation and borohydride reduction), led to the
      proposal of the total sequence of a heparan sulfate derived from bovine pancreas
      and partial sequences of heparan sulfates from different origins (bovine: lung,
      liver, brain; hog: liver, brain; rabbit liver; dog liver). It was shown that all
      the heparan sulfates contain common structural features such as: a N-acetylated
      and a N-sulfated domain made of glucuronic acid-containing disaccharides and a
      more sulfated region made of iduronic acid-containing disaccharides. Separating
      the two domains a peculiar tetrasaccharide made of GlcNAc-(alpha1-4)-IdoUA
      (alpha1-4)-GlcNS-(alpha1-4)-IdoUA was identified in all the heparan sulfates
      analyzed. It was also shown that the non-reducing ends of the heparan sulfates
      contain the monosaccharides glucosamine N-sulfate and/or glucosamine 2,6
      disulfate.

PMID- 9620436
TI  - Studies on sucrose-phosphate synthase from rice leaves.
AB  - Sucrose-phosphate synthase (SPS, EC 2.4.1.14) biochemical properties and peptide
      composition have been analyzed in rice leaf seedlings. SPS was purified using
      DEAE-Sephacel chromatography, gel filtration on Sepharose 6B and anion exchange
      chromatography on Mono Q. At this stage two enzyme forms (SPS-I and -II) were
      separated. SPS-II was purified 90-fold; however, SPS-I presented a lower specific
      activity regarding the previous purification step and an unstable activity. Both
      enzyme forms had similar apparent Km values for Fru-6P but the SPS-I Km for UDP
      Glc was ca. 10-fold higher than the SPS-II one. In addition, they differentiate
      in the capacity of being modulated by Glc-6-P and Pi: while SPS-II activity was
      inhibited by Pi and activated by Glc-6-P, SPS-I was not affected by either
      effectors. A native molecular mass of ca. 420 kDa was found by gel filtration. In
      SPS expression analysis using leaf rice and wheat germ SPS antibodies, a 116 kDa
      polypeptide was revealed in rice leaf extracts and no polypeptide was
      immunoactive in rice roots.

PMID- 9620438
TI  - The reductive modulation of chloroplast fructose-1,6-bisphosphatase by
      tributylphosphine and sodium borohydride.
AB  - The cleavage of disulfide bonds is the major modification of chloroplast fructose
      1,6-bisphosphatase when the light-mediated ferredoxin-thioredoxin system enhances
      the activity of the enzyme. In vitro, only thiol-bearing compounds are functional
      in the stimulation of fructose 1,6-bisphosphate hydrolysis. This investigation
      was undertaken to determine the effectivity of other reductants for enhancing the
      catalytic capacity. In the presence of 1 mM fructose 1,6-bisphosphate and 0.1 mM
      Ca2+, the five-fold activation triggered by 3.5 mM tributylphosphine is further
      potentiated by 15% (v/v) 2-propanol. When the enzyme is incubated in the presence
      of 0.15 M sodium trichloroacetate in place of the cosolvent, NaH4B initially
      stimulates the activity but subsequently causes the inactivation of the enzyme. A
      model developed to analyze this dual effect suggests that the concerted action of
      fructose 1,6-bisphosphate, Ca2+ and trichloroacetate yields an enzyme form that
      is slightly activable by reduction (t0.5 = 28 min.). However, chloroplast
      fructose-1,6-bisphosphatase becomes highly sensitive to trichloroacetate
      inactivation (t0.5 = 5 min.) when NaH4B reduces fructose 1,6-bisphosphate. Hence,
      the thiol/disulfide exchange constitutes a particular case of reductive
      mechanisms that stimulate the activity of chloroplast fructose-1,6
      bisphosphatase.

PMID- 9620439
TI  - Rat liver genesine: a biochemical approach.
AB  - Genesine, the naked autoglucosylating protein involved in glycogen biosynthesis,
      was partially purified from rat liver and some of its biochemical properties were
      characterized. Its activity was strongly activated by Mn2+ and two-pH optimums
      were obtained. UDP-14C-Glc was the preferred glucosyl donor substrate, but also
      UDP-14C-Xyl was. It was additionally found that more than one glucose was
      transferred to the protein or to that alpha1,4 glucan already linked to the
      protein from UDP-Glc. Glucose, maltose, xylose and UDP were inhibitors of
      genesine activity.

PMID- 9620440
TI  - Structure of an extracellular mannosylated cellulose produced by a mutant strain
      of Xanthomonas campestris.
AB  - Structural studies were performed in two atypical polysaccharides, PS-1 and PS-2
      isolated from the broth of a Tn5 mutant strain of Xanthomonas campestris. Sugar
      composition, methylation and nuclear magnetic resonance analyses were determined.
      PS-1 is composed by repeating trisaccharide units containing D-glucose, D-mannose
      and having the structure. carbohydrate sequence [see text]. Preliminary studies
      on the PS-2 show a polymer composed in a large extent of rhamnose. Unexpectedly,
      this polysaccharide is soluble in alcoholic solutions.

PMID- 9620441
TI  - Glycogen brain branching enzyme.
AB  - Rat brain glycogen branching enzyme was partially purified in order to elucidate
      its mechanism of action. The alpha1,4-alpha1,6-glucan polysaccharide was
      synthesized using rat brain branching enzyme under two different elongation
      conditions: Glc-1-P and phosphorylase or UDP-Glc and glycogen synthase. The
      products obtained demonstrated that the cpolysaccharides synthesized (pattern of
      the spectra obtained in the presence of Krisman's reagent, lambda max, parameter
      A and R, % beta-amylolysis and degree of branching) under different incubation
      times are nearly constant. These results imply that the degree of branching of a
      polysaccharide depends only on the enzyme specificity.

PMID- 9620442
TI  - The pamamycins: developmental autoregulators and antibiotics from Streptomyces
      alboniger. A review and update.
AB  - A brief review and update of current studies on the pamamycins is presented. The
      pamamycins are a group of macrolides isolated from Streptomyces alboniger which
      function as autoregulators in streptomycetes. At low concentrations, they
      stimulate the formation of aerial mycelium and, at higher concentrations, they
      inhibit the growth of these organisms. In addition, the pamamycins have potent
      antibiotic activity against gram-positive bacteria, fungi and mycobacteria. The
      possible mode of action of these compounds is discussed, together with their
      possible value against multiple antibiotic-resistant M. tuberculosis.

PMID- 9620443
TI  - Reaction of beta-lapachone and related naphthoquinones with 2-mercaptoethanol: a
      biomimetic model of topoisomerase II poisoning by quinones.
AB  - 1,2-Naphthoquinones, such as beta-lapachone, 4-alkoxy-1,2-naphthoquinones, and
      tetrahydrofuran-1,2-naphthoquinones, react rapidly with 2-mercaptoethanol in
      benzene to give 1,4-, 1,2-, 1,3- and 1,6-Michael-type adducts that are formed by
      the addition of the thiol group to the quinone ring. Menadione (2-methyl-1,4
      naphthoquinone) reacts with the thiol reagent very slowly under the same reaction
      conditions. Although the formation of the adducts can be followed by 1H-NMR,
      attempts to isolate the adducts failed due to their retroconversion to the
      starting products. On addition of a Lewis acid, however, the adducts undergo
      cyclization reactions that give stable derivatives that can be isolated and
      characterized. Determination of the structures of the derivatives allowed for the
      identification of the adducts from which they originated. Thus, beta-lapachone
      and 2,3-dinordunnione underwent 1,4- and 1,2-Michael type additions to the
      quinone ring, while 4-pentyloxy-1,2-naphthoquinone underwent two simultaneous
      Michael additions to the quinone ring of the naphthoquinone. Menadione underwent
      a single 1,3-addition. The alkylation rates of the thiol group of 2
      mercaptoethanol by the naphthoquinones parallel the naphthoquinones efficiencies
      in inducing DNA cleavage through DNA-bound topoisomerase II. These results
      support our hypothesis that the cytotoxic effect of the naphthoquinones derive,
      at least in part, from their alkylation of exposed thiol residues on the
      topoisomerase II-DNA complex.

PMID- 9620444
TI  - Characterization of a novel translational inhibitor from Leishmania mexicana
      promastigotes.
AB  - An inhibitory activity blocking protein synthesis elongation in several
      eukaryotic systems has been detected in Leishmania mexicana extracts. This
      factor, which competes with aminoacylation of tRNA and also affects the
      subsequent polymerization step, is a strong inhibitor of polypeptide synthesis
      induced by poly U in wheat-germ extracts or by endogenous mRNAs in rat liver cell
      free systems. The purified translational inhibitor has shown to be essentially
      free of proteins. Several chemical and biochemical properties of the inhibition
      factor have supported the conclusion that it behaves as a 200 bases RNA with a
      high content of secondary structure.

PMID- 9620445
TI  - Characterization of OXA-9, a beta-lactamase encoded by the multiresistance
      transposon Tn1331.
AB  - The enzyme OXA-9, an oxacillinase-carbenicillinase, is encoded by the blaOXA-9
      gene which was originally found within the structure of Tn1331, a multiresistance
      transposon first isolated from a clinical Klebsiella pneumoniae strain. Studies
      to characterize OXA-9 demonstrated that it has a pI of 6.9 and the optimal pH for
      enzyme activity was between 7.7 and 8.2. When total soluble extracts were
      preincubated at 37 degrees C and at 42 degrees C, enzyme activity decayed to
      approximately 56% of the original value after 6 hrs. at 37 degrees C and to 50%
      after 30 min. at 42 degrees C. Enzymatic activity of OXA-9 was inhibited in the
      presence of p-chloromercuribenzoate, cloxacillin and clavulanic acid, but not by
      200 mM sodium chloride. The inhibition by p-chloromercuribenzoate may indicate
      the presence of a cysteine residue playing a role in the catalytic activity of
      the enzyme. The OXA-9 enzyme was released by osmotic shock of E. coli cells
      harboring a recombinant clone including the blaOXA-9 gene indicating that it is
      located in the periplasmic space of the cells. The OXA-9 enzyme was purified from
      soluble protein extracts of E. coli cells carrying a recombinant clone including
      the blaOXA-9 by ion exchange chromatography.

PMID- 9620446
TI  - The human breast cancer cell line IIB-BR-G has amplified c-myc and c-fos
      oncogenes in vitro and is spontaneously metastatic in vivo.
AB  - IIB-BR-G is an undifferentiated, highly heterogeneous, hormone receptor negative
      human breast cancer cell line previously established in our laboratory from a
      patient's primary tumor. An in vitro growing cell line (IIB-BR-G) and a
      xenotransplanted tumor growing in nude mice (IIB-BR-G(NUDE)) were derived. To
      further characterize these systems, immunocytochemical analysis was performed for
      differentiation antigens (PEM 200 kDa, CEA, NCA 90 kDa), blood-group related
      antigens (Le(x), sTn), oncogenes and tumor suppressor gene products (Her-2/neu
      protein, p53), metastasis-related cathepsin D and CD63/5.01 Ag, and the chemokine
      monocyte chemotactic protein 1 (MCP-1). Expression of markers was heterogeneous
      in these different systems. Previously reported karyotypic analysis has shown
      extensive chromosomal alterations including double min. Searching for oncogene
      amplification, we detected augmented copy number of c-myc and c-fos, the last one
      with two rearranged fragments. No amplification was found for c-erbB-2 in the
      cell line or in IIB-BR-G(NUDE), although this oncogene was amplified in the
      patient's primary tumor DNA. The differences observed between the patient's
      tumor, the cell line and the IIB-BR-G(NUDE) tumors are probably due to clonal
      expansion of cell variants not present in the original tumor. Electron microscopy
      of IIB-BR-G growing cells revealed epithelial characteristics with abundant dense
      granules, presumably secretory, distributed all over the cytoplasm and great
      nuclear pleomorphism. In vitro, IIB-BR-G cells showed a significant number of
      invading cells by Matrigel assay. After nearly 40 sequential subcutaneous
      passages of the original xenograft through nude mice, 80% of recipients developed
      spontaneous metastases, primarily to the lung and lymph nodes. Since this
      experimental model allowed to analyze changes produced in cancer cells from the
      primary tumor during adaptation to in vitro and in vivo growth, our results
      provide novel insights on the behaviour of hormone independent metastatic breast
      cancer.

PMID- 9620447
TI  - Localization of the different hepatitis C virus core gene products expressed in
      COS-1 cells.
AB  - In this study we have investigated the subcellular localization in transfected
      COS-1 cells of the two major forms of the hepatitis C virus core protein: the
      immature protein of 191 residues (p21) and its proteolytically cleaved product of
      173 residues (p19). In this study, and unlike previous investigations, we have
      been able to distinguish separately the localization of p21 from p19. This was
      achieved by the addition of a C-terminal HSV Tag to the p21 full coding sequence,
      and exploiting the fact that it is subsequently lost in the p19 product. In order
      to obtain an accurate localization of both p21 and p19 we used a mouse anti-HSV
      Tag MAb together with a human anti-core MAb (B12.F8) to perform double
      immunofluorescence studies. The results have shown that p21 is always localized
      around the nuclear envelope. On the other hand, p19 can be found diffused in the
      cytoplasm to different degrees. These in vivo results reinforce the proposed
      links between the regulated processing of the hepatitis C virus core protein and
      the possibility that this may contribute towards the regulation of its diverse
      biological functions.

PMID- 9620448
TI  - Membrane-bound cysteine proteinase isoforms in different developmental stages of
      Trypanosoma cruzi.
AB  - Cysteine proteinase isoforms, immunologically cross-reactive with cruzipain and
      with a similar apparent molecular mass, have been identified in epimastigotes of
      Trypanosoma cruzi by extraction and phase partition using the detergent Triton X
      114. These isoforms are concentrated in the microsomal fraction obtained after
      differential centrifugation, which is known to consist essentially of plasma
      membrane, can be labelled by incubation of live parasites with sulfo-NHS-biotin,
      and bind to cystatin-sepharose affinity columns. They are present, albeit with a
      different electrophoretic pattern, in the epimastigote, amastigote and
      trypomastigote stages of the parasite.

PMID- 9620449
TI  - Streptomycin bactericidal action is dependent on polyamine endogenous levels in
      E. coli.
AB  - E. coli polyamine-supplemented and depleted cultures showed an important
      difference in survival to streptomycin; the bactericidal effect of the antibiotic
      was remarkably higher in cells with normal levels of polyamines. Similar results
      were observed with kanamycin. Analysis of the polyamine-containing cells pulse
      labelled with 35S-methionine during streptomycin action indicated that the
      amounts of newly-synthesized peptides in various subcellular fractions was
      different from the amounts formed in the untreated controls; the most dramatic
      change was found in the residual particulate fraction where the antibiotic
      treatment caused a 3-fold increase of radioactive proteins. On the contrary,
      equivalent amounts of labelled peptides were detected in the different fractions
      prepared from polyamine-depleted bacteria incubated with or without antibiotic.
      In this case the corresponding residual fraction was only slightly increased.
      Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the different
      fractions showed some changes elicited by streptomycin in the protein patterns of
      polyamine-containing bacteria, especially in the residual fractions. The
      electrophoretic profile corresponding to deprived cells was very similar in all
      cases. The role of polyamines in the conformation of the outer membrane and in
      the correct assembly of ribosomes is discussed on account of the enhancing effect
      of these polycations on the bactericidal action of streptomycin.

PMID- 9620450
TI  - Nitric oxide synthase induction in lines of macrophages from different anatomical
      sites.
AB  - Induction of nitric oxide synthase (iNOS) and nitric oxide (NO) production have
      been demonstrated using three macrophage cell lines from different anatomical
      sites, which had been immortalized using a rapid and convenient procedure
      previously described. Lysis of tumor cells presumably was caused by NO
      accumulation in the supernatants of cultures of the three cell lines after
      induction with a mixture of recombinant murine interferon gamma (rMuIFNgamma) and
      lipopolysaccharide (LPS). Induction by these two biological response modifiers
      (BRM) caused lysis of tumor cells and was repressed by addition of 1 microM
      (final concentration) of methyl-L-arginine (MMA) to the mixture during induction
      of the enzyme. Research using readily generated macrophage cell lines may
      facilitate clarify basic aspects of iNOS induction in these cells.

PMID- 9620451
TI  - Platelet endothelial cell adhesion molecule-1 expression during mouse
      postimplantation development.
AB  - With the aim to analyze the ontogeny of the mouse endothelium, monoclonal
      antibody (mAb) MEC 13.3 was used for the immunohistochemical staining of frozen
      sections of different stages of mouse embryo development. This mAb specifically
      recognizes membrane reinforcement of endothelial cells (EC) from mouse blood
      vessels, indicating the expression of a molecule related to the murine form of
      PECAM-1/CD31. The present study reports the expression of the murine PECAM-1/CD31
      antigen, observed with the peroxidase-antiperoxidase technique, in a single cell
      type, with a typical non-differentiated morphology at an early stage of mouse
      postimplantation embryos. A progressive increase in the number of this cell type
      was observed in the early stages of murine development, but few were detected at
      mature stages. On the other hand, EC in days 9.5, 14.5 and 19.5 postcoitum
      embryos were also recognized by the same mAb MEC 13.3 allowing the recognition of
      a cell type related directly or indirectly to vascular network development.

PMID- 9620452
TI  - TGF-beta1 up-regulates the mRNA for the Na+/Ca2+ exchanger in neonatal rat
      cardiac myocytes.
AB  - Northern analyses of neonatal cardiac myocytes demonstrated that TGF-beta1 (5
      ng/ml) stimulates and IL-1beta (5 ng/ml) decreases the steady-state levels of the
      mRNA coding for the Na+/Ca2+ exchanger. This is in agreement with the effects of
      TGF-beta1 and IL-1beta on beating rate and calcium uptake, suggesting that such
      effects might be mediated, at least partially, through up-regulation of the
      Na+/Ca2+ exchanger. Basal and TGF-beta1 stimulated mRNA levels were inhibited by
      the PKC inhibitors H7 (10 microM) and GF109203X (250 nM). In addition, apigenin
      (12.5 microM), a MAP kinase inhibitor, was able to inhibit basal mRNA levels for
      the exchanger. Cycloheximide (35.5 microM) had no effect on basal mRNA levels for
      the exchanger but steady-state levels were diminished in cells treated with TGF
      beta1. Finally, actinomycin D (10 microM) inhibited both basal and TGF-beta1
      stimulated mRNA levels, though with a more pronounced effect in the presence of
      TGF-beta1. These results suggest that a complex mechanism of regulation exists
      for the exchanger and that PKC and possibly MAP kinases might be involved. The up
      regulation of this important protein for calcium extrusion, induced by TGF-beta1,
      might prepare cells to better overcome the calcium overload which occurs under
      cellular stress and might explain some of the cytoprotective effects of TGF
      beta1.

PMID- 9620453
TI  - The early expression of Rev-erbbeta occurs in the developing nervous system of
      mouse embryo.
AB  - The orphan ligand nuclear receptor Rev-erbbeta acts in vitro as a negative
      regulator of transcription. However, its precise physiological role is still
      unknown. As a first attempt to better understand its biological function, we have
      studied the distribution and the localization of the Rev-erbbeta mRNA transcripts
      in different mouse embryonal carcinoma cell lines, in mouse embryos and adult
      tissues. Our results indicated that Rev-erbbeta transcripts are present in both
      the non-differentiated and differentiated F9 cells into either parietal or
      visceral endoderm. At 12.5 days of gestation (E12.5) of mouse embryos, Rev
      erbbeta transcripts were localized only in the developing nervous system. In
      contrast, at later stages of development as well as in the adult, its messengers
      were widely distributed. These results suggest that Rev-erbbeta may have
      different roles at the different stages of mouse development, with a more
      specific role in the nervous system at earlier stages.

PMID- 9620454
TI  - An improvement in the dissociating properties of sodium dodecyl sulfate
      containing sample buffers used in polyacrylamide gel electrophoresis.
AB  - Protein complexes present different degrees of stability. We have previously
      described a glycoprotein from Bacillus thuringiensis that appeared as a multimer
      unable to be dissociated by the usual SDS-containing sample buffers of pH 6.8. In
      order to dissociate the complex, a SDS-containing sample buffer of pH 9 was
      described. In the present report three additional protein complexes with
      different degrees of stability and the effect of that dissociating sample buffer
      are described. The study of SDS critical micellar concentration values as a
      function of pH explains the improvement of dissociating properties at pH 9.

PMID- 9620455
TI  - Postinfarction ventricular septal defect.
AB  - Despite improved screening and diagnostic capabilities for the presence of
      coronary artery disease (CAD), with the promise of improved outcomes from earlier
      therapeutic interventions, postinfarction ventricular septal perforation (VSD)
      continues to be a very difficult therapeutic challenge. In our experience with
      VSD, the incidence of this complication per year has decreased, almost certainly
      related to earlier and more effective medical therapy in patients with CAD. By
      contrast, the outcomes of surgical repair have not improved, even with an
      aggressive strategy about bypassing involved coronary arteries. Furthermore, the
      earliest possible surgical approach and the incorporation of a number of
      technical advances, especially those relating to myocardial preservation, have
      not had an apparent effect. Because the number of patients who underwent
      operation is small, it is not possible from our single-institutional experience
      to define statistical significance to our continuing observations of this
      condition, suggesting that the clinical spectrum of postinfarction VSD is still
      evolving. Important changes appear to be associated with an increase in the
      number of female patients observed (60%), in contrast to their lesser frequency
      of uncomplicated coronary bypass (18%) and a change in the anatomic substrate,
      with posterior infarctions and rupture now accounting for 73% of cases at Cedars
      Sinai. For the present, earliest possible surgical intervention to minimize the
      severity of multi-organ failure and use all of the advanced therapeutic
      modalities of cardiac support and surgical therapy that are available continues
      to be indicated. For the long term, continuing advances in the earlier diagnosis
      and more aggressive management of CAD, especially in females, may hold the best
      promise for a continued decrease in the occurrence of this very difficult-to
      treat postinfarction complication.

PMID- 9620456
TI  - Postinfarction ventricular septal rupture.
AB  - Postinfarction ventricular septal rupture is an uncommon but serious complication
      of acute myocardial infarction. Although I have tried various methods for
      repairing postinfarction septal defects, I recently began to use an exclusion
      technique, which is an extension of the intracavitary repair method that I use to
      treat ventricular aneurysms. This exclusion technique yields satisfactory results
      (early mortality rate, 36.4%), even in patients in severe cardiogenic shock.

PMID- 9620457
TI  - Surgical repair of postinfarction ventricular septal defect by infarct exclusion.
AB  - Repair of postinfarction ventricular septal defect (VSD) by infarct exclusion has
      been used for a decade in our unit. It involves securing a glutaraldehyde
      preserved bovine pericardial patch to the endocardium of the left ventricle all
      around the necrotic myocardium to exclude the VSD and the infarct from the left
      ventricular cavity. Fifty-two patients with postinfarction VSD underwent this
      type of repair from 1987 to 1996. Thirty-four patients were in shock when
      undergoing operation; 26 had anterior VSD and 26 had posterior. Ten patients died
      perioperatively, for surgical mortality of 19%. Three patients developed
      recurrent VSD; one died and two survived. Preoperative cardiogenic shock and age
      older than 70 years were associated with an increased operative mortality.
      Operative survivors were followed up from 6 to 135 months, mean of 65 months. The
      actuarial survival at 8 years was 59% +/- 6%. Repair of postinfarction VSD by
      infarct exclusion is a relatively simple operative procedure and seems to have
      improved the results of surgery in patients with posterior VSD.

PMID- 9620458
TI  - Postinfarction ventricular septal rupture: the Wessex experience.
AB  - Surgical repair of a postinfarct ventricular septal defect (VSD) remains a
      difficult surgical challenge associated with a significant operative mortality.
      Between 1972 and 1995, 179 patients with a postinfarct VSD have undergone
      operation in this institution. There were 118 males and 61 females, with a mean
      age of 66 years (range 43 to 80). Operative mortality was 26.7%. Surgery was
      deferred until 1 month after the septal rupture in 29 patients, with these
      labeled as having a chronic VSD. The remaining 150 underwent operation on within
      1 month of infarction and are described as having an acute VSD. For those with an
      acute VSD, factors significantly associated with an increased risk of 30-day
      mortality included preoperative New York Heart Association status (P = .04), site
      of myocardial infarction (inferior worse than anterior) (P = .004), cross-clamp
      time (P = .05) and cardiopulmonary bypass time (P = .0001) (logistic regression).
      On multiple logistic regression, only cardiopulmonary bypass time remained
      significant. Survival including in-hospital mortality at 5 and 10 years was 49%
      +/- 4% and 31% +/- 5% and excluding in-hospital mortality was 72% +/- 5% and 45%
      +/- 6%, respectively. Those patients who survived attained a good quality of
      life. No factors were significantly associated with prolonged survival.

PMID- 9620459
TI  - Repair of postinfarction ventricular septal defects.
AB  - Postinfarction ventricular septal defects complicate approximately 1% to 2% of
      cases of acute myocardial infarction and account for about 5% of early deaths
      after myocardial infarction. By differentiating the surgical treatment of these
      acquired lesions from the surgical approaches used to repair congenital
      ventricular septal defects and realizing the significance of differing anatomic
      locations of postinfarction ventricular septal defects, techniques have been
      developed that have improved salvage of patients suffering this catastrophic
      complication of myocardial infarction. The principles underlying these surgical
      techniques include (1) expeditious establishment of total cardiopulmonary bypass
      with moderate hypothermia and meticulous attention to myocardial protection; (2)
      transinfarct approach to ventricular septal defect with the site of
      ventriculotomy determined by the location of the transmural infarction; (3)
      thorough trimming of the left ventricular margins of the infarct back to viable
      muscle to prevent delayed rupture of the closure; (4) conservative trimming of
      the right ventricular muscle as required for complete visualization of the
      margins of the defect; (5) inspection of the left ventricular papillary muscles
      and concomitant replacement of the mitral valve only if there is frank papillary
      muscular rupture; (6) closure of the septal defect without tension, which in most
      instances will require the use of prosthetic material; (7) closure of the
      infarctectomy without tension with generous use of prosthetic material as
      indicated, and epicardial placement of the patch to the free wall to avoid strain
      on the friable endocardial tissue; and (8) buttressing of the suture lines with
      pledgets or strips of Teflon felt or similar material to prevent sutures from
      cutting through friable muscle.

PMID- 9620460
TI  - Transcatheter management of ventricular septal rupture after myocardial
      infarction.
AB  - Despite improvements in surgical management of ventricular septal rupture (VSR)
      after myocardial infarction (MI), perioperative risk may be excessive for
      particular patients. Our experience with transcatheter closure of congenital
      ventricular septal defects led to our transcatheter attempts to close VSR after
      MI in patients without prior surgical repair who were thought to have prohibitive
      surgical risk (7), or similarly ill patients who had residual shunting after
      attempted surgical VSR closure (11). Of the 11 patients with postoperative
      residual patch-margin defects, survival (median 54 months) has not been limited
      by procedural success in any. Of the 7 patients without prior surgical repair,
      survival past hospitalization or to the present occurred in 3 patients, all of
      whom presented months after initial VSR. All survivors are in NYHA class II. Our
      experience suggests that optimal management of patients with post MI-VSR requires
      surgical-medical collaboration that extends surgical success to highest risk
      patients via catheter-based therapeutics.

PMID- 9620461
TI  - Lung transplantation for pulmonary hypertension: patient selection and
      maintenance therapy while awaiting transplantation.
AB  - Although lung transplantation is considered a definitive treatment of patients
      with advanced pulmonary vascular disease and pulmonary hypertension, advances in
      the success of the medical management of patients with pulmonary hypertension
      make it less clear as to when to refer a patient for transplantation. Coumadin
      anticoagulation is associated with improved survival in all patients, and calcium
      channel blockers therapy with improved survival in very select patients. Chronic
      prostacyclin represents a newer therapy that seems to have a dramatic impact on
      patients' functional class and survival. As improvements continue in the medical
      management in pulmonary hypertension, and in survival of patients undergoing lung
      transplantation, the guidelines for patient selection should be constantly
      evolving.

PMID- 9620462
TI  - Controlling perioperative morbidity and mortality after lung transplantation for
      pulmonary hypertension.
AB  - Lung transplantation for pulmonary hypertension now accounts for more than 18% of
      all transplantations performed with 1-year survival rates for primary pulmonary
      hypertension approximating 65%. Patients have NYHA class III or IV symptoms and
      typically have marked right ventricular dysfunction. Accelerated or acute
      decompensation can occur. A decline in status leads to a patient with severe
      right heart failure, hepatic dysfunction and severe malnutrition, conditions that
      increase perioperative morbidity and mortality. Immediate right ventricular
      dysfunction may be related to allograft injury with persistent elevation of
      pulmonary artery pressures or to intrinsic right ventricular disease; this can be
      supported with inotropic medications. Single-lung transplantation results in
      postoperative physiology that can require aggressive therapy to limit mortality.
      When allograft dysfunction occurs, significant hypoxemia results to a greater
      degree than that observed with single-lung transplantations for other diseases or
      following double-lung transplantation. As a result, careful donor selection for a
      single lung transplantation is crucial. The most common reason for prolonged
      ventilation is allograft reperfusion injury with ventilation-perfusion
      mismatching. Neuromuscular blockade can decrease oxygen utilization and improve
      chest wall compliance, whereas lateral positioning with the native lung down can
      be crucial to improving V/Q matching. Differential lung ventilation allows the
      application of larger quantities of positive end-expiratory pressure to the
      injured allograft. The use of exogenous nitrates has been advocated to reduce
      pulmonary vascular resistance. Nitric oxide has attractive potential benefits
      because it can be delivered directly to the lungs and functions to dilate the
      pulmonary vascular bed. All else having failed, we and others have successfully
      used extracorporeal membrane oxygenation to support cardiopulmonary function.

PMID- 9620463
TI  - Lung transplantation and repair of complex congenital heart lesions in patients
      with pulmonary hypertension.
AB  - Pulmonary vascular disease in conjunction with either a previously repaired or an
      unrepaired congenital heart defect is the third most common indication for lung
      transplantation in the pediatric age range. Because scarcity of donor organs
      remains a critical issue and heart-lung donor blocks are becoming diminishingly
      available, efforts must be directed towards other options such as combining lung
      transplantation with correction of the underlying congenital heart defect.
      Certain defects like congenital pulmonary vein stenosis are eradicated by removal
      of the diseased lungs, whereas others such as complete atrioventricular canal and
      pulmonary atresia with ventricular septal defect require cardioplegic arrest of
      the heart and intracardiac repair in conjunction with the lung transplantation. A
      breakdown of this patient population into subgroups may be helpful both in
      thinking about the pathophysiology and in determining appropriate indications and
      timing of transplantation. Earlier studies from our center showed the high-risk
      nature and formidable undertaking of caring for this complex group of patients.
      Through continued experience, there has been gradual improvement in early
      outcomes. As with all other groups of lung transplantation patients, obliterative
      bronchiolitis remains the major deterrent to long-term survival.

PMID- 9620464
TI  - The impact of bronchiolitis obliterans on late morbidity and mortality after
      single and bilateral lung transplantation for pulmonary hypertension.
AB  - Primary pulmonary hypertension (PPH) is a rare cardiovascular disease with a
      variable course; however, in general, its prognosis is poor. Among the various
      treatment options available, transplantation (initially heart-lung
      transplantation, and later isolated single or bilateral lung transplantation) has
      become an accepted modality. Heart-lung transplantation is necessary only in a
      minority of patients because right ventricular recovery has been gratifying after
      isolated lung transplantation. Furthermore, the scarcity of suitable donor organs
      mandates the achievement of the maximal number of heart and lung transplants from
      the limited donor pool. Available published data show that both single and
      bilateral lung transplantation are suitable alternatives for the majority of
      patients with pulmonary hypertension. Bronchiolitis obliterans syndrome (BOS),
      the main cause of late mortality and morbidity in lung transplant recipients,
      affects pulmonary hypertensive patients as it does other recipient subgroups. The
      available data regarding the impact of BOS on single versus bilateral lung
      recipients with pulmonary hypertension are somewhat scanty. Although some have
      suggested that BOS is more prevalent among PPH recipients, this is not uniformly
      supported through the literature. Other reports have documented severe
      ventilation-perfusion imbalance associated with graft dysfunction secondary to
      BOS in single lung transplant recipients with PPH. Despite this, there are no
      available data to document a significant survival benefit for PPH patients
      receiving bilateral versus single lung transplantation. Our own transplantation
      experience at Washington University in St. Louis with pulmonary hypertension
      shows a trend toward better survival in bilateral lung recipients, although this
      difference is not significant. Ultimately, both single and bilateral lung
      replacement seem to be satisfactory transplant options in PPH. Both recipient
      groups are affected by BOS, and longer follow-up of larger numbers of patients
      may document superior survival and functional outcome with bilateral lung
      replacement.

PMID- 9620466
TI  - Antibody-based spot test for NADH-cytochrome b5 reductase activity for the
      laboratory diagnosis of congenital methemoglobinemia.
AB  - NADH (reduced Coenzyme I)-cytochrome b5 reductase (b5R) is a multifunctional
      redox enzyme, whose deficiency causes recessive congenital methemoglobinemia. A
      novel procedure for the detection of b5R activity in human hemolysates was
      developed, in which b5R monoclonal antibodies dot-blotted on nitrocellulose
      membrane was used to capture and enrich b5R from hemolysates, and the captured
      b5R activity was subsequently visualized with the substrate 3-(4,5
      dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide. Application of this simple
      method to the detection of b5R activity in the hemolysates from different
      subjects demonstrated that it was both sensitive and reliable. Our method would
      be useful for the laboratory diagnosis of congenital methemoglobinemia.

PMID- 9620465
TI  - Determination of alpha-amylase using 4-O-beta-D-galactopyranosylmaltotetraose
      (Gal-G4) as a substrate.
AB  - A new substrate, 4-O-beta-D-galactopyranosylmaltotetraose (Gal-G4) is applied for
      the determination of alpha-amylase in serum and urine in a coupled assay with
      alpha-glucosidase (EC 3.2.1.20), glucokinase (EC 2.7.1.2) and glucose-6-phosphate
      dehydrogenase (EC 1.1.1.49) as auxiliary enzymes. Gal-G4 having a 4-position of
      the non-reducing-end glucose residue modified by a beta-galactopyranose group is
      resistant for degradation by alpha-glucosidase as auxiliary enzyme. Moreover,
      this substrate is hydrolyzed at just one position by alpha-amylase in serum and
      urine. More than 99% of the products generated from Gal-G4 by alpha-amylase are
      identified 4-O-beta-D-galactopyranosylmaltose (Gal-G2), maltose, respectively.
      Glucose and maltose do not interfere the value of alpha-amylase activity at least
      up to 0.056 mmol/l (1 g/dl) glucose and 0.027 mmol/l (1 g/dl) maltose,
      respectively. We are now carrying out this work under the authority of The Enzyme
      committee of Japanese Society of Clinical Chemistry (JSCC) as a standard method
      for determination of alpha-amylase in clinical chemistry.

PMID- 9620467
TI  - Comparison of four commercial urinary albumin (microalbumin) methods:
      implications for detecting diabetic nephropathy using random urine specimens.
AB  - The results of four urinary albumin methods used to identify patients with early
      diabetic renal disease were compared using random urine samples from healthy and
      diabetic patients. These methods were the Beckman Array and Behring BNAI
      immunonephelometric methods, the Dade aca particle-enhanced turbidimetric
      inhibition immunoassay method, and the INCSTAR SPQ immunoturbidimetric method.
      The albumin/creatinine ratio reference interval was found to be 2-20 mg albumin/g
      creatinine (mg/g) for the Array and 3.5-27.5 mg/g for the aca method. All four
      methods were compared using urines from a group of diabetic and nondiabetic
      patients. The BNAI, SPQ and Array methods compared well with one another while
      the aca demonstrated a positive bias of almost 60% at the 30 mg/g and 300 mg/g
      levels with certain lots of reagent and calibrator. Calibrator cross-over
      experiments demonstrated that some of the positive bias of the aca method could
      be accounted for by calibrator differences.

PMID- 9620468
TI  - Correlation between serum cytokeratin 19 fragment and tissue polypeptide antigen
      levels in patients with non-malignant diseases.
AB  - It has been reported that cytokeratin 19 fragment (CYFRA 21-1) is superior to
      tissue polypeptide antigen (TPA) as a tumor marker, although there is a high
      correlation between CYFRA 21-1 and TPA levels in patients with lung cancer. We
      investigated correlations between these tumor markers in patients with non
      malignant diseases. Marked correlations were found between CYFRA 21-1 and TPA
      levels in healthy subjects (n = 31), non-insulin-dependent diabetes mellitus (n =
      160) and hemodialysis patients (n = 83) (range of r-value = 0.90-0.93, P <
      0.0001). However in liver cirrhosis patients (n = 36), only a weak correlation
      was found (r = 0.39, P < 0.0001) and there were correlations between only TPA and
      both aspartate aminotransferase and alanine aminotransferase levels (r2 = 0.48
      and 0.36, P < 0.0001). The elevated TPA levels in liver cirrhosis patients may be
      related to the decreased specificity of TPA as a tumor marker.

PMID- 9620469
TI  - Solubility of NH3 and apparent pK of NH4+ in human plasma, isotonic salt
      solutions and water at 37 degrees C.
AB  - The solubility of ammonia, alphaNH3 (mM/mmHg), was determined at 37 degrees C and
      low ammonia partial pressure (0.02-1 mmHg) in pure water (n =24) as 46.70+/-0.40;
      aqueous isotonic salt solutions (n = 7) as 46.8+/-0.81; and human plasma (n = 5)
      as 42.0+/-0.66. The last figure increases to 45.3+/-0.63 if expressed in molal
      units (mmol/kg plasma water x mmHg) instead of molarity with respect to the water
      content of the plasma (mean from four healthy and fasting donors: 0.908+0.005 kg
      H2O/kg plasma; mean density at 37 degrees C: 1.020+/-0.002 kg/l). In pure water,
      the solubility value is the mean of three different methods: (a) extrapolation of
      the salting-out effect of ammonia in aqueous NaOH to zero concentration; (b)
      slope of Henry-Dalton's law and (c) directly measured in pure water and 0.001 M
      aqueous NaOH. Based on the Henderson-Hasselbalch equation for the system NH4/NH3
      in isotonic salt solutions and human plasma, both constants, apparent pK and
      solubility, can be derived from total ammonia concentration and pH at equilibrium
      with defined ammonia gas phase, if additionally the concentration of NH4 or NH3
      is known. This was verified, in the first case, by determining the concentration
      of NH4+ by the experimental conditions, and in the second, by two measurements of
      total ammonia concentration at two different pH values. Total ammonia
      concentration was measured by a specific enzymatic standard test and pH with the
      glass electrode. The mean apparent pK was 8.968+/-0.013 in isotonic salt
      solutions (n = 7), and in human plasma (n = 10) it was 9.014+/-0.033.

PMID- 9620470
TI  - An indirect method for urinary oxalate estimation.
AB  - Oxalate was first coprecipitated at pH 5 as calcium oxalate precipitate (COP)
      with excess calcium ions and ethanol. Interference in the COP, mainly calcium
      phosphate, was successfully removed by washing with 0.1 M acetic acid
      equilibrated with calcium oxalate monohydrate crystal. Since the calcium content
      of the washed COP showed a high correlation with the original oxalate
      concentration, both in artificial (r = 0.998, P <0.001) and real (r = 0.951, P <
      0.001 for colorimetric; r = 0.982, p < 0.001 for enzymatic methods) urines, it
      could be used to predict indirectly the urinary oxalate concentration. The mean
      percentage recovery of the predicted oxalate was 98.95, S.D. = +/-4.77% (n = 6).
      The method is simple, reproducible and relatively precise. It therefore could be
      set up as a routine method of urinary oxalate assessment in general clinical
      laboratories.

PMID- 9620471
TI  - Does uremia interfere with HbA1c results in the FPLC method with Mono S cation
      exchanger?
AB  - To study the effect of uremia on hemoglobin A1c determination by the Mono S FPLC
      method, samples from uremic patients, with and without diabetes, and controls,
      were analysed with a modified chromatography with enhanced resolution. Besides
      specific HbA1c, four minor peaks could be seen, included in routine HbA1c values.
      Two of these differed in concentration in the patient groups studied: a shoulder
      like peak close to the specific HbA1c (S fraction) and a slightly less cationic
      minor peak (M fraction). Both S and M peaks were higher in uremic than in
      nonuremic subjects, but the M peak was associated more with diabetes. In the
      nondiabetic group, the mean routine HbA1c value was 0.8% units higher in uremic
      than nonuremic individuals. The specific HbA1c was nondependent on uremia. Thus,
      in uremic patients, there seems to be falsely elevated HbA1c values, mainly
      because of small interfering hemoglobin fractions, not specific HbA1c.

PMID- 9620472
TI  - Development of an affinity-column-mediated enzyme-linked immunosorbent assay for
      ferritin.

PMID- 9620473
TI  - An automated procedure for the determination of protein concentration in
      subcellular fractions.

PMID- 9620474
TI  - Lipid peroxidation and antioxidants in oral squamous cell carcinoma.

PMID- 9620475
TI  - Standardized determination of apolipoprotein E phenotypes by simplified
      isoelectric focusing/immunoblotting in plasma and synovial fluid.

PMID- 9620476
TI  - Botanical dermatology.

PMID- 9620477
TI  - Salicylic acid revisited.

PMID- 9620478
TI  - Xanthelasma palpebrarum and risk of atherosclerosis.

PMID- 9620479
TI  - Glucocorticoid-induced osteoporosis.

PMID- 9620480
TI  - Clarithromycin: a new perspective in rosacea treatment.

PMID- 9620481
TI  - Immunoregulatory mechanisms and stress hormones in psoriasis (part 1)
AB  - BACKGROUND: In an earlier paper, the author noted that psoriatic eruptions may be
      produced in phases of humoral and cellular immunodeficiency and in the presence
      of streptococcal antigen-releasing inflammatory foci. In this study it was
      investigated as to whether stress hormones glucocorticoids, catecholamines) are
      substantially involved in the activity phases (eruptions) of psoriasis. METHODS:
      During a series of investigations over two years, the following were determined
      for 70 chronic psoriasis patients and 50 controls: cortisol-adrenaline serum
      levels, polyclonal serum immunoglobulins IgM, IgG, IgA, total serum IgE,
      complements C3, C4, T-cells and subpopulations, streptococcal antibody titres
      ASO/ADNase B. RESULTS: Phases of clinical inactivity are associated with a
      mechanism called immunologic regulation: elevated antibacterial titres and
      unremarkable findings for all other parameters. Phases of clinical activity (in
      25/70 patient) showed absolutely elevated serum cortisol levels, absolutely
      decreased serum epinephrine levels, deficient serum IgM or IgG and IgE levels,
      increased C3, decreased C4 and T4:T8 ratio, and significantly elevated
      streptococcal titres. CONCLUSIONS: The greatly elevated serum cortisol levels
      indicate that glucocorticoids are produced in excess via the pituitary adrenal
      axis and are significantly involved in the triggering of immunosuppressive phases
      (eruptions) in psoriasis.

PMID- 9620482
TI  - Occupational protein contact dermatitis caused by meat and fish.
AB  - BACKGROUND: Protein contact dermatitis is a form of contact dermatitis possibly
      triggered by proteinaceous allergens. MATERIALS AND METHODS: We report two
      patients with a history of erythematous and urticarial skin reactions followed by
      transformation into prolonged papular symptoms upon contact with proteinaceous
      material. RESULTS: The symptoms reported by the patients were reproducible by
      skin testing with meat (cow) and fish (salmon). Both patients experienced
      extracutaneous manifestations after ingestion of meat and fish, as proven by oral
      challenge. Specific immunoglobulin E (IgE) antibodies were detected in the
      patients' blood. CONCLUSIONS: Both cases meet all major criteria of protein
      contact dermatitis, suggesting IgE-mediated immediate-type hypersensitivity with
      late-phase cutaneous reactions.

PMID- 9620483
TI  - Panniculitis in tuberculosis: a clinicopathologic study of nodular panniculitis
      associated with tuberculosis.
AB  - BACKGROUND: Certain types of panniculitis, erythema induratum of Bazin and
      erythema nodosum, have been well documented as tuberculids. Many histopathologic
      diagnoses of panniculitis have been reported in tuberculosis patients. This study
      investigates the correlation between underlying tuberculosis and
      clinicopathologic findings of panniculitis. METHODS: We retrospectively reviewed
      the clinical files of histologic-proven panniculitis cases at the Dermatologic
      Clinic, Siriraj Hospital from January 1992 to December 1995; only cases with
      active tuberculous foci were analyzed. RESULTS: The incidence of panniculitis
      caused by tuberculosis was 8.2%. The ratio of men to women was 1:1. The mean age
      of onset was 35.3 years. The average duration of the nodules was 35.5 days. There
      was a history of contact tuberculosis in 16.6%. Constitutional symptoms and a
      strongly positive purified protein derivative (PPD) reaction were found in 66.6%.
      Chest roentgenograms were abnormal in 83.3%. The erythrocyte sedimentation rate
      was elevated in all tested cases. The histopathologic diagnoses were nodular
      vasculitis (33.3%), erythema nodosum (50%), and cutaneous periarteritis nodosa
      (16.4%). The panniculitis lesion responded to standard antituberculous regimens
      in 4.6 weeks, on average, with residual hyperpigmentation. CONCLUSIONS: In
      panniculitis patients, clues for the investigation of tuberculosis included
      constitutional symptoms, elevated erythrocyte sedimentation rate, and abnormal
      chest roentgenograms. Histopathologic changes of panniculitis did not seem to
      correlate with underlying tuberculosis. The clinician should be aware of the
      tuberculosis, however, and should carefully search for active foci in all
      panniculitis patients.

PMID- 9620484
TI  - Successful prenatal exclusion of an unspecified subtype of severe epidermolysis
      bullosa.
AB  - BACKGROUND: In most cases of prenatal diagnosis of epidermolysis bullosa (EB),
      the subtype of severe EB from which the fetus is at risk is identified by
      studying the specimens of the proband. In this study, the parents of a child with
      an unspecified subtype of severe EB sought prenatal diagnosis for their second
      and third pregnancies. METHODS: The firstborn of a couple (the proband) suffered
      generalized blistering and erosions of the skin present from delivery, and died
      on the 11th postnatal day of severe EB of an unspecified type. The only
      diagnostic specimen available from the first infant was a conventionally stained
      skin section for light microscopy that showed the dermo-epidermal separation. For
      prenatal diagnosis in the second and third pregnancies, fetal skin biopsies were
      performed at 19 weeks of gestation. RESULTS: In both cases, fetal skin showed no
      ultrastructural abnormalities and no evidence of dermo-epidermal separation.
      Indirect immunofluorescence was positive for monoclonal antibodies against type
      VII collagen, laminin 5, uncein, alpha6 and beta4 integrins, BPAG2, and
      HD1/plectin, which are known to be reduced or absent in specific subsets of
      severe EB. The pregnancies were therefore continued, and normal healthy second
      and third children were delivered. CONCLUSIONS: Fetal skin biopsy, together with
      a panel of newly developed monoclonal antibodies, provided reliable prenatal
      diagnosis in the present family in which preliminary information of the EB
      proband was limited.

PMID- 9620485
TI  - Community health workers reduce skin diseases in East African children.
AB  - BACKGROUND: Epidemiologic data concerning skin diseases in many rural areas in
      sub-Saharan Africa are not available. Little is known about the effect of regular
      treatment schedules by paramedical staff (especially community health workers) in
      the primary healthcare system on the severity and prevalence of dermatoses.
      METHODS: 5780 school and pre-school children from 13 primary schools in four
      sublocations in rural western Kenya (Kisumu District) were examined for
      dermatoses by the author, together with community health workers in 1993. On-the
      spot training and weekend seminars about important and common dermatoses were
      also given. In 1994 a dermatology program was started within the primary
      healthcare system. Twelve trained community health workers carried out regular
      school visits once a week and diagnosed and treated pupils with dermatoses.
      Treatment was performed with gentian violet 1% solution for bacterial skin
      infections, Whitfield's ointment for dermatophytoses, benzylbenzoate emulsion 25%
      for scabies, and hydrocortisone acetate 1% cream for eczemas. All schools were
      visited again in 1995 to evaluate the long-term effects of the program. RESULTS:
      In 1993, the prevalence rate for dermatoses was 32.4%. Most of the skin diseases
      found were of infective origin (27.1% were caused by bacteria, 21.6% by fungi,
      and 17.6% by arthropods, mainly scabies mites). Dermatitis accounted for 3.5%. In
      1995, the prevalence of dermatoses declined to 29.6% (p<0.05), and this reduction
      was most strongly observed for tropical ulcers and tinea capitis. Additionally,
      there was an improvement in the extent and severity of skin diseases.
      CONCLUSIONS: This study defines, for the first time, the number and extent of
      skin diseases in children in rural Kisumu District; most dermatoses were of
      infective origin. The study demonstrates that community health workers in the
      primary healthcare system are capable of dealing successfully with the most
      common dermatoses in children following a short training period.

PMID- 9620486
TI  - Atypical molluscum contagiosum infection in an HIV-infected patient.

PMID- 9620487
TI  - Bubble hair--a possible explanation for its distribution.

PMID- 9620488
TI  - Reactive angioendotheliomatosis with underlying hepatopathy and hypertensive
      portal gastropathy.

PMID- 9620489
TI  - Stripped skin model to predict irritation potential of topical agents in vivo in
      humans.
AB  - BACKGROUND AND OBJECTIVE: The prediction of the irritation effects of products of
      low irritation potential remains problematic. An in vivo human model was utilized
      to define the irritation potential of a topical agent after partial removal of
      the stratum corneum by cellophane tape stripping. METHODS: The tape was applied
      to and removed approximately 50 times (mean, 50.0 +/- 16.7) from each test site
      on the volar aspect of the forearm. One site served as the stripping control,
      receiving tape stripping only. The other test sites received the topical agent
      and placebo control. Transepidermal water loss (TEWL) was measured before and
      daily for 5 days. The TEWL values at baseline after stripping represented the
      point of maximal stripping barrier disruption. The barrier disruption and
      irritation potential were assessed with TEWL measurements. RESULTS: The results
      showed that the model topical agent had no adverse effect on barrier repair, i.e.
      did not interfere with TEWL normalization. CONCLUSIONS: This model provides a
      method for the prediction, with exaggerated sensitivity, of chemical irritation
      and proclivity to enhance or retard water barrier repair. We believe that the
      model may predict the response of low irritation materials and may be more
      sensitive than patch testing on normal skin, particularly for products to be used
      on certain areas, e.g. the face, anus, etc., or even mucous membranes. The model
      must receive extensive use with chemicals of varying properties in order to
      define its chemical relevance.

PMID- 9620490
TI  - The effects of cadexomer iodine paste in the treatment of venous leg ulcers
      compared with hydrocolloid dressing and paraffin gauze dressing. Cadexomer Iodine
      Study Group.
AB  - BACKGROUND: The aim was to examine cadexomer iodine paste in a comparative
      clinical trial. METHODS: A 12-week, randomized, open, controlled, multicenter,
      multinational trial in patients with exudating, venous leg ulcers of cadexomer
      iodine paste (Iodosorb/Iodoflex), hydrocolloid dressing (Duoderm E, Granuflex E),
      or paraffin gauze dressing (Jelonet) was carried out. All patients used short
      stretch compression bandages (Comprilan) throughout the study. The primary
      efficacy variable was a reduction in ulcer size (%), and the secondary end-point
      was the time taken to stop exudation, when the patient had completed the study
      according to the protocol. A total of 153 patients entered the study and were
      treated for 12 weeks or until cessation of exudation. RESULTS: The mean reduction
      in ulcer size in all patients was 62% with cadexomer iodine vs. 41% and 24% for
      hydrocolloid and paraffin gauze (ns). Of those treated for 12 weeks (n = 51),
      ulcer area reduction was 66% for cadexomer iodine and 18% for hydrocolloid (p =
      0.0127). For the whole material, the rate of healing (ulcer area reduction per
      week) was significantly higher for cadexomer iodine than for paraffin gauze (0.64
      cm2/week vs. 0.19 cm2/week, p = 0.0353). The treatment costs were similar in all
      groups; however, when the costs were correlated with healing over a 12-week
      period, cadexomer iodine paste was found to be more cost effective than
      hydrocolloid dressing or paraffin gauze dressing. CONCLUSIONS: This study shows
      that cadexomer iodine paste is an efficient, cost-effective and safe alternative
      to hydrocolloid dressing and paraffin gauze dressing for the treatment of venous
      leg ulcers.

PMID- 9620491
TI  - Stasis dermatitis--a new cutaneous manifestation of Budd-Chiari syndrome.

PMID- 9620492
TI  - Complete remission of recalcitrant polyarteritis nodosa after combination
      chemotherapy for accompanying B-cell non-Hodgkin lymphoma.

PMID- 9620493
TI  - Eccrine poroma associated with Bowen's disease.

PMID- 9620494
TI  - Spinal and epidural blockade and perioperative low molecular weight heparin:
      smooth sailing on the Titanic.

PMID- 9620495
TI  - Patient simulator competency testing: ready for takeoff?

PMID- 9620496
TI  - Testing internal consistency and construct validity during evaluation of
      performance in a patient simulator.
AB  - The primary goal of this study was to test the items in a rating system developed
      to evaluate anesthesiologists' performance in a simulated patient environment. A
      secondary goal was to determine whether the test scores could discriminate
      between resident and staff anesthesiologists. Two 5-item clinical scenarios
      included patient evaluation and induction and maintenance of anesthesia. Rating
      scales were no response to the problem (score = 0), compensating intervention
      (score = 1), and corrective treatment (score = 2). Internal consistency was
      estimated using Cronbach's coefficient alpha. Scores between groups were compared
      using the Cochran-Mantel-Haenszel test. Subjects consisted of 8 anesthesiology
      residents and 17 university clinical faculty. The Cronbach's coefficient alpha
      was 0.27 for Scenario A and 0.28 for Scenario B. Two items in each scenario
      markedly decreased internal consistency. When these four items were eliminated,
      Cronbach's coefficient alpha for the remaining six items was 0.66. Faculty
      anesthesiologists scored higher than residents on all six items (P < 0.001). A
      patient simulator-based evaluation process with acceptable reliability was
      developed. IMPLICATIONS: The reliability of anesthesia clinical performance in a
      patient simulation environment was assessed in this study. Of 10 items, 4 were
      poor in the evaluation process. When these items were removed, the reliability of
      the instrument improved to a level consistent with other studies. Because faculty
      scored higher than resident anesthesiologists, the instrument also showed
      discriminant validity.

PMID- 9620497
TI  - The influence of an aging surgical population on the anesthesia workload: a ten
      year survey.
AB  - To assess the evolution of the anesthetic workload related to elderly population
      (> or = 65 yr) at the University Hospital of Geneva, the total number of
      anesthesia cases, high-risk patients, and emergency procedures, as well as the
      total duration of anesthesia and incidence of perianesthetic complications, were
      retrospectively analyzed over 10 yr. The squared correlation coefficient was used
      to assess the proportion of variance explained by the linear regression of the
      absolute and the relative number of events over time. More than 165,000
      anesthesia procedures were analyzed, and the data were separated into two groups:
      the younger population (<65 yr) and the elderly population (> or = 65 yr). From
      1985 to 1994, the elderly surgical population grew significantly faster (P <
      0.001) than the elderly resident population (from 20.3% to 25.1% versus from
      12.5% to 13.6%). Half of the increased number of anesthesia cases during this
      period were administered to elderly patients. The number of high-risk elderly
      patients increased by 48.3% (P < 0.0001). The number of emergency procedures in
      elderly patients increased only until 1991, and a significant decrease in the
      incidence of perianesthetic complications was observed. Because the mean duration
      of each procedure remained constant, the increased anesthetic workload in our
      institution was mainly due to increased geriatric surgical activity.
      IMPLICATIONS: During a study period of 10 yr, the increased anesthetic workload
      (defined as the number of anesthesia cases, high-risk patients, emergency
      procedures, and complication rate) at the University Hospital of Geneva was
      mainly due to the increased geriatric (patients > or = 65 yr) surgical activity,
      not to the aging of the resident population.

PMID- 9620498
TI  - Unplanned tracheal extubation outside the operating room: a quality improvement
      audit of hemodynamic and tracheal airway complications associated with emergency
      tracheal reintubation.
AB  - The incidence of hemodynamic and airway complications associated with tracheal
      reintubation after an unplanned extubation has not been established. Patients
      whose tracheas were emergently intubated outside the operating room were reviewed
      over a 27-mo period via a quality improvement vehicle to evaluate hemodynamic and
      airway complications. Data from a subset of patients (n = 57) who underwent
      tracheal reintubation after unplanned (self-) extubation were collected for
      analysis. Of the reintubations, 93% took place within 2 h of self-extubation. Of
      the patients, 72% had hemodynamic alterations and/or airway-related
      complications, including hypotension (35%), tachycardia (30%), hypertension
      (14%), multiple laryngoscopic attempts (22%), difficult laryngoscopy (16%),
      difficult intubations (14%), hypoxemia (14%), and esophageal intubation (14%). In
      addition, one surgical airway and one case of "cannot ventilate, cannot intubate"
      leading to cardiac arrest and death were recorded. These findings suggest that
      patients requiring reintubation will likely do so soon after self-extubation and
      that reintubation can be fraught with significant hemodynamic and airway
      complications. Less than one third of patients undergo a mishap-free
      reintubation. Strategies to decrease the self-extubation rate in the intensive
      care unit are needed to improve patient safety and to lessen the potential impact
      of emergency airway management. IMPLICATIONS: Self-extubation by patients
      requiring mechanical ventilation can be life-threatening, and replacing the
      breathing tube often leads to hemodynamic and airway complications. Using this
      quality improvement audit, 57 self-extubating patients and the complications
      associated with replacing the breathing tube, which are numerous and can lead to
      significant morbidity and mortality, were analyzed.

PMID- 9620499
TI  - Influences of cardiopulmonary bypass and fentanyl anesthesia on hepatic
      circulation and oxygen metabolism in beagles.
AB  - Decreases in hepatic blood flow (HBF) have been reported in patients and in
      animal experiments during cardiopulmonary bypass (CPB). We examined changes in
      HBF and hepatic oxygen metabolism during CPB in 16 beagles anesthetized with
      fentanyl. Hepatic arterial blood flow (HABF) and portal venous blood flow (PVBF)
      were measured by using an electromagnetic flowmeter before and during
      normothermic and hypothermic CPB with 10 microg x kg(-1) x h(-1) (F-10 group; n =
      8) or 50 microg x kg(-1) x h(-1) (F-50 group; n = 8) of fentanyl anesthesia. CPB
      was conducted with membrane oxygenation and a nonpulsatile pump flow of 2.4 L x
      m(-2) x min(-1). Hepatic oxygen delivery (HDO2) and consumption (HVO2) were
      calculated from HBF and oxygen content in arterial, portal venous, and hepatic
      venous blood. HABF did not change during normothermic CPB in the F-10 group, but
      it decreased significantly during hypothermic CPB in both groups, especially the
      F-50 group. During CPB, PVBF and total HBF decreased significantly in both groups
      more so with the larger dose of fentanyl--whereas HDO2 decreased significantly
      because the arterial and portal venous blood oxygen levels decreased. The HVO2
      was stable in the F-10 group but was significantly depressed during CPB in the F
      50 group. Our results indicate that during hypothermic nonpulsatile CPB larger
      doses of fentanyl are associated with reduced HBF and impaired HDO2 and HVO2.
      IMPLICATIONS: Hepatic dysfunction after cardiopulmonary bypass (CPB) has been
      frequently reported and could be partly attributed to hepatic circulatory
      disturbance during CPB. We found that, in beagles, large doses of fentanyl were
      associated with greater decreases in hepatic blood flow and hepatic oxygen
      metabolism during hypothermic CPB than smaller doses of fentanyl.

PMID- 9620500
TI  - Conjugated estrogen reduces transfusion and coagulation factor requirements in
      orthotopic liver transplantation.
AB  - We conducted a prospective, randomized study to determine the efficacy of
      conjugated estrogen in reducing blood product transfusion during orthotopic liver
      transplantation (OLT). Patients undergoing OLT were included in the study. Only
      those having a reaction time of more than 30 mm or 15 min (19 -28 mm) on computed
      thromboelastography (CTEG) at the beginning of surgery were enrolled in the
      study. Patients were randomized to receive either conjugated estrogen (CE) or
      placebo. Every patient received a first dose of CE (100 mg i.v.) (20 mL) or
      placebo (20 mL of isotonic sodium chloride solution) at the beginning of the
      procedure and a second dose of CE (100 mg i.v.) or 20 mL of placebo (20 mL of
      isotonic sodium chloride solution) just after reperfusion of the new graft. The
      two groups were similar in age, weight, requirement for veno-veno bypass, time on
      veno-veno bypass, CTEG measurement, and preoperative hemoglobin and platelet
      values. Blood products were given in relation to hematocrit and coagulation
      (CTEG) variables, which were measured every hour during the surgery. The amount
      of transfused blood products did not differ in terms of units of cryoprecipitate,
      but the intraoperative requirements for red blood cells (6 +/- 3 vs 9 +/- 6 U; P
      = 0.05), platelets (12 +/- 8 U vs 18 +/- 10 U; P = 0.05) and fresh-frozen plasma
      (3 +/- 3 U vs 6 +/- 4 U; P = 0.001) was significantly less in the estrogen group
      than in the control group. We conclude that CE is associated with a significant
      decrease in use of fresh-frozen plasma, platelets, and red blood cells during
      OLT. IMPLICATIONS: In this study, we prospectively investigated whether i.v.
      conjugated estrogen could decrease blood product transfusion during orthotopic
      liver transplantation. Conjugated estrogen-treated patients received less fresh
      frozen plasma, red blood cells, and platelets. In this population of patients,
      conjugated estrogen can be a useful addition in coagulation management during
      orthotopic liver transplantation.

PMID- 9620501
TI  - The effects of thyroid hormone modulation on rat liver injury associated with
      ischemia-reperfusion and cold storage.
AB  - We investigated the effects of thyroid hormone modulation on liver injury
      associated with ischemia-reperfusion (I-R) and cold storage in rats. First,
      euthyroid and thyroxine (T4)-pretreated rats were exposed in vivo to 20-min
      global liver ischemia, then 30-min reperfusion. Liver injury was assessed by
      measuring serum alanine aminotransferase (ALT) levels. Liver concentrations of
      adenine nucleotides, reduced glutathione (GSH), and oxidized glutathione were
      evaluated. Second, rats were given the antithyroid drug propylthiouracil (PTU).
      Livers stored at 0-1 degrees C in Euro-Collins' solution for 20 h were reperfused
      at 37 degrees C for 15 min. Lactate dehydrogenase (LDH) in the effluent perfusate
      and bile flow were evaluated during reperfusion. Serum ALT levels increased after
      ischemia and I-R. ALT increased significantly more in T4-pretreated than in
      euthyroid rats after ischemia and I-R. Preischemic levels of adenosine
      triphosphate (ATP) were significantly lower in livers from T4-pretreated than in
      euthyroid rats (6.22 +/- 0.7 and 11 +/- 0.9 nmol/mg protein, respectively; P <
      0.05). After ischemia, liver ATP was similarly reduced in T4-pretreated and
      euthyroid rats. After reperfusion, ATP partially recovered in euthyroid rats but
      remained low in T4-pretreated rats (6.7 +/- 1.0 and 1.91 +/- 0.7 nmol/mg protein,
      respectively; P < 0.05). Preischemic levels of liver GSH decreased to 44% in T4
      pretreated rats. After ischemia, GSH decreased similarly in euthyroid and T4
      pretreated rats. GSH recovered promptly after reperfusion in euthyroid rats but
      remained low in T4-pretreated rats (13.9 +/- 3.3 and 3.9 +/- 0.9 nmol/mg protein,
      respectively; P < 0.02). During reperfusion after cold storage, LDH in effluent
      perfusate was significantly lower and bile flow higher in livers from PTU
      pretreated rats than from euthyroid rats. The histopathological changes observed
      after I-R and cold storage confirmed the biochemical findings. Our results
      suggest that T4 administration exacerbates pretransplant liver damage by
      increasing liver susceptibility to I-R, whereas PTU administration reduces the
      liver injury associated with cold storage. IMPLICATIONS: We studied the effects
      of thyroid hormone modulation on liver injury associated with ischemia
      reperfusion and cold storage in rats. Thyroxine administration increased
      susceptibility to ischemia-reperfusion injury, whereas the antithyroid agent
      propylthiouracil reduced the deleterious effects associated with cold storage.

PMID- 9620502
TI  - The effects of intrinsic nitric oxide on cardiac neural regulation in cats.
AB  - In this study, we aimed to elucidate the effects of intrinsic nitric oxide (NO)
      on cardiac neural regulation. Twenty-two cats were anesthetized with 1.5%
      isoflurane and allocated to Group I (intact; n = 7), Group D (denervated
      baroreceptors and vagi; n = 8), or Group B (autonomic blockade with i.v.
      hexamethonium, propranolol, and atropine; n = 7). Cardiac sympathetic nerve
      activity (CSNA), mean arterial pressure (MAP), sinus heart rate (HR), and A-H and
      H-V intervals during pacing (150 bpm) were measured before and after i.v.
      administration of a NO synthase inhibitor, NG-nitro-L-arginine (L-NNA, 30 mg/kg)
      and after reversal with an excessive dose of L-arginine (300 mg/kg), before and
      during intermittent electrical stimulation of the posterior hypothalamus. L-NNA
      significantly increased MAP in Groups I and B, but not in Group D. L-NNA
      significantly decreased HR and lengthened A-H in Group I, but not in other
      groups. L-arginine further decreased HR and lengthened A-H unexpectedly. The
      reasons for these findings could not be determined in this study. L-NNA did not
      change CSNA. Hypothalamic stimulation did not potentiate L-NNA-induced changes in
      CSNA, hemodynamic variables, and atrioventricular conduction. In conclusion,
      intrinsic NO may modulate atrioventricular conduction and sinus rate through a
      vagal cholinergic, rather than a nonautonomic mechanism. IMPLICATIONS:
      Elucidating the roles of intrinsic nitric oxide (NO) on cardiac neural regulation
      is important. In intact, vagotomized, and baroreceptor-denervated or
      pharmacologically autonomic blockaded cats, an NO synthesis inhibitor was
      administered, and atrioventricular conduction and cardiac sympathetic neural
      discharge were measured. The results suggest a vagal cholinergic mechanism of
      intrinsic NO.

PMID- 9620503
TI  - The effects of propofol on cerebral blood flow velocity and cerebral oxygen
      extraction during cardiopulmonary bypass.
AB  - We investigated the effects of burst-suppression doses of propofol on cerebral
      blood flow velocity (CBFV), cerebral oxygen extraction (COE), and dynamic
      autoregulation in 20 patients undergoing cardiac surgery. The experimental
      procedure was performed during nonpulsatile cardiopulmonary bypass (CPB) with
      stable hypothermia (32 degrees C) in fentanyl-anesthetized patients. Middle
      cerebral artery transcranial Doppler flow velocity, right jugular bulb oxygen
      saturation, and jugular venous pressure (JVP) were continuously measured. Dynamic
      autoregulation was tested by stepwise changes in mean arterial pressure (MAP)
      within a range of 40-80 mm Hg by sodium nitroprusside and phenylephrine before
      (control) and during propofol infusion, with a stable plasma concentration
      (approximately 9 microg/mL). Propofol induced a 35% decrease in CBFV (P < 0.0001)
      and a 10% decrease in COE (P < 0.05) compared with control. The slopes of the
      curves relating CBFV and COE to cerebral perfusion pressure (CPP = MAP - JVP)
      were less pronounced with propofol (P < 0.01 and P < 0.05, respectively). We
      conclude that propofol decreases CBFV and improves dynamic autoregulation during
      moderate hypothermic CPB. Furthermore, during propofol infusion, cerebral blood
      flow was in excess relative to oxygen demand, as indicated by the decrease in
      COE. IMPLICATIONS: In this study, we evaluated the effects of propofol on
      continuously measured cerebral blood flow velocity (CBFV) and cerebral oxygen
      extraction as a function of perfusion pressure. Propofol induced 35% and 10%
      decreases in CBFV and cerebral oxygen extraction, respectively. The slope of the
      curve relating cerebral perfusion pressure to CBFV decreased with propofol.

PMID- 9620504
TI  - Vasopressin for the treatment of refractory hypotension after cardiopulmonary
      bypass.

PMID- 9620505
TI  - Ethylenediaminetetraacetic acid-dependent pseudothrombocytopenia in a cardiac
      surgical patient.

PMID- 9620506
TI  - A modified endotracheal tube for infants and small children undergoing video
      assisted thoracoscopic surgery.

PMID- 9620507
TI  - The effects of general versus epidural anesthesia for outpatient extracorporeal
      shock wave lithotripsy.
AB  - Although many anesthetic techniques are described for immersion extracorporeal
      shock wave lithotripsy (ESWL), regional and i.v. techniques are the most commonly
      reported. This randomized, prospective study compared general anesthesia (GA) and
      epidural anesthesia (EPID) with regard to effectiveness, side effects, induction
      time, and recovery in patients undergoing ESWL using an unmodified Dornier HM-3
      lithotriptor. Twenty-six healthy outpatients were randomized to GA (propofol,
      N2O, laryngeal mask airway) or EPID (lidocaine 1.5% with epinephrine).
      Intraoperative and postoperative supplemental medications, side effects, and
      complications were noted. Induction times and times required to meet standard
      recovery criteria were compared between groups. Patients were surveyed regarding
      their satisfaction with anesthesia. All patients in the EPID group had effective
      blocks with a single catheter insertion and local anesthetic injection. In the GA
      group, the LMA was inserted successfully in all patients. Time from room entry to
      procedure start was significantly less in the GA group (23 +/- 11 vs 34 +/- 9
      min; P < 0.05). Patients in the GA group were ready for discharge home earlier
      (127 +/- 59 vs 178 +/- 49 min; P < 0.05). Only three patients experienced nausea
      (one in the GA group, two in the EPID group). There were no differences in
      patient or urologist satisfaction with anesthesia. We conclude that GA is
      associated with a rapid recovery compared with EPID. IMPLICATIONS: General
      anesthesia with propofol, nitrous oxide, and a laryngeal mask airway is
      comparable to epidural anesthesia with lidocaine for outpatient extracorporeal
      shock wave lithotripsy procedures. However, early recovery is more rapid after
      general anesthesia compared with epidural anesthesia.

PMID- 9620508
TI  - Propofol versus midazolam: safety and efficacy for sedating the severe trauma
      patient.
AB  - Previous studies have compared sedation profiles with midazolam (Mz) and propofol
      (Pf), particularly in heterogeneous populations of patients. Decreases in blood
      pressure and heart rate have been reported after the administration of propofol.
      These side effects are potentially deleterious in severe trauma patients,
      particularly in patients with head trauma. To assess the safety and efficacy of
      Mz and Pf, alone or in combination, in the prolonged sedation of severe trauma
      patients, we designed a prospective, controlled, randomized, study. One hundred
      consecutively admitted trauma patients requiring mechanical ventilation and
      sedation for more than 48 h were studied. Patients were sedated according to
      three different protocols based on the continuous i.v. administration of Mz
      alone, Pf alone, and Mz in combination with Pf. All patients received morphine
      chloride. Safety and efficacy were assessed during the sedation and wake-up
      periods according to clinical and laboratory variables. Cerebral hemodynamics
      were also studied in patients with head trauma. Patients were sedated for 6.3 +/-
      4.0 days (mean +/- SD). All three sedation regimens were equally efficacious in
      achieving the desired sedation goal. The incidence of adverse events during the
      sedation period was also similar. In head trauma patients with intracranial
      pressure (ICP) monitoring, we did not find differences in ICP, cerebral perfusion
      pressure, or jugular venous oxygen saturation among the three groups. The serum
      triglyceride concentration was significantly higher in the Pf group. Wake-up time
      was significantly shorter in the Pf group. We conclude that both Mz and Pf are
      safe and efficacious in the sedation of severe trauma patients. The use of Pf in
      these patients is associated with a high incidence of hypertriglyceridemia and a
      shorter wake-up time. IMPLICATIONS: In a prospective, controlled, randomized
      study, we confirmed the safety and efficacy of midazolam and propofol, alone or
      in combination, in the prolonged sedation of a homogeneous group of severe trauma
      patients, particularly in patients with head trauma. The propofol group had
      shorter wake-up times and higher triglyceride levels.

PMID- 9620509
TI  - 0.45% saline and 5% dextrose in water, but not 0.9% saline or 5% dextrose in 0.9%
      saline, worsen brain edema two hours after closed head trauma in rats.
AB  - In this study, we examined the effect of four i.v. fluids (250 mL/kg) on blood
      glucose and osmolality and brain tissue specific gravity after closed head trauma
      (CHT) in rats. CHT was delivered at Time 0; blood was sampled at 60 min; fluid
      infusion began at 75 min and ended at 105 min. Blood was again sampled at 105 and
      120 min, and brain tissue specific gravity was determined at 120 min. Five groups
      (one control and four fluid-treated groups) received CHT, and five other groups
      (one control and four fluid-treated) did not (n = 9 in each group). 0.45% saline
      (1/2 NS) and 5% dextrose in water (D5W) accentuated the decrease of brain tissue
      specific gravity (1.0366 +/- 0.0025 and 1.0368 +/- 0.0028, respectively; mean +/-
      SD) caused by CHT (1.0395 +/- 0.0036), but 5% dextrose in 0.9% saline (D5NS) and
      0.9% saline (NS) did not (1.0431 +/- 0.0042 and 1.0389 +/- 0.0049, respectively).
      In addition, 1/2 NS decreased blood osmolality (248 +/- 6 mOsm/L), D5W increased
      blood glucose (1095 +/- 173 mg/dL), D5NS increased blood osmolality (350 +/- 5
      mOsm/L) and glucose (1695 +/- 76 mg/dL), and NS caused no significant change. We
      conclude that administering hypoosmolar i.v. fluids after CHT causes a
      significant worsening of cerebral edema 2 h after CHT. IMPLICATIONS: We
      previously reported worse neurological outcome and/or mortality after closed head
      trauma in rats when 5% dextrose in water or 0.45% saline was given i.v. compared
      with 0.9% saline or 5% dextrose in 0.9% saline. The present results and our
      previous findings indicate that worsening of outcome after closed head trauma in
      rats may be caused more by edema formation than by hyperglycemia.

PMID- 9620510
TI  - The effects of pentobarbital on blood-brain barrier disruption caused by
      intracarotid injection of hyperosmolar mannitol in rats.
AB  - This study was performed to evaluate both the effects of pentobarbital on
      disruption of the blood-brain barrier (BBB) by hyperosmolar mannitol and the
      relationship between its effect on blood pressure and the integrity of the BBB.
      Under isoflurane anesthesia, rats in the control group were infused with 25%
      mannitol into the internal carotid artery before measuring the transfer
      coefficient (Ki) of 14C alpha-aminoisobutyric acid. Ten minutes before the
      administration of mannitol, rats received an infusion of pentobarbital: 20 mg/kg
      in the small-dose group and 50 mg/kg in the large-dose group. In another group of
      animals (hydralazine group), hydralazine was administered to maintain the mean
      arterial blood pressure (MAP) at 65 mm Hg during the experimental period. The MAP
      of the control group (113 +/- 14 mm Hg) was significantly higher (P < 0.002) than
      that of the small-dose pentobarbital group (78 +/- 13 mm Hg) or the large-dose
      pentobarbital group (68 +/- 14 mm Hg). In the control group, the Ki of the cortex
      ipsilateral to the mannitol injection was increased to 4.5 times that of the
      contralateral cortex (14.5 +/- 7.7 vs 3.2 +/- 0.6 microL x g(-1) x min(-1); P <
      0.002). The Ki of the ipsilateral cortex of the small-dose pentobarbital group
      was 9.7 +/- 5.6 microL x g(-1) x min(-1). The Ki of the ipsilateral cortex of the
      large-dose pentobarbital group was 5.5 +/- 2.9 microL x g(-1) x min(-1), and
      lower (-9.0 microL x g(-1) x min(-1)) than that of the control animals (P <
      0.05). There was no significant difference in the Ki of the contralateral cortex
      among any of the three groups of animals. At the same MAP, the Ki of the
      ipsilateral cortex of the large-dose pentobarbital group was lower (-4.3 microL x
      g(-1) x min(-1)) than that of the hydralazine group (9.8 +/- 4.6 microL x g(-1) x
      min(-1)) (P < 0.05). Pentobarbital attenuated the BBB disruption induced by
      hyperosmolar mannitol. This may be attributed, at least in part, to the blood
      pressure effect of pentobarbital. IMPLICATIONS: When the blood-brain barrier
      (BBB) was disrupted by a hyperosmolar solution, pentobarbital attenuated the
      degree of leakage of the BBB. Systemic hypotension caused by pentobarbital played
      a significant role in decreasing the leakage. Our study suggests that when the
      BBB is disrupted, pentobarbital may be effective in protecting the BBB.
      Furthermore, systemic blood pressure plays an important role in determining the
      degree of disruption.

PMID- 9620511
TI  - Successful epidural anesthesia for cesarean section for sextuplets.

PMID- 9620512
TI  - Quantitative analysis of respiratory, motor, and sensory function after
      supraclavicular block.
AB  - The incidence and clinical significance of hemidiaphragmatic paresis after
      supraclavicular block of the brachial plexus is unknown. Eight healthy volunteers
      received a supraclavicular block with a standard technique using 30 mL of 1.5%
      lidocaine. Respiratory function was assessed with ultrasound of the diaphragm,
      respiratory inductive plethysmography (RIP), and pulmonary function tests (PFT)
      every 20 min. Sensory block was assessed with pinprick and motor block with
      isometric force dynamometry every 20 min. Four of eight subjects demonstrated
      hemidiaphragmatic paresis on both ultrasound and RIP. No subject experienced
      changes in PFT values or subjective symptoms of respiratory difficulty. Motor and
      sensory blockade outlasted hemidiaphragmatic paresis. These results are
      contrasted to the often symptomatic, 100% incidence of hemidiaphragmatic paresis
      seen after interscalene block. In this study of healthy volunteers,
      supraclavicular block was associated with a 50% incidence (95% confidence
      interval 14-86) of hemidiaphragmatic paresis that was not accompanied by clinical
      evidence of respiratory compromise. IMPLICATIONS: Interscalene block is always
      associated with diaphragmatic paralysis and respiratory compromise. The
      significance of these side effects after supraclavicular block is unknown. Using
      sensitive measures of respiratory function, we determined that diaphragmatic
      paralysis occurs less often with the supraclavicular approach and is not
      associated with respiratory difficulties in healthy subjects.

PMID- 9620513
TI  - Adding ketamine in a multimodal patient-controlled epidural regimen reduces
      postoperative pain and analgesic consumption.
AB  - We designed this double-blind study to evaluate the effect of adding small-dose
      ketamine in a multimodal regimen of postoperative patient-controlled epidural
      analgesia (PCEA). Ninety-one patients, ASA physical status I-III, undergoing
      major surgery, received a standardized general anesthesia and epidural
      catheterization in an appropriate intervertebral space after surgery. A PCEA
      device was programmed to deliver a regimen of morphine 0.02 mg/mL, bupivacaine
      0.8 mg/mL, and epinephrine 4 microg/mL, with the addition of ketamine 0.4 mg/mL
      (ketamine, n = 45) or without (control, n = 46). The mean visual analog pain
      scale (VAS) scores during cough or movement for the first 3 days after surgery
      were higher in the control group than in the ketamine group (P < 0.05), whereas
      the mean VAS score at rest for the first 2 days were higher in the control group
      than in the ketamine group (P < 0.05). Furthermore, patients in the control group
      consumed more multimodal analgesics than patients in the ketamine group for the
      first 2 days (P < 0.05). The sedation scores and the incidence of side effects
      (pruritus, nausea, emesis, sleep deprivation, motor block, and respiration
      depression) were similar between the two groups. We conclude that adding ketamine
      0.4 mg/mL in a multimodal PCEA regimen provides better postoperative pain relief
      and decreases consumption of analgesics. IMPLICATIONS: Many studies have
      evaluated one or a combination of two analgesics for postoperative pain control,
      but few have examined a multimodal approach using three or four different
      epidural analgesics. This study demonstrates an additive analgesic effect when
      ketamine is added to a multimodal analgesic treatment.

PMID- 9620514
TI  - Analgesic and cognitive effects of intravenous ketamine-alfentanil combinations
      versus either drug alone after intradermal capsaicin in normal subjects.
AB  - Combinations of opioids and N-methyl-D-aspartate (NMDA) antagonists enhance acute
      antinociception and reduce opioid tolerance in some animal experiments but have
      received little rigorous study in humans. To quantitatively assess the nature of
      the interaction of these two classes of drugs in producing analgesia and
      cognitive impairment, we compared i.v. infusions of ketamine, alfentanil, and
      ketamine-alfentanil combinations in 12 normal volunteers after an intradermal
      injection of capsaicin. Drug doses for a 70-kg subject in this six-session,
      randomized, double-blind, cross-over study were: ketamine 20 mg, ketamine 5 mg,
      alfentanil 2 mg, alfentanil 0.5 mg, ketamine 10 mg + alfentanil 1 mg, and
      ketamine 2.5 mg + alfentanil 0.25 mg, given over 35 min. Outcome measures were
      background pain, area and magnitude of hyperalgesia to pinprick, and cognitive
      performance on the Digit Symbol Substitution Test and the Perception Speed Test.
      The results demonstrated simple additivity for the effects of ketamine and
      alfentanil on pain, pinprick hyperalgesia, and cognitive impairment. We conclude
      that, at least in this experimental pain model, there is no clear advantage or
      disadvantage of a ketamine-alfentanil combination over equianalgesic doses of
      either component. IMPLICATIONS: In a double-blind, controlled trial, we
      administered doses of an opioid analgesic (alfentanil), an N-methyl-D-aspartate
      receptor antagonist (ketamine), or their combination to normal volunteers and
      found no advantage of the combination over a larger dose of either drug alone in
      relieving pain caused by painful chemical stimulation.

PMID- 9620516
TI  - Vasovagal cardiac arrest during the insertion of an epidural catheter and before
      the administration of epidural medication.

PMID- 9620515
TI  - Experimental pain in healthy human subjects: gender differences in nociception
      and in response to ibuprofen.
AB  - We used electrically induced pain in healthy young subjects to study gender
      differences in nociception and the analgesic efficacy of ibuprofen. Cutaneous
      stimulation of the earlobe allowed measurement of pain detection thresholds and
      maximal pain tolerance. Drug and placebo were each administered twice using a
      double-blind, randomized, multiple cross-over design. Male subjects had greater
      stimulus thresholds (lower nociception) compared with female subjects (18 +/- 0.3
      vs 15 +/- 0.3 volts, mean +/- SEM; n = 10 in each group) and a greater pain
      tolerance (24 +/- 0.4 vs 21 +/- 0.4 volts). Response variability was also greater
      in the male subjects, yet only the men exhibited a statistically significant
      analgesic response to ibuprofen (deltavolts; ibuprofen versus placebo: 2.80 +/-
      0.33 vs -0.18 +/- 0.34; P < 0.05, n = 10). None of these results could be
      attributed to pharmacokinetic differences. The finding that ibuprofen was less
      effective in women than in men has potential clinical significance, especially as
      a factor in the response variability to nonsteroidal antiinflammatory drugs.
      IMPLICATIONS: In this study, we examined ibuprofen, a widely used nonsteroidal
      antiinflammatory drug, for its ability to reduce experimental pain. We found that
      it had such properties in healthy young male subjects but not in young female
      subjects. This is a paradox because many of the painful conditions for which
      nonsteroidal antiinflammatory drugs are used (e.g., rheumatoid arthritis) occur
      more often in women.

PMID- 9620517
TI  - Arterial oxygenation and shunt fraction during one-lung ventilation: a comparison
      of isoflurane and sevoflurane.
AB  - The aim of this study was to evaluate the effect of isoflurane and sevoflurane on
      oxygenation and shunt fraction during one-lung ventilation (OLV). Twenty patients
      undergoing lobectomy for lung cancer and scheduled for long-term OLV were
      enrolled in this study. Patients were allocated to treatment with either
      isoflurane or sevoflurane. Arterial oxygenation, shunt fraction, and hemodynamics
      were evaluated at the end of two-lung ventilation; 20 min after the initiation of
      OLV; 20 min after the application of 4-cm positive end-expiratory pressure (PEEP)
      to the dependent lung; 20 min after 8-cm PEEP; and 20 min after the conversion
      from OLV to two-lung ventilation. There was no significant difference between
      isoflurane and sevoflurane with regard to oxygenation, shunt fraction, or
      hemodynamics during OLV. PaO2 values after the application of 4-cm PEEP increased
      from 131.1 +/- 11.8 mm Hg to 190.6 +/- 22.9 mm Hg in the isoflurane group (P <
      0.05) and from 127.2 +/- 14.3 mm Hg to 192.4 +/- 26.9 mm Hg in the sevoflurane
      group (P < 0.05). The selection of either isoflurane or sevoflurane for OLV was
      made without regard to arterial oxygenation and shunt fraction. PEEP application
      to the dependent lung is useful for improving oxygenation during OLV, but 8-cm
      PEEP had no added effect compared with 4-cm PEEP. IMPLICATIONS: We compared the
      effects of isoflurane and sevoflurane on oxygenation, hemodynamics, and shunt
      fraction during one-lung ventilation in 20 patients undergoing scheduled
      lobectomy for lung cancer. There was no significant difference between isoflurane
      and sevoflurane with regard to oxygenation, shunt fraction, and hemodynamics
      during one-lung ventilation. The application of 4-cm positive end-expiratory
      pressure increased the partial pressure of arterial oxygen during one-lung
      ventilation.

PMID- 9620518
TI  - A new and simple maneuver to position the left-sided double-lumen tube without
      the aid of fiberoptic bronchoscopy.
AB  - The double-lumen tube (DLT) is the mainstay of one-lung ventilation (OLV). We
      sought to determine whether this new intubation maneuver using an endobronchial
      cuff pressure could be substituted for verification by fiberoptic bronchoscope
      (FOB) in most conditions requiring left-sided DLT. Seventy-nine patients
      requiring video-assisted thoracoscopic surgery for pneumothorax or mediastinal
      mass, or open thoracotomy for lung or esophageal cancer were enrolled in this
      study. We used 35F (n = 23), 37F (n = 51), or 39F (n = 5) disposable polyvinyl
      chloride DLTs (Broncho-Cath; Mallinckrodt Medical Ltd., Athlone, Ireland),
      depending on the height and gender of the patients. The DLTs were inserted deeply
      until resistance was felt. At that time, the pilot of the endobronchial cuff was
      connected to the Control-Inflator (VBM Medizintechnik GmbH, Sulz am Neckar,
      Germany) via a three-way stopcock. The bronchial balloon was inflated with 1.0
      2.0 mL of air through the stop-cock until approximately 30 cm H2O of cuff
      pressure was obtained. The DLT was slowly withdrawn until the pressure of the
      Control-Inflator decreased to approximately half the peak pressure during the
      initial phase of removal. At that time, the bronchial balloon was deflated, and
      the DLT was advanced approximately 1.0 cm (1.5 cm for the 39F DLT); using FOB,
      its position was checked by an independent observer not involved in positioning
      the DLTs. The ideal position was defined as that in which the carina was located
      at the same level with the middle 5 mm between the proximal margin of the
      endobronchial balloon and the circumferential black mark. In 50 patients the
      position was ideal, and in 27 patients it was not ideal but was within the margin
      of the safety. There were only two failures. We conclude that if a FOB is
      unavailable or inapplicable, this simple and new maneuver may be used as a
      substitute during the positioning of DLTs. IMPLICATIONS: The correct position of
      the double-lumen tube is vital for one-lung ventilation, which has been confirmed
      with a fiberoptic bronchoscope. We devised a simple maneuver to position the
      double-lumen tube correctly without a fiberoptic bronchoscope.

PMID- 9620519
TI  - Esophageal stethoscope placement depth: its effect on heart and lung sound
      monitoring during general anesthesia.
AB  - Although the esophageal stethoscope has been used for many years, the effect of
      the depth of placement on the quality of the sounds obtained has never been
      investigated. The amplitude and frequency characteristics of the first and second
      heart sound and of inspiratory and expiratory breath sounds were determined at
      various stethoscope depths (from the distal tip) in 17 healthy anesthetized
      adults. The amplitude for each type of sound varied markedly with depth. Maximal
      amplitude for S1 was at 34 +/- 3 cm, for S2 at 27 +/- 2 cm, for inspiratory
      breath sound at 28 +/- 2 cm, and for expiratory breath sound at 26 +/- 2 cm.
      There was a positive linear correlation between the depth of maximal amplitude of
      these sounds and patient height. Peak frequency, in general, did not change with
      depth. We conclude that investigators should measure and document depth when
      performing studies involving the esophageal stethoscope. IMPLICATIONS: Analysis
      of sound from the esophageal stethoscope at various depths reveals that placement
      depth greatly affects the sounds. A depth of 28-32 cm is recommended for clinical
      use; S1, S2, and inspiratory and expiratory sounds have a high amplitude in that
      range.

PMID- 9620520
TI  - Bronchial mucus transport velocity in paralyzed anesthetized patients: a
      comparison of the laryngeal mask airway and cuffed tracheal tube.
AB  - We compared bronchial mucus transport velocity (BTV), an index of mucociliary
      clearance, between the laryngeal mask airway (LMA) and the tracheal tube (TT).
      Forty patients were studied during propofol anesthesia and muscle relaxation with
      rocuronium. BTV was measured 10 and 60 min after insertion of the airway device
      by fiberoptic observation of the movement of methylene blue dye injected onto the
      dorsal surface of the left main bronchus. BTV for the LMA was similar at 10 and
      60 min (13.9 +/- 2.0 and 13.6 +/- 2.1 mm/min, respectively). BTV for the TT was
      significantly faster at 10 min that at 60 min (13.0 +/- 1.4 vs 6.9 +/- 1.2
      mm/min, respectively; P < 0.00001). BTV was similar for both devices at 10 min
      (TT 13.0 +/- 1.4 mm/min versus LMA 13.9 +/- 2.0 mm/min), but was significantly
      faster for the LMA than for the TT at 60 min (LMA 13.6 +/- 2.1 mm/min versus TT
      6.9 +/- 1.2 mm/min; P < 0.00001). We conclude that the LMA impedes mucociliary
      clearance less than the TT in anesthetized patients. This may have implications
      for reducing the risk of retention of secretions, atelectasis, and pulmonary
      infection. IMPLICATIONS: This study compares bronchial mucus transport velocity,
      an index of mucociliary clearance, in anesthetized patients between two airway
      devices, the cuffed tracheal tube and the laryngeal mask airway. We have shown
      that the laryngeal mask airway impairs mucociliary clearance less than the
      tracheal tube. This may have implications for reducing the risk of retention of
      secretions, atelectasis, and pulmonary infection.

PMID- 9620521
TI  - The effect of pneumoperitoneum on intraocular pressure in rabbits with alpha
      chymotrypsin-induced glaucoma.
AB  - Increased intraperitoneal pressure is associated with physiological changes
      including alterations of intraocular pressure (IOP). We have previously shown
      that IOP is not adversely affected by increased intraperitoneal pressure up to 15
      mm Hg in women with no preexisting eye disease. The aim of this study was to
      measure IOP changes associated with increased intraperitoneal pressure (up to 15
      mm Hg) of 2 h duration in 12 rabbits with alpha-chymotrypsin-induced glaucoma. A
      reliable model of glaucoma was created by injecting alpha-chymotrypsin into the
      posterior chamber of the right eye in 12 rabbits. Thereafter, 5 of the 12 rabbits
      with glaucomatous eyes were treated with topical timolol. The left eye was used
      as a control. During pentobarbital general anesthesia, increased intraperitoneal
      pressure up to 15 mm Hg was created by intraperitoneal CO2 insufflation. Body
      temperature and expired CO2 were kept constant throughout the study. IOP
      measurements were made using an electronic pneumotonometer. IOP, mean arterial
      pressure, heart rate, and central venous pressure were recorded in head-up and
      head-down positions before, during, and after increased intraperitoneal pressure.
      The IOP of both eyes, in both treated and untreated rabbits, increased
      significantly from baseline only when increased intraperitoneal pressure
      associated with the head-down position resulted in a significant increase in
      central venous pressure. However, the IOP increase remained within the diurnal
      range. The major finding of this study is that, in a reliable model of glaucoma,
      CO2 pneumoperitoneum was associated with an increase in IOP when a head-down
      position was combined with pneumoperitoneum. IMPLICATIONS: In rabbits with alpha
      chymotrypsin-induced glaucoma, increased intraperitoneal pressure (up to 15 mm
      Hg) resulted in a significant intraocular pressure increase when pneumoperitoneum
      was associated with the head-down position. However, the intraocular pressure
      increase remained within the diurnal range.

PMID- 9620522
TI  - The effect of midazolam and propofol on interleukin-8 from human
      polymorphonuclear leukocytes.
AB  - Anesthetics and sedatives contribute to postoperative immunosuppression.
      Interleukin-8 (IL-8) is a chemotactic and activating factor that mediates
      neutrophil adhesion and margination and is essential for host defense. We
      investigated the effect of anesthetics on isolated human polymorphonuclear
      leukocyte production of IL-8. Healthy human polymorphonuclear leukocytes were
      isolated using a single-step density gradient and stimulated with
      lipopolysaccharide in the presence of varying concentrations of propofol or
      midazolam for up to 20 h. IL-8 was measured in both culture supernatants and cell
      lysates using enzyme immunoassay, and IL-8 mRNA in cells was measured using
      Northern blotting and phosphorimaging. Data were analyzed using Kruskal-Wallis
      analysis of variance or the Mann-Whitney U-test as appropriate.
      Lipopolysaccharide increased extracellular accumulation of interleukin-8, which
      was suppressed by both propofol (P = 0.025) and midazolam (P = 0.028). However,
      intracellular IL-8 increased with exposure to lipopolysaccharide (P = 0.028) and
      remained increased with both anesthetics. Northern blot analysis also revealed
      increased IL-8 mRNA levels in the presence of both midazolam and propofol, which
      was confirmed by molecular imaging. These data strongly suggest that the
      anesthetics modulate transport or secretion of IL-8 protein from the cell.
      Suppression of IL-8 by anesthetics and sedatives may predispose postoperative and
      intensive care patients to infection. IMPLICATIONS: Anesthesia causes immune
      suppression and alters neutrophil function. We investigated the effect of
      propofol and midazolam on interleukin-8, a neutrophil chemotactic agent in human
      neutrophils. Both anesthetics decreased extracellular interleukin-8 accumulation,
      but intracellular levels and mRNA remained high. This suggests that propofol and
      midazolam alter interleukin-8 secretion from cells.

PMID- 9620523
TI  - Oleamide potentiates benzodiazepine-sensitive gamma-aminobutyric acid receptor
      activity but does not alter minimum alveolar anesthetic concentration.
AB  - A naturally occurring brain lipid, cis-9,10-octadeceamide--oleamide (OA), is
      found in increased concentrations in the cerebrospinal fluid of sleep-deprived
      cats, which suggests that it may be an endogenous sleep-inducing substance. We
      studied the effects of this fatty-acid derivative on the function of cloned gamma
      aminobutyric acid (GABA(A)) receptors expressed in Xenopus oocytes. Oocytes were
      injected with cRNA synthesized in vitro to express simple GABA(A) receptors
      (alpha1beta1, alpha3beta1, alpha5beta1, and alpha1beta2 subunit combinations) and
      receptors in which the GABA-induced chloride currents were potentiated in the
      presence of benzodiazepines (alpha1beta1gamma2s and alpha1beta2gamma2s subunit
      combinations). OA only produced significant potentiation of the peak Cl- current
      when applied with GABA to benzodiazepine-sensitive GABA(A) receptors. The peak
      currents of the simple GABA(A) receptors in the presence of OA were either
      unaffected or slightly inhibited by OA, but the overall mean currents were not
      significantly altered. Oleic acid was also capable of potentiating benzodiazepine
      sensitive GABA(A) receptor function. The function of other ligand-gated ion
      channels, such as the N-methyl-D-aspartate receptor (NR1 + NR2A or 2C) and the 5
      HT3 receptor expressed in Xenopus oocytes, were unaffected by OA. Sprague-Dawley
      rats receiving intraperitoneal injections of oleamide (10, 20, or 100 mg/kg)
      showed no change in the minimum alveolar anesthetic concentration (MAC) of
      desflurane required to abolish movement in response to noxious (tail clamp)
      stimulation (control MAC 6.48% +/- 1.28% atm; 100 mg/kg OA MAC 7.05% +/- 0.42%
      atm). These results reinforce the view that oleyl compounds may be natural
      modulators of inhibitory ion channel function, but that these effects contribute
      little to the central nervous system depression produced by volatile anesthetics
      as measured by MAC. IMPLICATIONS: The putative sleep-inducing substance,
      oleamide, potentiates benzodiazepine-sensitive gamma-aminobutyric acid receptor
      function but does not alter desflurane minimum alveolar anesthetic concentration
      in rats.

PMID- 9620524
TI  - The effect of rate of administration on brain concentrations of propofol in
      sheep.
AB  - A marked reduction in the dose of propofol required to achieve the onset of
      anesthesia with slower administration rates has previously been reported, but the
      mechanism of this phenomenon is unclear. We used a chronically instrumented sheep
      preparation to examine the effects of different administration rates of propofol
      on its distribution in the brain using mass balance principles to calculate brain
      concentrations. The administration of 100 mg of propofol i.v. at rates of 200,
      50, and 20 mg/min had minimal effect on both the peak brain concentrations of
      propofol and the total amount of drug entering the brain. The more rapid
      administration rates increased the rate of uptake into the brain but resulted in
      large increases in peak arterial blood propofol concentrations. These faster
      administration rates have previously been associated with high arterial propofol
      concentrations and an increased risk of hypotension. Simulation of titration to
      an end point revealed that the dose sparing previously reported at induction with
      slow administration rates relates only to improved titration to effect, and does
      not result in more anesthesia for a given dose. Therefore, we conclude that the
      administration of propofol over 2 min provides a reasonable rate of induction and
      improved titration to effect, yet avoids excessively high arterial
      concentrations. IMPLICATIONS: Alterations in the rate of administration of
      propofol in sheep have been shown to have little effect on the quantity of
      propofol delivered to the brain. At induction of anesthesia, administration rates
      of approximately 50 mg/min seem likely to provide improved titration to effect
      without excessively prolonging induction.

PMID- 9620525
TI  - Rapid development of tolerance to analgesia during remifentanil infusion in
      humans.
AB  - Studies in experimental animals have demonstrated a rapidly developing acute
      tolerance to the analgesic effect of opioids administered by continuous i.v.
      infusion. The aim of the present study was to determine whether acute tolerance
      plays an important role in the analgesic effect of remifentanil provided by i.v.
      infusion to humans. The analgesic effect of remifentanil, infused at a constant
      rate of 0.1 microg x kg(-1) x min(-1) for 4 h, was evaluated by measuring pain
      tolerance with thermal (2 degrees C water) and mechanical (pressure) noxious
      stimulations in 13 paid volunteers. The constant-rate infusion of remifentanil
      resulted in a threefold increase in pain tolerance with both tests. After
      reaching its maximum in 60-90 min, the analgesic effect of remifentanil began to
      decline despite the constant-rate infusion, and after 3 h of infusion, it was
      only one fourth of the peak value. A comparative rate in the development of acute
      tolerance measured in terms of time to 50% recovery during infusion was 129 +/-
      27 min (mean +/- SD) with the cold water test and 138 +/- 39 min with the
      pressure test. We conclude that the development of tolerance should be included
      in the calculations for target-controlled infusions. IMPLICATIONS: Our study
      shows that tolerance to analgesia during remifentanil infusion is profound and
      develops very rapidly. The administration of opioids during anesthesia based on
      target-controlled infusions should include corrections for the development of
      tolerance.

PMID- 9620526
TI  - The combination of epinephrine and isoproterenol as a simulated epidural test
      dose in isoflurane-anesthetized adults.
AB  - During isoflurane anesthesia, an epinephrine-containing test dose produces
      unreliable heart rate (HR) responses with a high incidence of hypertension,
      whereas an isoproterenol-containing test dose results in a high incidence of
      hypotension. We designed this study to determine whether different combination
      doses of epinephrine and isoproterenol produce reliable HR changes without overt
      fluctuations of systolic blood pressure (SBP). Seventy-five healthy patients were
      anesthetized with 1% end-tidal isoflurane after endotracheal intubation and
      randomized to one of five groups (n = 15 each) according to the combination dose
      given i.v.: epinephrine 15 microg, epinephrine 15 microg + isoproterenol 1.5
      microg, epinephrine 7.5 microg + isoproterenol 3 microg, isoproterenol 3 microg,
      and saline. HR and SBP were measured at 20-s intervals for 4 min after injection.
      Based on the conventional HR criterion (positive if > or = 20 bpm increase), the
      epinephrine 15 microg + isoproterenol 1.5 microg, the epinephrine 7.5 microg +
      isoproterenol 3 microg, and the isoproterenol 3 microg groups yielded 100%
      sensitivities, specificities, and positive and negative predictive values,
      whereas all groups yielded 100% efficacy according to the modified HR criterion
      (positive if > or = 10 bpm increase). Four (27%) and three patients (20%) in the
      epinephrine 15 microg and the epinephrine 15 microg + isoproterenol 1.5 microg
      groups, respectively, developed systolic hypertension (SBP > or = 180 mm Hg),
      whereas four (27%) patients in the isoproterenol 3 microg group developed
      systolic hypotension (SBP < or = 80% of the preinjection value). We conclude that
      epinephrine 7.5 microg + isoproterenol 3 microg provides the most reliable HR
      changes with the least SBP fluctuations. IMPLICATIONS: To test whether an
      epidural catheter may be in a blood vessel, various vasoactive drugs are
      administered during general anesthesia. The authors found that the combination of
      epinephrine 7.5 microg and isoproterenol 3 microg produced the most reliable
      heart rate changes with minimal blood pressure fluctuations.

PMID- 9620527
TI  - The effect of hydroxyethyl starch on platelet aggregation in vitro.
AB  - The effect of hydroxyethyl starch (HES) on hemostasis seems to be minimal when it
      is used in recommended amounts. A number of studies have investigated the effect
      of HES on platelet function when administered in vivo, but there has been no
      study investigating the effect on the isolated platelet function when
      administered in vitro. A photometrical method to assess platelet function in
      platelet-rich plasma (approximately 250 x 10(9) platelets/L) was used with
      platelet aggregation induced using either collagen, epinephrine, adenosine
      diphosphate, or ristocetin. We found a dose-dependent decrease of platelet
      aggregation in vitro with either collagen or epinephrine, but not with adenosine
      diphosphate or ristocetin. However, the changes of HES on platelet aggregation
      were detected only in doses larger than those routinely used in the clinical
      setting. Therefore, we conclude that the influence of HES at the recommended
      doses on initial platelet aggregation may not be clinically relevant.
      IMPLICATIONS: The effect of hydroxyethyl starch on platelet function and
      coagulation is discussed. This study showed no influence on platelets in
      clinically relevant doses in an in vitro model.

PMID- 9620528
TI  - The pharmacokinetics of vecuronium in male and female patients.
AB  - To evaluate the effect of gender on the pharmacokinetics of vecuronium, we
      studied 30 patients (15 male and 15 female) undergoing elective plastic surgery
      with anticipated surgical blood loss of <300 mL under general anesthesia. General
      anesthesia was induced with thiopental 4-6 mg/kg and fentanyl 2-4 microg/kg and
      was maintained with 60% nitrous oxide in oxygen and an end-tidal concentration of
      1.5%-2% enflurane. After a 2-min infusion of vecuronium 100 microg/kg, a modified
      fluorometric assay was used to determine the plasma concentrations of vecuronium
      for 5 h. The results showed that, compared with women, the plasma concentrations
      of vecuronium in men were significantly lower during the first 20 min and that
      the disposition kinetics of vecuronium can be best described mathematically by a
      three-compartment open model in the two groups. The volume of the central
      compartment and the volume of distribution at steady state were 39.6 +/- 8.6 and
      164.8 +/- 29.3 mL/kg, respectively, in women. These values increased
      significantly to 54.4 +/- 14.4 and 201.4 +/- 75.8 mL/kg in men (P < 0.05). When
      the data were calculated on the basis of ideal body weight, the volume of
      distribution of vecuronium was also different between men and women (P < 0.05.
      The half-lives of fast distribution and distribution, the elimination half-life,
      mean residual time, area under the plasma-concentration curve, and plasma
      clearance were not different between the two groups. We conclude that the
      pharmacokinetics of vecuronium are significantly different between genders and
      that and men have the greater volume of distribution of vecuronium. IMPLICATIONS:
      The authors found that, compared with women, men had lower plasma concentrations
      of vecuronium after the i.v. administration of vecuronium and a larger volume of
      distribution of vecuronium. The pharmacokinetic differences may be related to the
      differences in the sensitivity to vecuronium between genders.

PMID- 9620529
TI  - Human malignant hyperthermia associated with desflurane anesthesia.

PMID- 9620530
TI  - Eyelid movement during complete neuromuscular block.

PMID- 9620531
TI  - Intravenous oxytocin in patients undergoing elective cesarean section.

PMID- 9620532
TI  - Intravenous regional anesthesia.

PMID- 9620533
TI  - Does the choice of muscle relaxants really affect postoperative recovery time?

PMID- 9620534
TI  - The changing role of monitored anesthesia care in the ambulatory setting.

PMID- 9620535
TI  - Dissociative monitored anesthesia care not cited.

PMID- 9620536
TI  - Retrieval of air from the arrow antecubital catheter.

PMID- 9620537
TI  - Laryngeal mask insertion techniques.

PMID- 9620538
TI  - The differential effects of prostaglandin E1 and nitroglycerin on regional
      cerebral oxygenation.

PMID- 9620539
TI  - Supraventricular tachycardia induced by Datex patient monitoring system.

PMID- 9620540
TI  - Lipid peroxidation of rat myocardial tissue following daunomycin administration.
AB  - Daunomycin-induced cardiotoxicity has been regarded to be the result of oxygen
      mediated lipid peroxidation of cell membranes. The aim of the present work was to
      evaluate the extent of lipid peroxidation in rat heart after administration of
      this anticancer drug and, further, to examine possible activation of some
      endogenous antioxidant defense systems. Myocardial tissue from both control and
      drug-treated rats was tested for lipid peroxidation using a selective third-order
      derivative method that is based on the analysis of the free malondialdehyde
      produced. Determination of reduced/oxidized glutathione levels and measurement of
      the activity of DT-diaphorase, glutathione-S-transferase, glutathione reductase,
      glucose-6-phosphate dehydrogenase and NADPH-cytochrome P-450 reductase were also
      carried out using literature methods. Significant increase of malondialdehyde
      content, and DT-diaphorase and glutathione-S-transferase activities were found in
      myocardial tissue from daunomycin-treated rats. On the other hand, reduced and
      oxidized glutathione levels were significantly decreased while the activity of
      glutathione reductase, glucose-6-phosphate dehydrogenase and NADPH-cytochrome P
      450 reductase remained unchanged after daunomycin administration. The results of
      the present study give further evidence that daunomycin can induce lipid
      peroxidation in heart. However, additional experimentation is needed in order to
      delineate the molecular details of this process as well as of the mechanisms
      evolved to limit it.

PMID- 9620541
TI  - DNA oxidation by potassium bromate; a direct mechanism or linked to lipid
      peroxidation?
AB  - Following incubation of calf thymus DNA with potassium bromate (KBrO3) and
      glutathione (GSH), a statistically significant increase in the concentration of 8
      oxodeoxyguanosine (8-oxodG) relative to deoxyguanosine was measured. This was GSH
      dependent and was associated with loss of GSH during incubation. In contrast, 8
      oxodG was not found to be elevated significantly in either total tissue DNA or
      mitochondrial DNA isolated from Sprague-Dawley rat kidney perfused in situ with
      KBrO3 (5 mM) for 15 min or 1 h. There was also no associated increase in the
      level of renal lipid peroxidation or reduced or oxidised GSH. Following
      intraperitoneal administration of KBrO3 to Sprague-Dawley rats, a dose of 100
      mg/kg (maximum tolerated) gave evidence for oxidative stress in the kidney at 24
      h as indicated by a significant increase in lipid peroxidation (P < 0.05) and
      oxidised GSH (P < 0.05). This was associated with a greater than 2-fold,
      significant (P < 0.01) increase in the level of 8-oxodG in kidney total DNA and a
      57% (not statistically significant) increase in kidney mitochondrial 8-oxodG.
      Pretreatment of rats with diethylmaleate (DEM) to deplete GSH, elevated the
      toxicity of 100 mg/kg KBrO3. However, at a dose of 20 mg/kg, no change in any of
      the parameters indicative of kidney oxidative stress (including indicators of
      oxidative DNA damage; 8-oxodG or etheno-DNA adducts, which can be produced by
      lipid peroxides) was seen either with or without DEM pretreatment with the
      exception of a small but statistically significant (P < 0.05) increase in
      mitochondrial 8-oxodG when KBrO3 was given following DEM pretreatment. DNA
      oxidation in the kidney is therefore not inhibited by GSH depletion (contrasting
      with in vitro findings) and requires a sustained exposure at a near-toxic
      concentration of KBrO3 which is associated with lipid peroxidation and GSH
      oxidation. The results do not support a role, in rat kidney, of a direct, GSH
      mediated mechanism for KBrO3-induced DNA oxidation as seen in vitro.

PMID- 9620542
TI  - Evaluation of the direct genotoxic potential of cadmium in four different rodent
      cell lines.
AB  - Cadmium is a toxic environmental contaminant that is carcinogenic in humans and
      laboratory animals. Although the mechanism underlying cadmium carcinogenesis has
      not yet been determined experimental evidence suggests that the stress-inducible,
      metal-binding proteins, metallothioneins, may mediate organ specificity. In the
      present study, four different rodent cell lines (Chinese hamster ovary cells, rat
      L6 myoblast cells, rat Clone 9 liver cells, and rat TRL 1215 liver cells) were
      exposed to 0, 1, 5, 10, 50, or 100 microM CdCl2 and monitored for evidence of
      direct DNA damage. A microfiltration assay was used to measure DNA strand breaks
      and a filter-binding assay was used to measure DNA-protein crosslinks, two
      lesions that have been associated with cadmium exposure and may mediate
      genotoxicity of the metal. Although variability in sensitivity to DNA damage was
      evident between the different cell lines, in all of the cell lines tested,
      increases in DNA damage were observed only at cadmium doses that completely
      arrested cell growth. In addition, in three of the four cell lines tested,
      induction of metallothionein had no substantial protective effect against cadmium
      induced cytotoxicity or genotoxicty. While protection against cadmium-induced DNA
      strand breakage with metallothionein preinduction was observed in the TRL 1215
      rat liver cells, metallothionein preinduction did not protect against cadmium
      induced DNA-protein crosslinking in that cell line. Taken together, our results
      support the hypothesis that cadmium is not directly genotoxic.

PMID- 9620543
TI  - Kinetics of aluminum disposition after ingestion of low to moderate
      pharmacological doses of aluminum.
AB  - We assessed the kinetics of aluminum uptake and elimination by tissues of Sprague
      Dawley rats following a single gavage dose of 0, 0.25, 0.5, or 1 mmol Al/kg body
      weight (b.w.) in 1 ml of 16% citrate (equivalent to 0-650 mg Al to a 70-kg
      human). Serum, liver, kidney, and tibia aluminum concentrations were measured 15,
      30, 60, 120, 270, and 360 min after dosing. Serum aluminum concentrations were
      proportional to dose in rats dosed with 0.25 or 0.5 mmol Al/kg b.w. but were not
      proportional to dose for rats dosed with 1 mmol Al/kg b.w. Elimination half-lives
      of serum aluminum were similar for all treatments (102-119 min) which suggests
      that the non-linear aluminum kinetics in serum reflected a difference in
      absorption of the highest dose. Although fasted rats dosed with 0.25 or 1 mmol
      Al/kg b.w. with citrate absorbed aluminum with similar efficiency (4.2% of dose),
      the length of the absorptive period was prolonged in the rats given the highest
      does. Total absorbed aluminum mass in rats dosed with 0.25 and 0.5 mmol vs. 1
      mmol Al/kg b.w. reached a plateau at 120 vs. 270 min after dosing, respectively.
      The kinetics of aluminum in liver, bone, and kidney were generally dose
      independent. Elimination half-lives of liver aluminum were similar for all
      aluminum treatments (267-465 min); elimination half-lives could not be estimated
      in bone and kidney because of turnover exceeded the 6 h collection period.

PMID- 9620544
TI  - The enzyme inducers 3-methylcholanthrene and phenobarbital affect the activities
      of glucocorticoid hormone-regulated enzymes in rat liver and kidney.
AB  - 3-Methylcholanthrene, an inducer of P448-type cytochromes (mostly 1A1 and 1A2),
      and phenobarbital, an inducer of P450-type cytochromes (mostly 2B1 and 2B2), are
      prototypical for the actions of many xenobiotics. They cause endocrine disruption
      by affecting, among others, steroid hormone levels. Rats were treated with single
      bolus doses of 3-methylcholanthrene or phenobarbital, and enzyme activities that
      are controlled by glucocorticoids were measured in liver and kidney. The
      activities of the cytosolic enzymes L-alanine aminotransferase, indoleamine 2,3
      dioxygenase (L-tryptophan pyrrolase), phosphoenolpyruvate carboxykinase, L-serine
      dehydratase and L-tyrosine aminotransferase were affected in a similar fashion:
      an initial activity reduction followed by two overshoots of activity 1 and 2 days
      after dosing. 3-Hydroxy-3-methylglutaryl coenzyme A reductase, the microsomal key
      enzyme of sterol synthesis, responded with a temporary reduction of activity only
      and evidently lost its diurnal rhythm. The time course of these changes is most
      likely caused by a combination of sub-physiological levels of glucocorticoids
      plus changes of other regulatory hormones elicited by feed intake, postprandial
      state, etc. A possible role for a combined action of the arylhydrocarbon (Ah) and
      glucocorticoid receptors in the effects of 3-methylcholanthrene is also
      suggested.

PMID- 9620545
TI  - Further evaluation of the incorporation of an immunotoxicological functional
      assay for assessing humoral immunity for hazard identification purposes in rats
      in a standard toxicology study.
AB  - A previous study (Ladics et al., 1995) conducted in our laboratory using the
      known immunosuppressant agent, cyclophosphamide, indicated that a functional
      assay for assessment of humoral immunity may be conducted in rats in a standard
      toxicology study. The objective of this study was to further examine the
      feasibility of conducting an immunotoxicological assay for assessing humoral
      immunity in rats in a standard toxicology study using a chemical, carbon
      tetrachloride (CCl4), whose principal target organ of toxicity is not the immune
      system. Specifically, the previous study and this study were done to determine
      whether the conduct of an assay for assessing humoral immune function would
      affect standard toxicological endpoints. Male CD rats were untreated or dosed
      orally for 30 or 90 days, excluding weekends, with vehicle or 12.5 or 25 mg/kg
      CCl4. Six days prior to sacrifice, selected rats were injected intravenously with
      sheep red blood cells (SRBC) for assessment of humoral immune function. One day
      prior to necropsy, blood for hematological and clinical chemical measurements was
      collected from each rat. On the day of necropsy standard protocol tissues were
      collected, weighed, processed to slides, and later examined microscopically. One
      half of each spleen was used to assess spleen cell numbers and quantitate
      lymphocyte subsets (Thelper; Tcyt/sup; total T- and B-cells) by flow cytometry.
      Serum was analyzed for anti-SRBC IgM antibody by using an enzyme-linked
      immunosorbent assay. Administration of 12.5 and 25 mg/kg CCl4 for 30 days
      decreased SRBC-specific serum IgM levels 42 and 45%, respectively, while 25 mg/kg
      CCl4 for 90 days increased SRBC-specific IgM levels by 50%. CCl4 did not alter
      splenic lymphocyte subset numbers nor the weight nor morphology of lymphoid
      organs. Exposure to 25 mg/kg CCl4 did increase liver weight and serum sorbitol
      dehydrogenase levels, as well as produce centrilobular fatty change. SRBC
      administration did not alter any hematological or clinical chemistry parameters,
      nor lymphocyte subset numbers. With the expected exception of the spleen (slight
      increase in number and size of germinal centers), administration of SRBC did not
      significantly alter the weights or morphology of routine protocol tissues.
      Furthermore, administration of SRBC did not mask the rather mild hepatotoxic
      effects of CCL4 exposure observed in this study. Based on these and previous
      findings, it appears that a functional assay for assessing humoral immunity may
      be conducted in animals on standard toxicology study without altering standard
      toxicological endpoints.

PMID- 9620547
TI  - Inhibition of mSOS-activity by binding of phosphatidylinositol 4,5-P2 to the mSOS
      pleckstrin homology domain.
AB  - There are several recently reported examples of inositol phospholipids binding to
      pleckstrin homology (PH) domains of proteins. The PH domain of SOS, a guanine
      nucleotide exchange factor for Ras, binds to phosphatidylinositol 4,5
      bisphosphate (PtdIns4,5P2). We found that binding of PtdIns4,5P2 to 6-his-tagged
      recombinant mSOS in vitro inhibits the ability of SOS to catalyze the association
      of GTP on p21RAS. This inhibition was specific for PtdIns4,5P2: a number of other
      phosphatidylinositols and phosphatidylserine failed to inhibit Ras GTP
      association. We confirmed that the specificity of binding of PtdIns's to
      recombinant GST-SOS-PH domain is the same as the specificity of PtdIns's for
      inhibition of SOS activity: namely, that only PtdIns4,5P2 binds significantly to
      the SOS-PH domain. In addition, the inhibition of Ras GTP-binding is not blocked
      by excess free inositols suggesting that SOS binds to PtdIns4,5P2 with higher
      affinity than it binds to free inositols. Addition of SOS-PH domain protein
      prevented the inhibition of SOS by PtdIns4,5P2 as did addition of the high
      affinity PtdIns4,5P2-binding drug neomycin. This confirmed that SOS inhibition is
      mediated by the SOS-PH domain binding to the inositol moiety of PtdIns4,5P2.
      Binding of Grb2 to SOS did not prevent the inhibition of SOS by PtdIns4,5P2
      suggesting that there must be another mechanism for regulating this inhibition.
      These findings show that the phospholipid PtdIns4,5P2 can suppress the activity
      of an enzyme involved in signal transduction and suggest that this inhibitory
      effect must be relieved when SOS is activated.

PMID- 9620546
TI  - Full activation of MEN2B mutant RET by an additional MEN2A mutation or by ligand
      GDNF stimulation.
AB  - Germline mutations of RET gene, encoding a receptor tyrosine kinase, have been
      associated with the MEN2A and MEN2B inherited cancer syndromes. In MEN2A
      mutations affecting cysteine residues in the extracellular domain of the receptor
      cause constitutive activation of the tyrosine kinase by the formation of
      disulfide-bonded homodimers. In MEN2B a single mutation in the tyrosine kinase
      domain (Met918Thr) has been identified. This mutation does not lead to dimer
      formation, but has been shown (both biologically and biochemically) to cause
      ligand-independent activation of the Ret protein, but to a lesser extent than
      MEN2A mutations. Intramolecular activation by cis-autophosphorylation of RetMEN2B
      monomers has been proposed as a model for activation, although alternative
      mechanisms can be envisaged. Here we show that the activity of RetMEN2B can be
      increased by stable dimerization of the receptor. Dimerization was achieved
      experimentally by constructing a double mutant receptor with a MEN2A mutation
      (Cys634Arg) in addition to the MEN2B mutation, and by chronic exposure of
      RetMEN2B-expressing cells to the Ret ligand GDNF. In both cases full activation
      of RetMEN2B, measured by 'in vitro' transfection assays and biochemical
      parameters, was seen. These results indicate that the MEN2B phenotype could be
      influenced by the tissue distribution or concentration of Ret ligand(s).

PMID- 9620548
TI  - FRA7G extends over a broad region: coincidence of human endogenous retroviral
      sequences (HERV-H) and small polydispersed circular DNAs (spcDNA) and fragile
      sites.
AB  - FRA7G is an aphidicolin-inducible common fragile site at human chromosomal band
      7q31.2. This region is frequently altered in a number of different tumor types
      including prostate, breast, and ovarian cancer. It has also been hypothesized
      that this region contains an important tumor suppressor gene which is mutated
      during the development of these cancers or an oncogene which is amplified. We
      previously used a FISH-based approach to isolate YAC clones which spanned FRA7G.
      In this report, we describe the isolation and restriction endonuclease mapping of
      three overlapping P1 clones which cover FRA7G and the region frequently altered
      in the different cancers. FISH-based analysis of these clones reveals that
      aphidicolin-induced breakage in the FRA7G region occurs over a region of at least
      300 Kb in length. We have also localized a previously sequenced BAC clone to this
      region. The sequence obtained from this clone reveals the presence of an
      endogenous retroviral sequence (HERV-H) in the midst of the FRA7G region as well
      as sequences with homology to small polydispersed circular DNAs (spcDNAs). Thus
      for the first two cloned common fragile sites, FRA7G and FRA3B, there is an
      association with both spcDNAs and hot-spots for viral integration.

PMID- 9620549
TI  - v-fps causes transformation by inducing tyrosine phosphorylation and activation
      of the PDGFbeta receptor.
AB  - The v-fps oncogene encodes an activated tyrosine kinase which is capable of
      transforming fibroblasts. In this report, we provide evidence that within a few
      minutes of activation of the tyrosine kinase activity of v-Fps, tyrosine
      phosphorylation of the platelet derived growth factor (PDGF) beta receptor is
      observed. Further, sustained expression of activated v-Fps results in a down
      regulation of the PDGF receptor both at the level of the mRNA (approximately 4-8
      fold), but even more markedly at the level of the receptor protein (> 100-fold).
      The kinase activity of the v-Fps oncoprotein was found to be required for both
      the induction of PDGF receptor tyrosine phosphorylation and ultimately the
      reduced receptor protein levels. Tyrosine phosphorylation of a kinase inactive
      PDGF receptor was also demonstrated in cells which also express v-fps, but this
      was not sufficient to induce transformation. Only cells expressing both v-fps and
      a wild type PDGF receptor were able to form colonies in soft agar. These findings
      suggest that wild type v-fps may use tyrosine phosphorylation of the PDGFbeta
      receptor to constitutively activate the kinase activity of the receptor,
      resulting in a sustained proliferative signal and fibroblast transformation.

PMID- 9620550
TI  - Lymphadenopathy, splenomegaly, and altered immunoglobulin production in BCL3
      transgenic mice.
AB  - The candidate proto-oncogene BCL3 was isolated through its involvement in the
      t(14;19) found in chronic lymphocytic leukemia and other B-cell neoplasms. As a
      member of the I kappaB family, BCL3 plays a role in the immune response by
      interactions with the NF-kappaB family of transcription factors. In order to
      study the role of BCL3 overexpression in lymphoid malignancies, we generated five
      lines of E mu-BCL3 transgenic mice. Transgenic animals develop normally but show
      splenomegaly and an accumulation of mature B cells in lymph nodes, bone marrow
      and peritoneal cavity. A hyperresponsive immune system is suggested by the
      follicular hyperplasia and plasmacytosis in lymph nodes of unimmunized animals,
      increased incidence of antibodies to self-antigens, and a heightened response to
      cross-linking of surface IgM. Statistically significant decreases in serum IgM
      and IgG3, but an increase in IgG1 and IgA were also observed. No lymphoid
      neoplasms have been identified in transgenic animals. The expansion of B cells in
      vivo is consistent with the overexpression of BCL3 as being one step in the multi
      step process of leukemogenesis. The phenotype also suggests that BCL3 plays a
      part in B cell proliferation and isotype switching.

PMID- 9620551
TI  - Human male germ cell tumor resistance to cisplatin is linked to TP53 gene
      mutation.
AB  - Male germ cell tumors (GCTs) are uniquely sensitive to cisplatin-based
      chemotherapy, with more than 90% of newly diagnosed cases cured. The underlying
      cause for resistance to treatment in 20-30% of metastatic lesions remains to be
      identified. Unlike other solid tumors, no mutations in the TP53 gene have been
      identified to date in random panels of GCT specimens, which could account for the
      exquisite sensitivity of these tumors to genotoxic insult. However, in a panel of
      resistant GCTs that did either not respond to cisplatin-based chemotherapy or
      subsequently relapsed and resulted in the death of the patient, we have now
      identified a subset of tumors to contain TP53 mutations within exons 6-9. A cell
      line derived from one of these tumors (228A) displayed the same TP53 mutation as
      the tumor specimen, expressed only mutant TP53 mRNA, and exhibited a relative
      resistance to cisplatin in vitro in comparison to a cell line (218A) derived from
      a responsive tumor with wild-type TP53. The resistant cell line displayed a much
      reduced apoptotic cell death and did not exhibit an induction of transcription of
      the p53-responsive genes WAF1 and MDM2 following cisplatin treatment, compared to
      that observed in the sensitive cell line. The levels of bax, an agonist of
      apoptosis, were found to be reduced in the resistant cell line. The simplest
      explanation for the resistance of this subset of GCTs that are resistant to
      cisplatin-based chemotherapy, is the inability of the cells to mount an apoptotic
      response following exposure due to a functionally inactivating mutation in the
      TP53 gene.

PMID- 9620552
TI  - Retinal dysplasia in mice lacking p56lck.
AB  - The product of the proto-oncogene p56lck is a non-receptor tyrosine kinase member
      of the Src family. It is found in T cells (Marth et al., 1985, 1988) and in the
      mouse brain (Omri et al., 1996; Van Tan et al., 1996). In this report, we
      describe experiments showing that Lck is present in the mouse retina neurons. Lck
      gene expression was identified after isolating and sequencing the specific 5' and
      3' part of the cDNA obtained by RT-PCR. In adult retina Lck immunoreactivity was
      most abundant in photoreceptor cells and within the outer plexiform layers.
      Staining was also observed in the inner nuclear and plexiform layers. In
      transgenic mice, the disruption of the Lck gene had serious consequences on the
      organization of the retina causing retinal dysplasia. These mice have partial
      retinal detachment with infolding and rosette formation in the photoreceptor
      sheet. These retinal abnormalities observed in Lck deficient mice lead to the
      loss of normal architecture of the photoreceptor and the inner nuclear layers,
      and provide an important role of Lck protein in the retina development. The lack
      of the Lck protein produces a spectrum of retinal pathology that resembles human
      retinopathy of prematurity (ROP).

PMID- 9620553
TI  - Release of the mitogen lysophosphatidylinositol from H-Ras-transformed
      fibroblasts; a possible mechanism of autocrine control of cell proliferation.
AB  - Lysophosphatidylinositol (LysoPtdIns) is formed by a constitutively-active
      phosphoinositide-specific phospholipase A2 in Ras-transformed cells and can
      stimulate cell proliferation. To evaluate whether LysoPtdIns could function as an
      autocrine modulator of cell growth, we examined whether LysoPtdIns can be
      released in the medium of Ras-transformed FRT-Fibro fibroblasts and thyroid
      cells. Here, we report that LysoPtdIns accumulates in the extracellular space of
      these lines and reaches levels up to tenfold higher than in the case of normal
      cells. Moreover, the ionophore A23187 increased the levels of the lysolipid in
      the extracellular medium. Extracellular LysoPtdIns was rapidly hydrolyzed to
      inositol 1:2-cyclic phosphate. LysoPtdIns induced thymidine incorporation in FRT
      Fibro Ha-Ras fibroblasts, whereas inositol cyclic 1:2-cyclic phosphate did not
      affect cell growth per se, nor did it interfere with the LysoPtdIns mitogenic
      activity. We hypothesize that in Ras-transformed fibroblasts the formation and
      release of LysoPtdIns may function as an autocrine mechanism that participates in
      the Ras-dependent stimulation of cell growth.

PMID- 9620554
TI  - The human hepatitis B virus transactivator X gene product regulates Sp1 mediated
      transcription of an insulin-like growth factor II promoter 4.
AB  - Human hepatitis B virus (HBV) is one of the causative agents of hepatocellular
      carcinoma (HCC). The virus encodes a 17 kDa protein, X, which is known to be a
      causative agent in the formation of HCC. An insulin-like growth factor-II (IGF
      II) is expressed during the formation of HCC. Among the four promoters of the IGF
      II gene, promoters 2, 3 and 4 become activated during the formation of HCC. The
      high frequency of detection of hepatitis B virus X (HBV-X) antigen in liver cells
      from patients with chronic hepatitis, cirrhosis, and liver cancer suggested that
      the expressions of HBV-X and IGF-II are associated. Studies were carried out to
      test the relationship between the HBV-X gene product and the activation of IGF-II
      promoter 4. We demonstrated that the HBV-X protein increases the endogenous IGF
      II expression from promoter 3 and 4 of IGF-II gene. Analysis of the fourth
      promoter of IGF-II gene showed that the HBV-X gene product positively regulates
      transcription. Two copies of a motif are responsible for conferring HBV-X
      regulation on the fourth promoter of IGF-II. These motifs have been identified as
      Sp1 binding sites. Sp1 binding to IGF-II P4 promoter was identified by gel
      mobility shift assay using purified Sp1. By using a GAL4-Sp1 fusion protein it
      was demonstrated that HBV-X positively regulates the Spl mediated transcriptional
      activity of IGF-II in vivo. A protein-affinity chromatography experiment showed
      that HBV-X protein does not bind directly to Sp1, but HBV-X does augment the DNA
      binding activity of the phosphorylated form of Sp1 in HepG2 cells. Sp1 was
      phosphorylated by HBV-X and its DNA-binding activity was up-regulated upon HBV-X
      transfections. Various HBV-X mutant expression vectors were used for the
      demonstration of specific interactions between Sp1 and HBV-X. These results
      indicate that HBV-X functions as a positive regulator of transcription, and that
      Sp1 is a direct target for the transcriptional regulation of IGF-II. Increasing
      the DNA binding ability of the phosphorylated form of Sp1 by HBV-X might be an
      important mechanism for regulating the IGF-II gene expression and possibly
      promoting cell division during hepatic carcinogenesis. Our experimental results
      suggest that expression of HBV-X might induce the expression of IGF-II and the
      IGF-II might play a role in hepatitis B virus pathogenesis during the formation
      of HCC.

PMID- 9620555
TI  - DOC-2, a candidate tumor suppressor gene in human epithelial ovarian cancer.
AB  - Using RNA fingerprinting (RAP) strategy and Northern blot analysis, we identified
      a differentially expressed sequence DOC-2 which is detectable in all normal human
      ovarian surface epithelial (HOSE) cell cultures but not in ovarian cancer cell
      lines and tissues. Subsequent cloning of DOC-2 from a cDNA library generated from
      the HOSE cells was carried out using the 3' and 5' RACE approach. A 3268 base
      pair full length cDNA of DOC-2 was isolated and sequenced. The predicted protein
      has a length of 770 amino acids. Homology search of all NCBI sequences indicated
      that the amino acid sequence of DOC-2 shares 93% homology with the mouse
      p96/mDab2 phosphoprotein and has a phosphotyrosine interacting domain (PID) and
      multiple SH3 binding motifs. Chromosomal localization by FISH showed that the DOC
      2 gene is located on 5p13. Western blot analysis showed that the 105 kDa DOC-2
      protein was down-regulated in all the carcinoma cell lines. In-situ
      immunohistochemistry performed on normal ovaries, and benign, borderline and
      invasive ovarian tumor tissues showed down regulation of DOC-2 protein
      particularly in serous ovarian tumor tissues. When DOC-2 was transfected into the
      ovarian carcinoma cell line SKOV3, the stable transfectants showed significantly
      reduced growth rate and ability to form tumors in nude mice. These data suggest
      that down-regulation of DOC-2 may play an important role in ovarian
      carcinogenesis.

PMID- 9620556
TI  - Microsatellite mutation rates in cancer cell lines deficient or proficient in
      mismatch repair.
AB  - A selectable system has been used to determine mutation rates within a
      microsatellite sequence in human cancer cell lines with or without defects in
      mismatch repair. A sequence consisting of 17 repeats of poly (dC-dA).poly(dT-dG)
      [abbreviated as (Ca)17] was inserted near the 5' end of the bacterial neomycin
      resistance gene in a plasmid vector, such that the reading frame of the neo gene
      is disrupted. This plasmid was introduced into cancer cell lines, where it became
      integrated into the cellular genome. Clones with insertions or deletions of CA
      repeats that restored the normal reading frame of the neo gene were selected in
      G418, and mutation rates were determined by fluctuation analysis. The rates of
      reversion in LoVo cells, which are deficient for hMSH2, were about one in a
      thousand per generation, which is approximately two orders of magnitude higher
      than in the repair-proficient HT-1080 human fibrosarcoma cell line. The mutation
      rates in H6 cells, which are derived from the hMLH1-deficient HCT116 line, were
      more heterogeneous than in LoVo, but all were considerably higher than in the
      repair-proficient line. Nearly all of the revertants of the repair-deficient
      lines had deletions of a single CA-repeat from the microsatellite sequence,
      whereas repair-proficient cells had a broader spectrum of mutations.

PMID- 9620557
TI  - The H19 TATA-less promoter is efficiently repressed by wild-type tumor suppressor
      gene product p53.
AB  - The developmentally regulated H19 gene displays several remarkable properties:
      expression of an apparently non-translated mRNA, genomic imprinting (maternal
      allele only expressed), relaxation of the imprinting and/or epigenetic lesions
      demonstrated in some tumors. Despite several observations after relaxation of
      imprinting status of the gene, data on trans and cis-acting factors required for
      the human H19 gene expression are still missing. As a first approach to address
      identification of factors involved in the regulation of the gene, we found that
      cells from a p53 antisense-transfected HeLa clone displayed increased amounts of
      H19 transcripts when compared to the non-transfected cells. Moreover, a HeLa
      clone stably transfected with a temperature sensitive (ts) 143 Ala p53 mutant
      exhibited temperature-dependent regulation of H19 expression. This preliminary
      indication of the repressing effect of the p53 protein on H19 expression has been
      confirmed by transient cotransfection experiments in HeLa cells, using luciferase
      surrogate constructs under the control of the 823 bp sequence immediately
      upstream of the transcription start point of the H19 gene, and different
      constructs containing sense, antisense or a ts 143 Ala mutant p53 cDNA. We
      observed an increase of H19 promoter-driven activity in transient cotransfections
      with the antisense p53 cDNA and the temperature sensitive mutant p53 at the non
      permissive temperature, but a decrease with sense wild-type p53 cDNA.
      Furthermore, the cotransfection experiments were repeated in a cell line lacking
      endogenous p53. (Calu 6 cells) and the results provided additional evidence for a
      down regulation of the expression of the H19 gene by the p53 protein.

PMID- 9620558
TI  - A highly conserved processed PTEN pseudogene is located on chromosome band 9p21.
AB  - PTEN/MMAC1/TEP1, encoding a dual-specificity phosphatase, is a tumor suppressor
      gene which has recently been cloned and mapped to chromosome 10q23.3. We have
      shown that germline mutations of PTEN are present in individuals with two
      hamartoma syndromes: Cowden Syndrome, associated with a predisposition to breast
      and thyroid cancers, and Bannayan-Zonana syndrome. Somatic mutations of PTEN have
      been reported in a variety of human cancer cell lines, suggesting a potential
      role for this gene in the pathogenesis of human malignancies. We report the
      identification of a highly conserved PTEN processed pseudogene, psiPTEN, which
      shares over 98% homology with the coding region of functional PTEN, and its
      localisation to chromosome 9p21. The high sequence homology of psiPTEN with the
      PTEN transcript may potentially lead to misinterpretation when performing
      mutation analyses based on cDNA templates. Caution should be exerted when using
      such screening approaches.

PMID- 9620560
TI  - Oligomerization of p53 is necessary to inhibit its transcriptional
      transactivation property at high protein concentration.
AB  - We have previously shown that transactivation by tumor suppressor protein p53 can
      be inhibited in vivo at elevated protein concentrations. In this study we
      characterize the structural requirements of this function. We show that
      oligomerization domain of p53 is involved in loss of transactivation at high
      protein concentrations: mutants not able to oligomerize are neither able to
      suppress transactivation, although these transactivating properties can be
      untouched.

PMID- 9620559
TI  - Akt2 mRNA is highly expressed in embryonic brown fat and the AKT2 kinase is
      activated by insulin.
AB  - Akt2 encodes a protein-serine/threonine kinase containing a pleckstrin homology
      domain characteristic of many signaling molecules. Although there has been
      extensive interest in the mechanism by which the closely-related Akt kinase
      participates in phosphatidylinositol 3-kinase-mediated signaling, comparatively
      little is known regarding the expression and function of Akt2. This manuscript is
      the first to describe Akt2 mRNA expression in the developing mouse and the
      activation of AKT2 by insulin. These studies demonstrate that Akt2 is especially
      abundant in brown fat and, to a lesser extent, skeletal muscle and liver, tissues
      which are highly insulin-responsive and play a role in glucose metabolism.
      Endogenous Akt2 expression also is upregulated in fully-differentiated C2C12
      myotubes and 3T3-L1 adipocytes, suggesting that these murine cell lines represent
      useful in vitro models for studies of Akt2 function. We show that HA-tagged AKT2
      is activated in response to insulin stimulation in vitro and that activation of
      AKT2 is not induced in cells pretreated with wortmannin, an inhibitor of
      phosphatidylinositol 3-kinase. These data suggest that Akt2 expression is
      fundamental to the differentiated state of fat and muscle cells and that
      activation of AKT2 kinase by insulin is mediated through the phosphatidylinositol
      3-kinase signaling pathway.

PMID- 9620561
TI  - Host TIMP-1 overexpression confers resistance to experimental brain metastasis of
      a fibrosarcoma cell line.
AB  - Within the tumor-stromal microenvironment a disrupted balance between matrix
      metalloproteinases (MMPs) and their inhibitors compromises the integrity of the
      extracellular matrix and promotes malignancy. Tissue inhibitors of
      metalloproteinases (TIMPs) have been linked to tumor suppression in studies of
      genetically altered tissue culture cells and in analyses of clinical specimens in
      situ. We generated transgenic mice as a model system to test the relationship
      between TIMP-1 levels in a host organ and susceptibility to experimentally
      targeted metastasis. Ectopically overexpressed TIMP-1 in the brain resulted in a
      tissue microenvironment with elevated protein levels of this natural MMP
      inhibitor. Metastatic challenge provided by lacZ-tagged fibrosarcoma cells
      permitted high-resolution analysis of metastatic load and pattern. We found that
      elevated host TIMP-1 imposed resistance to experimental metastasis of
      fibrosarcoma: In TIMP-1 overexpressing mice, brain metastases were significantly
      reduced by 75% compared to wild-type littermates. Our findings demonstrate that
      ectopic TIMP-1 expression efficiently exerts a suppressive effect on
      metastasizing tumor cells.

PMID- 9620562
TI  - Fumes from the spleen.

PMID- 9620563
TI  - The relationship between congenital cardiovascular malformations and spontaneous
      abortion in preceding pregnancy.
AB  - Previous studies have shown an increased frequency of spontaneous abortions in
      the pregnancy preceding a fetus or a newborn with neural tube defect (NTD)
      compared with a normal newborn. One explanation of this observation is the
      trophoblastic cell rest hypothesis put forward by Knox and Clarke, suggesting a
      teratogenic interaction between the developing embryo and pathological remnants
      of a previous pregnancy. The other explanation is that the previously lost fetus
      was also affected with neural tube defect. The aim of this study was to verify
      whether this observation is also valid for congenital cardiovascular
      malformations (CCVM). Demographic and obstetric data of 99 mothers (58 Jewish and
      41 Bedouin) of newborns who died in the neonatal period from isolated CCVM were
      compared with those of 103 mothers (48 Jewish and 55 Bedouin) of newborns who
      died of congenital defects other than NTD and CCVM. Spontaneous abortions in the
      preceding pregnancy were found in 32% of the cases with CCVM compared with 14% of
      cases with other defects (ODs) (P=0.0012; odds ratio=3.1, 95% confidence interval
      1.5-6.4). This significant difference was independent of maternal age and number
      of pregnancies or deliveries. No difference was found between Jews and Bedouins.
      As there is no indication in the literature that fetuses with isolated CCVM tend
      to be spontaneously aborted, our findings are more supportive of the
      trophoblastic cell rest theory.

PMID- 9620564
TI  - A population-based study of abdominal wall defects in South Australia and Western
      Australia.
AB  - The purpose of this study was to determine the prevalence, clinical
      characteristics, prenatal diagnosis and occurrence of other birth defects with
      abdominal wall defects in births and terminations of pregnancy in South Australia
      (SA) and Western Australia (WA) over the period 1980-90. Cases of gastroschisis,
      exomphalos, bladder exstrophy, cloacal exstrophy and body stalk anomaly were
      ascertained from the WA Birth Defects Registry (1980-90) and the SA Birth Defects
      Register (1986-90). The registers are comparable population-based data
      collections with information on livebirths and stillbirths of at least 400 g
      birthweight or 20 weeks' gestation, and terminations of pregnancy for fetal
      abnormality. The prevalence of gastroschisis was 1.65/10,000 births (59 cases)
      and of exomphalos 2.90/10,000 births (104 cases). There was no significant
      difference in prevalence of exomphalos or gastroschisis between SA and WA for the
      years 1986-90. However, if data from WA for the years 1980-85 were included, SA
      had a significantly higher prevalence of exomphalos (prevalence ratio 1.71,
      confidence interval [CI] 1.16-2.55), although not of gastroschisis (prevalence
      ratio 1.35, CI 0.79-2.32). Exomphalos was significantly more common in mothers <
      20 years (odds ratio [OR] 2.45, CI 1.22-4.86) and in mothers of 40 years or older
      (OR 5.65, CI 1.69-16.77). Gastroschisis was more common in younger mothers (OR
      8.76, CI 4.02-19.32). Both exomphalos and gastroschisis were associated with low
      birthweight, prematurity, intrauterine growth retardation and caesarean section.
      The reason for the higher prevalence of exomphalos in SA than WA was not clear,
      but may be related to differences in prenatal diagnosis. The association between
      maternal age < 20 years and exomphalos raises the possibility of common factors
      in the aetiology of gastroschisis and exomphalos.

PMID- 9620565
TI  - Ethnic-specific predictors of prenatal care utilisation in Hawaii.
AB  - The state of Hawaii has had near-universal health insurance coverage for the last
      20 years. Its highly diverse population offers the opportunity for a unique,
      natural experiment in the United States on the examination of social differences
      in health care utilisation when financial barriers are removed. Therefore, the
      objective of this study is to examine predictors of prenatal care utilisation
      patterns in the four major ethnic groups in Hawaii. The data used in this study
      are the 1979-92 Hawaii livebirth vital record files. A total of 165,301 singleton
      livebirths to Hawaii-resident mothers of Caucasian, native Hawaiian, Japanese or
      Filipino ancestry were selected. Despite near-universal health care coverage in
      Hawaii, a surprising number of women did not adequately utilise prenatal care,
      with large differences between groups. Multivariate analyses indicated that
      similar maternal socio-demographic factors were associated with prenatal care use
      in each ethnic group. Social variation continues to exist among all ethnic groups
      even in the presence of universal access to care. These data emphasise the need
      to address the distinct cultural needs of populations for providing health
      services, and further challenge the assumption that removal of financial barriers
      will ensure a high level of prenatal care use.

PMID- 9620566
TI  - How accurate are antenatal weight measurements? A survey of hospital and
      community clinics in a South Thames Region NHS Trust.
AB  - The accuracy of antenatal weight data recorded in obstetric notes was
      investigated in the 45 hospital and community antenatal clinics within a South
      Thames Region NHS Trust. In order to assess the reliability and validity of all
      60 clinic scales triplicate measurements of body weight for low- and high-weight
      subjects were recorded on each clinical scale and on a calibrated standard scale.
      The quality of weighing practice during antenatal care was investigated by means
      of semi-structured interviews conducted with all 33 midwives who currently
      provide antenatal care within the Trust. Beam balances had the highest
      reliability and validity, whereas scales with spring mechanisms were the least
      accurate. Only 40% of the clinics surveyed had access to beam balances, yet most
      of the maternal weight measurements recorded during antenatal care are likely to
      be out by no more than 1-1.5% of body weight. Weighing practice was generally
      inconsistent, and serial measurements of maternal body weight collected during
      pregnancy are probably too imprecise to provide a sensitive screen for conditions
      associated with unusual weight gain and too inaccurate to assess compliance with
      guidelines for weight gain.

PMID- 9620567
TI  - Carob bean juice: a powerful adjunct to oral rehydration solution treatment in
      diarrhoea.
AB  - In children, the treatment of acute diarrhoea with the World Health Organization
      (WHO) standard oral rehydration solution (ORS) provides effective rehydration but
      does not reduce the severity of diarrhoea. In community practice, carob bean has
      been used to treat diarrhoeal diseases in Anatolia since ancient times. In order
      to test clinical antidiarrhoeal effects of carob bean juice (CBJ), 80 children,
      aged 4-48 months, who were admitted to SSK Tepecik Teaching Hospital with acute
      diarrhoea and mild or moderate dehydration, were randomly assigned to receive
      treatment with either standard WHO ORS alone or a combination of standard WHO ORS
      and CBJ. Three patients were excluded from the study because of excessive
      vomiting. In the children receiving ORS + CBJ the duration of diarrhoea was
      shortened by 45%, stool output was reduced by 44% and ORS requirement was
      decreased by 38% compared with children receiving ORS alone. Weight gain was
      similar in the two groups at 24 h after the initiation of the study.
      Hypernatraemia was detected in three patients in the ORS group but in none of
      those in the ORS + CBJ group. The use of CBJ in combination with ORS did not lead
      to any clinical metabolic problem. We therefore conclude that CBJ may have a role
      in the treatment of children's diarrhoea after it has been technologically
      processed, and that further studies would be justified.

PMID- 9620569
TI  - A comparison of two methods of follow-up in a trial of prophylactic volume
      expansion in preterm babies.
AB  - The outcome at age 2 years of preterm babies recruited into a three-arm
      randomised controlled trial of prophylactic volume expansion was ascertained in
      two ways: from a neurodevelopmental assessment performed by a paediatrician and
      from responses on a brief questionnaire completed by the child's personal health
      visitor. Of 776 babies recruited into the trial, 604 survived to the age of 2
      years and the findings of a paediatric assessment were available for all
      survivors. Questionnaires were sent to the health visitors of 601 of the
      survivors; 513 (85.4%) were returned. There was sufficient information on the
      returned questionnaires to categorise 449 of the children as normal, impaired,
      moderately disabled or severely disabled. We were unable to detect a response
      bias by severity of disability. Agreement on individual questions ranged between
      86.3% and 98.4%. There was some mismatch in the reporting of vision (weighted
      kappa = 0.71) and hearing (weighted kappa = 0.73), with differences in perception
      of level of severity of sensory loss. Health visitors tended to underestimate the
      child's functional level compared with the paediatrician. However, of 56 children
      classified as severely disabled by the paediatrician, 48 were classified
      similarly and eight as moderately disabled on the basis of the questionnaire. The
      end point of the trial was death or severe disability at 2 years of age. There
      was close similarity in the trial results whether based on the paediatric
      assessment or on the questionnaire. Further refinement of the questionnaire is
      needed, but this methodology may be useful in ascertaining the frequency of
      severe disability in large cohorts of babies.

PMID- 9620568
TI  - Traditional nutritional and surgical practices and their effects on the growth of
      infants in south-west Ethiopia.
AB  - A 1-year birth cohort of 1563 infants was seen bi-monthly for the first year of
      life. They comprised all identified infants born in Jimma town, south-west
      Ethiopia, in the year starting 1 Meskren 1985 in the Ethiopian calendar (11
      September 1992). Growth in infancy is poor in this town, as it is in Ethiopia
      more generally: mean z-scores for both weight and length were more than 1.5 SD
      below the median of the NCHS/WHO reference population by 1 year of age, and
      infant mortality was 115/1000. In this paper we examine the weight gain of
      singletons in relation to background variables and to traditional nutritional and
      surgical practices in the families. Confirming work in other areas, sanitation,
      water supply, the income of the family and the mother's literacy were important
      determinants of weight gain. Almost all the infants were initially breast fed,
      and about 80% were still breast fed at 1 year. Many were also given cows' milk
      from 4 months onwards. Breast feeding had beneficial effects up to 8 months of
      age, and cows' milk had beneficial effects after 6 months of age. Supplementary
      feeds of solids and semi-solids were given at appropriate ages, but had no
      detectable benefit. Water was given inappropriately early, but did no detectable
      harm. Episodes of diarrhoea, fever or persistent cough each reduced weight gain.
      Catch-up in weight then took up to 8 months, probably because of the poor
      nutritional quality of supplementary feeds. The incidences of local traditional
      operations in the first year were: circumcision 63% in males and 4% in females,
      uvulectomy 35% and the extraction of milk teeth 38%. Although circumcision had no
      detectable adverse effect on weight, uvulectomy and milk teeth extraction both
      reduced weight gain.

PMID- 9620570
TI  - 'Back to sleep': the position in Oxfordshire and Northampton.
AB  - We examined hospital and domestic infant care practices in Oxfordshire and
      Northampton Health Districts to measure changes in prevalence of sudden infant
      death syndrome (SIDS) risk factors, and to evaluate a specific educational
      intervention restricted to Oxfordshire. We sent a postal questionnaire to 2781
      parents of babies newly born in January 1992, July 1992 and January 1993 and
      achieved an 88% response rate. Overall, in hospital a relatively constant
      proportion (81%) slept on their sides and few prone, whereas at home 52% (but
      increasing) slept supine and 8% prone part or all of the time. Significant
      differences existed by district, both in hospital and at home, with more sleeping
      supine in Oxfordshire and more side-sleeping/propping in Northampton. First-time
      parents were more receptive to safety guidelines about sleeping position and
      several other risk factors also. We detected no modifying effect of the
      Oxfordshire advice. Professional practice can influence parental behaviour but
      general media coverage may produce the biggest effects.

PMID- 9620571
TI  - Visual impairment in children: prevalence, aetiology and care, 1976-85.
AB  - Visual impairment (corrected visual acuity in the best eye < 0.3) was evaluated
      in a retrospective study of 296 children born between 1976 and 1985 and recruited
      from three French departments. For children younger than 9 years, the overall
      prevalence was 0.80 per 1000 and that of blindness was 0.28 per 1000. No decrease
      in prevalence was noted over this decade. The most common aetiologies were
      antenatal factors (48%), which were observed mainly in the cases of poor vision,
      and perinatal factors (27%), which were more common in the cases of blindness.
      Fifty-six per cent of the children had an additional severe handicap. The most
      common association was with motor impairment and mental retardation. The mean age
      of first medical care (3.1 years) did not change over the decade: 2.0 years for
      children with an associated handicap, 2.9 years for cases of isolated blindness
      and 5.1 years for cases of isolated poor vision. Among children with isolated
      visual impairment, there was a significantly higher percentage of scholastic
      underachievers in those presenting after the age of 5 years (39.3% vs. 14.6%).

PMID- 9620572
TI  - Anti-idiotype monoclonal antibodies against anti-microcystin antibody and their
      use in enzyme immunoassay.
AB  - Microcystins (MCs), a group of heptapeptide hepatotoxins produced by
      cyanobacteria, are suspected as tumor-promoter contaminants of environmental
      water. We have previously developed an enzyme-linked immunosorbent assay (ELISA)
      for MCs based on an anti-MC MAb (MAb-mc). We describe here the production of anti
      idiotype MAbs (MAb-ids) which react with MAb-mc and their use in a new ELISA for
      MCs. For the production of MAb-id, hybridoma cells were generated from mice
      immunized with MAb-mc. Two MAbs were selected for their ability to inhibit the
      binding of MAb-mc to microcystin-LR (MCLR)-bovine serum albumin conjugate in
      ELISA. The one with the higher inhibitory activity, designated Id7 (IgG1, kappa),
      was further characterized. ELISA and immunoprecipitation analysis revealed that
      Id7 specifically bound to MAb-mc but not to control IgG1, and the binding was
      inhibited by free MCLR. Therefore, Id7 is a MAb-id to MAb-mc and potentially
      possesses the structural image of MCLR. To establish MAb-id based ELISA, Id7 was
      tested for use in three types of competitive ELISA for MCs. The best format
      enabled reliable measurements of MCLR in the range of 100-1000 pg/ml with a
      coefficient of variation of less than 3%. In addition, microcystin-RR and
      microcystin-YR, principal MCs found in environmental water, were cross-reacted
      well (67-111% of MCLR) in the ELISA although 6(Z)-MCLR, a minor component, was
      less reactive (7% of MCLR). A comparative study of the MAb-id based ELISA with
      previously established MAb-mc based ELISA revealed good correlation (n = 14, r =
      0.97) between the two methods for measurements of MCs content in freshwater
      samples. Thus, developed MAb-id based ELISA is an useful alternative for
      environmental monitoring of MCs.

PMID- 9620573
TI  - First report of microcystins in Taiwan.
AB  - This is the first report on microcystins from Microcystis aeruginosa Kutzing in
      Taiwan. A total of nine strains of cyanobacteria have been isolated from
      eutrophic aquaculture ponds and water reservoirs. By mouse toxicity assay, six of
      the nine strains had LD100 in the range of 25-100 mg per kg mouse for dried
      bacterial mass. Microcystin-LR and -RR were found in all toxic strains and their
      contents ranged from 0.11-10.06 microg and 0.08 2.21 microg per mg of dried
      bacteria, respectively. Microcystin-RA, a minor component found only in M. TN-2
      and M. CY-1 strains, was identified as a new microcystin. All three toxins were
      isolated by a serial separation on an LH-20 column, Si-flash column
      chromatography and reverse phase HPLC. Toxins were further identified by
      comparing their FABMS, 1H and 1H-1H COSY NMR spectra with the authentic
      microcystin-LR. Several other microcystin-like compounds were also found in the
      cultured strains and their structures are being determined.

PMID- 9620574
TI  - Purification and variability in thrombin-like activity of Bothrops atrox venom
      from different geographic regions.
AB  - Bothrops atrox snake venoms from two different Amazon regions, i.e., Manaus, AM
      (3 degrees 0.6'40"S; 60 degrees 0.1'6.0"W) and Tucurui, PA (3 degrees 0.42'30"S;
      49 degrees 0.41'45"W), were analyzed with respect to the thrombin-like activity
      component by elution profile on gel-filtration and reverse phase HPLC
      chromatography, electrophoretic mobility on SDS-PAGE, and enzymatic activity on
      fibrinogen. Despite some individual discrepancies among venom specimens, the
      thrombin-like activity present in the Manaus pool was eluted earlier compared
      with the Tucurui pool but its enzymatic specific activity on thrombin was lower
      (s.a. = 6.0) than that observed in the Tucurui pool (s.a. = 134.0). However, the
      electrophoretic mobilities of the pools were similar, with most protein bands
      being concentrated around three main regions, i.e., protein bands with an
      apparent mr of 100 kDa, of 38-37 kDa and 30 kDa. However, no significant
      differences were observed in amidolytic activity on the synthetic substrate Tos
      Gly-Pro-Arg-pNa, and there was no correlation between thrombin-like and
      amidolytic activities. A 32 kDa protein endowed with thrombin-like activity and
      specific activity of 2444 recognized and neutralized by horse anti-B. atrox
      antivenom, was purified by the successive use of gel filtration, electrofocusing
      and reverse phase HPLC.

PMID- 9620575
TI  - Toxicity of sea nettle toxin to human hepatocytes and the protective effects of
      phosphorylating and alkylating agents.
AB  - The sea nettle jellyfish toxin (SNTX), which contains several polypeptides, was
      highly toxic to human hepatocytes. The Cytosensor microphysiometer was used
      continuously to monitor cell media acidification rate as an index of cellular
      metabolic activity. Cells exposed to > 1 microg SNTX protein/ml media exhibited a
      transient increase in metabolic activity, followed by a sharp decrease and cell
      death within minutes. The kinetics of the transient increase and subsequent
      decline increased with higher concentrations of SNTX. The biphasic and time
      dependent response of hepatocytes to SNTX suggests that more than one mechanism
      may be involved in the toxicity of its different polypeptides. SNTX-induced
      cytotoxicity of hepatocytes was reduced by the presence of high titer antibodies
      against a heterologous jellyfish. Phenobarbital-induced cells became more
      vulnerable to SNTX, suggesting that some toxin component(s) require(s)
      bioactivation. Short-term exposure (1-2 h) to 10 microg/ml of the calcium
      ionophore calcimycin, or the non-selective monovalent cation ionophore
      gramicidin, had no effect on metabolic activity. However, 165 microg/ml
      gramicidin or 53 microg/ml calcimycin produced slight transient activation
      followed by steady decline in metabolic activity, while 20 h exposure to either
      ionophore produced total cell death. Exposure to even a 10-fold lower
      concentration of either ionophore killed 88% and 75%, respectively. This
      contrasts with the toxicity of SNTX which is detectable in minutes with as little
      as 3 microg/ml. Since pre-exposure to the organophosphate anticholinesterases VX
      and paraoxon, or the chemotherapeutic alkylating agents cyclophosphamide and
      mechlorethamine reduced the cytotoxic effects of SNTX, it suggests that
      phosphorylation or alkylation of cell protein(s) interferes with SNTX toxicity.

PMID- 9620576
TI  - Comparative analyses by HPLC and the sodium channel and saxiphilin 3H-saxitoxin
      receptor assays for paralytic shellfish toxins in crustaceans and molluscs from
      tropical North West Australia.
AB  - The increased frequency and distribution of red tides requires the development of
      high-throughput detection methods for paralytic shellfish toxins (PST). Community
      ethics also requires that there be a reduced reliance upon the standard mouse
      bioassay. A biomolecular assay such as the sodium channel 3H-saxitoxin binding
      assay can satisfy both of these requirements but may be compromised by cross
      reactivity with the structurally unrelated tetrodotoxins (TTX). This study
      utilised the sodium channel assay but also an alternative 3H-saxitoxin binding
      assay based upon a saxiphilin isoform from the centipede Ethmostigmus rubripes to
      screen for PSTs. Saxiphilin is a novel transferrin which binds saxitoxin (STX)
      but differs from the sodium channel in not having any measurable affinity for
      TTX. A detailed analysis of toxin composition was achieved by high performance
      liquid chromatography (HPLC). Various crustaceans and molluscs accumulate PSTs
      and TTX, thus proving useful biomarkers for these toxins in their immediate
      environment and an ideal challenge to the detection and analysis of PSTs in this
      presumptive screening program. Also, there has been little investigation of PSTs
      in invertebrates from the Indian Ocean so this region was selected to extend our
      knowledge of the distribution of these toxins. 190 crabs and shellfish
      encompassing 31 species were collected from reefs along the North-West Australian
      coast and tested for PSTs and TTX by sodium channel and saxiphilin bioassays as
      well as HPLC. PSTs were detected in 18 species of crabs and shellfish of the 31
      species tested. Eight of these species have not been previously described as
      toxic, these being the crabs Euzanthus exsculptus, Lophozozymus octodentatus,
      Metopograpsus frontalis, Pilumnus pulcher, Platypodia pseudogranulosa and
      Portunus pelagicus, and the molluscs Tectus fenestratus and Trochus hanleyanus.
      By HPLC, only one or both of STX and decarbamoyl-STX was detected in any extract.
      Some extracts markedly inhibited 3H-saxitoxin binding by the sodium channel but
      not by saxiphilin. The close agreement between toxin quantification by the PST
      specific methods of HPLC and the saxiphilin bioassay is indicative that the
      additional toxicity detected by the sodium channel assay is TTX.

PMID- 9620577
TI  - Synopsis of recent developments in venomous snake systematics, No. 2.
AB  - Developments in our understanding of the systematics of venomous snakes since the
      beginning of 1996 are discussed and reviewed with special emphasis on their
      relevance and implications for toxinologists and clinicians. Groups of snakes
      affected by recent developments include the genera Elapomorphus, Rhabdophis,
      Vermicella, Atheris, Daboia, Agkistrodon/Gloydius, Bothrops/Bothriopsis and
      Trimeresurus. Other important publications on venomous snakes are noted.

PMID- 9620578
TI  - Indian red scorpion (Buthus tamulus) venom-induced augmentation of cardiac
      reflexes is mediated through the mechanisms involving kinins in urethane
      anaesthetized rats.
AB  - The mechanism underlying the action of Indian red scorpion (Buthus tamulus; BT)
      venom on cardiac reflexes was examined in urethane anaesthetized adult albino
      rats of either sex. Intravenous injection of phenyldiguanide (PDG) produced
      reflex hypotension, bradycardia and apnea lasting for > 60 s. The PDG-induced
      reflex responses (blood pressure, heart rate and respiration) were augmented
      greatly (magnitude and time period) after exposure to BT venom (100 microg/kg,
      i.v., for 30 min). However, there were no great alterations in resting blood
      pressure, heart rate and respiratory rate. Pretreatment with kallikrein kinin
      inhibitor (aprotinin; 6000 kallikrein inactivating unit, i.v.) blocked the BT
      venom-induced augmentation of PDG reflex response. Further, pretreatment with
      indomethacin (prostaglandin synthetase inhibitor; 10 mg/kg) and heparin (1000
      units/kg) also blocked the venom-induced potentiation of the reflex. Captopril
      (15 mg/kg), an agent known to increase endogenous kinins, also augmented the PDG
      induced-reflex to the same extent as in BT envenomed rats. The captopril-induced
      augmentation of the reflex was blocked by aprotinin and heparin, but not by
      indomethacin. The results indicate that kinins and prostaglandins are involved in
      the BT venom-induced augmentation of the cardiac reflexes.

PMID- 9620579
TI  - Inhibition by CaNa2EDTA of local tissue damage induced by Bothrops asper
      (terciopelo) venom: application in horse immunization for antivenom production.
AB  - The ability of the chelating agent CaNa2EDTA to inhibit local tissue damage
      induced by Bothrops asper venom was studied in mice and in horses used for
      polyvalent (Crotalinae) antivenom production. CaNa2EDTA was devoid of toxicity
      when injected i.m. or s.c. inducing only a mild edema. Preincubation of B. asper
      venom with CaNa2EDTA inhibited hemorrhagic and dermonecrotic activities, but did
      not reduce edema-forming and myotoxic effects. A group of horses initially
      immunized with native venoms developed less severe local tissue reactions when
      injected with booster doses of venom and CaNa2EDTA than when receiving booster
      injections of venom alone, although they showed a similar antivenom response.
      Moreover, antivenoms produced from plasmas of horses that received booster
      injections of either venom alone or venom plus CaNa2EDTA had similar neutralizing
      activity against lethal, hemorrhagic and coagulant effects induced by B. asper
      venom. The similar antibody response was corroborated by Western blotting using
      crude venom and by an ELISA that estimates anti-myotoxin titer. It is concluded
      that the chelating agent CaNa2EDTA reduces the extent of local tissue damage
      induced by B. asper venom, without affecting the immune response of horses
      against pharmacologically-relevant venom components.

PMID- 9620580
TI  - In vivo protection against Tityus serrulatus scorpion toxins by immunization of
      mice with a non-toxic protein.
AB  - The possibility of inducing a humoral immune response able to produce
      neutralizing antibodies against the lethal effects of scorpion toxins was
      evaluated in the mouse model. A non-toxic protein (TsNTxP) was purified from the
      venom of the Brazilian scorpion Tityus serrulatus by combining gel filtration,
      ion exchange and reverse phase HPLC chromatographic steps. After four injections
      of TsNTxP the mice developed an IgG response. The anti-TsNTxP antibodies had a
      comparable high cross-reactivity for the crude venom, toxic fraction (toxic
      fraction of venom that represents most of the toxicity of the crude venom --
      TsTFG50) and TsIV, a representative alpha-type toxin of T. serrulatus, and
      moderate binding capacity for TsVII, a representative beta-type toxin. In vitro
      neutralization assays indicated that preincubation of a lethal dose of the toxic
      fraction with immune serum strongly reduced its toxicity. In vivo protection
      assays showed that mice immunized with TsNTxP resisted a challenge of 10 LD50
      (s.c.) of the toxic fraction of T. serrulatus venom.

PMID- 9620581
TI  - Comparison and characterization of the venoms of three Parabuthus scorpion
      species occurring in southern Africa.
AB  - Parabuthus transvaalicus, P. granulatus, and P. villosus are three medically
      important scorpion species occurring in southern Africa which can cause severe
      envenoming among people. In contrast to many other genera, no data is available
      on the venom composition of scorpions belonging to the genus Parabuthus. Here we
      have investigated the components which may contribute to the venomous potential.
      The constancy of venom composition within each of the three species and between
      the three species was investigated by means of gel filtration chromatography. The
      venoms of the three species each were characterized by a constant and typical
      elution pattern, resulting in a 'gel filtration fingerprint' which allows
      distinction between each species. It appears that certain components in the
      venoms are common to either all three species, or to two of the three species.
      This points to a clear interspecies relationship within the genus. We also
      describe the isolation and characterization of some of the polypeptide toxins
      present in the venoms of P. villosus, P. transvaalicus and P. granulatus by means
      of reversed phase chromatography and screening of the toxic components on voltage
      activated potassium and sodium channels. Our results confirm that toxins which
      inhibit potassium channels and alter sodium channel gating are present in the
      venoms studied.

PMID- 9620582
TI  - Cytotoxic effects of arthropod venoms on various cultured cells.
AB  - The action of arthropod venoms is important to predators in search of prey and to
      humans as incidental victims or as a source for pharmacologically active
      compounds. Venoms from 30 arthropods (including 26 spider species) were assessed
      for cytotoxicity using cultured cells from one insect (Sf9) and three mammalian
      (murine neuroblastoma and macrophages and human osteosarcoma) sources. The most
      cytotoxic venoms to the four cell lines were from predatory jumping spiders
      (Salticidae, Phidippus sp.) and a centipede (Scolopenra sp.), with concentrations
      for 50% response of 1-8 microg venom per ml. The cytotoxicity of Phidippus ardens
      venom at these levels was instantaneous and evidenced by dramatic disruption of
      cell membranes resulting in cell collapse.

PMID- 9620583
TI  - [Snake bite accidents in children in Costa Rica: epidemiology and determination
      of risk factors in the development of abscess and necrosis].
AB  - A retrospective epidemiological analysis is presented of 80 snakebites in
      children admitted to the Pediatrics Service of Tony Facio Hospital in Limon,
      Costa Rica, between 1985 and 1995. An overall incidence rate of 20 snakebite
      accidents per 100,000 inhabitants per year was calculated for the region in that
      period. However, a higher incidence was described in some counties (36 and 30
      cases per 100,000 inhabitants in Talamanca and Siquirres, respectively). Most of
      the cases occurred in February and November, between 16:00 and 19:00 hr. The mean
      age of the affected children was 8.67 +/- 2.66 years. No significant difference
      was found between genders. Thirty-three children affected (41.2%) were members of
      the local indigenous groups and 31 (38.8%) were residents of Talamanca County.
      The species of snake responsible were identified in 58.4% of cases, with Bothrops
      asper being the most important. The lower extremities were the most important
      primary site affected (86.3%). The most common clinical complications described
      in the study group were abscess formation (11.25%), necrosis (10%), renal failure
      (3.75%), compartmental syndrome (2.5%) and anaphylactic shock (1.25%). The
      overall mortality was 2.5%. Statistical analysis of the risk factors relating to
      the two most common complications showed that the condition of coming from
      Talamanca County (P = 0.02), damage in the proximal extremities (P = 0.02), a
      prothrombin time < 2% (P = 0.01) and serum fibrinogen levels < 100 g/dl (P =
      0.01) were risk factors for the development of abscesses. The grade of severity
      of the snakebite (P = 0.018) and serum fibrinogen levels < 100 g/dl were
      associated with development of necrosis. All of the patients with necrosis and
      abscesses also experienced two or more of the risk factors that correlated with a
      sensitivity of 100% and a specificity of 67% for the development of abscess, and
      87% sensitivity and 88% specificity for necrotic complications. According to
      these data, snakebite complications are a relevant health problem in Costa Rica.

PMID- 9620584
TI  - Evidence that histamine is the principal pharmacological component of venom from
      an Australian wolf spider (Lycosa godeffroyi).
AB  - Wolf spiders are common throughout Australia and have been known to cause severe
      reactions in both animals and humans. However, little work has been done on the
      pharmacological activity of Australian lycosids. The purpose of this study was to
      obtain a preliminary pharmacological profile of the venom from an Australian wolf
      spider (Lycosa godeffroyi). The venom caused dose-dependent contractions of
      guinea-pig isolated ileum (1-4 microg/ml), endothelium-dependent relaxation in
      rat isolated aortae (10 microg/ml), a decrease in mean arterial blood pressure in
      the anaesthetised rat (100 microg/kg, i.v.) and an increase in insufflation
      pressure in the anaesthetised guinea-pig (50 microg/kg, i.v.). All of these
      responses were significantly inhibited by the H1-receptor antagonist mepyramine
      at concentrations that selectively inhibited responses to histamine. Venom (5
      microg/ml) caused a decrease in twitch height of the rat stimulated (0.3 msec,
      0.2 Hz, 100 V) vas deferens (prostatic segment). A fluorometric assay for
      histamine detected a concentration of 44.5 ng/microg venom protein. It appears
      that the in vitro and in vivo activity of L. godeffroyi venom observed in the
      present study is due to the presence of histamine.

PMID- 9620585
TI  - Heat and motion stability of polyvalent Crotalidae antivenin, ovine Fab.
AB  - This study was conducted to test the hypothesis that a Fab-based crotalid
      antivenin (FabAV) in commercially packaged vials will remain effective under more
      extreme heat and motion conditions than would be expected in field settings.
      Vials containing FabAV were subjected to heat or motion. The effect of heat or
      motion on the ED50 of FabAV was determined using a mouse model of crotalid snake
      envenomation. The ED50 for the heat stability groups (expressed as a ratio of mg
      antivenin to mg venom) were as follows: 4 degrees C x 60 days (control) = 26.5,
      70 degrees C x 60 days = 66.3, 70 degrees C x 30 days = 52.4, 50 degrees C x 60
      days = 25.8, 50 degrees C x 30 days = 34.0. The ED50 for the two motion stability
      groups were similar: 4 degrees C x 60 days = 40.3 and 70 degrees C x 60 days =
      48.3. These results indicate that FabAV is heat stable at 50 degrees C for 60
      days, but had less potency when heated to 70 degrees C for 30 days. FabAV appears
      less potent after agitation, but remains effective in the mouse model. We
      conclude that FabAV can be safely stored for at least 60 days without
      refrigeration under most field conditions where snake envenomation may occur.

PMID- 9620586
TI  - Combined use of analytical high-performance liquid chromatography and cell
      morphology transformation assay to detect new protein phosphatase inhibitors of
      okadaic acid type.
AB  - The search for new protein phosphatase inhibitors in shellfish contaminated by
      toxin-producing dinoflagellates generally relies on preliminary separation
      techniques followed by biological tests. To detect such substances without
      purifying them initially, we developed an approach based on a correlation of the
      results of two different analytical techniques applied to toxic extracts: high
      performance liquid chromatography after derivation of the toxins and the cell
      morphology transformation assay on KB cells. Application of this protocol to
      stored frozen mussels showed a decrease in okadaic acid concentration during
      storage, with formation of degradation derivatives, some of which possessed
      notable protein phosphatase inhibition activity.

PMID- 9620587
TI  - Endotoxemic-like shock induced by Loxosceles spider venoms: pathological changes
      and putative cytokine mediators.
AB  - The systemic symptoms, tissue lesions and release of cytokines were analysed in
      four isogenic mouse strains with distinct haplotypes injected with various doses
      of Loxosceles intermedia spider venom. The estimated LD50 were 24.5 microg for
      C57Bl/6, 17.6 microg for BALB/c, 6.3 microg for C3H/HeJ and 4.6 microg for A/Sn
      mice. Prostration, acute cachexia, hypothermia, neurological disorders and
      hemoglobinuria were the signals preceding death. Accumulation of eosinophilic
      material inside the proximal and distal renal tubules and acute tubular necrosis
      were the most common histopathological findings. Death was prevented by previous
      treatment of venom with specific antivenom serum. The protein F35 purified from
      the whole venom retained the ability to induce the symptoms of the whole venom.
      The cytokines tumor necrosis factor (TNF), interleukins IL-6 and IL-10 and the
      radical nitric oxide were detected in serum at different levels after venom
      injection. These findings indicate that the state of shock produced in mice by
      whole endotoxin-free L. intermedia venom or by its purified fraction, protein
      F35, mimics the endotoxemic shock, that susceptibility to the systemic effects of
      the venom varies among mice of different haplotypes and that the pattern of in
      vivo cytokine release resembles that of endotoxemic shock.

PMID- 9620588
TI  - Thalassophryne nattereri fish venom: biological and biochemical characterization
      and serum neutralization of its toxic activities.
AB  - Envenomation by Thalassophryne nattereri fishes are an important medical problem
      in northeast of Brazil, causing in human victims considerable pain and edema
      followed by necrosis. Venom obtained from fresh captured specimens of this fish
      was tested in vitro or in animal models for a better characterization of its
      toxic activities. Intradermal injection of the venom in the foot pad of mice
      induced local edema and hemorrhage followed a few hours later by necrosis.
      Subcutaneous injection of the venom induced systemic effects consisting in
      jerking motions, paralysis of hind limbs, erection of hair, rotational movements
      and violent convulsions followed by death. Dead animals showed hyperemia of the
      small intestine and lungs. The venom showed distinct edematous, necrotizing and
      hemolytic activities, a low level of hemorrhagic, myotoxic and proteolytic
      activities and no detectable phospholipase A2 activity. SDS-PAGE analysis of the
      crude venom showed at least 17 components with the major band located around Mw =
      19,000. Almost all proteins stained by amido black were also revealed by Western
      blotting with antibodies to T. nattereri venom. Fractionation of the venom by
      either gel filtration or cation exchange chromatography resulted in a few
      distinct peaks but in both situations the biological activities were located in
      only one of the peaks which corresponded to basic proteins with approximately Mw
      = 47,000. Heating of the venom at 56 degrees C for 60 min completely destroyed
      its biological activities. All venom toxic activities except edema were
      completely neutralized after in vitro incubation with anti-T. nattereri serum.

PMID- 9620589
TI  - Apparent paralytic shellfish poisoning in captive herring gulls fed commercial
      scallops.
AB  - This report describes an acute poisoning event observed in captive herring gull
      (Larus argentatus) chicks fed a batch of store-bought scallops. They developed a
      characteristic acute syndrome, that has not hitherto been reported in birds and
      the cause of which remains to be identified. We suggest that it is a variant of
      paralytic shellfish poisoning (PSP) insofar as it was paralytic and caused by
      shellfish. However, analyses by the U.S. Food and Drug Administration to identify
      known toxins (saxitoxins, brevetoxins, domoic acid) in the scallops were
      negative.

PMID- 9620590
TI  - Development of a bioassay employing the desert locust (Schistocerca gregaria) for
      the detection of saxitoxin and related compounds in cyanobacteria and shellfish.
AB  - Monitoring paralytic shellfish toxins (PST) in shellfish and freshwater
      cyanobacteria is largely dependent on the mouse bioassay. An alternative assay
      was devised using the desert locust Schistocerca gregaria. The bioassay
      successfully identified the optimum extraction procedure for PST from
      cyanobacterial cells and was also suitable for screening acid extracts of
      shellfish flesh. These results demonstrate the potential of the locust bioassay
      for the routine screening of PST in a range of sample matrices.

PMID- 9620591
TI  - Comparison of antihemorrhagic activities in skeletal muscle extracts from various
      animals against Bothrops jararaca snake venom.
AB  - Antihemorrhagic activities of skeletal muscle extracts from various animals were
      compared in inhibiting the hemorrhagic activity of Bothrops jararaca venom. The
      muscle extracts of the European hedgehog (Erinaceus europaeus) exhibited the
      strongest activity, followed by those of other insectivores such as the shrew
      (Crocidura russula) and mole (Talpa europaea). The antihemorrhagic activities of
      muscle extracts from experimental animals such as mice, rats, guinea-pigs,
      hamsters and rabbits were negligible.

PMID- 9620592
TI  - Regulatory CD4 T cells: expression of IL-2R alpha chain, resistance to clonal
      deletion and IL-2 dependency.
AB  - We recently characterized a CD4+ T cell population expressing the IL-2R alpha
      chain (CD25), producing IL-10 and resisting clonal deletion induced by viral
      superantigen (vSAG) encoded by mouse mammary tumor virus [MMTV(SW)]. We now
      report that these apoptosis-resistant cells are generated in the thymus but not
      from the immature CD4+ CD8+ thymocytes. They migrate from the thymus and are
      found in the periphery from at least the 10th day of life, after which they
      expand with the same kinetics in normal and MMTV(SW)-infected mice. Their strong
      capacity for expansion in the periphery makes this population insensitive to
      thymectomy in adulthood. CD4+ CD25+ cells were totally dependent on exogenous IL
      2 for growth in vitro and in vivo, and were missing in IL-2 knockout (KO) mice.
      The absence of this population and/or an inability to produce IL-10 may be the
      missing link between IL-2R alpha KO, IL-2 KO and IL-10 KO mice, which all die of
      inflammatory bowel disease.

PMID- 9620593
TI  - Molecular characterization of rat NKR-P2, a lectin-like receptor expressed by NK
      cells and resting T cells.
AB  - The gene for a rat NK lectin-like receptor (NKLLR), named NKR-P2, has been cloned
      and characterized. Sequence analysis shows that it represents the orthologue of
      human NKG2D and that the two molecules form a distinct NKLLR family, no more
      related to NKG2A/B, -C or -E than to other NKLLR families. Nkrp2 is a single-copy
      gene containing seven introns, mapping to the rat NK gene complex. Rat NKR-P2
      differs from the human orthologue in that its cytoplasmic tail contains 13
      additional amino acids, encoded by a separate exon. Splice variants lacking this
      exon were not detected in T cells or NK cells. NKR-P2 is strongly expressed by NK
      cells. In contrast to other NKLLR, it is also strongly expressed by resting
      thoracic duct CD4+ and CD8+ T cells, but not by thymocytes or other hemopoietic
      cells.

PMID- 9620594
TI  - High-dose oral tolerance prevents antigen-induced eosinophil recruitment into the
      mouse airways.
AB  - We have previously shown that antigen-induced eosinophil recruitment into the
      tissue of sensitized mice is mediated by CD4+ T cells and IL-5. To determine
      whether the induction of oral tolerance down-regulates antigen-induced eosinophil
      recruitment into the tissue, we studied the effect of oral administration of a
      protein antigen on antigen-induced eosinophil infiltration in the trachea of
      sensitized mice, on antigen-induced CD4+ T cell infiltration and IL-5 production
      in the airways, and on the in vitro production of IL-2, IL-4, IL-5 and IFN-gamma
      in spleen cells of the mice. Oral administration of a protein antigen in high
      doses inhibited antigen-induced eosinophil infiltration in the trachea and IgE
      antibody production in mice in an antigen-specific manner. The oral
      administration of antigen also suppressed both CD4+ T cell recruitment into the
      trachea and IL-5 levels in the bronchoalveolar lavage fluids of the mice after
      antigen inhalation. In vitro antigen-induced production of IL-2, IFN-gamma, IL-4
      and IL-5 was decreased in spleen cells of antigen-fed mice, indicating the
      induction of both Th1 and Th2 cell tolerance in vivo. On the other hand,
      pretreatment with anti-transforming growth factor-beta antibody at the time of
      immunization with antigen had no significant effect on the inhibition of antigen
      induced eosinophil recruitment and IgE antibody production in antigen-fed mice.
      Finally, antigen-specific CD4+ T cells were not deleted in TCR transgenic mice
      after antigen feeding by FACS analysis. Taken together, these results indicate
      that high-dose oral tolerance induces not only Th1 but also Th2 cell tolerance in
      vivo and thereby inhibits antigen-induced eosinophil recruitment into the tissue.

PMID- 9620595
TI  - Molecular characterization of the low-affinity IgE receptor Fc epsilonRII/CD23
      expressed by human eosinophils.
AB  - CD23/Fc epsilonRII, the low-affinity receptor for IgE, is a pluripotent molecule
      with pleiotropic effects on cell activation and proliferation, antigen
      presentation and IgE synthesis. Initial investigations have suggested that CD23
      expression was restricted to B lymphocytes and macrophages, but a much wider cell
      distribution is now acknowledged. Despite experimental evidence suggesting that
      human eosinophils could express the low-affinity IgE receptor Fc epsilonRII/CD23
      with biological functions, no molecular cloning data have been reported until
      now. Whereas in situ hybridization confirmed the expression of CD23 mRNA in
      eosinophils, RT-PCR analysis of human eosinophil cDNA derived from a cDNA library
      revealed the presence of CD23, totally homologous with the CD23 a and b
      sequences. Eosinophils from different hypereosinophilic patients as well as the
      eosinophilic leukemia cell line EoL-3, analyzed by RT-PCR, expressed both CD23 a
      and b isoforms. In situ RT-PCR confirmed that mRNA corresponding to CD23 a and b
      isoforms was detected in human eosinophils. Finally, immunocytochemistry allowed
      us to show a differential expression of Fc epsilonRII/CD23 and Fc epsilonRI by
      subpopulations of eosinophils, with a preferential expression of Fc
      epsilonRII/CD23 in the hypodense population. These results provide definitive
      evidence that the low-affinity IgE receptor (Fc epsilonRII) synthesized by human
      eosinophils is identical to the CD23 molecule expressed on B cells, and that the
      two CD23 isoforms a and b can be expressed by eosinophils.

PMID- 9620596
TI  - Absence of TNFRp55 influences virus-induced autoimmunity despite efficient
      lymphocytic infiltration.
AB  - Tumor necrosis factor (TNF)-alpha is a multipotent cytokine associated with many
      cellular functions, including inflammation and anti-viral defense. Many studies
      have implicated TNF-alpha in the pathogenesis of autoimmune diseases. TNF-alpha
      responses are mediated through binding to specific cell surface receptors,
      TNFRp55 and TNFRp75. The objective of the present study was to investigate the
      contribution of the TNFRp55 in the inflammatory response associated with
      autoimmune diabetes development in a viral transgenic model. In this model, the
      animals express lymphocytic choriomeningitis virus (LCMV)-glycoprotein (gp) in
      the beta cells of the pancreas under the control of the rat insulin promoter (RIP
      gp). Diabetes is induced following LCMV infection due to beta cell destruction by
      LCMV-specific CD8+ cytotoxic T lymphocytes. TNFRp55-deficient RIP-gp animals were
      examined to assess the importance of the TNFRp55. The kinetics and onset of
      lymphocytic infiltration into the pancreatic islets and hyperglycemia was not
      altered in the absence of TNFRp55 after LCMV infection. Animals were evaluated
      following recombinant LCMV-gp vaccinia virus infection to test whether properties
      of the infectious agent influence autoimmunity. Interestingly, the kinetics were
      accelerated and the frequency of diabetes was increased in TNFRp55-deficient mice
      compared with control animals. This accelerated onset of diabetes is likely a
      result of increased viral replication in the TNFRp55-deficient host. Thus, these
      data demonstrate that TNFRp55 is not essential for producing the local
      inflammatory effects which contribute to organ-specific autoimmunity in this
      transgenic model. However, the absence of TNFRp55 altered the kinetics and
      incidence of the disease in a pathogen-dependent fashion.

PMID- 9620597
TI  - Development of hapten-induced IL-4-producing CD4+ T lymphocytes requires early IL
      4 production by alphabeta T lymphocytes carrying invariant V(alpha)14 TCR alpha
      chains.
AB  - This paper investigates the mechanisms responsible for the generation of IL-4
      producing CD4+ T cells during contact sensitization with the hapten
      trinitrochlorobenzene (TNCB). Lymph node cells taken 1 day after immunization
      spontaneously released IL-4 while lymph node cells taken 2 and 3 days after
      immunization did not produce IL-4. A second wave of IL-4 production that was both
      antigen-specific and MHC class II (I-A)-restricted was observed 4 days after
      immunization. The spontaneous release of IL-4 at day 1 was due to the alphabeta+
      double-negative (CD4- CD8-) T lymphocytes that also expressed NK1.1 and showed
      V(alpha)14 rearrangement, while alphabeta+ CD4+ T lymphocytes were the source of
      the antigen-specific IL-4 production at day 4. Early IL-4 production was required
      for the development of IL-4-producing CD4+ T cells as mice injected with anti
      V(alpha)14 or anti-IL-4 mAb produced little IL-4 and IL-10, while production of
      IFN-gamma was increased approximately 2-fold. These results indicate that the
      development of IL-4-producing CD4+ T lymphocytes in the TNCB system requires
      early production of IL-4 by alphabeta+ double-negative cells carrying invariant
      V(alpha)14 TCR alpha chain.

PMID- 9620598
TI  - Identification of mimotopes for the H4 minor histocompatibility antigen.
AB  - The H4 minor histocompatibility antigen (HA) of mice includes a single
      immunogenic peptide presented by H-2Kb molecules that stimulates skin allograft
      rejection and is immunodominant in the stimulation of cytolytic T lymphocytes
      (CTL) specific for multiple minor HA. We have identified H4 mimotopes that are
      recognized by the H4-specific M9 CTL clone through the use of a random peptide
      library comprised of bacterial clones expressing an inducible fusion protein
      tailed with the octamer sequence SXIXFXXL. Eight discrete mimotopes were
      identified that sensitized RMA-S cells for lysis by M9 CTL down to concentrations
      of 10(-11) M. Comparable reactivity was observed with a short-term, H4-specific
      CTL line indicating that the mimotopes were not solely specific for the selecting
      M9 clone. All mimotopes included Gly at p2 and either Val or Ile at p4,
      suggesting a requirement for a hydrophobic residue with specific conformation.
      All mimotopes included either Arg or His at p7, implicating a requirement for a
      specific positively charged amino acid at that position. The sixth position was
      more variable with four of eight mimotopes having a Val residue with single
      mimotopes including alternative amino acids, the majority of which were
      hydrophobic. Analysis of mimotopes for hydrophobicity and charge by reverse-phase
      HPLC and capillary electrophoresis respectively indicated that (i) mimotopes with
      Val at both p4 and p6 were hydrophobically similar (but not identical) to the
      natural H4 peptide, and (ii) a S --> E substitution at p1 resulted in a peptide
      (EGIVFVRL) with charge characteristics equivalent to those of the natural H4
      peptide.

PMID- 9620599
TI  - Abrogation of autoimmune disease in Lyn-deficient mice by the mutation of the Btk
      gene.
AB  - Lyn and Btk play a critical role in B cell development and intracellular
      signaling. Lyn-deficient mice exhibit splenomegaly, elevated serum levels of IgM,
      production of autoantibody and glomerulonephritis with age. On the other hand,
      xid mice, which carry a point mutation in the btk gene, show a decrease in
      numbers of peripheral mature B cells, reduced serum levels of IgM and IgG3,
      disappearance of CD5+ B-1 cells, and low proliferative response to anti-IgM or
      LPS stimulation in vitro. In order to investigate the interaction between Lyn and
      Btk during B cell development, we established lyn-deficient xid mice. Lyn
      deficient xid mice exhibited greatly reduced numbers of peripheral mature B
      cells, disappearance of CD5+ B-1 cells, markedly reduced serum levels of IgM and
      IgG3, low proliferative response to anti-IgM or lipopolysaccharide stimulation
      and no evidence for autoimmune disease. In addition, splenomegaly in lyn
      deficient mice, which was mainly due to the accumulation of Mac-1+, cytoplasmic
      IgM+ lymphoblast-like cells, was also diminished in lyn-deficient xid mice. Thus,
      immunological abnormalities found in lyn-deficient mice were strongly affected by
      the absence of Btk. The present results suggest that the autoimmune symptoms in
      lyn-deficient mice may be caused by not only the abnormal response of B-2 cells
      but also that of B-1 cells, and that the interaction between Lyn and Btk is
      partly in tandem at the signaling pathway in B cells.

PMID- 9620600
TI  - Glycosyltransferase regulation mediated by pre-TCR signaling in early thymocyte
      development.
AB  - CT1 is a carbohydrate moiety of CD45 that is expressed on fetal thymocytes in
      vivo. Examination of CT1 expression on thymocyte subsets revealed that primarily
      pro-T cells (CD44+ CD25+) and pre-T cells (CD44- CD25+) expressed CT1.
      Interestingly, non-T-lineage committed lymphoid progenitors (CD44+ CD25-) lacked
      CT1 indicating temporal regulation of expression of this determinant in early T
      lineage committed development. In addition, CT1 was expressed by the majority of
      thymocytes in RAG-2(-/-) mice where thymocyte development is blocked at the CD44-
      CD25+ stage. Since late pre-T cells (CD44- CD25-) lacked the CT1 epitope we
      tested whether pre-TCR triggering regulated CT1 expression. Injection of
      CD3epsilon-specific mAb into RAG-2(-/-) mice induces differentiation of immature
      thymocytes to the double-positive stage of thymocyte development. Using this
      system, we demonstrated that expression of CT1 by RAG-2(-/-) thymocytes was
      rapidly lost from pre-T cells following anti-CD3 mAb treatment. Furthermore, the
      decline in CT1 expression induced by CD3 signaling paralleled a loss of mRNA for
      the glycosyltransferase responsible for the addition of CT1 to CD45. Flow
      cytometric analysis also revealed that the loss of the CT1 epitope was inversely
      correlated with an increase in peanut agglutinin ligand expression, demonstrating
      a complex regulation of cell surface glycosylation at a critical juncture in
      thymocyte development.

PMID- 9620601
TI  - The OX-40 receptor provides a potent co-stimulatory signal capable of inducing
      encephalitogenicity in myelin-specific CD4+ T cells.
AB  - The OX-40 receptor, a member of the nerve growth factor/tumor necrosis factor
      receptor gene family, is expressed preferentially on autoreactive CD4+ T cells
      isolated from the site of inflammation in rats with clinical signs of
      experimental autoimmune encephalomyelitis (EAE). To examine whether the OX-40
      receptor has biologic relevance to T cell function, we evaluated the ability of a
      rat OX-40 receptor-specific antibody to co-stimulate a myelin basic protein (MBP)
      reactive CD4+ T cell line. The anti-OX-40 antibody provided a potent co
      stimulatory signal to CD4+ T cells when added in conjunction with a submitogenic
      dose of anti-CD3, but the anti-OX-40 antibody alone did not produce a mitogenic
      response. The magnitude and dose-response of anti-OX-40 co-stimulation was
      virtually identical to the signal delivered to T cells when cultured with anti
      CD28 in conjunction with anti-CD3. MBP-specific T cells stimulated with both anti
      CD3 and anti-OX-40 antibodies expressed increased mRNA and protein for IL-2 when
      compared to anti-CD3 alone. MBP-specific T cells stimulated with both anti-CD3
      and anti-OX-40 antibodies were also able to induce EAE when transferred into
      naive Lewis rats. In contrast, cells stimulated with anti-CD3 alone were not
      encephalitogenic. These data suggest that the function of the OX-40 receptor on
      activated T cells is to provide an alternative pathway for T cell co-stimulation
      that may be similar in potency to the CD28-mediated signal.

PMID- 9620602
TI  - Differential presentation of endogenously processed cytotoxic T lymphocyte
      epitopes by mouse hepatocarcinoma cell lines induced by SV40 large T antigen.
AB  - Tumor cells can have different morphologic or metabolic phenotypes and display
      genetic instability. Thus they could also vary in their ability to present
      epitopes to the immune system. We have analyzed the presentation of H-2 Kb- and
      Db-restricted cytotoxic T lymphocyte (CTL) epitopes of a tumor-associated antigen
      by three cell lines derived from hepatocarcinomas developed in vivo by mice
      transgenic for SV40 T targeted to the liver. SV40 T is the obvious tumor-specific
      antigen and epitopes derived from this antigen were therefore studied. The study
      included four already known epitopes that can be presented by SV40-transformed
      kidney cells and two new CTL epitopes that were identified in the present work.
      CTL lines specific for each epitope were obtained from C57BL/6 mice and were used
      to map the presentation of SV40 T peptides by the hepatocarcinoma cells. These
      tumor cells were derived from the same tissue, induced by the same agent and all
      naturally presented peptide p232-240 from p53. Despite these common features,
      they all had different patterns of spontaneous presentation of SV40 T CTL
      epitopes. The mechanisms underlying this disparity are discussed, together with
      the possible consequences for establishing immunotherapeutic strategies.

PMID- 9620603
TI  - Signal transduction via a protein associated with a glycosylphosphatidylinositol
      anchored protein, decay-accelerating factor (DAF/CD55).
AB  - Decay-accelerating factor (DAF/CD55) is a glycosylphosphatidylinositol-anchored
      protein which is known to have signal transducing capacity and to be associated
      with several proteins. To determine the signal transducer in the DAF-forming
      complex, we purified DAF-associated proteins from Raji B cells using an anti-DAF
      mAb (1C6)-bound affinity column and established five mAb against them. Among
      these, mAb 2E12-G7(IgM/kappa) reacted with a variety of intact cells, including
      peripheral blood mononuclear cells (PBMC), as well as cells from T and B cell
      lines, as shown by cytofluorimetric analyses. The Mr of 2E12-G7 antigen was
      estimated to be 43 kDa by surface biotinylation and immunoblotting analysis. This
      antigen was demonstrated in 1C6 immunoprecipitates, but not in anti-CD59 (another
      GPI-anchored complement regulatory factor)-immunoprecipitates. Sequential
      treatment with 1C6 F(ab')2 and then with anti-mouse Ig F(ab')2 stimulated PBMC to
      induce tyrosine phosphorylation on proteins of 45, 72, 78 and approximately 100
      kDa. Also, mAb cross-linked to 2E12-G7 stimulated PBMC to induce tyrosine
      phosphorylation on proteins of 72, 78 and approximately 100 kDa. Furthermore,
      when 2E12-G7 and 1C6 immunoprecipitates were incubated with [gamma-32P]ATP, the
      main constituents detected in both were phosphorylated proteins of 26, 32 and 62
      kDa. Thus, DAF-associated 2E12-G7 antigen transduces a signal, similar to the DAF
      molecule.

PMID- 9620604
TI  - Two distinct regions of the CD28 intracytoplasmic domain are involved in the
      tyrosine phosphorylation of Vav and GTPase activating protein-associated p62
      protein.
AB  - The T cell-associated CD28 molecule plays a key role in T cell co-stimulation.
      Its ligation induces the tyrosine phosphorylation of numerous proteins including
      CD28 itself as well as a restricted set of substrates of 97 and 62-68 kDa which
      are poorly phosphorylated by the tyrosine kinases induced by CD3-TCR triggering.
      In this study, we identify these substrates as the product of the vav proto
      oncogene and as a 62 kDa protein that could correspond at least in part to
      p62dok, the 62 kDa adaptor molecule associated to p120 Ras-GTPase activating
      protein. Both p97vav and p62 are tyrosine phosphorylated upon CD28 ligation by
      mAb or by its counter-receptor B7-1/CD80. Using CD28 mutants, we also show that
      Vav and p62 tyrosine phosphorylation is regulated by distinct domains within the
      CD28 cytoplasmic tail: residues 173-181 for Vav and residues 182-202 for p62.
      Finally, the phosphorylation of Vav and p62 does not require an intact binding
      site for Grb-2 or p85 SH2 domains. We thus demonstrate that the CD28 cytoplasmic
      domain contains at least three functionally independent regions involved in CD28
      induced signal transduction, since in addition to the Grb-2 and p85 SH2 domain
      binding site (Tyr173), residues 173-181 and 182-202 are associated with Vav and
      p62 tyrosine phosphorylation respectively.

PMID- 9620605
TI  - CTLA-4 is required for the induction of high dose oral tolerance.
AB  - Mucosal and systemic administrations of high dose antigens induce long-lasting
      peripheral T cell tolerance. We and others have shown that high dose peripheral T
      cell tolerance is mediated by anergy or deletion and is preceded by T cell
      activation. Co-stimulatory molecules B7-1 (CD80)/B7-2 (CD86) and their counter
      receptors CD28/CTLA-4 play pivotal roles in T cell activation and immune
      regulation. In the present study, we examined the roles of the B7 co-stimulation
      pathway in the generation of high dose peripheral T cell tolerance. We found that
      blocking B7:CD28/CTLA-4 interaction at the time of tolerance induction partially
      prevented T cell tolerance, whereas selective blockade of B7:CTLA-4 interaction
      completely abrogated peripheral T cell tolerance induced by either oral or i.p.
      antigens. These results suggest that CTLA-4-mediated feedback regulation plays a
      crucial role in the induction of high dose peripheral T cell tolerance.

PMID- 9620606
TI  - Biased dependency of CD80 versus CD86 in the induction of transcription factors
      regulating the human IL-2 promoter.
AB  - In addition to the signals obtained by ligation of the TCR, T cells need
      additional, co-stimulatory signals to be activated. One such co-stimulatory
      signal is delivered when CD28 on T cells binds to CD80 or CD86 on antigen
      presenting cells (APC). In the present study, we analyzed the ability of CD80 and
      CD86 to co-stimulate human T cells activated by superantigen. Using the Raji B
      cell lymphoma, which express similar levels of CD80 and CD86, it was found that T
      cell proliferation was mainly co-stimulated by CD80. To further characterize the
      consequences of this biased co-stimulatory dependency, we employed a well-defined
      system of transfected CHO cells expressing human MHC class II together with CD80,
      CD86 or CD80 and CD86. Proliferation of freshly prepared CD4+ T cells required
      the presence of either CD80 or CD86. However, IL-2 production reached only
      suboptimal levels in the presence of CD86 but optimal levels with CD80. To
      analyze IL-2 transcriptional activity in CD80 and CD86 co-stimulated T cells we
      used Jurkat T cells transfected with luciferase reporter gene constructs. CD80
      induced higher levels of IL-2 promoter-enhancer activity compared to CD86.
      Furthermore, the activity of transcription factors regulating the IL-2 promoter
      enhancer region including activation protein-1, CD28 response element and nuclear
      factor kappaB were 4-8 times higher after CD80 compared to CD86 ligation. Our
      results suggest that the eventual appearance of CD80 on recently activated CD86+
      APC is important for the superinduction of IL-2 production and to support
      vigorous T cell proliferation.

PMID- 9620607
TI  - Allele-unrestricted presentation of lidocaine by HLA-DR molecules to specific
      alphabeta+ T cell clones.
AB  - T cells recognize peptide and non-peptide antigens. Drugs represent typical
      examples of non-peptide antigens. The majority of drug-specific T cells are
      alphabeta+ TCR T cells and are MHC class I or II restricted. Here we show the
      existence of drug (lidocaine)-specific T cell clones which proliferate in the
      presence of antigen-presenting cells (APC) with different HLA alleles. Two clones
      (SFT24 and E20) were analyzed in detail. They show a narrow dose-dependent
      proliferation to lidocaine, but not to procaine. With the use of a panel of HLA
      typed allogeneic APC, we observed that certain allogeneic APC plus lidocaine lead
      to a similar, others to partial and some to no proliferation of the lidocaine
      specific T cell clones. An APC-independent proliferation could be excluded since
      both clones proliferated only marginally without APC and increasing the number of
      APC resulted in a higher proliferation. Blocking experiments with anti-DP, -DQ
      and -DR antibodies showed that lidocaine is presented in a HLA-DR-restricted way
      both with autologous or allogeneic APC. Mouse fibroblasts transfected with an
      allogeneic HLA-DRB1*01 but not HLA-DR-negative mouse fibroblasts could serve as
      presenting cells. Fixation of APC did not hamper drug presentation, but pulsing
      of APC with the drug was not possible, indicating that processing is not required
      and that lidocaine binds in an unstable way to the MHC-peptide complex. This
      degenerate drug recognition has certain features of superantigen recognition,
      such as the ability of drugs to bind from the outside to multiple HLA-DR alleles.
      Such features of drug recognition may open new therapeutic possibilities to
      intervene with TCR-MHC interactions in a selective way.

PMID- 9620608
TI  - Characterization of murine CD70 by molecular cloning and mAb.
AB  - CD27, a member of the tumor necrosis factor (TNF) receptor family, has been
      implicated in T cell activation, T cell development and T-dependent antibody
      production by B cells. Its ligand CD70 has been identified only in humans, and,
      thus, physiological and pathological roles of the CD70-CD27 interaction remain to
      be determined in an experimental animal system. In the present study, we
      identified murine (m) CD70 by molecular cloning, and characterized its expression
      and function by generating an anti-mCD70 mAb. The mCD70 cDNA encoded a type II
      transmembrane glycoprotein of the TNF family, having 56.5% identity to the human
      CD70 amino acid sequence. The mCd70 gene was assigned in the central region of
      chromosome 17. To explore the expression and function of mCD70, we generated cDNA
      transfectants and anti-mCD70 mAb (FR70), which inhibited binding of a murine CD27
      Fc fusion protein (mCD27-Ig) to mCD70 transfectants. FR70, as well as mCD27-Ig,
      immunoprecipitated a 30-33 kDa surface protein from A20 and mCD70-P815 cells but
      not from P815 cells. The mCD70 transfectants exhibited a potent co-stimulatory
      activity for anti-CD3-stimulated T cell proliferation, which was blocked by FR70
      far more efficiently than mCD27-Ig. FR70 also abrogated the CD28-independent co
      stimulatory activity of A20 cells. The expression of mCD70 was detected on
      splenic T cells after stimulation with anti-CD3 and anti-CD28 mAb, and on splenic
      B cells after stimulation with anti-CD40 mAb. Cross-linking of surface Ig by anti
      IgM mAb did not induce the mCD70 expression but enhanced the anti-CD40-induced
      mCD70 expression on splenic B cells. These results suggest a contribution of CD70
      to murine T-B cognate interaction as proposed in the human system. FR70 will be
      useful for further investigating the physiological and pathological roles of the
      CD70-CD27 interaction in T cell development, T-dependent antibody production and
      various disease models in the murine system.

PMID- 9620609
TI  - Potential regulatory elements for germline transcription in or near murine
      Sgamma1.
AB  - We were interested in identifying cis-acting elements that regulate germline
      transcription and switch recombination of heavy chain genes. The murine gamma1
      heavy chain gene includes two DNase I hypersensitive sites, which may represent
      protein:DNA interactions important for germline transcription and switch
      recombination. One DNase hypersensitive site is at the promoter/I exon boundary
      (termed 'Site I'); we localized a second pair of DNase hypersensitive sites to
      just 5' of the Sgamma1 region (termed 'Site II'). The DNA region of
      hypersensitive Site II includes a NF-kappaB/Rel binding site and a STAT6 binding
      site. It is noteworthy that NF-kappaB and STAT6 are induced by the same agents
      (CD40 ligation and IL-4 respectively) that stimulate germline transcription and
      switch recombination of the murine gamma1 gene. Transgenes with the gamma1
      promoter region (DNase hypersensitive Site I), Igamma1 and DNase I hypersensitive
      Site II expressed germline transcripts with correct regulation, including IL-4
      inducibility. However, the level of stable transcripts produced by the transgenes
      was much lower than that of the endogenous gamma1 gene, a complete 17 kb gamma1
      transgene or a derivative of the 17 kb gamma1 transgene that lacked most of
      Cgamma1. The promoter/Igamma1/Site II transgenes lacked Sgamma1 and we found that
      gamma1 transgenes that lacked only Sgamma1 also expressed germline transcripts
      with proper regulation, but at a low level. This suggested that the Sgamma1
      region includes positive elements for regulation of the amount of germline
      transcripts.

PMID- 9620610
TI  - Human milk proteins including secretory IgA fail to elicit tolerance after
      feeding.
AB  - Oral administration of large doses of protein antigen generally induces a state
      of systemic unresponsiveness currently termed mucosally induced tolerance. In
      this study, we used human milk protein (HMP) without casein as a multi-protein
      antigen for the study of mucosally induced tolerance. The HMP utilized in this
      study mainly contained secretory (S) IgA, lactoferrin (Lf) and alpha-lactalbumin
      (Lact). When mice were given 1 or 25 mg of HMP orally 3 times or 25 mg orally
      four consecutive weeks prior to systemic immunization, antigen-specific serum IgG
      responses to HMP were induced by subsequent parenteral immunization with 100
      microg of HMP. Analysis of IgG subclasses revealed that IgG1 followed by IgG2b
      accounted for the IgG responses noted. When both HMP and ovalbumin (OVA) were fed
      to mice, tolerance developed to OVA but not to HMP. To further investigate the
      nature of immune responses seen following oral gavage of HMP, we examined
      responses to individual protein of HMP. Brisk serum IgG1 and IgG2b responses to
      both S-IgA and Lf were induced by oral followed by systemic immunization with
      HMP. Analysis of splenic CD4+ T cells from mice given oral HMP revealed
      production of Th2- but not Th1-type cytokines. These results show that oral
      administration of HMP preferentially induces exclusive Th2-type immune responses,
      which may prevent the development of HMP (S-IgA and Lf)-specific mucosally
      induced tolerance.

PMID- 9620611
TI  - Age-related propensity to peripheral expansion of Vgamma3+ gammadelta+ T
      lymphocytes after irradiation and bone marrow transplantation.
AB  - The age-related decline in T cell functions is generally considered to be due to
      changes in the responding alphabeta T cell populations as a result of impairment
      of T cell differentiation in the thymus. T cells bearing the gammadelta TCR are
      normally a minor subset of circulating T cells, but often the major T cell type
      among lymphocytes in epithelial tissues. In this paper we show that gammadelta T
      cells are expanded in lymph nodes of irradiated mice after syngenic bone marrow
      transplantation. Interestingly, these gammadelta T cells express mainly the
      Vgamma3 TCR, which is characteristic of dendritic epithelial T cells that can
      develop in athymic nude mice and may recognize self antigens. Since the
      peripheral expansion of Vgamma3 T lymphocytes is closely related to bone marrow
      age, these observations indicate that the age-related propensity to extrathymic
      development of Vgamma3+ gammadelta+ T lymphocytes is mainly due to stem cell
      dysregulation in aging. This phenomenon may contribute to T cell impairment and
      to the increased natural cytotoxic activity of lymphoid cells in aged mice.

PMID- 9620612
TI  - Inhibition of cruzipain visualized in a fluorescence quenched solid-phase
      inhibitor library assay. D-amino acid inhibitors for cruzipain, cathepsin B and
      cathepsin L.
AB  - A PEGA-resin was derivatized with a 3:1 mixture of hydroxymethyl benzoic acid and
      Fmoc-Lys(Boc)-OH and the fluorogenic substrate Ac-Y(NO2)KLRFSKQK(Abz)-PEGA was
      assembled on the lysine using the active ester approach. Following esterification
      of the hydroxymethyl benzoic acid with Fmoc-Val-OH a library XXX-k/r-XXXV
      containing approximately 200,000 beads was assembled by split synthesis. The
      resulting 'one bead, two peptides' library was subjected to extensive hydrolysis
      with cruzipain. One hundred darker beads were isolated and the 14 most
      persistently dark beads were collected and sequenced. The putative inhibitor
      peptides and several analogues were synthesized and found to be competitive
      microM to nM inhibitors of cruzipain in solution. The inhibitory activity was
      found to be unspecific to cruzipain when compared with cathepsins B and L and
      specific when compared with kallikrein. One of the inhibitors was docked into the
      active site of cathepsin B and was found most probably to bind to the enzyme
      cavity in an unusual manner, owing to the inserted D-amino acid residue.

PMID- 9620613
TI  - Bradykinin antagonists with dehydrophenylalanine analogues at position 5.
AB  - Continuing the studies on structural requirements of bradykinin antagonists, it
      has been found that analogues with dehydrophenylalanine (deltaPhe) or its ring
      substituted analogues (deltaPhe(X)) at position 5 act as antagonists on guinea
      pig pulmonary artery, and on guinea pig ileum. Because both organs are considered
      to be bradykinin B2 receptor tissues, the analogues with deltaPhe or deltaPhe(X)
      at position 5, but without any replacement at position 7, seem to represent a new
      structural type of B2 receptor antagonist. All the analogues investigated act as
      partial antagonists; they inhibit the bradykinin-induced contraction at low
      concentrations and act as agonists at higher concentrations. Ring substitutions
      by methyl groups or iodine reduce both the agonistic and antagonistic activity.
      Only substitution by fluorine gives a high potency. Incorporation of deltaPhe
      into different representative antagonists with key modifications at position 7
      does not enhance the antagonist activity of the basic structures, with one
      exception. Only the combination of deltaPhe at position 5 with DPhe at position 7
      increases the antagonistic potency on guinea pig ileum by about one order of
      magnitude. Radioligand binding studies indicate the importance of position 5 for
      the discrimination of B2 receptor subtypes. The binding affinity to the low
      affinity binding site (KL) was not significantly changed by replacement of Phe by
      deltaPhe. In contrast, ring-methylation of deltaPhe results in clearly reduced
      binding to KL. The affinity to the high-affinity binding site (KH) was almost
      unchanged by the replacement of Phe in position 5 by deltaPhe, whereas the
      analogue with 2-methyl-dehydrophenylalanine completely failed to detect the KH
      site. The peptides were synthesized on the Wang-resin according to the Fmoc/Bu(t)
      strategy using Mtr protection for the side chain of Arg. The dehydrophenylalanine
      analogues were prepared by a strategy involving PyBop couplings of the dipeptide
      unit Fmoc-Gly-deltaPhe(X)-OH to resin-bound fragments.

PMID- 9620614
TI  - Solution conformation of an immunogenic peptide from HRV2: comparison with the
      conformation found in a complex with a Fab fragment of an anti-HRV2 neutralizing
      antibody.
AB  - The conformation of a [15]-peptide (H-VKAETRLNPDLQPTE-NH2) from VP2 of rhinovirus
      HRV2 complexed with a Fab fragment was previously shown by X-ray crystallographic
      studies to be similar to the one found in the corresponding region of HRV1A.
      Antibodies raised against this peptide bind to and neutralize HRV2. In order to
      identify structural features preserved in solution that may explain the ability
      of this short peptide to mimic the structure of the protein surface, the peptide
      has been studied by NMR in aqueous solution as well as under denaturing
      conditions. The peptide is shown to be a random coil in solution. However, the
      sequence forming a 3(10)helix in the complex is biased into a helical
      conformation according to NOE intensity data as well as from urea and pH
      titrations. This sequence adopts the same conformation in an unrelated protein.
      NOE data suggest that a beta-turn found in the complex may be sampled in
      solution. Also, Glu4, interacting with Arg6 in the crystal, has a reduced pKa
      value in solution. It is concluded that the local structure present in the random
      coil state of VP2(156-170) contains enough information to direct the production
      of antibodies that bind to and neutralize HRV2.

PMID- 9620615
TI  - The maculatin peptides from the skin glands of the tree frog Litoria
      genimaculata: a comparison of the structures and antibacterial activities of
      maculatin 1.1 and caerin 1.1.
AB  - Six peptides have been isolated and characterized from the dorsal glands of the
      tree frog Litoria genimaculata. One of these is the known hypotensive peptide
      caerulein; the others have been named maculatins. The amino acid sequences of the
      maculatin peptides have been determined using a combination of fast atom
      bombardment mass spectrometry and automated Edman sequencing. Four of the
      maculatin peptides show antibiotic activity, with maculatin 1.1
      [GLFGVLAKVAAHVVPAIAEHF(NH2)] showing the most pronounced activity, particularly
      against gram-positive organisms. Maculatin 1.1 resembles the known caerin 1
      antibiotic peptides, except that four of the central amino acid residues (of the
      caerin 1 system) are missing in maculatin 1.1. A comparison of the antibiotic
      activity of maculatin 1.1 with those of caerin 1.1 is reported.

PMID- 9620616
TI  - Capping and dynamic relation between domains 1 and 2 of gelsolin.
AB  - Gelsolin is a protein that severs and caps actin filaments. The two activities
      are located in the N-terminal half of the gelsolin molecules. Severing and
      subsequent capping requires the binding of domains 2 and 3 (S2-3) to the side of
      the filaments to position the N-terminal domain 1 (S1) at the barbed end of actin
      (actin subdomains 1 and 3). The results provide a structural basis for the
      gelsolin capping mechanism. The effects of a synthetic peptide derived from the
      sequence of a binding site located in gelsolin S2 on actin properties have been
      studied. CD and IR spectra indicate that this peptide presented a secondary
      structure in solution which would be similar to that expected for the native full
      length gelsolin molecule. The binding of the synthetic peptide induces
      conformational changes in actin subdomain 1 and actin oligomerization. An
      increase in the polymerization rate was observed, which could be attributed to a
      nucleation kinetics effect. The combined effects of two gelsolin fragments, the
      synthetic peptide derived from an S2 sequence and the purified segment 1 (S1),
      were also investigated as a molecule model. The two fragments induced nucleation
      enhancement and inhibited actin depolymerization, two characteristic properties
      of capping. In conclusion, for the first time it is reported that the binding of
      a small synthetic fragment is sufficient to promote efficient capping by S1 at
      the barbed end of actin filaments.

PMID- 9620617
TI  - Preparation of fluorescence quenched libraries containing interchain disulphide
      bonds for studies of protein disulphide isomerases.
AB  - Protein disulphide isomerase is an enzyme that catalyses disulphide redox
      reactions in proteins. In this paper, fluorogenic and interchain disulphide bond
      containing peptide libraries and suitable substrates, useful in the study of
      protein disulphide isomerase, are described. In order to establish the chemistry
      required for the generation of a split-synthesis library, two substrates
      containing an interchain disulphide bond, a fluorescent probe and a quencher were
      synthesized. The library consists of a Cys residue flanked by randomized amino
      acid residues at both sides and the fluorescent Abz group at the amino terminal.
      All the 20 natural amino acids except Cys were employed. The library was linked
      to PEGA-beads via methionine so that the peptides could be selectively removed
      from the resin by cleavage with CNBr. A disulphide bridge was formed between the
      bead-linked library and a peptide containing the quenching chromophore (Tyr(NO2))
      and Cys(pNpys) activated for reaction with a second thiol. The formation and
      cleavage of the interchain disulphide bonds in the library were monitored under a
      fluorescence microscope. Substrates to investigate the properties of protein
      disulphide isomerase in solution were also synthesized.

PMID- 9620618
TI  - An efficient and convenient procedure for the synthesis of N(alpha)-Fmoc-O
      monobenzyl phosphonotyrosine.
AB  - An efficient procedure is described for the synthesis of N(alpha)-Fmoc-O
      monobenzyl phosphonotyrosine from the corresponding dibenzyl derivative by
      monodebenzylation in the presence of sodium iodide. A simple work up procedure
      removes the by-products and the monobenzylated phosphono product is obtained in
      high yield.

PMID- 9620619
TI  - Sensitivity of new radiopharmaceuticals.

PMID- 9620620
TI  - Synthesis and preliminary evaluation of 9-(4-[18F]-fluoro-3
      hydroxymethylbutyl)guanine ([18F]FHBG): a new potential imaging agent for viral
      infection and gene therapy using PET.
AB  - Synthesis and preliminary biological evaluation of 9-(4-[18F]-fluoro-3
      hydroxymethylbutyl)-guanine ([18F]FHBG) is reported. 9-(4-Hydroxy-3
      hydroxymethylbutyl)-guanine (penciclovir) 4 was converted to 9-[N2, O-bis
      (methoxytrityl)-3-(tosylmethybutyl)]guanine 7 by treatment with methoxytrityl
      chloride followed by tosylation. The tosylate 7 was reacted with either
      tetrabutylammonium fluoride or KF in the presence of kryptofix 2.2.2. to produce
      the 4-fluoro-N2-O-bis-(methoxytrityl) derivative 8. Removal of the methoxytrityl
      groups by acidic hydrolysis produced FHBG 5. Radiolabeled product [18F]FHBG was
      prepared by fluorination of the tosylate 7 with [18F]KF and kryptofix 2.2.2. The
      labeled product was isolated by HPLC purification on a reverse-phase C18 column,
      and eluted at 12 min with 15% acetonitrile in water at a flow rate of 2.25
      mL/min. Radiochemical yield was 8.0-22.3% with an average of 12% in 7 runs
      (corrected for decay). Synthesis time was 90 to 100 min including HPLC
      purification with radiochemical purity >99%, and average specific activity of 320
      mCi/micromol. In vitro studies of the compound in HT-29 colon cancer cells
      revealed 18.2-fold higher uptake into transduced cells compared to control in 3
      h. The agent may be useful for imaging viral infection or transfected cells in
      gene therapy.

PMID- 9620621
TI  - Synthesis and characterisation of [90Y]-Bz-DTPA-oct: a yttrium-90-labelled
      octreotide analogue for radiotherapy of somatostatin receptor-positive tumours.
AB  - An investigation into the in vitro behaviour of two yttrium-90-labelled
      somatostatin analogues was performed. Further in vivo characterisation was
      performed with the most promising agent. A new DTPA-octreotide analogue (Bz-DTPA
      oct) was synthesised by coupling a bifunctional DTPA chelator to the N-terminal
      amine of the D-Phe1 of Tyr3-octreotide. This new SRIF analogue and DTPA
      octreotide (OctreoScan) were radiolabelled with 90Y prior to serum stability
      being evaluated. Receptor binding assays were also performed on the two
      radioligands using rat cortex membranes. The [90Y]-Bz-DTPA-oct was further
      evaluated in vivo using tumour-bearing rats. The first conjugate (DTPA
      octreotide) bound with a high affinity to SRIF receptors and the 90Y complex was
      relatively stable in human serum (t1/2 3.8 d for 90Y lost to serum proteins). The
      second conjugate (Bz-DTPA-oct) also exhibited a high binding affinity to SRIF
      receptors, but it demonstrated an even slower loss of 90Y to serum proteins (t1/2
      12.1 d). The in vivo evaluation of the more stable [90Y]-Bz-DTPA-oct showed a
      very rapid and high accumulation in somatostatin receptor-positive tumours, which
      after 1 h resulted in tumour/nontumour ratios of 3.8, 21, and 4.9 (for blood,
      muscle, and liver, respectively). These tumour/nontumour ratios increased, and
      were by 24 h postinjection 138, 285, and 6.1 (for blood, muscle, and liver).
      Yttrium-90-labelled Bz-DTPa-oct is rapidly and selectively accumulated in
      somatostatin receptor-positive tissue. Octadentate Bz-DTPA-oct could be ligand
      for 90Y radiotherapy of somatostatin receptor-positive tumours and their
      metastases.

PMID- 9620622
TI  - Synthesis, in vitro binding, and tissue distribution of radioiodinated 2-[125I]N
      (N-benzylpiperidin-4-yl)-2-iodo benzamide, 2-[125I]BP: a potential sigma receptor
      marker for human prostate tumors.
AB  - The preclinical evaluation of a sigma receptor-specific radiopharmaceutical that
      binds to human prostate tumor cells with a high affinity is described. We have
      synthesized and radioiodinated 2-[125I]-N-(N-benzylpiperidin-4-yl)-2
      iodobenzamide (2-[125I]BP) that possesses high affinity for both sigma-1 and
      sigma-2 receptor subtypes that are expressed on a variety of tumor cells. 2-IBP
      was synthesized, purified and characterized by routine spectroscopic and
      analytical methods. Radioiodination was accomplished using an oxidative
      iododestannylation reaction in the presence of chloramine T in high yields (76%
      93%) with a very high-specific activity (1700-1900 Ci/mmol). The in vitro
      competition binding studies of 2-[125I]BP with various sigma receptor ligands in
      LnCAP human prostate tumor cells showed a dose-dependent saturable binding. The
      inhibition constants (Ki, nM) for binding of 2-[125I]BP to human prostate tumor
      cells for 4-IBP, haloperidol and 2-IBP were 4.09, 6.34 and 1.6 nM, respectively.
      The clearance of 2-[125I]BP, in Sprague-Dawley rats, was rapid from the blood
      pool, other normal tissues and the total body. Tissue distribution studies in
      nude mice bearing human prostate tumor (DU-145) also showed a fast clearance from
      normal organs. The tumor had the highest percentage of injected dose per gram
      (%ID/g) of all tissues at 4 h as well as 24 h (2.0 +/- 0.05 and 0.147 +/- 0.038
      ID/g, respectively) postinjection. The in vivo receptor binding specificity was
      demonstrated using haloperidol (a known high-affinity sigma receptor ligand). A
      significant decrease (> 50%, p = 0.001) was observed in tumor concentration when
      haloperidol was used as a blocking agent. The high affinity of 2-[125I]BP for
      sgma receptor-binding sites, its fast in vivo clearance from normal organs and
      its high uptake and retention in tumor implies that 2-[123I]BP or 2-[131I]BP may
      be a promising tracer for noninvasive imaging of human prostate tumors.

PMID- 9620623
TI  - Synthesis and preliminary evaluation of [11C]NE-100 labeled in two different
      positions as a PET sigma receptor ligand.
AB  - N,N-Dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]ethylamine (NE-100) was
      labeled with 11C in two different positions by the alkylation of an N-despropyl
      precursor with [11C]propyl iodide and of an O-desmethyl precursor with
      [11C]methyl iodide and was evaluated for the potential as a tracer for mapping
      sigma 1 receptors in the CNS and peripheral organs by PET. Following i.v.
      injection of [N-propyl-11C]NE-100 or [O-methyl-11C]NE-100 into mice, the two
      tracers showed similar tissue distribution patterns except for the liver and
      brain. With the coinjected carrier NE-100 or haloperidol, the uptake of [N-propyl
      11C]NE-100 by the liver, pancreas and spleen was significantly decreased at 15
      min after injection, whereas the effect was not significant for [O-methyl-11C]NE
      100. The coinjection of NE-100 enhanced the brain uptake of the two tracers.
      Haloperidol also enhanced the brain uptake of [N-propyl-11C]NE-100, but not that
      of [O-methyl-11C]NE-100. The regional brain distribution assessed with [O-methyl
      3H]NE-100 was consistent with the distribution pattern of the sigma receptors.
      Four sigma drugs reduced the regional brain uptake of [O-methyl-3H]NE-100 to 70%
      90% of the control. In an ex vivo autoradiographic study of the rat brain, the
      uptake of [O-methyl-11C]NE-100 was blocked by carrier NE-100 or haloperidol (53%
      59% of the control in the cortex), which suggests a receptor-specific
      distribution. These results show that [O-methyl-11C]NE-100 has limited potential
      as a PET ligand for mapping sigma 1 receptors in the peripheral organs and the
      CNS because of high nonspecific binding.

PMID- 9620624
TI  - Synthesis and evaluation of 11C-labeled nonpeptide antagonists for
      cholecystokinin receptors: [11C]L-365,260 and [11C]L-365,346.
AB  - 11C-labeled cholecystokinin (CCK) receptor antagonists, 3R(+)-N-(2,3-dihydro-1
      [11C]methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepine- 3-yl)-N'-(3-methylphenyl)urea
      ([11C]L-365,260) and its (S)-enantiomer ([11C]L-365,346), have been synthesized
      and evaluated in vivo for use in CCK receptor studies with positron emission
      tomography (PET). Selective N-methylation of a racemic precursor with
      [11C]iodomethane and subsequent optical resolution of the racemate with HPLC
      afforded optically pure [11C]L-365,260 and [11C]L-365,346, which are selective
      for CCK-B (central-type) receptors and CCK-A (peripheral-type) receptors,
      respectively. Biodistribution studies in mice showed very low brain uptakes
      (<0.8% dose/gram) of the radioactivities after intravenous injections of these
      compounds, although that of brain CCK-B receptor-selective [11C]L-365,260 was 2
      fold that of [11C]L-365,346. In peripheral organs, uptake of the radioactivity in
      the pancreas was the highest among the organs tested after the injection of
      [11C]L-365,346 and was 3-fold that of [11C]L-365,260. It was also observed that
      high uptake of [11C]L-365,346 in rat pancreas was significantly inhibited by a
      simultaneous injection with a large dose of L-365,346 (3 mg/kg). These
      preliminary results suggest that the nonpeptide CCK antagonist [11C]L-365,346 may
      be useful for probing pancreatic CCK-A receptors by PET. Owing to the very low
      brain permeability, however, [11C]L-365,260 may have no potential as a PET tracer
      for probing brain CCK-B receptors.

PMID- 9620625
TI  - Evaluation and metabolite studies of 125I- and 123I-labelled E-(R,R)-IQNP:
      potential radioligands for visualization of M1 muscarinic acetylcholine receptors
      in brain.
AB  - A new ligand for the M1 muscarinic receptor subtype, E-(R,R)-1
      azabicyclo[2.2.2]oct-3-yl alpha-hydroxy-alpha-(1-iodo-1-propen-3-yl)-alpha
      phenylacetate (E-IQNP), was labelled with 125I and 123I for autoradiographic
      studies on human whole-brain cryosections and SPET studies, respectively, in
      Cynomolgus monkey. Autoradiography demonstrated E-[125I]IQNP binding in M1
      receptor-rich regions such as the neocortex and the striatum. The binding was
      displaceable by the selective M1 antagonist biperiden. In vivo single photon
      emission tomography (SPET) studies with E-[123I]IQNP demonstrated a high
      accumulation of radioactivity in the monkey neocortex. Rapid hydrolysis of the
      quinuclidinyl ester to the free acid was found to be a major biotransformation
      route for E-[123I]IQNP. The free acid of E-[123I]IQNP does not pass the blood
      brain barrier, but the plasma concentration was high as compared to the total
      radioactivity in brain. It is thus necessary to correct for the high
      concentration of radioactive metabolites in parenchymal blood (CBV) to obtain
      accurate values for E-[123I]IQNP binding in brain.

PMID- 9620626
TI  - Characterisation of the appearance of radioactive metabolites in monkey and human
      plasma from the 5-HT1A receptor radioligand, [carbonyl-11C]WAY-100635-
      explanation of high signal contrast in PET and an aid to biomathematical
      modelling.
AB  - N-(2-(4-(2-Methoxy-phenyl)-1-piperazin-1-yl)ethyl)-N-(2-pyridyl)++
      +cyclohexanecarboxamide (WAY-100635), labelled in its amido carbonyl group with
      11C (t1/2 = 20.4 min), is a promising radioligand for the study of brain 5-HT1A
      receptors with positron emission tomography (PET). Thus, in PET experiments in
      six cynomolgus monkeys and seven healthy male volunteers, [carbonyl-11C]WAY
      100635 was taken up avidly by brain. Radioactivity was retained in regions rich
      in 5-HT1A receptors, such as occipital cortex, temporal cortex and raphe nuclei,
      but cleared rapidly from cerebellum, a region almost devoid of 5-HT1A receptors.
      [Carbonyl-11C]WAY-100635 provides about 3- and 10-fold higher signal contrast
      (receptor-specific to nonspecific binding) than [O-methyl-11C]WAY-100635 in
      receptor-rich areas of monkey and human brain, respectively. To elucidate the
      effect of label position on radioligand behaviour and to aid in the future
      biomathematical interpretation of the kinetics of regional cerebral radioactivity
      uptake in terms of receptor-binding parameters, HPLC was used to measure
      [carbonyl-11C]WAY-100635 and its radioactive metabolites in plasma at various
      times after intravenous injection. Radioactivity cleared rapidly from monkey and
      human plasma. Parent radioligand represented 19% of the radioactivity in monkey
      plasma at 47 min and 8% of the radioactivity in human plasma at 40 min. [Carbonyl
      11C]desmethyl-WAY-100635 was below detectable limits in monkey plasma and at most
      a very minor radioactive metabolite in human plasma. [11C]Cyclohexanecarboxylic
      acid was identified as a significant radioactive metabolite. In human plasma this
      maximally represented 21% of the radioactivity at 10 min after radioligand
      injection. All other major radioactive metabolites in monkey and human plasma
      were even more polar. No-carrier-added [carbonyl-11C]cyclohexanecarboxylic acid
      was prepared in the laboratory and after intravenous administration into
      cynomolgus monkey was shown with PET to give only a low uptake of radioactivity
      into brain tissue. The acid rapidly gave rise to several radioactive metabolites
      of higher polarity in plasma. The observed lack of any significant metabolism of
      [carbonyl-11C]WAY-100635 to highly lipophilic or pharmacologically potent
      radioactive compounds is consistent with its high signal contrast in primate
      brain.

PMID- 9620627
TI  - A novel areneisonitrile Tc complex inhibits the transport activity of MDR P
      glycoprotein.
AB  - P-glycoprotein (Pgp), the product of the multidrug resistance (MDR1) gene, has
      been an important cancer target for development of MDR modulators that act to
      inhibit Pgp efflux transport activity. From a series of novel substituted
      areneisonitrile analogues of Tc-sestamibi, a known Pgp transport substrate,
      emerged the hexakis(3,4,5-trimethoxyphenylisonitrile)Tc(I) complex (Tc-TMPI) as a
      potential modulator of Pgp. Tracer 99mTc-TMPI showed net cellular accumulation in
      inverse proportion to expression of Pgp and enhancement upon addition of classic
      MDR modulators. At pharmacological concentrations, the carrier-added 94Tc-TMPI
      complex showed potent inhibition of Pgp-mediated 99mTc-sestamibi transport (EC50,
      1.1 +/- 0.2 microM) and displacement of a Pgp-specific photolabel in a
      concentration-dependent manner. We conclude that 99Tc-TMPI directly inhibited Pgp
      transport activity and serves as a convenient template for development of
      nonradioactive Re(I) analogues as novel MDR modulators.

PMID- 9620628
TI  - 99mTc-MIBI, 99mTc-tetrofosmin and 99mTc-Q12 in vitro and in vivo.
AB  - The aim of this study was to compare uptake of 99mTc-MIBI, 99mTc-tetrofosmin and
      99mTc-Q12 in vitro and biodistribution in vivo in rats. In vitro, uptake
      decreased in the order MIBI-->tetrofosmin-->Q12. Uptake of MIBI and tetrofosmin,
      but not of Q12, in cultured tumor cells was dependent on the plasma membrane and
      mitochondrial potential. In vivo, heart uptake of all three compounds was high
      and stable. Tumor uptake decreased in the order MIBI-->Q12-->tetrofosmin and the
      tumor/blood ratio in the order MIBI-->tetrofosmin-->Q12.

PMID- 9620629
TI  - Vascular targeted radioimmunotherapy with 213Bi--an alpha-particle emitter.
AB  - To destroy both tumor blood vessels and adjacent tumor cells, an alpha-particle
      emitter, 213Bi, has been targeted with a monoclonal antibody (MAb) to vessels
      that feed lung tumors in mice. Animals, bearing approximately 100 EMT-6
      carcinomas each of 50-400 cells in size in the lung, that were treated with 120
      muCi of 213Bi-MAb 201B were all cured of their disease. Animals treated when
      tumors were larger (10(3)-10(4) cells) had extended life spans, but a small
      number of residual tumors eventually killed the animals. Significant extension of
      life span was also induced with another tumor model-rat tracheal carcinoma
      growing in the lungs of SCID mice that were then treated with 136 muCi 213Bi-MAb
      201B. These studies indicate that attack of both blood vessels and tumor cells
      simultaneously is an effective mode of cancer treatment.

PMID- 9620630
TI  - Glucose and methionine uptake by rat brain tumor treated with prodrug-activated
      gene therapy.
AB  - The effect of acyclovir (ACV) on the metabolism of rat 9L-gliosarcoma cells
      expressing the herpes simplex virus-thymidine kinase gene was studied using 2
      deoxy-2-[18F]fluoro-D-glucose (FDG) and L-[methyl-11C]methionine. Though the
      average weight of the tumors treated with ACV was significantly lower than that
      of the saline-injected control group, FDG and methionine uptake per weight of
      tumor tissue was not different between the two groups. This result exhibits a
      striking contrast to the metabolic pattern observed after radiation therapy,
      suggesting the different pathways regarding tumor cell death between the
      therapies.

PMID- 9620632
TI  - Elimination of free radionuclide by a chelating agent improves tumor-to-nontumor
      ratios following radioimmunotargeting with antibody labeled with 67Ga.
AB  - To circumvent radionuclide accumulation in nontarget tissues when employing
      metallic radionuclides for radioimmunoscintigraphy or radioimmunotherapy, we have
      investigated the effect of the chelating agent deferroxamine (DFO) on the
      biodistribution of 67Ga following its administration attached to intact
      monoclonal antibody MAb35 and its F(ab')2 fragment. Following administration of
      67Ga-labeled MAb35, DFO accelerated whole-body elimination of 67Ga and reduced
      its accumulation in several normal tissues, including liver, spleen and kidney.
      No reduction in tumor accumulation of 67Ga was observed. Following administration
      of 67Ga-labeled F(ab')2 fragment, kidney accumulation was higher than with the
      intact antibody (29% and 4% ID/g, respectively) and blood levels lower (0.69% and
      5% ID/g, respectively). Again, no alteration in tumor accumulation of 67Ga was
      seen following DFO, although liver, kidney and blood levels were reduced and
      whole-body elimination accelerated.

PMID- 9620631
TI  - Immunolymphoscintigraphy in breast cancer: evaluation using 131I-labeled
      monoclonal antibody B72.3.
AB  - Noninvasive axillary lymph node staging was investigated using [131I]murine
      monoclonal antibody B72.3 in 16 patients with breast cancer scheduled for
      axillary dissection. [131I]B72.3 was injected into ipsilateral finger webs or
      around the breast biopsy. Scintigraphy to 72 h and gamma
      counting/immunohistochemistry of nodes were performed. Specific antibody uptake
      (%ID/g) and the ratio of specific:nonspecific antibody uptake were not
      significantly different in tumor-positive versus tumor-negative nodes, suggesting
      that [131I]B72.3 is unsuitable to discriminate axillary node tumor involvement.

PMID- 9620633
TI  - Lysine-directed conjugation of ethidium homodimer to B72.3 antibody: retention of
      immunoreactivity but altered tumor targeting.
AB  - Ethidium homodimer (EHD) was conjugated to B72.3 monoclonal antibody using a
      method whereby 85-90% of the conjugated EHD remains available for DNA
      intercalation. Antibody was thiopropionylated by reaction with N-succinimidyl 3
      (2-pyridyldithio)propionate and reduction of pyridyldithio groups with
      dithiothreitol. EHD was maleimido-functionalized with succinimidyl-4-(N
      maleimidoethyl)cyclohexane-1-carboxylate and treated with thiopropionylated
      antibody to obtain a conjugate containing approximately 3.4 EHD per antibody
      molecule. For biologic studies, 14C-labeled EHD was synthesized by reductive
      amination and conjugated as above. In vitro the conjugate maintained chemical
      integrity and immunoreactivity, while in vivo its targeting of LS174T tumors was
      reduced compared with that of iodinated antibody. A decrease in isoelectric point
      of the immunoconjugate was also observed.

PMID- 9620634
TI  - In-vivo tissue uptake and retention of Sn-117m(4+)DTPA in a human subject with
      metastatic bone pain and in normal mice.
AB  - Organ and tissue uptake and retention of Sn-117m(4+)DTPA were studied in a human
      subject treated for metastatic bone pain, and the results were compared with the
      biodistribution studies in five normal mice. The explanted organs from a patient
      who received a therapy dose of 18.6 mCi (688.2 MBq) Sn-117m(4+)DTPA and who died
      47 days later were imaged with a gamma-camera, and tissue samples were counted
      and also autoradiographed. Bone, muscle, liver, fat, lungs, kidneys, spleen,
      heart and pancreas tissue samples were assayed in a well counter for
      radioactivity. Regions of interest were drawn over bone and major organs to
      calculate and quantify clearance times using three in vivo Sn-117m(4+)DTPA whole
      body scintigrams acquired at 1, 24 and 168 h after injection. Five normal mice
      injected with the same batch of Sn-117m(4+)DTPA as used for the human subject
      were sacrificed at 24 h, and tissue samples were collected and assayed for
      radioactivity for comparison with the human data. For the human subject, whole
      body retention at 47 days postinjection was 81% of the injected dose, and the
      rest (19%) was excreted in urine. Of the whole-body retained activity at 47 days,
      82.4% was in bone, 7.8% in the muscle and 1.5% in the liver, and the rest was
      distributed among other tissues. Gamma-ray scintigrams and electron
      autoradiographs of coronal slices of the thoracolumbar vertebral body showed
      heterogeneous metastatic involvement with normal bone between metastatic lesions.
      There was nonuniform distribution of radioactivity even within a single vertebral
      body, indicating normal bone between metastatic lesions. Lesion-to-nonlesion
      ratios ranged from 3 to 5. However, the osteoid-to-marrow cavity deposition
      ratio, from the microautoradiographs, was 11:1. The peak uptake in the human bone
      was seen at 137 h with no biological clearance. Soft tissues showed peak uptake
      at 1 h and exhibited three compartmental clearance components. Whole-body
      retention in normal mice was 38.7% of the injected dose at 24 h and the rest was
      excreted. At 24 h postinjection, bone in mice showed 84.2% of the whole-body
      retention, muscle 1.7% and liver 1.4%, and the rest was distributed in other soft
      tissues. Percent distribution of the retained dose among bone, muscle, liver and
      other soft tissues is very similar between mice and a human subject. To calculate
      precise radiation absorbed doses from bone pain palliation radionuclides, it is
      necessary to take into account soft-tissue uptake and retention that may not be
      readily evident from routine external gamma-scintigraphy.

PMID- 9620635
TI  - First-pass cerebral extraction of benzamide-derivative radiotracers for SPECT.
AB  - Central dopaminergic receptors are widely studied for their importance in the
      pathophysiology of neurological and psychiatric diseases. We have investigated
      the cerebral delivery kinetics of three dopaminergic ligands in rats through the
      use of an indicator fractionation method to measure the tracer's regional influx
      rate constant with respect to regional blood flow. The aim is to collect the in
      vivo kinetic parameters of the radioligand cerebral distribution, which are
      necessary if, dealing with SPECT and "trapped" tracers, one wishes to analyse
      data using a graphical approach.

PMID- 9620636
TI  - Synthesis and evaluation of hydroxamamide-based tetradentate ligands as a new
      class of thiol-free chelating molecules for 99mTc radiopharmaceuticals.
AB  - Both N,N'-ethylene bis(benzohydroxamamide) [(C2(BHam)2)] and N,N'-propylene
      bis(benzohydroxamamide) [(C3(BHam)2)] were designed as new thiol-free chelating
      molecules for 99mTc radiopharmaceuticals. Synthetic procedures using oxadiazoline
      intermediates were developed for C2(BHam)2 and C3(BHam)2. Both C2(BHam)2 and
      C3(BHam)2 formed 99mTc complexes with high yields over a wide pH range (pH 3-12)
      at room temperature. Complexation yields of over 95% were achieved at ligand
      concentrations as low as 2.5 x 10(-6) M. Reversed-phase HPLC analyses indicated
      that both C2(BHam)2 and C3(BHam)2 formed 99mTc complexes as single species with
      stabilities much higher than those of 99mTc-BHam. Selective complex formation of
      99mTc with the two ligands was observed in the presence of human IgG. No
      decomposition with low protein binding were demonstrated when the two 99mTc
      complexes were incubated in murine plasma. Although further structural studies
      are required, these findings implied that the Ham-based tetradentate ligands
      would serve as new chelating molecules for 99mTc radiopharmaceuticals.

PMID- 9620637
TI  - Radiochemical and radiopharmacological properties of pirocarbotrat and other
      labeled charcoal dispersions: comparative studies in rats with NMU-induced
      mammary tumors.
AB  - The purpose of this work is to study the physicochemical properties of
      Pirocarbotrat to explain its radiopharmacological behavior. We also studied a
      mixture of charcoal plus chromic [32P]phosphate and charcoal plus sodium
      [32P]orthophosphate only for comparative purposes. The results show that the mean
      diameter of the Pirocarbotrat particles was 2.5 microm with an homogeneous
      distribution, while the other products show an heterogeneous distribution of the
      particle sizes, with a mean size diameter between 0.5 and 0.9 microm. Hydrolysis
      studies with a solution of 0.1 N HCl and with sulfochromic mixture revealed that
      in Pirocarbotrat the 32P is strongly bound to the charcoal particles.
      Bioelimination studies of Pirocarbotrat show that the total eliminated activity
      was 12.70 +/- 3.90%, with a higher amount in urine (8.30 +/- 1.80%) than in feces
      (4.40 +/- 3.50%). When biodistribution studies of Pirocarbotrat were carried out,
      we found that the 84.50 +/- 2.60% of the activity remained in the tumor with
      almost null irradiation of the other organs under study. When therapeutic action
      was evaluated, we observed that the percentage of tumor regression was 78.3% for
      the tumors injected with Pirocarbotrat. The other dispersions under study showed
      different behaviors with high activity percentages distributed throughout the
      organism. These studies demonstrate that Pirocarbotrat has the best
      radiopharmacological properties to ensure irradiation of the tumor with the least
      concomitant irradiation of surroundings or other organs or tissues.

PMID- 9620638
TI  - Formulation of 99mTc-Sn-EDTMP: freeze-dried kit for bone scanning.

PMID- 9620639
TI  - Forty years of interferon, forty years of cytokines.

PMID- 9620640
TI  - Signaling mechanisms through gp130: a model of the cytokine system.
AB  - The interleukin-6 cytokine family plays roles in a wide variety of tissues and
      organs, including the immune hematopoietic and nervous systems. Gp130 is a signal
      transducing subunit shared by the receptors for the IL-6 family of cytokines. The
      binding of a ligand to its receptor induces the dimerization of gp130, leading to
      the activation of JAK tyrosine kinase and tyrosine phosphorylation of gp130.
      These events lead to the activation of multiple signal-transduction pathways,
      such as the STAT, Ras-MAPK and PI-3 kinase pathways whose activation is
      controlled by distinct regions of gp130. We propose a model showing that the
      outcome of the signal transduction depends on the balance or interplay among the
      contradictory signal transduction pathways that are simultaneously generated
      through a cytokine receptor in a given target cell.

PMID- 9620641
TI  - Interleukin-1.
AB  - Interleukin-1 (IL-1) is the prototypic pro-inflammatory cytokine. There are two
      forms of IL-1, IL-1alpha and IL-1beta and in most studies, their biological
      activities are indistinguishable. IL-1 affects nearly every cell type, often in
      concert with another pro-inflammatory cytokine, tumor necrosis factor (TNF).
      Although IL-1 can upregulate host defenses and function as an immunoadjuvant, IL
      1 is a highly inflammatory cytokine. The margin between clinical benefit and
      unacceptable toxicity in humans is exceedingly narrow. In contrast, agents that
      reduce the production and/or activity of IL-1 are likely to have an impact on
      clinical medicine. The synthesis, processing, secretion and activity of IL-1,
      particularly IL-1beta, are tightly regulated events. A unique aspect of cytokine
      biology is the naturally occurring IL-1 receptor antagonist (IL-1Ra). IL-1Ra is
      structurally similar to IL-1beta but lacking agonist activity is used in clinical
      trials to reduce disease severity. In addition, regulation of IL-1 activity
      extends to low numbers of surface receptors, circulating soluble receptors and a
      cell surface "decoy" receptor to down-regulate responses to IL-1beta. This review
      updates the current knowledge on IL-1.

PMID- 9620642
TI  - TGF-beta in the central nervous system: potential roles in ischemic injury and
      neurodegenerative diseases.
AB  - The Transforming Growth Factor-betas (TGF-beta) are a group of multifunctional
      proteins whose cellular sites of production and action are widely distributed
      throughout the body, including the central nervous system (CNS). Within the CNS,
      various isoforms of TGF-beta are produced by both glial and neural cells. When
      evaluated in either cell culture or in vivo models, the various isoforms of TGF
      beta have been shown to have potent effects on the proliferation, function, or
      survival of both neurons and all three glial cell types, astrocytes, microglia
      and oligodendrocytes. TGF-beta has also been shown to play a role in several
      forms of acute CNS pathology including ischemia, excitotoxicity and several forms
      of neurodegenerative diseases including multiple sclerosis, Parkinson's disease,
      AIDS dementia and Alzheimer's disease.

PMID- 9620643
TI  - The growing family of interferon regulatory factors.
AB  - Interferons (IFN) exert their multiple biological effects through the induction
      of expression of over 30 genes encoding proteins with antiviral,
      antiproliferative and immunomodulatory functions. Among the many IFN-inducible
      proteins are the Interferon Regulatory Factors (IRFs), a family of transcription
      regulators, originally consisting of the well-characterized IRF-1 and IRF-2
      proteins; the family has now expanded to over 10 members and is still growing.
      The present review provides a detailed description of recently characterized IRF
      family members. Studies analyzing IRF-expressing cell lines and IRF knockout mice
      reveal that each member of the IRF family exerts distinct roles in biological
      processes such as pathogen response, cytokine signalling, cell growth regulation
      and hematopoietic development. Understanding the molecular mechanisms by which
      the IRFs affect these important cellular events and IFN expression will
      contribute to a greater understanding of events leading to various viral, immune
      and malignant disease states and will suggest novel strategies for antiviral and
      immune modulatory therapy.

PMID- 9620644
TI  - Signaling from the IL-2 receptor to the nucleus.
AB  - Interleukin-2 has pleiotropic actions on the immune system and plays a vital role
      in the modulation of immune responses. Our current understanding of IL-2
      signaling has resulted from in vitro studies that have identified the signaling
      pathways activated by IL-2, including the Jak-STAT pathways, and from in vivo
      studies that have analyzed mice in which IL-2, each chain of the receptor, as
      well a number of signaling molecules have been individually targeted by
      homologous recombination. Moreover, mutations in IL-2Ralpha, gamma(c) and Jak3
      have been found in patients with severe combined immunodeficiency. In addition,
      with the discovery that two components of the receptor, IL-2Rbeta and gamma(c),
      are shared by other cytokine receptors, we have an enhanced appreciation of the
      contributions of these molecules towards cytokine specificity, pleiotropy and
      redundancy.

PMID- 9620645
TI  - Clinical assessment of asymptomatic knees: comparison of men and women.
AB  - Two hundred ten adults, 100 women and 110 men, were recruited on the condition of
      always having asymptomatic knee joints. These recruits were initially solicited
      by newspaper advertisement. The women were recruited in 3 weeks, but additional
      efforts and 3 months were necessary to assemble the group of men. The volunteers
      underwent a uniform comprehensive medical history questionnaire, physical
      examination, and plain film radiographs. The data collected were subjected to
      computerization and statistical analysis. Although these subjects were always
      asymptomatic, only 4.5% of 200 women's knees and 21% of 220 men's knees had no
      "positive" physical findings. The findings of hypermobile patella, patellar
      crepitus, and lateral patellar position on Merchant x-ray view were common.
      Findings not present or infrequent in these asymptomatic subjects and potentially
      pathological were patellar J-sign, decreased range of motion, asymmetrical
      ligamentous laxity, McMurray's sign, compartmental crepitus, and severe
      degenerative arthritis or loose bodies on radiograph. The findings in women were
      different from those observed in men. This gender-specific information should be
      helpful in patient management but also useful and timely for establishing
      practice guidelines, treatment algorithms, and outcome study instruments.

PMID- 9620646
TI  - Arthroscopic meniscal repair with fibrin clot of complete radial tears of the
      lateral meniscus in the avascular zone.
AB  - Peripheral lateral meniscal tears are amenable to arthroscopic meniscal repair.
      However, the posterolateral aspect of the lateral meniscus adjacent to the
      popliteus tendon is devoid of penetrating peripheral vessels and therefore
      difficult to heal. A complete radial split at this site is usually treated with
      total meniscectomy. We report five cases of a tear of the posterolateral aspect
      of the lateral meniscus anterior to the popliteus fossa. All patients had a
      radial split that extended to the popliteus tendon. In all cases, the repair was
      enhanced with a fibrin clot. Second-look arthroscopy showed that healing of the
      periphery occurred in all of the cases. All patients returned to their initial
      level of sports activity. Three of five patients were available for follow-up at
      an average of 71 months, and magnetic resonance imaging was performed at that
      time to assess the previously repaired meniscus. All menisci were fully healed
      and showed no further signs of degeneration. The ability of an exogenous fibrin
      clot to stimulate and support a reparative response in the avascular portion of
      the meniscus may represent a potential method of repair. Awareness of the
      relatively low healing potential of this zone and enhancement of healing
      opportunities should improve outcome.

PMID- 9620647
TI  - The effect of aging and osteoarthritis on the mature and senescent cross-links of
      collagen in human meniscus.
AB  - Pyridinoline and deoxypyridinoline are mature cross-links maintaining the
      structure of collagen, whereas pentosidine is a senescent cross-link that
      increases with age. The aim of this study was to investigate the effect of aging
      and osteoarthritis on these cross-links in human meniscus. Meniscus was obtained
      from 21 patients with osteoarthritis and 26 nonarthritic trauma patients.
      Hydroxyproline was measured in hydrolyzed samples. The amount of pyridinoline,
      deoxypyridinoline, and pentosidine cross-links measured in the hydrolyzed samples
      using a fluorescent high-performance liquid chromatography technique was
      expressed per hydroxyproline. There was no correlation between hydroxyproline,
      pyridinoline, or deoxypyridinoline and age, but pentosidine exponentially
      increased with age. There was no difference in hydroxyproline nor cross-links
      between the peripheral and central portions of the meniscus. There was no
      significant difference in hydroxyproline between osteoarthritis and nonarthritis.
      Pyridinoline and deoxypyridinoline in osteoarthritis were significantly lower
      than in nonarthritis. Pentosidine in osteoarthritis was somewhat higher than that
      in nonarthritis, but not significantly so. The increase of pentosidine with aging
      may relate to age-related degeneration of meniscus. In osteoarthritis, the
      decrease of pyridinoline and deoxypyridinoline may cause and progress the
      degeneration of meniscus attributable to osteoarthritis.

PMID- 9620648
TI  - Subtalar arthroscopy: indications, technique, and results.
AB  - The purpose of this study was to present the indications, technique, and results
      for subtalar arthroscopy in 50 consecutive patients. In each case, ankle
      arthroscopy was performed concomitantly to assess the exact source of the
      patient's pain. Surgical indications included chronic pain, swelling, buckling,
      and/or locking that failed conservative treatment. Arthroscopy of the ankle and
      subtalar joints were performed using both 2.7- and 1.9-mm arthroscopes through
      standard and accessory portals; distraction was used in all cases. All patients
      were followed-up for an average of 48 months (range, 36 to 70 months). Group 1
      included 21 patients (42%) with chronic lateral ankle pain following an inversion
      injury. In this group, the subtalar joints were completely normal and the
      pathology was found to be limited only to the ankle joint. In group 2, 29
      patients (58%) had the following diagnoses at arthroscopy: synovitis, 7;
      degenerative joint disease, 5; subtalar dysfunction, 5; chondromalacia, 4;
      nonunion of os trigonum, 4; arthrofibrosis, 2; loose bodies, 1; and osteochondral
      lesions of the talus, 1. Overall, the results were 86% good-to-excellent in group
      2.

PMID- 9620649
TI  - Arthroscopic acromioplasty: a 6- to 10-year follow-up.
AB  - Arthroscopic acromioplasty has become a common procedure for the treatment of
      chronic impingement syndrome. Short-term studies have consistently shown good
      results; however, long-term data have not previously been reported in the
      literature. Of 102 consecutive patients undergoing arthroscopic acromioplasty at
      our institution from 1984 to 1988, 82 patients (83 shoulders) were available for
      evaluation. The patients were reviewed after a mean of 8 years, 5 months from
      their original surgery. There were 16 failures (19%) with unsatisfactory results
      following surgery; 13 patients (15%) required further surgery to relieve
      persistent pain. Thirty-three percent of all patients previously involved in
      sports were unable to return to overhead and throwing sports due to pain and lack
      of power with throwing. Overall, 81% of patients in our series had good to
      excellent results after 6 to 10 years. To optimize the indications for the
      procedure, other causes of impingement, such as occult instability and
      degenerative joint disease, should be ruled out. Throwers may have difficulty
      returning to their sport at the same level of intensity, and should be addressed
      independently.

PMID- 9620650
TI  - Intraoperative decision making in the treatment of shoulder instability.
AB  - Between April 1990 and April 1994, 100 patients with a preoperative diagnosis of
      anterior instability underwent a diagnostic arthroscopy of the shoulder. Patients
      with isolated SLAP lesions were excluded from the study. Patients with
      multidirectional instability, bony Bankart lesions, and large Hill-Sachs lesions
      were also excluded. Football players and dominant arm throwing athletes were also
      excluded. Thirty patients remained who had post-traumatic, unidirectional,
      anterior instability and a repairable Bankart lesion and did not have any
      exclusions as noted above. All of these patients underwent an initial attempt at
      an arthroscopic Sure-Tac stabilization (Smith & Nephew, Andover, MA). Twenty
      three patients met our criteria for a secure fixation but 7 did not. These 7
      underwent an immediate arthrotomy and open Bankart repair. All of the patients
      were available at follow-up at an average of 47 months (range, 36 to 72 months).
      The patients were evaluated by the Rowe shoulder rating scale. There have been
      two cases of recurrent subluxation and one case of recurrent dislocation in the
      Sure-Tac group. All three occurred over 2 years later. All three had recurrent
      Bankart lesions and underwent an arthrotomy and Bankart repair. There were no
      cases of recurrence of subluxation or dislocation in our initial open Bankart
      repair group. Sure-Tac arthroscopic anterior stabilization of the shoulder can
      initially give good results but these results appear to deteriorate over time and
      increased activity of the patient. We currently do not recommend a Sure-Tac
      repair even in a selective group of patients with an isolated Bankart lesion.
      This is based on our excellent results following an open Bankart repair and a 13%
      recurrence rate following Sure-Tac stabilization in carefully selected patients.

PMID- 9620651
TI  - The effect of radiofrequency energy on the length and temperature properties of
      the glenohumeral joint capsule.
AB  - The purpose of this in vitro study was to evaluate the effect of radiofrequency
      energy on the length and temperature properties of the glenohumeral joint capsule
      in a sheep model. Dissected glenohumeral joint capsules were placed in a 37
      degrees C tissue bath and treated with radiofrequency energy at temperature
      settings of 60 degrees, 65 degrees, 70 degrees, 75 degrees and 80 degrees C.
      Pretreatment and posttreatment tissue length was measured, and tissue temperature
      changes were recorded at distances of 0.0, 0.5, 1.0, 1.5 mm away from the probe
      path. Tissue shrinkage was found to be less than 4% for treatments below 65
      degrees C, and increased to 14% for treatments at 80 degrees C. Posttreatment
      lengths of tissues treated at 65 degrees, 70 degrees, 75 degrees, 80 degrees C
      were significantly shorter than pretreatment lengths. The maximum tissue
      temperatures directly below the probe were observed to be 3.7 degrees to 6.7
      degrees C lower than the set temperatures. As the distance from the probe was
      increased, the tissue temperature was found to decrease, reaching a value of less
      than 45 degrees C at 1.5 mm for all five treatment temperature settings. This
      study provided basic information on temperature settings, tissue shrinkage, and
      tissue temperature distribution of radiofrequency treatment.

PMID- 9620652
TI  - Massive intraperitoneal and extraperitoneal accumulation of irrigation fluid as a
      complication during knee arthroscopy.
AB  - A case of uncommon fluid extravasation during knee arthroscopy leading to a
      swelling of the groin, scrotum, and penis, with massive intraperitoneal and
      retroperitoneal fluid accumulation is reported. A defective pump pressure sensor
      relay was found to be the cause of uncontrolled fluid delivery with excessive
      intra-articular pressure increase. The literature reports several cases of
      extravasation of irrigation fluid into the calf without any sequelae. Our patient
      experienced proximal expansion of the fluid that expanded along the vastus
      intermedius and shunted into the retroperitoneal and intraperitoneal space. There
      was no clinical evidence of compartment syndrome despite the excessive amount of
      extravasation in the thigh. Diuretics were administrated, and the fluid was
      excreted within 36 hours. The patient suffered of no further sequelae.

PMID- 9620653
TI  - Arthroscopic removal of an osteoid osteoma at the talar neck.
AB  - The case of a 14-year-old girl with osteoid osteoma of the talar neck that
      localized subperiostaly with a 1-year history of persistent ankle pain is
      presented. The diagnosis was made on the basis of clinical appearance,
      radiography, technetium-99m diphosphonate scintigraphy, and magnetic resonance
      imaging findings. Subsequently, she underwent arthroscopic excision of the lesion
      using a motorized burr and curette. After the intervention, there was prompt
      relief of symptoms and no recurrence during a follow-up period of 22 months.
      However, pathological study of the arthroscopic shavings failed to confirm the
      preoperative diagnosis. We concluded that the arthroscopic excision of an osteoid
      osteoma in an accessible location on the talar neck is an appropriate surgical
      intervention, but it should be done by using nonmotorized instruments for better
      pathological examination of the lesion.

PMID- 9620654
TI  - Monoclonal antibodies to the common gamma-chain as cytokine receptor antagonists
      in vivo: effect on intrathymic and intestinal intraepithelial T lymphocyte
      development.
AB  - Mice lacking a functional gamma c subunit of cytokine receptors exhibit profound
      defects in the development of multiple lymphoid lineages. To investigate the role
      of gamma c-dependent cytokines in T cell development, the phenotype of developing
      T cells was compared in interleukin (IL)-7Ralpha-deficient mice and anti-gamma c
      mAb-treated chimeric mice reconstituted with adult bone marrow cells or subsets
      of pro-T cells. These studies indicate that gamma c contributes to T cell
      development at multiple stages of pro-T cell maturation and that IL-7/IL-7R is
      the primary cytokine for thymic-dependent T cell development. However, our data
      also implicate other gamma c-dependent cytokines during thymic T cell
      development. By contrast, substantial intestinal intraepithelial lymphocytes
      (IEL) development was observed in the intestinal intraepithelium in both types of
      mice. Analysis of IL-7Ralpha-deficient mice indicates that the IL-7/IL-7R system
      is critical only for the development of TCR gammadelta+ IEL. However, the
      inhibitory activity of the anti-deltac mAb in the chimeric mouse model suggests
      that additional gamma cutilizing cytokines regulate the development of the
      remaining subsets of IEL.

PMID- 9620655
TI  - Signal transduction pathways activated by the IL-1 receptor family: ancient
      signaling machinery in mammals, insects, and plants.
AB  - Interleukin-1 (IL-1) is a central regulator of the immune and inflammatory
      responses. Recently, significant advances have been made in the area of IL-1
      receptors and IL-1 signal transduction. A family of proteins has been described
      that share significant homology in their signaling domains with the Type I IL-1
      receptor (IL-1RI). These include the IL-1 receptor accessory protein (IL-1AcP),
      which does not bind IL-1 but is essential for IL-1 signaling; a Drosophila
      protein Toll; a number of human Toll-like receptors (hTLRs); the putative IL
      18/IL-1-gamma receptor IL-1Rrp (IL-1 receptor-related protein); and a number of
      plant proteins. All appear to be involved in host responses to injury and
      infection. These homologies also extend to novel signaling proteins implicated in
      IL-1 action. Two IL-1 receptor-associated kinases, IRAK-1 and IRAK-2, which have
      homologs in Drosophila (Pelle) and plants (Pto), have been implicated in the
      activation of the transcription factor, nuclear factor kappaB (NF-kappaB). IRAK-1
      has also been implicated in AP1 induction, Jun amino-terminal kinase (JNK)
      activation, and IL-2 induction. It recruits the adapter protein TRAF6 to the IL-1
      receptor complex via an interaction with IL-1AcP. TRAF6 then relays the signal
      via NF-kappaB-inducing kinase (NIK) to two I-kappaB kinases (IKK-1 and -2),
      leading to NF-kappaB activation. Progress has also been made on other IL-1
      responsive kinases, including JNK and p38 MAP kinase, with the latter having a
      role in multiple responses to IL-1. The remarkable conservation between diverse
      species indicates that the IL-1 system represents an ancient signaling machine
      critical for responses to environmental stresses and attack by pathogens.

PMID- 9620656
TI  - Overview of interleukin-18: more than an interferon-gamma inducing factor.
AB  - Initially described in 1989 as interferon-gamma (IFN-gamma) inducing factor
      (IGIF), interleukin-18 (IL-18) is a novel pro-inflammatory cytokine that is
      clearly more than an inducer of IFN-gamma. The cytokine possesses several
      biological properties such as activation of nuclear factor-kappaB (NF-kappaB),
      Fas ligand expression, the induction of both CC and CXC chemokines, and increased
      production of competent human immunodeficiency virus. Most activities are due to
      a receptor complex that recruits the IL-1 receptor-activating kinase (IRAK),
      leading to translocation of NF-kappaB. This property and others support the
      concept that IL-18 is related to the IL-1 family. Indeed, one of the IL-18
      receptor chains is the IL-1 receptor-related protein, a member of the IL-1R
      family. In addition, IL-18 is structurally similar to IL-1beta and like IL-1beta
      is first synthesized as a leaderless precursor requiring the IL-1beta converting
      enzyme for cleavage into an active molecule. The biology of IL-18 is reviewed in
      the overview and the implication for a role for this cytokine in disease is
      presented.

PMID- 9620657
TI  - The SOCS proteins: a new family of negative regulators of signal transduction.
AB  - The negative regulation of cytokine signaling, with the exception of the tyrosine
      phosphatases, is not widely understood. We recently identified a new family of
      negative regulators by retroviral expression of hematopoietic cDNA library in the
      monocytic leukemic cell line, M1. This was coupled with selection for cells that
      were no longer able to differentiate in response to interleukin-6. From this
      screen, SOCS-1 was cloned and was shown to arrest cytokine signaling by binding
      to and inhibiting the intrinsic enzymatic activity of the JAK family of protein
      tyrosine kinases. SOCS-1 expression is induced in response to a range of
      cytokines and as such is thought to form part of a classic negative feedback
      loop. The SOCS family of proteins is linked by the presence of a conserved
      carboxy-terminal domain termed the SOCS box and now encompasses five distinct
      protein groups on the basis of the structural elements found amino-terminal to
      the SOCS box: (1) those that contain SH2 domains, (2) those that contain WD-40
      repeats, (3) ankyrin repeats, (4) SPRY domains, and (5) GTPase domains. As yet
      the function of the SOCS box remains unknown, but given the level of conservation
      within such diverse proteins, it is likely to have a broadly similar role in
      each.

PMID- 9620658
TI  - T cell development and activation in Jak3-deficient mice.
AB  - Jak3, a member of the Janus family of tyrosine kinases, participates in signaling
      through cytokine receptors that contain the common gamma-chain, including the
      receptors for interleukin (IL)-2, IL-4, IL-7, IL-9, and IL-15. Jak3- and gamma c
      deficient mice have pleiotropic defects that can be attributed to their inability
      to respond to multiple specific cytokines. A great deal of recent work has
      focused on the T cell defects in these mutant mice. Specifically, Jak3- and gamma
      c-deficient mice have small thymuses revealing a defect in T cell development,
      and in addition, have functionally unresponsive peripheral T cells with an
      activated/memory cell phenotype. The thymic defect in these mutant mice strongly
      resembles that seen in IL-7 and IL-7 receptor knockout mice, suggesting that the
      lack of IL-7 receptor signaling accounts for this defect in Jak3-/- and gamma c-
      mice. To characterize this defect further, we have examined the earliest stages
      of T cell development in adult and fetal Jak3-/- thymuses. These studies identify
      two discrete developmental defects at the CD4-CD8- stage of T cell maturation.
      Analyses of peripheral T cells in Jak3-/- and gamma c- mice have also revealed a
      number of abnormalities. All of the T cells in these mutant mice have an
      activated phenotype and a large fraction of them are proliferating in vivo. In
      addition, Jak3-/- and gamma c- T cells are more prone to undergo apoptosis than
      wild-type T cells. Together, these features account for the decreased IL-2
      secretion by in vitro-stimulated Jak3-/- T cells. Overall, many of the lymphoid
      defects of Jak3- and gamma c-deficient mice can be accounted for by the lack of
      IL-7R and IL-2R signaling; however, other cytokine systems must also be involved
      in maintaining peripheral T cell homeostasis.

PMID- 9620659
TI  - Distinct adapter proteins mediate acid versus neutral sphingomyelinase activation
      through the p55 receptor for tumor necrosis factor.
AB  - Ceramide, generated by the enzymatic function of sphingomyelinases (SMases) has
      emerged as an important signaling pathway transducing diverse biological effects
      of various cytokine receptors. The 55-kDa receptor for tumor necrosis factor (TNF
      R55) activates two types of SMases through distinct cytoplasmic domains. The
      death domain that is responsible for the initiation of the apoptotic pathway also
      signals for the activation of an acid SMase (A-SMase). The adapter protein TRADD
      binds to TNF-R55 in a ligand-dependent manner and serves as anchor for the
      subsequent recruitment of other proteins into the signaling complex that directly
      lead to cell death or nuclear factor-kappaB (NF-kappaB) induction. Notably, the
      two pro-apoptotic adapter proteins TRADD and FADD are also involved in the
      activation of A-SMase. In contrast, the NF-kappaB-inducing adapters TRAF2 and RIP
      do not signal for A-SMase. Thus, activation of A-SMase appears to belong to
      signals leading to TNF-induced cell death. A second signaling domain (NSD) is
      located upstream of the death domain and directly links the TNF-R55 to the
      activation of a neutral SMase (N-SMase). A novel adapter protein, FAN, has been
      identified that specifically binds to the NSD. FAN contains five WD repeats at
      its carboxy terminus, while it shows significant sequence homology with the mouse
      beige protein and its human homolog, the CHS protein, in the center portion of
      the protein. Overexpression of full-length FAN enhanced N-SMase activity in TNF
      treated cells, whereas truncated mutants of FAN produced dominant negative
      effects. FAN, however, did not interfere with any of the TNF responses signaled
      for by the death domain. Taken together, our data suggest that distinct
      cytoplasmic domains of TNF-R55 initiate independent signaling pathways by binding
      different adapter proteins.

PMID- 9620660
TI  - Leukocytes of the intestinal muscularis: their phenotype and isolation.
AB  - The basal presence of immunologically potent cells within the intestinal
      muscularis externa and their functional significance is unclear. Our aim was to
      investigate the basal distribution of various leukocyte populations within the
      rat jejunal muscularis. In addition, we sought to immunohistochemically phenotype
      the muscularis macrophage in jejunal whole-mounts, isolate these cells in primary
      culture, and investigate their ontogenesis. Macrophages form a regularly
      distributed network that expresses major histocompatibility complex class II,
      CD14 receptors, and a low level of CD11/CD18. The macrophages are activated by
      dissection and are present in fetal animals. Enriched macrophage cultures show a
      normal resident phenotype and remain present for weeks in dissociated muscularis
      cultures. The results also demonstrate the presence of neutrophils, monocytes,
      mast cells, and lymphocytes within the muscularis and suggest that the dense
      network of muscularis macrophages may be a potent resident trigger for
      inflammation in response to tissue injury or bacterial translocation.

PMID- 9620661
TI  - IL-4 secretion and histamine release by human basophils are differentially
      regulated by protein kinase C activation.
AB  - The role of protein kinase C (PKC) activation was investigated in the secretion
      of interleukin-4 (IL-4) protein by human basophils. Phorbol myristate acetate
      (PMA) induced little to no detectable IL-4 protein in culture supernatants,
      despite being a potent secretagogue of histamine release by basophils. In fact,
      the secretion of IL-4 by basophils stimulated with ionomycin alone was down
      regulated (30-70%) with the simultaneous addition of PMA. In peripheral blood
      lymphocytes (PBL), however, the combination of ionomycin and PMA were highly
      synergistic, resulting in maximum IL-4 release but at a slower rate. PKC
      inhibitors reversed these effects on IL-4 secretion. In sharp contrast to its
      inhibitory effect on IL-4 protein secretion, PMA did not block the accumulation
      of IL-4 mRNA in basophils activated by ionomycin. These data suggest that there
      are marked differences in the regulatory processes for IL-4 transcription,
      translation, or secretion between basophils and lymphocytes.

PMID- 9620662
TI  - Physiological activation of human neutrophils down-regulates CD53 cell surface
      antigen.
AB  - Tetraspanin transmembrane proteins have a metastasis suppressor effect by acting
      as cell motility brakes in tumor cells. CD53 is a panleukocyte antigen that
      belongs to the tetra-span superfamily. Human neutrophils express high levels of
      CD53. We tested the hypothesis that this antigen level changes when cells are
      activated. Treatment of human neutrophils with their physiological activators,
      tumor necrosis factor alpha or platelet-activating factor, resulted in down
      regulation of this antigen from the cell surface, as assessed by
      immunofluorescence flow cytometry. Similar responses were observed when
      neutrophils were stimulated with chemotactic N-formyl-methionyl-leucyl
      phenylalanine, phorbol ester, or the calcium ionophore ionomycin. The CD53
      antigen down-regulation upon neutrophil stimulation was further confirmed by
      immunoblotting analysis and was not correlated with a change in the level of CD53
      transcripts. This CD53 antigen down-regulation paralleled that of CD43 and CD44
      antigens in these cells, despite their different protein structure. The down
      regulation of the three antigens CD53, CD43, and CD44 could be inhibited by
      phenylmethylsulfonyl fluoride, suggesting that CD53 antigen down-regulation is
      the result of the activation of a proteolytic mechanism. Down-regulation of CD53
      antigen level, as a result of cellular stimulation, might play a role in the
      different aspects of neutrophil biology, by modulating its interactions on the
      cell surface.

PMID- 9620663
TI  - Gammadelta T cells present antigen to CD4+ alphabeta T cells.
AB  - Gammadelta and alphabeta TCR+ T cells share many properties and their
      interactions are likely to be coordinated and regulated. We provide evidence that
      cattle gammadelta T cells are able to present antigen to CD4+ T cells. To help
      elucidate their function gammadelta T cell lines were propagated for extensive
      characterization. Cells expressed high levels of MHC class II and production of
      co-stimulatory molecules as evidenced by the binding of a CTLA-4 fusion protein
      and synthesis of CD80 transcripts. These properties and the presence of a well
      developed endosomal compartment indicated the cells might function as antigen
      presenting cells. Resting CD4+ T cells from calves immunized with ovalbumin or
      respiratory syncytial virus-antigen proliferated in response to gammadelta T
      cells pulsed with antigen that appeared to be endocytosed via clathrin-coated
      pits or specific receptors.

PMID- 9620665
TI  - Burn-associated Candida albicans infection caused by CD30+ type 2 T cells.
AB  - Burn injury is associated with the greatly increased susceptibility of thermally
      injured patients to infection from a variety of pathogens. In this study we
      investigated the role of burn-associated type 2 T cells on the increased
      susceptibility of burned patients to Candida albicans infection using SCID mice
      and peripheral blood lymphocytes (PBL) from thermally injured patients. When SCID
      mice that were inoculated with PBL from healthy donors were resistant to C.
      albicans infection, the SCID mice that were inoculated with PBL from burned
      patients did not show any resistance to the infection. All SCID mice exposed to
      the pathogen, however, survived after inoculation with patient PBL that were
      previously depleted of CD30+ cells. The predominance of type 2 T cell responses
      was demonstrated in PBLs of thermally injured patients. As burn-associated type 2
      T cells, CD3+ CD8+ CD30+ IL-4 and IL-10-producing cells were demonstrated in
      burned patient PBL. These results suggest that burn-associated CD30+ type 2 T
      cells may play a role on the increased susceptibility of burned patients to C.
      albicans infection.

PMID- 9620664
TI  - Localization of eosinophil-derived neurotoxin and eosinophil cationic protein in
      neutrophilic leukocytes.
AB  - Eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) are
      generally regarded as eosinophil-specific proteins. We tested whether EDN and ECP
      are present in mature neutrophils. By indirect immunofluorescence, both
      eosinophils and neutrophils stained with antibodies to EDN and ECP. Lysates of
      purified (<0.1% eosinophil contamination) neutrophils contained EDN, 112+/-4
      ng/10(6) cells, and ECP, 163+/-2 ng/10(6) cells, whereas eosinophil major basic
      protein (MBP) was not detectable. Electron microscopic examination of immunogold
      labeled buffy coat cells stained with EDN antibody showed that EDN is localized
      to neutrophil granules. Finally, EDN mRNA was detected in lysates of highly
      purified neutrophils (0.001% eosinophil contamination) by the reverse
      transcription-polymerase chain reaction. We conclude that proteins that are
      either identical to or immunologically cross-reactive with EDN and ECP are
      present in neutrophils and that EDN is synthesized and localized to neutrophil
      granules. Thus, caution must be exercised in interpreting the presence of EDN and
      ECP as specific markers of eosinophil-associated inflammation in human disease.

PMID- 9620666
TI  - Differential regulation of endothelial cell adhesion molecule expression by
      nitric oxide donors and antioxidants.
AB  - Although nitric oxide (NO) and antioxidants inhibit adhesion molecule expression,
      their inhibitory effects on nuclear factor kappaB (NF-kappaB) activation may
      differ. The NO donors, but not 8-bromo-cGMP, decreased tumor necrosis factor
      alpha (TNF-alpha)-induced VCAM-1, ICAM-1, and E-selectin expression by 11-70%. In
      contrast, NAC completely abolished VCAM-1 and E-selectin expression and decreased
      ICAM-1 expression by 56%. Gel shift assays demonstrate that NF-kappaB activation
      was inhibited by both NO and antioxidants. The activation of NF-kappaB involves
      the phosphorylation and degradation of its cytoplasmic inhibitor IkappaB-alpha by
      26S proteasomes. The 26S proteasome inhibitor MG132 prevented the degradation of
      phosphorylated IkappaB-alpha. NAC inhibited IkappaB kinase (IKK) activity and
      prevented IkappaB-alpha phosphorylation and degradation. In contrast, NO did not
      inhibit IKK activity, IkappaB-alpha phosphorylation, or IkappaB-alpha
      degradation. However, NO, but not antioxidants, induced IkappaB-alpha promoter
      activity. The inhibitory effects of NO on adhesion molecule expression,
      therefore, differs from that of antioxidants in terms of the mechanism by which
      NF-kappaB is inactivated.

PMID- 9620667
TI  - Melanocortin peptides inhibit production of proinflammatory cytokines and nitric
      oxide by activated microglia.
AB  - Inflammatory processes contribute to neurodegenerative disease, stroke,
      encephalitis, and other central nervous system (CNS) disorders. Activated
      microglia are a source of cytokines and other inflammatory agents within the CNS
      and it is therefore important to control glial function in order to preserve
      neural cells. Melanocortin peptides are pro-opiomelanocortin-derived amino acid
      sequences that include alpha-melanocyte-stimulating hormone (alpha-MSH) and
      adrenocorticotropic hormone (ACTH). These peptides have potent and broad anti
      inflammatory effects. We tested effects of alpha-MSH (1-13), alpha-MSH (11-13),
      and ACTH (1-24) on production of tumor necrosis factor alpha (TNF-alpha),
      interleukin-6 (IL-6), and nitric oxide (NO) in a cultured murine microglial cell
      line (N9) stimulated with lipopolysaccharide (LPS) plus interferon gamma (IFN
      gamma). Melanocortin peptides inhibited production of these cytokines and NO in a
      concentration-related fashion, probably by increasing intracellular cAMP. When
      stimulated with LPS + IFN-gamma, microglia increased release of alpha-MSH.
      Production of TNF-alpha, IL-6, and NO was greater in activated microglia after
      innmunoneutralization of endogenous alpha-MSH. The results suggest that alpha-MSH
      is an autocrine factor in microglia. Because melanocortin peptides inhibit
      production of pro-inflammatory mediators by activated microglia they might be
      useful in treatment of inflammatory/degenerative brain disorders.

PMID- 9620668
TI  - Mast cells produce ENA-78, which can function as a potent neutrophil
      chemoattractant during allergic airway inflammation.
AB  - The inflammatory response during allergic airway inflammation involves the
      recruitment of multiple leukocyte populations, including neutrophils, monocytes,
      lymphocytes, and eosinophils. All of these populations likely contribute to the
      pathology observed during repeated episodes of allergic airway inflammation. We
      have examined the role of a human neutrophil-specific chemokine (C-x-C), ENA-78,
      in a model of allergic airway responses and identified murine mast cells as a
      cellular source of an ENA-78-like molecule. Within this allergic airway model,
      neutrophil infiltration into the airway occurs within 4-8 h post-allergen
      challenge, persists within the airway until 24 h, and resolves by 48 h post
      challenge. Neutrophil influx precedes the eosinophil infiltration, which peaks in
      the airway at 48 h post-allergen challenge. In this study the production of ENA
      78 from challenged lungs demonstrated a significant increase in the allergen-,
      but not vehicle-, challenged lungs. In vivo neutralization of ENA-78 by passive
      immunization demonstrated a significant decrease in peak neutrophil infiltration
      at 8 h, with no effect on the eosinophil infiltration at 48 h post-challenge.
      Because ENA-78 has been shown to be chemotactic for neutrophils and given the
      involvement of mast cell degranulation in allergic responses, we examined mast
      cells for the presence of ENA-78. Cultured mast cells spontaneously released ENA
      78, but on activation with IgE + antigen, NG-L-arginine methyl ester or compound
      48/80 produced significantly increased levels of ENA-78. Supernatants from
      sonicated MC-9 mast cells induced an overwhelming influx of neutrophils into the
      BAL by 4 h post-intratracheal injection into mice, suggesting that the mast cell
      is a significant source of neutrophil chemotactic factors. Mast cell supernatant
      mediated neutrophil infiltration was substantially decreased by preincubation of
      the supernatant with antibodies specific for ENA-78. These data indicate a major
      neutrophil chemotactic protein produced by mast cells during allergic responses
      may be mast cell-derived ENA-78.

PMID- 9620669
TI  - Construction and expression of a soluble form of human CD30 ligand with
      functional activity.
AB  - CD30 engagement in human lymphoid cells induces pleiotropic cellular responses
      that affect cellular viability and proliferation, cytokine production, and
      nuclear factor kappaB (NF-kappaB) nuclear translocation. Studies examining the
      molecular basis for this pleiotropism thus far have relied on the use of
      antibodies and cells transfected with CD30L to trigger CD30, two methods of
      receptor induction that present important limitations: antibodies are not
      physiological receptor-triggering molecules and CD30L transfectants induce high
      background intracellular signaling in the cells under study. We have generated
      and expressed a functional soluble human CD30L molecule (sCD30L/CD8alpha)
      comprised of the extracellular domain of human CD30L fused to the extracellular
      domain of the human CD8alpha chain. Immunoprecipitation and Western blot analysis
      of sCD30L/CD8alpha revealed the existence of at least two forms of
      sCD30L/CD8alpha, which exhibited molecular sizes consistent with the existence of
      monomeric and trimeric forms of the molecule. Binding analyses performed using a
      soluble CD30 fusion protein (sCD30/gamma1) confirmed the ability of
      sCD30L/CD8alpha to bind to CD30. Functionally, immobilized sCD30L/CD8alpha
      induced cell death in the CD30-expressing lines Karpas-299 and HDLM-2 and reduced
      proliferative levels in Karpas-299; these effects were inhibitable by the
      addition of sCD30/gamma1. These studies demonstrate the utility of
      sCD30L/CD8alpha in characterizing the normal function of CD30L and CD30 and
      indicate the natural ability of soluble forms of CD30L to trimerize.

PMID- 9620670
TI  - Hypoxia down-regulates MCP-1 expression: implications for macrophage distribution
      in tumors.
AB  - Monocyte chemoattractant protein 1 (MCP-1) is likely to contribute to the
      macrophage infiltrate in human ovarian carcinomas. Although MCP-1 is
      predominantly expressed by the tumor parenchyma, macrophages accumulate at
      highest density in necrotic regions, which are associated with low oxygen
      tensions. Tumor necrosis factor alpha (TNF-alpha) can stimulate MCP-1 production
      and is also present within ovarian carcinomas. We have investigated the effect of
      hypoxia both on MCP-1 expression in ovarian cancer cell lines and monocyte
      migration. Hypoxia down-regulated TNF-alpha-induced MCP-1 mRNA and protein
      production by ovarian cancer cells. The effect was mimicked by cobalt chloride
      and desferrioxamine, consistent with a specific oxygen-sensing mechanism. Unlike
      antioxidants, hypoxia did not inhibit nuclear factor KB mobilization. Monocyte
      migration in response to MCP-1 was also diminished under hypoxic conditions. Down
      regulation of MCP-1 expression and the inhibition of monocyte migration are
      independent effects of hypoxia that may contribute to the distribution of
      macrophages within ovarian tumors.

PMID- 9620672
TI  - CD28-mediated activation in CD45RA+ and CD45RO+ T cells: enhanced levels of
      reactive oxygen intermediates and c-Rel nuclear translocation in CD45RA+ cells.
AB  - We have analyzed the effect of complete T cell activation (anti-CD3 plus anti
      CD28) on the activation of NF-kappaB in CD45RA+ (naive) and CD45RO+
      (memory/effector) T cells. Long exposure (24 h) induced stronger NF-kappaB DNA
      binding in CD45RA+ cells than in CD45RO+ cells. Analysis of the nuclear c-Rel
      protein indicated that after anti-CD3+anti-CD28 stimulation the level of c-Rel
      was higher in CD45RA+ cells. Analysis of the cytoplasmic inhibitor IkappaBalpha
      indicated that anti-CD3+anti-CD28 stimulation induced a long-lasting degradation
      in CD45RA+ cells but in CD45RO+ cells the degradation process was more rapid.
      Because the CD28 costimulus is known to induce the production of reactive oxygen
      intermediates (ROIs), the intracellular ROI levels in CD45RA+ and CD45RO+ cells
      were compared by flow cytometry. ROIs were produced in both cell types, but more
      strongly in CD45RA+ cells. The data presented in this study further emphasize the
      differences between CD45RA+ and CD45RO+ T lymphocytes in ROI-dependent signaling
      pathways.

PMID- 9620671
TI  - Activation of cytokine production, tumoricidal properties, and tyrosine
      phosphorylation of MAPKs in human monocytes by a new synthetic lipopeptide,
      JBT3002.
AB  - We investigated the expression of cytokine genes and tumoricidal properties in
      human blood monocytes in response to a new synthetic immunomodulating
      lipopeptide, JBT3002. Incubation of peripheral blood monocytes with free-form
      JBT3002 or JBT3002 encapsulated in multilamellar phospholipid vesicles
      (liposomes, MLV-JBT3002) induced tumoricidal properties in a dose-dependent
      manner. Both MLV-JBT3002 and free-form JBT3002 induced production of tumor
      necrosis factor alpha, interleukin-1beta, and interleukin-6 in a dose-dependent
      manner with similar kinetics. Treatment of monocytes with interferon-gamma did
      not significantly alter the expression of cytokine genes but increased the
      expression of cytokines induced by MLV-JBT3002 and free-form JBT3002. In contrast
      to monocyte activation by lipopolysaccharide (LPS), activation by JBT3002 was
      independent of serum and was not inhibited by CD14-neutralizing antibody.
      Incubation of monocytes with JBT3002 induced a rapid increase in tyrosine
      phosphorylation of proteins with apparent molecular masses of 42 and 38 kDa, a
      migration band shift of c-Jun NH2-terminal kinase 1 (JNK1), and activation of
      extracellular signaling regulated kinases. Consistent with its effect on cytokine
      expression, stimulation of these intracellular signaling pathways by JBT3002 was
      not inhibited in serum-free conditions. Collectively, the data indicate that the
      synthetic lipopeptide JBT3002 is a potent monocyte activator that modulates
      monocyte function by mechanisms similar to LPS but by a distinct receptor.

PMID- 9620673
TI  - Involvement of tyrosine phosphorylation in inhibition of fMLP-induced PLD
      activation by N-acetyl-L-cysteine in differentiated HL60 cells.
AB  - N-acetyl-L-cysteine (NAC), which is known as a multipotential agent; an
      antioxidant, a thiol reagent, or a tyrosine kinase inhibitor, inhibited N-formyl
      methionyl-leucyl-phenylalanine (fMLP)-induced phospholipase D (PLD) activation in
      HL60 cells in a concentration-dependent manner (IC50 = 2 mM). Its inhibitory
      mechanism was examined in this study to gain insight into the regulation of PLD
      activity. NAC had no direct effect on membrane PLD activity in an in vitro assay
      system. fMLP-induced formation of inositol phosphates via phospholipase C (PLC)
      was not affected by the drug, suggesting that the receptor-G protein coupling was
      not inhibited. H2O2, which is known to induce PLD activation in several types of
      cells, failed to activate PLD in HL60 cells. Pretreatment of 3-amino-1,2,4
      triazole (ATZ), a catalase inhibitor, did not enhance fMLP-induced PLD
      activation. NAC inhibited fMLP-induced tyrosine phosphorylation of several
      protein bands (42, 44, 64, and 138 kDa) in a concentration-dependent manner. The
      temporal and concentration-dependent inhibitory profiles for tyrosine
      phosphorylation of 64- and 138-kDa proteins were well correlated with PLD
      activation. However, thiol reagents, 1 mM 2,3-dimercapto-l-propanol (2,3-DMP), 1
      mM dithiothreitol (DTT), and 2 mM cysteine also did not suppress protein tyrosine
      phosphorylation or PBut formation by fMLP. Wortmannin, a selective
      phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor, inhibited these two
      tyrosine phosphorylation bands. These results suggest that NAC inhibits fMLP
      induced PLD activation through blockage of protein tyrosine phosphorylation,
      which is located at the downstream of PI-3 kinase.

PMID- 9620674
TI  - HLA-B27-restricted antigen presentation in the absence of tapasin reveals
      polymorphism in mechanisms of HLA class I peptide loading.
AB  - Tapasin is a resident ER protein believed to be critical for antigen presentation
      by HLA class I molecules. We demonstrate that allelic variation in MHC class I
      molecules influences their dependence on tapasin for peptide loading and antigen
      presentation. HLA-B*2705 molecules achieve high levels of surface expression and
      present specific viral peptides in the absence of tapasin. In contrast, HLA
      B*4402 molecules are highly dependent upon human tapasin for these functions,
      while HLA-B8 molecules are intermediate in this regard. Significantly, HLA-B*2705
      like HLA-B*4402, requires tapasin to associate efficiently with TAP (transporters
      associated with antigen processing). The unusual ability of HLA-B*2705 to form
      peptide complexes without associating with TAP or tapasin confers flexibility in
      the repertoire of peptides presented by this molecule. We speculate that these
      properties might contribute to the role of HLA-B27 in conferring susceptibility
      to inflammatory spondyloarthropathies.

PMID- 9620675
TI  - A basis for alloreactivity: MHC helical residues broaden peptide recognition by
      the TCR.
AB  - The high frequency of alloreactive T cells is a major hindrance for
      transplantation; however, the molecular basis for alloreactivity remains elusive.
      We examined the I-Ep alloreactivity of a well-characterized Hb(64-76)/I-Ek
      specific murine T cell. Using a combinatorial peptide library approach, we
      identified a highly stimulatory alloepitope mimic and observed that the
      recognition of the central TCR contact residues (P3 and P5) was much more
      flexible than that seen with Hb(64-76)/I-Ek, but still specific. Therefore,
      alloreactive T cells can recognize a self-peptide/MHC surface; however, the
      allogeneic MHC molecule changes the recognition requirements for the central
      region of the peptide, allowing a more diverse repertoire of ligands to be
      recognized.

PMID- 9620676
TI  - Structural basis of 2C TCR allorecognition of H-2Ld peptide complexes.
AB  - MHC class I H-2Ld complexed with peptide QL9 (or p2Ca) is a high-affinity
      alloantigen for the 2C TCR. We used the crystal structure of H-2Ld with a mixture
      of bound peptides at 3.1 A to construct a model of the allogeneic 2C-Ld/QL9
      complex for comparison with the syngeneic 2C-Kb/dEV8 structure. A prominent ridge
      on the floor of the Ld peptide-binding groove, not present in Kb, creates a C
      terminal bulge in Ld peptides that greatly increases interactions with the 2C
      beta-chain. Furthermore, weak electrostatic complementarity between Asp77 on the
      alpha1 helix of Kb and 2C is enhanced in the allogeneic complex by closer
      proximity of QL9 peptide residue AspP8 to the 2C HV4 loop.

PMID- 9620677
TI  - Allelic inclusion of T cell receptor alpha genes poses an autoimmune hazard due
      to low-level expression of autospecific receptors.
AB  - Organ-specific autoimmune disease can be caused by alphabeta T cells that have
      escaped self-tolerance induction. Here we show that one of the causes of escape
      from self-tolerance is the coexpression of two different T cell receptors by the
      same cell, which can occur in up to 30% of all T cells in normal mice and can
      lead to low-level surface expression of an autospecific TCR. We found that double
      receptor-expressing T cells can escape tolerance even to ubiquitously expressed
      antigens but can nevertheless induce autoimmune diabetes when the relevant
      protein is expressed in pancreatic tissue. Such diabetogenic T cells are absent,
      however, among T cells expressing the autospecific TCR as the sole receptor.

PMID- 9620678
TI  - Differential tolerance is induced in T cells recognizing distinct epitopes of
      myelin basic protein.
AB  - Experimental allergic encephalomyelitis (EAE) is induced by T cell-mediated
      immunity to central nervous system antigens. In H-2u mice, EAE is mediated
      primarily by T cells specific for residues 1-11 of myelin basic protein (MBP). We
      demonstrate that differential tolerance to MBP1-11 versus epitopes in MBP121-150
      is induced by expression of endogenous MBP, reflecting extreme differences in
      stability of peptide/MHC complexes. The diverse MBP121-150-specific TCR
      repertoire can be divided into three fine specificity groups. Two groups were
      identified in wild-type mice despite extensive tolerance, but the third group was
      not detected. Activated MBP121-150-specific T cells induce EAE in wild-type mice.
      Thus, encephalitogenic T cells that escape tolerance either recognize short-lived
      peptide/MHC complexes or express TCRs with unique specificities for stable
      complexes.

PMID- 9620679
TI  - Modifications of CD8+ T cell function during in vivo memory or tolerance
      induction.
AB  - Naive monoclonal T cells specific for the male antigen can be stimulated in vivo
      to eliminate male cells and become memory cells or to permit survival of male
      cells and become tolerant. Memory cells responded to TCR ligation by cyclic
      oscillations of calcium levels and immediate secretion of very high levels of IL
      2 and interferon-gamma. Tolerant cells did not proliferate in response to
      ionomycin and phorbol myristate acetate, failing to mobilize calcium to produce
      IL-2 or express IL-2R, but survived for long time periods in vivo and secreted IL
      10. These results emphasize that tolerance is not an absence of all functional
      activity and may be associated with modifications of behavior conferring
      important regulatory functions on tolerant T cells.

PMID- 9620680
TI  - Potent and selective stimulation of memory-phenotype CD8+ T cells in vivo by IL
      15.
AB  - Proliferation of memory-phenotype (CD44hi) CD8+ cells induced by infectious
      agents can be mimicked by injection of type I interferon (IFN I) and by IFN I
      inducing agents such as lipopolysaccharide and Poly I:C; such proliferation does
      not affect naive T cells and appears to be TCR independent. Since IFN I inhibits
      proliferation in vitro, IFN I-induced proliferation of CD8+ cells in vivo
      presumably occurs indirectly through production of secondary cytokines, e.g.,
      interleukin-2 (IL-2) or IL-15. We show here that, unlike IL-2, IL-15 closely
      mimics the effects of IFN I in causing strong and selective stimulation of memory
      phenotype CD44hi CD8+ (but not CD4+) cells in vivo; similar specificity applies
      to purified T cells in vitro and correlates with much higher expression of IL
      2Rbeta on CD8+ cells than on CD4+ cells.

PMID- 9620681
TI  - TGF-beta1 alters APC preference, polarizing islet antigen responses toward a Th2
      phenotype.
AB  - TGF-beta1, expressed in the pancreatic islets, protects the nonobese diabetic
      (NOD) mouse from insulin-dependent diabetes mellitus (IDDM). The islet antigen
      specific T cell response of ins-TGF-beta1 mice relied on different antigen
      presenting cells (APC) from those used by NOD T cells. T cells from NOD mice
      utilized B cells to present islet antigen, whereas T cells from ins-TGF-beta1
      mice utilized macrophages. In addition, the islet antigen-specific T cell
      repertoire of ins-TGF-beta1 mice was distinct and deviated toward an IL-4
      producing Th2 phenotype. When ins-TGF-beta1 mice were treated with anti-iL-4
      antibody, islet antigen-specific IFNGamma-producing Th1 cells were unleashed, and
      the incidence of diabetes increased to the level of NOD mice. This suggests
      active suppression of a diabetogenic T cell response. This study describes a
      novel mechanism in which expression of TGF-beta1 in the context of self-antigen
      shifts APC preference, deviating T cell responses to a Th2 phenotype, preventing
      IDDM.

PMID- 9620682
TI  - Biochemical mechanisms of IL-2-regulated Fas-mediated T cell apoptosis.
AB  - Activation-induced cell death (AICD) of lymphocytes is an important mechanism of
      self-tolerance. In CD4+ T cells, AICD is mediated by the Fas pathway and is
      enhanced by IL-2. To define the mechanisms of this pro-apoptotic action of IL-2,
      we analyzed CD4+ T cells from wild-type and IL-2-/- mice expressing a transgenic
      T cell receptor. T cells become sensitive to AICD after activation by antigen and
      IL-2. IL-2 increases transcription and surface expression of Fas ligand (FasL)
      and suppresses transcription and expression of FLIP, the inhibitor of apoptosis.
      The ability of IL-2 to enhance expression of a pro-apoptotic molecule, FasL, and
      to suppress an inhibitor of Fas signaling, FLIP, likely accounts for the role of
      this cytokine in potentiating T cell apoptosis.

PMID- 9620683
TI  - SEK1/MKK4 is required for maintenance of a normal peripheral lymphoid compartment
      but not for lymphocyte development.
AB  - SAPK is a member of the group of evolutionary conserved stress-activated kinases
      that mediate control of cellular death and proliferation. In lymphocytes, the
      SAPK pathway has been implicated in signaling from antigen, costimulatory, and
      death receptors; SEK1, which directly activates SAPK, is required for early
      embryonic development and has also been reported to be essential for normal
      lymphocyte development. In contrast to the latter findings, we have used RAG-2
      deficient blastocyst complementation to show that SEK1-deficient embryonic stem
      cells support unimpaired T and B lymphocyte development. Moreover, mature SEK1
      deficient lymphocytes are capable of SAPK activation. Surprisingly, however,
      aging SEK1-deficient chimeric mice frequently develop lymphadenopathy and
      polyclonal B and T cell expansions. Thus, SEK1 is not required for lymphocyte
      development, but is required for maintaining peripheral lymphoid homeostasis.

PMID- 9620685
TI  - Interactions between HIV1 Nef and vacuolar ATPase facilitate the internalization
      of CD4.
AB  - CD4 is the primary receptor for the human immunodeficiency virus (HIV). Nef is an
      accessory protein of HIV that decreases the expression of CD4 on the surface of
      infected cells. In this study, we identified the Nef binding protein 1 (NBP1),
      which interacts specifically with Nef in vitro and in vivo. Since it shares
      sequence similarity with the catalytic subunit of the vacuolar ATPase (V-ATPase)
      and complements the loss of this VMA13 gene in yeast, NBP1 is the human homolog
      of Vma13p. Direct interactions between Nef and NBP1 were correlated with the
      ability of Nef to internalize CD4. The expression of the antisense NBP1 abrogated
      these effects. We conclude that NBP1 helps to connect Nef with the endocytic
      pathway.

PMID- 9620684
TI  - CD19 as a membrane-anchored adaptor protein of B lymphocytes: costimulation of
      lipid and protein kinases by recruitment of Vav.
AB  - CD19 is a coreceptor that amplifies signaling by membrane immunoglobulin (mIg) to
      promote responses of the B lymphocyte to T-dependent antigens. Vav is a guanine
      nucleotide exchange factor for the Rho, Rac, Cdc42 family of small GTPases. We
      found that coligating mIg and CD19 causes a synergistic increase in the tyrosine
      phosphorylation of CD19. Phosphorylated tyrosine-391 of CD19 binds Vav to mediate
      a sustained increase in intracellular Ca2+ concentration. This response
      correlates with activation by the CD19-Vav complex of phosphatidylinositol 4
      phosphate 5-kinase for the synthesis of phosphatidylinositol 4,5-bisphosphate.
      Interaction of CD19 with Vav also mediates the synergistic activation of the
      mitogen-activated protein kinase JNK. Therefore, CD19 is a membrane adaptor
      protein that recruits Vav for the activation of lipid and protein kinases.

PMID- 9620686
TI  - An ingenious filter: the structural basis for ion channel selectivity.

PMID- 9620687
TI  - Two for T.

PMID- 9620688
TI  - Shedding light on the biological clock.

PMID- 9620689
TI  - Multiple roles for hepatocyte growth factor in sympathetic neuron development.
AB  - We have studied the role of hepatocyte growth factor (HGF)/Met signaling in the
      development of sympathetic neuroblasts and neurons. Anti-HGF antibodies reduced
      the number of sympathetic neuroblasts that differentiated into neurons, but
      neither anti-HGF antibodies nor HGF affected neuroblast proliferation. Anti-HGF
      antibodies also reduced the survival of neuroblasts but not sympathetic neurons.
      HGF greatly enhanced the neurite outgrowth of NGF-dependent sympathetic neurons
      throughout development. These in vitro effects of anti-HGF antibodies and HGF
      were abolished by a disabling mutation of Met, the HGF receptor tyrosine kinase.
      The Met mutation also increased sympathetic neuroblast apoptosis in vivo. Because
      Met and HGF are expressed in sympathetic ganglia throughout development, it is
      possible that the multiple effects of HGF/Met signaling on sympathetic
      neuroblasts and neurons occur in part by an autocrine mechanism.

PMID- 9620690
TI  - Rapid actin-based plasticity in dendritic spines.
AB  - Dendritic spines have been proposed as primary sites of synaptic plasticity in
      the brain. Consistent with this hypothesis, spines contain high concentrations of
      actin, suggesting that they might be motile. To investigate this possibility, we
      made video recordings from hippocampal neurons expressing actin tagged with green
      fluorescent protein (GFP-actin). This reagent incorporates into actin-containing
      structures and allows the visualization of actin dynamics in living neurons. In
      mature neurons, recordings of GFP fluorescence revealed large actin-dependent
      changes in dendritic spine shape, similar to those inferred from previous studies
      using fixed tissues. Visible changes occurred within seconds, suggesting that
      anatomical plasticity at synapses can be extremely rapid. As well as providing a
      molecular basis for structural plasticity, the presence of motile actin in
      dendritic spines implicates the postsynaptic element as a primary site of this
      phenomenon.

PMID- 9620691
TI  - The polarized sorting of membrane proteins expressed in cultured hippocampal
      neurons using viral vectors.
AB  - One model of neuronal polarity (Dotti and Simons, 1990) proposes that neurons and
      polarized epithelia use similar mechanisms to sort membrane proteins. To explore
      this hypothesis, we used viral vectors to express proteins in cultured neurons
      and assessed their distribution using quantitative immunofluorescence microscopy.
      Basolateral epithelial proteins were polarized to dendrites; more significantly,
      mutations of sequences required for their basolateral targeting in epithelia also
      disrupted dendritic targeting. Unexpectedly, apical proteins were not polarized
      to axons but were expressed at roughly equal amounts in dendrites and axons.
      These data provide strong evidence that targeting of basolateral and dendritic
      proteins depends on common mechanisms. In contrast, the sorting of proteins to
      the axon requires signals that are not present in apical proteins.

PMID- 9620692
TI  - Oligodendrocyte population dynamics and the role of PDGF in vivo.
AB  - Oligodendrocyte progenitors originate near the floor plate of the spinal cord,
      then proliferate and migrate throughout the cord before giving rise to
      oligodendrocytes. Progenitor cell proliferation stops before birth because the
      cell cycle slows down, linked to an increase in differentiation and death.
      Experiments with transgenic mice show that platelet-derived growth factor (PDGF)
      drives progenitor cell division and suggest that slowing of and exit from the
      cycle reflects a decline in PDGF signaling. Overexpressing PDGF induces
      hyperproliferation of progenitor cells and excessive, ectopic production of
      oligodendrocytes. However, the superfluous oligodendrocytes die at an immature
      stage of differentiation, leaving a normal complement of myelin-forming cells.
      Therefore, cell survival controls override proliferation controls for determining
      the final number and distribution of mature oligodendrocytes.

PMID- 9620693
TI  - Dorsal spinal cord neuroepithelium generates astrocytes but not oligodendrocytes.
AB  - There is evidence that oligodendrocytes in the spinal cord are derived from a
      restricted part of the ventricular zone near the floor plate. An alternative view
      is that oligodendrocytes are generated from all parts of the ventricular zone. We
      reinvestigated glial origins by constructing chick-quail chimeras in which dorsal
      or ventral segments of the embryonic chick neural tube were replaced with
      equivalent segments of quail neural tube. Ventral grafts gave rise to both
      oligodendrocytes and astrocytes. In contrast, dorsal grafts produced astrocytes
      but not oligodendrocytes. In mixed cultures of ventral and dorsal cells, only
      ventral cells generated oligodendrocytes, whereas both ventral and dorsal cells
      generated astrocytes. Therefore, oligodendrocytes are derived specifically from
      ventral neuroepithelium, and astrocytes from both dorsal and ventral.

PMID- 9620694
TI  - A synaptic Ras-GTPase activating protein (p135 SynGAP) inhibited by CaM kinase
      II.
AB  - Ca2+ influx through N-methyl-D-aspartate- (NMDA-) type glutamate receptors plays
      a critical role in synaptic plasticity in the brain. One of the proteins
      activated by the increase in Ca2+ is CaM kinase II (CaMKII). Here, we report a
      novel synaptic Ras-GTPase activating protein (p135 SynGAP) that is a major
      component of the postsynaptic density, a complex of proteins associated with
      synaptic NMDA receptors. p135 SynGAP is almost exclusively localized at synapses
      in hippocampal neurons where it binds to and closely colocalizes with the
      scaffold protein PSD-95 and colocalizes with NMDA receptors. The Ras-GTPase
      activating activity of p135 SynGAP is inhibited by phosphorylation by CaMKII
      located in the PSD protein complex. Inhibition of p135 SynGAP by CaMKII will stop
      inactivation of GTP-bound Ras and thus could result in activation of the mitogen
      activated protein (MAP) kinase pathway in hippocampal neurons upon activation of
      NMDA receptors.

PMID- 9620695
TI  - Tomosyn: a syntaxin-1-binding protein that forms a novel complex in the
      neurotransmitter release process.
AB  - Syntaxin-1 is a component of the synaptic vesicle docking and/or membrane fusion
      soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) complex (7S
      and 20S complexes) in nerve terminals. Syntaxin-1 also forms a heterodimer with
      Munc18/n-Sec1/rbSec1 in a complex that is distinct from the 7S and 20S complexes.
      In this report, we identify a novel syntaxin-1-binding protein, tomosyn, that is
      capable of dissociating Munc18 from syntaxin-1 and forming a novel 10S complex
      with syntaxin-1, soluble N-etyhlmaleimide-sensitive factor attachment (SNAP) 25,
      and synaptotagmin. The 130 kDa isoform of tomosyn is specifically expressed in
      brain, where its distribution partly overlaps with that of syntaxin-1 in nerve
      terminals. High level expression of either syntaxin-1 or tomosyn results in a
      specific reduction in Ca2+-dependent exocytosis from PC12 cells. These results
      suggest that tomosyn is an important component in the neurotransmitter release
      process where it may stimulate SNARE complex formation.

PMID- 9620696
TI  - Two distinct pools of synaptic vesicles in single presynaptic boutons in a
      temperature-sensitive Drosophila mutant, shibire.
AB  - In a temperature-sensitive Drosophila mutant, shibire, synaptic vesicles are
      completely depleted in nerve terminals after stimulation at 34 degrees C, but
      upon returning to 22 degrees C, endocytosis resumes. In this study, synaptic
      vesicles in the boutons of nerve terminals at the mutant neuromuscular junction
      were loaded with a fluorescent dye, FM1-43, during vesicle reformation at 22
      degrees C after complete depletion at 34 degrees C. We found two distinct pools
      of synaptic vesicles, namely an exo/endo cycling pool, located in the periphery
      of the bouton, and a reserve pool, located in its center. Cytochalasin D
      treatment eliminated the reserve pool and reduced synaptic transmission evoked by
      high frequency stimulation. Thus, the reserve pool may play a crucial role for
      sustaining high frequency synaptic transmission.

PMID- 9620697
TI  - Hemispheric specialization in human dorsal frontal cortex and medial temporal
      lobe for verbal and nonverbal memory encoding.
AB  - The involvement of dorsal frontal and medial temporal regions during the encoding
      of words, namable line-drawn objects, and unfamiliar faces was examined using
      functional magnetic resonance imaging (fMRI). Robust dorsal frontal activations
      were observed in each instance, but lateralization was strongly dependent on the
      materials being encoded. Encoding of words produced left-lateralized dorsal
      frontal activation, whereas encoding of unfamiliar faces produced homologous
      right-lateralized activation. Encoding of namable objects, which are amenable to
      both verbal and nonverbal encoding, yielded bilateral dorsal frontal activation.
      A similar pattern of results was observed in the medial temporal lobe. These
      results indicate that regions in both hemispheres underlie human long-term memory
      encoding, and these regions can be engaged differentially according to the nature
      of the material being encoded.

PMID- 9620698
TI  - Human amygdala activation during conditioned fear acquisition and extinction: a
      mixed-trial fMRI study.
AB  - Echoplanar functional magnetic resonance imaging (fMRI) was used in normal human
      subjects to investigate the role of the amygdala in conditioned fear acquisition
      and extinction. A simple discrimination procedure was employed in which
      activation to a visual cue predicting shock (CS+) was compared with activation to
      another cue presented alone (CS-). CS+ and CS- trial types were intermixed in a
      pseudorandom order. Functional images were acquired with an asymmetric spin echo
      pulse sequence from three coronal slices centered on the amygdala. Activation of
      the amygdala/periamygdaloid cortex was observed during conditioned fear
      acquisition and extinction. The extent of activation during acquisition was
      significantly correlated with autonomic indices of conditioning in individual
      subjects. Consistent with a recent electrophysiological recording study in the
      rat (Quirk et al., 1997), the profile of the amygdala response was temporally
      graded, although this dynamic was only statistically reliable during extinction.
      These results provide further evidence for the conservation of amygdala function
      across species and implicate an amygdalar contribution to both acquisition and
      extinction processes during associative emotional learning tasks.

PMID- 9620699
TI  - Brain systems mediating aversive conditioning: an event-related fMRI study.
AB  - We have used event-related functional magnetic resonance imaging (fMRI) to
      characterize neural responses associated with emotional learning. Employing a
      classical conditioning paradigm in which faces were conditioned by pairing with
      an aversive tone (US), we compared responses evoked by conditioned (CS+) and
      nonconditioned (CS-) stimuli. Pairing 50% of the CS+ with the US enabled us to
      constrain our analysis to responses evoked by a CS+ not followed by a US.
      Differential evoked responses, related to conditioning, were found in the
      anterior cingulate and the anterior insula, regions with known involvement in
      emotional processing. Differential responses of the amygdalae were best
      characterized by a time by stimulus interaction indicating a rapid adaptation of
      CS+-specific responses in this region.

PMID- 9620700
TI  - Efficient discrimination of temporal patterns by motion-sensitive neurons in
      primate visual cortex.
AB  - Although motion-sensitive neurons in macaque middle temporal (MT) area are
      conventionally characterized using stimuli whose velocity remains constant for 1
      3 s, many ecologically relevant stimuli change on a shorter time scale (30-300
      ms). We compared neuronal responses to conventional (constant-velocity) and time
      varying stimuli in alert primates. The responses to both stimulus ensembles were
      well described as rate-modulated Poisson processes but with very high precision
      (approximately 3 ms) modulation functions underlying the time-varying responses.
      Information-theoretic analysis revealed that the responses encoded only
      approximately 1 bit/s about constant-velocity stimuli but up to 29 bits/s about
      the time-varying stimuli. Analysis of local field potentials revealed that part
      of the residual response variability arose from "noise" sources extrinsic to the
      neuron. Our results demonstrate that extrastriate neurons in alert primates can
      encode the fine temporal structure of visual stimuli.

PMID- 9620701
TI  - Extreme diversity among amacrine cells: implications for function.
AB  - We report a quantitative survey of the population of amacrine cells present in
      the retina of the rabbit. The cells' dendritic shape and level of stratification
      were visualized by a photochemical method in which a fluorescent product was
      created within an individual cell by focal irradiation of that cell's nucleus. A
      systematically random sample of 261 amacrine cells was examined. Four previously
      known amacrine cells were revealed at their correct frequencies. Our central
      finding is that the heterogeneous collection of other amacrine cells is broadly
      distributed among at least 22 types: only one type of amacrine cell makes up more
      than 5% of the total amacrine cell population. With these results, the program of
      identification and classification of retinal neurons begun by Cajal is nearing
      completion. The complexity encountered has implications both for the retina and
      for the many regions of the central nervous system where less is known.

PMID- 9620702
TI  - How many subtypes of inhibitory cells in the hippocampus?
AB  - Hippocampal inhibitory cells are diverse. It is supposed that they fall into
      functionally distinct subsets defined by a similar morphology and physiology.
      Switching between functions could be accomplished by activating receptors for
      modulating transmitters expressed selectively by different subsets of
      interneurons. We tested this hypothesis by comparing morphology, physiology, and
      neurotransmitter receptor expression for CA1 hippocampal interneurons. We
      distinguished 16 distinct morphological phenotypes and 3 different modes of
      discharge. Subsets of inhibitory cells were excited or inhibited by agonists at
      receptors for noradrenaline, muscarine, serotonin, and mGluRs. Most cells
      responded to 2 or 3 agonists, and 25 different response combinations were
      detected. Subsets defined by morphology, physiology, and receptor expression did
      not coincide, suggesting that hippocampal interneurons cannot easily be
      segregated into a few well-defined groups.

PMID- 9620703
TI  - A novel inward rectifier K+ channel with unique pore properties.
AB  - We have cloned a novel K+-selective, inward rectifier channel that is widely
      expressed in brain but is especially abundant in the Purkinje cell layer of the
      cerebellum and pyramidal cells of the hippocampus. It is also present in a wide
      array of tissues, including kidney and intestine. The channel is only 38%
      identical to its closest relative, Kir1.3 (Kir1-ATP-regulated inward rectifier K+
      [ROMK] family) and displays none of the functional properties unique to the ROMK
      class. Kir7.1 has several unique features, including a very low estimated single
      channel conductance (approximately 50 fS), low sensitivity to block by external
      Ba2+ and Cs+, and no dependence of its inward rectification properties on the
      internal blocking particle Mg2+. The unusual pore properties of Kir7.1 seem to be
      explained by amino acids in the pore sequence that differ from corresponding
      conserved residues in all other Kir channel proteins. Replacement of one of these
      amino acids (Met-125) with the Arg absolutely conserved in all other Kir channels
      dramatically increases its single channel conductance and Ba2+ sensitivity. This
      channel would provide a steady background K+ current to help set the membrane
      potential in cells in which it is expressed. We propose that the novel channel be
      assigned to a new Kir subfamily, Kir7.1.

PMID- 9620704
TI  - Metabotropic glutamate receptor-mediated control of neurotransmitter release.
AB  - Presynaptic metabotropic glutamate receptors (mGluRs) modulate the release of
      transmitter from most central synapses. However, difficulties in recording from
      presynaptic structures has lead to an incomplete understanding of the mechanisms
      underlying these fundamental processes. By recording directly from presynaptic
      reticulospinal axons and postsynaptic motoneurons of the lamprey spinal cord, we
      have obtained electrophysiological and optical evidence that vertebrate
      presynaptic metabotropic glutamate receptors modulate neurotransmitter release at
      this synapse through two distinct mechanisms: (1) mGluR activation in the
      presynaptic terminal depresses transmitter release by activating a presynaptic K+
      current, and (2) mGluR activation enhances transmitter release by amplifying the
      action potential-evoked presynaptic Ca2+ signal by rapidly releasing Ca2+ from
      intracellular stores in a Ca2+-dependent manner. Furthermore, this effect is
      mediated by physiological release of glutamate from the presynaptic terminals.
      These autoreceptor-mediated processes are likely to generate complex effects on
      transmitter release evoked by repetitive stimulation.

PMID- 9620706
TI  - Preferential closed-state inactivation of neuronal calcium channels.
AB  - We have investigated the inactivation mechanism of neuronal N-, P/Q-, and R-type
      calcium channels. Although channels inactivate slowly during square-pulse
      depolarization, as observed previously, we now find that they inactivate
      profoundly during a train of action potential (AP) waveforms. The apparent
      paradox arises from a voltage-dependent mechanism in which channels inactivate
      preferentially from intermediate closed states along the activation pathway.
      Inactivation can therefore extend beyond the brief duration of AP waveforms to
      continue between spikes, as the channel undergoes repetitive cycles of activation
      and deactivation. The extent of inactivation during a train is strongly affected
      by the subunit composition of channels. Preferential closed-state inactivation of
      neuronal calcium channels could produce widely variable depression of Ca2+ entry
      during a train of APs.

PMID- 9620705
TI  - Primary structure and function of an A kinase anchoring protein associated with
      calcium channels.
AB  - Rapid, voltage-dependent potentiation of skeletal muscle L-type calcium channels
      requires phosphorylation by cAMP-dependent protein kinase (PKA) anchored via an A
      kinase anchoring protein (AKAP). Here we report the isolation, primary sequence
      determination, and functional characterization of AKAP15, a lipid-anchored
      protein of 81 amino acid residues with a single amphipathic helix that binds PKA.
      AKAP15 colocalizes with L-type calcium channels in transverse tubules and is
      associated with L-type calcium channels in transfected cells. A peptide fragment
      of AKAP15 encompassing the RII-binding domain blocks voltage-dependent
      potentiation. These results indicate that AKAP15 targets PKA to the calcium
      channel and plays a critical role in voltage-dependent potentiation and
      regulation of skeletal muscle contraction. The expression of AKAP15 in the brain
      and heart suggests that it may mediate rapid PKA regulation of L-type calcium
      channels in neurons and cardiac myocytes.

PMID- 9620708
TI  - Exporting tobacco addiction from the USA.

PMID- 9620707
TI  - Nitric oxide as an autocrine regulator of sodium currents in baroreceptor
      neurons.
AB  - Arterial baroreceptors are mechanosensitive nerve endings in the aortic arch and
      carotid sinus that play a critical role in acute regulation of arterial blood
      pressure. A previous study has shown that nitric oxide (NO) or NO-related species
      suppress action potential discharge of baroreceptors. In the present study, we
      investigated the effects of NO on Na+ currents of isolated baroreceptor neurons
      in culture. Exogenous NO donors inhibited both tetrodotoxin (TTX) -sensitive and 
      insensitive Na+ currents. The inhibition was not mediated by cGMP but by NO
      interaction with channel thiols. Acute inhibition of NO synthase increased the
      Na+ currents. NO scavengers (hemoglobin and ferrous diethyldithiocarbamate)
      increased Na+ currents before but not after inhibition of NO synthase.
      Furthermore, NO production in the neuronal cultures was detected by
      chemiluminescence and immunoreactivity to the neuronal isoform of NO synthase was
      identified in fluorescently identified baroreceptor neurons. These results
      indicate that NO/NO-related species function as autocrine regulators of Na+
      currents in baroreceptor neurons. Modulation of Na+ channels may represent a
      novel response to NO.

PMID- 9620709
TI  - Are angiostatin and endostatin cures for cancer?

PMID- 9620710
TI  - Sildenafil: medical advance or media event?

PMID- 9620711
TI  - Pneumococcal vaccine: time for another controlled trial.

PMID- 9620712
TI  - Misuse of psychiatric epidemiology.

PMID- 9620713
TI  - Changes in physical activity, mortality, and incidence of coronary heart disease
      in older men.
AB  - BACKGROUND: We studied the relations between physical activity and changes in
      physical activity, all-cause mortality, and incidence of major coronary-heart
      disease events in older men. METHODS: In 1978-80 (Q1), 7735 men aged 40-59 were
      selected from general practices in 24 British towns, and enrolled in a
      prospective study of cardiovascular disease, which included physical activity
      data. In 1992 (Q92), 12-14 years later, 5934 of the men (91% of available
      survivors, mean age 63 years) gave further information on physical activity and
      were then followed up for a further 4 years. The main endpoints were all-cause
      mortality during 4 years of follow-up from Q92, and major fatal and non-fatal
      coronary-heart-disease events during 3 years of follow-up from Q92. FINDINGS:
      Among 4311 men with no history of coronary heart disease, stroke, or "other heart
      trouble" by Q92 and who did not report "poor health", there were 219 deaths. In
      the inactive/occasionally active, light, moderate, and moderately
      vigorous/vigorous activity groups there were 101 (18.5/1000 person-years) 48
      (11.4), 23 (7.3), and 47 (9.1) deaths, respectively (adjusted risk ratios 1.00,
      0.61 [95% CI 0.48-0.86], 0.50 [0.31-0.79], 0.65 [0.45-0.94]). Men who were
      sedentary at Q1 and who began at least light activity by Q92 had significantly
      lower all-cause mortality than those who remained sedentary, even after
      adjustment for potential confounders (risk ratio=0.55 [0.36-0.84]). Physical
      activity improved both cardiovascular mortality (0.66 [0.35-1.23]) and non
      cardiovascular mortality (0.48 [0.27-0.85]). The relation between physical
      activity at Q92, changes in physical activity, and mortality were similar for men
      with pre-existing cardiovascular disease. INTERPRETATION: Maintaining or taking
      up light or moderate physical activity reduces mortality and heart attacks in
      older men with and without diagnosed cardiovascular disease. Our results support
      public-health recommendations for older sedentary people to increase physical
      activity, and for active middle-aged people to continue their activity into old
      age.

PMID- 9620714
TI  - Effects of a refugee-assistance programme on host population in Guinea as
      measured by obstetric interventions.
AB  - BACKGROUND: Since 1990, 500000 people have fled from Liberia and Sierra Leone to
      Guinea, west Africa, where the government allowed them to settle freely, and
      provided medical assistance. We assessed whether the host population gained
      better access to hospital care during 1988-96. METHODS: In Gueckedou prefecture,
      we used data on major obstetric interventions performed in the district hospital
      between January, 1988, and August, 1996, and estimated the expected number of
      births to calculate the rate of major obstetric interventions for the host
      population. We calculated rates for 1988-90, 1991-93, and 1994-96 for three rural
      areas with different numbers of refugees. FINDINGS: Rates of major obstetric
      interventions for the host population increased from 0.03% (95% CI 0-0.09) to
      1.06% (0.74-1.38) in the area with high numbers of refugees, from 0.34% (0.22
      0.45) to 0.92% (0.74-1.11) in the area with medium numbers, and from 0.07% (0
      0.17) to 0.27% (0.08-0.46) in the area with low numbers. The rate ratio over time
      was 4.35 (2.64-7.15), 1.70 (1.40-2.07), and 1.94 (0.97-3.87) for these areas,
      respectively. The rates of major obstetric interventions increased significantly
      more in the area with high numbers of refugees than in the other two areas.
      INTERPRETATION: In areas with high numbers of refugees, the refugee-assistance
      programme improved the health system and transport infrastructure. The presence
      of refugees also led to economic changes and a "refugee-induced demand". The non
      directive refugee policy in Guinea made such changes possible and may be a cost
      effective alternative to camps.

PMID- 9620715
TI  - Exanthematous disease induced by toxic shock syndrome toxin 1 in the early
      neonatal period.
AB  - BACKGROUND: We have seen a number of patients who developed systemic exanthema
      and thrombocytopenia in the first week of life. Although nearly 100% of the
      patients were carriers of meticillin-resistant Staphylococcus aureus (MRSA), no
      clear link between MRSA and this exanthematous disease has yet been made.
      METHODS: 20 neonates with exanthema and thrombocytopenia were selected for study.
      To see whether superantigenic exotoxins from MRSA are involved in the pathogensis
      of the exanthematous disease, we studied the production of these exotoxins by
      MRSA isolates from the neonates. We studied the expression of T-cell-receptor
      Vbeta and CD45RO in T cells taken from four of the neonates. We also analysed the
      DNA sequences of 16 cloned Vbeta2-positive T-cell-receptor-chain genes taken from
      two of the neonates. FINDINGS: Although most of the patients recovered within 5
      days of onset of the exanthematous disease without any active treatment, two
      preterm infants died in the recovery phase. All patients showed colonisation by
      MRSA. The MRSA produced toxic shock syndrome toxin-1 (TSST-1). The number of T
      cells positive for T-cell-receptor Vbeta2, reactive to TSST-1, was increased in
      the four patients studied (p<0.0001), and these T cells expressed CD45RO
      (p=0.0185). None of the Vbeta2 clones had the same junctional sequences.
      INTERPRETATION: The polyclonal expansion of Vbeta2-positive T cells in patients
      colonised by TSST-1-producing MRSA suggests that the pathogenic micro-organism of
      this neonatal exanthematous disease is S aureus, mainly MRSA, and that in its
      pathogenesis it activates T cells by TSST-1. Although the pathogenesis of both
      this exanthematous disease and toxic shock syndrome are fundamentally the same, a
      diagnosis of toxic shock syndrome cannot be made in this case, based on the
      clinical criteria for toxic shock syndrome. We propose neonatal toxic-shock
      syndrome-like exanthematous disease (NTED) as the name for this disease.

PMID- 9620716
TI  - Detection of retroviral antibodies in primary biliary cirrhosis and other
      idiopathic biliary disorders.
AB  - BACKGROUND: Retroviruses have been implicated in the aetiology of various
      autoimmune diseases. We used immunoblots as a surrogate test to find out whether
      retroviruses play a part in the development of primary biliary cirrhosis.
      METHODS: We did western blot tests for HIV-1 and the human intracisternal A-type
      particle (HIAP), on serum samples from 77 patients with primary biliary
      cirrhosis, 126 patients with chronic liver disease, 48 patients with systemic
      lupus erythematosus, and 25 healthy volunteers. FINDINGS: HIV-1 p24 gag
      seroreactivity was found in 27 (35%) of 77 patients with primary biliary
      cirrhosis, 14 (29%) of 48 patients with systemic lupus erythematosus, 14 (50%) of
      28 patients with chronic viral hepatitis, and nine (39%) of 23 patients with
      either primary sclerosing cholangitis or biliary atresia, compared with only one
      (4%) of 24 patients with alcohol-related liver disease or alpha1-antitrypsin
      deficiency liver disease, and only one (4%) of 25 healthy volunteers (p=0.003).
      Western blot reactivity to more than two HIAP proteins was found in 37 (51%) of
      patients with primary biliary cirrhosis, in 28 (58%) of patients with systemic
      lupus erythematosus, in 15 (20%) of patients with chronic viral hepatitis, and in
      four (17%) of those with other biliary diseases. None of the 23 patients with
      either alcohol-related liver disease or alpha1-antitrypsin deficiency, and only
      one of the healthy controls showed the same reactivity to HIAP proteins
      (p<0.0001). Our results showed a strong association between HIAP seroreactivity
      and the detection of autoantibodies to double-stranded DNA. HIAP seroreactivity
      was also strongly associated with the detection of mitochondrial, nuclear, and
      extractable nuclear antigens. INTERPRETATION: The HIV-1 and HIAP antibody
      reactivity found in patients with primary biliary cirrhosis and other biliary
      disorders may be attributable either to an autoimmune response to antigenically
      related cellular proteins or to an immune response to uncharacterised viral
      proteins that share antigenic determinants with these retroviruses.

PMID- 9620717
TI  - Congenital abnormalities in Brazilian children associated with misoprostol misuse
      in first trimester of pregnancy.
AB  - BACKGROUND: Misoprostol is commonly used to induce abortion in Brazil, and in
      other countries in South and Central America where abortions are illegal.
      However, misoprostol is not very effective in inducing abortions, and exposure to
      the drug in utero can cause abnormalities in the fetus. We aimed to define the
      common phenotypical effects of exposure to the drug. METHODS: We studied 42
      infants from Sao Paulo, Brazil, who were exposed to misoprostol during the first
      3 months of gestation, and then born with congenital abnormalities. We
      interviewed each of the infants' mothers to find out about misoprostol exposure
      and dosage. Each infant was physically examined by a geneticist or a
      neuropaediatrician. FINDINGS: 17 of the infants had equinovarus with cranial
      nerve defects. Ten children had equinovarus as part of more extensive
      arthrogryposis. The most distinctive phenotypes were arthrogryposis confined to
      the legs (five cases) and terminal transverse-limb defects (nine cases) with or
      without Mobius sequence. The most common dose of misoprostol taken was 800 microg
      (range 200-16000 microg). INTERPRETATION: Deformities attributed to vascular
      disruption were found in these children. We suggest that the uterine contractions
      induced by misoprostol cause vascular disruption in the fetus, including brain
      stem ischaemia. Information on the effects of taking misoprostol during pregnancy
      should be made more widely available, to dissuade women from misusing the drug.

PMID- 9620718
TI  - A man with a leg-vein clot and colonic ulcers.

PMID- 9620719
TI  - Molecular assays for surveillance of antifolate-resistant malaria.

PMID- 9620720
TI  - Sensitivity of malaria parasites to nitric oxide at low oxygen tensions.

PMID- 9620721
TI  - Parkinsonian signs and mortality from Alzheimer's disease.

PMID- 9620722
TI  - Failure of co-trimoxazole in Pneumocystis carinii infection and mutations in
      dihydropteroate synthase gene.

PMID- 9620723
TI  - CCR2-64I allele and genotype association with delayed AIDS progression in African
      women. University of Nairobi Collaboration for HIV Research.

PMID- 9620724
TI  - Low frequency of lymph-node metastasis in BRCA1-associated breast cancer.

PMID- 9620725
TI  - Left-handedness and premature death.

PMID- 9620727
TI  - Elaine Showalter: hysteria's historian.

PMID- 9620728
TI  - Rapid rise for US health-care costs, yet again.

PMID- 9620729
TI  - Child-health services beleagured in Ireland.

PMID- 9620730
TI  - Compensation vote sends message to US haemophiliacs with HIV.

PMID- 9620731
TI  - MERLIN--why we need another hero. Medical Emergency Relief International.

PMID- 9620732
TI  - Hepatitis A.

PMID- 9620733
TI  - The case for "presumed consent" in organ donation. International Forum for
      Transplant Ethics.

PMID- 9620734
TI  - Health research in the tropics.

PMID- 9620735
TI  - Increase in US medication-error deaths.

PMID- 9620736
TI  - Increase in US medication-error deaths.

PMID- 9620737
TI  - Increase in US medication-error deaths.

PMID- 9620738
TI  - Lack of efficacy of neutral endopeptidase inhibitor ecadotril in heart failure.
      The International Ecadotril Multi-centre Dose-ranging Study Investigators.

PMID- 9620739
TI  - Familial Mediterranean fever.

PMID- 9620740
TI  - Familial Mediterranean fever.

PMID- 9620741
TI  - Active versus expectant management of third stage of labour.

PMID- 9620742
TI  - Active versus expectant management of third stage of labour.

PMID- 9620743
TI  - Active versus expectant management of third stage of labour.

PMID- 9620744
TI  - Ribavirin and immune thrombocytopenic purpura.

PMID- 9620745
TI  - Familial recurrence of transposition of the great arteries.

PMID- 9620746
TI  - Magnetic-resonance imaging for breast cancer.

PMID- 9620747
TI  - First-trimester transabdominal fetal echocardiography.

PMID- 9620748
TI  - Severe childhood asthma.

PMID- 9620749
TI  - Taiwan: where do unrepresented nations stand without WHO?

PMID- 9620750
TI  - Patient's understanding of clinical trials.

PMID- 9620751
TI  - Graduate medical schools.

PMID- 9620753
TI  - Safe motherhood.

PMID- 9620752
TI  - Graduate medical schools.

PMID- 9620754
TI  - A doctor's encounter with Turner.

PMID- 9620756
TI  - Be fruitful and immortalize.

PMID- 9620757
TI  - Radicals r'aging.

PMID- 9620758
TI  - Mind the GAP, Rho, Rab and GDI.

PMID- 9620759
TI  - A chilled-out knockout.

PMID- 9620760
TI  - A sugar fix for bone tumours?

PMID- 9620761
TI  - HUGO's midlife crisis: life begins at 40.

PMID- 9620762
TI  - A putative gene causes variability in lifespan among genotypically identical
      mice.

PMID- 9620763
TI  - Accelerated accumulation of somatic mutations in the senescence-accelerated
      mouse.

PMID- 9620764
TI  - Mutant myosin VIIa causes defective melanosome distribution in the RPE of shaker
      1 mice.

PMID- 9620765
TI  - Ile50Val variant of IL4R alpha upregulates IgE synthesis and associates with
      atopic asthma.

PMID- 9620766
TI  - Translocations, cancer and the puzzle of specificity.
AB  - The finding of acquired chromosomal translocations that are consistently
      associated with specific tumour types supports the premise of lineage-specific
      mechanisms of tumorigenesis. We review the evidence indicating that the
      specificity of these translocations and the corresponding gene fusions is related
      to biological constraints at the level of recombination, expression, and protein
      function. A dynamic relationship between the gene fusion and the cellular
      environment is proposed in which the environment influences the selection of
      oncogenic fusions and the oncogenic fusion in turn influences the cellular
      environment.

PMID- 9620767
TI  - Mutations in the homeobox gene HESX1/Hesx1 associated with septo-optic dysplasia
      in human and mouse.
AB  - During early mouse development the homeobox gene Hesx1 is expressed in
      prospective forebrain tissue, but later becomes restricted to Rathke's pouch, the
      primordium of the anterior pituitary gland. Mice lacking Hesx1 exhibit variable
      anterior CNS defects and pituitary dysplasia. Mutants have a reduced
      prosencephalon, anopthalmia or micropthalmia, defective olfactory development and
      bifurcations in Rathke's pouch. Neonates exhibit abnormalities in the corpus
      callosum, the anterior and hippocampal commissures, and the septum pellucidum. A
      comparable and equally variable phenotype in humans is septo-optic dysplasia
      (SOD). We have cloned human HESX1 and screened for mutations in affected
      individuals. Two siblings with SOD were homozygous for an Arg53Cys missense
      mutation within the HESX1 homeodomain which destroyed its ability to bind target
      DNA. These data suggest an important role for Hesx1/HESX1 in forebrain, midline
      and pituitary development in mouse and human.

PMID- 9620768
TI  - Mutations in GDI1 are responsible for X-linked non-specific mental retardation.
AB  - Rab GDP-dissociation inhibitors (GDI) are evolutionarily conserved proteins that
      play an essential role in the recycling of Rab GTPases required for vesicular
      transport through the secretory pathway. We have found mutations in the GDI1 gene
      (which encodes uGDI) in two families affected with X-linked non-specific mental
      retardation. One of the mutations caused a non-conservative substitution (L92P)
      which reduced binding and recycling of RAB3A, the second was a null mutation. Our
      results show that both functional and developmental alterations in the neuron may
      account for the severe impairment of learning abilities as a consequence of
      mutations in GDI1, emphasizing its critical role in development of human
      intellectual and learning abilities.

PMID- 9620769
TI  - The forkhead transcription factor gene FKHL7 is responsible for glaucoma
      phenotypes which map to 6p25.
AB  - A number of different eye disorders with the presence of early-onset glaucoma as
      a component of the phenotype have been mapped to human chromosome 6p25. These
      disorders have been postulated to be either allelic to each other or associated
      with a cluster of tightly linked genes. We have identified two primary congenital
      glaucoma (PCG) patients with chromosomal anomalies involving 6p25. In order to
      identify a gene involved in PCG, the chromosomal breakpoints in a patient with a
      balanced translocation between 6p25 and 13q22 were cloned. Cloning of the 6p25
      breakpoint led to the identification of two candidate genes based on proximity to
      the breakpoint. One of these, FKHL7, encoding a forkhead transcription factor, is
      in close proximity to the breakpoint in the balanced translocation patient and is
      deleted in a second PCG patient with partial 6p monosomy. Furthermore, FKHL7 was
      found to harbour mutations in patients diagnosed with Rieger anomaly (RA),
      Axenfeld anomaly (AA) and iris hypoplasia (IH). This study demonstrates that
      mutations in FKHL7 cause a spectrum of glaucoma phenotypes.

PMID- 9620770
TI  - Chaperone suppression of aggregation and altered subcellular proteasome
      localization imply protein misfolding in SCA1.
AB  - Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative
      disorder caused by expansion of a polyglutamine tract in ataxin-1. In affected
      neurons of SCA1 patients and transgenic mice, mutant ataxin-1 accumulates in a
      single, ubiquitin-positive nuclear inclusion. In this study, we show that these
      inclusions stain positively for the 20S proteasome and the molecular chaperone
      HDJ-2/HSDJ. Similarly, HeLa cells transfected with mutant ataxin-1 develop
      nuclear aggregates which colocalize with the 20S proteasome and endogenous HDJ
      2/HSDJ. Overexpression of wild-type HDJ-2/HSDJ in HeLa cells decreases the
      frequency of ataxin-1 aggregation. These data suggest that protein misfolding is
      responsible for the nuclear aggregates seen in SCA1, and that overexpression of a
      DnaJ chaperone promotes the recognition of a misfolded polyglutamine repeat
      protein, allowing its refolding and/or ubiquitin-dependent degradation.

PMID- 9620771
TI  - Severe early-onset obesity, adrenal insufficiency and red hair pigmentation
      caused by POMC mutations in humans.
AB  - Sequential cleavage of the precursor protein pre-pro-opiomelanocortin (POMC)
      generates the melanocortin peptides adrenocorticotrophin (ACTH), melanocyte
      stimulating hormones (MSH) alpha, beta and gamma as well as the opioid-receptor
      ligand beta-endorphin. While a few cases of isolated ACTH deficiency have been
      reported (OMIM 201400), an inherited POMC defect has not been described so far.
      Recent studies in animal models elucidated a central role of alpha-MSH in the
      regulation of food intake by activation of the brain melanocortin-4-receptor (MC4
      R; refs 3-5) and the linkage of human obesity to chromosome 2 in close proximity
      to the POMC locus, led to the proposal of an association of POMC with human
      obesity. The dual role of alpha-MSH in regulating food intake and influencing
      hair pigmentation predicts that the phenotype associated with a defect in POMC
      function would include obesity, alteration in pigmentation and ACTH deficiency.
      The observation of these symptoms in two probands prompted us to search for
      mutations within their POMC genes. Patient 1 was found to be a compound
      heterozygote for two mutations in exon 3 (G7013T, C7133delta) which interfere
      with appropriate synthesis of ACTH and alpha-MSH. Patient 2 was homozygous for a
      mutation in exon 2 (C3804A) which abolishes POMC translation. These findings
      represent the first examples of a genetic defect within the POMC gene and define
      a new monogenic endocrine disorder resulting in early-onset obesity, adrenal
      insufficiency and red hair pigmentation.

PMID- 9620772
TI  - The putative tumour suppressor EXT1 alters the expression of cell-surface heparan
      sulfate.
AB  - Hereditary multiple exostoses (HME) is an autosomal dominant disorder
      characterized by the formation of cartilage-capped tumours (exostoses) that
      develop from the growth plate of endochondral bone. This condition can lead to
      skeletal abnormalities, short stature and malignant transformation of exostoses
      to chondrosarcomas or osteosarcomas. Linkage analyses have identified three
      different genes for HME, EXT1 on 8q24.1, EXT2 on 11p11-13 and EXT3 on 19p (refs 6
      9). Most HME cases have been attributed to missense or frameshift mutations in
      these tumour-supressor genes, whose functions have remained obscure. Here, we
      show that EXT1 is an ER-resident type II transmembrane glycoprotein whose
      expression in cells results in the alteration of the synthesis and display of
      cell surface heparan sulfate glycosaminoglycans (GAGs). Two EXT1 variants
      containing aetiologic missense mutations failed to alter cell-surface
      glycosaminoglycans, despite retaining their ER-localization.

PMID- 9620773
TI  - Impaired stress response and reduced anxiety in mice lacking a functional
      corticotropin-releasing hormone receptor 1.
AB  - Corticotropin-releasing hormone (CRH) is a potent mediator of endocrine,
      autonomic, behavioural and immune responses to stress, and has been implicated in
      the stress-like and other aversive consequences of drug abuse, such as withdrawal
      from alcohol. Two CRH receptors, Crhr1 and Crhr2, have been identified in the
      mouse. Crhr1 is highly expressed in the anterior pituitary, neocortex,
      hippocampus, amygdala and cerebellum, and activation of this receptor stimulates
      adenylate cyclase. Here we show that in mice lacking Crhr1, the medulla of the
      adrenal gland is atrophied and stress-induced release of adrenocorticotropic
      hormone (ACTH) and corticosterone is reduced. The homozygous mutants exhibit
      increased exploratory activity and reduced anxiety-related behaviour under both
      basal conditions and following alcohol withdrawal. Our results demonstrate a key
      role of the Crhr1 receptor in mediating the stress response and anxiety-related
      behaviour.

PMID- 9620774
TI  - A novel homeobox gene PITX3 is mutated in families with autosomal-dominant
      cataracts and ASMD.
AB  - We report here the identification of a new human homeobox gene, PITX3, and its
      involvement in anterior segment mesenchymal dysgenesis (ASMD) and congenital
      cataracts in humans. The PITX3 gene is the human homologue of the mouse Pitx3
      gene and is a member of the RIEG/PITX homeobox gene family. The protein encoded
      by PITX3 shows 99% amino-acid identity to the mouse protein, with 100% identity
      in the homeodomain and approximately 70% overall identity to other members of
      this family. We mapped the human PITX3 gene to 10q25 using a radiation-hybrid
      panel. A collection of 80 DNA samples from individuals with various eye anomalies
      was screened for mutations in the PITX3 gene. We identified two mutations in
      independent patients. A 17-bp insertion in the 3'-end of the coding sequence,
      resulting in a frame shift, occurred in a patient with ASMD and cataracts, and a
      G-->A substitution, changing a codon for serine into a codon for asparagine, in
      the 5'-end of the gene occurred in a patient with congenital cataracts. Both
      mutations cosegregate with the disease phenotype in families, and neither were
      found in up to 300 control individuals studied. Further expression analysis of
      Pitx3 in the mouse supports a unique role in early ocular development, with later
      expression extending to the midbrain, tongue, incisors, sternum, vertebrae and
      limbs. These data strongly suggest a role for PITX3 in ASMD and cataracts and
      provide new evidence of the contribution of the RIEG/PITX gene family to the
      developmental program underpinning normal eye formation.

PMID- 9620775
TI  - Extension of Drosophila lifespan by overexpression of human SOD1 in motorneurons.
AB  - Reactive oxygen (RO) has been identified as an important effector in ageing and
      lifespan determination. The specific cell types, however, in which oxidative
      damage acts to limit lifespan of the whole organism have not been explicitly
      identified. The association between mutations in the gene encoding the oxygen
      radical metabolizing enzyme CuZn superoxide dismutase (SOD1) and loss of
      motorneurons in the brain and spinal cord that occurs in the life-shortening
      paralytic disease, Familial Amyotrophic Lateral Sclerosis (FALS; ref. 4),
      suggests that chronic and unrepaired oxidative damage occurring specifically in
      motor neurons could be a critical causative factor in ageing. To test this
      hypothesis, we generated transgenic Drosophila which express human SOD1
      specifically in adult motorneurons. We show that overexpression of a single gene,
      SOD1, in a single cell type, the motorneuron, extends normal lifespan by up to
      40% and rescues the lifespan of a short-lived Sod null mutant. Elevated
      resistance to oxidative stress suggests that the lifespan extension observed in
      these flies is due to enhanced RO metabolism. These results show that SOD
      activity in motorneurons is an important factor in ageing and lifespan
      determination in Drosophila.

PMID- 9620776
TI  - ATM-dependent activation of p53 involves dephosphorylation and association with
      14-3-3 proteins.
AB  - The p53 tumour-suppressor protein is a sequence-specific DNA-binding
      transcription factor that induces cell cycle arrest or apoptosis in response to
      genotoxic stress. Activation of p53 by DNA-damaging agents is critical for
      eliminating cells with damaged genomic DNA and underlies the apoptotic response
      of human cancers treated with ionizing radiation (IR) and radiomimetic drugs. The
      molecular mechanisms by which DNA damage activates p53 have not been elucidated.
      Both the levels of p53 protein and its affinity for specific DNA sequences
      increase in response to genotoxic stress. In vitro, the affinity of p53 for DNA
      is regulated by its carboxy-terminus. We therefore examined whether this region
      of p53 is targeted by DNA-damage signalling pathways in vivo. In nonirradiated
      cells, serines 376 and 378 of p53 were phosphorylated. IR led to
      dephosphorylation of Ser376, creating a consensus binding site for 14-3-3
      proteins and leading to association of p53 with 14-3-3. In turn, this increased
      the affinity of p53 for sequence-specific DNA. Consistent with the lack of p53
      activation by IR in ataxia telangiectasia (AT; refs 14,15), neither Ser376
      dephosphorylation, nor the interaction of p53 with 14-3-3 proteins occurred in AT
      cells.

PMID- 9620777
TI  - Positional cloning of the gene for Nijmegen breakage syndrome.
AB  - Nijmegen breakage syndrome (NBS), also known as ataxia-telangiectasia (AT)
      variant, is an autosomal recessive disorder characterized by microcephaly, growth
      retardation, severe combined immunodeficiency and a high incidence of lymphoid
      cancers. Cells from NBS patients display chromosome instability, hypersensitivity
      to ionizing radiation and abnormal cell-cycle regulation after irradiation, all
      of which are characteristics shared with AT. Recently, the NBS locus was mapped
      at 8q21 by two independent approaches, complementation studies and linkage
      analysis. Here, we report the positional cloning of the NBS gene, NBS1, from an
      800-kb candidate region. The gene comprises 50 kb and encodes a protein of 754
      amino acids. The amino-terminal region of the protein shows weak homology to the
      yeast XRS2, MEK1, CDS1 and SPK1 proteins. The gene is expressed at high levels in
      the testes, suggesting that it might be involved in meiotic recombination. We
      detected the same 5-bp deletion in 13 individuals, and conclude that it is likely
      to be a founder mutation.

PMID- 9620778
TI  - Expression of TERT in early premalignant lesions and a subset of cells in normal
      tissues.
AB  - Activation of telomerase, the enzyme that synthesizes the telomere ends of linear
      chromosomes, has been implicated in human cell immortalization and cancer cell
      pathogenesis. Enzyme activity is undetectable in most normal cells and tissues,
      but present in immortal cells and cancer tissues. While expression of TERC, the
      RNA component of telomerase, is widespread, the restricted expression pattern of
      TERT, the telomerase catalytic subunit gene, is correlated with telomerase
      activity, and its ectopic expression in telomerase-negative cells is sufficient
      to reconstitute telomerase activity and extend cellular lifespan. We have used in
      situ hybridization to study TERT expression at the single-cell level in normal
      tissues and in various stages of tumour progression. In normal tissues, including
      some that are known to be telomerase-negative, TERT mRNA was present in specific
      subsets of cells thought to have long-term proliferative capacity. This included
      mitotically inactive breast lobular epithelium in addition to some actively
      regenerating cells such as the stratum basale of the skin. TERT expression
      appeared early during tumorigenesis in vivo, beginning with early pre-invasive
      changes in human breast and colon tissues and increasing gradually during
      progression, both in the amount of TERT mRNA present within individual cells and
      in the number of expressing cells within a neoplastic lesion. The physiological
      expression of TERT within normal epithelial cells that retain proliferative
      potential and its presence at the earliest stages of tumorigenesis have
      implications for the regulation of telomerase expression and for the
      identification of cells that may be targets for malignant transformation.

PMID- 9620779
TI  - Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription.
AB  - CpG methylation in vertebrates correlates with alterations in chromatin structure
      and gene silencing. Differences in DNA-methylation status are associated with
      imprinting phenomena and carcinogenesis. In Xenopus laevis oocytes, DNA
      methylation dominantly silences transcription through the assembly of a
      repressive nucleosomal array. Methylated DNA assembled into chromatin binds the
      transcriptional repressor MeCP2 which cofractionates with Sin3 and histone
      deacetylase. Silencing conferred by MeCP2 and methylated DNA can be relieved by
      inhibition of histone deacetylase, facilitating the remodelling of chromatin and
      transcriptional activation. These results establish a direct causal relationship
      between DNA methylation-dependent transcriptional silencing and the modification
      of chromatin.

PMID- 9620780
TI  - The chromo and SET domains of the Clr4 protein are essential for silencing in
      fission yeast.
AB  - Heritable inactivation of specific regions of the genome is a widespread,
      possibly universal phenomenon for gene regulation in eukaryotes. Self
      perpetuating, clonally inherited chromatin structure has been proposed as the
      explanation for such phenomena as position-effect variegation (PEV) and control
      of segment determination and differentiation in flies, X-chromosome inactivation
      and parental imprinting in mammals, gene silencing by paramutation in maize and
      silencing of the mating-type loci in yeasts. We have now found that the clr4
      gene, which is essential for silencing of centromeres and the mating-type loci in
      Schizosaccharomyces pombe, encodes a protein with high homology to the product of
      Su(var)3-9, a gene affecting PEV in Drosophila. Like Su(var)3-9p, Clr4p contains
      SET and chromo domains, motifs found in proteins that modulate chromatin
      structure. Site-directed mutations in the conserved residues of the chromo domain
      confirm that it is required for proper silencing and directional switching of the
      mating type, like SET domain. Surprisingly, RNA differential display experiments
      demonstrated that clr4+ can mediate transcriptional activation of certain other
      loci. These results show that clr4 plays a critical role in silencing at mating
      type loci and centromeres through the organization of repressive chromatin
      structure and demonstrate a new, activator function for Clr4p.

PMID- 9620781
TI  - Genetic mapping of a second myotonic dystrophy locus.
AB  - We report the mapping of a second myotonic dystrophy locus, myotonic dystrophy
      type 2 (DM2). Myotonic dystrophy (DM) is a multi-system disease and the most
      common form of muscular dystrophy in adults. In 1992, DM was shown to be caused
      by an expanded CTG repeat in the 3' untranslated region of the dystrophia
      myotonica-protein kinase gene (DMPK) on chromosome 19 (refs 2-6). Although
      several theories have been put forth to explain how the CTG expansion causes the
      broad spectrum of clinical features associated with DM, it is not understood how
      this mutation, which does not alter the protein-coding region of a gene, causes
      an affect at the cellular level. We have identified a five-generation family
      (MN1) with a genetically distinct form of myotonic dystrophy. Affected members
      exhibit remarkable clinical similarity to DM (myotonia, proximal and distal limb
      weakness, frontal balding, cataracts and cardiac arrhythmias) but do not have the
      chromosome-19 D CTG expansion. We have mapped the disease locus (DM2) of the MN1
      family to a 10-cM region of chromosome 3q. Understanding the common molecular
      features of two different forms of the disease should shed light on the
      mechanisms responsible for the broad constellation of seemingly unrelated
      clinical features present in both diseases.

PMID- 9620782
TI  - Telomere elongation by hnRNP A1 and a derivative that interacts with telomeric
      repeats and telomerase.
AB  - Telomeric DNA of mammalian chromosomes consists of several kilobase-pairs of
      tandemly repeated sequences with a terminal 3' overhang in single-stranded form.
      Maintaining the integrity of these repeats is essential for cell survival;
      telomere attrition is associated with chromosome instability and cell senescence,
      whereas stabilization of telomere length correlates with the immortalization of
      somatic cells. Telomere elongation is carried out by telomerase, an RNA-dependent
      DNA polymerase which adds single-stranded TAGGGT repeats to the 3' ends of
      chromosomes. While proteins that associate with single-stranded telomeric repeats
      can influence tract lengths in yeast, equivalent factors have not yet been
      identified in vertebrates. Here, it is shown that the heterogeneous nuclear
      ribonucleoprotein A1 participates in telomere biogenesis. A mouse cell line
      deficient in A1 expression harbours telomeres that are shorter than those of a
      related cell line expressing normal levels of A1. Restoring A1 expression in A1
      deficient cells increases telomere length. Telomere elongation is also observed
      upon introduction of exogenous UP1, the amino-terminal fragment of A1. While both
      A1 and UP1 bind to vertebrate single-stranded telomeric repeats directly and with
      specificity in vitro, only UP1 can recover telomerase activity from a cell
      lysate. These findings establish A1/UP1 as the first single-stranded DNA binding
      protein involved in mammalian telomere biogenesis and suggest possible mechanisms
      by which UP1 may modulate telomere length.

PMID- 9620783
TI  - Severe growth defect in mouse cells lacking the telomerase RNA component.
AB  - The ribonucleoprotein enzyme telomerase synthesizes telomeric DNA onto chromosome
      ends. Telomere length is maintained, by the presence of telomerase activity, in
      the vast majority of primary tumours and stem cells, suggesting that telomere
      maintenance is essential for cellular immortalization. Recently, the telomerase
      RNA component in human and mouse (TERC and Terc, respectively), a telomerase
      associated protein TEP1/TLP1 (refs 6,7) and the human catalytic subunit protein
      TERT (refs 8,9) have been identified. To examine the role of telomerase in
      telomere maintenance and cellular viability, we established Terc-deficient
      embryonic stem (ES) cells. It is known that telomerase activity is absent in
      cells from Terc-knockout mice. Although the study showed that telomere shortening
      was observed in the Terc-deficient cells from first to six generation animals,
      whether telomerase-dependent telomere maintenance was essential for cellular
      viability remained to be elucidated. To address this issue, we examined Terc
      deficient ES cells under long-term culture conditions. Accompanying the continual
      telomere shortening, the growth rate of Terc-deficient ES cells was gradually
      reduced after more than 300 divisions. An impaired growth rate was maintained to
      approximately 450 divisions, and then cell growth virtually stopped. These data
      clearly show that telomerase-dependent telomere maintenance is critical for the
      growth of mammalian cells.

PMID- 9620784
TI  - Caveat investor.

PMID- 9620785
TI  - Entry standards to UK science courses fall.

PMID- 9620786
TI  - Drosophila set for fast-track sequencing.

PMID- 9620787
TI  - Venter backs call for more public funds.

PMID- 9620788
TI  - Bid to limit prices on drugs using 'public' discoveries.

PMID- 9620789
TI  - Chief to leave troubled British biotech.

PMID- 9620790
TI  - Germans mix support and scepticism for genetic engineering.

PMID- 9620791
TI  - Bioprospecting for drugs.

PMID- 9620792
TI  - Notch signalling. A short cut to the nucleus.

PMID- 9620793
TI  - The stress of Gulf War syndrome.

PMID- 9620794
TI  - Gene silencing. Methylation meets acetylation.

PMID- 9620795
TI  - Max's modelling.

PMID- 9620796
TI  - Connexin 26 gene linked to a dominant deafness.

PMID- 9620797
TI  - RAMPs regulate the transport and ligand specificity of the calcitonin-receptor
      like receptor.
AB  - Calcitonin-gene-related peptide (CGRP) and adrenomedullin are related peptides
      with distinct pharmacological profiles. Here we show that a receptor with seven
      transmembrane domains, the calcitonin-receptor-like receptor (CRLR), can function
      as either a CGRP receptor or an adrenomedullin receptor, depending on which
      members of a new family of single-transmembrane-domain proteins, which we have
      called receptor-activity-modifying proteins or RAMPs, are expressed. RAMPs are
      required to transport CRLR to the plasma membrane. RAMP1 presents the receptor at
      the cell surface as a mature glycoprotein and a CGRP receptor. RAMP2-transported
      receptors are core-glycosylated and are adrenomedullin receptors.

PMID- 9620798
TI  - Reflected infrared spectrum of a massive protostar in Orion.
AB  - The infrared source IRc2 in the star-forming region Orion-KL is generally
      believed to contain a massive and very young star. Its nature and evolutionary
      status, however, are difficult to determine because it is hidden from direct view
      by a dense disklike envelope of gas and dust. Here we report observations of
      infrared radiation (at a wavelength of about 2 microm) that has escaped the
      surrounding dust in the polar direction, perpendicular to the plane of the disk,
      and then been reflected towards us by dust farther away from the star. The
      reflected spectrum contains absorption lines of neutral metallic atoms and carbon
      monoxide, which we interpret as indicating a source temperature of about 4,500 K.
      But, given the luminosity of the source, its radius must be at least 300 solar
      radii-too large to be attained with the modest gas-accretion rates in existing
      theories of massive-star formation. Whether the infrared radiation is coming from
      the protostar itself or the self-luminous accretion disk around it, the accretion
      rate must be around (5-15) x 10(-3) solar masses per year, at least two orders of
      magnitude greater than is commonly assumed in models of star formation.

PMID- 9620799
TI  - The biosynthetic pathway of vitamin C in higher plants.
AB  - Vitamin C (L-ascorbic acid) has important antioxidant and metabolic functions in
      both plants and animals, but humans, and a few other animal species, have lost
      the capacity to synthesize it. Plant-derived ascorbate is thus the major source
      of vitamin C in the human diet. Although the biosynthetic pathway of L-ascorbic
      acid in animals is well understood, the plant pathway has remained unknown-one of
      the few primary plant metabolic pathways for which this is the case. L-ascorbate
      is abundant in plants (found at concentrations of 1-5 mM in leaves and 25 mM in
      chloroplasts) and may have roles in photosynthesis and transmembrane electron
      transport. We found that D-mannose and L-galactose are efficient precursors for
      ascorbate synthesis and are interconverted by GDP-D-mannose-3,5-epimerase. We
      have identified an enzyme in pea and Arabidopsis thaliana, L-galactose
      dehydrogenase, that catalyses oxidation of L-galactose to L-galactono-1,4
      lactone. We propose an ascorbate biosynthesis pathway involving GDP-D-mannose,
      GDP-L-galactose, L-galactose and L-galactono-1,4-lactone, and have synthesized
      ascorbate from GDP-D-mannose by way of these intermediates in vitro. The
      definition of this biosynthetic pathway should allow engineering of plants for
      increased ascorbate production, thus increasing their nutritional value and
      stress tolerance.

PMID- 9620800
TI  - Visual input evokes transient and strong shunting inhibition in visual cortical
      neurons.
AB  - The function and nature of inhibition of neurons in the visual cortex have been
      the focus of both experimental and theoretical investigations. There are two ways
      in which inhibition can suppress synaptic excitation. In hyperpolarizing
      inhibition, negative and positive currents sum linearly to produce a net change
      in membrane potential. In contrast, shunting inhibition acts nonlinearly by
      causing an increase in membrane conductance; this divides the amplitude of the
      excitatory response. Visually evoked changes in membrane conductance have been
      reported to be nonsignificant or weak, supporting the hyperpolarization mode of
      inhibition. Here we present a new approach to studying inhibition that is based
      on in vivo whole-cell voltage clamping. This technique allows the continuous
      measurement of conductance dynamics during visual activation. We show, in neurons
      of cat primary visual cortex, that the response to optimally orientated flashed
      bars can increase the somatic input conductance to more than three times that of
      the resting state. The short latency of the visually evoked peak of conductance,
      and its apparent reversal potential suggest a dominant contribution from gamma
      aminobutyric acid ((GABA)A) receptor-mediated synapses. We propose that nonlinear
      shunting inhibition may act during the initial stage of visual cortical
      processing, setting the balance between opponent 'On' and 'Off' responses in
      different locations of the visual receptive field.

PMID- 9620801
TI  - Acute stress facilitates long-lasting changes in cholinergic gene expression.
AB  - Acute traumatic stress may lead to post-traumatic stress disorder (PTSD), which
      is characterized by delayed neuropsychiatric symptoms including depression,
      irritability, and impaired cognitive performance. Curiously, inhibitors of the
      acetylcholine-hydrolysing enzyme acetylcholinesterase may induce
      psychopathologies that are reminiscent of PTSD. It is unknown how a single
      stressful event mediates long-term neuronal plasticity. Moreover, no mechanism
      has been proposed to explain the convergent neuropsychological outcomes of stress
      and of acetylcholinesterase inhibition. However, acute stress elicits a transient
      increase in the amounts released of the neurotransmitter acetylcholine and a
      phase of enhanced neuronal excitability. Inhibitors of acetylcholinesterase also
      promote enhanced electrical brain activity, presumably by increasing the survival
      of acetylcholine at the synapse. Here we report that there is similar
      bidirectional modulation of genes that regulate acetylcholine availability after
      stress and blockade of acetylcholinesterase. These calcium-dependent changes in
      gene expression coincide with phases of rapid enhancement and delayed depression
      of neuronal excitability. Both of these phases are mediated by muscarinic
      acetylcholine receptors. Our results suggest a model in which robust cholinergic
      stimulation triggers rapid induction of the gene encoding the transcription
      factor c-Fos. This protein then mediates selective regulatory effects on the long
      lasting activities of genes involved in acetylcholine metabolism.

PMID- 9620802
TI  - Increased NMDA current and spine density in mice lacking the NMDA receptor
      subunit NR3A.
AB  - The NMDA (N-methyl-D-aspartate) subclass of glutamate receptor is essential for
      the synaptic plasticity thought to underlie learning and memory and for synaptic
      refinement during development. It is currently believed that the NMDA receptor
      (NMDAR) is a heteromultimeric channel comprising the ubiquitous NR1 subunit and
      at least one regionally localized NR2 subunit. Here we report the
      characterization of a regulatory NMDAR subunit, NR3A (formerly termed NMDAR-L or
      chi-1), which is expressed primarily during brain development. NR3A co
      immunoprecipitates with receptor subunits NR1 and NR2 in cerebrocortical
      extracts. In single-channel recordings from Xenopus oocytes, addition of NR3A to
      NR1 and NR2 leads to the appearance of a smaller unitary conductance. Genetic
      knockout of NR3A in mice results in enhanced NMDA responses and increased
      dendritic spines in early postnatal cerebrocortical neurons. These data suggest
      that NR3A is involved in the development of synaptic elements by modulating NMDAR
      activity.

PMID- 9620803
TI  - Notch-1 signalling requires ligand-induced proteolytic release of intracellular
      domain.
AB  - Notch proteins are ligand-activated transmembrane receptors involved in cell-fate
      selection throughout development. No known enzymatic activity is contained within
      Notch and the molecular mechanism by which it transduces signals across the cell
      membrane is poorly understood. In many instances, Notch activation results in
      transcriptional changes in the nucleus through an association with members of the
      CSL family of DNA-binding proteins (where CSL stands for CBF1, Su(H), Lag-1). As
      Notch is located in the plasma membrane and CSL is a nuclear protein, two models
      have been proposed to explain how they interact. The first suggests that the two
      interact transiently at the membrane. The second postulates that Notch is cleaved
      by a protease, enabling the cleaved fragment to enter the nucleus. Here we show
      that signalling by a constitutively active membrane-bound Notch-1 protein
      requires the proteolytic release of the Notch intracellular domain (NICD), which
      interacts preferentially with CSL. Very small amounts of NICD are active,
      explaining why it is hard to detect in the nucleus in vivo. We also show that it
      is ligand binding that induces release of NICD.

PMID- 9620804
TI  - Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a
      histone deacetylase complex.
AB  - Cytosine residues in the sequence 5'CpG (cytosine-guanine) are often
      postsynthetically methylated in animal genomes. CpG methylation is involved in
      long-term silencing of certain genes during mammalian development and in
      repression of viral genomes. The methyl-CpG-binding proteins MeCP1 and MeCP2
      interact specifically with methylated DNA and mediate transcriptional repression.
      Here we study the mechanism of repression by MeCP2, an abundant nuclear protein
      that is essential for mouse embryogenesis. MeCP2 binds tightly to chromosomes in
      a methylation-dependent manner. It contains a transcriptional-repression domain
      (TRD) that can function at a distance in vitro and in vivo. We show that a region
      of MeCP2 that localizes with the TRD associates with a corepressor complex
      containing the transcriptional repressor mSin3A and histone deacetylases.
      Transcriptional repression in vivo is relieved by the deacetylase inhibitor
      trichostatin A, indicating that deacetylation of histones (and/or of other
      proteins) is an essential component of this repression mechanism. The data
      suggest that two global mechanisms of gene regulation, DNA methylation and
      histone deacetylation, can be linked by MeCP2.

PMID- 9620805
TI  - Transcriptional activation independent of TFIIH kinase and the RNA polymerase II
      mediator in vivo.
AB  - The carboxy-terminal domain (CTD) of the largest subunit of RNA polymerase II
      becomes multiply phosphorylated by protein kinases during early steps in the gene
      transcription cycle both in vivo and in vitro. In yeast, the major CTD kinase is
      a subunit of the general transcription factor TFIIH, and is encoded by an
      essential gene, KIN28. Although the CTD and its phosphorylation are important for
      transcription, in vitro studies have challenged whether CTD phosphorylation is an
      absolutely required step. The general importance of CTD phosphorylation by Kin28
      for transcription in yeast has been suggested because, for all genes tested,
      transcription is inhibited at the non-permissive temperature in temperature
      sensitive kin28 mutants. However, using such a mutant and a copper-inducible
      targeted destruction method, we show here that transcription of certain genes can
      be highly induced even when cells lack Kin28. We also show that transcription of
      these Kin28-independent genes is independent of Srb4 and Srb6, critical
      components of the CTD-associated transcriptional mediator complex. These results
      indicate that there are at least two distinct pathways for transcriptional
      activation: one is dependent on Kin28 and the mediator complex, and the other is
      not.

PMID- 9620806
TI  - Atomic structure of progesterone complexed with its receptor.
AB  - The physiological effects of progestins are mediated by the progesterone
      receptor, a member of the steroid/nuclear receptor superfamily. As progesterone
      is required for maintenance of pregnancy, its receptor has been a target for
      pharmaceuticals. Here we report the 1.8 A crystal structure of a progesterone
      bound ligand-binding domain of the human progesterone receptor. The nature of
      this structure explains the receptor's selective affinity for progestins and
      establishes a common mode of recognition of 3-oxy steroids by the cognate
      receptors. Although the overall fold of the progesterone receptor is similar to
      that found in related receptors, the progesterone receptor has a quite different
      mode of dimerization. A hormone-induced stabilization of the carboxy-terminal
      secondary structure of the ligand-binding domain of the progesterone receptor
      accounts for the stereochemistry of this distinctive dimer, explains the
      receptor's characteristic pattern of ligand-dependent protease resistance and its
      loss of repression, and indicates how the anti-progestin RU486 might work in
      birth control. The structure also indicates that the analogous 3-keto-steroid
      receptors may have a similar mechanism of action.

PMID- 9620807
TI  - Intention-to-treat vs. on-treatment analyses of clinical trial data: experience
      from a study of pyrimethamine in the primary prophylaxis of toxoplasmosis in HIV
      infected patients. ANRS 005/ACTG 154 Trial Group.
AB  - Randomized clinical trials analyzed by the intent-to-treat approach provide
      unbiased comparisons among treatment groups. To avoid dilution of treatment
      effect, many people also perform an analysis by treatment actually received,
      although this method may introduce bias into the results. This paper presents
      several approaches used for analyzing data of a recent trial and the difficulties
      encountered in interpreting the results of each approach. The ANRS 005/ACTG 154
      Study was a double-blind, placebo-controlled, randomized, international (French,
      U.S., and Spanish) multicenter trial designed to assess the effectiveness of
      pyrimethamine for the primary prophylaxis of cerebral toxoplasmosis (CT) in HIV
      infected patients with advanced immunodeficiency. In the intention-to-treat
      analysis, the cumulative probability of CT at 1 year did not differ significantly
      between the pyrimethamine arm (11.9%) and the placebo arm (13.1%), Hazard Ratio
      (HR) = 0.94 (95% Confidence Interval (CI) = 0.62-1.42), whereas an on-treatment
      analysis resulted in a significant difference: 4.2% in the pyrimethamine arm and
      12.4% in the placebo arm, HR = 0.44 (95% CI = 0.24-0.80). The data showed a
      significant interaction between compliance and treatment outcome; and side
      effects were more frequently cited as reasons for compliance violations in the
      pyrimethamine group. Several different analytic approaches (censoring data at the
      time patients discontinued the study medication only for selected reasons) failed
      to explain the disparity between the estimation of effect of pyrimethamine by the
      intention-to-treat and on-treatment analyses. This experience led us to believe
      that comparing the results of both analyses was the best method to convince
      clinicians that intention-to-treat was the only interpretable analysis. We were
      concerned that even if pyrimethamine had a beneficial effect, it was very
      difficult (1) to quantify and (2) to apply to clinical practice unless one could
      predict the occurrence of study drug discontinuation for each patient at the time
      of treatment assignment. Although exploratory analyses may yield clinically
      relevant information and useful clarifications in the evaluation of treatments,
      intention-to-treat remains the only interpretable analysis of clinical trials.

PMID- 9620808
TI  - Should we adjust for covariates in nonlinear regression analyses of randomized
      trials?
AB  - The analyses of the primary objectives of randomized clinical trials often are
      not adjusted for covariates, except possibly for stratification variables. For
      analyses with linear models, adjustment is a precision issue only. We review the
      literature regarding logistic and Cox (proportional hazards) regression models.
      For these nonlinear analyses, omitting covariates from the analysis of randomized
      trials leads to a loss of efficiency as well as a change in the treatment effect
      being estimated. We recommend that the primary analyses adjust for important
      prognostic covariates in order to come as close as possible to the clinically
      most relevant subject-specific measure of treatment effect. Additional benefits
      would be an increase in efficiency of tests for no treatment effect and improved
      external validity. The latter is particularly relevant to meta-analyses.

PMID- 9620809
TI  - Drug compliance in therapeutic trials: a review.
AB  - Because poor compliance introduces a major risk of bias in the interpretation of
      the results of a therapeutic trial, it is an important element to consider. At
      the planning stage, factors known to be associated with poor compliance should be
      recognized. The different methods of evaluating compliance, either clinical or
      biological, should be reviewed and the best strategy selected. During the
      therapeutic trial, the objective is to maintain an appropriate level of
      compliance. Patients, investigators, and sponsors have different options and
      responsibilities. The analysis should incorporate compliance as a specific
      variable in order to help test the robustness of the data. Compliance constitutes
      by itself a specific outcome measure. Compliance should be an integral part of
      study reports and publications, but it is frequently not discussed.

PMID- 9620810
TI  - Publishing clinical trials and dealing with external comparisons.
AB  - This brief note is designed to provide research teams that are involved with the
      publication of clinical trials in peer-reviewed medical journals with a reference
      for the rebuttal of referees' criticism that your results are in some way
      inferior overall to those of others. In these reviewers' eyes, a trial that shows
      less benefit than other trials has no public health benefit, and hence they
      recommend rejection. In fact, such policies lead to publication bias, the
      systematic overestimation of benefits of therapy in the published literature.

PMID- 9620811
TI  - The ischemic optic neuropathy decompression trial (IONDT): design and methods.
AB  - The objective of the Ischemic Optic Neuropathy Decompression Trial (IONDT) was to
      investigate the safety and efficacy of optic nerve decompression surgery (ONDS)
      compared to careful follow-up for nonarteritic ischemic optic neuropathy (NAION)
      and to observe the natural history of NAION in untreated patients. It was
      designed as a multicenter, randomized controlled clinical trial. Resource centers
      included a Chairman's Office, a Coordinating Center, and 25 Clinical Centers at
      eye centers throughout the United States. The trial's methods were as follows.
      Eligible patients with visual acuity 20/64 or worse were randomized to ONDS or
      careful follow-up; eligible patients with visual acuity better than 20/64 made up
      a natural history cohort and were followed but not randomized to treatment. The
      primary outcome examined was an increase of three lines or more of visual acuity
      at 6 months. Additional outcomes were visual acuity at other follow-up times,
      visual field, quality of life, and morbidity associated with ONDS. Standard
      quality assurance methodology was used to monitor adherence to protocol. The
      surgical protocol was monitored by a Surgical Quality Assurance Committee (SQAC).
      Enrollment began October 8, 1992, and ceased October 20, 1994, because of
      preliminary findings indicating that surgery was of no benefit and was perhaps
      harmful. This report describes the design and methods of the trial and the
      rationale for design elements unique to the IONDT. Specific goals of study design
      and conduct included achieving an accelerated study start-up and rapidly
      producing results acceptable to the medical community.

PMID- 9620812
TI  - A methodology report of a randomized prospective clinical trial to assess
      velopharyngeal function for speech following palatal surgery.
AB  - Cleft lip and palate occurs in approximately 1 in every 750 live human births,
      making it one of the most common congenital malformations. Surgical closure of
      the palatal cleft does not always result in a velopharyngeal port capable of
      supporting normal speech. The University of Florida (UF), in collaboration with
      the University of Sao Paulo (USP), is engaging in a 5-year prospective,
      randomized controlled study to compare velopharyngeal function for speech
      outcomes between patients undergoing palatoplasty for complete unilateral cleft
      lip and palate performed using the von Langenbeck procedure with intravelar
      velarplasty and those receiving the Furlow double-reversing Z-plasty
      palatoplasty. The von Langenbeck procedure was selected as the time-tested
      standard against which the Furlow procedure could be judged. The Furlow
      procedure, a relatively new operation, has been reported to yield substantially
      higher rates of velopharyngeal competency for speech than have most other
      reported series and theoretically should result in less disturbance to midfacial
      growth. A total of 608 patients will be entered into one of two age categories.
      Inclusion of two age groups will allow a comparison of results between patients
      having surgery before 1 year of age (9-12 months) and patients undergoing surgery
      at approximately 1.5 years of age (15-18 months). Speech data will be collected
      and will be available for definitive analysis throughout the last 3 years of the
      study. Collection of preliminary growth data will require more than 5 years;
      growth analysis is anticipated to continue until all patients have reached
      maturity. The Hospital for Research and Rehabilitation of Patients with Cleft Lip
      and Palate at the University of Sao Paulo (USP-HPRLLP) in Bauru, Brazil, is
      uniquely situated for conducting this study. The well-equipped and modern
      facilities are staffed by well-trained specialists representing all disciplines
      in cleft-palate management. In addition, an already existing social services
      network throughout Brazil will ensure excellent follow-up of study cases. The
      clinical caseload at this institution currently exceeds 22,000, and more than
      1200 new cases are added annually. This project represents a unique opportunity
      to obtain prospective data from a large number of subjects while controlling the
      variables that have traditionally plagued cleft-palate studies. This study is
      designed to determine which of the two proposed surgical procedures is superior
      in constructing a velum capable of affecting velopharyngeal competency for the
      development of normal speech.

PMID- 9620813
TI  - Multifetal reduction: in search of Solomon.

PMID- 9620814
TI  - Breastfeeding assessment tools.

PMID- 9620815
TI  - A review of women and tobacco: have we come such a long way?
AB  - The trends in smoking by women over the past century parallel social and economic
      changes. The crumbling of the double standard spurred the tobacco industry to
      launch advertising campaigns that target women, juxtaposing images of liberation
      and feminism with glamour and slimness. As a result, in the 1990s, smoking
      initiation and prevalence is higher among teenage females than males. Tobacco
      related mortality and morbidity among women and their children continue to rise.
      Women's health care providers must be integral players in a multitiered, broad
      based approach to decreasing tobacco use among women. Research is needed on
      socially isolated women and on the efficacy of nursing interventions related to
      tobacco use.

PMID- 9620816
TI  - Gynecological care for women with mental retardation.
AB  - Gynecologic care of women with mental retardation often is overlooked because of
      the physical and ethical difficulties involved in providing such care. Nurse
      practitioners can use their assessment skills to understand these women better
      and provide safe care for them. Fertility and hygiene problems can be helped with
      medroxyprogesterone or low-dose contraceptives. Examinations can be accomplished
      by using a combination of desensitization classes and sedatives. Clinicians using
      such a protocol have been able to examine mentally retarded residents at
      Tacachale (a community for developmentally disabled people in Florida) without
      the use of general anesthesia.

PMID- 9620817
TI  - Intrapartal tocolysis: an option for acute intrapartal fetal crisis.
AB  - Tocolytic drugs are commonly used by the obstetric community to produce uterine
      quiescence in premature labor. The use of tocolytic agents has been expanded to
      intrapartal emergencies. Intrapartal tocolysis has implications for obstetric
      nurses, which include possession of knowledge of the pharmacologic and
      physiologic effects of these drugs. Intrapartal tocolysis offers a beneficial
      management strategy that can be used in an acute intrapartal fetal crisis. The
      use of tocolytics provides valuable time for the health care team to assess the
      etiology of a nonreassuring fetal heart rate pattern, increase options for the
      birth, and mobilize resources for delivery.

PMID- 9620818
TI  - Improving interactions between substance abusing mothers and their substance
      exposed newborns.
AB  - OBJECTIVE: To determine whether teaching comforting and interacting techniques
      within 24 hours of delivery to substance-abusing mothers will improve mother
      infant interactions 48-72 hours after discharge. DESIGN: An experimental three
      group, random assignment, pretest-posttest design. SETTING: Mothers attending a
      clinic serving a mostly indigent population. PARTICIPANTS: Eighty-three women
      whose urine was positive for drug use were invited to participate. Sixty mother
      newborn couplets completed the study. INTERVENTIONS: Two observers, blind to the
      mothers' drug history, completed the Nursing Child Assessment Feeding Scale
      (NCAFS) of all participants within 24 hours of delivery. Mothers in the
      experimental group were given the intervention. The observers completed the NCAFS
      in the mothers' homes 48-72 hours after discharge. RESULTS: At the home visit,
      couplets in the treatment group showed significant improvement in their total
      NCAFS score (F = 5.18; p = .008). When analyzed separately, only maternal scores
      showed a significant difference between the treatment and control groups at the
      home visit (F = 6.48; p = .0029). CONCLUSIONS: Nurses, by demonstrating
      caregiving behavior, can help mothers recognize and respond to newborns'
      behavioral cues, thus enhancing mother-newborn interactions.

PMID- 9620819
TI  - Reliability of length measurements in full-term neonates.
AB  - OBJECTIVE: To describe and compare the intra- and interexaminer reliability of
      four techniques for measuring length in full-term newborns and to determine
      whether the different techniques yield significantly different measurements.
      DESIGN: A descriptive study, describing the intra- and interexaminer reliability
      of four length measurement techniques: crown-heel, supine, paper barrier, and Neo
      infantometer. The nurses were blind to their own and to the other nurse's
      measurements. The order of the nurses and the order in which the measurements
      were obtained was randomized. SETTING: Mothers' rooms in a university hospital.
      PARTICIPANTS: Thirty-two healthy full-term newborns. INTERVENTIONS: Length
      measurements using four different length techniques were obtained twice each by
      two experienced neonatal nurses. MAIN OUTCOME MEASURES: To measure the intra- and
      interexaminer reliability, the following statistics were calculated: mean
      absolute differences, standard deviations, technical error of measurement;
      percentage less than .5 and 1.0 cm, and percentage of error. RESULTS: Intra- and
      interexaminer differences were significantly larger when examiners used the crown
      heel measurement technique. Although the intra- and interexaminer reliability of
      length measurements obtained with the supine, paper barrier, and Neo-infantometer
      techniques did not differ significantly, the amount of error in these
      measurements was large. CONCLUSIONS: Measurements obtained using the crown-heel
      technique are significantly less reliable than measurements obtained using the
      supine, paper barrier, or Neo-infantometer techniques.

PMID- 9620820
TI  - Predicting low-risk pregnant women's attendance at a preterm birth prevention
      class.
AB  - OBJECTIVE: To determine factors that predict attendance at a preterm birth
      prevention (PTBP) class in a sample of low-risk pregnant women. DESIGN:
      Predictive correlational. Discriminant function analysis with four predictor
      variables distinguished between women who did and did not attend a PTBP class.
      SETTING: A prenatal clinic in a large health maintenance organization.
      PARTICIPANTS: One hundred three pregnant women who were identified as being at
      low risk for preterm birth. MAIN OUTCOME MEASURES: Early in pregnancy,
      participants completed the Health Locus of Control scale, the Health Value Scale,
      the Perceived Barriers Scale, and a demographic questionnaire that included
      questions about prenatal education. Preterm birth prevention class attendance was
      determined by checking clients' electronic prenatal records at 26 weeks
      gestation. RESULTS: Women who attended the PTBP class had planned to attend
      pregnancy education classes, F(1, 98) = 5.18, p < .05, and perceived fewer
      barriers to class attendance, F(1, 98) = 13.53, p < .001, than did women who did
      not attend. CONCLUSIONS: Surveying clients to determine the most convenient times
      and locations and the availability of transportation can help nurses plan more
      accessible classes. Nurses should ascertain women's plans for attending pregnancy
      education classes and reinforce such plans.

PMID- 9620821
TI  - Giving birth: Guatemalan women's voices.
AB  - OBJECTIVE: To gain an understanding of the cultural meanings of giving birth for
      Guatemalan women. DESIGN: Ethnographic, focusing on the birth stories of
      Guatemalan women and their perceptions of the sociocultural context of
      childbearing. PARTICIPANTS AND SETTING: Thirty Guatemalan women (15 primiparae
      and 15 multiparae) of mixed Mayan and Ladino heritage who had given birth to
      healthy full-term infants were interviewed during the early postpartum weeks.
      These women lived in small villages in the Sacatepequez District of Guatemala.
      These audiotaped interviews were conducted in the Nacional Pedro de Bethancourt
      Hospital, in clinics, in the homes of the women, or in central plazas. RESULTS:
      The sociocultural context of giving birth in Guatemala is described, including
      common beliefs about pregnancy and childbirth and the meaning and significance of
      having children. The predominant themes found were the sacred nature of
      childbirth; the need for reliance on God during pregnancy, childbirth, and
      childrearing; and the bittersweet paradox of giving birth. CONCLUSION: With
      increasing numbers of Central American refugees and immigrants of childbearing
      age entering the United States, it is important for nurses to recognize,
      acknowledge, and respect specific cultural practices related to childbearing.

PMID- 9620822
TI  - The constipation assessment scale for pregnancy.
AB  - OBJECTIVE: To determine the reliability and validity of the Constipation
      Assessment Scale (CAS) during pregnancy. DESIGN: Survey. SETTING: The assessment
      tool was administered first to a group of healthy women of childbearing age in a
      school of nursing and then to pregnant women in their physicians' offices.
      PARTICIPANTS: A nonrandom sample of 16 nonpregnant women of childbearing age and
      30 women pregnant 28 weeks or longer, 15 of whom had low-risk pregnancies and 15
      of whom had high-risk pregnancies. MAIN OUTCOME MEASURES: The test-retest
      reliability, content validity, and internal consistency of the CAS were
      determined. RESULTS: An expert panel review found a calculated percentage of
      agreement for content validity of .75 and a Cohen's kappa of .714. Test-retest
      reliability based on 16 nursing students yielded high positive correlations
      ranging from rH = .84 to rH = .92. Internal consistency of the CAS for pregnancy
      based on the 30 surveys indicated an alpha coefficient of .82. CONCLUSIONS: The
      CAS for pregnancy was found to be reliable and valid within the context of this
      study. Future studies designed to identify potential therapeutic interventions
      for constipation during pregnancy could use the CAS for pregnancy as a
      measurement instrument.

PMID- 9620824
TI  - Fetal surveillance in multifetal pregnancy.
AB  - Multiple methods of tocolysis and fetal surveillance provide unprecedented ways
      to improve multifetal outcomes through meticulous antepartum care. Although few
      practitioners have much experience with these complicated pregnancies, knowledge
      is growing with the increasing incidence of multifetal pregnancy. A review of the
      current literature regarding antepartum surveillance provides the basis for a
      discussion of the techniques essential to quality nursing care during multifetal
      pregnancy. Guidelines are provided for nursing standards in documentation,
      terminology, and care during surveillance of multiple fetuses.

PMID- 9620823
TI  - The multiple birth explosion: implications for nursing practice.
AB  - An explosion in multiple birth rates has generated record numbers of multiple
      pregnancies and infants. Obstetric and neonatal nurses and those in related
      practice areas, such as reproductive endocrinology, perinatal education, home
      health, and lactation services, need special knowledge and resources to provide
      optimal care for these high-risk families. Multiple birth families have a number
      of unique health care problems that require directed nursing interventions
      throughout the perinatal continuum.

PMID- 9620825
TI  - A view from the other side of the bed.
AB  - A unique perspective on multiple pregnancy is shared through the writings of an
      expectant mother of triplets during the 19 weeks she spent on strict bed rest, 15
      of which were in the hospital. The expectant mother in this case is also a family
      physician, who finds herself on the opposite side of the patient bed to which she
      is accustomed. Through excerpts from her journal, the emotional ups and downs of
      a complicated pregnancy are revealed, along with the sources of strength and
      courage that kept her going. Commentary regarding the psychologic theory and
      developmental tasks of multiple pregnancy provide a foundation for suggesting
      effective nursing interventions for the psychosocial demands of these often high
      risk pregnancies.

PMID- 9620826
TI  - Depression and anxiety disorders during multiple pregnancy and parenthood.
AB  - Depression or anxiety disorders may affect more than 25% of multiple birth
      parents during the perinatal period. Such parents often are uninformed, suffer in
      silence and fear, and are reticent to seek help. When depression, panic attacks,
      and obsessive-compulsive disorder are not recognized or are left untreated,
      parent health, parent-infants interaction, child development, and family
      stability may be seriously compromised. Nurses, as partners in care at the family
      and community levels, have a pivotal role to play in prevention-focused health,
      education, and social support programs; the identification of parents at risk;
      and the early recognition and support of women and families affected by these
      disorders.

PMID- 9620827
TI  - Multifetal pregnancy reduction.
AB  - Higher-order multiple pregnancy is associated with significant maternal and fetal
      complications. Multifetal pregnancy reduction is one option for women with a
      higher-order multiple pregnancy. Various aspects of multifetal pregnancy
      reduction are discussed, including the background, options, risks, benefits,
      techniques, results, and appropriate physical and psychosocial support.

PMID- 9620829
TI  - Spermatozoa and antibodies.

PMID- 9620828
TI  - Sperm survival in the female reproductive tract: presence of immunosuppression or
      absence of recognition?

PMID- 9620830
TI  - Direct evidence for the involvement of carbohydrate sequences in human sperm-zona
      pellucida binding.
AB  - Several lines of evidence indicate that mammalian fertilization is initiated via
      a binding process that is dependent upon the recognition of oligosaccharide
      sequences associated with zona pellucida (ZP) glycoproteins. Here, specific
      chemical and enzymatic methods were employed to modify human ZP and to test their
      effects on sperm binding in the hemizona assay system (HZA). Periodate oxidation
      of human ZP under very mild conditions (10 min, 0 degrees C, 1 mM sodium m
      periodate) that attacks only terminal sialic acid resulted in a 30% loss of human
      sperm binding in the HZA [hemizona index (HZI) = 70.2 +/- 10.9, n = 22; P <
      0.05]. Periodate oxidation under mild conditions (1 h, 23 degrees C, 10 mM sodium
      m-periodate) caused a 40% decrease in binding (HZI = 60.8 +/- 10.3; n = 24; P<
      0.01). Treatment of human ZP with neuraminidase caused a substantial increase in
      sperm binding to human ZP (HZI = 297 +/- 45, n = 22; P < 0.01). These findings
      indicate that there are sialic acid dependent binding sites coexisting with
      binding sites that are obscured by sialic acid. To determine the periodate
      sensitivity of these obscured sites, hemizona were first digested with
      neuraminidase and subsequently subjected to mild periodate oxidation. The
      combined enzymatic and chemical treatments caused a 79% decrease in sperm binding
      compared to control hemizona (HZI = 20.7 +/- 4.4, n = 16; P < 0.001). Human sperm
      ZP interaction was also increased by digestion of human ZP with endo-beta
      galactosidase (HZI = 710 +/- 232, n = 14; P < 0.01), indicating that potential
      binding sites for spermatozoa are also obscured by lactosaminoglycan sequences.
      These studies support a definitive role for the involvement of ZP-associated
      glycans in the binding of human spermatozoa to oocytes.

PMID- 9620831
TI  - Interstitial and terminal deletion of chromosome Y in a male individual with
      cryptozoospermia.
AB  - A constitutional de-novo deletion of the long arm of the Y chromosome was
      detected by standard cytogenetic analysis in a 38-year old male who, except for
      small testes and cryptozoospermia, was phenotypically normal. The deletion was
      further characterized by fluorescent in-situ hybridization (FISH) and digital
      image analysis using contigs of overlapping yeast artificial chromosome (YAC)
      clones, spanning almost the entire Y chromosome. These results showed that the
      deletion involved a large interstitial segment on the proximal long arm of the Y
      chromosome (Yq11.1-->Yq11.22) as well as a more distal portion of the Y
      chromosome, including the entire heterochromatic region (Yq11.23-->qter). The
      breakpoints as determined by the YAC probes were defined within the published
      Vergnaud intervals so that region 6B and 6C was mostly retained. However, the
      AZFc region harbouring the DAZ locus on distal subinterval 6F was lost in the
      deletion, making the absence of this region the most probable location for the
      patient's infertility. The data underline the usefulness of FISH as an
      alternative technique to conventional banding for the refined detection of
      chromosome Y deletions/rearrangements.

PMID- 9620832
TI  - Cystic fibrosis mutation screening in CBAVD patients and men with obstructive
      azoospermia or severe oligozoospermia.
AB  - Congenital bilateral absence of the vas deferens (CBAVD) found in otherwise
      healthy infertile males, is associated with a high incidence of mutated cystic
      fibrosis transmembrane conductance regulator (CFTR) alleles, and is considered a
      genital form of cystic fibrosis (CF). The CF gene may also be involved in the
      aetiology of male infertility in cases other than CBAVD. The present study was
      undertaken to test the involvement of CFTR gene mutations in 14 CBAVD males and
      additionally in cases of male infertility caused by obstructive azoospermia (n =
      10) and severe oligozoospermia (n = 3). The entire coding region of the CFTR gene
      was analysed using denaturing gradient gel electrophoresis (DGGE). The three
      allele (5T, 7T, 9T) polymorphic tract of thymidines in intron 8 (IVS8-polyT) of
      which the 5T allele acts as a mild mutation, causing reduced levels of normal
      CFTR mRNA due to deletion of exon 9, was also analysed. Of the 14 CBAVD cases,
      four (28.6%) were found to have mutations in both copies of the CFTR gene, six
      (42.8%) had one CFTR mutation, and in the remaining four (28.6%) no CFTR
      mutations were found. Of the 10 cases with obstructive azoospermia, three (30%)
      had one CFTR mutation and in the remaining seven (70%) no mutations were found.
      None of the three severe oligozoospermia cases carried a CFTR mutation. The
      frequency of the IVS8(5T) allele was 14.3% (4/28) for the CBAVD cases and 5%
      (1/20) for the obstructive azoospermia cases, none of the severe oligozoospermia
      males carried the IVS8-5(5T) allele. The data indicate that while there is a
      strong association between male infertility caused by CBAVD and mutations in the
      CFTR gene, cases of obstructive azoospermia without CBAVD also seem to be
      associated with CFTR gene mutations.

PMID- 9620833
TI  - Phorbol esters and synthetic diacylglycerols inhibit gamma-aminobutyric acid
      uptake in human spermatozoa: an effect mediated by protein kinase C?
AB  - Protein kinase C (PKC) and protein kinase A (PKA) are present in human
      spermatozoa and probably involved in the cascade systems leading to acrosomal
      exocytosis. We have investigated the possibility that these two protein kinases
      are involved in the regulation of gamma-aminobutyric acid (GABA) uptake in human
      spermatozoa. Swim-up preparations of human spermatozoa were exposed to phorbol 12
      myristate 13 acetate (PMA) and 1-oleoyl-2-acetyl-sn-glycerol (OAG), which are
      activators of PKC, and to dibutyryl cyclic AMP (dbcAMP), a PKA activator, and
      subsequently incubated with radiolabelled GABA. Accumulated intracellular GABA
      was measured in a scintillation counter. Both PMA and OAG caused inhibition of
      GABA uptake while dbcAMP was without effect. The inhibitory effect on GABA uptake
      observed following exposure to the PKC activators could, however, not be
      counteracted by preincubation of the sperm samples with the PKC inhibitors
      staurosporine or H-7. The inhibitory effect on GABA uptake following addition of
      PMA was enhanced by prolonged exposure to the reagent and by increased
      capacitation prior to addition of the reagent. A small numerical increase in the
      percentage of acrosome-reacted cells was observed following exposure of the sperm
      cells to the highest concentrations of PMA, OAG and dbcAMP. No sperm motility
      parameters were affected by the treatment protocols as measured using computer
      assisted semen analysis (CASA).

PMID- 9620834
TI  - Preimplantation diagnosis of non-deletion Duchenne muscular dystrophy (DMD) by
      linkage polymerase chain reaction analysis.
AB  - The use of preimplantation diagnosis for sex determination and detection of exon
      deletion means that unaffected babies can be born to parents suffering from
      Duchenne muscular dystrophy (DMD). However, those who do not have exon deletion
      should also be considered for further investigation. A new method, known as
      linkage analysis, has been developed to diagnose the presence of non-deletion DMD
      in preimplantation embryos. Linkage analysis uses informative intragenic and
      flanking markers to track the chromosome bearing the mutated gene. The present
      study reports the analysis of two polymorphic sites, in blastomeres biopsied from
      embryos from a female carrier of DMD. A single male embryo was obtained who had
      inherited alternate maternal alleles to the woman's affected surviving son, and
      this embryo was transferred.

PMID- 9620835
TI  - Preimplantation diagnosis of autosomal dominant retinitis pigmentosum using two
      simultaneous single cell assays for a point mutation in the rhodopsin gene.
AB  - A couple requested preimplantation genetic analysis for a dominant form of
      retinitis pigmentosum caused by a C-->A transversion in the rhodopsin gene. Since
      this point mutation does not alter a restriction endonuclease site we designed
      two separate analytical systems, one involving site-specific mutagenesis and the
      other involving allele-dependent length polymorphism. After establishing the
      accuracy and robustness of these assay systems we utilized both systems
      simultaneously in a heminested polymerase chain reaction (PCR) system. This
      allowed accurate preimplantation diagnosis to be performed. One embryo was
      transferred but a pregnancy did not occur.

PMID- 9620836
TI  - Platelet-endothelial cell adhesion molecule-1 is expressed by a subpopulation of
      human trophoblasts: a possible mechanism for trophoblast-endothelial interaction
      during haemochorial placentation.
AB  - The terminal event in the establishment of the haemochorial placenta in the human
      is the invasion of trophoblasts into the maternal vessels, a process in which
      trophoblasts interact directly with the vascular endothelium and degrade the
      vascular basement membrane and the tunica elastica of the vessels. To further
      understand this heterotypic cellular interaction, we investigated the expression
      by human trophoblasts of the vascular cell adhesion molecule platelet-endothelial
      cell adhesion molecule-1 (PECAM-1) as a possible mediator of the adhesive
      interaction between trophoblasts and endothelium. In vitro, human trophoblasts
      were found to express PECAM-1 mRNA and protein. Indirect immunofluorescence
      indicated a diffuse staining pattern, which was most intense in a subpopulation
      of trophoblast cells. Co-incubation of trophoblasts with endothelial cells showed
      interaction between these two cell types with strong expression of PECAM-1 at
      points of trophoblast-endothelial cell contact, suggesting that this cell
      adhesion molecule participates in this heterotypic cell interaction.
      Immunohistochemical localization of PECAM-1 in chorionic villi and first
      trimester implantation sites showed that, in vivo, only extravillous interstitial
      and endovascular trophoblasts were positive. In first trimester placentae,
      villous trophoblast and extravillous trophoblast in other locations than around
      or within the decidual vessels did not express this molecule. In term placentae,
      villous trophoblast did not express these adhesion molecules except for two
      specimens examined. This study demonstrates that PECAM-1 is expressed by a subset
      of human trophoblasts in vitro and in vivo. Its tissue localization suggests that
      PECAM-1 is important in mediating the adhesive interaction between trophoblasts
      and maternal vascular endothelium during the process of haemochorial
      placentation. Regulation of PECAM-1 expression by human trophoblasts may play a
      critical role in normal and abnormal vascular invasion during implantation and
      placentation.

PMID- 9620837
TI  - Production and secretion of thioredoxin from transformed human trophoblast cells.
AB  - Thioredoxin is a redox active protein which has been implicated in reproductive
      processes. In this study we investigated the intracellular production and
      extracellular secretion of placental thioredoxin by human cytotrophoblast cell
      lines which were used as in-vitro model systems. Results clearly demonstrated
      that thioredoxin is not only synthesized by these cells but is also secreted and
      that while the intracellular thioredoxin is present only as a 12 kDa form, it
      would appear that the extracellular thioredoxin is present in two forms, a
      predominant 12 kDa form accompanied by a lower amount of a 10 kDa form. The
      observed localization and possible secretion of thioredoxin at the feto-maternal
      interface suggest important roles for this protein during pregnancy.
      Intracellular thioredoxin may be involved in the prevention of cellular damage
      due to oxidative stress whereas extracellular thioredoxin may act to integrate
      the actions of the cytokine network operating at the feto-maternal interface
      thereby assisting with implantation and the successful establishment of
      pregnancy.

PMID- 9620838
TI  - Evidence for the existence of a novel pregnancy-associated soluble variant of the
      vascular endothelial growth factor receptor, Flt-1.
AB  - Angiogenesis is essential in physiological processes including ovulation,
      implantation and pregnancy. One of the most potent regulators is the cytokine
      vascular endothelial growth factor (VEGF). We provide evidence for a novel
      pregnancy-associated soluble variant of the VEGF receptor Flt-1. VEGF ranged from
      undetectable to 157.3 pg/ml (mean 49.9 pg/ml, SD 48.4 pg/ml) in plasma samples
      from normal volunteers (n = 10), but was undetectable in plasma from pregnant
      women (n = 12) and amniotic fluid (n = 10). Recoveries of spiked VEGF were poor
      in pregnancy-related samples, indicating the presence of VEGF-binding activity
      which was confirmed using biosensor and chromatographic techniques. Partial
      purification and protein sequencing indicated a novel soluble form of Flt-1 with
      a subunit size of 150 kDa. Normally present as a multimeric structure of
      approximately 400-550 kDa, complexes of 600-700 kDa were formed following binding
      of multiple VEGF molecules. Reverse transcriptase polymerase chain reaction of
      Flt-1 in placenta, amnion, chorion, human umbilical vein endothelial cells and
      cord blood samples produced bands of the predicted sizes but failed to identify
      any additional RNA species, and possible reasons for this are discussed. Soluble
      Flt-1 may be important in regulating the actions of VEGF in angiogenesis and
      trophoblast invasion and may have therapeutic implications in diseases with
      inappropriate angiogenesis such as proliferative retinopathies and cancer.

PMID- 9620839
TI  - Do alpha 2-adrenoceptors and imidazoline binding sites coexist in the human term
      placenta? Evidence from direct binding studies.
AB  - Alpha2-Adrenergic receptors and non-adrenergic imidazoline binding sites (IBS) in
      human placental membranes were investigated by means of the radioligands [3H]-RX
      821002 and [3H]-RX 781094 (idazoxan) respectively. Human term placentae (38-40
      weeks) were obtained immediately after vaginal delivery. The specific binding of
      the alpha2-subtype-selective [3H]-RX 821002 confirms the presence of alpha2
      adrenoceptors in the human placenta, while [3H]-idazoxan binds to non-adrenergic
      IBS. The sites were characterized by displacement analyses with various
      imidazoline and non-imidazoline drugs. The presence of an endogenous ligand for
      IBS has not yet been demonstrated. Clonidine displacing substance (CDS) was
      recently identified as agmatine; it recognizes both alpha2 and imidazoline
      receptors. This phenomenon was studied in crude placental membranes. The studies
      revealed that: (i) alpha2-adrenoceptors coexist with non-adrenergic IBS in human
      placental membranes; (ii) there is a strong probability that alpha2-adrenoceptors
      and IBS are pharmacologically distinct; and (iii) agmatine binds to placental
      alpha2 and imidazoline receptors with different affinities.

PMID- 9620840
TI  - Regulation of placental monocyte chemotactic and activating factor during
      pregnancy and chorioamnionitis.
AB  - A number of placental cytokines participate in the feto-maternal defence
      mechanism. Monocyte chemotactic and activating factor (MCAF) is one of these
      chemokines. We investigated the pattern of placental MCAF production, the
      localization of MCAF-producing cells in the placenta, and alterations in its
      expression in chorioamnionitis. The amounts of MCAF protein produced by the
      placenta increased during pregnancy irrespective of the presence of uterine
      contraction. MCAF mRNA was expressed at equivalent levels in the first and second
      trimester placenta, but at higher levels in the third trimester placenta.
      Chorioamnionitis in the third trimester placenta induced a 10-fold increase in
      MCAF protein production and a 3-fold increase in MCAF mRNA level.
      Immunohistochemical analysis of the placenta revealed the MCAF-producing cells to
      be trophoblasts. Stimulation of placental cells with lipopolysaccharide augmented
      MCAF production. These results indicate unique transcriptional and developmental
      regulation of MCAF mRNA and protein production during pregnancy and
      chorioamnionitis. Placental MCAF may be involved in the feto-maternal defence
      mechanism by activating feto-placental and maternal monocytes in
      chorioamnionitis.

PMID- 9620841
TI  - Effect of follicle stimulating hormone and insulin-like growth factors on
      proteolysis of insulin-like growth factor binding protein-4 in human granulosa
      cells.
AB  - Follicular fluid from dominant follicles, but not atretic follicles, contains
      insulin-like growth factor binding protein-4 (IGFBP-4) proteolytic activity. The
      effect of follicle stimulating hormone (FSH) and insulin-like growth factors
      (IGFs) on IGFBP-4 proteolytic activity was studied using granulosa cell cultures.
      Proteolytic activity was assessed by the incubation of [1251]-IGFBP-4 with medium
      and cleaved products which were analysed by autoradiography. The iodinated IGFBP
      4 was cleaved into an 18 kDa fragment when cells were incubated with FSH or IGFs
      while IGFBP-4 remained intact in the control culture. Inhibition of IGFBP-4
      degradation by several protease inhibitors suggests that IGFBP-4 degradation was
      induced by a metalloserine protease. The degradation of IGFBP-4 was not
      stimulated when cells were incubated with the IGF-I analogue, LR3-IGF-I, and
      insulin which binds to IGF-I receptor but has little or no affinity for IGFBPs.
      Addition of IGFs, but not FSH, to medium from untreated granulosa cell cultures
      stimulated proteolysis of [1251]-IGFBP-4. Similarly, exogenously added covalently
      cross-linked [125I]-IGF-II-IGFBP-4 complexes were proteolyzed; however, IGFs did
      not enhance the degradation of these complexes. These results suggest that human
      granulosa cells produce IGFBP-4 protease and that the increased susceptibility of
      IGFBP-4 to proteolysis is induced by the binding of IGFs to IGFBP-4. These novel
      mechanisms may be important in modulating IGF-mediated folliculogenesis in the
      ovary.

PMID- 9620842
TI  - Progesterone receptor subtype B is differentially regulated in human endometrial
      stroma.
AB  - Two anti-progesterone receptor (PgR) antibodies, a new one specific to PgRB, the
      other to PgR subtypes A + B, have been used to examine the cellular location of
      PgR subtypes A and B in normal endometrium throughout the menstrual cycle and in
      early human decidua by standard immunohistochemical techniques. PgR(A+B) is the
      receptor detected by the antibody recognizing both isoforms of the receptor. PgRB
      is the receptor detected by the new antibody specific to the B isoform. Since it
      is not possible to raise antibody specific to PgR subtype A, all
      immunohistochemical analysis of the PgRA subtype is by subtractive inference.
      Thus we refer to PgRA as the subtype responsible for positive immunoreactivity
      when the PgRB subtype cannot be specifically detected. Endometrial biopsies were
      collected from 40 women with regular menses (n = 5 each stage of cycle:
      menstrual; early, mid and late proliferative; ovulatory; early, mid, and late
      secretory). Decidual tissue was obtained from 10 women undergoing first trimester
      surgical termination of pregnancy. As previously reported, the PgR(A+B) antibody
      stained glandular and stromal nuclei during the proliferative phase but only
      stromal nuclei during the secretory phase and early pregnancy. The new PgRB
      antibody also stained both cell types intensely during the proliferative phase,
      but failed to stain either stromal or glandular nuclei strongly during the
      secretory phase and early pregnancy. We concluded that, while both PgR subtypes
      were present in glands and stroma in the proliferative phase, and both subtypes
      were dramatically reduced in the glands during the secretory phase, PgRA remained
      as the predominant type in the stroma during the secretory phase and early
      pregnancy. The profound effects of progesterone on endometrium during the
      secretory phase and early pregnancy appear to be mediated primarily by PgRA in
      the stroma.

PMID- 9620843
TI  - Compendium of animal rabies control, 1998. National Association of State Public
      Health Veterinarians, Inc.
AB  - The purpose of this Compendium is to provide information on rabies control to
      veterinarians, public health officials, and others concerned with rabies control.
      These recommendations serve as the basis for animal rabies-control programs
      throughout the United States and facilitate standardization of procedures among
      jurisdictions, thereby contributing to an effective national rabies-control
      program. This document is reviewed annually and revised as necessary.
      Recommendations for parenteral immunization procedures are contained in Part I;
      all animal rabies vaccines licensed by the United States Department of
      Agriculture (USDA) and marketed in the United States are listed in Part II; Part
      III details the principles of rabies control.

PMID- 9620844
TI  - Proteases to die for.

PMID- 9620845
TI  - The roles of FGFs in the early development of vertebrate limbs.

PMID- 9620846
TI  - Smad2 transduces common signals from receptor serine-threonine and tyrosine
      kinases.
AB  - SMAD proteins mediate signals from receptor serine-threonine kinases (RSKs) of
      the TGF-beta superfamily. We demonstrate here that HGF and EGF, which signal
      through RTKs, can also mediate SMAD-dependent reporter gene activation and induce
      rapid phosphorylation of endogenous SMAD proteins by kinase(s) downstream of
      MEK1. HGF induces phosphorylation and nuclear translocation of epitope-tagged
      Smad2 and a mutation that blocks TGF-beta signaling also blocks HGF signal
      transduction. Smad2 may thus act as a common positive effector of TGF-beta- and
      HGF-induced signals and serve to modulate cross talk between RTK and RSK
      signaling pathways.

PMID- 9620847
TI  - RNA-binding protein conserved in both microtubule- and microfilament-based RNA
      localization.
AB  - Vg1 mRNA translocation to the vegetal cortex of Xenopus oocytes requires intact
      microtubules, and a 3' UTR cis-acting element (termed VLE), which also mediates
      sequence-specific binding of several proteins. One protein, the 69-kD Vg1 RBP,
      associates Vg1 RNA to microtubules in vitro. Here we show that Vg1 RBP-binding
      sites correlate with vegetal localization. Purification and cloning of Vg1 RBP
      revealed five RNA-binding motifs: four KH and one RRM domains. Surprisingly, Vg1
      RBP is highly homologous to the zipcode binding protein implicated in the
      microfilament-mediated localization of beta actin mRNA in fibroblasts. These data
      support Vg1 RBP's direct role in vegetal localization and suggest the existence
      of a general, evolutionarily conserved mechanism for mRNA targeting.

PMID- 9620848
TI  - p107 is a suppressor of retinoblastoma development in pRb-deficient mice.
AB  - Hemizygosity for the retinoblastoma gene RB in man strongly predisposes to
      retinoblastoma. In the mouse, however, Rb hemizygosity leaves the retina normal,
      whereas in Rb-/- chimeras pRb-deficient retinoblasts undergo apoptosis. To test
      whether concomitant inactivation of the Rb-related gene p107 is required to
      unleash the oncogenic potential of pRb deficiency in the mouse retina, we
      inactivated both Rb and p107 by homologous recombination in embryonic stem cells
      and generated chimeric mice. Retinoblastomas were found in five out of seven
      adult pRb/p107-deficient chimeras. The retinal tumors showed amacrine cell
      differentiation, and therefore originated from cells committed to the inner but
      not the outer nuclear layer. Retinal lesions were already observed at embryonic
      day 17.5. At this stage, the primitive nuclear layer exhibited severe dysplasia,
      including rosette-like arrangements, and apoptosis. These findings provide formal
      proof for the role of loss of Rb in retinoblastoma development in the mouse and
      the first in vivo evidence that p107 can exert a tumor suppressor function.

PMID- 9620849
TI  - Targeted disruption of SHIP leads to hemopoietic perturbations, lung pathology,
      and a shortened life span.
AB  - SHIP is a 145-kD SH2-containing inositol-5-phosphatase widely expressed in
      hemopoietic cells. It was first identified as a tyrosine phosphoprotein
      associated with Shc in response to numerous cytokines. SHIP has been implicated
      in FcgammaRIIB receptor-mediated negative signaling in B cells and mast cells and
      is postulated to down-regulate cytokine signal transduction in myeloid cells. To
      define further its role in the proliferation and differentiation of hemopoietic
      progenitors, as well as its function in mature cells, we have generated embryonic
      stem cells and mice bearing a targeted disruption of both SHIP alleles. Here we
      show that although SHIP null mice are viable and fertile, they fail to thrive and
      survival is only 40% by 14 weeks of age. Mortality is associated with extensive
      consolidation of the lungs resulting from infiltration by myeloid cells.
      Increased numbers of granulocyte-macrophage progenitors are observed in both the
      bone marrow and spleen of SHIP-/- mice, perhaps as a consequence of hyper
      responsiveness to stimulation by macrophage-colony stimulating factor,
      granulocyte-macrophage colony stimulating factor, interleukin-3, or Steel factor
      as observed in vitro. In contrast, numbers of bone marrow lymphoid and late
      erythroid progenitors (CFU-E) are reduced. Thus, homozygous disruption of SHIP
      establishes the crucial role of this molecule in modulating cytokine signaling
      within the hemopoietic system and provides a powerful model for further
      delineating its function.

PMID- 9620850
TI  - The mammalian transcriptional repressor RBP (CBF1) targets TFIID and TFIIA to
      prevent activated transcription.
AB  - RBP is a cellular protein that functions as a transcriptional repressor in
      mammalian cells. RBP has elicited great interest lately because of its
      established roles in regulating gene expression, in Drosophila and mouse
      development, and as a component of the Notch signal transduction pathway. This
      report focuses on the mechanism by which RBP represses transcription and thereby
      regulates expression of a relatively simple, but natural, promoter. The results
      show that, irrespective of the close proximity between RBP and other
      transcription factors bound to the promoter, RBP does not occlude binding by
      these other transcription factors. Instead, RBP interacts with two
      transcriptional coactivators: dTAFII110, a subunit of TFIID, and TFIIA to repress
      transcription. The domain of dTAFII110 targeted by RBP is the same domain that
      interacts with TFIIA, but is disparate from the domain that interacts with Sp1.
      Repression can be thwarted when stable transcription preinitiation complexes are
      formed before RBP addition, suggesting that RBP interaction with TFIIA and TFIID
      perturbs optimal interactions between these coactivators. Consistent with this,
      interaction between RBP and TFIIA precludes interaction with dTAFII110. This is
      the first report of a repressor specifically targeting these two coactivators to
      subvert activated transcription.

PMID- 9620851
TI  - The histone acetylase PCAF is a nuclear receptor coactivator.
AB  - Whereas the histone acetylase PCAF has been suggested to be part of a coactivator
      complex mediating transcriptional activation by the nuclear hormone receptors,
      the physical and functional interactions between nuclear receptors and PCAF have
      remained unclear. Our efforts to clarify these relationships have revealed two
      novel properties of nuclear receptors. First, we demonstrate that the RXR/RAR
      heterodimer directly recruits PCAF from mammalian cell extracts in a ligand
      dependent manner and that increased expression of PCAF leads to enhanced retinoid
      responsive transcription. Second, we demonstrate that, in vitro, PCAF directly
      associates with the DNA-binding domain of nuclear receptors, independently of
      p300/CBP binding, therefore defining a novel cofactor interaction surface.
      Furthermore, our results show that dissociation of corepressors enables ligand
      dependent PCAF binding to the receptors. This observation illuminates how a
      ligand-dependent receptor function can be propagated to regions outside the
      ligand-binding domain itself. On the basis of these observations, we suggest that
      PCAF may play a more central role in nuclear receptor function than previously
      anticipated.

PMID- 9620852
TI  - Localization-dependent translation requires a functional interaction between the
      5' and 3' ends of oskar mRNA.
AB  - The precise restriction of proteins to specific domains within a cell plays an
      important role in early development and differentiation. An efficient way to
      localize and concentrate proteins is by localization of mRNA in a translationally
      repressed state, followed by activation of translation when the mRNA reaches its
      destination. A central issue is how localized mRNAs are derepressed. In this
      study we demonstrate that, when oskar mRNA reaches the posterior pole of the
      Drosophila oocyte, its translation is derepressed by an active process that
      requires a specific element in the 5' region of the mRNA. We demonstrate that
      this novel type of element is a translational derepressor element, whose
      functional interaction with the previously identified repressor region in the
      oskar 3' UTR is required for activation of oskar mRNA translation at the
      posterior pole. The derepressor element only functions at the posterior pole,
      suggesting that a locally restricted interaction between trans-acting factors and
      the derepressor element may be the link between mRNA localization and
      translational activation. We also show specific interaction of two proteins with
      the oskar mRNA 5' region; one of these also recognizes the 3' repressor element.
      We discuss the possible involvement of these factors as well as known genes in
      the process of localization-dependent translation.

PMID- 9620853
TI  - The surveillance complex interacts with the translation release factors to
      enhance termination and degrade aberrant mRNAs.
AB  - The nonsense-mediated mRNA decay pathway is an example of an evolutionarily
      conserved surveillance pathway that rids the cell of transcripts that contain
      nonsense mutations. The product of the UPF1 gene is a necessary component of the
      putative surveillance complex that recognizes and degrades aberrant mRNAs. Recent
      results indicate that the Upf1p also enhances translation termination at a
      nonsense codon. The results presented here demonstrate that the yeast and human
      forms of the Upf1p interact with both eukaryotic translation termination factors
      eRF1 and eRF3. Consistent with Upf1p interacting with the eRFs, the Upf1p is
      found in the prion-like aggregates that contain eRF1 and eRF3 observed in yeast
      [PSI+] strains. These results suggest that interaction of the Upf1p with the
      peptidyl release factors may be a key event in the assembly of the putative
      surveillance complex that enhances translation termination, monitors whether
      termination has occurred prematurely, and promotes degradation of aberrant
      transcripts.

PMID- 9620854
TI  - Purification and characterization of the nuclear RNase P holoenzyme complex
      reveals extensive subunit overlap with RNase MRP.
AB  - Ribonuclease P (RNase P) is a ribonucleoprotein enzyme that cleaves precursor
      tRNA transcripts to give mature 5' ends. RNase P in eubacteria has a large,
      catalytic RNA subunit and a small protein subunit that are required for precursor
      tRNA cleavage in vivo. Although the eukaryotic holoenzymes have similar, large
      RNA subunits, previous work in a number of systems has suggested that the
      eukaryotic enzymes require a greater protein content. We have purified the
      Saccharomyces cerevisiae nuclear RNase P to apparent homogeneity, allowing the
      first comprehensive analysis of an unexpectedly complex subunit composition.
      Peptide sequencing by ion trap mass spectrometry identifies nine proteins that
      copurify with the nuclear RNase P RNA subunit, totaling 20-fold more protein than
      in the bacterial enzyme. All of these proteins are encoded by genes essential for
      RNase P activity and for cell viability. Previous genetic studies suggested that
      four proteins might be subunits of both RNase P and RNase MRP, the related rRNA
      processing enzyme. We demonstrate that all four of these proteins, Pop1p, Pop3p,
      Pop4p, and Rpp1p, are integral subunits of RNase P. In addition, four of the five
      newly identified protein subunits, Pop5p, Pop6p, Pop7p, and Pop8p, also appear to
      be shared between RNase P and RNase MRP. Only one polypeptide, Rpr2p, is unique
      to the RNase P holoenzyme by genetic depletion and immunoprecipitation studies.
      The large increase in the number of protein subunits over eubacterial RNase P is
      consistent with an increase in functional complexity in eukaryotes. The degree of
      structural similarity between nuclear RNase P and RNase MRP suggests that some
      aspects of their functions in pre-tRNA and pre-rRNA processing pathways might
      overlap or be coordinated.

PMID- 9620855
TI  - Multistep signaling requirements for pituitary organogenesis in vivo.
AB  - During development of the mammalian pituitary gland specific hormone-producing
      cell types, critical in maintaining homeostasis, emerge in a spatially and
      temporally specific fashion from an ectodermal primordium. We have investigated
      the molecular basis of generating diverse pituitary cell phenotypes from a common
      precursor, providing in vivo and in vitro evidence that their development
      involves three sequential phases of signaling events and the action of a gradient
      at an ectodermal boundary. In the first phase, the BMP4 signal from the ventral
      diencephalon, expressing BMP4, Wnt5a, and FGF8, represents a critical dorsal
      neuroepithelial signal for pituitary organ commitment in vivo. Subsequently, a
      BMP2 signal emanates from a ventral pituitary organizing center that forms at the
      boundary of a region of oral ectoderm in which Shh expression is selectively
      excluded. This BMP2 signal together with a dorsal FGF8 signal, appears to create
      opposing activity gradients that are suggested to generate overlapping patterns
      of specific transcription factors underlying cell lineage specification events,
      whereas Wnt4 is needed for the expansion of ventral pituitary cell phenotypes. In
      the third phase, temporally specific loss of the BMP2 signal is required to allow
      terminal differentiation. The consequence of these sequential organ and cellular
      determination events is that each of the hormone-producing pituitary cell types
      gonadotropes, thyrotropes, somatotropes, lactotropes, corticotropes, and
      melanotropes-appear to be determined, in a ventral-to-dorsal gradient,
      respectively.

PMID- 9620856
TI  - Notochord repression of endodermal Sonic hedgehog permits pancreas development.
AB  - Notochord signals to the endoderm are required for development of the chick
      dorsal pancreas. Sonic hedgehog (SHH) is normally absent from pancreatic
      endoderm, and we provide evidence that notochord, in contrast to its effects on
      adjacent neuroectoderm where SHH expression is induced, represses SHH expression
      in adjacent nascent pancreatic endoderm. We identify activin-betaB and FGF2 as
      notochord factors that can repress endodermal SHH and thereby permit expression
      of pancreas genes including Pdx1 and insulin. Endoderm treatment with antibodies
      that block hedgehog activity also results in pancreatic gene expression.
      Prevention of SHH expression in prepancreatic dorsal endoderm by intercellular
      signals, like activin and FGF, may be critical for permitting early steps of
      chick pancreatic development.

PMID- 9620857
TI  - The DNA methylation locus DDM1 is required for maintenance of gene silencing in
      Arabidopsis.
AB  - To investigate the relationship between cytosine methylation and gene silencing
      in Arabidopsis, we constructed strains containing the ddm1 hypomethylation
      mutation and a methylated and silenced PAI2 tryptophan biosynthetic gene (MePAI2)
      that results in a blue fluorescent plant phenotype. The ddm1 mutation had both an
      immediate and a progressive effect on PAI gene silencing. In the first
      generation, homozygous ddm1 MePAI2 plants displayed a weakly fluorescent
      phenotype, in contrast to the strongly fluorescent phenotype of the DDM1 MePAI2
      parent. After two generations of inbreeding by self-pollination, the ddm1/ddm1
      lines became nonfluorescent. The progressive loss of fluorescence correlated with
      a progressive loss of methylation from the PAI2 gene. These results indicate that
      methylation is necessary for maintenance of PAI gene silencing and that
      intermediate levels of DNA methylation are associated with intermediate gene
      silencing. The results also support our earlier hypothesis that ddm1 homozygotes
      act as "epigenetic mutators" by accumulating heritable changes in DNA methylation
      that can lead to changes in gene expression.

PMID- 9620858
TI  - Mcm1 regulates donor preference controlled by the recombination enhancer in
      Saccharomyces mating-type switching.
AB  - Switching of Saccharomyces mating type by replacement of sequences at the MAT
      locus involves a choice between two donors, HML and HMR. MATalpha cells inhibit
      recombination along the entire left arm of chromosome III, including HML, whereas
      MATa cells activate this same region. MATa-dependent activation of HML depends on
      a small, cis-acting DNA sequence designated the recombination enhancer (RE),
      located 17 kb centromere-proximal to HML. A comparison of RE sequences
      interchangeable between Saccharomyces cerevisiae and Saccharomyces carlsbergensis
      defines a minimum RE of 244 bp. RE activity is repressed in MATalpha cells by
      binding of the Matalpha2-Mcm1 corepressor to a site within the RE. Mutation of
      the two Matalpha2 binding sites removes most, but not all, of this repression,
      and RE chromatin structure in MATalpha cells becomes indistinguishable from that
      seen in MATa. Surprisingly, a 2-bp mutation in the Mcm1 binding site completely
      abolishes RE activity in MATa cells; moreover, RE chromatin structure in the MATa
      mutant becomes very similar to that seen in MATalpha cells with a normal RE,
      displaying highly ordered nucleosomes despite the absence of Matalpha2. Further,
      a mutation that alters the ability of Mcm1 to act with Matalpha2 in repressing a
      specific genes also alters donor preference in either mating type. Thus, Mcm1 is
      critically responsible for the activation as well as the Matalpha2-Mcm1-mediated
      repression of RE activity.

PMID- 9620859
TI  - A novel Myb homolog initiates Dictyostelium development by induction of adenylyl
      cyclase expression.
AB  - Dictyostelium development is induced by starvation. The adenylyl cyclase gene ACA
      is one of the first genes expressed upon starvation. ACA produces extracellular
      cAMP that induces chemotaxis, aggregation, and differentiation in neighboring
      cells. Using insertional mutagenesis we have isolated a mutant that does not
      aggregate upon starvation but is rescued by adding extracellular cAMP. Sequencing
      of the mutated locus revealed a new gene, DdMYB2, whose product contains three
      Myb repeats, the DNA-binding motif of Myb-related transcription factors. Ddmyb2
      null cells show undetectable levels of ACA transcript and no cAMP production.
      Ectopic expression of ACA from a constitutive promotor rescues differentiation
      and morphogenesis of Ddmyb2-null mutants. The results suggest that development in
      Dictyostelium starts by starvation-mediated DdMyb2 activation, which induces
      adenylyl cyclase activity producing the differentiation-inducing signal cAMP.

PMID- 9620861
TI  - Unmediated heterogeneous electron transfer reaction of ascorbate oxidase and
      laccase at a gold electrode.
AB  - The unmediated electrochemistry of two large Cu-containing proteins, ascorbate
      oxidase and laccase, was investigated by direct-current cyclic voltammetry. Rapid
      heterogeneous electron transfer was achieved in the absence of promoters or
      mediators by trapping a small amount of protein within a solid, electrochemically
      inert, tributylmethyl phosphonium chloride membrane coating a gold electrode. The
      problems typical of proteins in solution, such as adsorption on the electrode
      surface, were avoided by this procedure. In anaerobic conditions, the cyclic
      voltammograms, run at a scan rate of up to 200 mV/s, showed the electron transfer
      process to be quasi-reversible and diffusion-controlled. The pH-dependent redox
      potentials (+360 mV and +400 mV against a normal hydrogen electrode at pH7.0 for
      ascorbate oxidase and laccase respectively and +390 mV and +410 mV at pH5.5) were
      similar to those of the free proteins. The same electrochemical behaviour was
      recorded for the type 2 Cu-depleted derivatives, which contain reduced type 3 Cu,
      whereas the apoproteins were electrochemically inactive. Under aerobic conditions
      the catalytic current intensity of holoprotein voltammograms increased up to
      approx. 2-fold at a low scanning rate, with unchanged redox potentials. The
      voltammograms of type 2 Cu-depleted proteins and of apoproteins were unaffected
      by the presence of oxygen. This suggests that electron uptake at the electrode
      surface involves type 1 Cu and that only in the presence of oxygen is the
      intramolecular electron transfer to other protein sites rapid enough to be
      observed. The analogy with available kinetic results is discussed.

PMID- 9620862
TI  - Hypochlorite-induced damage to proteins: formation of nitrogen-centred radicals
      from lysine residues and their role in protein fragmentation.
AB  - Stimulated monocytes and neutrophils generate hypochlorite (HOCl) via the release
      of the enzyme myeloperoxidase and hydrogen peroxide. HOCl damages proteins by
      reaction with amino acid side-chains or backbone cleavage. Little information is
      available about the mechanisms and intermediates involved in these reactions. EPR
      spin trapping has been employed to identify radicals on proteins, peptides and
      amino acids after treatment with HOCl. Reaction with HOCl gives both high- and
      low-molecular-mass nitrogen-centred, protein-derived radicals; the yield of the
      latter increases with both higher HOCl:protein ratios and enzymic digestion.
      These radicals, which arise from lysine side-chain amino groups, react with
      ascorbate, glutathione and Trolox. Reaction of HOCl-treated proteins with excess
      methionine eliminates radical formation, which is consistent with lysine-derived
      chloramines (via homolysis of N-Cl bonds) being the radical source. Incubation of
      HOCl-treated proteins, after removal of excess oxidant, gives rise to both
      nitrogen-centred radicals, over a period of hours, and time-dependent
      fragmentation of the protein. Treatment with excess methionine or antioxidants
      (Trolox, ascorbate, glutathione) protects against fragmentation; urate and
      bilirubin do not. Chloramine formation and nitrogen-centred radicals are
      therefore key species in HOCl-induced protein fragmentation.

PMID- 9620863
TI  - The relationship of oxygen delivery to absolute haemoglobin oxygenation and
      mitochondrial cytochrome oxidase redox state in the adult brain: a near-infrared
      spectroscopy study.
AB  - Near-infrared spectroscopy was used to determine the effect of changes in the
      rate of oxygen delivery to the adult rat brain on the absolute concentrations of
      oxyhaemoglobin, deoxyhaemoglobin and the redox state of the CuA centre in
      mitochondrial cytochrome oxidase. The cytochrome oxidase detection algorithm was
      determined to be robust to large changes in haemoglobin oxygenation and
      concentration. By assuming complete haemoglobin deoxygenation and CuA reduction
      following mechanical ventilation on 100% N2O, the absolute concentration of
      oxyhaemoglobin (35 microM), deoxyhaemoglobin (27 microM) and the redox state of
      CuA (82% oxidized) were calculated in the normal adult brain. The mean arterial
      blood pressure was decreased by exsanguination. When the pressure reached 100
      mmHg, haemoglobin oxygenation started to fall, but the total haemoglobin
      concentration and oxidized CuA levels only fell when cerebral blood volume
      autoregulation mechanisms failed at 50 mmHg. Haemoglobin oxygenation fell
      linearly with decreases in the rate of oxygen delivery to the brain, but the
      oxidized CuA concentration did not start to fall until this rate was 50% of
      normal. The results suggest that the brain maintains more than adequate oxygen
      delivery to mitochondria and that near-infrared spectroscopy may be a good
      measure of oxygen insufficiency in vivo.

PMID- 9620864
TI  - Re-examination of the roles of PEP and Mg2+ in the reaction catalysed by the
      phosphorylated and non-phosphorylated forms of phosphoenolpyruvate carboxylase
      from leaves of Zea mays. Effects of the activators glucose 6-phosphate and
      glycine.
AB  - To study the effects of phosphoenolpyruvate (PEP) and Mg2+ on the activity of the
      non-phosphorylated and phosphorylated forms of phosphoenolpyruvate carboxylase
      (PEPC) from Zea mays leaves, steady-state measurements have been carried out with
      the free forms of PEP (fPEP) and Mg2+ (fMg2+), both in a near-physiological
      concentration range. At pH 7.3, in the absence of activators, the initial
      velocity data obtained with both forms of the enzyme are consistent with the
      exclusive binding of MgPEP to the active site and of fPEP to an activating
      allosteric site. At pH 8.3, and in the presence of saturating concentrations of
      glucose 6-phosphate (Glc6P) or Gly, the free species also combined with the
      active site in the free enzyme, but with dissociation constants at least 35-fold
      that estimated for MgPEP. The latter dissociation constant was lowered to the
      same extent by saturating Glc6P and Gly, to approx. one-tenth and one-sixteenth
      in the non-phosphorylated and phosphorylated enzymes respectively. When Glc6P is
      present, fPEP binds to the active site in the free enzyme better than fMg2+,
      whereas the metal ion binds better in the presence of Gly. Saturation of the
      enzyme with Glc6P abolished the activation by fPEP, consistent with a common
      binding site, whereas saturation with Gly increased the affinity of the
      allosteric site for fPEP. Under all the conditions tested, our results suggest
      that fPEP is not able to combine with the allosteric site in the free enzyme,
      i.e. it cannot combine until after MgPEP, fPEP or fMg2+ are bound at the active
      site. The physiological role of Mg2+ in the regulation of the enzyme is only that
      of a substrate, mainly as part of the MgPEP complex. The kinetic properties of
      maize leaf PEPC reported here are consistent with the enzyme being well below
      saturation under the physiological concentrations of fMg2+ and PEP, particularly
      during the dark period; it is therefore suggested that the basal PEPC activity in
      vivo is very low, but highly responsive to even small changes in the
      intracellular concentration of its substrate and effectors.

PMID- 9620860
TI  - Sorting and storage during secretory granule biogenesis: looking backward and
      looking forward.
AB  - Secretory granules are specialized intracellular organelles that serve as a
      storage pool for selected secretory products. The exocytosis of secretory
      granules is markedly amplified under physiologically stimulated conditions. While
      granules have been recognized as post-Golgi carriers for almost 40 years, the
      molecular mechanisms involved in their formation from the trans-Golgi network are
      only beginning to be defined. This review summarizes and evaluates current
      information about how secretory proteins are thought to be sorted for the
      regulated secretory pathway and how these activities are positioned with respect
      to other post-Golgi sorting events that must occur in parallel. In the first half
      of the review, the emerging role of immature secretory granules in protein
      sorting is highlighted. The second half of the review summarizes what is known
      about the composition of granule membranes. The numerous similarities and
      relatively limited differences identified between granule membranes and other
      vesicular carriers that convey products to and from the plasmalemma, serve as a
      basis for examining how granule membrane composition might be established and how
      its unique functions interface with general post-Golgi membrane traffic. Studies
      of granule formation in vitro offer additional new insights, but also important
      challenges for future efforts to understand how regulated secretory pathways are
      constructed and maintained.

PMID- 9620865
TI  - Binding of human alpha-thrombin to platelet GpIb: energetics and functional
      effects.
AB  - Thrombin interaction with platelet glycocalicin (GC), the 140 kDa
      extracytoplasmic fragment of the membrane glycoprotein Ib, was investigated by
      using a solid-phase assay. Thrombin bound to GC-coated polystyrene wells was
      detected by measuring the hydrolysis of a chromogenic substrate. The monoclonal
      antibody LJ-Ib10, which specifically binds to the thrombin-binding site of GC,
      could displace thrombin from immobilized GC, whereas the monoclonal antibody LJ
      Ib1, which interacts with the von Willebrand factor-binding domain of GC, did not
      affect thrombin binding to GC. Competitive inhibition of thrombin binding to
      immobilized GC was also observed using GC in solution or ligands that bind to the
      thrombin heparin-binding site, such as heparin and prothrombin fragment 2.
      Furthermore functional experiments demonstrated that GC binding to thrombin
      competes with heparin for thrombin inactivation by the antithrombin III-heparin
      complex as well. Thrombin-GC interaction was also studied as a function of
      temperature over the range 4-37 degreesC. A large negative heat capacity change
      (DeltaCp), of -4.14+/-0.8 kJ.mol-1.K-1, was demonstrated to dominate the
      thermodynamics of thrombin-GC complex-formation. Finally it was demonstrated that
      GC binding to thrombin can allosterically decrease the enzyme affinity for
      hirudin via a simultaneous decrease in association rate and increase in the
      dissociation velocity of the enzyme-inhibitor adduct. Together these observations
      indicate the GC binding to the heparin-binding domain of thrombin is largely
      driven by a hydrophobic effect and that such interaction can protect the enzyme
      from inhibition by the heparin-anti-thrombin III complex.

PMID- 9620866
TI  - Structure and activity of mouse S-adenosylmethionine decarboxylase gene promoters
      and properties of the encoded proteins.
AB  - The promoter regions of two S-adenosylmethionine decarboxylase genes (AMD genes)
      were isolated from a mouse genomic library. One promoter was that of the bona
      fide mouse AMD gene (AMD1) whereas the other was that of the intronless AMD gene
      (AMD2). There was no sequence identity between the two promoters. The sequence of
      the AMD1 promoter was highly homologous to the human AMD1 and rat Amd1B
      promoters. After transient transfection in various cell lines, the AMD1 promoter
      was one to two orders of magnitude stronger than the AMD2 promoter. Similar
      results were obtained by using stably transfected mouse FM3A cells. In S
      adenosylmethionine decarboxylase (AdoMetDC)-overproducing SAM-1 cells, the AMD1
      gene was amplified over 5-fold. AdoMetDC encoded by the intronless AMD2 gene had
      two amino acid replacements (Met to Ile at codon 70 and Ala to Val at codon 139),
      compared with the protein encoded by the AMD1 gene, and exhibited decreased
      catalytic activity (<50%) and decreased processing activity when expressed in
      AdoMetDC-deficient Escherichia coli cells. When Ile-70 of the protein encoded by
      AMD2 was converted into Met, both the catalytic and processing activities
      recovered markedly, indicating that Met-70 adjacent to the proenzyme-processing
      site is important for both activities. The third AMD locus (AMD3) in FM3A cells
      contains a pseudogene, in which deletion of two bases generates a premature
      termination codon at position 57. Since the AMD2 promoter had only 1-10% of the
      strength of the bona fide AMD1 gene and AMD2 protein possessed lower specific
      activity, the relative contribution of the AMD2-encoded enzyme to total AdoMetDC
      activity is small. Thus AdoMetDC activity in murine cells is thought to be due
      mainly to the product of the AMD1 gene.

PMID- 9620867
TI  - Inhibition of etoposide-induced apoptosis with peptide aldehyde inhibitors of
      proteasome.
AB  - Recent investigations have indicated the involvement of proteasome in programmed
      cell death. The present studies show that although peptide aldehyde inhibitors of
      proteasome are by themselves weak inducers of apoptosis, they inhibit the
      apoptotic effect of the anticancer drug etoposide in rat thymocytes. Acetyl-Leu
      Leu-norvalinal (LLnV-al) and other related peptide aldehydes inhibited the
      increase in caspase activity and DNA fragmentation that followed treatment with
      etoposide and their effect was related to their potency as proteasome inhibitors.
      To inhibit etoposide-induced apoptosis, LLnV-al must be present within 3 h of
      treatment with etoposide, in the same way as the inhibitor of protein synthesis
      cycloheximide must be. Etoposide caused a rapid accumulation of p53 protein that
      was not inhibited by LLnV-al, which was also a strong inducer of p53. Peptide
      aldehydes were also weak activators of caspase activity, suggesting that the same
      mechanism, i.e. the blocking of proteasome function, both triggers apoptosis and
      inhibits the effect of etoposide. These results are consistent with a model in
      which proteasome is selectively involved in the pathway used by etoposide to
      induce cell suicide.

PMID- 9620868
TI  - The intracellular triacylglycerol/fatty acid cycle: a comparison of its activity
      in hepatocytes which secrete exclusively apolipoprotein (apo) B100 very-low
      density lipoprotein (VLDL) and in those which secrete predominantly apoB48 VLDL.
AB  - Hamster hepatocytes, like human hepatocytes, secrete triacylglycerol (TAG) as
      very-low-density lipoprotein (VLDL) in association with apolipoprotein (apo)
      B100, whereas in the rat, TAG is secreted predominantly in association with
      apoB48. Nevertheless, in hepatocytes from both species, a minimum of between 60%
      and 70% [69. 1+/-1.4% (hamster), 60.6+/-2.5% (rat)] of the VLDL TAG was secreted
      following lipolysis and re-esterification of intracellular TAG. The fractional
      rates of hepatocellular TAG turnover (lipolysis and re-esterification) were
      similar in both species [1.83+/-0.28 pools/24 h (hamster), 1.39+/-0.23 pools/24 h
      (rat)]. Comparison of the relative changes in the 3H and 14C specific
      radioactivities of the VLDL and cellular TAG, pre-labelled with [3H]glycerol and
      [4C]oleate, suggested that fatty acids released by lipolysis either were
      recruited directly into a VLDL assembly pool or were recycled to the cellular
      pool following re-esterification. Recycling in the hamster was somewhat greater
      than in the rat (66.1+/-5.7% versus 53. 7+/-4.8% of TAG lipolysed respectively).
      Similarly, a larger proportion of newly synthesized TAG was retained within the
      cell, rather than secreted as VLDL, in the hamster compared with the rat (37.9+/
      2.8% versus 20+/-3.8%, P<0.01). These factors may have contributed to the
      somewhat lower rate of VLDL TAG secretion in the hamster hepatocytes compared
      with those from the rat (43.3+/-4.2 versus 96.4+/-3.4 microg/24 h per mg of cell
      protein). Rat hepatocytes were more sensitive to inhibition of VLDL secretion by
      insulin than were those from hamster. In neither case did insulin affect total or
      fractional TAG turnover. The results suggest that assembly of both apoB100 VLDL
      and apoB48 VLDL is associated with efficient intracellular TAG lipolysis.

PMID- 9620870
TI  - Functional analysis of the human annexin I and VI gene promoters.
AB  - To gain insight into the molecular basis of annexin gene expression we have
      analysed the annexin I and VI gene promoters. A previously described 881 bp
      sequence immediately upstream of the annexin I transcription start site and a
      similar size fragment proximal to the annexin VI transcription start site both
      drove expression of the luciferase reporter gene in fibroblasts and epithelial
      cells. Neither promoter displayed any sensitivity to dexamethasone, suggesting
      that the putative glucocorticoid response element in the annexin I promoter is
      non-functional. Consistent with this, endogenous annexin I gene expression was
      unaffected by dexamethasone at the mRNA and protein levels in A431 cells. A
      series of 5' deletions of the two promoters were examined to define the minimal
      active sequences. For annexin I this corresponded to a sequence approx. 150 bp
      upstream of the transcription start site that included CAAT and TATA boxes.
      Unexpectedly, the annexin VI promoter, which also contains CAAT and TATA boxes,
      was fully active in the absence of these elements, a 53 bp sequence between these
      boxes and the transcription start site having maximal activity. Electrophoretic
      mobility-shift assays with nuclear extracts from A431 and HeLa cells with probes
      corresponding to this region revealed an SP1-binding site. These results show
      that the annexin I and VI genes have individual modes of transcriptional
      regulation and that if either annexin I or annexin VI has an anti-inflammatory
      role, then this is in the absence of steroid-induced gene expression.

PMID- 9620869
TI  - Functional implications of nitric oxide produced by mitochondria in mitochondrial
      metabolism.
AB  - The effects of endogenous production of NO., catalysed by the mitochondrial
      nitric oxide synthase (NOS), on mitochondrial metabolism were studied. The
      respiratory rates of intact mitochondria in State 4 were decreased by 40% and 28%
      with succinate and malate-glutamate, respectively, in the presence of L-arginine
      (L-Arg); conversely, the O2 uptake with NG-methyl-L-arginine (NMMA), a
      competitive inhibitor of NOS, was increased. The production of NO. and the
      inhibition of the respiratory rates were dependent on the metabolic state in
      which mitochondria were maintained: NO. production was probably supported by
      mitochondrial NADPH, the latter maintained by the energy-dependent
      transhydrogenase. In addition to the decline in the respiratory rate, an
      inhibition of ATP synthesis was also observed (40-50%) following supplementation
      with L-Arg. The dependence of the respiratory rates of mitochondria in State 3
      and cytochrome oxidase activities on O2 concentrations with either L-Arg or NMMA
      indicated that both processes were competitively inhibited by NO. at the
      cytochrome oxidase level. This inhibition can be explained by the interaction of
      NO. with cytochrome oxidase at the binuclear centre. The role of NO. as a
      physiological modulator of cytochrome oxidase is discussed in terms of cellular
      metabolism.

PMID- 9620871
TI  - Molecular basis of non-responsiveness to peroxisome proliferators: the guinea-pig
      PPARalpha is functional and mediates peroxisome proliferator-induced
      hypolipidaemia.
AB  - The guinea pig does not undergo peroxisome proliferation in response to
      peroxisome proliferators, in contrast with other rodents. To understand the
      molecular basis of this phenotype, the peroxisome proliferator activated receptor
      alpha (PPARalpha) from guinea-pig liver was cloned; it encodes a protein of 467
      amino acid residues that is similar to rodent and human PPARalpha. The guinea-pig
      PPARalpha showed a high substitution rate: maximum likelihood analysis was
      consistent with rodent monophyly, but could not exclude rodent polyphyly (P
      approximately 0.06). The guinea-pig PPARalpha cDNA was expressed in 293 cells and
      mediated the induction of the luciferase reporter gene by the peroxisome
      proliferator, Wy-14,643, dependent on the presence of a peroxisome proliferator
      response element. Moreover the PPARalpha RNA and protein were expressed in guinea
      pig liver, although at lower levels than in a species which is responsive to
      peroxisome proliferators, the mouse. To determine whether the guinea-pig
      PPARalpha mediated any physiological effects, guinea pigs were exposed to two
      selective PPARalpha agonists, Wy-14, 643 and methylclofenapate; both compounds
      induced hypolipidaemia. Thus the guinea pig is a useful model for human responses
      to peroxisome proliferators.

PMID- 9620872
TI  - Functional expression of a vacuolar-type H+-ATPase in the plasma membrane and
      intracellular vacuoles of Trypanosoma cruzi.
AB  - Acid-loaded Trypanosoma cruzi amastigotes and trypomastigotes regained normal
      cytoplasmic pH (pHi), as measured in cells loaded with 2',7'-bis-(2-carboxyethyl)
      5(6)-carboxyfluorescein (BCECF), by a process that was sensitive to bafilomycin
      A1 at concentrations comparable to those that inhibited vacuolar (V) H+-ATPases
      from different sources. Steady-state pHi was also decreased by similar
      concentrations of bafilomycin A1 in a concentration-dependent manner. The efflux
      of H+ equivalents from amastigotes and trypomastigotes was measured by following
      changes in the fluorescence of extracellular BCECF. Basal H+ extrusion in the
      presence of glucose was 15.4+/-2.8 (S.D.) nmol of H+/min per 10(8) amastigotes
      and 6. 37+/-0.8 nmol of H+/min per 10(8) trypomastigotes. Bafilomycin A1
      treatment significantly decreased the efflux of H+ equivalents by amastigotes
      (8.9+/-2.2 nmol of H+/min per 10(8) cells), but not by trypomastigotes (5.1+/-1.7
      nmol of H+/min per 10(8) cells). The localization of the V-H+-ATPase of T. cruzi
      was investigated by immunocytochemistry. Confocal and electron microscopy
      indicated that, in addition to being located in cytoplasmic vacuoles, the V-H+
      ATPase of different stages of T. cruzi is also located in the plasma membrane.
      However, no labelling was detected in the plasma membrane lining the flagellar
      pocket of the different developmental stages. Surface localization of the V-H+
      ATPase was confirmed by experiments involving the biotinylation of cell surface
      proteins and immunoprecipitation with antibodies against the V-H+-ATPase. Taken
      together, the results are consistent with the presence of a functional V-H+
      ATPase in the plasma membrane of amastigotes and with an important role for
      intracellular acidic compartments in the maintenance of pHi in different stages
      of T. cruzi.

PMID- 9620873
TI  - Heat-shock protein-25/27 phosphorylation by the delta isoform of protein kinase
      C.
AB  - Small heat-shock proteins (sHSPs) are widely expressed 25-28 kDa proteins whose
      functions are dynamically regulated by phosphorylation. While recent efforts have
      clearly delineated a stress-responsive p38 mitogen-activated protein-kinase
      (MAPK)-dependent kinase pathway culminating in activation of the heat-shock (HSP)
      kinases, mitogen-activated protein-kinase-activated protein kinase-2 and -3, not
      all sHSP phosphorylation events can be explained by the p38 MAPK-dependent
      pathway. The contribution of protein kinase C (PKC) to sHSP phosphorylation was
      suggested by early studies but later questioned on the basis of the reported poor
      ability of purified PKC to phosphorylate sHSP in vitro. The current study re
      evaluates the role of PKC in sHSP phosphorylation in the light of the isoform
      complexity of the PKC family. We evaluated the sHSP phosphorylation status in rat
      corpora lutea obtained from two stages of pregnancy, mid-pregnancy and late
      pregnancy, which express different levels of the novel PKC isoform, PKC-delta.
      Two-dimensional Western blot analysis showed that HSP-27 was more highly
      phosphorylated in vivo in corpora lutea of late pregnancy, corresponding to the
      developmental stage in which PKC-delta is abundant and active. Late-pregnant
      luteal extracts contained a lipid-sensitive HSP-kinase activity which exactly co
      purified with PKC-delta using hydroxyapatite and S-Sepharose column
      chromatography. To determine whether there might be preferential phosphorylation
      of sHSP by a particular PKC isoform, purified recombinant PKC isoforms
      corresponding to those PKC isoforms detected in rat corpora lutea were evaluated
      for HSP-kinase activity in vitro. Recombinant PKC-delta effectively catalysed the
      phosphorylation of sHSP in vitro, and PKC-alpha was 30-50% as effective as an HSP
      kinase; other PKCs tested (beta1, beta2, epsilon and zeta) were poor HSP-kinases.
      These results show that select PKC family members can function as direct HSP
      kinases in vitro. Moreover, the observation of enhanced luteal HSP-27
      phosphorylation in vivo, in late pregnancy, when PKC-delta is abundant and
      active, suggests that select PKC family members contribute to sHSP
      phosphorylation events in vivo.

PMID- 9620874
TI  - Molecular cloning and expression of a cDNA encoding an apoptotic endonuclease
      DNase gamma.
AB  - An endonuclease named DNase gamma has been purified from the nuclei of apoptotic
      rat thymocytes [Shiokawa, Ohyama, Yamada and Tanuma (1997) Biochem. J. 326, 675
      681]. Here we report the molecular cloning of a cDNA encoding a 35 kDa precursor
      protein for rat DNase gamma. A 1.6 kb mRNA coding for the DNase gamma precursor
      is detected at high levels in spleen, lymph nodes, thymus and liver. By using
      reverse transcriptase-mediated PCR, expression of DNase gamma mRNA is observed in
      kidney and testis but not in brain or heart. Analysis of recombinant DNase gamma
      reveals that full-length DNase gamma, including the N-terminal precursor, is an
      inactive proenzyme. The mature form of recombinant DNase gamma, from which the N
      terminal precursor has been removed, has the same properties as purified DNase
      gamma: requirement for divalent cations, dependence on pH, sensitivity to Zn2+,
      and cleavage of chromosome DNA to nucleosomal units. In HeLa S3 cells stably
      transfected with the DNase gamma cDNA, exogenously introduced DNase gamma is
      activated by apoptotic stimuli; enhancement of DNA fragmentation, chromatin
      condensation and nuclear collapse are observed. These findings provide evidence
      for the involvement of DNase gamma in DNA fragmentation and nuclear structural
      changes during apoptosis.

PMID- 9620875
TI  - Adenoviral expression of murine serum amyloid A proteins to study amyloid
      fibrillogenesis.
AB  - Serum amyloid A (SAA) proteins are one of the most inducible acute-phase
      reactants and are precursors of secondary amyloidosis. In the mouse, SAA1 and
      SAA2 are induced in approximately equal quantities in response to amyloid
      induction models. These two isotypes differ in only 9 of 103 amino acid residues;
      however, only SAA2 is selectively deposited into amyloid fibrils. SAA expression
      in the CE/J mouse species is an exception in that gene duplication did not occur
      and the CE/J variant is a hybrid molecule sharing features of SAA1 and SAA2.
      However, even though it is more closely related to SAA2 it is not deposited as
      amyloid fibrils. We have developed an adenoviral vector system to overexpress SAA
      proteins in cell culture to determine the ability of these proteins to form
      amyloid fibrils, and to study the structural features in relation to amyloid
      formation. Both the SAA2 and CE/J SAA proteins were synthesized in large
      quantities and purified to homogeneity. Electron microscopic analysis of the SAA
      proteins revealed that the SAA2 protein was capable of forming amyloid fibrils,
      whereas the CE/J SAA was incapable. Radiolabelled SAAs were associated with
      normal or acute-phase high-density lipoproteins (HDLs); we examined them for
      their clearance from the circulation. In normal mice, SAA2 had a half-life of 70
      min and CE/J SAA had a half-life of 120 min; however, in amyloid mice 50% of the
      SAA2 cleared in 55 min, compared with 135 min for the CE/J protein. When the SAA
      proteins were associated with acute-phase HDLs, SAA2 clearance was decreased to
      60 min in normal mice compared with 30 min in amyloidogenic mice. Both normal and
      acute-phase HDLs were capable of depositing SAA2 into preformed amyloid fibrils,
      whereas the CE/J protein did not become associated with amyloid fibrils. This
      established approach opens the doors for large-scale SAA production and for the
      examination of specific amino acids involved in the fibrillogenic capability of
      the SAA2 molecule in vitro and in vivo.

PMID- 9620876
TI  - Genomic organization of the 3'-region of the human MUC5AC mucin gene: additional
      evidence for a common ancestral gene for the 11p15.5 mucin gene family.
AB  - The human mucin gene MUC5AC is mapped clustered with MUC2, MUC5B and MUC6 on
      chromosome 11p15.5. We report here the isolation and characterization of a
      genomic cosmid clone, designated ELO9, spanning the 3'-region of MUC5AC and the
      5'-region of MUC5B, allowing us to conclude that MUC5AC and MUC5B have the same
      transcriptional orientation. We determined the genomic organization and the
      entire sequence of the 3'-region of MUC5AC. The comparative molecular analysis of
      MUC5AC and MUC5B points to a remarkable similarity in the size and the
      distribution of exons, and in the type of splice sites, supporting the notion
      that MUC5AC and MUC5B have evolved from a single common ancestral gene. The
      derivation of the four genes of the 11p15.5 mucin gene family from a single
      ancestral gene is discussed.

PMID- 9620877
TI  - Human mucin gene MUC4: organization of its 5'-region and polymorphism of its
      central tandem repeat array.
AB  - In a previous study we isolated a partial cDNA with a tandem repeat of 48 bp,
      which allowed us to map a novel human mucin gene named MUC4 to chromosome 3q29.
      Here we report the organization and sequence of the 5'-region and its junction
      with the tandem repeat array of MUC4. Analysis of three overlapping genomic
      clones allowed us to obtain a partial restriction map of MUC4 and to locate the
      complete 48 bp tandem repeat domain on a PstI/EcoRI genomic fragment that
      exhibits a very large variation in number of tandem repeats (7-19 kb). cDNA
      clonal extension allowed us to obtain the entire 5' coding region of MUC4. Exon 1
      consists of a 5' untranslated region and an 82 bp fragment encoding the signal
      peptide. This latter shows a high degree of similarity to the signal peptide of
      another apomucin, ASGP-1. Exon 2 is extremely large and contains a unique
      sequence that is followed by the whole tandem repeat domain. It encodes only one
      cysteine residue, making MUC4 different from mucin genes belonging to the 11p15.5
      family. Moreover, an intron downstream from the tandem repeat array consists
      mainly of a 15 bp tandem repeat that exhibits a polymorphism in having a variable
      number of tandem repeats.

PMID- 9620878
TI  - Simultaneous binding of PA28 and PA700 activators to 20 S proteasomes.
AB  - Two activators, named PA700 and PA28, are known to bind to 20 S proteasomes,
      forming two different complexes. The PA700-proteasome complex, also known as the
      26 S proteasome, can degrade intact proteins, whereas complexes with PA28 can
      degrade only peptides. Monoclonal antibodies to 20 S proteasomes or the p45
      ATPase subunit (Trip1, Sug1) of PA700 precipitated the same set of proteins from
      HeLa extracts, including six different ATPase subunits of PA700. This shows that
      p45 is not present in other protein complexes and suggests that all 26 S
      proteasome particles contain the same set of ATPase subunits. Interferons alpha
      and gamma had no effect on the composition of the 26 S proteasome, except for the
      replacement of subunits delta, MB1 and Z with Lmp2, Lmp7 and MECL1 respectively.
      Surprisingly, antibodies to PA28 precipitated p42, a component of PA700.
      Conversely, anti-p45 antibodies precipitated not only 26 S proteasomes but also
      PA28 alpha, beta and gamma, indicating that 20 S proteasomes can simultaneously
      bind both PA700 and PA28. PA28 alpha beta is known to be involved in antigen
      presentation. Conceivably, intact substrate proteins are recognized by PA700 and
      fed into proteasomes whose cleavage specificity is optimized for antigen
      presentation on MHC class I by PA28 and three interferon inducible proteasome
      subunits.

PMID- 9620879
TI  - Reaction of soluble penicillin-binding protein 2a of methicillin-resistant
      Staphylococcus aureus with beta-lactams and acyclic substrates: kinetics in
      homogeneous solution.
AB  - The kinetics of reaction of solubilized penicillin-binding protein 2a (sPBP2a) of
      methicillin-resistant Staphylococcus aureus with a variety of beta-lactams and
      acyclic species was studied in homogeneous aqueous solution at 37 degreesC in 25
      mM Hepes buffer, pH7.0, containing 1 M NaCl. Under these conditions, but not at
      lower salt concentrations, protein precipitation did not occur either during or
      after the reaction. The reactions of beta-lactams in general could be monitored
      by competition with a chromophoric beta-lactam, nitrocefin, or directly in
      certain cases by protein fluorescence. Rate constants for reaction of a wide
      variety of beta-lactams are reported. The interactions are characterized by a
      slow second-order acylation reaction followed by a slower deacylation. For
      example, the rate constants for benzylpenicillin were 12 M-1.s-1 and 3x10(-5) s-1
      respectively. The acylation is slow in comparison with those of normal non
      resistant high-molecular-mass penicillin-binding proteins. sPBP2a also seemed to
      catalyse the slow hydrolysis of a variety of acyclic depsipeptides but not that
      of a d-Ala-d-Ala peptide. The reactions with certain depsipeptides also led to
      protein precipitation. These reactions were, however, not affected by prior
      blockage of the beta-lactam-binding site by benzylpenicillin and thus might take
      place elsewhere on the enzyme. Two classes of potential transition- state
      analogue inhibitors, phosphonate monoesters and boronates, seemed to have little
      effect on the rate of reaction of sPBP2a with nitrocefin and therefore seem to
      have little affinity for the beta-lactam-binding/D,D-peptidase site.

PMID- 9620880
TI  - Growth hormone- and testosterone-dependent regulation of glutathione transferase
      subunit A5 in rat liver.
AB  - The class Alpha glutathione S-transferase (GST) subunit A5 is expressed in the
      livers of young male and female rats. After sexual maturation, this protein is no
      longer detectable in the livers of male rats, but is still expressed in female
      rats. We have previously demonstrated that the sexually dimorphic secretion of
      growth hormone regulates the levels of certain class Mu GSTs in rat liver, and
      this study was designed to investigate the hormonal regulation of GSTA5. Control
      and hypophysectomized rats of both sexes were used to study the role of growth
      hormone in the regulation of hepatic GSTA5; and the influence of testosterone on
      the expression of this same subunit was investigated in intact females and
      castrated males. Liver cytosols were subjected to SDS/PAGE and immunoblotting
      using antibodies directed towards rat (r)GSTA5, and to affinity purification on
      glutathione-Sepharose followed by reverse-phase HPLC in order to quantify the
      relative levels of rGSTA1, A2, A3, A4, M1 and M2 subunits. These analyses
      revealed that the expression of rGSTA5 is, indeed, regulated by both growth
      hormone and testosterone.

PMID- 9620881
TI  - Polarized Ca2+ release in saponin-permeabilized parotid acinar cells evoked by
      flash photolysis of 'caged' inositol 1,4,5-trisphosphate.
AB  - In exocrine acinar cells, agonist stimulation results in a polarized Ca2+ signal,
      termed the 'Ca2+ wave', that propagates from the apical pole towards the
      basolateral region. We attempted to detect the inositol 1,4,5-trisphosphate
      (InsP3)-induced Ca2+ wave in saponin-permeabilized rat parotid acinar cells using
      a digital imaging system. The permeabilized acinar cells were labelled with the
      membrane-bound Ca2+ indicator Calcium Green C18 to detect changes in Ca2+
      concentration adjacent to the membrane of intracellular organelles. Application
      of InsP3 was made by the photolysis of InsP3 P4(5)-1-(2-nitrophenyl)ethyl ester
      (caged InsP3) to expose simultaneously all regions of the permeabilized acinar
      cells to InsP3. The increase in fluorescence ratio following the photolysis of
      0.5 microM caged InsP3 started at the apical region of the acinar cells within
      0.1 s and spread towards the basolateral region, indicating that Ca2+ release
      from intracellular Ca2+ stores was initially evoked at the apical region.
      Pretreatment with thapsigargin, an inhibitor of endoplasmic reticulum Ca2+ pumps,
      failed to prevent the InsP3-induced Ca2+ wave, suggesting that the generation of
      the Ca2+ wave is not attributed to the polarized distribution of the Ca2+ pumps.
      The photolysis of a high concentration (10 microM) of caged InsP3 caused a
      homogeneous increase in the fluorescence ratio throughout the cells, indicating
      that all regions of intracellular Ca2+ stores similarly responded to the high
      concentration of InsP3. The present study is the first demonstration of the InsP3
      induced Ca2+ wave in permeabilized exocrine acinar cells. The result provides
      fresh evidence that the apical region contains elements of intracellular Ca2+
      stores particularly sensitive to InsP3 and that the Ca2+ wave results from a
      polarized distribution of InsP3-sensitive Ca2+ stores.

PMID- 9620882
TI  - Transcript heterogeneity of the human reduced folate carrier results from the use
      of multiple promoters and variable splicing of alternative upstream exons.
AB  - We previously identified three separate cDNAs (KS6, KS32 and KS43) for the human
      reduced folate carrier (RFC) with unique 5' untranslated regions (5' UTRs) [Wong,
      Proefke, Bhushan and Matherly (1995) J. Biol. Chem. 270, 17468-17475]. Multiple
      RFC transcripts were confirmed in CCRF-CEM cells and transport-up-regulated
      K562.4CF cells by 5' rapid amplification of cDNA ends (5' RACE) and/or primer
      extension analysis. Two groups of 5' RACE clones were identified, one containing
      a variable length sequence identical with the KS43 cDNA 5' UTR, and another
      consisting of variants of the KS32 5' UTR, apparently generated by alternative
      splicing. The 5' UTR for the KS6 cDNA was not detected. A single band was
      detected on Southern blots of CCRF-CEM genomic DNA probed with a 326 bp genomic
      fragment common to all three cDNA species. The unique 5' UTRs for the KS43 and
      KS32 transcripts were localized to separate non-coding exons (exons 1 and 2
      respectively), upstream from a large (approx. 3.42 kb) intron; the KS6 5'UTR also
      mapped to exon 1. Exons 1 and 2 were contiguous with 996 and 342 bp GC-rich 5'
      flanking regions (designated Pro43 and Pro32 respectively) that contained
      multiple SP1 and AP2 but no TATA or CAAT boxes. Both Pro43 and Pro32 exhibited
      strong promoter activities when cloned in front of a luciferase reporter gene and
      transfected into HT1080 and K562 cells. By an analysis of promoter deletion
      mutants we identified two 89 bp tandem repeats that seemed to increase Pro32
      activity, and a 240 bp distal sequence that repressed Pro43 activity. Taken
      together, our results show that multiple human RFC transcripts are encoded by a
      single gene locus and that the heterogeneous 5' UTRs result from multiple
      transcriptional starts and variable splicing of alternative non-coding exons
      transcribed from separate promoters.

PMID- 9620883
TI  - G-Protein binding domains of the angiotensin II AT1A receptors mapped with
      synthetic peptides selected from the receptor sequence.
AB  - The vascular angiotensin II type 1 receptor (AT1AR) is a member of the G-protein
      coupled receptor superfamily. We mapped the G-protein binding domains of the
      AT1AR using synthetic peptides selected from the receptor sequence, which
      interfere with AT1AR-G-protein coupling. Membrane GTPase activity was used as a
      measure of the functional coupling in rat vascular smooth muscle cells. Peptides
      corresponding to the N-terminal region of the second intracellular loop (residues
      125-137), the N-terminal region of the third intracellular loop (217-227) and the
      juxtamembranous region of the C-terminal tail (304-316) inhibited angiotensin II
      induced GTPase activation by 30%, 30%, and 70%, respectively. The latter two
      domains (217-227 and 304-316) are predicted to form amphiphilic alpha-helices.
      Only the peptide representing residues 217-227 stimulated basal activity (45%).
      No synthetic peptide had a significant effect on either the number or the
      affinity of the AT1AR binding. These observations indicate that domains of the
      second and third regions and the cytoplasmic tail of the AT1AR interact with G
      proteins, and that multiple contacts with these receptor domains may be important
      for binding and activation of the G-proteins.

PMID- 9620884
TI  - Human alpha-galactosidase A: glycosylation site 3 is essential for enzyme
      solubility.
AB  - Human alpha-galactosidase A (EC 3.2.1.22; alpha-Gal A) is the homodimeric
      glycoprotein that hydrolyses the terminal alpha-galactosyl moieties from
      glycolipids and glycoproteins. The type, site occupancy and function of the N
      linked oligosaccharide chains on this lysosomal hydrolase were determined.
      Endoglycosidase treatment of the purified recombinant enzyme and mutagenesis
      studies indicated that three (Asn-139, Asn-192 and Asn-215) of the four potential
      N-glycosylation consensus sequences were occupied by complex, high-mannose and
      hybrid-type oligosaccharides respectively. When expressed in COS-1 cells,
      glycoforms with glycosylation site 1 or 2 obliterated had more than 70% of wild
      type activity, and both glycoforms were secreted. In contrast, the glycoform with
      only site 3 eliminated had decreased activity (less than 40%); little, if any,
      was secreted. Expressed mutant glycoforms in which site 3 and site 1 or 2 were
      obliterated had little, if any, intracellular or secreted enzymic activity, and
      immunofluorescence microscopy revealed that the expressed mutant glycoforms were
      retained in the endoplasmic reticulum, presumably where they were degraded. Thus
      glycosylation at site 3 was crucial to the formation of soluble, active enzyme,
      as well as transport to the lysosome. Absence of the site 3 hybrid-type
      oligosaccharide exposed an adjacent, normally protected, hydrophobic region,
      resulting in aggregation of the enzyme polypeptide in the endoplasmic reticulum.
      In support of this concept, endoglycosidase H-treated enzyme or mannose
      terminated enzyme expressed in Autographa californica cells also aggregated when
      concentrated, emphasizing that site 3 occupancy by a hybrid-type oligosaccharide
      was required for enzyme solubility.

PMID- 9620886
TI  - Purification and kinetic analysis of a baculovirus ecdysteroid UDP
      glucosyltransferase 

PMID- 9620887
TI  - Human immunodeficiency virus and hepatitis C virus coinfection.
AB  - Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) share the same
      parenteral, sexual and vertical routes of transmission (McNair et al. 1992). This
      common epidemiology explains the high frequency of combined infections by
      hepatotropic viruses in HIV-infected patients. The aim of the present review is
      to clarify some important issues dealing with the reciprocal interactions between
      HIV and hepatitis C virus infections. The main topics include epidemiology,
      virological markers of HIV-infection, histopathology, natural course and
      treatment of hepatitis C in HIV-infected individuals.

PMID- 9620885
TI  - ATP-dependent transport of glutathione conjugate of 7beta, 8alpha-dihydroxy
      9alpha,10alpha-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene in murine hepatic
      canalicular plasma membrane vesicles.
AB  - Glutathione (GSH) S-transferases (GSTs) have an important role in the
      detoxification of (+)-anti-7,8-dihydroxy-9,10-oxy-7,8,9, 10
      tetrahydrobenzo[a]pyrene [(+)-anti-BPDE], which is the ultimate carcinogen of
      benzo[a]pyrene. However, the fate and/or biological activity of the GSH conjugate
      of (+)-anti-BPDE [(-)-anti-BPD-SG] is not known. We now report that (-)-anti-BPD
      SG is a competitive inhibitor (Ki 19 microM) of Pi-class isoenzyme mGSTP1-1,
      which among murine hepatic GSTs is most efficient in the GSH conjugation of (+)
      anti-BPDE. Thus the inhibition of mGSTP1-1 activity by (-)-anti-BPD-SG might
      interfere with the GST-catalysed GSH conjugation of (+)-anti-BPDE unless one or
      more mechanisms exist for the removal of the conjugate. The results of the
      present study indicate that (-)-anti-BPD-SG is transported across canalicular
      liver plasma membrane (cLPM) in an ATP-dependent manner. The ATP-dependent
      transport of (-)-anti-[3H]BPD-SG followed Michaelis-Menten kinetics (Km 46
      microM). The ATP dependence of the (-)-anti-BPD-SG transport was confirmed by
      measuring the stimulation of ATP hydrolysis (ATPase activity) by the conjugate in
      the presence of cLPM protein, which also followed Michaelis-Menten kinetics. In
      contrast, a kinetic analysis of ATP-dependent uptake of the model conjugate S
      [3H](2,4-dinitrophenyl)-glutathione ([3H]DNP-SG) revealed the presence of a high
      affinity and a low-affinity transport system in mouse cLPM, with apparent Km
      values of 18 and 500 microM respectively. The ATP-dependent transport of (-)-anti
      BPD-SG was inhibited competitively by DNP-SG (Ki 1.65 microM). Likewise, (-)-anti
      BPD-SG was found to be a potent competitive inhibitor of the high-affinity
      component of DNP-SG transport (Ki 6.3 microM). Our results suggest that GST
      catalysed conjugation of (+)-anti-BPDE with GSH, coupled with ATP-dependent
      transport of the resultant conjugate across cLPM, might be the ultimate
      detoxification pathway for this carcinogen.

PMID- 9620888
TI  - Blue toe syndrome after initiation of low-dose oral anticoagulation.
AB  - Cholesterol emboli are a known complication after arterial catheterization,
      arterial surgery, and after lysis with plasminogen activators. The clinical
      presentation of cholesterol emboli is variable ranging from a localized blue toe
      syndrome to a multisystem disease. The purpose of this case report is to report
      on a patient with blue toe syndrome and livedo reticularis occuring two months
      after initiation of low-dose oral anticoagulation with phenproucomon. The non
      invasive studies revealed an infrarenal abdominal aneurysma lined by a thin wall
      thrombus as a potential source of cholesterol emboli. The patient had a benign
      course with resolution of toe pain after a period of four weeks, without
      development of an ulceration. The case report demonstrates that cholesterol
      emboli may also occur in patients treated with low-dose oral anticoagulation and
      no previous arterial catheterization.

PMID- 9620889
TI  - Tenascin is a useful marker in the diagnosis of inflammatory myopathies.
AB  - The expression of tenascin, NCAM, vimentin and HSP-70 was examined in 15 patients
      with dermatomyositis and 12 patients with polymyositis. All biopsies with
      dermatomyositis showed a confluent network of tenascin expression in the
      extracellular space. This network surrounded numerous fibers (39 up to 320).
      Tenascin expression preceded other histological and immunohistochemical signs of
      dermatomyositis such as the expression of N-CAM and vimentin and the appearance
      of perifascicular atrophy and inflammatory response. Tenascin expression was
      found in 3 biopsies where microtubular inclusions in the arteriolar walls were
      absent. In contrast, tenascin expression was confined to the surroundings of
      necrotic fibers also expressing vimentin or N-CAM in polymyositis. In general,
      tenascin was found in the vicinity of inflammatory cells, only. These findings
      suggest that tenascin is induced by ischemic stress in dermatomyositis.
      Widespread tenascin expression in a fascicular distribution is a specific marker,
      if an inflammatory myopathy has been proven by standard techniques. In some
      cases, tenascin staining might confirm the clinical diagnosis of dermatomyositis,
      where other histological findings are inconclusive.

PMID- 9620890
TI  - Soluble intercellular adhesion molecule 1 (sICAM-1) in bronchoalveolar lavage
      (BAL) cell cultures and in the circulation of patients with tuberculosis,
      hypersensitivity pneumonitis and sarcoidosis.
AB  - Intercellular adhesion molecule-1 (ICAM-1) plays an important role in
      inflammatory diseases. It is believed that its soluble form (sICAM-1) might be a
      serum parameter of inflammatory activity with possible relevance in granulomatous
      disorders. To evaluate this role we measured sICAM-1 by ELISA in serum and
      shedding of this molecule by BAL cells in patients with granulomatous lung
      diseases (pulmonary tuberculosis (TB), hypersensitivity pneumonitis (HSP),
      pulmonary sarcoidosis (PS), and controls). Serum concentrations of sICAM-1 in
      patients with TB (496.9 +/- 49.7 ng/ml), with HSP (636.5 +/- 85.9.8 ng/ml), and
      with PS (588.3 +/- 72.2 ng/ml) were significantly increased compared to controls
      (275.7 +/- 33.1 ng/ml). Spontaneous release of sICAM-1 by BAL cells differed
      among patient groups (TB: 9.3 +/- 1.7; HSP: 17.5 +/- 1.4; PS: 9.7 +/- 1.5 ng/ml),
      however, exceeding that of controls significantly (3.8 +/- 0.6 ng/ml). No
      correlations between the circulating level and the shedding of this molecule by
      BAL cells were observed within the groups. Significant correlations between serum
      sICAM-1 and serum tumor necrosis factor alpha (TNFalpha) level were observed in
      patients with HSP and TB. Kinetic cell culture experiments with BAL cells
      revealed a dissociation in sICAM-1 shedding and TNFalpha release. After
      stimulation rapid upregulation of both molecules (5 h) was followed by a
      cessation of TNFalpha production at 28 h. sICAM-1 shedding, however, was
      maintained over 2 days. Our results evidence that the circulating pool of sICAM
      1, as well as the shedding of this molecule by BAL cells reflect the activity of
      cells in the inflammatory processes of granulomatous diseases.

PMID- 9620891
TI  - Fructose malabsorption is associated with early signs of mental depression.
AB  - Fructose malabsorption is characterized by the inability to absorb fructose
      efficiently. As a consequence fructose reaches the colon were it is broken down
      by bacteria to short fatty acids, CO2 and H2. Bloating, cramps, osmotic diarrhea
      and other symptoms of irritable bowel syndrome are the consequence and can be
      seen in about 50% of fructose malabsorbers. Having made the observation that
      persons with fructose malabsorption very often seem to present not only with
      signs of irritable bowel syndrome but also with signs of pre-menstrual syndrome
      and mental depression, it was of interest to establish whether such an
      association could be demonstrated in patients. Fifty-five adults with
      gastrointestinal complaints of unknown origin (12 males, 43 females) were
      analyzed by measuring breath hydrogen concentrations after an oral dose of 50 g
      fructose and were classified as normals or fructose malabsorbers according to
      their breath H2 concentrations. All patients filled out a Beck s depression
      inventory - questionnaire. Fructose malabsorption was detected in 36 of 55
      individuals (65.5%). Subjects with fructose malabsorption (DeltaH2 concentrations
      >10 p.p.m. after fructose load) showed a significantly higher score in the Beck s
      depression inventory than normal fructose absorbers. This was true especially for
      females. Fructose malabsorption may play a role in the development of depressed
      mood. Fructose malabsorption should be considered in patients with symptoms of
      major depression or pre-menstrual syndrome. Further studies are needed to clarify
      the background of this association.

PMID- 9620892
TI  - Recombinant human interleukin-10 attenuates TNFalpha production by porcine
      monocytes.
AB  - BACKGROUND: Human recombinant interleukin-10 (rhIL-10) has been found to inhibit
      endotoxin-induced production of several proinflammatory cytokines including tumor
      necrosis factor alpha (TNFalpha) from human monocytes. The exogenous therapeutic
      administration of rhIL-10 in acute and chronic hyperinflammatory conditions has
      been discussed. For none of the large animal species that have been used to study
      the role and effects of various mediators during septicemia, crossreactivity of
      rhIL-10 has been shown so far. Therefore, the aim of the present investigation
      was to evaluate the crossreactivity of rhIL-10 in a porcine model. METHODS: To
      determine the effects of rhIL-10 on endotoxin-challenged porcine monocytes, we
      incubated porcine peripheral blood monocytes from five donors with three
      different concentrations of rhIL-10 (500 ng/ml, 1000 ng/ml and 2000 ng/ml,
      respectively) either simultaneously with, or two hours prior to
      lipopolysaccharide (LPS) administration. RESULTS: As compared to incubation with
      LPS (1 microg/ml) alone, coincubation with LPS and rhIL-10 (500 ng/ml, 1000 ng/ml
      and 2000 ng/ml) (n = 5) for four hours resulted in a marked and uniform reduction
      of immunoreactive TNFalpha. For preincubation (n = 5), only the addition of 500
      ng/ml rhIL-10 led to a homogeneous decrease of TNFalpha levels in each sample.
      There was no consistent reduction in TNFalpha after preincubation with 1000 and
      2000 ng/ml rhIL-10. Our results indicate crossreactivity of recombinant human
      interleukin-10 in porcine peripheral blood monocytes. Further investigations on
      the potential therapeutical role of exogenously administered rhIL-10 are thus
      possible in porcine models.

PMID- 9620893
TI  - POEMS syndrome with vascular lesions and renal carcinoma - possible role of
      cytokines.
AB  - We describe here the case of a 60 years man with POEMS syndrome associated with
      renal tumor and vascular lesions. The patient had osteosclerotic myeloma IgA
      lambda, polyneuropathy, endocrinopathy and skin changes. In addition, he
      developed renal clear cell carcinoma and gangrena of lower limbs. The humoral
      study showed thrombocytosis, high levels of IL-1beta and IL-6 and of some
      coagulative/fibrinolytic and endothelial factors (von Willebrand factor, plasmin
      antiplasmine complexes, plasminogen activator). We suggest the hypothesis that
      these factors are capable of determining some manifestations of POEMS syndrome.

PMID- 9620894
TI  - Modulation of cellular and humoral immune responses during exposure of healthy
      individuals to an aqueous mistletoe extract.
AB  - Mistletoe extracts have been shown to exert immunomodulatory properties. However,
      little is known about changes in different immunological parameters during
      therapy. Aim of our study was, therefore, to investigate the influence of
      subcutaneous treatment in 8 volunteers who were exposed to an aqueous mistletoe
      extract (Viscum album Mali; VM) for 8 weeks. During in vivo exposure, VM induced
      the production of anti-ML-1 antibodies of the IgG-type. A pronounced
      proliferation of peripheral blood mononuclear cells (PBMC) could be observed in 6
      volunteers. However, the activity and time of maximal response varied from one
      individual to the other. There was no correlation between the cellular and the
      humoral reactivity and different antigens present in this mistletoe extract may
      be operative at different levels of the immune system. In order to define more
      precisely the type of immune response, cytokines were measured in the
      supernatants of VM-stimulated cell cultures. VM induced the secretion of Th1-
      (IFN-gamma) or Th2- (IL-4) related cytokines and also the release of TNF-alpha
      and IL-6. All these different immunological phenomena can be best explained by
      presentation of mistletoe-related antigens to T- and B-cells via antigen
      presenting cells in the draining lymph nodes.

PMID- 9620895
TI  - New tuberculosis drug development. How can we do better?

PMID- 9620896
TI  - Virus-induced airway hyperresponsiveness and asthma.

PMID- 9620897
TI  - Multiple system organ failure. Is mechanical ventilation a contributing factor?

PMID- 9620898
TI  - Rifapentine and isoniazid in the continuation phase of treating pulmonary
      tuberculosis. Initial report.
AB  - A randomized comparison has been made of three times weekly rifampin plus
      isoniazid (HR3) with rifapentine plus isoniazid given once weekly (HRp1) or on 2
      of 3 wk (HRp1.2/3) in the continuation phase of 6-mo regimens (each starting with
      an initial 2 mo of 4-drug therapy) for the treatment of pulmonary tuberculosis in
      672 Chinese patients in Hong Kong. Because of poor bioavailability of the
      rifapentine used (produced in China), its dose size was increased from 600 mg
      initially to about 750 mg in the last third of patients to obtain serum
      concentrations similar to those with rifapentine of Western origin; all doses
      were given after a meal promoting absorption. After initial exclusions, an intent
      to treat analysis, done on the remaining 592 patients, showed 45 adverse
      treatment events in 7 of 190 HR3 patients, in 17 of 199 HRp1 patients, and in 21
      of 203 HRp1.2/3 patients; of these, 42 were bacteriological or radiographic
      relapses after the end of treatment (HR3 versus HRp1, p = 0.04; HR3 versus
      HRp1.2/3, p = 0.01). Patients with organisms initially sensitive or resistant to
      isoniazid or streptomycin had similar relapse rates. The high relapse rate in the
      HRp1 regimen suggests that the rifapentine dose should be increased. Similarity
      of relapse rates, 8.9% and 10.4%, after the HRp1 and HRp1.2/3 regimens,
      respectively, indicates that irregularity in taking rifapentine/isoniazid could
      be tolerated. The few adverse side effects in the continuation phase in the
      rifapentine regimens were less frequent than in the HR3 regimen.

PMID- 9620899
TI  - Characterization of obstructive airway disease in family members of probands with
      asthma. An algorithm for the diagnosis of asthma.
AB  - To investigate the genetic susceptibility to asthma, we developed an algorithm to
      classify the phenotype of each family member enrolled in a family study on the
      genetics of asthma. This algorithm was applied to 92, two- and three-generation
      families, identified through a subject (proband) with asthma first diagnosed 25
      yr previously. The algorithm consisted of five classes based on the presence or
      absence of bronchial hyperresponsiveness (BHR), respiratory symptoms, smoking,
      airways obstruction, and bronchodilator reversibility. All family members were
      classified as: (1) definite asthma; (2) probable asthma; (3) unclassifiable
      airway disease; (4) chronic obstructive pulmonary disease (COPD); (5) unaffected
      (without clinical evidence of asthma and COPD). Thirteen of the 92 probands (14%)
      could not be classified as asthmatic when retested 25 yr later because of loss of
      BHR, loss of bronchodilator reversibility, or a current history of cigarette
      smoking. Of the 265 first-degree offspring, 49 (18%) were classified as having
      definite asthma (Class 1), and 22 (8%) as probable asthma (Class 2). A large
      number of offspring with clinical evidence of asthma did not have a prior
      physician's diagnosis of asthma, and offspring in Class 1 (definite asthma), with
      and without a physician's diagnosis, had similar clinical and physiologic
      characteristics. These results support the usefulness of this approach to
      classify subjects with asthma for genetic epidemiologic studies and show that
      reliance on a prior physician's diagnosis may result in misclassification or
      underdiagnosis. Characterization of the offspring in this family study showed
      that there is familial clustering, which supports the presence of a hereditary
      component in asthma.

PMID- 9620900
TI  - Cardiopulmonary effects of aerosolized prostaglandin E1 and nitric oxide
      inhalation in patients with acute respiratory distress syndrome.
AB  - Ten patients with acute respiratory distress syndrome (ARDS) received in random
      order nitric oxide (NO) inhalation, aerosolized prostaglandin E1 (PGE1), infusion
      of PGE1, or no intervention. Inhalation of either aerosolized PGE1 (10 +/- 1
      ng/kg/min) or NO (7 +/- 1 ppm) reduced pulmonary vascular resistance (PVR) from
      158 +/- 14 to 95 +/- 11 dyn . s/cm5/m2 (NO) and 100 +/- 12 dyn . s/cm5/m2
      (aerosolized PGE1), and improved PaO2 from 78 +/- 3 to 96 +/- 5 mm Hg (NO) and 95
      +/- 4 mm Hg (aerosolized PGE1) (p < 0.05), venous admixture (Q VA/Q T) from 45 +/
      2 to 36 +/- 2% (NO), and 36 +/- 2% (aerosolized PGE1) (p < 0.05), oxygen
      delivery (DO2) from 711 +/- 34 to 762 +/- 45 ml/min/m2 (NO) and 780 +/- 46
      ml/min/m2 (aerosolized PGE1) (p < 0.05), and right ventricular ejection fraction
      (RVEF) from 32 +/- 6 to 37 +/- 5% (NO), and 36 +/- 4% (aerosolized PGE1) (p <
      0.05) at a constant cardiac index (CI). Although infusion of PGE1 (12 +/- 1
      ng/kg/min) caused a similar reduction in PVR as aerosolized PGE1 and NO
      inhalation, it improved RVEF and increased CI but decreased Q VA/Q T and PaO2.
      These results suggest that in ARDS patients inhalation of aerosolized PGE1 or NO
      in low concentrations equally improves PVR and gas exchange by selective
      vasodilation in ventilated areas.

PMID- 9620901
TI  - Intranasal cold dry air is superior to histamine challenge in determining the
      presence and degree of nasal hyperreactivity in nonallergic noninfectious
      perennial rhinitis.
AB  - The objective of the study was to compare cold dry air (CDA) and histamine in
      differentiating patients with nonallergic noninfectious perennial rhinitis
      (NANIPER) from control subjects. Nasal reactivity (nasal patency, mucus
      production, and sneezing) in 16 symptomatic nonsmoking patients with NANIPER and
      seven nonsmoking control subjects was measured with standardized CDA and
      histamine provocation series in a randomized crossover study. Intranasal CDA
      resulted in increased mucus production and nasal blockage in a dose-dependent
      manner in patients with NANIPER but not in control subjects. Sneezing did not
      occur. The reproducibility of CDA for patency and mucus production was good.
      Sensitivity for CDA was 87% compared with 100% for histamine. However,
      specificity was 71% for CDA and 0% for histamine. It is concluded that the new
      standardized intranasal CDA provocation method uses a recognizable natural
      nonspecific stimulus and seems to be more suitable than histamine for
      characterizing and assessing the presence and degree of nasal reactivity in
      NANIPER.

PMID- 9620902
TI  - Effect of resistive loading on variational activity of breathing.
AB  - To examine the effect of resistive loading on variational activity of breathing,
      we studied 18 healthy subjects breathing at rest and with inspiratory resistive
      loads of 3 and 6 cm H2O/L/s, applied randomly for 1 h each. Compared with resting
      breathing, a resistive load of 3 cm H2O/L/s decreased the total variational
      activity of expiratory time (TE) and minute ventilation (V I), whereas a load of
      6 cm H2O/L/s increased the total variational activity of inspiratory time (TI).
      Compared with the load of 3 cm H2O/L/s, the load of 6 cm H2O/L/s increased total
      variational activity of tidal volume (VT), TI, TE, and V I. Partitioning of the
      total variational activity revealed that these alterations were due to changes in
      the random uncorrelated fraction. Compared with rest, both the resistive loads of
      3 and 6 cm H2O/L/s increased the number of breath lags displaying significant
      serial correlations ("short-term memory") of TI. Compared with rest, the load of
      3 cm H2O/L/s increased the autocorrelation coefficient at a lag of one breath for
      VT and the load of 6 cm H2O/L/s increased the correlated fraction of variational
      activity of VT. Thus, three measures of correlated behavior-autocorrelation
      coefficient at a lag of 1 breath, "short-term memory," and the correlated
      fraction of total variational activity- increased with loading. In conclusion,
      resistive loading changed total variational activity according to the size of the
      load: the random fraction decreased with the smaller load but increased with the
      larger load; in contrast, correlated behavior increased with both loads. The
      different behaviors of random and correlated variability with loading may reflect
      different physiologic influences on respiratory control.

PMID- 9620903
TI  - Circulating immunoreactive interleukin-6 in cystic fibrosis.
AB  - We measured circulating and sputum-sol concentrations of interleukin-6 (IL-6),
      tumor necrosis factor-alpha (TNF-alpha), neutrophil elastase-alpha1
      antiproteinase complex (NEAPC), and C-reactive protein (CRP) in an exacerbation,
      after antibiotic treatment, and in clinically stable patients with cystic
      fibrosis and chronic pulmonary infection with Pseudomonas aeruginosa. The aim was
      to determine the compartmental patterns of a proinflammatory and anti
      inflammatory cytokine compared with other markers of inflammatory activity in
      cystic fibrosis. IL-6, NEAPC, CRP, and absolute neutrophil count were reduced
      after antibiotic treatment, p < 0.01. IL-6 and CRP concentrations were greater, p
      = 0.007, and p = 0.01, respectively, in a stable group of patients compared with
      those at the end of an exacerbation. IL-6 and CRP concentrations were related (r
      = 0.836, p < 0.0001), and both were greater than in matched control subjects (p <
      0.001) at all times studied. Sputum-sol concentrations of IL-6 after treatment
      were positively related to FEV1 and FVC and inversely related to concentrations
      of neutrophil elastase. The separation between patients and healthy subjects, and
      the reduction of IL-6 after antibiotic treatment indicates it could be used as a
      marker of inflammation, but its relationship to other markers depends on the
      compartment in which it is measured.

PMID- 9620904
TI  - Genetic epidemiology of severe, early-onset chronic obstructive pulmonary
      disease. Risk to relatives for airflow obstruction and chronic bronchitis.
AB  - Severe alpha-1-antitrypsin deficiency is the only proven genetic risk factor for
      chronic obstructive pulmonary disease (COPD). We have assembled a cohort of 44
      probands with severe, early-onset COPD, who do not have severe alpha-1
      antitrypsin deficiency. A surprisingly high prevalence of females (79.6%) was
      found. Assessment of the risk to relatives of these early-onset COPD probands for
      airflow obstruction and chronic bronchitis was performed to determine whether
      significant familial aggregation for COPD, independent of alpha-1-antitrypsin
      deficiency, could be demonstrated. First- degree relatives of early-onset COPD
      probands had significantly lower FEV1 and FEV1/FVC values than control subjects
      (p < 0.01), despite similar pack-years of smoking. Reduced spirometric values in
      first-degree relatives of early-onset COPD probands were found only in current or
      ex-cigarette smokers. The mean FEV1 in current or ex-smoking first-degree
      relatives was 76.1 +/- 20.9% predicted compared to 89.2 +/- 14.4% predicted in
      current or ex-smoking control subjects (p < 0.01); in lifelong nonsmokers, the
      mean FEV1 was 93.4% predicted for both control subjects and first-degree
      relatives of early-onset COPD probands. Generalized estimating equations,
      adjusting for age and pack-years of smoking, demonstrated increased odds of
      reduced FEV1 and chronic bronchitis in current or ex-smoking first-degree
      relatives of early-onset COPD probands. Using a new method to estimate relative
      risk from relative odds, we estimate that the relative risks for FEV1 below 60%,
      FEV1 below 80%, and chronic bronchitis are each approximately three in current or
      ex-smoking first-degree relatives of early-onset COPD probands. The increased
      risk to relatives of early-onset COPD probands for reduced FEV1 and chronic
      bronchitis, limited to current or ex-smokers, suggests genetic risk factor(s) for
      COPD that are expressed in response to cigarette smoking.

PMID- 9620905
TI  - Improvement of cystic fibrosis airway mucus transportability by recombinant human
      DNase is related to changes in phospholipid profile.
AB  - The aim of this study was to test whether changes in mucus surface properties by
      rhDNase treatment could be related to an increased recovery of phospholipids.
      Purulent sputa from 18 patients with cystic fibrosis (CF) were incubated with
      either rhDNase (4 microg/ml) or control excipient. The incubation of mucus
      samples with rhDNase induced a significant increase (p < 0.002) in the sol phase
      proportion (33.7 +/- 24.0%) compared with that obtained with excipient (12.6 +/-
      12.4%). Phospholipids were recovered in significantly (p < 0.05) greater amounts
      from both mucus gel and sol phases after incubation with rhDNase. The
      phosphatidylglycerol content of mucus sol phase was significantly increased by
      rhDNase (p < 0.03), as well as the mucus gel phase surface properties and
      transport by ciliary activity and by cough (p < 0.05). The improvement of mucus
      gel surface properties and transport capacity by ciliary activity were
      significantly related to the increased recovery of phosphatidylglycerol (r = 
      0.74, p < 0.03 and r = 0.94, p < 0.05, respectively). These results suggest that
      rhDNase is able to increase the free water content and alter the phospholipid
      profile of mucus, with a related improvement in CF mucus transportability.

PMID- 9620906
TI  - Pulmonary gas exchange improves in the prone position with abdominal distension.
AB  - Arterial blood oxygenation in patients with adult respiratory distress syndrome
      is often improved in the prone position. Critically ill patients often have
      abdominal distension and whether similar improvements in gas exchange occur with
      the prone position is not known. We therefore studied the effect of posture on
      gas exchange in eight ketamine-anesthetized pigs with abdominal distension. A
      rubber balloon, placed in the abdominal cavity, was filled with water to increase
      intra-abdominal pressure. The animals were mechanically ventilated with FIO2 =
      0.4, and PaCO2 was kept constant. Gas exchange was measured in the supine and
      prone positions, with and without abdominal distension, in random order, using
      the multiple inert gas elimination technique (MIGET). When the abdomen was
      normal, the prone position increased PaO2 by 16 +/- 21 mm Hg (p < 0.05),
      accompanied by a small, but statistically insignificant, decrease in AaPO2 (p =
      0.08) and no change in ventilation/perfusion (V A/Q) heterogeneity measured by
      MIGET. In the presence of abdominal distension, the prone position increased Pa
      O2 by 26 +/- 18 mm Hg (p < 0.01) and decreased AaPO2 (p < 0.05) and V A/Q
      heterogeneity as measured by the log standard deviation of the perfusion
      distribution (p < 0.01) and the arterial-alveolar difference area (p < 0.05). In
      addition, intragastric pressure was lower in the prone position (p < 0.01). We
      conclude that in anesthetized, mechanically ventilated pigs, the prone position
      improves pulmonary gas exchange to a greater degree in the presence of abdominal
      distension than when the abdomen is normal.

PMID- 9620907
TI  - Weight loss is a reversible factor in the prognosis of chronic obstructive
      pulmonary disease.
AB  - The objective of the study was to further unravel the prognostic significance of
      body weight changes in patients with COPD. Two survival analyses were performed:
      (1) a retrospective study, including 400 patients with COPD none of whom had
      received nutritional therapy; (2) a post hoc analysis of a prospective study,
      including 203 patients with COPD who had participated in a randomized placebo
      controlled trial. There was no overlap between the patient groups. Baseline
      characteristics of all patients were collected on admission to a pulmonary
      rehabilitation center in stable clinical condition. In the prospective randomized
      placebo-controlled trial, the physiologic effects of nutritional therapy alone (n
      = 71) or in combination with anabolic steroid treatment (n = 67) after 8 wk was
      studied in patients with COPD prestratified into a depleted group and a
      nondepleted group. Mortality was assessed as overall mortality. The Cox
      proportional hazards model was used to quantify the relationship between the
      baseline variables age, sex, spirometry, arterial blood gases, body mass index
      (BMI), smoking, and subsequent overall mortality. Additionally, the influence of
      treatment response on mortality was investigated in the prospective study. The
      retrospective study revealed that low BMI (p < 0.001), age (p < 0.0001) and low
      PaO2 (p < 0.05) were significant independent predictors of increased mortality.
      After stratification of the group into BMI quintiles a threshold value of 25
      kg/m2 was identified below which the mortality risk was clearly increased. In the
      prospective study, weight gain (> 2 kg/8 wk) in depleted and nondepleted patients
      with COPD, as well as increase in maximal inspiratory mouth pressure during the 8
      wk treatment, were significant predictors of survival. On Cox regression analysis
      weight change entered as a time-dependent covariate remained an independent
      predictor of mortality in addition to all variables that were entered in the
      retrospective study. The combined results of the two survival analyses provide
      evidence to support the hypothesis that body weight has an independent effect on
      survival in COPD. Moreover the negative effect of low body weight can be reversed
      by appropriate therapy in some of the patients with COPD.

PMID- 9620908
TI  - Airways inflammation and glucan in a rowhouse area.
AB  - A study was undertaken in a number of rowhouses, some of which had had previous
      problems related to dampness and water leakage. The aim of the study was to
      assess the relation between exposure to airborne (1--> 3)-beta-D-glucan, a cell
      wall substance in molds, and airways inflammation. The study involved 75 houses
      with indoor (1--> 3)-beta-D-glucan levels ranging from 0 to 19 ng/m3. Of 170
      invited tenants, 129 (76%) participated in the study. A questionnaire relating to
      symptoms was used, and measurements were made of lung function and airway
      responsiveness. Myeloperoxidase (MPO), eosinophilic cationic protein (ECP), and C
      reactive protein (CRP) were measured in serum. Atopy was determined with the
      Phadiatop test. The major findings were a relation between exposure to (1--> 3)-
      beta-D-glucan and an increased prevalence of atopy, a slightly increased amount
      of MPO, and a decrease in FEV1 over the number of years lived in the house. The
      results suggests the hypothesis that exposure to (1--> 3)-beta-D-glucan or molds
      indoors could be associated with signs of a non-specific inflammation.

PMID- 9620909
TI  - Risk factors for near-fatal asthma. A case-control study in hospitalized patients
      with asthma.
AB  - We prospectively recruited patients admitted to the hospital with severe asthma
      to comprehensively evaluate the association of historical and physiologic
      features with the risk of near-fatal asthma (NFA). A case-control study design
      was used. All patients admitted with NFA (cases) were identified prospectively
      and compared with asthma patients admitted during the same period without
      respiratory failure (controls). Nineteen cases (age: 40.2 +/- 12.0 yr) (mean +/-
      SD) and 80 controls (age: 36 +/- 13.5 yr) were enrolled. Duration of asthma,
      gender, smoking status, ethnicity, and prevalence of atopy were similar in the
      case and control groups. More than 80% of patients in both groups reported
      worsening symptoms for more than 48 h before admission, and more than 50% were
      worse for longer than 7 d. There was no difference in degree of airways
      obstruction or bronchial hyperresponsiveness (PC20). Perception of dyspnea was
      similar in the cases and controls, but among cases the males had greater
      impairment than the females (Borg score: 1.9 +/- 1. 4 versus 3.9 +/- 1.2: p =
      0.05). Univariate analysis identified a history of previous mechanical
      ventilation (OR: 27.5; 95% CI: 6.60 to 113.7), admission to the intensive care
      unit (ICU) (OR: 9.9; 95% CI: 3.0 to 32.9), history of worse asthma during January
      and February (OR: 3.5; 95% CI: 1.0 to 11.8), and use of air-conditioning (OR:
      15.0; 95% CI: 1.3 to 166) as risk factors for NFA. Of concern was the dependence
      of most patients (59.8%) on the emergency department (ED) for initial care, and
      the small number of cases (16%) in which patients visited a physician before
      admission to the hospital. We have confirmed risk factors identified previously
      in retrospective studies of fatal and NFA, and have also shown that hospitalized
      patients with asthma, irrespective of severity of their asthma, share several
      characteristics, especially in terms of their failure to respond to worsening
      asthma.

PMID- 9620910
TI  - Adherence with twice-daily dosing of inhaled steroids. Socioeconomic and health
      belief differences.
AB  - Poor adherence to medication regimens may be contributing to the recent increase
      in asthma morbidity and mortality. We examined patient characteristics that may
      influence adherence to twice-daily inhaled steroid regimens. Fifty adults with
      moderate to severe asthma completed questionnaires examining sociodemographics,
      asthma severity, and health locus of control. Adherence was electronically
      monitored for 42 d. Following monitoring, patients' understanding of asthma
      pathophysiology and the function of inhaled corticosteroids were assessed.
      Patient beliefs about the effectiveness and convenience of these medications, and
      their perception of communications with their clinician were measured. Mean
      adherence was 63% +/- 38%; 54% of subjects recorded at least 70% of the
      prescribed number of inhaled-steroid actuations. Factors associated with poor
      adherence were less than 12 yr of formal education (p < 0. 001), poor patient
      clinician communication (p < 0.001), household income less than $20,000 (p =
      0.002), Spanish as primary language (p = 0.005), and minority status (p = 0.007).
      In a multiple logistic regression analysis, less than 12 yr of formal education
      (OR: 6.72; CI: 1.10 to 41.0) and poor patient-clinician communication (OR: 1.2;
      CI: 1.01 to 1.55) were independently associated with poor adherence. These
      results emphasize the importance of socioeconomic status and adequate patient
      clinician communication for adherence to inhaled-steroid schedules.

PMID- 9620911
TI  - Effect of inhaled interleukin-4 on airway hyperreactivity in asthmatics.
AB  - lnterleukin-4 (IL-4) has been shown to play a crucial role in the pathogenesis of
      allergic disease including bronchial asthma. In order to investigate the role of
      IL-4 in airway hyperreactivity, we investigated the effect of inhaled recombinant
      human IL-4 on airway responsiveness to methacholine and eosinophil numbers in
      induced sputum in eight patients with allergic asthma using a placebo-controlled
      study design. Our results demonstrated that in the control experiments receiving
      vehicle inhalation, methacholine PC20 values did not change nor did the numbers
      of eosinophils in sputum change from baseline values. In contrast, after IL-4
      inhalation, methacholine PC20 fell from baseline (0.43 +/- 1.81 mg/mI) to 0.22 +/
      1.73 mg/mI (p < 0.01) at 24 h, and to 0.21 +/- 1. 74 mg/ml (p < 0.01) at 48 h.
      Accompanying this increased airway sensitivity was a significant eosinophilia in
      sputum. Our data indicated that IL-4 increases airway responsiveness by
      recruiting eosinophils into the airway in patients with allergic bronchial
      asthma.

PMID- 9620912
TI  - Exhaled nitric oxide in human lung transplantation. A noninvasive marker of acute
      rejection.
AB  - Acute allograft rejection in animals and humans has been associated with
      increased nitric oxide production in the graft. Exhaled nitric oxide (ENO)
      measurement is a noninvasive method of assessing inflammation in airway diseases,
      e.g., asthma, which might be applicable to lung transplant recipients. Over 12
      months, ENO of lower respiratory origin was measured in 108 lung transplant
      recipients with a mean time after transplant of 1,083 d. ENO (mean +/- SEM; ppb)
      in stable patients (19.5 +/- 1.1; p < 0.001) was not different from that of
      healthy controls (23.8 +/- 3.2). ENO was significantly higher in episodes of
      clinical acute rejection (51.1 +/- 6.3) compared with stable patients but not
      elevated in bronchiolitis obliterans syndrome (18.6 +/- 1.5) or pulmonary
      infection (25.9 +/- 4.0). A retrospective analysis of bronchoscopy findings and
      concurrent ENO (n = 99) showed that ENO did not vary according to histological
      findings (normal, acute rejection grade I, nonspecific inflammatory change) or
      with a positive BAL culture. ENO was not correlated with differential lymphocyte
      and neutrophil counts. ENO appears to be a valid marker of clinical acute
      rejection in human lung transplantation as distinct from infection or
      bronchiolitis obliterans. Furthermore, bronchoscopic findings in the absence of a
      clinical illness were not associated with a rise in ENO.

PMID- 9620913
TI  - Improvement of survival in patients with diffuse panbronchiolitis treated with
      low-dose erythromycin.
AB  - Diffuse panbronchiolitis (DPB) is a chronic inflammatory disease of the airways
      with a high rate of mortality despite treatment with a combination of antibiotics
      and the use of supportive therapy such as oxygen administration. Low-dose
      erythromycin therapy (EM) (400 to 600 mg/d) has been found to improve the
      survival of patients with DPB, and most patients with DPB in Japan have been
      treated with this erythromycin regime since 1984. The purpose of this study was
      to evaluate the effects of treatment with erythromycin on the survival rate of
      patients with DPB in Japan. We compared the survival rates of 498 patients with
      DPB after dividing them into three groups according to the date of their first
      medical examination (Group a: 1970-1979, Group b: 1980-1984, Group c: 1985-1990).
      DPB had been diagnosed in these patients using the criteria of the Ministry of
      the Health and Welfare Diffuse Lung Disease Committee (MHW-DLDC), which includes
      chronic productive cough, shortness of breath, presence of roentgenologically
      smoldering symmetrical granular shadows in the middle and lower lung fields,
      limitation of airflow without decrease in DLCO, elevated serum cold hemagglutinin
      titers, and/or narrowing bronchiolus with infiltration of lymphocytes and foamy
      alveolar macrophages. These patients were registered in the DPB research group of
      the Ministry of Health and Welfare (MHW). Survival rates were statistically
      compared using the generalized-Wilcoxon test. The survival rate of Group c was
      significantly higher than that of Groups a (p < 0.0001) and b (p < 0. 0001). In
      Group c, eight of 87 patients died; five died in the EM nontreated subgroup (n =
      24), and three died in the EM-treated subgroup (n = 63). There was a significant
      difference in the survival rates between the two subgroups in Group c (p <
      0.001). Treatment with EM was associated with a significant improvement in the
      rate of survival of patients with DPB. The efficacy of EM treatment increased the
      survival rate of patients with DPB, which was more significant in the older than
      in the younger patients.

PMID- 9620914
TI  - Mismatches at the HLA-DR and HLA-B loci are risk factors for acute rejection
      after lung transplantation.
AB  - Early high-grade acute rejections (pathologic grade A2 or A3) in recipients of
      lung allografts are a major risk factor for the subsequent development of
      obliterative bronchiolitis (OB). We analyzed the risk factors for high-grade
      acute rejections in 152 recipients of single (100) or bilateral (52) lung
      allografts transplanted at our institution between 1990 and 1996. Using Kaplan
      Meier product limit estimate analysis, there was a 50% probability of grade A2 or
      A3 rejection by 1 yr after transplant. By univariate analysis, the only
      significant predictor of early high-grade rejections was the presence of one or
      more mismatches at the HLA-DR locus (p = 0.038). This association was confirmed
      using the Cox proportional hazards model for multivariable analysis, with HLA-DR
      locus mismatch being the only risk factor identified for high-grade rejection (p
      = 0.036). Using repeated rejection analysis, recipients with one or more matches
      at the HLA-DR locus had a lower cumulative rate of grade A2 or A3 rejections
      during the first year compared with recipients with no matches at the HLA-DR
      locus (0.73 versus 1.32). In addition, recipients with one or more HLA-B locus
      matches had a lower cumulative rate of grade A2 or A3 rejections in the first
      year than did recipients with no matches at the HLA-B locus (0.59 versus 1.30).
      These results indicate that mismatches between donors and recipients at the HLA
      DR and HLA-B loci are important risk factors for early high-grade rejections
      after lung transplantation. Immunosuppressive protocols that are more effective
      in preventing recipient T-cell activation by donor alloantigens are likely to
      reduce the rate of high-grade acute rejections in recipients of lung transplants,
      and may directly impact on the time to onset of OB.

PMID- 9620915
TI  - Sublingual capnometry for diagnosis and quantitation of circulatory shock.
AB  - We investigated sublingual tissue PCO2 during hemorrhagic and septic shock.
      Hemorrhagic shock was induced in 10 rats. Sublingual PCO2 increased from 45 to
      125 mm Hg and arterial pressure declined from 138 to 49 mm Hg, end-tidal PCO2
      decreased from 35 to 13 mm Hg, and cardiac index fell from 290 to 77 ml/min/kg.
      Arterial blood lactate increased from 0.9 to 15.8 mmol/L. Gastric PCO2 was
      measured in five animals and it increased from 46 to 87 mm Hg. No significant
      changes were observed in eight "sham" bled animals including the five animals in
      which gastric PCO2 was measured. Highly significant linear correlations (p <
      0.001) between sublingual PCO2 and gastric PCO2 (r = 0.71), cardiac index (r = 
      0.74), and arterial lactate (r = 0.59) were documented. We subsequently
      investigated sublingual PCO2 in five animals in which sepsis was induced by
      intravenous infusion of live Staphylococcus aureus. Like hemorrhagic shock,
      highly significant linear correlations were observed between end-tidal PCO2 and
      cardiac index and between sublingual PCO2 and arterial blood lactate. Sublingual
      PCO2 promises to serve as a technically simple, noninvasive, and rapid response
      quantitator of severity of circulatory shock states.

PMID- 9620916
TI  - Effects of topically delivered benzamil and amiloride on nasal potential
      difference in cystic fibrosis.
AB  - The raised nasal transepithelial potential difference (PD) in cystic fibrosis
      (CF) reflects accelerated active transport of Na+, and is inhibited by topical
      administration of the Na+ channel blocker, amiloride. The aim of this study was
      to investigate the dose-effect and time course of topically administered Na+
      conductance inhibitors to inhibit nasal PD, including benzamil, an analog of
      amiloride. We measured the magnitude of drug inhibition of Na+ transport [percent
      inhibition of baseline PD (DeltaPD%)] and duration of inhibition of PD, defined
      as the time when drug inhibition of PD had recovered by 50% (effective time =
      ET50). Amiloride [10(-)3 M (n = 16), 3 x 10(-)3 M (n = 9), 6 x 10(-)3 M (n = 7),
      10(-)2 M (n = 3)] or benzamil [1.7 x 10(-)3 M (n = 7), and 7 x 10(-)3 M (n = 5)]
      were administered to the nasal surface via an aerosol generated by a jet
      nebulizer and a nasal mask. The concentration-dependent magnitude (DeltaPD%) of
      inhibition was similar for amiloride and benzamil ( approximately 67- 77%),
      whereas the duration of inhibition (ET50) was about two-and-a-half times longer
      after benzamil administration as compared with equivalent concentrations of
      amiloride [1.6 +/- 0. 06 versus 4.5 +/- 0.6 h (ET50 +/- SEM), at 6-7 x 10(-)3 M].
      In vitro studies of cultured normal nasal epithelia demonstrated directly that
      benzamil induced an approximately 2-fold more prolonged inhibition of active Na+
      transport than amiloride. These data suggest aerosolized benzamil is a candidate
      long-duration Na+ channel blocker for CF.

PMID- 9620917
TI  - Protein C anticoagulant system in patients with interstitial lung disease.
AB  - Excessive procoagulant activity in the alveolar space may play a relevant role in
      the pathogenesis of pulmonary fibrosis. Hypercoagulability results from the
      disruption of the balance between the procoagulant and anticoagulant factors. The
      aim of this study was to assess the levels of molecular markers of the
      anticoagulant protein C (PC) pathway in the bronchoalveolar lavage fluid (BALF)
      and plasma of 11 patients with idiopathic pulmonary fibrosis (IPF), 14 with
      sarcoidosis and 16 with collagen vascular disease (CVD)-associated interstitial
      lung disease (CVD-ILD). Six healthy nonsmoking volunteers served as control
      subjects. BALF concentrations of the marker of clotting activation, thrombin-
      antithrombin III complex (TAT), in patients with sarcoidosis and CVD-ILD were
      significantly greater than those in control subjects. PC levels in BALF were
      markedly higher in patients with IPF (610 +/- 150 ng/ml), sarcoidosis (680 +/-
      170 ng/ml), and CVD-ILD (1,580 +/- 600 ng/ml) than in control subjects (230 +/-
      140 ng/ml). BALF concentrations of activated PC-PC inhibitor (APC-PCI) complex
      were significantly decreased in IPF (0.46 +/- 0.16 ng/ml), sarcoidosis (0. 43 +/-
      0.11 ng/ml), and CVD-ILD (0.50 +/- 0.15 ng/ml) patients as compared with control
      subjects (1.08 +/- 0.23 ng/ml). APC-PCI/PC ratios were significantly lower in
      patients with IPF (2.70 +/- 1.74 ng/microg), sarcoidosis (1.94 +/- 0.82
      ng/microg), and CVD-ILD (1.89 +/- 0.68 ng/microg) than in control subjects (15.91
      +/- 8.45 ng/microg). Plasma levels of APC- PCI and the APC-PCI/PC ratio were also
      significantly decreased in patients with CVD-ILD as compared with control
      subjects. Overall, these findings suggest that decreased PC activation with
      increased procoagulant activity occurs in patients with ILD.

PMID- 9620918
TI  - Flow-dependent positive airway pressure to maintain airway patency in sleep apnea
      hypopnea syndrome.
AB  - Airway obstruction in patients with sleep apnea-hypopnea syndrome (SAHS) is due
      to increased critical pressure (Pcrit) of the upper airway. The ideal nasal
      pressure (Pn) to maintain airway patency should consist of the constant term to
      account for Pcrit and a term (Rn . V) proportional to flow (V) to account for the
      dynamic pressure drop through nasal resistance (R n). Continuous positive airway
      pressure (CPAP) applied to avoid flow limitation results in a Pn greater than
      required over most of the breathing cycle. The aim was to assess a flow-dependent
      positive airway pressure (FDPAP) based on adapting Pn to the instantaneous flow:
      Pn = P0 + k . V. FDPAP was tested on collapsible airway models and its
      applicability was assessed in nine patients with SAHS during sleep. In models,
      FDPAP prevented flow limitation with lower mean P n and work of breathing than
      CPAP. In patients FDPAP allowed the patients to breathe normally with a mean Pn
      (6.6 +/- 1.2 cm H2O) systematically and significantly (p < 0.05, paired t test)
      lower than when applying CPAP (9.1 +/- 1.2 cm H2O). The results found in models
      and in patients suggest that adapting the applied nasal pressure to the
      instantaneous breathing flow may be of potential practical interest in SAHS.

PMID- 9620919
TI  - Occupation, asthma, and chronic respiratory symptoms in a community sample of
      older women.
AB  - We evaluated the role of occupational factors on the prevalence of self-reported
      asthma, chronic bronchitis, and asthma-like respiratory symptoms among women >=
      55 yr. Occupational history, smoking, and respiratory conditions were collected
      through an interviewer-administered questionnaire from 1,226 women. Lung function
      data from 820 subjects were used for group "validation" of the outcome variables.
      Significant associations were observed between the respiratory conditions and
      occupational groupings based on the longest occupation held. Artists, writers,
      decorators, and photographers (odds ratio [OR] = 3.1), and women in service
      occupations (OR = 2.4) had a significantly increased risk of asthma. The odds of
      asthma-like symptoms was significantly elevated among nurses and other
      nonphysician health workers (OR = 2.9), social workers (OR = 2.9), and homemakers
      (OR = 2.4). Exposure to dusts, gas, vapors, fumes, or sensitizers was associated
      with a significantly increased odds of asthma (OR = 1.8) and with a marginally
      significant increased odds of asthma-like symptoms (OR = 1.4). Smoking accounted
      for a large proportion of asthma and asthma-like conditions in this population
      (population attributable risk [PAR] = 40.5% and 35.0%, respectively); employment
      in occupations with a high probability of exposures to dusts, gas, vapors, fumes,
      or sensitizers also contributed significantly to the burden of asthma (PAR = 15.1
      to 20.0%) and asthma-like symptoms (PAR = 7.5 to 10.2%).

PMID- 9620920
TI  - Antituberculosis drug-induced hepatotoxicity. The role of hepatitis C virus and
      the human immunodeficiency virus.
AB  - Until recently it was thought that age greater than 35 yr was the main risk
      factor for the development of drug-induced hepatitis (DIH) in patients receiving
      antituberculosis therapy. We conducted a study to determine whether infection
      with either the hepatitis C virus or the human immunodeficiency virus (HIV) were
      significant risk factors for the development of DIH in patients receiving
      antituberculosis therapy. Our study consisted of two parts. In the first part,
      134 consecutive patients admitted for the treatment of tuberculosis (TB) were
      followed for the development of DIH. All of these patients were also screened for
      the presence of hepatitis C and HIV. In the second part of the study, those
      patients who were hepatitis C positive and who developed DIH on repeated
      reintroduction of the anti-TB drugs were offered a liver biopsy. If active
      inflammation, which may be suggestive of hepatitis C infection, was present on
      the biopsy specimen, treatment with alpha-interferon was begun and the anti-TB
      drugs were subsequently reintroduced. During the 18 mo of the study, 22 patients
      developed DIH. The relative risk of developing DIH if the patient was hepatitis C
      or HIV positive was fivefold and fourfold, respectively (p < 0.05). If a patient
      was coinfected with both hepatitis C and HIV the relative risk of developing DIH
      was increased 14.4-fold (p < 0.002). In the treatment part, four patients were
      treated with alpha-interferon, and all were able to undergo the reintroduction of
      anti-TB therapy without reoccurrence of DIH. Infection with hepatitis C and HIV
      are independent and additive risk factors for the development of DIH during TB
      therapy. The treatment of hepatitis C with alpha-interferon may allow the
      reintroduction of anti-TB agents in those who previously developed DIH when
      exposed to these drugs.

PMID- 9620921
TI  - The effect of sustained-release morphine on breathlessness and quality of life in
      severe chronic obstructive pulmonary disease.
AB  - Morphine has been proposed as a treatment for breathlessness in patients with
      severe chronic obstructive pulmonary disease (COPD), but there is uncertainty as
      to whether or not it is effective. Orally administered sustained-release morphine
      was compared with placebo in a randomized, double-blind, crossover trial with two
      6-wk treatment periods separated by a 2-wk washout period. The primary end point
      was quality of life measured using the Chronic Respiratory Disease Questionnaire
      (CRQ). Secondary end points included 6-min walk (6MW), distance, and
      breathlessness scores. Sixteen subjects with a mean age 70.7 yr, FEV1 of 0.6 L,
      and VC of 1.90 L were studied. There was no change in the total CRQ score with
      either treatment, but the score on the Mastery subscale was significantly worse
      with morphine (p = 0.02). The 6MW distance increased by 21 m from the beginning
      to the end of the placebo treatment period, but it decreased by 35 m with
      morphine (p = 0.04). There were no differences between treatments in
      breathlessness scored on daily diary cards or on the Dyspnea subscale of the CRQ.
      Almost all the subjects experienced adverse effects related to morphine.
      Sustained-release morphine was not a useful treatment for breathlessness in these
      patients with severe COPD.

PMID- 9620922
TI  - Risk factors for rifampin mono-resistant tuberculosis.
AB  - Use of rifampin is required for short-course treatment regimens for tuberculosis.
      Tuberculosis caused by isolates of M. tuberculosis with resistance to rifampin
      and susceptibility to isoniazid is unusual, but it has been recognized through
      surveillance. Patients with tuberculosis (cases) with rifampin mono-resistance
      were compared with HIV-matched controls with tuberculosis caused by a drug
      susceptible isolate. A total of 77 cases of rifampin mono-resistant tuberculosis
      were identified in this multicenter study. Three were determined to be laboratory
      contaminants, and 10 cases had an epidemiologic link to a case with rifampin mono
      resistant tuberculosis, suggesting primary acquisition of rifampin-resistant
      isolates. Of the remaining 64 cases and 126 controls, there was no difference
      between cases and controls with regard to age, sex, race, foreign birth,
      homelessness, or history of incarceration. Cases were more likely to have a
      history of prior tuberculosis than were controls. Of the 38 cases and 74 controls
      with HIV infection, there was no difference between cases and controls with
      regard to age, sex, race, foreign birth, homelessness, history of incarceration,
      or prior tuberculosis. Cases were more likely to have histories of diarrhea,
      rifabutin use, or antifungal therapy. Laboratory analysis of available isolates
      showed that there was no evidence of spread of a single clone of M. tuberculosis.
      Further studies are needed to identify the causes of the development of rifampin
      resistance in HIV-infected persons with tuberculosis and to develop strategies to
      prevent its emergence.

PMID- 9620923
TI  - The use of a neural network to detect upper airway obstruction caused by goiter.
AB  - Goiter is a common condition and can cause upper airway obstruction (UAO), which
      may be difficult to detect. We have studied maximal expiratory and inspiratory
      flow volume loops using a neural network to see if this offers a better way to
      identify patients with UAO. The flow-volume loops from 155 patients with goiter
      were assessed by a human expert and sorted into those with and without UAO. The
      reliability of this assessment was judged by using two observers who repeated the
      sorting 8 wk apart. A set of 46 patients with loops suggesting UAO and a set of
      51 patients with normal flow loops were taken from these 155, and the loops from
      a further 50 subjects with airflow limitation caused by chronic obstructive
      pulmonary disease were used for training and testing the neural network. Novel
      and standard indices were derived from the loops and used by the neural network.
      The kappa score for agreement between each of the observers and the original
      classification were 0.5 and 0.46, respectively, with the agreement between the
      observers at each reading of 0.58 and 0.68. The neural network found that a
      combination of four novel scores for flatness of the expiratory loop, the moment
      ratio, and the FEV1/PEF ratio was best at identifying UAO with a kappa score of
      0.81, a sensitivity of 88%, specificity of 94% and an accuracy of 92%. We
      conclude that a neural network using only six indices taken from the expiratory
      limb of a flow-volume loop was better than human experts at identifying flow
      loops with UAO.

PMID- 9620924
TI  - Bone mass and vitamin D deficiency in adults with advanced cystic fibrosis lung
      disease.
AB  - Osteoporosis and fractures are increasingly recognized in children and adults
      with cystic fibrosis. To investigate the prevalence and pathogenesis of
      osteoporosis and low bone mass in adults with advanced pulmonary disease due to
      cystic fibrosis, we examined the relationships between bone mineral density
      (BMD), anthropomorphic variables, pulmonary status, glucocorticoid therapy, and
      vitamin D concentrations. BMD of the lumbar spine, hip, and proximal radius was
      measured by dual energy X-ray absorptiometry in 30 white adults (16 women), age
      30 +/- 2 yr (mean +/- SEM). Compared with a normal control population, the
      patients had significantly reduced BMD at the lumbar spine (17 +/- 3%), total hip
      and femoral neck (24 +/- 3% and 20 +/- 4%, respectively). The radius was
      significantly less demineralized (4 +/- 2%; p <= 0.003) than the other sites.
      Moreover, only 21% of patients with cystic fibrosis had normal BMD (T score > 
      1.0) at the lumbar spine, 23% at the hip sites, and 39% at the radius. Age,
      weight, and body mass index (BMI) were most strongly correlated with bone mass,
      whereas glucocorticoid therapy and pulmonary function were not predictive.
      Despite oral vitamin D (400 to 800 IU daily), the mean serum 25-hydroxyvitamin D
      (25-OHD) concentration was at the low end of the normal range (16 +/- 2 ng/ml;
      normal 10 to 52 ng/ml); 8 of 20 patients (40%) had frankly low (<= 10 ng/ml)
      levels. BMD was significantly lower in patients with low 25-OHD concentrations at
      the lumbar spine (0.774 +/- 0.02 versus 0.913 +/- 0.04 g/cm2; p = 0.01) and total
      hip (0.648 +/- 0.04 versus 0.811 +/- 0.04 g/cm2; p = 0.01). Vertebral fractures
      were present in 19% of subjects and 41% had a confirmed history of previous
      fracture. In summary, osteoporosis, low bone mass, and fractures are common in
      adults with advanced cystic fibrosis lung disease. Despite oral supplements,
      vitamin D deficiency is also common and is associated with more severe
      demineralization at the lumbar spine and hip. We conclude that the widespread
      practice of oral supplementation with 400 to 800 units of vitamin D is
      ineffective in maintaining normal vitamin D stores in many patients with cystic
      fibrosis. To ensure adequacy of vitamin D stores, measurement of serum 25-OHD
      should be included in the routine management of patients with cystic fibrosis.

PMID- 9620925
TI  - Repeated aerosol exposure to small doses of allergen. A model for chronic
      allergic asthma.
AB  - To improve our understanding of the pathophysiology of chronic allergic asthma,
      we mimicked natural allergen exposure by giving tiny doses of dust-mite extract
      (equivalent to estimated daily exposure in a typical bedroom) in three weekly
      sessions for 4 wk. Nine mild asthmatic adults who were highly sensitive to dust
      mite allergen participated in the study. Serial assessments of bronchial
      reactivity by methacholine challenge, pulmonary function, symptoms, and
      bronchodilator requirements were obtained. Seven of nine subjects had a twofold
      or more (median: 6, range: 2.7 to 25) reduction (p = 0.008) in PC20, after which
      saline inhalations were substituted for dust-mite extract. Bronchial reactivity
      returned to normal within 2 to 3 wk after cessation of dust-mite inhalations in
      all but one subject. Predosing FEV1 dropped 10% over 4 wk of provocation (p =
      0.001) and 7 of 9 returned to prestudy level within 2 wk after dosing was
      stopped. Late-phase responses were seen in 6 of 9 subjects. We conclude that
      repeated aerosol exposure to dust-mite allergen in doses comparable to natural
      bedroom exposure is sufficient to adversely affect pulmonary function and
      bronchial hyperractivity in sensitized individuals. These changes are rapidly
      reversible. This low-dose provocational strategy provides an attractive model for
      the experimental study of allergic asthma. Arshad SH, Hamilton RG, Adkinson NF,
      Jr. Repeated aerosol exposure to small doses of allergen: a model for chronic
      allergic asthma.

PMID- 9620926
TI  - Expression of epidermal growth factor and epidermal growth factor receptor
      immunoreactivity in the asthmatic human airway.
AB  - Chronic airway inflammation, one of the pathophysiologic features of bronchial
      asthma, is suspected to be responsible for irreversible pathological changes of
      airways, called airway remodeling. To examine the mechanisms of airway remodeling
      in asthma, we investigated the expression of epidermal growth factor (EGF) and
      its receptor immunohistochemically in asthmatic human airways. Airway specimens
      from seven patients with asthma were obtained from autopsied and surgically
      resected lungs. Control specimens were obtained from lungs of eight subjects
      without asthma and other pulmonary complications at autopsy. We stained those
      specimens by the avidin-biotin-peroxidase complex (ABC) method with anti-human
      polyclonal EGF antibody and monoclonal EGF receptor antibodies. Three different
      portions of airways-large bronchi (about 1 cm in diameter), small bronchi (about
      3 mm in diameter), and peripheral airways (less than 2 mm in diameter)-were
      examined. The thickness of the bronchial smooth muscle and basement membrane was
      significantly greater in the asthmatic airways than in controls. Clear
      immunoreactivities of EGF were widely observed on bronchial epithelium, glands,
      and smooth muscle in asthmatic airways. In the controls, the bronchial epithelium
      and the bronchial glands partially expressed faint EGF immunoreactivity. For the
      EGF receptor, clear immunoreactivities were also observed on bronchial
      epithelium, glands, smooth muscle, and basement membrane in asthmatic airways. In
      control airways, only part of the bronchial epithelium and smooth muscle weakly
      expressed EGF receptor immunoreactivity. These results suggest a possible
      contribution of EGF to the pathophysiology of bronchial asthma, including airway
      remodeling.

PMID- 9620927
TI  - Transbronchial needle aspiration (TBNA) in patients infected with HIV.
AB  - Transbronchial needle aspiration (TBNA) of intrathoracic lymph nodes has been
      shown to be useful in the diagnosis and staging of bronchogenic carcinoma. With
      the exception of sarcoidosis, the usefulness of TBNA has not been widely
      investigated in other clinical settings. We investigated the utility of TBNA with
      a 19-gauge histology needle in HIV-infected patients with mediastinal and hilar
      adenopathy at Bellevue Hospital Center. We performed 44 procedures in 41
      patients. Adequate lymph node sampling was obtained in 35 of 44 (80%), and
      diagnostic material was obtained in 23 of 44 (52%) procedures. TBNA was the
      exclusive means of diagnosis in 13 of 41 (32%) patients. Of the 44 procedures, 23
      (52%) were performed in patients with mycobacterial disease, with TBNA providing
      the diagnosis in 20 of 23 (87%). In these patients, positive TBNA specimens
      included smears of aspirated materials for acid-fast bacilli in 11, mycobacterial
      culture in 14, and histology in 15. In other diseases, TBNA diagnosed sarcoidosis
      with noncaseating granulomata in 2 of 4 patients and non-small cell lung cancer
      in 1 of 2 patients. TBNA was not helpful in other diseases including Pneumocystis
      carinii pneumonia, infection with Cryptococcus or Nocardia, bacterial pneumonia,
      viral pneumonia, and Kaposi's sarcoma. No pulmonary diagnosis was established in
      five patients. No complications of TBNA occurred. We conclude that TBNA through
      the flexible bronchoscope is safe and effective in the diagnosis of intrathoracic
      adenopathy in HIV-infected patients, and is particularly efficacious in the
      diagnosis of mycobacterial disease. Furthermore, TBNA may provide the only
      diagnostic specimen in almost one-third of HIV-infected patients, thereby sparing
      these patients more invasive procedures such as mediastinoscopy.

PMID- 9620928
TI  - Synergistic hemodynamic effects of low-dose endotoxin and acute lung injury.
AB  - We evaluated the effects of low-dose endotoxin (15 microg/kg) on the pulmonary
      and systemic responses to oleic acid (OA)-induced acute lung injury in dogs.
      Animals given endotoxin alone (n = 5) showed a modest decrease in arterial blood
      pressure, but no effects on pulmonary hemodynamics, blood gases, cardiac output,
      or lung water accumulation. Animals (n = 6) given only OA (0.08 ml/kg) showed the
      expected development of mild-moderate pulmonary hypertension, a comparable
      reduction in arterial blood pressure, hypoxemia, increased lung water
      concentration, and an altered intrapulmonary perfusion pattern, as assessed by
      positron emission tomography. Animals (n = 7) given the same dose of endotoxin,
      followed 30 min later by the same dose of OA, developed a similar increase in
      lung water concentration as the group given OA alone, but failed to develop
      pulmonary hypertension or to redistribute pulmonary blood flow away from the
      edematous lung regions. In addition, arterial blood pressure fell significantly
      more than in the other groups. These responses were associated with a 30-fold
      increase in circulating prostacyclin (assayed as 6-keto prostaglandin F1 alpha
      [PGF1alpha]). The effects on systemic blood pressure, intrapulmonary blood flow
      redistribution, and eicosanoid production were eliminated by pretreating (n = 5)
      animals with meclofenamate (2 mg/kg). The results are consistent with a "priming"
      effect of low-dose endotoxin on the pulmonary endothelium, with exaggerated
      prostacyclin production in response to a subsequent lung injury. This interaction
      leads to altered intrapulmonary hemodynamics that exacerbate the development of
      hypoxemia, and to significant decreases in systemic blood pressure. To the extent
      that the lung is the most likely source of the increased prostacyclin production,
      the synergistic effects of low-dose endotoxin and lung injury may produce a kind
      of "lung shock."

PMID- 9620929
TI  - Platelet-activating factor induces goblet cell hyperplasia and mucin gene
      expression in airways.
AB  - In patients dying from asthma, extensive mucous plugging occurs in the airways,
      associated with goblet cell hyperplasia. In this study, we examined the
      hypothesis that platelet-activating factor (PAF) induces goblet cell hyperplasia
      and mucin gene expression. After instilling PAF into the airways of guinea pigs
      and rats, we stained airway goblet cells with Alcian blue/periodic acid-Schiff
      and determined the number of goblet cells and percentage of stained area within
      the epithelium. In guinea pigs, one instillation of PAF (10(-)5 M, 100 microl)
      increased the goblet cell-stained area time-dependently, beginning at 24 h,
      maximum at 72 h. PAF also caused tracheal recruitment of eosinophils by 24 h,
      maximum at 48 h. In rats, which have few goblet cells in airways, PAF (3
      instillations, 10(-)5 M, 200 microl) caused striking goblet cell hyperplasia,
      greatest in peripheral airways. Tumor necrosis factor alpha (TNFalpha) alone had
      no significant effect on goblet cells, but together with PAF, it caused
      exaggerated goblet cell hyperplasia. In rat tracheas studied by in situ
      hybridization, PAF induced mucin MUC5 gene expression in epithelial cells that
      stained for mucosubstances. In summary, PAF induces goblet cell hyperplasia and
      TNFalpha potentiates this effect.

PMID- 9620930
TI  - Consequences of vascular flow on lung injury induced by mechanical ventilation.
AB  - To investigate whether the magnitude of blood flow contributes to ventilator
      induced lung injury, 14 sets of isolated rabbit lungs were randomized for
      perfusion at either 300 (Group A: n = 7) or 900 ml/ min (Group B: n = 7) while
      ventilated with 30 cm H2O peak static pressure. Control lungs (Group C: n = 7)
      were ventilated with lower peak static pressure (15 cm H2O) and perfused at 500
      ml/min. Weight gain, changes in the ultrafiltration coefficient (DeltaKf) and
      lung static compliance (CL), and extent of hemorrhage (scored by histology) were
      compared. Group B had a larger decrease in CL (-13 +/- 11%) than Groups A (2 +/-
      6%) and C (5 +/- 5%) (p < 0.05). Group B had more hemorrhage and gained more
      weight (16.2 +/- 9.5 g) than Groups A (8.7 +/- 3.4 g) and C (1.6 +/- 1.0 g) (p <
      0.05 for each pairwise comparison between groups). Finally, Kf (g . min-1 . cm
      H2O-1 . 100 g-1) increased the most in Group B (DeltaKf = 0.26 +/- 0. 20 versus
      0.17 +/- 0.10 in Group A and 0.05 +/- 0.04 in Group C; p < 0.05 for B versus C).
      We conclude that the intensity of lung perfusion contributes to ventilator-
      induced lung injury in this model.

PMID- 9620931
TI  - Early inhibition of mycobacterial growth by human alveolar macrophages is not due
      to nitric oxide.
AB  - Phagocytic cells provide the first line of defense against mycobacteria. We
      examined the relative mycobacteriostatic contributions of normal human alveolar
      macrophages (HAM), peripheral blood monocytes (PBM), and polymorphonuclear
      leukocytes (PMN) in the early time period after infection with mycobacteria (48
      h). Cells were infected with Mycobacterium bovis (BCG) or M. tuberculosis H37Ra
      and their ability to inhibit growth was determined by mycobacterial incorporation
      of [3H]uracil. HAM inhibited the growth of both mycobacteria (44.2 +/- 7.9 and
      37.6 +/- 10.5% inhibition, respectively). Two populations of HAM donors were
      subsequently defined: inhibitors and noninhibitors. The ability to inhibit growth
      of H37Ra correlated with that of BCG. In contrast to HAM, PBM and PMN did not
      inhibit mycobacterial growth. Because nitric oxide (NO) has been proposed to
      mediate growth inhibition in murine models, we examined whether NO was
      responsible for the early growth inhibition of mycobacteria by HAM. As expected,
      in murine peritoneal macrophages (MPM) IFN-gamma (2,500 U/ml) enhanced growth
      inhibition of BCG; the effect was abolished by the nitric oxide synthase (NOS)
      inhibitor NMMA. In contrast, IFN-gamma failed to enhance growth inhibition by HAM
      or PBM and NMMA had no effect. MPM expressed inducible nitric oxide synthase
      (NOS2) mRNA in response to LPS and IFN-gamma and produced NO. Neither NOS2 mRNA
      nor NO could be detected in HAM stimulated with LPS and IFN-gamma or
      mycobacteria. These data demonstrate that HAM, but not PBM or PMN, have NO
      independent mycobacteriostatic activity in the early time period after infection
      with mycobacteria.

PMID- 9620932
TI  - Bronchial artery embolization for the treatment of hemoptysis in patients with
      cystic fibrosis.
AB  - Hemoptysis is common in patients with cystic fibrosis (CF). Bleeding may vary in
      severity, ranging from minor blood-streaking of sputum to expectoration of
      significant quantities of blood. Major hemoptysis, defined as bleeding greater
      than 240 ml/24 h, represents a medical emergency. Bronchial artery embolization
      (BAE) is one of the treatment options for hemoptysis. We reviewed the 10-yr
      experience at the University of North Carolina Hospitals in the treatment of
      hemoptysis by BAE. Eighteen patients with CF were hospitalized on 29 occasions
      and underwent 36 BAE procedures for the control of hemoptysis. Most patients (n =
      11) had very severe lung disease (FEV1 < 35%) with a high incidence (n = 9, 50%)
      of multi-drug-resistant bacteria. Fifteen patients (n = 33 procedures) were
      followed for a mean of approximately 22 mo after BAE. The overall efficacy of BAE
      for initial control of hemoptysis was 75% (n = 22) after one session, 89% (n =
      26) after two sessions, and 93% (n = 27) after three sessions. The overall
      recurrence rate per episode was 46% (12/26 presentations in four patients) with a
      mean time for recurrence of approximately 12 mo. There was a high incidence (75%)
      of bleeding from nonbronchial systemic collateral vessels among patients (n = 7)
      who had undergone a previous BAE. There were two deaths associated with massive
      hemoptysis despite BAE. Three patients had transient neurologic deficits during
      BAE. We concluded that BAE is a relatively safe and effective means of treating
      significant hemoptysis in patients with CF.

PMID- 9620933
TI  - Innervation of nasal turbinate blood vessels in rhinitic and nonrhinitic
      children.
AB  - An immunohistochemical study of the nasal mucosa was done in pediatric patients
      attending an otorhinolaringology (ORL) clinic. The goal was a comparison between
      vascular innervation in patients with or without symptoms of chronic rhinitis.
      All patients had an indication for tonsillectomy prior to their inclusion in this
      study. Samples were obtained under general anesthesia at the time of programmed
      surgery and fixed in a paraformaldehyde-picric acid mixture. Cryostat sections
      were immunostained for the following neuronal markers: protein-gene product 9.5
      (PGP), calcitonin gene- related peptide (CGRP), substance P (SP), and C-terminal
      peptide of neuropeptide Y (CPON). The following classes of vessels were
      identified: arteries, sinusoids, veins, and arteriovenous anastomoses (AVAs). As
      shown by immunostaining with the general neuronal marker PGP, each vessel type
      had a characteristic innervation pattern, differing in the amount of fibers and
      their distribution within the adventitial and muscle layers. Evaluation of PGP,
      CPON, and CGRP immunoreactivity patterns indicated that rhinitic arteries and
      AVAs displayed a richer innervation than did nonrhinitic blood vessels.
      Quantification of vascular PGP immunostaining confirmed the difference of
      vascular innervation between nonrhinitic and rhinitic patients. Fibers
      immunostained by CPON partially accounted for the rhinitic arterial
      hyperinnervation.

PMID- 9620934
TI  - Entry and intracellular growth of Legionella dumoffii in alveolar epithelial
      cells.
AB  - We have found that Legionella dumoffii strain Tex-KL (ATCC 33343) invades into
      and proliferates in the human lung alveolar epithelial-cell line A549 in vitro.
      The organism associated with the A549 cells at a 10-fold greater magnitude than
      L. pneumophila Philadelphia-1 during in vitro coculture for 1 h. Thereafter, L.
      dumoffii Tex-KL invaded the cells at a significantly higher rate (100- to 1,000
      fold) than did L. pneumophila Philadelphia-1. After internalization, however,
      both bacteria proliferated at the same rate. This in vitro finding led us to
      examine the bacterial localization in lungs in a fatal case of L. dumoffii
      pneumonia. Double immunostaining revealed the bacteria in surfactant apoprotein A
      positive cells (i.e., type II alveolar epithelial cells). Next, we infected
      guinea pigs intratracheally with L. dumoffii Tex-KL. The animals became sick with
      a fever from 24 h to 48 h after infection with 10(4) to 10(9) cfu of L. dumoffii
      Tex-KL. The lung tissues were examined through electron microscopy at definite
      intervals. Many bacteria were found not only inside phagocytic cells in the
      alveolar space, but also in type I and type II alveolar epithelial cells. These
      findings strongly suggest that L. dumoffii has an ability to invade into and
      proliferate in human alveolar epithelial cells, which may explain the rapid and
      fulminant progress of pneumonia caused by L. dumoffii.

PMID- 9620935
TI  - Efficacy of administering an endothelin-receptor antagonist (SB209670) in
      ameliorating ischemia-reperfusion injury in lung allografts.
AB  - The purpose of this study was to determine whether treatment with an endothelin-1
      (ET-1)-receptor antagonist could prevent ET-1-mediated ischemia-reperfusion
      injury and early allograft dysfunction. Eleven dogs were subjected to left lung
      allotransplantation. Donor lungs were preserved with modified Eurocollins
      solution and stored at 4 degrees C for 18 to 20 h. Animals received an
      intravenous infusion of either the ET-receptor antagonist SB209670 (n = 6) (15
      microg/kg/min) or saline (control, n = 5), in a blinded fashion. The infusion
      started 30 min before transplantation and continued for up to 6 h after
      transplantation. Hemodynamic measurements, blood gas tensions, and plasma samples
      were obtained with animals functioning solely on the transplanted lung. Open-lung
      biopsies were obtained for wet-to-dry-weight ratios and histologic and
      immunohistochemical analyses. Survival at 6 h after transplantation was 40% in
      the control group and 100% in the treatment group. Pulmonary vascular resistance
      and lung tissue wet-to-dry-weight ratio were significantly lower in treated
      animals at 3 and 6 h after transplantation. Histology of the transplanted lungs
      revealed more intense airway and interstitial inflammatory infiltration and edema
      in the control group. Arterial and venous plasma ET-1 concentrations increased
      after transplantation; however, they were significantly higher in the treatment
      group. Immunohistochemical analysis revealed more intense ET-1 immunostaining in
      the airways and parenchyma of the treatment group. We conclude that treatment of
      lung allografts with the mixed endothelin A/endothelin B (ETA/ETB) receptor
      antagonist SB209670 can ameliorate ischemia-reperfusion injury, resulting in
      improved graft function and survival after lung transplantation.

PMID- 9620936
TI  - PentaLyte decreases lung injury after aortic occlusion-reperfusion.
AB  - Lung injury often occurs after hepatoenteric ischemia, with xanthine oxidase (XO,
      an oxidant-generating enzyme), released from reperfusing liver and intestines,
      mediating a significant component of this injury. Since pentastarch
      administration decreases intestinal reperfusion injury, we determined whether
      resuscitation with PentaLyte (a pentastarch-containing solution) would decrease
      hepatoenteric reperfusion injury, xanthine oxidase release, and concomitant lung
      injury after aortic occlusion- reperfusion. Aortic occlusion was established in
      rabbits for 40 min, and was followed by 3 h of reperfusion, during which either
      PentaLyte or lactated Ringer's solution-based resuscitation was administered.
      Sham-operated animals served as controls. Hepatoenteric reperfusion injury, as
      manifested by release of the enzyme aspartate aminotransferase and decreased
      gastric intramucosal pH, was significantly (p < 0.0167) attenuated by PentaLyte
      administration after aortic occlusion-reperfusion, as compared with its
      occurrence in animals given lactated Ringer's solution. The release of XO after
      aortic occlusion-reperfusion was 4-fold smaller after PentaLyte administration
      than after resuscitation with lactated Ringer's solution (p < 0.05). Pulmonary
      injury, as defined by an increase in bronchoalveolar lavage fluid (BALF) protein
      content and lactate dehydrogenase (LDH) activity, was 4-fold less after PentaLyte
      administration following aortic occlusion-reperfusion than after administration
      of lactated Ringer's solution (p < 0.05). We conclude that remote pulmonary
      injury is significantly decreased by concomitant PentaLyte-mediated reduction of
      hepatoenteric reperfusion injury and XO release.

PMID- 9620937
TI  - Transfer of allergic airway responses with serum and lymphocytes from rats
      sensitized to dust mite.
AB  - House dust mite (HDM) antigen is one of the most common allergens associated with
      extrinsic asthma. In a model of allergic lung disease, Brown Norway (BN) rats
      sensitized to HDM with alum and Bordetella pertussis adjuvants produce high
      levels of IgE antibody and experience bronchoconstriction, increased airway
      hyperresponsiveness (AHR) to acetylcholine (ACh), and pulmonary inflammation
      after antigen challenge. The purpose of this study was to determine whether these
      asthmatic symptoms could be transferred from sensitized animals to naive
      recipients via humoral or cellular factors. Syngeneic recipient rats were
      injected (intraperitoneally with 4 x 10(7) cells (precultured overnight with
      either HDM or bovine serum albumin [BSA]) from lymph nodes of sensitized or
      control rats, respectively. Other groups received a tail-vein injection of serum
      from either HDM-sensitized or control rats. Antigen challenge in rats injected
      with sensitized cells caused increases in pulmonary inflammation and in AHR, but
      no changes in immediate bronchoconstriction as compared with control recipients.
      Antigen challenge in serum recipients resulted in immediate bronchoconstriction
      but had no effect on AHR or on pulmonary inflammation. These data show that
      immune-mediated lung inflammation and AHR are promoted by antigen-specific
      lymphocytes, whereas immediate allergic responses are caused by serum factors.

PMID- 9620938
TI  - Number and proliferation of basal and parabasal cells in normal human airway
      epithelium.
AB  - Two roles have been suggested for basal cells on the basis of studies performed
      with laboratory animals: (1) anchoring of the tracheobronchial epithelium; and
      (2) being the epithelial stem cell. Parabasal cells located just above the basal
      cells have also been shown to contribute to cell renewal. However, a systematic
      study of the composition and proliferation of basal and parabasal cells in normal
      human lungs is lacking. The aims of this study were to determine in normal human
      conducting-airway epithelium: (1) the number of basal and parabasal cells; and
      (2) the contribution of basal and parabasal cells to the proliferation fraction.
      Samples of histologically normal tissue, free of pulmonary disease, were taken
      from seven lungs obtained by autopsy. Immunohistochemical staining was performed
      with the primary antibody MIB-1 as a proliferation marker and the antikeratin
      antibody 34betaE12 as a marker for basal and parabasal cells. In the largest
      conducting airways (diameter >= 4 mm), the percentages of basal and parabasal
      cells were 31% and 7%, respectively; the contribution to the proliferation
      compartment was 51% for basal and 33% for parabasal cells. In the smallest
      airways (diameter < 0.5 mm), 6% of epithelial cells were basal cells, with a 30%
      contribution to the proliferation compartment, whereas parabasal cells were
      absent. The high fraction of basal and parabasal cells contributing to the
      proliferation compartment of normal human conducting-airway epithelium supports
      the theory that cells at or near the basement membrane are likely to be
      progenitor cells.

PMID- 9620940
TI  - Foreword 

PMID- 9620939
TI  - Relapsing nodular lesions in the course of adult pulmonary Langerhans cell
      histiocytosis.
AB  - In most patients with pulmonary Langerhans cell histiocytosis (LCH), clinical and
      radiological abnormalities initially either stabilize or regress, often without
      treatment. Little information is available, however, concerning the subsequent
      evolution of disease in patients who initially follow a benign course. We
      describe four patients with biopsy-confirmed pulmonary LCH whose initial course
      was characterized by regression of parenchymal nodular lesions, but who
      subsequently developed one or more episodes of active disease 7 mo to 7.5 yr
      after their initial presentation. In each case, the subsequent episodes of active
      disease were characterized by the reappearance or marked increase in nodular
      radiographic abnormalities, whose presence was confirmed by high-resolution
      computed tomography (HRCT). Thus, initial regression of nodular lesions in
      pulmonary LCH does not preclude the reappearance of one or more episodes of
      active disease, and may have important consequences on the long-term prognosis of
      these patients.

PMID- 9620941
TI  - Leukotrienes and inflammation 
AB  - Leukotrienes are potent pro-inflammatory mediators that appear to contribute to
      pathophysiologic features of asthma. For example, cysteinyl leukotrienes contract
      airway smooth muscle, increase microvascular permeability, stimulate mucus
      secretion, decrease mucociliary clearance, and appear capable of recruiting
      eosinophils into the airways. Segmental antigen bronchoprovocation in patients
      with asthma increases LTC4 concentrations in bronchoalveolar lavage fluid, which
      correlates with an influx of eosinophils into the airways. LTB4, in comparison,
      selectively affects neutrophil functions. Intratracheal instillation of LTB4
      produced a selective recruitment of neutrophils into the lung. These effects
      suggest that leukotrienes contribute significantly to the inflammatory components
      of asthma. Busse WW. Leukotrienes and inflammation.

PMID- 9620942
TI  - Pharmacology of leukotriene receptor antagonists 
AB  - Preclinical pharmacological studies have demonstrated that cysLT1 receptor
      antagonists, such as zafirlukast, montelukast, and pobilukast, are potent and
      selective antagonists of cysteinyl leukotriene (cysLT) activity. In vitro, these
      agents compete with [3H]LTD4 for binding to cysLT1 receptors present on guinea
      pig and human lung cell membranes. Both zafirlukast and montelukast have
      affinities that are approximately two times greater than that of the natural
      ligand, LTD4. These agents block LTD4- and LTE4-induced contractions of isolated
      guinea pig trachea, but do not antagonize LTC4-induced contractions, which are
      putatively mediated by a different LT receptor, cysLT2. The cysLT2 receptor,
      however, has not yet been found in human airway smooth muscle. In animal models,
      these drugs inhibit LTD4-, LTE4-, and antigen-induced bronchoconstriction, reduce
      inflammatory markers in models of pulmonary inflammation, and inhibit antigen
      induced late-phase bronchoconstriction. This preclinical profile suggests that
      cysLT1 receptor antagonists may be useful in treating inflammatory conditions of
      the respiratory system, such as asthma and allergic rhinitis. Aharony D.
      Pharmacology of leukotriene receptor antagonists.

PMID- 9620943
TI  - Chemistry and structure-activity relationships of leukotriene receptor
      antagonists 
AB  - Several strategies have been employed by medicinal chemists in the design of
      potent and selective leukotriene receptor antagonists-leukotriene structural
      analogs, FPL 55712 analogs, and random screening of corporate compound banks.
      Lead compounds were optimized, often through the exchange of ideas with groups
      working on other chemical series of leukotriene antagonists. Pranlukast can
      likely be traced to a lead compound identified by random screening that was
      initially modified by incorporating structural components present in FPL 55712.
      Montelukast originated from an early quinoline lead, which was modified with
      leukotriene structural elements. Zafirlukast is based on a lead compound that
      incorporated structural components from both FPL 55712 and the leukotrienes.
      Therefore, each medicinal chemistry strategy that was originally employed has
      successfully identified clinically effective leukotriene receptor antagonists.
      Bernstein PR. Chemistry and structure-activity relationships of leukotriene
      receptor antagonists.

PMID- 9620944
TI  - Cell biology of the 5-lipoxygenase pathway 
AB  - The initial enzymatic steps in leukotriene synthesis occur at the nuclear
      envelope. Cytosolic phospholipase A2 translocates from the cytoplasm to
      selectively hydrolyze nuclear envelope phospholipids, releasing free
      arachidonate. 5-Lipoxygenase-activating protein, an arachidonate transfer
      protein, then binds arachidonate and presents it to 5-lipoxygenase (5-LO), which
      catalyzes a two-step reaction to produce leukotriene A4. In resting human and rat
      peripheral blood neutrophils, 5-LO is localized to the cytoplasm; in rat
      basophilic leukemia cells and human alveolar macrophages, however, it is found
      predominantly in the nucleus. Immunofluorescence microscopy studies demonstrate
      that both cytoplasmic and nuclear 5-LO move to the nuclear envelope following
      cell activation. Many questions remain unanswered regarding the significance of
      nuclear 5-LO, potential autocrine actions of leukotrienes, and intracellular
      trafficking of these enzymes and their products. Peters-Golden M. Cell biology of
      the 5-lipoxygenase pathway.

PMID- 9620945
TI  - Clinical pharmacology of leukotriene receptor antagonists and 5-lipoxygenase
      inhibitors 
AB  - Blinded, randomized, and placebo-controlled clinical trials have established that
      cysteinyl leukotriene (cysLT) receptor antagonists and 5-lipoxygenase (5-LO)
      inhibitors are safe and effective asthma treatments. Trials of 13- to 26-wks'
      duration demonstrate that both the cysLT1 receptor antagonist, zafirlukast, and
      the 5-LO inhibitor, zileuton, improve pulmonary function and decrease daytime and
      nocturnal symptoms. Concomitant rescue beta-agonist inhaler use and the need for
      corticosteroid rescue are also reduced. Preliminary studies suggest that
      antileukotriene agents may also reduce indices of airway inflammation, including
      inflammatory cell counts and airway hyperresponsiveness. Both cysLT1 antagonists
      and 5-LO inhibitors offer a new approach to asthma management. Drazen J. Clinical
      pharmacology of leukotriene receptor antagonists and 5-lipoxygenase inhibitors.

PMID- 9620946
TI  - Summary of clinical trials with zafirlukast 
AB  - Zafirlukast is an orally active and selective cysteinyl leukotriene (cysLT)
      receptor antagonist. In humans, zafirlukast antagonized the effects of
      exogenously administered LTD4 and cysLTs released endogenously in response to
      physical and chemical stimuli. Zafirlukast antagonized LTD4-induced
      bronchoconstriction, with effects still evident 12 h after drug administration.
      In clinical models of asthma, zafirlukast inhibited bronchospasm after allergen
      or exercise challenge in patients with asthma. In multicenter trials in patients
      with chronic, stable asthma, zafirlukast reduced asthma symptoms, decreased as
      needed beta-agonist use, and improved pulmonary function without increasing the
      number of adverse events. Zafirlukast also exhibited evidence of an anti
      inflammatory effect in the lung in preliminary studies involving segmental
      antigen challenge. The results from these clinical trials demonstrate that
      zafirlukast is effective and safe for the prophylactic treatment of asthma.
      Calhoun WJ. Summary of clinical trials with zafirlukast.

PMID- 9620947
TI  - General discussion 

PMID- 9620949
TI  - In vivo analysis of sequence requirements for processing and degradation of the
      colicin A lysis protein signal peptide.
AB  - The lipid modification and processing of a number of colicin lysis proteins take
      place exceedingly slowly and result in the release of a stable signal peptide. It
      is possible that this peptide or the presence of lipid-modified precursors which
      result from the slow processing plays a role in the release of colicins and in
      the quasilysis that occurs in induced colicinogenic cultures. We used in vitro
      mutagenesis and pulse-chase radiolabeling and immunoprecipitation to examine the
      reasons for the slow processing and signal peptide degradation reactions for the
      colicin A lysis protein (Cal). In one mutant, isoleucine 13 was replaced with
      serine, and in another, alanine 18, the last residue of the signal peptide, was
      replaced with glycine. In each case, the mutation caused a striking increase in
      the rate of maturation of the precursor, and in the case of the serine 13
      derivative, the mutation also destabilized the signal peptide. A precursor
      containing both of these mutations was completely matured and its signal sequence
      degraded within seconds of its synthesis. The release of colicin A and the
      quasilysis of producing cultures were unchanged for each of these mutants,
      indicating that neither the stable signal peptide nor lipid-modified processing
      intermediates of Cal are required for either of these events in wild-type cells.

PMID- 9620948
TI  - RNA polymerase-promoter interactions: the comings and goings of RNA polymerase.

PMID- 9620950
TI  - The developmentally regulated alb1 gene of Aspergillus fumigatus: its role in
      modulation of conidial morphology and virulence.
AB  - Aspergillus fumigatus, an important opportunistic pathogen which commonly affects
      neutropenic patients, produces conidia with a bluish-green color. We identified a
      gene, alb1, which is required for conidial pigmentation. The alb1 gene encodes a
      putative polyketide synthase, and disruption of alb1 resulted in an albino
      conidial phenotype. Expression of alb1 is developmentally regulated, and the 7-kb
      transcript is detected only during the conidiation stage. The alb1 mutation was
      found to block 1,3,6,8-tetrahydroxynaphthalene production, indicating that alb1
      is involved in dihydroxynaphthalene-melanin biosynthesis. Scanning electron
      microscopy studies showed that the alb1 disruptant exhibited a smooth conidial
      surface, whereas complementation of the alb1 deletion restored the echinulate
      wild-type surface. Disruption of alb1 resulted in a significant increase in C3
      binding on conidial surfaces, and the conidia of the alb1 disruptant were
      ingested by human neutrophils at a higher rate than were those of the wild type.
      The alb1-complemented strain producing bluish-green conidia exhibited inefficient
      C3 binding and neutrophil-mediated phagocytosis quantitatively similar to those
      of the wild type. Importantly, the alb1 disruptant had a statistically
      significant loss of virulence compared to the wild-type and alb1-complemented
      strains in a murine model. These results suggest that disruption of alb1 causes
      pleiotropic effects on conidial morphology and fungal virulence.

PMID- 9620951
TI  - Target choice and orientation preference of the insertion sequence IS903.
AB  - We have examined the targeting preference of the bacterial insertion element
      IS903 by determining the sites of insertion of a large number of transposition
      events into the 55-kb conjugative plasmid pOX38. Despite the large target size,
      all the insertions were clustered in four small distinct regions associated with
      conjugal DNA transfer. Within these regions, many different sites were used for
      insertion; however, there were a few sites that IS903 inserted into more than
      once. Alignment of the insertion sites showed that there was no consensus
      sequence within the 9-bp target duplication but that there were preferred
      sequences located symmetrically on either side of the target. This is consistent
      with target recognition by a dimer or multimer of transposase, with either
      sequence-specific or structure-specific interactions on both sides of the target.
      We show further that when one of these preferred regions was cloned into a second
      conjugative plasmid, pUB307, it was still a preferred target, implying that all
      the sequences necessary for target selection are contained within this DNA
      segment. Also, we observed a very strong preference for insertion in a single
      orientation in pUB307. We examined the possibility that either DNA replication
      from the origin of vegetative replication, oriV, or the origin of transfer, oriT,
      might determine this orientation effect. We find that reversing the direction of
      vegetative replication had no effect on the orientation of transposon insertions;
      however, reversing the direction of DNA transfer abolished the orientation
      effect. This supports the idea that conjugal DNA transfer imparts a polarity on
      the target that is sensed by the transposon.

PMID- 9620952
TI  - Cloning of the Lactococcus lactis adhE gene, encoding a multifunctional alcohol
      dehydrogenase, by complementation of a fermentative mutant of Escherichia coli.
AB  - The Lactococcus lactis adhE gene, which encodes a multifunctional alcohol
      dehydrogenase, has been cloned and characterized. A DNA fragment encoding the
      putative alcohol dehydrogenase domain of the AdhE protein was cloned by screening
      an L. lactis genomic library in a fermentative mutant of Escherichia coli and
      selecting for the ability to grow anaerobically. Further analysis of the clone
      obtained allowed the cloning of the entire adhE gene sequence. Analysis of adhE
      expression in L. lactis during anaerobiosis showed induction at the
      transcriptional level, especially in medium containing glucose. Constructed
      mutant strains produced reduced amounts of ethanol under anaerobic conditions.
      With the L. lactis gene as a probe, adhE homologs were found in other
      industrially relevant lactic acid bacteria.

PMID- 9620953
TI  - Replicase, excisionase, and integrase genes of the Streptomyces element pSAM2
      constitute an operon positively regulated by the pra gene.
AB  - pSAM2 is a site-specific integrative element from Streptomyces ambofaciens. The
      pra gene described earlier as an activator of pSAM2 replication is shown here to
      be also involved in the activation of its integration and excision. This was
      evidenced with derivatives of pSAM2 mutant B3 in which the pra gene was placed
      under the control of the inducible tipAp promoter. Transformation of Streptomyces
      lividans by these derivatives was efficient only when pra expression was induced,
      indicating its involvement in pSAM2 integration activation. Once established,
      these constructions remained integrated in the chromosome under noninduced
      conditions. Activation of the pra expression provoked strong activation of their
      excision, leading to the appearance of free forms. The results of functional,
      transcriptional, and sequence analyses allowed to conclude that the three genes
      repSA, xis, and int coding for the pSAM2 replicase, excisionase, and integrase,
      respectively, constitute an operon directly or indirectly activated by pra.

PMID- 9620954
TI  - The Caulobacter crescentus paracrystalline S-layer protein is secreted by an ABC
      transporter (type I) secretion apparatus.
AB  - Caulobacter crescentus is a gram-negative bacterium that produces a two
      dimensional crystalline array on its surface composed of a single 98-kDa protein,
      RsaA. Secretion of RsaA to the cell surface relies on an uncleaved C-terminal
      secretion signal. In this report, we identify two genes encoding components of
      the RsaA secretion apparatus. These components are part of a type I secretion
      system involving an ABC transporter protein. These genes, lying immediately 3' of
      rsaA, were found by screening a Tn5 transposon library for the loss of RsaA
      transport and characterizing the transposon-interrupted genes. The two proteins
      presumably encoded by these genes were found to have significant sequence
      similarity to ABC transporter and membrane fusion proteins of other type I
      secretion systems. The greatest sequence similarity was found to the alkaline
      protease (AprA) transport system of Pseudomonas aeruginosa and the
      metalloprotease (PrtB) transport system of Erwinia chrysanthemi. The prtB and
      aprA genes were introduced into C. crescentus, and their products were secreted
      by the RsaA transport system. Further, defects in the S-layer protein transport
      system led to the loss of this heterologous secretion. This is the first report
      of an S-layer protein secreted by a type I secretion apparatus. Unlike other type
      I secretion systems, the RsaA transport system secretes large amounts of its
      substrate protein (it is estimated that RsaA accounts for 10 to 12% of the total
      cell protein). Such levels are expected for bacterial S-layer proteins but are
      higher than for any other known type I secretion system.

PMID- 9620955
TI  - Promoter region of the Escherichia coli O7-specific lipopolysaccharide gene
      cluster: structural and functional characterization of an upstream untranslated
      mRNA sequence.
AB  - We report the identification of the promoter region of the Escherichia coli O7
      specific lipopolysaccharide (LPS) gene cluster (wbEcO7). Typical -10 and -35
      sequences were found to be located in the intervening region between galF and
      rlmB, the first gene of the wbEcO7 cluster. Data from RNase protection
      experiments revealed the existence of an untranslated leader mRNA segment of 173
      bp, including the JUMPStart and two ops sequences. We characterized the structure
      of this leader mRNA by using the program Mfold and a combination of nested and
      internal deletions transcriptionally fused to a promoterless lac operon. Our
      results indicated that the leader mRNA may fold into a series of complex stem
      loop structures, one of which includes the JUMPStart element. We have also found
      that one of the ops sequences resides on the predicted stem and the other resides
      on the loop region, and we confirmed that these sequences are essential for the
      RfaH-mediated regulation of the O polysaccharide cluster. A very similar stem
      loop structure could be predicted in the promoter region of the LPS core operon
      encoding the waaQGPSBIJYZK genes. We observed another predicted stem-loop,
      located immediately downstream from the wbEcO7 transcription initiation site,
      which appeared to be involved in premature termination of transcription. This
      putative stem-loop is common to many other O polysaccharide gene clusters but is
      not present in core oligosaccharide genes. wbEcO7-lac transcriptional fusions in
      single copy numbers were also used to determine the effects of various
      environmental cues in the transcriptional regulation of O polysaccharide
      synthesis. No effects were detected with temperature, osmolarity, Mg2+
      concentration, and drugs inducing changes in DNA supercoiling. We therefore
      conclude that the wbEcO7 promoter activity may be constitutive and that
      regulation takes place at the level of elongation of the mRNA in a RfaH-mediated
      manner.

PMID- 9620956
TI  - Preparation and characterization of Neisseria meningitidis mutants deficient in
      production of the human lactoferrin-binding proteins LbpA and LbpB.
AB  - Pathogenic members of the family Neisseriaceae produce specific receptors
      facilitating iron acquisition from transferrin (Tf) and lactoferrin (Lf) of their
      mammalian host. Tf receptors are composed of two outer membrane proteins, Tf
      binding proteins A and B (TbpA and TbpB; formerly designated Tbp1 and Tbp2,
      respectively). Although only a single Lf-binding protein, LbpA (formerly
      designated Lbp1), had previously been recognized, we recently identified
      additional bacterial Lf-binding proteins in the human pathogens Neisseria
      meningitidis and Moraxella catarrhalis and the bovine pathogen Moraxella bovis by
      a modified affinity isolation technique (R. A. Bonnah, R.-H. Yu, and A. B.
      Schryvers, Microb. Pathog. 19:285-297, 1995). In this report, we characterize an
      open reading frame (ORF) located immediately upstream of the N. meningitidis
      B16B6 lbpA gene. Amino acid sequence comparisons of various TbpBs with the
      product of the translated DNA sequence from the upstream ORF suggests that the
      region encodes the Lf-binding protein B homolog (LbpB). The LbpB from strain
      B16B6 has two large stretches of negatively charged amino acids that are not
      present in the various transferrin receptor homologs (TbpBs). Expression of the
      recombinant LbpB protein as a fusion with maltose binding protein demonstrated
      functional Lf-binding activity. Studies with N. meningitidis isogenic mutants in
      which the lbpA gene and the ORF immediately upstream of lbpA (putative lbpB gene)
      were insertionally inactivated demonstrated that LbpA, but not LbpB, is essential
      for iron acquisition from Lf in vitro.

PMID- 9620957
TI  - Multidomain structure and cellulosomal localization of the Clostridium
      thermocellum cellobiohydrolase CbhA.
AB  - The nucleotide sequence of the Clostridium thermocellum F7 cbhA gene, coding for
      the cellobiohydrolase CbhA, has been determined. An open reading frame encoding a
      protein of 1,230 amino acids was identified. Removal of a putative signal peptide
      yields a mature protein of 1,203 amino acids with a molecular weight of 135,139.
      Sequence analysis of CbhA reveals a multidomain structure of unusual complexity
      consisting of an N-terminal cellulose binding domain (CBD) homologous to CBD
      family IV, an immunoglobulin-like beta-barrel domain, a catalytic domain
      homologous to cellulase family E1, a duplicated domain similar to fibronectin
      type III (Fn3) modules, a CBD homologous to family III, a highly acidic linker
      region, and a C-terminal dockerin domain. The cellulosomal localization of CbhA
      was confirmed by Western blot analysis employing polyclonal antibodies raised
      against a truncated enzymatically active version of CbhA. CbhA was identified as
      cellulosomal subunit S3 by partial amino acid sequence analysis. Comparison of
      the multidomain structures indicates striking similarities between CbhA and a
      group of cellulases from actinomycetes. Average linkage cluster analysis suggests
      a coevolution of the N-terminal CBD and the catalytic domain and its spread by
      horizontal gene transfer among gram-positive cellulolytic bacteria.

PMID- 9620958
TI  - Transcriptional regulation of Streptomyces coelicolor pathway-specific antibiotic
      regulators by the absA and absB loci.
AB  - The four antibiotics produced by Streptomyces coelicolor are all affected by
      mutations in the absA and absB loci. The absA locus encodes a putative two
      component signal transduction system, and the absB locus encodes a homolog of
      Escherichia coli RNase III. We assessed whether these loci control synthesis of
      the antibiotics actinorhodin and undecylprodigiosin by regulating transcript
      abundance from the biosynthetic and regulatory genes specific for each
      antibiotic. Strains that were Abs- (for antibiotic synthesis deficient) due to
      mutations in absA or absB were examined. In the Abs- absA mutant strain,
      transcripts for the actinorhodin biosynthetic genes actVI-ORF1 and actI, and for
      the pathway-specific regulatory gene actII-ORF4, were substantially lower in
      abundance than in the parent strain. The level of the transcript for the
      undecylprodigiosin pathway-specific regulatory gene redD was similarly reduced in
      this mutant. Additionally, a strain that exhibits precocious hyperproduction of
      antibiotics (Pha phenotype) due to disruption of the absA locus contained
      elevated levels of the actVI-ORF1, actII-ORF4, and redD transcripts. In the absB
      mutant strain, actVI-ORF1, actI, actII-ORF4, and redD transcript levels were also
      substantially lower than in the parent strain. These results establish that the
      abs genes affect production of antibiotics through regulation of expression of
      the antibiotic-specific regulatory genes in S. coelicolor.

PMID- 9620959
TI  - An isoflavonoid-inducible efflux pump in Agrobacterium tumefaciens is involved in
      competitive colonization of roots.
AB  - Agrobacterium tumefaciens 1D1609, which was originally isolated from alfalfa
      (Medicago sativa L.), contains genes that increase competitive root colonization
      on that plant by reducing the accumulation of alfalfa isoflavonoids in the
      bacterial cells. Mutant strain I-1 was isolated by its isoflavonoid-inducible
      neomycin resistance following mutagenesis with the transposable promoter probe
      Tn5-B30. Nucleotide sequence analysis showed the transposon had inserted in the
      first open reading frame, ifeA, of a three-gene locus (ifeA, ifeB, and ifeR),
      which shows high homology to bacterial efflux pump operons. Assays on alfalfa
      showed that mutant strain I-1 colonized roots normally in single-strain tests but
      was impaired significantly (P < or = 0.01) in competition against wild-type
      strain 1D1609. Site-directed mutagenesis experiments, which produced strains I-4
      (ifeA::gusA) and I-6 (ifeA::omega-Tc), confirmed the importance of ifeA for
      competitive root colonization. Exposure to the isoflavonoid coumestrol increased
      beta-glucuronidase activity in strain I-4 21-fold during the period when
      coumestrol accumulation in wild-type cells declined. In the same test, coumestrol
      accumulation in mutant strain I-6 did not decline. Expression of the ifeA-gusA
      reporter was also induced by the alfalfa root isoflavonoids formononetin and
      medicarpin but not by two triterpenoids present in alfalfa. These results show
      that an efflux pump can confer measurable ecological benefits on A. tumefaciens
      in an environment where the inducing molecules are known to be present.

PMID- 9620960
TI  - Changes in ribosomal activity of Escherichia coli cells during prolonged culture
      in sea salts medium.
AB  - The activity of ribosomes from a clinical isolate of Escherichia coli, exposed to
      starvation for 7 days in sea salts medium, was investigated by measuring the
      kinetic parameters of ribosomal peptidyltransferase, by using the puromycin
      reaction as a model reaction. No alterations in the extent of peptide bond
      formation were observed during starvation. In contrast, a 50% reduction in the
      kmax/Ks ratio could be seen after 24 h of starvation; an additional 6 days of
      starvation resulted in a progressive but less abrupt decline in the kmax/Ks
      value. (kmax is the apparent catalytic rate constant of peptidyl transferase, and
      Ks is the dissociation constant of the encounter complex between acetyl
      (Ac)[3H]Phe-tRNA-poly(U)-ribosome and puromycin.) Although the distribution of
      ribosomal particles remained constant, a substantial decrease in the number of
      ribosomes per starved cell and a clear decline in the ability of ribosomes to
      bind AcPhe-tRNA were observed, particularly during the first day of starvation.
      Further analysis indicated that rRNA in general, but especially 23S rRNA, was
      rapidly degraded during the starvation period. In addition, the L12/L7 molar
      ratio decreased from 1.5 to 1 during the initial phase of starvation (up to 24 h)
      but remained constant during the subsequent starvation period. Ribosomes isolated
      from 24-h-starved cells, when artificially depleted of L7/L12 protein and
      reconstituted with L7/L12 protein from mid-logarithmic-phase cells, regenerated
      an L12/L7 molar ratio of 1.5 and restored the peptidyltransferase activity to a
      substantial level. An analogous effect of reconstitution on the efficiency of
      ribosomes in binding AcPhe-tRNA was evident not only during the initial phase but
      throughout the starvation period.

PMID- 9620961
TI  - Folding-based suppression of extracytoplasmic toxicity conferred by processing
      defective LamB.
AB  - We have utilized processing-defective derivatives of the outer membrane
      maltoporin, LamB, to study protein trafficking functions in the cell envelope of
      Escherichia coli. Our model proteins contain amino acid substitutions in the
      consensus site for cleavage by signal peptidase. As a result, the signal sequence
      is cleaved with reduced efficiency, effectively tethering the precursor protein
      to the inner membrane. These mutant porins are toxic when secreted to the cell
      envelope. Furthermore, strains producing these proteins exhibit altered outer
      membrane permeability, suggesting that the toxicity stems from some perturbation
      of the cell envelope (J. H. Carlson and T. J. Silhavy, J. Bacteriol. 175:3327
      3334, 1993). We have characterized a multicopy suppressor of the processing
      defective porins that appears to act by a novel mechanism. Using fractionation
      experiments and conformation-specific antibodies, we found that the presence of
      this multicopy suppressor allowed the processing-defective LamB precursors to be
      folded and localized to the outer membrane. Analysis of the suppressor plasmid
      revealed that these effects are mediated by the presence of a truncated
      derivative of the polytopic inner membrane protein, TetA. The suppression
      mediated by TetA' is independent of the CpxA/CpxR regulon and the sigma E
      regulon, both of which are involved in regulating protein trafficking functions
      in the cell envelope.

PMID- 9620962
TI  - Altered Na+ and Li+ homeostasis in Saccharomyces cerevisiae cells expressing the
      bacterial cation antiporter NhaA.
AB  - The bacterial Na+ (Li+)/H+ antiporter NhaA has been expressed in the yeast
      Saccharomyces cerevisiae. NhaA was present in both the plasma membrane and
      internal membranes, and it conferred lithium but not sodium tolerance. In cells
      containing the yeast Ena1-4 (Na+, Li+) extrusion ATPase, the extra lithium
      tolerance conferred by NhaA was dependent on a functional vacuolar H+ ATPase and
      correlated with an increase of lithium in an intracellular pool which exhibited
      slow efflux of cations. In yeast mutants without (Na+, Li+) ATPase, lithium
      tolerance conferred by NhaA was not dependent on a functional vacuolar H+ ATPase
      and correlated with a decrease of intracellular lithium. NhaA was able to confer
      sodium tolerance and to decrease intracellular sodium accumulation in a double
      mutant devoid of both plasma membrane (Na+, Li+) ATPase and vacuolar H+ ATPase.
      These results indicate that the bacterial antiporter NhaA expressed in yeast is
      functional at both the plasma membrane and the vacuolar membrane. The phenotypes
      conferred by its expression depend on the functionally of plasma membrane (Na+,
      Li+) ATPase and vacuolar H+ ATPase.

PMID- 9620963
TI  - Anaerobic growth, a property horizontally transferred by an Hfr-like mechanism
      among extreme thermophiles.
AB  - Despite the fact that the extreme thermophilic bacteria belonging to the genus
      Thermus are classified as strict aerobes, we have shown that Thermus thermophilus
      HB8 (ATCC 27634) can grow anaerobically when nitrate is present in the growth
      medium. This strain-specific property is encoded by a respiratory nitrate
      reductase gene cluster (nar) whose expression is induced by anoxia and nitrate
      (S. Ramirez-Arcos, L. A. Fernandez-Herrero, and J. Berenguer, Biochim. Biophys.
      Acta, 1396:215-1997). We show here that this nar operon can be transferred by
      conjugation to an aerobic Thermus strain, enabling it to grow under anaerobic
      conditions. We show that this transfer takes place through a DNase-insensitive
      mechanism which, as for the Hfr (high frequency of recombination) derivatives of
      Escherichia coli, can also mobilize other chromosomal markers in a time-dependent
      way. Three lines of evidence are presented to support a genetic linkage between
      nar and a conjugative plasmid integrated into the chromosome. First, the nar
      operon is absent from a plasmid-free derivative and from a closely related
      strain. Second, we have identified an origin for autonomous replication (oriV)
      overlapping the last gene of the nar cluster. Finally, the mating time required
      for the transfer of the nar operon is in good agreement with the time expected if
      the transfer origin (oriT) were located nearby and downstream of nar.

PMID- 9620964
TI  - The ms2io6A37 modification of tRNA in Salmonella typhimurium regulates growth on
      citric acid cycle intermediates.
AB  - The modified nucleoside 2-methylthio-N-6-isopentenyl adenosine (ms2i6A) is
      present in position 37 (adjacent to and 3' of the anticodon) of tRNAs that read
      codons beginning with U except tRNA(i.v. Ser) in Escherichia coli. In Salmonella
      typhimurium, 2-methylthio-N-6-(cis-hydroxy)isopentenyl adenosine (ms2io6A; also
      referred to as 2-methylthio cis-ribozeatin) is found in tRNA, most likely in the
      species that have ms2i6A in E. coli. Mutants (miaE) of S. typhimurium in which
      ms2i6A hydroxylation is blocked are unable to grow aerobically on the
      dicarboxylic acids of the citric acid cycle. Such mutants have normal uptake of
      dicarboxylic acids and functional enzymes of the citric acid cycle and the
      aerobic respiratory chain. The ability of S. typhimurium to grow on succinate,
      fumarate, and malate is dependent on the state of modification in position 37 of
      those tRNAs normally having ms2io6A37 and is not due to a second cellular
      function of tRNA (ms2io6A37)hydroxylase, the miaE gene product. We suggest that
      S. typhimurium senses the hydroxylation status of the isopentenyl group of the
      tRNA and will grow on succinate, fumarate, or malate only if the isopentenyl
      group is hydroxylated.

PMID- 9620965
TI  - Acyl coenzyme A synthetase from Pseudomonas fragi catalyzes the synthesis of
      adenosine 5'-polyphosphates and dinucleoside polyphosphates.
AB  - Acyl coenzyme A (CoA) synthetase (EC 6.2.1.8) from Pseudomonas fragi catalyzes
      the synthesis of adenosine 5'-tetraphosphate (p4A) and adenosine 5'
      pentaphosphate (p5A) from ATP and tri- or tetrapolyphosphate, respectively. dATP,
      adenosine-5'-O-[gamma-thiotriphosphate] (ATP gamma S),
      adenosine(5')tetraphospho(5')adenosine (Ap4A), and
      adenosine(5')pentaphospho(5')adenosine (Ap5A) are also substrates of the reaction
      yielding p4(d)A in the presence of tripolyphosphate (P3). UTP, CTP, and AMP are
      not substrates of the reaction. The K(m) values for ATP and P3 are 0.015 and 1.3
      mM, respectively. Maximum velocity was obtained in the presence of MgCl2 or CoCl2
      equimolecular with the sum of ATP and P3. The relative rates of synthesis of p4A
      with divalent cations were Mg = Co > Mn = Zn >> Ca. In the pH range used, maximum
      and minimum activities were measured at pH values of 5.5 and 8.2, respectively;
      the opposite was observed for the synthesis of palmitoyl-CoA, with maximum
      activity in the alkaline range. The relative rates of synthesis of palmitoyl-CoA
      and p4A are around 10 (at pH 5.5) and around 200 (at pH 8.2). The synthesis of
      p4A is inhibited by CoA, and the inhibitory effect of CoA can be counteracted by
      fatty acids. To a lesser extent, the enzyme catalyzes the synthesis also of Ap4A
      (from ATP), Ap5A (from p4A), and adenosine(5')tetraphospho(5')nucleoside (Ap4N)
      from adequate adenylyl donors (ATP, ATP gamma S, or octanoyl-AMP) and adequate
      adenylyl acceptors (nucleoside triphosphates).

PMID- 9620966
TI  - Different modes of diaminopimelate synthesis and their role in cell wall
      integrity: a study with Corynebacterium glutamicum.
AB  - In eubacteria, there are three slightly different pathways for the synthesis of m
      diaminopimelate (m-DAP), which is one of the key linking units of peptidoglycan.
      Surprisingly, for unknown reasons, some bacteria use two of these pathways
      together. An example is Corynebacterium glutamicum, which uses both the
      succinylase and dehydrogenase pathways for m-DAP synthesis. In this study, we
      clone dapD and prove by enzyme experiments that this gene encodes the succinylase
      (M(r) = 24082), initiating the succinylase pathway of m-DAP synthesis. By using
      gene-directed mutation, dapD, as well as dapE encoding the desuccinylase, was
      inactivated, thereby forcing C. glutamicum to use only the dehydrogenase pathway
      of m-DAP synthesis. The mutants are unable to grow on organic nitrogen sources.
      When supplied with low ammonium concentrations but excess carbon, their
      morphology is radically altered and they are less resistant to mechanical stress
      than the wild type. Since the succinylase has a high affinity toward its
      substrate and uses glutamate as the nitrogen donor, while the dehydrogenase has a
      low affinity and incorporates ammonium directly, the m-DAP synthesis is another
      example of twin activities present in bacteria for access to important
      metabolites such as the well-known twin activities for the synthesis of glutamate
      or for the uptake of potassium.

PMID- 9620967
TI  - OpaR, a homolog of Vibrio harveyi LuxR, controls opacity of Vibrio
      parahaemolyticus.
AB  - Vibrio parahaemolyticus is an organism well adapted to communal life on surfaces.
      When grown on a surface or in a viscous layer, the bacterium induces a large gene
      system and differentiates to swarmer cells capable of movement over and
      colonization of surfaces. V. parahaemolyticus displays additional phenotypic
      versatility manifested as variable colony morphology, switching between
      translucent and opaque colony types. Although not itself luminescent, V.
      parahaemolyticus produces autoinducer molecules capable of inducing luminescence
      in Vibrio harveyi. To examine the role of quorum signaling in the lifestyles of
      V. parahaemolyticus, the functional homolog of the gene encoding the V. harveyi
      autoinducer-controlled transcriptional regulatory protein LuxR was cloned.
      Sequence analysis of the clone predicted an open reading frame with a deduced
      product 96% identical to LuxR. Introduction of the clone carrying the luxR-like
      locus into V. parahaemolyticus dramatically affected colony morphology,
      converting a translucent strain to an opaque one. When the coding sequence for
      the luxR homolog was placed under the control of the Ptac promoter, conversion to
      the opaque phenotype became inducible by isopropyl-beta-D-thiogalactopyranoside.
      Allelic disruption of the luxR-like gene on the chromosome of an opaque strain
      produced a translucent strain proficient in swarming ability. Primer extension
      mapping demonstrated opaR transcription in opaque but not translucent cell types.
      It is postulated that this gene, which has been named opaR, encodes a
      transcription factor controlling cell type. The underlying genetic basis for
      opaque-translucent variation may be the consequence of a genomic alteration
      detected in the opaR locus of opaque and translucent strains.

PMID- 9620968
TI  - Multiple transcriptional control of the Lactococcus lactis trp operon.
AB  - The Lactococcus lactis trpEGDCFBA operon is preceded by a noncoding leader
      region. Transcriptional studies of the trp operon revealed three transcripts with
      respective sizes of 8 kb (encompassing the entire operon), 290 bases, and 160
      bases (corresponding to parts of the leader region). These transcripts most
      likely result from initiation at the unique Ptrp promoter, transcription
      termination at either T1 (upstream of the trp operon) or T2 (downstream of the
      trp operon), and/or processing. Three parameters were shown to differentially
      affect the amount of these transcripts: (i) following tryptophan depletion, the
      amount of the 8-kb transcript increases 300- to 500-fold; (ii) depletion in any
      amino acid increased transcription initiation about fourfold; and (iii) upon
      entry into stationary phase the amount of the 8-kb transcript decreases abruptly.
      The tryptophan-dependent transcription control is exerted through transcription
      antitermination.

PMID- 9620969
TI  - Regulation of agr-dependent virulence genes in Staphylococcus aureus by RNAIII
      from coagulase-negative staphylococci.
AB  - Many of the genes coding for extracellular toxins, enzymes, and cell surface
      proteins in Staphylococcus aureus are regulated by a 510-nucleotide (nt) RNA
      molecule, RNAIII. Transcription of genes encoding secreted toxins and enzymes,
      including hla (alpha-toxin), saeB (enterotoxin B), tst (toxic shock syndrome
      toxin 1), and ssp (serine protease), is stimulated, while transcription of genes
      encoding cell surface proteins, like spa (protein A) and fnb (fibronectin binding
      proteins), is repressed. Besides being a regulator, RNAIII is also an mRNA coding
      for staphylococcal delta-lysin. We have identified RNAIII homologs in three
      different coagulase-negative staphylococci (CoNS), i.e., Staphylococcus
      epidermidis, Staphylococcus simulans, and Staphylococcus warneri. RNAIII from
      these CoNS turned out to be very similar to that of S. aureus and contained open
      reading frames encoding delta-lysin homologs. Though a number of big insertions
      and/or deletions have occurred, mainly in the 5' half of the molecules, the
      sequences show a high degree of identity, especially in the first 50 and last 150
      nt. The CoNS RNAIII had the ability to completely repress transcription of
      protein A in an RNAIII-deficient S. aureus mutant and the ability to stimulate
      transcription of the alpha-toxin and serine protease genes. However, the
      stimulatory effect was impaired compared to that of S. aureus RNAIII, suggesting
      that these regulatory functions are independent. By creating S. epidermidis-S.
      aureus RNAIII hybrids, we could also show that both the 5' and 3' halves of the
      RNAIII molecule are involved in the transcriptional regulation of alpha-toxin and
      serine protease mRNAs in S. aureus.

PMID- 9620970
TI  - Characterization of the hcnABC gene cluster encoding hydrogen cyanide synthase
      and anaerobic regulation by ANR in the strictly aerobic biocontrol agent
      Pseudomonas fluorescens CHA0.
AB  - The secondary metabolite hydrogen cyanide (HCN) is produced by Pseudomonas
      fluorescens from glycine, essentially under microaerophilic conditions. The
      genetic basis of HCN synthesis in P. fluorescens CHA0 was investigated. The
      contiguous structural genes hcnABC encoding HCN synthase were expressed from the
      T7 promoter in Escherichia coli, resulting in HCN production in this bacterium.
      Analysis of the nucleotide sequence of the hcnABC genes showed that each HCN
      synthase subunit was similar to known enzymes involved in hydrogen transfer,
      i.e., to formate dehydrogenase (for HcnA) or amino acid oxidases (for HcnB and
      HcnC). These similarities and the presence of flavin adenine dinucleotide- or
      NAD(P)-binding motifs in HcnB and HcnC suggest that HCN synthase may act as a
      dehydrogenase in the reaction leading from glycine to HCN and CO2. The hcnA
      promoter was mapped by primer extension; the -40 sequence (TTGGC ... ATCAA)
      resembled the consensus FNR (fumarate and nitrate reductase regulator) binding
      sequence (TTGAT ... ATCAA). The gene encoding the FNR-like protein ANR (anaerobic
      regulator) was cloned from P. fluorescens CHA0 and sequenced. ANR of strain CHA0
      was most similar to ANR of P. aeruginosa and CydR of Azotobacter vinelandii. An
      anr mutant of P. fluorescens (CHA21) produced little HCN and was unable to
      express an hcnA-lacZ translational fusion, whereas in wild-type strain CHA0,
      microaerophilic conditions strongly favored the expression of the hcnA-lacZ
      fusion. Mutant CHA21 as well as an hcn deletion mutant were impaired in their
      capacity to suppress black root rot of tobacco, a disease caused by Thielaviopsis
      basicola, under gnotobiotic conditions. This effect was most pronounced in water
      saturated artificial soil, where the anr mutant had lost about 30% of disease
      suppression ability, compared with wild-type strain CHA0. These results show that
      the anaerobic regulator ANR is required for cyanide synthesis in the strictly
      aerobic strain CHA0 and suggest that ANR-mediated cyanogenesis contributes to the
      suppression of black root rot.

PMID- 9620971
TI  - Transcriptional regulation of Alcaligenes eutrophus hydrogenase genes.
AB  - Alcaligenes eutrophus H16 produces a soluble hydrogenase (SH) and a membrane
      bound hydrogenase (MBH) which catalyze the oxidation of H2, supplying the
      organism with energy for autotrophic growth. The promoters of the structural
      genes for the SH and the MBH, PSH and PMBH, respectively, were identified by
      means of the primer extension technique. Both promoters were active in vivo under
      hydrogenase-derepressing conditions but directed only low levels of transcription
      under condition which repressed hydrogenase synthesis. The cellular pools of SH
      and MBH transcripts under the different growth conditions correlated with the
      activities of the respective promoters. Also, an immediate and drastic increase
      in transcript pool levels occurred upon derepression of the hydrogenase system.
      Both promoters were dependent on the minor sigma factor sigma 54 and on the
      hydrogenase regulator HoxA in vivo. PSH was stronger than PMBH under both
      heterotrophic and autotrophic growth conditions. The two promoters were induced
      at approximately the same rates upon derepression of the hydrogenase system in
      diauxic cultures. The response regulator HoxA mediated low-level activation of
      PSH and PMBH in a heterologous system.

PMID- 9620972
TI  - Effects of carbon source on expression of F0 genes and on the stoichiometry of
      the c subunit in the F1F0 ATPase of Escherichia coli.
AB  - Expression of the genes for the membrane-bound F0 sector of the Escherichia coli
      F1F0 proton-translocating ATPase can respond to changes in metabolic conditions,
      and these changes are reflected in alterations in the subunit stoichiometry of
      the oligomeric F0 proton channel. Transcriptional and translational lacZ fusions
      to the promoter and to two F0 genes show that, during growth on the
      nonfermentable carbon source succinate, transcription of the operon and
      translation of uncB, encoding the a subunit of F0, are higher than during growth
      on glucose. In contrast, translation of the uncE gene, encoding the c subunit of
      F0, is higher during growth on glucose than during growth on succinate.
      Translation rates of both uncB and uncE change as culture density increases, but
      transcription rates do not. Quantitation of the c stoichiometry shows that more c
      subunits are assembled into the F1F0 ATPase in cells grown on glucose than in
      cells grown on succinate. E. coli therefore appears to have a mechanism for
      regulating the composition and, presumably, the function of the ATPase in
      response to metabolic circumstances.

PMID- 9620973
TI  - Cloning and comparison of fliC genes and identification of glycosylation in the
      flagellin of Pseudomonas aeruginosa a-type strains.
AB  - Pseudomonas aeruginosa a-type strains produce flagellin proteins which vary in
      molecular weight between strains. To compare the properties of a-type flagellins,
      the flagellin genes of several Pseudomonas aeruginosa a-type strains, as
      determined by interaction with specific anti-a monoclonal antibody, were cloned
      and sequenced. PCR amplification of the a-type flagellin gene fragments from five
      strains each yielded a 1.02-kb product, indicating that the gene size is not
      likely to be responsible for the observed molecular weight differences among the
      a-type strains. The flagellin amino acid sequences of several a-type strains
      (170,018, 5933, 5939, and PAK) were compared, and that of 170,018 was compared
      with that of PAO1, a b-type strain. The former comparisons revealed that a-type
      strains are similar in amino acid sequence, while the latter comparison revealed
      differences between 170,018 and PAO1. Posttranslational modification was explored
      for its contribution to the observed differences in molecular weight among the a
      type strains. A biotin-hydrazide glycosylation assay was performed on the
      flagellins of three a-type strains (170,018, 5933, and 5939) and one b-type
      strain (M2), revealing a positive glycosylation reaction for strains 5933 and
      5939 and a negative reaction for 170,018 and M2. Deglycosylation of the flagellin
      proteins with trifluoromethanesulfonic acid (TFMS) confirmed the glycosylation
      results. A molecular weight shift was observed by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis analysis for the TFMS-treated flagellins of
      5933 and 5939. These results indicate that the molecular weight discrepancies
      observed for the a-type flagellins can be attributed, at least in part, to
      glycosylation of the protein. Anti-a flagellin monoclonal antibody reacted with
      the TFMS-treated flagellins, suggesting that the glycosyl groups are not a
      necessary component of the epitope for the human anti-a monoclonal antibody.
      Comparisons between a-type sequences and a b-type sequence (PAO1) will aid in
      delineation of the epitope for this monoclonal antibody.

PMID- 9620974
TI  - The MTCY428.08 gene of Mycobacterium tuberculosis codes for NAD+ synthetase.
AB  - The product of the MTCY428.08 gene of Mycobacterium tuberculosis shows sequence
      homology with several NAD+ synthetases. The MTCY428.08 gene was cloned into the
      expression vectors pGEX-4T-1 and pET-15b. Expression in Escherichia coli led to
      overproduction of glutathione S-transferase fused and His6-tagged gene products,
      which were enzymatically assayed for NAD synthetase activity. Our results
      demonstrate that the MTCY428.08 gene of M. tuberculosis is the structural gene
      for NAD+ synthetase.

PMID- 9620975
TI  - The glucose kinase of Bacillus subtilis.
AB  - The open reading frame yqgR (now termed glcK), which had been sequenced as part
      of the genome project, encodes a glucose kinase of Bacillus subtilis. A 1.1-kb
      DNA fragment containing glcK complemented an Escherichia coli strain deficient in
      glucose kinase activity. Insertional mutagenesis of glcK resulted in a complete
      inactivation of glucose kinase activity in crude protein extracts, indicating
      that B. subtilis contains one major glucose kinase. The glcK gene encodes a 321
      residue protein with a molecular mass of 33.5 kDa. The glucose kinase was
      overexpressed as a fusion protein to a six-His affinity tag and purified to
      homogeneity. The enzyme had K(m) values for ATP and glucose of 0.77 and 0.24 mM,
      respectively, and a Vmax of 93 mumol min-1 mg-1. A B. subtilis strain deficient
      for glucose kinase grew at the same rate on different carbon sources tested,
      including disaccharides such as maltose, trehalose, and sucrose.

PMID- 9620976
TI  - Cloning, sequencing, and characterization of the recA gene from Rhodopseudomonas
      viridis and construction of a recA strain.
AB  - A recombination-deficient strain of the phototrophic bacterium Rhodopseudomonas
      viridis was constructed for the homologous expression of modified photosynthetic
      reaction center genes. The R. viridis recA gene was cloned and subsequently
      deleted from the R. viridis genome. The cloned R. viridis recA gene shows high
      identity to known recA genes and was able to complement the Rec- phenotype of a
      Rhizobium meliloti recA strain. The constructed R. viridis recA strain showed the
      general Rec- phenotype, i.e., increased sensitivity to DNA damage and severely
      impaired recombination ability. The latter property of this strain will be of
      advantage in particular for expression of modified, nonfunctional photosynthetic
      reaction centers which are not as yet available.

PMID- 9620977
TI  - The Arcanobacterium (Actinomyces) pyogenes plasmid pAP1 is a member of the
      pIJ101/pJV1 family of rolling circle replication plasmids.
AB  - The 2.4-kb plasmid pAP1 from Arcanobacterium (Actinomyces) pyogenes had sequence
      similarity within the putative replication protein and double-stranded origin
      with the pIJ101/pJV1 family of plasmids. pJGS84, a derivative of pAP1 containing
      a kanamycin resistance gene, was able to replicate in Escherichia coli and
      Corynebacterium pseudotuberculosis, as well as in A. pyogenes. Detection of
      single-stranded DNA intermediates of pJGS84 replication suggested that this
      plasmid replicates by the rolling circle mechanism.

PMID- 9620978
TI  - An autonomously replicating transforming vector for Sulfolobus solfataricus.
AB  - A plasmid able to transform and to be stably maintained both in Sulfolobus
      solfataricus and in Escherichia coli was constructed by insertion into an E. coli
      plasmid of the autonomously replicating sequence of the virus particle SSV1 and a
      suitable mutant of the hph (hygromycin phosphotransferase) gene as the
      transformation marker. The vector suffered no rearrangement and/or chromosome
      integration, and its copy number in Sulfolobus was increased by exposure of the
      cells to mitomycin C.

PMID- 9620979
TI  - Streptomyces griseus protease B: secretion correlates with the length of the
      propeptide.
AB  - Streptomyces griseus protease B, a member of the chymotrypsin superfamily, is
      encoded by a gene that express a pre-pro-mature protein. During secretion the
      precursor protein is processed into a mature, fully folded protease. In this
      study, we constructed a family of genes which encode deletions at the amino
      terminal end of the propeptide. The secretion of active protease B was seen to
      decrease in an exponential manner according to the length of the deletion. The
      results underscore the intimate relationship between folding and secretion in
      bacterial protease expression. They further suggest that the propeptide segment
      of the zymogen stabilizes the folding of the mature through many small binding
      interactions over the entire surface of the peptide rather than through a few
      specific contacts.

PMID- 9620980
TI  - Appropriate expression of filamentous phage f1 DNA replication genes II and X
      requires RNase E-dependent processing and separate mRNAs.
AB  - The products of in-frame overlapping genes II and X carried by the filamentous
      phage f1 genome are proteins with required but opposing functions in phage DNA
      replication. Their normal relative levels are important for continuous production
      of phage DNA without killing infected Escherichia coli hosts. Here we identify
      several factors responsible for determining the relative levels of pII and pX and
      that, if perturbed, alter the normal distribution of the phage DNA species in
      infected hosts. Translation of the two proteins is essentially relegated to
      separate mRNAs. The mRNAs encoding genes II and X are also differentially
      sensitive to cleavage dependent on rne, the gene encoding the only E. coli endo
      RNase known to have a global role in mRNA stability. Whereas pII levels are
      limited at the level of mRNA stability, normal pX levels require transcription in
      sufficient amounts from the promoter for the smaller mRNA encoding only pX.

PMID- 9620981
TI  - The Bacillus subtilis AraE protein displays a broad substrate specificity for
      several different sugars.
AB  - Bacillus subtilis 168 is unable to grow on xylose and galactose as sole carbon
      sources, owing to the lack of specific transporters. We show that they are
      imported into the cell by the activity of AraE, an arabinose transporter whose
      synthesis is induced by L-arabinose.

PMID- 9620982
TI  - The FixK2 protein is involved in regulation of symbiotic hydrogenase expression
      in Bradyrhizobium japonicum.
AB  - The roles of the nitrogen fixation regulatory proteins NifA, FixK1, and FixK2 in
      the symbiotic regulation of hydrogenase structural gene expression in
      Bradyrhizobium japonicum have been investigated. Bacteroids from FixJ and FixK2
      mutants have little or no hydrogenase activity, and extracts from these mutant
      bacteroids contain no hydrogenase protein. Bacteroids from a FixK1 mutant exhibit
      wild-type levels of hydrogenase activity. In beta-galactosidase transcriptional
      assays with NifA and FixK2 expression plasmids, the FixK2 protein induces
      transcription from the hup promoter to levels similar to those induced by HoxA,
      the transcriptional activator of free-living hydrogenase expression. The NifA
      protein does not activate transcription at the hydrogenase promoter. Therefore,
      FixK2 is involved in the transcriptional activation of symbiotic hydrogenase
      expression. By using beta-galactosidase transcriptional fusion constructs
      containing successive truncations of the hup promoter, the region of the hup
      promoter required for regulation by FixK2 was determined to be between 29 and 44
      bp upstream of the transcription start site.

PMID- 9620983
TI  - Activation of bacteriophage Mu mom transcription by C protein does not require
      specific interaction with the carboxyl-terminal region of the alpha or sigma 70
      subunit of Escherichia coli RNA polymerase.
AB  - Late in its growth cycle, transcription of the phage Mu mom Promoter (Pmom) is
      activated by the phage gene product, C, a site-specific DNA binding protein. In
      vitro transcription analyses showed that this activation does not require
      specific contacts between C and the carboxyl-terminal region of the alpha or
      sigma 70 subunit of Escherichia coli RNA polymerase. Unexpectedly, these results
      are in contrast to those known for another Mu-encoded transcriptional activator,
      Mor, which has a high degree of sequence identity with C and appears to interact
      with the carboxyl termini of both alpha and sigma 70.

PMID- 9620984
TI  - Characterization of the glnK-amtB operon of Azotobacter vinelandii.
AB  - To determine whether in Azotobacter vinelandii the PII protein influences the
      regulation of nif gene expression in response to fluxes in the ammonium supply,
      the gene encoding PII was isolated and characterized. Its deduced translation
      product was highly similar to PII proteins from other organisms, with the
      greatest degree of relatedness being exhibited to the Escherichia coli glnK gene
      product. A gene designated amtB was found downstream of and was contranscribed
      with glnK as in E. coli. The AmtB protein is similar to functionally
      characterized ammonium transport proteins from a few other eukaryotes and one
      other prokaryote. glnK and amtB comprise an operon. Attempts to isolate a stable
      glnK mutant strain were unsuccessful, suggesting that glnK, like glnA, is an
      essential gene in A. vinelandii. amtB mutants were isolated, and although growth
      on limiting amounts of ammonium was similar in the mutant and wild-type strains,
      the mutants were unable to transport [14C]methylammonium.

PMID- 9620985
TI  - Polyomavirus T antigens: molecular chaperones for multiprotein complexes.

PMID- 9620986
TI  - Archetype JC virus efficiently replicates in COS-7 cells, simian cells
      constitutively expressing simian virus 40 T antigen.
AB  - JC polyomavirus (JCV), the causative agent of progressive multifocal
      leukoencephalopathy (PML), is ubiquitous in humans, infecting children
      asymptomatically and then persisting in the kidney. Renal JCV is not latent but
      replicates to excrete progeny in the urine. The renal-urinary JCV DNAs carry the
      archetype regulatory region that generates various rearranged regulatory regions
      occurring in JCVs derived from the brains of PML patients. Tissue cultures that
      support the efficient growth of archetype JCV have not been reported. We studied
      whether archetype JCV could replicate in COS-7 cells, simian cells transformed
      with an origin-defective mutant of simian virus 40 (SV40). Efficient JCV
      replication, as detected by a hemagglutination assay, was observed in cultures
      transfected with five of the six archetype DNAs. The progeny JCVs could be
      passaged to fresh COS-7 cells. However, when the parental cells of COS-7 not
      expressing T antigen were transfected with archetype JCV DNAs, no viral
      replication was detected, indicating that SV40 T antigen is essential for the
      growth of JCV in COS-7 cells. The archetype regulatory region was conserved
      during viral growth in COS-7 cells, although a small proportion of JCV DNAs
      underwent rearrangements outside the regulatory region. We then attempted to
      recover archetype JCV from urine by viral culture in COS-7 cells. Efficient JCV
      production was observed in COS-7 cells infected with five of the six JCV-positive
      urine samples examined. Thus, COS-7 cells should be of use not only for the
      production of archetype JCV on a large scale but also for the isolation of
      archetype JCV from urine.

PMID- 9620987
TI  - The latent herpes simplex virus type 1 genome copy number in individual neurons
      is virus strain specific and correlates with reactivation.
AB  - The viral genetic elements that determine the in vivo reactivation efficiencies
      of fully replication competent wild-type herpes simplex virus (HSV) strains have
      not been identified. Among the common laboratory strains, KOS reactivates in vivo
      at a lower efficiency than either strain 17syn+ or strain McKrae. An important
      first step in understanding the molecular basis for this observation is to
      distinguish between viral genetic factors that regulate the establishment of
      latency from those that directly regulate reactivation. Reported here are
      experiments performed to determine whether the reduced reactivation of KOS was
      associated with a reduced ability to establish or maintain latent infections. For
      comparative purposes, latent infections were quantified by (i) quantitative PCR
      on DNA extracted from whole ganglia, (ii) the number of latency-associated
      transcript (LAT) promoter-positive neurons, using KOS and 17syn+ LAT promoter
      beta-galactosidase reporter mutants, and (iii) contextual analysis of DNA. Mice
      latently infected with 17syn+-based strains contained more HSV type 1 (HSV-1) DNA
      in their ganglia than those infected with KOS strains, but this difference was
      not statistically significant. The number of latently infected neurons also did
      not differ significantly between ganglia latently infected with either the low-
      or high-reactivator strains. In addition to the number of latent sites, the
      number of viral genome copies within the individual latently infected neurons has
      recently been demonstrated to be variable. Interestingly, neurons latently
      infected with KOS contained significantly fewer viral genome copies than those
      infected with either 17syn+ or McKrae. Thus, the HSV-1 genome copy number profile
      is viral strain specific and positively correlates with the ability to reactivate
      in vivo. This is the first demonstration that the number of HSV genome copies
      within individual latently infected neurons is regulated by viral genetic
      factors. These findings suggest that the latent genome copy number may be an
      important parameter for subsequent induced reactivation in vivo.

PMID- 9620988
TI  - In vivo immune evasion mediated by the herpes simplex virus type 1 immunoglobulin
      G Fc receptor.
AB  - Herpes simplex virus (HSV) glycoproteins gE and gI form an immunoglobulin G (IgG)
      Fc receptor (FcgammaR) that binds the Fc domain of human anti-HSV IgG and
      inhibits Fc-mediated immune functions in vitro. gE or gI deletion mutant viruses
      are avirulent, probably because gE and gI are also involved in cell-to-cell
      spread. In an effort to modify FcgammaR activity without affecting other gE
      functions, we constructed a mutant virus, NS-gE339, that has four amino acids
      inserted into gE within the domain homologous to mammalian IgG FcgammaRs. NS
      gE339 expresses gE and gI, is FcgammaR-, and does not participate in antibody
      bipolar bridging since it does not block activities mediated by the Fc domain of
      anti-HSV IgG. In vivo studies were performed with mice because the HSV-1 FcgammaR
      does not bind murine IgG; therefore, the absence of an FcgammaR should not affect
      virulence in mice. NS-gE339 causes disease at the skin inoculation site
      comparably to wild-type and rescued viruses, indicating that the FcgammaR- mutant
      virus is pathogenic in animals. Mice were passively immunized with human anti-HSV
      IgG and then infected with mutant or wild-type virus. We postulated that the HSV
      1 FcgammaR should protect wild-type virus from antibody attack. Human anti-HSV
      IgG greatly reduced viral titers and disease severity in NS-gE339-infected
      animals while having little effect on wild-type or rescued virus. We conclude
      that the HSV-1 FcgammaR enables the virus to evade antibody attack in vivo, which
      likely explains why antibodies are relatively ineffective against HSV infection.

PMID- 9620989
TI  - Role for beta2-microglobulin in echovirus infection of rhabdomyosarcoma cells.
AB  - A monoclonal antibody (MAb) that blocks most echoviruses (EVs) from infecting
      rhabdomyosarcoma (RD) cells has been isolated. By using the CELICS cloning method
      (T. Ward, P. A. Pipkin, N. A. Clarkson, D. M. Stone, P. D. Minor, and J. W.
      Almond, EMBO J. 13:5070-5074, 1994), the ligand for this antibody has been
      identified as beta2-microglobulin (beta2m), the 12-kDa protein that associates
      with class I heavy chains to form class I HLA complexes. A commercial MAb (MAb
      1350) against beta2m was also found to block EV7 infection without affecting
      binding to its receptor, DAF, or replication of EV7 viral RNA inside cells. Entry
      of EV7 into cells was reduced by only 30% by antibody and cytochalasin D, an
      inhibitor of endocytosis mediated by caveolae and clathrin-coated pits, but was
      not significantly reduced by sodium azide. The block to virus entry by
      cytochalasin D was additive to the block induced by antibody. We suggest that EV7
      rapidly enters into a multicomponent receptor complex prior to entry into cells
      and that this initial entry event requires beta2m or class I HLA for infection to
      proceed.

PMID- 9620990
TI  - Characterization of the cytolytic T-lymphocyte response to a candidate vaccine
      strain of equine herpesvirus 1 in CBA mice.
AB  - The cytolytic T-lymphocyte (CTL) response to respiratory infection with equine
      herpesvirus 1 (EHV-1) in CBA (H-2(k)) mice was investigated. Intranasal (i.n.)
      inoculation of mice with the attenuated EHV-1 strain KyA resulted in the
      generation of a primary virus-specific CTL response in the draining mediastinal
      lymph nodes 5 days following infection. EHV-1-specific CTL could be restimulated
      from the spleen up to 26 weeks after the resolution of infection, indicating that
      a long-lived memory CTL population was generated. Depletion of CD8+ T cells by
      treatment with antibody and complement prior to assay eliminated CTL activity
      from both primary and memory populations, indicating that cytolytic activity in
      this model was mediated by class I major histocompatibility complex-restricted,
      CD8+ T cells. A single i.n. inoculation with KyA induced protective immunity
      against infection with the pathogenic EHV-1 strain, RacL11. The adoptive transfer
      of splenocytes from KyA-immune donors into sublethally irradiated recipients
      resulted in a greater than 250-fold reduction in RacL11 in the lung. The
      elimination of both CD4+ and CD8+ T cells from the transferred cells abrogated
      clearance of RacL11, while the selective depletion of either subpopulation alone
      had little effect. These results suggested that both lymphocyte subpopulations
      contribute to viral clearance, with either subpopulation alone being sufficient.

PMID- 9620992
TI  - Characterization of the proline-rich region of murine leukemia virus envelope
      protein.
AB  - Mammalian type C retroviral envelope proteins contain a variable proline-rich
      region (PRR), located between the N-terminal receptor-binding domain and the more
      highly conserved C-terminal portion of the surface (SU) subunit. We have
      investigated the role of the PRR in the function of murine leukemia virus (MuLV)
      envelope protein. In the MuLVs, the PRR contains a highly conserved N-terminal
      sequence and a hypervariable C-terminal sequence. Despite this variability, the
      amphotropic PRR could functionally substitute for the ecotropic PRR. The
      hypervariable region of the PRR was not absolutely required for envelope protein
      function. However, truncations in this region resulted in decreased levels of
      both the SU and TM proteins in viral particles and increased amounts of the
      uncleaved precursor protein, Pr85. In contrast, the N-terminal conserved region
      was essential for viral infectivity. Deletion of this region prevented the stable
      incorporation of envelope proteins into viral particles in spite of normal
      envelope protein processing, wild-type levels of cell surface expression, and a
      wild-type ability to induce syncytia in an XC cell cocultivation assay. However,
      higher levels of the SU protein were shed into the supernatant, suggesting a
      defect in SU-TM interactions. Our data are most consistent with a role for the
      PRR in stabilizing the overall structure of the protein, thereby affecting the
      proper processing of Pr85, SU-TM interactions, and the stable incorporation of
      envelope proteins into viral particles. In addition, we have demonstrated that
      the PRR can tolerate the insertion of a peptide-binding domain, making this a
      potentially useful site for constructing targetable retroviral vectors.

PMID- 9620991
TI  - Characterization of a nerve growth factor-inducible cellular activity that
      enhances herpes simplex virus type 1 gene expression and replication of an ICP0
      null mutant in cells of neural lineage.
AB  - Herpes simplex virus type 1 (HSV-1) ICP0 is required for efficient viral gene
      expression during lytic infection, especially at low multiplicities. A series of
      cellular activities that can substitute for ICP0 has been identified, suggesting
      that when the activity of ICP0 is limiting, these activities can substitute for
      ICP0 to activate viral gene expression. The cellular activities may be especially
      important during reactivation of HSV from neuronal latency when viral gene
      expression is initiated in the absence of prior viral protein synthesis.
      Consistent with this hypothesis, we have identified an inducible activity in
      cells of neural lineage (PC12) that can complement the low-multiplicity growth
      phenotype of an ICP0 null mutant, n212. Pretreatment of PC12 cells with nerve
      growth factor (NGF) or fibroblast growth factor (FGF) prior to infection produced
      a 10- to 20-fold increase in the 24-h yield of n212 but only a 2- to 4-fold
      increase in the yield of wild-type virus relative to mock treatment. Slot blot
      analysis of nuclear DNA isolated from infected cells treated or mock treated with
      NGF indicated that NGF treatment does not significantly affect viral entry. The
      NGF-induced activity in PC12 cells was expressed transiently, with peak
      complementing activity observed when cells were treated with NGF 12 h prior to
      infection. Addition of NGF 3 h after infection had little effect on virus yield.
      The NGF-induced cellular activity was inhibited by pretreatment of PC12 cells
      with kinase inhibitors that have high specificity for kinases involved in NGF/FGF
      dependent signal transduction. RNase protection assays demonstrated that the NGF
      inducible PC12 cell activity, like that of ICP0, functions to increase the level
      of viral mRNA during low-multiplicity infection. These results suggest that
      activation of viral transcription by ICP0 and transcriptional activation of
      cellular genes by NGF and FGF utilize common signal transduction pathways in PC12
      cells.

PMID- 9620993
TI  - Functional domains in the retroviral transmembrane protein.
AB  - The envelope glycoproteins of the mammalian type C retroviruses consist of two
      subunits, a surface (SU) protein and a transmembrane (TM) protein. SU binds to
      the viral receptor and is thought to trigger conformational changes in the
      associated TM protein that ultimately lead to the fusion of viral and host cell
      membranes. For Moloney murine leukemia virus (MoMuLV), the envelope protein
      probably exists as a trimer. We have previously demonstrated that the
      coexpression of envelope proteins that are individually defective in either the
      SU or TM subunits can lead to functional complementation (Y. Zhao et al., J.
      Virol. 71:6967-6972, 1997). We have now extended these studies to investigate the
      abilities of a panel of fusion-defective TM mutants to complement each other.
      This analysis identified distinct complementation groups within TM, with
      implications for interactions between different regions of TM in the fusion
      process. In viral particles, the C-terminal 16 amino acids of the MoMuLV TM (the
      R peptide) are cleaved by the viral protease, resulting in an increased
      fusogenicity of the envelope protein. We have examined the consequences of R
      peptide cleavage for the different TM fusion mutants and have found that this
      enhancement of fusogenicity can only occur in cis to certain of the TM mutants.
      These results suggest that R peptide cleavage enhances the fusogenicity of the
      envelope protein by influencing the interaction of two distinct regions in the TM
      ectodomain.

PMID- 9620994
TI  - Identification of replication-competent strains of simian immunodeficiency virus
      lacking multiple attachment sites for N-linked carbohydrates in variable regions
      1 and 2 of the surface envelope protein.
AB  - Carbohydrates comprise about 50% of the mass of gp120, the external envelope
      glycoprotein of simian immunodeficiency virus (SIV) and human immunodeficiency
      virus. We identified 11 replication-competent derivatives of SIVmac239 lacking
      two, three, four, or five potential sites for N-linked glycosylation. These sites
      were located within and around variable regions 1 and 2 of the surface envelope
      protein of the virus. Asn (AAT) of the canonical N-linked glycosylation
      recognition sequence (Asn X Ser/Thr) was changed in each case to the structurally
      similar Gln (CAG or CAA) such that two nucleotide changes in the codon would be
      required for reversion. Replication of one triple mutant (g456), however, was
      severely impaired. A revertant of the g456 mutant was recovered from CEMx174
      cells with a Met-to-Val compensatory substitution at position 144, 2 amino acids
      upstream of attachment site 5. Thus, a debilitating loss of sites for N-linked
      glycosylation can be compensated for by amino acid changes not involving the Asn
      X-Ser/Thr consensus motif. These results provide a framework to begin testing the
      hypothesis that carbohydrates form a barrier that can limit the humoral immune
      responses to the virus.

PMID- 9620995
TI  - Nonreciprocal pseudotyping: murine leukemia virus proteins cannot efficiently
      package spleen necrosis virus-based vector RNA.
AB  - It has been documented that spleen necrosis virus (SNV) can package murine
      leukemia virus (MLV) RNA efficiently and propagate MLV vectors to the same titers
      as it propagates SNV-based vectors. Although the SNV packaging signal (E) and MLV
      packaging signal (Psi) have little sequence homology, similar double-hairpin RNA
      structures were predicted and supported by experimental evidence. To test whether
      SNV RNA can be packaged by MLV proteins, we modified an SNV vector to be
      expressed in an MLV-based murine helper cell line. Surprisingly, we found that
      MLV proteins could not support the replication of SNV vectors. The decrease in
      titer was approximately 2,000- to 20,000-fold in one round of retroviral
      replication. RNA analysis revealed that SNV RNA was not efficiently packaged by
      MLV proteins. RNA hybridization of the cellular and viral RNAs indicated that SNV
      RNA was packaged at least 25-fold less efficiently than MLV RNA, which was the
      sensitivity limit of the hybridization assay. The contrast between the MLV and
      SNV packaging specificity is striking. SNV proteins can recognize both SNV E and
      MLV Psi, but MLV can recognize only MLV Psi. This is the first demonstration of
      two retroviruses with nonreciprocal packaging specificities.

PMID- 9620996
TI  - Threshold number of provirus copies required per cell for efficient virus
      production and interference in moloney murine leukemia virus-infected NIH 3T3
      cells.
AB  - The gag-pol readthrough mutant of Moloney murine leukemia virus, MLV-B(CAG) (T.
      Odawara, H. Yoshikura, M. Oshima, T. Tanaka, D. S. Jones, F. Nemoto, Y. Kuchino,
      and A. Iwamoto, J. Virol. 65:6376-6379, 1991), was poorly complemented by a
      mutant encoding only Gag. This is because with all the genetic elements necessary
      for env expression present in MLV-B(CAG), insufficient Env protein was produced
      by the cells expressing MLV-B(CAG) for efficient virus production. Since the env
      mRNA expression per provirus in the MLV-B(CAG)- and wild-type-MLV-producing cells
      were the same and since the cells expressing the former contained eightfold fewer
      proviral copies, the insufficient Env expression by the former was found to be
      due to insufficient proviral copies in the cells. Examination of the cell clones
      having various proviral copies of Deltawt MLV (M. Oshima, T. Odawara, T. Matano,
      H. Sakahira, Y. Kuchino, A. Iwamoto, and H. Yoshikura, J. Virol. 70:2286-2295,
      1996) showed that mRNA level was proportional to the number of proviral copies
      while interference and virus production followed a sigmoid curve with a sharp
      rise at the threshold number of proviral copies of around four per cell.
      Multicycle infection probably continues until the threshold level of proviral
      copies is attained in natural infection too.

PMID- 9620997
TI  - Genetically divergent strains of human immunodeficiency virus type 2 use multiple
      coreceptors for viral entry.
AB  - Several members of the seven-transmembrane chemokine receptor family have been
      shown to serve, with CD4, as coreceptors for entry by human immunodeficiency
      virus type 1 (HIV-1). While coreceptor usage by HIV-1 primary isolates has been
      studied by several groups, there is only limited information available concerning
      coreceptor usage by primary HIV-2 isolates. In this study, we have analyzed
      coreceptor usage of 15 primary HIV-2 isolates, using lymphocytes from a donor
      with nonfunctional CCR5 (CCR5 -/-; homozygous 32-bp deletion). Based on the
      infections of PBMCs, seven of these primary isolates had an absolute requirement
      for CCR5 expression, whereas the remaining eight exhibited a broader coreceptor
      usage. All CCR5-requiring isolates were non-syncytium inducing, whereas isolates
      utilizing multiple coreceptors were syncytium inducing. Blocking experiments
      using known ligands for chemokine receptors provided indirect evidence for
      additional coreceptor utilization by primary HIV-2 isolates. Analysis of GHOST4
      cell lines expressing various chemokine receptors (CCR1, CCR2b, CCR3, CCR4, CCR5,
      CXCR4, BONZO, and BOB) further defined specific coreceptor usage of primary HIV-2
      isolates. The receptors used included CXCR4, CCR1-5, and the recently described
      receptors BONZO and BOB. However, the efficiency at which the coreceptors were
      utilized varied greatly among the various isolates. Analysis of V3 envelope
      sequences revealed no specific motif that correlated with coreceptor usage. Our
      data demonstrate that primary HIV-2 isolates are capable of using a broad range
      of coreceptors for productive infection in vitro. Additionally, our data suggest
      that expanded coreceptor usage by HIV-2 may correlate with disease progression.

PMID- 9620998
TI  - Kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor.
AB  - Interferons (IFNs) are a family of multifunctional cytokines with antiviral
      activities. The K9 open reading frame of Kaposi's sarcoma-associated herpesvirus
      (KSHV) exhibits significant homology with cellular IFN regulatory factors (IRFs).
      We have investigated the functional consequence of K9 expression in IFN-mediated
      signal transduction. Expression of K9 dramatically repressed transcriptional
      activation induced by IFN-alpha, -beta, and -gamma. Further, it induced
      transformation of NIH 3T3 cells, resulting in morphologic changes, focus
      formation, and growth in reduced-serum conditions. The expression of antisense K9
      in KSHV-infected BCBL-1 cells consistently increased IFN-mediated transcriptional
      activation but drastically decreased the expression of certain KSHV genes. Thus,
      the K9 gene of KSHV encodes the first virus-encoded IRF (v-IRF) which functions
      as a repressor for cellular IFN-mediated signal transduction. In addition, v-IRF
      likely plays an important role in regulating KSHV gene expression. These results
      suggest that KSHV employs an unique mechanism to antagonize IFN-mediated
      antiviral activity by harboring a functional v-IRF.

PMID- 9620999
TI  - Virion-targeted viral inactivation of human immunodeficiency virus type 1 by
      using Vpr fusion proteins.
AB  - Inactivation of progeny virions with chimeric virion-associated proteins
      represents a novel therapeutic approach against human immunodeficiency virus
      (HIV) replication. The HIV type 1 (HIV-1) Vpr gene product, which is packaged
      into virions, is an attractive candidate for such a strategy. In this study, we
      developed Vpr-based fusion proteins that could be specifically targeted into
      mature HIV-1 virions to affect their structural organization and/or functional
      integrity. Two Vpr fusion proteins were constructed by fusing to the first 88
      amino acids of HIV-1 Vpr the chloramphenicol acetyltransferase enzyme (VprCAT) or
      the last 18 C-terminal amino acids of the HIV-1 Vpu protein (VprIE). These Vpr
      fusion proteins were initially designed to quantify their efficiency of
      incorporation into HIV-1 virions when produced in cis from the provirus.
      Subsequently, CD4+ Jurkat T-cell lines constitutively expressing the VprCAT or
      the VprIE fusion protein were generated with retroviral vectors. Expression of
      the VprCAT or the VprIE fusion protein in CD4+ Jurkat T cells did not interfere
      with cellular viability or growth but conferred substantial resistance to HIV
      replication. The resistance to HIV replication was more pronounced in Jurkat
      VprIE cells than in Jurkat-VprCAT cells. Moreover, the antiviral effect mediated
      by VprIE was dependent on an intact p6(gag) domain, indicating that the
      impairment of HIV-1 replication required the specific incorporation of Vpr fusion
      protein into virions. Gene expression, assembly, or release was not affected upon
      expression of these Vpr fusion proteins. Indeed, the VprIE and VprCAT fusion
      proteins were shown to affect the infectivity of progeny virus, since HIV virions
      containing the VprCAT or the VprIE fusion proteins were, respectively, 2 to 3
      times and 10 to 30 times less infectious than the wild-type virus. Overall, this
      study demonstrated the successful transfer of resistance to HIV replication in
      tissue cultures by use of Vpr-based antiviral genes.

PMID- 9621000
TI  - Transcription of hepatitis delta antigen mRNA continues throughout hepatitis
      delta virus (HDV) replication: a new model of HDV RNA transcription and
      replication.
AB  - Hepatitis delta virus (HDV) replicates by RNA-dependent RNA synthesis according
      to a double rolling circle model. Also synthesized during replication is a 0.8
      kb, polyadenylated mRNA encoding the hepatitis delta antigen (HDAg). It has been
      proposed that this mRNA species represents the initial product of HDV RNA
      replication; subsequent production of genomic-length HDV RNA relies on
      suppression of the HDV RNA polyadenylation signal by HDAg. However, this model
      was based on studies which required the use of an HDV cDNA copy to initiate HDV
      RNA replication in cell culture, thus introducing an artificial requirement for
      DNA-dependent RNA synthesis. We have now used an HDV cDNA-free RNA transfection
      system and a method that we developed to detect specifically the mRNA species
      transcribed from the HDV RNA template. We established that this polyadenylated
      mRNA is 0.8 kb in length and its 5' end begins at nucleotide 1631. Surprisingly,
      kinetic studies showed that this mRNA continued to be synthesized even late in
      the viral replication cycle and that the mRNA and the genomic-length RNA
      increased in parallel, even in the presence of HDAg. Thus, a switch from
      production of the HDAg mRNA to the full-length HDV RNA does not occur in this
      system, and suppression of the polyadenylation site by HDAg may not significantly
      regulate the synthesis of the HDAg mRNA, as previously proposed. These findings
      reveal novel insights into the mechanism of HDV RNA replication. A new model of
      HDV RNA replication and transcription is proposed.

PMID- 9621001
TI  - Characterization of the transcriptional repressive element of the human
      cytomegalovirus immediate-early US3 gene.
AB  - Transcriptional repression is utilized by human cytomegalovirus to regulate
      expression of the immediate-early US3 gene. Sequences located 3' of the US3 TATA
      box are required for down regulation of expression. Mutagenesis of US3 sequences
      identified a 10-nucleotide region that is essential for transcriptional
      repression. In addition to the 10-nucleotide element, an additional region, which
      includes the US3 initiator element, was needed to confer repression on a
      heterologous promoter. Thus, a 19-nucleotide element (-18 to +1 relative to the
      transcription start site) functioned as a transcriptional repressive element
      (tre). The tre repressed transcription in a position-dependent but orientation
      independent manner. In vivo footprinting experiments demonstrated that
      transcriptional repression is associated with a decrease in protein interactions
      with the US3 promoter and surrounding sequences. The data presented here suggest
      that the association of an as yet unidentified repressor protein with the tre
      represses transcription by inhibiting assembly of the transcription initiation
      complex on the US3 promoter.

PMID- 9621002
TI  - Preferential completion of human immunodeficiency virus type 1 proviruses
      initiated with tRNA3Lys rather than tRNA1,2Lys.
AB  - All retroviral genomes contain a nucleotide sequence designated as the primer
      binding site (PBS) which is complementary to the tRNA used for initiation of
      reverse transcription. For human immunodeficiency virus type 1 (HIV-1), all
      naturally occurring genomes have a PBS complementary to tRNA3Lys. However, within
      HIV-1 virions, there are approximately equal amounts of tRNA1Lys, tRNA2Lys, and
      tRNA3Lys. We have used an endogenous reverse transcription-PCR technique specific
      for the tRNA species within isolated HIV-1 virions to demonstrate that in
      addition to tRNA3Lys, tRNA1Lys and tRNA2Lys could be used for initiation of HIV-1
      reverse transcription. Using a single-round infection assay which employed an HIV
      1 genome with a gpt gene encoding xanthine-guanine phosphoribosyl transferase in
      place of the env gene, we generated cell lines resistant to mycophenolic acid.
      Analysis of the U5-PBS from single-cell clones revealed PBS complementary to
      tRNA3Lys, not tRNA1Lys or tRNA2Lys. A mutant HIV-1 genome was then created which
      would favor the completion of reverse transcription with tRNA1,2Lys. Using this
      provirus in the complementation system, we again found only genomes with a PBS
      complementary to tRNA3Lys from proviral DNA isolated from gpt-resistant single
      cell colonies. Finally, infection of cells with a mutant HIV genome with a PBS
      complementary to tRNA1,2Lys resulted in gpt- resistant cell colonies which
      contained integrated provirions with a PBS complementary to tRNA1,2Lys. The
      results of these studies suggest that the selection of tRNA3Lys for initiation of
      HIV-1 reverse transcription occurs both at the initiation and at a postinitiation
      step in reverse transcription prior to integration of the proviral DNA.

PMID- 9621003
TI  - Characterization of wild-type adeno-associated virus type 2-like particles
      generated during recombinant viral vector production and strategies for their
      elimination.
AB  - The pSub201-pAAV/Ad plasmid cotransfection system was developed to eliminate
      homologous recombination which leads to generation of the wild-type (wt) adeno
      associated virus type 2 (AAV) during recombinant vector production. The extent of
      contamination with wt AAV has been documented to range between 0.01 and 10%.
      However, the precise mechanism of generation of the contaminating wt AAV remains
      unclear. To characterize the wt AAV genomes, recombinant viral stocks were used
      to infect human 293 cells in the presence of adenovirus. Southern blot analyses
      of viral replicative DNA intermediates revealed that the contaminating AAV
      genomes were not authentic wt but rather wt AAV-like sequences derived from
      recombination between (i) AAV inverted terminal repeats (ITRs) in the recombinant
      plasmid and (ii) AAV sequences in the helper plasmid. Replicative AAV DNA
      fragments, isolated following amplification through four successive rounds of
      amplification in adenovirus-infected 293 cells, were molecularly cloned and
      subjected to nucleotide sequencing to identify the recombinant junctions.
      Following sequence analyses of 31 different ends of AAV-like genomes derived from
      two different recombinant vector stocks, we observed that all recombination
      events involved 10 nucleotides in the AAV D sequence distal to viral hairpin
      structures. We have recently documented that the first 10 nucleotides in the D
      sequence proximal to the AAV hairpin structures are essential for successful
      replication and encapsidation of the viral genome (X.-S. Wang et al., J. Virol.
      71:3077-3082, 1997), and it was noteworthy that in each recombinant junction
      sequenced, the same 10 nucleotides were retained. We also observed that
      adenovirus ITRs in the helper plasmid were involved in illegitimate recombination
      with AAV ITRs, deletions of which significantly reduced the extent of wt AAV-like
      particles. Furthermore, the combined use of recombinant AAV plasmids lacking the
      distal 10 nucleotides in the D sequence and helper plasmids lacking the
      adenovirus ITRs led to complete elimination of replication-competent wt AAV-like
      particles in recombinant vector stocks. These strategies should be useful in
      producing clinical-grade AAV vectors suitable for human gene therapy.

PMID- 9621004
TI  - Phosphorylation of the human cytomegalovirus 86-kilodalton immediate-early
      protein IE2.
AB  - We have investigated the phosphorylation state of the human cytomegalovirus 86
      kDa immediate-early (IE) protein IEP86 from transfected and infected cells. We
      show that multiple domains of IEP86 are phosphorylated by cellular kinases, both
      in vitro and in vivo. Our data suggest that serum-inducible kinases play a
      significant role in cell-mediated IE protein phosphorylation and that a member of
      the mitogen-activated protein (MAP) kinase (MAPK) family, extracellular regulated
      kinase 2 (ERK2), phosphorylates several domains of IEP86 in vitro. Alanine
      substitution mutagenesis was performed on specific serines or threonines (T27,
      S144, T233/S234, and T555) found in consensus MAP kinase motifs. Analysis of
      these mutations showed that T27 and T233/S234 are the major sites for serum
      inducible kinases and are the major ERK2 sites in vitro. S144 appeared to be
      phosphorylated in a serum-independent manner in vitro. All of the mutations
      except T555 eliminated specific phosphorylation in vivo. In transient
      transfection analyses, IEP86 isoforms containing mutations in S144 and,
      especially, T233/S234 displayed increased transcriptional activation relative to
      the wild type, suggesting that phosphorylation at these sites in wild-type IEP86
      may result in reduction of its transcriptional activation ability.

PMID- 9621005
TI  - Influenza virus nucleoprotein interacts with influenza virus polymerase proteins.
AB  - Influenza virus nucleoprotein (NP) is a critical factor in the viral infectious
      cycle in switching influenza virus RNA synthesis from transcription mode to
      replication mode. In this study, we investigated the interaction of NP with the
      viral polymerase protein complex. Using coimmunoprecipitation with monospecific
      or monoclonal antibodies, we observed that NP interacted with the RNP-free
      polymerase protein complex in influenza virus-infected cells. In addition,
      coexpression of the components of the polymerase protein complex (PB1, PB2, or
      PA) with NP either together or pairwise revealed that NP interacts with PB1 and
      PB2 but not PA. Interaction of NP with PB1 and PB2 was confirmed by both
      coimmunoprecipitation and histidine tagging of the NP-PB1 and NP-PB2 complexes.
      Further, it was observed that NP-PB2 interaction was rather labile and sensitive
      to dissociation in 0.1% sodium dodecyl sulfate and that the stability of NP-PB2
      interaction was regulated by the sequences present at the COOH terminus of NP.
      Analysis of NP deletion mutants revealed that at least three regions of NP
      interacted independently with PB2. A detailed analysis of the COOH terminus of NP
      by mutation of serine-to-alanine (SA) residues either individually or together
      demonstrated that SA mutations in this region did not affect the binding of NP to
      PB2. However, some SA mutations at the COOH terminus drastically affected the
      functional activity of NP in an in vivo transcription-replication assay, whereas
      others exhibited a temperature-sensitive phenotype and still others had no effect
      on the transcription and replication of the viral RNA. These results suggest that
      a direct interaction of NP with polymerase proteins may be involved in regulating
      the switch of viral RNA synthesis from transcription to replication.

PMID- 9621006
TI  - Derivation and functional characterization of a consensus DNA binding sequence
      for the tas transcriptional activator of simian foamy virus type 1.
AB  - Although DNA binding sites specific for the Bel-1 and Tas transcriptional
      activators, encoded, respectively, by the human and simian foamy viruses, have
      been mutationally defined, they show little evident sequence identity. As a
      result, the sequence determinants for DNA binding by both Bel-1 and Tas have
      remained unclear. Here, we report the use of a novel in vivo randomization and
      selection strategy to identify a Tas DNA binding site consensus. This approach
      takes advantage of the fact that Tas can effectively activate gene expression in
      yeast cells via a Tas DNA binding site derived from the simian foamy virus type 1
      (SFV-1) internal promoter. The defined Tas DNA binding site consensus extends
      over approximately 25 bp and contains a critical core sequence of approximately 5
      bp. Positions adjacent to this core sequence, while clearly also subject to
      selection, show a significantly higher level of sequence variation. Surprisingly,
      the wild-type SFV-1 internal promoter Tas DNA binding site fails to conform to
      the consensus at several positions. Further analysis demonstrated that the
      consensus sequence bound Tas more effectively than did the wild-type sequence in
      vitro and could mediate an enhanced Tas response in vivo when substituted into
      the SFV-1 internal promoter context. These findings explain the limited sequence
      identity observed for mutationally defined Tas or Bel-1 response elements and
      should facilitate the identification of Tas DNA target sites located elsewhere in
      the SFV-1 genome.

PMID- 9621007
TI  - Sequences in pol are required for transfer of human foamy virus-based vectors.
AB  - A series of vectors with heterologous genes was constructed from HSRV1, an
      infectious clone of human foamy virus (HFV), and transfected into baby hamster
      kidney cells to generate stably transfected vector cell lines. Two cis-acting
      sequences were required to achieve efficient rescue by helper virus. The first
      element was located at the 5' end upstream of position 1274 of the proviral DNA.
      Interestingly, a mutation in the leader sequence which decreased the ability to
      dimerize in vitro inhibited transfer by helper HFV. A second element that was
      important for vector transfer was located in the pol gene between positions 5638
      and 6317. Constructs lacking this element were only poorly transferred by helper
      HFV, even though their RNA was produced in the vector cell lines. This finding
      rules out the possibility that the observed lack of transfer was due to RNA
      instability. A minimal vector containing only these two elements could be
      successfully delivered by helper HFV, confirming that all essential cis-acting
      sequences were present. The presence of a sequence described as a second
      polypurine tract in HFV was not necessary for transfer. Our data identified the
      minimal sequence requirements for HFV vector transfer for the development of
      useful vector systems.

PMID- 9621008
TI  - Differential selection of cells with proviral c-myc and c-erbB integrations after
      avian leukosis virus infection.
AB  - Avian leukosis virus (ALV) infection induces bursal lymphomas in chickens after
      proviral integration within the c-myc proto-oncogene and induces erythroblastosis
      after integration within the c-erbB proto-oncogene. A nested PCR assay was used
      to analyze the appearance of these integrations at an early stage of tumor
      induction after infection of embryos. Five to eight distinct proviral c-myc
      integration events were amplified from bursas of infected 35-day-old birds, in
      good agreement with the number of transformed bursal follicles arising with these
      integrations. Cells containing these integrations are remarkably common, with an
      estimated 1 in 350 bursal cells having proviral c-myc integrations. These
      integrations were clustered within the 3' half of c-myc intron 1, in a pattern
      similar to that observed in bursal lymphomas. Bone marrow and spleen showed a
      similar number and pattern of integrations clustered within 3' c-myc intron 1,
      indicating that this region is a common integration target whether or not that
      tissue undergoes tumor induction. While all tissues showed equivalent levels of
      viral infection, cells with c-myc integrations were much more abundant in the
      bursa than in other tissues, indicating that cells with proviral c-myc
      integrations are preferentially expanded within the bursal environment. Proviral
      integration within the c-erbB gene was also analyzed, to detect clustered c-erbB
      intron 14 integrations associated with erythroblastosis. Proviral c-erbB
      integrations were equally abundant in the bone marrow, spleen, and bursa. These
      integrations were randomly situated upstream of c-erbB exon 15, indicating that
      cells carrying 3' intron 14 integrations must be selected during induction of
      erythroblastosis.

PMID- 9621009
TI  - An interferon regulatory factor binding site in the U5 region of the bovine
      leukemia virus long terminal repeat stimulates Tax-independent gene expression.
AB  - Bovine leukemia virus (BLV) replication is controlled by both cis- and trans
      acting elements. The virus-encoded transactivator, Tax, is necessary for
      efficient transcription from the BLV promoter, although it is not present during
      the early stages of infection. Therefore, sequences that control Tax-independent
      transcription must play an important role in the initiation of viral gene
      expression. This study demonstrates that the R-U5 sequence of BLV stimulates Tax
      independent reporter gene expression directed by the BLV promoter. R-U5 was also
      stimulatory when inserted immediately downstream from the transcription
      initiation site of a heterologous promoter. Progressive deletion analysis of this
      region revealed that a 46-bp element corresponding to the 5' half of U5 is
      principally responsible for the stimulation. This element exhibited enhancer
      activity when inserted upstream or downstream from the herpes simplex virus
      thymidine kinase promoter. This enhancer contains a binding site for the
      interferon regulatory factors IRF-1 and IRF-2. A 3-bp mutation that destroys the
      IRF recognition site caused a twofold decrease in Tax-independent BLV long
      terminal repeat-driven gene expression. These observations suggest that the IRF
      binding site in the U5 region of BLV plays a role in the initiation of virus
      replication.

PMID- 9621010
TI  - Intracellular signaling by the chemokine receptor US28 during human
      cytomegalovirus infection.
AB  - In patients with impaired cell-mediated immune responses (e.g., lung transplant
      recipients and AIDS patients), cytomegalovirus (CMV) infection causes severe
      disease such as pneumonitis. However, although immunocompetency in the host can
      protect from CMV disease, the virus persists by evading the host immune defenses.
      A model of CMV infection of the endothelium has been developed in which
      inflammatory stimuli, such as the CC chemokine RANTES, bind to the endothelial
      cell surface, stimulating calcium flux during late times of CMV infection. At 96
      h postinfection, CMV-infected cells express mRNA of the CMV-encoded CC chemokine
      receptor US28 but do not express mRNA of other CC chemokine receptors that bind
      RANTES (CCR1, CCR4, CCR5). Cloning and stable expression of the receptor CMV US28
      in human kidney epithelial cells (293 cells) with and without the heterotrimeric
      G protein alpha16 indicated that CMV US28 couples to both Galphai and Galpha16
      proteins to activate calcium flux in response to the chemokines RANTES and MCP-3.
      Furthermore, cells that coexpress US28 and Galpha16 responded to RANTES
      stimulation with activation of extracellular signal-regulated kinase, which could
      be attributed, in part, to specific Galpha16 coupling. Thus, through expression
      of the CC chemokine receptor US28, CMV may utilize resident G proteins of the
      infected cell to manipulate cellular responses stimulated by chemokines.

PMID- 9621011
TI  - Modulation of viral immunoinflammatory responses with cytokine DNA administered
      by different routes.
AB  - The efficacy of plasmid DNA encoding cytokine administered by different routes,
      systemic or surface exposure, was evaluated and compared for their modulating
      effects on subsequent lesions caused by infection with herpes simplex virus
      (HSV). Systemic or topical administration of both interleukin-4 (IL-4) and IL-10
      DNA but not IL-2 DNA caused a long-lasting suppression of HSV-specific delayed
      type hypersensitivity response. IL-4 or IL-10 DNA preadministration also
      modulated the expression of immunoinflammatory lesions associated with corneal
      infection of HSV. Suppression of ocular lesions required that the DNA be
      administered to the nasal mucosa or ocular surfaces and was not evident after
      intramuscular administration. The modulating effect of IL-10 DNA was most evident
      after topical ocular administration, whereas the effects of IL-4 DNA given by
      both routes appeared to be equal. Preexposure of IL-4 DNA, but not IL-10 DNA,
      resulted in a significant change in Th subset balance following HSV infection.
      Our results indicate that the modulating effect of IL-4 or IL-10 DNA may proceed
      by different mechanisms. Furthermore, our results suggest that surface
      administration of cytokine DNA is a convenient means of modulating
      immunoinflammatory lesions.

PMID- 9621012
TI  - Epstein-Barr virus uses different complexes of glycoproteins gH and gL to infect
      B lymphocytes and epithelial cells.
AB  - The Epstein-Barr virus (EBV) gH-gL complex includes a third glycoprotein, gp42.
      gp42 binds to HLA class II on the surfaces of B lymphocytes, and this interaction
      is essential for infection of the B cell. We report here that, in contrast, gp42
      is dispensable for infection of epithelial cell line SVKCR2. A soluble form of
      gp42, gp42.Fc, can, however, inhibit infection of both cell types. Soluble gp42
      can interact with EBV gH and gL and can rescue the ability of virus lacking gp42
      to transform B cells, suggesting that a gH-gL-gp42.Fc complex can be formed by
      extrinsic addition of the soluble protein. Truncated forms of gp42.Fc that retain
      the ability to bind HLA class II but that cannot interact with gH and gL still
      inhibit B-cell infection by wild-type virus but cannot inhibit infection of
      SVKCR2 cells or rescue the ability of recombinant gp42-negative virus to
      transform B cells. An analysis of wild-type virions indicates the presence of
      more gH and gL than gp42. To explain these results, we describe a model in which
      wild-type EBV virions are proposed to contain two types of gH-gL complexes, one
      that includes gp42 and one that does not. We further propose that these two forms
      of the complex have mutually exclusive abilities to mediate the infection of B
      cells and epithelial cells. Conversion of one to the other concurrently alters
      the ability of virus to infect each cell type. The model also suggests that
      epithelial cells may express a molecule that serves the same cofactor function
      for this cell type as HLA class II does for B cells and that the gH-gL complex
      interacts directly with this putative epithelial cofactor.

PMID- 9621013
TI  - The Epstein-Barr virus (EBV) gN homolog BLRF1 encodes a 15-kilodalton
      glycoprotein that cannot be authentically processed unless it is coexpressed with
      the EBV gM homolog BBRF3.
AB  - The Epstein-Barr virus (EBV) homolog of the conserved herpesvirus glycoprotein gN
      is predicted to be encoded by the BLRF1 open reading frame (ORF). Antipeptide
      antibody to a sequence corresponding to residues in the predicted BLRF1 ORF
      immunoprecipitated a doublet of approximately 8 kDa from cells expressing the
      BLRF1 ORF as a recombinant protein. In addition, four glycosylated proteins of
      113, 84, 48, and 15 kDa could be immunoprecipitated from virus-producing cells by
      the same antibody. The 15-kDa species was the mature form of gN, which carried
      alpha2,6-sialic acid residues. The remaining glycoproteins which associated with
      gN were products of the BBRF3 ORF of EBV, which encodes the EBV gM homolog. The 8
      kDa doublet seen in cells expressing recombinant gN comprised precursors of the
      mature 15-kDa gN. Coexpression of EBV gM with EBV gN was required for authentic
      processing of the 8-kDa forms to the 15-kDa form.

PMID- 9621014
TI  - The length and sequence composition of vesicular stomatitis virus intergenic
      regions affect mRNA levels and the site of transcript initiation.
AB  - In this study, we used a dicistronic vesicular stomatitis virus (VSV) minigenome
      to investigate the effects of either single or multiple nucleotide insertions
      placed immediately after the nontranscribed intergenic dinucleotide of the M gene
      on VSV transcription. Both Northern blot and primer extension analysis showed
      that the polymerase responded to the inserted nucleotides in a sequence-specific
      manner such that some insertions had no effect on mRNA synthesis from the
      downstream G gene, nor on the site of transcript initiation, whereas other
      insertions resulted in dramatic reductions in transcript accumulation. Some of
      these transcripts were initiated at the wild-type site, while others initiated
      within the inserted sequence. We also examined the transcriptional events that
      occurred when a natural, 21-nucleotide intergenic region located between the G
      and L genes from the New Jersey (NJ) serotype of VSV was inserted into the
      minigenome gene junction. In contrast to the normal 25 to 30% attenuation
      observed for downstream transcription at gene junctions containing the typical
      dinucleotide (3'-GA-5') intergenic region, the NJ variant showed greater than 75%
      attenuation at the gene junction. In addition, the polymerase initiated
      transcription at two major start sites, one of which was located within the
      intergenic sequence. Collectively, these data suggest that the polymerase
      "samples" the intergenic sequences following polyadenylation and termination of
      the upstream transcript by scanning until an appropriate start site is found. One
      implication of a scanning polymerase is that the polymerase presumably switches
      states from a processive elongation mode to a stuttering mode for polyadenylation
      to one in which no transcription occurs, before it reinitiates at the downstream
      gene. Our data support the hypothesis that sequences surrounding the intergenic
      region modulate these events such that appropriate amounts of each mRNA are
      synthesized.

PMID- 9621015
TI  - Role of the pre-S2 domain of the large envelope protein in hepatitis B virus
      assembly and infectivity.
AB  - Among the three viral proteins present in the hepatitis B virus (HBV) envelope,
      both the small and large polypeptides, but not the middle polypeptide, are
      necessary for the production of complete viral particles. Whereas it has been
      established that the C-terminal extremity of the pre-S1 region is required for
      HBV morphogenesis, whether the pre-S2 region of the large surface protein plays a
      critical role remains questionable. In the present study, we have analyzed the
      role of the large-polypeptide pre-S2 region in viral maturation and infectivity.
      For this purpose, mutants bearing contiguous deletions covering the entire pre-S2
      domain were generated. First, the efficient expression of all the mutant large
      envelope proteins was verified and their ability to substitute for the wild-type
      form in virion secretion was tested. We found that distinct deletions covering
      the domain between amino acids 114 and 163 still allowed virion production. In
      contrast, the polypeptide lacking the first 5 amino acids of pre-S2 (amino acids
      109 to 113) was unable to support viral secretion. This result shows that the
      domain of the large surface protein, required for this process, must be extended
      to the N-terminal extremity of pre-S2. We then demonstrated that all the mutants
      competent for virion release were able to infect normal human hepatocytes in
      primary culture. Taken together, these results indicate that only 10% of the
      large-protein pre-S2 region at its N-terminal extremity is essential for virion
      export and that the remaining part, dispensable for viral secretion, is also
      dispensable for infectivity.

PMID- 9621016
TI  - Members of the GATA family of transcription factors bind to the U3 region of Cas
      Br-E and graffi retroviruses and transactivate their expression.
AB  - Cas-Br-E and Graffi are two murine viruses that induce myeloid leukemia in mice:
      while Cas-Br-E induces mostly non-T, non-B leukemia composed of very immature
      cells, Graffi causes exclusively a granulocytic leukemia (E. Rassart, J. Houde,
      C. Denicourt, M. Ru, C. Barat, E. Edouard, L. Poliquin, and D. Bergeron, Curr.
      Top. Microbiol. Immunol. 211:201-210, 1995). In an attempt to understand the
      basis of the myeloid specificity of these two retroviruses, we used DNase I
      footprinting analysis and gel mobility shift assays to identify a number of
      protein binding sites within the Cas-Br-E and Graffi U3 regions. Two protected
      regions include potential GATA binding sites. Methylation interference analysis
      with different hematopoietic nuclear extracts showed the importance of the G
      residues in these GATA sites, and supershift assays clearly identified the
      binding factors as GATA-1, GATA-2, and GATA-3. Transient assays with long
      terminal repeat (LTR)-chloramphenicol acetyltransferase constructs showed that
      these three GATA family members are indeed able to transactivate Cas-Br-E and
      Graffi LTRs. Thus, the availability and relative abundance of the various members
      of the GATA family of transcription factors in a given cell type could influence
      the transcriptional tissue specificity of murine leukemia viruses and hence their
      disease specificity.

PMID- 9621017
TI  - Sequences just upstream of the simian immunodeficiency virus core enhancer allow
      efficient replication in the absence of NF-kappaB and Sp1 binding elements.
AB  - Large deletions of the upstream U3 sequences in the long terminal repeats (LTRs)
      of human immunodeficiency virus and simian immunodeficiency virus (SIV)
      accumulate in vivo in the absence of an intact nef gene. In the SIV U3 region,
      about 65 bp just upstream of the single NF-kappaB binding site always remained
      intact, and some evidence for a novel enhancer element in this region exists. We
      analyzed the transcriptional and replicative capacities of SIVmac239 mutants
      containing deletions or mutations in these upstream U3 sequences and/or the NF
      kappaB and Sp1 binding sites. Even in the absence of 400 bp of upstream U3
      sequences, the NF-kappaB site and all four Sp1 binding sites, the SIV promoter
      maintained about 15% of the wild-type LTR activity and was fully responsive to
      Tat activation in transient reporter assays. The effects of these deletions on
      virus production after transfection of COS-1 cells with full-length proviral
      constructs were much greater. Deletion of the upstream U3 sequences had no
      significant influence on viral replication when either the single NF-kappaB site
      or the Sp1 binding sites were intact. In contrast, the 26 bp of sequence located
      immediately upstream of the NF-kappaB site was essential for efficient
      replication when all core enhancer elements were deleted. A purine-rich site in
      this region binds specifically to the transcription factor Elf-1, a member of the
      ets proto-oncogene-encoded family. Our results indicate a high degree of
      functional redundancy in the SIVmac U3 region. Furthermore, we defined a novel
      regulatory element located immediately upstream of the NF-kappaB binding site
      that allows efficient viral replication in the absence of the entire core
      enhancer region.

PMID- 9621018
TI  - The effects of pharmacological and lentivirus-induced immune suppression on
      orbivirus pathogenesis: assessment of virus burden in blood monocytes and tissues
      by reverse transcription-in situ PCR.
AB  - We investigated the effects of pharmacological and lentivirus-induced
      immunosuppression on bluetongue virus (BTV) pathogenesis as a mechanism for virus
      persistence and induction of clinical disease. Immunologically normal and
      immunosuppressed sheep were infected subcutaneously with BTV serotype 3 (BTV-3),
      a foreign isolate with unknown pathogenicity in North American livestock, and
      with North American serotype 11 (BTV-11). Erythrocyte-associated BTV RNA was
      detected earlier and at greater concentrations in sheep treated with
      immunosuppressive drugs. Similarly, viral RNA and infectious virus were detected
      in blood monocytes earlier and at higher frequency in immunosuppressed animals:
      as many as 1 in 970 monocytes revealed BTV RNA at peak viremia, compared to <1 in
      10(5) monocytes from immunocompetent sheep. Animals infected with BTV-3 had a
      higher virus burden in monocytes and lesions of greater severity than those
      infected with BTV-11. BTV RNA was detected by in situ hybridization in vascular
      endothelial cells and cells of monocyte lineage, but only in tissues from
      immunocompromised animals, and was most abundant in animals infected with BTV-3.
      In contrast, reverse transcription-in situ PCR showed BTV RNA from both viral
      serotypes in high numbers of tissue leukocytes and vascular endothelial cells
      from both immunosuppressed and, to a lesser extent, immunocompetent animals.
      Collectively, these findings show that BTV infection is widely distributed during
      acute infection but replication is highly restricted in animals with normal
      immunity. These findings also suggest that in addition to virulence factors that
      define viral serotypes, immunosuppression could play a role in the natural
      history of orbivirus infection, allowing for higher virus burden, increased virus
      persistence, and greater potential for acquisition of virus by the arthropod
      vector.

PMID- 9621019
TI  - Persistent activation of RelA by respiratory syncytial virus involves protein
      kinase C, underphosphorylated IkappaBbeta, and sequestration of protein
      phosphatase 2A by the viral phosphoprotein.
AB  - Respiratory syncytial virus (RSV) activated the RelA (p65) subunit of nuclear
      factor kappa B (NF-kappaB) over many hours postinfection. The initial activation
      coincided with phosphorylation and degradation of IkappaBalpha, the cytoplasmic
      inhibitor of RelA. During persistent activation of NF-kappaB at later times in
      infection, syntheses of inhibitors IkappaBalpha as well as IkappaBbeta were
      restored. However, the resynthesized IkappaBbeta was in an underphosphorylated
      state, which apparently prevented inhibition of NF-kappaB. Use of specific
      inhibitors suggested that the pathway leading to the persistent-but not the
      initial-activation of NF-kappaB involved signaling through protein kinase C (PKC)
      and reactive oxygen intermediates of nonmitochondrial origin, whereas
      phospholipase C or D played little or no role. Thus, RSV infection led to the
      activation of NF-kappaB by a biphasic mechanism: a transient or early activation
      involving phosphorylation of the inhibitor IkappaB polypeptides, and a persistent
      or long-term activation requiring PKC and the generation of hypophosphorylated
      IkappaBbeta. At least a part of the activation was through a novel mechanism in
      which the viral phosphoprotein P associated with but was not dephosphorylated by
      protein phosphatase 2A and thus sequestered and inhibited the latter. We
      postulate that this led to a net increase in the phosphorylation state of
      signaling proteins that are responsible for RelA activation.

PMID- 9621020
TI  - The neuroinvasiveness of a murine retrovirus is influenced by a dileucine
      containing sequence in the cytoplasmic tail of glycosylated Gag.
AB  - The tempo and intensity of retroviral neuropathogenesis are dependent on the
      capacity of the virus to invade the central nervous system. For murine leukemia
      viruses, an important determinant of neuroinvasiveness is the virus-encoded
      protein glycosylated Gag, the function of which in the virus life cycle is not
      known. While this protein is dispensable for virus replication, mutations which
      prevent its expression slow the spread of virus in vivo and restrict virus
      dissemination to the brain. To further explore the function of this protein, we
      compared two viruses, CasFrKP (KP) and CasFrKP41 (KP41), which differ
      dramatically in neurovirulence. KP expresses high early viremia titers, is
      neuroinvasive, and induces clinical neurologic disease in 100% of neonatally
      inoculated mice, with an incubation period of 18 to 23 days. In contrast, KP41
      expresses early viremia titers 100- fold lower than those of KP, exhibits
      attenuated neuroinvasiveness, and induces clinical neurologic disease
      infrequently, with a relatively long incubation period. The genomes of these two
      viruses differ by only 10 nucleotides, resulting in differences at five residues,
      all located within the N-terminal cytoplasmic tail of glycosylated Gag. In this
      study, using KP as the parental virus, we systematically mutated each of the five
      amino acid residues to those of KP41 and found that substitution mutation of two
      membrane-proximal residues, E53 and L56, to K and P, respectively produced the
      greatest effect on early viremia kinetics and neurovirulence. These mutations
      disrupted the KP sequence E53FLL56, the leucine dipeptide of which suggests the
      possibility that it may represent a sorting signal for glycosylated Gag.
      Supporting this idea was the finding that alteration of this sequence motif
      increased the level of cell surface expression of the protein, which suggests
      that analysis of the intracellular trafficking of glycosylated Gag may provide
      further clues to its function.

PMID- 9621021
TI  - Requirement for cellular cyclin-dependent kinases in herpes simplex virus
      replication and transcription.
AB  - Several observations indicate that late-G1/S-phase-specific cellular functions
      may be required for herpes simplex virus (HSV) replication: (i) certain mutant
      HSV strains are replication impaired during infection of cells in the G0/G1 but
      not in the G1/S phase of the cell cycle, (ii) several late-G1/S-phase-specific
      cellular proteins and functions are induced during infection, and (iii) the
      activity of a cellular protein essential for expression of viral immediate-early
      (IE) genes, HCF, is normally required during the late G1/S phase of the cell
      cycle. To test the hypothesis that late-G1/S-phase-specific cellular functions
      are necessary for HSV replication, HEL or Vero cells were infected in the
      presence of the cell cycle inhibitors roscovitine (Rosco) and olomoucine (Olo).
      Both drugs inhibit cyclin-dependent kinase 1 (cdk-1) and cdk-2 (required for cell
      cycle progression into the late G1/S phase) and cdk-5 (inactive in cycling cells)
      but not cdk-4 or cdk-6 (active at early G1). We found that HSV replication was
      inhibited by Rosco and Olo but not by lovastatin (a cell cycle inhibitor that
      does not inhibit cdk activity), staurosporine (a broad-spectrum protein serine
      threonine kinase inhibitor), PD98059 (an inhibitor specific for erk-1 and -2) or
      iso-Olo (a structural isomer of Olo that does not inhibit cdk activity). The
      concentrations of Rosco and Olo required to inhibit cell cycle progression and
      viral replication in both HEL and Vero cells were similar. Inhibition of viral
      replication was found not to be mediated by drug-induced cytotoxicity. Efforts to
      isolate Rosco- or Olo-resistant HSV mutants were unsuccessful, indicating that
      these drugs do not act by inhibiting a single viral target. Viral DNA replication
      and accumulation of IE and early viral RNAs were inhibited in the presence of
      cell cycle-inhibitory concentrations of Rosco or Olo. We therefore conclude that
      one or more cdks active from late G1 onward or inactive in nonneuronal cells are
      required for accumulation of HSV transcripts, viral DNA replication, and
      production of infectious virus.

PMID- 9621022
TI  - A small yeast RNA blocks hepatitis C virus internal ribosome entry site (HCV
      IRES)-mediated translation and inhibits replication of a chimeric poliovirus
      under translational control of the HCV IRES element.
AB  - Hepatitis C virus (HCV) infection frequently leads to chronic hepatitis and
      cirrhosis of the liver and has been linked to development of hepatocellular
      carcinoma. We previously identified a small yeast RNA (IRNA) capable of
      specifically inhibiting poliovirus (PV) internal ribosome entry site (IRES)
      mediated translation. Here we report that IRNA specifically inhibits HCV IRES
      mediated translation both in vivo and in vitro. A number of human hepatoma (Huh
      7) cell lines expressing IRNA were prepared and characterized. Constitutive
      expression of IRNA was not detrimental to cell growth. HCV IRES-mediated cap
      independent translation was markedly inhibited in cells constitutively expressing
      IRNA compared to control hepatoma cells. However, cap-dependent translation was
      not significantly affected in these cell lines. Additionally, Huh-7 cells
      constitutively expressing IRNA became refractory to infection by a PV-HCV chimera
      in which the PV IRES is replaced by the HCV IRES. In contrast, replication of a
      PV-encephalomyocarditis virus (EMCV) chimera containing the EMCV IRES element was
      not affected significantly in the IRNA-producing cell line. Finally, the binding
      of the La autoantigen to the HCV IRES element was specifically and efficiently
      competed by IRNA. These results provide a basis for development of novel drugs
      effective against HCV infection.

PMID- 9621023
TI  - Protective CD4+ and CD8+ T cells against influenza virus induced by vaccination
      with nucleoprotein DNA.
AB  - DNA vaccination is an effective means of eliciting both humoral and cellular
      immunity, including cytotoxic T lymphocytes (CTL). Using an influenza virus
      model, we previously demonstrated that injection of DNA encoding influenza virus
      nucleoprotein (NP) induced major histocompatibility complex class I-restricted
      CTL and cross-strain protection from lethal virus challenge in mice (J. B. Ulmer
      et al., Science 259:1745-1749, 1993). In the present study, we have characterized
      in more detail the cellular immune responses induced by NP DNA, which included
      robust lymphoproliferation and Th1-type cytokine secretion (high levels of gamma
      interferon and interleukin-2 [IL-2], with little IL-4 or IL-10) in response to
      antigen-specific restimulation of splenocytes in vitro. These responses were
      mediated by CD4+ T cells, as shown by in vitro depletion of T-cell subsets. Taken
      together, these results indicate that immunization with NP DNA primes both
      cytolytic CD8+ T cells and cytokine-secreting CD4+ T cells. Further, we
      demonstrate by adoptive transfer and in vivo depletion of T-cell subsets that
      both of these types of T cells act as effectors in protective immunity against
      influenza virus challenge conferred by NP DNA.

PMID- 9621024
TI  - NF-kappaB-mediated inhibition of apoptosis is required for encephalomyocarditis
      virus virulence: a mechanism of resistance in p50 knockout mice.
AB  - Apoptosis is a central host defense mechanism to eliminate virus-infected cells.
      Activation of NF-kappaB suppresses apoptosis following some types of stimulation
      in vitro. To test the physiological importance of this pathway in vivo, we
      studied murine encephalomyocarditis virus (EMCV) infection in mice and cell lines
      defective in NF-kappaB1 (p50) signaling. As previously reported, we find that all
      p50 knockout (p50 -/-) mice survive an EMCV infection that readily kills normal
      mice. By introducing the p50 mutation into interferon (IFN) type I receptor
      knockout (IFNRI -/-) mice, we find that this resistance is not mediated by IFN
      beta as previously thought. While no IFNRI -/- mice survive, the double-knockout
      mice survive 60% of the time. The survival is tightly linked to the animals'
      ability to clear the virus from the heart in vivo. Using murine embryonic
      fibroblasts (MEF) derived from wild-type, p50 -/-, and p65 -/- embryos, we found
      that NF-kappaB is not required for the replication cycle of EMCV. However, during
      these experiments we observed that p50 -/- and p65 -/- MEF infected with EMCV
      undergo enhanced, premature cytotoxicity. Upon examination of this cell death, we
      found that EMCV infection induced both plasma membrane and nuclear changes
      typical of apoptosis in all cell lines. These apoptotic processes occurred in an
      accelerated and pronounced way in the NF-kappaB-defective cells, as soon as 6 h
      after infection, when virus is beginning to be released. Previously, only the
      RelA (p65) subunit of NF-kappaB has been shown to play a role in suppressing
      apoptosis. In our studies, we find that p50 is equally important in suppressing
      apoptosis during EMCV infection. Additionally, we show that suppression of
      apoptosis by NF-kappaB1 is required for EMCV virulence in vivo. The attenuation
      in p50 -/- mice can be explained by rapid apoptosis of infected cells which
      allows host phagocytes to clear infected cells before the viral burst leading to
      a reduction of the viral burden and survival of the mice.

PMID- 9621025
TI  - Human cytomegalovirus persistently infects aortic endothelial cells.
AB  - Endothelial cells (EC) have been implicated as constituting an important cell
      type in the pathogenesis of human cytomegalovirus (HCMV). Microvascular and
      macrovascular EC exhibit different biochemical and functional properties
      depending on the organ of origin. Phenotypic differences between microvascular
      and macrovascular EC may alter the ability of these cells to support HCMV
      replication. In this study, we compared the replication of HCMV in primary
      macrovascular aortic EC (AEC) with that in brain microvascular EC (BMVEC). An
      examination of IE72, pp65, and gB viral antigen expression in BMVEC and AEC by
      immunoflourescence revealed similar frequencies of infected cells. Intracellular
      production of virus was 3 log units greater in BMVEC than in AEC, while equal
      quantities of extracellular virus were produced in both cell types. HCMV
      infection of BMVEC resulted in rapid cellular lysis, while the virus was nonlytic
      and continuously released from HCMV-infected AEC for the life span of the
      culture. An examination of infected cells by electron microscopy revealed the
      formation of abundant nucleocapsids in both AEC and BMVEC. However, significant
      amounts of mature viral particles were only detected in the cytoplasm of BMVEC.
      These observations indicate that levels of HCMV replication in EC obtained from
      different organs are distinct and suggest that persistently infected AEC may
      serve as a reservoir of virus.

PMID- 9621026
TI  - Sonchus yellow net rhabdovirus nuclear viroplasms contain polymerase-associated
      proteins.
AB  - We have initiated a study of the cytopathology of nucleorhabdoviruses by
      analyzing the subcellular localization of sonchus yellow net virus (SYNV) genomic
      and antigenomic RNAs and the encoded polymerase proteins. In situ hybridizations
      demonstrated that the minus-strand genomic RNA sequences are restricted to the
      nuclei of infected cells, while the complementary plus-strand antigenomic RNA
      sequences are present in both the nuclei and the cytoplasm. Immunofluorescence
      and immunogold labeling experiments also revealed that the nucleocapsid (N)
      protein and phosphoprotein (M2) are primarily localized to discrete regions
      within the nuclei and in virus particles that accumulate in perinuclear spaces.
      The N protein antiserum specifically labeled the nuclear viroplasms, whereas the
      M2 antiserum was more generally distributed throughout the nuclei. Antibody
      detection also indicated that the polymerase (L) protein is present in small
      amounts in the viroplasm. When the N and M2 proteins were expressed individually
      from the heterologous potato virus X (PVX) vector, both proteins preferentially
      accumulated in the nuclei. In addition, viroplasm-like inclusions formed in the
      nuclei of cells infected with the PVX vector containing the N gene. Fusions of
      the carboxy terminus of beta-glucuronidase to N and M2 resulted in staining of
      the nuclei of infected cells following expression from the PVX vector. Deletion
      analyses suggested that multiple regions of the N protein contain signals that
      are important for nuclear localization.

PMID- 9621027
TI  - A comprehensive panel of near-full-length clones and reference sequences for non
      subtype B isolates of human immunodeficiency virus type 1.
AB  - Non-subtype B viruses cause the vast majority of new human immunodeficiency virus
      type 1 (HIV-1) infections worldwide and are thus the major focus of international
      vaccine efforts. Although their geographic dissemination is carefully monitored,
      their immunogenic and biological properties remain largely unknown, in part
      because well-characterized virological reference reagents are lacking. In
      particular, full-length clones and sequences are rare, since subtype
      classification is frequently based on small PCR-derived viral fragments. There
      are only five proviral clones available for viruses other than subtype B, and
      these represent only 3 of the 10 proposed (group M) sequence subtypes. This lack
      of reference sequences also confounds the identification and analysis of mosaic
      (recombinant) genomes, which appear to be arising with increasing frequency in
      areas where multiple sequence subtypes cocirculate. To generate a more
      representative panel of non-subtype B reference reagents, we have cloned (by long
      PCR or lambda phage techniques) and sequenced 10 near-full-length HIV-1 genomes
      (lacking less than 80 bp of long terminal repeat sequences) from primary isolates
      collected at major epicenters of the global AIDS pandemic. Detailed phylogenetic
      analyses identified six that represented nonrecombinant members of HIV-1 subtypes
      A (92UG037.1), C (92BR025. 8), D (84ZR085.1 and 94UG114.1), F (93BR020.1), and H
      (90CF056.1), the last two comprising the first full-length examples of these
      subtypes. Four others were found to be complex mosaics of subtypes A and C
      (92RW009.6), A and G (92NG083.2 and 92NG003.1), and B and F (93BR029.4), again
      emphasizing the impact of intersubtype recombination on global HIV-1
      diversification. Although a number of clones had frameshift mutations or
      translational stop codons in major open reading frames, all the genomes contained
      a complete set of genes and three had intact genomic organizations without
      inactivating mutations. Reconstruction of one of these (94UG114.1) yielded
      replication-competent virus that grew to high titers in normal donor peripheral
      blood mononuclear cell cultures. This panel of non-subtype B reference genomes
      should prove valuable for structure-function studies of genetically diverse viral
      gene products, the generation of subtype-specific immunological reagents, and the
      production of DNA- and protein-based subunit vaccines directed against a broader
      spectrum of viruses.

PMID- 9621028
TI  - The role of mouse adenovirus type 1 early region 1A in acute and persistent
      infections in mice.
AB  - Mouse adenovirus type 1 (MAV-1) early region 1A (E1A) viral mutants were used to
      determine the importance of this region in pathogenesis and establishment of a
      persistent infection in the natural host. Lethal dose analysis with adult male
      Swiss outbred mice revealed a significant reduction in virulence for all of the
      E1A mutants. During acute infections with 10(5) PFU of virus, an E1A null mutant,
      pmE109, was found in the same organs (brain, spleen, and spinal cord) and the
      same cell types (endothelial cells and mononuclear cells in lymphoid tissue) as
      wild-type virus. Another null mutant, pmE112, was detected in the same organs but
      in lower numbers. However, when mice were given a lower dose, 1 PFU, pmE109 and
      pmE112 reached none of the target organs analyzed by 14 days postinfection
      (p.i.). The absence of E1A did not hinder the ability of MAV-1 to establish a
      persistent infection. Viral nucleic acid was detected by PCR amplification or in
      situ hybridization in the kidneys, brains, spleens, and prefemoral lymph nodes of
      mice infected with wild-type or mutant virus up to 55 weeks p.i. The brain,
      spleen, and lymph node are recognized sites of acute viral infection but are
      previously unrecognized sites for MAV-1 persistence. Evidence for the potential
      reactivation of persistent MAV-1 infections is also presented.

PMID- 9621029
TI  - Identification of the respiratory syncytial virus proteins required for formation
      and passage of helper-dependent infectious particles.
AB  - We developed a system to identify the viral proteins required for the packaging
      and passage of human respiratory syncytial virus (RSV) by reconstructing these
      events with cDNA-encoded components. Plasmids encoding individual RSV proteins,
      each under the control of a T7 promoter, were cotransfected in various
      combinations together with a plasmid containing a minigenome into cells infected
      with a vaccinia virus recombinant expressing T7 RNA polymerase. Supernatants from
      these cells were passaged onto fresh cells which were then superinfected with
      RSV. Functional reconstitution of RSV-specific packaging and passage was detected
      by expression of the reporter gene carried on the minigenome. As expected, the
      four nucleocapsid proteins N, P, L, and M2-1 failed to direct packaging and
      passage of the minigenome. Passage was achieved by further addition of plasmids
      expressing three membrane-associated proteins, M, G, and F; inclusion of the
      fourth envelope- associated protein, SH, did not alter passage efficiency.
      Passage was reduced 10- to 20-fold by omission of G and was abrogated by omission
      of either M or F. Coexpression of the nonstructural NS1 or NS2 protein had little
      effect on packaging and passage except through indirect effects on RNA synthesis
      in the initial transfection. The M2-1 transcription elongation factor was not
      required for the generation of passage-competent particles. However, addition of
      increasing quantities of M2-1 to the transfection mediated a dose-dependent
      inhibition of passage which was alleviated by coexpression of the putative
      negative regulatory factor M2-2. Omission of the L plasmid reduced passage 10- to
      20-fold, most likely due to reduced availability of encapsidated minigenomes for
      packaging. However, the residual level of passage indicated that neither L
      protein nor the process of RSV-specific RNA synthesis is required for the
      production and passage of particles. Omission of N or P from the transfection
      abrogated passage. Thus, the minimum RSV protein requirements for packaging and
      passaging a minigenome are N, P, M, and F, although the efficiency is greatly
      increased by addition of L and G.

PMID- 9621030
TI  - A novel human cytomegalovirus glycoprotein, gpUS9, which promotes cell-to-cell
      spread in polarized epithelial cells, colocalizes with the cytoskeletal proteins
      E-cadherin and F-actin.
AB  - Processes by which human herpesviruses penetrate and are released from polarized
      epithelial cells, which have distinct apical and basolateral membrane domains
      differing in protein and lipid content, are poorly understood. We recently
      reported that human cytomegalovirus (CMV) mutants with deletions of the gene US9
      formed wild-type plaques in cultures of human fibroblasts but were impaired in
      the capacity for cell-to-cell spread in polarized human retinal pigment
      epithelial cells. Unlike the glycoproteins that are required for infection, the
      protein encoded by CMV US9 plays an accessory role by promoting dissemination of
      virus across cell-cell junctions of polarized epithelial cells. To identify the
      product and investigate its specialized functions, we selected Madine-Darby
      canine kidney II (MDCK) epithelial cells that constitutively express CMV US9 or,
      as a control, US8. The gene products, designated gpUS9 and gpUS8, were
      glycosylated proteins of comparable molecular masses but differed considerably in
      intracellular distribution and solubility. Immunofluorescence laser scanning
      confocal microscopy indicated that, like gpUS8, gpUS9 was present in the
      endoplasmic reticulum and Golgi compartments of nonpolarized cells. In polarized
      epithelial cells, gpUS9 also accumulated along lateral membranes, colocalizing
      with cadherin and actin, and was insoluble in Triton X-100, a property shared
      with proteins that associate with the cytoskeleton. We hypothesize that gpUS9 may
      enhance the dissemination of CMV in infected epithelial tissues by associating
      with the cytoskeletal matrix.

PMID- 9621031
TI  - Rabbit cells expressing human CD4 and human CCR5 are highly permissive for human
      immunodeficiency virus type 1 infection.
AB  - To evaluate the feasibility of using transgenic rabbits expressing CCR5 and CD4
      as a small-animal model of human immunodeficiency virus type 1 (HIV) disease, we
      examined whether the expression of the human chemokine receptor (CCR5) and human
      CD4 would render a rabbit cell line (SIRC) permissive to HIV replication.
      Histologically, SIRC cells expressing CD4 and CCR5 formed multinucleated cells
      (syncytia) upon exposure to BaL, a macrophagetropic strain of HIV that uses CCR5
      for cell entry. Intracellular viral capsid p24 staining showed abundant viral
      gene expression in BaL-infected SIRC cells expressing CD4 and CCR5. In contrast,
      neither SIRC cells expressing CD4 alone nor murine 3T3 cells expressing CCR5 and
      CD4 exhibited significant expression of p24. These stably transfected rabbit
      cells were also highly permissive for the production of virions upon infection by
      two other CCR5-dependent strains (JR-CSF and YU-2) but not by a CXCR4-dependent
      strain (NL4-3). The functional integrity of these virions was demonstrated by the
      successful infection of human peripheral blood mononuclear cells (PBMC) with
      viral stocks prepared from these transfected rabbit cells. Furthermore, primary
      rabbit PBMC were found to be permissive for production of infectious virions
      after circumventing the cellular entry step. These results suggest that a
      transgenic rabbit model for the study of HIV disease may be feasible.

PMID- 9621032
TI  - Distinct roles of two binding sites for the bovine papillomavirus (BPV) E2
      transactivator on BPV DNA replication.
AB  - The modulation of DNA replication by transcription factors was examined by using
      bovine papillomavirus type 1 (BPV). BPV replication in vivo requires two viral
      proteins: E1, an origin-binding protein, and E2, a transcriptional
      transactivator. In the origin, E1 interacts with a central region flanked by two
      binding sites for E2 (BS11 and BS12), of which only BS12 has been reported to be
      essential for replication in vivo. Using chemical interference and
      electrophoretic mobility shift assays, we found that the binding of E2 to each
      site stimulates the formation of distinct E1-origin complexes. A high-mobility C1
      complex is formed by using critical E2 contacts to BS12 and E1 contacts to the
      dyad symmetry element. In contrast, interaction of E2 with the BS11 element on
      the other origin flank promotes the formation of the lower-mobility C3 complex.
      C3 is a novel species that resembles C2, a previously identified complex that is
      replication active and formed by E1 alone. The binding of E1 greatly differs in
      the C1 and C3 complexes, with E1 in the C1 complex limited to the origin dyad
      symmetry region and E1 in the C3 complex encompassing the region from the
      proximal edge of BS11 through the distal edge of BS12. We found that the presence
      of both E2-binding sites is necessary for wild-type replication activity in vivo,
      as well as for maximal production of the C3 complex. These results show that in
      the normal viral context, BS11 and BS12 play separate but synergetic roles in the
      initiation of viral DNA replication that are dependent on their location within
      the origin. Our data suggest a model in which the binding of E2 to each site
      sequentially stimulates the formation of distinct E1-origin complexes, leading to
      the replication-competent complex.

PMID- 9621033
TI  - B-Cell lymphoma induction by akv murine leukemia viruses harboring one or both
      copies of the tandem repeat in the U3 enhancer.
AB  - Akv is an endogenous, ecotropic murine leukemia virus (MuLV) of the AKR strain.
      It has served as a prototype nonpathogenic or weakly pathogenic reference virus
      for studies of closely related potent lymphomagenic viruses such as the T
      lymphomagenic SL3-3. We here report that Akv and an Akv mutant (Akv1-99) with
      only one copy of the 99-bp transcriptional enhancer induce malignant lymphomas
      with nearly 100% incidence and mean latency periods of 12 months after injection
      into newborn NMRI mice. Molecular analysis of tumor DNA showed that the majority
      of the tumors were of the B-cell type. Sequence analysis of proviral
      transcriptional enhancers in DNA of B-cell lymphomas revealed conservation of the
      enhancer sequence, as well as a lack of sequence duplications of the Akv1-99
      variant, while the repeat copy number in Akv was subject to fluctuations. In
      support of a B-cell specificity of the Akv enhancer, a murine plasmacytoma cell
      line was found to sustain three- to fivefold-higher transient transcriptional
      activity upon the Akv and Akv1-99 enhancers than upon the enhancer of the T
      lymphomagenic SL3-3 MuLV. Thus, the overall picture is that Akv MuLV possesses a
      B- lymphomagenic potential and that the second copy of the 99-bp sequence seems
      to be of minor importance for this potential. However, in one animal the
      lymphomas induced by Akv1-99 were of the T-cell type. Among the 24 tumors
      analyzed only this one harbored a clonal proviral integration in the c-myc locus.
      This provirus had undergone a duplication of a 113-bp sequence of the enhancer
      region, partly overlapping with the 99-bp repeat of Akv, as well as a few single
      nucleotide alterations within and outside the repeats. Taken together with
      previous studies, our results suggest that T- versus B-lymphomagenic specificity
      of the enhancer is governed by more than one nucleotide difference and that
      alterations in binding sites for transcription factors of the AML1 and nuclear
      factor-1 families may contribute to this specificity.

PMID- 9621034
TI  - Protective immunity induced by oral immunization with a rotavirus DNA vaccine
      encapsulated in microparticles.
AB  - DNA vaccines are usually given by intramuscular injection or by gene gun delivery
      of DNA-coated particles into the epidermis. Induction of mucosal immunity by
      targeting DNA vaccines to mucosal surfaces may offer advantages, and an oral
      vaccine could be effective for controlling infections of the gut mucosa. In a
      murine model, we obtained protective immune responses after oral immunization
      with a rotavirus VP6 DNA vaccine encapsulated in poly(lactide-coglycolide) (PLG)
      microparticles. One dose of vaccine given to BALB/c mice elicited both rotavirus
      specific serum antibodies and intestinal immunoglobulin A (IgA). After challenge
      at 12 weeks postimmunization with homologous rotavirus, fecal rotavirus antigen
      was significantly reduced compared with controls. Earlier and higher fecal
      rotavirus-specific IgA responses were noted during the peak period of viral
      shedding, suggesting that protection was due to specific mucosal immune
      responses. The results that we obtained with PLG-encapsulated rotavirus VP6 DNA
      are the first to demonstrate protection against an infectious agent elicited
      after oral administration of a DNA vaccine.

PMID- 9621035
TI  - Determination of the nucleotide sequence of Bombyx mori cytoplasmic polyhedrosis
      virus segment 9 and its expression in BmN4 cells.
AB  - Cloning and sequencing of segment 9 of Bombyx mori cytoplasmic polyhedrosis virus
      (BmCPV) strains H and I were performed. The segment consisted of 1,186 bp
      harboring 5' and 3' noncoding regions and an open reading frame from positions 75
      to 1037, encoding a protein with 320 amino acids, termed NS5. Comparison of the
      nucleotide sequences of NS5 for the two strains indicated 37 point differences
      resulting in only six amino acid replacements. Homology search showed that NS5
      has localized similarities to human poliovirus RNA-dependent RNA polymerase and
      human rotavirus NS26. By Western blot analysis, NS5 was found in BmCPV-infected
      midgut cells, but not in polyhedra or virus virions, and was mainly detectable in
      the nucleus in BmCPV-infected BmN4 cells. Immunoblot analysis with anti-NS5 and
      antipolyhedrin antibodies displayed marked differences in the period of
      expression of NS5 and polyhedrin: the polyhedrin molecule was first detected 2 or
      3 days after infection with BmCPV, whereas the expression of NS5 was initiated
      within a few hours. In addition, the level of polyhedrin increased as the
      infection developed, whereas the amount of NS5 remained essentially constant.
      When segment 9 was expressed with a baculovirus expression system, the resulting
      NS5 protein possessed the ability to bind to the double-stranded RNA genome.
      These results suggest that NS5 is expressed in early stages of infection and
      contributes to regulation of genomic RNA function.

PMID- 9621036
TI  - DNA packaging mutant: repression of the vaccinia virus A32 gene results in
      noninfectious, DNA-deficient, spherical, enveloped particles.
AB  - The vaccinia virus A32 open reading frame was predicted to encode a protein with
      a nucleoside triphosphate-binding motif and a mass of 34 kDa. To investigate the
      role of this protein, we constructed a mutant in which the original A32 gene was
      replaced by an inducible copy. The recombinant virus, vA32i, has a conditional
      lethal phenotype: infectious virus formation was dependent on isopropyl-beta-D
      thiogalactopyranoside (IPTG). Under nonpermissive conditions, the mutant
      synthesized early- and late-stage viral proteins, as well as viral DNA that was
      processed into unit-length genomes. Electron microscopy of cells infected in the
      absence of IPTG revealed normal-appearing crescents and immature virus particles
      but very few with nucleoids. Instead of brick-shaped mature particles with
      defined core structures, there were numerous electron-dense, spherical particles.
      Some of these spherical particles were wrapped with cisternal membranes,
      analogous to intracellular and extracellular enveloped virions. Mutant viral
      particles, purified by sucrose density gradient centrifugation, had low
      infectivity and transcriptional activity, and the majority were spherical and
      lacked DNA. Nevertheless, the particle preparation contained representative
      membrane proteins, cleaved and uncleaved core proteins, the viral RNA polymerase,
      the early transcription factor and several enzymes, suggesting that incorporation
      of these components is not strictly coupled to DNA packaging.

PMID- 9621037
TI  - Human immunodeficiency virus type 1 vectors efficiently transduce human
      hematopoietic stem cells.
AB  - Lentiviruses are potentially advantageous compared to oncoretroviruses as gene
      transfer agents because they can infect nondividing cells. We demonstrate here
      that human immunodeficiency virus type 1 (HIV-1)-based vectors were highly
      efficient in transducing purified human hematopoietic stem cells. Transduction
      rates, measured by marker gene expression or by PCR of the integrated provirus,
      exceeded 50%, and transduction appeared to be independent of mitosis. Derivatives
      of HIV-1 were constructed to optimize the vector, and a deletion of most of Vif
      and Vpr was required to ensure the long-term persistence of transduced cells with
      relatively stable expression of the marker gene product. These results extend the
      utility of this lentivirus vector system.

PMID- 9621038
TI  - The duck hepatitis B virus polymerase is activated by its RNA packaging signal,
      epsilon.
AB  - The epsilon stem-loop at the 5' end of the pregenomic RNA of the hepatitis B
      viruses is both the primary element of the RNA packaging signal and the origin of
      reverse transcription. We have previously presented evidence for a third
      essential role for epsilon, that of an essential cofactor in the maturation of
      the viral polymerase (J. E. Tavis and D. Ganem, J. Virol. 70:5741-5750, 1996). In
      this case, binding of epsilon to the polymerase is proposed to induce a physical
      alteration to the polymerase that is needed for it to develop enzymatic activity.
      Three lines of evidence employing duck hepatitis B virus supporting this
      hypothesis are presented here. First, an unusual DNA polymerase activity
      employing exogenous RNAs (the trans reaction) that was originally discovered with
      recombinant duck hepatitis B virus polymerase expressed in Saccharomyces
      cerevisiae yeasts was shown to be an authentic property of the viral polymerase.
      The trans reaction was found to be template-dependent reverse transcription of
      the exogenous RNA. The trans reaction occurred independently of the hepadnavirus
      protein-priming mechanism, yet it was still strongly stimulated by epsilon. This
      directly demonstrates a role for epsilon in activation of the polymerase. Second,
      the reverse transcriptase domain of the polymerase was shown to be physically
      altered following binding to epsilon, as would be expected if the alteration was
      required for maturation of the polymerase to an enzymatically active form.
      Finally, analysis of 15 mutations throughout the duck hepatitis B virus
      polymerase demonstrated that the epsilon-dependent alteration to the polymerase
      was a prerequisite for DNA priming, reverse transcription, and the trans
      reaction.

PMID- 9621039
TI  - The interleukin-17 gene of herpesvirus saimiri.
AB  - In comparison to wild-type herpesvirus saimiri, viral interleukin-17 gene
      knockout mutants have unaltered behavior regarding viral replication, T-cell
      transformation in vitro, and pathogenicity in cottontop tamarins. Thus, this gene
      is not required for T-cell lymphoma induction but may contribute to apathogenic
      viral persistence in the natural host, the squirrel monkey.

PMID- 9621040
TI  - HveA (herpesvirus entry mediator A), a coreceptor for herpes simplex virus entry,
      also participates in virus-induced cell fusion.
AB  - The purpose of this study was to determine whether a cell surface protein that
      can serve as coreceptor for herpes simplex virus type 1 (HSV-1) entry,
      herpesvirus entry mediator (previously designated HVEM but renamed HveA), also
      mediates HSV-1-induced cell-cell fusion. We found that transfection of DNA from
      KOS-804, a previously described HSV-1 syncytial (Syn) strain whose Syn mutation
      was mapped to an amino acid substitution in gK, induced numerous large syncytia
      on HveA-expressing Chinese hamster ovary cells (CHO-HVEM12) but not on control
      cells (CHO-C8). Antibodies specific for gD as well as for HveA were effective
      inhibitors of KOS-804-induced fusion, consistent with previously described direct
      interactions between gD and HveA. Since mutations in gD determine the ability of
      HSV-1 to utilize HveA for entry, we examined whether the form of virally
      expressed gD also influenced the ability of HveA to mediate fusion. We produced a
      recombinant virus carrying the KOS-804 Syn mutation and the KOS-Rid1 gD mutation,
      which significantly reduces viral entry via HveA, and designated it KOS-SR1. KOS
      SR1 DNA had a markedly reduced ability to induce syncytia on CHO-HVEM12 cells and
      a somewhat enhanced ability to induce syncytia on CHO-C8 cells. These results
      support previous findings concerning the relative abilities of KOS and KOS-Rid1
      to infect CHO-HVEM12 and CHO-C8 cells. Thus, HveA mediates cell-cell fusion as
      well as viral entry and both activities of HveA are contingent upon the form of
      gD expressed by the virus.

PMID- 9621041
TI  - Rapamycin and wortmannin enhance replication of a defective encephalomyocarditis
      virus.
AB  - Inhibitors of the phosphatidylinositol 3-kinase (PI3 kinase)-FKBP-rapamycin
      associated protein (FRAP) pathway, such as rapamycin and wortmannin, induce
      dephosphorylation and activation of the suppressor of cap-dependent translation,
      4E-BP1. Encephalomyocarditis virus (EMCV) infection leads to activation of 4E-BP1
      at the time of host translation shutoff. Consistent with these data, rapamycin
      mildly enhances the synthesis of viral proteins and the shutoff of host cell
      protein synthesis after EMCV infection. In this study, two defective EMCV strains
      were generated by deleting portions of the 2A coding region of an infectious cDNA
      clone. These deletions dramatically decreased the efficiency of viral protein
      synthesis and abolished the virus-induced shutoff of host translation after
      infection of BHK-21 cells. Both translation and processing of the P1-2A capsid
      precursor polypeptide are impaired by the deletions in 2A. The translation and
      yield of mutant viruses were increased significantly by the presence of rapamycin
      and wortmannin during infection. Thus, inhibition of the PI3 kinase-FRAP
      signaling pathway partly complements mutations in 2A protein and reverses a slow
      virus phenotype.

PMID- 9621042
TI  - Role of the SH3-ligand domain of simian immunodeficiency virus Nef in interaction
      with Nef-associated kinase and simian AIDS in rhesus macaques.
AB  - The nef gene of the human and simian immunodeficiency viruses (HIV and SIV) is
      dispensable for viral replication in T-cell lines; however, it is essential for
      high virus loads and progression to simian AIDS (SAIDS) in SIV-infected adult
      rhesus macaques. Nef proteins from HIV type 1 (HIV-1), HIV-2, and SIV contain a
      proline-Xaa-Xaa-proline (PxxP) motif. The region of Nef with this motif is
      similar to the Src homology region 3 (SH3) ligand domain found in many cell
      signaling proteins. In virus-infected lymphoid cells, Nef interacts with a
      cellular serine/threonine kinase, designated Nef-associated kinase (NAK). In this
      study, analysis of viral clones containing point mutations in the nef gene of the
      pathogenic clone SIVmac239 revealed that several strictly conserved residues in
      the PxxP region were essential for Nef-NAK interaction. The results of this
      analysis of Nef mutations in in vitro kinase assays indicated that the PxxP
      region in SIV Nef was strikingly similar to the consensus sequence for SH3 ligand
      domains possessing the minus orientation. To test the significance of the PxxP
      motif of Nef for viral pathogenesis, each proline was mutated to an alanine to
      produce the viral clone SIVmac239-P104A/P107A. This clone, expressing Nef that
      does not associate with NAK, was inoculated into seven juvenile rhesus macaques.
      In vitro kinase assays were performed on virus recovered from each animal; the
      ability of Nef to associate with NAK was restored in five of these animals as
      early as 8 weeks after infection. Analysis of nef genes from these viruses
      revealed patterns of genotypic reversion in the mutated PxxP motif. These
      revertant genotypes, which included a second-site suppressor mutation, restored
      the ability of Nef to interact with NAK. Additionally, the proportion of
      revertant viruses increased progressively during the course of infection in these
      animals, and two of these animals developed fatal SAIDS. Taken together, these
      results demonstrated that in vivo selection for the ability of SIV Nef to
      associate with NAK was correlated with the induction of SAIDS. Accordingly, these
      studies implicate a role for the conserved SH3 ligand domain for Nef function in
      virally induced immunodeficiency.

PMID- 9621043
TI  - Genetically related human immunodeficiency virus type 1 in three adults of a
      family with no identified risk factor for intrafamilial transmission.
AB  - A small number of cases of human immunodeficiency virus (HIV) infection have been
      reported in individuals with no identified risk factors for transmission. We
      report on the seroconversion of the 61-year-old mother and the subsequent finding
      of HIV seropositivity in the 66-year-old father of a 31-year-old AIDS patient.
      Extensive investigation failed to identify any risk factor for intrafamilial
      transmission. We conducted a genetic analysis and determined the amino acid
      signature patterns of the V3, V4, and V5 hypervariable domains and flanking
      regions in the HIV-1 gp120 env gene of 26 clones derived from proviral DNA in
      peripheral blood mononuclear cells of the members of the family. env sequences of
      the viruses isolated from the patients were compared with sequences of HIV-1
      subtype B viruses from Europe and local field isolates. Phylogenetic analysis
      revealed that the sequences of the viruses isolated from the patients were
      genetically related and formed an intrafamilial cluster of HIV-1 distinct from
      other subtype B viruses. Interindividual nucleotide variability in the C2-V3 and
      V4-C4-V5 domains ranged between 1.2 and 5.0% and between 2.2 and 7.5%,
      respectively, whereas divergence between HIV strains from the patients and
      control viral strains ranged from 6.6 to 29.3%. The amino acid signature patterns
      of viral clones from the three patients were closely related. In the C2-V3
      region, two minor clones derived from the son's virus showed less nucleotide
      divergence (mean, 3.5 and 3.9%) than did the clones derived from the viruses of
      both parents or the seven other predominant clones derived from the virus from
      the son (mean, 5.4%). The top of the V3 loop of the last two clones and of all
      viral clones from the parents exhibited an unusual GPGG sequence. This is the
      first report of genotypic relatedness of HIV-1 in three adults of the same family
      in the absence of identified risk factor for transmission between the members of
      the family. Our findings suggest that atypical transmission of HIV may occur.

PMID- 9621044
TI  - Substitutions in a major histocompatibility complex class II-restricted human
      immunodeficiency virus type 1 gp120 epitope can affect CD4+ T-helper-cell
      function.
AB  - It has been suggested that the inability of the immune response to control human
      immunodeficiency virus type 1 (HIV-1) replication may be due, at least in part,
      to the capacity of this virus to escape from immune recognition through mutation.
      While there is increasing evidence for the importance of HIV-1-specific CD4+ T
      cells in containing HIV-1 spread in the infected individual, little is known
      about the consequences of HIV-1 mutation on virus-specific CD() T-cell function.
      The impact of HIV-1 sequence variation on CD4+ T-helper (Th)- cell function was
      assessed with a rhesus monkey model for immune recognition of the HIV-1 envelope
      (Env) glycoprotein. A series of HIV-1 Env(484-496) variant peptides were shown to
      retain the ability to bind to the appropriate rhesus monkey major
      histocompatibility complex class II DR molecule. Peptides bearing substitutions
      at position 490, however, failed to drive the proliferation or cytokine secretion
      of two well-characterized HXBc2 Env-specific rhesus monkey CD4+ Th-cell lines.
      Exogenous costimulation was ineffective in complementing the ability of the
      nonstimulatory peptides to induce [3H]thymidine incorporation by these cells.
      Finally, HIV-1 Env(484-496) variant peptides with substitutions at position 490
      antagonized the HXBc2 Env peptide-induced proliferative response of the CD4+ Th
      cell lines. Thus, HIV-1 variants appear to have the capacity to neutralize the
      function of virus-specific CD4+ T lymphocytes.

PMID- 9621045
TI  - Uncoupled expression of p33 and p92 permits amplification of tomato bushy stunt
      virus RNAs.
AB  - Tomato bushy stunt virus (TBSV) is a plus-sense RNA virus which encodes a 33-kDa
      protein in its 5'-most open reading frame (ORF). Readthrough of the amber stop
      codon of the p33 ORF results in the production of a 92-kDa fusion protein. Both
      of these products are expressed directly from the viral genome and are suspected
      to be involved in viral RNA replication. We have investigated further the roles
      of these proteins in the amplification of viral RNAs by using a complementation
      system in which p33 and p92 are expressed from different viral RNAs. Our results
      indicate that (i) both of these proteins are necessary for viral RNA
      amplification; (ii) translation of these proteins can be uncoupled while
      maintaining amplification of viral RNAs; (iii) if compatibility requirements
      exist between p33 and p92, they are not exceptionally strict; and (iv) the C
      terminal approximately 6% of p33 is necessary for its functional activity.
      Interestingly, no complementation was observed when a p33-encoding replicon
      containing a deletion of a 3'-located segment, region 3.5, was tested. However,
      when 5'-capped transcripts of the same replicon were analyzed, complementation
      allowing for RNA amplification was observed. This ability to compensate
      functionally for the absence of region 3.5 by the addition of a 5' cap suggests
      that this RNA segment may act as a translational enhancer for the expression of
      virally encoded products.

PMID- 9621046
TI  - Contact with thymic epithelial cells as a prerequisite for cytokine-enhanced
      human immunodeficiency virus type 1 replication in thymocytes.
AB  - We report here that human immunodeficiency virus type 1 (HIV-1)-infected human
      thymocytes, in the absence of any exogenous stimulus but cocultivated with
      autologous thymic epithelial cells (TEC), obtained shortly (3 days) after thymus
      excision produce a high and sustained level of HIV-1 particles. The levels and
      kinetics of HIV-1 replication were similar for seven distinct viral strains
      irrespective of their phenotypes and genotypes. Contact of thymocytes with TEC is
      a critical requirement for optimal viral replication. Rather than an inductive
      signal resulting from the contact itself, soluble factors produced in the mixed
      culture are responsible for this effect. Specifically, the synergistic effects of
      tumor necrosis factor, interleukin-1 (IL-1), IL-6, and granulocyte-macrophage
      colony-stimulating factor may account by themselves for the high level of HIV-1
      replication in thymocytes observed in mixed cultures. In conclusion, the
      microenvironment generated by TEC-thymocyte interaction might greatly favor
      optimal HIV-1 replication in the thymus.

PMID- 9621047
TI  - Retinoid-induced repression of human immunodeficiency virus type 1 core promoter
      activity inhibits virus replication.
AB  - The rates of mother-to-child transmission of human immunodeficiency virus type 1
      (HIV-1), progression to AIDS following HIV-1 infection, and AIDS-associated
      mortality are all inversely correlated with serum vitamin A levels (R. D. Semba,
      W. T. Caiaffa, N. M. H. Graham, S. Cohn, and D. Vlahov, J. Infect. Dis. 171:1196
      1202, 1995; R. D. Semba, N. M. H. Graham, W. T. Caiaffa, J. B. Margolik, L.
      Clement, and D. Vlahov, Arch. Intern. Med. 153:2149-2154, 1993; R. D. Semba, P.
      G. Miotti, J. D. Chiphangwi, A. J. Saah, J. K. Canner, G. A. Dallabetta, and D.
      R. Hoover, Lancet 343:1593-1596, 1994). Here we show that physiological
      concentrations of vitamin A, as retinol or as its metabolite, all-trans retinoic
      acid, repressed HIV-1Ba-L replication in monocyte-derived macrophages (MDMs).
      Repression required retinoid treatment of peripheral monocytes during their in
      vitro differentiation into MDMs. Retinoids had no repressive effect if they were
      added after virus infection. Retinol, as well as all-trans retinoic acid and 9
      cis retinoic acid, also repressed HIV-1 long terminal repeat (LTR)-directed
      expression up to 200-fold in transfected THP-1 monocytes. Analysis of HIV-1 LTR
      deletion mutants demonstrated that retinoids were able to repress activation of
      HIV-1 expression by both NF-kappaB and Tat. A cis-acting sequence required for
      retinoid-mediated repression of HIV-1 transcription was localized between
      nucleotides -51 and +12 of the HIV-1 LTR within the core promoter. Protein-DNA
      cross-linking experiments identified four proteins specific to retinoid-treated
      cells that bound to the core promoter. We conclude that retinoids render
      macrophages resistant to virus replication by modulating the interaction of
      cellular transcription factors with the viral core promoter.

PMID- 9621048
TI  - Genes required for replication of the 15.5-kilobase RNA genome of a plant
      closterovirus.
AB  - A full-length cDNA clone of beet yellows closterovirus (BYV) was engineered and
      used to map functions involved in the replication of the viral RNA genome and
      subgenomic RNA formation. Among 10 open reading frames (ORFs) present in BYV,
      ORFs 1a and 1b suffice for RNA replication and transcription. The proteins
      encoded in these ORFs harbor putative methyltransferase, RNA helicase, and RNA
      polymerase domains common to Sindbis virus-like viruses and a large interdomain
      region that is unique to closteroviruses. The papain-like leader proteinase (L
      Pro) encoded in the 5'-proximal region of ORF 1a was found to have a dual
      function in genome amplification. First, the autocatalytic cleavage between L-Pro
      and the remainder of the ORF 1a product was essential for replication of RNA.
      Second, an additional L-Pro function that was separable from proteolytic activity
      was required for efficient RNA accumulation. The deletion of a large,
      approximately 5.6-kb, 3'-terminal region coding for a 6-kDa hydrophobic protein,
      an HSP70 homolog, a 64-kDa protein, minor and major capsid proteins, a 20-kDa
      protein, and a 21-kDa protein (p21) resulted in replication-competent RNA.
      However, examination of mutants with replacements of start codons in each of
      these seven 3'-terminal ORFs revealed that p21 functions as an enhancer of genome
      amplification. The intriguing analogies between the genome organization and
      replicational requirements of plant closteroviruses and animal coronavirus-like
      viruses are discussed.

PMID- 9621049
TI  - Nonreciprocal packaging of human immunodeficiency virus type 1 and type 2 RNA: a
      possible role for the p2 domain of Gag in RNA encapsidation.
AB  - The ability of human immunodeficiency virus types 1 (HIV-1) and 2 (HIV-2) to
      cross-package each other's RNA was investigated by cotransfecting helper virus
      constructs with vectors derived from both viruses from which the gag and pol
      sequences had been removed. HIV-1 was able to package both HIV-1 and HIV-2 vector
      RNA. The unspliced HIV-1 vector RNA was packaged preferentially over spliced RNA;
      however, unspliced and spliced HIV-2 vector RNA were packaged in proportion to
      their cytoplasmic concentrations. The HIV-2 helper virus was unable to package
      the HIV-1 vector RNA, indicating a nonreciprocal RNA packaging relationship
      between these two lentiviruses. Chimeric proviruses based on HIV-2 were
      constructed to identify the regions of the HIV-1 Gag protein conferring RNA
      packaging specificity for the HIV-1 packaging signal. Two chimeric viruses were
      constructed in which domains within the HIV-2 gag gene were replaced by the
      corresponding domains in HIV-1, and the ability of the chimeric proviruses to
      encapsidate an HIV-1-based vector was studied. Wild-type HIV-2 was unable to
      package the HIV-1-based vector; however, replacement of the HIV-2 nucleocapsid by
      that of HIV-1 generated a virus with normal protein processing which could
      package the HIV-1-based vector. The chimeric viruses retained the ability to
      package HIV-2 genomic RNA, providing further evidence for a lack of reciprocity
      in RNA-packaging ability between the HIV-1 and HIV-2 nucleocapsid proteins.
      Inclusion of the p2 domain of HIV-1 Gag in the chimera significantly enhanced
      packaging.

PMID- 9621050
TI  - Functional analysis of the core human immunodeficiency virus type 1 packaging
      signal in a permissive cell line.
AB  - Packaging of type C retrovirus genomic RNAs into budding virions requires a
      highly specific interaction between the viral Gag precursor and unique cis-acting
      packaging signals on the full-length RNA genome, allowing the selection of this
      RNA species from among a pool of spliced viral RNAs and similar cellular RNAs.
      This process is thought to involve RNA secondary and tertiary structural motifs
      since there is little conservation of the primary sequence of this region between
      retroviruses. To confirm RNA secondary structures, which we and others have
      predicted for this region, disruptive, compensatory, and deletion mutations were
      introduced into proviral constructs, which were then assayed in a permissive cell
      line. Disruption of either of two predicted stem-loops was found to greatly
      reduce RNA encapsidation and replication, whereas compensatory mutations
      restoring base pairing to these stem-loops had a wild-type phenotype. A GGNGR
      motif was identified in the loops of three hairpins in this region. Results were
      consistent with the hypothesis that the process of efficient RNA encapsidation is
      linked to dimerization. Replication and encapsidation were shown to occur at a
      reduced rate in the absence of the previously described kissing hairpin motif.

PMID- 9621051
TI  - Antiapoptotic activity of the herpesvirus saimiri-encoded Bcl-2 homolog:
      stabilization of mitochondria and inhibition of caspase-3-like activity.
AB  - Viruses have evolved different strategies to interfere with host cell apoptosis.
      Herpesvirus saimiri (HVS) and other lymphotropic herpesviruses code for proteins
      that are homologous to the cellular antiapoptotic Bcl-2. In this study HVS-Bcl-2
      was stably expressed in the human leukemia cell line Jurkat and in the murine T
      cell hybridoma DO to assess its antiapoptotic spectrum and to gain further
      insight into its mode of action. HVS- Bcl-2 prevented apoptosis that occurs as a
      result of a disturbance of intracellular homeostasis by, for example, DNA damage
      or menadione, which gives rise to oxygen radicals. In Jurkat cells, HVS-Bcl-2
      also inhibited apoptosis mediated by the death receptor CD95. In DO cells, HVS
      Bcl-2 did not interfere with CD95-mediated apoptosis but blocked dexamethasone
      induced cell death. Mitochondrial damage is a central coordinating event in
      apoptosis induced by different stimuli. To assess the integrity of mitochondria,
      we used rhodamine 123, which is released upon disturbance of the mitochondrial
      membrane potential, and determined the release of cytochrome c into the cytosol.
      Both signs of mitochondrial damage were prevented by HVS-Bcl-2. This viral
      protein also inhibited the generation of caspase-3-like DEVDase activity and
      blocked the cleavage of poly(ADP-ribose) polymerase, a natural substrate of
      caspase-3-like proteases. In conclusion, HVS-Bcl-2 protects against a great
      variety of apoptotic stimuli, stabilizes mitochondria, and acts upstream of the
      generation of caspase-3-like activity.

PMID- 9621052
TI  - Replication defect of moloney murine leukemia virus with a mutant reverse
      transcriptase that can incorporate ribonucleotides and deoxyribonucleotides.
AB  - Reverse transcriptase (RT) plays a critical role in retrovirus replication,
      directing the synthesis of a double- stranded DNA copy of the viral RNA genome.
      We have previously described a mutant RT of the Moloney murine leukemia virus in
      which F155 was replaced by valine, and we demonstrated that this substitution
      allowed the enzyme to incorporate ribonucleotides to form RNA while still
      retaining its normal ability to incorporate deoxyribonucleotides to form DNA.
      When introduced into the viral genome, this mutation rendered the virus incapable
      of replication. Characterization of the mutant virus revealed that the enzyme was
      still active and able to synthesize minus-strand strong stop DNA and some longer
      products but failed to make full-length minus-strand DNA. We propose that the
      failure of the enzyme to complete DNA synthesis in vivo resulted from its ability
      to incorporate ribonucleotides into the products, which served as inhibitors for
      DNA synthesis. We also tested seven other amino acid residues for their abilities
      to substitute for F155 in virus replication; of these, only tyrosine could
      support virus replication. In an attempt to select for second-site suppressor
      mutations, the F155V mutant was subjected to random mutagenesis and was used as a
      parent for the isolation of revertant viruses. Two independent revertants were
      found to have changed the valine residue at position 155 back to the wild- type
      phenylalanine. These results suggest that an aromatic ring at this position is
      important for virus replication.

PMID- 9621053
TI  - Infection with cytotoxic T-lymphocyte escape mutants results in increased
      mortality and growth retardation in mice infected with a neurotropic coronavirus.
AB  - C57BL/6 mice infected with mouse hepatitis virus strain JHM (MHV-JHM) develop a
      chronic demyelinating encephalomyelitis several weeks after inoculation.
      Previously, we showed that mutations in the immunodominant CD8 T-cell epitope (S
      510-518) could be detected in nearly all samples of RNA and virus isolated from
      these mice. These mutations abrogated recognition by T cells harvested from the
      central nervous systems of infected mice in direct ex vivo cytotoxicity assays.
      These results suggested that cytotoxic T-lymphocyte (CTL) escape mutants
      contributed to virus amplification and the development of clinical disease in
      mice infected with wild-type virus. In the present study, the importance of these
      mutations was further evaluated by infecting naive mice with MHV-JHM variants
      isolated from infected mice and in which epitope S-510-518 was mutated. Compared
      to mice infected with wild-type virus, variant virus-infected animals showed
      higher mortality and morbidity manifested by decreased weight gain and
      neurological signs. Although a delay in the kinetics of virus clearance has been
      demonstrated in previous studies of CTL escape mutants, this is the first
      illustration of significant changes in clinical disease resulting from infection
      with viruses able to evade the CD8 T-cell immune response.

PMID- 9621054
TI  - Adeno-associated virus vector-mediated transgene integration into neurons and
      other nondividing cell targets.
AB  - The site-specific integration of wild-type adeno-associated virus (wtAAV) into
      the human genome is a very attractive feature for the development of AAV-based
      gene therapy vectors. However, knowledge about integration of wtAAV, as well as
      currently configured recombinant AAV (rAAV) vectors, is limited. By using a
      modified Alu-PCR technique to amplify and sequence the vector-cellular junctions,
      we provide the first direct evidence both in vitro and in vivo of rAAV-mediated
      transgene integration in several types of nondividing cells, including neurons.
      This novel technique will be highly useful for further delineating the mechanisms
      underlying AAV-mediated integration, including issues of frequency, site
      preference, and DNA rearrangement in human as well as animal cells. Results from
      these studies should be beneficial for the development of the next generation of
      gene delivery vectors.

PMID- 9621055
TI  - Characterization of drug resistance-associated mutations in the human
      cytomegalovirus DNA polymerase gene by using recombinant mutant viruses generated
      from overlapping DNA fragments.
AB  - A number of specific point mutations in the human cytomegalovirus (HCMV) DNA
      polymerase (UL54) gene have been tentatively associated with decreased
      susceptibility to antiviral agents and consequently with clinical failure. To
      precisely determine the roles of UL54 mutations in HCMV drug resistance,
      recombinant UL54 mutant viruses were generated by using cotransfection of nine
      overlapping HCMV DNA fragments into permissive fibroblasts, and their drug
      susceptibility profiles were determined. Amino acid substitutions located in UL54
      conserved region IV (N408D, F412C, and F412V), region V (A987G), and delta-region
      C (L501I, K513E, P522S, and L545S) conferred various levels of resistance to
      cidofovir and ganciclovir. Mutations in region II (T700A and V715M) and region VI
      (V781I) were associated with resistance to foscarnet and adefovir. The region II
      mutations also conferred moderate resistance to lobucavir. In contrast to
      mutations in other UL54 conserved regions, those residing specifically in region
      III (L802M, K805Q, and T821I) were associated with various drug susceptibility
      profiles. Mutations located outside the known UL54 conserved regions (S676G and
      V759M) did not confer any significant changes in HCMV drug susceptibility.
      Predominantly an additive effect of multiple UL54 mutations with respect to the
      final drug resistance phenotype was demonstrated. Finally, the influence of
      selected UL54 mutations on the susceptibility of viral DNA replication to
      antiviral drugs was characterized by using a transient-transfection-plus
      infection assay. Results of this work exemplify specific roles of the UL54
      conserved regions in the development of HCMV drug resistance and may help guide
      optimization of HCMV therapy.

PMID- 9621057
TI  - Fas ligand-mediated lysis of self bystander targets by human papillomavirus
      specific CD8+ cytotoxic T lymphocytes.
AB  - Mouse cytotoxic T lymphocytes (CTL) reactive with a H-2Db-presented 9-mer peptide
      of the human papillomavirus type 16 protein E7(49-57) (RAHYNIVTF) were generated
      from the spleen cells of wild-type C57BL/6 (B6) or B6 perforin-deficient (B6.P0)
      mice. CD8(+) B6 CTL displayed peptide-specific perforin- and Fas-mediated lysis
      of E7-transfected mouse RMA lymphoma cells (RMA-E7), while CD8(+) CTL from B6.P0
      mice lysed RMA-E7 cells via Fas ligand (FasL) exclusively. Rapid and efficient
      lysis of syngeneic bystander B6 blasts or RMA cells by either B6 or B6.P0 Ag
      activated CTL was mediated by a FasL-Fas mechanism. Fas-resistant bystanders were
      not lysed, nor were allogeneic Fas-sensitive C3H/HeJ (H-2(k)) or BALB/c (H-2(d))
      bystander blasts. Interestingly, however, phorbol myristate acetate-ionomycin
      preactivation of B6.P0 effectors enabled lysis of allogeneic H-2(k) and H-2(d)
      bystanders even in the absence of antigenic stimulation. Lysis of syngeneic
      bystander cells was always FasL-Fas dependent and required effector-bystander
      contact and, in particular, an interaction between CTL LFA-1 and bystander ICAM
      1. Thus, in the context of major histocompatibility complex class I molecule
      peptide ligation of the T-cell receptors of CD8(+) CTL, neighboring bystander
      cells that are syngeneic and Fas sensitive and express the adhesion molecule ICAM
      1 are potential targets of CTL attack.

PMID- 9621056
TI  - Examination of the kinetics of herpes simplex virus glycoprotein D binding to the
      herpesvirus entry mediator, using surface plasmon resonance.
AB  - Previously, we showed that truncated soluble forms of herpes simplex virus (HSV)
      glycoprotein D (gDt) bound directly to a truncated soluble form of the
      herpesvirus entry mediator (HveAt, formerly HVEMt), a cellular receptor for HSV.
      The purpose of the present study was to determine the affinity of gDt for HveAt
      by surface plasmon resonance and to compare and contrast the kinetics of an
      expanded panel of gDt variants in binding to HveAt in an effort to better
      understand the mechanism of receptor binding and virus entry. Both HveAt and gDt
      are dimers in solution and interact with a 2:1 stoichiometry. With HveAt,
      gD1(306t) (from the KOS strain of HSV-1) had a dissociation constant (KD) of 3.2
      x 10(-6) M and gD2(306t) had a KD of 1.5 x 10(-6) M. The interaction between gDt
      and HveAt fits a 1:1 Langmuir binding model, i.e., two dimers of HveAt may act as
      one binding unit to interact with one dimer of gDt as the second binding unit. A
      gD variant lacking all signals for N-linked oligosaccharides had an affinity for
      HveAt similar to that of gD1(306t). A variant lacking the bond from cysteine 1 to
      cysteine 5 had an affinity for HveAt that did not differ from that of the wild
      type. However, variants with double cysteine mutations that eliminated either of
      the other two disulfide bonds showed decreased affinity for HveAt. This result
      suggests that two of the three disulfide bonds of gD are important for receptor
      binding. Four nonfunctional gDt variants, each representing one functional domain
      of gD, were also studied. Mutations in functional regions I and II drastically
      decreased the affinity of gDt for HveAt. Surprisingly, a variant with an
      insertion in functional region III had a wild-type level of affinity for HveAt,
      suggesting that this domain may function in virus entry at a step other than
      receptor binding. A variant with a deletion in functional region IV [gD1(Delta290
      299t)] exhibited a 100-fold enhancement in affinity for HveAt (KD = 3.3 x 10(-8)
      M) due mainly to a 40-fold increase in its kinetic on rate. This agrees with the
      results of other studies showing the enhanced ability of gD1(Delta290-299t) to
      block infection. Interestingly, all the variants with decreased affinities for
      HveAt exhibited decreased kinetic on rates but only minor changes in their
      kinetic off rates. The results suggest that once the complex between gDt and
      HveAt forms, its stability is unaffected by a variety of changes in gD.

PMID- 9621058
TI  - Retroviral diversity and distribution in vertebrates.
AB  - We used the PCR to screen for the presence of endogenous retroviruses within the
      genomes of 18 vertebrate orders across eight classes, concentrating on reptilian,
      amphibian, and piscine hosts. Thirty novel retroviral sequences were isolated and
      characterized by sequencing approximately 1 kb of their encoded protease and
      reverse transcriptase genes. Isolation of novel viruses from so many disparate
      hosts suggests that retroviruses are likely to be ubiquitous within all but the
      most basal vertebrate classes and, furthermore, gives a good indication of the
      overall retroviral diversity within vertebrates. Phylogenetic analysis
      demonstrated that viruses clustering with (but not necessarily closely related
      to) the spumaviruses and murine leukemia viruses are widespread and abundant in
      vertebrate genomes. In contrast, we were unable to identify any viruses from
      hosts outside of mammals and birds which grouped with the other five currently
      recognized retroviral genera: the lentiviruses, human T-cell leukemia-related
      viruses, avian leukemia virus-related retroviruses, type D retroviruses, and
      mammalian type B retroviruses. There was also some indication that viruses
      isolated from individual vertebrate classes tended to cluster together in
      phylogenetic reconstructions. This implies that the horizontal transmission of at
      least some retroviruses, between some vertebrate classes, occurs relatively
      infrequently. It is likely that many of the retroviral sequences described here
      are distinct enough from those of previously characterized viruses to represent
      novel retroviral genera.

PMID- 9621059
TI  - Encapsidation of the flavivirus kunjin replicon RNA by using a complementation
      system providing Kunjin virus structural proteins in trans.
AB  - Kunjin virus (KUN) replicon RNA was encapsidated by a procedure involving two
      consecutive electroporations of BHK-21 cells, first with KUN replicon RNA
      C20DXrep (with prME and most of C deleted) and about 24 h later with a
      recombinant Semliki Forest virus (SFV) replicon RNA(s) expressing KUN structural
      proteins. The presence of KUN replicon RNA in encapsidated particles was
      demonstrated by its amplification and expression in newly infected BHK-21 cells,
      detected by Northern blotting with a KUN-specific probe and by immunofluorescence
      analysis with anti-NS3 antibodies. No infectious particles were produced when
      C20DXrep RNA and recombinant SFV RNAs were electroporated simultaneously. When
      the second electroporation was performed with a single SFV replicon RNA
      expressing the KUN contiguous prME genes and the KUN C gene together but under
      control of two separate 26S subgenomic promoters (SFV-prME-C107), a 10-fold
      higher titer of infectious particles was achieved than when two different SFV
      replicon RNAs expressing the KUN C gene (SFV-C107) and prME genes (SFV-prME)
      separately were used. No SFV replicon RNAs expressing KUN structural proteins
      were encapsidated in secreted particles. Infectious particles pelleted by
      ultracentrifugation of the culture fluid from cells sequentially transfected with
      C20DXrep and SFV-prME-C107 RNAs were neutralized by preincubation with monoclonal
      antibodies to KUN E protein. Radioimmunoprecipitation analysis with anti-E
      antibodies of the culture fluid of the doubly transfected cells showed the
      presence of C, prM/M, and E proteins in the immunoprecipitated particles. Reverse
      transcription-PCR analysis showed that the immunoprecipitated particles also
      contained KUN-specific RNA. The encapsidated replicon particles sedimented more
      slowly than KUN virions in a 5 to 25% sucrose density gradient and were uniformly
      spherical, with an approximately 35-nm diameter, compared with approximately 50
      nm for KUN virions. The results of this study demonstrate for the first time
      packaging of flavivirus RNA in trans, and they exclude a role in packaging for
      virtually all of the structural region. Possible applications of the developed
      packaging system include the definition of the packaging signal(s) in flavivirus
      RNA as well as the amino acid motif(s) in the structural proteins involved in RNA
      encapsidation, virion assembly, and secretion. Furthermore, it could facilitate
      the development of a noninfectious vaccine delivery system based on encapsidation
      of a noncytopathic flavivirus replicon expressing heterologous genes.

PMID- 9621060
TI  - AR1 is an integral part of the adenovirus type 2 E1A-CR3 transactivation domain.
AB  - We have previously shown that the nonconserved carboxy-terminal exon of the
      adenovirus type 2 E1A-289R protein contains two interchangeable sequence
      elements, auxiliary region (AR) 1 and AR2, that are required for efficient CR3
      mediated transcriptional activation of the viral E4 promoter (M. Bondesson, C.
      Svensson, S. Linder, and G. Akusjarvi, EMBO J. 11:3347-3354, 1992). Here we show
      that CR3-mediated transactivation of all adenovirus early promoters and the HSP70
      promoter requires the AR1 element. We further show that AR2 can substitute for
      AR1 only when artificially juxtaposed to CR3. AR1 consists of six tandem glutamic
      acid-proline (EP) repeats and is positioned immediately downstream of CR3.
      Genetic dissection of AR1 showed that the number of EP repeats in AR1 is critical
      for CR3 function. Thus, reducing or increasing the number of EP repeats reduces
      the CR3 transactivation capacity. Furthermore, the introduction of amino acid
      substitutions into AR1 suggested that the net negative charge in AR1 is of
      critical importance for its function as an enhancer of CR3-mediated
      transcriptional activation. Using an in vitro binding approach, we showed that
      the AR1 element is not part of the CR3 promoter localization signal mediating
      contact with the Sp1, ATF-2, or c-Jun upstream-binding transcription factors.
      Previous studies have suggested that the 49-amino-acid sequence constituting CR3
      represents the minimal domain required for E1A-induced activation of viral early
      promoters. Since AR1 was required for efficient CR3-mediated transcriptional
      activation of all tested promoters, we suggest that the carboxy-terminal boundary
      for the CR3 transactivation domain should be extended to include the AR1 element.

PMID- 9621061
TI  - The various Sendai virus C proteins are not functionally equivalent and exert
      both positive and negative effects on viral RNA accumulation during the course of
      infection.
AB  - Recombinant Sendai viruses were prepared which cannot express their Cprime, C, or
      Cprime plus C proteins due to mutation of their respective start codons ([Cprime
      minus], [C-minus] and [double mutant], respectively). The [Cprime-minus] and [C
      minus] stocks were similar to that of wild-type (wt) virus in virus titer and
      plaque formation, whereas the double-mutant stock had a much-reduced PFU or 50%
      egg infective dose/particle ratio and produced very small plaques. Relative to
      the wt virus infection, the [Cprime-minus] and [C-minus] infections of BHK cells
      resulted in significantly greater accumulation of viral RNAs, consistent with the
      known inhibitory effects of the Cprime and C proteins. The double-mutant
      infection, in contrast, was delayed in its accumulation of viral RNAs; however,
      once accumulation started, overaccumulation quickly occurred, as in the single
      mutant infections. Our results suggest that the Cprime and C proteins both
      provide a common positive function early in infection, so that only the double
      mutant undergoes delayed RNA accumulation and exhibits the highly debilitated
      phenotype. Later in infection, the same proteins appear to act as inhibitors of
      RNA accumulation. In infections of mice, [Cprime-minus] was found to be as
      virulent as wt virus whereas [C-minus] was highly attenuated. These results
      suggest that the Cprime and C proteins cannot be functionally equivalent, since C
      can replace Cprime for virulence in mice whereas Cprime cannot replace C.

PMID- 9621062
TI  - In vivo protein binding and functional analysis of cis-acting elements in the U3
      region of the bovine leukemia virus long terminal repeat.
AB  - Bovine leukemia virus (BLV) is a member of the human T-cell leukemia virus
      (HTLV)/BLV group of retroviruses. These viruses regulate their own transcription
      by producing Tax, a protein which activates the virus promoter region, the long
      terminal repeat (LTR). To explore the molecular mechanisms involved in the
      transactivation, we identified protein binding elements by in vivo footprinting
      and analyzed their function by site- directed mutagenesis. We used in vivo
      dimethyl sulfate footprinting by ligation-mediated PCR to detect constitutive in
      vivo protein-DNA interactions in a BLV-producing cell line, Bat2Cl6. The U3
      region and part of the R region of the LTR were footprinted. In addition to the
      cis-acting elements (three cyclic AMP-responsive elements [CREs] and two AP4
      sites) reported by others to be important for Tax-mediated activation of the BLV
      LTR, we found footprints in regions flanking these elements and in the core
      promoter region. The importance of these sites for transcriptional activation was
      studied by site-directed mutagenesis followed by promoter function analysis of
      the mutants with a chloramphenicol acetyltransferase reporter system. Our data
      corroborate those of others showing that the CREs are necessary for
      transactivation of the LTR, and they identify two new functional sites not
      previously reported by others. We show that the middle region of the BLV U3
      contains multiple dual-functioning cis-acting elements which act as either
      positive or negative regulatory elements depending on the cell type tested. This
      is the first report of a functional mapping of the cis-acting elements of a virus
      of the HTLV/BLV group.

PMID- 9621063
TI  - Interaction of the human immunodeficiency virus type 1 Vpr protein with the
      nuclear pore complex.
AB  - The Vpr protein of human immunodeficiency virus type 1 (HIV-1) performs a number
      of functions that are associated with the nucleus. Vpr enhances the nuclear
      import of postentry viral nucleoprotein complexes, arrests proliferating cells in
      the G2 phase of the cell cycle, and acts as a modest transcriptional activator.
      For this paper, we have investigated the nuclear import of Vpr. Although Vpr does
      not encode a sequence that is recognizable as a nuclear localization signal
      (NLS), Vpr functions as a transferable NLS both in somatic cells and in Xenopus
      laevis oocytes. In certain contexts, Vpr also mediates substantial accumulation
      at the nuclear envelope and, in particular, at nuclear pore complexes (NPCs).
      Consistent with this, Vpr is shown to interact specifically with nucleoporin
      phenylalanine-glycine (FG)-repeat regions. These findings not only demonstrate
      that Vpr harbors a bona fide NLS but also raise the possibility that one (or
      more) of Vpr's functions may take place at the NPC.

PMID- 9621064
TI  - Limited entry of adenovirus vectors into well-differentiated airway epithelium is
      responsible for inefficient gene transfer.
AB  - Investigations of the efficiency and safety of human adenovirus vector (AdV)
      mediated gene transfer in the airways of patients with cystic fibrosis (CF) in
      vivo have demonstrated little success in correcting the CF bioelectrical
      functional defect, reflecting the inefficiency of AdV-mediated gene transfer to
      the epithelial cells that line the airway luminal surface. In this study, we
      demonstrate that low AdV-mediated gene transfer efficiency to well-differentiated
      (WD) cultured airway epithelial cells is due to three distinct steps in the
      apical membrane of the airway epithelial cells: (i) the absence of specific
      adenovirus fiber-knob protein attachment receptors; (ii) the absence of
      alphavbeta3/5 integrins, reported to partially mediate the internalization of AdV
      into the cell cytoplasm; and (iii) the low rate of apical plasma membrane uptake
      pathways of WD airway epithelial cells. Attempts to increase gene transfer
      efficiency by increasing nonspecific attachment of AdV were unsuccessful,
      reflecting the inability of the attached vector to enter (penetrate) WD cells via
      nonspecific entry paths. Strategies to improve the efficiency of AdV for the
      treatment of CF lung disease will require methods to increase the attachment of
      AdV to and promote its internalization into the WD respiratory epithelium.

PMID- 9621065
TI  - Particle polymorphism caused by deletion of a peptide molecular switch in a
      quasiequivalent icosahedral virus.
AB  - The capsid of flock house virus is composed of 180 copies of a single type of
      coat protein which forms a T=3 icosahedral shell. High-resolution structural
      analysis has shown that the protein subunits, although chemically identical, form
      different contacts across the twofold axes of the virus particle. Subunits that
      are related by icosahedral twofold symmetry form flat contacts, whereas subunits
      that are related by quasi-twofold symmetry form bent contacts. The flat contacts
      are due to the presence of ordered genomic RNA and an ordered peptide arm which
      is inserted in the groove between the subunits and prevents them from forming the
      dihedral angle observed at the bent quasi-twofold contacts. We hypothesized that
      by deleting the residues that constitute the ordered peptide arm, formation of
      flat contacts should be impossible and therefore result in assembly of particles
      with only bent contacts. Such particles would have T=1 symmetry. To test this
      hypothesis we generated two deletion mutants in which either 50 or 31 residues
      were eliminated from the N terminus of the coat protein. We found that in the
      absence of residues 1 to 50, assembly was completely inhibited, presumably
      because the mutation removed a cluster of positively charged amino acids required
      for neutralization of encapsidated RNA. When the deletion was restricted to
      residues 1 to 31, assembly occurred, but the products were highly heterogeneous.
      Small bacilliform-like structures and irregular structures as well as wild-type
      like T=3 particles were detected. The anticipated T=1 particles, on the other
      hand, were not observed. We conclude that residues 20 to 30 are not critical for
      formation of flat protein contacts and formation of T=3 particles. However, the N
      terminus of the coat protein appears to play an essential role in regulating
      assembly such that only one product, T=3 particles, is synthesized.

PMID- 9621066
TI  - Functional replacement of the intracellular region of the Notch1 receptor by
      Epstein-Barr virus nuclear antigen 2.
AB  - The intracellular region (RAMIC) of the mouse Notch1 receptor interacts with RBP
      J/CBF-1, which binds to the DNA sequence CGTGGGAA and suppresses differentiation
      by transcriptional activation of genes regulated by RBP-J. Epstein-Barr virus
      nuclear antigen 2 (EBNA2) is essential for immortalization of human B cells by
      the virus. EBNA2 is a pleiotropic activator of viral and cellular genes and is
      targeted to DNA at least in part by interacting with RBP-J. We found that EBNA2
      and the Notch1 RAMIC compete for binding to RBP-J, indicating that their
      interaction sites on RBP-J overlap at least partially. EBNA2 and Notch1 RAMIC
      transactivated the same set of viral and host promoters, i.e., the EBNA2 response
      element of the Epstein-Barr virus TP1 and the HES-1 promoter. Furthermore, EBNA2
      functionally replaced the Notch1 RAMIC by suppressing differentiation of C2C12
      myoblast progenitor cells.

PMID- 9621067
TI  - Exclusive and persistent use of the entry coreceptor CXCR4 by human
      immunodeficiency virus type 1 from a subject homozygous for CCR5 delta32.
AB  - Individuals who are homozygous for the 32-bp deletion in the gene coding for the
      chemokine receptor and major human immunodeficiency virus type 1 (HIV-1)
      coreceptor CCR5 (CCR5 -/-) lack functional cell surface CCR5 molecules and are
      relatively resistant to HIV-1 infection. HIV-1 infection in CCR5 -/- individuals,
      although rare, has been increasingly documented. We now report that the viral
      quasispecies from one such individual throughout disease is homogenous, T cell
      line tropic, and phenotypically syncytium inducing (SI); exclusively uses CXCR4;
      and replicates well in CCR5 -/- primary T cells. The recently discovered
      coreceptors BOB and Bonzo are not used. Although early and persistent SI variants
      have been described in longitudinal studies, this is the first demonstration of
      exclusive and persistent CXCR4 usage. With the caveat that the earliest viruses
      available from this subject were from approximately 4 years following primary
      infection, these data suggest that HIV-1 infection can be mediated and
      persistently maintained by viruses which exclusively utilize CXCR4. The lack of
      evolution toward the available minor coreceptors in this subject underscores the
      dominant biological roles of the major coreceptors CCR5 and CXCR4. This and two
      similar subjects (R. Biti, R. Ffrench, J. Young, B. Bennetts, G. Stewart, and T.
      Liang, Nat. Med. 3:252-253, 1997; I. Theodoreu, L. Meyer, M. Magierowska, C.
      Katlama, and C. Rouzioux, Lancet 349:1219-1220, 1997) showed relatively rapid
      CD4+ T-cell declines despite average or low initial viral RNA load. Since viruses
      which use CXCR4 exclusively cannot infect macrophages, these data have
      implications for the relative infection of the T-cell compartment versus the
      macrophage compartment in vivo and for the development of CCR5-based
      therapeutics.

PMID- 9621068
TI  - The native form and maturation process of hepatitis C virus core protein.
AB  - The maturation and subcellular localization of hepatitis C virus (HCV) core
      protein were investigated with both a vaccinia virus expression system and CHO
      cell lines stably transformed with HCV cDNA. Two HCV core proteins, with
      molecular sizes of 21 kDa (p21) and 23 kDa (p23), were identified. The C-terminal
      end of p23 is amino acid 191 of the HCV polyprotein, and p21 is produced as a
      result of processing between amino acids 174 and 191. The subcellular
      localization of the HCV core protein was examined by confocal laser scanning
      microscopy. Although HCV core protein resided predominantly in the cytoplasm, it
      was also found in the nucleus and had the same molecular size as p21 in both
      locations, as determined by subcellular fractionation. The HCV core proteins had
      different immunoreactivities to a panel of monoclonal antibodies. Antibody 5E3
      stained core protein in both the cytoplasm and the nucleus, C7-50 stained core
      protein only in the cytoplasm, and 499S stained core protein only in the nucleus.
      These results clearly indicate that the p23 form of HCV core protein is processed
      to p21 in the cytoplasm and that the core protein in the nucleus has a higher
      order structure different from that of p21 in the cytoplasm. HCV core protein in
      sera of patients with HCV infection was analyzed in order to determine the
      molecular size of genuinely processed HCV core protein. HCV core protein in sera
      was found to have exactly the same molecular weight as the p21 protein. These
      results suggest that p21 core protein is a component of native viral particles.

PMID- 9621069
TI  - UL27.5 is a novel gamma2 gene antisense to the herpes simplex virus 1 gene
      encoding glycoprotein B.
AB  - An antibody made against the herpes simplex virus 1 US5 gene predicted to encode
      glycoprotein J was found to react strongly with two proteins, one with an
      apparent Mr of 23,000 and mapping in the S component and one with a herpes
      simplex virus protein with an apparent Mr of 43,000. The antibody also reacted
      with herpes simplex virus type 2 proteins forming several bands with apparent Mrs
      ranging from 43,000 to 50,000. Mapping studies based on intertypic recombinants,
      analyses of deletion mutants, and ultimately, reaction of the antibody with a
      chimeric protein expressed by in-frame fusion of the glutathione S-transferase
      gene to an open reading frame antisense to the gene encoding glycoprotein B led
      to the definitive identification of the new open reading frame, designated
      UL27.5. Sequence analyses indicate the conservation of a short amino acid
      sequence common to US5 and UL27.5. The coding sequence of the herpes simplex
      virus UL27.5 open reading frame is strongly homologous to the sequence encoding
      the carboxyl terminus of the herpes simplex virus 2 UL27.5 sequence. However,
      both open reading frames could encode proteins predicted to be significantly
      larger than the mature UL27.5 proteins accumulating in the infected cells,
      indicating that these are either processed posttranslationally or synthesized
      from alternate, nonmethionine-initiating codons. The UL27.5 gene expression is
      blocked by phosphonoacetate, indicating that it is a gamma2 gene. The product
      accumulated predominantly in the cytoplasm. UL27.5 is the third open reading
      frame found to map totally antisense to another gene and suggests that additional
      genes mapping antisense to known genes may exist.

PMID- 9621070
TI  - Structure and phylogenetic analysis of an endogenous retrovirus inserted into the
      human growth factor gene pleiotrophin.
AB  - A human endogenous retrovirus-like element (HERV), flanked by long terminal
      repeats of 502 and 495 nucleotides is inserted into the human pleiotrophin (PTN)
      gene upstream of the open reading frame. Based on its Glu-tRNA primer binding
      site specificity and the location within the PTN gene, we named this element HERV
      E.PTN. HERV-E.PTN appears to be a recombined viral element based on its high
      homology (70 to 86%) in distinct areas to members of two distantly related HERV
      type C families, HERV-E and retrovirus-like element I (RTVL-I). Furthermore, its
      pseudogene region is organized from 5' to 3' into gag-, pol-, env-, pol-, env
      similar sequences. Interestingly, full-length and partial HERV-E.PTN-homologous
      sequences were found in the human X chromosome, the human hereditary
      haemochromatosis region, and the BRCA1 pseudogene. Finally, Southern analyses
      indicate that the HERV-E.PTN element is present in the PTN gene of humans,
      chimpanzees, and gorillas but not of rhesus monkeys, suggesting that genomic
      insertion occurred after the separation of monkeys and apes about 25 million
      years ago.

PMID- 9621071
TI  - Mouse mammary tumor virus superantigen expression in B cells is regulated by a
      central enhancer within the pol gene.
AB  - Expression of mouse mammary tumor virus (MMTV)-encoded superantigens in B
      lymphocytes is required for viral transmission and pathogenesis. The mechanism of
      superantigen expression from the viral sag gene in B cells is largely unknown,
      due to problems with detection and quantification of these low-abundance
      proteins. We have established a sensitive superantigen-luciferase reporter assay
      to study the expression and regulation of the MMTV sag gene in B-cell lymphomas.
      The regulatory elements for retroviral gene expression are generally located in
      the 5' long terminal repeat (LTR) of the provirus. However, we found that neither
      promoters nor enhancers in the MMTV 5' LTR play a significant role in
      superantigen expression in these cells. Instead, the essential regulatory regions
      are located in the pol and env genes of MMTV. We report here that maximal sag
      expression in B-cell lines depends on an enhancer within the viral pol gene which
      can be localized to a minimal 183-bp region. Regulation of sag gene expression
      differs between B-cell lymphomas and pro-B cells, where an enhancer within the
      viral LTRs is involved. Thus, MMTV sag expression during B-cell development is
      achieved through the use of two separate enhancer elements.

PMID- 9621072
TI  - T-Cell response to woodchuck hepatitis virus (WHV) antigens during acute self
      limited WHV infection and convalescence and after viral challenge.
AB  - The infection of woodchucks with woodchuck hepatitis virus (WHV) provides an
      experimental model to study early immune responses during hepadnavirus infection
      that cannot be tested in patients. The T-cell response of experimentally WHV
      infected woodchucks to WHsAg, rWHcAg, and WHcAg peptides was monitored by
      observing 5-bromo-2'-deoxyuridine and [2-3H]adenine incorporation. The first T
      cell responses were directed against WHsAg 3 weeks after infection; these were
      followed by responses to rWHcAg including the immunodominant T-cell epitope of
      WHcAg (amino acids 97 to 110). Maximal proliferative responses were detected when
      the animals seroconvered to anti-WHs and anti-WHc (week 6). A decrease in the T
      cell response to viral antigens coincided with clearance of viral DNA. Polyclonal
      rWHcAg-specific T-cell lines were established 6, 12, 18, and 24 weeks
      postinfection, and their responses to WHcAg peptides were assessed. Five to seven
      peptides including the immunodominant epitope were recognized throughout the
      observation period (6 months). At 12 months after infection, T-cell responses to
      antigens and peptides were not detected. Reactivation of T-cell responses to
      viral antigens and peptides occurred within 7 days after challenge of animals
      with WHV. These results demonstrate that a fast and vigorous T-cell response to
      WHsAg, rWHcAg, and amino acids 97 to 110 of the WHcAg occurs within 3 weeks after
      WHV infection. The peak of this response was associated with viral clearance and
      may be crucial for recovery from infection. One year after infection, no
      proliferation of T cells in response to antigens was observed; however, the WHV
      specific T-cell response was reactivated after challenge of woodchucks with WHV
      and may be responsible for protection against WHV reinfection.

PMID- 9621073
TI  - Structural and antigenic analysis of a truncated form of the herpes simplex virus
      glycoprotein gH-gL complex.
AB  - The herpes simplex virus (HSV) gH-gL complex is essential for virus infectivity
      and is a major antigen for the host immune system. The association of gH with gL
      is required for correct folding, cell surface trafficking, and membrane
      presentation of the complex. Previously, a mammalian cell line was constructed
      which produces a secreted form of gHt-gL complex lacking the transmembrane and
      cytoplasmic tail regions of gH. gHt-gL retains a conformation similar to that of
      its full-length counterpart in HSV-infected cells. Here, we examined the
      structural and antigenic properties of gHt-gL. We first determined its
      stoichiometry and carbohydrate composition. We found that the complex consists of
      one molecule each of gH and gL. The N-linked carbohydrate (N-CHO) site on gL and
      most of the N-CHO sites on gH are utilized, and both proteins also contain O
      linked carbohydrate and sialic acid. These results suggest that the complex is
      processed to the mature form via the Golgi network prior to secretion. To
      determine the antigenically active sites of gH and gL, we mapped the epitopes of
      a panel of gH and gL monoclonal antibodies (MAbs), using a series of gH and gL C
      terminal truncation variant proteins produced in transiently transfected
      mammalian cells. Sixteen gH MAbs (including H6 and 37S) reacted with the N
      terminal portion of gH between amino acids 19 and 276. One of the gH MAbs, H12,
      reacted with the middle portion of gH (residues 476 to 678). Nine gL MAbs
      (including 8H4 and VIII 62) reacted with continuous epitopes within the C
      terminal portion of gL, and this region was further mapped within amino acids 168
      to 178 with overlapping synthetic peptides. Finally, plasmids expressing the gH
      and gL truncations were employed in cotransfection assays to define the minimal
      regions of both gH and gL required for complex formation and secretion. The first
      323 amino acids of gH and the first 161 amino acids of gL can form a stable
      secreted hetero-oligomer with gL and gH792, respectively, while gH323-gL168 is
      the smallest secreted hetero-oligomer. The first 648 amino acids of gH are
      required for reactivity with MAbs LP11 and 53S, indicating that a complex of
      gH648-gL oligomerizes into the correct conformation. The data suggest that both
      antigenic activity and oligomeric structure require the amino-terminal portions
      of gH and gL.

PMID- 9621074
TI  - Human herpesvirus 6 open reading frame U12 encodes a functional beta-chemokine
      receptor.
AB  - Human herpesvirus 6 (HHV- 6), which belongs to the betaherpesvirus subfamily and
      infects mainly T cells in vitro, causes acute and latent infections. HHV- 6
      contains two genes (U12 and U51) that encode putative homologs of cellular G
      protein-coupled receptors (GCR), while three other betaherpesviruses, human
      cytomegalovirus, murine cytomegalovirus, and human herpesvirus 7, have three,
      one, and two GCR-homologous genes, respectively. The U12 gene is expressed late
      in infection from a spliced mRNA. The U12 gene was cloned, and the protein was
      expressed in cells and analyzed for its biological characteristics. U12
      functionally encoded a calcium-mobilizing receptor for beta-chemokines such as
      regulated upon activation, normal T expressed and secreted (RANTES), macrophage
      inflammatory proteins 1alpha and 1beta (MIP-1alpha and MIP-1beta) and monocyte
      chemoattractant protein 1 but not for the alpha-chemokine interleukin-8,
      suggesting that the chemokine selectivity of the U12 product was distinct from
      that of the known mammalian chemokine receptors. These findings suggested that
      the product of U12 may play an important role in the pathogenesis of HHV- 6
      through transmembrane signaling by binding with beta-chemokines.

PMID- 9621075
TI  - The orphan seven-transmembrane receptor apj supports the entry of primary T-cell
      line-tropic and dualtropic human immunodeficiency virus type 1.
AB  - Human immunodeficiency virus type 1 (HIV-1) enters target cells by sequential
      binding to CD4 and specific seven-transmembrane-segment (7TMS) coreceptors.
      Viruses use the chemokine receptor CCR5 as a coreceptor in the early,
      asymptomatic stages of HIV-1 infection but can adapt to the use of other
      receptors such as CXCR4 and CCR3 as the infection proceeds. Here we identify one
      such coreceptor, Apj, which supported the efficient entry of several primary T
      cell-line tropic (T-tropic) and dualtropic HIV-1 isolates and the simian
      immunodeficiency virus SIVmac316. Another 7TMS protein, CCR9, supported the less
      efficient entry of one primary T-tropic isolate. mRNAs for both receptors were
      present in phytohemagglutinin- and interleukin-2-activated peripheral blood
      mononuclear cells. Apj and CCR9 share with other coreceptors for HIV-1 and SIV an
      N-terminal region rich in aromatic and acidic residues. These results highlight
      properties common to 7TMS proteins that can function as HIV-1 coreceptors, and
      they may contribute to an understanding of viral evolution in infected
      individuals.

PMID- 9621076
TI  - Heparan sulfate proteoglycan binding by herpes simplex virus type 1 glycoproteins
      B and C, which differ in their contributions to virus attachment, penetration,
      and cell-to-cell spread.
AB  - Herpes simplex virus type 1 (HSV-1) mutants defective for envelope glycoprotein C
      (gC) and gB are highly impaired in the ability to attach to cell surface heparan
      sulfate (HS) moieties of proteoglycans, the initial virus receptor. Here we
      report studies aimed at defining the HS binding element of HSV-1 (strain KOS) gB
      and determining whether this structure is functionally independent of gB's role
      in extracellular virus penetration or intercellular virus spread. A mutant form
      of gB deleted for a putative HS binding lysine-rich (pK) sequence (residues 68 to
      76) was transiently expressed in Vero cells and shown to be processed normally,
      leading to exposure on the cell surface. Solubilized gBpK- also had substantially
      lower affinity for heparin-acrylic beads than did wild-type gB, confirming that
      the HS binding domain had been inactivated. The gBpK- gene was used to rescue a
      KOS gB null mutant virus to produce the replication-competent mutant KgBpK-.
      Compared with wild-type virus, KgBpK- showed reduced binding to mouse L cells
      (ca. 20%), while a gC null mutant virus in which the gC coding sequence was
      replaced by the lacZ gene (KCZ) was substantially more impaired (ca. 65%-reduced
      binding), indicating that the contribution of gC to HS binding was greater than
      that of gB. The effect of combining both mutations into a single virus (KgBpK-gC
      ) was additive (ca. 80%-reduced binding to HS) and displayed a binding activity
      similar to that observed for KOS virus attachment to sog9 cells, a
      glycosaminoglycan-deficient L-cell line. Cell-adsorbed individual and double HS
      mutant viruses exhibited a lower rate of virus entry following attachment,
      suggesting that HS binding plays a role in the process of virus penetration.
      Moreover, the KgBpK- mutant virus produced small plaques on Vero cells in the
      presence of neutralizing antibody where plaque formation depended on cell-to-cell
      virus spread. These studies permitted the following conclusions: (i) the pK
      sequence is not essential for gB processing or function in virus infection, (ii)
      the lysine-rich sequence of gB is responsible for HS binding, and (iii) binding
      to HS is cooperatively linked to the process of efficient virus entry and lateral
      spread but is not absolutely required for virus infectivity.

PMID- 9621077
TI  - Human immunodeficiency virus tat modulates the Flk-1/KDR receptor, mitogen
      activated protein kinases, and components of focal adhesion in Kaposi's sarcoma
      cells.
AB  - Kaposi's sarcoma (KS) spindle cell growth and spread have been reported to be
      modulated by various cytokines as well as the human immunodeficiency virus (HIV)
      gene product Tat. Recently, HIV-1 Tat has been shown to act like a cytokine and
      bind to the Flk-1/KDR receptor for the vascular endothelial growth factor A (VEGF
      A), which is expressed by KS cells. We have characterized signal transduction
      pathways stimulated by HIV-1 Tat upon its binding to surface receptors on KS
      cells. We observed that stimulation in KS 38 spindle cells resulted in tyrosine
      phosphorylation and activation of the Flk-1/KDR receptor. We also report that HIV
      1 Tat treatment enhanced the phosphorylation and association of proteins found in
      focal adhesions, such as the related adhesion focal tyrosine kinase RAFTK,
      paxillin, and p130(cas). Further characterization revealed the activation of
      mitogen-activated protein kinase, c-Jun amino-terminal kinase (JNK), and Src
      kinase. HIV-1 Tat contains a basic domain which can interact with growth factor
      tyrosine kinase receptors and a classical RGD sequence which may bind to and
      activate the surface integrin receptors for fibronectin and vitronectin. We
      observed that stimulation of KS cells with basic as well as RGD sequence
      containing Tat peptides resulted in enhanced phosphorylation of RAFTK and
      activation of MAP kinase. These studies reveal that Tat stimulation activates a
      number of signal transduction pathways that are associated with cell growth and
      migration.

PMID- 9621078
TI  - Role of E4 in eliciting CD4 T-cell and B-cell responses to adenovirus vectors
      delivered to murine and nonhuman primate lungs.
AB  - Adenovirus vectors delivered to lung are being considered in the treatment of
      cystic fibrosis (CF). Vectors from which E1 has been deleted elicit T- and B-cell
      responses which confound their use in the treatment of chronic diseases such as
      CF. In this study, we directly compare the biology of an adenovirus vector from
      which E1 has been deleted to that of one from which E1 and E4 have been deleted,
      following intratracheal instillation into mouse and nonhuman primate lung.
      Evaluation of the E1 deletion vector in C57BL/6 mice demonstrated dose-dependent
      activation of both CD4 T cells (i.e., TH1 and TH2 subsets) and neutralizing
      antibodies to viral capsid proteins. Deletion of E4 and E1 had little impact on
      the CD4 T-cell proliferative response and cytolytic activity of CD8 T cells
      against target cells expressing viral antigens. Analysis of T-cell subsets from
      mice exposed to the vector from which E1 and E4 had been deleted demonstrated
      preservation of TH1 responses with markedly diminished TH2 responses compared to
      the vector with the deletion of E1. This effect was associated with reduced TH2
      dependent immunoglobulin isotypes and markedly diminished neutralizing
      antibodies. Similar results were obtained in nonhuman primates. These studies
      indicate that the vector genotype can modify B-cell responses by differential
      activation of TH1 subsets. Diminished humoral immunity, as was observed with the
      E1 and E4 deletion vectors in lung, is indeed desired in applications of gene
      therapy where readministration of the vector is necessary.

PMID- 9621079
TI  - Novel Gag-Pol frameshift site in human immunodeficiency virus type 1 variants
      resistant to protease inhibitors.
AB  - Human immunodeficiency virus type 1 (HIV-1) variants resistant to protease
      inhibitors have been shown to contain a mutation in the p1/p6 Gag precursor
      cleavage site. At the messenger RNA level, this mutation generates a U UUU UUU
      sequence that is reminiscent of the U UUU UUA sequence required for ribosomal
      frameshifting and Gag-Pol synthesis. To test whether the p1/p6 cleavage site
      mutation was generating a novel frameshift site, HIV sequences were inserted in
      translation vectors containing a chloramphenicol acetyltransferase (CAT) reporter
      gene requiring -1 frameshifting for expression. All sequences containing the
      original HIV frameshift site supported the synthesis of CAT but expression was
      increased 3- to 11-fold in the presence of the mutant p1/p6 sequence. When the
      original frameshift site was abolished by mutation, expression remained unchanged
      when using constructs containing the mutant p1/p6 sequence, whereas it was
      decreased 2- to 4.5-fold when using wild-type p1/p6 constructs. Similarly, when
      introduced into HIV molecular clones, the p1/p6 mutant sequence supported Gag-Pol
      synthesis and protease activity in the absence of the original frameshift site,
      indicating that this sequence could also promote ribosomal frameshifting in virus
      expressing cells.

PMID- 9621080
TI  - Human papillomavirus type 11 recombinant L1 capsomeres induce virus-neutralizing
      antibodies.
AB  - The human papillomavirus type 11 (HPV-11) L1 major capsid protein can be
      trypsinized to generate recombinant capsomeres that retain HPV genotype
      restricted capsid antigenicity (M. Li, T. P. Cripe, P. A. Estes, M. K. Lyon, R.
      C. Rose, and R. L. Garcea, J. Virol. 71:2988-2995, 1997). In the present study,
      HPV-11 virion-neutralizing monoclonal antibodies H11.F1 and H11.H3, previously
      characterized as recognizing two distinct HPV-11 capsid-neutralizing antigenic
      domains (S. W. Ludmerer, D. Benincasa, and G. E. Mark III, J. Virol. 70:4791
      4794, 1996), were each found to be highly immunoreactive with trypsin-generated
      capsomeres in an enzyme-linked immunosorbent assay (ELISA). Capsomeres were used
      to generate high-titer polyclonal immune sera that demonstrated HPV genotype
      restricted reactivity by ELISA. The capsomere antisera were then tested in an in
      vitro infectivity assay and found to neutralize HPV-11 virions. In this assay,
      HPV-11 capsomere polyclonal antisera exhibited neutralization titers (10(-5) to
      10(-6)) comparable to those obtained with a virion-neutralizing antiserum raised
      previously against intact HPV-11 VLPs (R. C. Rose, R. C. Reichman, and W. Bonnez,
      J. Gen. Virol. 75:2075-2079, 1994). These results indicate that highly
      immunogenic, genotype-restricted HPV capsid-neutralizing antigenic domains are
      contained entirely within capsomeres. Thus, capsomeres may be viable vaccine
      candidates for the prevention of HPV disease.

PMID- 9621081
TI  - Costimulatory pathways in lymphocyte proliferation induced by the simian
      immunodeficiency virus SIVsmmPBj14.
AB  - The PBj14 isolate of the simian immunodeficiency virus SIVsmmPBj14 is unique
      among primate lentiviruses in its ability to induce lymphocyte proliferation and
      acutely lethal disease. The studies reported here show that viral induction of T
      cell proliferation requires accessory cells, such as primary monocytes or Raji B
      lymphoma cells, as well as the presence of a putative immunoreceptor tyrosine
      based activation motif within the viral Nef protein. Addition of CTLA4
      immunoglobulin fusion protein or anti-B7 antibodies to virally infected T cells
      led to substantial, but not complete, inhibition of monocyte-costimulated T-cell
      proliferation-suggesting that both CD28/B7-dependent and non-CD28-dependent
      pathways may contribute to the costimulation of virally induced
      lymphoproliferation. Finally, cyclosporin A, a specific inhibitor of the calcium
      calmodulin-regulated phosphatase activity of calcineurin, which influences
      activation of the transcription factor nuclear factor of activated T cells, was
      shown to block virally mediated T-cell proliferation. Taken together, these
      findings suggest that the effect of SIVsmmPBj14 on T-cell activation may be
      functionally analogous, at least in part, to the effect of engagement of the T
      cell receptor.

PMID- 9621082
TI  - Enhanced gene transfer with fusogenic liposomes containing vesicular stomatitis
      virus G glycoprotein.
AB  - Exposure of Lipofectin-DNA complexes to the partially purified G glycoprotein of
      the vesicular stomatitis virus envelope (VSV-G) results in loss of serum-mediated
      inhibition and in enhanced efficiency of gene transfer. Sucrose density gradient
      sedimentation analysis indicated that the VSV-G associates physically with the
      DNA-lipid complex to produce a VSV-G liposome. The ability to incorporate
      surrogate viral or cellular envelope components such as VSV-G into liposomes may
      allow more-efficient and possibly targeted gene delivery by lipofection, both in
      vitro and in vivo.

PMID- 9621083
TI  - A human endogenous retrovirus suppresses translation of an associated fusion
      transcript, PLA2L.
AB  - Human endogenous retroviruses (HERVs) are repetitive, noninfectious chromosomal
      elements degenerated from exogenous retroviruses. The HERV-H family is composed
      of approximately 1,000 elements which are dispersed throughout the human genome.
      We have shown previously that an HERV-H element splices into a downstream locus,
      termed PLA2L, which has a large open reading frame (ORF) containing two domains
      with phospholipase A2 homology. Over half of the putative 5' untranslated region
      (5' UTR) of the resulting fusion transcript is derived from HERV-H long-terminal
      repeat and internal sequences. As 5' UTRs are known to modulate translation
      initiation, we tested for possible effects upon gene expression at the
      translation level due to the 5' fusion with HERV-H sequences. No PLA2L protein
      was detected in teratocarcinoma cell lines in which PLA2L mRNA is abundantly
      expressed. In addition, despite a high level of transcription, no protein
      synthesis was detected when the full-length PLA2L cDNA was expressed in COS
      cells. Upon removal of the 5'-terminal HERV-H sequences, PLA2L protein was seen
      in transfectants. The 5' UTR contains both small ORFs and a strong predicted RNA
      secondary structure, both of which have been shown to contribute to translation
      suppression. The HERV-H sequences, combined with a unique PLA2L 5' UTR sequence,
      form a predicted RNA stem-loop that has a stability greater than that proposed to
      negatively affect translation. Interestingly, this stem-loop is abolished when
      the HERV-H sequences are removed. We hypothesize that the PLA2L 5' HERV-H
      sequences function as an abnormally long and complex 5' UTR, resulting in
      suppression of translation in both teratocarcinoma cell lines and full-length
      cDNA transfectants. This is the first known example of a endogenous retrovirus
      integration affecting expression of a heterologous human gene at the
      translational level.

PMID- 9621084
TI  - Role of individual T-cell epitopes of Theiler's virus in the pathogenesis of
      demyelination correlates with the ability to induce a Th1 response.
AB  - Intracerebral inoculation of susceptible strains of mice with Theiler's murine
      encephalomyelitis virus (TMEV) results in immune-mediated demyelination. Three
      major T-cell epitopes have previously been identified within the VP1 (VP1233
      250), VP2 (VP274-86), and VP3 (VP324-37) capsid proteins in virus-infected SJL/J
      mice. These epitopes appear to account for the majority ( approximately 90%) of
      major histocompatibility complex class II-restricted T-cell responses to TMEV.
      Interestingly, the effect of immunization with synthetic peptides bearing the
      predominant T-cell epitopes on the course of TMEV-induced demyelination indicates
      that T cells reactive to the VP1 and VP2 epitopes, but not VP3, accelerate the
      pathogenesis of demyelination. The predominant pathogenic role of the T cells is
      verified by similar immunization with the fusion proteins containing the entire
      individual capsid proteins. The order of appearance and level of T cells specific
      for the individual epitopes during the course of demyelination are similar to
      each other. However, cytokine profiles of T cells from virus-infected mice
      indicate that T cells specific for the VP1 (and perhaps the VP2) epitope are Th1,
      whereas T cells reactive to VP3 are primarily Th2. These results suggest that Th1
      type cells specific for VP1 and VP2 are involved in the pathogenesis of viral
      demyelination induced by TMEV. Thus, a predominance of Th1-inducing viral
      epitopes is likely critical for the pathogenesis of demyelination.

PMID- 9621086
TI  - Up to 100-fold increase of apparent gene expression in the presence of Epstein
      Barr virus oriP sequences and EBNA1: implications of the nuclear import of
      plasmids.
AB  - A 100-fold increase in luciferase activity was observed in 293 cells, stably
      expressing Epstein-Barr nuclear antigen 1 (EBNA1; 293-EBNA1 cells), that had been
      transiently transfected with plasmids carrying Epstein-Barr virus (EBV) oriP
      sequences. This increase was observed in comparison to reporter gene activity
      obtained after transfection with a plasmid carrying no oriP sequences. The
      luciferase gene on these plasmids was under the control of either the
      cytomegalovirus immediate-early 1 gene enhancer-promoter (CMV IE1) or the Rous
      sarcoma virus promoter. The increase of reporter gene activity was not due to
      plasmid replication, since a similar enhancement was observed in the presence of
      aphidicolin, an inhibitor of replicative DNA synthesis, or after deletion of the
      dyad symmetry (DS) element within oriP. Luciferase production was not increased
      in the presence of only the DS element. Microinjection of plasmids carrying the
      CMV IE1 promoter-driven luciferase gene with or without oriP sequences into the
      nuclei of 293-EBNA1 cells resulted in a 17-fold increase in luciferase activity.
      Cytoplasmic injection of these plasmids led to an enhancement of luciferase
      activity of up to 100-fold. This difference in the factor of activation after
      nuclear or cytoplasmic injection could be ascribed to increased transport of
      plasmids carrying oriP from the cytoplasm to the nucleus in the presence of
      EBNA1. These data suggest the possibility of substantially increasing the
      apparent expression of a gene under the control of a strong constitutive promoter
      in the presence of oriP sequences and EBNA1. This improvement in expression is
      due to intranuclear enhancement of gene expression. oriP-specific transport of
      plasmid DNA from the cytoplasm of 293-EBNA1 cells to the nucleus seems to
      contribute to the observed effect.

PMID- 9621085
TI  - Woodchuck hepatitis virus enhancer I and enhancer II are both involved in N-myc2
      activation in woodchuck liver tumors.
AB  - Direct activation of the N-myc2 oncogene by insertion of woodchuck hepatitis
      virus (WHV) DNA is a major oncogenic step in woodchuck hepatocarcinogenesis. We
      previously reported that WHV enhancer II (We2), which controls expression of the
      core/pregenome RNA, can also activate the N-myc2 promoter in hepatoma cell lines.
      To better define the integrated WHV regulatory sequences responsible for N-myc2
      promoter activation in woodchuck liver tumors, we analyzed the structure and
      enhancer activity of a single viral integrant found at the win locus in tumor
      2260T1 and mapping approximately 175 kb 3' of N-myc2. This viral insert was made
      of 11 concatemerized WHV fragments, 5 of which overlapped with We2 sequences and
      1 with WHV sequence homologous to that of hepatitis B virus enhancer I (We1). In
      transient transfection assays in hepatoma-derived cells, the We2 activator was
      found to be fully effective only when inserted in close proximity to the N-myc2
      promoter whereas the We1 element by itself was apparently devoid of activity. In
      contrast, the 2260T1 viral insert exhibited a potent enhancer capacity that
      depended both on multimerized We2 and on We1 sequences. In a survey of different
      woodchuck hepatomas, both elements were commonly found within integrated viral
      sequences involved in long-range N-myc2 activation.

PMID- 9621087
TI  - Papillomavirus assembly requires trimerization of the major capsid protein by
      disulfides between two highly conserved cysteines.
AB  - We have used viruslike particles (VLPs) of human papillomaviruses to study the
      structure and assembly of the viral capsid. We demonstrate that mutation of
      either of two highly conserved cysteines of the major capsid protein L1 to serine
      completely prevents the assembly of VLPs but not of capsomers, whereas mutation
      of all other cysteines leaves VLP assembly unaffected. These two cysteines form
      intercapsomeric disulfides yielding an L1 trimer. Trimerization comprises about
      half of the L1 molecules in VLPs but all L1 molecules in complete virions. We
      suggest that trimerization of L1 is indispensable for the stabilization of
      intercapsomeric contacts in papillomavirus capsids.

PMID- 9621088
TI  - A minimal avian retroviral packaging sequence has a complex structure.
AB  - We have defined a 160-nucleotide region, Mpsi, from the 5' leader region of the
      Rous sarcoma virus genome that is sufficient to direct the packaging of a
      heterologous RNA. Mpsi contains the putative O3 stem structure that has
      previously been shown, and that has been confirmed in this study, to be important
      for the efficient packaging of avian leukosis-sarcoma virus RNA. Analyses of
      several O3 stem mutants revealed that other regions within Mpsi can interfere
      with the proper folding of altered sequences which are predicted to form a wild
      type O3 stem.

PMID- 9621089
TI  - Site-specific integration of adeno-associated virus into an episome with the
      target locus via a deletion-substitution mechanism.
AB  - Five site-specific adeno-associated virus integrants generated in a model system
      with an Epstein-Barr virus- based shuttle vector have been characterized. The
      results suggest a deletion-substitution mechanism of recombination.

PMID- 9621090
TI  - The NS5A/NS5 proteins of viruses from three genera of the family flaviviridae are
      phosphorylated by associated serine/threonine kinases.
AB  - Phosphorylation of the expressed NS5A protein of hepatitis C virus (HCV), a
      member of the Hepacivirus genus of the family Flaviviridae, has been demonstrated
      in mammalian cells and in a cell-free assay by an associated kinase activity. In
      this report, phosphorylation is also shown for the NS5A and NS5 proteins,
      respectively, of bovine viral diarrhea virus (BVDV) and yellow fever virus (YF),
      members of the other two established genera in this family. Phosphorylation of
      BVDV NS5A and YF NS5 was observed in infected cells, transient expression
      experiments, and a cell-free assay similar to the one developed for HCV NS5A.
      Phosphoamino acid analyses indicated that all three proteins were phosphorylated
      by serine/threonine kinases. Similarities in the properties of BVDV NS5A, YF NS5,
      and HCV NS5A phosphorylation in vitro further suggested that closely related
      kinases or the same kinase may phosphorylate these viral proteins. Conservation
      of this trait among three quite distantly related viruses representing three
      separate genera suggests that phosphorylation of the NS5A/NS5 proteins or their
      association with cellular kinases may play an important role in the flavivirus
      life cycle.

PMID- 9621092
TI  - CXCR4 and CCR5 genetic polymorphisms in long-term nonprogressive human
      immunodeficiency virus infection: lack of association with mutations other than
      CCR5-Delta32.
AB  - Polymorphisms in the coding sequences of CCR5 and CXCR4 were studied in a group
      of human immunodeficiency virus (HIV)-infected long-term nonprogressors. Two
      different point mutations were found in the CXCR4 coding sequence. One of these
      CXCR4 mutations was silent, and each was unique to two nonprogressors. The well
      described 32-bp deletion within the CCR5 coding sequence (CCR5-Delta32) was found
      in 4 of 13 nonprogressors, and 12 different point mutations were found scattered
      over the CCR5 coding sequence from 8 nonprogressors. Most of the mutations
      created either silent or conservative changes in the predicted amino acid
      sequence: only one of these mutations was found in more than a single
      nonprogressor. All nonsilent mutations were tested in an HIV envelope-dependent
      fusion assay, and all functioned comparably to wild-type controls. Polymorphisms
      in the CXCR4 and CCR5 coding sequences other than CCR5-Delta32 do not appear to
      play a dominant mechanistic role in nonprogression among HIV-infected
      individuals.

PMID- 9621091
TI  - The protein tyrosine kinase p56lck is required for triggering NF-kappaB
      activation upon interaction of human immunodeficiency virus type 1 envelope
      glycoprotein gp120 with cell surface CD4.
AB  - We have previously shown that NF-kappaB nuclear translocation can be observed
      upon human immunodeficiency virus type 1 (HIV-1) binding to cells expressing the
      wild-type CD4 molecule, but not in cells expressing a truncated form of CD4 that
      lacks the cytoplasmic domain (M. Benkirane, K.-T. Jeang, and C. Devaux, EMBO J.
      13:5559-5569, 1994). This result indicated that the signaling cascade which
      controls HIV-1-induced NF-kappaB activation requires the integrity of the CD4
      cytoplasmic tail and suggested the involvement of a second protein that binds to
      this portion of the molecule. Here we investigate the putative role of p56(lck)
      as a possible cellular intermediate in this signal transduction pathway. Using
      human cervical carcinoma HeLa cells stably expressing CD4, p56(lck), or both
      molecules, we provide direct evidence that expression of CD4 and p56(lck) is
      required for HIV-1-induced NF-kappaB translocation. Moreover, the fact that HIV-1
      stimulation did not induce nuclear translocation of NF-kappaB in cells expressing
      a mutant form of CD4 at position 420 (C420A) and the wild-type p56(lck) indicates
      the requirement for a functional CD4-p56(lck) complex.

PMID- 9621093
TI  - Polymorphisms of the hepatitis A virus cellular receptor 1 in African green
      monkey kidney cells result in antigenic variants that do not react with
      protective monoclonal antibody 190/4.
AB  - Monoclonal antibody (MAb) 190/4 blocks binding of hepatitis A virus (HAV) to the
      HAV cellular receptor 1 (havcr-1) and protects African green monkey kidney (AGMK)
      clone GL37 cells (GL37 cells) against HAV infection. BS-C-1 and CV-1 cells, two
      widely used AGMK cell lines, did not react with MAb 190/4 but expressed havcr-1,
      as judged by Western blot analysis. The cDNA coding for havcr-1 was amplified
      from BS-C-1 and CV-1 total cellular RNA by reverse transcription-PCR. Alignment
      of the amino acid sequences inferred from the cDNA nucleotide sequences showed
      that BS-C-1 and CV-1 havcr-1 differed from GL37 havcr-1 by having two
      substitutions in the Cys-rich region, N48H and K108Q, and 10 to 11 additional
      substitutions plus the insertion of 18 to 22 amino acids in the mucin-like
      region. Studies with chimeras of GL37 havcr-1 and BS-C-1 havcr-1 showed that the
      K108Q substitution was responsible for the lack of reaction of MAb 190/4 with BS
      C-1 and CV-1 cells. Binding studies indicated that HAV bound to dog cell
      transfectants expressing the BS-C-1 havcr-1 as well as the GL37/BS-C-1 havcr-1
      chimeras. These results indicate that antigenic variants of havcr-1 are expressed
      in AGMK cells and that binding of HAV to these havcr-1 variants tolerates changes
      in protective epitope 190/4.

PMID- 9621094
TI  - Human herpesvirus 8 in the prostate glands of men with Kaposi's sarcoma.
AB  - The epidemiology of human immunodeficiency virus (HIV)-associated Kaposi's
      sarcoma (KS) resembles that of a sexually transmitted pathogen. However, human
      herpesvirus 8 (HHV-8), the proposed cause of KS, is found in semen only
      infrequently and at low titers. To determine whether HHV-8 was present in the
      urogenital tract, transrectal ultrasound-guided prostate biopsies were obtained
      from six men with KS (five with concurrent HIV infection) and four without KS
      (three with concurrent HIV) and assayed for HHV-8 by PCR. Nine of the 10 men were
      seropositive for HHV-8. Five of nine HHV-8-seropositive men had HHV-8 DNA
      detected in prostate tissue by solution-based PCR. All five currently had KS or
      had it previously. In two subjects, prostate tissue was the only identified
      source of HHV-8. In situ PCR on serial sections of prostate indicated that HHV-8
      infection was localized to discrete areas of the prostate. When detected, HHV-8
      DNA was present in the nuclei of >90% of the glandular epithelial cells. In situ
      hybridization for HHV-8 mRNA revealed that between 1 and 5% of cells harboring
      HHV-8 DNA expressed viral transcripts associated with HHV-8 replication (T1.1
      transcript), while >90% expressed gene products associated with viral latency
      (T0.7 transcript). Intermittent replication of HHV-8 in the prostate and
      subsequent shedding of virus in semen may be crucial factors for determining
      whether HHV-8 can be transmitted through sexual activity.

PMID- 9621095
TI  - Cloning and functional analysis of Kaposi's sarcoma-associated herpesvirus DNA
      polymerase and its processivity factor.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV), or human herpesvirus 8, is a
      newly identified virus with tumorigenic potential. Here, we cloned and expressed
      the DNA polymerase (Pol-8) of KSHV and its processivity factor (PF-8). Pol-8
      bound specifically to PF-8 in vitro. Moreover, the DNA synthesis activity of Pol
      8 was shown in vitro to be strongly dependent on PF-8. Addition of PF-8 to Pol-8
      allowed efficient synthesis of fully extended DNA products corresponding to the
      full-length M13 template (7,249 nucleotides), whereas Pol-8 alone could
      incorporate only several nucleotides. The specificity of PF-8 and Pol-8 for each
      other was demonstrated by their inability to be functionally replaced by the DNA
      polymerases and processivity factors of herpes simplex virus 1 and human
      herpesvirus 6.

PMID- 9621096
TI  - The agnogene of the human polyomavirus BK is expressed.
AB  - Primate polyomavirus genomes all contain an open reading frame at the 5' end of
      the late coding region called the agnogene. A simian virus 40 agnoprotein with
      unknown functions has previously been demonstrated. We now show that a BK virus
      agnoprotein appears in the perinuclear area and cytoplasm late in the infectious
      cycle. It is phosphorylated in vivo and coimmunoprecipitates with a subset of
      host cell proteins.

PMID- 9621097
TI  - Effects of substituting granulin or a granulin-polyhedrin chimera for polyhedrin
      on virion occlusion and polyhedral morphology in Autographa californica
      multinucleocapsid nuclear polyhedrosis virus.
AB  - Substitution of granulin from the Trichoplusia ni granulosis virus (TnGV) for
      polyhedrin of the Autographa californica multinucleocapsid nuclear polyhedrosis
      virus (AcMNPV) yielded a few very large (2 to 5 micron) cuboidal inclusions in
      the cytoplasm and nucleus of infected cells. These polyhedra lacked the beveled
      edges characteristic of wild-type AcMNPV polyhedra, contained fractures, and
      occluded few virions. Placing a nuclear localization signal (KRKK) in granulin
      directed more granulin to the nucleus and resulted in more structurally uniform
      cuboidal inclusions in which no virions were observed. A granulin-polyhedrin
      chimera produced tetrahedral occlusions with more virions than granulin
      inclusions but many fewer than wild-type polyhedra. Despite the unusual structure
      of the granulin and granulin-polyhedrin inclusions, they interacted with AcMNPV
      p10 fibrillar structures and electron-dense spacers that are precursors of the
      polyhedral calyx. The change in inclusion shape obtained with the granulin
      polyhedrin chimera demonstrates that the primary amino acid sequence affects
      occlusion body shape, but the large cuboidal inclusions formed by granulin
      indicate that the amino acid sequence is not the only determinant. The failure of
      granulin or the granulin-polyhedrin chimera to properly occlude AcMNPV virions
      suggests that specific interactions occur between polyhedrin and other viral
      proteins which facilitate normal virion occlusion and occlusion body assembly and
      shape in baculoviruses.

PMID- 9621098
TI  - The domain structure of ICAM-1 and the kinetics of binding to rhinovirus.
AB  - Fragments of intercellular adhesion molecule 1 (ICAM- 1) containing only the two
      most N terminal of its five immunoglobulin SF domains bind to rhinovirus 3 with
      the same affinity and kinetics as a fragment with the entire extracellular
      domain. The fully active two-domain fragments contain 5 or 14 more residues than
      a previously described fragment that is only partially active. Comparison of X
      ray crystal structures show differences at the bottom of domain 2. Four different
      glycoforms of ICAM- 1 bind with identical kinetics.

PMID- 9621099
TI  - A single amino acid change in turnip crinkle virus movement protein p8 affects
      RNA binding and virulence on Arabidopsis thaliana.
AB  - Comparison of the symptoms caused by turnip crinkle virus strain M (TCV-M) and
      TCV-B infection of a resistant Arabidopsis thaliana line termed Di-17
      demonstrates that TCV-B has a greater ability to spread in planta. This ability
      is due to a single amino acid change in the viral movement protein p8 and
      inversely correlates with p8 RNA binding affinity.

PMID- 9621100
TI  - Characterization of the molecular mechanism of defective interfering RNA-mediated
      symptom attenuation in tombusvirus-infected plants.
AB  - Different tombusviruses were able to support the replication of either homologous
      or heterologous defective interfering (DI) RNAs, and those infected plants
      usually developed typical attenuated symptoms. However, in some helper virus-DI
      RNA combinations the inoculated plants were necrotized, although they contained a
      high level of DI RNA, suggesting that the accumulation of DI RNA and the
      resulting suppression of genomic RNA replication were not directly responsible
      for the symptom attenuation. Moreover, the 19-kDa protein product of ORF 5, which
      is known to play a crucial role in necrotic symptom development, accumulated at
      the same level in the infected plants in the presence of protective homologous DI
      RNA and in the presence of nonprotective heterologous DI RNA. It was also
      demonstrated, by chimeric helper viruses, that the ability of heterologous DI RNA
      to protect the virus-infected plants against systemic necrosis is determined by
      the 5'-proximal region of the helper virus genome. The results presented suggest
      that DI RNA-mediated protection did not operate via the specific inhibition of 19
      kDa protein expression but, more likely, DI RNAs in protective DI-helper virus
      combinations specifically interacted with viral products, preventing the
      induction of necrotic symptoms.

PMID- 9621101
TI  - Inhibition of human immunodeficiency virus type 1 virion entry by dominant
      negative Hck.
AB  - To study the role of Src family tyrosine kinases in infection with human
      immunodeficiency virus type 1 (HIV-1), we constructed an Hck mutant, HckN, that
      hinders signaling from wild-type Hck. HIV-1 produced in HckN-expressing cells was
      significantly less infectious to HeLa-CD4-LTR-beta-gal (MAGI) cells than HIV-1
      produced in mock-transfected cells. The inhibitory effect of HckN was compensated
      for by the expression of vesicular stomatitis virus G protein. Finally, we found
      that the HIV-1 produced in the HckN-expressing cells entered into the cells less
      efficiently than did the control HIV-1. These results suggest that the Src family
      tyrosine kinases regulate entry of HIV-1 into target cells.

PMID- 9621102
TI  - Coreceptor usage of human immunodeficiency virus type 2 primary isolates and
      biological clones is broad and does not correlate with their syncytium-inducing
      capacities.
AB  - Entry of human immunodeficiency virus type 1 (HIV-1) into target cells is
      mediated by binding of the surface envelope glycoprotein to the CD4 molecule.
      Interaction of the resulting CD4-glycoprotein complex with alpha- or beta
      chemokine receptors, depending on the biological phenotype of the virus, then
      initiates the fusion process. Here, we show that primary HIV-2 isolates and
      biological clones, in contrast to those of HIV-1, may use a broad range of
      coreceptors, including CCR-1, CCR-3, CCR-5, and CXCR-4. The syncytium-inducing
      capacity of these viruses did not correlate with the ability to infect via CXCR-4
      or any other coreceptor. One cell-free passage of the intermediate isolates in
      mitogen-stimulated, CD8+ cell-depleted peripheral blood mononuclear cells
      resulted in the outgrowth of variants with CCR-5 only, whereas the coreceptor
      usage of late and early isolates did not change. Since HIV-2 is less pathogenic
      in vivo than HIV-1, these data suggest that HIV pathogenicity in vivo is not
      directly related to the spectrum of coreceptors used in in vitro systems.

PMID- 9621103
TI  - Activation of human T-cell leukemia virus type 1 tax gene expression in
      chronically infected T cells.
AB  - Expression of human T-cell leukemia virus type 1 (HTLV-1) is regulated both by
      the HTLV-1 Tax transactivator and by cellular transcriptional factors binding to
      the viral long terminal repeat (LTR), suggesting that cellular signals may play a
      role in regulating viral expression. Treatment of cells chronically infected with
      HTLV-1, which express low levels of HTLV-1 RNAs and Tax protein, with phorbol
      esters (i.e., phorbol12-myristate 13- acetate [PMA]), phytohemagglutinin (PHA),
      sodium butyrate, or combinations of cytokines resulted in induction of HTLV- 1
      gene expression. PMA or PHA treatment following cotransfection of HTLV-1 Tax
      expression plasmids resulted in synergistic activation of HTLV-1 LTR-directed
      gene expression, apparently involving tyrosine ki- nase- mediated pathways. These
      results suggest that cellular activation stimuli may cooperate with HTLV-1 Tax to
      enhance expression of integrated HTLV-1 genomes and thus may play a role in the
      pathogenesis of HTLV-1 disease.

PMID- 9621104
TI  - Evolution of hypervariable region 1 of hepatitis C virus in primary infection.
AB  - The hypervariable region 1 (HVR-1) of the putative envelope encoding E2 region of
      hepatitis C virus (HCV) RNA was analyzed in sequential samples from three
      patients with acute type C hepatitis infected from different sources to address
      (i) the dynamics of intrahost HCV variability during the primary infection and
      (ii) the role of host selective pressure in driving viral genetic evolution. HVR
      1 sequences from 20 clones per each point in time were analyzed after
      amplification, cloning, and purification of plasmid DNA from single colonies of
      transformed cells. The intrasample evolutionary analysis (nonsynonymous mutations
      per nonsynonymous site [Ka], synonymous mutations per synonymous site [Ks], Ka/Ks
      ratio, and genetic distances [gd]) documented low gd in early samples (ranging
      from 2. 11 to 7.79%) and a further decrease after seroconversion (from 0 to
      4.80%), suggesting that primary HCV infection is an oligoclonal event, and found
      different levels and dynamics of host pressure in the three cases. The
      intersample analysis (pairwise comparisons of intrapatient sequences; rKa, rKs,
      rKa/rKs ratio, and gd) confirmed the individual features of HCV genetic evolution
      in the three subjects and pointed to the relative contribution of either neutral
      evolution or selective forces in driving viral variability, documenting that
      adaptation of HCV for persistence in vivo follows different routes, probably
      representing the molecular counterpart of the viral fitness for individual
      environments.

PMID- 9621105
TI  - Glycosphingolipid expression in pig aorta: identification of possible target
      antigens for human natural antibodies.
AB  - Total non-acid glycosphingolipids were isolated from the aortas of more than 80
      pigs. The glycolipids were separated by HPLC, analysed by thin-layer
      chromatography, and tested for reactivity with monoclonal anti-blood group
      antibodies. The fractions were structurally characterized by NMR spectroscopy and
      mass spectrometry. Reactivity with both anti-blood group A and H antibodies was
      seen. The major glycosphingolipid constituents were globotri- and
      globotetraosylceramides and blood group H pentaglycosylceramides based on type 1
      and type 2 core saccharide chains. Globopentaosylceramides, blood group H
      hexaglycosylceramides based on type 4 chain, and blood group A
      hexaglycosylceramides based on type 1 core chain were also present. Two
      structures, that may be important targets for human antibodies initiating
      hyperacute rejection following pig to human xenotransplantation, were present as
      minor constituents compared to the blood group components. These were
      Galalpha1,3neolactotetraosylceramide and a Galalpha1, 3Lexstructure. A Leb/Y
      hexaglycosylceramide was also present.

PMID- 9621106
TI  - Core alpha1,3-fucose is a key part of the epitope recognized by antibodies
      reacting against plant N-linked oligosaccharides and is present in a wide variety
      of plant extracts.
AB  - Carbohydrates have been suggested to account for some IgE cross-reactions between
      various plant, insect, and mollusk extracts, while some IgG antibodies have been
      successfully raised against plant glycoproteins. A rat monoclonal antibody raised
      against elderberry abscission tissue (YZ1/2.23) and rabbit polyclonal antiserum
      against horseradish peroxidase were screened for reactivity in enzyme-linked
      immunosorbent assay against a range of plant glycoproteins and extracts as well
      as neoglycoproteins, bee venom phospholipase, and several animal glycoproteins.
      Of the oligosaccharides tested, Man3XylFucGlcNAc2(MMXF3) derived from horseradish
      peroxidase was the most potent inhibitor of the reactivity of both YZ1/2.23 and
      anti-horseradish peroxidase to native horseradish peroxidase glycoprotein. The
      reactivity of YZ1/2. 23 and anti-horseradish peroxidase against Sophora japonica
      lectin was most inhibited by a neoglycoconjugate of bromelain glycopeptide cross
      linked to bovine serum albumin, while the defucosylated form of this conjugate
      was inactive as an inhibitor. A wide range of plant extracts was found to react
      against YZ1/2.23 and anti-horseradish peroxidase, with particularly high
      reactivities recorded for grass pollen and nut extracts. All these reactivities
      were inhibitable with the bromelain glycopeptide/bovine serum albumin conjugate.
      Bee venom phospholipase and whole bee venom reacted weakly with YZ1/2.23 but more
      strongly with anti-horseradish peroxidase in a manner inhibitable with the
      bromelain glycopeptide/bovine serum albumin conjugate, while hemocyanin from
      Helix pomatia reacted poorly with YZ1/2.23 but did react with anti-horseradish
      peroxidase. It is concluded that the alpha1, 3-fucose residue linked to the
      chitobiose core of plant glycoproteins is the most important residue in the
      epitope recognized by the two antibodies studied, but that the polyclonal anti
      horseradish peroxidase antiserum also contains antibody populations that
      recognize the xylose linked to the core mannose of many plant and gastropod N
      linked oligosaccharides.

PMID- 9621107
TI  - Partially glucose-capped oligosaccharides are found on the hemoglobins of the
      deep-sea tube worm Riftia pachyptila.
AB  - We report here the structural determination of N-linked oligosaccharides found on
      extracellular hemoglobins of the hydrothermal vent tube worm Riftia pachyptila.
      Structures were elucidated by a combination of electrospray ionization tandem
      mass spectrometry, matrix-assisted laser desorption/ionization mass spectrometry,
      normal-phase high performance liquid chromatography, and exoglycosidase
      digestion. The sugar chains were found to consist mainly of high-mannose-type
      glycans with some structures partially capped by one or two terminal glucose
      residues. The present study represents the first report of the occurrence of
      glucose capping of N-linked carbohydrates in a secreted glycoprotein of a
      metazoan. Previously, glucose capping has only been described for a membrane
      bound surface glycoprotein from the unicellular parasite Leishmania mexicana
      amazonensis.

PMID- 9621108
TI  - Newly found 2-N-acetyl-2,6-dideoxy-beta-glucopyranose containing methyl glucose
      polysaccharides in M.bovis BCG: revised structure of the mycobacterial methyl
      glucose lipopolysaccharides.
AB  - The specific mycobacterial methyl polysaccharides 3- O -methyl mannose
      polysaccharide (MMP) and the 6- O -methyl glucose lipopolysaccharides (MGLPs)
      were shown to modulate the fatty acid biosynthesis by the mycobacterial fatty
      acid synthetase I (FAS I). This activity is attributed to their fatty acid
      complexing properties allowing the release of the neo synthesized fatty acyl
      chain from the enzyme and probably their transport in the cell. To elucidate, at
      a molecular level, the mechanism of this unusual kind of polysaccharide-lipid
      biological interaction, we first analyzed, by mass spectrometry and proton
      nuclear magnetic resonance (1H NMR) spectroscopy, the structure of the
      polysaccharidic backbone (MGPs) of the MGLPs from Mycobacterium bovis BCG. This
      work reveals that this strain produces a new kind of MGP containing an unusual
      monosaccharide never described in the mycobacterial genus: a 2- N -acetyl-2,6
      dideoxy-beta-glucopyranosyl. In addition,1H NMR data afforded evidence for the
      revision of three glycosidic linkages described previously. These modifications
      affect mainly the reducing end tetrasaccharide and have great consequences on the
      previously proposed molecular model of the MGP.

PMID- 9621109
TI  - High resolution and high sensitivity methods for oligosaccharide mapping and
      characterization by normal phase high performance liquid chromatography following
      derivatization with highly fluorescent anthranilic acid.
AB  - Facile labeling of oligosaccharides (acidic and neutral) in a nonselective manner
      was achieved with highly fluorescent anthranilic acid (AA, 2-aminobenzoic acid)
      (more than twice the intensity of 2-aminobenzamide, AB) for specific detection at
      very high sensitivity. Quantitative labeling in acetate-borate buffered methanol
      (approximately pH 5.0) at 80 degreesC for 60 min resulted in negligible or no
      desialylation of the oligosaccharides. A high resolution high performance liquid
      chromatographic method was developed for quantitative oligosaccharide mapping on
      a polymeric-NH2bonded (Astec) column operating under normal phase and anion
      exchange (NP-HPAEC) conditions. For isolation of oligosaccharides from the map by
      simple evaporation, the chromatographic conditions developed use volatile acetic
      acid-triethylamine buffer (approximately pH 4.0) systems. The mapping and
      characterization technology was developed using well characterized standard
      glycoproteins. The fluorescent oligosaccharide maps were similar to the maps
      obtained by the high pH anion-exchange chromatography with pulsed amperometric
      detection (HPAEC-PAD), except that the fluorescent maps contained more defined
      peaks. In the map, the oligosaccharides separated into groups based on charge,
      size, linkage, and overall structure in a manner similar to HPAEC-PAD with
      contribution of -COOH function from the label, anthranilic acid. However,
      selectivity of the column for sialic acid linkages was different. A second
      dimension normal phase HPLC (NP-HPLC) method was developed on an amide column
      (TSK Gel amide-80) for separation of the AA labeled neutral complex type and
      isomeric structures of high mannose type oligosaccharides. The oligosaccharides
      labeled with AA are compatible with biochemical and biophysical techniques, and
      use of matrix assisted laser desorption mass spectrometry for rapid determination
      of oligosaccharide mass map of glycoproteins is demonstrated. High resolution of
      NP-HPAEC and NP-HPLC methods combined with mass spectrometry (MALDI-TOF) can
      provide an effective technology for analyzing a wide repertoire of
      oligosaccharide structures and for determining the action of both transferases
      and glycosidases.

PMID- 9621110
TI  - Delineation of the epitope recognized by an antibody specific for N
      glycolylneuraminic acid-containing gangliosides.
AB  - P3 is a mouse monoclonal antibody (mAb) that binds to several NeuGc-containing
      gangliosides. It also reacts with antigens expressed in human breast tumors
      (Vazquez et al. (1995) Hybridoma , 14, 551-556). In this work, the binding
      specificity of P3 has been characterized in more detail using a panel of
      glycolipids that included several disialylated gangliosides and several chemical
      derivatives of NeuGc-GM3. The carboxyl group and the nitrogen function of sialic
      acid were found to play important roles in the antibody binding, whereas the
      glycerol tail appears to be nonrelevant. Molecular modeling was used to analyze
      the binding data, including the finding that P3 selectively recognizes the
      internal NeuGc in GD3. For this purpose, conformational studies of GD3 were
      performed using molecular dynamics. It was concluded that sialic acid binds the
      P3 antibody through its upper face (the one on which the carboxyl group is
      exposed) and the C4-C5 side of the sugar ring, whereas none or very little
      contact between the galactose residue and the protein is evident. Conformational
      analysis of GD3 revealed that, despite the large flexibility of the
      NeuGcalpha8NeuGc linkage, the P3 binding epitope on the external sialic acid is
      not well exposed for any of the possible conformations this linkage can adopt,
      whereas the internal sialic acid presents the epitope in a proper way for several
      of these conformations. As a final result, a coherent picture of the epitope that
      fits the wide binding data was obtained.

PMID- 9621111
TI  - Inhibition of L- and P-selectin by a rationally synthesized novel core 2-like
      branched structure containing GalNAc-Lewisx and Neu5Acalpha2-3Galbeta1-3GalNAc
      sequences.
AB  - The selectins interact in important normal and pathological situations with
      certain sialylated, fucosylated glycoconjugate ligands containing sialyl
      Lewisx(Neu5Acalpha2-3Galbeta1-4(Fucalpha1-3)GlcN Ac). Much effort has gone into
      the synthesis of sialylated and sulfated Lewisxanalogs as competitive ligands for
      the selectins. Since the natural selectin ligands GlyCAM-1 and PSGL-1 carry
      sialyl Lewisxas part of a branched Core 2 O-linked structure, we recently
      synthesized Galbeta1-4(Fucalpha1-3)GlcNAcbeta1-6(SE-3Galbeta1++ +
      3)GalNAc1alphaOMe and found it to be a moderately superior ligand for L and P
      selectin (Koenig et al. , Glycobiology 7, 79-93, 1997). Other studies have shown
      that sulfate esters can replace sialic acid in some selectin ligands (Yeun et al.
      , Biochemistry, 31, 9126-9131, 1992; Imai et al. , Nature, 361, 555, 1993). Based
      upon these observations, we hypothesized that Neu5Acalpha2-3Galbeta1-3GalNAc
      might have the capability of interacting with L- and P-selectin. To examine this
      hypothesis, we synthesized Galbeta1-4(Fucalpha1-3)GlcNAcbeta1-6(Neu5Acalpha2++ +
      3Galbeta1-3)-GalNAc alpha1-OB, which was found to be 2- to 3-fold better than
      sialyl Lexfor P and L selectin, respectively. We also report the synthesis of an
      unusual structure GalNAcbeta1-4(Fucalpha1- 3)GlcNAcbeta1-OMe (GalNAc-Lewisx-O
      methyl glycoside), which also proved to be a better inhibitor of L- and P
      selectin than sialyl Lewisx-OMe. Combining this with our knowledge of Core 2
      branched structures, we have synthesized a molecule that is 5- to 6-fold better
      at inhibiting L- and P-selectin than sialyl Lewisx-OMe, By contrast to unbranched
      structures, substitution of a sulfate ester group for a sialic acid residue in
      such a molecule resulted in a considerable loss of inhibition ability. Thus, the
      combination of a sialic acid residue on the primary (beta1-3) arm, and a modified
      Lexunit on the branched (beta1-6) arm on an O-linked Core 2 structure generated a
      monovalent synthetic oliogosaccharide inhibitor superior to SLexfor both L- and P
      selectin.

PMID- 9621112
TI  - Ion-spray mass spectrometry for identification of the nonreducing terminal sugar
      of glycosaminoglycan.
AB  - Various oligosaccharides from hyaluronic acid, which have glucuronic acid or N-
      acetylglucosamine at the nonreducing terminal, were prepared by digestion with a
      combination of testicular hyaluronidase and beta-glucuronidase. These oligo
      saccharides were analyzed by negative-mode ion-spray mass spectrometry (MS) with
      an atmospheric pressure ion source. Introduction of collisionally activated
      dissociation tandem mass spectrometry (CAD-MS/MS) produced ions derived from
      cleavage of the glycosidic bonds, allowing the structure to be analyzed. The CAD
      MS/MS spectrum showed an intense and characteristic fragment ion at m/z 193 for
      oligosaccharides having glucuronic acid at the nonreducing terminal. On the other
      hand, this ion was not observed in the spectra of oligosaccharides having N-
      acetylglucosamine at the nonreducing terminal. Therefore, the fragmentation
      pattern revealed by CAD-MS/MS provides useful information for distinguishing
      glucuronic acid and N- acetylglucosamine at the nonreducing terminal of
      oligosaccharides derived from hyaluronic acid and other glycosaminoglycans. This
      ion-spray CAD-MS/MS technique was also applied successfully to the
      characterization of glycosaminoglycans reconstructed by glycotechnology.

PMID- 9621113
TI  - Processing of viral envelope glycoprotein by the endomannosidase pathway:
      evaluation of host cell specificity.
AB  - Endo-alpha-D-mannosidase is an enzyme involved in N-linked oligosaccharide
      processing which through its capacity to cleave the internal linkage between the
      glucose-substituted mannose and the remainder of the polymannose carbohydrate
      unit can provide an alternate pathway for achieving deglucosylation and thereby
      make possible the continued formation of complex oligosaccharides during a
      glucosidase blockade. In view of the important role which has been attributed to
      glucose on nascent glycoproteins as a regulator of a number of biological events,
      we chose to further define the in vivo action of endomannosidase by focusing on
      the well characterized VSV envelope glycoprotein (G protein) which can be formed
      by the large array of cell lines susceptible to infection by this pathogen.
      Through an assessment of the extent to which the G protein was converted to an
      endo-beta-N-acetylglucosaminidase (endo H)-resistant form during a
      castanospermine imposed glucosidase blockade, we found that utilization of the
      endomannosidase-mediated deglucosylation route was clearly host cell specific,
      ranging from greater than 90% in HepG2 and PtK1 cells to complete absence in CHO,
      MDCK, and MDBK cells, with intermediate values in BHK, BW5147.3, LLC-PK1, BRL,
      and NRK cell lines. In some of the latter group the electrophoretic pattern after
      endo H treatment suggested that only one of the two N-linked oligosaccharides of
      the G protein was processed by endomannosidase. In the presence of the specific
      endomannosidase inhibitor, Glcalpha1-->3(1-deoxy)mannojirimycin, the conversion
      of the G protein into an endo H-resistant form was completely arrested. While the
      lack of G protein processing by CHO cells was consistent with the absence of in
      vitro measured endomannosidase activity in this cell line, the failure of MDBK
      and MDCK cells to convert the G protein into an endo H-resistant form was
      surprising since these cell lines have substantial levels of the enzyme.
      Similarly, we observed that influenza virus hemagglutinin was not processed in
      castanospermine-treated MDCK cells. Our findings suggest that studies which rely
      on glucosidase inhibition to explore the function of glucose in controlling such
      critical biological phenomena as intracellular movement or quality control should
      be carried out in cell lines in which the glycoprotein under study is not a
      substrate for endomannosidase action.

PMID- 9621114
TI  - beta1,6 N-acetylglucosaminyltransferase (core 2 GlcNAc-T) expression in normal
      rat tissues and different cell lines: evidence for complex mechanisms of
      regulation.
AB  - The distribution of the Golgi enzyme beta1, 6-N-acetylglucosaminyltransferase
      (core 2 GlcNAc-T for short) has been investigated in several tissue and cell
      systems by combining the potentials of a polyclonal antibody and a novel,
      sensitive fluorescent enzyme assay. In normal rat tissues, levels of the protein
      were found to vary and as a general trend did not correlate with enzyme
      activities. Additionally, we observed tissue-specific core 2 GlcNAc-T forms of
      various size: 75 kDa (liver), 70 kDa (spleen), 60 kDA (heart), and 50 kDa (heart
      and lung). These forms might arise from differential protein modifications;
      alternatively, the smaller form may be a product of proteolytic cleavage, given
      the presence of a catalytically inactive 50 kDa species in rat serum. Chinese
      hamster ovary (CHO), MDAY-D2, PSA-5E, and PYS-2 cell lines consistently displayed
      a 70 kDa enzyme. When induced to retrodifferentiate in the presence of butyrate +
      cholera toxin, CHO cells exhibited a 21-fold increase in enzyme activity, while
      protein levels remained constant. A similar trend was observed in the embryonal
      endoderm cell lines PSA-5E and PYS-2, where an approximately 100-fold difference
      in core 2 GlcNAc-T activity was found notwithstanding unchanged amounts of the
      protein and identical mRNA levels, as evidenced by RT-PCR. In contrast, levels of
      core 2 GlcNAc-T activity in MDAY-D2 cells correlated well with protein
      expression. Taken together, these observations demonstrate that core 2 GlcNAc-T
      expression may be subjected to multiple mechanisms of regulation and suggest that
      in at least some instances (i.e., PSA-5E and PYS-2 cells) expression may be
      regulated exclusively via posttranslational mechanism(s) of control.

PMID- 9621115
TI  - N-Linked glycosylation of a baculovirus-expressed recombinant glycoprotein in
      insect larvae and tissue culture cells.
AB  - The potential of insect cell cultures and larvae infected with recombinant
      baculoviruses to produce authentic recombinant glycoproteins cloned from
      mammalian sources was investigated. A comparison was made of the N-linked glycans
      attached to secreted alkaline phosphatase (SEAP) produced in four species of
      insect larvae and their derived cell lines plus one additional insect cell line
      and larvae of one additional species. These data survey N-linked oligosaccharides
      produced in four families and six genera of the order Lepidoptera. Recombinant
      SEAP expressed by recombinant isolates of Autographa californica and Bombyx mori
      nucleopolyhedroviruses was purified from cell culture medium, larval hemolymph or
      larval homogenates by phosphate affinity chromatography. The N-linked
      oligosaccharides were released with PNGase-F, labeled with 8-aminonaphthalene-1-3
      6-trisulfonic acid, fractionated by polyacrylamide gel electrophoresis, and
      analyzed by fluorescence imaging. The oligosaccharide structures were confirmed
      with exoglycosidase digestions. Recombinant SEAP produced in cell lines of
      Lymantria dispar (IPLB-LdEIta), Heliothis virescens (IPLB-HvT1), and Bombyx mori
      (BmN) and larvae of Spodoptera frugiperda, Trichoplusia ni , H.virescens , B.mori
      , and Danaus plexippus contained oligosaccharides that were structurally
      identical to the 10 oligosaccharides attached to SEAP produced in T.ni cell
      lines. The oligosaccharide structures were all mannose-terminated. Structures
      containing two or three mannose residues, with and without core fucosylation,
      constituted more than 75% of the oligosaccharides from the cell culture and
      larval samples.

PMID- 9621116
TI  - [Role of CAAT/enhancer binding protein in IL-6 regulation of angiotensinogen gene
      expression].
AB  - OBJECTIVE: Angiotensinogen is the only known precursor of vasoactive angiotensin
      II and also one of the acute phase proteins. This study was intended to
      understand the regulation of angiotensinogen gene expression induced by IL-6.
      METHODS: Northern hybridization, electrophoretic mobility shift assay and
      transient transfections were conducted. RESULTS: Northern hybridization showed
      increase of angiotensinogen mRNA treated by IL-6 in Hep3B cells. Electrophoretic
      mobility shift assay further indicated the HAG IL-6RE homologous to IL-6
      responsive element at -568 site of the angiotensinogen promoter binds
      C/EBP(CAAT/Enhancer Binding Protein). Consistent with this binding studies were
      the transient transfections of the expression vector in which 6 copies of HAG-IL
      6RE linked to TK core promoter and fused to CAT reporter gene, revealing that
      C/EBPalpha was a transactivator under IL-6-induced condition. CONCLUSION: These
      observations suggest that C/EBP plays regulatory role in IL-6-induced
      angiotensinogen gene expression.

PMID- 9621117
TI  - [A molecular variant of angiotensinogen gene is associated with myocardial
      infarction in Chinese].
AB  - OBJECTIVE: A molecular variant of the angiotensinogen(AGT) gene with threonine
      instead of methionine at position 235(i.e.,with M235T polymor- phism) has been
      shown to be associated with essential hypertension, preeclampsia, coronary
      atherosclerosis, coronary heart disease(CHD), myocardial infarction(MI) in
      Caucasians and in Japanese. The purpose of the present study was to assess
      whether the M235T polymorphism was associated with MI in a Chinese population.
      METHODS: M235T polymorphism in exon 2 of AGT gene was determined by polymerase
      chain reaction(PCR) and restriction endonuclease analysis in a study of 57
      patients with MI and 76 non-CHD individuals as control. RESULTS: The frequencies
      of T235 allele(0.82) and 235TT genotype (0.70) in the MI group were higher than
      those in the control subjects(0.63 and 0.42 respectively, P=0.013 and P<0.025).
      AGT gene 235TT genotype was at significantly increased risk of MI(odds ratio
      3.65, P=0.016) in analysis adjusted for several main CHD risk factors.
      CONCLUSION: There is a significant association between AGT gene 235TT genotype
      and MI, this genotype might be an independent risk for MI in Chinese population.

PMID- 9621118
TI  - [The relationship between angiotensin-converting enzyme gene polymorphism and
      brain infarction in Chinese hypertensives].
AB  - OBJECTIVE: To identify the insertion/deletion(I/D) polymorphism of angiotensin
      converting enzyme(ACE) gene in Chinese hypertensives complicated with brain
      infarction. METHODS: ACE genotyping with polymerase chain reaction(PCR) was
      performed in 62 unrelated healthy controls, 55 hypertensives without cardio
      cerebrovascular diseases and 44 hypertensives complicated with brain infarction
      (all controls had no hypertension family history, while the cases had
      hypertension family history). RESULTS: No significant differences could be
      detected between ACE gene I/D polymorphism and hypertension. However,the
      frequencies of DD genotype and deletion allele among hypertensives complicated
      with brain infarction (29.6% vs 56.8%) were higher than those among healthy
      controls (12.9% vs 38.7%, P<0.05 and P<0.01) and those among hypertensive without
      cardio-cerebrovascular diseases(12. 8% vs 40%, P<0.05 and P<0.02). CONCLUSION: A
      deletion polymorphism of ACE gene is probably an important hereditary factor of
      brain infarction's morbidity in Chinese hypertensives. The detection of ACE
      genotypes in hypertensives would improve the early diagnosis of brain infarction.

PMID- 9621119
TI  - [Distinct Rb gene point mutations in families showing low penetrance of
      hereditary retinoblastoma].
AB  - OBJECTIVE: To investigate the possible cause and molecular mechanism of low
      penetrance in hereditary retinoblastoma kindred. METHODS: The DNAs from tumor or
      blood of affected and unaffected individuals in hereditary retinoblastoma
      families showing low penetrance were screened by SSCP analysis and further
      characterized by direct DNA sequencing. RESULTS: Eight from fifteen families
      showing low penetrance retinoblastoma were identified to have distinct Rb gene
      point mutations including Arg661-Trp661 in five families, aberrant splicing in
      two families and a G-T mutation at ATF binding site of Rb gene promoter in one
      family. CONCLUSION: The distribution of cases with low penetrance of
      retinoblastoma is not completely random. The low penetrance in the families
      described here was associated with several distinct Rb gene point mutations which
      did not result in complete disruption of the gene product,and the reduced
      penetrance of retinoblastoma is probably the result of a residual function of
      these alleles in retinoblastoma precursor cells.

PMID- 9621120
TI  - [Construction of a competitor for bcr-abl cDNA by recombinant PCR].
AB  - OBJECTIVE: Competitive PCR is a powerful method for quantification of mRNA. This
      study sought to construct an internal standard which can be used as a competitor
      for bcr-abl fusion cDNA. METHODS: Using recombinant PCR for site-directed
      mutagenesis. RESULTS A 240bp mimic of a 276bp fragment in b3a2 type of bcr-abl
      cDNA was obtained. The difference in mimic,which was verified by DNA sequencing,
      was a 55bp deletion of the target sequence and a 19bp insertion of exogenous
      unrelated sequence with a XbaI restriction site. In it, except for the inner
      36bp, the mimic contained the same sequence and shared the same primer
      recognition sites as the target b3a2 cDNA(276bp) or as the target b2a2
      cDNA(201bp). The obtained recombinant vector, named pGEM-mimic, can be used as a
      common competitor for either b3a2 or b2a2 type of bcr-abl cDNA. CONCLUSION: This
      provided a simple and reliable method for constructing an internal standard used
      in competitive PCR.

PMID- 9621121
TI  - [Genetic polymorphism at D20S161 locus in Chinese populations].
AB  - OBJECTIVE: To understand the genetic relationship between different populations
      in China and to obtain the preliminary data on the genetic poly- morphisms of
      D20S161 in seven populations in China. METHODS: EDTA-blood specimens were
      collected from 753 healthy unrelated individuals in seven Chinese populations,
      including Chengdu(Han), Guangzhou(Han),Jilin(Han),Lasa (Tibetans),Dali(Bai),
      Nanning(Zhuang) and Hailaer(Menggu),respectively. DNA was extracted with Chelex
      method. The DNA samples were amplified by PCR technique, and the PAGE horizontal
      electrophoresis was used for typing the PCR products. RESULTS: Seven alleles at
      D20S161 locus were observed in six populations,while six alleles at D20S161 were
      observed in one population in Dali(Bai). The numbers of genotypes observed were
      25, 19,21,19,16,20 and 22 for Chengdu(Han), Guangzhou(Han), Jilin(Han),
      Lasa(Tibetans), Dali(Bai), Nanning(Zhuang)and Hailaer(Menggu), respectively. The
      allele frequencies were D20S161*16:0.0220-0.0657, D20S161*17:0.1429
      0.2947,D20S161*18: 0.3237-0.4835. D20S161*19:0. 0909-0.1850,D20S161*20:0.1263
      0.1786,D20S161* 21: 0.0421-0.1010, D20S161*22:0-0.0250.A total of 26 genotypes
      were observed in 753 individuals. The heterozygosity was between 65.31% 80.41%
      for the seven populations. The results of test for Hardy-Weinberg equilibrium
      showed that the genotype distributions observed were correspondent with the
      expected. CONCLUSION: There are seven alleles in Chinese populations, of which
      D20S161*18 is most frequently observed. No significant difference in the
      distribution of allele frequencies at D20S161 (X2=57.9342,P>0.01) was noted among
      the seven Chinese populations. D20S161 may be a very useful genetic marker for
      both paternity test and personal identification of casework in forensic medicine
      and for the purpose of population genetics.

PMID- 9621122
TI  - [G6PD gene mutations in Guangxi, China].
AB  - OBJECTIVE: Fifty-six G6PD-deficient male individuals of the Guangxi origin were
      investigated at the molecular level to understand the basis of G6PD deficiency.
      METHODS: PCR amplified the exons 2,5,6,7,8, 10,11,12 and 13 of the G6PD gene
      respectively, combined with ASO dot blot hybridization and restriction enzymes
      digestion methods to screen 10 common Chinese G6PD mutations. RESULTS: Six
      mutations were detected, namely cDNA1376(G-->T)(25.0%), cDNA1388(G-->A)(16.1%),
      cDNA95(A-->G)(19.8%), cDNA592 (C-->T)(7.1%), cDNA1024(C-->T)(1.8%) and cDNA392(G-
      >T) (1.8%). The unknown mutations accounted for 28.6%. cDNA1311(C-->T),cDNA1360(C
      ->T),cDNA835(A-->T), cDNA493(A-->G) and cDNA487(G-->A) were not discovered among
      the cases. CONCLUSION: The findings may provide some useful informations for
      physician scientists to get insight into the pathogenesis of G6PD deficiency so
      as to improve clinical diagnosis, prevention and cure of G6PD deficiency. The
      results may be of significance in anthropology and geneties as well.

PMID- 9621123
TI  - [Studies of microsatellite instability in Chinese gastric cancer tissues].
AB  - OBJECTIVE: To identify the microsatellite instability(MSI) rates in Chinese
      gastric cancer samples. METHODS: 29 microsatellite markers were selected to
      examine 42 paired gastric cancer tissues for MSI on all chromosomes except Y.
      RESULTS: The total frequency of MSI in all 42 gastric cancers was 33.9% with
      higher rates at loci of D3S1577, D3S1067,D8S279,D9S257, D1S248, D7S520 and
      D2S147,and the highest rate at D3S1577 and D3S1067(51.35%). MSI varied with
      different pathological types. The frequencies of MSI were signi- ficantly higher
      in poorly differentiated tumors and signet cell types, compared with well
      differentiated tumors(P=0.0026 and 0.0013 by chi-square test),and no difference
      was noted between poorly differentiated and signet cell types. CONCLUSION: MSI
      may play an important role in Chinese gastric cancer, particularly the poorly
      differentiated adenocarcinomas. The data presented here further support the
      previous hypothesis that pathologically distinct subtypes of gastric cancer
      undergo different genetic pathways during tumorigenesis.

PMID- 9621124
TI  - [A technique of constructing human chromosomal band-specific probe pools using
      degenerate oligonucleotide primer].
AB  - OBJECTIVE: To establish a rapid and efficient technique of constructing human
      chromosomal band specific probe pools and their libraries. METHODS: A modified
      method of combining chromosome microdissection with degenerate oligonucleotide
      primed PCR(DOP-PCR) was used. 3p23-p26, 3q21-q22 and 4p12- p16 band from human
      chromosomes were microdissected and amplified as probe pools. The origins of the
      PCR products were determined by chromosome fluorescence in situ hybridization.
      The PCR products and pUC19 were digested by Xho I and Sal I respectively, and
      linke up. The DH5alpha were transformed by the recombinated vectors as the
      specific band libraries. The inserts were digested by EcoR I and Hind III, then
      measured by electrophoretic analysis. And the copies of inserts were identified
      by in situ bacterial colony hybridization with genomic DNA. RESULTS: All the
      three probe pools showed the special yellow-green signals in their
      microdissection responsible bands. The sizes of DOP-PCR products ranged from
      300bp to 1800bp. 3q21-q22 probe pool generated about 1.2 x 10(4) clones. The
      average size of inserts was about 420bp by analysis of 30 positive clones. The
      rate of single-copy and low-repeated sequences was about 81%(178/220), while the
      rate of middle-repeated and high- repeated sequences was about 19%(42/220).
      CONCLUSION: The results proved that the modified microdissection combining DOP
      PCR technique provided a simple and efficient method to construct the human
      chromosome band-specific probe pools and might contribute to gene cloning and
      complete sequencing of human genome.

PMID- 9621125
TI  - [Chromosome assignment of a novel microsatellite polymorphic marker (D14S1435) by
      fluorescence in situ hybridization].
AB  - OBJECTIVE: Chromosome assignment of a novel microsatellite marker (D14S1435)
      containing CA repeats and showing 11 alleles and 0.85 of PIC value in Chinese
      population) isolated from microdissected human chromosome 14q24.3 DNA library by
      fluorescence in situ hybridization(FISH). METHODS: The polymorphic marker was
      used as probe to screen a human Lambda/DASH genome library, a positive clone was
      isolated and the recombinant phage DNA was extracted as primary material. The
      insert was recovered through BamH I digestion to complete and low melting point
      agarose gel electro- phoresis, after processed with Sau3A I the probe was
      prepared by linker- catch PCR method and the following fluorescence in situ
      hybridization(FISH) was conducted to metaphase chromosomes. RESULTS: this novel
      STR was precisely mapped to human chromosome 14q24.3, and this demonstrated the
      validity of isolating chromosome band-specific genetic markers from probe pool
      made by chromosome microdissection. CONCLUSION: Confirmed by chromosome
      fluorescence in situ hybridization, the novel STR obtained by chromosome
      microdissection, PCR and subcloning method was really from the micro- dissected
      region. This not only increases the numbers of genetic markers used for linkage
      analysis in the region,but also provides a novel valuable genetic marker for the
      gene diagnosis and gene cloning of the possible disease-causing genes located in
      the region of 14q24.3.

PMID- 9621126
TI  - [Detection of minimal residual disease in acute lymphoblastic leukemia using PCR
      molecule hybridization of RNA transcripts].
AB  - OBJECTIVE: To detect acute lymphoblastic leukemia's(ALL's) minimal residual
      disease(MRD) rapidly and effectively. METHODS: In this assay, the gamma T-cell
      receptor gene rearrangements serve as marker genes. The gene rearrangements are
      amplified from the diagnostic specimens using a consensus V segment primer and a
      consensus J segment primer to which the promoter T7 RNA polymerase has been
      appended. The PCR product from this amplification is transcribed into a
      radiolabeled RNA probe. The opposite DNA strand is transcribed into test RNA from
      the PCR product of different staged specimens. The test RNA is hybridized with
      the probe, and later the digestion with RNase A, Polyacrylamide gel
      electrophoresis and autoradiography are in progress. RESULTS: According to the
      mechanism, the perfectly matched RNA duplex can prevent the digestion of RNase A,
      and the presence of the leukemia cells in the test specimen can be determined.
      Logarithmical dilution experiments with DNA of a cell line from ALL have shown
      that this assay's sensitivity is at the 10(-5) level. Minimal residual disease
      was successfully detected in a case of ALL during its complete remission stage.
      But if the probe and test RNA are not from the same individual, the results of
      this kind of cross hybridization are negative. CONCLUSION: The above results
      suggest that this assay can become an effective measure in the detection of ALL
      MRD clinically.

PMID- 9621127
TI  - [The stability of freeze-drying lysosomal enzymes].
AB  - OBJECTIVE: Enzyme assays for the diagnosis of lysosomal storage diseases have
      been underway in China only in a few laboratories, and the specimens for enzyme
      assay must not be inactivated by environmental factors. To solve the problem, the
      stability of freeze-drying lysosomal enzymes was tested. METHODS: Three pools for
      samples were set up: control leucocytes pool and plasma pool(40 individuals in
      each pool), control fibroblasts pool( 3 cell lines). 4 groups of different
      dispositions of samples were designed for the pools:(1)pellets or plasma directly
      stored at -80 degrees C as routine(non-freeze-drying group or N);(2)after freeze
      drying, pellets or plasma immediately stored at -80 degrees C (0 week or 0W); (3)
      after freeze-drying, pellets or plasma stayed at room temperature for 1
      week(simulated mail) then stored at -80 degrees C (1 week or 1W);(4) the same
      with 1W but 3 weeks at room temperature(3 weeks or 3W). Microassay for enzyme
      activity was employed: 20 enzymes in leucocytes pool, 14 enzymes in fibroblasts
      pool and 7 in plasma pool. RESULTS: Enzyme activities among 4 groups in each
      sample pool were compared. Single factor analysis of variance (F test) showed no
      significance of differences (P>0.05) among 4 groups in leucocytes and fibroblasts
      pool, but highly significant differences (P<0.01) among 4 groups in plasma pool.
      "t test" showed no significance of differences (P> 0.05) between N and 3W in
      leucocytes and also fibroblasts pool, but very significant differences (P<0.01)
      between N and 3W in plasma pool. CONCLUSION: The results suggest that freeze
      drying samples from leucocytes and fibro- blasts can provide a stable resource
      for enzyme assay and be simple for transportation of the diagnostic samples.
      Though freeze-drying is not appropriate for the plasma samples, it is still
      applicable for wide use since only a few kinds of lysosomal enzyme being
      indicated to use plasma for enzyme assay.

PMID- 9621128
TI  - [Interference of human processed pseudogene and corresponding counter-measures in
      reverse transcriptase-polymerase chain reaction].
AB  - OBJECTIVE: This study aimed to set up an effective method to find the
      interference of processed pseudogene and overcome it in RT-PCR. METHODS: Using RT
      PCR methods, the authors amplified the cytokeratin 19 cDNA or DNA sequence in
      human lung squamous cell carcinoma samples. RESULTS: They could find the
      influence of pseudogene through performing genomic DNA and nonreversed
      transcribed RNA controls. By digesting the extracted RNA sample with RNase-free
      DNase or regulating the annealing temperature based on mismatched primers, they
      could effectively eliminate the interference. CONCLUSION: The presence of
      processed pseudogene usually interferes in the experimental protocol in RT-PCR.
      This problem can be resolved with the method aforementioned.

PMID- 9621129
TI  - Effectiveness and efficiency of methods of dialysis therapy for end-stage renal
      disease: systematic reviews.

PMID- 9621130
TI  - Antimicrobial prophylaxis in colorectal surgery: a systematic review of
      randomised controlled trials.

PMID- 9621131
TI  - T cells in systemic lupus erythematosus.

PMID- 9621132
TI  - Alteration of cytokine genes and bcl-2 expression following immunotherapy with
      intralesional IFN-gamma in a patient with tumor-stage mycosis fungoides.
AB  - BACKGROUND: Interferon-gamma (IFN-gamma) is used in the treatment of tumor stage
      mycosis fungoides (MF), whereas its mechanism is still unknown. We have
      previously shown that treatment with intralesional IFN-gamma induced tumor
      regression. OBJECTIVE: To explore the possibility that IFN-gamma may alter the
      cytokine expression by tumor cells, we studied cytokine gene expression in a
      tumor nodule of MF. METHODS: By using the reverse transcriptase-polymerase chain
      reaction, Th1- and Th2-type cytokine mRNA expression was examined before and
      after intralesional IFN-gamma therapy. Additionally, we examined bel-2 protein
      expression on tumor cells. RESULTS: We found weak mRNA expression of interleukin
      4 (IL-4) and IL-5, and strong expression of IL-6, IL-10 and IFN-gamma before
      therapy. After successful treatment of intralesional IFN-gamma, mRNA expression
      of IL-5, IL-6 and IL-10 were significantly reduced and IL-2 mRNA was mildly
      induced. Culture for 24 h of tumor cells with IFN-gamma showed upregulation of IL
      2 mRNA and downregulation of IL-6 mRNA expression. bcl-2 expression was
      significantly decreased after successful intralesional IFN-gamma therapy,
      photochemotherapy (PUVA) and radiation therapy. CONCLUSION: These data suggest
      that IFN-gamma induces tumor regression by affecting cytokine gene expression in
      MF tumor lesions. The reduced bcl-2 expression did not seem to be induced by a
      direct immunological affect of IFN-gamma, but to represent a nonspecific result
      of tumor regression after successful treatment.

PMID- 9621133
TI  - c-myc is not useful as prognostic immunohistochemical marker in cutaneous
      melanoma.
AB  - BACKGROUND: Several studies indicate that immunohistochemical detection of the c
      myc oncogene might serve as an additional prognostic marker in malignant
      melanoma. OBJECTIVE: To study c-myc expression in paraffin-embedded cutaneous
      melanoma and to correlate to metastatic potential and onset of metastases.
      METHODS: Cytoplasmic c-myc protein expression was visualized using the APAPP
      method, and reactivity (percent total tumor cells stained) was assessed in 62
      formalin-fixed paraffin-embedded primary cutaneous melanomas (21 not
      metastasizing, mean Breslow 3.0 +/- 2.9 mm, 41 metastasizing, mean Breslow 3.1 +/
      3.0 mm) and 24 metastases of the same patients. RESULTS: There was no
      significant difference of c-myc reactivity in cutaneous melanoma who did not
      metastasize (n = 21, c-myc reactivity 32.7 +/- 19.3%, follow-up 10.6 +/- 1.8
      years) and primaries who metastasized (n = 41, c-myc reactivity 27.7 +/- 22.4%, p
      = 0.29). This finding was independent of the thickness of the primary and was
      found within thin cutaneous melanoma with a Breslow, < 0.75 mm (range 0.24-0.65
      mm, n = 20, c-myc reactivity 29.1 +/- 15.7%, p = 0.32) or within thick cutaneous
      melanoma with a Breslow > 1.5 mm (range 1.6-11 mm, n = 41, c-myc reactivity 29.6
      +/- 23.8%, p = 0.46). No correlation of c-myc expression between thin cutaneous
      melanoma, thick cutaneous melanoma (p = 0.83) or metastasizing primaries and
      their metastases (n = 24, c-myc reactivity 29.3 +/- 22%) was found (p = 0.64).
      The time period until development of first metastasis did not correlate with the
      percentage of cells expressing c-myc in the primary (p = 0.56). CONCLUSION: c-myc
      expression is independent of metastatic potential and onset of metastases and,
      therefore, does not serve as a prognostic immunohistochemical marker in primary
      cutaneous melanoma.

PMID- 9621134
TI  - Detection of human papillomavirus type 33 DNA in extragenital Bowen's disease
      with the polymerase chain reaction.
AB  - BACKGROUND: Data on the association of human papillomavirus (HPV) infection with
      extragenital Bowen's disease are very scarce. OBJECTIVE: To evaluate the
      prevalence of HPV infection in extragenital Bowen's disease showing
      histologically a number of koilocytes in the lesional epidermis, we studied
      formalin-fixed, paraffin-embedded tissues of 9 such cases. METHODS: HPV DNA was
      studied in such samples by the polymerase chain reaction (PCR) and in situ
      hybridization. RESULTS: Despite negative results with in situ hybridization, the
      PCR with HPV type 33 primer detected the presence of virus DNA in 2 out of 9
      cases. CONCLUSION: As far as we know, this is the first report of the detection
      of HPV type 33 DNA in the lesional skin of extragenital Bowen's disease. The
      prevalence of HPV infection in extragenital Bowen's disease may be higher than
      expected, especially in cases histologically showing many koilocytes in the
      lesional epidermis.

PMID- 9621135
TI  - Polythelia pilosa: a particular form of accessory mammary tissue.
AB  - BACKGROUND: The old Kajawa classification which considered eight possible forms
      of aberrant mammary tissue has been recently modified into a simpler one that
      considers this condition only when there is glandular parenchyma or when the
      aberrant tissue is not a glandular tissue but a nipple, an areola or both. This
      new classification disregards 'polythelia pilosa' defined as an 'isolated patch
      of hairs only'. OBJECTIVE: To demonstrate that polythelia pilosa is at least a
      marker of subjacent accessory mammary tissue and, consequently, that the term
      should be incorporated into the current classification. METHODS: Among 72 cases
      of aberrant or accessory mammary tissue, we have studied 14 cases (7 men and 7
      women) that were clinically diagnosed as 'visible isolated patches of hairs,
      apparently without pigmentation nor structures of areola or nipple'. We excised
      such isolated patches in 3 women. RESULTS: The histopathological examination
      showed an acanthotic and hyperpigmented epithelium with central depression closed
      by keratin plugs; in the dermis there were follicles with hairs surrounded by
      hypertrophic sebaceous glands. In the deepest portion, abundant secretory
      glomerules and excretory ducts of apocrine gland type could be observed.
      CONCLUSION: Since the biopsy of isolated patches of hairs demonstrated structures
      of either areolar or apocrine glandular tissue, we think that the term
      'polythelia pilosa' should be reinstated into the classification as it is at
      least a marker of true aberrant mammary structures in men and hirsute women.

PMID- 9621136
TI  - Comparison of conventional photographs and telephonically transmitted compressed
      digitized images of melanomas and dysplastic nevi.
AB  - BACKGROUND: One of the most difficult problems in the in vivo diagnosis of
      cutaneous tumors is the differentiation clinically between early malignant
      melanoma (MM) and atypical (dysplastic) melanocytic nevi (AMNs) because these
      lesions share clinical features. High-quality digital imaging systems and store
      and-forward technology have the potential for use in a teledermatology system
      with which experts would be able to immediately transmit their diagnostic
      opinions concerning these challenging lesions. OBJECTIVE: The main purpose of
      this study was to determine if the clinical and dermoscopic diagnoses and the
      dermoscopic features of AMN and early MM are unaltered after telephonic
      transmission of their digitized images. METHODS: Conventional and dermoscopic
      photographic transparencies of 22 AMNs and 9 early MMs, viewed on rearview
      projectors and then scanned, compressed, transmitted (Internet) and viewed on
      color monitors, were evaluated. RESULTS: The concordance in the diagnosis of AMN
      and of early MM by all four observers, both clinically and dermoscopically, when
      comparing rearview-projected conventional transparency slides to transmitted,
      compressed, digitized images, was high. For most specific dermoscopic features,
      the concordance was good, although less so for the presence or absence of some
      dermoscopic creatures, namely 'dots', 'blue/gray' color and 'red' color.
      CONCLUSION: The results reported support the conclusion that Internet
      transmission of digitized images of MMs and AMNs retains sufficient information
      for diagnostic purposes. This study is a step in the creation of an international
      teledermoscopy network for pigmented cutaneous lesions.

PMID- 9621137
TI  - Extracorporeal photopheresis of cutaneous T-cell lymphoma is associated with
      reduction of peripheral CD4+ T lymphocytes.
AB  - BACKGROUND: Extracorporeal photopheresis (ECP) has been successfully introduced
      for the treatment of cutaneous T-cell lymphoma; however, the mechanism(s) of its
      action is (are) unknown. OBJECTIVE: To investigate the effects of ECP on the
      immune system of patients with cutaneous T-cell lymphoma. METHODS: Clinical
      response and changes of lymphocyte subpopulations in 20 patients with cutaneous T
      cell lymphoma under ECP monotherapy or combined regimens were evaluated and
      compared after 3, 6 and 12 ECP cycles. RESULTS: Thirteen of 20 patients showed a
      > or = 50% reduction of skin lesions after 6-12 ECP cycles. An overall T
      lymphocyte reduction was assessed with a balanced CD4+ T-helper and CD8+ T
      suppressor cell decrease in responders. In contrast, there was a trend of CD4+ T
      helper cell increase in nonresponders which could result from the failure of
      treatment to control the natural course of the disease. The CD4+/CD8+ ratios were
      1.6 at baseline and 1.4 after 12 cycles in responders, while they increased from
      1.7 to 4.1 in nonresponders, respectively (p = 0.47). In addition, there was an
      overall decrease in the CD57+/CD8+ T-cell subpopulation mostly due to a reduction
      in the responder group. CONCLUSION: The marked differences detected in certain T
      cell subpopulations suggest an effect of ECP on peripheral T lymphocytes and,
      especially, on CD4+ cells.

PMID- 9621138
TI  - Management of severe scleroderma with long-term extracorporeal photopheresis.
AB  - BACKGROUND: The management of systemic sclerosis remains unsatisfactory. Thus
      far, the action of extracorporeal photopheresis (ECP) in severe systemic
      scleroderma has been evaluated in short-term studies, and only limited experience
      has been obtained with long-term application. OBJECTIVE: The aim of the present
      study was to evaluate prospectively the long-term effect of ECP in a group of 16
      patients suffering from severe scleroderma, showing visceral involvement and
      progressive clinical course. METHODS: Fourteen patients with systemic scleroderma
      involving several organs, 1 with CREST syndrome and another with scleroderma
      myositis overlap syndrome were treated with ECP over a period of 6-45 months. In
      3 cases, gamma-IFN was additionally administered. Skin and visceral involvement
      were assessed by evaluating a series of clinical criteria and results from
      laboratory, imaging and functional tests. RESULTS: Overall, clear improvement was
      encountered in 6 patients, mixed response in 2, stable disease in 3 and
      continuing progressive course in 5 patients. Four out of 6 patients with
      improvement were treated with ECP early after onset of scleroderma (< or = 2
      years), whereas all patients with a progressive course under ECP had had
      scleroderma for longer than 2 years. Immunosuppressive drugs previously
      administered could be reduced or fully withdrawn under ECP treatment in 5
      patients, but additional oral medication was introduced in 4 patients due to
      disease progression. Addition of gamma-IFN to ECP did not reveal further benefit.
      No side-effects were recorded under ECP treatment. CONCLUSIONS: Based on this
      observation, we believe that long-term ECP represents an effective treatment
      modality in severe scleroderma particularly when started early, with
      stabilization of the disease course and partial remission of the cutaneous
      findings, whereas visceral involvement, if present, may rarely improve.

PMID- 9621139
TI  - Anti-inflammatory effect of hamamelis lotion in a UVB erythema test.
AB  - BACKGROUND: Although Hamamelis virginiana has long been used in the traditional
      treatment of skin diseases, there are few controlled clinical studies defining
      the extent of its anti-inflammatory action. OBJECTIVE: The anti-inflammatory
      efficacy of pH5 Eucerin aftersun lotion with 10% hamamelis distillate, the
      vehicle and a prior aftersun formulation were tested in 30 healthy volunteers
      using a modified UVB erythema test as model of inflammation. METHODS: Four UVB
      doses ranging from 1 to 2 MED were evaluated in each subject. Test fields on the
      back were treated occlusively for 48 h following irradiation. Chromametry and
      visual scoring were used to determine the degree of erythema in the treated
      fields and an untreated, irradiated control field 7, 24 and 48 h after
      irradiation. RESULTS: Erythema suppression ranged from approximately 20% of 7 h
      to 27% at 48 h in the hamamelis fields. A suppression of 11-15% was recorded in
      the fields treated with the other lotions. Significant differences were noted
      between hamamelis and these lotions. CONCLUSION: These data provide evidence for
      an anti-inflammatory action of the aftersun lotion with 10% hamamelis and support
      the usefulness of the UVB erythema test with multiple UV doses for the testing of
      nonsteroidal anti-inflammatory agents.

PMID- 9621140
TI  - Itraconazole in the treatment of onychomycosis: a double-blind comparison with
      miconazole.
AB  - BACKGROUND: In recent years, itraconazole pulse therapy for onychomycosis has
      been developed [three 1-week pulses with itraconazole 400 (2 x 200) mg daily
      every month]. This has proved an effective and safe regimen which requires only
      50% of the medication used for continuous dosing schedules. Parallel to the
      development of the new dosage schedule, additional studies were conducted to
      further document the safety and efficacy of itraconazole 200 mg once daily for 3
      months to treat onychomycosis. OBJECTIVE: To compare the safety of itraconazole
      200 mg once daily for 3 months, with or without itraconazole 200 mg once weekly
      for a further 3 months, with that of miconazole cream twice daily for 6 months,
      in the treatment of onychomycosis. Treatment efficacy was compared as a secondary
      objective. METHODS: In this multicenter, double-blind study, patients were
      randomized to receive itraconazole 200 mg once daily for 3 months followed by
      either itraconazole 200 mg once weekly for 3 months (ITR-ITR group, n = 599) or
      oral placebo once weekly for 3 months (ITR-PLAC group, n = 613), or to receive
      miconazole cream twice daily for 6 months (MIC-MIC group, n = 396). The primary
      variable was elevation of alanine amino-transferase (ALT) concentration above 50
      U/I. RESULTS: Overall incidence of elevation of ALT concentration above 50 U/I,
      adverse events and rate of withdrawal because of adverse events were low and
      similar in the three treatment groups. Efficacy was significantly greater in the
      ITR groups than the MIC-MIC group. CONCLUSION: Itraconazole and miconazole were
      well tolerated and had no significant effect on liver function, but itraconazole
      was significantly more effective.

PMID- 9621141
TI  - Recombinant interferon beta gel as an adjuvant in the treatment of recurrent
      genital warts: results of a placebo-controlled double-blind study in 120
      patients.
AB  - BACKGROUND: Pilot studies of adjuvant therapy with topically applied interferons
      (IFN) have shown promising results in reducing the recurrence of condylomata
      acuminata (CA). OBJECTIVE: The aim of this multicenter placebo-controlled, double
      blind study was to confirm the efficacy and safety of topically applied IFN in a
      large sample of patients. METHODS: After removal of CA by CO2 laser surgery,
      electrocautery or cryosurgery, 120 patients applied either recombinant IFN-beta
      (0.15 or 1.0 x 10(6) IU/g) or placebo gel to the affected areas 5 times daily for
      4 weeks. The patients were followed for a total of 24 weeks or until recurrence
      of CA was observed, respectively. RESULTS: In the 105 patients evaluated for
      efficacy after 24 weeks, recurrence rates were 75% (27/36 patients) in the
      placebo group, 62% (21/34) in the 1.0 x 10(6) IU/g group (n.s.) and 54% (19/35)
      in the 0.15 x 10(6) IU/g group (p = 0.034). Only few mild adverse events were
      noted, which were almost limited to the application site. CONCLUSION: Topical
      application of gel containing 0.15 x 10(6) IU/g recombinant IFN-beta is safe and
      appears to reduce the recurrence of CA after surgical treatment.

PMID- 9621142
TI  - Immediate reaction to roxithromycin and prick test cross-sensitization to
      erythromycin and clarithromycin.
AB  - Allergic reactions to macrolides appear to be very rare. Only a few cases of
      fixed drug eruption or urticaria due to the administration of erythromycin have
      been reported. Cross-reaction between the different macrolides have not yet been
      published. We report a case of a 31-year-old female patient who developed
      generalized urticaria and tachycardia shortly after administration of
      roxithromycin (Rulid). Immediate-type hypersensitivity was confirmed by positive
      prick test reactions to roxithromycin and the chemically closely related
      macrolides erythromycin and clarithromycin.

PMID- 9621143
TI  - Carcinoma of the glans penis arising 20 years after lichen sclerosus.
AB  - Lichen sclerosis (LS) is an inflammatory disease of incompletely characterized
      pathogenesis. The relation between LS and carcinoma is well known in women, but
      in men it is still a matter of debate whether LS is a premalignant lesion or not.
      We describe a case of LS of the glans penis which occurred in 1976. Within the
      next 20 years, the patient developed carcinoma at this site.

PMID- 9621144
TI  - Hereditary hypotrichosis simplex.
AB  - Hypotrichosis is a relatively common feature of a number of complex hereditary
      syndromes. However, the isolated variant, called hereditary hypotrichosis simplex
      (HHS), is especially uncommon. We present a Spanish family with 8 of 19 persons
      covering 4 generations affected by HHS. No associated ectodermal or other defects
      were noted. The pedigree was compatible with an autosomal dominant inheritance
      with variable penetrance.

PMID- 9621145
TI  - Larva currens: the usefulness of the agar plate method.
AB  - Creeping eruption caused by Strongyloides stercoralis is called larva currens,
      while those caused by other parasites are called larva migrans. To detect the
      parasite, the direct smear method was used. However, this method is not very
      sensitive in detecting S. stercoralis. A 62-year-old male with polyarteritis
      nodosa cutanea had an erythematous creeping eruption in various regions, such as
      his lumbar region, abdomen and thigh. The diagnosis of larva currens was made by
      the clinical appearance and the detection of S. stercoralis in his feces using
      the direct smear method and the agar plate method. This is the first reported
      case of larva currens in Japan. The agar plate method was useful and more
      sensitive than the usual direct smear method for detecting the S. stercoralis in
      feces and for elucidating the effects of treatment with antiparasitic drugs.

PMID- 9621146
TI  - Pustular vasculitis of the hands. Report of two men.

PMID- 9621147
TI  - Digital necrosis and lupus-like syndrome preceding ovarian carcinoma.
AB  - Since 1967, about 40 cases of digital necrosis associated with neoplasia have
      been reported. We report a new case of digital necrosis associated with an
      ovarian carcinoma and with a lupus-like syndrome. Immunologic cross-reactivity to
      tumoral antigen could explain the lupus-like syndrome.

PMID- 9621148
TI  - Overlap of reticulate acropigmentation of Kitamura, acropigmentation of Dohi and
      Dowling-Degos disease in four generations.
AB  - A large kindred is being reported in which reticulate acropigmentation of
      Kitamura (RAPK) and acropigmentation of Dohi (APD) were associated with features
      of Dowling-Degos disease (DDD). The pedigree was traced through four generations
      and 50% of the members were found to be affected. RAPK, APD and DDD are inherited
      as an autosomal dominant trait with variable penetrance. The differentiation and
      overlap/association of RAPK, APD and DDD is discussed.

PMID- 9621149
TI  - Lectitis purulenta et granulomatosa (granulomatous purulent nail bed
      inflammation).
AB  - A granulomatous purulent nail bed inflammation of the great toenails in a 69-year
      old female patient is described. The successful treatment consisted of intra- and
      perilesional corticosteroide injections in addition to systemic antibiotic
      treatment.

PMID- 9621150
TI  - Photoallergic contact dermatitis due to combined UVB (4-methylbenzylidene
      camphor/octyl methoxycinnamate) and UVA (benzophenone-3/butyl
      methoxydibenzoylmethane) absorber sensitization.
AB  - In a 71-year-old male Caucasian patient with persistent eczema on light-exposed
      skin, photocontact allergy was demonstrated to the UV filter substances 4
      methylbenzylidene camphor (UVB), octyl methoxycinnamate (UVB), benzophenone-3
      (UVA) and butyl methoxydibenzoylmethane (UVA) present in sunscreen products used
      by the patient over several years. A significantly reduced UVB sensitivity of 25
      mJ/cm2 in this patient (normal minimal erythema dose in our laboratory = 70-130
      mJ/cm2) was considered an early indication of a persistent light reaction.
      Topical anti-inflammatory treatment over 2 weeks together with consequent
      application of a sunscreen containing Mexoryl SX/titanium dioxide led to complete
      remission. Taking into account the widespread use of the above UV filter
      substances not only in sun protection products, but also in cosmetics such as
      antiaging lotions and day care products, the possible risk of allergy to these
      chemicals has to be taken seriously. The substitution of known photocontact
      sensitizers in UV filters by photostable compounds and detailed product
      information are the basis of preventive strategies.

PMID- 9621151
TI  - Superficial granulomatous pyoderma.
AB  - Superficial granulomatous pyoderma (SGP) is a form of pyoderma gangrenosum (PG)
      characterized by superficial ulceration and chronic course. To date it has been
      described as a condition with specific histopathological findings. We report a
      new case with clinical characteristics of SGP and describe why we believe that
      the histological changes previously described are not typical of this entity.

PMID- 9621152
TI  - Acrocyanosis induced by interferon alpha(2a).
AB  - A 56-year-old woman with mycosis fungoides developed acrocyanosis each time
      treatment with interferon alpha(2a) was started. Acrocyanosis disappeared after
      discontinuing therapy. Immunological study performed while acrocyanosis was
      present showed elevated antinuclear antibody (ANA) titers and circulating immune
      complex levels. Long-term interferon treatment has been related to autoimmune
      side effects. Raynaud's phenomenon has been observed in patients undergoing
      interferon treatment associated with elevated ANA titers, to cryoglobulinemia or
      to arterial occlusion. Acrocyanosis has never before been described as side
      effect in patients undergoing this treatment. We believe that our patient's
      acrocyanosis must be considered a side effect of interferon.

PMID- 9621153
TI  - Mucin deposition in a prayer nodule on the forehead.

PMID- 9621154
TI  - Trends in melanoma in whites living in the French West Indies (Martinique)

PMID- 9621155
TI  - Allergic contact dermatitis due to lanoconazole with no cross-reactivity to other
      imidazoles.

PMID- 9621156
TI  - An unusual case of multiple epidermal finger cysts.

PMID- 9621157
TI  - Fixed drug eruption due to metronidazole and tinidazole without cross-sensitivity
      to secnidazole.

PMID- 9621158
TI  - Cutis marmorata telangiectatica congenita with multiple congenital anomalies.
      Further clues for a teratogenic cause.

PMID- 9621159
TI  - Pyoderma gangrenosum associated with Fanconi's anemia.

PMID- 9621160
TI  - Increased serum soluble Fas, tumor necrosis factor alpha and interleukin 6
      concentrations in generalized pustular psoriasis.

PMID- 9621161
TI  - The rise of English in Dermatology.

PMID- 9621162
TI  - Trichodynia.

PMID- 9621163
TI  - Telogen effluvium and trichodynia.

PMID- 9621164
TI  - [General problems in the study of the mutagenic properties of drugs].
AB  - The article deals with the results characterizing the state of Russian and
      foreign elaborations in the study of genotoxic effects of drugs and
      immunobiological agents. Particular attention is placed on general problems of
      strategy and tactics in the study of mutagenicity of drugs the solution of which
      is insufficiently substantiated or insufficiently discussed in the literature.
      The perspective problems of research into the field of genotoxicity of drugs are
      discussed.

PMID- 9621165
TI  - [The participation of the dorsal hippocampus in the antianxiety action of
      melatonin and diazepam].
AB  - The pineal hormone melatonin and the tranquilizer diazepam given in an equal dose
      (0.1 mg/kg) demonstrated an anxiolytic effect on a model of a conflict situation
      in rats. Damage to the dorsal hippocampus produced a similar effect and the
      anxiolytic activity of the drugs under study was removed against this background.

PMID- 9621166
TI  - [The effects of medazepam on memory trace reproduction during learning and
      amnesia in aggressive and submissive C57Bl/6J mice].
AB  - Experiments were conducted on C57B1 mice to study the role of the social status
      on the reproduction of a conditioned reaction of passive avoidance and the effect
      of medazepam on the processes of reproduction. Aggressive and submissive animals
      were selected according to the test for agonistic confrontations. No effect of
      the animals' social status on the formation of a conditioned habit was revealed,
      but a significant increase in the level of defecation was recorded in the
      aggressive mice. Medazepam administration before the test reduced the
      reproduction of the conditioned reaction only in the control mice. An amnestic
      effect blocked reproduction in control and submissive mice but did not change it
      in the aggressors. Medazepam restored the amnestic memory trace only in
      submissive individuals. In aggressive mice it reduced the emotional response but
      did not change reproduction. The data obtained suggest that variations of the
      social status determine both the behavioral responsiveness to training and the
      changes in reproduction in response to medazepam.

PMID- 9621167
TI  - [The pharmacological differences between kynurenine- and korazol-induced seizures
      (the participation of GABA-B receptors and dopamine)].
AB  - In experiments of male SHR (nonbred) and C57B1/6 mice [correction of rats]
      bicucullin intensified corasole-induced convulsions but had no effect on
      kynurenine convulsions, removed the anticonvulsive effect of phenibut against
      kynurenine and did not affect the anticonvulsive effect of diazepam against
      corasole. Phenibut and baclofen reduced the anticonvulsive effect of diazepam
      against corasole and caffeine. Haloperidol increased kynurenine-induced
      convulsions and had no effect on those caused by corasole. Dopamine removed the
      effect of haloperidol. Haloperidol and 6-oxydopamine weakened the sedative effect
      of phenibut. Blockade of GAMAB-receptors and weakening of dopaminergic activity
      are important in the mechanisms of kynurenine convulsions, and blockage of GABAA
      receptors unrelated to it is important in the mechanisms of corasole convulsions.
      A functional antagonism in anticonvulsive activity may exist between these
      receptors. Bicucullin may probably have an effect both on GABAA- and GABAB
      receptors.

PMID- 9621169
TI  - [The cardioprotective action of preparations of biotechnological cytochrome c in
      acute myocardial ischemia].
AB  - The cardioprotective effect of cytochrome c preparations was evaluated according
      to the test for restriction of the size of the myocardial infarct and the effect
      on the course of acute myocardial ischemia in acute experiments on dogs.
      Cytochrome c of biotechnological and animal origin and hemtetradecapeptide caused
      a marked decrease in the size of the myocardial necrosis in experiments on rats:
      from 68 +/- 4.3% in the control to 32 +/- 3.4, 46 +/- 8.3 and 44 +/- 4.7%,
      respectively. In dog experiments the cytochrome c agents reduced the intensity of
      dp/dt decline and decreased the collateral coronary blood flow in acute
      myocardial ischemic. They produced a beneficial effect on heart bioenergetics,
      namely, reduced the lactate level in blood flowing from the zone of the ischemia
      and glucose consumption by the ischemic myocardium. The cardioprotective effect
      of biotechnological cytochrome c hemtetradecapeptide was practically identical to
      the effect of the enzyme of animal origin.

PMID- 9621170
TI  - [The action of sodium oxybutyrate and emoxypin on the functional state of the
      adrenaline-damaged myocardium in an experiment].
AB  - The effect of agents possessing antihypoxic and antioxidant activity, namely
      sodium oxybutyrate and emoxypin, on the functional state of the heart muscle was
      studied in experiments on dogs with epinephrine necroses of the myocardium. A
      marked cardioprotective effect was produced by sodium oxybutyrate infused
      intravenously (200 mg/kg) either 10 min or 2 hrs after myocardial damage had been
      modelled and by emoxypin (4 mg/kg; 0.4 mg/kg) infused intravenously 30 min after
      the damage.

PMID- 9621171
TI  - [The pharmacology of the new combined anti-arrhythmia preparation metatsizin].
AB  - The combined antiarrhythmic effect of ethmosin and ethacisin in various dose
      ratios was studied in conscious dogs with two-stage ligation of the coronary
      artery (after Harris). A 6:1 ratio was found to be optimal for manifestation of
      the antiarrhythmic effect. In such a ratio of the doses the antiarrhythmic effect
      of a combination of ethmosin and ethacisin is essentially higher than the
      activity of each component. On the grounds of these data a combined
      antiarrhythmic drug methacisin was developed. It possesses a broad spectrum of
      antiarrhythmic activity. The drug is effective on models of arrhythmias specific
      of class I, III, and IV antiarrhythmics. Metacisin does not change hemodynamics
      and activity of the heart. Study of metacisin pharmacokinetics showed that it
      possesses bioavailability twice that of ethmosin tablets taken separately and
      four times that of ethasicin.

PMID- 9621172
TI  - [The anti-arrhythmia action of an extract of Rhodiola rosea and of n-tyrosol in
      models of experimental arrhythmias].
AB  - A daily 8-day course of Rhodiolae fluidum extract (1 ml/kg; ED50 = 0.43 ml/kg)--a
      preparation from the group of adaptogens caused a marked preventive
      antiarrhythmic effect on models of adrenaline and CaCl2-induced, but not
      acontine, arrhythmias. Aglycone--n-tyrosol demonstrated a lower antiarrhythmic
      activity (ED50 = 16 mg/kg) than that of Rhodiola extract.

PMID- 9621173
TI  - [The immunomodulating and antioxidant action of beta-carotene and essentiale in a
      lipid metabolic disorder].
AB  - Excessive supply of lipids to the organism of rats causes increase in lipid
      peroxidation, reduction of red cell energy status, the appearance in them of
      immunosuppressive properties, and inhibition of immunological reactivity.
      Administration of beta-carotene and essential corrects the biochemical status and
      immunological reactivity of the organism in alimentary lipid loading. beta
      Carotene cancels the immunosuppressive properties of light red blood cells,
      whereas essential induces the appearance of immunostimulating properties in the
      heavy cells.

PMID- 9621174
TI  - [The immunotropic properties of rifampicin and their correction].
AB  - The effect of rifampicin on antibody genesis depends on the dose, duration, and
      time of its administration in relation to the antigen, as well as on the
      character of immunosuppression. The antibiotic has no effect on delayed
      hypersensitivity and stimulates the activity of phagocytes, predominantly that of
      neutrophils. The effectiveness of rifampicin in experimental infection is
      maintained in treatment with cyclophosphane and azathioprine. When administered
      in combination with rifampicin and cytostatics methyluracil possesses a broader
      spectrum of immunostimulating activity than that of prodigiosin and levamisole.

PMID- 9621175
TI  - [The effect of the immunostimulating agent trimezon on the cells of the
      mononuclear phagocytosing system].
AB  - The effect of the immunostimulator trimeson of the 8-aza-gomogonan series on the
      cells of the mononuclear monocyte system was studied in C3H and ICR mice in
      vitro. Intraperitoneal injection of trimeson (50 mg/kg 1 x 10(-7)-1 x 10(6) M)
      inhibits, as a rule, the initial stages of the phagocytizing process but
      stimulates the bactericidal properties of the peritoneal phagocytes and their
      mechanisms of processing and destruction of the antigen material. In the system
      of adaptive transfer of donor splenocytes and peritoneal macrophages to
      recipients exposed to lethal radiation, trimeson (20 mg/kg intravenously, 50
      mg/kg per os) increases the immunogenic function of the mononuclear phagocytes in
      formation of the primary immune response to sheep erythrocytes.

PMID- 9621176
TI  - [The myelotoxicity of vepesid].

PMID- 9621177
TI  - [A semisynthetic flavonoid from the Baikal skullcap (Scutellaria baicalensis) as
      an agent to enhance the efficacy of chemotherapy in experimental tumors].

PMID- 9621178
TI  - [A preclinical trial of iodoantipyrine safety].
AB  - Detailed preclinical study of the safety of the new antiviral agent iodantipyrine
      was conducted. In LD50 parameters it was found to be related to moderately toxic
      drugs. Long-term administration in doses of 50, 100, and 250 mg/kg did not cause
      any essential functional and structural disorders in the organs and systems of
      rats and dogs. Iodantipyrine does not possess mutagenic and allergenic properties
      and does not affect the reproductive function.

PMID- 9621179
TI  - [The complement-activating action of modern x-ray contrast agents].
AB  - The study conducted proved that triombrast (dose dependently) > hexabrics >
      Ultravist > or = melitrast = omnipac in a concentration interval of 0.03-30.0 mg
      iodine/ml in vitro and in a dose interval of 0.5-2.0 g iodine/kg in vivo activate
      the complement system (CS) according to the alternative way in the blood of
      "sensitive" rats. The degree of CS activation by radiopaque agents (ROA) is
      significantly determined mathematically by their viscosity and relation of the
      number of iodine atoms to the number of ions or dissolved particles, and by their
      hydrophilic (for nonion CS) and osmotic (for ion monomeric CS) properties.

PMID- 9621180
TI  - [The effect of nootropic agents on brain mitochondrial function in the dynamics
      of craniocerebral trauma from the age aspect].
AB  - A craniocerebral trauma was modelled in experiments on one-month-old rats.
      Oxidative phosphorylation in the brain mitochondria was studied by polarography
      1, 4, 7 days and 4 weeks after the trauma. In the posttraumatic period the
      animals received piracetam (1 g/kg), picamilon (500 mg/kg), pyriditol (100
      mg/kg), pantogam (160 mg/kg), ACTH (5-10) (0.1 mg/kg), nooglutyl (25 mg/kg), and
      GVS (0.5 mg/kg). It was found that piracetam, picamilon, and nooglutyl have a
      protective effect on the function of the brain mitochondria during the course of
      a craniocerebral trauma. Nooglutyl surpasses all the other drugs in its influence
      on the effectiveness of oxidative phosphorylation of mitochondria in immature
      rats in the posttraumatic period.

PMID- 9621181
TI  - [Enterosorbents in the treatment of atherosclerosis].
AB  - The article lists, characterizes, and discusses the mechanism of the action of
      endosorbents possessing hypocholesteremic and hypolipidemic effects. Among them
      are natural endosorbents--food fibers (cellulose, hemicellulose, pectins, gum,
      mucus, lignin and chitin compounds, etc.); artificial specific affinin and
      nonspecific carbonic enterosorbents (carbonitrate family, granulated, fibrous),
      as well as silica (aerosil, polysorb). The effectiveness and pathogenetic
      expediency of correcting disorders of lipid metabolism in atherosclerosis with
      enterosorbents is substantiated.

PMID- 9621182
TI  - [Blood lipids, lipid peroxidation and the effect on them of antianginal
      preparations in ischemic heart disease patients].
AB  - The origin and development of ischemic heart disease (IHD) is attended with
      activation of lipid free-radical oxidation facilitating further advancement of
      the disease and with decrease of the organism's antioxidant protection. The
      antianginal drugs which are used in IHD treatment differ in their effect on the
      blood lipid composition and their peroxidation. beta-Adrenoblocking agents may
      cause proatherogenic disorders of the blood lipid graph, this increases the risk
      of IHD advancement. Long-acting nitro preparations are lipid-neutral. Calcium
      antagonists, mainly those of the nifedipin group, suppress LPO superactivity,
      possess a high antioxidant effect, and, probably, retard the advancement of
      coronary atherosclerosis and IHD.

PMID- 9621183
TI  - [The immunotropic activity of H1 antihistaminic preparations].
AB  - A survey of experimental and clinical data on the spectrum of immunotropic
      effects of H1-histamine blockers is presented. The mechanisms and role of the
      blockade of H1-histamine receptors in the immunotropic effect of the drugs are
      discussed.

PMID- 9621184
TI  - Emerging infectious diseases--Southeast Asia.

PMID- 9621185
TI  - Wild primate populations in emerging infectious disease research: the missing
      link?
AB  - Wild primate populations, an unexplored source of information regarding emerging
      infectious disease, may hold valuable clues to the origins and evolution of some
      important pathogens. Primates can act as reservoirs for human pathogens. As
      members of biologically diverse habitats, they serve as sentinels for
      surveillance of emerging pathogens and provide models for basic research on
      natural transmission dynamics. Since emerging infectious diseases also pose
      serious threats to endangered and threatened primate species, studies of these
      diseases in primate populations can benefit conservation efforts and may provide
      the missing link between laboratory studies and the well-recognized needs of
      early disease detection, identification, and surveillance.

PMID- 9621186
TI  - Accommodating error analysis in comparison and clustering of molecular
      fingerprints.
AB  - Molecular epidemiologic studies of infectious diseases rely on pathogen genotype
      comparisons, which usually yield patterns comprising sets of DNA fragments (DNA
      fingerprints). We use a highly developed genotyping system, IS6110-based
      restriction fragment length polymorphism analysis of Mycobacterium tuberculosis,
      to develop a computational method that automates comparison of large numbers of
      fingerprints. Because error in fragment length measurements is proportional to
      fragment length and is positively correlated for fragments within a lane, an
      align-and-count method that compensates for relative scaling of lanes reliably
      counts matching fragments between lanes. Results of a two-step method we
      developed to cluster identical fingerprints agree closely with 5 years of
      computer-assisted visual matching among 1,335 M. tuberculosis fingerprints. Fully
      documented and validated methods of automated comparison and clustering will
      greatly expand the scope of molecular epidemiology.

PMID- 9621187
TI  - Legal issues associated with antimicrobial drug resistance.
AB  - An effective public health strategy against the development of antimicrobial drug
      resistance needs to be informed by legal as well as scientific analysis. This
      article describes some legal issues arising from current efforts against
      antimicrobial resistance and underscores the interdependence between law and
      public health in these efforts.

PMID- 9621188
TI  - Rickettsial pathogens and their arthropod vectors.
AB  - Rickettsial diseases, important causes of illness and death worldwide, exist
      primarily in endemic and enzootic foci that occasionally give rise to sporadic or
      seasonal outbreaks. Rickettsial pathogens are highly specialized for obligate
      intracellular survival in both the vertebrate host and the invertebrate vector.
      While studies often focus primarily on the vertebrate host, the arthropod vector
      is often more important in the natural maintenance of the pathogen. Consequently,
      coevolution of rickettsiae with arthropods is responsible for many features of
      the host-pathogen relationship that are unique among arthropod-borne diseases,
      including efficient pathogen replication, long-term maintenance of infection, and
      transstadial and transovarial transmission. This article examines the common
      features of the host-pathogen relationship and of the arthropod vectors of the
      typhus and spotted fever group rickettsiae.

PMID- 9621189
TI  - Could myocarditis, insulin-dependent diabetes mellitus, and Guillain-Barre
      syndrome be caused by one or more infectious agents carried by rodents?
AB  - The numbers of small rodents in northern Sweden fluctuate heavily, peaking every
      3 or 4 years. We found that the incidence of Guillain-Barre syndrome and insulin
      dependent diabetes mellitus, as well as the number of deaths caused by
      myocarditis, followed the fluctuations in numbers of bank voles, although with
      different time lags. An environmental factor, such as an infectious agent, has
      been suggested for all three diseases. We hypothesize that Guillain-Barre
      syndrome, myocarditis, and insulin-dependent diabetes mellitus in humans in
      Sweden are caused by one or more infectious agents carried by small rodents.
      Also, a group of novel picornaviruses recently isolated from these small rodents
      is being investigated as the possible etiologic agent(s).

PMID- 9621190
TI  - Multidrug-resistant Mycobacterium tuberculosis: molecular perspectives.
AB  - Multidrug-resistant strains of Mycobacterium tuberculosis seriously threaten
      tuberculosis (TB) control and prevention efforts. Molecular studies of the
      mechanism of action of antitubercular drugs have elucidated the genetic basis of
      drug resistance in M. tuberculosis. Drug resistance in M. tuberculosis is
      attributed primarily to the accumulation of mutations in the drug target genes;
      these mutations lead either to an altered target (e.g., RNA polymerase and
      catalase-peroxidase in rifampicin and isoniazid resistance, respectively) or to a
      change in titration of the drug (e.g., InhA in isoniazid resistance). Development
      of specific mechanism-based inhibitors and techniques to rapidly detect multidrug
      resistance will require further studies addressing the drug and drug-target
      interaction.

PMID- 9621191
TI  - Hospitalizations for unexplained illnesses among U.S. veterans of the Persian
      Gulf War.
AB  - Persian Gulf War veterans have reported a variety of symptoms, many of which have
      not led to conventional diagnoses. We ascertained all active-duty U.S. military
      personnel deployed to the Persian Gulf War (552,111) and all Gulf War era
      military personnel not deployed (1,479,751) and compared their postwar
      hospitalization records (until 1 April 1996) for one or more of 77 diagnoses
      under the International Classification of Diseases (ICD-9) system. The diagnoses
      were assembled by the Emerging Infections Program, Centers for Disease Control
      and Prevention, and are here termed "unexplained illnesses." Deployed veterans
      were found to have a slightly higher risk of hospitalization for unexplained
      illness than the nondeployed. Most of the excess hospitalizations for the
      deployed were due to the diagnosis "illness of unknown cause" (ICD-9 code 799.9),
      and most occurred in participants of the Comprehensive Clinical Evaluation
      Program who were admitted for evaluation only. When the effect of participation
      in this program was removed, the deployed had a slightly lower risk than the
      nondeployed. These findings suggest that active-duty Gulf War veterans did not
      have excess unexplained illnesses resulting in hospitalization in the 4.67-year
      period following deployment.

PMID- 9621192
TI  - Agricultural use of Burkholderia (Pseudomonas) cepacia: a threat to human health?
AB  - In the past 2 decades, Burkholderia cepacia has emerged as a human pathogen
      causing numerous outbreaks, particularly among cystic fibrosis (CF) patients. One
      highly transmissible strain has spread across North America and Britain, and
      another between hospitalized CF and non-CF patients. Meanwhile, the organism has
      been developed as a biopesticide for protecting crops against fungal diseases and
      has potential as a bioremediation agent for breaking down recalcitrant herbicides
      and pesticides. However, B. cepacia is inherently resistant to multiple
      antibiotics; selection of strains "safe" for environmental application is not at
      present possible phenotypically or genotypically; molecular epidemiology and
      phylogenetic studies demonstrate that highly transmissible strains emerge
      randomly; and the organism has a capacity for rapid mutation and adaptation
      (facilitated by numerous insertion sequences), and a large, complex genome
      divided into separate chromosomes. Therefore, the widespread agricultural use of
      B. cepacia should be approached with caution.

PMID- 9621193
TI  - Haemophilus influenzae invasive disease in the United States, 1994-1995: near
      disappearance of a vaccine-preventable childhood disease.
AB  - We analyzed national Haemophilus influenzae (Hi) surveillance data from 1994 and
      1995 to describe the epidemiology of Hi invasive disease among persons of all
      ages. Serotype data were available for 376 (56%) of 669 reported Hi cases among
      children aged 4 years or younger; 184 (49%) were H. influenzae type b (Hib).
      Among children aged 4 or younger, incidence (per 100,000) of all Hi invasive
      disease was 1.8 in 1994 and 1.6 (p < 0.05) in 1995. Children aged 5 months or
      younger had the highest average annual incidence rate of Hib invasive disease
      (2.2 per 100,000); children aged 6 to 11 months had the next highest rate (1.2
      per 100,000)(p < 0.05). Of 181 children with Hib invasive disease whose age in
      months was known, 85 (47%) were too young (aged 5 months or younger) to have
      completed a primary series with an Hib-containing vaccine. Of the 83 children
      with known vaccination status who were eligible to receive a primary series (aged
      6 months or older), 52 (63%) were undervaccinated, and the remaining 31 (37%) had
      completed a primary series in which vaccine failed. Among persons aged 5 years or
      older with Hi invasive disease, the lowest average annual incidence was among
      those 20 to 39 years of age (0.15 per 100,000), and the highest was among those
      aged 80 years or older (2.26 per 100,000). Among persons aged 5 years or older,
      serotype data were available for 1,372 (71%) of the 1,940 Hi invasive disease
      cases; 159 (28%) of the 568 Hi cases with known serotype were due to Hib.

PMID- 9621194
TI  - Multiple-drug resistant enterococci: the nature of the problem and an agenda for
      the future.
AB  - Enterococci, leading causes of nosocomial bacteremia, surgical wound infection,
      and urinary tract infection, are becoming resistant to many and sometimes all
      standard therapies. New rapid surveillance methods are highlighting the
      importance of examining enterococcal isolates at the species level. Most
      enterococcal infections are caused by Enterococcus faecalis, which are more
      likely to express traits related to overt virulence but--for the moment--also
      more likely to retain sensitivity to at least one effective antibiotic. The
      remaining infections are mostly caused by E. faecium, a species virtually devoid
      of known overt pathogenic traits but more likely to be resistant to even
      antibiotics of last resort. Effective control of multiple-drug resistant
      enterococci will require 1) better understanding of the interaction between
      enterococci, the hospital environment, and humans, 2) prudent antibiotic use, 3)
      better contact isolation in hospitals and other patient care environments, and 4)
      improved surveillance. Equally important is renewed vigor in the search for
      additional drugs, accompanied by the evolution of new therapeutic paradigms less
      vulnerable to the cycle of drug introduction and drug resistance.

PMID- 9621195
TI  - Enteroaggregative Escherichia coli.
AB  - Enteroaggregative Escherichia coli (EAEC), an increasingly recognized cause of
      diarrhea in children in developing countries, has been particularly associated
      with persistent diarrhea (more than 14 days), a major cause of illness and death.
      Recent outbreaks implicate EAEC as a cause of foodborne illness in industrialized
      countries. The pathogenesis of EAEC infection is not well understood, but a model
      can be proposed in which EAEC adhere to the intestinal mucosa and elaborate
      enterotoxins and cytotoxins, which result in secretory diarrhea and mucosal
      damage. EAEC's ability to stimulate the release of inflammatory mediators may
      also play a role in intestinal illness.

PMID- 9621197
TI  - An apparently new virus (family Paramyxoviridae) infectious for pigs, humans, and
      fruit bats.
AB  - We isolated an apparently new virus in the family Paramyxoviridae from stillborn
      piglets with deformities at a piggery in New South Wales, Australia. In 1997, the
      pregnancy rate and litter size at the piggery decreased markedly, while the
      proportion of mummified fetuses increased. We found serologic evidence of
      infection in pigs at the affected piggery and two associated piggeries, in humans
      exposed to infected pigs, and in fruit bats. Menangle virus is proposed as a
      common name for this agent, should further studies confirm that it is a newly
      recognized virus.

PMID- 9621196
TI  - Campylobacter jejuni strains from patients with Guillain-Barre syndrome.
AB  - Guillain-Barre syndrome (GBS), an acute demyelinating peripheral neuropathy, may
      be triggered by an acute infectious illness; infection with Campylobacter jejuni
      is the most frequently reported antecedent event. In Japan, O:19 is the most
      common serotype among GBS-associated C. jejuni strains. To determine whether
      serotype O:19 occurs among GBS-associated strains in the United States and
      Europe, we serotyped seven such strains and found that two (29%) of seven GBS
      associated strains from patients in the United States and Germany were serotype
      O:19. To determine whether GBS-associated strains may be resistant to killing by
      normal human serum (NHS), we studied the serum susceptibility of 17 GBS- and 27
      enteritis-associated strains (including many O:19 and non-O:19 strains) using C.
      jejuni antibody positive (pool 1) or negative (pool 2) human serum. Using pool 1
      serum we found that one (6%) of 18 serotype O:19 strains compared with 11 (42%)
      of 26 non-O:19 strains were killed; results using pool 2 serum were nearly
      identical. Finally, 8 O:19 and 8 non-O:19 strains were not significantly
      different in their ability to bind complement component C3. Serotype O:19 C.
      jejuni strains were overrepresented among GBS-associated strains in the United
      States and Germany and were significantly more serum-resistant than non-O:19
      strains. The mechanism of this resistance appears unrelated to C3 binding.

PMID- 9621198
TI  - Probable human infection with a newly described virus in the family
      Paramyxoviridae. The NSW Expert Group.
AB  - After an apparently new virus in the family Paramyxoviridae was isolated from
      pigs in August 1997, an investigation was carried out to assess its risk for
      humans. More than 250 persons with potential exposure to infected pigs were
      tested serologically. Two piggery workers with intense occupational exposure had
      high convalescent-phase antibody titers to this new virus. In early June 1997,
      both workers had an influenzalike illness with rash; serologic testing showed no
      alternative cause. Strong evidence indicates that the two men became ill from
      this new virus, but the mode of transmission from pigs to humans remains unknown.

PMID- 9621199
TI  - Emergence of the M phenotype of erythromycin-resistant pneumococci in South
      Africa.
AB  - Erythromycin-resistant pneumococci have been isolated in South Africa since 1978;
      however, from 1987 to 1996, resistance to macrolides was only detected in 270
      (2.7%) of 9,868 blood or cerebrospinal fluid (CSF) pneumococcal isolates, most of
      which were obtained from the public sector. In South Africa, macrolide use in the
      public sector is estimated at 56% of that in the private sector. Most
      erythromycin-resistant strains (89%) exhibited resistance to erythromycin and
      clindamycin (macrolide-lincosamide-streptogramin B phenotype). In the United
      States, most erythromycin-resistant pneumococci exhibit the newly described M
      phenotype (resistance to erythromycin alone), associated with the mefE gene. The
      M phenotype in South Africa increased significantly in the last 10 years, from 1
      of 5,115 to 28 of 4,735 of blood and CSF isolates received from 1987 to 1991
      compared with 1992 to 1996 (p = 5 x 10(-7)). These data suggest that, although
      macrolide resistance in pneumococci remains low in the public sector, the mefE
      gene is rapidly emerging in South Africa.

PMID- 9621200
TI  - Mycobacterium tuberculosis infection as a zoonotic disease: transmission between
      humans and elephants.
AB  - Between 1994 and 1996, three elephants from an exotic animal farm in Illinois
      died of pulmonary disease due to Mycobacterium tuberculosis. In October 1996, a
      fourth living elephant was culture-positive for M. tuberculosis. Twenty-two
      handlers at the farm were screened for tuberculosis (TB); eleven had positive
      reactions to intradermal injection with purified protein derivative. One had
      smear-negative, culture-positive active TB. DNA fingerprint comparison by IS6110
      and TBN12 typing showed that the isolates from the four elephants and the handler
      with active TB were the same strain. This investigation indicates transmission of
      M. tuberculosis between humans and elephants.

PMID- 9621201
TI  - New vectors of Rift Valley fever in West Africa.
AB  - After an outbreak of Rift Valley fever in Southern Mauritania in 1987,
      entomologic studies were conducted in a bordering region in Senegal from 1991 to
      1996 to identify the sylvatic vectors of Rift Valley fever virus. The virus was
      isolated from the floodwater mosquitoes Aedes vexans and Ae. ochraceus. In 1974
      and 1983, the virus had been isolated from Ae. dalzieli. Although these vectors
      differ from the main vectors in East and South Africa, they use the same type of
      breeding sites and also feed on cattle and sheep. Although enzootic vectors have
      now been identified in West Africa, the factors causing outbreaks remain unclear.

PMID- 9621202
TI  - Reemergence of Plasmodium vivax malaria in the republic of Korea.
AB  - Plasmodium vivax malaria reemerged in the Republic of Korea in 1993. The number
      of cases has tripled each year since, with more than 1,600 cases reported in
      1997. All 27 cases in U.S. troops resolved uneventfully with
      chloroquine/primaquine therapy. Disease is localized along the western
      Demilitarized Zone and presents minimal risk to tourists.

PMID- 9621203
TI  - Molecular and epidemiologic analysis of dengue virus isolates from Somalia.
AB  - Nucleotide sequence analysis was performed on 14 dengue virus isolates (13 dengue
      2 viruses and 1 dengue-3 virus) recovered from febrile soldiers in Somalia in
      1993. The dengue-2 viruses were most closely related to dengue-2 virus recovered
      in Somalia in 1984. However, differences in nucleotide sequence (0.35% to 1.35%)
      were evident among the 1993 isolates. These differences were closely associated
      with the geographic location of the infection as well as with different times of
      infection at the same location. Genetic difference between strains was not
      associated with differences in clinical features. Molecular analysis of dengue
      viruses is a useful adjunct to epidemiologic investigation of their distribution
      over distance and time.

PMID- 9621204
TI  - Molecular characterization of a novel Rickettsia species from Ixodes scapularis
      in Texas.
AB  - A novel Rickettsia species of undetermined pathogenicity was detected in Ixodes
      scapularis. DNA sequencing showed the highest nucleotide sequence similarities
      with R. australis for the 17 kDa gene, R. helvetica for gltA, and R. montana for
      rompA. The new organism, provisionally designated as genotype Cooleyi, is highly
      divergent in three conserved genes from recognized Rickettsia species.

PMID- 9621205
TI  - Dual infection with Ehrlichia chaffeensis and a spotted fever group rickettsia: a
      case report.
AB  - Well-documented cases of simultaneous human infection with more than one tick
      borne pathogen are rare. To our knowledge only two dual infections have been
      reported: simultaneous human infection with the agent of human granulocytic
      ehrlichiosis and Borrelia burgdorferi and simultaneous human infection with B.
      burgdorferi and Babesia microti (1-2). Rocky Mountain spotted fever has long been
      known to be endemic in North Carolina; cases of human ehrlichial infection were
      recognized there soon after Ehrlichia chaffeensis was recognized as an important
      cause of tick-borne disease in the southeastern United States. Because both Rocky
      Mountain spotted fever and ehrlichiosis are prevalent in North Carolina,
      occasional cases of simultaneous human infection by rickettsial and ehrlichial
      agents would not be surprising; however, no such cases seem to have been
      reported.

PMID- 9621206
TI  - Molecular fingerprinting of multidrug-resistant Salmonella enterica serotype
      Typhi.
AB  - For epidemiologic investigations, the primary subdivision of Salmonella Typhi is
      vi-phage typing; 106 Vi-phage types are defined. For multidrug-resistant strains
      the most common types have been M1 (Pakistan) and E1 (India, Pakistan,
      Bangladesh, and the Arabian Gulf); a strain untypable with the Vi phages has been
      responsible for a major epidemic in Tajikistan. Most often, isolates from the
      Indian subcontinent have been resistant to ampicillin, chloramphenicol,
      streptomycin, sulfonamides, tetracyclines, and trimethoprim; but in the 1997
      Tajikistan outbreak, the epidemic strain was also resistant to ciprofloxacin. For
      multidrug-resistant strains, subdivision within phage type can be achieved by
      plasmid profile typing and pulsed-field gel electrophoresis.

PMID- 9621207
TI  - Clostridium septicum infection and hemolytic uremic syndrome.
AB  - Five cases of Clostridium septicum infection secondary to Escherichia coli O157
      induced hemolytic uremic syndrome have been reported. We report on three cases
      (one of which is included in the above five) of dual Cl. septicum and E. coil
      infection; all three patients were exposed to farm animals. A common zoonotic
      source for Cl. septicum and E. coli O157 infections should be considered.
      Patients with hemolytic uremic syndrome should be treated aggressively and
      monitored closely for Cl. septicum superinfection.

PMID- 9621208
TI  - Persistent infection of pets within a household with three Bartonella species.
AB  - We monitored by blood culture and immunofluorescence assay (IFA) bartonella
      infection in one dog and eight cats in a household to determine the prevalence
      and persistence of the infection as well as its transmissibility to humans.
      Ectoparasite control was rigorously exercised. During a 3-year period, Bartonella
      clarridgeiae was recovered from one cat on two occasions, and B. henselae was
      isolated from another cat on four occasions. During a 16-month period, B.
      vinsonii subsp. berkhoffii was isolated from the dog on 8 of 10 culture attempts.
      Despite extensive household contact, the pet owner was seronegative to all three
      species by IFA for Bartonella-specific immunoglobulin G.

PMID- 9621209
TI  - Using nurse hot line calls for disease surveillance.
AB  - Nurse hot line calls are a potential source of public health surveillance data
      and may help identify epidemics of emerging infectious diseases. In this study,
      nurse hot line data from Milwaukee, Wisconsin, showed more than a 17-fold
      increase in calls for diarrhea during the 1993 Milwaukee cryptosporidiosis
      outbreak. Moreover, consistent patterns of seasonal variation in diarrhea- and
      vomiting-related calls were detected from the Baltimore, Maryland, and
      Albuquerque, New Mexico, hot lines. Analysis of nurse hot line calls may provide
      an inexpensive and timely method for improving disease surveillance.

PMID- 9621210
TI  - Vector-borne disease surveillance and natural disasters.

PMID- 9621211
TI  - Similarity of chemokines charge and the V3 domain of HIV-1 env protein.

PMID- 9621213
TI  - Forging new perspectives on disease surveillance.

PMID- 9621212
TI  - Detection of glycoprotein of Burkholderia pseudomallei.

PMID- 9621214
TI  - Provide a context for disease emergence.

PMID- 9621215
TI  - Resistance to dryness of Escherichia coli O157:H7 strains from outbreak in Sakai
      City, Japan, 1996.

PMID- 9621216
TI  - Irradiation pasteurization of solid foods.

PMID- 9621217
TI  - Emerging infectious diseases in Brazil.

PMID- 9621218
TI  - A brief update on rabbit hemorrhagic disease virus.

PMID- 9621219
TI  - Rabbit hemorrhagic disease.

PMID- 9621220
TI  - The national food safety initiative.

PMID- 9621221
TI  - Effects of milk somatic cell count on cottage cheese yield and quality.
AB  - Eight Holstein cows in midlactation were selected for low milk somatic cell count
      (SCC) and the absence of the pathogens that cause mastitis. Milk collection and
      cottage cheese manufacture from low SCC milk were replicated on each of 4 d
      (control period). Each cow was infused with 1000 cfu of Streptococcus agalactiae.
      One week after infusion, milk from the same eight cows was collected and
      commingled. On each of 4 d, cottage cheese was made from milk with high SCC
      (treatment period). A mass-balance protocol, accounting for protein and total
      solids, was used to determine recoveries in whey, wash water, and uncreamed curd.
      Actual yields, yields adjusted for composition, and theoretical yields of
      uncreamed curd were calculated. Mean milk SCC for the periods with the low SCC
      (control) and the high SCC (treatment) were 83 x 10(3) and 872 x 10(3) cells/ml,
      respectively. The recovery of protein in the uncreamed curd was higher during the
      low SCC period than during the high SCC period (75.85% vs. 74.35%). High SCC and
      the associated higher proteolytic activity caused higher protein loss in the whey
      and wash water and more curd fines. The percentage of total solids recovery in
      uncreamed curd was higher for high SCC milk because the lactose content of the
      high SCC milk was 0.27% lower than that of the low SCC milk. The moisture content
      of the curd was higher for the high SCC milk (82.75% vs. 83.81%). Proteolysis
      during refrigerated storage was faster in cottage cheese made from high SCC milk.
      The yield efficiency of uncreamed curd, adjusted for composition based on 81%
      moisture, was 4.34% lower for the cottage cheese curd made from high SCC milk.

PMID- 9621222
TI  - Influence of salt on the quality of reduced fat cheddar cheese.
AB  - Cream was homogenized in a two-stage homogenizer (17.25 MPa in the first stage
      and 3.43 MPa in the second stage); blended with skim milk to produce milk
      containing 1.25% fat, which was pasteurized (63 degrees C for 30 min); and then
      manufactured into reduced fat Cheddar cheese. After milling, the curd was divided
      into three equal portions of 13 kg each. Three salting rates, 2.3, 3.8, and 5%,
      yielded cheeses with 1.3, 1.7, and 2.0% salt and 2.7, 3.7, and 4.5% salt in the
      moisture phase. Cheese moisture contents ranged from 45% (2.0% salt) to 47.7%
      (1.3% salt), and fat contents ranged from 14.6 to 15.1%. In the texture profile
      analysis, the hardness and fracturability of the cheeses increased as the salt
      content increased. Both parameters decreased during ripening, but cheeses with
      4.5% salt in the moisture phase remained the hardest. Cheeses with the most salt
      had the least desirable body characteristics, but there were no differences in
      flavor. Intensity of bitterness was lowered as the amount of salt in cheese
      increased. During ripening, the number of lactic acid bacteria decreased more
      slowly in cheese with 2.7% salt in the moisture phase than in those with 3.7 or
      4.5% salt in the moisture phase. As the salt content increased, proteolysis and
      the general rate of ripening decreased. Degradation of alpha s-casein was reduced
      by higher percentages of salt, but no differences were found in the degradation
      of beta-casein.

PMID- 9621223
TI  - Sensory and physical properties of ice creams containing milk fat or fat
      replacers.
AB  - The purpose of this research was to determine the relative effects of milk fat,
      nonfat milk solids, or each of three whey protein type fat replacers on the
      flavor and texture attributes of vanillin-flavored ice cream. Descriptive sensory
      analyses disclosed that ice creams containing 4.8% of any of the fat replacers in
      place of milk fat had no demonstrable effect on vanillin flavor but increased the
      intensities of whey flavor, syrup flavor, and cooked milk flavor. Compared with
      each substitute, milk fat significantly reduced the syrup, whey, and cooked milk
      flavors and increased the fresh milk and cream flavors of the ice cream. Results
      emphasized the importance of fat as a flavor modifier and the importance of
      certain fat replacers as aids in improving texture.

PMID- 9621224
TI  - Cell-free whey from milk fermented with Bifidobacterium breve C50 used to modify
      the colonic microflora of healthy subjects.
AB  - The ingestion of viable bacteria is thought to be required to modify intestinal
      microflora. In the present study, the effects on fecal flora of consumption of
      cell-free concentrated whey from milk that had been fermented with
      Bifidobacterium breve C50 was tested using 10 healthy human volunteers. Results
      were compared with effects of a commercial milk formula that had been fermented
      with Streptococcus thermophilus and B. breve C50 and given to 10 control
      subjects. Nitroreductase and beta-glucuronidase activities were assessed as risk
      indexes for colon carcinogenesis, and beta-galactosidase was measured as an
      indicator of the fermentation capacity of the colonic flora. Fecal excretion of
      Bacteroides fragilis, Clostridium perfringens, and clostridial spores decreased
      after 7 d of consumption of either preparation; however, counts of bifidobacteria
      only increased after intake of B. breve whey. Fecal pH was reduced from 7.1 +/-
      0.2 to 6.6 +/- 0.3 after intake of whey that had been fermented with Bif. breve.
      Fecal nitroreductase and beta-glucuronidase significantly decreased, and beta
      galactosidase activity increased, after consumption of either preparation. The
      results indicate that ingestion of viable bifidobacteria was not required to
      modify intestinal flora of humans. Repression of B. fragilis and clostridia seems
      to be independent of colonic bifidobacterial overgrowth in humans.

PMID- 9621225
TI  - Characteristics of the estrous cycle and antioxidant status of lactating Holstein
      cows exposed to heat stress.
AB  - Follicular growth, lifespan of the corpus luteum, and antioxidant status of
      lactating Holsteins that experienced heat stress were monitored. Eleven
      multiparous cows, 60 to 110 d in milk, were maintained from 0800 to 1800 h daily
      in environmental chambers from d 11 to 21 of the estrous cycle. Cows were
      randomly assigned to a heat stress (mean dry bulb temperature peaked at 38.3
      degrees C) or control treatment (mean dry bulb temperatures varied from 20.8 to
      25.6 degrees C). Rectal temperature and respiration rates of heat-stressed cows
      were higher at 1600 h than were those of control cows. The length of the estrous
      cycle and the interval from estrus until luteolysis were not different between
      treatments. Two of 6 control cows and 1 of 5 heat-stressed cows had extended
      cycles (> 24 d). Heat-stressed cows had more class 1 (2 to 5 mm) follicles from d
      11 to 15 of the estrous cycle. Numbers of class 2 (6 to 9 mm) and class 3 (> or =
      9 mm) follicles were similar between treatments. Plasma progesterone
      concentrations were higher for heat-stressed cows until d 19 of the estrous
      cycle. Treatment did not affect concentrations of alpha-tocopherol, beta
      carotene, retinol, retinyl palmitate, or total protein in plasma or
      concentrations of malondialdehyde in muscle. In conclusion, heat stress did not
      extend luteal function or the length of the estrous cycle of lactating Holstein
      cows but did affect follicular growth and progesterone concentrations in plasma.
      Heat stress did not appear to increase lipid peroxidation or decrease lipid
      soluble antioxidant concentrations in blood.

PMID- 9621226
TI  - Trans-octadecenoic acids and milk fat depression in lactating dairy cows.
AB  - We examined the role of trans-octadecenoic acids in milk fat depression when low
      fiber diets were fed. The study consisted of four experimental periods with a 2 x
      2 factorial arrangement of treatments to test the effects of dietary fat
      (saturated vs. unsaturated) and rumen fermentation (high fiber diets vs. low
      fiber diets) on milk fat depression. Dietary fiber concentration and type of fat
      had significant effects on milk fat. Effects were most pronounced when
      unsaturated fat was added to the low fiber diet. When the low fiber diet plus
      unsaturated fat was fed, milk fat percentage and yield were decreased by 30 and
      35%, respectively, compared with the percentage and yield when the high fiber
      diet plus saturated fat was fed. Alterations in rumen fermentation caused by
      differences in dietary fiber concentrations had little effect on the amount of
      trans-octadecenoic acids in milk fat, and the total amount did not correlate with
      changes in milk fat percentage. Further examination of the isomeric profile of
      trans-octadecenoic acid revealed substantial differences among the dietary
      treatments. Although the addition of unsaturated fat resulted in marked increases
      in the milk fat content of trans-11-octadecenoic acid, regardless of dietary
      fiber concentration, the low fiber diet plus unsaturated fat increased the
      content of trans-10-octadecenoic acid. This combination was also associated with
      a significant decrease in milk fat content and yield. When the low fiber diets
      were fed, circulating insulin concentrations were elevated, regardless of the
      type of fat supplement. However, marked milk fat depression occurred only when
      the low fiber diet was supplemented with unsaturated fat.

PMID- 9621227
TI  - Effect of the use of bovine somatotropin on culling practices in thirty-two dairy
      herds in Indiana, Michigan, and Ohio.
AB  - Data from 5468 Holstein dairy cows in 32 herds were used to determine the effect
      of the use of bovine somatotropin (bST) on culling practices over a 13-mo period.
      After an initial herd inventory, monthly information regarding cow entry and exit
      from the herds was obtained by seven participating veterinarians. Culling was
      coded by farmers for the following reasons: low production, reproduction, somatic
      cell count, mastitis, sickness, dairy purposes, lameness, death, and other. In
      the control herds, cows were not treated with bST during the trial. Adopter herds
      were defined as herds that utilized supplemental bST for > or = 25% of the cow
      days during the trial. Mean herd use of bST in adopter herds was 38.6%. No
      difference in the number of cows culled per cow-day at risk was detected between
      control and adopter herds (0.09 and 0.11%, respectively). Amount of in-herd use
      of bST was unrelated to culling. No significant differences were determined
      between adopter and control herds in the percentage of cows that were culled for
      any of the nine possible culling reasons. The results of this study suggest that
      culling patterns in herds that use bST are unaffected for at least the first year
      after adoption.

PMID- 9621228
TI  - Inhibition of in vitro growth of coliform bacteria by a monoclonal antibody
      directed against ferric enterobactin receptor FepA.
AB  - The ability of a murine monoclonal antibody that blocks the enterobactin ligand
      binding site of the ferric enterobactin receptor FepA to inhibit the growth of
      coliform bacteria derived from a bovine intramammary infection (IMI) was
      determined in an iron-restricted medium. Bacterial isolates from bovine IMI in
      five herds were tested by the chrome azurol sulfonate assay to detect siderophore
      production. Each of the isolates of Escherichia coli (n = 25) and Klebsiella
      pneumoniae (n = 25) were positive for siderophore production. Each isolate
      expressed iron-regulated outer membrane proteins when grown in trypticase soy
      broth plus the iron chelator alpha-alpha'-dipyridyl. Immunoblots revealed that
      the monoclonal antibody recognized FepA that was expressed by each of the E. coli
      isolates (n = 25). Only 4 of 25 K. pneumoniae isolates produced FepA that reacted
      with the monoclonal antibody. This result coincided with the results of an in
      vitro growth assay. Growth of all E. coli isolates was significantly inhibited by
      the addition of monoclonal antibody to synthetic medium containing
      apolactoferrin. Antigenic variation in the enterobactin-binding site resulted in
      a low percentage of K. pneumoniae isolates that were inhibited by the monoclonal
      antibody. Inhibition of bacterial growth by the monoclonal antibody was dose
      dependent. As little as 50 micrograms/ml of purified antibody had an inhibitory
      effect on bacterial growth in the synthetic iron-restricted medium. Monoclonal
      antibody specific for the enterobactin ligand-binding site of FepA inhibited the
      growth of E. coli that was isolated from bovine IMI.

PMID- 9621229
TI  - Identification of risk factors for clinical mastitis in dairy heifers.
AB  - A nested case-control study was conducted to identify risk factors for clinical
      mastitis in heifers. Cases and controls originated from dairy herds that were
      enrolled in the Production Recording Scheme. Heifers that had been treated for
      clinical mastitis prepartum or on the day of parturition were eligible for
      inclusion as cases. The controls were heifers that had not been treated for
      clinical mastitis before parturition, during their first lactation, or during the
      dry period. In the final analysis, 4256 heifers with mastitis and 67,072 control
      heifers were included. An increase in the incidence of clinical mastitis in the
      herd, a decrease in the bulk milk somatic cell count, and an increase in the mean
      milk yield of the herd were associated with an increased risk for clinical
      mastitis. The risk varied among regions, and, depending on region, significant
      influences of both herd size and composition of the diet were observed. Heifers
      kept on pasture in summer were at a decreased risk for clinical mastitis. Calving
      in late spring or summer was associated with greater risk than was calving at
      other times of the year. An increase in age at first calving was associated with
      increased risk of mastitis. Mastitis was also more likely to occur in heifers
      leaking milk or in heifers that had a low milk flow rate in the subsequent
      lactation. For purchased heifers, risk factors were identified in both their
      previous and current herds.

PMID- 9621230
TI  - Influence of clinical mastitis during early lactation on reproductive performance
      of Jersey cows.
AB  - The purpose of this study was to determine the influence of clinical mastitis on
      reproductive performance of high producing Jersey cows. Cows (n = 102) with
      clinical mastitis during the first 150 d of lactation were evaluated. Groups were
      balanced according to lactation number and days of lactation and sub-divided as
      follows: group 1, clinical mastitis before first artificial insemination (AI) (n
      = 48); group 2, clinical mastitis between first AI and pregnancy (n = 14); group
      3, clinical mastitis after confirmed pregnancy (n = 40); and group 4, control
      cows (n = 103) with no clinical mastitis. No differences in reproductive
      performance were detected because of milk production or mastitis caused by Gram
      positive or Gram-negative pathogens. The number of days to first AI was
      significantly greater for cows with clinical mastitis before first AI (93.6 d)
      than for all other groups (71.0 d). Artificial inseminations per conception were
      significantly greater for cows with clinical mastitis after first AI (2.9) than
      for cows with clinical mastitis before first AI (1.6), cows with no clinical
      mastitis, or cows with clinical mastitis after confirmed pregnancy (1.7). The
      number of days to conception for cows with clinical mastitis after first AI
      (136.6 d) was significantly greater than that for control cows and that for cows
      that developed clinical mastitis after confirmed pregnancy (92.1 d). Clinical
      mastitis during early lactation markedly influenced reproductive performance of
      Jersey cows.

PMID- 9621231
TI  - Effects of mastitis on the volume and composition of colostrum produced by
      Holstein cows.
AB  - The effects of mastitis during the late nonlactating period on colostral volume
      and concentrations and total yields of immunoglobulin (Ig) G1, fat, and protein
      in colostrum were investigated using matched pairs of mammary glands from
      multiparous Holstein cows. Samples of mammary secretions were collected at
      approximately 14 and 7 d prepartum and within 3 h after calving. At each sampling
      time, the glands and secretions were examined for gross abnormalities, and the
      California Mastitis Test was performed. Duplicate secretion samples from each
      gland were cultured, and somatic cell count, pH, and fat and protein
      concentrations were determined. The volume of colostrum obtained at the first
      milking of each gland was quantified using a quarter milking device, and its IgG1
      concentration was measured. Colostral volume from persistently infected mammary
      glands was lower than that from matched uninfected glands, as was the total mass
      of IgG1. However, infection did not alter IgG1 concentration in colostrum. Fat
      and protein percentages were lower in prepartum secretions but not in colostrum
      from infected glands. Persistent infection was associated with increased somatic
      cell count and pH of secretions at all sampling times, and California Mastitis
      Test scores were higher for colostrum from infected glands. The appearance of
      secretions was extremely variable, but the presence of flakes or clots in
      colostrum was associated with infection. We concluded that mastitis during the
      late nonlactating period alters mammary gland function but is unlikely to be an
      important contributor to the high rate of failure of passive transfer of
      immunoglobulins in calves.

PMID- 9621232
TI  - Parameters of test day milk yield and milk components for dairy ewes.
AB  - A total of 3119 test day records for milk yield, somatic cell count (SCC), and
      contents of fat, protein, casein, serum protein, lactose, and total solids were
      obtained weekly from 155 lactations of Churra ewes during both the suckling and
      milking periods. All of the variables were significantly affected by stage of
      lactation, number of live lambs weaned, age at parity, and parity number within
      age. The lactation curves for SCC and for percentages of protein, casein, fat,
      and total solids were related inversely to the lactation curves for milk yield
      and lactose percentage. The SCC curve reached its lowest point at wk 5, which
      coincided with the maximum milk yield. At wk 3, lactose content reached its peak,
      and contents of fat, protein, casein, and total solids reached their lowest
      points. After weaning, monthly within-lactation correlations of the variables
      were simulated; values were 0.584 for yield, 0.468 for SCC, 0.371 for casein
      percentage, 0.360 for total solids percentage, 0.350 for protein percentage,
      0.342 for fat percentage, 0.270 for lactose percentage, and 0.030 for serum
      protein percentage. Simplified procedures based on only one milking (a.m. or
      p.m.) could be effective in the testing programs for milk yield and SCC, thus,
      reducing the economic costs of milk recordings in mammary health and breeding
      programs.

PMID- 9621233
TI  - Estimation of plasma volume in Holstein and Jersey calves.
AB  - The concentration of immunoglobulin (Ig) G in the blood of neonatal calves
      shortly after birth is a widely used criterion to determine the degree of
      acquisition of passive immunity. Another method used to determine the biological
      mechanisms of IgG absorption is calculation of the apparent efficiency of IgG
      absorption. Estimation of the efficiency of IgG absorption requires the
      estimation of plasma volume in neonatal calves. Previous estimates of plasma
      volume in a few calves of varying breeds have been made; the estimates ranged
      from 7 to 14.5% of body weight (BW). Holstein (n = 97 from four farms) and Jersey
      (n = 49 from one farm) calves were fed fresh maternal colostrum or colostrum that
      had been previously frozen. Calves were fed 2 L of colostrum at 4.1 h (SE = 0.2;
      range = 0.3 to 11.0 h) and 12 h later. Plasma volume was measured by determining
      the concentration of Evans' blue dye in a jugular blood sample collected 10 min
      after injection of approximately 1.5 ml of 1.5% Evans' blue dye. Factors that
      affected plasma volume (milliliters) were BW, breed, and age at sampling; r2 of
      the regression was 0.60. Factors that affected plasma volume (percentage of BW)
      were BW, breed, and age at sampling; r2 of the regression was 0.08. Mean plasma
      volume for all calves was 3162 ml (SE = 79) and was 9.86% of birth BW (SE =
      0.15%). Mean plasma volume was 2250 ml (9.71% of BW) and 3623 ml (9.94% of BW)
      for Jersey and Holstein calves, respectively. Body weight was the best predictor
      of plasma volume.

PMID- 9621234
TI  - Comparison of the kinetics of pancreatic secretion and gut regulatory peptides in
      the plasma of preruminant calves fed milk or soybean protein.
AB  - Exocrine secretion from the pancreas and concentrations of cholecystokinin,
      gastrin, secretin, and somatostatin in plasma were measured in relation to
      feeding in 70- to 120-d-old preruminant calves fed either a milk diet or a
      soybean diet. Pancreatic fluid was continuously collected, measured, and
      reintroduced in catheterized calves. Blood samples were withdrawn for
      measurements of gut regulatory peptide concentrations in plasma. A slight
      increase in outflow of pancreatic fluid was observed 30 min before the milk diet
      was introduced but not before the soybean diet was fed. In contrast,
      concentrations and outflows of protein and trypsin immediately after feeding were
      higher when calves were fed the soybean diet. Overall, during the first 5 h
      postfeeding, the outflow of pancreatic fluid was 40% higher when the milk diet
      was fed than when the soybean diet was fed. No difference in outflow of protein
      was observed, but that of trypsin was 82% higher when the soybean diet was fed.
      This enhanced enzyme secretion could have been related to the increased plasma
      concentrations of gastrin and cholecystokinin after the soybean diet was fed.
      Secretin release was less in calves fed the milk diet that in calves fed the
      soybean diet during the first 2 h postfeeding, suggesting that this gut peptide
      along with gastrin and cholecystokinin, contributed to the stimulation of enzyme
      secretion. Plasma gut regulatory peptides could be influenced by the soybean
      diet, which does not coagulate in the stomach, inducing faster gastric emptying
      of protein and fat, and by the chemical form of protein from the soybean diet and
      the lower susceptibility of these proteins to protease compared with casein.
      However, the resulting enhancement of pancreatic trypsin secretion and activity
      seemed to be insufficient to increase the digestibility of soybean protein up to
      a level similar to that of milk.

PMID- 9621235
TI  - The effect of preservatives based on propionic acid on the fermentation and
      aerobic stability of corn silage and a total mixed ration.
AB  - For 3 successive yr, whole-plant corn was ensiled in laboratory silos with low
      percentages of silage preservatives, the primary active ingredient of which was
      propionic acid. Preservatives were added to forage just prior to ensiling at
      rates of 0.1 to 0.2% of the fresh forage weight. In all 3 yr, treatments had
      minor effects on fermentation end products, except that the concentration of
      propionic acid was greater because of its addition. The mean low and high
      percentages of preservatives increased aerobic stability of the treated silages
      by 19 and 57 h, respectively, in Experiment 1 and by 17 and 38 h, respectively,
      in Experiment 2. In Experiment 3, aerobic stability was improved by > 90 h by
      preservatives (0.2% addition). In a lactation study, a total mixed ration (46%
      dry matter) was mixed without or with (0.2 or 0.3%) a stabilizer that was
      designed to prevent spoilage in the feed bunk. The high dose resulted in orts
      with a lower pH and temperature after 24 h in the feed bunk. However, dry matter
      intake and milk production were unaffected by treatments. Chemical preservatives
      based on propionic acid added at low rates did not affect fermentation but were
      effective in the reduction of heating in corn silage and in a total mixed ration.

PMID- 9621236
TI  - Proportions of volatile fatty acids in relation to the chemical composition of
      feeds based on grass silage.
AB  - This experiment was designed to quantify the relationships between feed chemistry
      and the proportions of rumen volatile fatty acids (VFA) across a wide range of
      feedstuffs. In an experiment using 11 rumencannulated sheep, 16 test feeds were
      fed at three different inclusion rates in rations that were based on grass
      silage. The 17 periods of the experiment were each 14 d long. Eight rumen samples
      were taken every 24 h on d 13 and 14 of each period from which the mean daily
      proportions of VFA were derived. The effects of an increase in the proportion of
      test feed in the total feed on proportions of VFA were significant. The observed
      proportions of VFA were related to the chemical composition of the total feed by
      principal component regression. The inclusion of the amount of feed offered and
      the ratio of test feed to total feed in these regressions did not improve their
      precision; these terms were not significant. The significant terms in the
      regressions were crude protein, starch, sugar, and cellulose (calculated by
      difference). The R2 values achieved for the regressions between acetate,
      propionate, and butyrate (molar proportions) and feed composition were 77.5,
      68.0, and 87.3%, respectively. These regressions provided an apparently robust
      basis for predicting molar proportions of VFA from feed chemistry in feeds based
      on grass silage.

PMID- 9621237
TI  - Effect of yeast on feed intake and performance of cows fed diets based on corn
      silage during early lactation.
AB  - Thirty-six multiparous Holstein cows were fed a mixture of corn silage and
      concentrate [1:1; dry matter (DM) basis] and long hay (0.9 kg/d) through wk 18 of
      lactation. Beginning at 30 d prepartum through wk 4 of lactation, the total mixed
      rations of 18 of these cows were top-dressed daily with 10 g of Biomate Yeast
      Plus (Chr. Hansen's, Inc., Milwaukee, WI). The other 18 cows served as controls.
      At wk 5, both control and treated cows were divided into three groups and fed 0,
      10, or 20 g/d of yeast. Yeast supplementation during early lactation
      significantly improved DM intake, milk yield, and the digestibility of crude
      protein and acid detergent fiber. Least squares means for DM intake, fat
      corrected milk yield, crude protein digestibility, and acid detergent fiber
      digestibility for cows fed 0, 10, 20 g/d of yeast during wk 5 to 18 of lactation
      were 23.8, 24.7, and 25.0 kg/d; 37.7, 40.7, and 41.4 kg/d; 78.5, 80.8, and 79.5%;
      and 54.4, 60.2, and 56.8%, respectively. Although numerical responses in DM
      intake and milk yield were greater for cows fed 20 g/d of yeast than for cows fed
      10 g/d of yeast, the response was not significant.

PMID- 9621238
TI  - Increase in milk yield of commercial dairy herds fed a microbial and enzyme
      supplement.
AB  - A microbial and enzyme supplement fed at 21.2 g/d per cow to 46 Virginia dairy
      herds increased the milk yield of 31 herds (17 significantly) and decreased the
      milk yield of 15 herds (7 significantly). Effects of season were important but
      consistent with overall results. Herds began receiving the supplement, which
      contained dried fermentation products of Aspergillus oryzae, Bacillus subtilis,
      Lactobacillus acidophilus, and yeast culture, midway between the first and second
      monthly Dairy Herd Improvement tests and continued on the supplement through the
      3rd mo. Entry of herds was staggered over 8 mo to reduce the influence of season.
      The trial involved 3417 cows with 5 test mo between 60 and 365 d in milk. Milk
      yield during mo 3 averaged 0.64 kg/d per cow more (+0.73 kg/d for first lactation
      cows and +0.56 kg/d for later lactation cows) than the mean milk yield during mo
      1 and 5. Herds completing the study before summer responded similarly to all
      other herds, which included herds that were fed the product during summer and
      those that finished the study during summer. Fat and protein yields and protein
      percentage differed little with or without the supplement. Fat percentage
      decreased (0.10%). Twenty-one herds that were fed a yeast product prior to and
      during the study responded similarly to the 17 herds that were not fed a yeast
      product.

PMID- 9621239
TI  - Effect of a mixture of feather and blood meals on lactational performance of
      dairy cows.
AB  - An experiment was conducted over 18 wk of lactation to determine the effect of
      supplemental feather and blood meals (85:15, wt/wt, dry matter basis) fed at two
      dietary concentrations of crude protein (CP) on dry matter intake and milk
      protein production. Forty-eight Holstein cows were grouped by parity and assigned
      randomly at 3 wk postpartum to one of four diets following a 2-wk covariate
      period. Diets consisted of 50% alfalfa silage and 1) no feather or blood meals,
      17.6% CP, and 5.1% ruminally undegradable protein (RUP); 2) 4% mixture of feather
      and blood meals, 17.6% CP, and 6.3% RUP; 3) no feather or blood meals, 19.6% CP,
      and 6.3% RUP; and 4) 4% mixture of feather and blood meals, 19.6% CP, and 6.9%
      RUP. According to the National Research Council, diet 1 was deficient in RUP,
      diets 2 and 3 were adequate in RUP, and diet 4 contained excessive CP and RUP.
      Intakes of dry matter and CP were depressed by 11% for cows fed the 19.6% CP diet
      supplemented with feather and blood meals. For cows fed the 17.6% CP diet, the
      supplementation of feather and blood meals increased RUP intake, but the
      supplementation of feather and blood meals to the 19.6% CP diet had no effect on
      RUP intake. Supplemental feather and blood meals increased the production of milk
      protein and 3.5% solids-corrected milk by cows fed the 17.6% CP diet. Diets 2, 3,
      and 4 resulted in similar efficiencies of solids-corrected milk production, but
      the efficiency of milk protein production specifically was increased by the
      supplementation of feather and blood meals to the 17.6% CP diet only. Results of
      this experiment indicate that a mixture of feather and blood meals improves the
      production of milk protein when supplemented to a diet that meets, but does not
      greatly exceed, the requirements established by the National Research Council for
      RUP and that contains alfalfa as the sole forage.

PMID- 9621240
TI  - Ruminally protected lysine or lysine and methionine for lactating dairy cows fed
      a ration designed to meet requirements for microbial and postruminal protein.
AB  - The purpose of this study was to separate the effects of ruminally protected Lys
      from effects of ruminally protected Met on the performance of lactating dairy
      cows fed a ration calculated to be first-limiting in intestinally delivered Lys
      and second-limiting in intestinally delivered Met. Thirty multiparous Holstein
      cows were examined in a 20-wk study that started on wk 5 postpartum. Rations
      contained timothy silage, corn silage, barley, corn, corn gluten meal, and
      soybean meal. Treatments were 1) no supplemental amino acids, 2) 21 g/d of
      intestinally available Lys, and 3) 22 g/d of intestinally available Lys and 6 g/d
      of intestinally available Met. Post-experimental calculations suggested that, in
      contrast to the objective, the unsupplemented ration was colimiting in
      intestinally available His (0.96 of requirement), followed by Lys (1.00),
      digestible ruminally undegraded protein (1.01), Ile (1.03), Arg (1.04), Val
      (1.10), and Met (1.14). In this context, the virtually identical performance of
      cows fed the unsupplemented ration and cows fed the ration supplemented with
      ruminally protected Lys demonstrated that dairy cows did not respond to enhanced
      intestinal supplies of Lys when Lys was not calculated to be the first-limiting
      nutrient. In contrast, for cows fed rations supplemented with both ruminally
      protected Lys and ruminally protected Met, the production of both milk protein
      (40 g/d) and fat (40 g/d) was numerically increased to an extent that was
      consistent with earlier reported studies, although calculations did not indicate
      that performance was limited by intestinal supplies of Lys or Met. This result,
      which may be disputed because of a lack of statistical significance, suggests
      that Met, apparently unlike Lys, may enhance the production of milk components
      beyond an enhancement expected because of its role as a limiting amino acid.

PMID- 9621241
TI  - Protein degradability and calcium salts of long-chain fatty acids in the diets of
      lactating dairy cows: productive responses.
AB  - Our objective was to evaluate the effect of excessive intake of ruminally
      degradable crude protein [11.1 and 15.7% of dietary dry matter (DM)] and
      supplemental fat (Ca salts of long-chain fatty acids at 0 or 2.2% of dietary DM)
      on the productive performance of lactating Holstein cows (n = 45) during the
      first 120 d postpartum. The main N sources were soybean meal and urea in the
      diets with high concentrations of degradable protein versus a combination of
      vegetable and animal by-product feedstuffs in the diets with less degradable
      protein. Cows fed the diets with excess degradable protein had slower rates of
      increase in DM intake (DMI) and milk production, had lower plasma insulin and
      greater plasma glucose and urea concentrations, and lost more than twice the body
      weight of cows fed the diets with less degradable protein. Supplemental fat in
      the highly degradable protein diet reduced the loss of body condition, stimulated
      DMI, and reduced concentrations of plasma nonesterified fatty acids early
      postpartum compared with the highly degradable protein diet without added fat.
      Without affecting DMI, supplemental fat stimulated milk production (2 kg/d)
      starting at 3 wk postpartum. During early lactation, DMI and milk production were
      sensitive to the degree of ruminal degradability of protein and energy
      supplementation in the form of fat.

PMID- 9621242
TI  - Protein degradability and calcium salts of long-chain fatty acids in the diets of
      lactating dairy cows: reproductive responses.
AB  - Multiparous Holstein cows (n = 45) were assigned at calving to one of four diets
      arranged in a 2 x 2 factorial design. The two main factors were dietary
      concentration (dry matter basis) of 1) degradable intake protein (11.1 or 15.7%)
      and 2) supplemental fat (Ca salts of long-chain fatty acids; 0 or 2.2%). Soybean
      meal and urea were replaced with less degradable protein meals (corn gluten meal,
      meat and bone meal, fish meal, and blood meal). During the first 9 wk postpartum,
      cows fed diets containing the greater concentration of highly degradable protein
      demonstrated less follicular development on their ovaries, were delayed in their
      first luteal activity postpartum (25.2 vs. 38.6 d), accumulated less luteal
      tissue (< 15 vs. > 70 mm), and had lower plasma progesterone accumulated over
      time. The supplementation of Ca salts of long-chain fatty acids to the 15.7%
      degradable protein diet doubled the number of corpora lutea, reduced time to
      first rise in progesterone by 6 d, doubled the number of normal luteal phases,
      and restored the pattern of accumulated plasma progesterone concentrations to a
      pattern that was similar to that induced by other diets. Cows were synchronized
      to estrus and inseminated at approximately 65 d postpartum. Pregnancy rate was
      increased from 52.3 to 86.4% when fat was supplemented. Cows fed fat tended to
      have more corpora lutea and a larger corpus luteum and accumulated more plasma
      progesterone than did cows not fed fat. Diets containing excess degradable
      protein or Ca salts of long-chain fatty acids influenced ovarian structures and
      reproductive performance.

PMID- 9621243
TI  - Interactions of tallow and hay particle size on yield and composition of milk
      from lactating Holstein cows.
AB  - An 18-wk lactation study was conducted to determine whether the effects of tallow
      on the lactation performance of dairy cows were influenced by particle size of
      hay in the ration. A total mixed ration containing 50% concentrate, 25% corn
      silage, and 25% alfalfa hay (dry matter basis) was fed to Holstein cows. Four
      total mixed rations were developed based on differences in the percentage of
      tallow in the concentrate and particle size of alfalfa hay: 1) 0% tallow, long
      cut hay; 2) 0% tallow, short-cut hay; 3) 5% tallow, long-cut hay; and 4) 5%
      tallow, short-cut hay. Ration had no effect on dry matter intake, body weight
      gain or change in body condition score. Tallow increased milk and milk protein
      yields but reduced milk protein concentration. However, the effects of tallow on
      milk and milk protein yields were the same, regardless of hay length in the
      ration. A tendency for an interaction of tallow and hay particle size was
      detected for fat-corrected milk (FCM) because tallow increased FCM more when hay
      was short. Ration had no effect on volatile fatty acids in ruminal samples
      collected via a stomach tube. In this study, the effects of tallow on milk yield
      and composition from Holstein cows were the same, regardless of hay particle size
      in the ration. The tendency for tallow to increase FCM more when hay was short
      suggests at least a limited role of forage particle size in the determination of
      how fat supplements in dairy rations affect lactation performance.

PMID- 9621244
TI  - Performance and nutrient intake of high producing Holstein cows consuming pasture
      or a total mixed ration.
AB  - We compared the intakes of nutrients by high producing Holstein cows consuming
      pasture or a full nutrient positive control ration (total mixed ration; TMR) and
      identified nutrients that limited the milk production of cows consuming the high
      quality pasture. Cows (n = 8) were adapted to an all pasture diet by
      incrementally reducing the amount of TMR fed over a 4-wk period. A control group
      of cows (n = 8) remained in confinement and was fed a TMR. The performance of
      grazing cows differed significantly from that of cows fed the TMR in dry matter
      (DM) intake (19.0 vs. 23.4 kg/d of DM), milk production (29.6 vs. 44.1 kg/d),
      milk protein content (2.61% vs. 2.80%), live weight (562 vs. 597 kg), and body
      condition score (2.0 vs. 2.5). The high quality of the pasture permitted cows to
      consume the same daily intakes of neutral detergent fiber and crude protein
      (kilograms per day) as cows fed the TMR, but the pasture provided 19% less DM,
      organic matter, and net energy for lactation. Predictions using National Research
      Council estimates and the Cornell Net Carbohydrate and Protein System model
      indicated that the supply of metabolizable energy was first-limiting for the milk
      production of cows consuming high quality pasture rather than the supply of
      metabolizable protein or amino acids. Although a daily intake of 19 kg of DM was
      achieved on spring pasture, the significant mobilization of energy reserves
      indicated that supplemental energy is required to achieve milk production greater
      than 30 kg/d from high producing Holstein cows on intensive grazing systems.

PMID- 9621245
TI  - Dietary supplements of folic acid during lactation: effects on the performance of
      dairy cows.
AB  - The present experiment was undertaken to determine the effects of dietary
      supplements of folic acid administered from 4 wk prepartum to 305 d of lactation
      on lactational performance. Sixty-three Holstein cows were assigned to 22 blocks
      of 3 cows according to lactation number, milk production, and body weight (BW).
      Within each block, cows received 0, 2, or 4 mg of folic acid/kg of BW per d.
      Dietary supplements of folic acid increased serum and milk folates but affected
      milk production and composition of primiparous and multiparous cows differently.
      Supplementary folic acid had little effect on milk production and composition of
      primiparous cows, except that milk production decreased during the first 100 d of
      lactation. However, during a complete lactation (3 to 305 d after calving),
      supplementary folic acid was associated with increased milk production by
      multiparous cows (8284 +/- 560, 8548 +/- 380, and 8953 +/- 191 kg for cows fed
      diets supplemented with 0, 2, and 4 mg of folic acid/kg of BW per d,
      respectively). The percentage of ash in milk was decreased for cows fed the
      highest amount of dietary folic acid. During the first 100 d of lactation,
      supplementary folic acid was associated with a lower concentration of nonprotein
      nitrogen in the milk of multiparous cows. The present study confirms results
      obtained previously, suggesting that, although the supply of folates from an
      unsupplemented diet and the ruminal microflora is sufficient to avoid a
      deficiency in folic acid, supplementary folic acid may increase the milk
      production of cows in the second lactation or greater.

PMID- 9621246
TI  - The effect of enhanced milk yield of dairy cows by frequent milking or suckling
      on intake and digestibility of the diet.
AB  - Groups of 9 or 10 cows were assigned to one of three treatments 1) machine
      milking three times daily, 2) machine-milking six times daily, and 3) suckling
      three times daily in addition to machine-milking three times daily. Treatments
      were conducted during the first 6 wk postpartum. During wk 5, digestibility of
      the diet was estimated by the indigestible neutral detergent fiber method. During
      wk 6, milk yield and dry matter intake (DMI) were recorded daily, and plasma
      concentrations of glucose, nonesterified fatty acids, urea, protein, growth
      hormone, insulin, insulin-like growth factor I, oxytocin, and prolactin were
      determined. Milk yields were 38.5, 46.8, and 52.7 kg/d, and DMI were 18.1, 21.2,
      and 17.2, for cows on treatments 1, 2, and 3, respectively. Plasma glucose
      concentrations decreased, and plasma nonesterified fatty acid concentrations
      increased, for cows on treatments 2 and 3 compared with cows on treatment 1.
      Digestibility of dry matter was 57.5, 60.5, and 60.6%; of organic matter was
      62.6, 64.6, and 66.8%; and of crude protein was 59.3, 62.7, and 64.6% for cows on
      treatments 1, 2, and 3, respectively. Concentrations of all assayed hormones,
      except insulin, increased moderately for cows on treatment 2 compared with cows
      on treatment 1 and increased dramatically for cows on treatment 3. Insulin
      concentrations followed the opposite trend. The DMI were positively related to
      milk yields and negatively related to oxytocin concentrations. Digestibility was
      negatively related to plasma glucose concentrations in a nonlinear pattern. The
      possible involvement of hormones in improvement of digestibility is discussed.

PMID- 9621247
TI  - Generalized linear mixed models in dairy cattle breeding.
AB  - Fitness and fertility traits of dairy cattle are of increasing importance and are
      often measured on a discrete scale. The development and application of
      generalized linear mixed models to the genetic analysis of these traits are
      reviewed. Because current genetic evaluation systems are predominantly based on
      animal models, the inferential challenges of highly parameterized generalized
      linear mixed models are discussed. Development and adoption of new methods for
      drawing appropriate inferences on dispersion parameters are essential. Recent
      hierarchical extensions have been proposed for generalized linear mixed models,
      allowing for complex dispersion patterns that accommodate heteroscedasticity and
      outlier robustness. Steady advances in available computing power have facilitated
      multiple-trait analyses involving continuous and discrete measures. Full Bayesian
      inference via the development of Markov Chain Monte Carlo methods will continue
      to allow even greater generality and dimensions in the genetic model.

PMID- 9621248
TI  - Genetic correlations among somatic cell scores, productive life, and type traits
      from the United States and udder health measures from Denmark and Sweden.
AB  - Sire genetic evaluations for protein yield, somatic cell score (SCS), productive
      life, and udder type traits from the US were correlated with sire evaluations for
      udder health from Denmark and Sweden and then the correlations were adjusted for
      accuracies to approximate genetic correlations. Traits from Denmark and Sweden
      included somatic cell count (SCC) and clinical mastitis from single-trait
      analyses. In addition, evaluations for clinical mastitis from Denmark and Sweden
      were regressed on US traits to test for quadratic relationships. Information from
      85 bulls with US and Danish evaluations (77 with US type) and from 80 bulls with
      US and Swedish evaluations (79 with US type) was used to calculate correlations.
      Genetic correlations of US protein yield with Danish and Swedish SCC and clinical
      mastitis were all unfavorable (-0.09 to -0.32). Genetic correlations of US
      productive life with Danish and Swedish SCC and clinical mastitis were all
      favorable (0.06 to 0.59). Genetic correlations between US SCS and Danish SCC and
      between US SCS and Swedish SCC were -0.87 and -0.99, respectively (favorable).
      Genetic correlations between US SCS and Danish clinical mastitis and between US
      SCS and Swedish clinical mastitis were -0.66 and -0.49, respectively (favorable).
      The US type traits that had the largest correlations with clinical mastitis from
      Denmark and Sweden, respectively, were udder composite (0.26, 0.47), udder depth
      (0.45, 0.52), and fore udder attachment (0.31, 0.34). In general, quadratic
      regressions indicated little nonlinearity between clinical mastitis and the US
      traits. Specifically, the US bulls with the lowest predicted transmitting
      abilities for SCS had the most favorable rates of daughter clinical mastitis in
      Denmark and Sweden. Selection for increased productive life, lower SCS, and more
      shallow udders should improve mastitis resistance.

PMID- 9621249
TI  - Mapping of serum amylase-1 and quantitative trait loci for milk production traits
      to cattle chromosome 4.
AB  - The present study was undertaken to confirm and refine the mapping of a
      quantitative trait locus in cattle for milk fat percentage that had earlier been
      reported to be linked to the serum amylase-1 locus, AM1. Five half-sib families
      from the previous study and 7 new ones were genotyped for nine microsatellite
      markers spanning chromosome 4. AM1 was mapped between the microsatellite markers
      BMS648 and BR6303. In a granddaughter design, interval mapping based on multiple
      marker regression was utilized for an analysis of five milk production traits:
      milk yield, fat percentage and yield, and protein percentage and yield. In the
      families reported on previously, significant effects for fat and protein
      percentages were detected. In the new families, an effect on milk and fat yields
      was found. The most likely positions of the quantitative trait locus in both
      groups of families were in the same area of chromosome 4 in the vicinity of the
      obese locus. Direct effects of the obese locus were tested for using polymorphism
      in two closely linked microsatellites located 2.5 and 3.6 top downstream of the
      coding sequence. No firm evidence was found for an association between the obese
      locus and the tested traits.

PMID- 9621250
TI  - Haplotype construction of sires with progeny genotypes based on an exact
      likelihood.
AB  - A maximum likelihood method is presented that can be used to construct parental
      haplotypes based on their progeny genotypes. The exact error rate and choice of
      family size in haplotype construction were evaluated through mathematical
      expressions and numerical examples. Numerical results suggest that, if two
      markers are tightly linked (< or = 10 cM) and each has intermediate allele
      frequencies, a difference of one between progeny receiving parental and
      recombinant gametes is sufficient for constructing sire linkage phase; a
      difference of two or more progeny is required with two markers 30 cM apart. When
      each of two adjacent markers has two alleles with equal allelic frequencies,
      genotyping 10 and 50 progeny are needed to achieve a power of 0.85 for
      constructing a sire linkage phase of two tightly (10 cM) and moderately tightly
      linked (30 cM) markers, respectively. The family size is reduced by approximately
      half when both markers have three alleles with equal frequencies. Results suggest
      that, when an experiment requiring haplotype determination of a parent is being
      designed, researches should choose the appropriate threshold and family size in
      the context of marker allelic frequencies and recombination fractions.

PMID- 9621251
TI  - Bayesian analysis of Wood's lactation curve for Spanish dairy cows.
AB  - A Bayesian procedure is presented to analyze test day performances in the scope
      of Wood's lactation function: atb (exp (-ct)), where a, b, and c = parameters,
      and t = time-dependent variable. The procedure has been applied to 148,557 test
      day controls corresponding to records for 15,349 first lactations of Spanish
      dairy cows. The procedure uses all available information and reduces the presence
      of atypical lactations. Moreover, the posterior marginal distribution of
      (co)variance components, breeding values, and systematic effects for the
      underlying variables of Wood's function are provided. The posterior means of the
      heritabilities were 0.43, 0.17, 0.40, and 0.29 for the parameters a (initial milk
      yield), b (ascent to peak), c (descent from peak), and total milk yield,
      respectively. Selection for total milk yield implies a great effect on the
      initial milk yield (a) but only minor effects on ascent to peak (b) and descent
      from peak (c).

PMID- 9621253
TI  - Ethical issues in stem cell transplantation.

PMID- 9621252
TI  - Relative efficiencies of wither height and body weight increase from birth until
      first calving in Holstein cattle.
AB  - Female Holstein calves from the Purina Research Center herd averaged 74 cm of
      height at withers and 40 kg of body weight (BW) at birth. At first calving (24 mo
      of age), calves averaged 138 cm of height at withers, 611 kg at precalving BW,
      and 547 kg at postcalving BW. Fifty percent of the total height increase occurred
      from birth to 6 mo of age, 25% occurred during 7 to 12 mo of age, and 25%
      occurred during 13 to 24 mo of age. Twenty-five percent of the total BW increase
      occurred from birth to 6 mo of age, 25% occurred from 6 to 12 mo of age, and the
      remaining 50% occurred from 13 to 24 mo of age. The increase in BW for 2-mo
      intervals, expressed as a proportion of the BW of the previous 2-mo interval,
      declined most rapidly during the first 6 mo, intermediately during the second 6
      mo, and more slowly and progressively during the final 12 mo. Feed cost per unit
      of BW gain was lowest during the first 6 mo and then increased at a decreasing
      rate over the final 18 mo. The proportion of BW to height linearly increased over
      the 24-mo period. The increase in wither height as a proportion of the wither
      height during the previous period was greatest during the first 6 mo,
      intermediate during the second 6 mo, and lowest in the final 12 mo. Feed cost per
      unit of height increase was lowest in the first 6 mo, intermediate during the
      second 6 mo, and highest with a rapid increase during the final 12 mo. The
      increases in relative BW and wither height are the most rapid and cost efficient
      during the first 6 mo of life.

PMID- 9621254
TI  - A closed culture system for the ex vivo transduction and expansion of human T
      lymphocytes.
AB  - A phase I clinical trial is currently being performed at our institution, with
      the aim of evaluating the feasibility and toxicity related to the administration
      of herpes simplex thymidine kinase gene-expressing human primary T lymphocytes
      following allogeneic hematopoietic stem cell transplantation. The need for safe
      and standardized preparation conditions for gene-modified cells is crucial. We
      describe the closed culture system used in the current trial for ex vivo
      retroviral-mediated gene transfer and transduced cell selection. Cell handling is
      performed in closed systems using a sterile connection device that avoids opening
      the culture system. Cell numbers during the production process increased from 93
      +/- 16 on day 0 to 440 +/- 92 x 10(6) on day 12 (7.2 +/- 1.4-fold increase) (n =
      11). Transduction efficiency before and after G418 resistance-based selection was
      13.5 +/- 3.8% and 90.0 +/- 1.4%, respectively. Safety and efficacy testing
      included a search for replication-competent retrovirus, endotoxins, Mycoplasma,
      and bacterial contamination (n = 0/9), PCR-DNA, % CD3+ cells (91 +/- 2%), and
      viability after thawing (82 +/- 3%). Effective working time from day 0 to day 12
      is approximately 20 h. The closed system we developed allows for safe and
      reproducible ex vivo preparation of gene-modified primary T lymphocytes for
      clinical use.

PMID- 9621255
TI  - Increased transduction efficiency of primary hematopoietic cells by physical
      colocalization of retrovirus and target cells.
AB  - Efficient gene transfer into hematopoietic stem cells offers a number of
      potential therapeutic applications. However, the relatively low titer of
      retroviral supernatants and the requirement for cell division to ensure
      integration have meant that transduction efficiency has been low. We have
      modified a flowthrough approach to cell transduction and have been able
      consistently to increase gene transfer efficiency into human hematopoietic
      progenitor cells. We transduced CD34 cells with retroviral vectors encoding a
      truncated nerve growth factor receptor (NGFR) or neo. Retroviral supernatant was
      pulled through 0.2-micron polycarbonated membranes, followed by placement of
      cells on the filter. In the absence of cytokines, the transduction efficiency of
      CD34 cells with a NGFR vector was increased 3-11-fold over that obtained at an
      identical MOI in liquid culture to produce 11%-44% transduction. Furthermore,
      both Thy1+ and Thy1- subsets in a total CD34 population were transduced with
      similar efficiency, and transduction with a neo vector, as measured by G418
      resistance in clonogenic assays, increased 1.5-5-fold. The mechanism by which
      gene transfer is improved may reflect colocalization of cells and retrovirus.
      Costaining of cells transduced on the filter with an NGFR retrovirus with both an
      NGFR antibody and a gp70 antibody that recognizes viral coat protein revealed
      high-level coexpression. The levels of in vitro gene transfer we obtain are
      equivalent to those observed when CD34 cells are cocultured in liquid culture
      with cytokines. However, culture with cytokines may commit CD34 cells to
      differentiation and has produced disappointingly low levels of subsequent in vivo
      gene transfer. Gene marking studies using distinguishable retroviral vectors will
      provide a means of learning whether the effects of flowthrough transduction
      genuinely enhance the efficiency of gene transfer to human marrow-repopulating
      cells.

PMID- 9621256
TI  - Retroviral-mediated marker gene transfer in hematopoiesis-supportive marrow
      stromal cells.
AB  - A Moloney-derived retrovirus containing both LacZ and NeoR genes (G1BgSVNa from
      Genetic Therapy, Inc.), was used to transduce human and murine bone marrow
      stromal cells. Different kinds of stromal cells that were able to support
      hematopoiesis were transduced by incubation for 24 h in the presence of virus
      containing supernatant. Semiconfluent layers of MRC-5 (human, myofibroblastic,
      fetal, pulmonary) and MS-5 (murine, myofibroblastic, medullary) cells were
      successfully transduced after one 24-h incubation, as demonstrated by G418
      resistance and Escherichia coli beta-galactosidase staining. In contrast, human
      stromal cells, purified from primary confluent layers grown for 3-4 weeks, could
      not be transduced. However, stromal cells generated after 10-12 days in culture
      from Stro-1+ and 1B10+ stromal precursors were successfully transduced in the
      presence of basic fibroblast growth factor. Transduced stromal cells maintained a
      myofibroblastic phenotype, although with a decreased number of alpha-SM actin
      positive microfilaments in MS-5 cells. The ability to support the generation of
      stroma-adherent colony-forming cells from cocultured cord blood CD34+ cells after
      4 weeks in culture was similar before and after transduction and G418 selection.
      In conclusion, human primary stromal precursors can be efficiently transduced,
      and the stromal cell phenotype and function are not significantly altered after
      retroviral-mediated transfer of marker genes.

PMID- 9621258
TI  - Distribution of mobilized progenitor cells in the buffy coat of the haemonetics
      MCS3p cell separator: a study to optimize the collection of progenitors by
      leukapheresis.
AB  - Hematopoietic progenitor and stem cells for transplantation can be mobilized into
      the circulation and collected by leukapheresis. In this procedure, the leukocytes
      are distributed in the buffy coat along a density gradient, and the composition
      of the final product depends on which layer was collected. For the Haemonetics
      MCS3p Cell Separator, the manufacturer recommended starting the progenitor cell
      collection at a light transmission of 30%-40% (compared with plasma) and continue
      it for 40-50 ml. To optimize the use of this machine, the buffy coat it produces
      was studied in 12 patients by collecting it in fractions of increasing specific
      weight. Each fraction was analyzed by morphology, immunocytometry, and cell
      culture. We found that the buffy coat uniformly contains 8 times more leukocytes
      than blood, but the proportion of each white cell type varies along a gradient.
      The lymphocyte-predominant lighter layers are richer in CD34+ cells when compared
      with the granulocyte-predominant denser layers (6-14 times versus 2-4 times more
      than blood). The majority of CD34+ cells are found at a light transmission of 10%
      70% (hematocrit 6-9). We conclude that cells for transplantation should be
      collected in a lighter fraction of the buffy coat than originally suggested by
      the manufacturer.

PMID- 9621257
TI  - Second attempts at mobilization of peripheral blood stem cells in patients with
      initial low CD34+ cell yields.
AB  - The purpose of this study was to determine the effectiveness of second
      mobilization strategies in patients who yielded < 2.5 x 10(6) CD34+ PBSC/kg after
      initial mobilization. Repeat mobilization attempts were made with chemotherapy
      and G-CSF (n = 61) or G-CSF alone (n = 58) in patients who failed initial
      mobilization with chemotherapy and G-CSF (n = 92) or G-CSF alone (n = 27). A
      median of 0.27 x 10(6) CD34+ cells/kg per apheresis was collected after the
      second mobilization, compared with 0.16 with initial harvests (p = 0.0001). Forty
      eight percent achieved a target CD34+ cell dose > or = 2.5 x 10(6)/kg when
      harvests from the first and second mobilizations were combined. Fifteen of 17
      patients (88%) with > or = 1.5 x 10(6) CD34+ cells/kg harvested after first
      mobilization had > or = 2.5 x 10(6) CD34+ cells/kg collected when first and
      second harvests were combined, as compared with 42 of 102 (41%) achieving < 1.5 x
      10(6) CD34+ cells/kg with first PBSC harvests (p = 0.0001). Second mobilizations
      with chemotherapy and G-CSF or G-CSF alone resulted in similar CD34+ cell yields.
      Toxicities of second mobilizations were comparable with those of first
      mobilizations. Seventy-nine patients (66%) received high-dose chemotherapy with
      PBSC support, with recovery of neutrophils and platelets in a median of 11 and 15
      days, respectively. Transplant-related mortality was 4%, and event-free survival
      at 2 years was 0.34. It was concluded that second mobilization attempts in
      patients who fail to achieve > or = 2.5 x 10(6) CD34+ cells/kg on initial
      mobilization were successful in 48% of patients. G-CSF alone was as effective as
      chemotherapy plus G-CSF in mobilizing CD34+ cells and was associated with less
      morbidity.

PMID- 9621259
TI  - Feasibility of cellular adoptive immunotherapy for Epstein-Barr virus-associated
      lymphomas using haploidentical donors.
AB  - Epstein-Barr virus (EBV)-associated lymphomas following bone marrow or solid
      organ transplantation are often sensitive to immunomodulatory therapies. These
      have included withdrawal or reduction in immunosuppressive therapy in the solid
      organ transplant setting and adoptive cellular therapies in the bone marrow
      transplant (BMT) setting. We describe a strategy for generating EBV-specific
      cytotoxic T cell therapy lines with substantial killing activity against
      haploidentical targets. Weekly stimulation of peripheral blood mononuclear cells
      (PBMCs) for 3 weeks with the irradiated cells of an autologous EBV-transformed B
      lymphoblastoid cell line (B-LCL), followed by stimulation in the presence of IL
      2, yielded T cell lines that were cytolytic for haploidentical B-LCLs but did not
      lyse haploidentical targets not expressing EBV antigens.

PMID- 9621260
TI  - A family with Leber's hereditary optic neuropathy with mitochondrial DNA
      heteroplasmy related to disease expression.
AB  - A Japanese family has members with Leber's hereditary optic neuropathy resulting
      from the heteroplasmic 11778 mutation and the homoplasmic 4216 mutation.
      Quantitative determination of heteroplasmy was performed by a combination of
      polymerase chain reaction and single-strand conformation polymorphism analysis.
      The association between heteroplasmy and clinical features was determined. Eleven
      people from the maternal side of the family, including four affected and seven
      unaffected members, showed heteroplasmy of the mtDNA mutation ranging from 5% to
      more than 95%. Four possibly affected patients had more than 90% of the mutant
      mtDNA. Seven unaffected people had mutant mtDNA ranging from 5% to 77%. A
      recovery episode of visual acuity was noted in the history of three of the four
      patients. Heteroplasmy is likely to be a factor in the expression of disease in
      this family.

PMID- 9621261
TI  - Energy charge is not decreased in lymphocytes of patients with Leber's hereditary
      optic neuropathy with the 11,778 mutation.
AB  - OBJECTIVES: A defect in mitochondrial energy conservation is strongly suggested
      to be involved in the pathogenesis of Leber's hereditary optic neuropathy (LHON).
      The authors therefore compared the energy charge in lymphocytes among patients
      with LHON, their asymptomatic maternal lineages, and normal control subjects.
      MATERIALS AND METHODS: Blood samples were obtained from 7 patients, 10
      asymptomatic maternal relatives, and 16 normal subjects. Molecular analysis
      confirmed that all had the homoplasmic 11,778 point mutation in the mtDNA of
      their blood cells. The concentrations of adenosine triphosphate (ATP),
      diphosphate (ADP), and monophosphate (AMP) were determined by high-performance
      liquid chromatography. The energy charge was calculated as (ATP + 1/2 ADP)/(ATP +
      ADP + AMP). RESULTS: The mean energy charges of lymphocytes were 0.871 +/- 0.049
      in patients with LHON, 0.884 +/- 0.061 in their asymptomatic maternal relatives,
      and 0.885 +/- 0.061 in normal controls, respectively. No statistically
      significant difference was found among the three groups. CONCLUSIONS: Although
      the study did not find the anticipated change in energy charge in peripheral
      blood cells, this neither confirms nor rejects the notion that a defect in the
      mitochondrial oxidative phosphorylation system is involved in the pathogenesis of
      LHON.

PMID- 9621262
TI  - Neuro-ophthalmology of the pregeniculate afferent visual system. May, 1997
      November, 1997 (Part II).

PMID- 9621263
TI  - Childhood sarcoidosis.
AB  - A 10-year-old black girl exhibited a bilateral lower motor neuron facial palsy
      and bilateral hearing loss. Gadolinium-enhanced magnetic resonance imaging of the
      brain showed enhancement of the cranial nerve VII-VIII complex bilaterally. Disc
      elevation developed in both eyes, and the patient exhibited facial swelling.
      Examination of a right parotid biopsy specimen demonstrated noncaseating
      granulomas, consistent with the diagnosis of sarcoidosis.

PMID- 9621264
TI  - Pituitary adenoma in children.
AB  - Pituitary adenoma is an uncommon intracranial tumor of children. The authors
      retrospectively reviewed the records of 10 patients younger than 17 years of age
      with pituitary adenoma. Five patients had visual loss at presentation. Four of
      these five patients with visual loss and extrasellar tumor extension were
      adolescents (12-15 years of age). Seven of 10 patients underwent neurosurgery. Of
      the five patients with visual loss, three patients experienced visual
      improvement, one patient was unchanged, and one patient did not have follow-up.
      The visual loss in these patients tended to be more severe and more likely to be
      associated with optic atrophy than adult patients. Although they are relatively
      uncommon, ophthalmologists should be aware that pituitary adenomas may occur in
      children and that these tumors when present in the pubertal period may be more
      likely to exhibit extrasellar extension or invasiveness.

PMID- 9621265
TI  - Nutritional amblyopia.
AB  - A review was conducted to examine the characteristics and pathogenesis of
      nutritional amblyopia. Published cases of amblyopia among malnourished allied
      prisoners of the Japanese during World War II and among Cubans malnourished
      during the recent economic embargo were analyzed. The picture of nutritional
      amblyopia derived from these publications is somewhat at variance with the
      conventional image of the disease. Surprising features include premonitory
      keratopathy, rapid onset of visual loss, a high incidence of hearing loss, and
      the presence of peripapillary retinopathy in some cases. No single causative
      factor can be identified. Genetic susceptibility rarely, if ever, plays a role.
      Vitamin deficiency may not be important. Protein deficiency, antioxidant
      deficiency, physical labor, and tobacco smoking are likely to contribute to the
      occurrence of amblyopia.

PMID- 9621266
TI  - Two additional scenarios for see-saw nystagmus: achiasma and hemichiasma.
AB  - The discovery of canine achiasma and hemichiasma has been followed by the
      identification of human achiasma (four individuals, to date). See-saw nystagmus
      was present in all cases of achiasma (canine and human) and in one of two cases
      of canine hemichiasma studied. Human infants with see-saw nystagmus should be
      imaged for possible structural abnormalities of the optic chiasm.

PMID- 9621267
TI  - Eight-and-a-half syndrome: one-and-a-half syndrome plus cranial nerve VII palsy.
AB  - Three cases of isolated one-and-a-half syndrome with facial nerve palsy related
      to infarction are presented. Magnetic resonance imaging in cases 1 and 2 was
      unremarkable, whereas magnetic resonance angiography demonstrated
      pathophysiologically significant vertebral basilar disease. Case 3 is unique due
      to its association with giant cell arteritis. Ipsilateral adduction improved to a
      greater extent than abduction in each case, perhaps providing insight into the
      exact localization of these lesions or selective vulnerability of the ocular
      motor structures within the pons. This combination of clinical findings, termed
      the 8-1/2 syndrome (cranial nerve 7 + 1-1/2), allows precise localization, and
      magnetic resonance angiography appears to be the imaging study of choice.

PMID- 9621268
TI  - Preservation of residual vision 2 years after stereotactic radiosurgery for a
      presumed optic nerve sheath meningioma.
AB  - We performed stereotactic radiosurgery on a patient with a presumed optic nerve
      sheath meningioma with a progressive optic neuropathy and an intact peripheral
      visual field. The patient's visual acuity and visual field have remained stable
      for 2 years following treatment, and the appearance of the tumor has not changed
      by neuroimaging. We believe that stereotactic radiosurgery is a viable option for
      treating optic nerve sheath meningioma.

PMID- 9621269
TI  - Unilateral optic disc edema following trabeculectomy.
AB  - Two cases of a benign form of optic disc edema after successful trabeculectomy
      are reported. In both patients, optic disc edema was noted 2 to 4 weeks after
      trabeculectomy. The edema occurred without loss of visual acuity or field. The
      absolute intraocular pressure and intracranial pressure were normal--that is, the
      edema was not a syndrome of hypotony or pseudotumor cerebri. However, both
      patients had intracranial pressure in the high-normal range. The decrease in
      intraocular pressure into the low normal range after trabeculectomy may have
      altered the intracranial pressure:intraocular pressure ratio at the lamina
      cribrosa enough to produce optic disc edema.

PMID- 9621270
TI  - Postural vision loss in giant cell arteritis.
AB  - Two patients with biopsy-proven giant cell arteritis experienced bilateral
      transient vision loss after bending over and after getting up from a supine
      position. One patient had no demonstrable signs of carotid, ophthalmic, or
      anterior ciliary vascular disease, suggesting that his episodes of transient
      vision loss were due to vertebrobasilar insufficiency. The other patient
      experienced bilateral postural vision loss in the context of impending bilateral
      anterior ischemic optic neuropathy. Bilateral transient postural vision loss is
      an uncommon manifestation of giant cell arteritis that could reflect either
      severe bilateral vascular compromise of the anterior circulation or severe
      vertebrobasilar insufficiency. In either situation, prompt evaluation and
      treatment is indicated to prevent the irreversible sequelae of the disease.

PMID- 9621271
TI  - Annual review of systemic disease--1997--II.
AB  - The intention of this series of semiannual reviews of systemic diseases is not to
      develop an annual encyclopedic compendium of every article published in the prior
      calendar year on each systemic illness but rather to select for each issue a few
      systemic diseases of import to the neuro-ophthalmologist, and to summarize the
      literature that has developed over the past few years. For each systemic disease
      selected, the review will cover new developments in its epidemiology; new reports
      of its neuro-ophthalmic, ocular, and neurologic manifestations; unique clinical
      presentations; radiologic and laboratory diagnostic tools; and new therapies
      available to the neuro-ophthalmologist. If appropriate, new information on the
      etiology of the illness will be reported. In this installment, progress in the
      clinical recognition and treatment of tuberculosis, sarcoidosis, and human
      immunodeficiency virus- (nonretinal) related illness is discussed.

PMID- 9621272
TI  - Asymptomatic autonomic and sweat dysfunction in patients with Adie's syndrome.
AB  - A study was conducted to determine by using noninvasive tests whether autonomic
      dysfunction occurs in patients with Adie's syndrome. Eighteen consecutive
      patients with Aide's syndrome prospectively underwent a standardized battery of
      five noninvasive tests of autonomic function, including three that predominantly
      reflected parasympathetic function and two that predominantly reflected
      sympathetic function. Eight of these patients additionally underwent
      thermoregulatory sweat testing. Of the 18 patients 10 (56%) had no abnormal
      autonomic test results, 5 (28%) had one abnormal result, 2 (11%) had two abnormal
      results, and 1 (6%) had three abnormal results. None of the patients had more
      than three abnormal results. Tests that predominantly reflected parasympathetic
      function produced abnormal results more frequently than those that predominantly
      reflected sympathetic function. Three of eight (38%) patients who underwent
      thermoregulatory sweat testing showed abnormal patterns of sweating. Although
      abnormal autonomic and sweat functions are not uncommon in patients with Aide's
      syndrome, the abnormalities are mild and are generally unassociated with symptoms
      of dysautonomia. Such abnormalities have little clinical significance but may be
      important from a nosologic point of view.

PMID- 9621273
TI  - Terson's syndrome in subarachnoid hemorrhage.

PMID- 9621274
TI  - Lymphomatoid granulomatosis presenting as an isolated unilateral optic
      neuropathy. A clinicopathologic report.
AB  - A 41-year-old woman presented with a unilateral optic neuropathy that progressed
      to no light perception 7 weeks later. The patient was hospitalized for
      progressive dyspnea; respiratory failure ensued and the patient died 10 days
      after admission. Antemortem pulmonary biopsies and the results of necropsy
      revealed lymphomatoid granulomatosis with extensive involvement of the lungs and
      left optic nerve. This is the first case report of lymphomatoid granulomatosis
      presenting as a unilateral optic neuropathy.

PMID- 9621275
TI  - Drug-associated facial dyskinesias--a study of 238 patients.
AB  - The purpose of this study was to determine whether antidepressant, antimania,
      antipsychotic, antihistamine, or antiparkinsonian drugs are associated with
      eyelid and facial dyskinesias; whether discontinuing such drugs results in
      improvement in the facial dyskinesias; and whether response to botulinum toxin
      treatment is influenced by such medications. METHODS: A retrospective review was
      performed on a population of 238 patients with presumed benign essential
      blepharospasm and Meige syndrome. Types of drugs taken before the development of
      disease and clinical response to botulinum toxin injections were studied.
      RESULTS: Fourteen of 238 patients (5.9%) with facial dyskinesias had been
      prescribed a variety of antidepressants, antimania medications, antipsychotics,
      antihistamines, antiparkinsonian drugs, or a combination of these substances
      before their condition developed. The onset of blepharospasm varied from 2 months
      to 35 years after administration of the drug. Three of seven patients who
      discontinued the presumed responsible drug had improvement in their facial
      dyskinesias. Of the 11 patients who did not improve when their drugs were stopped
      or whose medication could not be stopped, all but one patient had a good response
      to treatment with botulinum toxin A. CONCLUSIONS: Drug-induced blepharospasm
      should be considered in all patients who present with facial dyskinesias, and
      such patients should undergo withdrawal of the medication when possible. When
      withdrawal of medication is not possible or does not result in improvement in the
      facial dyskinesia, treatment with botulinum toxin injections should be initiated.
      The possible role in the production of facial dyskinesias of antidepressants that
      block reuptake of serotonin requires further evaluation.

PMID- 9621276
TI  - Increased epithelial cell proliferation and abnormal extracellular matrix in rat
      polycystic kidney disease.
AB  - Proliferation of renal tubular epithelial cells is considered a major factor
      leading to cyst formation in human polycystic kidney disease (PKD). The Han:SPRD
      rat model for inherited PKD permits a close scrutiny, especially for early stages
      of the disease, and shows numerous similarities to human autosomal dominant PKD
      (ADPKD). In this study, the exact in vivo proliferation rate in Han:SPRD rat
      kidneys was evaluated in a cell type-specific manner, using immunohistochemistry
      with antibody to proliferating cell nuclear antigen (PCNA). The proliferation
      index (PI; percentage of PCNA-positive cell nuclei) was determined in normal and
      cystically altered tissue, and a relationship between proliferative activity and
      alterations in extracellular matrix expression was established using in situ
      hybridization for collagen I and IV mRNA. Heterozygously affected rats (cy/+)
      showed strong increases of PI values in cystically altered nephron portions that
      were mostly derived from proximal tubule. Cell proliferation obviously preceded
      cyst formation, because early in the progression of the disease, the normal
      appearing tubules from PKD kidneys had markedly increased PI values compared with
      healthy controls (14.1-fold in 3-mo-old rats and 11.9-fold in 12-mo-old rats; P <
      0.05), whereas later stages revealed a more generalized cystic degeneration of
      the nephron, with increases in PI between 14- and 82-fold, depending on the
      respective category of cystic epithelia. In cysts with a distal phenotype,
      changes were less pronounced. No significant differences were encountered between
      the two age groups. Proliferation was also present in interstitial cells, whereas
      glomeruli were unchanged. Increases in epithelial and interstitial proliferation
      coincided with an overexpression of matrix compounds. For comparison, changes in
      homozygously affected rats (cy/cy) showed up to several hundred-fold elevated PI
      values. These results indicate that in the Han:SPRD model for ADPKD, cystic
      malformation of the nephron is preceded by and coincides with enhanced epithelial
      and interstitial cell proliferation. Altered cell-matrix interactions seem to be
      directly involved in the disruption of epithelial differentiation.

PMID- 9621277
TI  - Immunolocalization and tissue-specific splicing of AE2 anion exchanger in mouse
      kidney.
AB  - In this study, an epitope-unmasking technique was used to immunolocalize AE2
      anion exchanger polypeptide to basolateral plasma membranes of tubular epithelial
      cells in mouse kidney. Kidney AE2 immunostaining in mouse kidney was less
      prominent than in rat, consistent with the relative levels of AE2 mRNA and
      polypeptide in these two species. Glomeruli showed faint but consistent AE2
      immunostaining, whereas proximal tubules were generally unstained. Macula densa
      epithelial cells displayed bright AE2 immunostaining, and cortical thick limbs
      were stained at a lower intensity. AE2 immunostaining was weak or absent in type
      B intercalated cells and principal cells of the cortical collecting duct, but
      increased in intensity in principal cells of the inner stripe of the outer
      medulla. AE2 staining in medullary thick limbs was also of greater intensity than
      in cortical thick limbs. AE2 staining was strong and uniform in the epithelial
      cells of the inner medullary collecting duct, and in epithelial cells of the
      papillary surface, the ureter, and the urinary bladder. Extratubular and
      epithelial cells of the inner medulla also showed punctate intracellular AE2
      staining in a Golgi-like distribution that, in contrast to cell surface staining,
      was sodium dodecyl sulfate-sensitive. Golgi localization of AE2 epitope was
      confirmed by immunoperoxidase electron microscopy. Reverse transcription-PCR
      analysis of mouse kidney RNA detected AE2a, AE2b, and an AE2c2 transcript, but an
      AE2c1 transcript was absent. Unlike in rat, the mouse AE2c2 mRNA splice variant
      encoded a polypeptide with a novel predicted N-terminal amino acid sequence.

PMID- 9621278
TI  - Long-term protein exposure reduces albumin binding and uptake in proximal tubule
      derived opossum kidney cells.
AB  - To avoid renal loss of large amounts of proteins, filtered proteins are
      reabsorbed by endocytosis along the proximal tubule. However, although protein
      reabsorption is a task of proximal tubular cells, it is also a threat because it
      may cause cell injury. This study determines whether exposure to bovine serum
      albumin (BSA) leads to regulatory changes in endocytosis of FITC-BSA in proximal
      tubule-derived opossum kidney cells. Preincubation with BSA led to a decrease of
      FITC-BSA endocytosis with an IC50 value of 0.58 g/L. Specific binding of FITC-BSA
      to the apical membrane was also reduced (IC50 = 0.69 g/L). Kinetic analyses
      revealed that maximal uptake rate and maximal binding capacity were decreased
      with no change in affinity. Similar effects were observed after preincubation
      with equimolar amounts of other proteins (lactalbumin, transferrin, and
      conalbumin), but not after preincubation with dextran. The effect of
      preincubation with BSA could be mimicked by preincubation with some amino acids.
      Preincubation with L-Ala, L-Gln, or NH4Cl, but not with L-Leu, L-Glu, or L-Asp,
      reduced FITC-BSA endocytosis and binding. Preincubation with BSA, but not with
      dextran, reduced protein degradation and increased ammonia production, vesicular
      pH, as well as the rate of lactate dehydrogenase release. Apical fluid-phase
      endocytosis and apical uptake of neutral amino acids were not reduced. It is
      concluded that proximal tubular cells reduce the uptake rate for proteins, but
      not for other substrates, in response to increased protein load. This reduction
      is achieved by reducing the number of apical binding sites, partially in response
      to increased ammoniagenesis with deranged vesicular pH and enzyme activities.
      Thus, increased protein filtration could result in reduced protein reabsorption,
      thereby enhancing proteinuria.

PMID- 9621279
TI  - Effects of angiotensin II on endothelial cell growth: role of AT-1 and AT-2
      receptors.
AB  - Angiotensin II (AngII) is a main mediator in the regulation of vascular tone.
      Although its effects on vascular smooth muscle cells are well known, data on its
      role on endothelial biology are still insufficient. The present study examined
      the effect of endogenous and exogenous AngII on bovine aortic endothelial cells
      possessing both AT-1 and AT-2 receptors. A DNA synthesis-promoting effect of AT-2
      blockade by PD123319 (10(-9) to 10(-7) M) was demonstrated. This effect was
      transduced through an AT-1-mediated pathway, as shown by using the AT-1
      antagonist, losartan. In addition, an AT-1-mediated effect of AngII was
      demonstrated on bovine aortic endothelial cell proliferation, which occurred
      despite the absence of AngII-induced Ca2+ transients. In summary, the present
      study disclosed relevant characteristics of the effect of AngII on endothelial
      cell growth that have potential pathophysiologic projections, particularly for
      the use of selective AngII blocking agents.

PMID- 9621280
TI  - Dopamine regulates phosphate uptake by opossum kidney cells through multiple
      counter-regulatory receptors.
AB  - The purpose of this study was to determine the mechanisms of dopamine regulation
      of phosphate uptake in opossum kidney (OK) cells, a model of proximal renal
      tubules. Dopamine stimulated cAMP generation and inhibited radiolabeled phosphate
      uptake into OK cell monolayers by 14.4 +/- 1.8%. The effect of dopamine was
      transient, as phosphate uptake returned toward control level by 3 h despite the
      continued presence of dopamine. Pretreatment with pertussis toxin increased
      dopamine inhibition of phosphate uptake to 25 +/- 3%, increased the duration of
      the dopamine effect to at least 3 h, and enhanced cAMP generation. In an OK cell
      clone that overexpressed cAMP phosphodiesterase, dopamine did not inhibit
      phosphate uptake, but pharmacologic inhibition of protein kinase A activation did
      not prevent dopamine inhibition of phosphate uptake. A DA1 receptor agonist
      inhibited phosphate uptake more potently than dopamine (29.5 +/- 1.1%) or a DA2
      receptor agonist (7.9 +/- 2%). However, both DA1 and DA2 receptor antagonists
      completely blocked dopamine inhibition of phosphate uptake. DA1, but not the DA2,
      antagonists blocked dopamine-stimulated cAMP generation. Treatment with alpha
      adrenergic receptor antagonists potentiated dopamine inhibition of phosphate
      uptake to the same extent as pertussis toxin and was not additive with pertussis
      toxin. It is concluded that dopamine inhibits phosphate uptake through DA1 and
      DA2 receptor stimulation by cAMP-dependent and -independent pathways and
      activates a pertussis toxin-sensitive counter-regulatory pathway that attenuates
      this response through alpha-adrenergic receptor stimulation.

PMID- 9621281
TI  - The cyclin kinase inhibitor p21WAF1, CIP1 is increased in experimental diabetic
      nephropathy: potential role in glomerular hypertrophy.
AB  - High glucose inhibits mesangial cell proliferation in vitro and induces
      hypertrophy in mesangial cells in culture and in experimental diabetic
      nephropathy. Cell growth is ultimately controlled at the level of the cell cycle
      by cell cycle regulatory proteins. Cell cycle progression requires that cyclin
      dependent kinases be activated by cyclins. Cyclin kinase inhibitors (CKI)
      inactivate cyclin-dependent kinases, causing cell cycle arrest. In the current
      study, high glucose-induced mesangial cell hypertrophy in vitro is shown to be
      associated with increased levels of the CKI p21, but not p27. In the
      streptozotocin model of experimental diabetes in the mouse, glomerular
      hypertrophy was associated with a selective increase in p21 expression, whereas
      the levels of the CKI p27 and p57 did not change. Unlike many other forms of
      glomerular injury, diabetic nephropathy was not associated with increased
      apoptosis. These results support a role for p21 in causing glomerular cell
      hypertrophy in diabetic nephropathy.

PMID- 9621282
TI  - Anti-vitronectin antibodies enhance anti-Thy-1-induced proteinuria in PVG/c, but
      not in Wistar rats.
AB  - Injection of rats with mouse monoclonal IgG2a anti-Thy1.1 antibodies (ER4G)
      results in rapid development of proteinuria in Wistar rats, reaching average
      values of 160 mg/24 h on day 3 after antibody administration. In contrast, no
      overt proteinuria was observed in PVG/c+ rats (maximum, 40 mg/24 h on day 3).
      This study investigates whether differences in the inactivation of C5b-9
      complexes in the glomerulus by complement inhibitors are responsible for the
      differences in proteinuria between the two rat strains. Regardless of the
      presence of proteinuria, an increased expression of Crry by mesangial cells (MC)
      was observed within 24 h after injection of ER4G in both Wistar and PVG/c+ rats.
      Double-label immunofluorescence using goat anti-mouse Ig antibodies demonstrated
      an expression of Crry exclusively on MC. Furthermore, Crry colocalized with C5b-9
      complexes on MC, as detected by a monoclonal antibody against the rat C5b-9 neo
      antigen. In PVG/c+ rats, C5b-9 complexes persisted in the mesangial area for at
      least 7 d and colocalized immediately (within 1 h) and homogeneously with
      vitronectin. However, in proteinuric Wistar rats, C5b-9 complexes disappeared
      from the glomerular mesangium within 6 d. In these rats, mesangial colocalization
      of C5b-9 with vitronectin could only occasionally be detected. Pretreatment of
      PVG/c+ rats with antibodies against vitronectin, followed by administration of
      ER4G, resulted in the immediate development of proteinuria (maximum, 119 mg/24 h
      on day 3; P < 0.05), whereas Wistar rats did not become more proteinuric. This
      study provides evidence that differences in susceptibility of PVG/c+ and Wistar
      rats to complement-mediated damage of the glomerulus may be related to the degree
      of inactivation of C5b-9 complexes by complement regulatory factors.

PMID- 9621283
TI  - Chronic obstructive uropathy in severe combined immunodeficient (SCID) mice:
      lymphocyte infiltration is not required for progressive tubulointerstitial
      injury.
AB  - Progressive renal injury in humans and experimental animal models is
      characterized by tubular atrophy, infiltration of mononuclear inflammatory cells,
      and interstitial fibrosis. Permanent unilateral ureter ligation represents a
      reproducible model for investigating mechanisms of progressive kidney injury, and
      in the rat is characterized by tubular epithelial cell proliferation followed by
      apoptosis and progressive infiltration of monocytes and lymphocytes.
      Nevertheless, whether monocytes or lymphocytes play a dominant role in causing
      tubulointerstitial damage remains to be elucidated. In the current study, a model
      of chronic obstructive uropathy in the mouse is established and the role of
      lymphocyte infiltration in the evolution of the tubule and interstitial
      alterations is investigated. Permanent ligation of the left ureter in wild-type
      (C3H/HeJ) mice resulted in progressive atrophy of tubules and interstitial
      fibrosis compared with the contralateral kidney over a 30-d period.
      Immunoperoxidase studies on frozen sections taken from kidneys at 0, 3, 10, 20,
      and 30 d after ureter ligation showed that the tubulointerstitial injury was
      accompanied by a marked and progressive increase in interstitial macrophages and
      T lymphocytes, with no appreciable increase in B lymphocytes. No increase in
      inflammatory cells was detected in contralateral kidneys over the same time
      frame. The significance of T lymphocyte infiltration was examined by comparing
      the degree of tubular atrophy and interstitial fibrosis and the nature and
      quantity of the inflammatory infiltrate in wild-type mice and C3HSMn.C-Scid/J
      (SCID) mice subjected to permanent left ureter ligation. SCID mice have genetic
      defects in immunoglobulin and T cell receptor gene rearrangements and are devoid
      of circulating mature B and T lymphocytes. Wild-type and SCID mice developed
      tubular atrophy and interstitial volume expansion in the ligated kidney to the
      same degree and at the same rate. SCID mice developed a prominent and marked
      monocyte/macrophage infiltrate in the ligated kidney, which was essentially equal
      to that in wild-type mice. In contrast, consistent with the known absence of
      mature lymphocytes in SCID mice, there was essentially no T lymphocyte
      infiltration into the ligated kidney of SCID mice. These results demonstrate the
      effective establishment of the model of maintained unilateral ureter ligation in
      mice, which is readily applicable to genetic mutant strains thus allowing for
      specific investigation of the role of individual components of the inflammatory
      response in progressive tubulointerstitial injury. These studies further
      demonstrate that lymphocyte infiltration is not required for progressive tubular
      atrophy and increased interstitial fibrosis after maintained unilateral ureter
      ligation.

PMID- 9621284
TI  - Myocyte/capillary mismatch in the heart of uremic patients.
AB  - Experiments indicate that capillary density is reduced in the hypertrophied left
      ventricle of rats with subtotal nephrectomy compared to control rats with similar
      BP and left ventricular hypertrophy, suggesting that in uremia, hypertrophying
      cardiomyocytes outgrow their capillary supply. No information on myocardial
      capillary supply in humans is currently available. The hearts of nine dialyzed
      patients, nine patients with essential hypertension, and 10 normotensive control
      subjects at postmortem were obtained. Subjects with stenosing coronary lesions
      and left ventricular pump failure were excluded. Special sampling procedures were
      used to exclude stereologic artefacts. Capillaries were specifically stained with
      ulex lectin and analyzed by stereologic techniques. Length density of myocardial
      capillaries (Lv; mm/mm3) was significantly (P < 0.001) lower in dialyzed patients
      (1483 +/- 238) than in patients with essential hypertension (1872 +/- 243) or in
      normotensive control patients (2898 +/- 456). In parallel, myocyte diameter and
      volume density of myocardial interstitial tissue were significantly (P < 0.001)
      increased in uremic patients compared to patients with essential hypertension and
      control patients, respectively. Diminished left ventricular capillary supply in
      renal failure must increase critical oxygen diffusion distance in the myocardium,
      thus exposing cardiomyocytes to the risk of hypoxia. It is unknown whether such
      reduced ischemia tolerance can be reversed by increasing oxygen supply (e.g., by
      reversing anemia).

PMID- 9621286
TI  - Receptors of vascular endothelial growth factor/vascular permeability factor
      (VEGF/VPF) in fetal and adult human kidney: localization and [125I]VEGF binding
      sites.
AB  - Vascular endothelial growth factor (VEGF) has an important function in renal
      vascular ontogenesis and is constitutively expressed in podocytes of the adult
      kidney. The ability of VEGF to be chemotactic for monocytes and to increase the
      activity of collagenase and plasminogen activator may have implications for renal
      development and renal disease. In humans, the cellular actions of VEGF depend on
      binding to two specific receptors: Flt-1 and KDR. The aims of this study were:
      (1) to localize VEGF receptor proteins in human renal ontogenesis; (2) to
      quantify VEGF binding in human fetal and adult kidney; and (3) to dissect the
      binding into its two known components: the KDR and Flt-1 receptors. The latter
      aim was achieved by competitive binding of VEGF and placenta growth factor-2,
      which only binds to Flt-1. Quantification of 125I-VEGF binding sites was
      performed by autoradiography and computerized densitometry. By double-label
      immunohistochemistry, VEGF receptor proteins were localized solely to endothelial
      cells of preglomerular vessels, glomeruli, and postglomerular vessels. In
      developing glomeruli, VEGF receptor protein appeared as soon as endothelial cells
      were positive for von Willebrand factor. Specific 125I-VEGF binding could be
      localized to renal arteries and veins, glomeruli, and the tubulointerstitial
      capillary network in different developmental stages. Affinity (Kd) of adult (aK)
      and fetal (fK) kidneys was: Kd: glomeruli 38.6 +/- 11.2 (aK, n = 5), 36.3 +/- 7.1
      (fK, n = 5); cortical tubulointerstitium 19.4 +/- 2.6 (aK, n = 5), 11.6 +/- 7.0
      (fK, n = 5) pmol. Placenta growth factor-2 displaced VEGF binding in all renal
      structures by approximately 60%. VEGF receptor proteins thus were found only in
      renal endothelial cells. A coexpression of both VEGF binding sites could be
      shown, with Flt-1 demonstrating the most abundant VEGF receptor binding sites in
      the kidney. These studies support the hypothesis of a function for VEGF in adult
      kidney that is independent of angiogenesis.

PMID- 9621285
TI  - Ultrastructural and immunohistochemical findings in Alport's syndrome: a study of
      108 patients from 97 Italian families with particular emphasis on COL4A5 gene
      mutation correlations.
AB  - A total of 108 patients affected by Alport's syndrome, taken from 97 families,
      were enrolled in a genetic and ultrastructural study. Sixty-four families (75
      patients) were X-linked, seven autosomal recessive, two autosomal dominant, five
      uninterpretable, and 19 sporadic. The ultrastructural features were consistent
      with Alport's syndrome in 66, doubtful in 20, and not significant for Alport's
      syndrome in 22 patients in the X-linked, sporadic, and genetically
      uninterpretable groups (without significant differences), as well as in the
      autosomal group. Mutations of the COL4A5 gene were present in 36 patients in the
      first three groups, without significant differences. More severe mutations were
      more frequently present in patients with an ultrastructural pattern consistent
      with Alport's syndrome. Nevertheless, there seems to be no strict correlation
      between mutation and ultrastructure, because a major rearrangement was found in a
      patient with no significant lesions, and different morphologic patterns were
      detected in patients Belonging to the same family. Immunohistochemical
      investigation into 24 patients for alpha (IV) chains showed that both alpha 3(IV)
      and alpha 5(IV) were lacking in the glomerular basement membrane of 13 patients
      (five with mutations) and were expressed in another six (three with mutations and
      one in the autosomal group). On the contrary, in this study the retained
      expression of alpha 3(IV) chain was found, despite the lack of alpha 5(IV) in the
      glomerular basement membrane of five patients (two with mutation). These
      different patterns could be related to both the type and severity of the COL4A5
      mutations. All of the ultrastructural patterns were identified in all three
      immunohistochemical groups. Ultrastructural features and alpha 5(IV) chain
      production, even if an expression of a genetic mutation, do not strictly
      correlate. The combined use of analysis of collagen expression and electron
      microscopy made it possible to diagnose Alport's syndrome in 92% of the cohort,
      and therefore this approach is advisable. A multidisciplinary approach is
      recommended in the study of Alport's syndrome in an attempt to achieve a better
      diagnostic definition of and insight into the pathogenetic mechanisms.

PMID- 9621287
TI  - The genetics of renal tumors in end-stage renal failure differs from those
      occurring in the general population.
AB  - The genetics of renal cell tumors (RCT), which occur at a high frequency in
      patients with end-stage renal failure (ESRF), is not yet known. Using a
      fluorescence microsatellite assay and comparative genomic hybridization, 18 renal
      tumors obtained from nine patients with ESRF were analyzed for genetic
      alterations, which are known to be characteristic of common nonpapillary and
      papillary RCT in the general population. Deletion of chromosome 3p was detected
      in six nonpapillary tumors, whereas trisomies of 7 and 17 or 3, 8, and 16 were
      seen in four of 18 tumors. No alterations were found in four tumors, and another
      four tumors had unspecific changes. The fragile histidine triad (FHIT) gene is
      localized at the most common fragile site at chromosome 3p14.2. The FHIT and the
      p53 tumor suppressor gene are targets of different environmental agents. Because
      both toxic effect and genomic instability are implicated in the development of
      renal cysts in ESRF, the alteration of both genes in tumor cells was analyzed. No
      abnormal expression of the FHIT gene or mutation of the p53 gene were found. This
      study suggests that the genetics and also the morphology of some of the ESRF RCT
      differ from those known for RCT in the general population.

PMID- 9621288
TI  - Angiotensin-converting enzyme inhibition reduces the effect of bromoethylamine
      induced papillary necrosis and renal fibrosis.
AB  - Rats injected with a single, 50-mg dose of bromoethylamine (BEA) developed
      papillary necrosis accompanied by sever interstitial fibrosis. At 1 mo, the
      creatinine clearance decreased (control 0.66 versus BEA 0.33 ml/min per 100 g
      body wt, P = 0.02), and the urine albumin-to-creatinine ratio increased markedly
      (control 0.19 versus BEA 0.51, P = 0.02). In a group of animals given the
      angiotensin-converting enzyme inhibitor enalapril (Enal; 100 mg/L) in their
      drinking water for 4 wk, beginning 1 wk before BEA injection, creatinine
      clearance improved significantly (BEA 0.33 versus Enal + BEA 0.52 ml/min per 100
      g body wt, P = 0.01) and albumin excretion fell to zero. Histologic examination
      revealed an 88% decrease in the area of papillary necrosis and a decrease in the
      degree of interstitial fibrosis in the corticomedullary junction. To determine
      whether this was due to changes in urine flow rate induced by enalapril, a group
      of animals was injected with BEA, and enalapril at the above dose was begun 1 wk
      later. After 1 mo, the enalapril-treated animals showed the same improvement in
      creatinine clearance (BEA 0.33 versus BEA + Enal 0.50 ml/min per 100 g body wt, P
      = 0.03) and suppression of albumin excretion. The area of papillary necrosis was
      reduced by 67%. In the BEA animals treated with enalapril, ED-1-positive cells,
      alpha-smooth muscle actin, and transforming growth factor-beta1 were decreased
      compared with BEA alone. It is concluded that in this model of papillary
      necrosis, enalapril protects renal function and decreases interstitial fibrosis
      mediated at least in part through an angiotensin II/bradykinin-dependent
      mechanism.

PMID- 9621289
TI  - Glutathione reverses the growth abnormalities of skin fibroblasts from insulin
      dependent diabetic patients with nephropathy.
AB  - Oxidative stress has been proposed as a possible pathogenic factor for diabetic
      complications. It is relevant in determining cell replicative capacity and life
      span, and in vitro antioxidant treatment is able to reverse the impaired
      proliferative activity of different cell types. It was recently demonstrated that
      cultured skin fibroblasts from insulin-dependent diabetic patients with
      nephropathy age prematurely and have a shorter life cell cycle. To test whether
      the growth phenotype of cells from patients with diabetic nephropathy was related
      to a lack of protection from oxidative stress, the effect of reduced glutathione
      (GSH) on cultured skin fibroblasts from 13 insulin-dependent diabetes mellitus
      (IDDM) patients with nephropathy (DN), 10 IDDM patients without kidney disease
      (D), and 10 nondiabetic control subjects (C), in normal (5 mM) glucose (NG) and
      high (22 mM) glucose (HG) medium was studied. After 6 to 8 passages, fibroblasts
      from DN showed impaired growth both in NG (mean +/- SD fold increase over
      baseline counts in DN 1.17 +/- 0.6 versus D 1.7 +/- 0.5 versus C 1.95 +/- 0.8; P
      = 0.04 by ANOVA) and in HG (mean +/- SD fold increase over baseline counts DN
      1.16 +/- 0.41 versus D 1.89 +/- 0.66 versus C 2.24 +/- 0.9; P = 0.003 by ANOVA).
      GSH prevented the growth abnormalities of cells from DN restoring it to values
      similar to that of the other two groups (mean +/- SD fold increase over baseline
      counts NG +/- GSH: DN 1.68 +/- 0.9 versus D 1.78 +/- 0.49 versus C 1.99 +/- 0.7,
      P = 0.6; and in HG + GSH: DN 1.66 +/- 0.69 versus D 1.87 +/- 0.75 versus C 2.2 +/
      0.9, P = 0.3). Growth rates were not affected by the addition of GSH in
      fibroblasts from D and C. The treatment of fibroblasts from D and C with the
      inhibitor of the gamma-glutamylcysteine synthetase activity, L-buthionine-S,R
      sulfoximine, resulted in growth impairment, and the addition to the culture
      medium of another antioxidant, superoxide dismutase, corrected the growth
      abnormalities in fibroblasts from DN. The impaired growth of cultured fibroblasts
      from IDDM patients with nephropathy is prevented by GSH and superoxide dismutase
      and is independent of prevailing glucose concentrations. This suggests that
      oxidative stress is an important mechanism of intrinsic cell dysfunction in these
      patients.

PMID- 9621290
TI  - Leucine turnover in patients with nephrotic syndrome: evidence suggesting body
      protein conservation.
AB  - Whole-body leucine flux was measured in eight patients with nephrotic syndrome
      and in five healthy subjects by primed-constant infusion of L-[1-13C leucine].
      Plasma enrichment of 13C leucine and 13C alpha-keto-isocaproate (13C KIC) was
      measured by gas chromatography/mass spectrometry, and expired 13CO2 was measured
      by isotope ration mass spectrometry. Leucine kinetics, calculated from the
      primary pool enrichment [13C leucine], showed no difference between the nephrotic
      patients and the control subjects. Kinetics derived from the reciprocal pool [1
      13C KIC] enrichment, however, showed that leucine turnover rates were reduced in
      the nephrotic patients. The values (mumol/kg per h, means +/- SD) comparing the
      patients and the control subjects are as follows: rate of leucine release from
      protein degradation, 99 +/- 6 and 117 +/- 12 (P = 0.007); leucine oxidation rate,
      15 +/- 7 and 22 +/- 3 (P = 0.04); rate of leucine incorporation into body protein
      [S], 84 +/- 10 and 95 +/- 6 (P = 0.04); protein turnover rate, 3.99 +/- 0.49 and
      4.72 +/- 0.25 g/kg per d (P = 0.007). Nitrogen balance, measured only in the
      nephrotic patients, showed a mean positive balance of 0.5 g/d. In the nephrotic
      and control subjects, protein intake levels were 0.84 +/- 0.16 and 1.17 +/- 0.18
      g/kg per d (P = 0.002), respectively, and energy intake levels were 33.3 +/- 8.5
      and 33.9 +/- 2.4 kcal/kg per d, respectively. Linear correlations between leucine
      turnover rates and protein intake were highly significant. This study found that
      nephrotic patients given a modestly protein-restricted diet were able to maintain
      positive nitrogen balance. Moreover, leucine flux measurements showed
      downregulation of protein degradation and amino acid oxidation, reflecting
      appropriate adaptation to a lower protein intake.

PMID- 9621291
TI  - Inappropriate elevation of serum leptin levels in children with chronic renal
      failure. European Study Group for Nutritional Treatment of Chronic Renal Failure
      in Childhood.
AB  - Decreased spontaneous nutrient intake is a frequent clinical problem in patients
      with chronic renal failure (CRF). Leptin, the recently characterized gene product
      of the obese gene, is produced by adipocytes and is thought to act as an afferent
      satiety signal on the appetite and satiety centers of the brain. Serum leptin
      levels were investigated in 134 pediatric patients in different stages of CRF to
      evaluate a possible relationship between leptin, GFR, and spontaneous energy
      intake. Serum leptin levels, measured by a specific RIA, were elevated above the
      50th percentile of the normal range in 78% of CRF patients and above the 95th
      percentile in 45% of patients. Gel chromatography of CRF sera yielded only one
      single immunoreactive peak at 16 kD, indicating that the increase of
      immunoreactive leptin levels in CRF serum was not due to accumulation of leptin
      degradation products. Multiple stepwise regression analysis revealed the
      percentage of body fat as assessed from skinfold measurements (r = 0.79, P <
      0.0001) and GFR (r = -0.17, P < 0.005) as independent predictors of serum leptin
      levels, accounting for 66% of total statistical variability. There was an inverse
      linear correlation between standardized leptin levels (leptin z-score) and the
      spontaneous energy intake quantified from written dietary diaries (r = -0.36, P <
      0.001). These data suggest that the percentage of body fat remains the main
      determinant of serum leptin in CRF patients, but their levels increase with
      declining GFR, presumably by reduced renal clearance. Leptin levels in CRF serum
      that are inappropriately elevated in relation to the percentage of body fat might
      lead to a dysregulation of the normal peripheral-central leptin feedback loop,
      thereby contributing to decreased nutrient intake in uremia.

PMID- 9621292
TI  - Leptin, body composition, and indices of malnutrition in patients on dialysis.
AB  - A cross-sectional study was performed in a group of dialysis patients and control
      subjects to identify the determinants of serum levels of leptin, the protein
      product of the obese (ob) gene. Twenty-eight patients on dialysis (19 patients on
      hemodialysis [HD] and nine patients on peritoneal dialysis [PD]) and 41 healthy
      control subjects were studied. For each subject, blood was drawn for measurement
      of serum leptin levels and body composition was analyzed by dual-energy x-ray
      absorptiometry. Regression analyses were performed to determine the predictors of
      leptin levels, the independent contribution of HD and PD, and the relationship
      between leptin levels and markers of malnutrition and protein intake in the
      patients on dialysis. As expected, percentage of body fat was strongly correlated
      with leptin levels in the group as a whole and in each subgroup when analyzed
      separately. However, the slope of the relationship was significantly greater for
      dialysis patients than for control subjects (P < 0.05). Multivariate regression
      analysis showed that patients on HD and PD had higher leptin levels than control
      subjects even after adjustment for age, gender, and percentage of body fat.
      Univariate analyses were performed to assess the relationship between leptin
      levels and markers of nutritional status such as albumin, blood urea nitrogen,
      protein catabolic rate (PCR), transferrin, cholesterol, and lean body mass per
      height. There was a significant negative correlation between leptin levels and
      serum albumin (r = -0.598, P < 0.001) and between leptin and PCR (r = -0.433, P <
      0.05) in the patients on dialysis. It is concluded that leptin levels adjusted
      for percentage of body fat are increased in dialysis patients compared with
      control subjects, particularly in those on PD. In addition, increased leptin
      levels are associated with low serum albumin levels and PCR in dialysis patients.

PMID- 9621293
TI  - Staphylococcus aureus prophylaxis in hemodialysis patients using central venous
      catheter: effect of mupirocin ointment.
AB  - Central venous catheterization is a common technique to establish rapid and
      temporary access for hemodialysis. However, it is a known risk factor for
      Staphylococcus aureus infection and bacteremia. Mupirocin is a topical antibiotic
      with high in vitro anti-staphylococcal activity. A randomized prospective trial
      was conducted to assess the effectiveness of mupirocin ointment in the prevention
      of Staphylococcus aureus skin and catheter colonization, and episodes of
      bacteremia in 136 end-stage renal disease patients. Of these, 67 received skin
      disinfection at the venous catheter insertion site with povidone iodine (control
      group), and 69 received the same treatment followed by application of 2%
      mupirocin ointment at the cannula site after catheter placement and at the end of
      each dialysis session. Patients were followed until catheter removal and were
      monitored for the development of Staphylococcus aureus skin/catheter colonization
      and episodes of bacteremia. Median duration of catheter use was greater in the
      mupirocin than in the control group (37 versus 20 d, P < 0.01). Patients in the
      mupirocin group had a significantly lower rate of Staphylococcus aureus isolation
      from the pericatheter skin (1.76 per 1000 versus 14.27 per 1000 patient-days, P <
      0.001) and from the catheter surface (3.17 per 1000 versus 14.27 per 1000 patient
      days, P < 0.001). The proportion of patients with Staphylococcus aureus skin
      infection at the insertion site was lower in the mupirocin group (4.3% versus
      23.9%, P = 0.001). Staphylococcus aureus-associated bacteremia was observed in 17
      patients (two in the mupirocin group [0.71 episodes per 1000 patient-days] and 15
      in the control group [8.92 per 1000 patient-days], P < 0.001). The hazard ratio
      of developing Staphylococcus aureus bacteremia was 7.2 (95% confidence interval,
      1.6 to 31.6) times greater in patients not receiving mupirocin. Mupirocin applied
      to the insertion site significantly reduces the risk of Staphylococcus aureus
      skin and catheter colonization, exit-site infection, and Staphylococcus aureus
      bacteremia in hemodialysis patients.

PMID- 9621294
TI  - Elevation of whole-blood glutathione in peritoneal dialysis patients by L-2
      oxothiazolidine-4-carboxylate, a cysteine prodrug (Procysteine).
AB  - Glutathione is a major cellular antioxidant that protects protein thiols and
      inhibits cellular damage due to oxygen free radicals. It has been reported
      previously that patients undergoing dialysis have low levels of blood
      glutathione, which may lead to increased susceptibility to oxidant stress. L-2
      oxothiazolidine-4-carboxylic acid (OTZ) is a cysteine prodrug that raises
      cellular glutathione levels by increasing delivery of cysteine, the rate-limiting
      substrate for glutathione synthesis. This study investigates the effect of OTZ on
      blood glutathione in a blinded, placebo-controlled study of patients with chronic
      renal failure treated by peritoneal dialysis. Twenty patients were randomly
      selected to receive OTZ (0.5 g three times a day orally with meals) or placebo
      for 14 d. Patients visited the clinic for predose blood collection and safety
      evaluation at baseline (days 3, 7, and 14 and again at 14 d from the last dose
      [follow-up]). Glutathione concentrations were determined in whole blood by HPLC.
      OTZ resulted in a significant rise in whole-blood glutathione at days 7 (594 +/-
      129 mumol/L) and 14 (620 +/- 108 mumol/L) compared with baseline (544 +/- 139
      mumol/L) (P < 0.01 and P < 0.05, respectively). Glutathione was also
      significantly increased at days 7 and 14 when normalized by hematocrit (Hct) or
      hemoglobin to correct for anemic status (e.g., 20.7 +/- 5.7 mumol/L per % Hct
      [day 7] and 20.9 +/- 4.0 mumol/L per % Hct [day 14] versus 18.0 +/- 4.2 mumol/L
      per % Hct [baseline]; P < 0.05). Glutathione levels did not change in the placebo
      group at any patient visit, and levels in the OTZ-treated group returned to
      baseline at follow-up. There were no serious adverse events attributable to OTZ,
      and the drug appeared to be well tolerated by patients with renal failure treated
      by continuous ambulatory peritoneal dialysis. Our results show that OTZ increases
      blood glutathione levels, which may improve antioxidant status in dialysis
      patients.

PMID- 9621295
TI  - Living unrelated (commercial) renal transplantation in children.
AB  - Long waiting times for cadaveric renal transplantation has led the frustrated
      parents of Arab children with end-stage renal disease treated in our center to
      seek commercial renal transplantation (CRT) outside Israel. During the past 3 yr,
      18 children, aged 13 +/- 1 yr, underwent CRT in one center in Iraq. Post-CRT
      follow-up was 20.2 +/- 2.5 mo. Immediate complications (abroad) included: death
      on the day of surgery (n = 1) and vascular thrombotic events requiring removal of
      a previously functioning graft (n = 2). There was a high incidence of urologic
      problems, mainly as a result of inadequate uretero-vesical anastomosis.
      Calculated creatinine clearance at 6, 12, 18, 24, and 30 mo was 84.7 +/- 6.4,
      91.0 +/- 6.8, 90.8 +/- 6.2, 82.5 +/- 9.5, and 77.7 +/- 8.2 ml/min per 1.73 m2
      respectively, representing excellent graft function in 13 patients and slightly
      compromised function in two children. One- and two-year patient survival was
      94.4%, with a graft survival of 83.3%. CRT in these Arab children had a favorable
      outcome despite severe early postoperative complications. Graft function at
      follow-up was comparable to cadaveric renal transplantation in Israel. This may
      reflect a propensity for healthy young adult donors. Despite these results, the
      authors oppose and discourage the practice of CRT on legal and ethical grounds.
      Not to provide follow-up care in this specific group of patients would not have
      been in their best interest.

PMID- 9621296
TI  - Losartan, an angiotensin II type 1 receptor antagonist, lowers hematocrit in
      posttransplant erythrocytosis.
AB  - The mechanism by which angiotensin-converting enzyme inhibitors reduce red cell
      mass in renal transplant recipients with erythrocytosis is unclear. To examine
      the role of angiotensin II in this disorder, losartan (a competitive antagonist
      of the angiotensin II type 1 [AT1] receptor) was administered to 23 patients with
      erythrocytosis. Fourteen patients took 25 mg/d for 8 wk; nine others were treated
      with 50 mg/d for 8 wk. Hematocrit decreased from 0.527 +/- 0.027 to 0.487 +/-
      0.045 after 8 wk (P < 0.01)--by at least 0.04 in 19 patients. Decrement in
      hematocrit in the initial 8 wk of therapy was significantly greater in patients
      administered 50 mg/d than in patients on 25 mg/d. Twelve of 14 patients initially
      treated with 25 mg/d showed a small change in hematocrit; the dose was increased
      to 50 mg/d for 8 more wk. Hematocrit decreased from 0.528 +/- 0.030 before
      losartan treatment to 0.483 +/- 0.055 after 16 wk (P < 0.01). After therapy,
      serum erythropoietin significantly decreased in eight patients with elevated
      baseline levels, but not in 15 patients with normal baseline levels; however,
      hematocrit significantly decreased in both groups. Losartan was withdrawn in 16
      patients; hematocrit increased from 0.440 +/- 0.057 to 0.495 +/- 0.049 after 8.9
      +/- 7.5 wk (P < 0.001), without change in serum erythropoietin. Thus, specific
      blockade of AT1 receptors inhibited erythropoiesis, suggesting a pathogenic role
      for angiotensin II in posttransplant erythrocytosis.

PMID- 9621297
TI  - Fibrosing cholestatic hepatitis in hepatitis C virus-infected renal transplant
      recipients.
AB  - Severe hepatitis C virus (HCV)-related fibrosing cholestatic hepatitis leading to
      early liver failure has been reported only exceptionally. Of 259 HCV-infected
      renal transplant (RT) patients in one hospital unit, four (1.5%) are described,
      representing the first series of this particular post-RT disease. Patient mean
      age was 55.7 yr. Three were men. All had pretransplant, hepatitis B surface
      antigen-negative and were anti-HCV antibodies positive. Three of them showed
      pretransplant mild liver enzyme abnormalities, and all received kidneys from HCV
      negative donors. All were on steroids, cyclosporine, and azathioprine (AZA). The
      clinical pattern appeared early after RT (mean, 11.5 mo). In three patients,
      hyperbilirubinemia (6.5 to 20 mg/dl) and high alkaline phosphatase levels (428 to
      859 IU/L) were observed. Also, in all subjects, high gamma glutamyl
      transpeptidase levels (639 to 4270 IU/L), mild aspartate aminotransferase and
      alanine aminotransferase abnormalities, and serum HCV RNA were observed. Liver
      biopsy revealed diffuse fibrosis, leukocyte infiltrates, and different degrees of
      cholestasis, with typical signs of HCV hepatitis in only one patient. Two
      patients developed subfulminant liver failure and died 2 and 3 mo after biopsy,
      respectively. One patient also suffered hepatic failure, receiving a liver
      transplant. The fourth is alive on dialysis awaiting a combined kidney and liver
      transplant. It is concluded that fibrosing cholestatic hepatitis is a new, early,
      and severe complication after RT in HCV(+) patients, which appears in patients
      with ongoing HCV infection under AZA therapy, despite a nonaggressive
      immunosuppressive protocol. Both HCV and AZA could play a concurrent role in the
      pathogenesis of this severe complication after RT.

PMID- 9621298
TI  - Advances in the cell biology and genetics of human kidney malformations.

PMID- 9621299
TI  - The pathogenesis and treatment of hemolytic uremic syndrome.

PMID- 9621300
TI  - The mechanism of bicarbonate reabsorption in the proximal and distal tubules of
      the kidney. 1965.
AB  - The mechanism of HCO3- reabsorption in proximal and distal tubules was examined
      in rats undergoing NaHCO3 diuresis. The steady-state intratubular pH was measured
      with pH-sensitive glass microelectrodes and compared with the equilibrium pH
      calculated from the HCO3- concentration of the tubular fluid (measured with
      quinhydrone electrodes) and plasma Pco2. In the proximal tubule the intratubular
      pH and the equilibrium pH were identical, indicating no accumulation of excess
      H2CO3. After inhibition of carbonic anhydrase, however, intratubular pH was
      significantly lower (0.85 pH U) than the equilibrium pH. It was concluded that
      HCO3- reabsorption in the proximal tubule was mediated by H+ secretion, but that
      carbonic anhydrase located in the luminal membrane of the cell prevented H2CO3
      from accumulating in the tubular fluid. In the distal tubule the intratubular pH
      was 0.85 U lower than the equilibrium pH. This difference could be obliterated by
      an intravenous injection of carbonic anhydrase. It was concluded that HCO3-
      reabsorption in this segment was also accomplished by H+ secretion. The
      accumulation of excess H2CO3 in the tubular fluid indicated that, in contrast to
      the proximal tubule, carbonic anhydrase was not located in the luminal membrane
      of distal tubular cells.

PMID- 9621301
TI  - p34cdc2 expression and meiotic competence in growing goat oocytes.
AB  - The expression of the catalytic subunit of the maturation promoting factor (MPF),
      p34cdc2, was analyzed during meiosis and final growth of goat oocytes. Western
      blot analysis revealed the presence of p34cdc2 in fully grown oocytes (follicles
      > 3 mm in diameter) prior to and during meiotic maturation. p34cdc2 was present
      in partially competent oocytes at the germinal vesicle stage (follicles 0.5 to
      0.8 mm and 1 to 1.8 mm in diameter). In contrast, p34cdc2 was not expressed in
      meiotically incompetent oocytes from small antral follicles (follicles < 0.5 mm
      in diameter). The amount of p34cdc2 increased with oocyte growth and acquistion
      of meiotic competence. Moreover, p34cdc2 accumulated in partially competent and
      incompetent oocytes within 27 hr of culture, but the level of p34cdc2 in
      incompetent oocytes remained very low and was not sufficient to allow spontaneous
      resumption of meiosis. The expression of the cdc2 gene was analyzed by polymerase
      chain-reaction (PCR) on reverse transcribed mRNA. The presence of the cdc2
      transcript was evidenced in both competent and incompetent oocytes at the
      germinal vesicle stage. These data indicate that a deficiency in the expression
      of p34cdc2 that could be regulated at the translational level, may be a limiting
      factor for meiotic competence acquistion in goat oocytes. We further investigated
      the mechanisms of MPF activation in competent and incompetent oocytes by using
      okadaic acid, a protein phosphatase inhibitor. Okadaic acid induced the premature
      resumption of meiosis associated with MPF activation in competent oocytes. In
      partially competent oocytes, okadaic acid induced premature meiosis reinitiation
      and MPF activation, but only after pre-culture for 10 hr. Acquisition of
      sensitivity to okadaic acid treatment was dependent on protein synthesis since it
      failed to occur when cycloheximide was added during the pre-culture period.
      Incompetent oocytes responded to okadaic acid treatment only after 27 hr of
      culture, when they had accumulated small amounts of p34cdc2. These data suggest
      that okadaic acid may bypass the subthreshold level of p34cdc2, provided the
      oocytes have synthesized some additional factors that remain to be identified.

PMID- 9621302
TI  - Immunofluorescent localization of actin in relation to transcription sites in
      mouse pronuclei.
AB  - Previous biochemical and morphological studies have shown the presence of actin
      in the nucleus of different cell types where its role remains unclear. In this
      work, through fluorescence microscopy we studied the localization of actin in the
      nuclei of early mouse embryos with particular attention to its possible
      involvement in the onset of transcription occurring at the late one-cell stage.
      Fluorescent labelling of embryo sections showed that nuclear actin in abundant,
      in a non-filamentous state, in the whole nucleoplasm excluding the nucleolar
      precursor bodies. Immunofluorescence on permeabilized embryos revealed that
      insoluble nuclear actin accumulates in a few large aggregates in
      transcriptionally inert early one-cell embryos and progressively redistributes
      into many small aggregates in transcriptionally active late one-cell embryos.
      Interestingly, these actin aggregates clearly colocalize with transcription
      sites. Treatment of late one-cell embryos with cytochalasin D induces the
      formation of actin bundles network in the nucleoplasm but has no apparent effect
      on the transcriptional activity. In addition, the inhibition of transcription by
      alpha-amanitin does not modify the nuclear actin distribution. Hence, there does
      not appear to be a direct causal relationship between transcriptional activity
      and nuclear actin organization at the one-cell stage although nuclear actin
      aggregates appear associated with transcription sites.

PMID- 9621303
TI  - Comparative sequence analysis of the mouse and human transferrin promoters:
      hormonal regulation of the transferrin promoter in Sertoli cells.
AB  - Cell-specific expression of the iron-binding protein transferrin is in part
      mediated through the regulation of its promoter. Although all cells require iron
      from serum transferrin produced by hepatocytes, cells that create a blood barrier
      such as Sertoli cells in the testis and choroid plexus epithelium in the brain
      also express the transferrin gene to provide iron to cells sequestered within the
      serum-free environment. The current study provides a complete sequence of the 3
      kb mouse transferrin promoter and makes a comparison with the sequence available
      for the human transferrin promoter. Conserved regulatory elements between these
      two species are identified and speculated to be potentially important response
      elements for the regulation of the transferrin gene. The proximal 90 bp of the
      mouse and human transferrin promoter was found to be 80% homologous. The
      previously identified protected regions in the proximal human promoter also were
      conserved in the mouse transferrin promoter. Our sequence analysis data revealed
      that an E-box response element is also conserved between mouse and human
      promoters. Deletion mutants of the mouse transferrin promoter were generated in
      CAT reporter constructs to study the regulation of the transferrin promoter in
      Sertoli cells. As in the case of the human transferrin promoter, the mouse 581-bp
      proximal transferrin promoter was sufficient to obtain basal expression. A
      putative cyclic AMP response element (CRE) in the minimal promoter may be needed
      for follicle-stimulating hormone (FSH) actions mediated via cyclic AMP.
      Interestingly, other regulatory agents such as the testicular paracrine factor
      PModS used elements in the upstream region. A repressor was identified 2.5 kb
      upstream from the start site of translation. Combined observations suggest for
      the first time that a minimal promoter is sufficient for basal transcription, but
      the upstream regions of the promoter are needed for the hormonal regulation of
      the transferrin gene in Sertoli cells. Conserved response elements between the
      mouse and human sequences identify potentially important regulatory elements of
      the promoter and are discussed.

PMID- 9621304
TI  - Expression of the human antigen SPAG2 in the testis and localization to the outer
      dense fibers in spermatozoa.
AB  - ABSTRACT Antisperm antibodies (ASAs) have been implicated in some instances of
      infertility. To characterize sperm antigens relevant to immunologic and
      immunocontraceptive development, SPAG2 (sperm-associated antigen 2) was
      identified by screening a human testis cDNA library with human sera positive for
      ASAs. Subsequently, two isoforms, SPAG2-1 and SPAG2-2, were identified in testis
      and placenta libraries, respectively. In the current study, Southern analysis of
      human genomic DNA with a probe common to the two SPAG2 isoforms indicated a
      single SPAG2 gene; therefore, alternative splicing is a likely mechanism for
      production of variant mRNAs. In situ hybridization of human testis sections
      demonstrated the expression of SPAG2 in primary spermatocytes, with decreased or
      arrested expression in postmeiotic cells. Immunofluorescence of Triton X-100
      extracted spermatozoa with an anti-SPAG2 peptide antiserum indicate that SPAG2 is
      an intracellular component of the sperm flagellum. Electron microscopy refined
      this localization to the outer dense fibers (ODFs), structural filaments
      associated with the mammalian sperm axoneme. The ODFs have been reported to be
      composed of keratin-like intermediate filament proteins. However, SPAG2 does not
      exhibit the molecular characteristics of such proteins, nor does SPAG2
      demonstrate sequence homology with previously characterized ODF proteins.
      Therefore, SPAG2 represents a novel protein of human sperm ODFs. Characterization
      of SPAG2 will further our understanding of ODF function in normal sperm motility
      and of flagellar abnormalities that lead to male infertility.

PMID- 9621305
TI  - Effects of recombinant activin A on in vitro culture of mouse preantral
      follicles.
AB  - Activins are part of the intragonadal factors that can modulate the actions of
      gonadotropins and regulate cellular functions during preantral or early antral
      stages of folliculogenesis in vivo. In a mouse early preantral follicle culture
      system, activin A production was measured and recombinant bovine activin A (r-ACT
      A) was added (10 or 50 ng/ml) to recombinant follicle-stimulating hormone (r-FSH)
      supplemented (10 or 100 mIU/ml) medium for a 12-day culture period. Specificity
      of activin A action was ascertained by addition of recombinant human follistatin
      (r-FA; 20 or 100 ng/ml). Immunoreactive activin A concentrations in mouse
      follicle-conditioned medium increased by a factor of 20-50, reaching
      concentrations from 2 to 5 ng/ml at end of culture. In the initial days of
      culture, additions of r-ACT A to r-FSH-supplemented medium provoked a dramatic
      volumetric increase and earlier attachment of the follicle. A dose of 100 ng/ml r
      FS was able to block the actions of 10 ng/ml but not those caused by 50 ng/ml r
      ACT A. In follicle cultures supplemented with 10 mIU/ml r-FSH, additions of r-ACT
      induced a dose-dependent inhibin (INH) and estradiol (E2) increase. Basal and
      human chorionic gonadotropin (HCG)-induced progesterone (P) production were not
      influenced by r-ACT A or r-FS additions. Addition of r-ACT A decreased (P =
      0.017) the intact follicle survival rate and had no influence on final oocyte
      diameter. In cultures supplemented by 10 mIU/ml r-FSH, additions of r-ACT A did
      not influence progression and resumption of meiosis I. Use of a higher r-FSH
      supplementation dose (100 mIU/ml) tended to affect meiosis I adversely (P =
      0.052), and r-ACT A addition amplified this effect significantly (P = 0.007).
      These in vitro experiments demonstrate pronounced effects from r-ACT on r-FSH
      mediated follicle survival, growth, and estrogen biosynthesis.

PMID- 9621306
TI  - Analysis of aneuploidy rate in antral and ovulated mouse oocytes during female
      aging.
AB  - Two forms of oocytes termed SN (surrounded nucleolus) and NSN (nonsurrounded
      nucleolus) differing for the spatial distribution of nuclear and nucleolar
      associated chromatin have been described within the antral compartment of the
      ovary of a number of mammals. The biological significance of these two kind of
      oocytes is as yet not completely clear. In previous studies we have shown that
      prior to ovulation, mouse SN oocytes isolated from the antral compartment,
      matured and fertilized in vitro have a far better meiotic and developmental
      competence than NSN oocytes. Immediately after ovulation SN and NSN oocytes
      remaining in the antral compartment do not develop beyond the 2-cell stage. To
      further examine the correlation between chromatin distribution and meiotic
      competence of mouse antral oocytes, in the present study we have analyzed
      chromosome segregation at the first meiotic division in antral (SN and NSN) and
      in ovulated oocytes. SN and NSN oocytes were isolated before (48 h post PMSG
      injection) or after (15 h post-hCG injection) ovulation from ovaries of females
      of increasing age, they were cultured in vitro to metaphase II, and their
      aneuploidy rate was examined. Comparison of data obtained before and after
      ovulation highlights two main points: 1. Following ovulation a statistically
      significant increase of aneuploidy is observed in antral oocytes in most age
      groups and it is attributable to SN oocytes. 2. The aneuploidy rate of ovulated
      oocytes does not increase during female aging. We have found a correlation
      between chromatin distribution, hormonal status, and the incidence of aneuploidy
      during the oocyte first meiotic division.

PMID- 9621307
TI  - Identification of a rat testis-specific gene encoding a potential rat outer dense
      fibre protein.
AB  - Screening of a rat testis expression library with an antiserum specific for an
      outer dense fibre (ODF) has led to the identification of a gene encoding for a
      putative protein previously unknown as a component of the sperm tail. This gene
      has been designated tpx-1 by virtue of its homology with the mouse and human gene
      of the same name (79 and 73%, respectively). The tpx-1-like gene encoded a 1.6-kb
      mRNA and a 243-amino-acid protein that had significant homology with members of
      the cysteine-rich secretory protein (CRISP) family and partial homology with
      several venom/allergen proteins from both plants and insects. During rat
      spermatogenesis, the tpx-1-like transcript was first detected by in situ
      hybridization in low levels in late pachytene spermatocytes. Low but detectable
      levels of expression continued up to step 5 round spermatids, after which
      expression levels increased dramatically to a maximum in step 11-12 spermatids.
      Progressively decreasing levels of expression were detected in up to step 17
      elongating spermatids. Testicular somatic cells did not contain detectable tpx-1
      like transcript. This pattern of expression is consistent with published data on
      the development of the ODF in spermatogenesis and, when taken together with a
      comparison of the predicted amino acid sequence of tpx-1 with the amino acid
      analysis of a 29-kDa rat ODF protein, suggests that the tpx-1-like gene may
      encode for this protein.

PMID- 9621308
TI  - Comparative motility of X and Y chromosome-bearing bovine sperm separated on the
      basis of DNA content by flow sorting.
AB  - A combination of flow cytometric sperm sorting of X and Y chromosome-bearing
      sperm (X and Y sperm) and computer-assisted sperm analysis (CASA) for measuring
      sperm motility allows assessment of motion parameters in the two populations.
      Bull sperm were separated into X and Y populations by flow cytometry following
      staining with the DNA-binding dye Hoechst 33,342. The motion parameters differed
      depending on sperm concentration. Decreasing sperm concentration resulted in
      higher velocities and straighter trajectories. The concentrations of control
      (stained-unsorted and unstained-unsorted) and flow-sorted sperm were therefore
      adjusted to similar numbers (5 x 10(6) sperm per milliliter). Samples of sorted X
      and Y sperm and control sperm were transferred to prewarmed slides on a heated
      stage (37 degrees C) and their motion video recorded for 2 min using a
      magnification of x 100 and a high-resolution camera. The sperm analysis was
      carried out on a Hobson Sperm Tracker (HST) using HST 7 software. The following
      motion parameters were measured: curvilinear, straight-line, and average path
      velocity; mean angular displacement (MAD); beat cross-frequency; amplitude of
      lateral head displacement; linearity (LIN); and straightness of path (STR). Sperm
      movement was unaffected by staining with Hoechst 33,342, excitation by
      ultraviolet (UV) light, or the physical process of cell sorting. Significant
      differences were seen between X and Y sperm for MAD, LIN, and STR. No difference
      was observed for the other parameters. The results indicate that in a simple
      salts solution, Y bull sperm do not swim faster than X sperm but may be
      distinguished from X sperm on the basis of LIN and STR.

PMID- 9621309
TI  - Fertilization characteristics and in vitro embryo production with bovine sperm
      containing multiple nuclear vacuoles.
AB  - An in vitro fertilization and culture system was used to determine the effect of
      multiple nuclear vacuoles in bovine spermatozoa on fertilization and early
      embryonic development. After swim-up, semen parameters were similar between 2
      bulls except that 60% of spermatozoa from bull A contained multiple nuclear
      vacuoles, whereas no spermatozoa from bull B (control) contained vacuoles. In
      Experiment 1, in vitro-matured (IVM) oocytes were inseminated with frozen-thawed
      semen from the 2 bulls to determine the ability of vacuolated sperm to bind with
      the zona pellucida. The mean number of spermatozoa bound to the zona pellucida
      was less (P < 0.05) for bull A (85.7 +/- 5.7; n = 112) than for bull B (108.9 +/-
      5.4; n = 130). In Experiment 2, the percentages of zonae penetrated by
      spermatozoa from bull A (151 of 201; 75%) and bull B (116 of 150; 77%) were not
      different. However, the percentages of vacuolated spermatozoa from bull A bound
      to (43%) and penetrating the zona pellucida (34%) were lower than those in the
      inseminate (60%). In Experiment 3, fertilization rates, as evidenced by the
      presence of two pronuclei, were not different for bull A (101 of 136; 74%) and
      bull B (89 of 115; 77%). In Experiment 4, there was no significant difference in
      percentage cleavage (72.1% versus 76%) and morulae (29.2% versus 34.8%) or
      blastocyst production (7.2% versus 8.4%) for bulls A and B, respectively. Data
      suggest that spermatozoa with multiple nuclear vacuoles are defective in zona
      binding. However, vacuolated spermatozoa gaining access to the ooplasm apparently
      participate in fertilization and early embryonic development.

PMID- 9621310
TI  - Embryo development, oocyte morphology, and kinetics of meiotic maturation in
      bovine oocytes exposed to 6-dimethylaminopurine prior to in vitro maturation.
AB  - The developmental competence of bovine follicular oocytes that had been
      meiotically arrested with the phosphokinase inhibitor 6-dimethylaminopurine (6
      DMAP) was studied. After 24 h in vitro culture with 2 mM 6-DMAP, 85 +/- 12% of
      the oocytes were at the germinal vesicle stage compared to 97 +/- 3% at the start
      of culture (P > 0.05). After release of the 6-DMAP inhibition, followed by 24 h
      IVM, 82 +/- 18% were at MII stage, compared with 93 +/- 7% in the control group
      (P > 0.05). The 6-DMAP oocytes displayed a much higher frequency of abnormal MII
      configurations than the control oocytes (67% vs 23%; P < 0.0001). In addition
      spontaneous oocyte activation was more frequent than among control oocytes (5% vs
      0.3%; P 0.0006). After IVF of 6-DMAP oocytes, normal fertilization was lower (76
      +/- 8% vs 89 +/- 7%; P < 0.01), oocyte activation higher (11 +/- 5% vs 2 +/- 2%;
      P < 0.01), and polyspermy slightly but not significantly higher (8 +/- 7% vs 4 +/
      4%; P > 0.05), compared with the control group. Cleavage was lower (61 +/- 13%
      vs 81 +/- 6%; P < 0.001), as well as day 8 blastocyst formation (17 +/- 7% vs 36
      +/- 8%; P < 0.001). The MII kinetics was different for 6-DMAP and control
      oocytes. Maximum MII levels were reached at 22 h IVM in both groups, but 50% MII
      was reached at 17 h in 6-DMAP oocytes, compared to 20 h in control oocytes.
      Ultrastructure of MII oocytes was similar in the two groups, but in 6-DMAP
      oocytes the ooplasmic vesicle pattern at GV was at a more advanced stage than in
      control oocytes. In conclusion, 6-DMAP exposure of GV oocytes prior to IVM induce
      asynchronous cytoplasmic maturation, leading to aberrant MII kinetics. Thus, at
      the time of insemination a smaller cohort of oocytes will be at the optimal stage
      for normal fertilization and subsequent blastocyst development.

PMID- 9621311
TI  - Protein and DNA contents in sperm from an infertile human male possessing
      protamine defects that vary over time.
AB  - Sperm from 2 semen samples collected 6 months apart from an infertile male and 3
      semen samples collected over an 18-month period from a fertile human male
      volunteer have been analyzed for their protamine and DNA content. Hup1M and Hup2b
      antibodies were used to detect the presence of protamines and protamine
      precursors in western blots of nuclear proteins isolated from pools of sperm.
      Phosphorus and sulfur contents, which can be used to estimate the nuclear DNA and
      protamine contents of sperm from fertile males, were measured within individual
      sperm heads from each semen sample by particle induced x-ray emission (PIXE). The
      single-cell data reveal no significant differences in the phosphorus and sulfur
      contents of sperm heads in the three semen samples obtained from the fertile
      male. For the initial semen sample produced by the infertile male, Western blot
      data show a normal complement of protamine 1, small amounts of mature protamine
      2, and reveal large amounts of anti-protamine 2 reactive proteins with
      electrophoretic mobilities similar to protamine 2 precursors. Data from PIXE show
      elevated levels of sulfur within sperm heads compared with sperm from the fertile
      male. Western blot data exhibit no evidence of protamines or protamine 2
      precursors in the second semen sample produced by the infertile male. Data from
      PIXE suggest that these sperm are highly deficient in sulfur and protamines.
      These results show that the degree of maturation of sperm cells present in the
      semen of some infertile males can vary with time.

PMID- 9621312
TI  - Ion-channels reconstituted into lipid bilayer from human sperm plasma membrane.
AB  - Ion environment and ionic fluxes through membrane are thought to be important in
      the spermatozoa's maturation, capacitation, and the initiating process of gamete
      interaction. In this work, the membrane proteins isolated from human sperm plasma
      membrane were reconstituted into planar lipid bilayers via fusion, and the ion
      channels activities were observed under voltage clamp mode. In cis 200//trans 100
      mM KCl solution, a TEA-sensitive cation-selective channel with a unit conductance
      of 40 pS was recorded. In a gradient of 200//100 mM NaCl solutions, a Na(+)
      selective channel with a unit conductance of 26 pS was recorded. In both cases,
      reversal potential was about-18 mV, which is close to the predicated value of a
      perfect Nernst K+ or Na+ electrode. In 50//10 mM CaCl2 solution, a cation channel
      activity with a unit conductance of 40 pS and reversal potential of about -20 mV
      was usually observed. In 200//100 mM NMDG(N-methyl-D-glucamine)-Cl solution,
      where the cation ions were substituted with NMDG, a 30-pS anion-selective channel
      activity was also detected. The variety in the types of ion channels observed in
      human spermatozoa plasma membrane suggests that ion channels may play a range of
      different roles in sperm physiology and gamete interaction.

PMID- 9621313
TI  - Calcium elevation in sheep cumulus-oocyte complexes after luteinising hormone
      stimulation.
AB  - We investigated Ca2+ levels in intact cumulus-oocyte complexes (COCs) on exposure
      to peak levels of luteinising hormone (LH). Specific preparations were used where
      cumulus corona cells were loaded with a membrane-permeant Ca(2+)-sensitive dye
      (FLUO-3AM), whereas the oocyte was injected directly with the nonpermeant form of
      the dye (FLUO-3). After exposure to LH, cumulus and corona radiata cells showed
      distinct rises in intracellular Ca2+ in 50-200 sec. The pattern of Ca2+ response
      varied in the different cells both for the duration of the transients and for
      their persistence. Interestingly, Ca2+ elevations were recorded in all the layers
      of the cumulus mass, including the innermost layer of corona cells, demonstrating
      the wide diffusion of LH receptors. Following the Ca2+ raise in somatic cells, an
      intracellular Ca2+ elevation also was recorded within the oocyte with a delay of
      100-300 sec. The elevation started at the cortex of the oocyte and then spread
      all over the ooplasm. The addition of verapamil or manganese chloride did not
      prevent LH-induced Ca2+ elevation in the COC, whereas mechanical uncoupling of
      cumulus cells from the oocyte prevented any Ca2+ response within the oocyte. The
      results indicate that cumulus corona cells are capable of transducing LH message
      by rising intracellular Ca2+ and show that this signal is rapidly transferred
      into the oocyte through gap junctions. This may result from the direct diffusion
      of Ca2+ or its putative releaser IP3 from cumulus cells to the oocyte.

PMID- 9621314
TI  - Developmental origin of avian primordial germ cells and its unique
      differentiation in the gonads of mixed-sex chimeras.

PMID- 9621315
TI  - [Modelling of the 3-dimensional structure of the epithelia, constructed of bi-,
      tri and tetracellular modules].
AB  - A new approach for studying 3-dimensional histoarchitectonics of cellular layers
      is suggested. It is based on (1) development of theoretical concepts on module
      structure of tissues; (2) working out topological and geometrical models of
      tissue structure and; (3) their experimental testing using this approach. Spatial
      organization of certain stratified and pseudostratified epithelia was analysed
      and it was shown that their topology may be principally calculated. Such
      previously unknown characteristics of epithelia as translation symmetry and
      structure stoichiometry were described. This approach was shown to add to concept
      system of histology, reveal regularities of tissue spatial organisation and
      prognostic factors for their developmental changes. Cellular layers were shown to
      consist of a relatively small number of standard fragments (slices)--alone and
      arranged in different combinations thus providing a certain quantity of types of
      spatial organisations that is amenable to calculation.

PMID- 9621316
TI  - [Endocrine apparatus of the epithelium of the appendicular mucosa (the appendix--
      an endocrine gland, functioning in the embryonal period?].
AB  - Based on the concept on gastroenteropancreatic system, endocrinocytes of which
      are diffusely scattered throughout the digestive tract epithelium and are found
      in pancreatic islets, an analysis of endocrine apparatus of epithelium in human
      appendicular mucosa was performed at different stages of ontogenesis. The
      response of appendicular endocrinocytes to clinical pathology of both this organ
      and the entire organism was studied. On the base of the analysis of the appendix
      function from morphological view, the authors proposed a hypothesis postulating
      it to be an organ equal to an actively functioning endocrine gland and its unique
      role on early stages of embryogenesis.

PMID- 9621317
TI  - [Change in the content of chemical elements in epitheliocytes of the prickle cell
      layer of granulating skin wounds exposed to ultraviolet rays and ultraviolet
      laser therapy].
AB  - Spinous layer of human epidermis was studied in control group (2 human subjects)
      and in 16 patients with thermic lesions prior to and following ultraviolet laser
      therapy (UVLT) of ultraviolet irradiation (UVI). Skin biopsy was performed in
      each patient on undamaged regions (individual control). Chemical elements (Ca, K,
      Cl, Mg, Na and Al) content prior to and following treatment was compared.
      Patients with equal stage (IIIB) and localisation of lesion were selected.
      Bioptates were obtained for diagnostic purposes. UVLT was established to prompt
      normalization of the content of chemical elements named in epitheliocytes of
      human epidermis in IIIB lesions whereas UVI does not cause this effect at the
      same conditions. It is proposed that this difference is dependent on the origin
      of appropriate irradiations.

PMID- 9621318
TI  - [Structure of long-term transplants of embryonal anlages of the rat central
      nervous system].
AB  - Morphological investigation of transplants of the rat 14-15 d embryonal
      neocortical and spinal anlages after long term transplantation into the adult
      animal sciatic nerve was conducted. Transplants were shown to retain viability on
      19th month postoperatively, with the part of neurons demonstrating dystrophic
      changes and death. Neocortical neurons were shown to preserve higher viability in
      sciatic transplants. Increase in number of neurons showing irreversible changes
      correlates well with the development of degenerative changes in blood vessels,
      their calcification and formation of psammoma-like bodies.

PMID- 9621319
TI  - [Structural organization and Lugaro neuron connections in the cat cerebellar
      cortex].
AB  - Two types of intermedial Lugaro cells are distinguished in the cat cerebellum:
      fusiform (horizontal, vertical and obliquely oriented at angles 60-70 to
      longitudinal axis of folia cerebelli at different levels of granular layer) and
      those with triangular somata, sparsely branching dendrites and small number of
      spines. Both fusiform and triangular neuron axons do not stretch out beyond the
      borders of cerebellar cortex and may be thought of as recurrent interneurons as
      they contain GABA and glycine. Lugaro cells form numerous contacts almost with
      all cortical nervous elements: piriform (Purkinje) and Golgi cells, granular and
      basket neurons, parallel and mossy fibres and even unipolar, (brush) cells. At
      light microscopic level they are represented as axosomatic and axodendritic
      contacts. Lugaro cells are the only cerebellar cortical interneurons with
      dendritic arborizarion oriented in horizontal plane in contrast to vertical
      orientation of the other interneurons of cerebellar cortex.

PMID- 9621320
TI  - [Structural-quantitative characterization of nuclear and screen-like formations
      in the anterior section of the amygdaloid body of the brain].
AB  - Cytoarchitectonics and planimetry of structures of amygdaloid body anterior
      region were investigated in view of A.A. Zavarzin concepts on nuclear and screen
      type centres of nervous system. Amygdaloid body was shown to be a complicated
      heterogenous brain formation, the structure of which reflects both basic
      principles (nuclear and screen-type) of grey matter organization. Structural and
      quantitative characteristics of the amygdaloid body anterior region provides a
      confirmation for assumption that it is a nucleo-paleocortical brain component.

PMID- 9621321
TI  - [Nucleolar apparatus of proliferating and differentiating cells of human
      embryonic neocortex during formation of the cortical plate].
AB  - Human neocortex was studied using light and electron microscopy in embryos 6-10
      wks of development. Vast majority of proliferating cells was established to be
      concentrated in ventricular zone. Nuclear, nucleolar and cytoplasmic organelle
      structure indicate various level of synthetic processes activity in cells of
      different layers of the developing human neocortex. The dynamics in nucleolar
      number in the cells of ventricular zone and cortical plate was demonstrated.

PMID- 9621322
TI  - [Quantitative changes in piriform neurons of human cerebellar cortex from birth
      to 20 years].
AB  - Age changes of size parameters of piriform (Purkinje) neurons in visual
      cerebellar cortex (pyramid and lateral areas of right and left digastric lobes)
      were studied at monthly intervals (during the first postnatal year) and at annual
      intervals (since birth up to 20 yrs) using computer optic image analyzer.
      Postnatal development of piriform neurons from human cerebellar visual cortex was
      found to be periodic (cyclic); each morphological cycle is characterised by
      certain duration and a series of quantitative and qualitative changes.

PMID- 9621323
TI  - [Ultrastructural organization of cardiomyocytes in various lower vertebrates].
AB  - Electron microscopy was used to study myocardium in Cyprinus carpio, Bufo bufo
      and Lacerta agilis. Myofibrils, mitochondria, nuclei and secretory granules in
      cardiomyocytes (CMC) of atrium and ventricle were analyzed quantitatively.
      Amphibians and reptiles showed significant complication of both structural
      organization of CMC and intercellular contacts versus bony fish. The absence of T
      systems in bony fish was noted.

PMID- 9621324
TI  - [Proliferative properties of cell differons in the vascular wall].
AB  - Using quantitative methods (radioautography using thymidine label, DNA
      cytophotometry and mitotic index definition) proliferative properties of the
      vascular wall main cell differons (endothelium, smooth myocytes and fibroblasts)
      were investigated in 60 rats during postnatal and reparative morphogenesis. Most
      pronounced DNA synthesis was noted to occur in aortal endothelium in newborn
      animals and in fibroblasts of adventitia in 1 and 6 months and old aged (2.5
      years) rats. In various vessel types of adult animals significant differences of
      label incorporation in fibroblasts of adventitia were not revealed whereas
      endothelial daily proliferation pool varies significantly showing minimal value
      (0.5%) in inferior caval vein and maximal (6%)-in capillaries. During the
      regenerative morphogenesis of aorta, caused by adventita cryodestruction
      proliferative activity elevation was noted in all the cell types, most reactive
      of them being smooth myocyte differon of the media.

PMID- 9621325
TI  - [Pathways of tissue fluid transport].
AB  - Mesenteries, cornea, lens and costal cartilages, nourished, as it is commonly
      believed, diffusely, were investigated by dye injection into vascular bed, and
      using luminescent and electron microscopy. The presence of regular nonvascular
      microcirculation pathways (interstitial canals) providing fluid passage from
      blood vessels into interstitium and consequently through the opened
      interendothelial contacts in the lymph capillaries into the lymphatic vessels was
      found when examining jejunal mesentery. Findings on the existence of extravasal
      paths of mobile tissue fluid were obtained after examination of avascular tissue
      of cartilage, cornea and lens as well. Their presence adds to reported data on
      lymph formation and allows to reconsider such unclear items as nonvascular organ
      nutrition, deficiency of primary lymph in prenodular lymph vessels and
      experimental remodelling of elephantiasis.

PMID- 9621326
TI  - [Structure of the rat lymphoid organs after prenatal exposure to indomethacin
      during antigenic stimulation].
AB  - Primary immune response of thymus and mesenteric lymph nodes to prenatal action
      of indomethacin was studied in one month rats. Indexes of cell reactions in the
      experimental rat thymus were found to coincide with control during all phases
      although blast transformation intensity was slightly reduced. In mesenteric lymph
      nodes primary immune response was suppressed which was connected with lymphocyte
      functional insufficiency. This is manifested through less intensive intercellular
      cooperation in the first phase, suppression of blast transformation in B
      lymphocytes in the second and decrease of functional activity of the node B zones
      in the third ones.

PMID- 9621327
TI  - [Lymphoid tissue in the wall of adult human gallbladder].
AB  - Lymphoid structures of mucosa and muscular coat from the gall bladder cervix,
      body and fornix were examined in histological preparations using morphometry and
      methods of variation statistics. Lymphocyte concentration in the organ walls
      grows proportionally to age. In the first period of maturity lymphoid nodules are
      absent in mucosal lamina propria while lymphoid nodules are rarely encountered
      among the cells of the fibroblastic series. Connective tissue layers of muscular
      coat are predominant sites of lymphoid aggregations. Senescence is characterised
      by the appearance of lymphoid nodules in the gall bladder mucosa. Cell
      concentration, structure and composition per unit area depend on nodule
      localization and the age of the individual.

PMID- 9621328
TI  - [Structural features of the rat adrenal cortex with inherited stress-induced
      arterial hypertension in the early period of postnatal ontogenesis].
AB  - Comparative morphometric examination of adrenal cortex was carried out in 3 wks
      HNCAI rats with inherited stress induced arterial hypertension and normotensive
      Wistar rats. Relative adrenal mass, volume of cortex and its glomerular zone in
      HNCAI rats exceeds appropriate values in Wistar rats. Increase of
      adrenocorticocytes due to hyperplasia of their ultrastructural components was
      found. In hypertensive rats adrenocorticocyte numerical density increase due to
      their hyperplasia was found in adrenal fasciculate zone in contrast to glomerular
      one. These structural organization peculiarities in 3 wks hypertensive rat
      adrenal cortex reflect their elevated functional activity and may determine
      genetically programmed increased organism responsiveness to stress that
      consequently provides the grounds for the hypertensive status formation in this
      rat line.

PMID- 9621329
TI  - [Endocrine apparatus of the epithelium of small intestinal mucosa of Rana
      temporaria].
AB  - By methods of light and electron microscopy and histochemistry endocrinocytes of
      mucosal epithelium of small intestine were studied in Rana temporaria in June.
      Middle part of small intestine contains maximum number of endocrinocytes per 1 mm
      of mucosa. Electron microscopic study revealed 7 types of endocrinocytes, EC
      cells being the most numerous one. In the aspect of endocrinocyte identification
      endocrine apparatus of rana temporaria small intestine epithelium can be compared
      with that of mammals despite peculiarities of the epithelial layer structural
      organization.

PMID- 9621330
TI  - [Reconstructive model of organs of the embryonal retroperitoneal space].
AB  - Data on formation of organocomplexes in retroperitoneal space (gonadomesonephric,
      adreno-renal and pancreatoduodenal) and dynamics of their topographo-anatomic
      interrelations during human intrauterine development are presented.

PMID- 9621331
TI  - [Morphofunctional characteristics of interstitial endocrine cells (Leydig cells)
      from testis and prostate of Orenburg goats in ontogenesis and under conditions of
      seasonal changes in their reproductive activity].
AB  - Dynamics of structural reorganizations of goat testicular Leydig cells and
      prostate was monitored in different periods of ontogenesis using light and
      electron microscopy. Morphological equivalents of endocrinocyte functional
      activity elevations were noted within the period from d 60 to 70 of
      embryogenesis, at puberty and in mature animals before the onset of mating period
      in mature animals. Endocrinocyte foetal population destruction occurs by the 1st
      postnatal month. Leydig cell maximum activity peak precedes structural and
      functional differentiation in prostate both at stages of ontogenesis and in
      periods of seasonal oscillations of reproductive activity.

PMID- 9621332
TI  - [Tissue organization and development of the choroid plexus in the human brain].

PMID- 9621333
TI  - [Medical trend in the teaching of histology, cytology and embryology].

PMID- 9621334
TI  - [Optimization of test control of science in the department of histology].

PMID- 9621335
TI  - [Histogenetic analysis of tissue variability and regeneration (a scientific
      meeting, Saint-Petersburg, April, 1997)].

PMID- 9621336
TI  - [International conference on microcirculation].

PMID- 9621337
TI  - [92nd Congress of the International Scientific Society "Anatomische
      Gesellschaft", in association with the Congress of the Polish Anatomic Society].

PMID- 9621338
TI  - [The work of the Cabardino-Balcarian Section of the All-Russian Scientific
      Society of anatomists, histologists and embryologists during 1996].

PMID- 9621339
TI  - [Report on the work of the editorial board of the journal "Morphology" in the
      year 1997].

PMID- 9621340
TI  - Imbalances of trace elements related to oxidative damage in Alzheimer's disease
      brain.
AB  - Four elements that have been implicated in free-radical-induced oxidative stress
      in Alzheimer's disease (AD) were measured by instrumental neutron activation
      analysis (INAA) in seven brain regions from 58 AD patients and 21 control
      subjects. A statistically significant elevation of iron and zinc was observed in
      multiple regions of AD brain, compared with controls. Mercury was elevated in AD
      in most regions studied, but the high variability of mercury levels in both AD
      and control subjects prevented the AD-control difference from reaching
      significance. Selenium, a protective agent against mercury toxicity, was
      significantly elevated only in AD amygdala. The elevation of iron and zinc in AD
      brain has the potential of augmenting neuron degeneration through free radical
      processes.

PMID- 9621341
TI  - Drug metabolism in in vitro organotypic and cellular models of mammalian central
      nervous system: activities of membrane-bound epoxide hydrolase and NADPH
      cytochrome P-450 (c) reductase.
AB  - The membrane-bound form of epoxide hydrolase and NADPH-cytochrome P-450 (c)
      reductase are two important enzymes involved in the bioactivation/bioinactivation
      balance of cerebral tissue. In vivo, the developmental profiles and regional
      localizations of these two enzymes were investigated in the rat. The regional
      distribution study showed that they are ubiquitously present among the major
      brain structures. Both enzyme activities were present in the brain prior to
      birth, and hence tissue from early developmental stages is suitable to develop in
      vitro cellular or organotypic models for toxicity studies involving these
      metabolic pathways. Because various neurotoxicological effects can be dependent
      on spatio-temporally regulated cell-cell interactions, we aimed to employ
      organotypic tissue cultures in which the cytoarchitecture was well preserved. In
      such cultures, the temporal expression profiles of epoxide hydrolase and NADPH
      cytochrome(c) P-450 reductase reflected the in vivo situation. The technically
      less demanding pure neuronal and glial cell cultures were also investigated.
      Detoxification of benzopyrene-4,5-epoxide and superoxide production arising from
      the reductive metabolism of various drugs were determined in all three systems.
      The results indicate that though organotypic culture is a good model for the
      metabolic pathways studied, less complicated single cell cultures can also
      represent appropriate model systems, providing that the expression of the enzymes
      involved has been first established in these systems. NADPH-cytochrome P-450
      reductase-dependent metabolism is active in both neuronal and glial cells,
      whereas the detoxification of reactive epoxides occurs mainly in glia.

PMID- 9621343
TI  - Analysis of chemically-induced alterations of the motor activity in rats.
AB  - A computerized method for the evaluation of behavioral responses induced by
      neurotoxicants in rats is described. A dynamic image analysis system was adapted
      for the measurement of the duration, vigor and averaged velocity of motor
      activity (locomotor or not) of behavioral responses induced chemically in rats.
      Three known animal models of epilepsy: systemic administration of kainic acid,
      pentylenetetrazole and 4-aminopyridine were used for reference. The method, based
      on the concurrent measurement of the quantity and quality of the movements,
      allowed the systematic evaluation of the behavior patterns induced. Three
      different levels of analysis were used. Firstly, we measured the time spent by
      the animal performing physical movements during long successive intervals (30
      min) of the test, a motor activity analysis similar to that obtained with other
      motor activity recording devices. Secondly, the system was designed to
      distinguish movements energetically or forcefully performed by the animal
      according to a previously defined vigor level and then we determined the presence
      of vigorous and non-vigorous activity throughout the test at 2 min interval.
      Finally, we applied the method to perform a more detailed analysis of the motor
      characteristic of behavioral components exhibited by the animals determining the
      velocity and vigor of movements over short intervals of time (5 sec). Thus, motor
      activity profiles, the vigor of the motor responses and the description of
      behavioral components were used for the comparative analysis of behavior induced
      by the aforementioned convulsant agents.

PMID- 9621342
TI  - Valproic acid, but not its non-teratogenic analogue 2-isopropylpentanoic acid,
      affects proliferation, viability and neuronal differentiation of the human
      teratocarcinoma cell line NTera-2.
AB  - The antiepileptic drug valproic acid (VPA) is an established human teratogen that
      affects neural development in human fetuses exposed to the drug during early
      pregnancy. The development of simple cell culture models that reflect normal
      neuronal development will be useful for the screening of neural developmental
      toxicity of new drugs and for the identification of the specific molecular
      targets for the teratogenic action. The present study tests a human NT2 cell line
      for its suitability to serve as such a model. Treatment with VPA, but not with
      its non-teratogenic-analogue, 2-isopropylpentanoic acid (IPPA), inhibited cell
      growth, had a cytotoxic effect and blocked retinoic acid-induced neuronal
      differentiation of NT2 cells. Differentiation was evaluated by immunostaining for
      neurofilament proteins, microtubule associated proteins-2 (MAP-2), tau and neural
      cell adhesion molecule, NCAM. However once differentiation had taken place, VPA
      did not revert this process, although it did affect neuronal aggregation and
      neurite fasciculation. These results suggest that the human NT2 cell line might
      be useful for identifying drugs affecting neuronal development in humans.

PMID- 9621344
TI  - Neural lesions in the rat and their relationship to EEG delta activity following
      seizures induced by the nerve agent soman.
AB  - This study describes the neural structures damaged following exposure to the
      nerve agent soman, shows there are time-dependent differences in the extent of
      damage in certain structures, and relates seizure-induced increases in delta band
      (0-3.5 Hz) electroencephalographic (EEG) activity with severity of subsequent
      neuropathology. Rats, instrumented to record cortical EEG activity, were
      pretreated with the oxime HI-6 (125 mg/kg, i.p.) and then challenged with soman
      (180 ug/kg, s.c.). All animals developed continuous epileptiform seizures that
      lasted in excess of 4 hr. Groups of animals were perfused 1, 3, 10 or 30 days
      following exposure. Paraffin-embedded brains were stained with hematoxylin and
      eosin; thirty-four neural structures were examined and scored for neural damage.
      All cortical areas sustained damage, with piriform and perirhinal cortices
      exhibiting the most severe. Subcortical limbic areas (amygdala, amygdala-piriform
      transition zone, hippocampus, claustrum) and various thalamic nuclei were most
      consistently and severely damaged in all animals regardless of survival time.
      Brainstem structures, cerebellum, spinal cord, and other motor output nuclei were
      never damaged. It was found that some structures were rated as more severely
      damaged when evaluated at shorter survival times. Severity of neural damage was
      related to high levels of EEG delta power recorded 24 hr after exposure; power
      during the acute seizure or 24 hr body weight loss did not predict lesion
      severity. Sections between AP -0.8 to -4.8 contain cortical and subcortical
      structures that can be readily and reproducibly evaluated for brain damage.

PMID- 9621345
TI  - Morphological and immunocytochemical effects of dihydroartemisinin on
      differentiating NB2a neuroblastoma cells.
AB  - The toxicity caused by the artemisinin derivative dihydroartemisinin in
      differentiated NB2a neuroblastoma cells was studied by transmission and scanning
      electron microscopy, Western blotting and immunocytochemistry. Western blotting
      with monoclonal antibodies failed to detect any specific changes in the cell
      cytoskeleton, nor were any changes detected by immunocytochemistry. This was
      consistent with electron microscopy of surviving cell neurites. Transmission
      electron microscopy revealed that dihydroartemisinin damaged NB2a cell
      mitochondrial cristae and endoplasmic reticulum. Scanning electron microscopy
      revealed that dihydroartemisinin depleted the filopodia-like processes projecting
      from the surface of the cell body and neurites. Some, or all, of these drug
      induced changes in differentiating NB2a cells may have a role in the
      neurotoxicity of artemisinin derivatives.

PMID- 9621346
TI  - Binding of dihydroartemisinin to differentiating neuroblastoma cells and rat
      cortical homogenate.
AB  - The binding characteristics of dihydroartemisinin to neural tissues and cells in
      culture were studied by incubating differentiating C6 and NB2a cells and rat
      cerebral cortex homogenate with 1 to 200 microM 14C-labelled dihydroartemisinin
      with or without 2 microM haemin for 24 h. The role of protein thiol and amine
      groups in dihydroartemisinin binding was assessed by pre-incubation of the cortex
      homogenate with sodium cyanate and/or iodoacetamide. Rosenthal plots of binding
      data demonstrated that there were two discrete phases of dihydroartemisinin
      binding. Haemin increased the total binding of dihydroartemisinin to both cortex
      and cell proteins. In each preparation, haemin increased Bmax of the high
      affinity binding sites and also increased kD of NB2a high affinity binding sites
      and decreased kD of cortex low affinity binding sites. The effects of haemin on
      the binding parameters of cortex resembled its effects on C6 cells rather than
      NB2a cells. NB2a high and low affinity binding sites had a greater affinity for
      dihydroartemisinin than those of either rat cortex or C6 cells. Iodoacetamide and
      sodium cyanate reduced binding to cortex proteins by approximately 70%. Co
      incubation of 14C-dihydroartemisinin with arteether reduced binding of
      dihydroartemisinin but co-incubation with desoxyartemisinin did not. These
      studies demonstrate that the known haemin-induced increase in toxicity of
      dihydroartemisinin to differentiating neuroblastoma cells is accompanied by a
      corresponding increase in dihydroartemisinin binding to cell proteins, that
      protein thiol and amine groups react with the products of the reaction between
      dihydroartemisinin and haemin and point to a relationship between the toxicity of
      artemisinin derivatives and protein binding.

PMID- 9621347
TI  - Diminished blocking effect of acute lead exposure on high-threshold voltage-gated
      calcium currents in PC12 cells chronically exposed to the heavy metal.
AB  - Rat pheochromocytoma (PC12) cells were grown in 0, 10, 25, or 50 microM lead
      containing growth media for up to twelve weeks. High-threshold whole-cell calcium
      currents from these PC12 cells were recorded in lead-free recording media
      (control), then in 1 microM lead-containing recording media (acute challenge),
      and finally again in lead-free recording media (wash). The acute lead challenge
      decreased calcium currents in all treatment groups (including 0 microM lead).
      However, this blocking effect of acute lead application diminished with prolonged
      chronic exposure to 25 and 50 microM lead. Although the acute lead challenge
      mainly caused a decrease in calcium currents, in some chronically exposed PC12
      cells increased calcium currents were recorded during the application of 1 microM
      lead acetate. In other chronically exposed PC12 cells, the acute lead challenge
      caused the peak of the current-voltage curve to shift from +10 mV to 0 mV. The
      number of cells exhibiting either an increase in calcium current or a shift in
      the current-voltage relationship following acute lead challenge increased with
      prolonged chronic exposure to the heavy metal. The time-dependent increase in
      calcium influx may be responsible for at least one manifestation of lead
      neurotoxicity.

PMID- 9621348
TI  - Initial sensorimotor and delayed autonomic neuropathy in acute thallium
      poisoning.
AB  - In a 27-year old male with acute thallium poisoning, signs of initially severe
      sensorimotor neuropathy with complete remission after two weeks were
      demonstrated. Signs of cardiovascular autonomic neuropathy were initially absent,
      but developed after a latency period of one week with marked improvement after
      seven months. Delayed autonomic neuropathy may be caused by a late affection of
      small unmyelinated autonomic nerve fibers.

PMID- 9621349
TI  - An integrated hypothesis for the serotonergic axonal loss induced by 3,4
      methylenedioxymethamphetamine.
AB  - Administration of the street drug 3,4-methylenedioxymethamphetamine (MDMA) to
      various experimental animals has been shown in several laboratories to induce
      selective damage to serotonergic axons and axon terminals. This review examines
      the current available evidence supporting the development of serotonin (5-HT)
      neurotoxicity in animals and humans. There are a plethora of hypotheses that
      attempt to explain the mechanisms involved in the development of this
      serotonergic neurotoxicity. An integrated hypothesis incorporating most of the
      speculated neurotransmitters theorized to be involved in the process is proposed.
      This hypothesis states that MDMA induces the following sequence of events
      resulting in the serotonergic neurotoxicity: 1. MDMA induces an acute release of
      5-HT and dopamine (DA). 2. This acute release is followed by depletion of
      intraneuronal 5-HT stores. 3. The initially released 5-HT activates post-synaptic
      5-HT2A/2C receptors located on GABA interneurons resulting in a decrease in
      GABAegic transmission and increased DA release and synthesis. 4. The excessive DA
      released then may be transported into the depleted 5-HT terminal. 5. The DA is
      then deaminated by monoamine oxidase B (MAO-B) located within the 5-HT terminal.
      This results in free-radical formation and the selective degeneration of the
      serotonergic axons and axon terminals. While there is no clear evidence that
      human users of the drug are suffering a similar neurotoxicity, data are presented
      suggesting that there remains cause for concern.

PMID- 9621350
TI  - [Neurosurgery and molecular biology: (series 3) molecular biology of the brain
      neurons].

PMID- 9621351
TI  - [Functional three-dimensional brain image].

PMID- 9621352
TI  - Trigeminal neuralgia caused by the metastasis of malignant lymphoma to the
      trigeminal nerve: a case report.
AB  - The authors cared for a patient suffering from left trigeminal neuralgia who had
      systemic malignant lymphoma which had been treated with chemotherapy. The lesion
      of the left trigeminal nerve was not detected by brain CT scans or by the
      magnetic resonance images made at the onset of trigeminal neuralgia. However,
      metastasis to the left trigeminal nerve root was disclosed 6 months after the
      onset of the systemic lymphoma. Open biopsy confirmed lymphomatous involvement of
      the left trigeminal nerve root. In this case the site of the metastasis was
      mainly the trigeminal nerve root entry zone in the cerebellopontine cistern, and
      the lesion caused left trigeminal neuralgia and sensory impairment.

PMID- 9621353
TI  - [Neonatal intracranial tumor highly suspected of teratoma in the lateral
      ventricle consisting of multiple cysts: case report].
AB  - Neonatal intracranial teratoma is rare and early attempts at surgical treatment
      are not usually successful. We describe an exceptionally rare case of neonatal
      intracranial tumor in the lateral ventricle composed of multiple cysts with
      little mass content which was highly suspected of teratoma and treated
      successfully by microsurgery. A 55-day-old male was admitted to our hospital with
      complaints of convulsive seizure. Examination found no obvious neurological
      deficit except mild enlargement and bulging of anterior fontanel. There were no
      abnormal laboratory findings. Computerized tomography with contrast medium
      revealed an 8 cm multicystic lesion with little mass content in the right lateral
      ventricle and hydrocephalus. Magnetic resonance imaging showed the cystic content
      as slightly higher in intensity than CSF on the T1-weighted image and of higher
      intensity than CSF on the T2-weighted image. The cyst wall was enhanced on T1
      weighted image with gadolinium. The aqueduct was obstructed by compression due to
      the intraventricular cyst. A right occipitoparietal craniotomy was performed,
      which disclosed a hair in the cyst wall, two huge cysts, and independence of the
      intracystic lesion from the lateral ventricle. The tumor was removed except for a
      small part adjacent to the pineal region, from which the tumor had presumably
      originated. Mature teratoma was highly suspected on the basis of the hair in the
      cyst wall and histological examination of the specimen, which revealed
      hamartomatous tissues derived from two germ cell layers. After surgery, his
      hydrocephalus was improved and convulsive seizures were reduced remarkably. He
      was discharged ten days later and is being followed up. Reoperation will be
      performed if regrowth of the residual tumor occurs.

PMID- 9621354
TI  - [Perforation of the bladder by a peritoneal catheter: an unusual late
      complication of ventriculo-peritoneal shunt].
AB  - Late perforation of the bladder by an abdominal catheter of a
      ventriculoperitoneal (VP) shunt is extremely rare. We report the successful
      treatment of a patient who presented with this complication. An 82-year-old woman
      received a V-P shunt for normal pressure hydrocephalus following subarachnoid
      hemorrhage. Ten years later she was admitted to our hospital with neck pain. A
      few days after admission, the tip of the peritoneal catheter was found to be
      protruding from the urethra during urination. Subsequently, the patient developed
      meningitis. Contrast study of the distal tubing demonstrated the continuity of
      the peritoneal shunt tube. After the entire system was removed, antibiotic
      treatment was administered for 2 weeks. and a new VP shunt was placed on the
      opposite side. The post-operative course was uneventful. Previous reports
      regarding complications after the placement of a VP-shunt show that periodic
      chest and abdominal X-ray studies are important. In this case, however, the
      peritoneal tube was not able to be observed on abdominal plain film. For this
      reason, an unfaded radiopaque tube is necessary if there is to be early diagnosis
      of late organic perforation by a peritoneal shunt tube.

PMID- 9621355
TI  - [A case of bow hunter's stroke caused by bilateral vertebral artery occlusive
      change on head rotation to the right].
AB  - We report a case of bow hunter's stroke caused by simultaneous bilateral
      vertebral artery occlusive changes at the right C3-4 and the left C1-2 level on
      head rotation to the right side. The pathogenesis and surgical treatment for this
      particular case are discussed. A 61-year-old male with cervical spondylosis
      repeatedly experienced vertebrobasilar insufficiency when he rotated his head
      over 60 degree from the mid-position to the right side. Bilateral vertebral
      angiography demonstrated severe compression of the right vertebral artery by a
      lateral osteophyte and instability at the C3-4 level accompanied with the
      mechanical stenosis of the left vertebral artery at the C1-2 level only at the
      time of turning his head to the right. As the surgical treatment we performed
      osteophytectomy of the right uncovertebral joint at the C3-4 level in addition to
      anterior decompression with fusion using hydroxyapatite spacer and titanium plate
      at that level. Postoperatively, the patient had no ischemic episodes and there
      was angiographical resolution of the rotational stenosis at the C3-4 level. For
      the clinical manifestation of bow hunter's stroke on head rotation, it is
      indispensable that simultaneous severe occlusive changes present on bilateral
      vertebral arteries. In case of a vertebral occlusive change caused by lateral
      osteophyte at the unstable vertebral joint, anterior decompression and fusion
      with osteophytectomy may be a wiser approach than arterial decompression or
      posterior fusion at the C1-2 level to another vertebral artery occlusive lesion.

PMID- 9621356
TI  - [A case of traumatic subacute subdural hematoma presenting symptoms arising from
      cerebral hemispheric edema].
AB  - Traumatic subacute subdural hematoma is a condition in which the major symptoms
      affecting prognosis most appear in the subacute stage after head trauma, while
      traumatic acute subdural hematoma is treated conservatively when the symptoms are
      mild. The cause of the major symptoms occurring in the subacute stage is mostly
      expansion of the subdural hematoma volume. The authors report a case of traumatic
      subacute subdural hematoma in which the cause of the major symptoms was cerebral
      hemispheric edema instead of expansion of the subdural hematoma volume. To our
      knowledge, only one similar case to the present case has been previously
      reported. A 44-year-old female fell from the stairs on July 21, 1995 and was
      suffering from headache. On July 23, she was admitted to our hospital because of
      generalized convulsion. On admission, she was drowsy but showed no convulsion.
      Head CT showed an acute subdural hematoma on the right side with a slight midline
      shift and no other abnormalities. She was treated conservatively because of the
      mildness of the symptoms and two days later became alert with no symptoms.
      Thereafter she only complained of occasional headache which was controlled with
      medicine. On August 3, she suddenly fell into coma. Head CT showed severe
      cerebral hemispheric edema on the right side without change of the subdural
      hematoma size. Emergency cerebral angiography showed no definitive abnormalities
      such as occlusion of the arteries or of the venous sinuses. Craniotomy associated
      with external decompression was performed. The hematoma was composed of red-brown
      jelly accompanied with some liquid component and had a thin black-brown outer
      membrane. While removing the hematoma, bleeding from a vein on the cerebral
      surface around the sylvian fissure was observed and this location was suspected
      to be the sources of the bleeding point. Postoperatively, she received steroid
      and barbiturate therapy associated with moderate hypothermia under
      hyperventilation. She tolerated this treatment well and left the hospital, on
      September 26, 1995 with only diplopia during downward gaze. Although the
      mechanisms of the cerebral hemispheric edema occurring in the subacute stage was
      unclear, a failure in the cerebral venous circulation arising from compression to
      the bridging veins, which may be hypoplastic, by the subdural hematoma was
      suspected to have been the cause.

PMID- 9621357
TI  - [A case of agraphia due to cerebral infarction in the left parietal lobe].
AB  - A case of agraphia due to cerebral infarction in the left parietal lobe was
      reported. A 63-year-old right-handed man was admitted to our hospital with
      writing disturbance. His spontaneous speech was fluent, and object naming, word
      fluency, repetition, verbal comprehension, and reading were fully preserved.
      However, his writing was slow and required effort. He showed hesitation in
      spontaneous writing and dictation. His power to copy was better than his power to
      write spontaneously or to take dictation, but he had some difficulty in copying
      letters and complex figures. The patient showed abnormal sequences of strokes and
      completed his strokes by piecing out of several fragments. CT scan and MRI showed
      a cerebral infarction in the left parietal lobe which included the superior
      parietal lobule. The amytal (Wada) test, which was performed via the left
      internal carotid artery, revealed that the left hemisphere was dominant for
      language. The characteristics of his agraphia much more closely resembled
      "apractic agraphia", as reported by Alexander et al (1992), than spatial agraphia
      or pure agraphia. Agraphia in this patient might result partially from the loss
      or unavailability of the memory of motor patterns necessary for writing letters.

PMID- 9621358
TI  - [A case of rhinocerebral mucormycosis presenting orbital apex syndrome].
AB  - A 62-year-old man with untreated diabetes complained of diplopia and headache.
      Neurological examination demonstrated left abducens nerve palsy. MRI showed a
      mass lesion in the left orbital apex. Total left ophthalmoplegia and visual loss
      rapidly developed in the next two weeks. A craniotomy was performed to decompress
      the orbital apex and remove the mass. The optic nerve was tightly encased by
      fibrous tissue. The pathological diagnosis was mucormycosis. Systemic
      administration of amphotericin B and fluconazole was started immediately. But the
      lesion rapidly invaded the cavernous sinus and occluded the left internal carotid
      artery. Finally, the patient died with intracranial extension of mucormycosis
      four months after the operation. Rhinocerebral mucormycosis is a rapidly
      progressive fatal disease. Successful treatment seems to be based on early
      diagnosis, control of the underlying disease, radical surgical resection, and
      systemic administration of amphotericin B. Mucormycosis should be considered as a
      differential diagnosis of orbital apex syndrome.

PMID- 9621359
TI  - [Epstein-Barr virus-associated malignant lymphoma in an immuno-deficiency
      patient: a case report].
AB  - Human infection with Epstein-Barr (EB) virus occurs commonly, and EB virus exists
      in the B cell as a cryptic infection. Infected B cells become immortal by
      expressing both the EBNA2 and the LMP1 genes derived from the EB virus. Under
      normal condition of cellular immunity, the T cells recognize the EBNA2 and LMP1
      as foreign proteins and attack the immortal B cells. However, under the condition
      of immunodeficiency, the immortal B cells can proliferate and form a tumor. We
      report a case of malignant lymphoma associated with immuno-deficiency which may
      correspond to this mechanism. A 33-year-old woman, who had an immuno-deficiency
      due to treatment for leukemia, had a progressing hemiparesis on her left
      extremities. Magnetic resonance imagings revealed a ring enhanced tumor with
      massive brain edema in the right fronto-parietal lobe. Stereotactic biopsy was
      performed and histological examination showed it to be a malignant lymphoma. The
      tumor cells were positive for L26 (B cell marker), CD79a LMP1, and EBNA2. They
      were negative for UCHL-1 and CD3 (T cell marker). According to these results,
      this lymphoma was caused by EB virus infection under the condition of immuno
      deficiency.

PMID- 9621360
TI  - [Two cases of mesial temporal lobe epilepsy associated with old intracerebral
      hemorrhage in the lateral temporal lobe without "dual pathology"].
AB  - Two cases of intractable temporal lobe epilepsy associated with old intracerebral
      hemorrhage in the lateral temporal lobe were reported. Although preoperative
      magnetic resonance imaging (MRI) failed to reveal hippocampal atrophy with T2
      hyperintensity, electrocorticographic (ECoG) recording with chronic invasive
      subdural electrodes indicated the mesial temporal lobe to be an ictal onset zone.
      After anterior temporal lobectomy involving the lesion and hippocampectomy, the
      patients became seizure-free. Hippocampal sclerosis, namely "dual pathology", was
      not noted on histological examination. Careful ECoG recording with chronic
      subdural electrodes is mandatory even when the preoperative MRI does not
      demonstrate the radiological hippocampal sclerosis.

PMID- 9621362
TI  - [Japanese version of the Short-Memory Questionnaire: memory evaluation in
      Alzheimer's disease].
AB  - BACKGROUND AND PURPOSE: Memory deficit is a common sign of Alzheimer's disease
      (AD), which appeared generally in the early stage of the disease. Therefore,
      evaluation of memory is important for management of patients and for clinical
      research of AD. The Short-Memory Questionnaire (SMQ), an easily administered,
      informant-based scale, which was developed by Koss et al. (1993), is a
      standardized, validated, and reliable tool to assess everyday memory problems. In
      the present study, we prepared a Japanese version of the SMQ and examined its
      reliability and validity in assessing AD patients. SUBJECTS AND METHODS: The
      subjects consisted of 42 patients with NINCDS-ADRDA probable AD whose diagnosis
      was made on the basis of the results of comprehensive examinations including
      cranial CT/MRI and SPECT and age- and education-matched 53 healthy controls.
      Patients had no history of stroke, head injury, or any other prior neurological
      events. Patients and controls were between the ages of 51 and 90 years, and they
      had from 6 to 16 years education. The Japanese version of the SMQ was given to a
      family member by either neuropsychiatrist, public nurse or case worker. To
      evaluate test-retest reliability of the test, interview was repeated in 16
      randomly selected patients by two different examiners (neuropsychiatrist and
      another) in two weeks interval. The Mini-Mental State Examination (MMSE) was used
      to assess the severity of cognitive impairment. RESULT: The test-retest
      reliability was acceptably high with intraclass correlation coefficients. There
      was a high correlation between scores of SMQ and MMSE. The SMQ had excellent
      specificity and sensitivity in discriminating patients from controls. Caregiver
      appraisals of memory deficits significantly correlated with generalized cognitive
      dysfunction. CONCLUSIONS: Similarly to the original version, the present Japanese
      version of the SMQ is a reliable and valid tool in assessing memory function in
      AD, which can be effectively used in clinical settings and epidemiologic studies
      to screen out persons with memory problems.

PMID- 9621361
TI  - [Induction of apoptosis through NGF/p75NTR in human glioma cells treated with
      propentofylline].
AB  - Propentofylline (PPF) is a xanthine derivative and it has been reported that PPF
      stimulated the synthesis/secretion of nerve growth factor (NGF) by cultured
      astroglial cells. We have reported that PPF induced apoptosis in human glioma
      cells and as its mechanism, up-regulation of NGF, Fas, Bax beta and down
      regulation of Bcl-2 were assumed. Recent studies demonstrated the presence of
      apoptosis induced via NGF/p75NTR in developmental neuron, oligodendroglia. In the
      present study, to examine whether signal cascade via NGF/p75NTR participates the
      apoptosis in human glioma cells treated with PPF, we investigated the
      immunohistochemical study using anti-mouse monoclonal antibody,
      immunoprecipitation and northern blot analysis for p75NTR, NF-kappa B in human
      glioma cells (U251MG, T98G, U87) treated with PPF. We observed the up-regulation
      of p75NTR, translocation of NF-kappa B to the nucleus after treatment with PPF in
      these cell lines. According to above results, it is assumed that apoptosis in
      human glioma cells treated with PPF was induced via NGF/p75NTR.

PMID- 9621363
TI  - [A lateralized reduction of NAA in a case of corticobasal degeneration (CBD):
      application of proton magnetic resonance spectroscopy (1H-MRS)].
AB  - We studied the application of proton magnetic resonance spectroscopy (1H-MRS) in
      a case of corticobasal degeneration. A 73-year-old woman was referred to our
      hospital for dysarthria and clumsiness in right arm movement. Intelligence was
      normal and neither ideational apraxia or ideomotor apraxia were observed. Her
      speech was slurred and extremely slow. Neurological findings showed a limitation
      of ocular upward gaze movement, impaired smooth pursuit in the horizontal gaze,
      rigidity, limb kinetic apraxia and cortical sensory disturbance in the right arm.
      Magnetic resonance imaging (MRI) showed diffuse brain atrophy, especially in the
      left fronto-parietal cortex around the central sulcus. A positron emission
      tomography (PET) study showed diffuse decrement of cerebral blood flow,
      dominantly in the left hemisphere. The decrease in the uptake of 18F-Fluoro
      deoxyglucose also revealed glucose hypo-metabolism, especially in the left
      frontal and parietal lobe. 1H-MRS by the multivoxel method showed a decrease in N
      acetylaspartate (NAA)/Creatine to 1.0 in the left basal ganglia and temporal
      lobe, compared to the values between 1.4 and 1.7 in the right basal ganglia.
      These findings indicated that 1H-MRS might detect neuronal loss or degeneration
      when MRI showed minimal cortical atrophy. This study, the first application of 1H
      MRS in a case of corticobasal degeneration, showed that this method was useful
      for the evaluation of pathophysiological changes in corticobasal degeneration.

PMID- 9621364
TI  - [Endoscopic third ventriculostomy in a case of obstructive hydrocephalus with
      neurofibromatosis (NF-1)].
AB  - Endoscopic third ventriculostomy in a case of obstructive hydrocephalus with
      neurofibromatosis (NF-1) was reported. The patient was a 25-year-old male, who
      suffered from progressive headache and somnolence. He underwent a
      ventriculoperitoneal shunt at the age of 11 years. After that, 8 times of shunt
      revision and unilateral subtemporal decompression were performed during 14 years
      until this admission. The programmable valve system was used at the last
      procedure. On admission, computed tomography (CT) scan showed marked enlarged
      lateral and third ventricles. The patient was diagnosed as hydrocephalus
      resulting from shunt malfunction. An endoscopic third ventriculostomy was
      performed and his symptoms improved immediately. The size of the lateral and
      third ventricles was revealed normal on the CT 18 months after the third
      ventriculostomy.

PMID- 9621365
TI  - [Clear cell ependymoma--a case report].
AB  - A case of intraaxial clear cell ependymoma is reported. A 46-year-old man
      complained of right hemiparesis. CT scan showed a mass lesion on the median plane
      with a huge cyst in the left frontal lobe. MRI showed an iso-low intensity mass
      by T1-weighted image. The tumor was heterogeneously enhanced by Gd-DTPA and the
      wall was enhanced as well. Angiogram revealed a tumor stain from the right
      internal carotid artery. The main mass of the tumor was totally removed but the
      cystic wall was left removed. Histopathological examination revealed clear cell
      ependymoma. Immunohistochemical examination revealed that, although vimentin and
      NSE were positive, GFAP, synaptophysin and S-100 were negative. Ultrastructual
      examination revealed cilia, microvilli and desmosomal junctions. The patient
      fully recovered after operation and showed no sign of recurrence after an year of
      follow-up. Clear cell ependymoma is a rare variant of ependymoma. Ultrastructual
      examination was more useful than immunohistochemical examination for diagnosis.

PMID- 9621366
TI  - [The significance of the cerebellar tonsillar herniation on the cause of sudden
      death of ruptured cerebral aneurysm].
AB  - We experienced a case with sudden unexpected death caused by rupture of an
      intracranial aneurysm, which was confirmed by autopsy. Depending on this case, we
      reported the significance of the cerebellar tonsillar herniation on the cause of
      sudden death of ruptured cerebral aneurysm. A 58-year-old man was admitted to us
      for treatment of subarachnoid hemorrhage (SAH). The CT scanning showed diffuse
      SAH in the whole cistern. Cerebral angiography on admission revealed an aneurysm
      at the bifurcation of the left middle cerebral artery in association with bleb
      like configuration. The aneurysmal neck was clipped on the day of admission. The
      postoperative course was uneventful. In the early morning of postoperative 23rd
      day, he was found being expired. To clarify the cause of death, an autopsy was
      done, disclosing diffuse SAH in association with tonsillar herniation more marked
      on the left. Thus, the distortion of the spinomedullary junction due to
      asymmetrical herniation was considered to be responsible for unexpected sudden
      death in this case. Examination of the major cerebral artery disclosed a ruptured
      anterior communicating artery aneurysm.

PMID- 9621367
TI  - [A case of subarachnoid hemorrhage complaining of deafness].
AB  - A 64-year-old female came to our department because of a sudden onset of
      bilateral deafness 2 days before. She had sudden onset of mild headache, nausea
      and vomiting 9 days before, but was diagnosed as food poisoning by her home
      doctor. Her symptoms disappeared on the following day. Neurological examination
      revealed bilateral deafness, right facial palsy of central type and very slight
      neck stiffness. CT showed inconspicuous subarachnoid hemorrhage, but lumber
      puncture revealed definite subarachnoid hemorrhage. Another important finding of
      CT was old left temporal lobe infarction. Cerebral angiography detected right
      middle cerebral artery aneurysm at the trifurcation and moderate cerebral
      vasospasm of the right M2 portion. Neck clipping was successfully performed, but
      small size of right temporal lobe infarction was found on postoperative CT, which
      was due to cerebral vasospasm. Postoperative MRI showed bilateral temporal lobe
      infarction, especially including bilateral auditory cortex. This finding suggests
      that her deafness was cortical in origin.

PMID- 9621368
TI  - [Spontaneous spinal epidural hematoma with spontaneous remission, diagnosed in
      MRI on superacute stage].
AB  - We report a case of spontaneous spinal epidural hematoma with spontaneous
      remission diagnosed by MRI on superacute stage. A 52-year-old man was admitted to
      our hospital because of severe shoulder-neck-back pain of acute onset. One hour
      after onset he had left hemiparesis and gradually became tetraparesis. He had no
      history of trauma, anticoagulant therapy, or a tendency to bleed. There was no
      abnormality in the laboratory data. CT scan of the head revealed no abnormality,
      but the scan of cervical region showed an abnormal high-density area in the left
      posterior region of spinal cord at C4-C7. MRI demonstrated an epidural mass
      lesion in the left posterior region of spinal cord at C3-Th3 compressing the left
      side of spinal cord posteriorly was iso-intensity on the T1-weighted image and
      high-intensity on the T2-weighted image. However, his motor function recovered
      almost completely without a slight motor weakness of left upper limb about two
      hours after onset spontaneously. He was initially treated with a corticosteroid
      agent, and he could walk next day after onset. After about 2 weeks of onset, MRI
      revealed a vanished epidural hematoma and no abnormal enhancement. After about 2
      months of onset, spinal angiograms revealed no vascular anomaly. The mechanism of
      spontaneous recovery from tetraparesis is assumed that the spreading of hematoma
      in epidural space up- and downwards to the rostro-caudal direction results in
      decompression. MRI is useful to detect spinal epidural hematoma safely and
      accurately for its diagnosis. MRI is also proved to be an accurate and
      efficacious method for evaluation of its size, location, and extent in the spinal
      canal.

PMID- 9621369
TI  - [Langerhans cell histiocytosis in the hypothalamus: a case report].
AB  - A case of Langerhans cell histiocytosis (LCH) in the hypothalamus is presented. A
      52 year old man with eosinophilic granuloma of the lung was referred to our
      hospital. He complained of headache, easy fatigability, high fever, and voiding
      large quantities of urine, but was otherwise asymptomatic. T1-weighted images
      demonstrated a small mass in the hypothalamus. After about six months, the mass
      had grown to 2 cm in diameter. Surgery was performed by a pterional approach and
      a biopsy specimen was collected. Light microscopic examination of sections of the
      biopsy specimen showed polymorphous cellular infiltration by histiocytic cells,
      eosinophils, neutrophils, and lymphocytes. Electron microscopy showed Langerhans
      cells and Birbeck granules in the cytoplasm. The histological diagnosis was LCH,
      multifocal type. After low-dose radiation therapy, the mass gradually decreased
      in size. The clinicopathological features, neuroradiological findings, and
      treatment are briefly discussed.

PMID- 9621370
TI  - [A case of cerebral venous angioma detected by slow velocity-encoding phase
      contrast MRA: appropriate determination of velocity encode].
AB  - We report a 86-year-old woman who has been diagnosed as cerebral venous angioma
      by slow velocity-encoding phase contrast magnetic resonance angiography (MRA).
      She had developed headache for one month. T1- and T2-weighted images showed a
      flow void sign in the right cerebellum with gadolinium enhancement. MRA using
      time-of-flight sequence revealed no abnormal vascular structures. Conventional
      phase contrast MRA (velocity encode, 40 or 60 cm/sec) did not disclose obvious
      vascular abnormalities. However, slow velocity-encoding (20 cm/sec) phase
      contrast MRA demonstrated a well-demarcated venous angioma in the right
      transverse sinus. Our results of MRAs suggest that velocity encode is a crucial
      factor for detection of venous angioma on phase contrast MRA. Slow velocity
      encoding phase contrast MRA is a beneficial tool for evaluation of venous
      malformations, such as venous angioma.

PMID- 9621371
TI  - [An autopsy case of corticobasal degeneration with predominant involvement of the
      prefrontal lobe, limbic system, and especially of the medial temporal base].
AB  - We report a case of corticobasal degeneration (CBD) with prominent degenerative
      changes in the temporal base. The patient developed parkinsonism with a marked
      tendency to fall and dementia at the age of 69. His symptoms progressively
      worsened. Finally, he was akinetic and mute and died by infection at 71 years of
      age, 32-months after the onset of his neurological symptoms. At autopsy,
      symmetrical atrophy of the prefrontal lobe was seen, yet the regions around the
      central sulci were preserved. Neuronal depletion and numerous achromatic
      ballooned neurons were found in the prefrontal lobe, cingulate and rectal gyri,
      insula, and the medial temporal base. In these regions astrocytic plaque-like
      structures and argyrophilic threads were demonstrated with Gallyas' silver stain.
      These findings were compatible with CBD and were most pronounced in the
      prefrontal lobe and the medial temporal base, more predominantly on the right
      side. In contrast, the regions around the central sulci, which were the most
      severely involved in usual cases of CBD, had only mild changes. The substantia
      nigra was atrophic and showed marked neuronal loss and occasional argyrophilic
      inclusions in the remaining neurons. No Pick body was seen. In addition, findings
      of mild Alzheimer's disease and degenerative changes in the middle portions of
      the crus cerebri were observed. Our case of CBD is notable for this atypical
      topography of degeneration.

PMID- 9621372
TI  - [An autopsied case of purulent meningitis associated with ocular flutter].
AB  - We report a 72-year-old autopsied case of purulent meningitis associated with
      ocular flutter. She was admitted to our hospital because of disturbances of
      consciousness and fever. Physical examination revealed fever, tachycardia, and
      tachypnea. Neurological examination showed disturbance of consciousness (Japan
      Coma Scale 30), agitated state, anisocoria, sluggish and fixed reaction of pupils
      to light, and nuchal stiffness. Routine blood examination showed leukocytosis,
      thrombocytopenia, positive CRP, and elevated myocardial enzymes. Cerebrospinal
      fluid revealed pleocytosis with predominant leukocytes, elevated protein, and
      decreased glucose (22% of blood glucose), and Streptococcus pneumoniae was proved
      in culture. Brain CT scan revealed no abnormal findings. Electrocardiography
      showed tachycardia, left axis deviation, and elevated ST segment in aVF, and V3
      V6. Ultrasonic echocardiography revealed slight hypokinesis of the left anterior
      wall, septum, and apex. She was diagnosed as having purulent meningitis,
      myocarditis, probable encephalitis. Thus, antibiotics, acycrovir, glycerol, and
      aspirin were administrated. But her respiration deteriorated and ocular flutter
      was observed for 15 minutes. After that, She required artificial ventilation and
      eventually died after 29 hours the admission to our hospital. Pathological
      examination revealed leukocyte accumulation in the arachnoid space of the
      derebral surface, especially frontal and parietal lobes. Uncal herniation was not
      observed. The brainstem and cerebellum were histologically within normal limits.
      These findings suggest that ocular flutter observed in this patient was caused by
      functional damage of the brainstem.

PMID- 9621373
TI  - [Sturge-Weber syndrome].

PMID- 9621374
TI  - [Pontine bleeding showing locked-in syndrome over 5 years].

PMID- 9621375
TI  - [A 45-year-old man with peripheral monocytosis and right hemiparesis].
AB  - We report a 45-year-old man with monocytosis and right hemiparesis. The patient
      suffered from an acute myocardial infarction from which he recovered completely
      when he was 42 years old. One year prior to his death, he was found to have
      increase in monocyte count (35.5% of leukocytes) in peripheral blood and
      splenomegaly; he was admitted to the hematology service of our hospital. He was
      diagnosed as having chronic myelomonocytic leukemia after bone marrow
      examination. He was treated with radiation therapy with improvement in
      splenomegaly. In May of 1995, he had fever, anemia, and thrombocytopenia for
      which he needed daily blood transfusion. In November of 1995, he had an onset of
      weakness in his right hand, and neurologic consultation was asked for in November
      27, 1995. Neurologic examination revealed a chronically ill japanese man in no
      acute distress. He was alert and not demented. Higher cerebral functions were
      intact. Cranial nerve examination revealed right facial paresis of the central
      type. Motor-wise, he was right hemiparetic. Generalized muscle wasting was noted
      apparently due to the chronic debilitating disease. Deep tendon reflexes were
      within normal range in the right upper extremity, but were diminished in other
      areas. Sensation was intact, and no meningeal signs were noted. Pertinent
      laboratory findings were as follows: Hb 8 g/dl, RBC 238 x 10(4)/microliter, WBC
      2,900/microliter (band 1.0%, seg 18.5%, lym 28.0%, mono 44.0%, Baso 2.5%), Plt 13
      x 10(4)/microliter, PT 16.6"/10.9", APTT 44.7"/35.0". CSF contained 87 mg/dl of
      protein, 155 mg/dl of glucose and 2 mononuclear cells/microliter. Bone marrow was
      slightly hypercellular with mild increase in blast forms. No chromosome
      abnormality was found. CT and MRI revealed a large mass in the left fronto
      parietal region and the meninges showed marked thickening with enhancement after
      gadolinium-DTPA in MRI. The patient was treated with glycerol and steroid, but
      the subsequent course was complicated by a seizure, agitation, and pneumonia. He
      died from respiratory failure on January 13, 1996. The patient was discussed in a
      neurologic CPC and the chief discussant arrived at the conclusion that the
      patient had chronic myelomonocytic leukemia with infiltration of leukemic cells
      into meninges and the parenchyme of the cerebrum. Thickening of the dura was
      thought to be in part a reaction to the subdural hematoma as well as to leukemic
      cells along the meninges. Postmortem examination revealed hypercellular bone
      marrow with increase in monocytic cells (more than 20%). The lungs showed
      pneumonia with scattered old tuberculous lesions. The heart showed an old
      myocardial infarction in the posterior wall of the left ventricle. The brain
      showed an old chronic subdural hematoma in the left fronto-temporal region and a
      cystic mass lesion in the left frontoparietal region. The mass was hypercellular
      and most of them were monocytes. The dura mater showed reactive thickening
      without leukemic cell infiltration. It was concluded that this patient had
      chronic myelomonocytic leukemia with a formation of leukemic mass in the brain.
      Pathologists thought that the mass was a hematogenous spread. It is rare for
      chronic myelomonocytic leukemia to form a mass lesion in the brain.

PMID- 9621376
TI  - Regional difference in expression of characteristic abnormality of harlequin
      ichthyosis in affected fetuses.
AB  - Harlequin ichthyosis (HI) is a severe congenital ichthyosis in which newborn
      infants are covered with a thick plate of stratum corneum. We examined skin
      specimens from a variety of regions of the body including the scalp, face,
      tongue, trunk, upper and lower extremities, digits, palms, and soles of three
      fetuses affected with HI that were diagnosed prenatally. In all the skin regions,
      characteristic morphological abnormalities (absent or abnormal lamellar granules
      and intercellular lamellae, lipid inclusions in the cornified cells) were
      expressed in the late second trimester of the fetal period. The cornified cells
      in hair canals showed morphological abnormalities of HI more strongly than the
      interfollicular epidermis. Immunoblot study of epidermal extracts revealed that
      profilaggrin was much more prominent than filaggrin in all the hairy skin regions
      where the hair canals were extensively keratinized, but filaggrin was prominent
      in the palm. These observations support the idea that, in the hairy skin, HI
      phenotype expression is associated with keratinization and abnormal filaggrin
      metabolism in hair. In addition, the prenatal diagnosis or prenatal exclusion of
      HI is thought to be possible from whichever site of the fetal body the skin
      biopsy is taken in the late second trimester of the fetal period.

PMID- 9621377
TI  - Adoption and fostering of babies with Down syndrome: a cohort of 593 cases.
AB  - Recently, professionals in France have noticed an increase in newborns with Down
      syndrome (DS) being placed for adoption. The aim of this study was to investigate
      DS babies given up at birth for adoption and to consider the possible
      determinants of this in order to assess social acceptance of DS. A retrospective
      cohort of all living DS babies was collected from two birth-defect registries
      (Paris: 1981-1990; Marseilles area: 1984-1990). Follow-up data were collected:
      characteristics of the baby, biological parents and maternity units, age when
      given up for adoption, and type of foster care. The results showed that 19.4 per
      cent of infants with DS (115/593) were rejected by their parents. Multiple
      regression analysis indicated that foreign origin of the mother, area of
      residence, no associated major malformation, maternal age (15-24 years), and
      birth rank (> 2) variables were significantly associated with a lower placement
      rate. Among the 115 abandoned infants with DS, 88 came from unknown parentage
      (76.5 per cent). For half of them, adoptive placement (88/115) occurred before
      the age of 6 months. Socio-cultural attitudes play a great part in these family
      decisions. Equally important is the manner in which professionals propose
      adoption as an alternative to these parents of DS babies. They should be
      encouraged to consider all options before making a decision, so that the best
      solution can be found for the interest of all.

PMID- 9621378
TI  - Prenatal sonographic diagnosis of nasal malformations.
AB  - The aim of this study was to describe the prenatal detection of fetal nasal
      abnormalities by ultrasound. Transvaginal and transabdominal sonography was used
      for the detection of fetal malformations in 25, 114 cases. The fetal nose was
      visualized in all the fetuses in an oblique section and in the lateral profile of
      the face. Fifteen cases of fetal nasal malformations were detected between the
      12th and 27th week of gestation. All but two, who had dilatation and curettage,
      were confirmed by postabortal or postnatal examination. Dyskaryosis (trisomies 18
      and 21, triploidy, and tetrasomy 12 p) was diagnosed in six cases (40 per cent).
      The nasal malformations were isolated in four cases, one of them being associated
      with tetrasomy 12 p. The fetal nose should also be a target in the prenatal
      sonographic screening for malformations in the early mid-trimester. The incidence
      of fetal nasal anomalies is 1:1674 fetuses (15:25, 114). The fetal nose should be
      visualized by ultrasound in both an oblique plane and a lateral profile to
      identify its abnormalities.

PMID- 9621379
TI  - Charge flow separation: quantification of nucleated red blood cells in maternal
      blood during pregnancy.
AB  - We set out to ascertain the numbers of fetal cells that enter the maternal blood
      stream during pregnancy. Samples of 15-16 ml of whole blood were collected from
      225 women--mostly 10-18 weeks pregnant--and then processed by charge flow
      separation, a novel method based on free flow electrophoresis in a buffer
      counterflow gradient. After their recovery in four different separation
      instruments, nucleated red blood cells (NRBC) were enumerated histologically. In
      some cases fetal NRBC were identified and enumerated by fluorescence in situ
      hybridization with probes for the X and Y chromosomes and fetal haemoglobin mRNA.
      Recoveries were consistent among the four separation instruments: the median
      numbers of NRBC obtained were 4190, 1590, 2805 and 3860. Our data show that
      approximately 30 per cent of those cells were fetal. Thus, recent reports on the
      separation of fetal NRBC by other methods, give underestimates of their frequency
      in maternal blood.

PMID- 9621381
TI  - Holoprosencephaly.

PMID- 9621380
TI  - Amniocentesis before 14 completed weeks as an alternative to transabdominal
      chorionic villus sampling: a controlled trial with infant follow-up.
AB  - A (semi-) randomized controlled study with long-term follow-up was conducted to
      compare the effects of transabdominal chorionic villus sampling and early
      amniocentesis on fetal mortality and child morbidity. Women requesting early
      prenatal diagnosis for advanced maternal age were allocated to early
      amniocentesis or transabdominal chorionic villus sampling either by randomization
      or, if they declined randomization, by their own choice. Of the 212 women who
      entered the study, 117 were randomized, 70 chose early amniocentesis and 25 chose
      transabdominal chorionic villus sampling. Overall, 130 women underwent early
      amniocentesis and 74 underwent transabdominal chorionic villus sampling at a
      median gestation of 12 weeks. Two women were excluded because of fetal death
      before the procedure. Mosaic karyotypes were found in 5.4 per cent of the early
      amniocenteses and in none of the chorionic villus samples. All unintended fetal
      losses occurred after early amniocentesis with a frequency of 6.2 per cent (95
      per cent confidence interval: 2.7 per cent to 11.8 per cent). Talipes equinovarus
      was only observed after early amniocentesis with a frequency of 3.1 per cent (95
      per cent confidence interval: 0.8 per cent to 7.7 per cent). We conclude that
      chorionic villus sampling remains the method of choice if prenatal diagnosis is
      needed in the first trimester of pregnancy.

PMID- 9621382
TI  - Twin pregnancy discordant for trisomy 14 mosaicism: prenatal sonographic
      findings.
AB  - The survival of infants with trisomy 14 mosaicism has been scarcely reported in
      the literature, with only 15 cases being documented up to 1992. We present a case
      of a dichorionic twin pregnancy in which prenatal sonography at 24 weeks'
      gestation showed that one of the twins had several anomalies including
      intrauterine growth restriction, alobar holoprosencephaly, a cleft lip and
      palate, a recessive chin, a small stomach, overlapping fingers, a ventricular
      septal defect, and polyhydramnios. Twin 2 was structurally normal. In view of the
      lethal condition and associated polyhydramnios affecting one of the twins,
      prenatal surveillance for signs of tense polyhydramnios and premature labour was
      undertaken. The pregnancy proceeded uneventfully until 37 weeks, at which time a
      Caesarean section was performed. At birth, neonatal blood from the abnormal twin
      confirmed trisomy 14 mosaicism in 12 per cent of lymphocytes. The infant died on
      day 36 of life.

PMID- 9621383
TI  - Chorionicity inaccurately predicted by early ultrasound: a case report.
AB  - Ultrasound has been found to be extremely accurate in diagnosing the chorionicity
      of multiple gestations. Prenatal counselling and/or planning for selective
      termination is most often based on the sonographic prediction of chorionicity. We
      present a case of triplet pregnancy in which early sonographic prediction of
      chorionicity did not match the pathological diagnosis at delivery.

PMID- 9621384
TI  - Prenatal diagnosis of de novo interstitial 16q deletion in a fetus associated
      with sonographic findings of prominent coronal sutures, a prominent frontal bone,
      and shortening of the long bones.
AB  - De novo interstitial 16q deletion diagnosed in utero has not previously been
      reported. We present a case of fetal de novo interstitial 16q deletion associated
      with the sonographic findings of prominent coronal sutures, a prominent frontal
      bone, and shortening of the long bones. Genetic amniocentesis at 23 weeks'
      gestation revealed a de novo deletion of 16q13-q22. At birth, the fetus
      manifested a dysmorphic phenotype correlated with monosomy 16q syndrome. Linkage
      analysis of the family confirmed the maternal origin and the extent of the
      deletion. We suggest that prenatal detection of a prominent frontal bone with
      prominent cranial sutures and shortening of the long bones should prompt
      cytogenetic analysis looking for a deletion in the long arm of chromosome 16.

PMID- 9621385
TI  - Fetal bilateral subdural haemorrhages. Prenatal diagnosis and spontaneous
      resolution by time of delivery.
AB  - We report a patient diagnosed prenatally on routine fetal ultrasound, at 30
      weeks' gestation, with subdural haemorrhage. The mother had suffered a mild
      abdominal trauma and had Factor XI deficiency; however, both were felt to be
      aetiologically insignificant. Prenatal follow-up showed a complete resolution of
      the haematoma and no postnatal sequelae have been noted to date. The aetiologies
      and outcomes in the few previously reported cases are reviewed and compared with
      our case.

PMID- 9621386
TI  - First-trimester prenatal diagnosis of Ellis-van Creveld syndrome using linked
      microsatellite markers.
AB  - We report a personal experience of first-trimester prenatal diagnosis of Ellis
      van Creveld (EvC) syndrome based on typing of microsatellite markers flanking the
      EvC locus. An heterozygous fetus was diagnosed with a diagnostic accuracy of 96
      per cent. The DNA prediction was confirmed by ultrasound at 22 weeks of gestation
      and by clinical evaluation at birth.

PMID- 9621387
TI  - Increased nuchal translucency and CATCH 22.
AB  - Recent developments in cytogenetics has shown that 22q11 microdeletion is related
      to a broad spectrum of malformations which are described under the acronym CATCH
      22 (Cardiac, Abnormal faces, Thymic hypoplasia, Cleft palate, Hypocalcaemia and
      22 chromosome deletion). We describe a case of a fetus with increased nuchal
      translucency at 12 weeks' gestation presenting with congenital cardiac defects of
      DiGeorge syndrome type and hypocalcaemia at birth. The neonate was also diagnosed
      as carrying the 22q11 microdeletion. When nuchal translucency measurement is
      increased, CATCH 22 spectrum of malformations should be considered and therefore
      a thorough karyotype analysis should be performed to exclude microdeletion of
      chromosome 22.

PMID- 9621389
TI  - Correct estimation of parameters for ultrasound nuchal translucency screening.

PMID- 9621388
TI  - Response to: Wald, N.J., Hackshaw, A.K. (1997). Combining ultrasound and
      biochemistry in first-trimester screening for Down's syndrome, Prenat. Diagn.,
      17, 821-829.

PMID- 9621390
TI  - Current awareness in prenatal diagnosis.

PMID- 9621391
TI  - Effects of nicotine on the hypothalamic-pituitary-axis (HPA) and immune function:
      introduction to the Sixth Nicotine Round Table Satellite, American Society of
      Addiction Medicine Nicotine Dependence Meeting, November 15, 1997.
AB  - This meeting was the sixth consecutive Nicotine Round Table Satellite Meeting
      which was held in Washington, DC, on 15 November, 1996; previous meetings are
      presented in Table I. The overall objective of these meetings was to bring
      together scientists and clinicians as a means of developing a dialogue concerning
      the basic mechanisms of nicotine action and the effects of nicotine on the whole
      organism. The specific topic of this meeting was chosen because of the potent
      effects of nicotine on the hypothalamic-pituitary-axis (HPA), and newer concepts
      indicating that the immune system and the HPA are connected via a variety of
      neuroendocrine and neurotransmitter elements. Whereas the HPA appears to play a
      unique role in adapting to internal and external stressors, the immune system
      appears to act as a forward scout which provides information important to the
      HPA. This Satellite Meeting evaluated the effects of nicotine from three points
      of view: (1) the effects of nicotine on HPA function; (2) the effects of the HPA
      on the pharmacological effects of nicotine; and (3) the effects of nicotine on
      immune function. This specific presentation will provide an overview of the
      findings of the meeting and will discuss several of the overriding issues in this
      area of nicotine research.

PMID- 9621392
TI  - Response of the hypothalamo-pituitary-adrenal axis to nicotine.
AB  - Nicotine has been shown to be a potent stimulus for the secretion of the stress
      responsive hormones, adrenocorticotropin (ACTH) and prolactin. This paper reviews
      the findings by our laboratory and others that demonstrate the polysynaptic
      pathways involved in the neuroendocrine responses to systemic nicotine. It will
      focus primarily on the hypothalamo-pituitary-adrenal (HPA) axis and the effect of
      nicotine on ACTH secretion, with supplementary information on prolactin
      secretion, where relevant. Data are presented demonstrating that nicotine acts
      via a central mechanism to stimulate indirectly the release of ACTH from the
      anterior pituitary corticotropes. Nicotine does not appear to act directly at the
      hypothalamic paraventricular nucleus (PVN), the site of the corticotropin
      releasing hormone (CRH) neurons crucial to the regulation of ACTH. However,
      brainstem catecholaminergic regions projecting to the PVN showed a regionally
      selective and dose-dependent sensitivity to nicotine, particularly the
      noradrenergic/adrenergic nucleus tractus solitarius (NTS). A reduction in the
      modulatory effect of these catecholamines (by neurotoxic lesion, synthetic enzyme
      inhibitors or adrenergic receptor antagonists) resulted in an inhibition of
      nicotine-stimulated ACTH secretion. In addition, blockade of nicotinic
      cholinergic receptors (NAchRs) in the brainstem by the antagonist, mecamylamine,
      resulted in a dose-dependent reduction in norepinephrine (NE) release from
      terminals in the PVN, and a concomitant reduction in plasma ACTH. The
      differential sensitivity of these receptors to the nicotinic agonists, cytisine
      and nicotine, reflects the heterogeneity of the NAchR subtypes involved. The
      desensitization characteristics of the neuroendocrine responses to both acute and
      chronic nicotine exposure are indicative of an alteration in these NAchRs.

PMID- 9621393
TI  - Endogenous opioids and smoking: a review of progress and problems.
AB  - The present report examines efforts to elucidate the role of opioid mechanisms in
      the reinforcement of smoking. A number of approaches have been used to evaluate
      nicotine-opioid interactions. Opiate agonists such as heroin or methadone have
      been found to increase cigarette smoking reliably in humans, and morphine has
      been shown to increase the potency and efficacy of nicotine in rats. There is
      also an extensive literature documenting the nicotine-stimulated release of
      endogenous opioids in various brain regions involved in the mediation of opiate
      reinforcement. Blockade studies using opioid antagonists have not been as
      conclusive. Although animal models have demonstrated commonalities between
      nicotine withdrawal and the opiate abstinence syndrome, including reversibility
      by morphine, and although the impact of nicotine on certain response systems such
      as respiratory reflexes has clearly been shown to involve opioid mediation,
      attempts to demonstrate opioid modulation for the key indicators of smoking
      reinforcement--cigarette consumption and nicotine self-administration--have been
      fraught with difficulty. Resolution of the apparent contradictions will require
      taking into account: (a) the biphasic properties of nicotine-opioid effects at
      higher doses and anti-opioid effects at lower doses; (b) the contributions of the
      opioid receptor populations--mu, kappa, sigma--stimulated at various dose levels;
      (c) the possibility that endogenous-opioid activity is entrained primarily during
      the acquisition or re-acquisition of nicotine self-administration; (d) the
      possibility that the endogenous opioid response does contribute to nicotine
      reinforcement but only as a delimited component of the neuroregulatory cascade of
      nicotine; and (e) the possibility that opioids contribute primarily to nicotine
      reinforcement under special conditions such as stress. Taking these
      considerations into account should allow studies on endogenous opioid effects to
      begin to do justice to the complexity of both smoking behavior and the actions of
      nicotine.

PMID- 9621394
TI  - Endocrine effects of nicotine administration, tobacco and other drug withdrawal
      in humans.
AB  - The focus of this manuscript is on the effects of smoking and tobacco withdrawal
      on the hypothalamic-pituitary axis (HPA). A variety of studies have shown that
      nicotine administered intravenously or through intense cigarette smoking can
      induce changes in hormones associated with the HPA. Administration of, and abrupt
      cessation from, other drugs of abuse has also been shown to affect levels of
      these hormones. Additionally, many of the symptoms of stress and tobacco
      withdrawal overlap suggesting that the hormonal changes seen during periods of
      stress may be observed during tobacco abstinence. These findings led to a study
      of the effects of tobacco withdrawal on plasma ACTH, cortisol, and prolactin
      levels. The results indicated tobacco cessation caused small and transient
      effects on plasma hormone levels which were not significantly influenced by
      nicotine replacement and were not related to other signs of withdrawal.

PMID- 9621395
TI  - The role of corticosteroids in nicotine's physiological and behavioral effects.
AB  - This paper reviews evidence indicating that adrenal corticosteroids modulate the
      responsiveness of mice and rats to nicotine. Adrenalectomy increases, and both
      acute and chronic corticosteroid administration decrease, some of the
      physiological and behavioral effects of nicotine. One function of adrenal
      steroids may be to regulate stress-induced changes in nicotine sensitivity.
      Another is to mediate the development of chronic tolerance when nicotine is given
      intermittently, and when the resulting tolerance has a learned component. A role
      of glucocorticoids in the development of tolerance to nicotine is suggested by
      the findings that a conditioned elevation of plasma corticosterone, which
      anticipates nicotine delivery, accompanies the development of chronic tolerance
      and that environmental cues evoke a conditioned corticosterone response, but only
      after they have become associated with nicotine delivery. The mechanisms by which
      adrenal steroids modulate nicotine sensitivity are not known, although recent in
      vitro evidence suggests that steroids can rapidly and reversibly reduce nicotinic
      receptor function. While most of the data are consistent with the hypothesis that
      corticosteroids reduce nicotine responsiveness, and thus promote a learned form
      of tolerance, there are new findings that corticosteroids increase the
      development of sensitization to the locomotor-activating effects of nicotine.
      These data suggest that formulations postulating a unidirectional effect of
      corticosteroids on nicotine's actions (e.g. decreased sensitivity) must be
      revised to take into account interacting variables such as the specific nicotine
      effect being studied and whether that effect normally exhibits tolerance or
      sensitization. Finally, research is presented which indicates that the
      corticosterone-elevating effects of nicotine, previously reported for
      experimenter-administered drug, are also produced when nicotine administration is
      contingent on an operant response, and at a dose which sustains the development
      of nicotine self-administration in rats. These findings highlight the feasibility
      of using self-administration models in future explorations of the relationship
      between adrenal steroids and nicotine function.

PMID- 9621396
TI  - Nicotine and nicotinic receptors in the circadian system.
AB  - Considerable data support a role for cholinergic influences on the circadian
      system. The extent to which these influences are mediated by nicotinic
      acetylcholine receptors (nAChRs) has been controversial, as have the specific
      actions of nicotine and acetylcholine in the suprachiasmatic nucleus (SCN) of the
      hypothalamus. In this article we review the existing literature and present new
      data supporting an important role for nAChRs in both the developing and adult
      SCN. Specifically, we present data showing that nicotine is capable of causing
      phase shifts in the circadian rhythms of rats. Like light and carbachol, nicotine
      appears to cause phase delays in the early subjective night and phase advances in
      the late subjective night. In the isolated SCN slice, however, only phase
      advances are seen, and, surprisingly, nicotine appears to cause the inhibition
      rather than the excitation of neurons. Among nAChR subunit mRNAs, alpha 7 appears
      to be the most abundant subunit in the adult SCN, whereas in the perinatal
      period, the more typical nAChRs with higher affinity for nicotine predominate in
      the SCN. This developmental change in subunit expression may explain the dramatic
      sensitivity of the perinatal SCN to nicotine that we have previously observed.
      The effects of nicotine on the SCN may contribute to alterations caused by
      nicotine in other physiological systems. These effects might also contribute to
      the dependence properties of nicotine through influences on arousal.

PMID- 9621397
TI  - The effects of nicotine on the immune system.
AB  - Although considerable work has been done on the potential health effects of
      smoking, little is known about the contribution of nicotine to those effects.
      This paper presents an overview of the immune system, and a discussion of the
      existing literature on the effects of tobacco smoke and nicotine on immunity.
      Treatment with nicotine has been shown to influence all aspects of the immune
      system, including alterations in humoral and cellular immunity. In addition,
      preliminary data suggest that gender and genetic factors impact on the
      immunological effects of nicotine. Finally, the possible mechanisms that might
      mediate the effects of nicotine are discussed.

PMID- 9621398
TI  - Effect of nicotine on the immune system: possible regulation of immune responses
      by central and peripheral mechanisms.
AB  - Nicotine (NT) treatment impairs T-cell receptor (TCR)-mediated signaling, leading
      to the arrest of T cells in the G1 phase of the cell cycle and inhibition of the
      antibody plaque-forming cell (AFC) response to sheep red blood cells (SRBC). This
      paper summarizes some of the previous findings related to cigarette smoke/NT and
      the immune response, and presents preliminary evidence suggesting that mice
      chronically treated with NT (0.5 mg/day/kg body weight) have a depressed
      inflammatory response in the turpentine-induced abscess model of inflammation.
      This ability of nicotine to attenuate an inflammatory response may also be the
      cause of reduced mortality of chronically nicotine-treated mice from acute
      influenza A pneumonitis. Moreover, in LEW rats, decreased anti-SRBC AFC responses
      were also observed after intracerebroventricular (i.c.v.) administration of
      relatively small concentrations of NT (28 micrograms/day/kg body weight) which,
      when given peripherally, did not affect the AFC response. In vitro the addition
      of NT to T cells increased protein tyrosine kinase (PTK) activity and
      intracellular Ca2+ concentration [Ca2+]i. These results support the hypothesis
      that NT alters immune responses by directly interacting with T cells, as well as
      indirectly through brain-immune interactions.

PMID- 9621399
TI  - Cocaine-induced alterations in neuro-development.
AB  - Gestational exposure to licit drugs of abuse such as alcohol and cigarettes, and
      illicit drugs of abuse such as marijuana, cocaine, and opiates is the single
      largest, preventable cause of in utero developmental compromise of infants in the
      United States today. Clinical and preclinical data suggest that cocaine may act
      as a behavioral teratogen, a drug capable of altering fetal brain development and
      subsequent function. Although many children exposed to cocaine in utero have
      normal development, some subset of infants, especially those who have sustained
      more significant prenatal exposures, are at risk for developmental compromise.
      There does not appear to be one outcome, but a spectrum of outcomes, which may
      relate to individual genetic differences in mothers and infants, to the specifics
      of the pregnant woman's cocaine habit, as well as to the richness of the
      postnatal environment. Alterations of arousal and habituation are evident in some
      cocaine-exposed neonates, especially following greater in utero exposures. Subtle
      but profoundly important behavioral deficits may persist, as recent data suggests
      that some cocaine-exposed children may have particular difficulty modulating
      attention, impulsivity, and responsivity, which are critically challenged in
      classroom settings. The goals of this article are to present concepts required to
      better understand cocaine-induced alterations in neuro-development, to outline
      mechanisms that may underlie such changes, and to discuss the potential clinical
      consequences of such alterations.

PMID- 9621400
TI  - Prenatal cocaine exposure and child development: what do we know and what do we
      do?
AB  - The literature remains unclear about the effects of prenatal cocaine exposure on
      child development. Meanwhile, the implications for public policy and treatment
      and for our scientific understanding of the toxicity of cocaine are substantial.
      In this article we describe; (1) our current understanding of the effects of
      prenatal cocaine use and child outcome, (2) the issues that need to be
      investigated, and (3) implications for treatment of cocaine exposed children.
      Findings from our database of the published literature shows that our knowledge
      is still limited, scattered, and compromised by methodological problems that
      mitigate any conclusions about whether or not or how prenatal cocaine exposure
      affects child outcome. The cocaine problem is more complicated than first
      envisioned--it is a multifactorial problem including the use of other drugs,
      parenting, and environmental lifestyle issues. However, we also show that, even
      though the effects may be more subtle than initially anticipated, prenatal
      cocaine exposure will substantially increase in the number of school age children
      who will need special education services. Clinicians working with these children
      and families need to be prepared to address psychosocial and environmental
      issues, as well as developmental performance, in order to optimize their
      assessment and intervention.

PMID- 9621401
TI  - In utero cocaine exposure and language development.
AB  - A growing body of literature suggests that in utero cocaine exposure may place a
      child at risk for impaired language development. Because the field of gestational
      drug exposure and its effects on communicative development is young, the research
      is still limited and the data are contradictory, plagued by many methodological
      problems. The accumulating evidence, however, suggests that the development of
      specific aspects of language may be compromised in a percentage of children and
      that outcome is affected by a wide range of prenatal and postnatal biological and
      environmental factors. The data also suggest that deficits are best identified
      through the use of focused test batteries and may be evident only under stressful
      or difficult conditions. This article provides a critique and general overview of
      the literature on the early communicative and language development of prenatally
      cocaine-exposed children. Potential reasons for compromised language development
      and the clinical implications of these findings are discussed.

PMID- 9621402
TI  - Semantic development of African-American children prenatally exposed to cocaine.
AB  - Semantic content categories were described for the single word, multiple word,
      and verb relation utterances of 22 African-American 2-year-olds during a 90-min
      laboratory session. Half of the toddlers had been exposed prenatally to cocaine
      and half were unexposed, as documented by biological assay in the newborn period.
      The exposed and unexposed groups were carefully matched on demographic, medical,
      and proximal caregiving variables. Children's spontaneous utterances were
      transcribed from audio- and videotapes during the laboratory session and scored
      for semantic features by a team of reliable coders who were masked to child
      exposure status. General productive language features (utterance length,
      verbosity, and intelligibility) were also assessed. To evaluate general language
      and cognitive skills, the toddlers were evaluated with the Sequenced Inventory of
      Communicative Development-Revised (SICD-R) and the Bayley Scales of Infant
      Development (BSID). Although exposed and nonexposed toddlers exhibited similar
      sequences of semantic development, the exposed toddlers were more restricted and
      delayed in their semantic representations. No significant group differences were
      observed, however, for structural features of language (e.g., utterance length,
      distribution of utterance types) or for children's general language and cognitive
      functioning as assessed by standardized assessments (i.e., SICD-R, BSID). Thus, a
      history of prenatal cocaine exposure and associated risk factors (e.g., prenatal
      exposure to alcohol, diminished birth weight) are related to delays in early
      semantic development. Proposed diagnostic and treatment strategies are discussed.

PMID- 9621403
TI  - Play in children with prenatal cocaine exposure: development and implications for
      assessment.
AB  - Play assessment of children with prenatal cocaine exposure is discussed in terms
      of the developmental play level and behaviors manifest during spontaneous play
      and the clinical implications for assessing such children. Studies have found a
      number of subtle differences in the play skills of children with prenatal cocaine
      exposure compared to children with no cocaine exposure, however, sensitive
      outcome measures are needed to capture these subtle developmental differences.
      Suggestions for assessing play, an early developmental skill, using
      multidimensional play analyses that incorporate developmental play levels and
      associated play behaviors, such as initiation and perseveration are discussed.

PMID- 9621404
TI  - Current uses of gadolinium chelates for clinical magnetic resonance imaging
      examination of the liver.
AB  - The use of gadolinium chelates has become an integral part of magnetic resonance
      imaging (MRI) of the liver and extrahepatic abdomen. Although liver specific
      contrast agents are now available, gadolinium chelates continue to offer
      significant advantages for abdominal MRI. The gadolinium chelates uniquely
      provide important information about tumor perfusion that is key in our assessment
      of liver masses. These paramagnetic contrast agents assist with liver lesion
      detection, characterization, and in establishing the volume of viable perfused
      tumor. Gadolinium chelates are equally important for MRI of the extrahepatic
      abdomen. The interstitial accumulation of these agents within peritoneal,
      omental, and gastrointestinal tumor produces marked enhancement and is key in
      accurate tumor staging. Depiction of lesions within solid visceral organs such as
      the pancreas, kidneys, and spleen is also improved following gadolinium
      injection. The versatility of this workhorse contrast agent assures that
      gadolinium chelates will continue to occupy a central role in any busy abdominal
      MRI practice.

PMID- 9621405
TI  - Liver imaging with ferumoxides (Feridex): fundamentals, controversies, and
      practical aspects.
AB  - Superparamagnetic nanoparticles (Feridex) have been recently made available to
      the radiological community as a contrast agent for MR imaging of the liver. This
      article reviews the principal physicochemical characteristics of this new
      compound, with an emphasis on the explanation of the contrast obtained (either
      positive or negative enhancement) that depends on the local concentration and the
      sequence used. The clinical use of Feridex is detailed, both for lesion detection
      and characterization. Finally, some guidelines for image optimization are given.

PMID- 9621406
TI  - Enhanced magnetic resonance imaging for tissue characterization of liver
      abnormalities with hepatobiliary contrast agents: an overview of preclinical
      animal experiments.
AB  - Because of the demand for an extension of the range of diagnostic uses for
      currently available extracellular magnetic resonance imaging (MRI) contrast
      agents, a new generation of tissue-specific (i.e., hepatobiliary) contrast agents
      have been successfully developed to enhance the performance of hepatic MRI. These
      agents include mangafodipir trisodium (formerly manganese dipyridoxal diphosphate
      [Mn-DPDP]), gadoxetic acid (formerly gadolinium ethoxybenzyl
      diethylenetriaminopentaacetic acid [Gd-EOB-DTPA]), and gadolinium butylbenzyl
      diethylenetriaminepentaacetic acid (MS-264). In a series of experiments in
      animals, the potential of these agents for noninvasive characterization of liver
      lesions was evaluated with the use of a comprehensive methodology. The purpose of
      this report was to summarize the observed imaging behaviors of these agents
      toward different types of cholestasis and focal liver lesions, compare the
      similarities or dissimilarities of these agents in their possible mechanisms of
      action, and discuss the clinical implications of the results of the experiments.
      In summary, through intravenous administration of these agents, both global and
      local obstructive cholestases can be identified on the postcontrast image. With
      certain reliability, liver tumors of different origins and grades of cellular
      differentiation can be detected and classified according to their contrast
      enhancement patterns occurring at certain postcontrast phases. The invasiveness
      or degree of a malignancy of the liver tumor can also be suggested by the
      presence or absence of a peritumoral rim sign. Such diagnostic information,
      otherwise only invasively achievable, may prove to be invaluable in clinical
      decision making.

PMID- 9621407
TI  - Conformational stability and antibody response to the 18kDa heat-shock protein
      formulated into different vehicles.
AB  - Protein stability is one of the most important obstacles for successful
      formulation in the development of new-generation vaccines. Here, the 18kDa heat
      shock protein (18kDa-hsp) was chemically modified though conjugation with bovine
      serum albumin or by esterification with N-hydroxysuccinimide ester of palmitic
      acid. The biologically active conformation of the protein was preserved after
      chemical modification. The immune responses to the recombinant 18kDa-hsp from
      Mycobacterium leprae were studied in different presentations: free, copolymerized
      with bovine serum albumin in aggregates (18kDa-hsp-BSA), and either surface
      linked to liposomes or entrapped into liposomes. Measuring the antibody
      production of immunized genetically selected mice has compared the adjuvant
      effects of liposomes and proteic copolymer. Among the two liposome preparations,
      the strongest response was obtained with the surface-exposed antigen-liposomes.
      The copolymer 18kDa-hsp-BSA conferred a high titer of antibody in injected mice,
      and persisted 70 d after immunization. This approach should prove very useful for
      designing more effective vaccines by using 18kDa-hsp as carrier protein.

PMID- 9621408
TI  - Spectroscopic investigation on the interaction of NCA0424, a potent antitumor
      indoloquinoxaline derivative, with DNA.
AB  - NCA0424 (1), an indoloquinoxaline derivative, has a potent antitumor activity
      against in vitro and in vivo tumor models. To elucidate its structure-activity
      relationship, the interactions with various B-form DNAs were investigated by
      thermal denaturation, viscosity and circular dichroism (CD) measurements. The
      thermal stability of the DNA duplex was increased by the interaction with 1, and
      preferable binding for alternative purine-pyrimidine base sequence was suggested.
      Comparative viscometric measurements with ethidium bromide (an intercalator) and
      distamycin (a minor groove binder) suggested that 1 is an intercalator. The
      interaction of DNA with 1 revealed a new CD band at 340-390 nm. Taking advantage
      of this induced CD band, the equilibrium binding constants were determined for
      various DNAs, and the binding preference of 1 for the alternative purine
      pyrimidine base sequence, especially for the case of guanine as purine base, was
      indicated. The appearance of the induced CD band implies the importance of 1 side
      chain for the effective and/or stable intercalation of the aromatic ring into the
      DNA base pair.

PMID- 9621409
TI  - Further investigation of phenanthroindolizidine alkaloids from Tylophora tanakae.
AB  - In addition to ten alkaloids previously described, we have isolated two alkaloid
      N-oxides from Tylophora tanakae MAXIM. (Asclepiadaceae). Further, the polar
      fraction of the leaves and caules of this plant cultivated in a farm afforded two
      new polar alkaloids. The structures of the four products were determined. The
      relation between the structure and cytotoxic activity of this group of alkaloids
      is discussed.

PMID- 9621410
TI  - Synthesis and evaluation of water-soluble non-prodrug analogs of docetaxel
      bearing sec-aminoethyl group at the C-10 position.
AB  - To develop non-prodrugs of taxoids with satisfactory stability in vivo, high
      water-solubility, and potent antitumor activity, we prepared several 10-O-sec
      aminoethyl docetaxel analogs (3) and evaluated their cytotoxicity against mouse
      leukemia and human tumor cell lines, microtubule disassembly-inhibitory activity,
      and water-solubility. These analogs were synthesized from the 10-O-allyl baccatin
      derivatives (5a-c) using the beta-lactam synthon method. Among these analogs, the
      10-O-(2-morpholinoethyl) (18, 21) and 10-O-(2-thiomorpholinoethyl) (19, 24)
      analogs exhibited cytotoxicity comparable or superior to that of docetaxel (2).
      In addition, the methanesulfonic acid salt (18a) had a high water-solubility.

PMID- 9621411
TI  - Studies on nonpeptide angiotensin II receptor antagonists. III. Synthesis and
      biological evaluation of 5-alkylidene-3,5-dihydro-4H-imidazol-4-one derivatives.
AB  - 5-Alkylidene-3,5-dihydro-4H-imidazol-4-one derivatives were synthesized and
      evaluated for activity as angiotensin II receptor antagonists. Substitutions at C
      2 and C-5, respectively, with a propyl group and a 1-methylethylidene group
      resulted in the optimal compound, 3,5-dihydro-5-(1-methylethylidene)-2-propyl-3
      [[2'-(1H-tetrazol - 5-yl)biphenyl-4-yl]methyl]-4H-imidazol-4-one (2b), with a pA2
      value of 8.85 in rabbit aorta. When administered orally to rats, 2b showed a
      greater inhibitory effect on angiotensin II-induced pressor response than DuP
      753. Compound 2b also showed a good antihypertensive effect when administered
      orally to conscious sodium-depleted spontaneously hypertensive rats, with a
      duration of action of 24 h. These data suggest that 2b may be a useful agent for
      the treatment of angiotensin II-dependent diseases such as hypertension.

PMID- 9621412
TI  - 2-Oxopyrrolidines and 6-oxoperhydropyrrolo[1,2-a]pyrazines as templates in the
      search for nonpeptide cholecystokinin ligands.
AB  - In order to find new classes of non-peptide cholecystokinin (CCK) ligands, the
      conformational restriction of a series of weak 3-oxoindolizidine-based CCK
      antagonists has been both decreased and increased. This tactic yielded a series
      of monocyclic 2-oxopyrrolidine derivatives 4 with selectivity for CCK-A or CCK-B
      receptors and with slightly improved binding affinity at the CCK-A receptor
      subtype with respect to the model 3-oxoindolizidines. In contrast, the
      incorporation of the Trp residue at the secondary amino group of a pyrrolo[1,2
      a]pyrazine template 5, involving a drastic restriction in the conformational
      flexibility of the molecule, resulted in a series of bicyclic derivatives that
      did not bind to CCK receptors at concentrations up to 10(-5) M.

PMID- 9621413
TI  - 7-(2-Aminomethyl-1-azetidinyl)-4-oxoquinoline-3-carboxylic acids as potent
      antibacterial agents: design, synthesis, and antibacterial activity.
AB  - 2-Aminomethyl-1-azetidinyl, -1-pyrrolidinyl, and -1-piperidinyl groups were
      designed as novel C-7 substituents for potential antibacterial quinolone agents.
      Of the three substituents, the 2-aminomethyl-1-azetidinyl group (compound 12a)
      was found to be the most favorable for enhancing the activity of the 6,8
      difluoroquinoline molecule 12. Therefore the 2-aminomethyl-1-azetidinyl group was
      introduced into a variety of quinolines (giving 24-26a, and 28a) and
      naphthyridines (giving 31a and 32a). Through optical resolution of 1
      benzylazetidine-2-carboxamide (19) and chiral synthesis of its R-isomer, both
      enantiomers of 2-aminomethyl-1-azetidinyl quinolines 12a and 24-26a were also
      prepared. The most active of all the compounds was 5-amino-6,8-difluoroquinoline
      (R)-26a. The activity of (R)-26a was more potent than those of the corresponding
      1-piperazinyl derivative (3) and sparfloxacin (1), and was comparable to those of
      the corresponding 3-amino-1-pyrrolidinyl (4), 3-aminomethyl-1-pyrrolidinyl (5),
      and 3-amino-1-azetidinyl (6) derivatives.

PMID- 9621414
TI  - Synthetic studies on selectin ligands/inhibitors. Synthesis and biological
      evaluation of sulfated and phosphorylated beta-D-galacto- and lactopyranosides
      containing fatty-alkyl residues of different carbon chain lengths.
AB  - To investigate the biological selectin-ligand interactions, fourteen sulfated and
      eight phosphorylated beta-D-galacto- and lactopyranosides containing branched
      fatty-alkyl residues in place of the ceramide have been synthesized.
      Regioselective sulfation of the parent glycolipids through the dibutylstannylene
      acetal with a certain amount of sulfur trioxide-trimethylamine complex produced
      the target sulfated glycolipids, while stepwise phosphorylation by treatment of
      the properly protected diol with dibenzyloxy(diisopropylamino)phosphine gave the
      phosphorylated glycolipids. The synthetic glycolipids showed an interesting mode
      of inhibition of the binding of HL-60 cells to immobilized P-, L- and E-selectins
      during in vitro experiments. In addition, using computer modeling techniques, we
      examined the molecular basis for the ligand-selectin complex formation. These
      glycolipids may be useful as therapeutic agents against selectin-dependent
      inflammation.

PMID- 9621415
TI  - Stereochemistry and putative origins of flavanones found in post-administration
      urine of the traditional Chinese remedies shosaiko-to and daisaiko-to.
AB  - Optically active flavanones, dihydrowogonin and dihydrooroxylin A, were found in
      the urine of healthy volunteers who orally received the traditional Chinese
      remedies Shosaiko-to and Daisaiko-to on separate occasions. These remedies, which
      consisted of dried extracts of Scutellariae Radix and other herbs, contained the
      metabolic precursors of the flavanones, but not the flavanones themselves, in
      stoichiometrically sufficient amounts. Structures and stereochemistry of the
      flavanones were elucidated by UV, circular dichroism (CD), electron impact (EI)
      MS and 1H-NMR analyses, showing that the biotransformations from the
      corresponding flavones, wogonin and oroxylin A, were stereoselective with a
      preference for the S-enantiomers. The putative origins of the flavanones were
      confirmed in terms of pharmacokinetics. Renal excretion-time data of the
      flavanones and the flavones suggested that the stereoselective transformations
      might have occurred in the intestinal tract as a result of microfloral metabolism
      before absorption.

PMID- 9621416
TI  - Medicinal foodstuffs. XII. Saponin constituents with adjuvant activity from
      hyacinth bean, the seeds of Dolichos lablab L. (1): Structures of lablabosides A,
      B, and C.
AB  - From the glycoside mixture with adjuvant activity obtained from the hyacinth
      bean, the seeds of Dolichos lablab L., six new oleanane-type triterpene
      bisdesmosides, lablabosides A, B, C, D, E, and F, were isolated together with
      chikusetsusaponin IVa. The structures of lablabosides A, B, and C were determined
      on the basis of chemical and physicochemical evidence as follows: 3-O-[alpha-L
      rhamnopyranosyl (1-->2)-beta-D-galactopyranosyl (1-->2)-beta-D
      glucopyranosiduronic acid]-28-O-(beta-D-glucopyranosyl) oleanolic acid
      (lablaboside A), 3-O-[alpha-L-rhamnopyranosyl (1-->2)-beta-D-galactopyranosyl (1-
      >2)-beta-D-glucopyranosiduronic acid]-28-O-(beta-D-glucopyranosyl) 24-epi
      hederagenin (lablaboside B), 3-O-[alpha-L-rhamnopyranosyl (1-->2)-beta-D-
      galactopyranosyl (1-->2)-beta-D-glucopyranosiduronic acid]-28-O-[alpha-L
      rhamnopyranosyl (1-->2)-beta-D-glucopyranosyl] 24-epi-hederagenin (lablaboside
      C).

PMID- 9621417
TI  - Binding position of tolbutamide to human serum albumin.
AB  - The interaction between drugs (tolbutamide (1), 1-butyl-3-(methylsulfonyl)urea
      (2)) and human serum albumin (3) was investigated by equilibrium dialysis and NMR
      spectroscopy. The binding of 1 and 2 to 3 was concluded to be hydrophobic and
      hydrophilic, respectively, on the basis of the dependence of the binding
      constants on temperature, ionic strength, and chain length of fatty acid added.
      In 1H-NMR spectra of 1, there were no significant shifts with change in
      concentration or addition of 3. The spin-lattice relaxation time (T1) and spin
      spin relaxation rate (1/T2) of the respective protons of 1 were independent of
      concentration, but depended on the concentration of 3 added. The binding position
      was determined from the ratio of 1/T2 of 1 bound to 3 and free 1. 1 and 2 were
      found to bind to 3 through the tolyl group and sulfonylurea group, respectively.
      The binding property of 1 was considered to be governed by the competition
      between the hydrophobic effect of the tolyl group and the hydrophilic effect of
      the sulfonylurea group in the molecule.

PMID- 9621418
TI  - Enhancing effect of N-dodecyl-2-pyrrolidone on the percutaneous absorption of 5
      fluorouracil derivatives.
AB  - The enhancing effects of N-dodecyl-2-pyrrolidone (NDP) on the percutaneous
      absorption of doxifluridine (DOX), 5-fluorouracil (5-FU), tegafur (TEG) and
      carmofur (CAR) were examined using an in vitro penetration technique and rat
      skin. Phosphate buffered isotonic saline (PBS), propylene glycol (PG) and PG
      containing 0.4M NDP (PGNDP) were applied as the donor solution. The correlation
      between the n-octanol/water partition coefficients and the permeability
      coefficients of DOX, 5-FU and TEG was investigated using both logarithmic plots.
      It was determined that the permeability coefficients are significantly correlated
      with their n-octanol/water partition coefficients on PBS. This result suggested
      that the non-polar stratum corneum lipid lamella in the skin might act as a rate
      limiting step on the skin penetration of DOX, 5-FU and TEG. The permeability
      coefficient of DOX, 5-FU and TEG was increased on PGNDP. The enhancing effect of
      NDP on the permeability coefficient was more effective at higher hydrophilic
      drugs, the values of the permeability coefficient had almost the same values on
      PGNDP and the dependency of the permeability coefficient on the n-octanol/water
      partition coefficient disappeared in the presence of NDP. These results indicated
      that the enhancing effect of NDP on the percutaneous absorption of DOX, 5-FU and
      TEG might be closely related to the perturbation of stratum corneum lipid
      lamella. Since it has been well recognized that CAR is decomposed into 5-FU in
      neutral and alkaline solution, the decomposition rate of CAR was measured using
      PBS solution and was found to be very rapid (Kd = 3.17 h-1, t1/2 = 13.1 min). The
      total concentrations of CAR plus 5-FU in the acceptor compartment were used to
      determine the permeability coefficient of CAR. The obtained value of the
      permeability coefficient of CAR on PG was almost the same as that of TEG on PG
      (CAR: 1.11 x 10(-3) cm/h, TEG: 1.24 x 10(-3) cm/h), while that of CAR on PGNDP
      was smaller than that of TEG on PGNDP (CAR: 6.06 x 10(-3) cm/h, TEG: 1.24 x 10(
      2) cm/h). To determine the lipophilic property of CAR, the lipophilic index (log
      k') was measured by HPLC. The value of the lipophilic index of CAR was 92 times
      higher than that of TEG. These results indicated that CAR is a higher lipophilic
      compound, and the smaller value of the permeability coefficient of CAR compared
      with that of TEG on PGNDP might be caused by the strong binding of CAR to the rat
      skin (dermis). The dermis might act as a rate limiting step on the skin
      penetration of CAR, and the percutaneous absorption of CAR might be controlled by
      both the stratum corneum and the dermis.

PMID- 9621419
TI  - Enzymatic peptide synthesis with p-guanidinophenyl and p-(guanidinomethyl)phenyl
      esters as acyl donors.
AB  - Two series of "inverse substrates", N-Boc-amino acid p-guanidinophenyl and p
      (guanidinomethyl)phenyl esters, were prepared as acyl donor components for
      enzymatic peptide synthesis. The kinetic behavior of these esters toward bovine
      and Streptomyces griseus (SG) trypsin was analyzed. The spatial requirement of
      the active site of these enzymes for catalytic efficiency is discussed based on
      the steric characteristics of the substrates. These substrates were found to
      couple readily with amino acid p-nitroanilides to produce peptides. SG trypsin
      was the most efficient catalyst among the enzymes tested (bovine, porcine, and SG
      trypsin).

PMID- 9621420
TI  - Synthesis and antimicrobial activity of pyridines bearing thiazoline and
      thiazolidinone moieties.
AB  - Two series of new pyridines bearing thiazoline (3a--n) and thiazolidinone (5a--e)
      moieties were prepared via the cyclization of the corresponding substituted
      pyridyl thiourea (2a--g) with an appropriately substituted phenacyl bromide or
      chloroacetic acid, respectively. The antimicrobial activity was determined for
      representative compounds and most of them showed moderate activity against Gram
      positive bacteria.

PMID- 9621421
TI  - Synthesis of dipeptide-type human immunodeficiency virus (HIV) protease
      inhibitors with a binding unit to gp120.
AB  - Some dipeptide-type human immunodeficiency virus (HIV) protease inhibitors
      derived from KNI-102, with a N-carbomethoxycarbonylprolyl-phenylalanine benzyl
      ester (CPF) moiety as a binding site to gp120, were synthesized. Compounds 11a
      showed 7--100 times higher HIV protease-inhibitory activity (11a; IC50 = 0.90
      microgram/ml, 1.1 microM) than the standard compound 3 or 4 (3; IC50 = 3.7
      micrograms/ml, 7.7 microM, 4; IC50 = 75 micrograms/ml, 155 microM). Generally,
      the compounds substituted at the o-position of the phenoxyacetyl group 7a, 11a,
      16a and 21a showed several times higher inhibitory activity than 3.

PMID- 9621422
TI  - Antiproliferative constituents in umbelliferae plants. III. Constituents in the
      root and the ground part of Anthriscus sylvestris Hoffm.
AB  - The MeOH extract of the root and the ground part of Anthriscus sylvestris Hoffm.
      showed a high inhibitory activity against MK-1, HeLa, and B16F10 cell growth in
      vitro. The activity was found only in the CHCI3-soluble fractions. From the CHCI3
      soluble fraction of the root, falcarindiol, 1-(3'-methoxy-4',5'
      methylenedioxyphenyl)-1 xi-methoxy-2-propene, elemicin, and nemerosin were newly
      isolated in addition to deoxypodophyllotoxin (anthricin), anthriscusin, (-)
      deoxypodorhizone, and anthriscinol methyl ether which were reported earlier as
      constituents of the root of this plant. From the CHCI3-soluble fraction of the
      ground part, deoxypodophyllotoxin, (-)-deoxypodorhizone, nemerosin, and
      falcarindiol were isolated. In vitro antiproliferative activities of the isolates
      against MK-1, HeLa, and B16F10 cells are reported.

PMID- 9621423
TI  - Antiproliferative constituents in umbelliferae plants. IV. Constituents in the
      fruits of Anthriscus sylvestris Hoffm.
AB  - The constituents in the fruit of Anthriscus sylvestris Hoffm. were investigated,
      and four lignans [deoxypodophyllotoxin, morelensin, (-)-deoxypodorhizone, and (-)
      hinokinin], one phenylpropanoid [1-(3',4'-dimethoxyphenyl)-1 xi-hydroxy-2
      propene], two phenylpropanoid esters [3',4'-dimethoxycinnamyl (Z)-2
      angeloyloxymethyl-2-butenoate and 3',4'-dimethoxycinnamyl (Z)-2-tigloyloxymethyl
      2-butenoate], and one polyacetylenic compound (falcarindiol) were isolated. Their
      antiproliferative activity against MK-1, HeLa and B16F10 cell lines is reported.

PMID- 9621424
TI  - Effect of several hydrophilic polymers on the permeation of morphine and
      salicylic acid through excised hairless rat skin.
AB  - Several hydrophilic polymers changed the cumulative amount of morphine (MOR)
      permeated through excised hairless rat skin from 1% MOR hydrochloride solution
      containing ethanol and l-menthol at concentrations of 40% and 5%, respectively,
      as permeation enhancers. Anionic polymers (carboxyvinylpolymer and
      methylvinylether-maleic anhydride copolymer) in the test solutions decreased the
      skin permeation of MOR, whereas cationic polymers (polyethyleneimine and
      chitosan) increased it, compared with that without polymers. Little change,
      however, was observed by the addition of nonionic polymers
      (hydroxypropylcellulose and polyethyleneoxide). On the other hand, the cationic
      and anionic polymers in the test solutions decreased and increased, respectively,
      the skin permeation of salicylic acid (SA) from the same enhancing system
      containing sodium salicylate. These opposite results were probably caused by the
      change in escaping tendency of the drugs from the vehicles, which was due to the
      drug-polymer interaction. (The escaping tendency has a great effect on the drug
      partition from the polymer solution to the skin barrier). The effect of
      hydrophilic polymers on the partition was then evaluated by Donnan membrane
      theory. The partition of MOR was increased and decreased by the presence of
      polymers having identical and opposite charge to MOR. The low partition of the
      drugs to skin may also be caused by low diffusion of the drugs in the polymer
      solutions. The drug release from the hydrophilic polymer solutions was then
      measured, and the release rate was found to have decreased in the presence of
      polymers having opposite charge to MOR and SA. It is suggested that these drug
      polymer interactions changed the drug partition to skin thus changing the skin
      permeation of the drug.

PMID- 9621425
TI  - Novel indole S,O-bisdesmoside, calanthoside, the precursor glycoside of
      tryptanthrin, indirubin, and isatin, with increasing skin blood flow promoting
      effects, from two Calanthe species (Orchidaceae).
AB  - The methanolic extracts from Calanthe discolor LINDL. and C. liukiuensis SCHLTR.
      were found to exhibit hair restoring and skin blood flow promoting activities.
      Through bioassay-guided separation using the skin blood flow increasing effect, a
      novel indole S,O-bisdesmoside, calanthoside, was isolated together with three new
      components, glucoindican, calaliukiuenoside, and calaphenanthrenol, and known
      compounds such as tryptanthrin, indirubin, isatin, and indican. The structures of
      the new compounds were determined on the basis of physicochemical and chemical
      evidence and they showed an activating effect on skin blood flow. In addition, it
      was found that enzymatic hydrolysis of calanthoside with beta-glucosidase
      furnished tryptanthrin together with a small amount of indirubin and isatin,
      whereas indirubin and isatin were obtained from calanthoside by acid hydrolysis.
      Based on their contents in the fresh and dried plant, calanthoside may be a
      common genuine glycoside of tryptanthrin, indirubin, and isatin in the plant.

PMID- 9621426
TI  - Heart development in Drosophila and vertebrates: conservation of molecular
      mechanisms.
AB  - Vertebrate and insect (Drosophila) hearts look and function quite differently
      from each other. Nevertheless, during embryogenesis their mesodermal origin and
      initial assembly into a linear heart tube are comparable in many respects. In the
      past few years, numerous gene functions have been identified that are utilized by
      both vertebrates and Drosophila for the specification and differentiation of the
      heart progenitor cells. These studies have begun with the discovery of the
      homeobox gene tinman in Drosophila and its vertebrate counterparts. By now, there
      is also evidence that MEF2 transcription factors and TGF-beta signaling have
      cardiogenic functions in both these systems. Perhaps in a few years, the GATA and
      HAND transcription factors and Wnt signaling, which currently only have a
      demonstrated cardiogenic function in one of the systems, may also be part of this
      group. One of the pressing but still wide open questions is if the spectrum of
      targets for these transcription factors and signaling pathways is also conserved.

PMID- 9621427
TI  - Regulation and function of tinman during dorsal mesoderm induction and heart
      specification in Drosophila.
AB  - The homeobox gene tinman plays a key role in the specification of Drosophila
      heart progenitors and the visceral mesoderm of the midgut, both of which arise at
      defined positions within dorsal areas of the mesoderm. Here, we show that in
      addition to the heart and midgut visceral mesoderm, tinman is also required for
      the specification of all dorsal body wall muscles. Thus it appears that the
      precursors of the heart, visceral musculature, and dorsal somatic muscles are all
      specified within the same broad domain of dorsal mesodermal tinman expression.
      Locally restricted activities of tinman are also observed during its early,
      general mesodermal expression, where tinman is required for the activation of the
      homeobox gene buttonless in precursors of the "dorsal median" (DM) glial cells
      along the ventral midline. These observations, together with others showing only
      mild effects of ectopic tinman expression on heart development, indicate that
      tinman function is obligatory, but not sufficient to determine individual tissues
      within the mesoderm. Therefore, we propose that tinman has a role in integrating
      positional information that is provided by intersecting domains of additional
      regulators and signals, which may include Wingless, Sloppy Paired, and Hedgehog
      in the dorsal mesoderm and EGF-signaling at the ventral midline. Previous studies
      have shown that Dpp acts as an inductive signal from dorsal ectodermal cells to
      induce tinman expression in the dorsal mesoderm, which, in turn, is needed for
      heart and visceral mesoderm formation. In the present report, we show that
      Thickveins, a type I receptor of Dpp, is essential for the transmission of Dpp
      signals into the mesoderm. Constitutive activity of Tkv in the entire mesoderm
      induces ectopic tinman expression in the ventral mesoderm, and this results in
      the ectopic formation of heart precursors in a defined area of the ventrolateral
      mesoderm. We further show that Screw, a second BMP2/4-related gene product,
      Tolloid, a BMP1-related protein, and the zinc finger-containing protein Schnurri,
      are required to allow full levels of tinman induction during this process. It is
      likely that some of these functional and regulatory properties of tinman are
      shared by tinman-related genes from vertebrates that have similarly important
      roles in embryonic heart development.

PMID- 9621428
TI  - Dual role for the zeste-white3/shaggy-encoded kinase in mesoderm and heart
      development of Drosophila.
AB  - A Drosophila homolog of the serine/threonine kinase GSK-3 beta, encoded by the
      zest-white3/shaggy gene (zw3), has been implicated as a maternally provided
      antagonist of zygotic signaling by the secreted segmentation gene wingless (wg).
      The wg signal apparently causes a spatially localized inhibition of the
      ubiquitous repressor function of zw3. This double negative mechanism of signal
      transduction has been shown to mediate the patterning function of Wg in a number
      of developmental processes. Although wg is absolutely required for specifying the
      heart progenitors within the mesoderm of Drosophila, the role of zw3 in this
      process has been unclear. Here, we present evidence that zw3 has a dual role in
      mesoderm development: (1) zw3 acts as an antagonist in cardiogenic wg signal
      transduction, and (2) zw3 also seems to be required to promote positively the
      formation of a larger mesodermal region, the tinman- and dpp-dependent "dorsal
      mesoderm," which is a prerequisite not only for cardiogenesis, but also for
      visceral mesoderm formation. We also demonstrate that a recently identified
      proximal component of the wg cascade, which is a transcription factor encoded by
      pangolin/dTCF (dTCF), also seems to mediate wg-dependent cardiogenesis. Further,
      we present evidence that Notch (N), which opposes wg signaling in other
      situations, is unlikely to be directly involved in the cardiogenic wg pathway,
      but seems to have multiple other myogenic functions, one of which is to inhibit
      mesoderm differentiation altogether, when overexpressed as a constitutively
      active form.

PMID- 9621429
TI  - Dual functions of the heartless fibroblast growth factor receptor in development
      of the Drosophila embryonic mesoderm.
AB  - The Drosophila embryonic mesoderm forms by invagination of the ventral-most
      blastoderm cells. Subsequent development of this germ layer involves the
      dorsolateral migration of the internalized cells and expansion by cell division,
      followed by the specification of particular cell fates through the coordinate
      actions of both intrinsic and extrinsic regulatory mechanisms. The latter include
      several intercellular signals that function across germ layers. These processes
      combine to generate a diversity of mesodermal sub-types, including the cardial
      and pericardial cells of the heart or dorsal vessel, a complete set of somatic
      muscle founders each with its unique identity, a population of cells that form
      the visceral musculature, and other cells that develop into hemocytes and the fat
      body. Here, we review recent evidence for the involvement of a fibroblast growth
      factor receptor (FGFR) encoded by the heartless (htl) gene in early directional
      migration of the Drosophila mesoderm. In addition, we provide new data that 1)
      demonstrate a second role for Htl in promoting the specification of the
      precursors to certain cardiac and somatic muscle cells in the Drosophila embryo,
      independent of its cell migration function, 2) suggest that Ras and at least one
      other signal transduction pathway act downstream of Htl, and 3) establish a
      functional relationship between the Ras pathway and Tinman (Tin), a homeodomain
      factor that is essential for specifying some of the same dorsal mesodermal cells
      that are dependent on Htl. Finally, parallels between requirements for FGFR
      signaling in Drosophila and vertebrate mesoderm development are considered.

PMID- 9621430
TI  - tinman-related genes expressed during heart development in Xenopus.
AB  - The tinman homeobox gene of Drosophila is absolutely required for development of
      the insect heart. This observation prompted the isolation of tinman-related genes
      from vertebrates, in the hope that the developmental function of the gene would
      be conserved between evolutionarily distinct species. The first vertebrate tinman
      gene, Nkx2-5, was isolated from mouse and subsequently, orthologues of Nkx2-5
      have been isolated from a number of different species. In all cases, a conserved
      pattern of Nkx2-5 expression is observed in the developing heart, commencing
      prior to differentiation. Genetic ablation of Nkx2-5 in the mouse results in
      embryonic lethality due to heart defects, but most myocardial genes are expressed
      normally and a beating heart tube forms. This observation raises the possibility
      that additional genes related to Nkx2-5 are partially rescuing Nkx2-5 function in
      the null mouse. Recently, additional members of the tinman-related gene family
      have been discovered and characterized in a number of different species. Somewhat
      surprisingly, orthologous genes in different organisms can be rather divergent in
      sequence and may show completely different expression patterns. In at least some
      organisms, expression of the tinman-related genes is not observed in the heart.
      Due to the increasing number of family members and the somewhat divergent
      expression patterns, the precise role of the tinman-related genes in cardiac
      development remains an open question. In a search for additional tinman-related
      genes in the frog, Xenopus laevis, we have identified Nkx2-9, a novel member of
      the tinman-related gene family. Preliminary characterization reveals that Nkx2-9
      is expressed in the cardiogenic region of the embryo prior to differentiation,
      but transcript levels decrease rapidly, in the heart, at about the time that
      differentiation commences.

PMID- 9621431
TI  - Vertebrate homologs of tinman and bagpipe: roles of the homeobox genes in
      cardiovascular development.
AB  - In Drosophila, dorsal mesodermal specification is regulated by the homeobox genes
      tinman and bagpipe. Vertebrate homologs of tinman and bagpipe have been isolated
      in various species. Moreover, there are at least four different genes related to
      tinman in the vertebrate, which indicates that this gene has been duplicated
      during evolution. One of the murine homologs of tinman is the cardiac homeobox
      gene Csx or Nkx2.5. Gene targeting of Csx/Nkx2.5 showed that this gene is
      required for completion of the looping morphogenesis of the heart. However, it is
      not essential for the specification of the heart cell lineage. Early cardiac
      development might therefore be regulated by other genes, which may act either
      independently or in concert with Csx/Nkx2.5. Possible candidates might be other
      members of the NK2 class of homeobox proteins like Tix/Nkx2.6, Nkx2.3, nkx2.7, or
      cNkx2.8. Murine Tix/Nkx2.6 mRNA has been detected in the heart and pharyngeal
      endoderm (this study). Xenopus XNkx2.3 and chicken cNkx2.3 are expressed in the
      heart as well as in pharyngeal and gut endoderm. In contrast, murine Nkx2.3 is
      expressed in the gut and pharyngeal arches but not the heart. In zebrafish and
      chicken, two new NK-2 class homeoproteins, nkx2.7 and cNkx2.8, have been
      identified. Zebrafish nkx2.7 is expressed in both, the heart and pharyngeal
      endoderm. In the chicken, cNkx2.8 is expressed in the heart primordia and the
      primitive heart tube and becomes undetectable after looping. No murine homologs
      of nkx2.7 or cNkx2.8 have been found so far. The overlapping expression pattern
      of NK2 class homeobox genes in the heart and the pharynx may suggest a common
      origin of these two organs. In the Drosophila genome, the tinman gene is linked
      to another NK family gene named bagpipe. A murine homolog of bagpipe, Bax/Nkx3.1,
      is expressed in somites, blood vessels, and the male reproductive system during
      embryogenesis (this study), suggesting that this gene's function may be relevant
      for the development of these organs. A bagpipe homolog in Xenopus, Xbap, is
      expressed in the gut masculature and a region of the facial cartilage during
      development. In this paper, we discuss molecular mechanisms of cardiovascular
      development with particular emphasis on roles of transcription factors.

PMID- 9621432
TI  - Combinatorial interactions regulating cardiac transcription.
AB  - In vertebrates, heart development is a multistep process that starts with
      formation and patterning of the primitive heart tube and is followed by complex
      morphological events to give rise to the mature four-chambered heart. These
      various stages are characterized by distinct patterns of gene expression.
      Although chamber specificity and developmental regulation can be demonstrated in
      transgenic mice using short promoter fragments, the mechanism underlying spatial
      and temporal specificity within the heart remains largely unclear. Combinatorial
      interaction between a limited number of cardiac-specific and ubiquitous
      transcription factors may account for the diverse genetic inputs required to
      generate the complex transcriptional patterns that characterize the developing
      myocardium. We have used the cardiac atrial natriuretic peptide (ANP) promoter to
      test this hypothesis. The ANP gene is transcribed in a spatial- and temporal
      specific manner in the heart, and a 500 bp promoter fragment is sufficient to
      recapitulate both chamber and developmental specificity. This promoter is
      composed of three modules, a "basal" cardiac promoter that is essential for
      transcription in embryonic and postnatal atrial and ventricular myocytes and two
      other independent modules that behave as chamber-specific enhancers. The basal
      cardiac promoter is the target of two cardiac-specific transcription factors, the
      zinc finger GATA-4 protein and the Nkx2-5 homeodomain, which bind to contiguous
      elements within this region. At low concentrations--a situation that likely
      occurs during the very first stages of cardiac cell fate determination--the two
      proteins synergistically activate transcription from the ANP promoter. This
      functional synergy requires physical interaction between the GATA-4 protein and
      an extended C-terminal homeodomain on Nkx2-5. This interaction, which unmasks an
      activation domain present just N-terminal of the homeodomain, is specific for
      GATA-4 and-5, but is not observed with the other cardiac GATA factor, GATA-6.
      Optimal synergy requires binding of both proteins to their cognate sites,
      although modest synergy also could be observed on heterologous promoters
      containing only multimerized Nkx binding sites, suggesting that Nkx2-5 is able to
      recruit GATA-4 into a transcriptionally active complex. The GATA/Nkx interaction,
      which appears to have been evolutionary conserved in nematode, fly, and mammals,
      provides a paradigm for analyzing transcription factor interaction during
      organogenesis. The data are also discussed in the context of our present
      knowledge of the roles of GATA and NK2 proteins in cardiac development.

PMID- 9621433
TI  - Common role for each of the cGATA-4/5/6 genes in the regulation of cardiac
      morphogenesis.
AB  - The GATA-4/5/6 genes encode transcription factors implicated previously in the
      regulation of cardiac-specific differentiation programs. However, recent analyses
      of mouse GATA-4 null mutations found evidence for function in endoderm
      development (in vitro) and embryonic morphogenesis (in vivo). Whether each of the
      three cardiac-associated GATA factors function within distinct or common
      developmental programs was previously untested; past studies defined specific and
      distinct roles for each of the GATA-1/2/3 genes in embryonic hematopoiesis. In
      this study, we compare the transcript patterns of cGATA-4/5/6 during chick
      embryogenesis. Each of the three GATA factors is expressed in a similar pattern
      within gastrulating cells of the primitive streak, prior to determination of the
      cardiomyocyte progenitors, and later within the lateral plate mesoderm and
      associated endoderm layer. The patterns overlap but extend beyond the presumptive
      cardiomyocyte population expressing cNkx-2.5. Later in development, cGATA-4/5/6
      are all transcribed throughout the differentiating heart, in similar but not
      identical patterns, within the endocardium, myocardium, and great vessels. In
      order to test the function of GATA factors during chick cardiogenesis, embryos
      were cultured in vitro in the presence of antisense oligomers designed to deplete
      specifically transcripts encoding cGATA-4/5/6, beginning around stage 7. When
      oligomers are used to target transcripts for all three genes, a high percentage
      of the embryos develop abnormal hearts related to the failure to form a normal
      primitive heart tube. In the most severe phenotype, cardiac bifida results in two
      bilateral beating hearts. In some embryos, the paired heart primordia undergo
      partial fusion but fail to form a single looping heart tube. In all cases,
      cellular differentiation is not obviously affected, as the abnormal hearts form
      beating tissue. Depletion of transcripts encoding any single GATA factor, or any
      combination of two GATA factors, does not affect development. The partial
      depletion of all three genes in chick results in a remarkably similar phenotype
      compared to the null GATA-4 mutation in mouse. Therefore, in the chick, each of
      the GATA-4/5/6 genes functions in a common pathway, at the time of cardiac
      crescent formation, for regulating early embryonic cardiac morphogenesis,
      apparently associated with embryonic folding or the migration of primordia to
      form a primitive tube.

PMID- 9621434
TI  - Patterning the heart's left-right axis: from zebrafish to man.
AB  - Normal left-right asymmetry is highly conserved among vertebrates. Errors in the
      proper patterning of this axis are believed to lead to congenital anomalies of
      the heart and abdominal viscera, often with profound clinical consequences. We
      review briefly the nature of potential signals and signaling sources that lead to
      the break in left-right symmetry. The evidence suggests that left-right reversal,
      or homogenization, of these signals may lead to different consequences, and we
      explain some malpositions and malalignments of the atria, ventricles, and/or
      outflow tract that are seen in a variety of congenital cardiac diseases. We
      speculate that there are units of organ assembly responsive to laterality
      signals, and these units may be driven independently. One crucial source of
      signals appears to be the notochord and floorplate. In order to examine the
      clinical relationship of these midline structures to putative disorders of
      laterality, we review all patients with disturbances of normal laterality seen at
      the Massachusetts General Hospital over the past 20 years. We find a significant
      association between laterality defects and anomalies of the spine and other
      midline structures.

PMID- 9621435
TI  - Screening mosaic F1 females for mutations affecting zebrafish heart induction and
      patterning.
AB  - The genetic pathways underlying the induction and anterior-posterior patterning
      of the heart are poorly understood. The recent emergence of the zebrafish model
      system now allows a classical genetic approach to such challenging problems in
      vertebrate development. Two large-scale screens for mutations affecting zebrafish
      embryonic development have recently been completed; among the hundreds of
      mutations identified were several that affect specific aspects of cardiac
      morphogenesis, differentiation, and function. However, very few mutations
      affecting induction and/or anterior-posterior patterning of the heart were
      identified. We hypothesize that a directed approach utilizing molecular markers
      to examine these particular steps of heart development will uncover additional
      such mutations. To test this hypothesis, we are conducting two parallel screens
      for mutations that affect either the induction or the anterior-posterior
      patterning of the zebrafish heart. As an indicator of cardiac induction, we
      examine expression of nkx2.5, the earliest known marker of precardiac mesoderm;
      to assess anterior-posterior patterning, we distinguish ventricle from atrium
      with antibodies that recognize different myosin heavy chain isoforms. In order to
      expedite the examination of a large number of mutations, we are screening the
      haploid progeny of mosaic F1 females. In these ongoing screens, we have
      identified four mutations that affect nkx2.5 expression as well as 21 that
      disrupt either ventricular or atrial development and thus far have recovered
      several of these mutations, demonstrating the value of our approach. Future
      analysis of these and other cardiac mutations will provide further insight into
      the processes of induction and anterior-posterior patterning of the heart.

PMID- 9621436
TI  - Comparison of blood viscosity in red-eared sliders (Trachemys scripta) adapted to
      cold and room temperature.
AB  - Red-eared sliders (Trachemys scripta) in their northern range undergo hibernation
      at temperatures of about 5 degrees C, which may result in a profound bradycardia
      and a drop in blood pressure leading to very slow blood flows. Blood viscosity
      increases with decreasing temperature and at low shear rates associated with slow
      blood flows. To investigate the effects of temperature on the blood viscosity of
      these animals, 20 red-eared sliders were randomly assigned to each of two groups,
      cold environment (5 degrees C) or room-temperature environment (25 degrees C). At
      the end of 5 months treatment, hematocrit values, plasma protein concentration,
      and whole-blood viscosity values were determined for each turtle. Blood viscosity
      measurements were determined at five shear rates (3.75, 15, 30, 75, and 150 s-1)
      at 5 degrees C and 25 degrees C for all animals. No significant differences were
      found in hematocrit or plasma protein values between cold-adapted and room
      temperature-adapted animals. Whole-blood viscosity between groups at any shear
      rate at a temperature of 5 degrees C was also nonsignificant. The only
      significant difference in blood viscosity between turtles adapted to cold and
      room temperature occurred at a shear rate of 3.75 s-1 at 25 degrees C. The whole
      blood viscosity of red-eared sliders, whether adapted to cold or to room
      temperature, tended to be lower as compared to other vertebrates under similar
      conditions of temperature, shear rate, and hematocrit. This innate lower blood
      viscosity may compensate for the potential detrimental effects on blood viscosity
      brought about by the low temperatures and decreased shear rates that occur in
      these animals during hibernation.

PMID- 9621437
TI  - Thermal response of Heterorhabditis bacteriophora transformed with the
      Caenorhabditis elegans hsp70 encoding gene.
AB  - A heat-shock response is induced when cells are exposed to temperatures slightly
      higher than their optimal physiological temperature. This response is based on
      the synthesis of heat-shock proteins encoded by the heat-shock genes. A
      correlation between the increased thermotolerance and production of 70-kDa heat
      shock protein (hsp70) has been observed in many organisms. We tested this
      hypothesis by transferring a Caenorhabditis elegans heat-inducible hsp70 A
      encoding gene into the entomopathogenic nematodes Heterorhabditis bacteriophora
      Hp88. Successful transformation of the gene was confirmed by Southern blot
      hybridization and polymerase chain reaction. Our blot studies showed that the
      transgenic nematodes contained five to ten copies per genome of the introduced
      hsp70 A gene. hsp70 mRNA transcripts were detected in both wild-type and
      transgenic nematodes. Transcripts increased severalfold in transgenic nematodes
      upon heat shock. Infective juveniles of both transgenic and wild-type nematodes
      that exposed to a sublethal heat treatment (35 degrees C) for 2 h followed by a
      normally lethal heat treatment (40 degrees C) for 1 h. More than 90% of
      transgenic nematodes survived heat treatment, compared to 2% to 3% of the wild
      type strain. Our observations establish that overexpression of hsp70 A gene
      resulted an enhanced thermotolerance in the transgenic nematodes. The transgenic
      nematodes displayed normal growth and development.

PMID- 9621438
TI  - Embryogenesis-promoting factors in rat serum.
AB  - Regarding whole rat embryo cultures in vitro, rat serum as a culture medium is
      known to support the normal growth of rat embryos in the organogenesis phase. The
      purpose of the present study was to isolate the embryogenesis-promoting factors
      from rat serum as a first step in the development of a defined serum-free medium
      for a whole embryo culture system. Pooled rat serum after heat inactivation was
      fractionated into three major peaks (frA, containing a region of void volume,
      frB, and frC) by gel filtration. The 9.5-day rat embryos that were cultivated for
      48 hr in essential salt medium containing frB (with a molecular size range of 100
      500 kDa) revealed normal growth. Three proteins (27 kDa, 76 kDa, and 190 kDa)
      that had the embryogenesis-promoting effects were isolated from 3-hr delayed
      centrifuged rat serum by the ion exchange chromatography. The 76-kDa protein was
      found to be rat transferrin by immunoblotting. The 27-kDa protein was identified
      as apo-AI (the major apoprotein of high-density lipoprotein) by immunoblotting.
      High-density lipoprotein obtained from pooled rat serum by a NaBr density
      gradient ultracentrifugation was found to have a positive effect on
      embryogenesis. The 10-kDa protein was also identified as alpha 1-inhibitor 3 by
      immunoblotting. In addition, the embryogenesis-promoting effect of the fraction
      containing 27-kDa and 190-kDa proteins declined within a short period of storage
      at -20 degrees C. This decrease was countered by supplementing its fraction (D-2)
      with albumin isolated from rat serum. These results in the present study suggest
      that transferrin, high-density lipoprotein, and alpha 1-inhibitor 3 in rat serum
      may be embryogenesis-promoting factors, and that albumin appeared to play a role
      in the embryogenesis of rat embryos in whole embryo cultures.

PMID- 9621439
TI  - Changes in circulating insulin and corticosterone concentrations during different
      reproductive phases and their relationships to body weight and androstenedione
      concentration of male Scotophilus heathi.
AB  - The aim of the present study was to determine the serum levels of insulin and
      corticosterone during different reproductive stages in a natural population of
      the male bat, Scotophilus heathi and their relationship to body weight and
      androstenedione level. Changes in body weight were marked by weight gain before
      winter dormancy and weight loss during winter dormancy. Circulating insulin level
      varied significantly over the season and correlated positively with changes in
      body weight and androstenedione level. Circulating corticosterone level also
      varied significantly over the season but correlated negatively with changes in
      body weight and androstenedione level. High corticosterone level during August
      coincided with a period of increased feeding activity in this species. The
      results suggest that insulin may act as an anabolic agent to promote fat
      deposition and corticosterone exerts a predominantly fat-mobilizing influence. A
      high insulin level prior to winter dormancy may be an important factor
      responsible for inducing high androstenedione concentration shown in Scotophilus
      heathi.

PMID- 9621440
TI  - Yolk protein synthesis in the riceland tadpole shrimp, Triops longicaudatus,
      measured by in vitro incorporation of 3H-leucine.
AB  - Investigation of reproductive control within the tadpole shrimp, Triops
      longicaudatus, required the isolation and characterization of the yolk protein
      (vitellin, Vn). To this end, tadpole shrimp were cultured in environmental
      chambers (29 degrees C-22 degrees C, with 14:10 light:dark cycle). Desiccated
      cysts hatched in 2-3 days after inundation. The tadpole shrimp began egg
      deposition 7 to 8 days after hatching and exhibited a mean growth rate of 1.85 +/
      0.24 mm/day. It was observed that 4-day-old shrimp had visible eggs in their
      ovaries. In addition, Vn was isolated and characterized from reproductive
      animals, resolving as one protein on native PAGE, and possessing a molecular
      weight (MW) of 376,000 +/- 2,900 as determined by FPLC. Examination by SDS-PAGE
      revealed that Vn is composed of a single molecule with a MW of 214,000 +/- 2,000.
      Methyl farnesoate (MF), a crustacean compound whose role in reproduction is still
      being elucidated and is structurally similar to juvenile hormone III (JH III) was
      incubated with ovarian explants. These explants were incubated for 24 h at room
      temperature in EAGLE's medium adjusted to Van Harreveld's solution in six
      concentrations (1 pM to 100 nM) of MF and JH III. Methyl farnesoate and JH III
      had no direct in vitro effect on yolk protein synthesis (P < or = 0.545 and P <
      or = 0.815, respectively).

PMID- 9621441
TI  - Characterization of deposits in human lung tissue by a combination of different
      methods of analytical electron microscopy.
AB  - Energy-filtering transmission electron microscopy (EFTEM) was used for imaging of
      deposits in anthracotic areas of human lung tissue. Unstained ultrathin sections
      were investigated with a Philips CM20 operated at 200 kV acceleration voltage and
      equipped with a GATAN imaging filter and an X-ray detector for correlative
      analysis. The distribution of soot particles in the anthracotic areas could be
      visualized by recording C-K elemental maps, and inorganic particles between the
      soot by recording C-K jump ratio images. They could be identified as the mineral
      muscovite and as an iron oxide phase, which would have been overlooked and
      obviously their composition would not have been recognized using conventional TEM
      investigations with stained ultrathin sections. Oxide phases of the inorganic
      particulates were imaged by recording O-K elemental maps, and silicate and Fe
      phases with Si-L23 and Fe-L23 jump ratio images, respectively. The interpretation
      of the elemental maps was supported by recording EEL and EDX spectra from
      interesting specimen regions. Electron diffraction patterns were used to
      characterize the mineral crystals.

PMID- 9621442
TI  - Rapid analysis of steroidal saponin mixture using electrospray ionization mass
      spectrometry combined with sequential tandem mass spectrometry.
AB  - Using electrospray ionization mass spectrometry (MS) combined with sequential
      tandem MS(ESI-MSn), two major steroidal saponins extracted from Tribulus
      terrestris were studied, and considerable useful structural information was
      obtained. The structure of the proposed known steroidal saponin was verified, and
      the structure of the unknown saponin was investigated using MSn experiments. Some
      special fragment ions were also observed, and the corresponding fragmentation
      mechanisms were investigated which are characteristic for steroidal saponins and
      can give some information on the linkage position of some sugar groups in
      saponins. This methodology has been established as a powerful tool for the rapid,
      comparative analysis of mixtures such as crude plant extracts.

PMID- 9621443
TI  - A novel derivatization method with 5-bromonicotinic acid N-hydroxysuccinimide for
      determination of the amino acid sequences of peptides.
AB  - We have developed a novel method that effectively identifies the N-terminal
      product ions produced in the tandem mass spectrometry (MS/MS) analysis of
      peptides done in conjunction with the specific derivatization of the N-terminal
      amino group using 5-bromonicotinic acid N-hydroxysuccinimide ester (BrNA-NHS).
      Electrospray ionization with low-energy collision-induced dissociation (CID)
      MS/MS clearly differentiated the N-terminal product ions labeled with the 5
      bromonicotinyl group from other ions, on the basis of the appearance of CID peaks
      with a doublet pattern characteristically separated by 2 mass units produced by
      the equal natural abundances of 79Br and 81Br. The tracing of a series of these
      bromine-containing product ions allows the easy amino acid sequencing of
      peptides. Using Gln-Arg-Leu-Gln-Ser-Asn-Gln-Leu-Lys as the test peptide, we found
      that within 30 minutes at pH 6.5 and 37 degrees C its alpha-amino group was
      completely acylated with BrNA-NHS (peptide: BrNA-NHS = 1:40; mol/mol). The
      epsilon-amino group of the C-terminal lysine residue was less likely to be
      acylated under these conditions, being only partly modified (about 20%). This
      suggests the possibility of keeping the epsilon-amino group free from acylation.
      The method was successfully applied to the determination of the amino acid
      sequences of peptides from porcine kidney aminoacylase I produced by digestion
      with lysyl endopeptidase and with Staphylococus aureus V8 protease.

PMID- 9621444
TI  - Cellular uptake profile of paclitaxel using liquid chromatography tandem mass
      spectrometry.
AB  - A new method for studying cellular uptake has been developed. This method is
      based on selected reaction monitoring liquid chromatography tandem mass
      spectrometry analysis of preparations from cell culture. The limit of detection
      for paclitaxel was approximately 0.1 microM intracellular concentration. This
      method has been utilized to study the uptake of paclitaxel and an analog (BMS
      190616) in normal and multidrug resistant (MDR) cell lines. Paclitaxel and the
      analog, that had been noted to overcome MDR in animal models, were incubated with
      normal cells (HCT116) and MDR cells (HCT116(VM)46) at therapeutic concentrations.
      Intracellular drug concentrations were assayed at intervals from 0 to 1.0 h.
      Results show that paclitaxel accumulates to a level 12 times greater and BMS
      190616 to a level 5 times greater in the normal cells as compared to MDR cells
      suggesting that paclitaxel is more sensitive to MDR than the analog. Furthermore,
      the steady state level of BMS-190616 was 4 fold greater than paclitaxel in the
      MDR cell line suggesting that at least part of this compound's increased
      therapeutic effect can be attributed to processes of uptake and efflux at the
      cellular level. These data show that the method is rapid, sensitive and presents
      a unique advantage over traditional radioisotopic methods in that it can readily
      be employed on a range of analogs without any additional synthetic effort.

PMID- 9621445
TI  - Detection of the bacteriological sex factor in E. coli by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry.
AB  - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry is
      employed to detect the presence of the bacteriological sex factor, a trait that
      allows some bacteria to transfer genetic information to others by means of
      conjugation. The principal advantage of the method is its speed. Twenty different
      strains of E. coli were analyzed and the results were consistent with previously
      known genetic information. The sex factor could be transferred from one strain to
      another and the outcome verified by mass spectrometry.

PMID- 9621446
TI  - Fingerprint matching of E. coli strains with matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry of whole cells using a
      modified correlation approach.
AB  - We have developed a mathematical algorithm to compare and distinguish matrix
      assisted laser desorption/ionization (MALDI) mass spectra of whole bacteria
      cells. This fingerprint matching technique eliminates the subjectivity involved
      in visually comparing two spectra to determine whether they match and it provides
      a quantitative measure of spectral similarity. Using it, we have distinguished
      twenty five different strains of a single bacteria species, E. coli. Cells are
      grown in culture, samples are prepared, and MALDI-TOF mass spectra are recorded
      for each strain. Pairs of spectra are compared by a modified cross-correlation
      procedure. This modified approach increases the sensitivity of correlation
      analysis to small spectral differences. The technique can be fine-tuned by
      varying the number of intervals into which spectra are divided.

PMID- 9621447
TI  - Electrospray ionization and collision-induced dissociation time-of-flight mass
      spectrometry of neutral glycosphingolipids.
AB  - A series of native naturally occurring neutral glycosphingolipids has been
      analysed by electrospray ionization tandem mass spectrometry using a hybrid
      magnetic sector-TOF instrument. The collision-induced dissociation products of
      precursor ions were detected by an orthogonal acceleration time-of-flight mass
      spectrometer as the second analyser. Glycosphingolipids, with mono- to hexa
      saccharide chain lengths with different ceramide constituents, were studied. The
      result of electrospray ionization in the positive ion mode generally showed
      singly charged molecular ions with Na+ as adduct, [M + Na]+. The sensitivity of
      the electrospray ionization was greatly enhanced by addition of NaCl, LiCl
      (forming [M + Li]+) or KCl (yielding [M + K]+) to the sample. A comparison
      between the collision-induced dissociation of precursor molecular ions of
      monoglycosylceramides, using Na+, Li+ and K+ as adducting species, showed that
      the intensity of the fragment ions and the extent of the daughter ion
      fragmentation of the molecular ions, are dependent on the type of adduct used.
      The daughter ion spectra of Li+ adduct ions showed intense sequence fragment
      ions, both of the saccharide chain and the ceramide moiety, and were superior to
      those obtained using Na+ or K+. The collision-induced dissociation spectra of the
      [M + Li]+ ions, of glycosphingolipids containing di- to hexasaccharides, are also
      presented. Proposed possible fragments, resulting from the CID of the molecular
      ions [M + Li]+ of monoglycosylceramides, are shown.

PMID- 9621448
TI  - Biochemical characterization of a haloalcohol dehalogenase from Arthrobacter
      erithii H10a.
AB  - Arthrobacter erithii H10a possesses two enzymes capable of catalyzing the
      dehalogenation of vicinal halohydrins which have been designated as dehalogenases
      DehA and DehC. The DehA dehalogenase demonstrated greater activity toward 1,3
      dichloro-2-propanol (1,3-DCP) while the DehC dehalogenase showed higher activity
      toward 3-chloro-1,2-propanediol (3-CPD) and brominated alcohols. The DehA
      dehalogenase was composed of two non-identical subunits (relative molecular mass
      of 31.5 and 34 kDa) which probably associate with other proteins to form a large
      catalytically active protein of 200 kDa. The two subunits were purified and the
      amino acid sequence of their tryptic digests determined. The DehA enzyme
      catalyzed the conversion of vicinal halohydrins to epoxides and the reverse
      reaction in the presence of an excess of halogen. This enzyme had maximum
      activity at 50 degrees C and a broad pH optimum over the range 8.5-10.5. The
      apparent K(m) and Vmax values for dehalogenation of 1,3-DCP and 3-CPD were 0.105
      mM and 223 mumol min-1 mg-1; and 2.366 mM and 1.742 mumol min-1 mg-1,
      respectively. The enzyme was inhibited by 2-chloroacetic acid (MCA) and 2,2
      dichloroacetic acid (DCA). The inhibition pattern suggested a mixed type
      inhibition which was predominantly uncompetitive. Amino acid modification
      experiments demonstrated that one or more cysteine and arginine residues are
      likely to be involved in catalysis or play an important role in the maintenance
      of the enzyme structure. The characteristics of the DehA enzyme are compared to
      those of previously reported haloalcohol dehalogenases and discussed in terms of
      diversity of this type of dehalogenase.

PMID- 9621449
TI  - Molecular cloning and characterization of an endoxylanase gene of Bacillus sp. in
      Escherichia coli.
AB  - A gene encoding an endoxylanase of Bacillus sp. was cloned and expressed in
      Escherichia coli. The entire nucleotide sequence of a 1,620 bp SmaI fragment
      containing the endoxylanase gene was determined. The endoxylanase gene was 639 bp
      long and encoded 213 amino acids which showed up to 96% amino acid homology with
      other endoxylanases. The endoxylanase produced by E. coli harboring pKJX4 was
      purified by ion-exchange chromatography (DE-52 and CM-52) and its N-terminal
      sequence was determined to be Ala-Gly-Thr-Asp-Tyr-Trp-Gln-Asn-Trp-Thr-Asp-Gly-Gly
      Gly-Thr. The endoxylanase expressed in E. coli was identical to that of the
      original Bacillus sp. whose molecular weight was approximately 20,400. Most of
      the produced endoxylanase was localized in the periplasmic space of E. coli. When
      the endoxylanase was reacted with 2% oat spelts xylan (w/v) at 40 degrees C for
      10 h, the major product was xylobiose which is known to be a selective growth
      stimulant to one of the healthy intestinal microflora, Bifidobacteria.

PMID- 9621450
TI  - Bufadienolides from animal and plant sources.

PMID- 9621451
TI  - Alcohol dehydrogenases from olive (Olea europaea) fruit.
AB  - Alcohol dehydrogenase activity was detected in extracts from the pericarp tissues
      of developing olive fruits using hexanal as the substrate. Total activity in the
      crude extract was 20-fold higher with NADPH than with NADH. Three discrete
      enzymes were resolved by means of a purification protocol involving ammonium
      sulfate fractionation followed by ion-exchange and affinity chromatography. One
      of the enzymes was NAD-dependent and displayed a high K(m) for hexanal (K(m) =
      2.1 mM). Two NADP-dependent alcohol dehydrogenases were resolved, one showing a
      high K(m) for hexanal (K(m) = 1.9 mM) and the second with a lower K(m) for the
      same substrate (K(m) = 0.04 mM). The three enzymes have been partially purified
      and their kinetic parameters and specificities for various aldehydes determined.
      The involvement of these enzymes in the biogenesis of six carbon alcohols
      constituent of the aroma of olive oil is discussed.

PMID- 9621452
TI  - A cell wall-bound beta-glucosidase from germinated rice: purification and
      properties.
AB  - A large portion of beta-glucosidase (EC 3.2.1.21) in germinating rice seeds,
      which appears to be ionically bound to cell walls, can be solubilized with 1 M
      NaCl. Its activity increased more than eight-fold within five days of
      germination. It was purified to electrophoretic homogeneity from the extracts of
      germinated rice seeds by fractionation with (NH4)2SO4 followed by CM-Sepharose,
      Polybuffer exchanger 118, Concanavalin A-Sepharose and Bio-Gel P-100. The Mr of
      the purified enzyme, estimated by SDS-PAGE, was 56,000 and the isoelectric point
      was > 10.0. Its N-terminal amino acid sequence (44 residues) exhibited high
      homology to those of beta-glucosidases from other plants, such as barley and
      white clover. Its activity was optimal at pH 4.5 and 50 degrees, and it was
      strongly inhibited by glucono-1,5-lactone. The enzyme showed hydrolytic as well
      as transglycosylation activity towards (1-->3)-beta- and (1-->4)-beta-linked
      oligosaccharides with degree of polymerization of 2-4. The results suggest that
      the beta-glucosidase is probably involved not only in hydrolysis but also in
      modification of oligosaccharides in cell walls of germinating rice seeds.

PMID- 9621453
TI  - The interaction of shikimic acid and protein phosphorylation with PEP carboxylase
      from the C4 dicot Amaranthus viridis.
AB  - Shikimic acid has been described as a potent competitive inhibitor of the
      activity of C4 phosphoenolpyruvate carboxylase (PEPC) from Amaranthus viridis. In
      the present study, the effects of shikimic acid were examined further with the
      dephospho (dark-form) and in vitro phosphorylated forms of homogeneous PEPC from
      A. viridis. Kinetic analysis showed that the inhibitor effect of shikimic acid
      was dependent on the phosphorylation state of the enzyme. Thus, the I50 value of
      shikimic acid for dark-form PEPC was six times lower than that for the
      phosphorylated enzyme (12 vs 71 microM, respectively). When Glc6P, an activator
      of C4 PEPC, was present in the assay medium, the I50 value increased 2- and 3
      times with the phospho and dephospho PEPC-forms, respectively. Shikimic acid also
      markedly decreased 32P incorporation from Mg[gamma-32P]ATP into the dark-form of
      C4 PEPC, but not casein, catalyzed by protein kinase A. In this way, shikimic
      acid mimics the behaviour of L-malate, a well-known inhibitor of PEPC, in that it
      decreases both the enzyme's activity and phosphorylatability. Based on these
      data, a possible role for shikimic acid in the regulation of PEPC activity in
      plants is suggested.

PMID- 9621454
TI  - Characterization of a second calcium-dependent protein kinase from winged bean.
AB  - In plants, Ca2+ has emerged as the predominant second messenger for signal
      transduction, as cyclic nucleotides are not known to play any significant role in
      this system. Earlier, we characterized an interesting Ca(2+)-dependent protein
      kinase, WbCDPK (winged bean calmodulin-like domain protein kinase), from the
      soluble fraction of winged bean (Psophocarpus tetragonolobus) shoot extract. Here
      an isoform of WbCDPK is purified to apparent homogeneity from the same winged
      bean shoot extract. It is a single polypeptide chain protein-serine kinase,
      having an M(r) of about 70,000 and like WbCDPK, its preferred substrates are
      histone H1, syntide 2 and MLC-peptide (a synthetic myosin light chain related
      peptide) and it is totally dependent on Ca2+ for its activity, but exogenous
      calmodulin (CaM) does not stimulate it. However, it is strongly inhibited by CaM
      antagonists, indicating the presence of a CaM-like domain, as in WbCDPK. The two
      enzymes do not cross react immunologically and the isoform differs significantly
      from WbCDPK in its apparent inability to catalyse the autophosphorylation
      reaction, which is known to cause down-regulation of substrate phosphorylation in
      the case of WbCDPK.

PMID- 9621455
TI  - Involvement of protein kinase and G proteins in the signal transduction of
      benzophenanthridine alkaloid biosynthesis.
AB  - We have previously reported that elicitor-induced benzophenanthridine alkaloid
      biosynthesis in suspension-cell cultures of Sanguinaria canadensis L. (SCP-GM) is
      mediated by a signal transduction system that involves calcium and possibly
      protein kinase(s). In this work, a number of exogenous agents were employed to
      further investigate the components of the signal transduction pathway involved in
      the induction of alkaloid biosynthesis by a fungal elicitor and abscisic acid
      (ABA). SCP-GM suspension-cells were treated with compounds that modify protein
      kinase activity, including phorbol esters, and 1-oleoyl-2-acetyl-rac-glycerol
      (OAG), a synthetic diacylglycerol analogue. Phorbol-12-myristate-13-acetate
      induced alkaloid accumulation by as much as 65-fold over control values, while
      the negative control, phorbol-13-monoacetate, had no effect. OAG also increased
      alkaloid production by approximately 25-fold as compared to controls. Likewise,
      pretreatment of the suspension-cell cultures with H-7 or staurosporine,
      significantly suppressed ABA- or fungal-induction of benzophenanthridine alkaloid
      biosynthesis. Modulators of GTP-binding protein activity were also active in this
      system. Treatment of the suspension-cells with cholera toxin (CHX) induced
      alkaloid accumulation by 25-fold, which increased to 34-fold when CHX was
      combined with a fungal elicitor derived from Penicillium expansum (PE), and 32
      fold when CHX was combined with ABA. Treatment of SCP-GM cells with CHX also
      enhanced the activities of two N-methyltransferases in the benzophenanthridine
      biosynthetic pathway namely, tetrahydroberberine-N-methyltransferase and
      tetrahydrocoptisine-N-methyltransferase, by six and seven fold, respectively.
      Furthermore, benzophenanthridine alkaloid biosynthesis was induced by treating
      the suspension-cells with the G-protein activators, mastoparan, mas-7 or
      melittin, while the inactive homologue, mas-17, did not. Suppression of alkaloid
      accumulation occurred when the suspension-cells were treated with GDP beta S or
      pertussis toxin prior to treatment of the SCP-GM cells with either PE or ABA. The
      results support the hypothesis that one or more protein kinases, and putative G
      proteins are involved in the signal transduction pathway that mediates ABA and
      fungal-induced benzophenanthridine alkaloid biosynthesis.

PMID- 9621456
TI  - Induction of furanocoumarin biosynthesis in Glehnia littoralis cell suspension
      cultures by elicitor treatment.
AB  - Cell suspension cultures were established from Glehnia littoralis plants
      belonging to two different geographic strains. When the cells were treated with
      yeast extract, they started to produce and excrete furanocoumarins into the
      culture medium; a major component, bergapten, and a minor one, xanthotoxin, were
      detected and identified by HPLC and GC/MS. Changes in phenylalanine ammonia-lyase
      (PAL) activity and furanocoumarin production after elicitor treatment were
      traced, showing that PAL activity increased rapidly, reached a maximum after 24
      h, and then declined to the normal level after 96 h which preceded the induced
      bergapten production. The induced-PAL activity of the cultured cells established
      from an S-type plant which accumulated trace amounts of furanocoumarins was about
      50% of that in the cultured cells from an N-type plant that accumulated more than
      0.1% furanocoumarins in the underground parts. However, the elicited production
      of bergapten was about six times higher in the cell cultures from the S-type
      plant. Addition of the PAL inhibitor 2-aminoindan-2-phosphoric acid (AIP) at 10
      microM suppressed the induction of PAL activity and furanocoumarin production.

PMID- 9621457
TI  - Mode of antibacterial action of retrochalcones from Glycyrrhiza inflata.
AB  - Licochalcone A-D and echinatin, retrochalcones isolated from the roots of
      Glycyrrhiza inflata, showed antimicrobial activity. Among them, licochalcone A
      and C had potent activity against some Gram-positive bacteria. These
      retrochalcones inhibited oxygen consumption in susceptible bacterial cells. The
      oxidation of NADH in bacterial membrane preparations was also inhibited by them.
      NADH-cytochrome c reductase was inhibited by licochalcones, while cytochrome c
      oxidase was not. NADH-CoQ reductase and NADH-FMN oxidoreductase were not
      inhibited. The site of respiratory inhibition of licochalcones was thought to be
      between CoQ and cytochrome c in the bacterial respiratory electron transport
      chain.

PMID- 9621458
TI  - Triterpenoid saponins from Quillaja saponaria.
AB  - Three new saponins were isolated from a commercial bark extract of Quillaja
      saponaria Molina. These compounds were also obtained as degradation products from
      larger saponins in this extract when treated with strong alkali. The compounds
      were characterized, using mainly NMR spectroscopy, mass spectrometry and chemical
      methods, as quillaic acid 3-O-?beta-D-galactopyranosyl-(1-->2)-beta-D
      glucopyranosiduronic acid?, 3-O-?alpha-L-rhamnopyranosyl-(1-->3)-[beta-D
      galactopyranosyl-(1-->2)] -beta-D-glucopyranosiduronic acid? and 3-O-?beta-D
      xylopyranosyl-(1-->3)-[beta-D-galactopyranosyl -(1-->2)]-beta-D
      glucopyranosiduronic acid?, respectively.

PMID- 9621459
TI  - Strategies to improve plant resistance to bacterial diseases through genetic
      engineering.
AB  - Many different genetic strategies have been proposed to engineer plant resistance
      to bacterial diseases, including producing antibacterial proteins of non-plant
      origin, inhibiting bacterial pathogenicity or virulence factors, enhancing
      natural plant defenses and artificially inducing programmed cell death at the
      site of infection. These are based on our knowledge of the mechanisms of action
      of antibacterial compounds and of the successive steps in plant-bacterial
      interactions. This article presents the different approaches and demonstrates
      that, even though several of these ideas have already been applied, no commercial
      applications have yet been achieved.

PMID- 9621460
TI  - Combinatorial biocatalysis: a natural approach to drug discovery.
AB  - Nature's most potent molecules are produced by enzyme-catalysed reactions,
      coupled with the natural selection of those products that possess optimal
      biological activity. Combinatorial biocatalysis harnesses the natural diversity
      of enzymatic reactions for the iterative synthesis of organic libraries.
      Iterative reactions can be performed using isolated enzymes or whole cells, in
      natural and unnatural environments, and on substrates in solution or on a solid
      phase. Combinatorial biocatalysis is a powerful addition to the expanding array
      of combinatorial methods for the generation and optimization of lead compounds in
      drug discovery and development.

PMID- 9621461
TI  - Aequorea victoria bioluminescence moves into an exciting new era.
AB  - Bioluminescence has revolutionized research into many cellular and molecular
      biological processes, ranging from intracellular signalling to gene
      transcription. This article focuses on the chemistry and biotechnological
      exploitation of the two proteins involved in bioluminescence of the jellyfish
      Aequorea victoria--aequorin and green fluorescent protein. Engineered recombinant
      aequorin has led to a novel technological approach to monitoring calcium signals
      in organelles and subcellular domains. A new generation of intracellular calcium
      indicators has been produced in which engineered variants of green fluorescent
      protein are used to probe their ionic environment using intramolecular
      fluorescence-resonance-energy transfer.

PMID- 9621462
TI  - Development of biocompatible synthetic extracellular matrices for tissue
      engineering.
AB  - Tissue engineering may provide an alternative to organ and tissue
      transplantation, both of which suffer from a limitation of supply. Cell
      transplantation using biodegradable synthetic extracellular matrices offers the
      possibility of creating completely natural new tissues and so replacing lost or
      malfunctioning organs or tissues. Synthetic extracellular matrices fabricated
      from biocompatible, biodegradable polymers play an important role in the
      formation of functional new tissue from transplanted cells. They provide a
      temporary scaffolding to guide new tissue growth and organization, and may
      provide specific signals intended to retain tissue-specific gene expression.

PMID- 9621463
TI  - Negative-strand RNA viruses: applications to biotechnology.
AB  - The establishment of reverse-genetics techniques to manipulate the genome of
      negative-strand RNA viruses has contributed enormously to a better understanding
      of the replication mechanisms and pathogenicity of this group of viruses. The
      generation of recombinant viruses bearing specific mutations in the coding and
      noncoding regions of their genomic RNAs now allows the functions in the
      replicative cycle of specific RNA regions and protein domains of these viruses to
      be studied. In addition, recombinant negative-strand RNA viruses can now be
      designed to have specific properties that make them attractive biotechnological
      tools.

PMID- 9621464
TI  - [Strategy for allergy treatment with IgE-Fc epsilon RI-mast cell axis as the
      target].

PMID- 9621465
TI  - [Prescription for mind].

PMID- 9621466
TI  - [Emergency medical care for allergic disorders, especially for adult asthma].

PMID- 9621467
TI  - [Effect of pharmacist's instruction on the treatment of asthmatics with inhaled
      steroid].
AB  - Pharmacist's instruction is provided to asthmatic patients who received an
      inhaled steroid in Hamamatsu University Hospital. We studied influences of
      pharmacist's instruction on the repeutic effects of an inhaled steroid,
      beclomethasone dipropionate (BDP). In 29 patients who had been treated with
      inhaled BDP under the physician's instruction for more than 3 months, we examined
      drug compliance, correctness of inhalation procedure and treatment score, symptom
      score, peak expiratory flow (PEF) values, and compared these before and after the
      instruction. The instruction was repeatedly provided at an interval of about one
      month. Patients who followed the indicated regimen were 55.2 and 93.1% before and
      after the instruction, respectively. An appropriate inhalation maneuver was
      respectively. An appropriate inhalation maneuver was performed in 24.1 and 93.1%
      of patients before and after the instruction, respectively. PEF values increased
      by 12.9 +/- 9.3% (mean +/- standard deviation, p < 0.01) after the instruction.
      In conclusion, pharmacist's repeated instruction enhanced the therapeutic effects
      of inhaled BDP in patients with asthma.

PMID- 9621468
TI  - [Measurement of expired nitric oxide concentration].
AB  - Much interest has been focused on standardization of measurement of expired
      nitric oxide (NO) concentration. The aim of this study was establish a simple
      measurement of expired NO concentration. SUBJECTS AND METHODS: This study
      included 5 healthy male adults. To clarify whether NO is excreted in expired air
      constantly, its concentrations were measured while changing the flow rate. To
      examine the influence of NO derived from the nasal cavity, we compared expired No
      concentrations sampled from the month with those sampled from the endotracheal
      tube inserted to the trachea at a constant flow rate serially. RESULTS: Expired
      NO concentrations decreased in inverse with the flow rate. No may be serially
      excreted in expired air. When serial changes of expired No concentrations sampled
      from the mouth were examined, its NO concentration initially reached a peak, then
      showed a plateau. Serial changes of those sampled from the endotracheal tube
      showed only a plateau. Plateau levels were not different between the two kinds.
      Therefore the peak values may have been influenced by NO derived from the nose
      that fell in the trachea by inspiration. Plateau values appeared to represent
      airway and lung-derived NO. CONCLUSIONS: A simple measurement of expired NO
      concentration should be sampled from the mouth at a constant flow rate serially.
      Evaluating plateau values is appropriate for expired NO concentration.

PMID- 9621470
TI  - [A clinical evaluation of clustered immunotherapy in house-dust-mite-sensitive
      adult bronchial asthma].
AB  - Clustered immunotherapy (C-IT) using house-dust (HD) antigen was performed in
      eight HD-mite-sensitive adult bronchial asthmatics. Six mg of mequitazine was
      given 2 hours before each visit. For each visit, injections of antigen were
      performed four times with an hour interval. Either 0.1 ml of 10-fold
      concentration of the HD or a final dose at the end of the fifth week was
      determined as a maintenance dose. All cases have reached to ten-fold
      concentration of the HD antigen within 5 weeks and been able to introduce
      maintenance therapy without any systemic reaction. Following C-IT, a rapid
      increase in morning peak expiratory flow rate was observed which is followed by
      decrease in clinical scores. Furthermore, an increase in mite-specific IgG4
      antibody and a decrease in peripheral blood eosinophils were observed 16 weeks
      following C-IT. These results suggest that C-IT using HD antigen can be performed
      safely and securely and provides rapid immunological responses as well as
      clinical benefit in HD-mite-sensitive adult asthmatics.

PMID- 9621469
TI  - [Epidemiological study of allergic rhinitis in different districts].
AB  - We investigated the morbidity of allergic rhinitis in downtown, rural area and
      fishing village by questionnaire in October, 1996. The morbidity rate of allergic
      rhinitis was 35.7% (370 subjects out of 1036) in downtown, 27.5% (266 out of 966)
      in rural area and 12.9% (273 out of 2112) in fishing village, and that of adult
      was 36.2% (314 out of 868) downtown, 28.9% (137 out of 474) in rural area and
      12.07% (199 out of 1649) in fishing village, and that of child was 33.3% (56 out
      of 168) in downtown, 26.22% (129 out of 492) in rural area and 15.98% (74 out of
      463) in fishing village. The morbidity of Japanese cedar pollinosis was 17.37%
      (180 out of 1036) in downtown, 13.77% (133 out of 966) in rural area and 2.60%
      (55 out of 2112) in fishing village. There was statistical difference (p < 0.001)
      between the each district respectively. It was proved that the morbidity of
      allergic rhinitis in downtown was higher than the rural area or fishing village,
      and that in fishing village was the lowest in these districts.

PMID- 9621471
TI  - [The correlation between the outbreaks of asthma attack and meteorologic
      parameters in Okinawa].
AB  - The correlation between the outbreaks of asthma attack and meterologic parameters
      was analyzed in Okinawa island which belongs to the subtropics. The epidemiologic
      outbreaks of asthma was investigated for 2 years from the asthma diaries
      described by 27 patients. The severity of asthma attack was expressed as the
      asthma score on the basis of asthma diaries. The number of patients carried to
      hospitals by ambulance on asthma attacks was investigated for 3 years. Two-by-two
      contingency tables were computed for the meteorologic parameters and analyzed
      with the method of chi-square test. From the view point of asthma scores, the
      total scores of 27 patients were increased when a mean and a minimum temperature
      were respectively higher than each mean value in the period of investigation (p <
      0.05, respectively). From the view point of the number of patients carried to
      hospitals by ambulance on asthma attacks, it was suggested that asthma attacks
      tended to occur when a mean, a maximum and a minimum temperature, and a vapor
      pressure were lower than each mean value (p = 0.0001, p = 0.0001, p = 0.0001, p =
      0.0002), and a barometric pressure was higher than a mean value in the period of
      investigation (p = 0.0016). From the further analysis of these data by multiple
      regression analysis, it was suggested that the number of patients carried to
      hospitals by ambulance on asthma attacks was influenced by low temperature. In
      addition, it was suggested that the changes of meteorologic parameters on the
      passing over of typhoon, especially, the decrease of temperature and barometric
      pressure, were related to induce asthma attacks.

PMID- 9621472
TI  - [Measurement of Candida-specific lymphocyte proliferation by flow cytometry in
      children with atopic dermatitis].
AB  - To study a role of Candida albicans in the development of atopic dermatitis (AD)
      from the viewpoint of cellular responses, we measured Candida-specific lymphocyte
      proliferation by flow cytometry in children with AD. There was no apparent age
      dependent change in the level of Candida-SIF (stimulation index measured by flow
      cytometry) in either AD or non-atopic control subjects. The level of Candida-SIF
      was significantly higher in AD patients than in non-atopic controls (178.0 +/-
      89.3 vs 137.9 +/- 37.6, p < 0.02), and the incidence of subjects with the
      elevated Candida-SIF level (> or = 200) was significantly higher in AD patients
      than in non-atopic controls (27.9% (17/61) vs 2.6% (1/38), p < 0.005). There was
      no correlation between the levels of Candida-SIF and Candida-specific IgE
      antibody. These results suggest that Candida albicans contributes to the
      development of AD in some patients not only by Type I, but also by Type IV
      hypersensitivity reactions.

PMID- 9621473
TI  - [Cough variant asthma among patients with chronic persistent cough and its
      clinical outcome].
AB  - Thirty-nine patients with chronic persistent cough continuing more than eight
      weeks were examined regarding to their airway responsiveness to methacholine
      challenge using the Astograph (TCK-6100H, Chest Corp. Japan). Of these, twenty
      three individuals (59%) had airway hyperresponsiveness, leading to diagnose as
      having cough variant asthma (CVA). Patients with CVA had a higher percentage of
      eosinophils in peripheral blood and a lower forced expiratory volume in one
      second than those in non-CVA group. Furthermore, four patients (17%) developed
      the classic signs and symptoms of asthma, whereas 7 cases (30%) resolved their
      cough without further treatment and 12 cases (52%) continued to have CVA. These
      data suggested that a significant proportion of patients with chronic persistent
      cough had CVA and some of them may develop to classic wheezing asthma.

PMID- 9621474
TI  - Induction of labor by intracervical prostaglandin gel and oxytocin infusion in
      primigravid women with unfavorable cervix.
AB  - The rate of Cesarean Section for failed induction of labor and maternal and fetal
      compilations are high when labor is induced in a nulliparas women with an unripe
      cervix by amniotomy and oxytocin infusion. Prostaglandins (PG) in different forms
      have been used for ripening the cervix with an aim of reducing these problems. A
      prospective randomized trial was performed on one hundred primigravid women
      between 37 and 42 weeks of gestation with singleton pregnancy, cephalic
      presentation and unfavorable cervix (Modified Bishop Score < or = 5) in the
      department of Obstetrics & Gynaecology of Institute of Postgraduate Medicine &
      Research from 1st May 1996 to 30th April 1997. In this study the efficiency of
      prostaglandin E2 intracervical (PGE2 IC) gel in induction of labor in a group of
      primigravid women with unripe cervix was assessed and compared with another group
      with similar characteristics using oxytocin infusion and artificial rupture of
      membrane (ARM). The Modified Bishop Score (MBS), interval between IOL and onset
      of labor and the duration of labor after insertion of PGE2 gel was significantly
      different from those of oxytocin infusion group. But the Apgar Score at 1 & 5 min
      had shown no statistically significant difference. Any significant difference
      could also not be detected in the mode of delivery between the two induction
      group. The proportion of emergency Cesarean Section (CS) was high in the oxytocin
      infusion group than that of in the prostaglandin group. There was also no
      significant difference regarding the acceptability of both the induction methods.

PMID- 9621475
TI  - Efficacy of methotrexate in rheumatoid arthritis.
AB  - Rheumatoid arthritis is a common inflammatory articular disorder in Bangladesh.
      Methotrexate has proved to be an effective and relatively safe disease modifying
      drug for this disease. A quasiexperimental trial of the efficacy of methotrexate
      in rheumatoid arthritis was carried out in the Rheumatology Clinic, Institute of
      Postgraduate Medicine & Research, Dhaka during the period between July 1992 and
      September 1993. Thirty eight patients fulfilling the revised ARA criteria were
      given methotrexate in a total weekly dose of 7.5 to 15 mg. They were followed up
      at weekly intervals for one month and then monthly for a total duration of six
      months. Twenty three subjects eventually completed the trial. The trial showed
      significant differences in the disease activity indices at the end of six months.
      The decline of activity was noted at the end of one month. As a whole the
      response was complete in 4(17%), marked in 14(61%), moderate in 4(17%) and nil in
      1(4%). Adverse effects occurred in 27 subjects. They were mild and transient in
      22. Methotrexate appeared to be an acceptable DMARD for our rheumatoid arthritis
      population.

PMID- 9621476
TI  - Immunofluorescent microscopic findings in glomerulonephritis.
AB  - Histopathology and direct immunofluorescence (DIF) microscopy were performed on
      renal biopsy specimens of 60 clinically suspected cases of glomerulonephritis
      (GN). Histopathological diagnosis was obtained in 44 (73.3%) cases and immune
      complex deposition were detected by DIF in 28 (46.7%) cases. Immune complex
      deposition were observed in all cases of membranous GN, systemic lupus
      erythematosus (SLE), and rapidly progressive GN (RPGN), most of the cases of
      diffuse proliferative GN (2 out of 3) mesangioproliferative GN (12 out of 15) and
      focal glomeruloscleros is (3 out of 5 cases). No immune deposits were observed in
      minimal change GN, chronic GN, and diabetic nephropathy. Histopathological
      diagnosis was not obtained in 16 (26.7%) cases, 3 (5%) of which showed immune
      complex deposition by DIF. Anti-GBM nephritis was demonstrated in one (3.6%)
      case, the rest were immune complex nephritis.

PMID- 9621477
TI  - Chemotherapy of acute myeloblastic leukaemia with DAM regimen.
AB  - 32 patients of denovo-ANLL were treated with Doxorubicin, Ara-C and 6
      Mercaptopurine (DAM) regimen. Remission induction was instituted with 1-3 cycles
      of DAM regimen and maintenance was given by 6-MP continuously with intermittent
      DA (1,5) regimen. In the remission induction, Doxorubicin 30 mg/m2 for 3 days,
      Ara-C 150 mg/m2 for 5 days and 6-Mp 100 mg/m2 daily was given. Complete remission
      (CR) was observed in 60% cases. The probability of 2 years disease-free survival
      of patients with complete remission is 56.73%.

PMID- 9621478
TI  - Cut throat injury: a retrospective study of 26 cases.
AB  - Cut throat injuries and associated deaths are common in our society. Majority
      succumb to their injuries. In this study, the hospital records of twenty six such
      cases (13 M & 13 F) were reviewed. Eleven victims were in their third decade.
      Eighteen cases came from poor socio-economic class. Eleven had suicidal, eleven
      homicidal and four accidental injuries. Familial troubles, psychiatric illness
      and poverty were the triggering factors in suicidal attempts. The motives of
      homicide included political conflict, sex related crimes, dacoity, familial, land
      related disputes, etc. All had their hypopharynx and/or larynx exposed.
      Tracheostomy was done in fifteen cases. All but two had uneventful recovery. One
      died in the hospital due to hemorrhage, shock and asphyxia from aspirated blood.
      It was observed that appropriate measures could save lives in vast majority.

PMID- 9621479
TI  - Multiple papilloma of the larynx in an adult--a case report.
AB  - Multiple papilloma of the larynx commonly affects the juvenile subjects. Only a
      few adult cases have been reported. Such a rare case in Bangladesh, is reported
      here. Twenty five years old one male patient was admitted into Sir Salimullah
      Medical College & Mitford Hospital with the complaints of hoarseness of voice &
      dysponea. He was diagnosed as papilloma clinically and histopathologically, and
      treated with tracheostomy & microlaryngoscopic excision of the masses. The
      patient was readmitted after 3 months with recurrence of papilloma at the same
      site and the growth was excised under anaesthesia. The past history of his
      illness revealed that he underwent to more surgeries for the same condition. The
      patient was lost to follow up.

PMID- 9621480
TI  - Cardiotoxicity and cardioprotection in breast cancer chemotherapy. The role of
      dexrazoxane.

PMID- 9621481
TI  - [High-dose chemotherapy of breast cancer with hematopoietic protection; current
      status and prospectives].

PMID- 9621482
TI  - [Fifth Conference on Retrovirus and Opportunistic infections. 1-5 February 1998,
      Chicago, USA].

PMID- 9621483
TI  - Dexrazoxane cardioprotection in advanced breast cancer patients undergoing high
      dose epirubicin treatment.
AB  - PURPOSE: We performed a randomized trial to evaluate the cardioprotective effect
      of dexrazoxane (DEX) in advanced breast cancer patients (ABC) treated with high
      single-dose epirubicin (EPI). A secondary objective was to determine the role of
      radioimmunoscintigraphy (RIS) in the assessment of epirubicin cardiotoxicity.
      PATIENTS AND METHODS: Ninety-five patients with ABC were treated with EPI 160
      mg/m2 by i.v. bolus every 3 weeks with or without DEX, 1,000 mg/m2 i.v. Cardiac
      monitoring included multigated radionuclide (MUGA) scan with determination of
      resting left ventricular ejection fraction (LVEF), and RIS with 111-Indium
      antimyosin monoclonal antibodies. RESULTS: The overall response rate was 69% in
      the EPI arm and 67% in the EPI + DEX arm; median time to response and median time
      to progression were identical in both arms, being 2 and 8 months, respectively.
      Median survival was 19 months versus 29 months (p 0.21), respectively. DEX did
      not appear to contribute to extracardiac EPI toxicity. Congestive heart failure
      occurred only in the EPI arm (2 instances). LVEF significantly decreased from
      baseline only in the EPI group. An abnormal tracer uptake at RIS was observed
      early in both arms, but the increase in heart to lung ratio was much more evident
      in the control group. CONCLUSIONS: DEX significantly protects against the
      development of high dose epirubicin cardiotoxicity apparently without evidence of
      an adverse impact on antitumor activity and non cardiac toxicity. RIS is a very
      sensitive technique in detecting anthracycline cardiac damage, but its
      specificity is low and cannot be considered alone a primary test for guiding
      anthracycline treatment.

PMID- 9621484
TI  - [High dose chemotherapy in metastatic carcinoma of the breast].
AB  - PURPOSE: To verify tolerance and clinical efficacy of high-dose chemotherapy
      (HDCT) in metastatic breast cancer (MBC). PATIENTS AND METHODS: We submitted to
      HDCT with autologous peripheral blood cells transplant 66 patients, with MBC
      responding to induction chemotherapy. The condizioning regimen was ICE:
      iphosphamide 3.3 g/m2 dd. -8/-6, carboplatin 450 mg/m2 plus etoposide 400 mg/m2
      dd. -5/-3 (21 patients = 78%); CTM: cyclophosphamide 100 mg/kg dd. -4/-3,
      tyothepa 500 mg:m2 d.-5, mytoxantrone 40 mg/m2 d. -6 (6 patients, 22%). RESULTS:
      Median number of aphereses was 2 (range 1-5), median amount of CD34+ cells/kg bw
      of 10 x 10E6 (range 3.5-38.2). Median recovery time was 10th day for PMN (range 8
      37) while for platelets it was 9th day (range 8-37): total hospital stay was of
      24 days (range 22-48). After induction therapy we had PR in 13/27 metastatic
      patients (48%) and CR in 14/27 (52%). After conditioning treatment we had PR in
      12/27 (44%) and CR in 15/27 (56%). Median time to progression was 19 months
      (range 7-38) and median survival 52 months (range 7-59+), with 30% surviving
      beyond 4 years. CONCLUSIONS: Feasibility of HDCT in advanced breast cancer seems
      verified. The promising results need to be confirmed.

PMID- 9621485
TI  - Role of prognostic factors in the therapeutic strategy of primary gastric non
      Hodgkin's lymphomas.
AB  - PURPOSE: To evaluate retrospectively in 64 gastric non-Hodgkin lymphoma (G-NHL)
      patients the role of some prognostic factors in the therapeutic strategy of this
      disease. PATIENTS AND METHODS: Sixty-four primary G-NHL patients (39 males and 25
      females; median age: 57 years) were retrospectively evaluated. Treatment
      consisted of surgery alone (S) in 7 patients, chemotherapy alone (CT) in 15, CT +
      radiotherapy (RT) in 2, S + RT in 2, S + CT in 19, S + CT + RT in 16. Three
      patients had no treatment. Forty-four patients received sub-total gastrectomy
      (21) or total gastrectomy (23), and 20 were not submitted to surgery. RESULTS:
      After a median follow-up of 106 months (range 48-201), the four-year disease free
      survival (DFS) was 56% and overall survival (OS) was 59%. In the univariate
      analysis, tumor invasion depth (p = 0.007), stage (IIE1 vs IIE2: p = 0.007; I
      IIE1 vs IIE2-IV: p = 0.0000009) and treatment (in stage IE-IIE1: p = n.s.; in
      stage IIE2-IV: p = 0.002) were significantly different. In the multivariate Cox
      regression model, stage was the only significant variable negatively influencing
      survival. CONCLUSIONS: Our study confirms the prognostic value of both the depth
      of invasion and the disease stage. In patients with early disease stages and
      disease localized to the gastric wall, a conservative approach can be
      recommended. No difference was found between the sub-total and total gastrectomy
      but surgery retains its fundamental role for G-NHL, even in advanced disease.
      Prospective trials are needed to confirm these results.

PMID- 9621486
TI  - [Ectopic thyroid and late-onset functional deficit of the thyroid gland].
AB  - PURPOSE: To evaluate retrospectively the incidence of ectopic thyroid gland
      causing hypothyroidism in patients referred to "Di Venere" Hospital, Bari.
      PATIENTS AND METHODS: Over a period of 14 years, ectopic thyroid gland has been
      detected by thyroid scan in 56 out of 122 patients with hypothyroidism due to
      congenital thyroid abnormalities. Of these 56 patients, 48 were < 1 year old, 2
      were < 2 years old, while 8 with late onset of the disease were 7 to 35 years
      old. RESULTS: Among the eight patients with late onset hypothyroidism, 3 had
      normal serum levels of thyroid hormones at birth. Overall, an ectopic thyroid
      gland was observed in 6 out of 32 (18.7%) patients with hypothyroidism beginning
      between 2.5 and 14 years of age. CONCLUSIONS: Thyroid scan is a safe and
      effective procedure in the diagnosis of ectopic thyroid gland in neonatal
      patients. It should be recommended as neonatal screening in order to prevent
      irreversible damage to central nervous system.

PMID- 9621487
TI  - [Correlation between HIV-inhibiting drug activity in human macrophages and
      clinical outcome].
AB  - PURPOSE: To assess the comparative efficacy of drugs inhibitors of human
      immunodeficiency virus (HIV) in human macrophages and lymphocytes, and to
      correlate the results with the clinical outcome. MATERIALS AND METHODS: Human
      primary macrophages and lymphocytes were infected with HIV in the presence of the
      following HIV inhibitors, all currently in clinical use: zidovudine, stavudine,
      zalcitabine, didanosine, lamivudine, PMEA, PMPA (all inhibitors of HIV reverse
      transcriptase), saquinavir and U-75875 (inhibitors of HIV protease). RESULTS: All
      reverse transcriptase inhibitors tested showed a markedly higher antiviral
      activity in macrophages than in lymphocytes. Also protease inhibitors have a
      substantial anti-HIV activity in macrophages, yet their efficacy is markedly
      diminished if the drugs are added to macrophage culture after HIV, that is when
      the virus has established a chronical infection. Under these experimental
      conditions, however, only protease inhibitors among all HIV-inhibitors in
      clinical use are able to decrease virus replication in chronically-infected
      macrophages. CONCLUSIONS: The results have strong clinical implications, due to
      the important role of macrophages in the pathogenesis of HIV infection.
      Macrophages are the major source of HIV at extralymphoid tissue levels,
      particularly in the central nervous system, where the blood-brain barrier
      strongly limits the penetration of antiviral drugs. For these reasons, only
      drugs, like stavudine and zidovudine, provided with good anti-HIV activity in
      macrophages, and reasonable barrier penetration have substantial chances to be
      effective in the central nervous system, and thus affect virus replication in a
      sanctuary where HIV hides and replicates out of the control of the immune system.

PMID- 9621488
TI  - Platinum compounds as radiosensitizers in strontium-89 metabolic radiotherapy.
AB  - PURPOSE: Strontium-89 is currently used for the treatment of painful bone
      metastases. This study reports on two preliminary experiences with low-dose
      platinum compounds, carboplatin and cisplatin, as radiosensitizers in 89Sr
      therapy. PATIENTS AND METHODS: 30 patients entered the carboplatin study: 15
      patients (Group A) were treated with 148 MBq 89Sr followed by carboplatin (100
      mg/m2 at 7 and 21 days) and 15 patients (Group B) were treated with 89Sr alone.
      12 patients entered the cisplatin study: six patients (Arm 1) received 148 Mq
      89Sr plus cisplatin (50 mg/m2) in two administrations (immediately before and 10
      days after 89Sr injection) and six patients (Arm 2) received 89Sr plus two
      placebo administrations. Pain response was assessed 8 weeks after the therapy on
      the Wisconsin score modifications. RESULTS: No clinically significant adverse
      effects or myelosuppression by platinum compounds were observed. In carboplatin
      study a pain response was observed in 20 of 27 (74%) evaluable patients, 13/15 in
      group A and 7/12 in group B. The pain response in the patients treated with 89Sr
      and carboplatin was clearly superior to that seen in the patients treated with
      89Sr alone (P = 0.025), whereas survival was only marginally better in the
      combined treatment group (8.1 vs 5.7 months, P = 0.19). In cisplatin study a pain
      response was observed in 10 of 12 (83%) evaluable patients, 5/6 in Arm 1 and 4/6
      in Arm 2. CONCLUSIONS: Low-dose platinum compounds seem to enhance the effects of
      89Sr radioisotope therapy on pain from bone metastases without relevant
      hematological toxicity.

PMID- 9621489
TI  - [Monitoring of sE-selectin serum levels in three different dermatoses].
AB  - PURPOSE: To determine the behaviour of serum levels of soluble E-selectin (sE
      selectin), the soluble isoform of E-selectin, before/during/after therapy in
      patients with three. PATIENTS AND METHODS: Using commercially available ELISA
      kits, serum levels of sE-selectin have been determined in 15 patients with
      psoriasis, 15 with pemphigus vulgaris and 15 with bullous pemphigoid, and
      compared with those of 30 healthy subjects. RESULTS: The results showed increased
      serum levels of sE-selectin in the three groups of patients as compared with
      those of 30 healthy subjects (p < 0.01). In addition, serum levels were
      significantly correlated with the disease activity expressed as Psoriasis Area
      and Severity Index (PASI score) (R = 0.56, p = 0.014) in psoriasis, and as number
      of the visible lesions (blisters/erosions), in the two bullous dermatoses (R =
      0.81, p < 0.01). After therapy, the marker levels were significantly decreased (p
      < 0.01). CONCLUSIONS: Overall, these data suggest that serum determinations of sE
      selectin could represent a clinically useful indicator to monitor therapy.

PMID- 9621490
TI  - [Hepatic steatosis: clinical-statistical study of patients diagnosed by
      histological or ultrasonographic methods].
AB  - PURPOSE: This study wants to document eziopathogenetic factors and clinical,
      instrumental and hystological characters that associate to the various types of
      hepatic steatosis. PATIENTS AND METHODS: In this retrospective study have been
      examined two different groups of randomized patients. The "Group 1" comprehended
      70 patients with hystologic diagnosis of hepatic steatosis (steatohepatitis--SH-
      60%; steatosis--SE--40%). The "Group 2" comprehended 70 patients with
      ultrasonographic pattern of fatty liver (slight degree: 70%; severe degree: 30%).
      RESULTS: Analysis of results relative to the "Group 1" showed the role of HCV
      infection in etiopathogenesis of the SH, significantly greater than in SE (76.2%
      vs 25%; p < 0.0001). SE is often associated with exogenous noxae (alcoholism:
      28.6%; use of long-term medications: 14.3%) or metabolic disorders (hyperglycemia
      28.6%, hyperlipidemia 42.8%, obesity 25%). Haven't seen differences of clinical
      data or serum liver tests between SE and SH. Histological features that predicted
      the development of cirrhosis and/or fibrosis are more frequent in SH (SH: 40.4%
      vs SE: 10.7%; p < 0.01). The analysis of "Group 2" hasn't shown differences of
      clinical data or serum liver tests between slight and severe degree. CONCLUSIONS:
      Analysis of results relative to the two groups of patients ones has shown that SE
      and SH are thick asymptomatics and associated at hepatomegaly and at increase of
      ALT, AST, gamma GT. The increase of ALT and/or AST leads to search for the
      markers of HBV and HCV; when they are positive, hepatobiopsy is necessary for the
      diagnosis of possible SH or evolutive state to liver cirrhosis.

PMID- 9621491
TI  - [Vinorelbin in the treatment of breast cancer: current status and prospectives
      for the future].
AB  - PURPOSE: To evaluate efficacy and tolerability of vinorelbine in breast cancer.
      DESIGN: A review of most significant and recent clinical trials was performed.
      RESULTS: Vinorelbine as single agent showed 44% and 17.36% of response as 1st and
      2nd line treatment, respectively. When combined with other agents, these figures
      were the following: cisplatin, 73%-75% and 43-64%; mitomycin C, up to 92% and 33%
      69%; 5-fluorouracil, 33%-64% and 22%-55%; ifosfamide, 57% and 28%; taxol, 78% and
      54%; taxotere, up to 80%; mitoxantrone, 44%-68% and 31%-40%; doxorubicin, 57%-82%
      and 30%-33%; epirubicin, 22%-78% and 33%. Vinorelbine-epirubicin combination
      appears to be very active in neoadjuvant setting, with up to 92% response rates.
      CONCLUSIONS: Vinorelbine activity is significant and similar to that of the most
      active antineoplastic drugs in breast cancer. The most promising combinations
      appear to be with anthracyclines, taxanes or mitomycin C, even in heavily
      pretreated patients. Some aspects, such as optimal dose and scheduling and the
      inclusion in adjuvant programs or in new combination regimens remain to be
      defined.

PMID- 9621492
TI  - [Long-term survival after hepatectomy for metastatic liver cancer originating
      from colorectal carcinoma: presentation of two clinical cases].
AB  - We report two case histories of long surviving patients after resection of liver
      methastases from colorectal cancer. In the first case the patient underwent a
      right hepatectomy to resect a 3 cm-lesion revealed by a CT scan three years after
      surgery for a rectal adenocarcinoma. Subsequently, she received two cycles of 5
      day continuous infusion of fluorouracil. Four years and 11 months after
      hepatectomy, the patient is alive and free of disease. The second patient
      underwent resection of a large hepatic methastasis 3 months after left
      emicolectomy. The lesion substituted almost completely the right lobe and
      extended to the IV segment of the left lobe of the liver. After hepatectomy, the
      patient had a disease-free survival longer than 10 years, until a chest X-ray and
      a CT scan revealed a primary right lung cancer (citologically, adenocarcinoma)
      with a methastasis in the left lung. Surgical resection represents the only
      potentially curative therapy for hepatic methastases from colorectal cancer.
      Recent data about patient selection for hepatic methastasectomy are presented,
      and the opportunity of postoperative chemotherapy is discussed.

PMID- 9621493
TI  - [Discovery of the AIDS virus].

PMID- 9621494
TI  - National influenza surveillance 1997.
AB  - In 1997 information from several sources was combined to detect trends in
      influenza activity in Australia. Data was included from laboratories, general
      practitioners and a national employer. Laboratory surveillance documented two
      consecutive outbreaks, influenza B in July followed by influenza A (H3N2) in
      August. Some of the influenza A (H3N2) viruses isolated, represented by the
      A/Sydney/5/97 strain, showed significant antigenic drift from the A/Wuhan/359/95
      vaccine strain. Influenza activity was also reflected in the consultation rates
      recorded by sentinel general practitioner reporting schemes. The peak
      consultation rate recorded by the Australian Sentinel Practice Research Network
      was higher and later than in recent years, occurring in early August. Tropical
      Influenza Surveillance in the Northern Territory demonstrated an early outbreak
      in March followed by a second rise later in the year. There was no rise in
      absenteeism rates recorded by a national employer.

PMID- 9621495
TI  - Pertussis in South Australia 1893 to 1996.
AB  - This study describes trends in reports of pertussis in South Australia. Data were
      analysed from three sources: mortality data since 1893 from South Australian
      yearbooks, notification data from 1917, and hospitalisation data for pertussis or
      related complications since July 1985. Crude and age-specific rates of mortality,
      notifications and hospitalisation were compared. Pertussis peaked in 3 to 5
      yearly cycles. The mortality and notification rates have generally declined over
      time. However, since 1993 the notification rate has remained high. The median age
      for pertussis notifications increased from 4 years in 1984 to 15 years in 1996.
      Serological testing for pertussis was included in 15% of notifications in 1985
      and 90% in 1996. The age specific hospitalisation rate for pertussis was highest
      in infants < or = 6 months. Since the turn of the century, mortality and
      notification rates due to pertussis have declined. Over the past decade the major
      burden of severe disease resulting in hospitalisation has been borne by infants <
      or = 6 months. These infants are too young to be afforded protection from three
      primary immunisations against pertussis. Despite no substantial increase in
      mortality nor hospitalisation for pertussis in South Australia, the notification
      rate has remained high since 1993. This increase may be attributable to the use
      of more sensitive tests for pertussis, such as serology.

PMID- 9621496
TI  - Communicable diseases surveillance.

PMID- 9621497
TI  - [Anomalous incidence of soft tissue sarcomas in the city of Mantova].

PMID- 9621498
TI  - [The image of the professional nurse in the national health system].

PMID- 9621499
TI  - [Cause-specific mortality of asbestos-cement workers compensated for asbestosis
      in the city of Bari].
AB  - The cause-specific mortality of 233 asbestos cement workers employed by the
      Fibronit company in Bari and compensated for asbestosis was investigated. Cohort
      members were enrolled on 31.12.1979 and followed through 30.4.1997; follow-up was
      completed for 98.3% of study subjects, and causes of death were ascertained for
      96.6% of deceased subjects. Observed mortality was contrasted to that expected
      according to cause-sex-age- and calendar time-specific rates of the population
      resident in the Apulia Region. All causes observed mortality exceeded expected
      value (SMR: 117, 87 observed), due to a significant' increase in pneumoconiosis
      (SMR: 11238, 14 observed) and malignant neoplasms (SMR: 163, 38 observed)). A
      significant decrease of circulatory diseases was found (SMR: 64, 18 observed).
      Among cancer deaths, the following sites showed a significant excess: lung (SMR:
      206, 17 observed), pleura (SMR: 2551, 4 observed), mediastinum (SMR: 2367, 2
      observed) and peritoneum (SMR: 2877, 2 observed). The excess mortality due to
      asbestosis, respiratory cancer and peritoned neoplasms can be causally attributed
      to occupational asbestos exposure.

PMID- 9621500
TI  - [Occupational cancer in Italy].
AB  - The paper is a discussion of occupational cancer in Italy. The introductory
      section provides the necessary context of Italian industrialization and
      occupational health regulation. This is followed by a review of Italian
      epidemiological studies of occupational cancer risks, considered in terms of
      relative measures of risk and Attributable Risk to carcinogenic agents or
      exposure circumstances. A section attempts to establish the number of workers who
      have been exposed to carcinogens in Italy and the intensity of their exposures.
      Several cohort and case-control studies have addressed the issue of occupational
      risks, mostly among male workers. The results of these studies suggest that the
      growing incidence of and mortality by mesothelioma is explained by the widespread
      and intense exposure to asbestos in some Italian industrial settings. A high
      Attributable Risk of lung tumors among male populations in industrial areas of
      northern Italy is explained by occupational exposures. However, insufficient data
      are available for the clear definition of the extent and intensity of
      occupational exposure to carcinogenic substances. In Italy, we need to prioritize
      and maximize resources in occupational cancer epidemiology and to revitalize the
      role of national institutions. Recent legislation has established new regulations
      on the handling of carcinogenic substances in industrial settings, a new list of
      occupational diseases, and a national registry of mesothelioma linked to asbestos
      exposure. These legislative changes are expected to have positive effects.

PMID- 9621501
TI  - [Family history and risk of insulin-dependent diabetes mellitus: a population
      based case-control study].
AB  - Insulin-dependent diabetes mellitus (IDDM) is a worldwide occurrence disease of
      childhood with genetic, environmental and familial risk factors. Our study aims
      to evaluate family history as a determinant of IDDM. In a population-based case
      control study informations on all incident IDDM cases, age 0-14, diagnosed
      between January 1st 1990 and December 31st 1996 were taken from the IDDM
      population-based register of the Abruzzo Region. The control group was taken from
      the lists of children attending family paediatricians. The family history data
      collection for IDDM and non insulin-dependent diabetes (NIDDM) were obtained by a
      questionnaire, administered to parents. Risk of IDDM associated with familiarity
      in first and second degree relatives was estimated using conditional regression
      analysis. Our results show that the risk of developing IDDM is increased by
      positive family history (OR = 3.99; 95% c.i. 1.56-10.23). The risk of IDDM for
      children whose fathers or brothers are affected by IDDM is respectively 11 and 20
      times higher than for children with no family history. Family history for NIDDM
      does not influence the risk.

PMID- 9621502
TI  - [Mortality in population migrated from other Italian regions to the Tuscany
      region in 1989-94].
AB  - In the period 1989-94, mortality rates for the most important causes of death in
      people migrated to the Tuscany from other Italian regions were analysed. The area
      of birth was assessed according to the information on province of birth recorded
      on death certificates. For this analysis we classified Italy into Tuscany and
      five broad areas, each including a number of political regions: North-West, North
      East, Centre, South and Islands. The number of person-years for calculation of
      the mortality risks was based on 1991 census data, which also included
      information on place of birth and on current residence. The risks of death of
      subjects born in other Italian areas and resident in Tuscany ("migrated
      populations") in comparison to Tuscany born population were assessed by means of
      Poisson multivariate regression models. For most sites (particularly for lung and
      breast), cancer mortality rates were higher among North-West and North-East born
      people and lower among Centre, South and Islands born people. Gastric cancer
      mortality was higher in Tuscany born subjects. Cardiovascular diseases mortality
      was generally lower among people born outside of the Tuscany, with the exception
      of ischaemic heart disease (higher in North-West and Islands born people). Liver
      cirrhosis mortality was generally higher in North-West, North-East, South and
      Islands born subjects (with some differences between males and females). Diabetes
      mellitus mortality was higher in South and Islands born people. AIDS and opioids
      overdose mortality was higher in North-West born subjects. Mortality for external
      causes was higher in people born outside of the Tuscany. Both in males and
      females, overall mortality was higher in North-West and lower in South born
      people and lower in Centre and Islands born males.

PMID- 9621503
TI  - [Evaluation of migratory intraregional flow for the surgical treatment of breast
      cancer].
AB  - The migratory intraregional flows for the treatment of breast cancer have been
      analyzed in Tuscany. The analysis has been carried out taking the province of
      Pistoia as a sample and the main sanitarian Florentine structures as a pole of
      migration in the years 1992-93. The patients suffering from breast cancer were
      269 in the two years. The expected number of cases of breast cancer in the
      province is of 137.25/year. In the period considered the patients that addressed
      to Florence were 41.63% while the women remained in the province were 58.36%. The
      migration toward Florence seems to have been mainly affected by age, since most
      of the hospitalization in this pole referred to patients younger than 54. The
      sick women choose to be admitted to Florence irrespective of their residence
      municipality. The provincial hospitals in which the investigation has been
      carried out are those of Pistoia and Pescia. As far as concerns the type of
      intervention carried out in the three sanitarian poles, the surgery of
      conservative type prevails in Florence, the mastectomies in Pescia, while in
      Pistoia the two types of interventions show a comparable frequency. From such
      evidences we can assume the choice of the Florentine pole as a structure for the
      treatment of breast cancer; also in relation to the fact that in the examined
      province, in the years considered, a service of radiotherapy was not still
      active.

PMID- 9621505
TI  - [Health, epidemiology and national health system. Italian Society of
      Epidemiology].

PMID- 9621504
TI  - [Cost-effectiveness of hip fracture prevention].
AB  - We estimated the Cost Per Avoided Hip Fracture (CPAHF, millions Lira) by
      osteoporosis treatment, on the basis of a review on randomized controlled trials.
      Prevention with vitamin D3 in institutionalized elderly women is cost-neutral
      (CPAHF = -4; 95% CI = -9, +5). Prevention with alendronate in non
      institutionalized women screened on bone mineral density generates doubts (CPAHF
      = 275; 95% CI = 146, 19.426). The cost-effectiveness analyses can strengthen or
      weaken conclusions of the clinical trials and discourage the use of economically
      unsustainable preventive treatments whose efficacy is unproven.

PMID- 9621506
TI  - [Toward a national strategic research program aimed at the managerial needs of
      the Italian national health care].

PMID- 9621507
TI  - [The volume of dental training around the second millenium].
AB  - The number of Hungarian dentists around the second millennium is analysed.
      Keeping the actual number of student's intake, the number of dentists will
      decrease significantly between 2002 and 2015. Therefore, the consideration of
      this possible critical situation is urgent.

PMID- 9621508
TI  - [The use of panoramic images in daily routine nerve block analgesia].
AB  - The examination was meant to reveal if the lingula of the mandible was clearly
      recognizable and measurable on panoramic X-rays and, to what extent it was
      similar to the position of the lingula as determined by Szokoloczy's method
      applied in mandibular nerve block analgesia. Their findings were based on
      radiographs taken during daily routine, mono and dizygotic cases, and radiographs
      taken of the same patients over a period of 20 years. Further measurements were
      performed on dry mandibles, on CT pictures and on panoramic pictures taken of
      these cases. It was found that the panoramic radiographs provided information on
      cases of mandibular nerve block analgesia as well.

PMID- 9621509
TI  - [The use of benzyl alcohol and amyl-m-cresol (Strepsils) in the oral cavity.
      (Review of the literature and first clinical experiences)].
AB  - The authors summarised the literature data of benzylalcohol and amyl-m-cresol. In
      the clinical practice they used Strepsils in the treatment of 22 patients
      suffered from oral inflammatic diseases and in the 20 prophylactic cases of oral
      surgical interventions. The preliminary clinical report shows that, the Strepsils
      seems to be very effective in the treatment of oral inflammations and in the
      prophylaxis too.

PMID- 9621510
TI  - Retrotransposal integration of mobile genetic elements in human diseases.
AB  - Approximately one-third of the mammalian genome is composed of highly repeated
      DNA sequences, of which the two major families, the long and short inter-spersed
      nucleotide elements (LINEs and SINEs), are represented in humans by L1 and Alu
      elements respectively. Both 'types of element are considered to be
      retrotransposable and to play significant roles in genomic function and
      evolution. The majority of inserted elements are truncated and often rearranged
      relative to full-length elements; usually, such retrotransposed sequences are
      flanked by target-site duplications of various lengths and contain 3' polyA
      tracts, common characteristics of retrotransposal integration. Retrotransposal
      integrations of Alu and L1 sequences into biologically important genes appear to
      play significant roles in some human diseases. Most of the inserted sequences
      that cause human diseases seem to belong to one or a few subsets of each type of
      retrotransposon, suggesting that only a few active elements can function as
      templates for retrotransposition. Integrations observed in oncogenes and in tumor
      suppressor genes may participate in carcinogenesis by altering the activity of
      the affected genes. The exact mechanism of these events is unclear; however,
      retrotransposal integration may be a general mechanism of mutation in humans.

PMID- 9621511
TI  - Age-specific incidences of chromosome abnormalities at the second trimester
      amniocentesis for Japanese mothers aged 35 and older: collaborative study of 5484
      cases.
AB  - The aim of this study was to calculate the expected incidences of chromosome
      abnormalities found at amniocentesis in Japanese women aged 35 and older. From
      four clinics in Japan, we gathered genetic amniocentesis data on 5484 pregnant
      women at risk only due to their advanced age, 35 years and older. We analyzed the
      data using the logistic regression model. Of the 5484 fetuses, 117 (2.1%) were
      diagnosed with a chromosome abnormality. The abnormal karyotypes included 42
      cases of trisomy 21; 13 of trisomy 18; 7 of trisomy 13; 10 of 47,XXY; 4 of
      47,XXX; 1 of 47,XYY; 27 with various structural aberrations; and 13 with various
      types of mosaicism. The incidences of trisomy 21, lethal autosomal aneuploidies
      (trisomy 18 and trisomy 13), and sex-chromosome abnormalities (XXY, XXX, XYY)
      increased with maternal age. Parameters of the regression equations with their
      standard errors were calculated and the expected incidences of chromosome
      abnormalities at each maternal age were derived. The expected incidences of
      chromosome abnormalities obtained in this study are the first data published for
      Japan and will be useful for the counseling of pregnant women. The incidence of
      trisomy 21 is not different from the rates published previously for Western
      countries. The incidences of chromosome abnormalities are not affected by race or
      by geographic factors.

PMID- 9621512
TI  - Molecular basis of intermittent maple syrup urine disease: novel mutations in the
      E2 gene of the branched-chain alpha-keto acid dehydrogenase complex.
AB  - The E2 gene of the branched-chain alpha-keto acid dehydrogenase (BCKDH) complex
      was studied at the molecular level in three patients with intermittent maple
      syrup urine disease (MSUD). All three patients had higher BCKDH activity than did
      those with the classical phenotype. In the first patient, a single base
      substitution from A to G in intron 8 created a new 5' splice site and caused an
      insertion of 126 nucleotides between exons 8 and 9 by activating an upstream
      cryptic 3' splice site in the same intron. The predicted mRNA encoded a truncated
      protein with 282 amino acids including 4 novel ones at the carboxyl terminus,
      compared with the normal protein with 421 amino acids. In vitro, the region from
      the patient but not from a normal control was recognized and was recovered as a
      novel exon, indicating that the single substitution was responsible for
      incorporation of the region into mRNA. This mutation probably supports an exon
      definition model in which the spliceosome recognizes a 3' splice site and then
      scans downstream for an acceptable 5' splice site, thereby defining an exon. The
      second patient was homozygous for a G to T transversion at nucleotide 1463 in
      exon 11, which predicted a substitution of the termination codon by a leucine
      residue and the addition of 7 extra amino acids at the carboxyl terminus. For
      each mutation, these two patients were homozygous and their parents were
      heterozygous. The third patient was a compound heterozygote for a C to G
      transversion at nucleotide 309 in exon 4 and a G to A transition at nucleotide
      1165 in exon 9, causing an Ile-to-Met substitution at amino acid 37 and a Gly-to
      Ser substitution at amino acid 323, respectively. Taken together, these results
      indicate that the molecular basis of intermittent phenotype MSUD in some patients
      can be due to mutations in the E2 gene, giving rise to a low but significant
      residual activity of the BCKDH complex.

PMID- 9621513
TI  - Mutational analysis of the RET proto-oncogene in 71 Japanese patients with
      medullary thyroid carcinoma.
AB  - Multiple endocrine neoplasia types 2A and 2B (MEN2A and MEN2B) and familial
      medullary thyroid carcinomas (FMTC) are caused by germline mutations in the RET
      proto-oncogene. To investigate the spectrum of RET mutations among Japanese
      patients, we screened the RET gene in 71 patients with thyroid carcinomas. The
      panel included representatives of 44 families carrying FMTC or MEN2, 22 sporadic
      medullary thyroid carcinomas (MTCs), and five MTCs without familial information.
      Mutations in nucleotide sequences encoding one of three specific cysteine
      residues in the extracellular domain of the RET protein were found in 33 of the
      34 MEN2A patients and in five of the six FMTC patients examined. A mutation at
      codon 918, causing the substitution of threonine for methionine in the tyrosine
      kinase domain of the protein, was found in germline DNAs of all four patients
      with MEN2B and in two of the 22 patients with sporadic MTCs; codon 918 was
      mutated somatically in tumor DNAs from three other sporadic cases. Germline
      mutations of codon 768, GAG to GAC (Glu to Asp), were detected in one FMTC, in
      one patient with sporadic MTC, and in one of the patients without familial
      information. Two somatic mutations, an Asp to Gly substitution at codon 631 and a
      Cys to Arg substitution at codon 634, had not been reported previously. Of five
      germline mutations found among the 22 sporadic cases, four were confirmed as de
      novo mutations since in each case neither parent carried the mutation. As nearly
      one-fourth of the patients with sporadic MTCs carried germline mutations and 50%
      of their children are expected to develop MTC and other endocrine tumors, these
      results indicated the importance of careful clinical surveillance of family
      members of any patient with MTC.

PMID- 9621514
TI  - Mutations in the hepatocyte nuclear factor-1 alpha gene (MODY3) are not a major
      cause of early-onset non-insulin-dependent (type 2) diabetes mellitus in
      Japanese.
AB  - Maturity-onset diabetes of the young (MODY3), a monogenic subtype of non-insulin
      dependent diabetes mellitus (NIDDM) with an early age of onset, is characterized
      by a primary defect in insulin secretion. Recently, it has been shown that
      mutations of the gene encoding the transcription factor hepatocyte nuclear factor
      1 alpha (HNF-1 alpha) cause MODY3. Since NIDDM in Japanese is characterized by
      insulin secretory defects due to primary beta-cell dysfunction, we screened 60
      Japanese nonobese subjects with early-onset NIDDM for mutations in this gene, 45
      of whom had a first-degree relative with NIDDM. Direct sequencing of the ten
      exons and flanking introns of the gene in these subjects identified eight
      nucleotide substitutions including two amino acid changes, Ile-27-Leu and Ser-487
      Asn, the frequencies of which were not significantly different in subjects with
      early-onset NIDDM and nondiabetic subjects. These results suggest that mutations
      in the HNF-1 alpha gene are not a major cause of early-onset NIDDM in Japanese.

PMID- 9621515
TI  - Analysis of bilirubin uridine 5'-diphosphate (UDP)-glucuronosyltransferase gene
      mutations in seven patients with Crigler-Najjar syndrome type II.
AB  - Crigler-Najjar syndrome (CN) type II is caused by a reduction in hepatic
      bilirubin uridine 5'-diphosphate (UDP)-glucuronosyltransferase activity.
      Recently, there has been progress in mutation analysis of patients with CN type
      II. Here, we analyzed both the coding and the promoter regions of the gene in
      seven Japanese patients with CN type II from five unrelated families. The
      mutations found in this study were classified into three types. The first type
      was composed of double homozygous missense mutations (Gly71Arg and Tyr486Asp) in
      exons 1 and 5. These mutations, which were detected in five patients from three
      unrelated families, were the commonest. The second type, which was detected in
      one patient, consisted of a single homozygous missense mutation (Arg209Trp) in
      exon 1. The third type, which was detected in one patient and was a new type of
      mutation combination, was composed of a homozygous insertion mutation of the
      TATAA element and a heterozygous missense mutation (Pro229Gln) in exon 1.
      Although the first and the second type of mutations are recessive, the third type
      appears to be dominant with incomplete penetrance, since the allele frequency of
      the insertion mutation of the TATAA element is very high (40%).

PMID- 9621516
TI  - Cloning and chromosomal mapping of a novel ABC transporter gene (hABC7), a
      candidate for X-linked sideroblastic anemia with spinocerebellar ataxia.
AB  - We isolated a novel human ATP-binding cassette (ABC) transporter cDNA, determined
      its nucleotide sequence, and designated it human ABC7 (hABC7). The nucleotide
      sequence was highly homologous to the ATM1 gene in yeast, which encodes an ABC
      transporter (yAtm1p) located in the mitochondrial inner membrane. The deduced
      human product, a putative half-type transporter, consists of 752 amino acids that
      are 48.9% identical to those of yAtm1p. A computer-assisted protein structural
      and localization analysis revealed that the mitochondrial targeting signal of
      yAtm1p is conserved in the N-terminal region of the primary sequence of the hABC7
      protein, and therefore this product is also likely to be located in the
      mitochondrial inner membrane. The evidence strongly suggests that the hABC7 gene
      is a counterpart of ATM1 and that its product is probably involved in heme
      transport. We mapped the hABC7 gene to chromosome Xq13.1-q13.3 by fluorescence in
      situ hybridization. As band Xq13 has been implicated in X-linked sideroblastic
      anemia with spinocerebellar ataxia, hABC7 becomes a candidate gene for this
      heritable disorder.

PMID- 9621517
TI  - Identification of brain-specific splicing variants of the hDLG1 gene and altered
      splicing in neuroblastoma cell lines.
AB  - The human homologue of Drosophila tumor suppressor dlg, hDLG1, is one of the
      proteins known to interact with APC, a tumor suppressor for colorectal cancer.
      Alternative splicing of this gene generates transcripts either with [insertion 1
      (I1)] or without 99 nucleotides in the 5' part of the dlg homology repeats (DHR)
      domain. We found almost equivalent expression of these two splicing variants in
      most human tissues; however, in skeletal muscle the transcript with the 99-bp
      insertion was predominant, and in the brain, that without the 99-bp insertion was
      expressed predominantly. We also examined alternative splicing in the region
      between the SH3 and GUK domains where two different sizes of insertions, 34
      nucleotides (I2) or 100 nucleotides (I3), had been reported, and found various
      splicing patterns among the tissues examined. In brain we detected six different,
      alternatively spliced transcripts, two of which included a novel, 36-bp, brain
      specific exon encoding a peptide bearing significant homology to a portion of rat
      synapse-associated protein, SAP97/PSD95. Subsequently, we investigated the
      splicing patterns of the hDLG1 gene in 24 neuroblastoma cell lines. In two-thirds
      of these lines, the splicing patterns were altered from those observed in normal
      brain tissue. As one-third retained the normal brain-splicing pattern, the loss
      of normal splicing of hDLG1 may not in itself cause formation of tumors, but it
      might reflect the biological character of individual neuroblastomas.

PMID- 9621518
TI  - Mutation and polymorphic marker analyses of 65K- and 67K-glutamate decarboxylase
      genes in two families with pyridoxine-dependent epilepsy.
AB  - Pyridoxine-dependent epilepsy is a disease inherited as an autosomal recessive
      trait, characterized by rapid response to pharmacological dosages of pyridoxine.
      The defect has been suggested to reside in glutamate decarboxylase (GAD), since a
      mutant GAD with an abnormally high Km for a cofactor, pyridoxal phosphate, could
      not synthesize an adequate amount of gamma-amino butyric acid [Scriver and Whelan
      (1969) Ann NY Acad Sci 166: 83]. To test this hypothesis, we studied two affected
      families by screening for mutations in the GAD mRNA and by analyzing a
      polymorphic marker in the GAD gene. Since two forms of GAD, GAD65 and GAD67, have
      been identified in human brain, we analyzed both forms. To overcome the limited
      accessibility of brain tissues, we utilized the minute amounts of GAD mRNAs
      ectopically transcribed in lymphoblasts. The ectopic GAD transcripts were
      amplified by reverse-transcription-mediated, nested polymerase chain reaction for
      mutation analysis. Two and three base substitutions were found in GAD65 and GAD67
      cDNAs, respectively. All of them were, however, polymorphisms that were also
      found in control subjects. We then examined a (CA) repeat polymorphism in the
      GAD65 gene and found that different maternal alleles were transmitted to two
      affected sibs in one family. Thus, an etiological mechanism other than a K(m)
      mutant GAD is responsible for pyridoxine-dependent epilepsy.

PMID- 9621519
TI  - Genomic organization and mapping of the human activin receptor type IIB (hActR
      IIB) gene.
AB  - Activins, members of a family of proteins that includes transforming growth
      factor-beta (TGF-beta), are gonadal polypeptide hormones that stimulate secretion
      of follicle-stimulating hormone (FSH). During large-scale sequencing analysis of
      a 1.2-Mb fragment of human genomic DNA on 3p22-p21.3, we found the gene encoding
      activin receptor type IIB (hActR-IIB). Comparison of its reported cDNA sequence
      with this genomic sequence showed that the hActR-IIB gene consists of 11 exons
      and spans about 30 kb of genomic DNA.

PMID- 9621520
TI  - A one-base deletion (183delC) and a missense mutation (D276H) in the T-protein
      gene from a Japanese family with nonketotic hyperglycinemia.
AB  - Two novel mutations in the gene encoding T-protein, a component of the glycine
      cleavage system, were identified in a Japanese family with nonketotic
      hyperglycinemia. The proband had two affected sibs, and enzymatic analysis of the
      liver sample from the proband revealed the T-protein deficiency. The first
      mutation, 183delC, was found in exon 1. One of six cytidine residues (base
      position 183-188) was deleted. The deletion was located in a coding region of the
      mitochondrial leader peptide and was deduced to create a truncated peptide with
      94 amino acids. The second mutation was a base substitution from G to C at
      position 955 in exon 7. The G955C substitution caused an amino acid change from
      aspartate to histidine at position 276 (D276H). Aspartic acid at position 276 is
      evolutionarily conserved among human, bovine, chicken, and pea genes, and
      replaced by glutamic acid in Escherichia coli, suggesting that the presence of an
      acidic amino acid at 276 may be crucial for the enzymatic function. No base
      change other than the 183delC and the G955C was observed in the sequencing
      analysis. Familial analysis revealed that the 183delC and the D276H mutations
      were inherited from the father and the mother, respectively. This is the first
      report of T-protein gene mutation in Oriental patients with nonketotic
      hyperglycinemia.

PMID- 9621521
TI  - Maternal uniparental disomy for chromosome 14 in a boy with intrauterine growth
      retardation.
AB  - Maternal uniparental disomy (UPD) for chromosome 14 [upd(14)mat] may cause a
      characteristic phenotype with growth and developmental deficiency and precocious
      puberty. We report the case of a Japanese infant with an isochromosome 14
      [i(14q)] and intrauterine growth retardation (IUGR). The infant is one of
      triplets comprising a boy (the patient) and two karyotypically normal girls. We
      analyzed parent-child transmission modes of alleles on the i(14q) at 17 CA-repeat
      marker loci along the entire length of chromosome 14. Genotypes at 4 proximal and
      5 distal loci on the i(14q) were consistent with maternal isodisomy, whereas
      those at an intervening region indicated maternal heterodisomy. Thus, the
      derivative chromosome 14 had arisen through a translocation between maternal
      homologous chromosomes 14 [t(14;14)(p10;q10)] after at least two crossing-over
      events at the first meiosis. This result also suggests that there must be
      maternally imprinted gene(s) on 14q, and that loss of the functionally active,
      paternally derived allele in the same locus may lead to IUGR. Alternatively, IUGR
      may be an autosomal recessive trait. In the latter case, the mother would be a
      heterozygote and the putative disease locus would be either at the most proximal
      or most distal region of 14q.

PMID- 9621522
TI  - Novel germline mutations of hMSH2 in a patient with hereditary nonpolyposis
      colorectal cancer (HNPCC) and in a patient with six primary cancers.
AB  - We screened for germline mutations of mismatch repair genes, hMLH1 and hMSH2, in
      five Japanese families carrying hereditary nonpolyposis colorectal cancer (HNPCC)
      and in a patient with multiple primary cancers. Screening the entire coding
      regions of both genes using polymerase chain reaction-single strand conformation
      polymorphism (PCR-SSCP) analysis, we found two novel germline mutations in hMSH2.
      One was a 1-bp insertion in exon 12, detected in a patient who had undergone
      surgery six times for independent tumors (four primary colorectal carcinomas, a
      small intestinal carcinoma, and an endometrial cancer). The other, in a second
      patient, was a missense mutation from CTT to TTT at codon 390 in exon 7 that
      resulted in substitution of phenylalanine for leucine. This conservative
      alteration was not found in any of 50 normal controls, but we cannot exclude the
      possibility that it may represent a rare polymorphism rather than a factor in the
      disease.

PMID- 9621523
TI  - A polymorphic CA repeat sequence at the human calcitonin locus.
AB  - A polymorphic dinucleotide (CA) repeat sequence was isolated from a genomic clone
      containing the human calcitonin gene at 11p15.2-p15.1. This polymorphism will be
      a useful marker in the genetic study of disorders affecting calcium metabolism
      including hyperparathyroidism, hypoparathyroidism, and osteoporosis.

PMID- 9621524
TI  - Sickle cell disease and the general surgeon.
AB  - Sickle cell disease (SCD) is a common genetic disorder which represents a major
      medical problem in certain parts of the world. It is characterized by chronic
      haemolytic anaemia and vaso-occlusive crises, which can lead to widespread
      vascular occlusion by sickled red blood cells leading to multiple organ
      infarctions. In this respect, SCD can be considered as a multisystem disease
      presenting, to various surgical disciplines, a wide variety of surgical ailments.
      As surgical management of these patients is associated with high morbidity and
      mortality, close collaboration between medical and surgical services is
      essential. Greater population mobility makes recognition of the surgical
      implications of this disease of paramount importance in surgical practice. This
      article reviews surgical problems with which SCD patients may present to general
      surgeons and discusses their management.

PMID- 9621525
TI  - Systemic or regional chemotherapy: does it matter and should surgeons be
      involved?
AB  - TNF (tumour necrosis factor) is a new immunological anti-cancer agent which is
      too toxic for systemic use and relatively ineffective when used alone, but
      remarkably effective when used in closed circuit perfusion techniques together
      with other anti-cancer agents. Several studies have shown that when TNF is used
      with melphalan in closed circuit perfusion treatment for multiple melanoma
      metastases confined to a limb, a response rate of 80% can be achieved compared to
      a best response rate of 40% with melphalan alone. These findings confirm the
      difference in tumour responses which can be achieved with the appropriate use of
      regional chemotherapy in treatment of locally advanced tumours and the importance
      of surgical oncologists and vascular radiologists in maintaining and developing
      skills in integrated regional cancer treatment.

PMID- 9621526
TI  - Prospective randomized controlled trial comparing Lichtenstein with modified
      Bassini repair of inguinal hernia.
AB  - We present a prospective randomized study of 80 patients with inguinal hernia who
      underwent either a modified Bassini repair (n = 38) or a Lichtenstein mesh repair
      (n = 42). Treatment groups were matched for age, side of hernia, type of hernia
      and ASA grade. There was no difference in the time taken to perform the two
      operations: the mean time taken to perform Lichtenstein repair was 26.8 min
      (range 12 to 49), Bassini repair taking a mean of 27.5 min (range 9 to 51), P =
      0.76. There was, however, a difference between the operating times with respect
      to the type of hernia present, direct hernias being the fastest to repair. Pain
      scores were assessed by a visual analogue scale, and there was significantly less
      pain in the Lichtenstein group, P = 0.028. Despite this, there was no difference
      between the analgesic requirements of the two groups, P = 0.073. In order to
      assess rehabilitation, lengths of time not working and not driving were assessed.
      There was no difference in either measurement, P = 0.335 and 0.467 respectively.
      Patients were followed up a mean of 7 weeks post-operatively (range 1 to 13
      weeks). There was no significant difference between the two procedures with
      regard to post-operative urinary complications, wound infection or other
      complications. All measurements except the time taken to perform the operation
      were independent of the surgeon involved. The accuracy of the clinical diagnosis
      was also assessed, and found to be moderate, with 63% of diagnoses being correct.

PMID- 9621527
TI  - A grading system in day surgery: effective utilization of theatre time.
AB  - An in-house audit revealed a theatre utilization time in the day surgery unit of
      70%. The reason identified for this poor theatre utilization was patient
      selection by the clerical staff based on a fixed number of cases per session. A
      grading system which estimated the anticipated duration of operation time was
      introduced as the basis for patient selection in the day surgery. A pilot study
      of 20 patients revealed that the system was both effective and simple to
      implement. It was therefore adopted. A re-audit of a further 299 patients treated
      using the grading system revealed that theatre utilization time had increased
      from 70 to 98%. The number of patients treated per session also increased, thus
      effectively reducing the waiting list. The grading system can be used in all
      clinical specialities providing day case surgery and we recommend it.

PMID- 9621528
TI  - Gynaecomastia: have Webster's lessons been ignored?
AB  - Five cases of cosmetically unacceptable and hypertrophic scarring are presented
      that follow excision of gynaecomastia by surgeons who used incisions other than
      the periareolar approach. A periareolar technique of subcutaneous mastectomy is
      described and recommended.

PMID- 9621529
TI  - Screening for diabetes in lower limb amputees: a pilot study.
AB  - The Saint Vincent Declaration includes 5-year targets to improve the outcome of
      diabetic patients as a central tenet. Meeting these targets requires a
      comprehensive screening and monitoring programme to establish the current
      incidence of diabetic complications and show that the major goals of the
      declaration are being achieved. The Scottish Physiotherapy Amputee Research Group
      and the Scottish Vascular Audit Group jointly organized a three month prospective
      screening programme of 146 patients presenting for a lower limb amputation. The
      results suggest that a significant proportion of patients have undiagnosed
      diabetes. Further, only around half of the patients eligible for testing actually
      had a test done, highlighting the difficulties associated with establishing a
      national screening programme. This programme is now ongoing and particular
      importance is being given to improving the proportion of patients actually being
      tested.

PMID- 9621530
TI  - Out-patient follow-up after total hip replacement in one health region.
AB  - A postal survey was carried out of all orthopaedic surgeons in the West Yorkshire
      Health region enquiring about out-patient follow-up practices after total hip
      replacement. Follow-up is advised to detect problems that can more effectively be
      resolved if detected early. A huge variation in the number, timing and nature of
      appointments following discharge was demonstrated. The total length of follow-up
      varied between 3 months and indefinite follow-up. The number of visits in the
      first post-operative year varied between one and four. The considerable variation
      in post surgery follow-up of these patients has important cost implications. Some
      patients will have unnecessary appointments whereas others will be inadequately
      reviewed. Guidance is required on the appropriate review of these patients which
      will allow early detection of joint failure in a way that is efficient in terms
      of the time and cost of out-patient follow-up.

PMID- 9621531
TI  - Simple repair of fractured penis.
AB  - Though rare, fracture of the penis is associated with significant morbidity if
      early surgical repair is not carried out. A simple same-day surgical technique
      performed under local anaesthesia is presented that requires no pre-operative
      investigations. Careful clinical examination (rolling sign) is used to accurately
      identify the fracture site.

PMID- 9621532
TI  - Adult tonsillectomy: what proportion would accept same day discharge?
AB  - Day case surgery is increasing to improve health care cost efficiency. The
      economic benefits of day surgery depend on how many patients accept same day
      discharge. This study aims to investigate what proportion of adults undergoing
      tonsillectomy would accept same day discharge and reasons for refusal. Fifty
      consecutive adults undergoing in-patient tonsillectomy who satisfied criteria for
      day surgery were prospectively studied. All patients had the same day case;
      anaesthetic, tonsillectomy technique, analgesia and antiemetic. Eight hours after
      surgery patients were given discharge information and asked whether they would
      accept discharge. Those patients who refused discharge were asked to specify why.
      Additional morphine requirements were noted. Fifty-two percent of patients would
      accept same day discharge. Reasons for refusal were; pain 46%, nausea 33%,
      dizziness 13% and pain and nausea 8%. Those refusing discharge were three times
      more likely to have received additional morphine. These results compare
      unfavourably with oversees studies and this may be due to sampling bias. Further
      studies are required.

PMID- 9621533
TI  - Perforation rate relates to delayed presentation in childhood acute appendicitis.
AB  - To determine if perforation rate is a function of delayed diagnosis or delayed
      presentation in childhood acute appendicitis we performed a retrospective
      casenote review of 101 consecutive children undergoing emergency appendicectomy
      over a 12-month period. The perforation rate was 7% in those children presenting
      with symptoms of 1 day or less and was significantly greater (33%, Chi 2 = 9.45,
      P < 0.01) in those who had had symptoms for more than 1 day at presentation.
      There was no difference in in-hospital delay between the groups. A high
      perforation rate was found to be a feature of delayed presentation.

PMID- 9621534
TI  - Achalasia cardia in infancy and childhood: an Indian experience.
AB  - Seven children with achalasia cardia, six of them infants, were seen over a 10
      year period. In infantile achalasia, respiratory symptoms predominate and
      vomiting may easily be mistaken for gastroesophageal reflux (GER). Vomiting of
      uncurdled milk is characteristic of achalasia. Six children underwent
      esophagocardiomyotomy with good results in five. The procedure was transthoracic
      in two and transabdominal combined with an anterior fundoplication in the others.
      There was one post-operative death. Achalasia and alacrima were associated in two
      infants. One baby with this association also had a neurogenic bladder.

PMID- 9621535
TI  - Indications for third molar surgery.
AB  - Recent reports have suggested that the practice of prophylactic lower third molar
      surgery is widespread, possibly account for up to 50% of all patients treated. An
      objective effort to refute the findings of the previously published data was
      undertaken by the Maxillofacial Unit of a large district general hospital trust.
      A prospective study of 454 consecutive patients referred for third molar surgery
      demonstrated that in 96% of the patients, at least one nationally defined
      criteria for surgery was present. A concurrent retrospective audit of patients
      already on the waiting list for surgery identified that 97% had at least one
      valid criterion for surgery. Of those patients who presented with unilateral
      symptoms, over half had only the troublesome side removed. Only 11 out of 454
      patients were accepted for treatment without a defined criterion, all of whom had
      partially erupted teeth. The evidence presented in the current study is compared
      with previously reported data and possible reasons for the variance are
      discussed.

PMID- 9621536
TI  - Laparoscopic removal of a foreign body from the intestine.
AB  - Foreign bodies are often introduced into the gastrointestinal tract of both
      adults and children. At times this is intentional and at others it is accidental.
      The doctor is usually faced with the problem of deciding whether to apply
      expectant treatment, endoscopy or surgery to obtain an optimum outcome. The
      management depends on the type of object, the organ affected, the type of
      symptoms and the condition of the patient in deciding if, when and how to
      intervene. A case is reported here where a method not previously described was
      used to retrieve a sewing needle from the distal ileum.

PMID- 9621537
TI  - The use of laparoscopy in a case of appendiceal cystadenoma presenting as
      pseudomyxoma peritonei in an inguinal hernial sac.
AB  - A case is reported of a patient with a benign appendiceal neoplasm presenting
      incidentally with mucin in an inguinal hernial sac. Only one such case of a
      benign tumour, and one such case of cystadenocarcinoma, have previously been
      reported. In neither of these cases was laparoscopy used in diagnosis or staging
      of the disease. We review the management of such cases in light of recent
      proposed changes to pathological classification.

PMID- 9621538
TI  - Perforation of the heart by a swallowed open safety-pin in an infant.

PMID- 9621539
TI  - Unrecognized osteochondral radial head fracture causing elbow locking.

PMID- 9621540
TI  - Meningeal carcinomatosis: an unusual cause of deafness.
AB  - Meningeal carcinomatosis is the diffuse infiltration of the meninges by
      metastatic carcinoma. Patients usually have a known underlying malignancy, but
      primary presentation can be with symptoms of meningeal involvement. The cases are
      reported of two patients who presented with sensorineural hearing loss. The roles
      of gadolinium-enhanced magnetic resonance imaging and cerebrospinal fluid
      cytology in reaching the diagnosis are discussed.

PMID- 9621541
TI  - Base of skull internal carotid and internal jugular gunshot wounds treated
      conservatively: inadequate treatment, or was well enough left alone?
AB  - Zone three carotid injuries present problems of access in emergency situations.
      Not only are the methods time consuming, but they also put certain structures in
      the neck at risk. A patient was treated at this institution with a large calibre
      gunshot injury of the right internal carotid and internal jugular vein. He was
      neurologically intact and his bleeding had been completely controlled. A decision
      was made to treat him conservatively and he recovered uneventfully with no
      neurological deficit and no further bleeding. Emergency exposure of the distal
      carotid artery involves dislocating the mandible, putting the facial nerve and
      parotid gland at risk of injury. Base of skull carotid injuries are best treated
      expectantly if there is no active bleeding or progressive neurological
      impairment. Careful follow-up is required to diagnose and treat carotid-jugular
      fistulas, false aneurysms and stenoses early.

PMID- 9621542
TI  - Recurrent left cervical abscess secondary to persistent pyriform sinus fistula.
AB  - Congenital pyriform sinus fistula is a rare defect arising from the failure of
      obliteration of the third or fourth pharyngeal pouch remnant. It is a recognized
      potential cause of acute suppurative thyroiditis.

PMID- 9621543
TI  - The investigation of symptomatic inguinal hernia: a complication of barium enema.

PMID- 9621544
TI  - Performance indicators in surgery.

PMID- 9621545
TI  - Hand problems presenting to a district general hospital accident and emergency
      department.

PMID- 9621546
TI  - Hand problems presenting to a district general hospital accident and emergency
      department.

PMID- 9621547
TI  - Hand problems presenting to a district general hospital accident and emergency
      department.

PMID- 9621548
TI  - Parathyroidectomy in chronic renal failure; comparison of three operative
      strategies.

PMID- 9621549
TI  - The use of CO2 laser for airway maintenance in obstructive supraglottic
      carcinoma.

PMID- 9621550
TI  - A safer alternative to the spirit lamp as a mirror warmer in otolaryngology.

PMID- 9621551
TI  - Surgeon protection: early recognition of glove perforation using a green under
      glove.

PMID- 9621552
TI  - Calcium alginate as haemostatic swabs in hip fracture surgery.

PMID- 9621554
TI  - Emergency abdominal surgery in the elderly.

PMID- 9621555
TI  - Vascular complications following intravascular self-injection of addictive drugs.

PMID- 9621556
TI  - Non-cytotoxic control of colorectal cancer.

PMID- 9621557
TI  - Direct listing for tonsillectomy.

PMID- 9621558
TI  - Just a 'wee prick' with a needle.

PMID- 9621559
TI  - [Incidence of antibodies in raccoon dogs and deer inhabiting suburban areas].
AB  - We evaluated the incidence of antibodies against canine distemper (CD) virus,
      canine parvovirus, Toxoplasma gondii (T. gondii), Aujeszky's disease virus,
      porcine reproductive and respiratory syndrome virus, Rickettsia tsutsugamushi,
      Rickettsia japonica, and Coxiella burnetii in 30 raccoon dogs and 5 deer captured
      in suburban areas in Kanagawa Prefecture. Among the raccoon dogs, anti-T. gondii
      antibody was detected in 1 animal (3.3%) and anti-CD virus antibody in 9 (30.0%).
      However, antibodies against the other pathogenic microorganisms were not detected
      in the raccoon dogs. The deer had none of the examined antibodies.

PMID- 9621561
TI  - [Pathological changes by the imbalance of host T helper lymphocyte subsets in
      Mycoplasma pulmonis pneumonia of mice].
AB  - To evaluate the contribution of the subsets of T helper lymphocyte (Th) to the
      development of pulmonary lesion in mycoplasma pneumonia, we compared the
      pathological findings between Th1 dominant mice (C57BL/6) and Th2 dominant mice
      (BALB/c) in experimental Mycoplasma pulmonis (M. pulmonis) pneumonia. Mice (ICR,
      C57BL/6, and BALB/c) were intranasally inoculated with 0.03 ml of a solution
      containing M. pulmonis (1 x 10(8)) colony forming units per ml. Another M.
      pulmonis inoculated ICR mice were treated with interleukin-2 (IL2; 4.8
      micrograms/day), days 3-9, intracutaneously). All mice were sacrificed at day 14,
      and the lung specimens were examined. Peribronchial lymphocyte cuffing was more
      prominent in C57BL/6 mice than that of ICR mice, and intra-alveolar inflammatory
      cell infiltration in BALB/c mice was more prominent than in ICR mice.
      Pathological patterns of the lung in IL-2 treated ICR mice were mimicking those
      of C57BL/6 mice. These results suggested that pathological patterns of mycoplasma
      pneumonia in mice might be altered by the imbalance of host T helper lymphocyte
      subset.

PMID- 9621560
TI  - [Sensitivity of Helicobacter pylori to amoxicillin and clarythromycin with
      special reference to eradication therapy].
AB  - We isolated strains of Helicobacter pylori from gastric mucosa of patients with
      peptic ulcer before and after eradication therapy, and studied their sensitivity
      to amoxicillin (AMPC) and clarythromycin (CAM). Of 85 strains of H. pylori
      isolated before therapy, MIC90 was 0.025 microgram/ml and no strains were
      resistant to AMPC. On the other hand, MIC90 of CAM was 0.05 microgram/ml and
      seven (8.2%) were already resistant to CAM. The H. pylori strains from eight
      cases of failed eradication therapy with lansoprazole + AMPC remained AMPC
      sensitive. However H. pylori strains from nineteen cases (82.6%) out of 23 of
      failed eradication therapy with lansoprazole + CAM became CAM resistant. The
      situation was similar for the cases of failed eradication therapy with
      lansoprazole + AMPC + CAM. Drug sensitivity tests prior to eradication therapy
      are to be recommended. A disc method may be used as a simple alternative to MIC
      measurement.

PMID- 9621562
TI  - [Use of Caco-2 cells for isolation of influenza virus].
AB  - In this study we assessed the usefulness of Caco-2 cells, derived from a human
      colon carcinoma, to isolate an influenza virus. Throat washings collected from 30
      patients with influenza-like illnesses in Miyazaki Prefecture in 1997 were
      inoculated in MDCK and Caco-2 cells, 17 influenza virus strains were isolated in
      MDCK cells, and 20 in Caco-2 cells. Of all the viruses isolated, only one strain
      was identified as influenza virus type B; other strains were identified as type A
      (H3N2). Furthermore, some influenza viruses were isolated in Caco-2 cells also
      from the specimens collected between 1991 and 1997. With Caco-2 cells, each type
      of influenza virus was isolated effectively without the supplement of trypsin in
      the culture medium. These facts indicate the usefulness of Caco-2 cells as a host
      to isolate influenza virus as shown to be suitable in the detection of many types
      of enteric viruses. Caco-2 cells will serve as a useful cell line for the
      surveillance of infectious disease because Caco-2 cells are sensitive to a wide
      range of virus.

PMID- 9621563
TI  - [A clinical study of pulmonary cryptococcosis. The Study Group of Respiratory
      Mycosis in Kyoto].
AB  - During the 7 years from 1990, thirty-two patients (20 in male and 12 in female,
      mean age; 53 years old) were diagnosed as having pulmonary cryptococcosis. To
      clarify the essential points for early diagnosis of pulmonary cryptococcosis, we
      reviewed the clinical records and chest images. Three patients had a past history
      of pulmonary tuberculosis and eleven patients had underlying disorders such as
      malignancy, chronic pulmonary diseases and so on, but no HIV infection, which
      would affect this disease. Eighteen patients did not have any past history nor
      complications. The symptoms such as cough, sputum, chest pain and fever were
      generally of low-grade, 14 patients had no symptom at diagnosis. Except of some
      patients with severe infections and severe underlying disorders, laboratory
      findings such as inflamatory and nutritious markers were almost within near the
      normal range. On plain chest X-ray films the distribution of lesions was almost
      in proprtion to the volume of the lobes. The multifocal nudular and/or
      infitrative shadows wer observed in about 2/3 cases and single lesion in about
      1/3. The width of lesions were minimal except of one case with interstitial
      pneumonia and two cases with multifocal segmental pneumonia. The cavity lesions
      were observed in 7 cases and hilar lymphadenopathy in 3 cases. On CT images, the
      lesions were almost located in the outer zone, the lesions which were adjacent to
      the pleura were observed in 15 cases. Cavitary lesions were almost smooth in edge
      and ubiquitous, the walls were also thick. The peripheral air-bronchogram in the
      nodular/infitrative shadows were observed in three cases. Pulmonary
      cryptococcosis is air-borne and almost a chronic infection except in AIDS
      patients, so careful planning for examination is essential with considerations of
      the characteristics of clinical and imaging features of this infection.

PMID- 9621564
TI  - [Antibody response of inactivated influenza vaccine in the elderly].
AB  - The antibody responses of 31 elderly persons (11 males and 20 females, mean 82.2
      years) and 23 adults (mean 40.7 years) to inactivated influenza vaccine were
      studied. Participants were given twice the influenza vaccine containing
      A/Yamagata/32/89, A/Kitakyusyu/159/93, and B/ Mie/1/93. Serum specimens were
      obtained before vaccination, and 2 weeks and 3 months after the second
      vaccination. Antibody to influenza was determined by hemagglutination inhibition
      test (HI). The rates of fourfold or greater increases of HI antibody against the
      A/Yamagata, A/ Kitakyusyu, and B/Mie were 96.8%, 100%, and 74.2%, and there was
      no significant difference of the rates of fourfold or greater increases between
      elderly persons and adults. The rates of possession of HI antibody more than 128
      in titer after vaccination were significantly higher than those of HI antibody
      before vaccination, and were maintained at high levels up to three months after
      the second vaccination. These results suggest that antibody response to the
      inactivated influenza vaccine is satisfactory in the elderly.

PMID- 9621565
TI  - [Mechanism of resistance of Shigella flexneri 2a resistant to new quinolone
      antibiotics].
AB  - A Shigella flexneri 2a strain, which did not respond clinically or in laboratory
      tests to treatment with new quinolone derivatives, was isolated for the first
      time in Japan from a patient admitted for diarrhea to a Tokyo hospital. The
      mechanism of resistance was examined by sequencing the quinolone resistance
      determining region (QRDR) of the gyrA (a quinolone target enzyme) gene and by
      comparing the active efflux mechanisms of two strains isolated from this patient
      (before hospitalization and after tosufloxacin treatment) and one strain isolated
      from a patient with secondary infection with that of the standard strain ATCC
      29903. DNA sequencing revealed that two amino acid substitutions, namely, Ser
      (TCG)-83-->Leu (TTG) and Asp (GAC)-87-->Gly (GGC), had occurred in the gyrA of
      all 3 strains isolated from the patients. Examination of the accumulation of
      antibiotics in these 3 strains revealed that the strain isolated after
      tosufloxacin treatment had the highest resistance to tosufloxacin, and exhibited
      decreased accumulation of tosufloxacin in the bacterial cells discharged after 5
      days of treatment with this antibiotic. However, accumulation was restored by
      addition of a proton-pump inhibitor. These results suggest that the strains
      isolated from the inpatient and the patient with secondary infection acquired
      resistance due to dual gyrA mutation induced by treatment with new quinolone
      antibiotics. Furthermore, in addition to this dual mutation, the active efflux
      mechanism also appears to be associated with resistance in bacteria that have
      been exposed to tosufloxacin.

PMID- 9621566
TI  - [Therapeutic effect of cefluprenam on polymicrobial urinary tract infection
      associated with Enterococcus faecalis, using the infectious urolithiasis model in
      rats].
AB  - We examined the therapeutic effect of cefluprenam (CFLP) on the polymicrobial
      urinary tract infection associated with infectious stones as compared to that of
      ceftazidime (CAZ), using the experimental polymicrobial urinary tract infection
      caused by Proteus mirabilis (P. mirabilis), Pseudomonas aeruginosa (P.
      aeruginosa) and Enterococcus faecalis (E. faecalis). In order to form bladder
      stones in rats, a sterile zinc ring was implanted as a foreign body, followed by
      inoculating P. mirabilis E05106 transurethrelly. Thereafter, P. aeruginosa
      E030033 and E. faecalis 966 were inoculated according to the same way. CFLP or
      CAZ was administered intravenously twice a day for 5 days. The therapeutic effect
      was evaluated by the eradication of these bacteria from the urine, the kidney and
      stones, inhibition of growth of stones, and also a value of BUN. The urinary
      excretion rates of CFLP and CAZ was also determined (20 mg/kg). In result, CFLP
      significantly more effective in the eradication of P. mirabilitis, P. aeruginosa
      and E. faecalis from the urine, the kidney and stones than the control than the
      control (p < 0.05). Furthermore, CFLP significantly more effective in the
      eradication of P. aeruginosa from the urine and also E. facalis from the urine
      and stones (p < 0.05). Meanwhile, CAZ significantly more effective in the
      eradication of P. mirabilis from the urine, the kidney and stones and also P.
      aeraginosa from the kidney and stones than the control. However, CAZ did not show
      eradicative effect on E. faecalis. The urinary excretion rates of CFLP and CAZ at
      rats were 59.3% and 59.4%, respectively, within 8 hrs after administration,
      showing a similar excretion pattern. CFLP exhibited the prominent therapeutic
      effect on polymicrobial urinary tract infection associated with infectious stones
      caused by P. mirabilis, P. aeruginosa and E. faecalls. On the basis of these
      results, it has been strongly suggested that CFLP is highly beneficial in the
      management of intractable polymicrobial urinary tract infectious in clinic.

PMID- 9621567
TI  - [Study on the role of mucoid strain in chronic airway infections].
AB  - This study was investigated to eludiate the clinical role of immune complexes
      (IC) formed by alginate of persistently colonized mucoid strain in chronic airway
      infection. 1. Clinical Observation Twenty-four cases colonized with mucoid strain
      and 16 cases with non-mucoid strain were enrolled. Their serum indexes to anti
      alginate specific IgG subclass antibodies and level of IC were determined by
      enzyme linked immunosorbent assays. Significantly higher level of the IgG1, IgG3
      and higher level of IC were observed in the group of mucoid positive cases.
      Deposition of IgG1, IgG3, and IC on the affected part of interstitial lung tissue
      in a case of persistent infection with mucoid Pseudomonas aeruginosa was
      detected. 2. Experimental Observation Ninety mice immunized with alginate were
      used. They were intubated with 20 micrograms/body of alginate, 4 x 10(6) colony
      forming unit/body of mucoid Pseudomonas aeruginosa: PT1252, or 40
      microliters/body of IC into each group. Then after Fc gamma receptor (Fc gamma R)
      on neutrophils in bronchoalveolar lavage fluid was analyzed by flow cytometric
      technique. Expression of Fc gamma R on neutrophils was inhibited against alginate
      intubation and IC one. In contrast, Fc gamma R expression was increased at
      initial phase after mucoid Pseudomonas aeruginosa intubation, which was
      influenced by nonspecific activation of neutrophils due to bacterial infection.
      3. Conclusive Words From the above, The expression of Fc gamma R on neutrophils
      was inhibited by alginate. It may be that IC deposition on lung tissue in chronic
      airway infection with mucoid strain was persisted by poor binding ability of
      neutrophils to IC, in spite of a large numbers of neutrophils accumulation.
      Consequently, the immune-reaction induced by alginate makes clinical prognosis of
      such patients more intractable.

PMID- 9621568
TI  - [Study on pathogenetic role of myeloperoxidase, tumor necrosis factor alpha,
      interferon gamma in chronic airway infection with Pseudomonas aeruginosa].
AB  - This study was performed to demonstrate the pathogenetic role of mucoid-alginate
      produced by Pseudomonas aeruginosa in relation to immuno-interaction in host
      cells. The obtained results are as follows. 1. Clinical Observation The
      concentration of MPO, TNF alpha, and IFN gamma in peripheral blood of 37 cases of
      chronic airway infection were observed. The cases were divided into the groups
      with mucoid strain positive (21 cases) and negative (16 cases), and each group
      was also divided into subgroups with active clinical symptom and without. High
      concentration of serum IFN gamma was shown in the group of mucoid strain positive
      cases (0.10 +/- 0.08 IU/ml in healthy volunteers group, 0.54 +/- 0.56 IU/ml in
      mucoid group with symptom: p < 0.01, 0.09 +/- 0.15 IU/ml in mucoid group without
      symptom, 0.13 +/- 0.13 IU/ml in non-mucoid group with symptom, 0.09 +/- 0.13
      IU/ml in non-mucoid group without symptom). But plasma concentrations of MPO and
      serum concentrations of TNF alpha were not increased in all groups, except MPO in
      non-mucoid group with symptom. It indicates that IFN gamma has a characteristic
      role in chronic airway infection with mucoid Pseudomonas aeruginosa (P.
      aeruginosa). 2. Experimental Observation One hundred twenty-two of alginate
      immunized mice were made by 5 times of intraabdominal injection with purified
      alginate extracted from mucoid P. aeruginosa PT-1252. 4 x 10(6) CFU/body of
      mucoid P. aeruginosa PT-1252 or 20 micrograms/body of purified alginate was
      intubated per trachea into the immunized mice, and changes in mean fluorescence
      intensity (MFI) of MPO and TNF alpha on neutrophils and IFN gamma on CD3 positive
      lymphocytes in BALF were observed. MFI of MPO (99.7 +/- 16.5-->177.0 +/- 23.1: p
      < 0.001) and TNF alpha (59.2 +/- 13.3-->197.0 +/- 62.0: p < 0.001) were increased
      on day 2 and they were kept up till on day 30 in P. aeruginosa group. But in
      alginate group they were temporally decreased on day 2, and they were gradually
      increased (MPO: 99.7 +/- 16.5-->212.6 +/- 12.1: p < 0.001, TNF alpha: 59.2 +/-
      13.3-->162.4 +/- 30.9: p < 0.01). The temporally decrease of MPO and TNF alpha on
      day 2 in alginate group may suggest that a large amount of alginate inhibits
      neutrophils chemotaxis. MFI of IFN gamma in P. aeruginosa was also increased
      (110.0 +/- 32.9-->198.3 +/- 23.0: p < 0.01) on day 2 and it was gradually
      decreased on day 30 (156.0 +/- 13.8). In alginate group, MFI of IFN gamma in BALF
      was increased on day 5 (110.0 +/- 32.9-->201.0 +/- 49.3: p < 0.001) and kept a
      high level till day 30 (223.0 +/- 57.5: p < 0.01). In morphological, the moderate
      grade of lymphocytes infiltration observed in intersitial area of lung tissue on
      both groups of P. aeruginosa and alginate intubation mice. The findings was
      continuously seen from day 5 through day 30. The lymphocytes infiltration
      appeared in lung tissue can be though as an result of immuno-interaction with IFN
      gamma positive lymphocytes and mucoid-alginate. Inferences are drawn from the
      clinical results and the experimental ones that the CD3 positive IFN gamma
      lymphocytes expressed by immunological interaction with mucoid-alginate and the
      IFN gamma lymphocytes (Th1 like cells) plays an important role on advancement of
      chronic airway infection with mucoid P. aeruginosa.

PMID- 9621569
TI  - [A case of solitary pulmonary nodule caused by Mycobacterium avium].
AB  - A 56-year-old male without respiratory symptoms, past history nor familial
      history, was admitted to our hospital because of pulmonary solitary nodule on the
      chest radiograph. Computed tomograph showed a smooth surface nodule in the left
      lower lobe (segment 8). Bronchofiberscopy could not give any specific
      histological findings nor bacteriological findings, therefore the patient
      underwent partial pulmonary resection by videoassisted thoracoscopic surgery.
      Pathology of the resected specimen revealed epithelioid cell granuloma with giant
      cells but not any acid-fast bacilli. He was treated with rifampicin and isoniazid
      for "tuberculoma". After three weeks, thirty colonies grew on an Ogawa's egg
      medium, which were identified as Mycobacterium avium by PCR. There are few
      reports about the solitary pulmonary nodule due to M. avium-intracellurale
      complex infection, however, it is supposed that there are many "tuberculoma's"
      without bacteriological differentiation between tuberculosis and nontuberculous
      mycobacterial infection. It is difficult to diagnose a solitary pulmonary nodule
      caused by nontuberculous mycobacterial infection with bronchofiberscopy, and the
      location of the lesion is usually subpleural, therefore it is thought that
      videoassisted thoracoscopic surgery is valied for the diagnosis of solitary
      pulmonary nodule due to nontuberculous mycobacterium.

PMID- 9621570
TI  - [A patient with Streptococcus intermedius brain abscess treated with high dose
      penicillin G--susceptibility of the isolate to penicillin G and the concentration
      of penicillin G in cerebrospinal fluid].
AB  - We report here a 2-year-old boy with a Streptococcus intermedius brain abscess
      and bilateral ventriculitis successfully treated with a high dose penicillin G
      (200,000 U/kg/dose, 6 times a day, 1 hour continuous infusion). Although
      hydrocephalus residuced, the high dose penicillin G therapy cured his brain
      abscess and bilateral ventriculitis. The minimal inhibitory concentration of
      penicillin G to the isolate was 0.008 microgram/ml. The penicillin G
      concentration in the cerebrospinal fluid after 2 hours from the infusion was
      about 5 micrograms/ml. S. intermedius must be considered as one of the causative
      agents for brain abscess. High dose penicillin G therapy is one choice of
      treatment for brain abscess due to penicillin-susceptible streptococci.

PMID- 9621571
TI  - Two cases of adult varicella accompanied by hepatic dysfunction.
AB  - Varicella is a typical acute exanthematous viral infection caused by varicella
      zoster virus (VZV). In recently years, as far as hepatic dysfunction caused by
      viruses other than the hepatitis virus is concerned, there have been a few
      reports on hepatic dysfunction accompanying varicella following organ
      transplantation of Europe and America and another report on an immunocompromized
      adult following treatment for Systemic lupus erythematosis (SLE) in Japan.
      Nonetheless, we searched the MEDLINE and J MEDICINE listing the publications
      between 1986 and 1996 and found one report on healthy adults with varicella
      accompanied by hepatic dysfunction in Europe and America and two reports in
      Japan. Only Noguchi et al. dealt with the findings of liver biopsy. We examined
      two healthy adults with varicella and mild-to-moderate hepatic dysfunction, and
      referred to the results of their liver biopsies. The present paper discusses this
      issue, citing some references.

PMID- 9621572
TI  - [Clinical chemistry of atherosclerosis].

PMID- 9621573
TI  - [Determination of lipid composition of high density lipoproteins by thin-layer
      chromatography on silica gel].
AB  - Unidimensional chromatography in a thin layer of silica gel with two solvent
      systems for separation of the lipid extract of high density lipoproteins (HDLP)
      detected 10 lipid fractions in subjects with normal lipidemia. Four phospholipid
      fractions were identified: three main (phosphatidylcholine,
      lysophosphatidylcholine, and sphingomyelin) and one minor,
      phosphatidylethanolamine. HDLP lipids include free cholesterol and its esters;
      three glyceride fractions are detected: mono- di, and triglycerides, and free
      fatty acids. The ratio of individual phospholipid fractions and of free to ester
      bound cholesterol in HDLP determined by computer-aided densitometry of
      chromatograms coincides with the data obtained routinely. Such a method for
      assessing the HDLP lipid composition is useful in studies of HDLP in patients
      with disorders of HDLP metabolism and for assessing the changes in HDLP
      composition during hypolipidemic therapy.

PMID- 9621574
TI  - [Activities of glutathione enzymes in liver biopsy specimens in chronic lesions
      of hepatocytes].
AB  - The nonenzymatic conjugation of metabolites is decreased in chronic diseases of
      the liver, which is caused by decreased concentration of glutathione. The
      activities of glutathione enzymes are increased, this indicating the development
      of compensatory processes of mobilization of the second phase of detoxication,
      that is, increased conjugation under conditions of suppression of the cytochrome
      P-450 system. Measurement of liver glutathione transferase is a highly
      informative test for assessing the activity of the pathological process,
      particularly important in patients with chronic active hepatitis and cirrhosis of
      the liver.

PMID- 9621575
TI  - [Effect of glucose on the aqueous infrared spectrum (bloodless determination of
      blood glucose by tissue photometry)].
AB  - The creation of a noninvasive (without blood collection) method for measuring
      blood glucose concentrations, convenient for patients, is practically important,
      because the treatment of diabetics requires constant many-year monitoring of the
      alimentary component of glycemia. Use of IR spectra is impeded by the
      interference of strong bands of water absorption, whose concentration in the
      tissues is almost 1000 times higher than that of glucose. We investigated the
      effects of glucose, albumen, and blood serum on the structure of water absorption
      bands in the 1400-1600, 960, 1153, and 2000-2400 nm bands. The method of
      differentiated spectra was used. Glucose cleaved the negative aqueous band on the
      differential spectrum with 1410 and 1455 nm peaks and a positive 1590 nm peak
      with the isobestic point at 1540 nm. Albumen and serum proteins caused similar,
      although somewhat different effects, not preventing the use of the above
      wavelengths for the creation of a noninvasive device, because the concentrations
      of proteins and electrolytes are not changed after food intake if the homeostasis
      is intact.

PMID- 9621576
TI  - [Significance of daily hydroxyprolinuria in the early diagnosis of
      nephrosclerosis in patients with chronic pyelonephritis].
AB  - Studies of daily excretion of hydroxyproline with the urine in patients with
      chronic pyelonephritis (CP) showed manifest hyper-hydroxyprolinuria at the early
      stages of the disease, which augmented with the development of renal
      insufficiency. Measurement of hydroxyproline in the urine of CP patients is
      proposed as a test reflecting the renal connective tissue metabolism at the early
      stages of the disease. It can be used for assessing the activity of the sclerotic
      process in the kidneys of CP patients, for predicting the disease course and
      outcome, and, probably, for developing methods of adequate pathogenetic therapy
      based on biochemical monitoring. The method is noninvasive, sufficiently
      informative, and available for clinical diagnostic laboratories.

PMID- 9621577
TI  - [Characteristics of clinical laboratory diagnosis in childhood].

PMID- 9621578
TI  - [Immunoenzyme method of lactoferrin analysis].
AB  - The authors propose a highly effective method for isolation of lactoferrin from
      female colostrum. Lactoferrin is measured by the sandwich enzyme immunoassay. Its
      concentrations in the serum, urine, amniotic and cerebrospinal fluid in health
      are measured. The advantages of the method for lactoferrin purification and the
      practical significance of this protein are discussed.

PMID- 9621579
TI  - [Materials for performing external quality control of the measurement of
      ceruloplasmin activity].
AB  - Quaternary monophosphonium compound 1-triphenyl phosphoniomethyl naphthalene
      bromide stabilizes blood serum samples and preserves the activity of
      ceruloplasmin (CP 1.16.3.1) intact for 30 days. For preparing the reference
      material, 10 ml of serum is added to 190 ml of 1.55 mM solution of this compound,
      left for 24 h at 4-8 degrees C, poured in small flasks, stored at the same
      temperature, and used as reference material as needed for checking up the
      correctness of ceruloplasmin measurements in biochemical laboratories.

PMID- 9621580
TI  - [Clinical and hematological significance of antigranulocyte autoantibodies].
AB  - Sera of thirty patients with acute and chronic immune neutropenias for different
      target cells: polymorphonuclear leukocytes (PMNL), macrophages, T and B
      lymphocytes are studied. An increase of the level of antigranulocyte antibodies
      is associated with a decrease of PMNL count, whereas a decrease of these
      antibodies' level is paralleled by an increase of the neutrophil count. It is
      noteworthy that the sera of patients with acute neutropenias contain
      autoantibodies similar to antibodies to CD13 antigen, which react mainly with the
      neutrophils. The sera of patients with chronic neutropenias contain antibodies
      similar to anti-CD45 antibodies and react with all target cells.

PMID- 9621581
TI  - [Diagnostic value of several immunity parameters in gestoses].
AB  - Gestosis is a grave complication of pregnancy. Assessment of its severity in
      various pregnancy terms is important for making decision about preterm delivery
      and predicting the outcome of pregnancy. The authors consider that such
      immunological tests as measurement of circulating immune complexes, NBT test, and
      cytological index of activity are reliable indicators of the severity of
      gestosis, which can be used for predicting the condition and its development.

PMID- 9621582
TI  - [Detection of rheumatoid factor in the blood of patients by latex agglutination].
AB  - A highly effective rapid method is developed for detecting the rheumatoid factor
      in human serum. Polystyrene suspension-based latex conjugate is synthesized,
      representing a styrene and methacrylic acid copolymer. The immunospecific reagent
      is human IgG. The resultant latex conjugate can be used in practical medicine for
      analysis of the rheumatoid factor.

PMID- 9621583
TI  - [Sequential Bayes' strategy and mechanism of decision making in the OMIS
      software].
AB  - The paper describes the method of image recognition in which a useful element of
      Bayes' approach, numerous alternatives, is united with the productive idea of
      heterogeneous sequential analysis--ordering of signs by their informative value
      for decision making. The idea of the method--a sequential Bayes' algorithm-
      consists in the following: the a priori probabilities are not determined before
      hand but specified in turn, depending on the empirical material. The author
      proves that algorithms conforming to the Neumann-Pierson or Wald strategies,
      specifically, the heterogeneous sequential algorithm, are not to be referred to
      the Bayes' algorithms, as is usually done in analyses of clinical laboratory
      data. Ideologically the heterogeneous sequential algorithm was developed as a
      method for analysis of empirical data, whereas the Bayes' approach is a deductive
      method. Confusion of the Bayes' approach with the algorithms based on the
      probability ratios is methodologically unjustified at least because the Neumann
      Pierson and Wald's approaches are the greatest statistical achievements of the
      twentieth century and have nothing to do with the Bayes' formula. The methodology
      of constructing the probability measure in the clinical laboratory signs space is
      described in detail, as are the new objects, interval and binary structures,
      which emerge in the course of this construction. These objects help improve the
      diagnostic significance of clinical laboratory information even in cases when the
      results of analyses are apparently normal. The sequential Bayes algorithm is
      compared with the traditional Bayes approach to certain clinical problems. The
      author concludes that the sequential Bayes algorithm is a serious alternative to
      algorithms for making multiple-alternative decisions in the solution of clinical
      tasks.

PMID- 9621584
TI  - [Time to analyze the attitude towards alternative medicine. The patient must be
      allowed to look for safety ian comfort in more than one place].

PMID- 9621585
TI  - [Excellent results of mammography screening. Still balancing between cost-benefit
      analysis].

PMID- 9621587
TI  - [Offensive primary health care in spite of budget cuts].

PMID- 9621586
TI  - [Are minor surgical procedures necessary!].

PMID- 9621588
TI  - [What will happen to medical documentation?].

PMID- 9621589
TI  - [Patients in health care--easy to read about rights, responsibility, ethics].

PMID- 9621590
TI  - [Holistic view is important in the treatment of patients with life problems].

PMID- 9621591
TI  - [There are rules on drug prescription].

PMID- 9621592
TI  - [Primary health care as a buffer for emergency hospitals].

PMID- 9621593
TI  - [Empathy is not sympathy].

PMID- 9621594
TI  - [A revolutionary Japanese method for treatment of lymphangioma].
AB  - Large cystic lymphangiomas of the neck (hygroma colli) have traditionally been
      treated surgically or by local injection of various sclerosing agents. Owing to
      the infiltrative growth of these cysts, radical surgery has often been difficult
      due to the risk of damage to nerves and adjacent organs; and the use of available
      sclerosing agents has often resulted in disfigurement due to extensive scarring,
      thus rendering secondary surgery even more difficult. However, OK-432, a new
      agent for local injection, has been tested with good results, especially in
      Japan. In five consecutive paediatric cases of lymphangioma, we found ultrasound
      guided injection of the cysts with OK-432 to yield good response without
      complications. In three cases, the lymphangioma disappeared leaving the child's
      appearance quite normal, and there has been no recurrence. In one case, the
      lymphangioma disappeared but apparently recurred within half a year (during which
      time we had lost contact with the family). This was the only case of small cysts
      (cavernous lymphangioma), which are putatively more resistant to OK-432. The only
      child to be operated also had thoracic lymphangioma which was not injected,
      though the cervical part which was injected was reduced by 50 per cent pre
      operatively, the final outcome being excellent with no visible cysts in any
      region. Thus, hitherto our results suggest the therapeutic effect of OK-432 to be
      good, and further clinical investigation is planned.

PMID- 9621595
TI  - [Schools are occupational environments for children. The risk of physical or
      psychological "occupational injuries" must be taken seriously].

PMID- 9621596
TI  - [A new study of patients with cancer in Umea alternative medicine is no
      alternative].
AB  - A questionnaire study comprising 854 cancer patients in the Umea health care
      region and covering the 10-year period, 1987-96, showed only a few cancer
      patients to use alternative medicine treatment for their disease. As compared
      with 19.4 per cent of 144 residents selected from the population register who
      answered the questionnaire in 1987, 16.8 per cent of the cancer patients reported
      using alternative treatments in 1987, 14.4 per cent in 1990, and 16.4 per cent in
      1996. The commonest forms of alternative medicine used were chiropractic and
      acupuncture, and the majority of treatments were for pain in the muscles or
      musculoskeletal system.

PMID- 9621597
TI  - [The mentally retarded are not adequately treated for somatic diseases.
      Psychiatry and primary health care services should share responsibility].

PMID- 9621598
TI  - [Did Dracula suffer of pellagra or pica?].

PMID- 9621599
TI  - [Non-invasive respirator care has ethical advantages. Patients can make their own
      decisions].

PMID- 9621600
TI  - [Ritual circumcision of small boys is barbaric].

PMID- 9621601
TI  - [From Paracelsus to Clarence Blomquist].

PMID- 9621602
TI  - [The status of and outlook for the development of parenteral nutrition in
      Ukraine].

PMID- 9621603
TI  - [An analysis of morbidity in those who worked in the cleanup of the aftermath of
      the Chernobyl accident].
AB  - Some aspects were studied of pathologies in those liquidators who sought to find
      out connection between health disorders and restorative work at the Chernobyl
      Power Plant through the Kiev Regional Expert Medical Counsel in 1990-1996. Those
      disorders in whose pathogenesis the radiation factor acts together with factors
      of nonradiation nature, namely of the nervous, cardiovascular systems, and
      digestive organs, rank first in the structure of pathologies during the first ten
      years of the postradiation period. The incidence rate of malignancies among those
      liquidators who had applied to the Council is on the increase. In the structure
      of oncopathologies prevalence, the leading place is taken up by tumours of
      digestive organs, respiratory system, and urogenital organs.

PMID- 9621604
TI  - [The characteristics of the clinical course of rheumatic diseases in persons
      subjected to the effect of ionizing radiation after the accident at the Chernobyl
      Atomic Electric Power Station].
AB  - Results are submitted of clinical, laboratory and immunological studies in
      patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE),
      systemic scleroderma (SSD), with n = 386, 35, 23 respectively, who had been
      exposed to ionizing radiation from the ChPP reactor accident. In the above
      patients, serum interferon (SI) levels were found out to be increased while those
      of natural killer cells (NKs) decreased by comparison with healthy donors; NKs
      appeared to be significantly lower (P < 0.001) in SLE and SSD patients than they
      were in RA ones and healthy subjects.

PMID- 9621605
TI  - [The pathomorphological characteristics of duodenal peptic ulcer in the victims
      of the accident at the Chernobyl Atomic Electric Power Station: changes in the
      gastric mucosa].
AB  - Gastrobiopsies were studied from patients with duodenal ulcer, 62 of whom took
      part in the elimination of the effects of the Chernobyl Nuclear Power Plant
      breakdown, 33 were permanent residents in the territories affected by radioactive
      contamination, and 36 formed the control group. Several distinguishing features
      were noted in chronic Helicobacter gastritis in victims of Chernobyl accident
      versus control, such as higher degree and activity of the inflammatory process
      spreading over large tissue areas, with Helicobacter pylori being recordable in
      the gastric mucosa in highly increased numbers, and more frequent occurrence of
      atrophic changes. Incorporation of radionuclides and external irradiation at dose
      levels exceeding 25 cause most significant disturbances in regeneration of
      epithelium, with its enterolyzation and dysplasia going on, which fact makes the
      risk of neoplastic transformations higher.

PMID- 9621606
TI  - [The pathomorphological characteristics of duodenal peptic ulcer in the victims
      of the accident at the Chernobyl Atomic Electric Power Station: changes in the
      duodenal mucosa outside of the defect].
AB  - A study was made of duodenobiopsies from patients with duodenal ulcer, 62 of whom
      took part in the elimination of the effects of the Chernobyl Nuclear Power Plant
      accident, 33 have been resident in the territories affected by radioactive
      contamination, and 36 were a group of nosological control. In the ChNPP accident
      victims, the inflammatory process in chronic duodenitis tended to be more
      pronounced and active, with the atrophic changes in the mucous membrane being
      more commonly seen. Incorporation of radionuclides and external irradiation in a
      dose exceeding 25 sGy causes most profound disturbances in regeneration of
      epithelium entailing metaplasia and dysplasia of gastric epithelium in duodenum,
      which facts heighten the risk for neoplasmogenesis.

PMID- 9621607
TI  - [The clinico-morphological characteristics of myeloid leukemias under the current
      ecological conditions in Ukraine].
AB  - Results are submitted of examination of 93 bone marrow trepanobiopsies from iliac
      bone of patients with acute and chronic leukemia they developed during 1993-1996.
      Some aspects are considered of haemopoiesis and stromal elements together with
      morphological features of the medical problem in question in present-day
      environmental health-hazard conditions. With AML and CML running aggressive
      course, the incidence rates of granulocytic and megakaryocytic CML being on the
      increase, the outlook for tomorrow is not bright. All this (emergence of tissue
      optically dense "dark impregnations" are also worthy of mention in this context)
      is deemed to bear relation to adverse ecological conditions nowadays.

PMID- 9621608
TI  - [A complex of methods for the early diagnosis of premorbid states of the
      bronchopulmonary system and of the main forms of chronic nonspecific lung
      diseases in those who took part in the cleanup of the aftermath of the accident
      at the Chernobyl Atomic Electric Power Station].
AB  - The author suggests including questionnaire survey, recording of the external
      respiration, and thermography into a complex of methods for early diagnosis of
      premorbid states of the bronchopulmonary system and main forms of chronic
      unspecific lung diseases in those persons who took part in the elimination of the
      aftereffects of the ChNPP breakdown. The above complex can be used as a screening
      for contingents to be put to further in-depth study.

PMID- 9621609
TI  - [The bioelectrical activity of the brain in an organic lesion of the central
      nervous system presenting in those who worked in the cleanup of the aftermath of
      the accident at Chernobyl Atomic Electric Power Station].
AB  - A study was made of brain bioelectric activity in 122 patients who developed
      organic lesions of the brain following their taking part in the elimination of
      the effects of Chernobyl disaster. A visual analysis was performed as was an
      assessment of the electroencephalogrammes (EEG) obtained, as recommended by E. A.
      Zhirmunskaia. Disorganization of bioelectrical activity occurred in organic
      lesions of the brain in 26.5% of cases, which fact suggested disturbances in the
      activity of control systems of the brain. Disorganized EEG with marked
      disturbances in both cortical and regulatory electrogenesis were common in
      patients presenting with psycho-organic syndrome. The results obtained will, we
      believe, help in elucidating one of the links in the pathogenesis of the above
      conditions and selecting a complex of adequate therapeutic measures to be
      instituted in his pathology treatment setting.

PMID- 9621610
TI  - [General trends in the pathomorphosis of surgical diseases of the thyroid after
      the Chernobyl catastrophe].
AB  - An analysis is presented of changes in the patterns of surgical pathologies of
      the thyroid gland that had occurred during the 15-yr follow-up of the Kiev Region
      representatives operated on in a specialized clinic facility. Increase in the
      incidence rates of autoimmune Hashimoto's thyroiditis, benign and malignant
      tumours of the thyroid gland--such were main trends in pathomorphosis of
      thyroidal pathologies having been noted during the post-ChPP accident years.
      Increase in the number of cases of carcinoma with concurrent hyperplastic and
      autoimmune thyroid diseases attests to the need for a comprehensive evaluation of
      patients presenting with different forms of goiter as well as for their surgical
      treatment in a timely fashion.

PMID- 9621611
TI  - [The status of lipid metabolism and free-radical processes in workers in a 30
      kilometer exclusion zone].
AB  - Patterns were studied of lipid metabolism as was the state of free radical
      processes in different groups of those individuals working within a 30-km zone of
      estrangement depending on the length of time they stayed there. Atherogenically
      directed changes in blood lipid spectrum and processes of lipid peroxidation
      identified under working conditions in the zone of estrangement appeared to be
      more pronounced in subjects working at the object Ukryttia [correction of
      "Ukrytiye"] (Shelter) than in those in the zone working outside the object
      Ukryttia [correction of "Ukrytiye"].

PMID- 9621612
TI  - [Morbidity with temporary loss of work capacity in workers in the operational
      jobs of the main metallurgical manufactures].
AB  - Study into morbidity involving temporary unfitness for work among workers of
      operating vocations in the basic metallurgy industries versus those working in
      the repair-and-machine shops, maintenance workshops, revealed high levels of
      temporary disability in the former working populations, especially in respect of
      such health disorders as diseases of the digestive organs, affections of the
      nervous, cardiovascular and osseomuscular systems, that were noted to go upwards
      with length of service and age of the workmen. Significant differences in
      morbidity pattern and level in vocational groups as a whole and in respect of
      classes of disorders and nosological forms were found out to be related to labour
      pattern and its conditions, degree of strain, physical strength and mental
      concentration the work to be done was demanding of, level of exposure to adverse
      occupational factors common in metallurgy industry. Methodical recommendations
      have been worked out concerning preventive strategies toward occupational health
      problems.

PMID- 9621613
TI  - [Psychoemotional disorders in those working with epoxy compounds].
AB  - Psychoemotional status was studied in 125 female workers 21 to 50 years old
      having been exposed to epoxide resins and their compounds for 5 to 25 years. We
      undertook to carry out multifactor questionnaire survey together with
      pathopsychological testing, and determining levels of personal constitutional and
      reactive anxiety. Occupation-related neurotic disorders (neurasthenic-, obsessive
      and phobic-, and, to a lesser extent, hysterical type manifestations) were found
      out to develop during the stage of prenosologic forms against the background of
      high level of both constitutional and reactive anxiety. It is
      psychoconstitutional traits of workers being predisposing factors for the
      disorders in question that affect the epoxide-related origination and development
      of psychoemotional derangement. The following traits can be regarded as
      predisposing factors for derangement: excitability, bias towards anxiety,
      deestiming, demonstrable behaviour.

PMID- 9621614
TI  - [The structural-metabolic damages to the myocardium in acute coronary failure].

PMID- 9621615
TI  - [Intravascular microcoagulation of the blood in diseases of the pancreas, stomach
      and intestines].

PMID- 9621616
TI  - [The stomach microflora in peptic ulcer and chronic gastritis].

PMID- 9621617
TI  - [The pathogenetic mechanisms of an ischemic stroke].

PMID- 9621618
TI  - [Sorption agents in the surgery of suppuration].

PMID- 9621619
TI  - [Platelet activating factor and its role in the pathogenesis of immune
      glomerulopathy].

PMID- 9621620
TI  - [The importance of differentially amplified electrocardiography for the detection
      of accessory atrioventricular conduction pathways in paroxysmal tachycardias].

PMID- 9621621
TI  - [The evaluation of left ventricular diastolic function in patients with type-1
      diabetes mellitus].
AB  - Diastolic transmitral bloodflow (TMBF) was studied in 42 patients with type I
      diabetes mellitus (DM) and 46 essentially healthy subjects in rest and during
      wrist isometric load. In rest, the auricle role in the left ventricular (LV)
      filling got enhanced but indices for early filling did not undergo changes as
      compared to controls. In exposure to the load, alterations in TMBF patterns in 25
      DM patients were different from the reaction in healthy subjects. In this
      subgroup of patients presenting with disturbed LV filling average patient age was
      greater, duration of illness longer than in 17 patients free form diastolic
      dysfunction (DD). Indices for early filling were low in DD patients even in rest
      whereas in those without DD the above indices tended to increase as compared to
      controls. Sympathetic hyperreactivity characteristic of DM patients can in part
      mask reduction of rate of early filling caused by disturbances in relaxation. A
      conclusion was reached that pulse dopplerography can be used as a screening test
      to identify DM patients presenting with DD.

PMID- 9621622
TI  - [The function of the thyroid and thyrotropic function in patients with chronic
      ischemic heart disease and rhythm disorders].
AB  - Measured in 119 patients with chronic heart disease (exercise-induced angina in
      62, cardiosclerosis in 57 cases) presenting with arrhythmias (extrasystolic
      arrhythmia, permanent form cardiac fibrillation, association of cardiac
      fibrillation with ventricular arrhythmia, with n = 58, 38, 23 respectively) were
      blood levels of thyroid-stimulating hormone (TSH), triiodothyronine (T3) and
      thyroxin (T4) using immunoradiometric assay. In extrasystolic arrhythmia,
      permanent form cardiac fibrillation, there were no deviations from the norm in
      the basal TSH blood levels, reduction in (T3) as well as augmentation of (T4) in
      cardiac fibrillation. With permanent form cardiac fibrillation associated with
      ventricular arrhythmia the TSH blood level got decreased, the (T3) and (T4)
      content undergoing no changes The posttreatment blood content of (T3) tended to
      augment in extrasystolic arrhythmia.

PMID- 9621624
TI  - [Lipid peroxidation in patients with chronic gastritis].
AB  - Activity was studied of lipid peroxidation (LPO) in 50 patients with chronic
      antral gastritis (ChAG) in the phase of exacerbation. Accumulation of products of
      the oxidation reaction such as conjugated dienes and trienes, tetraenes, together
      with the total content of oxidated compounds commonly named as oxodienic
      conjugates indicated LPO activity. A conclusion was reached to the effect that in
      ChAG during the phase of exacerbation there takes place an activation of LPO in
      the mucous membrane. A trigger element involving this mechanism of injury is
      thought to be destructive action of factors of virulence of Helicobacter
      infection on the epitheliocyte cellular membrane. If the cell antioxidant defence
      is capable of keeping the LPO processes on a certain increased level the lesion
      evolves mainly through general degenerative alterations in the gastric epithelium
      leading to atrophy of the mucous membrane, necessitating supplementing ChAG
      metabolic therapy at its early stages with cytoprotectors capable of suppressing
      Helicobacter infection, as well as antioxidants, stimulants of the protein
      synthetizing processes, drug preparations improving the microcirculation.

PMID- 9621623
TI  - [The tonus of Oddi's sphincter and gallbladder contractility in patients with
      chronic cholecystitis].
AB  - As many as 163 young male patients with chronic noncalculous cholecystitis were
      studied for motility of the biliary tract. Normal findings were in 15.9% of
      cases. Hypocontractility of the gallbladder, hypermyotonia of the Oddi sphincter
      (with 33.7% and 44.2% respectively), and concurrent presence thereof were the
      most commonly seen types of dyskinesia. The results obtained suggest that the
      above abnormalities in motility of the biliary tract may have a part in the
      origination and/or progression of chronic cholecystitis.

PMID- 9621625
TI  - [Lipid peroxidation in patients with diffuse toxic goiter and hypothyroidism].
AB  - A study made in 77 patients with different form of thyropathy revealed increased
      blood plasma and erythrocyte content of lipid peroxidation products, such as
      diene conjugates and TBA-active producers. The plasma chemiluminescence got more
      intense as well. Different mechanisms for the lipid peroxidation activation in
      patients presenting with thyroid hormone abundance or deficiency have been
      analyzed.

PMID- 9621626
TI  - [The effect of the xenotransplantation of pancreatic islet cells on the indices
      of lipid metabolism and the proteolytic system in patients with diabetic
      angiopathy].

PMID- 9621627
TI  - [Laboratory diagnostic methods in primary pulmonary tuberculosis in adults].
AB  - A comprehensive clinical and roentgenological evaluation was done in 495 patients
      with primary tuberculosis aged more than eighteen. The clinical pattern of
      primary forms of the specific process was characterized by predominance of
      tuberculosis of intrathoracic lymph nodes (tumorous form) infiltrative
      tuberculosis of pararoot or lower-lobe localization, and exudative pleurisy.
      Primary tuberculosis was diagnosed in 56.4% of adults. Examination of sputum for
      changed forms of MBT increases the frequency of verification of diagnosis by
      16.0% in comparison with conventional microbiological assays. Primary
      tuberculosis of the respiratory system in 63.5% of adults runs its course against
      the background of significant disorders of T- and B-systems of lymphocytes,
      antituberculous immune defence and bodily metabolic processes. The use of a
      complex of immunologic studies was found to promote the accuracy of diagnosis of
      primary tuberculosis from 56.4% up to 79.6%, that of biochemical ones-from 56.4%
      to 77.5%.

PMID- 9621628
TI  - [The characteristics of spirographic methods for detecting bronchial
      hyperreactivity].
AB  - Overall thirty-nine patients were studied, their clinical and immunological
      indices suggesting atopic form of bronchial asthma (BA), as were eighty children
      presenting with recurrent episodes of obstructive bronchitis. With PC2OH test
      being used to identify unspecific hyperreactivity of bronchi in BA patients
      actual positive results are recordable more often than they are with calculation
      of the parameter characterizing lability of bronchi, while false positives are
      less common. There were also more false positives with PC2OH test than they were
      the method of comparison.

PMID- 9621629
TI  - [The dynamic indices of the hemopoietic status in patients with acute
      lymphoblastic leukemia].

PMID- 9621630
TI  - [The ultrastructure of the natural killer cells in transitional-cell bladder
      cancer].
AB  - Electronic microexamination of two of the 65 cases of transitional cell
      carcinoma, in which cases we succeeded in detecting and studying the interaction
      between the natural killer cells and a target cell, suggested that a natural
      killer cell might be an active element of tissue immunity being capable of
      recognizing and destroying cells that differ in their genetic apparatus from
      normal cells and bodily tissues. The main targets of natural killer cells are
      those organelles in tumour cells that are their most active units of vital
      importance, the destruction of which is aimed at maintaining of tissue and
      cellular homeostasis.

PMID- 9621631
TI  - [The screening of immune donors in organized collectives].
AB  - Use of blood of reconvalescents from infectious diseases along with screening of
      blood from non-immunized donors permits procuring new sources of immune blood
      preparations with high content of specific antibodies (keeping strictly to the
      existing normative-instructional documents on donorship). Screening of immune
      donors in military collective bodies is a worth-while exercise both in medical
      and organizational respects owing to the contingents being homogeneous in sex,
      age and physiologic status.

PMID- 9621632
TI  - [Antibody production in the blood of donors immunized with staphylococcal
      anatoxin].
AB  - Blood serum content was studied of specific antistaphylococcal antibodies
      (staphylolysins) in 576 donors immunized with staphylococcal anatoxin with the
      purpose of obtaining an antistaphylococcal plasma and antistaphylococcal
      immunoglobulin to be used in clinical settings. 292 donors had been immunized and
      examined prior to 1986, 284--after 1986 (before 1994). Comparison of the immune
      responses in the above periods of time permitted finding out that 13.03% of
      immunized donors responded to the antigenic stimulus by such paradoxical reaction
      as disappearance of specific antibodies; the number of persons-active respondents
      has gotten reduced from 17.12% to 5.98% as has the number of individuals having
      the baseline level of staphylolysins (1-2 ME/ml). The changes were at their
      greatest in donors with group A (II) blood.

PMID- 9621633
TI  - [The role of immune and microcirculatory disorders in the pathogenesis of late
      pregnancy gestoses].
AB  - A total of 92 pregnant women with late gestoses were examined, inclusive of 25
      (27.2%) women presenting with hydrops, 64 (69.6%) with a first-to-third degree
      nephropathy, 3 (3.3%) with preeclampsia. All the examinees revealed clear-cut
      disorders of the immune homeostasis and microcirculation that tended to be more
      pronounced in a third-degree nephropathy and preeclampsia. Correlation was
      established between parameters characterizing immunity and microhaemodynamic
      indexes, which fact suggests community of their pathogeneses.

PMID- 9621634
TI  - [The colonization resistance of the tonsils in healthy and frequently ill
      children].
AB  - State of colonization resistance was studied in healthy children and those
      presenting with recurring infectious and inflammatory diseases of the upper
      respiratory tract. Identification of representatives of tonsil anaerobic and
      aerobic floras was carried out. Lactic acid bacteria (LAB), alpha-Streptococcus,
      were present in tonsil flora of healthy children. Pathogenic microorganisms and
      opportunistic pathogens were recoverable from always ailing children with
      tonsillitis, with alpha-streptococcus being recoverable very seldom and no
      decrease in LAB levels being seen. In patients--candidates for tonsillectomy,
      pathogenic microorganisms were identifiable, with LAB levels decrease by a factor
      of 10(3-4). The above findings suggest development of dysbacteriosis, decrement
      of tonsil colonization resistance in always ailing children, which fact is to be
      considered in designing and implementing therapeutic measures.

PMID- 9621635
TI  - [The neurological mechanisms regulating normal eye movements and in pathology].
AB  - On the basis of critical analysis of the main periodicals and relevant references
      as well as personal clinical experience the author submits his idea on
      substantiation of mechanisms of ocular movements regulation, for which purpose he
      uses evolutionary principles of development of the nervous system. Depending on
      the levels of disease foci as well as nature thereof and pattern of the pathology
      in question, the author has identified syndromological complexes of oculomotor
      disorders, including the original ones having pathognostic significance in
      respect of CNS functional abnormalities as well as of demyelinating and
      infectious processes. He gives his view on pathogenesis of development of those
      oculomotor disorders posing a problem in differential diagnosis, regarding it as
      consequence of dominating of injury to particular efferent structures of brain
      truncal formations.

PMID- 9621636
TI  - [Current approaches to the treatment of patients with systemic scleroderma].
AB  - Principles are highlighted of modern therapy of systemic scleroderma involving
      prescription of basis agents, such as, in the first place, thiol compounds as
      well as drugs affecting certain links of the disease pathogenesis, in particular,
      antifibrotic, vasodilative, anti-inflammatory ones. Methods are presented of
      therapy of systemic scleroderma with unithiol and superelectrophoresis of
      unithiol with dimexide, developed by the author. Syndrome therapy of the disease
      is characterized taking account of damage to certain organs and systems.

PMID- 9621637
TI  - [The assessment of the work capacity of myocardial infarct patients rehabilitated
      in the hospital under an accelerated program].
AB  - Results are submitted of long-term follow-up of patients with macrofocal
      myocardial infarction who had been rehabilitated in an in-patient setting by the
      accelerated programme and resumed their work 2.5 months following the onset of
      the illness. The above patients were evaluated for exercise tolerance, indices of
      intracardiac hemodynamics, parameters characterizing the rheology-hemostasis
      system, those of immune reactivity and lipid spectrum. Comparative evaluation of
      results of rehabilitative treatment in the above patients and reference group did
      not reveal differences over the long-term follow-up, which fact may become a
      prerequsite for reconsideration of the temporary disability periods in these
      patients with cutting down those periods on the average by two weeks.

PMID- 9621638
TI  - [The functional characteristics of patients with the silent form of ischemic
      heart disease].
AB  - A total of 124 patients with ischemic heart disease (IHD) were studied. Of these,
      53 presented with painless IHD form, 28 patients had atypical pain syndrome. It
      has been shown that the threshold exercise level both in those persons free from
      angina pectoris but with postinfarction cardiosclerosis and those with no history
      of myocardial infarction is not significantly different from and is appreciably
      higher than in IHD patients with angina pectoris and episodes of "silent
      ischemia". Informative value has been studied of other diagnostic tests in the
      above patients: stress-test appeared to be positive in 42.8% of patients, cold
      test--in 6.3%, hyperventilation test in 16.8% of patients. Painless myocardial
      infarction (PMI) was detected in 50% of patients with postinfarction
      cardiosclerosis and 63.6% with no history of myocardial infarction, as evidenced
      by 24-h ECG monitoring. Analysis of angiogrammes in those persons with atypical
      pain syndrome showed hemodynamically significant injury to the coronary vessels
      in 57.1% of patients and a spasm of coronary vessels in 33.3%. PMI occurs in
      patients with different IHD forms including those with prior MI free from
      stenocardia.

PMID- 9621639
TI  - [The characteristics of the DIC syndrome in gastrointestinal hemorrhages].
AB  - With the purpose of assessing the part DIC syndrome has in hemorrhage, blood
      coagulation system was studied in patients presenting with gastrointestinal
      hemorrhage. Thrombin, a blood coagulation IIa factor, which is one of the chief
      markers of DIC syndrome, has been found in great amounts in blood in 50% of
      cases. But this did not lead to disseminated transformation of fibrinogen to
      fibrin because of the action of the inhibitor of coagulation during the stage of
      activation of fibrinogen by thrombin. Antithrombin III had but a minor part in
      these processes. It is suggested that rise in concentration of thrombin that is
      not accompanied by formation of disseminated fibrin might be of compensatory and
      adaptive significance. Another characteristic of blood coagulation system in the
      patients is depressed plasminolysis, while increase, against this background, in
      concentration of products of fibrin/fibrinogen degradation that is most common,
      reflects disturbance in the processes of their elimination from the bloodstream.

PMID- 9621640
TI  - [An assessment of the prognostic criteria for early recurrences of peptic
      hemorrhage].
AB  - The proposed prognostic system involves multivariate (step-by-step
      discriminatory) analysis allowing the risk for the coming early recurrent
      ulcerous bleedings to be assessed to an accuracy of 84%. Depending on the degree
      of the risk there have been identified three groups of patients: those of
      minimum, high and extremely high risk of recurrence of bleeding. The selection
      algorithm for time of surgical treatment of patients with acutely bleeding
      pyloroduodenal ulcers takes account of emergency operations (within 24 hours) for
      patients in the high and extremely high risk groups, allowing the specific weight
      of interventions at the height of the recurrent bleeding to be reduced from 31%
      to 14%.

PMID- 9621641
TI  - [Hormonal disorders in patients with chronic pyelonephritis with nephrosclerosis
      and kidney failure].
AB  - Blood plasma content was studied of hydrocortisone, parathyroid hormone (PTH) and
      calcitonin in patients with chronic pyelonephritis (ChP) using methods of
      radioimmunologic and immunoenzymatic analyses. ChP patients had marked
      alterations of blood plasma levels of hydrocortisone, PTH and calcytonin, with
      the reduced levels of hydrocortisone and hypercalcitoninamia being noted during
      the early stages of nephrosclerosis. It is suggested that hydrocortisone and
      calcitonin content in blood of ChP patients might be used as indicators of state
      of the endocrine mechanisms controlling the renal connective tissue metabolism
      during the early stages of nephrosclerosis. The above measure will also be
      helpful in the assessment of activity of the sclerotic process in the kidneys,
      prognosis of the outcome of the medical condition, and development of treatment
      options of adequate pathogenetic therapy.

PMID- 9621642
TI  - [Laser puncture diskectomy in discogenic lumbosacral radiculitis].
AB  - Percutaneous laser discectomy (PLD) was performed in 273 patients with herniated
      disc-induced lumbosacral radiculitis. Indications for PLD were based on clinical
      and neurological findings and results of MR tomography: no benefit from
      conservative treatment, pain syndrome in the lumbago stage and sciatica not
      presenting with severe paresis and with herniated intervertebral discs down to 6
      mm in size across.

PMID- 9621643
TI  - [The correction of the immune and microcirculatory disorders in patients with
      chronic hepatitis of alcoholic and viral etiologies].
AB  - 156 patients with chronic alcoholism revealed chronic liver lesions of alcoholic
      and viral genesis as evidenced by comprehensive clinical and laboratory
      evaluation. All examinees had significant immune and microhaemocirculatory
      disorders. Employment of antral in the complex therapy of 82 patients with
      chronic hepatitis (ChH) of viral and alcoholic genesis made for improvement of
      immunologic and microcirculatory indices, which fact permits recommending the
      drug in a complex of therapeutic measures to be instituted in ChH patients.

PMID- 9621644
TI  - [The correlation of the metabolic link of the activity of the endogenous opiate
      system in alcoholism].

PMID- 9621645
TI  - [The importance of taking personality characteristics into account in treating
      alcoholism].
AB  - As many as 268 individuals revealed signs of alcoholism. These persons suffered
      from accentuation of character or psychopathy. The treatment was carried out with
      different emotional and stress methods. Controls (n = 72) were treated without
      taking the patient's disposition into account, with remission for more than one
      year being in 7.3% of cases. The treatment in the main group (n = 100) was
      prescribed with taking the person's disposition into account. Epileptoid and
      emotionally liable individuals derived great benefit from the treatment modality
      "Esperal" (remission for more than one year in 37.4% and 31.3% respectively),
      hyperthymic, psychoasthenic and schizoid patients--from "Coding" (41%, 49.3%,
      39.4% respectively), hysteroid ones--from "Torpedo" (37.3%).

PMID- 9621646
TI  - [An epidemiological study of cerebro- and cardiovascular morbidity in the
      population of Kam'ianets'-Podil's'kyi].

PMID- 9621647
TI  - [The correction of the water-electrolyte balance and the acid-base status in a
      severe course of leptospirosis].
AB  - The clinical course of grave forms of leptospirosis presents with disorders in
      the fluid and electrolyte balance and acid-base condition (ABC) which fact
      necessitates taking prompt action for the condition to be corrected. Correction
      of disorders in the fluid and electrolyte balance involves employment of glucose
      and salt solutions, dextrans, and in most severe cases albumin drugs under
      control of hematocrit values, plasma osmolarity, and 24-h diuresis monitoring.
      Correction of disorders in the ABC is primarily aimed at alleviating the
      metabolic acidosis through detoxication by applying specific therapy together
      with oral and parenteral administration of sodium hydrogen carbonate.

PMID- 9621648
TI  - [The use of a hypertonic sodium chloride solution in combination with polyglucin
      in septic shock patients].
AB  - Efficacy was studied of combination of the sodium chloride hypertonic salt
      solution plus polyglukin in eight patients with burn shock. The above combination
      in the dose of 7.2 +/- 0.8 ml/kg of body mass was found out to make for
      stabilization of arterial blood pressure and obviate the necessity of employing
      infusion of dopamine, but cannot be regarded as a radical therapeutic
      alternative. The above treatment option can be recommended as a measure designed
      to be used for a short time only to maintain an adequate haemodynamics in this
      extremely grave condition.

PMID- 9621649
TI  - [The use of the new biological adhesive preparation fibrin polymer in thyroid
      surgery].
AB  - A study made in 18 patients with nodular euthyroiditis and toxic goiter proved
      high efficacy of a new preparation "Fibrin Polymer" ("Bioadhesive") based on a
      combined action of human fibrinogen and thrombin. Employment of the above
      preparation makes for maintaining intraoperative hemostasis, reducing
      postoperative wound serous and haemorrhagic and lymphatic secretion, joining lips
      of skin wound to improve cosmetic results of the operation. A novel modality is
      proposed for low-invasive treatment of cystic forms of nodular goiter based on
      obliteration of the cyst with the aid of the preparation "Fibrin Polymer"
      administered by puncturing the cyst following aspiration of its contents. Of the
      eight treated patients, 1 had a recurrence, 2 subjects had more than 2-fold
      diminution in cyst size, 5 patients recovered 12 months following the treatment.
      The preparation "Fibrin Polymer" should, we believe, come to be widely used in
      thyroid surgery.

PMID- 9621650
TI  - [Computed tomography in the diagnosis of digestive tract tumors].
AB  - As many as 616 patients with malignant tumours of the alimentary canal were
      studied by CT tomography using different contrast mediums and methodical
      approaches toward identifying the site of the tumour. Based on the comparison of
      the results obtained from pathomorphologic findings and those from the surgical
      intervention, CT semiotics has been developed of tumours, criteria established to
      determine the depth of the tumour invasion and extra-wall spread of the tumour CT
      potentialities were verified in the diagnosis of metastatic involvement of
      regional lymph nodes and remote organs as was the role of the method in selection
      of a specific therapeutic alternative.

PMID- 9621651
TI  - [Enhancing antitumor resistance during the treatment of patients with ovarian
      cancer].

PMID- 9621652
TI  - [The use of cryosurgery and electrodestruction of the endometrium in treating
      patients with hyperplastic processes in the uterus].
AB  - Based on the findings obtained a conclusion was reached that cryosurgery is a
      worth-while exercise in patients of child-bearing age as a method enabling the
      menstrual function to be preserved. Electrodestruction of endometrium is to be
      targeted to patients of perimenopausal age to achieve amenorrhea. The aim of the
      above policy of managing patients is to enhance efficacy of treatment of
      hyperplastic processes in endometrium.

PMID- 9621653
TI  - [The therapeutic and prophylactic anti-ulcerogenic action of marigold (Tagetes
      patula L.) and sea buckthorn (Hippophae) oils in neurogenic ulcerative lesions
      caused by immobilization, noise and vibration].

PMID- 9621654
TI  - [The use of mountain air therapy for the correction of acid formation in patients
      with hypo- and hyperacidic syndromes].
AB  - Changes were studied in intragastric pH with the aid of micromethods of topo-pH
      metry in 46 patients presenting with hypo- and hyperacidic syndrome exposed to
      artificial mountain air (AMA) therapy. The gas mixture containing 14% oxygen was
      formed by using molecular sieves. AMA was found out to have a significant
      sanogenic effect: it makes for acid production in patients with hypoacidic
      syndrome and reduces the above production in those patients presenting with
      hyperacidic syndrome AMA therapy administered along with the judicious employment
      of blockers, Hs-histamine receptors will, we believe, help in alleviating and
      dispelling the withdrawal syndrome.

PMID- 9621655
TI  - [Laser irradiation in the treatment of autoimmune thyropathies].

PMID- 9621656
TI  - [Facial nerve neuritis--the anatomicophysiological basis of acupuncture
      treatment].

PMID- 9621657
TI  - [The characteristics of the clinico-diagnostic and therapeutic treatment
      procedures for workers in the marine transport shore services who are ill with
      circulatory encephalopathy].
AB  - A distinguishing feature of the course of discirculatory encephalopathy (DE) in
      workers of seaborne transport (shore services) is a high degree of vegetative and
      emotional (during the early stages) and affective, psycho-organic (stage II-III)
      disturbances secondary to adverse effects of varying kinds of social and biologic
      factors. We undertook to develop a diagnostic algorithm and treatment options to
      deal with DE aggravation and complications. Combined use of physical factors,
      vegeto- and vasotropic drug preparations, antihomotoxic and metabolic
      alternatives make for regression of the process, its stabilization, with
      beneficial effect being exerted on the brain vascular formations reactivity and
      vegetative maintenance of functions in the sick.

PMID- 9621658
TI  - [Valneological centers: the prerequisite and need for their creation].

PMID- 9621660
TI  - [Semester exams in medical college: an academic necessity or a tribute to
      tradition?].

PMID- 9621659
TI  - [Syphilis morbidity in Ukraine in the 20th century (a review of the literature
      and the author's own data)].

PMID- 9621661
TI  - [Novel mechanisms for increasing Ca2+ sensitivity of contractile apparatus in
      smooth muscle].
AB  - Smooth muscle contraction is primarily regulated not only by changes in cytosolic
      Ca2+ concentrations ([Ca2+]i) but also by changes in the force/[Ca2+]i ratio. The
      use of membrane-permeabilization technique facilitated demonstration of an
      increase in the level of force at constant [Ca2+]i (Ca2+ sensitization). It was
      clarified that Rho-associated kinase (Rho-kinase) is a novel mediator of Ca2+
      sensitization of the smooth muscle contraction, by introducing the recombinant
      catalytic domain of Rho-kinase into the cytosol of vascular smooth muscle
      permeabilized with beta-escin. This review article focuses on novel mechanisms,
      by which activation of receptor-coupled G-protein(s) increases Ca2+ sensitivity
      of the contractile apparatus in smooth muscle: Rho-kinase and protein kinase C.

PMID- 9621662
TI  - [Effects of cardiopulmonary bypass on hepatic circulation and hepatic oxygen
      metabolism under fentanyl anesthesia in beagles].
AB  - Disturbances of hepatic blood flow (HBF) and hepatic oxygen metabolism (HMO) have
      been reported in patients and animals undergoing cardiopulmonary bypass (CPB). In
      the present study, we examined changes of HBF and HMO during CPB in eight beagles
      (13.5 +/- 2.4 kg). Hepatic arterial blood flow (HABF) and portal venous blood
      flow (PVBF) were measured with an electromagnetic flowmeter before CPB, during
      normothermic CPB, during hypothermic CPB under 10 micrograms.kg-1.h-1 of fentanyl
      anesthesia. CPB was conducted with membrane oxygenation and a non-pulsatile pump
      flow of 2.4 l.min-1.m-2. Hepatic oxygen delivery (HDO2) and consumption (HVO2)
      were calculated from HBF and oxygen content in arterial, portal venous and
      hepatic venous blood. Hepatic energy charge (HEC) was also assessed by measuring
      the arterial ketone body ratio (AKBR). HABF was unchanged during CPB, but PVBF
      decreased during normothermic CPB. Total hepatic blood flow decreased during
      normothermic and hypothermic CPB. HDO2 decreased during CPB because the oxygen
      content in the arterial and portal venous blood decreased. However, HVO2 was well
      maintained by spontaneous rises in oxygen uptake ratio despite the decrease in
      HDO2. The AKBR remained above 0.8 during CPB. Our results indicate that the CPB
      technique in the present study decreased HBF, but did not cause any adverse
      effects on HOM or HEC.

PMID- 9621663
TI  - [An experimental study on ischemically induced brain damage by whole body
      calorimetry and pathohistology in the gerbil].
AB  - Moderate hypothermia has been reported to mitigate neuronal damage in the gerbil
      brain following brief periods of forebrain ischemia, but the relationship between
      brain damage and whole body calorimetry has not been clarified. We report the
      effect of hypothermia on the brain damage by whole body calorimetry using Bio
      Dynamic Calorimeter (BDC200, ESCO Ltd JAPAN). Although it is an indirect method,
      whole body calorimetry may be able to measure the brain damage, thereby enabling
      investigations on alleviation of brain damage.

PMID- 9621664
TI  - [Anaphylactic shock associated with a central venous catheter impregnated with
      chlorhexidine and silver sulfadiazine].
AB  - A 28 year-old male patient developed anaphylactic shock on separate occasions,
      possibly due to the contact with a central venous catheter impregnated with
      chlorhexidine and silver sulfadiazine. He was successfully resuscitated. On the
      second operation, blood basophils disappeared and plasma histamine level
      increased extremely up to 80 ng.ml-1 soon after anaphylactic shock. One year
      after the first shock, he did not develop anaphylactic shock following the
      insertion of a central venous catheter without the impregnation. Pin prick test
      and scratch test showed positive reactions only to chlorhexidine. Latex-specific
      anti-IgE antibody was not detected. Therefore, chlorhexidine was confirmed as the
      causative agent of anaphylactic shock. Because chlorhexidine is extensively used
      as an antiseptic drug in emergency rooms and intensive care units, we should be
      aware of the possibility of chlorhexidine induced anaphylactic reactions.

PMID- 9621665
TI  - [The efficacy of low-dose propofol for intrathecal morphine-induced pruritus].
AB  - We investigated the efficacy and untoward effects of low doses of propofol for
      intrathecal morphine-induced pruritus. Twenty gynecological and obstetric
      surgical patients received spinal anesthesia with 0.5% tetracaine and
      phenylephrine, as well as 0.2 mg morphine. Seven of them (35%) complained
      pruritus graded according to the treatment necessary in the postoperative period.
      Propofol, 10 mg or 20 mg, successfully alleviated the pruritus in 6 patients out
      of 7. Further treatment was not necessary in 5 of them. One patient was resistant
      to treatments by 20 mg of propofol and 0.1 mg of naloxone. Three patients
      transiently fell in sleep even after administering 10 mg of propofol. The authors
      conclude that low dose propofol is effective in treating intrathecal morphine
      induced pruritus, although it may transiently causes hypnosis in postoperative
      patients.

PMID- 9621666
TI  - [Urgent cesarean section under combined spinal and epidural anesthesia in a
      patient with aortitis syndrome].
AB  - We report the anesthetic management of a patient with aortitis syndrome using
      combined spinal and epidural anesthesia. A 28-year-old gravida with aortitis
      syndrome accompanied by faints was scheduled for an urgent cesarean section.
      Combined spinal and epidural anesthesia was thought to be better for this case in
      order to monitor the cerebral circulation by her consciousness level and to
      reduce the hemodynamic change during surgery as compared to spinal or epidural
      anesthesia alone. After inserting an epidural catheter at the Th 12/L 1
      interspace, spinal anesthesia was performed with 1.5 ml of 0.3% dibucaine at the
      L 4/L 5 interspace. The level of analgesia was under L 1 with the pinprick method
      10 min after the spinal anesthesia. Next, 5 ml of 1.5% mepivacaine was injected
      through the epidural catheter. The level of analgesia reached to Th 6 without
      major hemodynamic changes. A healthy 2740 g infant was delivered and she had an
      uneventful recovery. We conclude that combined spinal and epidural anesthesia is
      useful in a patient with aortitis syndrome undergoing an urgent cesarean section
      in order to monitor the cerebral circulation by the consciousness level and to
      reduce the hemodynamic change.

PMID- 9621667
TI  - [Midazolam for anesthetic induction in neonates].
AB  - The purpose of this study is to evaluate the effects of midazolam on circulation,
      respiration, sedation, and liver function of the neonates. The study subjects are
      27 neonates (body weight 2.1 to 3.8 kg, gestational age at birth 34 to 41 weeks)
      who underwent surgery in neonatal period. Of 27, 13 patients received lidocaine
      (1.5 mg.kg-1) immediately before tracheal intubation (group L), and 14 had
      midazolam (0.1 mg.kg-1) with lidocaine (group ML). We compared the effects of
      midazolam in the presence of lidocaine on the following parameters: (1) the
      incidence of hypotension (systolic blood pressure < 50 mmHg) and bradycardia
      (heart rate < 100 beats.min-1), (2) the incidence of apnea and desaturation of
      oxygen (< 80%), (3) the degree of sedation, and (4) the serum levels of bilirubin
      and unbound bilirubin after surgery. In group L, there were hypotension (1/13)
      and desaturation (1/13). In group ML, there were desaturation (1/14) and post
      operative apnea (1/14). None in both groups developed bradycardia or intracranial
      hemorrhage. A single-dose of lidocaine induced sedation only in 4 neonates, while
      combination of midazolam and lidocaine in 11. None had elevation of either total
      or unbound bilirubin after surgery. In conclusion, the titrated dose of midazolam
      with lidocaine is useful for anesthetic induction of neonates, although cares
      should be taken on its adverse effects such as hypotension, desaturation, and
      post-operative apnea.

PMID- 9621668
TI  - [Isoflurane anesthesia with combined use of low dose fentanyl for open heart
      surgery].
AB  - The hemodynamic and respiratory effects of high dose fentanyl anesthesia and
      those of isoflurane anesthesia with combined use of low dose fentanyl were
      compared in 40 patients undergoing open heart surgery. Twenty patients (Group
      Fen) were anesthetized with high dose fentanyl (about 100 micrograms.kg-1), other
      twenty patients (Group Iso) were anesthetized with isoflurane (inhalation of 1.0
      2.0%) combined with low dose fentanyl (about 8 micrograms.kg-1). Between the two
      groups, there were no significant differences in HR, CI, SVI, MPAP, MRAP, PVRI,
      RVCWI, LVSWI, DO2I, SvO2, and P/F ratio. In group Iso, there were significant
      decreases in mean arterial pressure (MAP) and systemic vascular resistance index
      (SVRI) at the time of sternotomy and before the cardiopulmonary bypass. In group
      Fen, a significant increase in VO2I occurred at the time of sternotomy. In ICU,
      catecholamine concentrations were significantly lower, and the duration of its
      use was significantly shorter in group Iso. Group Iso required significantly less
      time to awakening and to extubating. Therefore, group Iso shortened the length of
      ICU stays. In conclusion, isoflurane with combined use of low dose fentanyl
      anesthesia is an acceptable method of anesthesia for open heart surgery.

PMID- 9621669
TI  - [Two cases of clipping surgery of cerebral aneurysm under profound hypothermia
      with closed-chest extracorporeal circulation].
AB  - A 68-year-old female and a 47-year-old male patients underwent clipping surgery
      for giant basilar arterial and thrombotic internal carotid arterial aneurysms
      respectively with closed-chest extracorporeal circulation (femoro-femoral
      bypass). Profound hypothermia and continuous infusion of thiamylal were used to
      prevent brain damage. Blood outflow via the femoral vein was sufficient to induce
      profound hypothermia down to 20 degrees C. Hemodynamics were controllable without
      catecholamines during closed-chest extracorporeal circulation. Preoperative
      symptoms significantly improved and no neurological complication was observed in
      either case postoperatively. Right femoral phlebothrombosis was, however,
      observed in one case. In conclusion, profound hypothermia with closed-chest
      extracorporeal circulation is a safe technique to reduce the complications
      induced by open-chest technique, but special attention should be given to
      postoperative phlebothrombosis.

PMID- 9621670
TI  - [A patient with drug abuse who developed multiple psychotic symptoms during
      sedation with propofol].
AB  - We report a patient with drug abuse who developed multiple psychotic symptoms
      including euphoria, excitement, hallucination and delirium during sedation with
      propofol under spinal anesthesia. A 37-year-old man who had abused
      methamphetamines, thinner, phychomimetics and alcohol for 20 years was scheduled
      for skin transplant as day-case surgery. He was treated with cholorpromazine,
      haloperidol and flunitrazepam just before the surgery. Sedation with propofol
      under spinal anesthesia was thought to be suitable in order to prevent psychotic
      symptoms. After spinal anesthesia, propofol 5 mg.kg-1.h-1 was administered
      intravenously as sedation. However, euphoria and excitement appeared 10 min after
      the start of infusion. He also demonstrated excitement, hallucination and
      delirium under propofol 6-8 mg.kg-1.h-1. His symptoms were suppressed by
      intravenous injection of haloperidol 5 mg. We speculate that propofol may produce
      psychotic symptoms when it is used in patients with a history of drug abuse.

PMID- 9621671
TI  - [Epidural hematoma associated with epidural catheterization in a cirrhotic
      patient].
AB  - We present a case of epidural hematoma in a liver cirrhosis patient with a
      depressed platelet count but normal prothrombin and activated thromboplastin
      times. A 60-year-old woman hospitalized with liver cirrhosis was referred to us
      for low back pain. She suffered the fracture of the body of the 12 th thoracic
      vertebra in a fall. Her platelet count was below normal ranges, but, other
      coagulation tests were within normal ranges. We inserted an 18-gauge epidural
      catheter at Th 12-L1 interspace. Twenty-one days later, paresis and hypesthesia
      in both legs, and a loss of sphincter function occurred. Magnetic resonance
      imaging revealed a posteriorly placed hematoma extending from Th 12 to L1.
      Considering the hemorrhagic tendency and hepatic insufficiency, we did not
      perform laminectomy. After 4 days, the patient's strength began to recover, and
      after 7 days paresis and hypesthesia improved. We should avoid performing
      epidural catheterization to improve chronic pain for a patient with liver
      cirrhosis if his or her platelet count is below 100,000.mm-3.

PMID- 9621672
TI  - [Anesthetic management for renal tumor extending to the inferior vena cava].
AB  - A 58 year-old woman underwent radical nephrectomy, thrombectomy and ileo-cecal
      resection for renal tumor with thrombus involving the inferior vena cava and
      ascending colon cancer. In a patient having tumor thrombus extending to the vena
      cava, recognition of the position of the thrombus is important for surgical and
      anesthetic management in pre- and intra-operative periods. Transesophageal
      echocardiography (TEE) enabled us to visualize the real-time movement and
      deformity of thrombus by surgical manipulation and compression during operation.
      TEE seemed also very useful not only in understanding the hemodynamics during
      operation but also in detecting the residual tumor and the blood flow in liver
      and the inferior vena cava after operation.

PMID- 9621673
TI  - [Spinal anesthesia in a patient with spina bifida occulta].
AB  - A 32-year-old woman with spina bifida occulta was scheduled for hemorroidectomy
      under spinal anesthesia. Preoperatively, computed tomography and magnetic
      resonance imaging (MRI) were performed. The MRI demonstrated the conus medul
      laris reaching the L 3 level and a lipoma connected with conus medullaris
      intrathecally. Spinal anesthesia was done successfully at the L 3-4 interspace
      using 0.3% dibucaine 1.2 ml with 5% glucose 0.8 ml. Postoperatively she showed no
      neurologic complications. With exact anatomical findings of MRI, spinal
      anesthesia can be safely performed for patients with spina bifida occulta.

PMID- 9621674
TI  - [Preventive effect of fluid warmer system on hypothermia induced by rapid
      intravenous infusion].
AB  - The changes in body temperature induced by rapid intravenous infusion of lactated
      Ringer solution and the effect of a fluid warmer system (HOT LINE, Level 1
      Technologies, Inc., Rockland, MD) were investigated in 35 patients undergoing
      cardiovascular surgery. The patients were divided into 5 groups by categories of
      the fluid temperature (-19 or -38 degrees C), infusion route (radial or right
      subclavian vein), and infusion rate of lactated Ringer solution (1000 or 250 ml
      for 30 min). Pulmonary arterial, esophageal, bladder, and forehead deep
      temperatures, which reflect core temperature, were significantly decreased by the
      rapid infusion of unwarmed solution (0.8-1.0 degree C, P < 0.05). In contrast,
      these temperatures were maintained in the warmed solution groups as well as in
      the group of slow infusion rate. With regard to the infusion route, there was no
      significant difference in the temperature between the radial vein and subclavian
      vein groups. Plantar deep temperature showed no significant change during this
      study. In conclusion, infusion of warmed solution using HOT LINE could prevent
      hypothermia induced by rapid intravenous infusion, and this effect is not greatly
      influenced by route of venous infusion.

PMID- 9621675
TI  - [General anesthesia in a patient with Cornelia de Lange syndrome with restricted
      opening of the mouth].
AB  - Patients with Cornelia de Lange syndrome have many anomalies including
      micrognathia with a small mouth, a high arched palate, and a short neck, which
      might make laryngoscopy for tracheal intubation difficult during induction of
      general anesthesia. General anesthesia was performed in a patient with Cornelia
      de Lange syndrome, and restricted opening of the mouth, which had not been
      reported previously, was found during laryngoscopy. The possible causes were
      thought to be temporo-mandibular joint disorders, contracture of the masseter
      muscle due to injury by self-destructive tendencies, or elogated coronoid
      process. The potential difficulty with laryngoscopy should be considered for
      tracheal intubation in a patient with Cornelia de Lange syndrome.

PMID- 9621676
TI  - [Bronchodilator aerosol propellant interferes with an photoacoustic
      spectrophotometer respiratory gas analyzer].
AB  - A patient with bronchial asthma was scheduled for an operation under nitrous
      oxide-isoflurane anesthesia. We monitored isoflurane concentrations continuously
      using an anesthetic gas analyzer (BK 1304). Upon puffing procaterol hydrochloride
      aerosol for 4 times, the analyzer showed a rapid increase in end-tidal isoflurane
      concentration. The BK 1304 uses infrared photoacoustic spectrophotometry and it
      is susceptible to interferences caused by Freon propellants in bronchodilator
      aerosols. We should take care in monitoring inhalational anesthetics when using
      aerosols containing Freon propellants.

PMID- 9621677
TI  - [Acute angle-closure glaucoma following surgery for oral cancer].
AB  - A 60-year-old woman who had undergone surgery of oral cancer under general
      anesthesia developed an attack of acute angle-closure glaucoma the next morning.
      Her intraocular pressure decreased immediately by adequate treatments including
      surgical procedures (laser iridotomy and trabeculectomy), and her symptom
      improved. It is considered that this event was induced by several factors such as
      atropine given before and during general anesthesia, perioperative hypertension
      and anatomical abnormalities. However the definite cause of this event is
      unclear. We conclude that it is difficult to predict a glaucoma attack following
      surgery under general anesthesia, but this complication is an important
      ophthalmologic emergency. Immediate diagnosis and appropriate treatment should be
      done to prevent the grave prognosis.

PMID- 9621678
TI  - [A novel compact digital amplifier to control a medical equipment (Graseby 3500
      pump) by Macintosh computer without external power supply].
AB  - Most medical equipments now incorporate a digital RS-232 C interface, which
      enables to log data and/or control equipments by computers. Although the standard
      voltage specification of RS-232 C is minimum +/- 3 volts, certain devices, such
      as Graseby syringe driven pump model 3500 (U.K.), need higher voltage than the
      standard to reduce the risk of electromagnetic interference. Since the output
      voltage of serial port of Macintosh (Apple Computer Inc.) computer and other
      portable computers is around +/- 5 volts, an additional voltage amplifier is
      necessary to control such external devices. A compact digital signal amplifier
      was developed by using a general RS-232 C driver IC (MAX 232 E, Maxim USA). Bulky
      external power supply could be eliminated, because power was obtained through
      digital signal lines themselves.

PMID- 9621679
TI  - [Continuous intra-arterial blood gas monitoring during bronchopulmonary lavage
      for pulmonary alveolar proteinosis].
AB  - We report a clinical experience of continuous intra-arterial blood gas monitoring
      (PARATREND 7:P 7) during bronchopulmonary lavage. A 47-year-old, 86-kg male was
      suffering from myelodysplastic syndrome associated with alveolar proteinosis.
      Bronchopulmonary lavage was scheduled to alleviate the symptom. P 7 and a
      continuous cardiac output monitor were used with an EKG monitor, a pulse
      oximeter, and a esophageal stethoscope. Anesthesia was maintained using
      sevoflurane and fentanyl. The patient's trachea was intubated with a double-lumen
      endobronchial tube (39-F Broncho-cath; Mallinckrodt, Ireland). After
      denitrogenation and degassing, warmed isotonic saline was infused into his left
      lung. The volume chosen was 2,200 ml which approximated the sum of the patient's
      functional residual capacity and tidal volume. The lowest point of PO2 appeared
      at the point 'degassed'. P 7 showed a consecutive rise of PO2 associated with
      infusion of large volume of saline. Although the response to change in PO2 of P 7
      is slower than pulse oximeter, frequent blood sampling can be avoided. We think
      that P 7 with pulse oximeter are useful for the safe management of pulmonary lung
      lavage.

PMID- 9621680
TI  - Size distributions of misrejoining DNA fragments in irradiated cells.
AB  - When ionizing radiation strikes a cell it induces DNA double strand breaks
      (DSBs). Subsequently, some of the DSBs misrejoin and thus cause alterations in
      the size distribution of the DNA fragments. We derive a system of non-linear
      integro-differential equations describing the misrejoining interactions of five
      classes of DNA fragments, including rings and various types of linear fragments.
      The fragment classes are represented by density functions; the shape of a density
      function determines the probability that a fragment has a particular size and the
      amplitude (integral) equals the expected number of such fragments per cell. The
      equations are solved: analytically for exponentially distributed initial fragment
      sizes (corresponding to high doses) and numerically for arbitrary initial
      conditions. Computed final fragment size distributions are applied to situations
      representative of flow karyotypes and pulsed-field gel assays. For human flow
      karyotypes, the model can be used to obtain misrejoining estimates at doses too
      high for conventional methods of data analysis. For pulsed-field gel assays in
      which human chromosomes are digested with restriction endonucleases to form 'cut
      somes' (restriction fragments), the model provides a means of misrejoining
      estimation when the cut-some sizes are non-random. The model suggests that if the
      cut-some size distribution for unirradiated cells is completely random,
      misrejoining of radiation-induced DSBs will not be detectable in the final size
      distribution.

PMID- 9621681
TI  - Analytical solutions to a tapering multicylinder somatic shunt cable model for
      passive neurones.
AB  - A multicylinder somatic shunt cable model for passive neurones is considered in
      which one or more tapering equivalent cylinders emanate from a uniformly
      polarized soma. Each tapering equivalent cylinder approximates the loss of
      dendritic trunk parameter in the one or more dendritic trees that it represents,
      relaxing certain symmetry conditions necessary for the Rall equivalent cylinder
      concept and in particular allowing terminal branches to end at different
      electrotonic lengths. The case of exponential taper is considered in detail
      following the anatomical data on apical and basilar dendrites of CA1 and CA3
      hippocampal pyramidal neurons obtained by Turner and Schwartzkroin [J.
      Neurophysiol. 44 (1980) 184; J. Neurosci. 3 (1983) 2381].

PMID- 9621682
TI  - A delay differential equations model of plankton allelopathy.
AB  - In this paper we have studied the dynamics of planktonic growth with special
      consideration on time dependent fluctuations in density of the species. We
      propose a modified delay differential equation model of the growth of two species
      of plankton having competitive and allelopathic effects on each other. The model
      system shows a stable limit cycle oscillation when the allelopathic effect is of
      a stimulatory nature.

PMID- 9621683
TI  - Jungles: a new solution to the host/parasite phylogeny reconciliation problem.
AB  - The problem of finding least-cost reconstructions of past host/parasite
      associations, given the phylogenetic histories of a set of host taxa and of their
      associated parasites, is known to be complex. I provide in this article a new
      method of implicitly listing all the potentially optimal solutions to the
      problem, by considering each hypothesised past association individually, in a
      structure I have termed a Jungle. These structures are demonstrated to enable
      fast acquisition of globally optimal solutions under general weighting schemes,
      including minimisation of total number of postulated events and maximization of
      postulated cospeciation events. A simple example is given, and the pocket
      gopher/chewing louse system investigated by Hafner and Nadler [Hafner and Nadler,
      Nature 332 (1988) 258] is re-examined.

PMID- 9621684
TI  - [A morphological and cytofluorometric analysis of the age structure of yeast
      populations].
AB  - The morphological and cytofluorometric analysis of the age structure of yeast
      populations of Saccharomyces cerevisiae, Candida boidinii and Candida tropicalis
      were carried out. The phase of cell preparation for budding and three phases of
      budding were accounted in morphological analysis. The latter was determined by
      the ratio of size of a mother cell and a bud. Cytofluorometric analysis was
      carried out by flow cytofluorometry of 20,000 cell which were stained by ethidium
      bromide. A simple method to determine the share of yeast cells in different
      phases of the cell cycle was proposed. The data obtained by cytofluorometry and
      by morphological analysis of population's age structure correlate between
      themselves.

PMID- 9621685
TI  - [A comparison of the developmental characteristics of Neisseria gonorrhoeae and
      Staphylococcus aureus cultures on nutrient media of different compositions].
AB  - The growth parameters of gonococcus and staphylococcus strains in liquid medium
      were determined. The generation time varied within the limits from 0.8 to 1.3 h
      for gonococcus and from 0.47 to 0.60 h for staphylococcus, the specific growth
      rate varied from 0.51 to 0.91 h-1 for gonococcus and from 1.68 to 2.11 h-1 for
      staphylococcus, depending on the concentration of sodium humate and bovine serum
      in the medium. The growth characteristics of analysed staphylococcus strains did
      not depend on the presence of plasmids. The gonococcal cultures grown in the
      liquid nutrient medium containing 20% of bovine serum for 8-11 h were the most
      physiologically active. Sodium humate added to the medium for cultivation in
      concentration 0.01% stimulated the growth of N. gonorrhoeae.

PMID- 9621686
TI  - [The sensitivity to landomycins A and E of streptomycetes, producers of
      polyketide antibiotics].
AB  - Streptomycetes, which are the producers of different polyketide antibiotics, can
      be divided into 4 groups as to their sensitivity to landomycins A and E: 1) S.
      glaucescens Tu49, producer of tetracenomycin and S. aureofaciens 019, producer of
      chlortetracycline belong to the most landomycin-sensitive strains. 2) S.
      cyanogenus S136, producer of landomycin A, and S. lividans TK24, producer of
      actinorhodin, were sensitive to mean and high doses of landomycin E (more than 60
      80 ug/ml). 3) S. globisporus 1912 (producer of landomycin E), S. cyanogenus S136,
      S. fradiae Tu2717, producer of urdamycins and S. coelicolor A3(2), producer of
      actinorhodin have moderate sensitivity to all doses of the both antibiotics but
      strain S136 only to low doses. 4) Resistance to landomycins A and E was observed
      in strain S. olivaceus Tu2353, producer of elloramycin. In all the experiments
      landomycin E showed the 1-2 orders higher lethal activity in comparison with
      landomycin A which molecule is composed of the same aglycon landomycenone A but a
      longer polysaccharide chain which probably hampers the penetration of antibiotic
      through the cell membrane.

PMID- 9621687
TI  - Influence of Bacillus subtilis sp. lectin on functional activity of phagocytes.
AB  - Intramuscular and intraperitoneal introduction of Bacillus subtilis sp. lectin to
      mongrel white mice is responsible for the increasing of values of functional
      activity of peripheral blood phagocytes and peritoneal macrophages of these
      animals. These results confirmed similar data obtained in vitro. Bactericidal
      activity of monocytes and neutrophils significantly increased at minimal doses of
      lectin (0.1-0.5 microgram/animal). But this increase was lower at middle doses
      (0.5-5.0 micrograms/animal) and again increased at higher ones (5.0-25.0
      micrograms/animal). Dose-dependent effect of lectin on macrophages was similar,
      but it was observed at lower concentrations. Administration of lectin did not
      give increase of functional reserve of studied cells, but was responsible for the
      increase of the phagocyte number and phagocytic index of monocytes and
      neutrophils at relatively middle doses (1.0-5.0 micrograms/animal). Phagocytic
      activity of macrophages did not increase. Thus, lectin of B. subtilis sp. is the
      agent non-toxic during studies in vivo, stimulating functional activity of
      phagocytes and macrophages.

PMID- 9621688
TI  - [The safety and reactogenicity of the new probiotic subalin for volunteers].
AB  - Data are presented on the study of innocuousness and reactogenicity of a new
      recombinant probiotic subalin characterized by antibacterial and antiviral
      activity. Volunteers who took subalin (one dose twice a day for 10 days) were
      under observation at Kyiv Scientific-Research Institute of Epidemiology and
      Infectious Diseases of the Ministry of Public Health of Ukraine. They carried out
      clinical and bacteriological investigations during administration and after
      termination of the course of oral administration of subalin testified to its
      innocuousness as well as to the absence of any side-effects.

PMID- 9621689
TI  - [The collective immunity of the population of the city of Kyiv and Kyiv Province
      to poliomyelitis].
AB  - The state of collective immunity to poliomyelitis has been studied for the
      population of the city of Kyiv and Kyiv Province. Insufficient safeguard of the
      examined quota from this infection has been shown. Special anxiety is caused by
      low indices of immunity to type III poliovirus. The expediency of revaccination
      of adult population is indicated.

PMID- 9621690
TI  - [A toxicological hygiene assessment of microorganisms likely for the creation of
      agents for agricultural intensification].
AB  - Pathogenic properties of new technological bacterial and fungal strains have been
      studied in rats, mice and guinea pigs. Products of these strains were planned to
      be implemented in agriculture (pesticides, growth regulators, etc.) Various
      protocols of toxicological studies of strains and microbial preparations have
      been used including sensibilization, immunomodulation and disbiotic testing. The
      objects studied, were classified as nontoxic and non-infecting for mammals. They
      may be implemented in the agriculture and microbiological industry with the
      application of routine sanitary standards.

PMID- 9621691
TI  - [The development of a method for viral inactivation using thiophosphamide].
AB  - Using three-functional alkylating compound thiophosphamide complete inactivation
      of the influenza and herpesviruses of type 1 and 2 was achieved. The method
      provides full inactivation of DNA- and RNA-containing viruses and preservation of
      their immunogenic properties.

PMID- 9621692
TI  - Construction of phylogenetic tree based on G + C contents in DNA and 16S rRNA
      sequences: example for group 1 of genus Bacillus.
AB  - The applicability of the G + C content in DNA in the construction of phylogenetic
      tree was studied. The group 1 of the genus Bacillus was selected as an object for
      study. Statistically reliable correlation between evolutionary distances of 16S
      rRNA sequences (Ei) and parameter Pi named as "GC evolutionary distance" was
      shown. The value of Pi is the difference between the G + C content in DNA of two
      species branching from one phylogenetic line. The coefficient of correlation
      between Ei and Pi equals 0.97 for the representatives of group 1, including
      Bacillus anthracis, B. cereus, B. circulans, B. firmus, B. lautus, and B.
      subtilis. Phylogenetic studies of the G + C content in DNA in the genus Bacillus,
      group 1 representatives has shown that this character can be used in molecular
      systematics and phylogeny as additional data altogether with the data on 16S rRNA
      sequences.

PMID- 9621693
TI  - [Nitazole--an antimicrobial substance].
AB  - The antibacterial activity of protistocide drug nitazole has been revealed for
      the first time in the 80's at the Laboratory of Clinical Microbiology of the
      Mechnikov Research Institute of Microbiology and Immunology. Unlike other
      imidazoles, such as metronidazole and tinidazole, nitazole acts as the inhibitor
      of growth of gram-positive facultative and obligate anaerobic microorganisms as
      well as gram-negatives except for Pseudomonas aeruginosa and Proteus. Nitazole,
      as a main antimicrobial agent of many multicomponent drugs which are created on
      the hydrophilic basis (matrices), is particularly useful for topical treatment of
      wounds and burns in the first and second phases of these processes. Drugs which
      include nitazole possess not only antibacterial and protistocide activity but
      also act as anti-inflammatory, wound-healing ones and have osmotic property.
      These drugs are approved by the Ukrainian Ministry of Public Health for wide use
      in surgical, gynecological, proctological and dermatological clinics as well as
      in combustology.

PMID- 9621694
TI  - [L. S. Tsenkovskii--the founder of the Ukrainian school of microbiologists].

PMID- 9621695
TI  - [Recent progress in the treatment of hepatolithiasis].

PMID- 9621697
TI  - [Cystic vein: as a perfusion vein of hepatic portion-angiographical study].
AB  - In order to determine the hepatic portions by cystic vein, we carried out
      abdominal angiography in 153 patients. The cystic vein was recognized in eleven
      patients, but only in nine cystic venous flow could be measured. In this group of
      patients, in which the cystic venous flow was detected, hepatic angiography was
      performed through the right hepatic artery (RHA) in six patients, the anterior
      branch of RHA in one patient, and the cystic artery in two patients.
      Simultaneously, angiographical CT was performed in five patients. As the results,
      it is presumed that the cystic venous flow perfused segment 4 portal branch (P4)
      + segment 5 (S5) in four patients, P4 in two patients, segment 6 portal branch
      (P6), S5 + right portal vein (RPV) + right hepatic vein (RHV), and S5 + RHV in
      one patient, respectively, and we concluded that in 70% of cases cystic venous
      flow perfused either P4 or S5.

PMID- 9621698
TI  - [Diagnosis of the wall-thickened lesions of the gallbladder with dynamic MRI].
AB  - We studied 32 patients with the thickened lesions of the wall of the gallbladder
      by using dynamic MRI. We tried the differential diagnosis of gallbladder lesions
      according to the time intensity curve (TIC) and enhanced pattern. TIC of
      carcinoma was elevated more seeply from plain to arterial phase than the
      inflammatory diseases. The Inflammatory diseases were keeping three-layer
      structures of the wall of the gallbladder, but gallbladder carcinoma destroys the
      wall-structure. We could diagnose as direct liver invasion of the carcinoma
      clearly. We could exactly diagnose adenomyomatosis in dynamic MRI by small low
      intensity spots within the wall of the gallbladder. In the patients with gall
      stones, the wall of the gallbladder were more clearly observed in dynamic MRI
      compared with US and EUS.

PMID- 9621699
TI  - [A case of the phlegmonous gastritis successfully treated by conservative
      therapy].

PMID- 9621700
TI  - [A case report of Cowden's disease with squamous cell carcinoma in papillomatous
      tonsil].

PMID- 9621701
TI  - [A case report of jejunal carcinoma in a patient with tuberous sclerosis].

PMID- 9621702
TI  - [A case of Wilson's disease associated with hypoparathyroidism and amenorrhea].

PMID- 9621703
TI  - [A case of hemorrhage into the gallbladder probably due to rupture of
      pseudoaneurysm formed by cystic artery].

PMID- 9621705
TI  - [Changes in serum anti-Helicobacter pylori IgG antibody, pepsinogen I, pepsinogen
      II after eradication therapy of Helicobacter pylori].

PMID- 9621704
TI  - [Serous cystadenoma of the pancreas with hypoplasia of the dorsal pancreas:
      report of a case].

PMID- 9621708
TI  - Test of the hopelessness theory of depression: drawing negative inference from
      negative life events.
AB  - The hopelessness theory of depression, i.e., that drawing negative inference from
      the occurrence of negative life events culminates in depression, was examined. A
      total of 34 dysphoric and 36 nondepressed undergraduate students participated in
      a two-stage prospective study lasting three months. The subjects completed the
      Beck Depression Inventory and Hopelessness Scale at both sessions and the Life
      Events Experience List at the second session. It is concluded that the inference
      of negative characteristics about the self from negative life events, coupled
      with the experience of negative life events contributes to the development of
      depression through hopelessness. The findings are discussed in relation to the
      Abramson, et al. hopelessness model of depression.

PMID- 9621709
TI  - Correlates of battered women's psychological distress: severity of abuse and
      duration of the postabuse period.
AB  - Although psychological disturbances among abused women are well documented, it is
      unclear whether such disturbances are a reaction to the abusive experience. The
      present study hypothesized that, if the disturbances are a reactive state, the
      severity of disturbance would be related to the time since the relationship ended
      as well as the severity of the psychological and physical abuse experienced.
      Participants were 50 abused women who completed valid MMPI-2s and revised
      Conflict Tactic Scales. The results indicated that MMPI-2 scores were
      significantly correlated with both types of abuse but not with duration of time
      since the abusive relationship was terminated. The MMPI-2 profiles of abused
      women and suggestions for research are discussed.

PMID- 9621710
TI  - Frequency of parental report of problem behavior in children decreases with
      increasing maternal age at delivery.
AB  - Child behavior problems were assessed in 1377 3-yr.-old twin pairs with the Child
      Behavior Check List from Achenbach (translated into Dutch language by Verhulst).
      The association between problem scores and maternal age at delivery of the twins
      was analyzed with statistical control for several potential confounding
      variables: birth weight of twins, maternal smoking during pregnancy, being breast
      or bottle fed and socioeconomic status. After controlling for all available
      confounding covariates, a significant linear effect for maternal age was left.
      Especially Externalizing behavior problems as well as the separate categories
      that constitute Externalizing, i.e., Aggressive, Oppositional, and Overactive,
      appeared to decrease continuously with increasing maternal age. This was true for
      both boys and girls as well as for first and secondborn twins. Evidence in
      support of a biological explanation of the association between maternal age and
      child behavior problems, is presented.

PMID- 9621711
TI  - Use of progressive relaxation training for chronic alcoholics with insomnia.
AB  - To assess the effect of progressive relaxation training on insomnia in
      institutionalised chronic alcoholic men, 22 subjects between the ages of 20 and
      60 years, were randomly allocated to treatment and control groups. The treatment
      group received 10 sessions of progressive relaxation training over a 2-wk. period
      after which both groups completed a postexperimental questionnaire. Analysis
      showed a significant improvement in the sleeping patterns of the treated group,
      but no changes in the sleeping patterns of the control group. In addition, a
      distribution-free two-sample permutation test to compare mean differences of the
      groups confirmed that a significantly greater change occurred in the quality of
      the sleeping patterns of the treated group.

PMID- 9621712
TI  - Satisfaction with relief agencies during Hurricanes Erin and Opal.
AB  - From a larger study, ratings of satisfaction with disaster relief agencies in the
      aftermath of Hurricanes Erin and Opal showed high satisfaction from services
      provided by the American Red Cross/Salvation Army and somewhat lower ratings for
      the Federal Emergency Management Agency from 167 residents and business owners in
      the Florida Panhandle.

PMID- 9621713
TI  - A preliminary study of coping styles of applicants for counselor education and
      their relations to admission criteria.
AB  - Responses of 100 applicants to a counselor education program were analyzed for
      their coping styles and the relations of these coping styles to a set of
      sociodemographic, academic, and experiential variables obtained during the
      application process. Seven factor-analytically derived coping styles are
      described. No significant relationships were found between these coping styles
      and the remaining variables.

PMID- 9621714
TI  - Breakfast consumption and intelligence in elderly persons.
AB  - The relationship between breakfast cereal consumption and intelligence was
      examined in a sample of 205 adults aged between 60 and 79 years. Those who
      consumed breakfast cereal every day had a higher mean score (38.4) on the
      National Adult Reading Test, known to correlate highly with intelligence, than
      that (M = 34.7) for the irregular breakfast eaters (WAIS predicted IQs for
      breakfast cereal everyday 118 and for irregular breakfast eaters 115).

PMID- 9621715
TI  - Severity of symptoms of depression and anxiety as predictors of duration of
      psychotherapy.
AB  - The present study explored predictors of the duration of therapy exclusive of
      outcome utilizing data on 77 patients at St. John's University Center for
      Psychological Services. Measures of time in therapy were the total number of
      sessions attended and the number of sessions attended within the first six months
      of therapy. A bivariate Pearson product-moment correlation matrix was
      constructed, comprised of measures for time in therapy, severity of symptom
      measures, treatment modality (psychodynamic or cognitive-behavioral), age, and
      sex. There was a significant correlation between scores on state anxiety and the
      total number of sessions as well as between scores on state anxiety and number of
      sessions attended within six months, but no other correlations between measures
      of severity of symptoms and time in therapy were significant (p > .05). The
      results indicate that severity of symptoms does not significantly predict the
      duration of therapy.

PMID- 9621716
TI  - Helplessness and depression.
AB  - In a sample of 45 undergraduates, depression scores were strongly associated with
      feelings of helplessness.

PMID- 9621717
TI  - Gender differences in love, sex, and motivation for sex.
AB  - In 1989 Sprague and Quadagno reported a significant interaction between sex and
      age for "motive for sexual intercourse" (affection-closeness vs physical
      release). Young men exceeded women in physical release as primary motive for sex,
      but women exceeded men in this choice at an older age. We conducted a modified
      replication, and we also studied Rubin's Love Scale, sexual interest, frequency
      of sexual arousal, and sexual enjoyment. Analysis did not confirm the earlier
      findings. For 60 men and 60 women differences were found for sexual interest,
      frequency of sexual arousal, and sexual enjoyment, with men scoring higher.
      Scores on Rubin's Love Scale did not differentiate the sexes.

PMID- 9621718
TI  - Comparison of alternative treatment techniques in bulimia: the chemical
      dependency approach.
AB  - Bulimia and chemical dependency are thought to be mediated by the nucleus
      accumbens, the primary pleasure center in the brain. These disorders consequently
      share biological, behavioral, and demographic characteristics. Also, earlier
      researchers have reported similar responses to different types of pharmacological
      intervention. There has, however, been little investigation of comparative
      nonpharmacological treatment modalities. The authors treated 10 white bulimic
      females in an eating-disorders program and a similar group in a 12-step chemical
      dependency center. Outcomes were similar for the weight-management program and
      for scores on the Brief Psychiatric Rating Scale. Implications are discussed.

PMID- 9621719
TI  - Primary therapists' views of managed care.
AB  - To assess the system's comprehensiveness in provision of public managed mental
      health care South Beach Psychiatric Center surveyed a sample (n = 54) of its
      primary therapists employed in its outpatient departments which have recently
      been reconfigured as key components of the New York State Office of Mental Health
      Prepaid Mental Health Plan. They are intended to be comprehensive resource and
      treatment centers which optimize recovery in a deregulated, capitated
      environment. As key informants, the primary therapists were asked to rate the
      difficulty they experience in providing or arranging adequate services and
      support groups in 19 areas. They were also asked to indicate if the fundamental
      problem was one of access, information, quality, or supply. The five areas with
      the highest ratings of difficulty were housing or residential services, substance
      abuse services, dental care, general health care, and employment or vocational
      services. The reason for difficulty most endorsed for these areas was supply. It
      is suggested that capitated managed care contracts can create incentives to
      increase the supply of such services.

PMID- 9621720
TI  - Body elimination attitude and occupation.
AB  - 16 food service personnel and 20 bank employees scored significantly higher
      (indicating greater disgust) on the Templer, King, Brooner, and Corgiat 1984 Body
      Elimination Attitude Scale than 46 nursing personnel and 15 sewage workers.

PMID- 9621721
TI  - College students' distorted perception of the prevalence of smoking.
AB  - Estimations of the prevalence of daily smoking of cigarettes by men and women on
      a college campus were obtained from 775 college students. Estimations greatly
      exceeded the percent of students who personally reported smoking cigarettes
      daily.

PMID- 9621722
TI  - Dependence on computer games by adolescents.
AB  - As computer game playing is a popular activity among adolescents, a questionnaire
      study was undertaken with 387 adolescents (12-16 years of age) to establish their
      "dependence" using a scale adapted from the DSM-III-R criteria for pathological
      gambling. Analysis indicated that one in five adolescents were currently
      "dependent" upon computer games. Boys played significantly more regularly than
      girls and were more likely to be classified as "dependent." The earlier children
      began playing computer games it appeared the more likely they were to be playing
      at "dependent" levels. These and other results are discussed in relation to
      research on other gaming dependencies.

PMID- 9621723
TI  - Out-of-body experience and personality functioning.
AB  - Reporters of out-of-body experiences (n = 21) and nonreporters (n = 159) showed
      no significant differences on the Spheres of Control Scale, Self-efficacy Scale,
      and Purpose in Life Scale. However, reporters of out-of-body experiences showed
      significantly greater belief in Psi, Spiritualism, and Extraordinary Life Forms
      than nonreporters.

PMID- 9621724
TI  - 7-year (circaseptennian) patterns in psychology and biology? Comment on Verhulst
      and Onghena.
AB  - Nonlinear rhythmometry confirms a pattern of about 7 years, describing the number
      of births by birth year of quantum fathers reported by Verhulst and Onghena in
      1996 and estimates the period to be 6.53 years with a 95% confidence interval
      overlapping 7 years. Other patterns of about 7 years are found in biology, as
      shown herein for the mean gonadal weight of an echinoderm (the purple sea urchin)
      and a mollusk (the black chiton). A number of periodic components with different
      frequencies, some shown to be genetically anchored, await applications in
      psychology as well as in other fields of medicine and biology.

PMID- 9621725
TI  - Self-defeating personality and social intimacy.
AB  - The Self-defeating Personality Scale and a modified version of the Miller Social
      Intimacy Scale were given to 98 men (M(age) = 40.3) and 104 (M(age) = 40.0) women
      to validate criterion seven (rejects people who consistently treat him/her well)
      of the former. Both the correlation between the full scale scores and those for
      the Miller scale and the correlation between Miller scores and scores on
      criterion seven of the Self-defeating Scale were nonsignificant. Cronbach alpha
      was .51.

PMID- 9621726
TI  - Modus operandi of female serial killers.
AB  - The modus operandi of female serial killers was examined from a chronology of 58
      cases in America and 47 cases in 17 other countries, compiled over 25-year
      intervals. Female serial killers in other countries accounted for a
      disproportionately greater number of victims, but those in America managed a
      longer killing career when associated with a low profile modus operandi.

PMID- 9621727
TI  - MMPI diagnostic classification of substance abusers of the 1970s.
AB  - Retrospective analysis of the MMPI profiles of 160 substance abusers tested in
      the 1970s showed that 54% were classified as showing signs of characterological
      disorder, 32% thinking disturbance, and 9% emotional disturbance. Four percent of
      the profiles were asymptomatic. These findings are presented both to confirm the
      wider variety of psychopathology in substance abusers of the 1970s than earlier
      and to provide current researchers with comparative data.

PMID- 9621728
TI  - Reports of husband battering from an undergraduate sample in Umtata.
AB  - The objective of the present study was to explore the extent to which husband
      battering is practised among Xhosa-speaking women (n = 138) and men (n = 81) in
      Transkei. Analysis showed that husband battering is not an unknown sociological
      practice as a small number of women do in fact beat up their husbands. Contrary
      to conventional and cultural knowledge wife battering is not a one-way phenomenon
      although it is practised more widely.

PMID- 9621729
TI  - Personality profiles of male and female positive role models in medicine.
AB  - This study was designed to investigate the personality profile of positive role
      models in medicine. Participants were a national sample of 188 physicians (164
      men, 24 women) who had been nominated by the chief executive officers of their
      institutions as positive role models and who completed the Revised NEO
      Personality Inventory. Compared to the general population, these 188 male and
      female positive role models in medicine scored higher on Conscientious factor,
      and on Achievement Striving, Activity, Competence, Dutifulness, Trust,
      Assertiveness, and Altruism facets, but they scored lower on the Vulnerability
      facet than the general population. In addition, the male role models scored
      significantly higher than men in the general population on the Agreeableness
      factor, and the female role models obtained significantly higher scores than the
      population norms on Extraversion and Openness factors, and on Feelings, Ideas,
      Positive Emotions, Values, Warmth, Aesthetics, and Fantasy facets. The female
      role models scored far below their sex-related norms on Neuroticism factor and on
      Angry Hostility facet. Comparisons between the male and female role models showed
      that the female role models scored higher on the Openness factor, and on the
      Feelings, Positive Emotions, Aesthetics, and Fantasy facets of personality.
      Implications in medical education and in explaining, assessing, and improving the
      qualities that contribute to professional success and in promoting the concept of
      "positive medicine" are discussed.

PMID- 9621730
TI  - Clients' positive and negative expressiveness within their families and
      alexithymia.
AB  - 49 prospective clients from a midwestern urban community, who sought counseling
      at a university training clinic, completed the Self-expressiveness in the Family
      Questionnaire and the 20-item Toronto Alexithymia Scale. As predicted, the
      positive self-expressiveness scores were significantly negatively correlated -.52
      with scores on alexithymia, and the negative self-expressiveness scores were
      significantly positively correlated .34 with alexithymia. These results support
      the premise that mental health clients' self-reported lack of positive
      expressiveness and abundance of negative expressiveness within their family
      context may be attributes associated with their tendency to be alexithymic.

PMID- 9621731
TI  - Students in compensatory education programs: analysis of scores on performance
      assessments for the Iowa Test of Basic Skills.
AB  - Analysis of Mathematics and Language Arts scores for 11,438 fourth- and 8,972
      seventh-grade students in compensatory education programs on the performance
      assessments for the Iowa Test of Basic Skills indicated the students performed
      poorly, particularly in mathematics.

PMID- 9621732
TI  - Therapists' self-reported training and success rates in treating clients with
      childhood sexual abuse.
AB  - In this two-part study, three groups of therapists (16 psychologists, 11
      counselors, and 14 social workers) were compared with regard to their success
      rates with clients presenting with childhood sexual abuse, and 43 graduate
      programs were asked whether they offered courses covering counseling techniques
      with such clients. Therapists' self-reported success rates were not significantly
      related to therapists' training, but type of therapy was. Given a response rate
      of 18.6%, self-reports should be treated cautiously. Over two-thirds of the
      training programs (45% response rate) offered courses covering issues in
      childhood sexual abuse and 67% offered courses covering counseling techniques
      with such clients. However, in 85% of these courses, treatment of childhood
      sexual abuse was a topic covered under more general course headings.

PMID- 9621733
TI  - Apprehension about communication and human resilience.
AB  - This study examined the relationship between scores on two personality
      characteristics, apprehension about communication and resilience, from 200
      elementary school teachers from several counties who completed the Personal
      Report of Communication Apprehension and the Personal Resilience Questionnaire.
      Scores on the two measures correlated -.33, which accounts for 10% of the common
      variance.

PMID- 9621734
TI  - GUTI: a measure of urgent task involvement among adults with attention-deficit
      hyperactivity disorder.
AB  - Attention-deficit hyperactivity disorder (ADHD) has been proposed to represent
      adaptive responding to highly urgent situations as in primitive hunting. In the
      present study, 31 adults with self-reported ADHD were compared with 33 normal
      adults on a newly developed, 10-item measure of urgent task involvement. The
      internal consistency of the scale was suitable, and the group with ADHD scored
      significantly higher than the control group, as predicted. Validation and further
      development of this scale is required for it to become a tool for the study of
      performance of highly urgent tasks.

PMID- 9621735
TI  - Role dimensions of patient and physician in medical interviews: relationship to
      patients' satisfaction.
AB  - We applied the Verbal Response Mode coding system to 80 medical interviews to
      characterize role dimensions of patient and physician and to assess the relation
      between physicians' role dimensions and patients' satisfaction. Role dimensions
      conformed closely to prior work. Physicians' acquiescence was positively
      correlated with satisfaction. This study suggests that the role dimensions
      generated by the Verbal Response Mode taxonomy are a useful measure of patients'
      and physicians' relationships.

PMID- 9621736
TI  - Control of understanding in a task involving medical assistance given by
      telephone.
AB  - This paper addresses the control of understanding in a task involving medical
      assistance given by phone. This situation was described and analyzed in two
      previous papers with different goals. Here we focus on activity carried out by
      the operator in charge of emergency calls (injuries, suicides, medical
      problems,...) in which the operator must control data given by the caller. We
      assume that the quality of data in the very first message (by the caller)
      influences the nature of control (by the operator). Methodology for assessing
      quality of information and type of control is presented. Nature of control is
      categorized by "validation" or "checking." Quality of information is assessed by
      an "informational rate" and some actual verbal exchanges illustrate this point.
      Findings show that control in the course of dialogues is determined by the
      quality of information sent by the caller initially.

PMID- 9621737
TI  - Lethal vs nonlethal suicide attempts in jail.
AB  - The rate of suicide in jails has been found to be 11 to 14 times greater than
      suicide within the general population. The purpose of the present study is to
      compare the demographic, offense, and situational characteristics of 665 adult
      male and 89 female jail inmates who attempted suicide by either hanging (lethal)
      or wrist or arm-cutting (nonlethal). Hanging attempts occurred at twice the rate
      of cutting attempts. Further, the mortality rate of inmates' attempts by hanging
      (52 deaths in 602 attempts) was 19 times greater than inmates who cut themselves
      (1 death in 275 attempts). Of all hanging suicide deaths 63% occurred on the
      inmate's first day of jail. The inmate's race, condition at arrest, hours after
      booking, type of charge, and size of jail differentiated lethal from nonlethal
      suicide attempts. Implications of these data for assessment of jail suicide risk
      and prevention are discussed.

PMID- 9621738
TI  - Using "stages of behavioral change" constructs to measure the short-term effects
      of a worksite-based intervention to increase moderate physical activity.
AB  - We evaluated a three-level incentive program to promote regular, moderate
      physical activity among employees working in a federal agency. The objective was
      to assess the short-term effects of the intervention by examining the stages
      people go through as they attempt to make permanent changes in physical activity.
      Indicators of the process by which changes in physical activity take place were
      based on a modified version of the Transtheoretical Model of Behavior. A one
      group pretest/posttest design was used to ascertain which of the stages the 1,192
      participants were in both before and after the intervention. Analysis indicated
      that, of the 1,192 participants, 6.5% regressed one or more stages, 30.3% did not
      regress or progress from one stage to another, 27.7% remained in the maintenance
      stage, and 35.4% progressed one (21.1%) or more (14.3%) stages during the 50-day
      intervention. Among those who progressed, the most common change was from
      preparation to late preparation (20.8%) and from late preparation to action
      (19.4%). Findings reinforce the notion that the stages of change concept can
      serve as indicators of the change process which in turn, can be used as evidence
      of the short-term effectiveness of interventions. Findings also indicate this
      type of intervention holds promise for increasing physical activity among willing
      participants of a worksite population.

PMID- 9621739
TI  - An undergraduate course on adult development, aging, and diversity.
AB  - The authors designed an activity-based general education course on adult
      development, aging, and diversity. Elements of diversity addressed in the course
      included ethnicity, race, sex, cohort, religion, and place of residence. 47
      students' favorable evaluations suggested such a course may be useful.

PMID- 9621740
TI  - Anxiety and burnout in the health care work environment.
AB  - Burnout is linked to many problems of employees and to organizational
      effectiveness. Using the Maslach Burnout Inventory and the State-Trait Anxiety
      Inventory, this study considered the effects of the trait (a personality
      characteristic), and the state (a response to stressful stimuli) of anxiety to
      perceived burnout. Analysis showed that scores on both trait and state anxiety
      were significantly related to scores on burnout. Moderators, including
      characteristics of the work environment, as measured by selected subscales of the
      Work Environment Scale were evaluated for their influence on the anxiety-burnout
      linkage. Peer and supervisory support, age, and prior knowledge of work-day
      situations moderated anxiety about burnout. Other work environment factors
      functioned as independent predictors of burnout.

PMID- 9621741
TI  - Objective analysis of text: II. Using an emotional compass to describe the
      emotional tone of situation comedies.
AB  - Transcripts for episodes from 9 situation comedies (roughly 27,000 words in
      total) were scored by the program TEXT.NLZ in terms of emotional tone. To promote
      ease of interpretation scores for the dimensions of pleasantness and activation
      were depicted as vectors in a normative emotional space. Both numerical and
      figural representations of the data indicated that the words used in situation
      comedies were pleasant and mildly active, with small differences occurring
      between comedies. The emotional characteristics of situation comedies stood out
      in comparison to those of several other texts depicted in the same emotional
      space.

PMID- 9621742
TI  - Positive and negative affect in the factor structure of the State-Trait Anxiety
      Inventory for Japanese workers.
AB  - The factor structure of Form Y of the State-Trait Anxiety Inventory (STAI-Y) was
      examined with 1,862 Japanese adult workers (1,509 men, 353 women). The initial
      principal component analysis extracted three factors based on the scree test. All
      20 state (S-Anxiety) and 20 trait (T-Anxiety) items had dominant salient loadings
      on the first factor, which reflected "over-all anxiety." The three factors
      identified by an oblique (promax) rotation were labeled "anxiety-absent," "state
      anxiety-present," and "trait anxiety-present." All 20 items with dominant salient
      loadings on the first oblique factor were clearly grouped on the basis of their
      content, indicating the absence of anxiety. The second and third oblique factors,
      defined almost entirely by the STAI-Y anxiety-present items, clearly reflected
      the state-trait distinction in this sample of Japanese workers.

PMID- 9621743
TI  - Stability of some hypothesized psychological determinants of fertility control.
AB  - Ratings of Self-Status International, a scale designed to measure behavioral and
      attitudinal correlates of fertility control, was administered to 95
      undergraduates on two occasions four weeks apart to estimate the stability of the
      12 measured factors. The test-retest correlation of scores from the two times was
      .58. Ten of the 12 factor scores had estimates of stability ranging between .48
      and .69, but two factors yielded coefficients of .23 (p < .05) and .32 (p < .01)
      only, indicating need for revision or reformulation.

PMID- 9621744
TI  - MMPI-A profiles of Hispanic adolescents.
AB  - A study was conducted to compare validity, clinical, content, and supplementary
      scale scores of Hispanic adolescents to normative data on the MMPI-A. Volunteers,
      30 boys, 17 girls, were Hispanic adolescents, aged 14 to 18 years from school and
      after-school settings. Analysis indicated elevated T score means on F1 (66), F2
      (68), F (68), L (61), Hs (61), D (63), Sc (62), A-hea (63), A-biz (63), A-lse
      (61), A-las (60), A-sch (61), and IMM (61) scales for boys. Scores for low
      aspirations, low self-esteem, immaturity, and school problems were all
      interrelated. For girls, scores on no scales were elevated, but on several scales
      mean T scores, Hs, Hy, Ma, Si, A-anx, A-obs, A-hea, A-ang, A-las, MAC-R, and ACK,
      were below average. This suggests the MMPI-A may underpathologize for girls.
      Consistent with previous findings, the boys scored higher on the Immaturity Scale
      than the girls. It was speculated that the boys' dislike for school and low
      aspirations were related to the lower education and employment of their fathers
      compared to those for the normative sample. The A-las, A-sch, and IMM scales may
      prove to be useful in identifying adolescent boys "at-risk" for dropping out of
      school, if replication with much larger samples confirms present findings.

PMID- 9621745
TI  - The legacy of Viktor Frankl: an appreciation upon his death.
AB  - Viktor Frankl's death in September of 1997 left a void in psychology and
      psychiatry. Frankl stressed that meaning and purpose are of paramount importance
      throughout people's lives. Frankl's own life was an example of his philosophy put
      into action.

PMID- 9621747
TI  - Validation of a self-report measure of somatic health.
AB  - The primary purpose was to assess the validity of a new self-report inventory of
      general somatic health status. In addition, we sought to examine the influence of
      social desirability and negative affectivity on health reports and to learn
      whether asking respondents to report concrete, memorable aspects of illness
      episodes such as seeing a doctor or staying home in bed for all or most of a day
      would enhance validity. The somatic component of the Cornell Medical Index was
      used as a criterion measure of health status because that Index has been shown to
      reflect medical records with great accuracy. Scores on the new health inventory
      correlated highly with the Cornell somatic scores, and this relationship was
      independent of negative affectivity and social desirability. The addition of the
      "concrete, memorable" aspects of illness accounted for no additional variance in
      the Cornell Index somatic scores beyond that accounted for by mere reporting of
      the presence of the symptom or illness. This study offers evidence supporting the
      validity of the Inventory of Health Status as a predictor of somatic health
      independent of social desirability and negative affectivity and also indicates
      that a simple indication of whether the patient had the symptoms is sufficient.

PMID- 9621746
TI  - Effects of risk factors on adolescents' resiliency and coping.
AB  - The relationships among five factors characterized as placing adolescents at risk
      for behavioral problems such as dropping out of school or drug and alcohol use,
      and resiliency and coping were evaluated for a sample of 392 students in Grades 7
      to 12. Students self-reported to be at-risk differed in scores on resiliency but
      not in coping from those with no self-reported risk factors.

PMID- 9621748
TI  - Associations of attributional dimensions with emotions in academic achievement.
AB  - To examine relationships between causal dimensions and affects in academic
      achievement, 87 college students were asked to complete a questionnaire, designed
      to assess their reactions to the outcome of a midterm examination. The
      questionnaire consisted of two kinds of measures, causal dimensions and affects.
      Multiple regression analysis showed the relations of attributional dimensions and
      the midterm examination outcome to the affective reactions; these results were
      discussed.

PMID- 9621749
TI  - Continuity of affiliative relationships among infants and juveniles in a free
      ranging group of Japanese monkeys (Macaca fuscata).
AB  - 5 infants were observed during the first 13 mo. after birth in a free-ranging
      group of Japanese monkeys (Macaca fuscata) to examine whether they maintained
      relatively frequent affiliative relationships with particular immature
      individuals. The number of immature affiliative partners rapidly increased from
      the first 3-mo. period after birth to the second 4-mo. period after birth, and
      the infants thereafter maintained affiliative relationships with particular
      individuals, mostly same-aged infants, at least in the second half of their first
      year. These findings show that infants were likely to interact with a larger
      number of different animals in the early stage of development, and thereafter
      selected particular individuals with whom they maintained affiliative
      relationships. The effects of sex on the selection of these long-term partners
      are also discussed.

PMID- 9621750
TI  - Narcissism, need for power, and social interest.
AB  - Significant positive correlations were separately observed for both 31 men and 38
      women college students between measures of narcissism and need for power. Neither
      the narcissism nor the need for power measure correlated significantly with
      social interest.

PMID- 9621751
TI  - [Molecular biology. Basis for increased understanding of diseases and improved
      diagnostics].

PMID- 9621752
TI  - [Is it possible to reduce sick leave by exercise?].

PMID- 9621753
TI  - [And she will give birth in pain].

PMID- 9621754
TI  - [Cyclooxygenase-1 and cyclooxygenase-2--important for the clinicians?].

PMID- 9621755
TI  - [Laparoscopic cholecystectomy].
AB  - The appropriateness of a laparoscopic approach to cholecystectomy in community
      hospital settings has been questioned. To address this issue a prospective study
      of outcomes of laparoscopic cholecystectomies performed during a three year
      period at Telemark Community Hospital was undertaken. There were 229 procedures
      performed by five surgeons. 24 (10.5%) of the attempted laparoscopic
      cholecystectomies were converted to open cholecystectomies. The average hospital
      stay after laparoscopic cholecystectomy was 3.0 days (SD = 2.6). Minor
      intraoperative complications (gall bladder perforation, gall bladder bed
      bleeding) occurred in 43% of the laparoscopic procedures. There were nine cases
      (4.4%) of major intraoperative complications which included laceration of the
      common bile duct (n = 4, one discovered during surgery), ileal perforation (n =
      1) and laceration of the liver (n = 4). The frequency of postoperative
      complications after laparoscopic cholecystectomy was 8.8%. Bile peritonitis was
      observed in three patients, of whom one died. There were no significant
      differences in intra- and postoperative complications between the surgeons
      performing the operations. The present results support the argument that
      laparoscopic cholecystectomies can be performed safely and effectively in
      community hospitals.

PMID- 9621756
TI  - [Peroral anticoagulant therapy--are the TT-values reliable?].
AB  - As part of the Norwegian Medical Association's quality assurance programme for
      the primary health care sector we have investigated the lasting quality of the
      specimens drawn for determination of Thrombotest. Blood drawn into siliconated
      glass tubes resulted in varying Thrombotest values, depending on the time of
      analysis after specimen collection. Reliable Thrombotest values are needed to be
      able to administer the correct dosage of warfarin. Thrombotest analysis should
      therefore be performed within two hours, or after 48 hours of specimen
      collection.

PMID- 9621757
TI  - [Obstetric analgesia in Norwegian hospitals].
AB  - We report the results of a questionnaire sent to anaesthetists and midwives on
      the use of obstetric analgesia and anaesthesia in Norwegian hospitals in 1996.
      95% of the 49 hospitals involved responded to the questionnaire, representing a
      total of 56,884 births. The use of epidural analgesia in labour varied from 0 to
      25% in the different hospitals with a mean value of 15%. Epidural analgesia was
      much more widely used in university and regional hospitals than in local
      hospitals (p < 0.001). Five of the local hospitals did not offer epidural
      analgesia during labour at all. The combination of low-dose local anaesthetic and
      an opioid (either sufentanil or fentanyl) had not been introduced in nine of the
      hospitals (20%). The optimal use of epidural analgesia to relieve labour pain was
      judged to be more frequent by the anaesthetists than by the midwives (19% versus
      11%, p < 0.01). In response to what factors limited the frequency of epidural
      analgesia, the anaesthetists specified factors related to the attitude of the
      midwife, and the midwives specified factors related to the anaesthetist. Only
      five of the hospitals provided written information on the various analgesic
      methods that could be employed during labour. The majority of midwives considered
      the analgesic methods employed on their maternity ward to be good or excellent.
      The frequency of Caesarean section was 12%; spinal anaesthesia was used in 55%,
      epidural anaesthesia in 17%, and general anaesthesia in 28% of the cases.

PMID- 9621758
TI  - [Mercury and dental amalgam fillings].
AB  - During 1993-95 a total of 169 patients (112 women, 57 men) with a wide range of
      complaints associated with earlier or present amalgam fillings were seen by the
      "Dental Biomaterials Adverse Reaction Unit" in Norway. Most patients had amalgam
      fillings; 19 had removed all amalgam, and 14 were in the process of replacing the
      amalgam fillings with other materials. Predominant symptoms were of a subjective
      and general nature (96% of the patients). Muscle and joint pain, headache,
      dizziness and feeling exhausted comprised the most common symptoms. Intra-oral
      pathology was observed in 48%. There was a correlation between the amount of
      amalgam ("amalgam score") and urinary mercury. Those without amalgam fillings and
      significantly lower values (median = 1.6 micrograms mercury/g creatinine) than
      those with amalgam fillings (medians: with amalgam = 3.5 micrograms/g; with
      partial removal of amalgam = 2.7 micrograms/g). Overall, in the present group of
      patients, no statistically significant correlation seemed to exist between the
      type and number of subjective symptoms or objective findings and the urinary
      mercury. This would indicate therefore that there is no straightforward
      association between urinary mercury and symptoms in the present group of
      patients.

PMID- 9621759
TI  - [Epidural obstetrical analgesia--a friend or an enemy?].
AB  - Epidural analgesia in labour using local anaesthetics is very efficient, but the
      technique has been associated with undesired motor block and an increased use of
      instrumental deliveries. A new epidural analgesia technique, using a combination
      of low-dose local anaesthetics and opioids (fentanyl and sufentanil), has
      recently come into practice. The new epidural technique provides excellent
      analgesia, minimises motor block, allows the mother to ambulate, and minimises
      the need for instrumental delivery. Furthermore, it constitutes a good
      alternative to parenteral pethidine. We are of the opinion that all pregnant
      women should be given detailed information about both the benefits and the
      possible side-effects of epidural analgesia in good time before they go into
      labour. This will allow them to participate more actively in deciding whether or
      not to use analgesia during labour. Optimal use of epidural analgesia not only
      depends on the availability of a 24-hour anaesthesia service, but also on
      adequate knowledge and the cooperation and enthusiasm of all those involved,
      namely midwives, obstetricians and anaesthesiologists.

PMID- 9621760
TI  - [Complications during and after surgery and childbirth where spinal or epidural
      analgesia is used. Guidelines for safe practice].
AB  - When complications and neurological sequelae occur during a spinal or epidural
      anaesthetic the causes are clearly related to the procedures in the following
      cases: severe haemodynamic or respiratory derangement, documented needle trauma
      of nerve fibres, intraspinal haematoma in anticoagulated or heparinized patients,
      and epidural infection where an infected epidural catheter entry site is
      documented. A number of well documented cases have been published in which
      surgery or patient-related pathology were primary causes of "typical" spinal or
      epidural neurological complications. These emphasize the importance of searching
      for other risk factors of neurological sequelae after surgery or child birth in
      cases where there is no obvious deviation from the normal epidural or spinal
      procedures. Increased focus on the infrequent, but serious complications of these
      essentially very safe techniques for surgical anaesthesia and pain relief should
      serve to increase our vigilance, but should not reduce the application of spinal
      and epidural analgesia. Guidelines are offered for the effective and safe
      practice of spinal and epidural anaesthesia and pain relief: adequate supervision
      of trainee anaesthetists, vigilant monitoring for early detection and handling of
      complications, and trained nurses on surgical wards to monitor and handle
      patients during epidural analgesia are important. Sufficient readiness for urgent
      handling of the very rare, but devastating complications of intraspinal bleeding
      or infection is an absolute necessity.

PMID- 9621762
TI  - [Prevention of suicide among young people--recent experiences from the armed
      forces].
AB  - Each year about 70% of all 19-year old males are enlisted to the Norwegian Armed
      Forces. The rapid rise in the number of suicides among young people will
      therefore inevitably be reflected among conscripts. Studies of epidemiology and
      risk factors have led to the development of a specific suicide prevention
      programme which includes educational, leadership and welfare elements, as well as
      efforts initiated through the military health care service. In addition, an
      emergency telephone service is available 24 hours a day. This suicide prevention
      programme, which has its origins in the military chain of command rather than the
      medical service, has so far been very well received and implemented throughout
      the Armed Forces.

PMID- 9621761
TI  - [Does physical exercise at the workplace have any effect on sick leave?].
AB  - The objective of the study was to ascertain whether physical activity at the
      workplace reduces the amount of sick leave. The databases Medline and Spri-line,
      reference lists, and professional expertise were consulted for information on the
      subject. We included random controlled trials, and controlled trials studying the
      effect on sick leave of physical activity at the worksite. Four trials were
      identified, including one carried out in Norway. The small number of trials
      limits the value of any conclusions and highlights the need for more research.
      The results of the four trials do not indicate that physical activity at the
      workplace reduces sick leave.

PMID- 9621763
TI  - [Molecular genetic diagnostics. Technology for detecting mutations in DNA].
AB  - Analyses of the genetic material in both inherited and acquired diseases such as
      cancer are already part of the repertoire of many laboratories. Over the last ten
      to fifteen years research has revealed a very complex human DNA, and shown that
      the molecular basis for disease is both intricate and variable. Methods for
      detecting the various categories of genetic changes are needed. These methods
      should be simple, quick and easy to perform, and cost-effective, and at the same
      time be both specific and sensitive. No single technology can fulfil all these
      criteria, and a variety of methods has therefore been introduced. In this
      overview we describe the different methods and their strengths and limitations.

PMID- 9621764
TI  - [Molecular biology diagnostics of hereditary metabolic diseases].
AB  - Metabolic diseases are often a result of monogenic inheritance and are suitable
      subjects for molecular diagnosis. Much progress has been made on research into
      this group of diseases, and further advances are expected after the completion of
      the Human Genome Project (HUGO) and as a consequence of improved molecular
      genetic methods. Although it is possible to diagnose many metabolic disorders by
      biochemical analyses of enzyme function, the underlying molecular genetic defects
      must be identified in order to be able to make accurate diagnoses of patients and
      their relatives. A molecular diagnosis is also a pre-condition for gene therapy.
      It is of paramount importance that more knowledge is gained of the correlation
      between genotype and phenotype for the genetic counselling of patients and their
      families. Important challenges at the present time are how to achieve a better
      understanding of the molecular and metabolic basis for the way in which diseases
      manifest themselves clinically and the factors which modify the phenotype.

PMID- 9621765
TI  - [The accreditation process at the Hormone Laboratory, Aker hospital].

PMID- 9621766
TI  - [Nervous system damage caused by solvents].

PMID- 9621767
TI  - [Clostridium difficile-associated diarrhea treated with homologous feces].

PMID- 9621768
TI  - [Heavy burden on the patient's back].

PMID- 9621769
TI  - [Social inequality and health--genetic causes?].

PMID- 9621770
TI  - [Estrogen substitution is better than alendronate (Fosamax)].

PMID- 9621771
TI  - [Antidepressive agents and physical therapy].

PMID- 9621772
TI  - [Exposure to mercury from dental amalgam].

PMID- 9621773
TI  - [A cohort of newborn infants, drugs and pregnancy].

PMID- 9621774
TI  - [Drugs and health--patients in focus?].

PMID- 9621775
TI  - [NSAID--non-steroidal anti-inflammatory agents. Their use and new perspective].

PMID- 9621776
TI  - [Atrial fibrillation and anticoagulant therapy].

PMID- 9621777
TI  - [Cancer registration in the Faeroe Islands].
AB  - The main purpose was to establish a cancer registry which could provide data for
      the treatment and control of cancer in the Faroe Islands. The registry should
      also be useful for epidemiological research in the future to pinpoint causes of
      cancer. The initiation of the registry is a result of a workgroup with members
      from the Faroes Hospital and Health System and from the Institute of Cancer
      Epidemiology at the Danish Cancer Society. The data items collected in the Faroes
      registry are identical with the data items in the Danish Cancer Registry. To
      provide a basis for the registry we have performed a retrospective data
      collection identifying all cancer cases in the Faroes for the 15 year period 1979
      1993. All hospital records and death certificates in the period were scrutinized.
      The official initiation of the Faroes cancer registry was on 1, January 1994.

PMID- 9621778
TI  - [Still disease in adults].
AB  - Adult onset Stills disease (ASD), an adult variant of systemic onset juvenile
      rheumatoid arthritis, is a rare disease entity. The diagnosis is solely a
      clinical one and often difficult. Clinical and laboratory features are not
      pathognomonic. The diagnosis of ASD has to be considered in patients with high
      spiking fever, transient rash, arthralgias, oligo- or polyarticular arthritis,
      leukocytosis, sore throat, lymphadenopathy and/or splenomegaly, liver dysfunction
      and high serum ferritin levels. We give a brief review of the clinical features,
      differential diagnosis, treatment and prognosis.

PMID- 9621779
TI  - [Multiresistant tuberculosis in Denmark 1993-1996].
AB  - Infections with multiresistant tubercle bacilli have also become a problem in the
      rich part of the world. The reasons are lack of compliance in patients with life
      style problems and ineffectiveness of the health system due to lack of fundings.
      During a four year period, 1993-1996 ten patients were seen in Denmark with
      tuberculosis due to multiresistant Mycobacterium tuberculosis. Nine were infected
      abroad, one developed MDR-TB during treatment in Denmark. It is possible to cure
      these patients, but it is expensive and takes a long time. In the future more
      cases created within Denmark are likely to be seen due to lack of funding for the
      tuberculosis programme and, depending on immigration, further cases created
      abroad are expected.

PMID- 9621781
TI  - [Nutritional status of Danish patients with rheumatoid arthritis and effects of a
      diet adjusted in energy intake, fish content and antioxidants].
AB  - This study deals with the nutritional status of Danish rheumatoid arthritis (RA)
      patients and addresses the question whether or not RA can be directly influenced
      by dietary manipulation. In a prospective, single-blinded study of six months'
      duration, 109 patients with active RA were randomly assigned to treatment with or
      without a specialized diet. The energy consumption was adjusted to normal
      standards for body-weight and the intake of fish and antioxidants was increased.
      A daily food diary was completed by the patients, and the total intake of 47
      different food-elements was calculated. Nutritional status together with disease
      activity parameters were recorded. At baseline, the Danish RA-patients had
      neglected food habits with a significant reduction in intake of total energy, of
      D-vitamin and of E-vitamin. A very low intake of n-3 fatty acids was also found.
      During the study, 28 of the 109 patients dropped out, introducing a confounding
      effect on the overall result. In the remaining 81, those following the diet
      demonstrated a significant improvement in the duration of morning stiffness, the
      number of swollen joints, the pain status and reduced the cost of medicine, while
      doctors' global assessment, laboratory data, X-ray and the daily activities were
      unaltered. In conclusion, dietary analysis and appropriate, corrective advice
      should be offered to Danish RA patients.

PMID- 9621780
TI  - [Rheumatoid arthritis and risk of cancer].
AB  - In the current study we linked data from the Danish Hospital Discharge Register
      and the Danish Cancer Registry to estimate cancer occurrence among more than
      20,000 patients hospitalized at least once with rheumatoid arthritis during 1977
      1987. During a follow-up interval of up to 15 years, we found increased risks of
      non-Hodgkin's lymphoma, Hodgkin's disease and lung cancer, while the risk of
      colorectal cancer was decreased. These findings were all in agreement with the
      results of previous studies from two other Nordic countries, which were based on
      a similar type of data. We also found an excess of non-melanoma skin cancer and a
      deficit of female breast cancer, of which only the breast cancer observation had
      been seen in an earlier study.

PMID- 9621782
TI  - [Bottle injuries in Denmark 1991-1995].
AB  - In the period from 1991-95, 1843 injuries caused by bottles were reported to the
      Danish EHLASS register, the latter representing 14.2% of the total number of
      patients seen in the Emergency Room in Denmark. The reports were classified as
      sharp or blunt injuries; age, sex, and body localisation were registered, and the
      injuries were grouped into eight body localisations. Hand injuries made up
      largest group (62%), and of these 92% were sharp injuries. The rest of the
      injuries (38%) were spread over the other zones, each representing 3-11%. Among
      the injuries there was a significant overrepresentation of males and young people
      between 10-24 years of age. Nearly 30% of the injuries were associated with a
      fall. We estimate that the total number of injuries caused by bottles was
      2596/year, and that the incidence rate was 4.98/10,000 person years.

PMID- 9621783
TI  - [Two cases of Still disease in adults].
AB  - We describe two cases of adult onset Stills disease. Both patients presented with
      typical features of adult Stills disease: high spiking fever, arthralgia, oligo-
      and polyarticular arthritis, transient rash, sore throat, lymphadenopathy and
      leukocytosis. Both patients failed to improve when treated with nonsteroidal
      antiinflammatory drugs (NSAIDs) and azathioprine, but responded adequately when
      sulfasalazine was added to the medication. It is suggested that sulfasalazine is
      a useful adjunct if the clinical response to NSAIDs is not sufficient.

PMID- 9621784
TI  - [Brown syndrome in an adult patient with morbus Still].
AB  - A 25 year-old woman, known to be suffering from destructive rheumatoid arthritis,
      was admitted to the hospital due to influenza-like symptoms lasting three weeks.
      Adult Still's disease was diagnosed. During her disease she developed painful
      ophthalmoplegia due to tenosynovitis of the superior oblique muscle and tendon
      sheath (Brown's syndrome). Total resolution was obtained within three weeks of
      corticosteroid therapy.

PMID- 9621785
TI  - [Cirrhotic cardiomyopathy--true or false?].

PMID- 9621786
TI  - [About olive oil].

PMID- 9621787
TI  - [Destruction of cartilages caused by NSAID preparations?].

PMID- 9621788
TI  - [Amino acids and nomenclature--again].

PMID- 9621789
TI  - [Science or politics?].

PMID- 9621791
TI  - [Screening for cervix cancer].

PMID- 9621790
TI  - [Every generation has to learn everything from start].

PMID- 9621792
TI  - [NSAID--non-steroidal anti-inflammatory agents. Used too much? Which preparations
      should we choose? Damage of the cartilage?].

PMID- 9621793
TI  - [Treatment of rectal cancer--centralization is necessary].

PMID- 9621794
TI  - [Prevention and treatment of osteoporosis].

PMID- 9621795
TI  - [Alzheimer's diseases--etiology and pathogenesis].

PMID- 9621796
TI  - [Does colonic J-pouch after low anterior resection of rectal cancer give a better
      functional result?].
AB  - Low anterior resection (LAR) with mesorectal excision for adenocarcinoma of the
      rectum leads to low colorectal or coloanal anastomosis, and often poor functional
      results. Increased stool frequency and urge are common after the operation, and
      some have anal incontinence. Construction of a neo-rectum, in the form of a
      colonic J-pouch improves the functional results to some extent. Patients with a
      colonic J-pouch have significantly lower stool frequency and perhaps also fewer
      symptoms of urge and incontinence than patients with a straight coloanal
      anastomosis. If part of the rectum is preserved, the benefit of a pouch is
      doubtful. The overall quality of life after the operation in patients with a J
      pouch is not different from quality of life in patients with a straight coloanal
      anastomosis. Patients with a pouch may have trouble emptying the reservoir, this
      is less pronounced if the pouch is shortened to 5 cm. It is not proved with
      certainty that patients with a colonic J-pouch have fewer anastomotic leakages
      than patients with a straight coloanal anastomosis. It is concluded that with an
      anastomotic height below 5 cm a pouch apparently improves the functional results
      after LAR for adenocarcinoma of the rectum, while the benefit of a pouch above
      this anastomotic height is doubtful.

PMID- 9621797
TI  - [Severe infections after epidural catheterization].
AB  - The paper reviews the literature relevant to the formation of spinal epidural
      abscess with or without concurrent meningeal infection following epidural
      catheterisation. The incidence of spinal epidural abscess lies probably in the
      area of 1:5000 catheterisations. Immunocompromised patients and patients with
      catheters in situ for more than 48 hrs. are particularly prone to develop
      epidural abscesses. S. aureus is isolated in 35-82% of the cases. The diagnosis
      based upon clinical findings, laboratory studies and MRI or CT plus myelography.
      The mortality is 5-10%. The treatment consists of removal of the catheter,
      microbiological studies, surgical decompression of the spinal cord, and prolonged
      antibiotic treatment. It is suggested that insertion of epidural catheters is
      performed under strict sterility, and that disposable syringes and unbroken vials
      are used for each injection, which should be administered through an epidural
      filter. The dressing should be changed daily simultaneously with review of the
      patient and the insertion site.

PMID- 9621798
TI  - [Utilization of calcium, vitamin D and diphosphonates used in the treatment of
      osteoporosis in Denmark 1994-1996. An epidemiological analysis of nationwide
      prescription data].
AB  - The aim of this study was to explore the utilization of calcium, vitamin D and
      bishosphonates used in treatment of osteoporosis. The data derive from the
      Register of Drug Statistics at the Danish Medicines Agency. The analysis
      encompassed 112,300 prescriptions presented by 25,692 patients during a period
      from 1 January 1994 to 30 June 1996. The consumption of calcium decreased, while
      the consumption of bisphosphonates increased 971% during the period. The one-year
      prevalence of use of calcium, vitamin D and bishosphonates was 3.5 per 1000 in
      1995 with a female to male ratio of 6.8:1. Use was most common in the age group
      75-79 years. Twenty-seven percent of the patients had used corticosteroids
      previously to being treated for osteoporosis; 1.4% of the patients had used
      cumulative corticosteroid doses greater than 10 g. These heavy users were treated
      with five times larger doses against osteoporosis than patients not treated with
      corticosteroids.

PMID- 9621799
TI  - [Circumcision by the method of Lucas].
AB  - Circumcision a.m. Lucas is described and the results are given in 85 boys with a
      median age of four years (range, 2-14 years). The postoperative period was
      uncomplicated in 79% of the cases. The most frequent complication was bleeding
      (8%), but reoperation was only needed in one case. Haematomas were registered in
      4% of the boys. Glans was free or nearly free in 89% of the cases. Only 12% of
      the families were dissatisfied with the length of the remaining prepuce: the
      Muslim parents found the prepuce too long (8%), the Danish parents found that too
      much of the prepuce had been removed (4%). Circumcision a.m. Lucas gives uniform
      results, is without major complications, and can be performed on medical as well
      as ritual indications.

PMID- 9621800
TI  - [Interobserver variation in wound assessments].
AB  - Agreement in describing a chronic leg ulcer is pivotal in identifying and
      treating impediments to the healing process. Six nurses and one doctor without
      special experience with wound healing registered wound related diagnoses for a
      five month period. On average each patient was seen by three observers yielding
      270 registrations. Agreement beyond chance (global kappa) showed poor to moderate
      agreement. Agreement was best for the yellow or malodorous wound and lowest for
      cellulitis, hypergranulation and peripheral pulses. This emphasizes the
      importance of allocating wound treatment to specialist departments with access to
      paraclinical investigations.

PMID- 9621801
TI  - [Anal and urinary incontinence after obstetric anal sphincter rupture].
AB  - The aim of the study was to assess the long term impact of obstetric anal
      sphincter rupture on the frequency of anal and urinary incontinence, and identify
      factors to predict patients at risk. In 94 consecutive women who had sustained an
      obstetric anal sphincter rupture, anal manometry, anal sphincter electromyography
      and pudendal nerve terminal motor latency at three months post partum was
      performed. A questionnaire regarding incontinence was sent between two to four
      years post partum. Forty-two percent of responders had anal incontinence, 32% had
      urinary and anal incontinence. Overall, 56% of the women had incontinence
      symptoms. The occurrence of anal incontinence was associated with pudendal nerve
      terminal motor latencies > 2.0 milliseconds and the occurrence of urinary
      incontinence was associated with the degree of rupture, the use of vacuum
      extraction and previous presence of urinary incontinence. Thirty-eight percent of
      the women with incontinence wanted treatment, but only a few had sought medical
      advice.

PMID- 9621802
TI  - [Effect of early postoperative enteral nutrition on postoperative infections].
AB  - We undertook this study to test the hypothesis that early enteral nutrition might
      reduce the incidence of serious complications after major abdominal surgery. In a
      randomized double blind prospective trial 30 patients received Nutridrink and 30
      patients received placebo through a nasoduodenal feeding tube. On the day of
      operation the patients were given median 600 ml nutrition/placebo, 60 ml/h. On
      the first postoperative day the patients received median 1000 ml
      nutrition/placebo, second day median 1200 ml nutrition, 1400 ml placebo, third
      postoperative day median 1000 ml nutrition, 1150 ml placebo and 4th postoperative
      day median 1000 ml nutrition, 800 ml placebo. All patients were followed for 30
      days by the same investigator. The two groups were not different with regard to
      nutritional status and type of operation. The rate of postoperative infectious
      complications was significantly lower in the nutrition group, 2/30 compared to
      14/30 in the placebo group (p = 0.0009). We conclude that early enteral nutrition
      given to patients after major abdominal surgery is followed by a major reduction
      in infectious complications.

PMID- 9621803
TI  - [Interaction between warfarin and coenzyme Q10].
AB  - Coenzyme Q10 (Ubidecarenone) is marketed as a dietary supplement. Drug
      interaction between coenzyme Q10 and warfarin has previously been reported. In
      the present case, a 72-year-old female treated with warfarin showed less
      responsiveness to warfarin than previously. It appeared she had taken coenzyme
      Q10, and when this was stopped, her responsiveness to warfarin was the same as
      before. Coenzyme Q10 is chemically similar to K-vitamins, which may explain the
      interaction with warfarin. Patients in treatment with warfarin should be aware of
      the possible risk of treatment failure when taking coenzyme Q10. The need for
      questioning patients concerning not only medications but also use of dietary
      supplements and alternative medications is emphasised.

PMID- 9621804
TI  - [Castleman's disease--difficult diagnosis].
AB  - A case of Mb. Castleman of the localized plasma cell type is reported. This
      disease expresses several symptoms from different organ systems and therefore an
      extensive investigation program is often performed. Diagnosis is possible through
      consideration of all clinical components at the same time: Refractory anaemia,
      high and refractory SR, weight loss, B-symptoms, but at the same time a
      relatively good health. CT-scan-demonstration of a localized tumour is an
      important clue. Histopathologically, the tumour shows vascular hyperproliferation
      and plasmacytosis of varying maturation. Immunophenotyping of the plasma cells
      and immunoblasts usually reveals a polyclonal population. Needle biopsies from
      several regions may be necessary to detect the polyclonality, because
      monoclonality is often widespread locally in the tumour. HHV8 is correlated to
      the multicentric PC-type of Mb. Castleman. However, no HHV8 was found in this
      case.

PMID- 9621805
TI  - [Prevention of hip fractures].

PMID- 9621806
TI  - [Drug information center at the Center for Clinical Pharmacology in Odense].

PMID- 9621807
TI  - [CA 125 in epithelial ovarian cancer].

PMID- 9621808
TI  - [Bipariental failure in Alzheimer's disease].

PMID- 9621809
TI  - [Alendronate].

PMID- 9621810
TI  - [Main principles of diagnosis of primary open-angle glaucoma].
AB  - Symptoms of primary open-angle glaucoma can be divided into main and accessory
      and risk factors. The main symptoms are increased intraocular pressure and
      changes in the visual field and optic disk characteristic of glaucoma. The
      accessory symptoms and risk factors are a family history of glaucoma, diabetes
      mellitus, myopia, poor discharge of aqueous humor, pseudoexfoliative syndrome,
      elements of goniodysgenesis and depositions of pigmented granules in the anterior
      chamber corner, and asymmetric intraocular pressure, humor discharge, and extent
      of optic disk excavation. Causes and diagnosis of nonglaucomatous hypertension
      and normal-pressure glaucoma are discussed.

PMID- 9621811
TI  - [Comparative study of antiradical effects of several antiglaucoma drugs].
AB  - Studies of the in vitro inhibitory effects of drugs most often used in the
      treatment of primary glaucoma on the generation of the main active oxygen forms
      (hydroxyl radical, superoxide anion radical, singlet oxygen and radical products
      of hydrogen peroxide and peroxidase reaction) showed that antiradical activity is
      more intrinsic for thimolol and decreases in the following series: betoptic
      pilocarpinclofelin. This once more validates the efficacy of beta-blockers in the
      treatment of glaucoma and prevention of cataract associated with it.

PMID- 9621812
TI  - [Changes in regional hemodynamics indices in patients with open-angle glaucoma].
AB  - Changes in the hemodynamic parameters of the eye were examined in patients with
      primary open-angle glaucoma (OAG) in the well developed and far advanced stages
      with moderately increased (up to 32 mm Hg) and high (33 mm Hg and higher)
      pressure before and after surgery. Computer-aided vacuum ophthalmodynamometer was
      used with a sucking cup calibrated for two levels of ophthalmic tone, whose
      external diameter was 13 mm and funnel angle 60 degrees. A total of 59 patients
      (82 eyes) aged 50 to 84 years were examined, control group consisted of 18
      patients (36 eyes). Mean dynamic pressure in the orbital artery and perfusion
      pressure were measured, and the orbital-brachial coefficient estimated.
      Progressive decrease of perfusion pressure was paralleled by increase of the mean
      dynamic pressure in the orbital artery in patients with stages Iic and IIIb OAG
      and by its decrease in those with stage IIIc OAG. Such changes of the
      hemodynamics are explained by the compensatory work of the ocular bloodflow
      autoregulation mechanism in the first case and its failure in the second. After
      regression analysis, linear equations of the relationship between changes in the
      mean dynamic pressure and intraocular pressure were calculated. After surgery,
      changes in the hemodynamic parameters were followed up for 12 months in 27 eyes
      with well-developed condition and for 6 months in 13 eyes with far advanced
      condition.

PMID- 9621813
TI  - [Emergency penetrating keratoplasty in infective lesions of the cornea at the
      site of sutures].
AB  - Urgent perforating keratoplasty was carried out in 52 patients with infective
      involvement of the cornea at the site of sutures after cataract extraction,
      perforating keratoplasty, and treatment of penetrating wounds of the cornea. The
      inflammation was most often caused by Pseudomonas aeruginosa (32%), cocci
      (33.6%), and fungi (14.1%). The technique of perforating keratoplasty for cases
      with different localization and extent of purulent infiltration is described and
      results of pathohistological examination of removed disks presented. The authors
      emphasize the importance of timely removal of monofilament sutures and thorough
      care of sutured sites. Urgent perforating keratoplasty arrested acute
      inflammations in 90% of cases and preserved or improved visual acuity in 70% of
      cases.

PMID- 9621814
TI  - [Contusion ruptures of the ocular capsule along postoperative corneo-limbic
      scars].
AB  - Clinical picture, variants of surgical treatment, and anatomic and functional
      outcomes of contusion ruptures of the eyeball at the site of postoperative
      corneolimbic cicatrices are described. Such traumas can occur even 9-10 years
      after keratotomy. The majority of unfavorable outcomes in such patients are due
      to retinal and vitreous abnormalities, such as hemophthalmia or detachment of the
      retina. Ruptures of corneolimbic cicatrices in patients after cataract extraction
      with or without implantation of intraocular lenses are more frequent during the
      first months after surgery; an indirect contusion is sufficient to cause them.
      The incidence of fibrous capsule ruptures does not depend on the localization of
      the cicatrice and type of suture. Ruptures of cicatrices on artiphakic eyes
      almost always involve falling of intraocular lenses into the wound. An intact
      diaphragmatic function of the iris and transparent optic media are prognostically
      favorable factors in such patients.

PMID- 9621815
TI  - [Treatment of solitary subconjunctival cysts of filtration pad after fistulizing
      surgery of glaucoma].
AB  - The clinical picture and cytostatic treatment of solitary subconjunctival cysts
      of filtration pad after fistula-forming antiglaucoma surgery are described.
      Twenty-seven eyes with hypertension which developed as a result of
      subconjunctival cysts formed in the early postoperative period in 7% of patients
      operated on for open-angle glaucoma. Probable mechanisms of the pathogenesis of
      the formation of solitary cysts are discussed and 3-staged therapy proposed,
      including beta-blockers, perforation of the cyst wall by YAG laser, and, in 10%
      of cases with rigid cysts, microsurgical revision of filtration pad.

PMID- 9621816
TI  - [A new transplant for iridoplasty].
AB  - A new transplant is proposed for replacing extensive defects of the iris:
      cadaveric aortic wall. Experiments demonstrated that taking in of this graft
      courses as incomplete regeneration with partial taking in and replacement of the
      graft by cell elements of the iris with the formation of a cicatrice. Aortic wall
      transplant was used in the treatment of 4 patients.

PMID- 9621817
TI  - [Differentiation of corneal tissues (role of the nerve factor)].
AB  - The results of various experimental exposures of corneal tissue are presented.
      Morphological studies demonstrate a decrease of tissue differentiation and its
      accelerated growth and impairment of tissue relationships depending on injury to
      its nervous system. The author considers that the degree of tissue
      differentiation, tissue correlations, and functional intactness of tissue depend
      on the status of the nervous system.

PMID- 9621818
TI  - [Eye ointments eubetal and colbiocin in the treatment of chlamydial
      conjunctivitis].
AB  - The above ointments were used for local treatment of chlamydial conjunctivitis in
      325 patients. The results demonstrated their high efficacy, good tolerance,
      advantages over tetracycline ointment, and absence to toxic allergic reactions.

PMID- 9621819
TI  - [Prevention of visual fatigue in computer users by eyeglasses with spectral
      filters].
AB  - Color-contrast optic filters are developed for improving the color discriminating
      capacity of eyes exposed to video display terminals. These filters are applied as
      a coating on correcting or common glasses. Effects of such eyeglasses on visual
      functions accommodation, frequency-contrast sensitivity, and critical frequency
      of flashes fusion (CFFF) were studied in 23 PC users with visual acuity of 1.0
      with correction. Wearing of eyeglasses with filters promoted shifting of the most
      distant point of clear vision further and increased the accommodation volume,
      contrast sensitivity at the low and decreased it at the medium and high
      frequencies. CFFF was not changed. Wearing of eyeglasses with filters for 4 h of
      working at a display caused shifting of the nearest and most distant points of
      clear vision in comparison with the control group with the accommodation volume
      unchanged and preserved the high contrast sensitivity at the mean and low
      frequencies during the entire period of work. No changes in CFFF were noted.
      After 4 weeks of using eyeglasses with spectral filters, 86.9% of volunteers
      noted an improvement of visual working capacity and 13.1% considered there was no
      difference. Hence, eyeglasses with spectral filters are recommended as an
      ophthalmological measure preventing visual fatigue during long work with video
      displays.

PMID- 9621820
TI  - [Contrast sensitivity in amblyopia, abiotrophy and optic nerve atrophy in
      children].
AB  - The threshold spatial contrast sensitivity was assessed in children with
      amblyopia, tapetoretinal abiotrophy, and partial atrophy of the optic nerve of
      different origin. The measurements were carried out at spatial frequencies of 0.5
      22 cycle/grad. Tests with white, red, green, and blue arrays against a black
      background realized in the Zebra software for IBM computers with VGA or SVGA
      displays were carried out. Classification of curves representing the contrast
      sensitivity for the above conditions is proposed. Characteristics of the groups
      with the above diseases are described, based on the height, shape, and mutual
      position of the curves.

PMID- 9621822
TI  - [Local mechanisms of relationship between colloid-osmotic pressure and ophthalmic
      tone in patients with diabetes mellitus].
AB  - Forty-two patients (84 eyes) aged 35-73 were examined, 11 of these with type I
      diabetes mellitus and 31 with type II diabetes. All examinees were in the sub-
      and decompensation phase. Time course of glycemia and intraocular pressure was
      followed up (check-ups on an empty stomach and 1 h after eating). An increase of
      blood sugar level 1 h after eating is paralleled by a decrease of intraocular
      pressure. The main mechanism of inverse changes of ophthalmic tone under
      conditions of hyperglycemia is dehydration of ocular tissues.

PMID- 9621821
TI  - [Keratoconjunctivitis sicca in Sjogren's syndrome: diagnostic significance of
      relative protein composition of tears].
AB  - Six protein components were detected in the tears by exclusive high-pressure
      liquid chromatography. By their molecular weight, these components were
      identified as lacrimal prealbumin, human serum albumin, lactoferin, IgG, and IgA.
      The relative content of these proteins in tears correlates with the clinical
      picture of kerato-conjunctivitis sicca. Correlation coefficients (ci) were -0.66
      for lysozyme, -0.58 for prealbumin, 0.70 for serum albumin, -0.63 for
      lactoferrin, and 0.65 for IgA. Linear regression analysis showed that the
      relative content of IgA and serum albumin rapidly increased in the course of
      disease. The relative content of lysozyme, lactoferrin, and prealbumin dropped,
      but two times slower. The authors propose assessing the quantitative changes in
      the lacrimal protein composition by a special diagnostic parameter: P = sigma(dni
      di)ci/C, where dni and di are the mean relative levels of the protein component
      in health and disease, C the sum of absolute values of correlation coefficients
      for all components (C = sigma[ci]). The (dni-di) value reflects the effect of
      disease on changes in the relative content of each protein component and the ci/C
      value the intensity of this effect. This parameter can be used for assessing the
      involvement of the eyes in Sjogren's syndrome and monitoring the efficacy of
      treatment.

PMID- 9621824
TI  - [Use of monoclonal antibodies in the diagnosis of ophthalmic chlamydiosis].
AB  - A total of 168 patients with various ocular diseases were tested for Chlamydia.
      Scrapings off the conjunctiva were examined by the fluorescent antibody technique
      with monoclonal antibodies. A high diagnostic efficacy of the method in patients
      with acute and, which is even more important, with the subacute form of
      ophthalmic chlamydiasis was demonstrated. Moreover, the method effectively
      diagnosed ophthalmic chlamydiasis in patients with inflammations of the anterior
      and median segments of the eye of obscure etiology.

PMID- 9621823
TI  - [Morphogenesis of corneal epithelial-endothelial dystrophy (a comparative
      morphological analysis of corneal disks and biopsy specimens of the
      conjunctiva)].
AB  - The aim of this study was morphological analysis of corneal disks and
      conjunctival biopsy specimens in order to disclose the mechanisms of development
      of epithelial-endothelial dystrophy (EED) and validating pathogenetically-based
      therapy. Twenty-five patients were observed, 11 of these with implanted
      intraocular lenses of different localization. EED developed for 1 to 5 years.
      Sixteen biopsy specimens of the conjunctiva and 21 corneal disks were examined.
      The composition and index of inflammatory infiltrate, status and compactness of
      conjunctival vessels, severity of fibrosis, and mast cell degranulation were
      assessed. Mast cells play a positive role at the initial stages of tissue and
      cellular response to injury by regulating the formation of extracellular matrix
      and fibroblast proliferation. At the reparative stages of immune inflammation of
      the conjunctiva, mast cells are virtually the only cell population; fibrosis and
      sclerosis develop when the capillary bed is reduced, causing ischemic involvement
      of the anterior segment of the eye and dystrophic processes in the cornea. A
      differentiated approach to treatment of EED at the stages of immune inflammation
      and fibrosis is emphasized.

PMID- 9621825
TI  - [Results of immunogenetic typing of lymphocytes of patients with keratoconus].
AB  - Histotyping of HLA I antigens in 100 patients with keratoconus. Europeoids of the
      Chelyabinsk district, and of 701 controls (donors listed in the regional
      register) showed an increased incidence of HLA A28, B12, and B15, a decreased
      incidence of HLA B8, B13, and complete absence of HLA A11. Estimation of HLA
      haplotypes in keratoconus showed an increased incidence of haplotypes A1-B5
      (relative risk RR = 5.9), A2-B15 (RR = 3.34), A2-B27 (RR = 2.12), and A9-B21 (RR
      = 4.13) and decreased incidence of A1-B8 (RR = 0.31). The incidence of incomplete
      phenotypes was 27%. The most incident of incomplete phenotypes was A3-B35.
      Reliably linked HLA haplotypes A3-B7, A2-B27, A9-B21, and A9-B35 were typical of
      men with keratoconus, whereas A2-B21 haplotype was characteristic of the female
      patients.

PMID- 9621826
TI  - [A case of syphilitic uveitis].
AB  - A 43-year-old woman with alcoholism developed hearing loss, dizziness, unsteady
      walking, frequent urination, memory disorders, and later a manifest drop of
      bilateral vision. The patient denied syphilis. Examinations revealed bilateral
      panuveitis, bilateral neurosensory amblyacusia, vestibulopathy, and imperative
      urges to urination. Serological tests were positive with both Treponema and other
      than Treponema antigens. The cerebrospinal fluid was normal. Ampicillin therapy
      was ineffective. The clinical picture, diagnosis, and treatment of syphilitic
      uveitis are discussed; the authors point out that it is often associated with
      neurosyphilis. The condition is extremely rare nowadays.

PMID- 9621827
TI  - [Traumatic uveitis: the problem of pathogenetic therapy].

PMID- 9621828
TI  - Why do strangers feel familiar, but friends don't? A discrepancy-attribution
      account of feelings of familiarity.
AB  - Recent articles on familiarity (e.g. Whittlesea, B.W.A, 1993. Journal of
      Experimental Psychology 19, 1235) have argued that the feeling of familiarity is
      produced by unconscious attribution of fluent processing to a source in the past.
      In this article, we refine that notion: We argue that is not fluency per se, but
      rather fluent processing occurring under unexpected circumstances that produces
      the feeling. We demonstrate cases in which moderately fluent processing produces
      more familiarity than does highly fluent processing, at least when the former is
      surprising.

PMID- 9621829
TI  - What is the mechanism for fluency in successive recognition?
AB  - There are a number of reasons to believe that processing fluency may affect
      successive recognition judgements, but evidence about the mechanism for these
      effects is currently lacking. This study used a successive task design to examine
      whether subjective ease might underlie effects of fluency on recognition. At
      study subjects performed lexical decisions; in a subsequent test with studied and
      new items, subjects performed lexical decisions followed immediately by
      recognition or ease judgments. In a previous study we used that process
      dissociation procedure to show that recognition in a similar task was largely
      based upon fluency. In the present study, successive recognition judgments
      interfered with lexical decision performance to a greater degree than did ease
      judgments, suggesting that the recognition judgment was not automatic and
      involved processes additional to the judgment of ease. The data suggest that the
      fluency involved in successive recognition is more complex than a subjective
      judgment of ease of processing. One possible mechanism for fluency in recognition
      may be based upon reductions in the orientation of attention that accompany item
      repetition.

PMID- 9621830
TI  - Conceptually driven encoding episodes create perceptual misattributions.
AB  - Processing fluency caused by prior encoding of a word is shown to increased
      duration judgments about that word and to decrease brightness contrast judgments
      about its mask when the word is presented in a masked word identification task.
      These effects occurred following an encoding task that involved visual perception
      of the words (reading aloud) and a task that provided no direct visual experience
      (generation from a semantic cue). Analysis of judgments conditionalized on
      correct or failed identification of target words indicated that judgments were
      powerfully affected by successful identification. Subjective estimates of the
      proportion of targets that were previously studied suggested that awareness of
      prior occurrence followed as an attribution based on fluent word identification,
      rather than acting as a causal agent for identification or altered perceptual
      judgments. We conclude that prior perceptual and conceptual encoding episodes can
      contribute to fluent processing of target words on a subsequent masked word
      identification task and that, regardless of its source, this fluency is
      experienced in a generic form that is susceptible to attribution to various
      causes, including prior experience (creating a sense of recollection) and current
      stimulus conditions.

PMID- 9621831
TI  - On the relationship between recognition familiarity and perceptual fluency:
      evidence for distinct mnemonic processes.
AB  - Fluent reprocessing of perceptual aspects of recently experienced stimuli is
      thought to support repetition priming effects on implicit perceptual memory
      tests. Although behavioral and neuropsychological dissociations demonstrate that
      separable mnemonic processes and neural substrates mediate implicit and explicit
      test performance, dual-process theories of memory posit that explicit recognition
      memory judgments may be based on familiarity derived from the same perceptual
      fluency that yields perceptual priming. Here we consider the relationship between
      familiarity-based recognition memory and implicit perceptual memory. A select
      review of the literature demonstrates that the fluency supporting implicit
      perceptual memory is functionally and anatomically distinct from that supporting
      recognition memory. In contrast to perceptual fluency, recognition familiarity is
      more sensitive to conceptual than to perceptual processing, and does not depend
      on modality-specific sensory cortices. Alternative possible relationships between
      familiarity in explicit memory and fluency in implicit memory are discussed.

PMID- 9621832
TI  - Electrophysiological evidence for dissociable processes contributing to
      recollection.
AB  - This paper reviews a number of studies in which we have employed event-related
      potentials (ERPs) to investigate the cognitive processes which contribute to
      conscious recollection. Across a range of tasks (including recognition memory,
      source memory, associative recall and word-stem cued recall) there is evidence
      for the proposal that recollection involves processes which are both functionally
      and neurologically dissociable. This evidence takes the form of temporally and
      topographically dissociable ERP effects, which attain their maximum amplitude
      when elicited by items that satisfy operational definitions for having been
      recollected. The ERP effects are interpreted as reflecting retrieval and post
      retrieval processes which, we argue, constitute two separate components of
      recollection as defined within the process dissociation framework of Jacoby and
      colleagues. The ERP findings suggest that post-retrieval processing is
      particularly sensitive to task variables, implying that recollection may be
      neither functionally nor neurologically homogeneous.

PMID- 9621833
TI  - The relationship between remembering and knowing: a cognitive neuroscience
      perspective.
AB  - Cognitive neuroscience has provided strong support for the idea that there are
      multiple memory systems. Recent evidence suggests that remembering and knowing
      may be two types of recognition with different neural substrates. The
      remember/know distinction is not equivalent to the explicit/implicit distinction
      because both remembering and knowing are impaired after damage to medial temporal
      lobe structures. A number of converging lines of evidence suggest that the
      relationship between remembering and knowing is one redundancy, with "knowing"
      processes also active during remembering. Remembering appears to depend
      additionally on frontal lobe functioning.

PMID- 9621834
TI  - Predicting the future and reconstructing the past: a Bayesian characterization of
      the utility of subjective fluency.
AB  - The subjective sense of fluency with which an item can be perceived or remembered
      is proposed to be a vital cue in making decisions about the future memorability
      and the nature of our past experience with that stimulus. We first outline a
      number of cases in which such perceptual or retrieval fluency influences
      judgments both about our own future performance and our likely past experience,
      and then present a Bayesian analysis of how judgments of recognition--deciding
      whether or not a currently viewed item was studied at a particular point in the
      past--may incorporate information about the perceptual fluency of that item.
      Using a simple mathematical model, we then provide an interpretation of certain
      enigmatic phenomena in recognition memory.

PMID- 9621835
TI  - The influence of attention at encoding on direct and indirect remembering.
AB  - The relation between attention at encoding and direct (i.e., recognition) versus
      indirect (i.e., rapid reading) remembering was investigated. In Experiments 1 and
      2, color of print indicated whether to read an individual word aloud or to ignore
      it. This attentional manipulation reduced direct but not indirect remembering for
      the ignored words relative to the attended words. Apparently direct remembering
      is extremely dependent on attention at encoding. In Experiment 3, however,
      presenting two words simultaneously at study, with color now signifying which
      word to read and which to ignore, eliminated this dissociative effect of
      attention. Ignored words were not remembered on either test, although attended
      words were remembered well on both. Mere exposure is not sufficient to produce
      indirect remembering: Stimuli must be attended. Ignoring one stimulus in favor of
      processing another stimulus that is simultaneously presented and equally salient
      may prevent even the minimal attentional requirements of indirect remembering
      from being met, let alone the more stringent requirements of direct remembering.

PMID- 9621836
TI  - Levels of processing and selective attention effects on encoding in memory.
AB  - The purpose of the present study was to investigate the effects of selective
      attention and levels of processing (LOPs) at study on long-term repetition
      priming vis-a-vis their effects on explicit recognition. In a series of three
      experiments we found parallel effects of LOP and attention on long-term
      repetition priming and recognition performance when the manipulation of these
      factors at encoding was blocked. When a mixed study condition was used, both
      factors affected explicit recognition, while their effect on repetition priming
      was determined by the nature of the test. Shallow processing at test did not
      benefit from long-term repetition, regardless of whether the words had been
      studied deeply or shallowly. Selective attention affected long-term repetition
      priming in a semantic, but not in a lexical decision (LD), test. Regardless of
      study condition, retention lag affected long-term repetition priming only in the
      semantic test. These results suggest that if the experimental conditions allow
      scrupulous selection of attended and unattended information or narrow tuning to a
      shallow, pre-lexical LOP, implicit access to unattended or shallowly studied
      items is significantly reduced, as is explicit recognition. We suggest a
      conceptual framework for understanding the effects of LOP, attention, and
      retention interval on performance of explicit and implicit tests of memory.

PMID- 9621837
TI  - Why "sounds are judged longer than lights": application of a model of the
      internal clock in humans.
AB  - Three experiments, using temporal generalization and verbal estimation methods,
      studied judgements of durations of auditory (500-Hz tone) and visual (14-cm blue
      square) stimuli. With both methods, auditory stimuli were judged longer, and less
      variable, than visual ones. The verbal estimation experiments used stimuli from
      77 to 1183 msec in length, and the slope of the function relating mean estimate
      to real length differed between modalities (but the intercept did not),
      consistent with the idea that a pacemaker generating duration representations ran
      faster for auditory than for visual stimuli. The different variability of
      auditory and visual stimuli was attributed to differential variability in the
      operation of a switch of a pacemaker-accumulator clock, and experimental data
      suggested that such switch effects were separable from changes in pacemaker
      speed. Overall, the work showed how a clock model consistent with scalar timing
      theory, the leading account of animal timing, can address an issue derived from
      the classical literature on human time perception.

PMID- 9621838
TI  - Backward blocking and recovery from overshadowing in human causal judgement: the
      role of within-compound associations.
AB  - We replicated and extended a project by Dickinson and Burke (1996) that concerned
      human causal judgement. In a medical diagnostic setting, college students'
      ratings of the causal efficacy of target cues showed retrospective revaluation:
      relative to a proper control condition, ratings of target cues both increased
      ("recovery from overshadowing") and decreased ("backward blocking") during a
      second stage of training in which competing cues, but not target cues, were
      presented. These changes in causal judgements were exhibited only by subjects who
      had learned which target and competing cues were paired with one another during
      the first stage of training. These results cannot be explained by the Rescorla
      Wagner (1972) model of associative learning, but they can be explained by the
      revised model of Van Hamme and Wasserman (1994); the revised model assigns non
      zero salience to non-presented target stimuli whose memories or representations
      are retrieved by competing stimuli that had previously been paired with those
      target stimuli.

PMID- 9621839
TI  - Temporal coding in Pavlovian conditioning: Hall-Pearce negative transfer.
AB  - The Hall-Pearce (1979) negative transfer effect in rats was used to examine
      whether temporal relationships are coded as part of the informational content of
      associations that results from CS-US pairings. The transfer effect consists of a
      deficit in conditioned responding following CS-USstrong pairings in Phase 2 that
      results from prior CS-USweak pairings in Phase 1. Using conditioned bar-press
      suppression, we found that gaps of different duration between CS termination and
      US onset in the two training phases resulted in less of a Hall-Pearce negative
      transfer effect than did an equivalent gap in the two training phases. The
      results are discussed with respect to the temporal coding hypothesis (Matzel,
      Held, & Miller, 1988), the Pearce and Hall (1980) model, and Bouton's (1993)
      interference model.

PMID- 9621840
TI  - Reaching into cluttered visual environments: spatial and temporal influences of
      distracting objects.
AB  - Subjects reached for visual target lights in the presence of distractor lights.
      Previous studies (e.g., Tipper, Lortie, & Baylis, 1992) have shown that
      distractors at locations between the starting position of the hand and the target
      location caused greater interference (as indexed by response time) than
      distractors beyond the target. This finding has been attributed to the former
      distractors being in the path of the response to the target, but we provide
      evidence that they interfere more because of their proximity to the starting
      position of the hand (a "proximity-to-hand effect"). Also, distractors located in
      the hemispace ipsilateral to the responding hand caused more interference than
      contralateral distractors (an "ipsilateral effect"). The proximity-to-hand and
      ipsilateral effects were found in both reaction and movement time, suggesting
      that the resolution of the selection problem caused by a distractor could occur
      before or after movement initiation. Further evidence for this suggestion was
      provided by individual differences in movement initiation strategies which were
      predictive of the temporal locus of distractor influence. Errors of touching the
      distractor location also showed proximity-to-hand and ipsilateral effects. We
      discuss applications of these findings to real-world situations in which people
      reach for the wrong object in multiple-object visual displays.

PMID- 9621841
TI  - Increases in intrusion errors and working memory deficit of poor comprehenders.
AB  - This study tests the hypothesis that the ability to inhibit already processed and
      actually irrelevant information could influence performance in the listening span
      test (Daneman & Carpenter, 1980) and have a crucial role in reading
      comprehension. In two experiments, the listening span test and a new working
      memory test were given to two groups of young adults, poor and good
      comprehenders, matched for logical reasoning ability. In Experiment 1, the poor
      comprehenders had a significantly lower performance in the listening span test
      associated to a higher number of intrusions--that is, recalled words that, in
      spite of being in sentence form, were not placed in the last position. In
      Experiment 2, a new working memory test was devised in order to analyse more
      effectively the occurrence of intrusions. Subjects were required to listen to a
      growing series of strings of animal and non-animal words. While listening, they
      had to detect when an animal word occurred, and at the end of each series they
      had to recall the last word of each string. The poor comprehenders obtained a
      significantly lower performance in the memory task and made a higher number of
      intrusions, particularly of animal words.

PMID- 9621842
TI  - Understanding caricatures of faces.
AB  - Lateral caricatures are transformed faces like caricatures but the transformation
      is orthogonal (in the face-space, Valentine, 1991) to the direction of
      caricaturization. It has been reported that lateral caricatures are more
      difficult to recognize than anti-caricatures (Rhodes & Tremewan, 1994). To
      investigate this effect, oblique caricatures (transformed obliquely to
      caricaturing) were generated by morphing between a veridical face and a reference
      face. Two experiments used a forced-choice similarity task to find which images
      are perceived to have the least change from the veridical. An advantage for
      caricatures over anti-caricatures was found, but none was found between oblique
      and anti-caricatures. Performance of theoretical lateral caricatures was
      extrapolated from the oblique caricature data. These lateral caricatures would be
      perceived as more similar to veridical faces than were the anti-caricatures.

PMID- 9621843
TI  - Visual search for a tilted target: tests of spatial uncertainty models.
AB  - We report that spatial cueing of a parafoveal target in the presence of
      distractors enhances orientational acuity for that target. When no distractors
      were present, orientation thresholds were in the range 1-4 degrees. For long
      exposure times, distractors increased threshold by the amount predicted from a
      winner-takes-all spatial uncertainty model. For short (100-msec) exposures
      followed by a random dot mask, the rise in threshold with distractors was
      considerably greater than that predicted from spatial uncertainty. For brief
      exposures the effect of distractors was greater when the target and distractors
      were spatially crowded rather than widely spaced. Adding a tilt to the
      distractors in the opposite direction to the target increased thresholds still
      further. Cueing the target with a spatial pointer decreased the effect of
      distractors, even when they were crowded. We suggest that when attention cannot
      be appropriately focused, discrimination is carried out by a relatively coarse
      texture analyser, which averages over several elements, and that focused
      attention permits the analysis of the target over a smaller area of space.

PMID- 9621844
TI  - Central fixations are inadequately controlled by instructions alone: implications
      for studying cerebral asymmetry.
AB  - A fundamental concern when using visual presentations to study cerebral asymmetry
      is to ensure that stimuli are presented with the same degree of retinal
      eccentricity from a central fixation point in either visual field. However, a
      widely used procedure intended to control fixation location merely instructs
      participants to fixate appropriately without any other means of ensuring that
      central fixations actually occur. We assessed the validity of assuming that
      instructions alone ensure central fixation by using the traditional RVF advantage
      for words and either (a) only instruction to fixate centrally, or (b) eye
      tracking device that ensured central fixation on every trial. Experiments 1 and 2
      found that when only instructions were given, the vast majority of fixations were
      not central, and more occurred to the right of centre than to the left. Moreover,
      the prevalence of non-central fixations was otherwise disguised by the finding
      that both fixation procedures produced similar RVF advantages in overt
      performance. The impact of typical non-central fixations on performance was
      revealed by systematically manipulating fixation location in Experiment 3, where
      deviations in fixation of only 0.25 degrees from centre had a reliable impact on
      visual field effects. Implications of these findings for studies of cerebral
      asymmetry are discussed.

PMID- 9621845
TI  - Sudden cardiac death in the athlete.
AB  - The sudden unexpected death of an athlete is a disturbing and tragic event.
      Sudden cardiac death in the young athlete is caused primarily by cardiomyopathies
      and nonatherosclerotic coronary artery abnormalities; in the mature athlete, the
      most prevalent cause of sudden cardiac death is atherosclerotic coronary disease.
      The job of the emergency physician is to resuscitate those who succumb to
      ventricular dysrhythmias during exercise and to screen patients for potential
      risk of sudden cardiac death when they present with warning symptoms such as
      syncope.

PMID- 9621846
TI  - Clinical differentiation of narrow QRS complex tachycardias.
AB  - Supraventricular tachycardias generally present with narrow QRS complexes and are
      quite commonly seen in the emergency department. Regular narrow QRS complex
      tachycardias occur in all age groups and may be associated with minimal symptoms,
      such as palpitations, or, present with hemodynamic compromise resulting in
      syncope. While history and physical examination are indispensable, they usually
      do not lead to a definitive diagnosis. The diagnosis is made by careful analysis
      of the 12-lead ECG. Therapy is based on hemodynamic assessment and understanding
      of the tachycardia mechanism.

PMID- 9621847
TI  - Clinical approach to wide QRS complex tachycardias.
AB  - Wide QRS complex tachycardia is a frequently encountered arrhythmia in the
      emergency department and presents a diagnostic challenge to the emergency
      physician. The history, physical examination, chest radiograph, and
      electrocardiogram analysis are important in making the correct diagnosis. The
      diagnosis of ventricular tachycardia is supported by, 1) a history of prior
      myocardial infarction or congestive heart failure; 2) a physical examination
      showing cannon A-waves in the jugular venous pulsation or variable heart sounds;
      3) a chest radiograph showing cardiomegaly or evidence of prior cardiac surgery;
      and 4) characteristic ECG features that include AV dissociation, fusion-capture
      beats, QRS concordance, or, typical morphologic features in leads V1 and V6. This
      article presents the diagnostic and therapeutic approaches to wide QRS
      tachycardias.

PMID- 9621848
TI  - Evaluation and management of bradyarrhythmias in the emergency department.
AB  - Bradyarrhythmias may be due to varied causes, although acute myocardial
      infarction, hypoxia, sepsis, and hypothermia should be considered. Emergency
      department therapy consists of treatment of the underlying cause, pharmacologic
      interventions, and temporary pacing. This article provides a detailed discussion
      of the causes and treatment of bradyarrhythmias in the emergency department.

PMID- 9621849
TI  - Evaluation and management of atrial fibrillation in the emergency department.
AB  - AF is the most common sustained cardiac arrhythmia. Recognition and appropriate
      management of AF is important to optimize care of concurrent medical problems and
      prevent long-term consequences. DC cardioversion under sedation should be
      performed in patients with pulmonary edema, angina, or hypotension. Ventricular
      rate control is the first choice in stable patients with rapid ventricular rate.
      Anticoagulation should be considered in all patients with AF duration < 48 hours,
      except for those under 65 years old and having no other risk factors of stroke.
      Recent data imply that early attempts at cardioversion may increase success rates
      and decrease AF recurrence rates. Thus, transesophageal echocardiogram-guided
      early cardioversion may become more widely used.

PMID- 9621850
TI  - Arrhythmias associated with drug toxicity.
AB  - Cardiac arrhythmias may result from poisoning by a variety of agents. Although
      some cardiac disturbances are of limited concern, others occur because of the
      specific cardiac properties of the ingested drugs, and require specific
      antidotes. Clinicians must understand the resultant pathophysiology so that
      therapy is appropriate. This article focuses on drugs that cause ventricular
      arrhythmias and bradyarrhythmias.

PMID- 9621851
TI  - Permanent cardiac pacing.
AB  - Implantation of a permanent pacemaker is the most commonly performed surgical
      operation involving the heart. The modern cardiac pacemaker is a complex device
      that can sense and pace in both the atrium and ventricle. It also modulates the
      pacing rate based on sensed physiologic parameters. This article reviews the
      fundamental principles of pacemaker technology and provides the emergency
      physician with approaches to common pacemaker problems.

PMID- 9621852
TI  - Implantable cardioverter defibrillators.
AB  - Implantable cardioverter defibrillators have proven to be an effective therapy
      for life-threatening ventricular arrhythmias. Given the ever-increasing number of
      patients who have these devices, increasing numbers of patients are likely to
      present to emergency departments with defibrillator-related problems. This
      article discusses normal device function, indications for implantation, and
      technique of implantation. It also focuses on the evaluation and management of
      patients with these devices presenting to the emergency department.

PMID- 9621853
TI  - Dr. Benjamin M. Spock and Mayo.

PMID- 9621854
TI  - Effect of pramipexole in treatment of resistant restless legs syndrome.
AB  - OBJECTIVE: To report the results of an open-label trial with a dopaminergic
      agent, pramipexole, in patients with treatment-resistant restless legs syndrome
      (RLS). MATERIAL AND METHODS: We studied the response to pramipexole in a
      consecutive series of 16 patients with symptomatic RLS who had previously
      experienced failure with other dopaminergic therapies. Patients assessed their
      posttreatment change in symptoms of RLS on a visual analog scale and indicated
      drug-related side effects with use of a checklist. RESULTS: With a mean dose of
      pramipexole of 0.3 mg, most patients reported clinically significant improvement.
      From 2 to 3 months after initiation of pramipexole therapy, nocturnal leg
      restlessness, involuntary leg movements, and insomnia had decreased in 12, 10,
      and 11 patients, respectively. The most frequent adverse effects were fatigue and
      stiffness, which occurred in a third of the patients. Overall, the drug was well
      tolerated. CONCLUSION: On the basis of these findings, we propose that
      pramipexole, a D2 subgroup receptor agonist, is an effective agent for treatment
      of RLS.

PMID- 9621855
TI  - Continent orthotopic urinary diversion in female patients: early Mayo Clinic
      experience.
AB  - OBJECTIVE: To review our initial experience with orthotopic neobladder urinary
      diversion in female patients. MATERIAL AND METHODS: We reviewed the clinical
      characteristics, operative reports, and pathologic results of five female
      patients who underwent radical or simple cystectomy and continent orthotopic
      urinary diversion. Peri-operative morbidity, postoperative daytime and nighttime
      continence, renal function, need for protective pads, and self-catheterization
      were documented. All urodynamic and upper urinary tract imaging studies were
      reviewed. RESULTS: Follow-up has ranged from 9 to 18 months in these initial
      patients. Thus far, all five women have achieved acceptable daytime continence,
      and four of five women have achieved nighttime continence. Only one patient
      augments volitional voiding with intermittent self catheterization. Complications
      consisted of urinary retention in one patient and development of a urinary tract
      and bladder calculus, which necessitated cystolitholapaxy, in another patients.
      Neobladder capacities have ranged from 400 to 600 mL with voided volumes up to
      300 mL. Only one patient has had a substantial residual urine volume (300 mL).
      All upper urinary tract imaging studies have shown stable function, and
      urodynamic studies have revealed high-compliance, large-volume neobladder
      capacities in all patients. CONCLUSION: Bladder replacement pouches designed from
      detubularized bowel are gaining widespread acceptance among urologists and their
      patients. Although these operations have previously been limited to men because
      of concerns about cancer-involved margins and continence after cystectomy in
      female patients, recent advances in the knowledge of female pelvic anatomy and
      neurovascular innervation of the bladder neck and proximal urethra have
      facilitated nerve-preserving radical cystectomy in women that allows continence
      and volitional voiding through the urethra.

PMID- 9621856
TI  - Superior-inferior stability of the shoulder: role of the coracohumeral ligament
      and the rotator interval capsule.
AB  - OBJECTIVE: To study the superior-inferior stabilizing functions of the
      coracohumeral ligament (CHL) and the rotator interval capsule (RIC) with use of a
      material testing machine. MATERIAL AND METHODS: The axial translations of the
      humerus with the superior-inferior translation force of 30 N applied were
      recorded under the following joint capsule conditions: (1) intact, (2) vented,
      (3) the CHL sectioned, and (4) the RIC incised in six cadaver shoulders. The
      order of sectioning was changed for conditions 3 and 4 in six other cadaver
      shoulders. RESULTS: With the arm in internal and neutral rotations, venting the
      capsule significantly increased the superior-inferior translation, which was
      unaffected by further sectioning of the CHL and the RIC. With the arm in external
      rotation, only the CHL contributed significantly to inferior stability, whereas
      both this ligament and the RIC contributed to superior stability to a lesser
      degree. CONCLUSION: The CHL is a stabilizer in superior inferior directions with
      the arm in external rotation, and the intra-articular pressure that is maintained
      by the intact RIC is a stabilizer in superior-inferior directions with the arm in
      internal and neutral rotations. These findings may provide a scientific
      background to support closure of the interval space to stabilize the shoulder and
      may explain part of the superior instability observed in shoulders with rotator
      cuff tears.

PMID- 9621857
TI  - The radiodensity of medications seen on x-ray films.
AB  - OBJECTIVE: To analyze the radiodensity of commonly used medications and determine
      their ability to be seen on plan x-ray films. MATERIAL AND METHODS: Under
      conditions intended to simulate a patient undergoing radiography of the abdomen
      (including the use of a patient-equivalent phantom), 50 prescription and
      nonprescription drugs were tested. Their radiodensities were quantified, and
      their visibility on plain x-ray films was noted. The study drugs were then ranked
      in order of decreasing radiodensity. In addition, we report an illustrative case
      of ingested pills in the stomach that mimicked gallstones, a phenomenon we termed
      "pseudogallstones". RESULTS: In a 71-year-old woman with upper abdominal pain and
      nausea, a presumptive diagnosis of gallstones based on x-ray findings was
      subsequently found to be retained iron tablets. This case prompted our assessment
      of the radiodensity of medications frequently prescribed for elderly patients.
      Although all 50 medications studied were visible on plain x-ray films, a 13-fold
      difference was found in their relative radiodensities. Of the medications
      studied, potassium chloride was the most radiodense, and prednisone was the least
      radiodense. As a group, minerals were the most radiodense of all medications
      studied. CONCLUSION: Numerous commonly prescribed medications in their
      undissolved, undigested state are visible on plain x-ray films, as are mineral
      supplements, which have high radiodensities. At times, the appearance of these
      medications and supplements may be confused with organic pathologic conditions.

PMID- 9621859
TI  - Inpatient treatment of severe nicotine dependence in a patient with
      thromboangiitis obliterans (Buerger's disease).
AB  - Thromboangiitis obliterans (TAO), or Buerger's disease, is an inflammatory,
      occlusive, and nonatherosclerotic vascular disease that most commonly affects
      small and medium-sized arteries and veins. The association between tobacco use
      and the development of TAO is incontestable; however, a substantial number of
      patients with TAO continue to use tobacco despite progression of disease and
      amputation. Herein we describe a patient with advanced TAO whose severe,
      refractory nicotine dependence was successfully treated in a specialized nicotine
      dependence inpatient program. After cessation of smoking, the patient's disease
      stabilized. Inpatient nicotine-dependence treatment may represent an alternative
      for recidivist smokers with severe tobacco-related disease.

PMID- 9621858
TI  - True malignant histiocytosis.
AB  - OBJECTIVE: To attempt to distinguish cases of true malignant histiocytosis from
      the clinical syndromes of so-called malignant histiocytosis with use of recent
      methods. DESIGN: We retrospectively studied the laboratory data and clinical
      course of Mayo patients who had clinical syndromes of so-called malignant
      histiocytosis and reviewed available paraffin-embedded tissue specimens to
      identify the nature of the malignant cells. MATERIAL AND METHODS: After
      elimination of cases of infection-associated hemophagocytic syndrome, we reviewed
      and studied seven cases of so-called malignant histiocytosis in patients who had
      undergone assessment at Mayo Clinic Rochester between 1973 and 1993. We
      identified histiocytes by using current morphologic, cytochemical, and
      immunohistochemical methods. The clonal nature of the malignant cells was
      identified with morphologic, cytogenetic, and molecular genetic studies. RESULTS:
      Only one of the seven cases had a true histiocytic origin. The malignant cells
      were T cells in three other cases (the cells were also CD30+ in two cases), CD30+
      cells only in one case, epithelial cells in one case, and an undetermined cell
      type (stained positively only with antitrypsin) in one case. CONCLUSION: True
      malignant histiocytosis is an exceedingly rare disease, and only a few reports
      have clearly identified the histiocytic origin of the malignant cells.
      Previously, the lack of monoclonal antibodies specific to histiocytes and the
      absence of techniques for performing molecular genetic studies on paraffin
      embedded tissue prevented the study of such cases. With newer techniques cases of
      true malignant histiocytosis can now be identified.

PMID- 9621861
TI  - Erwin Neher--Nobel laureate for studies of cell function.

PMID- 9621860
TI  - Diagnostic value of albumin gene expression in liver tumors: case report and
      review of the literature.
AB  - Management of a solitary liver mass necessitates reliable distinction between
      primary hepatocellular carcinoma and metastatic lesions. The histologic
      differentiation can be difficult even with special stains such as alpha
      fetoprotein, cytokeratin, and carcinoembryonic antigen. Albumin is a specific
      product of hepatocytes, and in situ hybridization to reveal albumin messenger RNA
      (mRNA) is highly specific and sensitive for the diagnosis of primary
      hepatocellular carcinoma. This technique can be used on histopathologic specimens
      and in cytologic diagnosis. Herein we describe a patient with synchronous renal
      and hepatic masses, in whom the distinction had to be made between metastatic
      renal cell carcinoma and two separate primary tumors--one in the liver and one in
      the kidney. In situ hybridization for albumin mRNA proved helpful in making this
      distinction. In addition, we review the literature on the diagnostic use of
      albumin gene expression in liver tumors.

PMID- 9621862
TI  - Vena caval impalement: an unusual lawn mower injury in a child.
AB  - Penetrating injury to the vena cava is a potentially life threatening condition
      that necessitates prompt recognition and immediate treatment. Herein we describe
      a unique lawn mower-related injury in a 4-year-old boy, resulting in the
      impalement of the inferior vena cava by a foreign body projectile. Relevant
      concepts in the management of children with lawn mower injuries are discussed,
      with emphasis on penetrating injury to the inferior vena cava.

PMID- 9621863
TI  - 59-year-old man with right hip pain.

PMID- 9621864
TI  - Use of low-molecular-weight heparin in the treatment of venous thromboembolic
      disease: answers to frequently asked questions. The Thrombophilia Center
      Investigators.
AB  - Low-molecular-weight heparins (LMWHs) represent an important therapeutic advance
      in the treatment of patients with venous thromboembolism. The use of LMWH has
      potential advantages in comparison with the use of standard unfractionated
      heparin (UH), including decreased binding to nonanticoagulant-related plasma
      proteins, greater bioavailability, longer half-life, and lower incidence of the
      heparin-induced thrombocytopenia syndrome. Because of the predictable
      anticoagulant response of LMWH when administered subcutaneously, laboratory
      monitoring is unnecessary, and the drug can be used to treat selected patients
      with venous thromboembolism in outpatient setting. Numerous studies have shown
      that the treatment of venous thromboembolism with LMWH is as safe and effective
      as that with standard UH when both are used appropriately. Allied health
      personnel can easily teach most patients to self-administer LMWH subcutaneously
      for home use. Transition of the treatment regimen to oral warfarin
      anticoagulation necessitates an overlap with heparin (UH or LMWH) for at least 4
      to 5 days, and the international normalized ratio should ideally be 2.0 or higher
      for 2 consecutive days before heparin therapy is discontinued. A practical
      understanding of the pharmacology, risks, and benefits of LMWH in the treatment
      of venous thromboembolism will enhance the primary-care physician's ability to
      care for patients safely and cost-effectively.

PMID- 9621865
TI  - Lung volume reduction surgery for emphysema: out on a limb without a NETT.
AB  - Lung volume reduction surgery (LVRS) has recently been rediscovered and offers
      the potential of improving the quality of life of patients with advanced
      emphysema. In this article, we discuss the historical and contemporary versions
      of LVRS. Although initial enthusiasm has been substantial, existing data seem
      insufficient to demonstrate the safety and efficacy of the procedure in
      comparison with conventional medical therapy. Fundamental questions remain
      regarding the long-term effects of an operation versus medical therapy, the
      optimal selection criteria, the best measures of efficacy, the mechanisms of
      improvement, the cost-effectiveness of the procedure, and the optimal surgical
      technique. Until such questions are answered, advising patients about the best
      management their emphysema will be difficult. The National Emphysema Treatment
      Trial will address many of these issues and should be embraced by both health
      care providers and patients.

PMID- 9621866
TI  - Perioperative neuropathies.
AB  - Neuropathies are infrequent but potentially debilitating complications in
      surgical patients. Although the most common of these affect the peripheral ulnar
      and sciatic nerves, more centrally located sets of nerves such as the brachial
      plexus and lumbosacral nerve roots also can be affected perioperatively.
      Traditionally, these neuropathies have been considered avoidable and associated
      with inappropriate patient positioning intraoperatively. Recent epidemiologic and
      anatomic studies suggest, however, that various factors other than intraoperative
      positioning may contribute to the development of neuropathies. For example, it is
      now clear that a large proportion of surgical patients who subsequently have
      development of ulnar neuropathies are asymptomatic during the first several
      postoperative days. Further delineation of the epidemiology and causes of the
      various perioperative neuropathies should lead to innovative interventions and
      clinical trials of their effectiveness to decrease the frequency and severity of
      these complications in surgical patients.

PMID- 9621867
TI  - Liver transplantation for primary biliary cirrhosis and primary sclerosing
      cholangitis: predicting outcomes with natural history models.
AB  - In patients with primary biliary cirrhosis (PBC) and primary sclerosing
      cholangitis (PSC), risk score models that reflect disease severity have been
      developed and can serve as an objective measurement to assess and evaluate the
      effect of the severity of liver disease on the outcome of liver transplantation.
      Thus, using the established Mayo risk scores for PBC and PSC, one not only can
      estimate survival for the individual patient but can measure disease activity as
      well. Indeed, several studies have suggested that the optimal timing of liver
      transplantation with use of the Mayo PBC model may be an important tool to
      improve survival, decrease morbidity, and decrease overall related costs.
      Likewise, studies in patients with PSC have yielded similar results. This review
      explores how prognostic mathematical survival models for PBC and PSC might be
      applied to individual patients in need of liver transplantation. The following
      question is addressed: How can the timing of liver transplantation be optimized
      to increase survival, decrease postoperative morbidity, and ultimately, decrease
      the overall resource utilization involved in this procedure?

PMID- 9621868
TI  - Contemporary management of the benign obstructive prostate: an overview.

PMID- 9621869
TI  - Pharmacologic therapy for prostatism.
AB  - Although the general approach to management of a sufficient degree of benign
      prostatic hyperplasia in the past was surgical intervention (transurethral
      resection of the prostate), the current availability of effective pharmacologic
      therapy has changed the initial management strategy. At present, two types of
      drugs are available for treatment of prostatism: (1) selective alpha-adrenergic
      blocking agents (terazosin, doxazosin, and tamsulosin) and (2) an inhibitor of
      the 5 alpha-reductase enzyme (finasteride). Pharmacologic blockade of the
      alpha(1)-adrenoceptors is thought to result in relaxation of the smooth muscle in
      the prostate and bladder neck, which reduces urethral resistance, improves
      voiding function, and minimizes the symptoms of prostatism. These effects may be
      noted by the patient within several weeks after initiation of treatment. The
      mechanism of action of finasteride is a blocking of the conversion of
      testosterone to dihydrotestosterone and an associated volume shrinkage of the
      prostate. On the average, a 25% reduction in prostate volume can be achieved, but
      a period of 12 months or longer of finasteride therapy is needed for maximal
      shrinkage and maximal decrease in symptoms of prostatism. The expanding
      population of middle-aged and elderly men with prostatism of moderate severity
      will undoubtedly prompt the development of additional pharmacologic options for
      treatment of prostatism and benign prostatic hyperplasia.

PMID- 9621870
TI  - Current status of transurethral thermotherapy at the Mayo Clinic.
AB  - With the ever-expanding elderly population in the United States, benign prostatic
      hyperplasia (BPH) has become a widespread condition. Although surgical
      intervention (open prostatectomy and transurethral resection of the prostate) was
      the typical management approach for BPH in the past, other options currently
      include drug therapy and transurethral thermotherapy, a minimally invasive
      procedure that involves the targeting of heat deep within the prostate transition
      zone while cooling the surrounding anatomic structures with circulating water.
      Two thermo-therapy-devices--the Prostatron and the T3 transurethral
      thermoablation therapy catheter--have been studied in randomized controlled
      clinical trials at the Mayo Clinic. Both devices were shown to be effective in a
      substantial subset of patients with BPH: symptom scores decreased, peak urinary
      flow rates increased, and total serum prostate-specific antigen levels increased,
      an indication of destruction of adenomatous tissue. All patients were able to
      complete the treatment without the need for general or regional anesthesia, and
      thermotherapy was associated with few postprocedural events. Although this
      therapeutic strategy is currently used selectively in patients with lateral lobe
      prostatic adenoma, improvements in technology and understanding of the
      thermoregulatory properties of the prostate should broaden the application of
      thermotherapy devices in the management of BPH.

PMID- 9621871
TI  - Evidence-based surgery.

PMID- 9621872
TI  - Veterinarians integral in resolving avian influenza incidents, developing
      vaccine.

PMID- 9621873
TI  - What is your diagnosis? Multiple epiphyseal dysplasia of the femoral head,
      proximal humerus and vertebral end plates.

PMID- 9621874
TI  - Animal behavior case of the month. A dog was examined because of profound
      separation anxiety.

PMID- 9621875
TI  - Externship and preceptorship programs--some legal considerations.

PMID- 9621876
TI  - Helpful tips for extralabel drug use: companion animals, minor and exotic
      species, and wildlife.

PMID- 9621877
TI  - Zoonoses and potential zoonoses transmitted by bats.

PMID- 9621878
TI  - Associations between body condition and disease in cats.
AB  - OBJECTIVE: To determine the association between body condition and disease in
      cats. DESIGN: Prospective study. SAMPLE POPULATION: Information on 1,457 cats
      without major illnesses from 27 veterinary hospitals in the northeastern United
      States. PROCEDURE: Cats that had body conditions determined from 1991 to 1992,
      using a set of 6 body condition silhouettes, had their health experiences and
      body conditions assessed for the subsequent 4.5 years. Cats were described by the
      following 6 body conditions: cachectic, lean, optimally lean, optimal weight,
      heavy, and obese. Data obtained from medical records and owner interviews were
      collected, using standard forms. Associations between body condition and specific
      diseases were analyzed. Findings in cats with body conditions other than optimal
      were compared with findings in cats with optimal body condition. RESULTS:
      Compared with optimal weight cats, heavy cats were 2.9 times as likely to be
      taken to veterinarians because of lameness not associated with cat bite
      abscesses. Obese cats were also 3.9 times as likely to develop diabetes mellitus,
      2.3 times as likely to develop nonallergic skin conditions, and 4.9 times as
      likely to develop lameness requiring veterinary care. Cats considered thin
      (cachectic and lean) were 1.7 times as likely to be presented to veterinary
      hospitals for diarrhea. CLINICAL IMPLICATIONS: Results of this study substantiate
      reports of health risks associated with excess body weight in cats. Efforts to
      reduce weight in heavy and obese cats can lead to reduced risks of diabetes
      mellitus, lameness (presumably related to osteoarthritis and soft-tissue
      injuries), and skin problems unrelated to allergies. Cachectic and lean cats are
      more likely to have diarrhea that is not associated with a definitive diagnosis.

PMID- 9621879
TI  - Prevalence of attenuated wavy fibers in myocardium of dogs with dilated
      cardiomyopathy.
AB  - OBJECTIVE: To determine the prevalence of attenuated wavy fibers in the
      myocardium of dogs with and without dilated cardiomyopathy (DCM). DESIGN:
      Prevalence survey. ANIMALS: 70 dogs clinically suspected to have DCM (ie,
      fractional shortening < 25%, absence of echocardiographic lesions other than
      chamber dilatation, and radiographic or postmortem evidence of congestive heart
      failure) and 147 dogs with chronic valvular disease (n = 60), congenital heart
      disease (49), myocardial infarcts (23), myocarditis (8), or endocarditis (7).
      PROCEDURE: Echocardiography and electrocardiography were performed, and thoracic
      radiographs were obtained with dogs in left lateral recumbency. Necropsy
      specimens were examined for attenuated wavy fibers (ie, myocardial cells < 6
      microns in diameter with a wavy appearance). RESULTS: 65 of 70 dogs clinically
      suspected to have DCM were confirmed to have the disease on postmortem
      examination, and 64 of 65 had attenuated wavy fibers. The remaining 5 dogs were
      found during postmortem examination to have heart disease other than DCM, and
      none had attenuated wavy fibers. Only 1 of 147 dogs with heart disease other than
      DCM had attenuated wavy fibers. CLINICAL IMPLICATIONS: Findings suggest that
      histologic examination for attenuated wavy fibers may be a useful postmortem test
      for DCM in dogs. The diagnosis was confirmed in 65 of 70 dogs suspected to have
      DCM on the basis of standard clinical criteria.

PMID- 9621880
TI  - Examination for heat-labile, heat-stable, and Shiga-like toxins and for the eaeA
      gene in Escherichia coli isolates obtained from dogs dying with diarrhea: 122
      cases (1992-1996).
AB  - OBJECTIVE: To examine Escherichia coli isolates obtained from dogs dying with
      diarrhea for heat-labile, heat-stable, and Shiga-like toxins and for the eaeA
      gene, which is associated with attaching and effacing lesions. DESIGN:
      Retrospective study. ANIMALS: 122 dogs. PROCEDURE: E coli isolates were tested by
      means of dot-blot hybridization of DNA extracts of cultured bacteria. Medical
      records of dogs from which E coli isolates with virulence genes had been isolated
      were examined, and histologic findings and evidence of intercurrent bacterial and
      viral infections were recorded. RESULTS: None of the E coli isolates obtained
      from these dogs produced heat-labile, heat-stable, or Shiga-like toxins; however,
      E coli isolates from 44 of 122 dogs were found to have the eaeA gene.
      Histologically, multifocal bacterial adherence to the epithelium and epithelial
      necrosis and detachment were seen in colonic specimens from 20 of 44 (45%) dogs.
      Escherichia coli was the sole pathogen identified in 15 of 44 (34%) dogs.
      Intercurrent pathogens, including canine parvovirus (n = 19), Clostridium
      perfringens (8), rotavirus (5), hookworms (3), coccidia (3), and Salmonella agona
      (1), were identified in the remaining 29 (66%) dogs. CLINICAL IMPLICATIONS:
      Attaching and effacing E coli can be a primary or secondary pathogen in dogs with
      diarrhea. Antibiotic treatment is indicated in dogs with diarrhea because of the
      possibility that it is primarily bacterial in origin and because, even if it is
      primarily viral in origin, there may be secondary bacterial infection.

PMID- 9621881
TI  - Results of postmortem examination of psittacine birds with cardiac disease: 26
      cases (1991-1995).
AB  - OBJECTIVE: To characterize prevalence and type of cardiac disease evident in
      psittacine birds during postmortem examination. DESIGN: Retrospective study.
      ANIMALS: 26 psittacine birds with gross and histologic evidence of cardiac
      disease. PROCEDURE: Records of postmortem examinations of psittacine birds
      necropsied during a 4-year period were reviewed. Data on gross and histologic
      evidence of cardiac disease were analyzed. Birds identified included those in
      which congestive heart failure (CHF) was considered the primary cause of death
      and those in which substantial cardiac disease was evident, despite a lack of
      postmortem findings supportive of CHF. RESULTS: Of 269 psittacine birds
      necropsied, 26 (9.7%) had evidence of cardiac disease. In 15 (58%) birds with
      cardiac disease, changes consistent with CHF were evident and were sufficiently
      severe as to be considered the cause of death. The remaining 11 birds had cardiac
      lesions secondary to other systemic diseases; cardiac lesions were considered to
      be an incidental finding in these birds, and CHF was not evident. Of the 15 birds
      with CHF, 10 had evidence of right ventricular or biventricular failure, whereas
      only 5 had evidence of left ventricular failure. CLINICAL IMPLICATIONS:
      Prevalence of cardiac disease in the psittacine birds reported here was similar
      to that seen clinically in other companion animals. The high incidence of right
      ventricular or biventricular heart failure in psittacine birds was similar to
      that for poultry in which lesions of right-sided heart failure predominate.

PMID- 9621882
TI  - Association of sex of fetus, sire, month of conception, or year of foaling with
      duration of gestation in standardbred mares.
AB  - OBJECTIVE: To determine whether sex of fetus, sire, month of conception, or year
      of foaling was associated with duration of gestation in mares. DESIGN:
      Epidemiologic retrospective cohort study. ANIMALS: 500 foalings for 296
      Standardbred mares. PROCEDURE: Data for reproductive events from 1986 to 1992
      were analyzed. Analyses were conducted to determine whether duration of gestation
      was associated with sex of fetus, sire, month of conception, or year of foaling.
      RESULTS: Mean duration of gestation was 343.3 days and was significantly greater
      for colt fetuses (344.4 days) than for filly fetuses (342.2 days). Sire was
      associated with duration of gestation; gestation after mating with certain sires
      was consistently less than 340 days in duration, whereas duration after mating
      with other sires was consistently more than 350 days. Duration of gestation was
      associated with month of conception, decreasing by about 2.5 d/mo for mares
      conceiving later during the breeding season. CLINICAL IMPLICATIONS: Duration of
      gestation is affected by mating to specific sires and by month of conception.
      Stallions associated with exceptionally prolonged gestations might be used to
      breed mares early in the breeding season, whereas stallions associated with
      shorter gestations might be desirable for mares bred later in the breeding
      season. Preparations for impending parturition should be more effective and
      efficient with improved information on expected date of parturition.

PMID- 9621883
TI  - Randomized controlled trial of effects of Escherichia coli antiserum on serum
      immunoglobulin G concentrations and morbidity and mortality rates in foals.
AB  - OBJECTIVE: To determine whether administration of commercially available
      Escherichia coli antiserum to neonatal foals would affect serum IgG concentration
      or morbidity and mortality rates during the first 60 days of life. DESIGN:
      Randomized controlled trial. ANIMALS: 271 neonatal foals on 4 well-managed farms.
      PROCEDURE: Foals were randomly assigned to a treatment or control group. All
      foals were allowed to suckle colostrum normally. In addition, treatment-group
      foals were given E coli antiserum (10 micromilligrams) orally between 0 and 8
      hours after birth. Serum samples were obtained between 18 and 36 hours after
      birth, and serum IgG concentration was determined. Foals were monitored for the
      first 60 days after birth, and causes of disease or death were recorded. RESULTS:
      Groups did not differ significantly in regard to breed, sex, month of birth,
      season of birth, age of dams, parity of dams, duration of gestation, or specific
      gravity of colostrum before suckling. In addition, groups did not differ
      significantly in regard to mean serum IgG concentration, prevalence of complete
      or partial failure of passive transfer of immunity, frequency or causes of
      disease, or frequency of death from infectious causes. CLINICAL IMPLICATIONS: In
      this group of foals on well-managed farms, administration of E coli antiserum did
      not alter serum IgG concentrations or morbidity and mortality rates during the
      first 60 days of life.

PMID- 9621884
TI  - Enterocolitis associated with Clostridium perfringens infection in neonatal
      foals: 54 cases (1988-1997).
AB  - OBJECTIVE: To identify clinical signs, physical examination findings, results of
      diagnostic tests, treatments administered, and clinical outcome of neonatal foals
      with enterocolitis associated with Clostridium perfringens infection. DESIGN:
      Retrospective study. ANIMALS: 54 neonatal foals. RESULTS: Most foals had acute
      onset of obtunded mentation, colic, or diarrhea and developed leukopenia,
      neutropenia, an abnormally high number of band neutrophils, toxic WBC, and
      hypoproteinemia within 24 hours after admission, despite high serum IgG
      concentrations (> 800 mg/dl). Abdominocentesis and abdominal radiography of some
      foals revealed exudative peritonitis and gaseous distention of the small and
      large intestine, respectively. Cytologic examination of feces revealed spores or
      gram-positive rods in 8 of 10 foals. The most common genotypes of C perfringens
      isolates were type A and C, alone or in combination. Treatment did not alter
      mortality rate for most foals that had a positive culture for C perfringens type
      C. Of 54 foals, 29 (54%) that had C perfringens-associated enterocolitis died.
      Foals that had a culture that yielded C perfringens had higher sepsis scores, IgG
      concentrations, and mortality rates, compared with the overall hospital
      population of neonatal foals. CLINICAL IMPLICATIONS: Foals less than 7 days old
      that have enterocolitis associated with C perfringens infections, especially type
      C, have a guarded prognosis. Cytologic examination of feces to determine spore
      counts and detect rods may be a means for early identification of C perfringens
      infections. Polymerase chain reaction assays to determine genotype are important
      for designing preventive treatment regimens.

PMID- 9621885
TI  - Longitudinal fractures of the condyles of the third metacarpal and metatarsal
      bones in racehorses: 224 cases (1986-1995).
AB  - OBJECTIVE: To determine type, distribution, and radiographic appearance of
      condylar fractures of the third metacarpal bone (MC-3) or third metatarsal bone
      (MT-3) in Thoroughbreds (TB), Standardbreds (SB), and Arabians, to assess long
      term outcome of horses in which fractures were repaired surgically, and to
      identify variables associated with prognosis for return to racing. DESIGN:
      Retrospective study. ANIMALS: 224 horses with 233 fractures. PROCEDURE: Medical
      records and radiographs obtained before and after treatment were reviewed. Racing
      performance before and after treatment was determined by reviewing race records.
      RESULTS: TB were overrepresented and SB were underrepresented, compared with the
      hospital population. Thoroughbreds had significantly more lateral condylar
      fractures and significantly more forelimb fractures than did SB. Thoroughbreds
      were less likely to race after treatment if they had complete, rather than
      incomplete, lateral condylar fracture or had concurrent proximal sesamoid bone
      fracture. Convalescent time for TB with medial condylar fractures of MT-3 was
      significantly longer than that for TB with lateral condylar fractures of MT-3.
      CLINICAL IMPLICATIONS: Horses with condylar fractures of MC-3 and MT-3 that had
      minimal pathologic changes in the involved joint had a favorable prognosis for
      returning to racing after surgical treatment. Prognosis for horses with complete
      condylar fractures, particularly those with substantial pathologic changes in the
      involved joint, was worse.

PMID- 9621886
TI  - Evaluation of a commercially available vaccine against Corynebacterium
      pseudotuberculosis for use in sheep.
AB  - OBJECTIVE: To evaluate the efficacy of a commercially available bacterin-toxoid
      vaccine for preventing Corynebacterium pseudotuberculosis-induced abscesses in
      sheep. DESIGN: Prospective randomized controlled trial. ANIMALS: 31 mixed-breed
      sheep seronegative for C pseudotuberculosis. PROCEDURE: Sheep were randomly
      assigned to vaccinate (n = 20) or nonvaccinate (11; control) groups. Sheep in the
      vaccinate group received 2 doses of serial A or serial B bacterin-toxoid vaccine
      at 4-week intervals. Serologic testing was conducted after vaccination to
      document an antibody response to vaccination. All sheep were challenge inoculated
      with virulent C pseudotuberculosis organisms 32 weeks after the second
      vaccination. Twenty weeks after challenge inoculation, all sheep were examined
      for external and internal abscesses secondary to C pseudotuberculosis infection.
      RESULTS: Vaccinated sheep developed an antibody response to both components of
      the vaccine, as measured by use of ELISA tests. After challenge inoculation,
      vaccinated sheep had significantly less external, internal, and total abscesses
      than control sheep. CLINICAL IMPLICATIONS: Vaccination of sheep with a
      commercially available bacterin-toxoid against C pseudotuberculosis could
      substantially decrease the prevalence and number of abscesses that form secondary
      to C pseudotuberculosis infection.

PMID- 9621887
TI  - Alterations in acid-base balance and serum electrolyte concentrations in cattle:
      632 cases (1984-1994).
AB  - OBJECTIVE: To determine typical alterations in acid-base balance and serum
      electrolyte concentrations in cattle grouped on the basis of age, breed type,
      hydration status, clinical signs, and underlying disease. DESIGN: Retrospective
      study. ANIMALS: 632 cattle. PROCEDURE: Information on blood pH, PVO2, PVCO2, HCO3
      concentration, and base excess (BE) as well as serum or plasma sodium, potassium,
      chloride, and total carbon dioxide concentrations was obtained. Values for calves
      (ie, cattle < 1 month old) were compared with values for cattle > or = 1 month
      old. Within each age-group, values were compared for cattle grouped on the basis
      of breed type, previous treatment, and hydration status. Proportions of cattle
      with various disorders for which values were within, greater than, or less than
      reference ranges were determined. RESULTS: BE, pH, and HCO3- concentration were
      significantly higher and PVCO2 and sodium, potassium, and chloride concentrations
      were significantly lower among cattle > or = 1 month old than calves. Base excess
      and HCO3- concentration were significantly lower among dairy than beef calves.
      Sodium and potassium concentrations were significantly lower among dairy than
      beef cattle > or = 1 month old. A higher proportion of cattle that did not
      survive had a high anion gap than cattle that did survive. Sodium, potassium, and
      chloride concentrations were significantly lower among dehydrated cattle than
      cattle that were not dehydrated. CLINICAL IMPLICATIONS: Because certain
      alterations were consistently found in some groups of cattle, it may be possible
      to make reasonable predictions of alterations in acid-base balance and serum
      electrolyte concentrations when laboratory evaluations are not available.

PMID- 9621888
TI  - Patellar tendon rupture in five deer.
AB  - Acute unilateral or bilateral rupture of the patellar tendon was diagnosed in 5
      aged obese female Pere David's deer housed at a zoological park. Rupture occurred
      after an episode of sudden exertion in 4 of 5 deer. Fragmentation, degeneration,
      necrosis, and mineralization of ruptured patellar tendon fibers were found on
      histologic examination. Similar changes were often seen in intact contralateral
      tendons that did not have gross lesions. Patellar tendon rupture in humans is
      associated with concurrent systemic disease, such as systemic lupus
      erythematosus, rheumatoid arthritis, or chronic renal failure. Without evidence
      of underlying systemic disease, spontaneous patellar tendon rupture in deer can
      be considered a sequela to age-related tendinous degeneration compounded by
      sudden exertion and chronic overload attributable to obesity.

PMID- 9621889
TI  - Bone regeneration by implantation of purified, culture-expanded human mesenchymal
      stem cells.
AB  - Bone marrow contains a population of rare progenitor cells capable of
      differentiating into bone, cartilage, tendon, and other connective tissues. These
      cells, referred to as mesenchymal stem cells, can be purified and culture
      expanded from animals and humans and have been shown to regenerate functional
      tissue when delivered to the site of musculoskeletal defects in experimental
      animals. To test the ability of purified human mesenchymal stem cells to heal a
      clinically significant bone defect, mesenchymal stem cells isolated from normal
      human bone marrow were culture-expanded, loaded onto a ceramic carrier, and
      implanted into critical-sized segmental defects in the femurs of adult athymic
      rats. For comparison, cell-free ceramics were implanted in the contralateral
      limb. The animals were euthanized at 4, 8, or 12 weeks, and healing bone defects
      were compared by high-resolution radiography, immunohistochemistry, quantitative
      histomorphometry, and biomechanical testing. In mesenchymal stem cell-loaded
      samples, radiographic and histologic evidence of new bone was apparent by 8 weeks
      and histomorphometry demonstrated increasing bone formation through 12 weeks.
      Biomechanical evaluation confirmed that femurs implanted with mesenchymal stem
      cell-loaded ceramics were significantly stronger than those that received cell
      free ceramics. These studies demonstrate that human mesenchymal stem cells can
      regenerate bone in a clinically significant osseous defect and may therefore
      provide an alternative to autogenous bone grafts.

PMID- 9621890
TI  - Fatigue of bone and bones: an analysis based on stressed volume.
AB  - The measured fatigue strength of a material can be affected by specimen
      size:tests using a large stressed volume may show a low fatigue strength due to
      the increased probability of finding weak regions. A Weibull analysis revealed an
      important size effect in bone and predicted this effect with an accuracy of 12%.
      This approach also explained apparent inconsistencies in the published data and
      made it possible to separate and quantify the effects of frequency, loading mode,
      and material source. The effect of frequency is the same for human and bovine
      bone, and the differences between different types of loading (tension,
      compression, and bending) are small (maximum: 12%). By extrapolating to the
      volume of whole bones, it is concluded that large bones will have a fatigue
      strength much lower, by a factor of 2-3, than that measured by conventional
      tests. Failure within 10(5) cycles is expected to occur at cyclic stresses of 23
      30 MPa in human long bones and of 32-43 MPa in bovine bones. Repair is therefore
      needed to prevent failure at physiological stress levels.

PMID- 9621891
TI  - Osteoblast cytoskeletal modulation in response to mechanical strain in vitro.
AB  - The structural integrity of microfilaments has been shown to be necessary for the
      signal transduction of mechanical stimuli within osteoblasts. Qualitative and
      quantitative changes within the cytoskeleton of osteoblasts may therefore be
      crucial components of the signal transduction processes of these cells in
      response to mechanical stimulation. Avian osteoblasts were strained with a device
      that deforms a flexible, cell-laden membrane at a defined frequency and intensity
      in a uniform biaxial manner. We examined the effects of mechanical strain on the
      accumulation of protein and the expression of the major cytoskeletal elements and
      specific integrin-binding (arginine-glycine-aspartic acid) proteins of these
      cells. Mechanical strain increased the level of total extracellular matrix
      accumulated fibronectin by approximately 150% and decreased that of osteopontin
      by approximately 60% but had no quantifiable effect on the accumulation of beta1
      integrin subunit or collagen type I. An examination of the major elements of the
      cytoskeleton demonstrated that neither the level of actin nor that of the
      intermediate filament protein vimentin changed; however, the amount of tubulin
      decreased by approximately 75% and the amount of vinculin, a major protein of
      focal adhesion complexes, increased by approximately 250%. An analysis of protein
      synthesis by two-dimensional gel electrophoresis of [35S]methionine-labeled
      cytoskeletal proteins demonstrated that the changes in the accumulation of
      vinculin and tubulin resulted from their altered synthesis. Messenger RNA
      analysis confirmed that the changes in accumulation and protein synthesis
      observed for vinculin, fibronectin, and osteopontin were controlled at a
      pretranslational level. Immunofluorescent microscopy demonstrated that mechanical
      strain led to increased formation and thickening of actin stress fibers, with a
      commensurate dissociation in microtubules and a clear increase in levels of
      vinculin at the peripheral edges of the cells. In conclusion, the elevated rate
      of synthesis and the increased accumulation of vinculin and fibronectin, as well
      as the increase in the number and size of stress fibers and focal adhesion
      complexes, suggest that mechanical strain leads to a coordinated change both in
      the cytoskeleton and in extracellular matrix proteins that will facilitate
      tighter adhesion of an osteoblast to its extracellular matrix.

PMID- 9621892
TI  - In vitro differentiation of chick embryo bone marrow stromal cells into
      cartilaginous and bone-like tissues.
AB  - Bone marrow stromal cells, progenitor cells involved in repair of bone and
      cartilage, can potentially provide a source for autologous skeletal tissue
      engineering. We investigated which factors were required to induce in vitro
      differentiation of avian bone marrow stromal cells into three-dimensional
      cartilaginous and bone-like tissues. Bone marrow stromal cells from embryonic
      chicks were expanded in monolayers, seeded onto biodegradable polyglycolic acid
      scaffolds, and cultured for 4 weeks in orbitally mixed Petri dishes. Cell-polymer
      constructs developed an organized extracellular matrix containing
      glycosaminoglycans and collagen, whereas control bone marrow stromal cell pellet
      cultures were smaller and consisted predominantly of fibrous tissue. Bone marrow
      stromal cells expanded with fibroblast growth factor-2 and seeded onto polymer
      scaffolds formed highly homogeneous three-dimensional tissues that contained
      cartilage-specific molecular markers and had biochemical compositions comparable
      with avian epiphyseal cartilage. When cell-polymer constructs were cultured in
      the presence of beta-glycerophosphate and dexamethasone, the extracellular matrix
      mineralized and bone-specific proteins were expressed. Our work shows that cell
      expansion in the presence of fibroblast growth factor-2 and cultivation on a
      three-dimensional polymer scaffold allows differentiation of chick bone marrow
      stromal cells into three-dimensional cartilaginous tissues. In the in vitro
      system studied, the same population could be selectively induced to regenerate
      either cartilaginous or bone-like tissue.

PMID- 9621893
TI  - Effect of cooling on cutaneous microvascular adrenoceptors in vivo in the rabbit
      ear.
AB  - Previous studies have suggested that moderate cooling increases the
      responsiveness of vascular alpha2-adrenoceptors. However, limited information is
      available documenting the influence of temperature changes on adrenoceptor
      responses in the microvasculature of thermoregulatory organs (e.g., the human
      digit and the rabbit ear) subjected to a wide range of temperatures. In the
      present study, the effect of local cooling (24 degrees C) on cutaneous
      microvascular adrenoceptors in the ear was observed in vivo in male New Zealand
      White rabbits (total: 66 ears). The rabbit ear was studied in a temperature
      controlled tissue bath; the ear preparation was pretreated with terazosin (an
      alpha1-adrenoceptor antagonist) (10(-5) M) or a combination of terazosin (10(-5)
      M) and propranolol (a beta-adrenoceptor antagonist) (10(-6) M). The microvascular
      diameter responses of the ear to norepinephrine (10(-11)-10(-4) M) then were
      determined at 24 or 34 degrees C, respectively, to determine the influences of
      low temperature on adrenoceptor responses to norepinephrine stimulation. The
      results demonstrated that low concentrations of norepinephrine induced
      vasodilation in arterioles and arteriovenous anastomoses. This vasodilation was
      followed by vasoconstriction with an increased concentration of norepinephrine in
      animals with alpha1-adrenergic blockade at 34 degrees C. Moderate tissue cooling
      increased the microvascular maximal response of the rabbit ear to norepinephrine
      and abolished the vasodilatation induced by a low concentration of
      norepinephrine. There was no significant difference in the microvascular response
      to norepinephrine between the two temperature conditions after simultaneous
      blockade of alpha1-adrenoceptors and beta-adrenoceptors. Data from the present
      study indicate that moderate cooling does not enhance the responsiveness of
      alpha2-adrenoceptors to norepinephrine. In contrast, cooling reduced the beta
      adrenergic activity of arterioles and arteriovenous anastomoses after
      norepinephrine stimulation.

PMID- 9621894
TI  - Correlation between biomechanical and structural changes during the regeneration
      of skeletal muscle after laceration injury.
AB  - A standardized and reliable model for muscle laceration injuries was developed.
      The biomechanical and morphological changes during the process of muscle repair
      after injury were analysed, and the reproducibility of the methods was evaluated.
      The soleus muscles of Sprague-Dawley rats were completely transected and were
      allowed to heal for 5, 7, 10, 14, 21, 28, or 56 days, when the muscles either
      were pulled to failure to measure different parameters of tensile strength or
      were removed for morphological analysis. During the repair process, the
      regenerating myofibers penetrated into the connective-tissue scar and formed new
      myotendinous junctions, thus restoring the functional continuity across the
      muscle stumps. The muscle atrophied significantly during the recovery period.
      Mechanical failure occurred in the scar until day 10, and thereafter it occurred
      within myofibers. Until day 10, the failure load, strain, and specific energy
      increased to as much as 46, 59, and 36% of the control level, respectively;
      thereafter, there were only minor changes. Stress (tensile strength per cross
      sectional area) reached 86% of the control level by day 21 and further increased
      to as much as 96% of the control level until day 56. These results indicate that
      the scar becomes stronger than muscle within 14 days; thereafter, the weakest
      point is the atrophic muscle. The fact that the stress value was most rapidly
      normalized suggests that, qualitatively, the regenerated muscle had virtually
      regained its pretrauma strength by day 56 and that the low values of failure
      load, strain, and specific energy were mainly due to atrophy of the muscle. Thus,
      further increase in the tensile strength of the regenerated muscle-tendon unit
      may require active exercise to reverse muscle atrophy.

PMID- 9621895
TI  - Expression of a stable articular cartilage phenotype without evidence of
      hypertrophy by adult human articular chondrocytes in vitro.
AB  - Chondrocytes that were isolated from adult human articular cartilage changed
      phenotype during monolayer tissue culture, as characterized by a fibroblastic
      morphology and cellular proliferation. Increased proliferation was accompanied by
      downregulation of the cartilage-specific extracellular matrix proteoglycan,
      aggrecan, by cessation of type-II collagen expression, and by upregulation of
      type-I collagen and versican. This phenomenon observed in monolayer was
      reversible after the transfer of cells to a suspension culture system. The
      transfer of chondrocytes to suspension culture in alginate beads resulted in the
      rapid upregulation of aggrecan and type-II collagen and the downregulation of
      expression of versican and type-I collagen. Type-X collagen and osteopontin,
      markers of chondrocyte hypertrophy and commitment to endochondral ossification,
      were not expressed by adult articular chondrocytes cultured in alginate, even
      after 5 months. In contrast, type-X collagen was expressed within 2 weeks in a
      population of cells derived from a fetal growth plate. The inability of adult
      articular chondrocytes to express markers of chondrocyte hypertrophy has
      underscored the fundamental distinction between the differentiation pathways that
      lead to articular cartilage or to bone. Adult articular chondrocytes expressed
      only hyaline articular cartilage markers without evidence of hypertrophy.

PMID- 9621896
TI  - Adenosine 5'-triphosphate, uridine 5'-triphosphate, bradykinin, and
      lysophosphatidic acid induce different patterns of calcium responses by human
      articular chondrocytes.
AB  - Small calcium-mobilizing inflammatory mediators have been implicated in joint
      pathology. Here we demonstrate that bradykinin, adenosine 5'-triphosphate,
      uridine 5'-triphosphate, and lysophosphatidic acid raise the intracellular
      calcium concentration ([Ca2+]i) in human articular chondrocytes. Heterologous
      cross-desensitization experiments showed that the uridine 5'-triphosphate
      response was abolished by prior treatment with adenosine 5'-triphosphate and,
      conversely, that the adenosine 5'-triphosphate response was abolished by prior
      treatment with uridine 5'-triphosphate; this indicated competition for the same
      receptor site, whereas bradykinin and lysophosphatidic acid did not compete with
      other ligands. Pretreatment with thapsigargin abolished ligand-mediated Ca2+
      responses but not vice versa; this confirmed that Ca2+ release occurred from
      intracellular stores. Single-cell analysis of Fura-2 acetoxymethyl ester loaded
      chondrocytes showed mediator-dependent patterns of oscillatory Ca2+ changes in a
      subset of cells when challenged with submaximal concentrations of bradykinin,
      adenosine 5'-triphosphate, or uridine 5'-triphosphate in the presence of
      extracellular Ca2+. However, no oscillatory responses were seen after a challenge
      with lysophosphatidic acid. Therefore, although a number of different Ca2+
      mobilizing ligands activate chondrocytes, the differences that occur in the
      temporal patterning of Ca2+ responses may result in unique mediator-dependent
      changes in cellular activity.

PMID- 9621897
TI  - Chondrocytes in culture produce a mechanically functional tissue.
AB  - A mechanically testable tissue was grown in vitro from rabbit chondrocytes that
      were initially plated at high density (approximately 80,000 cells/cm2). The DNA,
      collagen, and proteoglycan content, as well as the tissue thickness, tensile
      stiffness, and synthesis rates, were measured at 4, 6, and 8 weeks. The
      biochemical properties were similar to those for immature cartilage, with
      predominantly type-II collagen produced; this indicated that the cells retained
      their chondrocytic phenotype. The tissue formed a coherent mechanical layer with
      testable tensile stiffness as early as 4 weeks. The tensile elastic modulus
      reached 1.3 MPa at 8 weeks, which is in the range of values for native cartilage
      from the midzone. Collagen density was approximately 24 mg/ml at 8 weeks, which
      is about one-half the value for native cartilage, and the collagen fibril
      diameters were smaller. Chondrocytes in culture responded to culture conditions
      and were stimulated by cytokine interleukin-1beta. When culture conditions were
      varied to RPMI nutrient medium with lower fetal bovine serum and higher ascorbic
      acid concentrations, the thickness decreased and the modulus increased
      significantly. Interleukin-1beta, added to the 8-week culture for 2 weeks, caused
      a decrease of 60% in thickness, a decrease of 81% in proteoglycan content, and a
      decrease of 31% in collagen content; this is similar to the response of cartilage
      explants to interleukin-1beta. This cartilage analog may be useful as a model
      system to study structure-function relationships in cartilage or as cartilage
      replacement tissue.

PMID- 9621898
TI  - Exposure of cartilage to a fibronectin fragment amplifies catabolic processes
      while also enhancing anabolic processes to limit damage.
AB  - The addition of fibronectin fragments to cultured cartilage causes an initial
      suppression of proteoglycan synthesis, induction of matrix metalloproteinases,
      and resultant decrease in proteoglycan content by about 50% during the first few
      days in culture. Because the proteoglycan loss appears to be limited, we
      investigated whether the fibronectin fragments induce anabolic responses that
      might counter the damage. The effects of various lengths of exposure of cultured
      cartilage to the fibronectin fragment on proteoglycan content, proteoglycan
      synthesis rates, stromelysin-1 release, and tumor necrosis factor-alpha,
      interleukin-1alpha, and interleukin-6 release were investigated. The results
      showed that about 7 days of exposure of cultured cartilage to the fibronectin
      fragment was required for maximal cytokine release, proteoglycan depletion, and
      stromelysin-1 release. However, nearly maximal suppression of proteoglycan
      synthesis occurred within 1 day of the addition of the fibronectin fragment and,
      after its removal, the rates increased to supernormal levels. Decreasing exposure
      to 3 days caused only a small decrease in cartilage proteoglycan content,
      although stromelysin-1 release still occurred. Decreasing exposure to 1 day
      caused an immediate increase in proteoglycan synthesis and an increase to
      supernormal proteoglycan contents. The effect of first treating cartilage with
      the fibronectin fragment for various periods and then allowing a recovery was to
      make the cartilage more resistant to secondary exposures. This study shows that
      cartilage damage can be caused by short exposures to the fibronectin fragment and
      that exposures either optimal or suboptimal for damage additionally amplify
      anabolic processes to make the cartilage resistant to further damage and, thus,
      condition it against pending amplification of damage.

PMID- 9621899
TI  - Bone morphogenetic protein-7 in growth-plate chondrocytes: regulation by retinoic
      acid is dependent on the stage of chondrocyte maturation.
AB  - Although the bone morphogenetic proteins stimulate chondrogenesis, little is
      known regarding their expression and regulation in growth-plate chondrocytes. The
      expression of bone morphogenetic protein-7 was examined in chick growth-plate
      chondrocyte cultures. Low basal levels of bone morphogenetic protein-7 mRNA and
      protein expression were stimulated by increasing doses of all-trans retinoic
      acid, a metabolite of vitamin A. The addition of 10 microM retinoic acid resulted
      in approximately a 6-fold increase in bone morphogenetic protein-7 mRNA levels.
      In contrast, other growth regulators, including basic fibroblast growth factor,
      transforming growth factor-beta, vitamin D, bone morphogenetic protein-6, bone
      morphogenetic protein-7, and parathyroid hormone-related peptide, did not alter
      bone morphogenetic protein-7 transcript levels. The increase in bone
      morphogenetic protein-7 transcripts, although present at 6 hours, was maximal
      following a 12-hour exposure to retinoic acid. Retinoic acid induction of bone
      morphogenetic protein-7 transcript levels was dependent on protein synthesis
      because the induction could be blocked by cyclohexamide. In maturationally
      distinct subpopulations of chondrocytes separated by countercurrent centrifugal
      elutriation, retinoic acid markedly induced bone morphogenetic protein-7 mRNA
      levels in the least differentiated chondrocytes but had no effect in the most
      terminally differentiated hypertrophic chondrocytes. Immunohistochemical
      localization of bone morphogenetic protein-7 demonstrates its expression
      throughout the developing and adolescent growth plate consistent with the
      constitutive pattern of expression seen in isolated chondrocytes. The addition of
      exogenous bone morphogenetic protein-7 to chondrocyte cultures stimulated
      maturation in undifferentiated chondrocyte populations. The data support a role
      for bone morphogenetic protein-7 as an autocrine regulator of chondrocyte
      maturation in the growth plate. Regulation of bone morphogenetic protein-7 by
      retinoic acid may be important in normal growth and development as well as in
      pathologic conditions of an excess or deficiency of vitamin A.

PMID- 9621900
TI  - Biomechanical analysis of limited intercarpal fusion for the treatment of
      Kienbock's disease: a three-dimensional theoretical study.
AB  - Although several types of intercarpal fusion have been advocated for the
      treatment of Kienbock's disease, the clinical outcome of each procedure is still
      inconclusive. The joint load and ligament tension based on a three-dimensional
      model were measured to determine which intercarpal fusion procedures unload the
      lunate and whether they alter the force transmission through the entire wrist
      joint. Ten theoretical models of wrists were used to simulate three different
      operative procedures: capitate-hamate fusion, scapho-trapezial-trapezoidal
      fusion, and scaphocapitate fusion. A discrete element analysis technique was used
      to perform these investigations. The joint force and ligament tension of normal
      wrists and of simulated operative procedures were calculated according to the
      deformation of each spring element, simulating the articular cartilage and the
      carpal ligaments. Scaphocapitate and scapho-trapezial-trapezoidal fusions
      significantly decreased the joint force at the radiolunate joint and the
      lunocapitate joint compared with the intact wrist. In contrast, these fusions
      significantly increased this value at the radioscaphoid joint in comparison with
      the intact wrist. In the midcarpal joint, scaphocapitate fusion also increased
      the joint force at the scapho-trapezial-trapezoidal joints and at the triquetral
      hamate joint, whereas scapho-trapezial-trapezoidal fusion increased it at the
      scapho-capitate joint. Capitate-hamate fusion yielded no significant changes of
      the joint forces through the entire wrist joint. In the analysis of ligament
      tension, scaphocapitate and scapho-trapezial-trapezoidal fusions significantly
      decreased the tension only in the dorsal scapholunate ligament. These findings
      demonstrate that scaph-ocapitate and scapho-trapezial-trapezoidal fusions are
      effective in decompressing the lunate. By contrast, capitate-hamate fusion is
      ineffective in reducing lunate compression. Although scaphocapitate and scapho
      trapezial-trapezoidal fusions are recommended for the treatment of Kienbock's
      disease, clinicians should consider that the increase of force transmission
      through the radioscaphoid and the midcarpal joints may lead to early degenerative
      changes after these procedures have been performed.

PMID- 9621901
TI  - Posterior tilting of the tibial component decreases femoral rollback in posterior
      substituting knee replacement: a computer simulation study.
AB  - Posterior tilting of the tibial component is thought to increase the range of
      motion in posterior cruciate-retaining total knee replacement, but its effect on
      implant motion in posterior cruciate-substituting total knee replacement is
      unknown. This issue has become of interest recently because manufacturers have
      introduced instrumentation that produces a posteriorly tilted tibial cut for both
      implant types. The purpose of this study was to investigate how motion of
      posterior cruciate-substituting total knee replacement is affected when the
      tibial component is installed with posterior tilt. Sagittal plane implant motions
      were predicted from prosthesis geometry with use of a computer simulation in
      which the femoral condyles were assumed to sit in the bottoms of the tibial
      condylar wells when the knee was in extension. Rollback of the femoral component
      was produced by a cam-spine mechanism at higher angles of flexion. The
      simulations revealed that even small degrees of posterior tilt reduced rollback
      by limiting the interaction between the cam and spine. Tilting the component
      posteriorly by 5 degrees caused the cam to contact the spine at a knee flexion
      angle that was 18 degrees higher than with the untilted component. The results
      suggest that posterior tilting of the tibial component in posterior cruciate
      substituting knee replacement may not produce the same beneficial effects that
      have been reported for the tilting of tibial components in posterior cruciate
      retaining knee replacement.

PMID- 9621902
TI  - Postural balance measurements for children and adolescents.
AB  - Measurements of standing balance were determined for 92 children and adolescents,
      5-18 years old, while they stood on a force plate with eyes open or eyes closed.
      The measurements included center-of-pressure calculations for path length per
      second, average radial displacement, anterior-posterior and mediolateral
      amplitudes, area per second, mean frequency of sway, Brownian random motion
      measure of short-term diffusion coefficient, and long-term scaling exponent. All
      balance parameters improved from youngest to oldest subjects, and the parameters
      improved when measured with the subjects' eyes open compared with closed. The
      mean values for data from three trials varied by only 5% when compared with the
      mean values from 10 trials. Data from this study suggest that force-plate center
      of-pressure data can be used to determine differences in standing balance between
      children and adolescents of different ages and those with movement and balance
      abnormalities.

PMID- 9621903
TI  - Effects of a pressure target on laryngeal airway resistance in children.
AB  - The purpose of this study was to determine the effects of an intraoral air
      pressure target on estimation of laryngeal airway resistance (LAR) in normal
      children. Ten children produced the syllable /pi/ (a) with self-determined normal
      loudness, (b) with increased loudness, and (c) at a predetermined intraoral air
      pressure level of 6.5 to 7.5 cm of water. The target pressure level was selected
      because it was expected to result in estimated subglottal pressures that were
      lower than those associated with self-determined loudness levels. Results
      indicated significant differences in estimated subglottal pressure among the
      three conditions. As expected, estimated subglottal pressures were highest during
      loud speech and lowest during the pressure target task. LAR values associated
      with normal loudness were similar to values previously reported for children. The
      use of the pressure target resulted in LAR values that were reduced by 31% from
      normal loudness. These resistance values, however, were still greater than those
      reported for adult speakers at similar subglottal pressure levels. The results
      are explained relative to preferred loudness levels and vocal tract size
      differences in children and adults. It is suggested that use of a pressure target
      during estimation of LAR in children may provide additional data that more
      accurately reflect the aerodynamic integrity of the larynx. Implications for
      clinical assessment are discussed.

PMID- 9621904
TI  - Voice onset time in Spanish-English bilinguals: early versus late learners of
      English.
AB  - Thirty-two Hispanic speakers of English were evenly divided into two groups based
      on whether or not their initial learning of English began prior to, or after the
      age of 12 years. Each group had an even number of males (16) and females (16).
      The subjects were recorded producing a protocol of 18 basic speech syllables. The
      first three repetitions (54 tokens) were chosen for analysis. The 1728 tokens
      were digitized and measured for voice onset time (VOT). Findings support the
      hypothesis that the VOT values of Hispanics speaking English differ according to
      whether initial learning of English began prior to or after the age of 12 years.
      An analysis of variance (ANOVA) found significant main effects of group, place,
      voice, and gender. Significant interactions were group by voice, and voice by
      gender.

PMID- 9621905
TI  - Comparative study of the phonology of preschool children prenatally exposed to
      cocaine and multiple drugs and non-exposed children.
AB  - Cocaine and multiple drug abuse among young adults has spawned research interest
      in fetal exposure and the sequela of that exposure during the formative
      developmental years. Previous study of the language development of exposed
      children has not specifically addressed phonological acquisition. In the present
      study, the speech of 25 children prenatally exposed to cocaine and multiple drugs
      was analyzed and compared to that of 25 children who were not prenatally exposed
      to determine if differences were evident in their phonological patterns. The
      children ranged in age from 22 months to 51 months. The number and type of
      phonological processes produced, number of utterances needed to produce a 50-word
      sample, number of unintelligible words produced, and Home Observation for
      Measurement of the Environment (HOME) scores were recorded and analyzed. The use
      of cocaine and multiple drugs during pregnancy was associated with an increase in
      the use of phonological processes.

PMID- 9621906
TI  - Reliability of judgments of stuttering and disfluency in young children's speech.
AB  - This study examined interjudge agreement levels for two forms of judgments of
      overt speech characteristics in young children's speech: stuttering and
      disfluency types. Five experienced adult listeners made judgments of disfluencies
      and stuttering in samples of eight young children's spontaneous speech on
      separate occasions with the order of tasks counterbalanced across listeners.
      Results showed that the interjudge reliability for judgments based on a
      disfluency taxonomy was not significantly different from that based on
      stuttering. The high coefficients of reliability for both procedures indicated
      that subjects would be ranked consistently on the basis of either form of
      judgment. The importance of both forms of judgments to stuttering treatment and
      research is discussed.

PMID- 9621907
TI  - Conversational discourse analysis as a method for evaluating progress in aphasia:
      a case report.
AB  - The gains made by a woman with Broca's aphasia as documented by traditional
      measures were paralleled by changes in conversation, including increased verbal
      output and efficiency, and changes in conversation repair patterns. Her
      conversational partner decreased her verbal output, as predicted. The progress
      documented with conversational discourse analysis was not observable from other
      test measures. Clinical and theoretical implications are discussed.

PMID- 9621908
TI  - Dynamics of blood flow and oxygenation changes during brain activation: the
      balloon model.
AB  - A biomechanical model is presented for the dynamic changes in deoxyhemoglobin
      content during brain activation. The model incorporates the conflicting effects
      of dynamic changes in both blood oxygenation and blood volume. Calculations based
      on the model show pronounced transients in the deoxyhemoglobin content and the
      blood oxygenation level dependent (BOLD) signal measured with functional MRI,
      including initial dips and overshoots and a prolonged poststimulus undershoot of
      the BOLD signal. Furthermore, these transient effects can occur in the presence
      of tight coupling of cerebral blood flow and oxygen metabolism throughout the
      activation period. An initial test of the model against experimental measurements
      of flow and BOLD changes during a finger-tapping task showed good agreement.

PMID- 9621909
TI  - MRI of hyperpolarized 3He gas in human paranasal sinuses.
AB  - In this study, MRI of hyperpolarized 3He gas in human paranasal sinuses is
      presented. Helium images were obtained at 1.5 T, using a surface coil and a 2D,
      fast gradient-echo sequence with a nominal constant flip angle of 12 degrees.
      Coronal images of 20-mm thick slices were generated and compared with proton
      images of the corresponding sections. The images enable visualization of the
      paranasal sinuses and the nasal cavity, suggesting a potential use of this method
      not only in identifying the anatomical configuration of these pneumatic spaces,
      but also in assessing sinus ventilation.

PMID- 9621910
TI  - Pattern recognition analysis of 1H NMR spectra from perchloric acid extracts of
      human brain tumor biopsies.
AB  - Pattern recognition techniques (factor analysis and neural networks) were used to
      investigate and classify human brain tumors based on the 1H NMR spectra of
      chemically extracted biopsies (n = 118). After removing information from lactate
      (because of variable ischemia times), unsupervised learning suggested that the
      spectra separated naturally into two groups: meningiomas and other tumors.
      Principal component analysis reduced the dimensionality of the data. A back
      propagation neural network using the first 30 principal components gave 85%
      correct classification of meningiomas and nonmeningiomas. Simplification by
      vector rotation gave vectors that could be assigned to various metabolites,
      making it possible to use or to reject their information for neural network
      classification. Using scores calculated from the four rotated vectors due to
      creatine and glutamine gave the best classification into meningiomas and
      nonmeningiomas (89% correct). Classification of gliomas (n = 47) gave 62% correct
      within one grade. Only inositol showed a significant correlation with glioma
      grade.

PMID- 9621911
TI  - Temporal and regional changes during focal ischemia in rat brain studied by
      proton spectroscopic imaging and quantitative diffusion NMR imaging.
AB  - The early development of focal ischemia after permanent occlusion of the right
      middle cerebral artery (MCA) was studied in six rats using interleaved
      measurements by diffusion-weighted NMR imaging (DWI) of water and two variants of
      proton spectroscopic imaging (SI), multiecho SI (TE: 136, 272, 408 ms) and short
      TE SI (TE: 20 ms). Measurements on a 4.7-T NMR imaging system were performed
      between the control phase and approximately 6 h postocclusion. In the center of
      the ischemic lesion of all rats, the apparent diffusion coefficient (ADC)
      decreased rapidly to 84.4 +/- 4.2% (mean +/- SD) of the control values
      approximately 2 min postocclusion. Approximately 6 h postocclusion, the ADC was
      reduced to 67.1 +/- 5.9%. In contrast, large differences between the animals were
      observed for the temporal increase of lactate (Lac) in the ipsilateral
      hemisphere. The maximum Lac signal was reached in four rats after 0.5-1.5 h, and
      in two rats was not reached even after 6 h postocclusion. Six h postocclusion, SI
      spectra measured at a TE of 136 ms revealed a decrease in the CH3 signal of N
      acetylaspartate (NAA) to 67 +/- 13% of the control values. Differences were
      observed between the spatial regions of decreased NAA and increased Lac. In the
      lesions, a T2 relaxation time of Lac of 292 +/- 40 ms, considering a J-coupling
      constant of 6.9 Hz, was measured. Furthermore, a prolongation of the T2 of the
      CH3 signal of creatine/phosphocreatine (Cr/PCr) was observed in the lesion, from
      163 +/- 22 ms during control to 211 +/- 41 ms approximately 6 h postocclusion.
      The experiments proved that DWI and proton SI are valuable tools to provide
      complementary information on processes associated with brain infarcts.

PMID- 9621912
TI  - Volumetric spectroscopic imaging with spiral-based k-space trajectories.
AB  - Spiral-based k-space trajectories were applied in a spectroscopic imaging
      sequence with time-varying readout gradients to collect volumetric chemical shift
      information. In addition to spectroscopic imaging of low signal-to-noise ratio
      (SNR) brain metabolites, the spiral trajectories were used to rapidly collect
      reference signals from the high SNR water signal to automatically phase the
      spectra and to aid the reconstruction of metabolite maps. Spectral-spatial pulses
      were used for excitation and water suppression. The pulses were designed to
      achieve stable phase profiles in the presence of up to 20% variation in the
      radiofrequency field. A gridding algorithm was used to resample the data onto a
      rectilinear grid before fast Fourier transforms. This method was demonstrated by
      in vivo imaging of brain metabolites at 1.5 T with 10 slices of 18 x 18 pixels
      each. Nominal voxel size was 1.1 cc, spectral bandwidth was 400 Hz, scan time was
      18 min for the metabolite scan and 3 min for the reference scan.

PMID- 9621913
TI  - Versatile frequency domain fitting using time domain models and prior knowledge.
AB  - An iterative nonlinear least-squares fitting algorithm in the frequency domain
      using time domain models for quantification of complex frequency domain MR
      spectra is presented. The algorithm allows incorporation of prior knowledge and
      has both the advantage of time-domain fitting with respect to handling the
      problem of missing data points and truncated data sets and of frequency-domain
      fitting with respect to multiple frequency-selective fitting. The described
      algorithm can handle, in addition to Lorentzian and Gaussian lineshapes, Voigt
      and nonanalytic lineshapes. The program allows the user the design of his own
      fitting strategy to optimize the probability of reaching the global least-squares
      minimum. The application of the fitting program is illustrated with examples from
      in vivo 1H-, 31P-, and 13C-MR spectroscopy.

PMID- 9621914
TI  - Temporal characteristics of oxygenation-sensitive MRI responses to visual
      activation in humans.
AB  - Series of single-shot blipped echo-planar images with spin-density weighting and
      T2* sensitivity (2.0 T, TR = 400 ms, TE = 54 ms, flip angle = 30 degrees) were
      used to study the temporal response profiles to repetitive visual activation (5
      Hz, reversing black and white checkerboard versus darkness) for protocols
      comprising multiple cycles of a 1.6-s stimulus in conjunction with a 8.4-s or 90
      s recovery phase and a 10-s stimulus with a 20-s or 90-s recovery phase. Analysis
      of the real-time data from all activated pixels resulted in a strong positive MRI
      response (mean values 3-6%) as well as a marked poststimulus undershoot (mean
      values 1-2%, duration 60-90 s) for all paradigms. Repetitive protocols with
      insufficient recovery periods of 8.4 s or 20 s gave rise to a wraparound effect
      when analyzing time-locked averages from multiple activation cycles. This problem
      may lead to an early signal decrease that originates from the ongoing undershoot
      of preceding activations folded back into the initial latency phase of a
      subsequent activation. When ensuring complete decoupling of responses to
      successive stimuli by using a 90-s recovery period, the wraparound effect
      vanished and an initial dip was observed in one of seven subjects for a 10-s/90-s
      protocol.

PMID- 9621915
TI  - Temporal and anatomical variations of brain water apparent diffusion coefficient
      in perinatal cerebral hypoxic-ischemic injury: relationships to cerebral energy
      metabolism.
AB  - Cerebral apparent diffusion coefficients (ADCs) were determined in nine newborn
      piglets before and for 48 h after transient hypoxia-ischemia. Phosphorus MRS
      revealed severely reduced cerebral energy metabolism during the insult and an
      apparently complete recovery 2 h after resuscitation commenced. At this time,
      mean ADC over the imaging slice (ADCglobal) was 0.88 (0.04) x 10(-9) m2 x s(-1)
      (mean (SD)), which was close to the baseline value of 0.92 (0.4) x 10(-9) m2 x s(
      1). In seven of the animals, a "secondary" failure of energy metabolism then
      evolved, accompanied by a decline in ADCglobal to 0.64 (0.17) x 10(-9) m2 x s(-1)
      at 46 h postresuscitation (P < 0.001 versus baseline). For these seven animals,
      ADCglobal correlated linearly with the concentration ratio [phosphocreatine
      (PCr)]/[inorganic phosphate (Pi)] (0.94 < r < 0.99; P < 0.001). A nonlinear
      relationship was demonstrated between ADCglobal and the concentration ratio
      [nucleotide triphosphate (NTP)]/[Pi + PCr + 3 NTP]. The ADC reduction commenced
      in the parasagittal cortex before spreading in a characteristic pattern
      throughout the brain. ADC seems to be closely related to cerebral energy status
      and shows considerable potential for the assessment of hypoxic-ischemic injury in
      the newborn brain.

PMID- 9621916
TI  - A simplified method to measure the diffusion tensor from seven MR images.
AB  - Analytical expressions of the diffusion tensor of water, D, and of scalar
      invariants derived from it, are given in terms of the intensities of seven
      diffusion-weighted images (DWIs). These formulas simplify the post-processing
      steps required in diffusion tensor imaging, including estimating D in each voxel
      (from the set of b-matrices and their corresponding DWIs), and then computing its
      eigenvalues, eigenvectors, and scalar invariants. In a study conducted using
      artifact-free DWIs with high diffusion weighting (bmax approximately 900 s/mm2,
      maps of Trace(D) and the Relative and Lattice Anisotropy indices calculated
      analytically and by multivariate linear regression showed excellent agreement in
      brain parenchyma of a healthy living cat. However, the quality of the
      analytically computed maps degraded markedly as diffusion weighting was reduced.
      Although diffusion tensor MRI with seven DWIs may be useful for clinical
      applications where rapid scanning and data processing are required, it does not
      provide estimates of the uncertainty of the measured imaging parameters,
      rendering it susceptible to noise and systematic artifacts. Therefore, care
      should be taken when using this technique in radiological applications.

PMID- 9621917
TI  - Automatic segmentation of gadolinium-enhanced multiple sclerosis lesions.
AB  - Automatic detection and quantitation of contrast-enhanced lesions on MRI is
      expected to be useful in characterizing the disease state in multiple sclerosis
      (MS). The enhancing structures such as cerebral vasculature and regions with no
      blood-brain barrier complicate automated analysis of lesion enhancement. A pulse
      sequence that incorporates both stationary and marching saturation bands and
      gradient dephasing is described for suppressing the enhancements within the
      cerebral vasculature. A postprocessing technique based on automatic image
      segmentation is implemented for eliminating enhancing structures such as choroid
      plexus. All MS lesions larger than 5 mm3 have been successfully identified. The
      automated analysis produced no false-positives or false-negative lesions above
      this volume in 13 patients with MS who were evaluated using the acquisition and
      evaluation techniques described.

PMID- 9621918
TI  - Relaxation anisotropy in cartilage by NMR microscopy (muMRI) at 14-microm
      resolution.
AB  - To study the structural anisotropy and the magic-angle effect in articular
      cartilage, T1 and T2 images were constructed at a series of orientations of
      cartilage specimens in the magnetic field by using NMR microscopy (muMRI). An
      isotropic T1 and a strong anisotropic T2 were observed across the cartilage
      tissue thickness. Three distinct regions in the microscopic MR images
      corresponded approximately to the superficial, transitional, and radial
      histological zones in the cartilage. The percentage decrease of T2 follows the
      pattern of the curve of (3cos2theta - 1)2 at the radial zone, where the collagen
      fibrils are perpendicular to the articular surface. In contrast, little
      orientational dependence of T2 was observed at the transitional zone, where the
      collagen fibrils are more randomly oriented. The result suggests that the
      interactions between water molecules and proteoglycans have a directional nature,
      which is somehow influenced by collagen fibril orientation. Hence, T2 anisotropy
      could serve as a sensitive and noninvasive marker for molecular-level
      orientations in articular cartilage.

PMID- 9621919
TI  - A quantitative method for fast diffusion imaging using magnetization-prepared
      TurboFLASH.
AB  - For the in vivo measurement of the apparent diffusion coefficient (ADC), it is
      desirable for the total imaging time to be as short as possible. One technique is
      based on a TurboFLASH acquisition in which the diffusion gradients are inserted
      into a driven equilibrium Fourier transform (DEFT) combination of hard pulses.
      However, this sequence has the disadvantage that eddy current-induced
      inhomogeneities lead to incomplete refocusing of the magnetization during the
      diffusion preparation and to incorrect ADC values. A modification to the sequence
      is suggested that eliminates this error by phase-cycling the second 90 degrees
      pulse of the preparation. This study also investigates the effect of a reduced
      delay time between acquisitions on the accuracy of the measurement. The quality
      of the TurboFLASH sequence is demonstrated by experimental validation on an agar
      phantom and in vivo on the rat brain using a high-field (8.5 T) system. Reduction
      of the interexperiment delay time is shown to be achievable to a certain degree
      without compromising the measurement accuracy.

PMID- 9621920
TI  - Volumetric analysis of white matter, gray matter, and CSF using fractional volume
      analysis.
AB  - Quantitative cerebral tissue volumes may be useful for an objective assessment of
      pathological changes in brain. Accurate determination of tissue volumes is
      complicated, however, by the partial volume averaging (PVA) effect. We have,
      therefore, developed a new pulse sequence that minimizes the PVA through the use
      of inversion-recovery (IR) and double inversion-recovery (DIR) techniques. This
      pulse sequence simultaneously acquires four different sets of images to provide
      the necessary information for volumetric analysis and reduces potential spatial
      misregistration of images due to patient motion. The image sets acquired from the
      proposed pulse sequence are 1) gray matter visible, 2) white matter visible, 3)
      FLAIR, and 4) fast spin-echo proton-density weighted images. An algorithm has
      been implemented to correct for differential T1-weighting and for tissue
      quantitation.

PMID- 9621921
TI  - GRASE imaging at 3 Tesla with template interactive phase-encoding.
AB  - A new method for ordering the phase-encoding gradient is proposed, and an
      application for short effective TE gradient- and spin-echo (GRASE) imaging is
      demonstrated. The proposed method calculates the phase-encoding order from the
      signal decay of a template scan (hence "template interactive phase-encoding" or
      TIPE). Computer simulations are used to compare the point spread functions of
      different phase-encoding orders giving short effective echo times (kb centric
      GRASE, centric GRASE, centric TIPE). The conventional centric phase-encoding
      order is also considered for GRASE. The conventional centric method is sensitive
      to both amplitude and phase modulation of the signal in k-space. The centric TIPE
      method gives the least amplitude modulation artifacts but is vulnerable to phase
      artifacts. The TIPE experiment was implemented on a 3 Tesla system. To the best
      of our knowledge, we present the first in vivo GRASE images at this field
      strength.

PMID- 9621922
TI  - Cardiac MRI of the normal and hypertrophied mouse heart.
AB  - With the development of recent transgenic techniques, studies involving mice
      offer opportunities to increase understanding of cardiac disease. This provides
      motivation for the current study to perform noninvasive evaluation of the normal
      and hypertrophied mouse heart with MRI. By acquiring ECG and respiratory signals,
      the MR image acquisition was gated to both the cardiac and respiratory cycles.
      Combining a spin-warp imaging sequence with an RF surface coil resulted in short
      axis images that allowed quantification of in vivo cardiac mass. Excellent
      agreement between MRI-determined (y) and postmortem heart weight (x) was
      obtained: y = 0.991x + 1.43 (r = 0.996). Isoproterenol, at 282 micromol/kg body
      weight (BW) and 573 micromol/kg BW, induced a dose-dependent increase in the
      ratio of heart weight to BW of 16.8 +/- 1.09% and 24.1 +/- 1.71%, respectively,
      which was accurately measured by MRI. These results demonstrate the ability of
      MRI to noninvasively monitor cardiac anatomy in the mouse.

PMID- 9621923
TI  - In vivo measurement of T*2 and field inhomogeneity maps in the human heart at 1.5
      T.
AB  - Cardiac echo-planar imaging suffers invariably from regions of severe distortion
      and T*2 decay in the myocardium. The purpose of this work was to perform local
      measurements of T*2 and field inhomogeneities in the myocardium and to identify
      the sources of focal signal loss and distortion. Field inhomogeneity maps and T*2
      were measured in five normal volunteers in short-axis slices spanning from base
      to apex. It was found that T*2 ranged from 26 ms (SD = 7 ms, n = 5) to 41 ms (SD
      = 11 ms, n = 5) over most of the heart, and peak-to-peak field inhomogeneity
      differences were 71 Hz (SD = 14 Hz, n = 5). In all hearts, regions of severe
      signal loss were consistently adjacent to the posterior vein of the left
      ventricle; T*2 in these regions was 12 ms (SD = 2 ms, n = 5), and the difference
      in resonance frequency with the surrounding myocardium was 70-100 Hz. These
      effects may be caused by increased magnetic susceptibility from deoxygenated
      blood in these veins.

PMID- 9621924
TI  - A novel k-space trajectory measurement technique.
AB  - A new k-space trajectory measurement technique is proposed and demonstrated. This
      technique measures the k-space trajectory, in seconds, using only a few readout
      lines, using phase values of acquired MR signals. As a result of the technique's
      efficiency, k-space trajectory measurement using patient data becomes possible.
      The utility of this techniques is demonstrated in phantom and human studies at
      4.1 T.

PMID- 9621925
TI  - Lack of effect of oral choline supplement on the concentrations of choline
      metabolites in human brain.
AB  - Recent reports suggest that oral choline supplement may alter the cerebral
      choline/creatine (Cho/Cr) ratio and might be used to treat neurodegenerative
      disorders of cholinergic transmission. Using both 1H and 31P MRS, we reexamined
      the Cho/Cr ratio and quantified cerebral choline and its major constituents:
      phosphoethanolamine (PE), phosphorylcholine (PC), glycerophosphorylethanolamine
      (GPE), and glycerophosphorylcholine (GPC). In the four brain locations examined,
      no significant increases in Cho/Cr, [Cho], or in its major constituents were
      found in response to an oral challenge of 50 mg/kg of choline bitartrate. Oral
      choline did not significantly affect human cerebral metabolism in the short term.

PMID- 9621926
TI  - Measurement of chemical shifts and coupling constants for glutamate and
      glutamine.
AB  - Proton chemical shifts and coupling constants were obtained for glutamate and
      glutamine in water (D2O) at pH = 6.6. Initial chemical shift and coupling
      constant values obtained from experimental spectra were refined using a spectral
      simulation and optimization program to get a complete set of values that could
      not otherwise be measured directly from the experimental spectra due to strong
      spin-spin couplings. These values are essential for automated spectral fitting
      procedures that require a priori information.

PMID- 9621927
TI  - Three-dimensional MRI of coronary arteries using an intravascular contrast agent.
AB  - To assess the effectiveness of an intravascular contrast agent, MS-325, for
      enhancing the vascular signal in coronary MR angiograms, six minipigs were
      studied using a three-dimensional, gradient-echo sequence with retrospective
      respiratory gating. To suppress the myocardial signal, preparatory RF pulses were
      applied before data acquisition. With the administration of MS-325, the blood
      signal-to-noise ratio increased by 97-276%, depending on the region of interest
      in which the blood signal was measured and the precontrast imaging sequence
      structures. The blood/myocardium contrast-to-noise ratio also significantly
      increased. High-resolution images (0.58 x 0.58 x 1 mm3) obtained from postmortem
      pig hearts demonstrated the potential delineation of coronary arteries with MS
      325. In conclusion, this study supports further evaluation of the utility of MS
      325 in improving coronary MR angiography in humans.

PMID- 9621928
TI  - Virtual frequency encoding: achieving symmetry in k-space.
AB  - Chemical shift artifacts and other off-resonance spatial shifts in 2DFT MRI arise
      from the linear time dependence in the k-space data in the readout direction.
      Introduction of a view-dependent time shift of the readout window adds a time
      dependence to the phase-encoding direction and results in a virtual frequency
      encoding direction that is a linear combination of the phase-encode and readout
      axes. By this method, the readout and phase-encode directions can be made
      identical in their sensitivity to off-resonance effects and can be arbitrarily
      swapped with no change in chemical shift or inhomogeneity effects, improving
      previously reported methods that swap these axes for signal averaging or
      reduction of motion artifacts.

PMID- 9621929
TI  - Relationships among ewe milk production and ewe and lamb forage intake in Suffolk
      and Targhee ewes nursing single or twin lambs.
AB  - Suffolk and Targhee ewes (30 each) with single or twin lambs were used in four
      periods beginning in late gestation and continuing through weaning to evaluate
      breed differences in milk production, lamb BW, and DMI by ewes and lambs. In
      Periods 1 (late gestation) and 2 (early lactation), ewes (Period 1) and ewes with
      lambs (Period 2) were individually penned, fed .45 kg of barley x ewe(-1) x d(-1)
      and allowed ad libitum access to chopped alfalfa. Ewes and lambs grazed native
      range in Periods 3 and 4. Grazed forage DMI was estimated using chromic oxide.
      Estimates of milk production were obtained by handmilking. Average lamb age was
      4, 45, and 73 d at the beginning of Periods 2, 3, and 4, respectively. Milk
      production tended (P = .20) to be greater for Suffolk than for Targhee ewes.
      Targhee ewes produced 85% more (P = .001) wool than Suffolk ewes. From 33 d
      prepartum to 89 d postpartum, Suffolk ewes consistently weighed more (P = .001)
      than Targhee ewes. Suffolk ewe BW loss (-.15 kg/d) was greater (P = .01) than
      Targhee ewe BW loss (-.02 kg/d) from 33 d prepartum to 6 d postpartum. From 6 to
      89 d postpartum BW gain did not differ (P = .69; .05 kg/d) between breeds. From
      birth to 89 d postpartum, Suffolk lambs consistently weighed more than Targhee
      lambs (P = .003). From birth to 89 d postpartum, ADG was greater for Suffolk than
      for Targhee lambs (P = .006). Targhee ewes consumed 25% more (P = .01) feed over
      the course of the study than did Suffolk ewes. Grazed forage DMI by Targhee lambs
      was 26% greater (P = .01) than DMI by Suffolk lambs. When meat production is the
      primary income from sheep, one potential advantage of Suffolks compared with
      Targhees is more rapid gain with less feed intake.

PMID- 9621930
TI  - Growth of Holstein dairy heifers in the United States.
AB  - Data were collected on the heart girth (n = 8,565; a measure of body weight) and
      height at withers (n = 8,568) of Holstein dairy heifers from 659 dairy farms as
      part of the National Dairy Heifer Evaluation Project during 1991 and 1992. Means
      and standard deviations for weight and height were determined for ages .5 to 23.5
      mo. Third-order polynomial regression equations were derived to study the
      relationship of weight and height to age. Stepwise mixed-model regression, using
      REML estimation, was used to identify factors associated with Holstein heifer
      growth and to build a multivariate model describing Holstein heifer growth across
      the United States. Holstein heifers on the sample of dairy farms in this study
      were heavier and taller at the withers than standards published 30 to 50 yr ago.
      Increased rolling herd average milk production was associated with a greater rate
      of growth in Holstein heifers. Holstein heifers in the West and Midwest were
      larger at a given age than those in the Northeast and Southeast.

PMID- 9621931
TI  - Measurement of medullation in wool and mohair using an Optical Fibre Diameter
      Analyser.
AB  - We conducted three experiments to evaluate the Optical Fibre Diameter Analyser
      (OFDA) for estimating medullation (med [M], kemp [K], and total [T] medullated
      fiber content) in mohair and wool produced by Angora goats and sheep,
      respectively. Medullation can be a beneficial characteristic in certain types of
      wool, but it is highly undesirable in mohair and apparel wools. Current
      techniques for evaluating medullation in animal fibers are laborious, slow, and
      expensive. The OFDA had been modified by the manufacturer to measure fiber
      opacity distribution, a characteristic known to be indicative of medullation in
      white fibers, and was capable of providing such measurements in a very short
      time. Measurements made on magnified fiber images produced with a projection
      microscope (PM) were used as a reference for M, K, and T in fiber samples. An
      initial experiment with 124 mohair samples (T = .10 to 9.10%) seemed to indicate
      that OFDA estimates of M, K, and T were only poorly correlated with corresponding
      PM values (r2 = .5409, .1401, and .5576, respectively). However, a second
      experiment using wool and mohair samples containing a wider range of medullation
      (T = .58 to 26.54%) revealed that OFDA estimates of M, K, and T for wool were
      highly correlated with PM measurements (r2 = .9853, .9307, and .9728,
      respectively). Evidence was also obtained indicating that the low r2 values
      associated with mohair relationships were likely due to a combination of factors:
      1) high variation among the standard PM measurements and 2) the relatively low M,
      K, and T contents of the mohair samples compared with wool. In a third
      experiment, greater accuracy was obtained in the PM measurements by evaluating
      many more individual fibers per sample (10,000). In this case, OFDA estimates of
      M, K, and T for mohair were highly correlated with corresponding PM measurements
      (r2 = .8601, .9939, and .9696, respectively). However, the two sets of linear
      regression equations obtained for wool and mohair were somewhat different,
      indicating that separate calculations should be used to estimate PM measurements
      from OFDA data. In conclusion, it was demonstrated that the OFDA instrument is
      capable of providing relatively fast, accurate, and potentially less expensive
      estimates of medullated fiber characteristics in mohair and wool.

PMID- 9621932
TI  - Development of a progestin-based estrus synchronization program: I. Reproductive
      response of cows fed melengestrol acetate for 20 days with an injection of
      progesterone.
AB  - We designed two experiments to determine the efficacy of an estrus control system
      in cows that combined long-term progestin exposure (20 d) with an acute increase
      in progesterone concentration. In Exp. 1, cows (n = 30) were fed either
      melengestrol acetate (MGA; .5 mg x cow(-1) x d(-1)) or ground ear corn (MGA
      carrier) for 20 d. On d -15 (last day of MGA feeding = d 0), cows were
      administered 25 mg of PGF2alpha to regress the corpus luteum (CL) and establish
      an environment conducive to the development of persistent follicles. To
      synchronously regress persistent follicles, cows fed MGA (n = 15) were injected
      with 200 mg of progesterone on d -2 (MGA-P), and the cows fed the MGA carrier
      were not treated (CONT; n = 15). Cows in the CONT group were artificially
      inseminated 12 h after detection of spontaneous estrus from d -20 to d 8. Estrus
      was observed, and all cows in the MGA-P group were artificially inseminated
      during the period of estrus synchronization (SYNC; d 1 to 8). No difference in
      conception rate was observed between treatments. In Exp. 2, postpartum cows (n =
      113) received either the MGA-P (n = 56) or CONT (n = 57) treatment. More (P <
      .05) cows were observed in estrus during SYNC in the MGA-P (50%) than in the CONT
      (28%) group. Of the cows in the MGA-P group that were not observed in estrus
      during SYNC, 50% were in estrus for the first time 23 to 29 d after MGA
      withdrawal (SYNC2), suggesting that these cows ovulated without observable estrus
      during SYNC. Estrus was observed for the first time during SYNC2 in more (P <
      .05) cows in the MGA-P (25%) than in the CONT (7%) group. Conception rate at the
      synchronized estrus, pregnancy rate, and interval to first service and pregnancy
      were similar between treatments. We conclude that administration of MGA-P results
      in the synchronization and(or) induction of a fertile estrus in cows.

PMID- 9621933
TI  - Development of a progestin-based estrus synchronization program: II. Reproductive
      response of cows fed melengestrol acetate for 14 days with injections of
      progesterone and prostaglandin F2alpha.
AB  - We tested the efficacy of an estrus control system designed to provide optimal
      control of follicular development. In Exp. 1, postpartum cows (n = 133) and
      yearling heifers (n = 57) were fed either .5 mg x female(-1) x d(-1) of
      melengestrol acetate (MGA) or the carrier for MGA from d -13 to d 0 (d 0 = last
      day of MGA feeding). All females received 25 mg of PGF2alpha (i.m.) on d -13 and
      0. On d -6, cows and heifers fed MGA were administered an i.m. injection of
      progesterone (200 mg; MGA/P4), and those fed the corn carrier (2XPGF2alpha)
      received no progesterone. Beginning on d 1, females were bred by AI from d 1 to
      at least d 5. During the estrus synchronization period (d 1 to d 5), more (P <
      .05) postpartum cows were observed in estrus (70.1 vs 42.4%), the timing of
      estrus was more (P < .05) precise, conception rate was similar, and pregnancy
      rate was higher (P < .05) in the MGA/P4 than in the 2XPGF2alpha treatment. More
      (P < .05) cows that were anestrous at the beginning of the breeding season were
      in estrus during the synchronization period in the MGA/P4 (55.8%) than in the
      2XPGF2alpha (28.6%) treatment. In heifers, estrus was synchronized in over 90% of
      females, and neither conception nor pregnancy rate during the synchronization
      period differed between treatments. In Exp. 2, postpartum cows (n = 122) and
      heifers (n = 84) received treatments (MGA/P4 or 2XPGF2alpha) as described for
      Exp. 1 with one exception. In the MGA/ P4 treatment, progesterone was
      administered on d -7 rather than d -6. Females were bred by AI from d 1 to 5. The
      estrus response and conception rate during the synchronization period did not
      differ between treatments for either cows or heifers. We conclude that the
      progestin-based estrous synchronization system used in this study effectively
      synchronized an estrus of normal fertility in cyclic cows and induced a majority
      of anestrous cows to reinitiate estrous cycles.

PMID- 9621934
TI  - An evaluation of ruminally degradable intake protein and metabolizable amino acid
      requirements of feedlot calves.
AB  - Ruminally degradable intake protein (DIP) and metabolizable indispensable amino
      acid (MIAA) requirements of feedlot steers were evaluated. Dietary treatments
      consisted of isocaloric 80% concentrate steam-flaked corn-based diets containing
      either .8% urea, 1.5% fish meal (FM), 3.0% FM, 4.5% FM, or 4.5% soybean meal
      (SBM). Treatment effects on characteristics of ruminal and total tract digestion
      were evaluated using four Holstein steers (249 kg) with cannulas in the rumen and
      proximal duodenum. Ruminal digestibility of OM (RDOM; P < .05) and feed N (P <
      .01) and microbial N flow (MNF; P < .01) to the small intestine were greater with
      urea as the supplemental N source. The level of DIP was closely associated (R2 =
      .89) with MNF. Postruminal digestibility of OM was greater (P < .05) for FM than
      for urea-supplemented diets, compensating for lower RDOM. There were no treatment
      effects (P > .10) on DOM. As the level of FM was increased, MIAA increased
      linearly (P < .01). Intestinal MIAA were similar (P > .10) for urea- and SBM
      supplemented diets. Treatment effects on 56-d growth performance were evaluated
      using 100 medium-framed crossbred steers (231 kg). Daily weight gain (linear
      effect; P < .01), DM intake (linear effect; P < .10), feed efficiency (linear
      effect; P < .05), and diet NE (linear effect; P < .05) increased with level of FM
      supplementation. Daily weight gain (P < .10) and DM intake (P < .05) were greater
      for urea- than for SBM-supplemented diets. Using bovine tissue as the reference
      protein, the biological value (based on chemical score) of the intestinal chyme
      protein averaged 73%; methionine was first-limiting. There was a close
      association (R2 = .99) between methionine supply to the small intestine and
      observed/expected dietary NE. The metabolizable methionine requirement (MMETR,
      g/d) of medium-framed feedlot steers can be reliably predicted from measures of
      BW and ADG (MMETR = 1.565 + .0234ADG[268 - (29.4 x .0557BW(.75)ADG(1.097))/ADG] +
      .0896BW(.75)). There was a very close association (R2 = .89) between DIP and MNF
      (MNF = 13.7DIP - .66DIP(2) + 25.9). At maximal observed synthesis, DIP accounted
      for 76% of the MNF. A minimum of 100 g DIP/kg of total tract digestible OM was
      required to maximize RDOM and MNF.

PMID- 9621935
TI  - Covariance components and prediction for additive and nonadditive preweaning
      growth genetic effects in an Angus-Brahman multibreed herd.
AB  - Estimates of covariances and sire expected progeny differences of additive and
      nonadditive direct and maternal genetic effects for birth and weaning weights
      were obtained using records from 1,581 straightbred and crossbred calves from the
      Angus-Brahman multibreed herd at the University of Florida. Covariances were
      estimated by Restricted Maximum Likelihood, using a Generalized Expectation
      Maximization algorithm applied to multibreed populations. Estimates of
      heritabilities and additive genetic correlations for straightbred and crossbred
      groups were within the ranges of values found in the literature for these traits.
      Maximum values of interactibilities (ratios of nonadditive genetic variances to
      phenotypic variances) and nonadditive correlations were somewhat smaller than
      heritabilities and additive genetic correlations. Sire additive and total direct
      and maternal genetic predictions for birth and weaning weight tended to increase
      with the fraction of Brahman alleles, whereas nonadditive direct and maternal
      genetic predictions were similar for sires of all Angus and Brahman fractions.
      These results showed that it is feasible to evaluate sires for additive and
      nonadditive genetic effects in a structured multibreed population. Data from
      purebred breeders and commercial producers will be needed to accomplish the same
      goal at a national level.

PMID- 9621936
TI  - Effects of inbreeding and heterozygosity on preweaning traits in a closed
      population of Herefords under selection.
AB  - Records of five inbred lines at the Livestock and Range Research Laboratory were
      used to evaluate effects of inbreeding and heterozygosity on preweaning traits.
      Members of each line were descendants of a single founder Hereford bull. A total
      of 8,065 records of birth weight and 7,380 records of preweaning daily gain and
      weaning weight were analyzed by derivative-free REML using a model that included
      fixed effects of sex, combination of year and month of birth and parity of dam,
      with covariates for direct and maternal genetic fractions of inheritance from the
      genetic groups, inbreeding, and heterozygosity fractions. Heterozygosity
      fractions were computed for crosses between lines. The random model effects were
      direct and maternal genetic and uncorrelated maternal permanent environmental and
      temporary environmental. Direct inbreeding and heterozygosity fractions averaged
      .098 and .343, and maternal inbreeding and heterozygosity fractions averaged .075
      and .294. Regression coefficients of traits on direct and maternal inbreeding
      fractions were -5.8 +/- 1.1 and -4.7 +/- 1.3 for birth weight, -.189 +/- .031 and
      -.252 +/- .039 for preweaning daily gain, and -44.5 +/- 6.6 and -56.1 +/- 8.4 kg
      for weaning weight. Estimates for direct heritability, maternal heritability, and
      direct-maternal genetic correlations were .37, .12, and -.01 for birth weight;
      .16, .25, and -.27 for daily gain; and .17, .26, and -.21 for weaning weight.
      Results suggest that heterosis represents recovery of accumulated inbreeding
      depression. Results also indicate that selection can overcome inbreeding
      depression and antagonism exists between direct and maternal genetic effects for
      preweaning traits.

PMID- 9621937
TI  - Responses to various selection protocols for lamb production in Rambouillet,
      Targhee, Columbia, and Polypay sheep.
AB  - To investigate the effectiveness of four selection protocols for improving
      reproduction in sheep, we evaluated nine selection lines and two random-bred
      control lines for lamb and wool production. Results were based on 25,026 dam and
      30,628 lamb records from Rambouillet (R), Targhee (T), Columbia (C), and Polypay
      (P) sheep collected from 1976 through 1988. Phenotypic trends over years were
      positive (P < .01) for most reproductive traits, body weight, wool grade (coarser
      grades), and lamb weaning weight in nearly all selected lines. Small positive
      trends for both random-bred control lines indicated there were improvements in
      management and(or) environment during the period. Small but significant
      phenotypic declines in fleece weights occurred in most lines, including controls.
      Substantial genetic gains (P < .01) in litter weight weaned (120 d), net
      reproductive rate (lambs weaned divided by ewes mated), prolificacy, body weight,
      and weaning weight were made in nearly all selected lines. There were also small
      but significant improvements in milk score in most lines. There were significant
      genetic declines and improvements in fleece weights; however, the average genetic
      change in fleece weight for lines selected for litter weight weaned was
      negligible. Genetic improvement in litter weight weaned was attributed
      approximately 37% to prolificacy, 27% to percentage of lambs weaned, 17% to lamb
      weaning weight, 12% to fertility, and 7% to ewe viability from breeding to
      lambing. On average, selection based on independent culling levels (litter weight
      weaned plus yearling body weight), yearling body weight, or early puberty was
      only 85, 67, or 59%, respectively, as effective as that based solely on litter
      weight weaned for improving litter weight weaned. The net value of the average
      (over all breeds) annual increase in production per ewe resulting from selection
      for litter weight weaned accumulated over 12 yr to an estimated $11.40 and $21.51
      annually for genetic and phenotypic increases, respectively.

PMID- 9621938
TI  - Effects of floor area allowance and group size on the productivity of
      growing/finishing pigs.
AB  - Six group sizes and three levels of floor area allowance were studied in a 6 x 3
      factorial arrangement. Group sizes were 3, 5, 6, 7, 10, and 15 pigs per pen.
      Floor area allowances were .030, .039, and .048 m2 x BW(.667). All pens were
      square and equipped with a single space feeder and nipple drinker near one
      corner. Pigs were fed a pelleted diet. Initial weights averaged 25.0 kg, and pigs
      remained on test for 12 wk. Pigs were weighed, feed intake was determined, and
      size of pens was increased at 2-wk intervals. Pen size was adjusted to provide
      the space required for the midpoint of each weigh period. Two replicates of the
      study were conducted. The ADG was reduced with increasing group size (899, 851,
      868, 872, 857, and 821 g, SEM = 16.4, for 3, 5, 6, 7, 10, and 15 pigs,
      respectively; P < .05), but the CV for gain (mean = .185) did not differ among
      group sizes. The ADFI also decreased with increasing group size (2.49, 2.34,
      2.32, 2.28, 2.28, and 2.21 kg, SEM = .036, for 3, 5, 6, 7, 10, and 15 pigs,
      respectively; P < .05). Feed efficiency (gain/intake) was highest for group sizes
      of 7 and 10 pigs (.381) and lowest for pens of three and five pigs (.363; P <
      .05). The ADG and ADFI (832 g and 2.25 kg, respectively) for the most crowded
      space allowance were reduced compared to more spacious allowances (ADG and ADFI
      of 875 and 877 g, and 2.35 and 2.36 kg, for .039 and .048 m2 x BW(.667),
      respectively; P < .05). Efficiency did not differ among space allowances. These
      results confirm previous studies reporting a negative effect of increasing group
      size on productivity, but our study suggests that gain and intake reach a plateau
      at less space allowance than previously reported.

PMID- 9621939
TI  - Biochemical identification and biological origin of key odor components in
      livestock waste.
AB  - Animal production results in conversion of feeds into valuable products such as
      meat, milk, eggs, and wool as well as into unavoidable and less desirable waste
      products. Intensification of animal numbers and increasing urbanization has
      resulted in considerable attention to odorous gases produced from animal wastes.
      It is clear that animal manure was, and still is, a valuable resource. However,
      it may be a major obstacle to future development of the animal industry if its
      impact on the environment is not properly controlled. Poor odor prevention and
      control from animal wastes is related to a lack of knowledge of the fundamental
      nature of odor and its production by farm animals. Odor, like noise, is a
      nuisance or disturbance and there is no universally accepted definition of an
      objectionable odor. Thus, regulation and control of odors in the environment is
      difficult because of the technical difficulties of defining odor limits and their
      measurement and evaluation. A variety of direct (sensory) and indirect
      (analytical instruments) methods for measuring odor intensity and determination
      of individual or key odor components are discussed. The biological origins of the
      four principal classes of odor compounds, namely branched- and straight-chain
      VFA, ammonia and volatile amines, indoles and phenols, and the volatile sulfur
      containing compounds, are reviewed. Because more than 50% of N from animals is
      excreted as urea, one strategy to conserve N in waste is to inhibit the urease
      enzyme that converts urea to ammonia. Laboratory studies to evaluate di- and
      triamide compounds to control urea hydrolysis in slurries of cattle and swine
      wastes are presented. Finally, a brief overview of various intervention
      strategies is provided. Multiple combinations of nutritional management, housing
      systems, treatment options as well as storage and disposal of animal wastes will
      be required to reduce environmental pollution and provide for long-term
      sustainable growth.

PMID- 9621940
TI  - Livestock odors: implications for human health and well-being.
AB  - The purpose of this paper is to examine the potential effects of livestock odors
      on the health and well-being of neighbors. Complaints of odor nuisance have
      become more frequent in communities surrounding areas with high concentrations of
      livestock. This increase in complaints from livestock odors parallels increased
      complaints of odor in general, including ammonia, diesel exhaust, beauty
      products, cleaners, and paints. Persons who report symptoms from odors generally
      find problems with many different types of odorous compounds. A review of recent
      studies suggests that the main complaints of health symptoms from odors are eye,
      nose, and throat irritation, headache, and drowsiness. Sensory irritation
      (pungency) can be produced by a broad range of odorous volatile organic compounds
      from trees, flowers, foods (pepper and ginger) as well as emissions from
      livestock operations. Odors can also potentially affect mood and memory. Further
      research is required to assess fully the health impact of odors in order to
      establish recommendations for air quality guidelines based on scientific data.

PMID- 9621941
TI  - Effect of protein and protein-free energy intake on plasma concentrations of
      insulin-like growth factor I and thyroid hormones in preruminant calves.
AB  - We conducted two experiments with preruminant calves weighing 80 to 240 kg to
      study the long-term nutritional regulation of circulating IGF-I, thyroxine (T4),
      and triiodothyronine (T3). The two experiments were similar in design but were
      performed with calves of two live weight ranges: 80 to 160 kg (Exp. 1) and 160 to
      240 kg (Exp. 2). In each experiment, 36 calves were allocated to one of 12
      dietary treatments, which consisted of six protein intake levels at each of two
      energy intake levels. Digestible protein intakes ranged between .90 and 2.72 g N
      x BW(-.75) x d(-1) in Exp. 1 and between .54 and 2.22 g N x BW(-.75) x d(-1) in
      Exp. 2. The energy intake levels were kept constant on a protein-free basis;
      increased energy intakes were realized by increasing energy intake from fat and
      carbohydrates in a fixed ratio. The digestible protein-free energy intakes were
      663 and 851 kJ x BW(-.75) x d(-1) in Exp. 1 and 564 and 752 kJ x BW(-.75) x d(-1)
      in Exp. 2. Blood samples were taken 5 to 6 h after feeding once every 14 d until
      the calves reached their target weight. In both experiments, plasma IGF-I and T4
      concentrations increased with increasing protein intake (P < .01), but they were
      unaffected by protein-free energy intake (P > .10). In both experiments, plasma
      T3 levels were markedly higher at the high protein-free energy intake level (P <
      .01) and increased slightly with increasing protein intake in Exp. 1 (P = .19)
      and Exp. 2 (P < .01). Results of these experiments suggest the involvement of IGF
      I in the response of protein deposition to increased protein intakes and the
      involvement of the active thyroid hormone T3 in the response of protein
      deposition to increased protein-free energy intakes.

PMID- 9621942
TI  - Effect of protein and protein-free energy intake on myofibrillar protein
      degradation in preruminant calves of 120 and 200 kilograms of live weight.
AB  - We studied the effect of protein and protein-free energy intake on the
      degradation rate of myofibrillar protein in preruminant calves in two
      experiments. Both experiments were similar in design but were performed with two
      live weight ranges: 80 to 160 kg (Exp. 1) and 160 to 240 kg (Exp. 2). In each
      experiment, calves were allocated to either an initial slaughter group or to one
      of 12 treatments (three calves per treatment), which consisted of six protein
      intake levels at each of two protein-free energy intake levels. Calves were
      slaughtered and analyzed for body composition when they had reached the target
      weight. A balance trial was performed when calves had reached 120 and 200 kg BW
      in Exp. 1 and 2, respectively. Myofibrillar protein degradation rate was measured
      by the urinary excretion of 3-methylhistidine. Correction of 3-methylhistidine
      excretion for myofibrillar protein mass was performed based either on the urinary
      creatinine excretion rate or on estimated body composition during the balance
      trial. In both experiments, fractional rates of myofibrillar protein degradation
      increased with increasing protein intake (P < .01). Fractional degradation rates
      increased with increasing protein-free energy intake in Exp. 1 (P < .10) and in
      Exp. 2 (P < .05). We conclude that the increased protein deposition rates,
      reported earlier, induced by nutrient intake are accompanied by increased
      myofibrillar protein degradation rates. Furthermore, we consider urinary
      creatinine excretion to be unreliable as an estimator of myofibrillar protein
      mass in experiments in which a large range of nutrient intakes is applied.

PMID- 9621943
TI  - Recombinant bovine somatotropin (rbST) administration to creep-fed beef calves
      increases muscle mass but does not affect satellite cell number or concentration
      of myosin light chain-1f mRNA.
AB  - Our objective in this study was to determine the effect of recombinant bovine
      somatotropin (rbST) on indices of muscle development in creep-fed beef calves.
      Crossbred steer calves were assigned to one of two treatment groups: control
      (sham-injected; n = 12) or rbST-treated (.09 mg x kg(-1) x d(-1); n = 12). Calves
      were injected every 14 d starting at d 28 of age and were weaned at 205 d of age.
      Supplemental creep feed was supplied free access to all calves to compensate for
      an expected increased protein and energy requirement in calves given rbST. Biopsy
      (d 100) and slaughter (d 206) samples of semitendinosus muscle were evaluated for
      satellite cell, myofiber nuclei numbers, and myosin light chain (MLC-1f) mRNA
      quantification. Myofiber nuclei and satellite cell numbers per 100 myofibers and
      MLC-1f mRNA:rRNA ratios at 100 and 206 d of age were not different (P > .10)
      between control and rbST-treated calves. Total gain, ADG, quality grade, femur
      length, percentage kidney, pelvic, and heart fat, dressing percentage, plasma IGF
      I, and plasma urea nitrogen concentrations did not differ (P > .10) between
      control and rbST-treated calves. However, rbST-treated calves had larger
      longissimus muscle areas (P < .03), less marbling (P < .001), higher carcass
      conformation scores (P < .04), greater mass of separated muscle (P < .03), more
      ground meat (P < .01), and heavier carcass weights (P < .05) than control calves.
      Thus, rbST treatment increased muscle characteristics while nuclei number and MLC
      1f mRNA concentrations remained the same, implying that the additional muscle
      growth was in a normal fashion.

PMID- 9621944
TI  - Temporal change in skeletal muscle IGF-I mRNA abundance and nitrogen metabolism
      responses to abomasal casein infusion in steers.
AB  - Skeletal muscle IGF-I and alpha-actin mRNA responses to increased amino acid
      availability were investigated in young, rapidly growing steers. Four Holstein
      steers (208 kg BW) were surgically implanted with an abomasal cannula and jugular
      catheters and allowed 2 wk to recover. Steers were offered hourly a 43:57
      forage:concentrate diet at 95% of ad libitum intake supplemented with continuous
      abomasal infusion of glucose (to replace 12.5% of metabolizable ad libitum energy
      intake) for 13 d before the start of abomasal infusion of 67 g of casein N/d.
      Biopsies of the liver and both semimembranosus muscles were removed and frozen in
      liquid N, and casein infusion was begun. Muscle biopsies were collected at 8, 16,
      24, and 48 h, and on d 7 and 14. Nitrogen balance increased from 23.6 to 71.5 g/d
      (P < .001) within 24 h and remained elevated (mean = 58.4 g/d) during the 14 d of
      casein infusion. Plasma urea N increased from 4 to 9.5 mg/dL at 24 h and remained
      unchanged to d 14. Muscle IGF-I mRNA abundance increased to 215% of basal values
      at 16 h (P < .01), 244% of basal values at 24 h, and 222% of basal values at 48 h
      after initiation of casein infusion. Values reached a maximum of 274% of basal
      values on d 7 and then declined to near preinfusion levels on d 14. The IGF-I
      mRNA abundance was approximately 100 times higher in liver than in skeletal
      muscle and was not different on d 0 and 14. Although plasma IGF-I concentrations
      were numerically higher during the first 24 h of abomasal casein infusion, they
      were not significantly higher during the chronic phase of treatment. Plasma IGF
      binding protein (BP)-2 concentrations were higher at 16, 24, and 48 h after
      casein infusion was begun, but IGFBP-3 concentrations were not altered at these
      sampling times. Neither acute (first 24 h) nor chronic (daily) plasma insulin
      concentrations were altered by abomasal casein infusion. Plasma somatotropin
      concentrations were lower (P = .008) at 24 h of casein infusion and beyond.
      Results suggest that enhanced amino acid availability may modulate skeletal
      muscle protein synthesis and accretion through an autocrine or paracrine IGF-I
      influence.

PMID- 9621945
TI  - Porcine somatotropin improves growth in finishing pigs without altering calpain 3
      (p94) or alpha-actin mRNA abundance and has a differential effect on calpastatin
      transcription products.
AB  - The objective of this study was to determine whether the improvements in growth
      and efficiency of gain achieved by recombinant porcine somatotropin (pST) are
      associated with altered expression of the p94, calpastatin, or alpha-actin genes
      in porcine longissimus (LD) muscle. Forty-eight barrows (initial 64.2 to 67.4 kg
      BW) were assigned to four treatments (n = 12) arranged as a 2 x 2 factorial in a
      randomized complete block design. Factors were duration of treatment (3 or 6 wk)
      and pST administration (0 or 3 mg x pig(-1) x d(-1)). Plasma samples were
      obtained 24 h after the first pST injection and at the end of the each treatment
      period for assays of selected variables. The LD samples were obtained at 3 and 6
      wk of pST treatment. Northern blot analysis of calpastatin expression in LD
      muscle revealed three distinct transcription products of approximately 8.5 (CPST
      I), 5.5 (CPST II), and 2.5 (CPST III) kb; CPST II was reduced (P < .02) 33 and
      61% by pST at 3 and 6 wk, respectively, whereas CPST I and III were not
      influenced (P > .12). Neither alpha-actin nor p94 was responsive to pST
      injection. As expected, pST resulted in higher (50%, P < .02) plasma insulin
      within 24 h and one- and twofold higher (P < .01) concentrations at 3 and 6 wk,
      respectively. Glucose was increased (P < .01) at 3 (15%) and 6 (10%) wk, whereas
      urea nitrogen was reduced (32 to 36%, P < .01). The efficacy of pST was evident
      in that ADG was improved (P < .01) 11 to 13% independent of time. Likewise, feed
      intake was reduced (P < .01) 10 to 11% and gain: feed improved (P < .01)
      approximately 26% for pigs receiving pST independent of time. These data indicate
      that the enhanced muscle growth achieved by pST is not associated with altered
      expression of p94 or alpha-actin, or an increase in the abundance of any
      calpastatin transcription product.

PMID- 9621946
TI  - Lipoprotein and hormone-sensitive lipases in porcine adipose tissue.
AB  - Lipoprotein lipase (LPL) is an adipocyte enzyme that cleaves fatty acids from
      circulating lipoproteins. Fatty acids enter the cell to be oxidized or
      esterified. Hormone-sensitive lipase (HSL) is an adipocyte enzyme that cleaves
      fatty acids from intracellular triacylglycerol. The HSL is activated by
      phosphorylation. Assays for the two lipases are complex because the hydrophobic
      substrate, triacylglycerol, must be presented as a gum-based suspension or as a
      detergent-based emulsion to a relatively hydrophilic enzyme. A convenient, stable
      glycerol/phospholipid suspension of the substrate was used for measurement of
      porcine adipose tissue LPL and HSL in vitro. This substrate was excellent for
      LPL. It produced rates five times those using a more complex and less convenient
      gum-based substrate suspension. The LPL activity was released by heparin, had a
      pH optimum of approximately 8.5, was activated by serum, and was inhibited by
      NaCl and protamine. This LPL assay measures enzyme capacity. The same substrate
      was used to measure an adipose tissue lipase activity that had a pH optimum below
      7, was not activated by serum, and was not inhibited by NaCl or protamine. These
      are all characteristics of HSL. Despite the convenience, this substrate was not
      appropriate for porcine adipose tissue HSL because the rates were only 30 to 50%
      of those produced with a more complex, less convenient gum-based substrate
      suspension. Furthermore, incubation of enzyme or tissue slices with insulin, or
      agents that elevate cAMP concentration, did not modulate this lipase activity, as
      expected. These incubations poorly modulated LPL activity.

PMID- 9621947
TI  - The biology of leptin: a review.
AB  - Leptin, a 16-kDa protein secreted from white adipocytes, has been implicated in
      the regulation of food intake, energy expenditure, and whole-body energy balance
      in rodents and humans. The gene encoding leptin was identified by positional
      cloning and is the mutation leading to the profound obese phenotype of the ob/ob
      mouse. Exogenous administration of leptin to ob/ob mice leads to a significant
      improvement in reproductive and endocrine status as well as reduced food intake
      and weight loss. The expression and secretion of leptin is highly correlated with
      body fat mass and adipocyte size. Cortisol and insulin are potent stimulators of
      leptin expression, and expression is attenuated by beta-adrenergic agonists,
      cAMP, and thiazolidinediones. The role of other hormones and growth factors in
      the regulation of leptin expression and secretion is emerging. Leptin circulates
      specifically bound to proteins in serum, which may regulate its half-life and
      biological activity. Isoforms of the leptin receptor, members of the interleukin
      6 cytokine family of receptors, are found in multiple tissues, including the
      brain. Many of leptin's effects on food intake and energy expenditure are thought
      to be mediated centrally via neurotransmitters such as neuropeptide Y. Multiple
      peripheral effects of leptin have also been recently described, including the
      regulation of insulin secretion by pancreatic beta cells and regulation of
      insulin action and energy metabolism in adipocytes and skeletal muscle. Leptin is
      thought to be a metabolic signal that regulates nutritional status effects on
      reproductive function. Leptin also plays a major role in hematopoeisis and in the
      anorexia accompanying an acute cytokine challenge. The profound effects of leptin
      on regulating body energy balance make it a prime candidate for drug therapies
      for humans and animals.

PMID- 9621948
TI  - Effects of alpha-tocopherol on metmyoglobin formation and reduction in beef from
      cattle fed soybean or cottonseed meal diets.
AB  - Hereford-Angus crossbred heifers were fed a cottonseed meal-based diet containing
      gossypol (14 mg free gossypol x kg body wt(-1) x d(-1); CSM), a soybean meal
      based diet (SBM), or alpha-tocopherol-supplemented diets (4,036 IU vitamin E x
      heifer(-1) x d(-1) for 90 d; CSM+E and SBM+E). The effects of diet on color
      stability and aerobic metmyoglobin reducing ability of beef longissimus lumborum
      (LL) and psoas major (PM) were evaluated. The CSM containing gossypol did not
      affect alpha-tocopherol concentration, a* value, or hue angle value of beef
      muscles obtained from control or vitamin E-supplemented cattle compared to their
      SBM counterparts. Vitamin E supplementation increased endogenous alpha-tocopherol
      concentrations and color stability in LL and PM muscles compared with controls
      from either diet (P < .05). In the aerobic metmyoglobin reducing ability study,
      LL and PM muscles were stored in 1% O2:99% N2 (a pigment-oxidizing atmosphere)
      for 48 h and subsequently stored aerobically for an additional 48 h. Within the
      LL, alpha-tocopherol supplementation delayed metmyoglobin formation in LL exposed
      to 1% O2 (P < .05). Within the PM, no differences in metmyoglobin formation were
      found between controls and vitamin E treatments in SBM or CSM diets. Relative
      aerobic metmyoglobin reduction was the same (P > .05) in LL and PM muscles within
      SBM or CSM diets for control and vitamin E treatments. Alpha-tocopherol did not
      seem to affect metmyoglobin aerobic reducing ability in LL and PM muscles.

PMID- 9621949
TI  - Effect of prerigor freezing and postrigor calcium chloride injection on the
      tenderness of callipyge longissimus.
AB  - The effect of rapid prerigor freezing and postrigor freezing and postrigor
      calcium chloride injection on the tenderness of callipyge longissimus was
      studied. Ewe and wether lambs (n = 49; 1/2 Dorset x 1/2 Romanov) were grain-fed
      and slaughtered at approximately 250 d of age. Based on leg conformation scores,
      23 of the carcasses had the callipyge phenotype. Within each phenotype,
      approximately one-half of the carcasses were chilled conventionally (24 h at -2
      degrees C). At approximately 17 min postmortem, the remaining carcasses were
      submersed in liquid nitrogen for 15 min and then held at -2 degrees C for 4 d. At
      1 d postmortem for carcasses chilled conventionally and at 4 d postmortem for
      carcasses frozen in liquid nitrogen, the longissimus muscles from both sides were
      removed. The longissimus from one side of each carcass was vacuum-packaged and
      aged (1 degrees C) conventionally for 7 or 14 d. The remaining muscles were
      injected with a 2.22% solution of food-grade calcium chloride at 5% by weight,
      vacuum-packaged, and aged as above. Liquid nitrogen freezing was effective in
      limiting sarcomere shortening (1.99 vs 1.63 microm; P < .05). Warner-Bratzler
      shear force values of callipyge longissimus were 222 and 232% of that of normal
      longissimus after 7 and 14 d postmortem, respectively (P < .001). Also, trained
      panel tenderness rating was decreased by 49.4% in untreated callipyge longissimus
      after 14 d postmortem. Liquid nitrogen, calcium chloride injection and their
      combination did not affect d-14 longissimus shear force and sensory tenderness
      for normal lambs because untreated muscles were already tender. Liquid nitrogen
      freezing improved the shear force and sensory tenderness rating of callipyge
      longissimus by 30 and 86.2% after 14 d postmortem, respectively. Calcium chloride
      injection improved the shear force and sensory tenderness of callipyge
      longissimus by 36.7 and 86.2% after 14 d postmortem, respectively (P < .001). The
      most effective treatment for mitigating the callipyge effect on tenderness was
      the combination (freezing and calcium chloride injection) treatment, which
      improved the shear force and sensory tenderness by 51.2 and 124.2% after 14 d
      postmortem, respectively (P < .001). We conclude that either treatment can
      effectively mitigate the negative effect of callipyge phenotype on longissimus
      tenderness. Callipyge lamb carcasses subjected to the combination of prerigor
      liquid nitrogen freezing, postrigor calcium chloride injection, and 14 d
      postmortem storage had tenderness similar (P > .05) to that of normal, untreated
      carcasses after 14 d of postmortem storage.

PMID- 9621950
TI  - Technical note: a technique for inserting a T-cannula into the distal ileum of
      pregnant sows.
AB  - Our objective was to develop a technique for cannulating the terminal ileum in
      pregnant sows and to evaluate the usefulness of this procedure in digestibility
      studies in pregnant and lactating sows. A simple T-cannula was inserted into the
      terminal ileum approximately 15 cm cranial to the ileo-cecal valve in a total of
      15 multiparous sows at d 40 (+/- 5 d) of pregnancy. All cannulated sows recovered
      quickly after the surgery and within 3 d they were eating normally. Elevated body
      temperatures were not registered in any sows, and clinical problems related to
      the surgery were not observed. At farrowing, normal litters were born, and number
      of stillborn pigs, number of live born pigs, and daily litter weight gain were
      not affected by the cannulations (P > .05). Of the 15 sows originally cannulated,
      11 sows were used for collection of digesta during gestation and the following
      lactating period. Eight sows were rebred after weaning, and five sows were rebred
      after the second lactation period and kept for another cycle. Blockage of the
      cannulas never occurred, and no serious problems were associated with digesta
      collections. The experiment demonstrated that pregnant sows can be prepared with
      a simple T-cannula in the distal ileum and that the cannula can be maintained in
      sows throughout the reproductive cycle. Hence, the procedure provides a tool for
      obtaining digesta from pregnant and lactating sows for nutrition studies.

PMID- 9621951
TI  - The use of synthetic lysine in the diet of lactating sows.
AB  - We conducted an experiment to determine the proportion of the lysine requirement
      of lactating sows that can be met using L-lysine x HCl. A total of 247 Pig
      Improvement Company (PIC) sows (parity one to four) were randomly allotted to one
      of five experimental diets containing .79% apparently digestible lysine. The
      first four diets contained 0, .075, .150, and .225% L-lysine x HCl replacing the
      intact lysine, primarily derived from soybean meal. Dietary crude protein was
      reduced from 17.9 to 16.9, 15.8, and 14.8% respectively. The fifth diet contained
      .174% L-lysine x HCl (15.5% CP) with added synthetic methionine, threonine, and
      tryptophan to restore the ratios of these amino acids to lysine to those in the
      control diet with no synthetic amino acids. The average lactation length was 15.7
      +/- .3 d. Diet did not affect ADFI, sow backfat loss, sow loin eye area loss, or
      weaning-to-mating interval. Sows consumed an average of 4.6 kg/d and were
      provided 36 g/d of digestible lysine. Replacing soybean meal with increasing
      levels of L-lysine x HCl did not affect sow weight change. The number of pigs
      weaned decreased and preweaning mortality increased linearly (P = .08) with
      increasing levels of L-lysine x HCl. Litters from sows fed the .174% L-lysine x
      HCl with added methionine, threonine, and tryptophan grew slower and had a higher
      mortality rate than litters from sows fed no synthetic amino acids (P < .05). The
      addition of synthetic methionine, threonine, and tryptophan to the .174% L-lysine
      x HCl diet did not improve litter growth rate, but it did increase preweaning
      mortality (P = .05) and decrease the number of pigs weaned (P = .06) compared to
      the .15% L-lysine x HCl with no additional synthetic amino acids. These additions
      also resulted in an increased sow weight loss (P = .10). These results suggest
      that when more than .075% L-lysine x HCl is used to meet the lysine requirement
      preweaning mortality is increased and the number of pigs weaned is decreased.
      Supplementation with methionine, threonine, and tryptophan failed to ameliorate
      the negative response associated with L-lysine x HCl, which suggests that other
      amino acids may be limiting.

PMID- 9621952
TI  - Hormonal profiles of callipyge and normal sheep.
AB  - Five sheep expressing the callipyge gene, which causes muscle hypertrophy, were
      compared with five normal sheep to determine whether endocrine differences
      existed between genotypes. Blood samples were taken at 15-min intervals for 6 h
      to measure serum concentrations of growth hormone and insulin. Thyroxine and IGF
      I levels were determined in single samples. No differences were found in mean
      serum growth hormone concentrations, growth hormone pulse amplitude, or pulse
      frequency (P > .3). Insulin concentrations were not different between genotypes
      before or after feeding (4.5 +/- 1.3 ng/mL callipyge vs 4.9 +/- 1.7 ng/mL normal,
      P > .4). The IGF-I concentrations did not differ (273.8 +/- 17.6 ng/mL callipyge
      vs 261.4 +/- 12.3 ng/mL normal). Serum thyroxine concentrations also were not
      different (5.9 +/- 2.3 microg/mL for callipyge vs 5.1 +/- 2.1 microg/mL normal, P
      > .3). In a separate experiment, five ewe lambs with and five without the
      callipyge gene were stressed to determine whether the adrenocortical response to
      stress differed between genotypes. Blood samples were taken at 15-min intervals
      for 2 h before, during, and after restraint stress. Restraint increased serum
      cortisol concentrations in both groups (P < .001), but genotypes did not differ
      at any time (P > .3). These results suggest that differences in muscling are not
      due to differences in systemic hormone secretion. The results of the second
      experiment indicate that callipyge and normal sheep have similar adrenocortical
      responses to stress.

PMID- 9621953
TI  - Reproductive hormonal responses to ergotamine and ergonovine in cows during the
      luteal phase of the estrous cycle.
AB  - We conducted research to evaluate whether ergot alkaloids associated with
      endophyte-infected tall fescue could alter plasma concentrations of hormones
      important to reproductive function in cows. Six primiparous, estrous-cycling
      Holstein cows nursing calves received single i.v. injections of ergotamine
      tartrate, ergonovine maleate, or saline vehicle in a simple cross-over design.
      Each cow received one compound per estrous cycle, d 15 or 16 after estrus, and
      all compounds over three estrous cycles. Blood samples were collected at 20-min
      intervals for 40 min before and 240 min after treatments to assess plasma
      concentrations of prolactin, LH, FSH, and the response by PGF2alpha metabolite
      13,14-dihydro-15-keto-prostaglandin F2alpha (PGFM). Ambient temperature and
      respiratory rates were measured hourly. Ambient temperature averaged 26 degrees C
      during data collection. Treatment x time was a significant source of variation
      for respiration rate and plasma concentrations of every hormone evaluated except
      FSH. Ergotamine elevated (P < .01) respiration rates 2 to 4 h after treatment.
      Ergotamine and ergonovine reduced (P < .001) plasma concentrations of prolactin
      for 2 to 4 h after treatment compared to concentrations before treatment. Plasma
      concentrations of LH were lowered (P < .01) by ergonovine during the 3rd h after
      treatment and by ergotamine during the 4th h after treatment. Most cows exhibited
      secretory PGFM responses after ergotamine and ergonovine treatments compared with
      an absence of a PGFM response in all cows after saline (P < or = .01). Results
      indicated that ergot alkaloids implicated as causative agents for fescue
      toxicosis can alter plasma concentrations of reproductive hormones during the
      late luteal phase of the estrous cycle in cows.

PMID- 9621954
TI  - Comparative effects of insulin and porcine somatotropin on postweaning follicular
      development in primiparous sows.
AB  - We compared the effects of exogenous insulin and porcine ST (pST) on follicular
      development after weaning. Crossbred primiparous sows received saline (1.5 mL
      i.m.; n = 9), insulin (.4 IU/kg BW s.c.; Eli Lilly Lente Iletin II; n = 10), or
      pST (40 microg/kg BW i.m.; n = 10) from d 1 to 5 after weaning (d 0). Ovaries
      were collected, the diameter of each follicle > or = 2 mm was measured, and fluid
      from the 20 largest follicles was assessed for IGF-I, IGF binding proteins
      (IGFBP), estradiol, progesterone, and testosterone. The total number (27.7, 25.3,
      and 29.1 for saline, insulin, and pST, respectively; SEM = 3.2) and average
      diameter (4.7, 5.2, and 5.5 mm for saline, insulin, and pST treatments,
      respectively; SEM = .3 mm) of ovarian follicles were not affected by insulin or
      pST treatment. The pST and insulin increased follicular fluid estradiol and
      testosterone in medium and large follicles compared to fluid from saline-treated
      sows, but the increase was greater for insulin than for pST treatment (treatment
      x size interaction, P < .01). Similarly, progesterone concentrations in
      follicular fluid were higher in medium and large follicles after insulin
      treatment, and pST treatment induced higher progesterone concentrations in small
      follicles and increasingly lower concentrations of progesterone in medium and
      large follicles (treatment x size interaction, P < .0007) compared to saline
      treatment. Follicular fluid IGF-I was greater (treatment x health interaction, P
      < .0001) in atretic and nonatretic follicles from pST-treated sows than in those
      from insulin- and saline-treated sows. Follicular fluid IGFBP-2 (tendency, P <
      .07) and IGFBP, possibly representing IGFBP-5 (30 kDa) and IGFBP-4 (22 kDa), were
      higher in atretic follicles than in nonatretic follicles (P < .05), whereas IGFBP
      3 was not influenced by health status. The 30- and 22-kDa IGFBP were also
      influenced by treatment, increasing due to pST compared with saline or insulin
      treatments (P < .008). Follicular fluid IGFBP-2 and IGFBP-3 were not influenced
      by treatment. In conclusion, pST and insulin positively influenced follicular
      steroidogenesis and possibly follicular development, although through different
      mechanisms.

PMID- 9621955
TI  - Uterine and ovarian responses to puberty induction and pregnancy in prepubertal
      gilts.
AB  - We evaluated the effect of age on response to puberty induction in gilts.
      Sequential treatment with a commercial gonadotropin mixture (400 IU PMSG, 200 IU
      hCG) followed 96 h later with hCG (500 IU) was used to induce follicular growth
      and ovulation, respectively. In the first experiment, gilts (84, 104, 124, 144,
      and 164 d old) were used. Peripheral blood was collected on d 0 (before
      treatment) and on d 2, 3, 4, 8, and 16 after treatment. On d 16, all gilts were
      hysterectomized, uterine flushings were collected, and uterine weight (UTWT) and
      length (UTLG) were measured. For treated gilts, UTWT, UTLG, number of corpora
      lutea (CL), peripheral progesterone (P4) on d 16, and estradiol (E2) on d 4
      increased (P < .05) linearly with age. Uterine luminal PGE (P < .05) and PGF (P =
      .07), expressed per UTWT, responded quadratically with age; gilts treated at 124
      d of age or older showed decreased amounts. Overall, the number of CL correlated
      positively (P < .01) with UTWT and P4 on d 8 and 16. Peripheral P4 on d 4, 8, and
      16 (P < .10) and E2 on d 0 and 4 (P < .01) were correlated positively with
      uterine weight on d 16. Gilts induced to ovulate at 104 and 144 d of age had
      heavier and longer uteri (P < .01), more P4 on d 8 and 16 (P < .05), and more E2
      on d 2 (P < .1) and 4 (P < .05) than controls at the same age. The second
      experiment evaluated pregnancy success for gilts induced to ovulate at 116 vs 151
      d of age. The effects of induction of two consecutive estrous cycles also were
      evaluated. Two of seven (28.6%) and four of nine (44.4%) gilts first treated when
      116 and 151 d old but none of seven gilts treated at 96 and 116 d of age were
      pregnant 60 d after insemination. Results indicate that induction of a prior
      cycle did not improve pregnancy rates. However, some gilts in this population
      maintained pregnancies to 60 d when induced to ovulate and inseminated at 120 d
      of age.

PMID- 9621956
TI  - Predicting forage indigestible NDF from lignin concentration.
AB  - We used chemical composition and in vitro digestibility data from temperate and
      tropical forages to develop relationships between indices of lignification and
      forage indigestible NDF. Neutral detergent fiber indigestibility increased
      nonlinearly as the lignin concentration of the NDF increased. Differences in
      estimated indigestible NDF using equations developed for a specific forage class
      (C3 and C4 grasses and legumes) were small and are probably not biologically
      significant when compared to those estimated from a common equation. Selected
      equations were compared with the Cornell Net Carbohydrate and Protein System
      (CNCPS) for the prediction of ADG. The linear equation (2.4 times NDF lignin
      content) used by the CNCPS and the Beef NRC had some of the largest errors due to
      mean bias. A log-log model [4.37 x (lignin/NDF)(.84)] provided the best
      combination of low total prediction error, low mean bias, and minimal error due
      to regression bias when permanganate lignin was used. A similar equation based on
      sulfuric acid lignin [6.17 x (lignin/NDF)(.77)] also met the above criteria.
      These equations then were evaluated with the CNCPS model against animal growth
      data from diets ranging in forage quality. Regardless of the equation used for
      predicting unavailable fiber, the CNCPS underpredicted daily gain, with mean
      biases ranging from -.10 to -.22 kg/d. Regression bias ranged from .13 to .14
      kg/d and the coefficients differed from unity (P = .0001). The new equations gave
      numerically lower energy allowable ADG by steers compared to the linear equation
      currently used by the CNCPS model. The estimates were lower due to a higher
      predicted indigestible NDF, which resulted in a lower estimated forage energy
      value.

PMID- 9621957
TI  - Effects of a dietary mixture of meat and bone meal, feather meal, blood meal, and
      fish meal on nitrogen utilization in finishing Holstein steers.
AB  - Our objective was to determine to what extent rate and efficiency of protein gain
      in finishing cattle can be enhanced by feeding an amino acid-balanced mixture of
      undegraded intake proteins. The Cornell Net Carbohydrate and Protein System
      (CNCPS) model was used to formulate a corn-based diet that would meet the rumen
      requirements for 410-kg large-framed steers with an estrogen implant and fed an
      ionophore. The CNCPS model was also used to formulate a highly undegradable
      intake protein (UIP) mixture from meat and bone meal, blood meal, fish meal, and
      hydrolyzed feather meal to provide the amino acids needed to supplement those
      derived from microbial protein to better meet amino acid requirements for growth.
      Four Holstein steers weighing 407 kg were offered a 90:10 concentrate-forage diet
      at hourly intervals at 95% of ad libitum intake. The steers were injected with
      500 microg of estradiol-17beta at 12-h intervals to mimic the effects of an
      estrogenic implant. Treatments planned consisted of inclusion of the UIP mixture
      at 0, 2.5, 5, and 7.5% of the diet DM. Dry matter intake was fixed at 6.4 kg/d,
      and DM digestibility was not significantly affected by varying the amount of UIP
      addition. Apparent digestibility of N increased (P = .011) from 63.8 to 65.8,
      70.7, and 71.5%, the amount of N absorbed increased (P = .001) from 73 to 84,
      100, and 106 g/d, and N balance increased (P = .003) from 20 to 30, 33, and 39
      g/d when UIP was fed at 0, 2.6, 5.2, and 7.8% of diet DM, respectively. The
      efficiency of N use increased 39.7%, and biological value increased 31.6% when
      the UIP mixture was added to the diet. Circulating concentrations of plasma urea
      N (PUN) were increased (P = .017) from 4.5 for the control diet to 5.7, 6.2, and
      6.1 mg/dL when the UIP mixture was added at 2.6, 5.2, and 7.8%, respectively.
      Corresponding IGF-I concentrations were also increased from 491 to 558 and 624
      ng/mL with 2.6 and 5.2% levels of UIP addition. Plasma glucose, NEFA, and insulin
      concentrations were not affected by feeding the UIP mix. The rate and efficiency
      of N use for growth improved with addition of an amino acid-balanced UIP mixture
      to the diet.

PMID- 9621958
TI  - Effect of energy source and escape protein on receiving and finishing performance
      and health of calves.
AB  - Two receiving and two finishing trials evaluated energy source and escape protein
      supplementation for calves. In receiving Trial 1, 398 calves (257 +/- 24 kg BW)
      were used in a 2 x 2 factorial arrangement of treatments. Energy sources were dry
      rolled corn (DRC) and wet corn gluten feed (WCGF); each was fed without or with
      supplemental escape protein (EP). Calves fed WCGF gained slower (P < .05) and
      consumed less DM (P < .01) than calves fed DRC. Feed efficiency improved (P <
      .10) with EP supplementation. In finishing Trial 1, 240 calves (305 +/- 21 kg BW)
      were used. The arrangement of treatments was the same as in receiving Trial 1.
      Calves fed DRC/WCGF tended (P = .15) to be more efficient and consumed less DM (P
      < .05) than calves fed DRC. In receiving Trial 2, 315 calves (252 +/- 23 kg BW)
      were fed diets similar to those fed in receiving Trial 1. Calves fed WCGF
      consumed less DM (P < .01), gained similarly (P > .15), and were more efficient
      (P < .10) than calves fed DRC. In finishing Trial 2, 320 calves (298 +/- 23 kg
      BW) were fed diets containing DRC, DRC/WCGF, high-moisture corn (HMC), HMC/WCGF,
      and DRC/HMC; each was fed without or with supplemental EP. An energy source x
      protein supplement interaction was detected for gain (P < .05) and efficiency (P
      < .01). Results suggest that WCGF has a NEg greater than DRC in receiving diets
      and a NEg similar to that of DRC but lower than that of HMC in finishing diets.

PMID- 9621959
TI  - Rapid communication: PCR-RFLP for MspI and NcoI in the ovine calpastatin gene.

PMID- 9621960
TI  - Rapid communication: the porcine Inter-alpha trypsin inhibitor-heavy chain 4
      (ITIH4) gene maps to chromosome 13.

PMID- 9621961
TI  - Rapid communication: identification of two microsatellite loci that map to
      porcine chromosome 3.

PMID- 9621962
TI  - Rapid communication: identification of two microsatellite loci that map to
      porcine chromosome 6.

PMID- 9621963
TI  - Magnetically labeled water perfusion imaging of the uterine arteries and of
      normal and malignant cervical tissue: initial experiences.
AB  - PURPOSE: The aim of this pilot study was to evaluate a magnetically labeled water
      perfusion imaging technique as a non-contrast-enhanced approach to demonstrate
      the uterine artery, its branches, and to assess the cervical uterine blood flow
      in healthy volunteers and in patients with advanced uterine cervical carcinoma
      (FIGO IIB-IVA). METHODS AND MATERIALS: Seven healthy volunteers (mean age, 29
      years) and twenty-two patients (mean age, 52 years) with advanced cancer of the
      uterine cervix (FIGO IIB-IVA) were prospectively examined by magnetically labeled
      water perfusion imaging at different inversion delay times (300-900 ms). The
      magnetic resonance imaging (MRI) findings of all patients were matched to the
      findings of contrast-enhanced dynamic MRI and multiple biopsies (n = 5) and/or
      surgical whole mount specimens (n = 17), which were available in all patients.
      RESULTS: The uterine artery was well visualized with short inversion delay times
      of 300-500 ms. It was characterized as single or multiple helical loops before
      dividing into its intracervical branches. The intracervical branching was
      observed at inversion delay times of 500-700 ms. With longer inversion delay
      times, arterial signal enhancement disappeared and cervical tissue enhancement
      was noted. Enhancement of benign tissue was observed at inversion delay times of
      1100-1700 ms and in malignant tissue at shorter inversion delay times of 900-1300
      ms. The maximum of this diffuse signal enhancement of benign tissue was seen at
      inversion delay times of 1500 ms (1100-1700 ms) in malignant tissue at
      significantly (p < 0.5) shorter inversion delay times of 1100 ms (900-1300 ms).
      CONCLUSION: Our preliminary results show that the vascular supply and blood flow
      of the normal uterine cervix and of advanced cervical cancer can be assessed by
      magnetically labeled water perfusion imaging and that malignant cervical tissue
      is earlier and stronger perfused than normal cervical tissue.

PMID- 9621964
TI  - Fetal and fetal brain volume estimation in the third trimester of human pregnancy
      using gradient echo MR imaging.
AB  - The Cavalieri method has been applied in combination with gradient echo magnetic
      resonance imaging (MRI) to investigate the increase in the volume of the fetus
      and fetal brain in the third trimester of pregnancy. Eighteen women with
      singleton pregnancies were recruited. Birthweights for the fetuses all lay within
      the 10-90th centile based on Liverpool data. A regression analysis, weighted
      using values derived from the coefficient of error predicted for each volume
      estimate, revealed a linear relationship between total fetal volume and
      gestational age (R2 = 0.88) and between fetal brain volume and gestational age
      (R2 = 0.71) during the third trimester. Fetal volume increased by an average of
      25.2 ml per day and fetal brain volume increased by an average of 2.3 mL per day.
      Fetal brain volume is on average a constant proportion (10%, SD = 2%) of total
      fetal volume throughout the third trimester. Volume data were also obtained for
      eight fetuses diagnosed as abnormal. The volume of seven of the eight abnormal
      fetuses fell outside the 95% confidence interval established from the data
      obtained for the normal fetuses. However, for only three of the eight abnormal
      fetuses did brain volume fall outside the 95% confidence interval established for
      normals, possibly due to brain sparing occurring in asymmetrical growth
      retardation. The volume of the fetus and fetal brain may be readily estimated
      directly using the Cavalieri method and magnetic resonance imaging. These
      parameters represent potentially useful information for assessing fetal growth.

PMID- 9621965
TI  - In vivo relaxation time measurements in the human placenta using echo planar
      imaging at 0.5 T.
AB  - This paper presents the first in vivo measurements of the nuclear magnetic
      resonance relaxation times T1 and T2 at 0.5 T in the human placenta from 20 weeks
      gestational age until term, in both normal and compromised pregnancies. T1
      measurements were performed by using both an inversion recovery sequence and the
      Look-Locher echo planar imaging (EPI) sequence on a total of 41 women with normal
      pregnancies and 11 women with compromised pregnancies. T2 measurements were
      performed by using a spin-echo EPI sequence on 36 women with normal pregnancies
      and 14 women with compromised pregnancies. In normal pregnancies, both the T1
      values measured with the inversion recovery sequence and the T2 values were found
      to decrease with gestational age, the linear regression results gave T1 = -9.1t +
      1538 r2 = 0.23 p = 0.03. T2 = -4.0t + 338 r2=0.47 p =410(-6) where t is the
      gestational age in weeks, and T1 and T2 are the relaxation times in milliseconds.
      T1 values measured very rapidly with the Look-Locher EPI sequence, but,
      therefore, with a much lower signal-to-noise ratio, showed no significant trends.
      The T1 values measured in the abnormal group were significantly lower than those
      measured in the normal group. Four out of eight patients with compromised
      pregnancies had placental T1 values lying outside the 90% confidence limits for
      the normal population based about the regression line, significantly more than
      expected by chance (p = 0.005). Ten out of fourteen of the T2 measurements in the
      abnormal group were below the regression line established for the normal group,
      with 4 lying below the 90% confidence interval, although these trends were only
      just significant (p = 0.06 and p = 0.03).

PMID- 9621966
TI  - Objective stenosis quantification from post-stenotic signal loss in phase
      contrast magnetic resonance angiographic datasets of flow phantoms and renal
      arteries.
AB  - In this study a semi-automated and observer-independent algorithm for quantifying
      post-stenotic signal loss (PSL) in three-dimensional phase-contrast (PC) magnetic
      resonance angiography (MRA) of patients with renal artery stenosis is presented.
      This algorithm was developed on MRA datasets of stenotic phantoms, included in a
      flow circuit with stationary flows. The length and the severity of the PSL
      (incorporating both the length and the degree of PSL) in the MRA datasets were
      proposed for quantifying the stenoses. The algorithm was tested in renal
      arteries; ten patients with renal artery stenosis and seven healthy volunteers
      were investigated. Digital subtraction angiography was performed in the patients
      and served as the gold standard. Stenosis severity showed better correlation with
      the severity of the PSL than with the length, both for in vitro and in vivo
      measurements. Spearman correlation coefficients (rs) showed statistically
      significant correlations between the severity of the PSL and parameters
      determined by digital subtraction angiography, i.e., percent diameter stenosis
      (rs = 0.90). The length of the PSL showed no correlation with the diameter
      stenosis (rs = 0.37). In conclusion, this study presents a semi-automated and
      observer-independent way of quantifying signal loss, and the severity of the PSL
      is proposed for quantifying stenoses, rather than the length of PSL.

PMID- 9621967
TI  - Multiphase segmented k-space velocity mapping in pulsatile flow waveforms.
AB  - The aim of the present study was to obtain the precision of flow measurement in
      breath-hold segmented k-space flow sequences. The results are based on studies of
      pulsatile flow in a phantom tube. The ultimate purpose is to use these sequences
      to measure coronary flow. In abdominal and cardiothoracic magnetic resonance
      imaging the image quality is degraded due to respiratory motion. In the segmented
      k-space acquisition method, one obtains many phase-encoding steps or views per
      cardiac phase. This shortens imaging time in the order of phase-encoding lines
      and makes it possible to image in a single breath-hold, thereby eliminating
      respiratory artefacts and improving edge detection. With breath-hold multiframe
      cine flow images it is possible to evaluate flow in all abdominal and
      cardiothoracic areas, including the coronary arteries. Our study shows that
      velocity curves shift in time when the number of k-space ky-lines per segment
      (LPS) are varied; this shift is linear as a function of LPS. The mean velocity
      Vmean in the center of mass of the pulsatile peak is constant (Vmean = 40.1 +/-
      2.9 cm/s) and time t = -10.1 x LPS + 268 (r = 0.993, p < 0.0001). Correlation
      between theoretical and experimental flow curves is also linear as a function of
      LPS: C = -0.977 * LPS (r = 0.987, p < 0.0001). It is concluded that velocity
      curves move with LPS and are smoothed when the breath-hold velocity mapping is
      used. The more LPS is gathered the more inaccurate results are. LPS 7 or more
      cannot be considered clinically relevant.

PMID- 9621968
TI  - MRI measurement of brain tumor response: comparison of visual metric and
      automatic segmentation.
AB  - An automatic magnetic resonance imaging (MRI) multispectral segmentation method
      and a visual metric are compared for their effectiveness to measure tumor
      response to therapy. Automatic response measurements are important for
      multicenter clinical trials. A visual metric such as the product of the largest
      diameter and the largest perpendicular diameter of the tumor is a standard
      approach, and is currently used in the Radiation Treatment Oncology Group (RTOG)
      and the Eastern Cooperative Oncology Group (EGOG) clinical trials. In the
      standard approach, the tumor response is based on the percentage change in the
      visual metric and is categorized into cure, partial response, stable disease, or
      progression. Both visual and automatic methods are applied to six brain tumor
      cases (gliomas) of varying levels of segmentation difficulty. The analyzed data
      were serial multispectral MR images, collected using MR contrast enhancement. A
      fully automatic knowledge guided method (KG) was applied to the MRI multispectral
      data, while the visual metric was taken from the MRI films using the T1
      gadolinium enhanced image, with repeat measurements done by two radiologists and
      two residents. Tumor measurements from both visual and automatic methods are
      compared to "ground truth," (GT) i.e., manually segmented tumor. The KG method
      was found to slightly overestimate tumor volume, but in a consistent manner, and
      the estimated tumor response compared very well to hand-drawn ground truth with a
      correlation coefficient of 0.96. In contrast, the visually estimated metric had a
      large variation between observers, particularly for difficult cases, where the
      tumor margins are not well delineated. The inter-observer variation for the
      measurement of the visual metric was only 16%, i.e., observers generally agreed
      on the lengths of the diameters. However, in 30% of the studied cases no
      consensus was found for the categorical tumor response measurement, indicating
      that the categories are very sensitive to variations in the diameter
      measurements. Moreover, the method failed to correctly identify the response in
      half of the cases. The data demonstrate that automatic 3D methods are clearly
      necessary for objective and clinically meaningful assessment of tumor volume in
      single or multicenter clinical trials.

PMID- 9621969
TI  - Functional magnetic resonance imaging of the basal ganglia and cerebellum using a
      simple motor paradigm.
AB  - Activation of cortical and subcortical motor areas of the brain, including
      primary motor cortex, supplementary motor area, basal ganglia and cerebellum,
      were successfully investigated in seven right-handed, normal volunteers during a
      simple, rapid, thumb flexion-extension task using functional magnetic resonance
      imaging. A multi-slice echo-planar imaging sequence was used to cover the entire
      brain. A signal increase varying from 2% to 6% was observed for the different
      regions involved in the motor task. Moving the non-dominant thumb was associated
      with a more bilateral activation pattern in both putamen and cerebellar regions.
      This study demonstrates the capability of functional magnetic resonance imaging
      to delineate simultaneously many activated brain areas that are commonly thought
      to be involved in the performance of motor tasks.

PMID- 9621970
TI  - Quantifying and comparing region-of-interest activation patterns in functional
      brain MR imaging: methodology considerations.
AB  - The general aims of functional brain magnetic resonance imaging (fMRI) studies
      are to ascertain which areas of the brain are activated during a specific task,
      the extent of this activation, whether different groups of subjects demonstrate
      different patterns of activation, and how these groups behave in different tasks.
      Many steps are involved in answering such questions and if each step is not
      carefully controlled the results may be influenced. This work has three
      objectives. Firstly, to present a technique for quantitatively evaluating methods
      used in functional imaging data analysis. While receiver-operator-characteristic
      (ROC) analysis has been used effectively to evaluate the ability of post
      processing algorithms to detect true activations while rejecting false
      activations, it is difficult to adapt such a technique for comparisons of methods
      for quantitating activations. We present a technique based on the ANOVA, between
      two or more regions of interest (ROIs), subject groups, or activation tasks, over
      a range of statistical thresholds, which reveals the sensitivity of different
      activation quantification metrics to noise and other variables. Secondly, we use
      this technique to compare two methods of quantifying localized brain activation.
      There are numerous ways of quantifying the amount of activation present in a
      specific region of the brain in an individual subject. We compare the pixel count
      approach, which simply counts the number of pixels above an arbitrary statistical
      threshold, with an approach based on the sum of t-values above the same arbitrary
      t-value threshold. Finally, we examine the sensitivity of the results from an
      analysis of variance, to user defined parameters such as threshold and region of
      interest size. Both simulated and real functional magnetic resonance data are
      used to demonstrate these techniques.

PMID- 9621971
TI  - In vitro model of arterial stenosis: correlation of MR signal dephasing and trans
      stenotic pressure gradients.
AB  - PURPOSE: Turbulent flow just distal to stenoses causes signal loss (dephasing) on
      magnetic resonance angiography (MRA). This study correlates dephasing with trans
      stenotic pressure gradients in an in vitro model of arterial stenosis. MATERIALS
      AND METHODS: Three-dimensional (3D) phase contrast, 2D time-of-flight, and 3D
      spoiled gradient echo MRA with/without gadolinium and varied echo time were
      performed for a system consisting of a peristaltic perfusion pump and a silastic
      vessel with stenoses of varying caliber. Length and diameter of dephasing jets
      were measured, and volumes calculated at varying pressure gradients and echo
      times, then correlated with percentage cross-sectional area stenosis as measured
      by conventional angiography. RESULTS: Dephasing occurred in all sequences at
      pressure gradients of > or =4 mmHg (1 mmHg = 133 Pa) and stenoses of greater than
      70%, and varied directly with pressure gradient. The dephasing was greatest for
      3D phase contrast (PC). Gadolinium did not diminish dephasing. CONCLUSIONS: MRA
      signal dephasing at stenoses varies directly with pressure gradient. MRA may
      provide a non-invasive means for determining the hemodynamic significance of
      arterial stenoses.

PMID- 9621972
TI  - Automated detection and characterization of multiple sclerosis lesions in brain
      MR images.
AB  - In the present study an automatic algorithm for detection and contouring of
      multiple sclerosis (MS) lesions in brain magnetic resonance (MR) images is
      introduced. This algorithm automatically detects MS lesions in axial proton
      density, T2-weighted, gadolinium enhanced, and fast fluid attenuated inversion
      recovery (FLAIR) brain MR images. Automated detection consists of three main
      stages: (1) detection and contouring of all hyperintense signal regions within
      the image; (2) partial elimination of false positive segments (defined herein as
      artifacts) by size, shape index, and anatomical location; (3) the use of an
      artificial neural paradigm (Back-Propagation) for final removal of artifacts by
      differentiating them from true MS lesions. The algorithm was applied to 45 images
      acquired from 14 MS patients. The algorithm's sensitivity was 0.87 and the
      specificity 0.96. In 34 images, 100% of the lesions were detected. The algorithm
      potentially may serve as a useful preprocessing tool for quantitative MS
      monitoring via magnetic resonance imaging.

PMID- 9621973
TI  - Serial precision of metabolite peak area ratios and water referenced metabolite
      peak areas in proton MR spectroscopy of the human brain.
AB  - The precision of cerebral proton magnetic resonance spectroscopy (MRS)
      measurements is critical both in the clinical setting and for research purposes.
      Marshall et al. have recently concluded that "disappointing in vivo
      repeatability...is likely to limit" the ability of MRS to detect modest changes.
      We present here a comprehensive study of the precision of short- and long-term
      metabolite peak area ratios and water referenced metabolite peak areas for long
      echo time point resolved spectroscopy (PRESS) spectra (repetition time (TR) =
      2000 ms, echo time (TE) = 136 ms) acquired from the occipital lobes of normal
      volunteers and a phantom using a conventional whole body 1.5 T MR system and
      conventional acquisition and analysis protocols. Short-term in vitro precision
      determined by five repeat scans on five occasions was excellent as measured by a
      mean coefficient of variation (NAA/Cho = 1.3%, NAA/Cr + PCr = 1.0%, Cho/Cr + PCr
      = 1.6%, NAA/H2O = 0.5%, Cho/H2O = 1.2%, Cr + PCr/H2O = 0.8%). Long term in vitro
      precision using 100 spectra acquired over 2 years was also very good (NAA/Cho =
      2.7%, NAA/Cr + PCr = 1.4%, Cho/Cr + PCr = 2.2%, NAA/H2O = 1.5%, Cho/H2O = 2.4%,
      Cr + PCr/H2O = 1.5%). Short-term in vivo precision determined by five repeat
      scans in a single scanning session on eight subjects was also excellent (NAA/Cho
      = 5.2%, NAA/Cr + PCr = 3.0%, Cho/Cr + PCr = 6.6%, NAA/H2O = 1.4%, Cho/H2O = 4.9%,
      Cr + PCr/H2O = 2.7%) and only worsened slightly for long-term in vivo precision
      determined by five repeat scans on eight subjects over 3 months (NAA/Cho = 5.2%,
      NAA/Cr + PCr = 4.8%, Cho/Cr + PCr = 7.7%, NAA/H2O = 2.5%, Cho/H2O = 6.4%, Cr +
      PCr/H2O = 3.8%). We attribute the excellent precision reported here to the use of
      highly automated techniques for voxel shimming, water suppression and peak area
      measurements. These results allow us to repudiate Marshall's assertion regarding
      disappointing repeatability of in vivo MRS.

PMID- 9621974
TI  - Functional magnetic resonance imaging in intact plants--quantitative observation
      of flow in plant vessels.
AB  - Quantitative magnetic resonance (MR) images of flow velocities in intact corn
      plants were acquired using magnetization-prepared MR microscopy. A phase contrast
      flow imaging technique was used to quantitate water flow velocities and total
      volume flow rates in small xylem vessels. The simultaneous measurement of the
      transpiration of the whole plant was achieved by using a closed climate chamber
      within the MR magnet. The total volume flow rate and the transpiration values
      were in close correlation. Functional magnetic resonance imaging in intact plants
      was performed by light stimulation of the transpiration inside of the magnet. The
      change in the flow velocities in the xylem vessels of single vascular bundles was
      in correlation with the changes in the transpiration. Significant differences
      were observed between the xylem vessels in different vascular bundles.
      Furthermore, flow velocity measurements were performed on excised plant stems and
      visualized by the uptake of the MR contrast agent, gadolinium-diethylenetriamine
      pentaacetic acid (Gd-DTPA). A comparison between the phase contrast flow imaging
      and the contrast media uptake showed to be in good agreement with each other.

PMID- 9621975
TI  - Magnetic resonance imaging with gadolinium-diethylenetriamine pentaacetic acid is
      useful in assessment of tubal patency in a patient with iodine-induced
      hypothyroidism.
AB  - A 32-year-old woman presented for evaluation of primary infertility. Because she
      had a history of iodine-induced hypothyroidism, conventional
      hysterosalpingography was contraindicated. Tubal patency was assessed by magnetic
      resonance imaging (MRI) after infusion of gadolinium-diethylenetriamine
      pentaacetic acid (Gd-DTPA). Visualization of the contrast medium in the
      peritoneal cavity revealed tubal patency. Our case indicates that MRI with
      gadolinium-diethylenetriamine pentaacetic acid is a safe, simple, and easy way to
      confirm that at least one tube is patent when a patient is at risk for
      hysterosalpingography. To our knowledge, this is the first report that tubal
      patency was diagnosed on MRI.

PMID- 9621976
TI  - Metastatic gastric leiomyoblastoma: a case report.
AB  - Gastric leiomyoblastoma is a rare entity. In this report, we describe the
      magnetic resonance (MR) appearance of a recurrent gastric leiomyoblastoma 14
      years after initial presentation. This tumor was heterogeneous and moderately low
      signal intensity on T1-weighted images and heterogeneous and moderately high
      signal intensity on T2-weighted images. The tumor also contained foci of low
      signal intensity on the post gadolinium images, consistent with areas of
      necrosis. The mass enhanced mildly and increased in enhancement on the delayed
      images, consistent with a hypovascular mass. Multiple liver metastases were
      noted. Magnetic resonance findings were confirmed with surgical specimens.

PMID- 9621977
TI  - A case of effusive-constructive pericarditis: an efficacy of GD-DTPA enhanced
      magnetic resonance imaging to detect a pericardial thickening.
AB  - A 38-year-old man underwent pericardiectomy because of effusive-constrictive
      pericarditis. The gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA)
      enhanced magnetic resonance imaging showed pericardial thickening separate from
      the effusion, which could not be shown by unenhanced computed tomography. Gd-DTPA
      enhanced magnetic resonance imaging could be useful for the early detection of
      effusive-constrictive pericarditis.

PMID- 9621978
TI  - A comparison of laboratory and epidemiologic approaches to pediatric research.

PMID- 9621979
TI  - Early high dose antioxidant vitamins do not prevent bronchopulmonary dysplasia in
      premature baboons exposed to prolonged hyperoxia: a pilot study.
AB  - The antioxidant vitamins ascorbic acid (AA) and alpha-tocopherol (alpha-TP)
      effectively inhibit oxygen free radical-induced lipid peroxidation. Using a
      premature baboon model of hyperoxia-induced bronchopulmonary dysplasia (BPD), we
      measured concentrations of AA, alpha-TP, and conjugated dienes (CD, marker of
      lipid peroxidation) in four animals (hyperoxic antioxidant group) receiving high
      dose antioxidant vitamin supplementation (AA, 100 mg x kg x(-1) x d(-1); alpha
      TP; 20 mg x kg x(-1) x d(-1)) and one animal receiving standard dose antioxidant
      vitamin supplementation (AA, 10 mg x kg x(-1) x d(-1); alpha-TP, 1 mg x kg x(-1)
      x d(-1)). Respiratory and histopathologic data were compared with data from 10
      historical animals exposed to hyperoxia (hyperoxic control group) and 11
      historical animals treated as required with oxygen (normoxic control group) who
      had received standard dose antioxidant vitamin supplementation. Compared with
      standard dose antioxidant vitamin supplementation, high dose antioxidant vitamin
      supplementation effectively raised AA concentrations in plasma (37 +/- 22
      micromol/L and 395 +/- 216 micromol/L, respectively) and tracheal aspirates (62
      +/- 35 micromol/L and 286 +/- 205 micromol/L, respectively), and alpha-TP
      concentrations in plasma (10.1 +/- 2.5 micromol/L and 24.6 +/- 17.5 micromol/L,
      respectively). However, there was no apparent effect on tracheal aspirate CD
      concentrations (482 +/- 333 micromol/L and 1050 +/- 1111 micromol/L,
      respectively), and respiratory parameters in the hyperoxic antioxidant group were
      comparable to those of the hyperoxic control group but significantly worse than
      in the normoxic control group. Finally, no protective effect of high dose
      antioxidant vitamin supplementation was noted at the histopathologic level.

PMID- 9621980
TI  - Nitric oxide increases the survival of rats with a high oxygen exposure.
AB  - The purpose of this study was to begin to examine the influence of inhaled NO on
      O2 toxicity. The survival of Sprague-Dawley rats exposed to >95% O2, >95% O2 + 10
      ppm NO, >95% O2 + 100 ppm NO, and >95% O2 + 3 ppm NO2 was determined. Survival at
      120 h was 2/24 in >95% O2, 2/12 in >95% O2 + 10 ppm NO, and 1/12 in >95% O2 + 3
      ppm NO2. Survival at 120 h was 21/30 in >95% O2 + 100 ppm NO (p < 0.01 compared
      with >95% O2). Three additional groups of rats were exposed for 60 h to: 21% O2,
      >95% O2, or >95% O2 + 100 ppm NO. The lungs were then assayed for total protein,
      reduced (GSH) and oxidized glutathione (GSSG), and 4-hydroxy-2(E)-nonenal. Both
      of the high O2 groups had significantly (p < 0.05) lower GSH/mg protein and
      GSH/GSSG ratios compared with the 21% O2 group. The >95% O2 group had a higher 4
      hydroxy-2(E)-nonenal/mg of protein than either the 21% O2 group (p < 0.05), or
      the >95% O2 + 100 ppm NO group (p < 0.05 compared with >95% O2, not different
      from the 21% O2 group). Additional groups of rats were exposed to either 21% O2,
      >95% O2, or >95% O2 + 100 ppm NO for 0, 24, 48, and 60 h. The lungs were examined
      for neutrophil accumulation, which was increased at 60 h in the two groups
      exposed to >95% O2, but adding NO had no effect. Thus, the overall result was
      that 100 ppm inhaled NO improved the survival of rats in high O2.

PMID- 9621981
TI  - Effects of hypoxia and reoxygenation on nitric oxide production and cerebral
      blood flow in developing rat striatum.
AB  - We investigated the role of nitric oxide (NO) in the regulation of regional
      cerebral blood flow (rCBF) during hypoxia and reoxygenation in developing rat
      striatum. The subjects were urethane-anesthetized 7- and 14-d-old rats. After 120
      min of baseline measurements, the rats received an i.p. injection of either
      saline (as a control) or an NO synthase inhibitor, N-nitro-L-arginine methyl
      ester (L-NAME, 30 mg/kg) 30 min before hypoxia. Then they were subjected to a 60
      min hypoxia in 8% O2, followed by a 60-min recovery in 21% O2. rCBF and NO
      concentration in the striatum were measured by laser Doppler flowmetry and an NO
      electrode throughout the experimental period. In the controls, rCBF decreased to
      93 +/- 3% of baseline during hypoxia and increased to 124 +/- 3% of baseline
      during reoxygenation in 7-d-old rats (n = 13), whereas rCBF increased during both
      hypoxia and reoxygenation in 14-d-old rats to 125 +/- 6% and 168 +/- 6% of
      baseline, respectively (n = 17). L-NAME attenuated the hyperemic response to
      hypoxia/reoxygenation in both ages (n = 11, in each age). Striatal NO production
      increased during hypoxia and reoxygenation in both ages, but the increase was
      significantly less in 7-d-old than in 14-d-old rats. The NO increase was
      associated with the increase in rCBF, and both were attenuated by L-NAME. We
      speculate that NO release during hypoxia/reoxygenation modulates rCBF. The
      immature young rat brain may have less capacity to activate NO production than
      the more developed brain.

PMID- 9621982
TI  - Protective effects of moderate hypothermia after neonatal hypoxia-ischemia: short
      and long-term outcome.
AB  - We have previously shown that mild hypothermia applied after hypoxia-ischemia in
      newborn piglets and rats reduces brain injury evaluated 3-7 d after the insult.
      The aim of the present study was to assess the neuroprotective efficacy of
      hypothermia with respect to short- (neuropathology) and long-term (neuropathology
      and sensorimotor function) outcome after hypoxia-ischemia in 7-d-old rats. One
      hundred fourteen animals from 13 litters survived either 1 or 6 wk after a
      hypoxic-ischemic insult. The animals were randomized to either 1) normothermic
      recovery for the whole 1- or 6-wk period or 2) cooling to a rectal temperature of
      32.0 degrees C for the first 6 h followed by normothermic recovery with the dam.
      Hypothermia offered a uniform protection of 27, 35, 28, and 25% in cerebral
      cortex, hippocampus, basal ganglia, and thalamus, respectively, in the 1-wk
      survivors (n = 32). The corresponding values for the 6-wk survivors (n = 61) were
      22, 28, 37, and 35%. There was a significant correlation between sensorimotor
      performance and infarct volume (r = 0.66; p < 0.001). However, the sensorimotor
      function was not significantly improved by hypothermia if all animals were
      included, but in female pups the total functional score was higher in the
      hypothermia group (150 +/- 35 versus 100 +/- 34, p < 0.0007) which corresponded
      to a marked (51%) reduction of the neuropathology score in this subgroup. This is
      the first neonatal study to show a long-term histopathologic protection of the
      brain after posthypoxic hypothermia.

PMID- 9621983
TI  - Cytokine response in cerebrospinal fluid after birth asphyxia.
AB  - Experimental studies suggest that cytokine-mediated inflammatory reactions are
      important in the cascade leading to hypoxic-ischemic brain injury. The purpose
      was to study the content of pro- and antiinflammatory cytokines in cerebrospinal
      fluid (CSF) of asphyxiated and control infants. Samples of CSF were obtained from
      20 infants who fulfilled the criteria of birth asphyxia and from seven newborn
      control subjects. The concentrations of IL-1beta, IL-8, IL-10, tumor necrosis
      factor (TNF)-alpha, and granulocyte/monocyte colony-stimulating factor (GM-CSF)
      were determined with ELISA and of IL-6 using a bioassay. The concentration of IL
      6 (pg/mL) was higher in asphyxiated (250, 35-543; median, interquartile range)
      than in control (0, 0-18) infants (p = 0.001). There was also a significant
      relationship between IL-6 and the degree of HIE, and between IL-6 and outcome. In
      addition, the content of IL-8 (pg/mL) was higher (p = 0.009) in the asphyxia
      group (170, 70-1440), than in the the control group (10, 0-30) and there was an
      association between IL-8 and degree of HIE. The levels of IL-10, TNF-alpha, GM
      CSF, and IL-1beta did not differ between groups. In conclusion, the
      proinflammatory cytokines IL-6 and IL-8 were markedly elevated in CSF of
      asphyxiated infants, and the intrathecal levels of these cytokines corresponded
      to the degree of HIE.

PMID- 9621984
TI  - Different meaning of CD38 molecule expression on CD4+ and CD8+ cells of children
      perinatally infected with human immunodeficiency virus type 1 infection surviving
      longer than five years.
AB  - We investigated the relationship between CD4+CD38+, CD4+HLA-DR+, CD8+CD38+, and
      CD8+HLA-DR+ cell proportions (HLA-DR = major histocompatibility complex class II)
      (determined by two-color immunofluorescence) and the clinical condition, IL-2 and
      IL-6 production, viral RNA copy numbers, and the eventual immunologic-virologic
      course in 25 children perinatally infected with HIV-1 surviving longer than 5 y
      [median age, 92 (range, 63-136) mo]. Twelve healthy age-matched children were
      studied as control subjects. HIV-1+ children had lower percentages and absolute
      numbers of CD4+CD38+, whereas the percentages of CD4+HLA-DR+ and the percentages
      and absolute numbers of CD8+CD38+ and CD8+HLA-DR+ cells were higher than that of
      control subjects. The absolute numbers of CD4+ and the percentages of CD4+CD38+,
      CD8+CD38+, and CD8+HLA-DR+ cells directly correlated, whereas the percentages of
      CD4+CD38+ and CD4+HLA-DR+ cells, the percentages of CD4+CD38+ and CD8+CD38+
      cells, the CD8+ cell absolute numbers, and the percentages of CD8+CD38+ cells did
      not. Severe manifestations and immunologic deterioration occurred in children
      with low CD4+CD38+ cell percentages, whereas virologic worsening was associated
      with low CD8+CD38+ and CD8+HLA-DR+ cell percentages. IL-2 production directly
      correlated with percentages and absolute numbers of CD4+CD38+ and CD8+CD38+
      cells. RNA copy numbers inversely correlated with CD4+CD38+, CD4+HLA-DR+,
      CD8+CD38+, and CD8+HLA-DR+ cell percentages. This suggests that CD38 molecule
      expression on both CD4+ and CD8+ cell subsets is a favorable marker in HIV-1+
      children. Perhaps CD8+CD38+ subsets are activated cells, whereas CD4+CD38+
      subsets are immature cells, possibly the host's attempt at CD4+ cell renewal.

PMID- 9621985
TI  - Monocyte chemoattractant protein-1 and interleukin-8 levels in urine and serum of
      patents with hemolytic uremic syndrome.
AB  - The epidemic form of the hemolytic uremic syndrome (HUS) in children is
      hallmarked by endothelial cell damage, most predominantly displayed by the
      glomerular capillaries. The influx of mononuclear (MO) and polymorphonuclear
      cells (PMNs) into the glomeruli may be an important event in the initiation,
      prolongation, and progression of glomerular endothelial cell damage in HUS
      patients. The molecular mechanisms for the recruitment of these leukocytes into
      the kidney are unclear, but monocyte chemoattractant protein-1 (MCP-1) and IL-8
      are suggested to be prime candidates. In this study, we analyzed the presence of
      both chemokines in 24-h urinary (n = 15) and serum (n = 14) samples of HUS
      children by specific ELISAs. Furthermore, kidney biopsies of three different HUS
      children were examined for MO and PMN cell infiltration by histochemical
      techniques and electron microscopy. Whereas the chemokines MCP-1 and IL-8 were
      present in only very limited amounts in urine of 17 normal control subjects,
      serial samples of HUS patients demonstrated significantly elevated levels of both
      chemokines. HUS children with anuria showed higher initial and maximum chemokine
      levels than their counterparts without anuria. A strong positive correlation was
      observed between urinary MCP-1 and IL-8 levels. Whereas initial serum IL-8 levels
      were significantly increased in HUS children, serum MCP-1 levels were only
      slightly elevated compared with serum MCP-1 in control children. No correlation
      was found between urinary and serum chemokine concentrations. Histologic and EM
      studies of HUS biopsy specimens clearly showed the presence of MOs and to a
      lesser extent of PMNs in the glomeruli. The present data suggest an important
      local role for MOs and PMNs in the process of glomerular endothelial-cell damage.
      The chemokines MCP-1 and IL-8 may possibly be implicated in the pathogenesis of
      HUS through the recruitment and activation of MOs and PMNs, respectively.

PMID- 9621986
TI  - The influence of meat on nonheme iron absorption in infants.
AB  - During weaning the infant has a high iron requirement, and highly available
      dietary iron is needed to ensure optimal iron status. Muscle tissue has been
      identified as an enhancer of nonheme iron absorption in adults, although the
      influence of meat on nonheme iron absorption in infants has not been previously
      reported. The effect of the addition of 25 g of meat (lean beef) on nonheme iron
      absorption from a home-prepared vegetable puree meal (80 g of vegetables) was
      investigated in infants in the present study. The meals did not differ in their
      contents of other known enhancers or inhibitors of nonheme iron absorption.
      Incorporation of stable isotopes of iron (57Fe and 58Fe) into red blood cells 14
      d after intake was used to measure iron absorption, using a cross-over design in
      eight healthy infants 43-49 wk of age. Nonheme iron absorption was significantly
      increased (p = 0.002) from the vegetable puree with added meat (geometric mean
      15.0%) compared with the pureed vegetables (geometric mean 9.9%). These results
      thus suggest that meat is also an enhancer of nonheme iron absorption in infants
      and that nonheme iron absorption from weaning foods can be increased by the
      addition of meat.

PMID- 9621987
TI  - Hematopoiesis in the liver and marrow of human fetuses at 5 to 16 weeks
      postconception: quantitative assessment of macrophage and neutrophil populations.
AB  - During human development, the liver and marrow both function as hematopoietic
      organs, but little is known about differences in the production of macrophages
      and neutrophils by these two organs. We used immunohistochemical stains to
      quantify the ratio of neutrophils to macrophages within the liver and the marrow
      of 16 fetuses from 5 to 16 wk postconception. At 5 wk the liver had a ratio of
      one granulocyte [myeloperoxidase (MPO)-positive cell] to every 9 +/- 5 (X +/- SD)
      macrophages (KP-1-positive cells). Between 5 and 16 wk, the granulocyte to
      macrophage ratio in the liver was constant, whereas it changed markedly in the
      marrow. Before 8 wk no MPO-positive or KP-1-positive cells were observed in
      bones. At 10 wk, bones still had no MPO-positive cells, but KP-1-positive cells
      were abundant. At 11-12 wk the granulocyte to macrophage ratio was 1 to 1 +/- 1,
      but by 13-16 wk it had increased to 8 +/- 3 MPO-positive cells to one KP-1
      positive cell. We hypothesized that at 13-16 wk the abundance of MPO-positive
      cells in the marrow and their scarcity in the liver was the result of production
      of granulocyte colony-stimulating factor (G-CSF) and its receptor (G-CSF-R) in
      the marrow and their absence in the liver. However, by reverse transcriptase-PCR
      mRNAs for G-CSF and G-CSF-R were positive in both organs at all gestations, and G
      CSF and G-CSF-R proteins (by immunohistochemistry) were also abundant in all
      liver and marrow specimens. We then hypothesized that progenitors in the fetal
      liver were intrinsically different from those in the marrow, and were unable to
      generate clones of neutrophils. However, progenitors from the liver produced
      neutrophils abundantly in culture. Thus, the explanation is likely related to as
      yet undescribed environmental differences between the fetal liver and marrow.

PMID- 9621988
TI  - The perinatal expression of aquaporin-2 and aquaporin-3 in developing kidney.
AB  - The kidney provides an important contribution to permit the fetus to successfully
      transition to an independent existence by production of urine with significantly
      different osmolality compared with plasma. Although recent work has uncovered
      many aspects of the maturation and regulation of the renal concentrating and
      diluting mechanism, understanding of how alterations in the expression of
      aquaporin (AQP) water channels contribute to the formation of urine in the
      perinatal period is incomplete. Here, we report that both AQP-2 and -3 are
      expressed during fetal life as early as embryonic d 18 in ureteric buds of rat
      kidneys, where each is localized to the apical and basolateral membranes of
      epithelial cells, respectively. Northern analyses demonstrate that the 1.9-kb AQP
      2 transcript is present in fetal and postnatal rat kidneys similar to that
      observed in adults. AQP-2 mRNA expression increases after d 3 of postnatal life.
      Immunoblotting reveals an increase in total kidney AQP-2 protein particularly
      with respect to its glycosylated form after postnatal d 3. AQP-3 protein also
      exhibits a similar alteration likely due to a similar increase in its
      glycosylation state. Both AQP-2 and AQP-3 display a distribution in the
      collecting ducts of human postnatal infants and adults identical to that
      exhibited in rat kidneys. These data show that both AQP-2 and -3 are present in
      collecting duct epithelia of fetal and postnatal kidneys. Thus, the reduced AVP
      responsiveness and decreased urinary concentrating ability of the kidney during
      the fetal and immediate postnatal period does not appear to be caused by lack of
      AQP-2 or AQP-3 proteins.

PMID- 9621989
TI  - Effects of fish oil and alpha-tocopherol in immunoglobulin A nephropathy in the
      rat.
AB  - Alpha-tocopherol and fish oil have been reported to modulate the progression of
      IgA nephropathy in animals and humans. Because fish oil has been reported to
      exacerbate renal disease in subtotal nephrectomized rats, we investigated the
      effects of fish oil, with and without alpha-tocopherol, on the course of IgA
      nephropathy. Experimental IgA nephropathy was induced in male Sprague-Dawley
      rats, weighing 170-200 g, by oral and i.v. immunization with bovine gamma
      globulin for 8 wk. IgA nephropathy was evidenced by hematuria, proteinuria, and
      IgA deposition in the mesangium. Standard rodent chow, containing 30 IU of alpha
      tocopherol/kg of diet, was given to the control and IgA nephropathy rats. Fish
      oil (20% wt/wt), stripped of alpha-tocopherol preservative, was given to control
      and a second group of IgA nephropathy rats. Alternatively, corn oil or fish oil
      was supplemented with alpha-tocopherol at 100 IU/kg of diet and given to the
      third and fourth groups of IgA nephropathy rats. All animals were killed at 8 wk.
      Urinary protein excretion, plasma and kidney alpha-tocopherol concentrations, as
      well as glomerular planar area, and kidney transforming growth factor-beta1 mRNA
      were analyzed. As determined by reductions in proteinuria, glomerular planar
      area, and TGF-beta1 mRNA, fish oil with alpha-tocopherol ameliorated the renal
      injury induced by bovine gamma-globulin, whereas fish oil without alpha
      tocopherol did not. Our findings support the importance of alpha-tocopherol, more
      so than fish oil, in mitigating the injury and promoting repair in experimental
      IgA nephropathy.

PMID- 9621990
TI  - Serum angiogenin levels in children and adolescents with insulin-dependent
      diabetes mellitus.
AB  - Microangiopathy, one of the most important complications of diabetes mellitus in
      humans, is associated with increased angiogenic response and proliferative
      lesions in various organs. Angiogenin, a polypeptide with a molecular size of 14
      kD, is a potent inducer of vascular growth. This study aimed at investigating
      whether serum angiogenin levels are elevated in children and adolescents
      (youngsters) with insulin-dependent diabetes mellitus and whether angiogenin
      levels are affected by duration and metabolic control of the disease. It is
      assumed that angiogenin levels reflect the increased angiogenesis associated with
      microangiopathy, whether clinically evident or not. Forty diabetic youngsters
      were compared with 30 healthy control subjects (mean age +/- SD, 14.3 +/- 3.6 y
      and 13.8 +/- 3.6 y, respectively). The patients' disease duration and
      glycosylated Hb were (mean +/- SD) 6.2 +/- 3.8 y and 9.6 +/- 1.8%, respectively.
      Angiogenin (ng/mL) was measured in serum samples by an enzyme immunoassay and was
      found to be significantly higher (mean +/- SE) in patients (353.3 +/- 20.0) than
      in control subjects (244.7 +/- 9.6) (p = 0.0002). Levels did not vary with age,
      but were significantly higher in females compared with male subjects (p = 0.01).
      In the diabetic youngsters no significant differences were noticed with respect
      to duration or metabolic control of the disease. In conclusion, serum angiogenin
      levels were found to be increased among diabetic youngsters, irrespective of the
      duration and metabolic control of the disease, as well as in female subjects,
      with or without diabetes.

PMID- 9621991
TI  - Antenatal dexamethasone treatment decreases plasma catecholamine levels in
      preterm infants.
AB  - Antenatal corticosteroid therapy (ACT) has many beneficial effects on preterm
      infants. The cellular mechanisms of action of ACT include beta-adrenergic
      receptor-mediated cAMP generation. This study investigated the effects of ACT on
      sympathoadrenal mechanisms during immediate postnatal adaptation of preterm
      infants. Plasma epinephrine, norepinephrine, 3,4-dihydroxyphenylglycol, and cAMP
      were measured within 12 h after birth in 103 preterm infants (gestational age 24
      36 wk), who were divided into two groups (non-ACT and ACT group) according to
      whether the mother had received dexamethasone treatment. Infants in the ACT group
      had significantly lower concentrations of plasma catecholamines than infants in
      the non-ACT group; plasma epinephrine was 38% lower, and plasma norepinephrine
      was 20-40% lower in the ACT group, depending on gestational age (r = -0.37 in the
      non-ACT group and r = -0.28 in the ACT group, p < 0.05). Plasma cAMP
      concentrations were similar in the two groups. Antihypertensive treatment of the
      mother was associated with low plasma cAMP (p < 0.001), whereas tocolytic
      treatment was associated with high plasma cAMP (p = 0.001) of the infant. The
      results indicate that ACT attenuates the birth-related increase in plasma
      catecholamines. Still, plasma cAMP levels remain high, which suggests enhanced
      beta-adrenoceptor signaling after ACT.

PMID- 9621992
TI  - Prediction factors in the determination of final height in subjects born small
      for gestational age.
AB  - The aim of this study was to identify factors predictive of individual final
      height (FH) in subjects born small for gestational age (SGA). All full-term
      singleton subjects born SGA (birth weight and/or length <3rd percentile) during
      the period 1971-1978, matched with appropriate birth weight for gestational age
      (AGA) subjects (birth weight between 25th and 75th percentile) were followed from
      birth to FH and evaluated before puberty at a mean age +/- SD of 6.1 +/- 0.7 y
      and after puberty at a mean age of 20.8 +/- 2.0 y (subjects born SGA, n = 213;
      born AGA, n = 272). When adjusted for target height, a significant deficit in
      final height (p < 0.0001) was found in SGA as compared with AGA subjects for both
      male subjects (-3.99 cm with 95% confidence interval from -5.6 to -2.4) and
      female subjects (-3.64 cm with 95% confidence interval from -5.0 to -2.3), with
      13.6% of subjects in the SGA population presenting short final stature. In a
      multiple regression analysis, target height and studied group (SGA or AGA) were
      found to be the strongest predictors of individual FH (p < 0.0001, r2 = 0.35 for
      male subjects, p < 0.0001, r = 0.40 for female subjects). For SGA subjects and
      according to a multiple stepwise linear regression model, 31% of the variability
      of individual FH [SD score (SDS)] and 58% of the variability of individual height
      gain SDS could be explained at birth from mother's height, father's height, and
      birth length SDS. No other variables were found to be predictive such as sex,
      gestational age (from 37 to 42 wk), birth weight SDS, ponderal index at birth, or
      risk factors during pregnancy associated with intrauterine growth retardation
      such as pregnancy-induced hypertension, smoking, or a history of SGA in
      offspring. Although a significant increase of body mass index SDS was documented
      before and after puberty in SGA subjects, puberty was not found to have any
      influence on growth outcome.

PMID- 9621993
TI  - Assembly of tropomyosin isoforms into the cytoskeleton of avian muscle cells.
AB  - Tropomyosin (TM) is a component of microfilaments of most eukaryotic cells. In
      striated muscle, TM helps confer calcium sensitivity to the actin-myosin
      interaction. TM is a fibrillar, self-associating protein that binds to the
      extended actin filament system. We hypothesized that these structural features
      would permit TM to undergo assembly into the cytoskeleton during translation, or
      cotranslational assembly. Pulse-chase experiments with [35S]methionine and pulse
      experiments with [3H]puromycin followed by extraction and immunoprecipitation of
      TM were performed to examine the mechanism of assembly of TM into the
      cytoskeleton in cultured avian muscle cells. Pulse-chase experiments provide
      kinetic evidence for cotranslational assembly of TM in skeletal and cardiac
      muscle. Demonstration of a large majority of completed TM on purified skeletal
      muscle microfilaments after a short labeling period confirms that these kinetic
      data are not related to trapping of TM within the actin network of the
      cytoskeleton. Nascent TM peptides are demonstrated on the cytoskeleton of muscle
      cells after a short metabolic pulse followed by puromycin treatment to release
      nascent peptides from ribosomes or after labeling with [3H]puromycin. Nascent
      chain localization to the cytoskeleton independent of ribosomal attachment
      further confirms the high degree of cotranslational assembly of this protein. The
      extent of cotranslational assembly is similar before and after the formation of
      significant myofibril in myotubes, suggesting that cotranslational assembly of TM
      is active during contractile apparatus assembly in muscle differentiation. This
      is the first report where assembly mechanism has been predicted to be
      cotranslational based upon structural features of a cytoskeletal protein.

PMID- 9621994
TI  - Probing the order within neonatal heart rate variability.
AB  - The mechanism by which heart rate variability (HRV) changes during neonatal
      illness is not known. One possibility is that reduced HRV is merely a diminished
      or scaled-down version of normal. Another possibility is that there is a
      fundamental change in the mechanism underlying HRV, resulting in a change in the
      ordering of RR intervals. We investigated the nature and extents of order in RR
      interval time series from 25 Neonatal Intensive Care Unit patients with a
      spectrum of clinical illness severity and HRV. We measured predictability
      (deviation of predicted intervals from observed), and regularity (measured as
      approximate entropy) of RR interval time series showing different degrees of HRV.
      In RR interval time series where the effects of scaling were removed, we found 1)
      records showing normal HRV had more order than those showing low HRV; 2) the
      nature of the order was more like that of a periodic process with frequencies
      over a large range (time series whose log-log power spectrum had a 1/f
      distribution) than that of chaotic one (logistic map); and 3) the nature of order
      did not change greatly as HRV fell. We conclude that neonatal RR interval time
      series are ordered by periodic processes with frequencies over a large range, and
      that the extent of order is less during illness when HRV is low.

PMID- 9621995
TI  - Quantitative bronchoscopic assessment of airway collapsibility in newborn lamb
      tracheae.
AB  - To date, quantitative studies of the inherent characteristics of the developing
      airway wall have required excision of an airway segment or surgical creation of
      an isolated segment. We hypothesized that airway wall characteristics, at various
      collapsing pressures, and attendant changes in stiffness after smooth muscle
      stimulation could be quantitated bronchoscopically from airway pressure-area
      relationships. Neonatal lamb tracheal segments (n = 12) were suspended over
      hollow mounts, in a buffer-filled chamber, and subjected to a range (0 to -4.0
      kPa) of pressures to determine wall stiffness under collapsing forces before and
      after stimulation of the trachealis with methacholine. Luminal images were
      recorded through a 3.6-mm flexible bronchoscope under the same conditions,
      subsequently corrected for distortion, and a cross-sectional area was
      quantitated. Both pressure-volume and pressure-area relationships detected
      significant changes in airway wall stiffness after methacholine administration (p
      < 0.002), and the magnitude of change was similar between methods. These data
      suggest that quantitative flexible bronchoscopy can be used clinically in the
      intact airway to assess wall stiffness.

PMID- 9621996
TI  - Regional hemodynamic responses to visual stimulation in awake infants.
AB  - This study presents the first measurements using near infrared spectroscopy of
      changes in regional hemodynamics as a response to a visual stimulus in awake
      infants. Ten infants aged 3 d to 14 wk viewed a checkerboard with a 5-Hz pattern
      reversal. The emitter and detector (optodes) of a near infrared spectrophotometer
      were placed over the occipital region of the head. Changes in concentration of
      oxy- and deoxyhemoglobin (Hbo2 and Hb) were measured and compared during 10-s
      epochs of stimulus on and off. A control group of 10 infants aged 18 d to 13 wk
      were examined with the same setup, but with the optodes over the frontoparietal
      region. In the test group the total hemoglobin concentration (Hbo2 + Hb)
      increased while the stimulus was on by a mean (+/-SD) of 2.51 (+/-1.48) micromol
      x L(-1). Nine out of 10 infants showed an Hbo2 increase, and 9 out of 10 an Hb
      increase related to the stimulus. There was no significant change in any of these
      parameters in the control group. The results imply that there is increased
      cerebral blood flow due to stimulation that is specific to the visual cortex and
      that infants, unlike adults, show increased cerebral oxygen utilization during
      activation that outstrips this hemodynamic effect. The study demonstrates that
      near infrared spectroscopy can be used as a practical and noninvasive method of
      measuring visual functional activation and its hemodynamic correlates in the
      awake infant.

PMID- 9621997
TI  - Apolipoprotein E genotype in sporadic early- and late-onset Alzheimer's disease.
AB  - The 84 isoform of apolipoprotein E (ApoE) has been proposed as a risk factor for
      Alzheimer's disease (AD), while the possible role of the epsilon2 allele in AD is
      controversial. We have studied the ApoE genotype in 38 patients with early-onset
      AD (EOAD) and in 43 patients with late-onset AD (LOAD). In the EOAD group we
      observed a significant increase of epsilon4 allele frequency as compared with
      normal controls, while there was a more than 3-fold decrease of epsilon2 allele
      frequency that did not reach statistical significance. In the LOAD group we found
      a highly significant increase of epsilon4 allele frequency as compared with
      normal controls, while there was a significant decrease of epsilon2 allele
      frequency. In both the EOAD and LOAD groups, no significant difference was
      observed between epsilon4 carriers and epsilon4 noncarriers as for age at disease
      onset, disease duration, and Mini-Mental State score at observation. However, in
      both EOAD and LOAD groups a statistical trend towards a longer disease duration
      was observed in epsilon4 carriers. In both the EOAD and LOAD groups, disease
      severity was compared in epsilon4 carriers versus epsilon4 noncarriers by means
      of analyses of covariance, with disease duration as covariate. No significant
      difference between epsilon4 carriers and epsilon4 noncarriers was observed in
      both EOAD and LOAD. The results of the present study confirm that epsilon4 allele
      seems to be associated with an increased risk for sporadic AD, while the
      significant decrease of epsilon2 allele frequency in the LOAD group supports the
      hypothesis of a possible protective role of epsilon2 allele in AD.

PMID- 9621998
TI  - Increased plasma concentration of serum amyloid P component in centenarians with
      impaired cognitive performance.
AB  - Serum amyloid P component (SAP) binds to all amyloid fibrils including those in
      the plaques and tangles of Alzheimer patients. To investigate whether the plasma
      SAP concentration correlated to cognitive impairment, we measured SAP levels in
      blood samples from 41 centenarians and compared these to the cognitive
      performance evaluated by Mini Mental State Examination (MMSE). We observed a
      significantly (p < 0.001) increased SAP concentration (48.3+/-16.9 microg/ml;
      mean +/- SD) in the centenarians compared to gender-matched controls (32.8+/-11.4
      microg/ml). Six severely demented centenarians had an even higher SAP
      concentration (60.2 microg/ml), while the subgroup of cognitive intact
      centenarians (MMSE score >24) showed a normal SAP concentration (38.4+/-9.3
      microg/ml). No dehydration or hepatic dysfunction was demonstrable in the
      centenarians. We conclude that the centenarians with impaired cognitive
      performance had significantly increased plasma concentrations of SAP, while the
      values for cognitive intact centenarians were within the normal range.

PMID- 9621999
TI  - Serial position effects in dementia of the Alzheimer type.
AB  - BACKGROUND: The aim of the present study was to analyse serial position effects
      for immediate and delayed free recall in patients with dementia of the Alzheimer
      type and controls. EXPERIMENT 1: 44 patients with dementia of the Alzheimer-type
      and 24 non-demented controls were asked for immediate and delayed free recall of
      12 schematic drawings of common objects presented at the rate of 10 s/picture.
      Steep primacy effects were obtained at all delays in controls. By contrast,
      primacy effects were significantly impaired in patients with dementia at all
      delays of recall. Small immediate and delayed recall recency effects were found
      in both, patients and controls. EXPERIMENT 2: 19 patients with dementia of the
      Alzheimer type and 21 controls were asked for immediate and delayed free picture
      recall with presentation rates of 10, 5 and 1 s/picture. Again, primacy effects
      were significantly impaired in demented patients versus controls. With shorter
      presentation times, immediate recall recency effects were more pronounced than
      with longer presentation times, and no delayed recall recency effects were found.
      CONCLUSIONS: Primacy effect is impaired for immediate and delayed recall in
      dementia of the Alzheimer type. By contrast, immediate recall recency effect and
      possibly also long-term recency effect are preserved. The loss of the primacy
      effect contributes to the impairment of episodic memory in dementia of the
      Alzheimer type. Therefore further research is warranted into pharmacological and
      psychological interventions that might re-establish the primacy effect. Possibly,
      the orientation of demented patients might be improved by psychological
      techniques that rely on long-term recency effect.

PMID- 9622000
TI  - Lack of association between an intronic polymorphism in the presenilin-1 gene and
      sporadic late-onset Alzheimer disease in Polish patients.
AB  - The apolipoprotein E (APOE) gene has in many studies been identified as a
      susceptibility factor in Alzheimer's disease (AD). The APOE association is rather
      strong, but other not yet identified genetic factors are assumed to be involved
      in the pathogenesis of AD. Recently an association between an intronic
      polymorphism in presenilin-1 (PS-1) gene and late-onset AD was claimed. In order
      to confirm this observation we studied a sample of Polish patients with sporadic
      AD. However, our results did not confirm the existence of an association between
      the intronic polymorphism in the PS-1 gene and late-onset AD.

PMID- 9622001
TI  - Assessment of the pathological stages of Alzheimer's disease in thin paraffin
      sections: a comparative study.
AB  - The staging method proposed by Braak and Braak allows the objective and reliable
      assessment of Alzheimer-related neurofibrillary pathology. Originally the method
      was designed for 100-microm thick sections. However, the use of thick sections
      proved to present difficulties in a routine neuropathology laboratory. In order
      to adapt the staging method for thin paraffin-embedded sections, we performed an
      inter- and intrarater study analysing the reliability of the staging method in
      thin sections. Statistical analysis of the data provided by six independent
      examiners in two rating sessions reveal kappa values of 0.6-0.8 for both the
      interrater and the intrarater reliability. The average rate of mistake of the
      examiners was rarely bigger than a half stage. We conclude that the adapted
      staging method in thin sections is strongly reliable and we recommend it for
      staging purposes in institutions where the preparation of thick sections would be
      difficult.

PMID- 9622002
TI  - The expression of presenilin-1 mRNA in skin fibroblasts from Alzheimer's disease.
AB  - The presenilin-1 (PS-1) gene was recently identified as one of the causative
      genes in the early onset of familial Alzheimer's disease (AD). Analysis of the PS
      1 gene is thought to be useful in clarifying the pathogenesis of AD. However,
      there have been few reports about the expression of the PS-1 gene in AD. In this
      study, we analyzed the expression of PS-1 mRNA in cultured skin fibroblasts taken
      from living patients with AD by Northern blot analysis. The subjects consisted of
      18 cases with AD and 10 cases of neurological patients without dementia (CTL). We
      found that the PS-1 mRNA levels in AD were significantly higher than those in CTL
      (p < 0.01). Moreover, we found that the PS-1 mRNA level increases in the early
      stages of AD and tends to decrease in the advanced stages. These findings suggest
      that high levels of PS-1 mRNA may play an important role in developing AD.

PMID- 9622003
TI  - Decreased immunosuppressive effect of cortisol on natural killer cytotoxic
      activity in senile dementia of the Alzheimer type.
AB  - Former studies have indicated alterations of the cytotoxic activity of natural
      killer (NK) cells in senile dementia of the Alzheimer type (SDAT). These changes
      may be related to the increased reactivity of NK cells with cytokines, even if an
      impairment of the immunosuppressive effect of glucocorticoids cannot be excluded.
      In the present study we have demonstrated a lower immunosuppressive effect of
      cortisol on NK cytolytic function in patients with SDAT than in healthy elders
      and in patients with dementia of multi-infarct origin (MID). This suppression is
      completely lacking when cortisol is employed at low concentrations (10(-7) M) and
      is significantly reduced after incubation at physiological (10(-6) M; p < 0.001)
      and supraphysiological concentrations (10(-5) M; p < 0.001). The addition of IL-2
      (50 and 100 IU/ml/cells) significantly antagonizes the effects of cortisol in
      SDAT, whereas the cortisol-dependent immunosuppression is partially maintained in
      healthy elders and in patients with MID. Our data indicate that the defect of the
      immunosuppressive effect of cortisol may play a role in NK dysregulation in SDAT,
      contributing to the cytokine-mediated NK overactivity in this disease.

PMID- 9622004
TI  - Determinants of global clinical change assessment in patients with early
      Alzheimer's disease.
AB  - Global clinical impression (GCI) of change is assumed to integrate aspects of
      both cognitive and noncognitive functioning. We evaluated 140 consecutive
      patients with probable (n = 90) and possible (n = 50) early Alzheimer's disease
      at baseline and after 6 months with measurements of global cognitive function
      (CAMCOG), behavior, activities of daily living, and burden of the caregiver.
      After 6 months, both the clinician (GCI-clin) and the caregiver (GCI-care) rated
      clinical change on a 3-point scale (worse, no change, improved). Data were
      analyzed with multiple polychotomous logistic regression, adjusted for age and
      sex. Change in global cognitive function and GCI-care were significantly and
      independently related to GCI-clin, while changes in activities of daily living
      and in behavior were significantly and independently associated with GCI-care.
      The findings suggest a double dissociation. Change in cognition appears to be the
      major determinant of the clinician's global impression but not change in
      behavioral and functional parameters, while global impression of the caregiver is
      primarily based on change in behavioral and functional measures but not on change
      in cognition.

PMID- 9622005
TI  - Differentiating Alzheimer's disease and frontotemporal dementia: receiver
      operator characteristic curve analysis of four rating scales.
AB  - Alzheimer's disease and frontotemporal dementia are two of the most common types
      of degenerative dementia. In conjunction with a complete neuropsychiatric
      examination, the Executive Interview, Mini-Mental State Exam, Alzheimer's Disease
      Scale, Pick's Disease Scale and the Informant-Based Questionnaire have been used
      to distinguish between these two disorders on clinical grounds. In a review of
      two studies, scores from these rating scales are subjected to receiver operator
      characteristic curve analysis to determine the cut-off value for each scale which
      yields the highest sensitivity and specificity with regard to differentiating
      between Alzheimer's disease and frontotemporal dementia. Finally, the Informant
      Based Questionnaire is discussed and compared to each rating scale to demonstrate
      the important features and limitations of each.

PMID- 9622006
TI  - Vascular risks and incident dementia: results from a cohort study of the very
      old.
AB  - The contribution of vascular pathology to the manifestation of dementia and the
      importance of vascular risk to measures of cognitive function is being
      increasingly recognized. In particular, confirmation of this risk points towards
      approaches for prevention in large sections of the population. Information on
      determinants of incident dementia is increasing, but still relatively few studies
      of risk have been based on incident cases of dementia in very elderly
      populations. In this study based on incident cases of dementia in a population
      aged 75 and over, vascular risks were obtained from informants of the respondents
      with incident dementia. When compared with controls the factors associated with
      incident dementia were history of heart attack (odds ratio 2.9), transient
      ischaemic attacks (4.8), cerebrovascular accidents (3.4), family history of first
      degree relatives with dementia (4.0), and occupational exposure to vibrating
      instruments (1.4). If only Alzheimer's disease, clinically diagnosed, was
      included, diabetes (1.4) and a history of dementia in first-degree relatives
      (6.6) emerged. Thus, vascular risk continues to be of importance in the oldest
      age groups.

PMID- 9622007
TI  - Sequential genesis and determination of cone and rod photoreceptors in Xenopus.
AB  - In this study, we addressed the temporal sequence of photoreceptor fate
      determination in Xenopus laevis by examining a number of key events during early
      cone and rod development. We compared the relative timing and spatial pattern of
      cone and rod specification using a number of cell type-specific markers,
      including probes to a long wavelength-sensitive opsin which is expressed by the
      major cone subtype. Our results show that cones are initially more numerous, and
      can arise in less mature regions of the retina than rods, although both types of
      photoreceptors begin to express their respective opsins at about the same time.
      We applied these markers to an assay of cellular determination to identify the
      stages of embryonic development at which the earliest photoreceptor fates are
      induced in vivo. The relative birth order of the major cone and rod subtypes was
      revealed by simultaneous labeling with markers of cell proliferation and terminal
      differentiation. Although there is much temporal overlap between the periods of
      cone and rod genesis and determination in Xenopus, we could discern that the
      earliest cones are both born and determined before the first rods. Thus, even in
      the rapidly developing retina of Xenopus, photoreceptors achieve their identities
      in a sequential fashion, suggesting that the inductive cues which determine
      specific photoreceptor fates may also arise sequentially during development.

PMID- 9622008
TI  - Role for calcium from the sarcoplasmic reticulum in coupling muscle activity to
      nicotinic acetylcholine receptor gene expression in rat.
AB  - Neurally evoked muscle electrical activity suppresses nicotinic acetylcholine
      receptor (nAChR) gene expression in extrajunctional domains of adult muscle
      fibers. It has been proposed that this regulation is mediated by calcium influx
      through voltage-dependent L-type calcium channels but bypasses the sarcoplasmic
      reticulum in chick and mouse C2C12 cells. Here we report that in rat muscle
      calcium influx through L-type calcium channels preferentially reduced nAChR
      epsilon-subunit RNA via a post-transcriptional mechanism. In contrast, calcium
      release from the sarcoplasmic reticulum (SR) suppressed nAChR subunit RNA levels
      as a result of decreasing nAChR subunit promoter activity. Finally, we show that
      this decreased promoter activity is mediated through the same DNA sequences that
      control activity-dependent gene expression. Therefore, we propose that in rat
      muscle, calcium release from the SR participates in coupling muscle
      depolarization to nAChR gene expression.

PMID- 9622009
TI  - Level of p75 receptor expression in sensory ganglia is modulated by NGF level in
      the target tissue.
AB  - Neurotrophins play an essential role in sensory development by providing trophic
      support to neurons that innervate peripheral targets. Nerve growth factor (NGF),
      neurotrophin-3, neurotrophin-4, and brain-derived neurotrophin exert their
      survival effect by binding to two transmembrane receptor types: trk receptors,
      which exhibit binding specificity, and the p75NTR receptor, which binds all
      neurotrophins. To determine how target-derived neurotrophins affect sensory
      neuron development and function, we used transgenic mice that overexpress NGF in
      the skin to examine the impact of NGF overexpression on receptor expression.
      Previous studies of trk expression in trigeminal ganglia of adult NGF transgenics
      showed that the percentage of trkA neurons doubled and their number increased
      fivefold. The present study focused on the p75 receptor and shows that the
      percentage of neurons expressing p75NTR also increase in NGF ganglia, but only by
      10%. This increase did not encompass the small, BS-IB-4 isolectin-positive cells
      as they remained p75 negative in transgenic ganglia. Interestingly, levels of
      trkA protein were not increased on a per-cell level, whereas levels of p75NTR
      increased nearly threefold. These results show that in sensory systems, target
      derived NGF modulates the level of p75NTR receptor expression, and in so doing,
      may act to regulate the formation of functional receptor complexes and subsequent
      trophic action.

PMID- 9622010
TI  - Postembryonic neurogenesis in the procerebrum of the terrestrial snail, Helix
      lucorum L.
AB  - Neuronogenesis during posthatching development of the procerebrum of the
      terrestrial snail Helix lucorum was analyzed using bromodeoxyuridine
      immunohistochemistry to label proliferating cells. Comparison of the distribution
      of labeled cells in a series of animals which differed in age at the time of
      incubation with bromodeoxyuridine, in survival time after incubation, and in age
      at sacrifice reveals a clear pattern and developmental sequence in neuron origin.
      First, the proliferating cells are located only at the apical portion of the
      procerebrum. Second, cells which are produced at any particular age remain, for
      the most part, confined to a single layer in the procerebrum. Third, as
      development proceeds, each layer of previously produced neurons is displaced
      toward the basal part of the procerebrum by the production of additional neurons.
      Our results suggest that the vast majority of the neurons (probably about 70-80%)
      of the snail procerebrum are produced during the first 1-2 months of posthatching
      development.

PMID- 9622011
TI  - Basic FGF-responsive telencephalic precursor cells express functional GABA(A)
      receptor/Cl-channels in vitro.
AB  - We have previously described the expression of specific gamma-aminobutyric acid
      (GABA)A receptor subunits and their transcripts in the cortical neuroepithelium
      (Ma and Barker, 1995, 1998). However, it is not clear whether neural precursor
      cells exposed to basic fibroblast growth factor (bFGF) in vitro reproduce the
      biological properties of neuroepithelial cells in vivo within the embryonic
      ventricular zone. In the present study, neural precursor cells were isolated from
      the telencephalic neuroepithelium of embryonic day 13-13.5 rats and exposed to
      bFGF in serum-free medium. Basic FGF-responsive cells were capable of dividing
      and differentiating into neurons and astrocytes. The rapidly dividing cells
      formed multicellular spheres and then a rosette-like formation in which a
      majority of cells expressed GABA(A) receptor alpha4, beta1, or gamma1 subunit
      proteins. We found in perforated patch-clamp recordings that GABA depolarized
      bromodeoxyundine (BrdU)+ precursor cells, and under voltage-clamp induced a
      bicuculline-sensitive current that reversed at the Cl- equilibrium potential.
      GABA also increased cytoplasmic Ca2+ in a significant number of BrdU+ cells that
      was blocked by bicuculline. The bicuculline sensitivity of these pharmacological
      effects implicates GABA(A) receptor/Cl- channels, since bicuculline is a
      competitive GABA(A) antagonist at these channels in well-differentiated cells. It
      is possible that the three GABA(A) receptor subunits (alpha4, beta1, and gamma1)
      found in precursor cells form the Cl- channels detected electrophysiologically.
      The functional GABA(A) receptor/Cl- channels and associated regulation of their
      cytoplasmic Ca2+ levels via bicuculline-sensitive mechanisms may play significant
      roles in the regulation of neural cell proliferation in this model
      neuroepithelium.

PMID- 9622012
TI  - Distribution of phosphorylated GAP-43 (neuromodulin) in growth cones directly
      reflects growth cone behavior.
AB  - Phosphorylation of GAP-43 (neuromodulin) by protein kinase C (PKC) occurs at a
      single site, serine41. In vivo, phosphorylation is induced after initiation of
      axonogenesis and is confined to distal axons and growth cones. Within individual
      growth cones, phosphorylation is nonuniformly distributed. Here, we have used
      high-resolution video-enhanced microscopy of cultured dorsal root ganglia neurons
      together with immunocytochemistry with a monoclonal antibody that recognizes PKC
      phosphorylated GAP-43 to correlate the distribution of phosphorylated GAP-43 with
      growth cone behavior. In "quiescent," nontranslocating growth cones,
      phosphorylated GAP-43 was confined to the proximal neurite and the central
      organelle-rich region, and was low in organelle-poor lamellae. However, levels in
      lamellae were elevated when they became motile. Conversely, levels of
      phosphorylated GAP-43 were low in either lamellae that were actively retracting
      or in the central organelle-rich region and proximal neurite of growth cones that
      had totally collapsed. The results suggest a mechanism whereby phosphorylation of
      GAP-43 by PKC, potentially in response to extracellular signals, could direct the
      functional behavior of the growth cone.

PMID- 9622013
TI  - Programmed cell death of an identified motoneuron in vitro: temporal requirements
      for steroid exposure and protein synthesis.
AB  - Ecdysteroid hormones trigger the programmed cell death (PCD) of a segmental
      subset of accessory planta retractor (APR) motoneurons at pupation in the moth,
      Manduca sexta. APRs from abdominal segment four [APR (4)s] survive through the
      pupal stage, whereas homologous APR(6)s die 24-48 h after pupal ecdysis (PE) (the
      shedding of the larval cuticle), in response to the prepupal peak of
      ecdysteroids. Following retrograde labeling with the vital fluorescent dye, DiI,
      the morphology of APR(4)s and APR(6)s in vivo was examined at PE and 24-48 h
      later. During this period, APR(4) somata remained large and ovoid while APR(6)s
      somata became shrunken and rounded. Similar phenotypes were observed when DiI
      labeled APRs were cultured at PE and examined 24 h to 1 week later. During
      initial shrinkage and rounding of APR(6)s, the plasma membrane remained intact
      but DNA condensation occurred and mitochondrial activity was lost. The
      requirements for ecdysteroids and new protein synthesis for APR(6) death were
      tested by culturing cells with ecdysteroids and cycloheximide (CHX). When
      cultured at PE, the death of APR(6)s was independent of further exposure to
      ecdysteroids and could not be blocked by CHX. In contrast, APR(6)s cultured 24 h
      earlier required additional exposure to ecdysteroids to die and their death was
      inhibited by CHX. Thus, the final 24 h of larval life represents an important
      transition period in the commitment of APR(6)s to undergo PCD, and is of interest
      for pursuing underlying mechanisms of steroid-induced PCD.

PMID- 9622014
TI  - Distribution of androgen receptor-immunoreactive cells in the quail forebrain and
      their relationship with aromatase immunoreactivity.
AB  - The distribution of androgen receptor-like immunoreactive (AR-ir) cells in the
      quail brain was analyzed by immunocytochemistry with the use of the affinity
      purified antibody PG-21-19A raised against a synthetic peptide representing the
      first 21 N-terminal amino acids of the rat and human AR. This antibody is known
      to bind to the receptor in the absence as well as in the presence of endogenous
      ligands, and it was therefore expected that a more complete and accurate
      characterization of AR-ir cells would be obtained in comparison with previous
      studies using an antibody that preferentially recognizes the occupied receptor.
      Selected sections were double labeled for aromatase (ARO) by a technique that
      uses alkaline phosphatase as the reporter enzyme and Fast blue as the chromogen.
      AR-ir material was detected in the nucleus of cells located in a variety of brain
      areas in the preoptic region and the hypothalamus including the medial preoptic
      (POM), the supraoptic, the paraventricular (PVN), and the ventromedial (VMN)
      nuclei, but also in the tuberculum olfactorium, the nucleus accumbens/ventral
      striatum, the nucleus taeniae, the tuberal hypothalamus, the substantia grisea
      centralis (GCt), and the locus ceruleus. Cells exhibiting a dense AR-ir label
      were also detected in the nucleus intercollicularis. Preincubation of the primary
      antibody with an excess of the synthetic peptide used for immunization completely
      eliminated this nuclear staining. A significant number of AR-ir cells in the POM,
      VMN, PVN, and tuberal hypothalamus also contained ARO-ir material in their
      cytoplasm. These data confirm and extend previous studies localizing AR in the
      avian brain, and raise questions about the possible regulation by androgens of
      the metabolizing enzyme aromatase.

PMID- 9622015
TI  - Isolation and identification of a second diuretic hormone from Tenebrio molitor.
AB  - A diuretic hormone (DH) of unusual structure was isolated from extracts of heads
      of Tenebrio molitor. The hormone is a 47 amino acid peptide, Mr = 5,029.9, with
      the sequence AGALGESGASLSIVNSLDVLRNRLLLEIARKKAKEGANRNRQILLSL. This peptide
      increases cyclic AMP production in Malpighian tubules of T. molitor. We recently
      identified a smaller DH from T. molitor with 37 amino acids; these peptides have
      only 15 identical amino acids when aligned to maximize similarity to other
      members of the insect DH family. This family has sequence similarity to the
      corticotropin-releasing factor superfamily of vertebrate peptides.

PMID- 9622016
TI  - Biological activity of structural analogs and effect of oil as a carrier of
      trypsin modulating oostatic factor of the gray fleshfly Neobellieria bullata.
AB  - The trypsin modulating oostatic factor from the gray fleshfly Neobellieria
      bullata (Neb-TMOF) is released from the ovary at the end of vitellogenesis and
      inhibits trypsin biosynthesis in the midgut. This inhibition indirectly results
      in an arrest of oocyte growth. Additional experiments with N. bullata were
      performed to characterize its trypsin modulating and oostatic properties in more
      detail. After suspending the peptide in wheat germ oil, the threshold dose for
      oostatic activity was lowered one thousand times (2.10(-5) in oil versus 2.10(-2)
      pmoles per fly in Ringer). By use of the Neobellieria trypsin biosynthesis assay,
      17 analogs of the hexapeptide were tested for inhibitory activity. The following
      structural elements were demonstrated to be critical for biological activity: the
      alcohol function at position 3 (Thr residue); a positively charged basic group at
      the C terminus (His residue); and the Asn side chain at positions 1 and 4.

PMID- 9622017
TI  - Purification and cardiovascular activity of [Met1, Met5]-bradykinin from the
      plasma of a sturgeon (Acipenseriformes).
AB  - The sturgeons (Order Acipenseriformes) are extant representatives of a group of
      primitive Actinopterygian (ray-finned) fish that probably shared a common
      ancestor with present-day teleosts. Incubation of heat-denatured plasma from a
      sturgeon (a hybrid of the shovelnosed sturgeon Scaphirhynchus platorynchus and
      the pallid sturgeon Scaphirhynchus albus) with either trypsin or porcine
      pancreatic kallikrein generated bradykinin-like immunoreactivity. The primary
      structure of sturgeon bradykinin was established as Met-Pro-Pro-Gly-Met-Ser-Pro
      Phe-Arg. This amino acid sequence contains two amino acid substitutions (Arg1 -->
      Met and Phe5 --> Met) compared with mammalian bradykinin. Bolus injections of
      synthetic sturgeon bradykinin in doses as low as 1 pmol/kg into the dorsal aorta
      of unanesthetized sturgeon resulted in an immediate and significant fall in
      arterial blood pressure with a maximum depressor response at 300 pmol/kg. Thus,
      the cardiovascular response of the sturgeon to bradykinin resembles more closely
      the response of mammals rather than the predominantly pressor response seen in
      teleost fish. Sturgeon bradykinin produced a strong and concentration-dependent
      (EC50 = 4.7 +/- 0.7 x 10(-10) M) relaxation of rings of vascular tissue from the
      sturgeon ventral aorta that had been pre-contracted with acetylcholine. The data
      indicate that sturgeon tissues are particularly responsive to native bradykinin
      and suggest that the kallikrein-kinin system may have evolved before the
      appearance of the neopterygians (gars, bowfin and teleosts).

PMID- 9622018
TI  - Regional distribution of urocortin-like immunoreactivity and expression of
      urocortin mRNA in the human brain.
AB  - Regional distribution of urocortin-like immunoreactivity (UCN-LI) in the human
      brain was studied by radioimmunoassay and was compared with that of corticotropin
      releasing hormone (CRH). In addition, the expression of UCN mRNA was examined by
      reverse transcriptase-polymerase chain reaction (RT-PCR) method. UCN-LI was
      detected in every region of brain examined, including hypothalamus, pons,
      cerebral cortex, and cerebellum. The concentrations of UCN-LI in the human brain
      were approximately 3 pmol/g wet weight in any brain region, and no marked
      regional difference was noted. On the other hand, the highest concentrations of
      CRH-LI were found in the frontal cortex, temporal cortex, and hypothalamus and
      the lowest in the pons. Reverse phase high-performance liquid chromatography of
      the UCN-LI in the human brain extract showed two immunoreactive peaks; one peak
      eluting earlier and one in the position of synthetic human UCN. RT-PCR showed
      that UCN mRNA was expressed in every region of brain examined. These findings
      indicated that UCN and UCN mRNA were widely expressed in the human brain.

PMID- 9622019
TI  - The degradation of corticotropin-releasing factor by enzymes of the rat brain
      studied by liquid chromatography-mass spectrometry.
AB  - The corticotropin-releasing factor (CRF; 41 amino acid residues) is a major
      regulatory peptide in the response to stress and is distributed over many regions
      of the brain. We have studied the enzymatic degradation of CRF and related
      peptides by the CRF-degrading enzyme(s) of the rat brain (CRF-DA) by liquid
      chromatographic-mass spectrometric technique and by online tandem mass
      spectrometric experiments. Peptide fragments of the human/rat CRF (1-41)
      generated by the CRF-DA of the particulate cell fraction were separated and
      structurally assigned. Major sites of enzymatic attack were identified at the P1
      positions Ser1, Thr11 , His13, Leu15, Arg23, Arg35, and Lys36 with Leu15 as the
      site of primary cleavage. The CRF-DA was shown to be dominated by a
      metalloendopeptidase activity inhibited by O-phenanthroline and EDTA. The
      cytosolic fraction generated a similar degradation pattern with a pronounced
      cleavage at the Arg35 position.

PMID- 9622020
TI  - Heterogeneity in POMC expression among explanted melanotropes decreases with time
      in culture and bromocriptine treatment.
AB  - The biosynthetic activity of rat intermediate lobe melanotropes in vivo is
      inhibited by stimulation of dopamine D2 receptors. Individual melanotropes are
      innervated differentially by dopaminergic axons and vary in their levels of pro
      opiomelanocortin (POMC) mRNA. We tested the hypothesis that placement of the lobe
      in primary culture, which removes the inhibitory innervation, would increase POMC
      mRNA levels and abolish the heterogeneity in POMC expression. POMC mRNA levels
      increased successively in untreated melanotropes when tested on culture Days 10,
      16, and 20; however, some heterogeneity in POMC expression persisted. If treated
      with a D2 receptor agonist (1 microM bromocriptine) from culture Day 1, POMC mRNA
      levels were decreased significantly throughout the testing period when compared
      to untreated cells with the same time in culture. Although some melanotropes
      still expressed high POMC levels, preparations appeared more homogeneous by Day
      20. Melanotrope responses were reversible, since POMC mRNA levels were down
      regulated by application and up-regulated by withdrawal of a D2 receptor agonist.
      A short agonist treatment resulted in subpopulations that responded differently
      to the agonist, possibly representing a mechanism for fine-tuning peptide hormone
      release.

PMID- 9622021
TI  - In vitro effect of alpha-MSH administration on steroidogenesis of prepubertal
      ovaries.
AB  - The effects of alpha-MSH on ovarian progesterone (P) and estradiol (E2) release
      were investigated. To this purpose, different doses of alpha-MSH were
      administered to prepubertal ovaries incubated under the following conditions: ten
      5 min-pulses of perfusion medium (PM) plus LH at 160 ng/ml each one followed by a
      25-min period of PM. The medium of the treated group contained alpha-MSH (0.1, 1,
      5, or 10 microg/ml, in saline solution) and the control group saline solution. PM
      was assayed for P and E2 release. The area under the curve, pulse amplitude and
      width, and basal hormonal release were calculated for each hormone profile. With
      respect to P release, an increase in the areas under the curve could be observed
      in ovaries treated with 1, 5 and 10 microg alpha-MSH/ml. This increment generally
      coincided with an increase in P pulse amplitude and/or basal P release. The P
      pulse width was not modified. No significant variations were observed in the
      parameters under analysis with regard to E2 release. It is concluded that alpha
      MSH administered to prepubertal ovaries could exert a physiological role through
      stimulation of P release.

PMID- 9622022
TI  - Role of corticotropin-releasing factor and substance P in pressor responses of
      nuclei controlling emotion and stress.
AB  - The wide distribution of corticotropin-releasing factor (CRF) and substance P
      (SP)-immunoreactive cell bodies, nerve terminals and corresponding receptors in
      pressor nuclei controlling emotion and stress implies that CRF and SP may play
      important roles in pressor responses of these nuclei; hence CRF or SP was
      microinjected into these nuclei respectively in Wistar male rats anesthetized
      with urethane to test this possibility. Microinjection of CRF into nucleus
      amygdaloideus centralis, nucleus paraventricularis, nucleus ventromedialis,
      lateral hypothalamus-perifornical region, periaqueductal gray matter, nucleus
      parabrachialis, locus coeruleus or rostral ventrolateral medulla respectively
      could evoke pressor responses (but CRF injection into nucleus dorsomedialis could
      not elicit significant pressor responses). Injection of substance P into all the
      above nuclei could also elicit hypertensive responses of different magnitudes,
      whereas normal saline injection into these nuclei had no effect. These results
      indicate that both CRF and SP in the above mentioned nuclei may play important
      roles in hypertension induced by prolonged emotional stress.

PMID- 9622023
TI  - Transglutaminase-synthesized gamma-(glutamyl5) spermidine derivative of substance
      P is a selective tool for neurokinin-2 receptors characterization.
AB  - The ability of transglutaminase-synthesized 1,3-diaminopropane, spermidine (Spd),
      spermine (Spm), and monodansylcadaverine gamma-(glutamyl5)derivatives of
      substance P (SP) to produce bronchoconstriction was investigated. In urethane
      anaesthetized guinea pigs, intravenous injections of SP derivatives contracted
      differently bronchial smooth muscle and caused hypotension. The most effective
      bronchoconstrictor among SP analogs was the gamma-(glutamyl5)Spd derivative of SP
      (Spd-SP; EC50 = 5.3 nmol/kg), which was more potent than the native peptide (EC50
      = 26.5 nmol/kg). In contrast, the gamma-(glutamyl5)Spm derivative of SP (Spm-SP)
      was found completely unable to cause bronchoconstriction and was significantly
      less effective than SP in determining hypotension. The contractile effect of Spd
      SP and Spm-SP was investigated in vitro on rat isolated colon, a well
      characterized preparation rich in NK2 receptors. In addition, Spd-SP was tested
      on the endothelium-denuded rabbit pulmonary artery (RPA) and the hamster isolated
      trachea (HT), both tissue preparations containing only a single functional
      receptor subtype (NK2A and NK2B, respectively). The results obtained showed that
      Spd-SP recognizes NK2 receptors occurring on rat isolated colon more effectively
      (EC50 = 11 nM) than the native peptide (EC50 = 45 nM). Conversely, Spm-SP evokes
      a contractile response less effective than that elicited by SP (EC50 = 312 nM).
      Furthermore, Spd-SP (0.1-10 microg kg(-1)) produced a concentration-dependent
      contraction of both HT and RPA, exhibiting a potency respectively 12 and 30 times
      higher than SP in contracting HT and RPA. Our results indicate that the
      introduction of a Spd moiety at the level of glutamine-5 of SP gives rise to an
      analog that possesses a different capability to recognize NK2 receptors than the
      parent peptide. Moreover, since Spd-SP seems to contract more effectively RPA
      than HT, we conclude that it preferentially recognizes the NK2A receptor subtype.

PMID- 9622024
TI  - Binding characteristics of YM087, an AVP receptor antagonist, in rhesus monkey
      liver and kidney membranes.
AB  - The binding characteristics of YM087, a nonpeptide vasopressin (AVP) V1A and V2
      receptor antagonist, were studied using 3H-AVP binding to rhesus monkey liver and
      kidney membrane preparations. Both membrane preparations exhibited one class of
      high-affinity binding sites. However each membrane's receptors were different,
      with Kd values of 0.57 and 1.11 nM, Bmax values of 59.6 and 147 fmol/mg protein
      for liver and kidney, respectively. AVP receptor agonist or antagonist binding
      inhibition studies confirmed that these receptors belong to the V1A (liver) and
      V2 (kidney) subtypes. YM087 showed high affinity for both liver V1A and kidney V2
      receptors with Ki values of 26.3 and 9.89 nM, respectively. These results show
      that YM087 is a potent, nonpeptide dual AVP V1A and V2 receptor antagonist, and
      would be a powerful tool for understanding the physiologic roles of AVP.

PMID- 9622025
TI  - Enhanced depressor and hyperemic responses to calcitonin gene-related peptide in
      spontaneously hypertensive rats.
AB  - Intravenous (i.v.) bolus injection of calcitonin gene-related peptide (CGRP)
      caused a depressor response, which was significantly larger in 12-week-old
      spontaneously hypertensive rats (SHR) than in Wistar-Kyoto rats (WKY). CGRP also
      caused decreases in carotid and hindquarter vascular resistance, the magnitude of
      which was larger in the carotid than the hindquarter. In both regions, the
      vasodilator response to CGRP was significantly larger in SHR than WKY. Plasma
      CGRP level was significantly lower in SHR than WKY. These results suggest that
      depressor and vasodilator responses to CGRP are enhanced in SHR and that
      decreased plasma CGRP level in SHR may contribute to the enhanced responses.

PMID- 9622026
TI  - Developmental changes in binding sites and reactivity for CGRP and VIP in porcine
      pulmonary arteries.
AB  - During postnatal adaptation pulmonary arteries dilate. CGRP and VIP are pulmonary
      vasodilators. In this report, porcine lungs from newborn to adult were studied.
      Radiolabeled ligand binding and autoradiography showed CGRP binding sites on the
      endothelium of pulmonary arteries and veins, which increased postnatally, and VIP
      binding sites on smooth muscle, which decreased. Isolated conduit arteries
      relaxed normally (initially endothelium dependent) in response to CGRP from
      birth. VIP first caused relaxation at 10 days and was endothelium dependent. Age
      related changes in receptor binding density were not always reflected in an
      appropriate alteration in pharmacological response.

PMID- 9622027
TI  - Presence of atrial natriuretic peptide in two desert rodents: comparison with
      rat.
AB  - Atrial natriuretic peptide (ANP) was characterized and assayed in plasmas,
      hearts, and brains of two Algerian desert rodents, Psammomys obesus and Meriones
      libycus along with vasopressin, which was assayed in hypophyses and hypothalami.
      Using reverse-phase high-performance liquid chromatography and radioimmunoassay,
      we showed, in plasmas and hearts of both species of desert rats, the presence of
      peptides similar to rat N- and C-terminal ANP but in lower amounts than in Wistar
      rats. Conversely, C-terminal ANP was abundantly detected in hypophyses from
      Meriones libycus rats. As these peptides, through their diuretic and natriuretic
      activities, are involved in body fluid regulation and electrolyte balance, the
      reduction of ANP stores in both plasmas and hearts suggests that diuresis and
      natriuresis are lowered in both species of mammals adapted to arid environments.
      This could occur because of the vasopressin-mediated adaptation, but also in
      response to the low ANP involvement in hydro-osmotic regulations, even in
      Psammomys, which has a dietary salt loading. On the other hand, the higher C
      terminal ANP contents in the hypophysis of Meriones than in Psammomys and Wistar
      rats remain to be understood.

PMID- 9622028
TI  - Affinity of neuropeptide FF analogs to opioid receptors in the rat spinal cord.
AB  - Several high-affinity analogs of neuropeptide FF (Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe
      NH2, NPFF) exhibiting both supraspinal anti-opioid and spinal analgesic
      activities were studied for their abilities to interact with specific mu, delta,
      and kappa opioid binding in the rat spinal cord. Measurements by quantitative
      receptor autoradiography in the superficial layers of the spinal cord revealed
      that NPFF analogs tested have only a low affinity for opioid receptors since Ki
      values ranged from 5 to 400 microM. Taking into account the high efficacy of NPFF
      after intrathecal injection, these results indicate that analgesic effects of
      NPFF did not result from opioid receptor stimulation.

PMID- 9622029
TI  - Plasma proenkephalin peptide F and human B cell responses to exercise stress in
      fit and unfit women.
AB  - In vitro studies have connected immune cell function to Peptide F. The primary
      purpose of this investigation was to examine the responses of plasma Peptide F
      and epinephrine along with the changes in B cell antibody production in vivo in
      physically fit and unfit women in response to physical exercise on a cycle
      ergometer at 60% and 80% of peak oxygen consumption. Seven aerobically fit and
      eight untrained (i.e., unfit) women between the ages of 18 and 30 volunteered to
      participate in this investigation. Blood samples (analyzed for plasma Peptide F
      and epinephrine along with the number of antibody-producing B cells) were
      obtained 24 hours prior to the exercise session, pre-exercise, during each
      exercise intensity, and five minutes post-exercise. The fit group had a
      significantly higher plasma Peptide F concentration after the 80% exercise
      intensity along with significantly higher numbers of antibody producing B cells
      compared to the unfit group. The results of this investigation show that
      physically fit women have an enhanced secondary response of B cells to a specific
      antigen under conditions where Peptide F is increased. Such data demonstrate that
      physical fitness as promoted by the Public Health Service (e.g., Healthy People
      2000) influences the underlying hormonal and immune cell responses when
      challenged by physical exercise stress.

PMID- 9622030
TI  - The effect of FMRFamide analogs on [35S]GTP-gamma-S stimulation in squid optic
      lobes.
AB  - Pharmacological study of Phe-Met-Leu-Phe-amide (FMRFa) receptors is hindered by
      the lack of selective ligands. The classification of these selective ligands is
      further hampered by the limited availability of functional assays. In this study,
      we evaluated several synthetic FMRFa analogs for agonist and antagonist activity
      by measuring their abilities to produce [35-S]-GTP-gamma-S stimulation or to
      inhibit FMRFa-induced [35S]-GTP-gamma-S binding in squid optic lobes. Analogs
      included acetyl-Phe-norLeu-Arg-Phe-amide (acFnLRFa), desamino-Tyr-Phe-Leu-Arg
      amide (daYFLRa), desamino Tyr-Phe-norLeu-Arg-Phe-amide (daYFnLRFa), desamino Tyr
      Phe-norLeu-Arg-[TIC]-amide (daYFnLR[TIC]a), desamino Tyr-Trp-norLeu-Arg-amide
      (daYWnLRa), (D)-Tyr-Phe-norLeu-Arg-Phe-amide (D)-YFnLRFa), Phe-Leu-Arg-Phe-amide
      (FLRFa), and the D-amino acid analogs of FMRFa (D-FMRFa, F-(D)-MRFa and FM-(D)
      RFa). For agonist studies, full dose-response curves were generated and analyzed
      for potency and efficacy (maximal percent effect). FMRFamide as well as analogs
      ac-FnLRFa, daYFnLRFa, daYFnLR[TIC]a, D-YFnLRFa, FLRFa, and (D)-FMRFa stimulated
      [35S]-GTP-gamma-S binding. Analogs daYWnLRa, daYFLRa, F-(D)-MRFa, and FM-(D)-RFa
      failed to stimulate either [35S]-GTP-gamma-S binding or to inhibit FMRFa-induced
      [35S]-GTP-gamma-S binding. The rank order of potency was daYFnLRFa > or =
      daYFnLRF[TIC]a > acFnLRFa > (D)YFnLRFa > FLRFa > or = FMRFa >> (D)-FMRFa. The
      order of efficacy was daYFnLRFa = acFnLRFa = (D)-YFnLRFa > FLRFa = FMRFa > or =
      (D)-FMRFa > or = daYFnLRF[TIC]a. Peptide analog daYFnLR[TIC]a was less
      efficacious (59% maximal stimulation) than analogs daYFnLRFa, acFnLRFa, and (D)
      YFnLRFa (113-146% maximal stimulation). A maximal concentration of daYFnLR[TIC]a
      (10 microM) reduced daYFnLRFa, acFnLRFa, and (D)-YFnLRFa induced [35S]-GTP-gamma
      S stimulation, indicating that daYFnLR[TIC]a is a partial agonist at the receptor
      stimulated by the FMRFamide analogs. Analysis of the structural requirements
      needed for promoting [35S]-GTP-gamma-S binding show that elongation (i.e.,
      daYFnLRFa, D-YFnLRFa) or modification of Phe1 (ac-FnLRFa) leads to increased
      efficacy and potency. Moreover, elimination of the C-terminal Phe (daYWnLRa,
      daYFLRa,) leads to a loss of biological activity. However, substitution with L
      1,2,3,4 tetrahydroisoquinoline-3-carboxylic acid, a rigid analog of the C
      terminal Phe (daYFnLR[TIC]a), leads to decreased efficacy but not loss of
      potency. The data suggest that immobilization or modification of the C-terminal
      Phe may produce highly selective and potent FMRFamide antagonists. These results
      agree with published receptor radioligand studies and indicate that the [35S]GTP
      gamma-S assay may be useful in classifying novel FMRFamide-selective ligands.

PMID- 9622031
TI  - Differential effects of endomorphin-1, endomorphin-2, and Tyr-W-MIF-1 on
      activation of G-proteins in SH-SY5Y human neuroblastoma membranes.
AB  - Endomorphin-1 (Tyr-Pro-Trp-Phe-NH2) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH2),
      peptides recently isolated from bovine and human brain, have high affinity and
      selectivity for mu opiate receptors. They share sequence similarity with the
      endogenous opiate-modulating peptide Tyr-W-MIF-1 (Tyr-Pro-Trp-Gly-NH2). The
      efficacies of these endogenous peptides and of the enkephalin analog DAMGO were
      compared by measuring their effects on the binding of guanosine-5'-O-(-gamma
      [35S]thio)triphosphate ([35S]GTPgammaS) to G-proteins in membranes from SH-SYSY
      human neuroblastoma cells. DAMGO, endomorphin-1, and endomorphin-2 stimulated
      [35S]GTPgammaS binding dose dependently, with maximal effects of 60 +/- 9%, 47 +/
      9%, and 43 +/- 6% stimulation above basal and ED50 of 49 +/- 8 nM, 38 +/- 8 nM,
      and 64 +/- 13 nM, respectively. Tyr-W-MIF-1 showed only a small stimulation of
      binding (5% stimulation above basal, ED50 = 2 microM). When given in combination
      with the other opioids, however, Tyr-W-MIF-1 attenuated their ability to activate
      G-proteins. Thus, the endogenous opioids endomorphin-1 and endomorphin-2 activate
      G-proteins similarly to the synthetic agonist DAMGO, but the structurally similar
      peptide Tyr-W-MIF-1 produces only minimal stimulation of G-proteins.

PMID- 9622032
TI  - Parallel stimulations of in vitro and in situ [35S]GTPgammaS binding by
      endomorphin 1 and DAMGO in mouse brains.
AB  - Metabotropic activities of endomorphin 1, a candidate for endogenous mu-opioid
      receptor ligands, were examined in comparison with the actions of [D-Ala2, N-Me
      Phe4, Gly5ol]-enkephalin/DAMGO, a well-known synthetic mu-opioid agonist.
      Endomorphin 1 stimulated [35S]GTPgammaS binding to synaptic membranes from the
      mouse amygdala in a naloxone-reversible manner. DAMGO had the same effect in such
      preparations. In in situ [35S]GTP-gammaS binding experiments using brain
      sections, both endomorphin 1 and DAMGO similarly stimulated this binding in
      specific cellular locations throughout the brain regions. These findings strongly
      support the view that endomorphin 1 selectively acts on a mu-opioid receptor.

PMID- 9622033
TI  - Neokyotorphin formation and quantitative evolution following human hemoglobin
      hydrolysis with cathepsin D.
AB  - In vitro human hemoglobin hydrolysis by cathepsin D was investigated. The
      quantitative evolution of neokyotorphin following the hydrolysis was determined
      by high-performance liquid chromatography coupled with a photodiode array
      detector. Spectral comparisons allowed us to identify neokyotorphin in the
      hydrolysates all along the hydrolysis. Second order derivative spectrometry was
      used in order to verify the presence of tyrosine in the peptide. This provided
      informations about the mechanism of cathepsin D activity towards hemoglobin.
      Moreover it confirmed that hemoglobin could appear as a precursor of some
      bioactive peptides following proteolytic degradation.

PMID- 9622034
TI  - Dynorphin A(6-12) analogs suppress thermal edema.
AB  - Dynorphin A (Dyn A) is a 17-residue opioid peptide derived from prodynorphin
      precursors found in mammalian tissues. Removal of Tyr1 from Dyn A produces a
      peptide that is more potent than Dyn A in attenuating the acute phase of the
      inflammatory response, as measured by inhibition of heat-induced edema in the
      anesthetized rat's paw (exposure to 58 degrees C water for 1 min). Dyn A(2-17),
      however, no longer interacts with opioid receptors. It was postulated that the
      non-opioid anti-inflammatory actions of Dyn A(2-17) may reside in Dyn A(6-12);
      that is, Arg-Arg-Ile-Arg-Pro-Lys-Leu. here we report on the activities of Dyn A(6
      12) analogs modified by substitutions on the N terminus, by single N-methyl
      substitution and by single replacement of residues by alanine. The results
      indicated that the minimal sequence required for an anti-edema ED50 of <1.0
      micromol/kg i.v. was anisoyl-Arg6-Arg7-Xaa8-Arg9-Pro10)-Xaa11-+ ++Xaa12-NH2. A
      prototype, p-anisoyl-[D-Leu12] Dyn A(6-12)-NH2, with an ED50 of 0.20 micromol/kg
      i.v. compared to an ED50 of 0.08 micromol/kg i.v. for Dyn A(2-17), was selected
      for further tests of biological activity. This analog, like Dyn A(2-17), lowered
      blood pressure in anesthetized rats. In a model of neurogenic inflammation,
      produced by antidromic stimulation of the vagus in the anesthetized rat, p
      anisoyl-[D-Leu12] Dyn A(6-12)-NH2, 0.23 micromol/kg i.v., attenuated the
      negativity of tracheal tissue interstitial pressure (Pif), which normally
      develops after nerve stimulation. Modulation of interstitial pressure may be the
      mechanistic basis for the anti-edema properties of these Dyn A(6-12) analogs.

PMID- 9622035
TI  - Efficacy of oral dalargin-loaded nanoparticle delivery across the blood-brain
      barrier.
AB  - The Leu-enkephalin dalargin normally does not penetrate the blood-brain barrier
      (BBB) when given intravenously. To transport dalargin across the blood-brain
      barrier, the peptide was adsorbed onto the surface of poly(butyl)cyanoacrylate
      nanoparticles and coated with polysorbate 80. After systemic administration the
      central analgesia was measured by hot plate test. Furthermore, nanoparticles were
      fabricated with different stabilizers. After the adsorption of the peptide on
      polysorbate 85 stabilized nanoparticles analgesia was observable after
      intravenously and oral application even when nanoparticles were not coated. Thus,
      our data support the usefulness of nanoparticles as a method to deliver drugs to
      the brain.

PMID- 9622036
TI  - Mass spectrometry of peptides in neuroscience.
AB  - This review focuses on the contributions of modern mass spectrometry to
      neuropeptide research. An introduction to newer mass spectrometric techniques is
      provided. Also, the use of mass spectrometry in combination with high-resolution
      separation techniques for neuropeptide identification in biological samples is
      illustrated. The amino acid sequence information that is important for the
      identification and analysis of known, novel, or chemically modified neuropeptides
      may be obtained using mass spectrometric techniques. Because mass spectrometry
      techniques can be used to reflect the dynamic properties associated with
      neuropeptide processing in biological systems, they may be used in the future to
      monitor peptide profiles within organisms in response to environmental challenges
      such as disease and stress.

PMID- 9622037
TI  - Anticardiolipin antibodies in clinical conditions associated with a risk of
      thrombotic events.
AB  - Anticardiolipin antibodies (ACAs) of IgA, IgG, and IgM isotypes were measured
      using an enzyme-linked immunosorbent assay (ELISA) in patients with SLE, and in
      other groups of subjects with a higher or lower risk of developing thrombosis.
      IgA ACAs were present in high titers in all groups and had little discriminant
      value in predicting thrombotic risk. In patients without the lupus anticoagulant
      (LAC) with conditions in which a thrombotic tendency was a feature (primigravidae
      with preeclampsia or intrauterine growth retardation, patients with angina or
      acute myocardial infarction, those on anticoagulant therapy for apparently
      spontaneous thrombosis, and patients with Behcet's syndrome in whom there was a
      history of thrombosis) ACAs of all isotypes were present in 44/191 (23%). In
      patients in whom a thrombotic tendency was not a feature (normal controls,
      primigravidae with normal deliveries, patients with rheumatoid arthritis, and
      with Behcet's syndrome in whom there was no thrombotic history) 22/241 (9%) had
      ACAs. Although ACAs were more likely to be present in a subset of patients
      without systemic lupus erythematosus (SLE) and/or the LAC, their presence was a
      poor discriminator of increased risk of thrombosis.

PMID- 9622038
TI  - Effects of electric footshock and water immersion restraint stresses on
      fibrinolytic parameters in the plasma of rats.
AB  - Wistar rats were exposed to electric footshock (ES) or water immersion restraint
      stress (WS). Blood was taken immediately after, 24, or 48 hours after the stress.
      The stomachs of rats taken 1 hour after stress application indicate that there
      were many bleeding spots in the stomachs of WS rats, but practically no visible
      bleeding spots in the stomachs of ES rats. Plasma levels of t-PA antigens
      increased in ES rats up to 24 hours after the stress, but the t-PA antigen levels
      decreased up to 48 hours in ES rats. There were no changes in t-PA activities in
      plasma of WS rats, but the levels in ES rats decreased immediately and 48 hours
      after the stress. PAI activity did not change immediately after WS but increased
      24 hours after the stress. There was no change in PAI activity in ES rats up to
      48 hours. ELT did not change in ES rats, but prolonged in WS rats at 24 hours
      after the stress. There were significant negative correlations between t-PA
      antigen levels or activities and ELT in control rats. No correlation was observed
      in ES or WS rats between t-PA antigen levels and ELT, and no correlation was
      shown in WS rats between t-PA activities and ELT. Plasma levels of catecholamines
      increased at the 20-minute period during ES, which may not explain the delayed
      effects of ES on hemostatic balance. Plasma levels of arginine vasopressin
      increased significantly immediately after the shock up to 2 hours, indicating
      that the stress was conveyed to the hypothalamus during the stress application.
      These results may indicate that some stressors induce an increase or decrease in
      the local balance of fibrinolytic activities, resulting in bleeding or thrombosis
      in the local vessels. Such changes may not be detected in the general circulation
      due to the neutralization of locally induced fibrinolytic changes or the
      involvement of other hepatically originated hemostatic factors induced by
      stressors.

PMID- 9622039
TI  - Platelet count, anti-heparin/platelet factor 4 antibodies and tissue factor
      pathway inhibitor plasma antigen level in chronic dialysis.
AB  - We studied 50 chronic dialysis patients with end-stage renal disease. Mean
      platelet count was within normal limits. An inverse linear correlation was
      observed between pre-dialysis platelet count and serum creatinine (r=0.304,
      p=0.038). Dialysis caused a decrease in platelet count (216+/-80x10(9)/L, pre;
      198+/-68, post; p=0.0001), and the higher the pre-dialysis platelet count, the
      greater the decrease (r=0.623, p=0.0001). Post-dialysis triglyceride decreased
      (1.67+/-1.27 mmol/L, pre; 1.23+/-0.96, post; p=0.0001). Tissue factor pathway
      inhibitor (TFPI) antigen plasma level was higher in uremic patients than in
      controls (114+/-42 ng/ml vs. 64+/-12, p=0.0001). TFPI increased 2.3 times
      following dialysis and such an increase was directly correlated with post
      dialysis plasma heparin concentration (r=0.571, p=0.0002) and inversely
      correlated with post-dialysis triglyceride variation (r=0.407, p=0.005). Six of
      fifty patients (12%) had anti-heparin/platelet factor 4 antibodies (Hab), 3 IgG,
      and 3 IgM. Female sex and the use of cuprophane membranes were more frequent
      among Hab-positive patients (p=0.0001), while a lower percentage of them were on
      anti-aggregating drugs as compared to Hab-negative patients (p=0.002). Only one
      Hab-positive patient was slightly thrombocytopenic and none showed bleeding or
      thrombotic manifestations. Serum albumin and y globulin decreased following
      dialysis in Hab-positive patients, while the opposite was seen in those Hab
      negative (-2.47+/-1.72 g/L, vs. 0.21+/-1.77, p=0.001 and -0.48+/-0.60 g/L vs.
      0.64+/-0.97, p=0.007, respectively). In vivo factors other than Hab are involved
      in the development of heparin-induced thrombocytopenia. Besides a blunted
      immunological response, increased levels of TFPI, the use of anti-aggregating
      drugs, and the observed behavior of serum proteins might play a role in this
      regard.

PMID- 9622040
TI  - Thromboembolic complications several days after a single-dose administration of
      aspirin.
AB  - The antithrombotic properties of acetyl salicylic acid (ASA) used at current
      doses are largely demonstrated. However, our previous study showed unexpected
      thrombotic potencies associated with the use of this drug. In this study we
      investigate the effect of aspirin on an experimental thrombosis induced by laser
      beams, according to its in vivo plasma concentration. Experiments were done on
      nine groups of seven Wistar male rats. The groups are defined by the delay
      between aspirin administration time and the laser-induced thrombosis time.
      Results from this study showed an enhancement of thromboembolic complications
      when thrombosis was induced 8 or 10 days after aspirin administration; the number
      of emboli and the duration of embolization are increased, compared to the control
      group. The prothrombotic properties of ASA demonstrated in this study, might
      limit its therapeutic benefit and might explain thromboembolic complications
      observed in some ASA-treated patients. These results also suggest a biological
      monitoring several days after aspirin administration to patients.

PMID- 9622041
TI  - Comparison of the antithrombotic effects of FK633, GPIIb/IIIa antagonist, and
      aspirin in a guinea pig thrombosis model.
AB  - Antiplatelet and antithrombotic effects of FK633 (a GPIIb/IIIa antagonist) and
      aspirin were compared. FK633 at 0.32 mg/kg i.v. or aspirin at 10 mg/ kg i.v.
      inhibited ex vivo collagen-induced aggregation by >50% for 1 hour in guinea pigs.
      However, aspirin was very weak in inhibiting ADP-induced aggregation. In vivo
      antithrombotic effects of FK633 and aspirin were compared using a FeCl3-induced
      carotid artery thrombosis model in guinea pigs. Pretreatment with 0.32 mg/kg i.v.
      of FK633 significantly prevented occlusive thrombus formation, but aspirin at 10
      mg/kg i.v. did not. In thrombolysis experiments, adjunctive use of FK633 (0.32
      mg/kg i.v.) with rt-PA (0.3 mg/kg bolus+1.0 mg/kg/hr) achieved reperfusion in
      five of five animals without reocclusion. Aspirin (10O mg/kg i.v.) with rt-PA
      also achieved reperfusion in three of five animals with high incidence of
      reocclusion. These results suggest that FK633 may be a more effective
      antithrombotic agent than aspirin due to its agonist-independent antiplatelet
      effects.

PMID- 9622042
TI  - Heparin-releasable endothelial cell-associated tissue factor pathway inhibitor
      (TFPI) is increased in the coronary circulation after coronary spasm in patients
      with coronary spastic angina.
AB  - Tissue factor pathway inhibitor (TFPI) is a physiological regulator of the
      extrinsic coagulation cascade. Coronary spasm can alter endothelial cell
      properties in the coronary artery with resultant thrombosis. To determine whether
      coronary spasm affects plasma TFPI level, we measured the heparin-releasable
      endothelial cell-associated TFPI (heparin-releasable TFPI) (ng/ml) in the
      coronary sinus and the aortic root before and after coronary spasm induced by an
      injection of acetylcholine in 18 patients with coronary spastic angina, and
      before and after myocardial ischemia induced by rapid atrial pacing in 18
      patients with stable exertional angina, and in 17 control subjects with normal
      coronary arteries and no coronary spasm. Heparin-releasable TFPI level in the
      coronary spastic angina group significantly increased in the coronary sinus (1
      22+/-46 to 147+/-63, p<0.001) after the ischemic event but not in the aortic root
      (113+/-44 to 121+/-58). The level in the coronary sinus and the aortic root
      remained unchanged after the ischemic event in the stable exertional angina group
      and after the injection of acetylcholine in the control group. The coronary sinus
      arterial difference in the amount of the heparin-releasable TFPI significantly
      increased after the ischemic event only in the coronary spastic angina group
      (10+/-18 to 26+/-18, p<0.002). Our result suggested that heparin-releasable TFPI
      is increased in the coronary circulation after coronary spasm.

PMID- 9622043
TI  - Recombinant coagulation factor IX: glycosylation analysis and in vitro conversion
      into human-like sialylation pattern.

PMID- 9622044
TI  - Clonidine does not potentiate the antipsychotic effects of neuroleptics in
      chronically ill patients.
AB  - Clonidine is a centrally acting antihypertensive and has been prescribed widely
      for more than 20 years. Because it decreases central norepinephrine activity,
      clonidine has been investigated as an antipsychotic. In most of the preliminary
      studies, clonidine was tested as the sole antipsychotic agent. We performed a
      double-blind, placebo-controlled, crossover study to compare a placebo plus a
      neuroleptic to clonidine plus a neuroleptic in a group of 16 chronically
      psychotic patients. Of these 16, 3 dropped out secondary to side effects of the
      clonidine and 1 withdrew from the study. The clonidine dosage varied from 0.2 to
      0.6 mg per day. The concurrent neuroleptic (one of the following: haloperidol,
      thiothixene, thioridazine, mesoridazine, or fluphenazine) averaged 34 mg per day
      of haloperidol equivalents. Symptoms were monitored using the Psychiatric
      Symptoms Assessment Scale. The data provided evidence that a
      clonidine/neuroleptic combination was not more effective than a neuroleptic alone
      in this group of patients. These data suggest that the central antinorepinephrine
      activity of a neuroleptic is not potentiated further by clonidine.

PMID- 9622045
TI  - Betaxolol in anxiety disorders.
AB  - Betaxolol, a long-acting beta-adrenergic blocker that enters the central nervous
      system, was examined for therapeutic effects on the persistent anxiety of anxiety
      disorders. Prior studies of beta-blockers examined only agents that were short
      acting or did not enter the brain. Betaxolol was administered to 31 patients in
      open trials. Of 13 outpatients, 11 had generalized anxiety disorder (GAD) and 2
      had adjustment disorder with anxiety. Five with GAD had concurrent panic
      disorder. Of 18 inpatients, 16 had GAD and 2 had adjustment disorder with
      anxiety. Betaxolol doses were increased until the patient responded or declined
      further dosage. Severity was rated on a 4-point global scale. Before betaxolol,
      all were moderately or severely ill. In all patients with panic disorder panic
      attacks stopped within 2 days (p<0.001). Anxiety decreased to no more than
      marginally ill in 85% of outpatients (p<0.0001) and all inpatients (p<0.0001).
      Betaxolol doses were usually 5 mg once or twice daily; four inpatients took 10 to
      20 mg twice daily. In sum, betaxolol administration was rapidly followed by
      improvements that were easily noticed by the doctor, even in patients with
      longstanding anxiety and obsessive-compulsive personality disorder. Preliminary
      observations in posttraumatic stress disorder are similar.

PMID- 9622046
TI  - Mixed symptoms and syndromes of anxiety and depression: diagnostic, prognostic,
      and etiologic issues.
AB  - Patients with comorbid symptoms of anxiety and depression are common in clinical
      practice, and yet they continue to pose a diagnostic and therapeutic challenge to
      clinicians and researchers alike. This article is intended as a comprehensive
      review of current knowledge derived from a vast body of clinical research
      regarding the diagnostic interrelationships of anxiety and depressive disorders
      at both syndromal and subsyndromal levels. The prognostic implications of
      comorbidity are also reviewed. Biological linkages between the two disorders are
      explored, and recent biological theories attempting to explain and integrate the
      two disorders are presented as well. The article concludes with suggestions for
      further research.

PMID- 9622047
TI  - Risperidone-induced galactorrhea associated with a prolactin elevation.
AB  - We report on the occurrence of galactorrhea associated with a prolactin elevation
      within weeks of treatment with risperidone. One of our patients was switched to a
      typical antipsychotic, with an improvement in the galactorrhea. The other patient
      was continued on risperidone due to a robust response, while her galactorrhea was
      partially treated with bromocriptine. The mechanism of prolactin elevation with
      risperidone is unclear. These cases suggest the need for further studies.

PMID- 9622048
TI  - Dose-dependent valproic acid thrombocytopenia in bipolar disorder.
AB  - The increased use of anticonvulsants in the treatment of bipolar disorders
      necessitates a greater appreciation of potential complications from these agents.
      The authors present a bipolar disorder patient with dose-dependent valproic acid
      thrombocytopenia and suggest treatment strategies.

PMID- 9622049
TI  - Olanzapine-induced weight gain.

PMID- 9622050
TI  - Lack of thyroid abnormalities in mood-disordered adolescent inpatients.

PMID- 9622051
TI  - Cardiac tumors: a current clinical and pathological perspective.
AB  - Cardiac tumors, primary or secondary, are rare but important cardiovascular
      abnormalities. Their potentially lethal course and the possibility of cure with
      propitious excision makes their diagnosis challenging and consequential.
      Therefore, in order to achieve diagnostic and therapeutic adequacy, clinicians
      should be knowledgeable of cardiac tumor pathology as well as their frequently
      atypical clinical presentations. For centuries, neoplasias of the heart have been
      considered a rarity and a postmortem diagnostic curiosity. Their incidence in
      autopsy series varies between 0.0017 and 0.19% in unselected patients (Heath,
      1968; Straus et al., 1945; Wold et al., 1980). Antemortem recognition of
      intracardiac tumors by clinical and electrocardiographic findings was not
      recognized until 1934 (Barnes et al., 1934). In 1951, the diagnosis of an
      intracavitary left atrial tumor was confirmed with angiography (Goldberg et al.,
      1952), and the first successful excision of a heart tumor, a left atrial myxoma,
      was reported in 1955 (Crafoord, 1955). It was only later in the 1970s, when M
      mode and 2-D echocardiography became available together with other imaging
      techniques such as CT and MRI, that antemortem diagnosis of intracardiac tumors
      became more feasible.

PMID- 9622052
TI  - Human prostate carcinogenesis.
AB  - Prostate cancer is a major medical problem that is expected to affect over
      300,000 American men and cause over 40,000 deaths in 1997. Despite its widespread
      prevalence and because of the difficulties in clinical diagnosis and treatment of
      the disease, the etiological mechanism underlying prostate carcinogenesis remains
      poorly understood. Elucidation of the mechanism of prostate tumorigenesis has
      been slowed by a lack of tumor tissues and the limited number of human cell lines
      available for study. In vitro human cell models to study the molecular biology of
      prostate cancer progression are urgently needed. Normal human prostate cells
      require immortalization to provide a practical system for transformation studies.
      Neoplastic transformation of human prostate epithelial cells in culture has been
      achieved recently in a stepwise fashion--immortalization of primary cells in
      culture and conversion of the immortalized cells to a tumorigenic state. Reviewed
      here are the steps involved in the neoplastic transformation of human prostate
      cells. To provide an insight into the molecular and genetic mechanisms involved
      in the conversion of normal cells to a neoplastic state of growth, the authors
      have attempted to put into perspective the history of human prostate epithelial
      cell transformation by a combination of carcinogenic agents, and to discuss the
      current state-of-the-art in transformation of human prostate epithelial cells in
      culture.

PMID- 9622053
TI  - Role of Crk oncogene product in physiologic signaling.
AB  - v-Crk is a member of the family of adaptor-type signaling molecules that consist
      mostly of SH2 and SH3 domains. The cellular homologs of v-Crk includes CrkI,
      CrkII, and CrkL; these have been isolated from species ranging from lower
      vertebrates to man. Crk-family proteins are involved in a variety of signaling
      cascades such as those of growth factor receptor, integrin, T-cell receptor, B
      cell antigen receptor, and cytokines. It has been postulated that the primary
      function of Crk is to recruit cytoplasmic proteins in the vicinity of tyrosine
      kinases through SH2-phosphotyrosine interaction. Thus, the output from Crk
      depends on the SH3-binding proteins, which include the C3G guanine nucleotide
      exchange protein for Rap1, Abl tyrosine kinase, DOCK180, and the Sos guanine
      nucleotide exchange protein for Ras. The variety of the Crk-binding proteins
      indicate the pleiotropic function of Crk.

PMID- 9622054
TI  - Role of focal adhesion proteins in signal transduction and oncogenesis.
AB  - The focal adhesion is a structure that is formed when a cell comes into contact
      with the extracellular matrix. Originally, the focal adhesion was thought to only
      provide structural support for the actin-based cytoskeleton of the cell. However,
      the last decade has yielded considerable information linking various protein
      components of the focal adhesion to signal transduction pathways. Examples of
      focal adhesion proteins include the catalytically active p125FAK, SH2-containing
      tensin, and the multifunctional LIM domain-containing paxillin. The interactions
      of focal adhesion proteins may be altered after cellular transformation. This
      review details how certain focal adhesion proteins are associated in cellular
      signaling as well as transformation. The importance of various GTP-binding
      proteins in interacting with and forming the focal adhesion, and the influence
      they have on neoplastic transformation, are discussed. A key feature of this
      review is how oncogenes and their respective oncoproteins affect the focal
      adhesion. Classically, v-src transformation of adherent cells has been studied to
      characterize focal adhesions, namely, because of the distinct morphological
      changes that occur in the focal adhesion concomitantly with src transformation.
      Similarly, the BCR/ABL oncogene, which causes chronic myelogenous leukemia, leads
      to adhesion defects and can alter the properties of focal adhesion proteins.
      Thus, we describe some of the relevant interactions between the focal adhesion
      and the Src and BCR/ABL oncoproteins, respectively.

PMID- 9622055
TI  - The Cbl family of signal transduction molecules.
AB  - This review summarizes the current knowledge about the structure, expression, and
      signaling function of Cbl. A mutant Cbl form (v-Cbl) was first identified as the
      product of the Cas-NS-1 murine retrovirus that induces lymphomas and leukemias.
      Two members of the Cbl family have since been defined in mammals (c-Cbl and Cbl
      b), one in C. elegans (Sli-1) and one in Drosophila (D-Cbl). There is high
      conservation between Cbl species in the amino-terminal region that contains a
      putative phosphotyrosine binding domain and a Ring finger motif. In the carboxy
      terminal region, mammalian Cbl forms share a proline-rich stretch, conserved
      tyrosine residues, and a leucine zipper. Cbl participates in signaling by
      receptor protein tyrosine kinases, as well as antigen and cytokine receptors that
      signal via associated cytoplasmic protein tyrosine kinases. Cbl is recruited to
      the tyrosine kinase module of these receptors and tyrosine phosphorylated after
      cellular activation. It functions as a scaffold protein and associates with SH2
      and SH3 domain containing molecules, including the Crk adaptor family and Vav. By
      analogy with the C. elegans homologue Sli-1, Cbl is proposed to be a negative
      regulator of receptor tyrosine kinase signaling. After deletion mutation in a
      region close to the Ring finger, c-Cbl becomes oncogenic. Such mutations are
      suggested to result in a structural alteration, allowing oncogenic mutants to
      displace wild-type c-Cbl from the receptor complex and to abrogate its negative
      regulatory function.

PMID- 9622056
TI  - Antigen processing/presenting and oncogenesis.
AB  - It has been established in recent years that a number of tumor cell types express
      tumor antigens, yet the host's immune system fails to recognize them. The antigen
      processing/presenting machinery, which plays a crucial role in generating an
      immune response, and possible causes for its inability of processing/presenting
      tumor antigens are reviewed. These causes are related to the expression of major
      histocompatibility complex molecules, costimulatory molecules, and tumor antigens
      by tumor cells, and the types of cytokines produced. Therapeutic measures include
      transfecting tumor cells with genes that encode major histocompatibility complex
      and costimulatory molecules, cytokines, and tumor antigens. In addition, tumor
      peptide vaccines are evaluated. However, developing an immune response to tumor
      antigens carries with it the risk of autoimmune disease.

PMID- 9622057
TI  - Is 2-methoxyestradiol an endogenous estrogen metabolite that inhibits mammary
      carcinogenesis?
AB  - Catechol estrogens (2- or 4-hydroxyestradiol and 2- or 4-hydroxyestrone) are
      chemically reactive estrogen metabolites that are O-methylated to less polar
      monomethyl ethers by catechol-O-methyltransferase, an enzyme present in many
      tissues such as the liver, kidney, brain, placenta, uterus, and mammary gland. In
      the present report, we review recent studies on the antitumorigenic and
      antiangiogenic effects of exogenously administered 2-methoxyestradiol in vitro
      and in vivo. We also discuss data that suggest that endogenous formation of 2
      methoxyestradiol (and its 2-hydroxyestradiol precursor) may have a protective
      effect on estrogen-induced cancers in target organs. Although the molecular
      mechanism of action of 2-methoxyestradiol is not clear, we suggest that some
      unique effects of 2-methoxyestradiol may be mediated by a specific intracellular
      effector or receptor that is refractory to the parent hormone, estradiol.
      Additional research is needed to identify factors that regulate the metabolic
      formation and disposition of 2-methoxyestradiol in liver and in target cells and
      to evaluate the effects of modulating 2-methoxyestradiol formation on estrogen
      induced carcinogenesis.

PMID- 9622058
TI  - Genomic changes in endometrial polyps associated with tamoxifen show no evidence
      for its action as an external carcinogen.
AB  - Eighty-eight endometrial specimens from 36 postmenopausal breast cancer patients
      treated with tamoxifen were investigated cytogenetically and molecularly using
      fluorescence in situ hybridization with appropriate probes for the HMGIC and
      HMGIY genes. Twenty control specimens, 10 endometrial polyps, and 10 endometrial
      biopsy specimens were investigated in the same way. Of the 88 specimens, 44 were
      from endometrial polyps; 3 were from endocervical polyps; 7 were from cystic
      endometrium; 30 were from normal or atrophic endometrium, normal endocervix, or
      myometrium; and 4 were from endometrial carcinomas. Chromosome investigation of
      the endometrial polyps showed the nature of the chromosome changes in tamoxifen
      induced polyps to be the same as that in the controls and in sporadic endometrial
      polyps described in the literature. HMGIC and HMGIY gene rearrangements in both
      groups were identical as shown by fluorescence in situ hybridization, which also
      allowed for the detection of seven hidden paracentric inversions involving 12q15,
      one of which occurred in a cystic endometrium. The carcinomas did not exhibit any
      of these changes. Because abnormal expression of HMGIC or HMGIY as a consequence
      of structural chromosome changes in 12q15 or 6p21, respectively, is invariably
      associated with benign neoplasia, tamoxifen-associated endometrial polyps are
      unlikely to undergo further malignant transformation, and a mode of action of
      tamoxifen as an external carcinogen is unlikely.

PMID- 9622059
TI  - Prostate-specific amplification of expanded polyglutamine expression: a novel
      approach for cancer gene therapy.
AB  - For cancer gene therapy, it is of primary importance to develop a system to
      sufficiently and selectively express therapeutic genes in cancer cells. In this
      study, we showed that an approximately 5.3-kb promoter region of the prostate
      specific antigen (PSA) gene can replicate the endogenous expression pattern,
      although its expression is very weak. We then developed a novel two-step
      transcriptional activation system in which the PSA promoter drives an artificial
      transcriptional activator, GAL4-VP16 fusion protein, and it in turn activates
      transgene expressions under the control of GAL4-responsive elements. By using
      this system, transgene expressions can be greatly augmented while maintaining
      prostate-specific expression. Finally, we applied this system to drive an
      expanded polyglutamine, a potent proapoptotic molecule, to induce apoptosis
      selectively in PSA-positive prostate cancer cells. This novel system would
      provide an ideal approach for cancer gene therapy applicable not only to prostate
      cancer but to other cancers as well.

PMID- 9622060
TI  - Adenovirus-mediated wild-type p53 gene transfer down-regulates vascular
      endothelial growth factor expression and inhibits angiogenesis in human colon
      cancer.
AB  - Recent studies have indicated that angiogenesis may be regulated, in part, by p53
      tumor suppressor gene function. We hypothesized that wild-type p53 replacement
      would down-regulate vascular endothelial growth factor (VEGF) expression and
      inhibit angiogenesis. KM12L4 and SW620, human colon cancer cell lines with p53
      mutations, were transduced with a replication-defective adenoviral vector
      containing the wild-type p53 gene (Ad5/CMV/p53). Reverse transcription-PCR
      confirmed the presence of p53 in Ad5/CMV/p53-transduced cells. Transduction of
      colon cancer cells with wild-type p53 decreased VEGF RNA expression compared with
      that of controls. The decrease in VEGF expression in SW620 cells was dose
      dependent, with a 49% decrease observed at a multiplicity of infection of 50, and
      a 71% decrease observed at a multiplicity of infection of 100. Similar effects
      were seen in KM12L4 cells. VEGF supernatant protein levels were significantly
      reduced compared with those in nontransduced controls 48 h after the introduction
      of wild-type p53. Ad5/CMV/p53 inhibited tumor cell-induced angiogenesis in vivo.
      Restoration of wild-type p53 expression may decrease tumor growth by inhibiting
      the angiogenic response. These findings may explain, in part, the bystander
      effect seen with p53 tumor suppressor gene therapy.

PMID- 9622061
TI  - Ataxia-telangiectasia and T-cell leukemias: no evidence for somatic ATM mutation
      in sporadic T-ALL or for hypermethylation of the ATM-NPAT/E14 bidirectional
      promoter in T-PLL.
AB  - The ATM gene deficient in ataxia-telangiectasia, a recessive multisystem disease
      associated with a high risk of lymphomas and leukemias, was found previously to
      be inactivated in a rare sporadic malignancy, T-cell prolymphocytic leukemia (T
      PLL), which is often associated with cytogenetic aberrations of chromosome 14.
      The ATM gene was shown to sustain frequent loss-of-function mutations in T-PLL
      tumor cells, consistent with functioning as a tumor suppressor gene in this
      leukemia. To investigate the possibility of nonmutational or nonrecombinational
      mechanisms of T-PLL development, we have used bisulfite genomic sequencing to
      analyze DNA methylation in the putative bidirectional promoter region of the
      closely linked ATM and NPAT/E14 genes within the CpG island at 11q22-q23. We show
      that this region is completely demethylated in lymphocytes expressing ATM;
      however, no extensive hypermethylation was found in 9 T-PLL tumor DNA samples
      without evidence of ATM/p53 mutations. Because acute T-cell lymphoblastic
      leukemias (T-ALL) were also observed in ataxia-telangiectasia patients and T-ALL
      tumor cells contain chromosome 14 abnormalities, 19 presentation samples of T-ALL
      patients were analyzed for ATM mutations. Although T-ALL patients exhibited rare
      nucleotide substitutions not previously found in ATM, all were identified in the
      germ-line, indicating constitutional polymorphisms, potentially confined to
      ethnic subpopulations. The absence of somatic nucleotide changes in ATM in T-ALL
      as compared with T-PLL suggests a distinct pattern of genetic events in the
      development of the two leukemias.

PMID- 9622062
TI  - Germ-line deletion involving the INK4 locus in familial proneness to melanoma and
      nervous system tumors.
AB  - Joint predisposition to malignant melanoma and nervous system tumors (NSTs) is a
      puzzle. Several melanoma susceptibility genes have been identified, including
      p16, a clustered tumor suppressor. However, the molecular bases of inherited
      proclivity to NSTs in the absence of a recognizable genetic syndrome are unknown.
      We analyzed two families with joint proneness to melanoma and NSTs in view of
      genetic linkage and identification of the causal molecular lesions. Highly
      informative linkage markers were used for segregation analyses of the
      predisposition alleles in the two pedigrees. Characterization of the molecular
      lesions required hemizygosity mapping based on microsatellite markers physically
      mapped to contigs of the 9p21 region and a Southern blot approach using several
      PCR-generated probes. Both families were found to be allelic and linked to p16
      markers. In the family segregating the melanoma/NST syndrome, a large germ-line
      deletion ablated the whole p16, p19, and p15 gene cluster (or INK4 locus),
      whereas a more circumscribed molecular lesion disrupting p16 and p19 but leaving
      p15 unaltered segregated with the melanoma-astrocytoma syndrome (MIM 155755). Our
      results suggest that multiple cancer susceptibility in these two families ensues
      from contiguous tumor suppressor gene deletion. Indeed, known phenotypes
      associated with germ-line p16 mutations and an apparent correlation between the
      deletion span and tumor spectrum in the two families suggest a new model of
      cancer pathogenesis based on the inactivation of contiguous tumor suppressor
      genes, an alternative to the established pleiotropic effects of single-gene
      disruption.

PMID- 9622063
TI  - Intratumoral heterogeneity of von Hippel-Lindau gene deletions in renal cell
      carcinoma detected by fluorescence in situ hybridization.
AB  - Although chromosome 3p deletions are considered an initial event in clear cell
      renal cell carcinoma (RCC), the reported prevalence of 3p deletions is highly
      variable. Because molecular analyses may be influenced by intratumoral
      heterogeneity, this study was performed to evaluate the genetic heterogeneity of
      the von Hippel-Lindau (VHL) gene (on 3p25.5) in RCC. Fifty-three clear cell and
      papillary RCCs were examined by dual-labeling fluorescence in situ hybridization
      with probes for the VHL gene and chromosome 3 centromere. The results were
      compared with histopathological phenotype, proliferative activity (Ki-67 labeling
      index) and 8p/17p deletions (both suggested to be linked to RCC progression). A
      clear-cut VHL deletion (in more than 40% of cells) was detectable in 69% of clear
      cell RCCs but was not detectable in nine papillary RCCs. A considerable genetic
      heterogeneity of VHL deletions was seen in clear cell RCCs including VHL-deleted
      subpopulations with different chromosome 3 counts within individual tumors as
      well as populations with and without VHL deletions. 8p22 and 17p13 deletions
      (each of which were detected in 18% of clear cell RCCs) were both linked to VHL
      deletions. However, 8p and 17p deletions were not associated with tumor grade,
      stage, or Ki-67 labeling index. The data indicate that some clear cell RCCs may
      develop independently of VHL alterations.

PMID- 9622064
TI  - Adenovirus-mediated gene delivery of tissue inhibitor of metalloproteinases-3
      inhibits invasion and induces apoptosis in melanoma cells.
AB  - We have used adenovirus-mediated gene delivery of tissue inhibitor of
      metalloproteinase (TIMP)-1, -2, and -3 to examine their effect on the invasion
      capacity of metastatic melanoma cell lines SK-Mel-5 and A2058. Infection of
      melanoma cells with recombinant replication-deficient adenoviruses coding for
      TIMP-1, TIMP-2, and TIMP-3 resulted in marked secretion of TIMP-1 and TIMP-2 to
      culture medium and accumulation of TIMP-3 to matrix. Overexpression of TIMP-3
      inhibited invasion of SK-Mel-5 and A2058 cells through reconstituted basement
      membrane (Matrigel) even more potently than TIMP-1 and TIMP-2. In addition,
      overproduction of TIMP-3 reduced attachment of melanoma cells to type I and IV
      collagen and fibronectin and resulted in apoptosis in both SK-Mel-5 and A2058
      cells. These results propose a novel role for TIMP-3 in regulation of invasion
      and survival of malignant cells and suggest potential use for TIMP-3 in
      adenovirus-mediated gene therapy of malignant melanoma.

PMID- 9622065
TI  - Characterization of cell cycle checkpoint responses after ionizing radiation in
      Nijmegen breakage syndrome cells.
AB  - Nijmegen breakage syndrome (NBS), which in the past also has been classified as a
      variant of ataxia telangiectasia (AT), is characterized by cancer proneness and
      extreme sensitivity to ionizing radiation. We investigated the DNA damage
      responses of four independent primary NBS fibroblast cell lines. Following a low
      dose of ionizing radiation, p53 is mostly induced with slower kinetics and shows
      more transient induction in NBS fibroblasts. Nonetheless, this damage-induced
      protein appears biologically functional: unsynchronized and synchronized NBS
      cells show a G1 arrest after ionizing radiation as determined by bivariate flow
      cytometry. Neither an AT cell line nor a NBS cell line transformed with human
      papillomavirus genes E6 and E7 shows a G1 arrest. Furthermore, NBS cells show a
      normal G2 block, unlike that shown for AT cells. These data provide a cellular
      distinction between NBS and AT, thereby clearly separating the NBS from the AT
      syndrome.

PMID- 9622066
TI  - Antioxidants reduce cyclooxygenase-2 expression, prostaglandin production, and
      proliferation in colorectal cancer cells.
AB  - Increased expression of cyclooxygenase (COX) and overproduction of prostaglandins
      (PGs) have been implicated in the development and progression of colorectal
      cancer (CRC). Recent observations suggest that reactive oxygen intermediates play
      a role in tumor cell growth regulation and expression of the inducible COX, COX
      2. We therefore evaluated the effects of various antioxidants on COX expression
      and cellular growth in the human CRC cell line HCA-7. The antioxidants
      pyrrolidinedithiocarbamate (PDTC), N-acetylcysteine, 6-hydroxy-2,5,7,8
      tetramethylchroman-2-carboxylic acid (Trolox), and U74006 decreased PG
      production, intracellular redox status, and cellular growth in a concentration
      dependent manner. The decrease in cellular growth was associated with the
      induction of apoptosis. Unlike the selective COX inhibitors 1-[(4
      methylsulfonyl)phenyl]-3-trifluoromethyl-5-[(4-fluoro)phenyl]pyraz ole (SC 58125)
      and (2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide (NS 398) that inhibit COX-2
      catalytic activity, these antioxidants decreased COX-2 expression at the
      transcriptional level. Combined treatment of HCA-7 cells with PDTC and SC 58125
      resulted in an additive decrease in PG levels and anchorage-dependent and 
      independent growth. Furthermore, whereas antioxidants or SC 58125 reduced tumor
      growth in vivo, coadministration of PDTC and SC 58125 resulted in actual tumor
      regression. These results suggest that combined therapy with NSAIDs and
      antioxidants might be useful in the prevention and/or treatment of CRC.

PMID- 9622067
TI  - Evidence for the multifocal origin of bilateral and advanced human serous
      borderline ovarian tumors.
AB  - Borderline ovarian tumors (BOTs), or ovarian tumors of low malignant potential,
      represent a distinct category of epithelial ovarian neoplasms that have a
      clinically more favorable outcome than invasive epithelial ovarian cancer.
      Histologically, BOTs and invasive ovarian carcinomas both show cellular
      proliferation and pleomorphism, but unlike invasive ovarian carcinomas, BOTs lack
      stromal invasion. Although serous BOTs are frequently confined to a single ovary
      at the time of diagnosis, bilateral or extra-ovarian spread occurs in 30-40% of
      cases. The purpose of this study is to determine whether bilateral or
      extraovarian serous borderline lesions are metastatic sites from the original
      tumor, or represent separate primary tumors. DNA specimens from multiple tumor
      sites and normal tissue controls were obtained in eight women with bilateral or
      extra-ovarian serous borderline tumors. The pattern of loss of heterozygosity at
      the androgen receptor locus on the X chromosome was evaluated in the multiple
      tumor sites. In addition, the pattern of X-chromosome inactivation was determined
      using HpaII restriction endonuclease digestion, followed by PCR amplification of
      the androgen receptor locus. Multifocality was determined when alternate patterns
      of X-chromosome inactivation occurred. In two of the eight patients, the left and
      right ovarian tumor sites had different androgen receptor alleles inactivated,
      indicating that the bilateral tumors derived independently. In a third patient,
      the X inactivation pattern in the left ovarian tumor differed from the two
      peritoneal implants, suggesting that the implants were separate primary tumors,
      and not metastatic, from the left ovarian tumor. The remaining five patients had
      the same pattern of loss of heterozygosity and X inactivation in the tumor sites
      studied. These results suggest that bilateral and advanced stage serous BOTs may
      be multifocal in origin. This result is in contrast to invasive epithelial
      ovarian cancer, which has been shown to be unifocal in origin.

PMID- 9622068
TI  - Suppression of tumorigenicity of glioblastoma cells by adenovirus-mediated
      MMAC1/PTEN gene transfer.
AB  - Mutated in multiple advanced cancers 1/phosphatase and tensin homologue
      (MMAC1/PTEN) is a novel tumor suppressor gene candidate located on chromosome 10
      that is commonly mutated in human glioblastoma multiforme and several other
      cancer types. To evaluate the function of this gene as a tumor suppressor, we
      constructed a replication-defective adenovirus (MMCB) for efficient, transient
      transduction of MMAC1 into tumor cells. Infection of MMAC1-mutated U87MG
      glioblastoma cells with MMCB resulted in dose-dependent exogenous MMAC1 protein
      expression as detected by Western blotting of cell lysates. In vitro
      proliferation of U87MG cells was inhibited by MMCB in comparison to several
      control adenoviruses at equal viral doses, implying a specific effect of MMAC1
      expression. Anchorage-independent growth in soft agar was also inhibited by MMCB
      compared to control adenovirus. Tumorigenicity in nude mice of transiently
      transduced mass cell cultures was then assessed. MMCB-infected U87MG cells were
      almost completely nontumorigenic compared to untreated and several control
      adenovirus-treated cells at equal viral doses. These data support an in vivo
      tumor suppression activity of MMAC1/PTEN and suggest that in vivo gene transfer
      with this recombinant adenoviral vector has a potential use in cancer gene
      therapy.

PMID- 9622069
TI  - Activation of nuclear factor kappaB: potential role in metallothionein-mediated
      mitogenic response.
AB  - The antiapoptotic response and enhanced cellular proliferation observed in
      neoplastic cells on overexpression of metallothionein (MT) have been well
      documented. We have investigated the mechanisms associated with this phenomenon
      by using MT inducers that increased MT transcripts and stimulated growth in MCF-7
      cells. A MT antisense phosphorothioate oligonucleotide inhibited growth induction
      by >50%, suggesting a potential role of MT in mediating the mitogenic effects of
      these agents. Mobility shift assays using oligonucleotides encompassing the
      consensus nuclear factor kappaB (NFkappaB) binding site and anti-MT antibody
      revealed activation and a specific interaction of NFkappaB with MT.
      Cotransfection experiments using expression and reporter constructs demonstrated
      that MT caused transactivation of NFkappaB. Gel shift assays using purified
      proteins showed a specific interaction between MT and the p50 subunit of
      NFkappaB. These data indicate that MT may be involved in the interaction of
      NFkappaB with the DNA-binding domain and further suggest a potential role for
      NFkappaB in mediating the antiapoptotic effects of MT.

PMID- 9622070
TI  - Alterations in pancreatic, biliary, and breast carcinomas support MKK4 as a
      genetically targeted tumor suppressor gene.
AB  - Mitogen-activated protein kinase (MAPK) kinase 4 (MKK4) is a component of a
      stress and cytokine-induced signal transduction pathway involving MAPK proteins.
      The MKK4 protein has been implicated in activation of JNK1 and p38 MAPK on
      phosphorylation by conserved kinase pathways. A recent report on the deletion and
      mutation of the MKK4 gene in human pancreatic, lung, breast, testicle, and
      colorectal cancer cell lines suggests an additional role for MKK4 in tumor
      suppression. Both the gene function and the infrequency of mutations might be
      considered atypical for many human tumor suppressor genes, and constitutional DNA
      was not previously available to determine whether the reported sequence variants
      had preceded tumor development. Here, we report that homozygous deletions are
      detected in 2 of 92 pancreatic adenocarcinomas (2%), 1 of 16 biliary
      adenocarcinomas (6%), and 1 of 22 breast carcinomas (when combined with reported
      sequence alterations, 3 of 22 or 14%). In addition, in a panel of 45 pancreatic
      carcinomas prescreened for loss of heterozygosity, one somatic missense mutation
      of MKK4 is observed and confirmed in the primary tumor (2%). Mapping of the
      homozygous deletions further indicated MKK4 to lie at the target of deletion. The
      finding of a somatic missense mutation in the absence of any other nucleotide
      polymorphisms or silent nucleotide changes continues to favor MKK4 as a
      mutationally targeted tumor suppressor gene. Coexistent mutations of other tumor
      suppressor genes in MKK4-deficient tumors suggest that MKK4 may participate in a
      tumor suppressive signaling pathway distinct from DPC4, p16, p53, and BRCA2.

PMID- 9622071
TI  - Apoptosis and tumor angiogenesis in cervical cancer after preoperative
      chemotherapy.
AB  - The correlation between apoptosis and tumor angiogenesis in uterine cervical
      cancer treated by preoperative intraarterial infusion chemotherapy (IAC) was
      investigated. Cervical cancer samples surgically obtained from 12 patients
      (stages Ib-IIIb) receiving IAC and from 10 patients (stages Ib-IIb) receiving no
      chemotherapy and biopsy specimens from the 12 patients before IAC were examined.
      The apoptotic index (AI) was determined with an in situ end-labeling assay.
      Intratumoral microvessel density (IMVD) and thymidine phosphorylase (dThdPase)
      expression were evaluated immunohistochemically using anti-CD34 and anti-dThdPase
      antibodies. AIs were higher in the 8 patients with complete or partial response
      to IAC than they were in the 4 nonchemoresponsive patients and in the 10 patients
      who received no chemotherapy (P < 0.01) and were inversely related to IMVDs (r =
      0.724; P < 0.01). AIs and IMVDs after IAC were higher and lower than those before
      IAC (P < 0.01), respectively. The expression of dThdPase, which has angiogenic
      activity, was markedly decreased after IAC. These results suggest that the
      antitumor effects of IAC are closely associated with apoptotic cell death, which
      may be influenced in part by the extent of tumor angiogenesis inhibition.

PMID- 9622072
TI  - Activation of p73 silent allele in lung cancer.
AB  - p73, a first p53 relative, has recently been identified and demonstrated to be
      monoallelically expressed. This protein shows significant amino acid sequence and
      functional similarities to p53. However, it is unclear whether this protein
      functions as a tumor suppressor. To elucidate the role of p73 in tumor
      development, we investigated the expression of the p73 gene in lung cancer. In a
      comparison between normal lung and tumor tissues, p73 was more highly expressed
      in tumors. Moreover, using a C/T polymorphism in exon 2 for allele-specific
      expression analysis in 21 pairs of lung tumors and matched normal tissues, we
      found that five heterozygous samples exclusively expressed both alleles in tumors
      while showing monoallelic expression in matched normal tissues. This result was
      confirmed by single-nucleotide primer extension analysis. Mutation analysis of
      all 13 coding exons of the gene in 21 lung tumor DNAs revealed several
      polymorphisms, but no tumor-specific mutations were detected. These findings
      strongly suggest that p73 may play an important role in lung tumorigenesis
      through activation of a silent allele and overexpression of wild-type p73 rather
      than as a tumor suppressor.

PMID- 9622073
TI  - Metastasis suppression by the standard CD44 isoform does not require the binding
      of prostate cancer cells to hyaluronate.
AB  - Previous studies from this laboratory have demonstrated that down-regulation of
      the standard CD44 isoform at the mRNA and protein level is associated with the
      acquisition of high metastatic ability within the Dunning R-3327 system of rat
      prostate cancers. Additional studies demonstrated that transfection-induced
      enhanced expression of the standard CD44 isoform suppresses the metastatic
      ability of the AT3.1 Dunning subline without suppressing tumorigenicity. The
      standard CD44 isoform is a major cell surface receptor for the extracellular
      matrix glycosaminoglycan hyaluronate. In this study, an investigation was made to
      resolve whether the ability of the standard CD44 isoform to suppress metastasis
      of the AT3.1 prostate cancer cells critically requires enhanced hyaluronate
      binding. Highly metastatic Dunning AT3.1 rat prostate cancer cells were
      transfected with expression plasmids encoding either the wild-type or mutant
      standard CD44 isoform. The mutant standard CD44 isoform construct encoded a
      protein unable to bind to hyaluronate. Transfectants were isolated and
      characterized with regard to their level of standard CD44 isoform expression,
      hyaluronate binding, tumorigenicity, and metastatic ability. Expression of the
      wild-type standard CD44 isoform increased the hyaluronate binding of prostate
      cancer cells and suppressed their metastatic ability without suppressing their
      tumorigenicity. Expression of the mutant CD44 standard isoform did not increase
      hyaluronate binding; however, it equally suppressed the metastatic ability of the
      AT3.1 prostate cancer cells. These results demonstrate that the metastasis
      suppression by the standard CD44 isoform is independent of its ability to bind to
      hyaluronate.

PMID- 9622074
TI  - Purification and characterization of a tumor lipid-mobilizing factor.
AB  - Cancer patients with weight loss showed urinary excretion of a lipid-mobilizing
      factor (LMF), determined by the ability to stimulate lipolysis in isolated murine
      epididymal adipocytes. Such bioactivity was not detectable in the urine of cancer
      patients without weight loss or in normal subjects. The LMF was purified using a
      combination of ion exchange, exclusion, and hydrophobic interaction
      chromatographies to give a single component of apparent Mr 43,000, which showed
      homology in amino acid sequence with human plasma Zn-alpha2-glycoprotein. Both
      substances showed the same mobility on denaturing and nondenaturing gels and the
      same chymotrypsin digestion pattern, both stained heavily for carbohydrate, and
      they showed similar immunoreactivity. Polyclonal antisera to human plasma Zn
      alpha2-glycoprotein was also capable of neutralization of the bioactivity of
      human LMF in vitro. Using competitive PCR to quantify expression of Zn-alpha2
      glycoprotein, we found that only those tumors that were capable of producing a
      decrease in carcass lipid expressed mRNA for Zn-alpha2-glycoprotein. These
      results provide strong evidence to suggest that tumor production of Zn-alpha2
      glycoprotein is responsible for the lipid catabolism seen in cancer patients.

PMID- 9622075
TI  - Biological evaluation of a lipid-mobilizing factor isolated from the urine of
      cancer patients.
AB  - We have previously shown human lipid-mobilizing factor (LMF) to be homologous
      with the plasma protein Zn-alpha2-glycoprotein in amino acid sequence,
      electrophoretic mobility, and immunoreactivity. In this study, both LMF and Zn
      alpha2-glycoprotein have been shown to stimulate glycerol release from isolated
      murine epididymal adipocytes with a comparable dose-response profile. Both LMF
      and Zn-alpha2-glycoprotein caused a stimulation of adenylate cyclase in murine
      adipocyte plasma membranes in a GTP-dependent process, with maximum stimulation
      at 0.1 microM GTP and with saturation at protein concentrations of >5
      microg/assay. Administration of LMF to exbreeder male mice over a 89-h period
      produced a decrease in body weight without a change in food and water intake.
      Body composition analysis showed a 42% reduction in carcass lipid when compared
      with controls. Treatment of ob/ob mice with human LMF over a 160-h period also
      produced a decrease in body weight, with a 19% reduction in carcass fat, without
      a change in body water or nonfat mass. Serum levels of glycerol and 3
      hydroxybutyrate were significantly increased, as was oxygen uptake by
      interscapular brown adipose tissue, providing evidence of increased lipid
      mobilization and utilization. Human white adipocytes responded to both LMF and
      isoprenaline to the same extent, although the maximal response was lower than
      that for murine white adipocytes. These results suggest that LMF not only has the
      capacity to induce lipid mobilization and catabolism in mice, but it also has the
      potential to exert similar effects in cachectic cancer patients.

PMID- 9622076
TI  - Characterization of CYP1B1 and CYP1A1 expression in human mammary epithelial
      cells: role of the aryl hydrocarbon receptor in polycyclic aromatic hydrocarbon
      metabolism.
AB  - CYP1B1 and CYP1A1 expression and metabolism of 7,12-dimethylbenz(a)anthracene
      (DMBA) have been characterized in early-passage human mammary epithelial cells
      (HMECs) isolated from reduction mammoplasty tissue of seven individual donors.
      The level of constitutive microsomal CYP1B1 protein expression was donor
      dependent (<0.01-1.4 pmol/mg microsomal protein). CYP1B1 expression was
      substantially induced by exposure of the cells to 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) to levels ranging from 2.3 to 16.6 pmol/mg among the seven donors.
      Extremely low, reproducible levels of constitutive CYP1A1 expression were
      detectable in three donors (0.03-0.16 pmol/mg microsomal protein). TCDD
      inductions were larger for CYP1A1, as compared to CYP1B1, demonstrating
      substantial variability in the induced levels among the donors (0.8-16.5
      pmol/mg). Northern and reverse transcriptase PCR analyses corroborate the donor
      dependent differences in protein expression, whereby CYP1B1 mRNA (5.2 kb) was
      constitutively expressed and was highly induced by TCDD (33-fold). The
      contributions of CYP1B1 and CYP1A1 to the metabolism of DMBA were analyzed using
      recombinant human CYP1B1 and CYP1A1, as references, in conjunction with antibody
      specific inhibition analyses (anti-CYP1B1 and anti-CYP1A1). Constitutive
      microsomal activity exhibited a profile of regioselective DMBA metabolism that
      was characteristic of human CYP1B1 (increased proportions of 5,6- and 10,11-DMBA
      dihydrodiols), which was inhibited by anti-CYP1B1 (84%) but not by anti-CYP1A1.
      TCDD-induced HMEC microsomal DMBA metabolism generated the 8,9-dihydrodiol of
      DMBA as the predominant metabolite, with a regioselectivity similar to that of
      recombinant human CYP1A1, which was subsequently inhibited by anti-CYP1A1 (79%).
      A CYP1B1 contribution was indicated by the regioselectivity of residual
      metabolism and by anti-CYP1B1 inhibition (25%). DMBA metabolism analyses of one
      of three donors expressing measurable basal expression of CYP1A1 confirmed DMBA
      metabolism levels equivalent to that from CYP1B1. The HMECs of all donors
      expressed similar, very high levels of the aryl hydrocarbon receptor and the aryl
      hydrocarbon nuclear translocator protein, suggesting that aryl hydrocarbon
      receptor and aryl hydrocarbon nuclear translocator protein expression are not
      responsible for differences in cytochrome P450 expression. This study indicates
      that CYP1B1 is an important activator of polycyclic aromatic hydrocarbons in the
      mammary gland when environmental chemical exposures minimally induce CYP1A1.
      Additionally, certain individuals express low levels of basal CYP1A1 in HMECs,
      representing a potential risk factor of mammary carcinogenesis through enhanced
      polycyclic aromatic hydrocarbon bioactivation.

PMID- 9622077
TI  - Determination of somatostatin receptor subtype 2 in carcinoid tumors by
      immunohistochemical investigation with somatostatin receptor subtype 2
      antibodies.
AB  - We have shown previously that expression of mRNA for somatostatin receptor
      subtype 2 (sst2) detected by in situ hybridization correlates to therapeutic
      outcome in patients with carcinoid tumors treated with somatostatin analogues.
      However, in situ hybridization is laborious and not practical in clinical routine
      work. We have, therefore, developed polyclonal antibodies directed against sst2
      that may be used for immunohistochemistry on tissue specimens. The staining is
      specific and is highly correlated to expression of mRNA for sst2 (P < 0.01) as
      well as to tracer uptake at somatostatin receptor scintigraphy (P < 0.01). There
      is also a good correlation to the therapeutic response in carcinoid patients
      treated with somatostatin analogues (P < 0.05). Of 35 patients with carcinoid
      tumors included in this investigation, 25 stained positive with the antibodies.
      Twenty-two of these were investigated by somatostatin receptor scintigraphy and
      showed tracer uptake in metastases. An additional two patients that did not stain
      with the antibodies showed pathological uptake of the tracer in metastases, which
      might indicate binding to somatostatin receptor subtype 5. None of the 10
      patients without positive immunostaining responded to somatostatin analogue
      treatment, whereas patients with a positive stain had a biochemical response or
      remained stable during treatment. Thus, these antibodies may be used to determine
      the presence of sst2 in carcinoid tumors and to select patients suitable for
      somatostatin analogue treatment. The method is easily applicable in clinical
      practice.

PMID- 9622078
TI  - Increased UDP-glucuronosyltransferase activity and decreased prostate specific
      antigen production by biochanin A in prostate cancer cells.
AB  - Our laboratory has characterized androgen metabolism in an androgen-responsive
      prostate cancer cell line (LNCaP) and showed that these cells accumulated
      intracellular testosterone primarily as glucuronidated metabolites. Using a cell
      free assay with testosterone as substrate, we showed that LNCaP had UDP
      glucuronosyltransferase (UDPGT) activity. Because dietary factors, such as
      flavonoids in soy products, may reduce the risk for hormone-dependent cancers, we
      studied the effects of flavonoids on testosterone-UDPGT activity. LNCaP cells
      were exposed to selected flavonoids for up to 6 days. The increase in UDPGT
      specific activity was linear over this period. Of the compounds tested, biochanin
      A was the most potent, with increased activity at concentration range 0.5-50
      microM. Activities were linear for time and protein and were unaffected by
      flavonoids added directly to the assay. Kinetics studies showed no change in Km
      for testosterone in the face of these large increases in specific activity.
      Cellular metabolism of testosterone reflected the increase in enzyme activity.
      Intact cells treated with biochanin A produced testosterone-glucuronide from
      testosterone at twice the rate of controls. The steroid form of the UDPGT
      transcript was expressed in LNCaP cells and was enhanced in biochanin A-treated
      LNCaP cells. Additionally, biochanin A markedly decreased prostate specific
      antigen (PSA) level against the effect of testosterone on PSA production.
      Biochanin A significantly decreased the testosterone-stimulated release of PSA,
      presumably because biochanin A increased UDPGT and increased the intracellular
      glucuronidation of testosterone. These studies suggest that the modulation of
      hormone metabolism by dietary factors may be important in the prevention and
      treatment of prostate cancer.

PMID- 9622079
TI  - Metabolism of 17-(allylamino)-17-demethoxygeldanamycin (NSC 330507) by murine and
      human hepatic preparations.
AB  - 17-(Allylamino)-17-demethoxygeldanamycin (17AAG), a compound that is proposed for
      clinical development, shares the ability of geldanamycin to bind to heat shock
      protein 90 and GRP94, thereby depleting cells of p185erbB2, mutant p53, and Raf
      1. Urine and plasma from mice treated i.v. with 17AAG contained six materials
      with absorption spectra similar to that of 17AAG. Therefore, in vitro metabolism
      of 17AAG by mouse and human hepatic preparations was studied to characterize: (a)
      the enzymes responsible for 17AAG metabolism; and (b) the structures of the
      metabolites produced. These materials had retention times on high-performance
      liquid chromatography of approximately 2, 4, 5, 6, 7, and 9 min. When incubated
      in an aerobic environment with 17AAG, murine hepatic supernatant (9000 x g)
      produced each of these compounds; the 4-min metabolite was the major product.
      This metabolism required an electron donor, and NADPH was favored over NADH.
      Metabolic activity resided predominantly in the microsomal fraction. Metabolism
      was decreased by approximately 80% in anaerobic conditions and was essentially
      ablated by CO. Microsomes prepared from human livers produced essentially the
      same metabolites as produced by murine hepatic microsomes, but the 2-min
      metabolite was the major product, and the 4-min metabolite was next largest.
      There was no metabolism of 17AAG by human liver cytosol. Metabolism of 17AAG by
      human liver microsomes also required an electron donor, with NADPH being
      preferred over NADH, was inhibited by approximately 80% under anaerobic
      conditions, and was essentially ablated by CO. Liquid chromatography/mass
      spectrometry analysis of human and mouse in vitro reaction mixtures indicated the
      presence of materials with molecular weights of 545, 601, and 619, compatible
      with 17-(amino)-17-demethoxygeldanamycin (17AG), an epoxide, and a diol,
      respectively. The metabolite with retention time of 4 min was identified as 17AG
      by cochromatography and mass spectral concordance with authentic standard. Human
      microsomal metabolism of 17AAG was inhibited by ketoconazole, implying 3A4 as the
      responsible cytochrome P450 isoform. Incubation of 17AAG with cloned CYP3A4
      produced metabolites 4 and 6. Incubation of 17AAG with cloned CYP3A4 and cloned
      microsomal epoxide hydrolase produced metabolites 2 and 4, with greatly decreased
      amounts of metabolite 6. Incubation of 17AAG with human hepatic microsomes and
      cyclohexene oxide, a known inhibitor of microsomal epoxide hydrolase, did not
      affect the production of metabolite 4 but decreased the production of metabolite
      2 while increasing the production of metabolite 6. These data imply that
      metabolite 2 is a diol and metabolite 6 is an epoxide. Mass spectral
      fragmentation patterns and the fact that 17AG is not metabolized argue for the
      epoxide and diol being formed on the 17-allylamino portion of 17AAG and not on
      its ansamycin ring. These data have implications with regard to preclinical
      toxicology and activity testing of 17AAG as well as its proposed clinical
      development because: (a) production of 17AG requires concomitant production of
      acrolein from the cleaved allyl moiety; and (b) 17AG, which was not metabolized
      by microsomes, has been described as being as active as 17AAG in decreasing
      cellular p185erbB2.

PMID- 9622080
TI  - Tyrphostin 4-nitrobenzylidene malononitrile reduces chemotherapy toxicity without
      impairing efficacy.
AB  - In mice, 4-nitrobenzylidene malononitrile (AG1714), which belongs to the
      tyrphostin family, reduced toxicity induced by doxorubicin and cisplatin without
      impairing their antitumor efficacy. AG1714 reduced mortality induced by
      doxorubicin and cisplatin. It prevented, in a dose-dependent manner, cisplatin
      induced nephrotoxicity as assessed by measurement of serum creatinine and blood
      urea nitrogen levels. The protective effect of AG1714 was most pronounced on its
      administration 2 h before cisplatin. AG1714 also prevented doxorubicin-induced
      myelosuppression as assessed by the scoring of bone marrow nucleated cells and
      colony-forming units. Cisplatin-induced small intestinal injury was also
      protected by AG1714 as assessed by histopathological analysis. In vitro, AG1714
      reduced cisplatin-induced apoptosis in a murine fibroblastic cell line (A9) and
      did not affect doxorubicin-induced apoptosis of B-16 melanoma cells. In contrast
      to its protective effect against mortality and injury of normal tissues induced
      by chemotherapy, AG1714 did not impair its antitumor activity and in some tumor
      models enhanced it. This was evident by using the murine tumors B-16 melanoma,
      Lewis lung carcinoma, and methylcholanthrene-induced fibrosarcoma and the human
      tumors SK-28 melanoma and human ovary carcinoma xenografts in nude mice.
      Experiments in which low and high doses of cisplatin and doxorubicin were
      administered to tumor-bearing mice demonstrated that AG1714 reduced mortality of
      high-dose chemotherapy and increased its therapeutic index. AG1714 could provide
      a novel, useful tool to improve chemotherapy by allowing dose intensification.

PMID- 9622081
TI  - Complete regression of well-established tumors using a novel water-soluble poly(L
      glutamic acid)-paclitaxel conjugate.
AB  - Despite an intensive search, few water-soluble paclitaxel derivatives have been
      shown to have a therapeutic index superior to paclitaxel itself. We now report a
      water-soluble poly(L-glutamic acid)-paclitaxel conjugate (PG-TXL) that produces
      striking antitumor effects with diminished toxicity. A single i.v. injection of
      PG-TXL at its maximum tolerated dose (defined as that dose that produces a
      maximum 12-15% body weight loss within 2 weeks after a single i.v. injection)
      equivalent to 60 mg of paclitaxel/kg and at even a lower dose equivalent to 40 mg
      of paclitaxel/kg resulted in the disappearance of an established implanted 13762F
      mammary adenocarcinoma (mean size, 2000 mm3) in rats. (An equivalent dose of PG
      TXL is the amount of conjugate that contains the stated amount of paclitaxel.)
      Similarly, mice bearing syngeneic OCA-1 ovarian carcinoma (mean size, 500 mm3)
      were tumor-free within 2 weeks after a single i.v. injection of the conjugate at
      a dose equivalent to 160 mg of paclitaxel/kg. The conjugate has little if any
      intrinsic tubulin polymerization activity in vitro and is >20 times less potent
      in supporting the growth of a paclitaxel-dependent CHO mutant cell line. PG-TXL
      has a prolonged half-life in plasma and greater uptake in tumor as compared with
      paclitaxel. Furthermore, only a small amount of total radioactivity from PG
      [3H]TXL was recovered as free [3H]paclitaxel in either the plasma or the tumor
      tissue within 144 h after drug injection. Histological studies of tumor tissues
      obtained from mice treated with PG-TXL show fewer apoptotic cells but more
      extensive tumor necrosis as compared with paclitaxel treatment. These data
      suggest that in addition to its role as a carrier for selective delivery of
      paclitaxel to the tumor, PG-TXL exerts distinct pharmacological actions of its
      own that may contribute to its remarkable antitumor efficacy.

PMID- 9622082
TI  - Comparative pharmacology of the novel cyclopropylpyrroloindole-prodrug carzelesin
      in mice, rats, and humans.
AB  - Carzelesin is a novel cyclopropylpyrroloindole prodrug analogue that has recently
      been tested in Phase I clinical trials. To increase our understanding in the
      pharmacology of this new class of cytotoxic drugs, we have compared the
      pharmacology of this drug in mice, rats, and humans. The mouse was the most
      tolerant [10% lethal dose (LD10), 500 microg/kg], the rat was intermediate (LD10,
      40 microg/kg), and humans were the least tolerant species in this series (maximum
      tolerated dose, 300 microg/m2 corresponding to 7.5 microg/kg). In both mice and
      humans, bone marrow toxicity was the primary toxic side effect. Pharmacokinetic
      studies, using a validated high-performance liquid chromatographic procedure,
      revealed that differences in drug clearance and conversion to the active drug (U
      76,074) could not explain the substantial interspecies differences. The area
      under the plasma concentration time curve (AUCs) of carzelesin in mice and rats
      at their LD10s were about 80- and 20-fold higher, respectively, than in humans
      receiving the maximum tolerated dose, whereas the respective AUCs of U-76,074 in
      mice and rats were 50- and 10-fold higher. By using a colony-forming assay with
      bone marrow stem cells from mice and humans, we observed only a 3-fold higher
      toxicity in the latter. Although some of this discrepancy may be explained by the
      fact that the in vitro and the in vivo assays probably reflect the toxicity on
      different populations of colony-forming units, the tolerance of the mouse bone
      marrow in vivo against the very high drug levels in plasma suggest the presence
      of a protective mechanism, which is less active in humans. An important
      consequence of the much higher susceptibility of the human bone marrow for
      carzelesin is that the target plasma levels in humans are much below active
      concentrations achieved in mice, and it is clear that this may compromise the
      successful use of this agent in the clinic. Ultimately, however, the efficacy of
      this drug will be established in Phase II clinical trials.

PMID- 9622083
TI  - Characterization of human anti-high molecular weight-melanoma-associated antigen
      single-chain Fv fragments isolated from a phage display antibody library.
AB  - The human high molecular weight-melanoma-associated antigen (HMW-MAA) meets the
      criteria to be used as an immunogen for immunotherapy of malignant melanoma,
      because it is expressed by a large percentage of melanoma lesions with limited
      heterogeneity and has a restricted distribution in normal tissues. The high
      immunogenicity of the HMW-MAA in BALB/c mice has resulted in the development of a
      large number of anti-HMW-MAA monoclonal antibodies (mAbs). In contrast, no human
      anti-HMW-MAA mAbs have been described. Because the latter may serve as useful
      probes to characterize the antigenic profile of the HMW-MAA, human anti-HMW-MAA
      single-chain fragments of the variable region (scFvs) were isolated by panning
      synthetic scFv library 1 on purified HMW-MAA. Colony hybridization studies and
      nucleotide sequence analysis revealed that scFv 19, 44, 56, and 61 belong to the
      V(H)3 gene family and use the DP-38 germ-line gene segment but have a diverse
      third complementarity-determining region. The human scFvs share some
      characteristics with mouse anti-HMW-MAA mAb but also display some distinct
      features. Like mouse mAbs, human scFvs recognize determinants of HMW-MAA with a
      heterogeneous cellular and molecular distribution in human melanoma cells.
      Furthermore, like some mouse mAbs, human scFvs react with rat neural cells
      expressing the chondroitin sulfate proteoglycan NG2, which shows 81% homology to
      the HMW-MAA. However, at variance with mouse mAbs, the human scFvs show poor
      reactivity with guinea pig melanoma cells. Lastly, human scFv 61 stains both
      benign and malignant lesions of melanocytic origin, although with a lower
      frequency than mouse mAbs. Analysis of the clinical significance of the
      differential expression of the scFv 61-defined determinant in melanoma lesions
      will be facilitated by its reactivity with formalin-fixed melanoma lesions. In
      contrast to mouse mAb, scFv 61 immunoprecipitates the >450-kDa chondroitin
      sulfate proteoglycan component of the HMW-MAA, but not its 250-kDa subunit from
      melanoma cells. Thus, contrary to the current view about the structure of HMW
      MAA, our results demonstrate that the two components are not associated. The
      described scFv antibodies, which represent the first example of human anti-HMW
      MAA antibodies, have provided novel information about the structure of this
      antigen. Future studies will assess the impact of these in vitro-assembled
      antibody fragments on the identification of antigenic determinants of the HMW-MAA
      that can be recognized by the human immune system.

PMID- 9622085
TI  - Peptides derived from self-proteins as partial agonists and antagonists of human
      CD8+ T-cell clones reactive to melanoma/melanocyte epitope MART1(27-35).
AB  - The self-peptide MART1(27-35) derives from the melanocyte/melanoma protein Melan
      A/MART1 and is a target epitope of CD8+ T cells, commonly recovered from tumor
      infiltrating lymphocytes of HLA-A2.1+ melanoma patients. Despite their prevalence
      in such patients, these CTLs generally appear to be ineffective in mediating
      tumor regression in vivo. We have noted previously that numerous peptides from
      both endogenous and foreign proteins are similar to MART1(27-35) and,
      potentially, are capable of productively engaging the T-cell receptors of patient
      derived CTLs. This observation raised the question of whether CTLs in vivo might
      encounter self-peptide analogues of MART1(27-35) that lack full agonist activity,
      perhaps to the detriment of the antitumor CTL response. This possibility was
      evaluated using cloned, patient-derived CTLs with a panel of self-derived natural
      analogues of MART1(27-35) in assays for cytolysis, cytokine release, and
      phosphorylation of T-cell receptor signaling constituents. Several peptides were
      identified as partial agonists, capable of eliciting cytolysis and/or release of
      cytokines tumor necrosis factor-alpha and IFN-gamma but not interleukin 2.
      Several other peptides showed antagonist behavior, effectively inhibiting
      cytolysis of MART1(27-35)-pulsed targets, but did not inhibit killing of cells
      prepulsed with a synthetic, heteroclitic variant of MART1(27-35). Some of these
      antagonists also had lasting effects on interleukin 2 secretion by CTLs under
      experimental conditions involving sequential exposure to ligands. Together, these
      observations suggest that encounters with self-peptide analogues of MART1(27-35)
      may contribute to the peripheral maintenance of these CTLs, while ultimately
      impairing the efficacy of this antitumor T-cell response.

PMID- 9622084
TI  - Multiple roles of interferon-gamma in the mediation of interleukin 12-induced
      tumor regression.
AB  - Administration of recombinant interleukin 12 (IL-12) induces tumor regression
      that is associated with T-cell infiltration in the OV-HM ovarian carcinoma and
      CSA1M fibrosarcoma models. After confirming the blocking of regression by
      injection of anti-IFN-gamma monoclonal antibody (mAb), we investigated the
      mechanisms underlying the requirement of IFN-gamma in T-cell migration and tumor
      regression. T-cell migration was inhibited by injection of anti-IFN-gamma mAb to
      OV-HM tumor-bearing mice prior to IL-12 treatment. We examined, using the
      lymphoid cell migration assay, whether IFN-gamma is required for enhancing the
      migratory capacity of T cells or the T cell-accepting potential of tumor masses
      during IL-12 treatment. Spleen cells from IL-12-treated or untreated OV-HM
      bearing mice were stained in vitro with a fluorescein chemical and transferred
      i.v. into OV-HM-bearing mice that were not treated with IL-12. Migration of donor
      cells was quantitated by counting the number of fluorescent cells on cryostat
      sections of tumor masses from recipient mice. Compared to spleen cells from OV-HM
      bearing mice that were not treated with IL-12, enhanced migration was observed
      for cells from IL-12-treated OV-HM-bearing mice. Anti-IFN-gamma pretreatment of
      donor mice before IL-12 treatment did not reduce the migratory capacity of T
      cells, whereas migration was markedly inhibited in recipient mice injected with
      anti-IFN-gamma. Anti-IFN-gamma pretreatment decreased vascular cell adhesion
      molecule-1 (VCAM-1)-/intercellular adhesion molecule-1 (ICAM-1)-positive blood
      vessels at tumor sites. Consistent with this, migration was also inhibited by
      treatment of recipient mice with either anti-VCAM-1 or anti-ICAM-1 mAb. In
      contrast to the OV-HM model, T-cell migration was not affected in the CSA1M model
      following preinjection of anti-IFN-gamma mAb. In this model, VCAM-1-/ICAM-1
      positive blood vessels existed even after anti-IFN-gamma treatment, although
      tumor regression was completely inhibited. These results indicate that IFN-gamma
      plays two distinct roles in expressing the antitumor efficacy of IL-12: one is to
      support the T-cell acceptability of tumor masses, and the other is to mediate the
      antitumor effects of migrated T cells.

PMID- 9622086
TI  - Identification of a novel gene marker specific for epithelial cells by utilizing
      a 3'-directed cDNA library.
AB  - To achieve reliability of molecular diagnosis using reverse transcription-PCR (RT
      PCR), we established a unique method to search for a novel gene marker specific
      for colonic epithelial cells. Of eight candidate genes selected from a 3'
      directed cDNA library in colonic mucosa, two genes were expressed in normal
      mucosa and cancer of the colon but not in either normal lymph node or normal
      liver tissue. Known sequences of these genes were reported to be located in the
      3' noncoding region, and an additional sequence just upstream to gs04094 (one of
      the candidate genes) was determined. According to the newly identified sequence,
      we designed a new set of primers so that we could distinguish the DNA fragment
      amplified in RT-PCR from that in genomic PCR. RT-PCR using these primers
      demonstrated that gs04094 was expressed in all of 10 primary colon cancers and 4
      liver metastases from colon cancer but in none of 5 normal lymph nodes, 10
      peripheral blood samples, and 2 normal liver tissues. Sensitivity of this method
      was so high as to detect gs04094 mRNA in 10(-6) microg of colon cancer RNA per 1
      microg of normal lymph node RNA. Thus, our strategy to search for a novel gene
      marker using 3'-directed cDNA library proved to be highly efficient.

PMID- 9622087
TI  - Defective bypass replication of a leading strand cyclobutane thymine dimer in
      xeroderma pigmentosum variant cell extracts.
AB  - Xeroderma pigmentosum variant (XP-V) is an inherited disorder resulting in
      hypersensitivity to the cytotoxic, mutagenic, and carcinogenic effects of UV
      light. There is evidence suggesting that XP-V cells carry a defect in the
      replication of UV-induced DNA damage, leading to mutations in genes, e.g., proto
      oncogenes and tumor suppressor genes, of exposed skin cells. Using an in vitro
      assay to quantitatively evaluate replication of the most prevalent UV-derived DNA
      lesion, the cis,syn-thymine dimer (T x T), we have recently found that a T x T
      located on the leading strand can be bypassed by a bona fide human replication
      fork but can also induce fork uncoupling with selective synthesis of the
      undamaged lagging strand (D. Svoboda and J-M. Vos, Proc. Natl. Acad. Sci. USA,
      92: 11975-11979, 1995). We now report the application and further refinement of
      this sensitive assay to the replication of a T x T-containing template by XP-V
      cell-free extracts. In comparison to normal controls, a 10-26-fold deficiency in
      the bypass replication of T x T was observed in XP-V cell extracts. In contrast,
      the disease extracts were as competent as controls for replication of the
      undamaged TT plasmid and for leading T x T-induced fork uncoupling. Besides
      mismatch repair and nucleotide excision repair, the bypass replication defect of
      XP-V may represent a novel category of hereditary mutator phenotypes affecting
      DNA damage processing.

PMID- 9622088
TI  - Clones of normal keratinocytes and a variety of simultaneously present epidermal
      neoplastic lesions contain a multitude of p53 gene mutations in a xeroderma
      pigmentosum patient.
AB  - A patient with xeroderma pigmentosum group C was extensively examined for
      mutations in the p53 gene in normal skin exposed to varying degrees of sunlight
      and in excisional biopsies of basal cell cancer, squamous cell cancer, and
      squamous cell dysplasia. Seventy-three samples were analyzed by microdissection
      of small cell clusters, followed by PCR and direct DNA sequencing. In skin taken
      from areas that most likely had never been exposed to the sun, no mutations were
      found. However, in skin exposed to the sun, we observed a multitude of mutations
      in the p53 gene. UV light-induced mutations were found in all types of lesions,
      as well as in clusters of morphologically normal epidermal cells. Twenty-nine
      distinct mutations were found in exons 5-8, all missense or nonsense, of which 27
      (93%) were UV-specific C --> T or CC --> TT transitions at dipyrimidine sites of
      the nontranscribed strand. Two types of normal skin areas containing p53
      mutations were observed: areas that stain strongly with p53 antibody (p53
      patches) and those that do not stain. Because no silent or intron mutations were
      found in these cell clusters, the alterations in the p53 gene of morphologically
      normal cells are likely to have resulted in a selective growth advantage. The
      poor correlation between mutations and morphological phenotypes demonstrates that
      p53 mutations alone do not determine the phenotypes observed.

PMID- 9622089
TI  - Identification of two common regions of allelic loss in chromosome arm 12q in
      human pancreatic cancer.
AB  - Using the method of microsatellite analysis, we studied 40 tissues with
      pancreatic ductal adenocarcinoma and identified two commonly deleted regions on
      the long arm of chromosome 12. One (region A) was found between D12S81 and
      D12S1719 at 12q21 at a frequency of 67.5%, and the other (region B) was located
      between D12S360 and D12S78 at 12q22-q23.1 at a frequency of 60%; the latter was
      reported previously (M. Kimura, et al. Genes Chromosomes Cancer, 17: 88-93,
      1996). The results of microsatellite analyses were verified by fluorescence in
      situ hybridization. We further analyzed 19 pancreatic cancer cell lines by
      fluorescence in situ hybridization and found that 10 of them showed allelic loss
      at D12S81 and 6 showed allelic loss at D12S360. Yeast artificial chromosome
      contigs were constructed to cover the deleted regions. Region B was completely
      covered by a 650-kb yeast artificial chromosome clone. The frequently deleted
      regions in chromosome 12q in pancreatic cancer that were identified here may
      provide new avenues for isolating novel tumor suppressor genes.

PMID- 9622091
TI  - The Ewing tumor family of peripheral primitive neuroectodermal tumors expresses
      human gastrin-releasing peptide.
AB  - The Ewing tumor family of peripheral primitive neuroectodermal tumors (pPNETs)
      are characterized by chromosomal translocations leading to EWS-ETS gene fusions.
      These hybrid genes express chimeric proteins that are thought to act as aberrant
      transcription factors. We therefore used differential display-PCR to compare gene
      expression patterns in pPNET cell lines with those of other small round cell
      tumors (SRCTs) of childhood. This technique detected differential expression of
      sequences corresponding to human gastrin-releasing peptide (GRP) in pPNET cell
      lines but not in other SRCT cell lines. Subsequent Northern and reverse
      transcription-PCR analysis of SRCT cell lines confirmed GRP positivity in all
      pPNET lines tested. Of primary tumors tested by reverse transcription-PCR, GRP
      expression was found in 7 (44%) of 16 pPNETs but in no other primary SRCTs
      examined. Expression of the GRP receptor gene was demonstrable in 55% of pPNET
      cell lines and 25% of primary pPNET tumors but also in several other SRCTs.
      Radioimmunoassays and immunohistochemistry confirmed expression of bioactive GRP
      peptide in pPNET cell lines and primary tumors, respectively. Moreover, in vitro
      growth of a pPNET cell line was slowed by treatment with a GRP receptor
      antagonist and accelerated by a GRP receptor agonist. GRP is a known autocrine
      growth factor in small cell lung cancer and other neuroendocrine tumors. Its
      expression in pPNETs provides further evidence for a neuroectodermal histogenesis
      of these tumors and suggests that autocrine growth of this family of tumors may
      be at least partially regulated by GRP.

PMID- 9622090
TI  - Expression of early growth response genes in human prostate cancer.
AB  - Early growth-response (EGR) genes are nuclear transcription factors that are
      implicated in regulating cell proliferation. Because these genes show divergent
      expression in various human tumors, we sought to determine their expression in
      nonmalignant and malignant prostate tissues. Total RNA extracted from prostate
      tissues was probed with EGR-1, EGR-2, and EGR-alpha cDNA for Northern blots and
      digoxigenin-labeled cRNA for in situ hybridization. Both Northern blot and in
      situ hybridization analyses demonstrated increased EGR-1, but not EGR-2 or EGR
      alpha expression, in malignant prostate tissue as compared with weak expression
      in nonmalignant tissue. EGR-1 mRNA was quantified in 96 prostate specimens (86
      adenocarcinomas representing different Gleason scores and 10 benign tissues
      showing no histological manifestation of benign prostatic hypertrophy) using in
      situ hybridization with an 35S-labeled cRNA probe. EGR-1 mRNA was expressed at
      significantly higher levels in cancer than in normal prostate (P < 0.001). In
      cancer with Gleason scores 8-10, the expression of EGR-1 was higher compared with
      those of lower Gleason scores (P < 0.005). Immunohistochemical staining showed
      predominately basal cell nuclear EGR-1 protein in prostatic acini. Nuclear
      staining was weak in nonmalignant tissues, more intense in moderately
      differentiated carcinoma, and most intense in poorly differentiated carcinoma.
      These results show that EGR-1 is overexpressed in prostate cancer and suggest a
      role for EGR-1 in prostate cancer growth.

PMID- 9622092
TI  - Inhibition of tumorigenesis and induction of apoptosis in human tumor cells by
      the stable expression of a myristylated COOH terminus of the insulin-like growth
      factor I receptor.
AB  - The insulin-like growth factor I receptor (IGF-IR) plays an important role in
      cell transformation and in protection from apoptosis. Although the wild-type IGF
      IR generally has an antiapoptotic effect, there are reports that its COOH
      terminus may actually generate a proapoptotic signal. Three different expression
      plasmids, all coding for the COOH-terminal sequences of the human IGF-IR, MyCF,
      CF, and MyKCF, were stably transfected into human ovarian carcinoma CaOV-3 cells.
      All three plasmids had no effect on monolayer growth but strongly inhibited
      colony formation in soft agar. Only one of the plasmids, MyCF, expressing the
      last 112 amino acids of the IGF-IR and carrying a myristylation signal, caused
      large-scale apoptosis of CaOV-3 cells in vivo and abrogation of tumorigenesis in
      nude mice. The plasmid expressing the MyCF sequence was also introduced into
      human glioblastoma T98G cells, where it decreased the clonogenicity of cells,
      caused a marked inhibition of colony formation in soft agar, and induced
      apoptosis in vivo. A double mutation at residues 1293 and 1294 of MyCF completely
      abrogated its inhibitory and proapoptotic activities. Neither the
      autophosphorylation of the IGF-IR nor the tyrosyl phosphorylation of IRS-1 was
      affected by the expression of the MyCF plasmid. These and other findings suggest
      that a stably expressed myristylated COOH terminus of the IGF-IR can induce
      apoptosis in human tumor cells in vivo and inhibit tumorigenesis in nude mice by
      a mechanism that avoids the protective effect of the IGF-IR.

PMID- 9622095
TI  - Magnetic resonance evaluation of breast implants and soft-tissue silicone.
AB  - After several years of research in many disciplines, concern for the safety of
      silicone gel-filled breast implants continues. Although systemic effects of
      silicone are debated, there is growing consensus that implant rupture and other
      local breast complications from implants are very real concerns. This paper
      reviews the history of breast augmentation with an emphasis on the great variety
      of implants manufactured during the last generation. A classification scheme
      consisting of 14 breast implant categories is described, and the MR appearance of
      many is illustrated. The MR signs of implant rupture and pitfalls associated with
      those signs are reviewed. Indications and contraindications for MR imaging of
      implants and soft tissue silicone are presented. The author's breast implant and
      soft-tissue silicone MR imaging experience with follow-up surgical experience
      over the last 6 years is summarized and discussed. For 1,626 single lumen
      silicone gel-filled implants imaged, the sensitivity for rupture was 74% and the
      specificity was 98%. For those implants, 64.9% showed no evidence rupture on MR,
      7.9% were indeterminate, and 27.2% were definitely ruptured. Of those that were
      ruptured, 26.2% had silicone outside as well as within the fibrous capsule. Of
      the 442 implants that were shown to be ruptured, 54.8% were in a state of
      uncollapsed rupture, 12.9% minimally collapsed rupture, 4.1% partially collapsed
      rupture, and 28.3% fully collapsed rupture.

PMID- 9622094
TI  - Integration of breast magnetic resonance imaging with breast cancer treatment.
AB  - High-contrast, high-resolution breast magnetic resonance imaging (MRI) is a
      highly accurate method for determining the extent of breast cancer. This
      information can be used to improve therapy by better defining the extent of
      surgery needed, coordinating additional surgery if the initial surgery results in
      positive pathological margins, and determining the effectiveness and extent of
      residual disease following nonsurgical therapy. The use of stereotaxic biopsy and
      localization is an essential component for extending the use of breast MRI in
      therapeutic applications. The clinical value of therapeutic management with
      breast MRI information is expected to result in commercially available tools in
      the near future.

PMID- 9622096
TI  - Lipid- and adenoviral-mediated gene transfer into AIDS-Kaposi's sarcoma cell
      lines.
AB  - Kaposi's sarcoma (KS) is the most frequent malignancy occurring in HIV-positive
      individuals. AIDS-KS is a more aggressive disease than the classical form,
      frequently having a rapid clinical course with numerous serious complications.
      Current systemic treatments for KS, such as chemotherapy and the administration
      of biological modifiers, are complicated by both the drug resistance of the tumor
      and the dose-limiting toxicity of the reagents. The relative accessibility of
      many KS lesions makes the disease a particularly attractive candidate for in vivo
      gene therapy protocols. In this regard, we are interested in delivering
      conditionally toxic suicide and/or antiangiogenic vectors to accomplish targeted
      cell death selectively in AIDS-KS cells. To this end, we examined both cationic
      lipid- and adenoviral-mediated DNA transfection methods. Using the firefly
      luciferase reporter gene, we optimized numerous variables known to be important
      in lipid-mediated DNA transfection, including lipid formulation, the amount of
      lipid and DNA, lipid/DNA ratio, and cell concentration. Under optimal
      transfection conditions, approximately 5-25% of KS cells expressed the introduced
      DNA sequences. Adenoviral-mediated DNA delivery was more efficient than lipid
      delivery in 4 of 5 primary KS cell lines. Two of the lines (RW248 and RW376) were
      transduced by adenovirus at frequencies approaching 100%; two cell lines (CVU-1
      and RW80) gave efficiencies of 20-35%. Two immortalized KS cell lines (KS Y-1 and
      KS SLK) were poorly infected, giving a transduction efficiency of <5%. These
      findings demonstrate that gene transfer into AIDS-KS cells is feasible, and
      suggest that vector strategies may be permissive for translating gene therapy
      approaches for the disease.

PMID- 9622097
TI  - Purine salvage rescue by xanthine-guanine phosphoribosyltransferase (XGPRT)
      potentiates methotrexate resistance conferred by transfer of a mutated
      dihydrofolate reductase gene.
AB  - We have previously shown that successful gene transfer of a mutated dihydrofolate
      reductase (DHFR) cDNA confers resistance to methotrexate (MTX) upon infected
      cells. We constructed a retrovirus vector, DC/SV6S31GPT, which carries both the
      Escherichia coli xanthine-guanine phosphoribosyltransferase gene and the mutated
      Serine 31 DHFR gene. Mouse fibroblast NIH3T3 cells infected with DC/SV6S31 GPT
      are more resistant to MTX than cells infected with DC/SV6S31, which carries the
      Serine 31 DHFR and the neomycin resistance gene cDNA. The mechanism of this
      augmented resistance is the increased salvaging of purines due to expression of
      xanthine-guanine phosphoribosyltransferase, as the augmentation does not occur
      when dialyzed serum, containing little xanthine or guanine, is used for
      cytotoxicity assays. These results indicate that coexpression of a metabolically
      related gene can potentiate the resistance carried by a drug resistance gene.
      This vector may be useful in clinical gene therapy to protect bone marrow from
      the toxic effects of MTX.

PMID- 9622098
TI  - Transfection of interleukin-12 cDNAs into tumor cells induces cytotoxic immune
      responses against native tumor: implications for tumor vaccination.
AB  - Interleukin-12 (IL-12) is a heterodimeric cytokine that is central to the
      development of T helper 1-dependent cellular immunity. Although this cytokine has
      potential therapeutic application as an antineoplastic agent, the systemic
      infusion of IL-12 has led to toxic fatalities; hence, restriction of expression
      of IL-12 to the microenvironment of target tumor cells has obvious appeal. In
      this study, we examined whether tumor cells that were liposome-transfected with
      IL-12 could enhance the induction of cytolytic lymphocyte immunity to the native
      tumor. The plasmid expression vector that we used has several useful features
      including replication to high copy number as an episome and a polycistronic
      message enabling the production of both the p35 and p40 subunits of IL-12 without
      alternative splicing; up to 3 ng/mL/10(6)/48 hours of IL-12 was produced
      following transfection. Tumor cells transfected with IL-12 were superior to
      untransfected cells in the induction of lymphocyte-mediated cytolysis. IL-12
      transfectants induced a heterogeneous population of natural killer, lymphokine
      activated killer, and cytolytic T lymphocytes, the latter of which exhibited
      tumor-specific activity. Our studies suggest that liposome-mediated transfection
      of tumor cells with an episomal, high copy number plasmid vector expressing both
      IL-12 subunits is a promising approach to cancer vaccination, a strategy that
      could be implemented ex vivo in treating malignancies such as metastatic ovarian
      cancer.

PMID- 9622099
TI  - Long-term survival in a rodent brain tumor model by bradykinin-enhanced intra
      arterial delivery of a therapeutic herpes simplex virus vector.
AB  - Recently, it was demonstrated that bradykinin (BK) enhances intracarotid delivery
      of herpes simplex virus type I (HSV) vectors to rat brain tumors, and that gene
      transfer takes place predominantly in the tumor periphery. The aim of the present
      study was to apply these findings to the treatment of experimental rat brain
      tumors. The HSV mutant, hrR3, which is disrupted in the ribonucleotide reductase
      gene, was injected intra-arterially with titers of 1 x 10(8), 1 X 10(9), and 1 x
      10(10) plaque-forming units (pfu) both with and without BK into Fischer 344 rats
      with intracerebral, syngeneic 9L tumors. Starting on day 3 after vector
      administration, animals were treated by intraperitoneal injection of 60 mg/kg/day
      ganciclovir (GCV) or placebo. 1 x 10(10) pfu hrR3 in combination with BK and GCV
      treatment was able to eradicate tumors in 80% of the animals; 1 x 10(9) pfu cured
      40% of the rats, and 1 x 10(8) pfu achieved an extension of survival time but no
      tumor cures. Control groups had 100% mortality within 30 days after injection of
      tumor cells, with the exception of the group with injection of 1 x 10(10) pfu of
      virus and GCV treatment, which had one long-term survivor. No apparent
      complications of this novel type of brain tumor gene therapy were encountered. In
      conclusion, intra-arterial injection of attenuated HSV vectors with blood-tumor
      barrier modification and subsequent systemic GCV application appears to be a
      promising approach for the treatment of malignant brain tumors.

PMID- 9622100
TI  - Enhancement of antitumor immunity by expression of CD70 (CD27 ligand) or CD154
      (CD40 ligand) costimulatory molecules in tumor cells.
AB  - CD70 (CD27 ligand (CD27L)), CD153 (CD30L), and CD154 (CD40L) are members of the
      tumor necrosis factor family of costimulatory molecules and expressed on the
      surface of T cells that are important for both T- and B-cell help. We examined
      the capacity for expression of these tumor necrosis factor family members on
      tumor cells to induce an antitumor response either in the presence or absence of
      interleukin 12. Retroviral vectors were constructed that expressed high levels of
      membrane bound CD70, CD153, or CD154 following infection and selection of the
      murine tumor lines MCA 207 or TS/A. The genetically modified tumor cells
      expressing these molecules were able to stimulate splenic cell proliferation,
      demonstrating that the expressed costimulatory molecules were biologically
      active. When tested for tumor establishment, the expression of either CD70 or
      CD154 was able to slow tumor growth. Similarly, CD70 or CD154 were able to induce
      antitumor immunity at a higher frequency when tested in vaccination and therapy
      models. CD70 was able to induce antitumor immunity at a level similar to CD80
      when tested either in the presence or absence of interleukin 12. Moreover,
      coexpression of CD70 and CD80 was able to synergize the induction of a higher
      frequency of antitumor immunity in a vaccination model. Taken together, our
      results suggest that CD154 and in particular CD70 are able to contribute to the
      induction of the immune response to tumor in murine models and thus may be of use
      for human clinical trials.

PMID- 9622101
TI  - Transduction of normal and malignant oral epithelium by particle bombardment.
AB  - Although genetic approaches to the treatment and prevention of oral cancer are
      being developed, there are no suitable methods of transduction of the oral mucosa
      or early cancers. We therefore tested the technique of particle bombardment for
      its ability to transduce oral cancer cells in vitro and normal epithelium of the
      hamster cheek pouch in vivo. A gene gun was used to transfer a plasmid that
      encoded a marker/suicide fusion gene, beta-galactosidase-thymidine kinase (GAL
      TEK), under control of a CMV promoter. For comparison we used the method of
      lipofection and an adenovirus vector. Particle bombardment transduced up to 13%
      of cells in culture, resulting in a 24.3% reduction in growth in the presence of
      ganciclovir. The efficiency of transduction was similar to that of lipofection
      but was much less than that of the adenovirus vector, which transduced 54% of
      cells and completely inhibited their growth in the presence of ganciclovir.
      Transduction of the hamster cheek pouch by particle bombardment produced
      expression of beta-galactosidase as judged by macroscopic staining, for up to 5
      days. However, histological examination showed that the transduced cells were
      rare and superficial, and that administration of systemic ganciclovir did not
      lead to any changes in the tissue. Improvements in efficiency are necessary
      before the gene gun can be used in the management of oral cancer.

PMID- 9622102
TI  - Inhibition of tumor cell growth by p21WAF1 adenoviral gene transfer in lung
      cancer.
AB  - Gene replacement therapy is potentially a very powerful tool, targeting specific
      molecular mediators of cancer development and progression. p21WAF1 (p21) is a
      cyclin-dependent kinase inhibitor that is induced by p53 upon DNA damage or p53
      overexpression, resulting in cell cycle arrest at the G1 checkpoint and
      inhibition of further cell proliferation. Using a replication-deficient
      recombinant adenovirus (AdV) ((rAd)-p21) as a p21 gene delivery system, we have
      evaluated the effect of p21 introduction in lung cancer cells in vitro as well as
      in vivo. In in vitro experiments, two human non-small cell lung cancer (NSCLC)
      cell lines, NCI-H460 and NCI-H322, showed dose-dependent p21 induction and
      concomitant cell growth inhibition following rAd/p21 infection. Flow cytometric
      analysis of the cell cycle revealed a significant increase in the percentage of
      NCI-H460 cells in G0/G1 following rAd/p21 infection compared with untreated
      cells, suggesting that p21-induced growth inhibition was due to G0/G1 arrest. We
      also tested the therapeutic efficacy of rAd/p21 in an in vivo human NSCLC model
      in SCID mice. Tumor-bearing mice were established by subcutaneous injections of
      NCI-H460 cells and treated by repeated intratumoral injections of rAd/p21.
      Intratumoral delivery of rAd/p21 significantly suppressed tumor growth and
      prolonged survival in rAd/p21-treated mice. Our in vitro and in vivo results
      provide strong preliminary evidence for the growth inhibition of NSCLC by
      rAd/p21. Collectively, these results justify further studies to evaluate the
      efficacy of rAd/p21 for gene therapy in human lung cancer.

PMID- 9622103
TI  - Cell and platelet adhesions on plasma glow discharge-treated poly(lactide-co
      glycolide).
AB  - Surface treatment, such as plasma glow discharge treatment, onto poly(lactide-co
      glycolide) (PLGA) has been investigated to improve the cell-, tissue- and blood
      compatibility. Surface-treated samples were characterized by measurement with a
      contact angle goniometer and electron spectroscopy for chemical analysis (ESCA).
      The contact angles on the plasma-treated PLGA surfaces decreased with increasing
      plasma exposure time from 92 degrees to about 30 degrees, i.e., increased
      hydrophilicity. From the results of ESCA analysis of plasma-treated films, the
      incorporation of oxygen molecules into plasma onto the PLGA surface was observed.
      Cell adhesion and growth on plasma-treated PLGA surfaces were more active than on
      the control. Furthermore, the maximum adhesion and growth of cells in moderate
      hydrophilicity were investigated. Morphology of the adhered platelets on the
      plasma-treated PLGA surface showed less activity than on the control, and the
      number of adhered platelets on the plasma-exposed PLGA sample decreased with
      decreasing water contact angle. It seems that surface wettability of PLGA plays
      an important role in cell adhesion, spreading and growth, and platelet adhesion.

PMID- 9622105
TI  - Bone-implant interface and remaining tissues on the implant surface after push
      out test: an SEM observation.
AB  - The purpose of this study was to compare the morphology of the tissues remaining
      on smooth and dimpled surfaces of a ceramic composite of zirconia-hydroxyapatite
      (TZ-2Y/25HA) with commercially pure titanium (cp Ti) after a push-out test. The
      tissue-material interface was viewed on the specimens without being tested
      mechanically. Cylindrical implants were inserted in the femurs of rabbits for
      three months. Each femur received three implants. After sacrificing the animals,
      the target tissues were collected and divided into two groups: group I was fixed
      in 4% formalin immediately, and group II was tested mechanically by push-out
      before fixation. Specimens were then dehydrated for SEM observation. The results
      showed that no remaining tissue appeared on the smooth cp Ti surface, whereas
      remaining tissues, mineralized and collagenous tissues, were seen on the smooth
      surface of the TZ-2Y/25HA. New bone had grown into and filled the most of dimple
      spaces of both the cp Ti and TZ-2Y/25HA implant. A submicron gap between the bone
      and cp Ti was found, whereas the TZ-2Y/25HA was occasionally in direct contact
      with new bone. Thus TZ-2Y/25HA showed an intimate contact to bone in some areas,
      and cp Ti showed an unmineralized tissue separated interface to bone
      continuously. Taken together, the laser machining seems to have no adverse
      effects on tissue response and is a potential technique for producing micro
      patterned surfaces on dental and medical implants.

PMID- 9622104
TI  - Biochemical analysis of the response in rat bone marrow cell cultures to
      mechanical stimulation.
AB  - Bone marrow cells obtained from rat femora were subjected to primary culture with
      15% fetal bovine serum in the presence of 10(-8) M dexamethasone, and following
      trypsin treatment 5 days later were seeded on Petriperm dishes which have a
      flexible bottom. After a 2-day subculture, a cyclic stress consisting of a 1 s
      stretch (0.3% strain. 0.5 Hz) and a 1 s relaxation for 30 min every day was
      started. Culture tissue was removed on day 2 of the subculture (immediately prior
      to start of stimulation), and then on days 5 and 8 (3 and 6 days after the start
      of stimulation, respectively), at which times dry weight, DNA, alkaline
      phosphatase (ALP) activity, and bone Gla protein (BGP, osteocalcin) were
      measured. Both the dry weight and DNA showed a significant increase in the
      stimulated group by day 8, while the ALP activity showed a significant increase
      by day 5. The BGP began to increase in the stimulated group on day 5 in contrast
      to the control group in which it only increased on day 8. These results support
      the contention that mechanical stimulation promotes the differentiation of
      osteogenic cells and enhances bone formation. Since in this experimental model
      the acceleration of bone formation by mechanical stimulation can be reproduced in
      vitro, it is extremely useful for investigating the mechanisms underlying
      mechanical stimulation.

PMID- 9622106
TI  - Finite elasticity formulations for evaluation of ligamentous tissue.
AB  - The variety of techniques used to measure the cross-sectional area of soft
      connective tissues during mechanical testing lead to inconsistencies in elastic
      descriptions. This study compares the numerical differences between finite
      elasticity (Eularian and Lagrangian formulations) and infinitesimal elasticity
      when considering stress, strain and elastic modulus of ligamentous tissue. Our
      results found stress differences (Cauchy versus Kirchhoff) of 22.4%, strain
      differences (engineering versus Green versus Almansi) as large as 14% and elastic
      modulus differences (Eularian versus Lagrangian) of 44% from ligament tissue
      sampled from rats. It is therefore critical to maintain consistent (energy
      conjugate) elastic formulations for reporting mechanical evaluation of soft
      hydrated tissue.

PMID- 9622107
TI  - Immunogold electron microscopy in situ end-labeling (EM-ISEL): assay for
      biomaterial DNA damage detection.
AB  - We have evaluated a genotoxicity assay that combines in situ end-labeling,
      colloidal gold tagging and electron microscopy in order to adapt it to the
      measurement of in vitro biomaterial-induced genotoxicity. Human lymphocytes were
      cultured in semi-physiological medium which had been previously exposed to
      biomaterial extracts of commercially pure titanium following ISO standards. In
      order to visualize the location of induced DNA strand breaks, cells were then
      exposed to exonuclease III which partially digests and amplifies lesions by
      releasing nucleotides at free 3' hydroxyl ends from nicked double-stranded DNA.
      The resulting single-stranded DNA was allowed to hybridize with short
      oligonucleotides of random sequences including biotinylated dUTP. After random
      priming using Escherichia coli DNA polymerase I, incorporation of biotin-dUTP was
      detected by immunogold binding to the chromatin. Cells exposed to a mutagenic
      concentration of methyl methanesulfonate, as a positive control, showed a
      significantly higher and stronger gold staining than both titanium-exposed and
      unexposed specimens. This assay allows a precise localization and quantification
      of both in vitro DNA breakage and DNA repair. It could provide a powerful tool
      for rapid assessment of the genotoxic potential of new biomaterials.

PMID- 9622108
TI  - Three-dimensional model for the simulation of the HPS electrogram.
AB  - In this paper, simulation of the His-Purkinje system (HPS) electrogram based on a
      three-dimensional model is proposed. The simulation is based on transformation of
      a two-dimensional HPS into a three-dimensional curvilinear system. Furthermore,
      the proposed HPS takes into consideration not just the left bundle branch but
      also the right bundle branch. Results obtained from normal and abnormal HPS
      electrograms show great similarity with those obtained experimentally.

PMID- 9622109
TI  - Future prospects for cardiac assist patients.

PMID- 9622110
TI  - Vancomycin clearance with high-flux dialysis membranes.

PMID- 9622112
TI  - Microsystems in medicine.
AB  - The complexity of modern surgical and analytical methods requires the
      miniaturisation of many medical devices. The LIGA technique and also mechanical
      microengineering are well known for the batch fabrication of microsystems.
      Actuators and sensors are developed based on these techniques. The hydraulic
      actuation principle is advantageous for medical applications since the energy may
      be supplied by pressurised balanced salt solution. Some examples are turbines,
      pumps and valves. In addition, optical sensors and components are useful for
      analysis and inspection as represented by microspectrometers and spherical
      lenses. Finally, plastic containers with microporous bottoms allow a 3
      dimensional growth of cell culture systems.

PMID- 9622111
TI  - Race, life style and renal disease in South Africa.

PMID- 9622113
TI  - A new biosensor for continuous monitoring of the spent dialysate urea level in
      standard hemodialysis.
AB  - This study gives the results in terms of precision and repeatability of a new on
      line urea monitoring system (Ureascan P2 Hospal) capable of measuring the urea
      concentrations in the spent dialysate. The Ureascan P2 Hospal (UP2H), fitted on
      single-pass dialysis machines (Integra-Hospal), functions by the presence of a
      disposable mini-reactor containing urease. The passage through the reactor of a
      minimum quantity of spent dialysate from the filter diluted with a pH 7 buffer
      solution (1 ml/min) increases its ionic strength, which is detected by a
      differential measurement of conductivity in proportion to the urea concentration
      in the dialysis liquid. We studied 13 dialysis sessions, with bicarbonate buffer,
      in 8 anuric patients. From 4 to 7 dialysate samples were taken during each
      treatment to determine the urea and 65 samples were analysed overall. Urea values
      from the UP2H were compared with those measured on the Dimension Du Pont
      analyser. Simple linear regression analysis showed an excellent correlation
      between the 2 measuring methods (r=0.987; p<0.001). The Bland-Altman test gave an
      average difference between the urea values measured with the UP2H and in the
      laboratory of 1.3+/-1.2 mg/dl. The agreement limits between 2 SD were -1.2 mg/dl
      and +3.8 mg/dl respectively. In conclusion, the UP2H we have developed has proved
      to be a reliable and very useful instrument for adapting, through the urea
      kinetic mathematical models, the dialysis dose for individual patients.

PMID- 9622114
TI  - Measurement of the upper limit of vulnerability during defibrillator implantation
      can substitute defibrillation threshold measurement.
AB  - We investigated whether defibrillation thresholds (DFTs) could be measured more
      safely during defibrillator implantation by measuring the upper limit of
      vulnerability (ULV) without using any special equipment. Nonthoracotomy ICD
      implantation with endocardial leads was performed in 13 patients, and through the
      use of the ICD function itself, ULV and DFT were measured using the delayed four
      episode up-down algorithm. Myocardial injures caused by high-energy current were
      assessed by electrocardiograms and serial CPK-MB. ULV was confirmed in all cases,
      and it strongly correlated with DFT. The average ULV was 5.9 +/- 3.3 J, while the
      average DFT was 7.9 +/- 4.3 J (r = 0.89, p < 0.0001, DFT = 1.20+1.14x ULV). The
      average ULV was thus significantly lower (p < 0.01). Although six patients were
      on amiodarone therapy, the strong correlation between ULV and DFT was also
      maintained (r = 0.97), p < 0.01) in these patients. In all cases, the CPK-MB
      failed to increase, and no myocardial injuries were detectable on
      electrocardiograms. We confirmed that ULV could be easily and safety measured
      during ICD implantation, and that ULV could be used instead of DFT.

PMID- 9622115
TI  - Optimisation of a stentless valve prosthesis based on an analytic parametric
      model of the aortic valve.
AB  - An analytical mathematical model of a stentless aortic valve has been
      implemented. The valve is characterised by a trileaflet geometry, cylindrical
      leaflets; the aortic root is schematised by a conical surface which includes the
      leaflet attachments. The model is defined through six geometric parameters: the
      base radius, the valve height, the commissure radius, the leaflet radial,
      circumferential and attachment line lengths. Five performance indexes have been
      used to optimise the valve geometry, namely: the systolic area, the leaflet
      circumferential stress in diastole, the leaflet bending strain in systole and two
      bending angles related to the rotation of the leaflets from the diastolic to the
      systolic configuration. The sensitivity analysis is carried out which can
      identify the influence of each geometric parameter on the performance indexes
      adopted for the optimum valve design. The analysis of the results provides the
      geometric configuration which optimises the overall function of the valve
      throughout the cardiac cycle.

PMID- 9622116
TI  - Intensive predeposit-hemodilution autologous blood donation and IOBS increase in
      erythropoietic levels in patients undergoing hip arthroplasty.
AB  - Erythropoietin (EPO) plasma levels were monitored during the perioperative period
      in 61 consecutive patients (22 males - 39 females), aged 62.5 +/- 9.5 years,
      scheduled for hip arthroplasty. All patients underwent intraoperative blood
      salvage (IOBS) and were subdivided into three different groups according to their
      hemoglobin levels (Hb) 24 hours postoperatively (group A: Hb < 8 g/dl; group B:
      Hb between 8-9 g/dl; group C: HB > or = 9 g/dl). Seventy-two hours after surgery
      EPO levels were significantly different in group A (135 +/- 68) compared to group
      C (54.3 +/- 32), with a positive correlation (p < 0.01) between Hb and EPO
      levels. On the basis of these results we suggest that a programmed autologous red
      blood cell collection aimed at obtaining the lowest hemoglobin values during the
      first 24 hours after surgery, may be of clinical utility in preventing homologous
      blood needs.

PMID- 9622117
TI  - pO2 measurement in an experimental model of patellar tendon autograft pro
      anterior cruciate ligament.
AB  - Thirty-four sheep were submitted to surgery substituting the native ACL with the
      central third of the patellar tendon, ten enter this study. The purpose was to
      find a possible relationship between tissue pO2 and healing processes considering
      also the biomechanical and histomorphological aspects of the grafts. Four of them
      were sacrificed under general anaesthesia after 6 months, and six after 1 year in
      order to perform tissue pO2 measurement and an analysis of microvessel density on
      specimens of the normal ACL and the graft. Our data showed higher pO2 values of
      the autografts after 6 months. After 1 year the data was comparable to those of
      native ACL. This was confirmed by a microvessel count of the histological
      specimens and the data was in relationship to biomechanical and
      histomorphological analysis. Tissue pO2 can be observed and recorded in "in vivo"
      ACL, and patellar tendon used as graft, with no injury to their integrity. The
      monitoring system might be considered as an experimental tool for indirect
      controls of the anterior cruciate substitutes.

PMID- 9622118
TI  - Influence of membrane oxygenators on the pulsatile flow in extracorporeal
      circuits: an experimental analysis.

PMID- 9622119
TI  - Urea-nitrogen concentration in blood.

PMID- 9622120
TI  - Effects of 3'-terminal phosphates in RNA produced by ribozyme cleavage.

PMID- 9622121
TI  - The use of antibodies to the polypyrimidine tract binding protein (PTB) to
      analyze the protein components that assemble on alternatively spliced pre-mRNAs
      that use distant branch points.
AB  - We are using the rat beta-tropomyosin (beta-TM) gene as a model system to study
      the mechanism of alternative splicing. Previous studies demonstrated that the use
      of the muscle-specific exon is associated with the use of distant branch points
      located 147-153 nt upstream of the 3' splice site. In addition, at least one
      protein, the polypyrimidine tract binding protein (PTB), specifically interacts
      with critical cis-acting sequences upstream of exon 7 that are involved in
      blocking the use of this alternative exon in nonmuscle cells. In order to further
      study the role of PTB, monoclonal antibodies to PTB were prepared. Anti-PTB
      antibodies did not inhibit the binding of PTB to RNA because they were able to
      supershift RNA-PTB complexes. To determine if additional proteins interact with
      sequences within the pre-mRNA, 35S-met-labeled nuclear extracts from HeLa cells
      were mixed with RNAs and the RNA-protein complexes were recovered by
      immunoprecipitation using antibodies to PTB. When RNAs containing intron 6 were
      added to an 35S-met-labeled nuclear extract, precipitation with PTB antibodies
      showed a novel set of proteins. By contrast, addition of RNAs containing introns
      5 or 7 gave the same results as no RNA, indicating that these RNAs are unable to
      form stable complexes with PTB. These results are in agreement with our previous
      studies demonstrating that PTB interacts with sequences within intron 6, but not
      with sequences within introns 5 and 7. When 35S-met-labeled HeLa nuclear extracts
      were mixed with biotinylated RNA containing intron 6 and the RNA-protein
      complexes were recovered using streptavidin-agarose beads, an identical pattern
      of proteins was observed when compared with the immunoprecipitation assay.
      Analysis of the proteins that assembled on introns 5, 6, or 7 using biotinylated
      RNA revealed a unique set of proteins that interact with each of these sequences.
      The composition of proteins interacting with sequences associated with the use of
      the 3' splice site of intron 6 included proteins of 30, 40, 55, 60, 65, 70, 80,
      and 100 kDa. Microsequencing identified two of the proteins to be Sam68 and the
      Far Upstream Element Binding Protein (FBP) from the c-myc gene. In addition, a
      comparison of the proteins that assemble on introns from the alpha- and beta-TM
      genes that utilize distant branch points revealed common as well as unique
      proteins that assemble on these introns. These studies identify a set of
      proteins, in addition to PTB, that are likely involved in the use of distant
      branch sites associated with the use of alternatively spliced introns.

PMID- 9622122
TI  - The polypyrimidine tract binding protein (PTB) requirement for internal
      initiation of translation of cardiovirus RNAs is conditional rather than
      absolute.
AB  - Picornavirus RNAs are translated by an unusual mechanism of internal ribosome
      entry that requires a substantial segment of the viral 5'-untranslated region,
      generally known as the internal ribosome entry segment (IRES), and in some
      circumstances may require cellular trans-acting proteins, particularly
      polypyrimidine tract binding protein (PTB). It is shown here that for
      encephalomyocarditis virus (EMCV), the PTB dependence of IRES function in vitro
      is determined partly by the nature of the reporter cistron, and more especially
      by the size of an A-rich bulge in the IRES. With a wild-type EMCV IRES (which has
      a bulge of 6 As), translation is effectively independent of PTB provided the IRES
      is driving the synthesis of EMCV viral polyprotein. With an enlarged (7A) bulge
      and heterologous reporters, translation is highly dependent on PTB. Intermediate
      levels of PTB dependence are seen with a 7A bulge IRES driving viral polyprotein
      synthesis or a wild-type (6A) bulge IRES linked to a heterologous reporter. None
      of these parameters influenced the binding of PTB to the high-affinity site in
      the IRES. These results argue that PTB is not an essential and universal internal
      initiation factor, but, rather, that when it is required, its binding to the IRES
      helps to maintain the appropriate higher-order structure and to reverse
      distortions caused, for example, by an enlarged A-rich bulge.

PMID- 9622123
TI  - Recognition of the universally conserved 3'-CCA end of tRNA by elongation factor
      EF-Tu.
AB  - Escherichia coli tRNA(Val) with pyrimidine substitutions for the universally
      conserved 3'-terminal adenine can be readily aminoacylated. It cannot, however,
      transfer valine into polypeptides. Conversely, despite being a poor substrate for
      valyl-tRNA synthetase, tRNA(Val) with a 3'-terminal guanine is active in in vitro
      polypeptide synthesis. To better understand the function of the 3'-CCA sequence
      of tRNA in protein synthesis, the effects of systematically varying all three
      bases on formation of the Val-tRNA(Val):EF-Tu:GTP ternary complex were
      investigated. Substitutions at C74 and C75 have no significant effect, but
      replacing A76 with pyrimidines decreases the affinity of valyl-tRNA(Val) for EF
      Tu:GTP, thus explaining the inability of these tRNA(Val) variants to function in
      polypeptide synthesis. Valyl-tRNA(Val) terminating in 3'-guanine is readily
      recognized by EF-TU:GTP. Dissociation constants of the EF-Tu:GTP ternary
      complexes with valine tRNAs having nucleotide substitutions at the 3' end
      increase in the order adenine < guanine < uracil; EF-Tu has very little affinity
      for tRNA terminating in 3' cytosine. Similar observations were made in studies of
      the interaction of 3' end mutants of E. coli tRNA(Ala) and tRNA(Phe) with EF
      Tu:GTP. These results indicate that EF-Tu:GTP preferentially recognizes purines
      and discriminates against pyrimidines, especially cytosine, at the 3' end of
      aminoacyl-tRNAs.

PMID- 9622124
TI  - The RNA sequence context defines the mechanistic routes by which yeast arginyl
      tRNA synthetase charges tRNA.
AB  - Arginylation of tRNA transcripts by yeast arginyl-tRNA synthetase can be
      triggered by two alternate recognition sets in anticodon loops: C35 and U36 or
      G36 in tRNA(Arg) and C36 and G37 in tRNA(Asp) (Sissler M, Giege R, Florentz C,
      1996, EMBO J 15:5069-5076). Kinetic studies on tRNA variants were done to explore
      the mechanisms by which these sets are expressed. Although the synthetase
      interacts in a similar manner with tRNA(Arg) and tRNA(Asp), the details of the
      interaction patterns are idiosyncratic, especially in anticodon loops (Sissler M,
      Eriani G, Martin F, Giege R, Florentz C, 1997, Nucleic Acids Res 25:4899-4906).
      Exchange of individual recognition elements between arginine and aspartate tRNA
      frameworks strongly blocks arginylation of the mutated tRNAs, whereas full
      exchange of the recognition sets leads to efficient arginine acceptance of the
      transplanted tRNAs. Unpredictably, the similar catalytic efficiencies of native
      and transplanted tRNAs originate from different k(cat) and Km combinations. A
      closer analysis reveals that efficient arginylation results from strong
      anticooperative effects between individual recognition elements. Nonrecognition
      nucleotides as well as the tRNA architecture are additional factors that tune
      efficiency. Altogether, arginyl-tRNA synthetase is able to utilize different
      context-dependent mechanistic routes to be activated. This confers biological
      advantages to the arginine aminoacylation system and sheds light on its
      evolutionary relationship with the aspartate system.

PMID- 9622125
TI  - New features of 23S ribosomal RNA folding: the long helix 41-42 makes a "U-turn"
      inside the ribosome.
AB  - 23S rRNA from Escherichia coli was cleaved at single internucleotide bonds using
      ribonuclease H in the presence of appropriate chimeric oligonucleotides; the
      individual cleavage sites were between residues 384 and 385, 867 and 868, 1045
      and 1046, and 2510 and 2511, with an additional fortuitous cleavage at positions
      1117 and 1118. In each case, the 3' terminus of the 5' fragment was ligated to
      radioactively labeled 4-thiouridine 5'-,3'-biphosphate ("psUp"), and the cleaved
      23S rRNA carrying this label was reconstituted into 50S subunits. The 50S
      subunits were able to associate normally with 30S subunits to form 70S ribosomes.
      Intra-RNA crosslinks from the 4-thiouridine residues were induced by irradiation
      at 350 nm, and the crosslink sites within the 23S rRNA were analyzed. The rRNA
      molecules carrying psUp at positions 867 and 1117 showed crosslinks to nearby
      positions on the opposite strand of the same double helix where the cleavage was
      located, and no crosslinking was detected from position 2510. In contrast, the
      rRNA carrying psUp at position 384 showed crosslinking to nt 420 (and sometimes
      also to 416 and 425) in the neighboring helix in 23S rRNA, and the rRNA with psUp
      at position 1045 gave a crosslink to residue 993. The latter crosslink
      demonstrates that the long helix 41-42 of the 23S rRNA (which carries the region
      associated with GTPase activity) must double back on itself, forming a "U-turn"
      in the ribosome. This result is discussed in terms of the topography of the
      GTPase region in the 50S subunit, and its relation to the locations of the 5S
      rRNA and the peptidyl transferase center.

PMID- 9622126
TI  - Using reliability information to annotate RNA secondary structures.
AB  - A number of heuristic descriptors have been developed previously in conjunction
      with the mfold package that describe the propensity of individual bases to
      participate in base pairs and whether or not a predicted helix is "well
      determined." They were developed for the "energy dot plot" output of mfold. Two
      descriptors, P-num and H-num, are used to measure the level of promiscuity in the
      association of any given nucleotide or helix with alternative complementary
      pairs. The third descriptor, S-num, measures the propensity of bases to be single
      stranded. In the current work, we describe a series of programs that were
      developed in order to annotate individual structures with "well-definedness"
      information. We use color annotation to present the information. The programs can
      annotate PostScript files that are created by the mfold package or the PostScript
      secondary structure plots produced by the Weiser and Noller program XRNA (Weiser
      B, Noller HF, 1995, XRNA: Auto-interactive program for modeling RNA, The Center
      for Molecular Biology of RNA, Santa Cruz, California: University of California;
      Internet: ftp://fangio.ucsc.edu/pub/XRNA). In addition, these programs can
      annotate ss files that serve as input to XRNA. The annotation package can also
      handle structure comparison with a reference structure. This feature can be used
      to compare predicted structure with a phylogenetically deduced model, to compare
      two different predicted foldings, and to identify conformational changes that are
      predicted between wild-type and mutant RNAs. We provide several examples of
      application. Predicted structures of two RNase P RNAs were colored with P-num
      information and further annotated with comparative information. The comparative
      model of a 16S rRNA was annotated with P-num information from mfold and with base
      pair probabilities obtained from the Vienna RNA folding package. Further
      annotation adds comparisons with the optimal foldings obtained from mfold and the
      Vienna package, respectively. The results of all of these analyses are discussed
      in the context of the reliability of structure prediction.

PMID- 9622128
TI  - Influence of substrate structure on in vitro ribozyme activity of a group II
      intron.
AB  - Substrate sequences surrounding catalytic RNAs but not involved in specific,
      conserved interactions can severely interfere with in vitro ribozyme activity.
      Using model group II intron precursor transcripts with truncated or randomized
      exon sequences, we show that unspecific sequences within the 5' exon are
      particularly prone to inhibit both the forward and the reverse first splicing
      step (branching). Using in vitro selection, we selected efficient 5' exons for
      the reverse branching reaction. Precursor RNAs carrying these selected 5' exons
      reacted more homogeneously and faster than usual model precursor transcripts.
      This suggests that unfavorable structures induced by the 5' exon can introduce a
      folding step that limits the rate of in vitro self-splicing. These results stress
      how critical is the choice of the sequences retained or discarded when isolating
      folding domains from their natural sequence environments. Moreover, they suggest
      that exon sequences not involved in specific interactions are more evolutionarily
      constrained with respect to splicing than previously envisioned.

PMID- 9622127
TI  - Localization of hepatitis delta virus RNA in the nucleus of human cells.
AB  - Hepatitis delta virus (HDV) is a human pathogen that can greatly increase the
      severity of liver damage caused by an hepatitis B infection. HDV contains a
      circular, single-stranded RNA genome that encodes a unique protein, the delta
      antigen. Two forms of the delta antigen, deltaAg-S and deltaAg-L, are derived
      from a single open reading frame by RNA editing. Here we analyze the subcellular
      distribution of HDV RNA and its spatial relationship to known intranuclear
      structures. The human hepatoma cell line Huh7 was stably transfected with wild
      type HDV cDNA and the viral RNAs were localized by in situ hybridization and
      fluorescence confocal microscopy. HDV RNA is detected throughout the nucleoplasm,
      with additional concentration in focal structures closely associated with nuclear
      speckles or clusters of interchromatin granules. Both the smaller form of the
      delta antigen (deltaAg-S), which is required for HDV genomic replication, and the
      larger form of the delta antigen (deltaAg-L), which represses replication, co
      localize with delta RNA throughout the nucleoplasm and in the foci. However, the
      foci do not incorporate bromo-UTP and do not concentrate either RNA polymerase II
      or cleavage and polyadenylation factors required for viral RNA synthesis and 3'
      end processing, respectively. Thus, it is unlikely that the delta foci represent
      major sites of viral transcription or replication. In conclusion, the data show
      that viral RNA-protein complexes accumulate in structures closely associated with
      interchromatin granules, a subnuclear domain highly enriched in small nuclear
      ribonucleoproteins, poly(A+) RNA, and RNA splicing protein factors. This implies
      a specific compartmentalization of ribonucleoproteins in the nucleus.

PMID- 9622129
TI  - Base pairing with U6atac snRNA is required for 5' splice site activation of U12
      dependent introns in vivo.
AB  - The minor U12-dependent class of eukaryotic nuclear pre-mRNA introns is spliced
      by a distinct spliceosomal mechanism that requires the function of U11, U12, U5,
      U4atac, and U6atac snRNAs. Previous work has shown that U11 snRNA plays a role
      similar to U1 snRNA in the major class spliceosome by base pairing to the
      conserved 5' splice site sequence. Here we show that U6atac snRNA also base pairs
      to the 5' splice site in a manner analogous to that of U6 snRNA in the major
      class spliceosome. We show that splicing defective mutants of the 5' splice site
      can be activated for splicing in vivo by the coexpression of compensatory U6atac
      snRNA mutants. In some cases, maximal restoration of splicing required the
      coexpression of compensatory U11 snRNA mutants. The allelic specificity of mutant
      phenotype suppression is consistent with Watson-Crick base pairing between the
      pre-mRNA and the snRNAs. These results provide support for a model of the RNA-RNA
      interactions at the core of the U12-dependent spliceosome that is strikingly
      similar to that of the major class U2-dependent spliceosome.

PMID- 9622130
TI  - Global structure of four-way RNA junctions studied using fluorescence resonance
      energy transfer.
AB  - Four-way helical junctions are found widely in natural RNA species. In this
      study, we have studied the conformation of two junctions by fluorescence
      resonance energy transfer. We show that the junctions are folded by pairwise
      coaxial helical stacking, forming one predominant stacking conformer in both
      examples studied. At low magnesium ion concentrations, the helical axes of both
      junctions are approximately perpendicular. One junction undergoes a rotation into
      a distorted antiparallel structure induced by the binding of a single magnesium
      ion. By contrast, the axes of the four-way junction of the U1 snRNA remain
      approximately perpendicular under all conditions examined, and we have determined
      the stacking conformer adopted.

PMID- 9622131
TI  - Conference report on stroke mortality in the southeastern United States.
AB  - A workshop to describe and then seek possible causes for the increased stroke
      mortality in the southeastern United States briefly considered 30 suspected
      correlates and discussed in more detail the 10 thought to be most likely. Recent
      age-adjusted stroke mortality rates in adults from industrialized countries
      reveal marked geographic differences. Age-adjusted statewide stroke mortality
      rates also differ, and they are higher in the Southeast than elsewhere in the
      United States. For five southeastern coastal states in the heart of the "Stroke
      Belt," excess stroke mortality has been present at least since 1930. In a 20-year
      follow-up of 10,000 veterans, the Stroke Belt had a 25% increase in all-cause
      mortality and congestive heart failure. A potential cause of increased fatal
      stroke included hypertension, which was more frequent in the Stroke Belt. No
      consistent patterns of lifestyle differences or of differences in potassium or
      calcium intake seemed to explain the higher rates of fatal strokes in the Stroke
      Belt; however, detailed investigations of smaller populations in localized areas
      seem warranted. Some data suggest a relationship between socioeconomic status and
      the Stroke Belt effect. Other differences in the Southeast that could explain, at
      least partially, the Stroke Belt effect include presence of soft water throughout
      most of the area, decreased antioxidant intake, and differences in the use of
      medical care and in the response to antihypertensive drugs. On the basis of
      available information, the three most likely explanations or partial explanations
      for the Stroke Belt are increased levels of blood pressure, localized differences
      in socioeconomic status, and toxic environmental factor(s). Two major
      recommendations were made: (1) to encourage both patient and caregiver to use all
      currently available means of decreasing morbidity and mortality by controlling
      blood pressures at or below normal levels and by reducing other risk factors and
      (2) to seek precise information about relationships of identified possible causes
      of increased morbidity and mortality in the Stroke Belt.

PMID- 9622132
TI  - Cerebral blood flow in hypertensive patients: an initial report of reduced and
      compensatory blood flow responses during performance of two cognitive tasks.
AB  - We asked whether the altered cerebral vasculature associated with essential
      hypertension might dampen or redirect the regional cerebral blood flow (rCBF)
      response to cognitive work. Relative rCBF was assessed with [(15)O]water positron
      emission tomography during a working memory task, a memory span task, and two
      perceptual control tasks. Unmedicated hypertensive patients and control subjects
      differed in rCBF response during both memory tasks. Hypertensives showed
      relatively diminished rCBF responses in right hemisphere areas combined with
      compensatory activation of homologous areas in the left cerebral cortex.
      Essential hypertension appears to selectively influence the circulatory reserve
      of portions of cerebral cortex and secondarily induce recruitment of other
      cortical areas to process certain tasks.

PMID- 9622133
TI  - Three important subgroups of hypertensive persons at greater risk of
      intracerebral hemorrhage. Melbourne Risk Factor Study Group.
AB  - Hypertension as a risk factor for intracerebral hemorrhage (ICH) is poorly
      quantified, particularly in the setting of the use of modern antihypertensive
      agents. To investigate this, we studied 331 consecutive hospital cases of primary
      ICH verified by computed tomography or autopsy, occurring during the period 1990
      through 1992, and 331 age- and sex-matched community-based control subjects in a
      city-wide study involving 13 hospitals. Hypertension approximately doubled the
      risk of ICH (adjusted odds ratio [OR], 2.45; 95% confidence interval [CI], 1.61
      to 3.73). The OR associated with hypertension was significantly greater among
      those who had ceased taking medications, supervised and unsupervised (OR, 4.98;
      95% CI, 2.25 to 11.02), compared with those who had not (OR, 1.95; 95% CI, 1.20
      to 3.16), were under the age of 55 years (OR, 7.68; 95% CI, 2.65 to 22.5), or
      were current smokers (OR, 6.12; 95% CI, 2.29 to 16.35). The presence of
      hypertension did not influence size or location of the hemorrhage. However, those
      dying from ICH displayed a greater risk of ICH due to hypertension than
      survivors, with the ratio of the two ORs being 5.47 (95% CI, 1.23 to 24.44).
      These findings provide evidence for a greater increase in risk of ICH due to
      hypertension among younger persons, current smokers, and those discontinuing
      antihypertensive therapy. This is the first direct evidence for a link between
      stopping antihypertensive medication use and stroke risk; targeting these
      individuals for more intensive monitoring and education on the importance of risk
      factor modification may help to reduce the impact of this form of stroke.

PMID- 9622134
TI  - Genetic markers at the leptin (OB) locus are not significantly linked to
      hypertension in African Americans.
AB  - Increased body mass index (BMI) has been correlated with increased blood pressure
      in human populations. To examine the role of the leptin gene (OB) in essential
      hypertension in African Americans, we performed affected sib pair analysis on a
      set of 103 hypertensive African American sibships using four highly polymorphic
      markers at the human leptin locus. No evidence of linkage was detected between
      these markers and the phenotype of essential hypertension either in these
      sibships or in a severely obese subset of 46 sibships in which each sibling had a
      BMI > or = 85th percentile for the US population. Using BMI rather than
      hypertension as a quantitative trait, we found significant linkage for the marker
      D7S504 (P=0.029) but not for the other markers. Significance strengthened in the
      overweight subset of sibships for this marker (P=0.001), and there was a trend of
      lower P values for the other three markers. However, multipoint analysis with the
      use of all four markers simultaneously to estimate linkage between BMI and the
      leptin locus did not demonstrate a statistically significant relationship.
      Analysis of the coding region of the leptin gene (exons 2 and 3) by single-strand
      conformational polymorphism revealed a rare Ile-Val polymorphism at amino acid 45
      but revealed no other alterations. These results suggest that the OB gene is not
      a major contributor to the phenotype of essential hypertension in African
      Americans, although a minor contribution to the phenotype of extreme obesity in
      this group cannot be ruled out.

PMID- 9622135
TI  - Racial differences in nitric oxide-mediated vasodilator response to mental stress
      in the forearm circulation.
AB  - An abnormal hemodynamic response to stressful stimuli has been proposed as a
      mechanism involved in the higher prevalence of hypertension in blacks. Given the
      important role of nitric oxide (NO) in the regulation of cardiovascular
      homeostasis, we investigated the possibility of racial differences in vascular NO
      activity during mental stress. To test this hypothesis, we compared the forearm
      blood flow (FBF) response to mental stress in 14 white and 12 black healthy
      subjects during intra-arterial infusion of either saline or NO synthesis
      inhibitor N(G)-monomethyl-L-arginine (L-NMMA; 4 micromol/min). We also examined
      vascular responses of the two groups to intra-arterial infusion of sodium
      nitroprusside (0.8 to 3.2 microg/min), an exogenous NO donor. During saline
      infusion, the increase in FBF from baseline induced by mental stress was
      significantly higher in whites than in blacks (109+/-20% versus 58+/-8%; P=0.03).
      L-NMMA significantly reduced stress-induced increase in FBF in whites (from 109+/
      20% to 54+/-11%; P=0.004) but not in blacks (from 58+/-8% to 42+/-10%; P=0.24);
      thus, the vasodilator effect of stress testing during L-NMMA was similar in
      whites and blacks (54+/-11% versus 42+/-10%; P=0.44). The vasodilator response to
      sodium nitroprusside was also lower in blacks than in whites (maximum flow, 6.9+/
      2 versus 11.6+/-3.5 mL x min(-1) x dL(-1); P=0.001) and was not significantly
      modified by L-NMMA in either group. Our findings indicate that blacks have a
      reduced NO-dependent vasodilator activity during mental stress. This difference
      seems related to reduced sensitivity of smooth muscle to the vasodilator effect
      of NO and may play some role in the increased prevalence of hypertension and its
      complications in blacks.

PMID- 9622136
TI  - Relaxin activates the L-arginine-nitric oxide pathway in vascular smooth muscle
      cells in culture.
AB  - The peptide hormone relaxin (RLX) has been shown to elicit a powerful
      vasodilatory response in several target organs. This response is mediated by the
      stimulation of intrinsic nitric oxide (NO) generation. The present study was
      designed to clarify whether RLX directly promotes the relaxation of vascular
      smooth muscle cells through stimulation of NO generation. Vascular smooth muscle
      cells from bovine aortas were incubated with RLX at concentrations ranging from 1
      nmol/L to 1 micromol/L. The expression and activity of NO synthase, production of
      NO, and the intracellular levels of cGMP and Ca2+ were determined. The cell
      morphology and signal transduction mechanisms of these bovine aortic smooth
      muscle cells in response to RLX were also studied. RLX stimulated the expression
      of immunoreactive inducible NO synthase and increased significantly and in a
      concentration-related fashion inducible NO synthase activity, NO generation, and
      intracellular cGMP levels. Concurrently, RLX significantly decreased cytosolic
      Ca2+ concentrations and caused changes in cell shape and the actin cytoskeleton
      that were consistent with cell relaxation. The signal transduction mechanisms
      leading to the enhanced expression of inducible NO synthase protein and activity
      caused by RLX involve the activation of tyrosine kinase, phosphatidylcholine
      phospholipase C, and the transcription factor nuclear factor-kappaB, similar to
      bacterial endotoxins and proinflammatory cytokines. This study suggests that RLX
      is an endogenous agent capable of regulating vascular tone by activation of the L
      arginine-NO pathway in vascular smooth muscle cells.

PMID- 9622137
TI  - Upregulation of renal and vascular nitric oxide synthase in young spontaneously
      hypertensive rats.
AB  - The available data on the role of the L-arginine/nitric oxide (NO) pathway in the
      genesis of hypertension in spontaneously hypertensive rats (SHR) are limited and
      contradictory. In an attempt to address this issue, male SHR were studied during
      the early phase of evolution of hypertension (age 8 to 12 weeks) to distinguish
      the primary changes of NO metabolism from those caused by advanced hypertension,
      vasculopathy, and aging late in the course of the disease. A group of age-matched
      male Wistar-Kyoto rats (WKY) served as controls. The SHR exhibited a marked rise
      in arterial blood pressure and a significant increase in urinary excretion and
      plasma concentration of NO metabolites (nitrite/nitrate [NOx]). Likewise, the SHR
      showed a significant elevation of thoracic aorta NO synthase (NOS) activity
      coupled with significant increases of kidney, aorta, inducible NOS (iNOS), and
      endothelial NOS (eNOS) proteins. In an attempt to determine whether the enhanced
      L-arginine/NO pathway is a consequence of hypertension, studies were repeated
      using 3-week-old animals before the onset of hypertension. The study revealed
      significant increases in urinary NOx excretion as well as vascular eNOS and renal
      iNOS proteins. In conclusion, the L-arginine/NO pathway is upregulated in young
      SHR both before and after the onset of hypertension. Thus, development of
      hypertension is not due to a primary impairment of NO production in SHR. On the
      contrary, NO production is increased in young SHR both before and after the onset
      of hypertension.

PMID- 9622138
TI  - Interactive nitric oxide-angiotensin II influences on renal microcirculation in
      angiotensin II-induced hypertension.
AB  - The present study was conducted to determine the contribution of nitric oxide to
      angiotensin II (Ang II) reactivity of afferent and efferent arterioles from Ang
      II-infused hypertensive rats. Experiments were performed in vitro with the blood
      perfused juxtamedullary nephron technique in kidneys harvested from hypertensive
      Sprague-Dawley rats (181+/-1 mm Hg) that had received 60 ng/min Ang II
      subcutaneously for 13 days. Superfusion with 0.1, 1, and 10 nmol/L Ang II reduced
      afferent arteriolar diameter (18.1+/-0.6 microm; n=12) by 10.0+/-0.7%, 28.1+/
      1.7%, and 52.8+/-1.9%, respectively, and efferent arteriolar diameter (17.2+/-1.4
      microm; n=8) decreased by 9.3+/-0.7%, 27.0+/-1.2%, and 50.4+/-1.6%, respectively.
      Nitric oxide synthase inhibition with 100 micromol/L N(omega)-nitro-L-arginine
      (NLA) reduced resting afferent and efferent arteriolar diameters to 14.7+/-0.4
      and 14.3+/-1.2 microm, respectively, and enhanced afferent but not efferent
      arteriolar reactivity to Ang II. The enhanced afferent arteriolar reactivity to
      Ang II was eliminated by addition of the nitric oxide donor S-nitroso-N
      acetylpenicillamine (SNAP, 10 micromol/L), which reversed the NLA-induced
      decrease in diameter. Addition of 10 micromol/L SNAP, without NLA, blunted
      efferent but not afferent arteriolar reactivity to Ang II. Afferent (n=7) and
      efferent arteriolar diameters (n=6) decreased by 48.5+/-2.2% and 41.0+/-1.9%,
      respectively, in response to 10 nmol/L Ang II. These results suggest that in this
      model of hypertension, maintained nitric oxide production in afferent arterioles
      counteracts the enhanced afferent arteriolar reactivity that occurs in Ang II
      induced hypertension.

PMID- 9622139
TI  - Dietary sodium restriction impairs endothelial effect of insulin.
AB  - Hyperinsulinemia and high salt intake represent two independent cardiovascular
      risk factors. However, it is still unknown whether the change in dietary salt
      intake may affect the ability of insulin to stimulate whole-body glucose uptake
      and to modulate endothelial function. Regarding this latter issue, we have
      recently demonstrated that insulin enhances endothelial-mediated alpha2
      adrenergic vasorelaxation. In overnight-fasted, freely moving Wistar-Kyoto rats
      (10 to 12 weeks old), we assessed whole-body glucose uptake (in milligrams per
      kilogram per minute) during a euglycemic-hyperinsulinemic clamp (insulin infusion
      rate, 3 mU x kg(-1) x min(-1)) after 3 weeks of normal (NSD, 2% NaCl), high (HSD,
      6% NaCl), and low (LSD, 0.6% NaCl) sodium diet. Three days after the clamp study,
      rats were killed to assess alpha2-adrenergic vasorelaxation evoked by UK 14,304
      (10(-9) to 10(-6) mol/L) in aortic rings in control conditions and after insulin
      exposure (100 microU/mL). Different sodium intakes did not modify the mean blood
      pressure or the insulin-stimulated whole-body glucose uptake (NSD: 14+/-1.2,
      n=16; HSD: 15.4+/-1.7, n=14; LSD: 14.8+/-0.8, n=14; NS). In contrast, we
      confirmed the ability of insulin to enhance alpha2-adrenergic vasorelaxation
      during NSD and HSD (delta% of maximal relaxation, NSD: from 32+/-3% to 58+/-3.4%,
      n=9, P<0.01; HSD: from 33+/-3.8% to 59+/-3.5%, n=8, P<0.01), but this effect was
      impaired during LSD (delta% maximal relaxation, from 36+/-1.5% to 36+/-3.4%, n=8,
      NS). In conclusion, our data demonstrate that in Wistar-Kyoto rats, changes in
      dietary salt intake do not modify the insulin-stimulated whole-body glucose
      uptake. In contrast, LSD impairs the insulin potentiation of alpha2-adrenergic
      vasorelaxation, thus suggesting that dietary salt restriction provokes an
      impairment of insulin effect on endothelial function.

PMID- 9622140
TI  - Insulin-mediated venodilation is impaired in patients with high cholesterol.
AB  - Recently we have reported that insulin attenuates norepinephrine (NE)-induced
      vasoconstriction via a cyclic GMP-NO synthase pathway. Because
      hypercholesterolemia has been associated with abnormal endothelial function, we
      investigated whether insulin-mediated vasodilation is impaired in
      hypercholesterolemia. To assess vasoreactivity, NE (12.5, 25, 50, and 100
      ng/min), NE (100 ng/min) combined with insulin (8, 16, 24, and 32 microU/min),
      and NE (100 ng/min) combined with sodium nitroprusside (0.01, 0.1, 1, 10, and 100
      ng/min) were infused into dorsal hand veins. Changes in venous diameter were
      measured by ultrasonography, using a 7.5-MHz transducer. Twenty-two healthy,
      normotensive hypercholesterolemic subjects (HC; mean total cholesterol 6.93
      mmol/L, HDL 1.45 mmol/L, LDL 4.81 mmol/L) and 18 age-matched normal control
      subjects (NC; mean total cholesterol 4.81 mmol/L, HDL 1.16 mmol/L, LDL 3.18
      mmol/L) were studied. All HC had normal glucose tolerance test results. Baseline
      vein diameters were similar between groups, and the vasoconstrictor response to
      NE was not significantly different between HC and NC. Insulin significantly
      attenuated NE-induced vasoconstriction in NC but not in HC (P<0.01). Both groups
      were able to venodilate with sodium nitroprusside. To investigate the effects of
      cholesterol reduction on vascular reactivity, venoreactivity studies were
      repeated in 12 HC after treatment with 20 to 40 mg/d lovastatin for 6 weeks.
      There were no significant venoreactivity changes with the treatment. Plasma LDL
      cholesterol concentration was inversely correlated to venodilator effect of
      insulin (r=-0.42, P<0.02). In conclusion, insulin-mediated vasodilation is
      impaired in patients with high cholesterol. Absence of normal insulin-mediated
      but not sodium nitroprusside-induced venodilation in hypercholesterolemia
      suggests that insulin-mediated vasodilation is endothelium dependent.

PMID- 9622141
TI  - Salt induces vascular AT1 receptor overexpression in vitro and in vivo.
AB  - The molecular events governing salt-sensitive hypertension are currently unknown.
      Because the renin-angiotensin system plays a central role in blood pressure
      regulation, as well as electrolyte balance, it may be closely involved in the
      phenomenon of salt sensitivity. Therefore, we examined the effect of a high salt
      diet (8%) on aortic angiotensin type 1 (AT1) receptor expression in Sprague
      Dawley rats by means of radioligand binding assays and quantitative polymerase
      chain reaction. High salt intake caused an increase of AT1 receptor mRNA and AT1
      receptor density to approximately 160% compared with control levels. Northern
      analysis revealed that incubation of vascular smooth muscle cells (VSMCs) with an
      increased concentration of sodium chloride (by 10 mmol/L) caused a time-dependent
      elevation of AT1 receptor mRNA levels, with a maximum of 241+/-28% after 24
      hours. There was a similar increase in AT1 receptor density in VSMCs in response
      to sodium chloride, as assessed by radioligand binding assays. The salt-induced
      AT1 receptor upregulation led to an enhanced functional response of VSMCs on
      stimulation with angiotensin II, since the angiotensin II-elicited intracellular
      calcium response was significantly increased in cells preincubated for 24 hours
      with the high salt concentration. Thus, sodium chloride may directly induce AT1
      receptor upregulation in vitro as well as in vivo; this suggests a potential
      mechanism participating in salt-induced hypertension because the AT1 receptor
      activation is tightly coupled to blood pressure regulation.

PMID- 9622142
TI  - Enhanced blood pressure sensitivity to deoxycorticosterone in mice with
      disruption of bradykinin B2 receptor gene.
AB  - The renal kallikrein-kinin system is activated under conditions of
      mineralocorticoid excess. To evaluate whether endogenous kinins exert a
      protective role against the development of mineralocorticoid-induced
      hypertension, we studied the cardiovascular effects induced by long-term
      administration of deoxycorticosterone (DOC; 0.3 micromol/g body wt s.c. once per
      week for 6 weeks) or vehicle in transgenic mice (Bk2r-/-) lacking the bradykinin
      B2 receptor gene and in wild-type controls (Bk2r+/+). Under basal conditions,
      Bk2r-/- mice showed higher systolic blood pressure (tail-cuff plethysmography)
      than wild-type Bk2r+/+ and heterozygous Bk2r+/- mice (121+/-2 versus 114+/-2 and
      115+/-2 mm Hg, respectively; P<0.05 for both comparisons). Heart rate was higher
      in Bk2r-/- and Bk2r+/- than in Bk2r+/+ (459+/-12 and 418+/-7 versus 390+/-7 bpm;
      P<0.05 for both comparisons). Systolic blood pressure was increased by DOC in
      transgenic as well as in wild-type mice, whereas no change was induced by the
      vehicle. The pressor response to DOC was more rapid and pronounced in Bk2r-/-
      than in Bk2r+/+ and Bk2r+/- (30+/-5 versus 15+/-4 and 6+/-3 mm Hg, respectively,
      at 3 weeks; P<0.01 for both comparisons). The difference in systolic blood
      pressure was consistent with that detected by direct intra-arterial measurements
      of mean blood pressure. Neither DOC nor its vehicle altered heart rate or gain in
      body weight over time. Under basal conditions, urinary sodium excretion did not
      differ between strains. During DOC administration, cumulative urinary sodium
      excretion was lower in Bk2r-/- than in Bk2r+/+ (2.59+/-0.15 versus 3.31+/-0.22
      mmol, respectively, during the first week; P<0.05). Urinary kinin excretion was
      increased by DOC in both Bk2r-/- (from 0.65+/-0.17 to 4.27+/-0.80 pmol/24 h;
      P<0.01) and Bk2r+/+ (from 0.55+/-0.09 to 6.27+/-1.48 pmol/24 h; P<0.05). The
      increase in urinary kinin excretion was similar between strains. These results
      show that integrity of the bradykinin B2 receptor is essential for regulation of
      blood pressure and heart rate under basal conditions. In addition, they indicate
      that activation of the kallikrein-kinin system represents a compensatory response
      against the development of hypertension induced by mineralocorticoid excess.

PMID- 9622143
TI  - Red blood cell sodium-lithium countertransport and risk of future hypertension:
      the Olivetti Prospective Heart Study.
AB  - An elevated red blood cell (RBC) sodium-lithium countertransport (Na-Li CT) is
      associated with high blood pressure (BP) in cross-sectional investigations;
      however, its value as a predictor of future hypertension, and thus of
      cardiovascular risk, has not been defined. The present study evaluated the
      association between Na-Li CT and risk of future hypertension in a sample of 106
      untreated normotensive middle-aged men participating in the Olivetti Prospective
      Heart Study in southern Italy. BP, anthropometric and metabolic variables, and
      RBC Na-Li CT were measured at baseline in 1987 and at a follow-up visit in 1994
      through 1995. Na-Li CT was stable over time (r=0.85) and was significantly
      associated to systolic BP in both visits. Of the 106 initially normotensive
      participants, 14 were found to be hypertensive at the 8-year follow-up
      examination. Eleven of these 14 hypertensives were in the highest tertile of
      systolic BP at baseline, and 9 of 11 also had an elevated baseline Na-Li CT. In
      multiple logistic regression analysis, baseline BP, Na-Li CT, and age were all
      significant predictors of the risk of future hypertension. Individuals with
      baseline systolic BP in the highest tertile had a 60% risk of developing
      hypertension if their Na-Li CT was also high, whereas their risk was only 5% if
      Na-Li CT was in the two lowest tertiles (P=0.003). RBC Na-Li CT was a valuable
      predictor of subsequent hypertension in middle-aged men with a high-normal BP
      level for their age.

PMID- 9622144
TI  - Role of Ca2+-activated K+ channels in the protective effect of ACE inhibition
      against ischemic myocardial injury.
AB  - Angiotensin-converting enzyme (ACE) inhibitors increase the production of nitric
      oxide (NO) and prostacyclin and open Ca2+-activated K+ channels. The effects of
      these actions of ACE inhibitors on infarct size were investigated in open-chest
      dogs subjected to myocardial ischemia and reperfusion. Infarct size was assessed
      6 hours after the onset of reperfusion, subsequent to 90 minutes of occlusion of
      the left anterior descending coronary artery. The ACE inhibitor cilazaprilat was
      administered into the coronary artery 10 minutes before coronary occlusion, and
      infusion was continued until 1 hour after reperfusion. The bradykinin and NO
      concentrations in coronary venous blood 10 minutes after the onset of reperfusion
      were significantly higher in dogs treated with cilazaprilat (3 microg x kg(-1) x
      min(-1)) than in control animals. Although there were no significant differences
      in collateral flow during ischemia, infarct size in the cilazaprilat group was
      smaller than that in the control group (15.1+/-3.0% versus 46.7+/-4.2% of the
      area at risk, P<0.0001). The infarct size-limiting effect of cilazaprilat was
      partially reduced by either N(G)-nitro-L-arginine methyl ester (an inhibitor of
      NO synthase) or iberiotoxin (a blocker of Ca2+-activated K+ channels) and was
      abolished by N(G)-nitro-L-arginine methyl ester plus iberiotoxin. Indomethacin
      (an inhibitor of cyclooxygenase) had no effect on the beneficial action of
      cilazaprilat. Inhibition of ACE thus reduced myocardial infarct size, an effect
      that was mediated by NO and the opening of Ca2+-activated K+ channels in canine
      hearts.

PMID- 9622145
TI  - Acute ACE inhibition causes plasma extravasation in mice that is mediated by
      bradykinin and substance P.
AB  - The use of angiotensin-converting enzyme (ACE) has been associated with the
      occurrence of adverse effects, including cough and angioneurotic edema.
      Accumulation of kinins has been suggested to play a major role in these adverse
      effects of ACE inhibitor, although conclusive evidence for such a role is
      lacking. We investigated whether ACE inhibition increases plasma extravasation in
      mice (Swiss, C57Bl/6J, and J129Sv/Ev strains) via inhibition of bradykinin
      metabolism and stimulation of neurogenic inflammatory mechanisms. Intravenous
      captopril and enalapril increased the extravasation of Evans blue dye in all
      tissues examined (trachea, stomach, duodenum, and pancreas). This effect was
      evident 15 minutes after drug administration. The particulate dye Monastral blue
      identified the sites of captopril-induced leakage in the microvasculature.
      Pretreatment with the bradykinin B2 receptor antagonist Hoe 140 or with the
      tachykinin NK1 receptor antagonist SR 140333 inhibited captopril-evoked increase
      in plasma extravasation. In mice in which the gene encoding the bradykinin B2
      receptor was disrupted by gene targeting, neither bradykinin nor captopril
      increased plasma extravasation. Pretreatment with Hoe 140 did not reduce the
      hypotensive response induced by captopril. The present findings suggest that ACE
      inhibition increases kinin levels in tissues and/or plasma. These increased kinin
      levels increase microvascular leakage in mouse airways and digestive tract via
      the release of tachykinins from terminals of primary sensory neurons. Exaggerated
      kinin production and the subsequent stimulation of peptide release from sensory
      nerves may be involved in adverse effects of ACE inhibitors.

PMID- 9622146
TI  - Losartan but not verapamil inhibits angiotensin II-induced tissue endothelin-1
      increase: role of blood pressure and endothelial function.
AB  - Endothelin partially mediates angiotensin (Ang) II-induced vascular changes in
      vivo. This study investigated the effects of the angiotensin type 1 receptor
      antagonist losartan and the calcium channel blocker verapamil on vascular
      reactivity and tissue endothelin-1 levels in aortas of Wistar-Kyoto rats treated
      for 2 weeks with Ang II (200 ng x kg(-1) x min(-1)). Ang II increased systolic
      blood pressure (39+/-4 mm Hg, P<0.05). Concomitant treatment with losartan
      abolished the Ang II-induced pressure increase (P<0.05), whereas verapamil
      reduced it only partially (P<0.05). In the aortas of rats with Ang II-induced
      hypertension, tissue endothelin-1 content was increased threefold and
      contractions to endothelin-1 were impaired (P<0.05). Interestingly, these
      alterations were normalized by losartan (P<0.05) but not by verapamil. Hence,
      there was a strong, negative correlation between contractions to endothelin-1 and
      tissue endothelin-1 content (r=-0.733, P<0.0001). In contrast, both
      antihypertensive drugs normalized impaired endothelium-dependent relaxations to
      acetylcholine and reduced the sensitivity of vascular smooth muscle to sodium
      nitroprusside compared with Ang II-treated rats (P<0.05). Ang II-induced
      hypertension enhanced endothelium-dependent contractions to acetylcholine, and
      these were normalized by either drug. In conclusion, these findings suggest that
      long-term treatment with Ang II modulates endothelin-1 protein expression in the
      rat aorta. Although both antihypertensive agents lowered blood pressure and
      normalized endothelial function, only losartan prevented the increase in tissue
      endothelin-1 content, suggesting that angiotensin type 1 receptor antagonists but
      not calcium antagonists modulate tissue endothelin-1 in vivo.

PMID- 9622147
TI  - Dose-related efficacy of irbesartan for hypertension: an integrated analysis.
AB  - Results of eight multicenter, randomized, placebo-controlled, double-blind,
      parallel-group studies were pooled to assess the efficacy of the angiotensin II
      receptor blocker irbesartan over the dose range of 1 to 900 mg. A total of 2955
      adults with a seated diastolic blood pressure of 95 to 110 mm Hg were randomized
      to treatment with oral irbesartan once daily or placebo for 6 to 8 weeks. Office
      blood pressure was measured at trough (24+/-3 hours after the last dose) and peak
      (3+/-1 hours after the last dose) by mercury sphygmomanometry. Demographic
      characteristics (mean blood pressure; 151/101 mm Hg; mean age, 54 years; 63%
      male; and 82% white) were similar across all dose groups. After the groups were
      pooled, antihypertensive efficacy was assessed by therapeutic response (trough
      seated diastolic blood pressure <90 mm Hg or a reduction from baseline of > or =
      10 mm Hg) and by modeling of the maximum reductions in trough and peak seated
      diastolic and systolic blood pressure. Antihypertensive effects increased with
      increasing doses and reached a plateau at > or = 300 mg. Irbesartan 150 mg
      provided placebo-subtracted reductions in trough seated systolic and diastolic
      blood pressure of approximately 8 and approximately 5 mm Hg, respectively, with
      56% of patients displaying a favorable response. In conclusion, irbesartan
      provides clinically significant blood pressure lowering, with a clear
      relationship between (log) dose and antihypertensive effect.

PMID- 9622148
TI  - Reduction of cold-induced hypertension by antisense oligodeoxynucleotides to
      angiotensinogen mRNA and AT1-receptor mRNA in brain and blood.
AB  - Rats exposed chronically to mild cold (5 degrees C/41 degrees F) develop
      hypertension and cardiac hypertrophy. This provides a unique model of
      hypertension that is environmentally induced. The blood renin-angiotensin system
      (RAS) has been shown to play a role in both initiating and maintaining the high
      blood pressure (BP) in cold-induced hypertension. The mechanism also appears to
      involve both the tissue and brain RAS because there is increased mRNA for
      angiotensinogen (AGT) and angiotensin type 1 (AT1) receptors in brain and
      peripheral tissues, an increased spontaneous drinking response, and an increased
      dipsogenic response to acute administration of angiotensin II (Ang II) in cold
      treated rats. Antisense oligodeoxynucleotides (AS-ODN), targeted to the RAS, have
      been shown to reduce BP in spontaneously hypertensive rats. Therefore, we
      injected AS-ODN in rats with cold-induced hypertension to test whether antisense
      inhibition was effective in reducing this nongenetic nonsurgical hypertension.
      Sprague-Dawley rats were made hypertensive by cold exposure and injected
      intracerebroventricularly with AS-ODN to AGT mRNA (n=6) or AT1 receptor mRNA
      (n=6). Systolic BP was recorded by tail cuff 24 hours later for 2 or 7 days,
      respectively. Systolic BP decreased significantly in response to AGT-AS-ODN (40+/
      6 mm Hg, P<0.01) within 1 day after injection and to AT1 receptor-AS-ODN (P<0.05)
      for 3 days after injection. The maximum decrease was 41+/-10 mm Hg. Systolic BP
      then gradually increased to the preinjection level. The spontaneous drinking
      response to cold treatment also decreased significantly (P<0.05) after AGT-AS-ODN
      or AT1 receptor-AS-ODN intracerebroventricular injection. Intracardiac injection
      of AT1-AS-ODN (n=6) reduced systolic BP by 36+/-8 mm Hg (P<0.05) and decreased
      AT1 receptor as measured by autoradiography in aorta, adrenal glands, and kidneys
      24 hours after injection. These data show that AS-ODN reduces BP in cold-induced
      hypertension and that the hypertension involves both peripheral tissues and
      central RAS in addition to blood-borne RAS mechanisms.

PMID- 9622149
TI  - Blood pressure-independent cardiac hypertrophy induced by locally activated renin
      angiotensin system.
AB  - Cardiac hypertrophy is frequent in chronic hypertension. The renin-angiotensin
      system, via its effector angiotensin II (Ang II), regulates blood pressure and
      participates in sustaining hypertension. In addition, a growing body of evidence
      indicates that Ang II acts also as a growth factor. However, it is still a matter
      of debate whether the trophic effect of Ang II can trigger cardiac hypertrophy in
      the absence of elevated blood pressure. To address this question, transgenic mice
      overexpressing the rat angiotensinogen gene, specifically in the heart, were
      generated to increase the local activity of the renin-angiotensin system and
      therefore Ang II production. These mice develop myocardial hypertrophy without
      signs of fibrosis independently from the presence of hypertension, demonstrating
      that local Ang II production is important in mediating the hypertrophic response
      in vivo.

PMID- 9622150
TI  - Angiotensin II induces vascular smooth muscle cell replication independent of
      blood pressure.
AB  - The purpose of this investigation was to evaluate the role of blood pressure in
      the proliferative response of vascular smooth muscle cells to systemic infusion
      of angiotensin II (Ang II). Our laboratory has previously shown that infusion of
      Ang II induces smooth muscle cell proliferation in rat mesenteric vessels and
      carotid arteries. Ang II, a strong vasopressor, raised systolic blood pressure in
      rats from 120 to 200 mm Hg at a dose of 435 ng x kg(-1) x min(-1) after 1 week of
      treatment. The question arises as to whether this development of hypertension is
      a primary contributor to the replicative activities observed in the arterial wall
      of the mesenteric arteries or the carotid arteries or whether Ang II alone,
      without an increase in blood pressure, is sufficient to stimulate proliferation
      in these vessels. In the previous studies, we found that Ang II stimulated smooth
      muscle cell replication in the carotid artery and in type III and type I
      mesenteric microvessels. This study demonstrates that although administration of
      hydralazine normalizes the animals' blood pressures, it does not suppress the
      mitogenic effect of Ang II. Thus, it appears that Ang II has a direct effect on
      cell proliferation.

PMID- 9622151
TI  - Suppression of ANP gene transcription by liganded vitamin D receptor: involvement
      of specific receptor domains.
AB  - We showed previously that liganded vitamin D receptor (VDR) effects a suppression
      of human atrial natriuretic peptide (hANP) gene-promoter activity in cultured
      neonatal rat atrial myocytes. In the present study, we have attempted to identify
      the structural domains of the VDR that are involved in mediating this
      suppression. We examined the effects of a series of VDR mutants on a
      cotransfected hANP promoter-driven chloramphenicol acetyltransferase (CAT)
      reporter. Neither the native VDR nor any of the mutants tested displayed
      inhibitory activity in the absence of the 1,25-dihydroxyvitamin D3 (VD3) ligand.
      Delta134, a deletant harboring solely the DNA binding region of the VDR, and
      L254G, a mutant shown to be defective in retinoid X receptor (RXR) heterodimer
      formation in other systems, were as effective as the native VDR in reducing
      promoter activity. HBD, a deletant containing only the hormone-binding domain of
      the VDR, and K246G, a point mutant that is defective in the activation function
      of the receptor, did not attenuate reporter activity. A similar activity profile
      was displayed when a positively regulated promoter containing a direct-repeat
      vitamin D responsive element (DR3-CAT) was examined in these cells. Liganded VDR,
      the delta134 mutant, and liganded L254G effected increases in DR3-CAT activity of
      2.5-, 2-, and 4-fold, respectively. Two nonhypercalcemic analogues of VD3 (RO 23
      7553 and RO 25-6760) displayed the same inhibitory activity as VD3. These studies
      suggest that the inhibition of hANP promoter activity requires both the DNA
      binding and activation functions of the receptor but does not appear to require
      formation of a classic RXR alpha-VDR heterodimer.

PMID- 9622152
TI  - Eclamptic plasma stimulates norepinephrine release in cultured sympathetic nerve.
AB  - The purpose of the present study was to evaluate the effect of plasma from
      eclamptic and preeclamptic patients on cultured sympathetic nerve. Sympathetic
      neurons from 12- to 14-day-old chick embryos were cultured; the neurons were then
      stimulated with 50% plasma from eclamptic, preeclamptic, hypertensive,
      normotensive pregnant, hypertensive, and normotensive nonpregnant women (n=7).
      Similarly, neurons were individually incubated with mixtures of 50% corresponding
      plasma with 0.25% bupivacaine or bupivacaine only (n=7). Furthermore, the effects
      of 1%, 10%, and 50% plasma from eclamptic, preeclamptic, and normotensive
      pregnant patients (n=7) were also evaluated. Norepinephrine concentrations were
      measured by high-performance liquid chromatography. Electron microscopic studies
      of nerve cells were also performed. Stimulation with plasma from eclamptic and
      preeclamptic women significantly increased norepinephrine concentration
      (P<0.0001) compared with control. The release of norepinephrine was found to be
      concentration-dependent. Conversely, norepinephrine secretion was significantly
      hampered by bupivacaine treatment (P<0.0001). Electron microscopic studies in
      eclamptic and preeclamptic plasma-stimulated nerve cells showed that perikarya
      were in close contact with each other and with nerve cell processes. After
      treatment with bupivacaine, nerve cells were irregular in shape and the cell
      membranes were demyelinated. These results suggest that eclamptic and
      preeclamptic plasma has an excitotoxic effect on sympathetic nerve via axoplasmic
      membrane depolarization, thus increasing norepinephrine secretion that is blocked
      by bupivacaine. A preeclamptic condition may be improved by depression of
      sympathetic nerve stimulation.

PMID- 9622153
TI  - Resistance to endotoxin shock in spontaneously hypertensive rats.
AB  - Septic shock involves systemic vasodilation mediated by proinflammatory
      cytokines. In essential hypertension, vascular and immune dysfunctions are
      closely associated. The response of hypertensive animals compared with
      normotensive controls to endotoxin (lipopolysaccharide; LPS) challenge is not
      known. Age-matched (12 weeks) normotensive Wistar-Kyoto rats (WKY) and
      spontaneously hypertensive rats (SHR) were exposed to intravenous injection of 10
      mg/kg LPS. Survival rate at 24 hours was markedly higher in SHR than in WKY (12
      of 15 and 3 of 15, respectively; P<0.01). Survival of LPS-injected SHR was not
      related to their hypertension because hydralazine-treated SHR with normalized
      pressure had similar survival rates, and WKY made hypertensive by clipping of one
      renal artery showed fatality similar to that of normotensive WKY. Continuous
      arterial pressure and sequential plasma levels of interleukin-6 (IL-6) and tumor
      necrosis factor (TNF) were measured in LPS-treated SHR and WKY. Both the duration
      of the delayed hypotensive phase and the systemic release of IL-6 were much lower
      in SHR than WKY, whereas both acute hypotension and plasma TNF peak were
      equivalent. We further explored in vitro the inflammatory response and showed
      that LPS-activated whole blood from SHR produced less TNF and IL-6 than WKY LPS
      activated whole blood. Our results indicate that SHR have a greater ability to
      resist endotoxic shock than WKY. This is not related to their hypertension but is
      associated with an attenuated inflammatory response to LPS.

PMID- 9622154
TI  - Application of transcription factor "decoy" strategy as means of gene therapy and
      study of gene expression in cardiovascular disease.
AB  - Recent progress in molecular biology has provided new techniques for inhibiting
      target gene expression. In particular, the application of DNA technology, such as
      antisense strategy to regulate the transcription of disease-related genes in
      vivo, has important therapeutic potential. Recently, transfection of cis-element
      double-stranded oligodeoxynucleotides (ODNs), referred to as "decoy" ODNs, has
      been reported to be a powerful tool in a new class of anti-gene strategies for
      gene therapy and in the study of transcriptional regulation. Transfection of
      double-stranded ODNs corresponding to the cis sequence will result in the
      attenuation of authentic cis-trans interaction, leading to the removal of trans
      factors from the endogenous cis elements with subsequent modulation of gene
      expression. This "decoy" strategy is not only a novel strategy for gene therapy
      as an anti-gene strategy but also a powerful tool for the study of endogenous
      gene regulation in vivo as well as in vitro. In this article, we reviewed (1) the
      mechanisms and (2) the potential applications of decoy strategy.

PMID- 9622155
TI  - Comparison of unitary displacements and forces between 2 cardiac myosin isoforms
      by the optical trap technique: molecular basis for cardiac adaptation.
AB  - To provide information on the mechanism of cardiac adaptation at the molecular
      level, we compared the unitary displacements and forces between the 2 rat cardiac
      myosin isoforms, V1 and V3. A fluorescently labeled actin filament, with a
      polystyrene bead attached, was caught by an optical trap and brought close to a
      glass surface sparsely coated with either of the 2 isoforms, so that the actin
      myosin interaction took place in the presence of a low concentration of ATP (0.5
      micromol/L). Discrete displacement events were recorded with a low trap stiffness
      (0.03 to 0.06 pN/nm). Frequency distribution of the amplitude of the
      displacements consisted of 2 gaussian curves with peaks at 9 to 10 and 18 to 20
      nm for both V1 and V3, suggesting that 9 to 10 nm is the unitary displacement for
      both isoforms. The duration of the displacement events was longer for V3 than for
      V1. On the other hand, discrete force transients were recorded with a high trap
      stiffness (2.1 pN/nm), and their amplitude showed a broad distribution with mean
      values between 1 and 2 pN for V1 and V3. The durations of the force transients
      were also longer for V3 than for V1. These results indicate that both the unitary
      displacements and forces are similar in amplitude but different in duration
      between the 2 cardiac myosin isoforms, being consistent with the reports that the
      tension cost is higher in muscles consisting mainly of V1 than those consisting
      mainly of V3.

PMID- 9622156
TI  - Recombinant murine interleukin-12 facilitates induction of cardiac myosin
      specific type 1 helper T cells in rats.
AB  - Autoimmunity after viral myocarditis is considered to be one of the causes of
      dilated cardiomyopathy. Cytokines are assumed to play an important role in the
      pathogenesis. We recently reported that interleukin (IL)-2 and interferon (IFN)
      gamma mRNA are expressed in the myocardium of rats with experimental autoimmune
      myocarditis (EAM). However, the role of cytokines in autoimmune myocardial injury
      in detail is still not clear. Reverse transcription-polymerase chain reaction
      identified IL-12 (p40) mRNA in antigen-presenting cells in the initial phase of
      EAM. Cardiac myosin-specific T lymphocytes (MSTLs) were cultured with cardiac
      myosin peptide (CMP) in the presence of IL-2 and/or IL-12 and were transferred to
      other naive rats. The results showed that EAM could be effectively induced by
      transfer of MSTLs cultured with IL-12, whereas transfer of MSTLs cultured with IL
      2 was less effective. However, IL-2 acts synergistically with IL-12, and MSTLs
      cultured with both cytokines most efficiently induce EAM. In vitro experiments
      showed that MSTLs cultured with both IL-12 and IL-2 produced a much greater
      amount of IFN-gamma than did MSTLs cultured with either IL-12 or IL-2 alone. The
      amount of IFN-gamma production was correlated with pathogenicity of MSTLs.
      Transfer experiments after sorting further demonstrated that the transfer was
      affected by CD4+ helper T (Th) cells but not by CD8+ cytotoxic T lymphocytes. IL
      12 and IL-2 synergistically enhance the pathogenicity of MSTLs. Furthermore, a
      type 1 Th (Th1) cytokine, IFN-gamma, which is a potent regulatory cytokine of
      autoimmunity, is produced by MSTLs. IL-12 and IL-2 potentiate the expansion of
      cardiac myosin-specific Th1 cells and play an important role in the development
      of autoimmune myocardial injury.

PMID- 9622157
TI  - Epicardium-derived cells contribute a novel population to the myocardial wall and
      the atrioventricular cushions.
AB  - The epicardium and dorsal mesocardium are known to be the source of structures
      that form the wall of the coronary vessels. Because mouse knockout studies have
      shown that proper epicardial formation is also essential for myocardial
      development, we have studied in detail the migration and differentiation of
      epicardium-derived cells (EPDCs) within the developing heart. We constructed
      chicken-quail chimeras by grafting the quail epicardial organ, including a piece
      of primordial liver, at essentially stages 16 and 17. The embryos were studied at
      stages 25 to 43. To detect quail-derived EPDCs, an anti-quail nucleus antibody
      was used in combination with several differentiation markers, eg, for muscle
      actin, for vascular smooth muscle cells, for procollagen-I, for quail
      endothelium, and for Purkinje fibers. At stages 25 to 31, EPDCs are encountered
      in the myocardial wall and the subendocardial region. The latter deposition is
      spatially facilitated as the endocardium protrudes through transient
      discontinuities in the myocardium to contact the subepicardial layer. Later on,
      at stages 32 to 43, EPDCs invaded, by way of the atrioventricular sulcus, the
      atrioventricular cushion tissue. The localization is apparent at the interface
      with the myocardium, as well as subendocardially, but never within the
      endocardial lining. The origin of endothelium, smooth muscle cells, and
      fibroblasts of the coronary vessel wall from the epicardial graft were confirmed
      in accordance with already published data. The functional role of the novel EPDCs
      in the subendocardium, myocardium, and atrioventricular cushions remains to be
      investigated. A close positional relationship is found with the differentiating
      Purkinje fibers. Furthermore, a regulatory role is postulated in the process of
      endocardial-mesenchymal transformation. The ultimate fate of EPDCs seems to be a
      cardiac fibroblast cell line involved in the formation of the fibrous heart
      skeleton.

PMID- 9622158
TI  - Hydrogen peroxide activates mitogen-activated protein kinases and Na+-H+ exchange
      in neonatal rat cardiac myocytes.
AB  - Reperfusion of cardiac tissue after an ischemic episode is associated with
      metabolic and contractile dysfunction, including reduced tension development and
      activation of the Na+-H+ exchanger (NHE). Oxygen-derived free radicals are key
      mediators of reperfusion abnormalities, although the cellular mechanisms involved
      have not been fully defined. In the present study, the effects of free radicals
      on mitogen-activated protein (MAP) kinase function were investigated using
      cultured neonatal rat ventricular myocytes. Acute exposure of spontaneously
      beating myocytes to 50 micromol/L hydrogen peroxide (H2O2) caused a sustained
      decrease in contraction amplitude (80% of control). MAP kinase activity was
      measured by in-gel kinase assays and Western blot analysis. Acute exposure to
      H2O2 (100 micromol/L, 5 minutes) resulted in sustained MAP kinase activation that
      persisted for 60 minutes. Catalase, but not superoxide dismutase, completely
      inhibited MAP kinase activation by H2O2. Pretreatment with chelerythrine (10
      micromol/L, 45 minutes), a protein kinase C inhibitor, or genistein (75
      micromol/L, 45 minutes) or herbimycin A (3 micromol/L, 45 minutes), tyrosine
      kinase inhibitors, caused significant inhibition of H2O2-stimulated MAP kinase
      activity (51%, 78%, and 45%, respectively, at 20 minutes). Brief exposure to H2O2
      also stimulated NHE activity. This effect was completely abolished by
      pretreatment with the MAP kinase kinase inhibitor PD 98059 (30 micromol/L, 60
      minutes). These results suggest that low doses of H2O2 induce MAP kinase
      dependent pathways that regulate NHE activity during reperfusion injury.

PMID- 9622159
TI  - Purkinje-muscle reentry as a mechanism of polymorphic ventricular arrhythmias in
      a 3-dimensional model of the ventricles.
AB  - Multiple electrode mapping of the ventricles during complex tachyarrhythmias has
      revealed focal subendocardial activation whose mechanism remains unexplained. We
      hypothesized that reentry involving the Purkinje-muscle junctions (PMJs) may be a
      mechanism for such focal excitations. We have constructed an anatomically
      appropriate computerized 3-dimensional model of the mammalian ventricles that
      includes the Purkinje conduction system and 214 PMJs distributed throughout the
      endocardium. Isochronal maps during normal excitation, as well as during right or
      left bundle branch block, resembled experimental measurements and compared well
      with isochronal maps of propagation in the human heart. Activity observed at both
      sides of a PMJ in the model showed that propagation from Purkinje fibers to
      muscle was slower than in the opposite direction. Under these realistic and
      normal conditions, the evolution of reentrant activity involving muscle and the
      Purkinje network was simulated. The reentry pattern was independent of the
      initiation site. It evolved with drifting epicardial breakthroughs and
      transformed on the endocardium from focal activity to figure-of-8 reentry. In
      addition, the ECG amplitude undulated during the evolution, and decrease in the
      cycle period, apparent wavelength, and propagation velocity were observed.
      Finally, the reentry was terminated if the Purkinje system was disconnected from
      the muscle before it reached a relative steady state. The simulation results
      suggest the following: (1) Epicardial breakthroughs and endocardial focal
      activity may originate at the PMJs. (2) The ECG amplitude may decrease as the
      reentry stabilizes and the excitation wavelength decreases. (3) The Purkinje
      system may have a double role in the evolution of reentry: first, it is essential
      to the reentry at the initial stage; second, it may lead to the establishment of
      intramyocardial reentry, at which time the Purkinje system becomes irrelevant.

PMID- 9622160
TI  - Alpha1-adrenergic stimulation of sarcolemmal Na+-H+ exchanger activity in rat
      ventricular myocytes: evidence for selective mediation by the alpha1A
      adrenoceptor subtype.
AB  - Alpha1-adrenoceptor (alpha1-AR) stimulation increases sarcolemmal Na+-H+
      exchanger (NHE) activity. The present study was designed to determine the role(s)
      of alpha1-AR subtype(s) in mediating this response. As an index of NHE activity,
      acid efflux rates (JHs) were determined in single rat ventricular myocytes loaded
      with the pH-sensitive fluoroprobe carboxy-seminaphthorhodafluor-1 after 2
      consecutive intracellular acid pulses in bicarbonate-free medium. JH at pHi 6.90
      did not change significantly during the second pulse relative to the first in
      control cells but increased in a dose-dependent manner when the second pulse
      occurred in the presence of phenylephrine (nonselective alpha1-AR agonist) or
      A61603 (alpha1A-AR-selective agonist), with EC50 values of 1.24 micromol/L and
      3.6 nmol/L, respectively (both agonists given together with 1 micromol/L
      atenolol). Stimulation of NHE activity by 10 micromol/L phenylephrine was
      inhibited in a dose-dependent manner by the competitive antagonists prazosin,
      WB4101, and 5-methylurapidil, with IC50 values of 12, 32, and 149 nmol/L,
      respectively. Analyses of the relative EC50 and IC50 values obtained (and Ki
      values estimated from the antagonist IC50s) in relation to the relative potencies
      of these agents at native rat alpha1-AR subtypes and their relative affinities
      for recombinant rat alpha1-ARs suggest that alpha1-adrenergic stimulation of
      sarcolemmal NHE activity is likely to be mediated selectively by the alpha1A-AR.

PMID- 9622161
TI  - Plasminogen activator expression in rat arterial smooth muscle cells depends on
      their phenotype and is modulated by cytokines.
AB  - Cultured rat aortic smooth muscle cells (SMCs) exhibit at least 2 phenotypic
      variants: (1) a spindle-shaped phenotype, obtained from normal adult media, and
      (2) an epithelioid phenotype, obtained from intimal thickening 15 days after
      endothelial injury. Both phenotypes can be cloned from each location, with normal
      media yielding a majority of spindle-shaped clones and intimal thickening
      yielding a majority of epithelioid clones. These findings suggest that intimal
      thickening develops essentially from a subpopulation of medial SMCs exhibiting
      epithelioid features in vitro. Using zymographic and Northern blot analyses, we
      have studied plasminogen activator (PA) expression by these SMCs. Our results
      show that epithelioid SMCs, cultured as whole SMC populations or as clones,
      display higher PA activity than do spindle-shaped SMCs, irrespective of their
      origin. This is mainly due to differences in the expression of tissue PA and, to
      a lesser extent, urokinase PA and is accompanied by a decrease in PA inhibitor 1.
      Tissue PA activity is increased by basic fibroblast growth factor and platelet
      derived growth factor-BB, particularly in epithelioid SMCs. Taken together, these
      results indicate that SMCs are heterogeneous with respect to their proteolytic
      profile, at least as far as the PA system is concerned. Proteolytic activity of
      the different SMC populations is modulated by cytokines that play a role in
      intimal thickening. Our results are in agreement with the suggestion that
      epithelioid SMCs are mainly responsible for intimal thickening.

PMID- 9622162
TI  - Oscillatory and steady laminar shear stress differentially affect human
      endothelial redox state: role of a superoxide-producing NADH oxidase.
AB  - Atherosclerotic lesions are found opposite vascular flow dividers at sites of low
      shear stress and oscillatory flow. Since endothelial proinflammatory genes
      prominent in lesions are regulated by oxidation-sensitive transcriptional control
      mechanisms, we examined the redox state of cultured human umbilical vein
      endothelial cells after either oscillatory or steady laminar fluid shear stress.
      Endothelial oxidative stress was assessed by measuring activity of the superoxide
      (O2.- )-producing NADH oxidase (a major source of reactive oxygen species in
      vascular cells), intracellular O2.- levels, induction of the redox-sensitive gene
      heme oxygenase-1 (HO-1), and abundance of Cu/Zn superoxide dismutase (Cu/Zn SOD),
      an antioxidant defense enzyme whose level of expression adapts to changes in
      oxidative stress. When cells were exposed to oscillatory shear (+/-5 dyne/cm2, 1
      Hz) for 1, 5, and 24 hours, NADH oxidase activity and the amount of HO-1
      progressively increased up to 174+/-16% (P<0.05) and 505+/-111% (P<0.05) versus
      static conditions, respectively, whereas levels of Cu/Zn SOD remained unchanged.
      This upregulation of HO-1 was completely blocked by the antioxidant N
      acetylcysteine (NAC, 20 mmol/L). In contrast, steady laminar shear (5 dyne/cm2)
      induced NADH oxidase activity and NAC-sensitive HO-1 mRNA expression only at 1
      and 5 hours, a transient response that returned toward baseline at 24 hours.
      Levels of Cu/Zn SOD mRNA and protein were increased after 24 hours of steady
      laminar shear. Furthermore, intracellular O2.-, as measured by dihydroethidium
      fluorescence, was higher in cells exposed to oscillatory than to laminar shear.
      These data are consistent with the hypothesis that continuous oscillatory shear
      causes a sustained activation of pro-oxidant processes resulting in redox
      sensitive gene expression in human endothelial cells. Steady laminar shear stress
      initially activates these processes but appears to induce compensatory
      antioxidant defenses. We speculate that differences in endothelial redox state,
      orchestrated by different regimens of shear stress, may contribute to the focal
      nature of atherosclerosis.

PMID- 9622163
TI  - Flow rate-modulated dissolution of fibrin with clot-embedded and circulating
      proteases.
AB  - The efficiency of plasmin, miniplasmin, and neutrophil leukocyte elastase in
      fibrin digestion is well characterized in static systems. Since in vivo the
      components of the fibrinolytic system are permanently exposed to flow, we have
      developed two in vitro models and studied the effect of shear forces on fibrin
      dissolution with these proteases. Cylindrical nonocclusive fibrin clots are
      perfused at various flow rates through their preformed axial channel, and
      dissolution of fibrin is followed by measuring the absorbance of degradation
      products released into the circulating fluid phase. In one experimental setting,
      fibrin surface is degraded with enzymes applied in the recirculating fluid phase;
      in another setting, clots containing gel-embedded proteases are perfused with
      enzyme-free buffer. As shear rate at fibrin surface is changed from 25 to 500 s(
      1), the rate of product release by recirculated enzymes increases 2.8-, 2.9-, and
      4-fold for plasmin, miniplasmin, and porcine pancreatic elastase, respectively.
      Buffer-perfused fibrin containing gel-embedded plasmin or miniplasmin is
      disintegrated by shear forces at a relatively early stage of dissolution, and
      this disassembly is related to the formation of fragment Y (150 kDa) and fragment
      D (100 kDa) fibrin degradation products. Fibrin clots degraded by incorporated
      polymorphonuclear leukocyte elastase, which yields different degradation
      products, do not disassemble abruptly, even at the highest shear rate (500 s(
      1)). Our results suggest that fibrin surface degradation is accelerated with
      increasing shear rate and that plasmin or miniplasmin embedded in the clot
      promotes the release of particular clot remnants into the circulating phase,
      whereas polymorphonuclear leukocyte elastase does not.

PMID- 9622164
TI  - How actin-myosin interactions differ with different isoforms of myosin.

PMID- 9622165
TI  - Epidemiology of eclampsia in Colombia.
AB  - OBJECTIVE: To measure the incidence of eclampsia, its maternal and perinatal
      outcomes and patterns of presentation of this disease in our environment. METHOD:
      Retrospective descriptive study of 164 cases of eclampsia managed at the Hospital
      Universitario del Valle, Cali, Colombia from September 1993 to August 1995.
      Information was collected from reviews of hospital case-notes. RESULTS: The
      incidence of eclampsia was 8.1/1000 deliveries. Maternal mortality was 6.1%.
      Fifty-seven percent of seizures occurred antepartum, 22% during labor, and 21%
      after delivery. Sixty-nine cases (42%) presented preterm. Ninety-eight women
      (60%) were nulliparous. Approximately one quarter of the women did not have
      hypertension or significant proteinuria at the time of seizures. Twenty percent
      of all women had at least one major complication. Perinatal mortality was 12.8%.
      Antepartum and postpartum cases were more severe than intrapartum cases.
      CONCLUSION: Eclampsia occurs in one in 124 deliveries in Cali, Colombia and is
      associated with high maternal and perinatal morbidity and mortality.

PMID- 9622166
TI  - A simplified fetal biophysical profile.
AB  - OBJECTIVE: To modify the classic fetal biophysical profile (FBP) with the aim of
      obtaining rapid and accurate information about actual fetal condition in non
      compromised fetuses with a subsequent favorable outcome and to be suitable for a
      number of outclinic patients. METHODS: Four-hundred and ninety-four fetuses from
      singleton pregnancies in two randomized groups were monitored by the modified FBP
      (mFBP) and 168 of them after the external vibratory acoustic stimulation
      (VAS/mFBP). The mFBP was characterized by two main characteristics: non-stress
      test was excluded and the testing was finished at the moment when all of the
      three fetal biophysical activities became normal. The external VAS was applied
      only in cases with no evidence of fetal activity at the start of the FBP.
      RESULTS: Of the examined fetuses, 326 fetuses in the control group were monitored
      by the mFBP and there were 316 (96.9%) favorable outcomes and 10 (3.1%) adverse
      perinatal outcomes. The sensitivity, specificity and positive and negative
      predictive values of the mFBP score in predicting adverse perinatal outcome were
      60, 99, 66.7 and 98.7%, respectively. In the study group of 168 fetuses there
      were 165 (98.2%) favorable outcomes and three (1.8%) adverse perinatal outcomes.
      The sensitivity, specificity and positive and negative predictive values of the
      VAS/mFBP were 66.7, 100, 100 and 99.4%, respectively. The efficiency of the
      VAS/mFBP in predicting perinatal mortality alone was even higher. After the
      external VAS and the first 5 min of the modified testing approximately two-fifths
      (41.8%) of healthy fetuses with a subsequent good outcome exhibited normal in all
      of the three biophysical activities and approximately two-thirds (65.5%) of them
      after 10 min. In the VAS/mFBP group of healthy fetuses, during the same time
      periods, normal breathing movements were observed in 72% and 87% of fetuses,
      respectively. CONCLUSIONS: According to our results the mFBP and particularly the
      VAS/mFBP antenatal protocol as a new and rational variant of the FBP could
      improve fetal assessment allowing in cases of non-compromised fetuses rapid and
      accurate information about actual fetal well-being. Because of its high accuracy
      and a reduced testing time the antepartal method with observation of fetal
      breathing movements after VAS is becoming acceptable as a screening of fetal well
      being evaluation in outclinic conditions.

PMID- 9622167
TI  - Thrombocytopenia, hypertension and seizures in eclampsia.
AB  - OBJECTIVE: Mortality by eclampsia most likely relies on factors that are
      associated with seizures, but not directly related to them. The objective of the
      current study is to analyze these probable factors. METHOD: This study evaluates
      patients with eclampsia only. Age, parity, weeks of gestation, blood pressure,
      platelet counts and cause of death were analysed. The groups of survivors and
      fatalities were compared using relative risk (RR) with 95% confidence intervals
      (CI), chi2 and Student's t-test. RESULTS: A total of 446 cases of eclampsia were
      studied, of which there were 371 survivors and 75 deaths. The incidence was
      14.2/10000 births with mortality of 14.4%. Mortality was more frequent in
      patients over 25 years of age (P < 0.005). The diastolic blood pressure showed
      significant difference between the survivor and fatality group (P < 0.05). Before
      convulsion, thrombocytopenia was present in 148 patients (33.2%) of which 95
      survived and 53 died (RR = 2.76; 95% CI 2.20-3.46; P < 0.0000001). CONCLUSIONS:
      Mortality by eclampsia is directly related to age, diastolic blood pressure > or
      = 110 mmHg, seizure and thrombocytopenia. Our findings suggest poor maternal
      prognosis if seizures occur associated with thrombocytopenia.

PMID- 9622168
TI  - A morphometric study of maternal smoking on apoptosis in the syncytiotrophoblast.
AB  - OBJECTIVES: To study syncytiotrophoblast apoptosis in the placenta of smoking and
      non-smoking pregnant women. METHODS: Twelve neonates, pregnancies and placentas
      were available for study. Eight mothers smoked during pregnancy and the remaining
      four were non-smokers used as control subjects. The main outcome measure was the
      apoptotic syncytiotrophoblast index for each group. Apoptosis was detected by
      immunohistochemistry using the TUNEL method and quantitatively measured using a
      Merz grid. The apoptotic syncytiotrophoblast index was calculated as the ratio of
      mean apoptotic labeling to percent terminal villus area using high-power field
      microscopy. RESULTS: Significant differences in apoptotic syncytiotrophoblast
      index were observed between the control group (15.06+/-3.72) and the smoker group
      (1.66+/-1.74) (P < 0.0001, Mann-Whitney test), but no differences were detected
      in clinical or morphometric data between groups. CONCLUSIONS: The human placental
      syncytiotrophoblast undergoes apoptosis and this process is associated with
      inhibition of apoptosis by the smoking habit. The same way as the presence of
      trophoblast apoptosis is associated with modifications of the maternal-fetal
      exchange, the inhibitory effect of the smoking habit on syncytiotrophoblast could
      be responsible for the poor prognosis of pregnancy in the presence of maternal
      smoking.

PMID- 9622169
TI  - Detection of Chlamydia trachomatis intrauterine infection using polymerase chain
      reaction on chorionic villi.
AB  - OBJECTIVE: To detect Chlamydia trachomatis intrauterine infection in the early
      pregnancy by using chorionic villi. METHOD: The C. trachomatis infection in
      pregnant women was investigated by cervical specimens and Clearview kits. DNA of
      chorionic villi was extracted and the gene of a major outer membrane protein of
      C. trachomatis was amplified by polymerase chain reaction (PCR). RESULTS: 120
      cervical specimens of the pregnant women were analyzed and 10 cervical specimens
      were positive for C. trachomatis infection. In this study, the prevalence of C.
      trachomatis infection was approx. 8.3%. Fifty-nine specimens of chorionic villi
      and three positive specimens of C. trachomatis infection were analyzed by PCR.
      The incidence of C. trachomatis intrauterine infection in the early pregnancy was
      5.1%. CONCLUSION: The vertical transmission of C. trachomatis infection in the
      early pregnancy may be a pathway of intrauterine infection. Chorionic villus
      sampling in early pregnancy and the PCR method could be developed as a technique
      for prenatal diagnosis of C. trachomatis intrauterine infection.

PMID- 9622170
TI  - Prenatal diagnosis of osteogenesis imperfecta type II.
AB  - OBJECTIVE: To characterize the prenatal sonographic features of osteogenesis
      imperfecta (OI) type II. DESIGN: Descriptive (case series). SETTING: Department
      of Obstetrics and Gynecology, Faculty of Medicine, Maharaj Nakorn Chiang Mai
      Hospital, Chiang Mai University. SUBJECTS: Six fetuses with prenatal diagnosis of
      OI were evaluated. RESULTS: Six fetuses were prenatally diagnosed as OI type II
      in five mothers without familial history of the disease. One mother had two
      consecutive pregnancies complicated with this condition. The first five cases
      were classified as OI type IIA, while the last one was OI type IIB. All of
      subtype A exhibited typical triad of bone shortening, diffuse hypomineralization
      and multiple fractures of long bones including beaded ribs whereas the subtype B
      showed shortening of only femurs, normal bone echodensity and isolated fractures
      of long bones. The postnatal radiography and autopsy confirmed the prenatal
      diagnosis in all cases. Other findings may occasionally be found, including
      polyhydramnios, oligohydramnios, hydrop fetalis and small for gestational age.
      CONCLUSION: The triad of bone shortening, decreased bone density and numerous
      fractures including beaded ribs permits a confident diagnosis of OI type IIA.
      Furthermore, sonographic features may differentiate the subtype of OI type II,
      depending on degree of bone shortening and echodensity.

PMID- 9622171
TI  - Antiphospholipid antibodies and lipoprotein (a) in women with recurrent fetal
      loss.
AB  - OBJECTIVE: To estimate the occurrence of lupus anticoagulant, both isotypes of
      anticardiolipins, IgG and IgM, and lipoprotein (a) in women with recurrent fetal
      loss. METHOD: 43 women with two or more fetal losses were included in this open,
      prospective study. They were divided into a group of 32 nullipara who have had
      only miscarriages and a group of 11 women who besides the fetal losses were able
      to give birth to at least one live newborn. Two control groups were also added:
      35 women who were never pregnant and 15 parous who did not have any miscarriage.
      The presence of lupus anticoagulant was assessed by the Staclot LA clotting test.
      IgG and IgM isotypes of anticardiolipins and lipoprotein (a) were determined
      using the immunoenzymatic methods. RESULTS: Lupus anticoagulant was discovered in
      only one of 23 examined patients. Abnormally high values of IgG isotype of
      anticardiolipins were found in two subjects of each control group and in two
      nullipara with miscarriages only. The increased level of IgM isotype was noted in
      approx. 50% of patients with recurrent fetal loss, but at least one successful
      delivery and in control subjects who were never pregnant. In contrast, the
      frequency of the increased level of this antibody was diminished by half in the
      remaining two groups: women who delivered a live child (children) without any
      miscarriage and women who had only miscarriages. Elevated levels of lipoprotein
      (a) were found in approx. 30% of non-pregnant control subjects and in the
      patients of both groups; the abnormally high concentration of this lipoprotein
      was encountered in only 13% of women who gave birth to live newborn(s) and did
      not have any miscarriage. CONCLUSION: Of all four determined variables, only
      abnormally high values of lipoprotein (a) may have some prognostic significance
      in women predisposed to the recurrent fetal loss.

PMID- 9622172
TI  - Human papillomavirus (HPV) DNA assay as an adjunct to liquid-based Pap test in
      the diagnostic triage of women with an abnormal Pap smear.
AB  - OBJECTIVE: The diagnostic performance and clinical value of the combined use of
      liquid-based Pap test and human papillomavirus testing were determined in 336
      patients with a previous abnormal smear. METHOD: Subsequent histologic evaluation
      was used as definitive diagnosis. RESULT: The combined use of liquid-based Pap
      test and HPV DNA testing showed higher rates in sensitivity (99.0%), specificity
      (59.3%), positive predictive value (89.9%) and negative predictive value (94.5%)
      than either cytology alone (sensitivity 98.8%, specificity 45.7%, positive
      predictive value 84.7%, negative predictive value 92.6%) or HPV DNA testing alone
      (sensitivity 84.9%, specificity 67.4%, positive predictive value 88.8%, negative
      predictive value 59.5%). CONCLUSION: The study demonstrated that the diagnostic
      accuracy for cervical cancer and its precursors was improved by using the liquid
      based Pap test as a primary diagnostic procedure and HPV assay as an adjunctive
      test. This information may assist the clinicians in triaging patients with
      equivocal cytologic cervical atypias.

PMID- 9622173
TI  - Pelvic examination, transvaginal ultrasound and transvaginal color Doppler
      sonography as predictors of ovarian cancer.
AB  - OBJECTIVE: To assess and compare the efficacy of pelvic examination, transvaginal
      ultrasound and transvaginal color Doppler imaging in differentiating benign and
      malignant ovarian tumors. METHODS: 34 patients with ovarian tumors scheduled for
      laparotomy underwent pelvic examination and a diagnosis of benign or malignant
      tumor was made. Transvaginal ultrasound was carried out to study the ovarian
      morphology followed by color Doppler imaging. A score of > or = 9 on Sassone
      scoring system or a pulsatility index < 1 was taken as suspicious for malignancy.
      RESULTS: Of all the three indicators (pelvic examination, transvaginal sonography
      and Doppler) transvaginal sonography had the highest sensitivity (100%) and
      Doppler had maximum specificity (96.29%) for predicting malignancy. However,
      statistical analysis did not show any difference in the predicting ability of
      these three modalities. CONCLUSION: Pelvic examination, transvaginal sonography
      and Doppler all had similar ability to predict malignancy in an adnexal mass.

PMID- 9622174
TI  - Pregnancy outcomes in El Salvador during the post-war period.

PMID- 9622175
TI  - Pre-operative suspicion of liver rupture during pregnancy.

PMID- 9622176
TI  - HIV, maternal anemia and perinatal intervention using zidovudine. DITRAME Study
      Group (ANRS 049 Clinical Trial).

PMID- 9622177
TI  - Single umbilical artery: correlation of the prognosis and side of the missing
      artery.

PMID- 9622178
TI  - cis-platinum-based chemotherapy in management of malignant ovarian germ cell
      tumors.

PMID- 9622179
TI  - C-erbB-2 expression in human proliferative and hyperplastic endometrium.

PMID- 9622180
TI  - Radical hysterectomy for cervical cancer in a unicornuate uterus.

PMID- 9622181
TI  - ACOG educational bulletin. Postpartum hemorrhage. Number 243, January 1998
      (replaces No. 143, July 1990). American College of Obstetricians and
      Gynecologists.

PMID- 9622182
TI  - ACOG committee opinion. Obstetrician-gynecologists' ethical responsibilities,
      concerns, and risks pertaining to adoption. Number 194, November 1997. Committee
      on Ethics. American College of Obstetricians and Gynecologists.

PMID- 9622183
TI  - Quality evaluation and improvement in practice antepartum external cephalic
      version. Number 30, January 1998. Committee on Quality Assessment. American
      College of Obstetricians and Gynecologists.

PMID- 9622184
TI  - Sustained visual-spatial attention produces costs and benefits in response time
      and evoked neural activity.
AB  - This study investigated the simple reaction time (RT) and event-related potential
      (ERP) correlates of biasing attention towards a location in the visual field. RTs
      and ERPs were recorded to stimuli flashed randomly and with equal probability to
      the left and right visual hemifields in the three blocked, covert attention
      conditions: (i) attention divided equally to left and right hemifield locations;
      (ii) attention biased towards the left location; or (iii) attention biased
      towards the right location. Attention was biased towards left or right by
      instructions to the subjects, and responses were required to all stimuli.
      Relative to the divided attention condition, RTs were significantly faster for
      targets occurring where more attention was allocated (benefits), and slower to
      targets where less attention was allocated (costs). The early P1 (100-140 msec)
      component over the lateral occipital scalp regions showed attentional benefits.
      There were no amplitude modulations of the occipital N1 (125-180 msec) component
      with attention. Between 200 and 500 msec latency, a late positive deflection
      (LPD) showed both attentional costs and benefits. The behavioral findings show
      that when sufficiently induced to bias attention, human observers demonstrate RT
      benefits as well as costs. The corresponding P1 benefits suggest that the RT
      benefits of spatial attention may arise as the result of modulations of visual
      information processing in the extrastriate visual cortex.

PMID- 9622185
TI  - Pitch perception: a difference between right- and left-handed listeners.
AB  - Various results indicate that the perception of a complex tone's "virtual" pitch
      is generally lateralized in the right cerebral hemisphere. The primary aim of
      this work was to test the hypothesis that this is not the case for the "spectral"
      pitch percepts induced by complex tones. Forty right-handed and 18 left-handed
      listeners were monaurally presented with pairs of successive tones made up of n
      consecutive equal-amplitude harmonics of a missing fundamental (F0). n varied
      from two to four across subjects. In "test" conditions, the paired tones differed
      in F0 but the spectral components of the tone with the lower F0 were higher in
      frequency than the corresponding components of the other tone (except for one
      component, which was identical). The subjects had to say if, from one tone to the
      other, pitch rose or fell. From such judgements, one could infer that the pitch
      dominantly perceived in each tone was a virtual pitch (corresponding to F0) or a
      spectral pitch (i.e., the pitch of a single spectral component, or a perceptual
      quality corresponding to the centroid of the power spectrum). For n = 2, the
      results indicated that virtual pitch was less salient than spectral pitch; the
      opposite occurred for n = 3 and n = 4. The ear (left or right) to which the
      stimuli were presented had some influence on the judgements, in the expected
      direction. However, this influence was not a robust one. Unexpectedly, a reliable
      effect of the listeners' handedness was observed: for each value of n, the
      judgements indicating virtual pitch perception were less frequent in the left
      handers than in the right-handers. Discrimination performances measured in
      "control" conditions showed that the handedness factor was not confounded with a
      factor of frequency discrimination ability.

PMID- 9622186
TI  - Ear advantage in dichotic listening after correction for early congenital hearing
      loss.
AB  - Twelve patients who had undergone surgical correction for either unilateral or
      bilateral congenital hearing loss were given a postoperative dichotic listening
      test for consonant vowel-consonant (CVC) words. Four normal hearing control
      subjects were also tested. Patients were first given a test of subjective
      loudness, and the level of presentation of stimuli in the atretic ear was
      adjusted accordingly. In the dichotic condition all controls exhibited a right
      ear advantage, and all unilateral atresia patients showed an ear advantage
      favouring the non-atretic ear. Patients with bilateral atresia essentially
      exhibited no ear advantage. Patients had the same error rate as controls in the
      dichotic condition, which suggests that ear advantage was not due to increased
      errors in the atretic ear. For patients there was a significant relationship
      between ear advantage and both preoperative interaural asymmetry in hearing loss
      and age at operation. Results suggest that a sensitive and critical period for
      development of the ear is complete by 5 years of age. Results also suggest some
      limited ability to adjust to permanent change in stimulation levels until, but
      not after, puberty.

PMID- 9622187
TI  - Brain potentials and syntactic violations revisited: no evidence for specificity
      of the syntactic positive shift.
AB  - One of the current issues in the investigation of language by means of event
      related brain potentials (ERPs) is whether there is an ERP effect that can be
      specifically related to the processing of syntactic information. It has been
      claimed that a late positivity (P600 or SPS-syntactic positive shift) occurring
      to syntactic violations or ambiguities qualifies as such an effect. In the
      present investigation we compared ERPs elicited by morphosyntactic (case
      inflection errors), semantic, and orthographic (misspelled words) violations in a
      group of young German subjects. All three types of violations gave rise to late
      positivities having the characteristics of the previously described P600/SPS. In
      an earlier time window, however, semantic violations were associated with a
      centroparietally distributed N400 component, whereas syntactic violations gave
      rise to a negativity of smaller amplitude that had a frontocentral distribution.
      In light of the present experiment, the view that the P600/SPS as a whole
      reflects specific syntactic processes appears to be untenable and an alternative
      interpretation is proposed. The different distributions of the late positive
      shifts merit further investigation.

PMID- 9622188
TI  - Perception and action in hemispatial neglect.
AB  - Hemispatial neglect is a neurological disorder which entails a spatial bias that
      penalizes events occurring in the hemispace contralateral to a brain lesion.
      Mechanisms operating upon various stages ranging from perception to action have
      been invoked to explain neglect. The present study explores the contribution of a
      defective programming of arm movements towards the neglected hemispace to neglect
      behaviour. Two reaction time tasks -- a "perceptual" task and a "motor" task --
      were performed by right brain-damaged (RBD) patients with left hemispatial
      neglect, RBD patients without signs of neglect and control subjects. The
      perceptual task consisted of lateralized visual stimuli and central motor
      responses, whereas the motor task consisted of visual stimuli presented on the
      vertical midline and hand responses to be produced in either hemispace. Neglect
      patients showed a rightward bias on the perceptual task, but only two RBD
      patients (showing no signs of severe neglect) were consistently slowed in
      producing leftward motor responses. Different reference frames may thus be used
      in perceptual tasks and tasks involving arm movements. We conclude that
      hemispatial neglect commonly results from attentional impairments operating upon
      a visual perceptual frame of reference; additional deficits appear to be
      necessary to produce a directional motor disorder.

PMID- 9622189
TI  - Multiple-domain dissociation between impaired visual perception and preserved
      mental imagery in a patient with bilateral extrastriate lesions.
AB  - A brain-damaged patient is described whose pattern of performance provides
      insight into both the functional mechanisms and the neural structures involved in
      visual mental imagery. The patient became severely agnosic, alexic, achromatopsic
      and prosopagnosic following bilateral brain lesions in the temporo-occipital
      cortex. However, her mental imagery for the same visual entities that she could
      not perceive was perfectly preserved. This clear-cut dissociation held across all
      the major domains of high-level vision: object recognition, reading, colour and
      face processing. Our findings, together with other reports on domain-specific
      dissociations and functional brain imaging studies, provide evidence to support
      the view that visual perception and visual mental imagery are subserved by
      independent functional mechanisms, which do not share the same cortical
      implementation. In particular, our results suggest that mental imagery abilities
      need not be mediated by early visual cortices.

PMID- 9622190
TI  - Neglect syndrome for aversive stimuli in a macaque monkey with dorsomedial
      frontal cortex lesion.
AB  - After a session of unit activity recording, one of our monkeys presented an
      epileptic attack, which provoked contralateral tilting movements. The following
      days, the animal performed saccades and fixation tasks correctly in all
      directions, while contralateral arm reaching movements were severely impaired. To
      establish if the neurological lesion had changed the orienting performance we
      considered two types of stimuli, pleasant and aversive. Pleasant stimuli,
      presented in the ipsilateral or contralateral hemifield, readily drew the
      attention of the animal. If the same stimuli were presented simultaneously in
      both hemifields, the monkey oriented itself only toward the ipsilateral one.
      Aversive stimuli evoked an aggressive reaction only when the stimulus was
      localized in the ipsilateral hemifield. The animal clearly neglected the aversive
      stimulus presented in the contralateral hemifield. The animal recovered
      completely in 30 days. The postmortem examination revealed a lesion in the
      dorsomedial frontal cortex. The combined attentional and motor deficits suggest
      that this area may be involved in the preparation and execution of movements
      triggered by the affective meaning of the stimulus.

PMID- 9622191
TI  - Memory after frontal/temporal disconnection in monkeys: conditional and non
      conditional tasks, unilateral and bilateral frontal lesions.
AB  - Seven Cynomolgus monkeys (Macaca fascicularis) learned a series of reward-visual
      conditional discrimination problems, in which the arrival or non-arrival of a
      food pellet at the beginning of each trial acted as an instruction cue,
      signalling which of two visually distinct stimulus objects the animal should
      choose on that trial in order to obtain a further food pellet reward. Following
      surgical removal of the ventrolateral prefrontal cortex in one hemisphere and the
      inferior temporal cortex in the contralateral hemisphere, combined with forebrain
      commissurotomy, the four operated animals were severely impaired at relearning
      this task. They were not impaired, however, in non-conditional visual
      discrimination learning. Extending the unilateral frontal lesion to include the
      ventromedial prefrontal cortex had no detrimental effect, nor did complete
      unilateral removal of the frontal cortex. In a third experiment, the operated
      animals underwent a further surgery to remove either ventrolateral, ventral or
      complete frontal cortex similar to that in the opposite hemisphere. Compared to
      their previous level of performance, the animals with bilateral ventrolateral
      prefrontal lesions were now mildly impaired and the animals with the bilateral
      lesion extended to the ventromedial cortex more severely impaired on the non
      conditional visual discrimination task. The bilaterally lobectomized animals were
      unable to relearn the task. We suggest that behaviour in visual learning tasks is
      controlled by cortical convergence upon subcortical structures, possibly by
      striatal efferents from both the visual cortex and frontal cortex, and that
      intrahemispheric convergence of these two efferents within the corpus striatum of
      one hemisphere could allow detailed control of visual choices by non-visual
      information, while subcortical interhemispheric transfer allows only less
      detailed, more general control.

PMID- 9622192
TI  - The functional emergence of prefrontally-guided working memory systems in four-
      to eight-year-old children.
AB  - The neural processes that underlie the functional emergence of human cognitive
      functions, particularly those associated with the prefrontal cortex (PFC), are of
      growing interest to developmental psychologists and neuroscientists.
      Specifically, working memory functions have been correlated with PFC activity in
      nonhuman primates and adult humans but have not been extensively studied in
      children. We examined the developmental emergence of functions involved in
      working memory through the use of the Cambridge Neuropsychological Test Automated
      Battery (CANTAB), a computerized battery of nonverbal visually-presented
      neuropsychological tests designed to dissociate frontal from temporal lobe
      behavioral functions. Participants were normal children, aged 4-8 (n = 181) and a
      small group of young adults (n = 24) who completed measures of Spatial Memory
      Span, Spatial Working Memory, the Tower of London planning task, Visual Pattern
      and Spatial Recognition tasks, and a Set-Shifting task. Findings indicate a
      general age-related progression in ability levels on frontal lobe tasks, with 4
      year-olds performing worse than 5- to 7-year-olds on all measures. Eight-year
      olds are superior to younger children in their ability to solve complex problems
      but have not yet reached adult levels of performance on the most difficult items
      of the Tower of London and Spatial Working Memory tasks. We conclude that the
      development of working memory functions proceeds dimensionally, starting with
      refinement of basic perceptual and sensorimotor functions and culminating with
      the physiological maturation of widespread neural networks that integrate complex
      processing demands inherent to working memory tasks.

PMID- 9622193
TI  - A lateralised grip strength test to evaluate unilateral nigrostriatal lesions in
      rats.
AB  - A modified grip strength meter was designed to enable the separate measurement of
      lateralised grip strength in the two forelimbs of rats, in order to allow
      assessment of deficits in animals with unilateral lesions and grafts within the
      basal ganglia. Unilateral 6-hydroxydopamine lesions of the dopaminergic
      nigrostriatal bundle induced a significant asymmetry, marked by an increased grip
      strength on the side contralateral to the lesion. Lesioned animals with
      additional implants of embryonic nigral cell suspensions into the dopamine
      denervated neostriatum showed a reduced (but not significant) deficit and did not
      differ from control performance. The lateralised nature of the deficit excludes
      explanation based on global activational changes; rather the unilateral deficit
      may provide a simple test of unilateral 'rigidity' in a widely used rodent model
      of Parkinson's disease.

PMID- 9622194
TI  - Nerve growth factor, beta3-adrenoceptor and uncoupling protein 1 expression in
      rat brown fat during postnatal development.
AB  - An analysis was made of the expression of nerve growth factor (NGF) mRNA and
      protein in the brown fat of rats at different ages, and the results compared with
      the expression of beta3-adrenoceptor and uncoupling protein 1 (UCP1). NGF, beta3
      adrenoceptor, and UCP1 messenger RNA and protein levels were measured by means of
      reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting in
      the brown fat of rats at different ages (from 20-day-old fetuses (E20) to 16
      month-old rats). During the perinatal period, NGF production increased and then
      declined to adult levels (which are comparable with fetal levels) by eight
      months, and remained stable thereafter. Relatively low levels of NGF were present
      in the brown fat of aged rats. Taken together, these results suggest that NGF may
      be responsible for regulating sympathetic innervation during the perinatal and
      adult periods.

PMID- 9622195
TI  - Influence of extracellular matrix proteins on membrane potentials and
      excitability in NG108-15 cells.
AB  - Previous studies have demonstrated that components of the extracellular matrix
      can induce neurite extension and cell adhesion in the neuroblastoma x glioma
      hybrid cell line, NG108-15. Using standard intracellular recording techniques, we
      examined the resting membrane potential (RMP) and membrane excitability of NG108
      15 cells differentiated under serum-free media with representative extracellular
      matrix (ECM) protein components as the substrate. Surfaces coated with collagen
      IV and a laminin-1 synthetic peptide induced a significantly (P < 0.05) more
      hyperpolarized RMP than control polystyrene surfaces. For example, after > or =8
      days in culture NG108-15 cells plated on polystyrene exhibited a RMP of -33.2+/
      0.8 mV (mean+/-SEM, n=158 cells) whereas cells cultured on the laminin-1 peptide
      C16 and collagen IV showed a RMP of -37.6+/-0.7 mV (n=157) and -37.5+/-1.5 mV
      (n=68), respectively. Furthermore, the proportions of cells on ECM substrates
      showing membrane excitability, i.e. evoked action potentials (APs) and the
      capability for regular firing, were significantly greater compared to those cells
      cultured on polystyrene. Among excitable cells cultured on the different
      substrates, characteristics of the action potentials, such as AP duration,
      amplitude, and the maximum rate of rise, dV/dtMAX, were examined in detail. While
      little or no differences were observed between polystyrene and the laminin-1
      peptide groups, significant differences in the AP parameters were apparent for
      collagen IV. For example, dV/dtMAX for polystyrene and the laminin-1 peptide C16
      were only 71.7+/-24.5 V/s (n=11) and 59.0+/-8.9 V/s (n=9), respectively, whereas
      cells cultured on collagen IV surfaces exhibited a dV/dtMAX reaching 156.1+/-22.0
      V/s (n=7). These data support a role for ECM components in the maintenance of the
      RMP and membrane excitability in NG108-15 cells.

PMID- 9622196
TI  - Changes in neuropeptide immunoreactivity in cultured adult mouse sensory neurons
      following methylmercury chloride treatments.
AB  - Changes in the neuropeptide expression of sensory neurons, related to functional
      modulation, have been widely reported both following physical injury in vivo, and
      after toxic insult in vitro and in vivo. The current immunocytochemical study
      aimed to monitor the neuropeptide status of neuronal cultures prepared from adult
      mouse dorsal root ganglia (DRG), and to ascertain whether changes occurred
      following treatments with 0.1-1 microM methylmercury (MeHg). Proportions of both
      substance P (SP) and calcitonin gene related peptide (CGRP) containing neurons
      increased significantly, and were maintained throughout the 24 h exposure period.
      In contrast the numbers of somatostatin (SOM)-ir neurons decreased. Substance P-
      and CGRP-ir neuron increases may be related to nociceptive responses, whereas the
      decreases in SOM containing neurons could reflect a differential loss in this
      subset of sensory neurons.

PMID- 9622197
TI  - Facilitation of responses to AMPA but not kainate by cyclothiazide in primate
      somatosensory thalamus.
AB  - This study examines the possibility of multiple ionotropic non-N-methyl-D
      aspartate (NMDA) receptors in the chief sensory nuclei of the primate thalamus.
      Cyclothiazide, an antagonist of rapid desensitization of non-NMDA receptors, is
      shown to produce a facilitation of responses to the synthetic agonist (+/-)-alpha
      amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) but not kainate or NMDA
      in cells of the ventral posterior lateral and medial thalamic nuclei in the
      anesthetized monkey. These differential effects suggest the presence of multiple
      ionotropic non-NMDA excitatory amino acid receptors in the primate ventral
      posterior (VP) thalamus. Cyclothiazide-sensitive excitatory amino acid receptors
      have important roles in mechanisms of plasticity and excitotoxicity in other
      neural systems and so may mediate similar mechanisms in the somatosensory
      thalamus.

PMID- 9622198
TI  - Expression of adenosine A2a receptor gene in rat dorsal root and autonomic
      ganglia.
AB  - The adenosine A2a receptors (A2aR) play an important role in the purinergic
      mediated neuromodulation. The presence of A2aR in the brain is well established.
      In contrast, little is known about their expression in the periphery. The purpose
      of this study was to investigate the expression of A2aR gene in the autonomic
      (otic, sphenopalatine, ciliary, cervical superior ganglia and carotid body) and
      in the dorsal root ganglia of normal rat. Hybridization histochemistry with S35
      labelled radioactive oligonucleotide probes was used. An expression of A2aR gene
      was found in the large neuronal cells of the rat dorsal root ganglia. The
      satellite cells showed no expression of A2aR gene. In the superior cervical
      ganglion, isolated ganglion cells expressed A2aR. In the carotid body clusters of
      cells with a strong A2aR gene expression were found. In contrast, the ciliary and
      otic ganglia did not expressed A2aR gene, and only few small sized A2aR
      expressing cells were demonstrated in the sphenopalatine ganglion. The discrete
      distribution of A2aR gene expression in the peripheral nervous system speaks for
      a role of this receptor in the purinergic modulation of sensory information as
      well as in the sympathetic nervous system.

PMID- 9622199
TI  - Different effects of phospholipase A2 on agonist binding to hippocampal, cortical
      and recombinant homomeric alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate
      receptors.
AB  - Secretory phospholipase A2 (sPLA2) has been reported to modulate agonist and
      antagonist binding to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)
      receptors. Here we report that in hippocampal membranes sPLA2 increases the
      affinity of [3H]AMPA binding whereas in cortical membranes the affinity of
      binding is decreased. To test whether these results are due to the interaction of
      sPLA2 with different AMPA receptor subunits we used membranes from BHK cells
      expressing homomeric GluR1, GluR2 or GluR4 receptors. Pretreatment with the
      enzyme had no effect on [3H]AMPA binding to any of the homomeric receptors. We
      interpret these data to suggest that sPLA2 does not act directly at the AMPA
      receptor. Instead, sPLA2 may interact with a receptor-associated protein present
      in brain but not in BHK cells and this interaction may exert different effects in
      cortex and hippocampus.

PMID- 9622200
TI  - Effects of central leptin administration on blood pressure in normotensive rats.
AB  - We tested the hypothesis that intracerebroventricular (i.c.v.) administration of
      leptin would increase mean arterial pressure (MAP) in ad libitum (AL) fed and
      food deprived (FD) normotensive rats. Male Sprague-Dawley rats were chronically
      instrumented with a guide cannula directed at the lateral ventricle and a carotid
      arterial catheter. Following recovery from surgery, the MAP and heart rate (HR)
      response to i.c.v. administration of vehicle (5 microl saline over 1 min) or
      leptin (0.3 microg or 3.0 microg in 5 microl saline) were determined in
      conscious, unrestrained AL fed (n=7-10) and 48-h FD (n=5-10) rats. Food
      deprivation significantly reduced MAP (AL=116+/-3; FD=104+/-3 mmHg; P < 0.01)
      without altering HR. In AL rats, high dose leptin (3.0 microg, i.c.v.) produced a
      significant increase in MAP when maximal responses were evaluated (9+/-2 mmHg; P
      < 0.05), but did not significantly alter MAP and HR over time during the 90 min
      measurement period. In FD rats, low dose leptin (0.3 microg, i.c.v.) produced
      significant elevations in MAP (7+/-3 mmHg) after a latency of 60 min, while high
      dose leptin (3.0 microg, i.c.v.) produced an increase in MAP within the first 10
      min (10+/-3 mmHg) followed by an additional increase 1 h after injection (6+/-2
      mmHg). Leptin administration also produced delayed increases in HR in FD rats
      (0.3 microg, 34+/-5 b.p.m.; 3.0 microg, 57+/-10 b.p.m). These results indicate
      that leptin may modulate cardiovascular function through central mechanisms and
      may do so to a greater extent in food deprived animals.

PMID- 9622201
TI  - The effect of aging on the response of striatal preproenkephalin and
      preprotachykinin mRNA contents to chronic haloperidol treatment in rats:
      measurement by solution-hybridization RNase protection assay.
AB  - The preproenkephalin (PPeK) and preprotachykinin (PPT) mRNA contents in 3-, 10-
      and 23-month-old rats in the striatum were measured by solution hybridization
      RNase protection assay after 3 weeks of haloperidol injection. Haloperidol
      increased striatal PPek mRNA. There was no age-related difference in the response
      of striatal PPeK mRNA to chronic haloperidol treatment. The PPT mRNA decreased by
      21% after the haloperidol treatment in young rats only. Meanwhile, age decreased
      the PPT mRNA by 27 and 24% in 10- and 23-month-old rats, respectively. It is
      concluded that there is a difference in the effects of aging on the response of
      PPek and PPT mRNA contents to haloperidol and that the loss of PPT mRNA response
      in 10- and 23-month-old rats might be due to the change of dopamine system of the
      striatum in these rats.

PMID- 9622203
TI  - MK 801 and dexamethasone reduce both tumor necrosis factor levels and infarct
      volume after focal cerebral ischemia in the rat brain.
AB  - Focal cerebral ischemia in rats produces elevated levels of tumor necrosis factor
      (TNF)alpha in the ischemic brain region. To better understand the modulation of
      TNF during brain ischemia processes we carried out studies in a model of
      permanent middle cerebral artery occlusion (MCAo) in the rat. In non-treated
      ischemic animals, the maximum expression of TNF was observed at 12 h (246.1+/-33
      U/g) in the ischemic cortex and declined reaching near zero levels 24 h after
      MCAo. Given 10 min after MCAo, MK 801 (3 mg/kg, i.p.), a non-competitive NMDA
      receptor antagonist, exerted significant neuroprotection as measured by 47%
      reduction of total volume of infarction (P < 0.01 vs. ischemic-control). At the
      high dose of 3 mg/kg i.p., dexamethasone (DEX), which is known to reduce brain
      edema, decreased infarct size by 50% (P < 0.01 vs. ischemic-control). Both MK 801
      and DEX reduced TNF production in the ipsilateral cortex of ischemic animals by
      61 and 73%, respectively (P < 0.01 vs. ischemic-control). The data indicate that
      TNF levels increase after brain infarction, whereas they are reduced by
      neuroprotective agents, such as MK 801 and DEX, which act on different cellular
      levels.

PMID- 9622202
TI  - Proteolysis of highly polysialylated NCAM by the tissue plasminogen activator
      plasmin system in rats.
AB  - Tissue-type plasminogen activator (tPA), a serine protease which converts the
      zymogen plasminogen to the active protease plasmin, is believed to regulate
      neurite extension and neural cell migration by modulating extracellular
      metabolism. The highly polysialylated form of the neural cell adhesion molecule
      (NCAM-H) is strongly expressed in the developing brain and is believed to play a
      role in organizing the neural network. In this report, we incubated neonatal rat
      brain homogenates with human tPA and rat plasminogen in order to determine
      whether NCAM-H would be degraded. NCAM-H was degraded by plasmin which was formed
      from rat plasminogen by human tPA. The degradation was inhibited by the addition
      of plasminogen activator inhibitor type 1 (PAI-1) or aprotinin. These results
      suggest a possible contribution of the tPA-plasmin system to NCAM-H turnover in
      the developing brain.

PMID- 9622204
TI  - The relative contribution of constitutive and inducible cyclooxygenase activity
      to lipopolysaccharide-induced prostaglandin production by primary cultures of rat
      hypothalamic astrocytes.
AB  - In this study, we have compared the time-course effects of lipopolysaccharide
      (LPS) and interleukin-1beta on prostaglandin (PG) production by primary cultures
      of rat astrocytes. At variance with interleukin-1beta, LPS produced significant
      increases in PGE2 release after only 1 h of incubation, an effect unlikely to
      depend on new protein synthesis; the involvement of constitutive cyclooxygenase
      (COX-1) was therefore investigated. Experiments with acetylsalicylic acid showed
      that 80% of PGE2 production after 1 h of treatment with LPS is accounted for by
      COX-1; this figure decreases to about 30% after a 24-h treatment. The increase in
      PGE2 production occurring after a 24-h challenge with the endotoxin seems to
      involve the activation of phospholipase A2. In fact, LPS-stimulated PGE2 release
      was significantly reduced by a peptide from the primary sequence of lipocortin-1,
      peptide Ac2-26, which was previously shown to inhibit phospholipase A2 in several
      in vitro models.

PMID- 9622205
TI  - Rat central ORL-1 receptor uncouples from adenylyl cyclase during membrane
      preparation.
AB  - Nociceptin/orphanin FQ is the endogenous agonist of the orphan receptor ORL-1. In
      this study, we sought to examine any possible regional differences of nociceptin
      binding using [125I]Tyr14-nociceptin, and of agonist induced inhibition of cAMP
      formation in membranes prepared from cerebrocortex, cerebellum and brainstem. The
      binding of [125I]Tyr14-nociceptin was concentration-dependent and saturable, with
      Bmax and pKd (pM) values of 179.7+/-15.3 fmol/mg protein and 10.26+/-0.09 (60.0),
      12.4+/-1.8 fmol/mg protein and 10.44+/-0.07 (37.0), 52.3+/-0.8 fmol/mg protein
      and 10.16+/-0.08 (74.0) in cerebrocortical, cerebella and brainstem membranes,
      respectively. In all preparations, nociceptin up to 1 microM failed to inhibit
      basal and forskolin stimulated cAMP formation. In all tissues forskolin
      stimulated and nabilone (acting at the central cannabinoid receptor) inhibited
      cAMP formation. Collectively these data report regional differences in ORL-1
      receptor expression and that these receptors uncouple during membrane
      preparation.

PMID- 9622206
TI  - Redistribution of glutathione in the ischemic rat retina.
AB  - We have studied the effect of ischemia on the cellular distribution of
      glutathione in the rat retina using immunocytochemical methods. Distinct degrees
      of ischemia were induced by varying the length of the post-mortem interval until
      fixation of the retina. In immediately fixed retinas, glutathione was confined
      exclusively to retinal Muller cells. In retinas fixed 5-10 min post-mortem,
      glutathione levels in Muller cells were reduced concomitant with incipient
      labeling in retinal neurons. Post-mortem intervals longer than 10 min resulted in
      strong labeling of neurons, particularly of retinal ganglion cells, whereas
      Muller cells were essentially devoid of immunoreactivity. Our data suggest
      transfer of glutathione from glia cells to neurons under ischemic conditions.
      Such a mechanism, utilizing the antioxidant properties of glutathione could be
      part of a glia-neuronal interaction contributing to the amelioration of oxidative
      stress and explain the high tolerance of the rat retina against
      ischemia/reperfusion injury.

PMID- 9622207
TI  - Giant input neurons of the mushroom body: intracellular recording and staining in
      the cockroach.
AB  - The mushroom body (MB) of the insect brain is critical to associative memory
      formation. Intrinsic neurons within the MB (called Kenyon cells, KCs) receive
      sensory signals from input neurons in the calyces. The calyces of the cockroach
      MB receive branches of four giant neurons (calycal giants, CGs) which exhibit
      gamma-aminobutyric acid (GABA)-like immunoreactivity. Here we examined the CGs by
      intracellular recording and staining. The CGs have dendritic arborizations in the
      lateral horn (lateral protocerebral lobe) and the neuropil anterior to the alpha
      and beta lobes (output neuropils of the MB); their terminal arborizations cover
      the entire calyces. The CGs exhibit a spontaneous and rhythmic burst of spikes,
      which are suppressed by olfactory, visual, tactile or air current stimulation.
      The CGs may facilitate, by disinhibition, the acquisition of sensory signals by
      the KCs when the insect is aroused by sensory stimuli.

PMID- 9622208
TI  - Altered hemostasis in pulmonary hypertension.
AB  - Pulmonary hypertension is characterized by increased pressure in the pulmonary
      circulation and, in some cases, inflammation. Significant vascular remodeling
      occurs in response to these stresses and histopathology demonstrates in-situ
      thrombosis in a significant number of cases. Elevated shear stresses and
      inflammation, based on in-vitro data, would be expected to enhance platelet
      activation and aggregation/adhesion, increase release of von Willebrand factor,
      increase tissue factor expression, downregulate surface thrombomodulin with
      diminished thrombin inactivation and decreased protein C activation, and alter
      fibrinolytic factors with a net loss of fibrinolysis. Data from animal and human
      studies of pulmonary hypertension provide evidence for increased platelet
      activation, decreased platelet survival, increased release of von Willebrand
      factor antigen without an increase in activity, decreased soluble thrombomodulin
      and a net loss of fibrinolytic activity with excessive release of plasminogen
      activator inhibitor-1. These changes may result in in-situ thrombosis, which may
      occur as an inciting event of pulmonary hypertension, or as a consequence of
      other initiating factors. Chronic anticoagulation has been used in pulmonary
      hypertension based on observations of increased survival. However, the direct
      link between altered coagulation and the development or persistence of pulmonary
      hypertension awaits confirmation.

PMID- 9622209
TI  - Clinical experience with recombinant factor VIIa.
AB  - Recombinant factor VIIa (rFVIIa) represents a major therapeutic advance in the
      treatment of haemophilia patients with inhibitors. The efficacy and safety of
      rFVIIa has been extensively studied in over 1900 surgical and non-surgical
      bleeding episodes in over 400 patients with haemophilia A or B (with or without
      inhibitors) or acquired haemophilia. Of 103 evaluable surgical bleeding episodes,
      the response to treatment with rFVIIa was considered to be either excellent or
      effective in 81%, 86% and 92% of major, minor and dental bleeding episodes,
      respectively. Treatment has been evaluated in 518 serious bleeding episodes and
      the response was considered either excellent or effective in 62% of muscle, 80%
      of ear, nose and throat, 88% of central nervous system, 76% of joint, and 75% of
      internal or retroperitoneal bleeding episodes. An excellent safety profile has
      also been demonstrated: of 1957 treatments with rFVIIa, only 16 serious adverse
      events have been reported that were considered to be possibly, but not
      necessarily, related to treatment.

PMID- 9622210
TI  - Haemostatic system activation and prediction of vascular events in patients
      presenting with stable peripheral arterial disease of moderate severity. Royat
      Study Group.
AB  - This study reports on the predictive value of some haemostatic factors
      [fibrinogen, factor VII and plasminogen activator inhibitor (PAI)], a marker of
      endothelial damage (soluble thrombomodulin) and several markers of haemostatic
      system activation (factor VIIa, prothrombin fragment 1+2, thrombin-antithrombin
      complexes and D-dimers) on the incidence of vascular events in male, non-diabetic
      patients with chronic ischaemia of the lower limbs. The patients (n=324) were
      recruited consecutively in the thermal resort of Royat, France. The low incidence
      of death from vascular causes during the 2-year survey period (two patients) and
      the high percentage of former smokers (71%) indicated that this population of
      patients was affected by an arteriopathy of moderate intensity. After 2 years'
      follow-up, vascular events had occurred in 51 patients. The clinical and
      biological profiles did not differ significantly between patients with and
      without vascular events. However, the risk of vascular events during the 2 years
      of follow-up was significantly higher in those with high levels of PAI antigen
      and thrombin-antithrombin complexes. Thus, even in a population of patients with
      only moderately severe arteriopathy, high levels of thrombin-antithrombin
      complexes and PAI are predictive of vascular complications.

PMID- 9622211
TI  - Tissue factor pathway inhibitor and anti-FXa kinetic profiles of a new low
      molecular-mass heparin, Bemiparin, at therapeutic subcutaneous doses.
AB  - Low-molecular-mass heparins (LMMHs) exert an anti-FXa effect through antithrombin
      III (ATIII) and tissue factor pathway inhibitor (TFPI) displaced from endothelium
      and lipoproteins. This global anti-FXa potency is specific for different
      compounds. Whether these effects have a similar kinetic and duration is a matter
      of interest. We compared the kinetic profile of the TFPI effect (total and free)
      to the anti-FXa amidolytic activity induced by therapeutic subcutaneous doses of
      a new LMMH, Bemiparin. The overall kinetics of the anti-FXa amidolytic activity
      and the TFPI effect were different, TFPI achieving a maximal effect earlier than
      the anti-FXa activity and completely disappearing before it. The anti-FXa
      amidolytic activity of Bemiparin followed a linear dose-response pattern. Neither
      total nor free TFPI was directly proportional to the dose. At therapeutic
      subcutaneous doses, Bemiparin exerted an anti-FXa effect through TFPI during the
      first 2 h, through both ATIII and TFPI during the following 8 h (range 2-10 h)
      and through ATIII during the last 8 h (range 10-18 h).

PMID- 9622212
TI  - Factor X Frankfurt I: molecular and functional characterization of a hereditary
      factor X deficiency (Gla+25 to Lys).
AB  - A family with hereditary factor X deficiency is presented. One member, a 25-year
      old man, showed a mild bleeding tendency. His factor X activity (extrinsic: 56%;
      intrinsic: 55%; Russell's viper venom: 57%) and his level of circulating factor X
      antigen (55% of normal) were markedly reduced. Analysis of his factor X gene
      revealed a single point mutation within exon II resulting in the substitution of
      +25 Gla (GAA) by Lys (AAA). The mutation was determined by gene analysis to be
      heterozygous in this patient, his mother and one of his brothers. Clotting assays
      of factor X purified from the plasma of the index patient revealed an activity of
      89% of normal upon activation with Russell's viper venom, 77% of normal in the
      intrinsic and 81% of normal in the extrinsic coagulation pathway. The mutation
      responsible for the substitution of Lys for Gla+25 was introduced into an
      expression plasmid containing a wild type factor X cDNA and expressed in a
      mammalian cell line. Factor X antigen levels in the cell lysates and in the
      supernatant were identical in the mutant and wild type constructs. The specific
      activity of the factor X expressed from the mutant construct was 3% compared with
      the wild type construct. These data demonstrate that the substitution of Lys for
      Gla+25 results not only in a reduced level of factor X in the affected family
      members, but also in a substantial loss of specific factor X activity.

PMID- 9622213
TI  - Profibrinolytic properties characterize a stably transformed human endothelial
      cell line.
AB  - A stable immortalized venous endothelial cell (IVEC) line, obtained by
      transfection of human umbilical vein endothelial cells (HUVEC), retains many
      normal differentiated endothelial characteristics. We compared the fibrinolytic
      activities of IVEC and HUVEC, and observed that IVEC express a more
      profibrinolytic phenotype than HUVEC, since they bind and activate plasminogen
      more efficiently, produce more tissue plasminogen activator and urokinase-type
      plasminogen activator antigens, and secrete less plasminogen activator inhibitor
      1 antigen both under basal conditions and after stimulation with
      lipopolysaccharide, phorbol ester and tumor necrosis factor. Moreover,
      immunostaining and Western blotting of IVEC for the plasminogen/tissue
      plasminogen activator receptor annexin II, as well as Northern blotting of
      annexin II mRNA, revealed similar patterns of surface expression in IVEC and
      HUVEC. Plasminogen activator inhibitor-2 is expressed similarly in both cell
      types. IVEC may be a useful human model for functional and pharmacological
      explorations and modulations of fibrinolytic system components.

PMID- 9622214
TI  - Coagulation activation in patients with an inflammatory syndrome: is there a link
      with acquired protein S deficiency?
AB  - The pathogenic mechanisms of thrombosis during inflammatory syndromes are
      unknown. The aim of our study was to evaluate coagulation activation and
      fibrinolysis and to study an acquired protein S deficiency in 58 patients with an
      inflammatory syndrome of neoplastic (16), infectious (24) or systemic (18) origin
      and in 54 control subjects. The results indicated that coagulation activation,
      demonstrated by an increase in the prothrombin fragment 1+2, was present in
      patients with an inflammatory syndrome regardless of its origin. Free protein S,
      the only functionally active protein, was not reduced even though C4b-binding
      protein was increased in inflammatory syndromes. Thus, a prothrombotic state was
      found in inflammatory syndromes but is not explained by an acquired protein S
      deficiency. All except five patients had normal plasminogen activator inhibitor-1
      levels.

PMID- 9622215
TI  - Coexistence of antithrombin deficiency, factor V Leiden and hyperhomocysteinemia
      in a thrombotic family.
AB  - We report a thrombotic family with combined type I antithrombin deficiency and
      factor V Leiden (factor V-R506Q) in which the proposita, affected by recurrent
      venous and arterial thrombosis, was also characterized by mild
      hyperhomocysteinemia (28 micromol/l; normal <18.5 micromol/l). Her two thrombotic
      sisters, with normal antithrombin levels and factor V molecules, showed
      hyperhomocysteinemia (51 and 30 micromol/l, respectively). Four other members of
      the family had the combined antithrombin/factor V Leiden defect and two of them
      had thrombosis. The common A223V mutation in the methylenetetrahydrofolate
      reductase gene, responsible for the thermolabile variant of the enzyme, was found
      to be heterozygous in the proposita; the two sisters were homozygous and
      heterozygous, respectively. The heterozygous sister also had a high titre of
      antiphospholipid antibodies (85 units of immunoglobulin G antiphospholipid
      antibody/ml). Furthermore, low plasma folate levels were found in the three
      hyperhomocysteinemic subjects of the family. This family with several
      prothrombotic defects is a clear example of the polyfactorial nature of
      thrombophilia.

PMID- 9622216
TI  - A novel immunoassay for the quantification of human tissue factor binding to
      activated factor VII.
AB  - The binding of tissue factor to factors VII and VIIa (VII/VIIa) is the primary
      step for coagulation activation. Variants of human tissue factor leading to
      alterations in the binding to factor VII/VIIa have not been reported. We
      hypothesize that increased or decreased binding of tissue factor to factor VIIa
      might result in thrombosis and bleeding, respectively. The aim of this study was
      to establish an enzyme-linked immunosorbent assay to detect abnormalities in the
      binding of human tissue factor to recombinant factor VIIa (rVIIa). Tissue factor
      obtained from human monocytes was bound to rVIIa on microtiter wells in the
      presence of calcium. A murine antibody against human tissue factor and a
      biotinylated goat anti-mouse immunoglobuline were added. After incubation with
      streptavidin-horseradish peroxidase, colour development was measured using a
      chromogenic indicator system. Optimal assay conditions were obtained at tissue
      factor concentrations of 50-1500 pg/ml and rVIIa concentrations of 2.5 microg/ml.
      The binding of tissue factor to rVIIa was calcium-dependent and was inhibited by
      a monoclonal tissue factor antibody directed against the binding sites of tissue
      factor to rVIIa. The assay was evaluated in 23 healthy volunteers. Intra- and
      interassay variabilities were 3.9% and 10.2%, respectively. Among 22 subjects
      with unexplained bleeding and 47 patients with unexplained thrombosis, an
      individual with a decreased or increased binding of tissue factor to rVIIa could
      not yet be identified. In conclusion, this novel enzyme-linked immunosorbent
      assay can be used to detect and quantify an increased or a decreased binding of
      human tissue factor to rVIIa. Studies in patients indicate that, if such a defect
      exists, it is not a common cause of thrombosis or bleeding.

PMID- 9622217
TI  - An automated chromogenic peptide substrate assay for coagulation factor XII.
AB  - We have developed an automated chromogenic peptide substrate assay for factor XII
      (FXIIcs) on a Cobas Mira S Plus clinical chemistry analyser using a new
      commercially available kit. This was used to determine factor XII (FXII) levels
      in plasma samples from 320 blood donors, 206 patients with a history of venous
      thrombosis and 74 lupus anticoagulant positive (LA+) patients. Results were
      compared with those obtained in a clotting assay for FXII (FXIIct) and an
      immunochemical assay (FXIIag). A satisfactory correlation coefficient of 0.92 and
      a regression line equation of y = 7.898 + 0.871x was obtained between FXIIcs and
      FXIIct in the 320 blood donors. Levels of FXII below the calculated normal range
      were found in nine blood donors (2.8%) and 16 venous thrombosis patients (7.8%).
      The blood donors and patients with venous thrombosis with low FXIIcs values had
      FXII levels below our lower limits of normal for both FXIIct and FXIIag; all were
      lupus anticoagulant negative. When FXII levels were determined in the 74 LA+
      patients, 27 (36.5%) gave markedly lower FXII values in the FXIIct when compared
      with the FXIIcs. FXIIag levels corresponded with FXIIcs. The automated FXIIcs
      assay is therefore lupus anticoagulant insensitive and allows us to measure FXII
      levels accurately and routinely in large numbers of patient samples.

PMID- 9622218
TI  - The coagulation profile in hepatosplenic schistosomiasis.
AB  - The biological activity of blood coagulation factors II, V, VII, VIII, IX, X, XI
      and XII, fibrinogen and prekallikrein was assessed in 15 healthy subjects and 60
      patients with endemic Egyptian hepatosplenomegaly. The degree of liver disease
      was graded according to the Child-Pugh classification, the intensity of S.
      mansoni infection was monitored by determination of circulating schistosome
      immune complexes (CSIC) level using a monoclonal antibody and hemostasis
      activation was detected by measurement of hemostatic markers D-dimer and
      prothrombin fragment 1 + 2 (F1+2). Functional activity of antithrombin III,
      alpha2-antiplasmin and protein C as well as quantitative determination of plasma
      concentrations of alpha1-antitrypsin, C1 activator inhibitor and alpha2
      macroglobulin were also carried out. The progressive deterioration of liver
      function which matched the severity of the disease and the intensity of
      schistosomal infection led to a reduction in anticoagulant proteins (decreases in
      antithrombin III and protein C) resulting in hypercoagulability and thrombin
      generation (increased F1+2) subsequently followed by consumption (prolongation of
      coagulation screening tests, thrombocytopenia, hypofibrinogenemia and decreased
      factor VIII resulting in hypocoagulability and secondary fibrinolysis (increased
      D-dimer and decreased alpha2-antiplasmin). A significant decline in fibrinogen
      and factors VII, XII and prekallikrein was detected in bleeders compared with
      ascitic patients. The decline in factor XII was closely related to CSIC high
      titers in all disease groups, but was not correlated to D-dimer or F1+2
      concentrations. This suggests that circulating schistosome immune complexes may
      exert an inhibitory effect on contact factor XII which should be taken into
      account when considering the reasons for schistosomal coagulopathy and bleeding
      in hepatosplenic schistosomiasis.

PMID- 9622219
TI  - Familial lupus anticoagulant: a case report and review of the literature.
AB  - The antiphospholipid antibody (APLA) syndrome is defined by the presence of a
      lupus anticoagulant or markedly elevated plasma levels of anticardiolipin
      antibodies (ACAs), associated with venous or arterial thromboembolic events,
      fetal loss or thrombocytopenia. Familial clustering of raised APLA levels has
      been described, but the reports are heterogeneous with regard to the
      characterization of the APLA syndrome, coexisting autoimmune diseases and
      clinical complications. We describe two siblings with a lupus anticoagulant,
      elevated ACA-immunoglobulin G levels and systemic lupus erythematosus or related
      autoimmune disorders. Both patients experienced venous thrombotic complications
      at an early age. We provide a review of the literature, giving special
      consideration to the familial occurrence of lupus anticoagulants complicated by
      venous thrombosis, and emphasize the importance of family screening.

PMID- 9622220
TI  - Plasminogen activator inhibitor-1 promoter 4G/5G genotype is not a risk factor
      for myocardial infarction in a Japanese population.
AB  - There is little question that the blood clotting process is triggered and causes
      the vascular occlusion associated with myocardial infarction. Although it is less
      clear what part blood coagulation events might play in the etiology of coronary
      artery disease, impaired regulation of anticoagulation or fibrinolysis might be
      involved. Among anticoagulant and fibrinolytic factors, an elevated plasma
      plasminogen activator inhibitor-1 (PAI-1) concentration has been identified as a
      risk factor for the development of myocardial infarction. An association between
      one polymorphism of the PAI-1 promoter (4G/5G single nucleotide deletion/
      insertion at position -675) and plasma PAI-1 levels was described in 1995.
      However, most recent studies seem to point to the lack of such an association.
      This is the first report on the frequency of this polymorphism in the Japanese
      population with respect to the risk of myocardial infarction. Sixty-six patients
      with myocardial infarction and sixty-two healthy control patients were chosen for
      the analysis of the PAI-1 promoter 4G/5G genotype with polymerase chain reaction
      single strand conformation polymorphism. Five myocardial infarction patients and
      six in the control group were homozygous for the 4G/4G genotype. Twenty-eight and
      27 4G/5G and 33 and 29 5G/5G genotypes were found in myocardial infarction and
      control groups, respectively. The total frequencies of the 4G and 5G alleles were
      approximately 30% and 70% in both control and myocardial infarction groups. In
      conclusion, the PAI-1 promoter genotype is not a risk factor for myocardial
      infarction in the Japanese population. This is in contrast to the first report in
      Caucasians, suggesting an interaction with other genetic or environmental factors
      which influences the risk of myocardial infarction.

PMID- 9622221
TI  - Heparin cofactor II: a new marker for pre-eclampsia.
AB  - The plasma levels of heparin cofactor II were determined in pregnant women who
      were either normotensive, or had essential hypertension, gestational hypertension
      or pre-eclampsia during the third trimester and 72 h after delivery. Heparin
      cofactor II levels in the pre-eclampsia group were depressed. The clinical
      relevance of this finding is the potential utility of heparin cofactor II plasma
      levels in the differential diagnostic between non-proteinuric hypertension and
      pre-eclampsia.

PMID- 9622222
TI  - The 20210A allele of the prothrombin gene: a risk factor for juvenile stroke?
      Result of a pilot study.

PMID- 9622223
TI  - Typical mitral stenosis found in a systemic lupus erythematosus patient with a
      positive lupus anticoagulant. Is there a pathogenic link?

PMID- 9622224
TI  - Effects of aging on the dynamics of lymphocyte organ distribution in mice: use of
      a radioiodinated cell membrane probe.
AB  - We have employed a derivatized aminostyrylpyridinium dye, [125I]I2P-Di-6-ASP, to
      provide a relatively stable tag on mixed mouse splenocytes and purified B and T
      cells for the purpose of tracking the distribution of those cells among the
      organs of normal young (4 months) and aged (> 26 months) recipient mice. Cells
      from both young and aged donor spleens were studied. Special emphasis was placed
      on localization of donor cells in the spleens of the recipients because the
      majority of circulating lymphocytes localize in the spleen and the spleen is the
      principal organ of primary immune response. There was a profound difference in
      the efficiency of splenic acquisition of donor cells between young and aged
      recipients, a difference not found in the liver, lungs, kidneys or heart. In
      contrast young and old donor lymphocytes lodged equally well in the spleens of
      recipients of the same age. It was clear that the competence of the splenic
      microenvironment to serve as a lodging site for circulating lymphocytes
      deteriorated with age. Such a change could contribute significantly to the
      deficient immune response of aged subjects. We suggest that aging results in
      significant change in the splenic extracellular matrix to serve as an adhesive
      substratum for lymphocytes. Our data point to a need for detailed studies on age
      related changes in components of the extracellular matrix within lymphoid
      tissues. The novel compound which we employed for cell labeling is both
      radioactive and fluorescent and should be quite suitable for such studies.

PMID- 9622225
TI  - Effect of implantation of human apoAI gene on apoprotein composition and
      vasoactive properties of high-density lipoproteins in rats at different ages.
AB  - Transfer of human apoAI gene, within the molecular construction which provides
      its expression, to the liver of adult and aged rats resulted in the appearance of
      human protein in their blood, and was accompanied by changes in the content of
      high-density lipoproteins, as well as by the shifts in their protein and lipid
      composition. Administration of the human ApoAI gene was followed by changes of
      the vasoactive effects of HDL. Gene implantation is capable of enhancing the
      direct vasodilatory effects of HDL in old animals, being weakened by ageing, even
      against the background of normal age changes in the vascular wall tone.

PMID- 9622226
TI  - Cell kinetics of hemopoietic colony-forming units in spleen (CFU-S) in young and
      old mice.
AB  - The growth potential of the hemopoietic progenitor cells from young and old mice
      is similar. Previous studies of their cell-kinetics showed no significant
      differences between them when measured by the incorporation of tritiated
      thymidine ([3H]TdR). A different approach for exploring stem-cell kinetics in
      aged animals is provided by another method; the incorporation of
      bromodeoxyuridine (BrdUrd) during DNA synthesis followed by exposure to near
      ultraviolet light (near-UV) kills BrdUrd labelled cells in DNA-synthesis (S
      phase). This BrdUrd-near UV cytocide (BUUV) reveals the size of cycling fractions
      at the level of hemopoietic progenitor cells; it also demonstrates the velocity
      of the cells entering S-phase when cells are labeled by a continuous infusion of
      BrdUrd by an osmotic pump, followed by an appropriate colony-assay for each
      progenitor cell. We compared the cell kinetics of young and old hemopoietic
      progenitor cells (CFU-S) by this approach. Osmotic pumps were implanted
      subcutaneously in the backs of young (2 months) and old (22 months) male
      C57BL/6CrSlc mice for 2, 4, 8, 12, and 16 days to continuously infuse BrdUrd at a
      flow-rate of 1 mg/h per kg. Cells were harvested from femoral marrow of the
      infused mice, plated in non-coated bacterial plates, and exposed to a single dose
      of near-UV at 4000 J/m2. After BUUV cytocide, bone-marrow cells were assayed for
      8- and 13-day CFU-S colonies. In the 8-day colonies, the cytocide fraction of CFU
      S from young mice increased rapidly, whereas the fraction from old mice showed
      flatter curves. Both curves reached a plateau at 52.6% for young, and 43.9% for
      old mice, and then converged 4 days after labeling. In the 13-day colonies, the
      curve for the aged was much flatter than that for the young; however, the
      plateaus in both young and old are similar, but at much lower values than
      earlier, i.e. 24.5% and 16.0%, respectively. The size of the cycling fraction of
      progenitor cells was close in the two groups during the steady-state cell-cycle.
      However, the velocity of the cell cycle at a progenitor level was very different,
      old mice being much slower. Further, within the progenitors, the cell cycle was
      much slower in the primitive ones and became faster when the stem cells
      differentiated into mature progenitor cells.

PMID- 9622227
TI  - Adrenal neuropeptide Y mRNA but not preproenkephalin mRNA induction by stress is
      impaired by aging in Fischer 344 rats.
AB  - Relatively few molecular markers of stress have been studied in aged individuals.
      Interactions of age and stress on adrenal neuropeptide Y (NPY) and
      preproenkephalin (ppENK) expression have not been reported. The purpose of these
      studies was to characterize the adrenal NPY and ppENK responses to stress using a
      common stressor, physical restraint for 2 h, in Fischer 344 rats at 7, 16 and 23
      months of age. Northern blot techniques were used to evaluate induction by stress
      of adrenal NPY mRNA and adrenal ppENK mRNA. Two humoral responses to stress,
      serum glucose and corticosterone, were measured to corroborate that a stress
      response occurred. We observed that the induction by stress of adrenal NPY mRNA
      is impaired with age but the stress-induced elevation of adrenal ppENK mRNA,
      blood glucose, and corticosterone show no evidence of age-related impairments.

PMID- 9622228
TI  - Analysis of oxygen consumption and mitochondrial permeability with age in mice.
AB  - Biochemical and physiological parameters have been investigated in purified liver
      mitochondria from C57BL/6J mice of relatively young and old age, 1 month vs. 36
      months. Under identical purification conditions, mitochondria from old animals
      consumed significantly less O2 under state 3 conditions (i.e. with saturating ADP
      stimulation), consistent with a lower activity of the electron transport chain.
      In the absence of ADP (i.e. state 4 conditions), old mitochondria consumed
      significantly more O2 than young mitochondria; one possible explanation was
      increased mitochondrial permeability as a result of induction of the
      mitochondrial permeability transition (MPT), and this was investigated by the
      mitochondrial swelling assay. In response to induction by 20 microM Ca2+, MPT
      rates were observed to be variable, but significantly faster in old mitochondria
      (t1/2 = 105 s) than in young mitochondria (t1/2 = 155 s), and in all cases MPT
      was inhibitable by cyclosporin A (CsA). The implications of lower state 3
      respiration, higher state 4 respiration and increased rate of MPT in old
      mitochondria are discussed.

PMID- 9622229
TI  - Age-dependence of the lateral diffusion coefficient of Con-A receptor protein in
      the skeletal muscle membrane of C57BL/6J mice.
AB  - The lateral diffusion coefficient (Dp) of the Con-A receptor protein was measured
      in the sarcolemma of the quadriceps femoris (QF) muscle of male and female
      C57BL/6JNia mice in four age groups between 2 and 26 months. Freshly prepared, ex
      vivo taken muscle strips were stained with Con-A-FL conjugate for 10 min, and
      fluorescence recovery after photobleaching (FRAP) measurements were carried out
      on 20-30 cells per animal, at 37 degrees C. Using this technique, Dp, and the
      fractional recovery (mobile fraction = FR%) of these proteins can be measured. In
      the youngest male and female age groups, Dp values of 5.72E-10 and 5.43E-10
      cm2/s, and FR% values of 43.3 and 36.3%, were found, respectively. Dp displayed a
      characteristic, significant, negative, linear correlation with age in both sexes.
      The slope of the linear regression line calculated per month of age was 1.06E-11
      and 0.96E-11 cm2/s for males and females, respectively; both of them differ from
      zero highly significantly. FR% values tended to increase slightly with age, yet
      the estimated average Dp = D(FR), calculated for the total Con-A receptor pool,
      maintained its significant, negative, linear age-correlation. The physiological
      significance of these changes needs to be clarified in the future.

PMID- 9622230
TI  - Mitochondrial DNA in platelets from aged subjects.
AB  - This study aimed to assess platelets as a possible model for screening the
      accumulation of mitochondrial DNA mutations, particularly during normal ageing.
      For this purpose we isolated platelets from young and old donors selected by lack
      of systemic and haematological diseases. We studied the accumulation of a
      particular deletion (4977-bp deletion) that usually accumulates in an age-related
      manner in different post-mitotic tissues, such as brain, heart and skeletal
      muscle, and in some non-post-mitotic tissues (skin, liver). Using different
      primers, we failed to detect this particular species of deletion in platelets
      both from young and old individuals. However, we cannot exclude the presence of
      other species of deletions or point mutations affecting the mitochondrial DNA in
      platelets during the aging process.

PMID- 9622231
TI  - Aging, calorie restriction and ubiquitin-dependent proteolysis in the livers of
      Emory mice.
AB  - Calorie restriction (R), the only known method to delay the aging process and
      extend mean and maximal lifespan, has been shown to delay the age-related decline
      in protein degradation. There are several proteolytic pathways. The ubiquitin-
      and ATP-dependent proteolytic pathway (UPP) is frequently associated with
      degradation of damaged abnormal and/or regulatory proteins. We examined the
      effect of aging and R on supernatants of livers taken from young (4.5 months) and
      old (23 months) Emory mice. Aging was associated with increased levels of
      endogenous ubiquitin conjugates, enhanced ability to form high molecular weight
      conjugates and ubiquitin activating (E1) and ubiquitin conjugating (E2) activity
      in the control (C) liver supernatants. The age-related increase in levels of
      endogenous ubiquitin conjugates in liver appears to be primarily due to increased
      E1 and E2 activities. R prevented the age-related increase in E1 and E2 activity,
      and thus prevented the age-related increase in levels of ubiquitin conjugates. In
      spite of the age-related increase in ubiquitin conjugates, no age-related changes
      in ubiquitin-dependent proteolytic pathway were observed in the C animals. R was
      associated with an enhanced ability (130%) to degrade beta-lactoglobulin by the
      ubiquitin-dependent proteolytic pathway in livers from 4.5-month-old animals
      relative to age-matched C livers. However, rates of the ubiquitin-dependent
      degradation of beta-lactoglobulin in the 23-month-old C and R animals were
      indistinguishable. There were no age- or diet-related differences in the ability
      to degrade another substrate, oxidized ribonuclease (RNase).

PMID- 9622232
TI  - Extracellular levels of dopamine and its metabolite 3,4-dihydroxy-phenylacetic
      acid measured by microdialysis in the corpus striatum of conscious AS/AGU mutant
      rats.
AB  - The AS/AGU rat is a mutant derived from the Albino Swiss (AS) strain. It is
      characterized by an ungainly, staggering gait, hind limb rigidity, whole body
      tremor and, in older animals, difficulty in initiating movement. As and AS/AGU
      males aged three, six and nine months (n=6 per group) were used to estimate the
      levels of dopamine and its metabolites in the extracellular fluid of the caudate
      putamen. The results indicate a profound loss of dopamine in the extracellular
      fluid at all age points examined, together with an increase in the concentration
      of the metabolite 3,4-dihydroxyphenylacetic acid. It is suggested that these
      changes reflect a defect of dopaminergic neuron function which may underlie the
      motor disorder seen in these animals.

PMID- 9622233
TI  - Self-administration of the cannabinoid receptor agonist WIN 55,212-2 in drug
      naive mice.
AB  - Marijuana is one of the most widely used illicit recreational drugs. However,
      contrary to the majority of drugs abused by humans, there is a general opinion
      that rewarding effects are not manifested by animals. We studied a synthetic
      cannabinoid agonist WIN 55,212-2 using an intravenous self-administration model
      in drug-naive mice. The results of this study show that WIN 55,212-2 was
      intravenously self-administered by mice in a concentration-dependent manner
      according to a bell-shaped curve. Thus, self-administration of WIN 55,212-2
      significantly increased, with respect to the vehicle self-administration control
      group, at concentrations of 0.5 and 0.1 mg/kg per injection. However, at WIN
      55,212-2 concentration of 0.5 mg/kg per injection, self-administration
      significantly decreased. The results obtained show how WIN 55,212-2 is able to
      elicit both rewarding and aversive effects depending on the concentration used.
      Pretreatment of mice with the cannabinoid CB1 receptor antagonist SR 141716A
      (0.25 mg/kg, i.p.) completely prevented WIN 55,212-2 (0.1 mg/kg per injection)
      self-administration, indicating that WIN 55,212-2 rewarding effects are
      specifically mediated by cannabinoid CB1 receptors.

PMID- 9622234
TI  - Viewpoint: the core and matrix of thalamic organization.
AB  - The integration of the whole cerebral cortex and thalamus during forebrain
      activities that underlie different states of consciousness, requires pathways for
      the dispersion of thalamic activity across many cortical areas. Past theories
      have relied on the intralaminar nuclei as the sources of diffuse thalamocortical
      projections that could facilitate spread of activity across the cortex. A case is
      made for the presence of a matrix of superficially-projecting cells, not confined
      to the intralaminar nuclei but extending throughout the whole thalamus. These
      cells are distinguished by immunoreactivity for the calcium-binding protein, D28K
      calbindin, are found in all thalamic nuclei of primates and have increased
      numbers in some nuclei. They project to superficial layers of the cerebral cortex
      over relatively wide areas, unconstrained by architectonic boundaries. They
      generally receive subcortical inputs that lack the topographic order and
      physiological precision of the principal sensory pathways. Superimposed upon the
      matrix in certain nuclei only, is a core of cells distinguished by
      immunoreactivity for another calcium-binding protein, parvalbumin, These project
      in highly ordered fashion to middle layers of the cortex in an area-specific
      manner. They are innervated by subcortical inputs that are topographically
      precise and have readily identifiable physiological properties. The parvalbumin
      cells form the basis for sensory and other inputs that are to be used as a basis
      for perception. The calbindin cells, especially when recruited by corticothalamic
      connections, can form a basis for the engagement of multiple cortical areas and
      thalamic nuclei that is essential for the binding of multiple aspects of sensory
      experience into a single framework of consciousness.

PMID- 9622235
TI  - Interaction between dopamine and glutamate in the sensorimotor cortex during
      conditioned placing reaction.
AB  - Changes in impulse activity of sensorimotor cortex neurons associated with
      interaction of glutamate and dopamine during conditioned placing reaction were
      investigated in experiments on cats. Application of either glutamate or levodopa
      as a dopamine precursor increased background and evoked impulse activity in many
      of sensorimotor cortex neurons. It occurred occasionally that an increased
      impulse activity of cortical neurons produced by joint application of glutamate
      and levodopa could be much more intense than that produced by one of these
      substances. Amphetamine acted on cortical neurons in a similar way as levodopa.
      Haloperidol, a non-selective blocker of dopamine1 and dopamine2 receptors,
      increased or did not change background and evoked impulse activity in some
      cortical neurons. In contrast to application of glutamate alone, simultaneous
      application of glutamate and haloperidol to the neocortex depressed neuronal
      responses connected with conditioned movement. Thus, glutamate cannot exert its
      potentiating effect on evoked neuronal activity due to the depressing action of
      haloperidol. This means that glutamate potentiation is realized to a great extent
      through molecular mechanisms common for glutamate and dopamine, possibly through
      G-proteins which are common for glutamate metabotropic and dopamine receptors.

PMID- 9622236
TI  - Calbindin-D28k fails to protect hippocampal neurons against ischemia in spite of
      its cytoplasmic calcium buffering properties: evidence from calbindin-D28k
      knockout mice.
AB  - Cytoplasmic calcium-binding proteins are thought to shield neurons against damage
      induced by excessive Ca2+ elevations. Yet, in theory, a mobile cellular Ca2+
      buffer could just as well promote neuronal injury by facilitating the rapid
      dispersion of Ca2+ throughout the cytoplasm. In sharp contrast to controls, in
      mice lacking the gene for calbindin-D28k, synaptic responses of hippocampal CA1
      pyramidal neurons which are normally extremely vulnerable to ischemia, recovered
      significantly faster and more completely after a transient oxygen-glucose
      deprivation in vitro, and sustained less cellular damage following a 12 min
      carotid artery occlusion in vivo. Other cellular and synaptic properties such as
      the altered adaptation of action potential firing, and altered paired-pulse and
      frequency potentiation at affected synapses in calbindin-D28k-deficient mice were
      consistent with a missing intraneuronal Ca2+ buffer. Our findings provide direct
      experimental evidence against a neuroprotective role for calbindin-D28k.

PMID- 9622237
TI  - Hippocampal dynorphin B injections impair spatial learning in rats: a kappa
      opioid receptor-mediated effect.
AB  - The hippocampus plays a central role in the acquisition and storage of
      information. Long-term potentiation in the mossy fibre pathway to the CA3 region
      in the hippocampus, an animal model of memory acquisition, is modulated by
      dynorphin peptides. This study investigated the possible role of hippocampal
      dynorphin in spatial learning. Male rats were trained in the Morris Water Task
      after microinjection with different doses of dynorphin B (1, 3.3 or 10 nmol/rat)
      or artificial cerebrospinal fluid (as control) into the CA3 region of the dorsal
      hippocampus. Dynorphin B was found to impair spatial learning at all tested
      doses. The synthetic kappa1-selective opiate receptor antagonist nor
      binaltorphimine (2 nmol) also given into the hippocampus fully blocked the
      acquisition impairment caused by dynorphin B (10 nmol), while nor-binaltorphimine
      alone did not affect learning performance. These findings suggest that dynorphin
      peptides could play a modulatory role in hippocampal plasticity by acting on
      hippocampal kappa-receptors and thereby impair spatial learning.

PMID- 9622238
TI  - Kinetics of sevoflurane action on GABA- and glycine-induced currents in acutely
      dissociated rat hippocampal neurons.
AB  - Effects of a new kind of volatile anaesthetics, sevoflurane, on GABA- and glycine
      gated chloride current (ICl) were examined in single pyramidal neurons acutely
      dissociated from the rat hippocampal CA1 region, using the voltage-clamp mode of
      the nystatin-perforated patch-clamp technique. Rapid application of sevoflurane
      induced ICl by itself, with the time to peak reduced as the sevoflurane
      concentration was increased from 10(-3) to 3 x 10(-3) M. Although a pretreatment
      with 10(-3) M sevoflurane enhanced the peak amplitude of GABA (3 x 10(-6) M)
      induced ICl and suppressed the peak amplitude when the GABA concentration was
      increased to 10(-4) M, the pretreatment decreased the time to peak of the ICl
      induced by any concentration of GABA (from 3 x 10(-6) to 10(-4) M). The treatment
      also accelerated the decay phase of the GABA-induced ICl. On the other hand,
      sevoflurane suppressed the peak ICl induced by 3 x 10(-5) M glycine in a
      concentration-dependent manner. In the presence of 3 x 10(-4) M sevoflurane, the
      peak amplitude of the glycine-induced ICl was decreased without changes in EC50
      or Hill coefficients. Pretreatment with 10(-3) M sevoflurane did not affect the
      time to peak of the ICl induced by any concentration of glycine (from 3 x 10(-5)
      to 10(-3) M). Pretreatment with 3 x 10(-8) M strychnine markedly prolonged the
      time to peak of the glycine-induced ICl. These results suggest that sevoflurane
      modulated the amplitude of the GABA responses, depending on the balance of the
      accelerated activation and decay phases, and that sevoflurane suppressed the
      glycine-induced ICl in a non-competitive manner without noticeable effect on the
      kinetics. The reversible and differential modulation of GABA(A) and glycine
      receptors might underlie a part of the anaesthetic actions and less adverse
      clinical effects of sevoflurane.

PMID- 9622239
TI  - Inhibition of GABAergic inhibitory postsynaptic currents by cannabinoids in rat
      corpus striatum.
AB  - Electrophysiological consequences of activation of cannabinoid receptors have
      been mostly investigated on neuronal cell lines and on cells transfected with
      cannabinoid receptors. The aim of the present experiments was to study
      cannabinoid effects on identified neurons in situ. Electrically-evoked
      postsynaptic currents and voltage-dependent calcium currents were investigated in
      the principal neurons of the corpus striatum, the medium spiny neurons, with the
      patch-clamp method for brain slices. These neurons were chosen because they
      produce messenger RNA for cannabinoid receptors and because the density of
      cannabinoid binding sites in the striatum is high. Activation of muscarinic
      receptors by carbachol (10(-5) M) reduced inhibitory postsynaptic current
      amplitude by 67%. The synthetic cannabinoid receptor agonist R(+)-[2,3-dihydro-5
      methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4- benzoxazin-yl]-(1
      naphtalenyl)methanone (WIN55212-2; 10(-8) to 10(-5) M) dose-dependently reduced
      striatal inhibitory postsynaptic currents; the maximum effect, inhibition by 52%,
      was observed at 10(-6) M. Another cannabinoid agonist, (-)-cis-3-[2-hydroxy-4
      (1,1-dimethylheptyl)phenyl]-trans-4-(3-hydr oxypropyl)cyclohexanol (CP55940; 10(
      6) M), also reduced inhibitory postsynaptic currents, by 50%. The CB1
      cannnabinoid receptor antagonist N-piperidino-5-(4-chlorophenyl)-1-(2,4
      dichlorophenyl)4-methyl-3-pyra zolecarboxamide (SR141716A; 10(-6) M) had no
      effect when given alone but abolished the effect of WIN55212-2 (10(-6) M).
      WIN55212-2 (10(-6) M) did not change the current evoked by the GABA(A)-receptor
      agonist muscimol (10(-6) M). Activation of muscarinic receptors by carbachol (10(
      5) M) inhibited voltage-dependent calcium currents by 21%, but the cannabinoid
      receptor agonist WIN55212-2 (10(-6) M) was without effect. The results show that
      activation of CB1 cannabinoid receptors reduces GABAergic inhibitory postsynaptic
      currents in medium spiny neurons of the corpus striatum: the likely mechanism is
      presynaptic inhibition of GABA release from terminals of recurrent axons of the
      medium spiny neurons themselves.

PMID- 9622240
TI  - Dopamine turnover and metabolism in the striatum of parkinsonian rats grafted
      with genetically-modified human astrocytes.
AB  - The potential of a novel therapeutic approach for treating Parkinson's disease,
      which involves the transplantation of a transfected human astrocyte cell line SVG
      TH, that stably expresses the rate-limiting enzyme for dopamine production,
      tyrosine hydroxylase, was examined. SVG-TH and untransfected parent cells were
      grafted into the diseased striatum of rats in which Parkinson's disease had been
      induced by the administration of 6-hydroxydopamine. The in situ production and
      spillover of 3,4-dihydroxyphenylalanine (the precursor of dopamine), dopamine and
      their metabolites in the striatal extracellular fluid of the grafted rats was
      determined in conscious animals using the microdialysis technique and a high
      pressure liquid chromatography apparatus. Alleviation of symptoms of Parkinson's
      disease (abnormal movements) was evaluated by rotation tests. Upon
      transplantation of the SVG-TH cells into the striatum of the parkinsonian rats,
      the levels of dopamine in extracellular fluid of the striatum reached those of
      the normal rats, and correlated well with the improvement (74%) in their rotating
      behaviour (behavioural deficit). The levels of the two main dopamine metabolites,
      dihydroxyphenylacetic acid and homovanillic acid, were low in the lesioned rats,
      even after SVG-TH transplantation. An alternative route of metabolism of dopamine
      may occur in the transplanted striatum, since the dopamine metabolite, 3-O
      methoxy-4-hydroxy-phenylethylamine, appeared, which indicates activity of
      catechol-O-methyl transferase. Upon blockade of L-aromatic-amino acid
      decarboxylase, 3,4-dihydroxyphenylalanine accumulated in extracellular fluid of
      the 6-hydroxydopamine-lesioned and SVG-TH-grafted rats, which indicated that
      these cells produced active tyrosine hydroxylase in vivo. These findings indicate
      the potential of treating Parkinson's disease by the intrabrain grafting of human
      astrocyte cells transfected with the rate limiting enzyme for dopamine
      production.

PMID- 9622241
TI  - Enhanced morphine-induced behavioural effects and dopamine release in the nucleus
      accumbens in a transgenic mouse model of impaired glucocorticoid (type II)
      receptor function: influence of long-term treatment with the antidepressant
      moclobemide.
AB  - In vivo microdialysis experiments were conducted in transgenic mice with impaired
      glucocorticoid receptor function resulting from expression of antisense directed
      against glucocorticoid receptor messenger RNA. Basal corticosterone and serotonin
      levels in the nucleus accumbens of untreated transgenic mice were enhanced
      compared to control mice (B6C3F1). Following a systemic morphine injection (15
      mg/kg) mesolimbic dopamine and serotonin release was markedly increased in
      transgenic mice compared to control mice and in parallel enhanced behavioural
      stimulation was observed in these animals. After pretreatment with the
      antidepressant moclobemide over a time period of eight weeks (15 mg/kg/day)
      elevated basal levels of both corticosterone and serotonin were normalized in
      transgenic mice. Furthermore, morphine-induced dopamine and serotonin release as
      well as behavioral stimulation were suppressed in transgenic mice and similar to
      that in control mice. The results indicate that impaired glucocorticoid receptor
      function influences the basal release of serotonin in the nucleus accumbens. This
      alteration has no effect on basal but on morphine-stimulated release of dopamine
      in the mesolimbic system. An enhanced sensitivity to the effects of morphine is
      apparently related to elevated brain corticosterone and serotonin levels and can
      be normalized by long-term antidepressant treatment.

PMID- 9622242
TI  - Strychnine-sensitive glycine responses in neurons of the lateral amygdala: an
      electrophysiological and immunocytochemical characterization.
AB  - Electrophysiological and staining techniques in the in vitro slice preparation of
      the rat and guinea-pig lateral amygdala were combined with immunocytochemical
      approaches, in order to characterize the neuronal substrate, the ionic basis and
      the pharmacological properties of glycine-mediated responses, and to map the
      distribution and composition of the mediating glycine receptors. Glycine was
      locally applied to spiny, pyramidal-like cells in the lateral amygdala, which
      possessed electrophysiological properties typical of projection neurons. Glycine
      induced a membrane hyperpolarization from rest and associated decrease in input
      resistance, and an interruption of spike firing and calcium-mediated high
      threshold oscillations. The glycine-mediated response persisted during blocked
      synaptic transmission, reversed close to the presumed somatic chloride
      equilibrium potential and shifted during altered transmembrane Cl- gradients as
      expected for an increase in membrane chloride conductance. Responses to glycine
      were reversibly blocked by strychnine, but were insensitive to picrotoxin and
      bicuculline. Strychnine-sensitive components of spontaneous activity, but not of
      evoked synaptic responses, were frequently observed. Similar responses to glycine
      occurred in neurons of the guinea-pig and rat lateral amygdala, as well as in the
      central amygdala. The localization and composition of glycine receptors were
      examined through the use of monoclonal antisera directed against the binding
      protein (gephyrin), the alpha1 subunits (mAb2b) and alpha/beta subunits (mAb4a)
      of glycine receptors. A dense to moderate immunostaining for gephyrin was
      observed throughout the amygdaloid complex, whereas mAb4a immunofluorescent
      neurons, displaying strong punctate labelling around the soma and proximal
      dendrites, were confined to the lateral amygdala. No immunoreactivity was
      obtained with mAb2b antibodies in the amygdala. It is concluded that pyramidal
      like projection cells in the lateral amygdala express functional glycine
      receptors at somatic and proximal dendritic sites, which are composed of beta and
      alpha subunits other than the alpha1 type, and which may play a functional role
      in the control of excitatory activity in the amygdala, particularly during
      periods of decreased GABAergic influence.

PMID- 9622243
TI  - Sprouting of primary afferent fibers after spinal cord transection in the rat.
AB  - After spinal cord injury, hyper-reflexia can lead to episodic hypertension,
      muscle spasticity and urinary bladder dyssynergia. This condition may be caused
      by primary afferent fiber sprouting providing new input to partially denervated
      spinal interneurons, autonomic neurons and motor neurons. However, conflicting
      reports concerning afferent neurite sprouting after cord injury do not provide
      adequate information to associate sprouting with hyper-reflexia. Therefore, we
      studied the effect of mid-thoracic spinal cord transection on central projections
      of sensory neurons, quantified by area measurements. The area of myelinated
      afferent arbors, immunolabeled by cholera toxin B, was greater in laminae I-V in
      lumbar, but not thoracic cord, by one week after cord transection. Changes in
      small sensory neurons and their unmyelinated fibers, immunolabeled for calcitonin
      gene-related peptide, were assessed in the cord and in dorsal root ganglia. The
      area of calcitonin gene-related peptide-immunoreactive fibers in laminae III-V
      increased in all cord segments at two weeks after cord transection, but not at
      one week. Numbers of sensory neurons immunoreactive for calcitonin gene-related
      peptide were unchanged, suggesting that the increased area of immunoreactivity
      reflected sprouting rather than peptide up-regulation. Immunoreactive fibers in
      the lateral horn increased only above the lesion and in lumbar segments at two
      weeks after cord transection. They were not continuous with dorsal horn fibers,
      suggesting that they were not primary afferent fibers. Using the fluorescent
      tracer DiI to label afferent fibers, an increase in area could be seen in
      Clarke's nucleus caudal to the injury two weeks after transection. In conclusion,
      site- and time-dependent sprouting of myelinated and unmyelinated primary
      afferent fibers, and possibly interneurons, occurred after spinal cord
      transection. Afferent fiber sprouting did not reach autonomic or motor neurons
      directly, but may cause hyper-reflexia by increasing inputs to interneurons.

PMID- 9622244
TI  - A quantitative study of neurons which express neurokinin-1 or somatostatin sst2a
      receptor in rat spinal dorsal horn.
AB  - The neurokinin-1 and somatostatin sst2a receptors have both been identified on
      spinal cord neurons. In this study we have estimated the proportions of neurons
      in different parts of the spinal cord which express these receptors, by using a
      monoclonal antibody against a neuronal nuclear protein named NeuN and combining
      the optical disector method with confocal microscopy. The NeuN antibody was
      initially tested on over 3200 neurons identified with antisera against a variety
      of compounds, including neuropeptides, enzymes and receptors, and also on
      astrocytes and oligodendrocytes. All of the neurons, but none of the glial cells
      that were examined possessed NeuN-immunoreactivity, which suggests that NeuN is a
      reliable marker for all spinal cord neurons. We found that approximately 45% of
      neurons in lamina I, 23-29% of those in laminae IV-VI and 18% in lamina X
      possessed the neurokinin-1 receptor, while the receptor was present on a smaller
      proportion of neurons in laminae II and III (6% and 11%, respectively). Thirteen
      percent of lamina I neurons and 15% of those in lamina II expressed the sst2a
      receptor. To provide further information about the types of neuron which possess
      the sst2a receptor, we searched for possible co-existence with the neurokinin-1
      receptor as well as with GABA and glycine. sst2a and neurokinin-1 receptors were
      not co-localized on neurons in laminae I and II. All of the sst2a-immunoreactive
      neurons examined were also GABA-immunoreactive, and 83.5% were glycine
      immunoreactive, indicating that the receptor is located on inhibitory neurons in
      the superficial dorsal horn. These results demonstrate the proportions of neurons
      in each region of the spinal cord which can be directly activated by substance P
      or somatostatin acting through these receptors. Levels of receptors can change in
      pathological states, and this method could be used to determine whether or not
      these changes involve alterations in the number of neurons which express
      receptors. In addition, the method can be used to estimate the sizes of
      neurochemically-defined populations of spinal cord neurons.

PMID- 9622245
TI  - Distribution of heterotrimeric G-protein beta and gamma subunits in the rat
      brain.
AB  - Heterotrimeric G-proteins, comprising alpha, beta and gamma subunits, have been
      shown to play a central role in coupling multiple receptors to a variety of
      enzymes and ion channels. In vitro studies have demonstrated the existence of
      selective interactions between various alpha, beta and gamma subunits, as well as
      between specific heterotrimers and target receptor and effector proteins.
      However, little is known of the physiological relevance of such associations, and
      the determinants of specificity in G-protein signaling within the brain remain
      largely unidentified. To investigate the possibility that specific heterotrimeric
      interactions result from discrete localizations of the G-protein subunits within
      the brain, we have used the technique of in situ hybridization to map the
      distribution of G-protein beta and gamma subunits in the rat brain. Beta1, beta2,
      beta3 and beta5 subunits were found to be widely expressed throughout the rat
      brain, whilst beta4 and the G-protein gamma subunit messenger RNAs generally
      showed more discrete expression patterns. The expression patterns for these
      subunits suggest that individual beta and gamma subunits may be co-expressed in
      certain cell types and brain regions; a particularly intriguing and striking co
      localization was observed in the case of beta4 and gamma2 subunit messenger RNAs
      in layer VI of the occipital cortex. The localizations of the G-protein beta and
      gamma subunits, and their potential coupling to various receptor/effector
      systems, are discussed.

PMID- 9622246
TI  - Regulation of heterologously expressed transient receptor potential-like channels
      by calcium ions.
AB  - The Drosophila melanogaster gene product TRPL (transient receptor potential-like)
      is a Ca2+-permeable cation channel that contributes to the light-induced Ca2+
      entry in Drosophila photoreceptors and bears homology to several recently cloned
      mammalian channels. Intracellular Ca2+ has been implicated to stimulate TRPL
      channels. This constitutes a potentially dangerous mechanism that may lead to
      Ca2+ overload. Therefore, we studied whether TRPL channels, like other Ca2+
      permeable channels, are inhibited by intracellular Ca2+ concentrations in the
      micromolar range and whether this effect is mediated by calmodulin. In Sf9 cells
      expressing the TRPL gene along with histamine H1 receptors after infection with
      baculoviruses containing the corresponding complementary DNA, histamine-induced
      TRPL currents were inhibited by intracellular Ca2+ with an IC50 of 2.3 microM.
      Moreover, TRPL currents were reversibly attenuated by a preceding
      hyperpolarization. This attenuation reflected the action of an increased Ca2+
      influx, since it was abolished in the absence of extracellular Ca2+ and enhanced
      by raising extracellular Ca2+ to 20 mM. Finally, the activity of TRPL channels in
      inside-out patches was reversibly inhibited by raising the Ca2+ concentration on
      the cytosolic side of the patches to 10-50 microM. Addition of calmodulin or the
      calmodulin inhibitor calmidazolium did not modify the inhibition of the TRPL by
      Ca2+. We conclude that high intracellular Ca2+ concentrations inhibit the TRPL,
      but no evidence was found for the requirement of calmodulin. This mechanism makes
      Ca2+ influx through the TRPL self-limiting. Furthermore, the TRPL may allow one
      to study the structural requirements for channel regulation by Ca2+.

PMID- 9622247
TI  - Voltage-operated potassium currents in the somatic membrane of rat dorsal root
      ganglion neurons: ontogenetic aspects.
AB  - Whole-cell transmembrane potassium currents were studied in somatic membrane of
      freshly isolated rat dorsal root ganglion neurons. We defined three types of
      potassium currents, which were separated on the basis of their different
      potential dependence of activation and sensitivity to external tetraethylammonium
      and 4-aminopyridine. The potential dependence of kinetic and steady-state
      properties of a fast inactivating potassium current, a slow inactivating
      potassium current and a non-inactivating delayed rectifier current were described
      by the Hodgkin-Huxley equations. A transient fast inactivating potassium current
      was activated at the most negative membrane potentials and was not reduced in the
      presence of 10 mM tetraethylammonium in the external solution. 4-Aminopyridine (2
      mM) caused an 80% inhibition of this current. The activation of the fast
      inactivating potassium current was properly described by fitting a single
      exponent raised to the fourth power. The time constant of activation changed from
      4 to 1 ms in the voltage range between -30 and +40 mV. The time constant of
      inactivation decreased from 35 to 15 ms over the same range of potentials.
      Parameters for the fit of a Boltzmann equation to mean values for steady-state
      activation were V1/2=-20mV, k=11.8mV, and for steady-state inactivation V1/2= -85
      mV, k=-9.8 mV. A transient slow inactivating potassium current had an activation
      threshold between -40 and -30 mV. At 2 mM 4-aminopyridine, the depression of the
      slow potassium current was 55%. The extracellular application of 10 mM
      tetraethylammonium was less effective and evoked a 40% reduction. The activation
      of the slow inactivating potassium current was also described by a single
      exponential function raised to the fourth power. The time constant of activation
      decreased from 12 ms at a membrane potential of -10 mV to 4 ms at the potential
      of 60 mV. The inactivation of slow inactivating potassium current was described
      by two exponents. The time constant for the fast exponent ranged from 300 ms at 
      20 mV to 160 ms at +60 mV. The slower exponent was also potential dependent and
      its time constant ranged from approximately 2600 to 1600 ms over the same
      potentials. Parameters for the Boltzmann equation fittings to mean values were
      V1/2= -12.8 mV, k=13.4 mV and V1/2= -54.6 mV, k= -12 mV for steady-state
      activation and inactivation, respectively. A non-inactivating delayed rectifier
      potassium current was activated at the most positive membrane potentials. This
      non-inactivating current did not change in the presence of 4-aminopyridine.
      Extracellular tetraethylammonium (10 mM) caused a 70% reduction of this current.
      The activation of the non-inactivating potassium current was described by one
      exponent raised to the fourth power. The time constant for activation ranged from
      85 ms at -5 mV to 30 ms at 45 mV. No time-dependent inactivation was observed
      during 15-s testing potentials in the voltage range between 10 and +60 mV. The
      activation behavior was characterized by V1/2=15.3 mV, k=12.5 mV. The densities
      of these potassium currents were studied for three groups of animals: one, five
      to six and 14-15 days of postnatal development. Fifty cells were examined in each
      age group. All three types of potassium currents were found in each investigated
      neuron. The mean densities of slow and fast inactivating potassium currents
      increased during ontogenetic development. The densities of non-inactivating
      delayed rectifier potassium current decreased in the first week of ontogenetic
      development and did not change thereafter.

PMID- 9622248
TI  - Angiotensin II-induced calcium signalling in neurons and astrocytes of rat
      circumventricular organs.
AB  - The subfornical organ and organum vasculosum laminae terminalis represent
      neuroglial circumventricular organ structures bordering the anterior third
      cerebral ventricle. Owing to the absence of the blood-brain barrier, the cellular
      elements of the subfornical organ and the organum vasculosum laminae terminalis
      can be reached by circulating messenger molecules transferring afferent
      information. As demonstrated for the control of extracellular fluid composition,
      the circulating hormone angiotensin II acts on these sensory circumventricular
      organs to induce drinking, elevated peripheral resistance and neurohypophyseal
      hormone release via interaction with membrane-spanning receptor proteins. To
      characterize the cell-specific distribution of angiotensin II receptors within
      the circumventricular organs, primary cell cultures derived from the subfornical
      organ or organum vasculosum laminae terminalis of five- to six-day-old rat pups
      were used to measure alterations in intracellular calcium at the single cell
      level. Neurons and astrocytes were identified by immunocytochemical staining for
      specific marker proteins. Bath application of angiotensin II (10(-10)-10(-6) M)
      dose-dependently induced calcium transients in neurons (19.6%) and astrocytes
      (15.7%), and angiotensin II threshold concentrations to elicit intracellular
      calcium signalling proved to be one order of magnitude higher in astrocytes as
      compared to neurons (10(-9) M). At angiotensin II concentrations higher than 10(
      7) M, pronounced desensitization of the angiotensin II receptor occurred.
      Employing the angiotensin II receptor antagonists losartan (DUP-753; AT1
      receptor) and PD-123319 (AT2-receptor), exclusive expression of the AT1 receptor
      subtype coupled to intracellular calcium concentration signalling could be
      demonstrated for neurons and astrocytes. In all cells examined, the angiotensin
      II-evoked increase in intracellular calcium concentrations could be fully
      suppressed in the absence of extracellular calcium. Co-activation by angiotensin
      II and other agents (vasopressin, its fragment 8-arginine-vasopressin(4-9),
      oxytocin, endothelin) was indicated for subfornical organ neurons and organum
      vasculosum laminae terminalis astrocytes.

PMID- 9622249
TI  - Stimulation of P2Y-purinoceptors on astrocytes results in immediate early gene
      expression and potentiation of neuropeptide action.
AB  - The action of adenosine-5'-O-(2-thiodiphosphate), a non-hydrolysable purine
      analogue and potent P2Y1-purinoceptor agonist, was studied on immediate early
      gene expression in rat astrocyte cultures. A rapid and transient increase in c
      fos, junB, c-jun and Tis11 messenger RNA was observed in cultured astrocytes
      after treatment with adenosine-5'-O-(2-thiodiphosphate). Maximal induction of
      immediate early gene expression was obtained within 30 min of stimulation and c
      fos was the most sensitive indicator of P2Y-purinoceptor activation. Calcitonin
      gene-related peptide has also been shown to be a potent inducer of c-fos
      messenger RNA in cultured astroglial cells. The combined stimulation of
      astrocytes with calcitonin gene-related peptide and adenosine-5'-O-(2
      thiodiphosphate) resulted in the potentiated expression of c-fos messenger RNA.
      The superinduction of immediate early gene expression by calcitonin gene-related
      peptide and extracellular ATP in cultured astrocytes might result from
      intracellular signal transduction cross-talk, since adenosine-5'-O-(2
      thiodiphosphate) was found to increase calcitonin gene-related peptide-induced
      cyclic AMP accumulation by 35%. Phorbol 12-myristate 13-acetate also increased
      calcitonin gene-related peptide-evoked cyclic AMP accumulation and led to the
      induction of immediate early gene expression, suggesting that protein kinase C
      might be at least in part involved in purinergic cross-talk. Our results
      demonstrate synergistic roles for extracellular ATP and calcitonin gene-related
      peptide in the transcriptional activation of astroglial cells.

PMID- 9622250
TI  - Carnosine-like immunoreactivity in astrocytes of the glial tubes and in newly
      generated cells within the tangential part of the rostral migratory stream of
      rodents.
AB  - In the nervous system, the aminoacylhistidine dipeptide carnosine (beta-alanyl-L
      histidine) has been shown to be expressed in the olfactory receptor neurons and
      in brain astrocytes. Using immunocytochemical techniques, we report here a dense
      carnosine-like immunoreactivity in the subependymal layer of the rodent
      forebrain. Since the subependymal layer involves two distinct compartments
      (astrocytic cells forming glial tubes and newly-generated cells of the rostral
      migratory stream, here organized to form chains contained within the glial tubes
      [Brannon Thomas L. et al. (1996) Glia 17, 1-14; Jancovski A. and Sotelo C. (1996)
      J. comp. Neurol. 258, 112-124; Lois C. et al (1996) Science 271, 978-981; Peretto
      P. et al. (1997) Brain Res. Bull. 42, 9-21]), we investigated in detail the
      cellular distribution of carnosine-like immunoreactivity in this area. By using
      double labelling techniques with antisera raised against carnosine and specific
      markers of glial tubes or chains of migrating cells, we show that carnosine-like
      immunoreactivity is associated with both the compartments. On the other hand,
      unlike markers of the rostral migratory stream, carnosine-like immunoreactivity
      was not observed in isolated, migrating cells located outside the subependymal
      layer, which spread through the olfactory bulb in a radially-oriented manner.
      This suggests that carnosine is transiently expressed by cells of the rostral
      migratory stream when moving in the tangentially-oriented part of the migration
      route. Moreover, we investigated the distribution of carnosine-like
      immunoreactivity in the postnatal rat forebrain and found that it is detectable
      in the subependymal layer only starting from the third postnatal week, although
      it is well known that the dipeptide is present in the olfactory receptor neurons
      since the embryonic day 16 [Biffo S. et al. (1992) J. chem Neuroanat. 5, 5162].
      Taken together, these results show that camosine, other than abundantly present
      in astrocytes of the glial tubes, is associated to the tangential part of the
      rostral migratory stream.

PMID- 9622251
TI  - Testosterone has potent, selective effects on the morphology of pelvic autonomic
      neurons which control the bladder, lower bowel and internal reproductive organs
      of the male rat.
AB  - Although gonadal steroids are important determinants of the development and
      activity of various neuronal circuits in the brain and spinal cord, their
      function has been relatively poorly studied in the peripheral nervous system. In
      the present work, the effects of pre- and postpubertal castration were examined
      on the morphology of autonomic neurons that supply pelvic visceral organs in male
      rats. These neurons were identified by peripheral injection of fluorescent
      retrograde tracers and, in the major pelvic ganglion, were further classified as
      sympathetic or parasympathetic by means of immunostaining for tyrosine
      hydroxylase. Sizes of ganglion cell somata were indicated by areas of nucleated
      profiles in cryosections. The results show that, irrespective of whether
      castration was carried out at two or seven weeks-of-age, noradrenergic pelvic
      neurons that supply the vas deferens, prostate gland, urinary bladder or colon
      achieved only approximately 60% of the size of those in unoperated controls. In
      contrast, cholinergic pelvic neurons were unaffected by castration unless they
      supplied reproductive targets. Pre- and paravertebral sympathetic neurons that
      supplied the pelvic viscera were only slightly smaller following castration or
      were unchanged, depending on their target. All effects of castration were
      prevented by testosterone replacement following surgery. Androgen receptor
      immunoreactivity was particularly prevalent in the nuclei of some pelvic ganglion
      neurons. The studies suggest that circulating androgens are essential for the
      maturation and maintenance of the structure of select groups of autonomic neurons
      that supply the viscera. The presence of androgen receptor immunoreactivity in
      many of these neurons indicates that direct neuronal effects of androgens are
      possible. However this does not exclude other less direct mechanisms of steroid
      action on neurons, such as by an effect on target organs, neurotrophic factor
      release or peripheral vascular supply. These studies point to the androgenic
      steroids as potentially important determinants of autonomic reflex function.

PMID- 9622252
TI  - The octadecaneuropeptide-induced response of corticotropin-releasing hormone
      messenger RNA levels is mediated by GABA(A) receptors and modulated by endogenous
      steroids.
AB  - The involvement of endogenous benzodiazepine octadecaneuropeptide in the
      regulation of corticotropin-releasing hormone messenger RNA expression has been
      studied using in situ hybridization technique. Intracerebroventricular injection
      of octadecaneuropeptide (4 microg/kg) induced a 26% decrease in the corticotropin
      releasing hormone messenger RNA expression in the hypothalamic paraventricular
      nucleus. Concomitant injection of octadecaneuropeptide and i.p. injection of the
      GABA(A) receptor agonist muscimol (4 mg/kg) potentiated the corticotropin
      releasing hormone messenger RNA decrease ( - 34%). The depressing effect of
      octadecaneuropeptide on corticotropin-releasing hormone gene expression was
      totally reversed by pretreatment of the animals with the GABA(A) receptor
      antagonist picrotoxin (5 mg/kg; i.p.) or by pretreatment with the benzodiazepine
      receptor antagonist flumazenil (4 mg/kg; i.p.). To determine the reciprocal
      involvement of adrenal and sexual steroids in this regulation, animals are
      adrenalectomized and/or castrated. Adrenalectomy reversed the effect induced by
      octadecaneuropeptide, which increased corticotropin-releasing hormone messenger
      RNA expression (+21%), while castration did not modify the negative influence of
      octadecaneuropeptide. When rats were adrenalectomized and castrated, the
      adrenalectomy influence was predominant, since octadecaneuropeptide increased
      significantly the hybridization signal (+18%). The involvement of neurosteroids,
      especially reduced metabolites of progesterone was also investigated. The
      concomitant injection of octadecaneuropeptide and subcutaneous injection of the
      5alpha-reductase inhibitor MK-906 (14 mg/kg) to adrenalectomized and castrated
      rats, reduced significantly by 60% the increase of corticotropin-releasing
      hormone messenger RNA expression induced by octadecaneuropeptide. These results
      indicate that in vivo the endogenous benzodiazepine octadecaneuropeptide, via an
      activation of the benzodiazepine sites of the GABA(A) receptor, negatively
      modulates corticotropin-releasing hormone neuronal activity and that this
      modulation can be negatively or positively influenced by central and peripheral
      steroids.

PMID- 9622253
TI  - Age-induced decrease of glycoprotein Po and myelin basic protein gene expression
      in the rat sciatic nerve. Repair by steroid derivatives.
AB  - The data here reported show that the gene expression of the glycoprotein Po and
      of the myelin basic protein, the major components of myelin in the peripheral
      nervous system, dramatically decreases with ageing in the sciatic nerve of normal
      male rats. A one-month treatment with dihydroprogesterone, the 5alpha-reduced
      derivative of progesterone, is able to partially restore the fall in Po gene
      expression occurring in the sciatic nerve of aged male rats, without
      significantly modifying the gene expression of the myelin basic protein. In
      cultures of neonatal Schwann cells (the peripheral nervous system elements
      involved in the synthesis of myelin), the addition of progesterone and of
      dihydroprogesterone significantly increases Po gene expression; the 3alpha
      reduced metabolite of dihydroprogesterone, tetrahydroprogesterone proved to be
      even more effective. These data suggest that the effect of progesterone is linked
      to its conversion into dihydroprogesterone and especially into
      tetrahydroprogesterone, since Schwann cells possess the 5alpha-reductase-3alpha
      hydroxysteroid dehydrogenase system. The data provide the first demonstration
      that ageing decreases the gene expression of two major components of the
      peripheral myelin in the sciatic nerve; they also show that this phenomenon may
      be partially reversed by progesterone derivatives, which might act by stimulating
      Po gene expression in the Schwann cells.

PMID- 9622254
TI  - Faster recovery in central than in peripheral auditory system following a
      reversible cochlear deafferentation.
AB  - Included among the exciting findings in auditory neuroscience are (i) central
      plasticity after peripheral injury and (ii) regeneration of auditory nerve fibres
      following excitotoxic damage. The present study extends our understanding of
      auditory system plasticity by examining changes in peripheral and central
      physiology as the cochlea recovers from temporary deafferentation due to
      excitotoxicity. Application of kainic acid (60 mM) to the round window membrane
      substantially depressed responses from both auditory nerve and brain stem
      (inferior colliculus), without affecting distortion-product otoacoustic emissions
      from the inner ear. The auditory nerve input/output functions recovered over a 30
      day period whereas recovery of brainstem response amplitudes occurred within five
      days. In contrast to amplitudes, thresholds at both peripheral and central levels
      recovered simultaneously, within five days after kainic acid application. The
      results indicate that (i) cochlear afferent neurons can recover after excitotoxic
      damage; (ii) response threshold itself, either central or peripheral, is not
      sufficient to assess the integrity of the auditory periphery; (iii) the central
      auditory system can recover more rapidly than the periphery; and (iv) the system
      can maintain its function in the normal range as peripheral function continues to
      improve.

PMID- 9622255
TI  - Degenerative phenomena and reactive modifications of the adult rat inferior
      olivary neurons following axotomy and disconnection from their targets.
AB  - Adult olivocerebellar axons are capable of vigorous regeneration when provided
      with growth-permissive environmental conditions. To elucidate the contribution of
      intrinsic properties to the regenerative capabilities of inferior olivary
      neurons, we have examined the cellular modifications occurring in these neurons
      following axotomy and target deprivation in the absence of exogenous growth
      promoting influences. Axotomized inferior olivary neurons undergo perikaryal
      shrinkage, dendritic atrophy and a loss of anti-calbindin immunoreactivity. A
      conspicuous cell death occurs during the first few weeks after lesion, but about
      35% of the affected neurons survive up to 60 days. Coincidentally, a subset of
      the injured nerve cells become strongly reactive for NADPH diaphorase
      histochemistry, and this expression is correlated with survival in the medial
      accessory olive and in the principal olive. In addition, the affected neurons
      express or maintain the expression of several markers related to regenerative
      processes, including transcription factors c-Jun, JunD and Krox-24, the growth
      associated protein GAP-43 and the developmentally regulated calcitonin gene
      related peptide (CGRP). The expression of all these markers is sustained up to
      two months after lesion, the longest survival time examined. These results show
      that although adult axotomized inferior olivary neurons undergo severe regressive
      modifications leading to a conspicuous cell loss, at least a subset of them is
      resistant to the lesion. In addition, the long-lasting expression of several axon
      growth associated markers expressed in these neurons in response to injury
      reveals that they are endowed with a strong intrinsic regenerative potential.

PMID- 9622256
TI  - Topographical organization of inferior olive cells projecting to translation and
      rotation zones in the vestibulocerebellum of pigeons.
AB  - Previous electrophysiological studies in pigeons have shown that the
      vestibulocerebellum can be divided into two parasagittal zones based on responses
      to optic flow stimuli. The medial zone responds best to optic flow resulting from
      self-translation, whereas the lateral zone responds best to optic flow resulting
      from self-rotation. This information arrives from the retina via a projection
      from the accessory optic system to the medial column of the inferior olive. In
      this study we investigated inferior olive projections to translational and
      rotational zones of the vestibulocerebellum using the retrograde tracer cholera
      toxin subunit B. Extracellular recordings of Purkinje cell activity (complex
      spikes) in response to large-field visual stimuli were used to identify the
      injection sites. We found a distinct segregation of inferior olive cells
      projecting to translational and rotational zones of the vestibulocerebellum.
      Translation zone injections resulted in retrogradely labeled cells in the
      ventrolateral area of the medial column, whereas rotation zone injections
      resulted in retrogradely labeled cells in the dorsomedial region of the medial
      column. Motion of any object through space, including self-motion of organisms,
      can be described with reference to translation and rotation in three-dimensional
      space. Our results show that, in pigeons, the brainstem visual systems
      responsible for detecting optic flow are segregated into channels responsible for
      the analysis of translational and rotational optic flow in the inferior olive,
      which is only two synapses from the retina.

PMID- 9622257
TI  - Survival and functional demonstration of interregional pathways in fore/midbrain
      slice explant cultures.
AB  - An important general question in neurobiology concerns the development and
      expression of the rich context of neuronal phenotypes, especially in relation to
      the diverse patterns of connectivity. Organotypic cultures of brain slices may
      offer distinct advantages for such studies if such a preparation survives,
      maintains a wide diversity of neuronal phenotypes and displays appropriate
      synaptic connections between regions. To address these requirements, we utilized
      long-term organotypic cultures of intact horizontal slices of rat forebrain and
      midbrain and assessed a variety of markers of phenotype in combination with
      functional tests of connectivity. This explant preparation displayed a distinct
      viability requirement such that the greatest explant survival was seen in slices
      taken from pups of less than postnatal day 7 and was independent of N-methyl-D
      aspartate channel blockade. The anatomical features of the major brain regions
      (e.g., neocortex, striatum, septum, hippocampus, diencephalon and midbrain) were
      observed in their normal boundaries. The presence of cholinergic and
      catecholaminergic neurons was demonstrated with acetylcholinesterase
      histochemistry and tyrosine hydroxylase immunohistochemistry. Labelled neurons
      displayed multiple, regionally-appropriate cytoarchitectures and, in some cases,
      could be seen to project to brain regions in a manner quite similar to that seen
      in vivo. Finally, the direct demonstration of spontaneous and evoked
      interregional excitatory synaptic transmission was made using whole-cell patch
      clamp recordings from striatal neurons which revealed an intact glutamate-using
      corticostriatal pathway. This simple explant preparation appears to contain a
      rich diversity of neuronal types and synaptic organization. Therefore, this
      preparation appears to have several distinct advantages for basic neurobiologic
      research since it combines long-term culture viability and many features of
      mature brain including complex interregional neuronal systems.

PMID- 9622258
TI  - Developmental study of Muller cells in the rat retina using a new monoclonal
      antibody, RT10F7.
AB  - We produced the monoclonal antibody RT10F7, characterized its antigenic
      specificity and expression in the adult and developing retina, in cultured
      retinal cells and in other parts of the central nervous system. In metabolically
      labelled retinal cultures RT10F7 immunoprecipitated a protein of approximately
      36,000 mol. wt. In the adult, RT10F7 stained endfeet of Muller cells in the
      ganglion cell layer, four horizontal bands in the inner plexiform layer, and
      radial fibres in the outer plexiform layer which terminated at the outer limiting
      membrane. In the inner nuclear layer, most somata were underlined by Muller
      processes that wrapped around them, but some cell bodies were immunoreactive for
      RT10F7 in the cytoplasm. During development, postnatal day 21 was the first age
      at which the adult pattern of immunoreactivity was present, although a fourth
      band in the inner plexiform layer was less clear than for the adult. By 14 and
      eight days after birth, the pattern of RT10F7 immunoreactivity approximated that
      of the adult; however, only three bands and one band were present, respectively,
      in the inner plexiform layer. At earlier ages, postnatal days 4, 1 and embryonic
      ages 19 and 15, the monoclonal antibody stained Muller cell endfeet and radial
      fibres, from the inner plexiform layer through the neuroblastic layer to the
      outer limiting membrane. At these ages, the immunoreactivity was more prominent
      at the level of Muller cell endfeet. The monoclonal antibody stained glia in
      preparations of dissociated retinal cells maintained in culture but not
      astrocytes or oligodendrocytes from optic nerve cultures. In brain sections,
      tanycytes exhibited RT10F7 immunoreactivity. The monoclonal antibody RT10F7
      recognized a specific cell type in the retina, the Muller cell. In the adult and
      developing retina, RT10F7 recognized an antigen that is present primarily in
      Muller cell processes. This feature allowed us to follow the maturation of the
      Muller cell and correlate it with developmental events in the retina. RT10F7 is a
      specific marker for Muller cells in vivo and in vitro and may be useful for
      studies of function of Muller cells after ablation or after injuries that are
      known to activate Muller cells.

PMID- 9622259
TI  - Putative neuropeptides and an EF-hand motif region are encoded by a novel gene
      expressed in the four giant interneurons of the terrestrial snail.
AB  - Nine giant interneurons located in the pleural and parietal ganglia of the
      terrestrial snail Helix lucorum L. were reported to be a key element in the
      network controlling withdrawal behaviour of the animal. Using a combination of
      complementary DNA subtraction cloning and differential screening approaches we
      have isolated a novel gene named HCS2 which is expressed predominantly in a
      subset of these interneurons. The predicted amino acid sequence of the HCS2
      protein contains at the N-terminus a hydrophobic leader sequence and four
      putative neuropeptides, and at the C-terminus a perfect match to the consensus
      motif of the EF-hand family of the Ca2+-binding proteins. All four predicted
      neuropeptides bear a C-terminal signature sequence Tyr-Pro-Arg-X (where X is Ile,
      Leu, Val or Pro), and three of them are likely to be amidated. Physiological
      action of three synthetic peptides corresponding to the predicted mature HCS2
      peptides mimics fairly well the described action of parietal interneurons on
      follower motoneurons controlling pneumostome closure. In situ hybridization
      experiments demonstrated that the HCS2 gene is selectively expressed in the four
      parietal giant interneurons, as well as in several small unidentified neurons.
      The onset of the HCS2 transcription during embryogenesis coincides temporally
      with the time-point when the first withdrawal responses of the embryo to tactile
      stimulation appear. We propose that the HCS2 gene encodes a hybrid precursor
      protein whose processed products act as neuromodulators or neurotransmitters
      mediating the withdrawal reactions of the snail, and in addition may participate
      in the calcium regulatory pathways or calcium homeostasis in command neurons.

PMID- 9622260
TI  - TUNEL-positive cells in the substantia nigra of C57BL/6 mice after a single bolus
      of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

PMID- 9622261
TI  - Validation of a fall-risk screening test, the Elderly Fall Screening Test (EFST),
      for community-dwelling elderly.
AB  - Falls are the most common type of injury among the elderly, and the source of
      both functional and psychological morbidity. The aim of this study was to
      validate the Elderly Fall Screening Test (EFST). In a community primary-care
      clinic, the members 60 years or older who were functionally independent were
      screened. Of the 568 elderly persons who met these criteria, 361 were interviewed
      once and 283 persons were re-interviewed a year later. The EFST, a five-item
      test, was used to divide participants into low- and high-risk groups. Concurrent
      criterion validity was assessed by physical examinations conducted by physicians
      who were blind as to the risk designation. Using data from the follow-up
      interview, predictive validity was assessed on both fall-related and general
      health measures. Based on the results of the EFST, 28% of the respondents were
      designated as being at high risk for falls (i.e. having a score of two or more
      risk items). The results of physicians' examinations corroborated the screening
      test results in 75% of the cases, with 83% sensitivity and 69% specificity. In
      the follow-up interview, the high-risk group, as compared to the low-risk group,
      was more likely to have high scores on EFST, a fall in the past month or year,
      frequent near falls, and an injurious fall. Those with high EFST scores were more
      likely to report four or more sick days in the past six months, a hospitalization
      in the past year, poor self-rated health, a decline in health in the past 6
      months, and symptoms of depression. The EFST has both criterion and predictive
      validity. It can be useful in community-based prevention programmes with
      functionally independent elderly people.

PMID- 9622262
TI  - The mobility needs of women with physical disabilities in India: a functional
      perspective.
AB  - The purpose of this research was to explore the functional mobility needs of
      women with lower extremity disabilities in Gujarat state, India. Ten women
      participated in a Mobility Needs Assessment which used multiple data collection
      methods to gather quantitative and qualitative information in five main areas.
      The results indicated that the physical environment was diverse, at times
      unpredictable, and environmental barriers were commonly encountered. The women
      travelled relatively long distances to perform self-care activities such as
      bathing and toileting. Furthermore, the women had compensated for their
      disability by implementing different strategies, such as four methods of
      locomotion, ten sitting positions, and various methods for carrying objects.
      Activities of daily living were similar amongst the women, although some women
      required assistance to complete specific activities successfully. Although the
      women expressed different views on how they felt about their present level of
      mobility, all were able to identify activities they wished to perform if they
      could move more easily. The resulting information contributed towards an area
      where little has been documented previously.

PMID- 9622263
TI  - Eligibility criteria for NHS long stay care: the relationship between clinical
      need, dependency, and staff perception.
AB  - A study was undertaken by a Scottish Health Authority to determine future
      provision of NHS long stay in-patient beds for young physically disabled people
      (aged < 65), and eligibility criteria for admission to such care. As part of the
      development of care in the community, only patients requiring specialist medical
      and nursing care should continue to be placed in NHS care. Resources freed from
      the resulting closure of NHS beds will be transferred to Social Services to
      develop alternative packages of care in the community, based on need rather than
      precedent. Achieving the balance, in terms of the correct level of continuance of
      NHS long stay care and redeployment of resources, requires careful planning. This
      study, involving all young physically disabled patients in NHS care in Argyll and
      Clyde Health Board, combined the assessment of dependency using validated scales
      (CAPE, FIM, and ERSS), with staff perception of dependency and with clinical
      criteria developed for a series of balance of care studies in this authority.
      These clinical criteria indicate the need for specialist medical and nursing
      care. By examining the relationship between dependency and staff perception, it
      has been possible to plan long stay provision on a population basis. The criteria
      for admission have been adopted for local clinical use and form the basis for
      appeals procedures for patients deemed appropriate for discharge.

PMID- 9622264
TI  - The use of non-specialist personnel in providing a service for children disabled
      by hearing impairment.
AB  - PURPOSE: This paper addresses the issue of how to provide health services for
      hearing-impaired children in the developed world. Most children live in
      developing countries, with no access to audiological or therapy services. METHOD:
      The paper reviews the prevalence of hearing impairment in developing countries
      and stresses the need to examine the details not only of the hearing impairment
      but also of the disabling consequences of hearing loss, especially in the
      developing world where the provision of hearing aids (or other amplification) is
      a financial and/or logistical impossibility for most children. RESULTS:
      Institutional services in developing countries achieve very low coverage rates.
      CONCLUSIONS: Community-based rehabilitation (CBR) reaches disabled children more
      effectively, and the final part of the paper suggests ways in which CBR workers
      can assist hearing-impaired children.

PMID- 9622265
TI  - Is the Barthel Scale appropriate in non-industrialized countries? A view of rural
      Pakistan.
AB  - PURPOSE: To determine if the Barthel Index, a conventional scale for assessing
      disability, is appropriate for stroke patients in rural Pakistan, rather than an
      observational study by visiting stroke patients in their homes. METHOD: Stroke
      patients attending hospital out patient clinics in Islamabad, together with
      others identified in local villages, were assessed to test the validity of the
      Barthel Activities of Daily Living Scale. RESULT: For each item on the disability
      scale, differences in local customs, lifestyle and architecture meant that the
      Barthel Scale was not appropriate in rural Pakistan. CONCLUSIONS: There is
      unlikely to be a disability scale which can be applicable universally. Care must
      be taken when standard scales are used for international comparisons of stroke
      disability.

PMID- 9622266
TI  - Distribution of endothelin-1 (ET) receptors (ET(A) and ET(B)) and immunoreactive
      ET-1 in porcine saphenous vein-carotid artery interposition grafts.
AB  - Proliferation of vascular smooth muscle cells (VSMC) is a principal event in
      neointima formation in saphenous vein-coronary artery bypass grafts. Since
      endothelin-1 (ET-1) promotes VSMC replication and ET-1 receptor antagonists
      inhibit neointima formation in arterial injury models, it is reasonable to
      propose that ET-1 may be involved in neointima formation in vein grafts. However,
      it is not known what alterations of ET-1 and its receptors (if any) occur in vein
      grafts. The objective of this study, therefore, was to investigate the
      distribution of ET-1 and ET-1 receptor subtypes (ET(A) and ET(B)) in porcine vein
      grafts. Unilateral interposition saphenous vein grafting was performed by end to
      end anastomosis after excision of a segment of carotid artery in Landrace pigs.
      One month after surgery, vein grafts, ungrafted saphenous veins and carotid
      arteries were excised, ET-1 immunoreactivity identified by immunocytochemistry
      and ET(A) and ET(B) receptor subtypes studied using autoradiography. In vein
      grafts, there was a greater density of ET(A) compared to ET(B) receptors in both
      the tunica media and neointima. ET(A) binding in the tunica media of ungrafted
      saphenous vein was greater than that in the carotid artery or vein grafts, but
      greater in the vein graft compared to the carotid artery. Immunoreactive ET-1 was
      located in endothelial cells and throughout the neointima of the vein graft.
      Dense ET-1 binding (to both ET(A) and ET(B) receptors) was also associated with
      microvessels in the adventitia within the graft. In vein grafts, there was strong
      ET(B) binding to neutrophils which were present in high numbers at the
      subendothelium and within the adventitia. It is concluded ET(A) receptors may
      play a role in vein graft thickening at the medial and neointimal VSMC level,
      whereas ET(B) receptors may play a role in microangiogenesis. The higher levels
      of ET(A) receptors in the tunica media of ungrafted saphenous vein relative to
      the carotid artery and vein graft may also render this conduit susceptible to
      neointima formation. These data indicate that studies on the effect of ET
      receptor antagonists on the pathobiology of vein graft disease is warranted.

PMID- 9622267
TI  - A controlled trial of the effects of pattern of alcohol intake on serum lipid
      levels in regular drinkers.
AB  - To determine whether the effects of drinking pattern (predominantly weekend
      versus daily drinking) have differential effects on serum lipids, 55 healthy male
      drinkers were recruited on the basis of a regular alcohol intake, 210-500 ml
      absolute alcohol/week (approximately 3-6 standard drinks/day), with more than 60%
      consumed as beer. Fourteen subjects were categorised as predominantly weekend
      drinkers, while 41 subjects regularly drank on a daily basis. After maintenance
      of their drinking pattern during a 4-week familiarisation, subjects were
      randomised to either consume low alcohol beer (0.9%, v/v) only, or to maintain
      their usual drinking habit consuming full-strength beer (5%, v/v) for the next 4
      weeks. They then switched to full-strength or low alcohol beer, respectively, for
      a further 4 weeks. Their drinking pattern remained constant during the study. In
      both weekend and daily drinkers, a reduction in alcohol intake (i.e. from 387
      ml/week to 88 ml/week for weekend drinkers and from 418 ml/week to 95 ml/week for
      daily drinkers, respectively, P < 0.001) resulted in a similar 0.12 mmol/l fall
      in HDL-C (P < 0.01) with a concomitant significant fall in both apolipoproteins A
      I and A-II. In daily drinkers total cholesterol fell by 0.28 mmol/l (P < 0.001)
      and triglyceride by 0.22 mmol/l (P < 0.01) with a reduction in alcohol intake,
      but no change in LDL-C was seen. In contrast, weekend drinkers total cholesterol
      was unchanged while triglyceride decreased by 0.26 mmol/l (P < 0.05) and LDL-C
      increased by 0.25 mmol/l (P < 0.01). Lp(a) increased with a reduction in alcohol
      intake in both daily (9.1 U/l, P < 0.05) and weekend drinkers (27.6 U/l, P =
      0.07). Previous reports of a more atherogenic lipid profile with episodic versus
      regular daily drinking were not confirmed in this study and potentially
      favourable effects of alcohol to increase HDL-C and decrease Lp(a) were shown to
      be independent of drinking pattern in these moderate to heavy drinkers.

PMID- 9622268
TI  - Cardiovascular risk factors in relation to cigarette smoking: a population-based
      survey among Asians in Singapore.
AB  - To investigate how cigarette smoking increases the risk of cardiovascular
      disease, risk factors were compared between 166 cigarette smokers and 312 non
      smokers, in a random sample of males (Chinese, Malays and Asian Indians) aged 30
      69 years from the general population of Singapore. There was adjusted for age and
      ethnic group. The prevalence of hypertension was lower in cigarette smokers
      (15.2%) than non-smokers (21.9%), with the difference reduced by adjustment for
      body mass index (BMI). Smokers had: lower mean serum HDL-cholesterol (0.76 versus
      0.81 mmol/l) and higher mean serum fasting triglyceride (1.92 versus 1.71
      mmol/l), which will increase atherosclerosis; higher mean plasma fibrinogen (2.75
      versus 2.67 g/l) and plasminogen activator inhibitor 1 [PAI-1] (24.9 versus 22.2
      ng/ml), which will increase thrombosis; and lower mean plasma vitamin C (4.4
      versus 6.4 mg/l) and serum selenium (118 versus 123 microg/l), which may increase
      atherosclerosis. Adjustment for BMI slightly increased the differences for HDL
      cholesterol, fasting triglyceride, fibrinogen and PAI-1, indicating that less
      generalised obesity among smokers reduces their increased cardiovascular disease
      risk. Smoking was not found to be related to: diabetes mellitus; serum total
      cholesterol, LDL-cholesterol, apolipoproteins A1 and B and lipoprotein(a); plasma
      factor VIIc and prothrombin fragment 1 + 2; and plasma vitamins A and E and serum
      ferritin. There was no evidence of increased insulin resistance in smokers, as
      measured by mean fasting serum insulin.

PMID- 9622269
TI  - Effects of chronic social separation on cardiovascular disease risk factors in
      female cynomolgus monkeys.
AB  - A lack of social support is associated with increased risk of coronary heart
      disease morbidity and mortality in human beings. Similarly, chronic social
      separation (single cage housing) potentiates atherosclerosis in female monkeys.
      Under the hypothesis that autonomic arousal and/or ovarian impairment may mediate
      this effect (as both are associated with increased atherosclerosis), heart rate
      and luteal phase plasma progesterone concentrations were measured in 12 female
      cynomolgus monkeys that were first socially housed, then individually housed, and
      finally returned to their original social groups. Afternoon heart rates increased
      during social separation compared to the social groupings (P < 0.001). Increased
      heart rates could not be explained by activity levels, which were lower during
      social separation than in social groupings (P < 0.001). Ovarian function (i.e.
      luteal-phase progesterone concentrations) was not influenced by housing
      condition. Single caging reduced the extent of social signaling, even though
      animals were in visual and auditory contact. Rates of affiliative behaviors
      increased and time spent alone decreased in post-reunion social groups compared
      to pre-separation social groups (P's < 0.01). The results indicate that chronic
      social separation in this group-living species may exacerbate atherosclerosis via
      altered autonomic activity, as evidenced by higher heart rates during social
      separation.

PMID- 9622270
TI  - Inhibitory effects of tranilast on expression of transforming growth factor-beta
      isoforms and receptors in injured arteries.
AB  - Tranilast (N(3,4-dimethoxycinnamoyl)anthranilic acid), an agent which in cell
      culture inhibits transforming growth factor-beta (TGF-beta) secretion and
      antagonises the effects of TGF-beta and platelet-derived growth factor (PDGF) on
      cell migration and proliferation, has been reported to reduce the incidence of
      restenosis after angioplasty in angiographically validated human clinical trials.
      We investigated in a rat model of balloon angioplasty whether tranilast's effects
      in vivo could be attributed to inhibition of expression of TGF-beta and/or its
      receptor types. Using a standardised reverse transcriptase-polymerase chain
      reaction (RT-PCR) assay, we examined the effects of three doses of tranilast (25,
      50 and 100 mg/kg) on the expression of two TGF-beta isoforms, the types I and II
      TGF-beta receptors and two putative TGF-beta responses, induction of integrins
      alpha(v) and beta3 mRNA, 2 h after oral administration and 26 h after vessel
      injury. Tranilast attenuated in a dose-dependent and reversible manner the injury
      induced increases in mRNA levels encoding TGF-beta1, TGF-beta3, two type I TGF
      beta receptors ALK-5 and ALK-2, and the type II receptor TbetaRII. At the highest
      dose mRNA levels encoding TGF-beta1 and TbetaRII were attenuated to levels
      approaching or below those observed in uninjured vessels. Messenger RNAs encoding
      TGF-beta3, ALK-5 and ALK-2 were all attenuated by between 70 and 74% (all P <
      0.05). Tranilast also attenuated in a reversible manner the elevations in mRNA
      levels for integrins alpha(v) and beta3 observed after vessel injury, by 90 and
      72%, respectively. We also investigated, in cultured smooth muscle cells derived
      from injured carotid arteries, the extent to which tranilast (300 mg/l)
      attenuated any increases in expression of type I and type II receptors stimulated
      by PDGF-BB and TGF-beta1, growth factors implicated in smooth muscle cell
      migration and proliferation in injured vessels. Increases in mRNA levels of the
      type I receptors ALK-5 and ALK-2 induced by PDGF-BB and TGF-beta1 were almost
      completely prevented by tranilast. Tranilast also prevented the PDGF-BB induced
      increases in TbetaRII but only partially inhibited the TGF-beta1 induced
      upregulation of TbetaRII. We conclude that tranilast can inhibit transcriptional
      mechanisms associated with the upregulation of TGF-beta and its receptor types in
      balloon catheter injured vessels. It is possible that these mechanisms contribute
      to its ability to reduce the frequency of restenosis after angioplasty.

PMID- 9622271
TI  - Fibroblast growth factor-2-toxin induced cytotoxicity: differential sensitivity
      of co-cultured vascular smooth muscle cells and endothelial cells.
AB  - Recombinant FGF-2-SAP is a mitotoxin consisting of the plant-derived ribosome
      inactivating toxin saporin (SAP) fused to basic fibroblast growth factor (FGF-2).
      FGF-2-SAP targets and kills cells bearing upregulated FGF receptors. In vivo, FGF
      2-SAP inhibits smooth muscle cell hyperplasia in models of restenosis. The
      present study examined the potential for a differential effect of FGF-2-SAP on
      canine vascular endothelial cells (EC) and smooth muscle cells (SMC) separately
      as well as in a novel co-culture model. Canine vascular SMC and EC cultures were
      established separately and made quiescent once cells reached 80% confluence.
      Following the release from growth arrest, both cell types were treated with FGF-2
      SAP, or FGF-2, or SAP alone for 48 h. [3H]TdR incorporation was used to determine
      the growth response of SMC and EC. The co-culture system was created by plating
      canine vascular SMC and EC on either side of a microporous 13 microm thick
      polyester membrane insert. Both cell types were grown to 80% confluence and
      independently made quiescent. Following the release from growth arrest, cells
      were treated with FGF-2-SAP, or FGF-2, or SAP alone. Negative and positive
      control groups were untreated wells containing phosphate buffered saline and
      complete growth media, respectively. After 48 h, both [3H]TdR incorporation and
      total DNA content, by fluorometric measurement, were quantitated in SMC and EC
      independently. FGF-2-SAP showed a concentration-dependent cytotoxicity in both
      canine SMC and EC but cytotoxicity for EC required substantially higher
      concentrations. In co-cultured SMC, FGF-2-SAP significantly decreased both
      [3H]TdR uptake and total DNA content at 0.5, 5, 50, and 500 ng/ml (0.01-10 nM)
      compared to positive controls. In co-cultured EC, FGF-2-SAP decreased [3H]TdR
      uptake at 50 and 500 ng/ml and total DNA content at 500 ng/ml compared to
      positive controls. Neither SAP alone nor FGF-2 alone showed a significant effect
      on [3H]TdR uptake or DNA content of either SMC or EC. In this unique co-culture
      model, which better replicates the relationship between SMC and EC in vivo, we
      demonstrated a dose-response range of FGF-2-SAP at which both the proliferation
      and total cell number of SMC, but not EC, is significantly reduced. These data
      suggest that FGF-2-SAP may have therapeutic utility in inhibiting myointimal
      hyperplasia in the absence of a deleterious effect on regenerating endothelium
      following vascular reconstructions.

PMID- 9622272
TI  - Divergent responses of the liver to increased delivery of glucose or fatty acids:
      implications for the pathogenesis of type IV hyperlipoproteinemia.
AB  - This study examines the patterns of response of primary cultures of hamster
      hepatocytes to increased delivery of glucose or oleate. Increased glucose in the
      medium produced: (1) increased triglyceride in the cells and the medium; (2) no
      change in cholesterol ester in the cells or the medium; (3) no change in apo B100
      secreted into the medium; (4) more apo B100 particles within the VLDL range with
      an increase in the VLDL triglyceride to apo B100 ratio. By contrast, increased
      oleate in the medium resulted in: (1) increased triglyceride in the cells and the
      medium; (2) increased cholesterol ester in the cells and the medium; and (3)
      increased apo B100 secreted into the medium. Important differences in the
      intracellular metabolism of triglyceride and cholesterol ester were also
      documented. Under all circumstances, there was substantially more radiolabelled
      triglyceride (overall eight times more) in the cell than in the medium,
      indicating that up to 90% of the newly synthesized triglyceride enters the
      cellular pool rather than being secreted with apo B100. By contrast, almost half
      of the newly synthesized cholesterol ester molecules were secreted with apo B100,
      pointing to an equal probability of entering the cell storage pool as opposed to
      being secreted. The data establish therefore two patterns of response of the
      liver to increased triglyceride synthesis depending on whether the substrate
      drive is glucose or oleate.

PMID- 9622273
TI  - Dexamethasone impairs cholesterol egress from a localized lipoprotein depot in
      vivo.
AB  - Plasma high density lipoproteins play a central role in the prevention and
      regression of atherosclerosis, as they are known to promote egress of cholesterol
      from cells. Glucocorticoids increase plasma HDL, but enhance esterification of
      cholesterol in macrophages in vitro. A novel model to measure cholesterol egress
      from a well defined depot in vivo was used currently to study the effect of
      dexamethasone on reverse cholesterol transport. Cationized LDL (cat LDL) (200
      microg cholesterol) was injected into the rectus femoris muscle of mice and the
      egress of cholesterol was studied as a function of time. Daily subcutaneous
      injection of dexamethasone (1.25 microg) raised plasma HDL levels by 40-80%. In
      mice injected with cat LDL labeled with 3H-cholesterol, daily treatment with
      dexamethasone slowed the loss of labeled cholesterol from the depot. With
      dexamethasone, there was no removal of the mass of lipoprotein cholesterol up to
      14 days after injection of cat LDL, while in the controls 75% of the exogenous
      cholesterol mass had been cleared from the depot. When the cat LDL had been
      labeled with 3H-cholesteryl ester (3H-CE), apparent hydrolysis of 3H-CE amounted
      to 46, 75 and 97% in controls, but only to 20, 48 and 65% in dexamethasone
      treated mice on days 4, 8 and 14, respectively. In addition, dexamethasone
      stimulated cholesterol re-esterification as evidenced by recovery of 80% of the
      retained cholesterol mass as CE. In experiments with cultured macrophages exposed
      to modified LDL, dexamethasone increased the amount of labeled cholesteryl ester
      by 50-75% as compared to controls. Histological examination of the rectus femoris
      muscle after injection of cat LDL showed that in dexamethasone treated mice
      cellular infiltration was sparser on day 4, but not on day 8, and persisted
      longer than in controls. In conclusion, dexamethasone treatment impeded
      cholesterol egress from a lipoprotein depot by: a) reduction of early inflow of
      mononuclear cells; b) partial inhibition of cholesteryl ester hydrolysis, and c)
      enhancement of cholesterol esterification. The latter effect did not permit
      cholesterol egress from the injected site even in the presence of high plasma HDL
      in dexamethasone treated mice.

PMID- 9622274
TI  - Delayed increase in high density lipoprotein-phospholipids after ingestion of a
      fat load in normolipidemic patients with coronary artery disease.
AB  - We studied the effect of a single oral fat load, supplemented with retinyl
      palmitate (RP), on high density lipoprotein (HDL) lipids in six normolipidemic
      men with coronary artery disease (CAD) and in six age- and lipid-matched
      controls. All subjects were selected from a study group which underwent the same
      protocol 2 years earlier. Post-prandial total plasma lipids, plasma RP levels,
      and HDL lipids were evaluated at 2-h intervals up till 10 h after the meal. In
      most subjects the post-prandial response of plasma triglyceride (TG) and plasma
      RP was identical in the first and second tests. Following the fat load, control
      subjects showed no change in HDL total cholesterol (TC) or HDL cholesteryl ester
      (CE) and showed an increase in HDL-TG. CAD subjects however showed a decrease in
      HDL-TC and HDL-CE and an increase in HDL-TG, similar to the increase in control
      subjects. In control subjects an increase in HDL phospholipid (PL) was apparent
      between 0 and 8 h after the fat load. By contrast, in CAD subjects the increase
      in HDL-PL was only found after as long as 6 h. The magnitude of the post-prandial
      response of HDL-PL measured during the test was significantly lower in the CAD
      group. The effects of the fat load on HDL free cholesterol (FC) were similar to
      the changes in HDL-PL. These data support the hypothesis that PL and FC released
      during the degradation of chylomicrons as surface remnants are taken up by HDL.
      This process is clearly delayed in normolipidemic CAD subjects compared with
      controls. The data suggest that differences in the post-prandial response to an
      oral fat load in normolipidemic CAD patients and control subjects are not
      confined to the clearance of TG-rich lipoproteins, but also involve a difference
      in the uptake of chylomicron surface material by HDL.

PMID- 9622275
TI  - Comparison of children and coronary heart disease patients with low high density
      lipoprotein cholesterol levels.
AB  - Low plasma high density lipoprotein cholesterol (HDL-C) is a major risk factor
      for coronary heart disease (CHD) in adults. In the field of pediatrics, subjects
      with low plasma HDL-C are often found among obese or dyslipidemic children.
      However, it is not clear whether low HDL-C in children should be considered a
      risk factor for CHD. The purpose of this study was to evaluate the risk for CHD
      in children with low HDL-C by comparing their lipid and apolipoprotein levels and
      physicochemical characteristics of their HDL with those of age-matched children
      with normal HDL-C and CHD patients with low HDL-C. Plasma lipids and
      apolipoproteins were measured in 206 dyslipidemic children (dyslipidemic), 65
      obese children (obese), 93 CHD patients with low HDL-C (< 40 mg/dl) and 128
      children with normal HDL-C (controls). To evaluate the physicochemical
      characteristics of HDL, molar and fractional esterification rates of cholesterol
      in plasma (MER(plasma) and FER(plasma)) and HDL (MER(HDL) and FER(HDL)) were
      determined in 128 children with normal HDL-C, 71 dyslipidemic, 33 obese and 93
      CHD who allowed second blood samples to be taken. Compared to controls, children
      with low HDL-C showed atherogenic profiles of lipid and apolipoprotein levels and
      physicochemical characteristics of HDL (lower apo A-I, lower ratio of apo A-I to
      apo B and higher FER(HDL)). Therefore, the differences in lipid and
      apolipoprotein profiles between children with low HDL-C and CHD patients with low
      HDL-C were examined next. The two groups of subjects based on the HDL-C level
      (Group I: < 30 mg/dl, Group II 30 < or = HDL-C < 40 mg/dl) were studied. Compared
      to CHD, Group I children showed less atherogenic apolipoprotein profiles (lower
      apo B and higher ratio of apo A-I to apo B). Similar findings were also found in
      Group II children, but the differences were less prominent than those in Group I
      children. FER(HDL) in children with low HDL-C were similar to those in CHD. These
      findings suggest that the physicochemical characteristics of HDL in children with
      low HDL-C are similar to those in CHD, but the abnormalities of apo B-containing
      lipoproteins are milder than those in CHD patients. Thus, if further changes in
      the nature of apo B-containing lipoproteins could be prevented, children with low
      HDL-C might not become high risk for CHD in later life.

PMID- 9622276
TI  - Free fatty acids modulate LDL receptor activity in BHK-21 cells.
AB  - It has been shown that dietary fatty acids affect serum low density lipoprotein
      (LDL) levels, but the mechanism responsible for this effect is still under
      debate. Here we investigate the effect of different free fatty acids on LDL
      receptor activity in BHK-21 cells. These cells possess a classical LDL receptor
      strongly regulated by substances like 25-OH-cholesterol or lovastatin.
      Preincubation of cells for 24 h with both oleic (cis 18:1) and its trans
      counterpart, elaidic acid, enhanced 125I-LDL binding, internalization and
      degradation, being oleic acid more effective than elaidic acid. Among
      polyunsaturated fatty acids (PUFA) of the n-6 series arachidonic acid (20:4)
      enhanced LDL receptor activity more than linoleic acid (18:2), and among PUFA of
      the n-3 series docosahexaenoic (22:6) and eicosapentaenoic acids (20:5) were more
      effective compared to alpha-linolenic acid (18:3). Conversely, preincubation of
      cells with saturated fatty acids, palmitic (16:0) and stearic (18:0) acids,
      decreased binding, internalization and degradation of 125I-LDL. Scatchard
      analysis of binding data obtained with palmitic and oleic acids showed that these
      two fatty acids affect LDL receptor number without altering receptor affinity.
      The regulatory effect of free fatty acids on LDL receptor activity in BHK-21
      cells is consistent with the hypothesis that the ability of fatty acids to
      modulate LDL-cholesterol levels in vivo is mediated, at least in part, by an
      action on receptor-dependent uptake of LDL.

PMID- 9622277
TI  - Remnants of chylomicron and very low density lipoprotein impair endothelium
      dependent vasorelaxation.
AB  - Remnants of chylomicron and very low density lipoprotein (VLDL) have been
      implicated as potentially atherogenic. Since endothelial dysfunction is an early
      event in atherosclerosis, we examined effects of the remnants on endothelium
      dependent vasorelaxation. The remnant lipoproteins were isolated from
      postprandial plasma in hyperlipidemic subjects using the immunoaffinity gel
      mixture of anti apo A-1 and anti apo B-100 monoclonal antibodies and
      ultracentrifugation. Rabbit aortic strips suspended in the organ chambers were
      incubated for 2 h with the preparations of lipoproteins and lipids. After
      incubation, the strips were tested with vasodilators after precontraction with
      phenylephrine (1 microM). The remnant lipoproteins (750-1500 microg
      triglyceride/ml) but not VLDL fraction (up to 1500 microg triglyceride/ml)
      impaired vasorelaxation in responses to acetylcholine, substance P and A23187.
      Carbamylated or methylated remnant lipoproteins, chemically modified remnant
      lipoproteins, had comparable impairment of the vasorelaxation as unmodified
      remnant lipoproteins. Incubation with lipid extracts from the remnant
      lipoproteins also exerted an inhibitory effect on the vasorelaxation. Relaxation
      to sodium nitroprusside was fully preserved in all aortas exposed to the
      lipoprotein preparations. Thus, the remnant lipoproteins impair endothelium
      dependent arterial relaxation at the concentrations observed in the plasma in
      patients with coronary artery disease (500-2000 microg triglyceride of remnant
      lipoprotein/ml). The impairment may be in apoprotein receptor-independent manner,
      and the lipids in the remnants seem to contribute to the inhibitory effect. The
      endothelial dysfunction caused by the remnant lipoproteins may play a role in the
      high prevalence of atherosclerotic coronary artery disease in postprandial
      hyperlipidemic patients.

PMID- 9622278
TI  - Lysophosphatidylcholine induces the production of IL-1beta by human monocytes.
AB  - There is evidence for the presence of lysophosphatidylcholine (lysoPC) in
      oxidatively modified low density lipoprotein, human plasma and in atherosclerotic
      lesions. We studied the effect of lysoPC on the cytokine production by human
      monocytes. Among all the cytokines tested (IL-8, TNF alpha, MCP-1 and IL-1beta),
      we found that lysoPC most consistently stimulated human monocytes to produce IL
      1beta in a dose and time dependent manner. Adherent monocytes were exposed to
      lysoPC in cell culture medium containing 0.5% bovine serum albumin. When exposed
      to lysoPC from 12.5 to 75 microM, the cellular content of IL-1beta increased 2-4
      fold. Up to a concentration of 50 microM no cytotoxic effect could be seen. Over
      50 microM there was evidence of toxicity. The level of IL-1beta reached its
      highest level at 24 h and then declined. At 48 h, the cell associated IL-1beta
      was low, but still the lysoPC stimulated cells produced 4.1 times more IL-1beta
      than controls. Also the IL-1beta mRNA was augmented by lysoPC in parallel with
      the IL-1beta protein levels. The stimulatory effect of lysoPC was dependent on
      its chain length. There was no effect on IL-1beta production when the acyl chain
      was shorter than 16. We also found that saturated lysoPC 18:0 stimulated IL-1beta
      production more than the monounsaturated lysoPC 18:1. Thus, the lysoPC in
      oxidatively modified LDL may stimulate the production of IL-1beta in macrophages,
      which may contribute to the inflammatory response in atherosclerotic tissue.

PMID- 9622280
TI  - Human apolipoprotein A-I gene promoter mutation influences plasma low density
      lipoprotein cholesterol response to dietary fat saturation.
AB  - Previous studies have shown that the A to G transition occurring at position -75
      bp upstream of the transcriptional start site in the human apolipoprotein A-I
      gene may affect plasma high density lipoprotein cholesterol (HDL-C) levels and
      low density lipoprotein cholesterol (LDL-C) response to changes in amount of
      dietary fat. We have examined the response to dietary fat saturation as a
      function of this mutation in 50 men and women. Subjects were first fed a
      saturated (SAT) fat diet (35% fat, 17% SAT) for 28 days, followed by a diet rich
      in monounsaturated fatty (MUFA) acids (35% fat, 22% MUFA) for 35 days and a diet
      rich in polyunsaturated (PUFA) fat (35% fat, 13% PUFA) for 35 days. All meals
      were prepared and consumed at the study sites. Lipoproteins were measured at the
      end of each diet period. The allele frequency for the A allele was 0.13. Subjects
      carrying the A allele had higher plasma cholesterol, LDL-C and triglyceride
      levels than those homozygotes for the G allele. As compared to the SAT diet, a
      PUFA diet induced significantly greater plasma total (P = 0.003) and LDL-C
      decreases (P = 0.001) in G/A women (-1.62 and -1.32 mmol/l, respectively) than in
      G/G subjects (-0.87 and -0.74 mmol/l for plasma and LDL-C, respectively).
      Multiple regression analysis demonstrated that in women, the variability in LDL-C
      response from a diet rich in SAT fat to a diet rich in PUFA was primarily due to
      LDL-C levels (during the SAT phase), accounting for 55.1% of the variance, waist
      to hip ratio (W/H; 11.4%) and the G/A polymorphism (10%). Whereas in men the
      major determinant of this response was smoking (21.4%). In conclusion, the G/A
      polymorphism appears to have a small but significant effect on plasma LDL-C
      responsiveness to changes in dietary fat saturation specially in women.

PMID- 9622281
TI  - Associations between skeletal muscle properties, physical fitness, physical
      activity and coronary heart disease risk factors in men.
AB  - High physical fitness and physical activity are associated with favourable lipid
      levels, especially a high level of high density lipoprotein cholesterol (HDL-C).
      A person's skeletal muscle properties, metabolism and percentage of different
      muscle fibres (ST-%), which may modify coronary heart disease (CHD) risk factors,
      such as serum insulin, obesity and serum sex hormones may also influence his
      fitness level and leisure-time physical activity. We studied the associations of
      physical fitness, physical activity and ST-% with serum lipids and lipoproteins
      in 72 healthy men. Their parameters were compared with those of 20 men with
      defined CHD. Significant interrelationships between ST-%, fitness and leisure
      time physical activity index (LTPAI) were observed. Multiple regression analysis
      showed that ST-%, fitness and leisure-time physical activity explained about 32%
      of the variation in HDL-C in the healthy men. In healthy men ST-% correlated
      positively with fitness (r(s) = 0.62, P < 0.001) and with LTPAI (r(s) = 0.62, P <
      0.001). Fitness level also correlated significantly with LTPAI (r(s) = 0.81, P <
      0.001). Serum insulin showed negative associations with ST-% (r(s) = -0.63, P <
      0.001) and fitness (r(s) = -0.54, P < 0.001) and LTPAI (r(s) = -0.62, P < 0.001).
      Free fraction of testosterone correlated negatively with serum HDL-C level (r(s)
      = -0.34, P < 0.01), with fitness (r(s) = -0.41, P < 0.001) and with LTPAI (r(s) =
      -0.54, P < 0.001). In sedentary men with the lowest fitness and physical activity
      the mean of ST-% (45%) was similar to that in CHD patients (44%). However, ST-%
      in men in the highest tertile of physical activity and fitness (68%) was
      significantly higher than in CHD patients and in men in the lowest tertile of
      physical activity and fitness. Skeletal muscle enzyme activity in lipid
      metabolism was significantly lower in both CHD patients and in sedentary and low
      fit men than that in fitter and physically active men. The present data imply
      that skeletal muscle properties are important determinants of risk profiles, such
      as physical activity, fitness and serum lipid and lipoprotein patterns. Although
      fitness is a graded, independent predictor of mortality from CHD, a relatively
      high fitness level is not enough. This was clearly observed in the clustering
      analysis, in which the healthy men, according to their ST-%, fitness, leisure
      time physical activity and serum sex hormone binding globulin (SHBG), fell into
      three natural groups: (i) Inactive men with lowest ST-% (mean 42%), lowest
      fitness (10.7 METs) and lowest HDL-C (1.36 mm/l); (ii) Fit men with high ST-%
      (66%), high fitness (14.5 METs) and moderately high HDL-C (1.54 mol/l); (iii)
      Active men with high ST-% (66%), highest fitness (14.9 METs) and highest serum
      HDL (1.83 mmol/l). The results support the idea that both fitness and physical
      activity give further protection against CHD by modifying risk factors. Our
      findings also suggest that skeletal muscle properties should be considered in the
      studies which assess CHD risk factors and their modifications especially in the
      field of health-related fitness.

PMID- 9622279
TI  - Oral estrogen improves serum lipids, homocysteine and fibrinolysis in elderly
      men.
AB  - The effects of estrogen on cardiovascular risk factors have been less well
      defined in men than in women. We measured lipid and lipoprotein concentrations,
      lipoprotein particle size distributions, lipoprotein (a), homocysteine, and
      markers of thrombosis and fibrinolysis in 18 [corrected] healthy elderly men (age
      74 +/- 3 years, mean +/- S.D.) before and after 9 weeks of treatment with 0.5, 1
      or 2 mg/day of oral micronized 17beta-estradiol. LDL-C (-6%), apo B (-9%),
      triglyceride (-5%), and homocysteine (-11%) concentrations decreased with
      estradiol, whereas HDL-C (+14%) increased. Intermediate-size VLDL subclass
      concentrations were lowered and LDL and HDL subclass levels altered in such a way
      as to cause average LDL and HDL particle size to increase. Lipoprotein (a) did
      not change. Fibrinogen (-13%) and plasminogen activator inhibitor-1 (PAI-1)
      concentrations (-26%) decreased, but there were no changes in thrombotic markers
      including thrombin-antithrombin III complex, prothrombin fragment 1.2, D-dimer,
      antithrombin activity, protein-C and S and von Willebrand factor antigen. Breast
      tenderness occurred in four men and heartburn in five but did not require
      discontinuation of treatment. We conclude that oral estrogen in men reduces
      homocysteine, fibrinogen, and PAI-1 concentrations and favorably influences VLDL,
      LDL and HDL subclass levels without increasing markers of thrombotic risk.

PMID- 9622282
TI  - Effects of a cardioselective beta-blocker on postprandial triglyceride-rich
      lipoproteins, low density lipoprotein particle size and glucose-insulin
      homeostasis in middle-aged men with modestly increased cardiovascular risk.
AB  - Beta-adrenergic receptor-blocking agents are commonly used for treatment of
      hypertension, angina pectoris and arrhythmias and as secondary prevention after
      myocardial infarction. The modest protection against myocardial infarction
      conferred by these compounds in primary-preventive studies has suggested that
      beneficial effects of beta-blockade are counteracted by known adverse influences
      on lipid and glucose metabolism. As most beta-blockers increase plasma
      triglycerides and decrease the high density lipoprotein (HDL) cholesterol
      concentration, a randomized, double-blind, cross-over study was conducted to
      evaluate whether a 12-week treatment with metoprolol (100 mg o.d.) or placebo
      affected the metabolism of postprandial triglyceride-rich lipoproteins in 15
      middle-aged men with a modestly increased cardiovascular risk. Metoprolol
      treatment significantly increased the postprandial responses of very low density
      lipoprotein (VLDL) and VLDL remnants to a mixed meal-type of oral fat tolerance
      test. The effect was particularly prominent for larger (Svedberg flotation rate
      (Sf) > 400 and Sf 60-400) particle species (P < 0.001 in repeated measures
      ANOVA), whereas the smaller (Sf 20-60) particles were less affected (P < 0.05).
      The changes in the postprandial responses of the different VLDL species were
      mainly related to an effect on the fasting plasma concentrations, with limited or
      no influences on VLDL catabolism during the postprandial state. In contrast,
      metoprolol treatment did not significantly influence the postprandial responses
      of chylomicrons and chylomicron remnants. Notably, the enhanced fasting and
      postprandial triglyceridaemia during metoprolol treatment was neither accompanied
      by a rise in fasting or postprandial free fatty acid concentrations, nor by
      alterations of the glucose and insulin responses to a standard oral glucose
      challenge. The ensuing shift in the LDL particle size distribution towards
      smaller particles was limited (fraction small LDL: metoprolol 22.8 +/- 15.7%
      versus placebo 19.3 +/- 15.0%, P < 0.05). In conclusion, metoprolol treatment
      primarily enhances fasting and postprandial triglyceridaemia in middle-aged men
      by increasing the basal hepatic production of VLDL.

PMID- 9622283
TI  - Treatment of severe hypertriglyceridemia lowers plasma viscosity.
AB  - Elevated plasma viscosity is a predictor of atherosclerotic vascular disease and
      is a potential mechanism by which hypertriglyceridemia increases cardiovascular
      risk. Previous studies of plasma viscosity reduction in hypertriglyceridemic
      patients used medications that lowered both triglyceride and fibrinogen levels.
      Because fibrinogen is a major determinant of viscosity, it is unclear whether
      triglyceride reduction alone is sufficient to reduce plasma viscosity. The
      purpose of this study was to determine whether triglyceride-lowering therapy
      reduces plasma viscosity. This was a prospective study of 24 adult patients with
      severe hypertriglyceridemia (> or = 5.67 mmol/l). Fasting lipid, total serum
      protein, fibrinogen, plasma viscosity and serum viscosity levels were measured
      before and after therapy with 1200 mg/d of gemfibrozil. Triglyceride levels
      decreased by 70% (P < 0.001). Mean plasma and serum viscosity levels decreased by
      0.082 mPa/s (P = 0.003) and 0.086 mPa/s (P = 0.013), respectively. Fibrinogen
      levels did not change significantly. Triglyceride-lowering therapy reduced plasma
      and serum viscosity without changes in fibrinogen levels. Since serum samples are
      deplete of fibrinogen, the serum viscosity reduction observed is corroborative
      evidence for an independent effect of triglyceride-lowering therapy on plasma
      viscosity. This observation provides a physiological rationale for triglyceride
      lowering therapy in patients at risk for atherosclerotic vascular disease, the
      chylomicronemia syndrome and pancreatitis.

PMID- 9622284
TI  - In search of a biological pattern for human longevity: impact of apo A-IV genetic
      polymorphisms on lipoproteins and the hyper-Lp(a) in centenarians.
AB  - We studied centenarians to investigate the biological basis of human longevity
      focusing on the apolipoprotein A-IV and lipoprotein(a), potentially involved in
      the susceptibility to atherogenic mechanisms. We analyzed two restriction
      polymorphisms, HinfI347 (alleles +, -) and Fnu4HI360 (alleles 1, 2), and a VNTR
      (alleles 3, 4) at the 3' region of the apo A-IV gene. The allele frequencies, the
      lipoprotein concentrations and their association in centenarians and adults have
      been compared. In centenarians, the HinfI genotype distribution is different (P <
      0.05) and the (+13) haplotype is prevalent (0.54 vs. 0.39), with a greater
      association of (+3), indicating the selection of a favourable allele. The
      lipoprotein modulation by the apo A-IV polymorphisms is suggested by significant
      associations in adults ((+/+) homozygotes have lower LDL-cholesterol and apo B
      than heterozygotes; (1/1) homozygotes have higher TG and apo B than
      heterozygotes), that in centenarians still exists as a trend. Centenarians show
      peculiar lipoprotein features: lower LDL-cholesterol (mean 103 vs. 115 mg/dl; P <
      0.02), and higher lipoprotein(a) (median 17.5 vs. 4.5; P < 0.002). Large part of
      them (47%), especially the Hinf(+/+) and the (+13) homozygotes, have a
      lipoprotein(a) > 20 mg/dl, value considered as the threshold for atherogenic
      risk, surprisingly compatible with healthy longevity.

PMID- 9622285
TI  - One-year treatment with ethyl esters of n-3 fatty acids in patients with
      hypertriglyceridemia and glucose intolerance: reduced triglyceridemia, total
      cholesterol and increased HDL-C without glycemic alterations.
AB  - n-3 Fatty acids in the form of ethyl esters (EE) allow lower daily doses and
      improved compliance. Administration of n-3 fatty acids to patients with glucose
      intolerance has led to controversial findings, some studies indicating worsening
      of the disorder, others no effect, or an improvement. A total of 935 patients
      with hypertriglyceridemia, associated with additional cardiovascular risk
      factors, i.e. glucose intolerance, NIDDM and/or arterial hypertension were
      entered a double blind (DB) protocol lasting 6 months with n-3 EE versus placebo,
      followed by a further 6 months of open study (n = 868) on 2 g a day of n-3 EE. At
      the end of the DB period, triglyceridemia in the total group was reduced
      significantly more by n-3 EE, without alterations in glycemic parameters. In the
      6 months open follow up, patients on n-3 EE with type IIB hyperlipoproteinemia
      showed a significant reduction of total cholesterol, both in cases with (-4.15%
      vs. the 6 month levels) and without NIDDM (-3.8%). HDL-cholesterol had an overall
      mean rise of 7.4%, maximal in type IV patients with (+9.1%) and without (+10.1%)
      NIDDM. No alterations in glycemic parameters were detected in treated patients.
      Administration of n-3 EE to patients with hypertriglyceridemia associated with
      NIDDM or impaired glucose tolerance appears safe and effective.

PMID- 9622286
TI  - Oxidation resistance of LDL is correlated with vitamin E status in beta
      thalassemia intermedia.
AB  - The alteration of the oxidant/antioxidant balance may affect the susceptibility
      of low density lipoproteins (LDL) to oxidation in haemolytic disorders such as
      thalassemia. Thirty patients affected by beta-thalassemia intermedia were
      examined, and compared with age-matched healthy controls. The mean amount of
      vitamin E in the thalassemic LDL was lower than control (p < 0.0001), either when
      it was calculated on the base of LDL protein (61% decrease) or cholesterol (25%
      decrease). The LDL resistance to Cu2+-induced oxidation, evaluated as the length
      of the lag phase before the onset of conjugated diene (CD) lipid hydroperoxide
      production, was 20% lower than control. Other parameters of LDL susceptibility to
      oxidation, such as the rate of lipid peroxidation, Rp, and the total amount of
      conjugated dienes produced, CDmax, were only slightly lower than control, which
      can be explained by a lower content of peroxidable lipids in the thalassemic LDL.
      Total LDL cholesterol was 1.08 x 10(3) and 2.07 x 10(3) mol/mol LDL in
      thalassemic and in control LDL, respectively. The length of the lag phase in
      thalassemic LDL shows a strongly positive correlation with its vitamin E content
      (r = 0.732; p < 0.0001). The r2-value of 0.53 provides evidence that more than
      50% of the lag phase is determined by vitamin E. Oxidizability of LDL lipids may
      explain 22-24% of the lag phase, as calculated by the inverse correlation between
      the length of the lag phase and CDmax (r = -0.474; p = 0.008; r2 = 0.22) and Rp
      (r = -0.499; p = 0.005; r2 = 0.24). In multiple regression analysis, the lag
      phase was predictable to 66% by vitamin E plus CDmax, and to 60% by vitamin E
      plus Rp. Plasma vitamin E was 53% lower in thalassemia patients compared to
      control and positively correlated with vitamin E in the LDL (r = 0.677; p <
      0.0001). None of the correlations above were observed in control subjects. In
      conclusion, beta-thalassemia is associated with very low levels of vitamin E in
      plasma and in LDL, a condition that renders these particles more susceptible to
      in vitro oxidative modification and may account for atherogenesis-related
      vascular diseases described in thalassemia. The present data on a statistically
      significant correlation between abnormally low vitamin E and oxidizability of LDL
      contribute substantially to the hypothesis that vitamin E is a
      pathophysiologically important determinant of antioxidative protection of LDL.

PMID- 9622287
TI  - Decrease in fibrinogen and LDL-cholesterol levels upon supplementation of diet
      with Lactobacillus plantarum in subjects with moderately elevated cholesterol.

PMID- 9622288
TI  - From the history of investigations on the oxidative modification of small dense
      LDL.

PMID- 9622289
TI  - Hyperlipidemia and serum complement.

PMID- 9622290
TI  - Copper deficiency and lipoprotein oxidation.

PMID- 9622291
TI  - Gene regulation of growth hormone-releasing hormone and its receptor.

PMID- 9622292
TI  - Thyroid-specific transcription factors.

PMID- 9622293
TI  - Distribution and fine structure of macrophages in the human ovary during the
      menstrual cycle, pregnancy and menopause.
AB  - We evaluated the distribution and ultrastructural characteristics of macrophages
      in the ovaries of women of reproductive ages, during pregnancy, and after
      menopause, by immunohistochemistry and transmission electron microscopy.
      Macrophages appeared around the ovarian follicle with its development. Their
      organelles were poorly developed, and no vacuoles or granules were observed in
      the cytoplasm. Macrophages were also present in the cavity of the atretic
      follicle, being larger in size than those in the developing follicle and
      characterized by cytoplasmic vacuoles and granules of a lysosomal nature. With
      the luteinization of the follicle, macrophages were seen to be distributed inside
      and outside the corpus luteum, but constituted only a minor population as
      compared with other kinds of leukocytes. The intracellular organelles were well
      developed, including the lysosomal granules. In early pregnancy, the number of
      macrophages was noticeably increased in the corpus luteum. They were observed
      mainly outside the corpus luteum, and stained strongly with hCG
      immunohistochemically. Macrophages were present in the regressing corpus luteum
      and in the corpus albicans. Numerous lipid droplets and elongated cholesterol
      crystals were seen in the cytoplasm. Macrophages therefore appeared to be present
      throughout the ovarian cycle and may be involved in the development and atresia
      of the follicles and the progression and the regression of luteal tissues.

PMID- 9622294
TI  - Role of interleukin-1beta in superovulation in rats.
AB  - In this study, the changes in interleukin-1beta (IL-1beta) mRNA expression and
      its localization in the ovary were studied in pregnant mares' serum gonadotropin
      (PMSG)-human CG (hCG) injected immature rats. Moreover, to study the in vivo role
      of IL-1 during ovulation, the IL-1 receptor antagonist (IL-1ra) was injected into
      the bilateral bursae (100 microg/15 microl/bursa) immediately or at the 3rd, 5th,
      10th h after hCG injection. IL-1beta mRNA expression in the ovary had
      significantly (P<0.05) increased at the 6th h after hCG injection, and its level
      depended on the time interval between PMSG and hCG injections; the maximal IL
      1beta mRNA expression was observed when hCG was injected 48 h after the PMSG
      injection. The signals of IL-1beta mRNA localized in the thecal layer,
      particularly in the large preovulatory follicles. Intrabursal IL-1ra injection at
      the 3rd h after hCG injection showed a trend toward lowering the number of ova
      shed, and the injection at the 5th h significantly (P<0.01) decreased the number
      of ova shed compared with the saline injected control group. At the 24th h after
      hCG injection, there were a few large preovulatory follicles with distinguishable
      theca and granulosa layers in the IL-1ra treated ovary, although these two layers
      were indistinguishable in the control ovary. These results indicated that IL
      1beta mRNA expression was definitely induced by hCG stimulation, and, moreover,
      this expression was dependent on the stage of follicular maturation. IL-1 may be
      important for the ovulation in the superovulatory cycle by PMSG in rats.

PMID- 9622295
TI  - A case of mitochondrial encephalomyopathy, lactic acidosis and stroke-like
      episodes associated with diabetes mellitus and hypothalamo-pituitary dysfunction.
AB  - A 45-year-old woman with mitochondrial encephalomyopathy, lactic acidosis and
      stroke-like episodes (MELAS) had muscular atrophy, severe cerebral and cerebellar
      atrophy, and cardiac hypertrophy. She also had diabetes mellitus treated with
      insulin, and sensorineural hearing loss. Ragged-red fibers were observed on
      muscle biopsy and an adenine to guanine transition mutation at position 3243 of
      her mitochondrial DNA was confirmed. Further investigations revealed that she
      also had hypothalamo-pituitary dysfunction. It appears that diabetes mellitus,
      hypothalamo-pituitary dysfunction, and the other abnormalities are all associated
      with mitochondrial dysfunction in this patient.

PMID- 9622296
TI  - Effects of growth hormone-releasing hormone (GRF) analogs, bovine and rat GRF on
      growth hormone secretion in cattle in vivo.
AB  - Effects of bovine and human growth hormone-releasing hormone (GRF) analogs
      (bGRF(1-29)-NH2: bGRF-29, [D-Ala2, Ala15]-bGRF-29, [D-Ala2]-hGRF(1-29)-NH2: [D
      Ala2]-hGRF-29), bovine GRF (bGRF(1-44)-NH2: bGRF-44), as well as rat GRF (rGRF)
      on GH release were studied in female calves. Intravenous (i.v.) bolus injections
      of 0.25 microg/kg BW of bGRF-29, [D-Ala2, Ala15]-bGRF-29, and [D-Ala2]-hGRF-29
      stimulated GH release. Plasma GH levels began to rise 10 min after the injection
      of each peptide, and significant increases in GH concentrations were obtained at
      60, 180 and 150 min after the injection of bGRF-29, [D-Ala2, Ala15]-bGRF-29 and
      [D-Ala2]-hGRF-29, respectively. The concentrations of GH 80 min after the
      injection of [D-Ala2, Ala15]-bGRF-29 were significantly higher than those after
      the injection of [D-Ala2]-hGRF-29 (except at 80 and 90 min) or bGRF-29. The i.v.
      bolus injections of 0.25 microg/kg BW of bGRF-44 and rGRF stimulated GH release,
      and the GH-releasing potency of rGRF was approximately equal to that of bGRF-44.
      The plasma GH responses to the repeated i.v. injection of bGRF-29 or [D-Ala2,
      Ala15]-bGRF-29 at 2-h intervals were examined. bGRF-29 acutely increased plasma
      GH levels after each injection, and the high GH levels decreased to the basal
      values within 2 h. In contrast, high GH levels induced by [D-Ala2, Ala15]-bGRF-29
      were gradually decreased but not lowered to basal values throughout the
      experiment. These results show that [D-Ala2, Ala15]-bGRF-29 has longer-lasting
      and greater GH-releasing activity than the other GRF analogs in female calves,
      and the GH-releasing potency of rat GRF is approximately equal to that of bovine
      GRF in cattle in vivo.

PMID- 9622297
TI  - Bihormonal cells secreting both prolactin and gonadotropins in normal rat
      pituitary cells.
AB  - The present study was designed to characterize bihormonal cells in rat pituitary
      cells which secrete PRL and gonadotropins. This was done by using sandwich cell
      immunoblot assay (CIBA) and reverse hemolytic plaque assay (RHPA) in combination
      with immunocytochemistry (ICC) and by measuring the intracellular free calcium
      concentration ([Ca2+]i). The result of the experiment with sandwich CIBA revealed
      that the populations of LH- and FSH-secreting cells in the PRL-secreting cells
      were 6.23% and 5.91%, respectively, and the populations of the PRL secreting
      cells in the LH- and FSH-secreting cells were 18.4% and 15.5%, respectively.
      Additional studies by the combined techniques of RHPA with ICC revealed that the
      populations of LH- and FSH-containing cells in the PRL secreting cells were 4.43%
      and 2.40%, respectively, which were consistent with the results of Sandwich CIBA.
      Some of the PRL-secreting cells determined by RHPA showed responsiveness to TRH
      and GnRH in [Ca2+]i. These results suggest that bihormonal cells which secrete
      both PRL and LH, or both PRL and FSH are present in the normal rat pituitaries.

PMID- 9622298
TI  - Effects of short- and long-term dexamethasone treatment on growth and growth
      hormone (GH)-releasing hormone (GRH)-GH-insulin-like growth factor-I axis in
      conscious rats.
AB  - Although the inhibitory effects of a chronic excess of glucocorticoids (GC) on
      body growth and GH secretion are well established, the mechanisms involved remain
      unclear. In this study, we examined the chronic effects of a high dose of
      dexamethasone (DEX) on spontaneous GH secretion and insulin-like growth factor
      (IGF)-I in conscious rats. The animals were given daily i.p. injections of DEX
      (200 microg/day) for either one or four weeks. Body growth assessed by tibia
      length and serum IGF-I levels was significantly inhibited 1 week after treatment.
      By contrast, spontaneous GH secretion was not altered 1 week after the treatment.
      Neither hypothalamic GRH and somtatostain mRNA levels nor GH responses to GRH
      from single somatotropes were affected 1 week after the treatment. Four weeks
      after DEX treatment, body growth of the rats was noticeably suppressed.
      Interestingly, spontaneous GH secretion, hypothalamic GRH mRNA levels and GH
      responses to GRH were all inhibited 4 weeks after treatment. Pituitary GRH
      receptor mRNA levels were not altered 1 week after treatment, but increased after
      4 weeks. These results indicate that a high dose of DEX initially impairs IGF-I
      production and subsequently inhibits spontaneous GH secretion in rats. Inhibition
      of spontaneous GH secretion resulting from chronic GC excess is due, at least in
      part, to the impairment of hypothalamic GRH synthesis and pituitary GH
      responsiveness. An increase in the pituitary GRH receptor may be caused by
      decreased GRH secretion.

PMID- 9622299
TI  - Molecular cloning of quail thyroid-stimulating hormone (TSH) beta subunit.
AB  - Thyroid-stimulating hormone (TSH) beta subunit cDNA was obtained from Japanese
      quail (Coturnix japonica) by PCR and its nucleotide sequence was determined. The
      cDNA encodes a putative signal peptide and a mature protein consisting of 20 and
      114 amino acids, respectively. The amino acid sequence of quail TSHbeta subunit
      shows homologies of 67-69% in mammalian species, 58% in amphibian and 43-49% in
      teleost fish. Comparison of the amino acid sequence with TSHbeta subunits of
      other species reveals some differences in several regions responsible for its
      biological functions and characteristic features of the avian TSHbeta subunit,
      suggesting that the functional domains have diverged cooperatively between the
      hormone and its receptor during evolution.

PMID- 9622300
TI  - Multiple endocrine neoplasia type 1 is not rare in Japan.
AB  - Multiple endocrine neoplasia type 1 (MEN 1) is rarely reported in Japanese and
      other oriental populations. To examine if there is a racial difference in the
      prevalence of MEN 1, we initiated extensive work on patients with endocrine
      tumors for additional lesions, and annual screening of family members of affected
      patients. In a four-year study, eleven asymptomatic patients were found by family
      screening, and the number of patients with MEN 1 in our clinics increased from 16
      to 38. Estimated prevalence of MEN 1 was no less than 0.018/1000. MEN 1 may not
      be as rare as had been thought in Japanese, and the prevalence of MEN 1 in
      Japanese would not be significantly different from that of Caucasians. Systemic
      surveillance and extensive screening of family members are required for early
      detection and management of patients.

PMID- 9622301
TI  - 3Beta-hydroxysteroid dehydrogenase activity in human osteoblast-like cells.
AB  - This paper describes for the first time the presence of 3beta-hydroxysteroid
      dehydrogenase (3beta-HSD) activity in osteoblast-like cells and investigates its
      characteristics. 3beta-HSD activity was detected by the formation of
      androstenedione from [3H]dehydroepiandrosterone (DHEA) in whole cell assays of
      human osteoblast-like cells, HOS and MG-63. The radiolabeled product,
      androstenedione, was purified by thin-layer chromatography and identified by
      recrystallization on admixture with authentic androstenedione to show constant
      specific activities. The apparent Michaelis constant (Km) for DHEA in HOS was
      found to be 9.9 microM and that in MG-63 was 80.4 microM. The expression of the
      3beta-HSD messenger ribonucleic acid in HOS and MG-63 was demonstrated through a
      reverse transcription-polymerase chain reaction. The PCR products were confirmed
      by Southern blot analysis. The existence of 3beta-HSD in osteoblast-like cells
      indicates that these cells convert delta5 androgens into more biologically active
      delta4 3-keto steroids. These results, together with the demonstration of other
      steroid converting enzyme systems, suggest that the osteoblast cells play an
      important role in facilitating hormonal action in bone tissue.

PMID- 9622302
TI  - Appearance of TSH receptor antibody and hyperthyroidism associated with
      metastatic thyroid cancer after total thyroidectomy.
AB  - We report here on a patient who was diagnosed with follicular carcinoma in 1985,
      and who was treated with total thyroidectomy. Two years later, when metastasis
      was found in his neck lesion, lung, pelvis and right femur, the patient received
      131I treatment. Six years after receiving 131I treatment, the patient presented
      with hyperthyroidism. Whole-body scan with 131I revealed functioning metastasis
      in his right femur and pelvis. There was no hot spot in the neck region,
      confirming that no thyroid tissue remained. Blood panels revealed an increase in
      both TSH binding inhibitory immunoglobulin (TBII. 36.2%; normal. -10
      approximately 10%) and thyroid stimulating antibody (TSAb, 176%; normal, less
      than 145%). Treatment with antithyroid drugs, dexamethasone and radioisotope
      therapy rapidly resolved his hyperthyroidism. Thyrotoxicosis and positive TRAb
      occurred in the absence of thyroid tissue, and many years after the completion of
      R1 therapy. The overproduction of thyroid hormone can therefore only be
      attributed to some mechanism of activity in the metastatic tumor tissue.

PMID- 9622303
TI  - Effects of muscarinic and adrenergic blockade on growth hormone secretion induced
      by growth hormone-releasing peptide-2 (GHRP-2) in ovariectomized ewes.
AB  - This study was performed to investigate whether the blockade of cholinergic
      muscarinic and adrenergic pathways was involved in the GH-releasing effect of GH
      releasing peptide-2 (GHRP-2) in ovariectomized ewes. Cholinergic muscarinic
      antagonist, atropine (0.2 mg/kg, i.v., 15 min before GHRP-2 administration)
      blunted the GH secretion caused by GHRP-2 (12.5 microg/kgBW). alpha-Adrenergic
      antagonist phentolamine (15 microg/kgBW x min, infusion from -15 to 30 min) did
      not affect the GH response to GHRP-2, and beta-adrenergic antagonist propranolol
      (0.25 mg/kgBW, i.v., 15 min before GHRP-2 administration) did not suppress the
      GHRP-2-induced GH release. These results showed that cholinergic muscarinic
      antagonist agent, atropine, exerts an inhibitory effect on GHRP-2-induced GH
      secretion in ovariectomized ewes.

PMID- 9622304
TI  - Gene expressions of keratinocyte growth factor and its receptor in the human
      endometrium/decidua and chorionic villi.
AB  - Keratinocyte growth factor (KGF) is secreted from mesenchymal fibroblasts and has
      a mitogenic specificity for epithelial cells in a paracrine fashion. In order to
      clarify the biological significance of KGF in the human endometrium which
      undergoes dynamic changes under the influence of sex steroid hormone, we
      investigated the gene expressions of KGF and its receptor (KGF-R) in the human
      endometrium in various sex steroid hormone milieus and chorionic villi, by RT-PCR
      and Northern blot hybridization. The secretory phase endometrium had a KGF mRNA
      level 10-fold greater than that of the proliferative phase endometrium. Similarly
      abundant KGF mRNA was found in decidua and pseudopregnant endometrium compared
      with proliferative phase endometrium. The KGF-R mRNA was detected by RT-PCR in
      chorionic villi from early pregnancy. These results indicate that the gene for
      KGF expressed in the human endometrium is mainly regulated by progesterone and
      that KGF might have a role in the interaction between decidua and chorion in
      early pregnancy in man.

PMID- 9622305
TI  - Potentiation of ejaculatory activity by median raphe nucleus lesions in male
      rats: effect of p-chlorophenylalanine.
AB  - The effect of radiofrequency lesions in the median or dorsal raphe nucleus (MRL
      or DRL) on copulatory behavior was examined in sexually inexperienced male rats.
      Three weeks after castration and the brain surgery, all males were subcutaneously
      implanted with Silastic capsules containing testosterone. In the first behavioral
      test, the frequency of ejaculation in the MRL group was significantly higher than
      that in sham and DRL males, but mount and intromission were not. Seven days after
      the first test, the second test was carried out after treatments with 100 mg/kg p
      chlorophenylalanine (PCPA), a serotonin synthesis inhibitor, or saline daily for
      4 days in MRL and DRL males. The frequencies of male sexual behavior in PCPA
      treated DRL males were higher than those in saline treated DRL males. In
      contrast, even after treatments with PCPA, male sexual activity in MRL males was
      comparable to those in saline treated MRL males. These results suggest that
      serotonergic neurons in the median raphe nucleus play an inhibitory role in the
      regulation of male sexual activity, especially ejaculation. Furthermore, it can
      be thought that PCPA acts on the median raphe neurons and facilitates ejaculatory
      behavior.

PMID- 9622306
TI  - Occurrence and spontaneous remission of Graves' hyperthyroidism preceded by
      painless thyroiditis.
AB  - A 45-year-old woman was referred to our hospital because of discomfort in the
      cervical region. Laboratory findings revealed thyrotoxicosis with positive TSH
      receptor antibodies, but acute inflammatory data were absent. After three weeks
      the thyroid hormone levels spontaneously decreased to hypothyroid levels, and
      thyroidal radioactive iodine uptake (RAIU) was below normal. A needle-biopsy
      specimen of the thyroid gland obtained two months later showed diffuse
      lymphocytic thyroiditis, and she was therefore diagnosed as having had painless
      thyroiditis. Two months after returning to euthyroidism, a second thyrotoxicosis
      developed. TSH receptor antibodies remained positive, but RAIU was slightly above
      normal, indicating Graves' hyperthyroidism. Treatment with antithyroidal drugs
      was commenced but was soon discontinued due to an allergic reaction. Although
      only beta-adrenergic antagonist was administered for treating the thyrotoxicosis,
      thyroid function was gradually normalized in parallel with the reduction in TSH
      receptor antibody. In this case, painless thyroiditis would be followed by
      Graves' disease and subsequent spontaneous remission.

PMID- 9622307
TI  - Manifestation of primary hyperthyroidism after pituitary adenomectomy: a case
      report.
AB  - We report a 47-year-old Japanese man who presented with visual disturbance due to
      a pituitary tumor with suprasellar extension. The patient had mild secondary
      hypothyroidism preoperatively, and was started on administration of levothyroxine
      sodium immediately before transsphenoidal surgery. After the operation,
      levothyroxine sodium was continued for several months. Pathological examination
      of the surgical specimen, together with endocrinological investigation revealed
      that the suprasellar tumor was a FSH-producing pituitary adenoma. Since 3 months
      after the operation, he has developed muscle weakness and finger tremor. He was
      found to be thyrotoxicosis, and levothyroxine sodium was discontinued. Seven
      weeks after levothyroxine sodium was discontinued, thyrotoxicosis continued, with
      a positive thyrotropin binding inhibitory immunoglobulin (TBII) and a high
      diffuse 123I-uptake by the thyroid. He was started on thiamazole 30 mg/day.
      Although his thyroid dysfunction improved within 2 months, hyperthyroidism
      worsened repeatedly on attempts to discontinue thiamazole, and he required
      continuous treatment at 2.5 mg/day. Patients with occult autoimmune thyroiditis
      rarely progress to thyrotoxicosis after operations on other endocrine organs such
      as the adrenal or parathyroid gland. In patients with pituitary adenoma, thyroid
      function and thyroid-associated autoantibodies should be investigated pre- and
      post-operatively.

PMID- 9622308
TI  - Possible involvement of calcium/calmodulin-dependent protein kinase in ACTH
      induced expression of the steroidogenic acute regulatory (StAR) protein in bovine
      adrenal fasciculata cells.
AB  - Steroidogenic acute regulatory (StAR) protein plays a crucial role in the
      regulation of cholesterol transport from the outer mitochondrial membrane to the
      inner membrane, where P450scc participates in a rate-limiting step of adrenal
      steroidogenesis. We have already reported that both of cAMP- and protein kinase C
      dependent processes may play a crucial role in the regulation of expression of
      StAR protein when bovine fasciculata cells are stimulated with ACTH. In the
      present study, ACTH increased cytosolic calcium movement and activated expression
      of StAR protein, resulting in enhancing cortisol production by bovine adrenal
      fasciculata cells. The role of the calcium/calmodulin-dependent protein kinase
      process in the regulation of expression of the StAR protein by ACTH was studied.
      The activating effects of ACTH on the StAR protein and cortisol production were
      inhibited by pretreatment with KN-93, a specific inhibitor of calcium/calmodulin
      dependent protein kinase II. These findings suggest that ACTH can enhance
      expression of the StAR protein as well as cortisol synthesis in bovine adrenal
      fasciculata cells, in part via a calcium/calmodulin-dependent protein kinase
      process.

PMID- 9622309
TI  - Comparative studies on the initiation of labor.
AB  - Parturition is a multifactorial physiological process that involves multiple
      interconnected positive feedforward and negative feedback loops. Each of these
      loops is connected to others in a carefully time-regulated fashion. When
      parturition occurs normally, both fetal and maternal processes are involved.
      Recent research in pregnant sheep and nonhuman primates shows clearly that the
      fetus determines the duration of gestation and the mother determines the time of
      day at which labor begins. The fetal hypothalamo-pituitary-adrenal axis plays a
      fundamental role in stimulating increased estrogen production in late gestation.
      Estrogen then activates maternal circadian rhythms that increase oxytocin
      secretion. As a result, uterine contraction patterns are switched from
      contractures to contractions.

PMID- 9622310
TI  - Electronic fetal monitoring: a brief summary of its development, problems and
      prospects.
AB  - Electronic fetal monitoring (EFM) was introduced into clinical practice 30 years
      ago and spread very rapidly in most developed countries. The early optimism that
      EFM would lead to a marked reduction in fetal neurological injury has not been
      realized; however, it is now recognized that most such damage is unrelated to
      perinatal events. Clinical trials have shown that although EFM does reduce the
      incidence of intrapartum asphyxia, its use is also associated with an increase in
      cesarean sections. Abnormal fetal heart rate (FHR) patterns are poor predictors
      of fetal depression at birth when used without additional confirmatory
      information. An additional problem has been inconsistency in the interpretation
      of EFM tracings even among experts. This has reduced the clinical effectiveness
      of EFM and has also contributed to an increase in litigation in cases with
      adverse neonatal outcomes. Despite these shortcomings EFM continues to be used
      extensively on most obstetrical services, suggesting that obstetrical physicians
      and nurses find the technique helpful and will continue to use it until a better
      alternative comes along. The combination of relevant clinical data with EFM by
      means of intelligen computer systems may improve both the consistency and
      predictive value of intrapartum fetal assessment in the future.

PMID- 9622311
TI  - Maternal regulation of fetal development and health in adult life.
AB  - Babies who are small or disproportionate at birth, or who have altered placental
      growth are now known to have increased rates of coronary heart disease,
      hypertension and non-insulin-dependent diabetes in adult life. These associations
      are thought to result from fetal 'programming', whereby a stimulus or insult at a
      critical, sensitive period of early life has permanent effects on the body's
      structure, physiology and metabolism. Small size at birth and disproportion in
      head size, length and weight appear to be surrogate markers for the actual
      influences that programme the fetus. These observations have prompted a re
      evaluation of the maternal regulation of human fetal development. Recent studies
      suggest that the fetus may be considerably more sensitive to the materno
      placental supply of nutrients than hitherto imagined. Adult cardiovascular
      disease may be a consequence of fetal adaptations invoked when the materno
      placental nutrient supply fails to match the fetal nutrient demand. Understanding
      the maternal regulation of human fetal development could lead to public health
      measures that improve the adult health of future generations.

PMID- 9622312
TI  - Periconceptional folic acid containing multivitamin supplementation.
AB  - OBJECTIVE: A summary about the final results of the Hungarian double-blind
      placebo controlled randomised trial of periconceptional folic acid containing
      multivitamin and trace element supplementation. RESULTS: The major finding is a
      significant prevention of the first occurrence of neural-tube defect, urinary
      tract and cardiovascular defects, in addition a decrease in the rate of limb
      deficiencies and congenital hypertrophic pyloric stenosis. Fertility was slightly
      improved and the rate of twins increased significantly after periconceptional
      multivitamin supplementation. The effect of multivitamin supplementation for
      fetal death is controversial, but in general there is no clinically significant
      change. Periconceptional multivitamin supplementation can reduce the occurrence
      of nausea and vomiting. PRACTICAL IMPLEMENTATIONS: Consumption of foods which are
      rich in folate may not be the best way to prevent neural-tube defects and other
      congenital abnormalities. Periconceptional multivitamin supplementation is part
      of the periconceptional care in Hungary and it is an appropriate forum for the
      practical delivery for this primary prevention action. However, as a large
      proportion of pregnancies are unplanned, the widespread use of bread fortified
      with folic acid, vitamin B12 and B6 may decrease a considerable part of neural
      tube defects and some other congenital abnormalities, in addition to vascular
      diseases due to hyperhomocysteinemia.

PMID- 9622313
TI  - Preconceptional health care model.
AB  - During the last 10 years, there has been a movement to expand the definition of
      prenatal care to encompass preconceptional counseling. Major organizations
      throughout the world have endorsed preconceptional counseling as an integral
      component of care for all women contemplating pregnancy. This article will assist
      health care providers who interact with women of reproductive age to understand
      the potential benefits and limitations of preconceptional counseling and to
      develop an approach to that service relating to nutrition, infections, and
      metabolic diseases as they impact on reproductive outcome. Although there are
      many potential benefits of the preconception health care model, barriers to its
      implementation remain.

PMID- 9622314
TI  - From birth to conception. Open or closed.
AB  - In this valedictory address the research of the Nijmegen homocysteine team on
      birth defects and vascular disease is presented. Hyperhomocysteinemia was found
      in women with neural tube defect (NTD) offspring, other birth defects and
      vascular disease. Raised homocysteine levels in the blood plasma can be explained
      by lack of B-vitamins (folic acid), mutation of the 5,10
      methylenetetrahydrofolate reductase genes or both. Genetic mutations were found
      on the first chromosome (677 C-->T and 1298 A-C) and can explain up to 50% of the
      NTD protective effect of folic acid. The inborn error of methionine-homocysteine
      metabolism was also found in cases with recurrent early pregnancy loss, schisis,
      congenital heart defects and vascular problems like placental abruption, infarcts
      and fetal growth retardation. One of the most exciting medical findings of the
      last years is that folic acid can prevent NTD defects. This might also hold for
      other birth defects and vascular disease.

PMID- 9622315
TI  - Vascular reconstruction: are we ready for the challenge?

PMID- 9622316
TI  - Regional distribution of exercise-induced pulmonary haemorrhage: horses and
      antelopes.

PMID- 9622317
TI  - Copper status and skeletal development in horses: still a long way to go.

PMID- 9622318
TI  - Exercise-induced pulmonary haemorrhage (EIPH) in horses results from locomotory
      impact induced trauma--a novel, unifying concept.
AB  - Exercise-induced pulmonary haemorrhage (EIPH) in horses, although of major
      welfare and economic importance worldwide, is of uncertain cause. It is accepted
      that the dorsocaudal region of the lung is particularly prone to the condition,
      but present theories of causation cannot satisfactorily explain the mechanism or
      pattern of occurrence. We propose that EIPH results from locomotory impact
      induced trauma; the mechanism being similar to that producing lung tissue damage
      following thoracic impact injury. In impact injury, the localised impulsive load
      on the chest wall is transmitted by pressure waves through the lung at a slower
      speed than in the chest wall. The waves are subsequently reflected from the
      distal chest wall and other structures, producing a complex pattern of wave
      motion; waves travelling from regions of large cross-section to narrower ones are
      amplified in magnitude, consequently these regions can experience very high local
      stresses. Compression/dilation and shear waves are produced within the parenchyma
      and the latter particularly have been implicated as the cause of parenchymal
      damage and rupture with oedema and haemorrhage. This form of soft tissue damage
      has been shown to occur at remarkably low loads with an impact velocity greater
      than about 11 m/s and pressure exceeding approximately 14 kPa. In the horse, the
      lung is subjected to comparable levels of locomotory derived impulsive force
      during moderate to high speed exercise and this is the basis of the mechanism
      causing EIPH. During locomotion, the force following ground-strike of the front
      legs is transmitted, with some attenuation, through the forelimbs to the
      scapulae. The anatomical arrangement of the scapula, coupled with the direction
      of the force at the shoulder (scapulo humeral joint) produces an impulsive force
      on the rib cage, approximately just below mid height of the frontal aspect of the
      chest approximately over the fourth rib. As a result, pressure waves are
      transmitted through the lung parenchyma towards the dorsal and caudal regions;
      these waves are subsequently reflected at the distal chest wall, spine and
      diaphragm causing a complex pattern of wave interaction. The observed locations
      of EIPH are at the sites where wave intensity is expected to be greatest due to
      changes in cross section and reflection. Based on available information, it is
      estimated that impulsive forces of more than 100 kPa, lasting approximately 10
      ms, would be applied to the chest wall by each scapula in a 500 kg horse when
      galloping; this level of force would be sufficient to cause oedema and
      haemorrhage as observed in impact induced injury.

PMID- 9622319
TI  - Tapeworm infection is a significant risk factor for spasmodic colic and ileal
      impaction colic in the horse.
AB  - The association between the equine intestinal tapeworm Anoplocephala perfoliata
      and specific types of intestinal disease was investigated by matched case-control
      study using coprological and serological diagnosis. We have previously shown that
      the host IgG(T) response to 12/13 kDa antigens of A. perfoliata correlates well
      with infection intensity, therefore this antibody response was used to
      investigate the risk of colic at different levels of parasite infection
      intensity. One hundred and three spasmodic colic cases with an equal number of
      controls matched for age, breed and gender, and 20 ileal impaction cases each
      with 2 similarly matched controls were obtained. Cases of spasmodic colic were
      much more likely (odds ratio = 8.0) to be associated with A. perfoliata infection
      detected coprologically than controls. Serological diagnosis revealed an
      increasing risk of spasmodic colic with increasing infection intensity.
      Calculation of an aetiological fraction suggests that 22% of spasmodic colic
      cases in this study were tapeworm associated. No significant association was
      found between colic and strongyle egg count. Conditional logistic regression
      analysis demonstrated that the relationship between colic and A. perfoliata
      infection intensity was not confounded by strongyle egg count and there was a
      linear relationship between infection intensity and the log-odds of spasmodic
      colic. For cases of ileal impaction, a strong association was found between colic
      and A. perfoliata as diagnosed by coprological means (odds ratio of 34.0).
      Serological diagnosis also revealed a strong association that increased with
      higher levels of infection intensity (odds ratio = 26.0). The aetiological
      fraction for the ileal impaction data suggests that 81% of the ileal impaction
      cases in this study were tapeworm associated. This study concludes that A.
      perfoliata is a significant risk factor for spasmodic colic and ileal impaction
      colic in the horse; and that the risk of spasmodic colic increases with infection
      intensity.

PMID- 9622320
TI  - Effect of copper supplementation on copper status of pregnant mares and foals.
AB  - Pregnant Thoroughbred mares (n = 21) were grazed on tall fescue pasture
      containing 4.4-8.6 mg Cu/kg dry matter (DM). Twelve mares were supplemented with
      approximately 0.5 mg Cu/kg liveweight (LW)/day as copper sulphate for the final
      13-25 weeks gestation. Plasma copper concentration declined during the third
      trimester for all mares and was not affected by copper supplementation. Liver
      copper concentration of mares and foals was determined when the foals were 4-10
      days-old. Copper supplementation of the mares tended to increase mare liver
      copper concentration (P<0.08) and increased foal liver copper concentration
      (P<0.01). There was a significant relationship between mare and foal liver copper
      concentration (P<0.001, r2 = 0.7). Increasing the copper intake of mares is
      effective in enhancing the copper status of foals.

PMID- 9622321
TI  - Effect of copper supplementation on the copper status of pasture-fed young
      Thoroughbreds.
AB  - The effect of copper supplementation of pasture fed mares and foals on the copper
      status of the foals, in terms of plasma, soft tissue and bone copper
      concentrations and caeruloplasmin activity, was investigated. Twenty-one
      Thoroughbred foals from either control mares (n = 9), or copper-supplemented
      mares (n = 12) were divided randomly into control (pasture only, n = 10) or
      supplemented (pasture and oral copper sulphate, n = 11) groups. The pasture diet
      was grazed by all animals, and contained 4.4-8.6 mg Cu/kg dry matter (DM). The
      copper supplement for the mares contained copper sulphate equivalent to 0.5 mg
      Cu/kg liveweight (LW)/day. This daily dose was converted to allow administration
      as a thrice weekly dose (i.e. multiplied by 7/3) which was given for 13-25 weeks
      prior to foaling. The supplemented foals, also dosed 3 times a week, received 0.2
      mg Cu/kg LW/day at age 21 days, which was increased to 0.5 mg Cu/kg LW/day at 49
      days and was continued at this level until euthanasia at 150 days. Foal plasma
      copper concentration and caeruloplasmin activity increased from birth to 21 days
      post partum and then plateaued at a concentration similar to the mare, but the
      rise in these indices was not affected by copper supplementation of the mare or
      foal. Copper supplementation of the foal increased foal liver copper
      concentration at 150 days (P<0.03). Copper intake of diets containing
      approximately 8-28 mg Cu/kg DM is well reflected by liver copper concentration,
      but is poorly reflected by bone, other soft tissue copper concentrations and
      circulating copper status indices.

PMID- 9622322
TI  - Effect of copper supplementation on the evidence of developmental orthopaedic
      disease in pasture-fed New Zealand Thoroughbreds.
AB  - The effect of copper status on the evidence of bone and cartilage lesions was
      investigated in 21 Thoroughbred foals. The foals and their dams were grazed on
      pasture containing 4.4-8.6 mg Cu/kg dry matter (DM). Four treatment groups were
      created by randomly allocating mares and their foals to either copper
      supplemented (0.5 mg Cu/kg liveweight (LW)/day), or control (pasture only)
      groups. This experimental design allowed the effect of copper supplementation of
      mare and foal to be examined independently. Parameters of bone and cartilage
      development were assessed in the foals both in vivo, and at post mortem at
      approximately age 150 days. Mare copper supplementation significantly (P<0.01)
      decreased radiographic indices of physitis in the distal third metatarsal bone of
      the foals at 150 days, and the prevalence of articular cartilage lesions
      (P<0.05). Articular cartilage lesions were minor in all foals, with no evidence
      of clinical developmental orthopaedic disease (DOD) in vivo, with the exception
      of minor radiographic changes assessed at post mortem. Copper supplementation of
      the foal had no effect on any of the bone and cartilage parameters. Copper
      supplementation of the mares did not abolish DOD in the growing foals,
      emphasising the probable multifactorial nature of this condition. However, mare
      supplementation may be a useful treatment regime on a farm where the incidence
      and severity of DOD are of concern.

PMID- 9622323
TI  - Gross, histological and histomorphometric features of the navicular bone and
      related structures in the horse.
AB  - Forelimb navicular bones and associated soft tissues were collected from 3 groups
      of horses and subjected to pathological examinations. The groups consisted of 38
      horses with clinical navicular disease (ND) and 2 control groups, with no history
      of forelimb lameness, consisting of 25 age-matched mature horses (A-MC) and 9
      immature horses (IC). Histological and histomorphometric studies were performed
      on tissue samples from 10 ND, 10 A-MC and 5 IC horses. Gross changes seen only in
      ND horses included: full thickness defects in the palmar surface fibrocartilage,
      palmar cortex erosion, medullary lysis, flexor digitorum profundus tendon (FDPT)
      surface fibrillation, FDPT core lesions and adhesions between the FDPT and
      navicular bone. Palmar surface partial thickness fibrocartilage loss and distal
      border fragmentation were seen with a significantly greater incidence in ND than
      in A-MC and not observed in IC. Remodelling of the proximal border, FDPT surface
      colouration, palmar surface fibrocartilage colouration and proximal border
      entheseous bone were identified in ND and A-MC but not in IC. Mid-ridge synovial
      fossae and horizontal depressions in the palmar surface were identified in all
      groups. Histologically palmar fibrocartilage thinning and loss were associated
      with reduced palmar fibrocartilage cell density and chondrocyte cluster
      formation. Palmar fibrocartilage fibrillation, palmar cortical bone defects,
      fibromyxoid stromal change in the medulla, medullary pseudocyst formation and
      entheseous new bone formation were all seen in ND. The adjacent FDPT showed
      fibrillation, tag formation and degeneration of the dorsal surface. Necrotic foci
      were also present within the body of the tendon. Although not always present,
      medullary bone pseudocysts, separate mineralised foci and most changes on the
      dorsal surface of the FDPT were specific to ND. Bone histomorphometric parameters
      were compared among groups. Cross-sectional area reduced from the sagittal ridge
      to the medial and lateral margins of each navicular bone. IC navicular bones had
      a smaller subchondral area, subchondral bone volume and a greater osteoid volume
      than in the AC, indicating that these differences were age-related. In ND the
      medullary area was decreased but the trabecular bone volume increased. The palmar
      subchondral area was increased but contained bone with an increased porosity and
      osteoid volume. Changes occurred from the medial to the lateral margins of the
      bone in horses with ND indicating remodelling of the bony elements throughout the
      bone in ND. The histological and histomorphometric changes in the navicular bone
      and palmar fibrocartilage were considered similar of those found in articular
      hyaline cartilage and subchondral bone in osteoarthritis.

PMID- 9622324
TI  - Reconstruction of the jugular vein in horses with post thrombophlebitis stenosis
      using saphenous vein graft.
AB  - A surgical technique is described in which a saphenous vein graft is used to
      reconstruct the jugular vein in horses with facial oedema due to post
      thrombophlebitic stenosis of the jugular vein. The saphenous vein was harvested
      from the contralateral limb and implanted in the occluded vein by 2 side-to-end
      anastomoses. Intra- and post operatively anticoagulative medication was
      administered. In 2 out of 3 patients the reconstruction resulted in a permanent
      patent graft and resolution of the facial oedema. In one patient the graft
      thrombosed.

PMID- 9622325
TI  - Impact of mixed strongyle infections in foals after one month on pasture.
AB  - Twelve Standardbred foals (age 3-6 months), with little previous exposure to
      parasites, were allocated to 2 groups and put onto pasture with low (Group L) or
      high (Group H) levels of larval contamination of large strongyles and
      cyathostomes. After 4 weeks grazing in September, the foals were housed indoors
      until necropsy 15 weeks later. Foals in Group H became clinically more affected
      than those of Group L in that they showed loss of vigour, weight gain depression,
      intermittent soft faeces and inappetence. One foal of Group H had persistent
      diarrhoea and was subjected to euthanasia 12 weeks after housing. Signs of colic
      were not observed. Faecal egg counts were significantly higher in Group H than in
      Group L (P<0.05). At necropsy, the mean number of S. vulgaris and cyathostomes
      was 20 and 18,000, respectively, in Group L, and 167 and 25,000 in Group H.
      Routine blood chemistry did not specifically reveal presence of S.vulgaris in pre
      patency. A transient neutrophilia and eosinophilia, most prominent in Group H,
      was seen 2-8 weeks after start of exposure and anaemia was observed later in
      Group H. Serum albumin and albumin/globulin ratio were reduced, particularly in
      Group H, and a marked hyperbetaglobulinaemia was observed at 16-20 weeks in Group
      H. In conclusion, heavy infections with strongyles including S. vulgaris may
      become established in weaned foals after a brief period on pasture. Infections
      may be expressed clinically as debilitation, inappetence and intermittent
      diarrhoea without colic, and the need for control is imperative.

PMID- 9622326
TI  - Fluid administration attenuates the haemodynamic effect of frusemide in running
      horses.
AB  - The effect of blood volume repletion after frusemide administration on the right
      atrial and pulmonary artery pressure responses of horses to exercise has not been
      reported. We examined right atrial and pulmonary artery pressure and plasma
      atrial natriuretic peptide concentration (ANP) responses to an incremental
      exercise test in 6 Standardbred mares. Horses were treated, in a 3 way cross over
      design, with isotonic saline, frusemide (1 mg/kg bwt, i.v.), and frusemide
      followed 3 h later by lactated Ringer's solution (12 ml/kg bwt, i.v.). Three and
      a half hours after saline or frusemide administration the horses completed a
      standard exercise test. Frusemide significantly affected the right atrial and
      pulmonary artery pressure and ANP responses to exercise. Fluid administration
      decreased plasma total protein concentrations at rest and during running and
      abolished the effects of frusemide on the haemodynamic and ANP responses to
      exercise. These results suggest that the haemodynamic effect of frusemide in
      running horses is mediated, in large part, by a reduction in plasma and blood
      volume.

PMID- 9622327
TI  - Electromyographic activity of the long digital extensor muscle in the exercising
      Thoroughbred horse.
AB  - Surface electrodes were used to record electromyographic (EMG) activity of the
      long digital extensor muscle on the right hindlimb of 8 Thoroughbred horses for 8
      s at the walk and 8 s at the trot before (unfatigued) and after (fatigued) an
      exercise test. The exercise test was performed on a motorised treadmill set on a
      10% grade. Each test started at a speed of 6 m/s which was increased by 1 m/s
      each minute until the horse fatigued as indicated by its inability to keep pace
      with the treadmill with minimal encouragement. Observations were made on the
      horses prior to conditioning (untrained state) and after 8 weeks of regular
      exercise (trained state). The mean root-mean-square (rms) values of EMG bursts
      collected in each experimental trial were determined for each horse and group
      means were derived from the mean of independent subjects. Statistical comparisons
      for differences in rmsEMG were related to gait, fatigue and training. Mean rmsEMG
      at the trot was consistently higher than at the walk (P<0.05). At the walk, mean
      fatigued rmsEMG tended to be higher than the mean unfatigued rmsEMG in the
      untrained state and was significantly higher in the trained state (P<0.05). At
      the trot, mean fatigued rmsEMG was higher (P<0.05) than mean unfatigued rmsEMG in
      both the untrained and trained states. Training did not have an effect on mean
      rmsEMG of unfatigued muscles at the walk or the trot (P>0.05). However, fatigued
      muscles experienced higher EMG activity in the trained state at the walk
      (P<0.05). A similar tendency was observed at the trot. Results of this study
      suggest that surface EMG measurement may be useful for evaluating fatigue in
      exercising horses.

PMID- 9622328
TI  - Quantitative assessment of motor neuron loss in equine motor neuron disease
      (EMND).
AB  - The mean number of motor neurons was assessed in the C7 spinal cord segment of 5
      EMND and 5 control horses. Mean number per section in EMND horses was reduced
      significantly (P<0.001). The mean neuronal loss was estimated at 31%. Each of the
      5 affected horses had a mean neuronal count below the 95% confidence interval for
      control horses. The statistically significant difference between the 2 groups was
      consistent in the cranial, middle and caudal thirds of the C7 segment (P<0.001).
      The results of regression analysis indicated an association between neuronal
      reduction in EMND horses and the duration of the disease when adjusted for age
      (P<0.001). This is the first quantitation of the neurodegenerative loss in EMND
      and it provides a clearer explanation for residual deficits in horses that
      survive EMND.

PMID- 9622329
TI  - Ex vivo simulation of in vivo strain distributions in the equine metacarpus.
AB  - The objective of this study was to examine several simple ex vivo loading
      conditions for the equine metacarpus, and to evaluate their ability to reproduce
      the mid-diaphyseal bone surface strain distributions previously reported in vivo
      at the walk and trot. Distributed axial compressive loads, and 9 different axial
      compressive point loads at -7.5 kN and -15 kN were applied to metacarpal-distal
      carpal bone preparations from 6 Thoroughbred horses, aged 1-5 years. The
      resulting dorsal, medial, palmar, and lateral mid-diaphyseal bone surface axial
      and shear strains were compared with previously reported in vivo surface strain
      distributions using a root mean square error (RMSE) protocol. The effects of
      loading condition and load magnitude on RMSE were assessed with a mixed-model
      analysis of variance. There were significant differences between loading
      conditions, and, in most cases, between load magnitudes, in the fit of the ex
      vivo to the in vivo strain distributions. In vivo mid-diaphyseal bone surface
      strain distributions at the walk can be well approximated ex vivo by a
      distributed axial compressive load, or by a point load positioned 0.5 cm medial
      to the sagittal midline, at -7.5 kN loads. In vivo mid-diaphyseal bone surface
      strain distributions at the trot can be well approximated by the -15 kN loads
      applied to the same locations. These simplified loading conditions can be used in
      designing biologically relevant loading protocols for ex vivo mechanical testing
      studies, as well as in developing boundary conditions for finite element
      analysis. As such, these loading conditions may be considered as tools to be used
      as a means of replicating in vivo loading conditions during the initial design
      and testing stages in the development of fracture fixation devices, as well as in
      the theoretical mechanical analysis of the metacarpal structure.

PMID- 9622330
TI  - Field case study of equine rhinovirus 1 infection: clinical signs and
      clinicopathology.

PMID- 9622331
TI  - Epiglottic retroversion as a cause of upper airway obstruction in two horses.

PMID- 9622332
TI  - Other men's (and women's) flowers.

PMID- 9622333
TI  - Excess energy intake and low energy expenditure as predictors of obesity.

PMID- 9622334
TI  - Energy intake in early infancy and childhood fatness.
AB  - OBJECTIVE: To investigate whether aspects of infant energy intake are related to
      fatness in early childhood. DESIGN: Longitudinal investigation of infants studied
      at 12 weeks and 2-3.5 y. SUBJECTS: 20 healthy infants, breast-fed or formula-fed,
      from the general population. MEASUREMENTS: Milk volume intake (MVI) by deuterium
      turnover, estimated energy intake, weaning status and body composition in
      infancy, body composition in childhood. RESULTS: MVI was not related to infant
      skinfolds or percentage fat. Weaning was inversely related to MVI (P < 0.04) at
      12 weeks, and inversely related to skinfolds (P = 0.055) and fat mass (P = 0.020)
      in childhood. MVI and total energy intake were not related to childhood fatness.
      CONCLUSIONS: Early weaning was associated with a moderate reduction in childhood
      fatness. Two possible mechanisms are discussed. However, early infant energy
      intake was not an important determinant of later fatness in this population.

PMID- 9622335
TI  - Psychological functioning of morbidly obese patients after surgical treatment.
AB  - OBJECTIVE: To investigate the long-term effects of surgically induced weight loss
      on the psychological functioning of morbidly obese patients. DESIGN: Comparison
      between preoperative and postoperative psychometric test results in a cross
      sectional study. PATIENTS AND METHODS: Three psychometric tests were administered
      to 62 morbidly obese patients before and after surgery. RESULTS: The mean follow
      up was 85.9+/-48.1 months. Surgical treatment resulted in a mean weight loss of
      45.0+/-21.3 kg (P < 0.0001). The psychometric test results before surgery
      demonstrated somatisation, depression, denial of emotional stress, social
      incompetence and an indifferent attitude towards certain aspects of interpersonal
      behaviour. All psychopathology, except for somatisation, disappeared after
      surgical treatment. Improvement of psychological functioning was determined by
      weight loss and not influenced by the surgical procedure. The level of self
      esteem before surgery predicted 15.4% of the outcome variance (P < 0.05).
      CONCLUSION: The psychopathology before surgery is almost totally reversed after
      sustained, surgically induced weight loss. This suggests that the preoperative
      psychological disturbances are the result, rather than the cause, of morbid
      obesity.

PMID- 9622336
TI  - Urinary albumin excretion and heart rate variability in obese women.
AB  - OBJECTIVE: The aim of this work was to examine the relationship between cardiac
      autonomic function and urinary albumin excretion in obesity. SUBJECTS: These were
      27 obese non-diabetic postmenopausal women and 18 non-obese healthy
      postmenopausal women. MEASUREMENTS: Urinary albumin excretion as well as plasma
      nitrate, both indices of capillary function, were measured. Power spectral
      analysis of heart rate variability was performed, as a measurement of vagal
      function. An oral glucose tolerance test (OGTT) was performed and blood lipids
      were analysed. RESULTS: The obese women were characterized by higher fasting
      insulin, sum of glucose, triglycerides and lower high density lipoprotein
      cholesterol (HDL), the latter of borderline significance, than controls. Urinary
      albumin excretion (UAE), plasma nitrate and heart rate variability were not
      different between obese and control women. However, in obese women log UAE
      correlated positively with systolic and diastolic blood pressure, and inversely
      with heart rate variability, the latter independent of body mass index (BMI) and
      the waist/hip circumference ratio. CONCLUSION: It was concluded that this inverse
      association between UAE and parasympathetic activity in obese women may be an
      early sign of derangements of endothelial function and autonomic nervous system
      control, which may contribute to the increased risk of cardiovascular mortality
      in abdominal obesity.

PMID- 9622337
TI  - Obesity related phenotypes in families selected for extreme obesity and leanness.
AB  - BACKGROUND: Obesity is a multigenic trait, and special methods and sampling
      designs are needed for gene identification. OBJECTIVE: To describe
      characteristics of families selected to increase information for genetic linkage
      studies of obesity. DESIGN: Families having extremely obese siblings with a lean
      parent and sibling. SUBJECTS: 594 members of 94 Caucasian families. MEASUREMENTS:
      Measured height and weight, bioelectric impedance, skinfolds, circumferences and
      questionnaires. RESULTS: Families have an extreme range of obesity phenotypes,
      which are bimodally distributed. The obese individuals are predominantly women
      with an onset of obesity early in life. Obesity onset age was negatively
      correlated with level of obesity, and onset ages were correlated among family
      members. Individual obesity measures were highly correlated. The extreme range of
      phenotypes within families increases family variability and presumably gene
      segregation. CONCLUSION: Sampling families through extremely obese sibling pairs
      with a lean parent and sibling results in families with an extreme range of
      obesity and leanness. The large within-family variance and early age of onset
      should make these families highly informative for gene mapping and gene
      identification studies.

PMID- 9622339
TI  - Changes in diet and physical activity affect the body mass index of Chinese
      adults.
AB  - OBJECTIVE: To examine the relationship between diet, particularly dietary fat
      intake, and body mass index (BMI). DESIGN: Prospective study of adults who
      participated in the 1989 and 1991 China Health and Nutrition Survey. SUBJECTS:
      3484 adults aged 20-45 at baseline (1989) survey. MEASUREMENTS: Measurement of
      dietary intake with replicated 24 h dietary recalls. Anthropometric measurements.
      Measurements of physical activity, smoking habit and socio-economic factors.
      RESULTS: Change in fat intake was positively associated with change in BMI in men
      (beta=0.00036, P=0.0001), and change in physical activity level was inversely
      associated with change in BMI in women (beta=-0.12, P=0.02). Energy intake,
      physical activity and major socio-economic factors were related to BMI in cross
      sectional analysis. CONCLUSIONS: Diet is becoming an increasingly important
      determinant of body weight in this population, where fat and energy consumption
      has been increasing steadily during the past decade.

PMID- 9622338
TI  - Hepatic secretion of very-low-density lipoprotein apolipoprotein B-100 studied
      with a stable isotope technique in men with visceral obesity.
AB  - OBJECTIVE: To test the hypothesis that the hepatic secretion of very-low-density
      lipoprotein (VLDL) apolipoprotein B-100 (apoB) is increased in men with visceral
      obesity and to examine whether the oversecretion of this apolipoprotein is
      related to insulin resistance and increased hepatic availability of lipid
      substrates. SUBJECTS: 16 obese men (body mass index (BMI) > 30 kg/m2, waist
      circumference > 100 cm) and 16 non-obese, age matched men, were studied.
      MEASUREMENTS: The hepatic secretion of VLDL apoB was measured using a primed (1
      mg/kg), constant (1 mg/kg/h), intravenous infusion of 1-[13C]-leucine. Isotopic
      enrichment of VLDL apoB was determined using gas-chromatography mass spectrometry
      and a multi-compartmental model (SAAM-II) was used to estimate the fractional
      turnover rate of VLDL apoB. RESULTS: Plasma concentrations of total cholesterol,
      triglyceride, glucose, insulin, mevalonic acid and lathosterol, as well as
      dietary fat intake, were significantly higher (P < 0.05) in obese than control
      subjects. The obese subjects had significantly lower high-density-lipoprotein
      cholesterol (P < 0.01). VLDL apoB pool size and hepatic secretion rate (mg/kg fat
      free mass/d) were significantly higher in the obese than non-obese subjects (P <
      0.02). The fractional catabolic rate of VLDL apoB was lower in the obese subjects
      compared with controls, but the difference did not attain conventional
      significance (P=0.053). In pooled analysis, there was a significant positive
      association (P < 0.05) between VLDL apoB secretion rate (mg/kg fat free mass/d)
      and waist-to-hip ratio (WHR), waist circumference, and fasting plasma
      triglyceride, insulin and glucose concentrations. In multiple linear regression
      analysis, the association between VLDL apoB secretion and fasting insulin
      concentration was independent of age, apolipoprotein E (apoE) genotype, mevalonic
      acid concentration, free fatty acid concentration and fat intake. CONCLUSION: Our
      findings are consistent with the hypothesis that in visceral obesity, insulin
      resistance and the associated increased lipid substrate supply to the liver
      contribute to hepatic oversecretion of apoB; expansion in the VLDL apoB pool size
      may also be due to a catabolic defect related to insulin resistance.

PMID- 9622340
TI  - Associations of indices of adiposity with atherogenic lipoprotein subfractions.
AB  - OBJECTIVE: To investigate the associations of indices of adiposity with
      cardiovascular risk factors. SUBJECTS: 93 men and 98 women aged 18-69 y. OUTCOME
      MEASURES: Body mass index (BMI), waist to hip ratio (WHR), waist circumference,
      waist to height ratio, blood pressure, fasting concentrations of blood glucose,
      insulin, plasma lipids and lipoprotein subfractions, apoproteins, lipoprotein(a)
      and post-heparin lipases. RESULTS: BMI and waist showed similar associations (P <
      0.01) with a cluster of major cardiovascular risk factors including total
      cholesterol, low density lipoprotein-cholesterol and very low density lipoprotein
      cholesterol in men, and ratio of low density lipoprotein-/high density
      lipoprotein-cholesterol for both genders. Large waist circumference was
      significantly (P < 0.01) associated (controlled for age and smoking) with
      features of the metabolic syndrome, including raised insulin concentration (men:
      r=0.37, women: r=0.49), reduced high density lipoprotein2 (men: r=-0.30, women:
      r=-0.34), increased very low density lipoprotein1 mass (men: r=0.31, women:
      r=0.42), raised small, dense low density lipoprotein (men: r=0.30, women:
      r=0.31), elevated blood pressure (men: r=0.27, women: r=0.28), increased
      triglyceride (men: r=0.43, women: r=0.48) and apolipoprotein-B (men: r=0.32,
      women: r=0.35). Waist circumference also correlated with hepatic
      lipase/lipoprotein lipase ratio in women (r=0.52). Height adjustment did not
      substantially change relationships between waist circumference and risk factors.
      WHR correlated with fewer risk factors. CONCLUSION: For the purpose of health
      promotion to prevent cardiovascular disease associated with overweight and intra
      abdominal fat accumulation, the general public should be advised to be aware of
      the risk associated with large waist circumference.

PMID- 9622341
TI  - Energy expenditure and physical fitness in overweight vs non-overweight
      prepubertal girls.
AB  - OBJECTIVE: To determine whether overweight children have lower physical activity
      energy expenditure (EE) and fitness levels than non-overweight children. STUDY
      DESIGN: Twenty-four healthy girls aged 7-10 y were divided into overweight (>
      95th percentile weight-for-height) and non-overweight (10-90th percentile)
      groups. Basal metabolic rate (BMR), sleeping metabolic rate (SMR), 24 h sedentary
      EE (SEE) and total EE (TEE) were measured by room respiration calorimetry and
      doubly labelled water. Physical activity EE and physical activity level (PAL)
      were calculated. Fitness (VO2peak) was measured by a treadmill exercise test.
      RESULTS: The overweight group had significantly higher body weight, percent fat,
      fat mass and fat-free mass (FFM) (P < 0.001). The overweight girls had higher
      BMR, SMR, SEE and TEE (P < 0.001), but not after adjustment for FFM. Physical
      activity EE and PAL were not significantly different between groups. After
      adjusting for FFM or weight, submaximal and peak VO2 were not significantly
      different between groups. CONCLUSIONS: We conclude that these overweight girls do
      not have lower physical activity EE or fitness levels than the non-overweight
      prepubertal girls, however, the rather high body fat of the non-overweight group
      may have precluded us from finding any differences between groups.

PMID- 9622342
TI  - Development of insulin-responsive glucose uptake and GLUT4 expression in
      differentiating human adipocyte precursor cells.
AB  - OBJECTIVE: In differentiating human preadipocytes glucose uptake in the presence
      of insulin is a prerequisite for lipid accumulation. The aim of this study was to
      characterize the insulin-regulated glucose transport system during and after
      differentiation. DESIGN AND METHODS: Human adipocyte precursor cells kept in
      primary culture were allowed to differentiate into fat cells under serum-free
      hormone-supplemented conditions. 2-Deoxy-glucose uptake was measured as a
      functional parameter of the glucose transport system, the amount of GLUT1 and
      GLUT4 protein was determined by Western blotting. RESULTS: In the
      undifferentiated state, cells did not increase 2-deoxy-glucose uptake in response
      to insulin. On day 16, when cells have acquired the adipocyte phenotype, there
      was a 3-4-fold stimulation of glucose transport by insulin compared to basal
      rates, whereas basal glucose uptake was dramatically diminished. Measurement of
      GLUT4 protein in cell extracts, showed a marked increase in the amount of this
      insulin-regulated transporter isoform during the differentiation period. On
      average, the amount of GLUT4 was 16.7-fold greater after than before
      differentiation. In contrast, the amount of GLUT1 protein decreased during
      differentiation to almost undetectable levels on day 16. When newly developed
      adipocytes were maintained in culture for another 14d, the stimulation of glucose
      uptake and the amount of GLUT4 remained stable. CONCLUSION: Differentiating human
      fat cells in primary culture develops an insulin-responsive glucose transport
      system which exhibits a high stability, thereby providing a valuable model for
      long-term studies of glucose transport and GLUT4 expression in human adipocytes.

PMID- 9622343
TI  - Low body mass index in non-meat eaters: the possible roles of animal fat, dietary
      fibre and alcohol.
AB  - OBJECTIVE: To examine the associations of diet and other lifestyle factors with
      body mass index (BMI) using data from the Oxford Vegetarian Study. SUBJECTS: 1914
      male and 3378 female non-smokers aged 20-89 y at recruitment to the study.
      MEASUREMENTS: All subjects completed a diet/lifestyle questionnaire at
      recruitment giving details of their usual diet and other characteristics
      including height and weight, smoking and drinking habits, amount of exercise,
      occupation and reproductive history. Answers to the food frequency questionnaire
      were used to classify subjects as either meat eaters or non-meat eaters, and to
      estimate intakes of animal fat and dietary fibre. Subjects were further
      classified according to their alcohol consumption, exercise level, social class,
      past smoking habits and parity. RESULTS: Mean BMI was lower in non-meat eaters
      than in meat eaters in all age groups for both men and women. Overall age
      adjusted mean BMIs in kg/m2 were 23.18 and 22.05 for male meat eaters and non
      meat eaters respectively (P < 0.0001) and 22.32 and 21.32 for female meat eaters
      and non-meat eaters respectively (P < 0.0001). In addition to meat consumption,
      dietary fibre intake, animal fat intake, social class and past smoking were all
      independently associated with BMI in both men and women; alcohol consumption was
      independently associated with BMI in men, and parity was independently associated
      with BMI in women. After adjusting for these factors, the differences in mean BMI
      between meat eaters and non-meat eaters were reduced by 36% in men and 31% in
      women. CONCLUSIONS: Non-meat eaters are thinner than meat eaters. This may be
      partly due to a higher intake of dietary fibre, a lower intake of animal fat, and
      only in men a lower intake of alcohol.

PMID- 9622344
TI  - Body mass index and percentage fat mass in healthy German schoolchildren and
      adolescents.
AB  - OBJECTIVE: To provide reference data for obesity indices in Mid-European
      schoolchildren and adolescents, to evaluate the usefulness of body mass index
      (BMI) as an indicator of obesity in children, and to analyse the patterns of fat
      accumulation during childhood. DESIGN: Cross-sectional observational study in
      2554 healthy schoolchildren and adolescents (age, 6-19 y) living in Heidelberg,
      Germany in 1989/1990. Centile charts for BMI and skinfold-derived percentage body
      fat mass (PFM) were constructed using Cole's LMS method for normalised growth
      standards. RESULTS: The BMI centile values of German children ranged higher than
      French, lower than North American and Italian, and similar to Swedish and British
      children. While BMI steadily increased with age, PFM was markedly lower in
      peripubertal than in pre- and postpubertal boys. BMI predicted PFM with
      reasonable precision in girls (r=0.84), and in obese boys (r=0.58), but not in
      the leaner two thirds of the male population (r=0.01, NS). The 75th BMI
      percentile was the most appropriate cutoff value to screen for the 15% most obese
      patients by PFM (sensitivity: 82%, specificity: 85%). The pattern of the trunk-to
      extremity skinfold ratio across childhood suggested that the typical adult
      distribution of central and peripheral fat is achieved in mid puberty in girls,
      but not before the end of adolescence in boys. CONCLUSIONS: The major differences
      observed between BMI charts obtained in different countries underline the need
      for population-specific reference data. BMI is of limited usefulness in
      predicting relative fat mass in individual children. The developmental pattern of
      fat accumulation and distribution during adolescence is highly dynamic and gender
      specific.

PMID- 9622345
TI  - Eating habits, activity, lipids and body mass index in Japanese children: the
      Shiratori Children Study.
AB  - OBJECTIVE: To describe the eating habits and physical activity of Japanese
      children aged 10 y, and to investigate their relationship to lipids and body mass
      index (BMI); also to study the relationship between BMI and lipids in these
      children. DESIGN: This was a cross-sectional study conducted at six schools in
      Shiratori, Japan during 1992-1994. Physical examinations and questionnaires were
      used to collect data from 457 fifth grade children, aged 10 y. RESULTS: The diet
      of these children was mixed, with Japanese and Western foods almost equally
      reported. Boys were more active than girls. More active children had higher high
      density lipoprotein cholesterol (HDL-C), and children who ate a more Japanese
      diet had slightly lower HDL-C. BMI was positively related to cholesterol, low
      density lipoprotein cholesterol (LDL-C), triglycerides and inversely related to
      HDL-C. The amount of rice intake was positively associated with the BMI of these
      children. CONCLUSION: In our study of Japanese children aged 10 y, their diets
      were fairly Westernized, and most children were fairly inactive based on our
      activity score. Although obesity is low in these young Japanese subjects (14.1%),
      children who were obese (BMI>20) had worse lipid profiles than those who were not
      obese. An exceptionally high rice intake was associated with obesity, and thus
      may be an early warning sign for future obesity.

PMID- 9622346
TI  - The impairment of flow-mediated vasodilatation in obese men with visceral fat
      accumulation.
AB  - BACKGROUND: Obesity has been reported to be associated with coronary artery
      disease and other atherosclerotic diseases. Recently, evidence has accumulated
      indicating that intra-abdominal visceral fat accumulation contributes to
      atherogenesis; however, the mechanism underlying this remains to be determined.
      This study was undertaken to elucidate whether intra-abdominal visceral fat
      accumulation impairs vascular endothelial function in obese men. METHODS AND
      RESULTS: Thirty-eight obese men (body mass index (BMI) > or = 26.0), aged 19-64 y
      (mean age 37.6 +/- 1.8 y) and 23 age-matched non-obese subjects were examined.
      According to the ratio of the maximum thickness of preperitoneal fat to the
      minimum thickness of subcutaneous fat (Pmax/Smin) obtained by longitudinal
      ultrasound scanning in the subxiphoid region in obese men, we divided obese
      subjects into two categories; visceral (Pmax/Smin > or = 1; n=23) and
      subcutaneous type (Pmax/Smin < 1; n=15). To investigate endothelial function, we
      performed ultrasound measurement of the brachial artery diameter non-invasively
      both at rest and during reactive hyperaemia in the muscle distal to the brachial
      artery which causes endothelium-dependent vasodilatation. The brachial diameter
      change was also measured after sublingual administration of nitroglycerin, which
      causes endothelium-independent vasodilatation. Flow-mediated diameter (D)
      increase (%FMD; deltaD/D x 100), in the subjects with visceral type obesity (3.09
      +/- 0.43%) was significantly lower than those of the subjects with subcutaneous
      type obesity and non-obese subjects (7.90 +/- 0.51%, 8.91 +/- 0.44%,
      respectively, P < 0.01). The magnitude of endothelium-independent vasodilatation
      by nitroglycerin was similar in all groups. On multiple regression analysis, the
      Pmax/Smin showed a significant inverse correlation with %FMD. CONCLUSIONS: The
      subjects with visceral type obesity, rather than those with the subcutaneous
      type, are associated with impaired flow-mediated endothelium-dependent
      vasodilatation of the brachial artery.

PMID- 9622347
TI  - The pursuit of thinness: a study of Dublin schoolgirls aged 15 y.
AB  - Despite increasing trends in the prevalence of overweight and obesity, fatness
      phobia is common during female adolescence. This study has demonstrated a high
      level of dissatisfaction with body weight in a sample of Dublin schoolgirls aged
      15 y. Of 420 subjects, 59% reported that they wanted to be slimmer and 68% had
      previously tried to lose weight. Contrary to expectations, overweight girls were
      not found to hold the monopoly on such dissatisfactions. Normal weight and even
      underweight girls also expressed a desire to be thinner and reported using
      unhealthy weight control practices including random avoidance of staple foods,
      fasting, smoking and purging, in their pursuit of the 'perfect' female figure.
      Obesity prevention programmes which target adolescent girls 'at risk' of
      overweight and obesity, must take cognizance of their profound fear of fatness,
      otherwise the use of harmful slimming strategies may be further increased as
      teenage girls frantically try to lose weight and to avoid the stigma associated
      with female fatness.

PMID- 9622348
TI  - Microbial magnesium transport: unusual transporters searching for identity.
AB  - Mg2+ is unique among biological cations because of its charge density and
      solution chemistry. This is abundantly reflected in its transport systems,
      studied primarily in Salmonella typhimurium. The constitutively expressed CorA
      transport system is the primary Mg2+ influx pathway for the Bacteria and the
      Archaea. Its structure of a large N-terminal soluble periplasmic domain with
      three transmembrane segments at the C-terminus is unique among membrane carriers,
      and its protein sequence bears no resemblance to other known proteins. The MgtE
      transport system can also mediate Mg2+ uptake, but whether this is its primary
      function is not known. MgtE also lacks homology to other known proteins. In
      contrast, the MgtA and MgtB Mg2+ transport systems of enteric bacteria are P-type
      ATPases by sequence homology, mediating Mg2+ influx with, rather than against,
      the Mg2+ electrochemical gradient. They are closely related to mammalian Ca2+
      ATPases. Expression of MgtA and MgtB is under the control of the PhoPQ two
      component regulatory system, important in bacterial virulence. In S. typhimurium,
      MgtB is encoded by a two-gene operon mgtCB; the function of the MgtC protein is
      unknown, and it lacks close homologues. The ligand for the PhoQ membrane sensor
      kinase is Mg2+ and, at decreased extracellular Mg2+ concentrations, transcription
      of mgtA and mgtCB are enormously induced. All three genes are also induced upon
      S. typhimurium invasion of epithelial or macrophage cells. Mutation of these
      genes has no effect on invasion efficiency, but an insertion in mgtC renders S.
      typhimurium essentially avirulent in the mouse. The physiological roles of the
      known Mg2+ transport systems are not yet completely defined. Nonetheless, the
      singular sequence and apparent structure of the CorA and MgtE transport proteins,
      the complex regulation of MgtA, MgtB and MgtC and their involvement in
      pathogenesis suggests that further study will be rewarding.

PMID- 9622349
TI  - Immunity proteins and their specificity for endonuclease colicins: telling right
      from wrong in protein-protein recognition.
AB  - Immunity proteins inhibit colicins, protein toxins released by bacteria during
      times of environmental stress, by binding and inactivating their cytotoxic
      domains. This protects the producing organism as it attempts to kill off
      competing bacteria. The cytotoxic domains of related colicins share a high degree
      of sequence identity, as do their corresponding immunity proteins, yet
      specificity and affinity are also high, with little non-cognate biological cross
      protection evident under physiological conditions. We review recent work on DNase
      specific immunity proteins, which shows that, although both cognate and non
      cognate proteins can bind a single toxin, their affinities can differ by as much
      as 12 orders of magnitude. We have termed this mode of binding dual recognition,
      because the DNase-binding surface of an immunity protein is made up of two
      components, one conserved and the other variable. The strength of the binding
      interaction is dominated by the conserved residues, while neighbouring variable
      residues control specificity. Similar dual recognition systems may exist in other
      biological contexts, particularly where a protein must discriminate the right
      binding partner from numerous, structurally homologous alternatives.

PMID- 9622350
TI  - Control of cell shape and elongation by the rodA gene in Bacillus subtilis.
AB  - The Escherichia coli rodA and ftsW genes and the spoVE gene of Bacillus subtilis
      encode membrane proteins that control peptidoglycan synthesis during cellular
      elongation, division and sporulation respectively. While rodA and ftsW are
      essential genes in E. coli, the B. subtilis spoVE gene is dispensable for growth
      and is only required for the synthesis of the spore cortex peptidoglycan. In this
      work, we report on the characterization of a B. subtilis gene, designated rodA,
      encoding a homologue of E. coli RodA. We found that the growth of a B. subtilis
      strain carrying a fusion of rodA to the IPTG-inducible Pspac promoter is inducer
      dependent. Limiting concentrations of inducer caused the formation of spherical
      cells, which eventually lysed. An increase in the level of IPTG induced a sphere
      to-short rod transition that re-established viability. Higher levels of inducer
      restored normal cell length. Staining of the septal or polar cap peptidoglycan by
      a fluorescent lectin was unaffected during growth of the mutant under restrictive
      conditions. Our results suggest that rodA functions in maintaining the rod shape
      of the cell and that this function is essential for viability. In addition, RodA
      has an irreplaceable role in the extension of the lateral walls of the cell.
      Electron microscopy observations support these conclusions. The ultrastructural
      analysis further suggests that the growth arrest that accompanies loss of the rod
      shape is caused by the cell's inability to construct a division septum capable of
      spanning the enlarged cell. RodA is similar over its entire length to members of
      a large protein family (SEDS, for shape, elongation, division and sporulation).
      Members of the SEDS family are probably present in all eubacteria that synthesize
      peptidoglycan as part of their cell envelope.

PMID- 9622351
TI  - Multicellular and aggregative behaviour of Salmonella typhimurium strains is
      controlled by mutations in the agfD promoter.
AB  - A colony morphology type is described in which cells of Salmonella typhimurium
      form a rigid multicellular network with expression of thin aggregative fimbriae
      that mediate tight intercellular bonds. Surface translocation of cells on plates
      and adherence to glass and polystyrene surfaces in biofilm assays are further
      characteristics of the morphotype. This morphotype (rdar) is normally expressed
      only at low temperature. However, in two unrelated S. typhimurium strains,
      spontaneous mutants were found forming rdar colonies independent of temperature.
      Allelic replacement proved a single point mutation in the promoter region of
      PagfD in each of the two mutants to be responsible for the constitutive phenotype
      of a multicellular behaviour. Transcription levels of the two divergently
      transcribed agf operons required for biogenesis of thin aggregative fimbriae by
      Northern blot analysis with gene probes for agfA and agfD as well as expression
      levels of AgfA by Western blotting were compared in the wild type, the
      constitutive mutants and their respective ompR and rpoS- derivatives. In the wild
      type the rdar morphotype and expression of thin aggregative fimbriae are
      restricted to low temperature on plates containing rich medium of low osmolarity,
      but biogenesis of thin aggregative fimbriae occurs upon iron starvation at 37
      degrees C. In the upregulated mutants biogenesis of thin aggregative fimbriae is
      only abolished at high osmolarity at 37 degrees C and in the exponential phase in
      broth culture. Control of expression of thin aggregative fimbriae and rdar
      morphology takes place at the transcriptional level at the agfD promoter. A
      functional ompR allele is required, however an rpoS mutation abolishes
      transcription only in the wild type, but has no influence on expression of thin
      aggregative fimbriae in the constitutive mutants.

PMID- 9622352
TI  - BipA: a tyrosine-phosphorylated GTPase that mediates interactions between
      enteropathogenic Escherichia coli (EPEC) and epithelial cells.
AB  - We report the functional characterization of BipA, a GTPase that undergoes
      tyrosine phosphorylation in an enteropathogenic Escherichia coli (EPEC) strain.
      BipA mutants adhere to cultured epithelial cells but fail to trigger the
      characteristic cytoskeletal rearrangements found in cells infected with wild-type
      EPEC. In contrast, increased expression of BipA enhances actin remodelling and
      results in the hyperformation of pseudopods. BipA appears to be the first example
      of a new class of virulence regulator, as it also controls flagella-mediated cell
      motility and resistance to the antibacterial effects of a human host defence
      protein. Its striking sequence similarity to ribosome-binding elongation factors
      suggests that it uses a novel mechanism to modulate gene expression.

PMID- 9622353
TI  - Specific RecA amino acid changes affect RecA-UmuD'C interaction.
AB  - The UmuD'C mutagenesis complex accumulates slowly and parsimoniously after a 12
      Jm(-2) UV flash to attain after 45 min a low cell concentration between 15 and 60
      complexes. Meanwhile, RecA monomers go up to 72,000 monomers. By contrast, when
      the UmuD'C complex is constitutively produced at a high concentration, it
      inhibits recombinational repair and then markedly reduces bacterial survival from
      DNA damage. We have isolated novel recA mutations that enable RecA to resist
      UmuD'C recombination inhibition. The mutations, named recA [UmuR], are located on
      the RecA three-dimensional structure at three sites: (i) the RecA monomer tail
      domain (four amino acid changes); (ii) the RecA monomer head domain (one amino
      acid change, which appears to interface with the amino acids in the tail domain);
      and (iii) in the core of a RecA monomer (one amino acid change). RecA [UmuR]
      proteins make recombination more efficient in the presence of UmuD'C while SOS
      mutagenesis is inhibited. The UmuR amino acid changes are located at a head-tail
      joint between RecA monomers and some are free to possibly interact with UmuD'C at
      the tip of a RecA polymer. These two RecA structures may constitute possible
      sites to which the UmuD'C complex might bind, hampering homologous recombination
      and favouring SOS mutagenesis.

PMID- 9622354
TI  - Antagonistic effects of dual PTS-catalysed phosphorylation on the Bacillus
      subtilis transcriptional activator LevR.
AB  - LevR, which controls the expression of the levoperon of Bacillus subtilis, is a
      regulatory protein containing an N-terminal domain similar to the NifA/NtrC
      transcriptional activator family and a C-terminal domain similar to the
      regulatory part of bacterial anti-terminators, such as BgIG and LicT. Here, we
      demonstrate that the activity of LevR is regulated by two phosphoenolpyruvate
      (PEP)-dependent phosphorylation reactions catalysed by the phosphotransferase
      system (PTS), a transport system for sugars, polyols and other sugar derivatives.
      The two general components of the PTS, enzyme I and HPr, and the two soluble,
      sugar-specific proteins of the lev-PTS, LevD and LevE, form a signal transduction
      chain allowing the PEP-dependent phosphorylation of LevR, presumably at His-869.
      This phosphorylation seems to inhibit LevR activity and probably regulates the
      induction of the lev operon. Mutants in which His-869 of LevR has been replaced
      with a non-phosphorylatable alanine residue exhibited constitutive expression
      from the lev promoter, as do levD or levE mutants. In contrast, PEP-dependent
      phosphorylation of LevR in the presence of only the general components of the
      PTS, enzyme I and HPr, regulates LevR activity positively. This phosphorylation
      most probably occurs at His-585. Mutants in which His-585 has been replaced with
      an alanine had lost stimulation of LevR activity and PEP-dependent
      phosphorylation by enzyme I and HPr. This second phosphorylation of LevR at His
      585 is presumed to play a role in carbon catabolite repression.

PMID- 9622355
TI  - Three genes encode distinct AP33 proteins involved in Trichomonas vaginalis
      cytoadherence.
AB  - Adherence to host cells is essential for the initiation and maintenance of
      infection by mucosal pathogens. The protozoan Trichomonas vaginalis colonizes the
      human urogenital tract via four surface proteins (AP65, AP51, AP33 and AP23). To
      characterize AP33 further, six cDNA clones were examined. Restriction mapping
      indicated that the six clones represented three similar genes. Southern analysis
      confirmed the existence of three single-copy AP33 genes and suggested a semi
      conservative genomic arrangement between T. vaginalis isolates. Analysis of full
      length sequences determined that each contained a 930bp open reading frame
      encoding a protein of approximately 33,000 Da. Sequence comparisons revealed a
      high degree of identity at both the DNA and the protein levels. N-terminal
      protein sequencing established the presence of leader peptides. Each of the three
      full-length recombinant proteins had a predicted pI of approximately 10, which
      was verified experimentally for the T. vaginalis AP33 adhesin. A database search
      revealed that AP33 had significant identity to the succinyl-CoA synthetase alpha
      subunit of several different organisms and virtually 100% identity to the
      reported T. vaginalis subunit. Unlike commercially purchased enzyme, the
      recombinant proteins retained adhesive properties equal to the natural T.
      vaginalis AP33. The characteristics of the AP33 protein are similar to those of
      the other adhesins and emphasize a complex host-parasite relationship.

PMID- 9622356
TI  - A novel DNA element that controls bacterial heat shock gene expression.
AB  - The hspArpoH1 and hspBCdegP heat shock operons of Bradyrhizobium japonicum are
      preceded by a novel, conserved DNA element of approximately 100 bp, which is
      responsible for the temperature-regulated transcription of their sigma70-type
      promoters. We designated this motif ROSE for repression of heat shock gene
      expression and found additional ROSE elements upstream of two newly identified
      heat shock operons. A critical core region in the hspA-associated ROSE1 was
      defined by introducing insertions or deletions. While four mutants retained the
      ability to repress transcription of the hspArpoH1 operon, five deletion mutants
      produced elevated hspA mRNA levels under low-temperature growth conditions.
      Derepression was confirmed by increased RpoH1 levels in non-heat-shocked cells
      from one of these mutants and by strains that contained a translational hspA-lacZ
      fusion associated with mutated ROSE1 elements. The hspArpoH1 operon was
      efficiently transcribed in vitro, and a deletion of ROSE1 did not impair this
      activity. Gel retardation experiments demonstrated that a protein in non-heat
      shocked cells specifically binds to the intact ROSE1 element but not to a mutated
      element lacking the core region. Taken together, these results indicate that a
      central region of ROSE serves as a binding site for a repressor protein under
      standard growth conditions in order to prevent the undesired transcription of
      heat shock genes.

PMID- 9622357
TI  - Escherichia coli genes expressed preferentially in an aquatic environment.
AB  - Enteric bacteria are frequently found in aquatic environments, where they may
      pose a risk to human health. Although bacterial survival and persistence in such
      habitats has been studied extensively, there is almost no information about
      bacterial adaptation to these conditions at the level of changes in gene
      expression. As a first exploration of this field, we have carried out a screen
      designed to identify Escherichia coli genes that show increased expression in an
      aquatic environment. The screen was performed by subtractive hybridization on a
      genomic library and led to the identification of several RNA species more
      abundant in cells inoculated in this medium than in stationary-phase cultures
      after growth in rich medium. The genes identified include specific tRNA operons
      and a gene of unknown function, gapC, with similarities to glyceraldehyde-3
      phosphate dehydrogenases. E. coli K-12 strains appear to have accumulated
      mutations in gapC, which may impede its translation, whereas natural isolates
      have an intact gapC gene. Sequence comparison of gapC with related genes suggests
      its acquisition by horizontal gene transfer from gram-positive bacteria.

PMID- 9622358
TI  - Structure of the chromosomal insertion site for pSAM2: functional analysis in
      Escherichia coli.
AB  - The element pSAM2 from Streptomyces ambofaciens integrates into the chromosome
      through site-specific recombination between the element (attP) and the
      chromosomal (attB) sites. These regions share an identity segment of 58bp
      extending from the anti-codon loop through the 3' end of a tRNA(Pro) gene. To
      facilitate the study of the attB site, the int and xis genes, expressed from an
      inducible promoter, and attP from pSAM2 were cloned on plasmids in Escherichia
      coil. Compatible plasmids carrying the different attB regions to be tested were
      introduced in these E. coli strains. Under these conditions, Int alone could
      promote site-specific integration; Int and Xis were both required for site
      specific excision. This experimental system was used to study the sequences
      required in attB for efficient site-specific recombination. A 26 bp sequence,
      centred on the anti-codon loop region and not completely included in the identity
      segment, retained all the functionality of attB; shorter sequences allowed
      integration with lower efficiencies. By comparing the 26-bp-long attB with attP,
      according to the Lambda model, we propose that B and B', C and C' core-type Int
      binding sites consist of 9 bp imperfect inverted repeats separated by a 5 bp
      overlap region.

PMID- 9622359
TI  - Structure of the has operon promoter and regulation of hyaluronic acid capsule
      expression in group A Streptococcus.
AB  - Group A streptococcal strains vary widely in the amount of hyaluronic acid
      capsule they produce, although the has operon, which encodes the enzymes required
      for hyaluronic acid synthesis, is highly conserved. The three genes making up the
      has operon are transcribed from a single promoter located upstream of the first
      gene in the operon, hasA. To investigate transcriptional regulation of capsule
      synthesis, we studied the structure and function of the has operon promoter
      sequences from two strains of group A Streptococcus: a highly encapsulated M-type
      18 strain and a poorly encapsulated M-type 3 strain. Transcriptional fusions of
      the has operon promoter to a promoterless chloramphenicol acetyltransferase gene
      were constructed in a temperature-sensitive shuttle vector. The influence of
      promoter structure on has operon transcription was reflected by chloramphenicol
      acetyl transferase activity in cell lysates of Escherichia coli harbouring the
      recombinant plasmids and in group A Streptococcus after integration of the
      promoter fusions into the streptococcal chromosome. Fusions including as few as
      12 nucleotides upstream from the -35 site of the has promoter exhibited full
      activity, indicating that sequences further upstream do not affect has gene
      transcription. A transcriptional fusion of the has promoter from the highly
      encapsulated M-type 18 strain was threefold more active than a similar construct
      from the poorly encapsulated M-type 3 strain. Analysis of the promoter sequences
      for the two strains revealed differences in three nucleotides in the -35, -10
      spacer region of the promoter and in four nucleotides in the +2 to +8 positions
      relative to the start site of hasA transcription. To determine the relative
      importance of the two groups of nucleotide substitutions, chimeric promoter
      sequences were constructed in which either of the two clusters of variant
      nucleotides from the M18 has promoter was substituted for the corresponding
      positions in the M3 has promoter. Analysis of these chimeric promoter fusions
      showed that sequence changes in both regions influenced promoter strength. These
      results define the limits of cis-acting chromosomal sequences that influence
      transcription of the has operon and indicate that the fine structure of the
      promoter is an important determinant of capsule gene expression in group A
      Streptococcus.

PMID- 9622360
TI  - Sequence, exon-intron organization, transcription and mutational analysis of
      prnA, the gene encoding the transcriptional activator of the prn gene cluster in
      Aspergillus nidulans.
AB  - The prnA gene codes for a transcriptional activator that mediates proline
      induction of four other genes involved in proline utilization as a nitrogen
      and/or carbon source in Aspergillus nidulans. In this paper, we present the
      genomic and cDNA sequence and the transcript map of prnA. The PrnA protein
      belongs to the Zn binuclear cluster family of transcriptional activators. The
      gene shows a striking intron-exon organization, with the putative nuclear
      localization sequence and the Zn cluster domain in discrete exons. Although the
      protein sequence presents some interesting similarities with the isofunctional
      protein of Saccharomyces cerevisiae Put3p, a higher degree of similarity is found
      with a functionally unrelated protein Thi1 of Schizosaccharomyces pombe. A number
      of mutations mapping in the prnA gene were sequenced. This comprises a deletion
      that results in an almost complete loss of the prnA-specific mRNA, a mutation in
      the putative nuclear localization signal, a proline to leucine mutation in the
      second loop of the zinc cluster and a cold-sensitive mutation in the so-called
      'central region'. Other complete or partial loss of function mutations map in
      regions of unknown function. We establish that the transcription of the gene is
      neither self-regulated nor significantly affected by carbon and/or nitrogen
      metabolite repression.

PMID- 9622361
TI  - Regulation of type 1 fimbrial expression in uropathogenic Escherichia coli:
      heterogeneity of expression through sequence changes in the fim switch region.
AB  - Over 80% of uropathogenic Escherichia coli express type 1 fimbriae. Expression is
      phase variable, and regulation of phase switching can differ between isolates.
      Previously, this was explained by differences in the expression of the fim
      recombinases, FimB and FimE. Our study of 50 uropathogenic E. coli isolates
      confirms variation in the regulation of type 1 fimbriae but, in many cases, the
      variation could be accounted for by sequence changes within and adjacent to the
      fim switch, rather than by differences in recombinase expression. This was
      demonstrated by moving the switch from the isolates into an isogenic background
      and comparing the switching behaviour with that of the original isolate. Isolates
      could be arranged into groups based on fim switch regulation and sequence
      similarity. In certain cases, the altered regulation was located to specific
      basepair changes within the fim switch. Sequence changes were found that had a
      marked effect on the activity of either FimB or FimE switching, while others
      affected FimB switching in only one direction. These results emphasize the value
      of using naturally selected sequence variation to further the understanding of
      gene regulation.

PMID- 9622362
TI  - Metronidazole resistance in Helicobacter pylori is due to null mutations in a
      gene (rdxA) that encodes an oxygen-insensitive NADPH nitroreductase.
AB  - Metronidazole (Mtz) is a critical component of combination therapies that are
      used against Helicobacter pylori, the major cause of peptic ulcer disease. Many
      H. pylori strains are Mtz resistant (MtzR), however, and here we show that MtzR
      results from loss of oxygen-insensitive NADPH nitroreductase activity. The
      underlying gene (called 'rdxA') was identified in several steps: transformation
      of Mtz-susceptible (MtzS) H. pylori with cosmids from a MtzR strain, subcloning,
      polymerase chain reaction (PCR) and DNA sequencing. We also found that (i) E.
      coli (normally MtzR) was rendered MtzS by a functional H. pylori rdxA gene; (ii)
      introduction of rdxA on a shuttle vector plasmid into formerly MtzR H. pylori
      rendered it MtzS; and (iii) replacement of rdxA in MtzS H. pylori with an
      rdxA::camR null insertion allele resulted in a MtzR phenotype. The 630 bp rdxA
      genes of five pairs of H. pylori isolates from infections that were mixed
      (MtzR/MtzS), but uniform in overall genotype, were sequenced. In each case, the
      paired rdxA genes differed from one another by one to three base substitutions.
      Typical rdxA genes from unrelated isolates differ by 5% in DNA sequence.
      Therefore, the near identity of rdxA genes from paired MtzR and MtzS isolates
      implicates de novo mutation, rather than horizontal gene transfer in the
      development of MtzR. Horizontal gene transfer could readily be demonstrated under
      laboratory conditions with mutant rdxA alleles. RdxA is a homologue of the
      classical nitroreductases (CNRs) of the enteric bacteria, but differs in cysteine
      content (6 vs. 1 or 2 in CNRs) and isoelectric point (pI=7.99 vs. 5.4-5.6), which
      might account for its reduction of low redox drugs such as Mtz. We suggest that
      many rdxA (MtzR) mutations may have been selected by prior use of Mtz against
      other infections. H. pylori itself is an early risk factor for gastric cancer;
      the possibility that its carcinogenic effects are exacerbated by Mtz use, which
      is frequent in many societies, or the reduction of nitroaromatic compounds to
      toxic, mutagenic and carcinogenic products, may be of significant concern in
      public health.

PMID- 9622363
TI  - High-affinity binding sites for the initiator protein DnaA on the chromosome of
      Escherichia coli.
AB  - The initiator protein DnaA of Escherichia coli binds with unusually high affinity
      to five regions on the chromosome, in addition to the replication origin, oriC.
      Using a solid-phase DNA binding assay, in which the DNA binding C-terminal domain
      of DnaA is bound via a biotin tag to magnetic beads, we could fish only fragments
      with these six regions from different chromosomal digests. Except for oriC, these
      fragments contain only one or two consensus DnaA binding sites, DnaA boxes. The
      distribution of these high-affinity DnaA boxes on the chromosome is random.

PMID- 9622364
TI  - Abundance of Lutzomyia ovallesi but not Lu. gomezi (Diptera: Psychodidae)
      correlated with cutaneous leishmaniasis incidence in north-central Venezuela.
AB  - In north-central Venezuela Lutzomyia gomezi and Lu. ovallesi are the main
      endophilic/anthropophilic species of phlebotomine sandflies implicated as vectors
      of cutaneous leishmaniasis (CL). Lutzomyia ovallesi has been found infected with
      Leishmania braziliensis (1.2%) and less often with Le. mexicana (0.07%), while
      Le. braziliensis infections have also been found in Lu. gomezi (0.47%). We
      investigated population densities of these sandflies using two sampling methods
      with four series of collections between January 1991 and March 1995 at El
      Ingenio, Miranda State. All-night outdoor collections from a Shannon trap were
      correlated with indoor collections from CDC light-traps by linear regression,
      which proved to be statistically significant for both species. Estimated numbers
      of female sandflies per house per night were found to be proportional to monthly
      precipitation (i.e. rainfall), with a lag time of seven months for Lu. ovallesi
      and of six months for Lu. gomezi. Predominance of Lu. ovallesi over Lu. gomezi
      (c. 10:1) was observed throughout the year, with the number of infected females
      estimated as 0.043+/-0.047 Lu. ovallesi and 0.0085+/-0.0124 Lu. gomezi per CDC
      trap per house per night (ratio approximately 5:1). The mean rate of new CL cases
      per house per year and sandfly abundance were correlated by linear regression,
      showing a statistically significant relationship for Lu. ovallesi but not for Lu.
      gomezi. The negative intercept indicated that, on average, the CDC trap density
      exceeds 800 Lu. ovallesi females/house/year before new CL cases occur at El
      Ingenio.

PMID- 9622365
TI  - Stomodaeal valve ultrastructure in the sandfly Lutzomyia longipalpis (Diptera:
      Psychodidae).
AB  - The stomodaeal valve and adjacent cardia region of the alimentary canal of the
      phlebotomine sandfly Lutzomyia longipalpis have been studied using electron
      microscopy. With the scanning electron microscope (SEM), numerous pit-like
      structures of different sizes were found in the surface of the valve of male and
      female flies. Under the transmission electron microscope (TEM), the cells
      adjacent to the pores were shown to have numerous mitochondria and to lack neural
      innervation. It is suggested that the pit-like structures are probably secretory.
      A typical basiconic sensilla was found on the inner side of the oesophagus at the
      junction with the stomodaeal valve, with at least one dendrite which extended to
      the tip, indicating a chemosensory role. It is likely that this type of sensilla
      may control the movement of the stomodaeal valve after contact with fluids
      entering the mid-gut and may be responsible for diverting the sugar meal to the
      crop by closure of the valve.

PMID- 9622366
TI  - Differential responses of mosquito sibling species Anopheles arabiensis and An.
      quadriannulatus to carbon dioxide, a man or a calf.
AB  - Field studies on responses of two mosquito sibling species, Anopheles arabiensis
      Patton and An. quadriannulatus Theobald, to a man, a calf and different release
      rates of carbon dioxide (man, calf and cow equivalents) were conducted in north
      eastern South Africa. Various combinations of baits were compared in two-choice
      tests, using two mosquito nets, placed 2.5 m apart and 10 cm off the ground.
      Mosquitoes attracted to the baits were able to enter the nets from below and were
      collected by means of a suction tube. In a two-choice test between a man and CO2
      (human equivalent, 250 ml/min), 81% of the An. quadriannulatus were caught with
      CO2. The reverse was seen for An. arabiensis, where only 20% of the total catch
      was caught with CO2 compared to man. High release rates of CO2 (cow equivalent,
      800 ml/min) attracted significantly more An. quadriannulatus than the low release
      rate (250 ml/min), whereas no significant effect of the release rate of CO2 on
      the total catch of An. arabiensis was seen. In the latter species, up to 33% of
      the attraction of human emanation is attributable to carbon dioxide. Anopheles
      quadriannulatus was equally attracted to a calf and CO2 (calf equivalent, 180
      ml/min). Catches of other mosquito species showed consistent differences between
      all treatments which appear to be associated with differences in host-preference,
      suggesting that the importance of CO2 in host-seeking behaviour of mosquitoes
      increases with the degree of zoophily.

PMID- 9622367
TI  - Efficacy of tags impregnated with pheromone and acaricide for control of
      Amblyomma variegatum.
AB  - The efficacy of tags impregnated with pheromone and acaricide for control of
      Amblyomma variegatum on cattle in Guadeloupe was determined for a 13-week trial.
      Comparisons were made between untreated cattle and cattle with tags containing
      either pheromones alone (o-nitrophenol, methyl salicylate, 2,6-dichlorophenol and
      phenylacetaldehyde), pheromones plus acaricide (cyfluthrin or deltamethrin), or
      acaricide alone. Tags were fastened to cattle both on collars on the neck and
      with adhesive to tail hairs, with over 98 and 90% of tags retained, respectively,
      during the trial. By the end of the trial, tick infestations increased on
      untreated cattle (311.7%) and cattle with pheromone tags (154.8%) but decreased
      on cattle with pheromone/ cyfluthrin (-45.0%), cyfluthrin (-42.8%),
      pheromone/deltamethrin (-68.7%) and deltamethrin tags (-87.6%). Cattle with
      pheromone tags had greater proportions of ticks on the hind regions (81%)
      compared to untreated cattle (62.5%) and on the front regions (18.2%) compared to
      untreated cattle (8.2%) indicating that ticks aggregated in response to
      pheromones. Analysis of hair samples by gas chromatography indicated that, within
      2 days of placement, cyfluthrin spread rapidly over the body from the tags. Both
      cyfluthrin and deltamethrin were present in detectable levels on all eight body
      regions examined throughout the trial. Analysis of the tags indicated that they
      all still contained pheromone components after 13 weeks under field conditions.

PMID- 9622368
TI  - Sandfly midgut lectin: effect of galactosamine on Leishmania major infections.
AB  - Galactosamine, which has been shown in vitro to specifically inhibit sandfly
      midgut lectin activity, was fed to Phlebotomus duboscqi females with blood
      containing promastigotes of Leishmania major. Non-inhibitory sugar, galactose,
      was added in controls. For two strains of L. major (LV 561 and Neal-P),
      galactosamine substantially enhanced the establishment of infection in the
      sandfly posterior midgut and significantly increased parasite loads after
      defaecation, but did not affect anterior migration of Leishmania. On day 3 post
      infection, most infections in galactosamine-fed sandfly groups (92% of LV 561 and
      100% of Neal-P) were found in the ectoperitrophic space of the posterior midgut,
      whereas most infections in the galactose-fed groups of sandflies (85% in LV 561
      and 96% in Neal-P) were restricted to the peritrophic sac. On day 9, however, the
      proportion of infections colonizing the stomodeal valve was similar in both
      dietary groups of sandflies for both strains of L. major. The addition of
      galactosamine prevented the decrease of parasite loads which occurred in controls
      between days 3 and 6 post-infection. On days 6 and 9, heavy infections were
      observed almost exclusively in galactosamine-fed females. Differences between
      groups were more pronounced for the Neal-P strain, which normally developed
      poorly in sandflies. Morphology of L. major LV 561 was not affected by
      galactosamine supplement: the lengths of parasite body and flagellum were similar
      in both sandfly groups. Two hypotheses are considered for the role of sandfly
      midgut lectin in Leishmania development in the vector midgut. One proposes that
      sandfly lectin kills Leishmania promastigotes, the other assumes that lectin
      blocks LPG-mediated binding of promastigotes to sandfly midgut microvilli.

PMID- 9622369
TI  - Culicoides in relation to transmission of African horse sickness virus in The
      Gambia.
AB  - Twelve light trap collections made near overnight shelters of horses and donkeys
      in four villages in the Central River Division of The Gambia captured fourteen
      species of biting midge of the genus Culicoides. Five species new to The Gambia
      were identified. This brought the number of recognized species of Culicoides
      (after a revision of C. schultzei) to twenty-nine in The Gambia. Species known or
      suspected as vectors of African horse sickness virus (AHSV) and bluetongue virus
      (BTV) comprised 83% of female captures, 65% of captures being C. imicola or its
      sibling species, C. miombo. Captures of female Culicoides in the late dry season
      were almost as large as in the early dry season, despite the extreme heat and
      dryness at this time of the year. Tests on batches of formalin-preserved female
      midges, using AHSV or BTV antigen capture ELISAs, did not show the presence of
      any virus amongst 2286 females in 240 aliquots. Nearly all Gambian equines are
      reportedly seropositive to AHSV and these results suggest that virus challenge
      from Culicoides vectors may be a factor in the health of Gambian horses and
      donkeys.

PMID- 9622370
TI  - Morphology of the second- and third-instar larvae of Dermatobia hominis by
      scanning electron microscopy.
AB  - Larvae of Dermatobia hominis 10-27 days old were collected from experimentally
      infected rats and their morphology was studied by scanning electron microscopy.
      The moult from the second to third instar occurs at 18 days, with emergence from
      the host at 30 days post-infection. The second-instar larvae bear on the
      pseudocephalon, antennae (coeloconic sensilla), and coeloconic and basicoconic
      sensilla on the maxillary sensory complex. The thoracic segments bear small
      backwardly-directed spines anteriorly and ventral trichoid and campaniform
      sensilla. The first four abdominal segments have small and large backwardly
      directed spines that are absent on segments five and six. The seventh and eighth
      abdominal segments have medium-sized forwardly-directed spines. Abdominal
      segments are encircled by campaniform sensilla. The terminal end of the eighth
      abdominal segment bears the anus, prominent anal lobes and two spiracular
      openings on each spiracular plate. Spiracular plates show a radial sun ray
      pattern. The rear abdomen also bears an ecdysal aperture, several pores and eight
      coeloconic sensilla. Although there are slight morphological differences, the
      spines (predominantly flat and thorn-like) and sensilla (campaniform and
      coeloconic) of the third-instar larvae show a similar arrangement to that of
      second-instar larvae. Thoracic trichoid sensilla are not seen in third-instar
      larvae. A perispiracular gland aperture is situated above each posterior
      spiracular opening. These morphological features are compared with those of other
      cuterebrid larvae.

PMID- 9622371
TI  - Host preferences of tsetse (Diptera: Glossinidae) based on bloodmeal
      identifications.
AB  - An enzyme-linked immunosorbent assay (ELISA) was developed to identify the origin
      of vertebrate blood in the guts of 29 245 wild-caught flies of eleven Glossina
      species from various ecological zones of Africa. Depending on the quality of the
      bloodmeal samples, 62.8% of the samples were identified and could be assigned to
      a host-group (e.g. ruminant), family (e.g. Bovidae) or species (e.g. Bos spp.). A
      total of 13 145 samples (44.9%) was identifiable up to the species level. With a
      few exceptions, the present results are in agreement with earlier published
      reports. Glossina austeni and G. fuscipleuris seemed to have a distinct feeding
      preference for Suidae (mainly bushpig). Glossina morsitans ssp. fed mainly on
      Suidae (mainly warthog), although local variations were observed and in some
      areas hippopotamus or ruminants replaced the warthog as the main host. Bushbuck
      seemed to be the principal food source for G. longipalpis and G. fusca. Glossina
      pallidipes fed mainly on ruminants (buffalo, bushbuck and cattle) but, depending
      on host availability and location, Suidae were also important hosts. Hippopotamus
      was identified as the main source of bloodmeals for G. brevipalpis. The main
      hosts for G. longipennis were Suidae (mainly bushpig) and not rhinoceros as had
      been reported 40 years earlier. The opportunistic feeding behaviour of the
      palpalis tsetse group was confirmed. The results showed that changes in
      environment, fauna and host availability may result in modification of tsetse
      feeding patterns.

PMID- 9622372
TI  - Comparative scanning electron microscopy of third-instar Hypoderma spp. (Diptera:
      Oestridae).
AB  - Scanning electron microscope study of third-instar larvae of four species of
      Hypoderma revealed differences among species in the pattern of spination, spine
      morphology and morphology of the spiracular plates. These observations identify
      characters that enable the differentiation of Hypoderma actaeon and H. diana,
      parasitizing red deer (Cervus elaphus) in Europe, and provide additional
      characters for differentiating H. bovis and H. lineatum parasitizing cattle.

PMID- 9622373
TI  - Characterization of amplified esterase Estbeta1(2) associated with
      organophosphate resistance in a multi-resistant population of the mosquito Culex
      quinquefasciatus from Cuba.
AB  - Esterase amplification is the major organophosphorus (OP) insecticide resistance
      mechanism in Culex mosquitoes. The amplified Estalpha2(1)?Estbeta2(1) esterases
      are found in > 90% of resistant populations worldwide, whereas amplified DNAs
      (amplicons) containing Estbeta1s are much rarer. Individuals with the Estbeta1
      amplicons appear to be at a selective disadvantage in competition with those
      carrying the Estalpha2(1)?Estbeta2(1) amplicons. To test the hypothesis that this
      is because Estbeta1 is less able to bind insecticide than the common amplified
      esterases, Estbeta1(2) was purified from the multi-resistant Habana strain of
      Culex quinquefasciatus, from Cuba. In its native form Estbeta1 is a monomeric
      enzyme of 66 kDa, with a pI of 4.8. The bimolecular rate constants for
      interaction of Estbeta1(2) with several OP insecticides were similar to those for
      the commonly elevated esterases Estalpha2(1) and Estbeta2(1), and much higher
      than for the electrophoretically identical non-elevated Estbeta1(3) and
      Estalpha3. Hence the apparent selective advantage of the Estalpha2(1)?Estbeta2(1)
      amplicon is not due to its greater efficiency of insecticide binding, as OP
      insecticides are significantly better inhibitors of all the amplified esterases
      than of their non-amplified counterparts and therefore should be equally
      effective at conferring resistance.

PMID- 9622374
TI  - Increasing parasitism by the German yellow jacket wasp, Paravespula germanica, on
      dairy cattle in Israel.
AB  - During the past two decades, parasitism by the German yellow jacket wasp,
      Paravespula germanica, on lactating dairy cattle has occurred in Israel during
      August to October annually, affecting up to 65% of cows in certain herds. The
      nibbled and exposed tissues of teats and sometimes udders become infested by
      bacteria, especially Streptococcus dysgalactiae and Actinomyces pyogenes, causing
      clinical and subclinical mastitis. Normally, German wasps are primarily insect
      predators, but the urbanization around many dairy farms has reduced open space
      and associated standard food sources, i.e. insects, plants and carcasses. This
      has resulted in P. germanica nesting more often on dairy farms. In some
      instances, when high densities of P. germanica correspond with scarcity of prey,
      a segment of the wasp population preys primarily on the older and heavier cows
      with weak defensive behaviour. The teat feeding colonies of P. germanica may have
      an advantage, in that they are less dependent on fluctuations in the number of
      prey insects.

PMID- 9622375
TI  - Factors affecting the landing and feeding responses of the tsetse fly Glossina
      pallidipes to a stationary ox.
AB  - In Zimbabwe, studies were made of the landing and feeding responses of Glossina
      pallidipes on an ox. Of the tsetse approaching an ox, approximately 70% fed.
      Increasing densities of tsetse increased the grooming responses of the ox but had
      no significant effect on the percentage of tsetse that engorged. The landing site
      of tsetse on the ox varied with density, with approximately 50% landing on the
      legs at low densities (< 20 flies per ox), compared to approximately 80% at
      densities > 40 flies per ox. For male G. pallidipes, the mean bloodmeal size was
      37 mg. The probability of feeding was negatively correlated with fat content,
      declining from 91% for flies with < 1 mg fat to < 50% for flies with > 4 mg fat.
      Bloodmeal size was also negatively correlated with fat content; the regression
      equation relating bloodmeal size and fat content indicated that the mean wet
      weight declined from 42 mg for flies with 1 mg of fat to 31 mg for flies with 5
      mg of fat. For females, the probability of feeding was not significantly affected
      by age as determined by ovarian category but there was a paucity of young
      (ovarian category 0) flies attracted to the ox. Pregnancy status had no
      significant effect on the probability of feeding, but samples of flies attracted
      to the ox showed a relative dearth of females approaching larviposition and a
      preponderance just after.

PMID- 9622376
TI  - Preliminary investigations of plasma ammonia levels in sheep infested with
      Lucilia sericata and their potential in the ageing of blowfly lesions in cases of
      neglect.

PMID- 9622377
TI  - Comparative susceptibility of Glossina longipennis and G. brevipalpis to
      pathogenic species of Trypanosoma.

PMID- 9622378
TI  - Ixodes frontalis on the Baltic island of Gotland, Sweden.

PMID- 9622379
TI  - Differential alteration of adenylyl cyclase subtypes I, II, and V/VI in
      postmortem human brains of heroin addicts.
AB  - In animal and culture cell experiments, the upregulation of cAMP-related signal
      transduction after chronic opioid administration has been hypothesized to be an
      adaptive change of the molecular mechanism to maintain homeostasis in
      intracellular signals downstream from opioid receptors. Herein, we have examined
      the quantitative changes of three adenylyl cyclase (AC) subtypes (I, II, and
      V/VI) in temporal cortex membranes from brains of heroin addicts and age-matched
      controls by immunoblotting. The immunoreactivity of AC-I decreased significantly
      (p < 0.05) in heroin addicts, compared with controls; whereas those of AC-II and
      AC-V/VI were not changed. The present findings indicate that differential
      regulation of AC subtypes occurs and that AC-I may play an important role in the
      signal transduction for opiate-induced tolerance and dependence mechanisms in
      human brain cortex.

PMID- 9622380
TI  - Reduced immunoreactivity of type I adenylyl cyclase in the postmortem brains of
      alcoholics.
AB  - Reduced adenylyl cyclase activity after chronic ethanol exposure has been
      reported. In this study, we investigated by immunoblotting whether quantitative
      changes of adenylyl cyclase isoforms (type I, type II, and type V/VI adenylyl
      cyclases) exist in membrane preparations of the temporal cortex obtained from six
      alcoholics and six age-matched controls. The immunoreactivity of type I adenylyl
      cyclase decreased significantly in the temporal cortex of alcoholics when
      compared with controls (p < 0.05), whereas those of type II and type V/VI
      adenylyl cyclases showed no changes between the groups. These findings suggest
      that these isoform-specific afterations in the adenylyl cyclase system may be
      involved in the pathophysiology of alcoholism.

PMID- 9622381
TI  - A new genetic variant in the Sp1 binding cis-element of cholecystokinin gene
      promoter region and relationship to alcoholism.
AB  - Neuropeptide cholecystokinin (CCK) and the CCK receptors in the central nervous
      system mediate actions on increasing firings, anxiety, and nociceptions.
      Furthermore, CCK modulates the release of dopamine and dopamine-related behaviors
      in the mesolimbic pathway. In our study, genetic variation in the promoter and
      coding regions of the prepro-CCK gene were analyzed among 66 Japanese, 66
      American Whites, 54 Chinese, and 41 Colombian natives. Two nucleotide sequence
      variants were found: a frequent mutation at nucleotide position -45 C to T
      involved in core sequence of Sp1 binding cis-element of the promoter region, and
      a C to T substitution at the 1662 position in intron 2. Analysis for the
      segregation study in 10 families of twins confirmed codominant heredity of two
      alleles. Distribution of genotypes and gene frequencies of 66 controls and 108
      alcoholics in Japan presented that allelic variant T type in alcoholics was found
      in higher frequencies than that of controls, and distribution of these genotypes
      was significantly different between the both groups.

PMID- 9622382
TI  - Relationship between platelet membrane lipid compositions and platelet
      aggregability in alcoholic liver disease.
AB  - We studied the relationship between changes in platelet aggregability and
      platelet membrane lipid in alcoholic liver disease. The maximal rate of ADP
      induced platelet aggregation was significantly increased in the alcoholic liver
      disease group than in the control group. No significant difference was observed
      in the maximal rate of collagen-induced platelet aggregation. However, a lag time
      required for the start of platelet aggregation was significantly shortened in the
      alcoholic liver disease group, indicating increased platelet aggregability.
      Results of the platelet aggregation test suggested that alcoholic liver disease
      patients have their platelet aggregation affected by the abnormality of
      prostaglandin metabolism. The alcoholic liver disease group was further divided
      into two subgroups: the hyperaggregation group and the unchanged aggregation
      group. Both free cholesterol and phospholipid in the platelet membrane were
      significantly increased in the alcoholic liver disease group. In phospholipid
      compositions, phosphatidylserine plus phosphatidylinositol were significantly
      decreased in the alcoholic liver disease group, whereas a significant decrease in
      phosphatidylserine plus phosphatidylinositol was observed in the hyperaggregation
      group of alcoholic liver disease. Analysis of fatty acid compositions of platelet
      membrane showed significantly decreased palmitic acid in the alcoholic group.
      There was no significant change of arachidonic acid, which directly affects
      platelet aggregation. Eicosapentaenoic acid significantly decreased in the
      alcoholic liver disease group, but there was no difference in docosahexaenoic
      acid. Meanwhile, the thrombogenic index, calculated from the fatty acids of
      platelet membrane, showed no difference between the alcoholic liver disease group
      and the control group. However, the thrombogenic index was significantly
      increased in the hyperaggregation group than in the unchanged aggregation group.
      These data suggested that platelet aggregation is affected by not only a change
      in arachidonic acid, but also changes in fatty acid compositions of the platelet
      membrane.

PMID- 9622383
TI  - Abnormality of very long-chain fatty acids of erythrocyte membrane in alcoholic
      patients.
AB  - Profiles of very long-chain fatty acids were studied in the erythrocyte membrane
      of five alcoholic patients. We identified three fatty acids as cis-16
      pentacosenoic acid (C25:1), cis-17-hexacosenoic acid (C26:1), and hexacosenoic
      acid (C26:1), and hexacosanoic acid (C26:0) by gas chromatography-mass
      spectrometry. The ratios of C26:1/C22:0, C26:0/C22:0, C24:1/C22:0, and
      C24:0/C22:0 were increased. These findings suggest that active oxygen species or
      free radicals generated by chronic alcohol consumption in alcohol patients
      interrupt the peroxisomal beta-oxidation of fatty acids, because very long-chain
      fatty acids are mainly metabolized by the peroxisomal beta-oxidation system. This
      is the first study showing accumulation of very long-chain fatty acids in the
      erythrocyte membrane of alcoholic patients.

PMID- 9622384
TI  - Mitochondrial dysfunction of human muscle in chronic alcoholism detected by using
      31P-magnetic resonance spectroscopy and near-infrared light absorption.
AB  - We previously examined the effect of alcohol on muscle energy metabolism in
      chronic alcoholics by using 31P-magnetic resonance spectroscopy. Measurements of
      intracellular pH and PCr index [PCr/(PCr + Pi)] during resting, hand grasping,
      and recovery in the left flexor digitorum superficialis muscle of alcoholics with
      neurological signs showed a marked decrease and delayed recovery of pH, but rapid
      recovery of PCr index indicating that the muscle produces lactate during and
      after exercise to maintain the ATP level. To clarify the reason for this
      preference for anaerobic metabolism, we conducted simultaneous measurements of
      the muscle blood supply during and after exercise by using the near-infrared
      light method and energy metabolism by using 31P-magnetic resonance spectroscopy.
      In alcoholics with neurological signs, we observed a significant increase of
      oxyhemoglobin after exercise with a slight increase of total hemoglobin. In
      healthy volunteers and chronic alcoholics without neurological signs, such an
      overshoot of oxyhemoglobin was not observed. We conclude that chronic alcoholics
      with neurological signs have an abnormality of aerobic metabolism owing to muscle
      mitochondrial dysfunction.

PMID- 9622385
TI  - Oxidative stress and mitochondrial damage precedes gastric mucosal cell death
      induced by ethanol administration.
AB  - Although it has been speculated that active oxidants and mitochondrial membrane
      damages play roles in ethanol-induced gastric mucosal damages, its detail remains
      unknown. The present study was designed to investigate whether ethanol induces
      oxidative stress and mitochondrial permeability transition (MPT) before cell
      death of gastric mucosal cells. Rat gastric mucosal cells (RGM-1) were kept in
      serum-free Dulbecco's modified Eagle's medium before addition of various
      concentrations of ethanol. Nuclear morphological aftemations and membrane barrier
      dysfunction of RGM-1 cells were assessed by staining with Hoechst 33342 and
      propidium iodide, respectively. To assess the contribution of oxygen-derived free
      radicals and intracellular glutathione, scavenger of hydrogen peroxide and the
      hydroxyl radical, N,N-dimethylthiourea, glutathione precursor, N-acetyl-L
      cysteine, and an inhibitor of alcohol dehydrogenase, 4-methylpyrazole were added
      before treatment with ethanol. To investigate MPT, calcein and
      tetramethylrhodamine methyl ester were loaded before addition of ethanol, and the
      changes of fluorescence intensity were monitored using a laser scanning confocal
      microscope. Ethanol (>5% v/v) dose-dependently increased the number of propidium
      iodide-positive cells, suggesting a diminished barrier function of cell membrane.
      After addition of ethanol, mitochondria were filled quickly with calcein
      indicating MPT, which was accompanied by mitochondrial depolarization, as shown
      by loss of tetramethylrodamine methyl ester before cell death. Ethanol-induced
      cell death was significantly attenuated by simultaneous incubation with either
      N,N-dimethylthiourea or N-acetyl-L-cysteine, suggesting the importance of
      intracellular redox states in inducing cellular damage, whereas such change was
      not attenuated by 4-methylpyrazole. Present results suggest that ethanol
      treatment induces intracellular oxidative stress and produces MPT and
      mitochondrial depolarization, which are preceding cell death in gastric mucosal
      cells. Intracellular antioxidants, such as glutathione, may have a significant
      protective action against ethanol in gastric mucosal cells.

PMID- 9622386
TI  - Appearance of myofibroblasts in the gastric mucosa after ingestion of ethanol and
      lansoprazole with reevaluation of the mucoid cap.
AB  - The mucoid cap is important in the restitution of surface epithelial cells of the
      gastric mucosa. We conducted the present study to clarify the relationship of the
      mucoid cap and the myofibroblasts in the course of healing of the gastric mucosa
      with ethanol-induced damage. The effect of lansoprazole on ulcer healing was also
      evaluated. Wistar strain male rats were administered ethanol (50%) by gastric
      intubation. Thirty minutes later, either an aqueous solution of lansoprazole
      (LPZ; 10 mg/100 g of body weight), or the same amount of physiological saline was
      administered by gastric intubation. Localization of the myofibroblasts was
      evaluated at 1, 3, and 12 hr after LPZ treatment, and compared with the number
      and localization of cells positive for rhodamine-phalloidin. The concentration of
      basic fibroblast growth factor (FGF) was determined by EUSA. We observed PR 2D3
      immunoreactive cells in the lamina propria mucosae of the control fundus that
      were weakly positive or negative for rhodamine-phalloidin. Erosive lesions
      reaching more than half of the whole gastric mucosal layer were induced 1 hr
      after ethanol ingestion. An abundance of PR 2D3 and rhodamine-phalloidin double
      positive cells was present in the lamina propria mucosae just below the erosive
      lesion. The administration of LPZ brought about an increase in bFGF
      concentration, an acceleration of ulcer healing, and an increase in
      immunoreactivity to PR 2D3. In conclusion, LPZ strongly influenced the healing of
      gastric mucosal damage related to ethanol administration, possibly through an
      increase in the concentration of bFGF. The immunophenotype of the myofibroblasts
      changed to the muscle type during healing, suggesting an involvement of these
      cells in ulcer healing.

PMID- 9622387
TI  - Long-term alcohol effects on hepatic phosphoglucomutase activities in relation to
      posttranslational modification of the protein.
AB  - ADP-ribosylation is a posttranslational protein modification catalyzed by two
      classes of enzymes: mono-ADP-ribosyltransferase and poly-ADP-ribose polymerases.
      We previously demonstrated that long-term alcohol intake remarkably enhanced an
      endogenous ADP-ribosylation of a 58 kDa protein in rat liver and also identified
      the 58 kDa protein as phosphoglucomutase (PGM). To assess biological significance
      of this phenomenon, we tested the effects of long-term alcohol intake on PGM
      activities in connection with posttranslational modification of the protein. ADP
      ribosylation of PGM was mono- rather than poly-ADP-ribosylation. Also,
      nonenzymatic binding of ADP-ribose was excluded. It was of note that ADP
      ribosylation of exogenous PGM was remarkably increased by adding rat liver plasma
      membranes, and that the extent of the increase was greater in alcohol-fed rats
      than in pair-fed controls. Furthermore, PGM activities were significantly
      increased after long-term alcohol intake concomitant with increased ADP
      ribosyltransferase activities toward PGM. In view of the variety of roles of PGM
      in the liver, such as carbohydrate metabolism and Ca2+ homeostasis, it is
      tempting to speculate that increased ADP-ribosylation of PGM may play a role in
      long-term alcohol effects on hepatocytes.

PMID- 9622388
TI  - Relationship between glutathione and polyamine metabolism after partial
      hepatectomy in alcohol-treated rats.
AB  - In a liver regeneration inhibiting model after partial hepatectomy in rats, we
      determined hepatic glutathione concentration and studied its relation with
      polyamine, an indicator of liver regeneration. Experiment 1: Male ODS rats and
      Wistar rats as control were maintained with vitamin C-deficient diets for 2
      weeks. In the alcohol group, 3 g/kg of ethanol was administered orally 1 hr
      before partial hepatectomy. Experiment 2: Wistar rats were divided into four
      groups, according to the presence or absence of alcohol and vitamin E (VE), and a
      6-week pair-feeding was done. As for partial hepatectomy, about 70% of the total
      liver was excised. As a result, in experiment 1, hepatic glutathione levels were
      significantly decreased by acute alcohol administration in both ODS and Wistar
      rats, and its level of alcohol administration group of ODS rats was the lowest.
      Hepatic ornithine decarboxylase activity and putrescine level 4 hr after partial
      hepatectomy showed almost a similar behavior, being the lowest in the alcohol
      administration group of ODS rats. In experiment 2, hepatic glutathione level
      showed no influence by chronic alcohol administration, but was the lowest in the
      VE-deficient alcohol administration group. Hepatic ODC activity and putrescine
      level 4 hr after partial hepatectomy showed no influence by chronic alcohol
      administration, but was the lowest in the VE-deficient alcohol administration
      group. These results clarified that intrahepatic glutathione levels before
      partial hepatectomy were decreased in the models in which hepatic ODC activities
      after surgery were suppressed.

PMID- 9622389
TI  - Effect of chronic ethanol feeding on endotoxin-induced hepatic injury: role of
      adhesion molecules on leukocytes and hepatic sinusoid.
AB  - Endotoxin is postulated to be an important aggravating factor for alcoholic liver
      disease. We have previously reported that rats fed ethanol are more vulnerable to
      endotoxin-induced liver damage, and hepatic microcirculatory disturbance plays an
      important role for this liver damage by observation with an intravital
      microscopy. In this study, we have investigated the role of adhesion molecules in
      endotoxin-induced microcirculatory disturbance in chronic ethanol-fed rats. Male
      Wistar rats were pair-fed with ethanol liquid diet (ethanol group) or an
      isocaloric control diet (control group) for 6 weeks. Leukocyte adherence to the
      hepatic sinusoid by stimulation with lipopolysaccharides (1 mg/kg of body weight)
      was observed by an inverted fluorescence microscopy equipped with a silicon
      intensified target camera and was found to be enhanced in ethanol-fed rats. Tumor
      necrosis factor-alpha and GRO/CINC-1 (rat counterpart of interleukin-8) was
      increased in the blood in these animals. Subsequent expression of adhesion
      molecules, LFA-1 beta-chain on leukocytes were demonstrated by flow cytometry,
      which suggests a possible involvement of leukocyte adherence to the hepatic
      damage in ethanol-fed animals. Preadministration of anti-rat LFA-1 beta-chain
      monoclonal antibody effectively suppressed leukocyte adherence to the hepatic
      sinusoid. These results suggest that the enhanced sequestration of neutrophils to
      the liver with these adhesion molecules may play a significant role in the
      pathogenesis of alcoholic liver disease.

PMID- 9622390
TI  - Formation of superoxide anion in the hepatic sinusoid after lipopolysaccharide
      challenge.
AB  - Using the cytochrome c method, superoxide anion that is released into the hepatic
      sinusoid was measured after a lipopolysaccharide challenge in a liver perfusion
      system. Moreover, damages of epithelial cells of the hepatic sinusoid were
      estimated with scanning electron microscopic analysis and levels of purine
      nucleoside phosphorylase/GPT ratio. Lipopolysaccharide administration increased
      the conversion of oxidized cytochrome c into reduced cytochrome c in the
      perfusate, indicating that superoxide anion was formed in the hepatic sinusoid.
      This change was associated with increase in levels of portal tumor necrosis
      factor-alpha and attenuated by the simultaneous administration of superoxide
      dismutase. Scanning electron microscope analysis revealed that diameters of
      sinusoidal fenestrae increased in rats treated with lipopolysaccharide, compared
      with controls. Moreover, levels of purine nucleoside phosphorylase/GPT ratio was
      significantly increased in the liver perfusate in lipopolysaccharide-treated
      rats, compared with controls. Superoxide anion in hepatic sinusoid may be one of
      the pathogenic factors behind damages of epithelial cells of the hepatic sinusoid
      caused by lipopolysaccharide.

PMID- 9622391
TI  - Influence of alcohol on branched-chain amino acid/tyrosine molar ratio in
      patients with cirrhosis.
AB  - We investigated whether the reduction of plasma tyrosine in alcoholic liver
      disease would affect the branched-chain amino acid/tyrosine molar ratio (BTR)
      measured using an enzymatic assay method in alcoholic cirrhosis. BTR values were
      higher in patients with compensated and decompensated alcoholic cirrhosis (5.68
      +/- 2.29 and 3.28 +/- 0.75) due to reduction of the tyrosine level relative to
      those in patients with nonalcoholic cirrhosis (3.64 +/- 1.22 and 2.53 +/- 0.99).
      A decrease in tyrosine level and an increase in BTR value were observed after
      single ethanol administration to healthy subjects. As significant elevation of
      serum immunoreactive insulin levels followed elevation of serum glucose levels
      after alcohol loading, it was thought that insulin accelerated intrahepatic
      metabolism of aromatic amino acids, resulting in reduction of the tyrosine level.
      The same mechanism may be applied to tyrosine reduction in patients with
      alcoholic cirrhosis during heavy drinking.

PMID- 9622392
TI  - Correlation of a polymorphism in the interleukin-1 receptor antagonist gene with
      hepatic fibrosis in Japanese alcoholics.
AB  - The aim of this study was to determine whether there is any association between
      interleukin-1 receptor antagonist (IL1-Ra) genotype and alcoholic liver disease.
      The IL1-Ra genotype was assessed in 102 Japanese male alcoholic liver disease
      patients and 46 healthy subjects by polymerase chain reaction with leukocyte DNA.
      The distribution of IL1-Ra genotype and the allelic frequencies in Japanese
      healthy subjects are both significantly different from that previously reported
      in Caucasians (A1/A1 genotype: 95.7% in Japanese vs. 54.0% in Caucasians, p <
      0.001; A1 allele: 97.8% vs. 73.4%, p < 0.001). The frequency of A1 heterozygotes
      tended to be higher in Japanese alcoholics with fibrosis, compared with those
      without fibrosis (14.9% vs. 2.9%). Furthermore, within the fibrotic groups,
      cumulative alcohol intake was significantly lower in A1 heterozygotes than in the
      A1 homozygotes (877 +/- 118 kg vs. 1369 +/- 90 kg,p < 0.05). In conclusion, a
      genetic polymorphism in the IL1-Ra gene may influence the risk of developing
      hepatic fibrosis in Japanese alcoholics. The same study should be conducted in
      Caucasian patients having more frequency of IL1-Ra A1 heterozygotes.

PMID- 9622393
TI  - Immunohistochemical detection of 4-hydroxy-2-nonenal-modified-protein adducts in
      human alcoholic liver diseases.
AB  - 4-Hydroxy-2-nonenal (HNE) is one of the major components of lipid peroxidation
      product and has been shown to react with proteins to form HNE-protein adducts.
      HNE-protein adducts are relatively stable and can be used as a marker of radical
      mediated cellular damage. We report herein the immunohistochemical analysis of
      HNE-protein adducts in human alcoholic liver diseases using a specific monoclonal
      antibody HNEJ-2. Cytoplasm of hepatocytes and bile duct epithelia was positively
      stained for HNE-protein adducts, and the nucleus was negligibly stained. The
      immunohistochemical intensity of hepatocytes was classified into three groups:
      strong, moderate, and faint staining. Strong staining was found in 43% of
      alcoholic liver diseases and in 4% of viral liver diseases. Hepatocytes of
      alcoholic liver diseases contained a higher amount of HNE-protein adducts than
      those of viral liver diseases, and the difference was statistically significant
      (p = 0.005; chi2 test). Semiquantitative analysis of the histological intensities
      of HNE-protein adducts and iron indicated a significant positive correlation (p =
      0.084; Spearman's rank correlation). The localization of HNE-protein adducts and
      iron in hepatocytes appeared to be identical. These data suggested the
      correlation between HNE-protein adducts and iron. Our results indicate that HNE
      protein adducts, a marker of oxidative stress-induced damage, are increased in
      human alcoholic liver damage, and that hepatic siderosis may act on the
      production of free radicals.

PMID- 9622394
TI  - An enzyme immune assay for serum anti-acetaldehyde adduct antibody using low
      density lipoprotein adduct and its significance in alcoholic liver injury.
AB  - An acetaldehyde (AcH) adduct was prepared using rabbit low-density lipoprotein as
      carrier proteins. An antibody against this adduct was raised in Watanabe
      heritable hyperlipidemic rabbits and cross-reacted with human low-density
      lipoprotein and bovine serum albumin adducts. Using this antibody, serum anti-AcH
      adduct antibody levels were measured by a direct ELISA method in 56 Japanese
      adults (healthy adults and patients with nonalcoholic gastrointestinal diseases,
      alcoholic liver injury, or alcoholic pancreatitis). The antibody level (mean +/-
      SD) was 22 +/- 10 microg/ml in healthy adults, 22 +/- 11 microg/ml in
      nonalcoholic gastrointestinal diseases, and 16 +/- 13 microg/ml in alcoholic
      pancreatitis. These antibody levels tended to increase with the progression of
      alcoholic liver injury, starting from fatty liver via hepatitis to cirrhosis, 29
      +/- 24 microg/ml in fatty liver, 35 +/- 29 microg/ml in alcoholic hepatitis, and
      46 +/- 54 microg/ml in alcoholic cirrhosis. The antibody level in patients taking
      100 g or more of ethanol per day tended to be higher, compared with those in
      people taking less ethanol. A follow-up observation revealed that alcohol
      abstinence after hospitalization raised serum anti-AcH-adduct antibody level in
      some patients and kept it constantly low in other patients. The
      immunohistochemical study using the anti-AcH-adduct antibody revealed the
      presence of adduct-like substance in hepatocytes of liver biopsy specimens
      obtained from patients with alcoholic liver disease. The results indicate that
      the anti-AcH-adduct antibody may be associated with the progress of alcoholic
      liver diseases.

PMID- 9622395
TI  - Hepatitis G virus infection in patients with alcoholic liver disease.
AB  - The recently discovered hepatitis G virus (HGV) is believed to be a single
      stranded RNA virus belonging to the Flaviviridae family, similar to hepatitis C
      virus (HCV), but much remains to be learned about its characteristics and
      clinical manifestations. Although it has been suggested that alcohol intake might
      have an effect on liver pathology by promoting the proliferation of HCV, the
      association between HGV infection and alcohol intake is yet to be elucidated. In
      the present study, we investigated the prevalence of HGV-RNA and HCV-RNA in 63
      patients with alcoholic liver disease, and studied the effects of alcohol on the
      progression of hepatic damage in HGV-RNA positive patients. Among these 63
      patients, 9 (14%) were HGV-RNA-positive and 37 (59%) were HCV-RNA-positive. Seven
      (78%) of the nine HGV-RNA positive patients were also infected with HCV. The
      patients showed no significant differences of clinical features in relation to
      the presence or absence of HGV infection. There were also no differences of liver
      histology among HCV-RNA-positive patients with or without HGV-RNA. The two
      patients infected with HGV alone had alcoholic hepatitis and nonspecific reactive
      hepatitis, respectively. In this study, alcohol seemed to have little influence
      on the progression of the liver histology in HGV-RNA-positive patients.

PMID- 9622396
TI  - Some sociocultural observations on alcohol-related problems in Japan.

PMID- 9622397
TI  - Alcohol-related problems in Taiwan with particular emphasis on alcoholic liver
      diseases.
AB  - Socioeconomic development has led to a progressive increase of alcohol
      consumption in Taiwan, with an accompanying increase in alcohol-related
      psychiatric problems, traffic accidents, and liver disease. The prevalent rates
      of alcohol dependence for Han Chinese and Fomosan aborigines were 0.1% and 1%,
      respectively in 1950. The rate of alcohol dependence increased to 23% for
      aborigines in 1995. The number of cases of death and serious injuries due to
      alcohol-related traffic accident has decreased, and the number of fatalities
      resulting from these accidents has decreased from third to eighth since the
      inception of a program of random traffic stops with alcohol breath test in 1997.
      Alcohol liver disease (ALD) was defined as daily alcohol consumption of 60 g, for
      a duration of longer than 5 years. We classified ALD patients into two groups:
      (1) those whose average daily consumption of alcohol exceeded 120 g for a
      duration longer than 15 years (group A); and (2) all other patients (group B).
      The case records of 33 cases of biopsy-confirmed ALD were obtained for study. The
      average of daily alcohol consumption in these cases was 160 g. All but one of
      these patients were male, age ranged from 26 to 69 years, with an average of
      43.1. Clinically, ill-defined gastrointestinal symptoms were the most common
      presentation (61%), and hepatomegaly was the main physical sign (73%). The
      average mean corpuscular volume values of ALD and non-ALD patients were 102.3 +/-
      10.94 and 94.5 +/- 8.1, respectively (p < 0.01). The mean corpuscular volume
      values of group A and group B were 102.9 +/- 9.7 vs. 96.5 +/- 9.11 (p < 0.05).
      Result from serum SGOT/SGPT and gamma-glutamyltransferase/alkaline phosphatase
      for ALD and non-ALD revealed statistically significant differences between these
      groups. Using the avidin-biotin complex technique, tissue IgA deposition for ALD
      patients was found to be different from that of non-ALD patients. Ten of 13 ALD
      patients vs. 2 of 13 non-ALD patients had continuous-form IgA deposition.
      Histologically, 45.5% of ALD patients had alcoholic cirrhosis, whereas alcoholic
      hepatitis was present in only 9.1% of patients. Overall, 88% of cases showed
      various severity of fatty metamorphosis.

PMID- 9622398
TI  - Korean status of alcoholics and alcohol-related health problems.
AB  - Recent changes in the socioeconomic status of Korea have caused big differences
      in alcohol-related social and health problems. The traditional trait of drinking
      mild fermented beverages with nutritional side dishes and meals has shifted to
      drinking strongly distilled liquors without any side dishes. Moreover, the
      alcohol consumption per adult capita of Korea is now 8.1 liters, which parallels
      the level of other developed countries; it used to be 1.0 liter in 1960 and 7.0
      liters in 1980, respectively. But the alcohol consumption per capita of adult
      males is now 18.4 liters. Consequently, the national incidence of alcohol-related
      diseases and accidents has rapidly increased. Korean adult males have the highest
      risk of the incidence of hepatoma. The rate of car accidents caused by drunken
      driving is about 10-fold higher than in any other developed country.

PMID- 9622399
TI  - Alcohol-related harm in Australia: current issues and future prospects.

PMID- 9622400
TI  - Current problems of alcohol abuse in the Western Pacific Region and future
      prospects.

PMID- 9622401
TI  - Validation of a predictive model for postoperative pulmonary complications.
AB  - OBJECTIVE: To test or validate a previously reported model for predicting
      postoperative pulmonary complications (PPCs) after elective abdominal surgical
      procedures. DESIGN: Prospective, descriptive. SETTING: Four midwestern hospitals
      serving a diverse population of patients. PATIENTS: Two hundred seventy-six adult
      patients who had undergone abdominal surgery (51% men, 49% women; mean age 54.1
      +/- 5.3 years). OUTCOME MEASURES: PPC developed in 26.4%. DATA COLLECTION: Data
      were collected preoperatively during a brief interview and a pulmonary physical
      examination and on the first 6 postoperative days. RESULTS: A six risk-factor
      model was tested in this sample of subjects. The model validated relatively well
      in the sample of 276 subjects with use of the basic criteria of correct
      classification, sensitivity, and specificity. However, when a new model was
      developed from this sample, differing risk factors emerged as significant
      independent predictors. CONCLUSIONS: Further research is needed to assess the
      stability of the risk factors and test the models in differing settings and
      populations of patients.

PMID- 9622402
TI  - Development and testing of the modified version of the pulmonary functional
      status and dyspnea questionnaire (PFSDQ-M).
AB  - OBJECTIVE: Describe the process of development and testing to reduce the
      Pulmonary Functional Status and Dyspnea Questionnaire (PFSDQ) from 164 items to a
      modified questionnaire (the PFSDQ-M) consisting of 40 items. DESIGN: Instrument
      development and testing for reliability, validity, and practicality. SETTING:
      Hospital-based outpatients. PATIENTS: Testing was done on three groups of
      clinically stable patients with chronic obstructive pulmonary disease: a
      secondary analysis of 131 subjects for item selection, reliability, and validity;
      50 additional subjects evaluating the PFSDQ-M for internal consistency, test
      retest correlations, and construct validity; and 34 subjects from a longitudinal
      study for responsiveness. OUTCOME MEASURES: PFSDQ, PFSDQ-M, and spirometry.
      RESULTS: The practicality of the PFSDQ-M was supported by its sixth- to seventh
      grade reading level, ease of reading (Flesch-Kincaid 69.5), self-administration,
      brief period for testing (7 minutes initially, 6 minutes on repeated testing),
      and limited missing data (< 8%). Reliability of the three components was
      supported by internal consistency alpha = 0.93 for change experienced by the
      patient with activities (CA), 0.95 for dyspnea with activities (DA), and 0.95 for
      fatigue with activities (FA). Good stability of the PFSDQ-M was demonstrated on
      test-retest; r = 0.70 for change, 0.83 for dyspnea, and 0.79 for fatigue (with
      activities). The usefulness of the PFSDQ-M in discriminating between dyspnea
      scores in patients based on their rate of deterioration in lung function was
      demonstrated. CONCLUSIONS: The PFSDQ was modified by reducing the number of
      activities evaluated, standardizing scaling formats, and adding a fatigue
      component. Findings suggest that the PFSDQ-M demonstrates initial reliability;
      good validity estimates, as seen with the factor analysis, and the dyspnea and
      activity scores appear responsive to physiologic changes in lung function over
      time.

PMID- 9622403
TI  - Effectiveness of a music therapy intervention on relaxation and anxiety for
      patients receiving ventilatory assistance.
AB  - OBJECTIVE: To test the effects of music therapy on relaxation and anxiety
      reduction for patients receiving ventilatory assistance. DESIGN: Two-group,
      pretest-posttest experimental design with repeated measures. Subjects randomized
      to either a 30-minute music condition or a rest period. SETTING: Four urban
      midwestern intensive care units. SUBJECTS: Fifty-four alert, nonsedated patients
      receiving mechanical ventilation. OUTCOME MEASURES: State anxiety (pretest and
      posttest), heart rate, and respiratory rate obtained every 5 minutes for 30
      minutes. RESULTS: Subjects who received music therapy reported significantly less
      anxiety posttest (10.1) than those subjects in the control group (16.2). Heart
      rate and respiratory rate decreased over time for those subjects in the music
      group as compared with the control group subjects. CONCLUSIONS: A single music
      therapy session was found to be effective for decreasing anxiety and promoting
      relaxation, as indicated by decreases in heart rate and respiratory rate over the
      intervention period with this sample of patients receiving ventilatory
      assistance.

PMID- 9622404
TI  - Patient perception of fatigue while undergoing long-term mechanical ventilation:
      incidence and associated factors.
AB  - OBJECTIVE: To describe a chronically critically ill population of patients
      receiving long-term ventilatory assistance, including patient perception of
      fatigue and the associated factors of nutritional status, depression, and sleep
      rest. DESIGN: Prospective, descriptive correlational design. SETTING: Two
      tertiary care, university-affiliated medical centers. SUBJECTS: Twenty subjects
      who were undergoing mechanical ventilation for at least 7 days and who were in
      the process of weaning. RESULTS: Descriptive, correlational, and t test
      statistics were used in the data analysis. There was a 100% prevalence rate of
      fatigue, and with a 10-cm visual analogue scale, 45% of the subjects rated their
      fatigue as severe (> or = 6.0 cm) in intensity. The sample's mean serum albumin
      was 2.7 gm/dl, and mean hemoglobin was 10.1 gm/dl, but there were no
      statistically significant relationships between fatigue and nutritional status.
      Subjects' depression scores were in the moderate range, and they evaluated their
      sleep as fragmented and only moderately effective. Fatigue and depression were
      strongly correlated (r = 0.61; p = 0.004); there were no statistically
      significant relationships between fatigue and the sleep-rest scales. CONCLUSIONS:
      The descriptive findings suggest that patients receiving long-term ventilatory
      assistance are undernourished and experience fatigue, depressed mood state, and
      disruptions of their sleep-rest patterns.

PMID- 9622405
TI  - Long-term chest wall discomfort in women after coronary artery bypass grafting.
AB  - OBJECTIVE: The purpose of the study was to determine the occurrence of long-term
      chest wall discomfort in women after coronary artery bypass grafting. DESIGN:
      Prospective repeated-measures design. SETTING: Posthospitalization. SAMPLE: Fifty
      one women who had undergone coronary artery bypass grafting. Data were collected
      at 12 and 18 months by self-report and data collection instruments. INSTRUMENTS:
      Life Orientation Test, Satisfaction with Life Scale, Profile of Mood States,
      Sickness Impact Profile, interview schedule, and discomfort scale 0 to 10.
      RESULTS: Women who had an internal mammary artery graft had significantly (p =
      0.003) more discomfort. Most discomforts were intermittent and did not interfere
      with daily activities. However, the feelings of numbness and itchiness tended to
      be continuous.

PMID- 9622406
TI  - Assessment of quality of life with the Nottingham Health Profile among women with
      coronary artery disease.
AB  - OBJECTIVE: To examine the differences in the health-related quality of life
      (HRQOL) of Finnish women with coronary artery disease (CAD) (n = 91) in
      comparison with Finnish men with CAD (n = 189). Healthy women (n = 990) served as
      a control group. DESIGN: Prospective, cross-sectional survey. SETTING: Surgical
      and medical clinics at the University of Oulu, Finland. PATIENTS: Twenty-one
      women underwent coronary artery bypass grafting (CABG), 40 women underwent
      percutaneous transluminal coronary angioplasty (PTCA), and 30 women received
      medication for treatment of CAD. The patients in the medication group were taking
      beta blockers (81%), long-acting nitrates (86%), calcium channel blockers (43%),
      aspirin (79%), and lipid-lowering drugs (18%). OUTCOME MEASURES: The Nottingham
      Health Profile (NHP), which consists of six dimensions: energy, sleep, pain,
      emotional reactions, social isolation, and physical mobility. Higher mean indexes
      signify lower HRQOL. INTERVENTION: The patients referred to CABG and PTCA
      procedures were interviewed and asked to fill in the questionnaire on the day
      before the operation. They were instructed to describe their HRQOL over the
      preceding 3 months. The patients in the medication group were mailed the NHP
      questionnaire. RESULTS: Women with CAD reported significantly poorer HRQOL than
      age-matched women in the healthy sample, as measured by the following dimensions
      of the NHP: energy, sleep, pain, emotional reactions, and physical mobility. This
      indicates the NHP dimensions affected by CAD among women. HRQOL for women with
      CAD was lower than that of men with CAD. The mean indexes of four of the six NHP
      dimensions, energy, sleep, emotional reactions, and physical mobility were higher
      for women with CAD than men with CAD in the two youngest age groups. Social
      isolation was most common in the youngest age group among both women and men with
      CAD. In women with CAD, emotional reactions and social isolation were most
      clearly related to demographic characteristics such as traumatic life
      experiences, depression, financial situation, and smoking. CONCLUSIONS: These
      findings suggest that the subjective HRQOL should be considered along with the
      clinical severity of the disease in the evaluation of CAD. The findings further
      shed light on the HRQOL of especially young women with CAD, the female and male
      patients' referral for treatment, and the use of the NHP instrument among
      patients with CAD.

PMID- 9622407
TI  - A comparison of intravascular pressure monitoring system contamination and
      patient bacteremia with use of 48- and 72-hour system change intervals.
AB  - OBJECTIVE: To determine the incidence of culture positivity in intravascular
      monitoring systems by comparing 48- versus 72-hour intervals for flush solution,
      stopcocks, and catheters on removal. DESIGN: Prospective, quasi-experimental,
      random assignment. SETTING: Intensive care units of a midwestern university
      medical center and a community hospital. PATIENTS: Seventy-six critically ill
      adult patients, ranging in age from 24 to 96 years (X = 61.6), requiring arterial
      or pulmonary artery catheters. OUTCOME MEASURE: Culture positivity of flush
      solution, stopcocks, or catheter tips. INTERVENTION: Data collection was
      initiated at designated change intervals of 48- or 72-hours; cultures were taken
      of flush solution and stopcocks; catheter tip cultures were obtained on catheter
      removal. RESULTS: Chi-square analyses indicated that increasing the change
      interval to 72 hours resulted in no significant difference in culture positivity
      of catheter tips. However, the difference between the 48- and 72-hour groups in
      culture-positivity rates of stopcocks from arterial catheters was significant (1,
      N = 82) = 6.86, p less than 0.01. CONCLUSIONS: Our results showed that increasing
      the change interval to 72 hours did not increase the risk of catheter-associated
      infection or catheter-associated bacteremia. Chi-square analysis did not show an
      association between culture-positive stopcocks, the incidence of culture-positive
      catheter tips, entries into the system, or catheter-related bacteremia and a
      change interval that was increased to 72 hours. Thus, increasing the change
      interval to 72 hours does not increase the risk of infection.

PMID- 9622408
TI  - Herpes simplex encephalitis: a review.
AB  - Patients with herpes simplex encephalitis generally have altered mental function
      and are rarely able to provide a good medical history. Failure to diagnose this
      serious disease may result in permanent neurologic damage or death of the
      patient. Rapid institution of newer diagnostic tests such as polymerase chain
      reaction for herpes simplex virus is essential for proper diagnosis. Parenteral
      acyclovir therapy is efficacious but, clearly, improvements in prevention and
      therapy are still important research goals. This review is meant to inform
      physicians and nurses concerning the current diagnosis and management of this
      treatable but potentially fatal illness.

PMID- 9622409
TI  - Reverse ventriculophasic effect.

PMID- 9622410
TI  - Role of nitric oxide in the biology, physiology and pathophysiology of
      reproduction.
AB  - Following its benchmark discovery, nitric oxide (NO) is now known to play
      important functional roles in a variety of physiological systems. Within the
      vasculature, NO induces vasodilation, inhibits platelet aggregation, prevents
      neutrophil/platelet adhesion to endothelial cells, inhibits smooth muscle cell
      proliferation and migration, regulates programmed cell death (apoptosis) and
      maintains endothelial cell barrier function. NO generated by neurons acts as a
      neurotransmitter, whereas NO generated by macrophages in response to invading
      microbes acts as an antimicrobial agent. Because neurons, blood vessels and cells
      of the immune system are integral parts of the reproductive organs, and in view
      of the important functional role that NO plays in those systems, it is likely
      that NO is an important regulator of the biology and physiology of the
      reproductive system. Indeed, in the past 10 years, NO has established itself as a
      polyvalent molecule which plays a decisive role in regulating multiple functions
      within the female as well as the male reproductive system. This review provides
      an overview of the role of NO in various reproductive organs under physiological
      and pathological conditions.

PMID- 9622411
TI  - The nitric oxide pathway in pre-eclampsia: pathophysiological implications.
AB  - Pre-eclampsia, one of the most significant health problems in human pregnancy,
      complicates approximately 6-8% of all gestations and is the leading cause of
      fetal growth retardation, infant morbidity and mortality, premature birth and
      maternal death. Recent research implicates free radicals in the pathophysiology
      of pre-eclampsia. This review covers the biochemistry of nitric oxide (NO) and
      possible interactions with other free radicals. Studies in the rat show that
      pregnancy is associated with enhanced production and responsiveness to NO in both
      reproductive tissues and blood vessels. Rats infused with NG-nitro-L-arginine
      methyl ester (L-NAME, a NO synthase inhibitor) have been used as an animal model
      of pre-eclampsia, and the effects of steroid hormones on blood pressure in this
      model have been tested. Results suggest that pre-eclampsia may be a state of NO
      deficiency. However, in humans there seem to be contradictions regarding the
      involvement of NO in maternal adaptation to pregnancy. It is suggested that NO
      may be one of several systems that act in concert to maintain a symbiotic
      relationship between mother and fetus. However, the input of each system may be
      genetically determined.

PMID- 9622412
TI  - Intracytoplasmic sperm injection: a state of the art technique.
AB  - Of the micromanipulation techniques developed in the twentieth century,
      intracytoplasmic sperm injection (ICSI) has been the major breakthrough in the
      field of assisted fertilization. This article reviews the indications for the use
      of ICSI, its clinical application, the establishment of an ICSI programme
      including protocol and the results obtained since the introduction of ICSI and
      the potential risks. In addition, intracytoplasmic spermatid injection is briefly
      discussed.

PMID- 9622413
TI  - Studies of percutaneous epididymal sperm aspiration (PESA) and intracytoplasmic
      sperm injection.
AB  - Four distinct studies were carried out using two data sets of percutaneous
      epididymal sperm aspiration (PESA) and intracytoplasmic sperm injection (ICSI)
      procedures performed from March 1993 to January 1997. In study A, an analysis of
      181 ICSI treatment cycles following PESA revealed a successful epididymal sperm
      retrieval rate of 83%. It confirmed that PESA is an effective sperm retrieval
      method and the associated ICSI pregnancy rate (35% per embryo transfer) compared
      favourably with that of other sperm retrieval methods. In study B, the relevance
      of a prior diagnostic PESA procedure was ascertained by comparing the sperm
      retrieval rates in two groups of patients having their first ICSI treatment cycle
      with spermatozoa retrieved through PESA. Group B1 (n = 50) had diagnostic PESA
      prior to the ICSI treatment cycle PESA procedure, unlike patients in group B2 (n
      = 64) who did not. The sperm retrieval rate in the treatment cycle procedure was
      not different at 90 and 82.8% for groups B1 and B2 respectively. However, the
      discontinuation of diagnostic PESA is fraught with problems including liability
      to medico-legal sanctions. In study C, analysis of 177 treatment cycles involving
      PESA and ICSI revealed a successful sperm retrieval rate by PESA of 82% in the
      first cycle, 93% in the second, 96% in the third and 100% in the fourth cycle.
      The same trend was evident when sperm retrieval was examined in relation to each
      of the epididymides. Retrieved spermatozoa were found to be motile in 67-100% of
      cases and the frequency of samples containing motile spermatozoa did not decrease
      with increase in the number of PESA attempts. These results show that PESA does
      not jeopardize future epididymal sperm retrieval. In study D, the outcome of
      treatment with ICSI using ejaculated spermatozoa (305 cycles) (group D1) was
      compared with that of ICSI using spermatozoa obtained through PESA (54 cycles)
      (group D2). The median age of women in the two groups of couples was similar (34
      years). In group D1, 70% of metaphase II oocytes were fertilized compared with
      61% in group D2 (P < 0.01). The cleavage rate and the median numbers of
      transferred and cryopreserved embryos were similar in both groups. There was no
      significant difference between the clinical pregnancy rates (33 and 42% in groups
      D1 and D2 respectively). Our results show that the outcome of PESA-ICSI treatment
      compares favourably with that of ICSI using ejaculated spermatozoa.

PMID- 9622414
TI  - Predictive value of normal sperm morphology: a structured literature review.
AB  - The aim of the study was to conduct a structured review of the literature
      published on the use of normal sperm morphology, as an indicator of male
      fertility potential in the in-vitro fertilization (IVF) situation, and to
      establish the universal predictive value of this semen parameter. Published
      literature in which normal sperm morphology was used to predict fertilization and
      pregnancy, during the period 1978-1996, was reviewed. A total of 216 articles
      were identified by the sourcing methodology, but only 49 provided data that could
      be tabulated and analysed. Of these, only 18 provided sufficient data for
      statistical analysis. Fifteen studies used the strict criteria to evaluate sperm
      morphology, two used World Health Organization (WHO) guidelines and one used both
      the strict criteria and the WHO guidelines. All the studies (n = 10) using the 5
      and 14% normal sperm morphology thresholds (strict criteria) produced positive
      predictive values for IVF success. In the prediction of pregnancy, 82% (9/11) and
      75% (6/8) of the studies produced positive predictive values when using the 5%
      and 14% thresholds respectively. Aggregating the data produced around the 5%
      normal sperm morphology threshold (strict criteria), the overall fertilization
      rates were 59.3% (1979/3337; per oocyte) for the < or = 4% group and 77.6%
      (10345/13327; per oocyte) for the >4% group, and the overall pregnancy rates were
      15.2% (60/395; per cycle) and 26.0% (355/1368; per cycle) respectively. The no
      transfer rates across the 5% threshold were 24.0% (86/359; per cycle) in the < or
      = 4% group compared to 7.4% (80/1088; per cycle) in the >4% group. The inclusion
      of an accurately evaluated normal sperm morphology count as an integral part of
      the standard semen analysis makes this analysis still the most cost-effective
      means of evaluating the male factor.

PMID- 9622415
TI  - Revisiting gonadotrophin-releasing hormone agonist protocols and management of
      poor ovarian responses to gonadotrophins.
AB  - Within the past decade, gonadotrophin-releasing hormone (GnRH) agonists have
      contributed greatly to the success of cycles programmed for in-vitro
      fertilization and embryo transfer. However, apart from a preventive effect on the
      luteinizing hormone (LH) surge, most of the beneficial effects of these molecules
      are still only partly known. A precise analysis of regimens using GnRH agonists
      for ovarian stimulation shows that many parameters may interfere with the outcome
      of long-term and short-term protocols. The great variability between these
      protocols hampers our comprehension of the mechanisms involved in the overall
      clinical improvement seen with this therapy. The hypophyseal desensitization
      induced by GnRH agonists is greatly dependent on the dose and duration of their
      administration, but the residual gonadotrophin secretion is imperfectly estimated
      by hormonal measurements using radioimmunometric assays. Moreover, the specific
      role of GnRH agonist-induced ovarian quiescence on subsequent ovarian
      responsiveness to gonadotrophins and on endometrial receptivity deserves further
      investigation. Finally, a direct ovarian action of GnRH agonists on
      steroidogenesis, folliculogenesis and embryo quality is still controversial in
      humans. These putative deleterious effects of GnRH agonists have led some authors
      to recommend a reduction of both dose and duration of GnRH agonist administration
      for women identified by a poor response to gonadotrophins. Using this approach, a
      few reports have recently shown some clinical advantages for ovarian
      responsiveness but no convincing evidence for any improvement in pregnancy rate.
      It thus appears that the overall impact of GnRH agonists on reproductive function
      is still partly misunderstood.

PMID- 9622416
TI  - Peroneus brevis tendon tears: pathophysiology, surgical reconstruction, and
      clinical results.
AB  - Chronic peroneus brevis tendon tears are frequently overlooked or misdiagnosed.
      They are a more common problem than previously noted. Twenty patients were
      reviewed in the largest clinical series of its kind. The most reliable diagnostic
      sign was persistent swelling along the peroneal tendon sheath. The
      pathophysiologic mechanism is subclinical, or overt, subluxation of the tendon
      over the posterolateral edge of the fibula. This produces multiple longitudinal
      splits. Treatment is primarily surgical and must address both the split tendon
      and the subluxation that caused it. A new classification that guides surgical
      treatment is proposed. Debridement and repair are recommended for grade 1
      tendons, which have damage to less than 50% of the cross-sectional area. Excision
      of the damaged segment and tenodesis to the peroneus longus are recommended for
      grade 2 tendons, which have destruction of greater than 50% of the cross
      sectional area. Both methods must be augmented by stabilization of the etiologic
      subluxation. The average postoperative AOFAS score was 85. Return to maximum
      function is prolonged, but good-to-excellent results were found in the majority
      of patients.

PMID- 9622417
TI  - Peroneal tendon injuries.
AB  - Injury to the peroneal tendons is a frequently overlooked cause of persistent
      lateral ankle pain after trauma. Peroneal tendon anatomy, biomechanics,
      diagnostic studies, and traumatic disorders were reviewed.

PMID- 9622418
TI  - The medial collateral ligaments of the human ankle joint: anatomical variations.
AB  - This study aimed to investigate anatomical variations within the medial
      collateral ligament complex of the human ankle joint. Osteoligamentous
      preparations of 40 ankles from 20 cadavers were studied. Six different component
      bands of the medial collateral ligament complex were observed: four superficial
      bands (tibiospring, tibionavicular, superficial posterior tibiotalar, and
      tibiocalcaneal ligaments), of which only the tibiospring and tibionavicular
      ligaments were constant, and two deep bands (deep posterior tibiotalar and deep
      anterior tibiotalar ligaments), of which only the deep posterior tibiotalar
      ligament was constant. No pattern was observed in the distribution of additional
      bands. A consistent and universally accepted system for naming the various bands
      of the medial collateral ligament is necessary to enable easy and accurate
      comparisons between studies. We suggest that this system should be based on the
      attachments of the ligaments.

PMID- 9622420
TI  - Treatment of superficial and deep peroneal neuromas by resection and
      translocation of the nerves into the anterolateral compartment.
AB  - An approach to the treatment of dorsal foot pain of neuroma origin is described
      based upon principals demonstrated to be effective in the treatment of upper
      extremity dorsoradial neuromas: translocation of the appropriate nerves into a
      muscle environment away from the joint. In the lower extremity, this requires
      identification of the appropriate nerves by anesthetic block, resection of the
      dorsal foot neuroma(s), and translocation of the nerves into the muscles of the
      anterolateral compartment. This approach yielded excellent results in 9 of the 11
      patients with a mean follow-up of 29 months.

PMID- 9622419
TI  - Mechanical comparison of biplanar proximal closing wedge osteotomy with plantar
      plate fixation versus crescentic osteotomy with screw fixation for the correction
      of metatarsus primus varus.
AB  - Proximal crescentic metatarsal osteotomy is a clinically successful technique for
      correcting metatarsus primus varus in hallux valgus surgery. However, there have
      been instances of dorsal elevation of the metatarsal head with this technique.
      Mechanical testing on 10 matched pairs of cadaver feet was performed to evaluate
      a new technique combining a biplanar closing wedge osteotomy and plantar plate
      fixation versus crescentic metatarsal osteotomy. The specimens were tested in
      cantilever-bending mode on an MTS Mini Bionix test frame. The mean load-to
      failure values were 127.2 +/- 81.9 N (SD) for biplanar osteotomy with plate
      fixation and 44.9 +/- 43.3 N for crescentic osteotomy (P = 0.019); the mean
      stiffness values at the initial portion of the load-deflection curve were 83.11
      +/- 73.76 N/mm and 31.95 +/- 43.00 N/mm, respectively (P = 0.012). The biplanar
      wedge osteotomy with plantar plate fixation demonstrated significantly stronger
      fixation than the crescentic osteotomy, with higher mean load-to-failure and
      stiffness values. This newly described technique may provide an acceptable
      alternative for patients at risk for dorsal elevation of the metatarsal,
      particularly those who are noncompliant or have osteopenia. Clinical study will
      determine whether this new technique offers satisfactory long-term results.

PMID- 9622421
TI  - Cost-effectiveness comparison of three methods of internal fixation for
      arthrodesis of the first metatarsophalangeal joint.
AB  - We used decision-analysis modeling to determine the most cost-effective fixation
      device among Herbert screws, AO screws, and the Luhr plate for first
      metatarsophalangeal joint arthrodesis. The model considered patient-reported
      outcomes at minimum 2-year follow-up, patient charges for the entire course of
      care, and event and outcome incidences within each fixation group. AO screws had
      the lowest average cost of utility and, therefore, are the most cost-effective
      fixation device for first metatarsophalangeal joint arthrodesis even though
      utility is highest with the Luhr plate. Operating room costs and union rate most
      strongly influenced cost-effectiveness.

PMID- 9622422
TI  - Intratendinous alterations as imaged by ultrasound and contrast medium-enhanced
      magnetic resonance in chronic achillodynia.
AB  - OBJECTIVES: We performed a comparative study of ultrasonography and gadolinium
      imaging contrast-enhanced T1-weighted magnetic resonance to evaluate tendon
      pathology in chronic Achilles tendon disorder. Another main issue was to evaluate
      the structural basis as defined by histopathology from hypoechoic compared with
      normoechoic areas within the same tendon. MATERIALS AND METHODS: Twenty patients
      (16 male, 4 females, median age 40 years) with chronic achillodynia participated
      in the study. Clinical examination revealed swelling and tenderness localized to
      the midportion of the Achilles tendon. Contrast medium-enhanced magnetic
      resonance imaging (CME-MRI) was performed in all patients. Ultrasonography-guided
      core biopsies were taken from regions with a clear widening of the tendon and a
      pathologic low-echo signal as well as from normoechoic areas. The specimens were
      analyzed with a standardized protocol giving a total tendon score (0-24), and a
      stereologic method for quantification of glycosaminoglycan (GAG)-rich areas.
      RESULTS: The volume of the intratendinous abnormality was larger in 13 of 20 when
      imaged by CME-MR (P < 0.05), whereas the shape and enlargement of the tendon per
      se were similarly imaged by ultrasound (US) and CME-MR. Tendon pathology as
      imaged by US was graded as severe from hypoechoic regions and moderate from
      normoechoic regions. The corresponding quantification of GAGs was 0.36 compared
      with 0.17, respectively (P < 0.001). CONCLUSION: CME-MR imaging revealed greater
      sensitivity in demonstrating intratendinous pathology than the ultrasound; this
      was documented by the larger size of the corresponding lesion and the fact that
      the pathology was occurring in areas that were considered normal by
      ultrasonography. US hypoechoic areas showed a markedly abnormal tendon structure
      including an increased amount of GAG-rich areas. However, moderate pathology was
      also found in the neighboring normoechogenous areas within the same tendon,
      indicating a more generalized disorder than depicted by echogenic properties.

PMID- 9622423
TI  - The fibular incisure of the tibia on CT scan: a cadaver study.
AB  - Twenty cadaver lower limbs were used for CT assessment of the fibular incisure of
      the tibia. The length of the syndesmotic facet is shorter in the anterior (11.20
      +/- 1.90 mm) than in the posterior (14.89 +/- 2.72 mm) (P < 0.001). The angle
      between anterior and posterior facets is 135.18 +/- 9.27 degrees. The depth of
      the fibular incisure of the tibia is 4.29 +/- 1.26 mm. The vertical distance of
      tibiofibular overlapping is 7.81 +/- 1.93 mm. The distance between anterior
      margin of the tibia and anterior margin of the fibula is 17.40 +/- 3.61 mm. The
      distance between the medial fibular border and the lateral border of the
      posterior tibia is 2.01 +/- 0.49 mm. The syndesmotic notch could be divided into
      two groups: significant concave surface and shallow concave surface. The position
      of the fibula in the incisural notch may depend on the depth of the fibular
      incisure of the tibia during traumatic forces applied on the syndesmosis. CT can
      display the tibial tubercles and clearly demonstrates the fibular incisure of the
      tibia and the interior of the tibiofibular space.

PMID- 9622424
TI  - A new modified technique for harvest of calcaneal bone grafts in surgery on the
      foot and ankle.
AB  - Reported sites for retrieval of cancellous bone for grafts include the iliac
      crest, greater trochanter, proximal tibia, and distal tibia. A new lateral
      technique for retrieval of cancellous bone from the calcaneus is evaluated
      through anatomic review, quantitative analysis, and retrospective clinical
      assessment. Of 22 patients managed with this technique over a 2-year period, 17
      returned for an evaluation by questionnaire, physical examination, and
      radiographic follow-up at an average of 7 months after surgery (range, 4-16
      months). Complaints/complications were minor: three had minor incisional
      symptoms, five had medial heel pain (3 caused by plantar fasciitis), and one had
      unchanged preoperative heel pain secondary to clubfoot deformity. Compared with
      more extensive bone-grafting procedures, this procedure offers the advantages of
      bone harvested under local anesthesia using a readily accessible ipsilateral
      extremity and producing minor complications.

PMID- 9622425
TI  - Verrucous carcinoma of the nail bed.
AB  - Verrucous carcinoma is a rare, highly keratinizing variant of squamous cell
      carcinoma of the skin or mucosae characterized by a local aggressiveness but a
      low potential for metastasis. The plantar form is also known as epithelioma
      cuniculatum. Fingers and toes are rarely affected, and tumors of the nail bed are
      exceptional. Clinically, the lesion presents like a wart and is then often
      misdiagnosed. Treatment of choice is wide surgical excision. A case of verrucous
      carcinoma of the nail apparatus is presented, and diagnosis is discussed.

PMID- 9622426
TI  - Congenital absence of the hallux fibular sesamoid: a case report and review of
      the literature.
AB  - Congenital absence of the fibular sesamoid of the hallux is an extremely rare
      condition. We could find only one previously reported case in the literature. The
      authors present a second case of congenital absence of the fibular sesamoid and a
      review of the literature regarding the clinical significance of this anomaly.

PMID- 9622427
TI  - Juvenile Tillaux fracture simulating syndesmosis separation: a case report.
AB  - The juvenile Tillaux fracture is an avulsion fracture (Salter-Harris type-3) of
      the anterolateral comer of the distal tibial epiphysis. We present a case in
      which the severely displaced Tillaux fragment became incarcerated between the
      distal tibia and fibula, simulating a syndesmotic separation radiographically. To
      our knowledge, such a fracture pattern as not been previously described.
      Preoperative computerized tomography provided accurate imaging of the unusual
      fracture pattern. Open extrication of the fracture fragment was followed by
      spontaneous reduction of the syndesmosis. The Tillaux fracture healed following
      open reduction with pin fixation, and the patient had an excellent functional and
      radiographic result at 2-year follow-up.

PMID- 9622428
TI  - External fixation for the treatment of Charcot arthropathy of the ankle: a case
      report.

PMID- 9622429
TI  - A new physical sign in arthroscopy of the ankle.

PMID- 9622430
TI  - Subtalar arthrodesis versus flexor digitorum longus tendon transfer for severe
      flatfoot deformity: an in vitro biomechanical analysis.

PMID- 9622431
TI  - Long-term reliability and validity of alcoholism diagnoses and symptoms in a
      large national telephone interview survey.
AB  - The long-term reliability and validity of telephone lay interview assessments of
      alcoholism were examined in the context of a large national community-based
      survey of over 8,000 male Vietnam era veterans. A subsample of 146 men was
      interviewed twice by telephone using the same structured interview an average of
      15 months apart to evaluate the long-term reliability of alcoholism symptoms and
      diagnoses. In addition, a search of Department of Veterans Affairs patient
      treatment files of inpatient hospitalizations between 1970 and 1993 yielded a
      subsample of 89 interviewed men with a past discharge diagnosis of alcohol
      dependence. The test-retest reliability of alcohol abuse and alcohol dependence
      diagnoses was good, with kappa coefficients of 0.74 and 0.61, respectively. The
      reliability of individual alcoholism symptoms was fair to good, with kappas of
      0.46 to 0.67. Ninety-six percent of individuals identified by Department of
      Veterans Affairs patient treatment files as having an alcohol dependence
      diagnosis were correctly diagnosed by the telephone interview. The results of the
      present study provide additional evidence for the long-term reliability and
      validity of lifetime alcoholism diagnoses, and suggest that the reliability and
      validity of telephone interview assessments of alcoholism are as good as that of
      an in-person interview. Telephone administration of structured psychiatric
      interviews appears to be an attractive alternative to in-person interviewing for
      gathering information about alcoholism and alcohol-related problems.

PMID- 9622432
TI  - Prediction of drinking outcomes for male alcoholics after 10 to 14 years.
AB  - This study reports on the long-term outcomes of 360 men who were hospitalized for
      alcoholism during 1980 to 1984 and followed at 12 months and again 10 to 14 years
      later. At the 10/14-year follow-up, 96 (26.7%) men were confirmed as deceased;
      255 (70.8%) men participated in the assessment/interview battery completed during
      baseline hospitalization. The battery consisted of psychosocial, alcohol-related,
      and psychiatric measures. Two distinct but highly correlated outcome measures
      were selected: a clinical rating scale and a factor score. Overall, predictors
      from baseline and 12-month follow-up included age at intake hospitalization,
      alcoholism severity, social stability, drinking days, and antisocial personality
      disorder. Approximately 37% of the assessed survivors were either totally
      abstinent or drinking nonabusively throughout the 10/14-year follow-up, whereas
      another 37% continued to drink abusively. Men who abstained or reduced alcohol
      intake reported better physical health at follow-up than those who continued to
      drink. Although our findings did not directly link alcoholism to death, they
      strongly indicate that chronic alcohol abuse may lead to premature death.

PMID- 9622433
TI  - Alveolar macrophage release of tumor necrosis factor-alpha in chronic alcoholics
      without liver disease.
AB  - Alcohol is an immunosuppressive drug, and chronic abuse has been associated with
      increased susceptibility to a variety of infections, including bacterial
      pneumonia and tuberculosis. Alveolar macrophages are the resident phagocytes of
      the lung and play a central role in lung host defenses against infection ranging
      from direct antibacterial activity to the release of proinflammatory cytokines
      such as tumor necrosis factor-alpha (TNFalpha). TNFalpha, in particular, plays a
      key role in the development of the early inflammatory response. In this study, we
      investigated the effects of chronic alcohol consumption on alveolar macrophage
      release of TNFalpha in vitro. We prospectively studied lipopolysaccharide (LPS)
      stimulated release of TNFalpha from alveolar macrophages obtained from
      bronchoalveolar lavage fluid (BALF) in 22 alcoholic (18 smokers, 4 nonsmokers)
      and 7 nondrinking healthy volunteers (3 smokers, 4 nonsmokers). The total number
      of cells recovered by bronchoalveolar lavage (BAL) and their differential
      distribution were not significantly different in alcoholics versus controls (43
      +/- 8 x 10(6) and 39 +/- 13 x 10(6), respectively). However, the total number of
      cells recovered from BALF was significantly higher in smokers (51 +/- 8 x 10(6))
      than in nonsmokers (19 +/- 5 x 10(6)). Spontaneous (basal) release of TNFalpha by
      alveolar macrophages was the same in alcoholics and controls. In contrast, LPS
      stimulated release of TNFalpha was significantly suppressed in alcoholics
      compared with that of controls (1343 +/- 271 vs. 3806 +/- 926 U TNF/ml/10(6)
      cells, respectively, p < 0.015). When controlled for smoking, LPS-stimulated
      TNFalpha production was suppressed in alcoholic nonsmokers (563 +/- 413 U
      TNF/ml/10(6)) compared with control nonsmokers (5113 +/- 1264 U TNF/ml/10(6)).
      LPS-stimulated TNFalpha production was also less in control smokers (2063 +/- 386
      U TNF/ml/10(6) cells) than in control nonsmokers (5113 +/- 1264 U TNF/ml/10(6)
      cells). There was no difference in TNFalpha production between smoking alcoholics
      and smoking control subjects. We conclude that chronic alcohol consumption
      significantly suppresses LPS-stimulated alveolar macrophage production of
      TNFalpha. This effect is obscured if the subject also smokes. Because TNFalpha
      production is an important element in host defense, this may explain, in part,
      the susceptibility of chronic alcohol abusers to a variety of infections.

PMID- 9622434
TI  - Combined efficacy of acamprosate and disulfiram in the treatment of alcoholism: a
      controlled study.
AB  - This study presents the results of a multicenter investigation of the efficacy of
      acamprosate in the treatment of patients with chronic or episodic alcohol
      dependence. One hundred eighteen patients were randomly assigned to either
      placebo or acamprosate, and both groups were stratified for concomitant voluntary
      use of disulfiram. Treatment lasted for 360 days, with an additional 360-day
      follow-up period. The primary efficacy parameters evaluated were: relapse rate
      and cumulative abstinence duration (CAD). Results were analyzed according to
      Intention-To-Treat principles using chi2, t, and multiple regression analyses
      where appropriate. After 30 days on study medication, 40 of 55 (73%) acamprosate
      treated patients were abstinent, compared with 26 of 55 (43%) placebo-treated
      patients (p = 0.019). The treatment advantage remained throughout the study
      medication period and was statistically significant until day 270 (p = 0.028).
      Twenty-seven percent of patients on acamprosate and 53% of patients on placebo
      had a first drink within the first 30 days of the study. The mean CAD was 137
      days (40% abstinent days) for the patients treated with acamprosate and 75 days
      (21% abstinent days) for the placebo group (p = 0.013). No adverse interaction
      between acamprosate and disulfiram occurred, and the subgroup who received both
      medications had a better outcome on CAD than the those on only one or no
      medication. Acamprosate was well tolerated. Diarrhea was the only significant
      treatment-induced effect. It was concluded that acamprosate was a useful and safe
      pharmacotherapy in the long-term treatment of alcoholism. Concomitant
      administration of disulfiram improved the effectiveness of acamprosate.

PMID- 9622435
TI  - Difficulties with questions on usual drinking and the measurement of alcohol
      consumption.
AB  - Questions about usual drinking play an important role in the construction of
      alcohol consumption measures. However, little is known about difficulties in
      answering these questions for respondents with variability in their drinking
      patterns. We investigated this in a community sample of 945 drinkers and in a
      clinical sample of 400 patients treated for alcohol and/or drug problems.
      Demographic variables were not consistently related to self-reported difficulty
      in answering, but a diagnosis of current DSM-IV alcohol dependence was
      significantly related in both samples. In modeling the relationship between
      alcohol consumption and DSM-IV alcohol dependence, the fit of the model to the
      data was significantly improved by the addition of a variable indicating
      respondents' difficulty answering the usual drinking questions. Using this
      information in the development of alcohol consumption questions may provide more
      precise estimates of the risk from alcohol consumption to outcomes such as
      alcohol dependence.

PMID- 9622436
TI  - Differential sensitivity to alcohol reinforcement in groups of men at risk for
      distinct alcoholism subtypes.
AB  - The present study examines the relationship of familial and personality risk
      factors for alcoholism to individual differences in sensitivity to the positively
      and negatively reinforcing properties of alcohol. Sixteen sons of male alcoholics
      with multigenerational family histories of alcoholism (MFH) and 11 men who self
      report heightened sensitivity to anxiety (HAS) were compared with 13 age-matched
      family history negative, low anxiety sensitive men (FH-LAS) on sober and alcohol
      intoxicated response patterns. We were interested in the effects of alcohol on
      specific psychophysiological indices of "stimulus reactivity," anxiety, and
      incentive reward. Alcohol significantly dampened heart rate reactivity to
      aversive stimulation for the MFH and HAS men equally, yet did not for the FH-LAS
      group. HAS men evidenced idiosyncrasies with respect to alcohol-induced changes
      in electrodermal reactivity to aversive stimulation (an index of anxiety/fear
      dampening), and MFH men demonstrated elevated alcohol-intoxicated resting heart
      rates (an index of psychostimulation) relative to the FH-LAS men. The results are
      interpreted as reflecting a sensitivity to the "stimulus reactivity-dampening"
      effects of alcohol in both high-risk groups, yet population-specific
      sensitivities to the fear-dampening and psychostimulant properties of alcohol in
      the HAS and MFH groups, respectively.

PMID- 9622437
TI  - Platelet monoamine oxidase activity in subgroups of alcoholics and controls:
      results from the Collaborative Study on the Genetics of Alcoholism.
AB  - OBJECTIVE: Platelet monoamine oxidase (MAO) B activity levels were evaluated to
      determine whether low platelet MAO activity is a marker for alcoholism,
      correlates of alcoholism (e.g., cigarette smoking), or a subtype of alcoholism.
      METHODS: Adult women (n = 788) and men (n = 685) participating in the
      Collaborative Study on the Genetics of Alcoholism study were evaluated with a
      semistructured interview, and blood samples were obtained for determination of
      platelet MAO activity using tryptamine (0.1 mM) as substrate. DSM-III-R alcohol
      dependent individuals were subgrouped using four currently available methods
      (e.g., two variations of the type 1/type 2 scheme, primary versus secondary
      typology, type A/type B dichotomy). RESULTS: In the overall sample, subjects'
      gender, cigarette smoking status, and the Collaborative Study on the Genetics of
      Alcoholism site at which their platelets were prepared explained 22% of the
      variance in platelet MAO activity levels, and multivariate analysis showed that
      carrying a broad diagnosis of alcohol dependence did not uniquely explain any
      additional variance in platelet MAO activity levels. Furthermore, within each of
      the alcoholic subgrouping methods tested, there were no significant differences
      in platelet MAO activity for type 1 versus type 2, type A versus type B, or
      primary versus secondary alcoholics. CONCLUSIONS: Cigarette smoking and male
      gender are associated with decreased platelet MAO activity levels. After
      considering these factors, a diagnosis of alcohol dependence does not predict any
      additional variance in MAO-B activity. Phenotypes of alcoholics (e.g., type 1
      versus type 2, type A versus type B, primary versus secondary) do not differ in
      platelet MAO activity. The results suggest that decreased platelet MAO activity
      is not a trait marker of alcoholism or one of its subtypes; but, rather, is a
      state marker of cigarette smoking.

PMID- 9622438
TI  - Selective acceleration of auditory processing in chronic alcoholics during
      abstinence.
AB  - Simultaneous auditory processing between the hemispheres was studied with a whole
      head magnetometer in 13 abstinent chronic alcoholics and 10 healthy control
      subjects. Auditory stimuli were presented monaurally with interstimulus intervals
      of 0.5 and 2.5 sec in different blocks. The N100m response, which contributes to
      stimulus detection, was significantly accelerated in the hemisphere ipsilateral
      to the ear stimulated in abstinent alcoholics. The MMNm response reflecting
      automatic stimulus-change detection peaked earlier in alcoholics, and the
      ipsilateral N100m latency correlated significantly with the abstinence duration.
      These results suggest that auditory processing is accelerated in the auditory
      cortex ipsilateral to the stimulated ear in chronic abstinent alcoholics and that
      the accelerated processing is at least partly reversible. This may be caused by
      the hyperexcitation in the brain related to the ethanol withdrawal.

PMID- 9622439
TI  - Preference for higher sugar concentrations and Tridimensional Personality
      Questionnaire scores in alcoholic and nonalcoholic men.
AB  - Animal studies have shown a positive association between the consumption of high
      concentrations of sweet solutions and subsequent alcohol intake. In a previous
      clinical study, it was shown that a preference for a high (0.83 M) concentration
      of sucrose (sweet liking) is characteristic of alcoholics, compared with
      controls. The present study was designed to determine whether personality
      variables, reported to be associated with subtypes of alcoholism, differentiate
      sweet liking alcoholics from sweet liking controls. Fifty-two male controls and
      26 alcoholic patients were tested for sweet preference and administered the
      Tridimensional Personality Questionnaire. Sweet liking alcoholics scored
      significantly higher on the Tridimensional Personality Questionnaire Novelty
      Seeking and Harm Avoidance scales and related subscales when compared with sweet
      liking controls. Further analysis showed that preferred sucrose concentration,
      Harm Avoidance score, and Novelty Seeking predicted alcoholic versus nonalcoholic
      group status at 65% sensitivity and 94% specificity, with a correct
      classification in 85% subjects. We hypothesize that sweet liking may identify a
      specific alcoholism subtype also characterized by high novelty seeking and high
      harm avoidance. These findings may have theoretical biological significance and
      practical clinical implications.

PMID- 9622440
TI  - Usefulness of carbohydrate-deficient transferrin in alcoholic patients with
      normal gamma-glutamyltranspeptidase.
AB  - The biological diagnosis of alcoholism is conducted routinely by assay of gamma
      glutamyltranspeptidase (GGT) and mean corpuscular volume (MCV). However, their
      low specificity and sensitivity have prompted research to find other more
      reliable parameters. Stibler showed an increase in desialylated transferrin
      [carbohydrate-deficient transferrin (CDT)] in alcoholic patients. The normal
      value of the serum CDT concentration is under 60 mg/liter; a value between 60 and
      100 mg/liter indicates probable alcoholism, and a value > 100 mg/liter indicates
      a very high probability of alcoholism (specificity: 99%). Its sensitivity ranges
      from 60 to 91%, and its specificity ranges from 92 to 100%. Its half-life is 17
      +/- 4 days. CDT is thus a useful laboratory marker, but its assay is costlier and
      more complex than that of GGT. This study concerns 31 alcohol-dependent patients
      as defined by DSM-IV, with GGT levels in the normal range. It evaluates CDT at
      day 0 and its time course after 15 days withdrawal. GGT and MCV were assayed
      concomitantly. Remarkably, the results show a sensitivity of 83.9 (26 positives
      of 31) in this particular population and a specificity of 92.2. The fall in CDT
      after 15 days withdrawal was 36%. CDT is thus a particularly useful marker for
      the diagnosis and follow-up of alcoholics with normal GGT levels.

PMID- 9622441
TI  - Voices of the afflicted.
AB  - Over the past 10 years, I have been privileged to conduct educational forums for
      audiences containing many recovering alcoholics or otherwise chemically dependent
      persons. In these forums about the addictive diseases and their treatment and
      research possibilities, significant interaction with the audience members occurs.
      During these interactions, certain anecdotal phenomena seem to predominate. The
      repetitive nature of these reports suggests the need for systematic
      investigation. As with editorial comments in major medical journals, observed
      phenomena and unanswered questions from those afflicted can be valuable in the
      generation of testable hypotheses. Perhaps the ideas presented herein will be
      useful in the development of future research on alcohol abuse and alcohol
      dependence.

PMID- 9622442
TI  - Ethanol feeding impairs innate immunity and alters the expression of Th1- and Th2
      phenotype cytokines in murine Klebsiella pneumonia.
AB  - The prolonged and excessive consumption of alcohol has been shown to predispose
      the host to a variety of infectious complications, which may be due, in part, to
      the inability to produce important activating cytokines. In this study, we
      assessed the effect of chronic alcohol ingestion on bacterial clearance,
      survival, and cytokine mRNA and protein expression in mice with Klebsiella
      pneumonia. Two-week ethanol feeding resulted in substantial impairment in the
      clearance of K. pneumoniae and decreased survival, compared with CD-1 mice
      receiving an isocaloric diet without ethanol. No differences were noted between
      control and ethanol groups in the total numbers or percent of bronchoalveolar
      lavage fluid neutrophils or macrophages at 24 and 48 hr post-intratracheal K.
      pneumoniae. Importantly, the lungs of alcohol-fed mice with Klebsiella pneumonia
      displayed a decrease or delay in the expression of interleukin (IL)-12 p35 and
      p40 mRNA and interferon-gamma mRNA, respectively, as well as reduced IL-12 and
      interferon-gamma protein levels, compared with controls. Conversely, a time
      dependent increase in lung IL-10 mRNAand protein was noted in ethanol-fed
      animals, compared with control animals challenged with K. pneumoniae. In summary,
      our studies indicate that ethanol ingestion results in a profound suppression of
      lung bacterial clearance and decreased survival in Klebsiella pneumonia, which
      occurs in association with a shift in the balance of lung cytokine mRNA and
      protein expression favoring Th2- rather than Th1-phenotype cytokines.

PMID- 9622443
TI  - Moderate, long-term, alcohol consumption potentiates normal, age-related spatial
      memory deficits in rats.
AB  - A modified "Samson" sucrose fading procedure was used to establish voluntary
      consumption of a 20% ethanol (EtOH) solution in male Sprague-Dawley rats for 18
      consecutive months. Intakes were stable over the life span, and corresponded to
      the moderate to high levels of intake typically observed in human "social"
      drinkers and alcoholics. The Morris Water Maze (WM), Olton Radial Arm Maze (RM),
      and a "balance beam" test were used to assess the effects of alcohol and aging on
      spatial memory and motor function. Aged EtOH-consuming rats (AGED/ALC)
      demonstrated impaired task acquisition, relative to aged controls (AGED), not
      reaching criterion performance in either spatial memory task even when given four
      additional days of training. AGED/ALC rats scored significantly lower on percent
      correct out of the first eight arm entries, and committed more perseverative
      errors in the RM. There were no significant performance differences between AGED
      and AGED/ALC rats on a balance beam test of fine motor coordination and
      equilibrium, suggesting that deficits observed in the RM and WM were not related
      to differential motor functioning. These results demonstrated that long-term,
      moderate, oral self-administration of EtOH, within the range typically consumed
      by humans, had adverse effects on spatial memory in rats, and that such a pattern
      of EtOH consumption seemed to exacerbate the decline in cognitive functioning
      associated with normal aging.

PMID- 9622444
TI  - Carbachol-stimulated Ca2+ increase in single neuroblastoma SH-SY5Y cells: effects
      of ethanol.
AB  - The effect of ethanol on the characteristics of carbachol-stimulated release of
      Ca2+ from intracellular Ca2+ stores was studied in single SH-SY5Y cells.
      Stimulation with carbachol, in the absence of extracellular Ca2+, elicited a
      rapid Ca2+ increase in SH-SY5Y cells peaking within seconds after addition of
      maximal agonist concentration. The Ca2+ response pattern in single cells
      resembled the population response, and there was no evidence of oscillatory
      changes in cytosolic [Ca2+] ([Ca2+]i). However, cell-to-cell variability could be
      detected in the magnitude and the latency time of the response, and in the rate
      of [Ca2+]i increase. In a carbachol dose-response analysis, the EC50 for the
      number of responsive cells and for the peak [Ca2+]i response was lower than that
      for carbachol-induced inositol 1,4,5-trisphosphate formation by a factor of 5 to
      50. Ethanol (100 mM) caused a significant suppression of the number of responsive
      cells, but only when cells were stimulated with nonsaturating carbachol
      concentrations (1 and 10 microM). The suppression by ethanol was evident
      primarily in those cells that gave a Ca2+ response after several seconds of
      stimulation, whereas cells that responded within the initial seconds of receptor
      stimulation remained relatively unaffected. In responding cells stimulated with
      10 microM carbachol, ethanol exposure also suppressed the maximal Ca2+ increase
      primarily in those cells that responded late. We suggest that ethanol suppression
      of muscarinic receptor-mediated signal transduction through the phospholipase C
      pathway may depend on the potentiation of feedback inhibition that requires
      receptor stimulation.

PMID- 9622445
TI  - Analysis of the 5-HT2 receptor ligands dimethoxy-4-indophenyl-2-aminopropane and
      ketanserin in ethanol discriminations.
AB  - Previous studies have suggested a modulatory role of the 5-HT2 receptor system in
      the behavioral effects of ethanol. The present study examined the discriminative
      stimulus effects of the 5-HT2A/2C agonist (-)-dimethoxy-4-indophenyl-2
      aminopropane (DOI) and the 5-HT2A antagonist ketanserin in rats trained to
      discriminate either 1.5 g/kg of ethanol from water (intragastrically, n = 7) or
      2.0 g/kg of ethanol from water (intragastrically, n = 8). In substitution tests,
      neither DOI (0.3 to 1.0 mg/kg, i.p.) nor ketanserin (3.0 to 17.0 mg/kg, i.p.)
      produced discriminative stimulus effects similar to either training dose of
      ethanol, although decreases in rates of responding were significant at the
      highest doses tested. Likewise, when given in combination with ethanol, neither 5
      HT2 ligand shifted the ethanol-dose response determination in either the 1.5 or
      2.0 g/kg ethanol training groups. DOI in combination with ethanol did not alter
      rates of responding, whereas ketanserin in combination with ethanol significantly
      decreased response rates. Thus, the 5-HT2A receptor ligands do not appreciably
      affect the discriminative stimulus effects of ethanol, in contrast to previous
      results with 5-HT1B ligands.

PMID- 9622446
TI  - Effect of pyrazole and dexamethasone administration on cytochrome P450 2E1 and 3A
      isoforms in rat liver and kidney: lack of specificity of p-nitrophenol as a
      substrate of P450 2E1.
AB  - The induction effects of pyrazole and dexamethasone (known to be specific to P450
      2E1 and 3A enzymes, respectively), given alone or simultaneously, were studied in
      rat liver and kidney microsomes. Pyrazole treatment induced the catalytic
      activity and the amount of P450 2E1 enzyme in both organs. Immunoreactive P450
      2E1 and 4-nitrophenol 2-hydroxylation increased 8- and 13-fold, respectively
      (versus control), in the kidney, but only 2.4- and 2.7-fold (versus control) in
      the liver after pyrazole treatment. As assessed by nifedipine oxidation activity,
      dexamethasone treatment increased the P450 3A catalytic activity approximately 4
      fold (versus control) in the liver, but not in the kidney, suggesting that P450
      3A was not inducible in the kidney. Pyrazole decreased P450 3A activity in the
      liver but did not modify it in the kidney. A combination of both chemicals
      induced both enzymes, but to a lesser extent than treatment with each single
      chemical compound. Furthermore, the 2-hydroxylation of p-nitrophenol, considered
      one of the most specific substrates for monitoring the level of P450 2E1, was
      mediated also by P450 3A, at least in dexamethasone-treated rats. Finally, this
      experimental work demonstrated that P450 3A induction is organ-specific, and it
      also demonstrated the lack of specificity of p-nitrophenol as a P450 2E1
      substrate.

PMID- 9622447
TI  - Alcohol decreases T-lymphocyte migration into lung tissue in response to
      Pneumocystis carinii and depletes T-lymphocyte numbers in the spleens of mice.
AB  - Previous work from our laboratory has shown that chronic alcohol consumption in
      mice creates immunosuppression sufficient to permit infection with the
      opportunistic pathogen Pneumocystis carinii. Host defense against P. carinii is
      critically dependent upon host T lymphocytes. In these experiments, we address
      the effect of chronic alcohol consumption on recruitment of T lymphocytes into
      infected lung tissue and on lymphocytes in host lymphoid tissue. We find that
      mice administered alcohol in drinking water and then inoculated with P. carinii
      show significantly decreased recruitment of CD4+ and CD8+ T lymphocytes into lung
      tissue in comparison with control mice. Additional experiments show significant
      depletion of CD4+ lymphocytes in spleens from alcohol mice and decreased numbers
      of activated T lymphocytes. Analysis of surface expression of the adhesion
      molecules LFA-1, VLA-4, and ICAM-1 show no significant differences in lymphocytes
      from alcohol-consuming mice, and lymphocyte chemotaxis in vitro is also
      unaltered. We conclude that chronic consumption of alcohol impairs lung
      recruitment of lymphocytes in response to an infectious challenge. This impaired
      lymphocyte recruitment may be a consequence of depletion of T lymphocytes in host
      lymphoid tissue. Impaired recruitment of lymphocytes may explain the increased
      morbidity and mortality of pulmonary infections in alcoholic subjects.

PMID- 9622448
TI  - More vasopressin mRNA in the paraventricular hypothalamic nucleus of alcohol
      preferring rats and high alcohol-drinking rats selectively bred for high alcohol
      preference.
AB  - Both the selectively bred alcohol-preferring (P) and high alcohol-drinking (HAD)
      rats exhibit alcohol preference, and develop tolerance to alcohol more quickly
      than their counterparts, the alcohol-nonpreferring (NP) and low alcohol-drinking
      (LAD) rats, respectively. It has been shown that the P rats retain developed
      tolerance longer than do NP rats, and alcohol drinking increases concurrently
      with the development of tolerance. Although alcohol preference and tolerance are
      fundamental elements of alcoholism, the exact mechanisms underlying these two
      phenotypes in P and HAD rats are not well understood. Recent studies have
      suggested that arginine vasopressin (AVP) may be involved in modulation of
      alcohol tolerance. Accordingly, this study was designed to examine whether the
      AVP mRNA level in the hypothalamus differs in rats that have been selectively
      bred for alcohol preference and nonpreference. A 35S-AVP antisense
      oligodeoxynucleotide probe was used for in situ hybridization to localize AVP
      mRNA in the paraventricular hypothalamic nucleus (PVN) and supraoptic nucleus
      (SON), two major sites for AVP synthesis in the hypothalamus. Quantitative
      autoradiography demonstrated that P rats had higher levels of AVP mRNA in the PVN
      than NP rats. Similarly, higher levels of AVP mRNA were also found in the PVN of
      HAD rats, compared with LAD rats. The AVP mRNA levels in the SON were similar in
      the alcohol-preferring and alcohol-nonpreferring rat lines. Basal plasma AVP
      levels were higher in NP rats than in P rats as determined by radioimmunoassay,
      whereas plasma AVP levels were not significantly different between HAD and LAD
      rats. The results suggest that increased AVP gene expression in the PVN may
      contribute to alcohol preference and the development of alcohol tolerance.

PMID- 9622449
TI  - Decreased sensitivity to the hypnotic effects of ethanol early in ontogeny.
AB  - Sensitivity to the hypnotic effects of ethanol was examined in Sprague-Dawley
      male and female rats at 16, 26, 36, 46, 56, or 96 days postnatally. Following
      administration of 3.5, 4.0, 4.5, or 5.0 g/kg of a 17% v/v ethanol solution, sleep
      times were recorded and blood alcohol levels (BALs) and brain alcohol levels
      (BrALs) were measured upon awakening. In addition to examining ethanol sleep time
      during ontogeny, data were used to estimate acute tolerance (indexed by the slope
      of the linear regressions of waking BALs and BrALs as a function of dose) and
      initial brain sensitivity to ethanol (indexed by calculating the y-intercept from
      the linear regression of BrALs as a function of sleep time). The results showed a
      marked increase in sensitivity to ethanol hypnosis during ontogeny, with young
      animals exhibiting shorter ethanol-induced sleep times and high waking BALs and
      BrALs. This ontogenetic increase in ethanol sensitivity was associated with a
      developmental decline in acute tolerance, with acute tolerance being most
      pronounced at postnatal day (P) 16 and evident only up to P36. Initial
      sensitivity conversely increased with age, with P16 pups showing lower initial
      brain sensitivity to ethanol than at all other ages. Gender differences emerged
      in adulthood, with males sleeping significantly longer than females at P56 and
      P96. These findings suggest that the marked insensitivity of young animals to the
      hypnotic effects of ethanol is related to both pronounced acute tolerance, as
      well as reduced initial brain sensitivity to ethanol early in life.

PMID- 9622450
TI  - Mouse strain differences in oral operant ethanol reinforcement under continuous
      access conditions.
AB  - The present experiment examined ethanol self-administration in C57BL/6J (C57) and
      DBA/2J (DBA) mice using a continuous access operant procedure. Adult male C57 and
      DBA mice were initially trained to perform a lever press response to obtain
      access to 10% w/v sucrose solution. Subsequently, the mice were placed in operant
      chambers on a continuous (23 hr/day) basis with access to food (FR1), 10% v/v
      ethanol (FR4), and water from a sipper tube. C57 mice displayed greater rates of
      responding on the ethanol-associated lever compared with DBA mice. Responding on
      the food lever was the same in both strains, but DBA mice consumed greater
      amounts of water. C57 mice consistently displayed both prandial and nonprandial
      episodes (bouts) of ethanol responding. DBA mice did not respond for ethanol in
      bouts. Following 50 consecutive sessions, ethanol concentration was altered every
      5 days. Response patterns were determined using 0, 5, 10, 20, and 30% v/v ethanol
      concentrations. C57 mice displayed concentration-dependent responding on the
      ethanol lever showing that ethanol was functioning as an effective reinforcer in
      this strain. In contrast, responding on the ethanol lever by DBA mice did not
      change as a function of ethanol concentration. Saccharin (0.2% w/v) was
      subsequently added to the ethanol mixture, and responding was examined at 0, 5,
      10, and 20% ethanol concentrations. Overall, ethanol lever responding was
      increased in both strains. As before, C57 mice showed higher levels of ethanol
      responding, compared with DBA mice. C57 mice also showed higher responding for
      saccharin alone. These results are consistent with findings that suggest orally
      administered ethanol is a more effective reinforcer in C57 mice than in DBA mice.
      Furthermore, C57 mice engage in ethanol-reinforced responding over a broader
      range of conditions than DBA mice.

PMID- 9622451
TI  - Prenatal ethanol exposure differentially alters behavior in males and females on
      the elevated plus maze.
AB  - Rodents prenatally exposed to ethanol demonstrate hypothalamic-pituitary-adrenal
      and behavioral hyperactivity to a variety of stressful situations. The present
      study examined both behavioral and corticosterone (CORT) responses to the
      elevated plus maze (+-maze), an anxiety- or fear-provoking task. Sprague-Dawley
      male and female offspring from fetal ethanol-exposed (E), pair-fed (PF), and ad
      libitum-fed control (C) groups were tested at 60 to 90 days of age. In experiment
      1, behavior was measured in animals exposed to the +-maze for 5 min on two
      consecutive days; 2 weeks later, both behavioral and CORT responses were measured
      in animals confined to the open and closed arms of the maze for 20 min. In
      experiment 2, animals were placed in an open field (OF) for 5 min before a single
      5-min exposure to the +-maze. Factor analysis of the scored behaviors from the
      two experiments indicated two main factors, designated "exploration" and "fear."
      E males and females both exhibited higher levels of exploratory behaviors when
      placed directly on the +-maze from their homecages without prior exposure to the
      OF, compared with C males and females. In addition, when confined to the closed
      arms of the +-maze, E males and females demonstrated higher levels of activity,
      compared with C males and females. After OF exposure, however, both E males and
      females demonstrated lower levels of exploratory behaviors than C males and
      females, and E females also had increased CORT levels, compared with PF and C
      females. Interestingly, E females, but not E males, showed an increase in fear
      related behaviors on the +-maze, compared with controls, regardless of prior OF
      exposure. These data demonstrate that prenatal ethanol exposure may
      differentially affect both behavioral and hormonal responses of males and females
      in an aversive behavioral task and suggest that there may be a sex difference in
      the sensitivity of the mechanism(s) underlying these responses.

PMID- 9622452
TI  - Fetal alcohol effects in rats exposed pre- and postnatally to a low dose of
      ethanol.
AB  - Wistar rats were exposed pre- and/or postnatally to a low dose of ethanol (1 g/kg
      of body weight of dams/day) via maternal peroral intubation. This dose
      significantly increased the mortality rate (23 to 32% vs. 7% in controls) in
      offspring exposed to ethanol during pregnancy, with a continued postnatal
      exposure having no additional effect. However, offspring cross-fostered to dams
      that had been exposed to ethanol only during gestation (the offspring themselves
      never being directly exposed to ethanol) displayed an even greater (59%)
      mortality. Growth of the offspring was initially delayed, but 9 weeks after birth
      their body weight reached that of the controls. The two-way active avoidance test
      showed an impairment, compared with the controls, of learning and memory in both
      male and female adolescent (9-week-old) rats, as well as in male (but not in
      female) 5-month-old rats born of dams exposed to ethanol during gestation and
      lactation. In the group of male rats treated prenatally and postnatally with
      ethanol, 60% were "poor learners," compared with 33% in the control group.
      Results suggest that ethanol at a dose of 1 g/kg/day administered to dams during
      gestation and lactation produced growth and behavioral changes in the offspring.

PMID- 9622453
TI  - Release and accumulation of neurotransmitters in the rat brain: acute effects of
      ethanol in vitro and effects of long-term voluntary ethanol intake.
AB  - Release from and accumulation in tissue slices of some neurotransmitters under
      acute ethanol in naive rats and in long-term voluntarily ethanol drinking rats
      were investigated. Slices of the rat caudatoputamen were prelabeled with
      [3H]choline and release of [3H]acetylcholine was stimulated through either N
      methyl-D-aspartate (NMDA) receptors or strychnine-sensitive glycine receptors.
      Ethanol in vitro at 2 per thousand, 4 per thousand, and 6 per thousand (34 mM, 68
      mM, and 102 mM, respectively) concentration-dependently depressed the maximum
      effect of the concentration-response curve of NMDA in naive rats. In contrast,
      voluntary ethanol consumption over months led to a significantly enhanced NMDA
      receptor response characterized by an increase in the maximum effect of the
      concentration-response curve. The glycine receptor-mediated release of
      [3H]acetylcholine, which is inhibited by acute ethanol in a competitive-like
      fashion, was not changed in animals that ingested ethanol over months.
      Electrically evoked release of [3H]noradrenaline ([3H]NA) and its presynaptic
      modulation by morphine through mu-opioid receptors in neocortical slices of the
      rat, preloaded with [3H]NA, was nearly identical in both ethanol-naive rats and
      in ethanol drinking rats. The accumulation of [3H]gamma-aminobutyric acid in rat
      cerebellum tissue was neither affected by acute ethanol in vitro nor after
      chronic ethanol consumption. In summary, long-term voluntary ethanol intake
      caused a significant increase in NMDA receptor function in the rat
      caudatoputamen, but did not result in changes in glycine-evoked [3H]acetylcholine
      release of electrically evoked [3H]NA release modulated by morphine or cerebellar
      [3H]gamma-aminobutyric acid accumulation.

PMID- 9622454
TI  - Ethanol induced changes in superoxide anion and nitric oxide in cultured
      microglia.
AB  - Induction of oxidative stress has been implicated as a causative factor in fetal
      alcohol syndrome although the source of reactive oxygen species is not clear. One
      potential source is the microglia, the CNS macrophage, which generate superoxide
      anion as part of their normal immune function. Our data indicate that chronic
      exposure to ethanol alters the function of cultured neonatal hamster microglia by
      inducing superoxide anion production in resting (nonstimulated) cells. An
      increase in superoxide anion was seen at 24 or 48 hr of ethanol treatment but was
      not seen during acute exposures of up to 3 hr. This effect was dose dependent and
      was maximal at 20 mM ethanol. Treatment with ethanol did not directly activate
      the respiratory burst seen in microglia and did not act as a priming agent to
      enhance phorbol-ester-stimulated superoxide anion production. Lipopolysaccharide
      mediated priming of microglial superoxide anion production was also not affected
      by exposure to 20 mM ethanol for 24 hr. Ethanol treatment, however, did depress
      nitric oxide (NO) levels in hamster microglia which had been stimulated to
      produce NO by polyinosinic:polycytidylic acid (poly I:C). Uptake of latex beads
      was increased by 24 hr of exposure to ethanol. The overall action of ethanol on
      neonatal hamster microglia is to shift the balance between the production of
      superoxide anion and NO. Because NO is protective to mammalian cells, these
      changes predict that oxidative stress in the CNS would be enhanced.

PMID- 9622455
TI  - Acute ethanol effects on focal cerebral ischemia in fasted rats.
AB  - The effects of acute ethanol intoxication were investigated in a rat model of
      unilateral middle cerebral artery occlusion. Groups of 5 to 8 male Sprague-Dawley
      rats were subjected to 4 hr of left middle cerebral artery occlusion. All groups
      were deprived of food overnight and were pretreated intraperitoneally with 5%
      dextrose solution (10 ml/kg), 20% ethyl alcohol in 5% dextrose solution (2 g/kg),
      or 30% ethyl alcohol in a 5% dextrose solution (3 g/kg) 1 hr before middle
      cerebral artery occlusion. Regional cerebral blood flow during ipsilateral
      occlusion was approximately 9.1 to 10% of baseline in all groups. The mean %
      brain water content in control, 2 g/kg ethanol-treated groups, and 3 g/kg ethanol
      treated groups were: in the ischemic core--81.6, 81.2, and 82.4; intermediate
      zone--80.5, 80.6, and 81.7; and outer zone--79.7, 79.7, and 80.8, respectively.
      Brain Na+ and K+ content in the three groups was related to water content, but
      much greater with ethanol pretreatment. The water content of the intermediate
      zones in the 3 g/kg ethanol-treated animals was significantly greater than in the
      control (p < 0.01 and 0.001) and the 2 g/kg ethanol-treated groups. One-way
      analysis of variance indicated a significant dose-effect relationship in which
      the lower dose of ethanol tended to reduce ischemic core water content, and the
      larger dose increased ischemic core water, compared with the control. None of the
      overnight fasted groups had any significant hyperglycemia. The group given 3 g/kg
      i.p. ethanol 1 hr before had exacerbated edema formation with a mean whole blood
      level of ethanol of approximately 230 mg/dl. The neurotoxic effects of high
      concentrations of ethanol were unrelated to any change in plasma glucose
      concentrations.

PMID- 9622456
TI  - Altered T-lymphocyte responsiveness to polyclonal cell activators is responsible
      for liver cell necrosis in alcohol-fed rats.
AB  - The role of T-cell activation in alcoholic liver disease was investigated in rats
      fed alcohol and subsequently exposed to concanavalin A (Con A). Following Con A
      injection (20 mg/kg body weight), greater increases in liver-to-body weight ratio
      and ALT levels were observed at 12 and 24 hr in rats fed ethanol, compared with
      control rats fed sucrose. Furthermore, increases in serum interleukin-6 and tumor
      necrosis factor-alpha levels were noted in ethanol-fed rats, with maximal levels
      detected at 4 hr declining thereafter, but remaining above control levels at 24
      hr. Analysis of T-cell subpopulations showed an increased percentage of CD4+,
      CD5+, and CD8+ T cells in blood from all groups, but not in liver perfusate. In
      contrast, a significant increase in the percentage of activated CD25+ T cells was
      detected in both blood and liver perfusate from rats fed ethanol even 24 hr after
      Con A injection. When CD4+ and CD8+ T cells from liver perfusate were cultured in
      the absence or presence of Con A, an increase in interleukin-6 and tumor necrosis
      factor-alpha production in supernatants was observed in ethanol-fed rats. In
      cultures stimulated with Con A, a 2- to 8-fold increase in cytokine production
      was detected, with intrahepatic CD4+ T cells being the major source.
      Immunohistological analysis revealed infiltration of CD4+ T cells around portal
      vein and central vein areas associated with fatty liver and severe hepatic
      necrosis. The results suggest that alcohol consumption induced a dysregulated T
      cell population that mediated hepatic necrosis following polyclonal activation
      with Con A.

PMID- 9622458
TI  - Fluoroquinolone-resistant Neisseria gonorrhoeae--San Diego, California, 1997.
AB  - The fluoroquinolones ciprofloxacin and ofloxacin are among the antimicrobials
      recommended for treating uncomplicated gonorrhea. Fluoroquinolone-resistant
      strains of Neisseria gonorrhoeae have been identified frequently during the 1990s
      in the Far East. In the United States, fluoroquinolone-resistant N. gonorrhoeae
      has been reported sporadically; resistance associated with clinical treatment
      failure has been reported previously in only one person, who probably acquired
      the infection in the Philippines. This report describes the results of an
      investigation in 1997 of two cases of gonococcal infection in the United States
      with strains with a higher level of fluoroquinolone resistance than reported
      previously; clinical treatment failure occurred in one case.

PMID- 9622457
TI  - Effect of ethanol administration on the level of dolichol in rat liver microsomes
      and Golgi apparatus.
AB  - Data obtained in our laboratory had suggested that acute ethanol administration
      (6 g/kg body weight) selectively and rapidly affects the intracellular system of
      protein glycosylation at the level of the Golgi apparatus. Dolichols are
      important membrane components, and dolichyl phosphate is a glycosyl sugar carrier
      for N-glycosylation of proteins in endoplasmic reticulum and is considered rate
      limiting for this process. In this study, modifications in the concentration and
      distribution of liver microsomal dolichols after acute ethanol administration
      were investigated. Between 3 and 24 hr after ethanol administration, the
      microsomal dolichyl phosphate concentration was significantly lower than in
      control animals. The highest reduction was observed at 12 hr (-52%). An earlier
      and more marked reduction of total dolichol was observed in the Golgi apparatus,
      and, in particular, in the secretory fraction F1 (-70% at 6 hr). Ethanol
      treatment of isolated hepatocytes led to a significant reduction of the de novo
      synthesis of both dolichyl phosphate and free dolichol. Moreover, in vitro
      experiments have demonstrated that pro-oxidant agents lead to a significant
      decrease of both free dolichol and dolichyl phosphate. Our results suggest that
      acute ethanol administration induces a marked decrease of dolichols, probably by
      increasing the degradation and impairing the biosynthetic pathway of these
      molecules.

PMID- 9622459
TI  - Diabetes during pregnancy--United States, 1993-1995.
AB  - Diabetes during pregnancy, whether pregestational (type 1 or type 2) or
      gestational, increases the risk for adverse maternal and infant outcomes (e.g.,
      congenital anomalies, cesarean delivery, macrosomia, and future metabolic
      abnormalities). Identification and careful management of diabetes during
      pregnancy can reduce poor maternal and infant outcomes. Diabetes prevalence and
      prenatal-care use varies among racial/ethnic groups and by maternal age and other
      characteristics. Higher than expected diabetes rates for women of childbearing
      age have been reported among many immigrant and other populations undergoing
      lifestyle changes (e.g., physical activity and diet). This report summarizes an
      analysis of U.S. birth certificates during 1993-1995 to describe maternal
      diabetes and associated prenatal care among racial/ethnic groups and updates a
      previous report.

PMID- 9622460
TI  - Progress toward global eradication of poliomyelitis, 1997.
AB  - In 1988, the World Health Assembly adopted the goal of eradicating poliomyelitis
      by 2000. Substantial progress toward this goal has been reported from many areas
      of the world. Since 1988, all but four countries with endemic polio have
      conducted National Immunization Days (NIDs), and most countries have established
      sensitive surveillance systems for acute flaccid paralysis (AFP). This report
      updates progress toward global polio eradication in 1997 based on data available
      from the World Health Organization (WHO) as of May 18, 1998.

PMID- 9622461
TI  - Reconstitution of basement membrane after 'sandwich-technique' skin grafting for
      severe burns demonstrated by immunohistochemistry.
AB  - Reconstitution of basement membrane structures after "sandwich-technique"
      grafting of severe deep burns is demonstrated with use of immunohistochemical
      techniques. Cryosections of human skin after epifascial burn wound excision and
      sandwich grafting were stained with monoclonal antibodies against type IV and VII
      collagen, polyvalent antiserum against type VI collagen, and polyvalent antibody
      against laminin. Standard hematoxylin and eosin histologies were performed for
      morphologic correlation. Reorganization of the mesenchymal border zone (basement
      membrane), after transplantation of extremely expanded split-thickness skin
      autografts overlaid with glycerolized split-thickness skin allografts onto
      debrided human full-thickness wounds, occurred from day 5 to day 35. The
      autografts reepithelize the spaces between the mesh structure, which has been
      covered primarily exclusively with allogenic skin, and form a layered squamous
      epithelium, with an underlying three-dimensional basket-weave array of collagen
      in the remodeled neodermis after epifascial excision. Immunochemical techniques
      detect the reconstitution of a basement membrane zone with a typical architecture
      and distribution of laminin, type IV, and type VII collagen being built up 1 week
      to 5 weeks after sandwich grafting. These structures can be seen in the
      autografts during the first 2 weeks and are consistent in the whole reconstituted
      skin after day 35. To our knowledge this is the first report of the expression of
      type VI collagen in these types of wounds. The findings are compared with the
      expression of type VI collagen in healthy skin. The results indicate that the
      modified sandwich-grafting technique is an adequate means for early burn wound
      closure and resurfacing of third-degree burn wounds and leads to the
      reconstitution of dermal qualities.

PMID- 9622462
TI  - A finite-element model predicts thermal damage in cutaneous contact burns.
AB  - Thermal injury results from exposure of skin elements to an externally applied
      heat source. Finite-element analysis of heat transfer in cutaneous burns allows
      for an accurate prediction of tissue time-temperature relationships throughout
      the exposed tissue. A two-dimensional, axisymmetric, finite-element model of a
      contact burn was constructed, and damage integrals were calculated by applying
      the Arrhenius equation to the time-temperature profiles at each point. The
      epidermis, dermis, and subcutaneous fat were modeled as uniform elements with
      distinct thermal properties. Heated aluminum blocks were applied to Yorkshire
      pigs for 10 to 80 seconds to produce contact burns. Wound biopsies taken at 1,
      24, and 48 hours were examined histologically and measured for the depth of burn.
      A significant deepening of the gelatinized tissue was observed in tissue taken
      from 1 hour to 24 hours. The finite-element prediction of cutaneous contact burn
      damage correlated well with histologic observations in this porcine model.

PMID- 9622463
TI  - Reduction in mortality in pediatric patients with inhalation injury with
      aerosolized heparin/N-acetylcystine [correction of acetylcystine] therapy.
AB  - Smoke-inhalation injury causes a destruction of the ciliated epithelium that
      lines the tracheobronchial tree. Casts produced from these cells,
      polymorphonuclear leukocytes and mucus, can cause upper-airway obstruction,
      contributing to pulmonary failure. We have reported that a combination of
      aerosolized heparin and a mucolytic agent, N-acetylcystine [corrected], can
      ameliorate cast formation and reduce pulmonary failure secondary to smoke
      inhalation. In this study, 90 consecutive pediatric patients between 1985 and
      1995 who had bronchoscopically diagnosed inhalation injury requiring ventilatory
      support were studied. Forty-three children admitted between 1985 and 1989 acted
      as controls. Forty-seven children admitted between 1990 and 1994 received 5000
      units of heparin and 3 ml of a 20% solution of N-acetylcystine [corrected]
      aerosolized every 4 hours the first 7 days after the injury. All patients were
      extubated when they were able to maintain spontaneously a PaO2/FIO2 ratio of more
      than 400. The number of patients requiring reintubation for successive pulmonary
      failure was recorded, as was mortality. The results indicate a significant
      decrease in reintubation rates, in incidence of atelectasis, and in mortality for
      patients treated with the regimen of heparin and N-acetylcystine [corrected] when
      compared with controls. Heparin/N-acetylcystine [corrected] nebulization in
      children with massive burn injury and smoke-inhalation injury results in a
      significant decrease in incidence of reintubation for progressive pulmonary
      failure and a reduction in mortality.

PMID- 9622464
TI  - Effect of 'Compound R' on thermal burn and full-depth wound contracture in fuzzy
      rats.
AB  - We evaluated the efficacy of Compound R emulsion on wound contraction in fuzzy
      rats. While the rats were under anesthesia, two mirror-image burn wounds were
      inflicted on the depilated back skin of each. Wounds were assigned randomly to
      treatment or placebo (oil), and the wound-scar areas were measured when they
      healed. A second set of wounds was created by taking two 6 millimeter punch
      biopsies from each rat and treated with Compound R or placebo. Under anesthesia,
      areas of the wound were measured on days 0, 5, 8 and on healing. Mean+/-SE areas
      for the healed burn wounds were: 151+/-24 mm2 for the treated and 102+/-26 mm2
      for the placebo side (paired Student's t test, t=4.21, p=0.0015). Areas for
      Compound R-treated punch biopsy-induced wounds were significantly larger than
      placebo treated at each time point (p < 0.01). Results from this study show that
      Compound R impeded wound contraction.

PMID- 9622465
TI  - A retrospective study of the incidence and prevalence of thermal corneal injury
      in patients with burns.
AB  - The clinical course of thermal corneal injuries is not well described. A review
      of 1750 burn admissions to a regional burn center between 1979 through 1993 was
      done to determine the clinical course of thermal corneal injuries. Twenty-five
      out of 1750 burn admissions (1%) presented with a thermal corneal injury. Corneal
      injuries were identified with use of a fluorescein dye and a Wood's lamp.
      Ophthalmologic consultation was obtained for those identified. Data were analyzed
      with the Fisher's exact test and the unpaired two-tailed Student's t test.
      Patients with thermal corneal injury did not differ demographically from other
      patients with burn injury. Open-flame burns were the most common cause of injury.
      Improvement of corneal injury occurred in all survivors who had an intact globe
      on initial examination. Initial visual acuity was not a good predictor of
      outcome, and long-term complications were uncommon.

PMID- 9622466
TI  - Treatment-resistant pain and distress during pediatric burn-dressing changes.
AB  - Recent research has suggested some efficacy for the use of hypnosis in the
      control of pain and distress in a pediatric population undergoing painful medical
      procedures. Here, we study a sample (N=23) of pediatric subjects undergoing burn
      dressing changes and receiving either an imagery-based or control (social
      support) treatment. Subjects' levels of distress were assessed with the
      Observational Scale of Behavioral Distress. Results indicated that distress
      behaviors in this population can be measured reliably using this scale. However,
      no support was found for the main hypothesis that imagery treatment would be
      superior to control treatment in the alleviation of distress, nor were these
      treatments effective in comparison to baseline conditions. We discuss the
      formidable problem that burn and dressing-change pain presents, as well as the
      reasons why this treatment attempt might have failed to have the predicted
      effects. We also discuss important developmental considerations regarding the
      adequate assessment of pain and distress.

PMID- 9622467
TI  - Opiate-induced respiratory depression in young pediatric burn patients.
AB  - Three children younger than 5 with minor burns (< 5% total body surface area)
      experienced opiate-induced respiratory depression early in hospitalization. This
      prompted a decrease in the recommended opiate analgesic-dose ranges on our
      pediatric worksheet. In reviewing 57 admissions, 31 pre- and 26 post-dose change,
      the amount of opioid equivalents/kg received on admission day did not differ
      significantly. However, the incidence of respiratory depressive events decreased.
      Lower opiate-dose guidelines might improve the safe administration of these
      medications to young children. Other factors- such as concomitant sedative
      medications, previously administered opiate analgesics, and underlying medical
      conditions-also must be considered when giving initial doses of opiate analgesics
      in the burn center.

PMID- 9622468
TI  - Posttraumatic stress disorder in burn populations: a critical review of the
      literature.
AB  - This review of the literature examines studies concerning posttraumatic stress
      disorder (PTSD) in burn populations. Retrospective, cross-sectional, and
      prospective research and case studies are critiqued. Although the data are
      equivocal, several trends are clearly emerging. Though severity of burn and
      degree of disfigurement did not consistently predict PTSD, subjective variables
      were better predictors. There was a clear trend for patients who had no symptoms
      of PTSD while hospitalized to have PTSD develop after discharge. Finally,
      prevalence rates of PTSD vary greatly based on time of screening. Methodological
      problems with studies were related to sampling and follow-up; suggestions for
      future research are provided.

PMID- 9622469
TI  - Burn injuries benefit from massage therapy.
AB  - Twenty-eight adult patients with burns were randomly assigned before debridement
      to either a massage therapy group or a standard treatment control group. State
      anxiety and cortisol levels decreased, and behavior ratings of state, activity,
      vocalizations, and anxiety improved after the massage therapy sessions on the
      first and last days of treatment. Longer-term effects were also significantly
      better for the massage therapy group including decreases in depression and anger,
      and decreased pain on the McGill Pain Questionnaire, Present Pain Intensity
      scale, and Visual Analogue Scale. Although the underlying mechanisms are not
      known, these data suggest that debridement sessions were less painful after the
      massage therapy sessions due to a reduction in anxiety, and that the clinical
      course was probably enhanced as the result of a reduction in pain, anger, and
      depression.

PMID- 9622470
TI  - Sterilizing a clinitron air-fluidized bed with colistine powder.
AB  - After cross-patient infection occurred with the Clinitron bed, we looked for a
      way to deliver an antibiotic agent into the inner environment of the Clinitron
      bed through the filtering system in a manner that would sterilize the
      contaminated microspheres. Multiple cultures of the contaminated microspheres
      from the Clinitron air-fluidized bed were done, and the infecting microorganisms
      were identified. The appropriate antibiotic powder was delivered through the
      filter system of the bed, and the microspheres were recultured after treatment.
      After an antibiotic powder was administered, the microspheres cultured were
      sterile. We found that the Clinitron bed can be safely, easily, and inexpensively
      sterilized and reused by the administration of antibiotic agent through the air
      filter system. Furthermore resistant bacteria can be treated with antibiotic
      agent sparingly used in a clinical setting because of toxicity.

PMID- 9622471
TI  - Work status and attrition from longitudinal studies are influenced by psychiatric
      disorder.
AB  - Participants (n=95) were assessed at the time of discharge and at 4 and 12 months
      after discharge in regard to work status and psychiatric history both before and
      after the burn injury. Complex psychiatric comorbidity and substance abuse
      disorders that occurred before the burn injury each significantly raised the risk
      of unemployment before the burn injury; preburn substance abuse also affected
      unemployment at 4 months after the burn injury. Trends for higher unemployment
      rates at 12 months after discharge also were noted among those with a preburn
      history of complex psychiatric comorbidity and alcohol use, anxiety, or mood
      disorder. Preburn substance-use disorder raised the risk of attrition from the 12
      month study; whereas, those diagnosed at the time of discharge with post
      traumatic stress disorder or with two or more current psychiatric disorders after
      the burn injury dropped out less often. The greater risk for unemployment and
      attrition observed among subjects with psychiatric disorders before the burn
      injury suggests the need for routine screening, tracking, and assistance in
      accessing supportive or rehabilitative services to remove barriers to employment.

PMID- 9622472
TI  - Casting guidelines, tips, and techniques: proceedings from the 1997 American Burn
      Association PT/OT Casting Workshop.
AB  - Approximately 100 therapists attended the PT/OT Casting Workshop at the twenty
      ninth Annual Meeting of the American Burn Association in New York City, N.Y., on
      March 20, 1997. The workshop consisted of four groups: two demonstrating
      hand/wrist casting and two demonstrating casting of the foot/ankle. Participants
      had the opportunity to attend one upper extremity group and one lower extremity
      group lasting approximately 50 minutes each. Instructors provided a demonstration
      of a casting procedure while addressing general guidelines, indications,
      contraindications, and precautions related to casting each area. Thorough
      handouts were provided, and each participant had the opportunity to apply two
      casts. The following article is a compilation of the four handouts and their
      bibliographies.

PMID- 9622473
TI  - Descriptive statistics: practical applications of the NATIONAL TRACS/ABA Burn
      Registry.

PMID- 9622474
TI  - State study of pyrotechnics-related injuries and property damage.
AB  - In December 1993, the State of North Carolina legalized the sale of certain types
      of fireworks. To date, no study has examined the impact of legalization of
      fireworks on health care and public safety. The purpose of this study was to
      examine the impact of legalized pyrotechnics specific to our state with regard to
      injury, property damage, and suppression costs. The population groups surveyed
      were the state fire departments, county fire marshals, hospital emergency
      departments, and county forest rangers. Each group was asked to complete a
      questionnaire on all incidents involving pyrotechnics devices, both legal and
      illegal, used during the study period. A total of 233 responses were received
      from the 1644 agencies surveyed. Forty-one injuries and 129 fireworks-related
      fires were reported. Total property loss was $185,570. Property loss, injury
      costs, and fire suppression costs totaled $799,450. This study provides a very
      conservative estimate of the problem within our state. Stronger legislation to
      restrict access to pyrotechnics may reduce the damage and costs they cause.

PMID- 9622475
TI  - On an island by myself: women of color with facial distinctions.
AB  - Twenty-five women of color with early or late-onset facial distinctions between
      the ages of 18 and 44 were interviewed as part of a larger study investigating
      the psychosocial sequelae of facial distinction. Women were asked to report their
      thoughts about the ways other people perceived them, about their self
      perceptions, and about difficult aspects of having a facial distinction. Findings
      indicate that facial distinction is a salient, pervasive, and overwhelming
      physical attribute. Society exerts a negative influence on all people with
      distinctions. This is accomplished by strictly defining what is an acceptable
      physical appearance and what is not and excluding those who do not conform to the
      standard. The findings point towards new areas for research including cross
      cultural, cross-gender, and cross-distinction studies. Recommendations for
      clinical intervention are offered.

PMID- 9622476
TI  - 3-Nitrotyrosine in the proteins of human plasma determined by an ELISA method 

PMID- 9622477
TI  - Reverse transcriptase of mouse mammary tumour virus: expression in bacteria,
      purification and biochemical characterization 

PMID- 9622478
TI  - Construction of a family of Cys2His2 zinc binding sites in the hydrophobic core
      of thioredoxin by structure-based design.
AB  - A semi-automated, rational design strategy has been used to introduce a family of
      seven single, mononuclear Cys2His2 zinc sites at various locations in the
      hydrophobic core of Escherichia colithioredoxin, a protein that is normally
      devoid of metal centers. The electronic absorption spectra of the CoII complexes
      show that five of these designed proteins bind metal with the intended
      tetrahedral geometry. The designed sites differ in their metal-binding constants
      and effects on protein stability. Since these designs are constructed within the
      same host protein framework, comparison of their behavior allows a qualitative
      evaluation of dominant factors that contribute to metal-binding and metal
      mediated protein stabilization. Metal-binding constants are dominated by steric
      interactions between the buried, designed coordination sphere and the surrounding
      protein matrix. Metal-mediated stability is the consequence of differential
      binding to the native and unfolded states. Increased interactions with the
      unfolded state decrease the stabilizing effect of metal binding. The affinity for
      the unfolded state is dependent on the placement of the primary coordination
      sphere residues within the linear protein sequence. These results indicate that a
      protein fold can have a remarkably broad potential for accommodating metal
      mediated cross-links and suggest strategies for engineering protein stability by
      constructing metal sites that maximize metal binding to the native state and
      minimize binding to the unfolded state.

PMID- 9622479
TI  - A new metal-binding site in photosynthetic bacterial reaction centers that
      modulates QA to QB electron transfer.
AB  - Isolated reaction centers (RCs) from Rhodobacter sphaeroides were found to bind
      Zn(II) stoichiometrically and reversibly in addition to the 1 equiv of non-heme
      Fe(II). Metal and EPR analyses confirm that Zn(II) is ligated to a binding site
      that is distinct from the Fe site. When Zn(II) is bound to this site, electron
      transfer between the quinones QA and QB (QA-QB --> QAQB-) is slowed and the room
      temperature kinetics become distributed across the microsecond to millisecond
      time domain. This effect of metal binding on the kinetics is similar to the more
      global effect of cooling RCs to 2 degreesC in the absence of Zn(II). This
      suggests that Zn(II) binding alters localized protein motions that are necessary
      for rapid QA-QB --> QAQB- electron transfer. Inspection of the RC crystal
      structure suggests a cluster of histidine ligands located beneath the QB binding
      pocket as a potential binding site.

PMID- 9622480
TI  - Functional analysis of amino acid residues essential for activity in the Na+/H+
      exchanger of fission yeast.
AB  - We identified amino acid residues important for activity of sod2, the Na+/H+
      antiporter of Schizosaccharomyces pombe. We mutated all eight His residues of
      sod2 into Arg. Only His367-->Arg affected function and resulted in complete
      inability of sod2 to allow growth of S. pombe in LiCl-containing medium. Mutant
      S. pombe (H367R) could not expel sodium in acidic (pH 4.0) medium and were
      defective in their ability to alkalinize external medium. When His367 was
      replaced by Asp, sodium export of S. pombe was suppressed at acidic pH while the
      sodium-dependent proton influx at pH 6.1 was increased compared to wild type. We
      also mutated three residues conserved in putative membrane regions of various
      eukaryotic and prokaryotic Na+/H+ exchangers. S. pombe containing Asp241-->Asn
      and Asp266, 267-->Asn mutations had greatly impaired growth in LiCl-containing
      medium. In addition, sodium-dependent proton influx at external pH 6. 1 was
      impaired. Sodium export from S. pombe cells at external pH 4.0 was also almost
      completely abolished by the D266,267N mutation; however, the D241N mutant protein
      retained almost normal Na+ export. The results demonstrate that His367, Asp241,
      and Asp266,267 are important in the function of the eukaryotic Na+/H+ exchanger
      sod2.

PMID- 9622481
TI  - The origin of differences in the physical properties of the equilibrium forms of
      cytochrome b5 revealed through high-resolution NMR structures and backbone
      dynamic analyses.
AB  - On the basis of a comparison of high-resolution solution structures calculated
      for both equilibrium forms of rat ferrocytochrome b5, differences in reduction
      potential and thermodyanmic stability have been characterized in terms of
      significant structural and dynamic differences between the two forms. The
      dominant difference between A and B conformations has long been known to be due
      to a 180 degrees rotation of the heme in the binding pocket about an axis defined
      by the alpha- and gamma-meso carbons, however, the B form has not been
      structurally characterized until now. The most significant differences observed
      between the two forms were the presence of a hydrogen bond between the 7
      propionate and the S64 amide in the A form but not the B form and surprisingly a
      displacement of the heme out of the binding pocket by 0.9 A in the B form
      relative to the A form. The magnitude of other factors which could contribute to
      the known difference in reduction potentials in the bovine protein [Walker, F.
      A., Emrick, D., Rivera, J. E., Hanquet, B. J., and Buttlaire, D. H. (1988) J. Am.
      Chem. Soc. 110, 6234-6240], such as differences in the orientation of the axial
      imidazoles and differences in hydrogen bond strength to the imidazoles, have been
      evaluated. The dominant effector of the reduction potential would appear to be
      the lack of the hydrogen bond to the S64 amide in the B form which frees up the
      propionate to charge stabilize the iron in the oxidized state and thus lower the
      reduction potential of the B form. The structure we report for the A form, based
      on heteronuclear NMR restraints, involving a total of 1288 restraints strongly
      resembles both the X-ray crystal structure of the bovine protein and a recently
      reported structure for the A form of the rat protein based on homonuclear data
      alone [Banci, L., Bertini, I., Ferroni, F., and Rosato, A. (1997) Eur. J.
      Biochem. 249, 270-279]. The rmsd for the backbone atoms of the A form is 0.54 A
      (0.92 A for all non-hydrogens). The rmsd for the backbone of the B form is 0.51 A
      (0. 90 A for all non-hydrogen atoms). An analysis of backbone dynamics based on a
      model-free analysis of 15N relaxation data, which incorporated axially symmetric
      diffusion tensor modeling of the cytochrome, indicates that the protein is more
      rigid in the reduced state relative to the oxidized state, based on a comparison
      with order parameters reported for the bovine protein in the oxidized state
      [Kelly, G. P., Muskett, F. W., and Whitford, D. (1997) Eur. J. Biochem. 245, 349
      354].

PMID- 9622482
TI  - Solution structure of murine macrophage inflammatory protein-2.
AB  - The solution structure of murine macrophage inflammatory protein-2 (MIP-2), a
      heparin-binding chemokine that is secreted in response to inflammatory stimuli,
      has been determined using two-dimensional homonuclear and heteronuclear NMR
      spectroscopy. Structure calculations were carried out by means of torsion-angle
      molecular dynamics using the program X-PLOR. The structure is based on a total of
      2390 experimental restraints, comprising 2246 NOE-derived distance restraints, 44
      distance restraints for 22 hydrogen bonds, and 100 torsion angle restraints. The
      structure is well-defined, with the backbone (N, Calpha, C) and heavy atom atomic
      rms distribution about the mean coordinates for residues 9-69 of the dimer being
      0.57 +/- 0.16 A and 0.96 +/- 0.12 A, respectively. The N- and C-terminal residues
      (1-8 and 70-73, respectively) are disordered. The overall structure of the MIP-2
      dimer is similar to that reported previously for the NMR structures of MGSA and
      IL-8 and consists of a six-stranded antiparallel beta-sheet (residue 25-29, 39
      44, and 48-52) packed against two C-terminal antiparallel alpha-helices. A best
      fit superposition of the NMR structure of MIP-2 on the structures of MGSA, NAP-2,
      and the NMR and X-ray structures of IL-8 are 1.11, 1.02, 1.27, and 1.19 A,
      respectively, for the monomers, and 1.28, 1.10, 1.55, and 1.36 A, respectively,
      for the dimers (IL-8 residues 7-14 and 16-67, NAP-2 residues 25-84). At the
      tertiary level, the main differences between the MIP-2 solution structure and the
      IL-8, MGSA, and NAP-2 structures involve the N-terminal loop between residues 9
      23 and the loops formed by residues 30-38 and residues 53-58. At the quaternary
      level, the difference between MIP-2 and IL-8, MGSA, or NAP-2 results from
      differing interhelical angles and separations.

PMID- 9622483
TI  - Complexes of adenosine deaminase with two potent inhibitors: X-ray structures in
      four independent molecules at pH of maximum activity.
AB  - Adenosine deaminase, which catalyzes the irreversible hydrolytic deamination of
      adenosine nucleosides to inosine nucleosides and ammonia, is a key enzyme in
      purine metabolism and lymphoid development. The X-ray structures of murine
      adenosine deaminase with bound potent inhibitors (Ki values approximately 10(-13)
      M) (8R)-hydroxyl-2'-deoxycoformycin (pentostatin), a transition state analogue,
      and (6S)-hydroxyl-1,6-dihydropurine riboside, a reaction coordinate analogue,
      have been determined and refined to resolutions of 2.6 and 1.95 A, respectively.
      Crystals of both complexes were obtained at pH 7, where the enzyme is fully
      active, in an identical space group with the asymmetric unit containing four
      molecules. In addition to the very high degree of similarity between the four
      independent molecules in each complex structure, there is also considerable
      structural similarity of the complex with the dihydropurine riboside with that of
      an identical complex previously determined at pH 4.2 where the enzyme is 20%
      active. The interactions between the enzyme and the two analogues are extremely
      similar. These include the coordination of the 8R- or 6S-hydroxyl group of the
      analogues to the Zn2+ which mainly contributes to the strong potency and very
      high degree of stereospecificity of inhibition by these analogues. The
      interactions are further indicative of the structural and chemical requirements
      of substrates. These structures and recent site-directed mutagenesis have further
      shed light on the catalytic mechanism of the enzyme.

PMID- 9622484
TI  - Crystal structure and enzyme mechanism of Delta 5-3-ketosteroid isomerase from
      Pseudomonas testosteroni.
AB  - Bacterial Delta 5-3-ketosteroid isomerase (KSI) from Pseudomonas testosteroni has
      been intensively studied as a prototype for understanding an enzyme-catalyzed
      allylic rearrangement involving intramolecular proton transfer. Asp38 serves as a
      general base to abstract the proton from the steroid C4-H, which is a much
      stronger base than the carboxyl group of this residue. This unfavorable proton
      transfer requires 11 kcal/mol of energy which has to be provided by favorable
      interactions between catalytic residues and substrate in the course of the
      catalytic reaction. How this energy is provided at the active site of KSI has
      been a controversial issue, and inevitably the enzyme mechanism is not settled.
      To resolve these issues, we have determined the crystal structure of this enzyme
      at 2.3 A resolution. The crystal structure revealed that the active site
      environment of P. testosteroni KSI is nearly identical to that of Pseudomonas
      putida KSI, whose structure in complex with a reaction intermediate analogue we
      have determined recently. Comparison of the two structures clearly indicates that
      the two KSIs should share the same enzyme mechanism involving the stabilization
      of the dienolate intermediate by the two direct hydrogen bonds to the dienolate
      oxyanion, one from Tyr14 OH and the other from Asp99 COOH. Mutational analysis of
      the two residues and other biochemical data strongly suggest that the hydrogen
      bond of Tyr14 provides the more significant contribution than that of Asp99 to
      the requisite 11 kcal/mol of energy for the catalytic power of KSI.

PMID- 9622486
TI  - The B-DNA dodecamer at high resolution reveals a spine of water on sodium.
AB  - We describe a very accurate addition (called structure X here) to the B-DNA
      dodecamer family of X-ray structures. Our results confirm the observation of Drew
      and Dickerson [(1981) J. Mol. Biol. 151, 535-556] that the spine of hydration in
      AT tract DNA is two layers deep. However, our results suggest that the primary
      spine is partially occupied by sodium ions. We suggest that many sequence
      dependent features of DNA conformation are mediated by site specific binding of
      cations. For example, preferential localization of cations, as described here
      within the minor groove of structure X, is probably the structural origin of AT
      tract bending and groove narrowing. The secondary spine, which does not interact
      directly with the DNA, is as geometrically regular as the primary spine,
      providing a model for transmission of sequence information into solvent regions.
      A fully hydrated magnesium ion located in the major groove of structure X appears
      to pull cytosine bases partially out from the helical stack, exposing pi-systems
      to partial positive charges of the magnesium ion and its outer sphere. A
      partially ordered spermine molecule is located within the major groove of
      structure X. Dodecamer structures are derived from crystals of [d(CGCGAATTCGCG)]2
      in space group P212121 (a = 25 A, b = 40 A, and c = 66 A). On average, those
      crystals diffracted to around 2.5 A resolution with 2500 unique reflections.
      Structure X, with the same space group, DNA sequence, and crystal form as the
      "Dickerson dodecamer", is refined against a complete, low-temperature, 1.4 A
      resolution data set, with over 11000 reflections. Structure X appears to be
      conformationally more ordered than previous structures, suggesting that at least
      a portion of the conformational heterogeneity previously attributed to DNA
      sequence in fact arises from experimental error.

PMID- 9622485
TI  - Tyrosine 64 of cytochrome c553 is required for electron exchange with formate
      dehydrogenase in Desulfovibrio vulgaris Hildenborough.
AB  - Replacement of tyrosine 64 by alanine in cytochrome c553 from Desulfovibrio
      vulgarisHildenborough prevents electron transfer with the formate dehydrogenase.
      Biophysical and biochemical studies show that the protein is correctly folded and
      that the oxidoreduction potential is not modified. The solution structure of the
      mutant cytochrome determined by two-dimensional (2D) NMR clearly establishes that
      the overall fold of the molecule is nearly identical to that of the wild-type
      cytochrome. The electrostatic surface charge distributions for the wild-type and
      mutant cytochrome are similar, suggesting that the interaction site of the
      physiological partners is not modified by the mutation. The lack of the aromatic
      ring induces slight destabilization of the hydrophobic core of the molecule and
      modifications of the hydrogen bond at position 64, as well as conformational
      disorder of the side chain of K63. The loss of the hydrogen bond from tyrosine 64
      and the increase of the solvent exposure of the heme are probably responsible of
      the loss of electron transfer between formate dehydrogenase and cytochrome c553.

PMID- 9622487
TI  - Role of the colchicine ring A and its methoxy groups in the binding to tubulin
      and microtubule inhibition.
AB  - The roles of the methoxy substituents on ring A of two ring colchicine (COL)
      analogues were probed by the synthesis of a number of drugs and the examination
      of their effect on binding to tubulin, inhibition of microtubule assembly, and
      induction of GTPase activity. Selective elimination of ring A methoxy groups at
      positions 2, 3, and 4 weakened all three processes. The effects on binding and
      inhibition were independent of the nature of ring C (or C'). Specifically,
      excision of the 2- or 3-methoxy groups weakened binding by ca. 0.4 kcal mol-1,
      while that of the 4-methoxy group of ring A was weakened by 1.36 +/- 0.15 kcal
      mol-1. The effect on the inhibition of microtubule assembly, expressed as the
      equilibrium constant for the binding of the tubulin-drug complex to the end of a
      microtubule, was more complex and strongly dependent on the nature of ring C (or
      C'). This was attributed to the abilities of various groups on ring C' to
      overcome the wobbling in the tubulin-drug complex introduced by the weakening of
      the anchoring provided by ring A. It is concluded that ring A of COL is not
      germane to the mechanism of the inhibition of tubulin self-assembly. It serves
      only as a complex-stabilizing anchor. The control of this process resides in the
      interactions that key oxygen atoms of ring C of COL or C' of structural analogues
      establish with the protein. It is proposed that the 4-methoxy group of ring A
      serves as a key attachment point for immobilization of the drugs on the protein.

PMID- 9622488
TI  - How colipase-fatty acid interactions mediate adsorption of pancreatic lipase to
      interfaces.
AB  - Colipase is a cofactor protein which forms a 1:1 complex with pancreatic lipase.
      This facilitates lipase adsorption to phosphatidylcholine-rich interfaces,
      presumably as a consequence of the higher affinity of colipase for such
      interfaces. According to this model, the presence of colipase in an interface
      should be sufficient to enable lipase adsorption from the aqueous phase. To test
      this hypothesis, mixed monolayers of colipase, phosphatidylcholine, and fatty
      acid at the argon-buffer interface were exposed to lipase injected into the
      stirred aqueous subphase. Spread colipase remained associated with the lipid
      monolayer in a surface pressure- and lipid composition-dependent manner. For
      example, with diacylphosphatidylcholine alone, colipase remained in the lipid
      monolayer at surface pressures </=20 mN/m, but with pure fatty acid this was
      increased to approximately 40 mN/m. Contrary to the existing paradigm, the
      presence of colipase in a lipid monolayer was not sufficient to enable the
      adsorption of lipase to the interface. Fatty acid was also required, and its
      ability to enhance lipase adsorption over that observed in the absence of
      colipase was dependent on the fatty acid and colipase mole fractions. These
      results support the hypothesis that colipase concentrates fatty acids laterally
      at its periphery and suggest that, together with lipase-colipase interaction, the
      fatty acid-rich nano-domain surrounding colipase facilitates lipase adsorption in
      the 'flap-opened' conformation.

PMID- 9622489
TI  - Flexibility involving the intermolecular dityrosyl cross-links of enzymatically
      polymerized calmodulin.
AB  - The role of dityrosine as a fluorescent crossbridge between adjacent calmodulin
      molecules within the high molecular mass polymers that are generated by
      Arthromyces peroxidase-catalyzed cross-linking [Malencik, D. A., and Anderson, S.
      R. (1996) Biochemistry 35, 4375] has been examined in frequency domain
      fluorescence anisotropy studies. Measurements on a polymer fraction possessing a
      range of molecular masses > 96 000 in NaDodSO4 polyacrylamide gel electrophoresis
      demonstrate predominating fast local rotations involving the dityrosyl moieties.
      Normal distribution analyses of the results show peak rotational correlation
      times of 0.6 ns (zero Ca2+) and 1.2 ns (+Ca2+), values that are smaller than the
      principal correlation times determined for the global rotation of the free
      calmodulin monomer in either the presence or absence of Ca2+. The
      intermolecularly cross-linked segments of the polymers retain a degree of the
      mobility that is characteristic of the tyrosine-containing sequences of native
      calmodulin. The half-widths of the normal distribution curves range from 13 ns
      (zero Ca2+) to approximately 90 ns (5 mM Ca2+), thus encompassing varying rates
      of segmental motion within the polymers. When Ca2+ is present, possible
      contributions from the global rotations of polymer molecules are detected near
      the operating limits of the method. Experiments with the intramolecularly cross
      linked calmodulin monomer give global rotational correlation times of 7.9 ns
      (zero Ca2+) and 11.4 ns (+Ca2+), which compare to values of 7.2 ns and 9.9 ns
      found previously in time domain measurements [Small, E. W., and Anderson, S. R.
      (1988) Biochemistry 27, 419]. Rotations of apparent phi2 = 0.2 to 0.3 ns also are
      detected, accounting for 31% (-Ca2+) to 23% (+Ca2+) of the anisotropy.

PMID- 9622490
TI  - Effect of ATP analogues on the actin-myosin interface.
AB  - The interaction between skeletal myosin subfragment 1 (S1) and filamentous actin
      was examined at various intermediate states of the actomyosin ATPase cycle by
      chemical cross-linking experiments. Reaction of the actin-S1 complex with 1-ethyl
      3-[3-(dimethylamino)propyl]carbodiimide and N-hydroxysuccinimide generated
      products with molecular masses of 165 and 175 kDa, in which S1 loops of residues
      626-647 and 567-578 were cross-linked independently to the N-terminal segment of
      residues 1-12 of one actin monomer, and of 265 kDa, in which the two loops were
      bound to the N termini of two adjacent monomers. In strong-binding complexes,
      i.e., without nucleotide or with ADP, S1 was sequentially cross-linked to one and
      then to two actin monomers. In the weak-binding complexes, two types of cross
      linking pattern were observed. First, during steady-state hydrolysis of ATP or
      ATPgammaS at 20 degreesC, the cross-linking reaction gave rise to a small amount
      of unknown 200 kDa product. Second, in the presence of AMPPNP, ADP.BeFx, ADP.AlF4
      , or ADP.VO43- or with S1 internally cross-linked by N,N'-p-phenylenedimaleimide,
      only the 265 kDa product was obtained. The presence of 200 mM salt inhibited
      cross-linking reactions in both weak- and strong-binding states, while it
      dissociated only weak-binding complexes. These results indicate that, in the weak
      binding state populated with the ADP.Pi analogues, skeletal S1 interacts
      predominantly and with an apparent equal affinity with the N termini of two
      adjacent actin monomers, while these ionic contacts are much less significant in
      stabilizing the rigor actin-S1 complexes. They also suggest that the
      electrostatic actin-S1 interface is not influenced by the type of ADP.Pi analogue
      bound to the active site.

PMID- 9622491
TI  - Tubulin polyglutamylase: partial purification and enzymatic properties.
AB  - In this work, we report on a novel enzyme, tubulin polyglutamylase, which
      catalyzes the posttranslational formation of polyglutamyl side chains onto alpha-
      and beta-tubulin. The length of the polyglutamyl side chain regulates the
      interaction between tubulin and various microtubule-associated proteins. We first
      developed an in vitro glutamylation assay. Activity measured in brain, a tissue
      particularly enriched with glutamylated tubulin, decreases during postnatal
      development. Thus, brains from 3-day-old mice were chosen as the starting
      material, and the enzyme was purified approximately 1000-fold. Its Mr was
      estimated to be 360K and its sedimentation coefficient 10 s. The enzyme catalyzes
      the MgATP-dependent addition of l-glutamate onto tubulin subunits. Microtubules
      are much better substrates than unpolymerized tubulin, and the reaction is very
      specific for glutamate, other amino acids or glutamate analogues not being
      substrates. Moreover, glutamyl units are added sequentially onto tubulin, leading
      to progressive elongation of the polyglutamyl side chains. Side chains of one to
      six or seven glutamyl units were obtained with microtubules, whereas much longer
      side chains (up to 15-20 units) were formed with unpolymerized tubulin.
      Interestingly, such very long polyglutamyl side chains were recently detected in
      some situations in vivo.

PMID- 9622492
TI  - Modulation of the redox potentials of FMN in Desulfovibrio vulgaris flavodoxin:
      thermodynamic properties and crystal structures of glycine-61 mutants.
AB  - Mutants of the electron-transfer protein flavodoxin from Desulfovibrio vulgaris
      were made by site-directed mutagenesis to investigate the role of glycine-61 in
      stabilizing the semiquinone of FMN by the protein and in controlling the flavin
      redox potentials. The spectroscopic properties, oxidation-reduction potentials,
      and flavin-binding properties of the mutant proteins, G61A/N/V and L, were
      compared with those of wild-type flavodoxin. The affinities of all of the mutant
      apoproteins for FMN and riboflavin were less than that of the wild-type
      apoprotein, and the redox potentials of the two 1-electron steps in the reduction
      of the complex with FMN were also affected by the mutations. Values for the
      dissociation constants of the complexes of the apoprotein with the semiquinone
      and hydroquinone forms of FMN were calculated from the redox potentials and the
      dissociation constant of the oxidized complex and used to derive the free
      energies of binding of the FMN in its three oxidation states. These showed that
      the semiquinone is destabilized in all of the mutants, and that the extent of
      destabilization tends to increase with increasing bulkiness of the side chain at
      residue 61. It is concluded that the hydrogen bond between the carbonyl of
      glycine-61 and N(5)H of FMN semiquinone in wild-type flavodoxin is either absent
      or severely impaired in the mutants. X-ray crystal structure analysis of the
      oxidized forms of the four mutant proteins shows that the protein loop that
      contains residue 61 is moved away from the flavin by 5-6 A. The hydrogen bond
      formed between the backbone nitrogen of aspartate-62 and O(4) of the
      dimethylisoalloxazine of the flavin in wild-type flavodoxin is absent in the
      mutants. Reliable structural information was not obtained for the reduced forms
      of the mutant proteins, but if the mutants change conformation when the flavin is
      reduced to the semiquinone, to facilitate hydrogen bonding between N(5)H and the
      carbonyl of residue 61, then the change must be different from that known to
      occur in wild-type flavodoxin.

PMID- 9622493
TI  - Plant polyketide synthases: a chalcone synthase-type enzyme which performs a
      condensation reaction with methylmalonyl-CoA in the biosynthesis of C-methylated
      chalcones.
AB  - Heterologous screening of a cDNA library from Pinusstrobus seedlings identified
      clones for two chalcone synthase (CHS) related proteins (PStrCHS1 and PStrCHS2,
      87.6% identity). Heterologous expression in Escherichia coli showed that PStrCHS1
      performed the typical CHS reaction, that it used starter CoA-esters from the
      phenylpropanoid pathway, and that it performed three condensation reactions with
      malonyl-CoA, followed by the ring closure to the chalcone. PstrCHS2 was
      completely inactive with these starters and also with linear CoA-esters. Activity
      was detected only with a diketide derivative (N-acetylcysteamine thioester of 3
      oxo-5-phenylpent-4-enoic acid) that corresponded to the CHS reaction intermediate
      postulated after the first condensation reaction. PstrCHS2 performed only one
      condensation, with 6-styryl-4-hydroxy-2-pyrone derivatives as release products.
      The enzyme preferred methylmalonyl-CoA against malonyl-CoA, if only methylmalonyl
      CoA was available. These properties and a comparison with the CHS from Pinus
      sylvestris suggested for PstrCHS2 a special function in the biosynthesis of
      secondary products. In contrast to P. sylvestris, P. strobus contains C
      methylated chalcone derivatives, and the methyl group is at the position
      predicted from a chain extension with methylmalonyl-CoA in the second
      condensation of the biosynthetic reaction sequence. We propose that PstrCHS2
      specifically contributes the condensing reaction with methylmalonyl-CoA to yield
      a methylated triketide intermediate. We discuss a model that the biosynthesis of
      C-methylated chalcones represents the simplest example of a modular polyketide
      synthase.

PMID- 9622494
TI  - Kinetic isotope effects as probes of the mechanism of galactose oxidase.
AB  - Galactose oxidase (GO) is a member of the family of radical-coupled copper
      oxidases, enzymes containing a free radical coordinated to copper in the active
      site. In catalysis GO cycles between an oxidized state (comprising Cu(II) with a
      unique cysteinyl-tyrosine radical) and a reduced state (comprising Cu(I) with the
      singlet cysteinyl-tyrosine) as it catalyzes the two-electron oxidation of
      alcohols to aldehydes and the subsequent reduction of O2 to H2O2. A ping-pong
      mechanism involving radical intermediates has been proposed for GO catalysis.
      Previous steady-state kinetics studies have demonstrated a KIE of 7-8 that was
      attributed to substrate oxidation, a process involving the stereospecific
      abstraction of the pro-S hydrogen from the 6-hydroxymethyl group of galactose. We
      have used rapid kinetics methods to measure the anaerobic reduction of GO
      substrate at 4 degreesC and carry out enzyme-monitored turnover experiments using
      6-protio and 6-deutero substrates, both in H2O and D2O. At concentrations below
      Km, the apparent second-order rate constant for protio-substrate oxidation, kred,
      was 1.59 x 10(4) M-1 s-1, while that for deuterated substrate was 7.50 x 10(2) M
      1 s-1, a KIE of 21.2. Steady-state measurements of oxygen consumption at low
      galactose concentrations reveal an unusually large isotope effect (kH/kD = 22.5
      +/- 2) for oxidation of 1-O-methyl-6, 6'-di-[2H]-alpha-d-galactopyranoside, and
      at high galactose concentrations, where the oxygen half-reaction is rate-limiting
      in catalysis, a surprisingly large KIE (kH/kD = 8 +/- 1) for the reduction of O2
      to H2O2. There is no detectable solvent isotope effect (<5%) on any of these
      measurements. This shows that there are no exchangeable protons involved in any
      kinetically significant step and that the hydrogen atom removed from galactose is
      not lost to solvent during catalysis; instead, it also participates in the rate
      limiting step of the subsequent reaction with oxygen. At concentrations below Km,
      apparent second-order rate constants for protio-substrate oxidation (kred = 1.5 x
      10(4) M-1 s-1) and O2 reduction (kox = 8 x 10(6) M-1 s-1) have been estimated
      from measurements both by steady-state oxygen electrode and by enzyme-monitored
      turnover. This is completely consistent with the anaerobic studies mentioned
      above. Our results show that the enzyme is essentially fully oxidized while in
      steady-state turnover, consistent with the reduction step being nearly fully rate
      limiting at practical substrate concentrations, due to the very fast reaction
      with physiological concentrations of O2. Overall, the catalytic reaction is in
      concordance with a ping-pong mechanism. The large KIE associated with reduction
      of the enzyme in all three methods appears to reflect hydrogen atom radical
      abstraction by the active site tyrosine radical in the rate-determining step, in
      agreement with the previously proposed radical mechanism for GO. The KIE
      determined at low substrate concentrations (where oxidation of substrate is rate
      determining) from steady-state oxygen consumption measurements, varies from 22.5
      at 4 degreesC to 13 at 45 degreesC, consistent with tunneling being involved in
      the hydrogen atom transfer step.

PMID- 9622495
TI  - Protonic equilibria in the reductive half-reaction of the medium-chain acyl-CoA
      dehydrogenase.
AB  - Oxidation of thioester substrates in the medium-chain acyl-CoA dehydrogenase
      involves alpha-proton abstraction by the catalytic base, Glu376, with transfer of
      a beta-hydride equivalent to the flavin prosthetic group. Polarization of bound
      acyl-CoA derivatives by the recombinant human liver enzyme has been studied with
      4-thia-trans-2-enoyl-CoA analogues. Polarization is maximal at low pH, with an
      apparent pK of 9.2 for complexes with the C8 analogue, and progressively lower pK
      values as the length of the chain increases. This pH effect reflects ionization
      of the catalytic base, since polarization of a variety of enoyl-CoA analogues by
      the Glu376Gln mutant is pH independent. Binding of these ligands is accompanied
      by uptake of about 1 proton with the wild-type enzyme, but only about 0.1 proton
      with the Glu376Gln mutant. Rapid reaction studies show that proton uptake with
      the wild-type enzyme occurs at the same rate as polarization of the enoyl-CoA
      thioester, but is much slower than the initial ligand binding step. Studies with
      6-OH-FAD-substituted enzyme show that this isomerization reaction also influences
      the flavin prosthetic group inducing deprotonation to the green anionic form. The
      failure of the bound thioether analogue, octyl-SCoA, to elicit pK shifts to
      flavin and Glu376 shows the importance of the thioester carbonyl oxygen in
      modulating key properties of the medium-chain enzyme. The role of thioester
      mediated desolvation within the active site of the acyl-CoA dehydrogenases is
      discussed.

PMID- 9622496
TI  - Discriminatory influence of Glu-376-->Asp mutation in medium-chain acyl-CoA
      dehydrogenase on the binding of selected CoA-ligands: spectroscopic,
      thermodynamic, kinetic, and model building studies.
AB  - We investigated the influence of Glu-376-->Asp (E376D) mutation on the UV/visible
      spectral, thermodynamic, and kinetic properties for the interaction of
      structurally different types of CoA-ligands (viz., octenoyl-CoA, acetoacetyl-CoA,
      and indoleacryloyl-CoA) to human liver medium-chain acyl-CoA dehydrogenase
      (MCAD). Whereas the E376D mutation had minimal/negligible effect on the above
      properties for the binding of octenoyl-CoA to the enzyme, it had pronounced
      effects (albeit in opposite directions) for the binding of acetoacetyl-CoA and
      indoleacryloyl-CoA to the enzyme. In the case of acetoacetyl-CoA, the spectrum of
      the enzyme-ligand complex (in the charge-transfer region; lambdamax = 545 nm) was
      1.8-fold more pronounced, and the DeltaH degrees value for the binding of
      acetoacetyl-CoA to the enzyme was 5.6 kcal/mol more favorable with wild-type as
      compared to the E376D mutant enzyme. The kinetic data revealed that the above
      effects were related to an increase in the dissociation "off-rate" of acetoacetyl
      CoA from the enzyme-acetoacetyl-CoA complex. In contrast, in the case of IACoA,
      the resultant UV/visible spectrum of the enzyme-IACoA complex (lambdamax = 416
      nm) was 2.7-fold less pronounced, and the DeltaH degrees value of the enzyme
      IACoA complex was 6.4 kcal/mol less favorable with the wild-type than the E376D
      mutant enzyme. The latter effects were supported by the fact that the above
      mutation impaired the dissociation "off-rate" of IACoA from the enzyme-IACoA
      complex by 5.7-fold. Molecular model building studies revealed that the
      discriminatory influence of the E376D mutation on the spectral, thermodynamic,
      and kinetic properties of the enzyme-ligand complexes is due to ligand-specific
      changes in the spatial relationship between the FAD and CoA-ligands at the enzyme
      site. Arguments are presented that the "void" created by excision of a methylene
      group from Glu-376 (upon Glu-376-->Asp mutation) is adjusted differently upon
      interaction with structurally different types of CoA-ligands.

PMID- 9622497
TI  - Bovine serum fetuin is unfolded through a molten globule state.
AB  - The reversible heat- and GuHCl-induced unfolding of bovine serum fetuin (BSF) has
      been studied by differential scanning calorimetry, circular dicroism, tryptophan
      fluorescence, and size-exclusion chromatography. We show here that thermal
      unfolding of BSF occurs in two distinct steps corresponding to transitions from
      the native (N) to an intermediate (I) and from the intermediate to the unfolded
      state (U). The Nleft and right arrow I transition is highly cooperative and can
      well be accounted for by a two-state mechanism. The Ileft and right arrow U
      transition is also cooperative but to a lesser extent than the Nleft and right
      arrow I transition. CD spectra show that the protein in the I state retains
      nearly all of the native secondary structure and has a largely disrupted tertiary
      structure. However, the hydrophobic environment of the single tryptophan residue
      is not changed, and some compactness is retained in the I state. The structural
      properties of this intermediate state are apparently characteristic of a molten
      globule. The GuHCl-induced unfolding is also a two-step process with an I state
      around 2 M GuHCl. Although the structural features of the denaturant-induced I
      state are somewhat different from those of the heat-induced I state, the
      unfolding free energies DeltaG degreesNleft and right arrow I and DeltaG
      degreesIleft and right arrow U as well as DeltaG degreesNleft and right arrow U
      obtained from these two methods are comparable. We argue that the observed two
      state Nleft and right arrow I transition is due to the melting of the tertiary
      packing, while leaving quasi-intact the secondary structure and some long-range
      interactions in the I state. These long-range interactions, together with the
      secondary structural elements, would be responsible for the observed
      cooperativity of the Ileft and right arrow U transition.

PMID- 9622498
TI  - Unfolding of the tetrameric loop deletion mutant of ROP protein is a second-order
      reaction.
AB  - Comprehensive kinetic studies were carried out on the unfolding properties of RM6
      as a function of GdnHCl concentration and temperature. This protein is a mutant
      resulting from the dimeric wild-type CoLE1-ROP protein by deletion of 5 amino
      acids (Asp 30, Ala 31, Asp 32, Glu 33, Gln 34) in the loop of each monomer. The
      deletion has dramatic consequences. The dimeric 4-alpha-helix structure
      characteristic of the wild-type protein is completely reorganized and the RM6
      structure can be described as a tetrameric alpha helix of extended monomers
      without loops. These extraordinary structural changes are accompanied by an
      enormous increase in transition temperature from 71 to 101 degreesC. These
      features have been discussed in a separate publication (1). The remarkable change
      in thermal stability of RM6 should be reflected in significant changes in the
      folding rate constants. This was observed in the present unfolding studies. Decay
      of tetrameric RM6 was monitored by circular dichroism (CD) and fluorescence to
      probe for changes in both secondary and tertiary structure, respectively. The
      identity of the kinetic parameters obtained from the two techniques supports the
      view that secondary and tertiary structure break down simultaneously. However,
      the most intriguing result is the finding that unfolding of tetrameric RM6 can be
      described very well by a second-order reaction. The magnitude of the second-order
      rate constant k2 varies dramatically with both temperature and denaturant
      concentration. At 25 degreesC and 6.5 M GdnHCl concentration k2 is 4200 L.(mol of
      dimer)-1.s-1, whereas at 4.4 M GdnHCl a value of k2 = 0.9 L.(mol of dimer)-1.s-1
      is observed. Correspondingly, apparent activation enthalpies show a strong
      increase from DeltaH# = 29.1 kJ.mol-1 at 6. 5 M GdnHCl to Delta H# = 79.7 kJ.mol
      1 at 4.4 M GdnHCl. A mechanism involving a dimeric intermediate is suggested
      which permits a consistent interpretation of the findings.

PMID- 9622499
TI  - Characterization of collapsed states in the early stages of the refolding of hen
      lysozyme.
AB  - Early conformational states in the refolding of hen lysozyme from guanidine
      hydrochloride have been characterized by measuring both the fluorescence and the
      solvent exchange properties of tryptophan side chains. The indole proton
      occupancies indicate that at pH 5.5, 25 degrees C, half the protection against
      pulse labeling occurs in the dead time (4 ms) of the experiment, with the
      remaining protection developing with a time constant of 55 ms. Comparison of
      these data with the protection kinetics of backbone amides and with the
      fluorescence data provides evidence for hydrophobic collapse involving
      incorporation of tryptophan residues in a solvent-excluded state in advance of
      stable secondary structure formation. Analysis of the pH dependence of the indole
      hydrogen exchange protection is consistent with two or more structurally distinct
      collapsed states, and indicates that the generation of a correctly folded compact
      hydrophobic core is a key precursor to the formation of persistent native-like
      structure during refolding.

PMID- 9622501
TI  - Ga3+ as a functional substitute for Fe3+: preparation and characterization of the
      Ga3+Fe2+ and Ga3+Zn2+ forms of bovine spleen purple acid phosphatase.
AB  - A general method has been developed that allows the specific substitution of both
      iron atoms in the enzyme bovine spleen purple acid phosphatase (BSPAP), which
      possesses a dinuclear iron center at the active site. The approach is
      demonstrated by the preparation and characterization (atomic absorption
      spectrometry, enzyme kinetics, optical spectroscopy, and electron paramagnetic
      resonance spectroscopy) of two metal-substituted forms in which the ferric iron
      has been replaced by Ga3+: Ga3+Fe2+-BSPAP and Ga3+Zn2+-BSPAP. Both forms are
      colorless but exhibit enzymatic activity comparable to that of the native
      Fe3+Fe2+-BSPAP. Small but consistent changes in kinetics parameters and pH
      profiles were detected both upon substitution of Fe3+ by Ga3+ and upon
      substitution of Fe2+ by Zn2+. These results constitute the first evidence that
      the diamagnetic Ga3+ ion can serve as a functional analogue of Fe3+ in an enzyme,
      and suggest a novel approach for the study of the role of Fe3+ in other iron
      enzymes.

PMID- 9622500
TI  - Implication of His68 in the substrate site of Bacillus subtilis adenylosuccinate
      lyase by mutagenesis and affinity labeling with 2-[(4-bromo-2,3
      dioxobutyl)thio]adenosine 5'-monophosphate.
AB  - Adenylosuccinate lyase of Bacillus subtilis is inactivated by 2-[(4-bromo-2,3
      dioxobutyl)thio]adenosine 5'-monophosphate (2-BDB-TAMP) at pH 7.0. As the reagent
      concentration is increased, a maximum rate constant is approached, indicative of
      reversible enzyme-reagent complex formation (KR = 68 +/- 9 microM) prior to
      irreversible modification (kmax = 0.081 +/- 0.004 min-1). Complete inactivation
      occurs concomitant with about 1 mol of 2-BDB-[14C]TAMP incorporated/mol of enzyme
      subunit. Adenylosuccinate, or a combination of AMP and fumarate, decreases the
      inactivation rate and reduces incorporation of [14C] reagent, whereas either AMP
      or fumarate alone is much less effective. These observations suggest that 2-BDB
      TAMP attacks the adenylosuccinate binding site. Proteolytic digestion of
      inactivated enzyme, followed by purification of the digest by HPLC, yields the
      radioactive peptide Ile62-Ala72, in which Arg67 and His68 are the most likely
      targets. Thus 2-BDB-TAMP reacts with adenylosuccinate lyase at a site distinct
      from the His141 attacked by 6-BDB-TAMP (Lee, Worby, Dixon, and Colman (1997) J.
      Biol. Chem. 272, 458-465). Site-directed mutagenesis was used to construct mutant
      enzymes with replacements for both Arg67 and His68, and either Arg67 or His68.
      The R67M mutant enzyme has almost the same specific activity as the wild-type
      enzyme under standard assay conditions, whereas the single mutant H68Q and double
      mutant R67M-H68Q enzymes exhibit specific activities that are decreased more than
      100-fold. These results indicate that while Arg67 and His68 may both be in the
      region of the substrate site, only His68 is important for the catalytic activity
      of B. subtilis adenylosuccinate lyase. A role is proposed for His68 as a general
      acid-base catalyst.

PMID- 9622502
TI  - In vitro disulfide-coupled folding of guanylyl cyclase-activating peptide and its
      precursor protein.
AB  - Guanylyl cyclase-activating peptide II (GCAP-II), an endogenous ligand of
      particulate guanylyl cyclase C (GC-C), is processed from the precursor protein
      and circulates in human blood. GCAP-II consists of 24 amino acid residues and
      contains two disulfide bridges. The correct disulfide paring of GCAP-II is an
      absolute requirement for its biological activity. This study shows that the
      folding of the peptide from the reduced form yields a peptide with the native
      disulfide paring as a minor product and with non-native ones as major products,
      regardless of the presence or absence of reduced and oxidized glutathione. The
      results suggest that GCAP-II does not possess sufficient information to permit
      the adoption of the native conformation and to effectively form the correct
      disulfide pairing and, as a result, that GCAP-II is correctly folded by
      assistance of a factor(s) such as an intra- or intermolecular chaperone. We
      studied whether a peptide in the pro-leader sequence of the precursor protein
      (proGCAP-II) contains sufficient information to facilitate the folding of GCAP
      II. For this purpose, we prepared proGCAP-II in Escherichia coli by a recombinant
      technique and examined the disulfide-coupled folding of proGCAP-II from the
      reduced form. proGCAP-II was quantitatively recovered with the correctly folded
      structure from the reduced form both in the presence and in the absence of
      reduced and oxidized glutathione. The protein contains only disulfide linkages at
      the same positions as the mature form of proGCAP-II, GCAP-II, and the
      biologically active isomer of GCAP-II in the molecule. These results provide
      evidence that the propeptide of proGCAP-II is a critical factor in the formation
      of the correct disulfide paring in the folding of the protein.

PMID- 9622503
TI  - Bimodal inhibition of caspase-1 by aryloxymethyl and acyloxymethyl ketones.
AB  - The caspase-1 (interleukin 1beta-converting enzyme; ICE) titrant 3-[2-(2
      benzyloxycarbonylamino-3-methylbutyrylamino) propionylamino]-4 -oxo-5-(2-oxo-2H
      chromen-7-yloxy)pentanoic acid (1 (Dang, L. C., et al. (1996) Biochemistry 35,
      14910-14916)) inhibits caspase-1 activity rapidly, while release of the 7
      hydroxycoumarin fluorophore is much slower. Progress curve analysis of 1 and of
      the related acyloxymethyl ketone 3-[2-(2-benzyloxycarbonylamino-3
      methylbutyrylamino) propionylamino]-4 -oxo-5-(1-oxo-3-phenylpropoxy)pentanoic
      acid (2) identifies distinctive residual patterns which are caused by the
      superimposition of potent slow-binding reversible inhibition with slower,
      irreversible inactivation. Standard kinetic models are not entirely adequate for
      analysis of these bimodal inhibitors, but by measuring the kinetic properties of
      these inhibitors by several independent techniques and comparing these to
      simulations which closely mimic the inhibitor actions, careful application of the
      standard models can provide reasonably accurate kinetic constants.

PMID- 9622504
TI  - Calcium-dependent and -independent interfacial binding and catalysis of cytosolic
      group IV phospholipase A2.
AB  - Cytosolic group IV phospholipase A2 (cPLA2) plays a role in liberating
      arachidonic acid from the sn-2 position of mammalian cellular phospholipids. The
      enzyme consists of a catalytic domain joined to an N-terminal calcium-dependent,
      membrane binding domain (C2 domain). The interfacial binding properties of the
      full-length, nonphosphorylated enzyme and its C2 domain to phospholipid vesicles
      were studied as a function of vesicle phospholipid composition and calcium
      concentration. The binding of cPLA2 to phosphatidylcholine vesicles is mostly
      governed by its C2 domain; binding is relatively weak, and calcium enhances
      binding and interfacial catalysis by about 10-fold. Catalytically productive
      interfacial binding was measured by monitoring the increase in the rate of cPLA2
      catalyzed hydrolysis of a fluorimetric substrate present in vesicles as a
      function of bulk vesicle concentration. Enzyme-vesicle binding was also measured
      by fluorescence as was enzyme-calcium binding. Compared to zwitterionic vesicles,
      cPLA2 binding to anionic phosphatidylmethanol vesicles is of higher affinity and
      calcium-independent, although calcium is required for the binding of the C2
      domain to these anionic vesicles. cPLA2 is fully catalytically active on
      phosphatidylmethanol vesicles in the absence of calcium. Phosphatidylserine is
      not a good replacement for phosphatidylmethanol for inducing high-affinity,
      calcium-independent binding of cPLA2. These results reveal two modes of
      catalytically productive interfacial binding of cPLA2: calcium-dependent
      anchoring via the C2 domain and a calcium-independent component involving a
      phosphatidylmethanol recognition element in the catalytic domain. They also show
      that membrane binding of cPLA2 is not, in general, predicted by the interfacial
      binding properties of its C2 domain.

PMID- 9622505
TI  - Solution structure of the cytoplasmic domain of the human CD4 glycoprotein by CD
      and 1H NMR spectroscopy: implications for biological functions.
AB  - The human T cell receptor CD4 is a type I integral membrane glycoprotein that is
      involved in T cell activation and also acts as the primary coreceptor for human
      immunodeficiency viruses (HIV). Here the structure of a synthetic 38 amino acid
      peptide corresponding to the complete cytoplasmic domain of CD4 (CD4CYTO) has
      been investigated under a variety of solution conditions using a combination of
      circular dichroism and homonuclear two-dimensional 1H nuclear magnetic resonance
      spectroscopy. In the presence of the membrane mimetic 2,2,2-trifluoroethanol
      (TFE), a conformational change of CD4CYTO from a random coil to an alpha-helical
      structure was observed. In keeping with this, CD4CYTO has the potential to
      associate with membranes as demonstrated by binding studies of in vitro
      phosphorylated CD4CYTO with microsomal membranes. Both chemical shift and nuclear
      Overhauser enhancement data in 50% 2,2, 2-trifluoroethanol solution provide
      direct experimental evidence for the predominance of a short amphiphatic alpha
      helix that is approximately 4 turns in length and extends from positions Arg-402
      to Lys-417. The present data provide, for the first time, compelling experimental
      evidence that only a fraction of CD4CYTO has a propensity for adopting secondary
      structure under conditions that are assumed to exist at or near to the membrane
      surface and that this alpha-helical structure is located in the membrane-proximal
      region of CD4CYTO. The N-terminal residues, that link the alpha-helix to the
      transmembrane anchor of CD4, and a substantial C-terminal portion (14-18
      residues) of CD4CYTO are unstructured under the solution conditions investigated.
      Correlation of our structural data with recent studies on the biological activity
      of CD4CYTO indicates that the alpha-helix is of crucial importance for the
      interaction of CD4 with Nef and Vpu in the process of HIV-mediated CD4 down
      regulation.

PMID- 9622506
TI  - L-arginine binding to liver arginase requires proton transfer to gateway residue
      His141 and coordination of the guanidinium group to the dimanganese(II,II)
      center.
AB  - Rat liver arginase contains a dimanganese(II,II) center per subunit that is
      required for catalytic hydrolysis of l-arginine to form urea and l-ornithine. A
      recent crystallographic study has shown that the Mn2 center consists of two
      coordinatively inequivalent manganese(II) ions, MnA and MnB, bridged by a water
      (hydroxide) molecule and two aspartate residues [Kanyo et al. (1996) Nature 383,
      554-557]. A conserved residue, His141, is located near the proposed substrate
      binding region at 4.2 A from the bridging solvent molecule. The present EPR
      studies reveal that there is no essential alteration of the Mn2 site upon
      mutation of His141 to an Asn residue, which lacks a potential acid/base residue,
      while the catalytic activity of the mutant enzyme is 10 times lower vs wild-type
      enzyme. The binding affinity of l-lysine, l-arginine (substrate), and Nomega-OH-l
      arginine (type 2 binders) increases inversely with the pKa of the side chain.
      Binding of l-lysine is more than 10 times weaker, and the substrate Michaelis
      constant (Km) is >6-fold greater (weaker binding) in the His141Asn mutant than in
      wild-type arginase. L-Lysine and Nomega-OH-L-arginine, type 2 binders, induce
      extensive loss of the EPR intensity, suggesting direct coordination to the Mn2
      center. From these data and the pH dependence of type 2 binders, we conclude that
      His141 functions as the base for deprotonation of the side-chain amino group of L
      lysine and the substrate guanidinium group, -NH-C(NH2)2+ and that the
      unprotonated side chain of these amino acids is responsible for binding to the
      active site. A different class of inhibitors (type 1), including L-isoleucine, L
      ornithine, and L-citrulline, suppresses enzymatic activity, producing only minor
      change in the zero-field splitting of the Mn2 EPR signal and no change in the EPR
      intensity, suggestive of minimal conformational transformation. We propose that
      type 1 alpha-amino acid inhibitors do not bind directly to either Mn ion, but
      interact with the recognition site on arginase for the alpha-aminocarboxylate
      groups of the substrate. A new mechanism for the arginase-catalyzed hydrolysis of
      L-arginine is proposed which has general relevance to all binuclear hydrolases:
      (1) Deprotonation of substrate l-arginine(H+) by His141 permits entry of the
      neutral guanidinium group into the buried Mn2 region. Binding of the substrate
      imino group (>C=NH), most likely to MnB, is coupled to breaking of the MnB-(mu
      H2O) bond, forming a terminal aquo ligand on MnA. (2) Proton transfer from the
      terminal MnA-aqua ligand to the substrate Ndelta-guanidino atom forms the
      nucleophilic hydroxide on MnA and the cationic NdeltaH2+-guanidino leaving group.
      Protonation of the substrate -NdeltaH2+-group is likely assisted by hydrogen
      bonding to the juxtaposed anionic carboxylate group of Glu277. (3) Attack of the
      MnA-bound hydroxide at the electrophilic guanidino C-atom forms a tetrahedral
      intermediate. (4) Formation of products is initiated by cleavage of the Cepsilon
      NdeltaH2+ bond, yielding urea and L-ornithine(H+).

PMID- 9622507
TI  - Anion activation of 3-phosphoglycerate kinase requires domain closure.
AB  - 3-Phosphoglycerate kinase is a typical two-domain "hinge-bending" enzyme, which
      is known to be regulated by multivalent anions. Here a relationship between this
      regulation and the hinge-bending domain closure is proposed on the basis of
      enzyme kinetic analysis and molecular modeling. Activation of the pig muscle
      enzyme at low concentrations and inhibition at high concentrations of various
      anionic analogues of the substrate 3-phosphoglycerate or of the nonsubstrate
      metal-free ATP are described by a two-site model assuming separate sites for
      activation and inhibition, respectively. Kinetic experiments with various pairs
      of analogues suggest the presence of a common site for activation by all
      effectors, separate from the catalytic site for 3-phosphoglycerate; and a common
      site for inhibition, except for metal-free ATP, identical with the catalytic site
      of 3-phosphoglycerate. An additional inhibiting site for all of the anions
      investigated, including metal-free ATP, is also proposed. A similar two-site
      model can describe activation of the enzyme by a large excess of each substrate;
      here the ligand binds to the catalytic site as a substrate and to the regulatory
      site as an activator. Activation is exerted not only by the physiological
      substrate, 3-phophoglycerate, but also by a synthetic weak substrate. The
      activity in the reaction with 3-phosphoglycerate and MgATP is greatly enhanced by
      the simultaneous presence of the weak substrate. This finding clearly proves the
      existence of a regulatory site, separate from the catalytic site. This regulatory
      site, however, may only exist in the catalytically competent closed conformation
      of the enzyme, as indicated by molecular modeling. Docking of the regulator
      anions into the known X-ray structures of the enzyme revealed the appearance of
      an anion binding site between the two domains, including the invariant residues
      of Lys-215 (C-domain) and of Arg-65 among other residues of the basic cluster (N
      domain), as a consequence of the large-scale substrate-induced conformational
      change that leads to domain closure.

PMID- 9622508
TI  - Recognition of capped RNA substrates by VP39, the vaccinia virus-encoded mRNA cap
      specific 2'-O-methyltransferase.
AB  - We have investigated the interaction of VP39, the vaccinia-encoded mRNA cap
      specific 2'-O-methyltransferase, with its capped RNA substrate. Two sites on the
      protein surface, responsible for binding the terminal cap nucleotide (m7G) and
      cap-proximal RNA, were characterized, and a third (downstream RNA binding) site
      was identified. Regarding the crystallographically defined m7G binding pocket,
      VP39 showed significant activity with adenine-capped RNA. Although VP39 mutants
      lacking specific m7G-contact side chains within the pocket showed reduced
      catalytic activity, none was transformed into a cap-independent RNA
      methyltransferase. Moreover, each retained a preference for m7G and A over
      unmethylated G as the terminal cap nucleotide, indicating a redundancy of m7G
      contact residues able to confer cap-type specificity. Despite containing the 2'-O
      methylation site, m7GpppG (cap dinucleotide) could not be methylated by VP39, but
      m7GpppGUbiotinp could. This indicated the minimum-length 2'-O-methyltransferase
      substrate to be either m7GpppGp, m7GpppGpN, or m7GpppGpNp. RNA-protein contacts
      immediately downstream of the m7GpppG moiety were found to be pH-sensitive. This
      was detectable only in the context of a weakened interaction of near-minimum
      length substrates with VP39's m7G binding pocket (through the use of either
      adenine-capped substrate or a VP39 pocket mutant), as a dramatic elevation of KM
      at pH values above 7.5. KM values for substrates with RNA chain lengths of 2-6 nt
      were between 160 and 230 nM, but dropped to 9-15 nM upon increasing chain lengths
      to 20-50 nt. This suggested the binding of regions of the RNA substrate >6 nt
      from the 5' terminus to a previously unknown site on the VP39 surface.

PMID- 9622509
TI  - Effect of mismatched complementary strands and 5'-change in sequence context on
      the thermodynamics and structure of benzo[a]pyrene-modified oligonucleotides.
AB  - Benzo[a]pyrene (B[a]P) is a well-studied environmental carcinogen that when
      activated can react with DNA to form four major adducts: (+)-trans-, (-)-trans-,
      (+)-cis-, and (-)-cis-anti-B[a]P-dG. In this study, two oligonucleotides (5'
      dCCATT-GB[a]P-CTACC-3' and 5'-dCCATC-GB[a]P-CTACC-3') were prepared, each
      containing the four isomeric adducts, and these were hybridized to either
      complementary sequences or to sequences containing an A, G, or T opposite the
      adducted guanine. Thermal melting curves, CD, and UV spectra of each duplex were
      measured and compared with the unmodified counterpart. The raw and relative
      thermodynamic measurements were then compared which indicated that differences
      occur that are both adduct and sequence dependent. These differences were next
      compared with the in vitro DNA polymerase incorporation data and were found to be
      strikingly correlated. Most significantly, for all four B[a]P isomers a mismatch
      of an A across from the adduct resulted in the least amount of relative
      destabilization, while the Watson-Crick complement C showed the most; in vitro
      studies showed that A is the preferred base incorporated across from each isomer,
      while C was incorporated least often. This observed correlation suggests that one
      factor contributing to misincorporation at an adduct site is the thermodynamic
      stability of the incorporated base. Structurally, the effect of sequence context
      and mismatched complementary strands were also compared, suggesting that all
      adducts tend to intercalate within the helix when they are complemented with a
      mismatched complementary strand. In addition, the level of this intercalation
      seems to be both sequence and stereoisomer dependent.

PMID- 9622510
TI  - Involvement of carboxy-terminal amino acids in secretion of human lysosomal
      protease cathepsin L.
AB  - Cathepsin L, a lysosomal cysteine protease, is overexpressed and secreted by
      malignantly transformed cells. However, the reason for secretion of this man 6
      phosphate-containing lysosomal protease into the extracellular medium is not
      clear. We wished to determine whether there is a region within the primary
      sequence of the proenzyme form of cathepsin L which affects its subcellular and
      extracellular localization. High-level transient expression of human procathepsin
      L in mouse NIH 3T3 cells results in the secretion of most of this protein into
      the extracellular medium. At the same time, the endogenous mouse procathepsin L
      in these nontransformed cells is found in its usual location in lysosomes.
      Mutants of human procathepsin L with carboxy-terminus deletions involving the
      last 11 amino acids are not secreted into the medium. Deletion of as little as
      two amino acids, Thr and Val, from the carboxy terminus, blocked the secretion of
      the protein but did not affect its enzyme activity, posttranslational processing,
      or subcellular distribution. Replacement of Thr-Val by two bulky amino acids Tyr
      Asn allowed secretion of the procathepsin L, but the replacement of these two
      amino acids by nonbulky alanines prevented its secretion. Single alanine
      substitutions of the last six amino acids (ASYPTV) indicated that substitution by
      alanine of Y or T does not affect the secretion of hproCAT L, but alanine
      substitutions of S, P, or V completely blocked its secretion into the culture
      medium. We therefore conclude that the carboxy terminus of procathepsin L
      contains a sequence essential for its secretion.

PMID- 9622511
TI  - S-state dependence of chloride binding affinities and exchange dynamics in the
      intact and polypeptide-depleted O2 evolving complex of photosystem II.
AB  - The Cl- binding properties in the successive oxidation states of the O2 evolving
      complex of photosystem II were investigated by measurements of UV absorbance
      changes, induced by a series of saturating flashes, that monitor manganese
      oxidation state transitions. In dark-adapted, intact photosystem II, Cl- can be
      replaced by NO3- in minutes, in an exchange reaction that depends on the NO3-
      concentration and that is not rate-limited by dissociation of Cl- from its
      binding site. Preillumination of dark-adapted photosystem II by one or two
      flashes accelerated the NO3- substitution reaction by an order of magnitude. A
      quantitative analysis of the Cl- concentration dependence of UV absorbance
      changes, measured in photosystem II preparations depleted of extrinsic 17 and 23
      kDa polypeptides, shows that the Cl- binding properties of photosystem II change
      with the oxidation state of the oxygen evolving complex. Although the affinity
      for the individual S-states could not be determined with precision, it is shown
      that the affinity is an order of magnitude lower in the S2 state than in the S1
      state. Comparison of the results obtained using intact photosystem II and
      preparations depleted of the 17 and 23 kDa extrinsic polypeptides suggests that
      these proteins constitute a diffusion barrier, which prevents fast equilibration
      of the Cl- binding site with the medium, but does not change the Cl- affinity of
      the binding site.

PMID- 9622513
TI  - Identification and characterization of a catalytic base in bacterial luciferase
      by chemical rescue of a dark mutant 

PMID- 9622512
TI  - Species-specific differences in the operational RNA code for aminoacylation of
      tRNAPro.
AB  - An operational RNA code relates amino acids to specific structural features
      located in tRNA acceptor stems. In contrast to the universal nature of the
      genetic code, the operational RNA code can vary in evolution due to coadaptations
      of the contacts between aminoacyl-tRNA synthetases and the acceptor stems of
      their cognate tRNA substrates. Here we demonstrate that, for class II prolyl-tRNA
      synthetase (ProRS), functional coadaptations have occurred in going from the
      bacterial to the human enzyme. Analysis of 20 ProRS sequences that cover all
      three taxonomic domains (bacteria, eucarya, and archaea) revealed that the
      sequences are divided into two evolutionarily distant groups. Aminoacylation
      assays showed that, while anticodon recognition has been maintained through
      evolution, significant changes in acceptor stem recognition have occurred.
      Whereas all tRNAPro sequences from bacteria strictly conserve A73 and C1.G72, all
      available cytoplasmic eukaryotic tRNAPro sequences have a C73 and a G1.C72 base
      pair. In contrast to the Escherichia coli synthetase, the human enzyme does not
      use these elements as major recognition determinants, since mutations at these
      positions have only small effects on cognate synthetase charging. Additionally,
      E. coli tRNAPro is a poor substrate for human ProRS, and the presence of the
      human anticodon-D stem biloop domain was necessary and sufficient to confer
      efficient aminoacylation by human ProRS on a chimeric tRNAPro containing the E.
      coli acceptor-TpsiC stem-loop domain. Our data suggest that the two ProRS groups
      may reflect coadaptations needed to accommodate changes in the operational RNA
      code for proline.

PMID- 9622514
TI  - Microfabrication in biology and medicine 

PMID- 9622515
TI  - Micropatterned surfaces for control of cell shape, position, and function.
AB  - The control of cell position and function is a fundamental focus in the
      development of applications ranging from cellular biosensors to tissue
      engineering. Using microcontact printing of self-assembled monolayers (SAMs) of
      alkanethiolates on gold, we manufactured substrates that contained micrometer
      scale islands of extracellular matrix (ECM) separated by nonadhesive regions such
      that the pattern of islands determined the distribution and position of bovine
      and human endothelial cells. In addition, the size and geometry of the islands
      were shown to control cell shape. Traditional approaches to modulate cell shape,
      either by attaching suspended cells to microbeads of different sizes or by
      plating cells on substrates coated with different densities of ECM, suggested
      that cell shape may play an important role in control of apoptosis as well as
      growth. Data are presented which show how micropatterned substrates were used to
      definitively test this hypothesis. Progressively restricting bovine and human
      endothelial cell extension by culturing cells on smaller and smaller
      micropatterned adhesive islands regulated a transition from growth to apoptosis
      on a single continuum of cell spreading, thus confirming the central role of cell
      shape in cell function. The micropatterning technology is therefore essential not
      only for construction of biosurface devices but also for the investigation of the
      fundamental biology of cell-ECM interactions.

PMID- 9622516
TI  - Neurite outgrowth and growth cone morphology on micropatterned surfaces.
AB  - The quantitative effects of micropatterned laminin surfaces on neurite outgrowth
      and growth cone morphology were investigated. Using microlithography, 20- or 30
      micron-wide laminin stripes were applied to the surface of a glass coverslip,
      alternating with BSA-coated glass stripes of the same dimension. Growth on these
      surfaces was strongly biased in the direction parallel to the stripes, but the
      mean length of outgrowth was reduced relative to that on uniform laminin
      surfaces. Growth cones were slightly more elongated on micropatterned surfaces
      than on controls and were aligned with the pattern. These results provide a
      starting point for examining the fundamental effects of micropatterned surfaces
      on neurite outgrowth and ways in which these may be useful in controlling and
      guiding neurite outgrowth for biotechnological applications.

PMID- 9622517
TI  - Computer-controlled laser ablation: a convenient and versatile tool for
      micropatterning biofunctional synthetic surfaces for applications in biosensing
      and tissue engineering.
AB  - This paper describes laser-based methods for preparing micropatterns of bioactive
      molecular species in self-assembled monolayers (SAMs) and micropatterns of
      proteins and other biological molecules immobilized on solid substrates.
      Applications of these micropatterned surfaces in multianalyte biosensing and
      tissue engineering are emphasized. The focus of the paper is on the use of a
      computer-controlled laser ablation system comprising a research-grade inverted
      optical microscope, a pulsed nitrogen-pumped dye laser emitting at 390 nm, a
      programmable sample stage, and the computerized control system. The laser system
      can be implemented in a typical biosensor or tissue culture laboratory to enable
      the facile and reproducible fabrication of micropatterned surfaces by several
      methods. Various methods for patterning are discussed with examples given and
      emphasis placed on (1) laser ablation in the fabrication of photolithography
      masks, (2) electrochemical patterning of SAMs, and (3) laser desorption of SAMs.
      The relative merits of each technique are discussed with respect to application
      in fabrication of active surfaces for biosensing and tissue culture applications.

PMID- 9622518
TI  - Microfabrication of hepatocyte/fibroblast co-cultures: role of homotypic cell
      interactions.
AB  - Cell-cell interactions are important in embryogenesis, in adult physiology and
      pathophysiology of many disease processes. Co-cultivation of parenchymal and
      mesenchymal cells has been widely utilized as a paradigm for the study of cell
      cell interactions in vitro. In addition, co-cultures of two cell types provide
      highly functional tissue constructs for use in therapeutic or investigational
      applications. The inherent complexity of such co-cultures creates difficulty in
      characterization of cell-cell interactions and their effects on function. In the
      present study, we utilize conventional "randomly distributed" co-cultures of
      primary rat hepatocytes and murine 3T3-J2 fibroblasts to investigate the role of
      increasing fibroblast density on hepatic function. In addition, we utilize
      microfabrication techniques to localize both cell populations in patterned
      configurations on rigid substrates. This technique allowed the isolation of
      fibroblast number as an independent variable in hepatic function. Notably,
      homotypic hepatocyte interactions were held constant by utilization of similar
      hepatocyte patterns in all conditions, and the heterotypic interface (region of
      contact between cell populations) was also held constant. Co-cultures were probed
      for synthetic and metabolic markers of liver-specific function. The data suggest
      that fibroblast number plays a role in modulation of hepatocellular response
      through homotypic fibroblast interactions. The response to changes in fibroblast
      number are distinct from those attributed to increased contact between
      hepatocytes and fibroblasts. This approach will allow further elucidation of the
      complex interplay between two cell types as they form a functional model tissue
      in vitro or as they interact in vivo to form a functional organ.

PMID- 9622519
TI  - Cellular micropatterns on biocompatible materials.
AB  - We present a method to produce micropatterns of cells on tissue culture
      substrates. A network of deep elastomeric microchannels defining the desired
      pattern is sealed onto the surface of interest, and a protein template is created
      by injecting sub-milliliter quantities of protein solution into the
      microchannels. Protein adsorbs only on the areas that were exposed to the
      microflow. After the channels are flushed and the elastomer is removed, cells
      attach only on the protein template. Micropatterns of collagen or fibronectin
      were used to selectively adhere cells on various biomedical polymers and on
      heterogeneous or microtextured substrates. Since the bare substrate areas remain
      apt for seeding other, more adhesive cell types such as fibroblasts, we were able
      to create micropatterned co-cultures. Our method allows for inexpensive
      patterning of a rich assortment of biomolecules, cells, and surfaces under
      physiological conditions.

PMID- 9622520
TI  - Effects of oxygen on recombinant protein expression.
AB  - Efforts to increase cell growth and protein yields need to be complemented by the
      maintenance of the quality of the protein produced. Elevated oxygen pressure or
      rapid increases in oxygen content can cause oxidative stress within the cells,
      leading to oxidation of specific proteins and nucleotide sequences. In addition,
      transient or steady-state anoxic conditions can cause limitations in amino acid
      production and plasmid stability. Major pathways and mechanisms of oxidative
      damage to proteins expressed in bacteria are reviewed. Damage to nucleic acids
      involved in gene expression also is considered. The methodologies for identifying
      oxidative damage to macromolecules are improving but are not yet adequate for on
      line feedback. This limits our ability to integrate information about these
      phenomena and the cellular responses into a quantitative model. Enough
      information is available, however, to consider changes in the time profile of
      dissolved oxygen as a cause for poor process performance.

PMID- 9622521
TI  - Intracellular UDP-N-acetylhexosamine pool affects N-glycan complexity: a
      mechanism of ammonium action on protein glycosylation.
AB  - Understanding the mechanisms by which ammonium ions affect glycosylation may
      suggest strategies for producing glycoproteins with homogeneous biological
      activity in the presence of undesirable byproducts of cellular energy metabolism.
      We have previously shown that ammonium ions cause an increase in the
      intracellular UDP-N-acetylhexosamine (UDPGNAc) pool, which may be responsible for
      the ammonium-induced increase in complexity and decrease in sialylation state of
      the N-linked oligosaccharide. To investigate this novel hypothesis, we induced an
      artificial increase in UDPGNAc pool by treating recombinant BHK cells expressing
      an IL-2 variant that features an artificial site for N-glycosylation, with
      glucosamine (1:2 molar ratio to glucose) and uridine (2 mmol L-1) in the absence
      of ammonium ions or glutamine. The product fractions collected during this
      treatment showed increased antennarity compared to product collected under
      control conditions. When this pool was returned to normal levels, the
      glycosylation pattern regained its original (control) features. However, the
      sialylation state remained unaffected, suggesting that the decreased sialylation
      observed under ammonium treatment is due to a different mechanism of action,
      possibly involving changes in intracellular pH. By pretreating the cells with 0.5
      mmol L-1 adenosine, and exposing them continuously to NH4Cl and adenosine we were
      able to prevent the ammonium-induced increase in UDPGNAc. Product fractions
      collected during this treatment showed unchanged antennarity but decreased
      sialylation of the N-linked oligosaccharide, thus conclusively demonstrating that
      ammonium ions act on protein glycosylation by at least two independent
      mechanisms, one of which involves an increase in the UDPGNAc pool.

PMID- 9622522
TI  - Increased phenylalanine production by growing and nongrowing Escherichia coli
      strain CWML2.
AB  - Chemostat selection at low dilution rate in glycerol-limited minimal medium was
      previously employed to isolate the mutant Escherichia coli strain CWML2 which
      exhibits shorter lag phases, decreased acetate production, and higher specific
      growth rates and biomass yields in batch culture (Weikert, C.; Sauer, U.; Bailey,
      J. E. Microbiology 1997, 143, 1567-1574). In this study, CWML2 was analyzed for
      its biochemical production capabilities in batch culture and under nongrowing
      conditions. Both CWML2 and MG1655 were transformed with plasmid pSY130-14, which
      encodes feedback resistant mutants of the enzymes chorismate mutase P-prephenate
      synthase and 3-hydroxy-d-arabinoheptulosonate-7-phosphate dehydratase, to enable
      phenylalanine production. In batch culture, transformed CWML2 produced twice as
      much phenylalanine as did MG1655:pSY130-14. In contrast to the reference strain,
      substantial growth-independent production of phenylalanine was calculated for
      CWML2:pSY130-14 by using Luedeking-Piret kinetic analysis. Over a period of 30 h,
      nongrowing cells of CWML2:pSY130-14 exhibited a 2.5-fold higher specific
      phenylalanine production rate. The apparent capability of E. coli CWML2 to partly
      uncouple metabolic activity from growth suggests a potentially general advantage
      of this class of modified hosts for production of biochemicals.

PMID- 9622523
TI  - Kinetics of ferrous iron oxidation by Leptospirillum bacteria in continuous
      cultures.
AB  - The oxidation of ferrous iron by Leptospirillum bacteria was studied in a
      continuous culture in the dilution rate range 0.009-0.077 h-1 and could be
      described with a rate equation for competitive ferric iron inhibition kinetics in
      terms of the ferric/ferrous iron ratio in the solution. The ferrous iron
      oxidation in the continuous culture was followed by means of oxygen and carbon
      dioxide concentration analyses in reference air and off-gas. From these
      measurements the oxygen consumption rate, rO2, the carbon dioxide consumption
      rate, rCO2, the biomass concentration, Cx, and the biomass specific oxygen
      consumption rate, qO2, in the culture were determined. The ferrous iron
      concentration in the culture was below accurate levels to determine with the
      usual titrimetric method and was therefore derived from measuring the solution
      redox potential. The degree of reduction balance was used to check the
      theoretically expected relation between the rates of ferrous iron, -rFe2+,
      oxygen, -rO2, and biomass, rx. The maximum biomass yield and maintenance
      coefficient on oxygen are Yoxmax = 0.047 mol of C/mol of O2 and mo = 0.057 mol of
      O2/(mol of C.h). The maximum specific oxygen consumption rate, qO2,max = 1.7 mol
      of O2/(mol of C.h), the affinity coefficient, Ks/Ki = 0.0005 mol of Fe2+/mol of
      Fe3+, and the maximum specific growth rate, micromax = 0.069 h-1, Ks/Ki = 0.0004,
      were fitted from the measured data. For several dilution rates, off-line
      respiratory measurements with cell suspension from the continuous culture were
      carried out in dynamic BOM-Eh measurements. The dissolved oxygen and redox
      potential were measured simultaneously and monitored. The measured value of
      qO2,max varied between 2.3 and 1.7 mol/(mol of C.h). The value of Ks/Ki = 0.0007
      was equal in all experiments. The measured values of qO2 in the continuous
      culture were well described with the kinetics determined in dynamic BOM-Eh
      measurements. It was concluded that dynamic BOM-Eh measurements are a convenient
      method to determine the kinetics of continuous culture grown Leptospirillum
      bacteria.

PMID- 9622524
TI  - Variation of stoichiometric ratios and their correlation for monitoring and
      control of animal cell cultures.
AB  - The stoichiometry of animal cell cultures is examined with respect to its
      variation and suitability for process monitoring and control. In addition to the
      two often used stoichiometric ratios, i.e., lactate yield from glucose (Lac/Glc)
      and ammonium yield from glutamine (NH4+/Gln), five other less well characterzied
      ones, i.e., ammonium yield from the total consumption of amino acids (NH4+/TAA),
      consumption of total amino acids to glutamine (TAA/Gln), essential amino acids to
      glutamine (EAA/Gln), glutamine to glucose (Gln/Glc), and oxygen to glucose
      (OUR/Glc), are also considered. A comparison of a number of cell lines including
      hybridoma, BHK, and CHO cells under a wide range of experimental conditions
      revealed that all the cell lines have similar patterns of variation of
      stoichiometry. In steady states of continuous culture, Lac/Glc and Gln/Glc are
      primarily determined by the residual glucose concentration while TAA/Gln and
      EAA/Gln correlate well with the residual glutamine concentration. Ammonium
      formation not only is a function of glutamine concentration but also is affected
      by the consumption of other amino acids, particularly at low residual glutamine
      concentrations. NH4+/TAA turned out to be a more suitable parameter to describe
      the ammonium formation. Large variations of all these stoichiometric ratios are
      found under conditions of relatively low residual concentrations of glucose and
      glutamine (both ca. < 0.2-0.5 mM). Above these concentrations the stoichiometric
      ratios are relatively constant and are independent of the cell lines. Thus, the
      correlations for these stoichiometric ratios may be directly used to control the
      nutrient concentration at low levels which are otherwise on-line difficult to
      determine. A stoichiometric equation is also derived for oxygen consumption. It
      is found that the metabolism of amino acids can significantly contribute to the
      consumption of oxygen. A correlation is obtained for OUR/Glc which may be used
      for the monitoring and control of mammalian cell cultures.

PMID- 9622525
TI  - Effect of elicitor dosage and exposure time on biosynthesis of indole alkaloids
      by Catharanthus roseus hairy root cultures.
AB  - Late exponential phase hairy root cultures of Catharanthus roseus were elicited
      with pectinase and jasmonic acid. The effects of elicitor concentration and
      exposure time on growth and levels of several compounds in the indole alkaloid
      biosynthetic pathway were monitored. Pectinase decreased the fresh weight to dry
      weight ratio of the roots, while addition of jasmonic acid had no significant
      effect. Selective effects on indole alkaloid yields were observed upon addition
      of elicitors. An increase of 150% in tabersonine specific yield was observed upon
      addition of 72 units of pectinase. Transient studies at the same level
      demonstrated possible catabolism as serpentine, tabersonine, and lochnericine
      levels decreased immediately after elicitation. The levels of these compounds
      recovered back to control levels or were higher than the control levels after
      some time. Jasmonic acid was found to be a unique elicitor leading to an
      enhancement in flux to several branches in the indole alkaloid pathway. Jasmonic
      acid addition caused an increase in the specific yields of ajmalicine (80%),
      serpentine (60%), lochnericine (150%), and horhammericine (500%) in dosage
      studies. Tabersonine, the likely precursor of lochnericine and horhammericine,
      decreased at lower levels of jasmonic acid and then increased with increasing
      jasmonic acid concentration. Transient studies showed that lochnericine and
      tabersonine levels go through a maxima, then decrease back to control levels and
      reduce below control levels, respectively. The yields of ajmalicine, serpentine,
      and horhammericine increased continuously after the addition of jasmonic acid.
      The methods described in this article could generally be used in devising
      strategies for enhancement in productivity of secondary metabolites and for
      probing and studying the complex secondary metabolite pathways in plant tissue
      cultures.

PMID- 9622526
TI  - Selective synchronization of Tetrahymena pyriformis cell populations and cell
      growth kinetics during the cell cycle.
AB  - A selection synchronization technique based on ingestion of tantalum particles
      has been applied to obtain synchronized cultures of the filter feeding ciliate
      Tetrahymena pyriformis. Cell concentrations and cell volume distributions of
      synchronized cell populations have been monitored for more than four average
      generation times. A simple curve-fitting method has been used to decompose the
      cell volume distributions of a synchronous population into two populations
      representing cells before and after cell division. In this way, the time course
      of the growth of an initially synchronous culture is decomposed into the growth
      of successive generations. The data indicate that at any given time only two
      generations of cells are present in significant numbers. The measured cell volume
      distributions show that T. pyriformis has a complicated growth pattern during the
      cell cycle. Newborn T. pyriformis cells do not grow significantly at the
      beginning of the cell cycle. After the nongrowing stage, cells start growing in a
      possibly exponential rate before cells enter into a second nongrowing stage. The
      second nongrowing stage lasts until cell division. The presented data demonstrate
      that growing cell populations can be viewed as the composite of cells belonging
      to different generations. This concept has important implications for solving
      corpuscular models of cell growth.

PMID- 9622527
TI  - Extractive fermentation for enhanced propionic acid production from lactose by
      Propionibacterium acidipropionici.
AB  - An extractive fermentation process using an amine extractant and a hollow-fiber
      membrane extractor to selectively remove propionic acid from the fermentation
      broth was developed to produce propionate from lactose. Compared to the
      conventional batch fermentation, the extractive fermentation had a much higher
      productivity ( approximately 1 g/(L.h) or 5-fold increase), higher propionate
      yield (up to 0.66 g/g or more than 20% increase), higher final product
      concentration (75 g/L or higher), and higher product purity ( approximately 90%).
      Meanwhile, acetate and succinate productions in the extractive fermentation were
      significantly reduced. The improved fermentation performance can be attributed to
      the reduced product inhibition and a possible metabolic pathway shift to favor
      more propionic but less acetic and succinic acid production. The process was
      stable and gave consistent long-term performance over the 1. 5-month period
      studied. The effects of propionate concentration, pH, and amine content in the
      solvent on the extractive fermentation were also studied and are discussed in
      this paper.

PMID- 9622528
TI  - Characterization of hematopoietic cell expansion, oxygen uptake, and glycolysis
      in a controlled, stirred-tank bioreactor system.
AB  - Cultures of umbilical cord blood and mobilized peripheral blood mononuclear cells
      were carried out in a stirred bioreactor with pH and dissolved oxygen control.
      Expansion of total cells and colony-forming units granulocyte-macrophage was
      greatly enhanced by the use of a cell-dilution feeding protocol (as compared to a
      cell-retention feeding protocol). The specific oxygen consumption rate (qO2) for
      these cultures ranged from 1.7 x 10(-8) to 1.2 x 10(-7) micromol/(cell.h). The
      maximum in qO2 for each culture closely corresponded with the maximum percentage
      of progenitor or colony-forming cells (CFCs) present in the culture. The maximum
      qO2 values are slightly less than those reported for hybridomas, while the lowest
      qO2 values are somewhat greater than those reported for mature granulocytes.
      Examination of the ratio of lactate production to oxygen consumption in these
      cultures suggests that post-progenitor cells of the granulomonocytic lineage
      obtain a greater portion of their energy from glycolysis than do CFCs. The
      different metabolic profiles of CFCs and more mature cells suggest that
      monitoring the uptake or production of oxygen, lactate, and other metabolites
      will allow estimation of the content of several cell types in culture.

PMID- 9622529
TI  - Immobilization of alpha-amylase to a composite temperature-sensitive membrane for
      starch hydrolysis.
AB  - A composite membrane was made by casting hydrogel onto a nonwoven polyester
      support and used for enzyme immobilization. The hydrogel consists of N
      isopropylacrylamide, cross-linker N, N'-methylenebis(acrylamide), 2-hydroxyethyl
      methacrylate, soluble starch, and N-(acryloxy)succinimide (NAS). The composite
      membrane is temperature-sensitive with a lower critical solution temperature
      (LCST) around 35 degreesC. It responds to temperature change by swelling below
      the LCST and shrinking above the LCST, corresponding to opening and closing of
      the membrane pores. alpha-Amylase was immobilized to the membrane by covalent
      bonds through reacting with the high reactive ester groups in NAS. The membrane
      immobilized enzyme retained 32% of specific activity toward soluble starch when
      compared with that of free enzyme, and its properties were characterized and
      compared with those of the free enzyme. The immobilized enzyme was more thermally
      stable than the free enzyme. Kinetic constants, (Km) and the activation energy of
      the immobilized enzyme were both larger than those of the free enzyme. Starch
      hydrolysis with the immobilized enzyme was investigated in two-compartment
      permeation cells with a composite membrane between the cells. Reaction was
      carried out by hydrolyzing soluble starch in the donor side and collecting the
      hydrolyzed products in the receptor side. This reactor could be operated with
      temperature cycling to enhance the reaction and facilitate separation of products
      from the substrate. The best operating condition is cycling the temperature
      between 50 and 20 degrees C every 5 min. The membrane reactor was operated up to
      eight times for successive starch hydrolysis.

PMID- 9622530
TI  - Application of membrane tubing aeration and perfluorocarbon To improve oxygen
      delivery to hairy root cultures 
AB  - Growth and atropine production by Atropa belladonna hairy roots were studied in
      bioreactor cultures using porous polypropylene membrane tubing as a supplementary
      aeration device and with FC-43 perfluorocarbon emulsion added to the medium. Both
      these treatments were applied to improve oxygen transfer to the roots. Membrane
      tubing aeration allowed direct delivery of oxygen within the root clump, thus
      overcoming mass transfer resistances associated with poor intraclump penetration
      of liquid convective currents. Combined air sparging and membrane tubing aeration
      in a gas-driven bioreactor supported biomass levels 32-65% higher than sparging
      only of air or oxygen-enriched air at the same total gas flow rate. The optimal
      air flow rate ratio between the sparger and membrane tubing giving the maximum
      final biomass concentration was 0.2:0.4 L min-1. Intraclump dissolved oxygen
      tensions at high biomass densities were generally greater using air delivered by
      combined sparger-membrane tubing aeration than with sparging only of air or
      oxygen-enriched air. Specific atropine levels were not significantly affected by
      membrane tubing aeration. Indicators of anaerobic metabolism, such as lactic
      acid, ethanol, and ADH activity levels, were not significantly different in
      sparged and membrane-aerated systems; A. belladonna hairy roots also did not
      produce aerenchyma in response to oxygen limitations. Addition of perfluorocarbon
      emulsion to Murashige and Skoog medium in sparged stirred tank bioreactors did
      not improve growth, even when the emulsion was continuously recycled for re
      aeration in an external vessel. Perfluorocarbons are associated with enhancement
      of gas-liquid oxygen transfer, so their ineffectiveness in this work most likely
      reflects the dominance of liquid-solid transfer resistances in hairy root
      cultures. The results of this investigation highlight the importance of
      developing new approaches for site-directed aeration of hairy root cultures,
      targeting oxygen delivery into the zones of highest root density.

PMID- 9622531
TI  - Turnover capacity of coprinus cinereus peroxidase for phenol and monosubstituted
      phenols 
AB  - Coprinus cinereus peroxidase (CIP) and other peroxidases are susceptible to
      mechanism-based inactivation during the oxidation of phenolic substrates. The
      turnover capacity (defined as the molar or mass concentration of substrate
      oxidized per unit concentration of enzyme inactivated) of CIP was quantified for
      phenol and 11 monosubstituted phenols under conditions in which enzyme
      inactivation by mechanisms involving hydrogen peroxide alone were minimized.
      Turnover capacities varied by nearly 2 orders of magnitude (absolute values on
      the order of 10(5)-10(6) on a molar basis), depending on the substituent. On a
      mass basis, the enzyme consumption corresponding to the lowest turnover
      capacities is considerable and may influence the economic feasibility of proposed
      industrial applications of peroxidases. Within a range of substituent
      electronegativity values, molar turnover capacities correlated well (r2 = 0.89)
      with substituent effects quantified by radical sigma values and
      semiquantitatively with homolytic O-H bond dissociation energies of the phenolic
      substrates, suggesting that phenoxyl radical intermediates are probably involved
      in the suicide inactivation of CIP. The correlation range in each case did not
      include phenols with highly electron-withdrawing (nitro and cyano) substituents
      because they are not oxidized by CIP, nor phenols with highly electron-donating
      (hydroxy and amino) substituents because they led to virtually complete
      inactivation of the enzyme with minimal substrate removal. In the latter case we
      conclude that inactivation of CIP during the oxidation of hydroxy- and amino
      substituted phenols occurs by a different mechanism than that of the other
      phenolic substrates.

PMID- 9622532
TI  - Dye affinity adsorbent replacement optimization.
AB  - A method to determine the optimal replacement time for dye affinity adsorbents
      used in protein purification processes that are subjected to severe regeneration
      conditions has been developed. To demonstrate the utility of the method, an
      experimental fixed-bed decay model was employed to determine the optimum number
      of cycles for the adsorbent replacement. This number is a function of the column
      regeneration frequency and of the capital and operation costs. The implications
      of the results on the design and operation of dye-ligand chromatographic
      processes are discussed.

PMID- 9622533
TI  - Artificial antibodies for affinity chromatography of homologous proteins:
      application to blood clotting proteins.
AB  - A method to readily isolate antibodies that bind to only one member of a family
      of homologous proteins is described. A library of different single chain antibody
      fragments can be displayed on the surface of a bacteriophage vector. Individual
      antibodies from this library recognizing a particular protein from a family of
      homologous proteins can be readily isolated by a two-step affinity screening
      process. In the first step antibodies which bind specifically to the undesired
      proteins or to homologous regions of the proteins are removed. In the second
      step, those antibodies specifically recognizing the desired protein are then
      isolated. Using this procedure and starting with a naive antibody library, a
      single chain antibody fragment specific to the blood clotting protein, Protein C,
      which did not recognize either of the homologous proteins, Factor IX or Factor X,
      was isolated. Similarly an antibody specific to Factor IX, but not Factor X or
      Protein C, was also isolated. The isolated antibodies can be readily produced,
      purified, and affixed to sepharose beads for affinity chromatography of the blood
      clotting factors. One of the key advantages to this procedure over conventional
      monoclonal antibody isolation is that the antibodies are isolated and produced in
      vitro so a broad range of related proteins, toxins, viruses, or other products
      can be targeted.

PMID- 9622534
TI  - Technique for the kinetic characterization of the metabolic reactions of
      hepatocytes in adhesion culture.
AB  - In this paper, we report on the development of a technique for the kinetic
      characterization of the metabolic reactions of liver cells in adhesion culture.
      The technique is based on the use of a continuous-flow bioreactor which is
      designed and operated in such a way as to ensure a uniform distribution of
      metabolite at the cell site: hence, the metabolite concentration at the surface
      of cells cultured in adhesion at the bottom of the bioreactor equals that in the
      stream leaving the bioreactor. Under steady conditions, the rate of a given cell
      reaction is directly estimated from the metabolite concentration difference in
      the streams entering and leaving the bioreactor and can be correctly related to
      the actual concentration at the cell surface. Such a technique was used for a
      preliminary investigation of the kinetics of ammonia elimination, urea synthesis,
      and phenolsulfonphthalein (PSP) elimination by primary rat hepatocytes cultured
      in adhesion on collagen, with respect to ammonia and PSP concentration,
      respectively. The rate at which the hepatocytes eliminated ammonia increased with
      increasing ammonia concentrations according to a Michaelis-Menten kinetics. The
      hepatocytes synthesized urea also in the absence of ammonia in the medium: as
      ammonia concentration increased, the cells synthesized urea at a rate that
      increased according to a saturation kinetics. In the concentration range
      investigated, the hepatocytes eliminated PSP at a rate that increased linearly
      with the actual PSP concentration in the medium. Such kinetic information can be
      coupled to the mechanism of metabolite transport in a hybrid liver support device
      to yield an effective device design for the treatment of acute liver failure.

PMID- 9622535
TI  - Conjugation of trypsin by temperature-sensitive polymers containing a
      carbohydrate moiety: thermal modulation of enzyme activity.
AB  - Novel temperature-sensitive polymers containing glucose units in their backbone
      were synthesized and covalently conjugated to trypsin. A series of copolymers
      based on N-isopropylacrylamide (NIPAAm) and glucosyoxylethyl methacrylate (GEMA)
      were prepared by using 4,4'-azobis(4-cyanovaleric acid) as an initiator, which
      resulted in one terminal carboxylic acid group per polymer chain. The polymers
      were conjugated to primary amine groups of trypsin with water-soluble
      carbodiimide as a coupling agent, which led to a star-shaped conformation. The
      polymer-enzyme conjugation was confirmed and characterized by size exclusion and
      reversed-phase chromatography. Almost of all amine groups in trypsin available
      for the conjugation were consumed and, consequently, a very dense layer of
      copolymers was actually coated around the enzyme surface. The conjugated enzymes
      exhibited reversible precipitation/resolubilization behaviors over a wide range
      of temperatures, depending on the content of GEMA in the copolymer. They also
      demonstrated no detectable self-digestion (autolysis) process, but the
      unconjugated enzyme showed very severe autolysis that led to a rapid inactivation
      in aqueous solution. When bovine serum albumin was used as a substrate, the
      protein substrate was not attacked by the conjugated enzyme, but completely
      digested by the unconjugated enzyme. This result was presumably caused by a
      steric repulsion process of the attached polymer chains around the enzyme toward
      the protein substrate. However, the enzyme retained sufficient activity against a
      low molecular weight substrate. Interestingly, the conjugated enzymes
      demonstrated very peculiar enzyme activity-temperature profiles, with two
      apparent optimal temperatures, indicating that a temperature-controlled collapse
      and flocculation of the copolymers around the enzyme surface modulated the mass
      transfer rates of substrate to the active site of the enzyme. The conjugated
      enzymes also exhibited improved thermal stability with increasing the amount of
      carbohydrate units in the polymer chain.

PMID- 9622536
TI  - Characterization of the degradation of polylactic acid polymer in a solid
      substrate environment.
AB  - Polylactic acid (PLA) polymer film was degraded in abiotic and biotic
      environments to understand the role of microbes in the degradation process of
      lactic acid based polymers. The degradation studies were conducted in a well
      characterized biotic system, an abiotic system, a sterile aqueous system, and a
      desiccated environment maintained at 40, 50, and 60 degrees C. The combination of
      experiments in different environments isolated the distinct effect of microbes,
      water, and temperature on the morphological changes in the polymer during
      degradation. Due to lack of availability of radiolabeled PLA, various analytical
      techniques were applied to observe changes in the rate and/or mechanism of
      degradation. CO2 evolved, weight loss, and molecular weights were measured to
      evaluate the extent of degradation. X-ray diffraction and differential scanning
      calorimetry techniques monitored the morphological changes in the polymer. FTIR
      was used as a semiquantitative tool to gather information about the chemistry of
      the degradative process. Neither of the above analytical techniques indicated any
      difference in the rate or mechanism of degradation attributable to the presence
      of microorganisms. The extent of degradation increased at higher process
      temperatures. FTIR data were evaluated for significant statistical difference by
      t-test hypothesis. The results confirmed hydrolysis of ester linkage as the
      primary mechanism of degradation of PLA. On the basis of these data, a probable
      path of PLA degradation has been suggested.

PMID- 9622538
TI  - Biodegradability behavior of cross-linked calcium caseinate films 
AB  - gamma-Irradiation was used to produce free-standing biodegradable caseinate
      films. The effect of the irradiation dose (i.e., the number of cross-links) on
      the biodegradability behavior of these films using a strain of Pseudomonas
      aeruginosa was investigated. Results showed that the overall degradation
      processes were similar for both types of films (4 or 64 kGy). The main difference
      was observed in terms of the period of degradation which was delayed 8 days for
      the film containing the highest extent of cross-linking (64 kGy).

PMID- 9622537
TI  - Adaptive calibration scheme for quantification of nutrients and byproducts in
      insect cell bioreactors by near-infrared spectroscopy.
AB  - Spectroscopic methods are gaining in popularity in biotechnology because of their
      ability to deliver rapid, noninvasive measurements of the concentrations of
      multiple chemical species. Such measurements are particularly necessary for the
      implementation of control schemes for cell culture bioreactors. One of the major
      challenges to the development of spectroscopic methods for bioreactor monitoring
      is the generation of accurate and robust calibration models, particularly because
      of the inherent variability of biological processes. We have evaluated several
      methods of building calibration models, including synthetic calibrations and
      medium spiking methods. The approach that consistently produced reliable models
      incorporated samples removed from a bioreactor that were subsequently altered so
      as to increase the sample variation. Several large volume samples were removed
      from a bioreactor at varying time points and divided into multiple aliquots to
      which were added random, known amounts of the analytes of interest. Near-infrared
      spectra of these samples were collected and used to build calibration models.
      Such models were used to quantify analyte concentrations from independent samples
      removed from a second bioreactor. Prediction errors for alanine, glucose,
      glutamine, and leucine were 1.4, 1.0, 1.1, and 0.31 mM, respectively. This
      adaptive calibration method produces models with less error and less bias than
      observed with other calibration methods. Somewhat more accurate measurements
      could be attained with calibrations consisting of a combination of synthetic
      samples and spiked medium samples, but with an increase in calibration
      development time.

PMID- 9622539
TI  - Combined influence of growth and drying conditions on the activity of dried
      lactobacillus plantarum 
AB  - The production of active dried starter cultures can be influenced at several
      levels in the production process. In this paper the following process factors are
      discussed: osmotic stress during growth and cell density prior to drying.
      Contradicting results are reported in the literature on the influence of osmotic
      stress during growth on the residual activity after drying. The combined approach
      in which two process factors were studied at a time resulted in an explanation
      for the discrepancy in earlier work. The cell density prior to drying had an
      important influence on the glucose fermenting activity after drying. Residual
      activities ranging from 0.10 to 0.83 were achieved using initial cell densities
      between 0.025 and 0.23 g of cell/g of sample, respectively. The drying tolerance
      of cells grown with osmotic stress of 1 M NaCl was low (residual activity = 0.
      06) and was not related to the cell density prior to drying. The influence of
      osmotic stress during growth on the drying tolerance of Lactobacillus plantarum
      was dependent on the cell density prior to drying.

PMID- 9622540
TI  - Increase of primary HIV-1 production in human peripheral blood mononuclear cells
      by intermittent medium replenishment.
AB  - Mitogen-stimulated human peripheral blood mononuclear cells (H-PBMCs) are
      conventionally used to culture primary human immunodeficiency virus type-1 (HIV
      1) isolates in vitro. In this study, we attempt to increase the quality of
      primary HIV-1 stocks harvested from H-PBMC culture using medium replenishment
      procedures. Experimental/analysis results indicate that more frequent medium
      replenishment may not lead to improved quantity and quality of harvested virus
      stock titers, as determined by the viral core (p24) antigen content, viral
      infectivity, and viral particle-to-infectious unit ratio. This finding implies
      the conditioning factor(s) present in H-PBMC culture may be important for primary
      HIV-1 production. The optimal rate for intermittent medium replenishment to
      achieve the lowest viral particle-to-infectious unit ratio is around 0.25
      volume/volume/day.

PMID- 9622541
TI  - Orally active benzamide antipsychotic agents with affinity for dopamine D2,
      serotonin 5-HT1A, and adrenergic alpha1 receptors.
AB  - New antipsychotic drugs are needed because current therapy is ineffective for
      many schizophrenics and because treatment is often accompanied by extrapyramidal
      symptoms and dyskinesias. This paper describes the design, synthesis, and
      evaluation of a series of related (aminomethyl)benzamides in assays predictive of
      antipsychotic activity in humans. These compounds had notable affinity for
      dopamine D2, serotonin 5-HT1A, and alpha1-adrenergic receptors. The
      arylpiperazine 1-[3-[[4-[2-(1-methylethoxy)phenyl]-1-piperazinyl]methyl]benzoyl]p
      ipe ridine (mazapertine, 6) was chosen because of its overall profile for
      evaluation in human clinical trials. The corresponding 4-arylpiperidine
      derivative 67 was also highly active indicating that the aniline nitrogen of 6 is
      not required for activity. Other particularly active structures include
      homopiperidine amide 14 and N-methylcyclohexylamide 31.

PMID- 9622542
TI  - Novel benzothiazolin-2-one and benzoxazin-3-one arylpiperazine derivatives with
      mixed 5HT1A/D2 affinity as potential atypical antipsychotics.
AB  - Since it was known that 5HT properties (5HT1A agonism or 5HT2A antagonism)
      combined with D2 antagonism may lead to atypical antipsychotic drugs, a series of
      19 benzothiazolin-2-one and benzoxazin-3-one derivatives possessing the
      arylpiperazine moiety was prepared, and their binding profiles were investigated.
      All tested compounds displayed very high affinities for the 5HT1A and D2
      receptors. Therefore, further pharmacological studies were carried out on
      selected compounds (24, 27, 30, 46, and 47). This evaluation in rats clearly
      revealed potent antipsychotic properties along with a decrease of extrapyramidal
      side effects. These derivatives are currently under preclinical development.

PMID- 9622543
TI  - Cyclic HIV protease inhibitors: design and synthesis of orally bioavailable,
      pyrazole P2/P2' cyclic ureas with improved potency.
AB  - Highly potent HIV-1 protease (HIVPR) inhibitors have been designed and
      synthesized by introducing bidentate hydrogen-bonding oxime and pyrazole groups
      at the meta-position of the phenyl ring on the P2/P2' substituents of cyclic
      ureas. Nonsymmetrical cyclic ureas incorporating 3(1H)-pyrazolylbenzyl as P2 and
      hydrophilic functionalities as P2' show potent protease inhibition and antiviral
      activities against HIV and have good oral bioavailabilities. The X-ray structure
      of HIVPR.10A complex confirms that the two pyrazole rings of 10A form bidentate
      hydrogen bonds with the side-chain oxygen (C=O) and backbone nitrogen (N-H) of
      Asp30/30' of HIVPR.

PMID- 9622544
TI  - Arylpiperazines with serotonin-3 antagonist activity: a comparative molecular
      field analysis.
AB  - Comparative molecular field analysis (CoMFA) is applied to antagonists of the 5
      HT3 receptor. Analysis is done separately on three published sets of
      arylpiperazines and on a combination of the three sets. d-Tubocurarine, a
      conformationally restricted 5-HT3 ligand, is used as a template to assist in
      selecting the conformation of the antagonists for CoMFA alignment. Two forms of
      the arylpiperazines (neutral and protonated) and three different kinds of
      calculated charges (Gasteiger-Huckel, AM1, and AM1 with solvation effect
      included) are compared. Protonated structures give better statistical results
      than the neutral species. The way in which charges are calculated does not
      greatly affect the results. In terms of molecular fields, the behavior in each
      separate set of compounds cannot be extrapolated to the combined set of 47
      compounds. The average value of r2cv from PLS cross-validation on the combined
      set is 0.70 and varies between 0.56 and 0.80 depending on the orientation of the
      molecules in the coordinate system. The CoMFA model is tested on four compounds
      not in the training set: quipazine, N-methylquipazine, 4-phenyl-N
      methylquipazine, and KB-6933. Mean agreement of experimental and predicted pKi
      values of the antagonists is 0.7 log unit. Novel structural modifications are
      interpreted by the CoMFA model.

PMID- 9622545
TI  - Newly synthesized L-enantiomers of 3'-fluoro-modified beta-2'-deoxyribonucleoside
      5'-triphosphates inhibit hepatitis B DNA polymerases but not the five cellular
      DNA polymerases alpha, beta, gamma, delta, and epsilon nor HIV-1 reverse
      transcriptase.
AB  - Novel beta-L-2',3'-dideoxy-3'-fluoro nucleosides were synthesized and further
      converted to their 5'-triphosphates. Their inhibitory activities against
      hepatitis B virus (HBV) and duck hepatitis B virus (DHBV) DNA polymerases, human
      immunodeficiency virus (HIV) reverse transcriptase (RT), and the cellular DNA
      polymerases alpha, beta, gamma, delta, and epsilon were investigated and compared
      with those of the corresponding 3'-fluoro-modified beta-d-analogues. The 5'
      triphosphates of 3'-deoxy-3'-fluoro-beta-L-thymidine (beta-L-FTTP), 2',3'-dideoxy
      3'-fluoro-beta-L-cytidine (beta-L-FdCTP), and 2',3'-dideoxy-3'-fluoro-beta-l-5
      methylcytidine (beta-L-FMetdCTP) emerged as effective inhibitors of HBV/DHBV DNA
      polymerases (IC50 = 0.25-10.4 microM). They were either equally (FTTP) or less
      (FMetdCTP, FdCTP) effective than their beta-d-counterparts. Also the 5'
      triphosphate of beta-L-thymidine (beta-L-TTP) was shown to be a strong inhibitor
      of these two viral enzymes (IC50 = 0.46/1.0 microM). However, all beta-L-FdNTPs
      (also beta-L-TTP) were inactive against HIV-RT, a result which contrasts sharply
      with the high efficiency of the beta-D- FdNTPs against this polymerase. Between
      the cellular DNA polymerases only the beta and gamma enzymes displayed a critical
      susceptibility to beta-D-FdNTPs which is largely abolished by the beta-L
      enantiomers. These results recommend beta-L-FTdR, beta-L-FCdR, and beta-L-FMetCdR
      for further evaluation as selective inhibitors of HBV replication at the cellular
      level.

PMID- 9622546
TI  - 6beta-Acetoxynortropane: a potent muscarinic agonist with apparent selectivity
      toward M2-receptors.
AB  - A series of tropane derivatives, related in structure to baogongteng A (1), an
      alkaloid from a Chinese herb, were synthesized. 6beta-Acetoxynortropane (5) had
      weak affinity (Ki 22 microM) for central (M1) muscarinic receptors in a
      [3H]quinuclidinyl benzilate binding assay but had extremely high affinity (Ki 2.6
      nM) and selectivity for M2-muscarinic receptors expressed in CHO cells. It had 13
      fold lower affinity for M4-receptors, 260-fold lower affinity for M3-receptors,
      and 8200-fold lower affinity for M1-receptors expressed in CHO cells. The 6beta
      carbomethoxy analogue (14) of baogongteng A had only weak affinity for M2
      muscarinic receptors, as did 6beta-carbomethoxynortropane (13) and 6beta
      acetoxytropane (4). In transfected CHO cells, 6beta-acetoxynortropane (5) was an
      agonist at M2-receptors, based on a GTP-elicited decrease in affinity, and a full
      agonist with an IC50 of 11 nM at M4-receptors, based on inhibition of cyclic AMP
      accumulation, while being a full agonist at M1-receptors with an EC50 of 23 nM
      and a partial agonist at M3-receptors with an EC50 of 3.6 nM, based in both cases
      on stimulation of phosphoinositide breakdown. All of the 16 tropane derivatives
      had weak affinities for central alpha4beta2-nicotinic receptors with 6beta
      carbomethoxynortropane (13) having the highest affinity, which was still 150-fold
      less than that of nicotine. 6beta-Acetoxynortropane (5) represents a potent
      muscarinic agonist with apparent selectivity toward M2-receptors.

PMID- 9622547
TI  - Structure-activity relationships of the 7-substituents of 5,4'-diamino-6,8,3'
      trifluoroflavone, a potent antitumor agent.
AB  - Recently, we reported that 5,4'-diamino-6,8,3'-trifluoroflavone (1b) exhibits
      potent antitumor activity against certain types of human cancer cell lines both
      in vitro and in vivo. Since the antiproliferative activity of 5,4'-diaminoflavone
      (1a), the lead compound of 1b, was modulated by the addition of apigenin, we
      hypothesized that the 7-position is important for the interaction with a putative
      target molecule. On the basis of this hypothesis, the structure-activity
      relationships of the substituents at the 7-position of 1b were explored. As a
      result, 7-methyl (7a), 7-hydroxymethyl (7l), 7-(acyloxy)methyl (9a,c,e,g,j), and
      7-aminomethyl (12f) derivatives were found to exhibit comparable or superior
      antitumor activity to compound 1b against MCF-7 cells both in vitro and in vivo
      (po administration). In particular, compounds 9e,g,j, and 12f were sufficiently
      water-soluble as compared with 1b which hardly solubilizes in water. A lipophilic
      7-(hexanoyloxy)methyl derivative (9c) was also found to exhibit strong antitumor
      activity especially in vivo. Since the modes of action and the target molecule(s)
      are unknown, a mechanistic study will be important in the future.

PMID- 9622548
TI  - Structural analysis of thrombin complexed with potent inhibitors incorporating a
      phenyl group as a peptide mimetic and aminopyridines as guanidine substitutes.
AB  - The structure of the noncovalent complex of human alpha-thrombin with a
      nonpeptide inhibitor containing a central phenyl scaffold, N-[2-[5-methyl-3-(2
      chlorophenylsulfonyloxy)phenoxy]ethyl]-N- methyl-4 -aminopyridine (1), has been
      determined to 2.20 A resolution. In addition, the thrombin-bound structures of
      two distinct amino acid-based inhibitors (3 and 4) containing different
      aminopyridine-derived guanidine mimetics have been determined. Each compound
      occupies the same region of the active site and projects an aminopyridine, a
      central hydrophobic group, and an aryl group, into the S1, S2, and aryl subsites
      on thrombin. Nonpeptide 1 forms only one direct intermolecular hydrogen bond to
      the thrombin active site and forms no hydrogen bonds to ordered molecules of
      solvent. Close contacts are observed between main-chain carbonyl groups on
      thrombin and the edges of the central phenyl and aminopyridine rings and the
      sulfonyl group of 1 such that atoms carrying opposite partial charges are
      juxtaposed. Aminopyridine groups in 3 and 4 also form close contacts with the
      edges of carbonyl groups on thrombin and are flexibly accommodated in the S1
      subsite. Superposition of the bound conformations of 1 and D-Phe-Pro
      amidobutylguanidine (2) revealed that the central phenyl scaffold of 1
      substitutes for the peptide main chain of 2.

PMID- 9622549
TI  - New alkenyldiarylmethanes with enhanced potencies as anti-HIV agents which act as
      non-nucleoside reverse transcriptase inhibitors.
AB  - Twenty-two new alkenyldiarylmethanes (ADAMs) were synthesized and evaluated for
      inhibition of HIV-1 replication. The most potent compound proved to be methyl
      3',3"-dichloro-4',4"-dimethoxy-5', 5"-bis(methoxycarbonyl)-6,6-diphenyl-5
      hexenoate (ADAM II), which displayed an EC50 of 13 nM for inhibition of the
      cytopathic effect of HIV-1RF in CEM-SS cells. ADAM II inhibited HIV-1 reverse
      transcriptase with an IC50 of 0.3 microM but was inactive as an inhibitor of HIV
      1 attachment/fusion to cells, protease, integrase, and the nucleocapsid protein.
      Molecular target-based and cell-based assays revealed that ADAM II acted
      biologically as a nonnucleoside reverse transcriptase inhibitor (NNRTI). ADAM II
      inhibited replication of a wide variety of laboratory, clinical, and clade
      representative isolates of HIV-1 in T cell lines and cultures of peripheral blood
      mononuclear cells or monocyte/macrophages. Mutations that conferred resistance to
      ADAM II clustered at residues 101, 103, 108, 139, 179, 181, and 188, which line
      the nonnucleoside binding pocket of HIV-1 reverse transcriptase. However, HIV-1
      NL4-3 strain expressing a mutation at residue 100 of reverse transcriptase, and
      an AZT-resistant virus, displayed increased sensitivity to ADAM II. Thus, ADAM II
      could serve as an adjunct therapy to AZT and NNRTIs that select for L100I
      resistance mutations.

PMID- 9622550
TI  - Vancomycin: conformational consequences of the sugar substituent.
AB  - High-resolution, three-dimensional structures of vancomycin and aglyco-vancomycin
      in DMSO were determined by nuclear magnetic resonance, metric matrix distance
      geometry, and molecular dynamics calculations. Conformational flexibility fast on
      the NMR time scale was examined by ensemble-based calculations which apply the
      experimentally derived restraints as an ensemble average. Two families of
      conformations of vancomycin, differing in the positioning of the vancosamine
      substituent, were observed. In contrast, the aglyco-vancomycin adopts only one
      conformation in solution. The conformations of vancomycin and the aglyco
      vancomycin differ in the alignment of the amide protons which participate in the
      hydrogen-bonding network with the cell-wall precursor and orientation of the
      aromatic rings relative to the backbone. Therefore, the high-resolution
      structural characterization provides insight into a possible role of
      glycosylation on the activity of this important family of antibiotics.

PMID- 9622551
TI  - Specific and irreversible cyclopeptide inhibitors of dipeptidyl peptidase IV
      activity of the T-cell activation antigen CD26.
AB  - The dipeptidyl peptidase IV (DPP IV) activity of CD26 is characterized by its
      post-proline-cleaving capacity that plays an important but not yet understood
      role in biological processes. Here we describe a new family of specific and
      irreversible inhibitors of this enzyme. Taking into account the substrate
      specificity of DPP IV for P2-P1><-P1' cleavage, we have designed and synthesized
      cyclopeptides c[(alphaH2N+)-Lys-Pro-Aba-(6-CH2-S+R2)-Glyn] 2TFA- (Aba = 3
      aminobenzoic acid, R = alkyl) possessing a proline at the P1 position and a
      lysine in the P2 position, which allows the closing of the cycle on its side
      chain. These molecules show a free N-terminus, necessary for binding to the CD26
      catalytic site, and a latent quinoniminium methide electrophile, responsible for
      inactivation. Treatment of c[alphaZ-Lys-Pro-Aba-(6-CH2-OC6H5)-Glyn], obtained by
      peptide synthesis in solution, with R2S/TFA simutaneously cleaved the Z
      protecting group and the phenyl ether function and led to a series of
      cyclopeptide sulfonium salts. These cyclopeptides inhibited rapidly and
      irreversibly the DPP IV activity of CD26, with IC50 values in the nanomolar
      range. Further studies were carried out to investigate the effect of the
      modification of the ring size (n = 2 or 4) and the nature of the sulfur
      substituents (R = Me, Bu, Oct). Cycle enlargement improved the inhibitory
      activity of the methylsulfonio cyclopeptide, whereas the increase of the alkyl
      chain length on the sulfur atom had no apparent effect. Other aminopeptidases
      were not inhibited, and a much weaker activity was observed on a novel isoform of
      DPP IV referred to as DPP IV-beta. Thus, this new family of irreversible
      inhibitors of DPP IV is highly specific to the peptidase activity of CD26.

PMID- 9622552
TI  - [125I/127I/131I]Iodorhodamine: synthesis, cellular localization, and
      biodistribution in athymic mice bearing human tumor xenografts and comparison
      with [99mTc]hexakis(2-methoxyisobutylisonitrile).
AB  - The synthesis of halogenated rhodamine (Rh) derivatives was carried out by
      controlling the stoichiometry of the halogenating agents, bromine and iodine
      monochloride. In the no-carrier-added synthesis of radioiodinated rhodamine 123,
      direct labeling of rhodamine 123 (Rh 123) with Na125I/Na131I required the
      presence of the oxidant peracetic acid. 125I/131I-Rh 123 was synthesized in
      modest yields (40-45%). HPLC purification separated Rh 123 from its mono- and
      diiodo derivatives. Monohalogenation of Rh 123 did not alter the compound's
      ability to permeate viable cells and localize in mitochondria. 125I/131I-Rh 123
      was stable in serum in vitro but rapidly metabolized after intravenous injection
      into mice. Consequently, scintigraphy and biodistribution data reveal poor
      targeting of subcutaneously growing human tumor xenografts. The results are
      compared to those obtained following the administration of [99mTc]hexakis(2
      methoxyisobutylisonitrile) which also did not image human tumor xenografts in
      nude mice.

PMID- 9622553
TI  - Selective inhibitors of monoamine oxidase (MAO). 5. 1-Substituted phenoxathiin
      inhibitors containing no nitrogen that inhibit MAO A by binding it to a
      hydrophobic site.
AB  - It is believed that a monoamine oxidase (MAO) inhibitor specific for MAO A, which
      is reversibly bound to this enzyme and displaceable by tyramine, will be an
      antidepressant which will not cause a rise in blood pressure when tyramine
      containing foods are ingested. Some linear tricyclic compounds with a larger and
      a smaller group forming the central ring and with a lipophilic group ortho to the
      larger group (here mostly the SO2 function of phenoxathiin 10,10-dioxide) are
      reported to have the sought properties. Potency appears to require short length
      and relatively small cross section for the substituent. The 1-ethyl (13), 1-vinyl
      (22), 1-trifluoromethyl (27), and 1-iodo (76) phenoxathiin dioxides had the best
      profiles. Structure-activity relationships, syntheses, and a possible rationale
      for the selectivity of these compounds and related tricyclics are given. Compound
      13 was selected for further development. A summary of pharmacological data for 13
      is given.

PMID- 9622554
TI  - Design, synthesis, and biological evaluation of a second generation of
      pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines as potent and selective A2A
      adenosine receptor antagonists.
AB  - New A2A adenosine receptor antagonists in the series of pyrazolo[4, 3-e]-1,2,4
      triazolo[1,5-c]pyrimidines, bearing oxygenated substituents on the phenylalkyl
      chains on the 7-position, have been synthesized. The compounds were tested in
      binding and functional assays to evaluate affinity, potency, and selectivity for
      rat A2A compared to rat A1 and human A3 receptor subtypes. The most interesting
      compounds (5d,e,h) were tested also in binding to human A1 and A2A adenosine
      receptors. They showed very good affinity (Ki = 0.94 nM for compound 5h) and
      interesting selectivity with respect to both rA1 and hA3 (compound 5h: rA1/rA2A =
      787, hA3/rA2A > 10 000). These important findings make this new series of
      compounds the first really selective for A2A adenosine receptors. Thermodynamic
      parameters were evaluated; all the tested compounds displayed an enthalpy-driven
      binding as expected for antagonists. Moreover, compound 5h showed a negative
      entropy value. The highly negative enthalpic and entropic contributions could
      mean that 5h fits very well in the binding site where, probably, an electrostatic
      interaction is present associated to a scarce solvent reorganization around the
      receptor binding site. These compounds deserve to be further developed to assess
      their potential for treatment of neurodegenerative disorders such as Parkinson's
      disease.

PMID- 9622555
TI  - Substituted naphthofurans as hallucinogenic phenethylamine-ergoline hybrid
      molecules with unexpected muscarinic antagonist activity.
AB  - A series of substituted racemic naphthofurans were synthesized as "hybrid"
      molecules of the two major prototypical hallucinogenic drug classes, the
      phenethylamines and the tryptamines/ergolines. Although it was hypothesized that
      these new agents might possess high affinity for the serotonin 5-HT2A/2C receptor
      subtypes, unexpected affinity for muscarinic receptors was observed. The
      compounds initially synthesized for this study were (+/-)-anti- and syn-4-amino-6
      methoxy-2a,3,4,5-tetrahydro-2H-naphtho[1,8-bc]furan (4a,b), respectively, and
      their 8-bromo derivatives 4c,d, respectively. The brominated primary amines 4c,d
      were assayed initially for activity in the two-lever drug discrimination (DD)
      paradigm in rats trained to discriminate saline from LSD tartrate (0. 08 mg/kg).
      Also, 4c,d were evaluated for their ability to compete against agonist and
      antagonist radioligands at cloned human 5-HT2A, 5-HT2B, and 5-HT2C receptors.
      After the syn diastereomers were found to have the highest activity in these
      preliminary assays, the N-alkylated analogues syn-N,N-dimethyl-4-amino-6-methoxy
      2a,3,4, 5-tetrahydro-2H-naphtho[1,8-bc]furan (4e) and syn-N, N-dipropyl-4-amino-6
      methoxy-2a,3,4,5-tetrahydro-2H-naphtho[1, 8-bc]furan (4f) were prepared and
      assayed for their affinities at [3H]ketanserin-labeled 5-HT2A and [3H]-8-OH-DPAT
      labeled 5-HT1A sites. All of the molecules tested had relatively low affinity for
      serotonin receptors, yet a preliminary screen indicated that compound 4d had
      affinity for muscarinic receptors. Thus, 4b,d,e were evaluated for their affinity
      at muscarinic M1-M5 receptors and also assessed for their functional
      characteristics at the M1 and M2 isoforms. Compound 4d had affinities of 12-33 nM
      at all of the muscarinic sites, with 4b,e having much lower affinity. All three
      compounds fully antagonized the effects of carbachol at the M1 receptor, while
      only 4d completely antagonized carbachol at the M2 receptor. The fact that the
      naphthofurans lack LSD-like activity suggests that they do not bind to the
      serotonin receptor in a way such that the tricyclic naphthofuran nucleus is
      bioisosteric with, and directly superimposable upon, the A, B, and C rings of
      LSD. This also implies, therefore, that the hallucinogenic phenethylamines cannot
      be directly superimposed on LSD in a common binding orientation for these two
      chemical classes, contrary to previous hypotheses.

PMID- 9622557
TI  - Antimalarial cyclic peroxy ketals.
AB  - Over 20 new, cyclic, peroxy ketals have been prepared via a two-step protocol
      starting with readily available aryl methyl ketones. Structure-activity
      correlations using in vitro antimalarial data as a guide for optimization of
      potency have led to the design and synthesis of seven new peroxides that have
      IC50 values of 31-85 nM (artemisinin IC50 = 8.4 nM). Some SAR generalizations are
      discussed.

PMID- 9622556
TI  - Development of orally active oxytocin antagonists: studies on 1-(1-[4-[1-(2
      methyl-1-oxidopyridin-3-ylmethyl)piperidin-4-yloxy]-2- methoxybenzoyl]piperidin-4
      yl)-1,4-dihydrobenz[d][1,3]oxazin-2-one (L-372,662) and related pyridines.
AB  - The previously reported oxytocin antagonist L-371,257 (2) has been modified at
      its acetylpiperidine terminus to incorporate various pyridine N-oxide groups.
      This modification has led to the identification of compounds with improved
      pharmacokinetics and excellent oral bioavailability. The pyridine N-oxide series
      is exemplified by L-372,662 (30), which possessed good potency in vitro (Ki = 4.1
      nM, cloned human oxytocin receptor) and in vivo (intravenous AD50 = 0.71 mg/kg in
      the rat), excellent oral bioavailability (90% in the rat, 96% in the dog), good
      aqueous solubility (>8.5 mg/mL at pH 5.2) which should facilitate formulation for
      iv administration, and excellent selectivity against the human arginine
      vasopressin receptors. Incorporation of a 5-fluoro substituent on the central
      benzoyl ring of this class of oxytocin antagonists enhanced in vitro and in vivo
      potency but was detrimental to the pharmacokinetic profiles of these compounds.
      Although lipophilic substitution around the pyridine ring of compound 30 gave
      higher affinity in vitro, such substituents were a metabolic liability and caused
      shortfalls in vivo. Two approaches to prevent this metabolism, addition of a
      cyclic constraint and incorporation of trifluoromethyl groups, were examined. The
      former approach was ineffective because of metabolic hydroxylation on the
      constrained ring system, whereas the latter showed improvement in plasma
      pharmacokinetics in some cases.

PMID- 9622558
TI  - Does the anti-hepatitis B virus activity of (+)-5'-noraristeromycin exist in its
      4'-epimer and 4'-deoxygenated derivatives?
AB  - To begin an exploration of the structural parameters responsible for the activity
      of (+)-5'-noraristeromycin toward hepatitis B virus (HBV), three derivatives
      varied at the C-4' position have been prepared and evaluated. The syntheses began
      with a Mitsunobu coupling reaction of an appropriate cyclopentanol with 6
      chloropurine. The products of these reactions were synthetically altered by
      standard ammonolysis and deprotection procedures to give the desired products.
      Evaluation of the new derivatives indicated that removal of the C-4' hydroxyl of
      (+)-5'-noraristeromycin increased its potency toward HBV by approximately 10
      fold.

PMID- 9622559
TI  - Determinants of Soil Microbial Communities: Effects of Agricultural Management,
      Season, and Soil Type on Phospholipid Fatty Acid Profiles

PMID- 9622560
TI  - Temporal Variations in Heterotrophic Mesophilic Bacteria from a Marine Shallow
      Hydrothermal Vent off the Island of Vulcano (Eolian Islands, Italy)

PMID- 9622561
TI  - Seasonal Variation in the Structure of a Marine Benthic Microbial Community

PMID- 9622562
TI  - Spatial Homogeneity of Abundant Bacterial 16S rRNA Molecules in Grassland Soils

PMID- 9622563
TI  - Phylogenetic Diversity of Archaea and Bacteria in a Deep Subsurface Paleosol

PMID- 9622565
TI  - Yeast Community Persistence in a Spatially Structured Environment

PMID- 9622564
TI  - Survival of Plasmid-Containing Bacillus subtilis Released into Mushroom Compost

PMID- 9622566
TI  - Bacterial Colonization and Ectoenzymatic Activity in Phytoplankton-Derived Model
      Particles. Part II. Cleavage and Uptake of Carbohydrates

PMID- 9622567
TI  - A Predictive Model of Bacterial Foraging by Means of Freely Released
      Extracellular Enzymes

PMID- 9622568
TI  - Dynamics of Dimethyl Sulfide in a Marine Microbial Mat

PMID- 9622569
TI  - Factors Affecting Attachment of Enterobacter cloacae to Germinating Cotton Seed

PMID- 9622570
TI  - Magnesium transport in freshwater teleosts 
AB  - The magnesium handling of freshwater teleost fish is discussed, with an emphasis
      on the role of branchial, intestinal and renal transport. In response to the
      eminent threat of constant diffusive losses of minerals such as magnesium,
      freshwater fish have developed efficient mechanisms for magnesium homeostasis.
      Magnesium losses are overcome by the uptake of magnesium from the food, making
      the intestine an important route for magnesium uptake. Some evidence suggests
      that intestinal magnesium uptake in fish is a regulated, cellular process. The
      ambient water is an additional magnesium source for fish, implicating the gills
      as a secondary route for magnesium uptake. Certainly, in some species, direct
      uptake from the water, probably via branchial routes, ameliorates the effects of
      a low-magnesium diet. The hard tissues, representing over 50 % of the total body
      magnesium pool, form a reservoir from which magnesium can be recruited to perform
      its functions in the cellular metabolism of soft tissues such as muscle. In fish,
      as in terrestrial vertebrates, the balance of a variety of elements becomes
      disturbed when the magnesium homeostasis of the soft tissues is disrupted.
      However, fish appear to be less sensitive than terrestrial vertebrates to these
      perturbations. Magnesium is reabsorbed in the kidneys to minimise losses. For
      renal cells, part of a cellular pathway has been elucidated that would allow
      absorptive magnesium transport (a magnesium conductive pathway in renal brush
      border membranes). In some euryhaline teleosts, the kidneys appear to switch
      instantaneously to rapid magnesium secretion upon magnesium loading, a response
      common to marine fish that are threatened by diffusive magnesium entry. This
      enigmatic mechanism underlies the capacity of some euryhaline species to
      acclimate rapidly to sea water. Despite the progress made over the last decade,
      much of the cellular and molecular basis of magnesium transport in the gills,
      intestine and kidneys remains obscure. The application of fluorescent,
      radioactive and molecular probes, some of which have only recently become
      available, may yield rapid progress in the field of magnesium research.

PMID- 9622571
TI  - Kinetic analysis of a signal-transduction pathway by time-resolved somatic
      complementation of mutants.
AB  - Sensory control of sporulation in Physarum polycephalum plasmodia is mediated by
      a branched signal-transduction pathway that integrates blue light, far-red light,
      heat shock and the starvation state. Mutants defective in the pathway were
      isolated and three phenotypes obtained: blue-blind, general-blind and light
      independent sporulating. When plasmodia of the blue-blind mutant Blu1 were
      exposed to a pulse of blue light and subsequently fused to non-induced wild-type
      plasmodia, the resulting heterokaryons sporulated, indicating a functional blue-
      light photoreceptor in the mutant. When the general-blind mutant Nos1 was fused
      to a wild-type plasmodium which had been induced by light, sporulation of the
      heterokaryon was blocked. However, the dominant inhibition of sporulation by Nos1
      was gradually lost with increasing time between induction by light and time of
      fusion, suggesting that Nos1 can be bypassed by the time-dependent formation of a
      downstream signal-transduction intermediate. Phenotype expression in
      constitutively sporulating (Cos) mutants depended on starvation. The Cos2 product
      was titrated by fusing mutant plasmodia of different sizes to wild-type plasmodia
      of constant size and analysing the sporulation probability of the resulting
      heterokaryon. The titration curve indicates that a small change in the amount of
      Cos2 product can cause sporulation. We conclude that somatic complementation
      analysis allows the time-resolved evaluation of the regulatory function of
      mutations in a signal-transduction pathway without prior cloning of the gene.
      This shortcut allows us to characterize many mutants quickly and to select those
      for molecular analysis that display a well-defined regulatory function.

PMID- 9622572
TI  - Organic matrix synthesis in the scleractinian coral stylophora pistillata: role
      in biomineralization and potential target of the organotin tributyltin 
AB  - The kinetics of organic matrix biosynthesis and incorporation into scleractinian
      coral skeleton was studied using microcolonies of Stylophora pistillata.
      [14C]Aspartic acid was used to label the organic matrix since this acidic amino
      acid can represent up to 50 mol % of organic matrix proteins. External aspartate
      was rapidly incorporated into tissue protein without any detectable lag phase,
      suggesting either a small intracellular pool of aspartic acid or a pool with a
      fast turn-over rate. The incorporation of 14C-labelled macromolecules into the
      skeleton was linear over time, after an initial delay of 20 min. Rates of
      calcification, measured by the incorporation of 45Ca into the skeleton, and of
      organic matrix biosynthesis and incorporation into the skeleton were constant.
      Inhibition of calcification by the Ca2+ channel inhibitor verapamil reduced the
      incorporation of organic matrix proteins into the skeleton. Similarly, organic
      matrix incorporation into the skeleton, but not protein synthesis for
      incorporation into the tissue compartment, was dependent on the state of
      polymerization of both actin and tubulin, as shown by the sensitivity of this
      process to cytochalasin B and colchicin. These drugs may inhibit exocytosis of
      organic matrix proteins into the subcalicoblastic space. Finally, inhibition of
      protein synthesis by emetin or cycloheximide and inhibition of N-glycosylation by
      tunicamycin reduced both the incorporation of macromolecules into the skeleton
      and the rate of calcification. This suggests that organic matrix biosynthesis and
      its migration towards the site of calcification may be a prerequisite step in the
      calcification process. On the basis of these results, we investigated the effects
      of tributyltin (TBT), a component of antifouling painting known to interfere with
      biomineralization processes. Our results have shown that this xenobiotic
      significantly inhibits protein synthesis and the subsequent incorporation of
      protein into coral skeleton. This effect was correlated with a reduction in the
      rate of calcification. Protein synthesis was shown to be the parameter most
      sensitive to TBT (IC50=0.2 micromol l-1), followed by aspartic acid uptake by
      coral tissue (IC50=0.6 micromol l-1), skeletogenesis (IC50=3 micromol l-1) and
      Ca2+ uptake by coral tissue (IC50=20 micromol l-1). These results suggest that
      the mode of action of TBT on calcification may be the inhibition of organic
      matrix biosynthesis.

PMID- 9622573
TI  - Elevated 5'-nucleotidase and alkaline phosphodiesterase activities in trout gill
      localize to endothelial (pillar) cells 
AB  - Tissue homogenates from rainbow trout gill had three- to fivefold higher specific
      activity for 5'-nucleotidase (5'NT) and more than twofold greater alkaline
      phosphodiesterase (APD) activity than liver or kidney homogenates. In isolated
      plasma membranes, gill 5'NT activity was 3-5 times greater than that of the
      kidney or liver; gill and kidney plasma membranes had similar APD specific
      activities, both more than five times that of liver. 5'NT and APD activities were
      localized by histochemistry to the endothelial (pillar) cells of trout gill
      secondary lamellae. Staining was consistent with the concentration of both
      activities at the apical plasma membranes of pillar cells (i.e. at the lamellar
      microvascular surfaces). This localization may reflect a capacity for processing
      nucleotide metabolites circulating in the blood, perhaps relating to purinergic
      regulation of local lamellar hemodynamics. There was no histochemical evidence of
      either 5'NT or APD activity in the gill epithelial (pavement) cells that
      interface directly with the environment. In contrast, in trout kidney, both
      enzyme activities localized to the apical region of tubule epithelial cells. The
      absence of 5'NT and APD activity in pavement cells reinforces the unique
      structural and functional character of the gill-environment epithelial barrier.
      The results indicate that 5'NT and APD activities have particular potential
      application as markers in efforts to isolate and characterize specific gill
      plasma membrane fractions.

PMID- 9622574
TI  - Contralateral coordination and retargeting of limb movements during scratching in
      the locust 
AB  - Locusts, Schistocerca gregaria, in common with many limbed vertebrates, can make
      directed scratching movements in response to tactile stimulation. For instance,
      stimulation of different sites on a wing elicits different movements that are
      accurately targeted so that the hindleg tarsus passes across the stimulus site. I
      have analysed these limb movements to define the ability of a locust to target
      stimulus sites correctly under a range of experimental conditions. In particular,
      I describe aspects of the behaviour that reveal possible neuronal pathways
      underlying the responses. These neuronal pathways will be the subject of further
      physiological analyses. Limb targeting during scratching is continuously graded
      in form; different patterns of movement are not separated by sharp transitions.
      The computation of limb trajectory takes into account the starting posture of the
      hindleg, so that different trajectories can be used to reach a common stimulus
      site from different starting postures. Moreover, the trajectories of the two
      hindlegs moving simultaneously from different starting postures in response to a
      single stimulus can be different, so that their tarsi converge onto the common
      stimulus site. Different trajectories can be used to reach a common stimulus site
      from the same start posture. Targeting information from a forewing is passed not
      only down the nerve cord to the ipsilateral hindleg but also across the nerve
      cord, so that the contralateral hindleg can also make directed movements. This
      contralateral transmission does not rely on peripheral sensory feedback. When the
      stimulus site moves during a rhythmical scratch, the targeting of subsequent
      cycles reflects this change. Both ipsilateral and contralateral hindlegs can
      retarget their movements. The trajectory of a single cycle of scratching directed
      towards a particular stimulus site can be modified after it has begun, so that
      the tarsus is redirected towards a new stimulus site.

PMID- 9622575
TI  - A genetic deficiency that spans the flightin gene of Drosophila melanogaster
      affects the ultrastructure and function of the flight muscles.
AB  - We have developed a reverse-genetic approach to study the function of flightin, a
      unique protein of the flight muscle myofibril of Drosophila melanogaster. We
      describe the generation and characterization of Df(3L)fln1, a lethal genetic
      deficiency in the 76BE region of the third chromosome which deletes several
      genes, including the gene for flightin. We show that heterozygous flies harboring
      the Df(3L)fln1 mutation exhibit both impaired flight and ultrastructural defects
      in their flight muscle myofibrils. We found that the mutation does not interfere
      with assembly of the myofibril but leads to disorganization of peripheral
      myofilaments in adult myofibrils. Most myofibrils, nevertheless, retain an intact
      core that represents approximately 80 % of the normal lattice diameter.
      Mechanical analysis of single skinned flight muscle fibers demonstrates that the
      mutation has no significant effect on net power output but increases the
      frequency at which maximum power is delivered to the wings, potentially reducing
      the overall performance of the flight system. The results suggest that flightin
      is an indispensable part of the flight muscle contractile mechanism.

PMID- 9622576
TI  - Partitioning the effects of temperature and kinematic viscosity on the C-start
      performance of adult fishes 
AB  - Temperature has been shown to have a significant effect on swimming performance
      in teleost fish. This thermal dependence has usually been attributed to
      correlated changes in muscle contractile physiology. However, the physical
      properties of all materials, including both water and living tissues, are
      profoundly affected by changes in temperature. In particular, both the kinematic
      viscosity of water and the flexible body dynamics of the fish (independent of
      muscle contractile activity) are substantially higher at lower temperatures. In
      this study, we investigated the extent to which the observed thermal dependence
      of locomotor performance of fish simply reflects changes in the biophysical
      properties of the aqueous medium independent of the changing physiology of the
      animals. C-starts (escape swimming) of adult goldfish (Carassius auratus, length
      approximately 8 cm) were video-taped (400 frames s-1) at 5 degreesC and 20
      degreesC in fresh water and at 20 degreesC in fresh water containing 1.2 %
      dextran (kinematic viscosity equivalent to that of water at 5 degreesC).
      Temperature had a significant positive effect on maximum forward velocity (m s
      1), angular velocity (degrees s-1) and total distance moved, but viscosity had no
      detectable effect on any kinematic parameters at 20 degreesC. Since viscous
      forces may have more pronounced effects on smaller fish, C-starts of adult
      guppies (Poecilia reticulata, length approximately 2 cm) were video-taped in
      fresh water and in fresh water containing 1.2 % and 3. 6 % dextran at 20
      degreesC. Viscosity had a significant effect on kinematic variables only at 3.6 %
      dextran; at 1.2 % dextran, the effects were marginal. It was concluded that most
      of the observed thermal dependence of C-starts at temperatures normally
      experienced by these fish was due to changes in physiological processes as
      opposed to physical changes in the environment.

PMID- 9622577
TI  - The characterization of presynaptic octopamine receptors modulating octopamine
      release from an identified neurone in the locust 
AB  - Octopamine release has been demonstrated from the dorsal unpaired median neurone
      to the locust extensor-tibiae muscle (DUMETi) in response to high-[K+] saline.
      Here, we provide evidence for the existence of presynaptic inhibitory
      autoreceptors for octopamine on the DUMETi terminals and report on their
      pharmacological profile. Octopamine release was initiated by exposure to high
      [K+] saline (0. 1 mol l-1) and measured using a radioenzyme assay for octopamine.
      Octopamine receptor antagonists (10(-4 )mol l-1) potentiated the high-[K+]
      mediated release of octopamine with the following rank order of potency:
      phentolamine = metoclopramide > mianserin = chlorpromazine > cyproheptadine >
      yohimbine. Octopamine receptor agonists (10(-4 )mol l-1) inhibited the high-[K+]
      mediated release of octopamine with the following rank order of potency:
      naphazoline > tolazoline > clonidine. Thus, the octopamine autoreceptors on the
      DUMETi terminals are much closer pharmacologically to the pre-and postsynaptic
      OCTOPAMINE2 receptors in the locust extensor-tibiae muscle preparation than to
      the OCTOPAMINE3 receptors from the locust central nervous system. The results
      suggest that there is likely to be more than one type of insect neuronal
      octopamine receptor. It is also likely that presynaptic modulation of octopamine
      release may be confined to octopamine receptors since a wide range of other
      putative modulatory substances did not produce this effect.

PMID- 9622578
TI  - Diving speeds and angles of a gyrfalcon (Falco rusticolus) 
AB  - An optical tracking device recorded the three-dimensional paths of 11 dives by a
      1.02 kg gyrfalcon, trained to dive to a falconer. The dives started at altitudes
      up to 500 m above the ground and were inclined at angles of 17-62 degrees from
      the horizontal. The falcon controlled its speed during the dives, rather than
      simply falling from the sky, and the dives had three phases. During the first
      (acceleration) phase, the falcon accelerated to speed limits between 52 and 58 m
      s-1 in the seven fastest dives, evidently with minimum drag, because its
      accelerations were close to those predicted from theory for minimum drag. The
      falcon then began a constant-speed phase by increasing drag by a factor of 1.3
      4.8 while still 100-350 m above the ground in most dives. The constant-speed
      phase lasted no more than a few seconds, and the falcon then began a deceleration
      phase by increasing its drag further, this time by factors of 1.7-3. 2, and
      decelerating with a mean value of -0.95 times gravitational acceleration. During
      all three phases, the dive angle was nearly constant or increased during the
      deceleration phase, and the falcon made no changes in its body shape that were
      obvious through the tracking device telescope except to reduce its wing span as
      it accelerated. The falconer, however, was close to the falcon at the end of the
      dive and could see that, during the deceleration phase, the falcon held its wings
      in a cupped position, apparently with a high angle of attack and therefore high
      drag. At the end of the deceleration phase, the falcon dropped its legs, spread
      its toes and finally spread its wings as it approached the falconer. Although the
      speeds reported here are the fastest ever measured with known accuracy in
      animals, the falcon could theoretically have reached more than 70 m s-1 if it had
      continued to accelerate with minimum drag until close to the ground. Even at this
      speed, it would have had enough altitude to pull out of the dive before crashing
      into the ground. Several authors have estimated that diving falcons reach speeds
      of more than 70 m s-1, and wild falcons may reach such speeds when they make
      long, steep dives upon birds flying high in the air.

PMID- 9622579
TI  - Mechanics and energetics of human locomotion on sand.
AB  - Moving about in nature often involves walking or running on a soft yielding
      substratum such as sand, which has a profound effect on the mechanics and
      energetics of locomotion. Force platform and cinematographic analyses were used
      to determine the mechanical work performed by human subjects during walking and
      running on sand and on a hard surface. Oxygen consumption was used to determine
      the energetic cost of walking and running under the same conditions. Walking on
      sand requires 1.6-2.5 times more mechanical work than does walking on a hard
      surface at the same speed. In contrast, running on sand requires only 1.15 times
      more mechanical work than does running on a hard surface at the same speed.
      Walking on sand requires 2.1-2.7 times more energy expenditure than does walking
      on a hard surface at the same speed; while running on sand requires 1.6 times
      more energy expenditure than does running on a hard surface. The increase in
      energy cost is due primarily to two effects: the mechanical work done on the
      sand, and a decrease in the efficiency of positive work done by the muscles and
      tendons.

PMID- 9622580
TI  - The effects of increased protein intake on kidney size and function.
AB  - In endothermic vertebrates, long-term increases in metabolic energy demand are
      often associated with increases in food intake and accompanied by increases in
      organ mass. Wide-scale increases in organ mass have often been attributed to a
      metabolic response to increased energy intake and utilization. On a constant
      diet, however, increased food intake is also associated with increased protein
      intake. We hypothesized that, while increased food intake itself may be
      responsible for increases in digestive tract mass, the consequent increased
      protein intake would be the factor responsible for increased kidney mass and
      function. Thus, we exposed male and female mice to diets differing in protein
      level (7 %, 15 % or 46 % casein by mass) at different acclimation temperatures (5
      degrees C or 23 degrees C). Within an acclimation temperature, food intake rate
      remained constant over the entire range of dietary protein level, and protein
      intake rate increased as dietary content increased. The mice in the cold
      acclimation group increased food intake rate by 48-120 % over those in the warm
      acclimation group. Liver, kidney and stomach mass increased with protein intake
      rate, while digestive tract and other vital organ masses increased only in
      response to increased energy intake rate. Blood urea nitrogen levels increased
      with protein intake rate. Glomerular filtration rates increased with increases in
      dietary protein level in male mice but not female mice. Finally nitrogen
      filtration rate increased with protein intake rate for mice on the high-protein
      diet. We suggest that it is primarily the increased protein intake rate rather
      than the increased food intake rate that results in the changes in kidney and
      liver mass and kidney function observed to occur in situations of high energy
      demand.

PMID- 9622581
TI  - Rise of intracellular free calcium levels with activation of inositol
      triphosphate in a human colonic carcinoma cell line (COLO 205) by heat-stable
      enterotoxin of Escherichia coli.
AB  - The heat-stable enterotoxin (STa) produced by Escherichia coli has been found to
      increase rapidly two potential intracellular signals, inositol triphosphate and
      cytosolic free calcium in a human colonic cell line, COLO 205. Addition of STa to
      COLO 205 cells prelabelled with myo-[2-3H]inositol resulted in a rapid rise of
      [3H]inositol triphosphate. Using fluorescent indicator, Fura-2AM, intracellular
      free Ca2+ has been found to increase 5.12-fold compared to control. Suspension of
      cells in calcium-free buffer demonstrated STa-induced rapid rise of cytosolic
      Ca2+. The same result was found when extracellular calcium was chelated with
      EGTA. This effect was not observed with cells that were pretreated with
      dantrolene which suggest that the intracellular calcium rise might be due to
      mobilization from intracellular stores. This study demonstrated for the first
      time a change in cytosolic calcium in cultured human colonic cells by STa, which
      is accompanied by inositol triphosphate activation.

PMID- 9622582
TI  - Histological and temporal characteristics of nigral transneuronal degeneration
      after striatal injury.
AB  - Neurotoxic injury of the caudate-putamen and lateral globus pallidus unilaterally
      initiated transneuronal degeneration of neurons in the ipsilateral substantia
      nigra reticulata (SNR). Quantification of SNR neurons using unbiased stereology
      demonstrated that neuron loss began 4 days after the initial striatal lesion,
      followed by significant loss (50%) at 6 days and a plateau at 8 days. Analysis at
      the light and ultrastructural levels revealed morphological changes consistent
      with a type of programmed cell death. These temporal and histological results
      refine an in vivo model in which to explore mechanisms of delayed neuronal
      degeneration.

PMID- 9622583
TI  - The biochemical inhibition mode of bredinin-5'-monophosphate on DNA polymerase
      beta.
AB  - We reported previously [T. Horie, Y. Mizushina, M. Takemura, F. Sugawara, A.
      Matsukage, S. Yoshida, K. Sakaguchi, Int. J. Mol. Med., 1 (1998) 83-90.] that a
      5'-monophosphate form (breMP) of bredinin, which has been used clinically as an
      immunosuppressive drug, selectively suppressed the activities of mammalian DNA
      polymerase alpha (pol. alpha) and beta (pol. beta). In a preliminary study of the
      action mode, for pol. beta, breMP acted by competing with, unexpectedly, not only
      the substrate but also with the template-primer. The mode might be attributable
      to the structure and function of pol. beta itself. We therefore investigated the
      biochemical inhibition mode of pol. beta in more detail by using two pol. beta
      fragments which were proteolytically separated into the template-primer-binding
      domain and the catalytic domain. BreMP inhibited only the catalytic activity of
      the catalytic domain fragment, and could not bind to the template-primer-binding
      domain fragment, suggesting that it directly competes with the substrate at its
      binding site of the catalytic domain, and indirectly, but simultaneously and
      competitively disturbs the template-primer incorporation into the template-primer
      binding domain.

PMID- 9622584
TI  - The E6 and E7 genes of human papilloma virus-type 16 protect primary astrocyte
      cultures from injury.
AB  - Many oncogenes are implicated in the regulation of apoptosis as well as in
      control of the cell cycle, and several have been shown to protect cells from
      injury. We tested whether the expression of human papillomavirus type 16 genes E6
      and E7 could protect primary astrocytes from injury. Retroviral vectors were used
      to express E6, E7, or E6E7 in primary murine astrocyte cultures. Astrocytes
      expressing E6E7 suffered less than half the injury seen in controls after
      exposure to 400 microM H2O2. When we compared astrocytes expressing only E6 or
      E7, cells expressing E7 alone were protected to a greater extent and from more
      severe injury than those expressing E6. E6E7, E6 and E7 all provided protection
      from 30 h glucose deprivation, but again E7 provided the best protection,
      reducing injury to less than a third of that seen in controls. Expression of E7
      alone decreases vulnerability to both hydrogen peroxide and glucose deprivation
      injury while E6 alone primarily decreases glucose deprivation injury. These
      results demonstrate that expression of human papillomavirus oncogenes can reduce
      the vulnerability of astrocytes to oxidative stress and nutrient deprivation.

PMID- 9622585
TI  - Mitochondrial protein import in animals.

PMID- 9622586
TI  - Induction of heme oxygenase-1 (HO-1) in the contused spinal cord of the rat.
AB  - The induction of heme oxygenase-1 (HO-1) was studied in intact spinal cords and
      injured spinal cords after a moderate, thoracic contusion injury. HO-1 was
      immunolocalized in the normal cord and along the axis of the cord at 1, 2, 3 and
      4 days after contusion. Induction of this enzyme in astrocytes and
      microglia/macrophages was evaluated using immunofluorescent double labeling with
      monoclonal antibodies to HO-1 and either glial fibrillary acidic protein or the
      complement C3bi receptor. HO-1 was expressed in neurons in the normal spinal
      cord. After contusion, HO-1 was induced in both gray and white matter at the
      impact site. In segments of cord that were 1 cm proximal or distal to the injury,
      HO-1 was primarily induced in the dorsal columns and occasionally in the lateral
      white matter. This pattern of induction was noted at all time points. The HO-1
      was induced primarily in microglia/macrophages. The distribution of the HO-1
      positive cells closely correlated with the pattern of intraparenchymal
      hemorrhage. These findings demonstrate acute induction of HO-1 in non-neuronal
      cells in the injured spinal cord. Induction of HO-1 in glia may be a consequence
      of multiple factors including exposure to heme proteins, hypoxia and oxidative
      stress.

PMID- 9622587
TI  - Movement-induced modulation of soleus H reflexes with altered length of
      biarticular muscles.
AB  - Passive pedaling movements of the leg results in the phasic modulation of the
      soleus H reflex of that leg. In contrast, the H reflex of the contralateral leg
      is attenuated tonically. The phasic modulation of the reflex ipsilaterally can be
      attributed to the afferent discharge associated with the cyclic lengthening of
      the extensor muscles. We hypothesized that the tonic attenuation of the
      contralateral reflex could be explained if the afferent feedback arising from the
      lengthening of the biarticular muscles had an increased importance in regulating
      the amplitude of the contralateral reflex. To test this, the passive pedaling
      movements were reduced to those about either the knee or hip alone. Despite the
      alteration in the pattern of stretching of the biarticular muscles, the
      contralateral soleus H reflex was tonically attenuated during both forms of
      single joint movements. We suggest that the same phasic afferent discharge
      responsible for the modulation of the ipsilateral soleus H reflex initiates the
      tonic attenuation contralaterally, but that the signal undergoes a complex
      transformation in crossing the cord. These results do not rule out the
      possibility that the stretching of the biarticular muscles contributes to the
      attenuation of the ipsilateral soleus H reflex, which is subsequently masked by a
      powerful influence from the stretching of the uniarticular extensor muscles. To
      test this possibility, a second experiment manipulated the lengths of the muscles
      of the leg by altering the positions of the static joints during isolated
      rotation of either the knee or hip and measuring the amplitude of the ipsilateral
      soleus H reflex. From the results, it was clear that stretching the uniarticular
      extensor muscles produced the most dramatic effects. However, the stretch of the
      biarticular muscles yielded mild inhibitory influences if these muscles were near
      their maximal lengths.

PMID- 9622588
TI  - Induction of calponin-h1 by transforming growth factor-beta1 in cultured human
      ito cells, LI90.
AB  - We investigated the effect of transforming growth factor-beta1 (TGF-beta1) on the
      expression of calponin-h1, alpha-smooth muscle actin (alpha-SMA), and
      extracellular matrix (ECM) components in a cultured human Ito cell line, LI90.
      The TGF-beta1 treatment stimulated productions of hyaluronic acid and laminin,
      and significantly decreased the secretion of hepatocyte growth factor in LI90
      cells. The functional characteristics of LI90 cells were compatible with those of
      human-activated Ito cells that are known as pericyte-like mesenchymal liver
      cells. TGF-beta1 induced a slight growth-inhibition of LI90 cells. TGF-beta1
      enhanced the expressions of both alpha-SMA and calponin-h1 at the protein level,
      while tumor necrosis factor-alpha and interleukin-1alpha did not affect the
      expressions of these cytoskeletal proteins on LI90 cells. The addition of TGF
      beta1 to LI90 cells resulted in a significant increase of calponin-h1 mRNA
      levels, but not calponin-h2. These data suggest that the expression of calponin
      h1 is controlled at the level of mRNA under the coordinate regulation together
      with alpha-SMA as the process of perpetuation of activated Ito cells promoted by
      TGF-beta1. The identification of smooth muscle features promoted by TGF-beta1
      support the hypothesis that the activation of Ito cells coincides with their
      contractile behavior, indicating that these cells may be important in
      vasoregulation during liver injury and fibrosis.

PMID- 9622589
TI  - Local control of alpha1-proteinase inhibitor levels: regulation of alpha1
      proteinase inhibitor in the human cornea by growth factors and cytokines.
AB  - Alpha 1-proteinase inhibitor is a major serine proteinase inhibitor in the human
      cornea involved in the protection of the avascular corneal tissue against
      proteolytic damage. This inhibitor is upregulated systemically during infection,
      inflammation and injury. Cytokines that mediate the acute phase response such as
      IL-1beta and IL-2 increased alpha1-proteinase inhibitor present in corneal organ
      culture media. This released inhibitor represented mainly newly synthesized
      protein. However, IL-6, a general inducer of the acute phase response that
      upregulates alpha1-proteinase inhibitor in all other tissues and cells tested,
      failed to alter corneal alpha1-proteinase inhibitor levels over the tested period
      of 24 h. In addition to IL-1beta and IL-2, alpha1-proteinase inhibitor levels in
      the corneal organ culture medium increased following the addition of FGF-2 and
      IGF-I. The effect of the above growth factors and cytokines was relatively fast
      with maximal induction observed within the first 5 h. Among the tested growth
      factors and cytokines, IL-1beta was the most potent and increased total corneal
      alpha1-proteinase inhibitor levels approximately 2.4-fold in the cornea organ
      culture medium. Newly, synthesized alpha1-proteinase secreted into the medium
      increased 3.9-fold. In addition to the effect on corneal alpha1-proteinase
      inhibitor, IL-1beta also increased the amount of alpha1-proteinase inhibitor
      released by monocytes and macrophages but not by HepG2, CaCo2, and MCF-7 cells
      within 24 h. These results suggest that the cornea can locally control levels of
      alpha1-proteinase inhibitor in response to an inflammatory insult.

PMID- 9622590
TI  - Effects of SFO lesion or captopril on drinking induced by intragastric hypertonic
      saline.
AB  - This study examined the hypothesis that the subfornical organ (SFO), a
      circumventricular organ with both osmosensitive elements and dipsogenic receptors
      for circulating angiotensin (ANG) II, is important for the water drinking
      response that follows an intragastric (ig) load of hypertonic NaCl. A 2-ml saline
      load was administered ig at 300, 900, or 1200 mOsm/kg to rats with sham lesions
      or lesions of the SFO, and intake was measured periodically for 2 h. Hypertonic
      loads caused sham-lesioned rats, but not SFO-lesioned rats, to drink earlier in
      the test or to drink more water than did the isotonic load. Inhibition of ANG II
      synthesis in unoperated rats with 100 mg/kg of captopril reduced water intake
      only during the initial 15 min after a gavage of 1200 mOsm/kg saline. Loads of
      900 and 1200 mOsm/kg both increased plasma osmolality and sodium concentration by
      15 min after gavage without greatly affecting hematocrit or plasma protein
      concentration. Thus, the SFO is important for the osmotically-induced water
      drinking response after acute ig administration of hypertonic saline. With the
      possible exception of the first 15 min, this drinking response is independent of
      the peripheral synthesis of ANG II.

PMID- 9622591
TI  - Regeneration of the rat sciatic nerve into allografts made acellular through
      chemical extraction.
AB  - The aim of this study was to develop a procedure by which myelin and Schwann
      cells could be removed from a peripheral nerve while the basal lamina tubes,
      remained intact, and to test if such preparations could be used as allografts for
      the repair of a gap in the continuity of the rat sciatic nerve. We found that
      extraction with the detergents Triton X-100 and deoxycholate resulted in
      acellular nerve segments with preserved basal lamina tubes, here defined as the
      tubes which surrounds the axon/Schwann cell units. The morphology of the
      acellular nerve segments was revealed by scanning electron microscopy, teasing,
      immunohistochemistry and electrophoresis. Such grafts when allografted between
      two outbred rat strains, were found to support outgrowth of axons and migration
      of Schwann cells, which reoccupied the empty basal lamina tubes without excessive
      signs of inflammation. This new paradigm offers a possible solution to the major
      shortcomings of autologous nerve grafts, i.e., the requirement to sacrifice a
      healthy nerve and the shortage of graft material available for repair.

PMID- 9622592
TI  - Regulation of the cellular expression of secretory and cytosolic phospholipases
      A2, and cyclooxygenase-2 by peptide growth factors.
AB  - Secretory group II (sPLA2) and cytosolic (cPLA2) phospholipases A2 and
      cyclooxygenase-2 (Cox-2) play a pivotal role in release of proinflammatory
      eicosanoids. Excessive activity of sPLA2 per se can also propagate inflammation.
      Endogenous control of the above enzymes has not been completely elucidated. We
      investigated the combined impact of promoting cytokines and inhibitory peptide
      growth factors on the expression of mRNA of the above enzymes, on protein content
      and extracellular release of sPLA2 and on PGE2 production in osteoblasts (FRCO).
      The synthesis and release of sPLA2 were enhanced by about 20-fold by 0.5 ng/ml IL
      1beta or by 50 ng/ml of TNFalpha. Coaddition of both cytokines resulted in
      synergistic 150-fold increase in the release of sPLA2 implying the existence of
      two paths of induction. IL-1beta and TNFalpha markedly enhanced the transcription
      of sPLA2 mRNA. Kinetic study showed that IL-1/TNF initiated sPLA2 release after
      12 h, reaching maximum at 48 h. IL-1alpha was a weak stimulator of sPLA2 release,
      whereas IL-6, IL-8, IGF, IFN-gamma, growth hormone, insulin and GM-CSF were not
      stimulatory. Peptide growth hormones TGFbeta, PDGF-BB, EGF and bFGF markedly
      inhibited the extracellular release of sPLA2. TGFbeta and PDGF-BB significantly
      reduced the level of sPLA2 mRNA, thus acting upon transcription whereas EGF and
      bFGF were not inhibitory, acting rather upon the translational or
      posttranslational steps. IL-1/TNF and growth factors had no significant effect on
      cPLA2 mRNA expression. Cox-2 mRNA expression was markedly enhanced by IL-1/TNF
      and suppressed by all growth factors tested. Cytokines enhanced the extracellular
      release of PGE2 and further enhancement was induced by growth factors with the
      exception of TGFbeta. Cycloheximide abolished completely the release of sPLA2 and
      markedly reduced the release of PGE2 from cytokine-stimulated FRCO, regardless of
      whether growth factors were present or not. NS-398, a specific inhibitor of Cox-2
      abolished almost completely the release of PGE2 from cytokine-stimulated cells,
      regardless of the presence of growth factors. Thus, different signalling
      mechanisms are involved in the impact of growth factors on mRNA expression of
      sPLA2, cPLA2 and Cox-2. The differences between the impact on FRCO sPLA2 and that
      reported in other cells, imply that endogenous control of arachidonic acid
      cascade is cell-specific.

PMID- 9622593
TI  - Upregulation of striatal D2 receptors in the MPTP-treated vervet monkey is
      reversed by grafts of fetal ventral mesencephalon: an autoradiographic study.
AB  - Although neural transplantation holds promise as a treatment for Parkinson's
      disease, parkinsonian primates have generally exhibited inconsistent and
      incomplete recovery of motor functions following intrastriatal grafting of fetal
      ventral mesencephalon. One possible contributing factor to this variable response
      is lack of appropriate integration of donor neurons with host striatal circuitry
      with the result that there is insufficient dopamine release and postsynaptic
      dopamine receptor activation. This issue was examined by measuring the effect of
      transplanting fetal ventral mesencephalon to the striatum of 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine-treated (MPTP) monkeys on striatal D2 receptor
      binding. One year after receiving MPTP, D2 receptor binding was upregulated in
      the dorsal and ventral striatum of African green monkeys. Grafting of fetal
      ventral mesencephalon to the dorsal striatum of MPTP-treated monkeys 9 months
      before sacrifice, eliminated the D2 receptor upregulation in dorsal, but not
      ventral, region. Dopamine concentration in dorsal striatum of grafted MPTP
      treated monkeys was significantly higher than in that region of MPTP-treated non
      grafted monkeys. In addition, dopamine concentration was significantly higher in
      dorsal compared to ventral striatum of grafted MPTP-treated monkeys. These data,
      in addition to those from a previous autoradiographic study on dopamine uptake
      site density in these monkeys, strongly supports the hypothesis that ectopically
      placed ventral mesencephalon not only produces, but maintains the release of
      sufficient levels of dopamine to restore postsynaptic dopamine transmission in
      regions influenced by graft-derived dopamine.

PMID- 9622594
TI  - A microspectrophotometric study on the physicochemical properties of antipyrylazo
      III injected into rat myoballs for measuring free magnesium ion.
AB  - The accurate measurement of the intracellular concentration of free magnesium
      ions ([Mg2+]i) is essential for evaluating the role of Mg2+ in cellular
      functions. Among the specific (compared to fluorescent indicators) metallochromic
      dyes, antipyrylazo III (APIII) appears to be most suitable for measuring such
      concentrations in vertebrate cells according to in vitro studies. In this work,
      the intracellular physicochemical properties of APIII as a Mg2+ indicator were
      investigated in the cultured rat myoball by means of a microspectrophotometric
      technique, in order to obtain an accurate measurement of [Mg2+]i. A set of
      intracellular APIII-Mg2+ calibration spectra was established after
      permeabilization of the cell membrane with saponin. In comparison with recordings
      obtained in K+ solutions, the APIII absorption spectra recorded on a myoball
      exhibited a red shift and an overall change in absorbance, similar to that
      observed in a protein (bovine serum albumin: BSA) solution. The apparent
      dissociation constant of APIII for Mg2+ in the myoplasm was found to be 3.16 mM,
      significantly higher than the 1.86 mM measured in K+ solutions at the same pH
      (7.35). A stoichiometric ratio of 1:1 was found, however, both in solution and in
      the myoplasm. In addition, the injected APIII significantly affected the [Mg2+]i
      of myoballs. The [Mg2+]i was found to be 0.9+/-0.18 mM in 85 myoballs, on the
      basis of the intracellular calibration spectra obtained at the same myoplasmic
      APIII concentration ( approximately 2.5 mM), and after correction for the
      perturbing effect of the dye. It is concluded that an intracellular calibration
      and recording of whole spectrum are essential for proper interpretations of
      intracellular dye signals.

PMID- 9622595
TI  - Protective effects of free radical inhibitors in intracerebral hemorrhage in rat.
AB  - Iron compounds formed in the degradation of a hematoma can accelerate the
      formation of free radicals in adjacent ischemic or hypoperfused tissue. The
      purpose of this study was to examine the efficacy of compounds that quench free
      radicals in improving the outcome in rats with experimental intracerebral
      hemorrhage. Intracerebral hemorrhage was induced in rats by injection of
      bacterial collagenase and heparin into the caudate nucleus. Rats were treated
      with alpha-tocopherol plus ascorbic acid starting before hemorrhage, or with
      dimethylthiourea or alpha-phenyl-N-tert-butyl nitrone starting 2 h after
      hemorrhage, with treatment continued for 10 days after induction of hemorrhage.
      Outcome was assessed by behavioral analyses, magnetic resonance imaging, and
      histopathology. A trend towards behavioral improvement was found for rats treated
      with alpha-tocopherol/ascorbic acid, while behavior was significantly improved
      following intracerebral hemorrhage in rats treated with dimethylthiourea or alpha
      phenyl-N-tert-butyl nitrone. These results suggest that free radicals may play a
      role in the development of brain injury following intracerebral hemorrhage, and
      that compounds that interrupt the free radical cascade may improve outcome.
      However, treatment did not significantly affect edema, resolution of the
      hematoma, or neuronal injury in tissue adjacent to the hemorrhage.

PMID- 9622596
TI  - The development of cocaine-induced behavioral sensitization is affected by
      discrete quinolinic acid lesions of the prelimbic medial prefrontal cortex.
AB  - The brain circuitry thought to be involved in the development of behavioral
      sensitization to psychostimulants consists of the mesocorticolimbic dopaminergic
      system and its afferent and efferent structures, including the medial prefrontal
      cortex (mPFC). The mPFC can be further subdivided into several regions, one of
      which being the prelimbic area (PL). This study sought to examine the role that
      the PL mPFC plays in the development of cocaine-induced behavioral sensitization.
      Intact and lesioned animals were treated with cocaine (10 mg/kg) or saline once
      daily for 14 days and tested in an open field and in a 'sniffing box' on day 1,
      and then again on day 16, 48 h after the last drug injection. Behavioral
      parameters analyzed included locomotion, rearing, sniffing and grooming. It was
      found that the lesion affected the development of sensitization to cocaine. In
      the open field, lesioned animals showed a smaller increase in locomotion and
      rearing, but a larger increase in grooming as compared to the intact animals.
      While total sniffing scores in the sniffing box remained unchanged with repeated
      cocaine in the non-lesioned group, the lesioned group showed a decrease in
      sniffing. Finally, similar to what was seen in the open field, lesioned rats
      showed a strong tendency towards increased grooming. These results show that
      small discrete lesions of the PL mPFC can affect the development of behavioral
      sensitization to cocaine in a characteristic way. It is suggested that this
      effect might be mediated by the destruction of descending glutamatergic
      projections from the mPFC to the ventral tegmental area and/or nucleus accumbens.

PMID- 9622597
TI  - Characterization of a chloroplast isoform of serine acetyltransferase from the
      thermo-acidiphilic red alga Cyanidioschyzon merolae.
AB  - We isolated a gene for serine acetyltransferase (SAT), a key enzyme in sulfate
      assimilation, from the primitive red alga Cyanidioschyzon merolae, an inhabitant
      of sulfurous hot springs, and designated this gene cmSAT. The N-terminal region
      of the cmSAT protein has characteristics of a chloroplast targeting peptide.
      cmSAT protein fused with a 6x histidine tag complemented a SAT deficient
      Escherichia coli mutant. The protein was purified with its SAT activity, which
      was inhibited by cysteine, using the high affinity of the histidine tag in an Ni
      NTA column. The Km values for acetyl-CoA and l-serine were 0.3 and 0.1 mM,
      respectively. Southern blotting indicated the existence of other SAT isoforms in
      C. merolae. A 2.4 kb transcript was always detected when growth was synchronized
      under a 12-h light/dark cycle. Under these conditions, a 31-kDa protein was
      always detected on immunoblots, indicating processing of the cmSAT protein and
      constitutive expression of cmSAT. A 45-kDa protein, thought to be the unprocessed
      cmSAT protein, was detected in the dark period, from M phase to early G1 phase.
      No significant change in the level of protein expression was detected under
      continuous darkness or in a sulfate-deficient medium. Using immunoelectron
      microscopy, the cmSAT protein was primarily detected in the stroma and a few were
      detected in the cytoplasm, which indicate that cmSAT protein is transported to
      and functions in a chloroplast.

PMID- 9622598
TI  - Lipopolysaccharide (LPS)- and muramyl dipeptide (MDP)-induced anorexia during
      refeeding following acute fasting: characterization of brain cytokine and
      neuropeptide systems mRNAs.
AB  - We investigated the effectiveness of lipopolysaccharide (LPS) and muramyl
      dipeptide (MDP) administered into the brain to induce anorexia in acutely fasted
      Wistar rats allowed to refeed. We also assayed for changes in mRNA levels of IL-1
      system components, TNF-alpha, TGF-beta1, glycoprotein 130 (gp 130), leptin
      receptor (OB-R), pro-opiomelanocortin (POMC), neuropeptide Y (NPY),
      glucocorticoid receptor (GR), and CRF receptor (CRF-R) in selected brain regions.
      The data show that LPS and MDP induced anorexia differentially during refeeding.
      LPS-induced anorexia was of a stronger magnitude and duration than that of MDP.
      RNase protection assays showed that LPS and MDP significantly increased the
      expression of IL-1beta, IL-1 receptor type I, and TNF-alpha mRNAs in the
      cerebellum, hippocampus, and hypothalamus; LPS was more potent in all cases. MDP
      treatment, on the other hand, induced a stronger increase in hypothalamic levels
      of IL-1 receptor antagonist (IL-1Ra) and TGF-beta1 mRNAs relative to LPS. In
      addition, competitive RT-PCR analysis showed that LPS induced an eleven-fold
      increase in IL-1alpha mRNA in the hypothalamus relative to vehicle. These
      findings suggest that LPS and MDP mediate anorexia through different cytokine
      mechanisms. A stronger up-regulation of anti-inflammatory cytokines (IL-1Ra and
      TGF-beta1) mRNA expression by MDP may be involved in the weaker MDP-induced
      anorexia relative to LPS. No significant changes were observed in the peptide
      components examined except for an up-regulation in cerebellar gp 130 mRNA and
      down-regulation of hypothalamic GR mRNA expression in response to LPS or MDP.
      This study shows that LPS and MDP induce anorexia in fasted rats allowed to
      refeed, and suggests an important role for endogenous cytokine-cytokine
      interactions.

PMID- 9622599
TI  - In vitro expression of MMP-2 and MMP-9 in glioma cells following exposure to
      inflammatory mediators.
AB  - Progression of glioma is associated with local degenerative processes which are
      attributed to the activity of gelatinases. As glioma cells are candidate for
      secretion of these enzymes, we have studied in vitro the potential of cytokines
      (interleukin-1alpha (IL-1), tumor necrosis factor-alpha (TNFalpha) and
      transforming growth factor-beta (TGFbeta2)) to regulate the expression of
      gelatinase A and B (Gels A and B, respectively) in two glioma cells of human
      (A172) and rat origin (C6). We showed that IL-1 and TNFalpha both induced gene
      expression and protein secretion of Gel B in both cell lines, as revealed by RT
      PCR and gelatin zymography, respectively. In C6 cells, TNFalpha had no effect on
      Gel A constitutive expression while IL-1 increased its production, but only at
      high doses. We have also demonstrated that TGFbeta2 inhibited both IL-1- or
      TNFalpha-induced gene expression and Gel B production in a dose-dependent manner
      but had no effect on Gel A secretion. The effect of TGFbeta2 on Gel B secretion
      was reversed by phorbol myristate acetate (PMA). Taken together, these data
      suggest that IL-1, TNFalpha and TGFbeta2 tightly regulate Gel B secretion in
      glioma cells, an enzyme which is believed to play an important role in the local
      invasion of brain tissue by tumor cells.

PMID- 9622600
TI  - Transient c-fos gene expression in cerebellar development and functional
      stimulation.
AB  - This study examined the temporal appearance of c-fos expression in rat cerebella
      from birth to postnatal day 21 (P21) and following systemic kainic acid
      administration in adults. During development, Fos positive granule cells appeared
      first at P3 in caudal lobules and extended to all folia by P9. These reactive
      cells occurred in clusters throughout the granular layer and reached their
      highest reactivity by P15. In addition, Fos positive basket and stellate cells
      were seen in the molecular layer at this time. A steep decline in Fos protein
      labeling of the cerebellum began by P18 and was barely detectable in adulthood.
      In adult rats, systemic injection of kainic acid induced c-fos expression in
      granule cells and stellate/basket interneurons within 1 h of treatment. Fos
      reactive granule cells appeared in clusters with some forming distinct
      parasagittal bands in caudal folia. One day after unilateral cerebellar
      lesioning, a limited number of reactive cells were found on the lesion margins. A
      combination of lesioning and systemic kainic acid produced a strong, c-fos
      expression throughout the ipsilateral granular layer as well as in Purkinje cell
      nuclei. Contralateral to the lesion, the pattern of granule cell reactivity
      appeared the same but slightly stronger than those with kainate alone. We
      conclude that c-fos gene expression occurs transiently in granule cells during
      postnatal development and can be rapidly re-induced in the adult following
      systemic injection of glutamate agonists. The c-fos expression patterns suggest
      that subpopulations of granule cells are clustered and related to the
      parasagittal compartments of Purkinje cells.

PMID- 9622601
TI  - Organization of inputs to the dorsomedial nucleus of the hypothalamus: a
      reexamination with Fluorogold and PHAL in the rat.
AB  - Possible inputs to the DMH were studied first using the fluorescent retrograde
      tracer Fluorogold, and identified cell groups were then injected with the
      anterograde tracer PHAL to examine the distribution of labeled axons in and
      around the DMH. From this work, we conclude that the majority of inputs to the
      DMH arise in the hypothalamus, although there are a few significant projections
      from the telencephalon and brainstem. With few exceptions, each major nucleus and
      area of the hypothalamus provides inputs to the DMH. Telencephalic inputs arise
      mainly in the ventral subiculum, infralimbic area of the prefrontal cortex,
      lateral septal nucleus, and bed nuclei of the stria terminalis. The majority of
      brainstem inputs arise in the periaqueductal gray, parabrachial nucleus, and
      ventrolateral medulla. In addition, it now seems clear that inputs to the DMH use
      only a few discrete pathways. Descending inputs course through a periventricular
      pathway through the hypothalamic periventricular zone, a medial pathway that
      follows the medial corticohypothalamic tract, and a lateral pathway traveling
      through medial parts of the medial forebrain bundle. Ascending inputs arrive
      through a midbrain periventricular pathway that travels adjacent to the cerebral
      aqueduct in the periaqueductal gray, and through a brainstem lateral pathway that
      travels through central and ventral midbrain tegmental fields and enters the
      hypothalamus, and then the DMH from more lateral parts of the medial forebrain
      bundle. The results are discussed in relation to evidence for involvement of the
      DMH in ingestive behavior, and diurnal and stress-induced corticosterone
      secretion.

PMID- 9622602
TI  - Regulation of phospholipase C-delta by GTP-binding proteins-rhoA as an inhibitory
      modulator.
AB  - The regulation of Phospholipase C (PLC)delta activity remains obscure. These
      studies show that PLCdelta1 activity is significantly enhanced by both guanosine
      thiotriphosphate (GTPgammaS) and Clostridium botulinum exoenzyme C3 (C3) but not
      by aluminium fluoride. C3 ADP ribosylated a 21-kDa protein in the PLCdelta1
      preparation and Western blotting identified rhoA in these samples. RhoA acts as
      an inhibitory modulator of PLCdelta activity.

PMID- 9622603
TI  - Methylcobalamin amplifies melatonin-induced circadian phase shifts by
      facilitation of melatonin synthesis in the rat pineal gland.
AB  - Effects of methylcobalamin (methyl-B12), a putative drug for treating human
      circadian rhythm disorders, on the melatonin-induced circadian phase shifts were
      examined in the rat. An intraperitoneal injection of 1-100 microg/kg melatonin 2
      h before the activity onset time (CT 10) induced phase advances of free-running
      activity rhythms in a dose-dependent manner (ED50=1.3 microg/kg). Injection of
      methyl-B12 (500 microg/kg) prior to melatonin (1 microg/kg) injection induced
      larger phase advances than saline preinjected controls, while the injection of
      methyl-B12 in combination with saline did not induce a phase advance. These
      results indicate amplification of melatonin-induced phase advances by methyl-B12.
      Pinealectomy abolished the phase alternating effect of methyl-B12, suggesting a
      site of action within the pineal gland. In fact, methyl-B12 significantly
      increased the content of melatonin in the pineal collected 2-h after activity
      onset (CT 14). In contrast, no difference in melatonin content was found at CT
      10, indicating that the effect of methyl-B12 may be gated after the activity
      onset time when endogenous melatonin synthesis is known to increase. These
      results suggest that methyl-B12 amplifies melatonin-induced phase advances via an
      increase in melatonin synthesis during the early subjective night at a point
      downstream from the clock regulation.

PMID- 9622604
TI  - Molecular cloning of the chicken melanocortin 2 (ACTH)-receptor gene.
AB  - The chicken melanocortin 2-receptor (MC2-R) gene was isolated. It is found to be
      a single copy gene encoding a 357 amino acid protein, sharing 65.8-68.7% identity
      with mammalian counterparts. The chicken MC2-R mRNA is expressed in the adrenal
      and spleen, suggesting that the receptor mediates both endocrine and
      immunoregulatory functions of ACTH in the chicken. The amino acid sequence of the
      chicken MC2-R is collinear with those of other subtypes of MC-R, whereas all
      cloned mammalian MC2-Rs contain a gap in the third intracellular loop, suggesting
      that mammalian MC2-R molecules have evolved by lacking a part of the domain which
      determines the specificity of signal transduction in G-protein coupled receptors.
      Interestingly, the codon usage differs dramatically between MC1-R and MC2-R in
      the chicken; the GC-contents at the third codon position in MC1-R and MC2-R are
      94.6 and 50.6%, respectively. It may reflect selective constraints on the usage
      of synonymous codons.

PMID- 9622605
TI  - Mannose-specific lectins modulate ligand binding to AMPA-type glutamate
      receptors.
AB  - Binding of [3H]AMPA was increased above control levels in rat brain membranes
      that had been incubated with concanavalin A (Con A) or a lectin from Lens
      culinaris (LC), both of which bind mannose residues. This did not occur with any
      of six lectins with other specificities. The magnitude of the increased binding
      varied from 15% in cortex to 70% in hippocampus and decreased significantly
      between 3 weeks and 6 months of age. Succinylated Con A was without effect and
      neither Con A nor LC increased binding to solubilized AMPA receptors. Increases
      in binding were not obtained in membranes purified from HEK293 cell lines
      expressing homomeric AMPA receptors. This indicates that mannose specific lectins
      may enhance binding by cross-linking AMPA receptors to each other or to proteins
      that are specific to brain. Con A has been reported to reduce glutamate receptor
      desensitization with higher efficacy at kainate than at AMPA receptors; the
      increase in binding reported here appears to be unrelated to such effects because
      (1) it was not affected by drugs that block desensitization and (2) [3H]kainate
      binding was reduced rather than increased by Con A. These observations suggest
      that AMPA receptor kinetic properties not involving desensitization are
      influenced by extracellular interactions between the receptors and other
      transmembrane proteins.

PMID- 9622606
TI  - Cloning and characterization of an endogenous COS-7 cell thromboxane A2 receptor.
AB  - A cDNA for a thromboxane A2 (TXA2) receptor was cloned from an SV40 transformed
      African Green Monkey kidney cell line (COS-7). The sequence is 98% homologous
      with the isoform of the human TXA2 receptor and has agonist and antagonist ligand
      binding characteristics that are not significantly different from the human
      receptor. Stimulation of the COS-7 cells with the TXA2 receptor agonist, ONO
      11113 resulted in a significant increase in cAMP formation that was blocked by a
      receptor antagonist. The results raise the question of the utility of the COS-7
      cell line for studies of cloned and expressed TXA2 receptor signalling
      mechanisms.

PMID- 9622607
TI  - The extracellular matrix molecule, laminin, induces purkinje cell dendritic spine
      proliferation in granule cell depleted cerebellar cultures.
AB  - Granule cells and glia were eliminated or reduced in organotypic cerebellar
      cultures exposed to cytosine arabinoside. Transplantation of such granuloprival
      cultures with glia or exposure to astrocyte conditioned medium in the absence of
      parallel fibers (granule cell axons) resulted in proliferation of Purkinje cell
      dendritic spines. The aim of the present study was to identify specific astrocyte
      secreted factors that induced dendritic spine proliferation. Known astrocyte
      secreted, neurite promoting factors were screened by application to granuloprival
      cultures and assayed for dendritic spine proliferation by electron microscopy. An
      extracellular matrix molecule, laminin, evoked sprouting of Purkinje cell
      dendritic spines. Dendritic spine proliferation was not associated with known
      neurite promoting parts of the laminin molecule, as two laminin-derived peptides
      with identified neurite promoting domains did not induce dendritic spine
      sprouting. The purpose of laminin-induced dendritic spine proliferation may be to
      elaborate postsynaptic membrane, thereby increasing the target area for arriving
      axon terminals during development or regeneration, both of which have been
      associated with the presence of laminin secreting astrocytes.

PMID- 9622608
TI  - Atrial natriuretic peptide modulates alveolar type 2 cell adenylyl and guanylyl
      cyclases and inhibits surfactant secretion.
AB  - Alveolar epithelial type 2 (T2) cells isolated from the lungs of adult rats
      responded to exogenous atrial natriuretic peptide (ANP) by two signalling
      mechanisms. First, ANP induced a dose-dependent reduction of ligand-stimulated
      adenylyl cyclase activity and cAMP accumulation. This effect was inhibited by the
      addition of GDPbetaS or by pretreatment with pertussis toxin (PT), consistent
      with mediation by a Gi protein(s). PT-catalyzed [32P]ADP-ribosylation,
      immunoblots with specific antisera, and Northern blot analysis demonstrated that
      T2 cells contain the G-proteins Gi2 and Gi3 which could transduce this signal.
      ANP also promoted PT-insensitive, dose-dependent accumulation of cGMP, consistent
      with activation of a receptor guanylyl cyclase. Isoproterenol-stimulated
      phosphatidylcholine secretion was markedly attenuated by ANP, and this effect was
      inhibited by PT pretreatment, consistent with mediation by a Gi protein(s). These
      data indicate that in addition to the lung being a major clearance organ for
      circulating ANP, lung parenchymal cells are targets of ANP action.

PMID- 9622609
TI  - The neurobiology of apolipoproteins and their receptors in the CNS and
      Alzheimer's disease.
AB  - The importance of apolipoproteins in the central nervous system became
      increasingly clear with the association in 1993 of the epsilon4 allele of
      apolipoprotein E with familial and sporadic late-onset Alzheimer's disease.
      Apolipoprotein E is a ligand for several receptors, most of which are found to
      some extent in the brain. This review summarizes the various apolipoproteins and
      lipoprotein receptors found in the brain. A growing body of evidence now
      implicates irregular lipoprotein metabolism in several neurodegenerative
      disorders. We then focus on research linking apolipoprotein E and Alzheimer's
      disease, from clinical studies to biochemical models, which may explain some of
      the complex neurobiology of this disorder.

PMID- 9622610
TI  - Striatal glutamate release is important for development of ischemic damage to
      striatal neurons during rat heatstroke.
AB  - This study attempted to ascertain whether heatstroke-induced ischemia is
      associated with augmented striatal glutamate release and can be attenuated by
      NMDA receptor antagonists. Mean arterial pressure (MAP), striatal cerebral blood
      flow (CBF), striatal glutamate release and striatal neuronal damage score were
      assessed in saline-treated rats and in rats treated with NMDA receptor
      antagonists. Heatstroke was induced by exposing the animals to a high ambient
      temperature; the moment at which MAP and CBF began to decrease from their peak
      levels was taken as the onset of heatstroke. During onset of heatstroke, rats
      displayed higher values of colonic temperature, striatal glutamate release and
      striatal neuronal damage score, and lower values of MAP and striatal blood flow
      compared with normothermic control rats. The decreased MAP, the diminished
      striatal blood flow, the augmented striatal glutamate release and the increased
      striatal neuronal damage score during onset of heatstroke were significantly
      attenuated by pretreatment with an NMDA receptor antagonist such as MK-801 or
      ketamine. In addition, the survival time (interval between onset of heatstroke
      and death) of the rats was extended by pretreatment with one of these two NMDA
      receptor antagonists. These results suggest that marked accumulation of glutamate
      in the striatum is important for the development of ischemic damage to striatal
      neurons during the onset of heatstroke.

PMID- 9622611
TI  - Infusion of the dopamine D1 receptor antagonist SCH 23390 into the amygdala
      blocks fear expression in a potentiated startle paradigm.
AB  - Dopamine (DA) D1 receptors are distributed in the nucleus accumbens and the
      amygdala, two regions of the mesocorticolimbic DA system known to be activated by
      aversive environmental stimuli. The objective of the present study was to
      determine the contribution of D1 receptors in these brain regions to the
      expression of a fear-motivated behavior, notably, potentiated startle in rats.
      Injection of the DA D1 receptor antagonist SCH 23390 into the amygdala blocked
      the ability of a conditioned light stimulus previously paired with footshock to
      enhance acoustic startle amplitudes. Bilateral intracerebral administration of
      SCH 23390 into the nucleus accumbens had no effect on fear-potentiated startle.
      The observed opposing effects of amygdaloid DA D1 receptor antagonism on fear
      expression, along with earlier research demonstrating the involvement of ventral
      tegmental area (VTA) DA neurons on fear-potentiated startle, suggest a role for
      mesoamygdaloid activity in conditioned excitatory fear reactions.

PMID- 9622612
TI  - From behavior to development: genes for sexual behavior define the neuronal
      sexual switch in Drosophila.
AB  - The isolation and analysis of Drosophila mutants with altered sexual orientation
      lead to the identification of novel branches in the sex-determination cascade
      which govern the sexually dimorphic development of the nervous system. One such
      example is the fruitless (fru) gene, the mutation of which induces male-to-male
      courtship and malformation of a male-specific muscle, the muscle of Lawrence
      (MOL). Since the MOL is formed in wild-type flies when the innervating nerve is
      male, regardless of the sex of the MOL itself, the primary site of Fru function
      is likely to be the motoneurons controlling the MOL. The fru gene produces
      multiple transcripts including sex-specific ones. A female-specific mRNA from the
      fru locus has a putative Transformer (Tra) binding site in its 5' untranslated
      region, suggesting that fru is a direct target of Tra. The fru transcripts encode
      a set of proteins similar to the BTB (Bric a brac, Tramtrack and Broad-complex)
      Zn finger family of transcription factors. Mutations in the dissatisfaction (dsf)
      gene result in male-to-male courtship and reduced sexual receptivity of females.
      The dsf mutations also give rise to poor curling of the abdomen in males during
      copulation and failure of egg-laying by females. The latter phenotypes are
      ascribable to aberrant innervation of the relevant muscles. A genetic analysis
      reveals that expression of the dsf phenotypes depends on Tra but not on Doublesex
      (Dsx) or Fru, suggesting that dsf represents another target of Tra. Taken
      together, these findings suggest that the sex-determination protein Tra has at
      least three different targets, dsx, fru and dsf, each of which represents the
      first gene in a branch of the sex-determination hierarchy functioning in a
      mutually-exclusive set of neuronal cells in the Drosophila central nervous
      system.

PMID- 9622613
TI  - Functional synapses in synchronized bursting of neocortical neurons in culture.
AB  - Spontaneous electrical activities in pairs of neocortical neurons in culture were
      simultaneously recorded using a whole cell current clamp technique. Synchronous
      bursting activities were observed in all 59 pairs tested. In 52 pairs of neurons
      electrically stimulated, EPSPs were recorded in 20 pairs (39%), among which 3
      pairs (6%) showed bidirectional coupling. The response latency observed was 4.
      05+/-0.61 ms (mean+/-S.E.M.). The synaptic delay was estimated at 1. 5-1.9 ms,
      suggesting the response latency is derived from a polysynaptic connection. The
      burst latency which was defined as the time difference of the onset of bursting
      in each neuron was 5.87+/-0. 47 ms (mean+/-S.E.M.), and was weakly correlated
      with the spatial distance between the neurons (37.5-600 micro(m) apart)
      (Rs=0.362, tied P value=0.0065). No synchronized bursting was observed in bathing
      solution with a low Ca2+ concentration (0.4 mM) or in bathing solution containing
      50 microM D-AP5 and 15 microM CNQX. No dye-coupling between bursting neurons was
      observed on injection of the small molecule dye Lucifer yellow or the neurotracer
      neurobiotin. Disrupting neural connections completely by cutting the cell layer,
      caused disappearance of synchronized bursting with each neuron bursting
      independently. In conclusion, these results are consistent with the hypothesis
      that synchronized bursting in cultured neocortical neurons is attributed to
      connections by way of several synapses rather than by way of gap junctions and/or
      diffusible factors.

PMID- 9622614
TI  - Age-related changes in rodent cortical acetylcholine and cognition: main effects
      of age versus age as an intervening variable.
AB  - Evidence from aged and demented humans has stimulated research on the effects of
      age on the integrity of cortical cholinergic afferents in rodents. However, a
      comprehensive review of the available data does not consistently support the
      hypothesis that normal aging in rodents robustly affects the function of basal
      forebrain cholinergic projections to the cortex. These data indicate the limited
      significance of age as an independent experimental variable in research on age
      related changes in cortical acetylcholine and associated behavioral or cognitive
      functions. Alternatively, recent studies demonstrated that normal aging in
      rodents potently interacts with the consequences of experimental manipulations of
      this system. Thus, aging acts as an intervening variable in experiments designed
      to elucidate age-related changes in the vulnerability and restorative capacity of
      this neuronal system after injury and degenerative processes. Investigations of
      the interactions between the effects of age and the capacity of the cholinergic
      systems to respond to detrimental processes reveal robust consequences of aging
      on cortical acetylcholine and the cognitive functions mediated by this neuronal
      system.

PMID- 9622615
TI  - Evidence for supraspinal nervous control of external anal sphincter motility in
      the cat.
AB  - The aim of this study was to investigate the role of noradrenergic descending
      nervous pathways in external anal sphincter motility. For this purpose, the
      effects of intravenously injected adrenoceptor antagonist and agonist on the
      tonic electrical activity of this sphincter were studied in anesthetized cats.
      The effects of stimulating the region of the locus coeruleus and the effects of
      intravenous, intracerebroventricular and intrathecal injection of the above drugs
      on the electromyographic responses of this muscle to pudendal nerve stimulation
      were also investigated. The tonic sphincteric activity and the reflex response
      triggered by electrically stimulating pudendal afferent nerve fibers were
      inhibited by alpha1-adrenoceptor antagonist nicergoline and enhanced by alpha1
      adrenoceptor agonist phenylephrine. Stimulation of the locus coeruleus area
      either inhibited or enhanced the reflex responses. Intracerebroventricular and
      intrathecal injection of the alpha2-adrenoceptor agonists, morphine and leu
      enkephalin decreased the amplitude of these reflex responses. All the effects of
      opioids were blocked by naloxone and by spinalization performed at the cervical
      and lumbar levels. The direct response elicited by stimulating the sphincteric
      motor axons was not affected either by these drugs or by the brainstem
      stimulation. These results suggests the existence of a pontine neuronal network
      controlling the motility of the external anal sphincter via noradrenergic and
      opioid neurons.

PMID- 9622616
TI  - Pax-3 is necessary but not sufficient for lbx1 expression in myogenic precursor
      cells of the limb.
AB  - In vertebrates all skeletal muscles of trunk and limbs are derived from
      condensations of the paraxial mesoderm, the somites. Limb muscle precursor cells
      migrate during embryogenesis from somites to limb buds where migration stops and
      differentiation occurs. We have characterized lbx1 homeobox genes in chicken and
      mice and found them to be expressed in migrating limb muscle precursor cells in
      both species. Analysis of splotch mutant mice showed that lbx1 and c-met are
      differently affected by the lack of Pax-3. Limb buds of splotch (Pax-3 mutant)
      mice were devoid of lbx1 transcripts, while expression of c-met was still
      detectable at a low level. The presence of c-met-positive cells in splotch mice
      entering the limbs indicates that migration of cells from somites to limbs is not
      entirely dependent on Pax-3. We show that induction of epithelial to mesenchymal
      transition of Pax-3-positive cells by SF/HGF was not sufficient to induce ectopic
      lbx-1 expression at the inter-limb level, while ectopic limb formation was able
      to activate lbx1 expression. We postulate that Pax-3 is necessary for lbx1
      expression in the lateral tips of somites but additional, yet unknown signals
      derived from limb buds are needed to initiate lbx1 expression. The role of limb
      bud-derived signals involved in targeted muscle precursor cell migration, and
      lbx1 activation was further confirmed by analysis of explanted somite/limb bud co
      cultures in collagen gels.

PMID- 9622617
TI  - Growth factor-mediated neural proliferation: target of ethanol toxicity.
AB  - Ethanol exposure during development is teratogenic. The central nervous system
      (CNS) is particularly susceptible to ethanol toxicity. In fact, heavy gestational
      ethanol consumption is one of the leading known causes of mental retardation in
      the Western world. Ethanol exposure disrupts the proliferation of glia and
      neuronal precursors in the developing CNS. Depending upon cell population and
      blood ethanol concentration, ethanol can either inhibit or stimulate cell
      proliferation. Two features of cell proliferation that are affected by ethanol
      exposure are the growth fraction (the proportion of cells that is actively
      cycling) and the cell cycle kinetics, particularly in the length of the G1 phase
      of the cell cycle. Cell proliferation in the developing CNS reflects the action
      of positive (mitogenic growth factors) and negative (anti-proliferative factors)
      regulators. Increasing evidence shows that ethanol interferes with the action of
      growth factors. In vitro systems are a good model to investigate ethanol
      neurotoxicity, since the effects of ethanol on cultured cells parallel the
      effects of ethanol in the developing CNS. The inhibitory effects of ethanol on
      cell proliferation may result from interference with mitogenic growth factors
      (e.g., bFGF, EGF, PDGF, IGF-I). Conversely, the stimulatory effects of ethanol
      may result from the interference with growth inhibiting factors (e.g., TGFbeta1).
      Interestingly, both in vivo and in vitro studies show that proliferating neural
      cells display differential sensitivity to ethanol. This differential sensitivity
      correlates with their response to mitogenic growth factors; that is, cells that
      are actively regulated by mitogenic growth factors are much more susceptible to
      ethanol than cells that are less or unresponsive to such factors. Ethanol
      interference with growth factor action could occur at three levels: ligand
      production, receptor expression, and/or signal transduction. Thus, ethanol
      induced alterations in the developing CNS that characterize fetal alcohol
      syndrome apparently result from alterations in the regulatory action of growth
      factors.

PMID- 9622618
TI  - alpha2A-adrenergic receptors in the rat nucleus locus coeruleus: subcellular
      localization in catecholaminergic dendrites, astrocytes, and presynaptic axon
      terminals.
AB  - To define the anatomic substrates subserving the inhibitory actions of alpha2
      adrenergic receptors (alpha2-ARs) in the locus coeruleus (LC), we used dual-label
      immunoelectron microscopy with antibodies directed against the A-subtype of
      alpha2-AR (alpha2A-AR) and the catecholamine-synthesizing enzyme tyrosine
      hydroxylase (TH). Of the profiles containing peroxidase labeling for alpha2A-AR
      (alpha2A-AR-IR) in the LC (n=735), most were dendrites ( approximately 50%),
      glial processes ( approximately 30%), and axon terminals ( approximately 15%).
      alpha2A-AR-IR was also observed in unmyelinated axons and perikarya. Within
      dendrites, alpha2A-AR-IR was associated with nonsynaptic regions of the plasma
      membrane and subsurface cisternae. Approximately 60% of dendrites with alpha2A-AR
      IR were dually labeled for TH. Fifty percent of the axon terminals contacting
      alpha2A-AR-immunoreactive dendrites formed asymmetric (excitatory) synaptic
      contacts. Axon terminals with alpha2A-AR-IR were not dually labeled for TH and
      generally formed asymmetric synapses with TH-immunoreactive dendrites that
      contained or lacked alpha2A-AR-IR. Astrocytic processes exhibiting alpha2A-AR-IR
      were closely apposed to TH-labeled dendrites. These results extend previous
      ultrastructural observations of alpha2A-ARs in the LC and suggest that the
      inhibitory actions of norepinephrine and epinephrine in this region may be
      mediated by postsynaptic alpha2A-ARs on catecholaminergic dendrites and
      presynaptic alpha2A-ARs on excitatory inputs to catecholaminergic dendrites. In
      addition, the localization of alpha2A-AR-IR in astrocytic processes apposed to TH
      immunoreactive dendrites suggests a role for alpha2A-ARs in functional
      interactions between catecholaminergic dendrites and neighboring astrocytes.

PMID- 9622619
TI  - Xpat, a gene expressed specifically in germ plasm and primordial germ cells of
      Xenopus laevis.
AB  - cDNAs specific to vegetal poles of Xenopus gastrula embryos were used as a probe
      to screen a gastrula vegetal pole cDNA library. One of the novel clones isolated
      had an RNA expression pattern consistent with it being a component of germ plasm
      and it was thus named Xpat (Xenopus primordial germ cell associated transcript).
      The open reading frame encodes a 35 kDa protein with no clear homologies. The RNA
      is localised to the vegetal pole throughout oogenesis and early cleavage. During
      gastrulation cells containing this message move internally and at tailbud stages
      they migrate in an antero-dorsal direction. Xpat mRNA is not detectable once the
      dorsal mesentery forms. We show that the 3'-UTR is required and is sufficient for
      localisation of exogenous RNA to the vegetal pole of oocytes. We propose that
      Xpat UTR-containing transcripts can be localised by the Vg1 or late pathway of
      mRNA localisation during stage III of oogenesis, but endogenous Xpat appears to
      be localised earlier by a mitochondrial cloud mechanism similar to that proposed
      for Xcat-2.

PMID- 9622620
TI  - Low-level lead-induced neurotoxicity in children: an update on central nervous
      system effects.
AB  - The neurotoxicity of low-level long-term exposure to lead has a special relevance
      in children. An extensive database has provided a direct link between low-level
      lead exposure and deficits in the neurobehavioral-cognitive performance evidenced
      in childhood through adolescence. Electrophysiological studies showed that
      neurosensory processing may be affected by lead, with consequent decrease in
      auditory sensitivity and visuomotor performance. Lead disrupts the main
      structural components of the blood-brain barrier by primary injury to astrocytes
      with a secondary damage to the endothelial microvasculature. Within the brain,
      lead-induced damage occurs preferentially in the prefrontal cerebral cortex,
      hippocampus and cerebellum. Some characteristic clinical features of lead
      poisoning may be attributed to this specific anatomical pattern. The cellular,
      intracellular and molecular mechanisms of lead neurotoxicity are numerous, as
      lead impacts many biological activities at different levels of control: at the
      voltage-gated channels and on the first, second and third messenger systems.
      These effects could be related to lead's ability to interfere with the regulatory
      action of calcium in cell functions. Consequently, it may be assumed that lead
      acts as a chemical stressor and causes breakdown of the homeostatic cellular
      mechanisms. This is expressed in both the anatomical site and the
      neurotransmitter systems which are crucial in modulating emotional response,
      memory and learning. There is no threshold below which lead remains without
      effect on the central nervous system; thus, symptoms could simply be a clinical
      reflection of the brain regions preferentially involved. In integrating these
      physiological and clinical data, it may be suggested that the different
      mechanisms of low level lead neurotoxicity have a final common functional
      pathway.

PMID- 9622622
TI  - Unilateral hippocampal ablation at birth causes a reduction in contralateral LTP.
AB  - Subcortical damage in neonates often has more severe consequences than in adults.
      Unilateral electrolytic hippocampal lesions in adult rats typically result in
      transient memory deficits, whereas neonatal lesions cause lasting memory
      impairments. We hypothesized that unilateral lesions made at birth may affect
      synaptic physiology in the contralateral hippocampus. Consequently, the ability
      to sustain long-term potentiation (LTP), a form of synaptic plasticity believed
      to underlie certain forms of memory, was compared between slices from the
      remaining hippocampus of rats lesioned as newborns and as adults. Initial studies
      showed that a train of 10 stimulation bursts patterned after the hippocampal
      theta rhythm produced robust and stable LTP both in slices from controls and rats
      lesioned at birth. However, a theta burst pattern of stimulation closer to
      intrinsic physiology (five burst pairs separated by 30 s each), induced
      significantly less LTP in slices from rats lesioned at birth compared to those
      from controls and rats lesioned as adults. To investigate possible mechanisms
      underlying the deficit, the degree of paired-pulse facilitation (PPF) as well as
      the amount of depolarization occurring between two successive theta bursts were
      analyzed. The lesion did not detectably change PPF characteristics, suggesting
      that presynaptic mechanisms are normal. However, the extent to which a burst
      response was increased by a prior burst was significantly diminished in slices
      from rats lesioned at birth compared to those from controls and rats lesioned as
      adults, indicating that postsynaptic factors involved in the initial triggering
      events of LTP are affected by the lesion. Reduced ability to sustain LTP in the
      remaining hippocampus may contribute to impaired memory function after unilateral
      neonatal hippocampal lesion.

PMID- 9622621
TI  - Gene regulatory functions of Drosophila fish-hook, a high mobility group domain
      Sox protein.
AB  - In this study we investigate the gene regulatory functions of Drosophila Fish
      hook (Fish), a high mobility group (HMG) Sox protein that is essential for
      embryonic segmentation. We show that the Fish HMG domain binds to the vertebrate
      Sox protein consensus DNA binding sites, AACAAT and AACAAAG, and that this
      binding induces an 85 degrees DNA bend. In addition, we use a heterologous yeast
      system to show that the NH2-terminal portion of Fish protein can function as a
      transcriptional activator. Fish directly regulates the expression of the pair
      rule gene, even-skipped (eve), by binding to multiple sites located in downstream
      regulatory regions that direct formation of eve stripes 1, 4, 5, and 6. Fish may
      function along with the Drosophila POU domain proteins Pdm-1 and Pdm-2 to
      regulate eve transcription, as genetic interactions were detected between fish
      and pdm mutants. Finally, we determined that Fish protein is expressed in a
      dynamic pattern throughout embryogenesis, and is present in nuclear and
      cytoplasmic compartments.

PMID- 9622623
TI  - Xanomeline compared to other muscarinic agents on stimulation of phosphoinositide
      hydrolysis in vivo and other cholinomimetic effects.
AB  - Activation of muscarinic m1 receptors which are coupled to the phosphoinositide
      (PI) second messenger transduction system is the initial objective of cholinergic
      replacement therapy in Alzheimer's disease. Thus, we evaluated the ability of the
      selective muscarinic receptor agonist (SMRA) xanomeline to stimulate in vivo
      phosphoinositide (PI) hydrolysis and compared it to a number of direct acting
      muscarinic agonists, two cholinesterase inhibitors and a putative m1
      agonist/muscarinic m2 antagonist. Using a radiometric technique, it was
      determined that administration of xanomeline robustly stimulated in vivo PI
      hydrolysis and the effect was blocked by muscarinic antagonists, demonstrating
      mediation by muscarinic receptors. The non-selective muscarinic agonists
      pilocarpine, oxotremorine, RS-86, S-aceclidine, but not the less active isomer R
      aceclidine, also effectively stimulated PI hydrolysis in mice. Amongst the
      putative m1 agonists, thiopilocarpine, hexylthio-TZTP as well as xanomeline
      effectively stimulated PI hydrolysis, but milameline, WAL 2014, SKB 202026 and PD
      142505 did not significantly alter PI hydrolysis. Furthermore, WAL 2014 and SKB
      202026 inhibited agonist-induced PI stimulation, suggesting that they act as
      antagonists at PI-coupled receptors in vivo. The cholinesterase inhibitors,
      tacrine and physostigmine, and the mixed muscarinic m1 agonist/m2 antagonist LU25
      109 did not activate in vivo PI hydrolysis. Xanomeline, hexylthio-TZTP and
      thiopilocarpine were relatively free of cholinergic side effects, whereas
      milameline, WAL 2014 and SKB 202026 produced non-selective effects. Therefore,
      these data demonstrate that xanomeline selectively activates in vivo PI
      hydrolysis, consistent with activation of biochemical processes involved in
      memory and cognition and xanomeline's beneficial clinical effects on cognition in
      Alzheimers patients.

PMID- 9622624
TI  - Immunohistochemical analyses of fibroblast growth factor receptor-1 in the human
      substantia nigra. Comparison between normal and Parkinson's disease cases.
AB  - The use of neurotrophic growth factors as a means of preventing loss of the
      dopaminergic (DA) neurons in the substantia nigra (SN) is becoming an accepted
      treatment strategy for Parkinson's disease (PD). In earlier studies, we showed
      that there was a selective loss of basic fibroblast growth factor (bFGF)
      immunoreactivity in DA neurons of the SN in PD suggesting that a deficiency of
      bFGF might contribute to cell death. As a preliminary step to assessing the
      potential for using bFGF or its analogs as therapeutic agents, the expression of
      fibroblast growth factor receptor-1 (FGFR-1) in the SN of normal and PD cases was
      investigated immunohistochemically. FGFR-1 immunoreactivity could be detected in
      DA neurons of the SN in young and old neurologically normal cases with an
      apparent decline with age. FGFR-1 immunoreactivity was also detected in many of
      the residual SN neurons in most of the idiopathic PD cases. These results
      indicate that FGFR-1 immunoreactivity, and possibly FGF binding activity, is
      retained in DA neurons in PD.

PMID- 9622625
TI  - Mash2 is expressed in oogenesis and preimplantation development but is not
      required for blastocyst formation.
AB  - The basic helix-loop-helix transcription factor, Mash2, has been shown to be
      necessary for the development of the spongiotrophoblast of the mature
      chorioallantoic placenta of the mouse. Here we show that Mash2 is transcribed
      during oogenesis and expressed throughout preimplantation development, only
      becoming restricted to the diploid trophoblast around the time of implantation.
      This expression raised the possibility that Mash2 has earlier functions in the
      trophoblast lineage that were not detectable in mutant embryos because of the
      persistence of oogenetically derived protein. This was tested by generating
      viable Mash2-/- females by tetraploid rescue of the extraembryonic defect. Mutant
      embryos derived from such females showed no enhanced phenotype over embryos
      produced from heterozygous females, demonstrating unequivocally that neither
      maternal nor zygotic Mash2 is required for early trophoblast development. If
      Mash2 functions in other aspects of trophoblast development, it must act
      cooperatively with other factors.

PMID- 9622626
TI  - Intrinsic and extrinsic connections of the rat central extended amygdala: an in
      vivo electrophysiological study of the central amygdaloid nucleus.
AB  - Anatomical studies have shown that the central amygdaloid nucleus (CeA) is
      reciprocally connected with the lateral bed nucleus of the stria terminalis
      (BSTL), both structures being major components of the central extended amygdala.
      The CeA also receives projections from the insular cortex (InsCx) and the
      paraventricular thalamic nucleus (PVT). Extracellular unit activity was recorded
      from neurons in the lateral CeA (CeL) in urethane anaesthetized rats and their
      responses were studied after electrical stimulation of the BSTL, InsCx and PVT.
      The spontaneous activity of CeL neurons was low (1.69 spikes/s) and 40% of
      recorded cells were silent. The iontophoretic application of the GABAA
      antagonist, bicuculline, increased the firing rate of 20% of neurons. The BSTL
      stimulation induced an antidromic response in 33% of the tested cells.
      Orthodromic responses were obtained from 83% (BSTL stimulation), 70% (InsCx
      stimulation) and 85% (PVT stimulation) of tested cells, some of which responded
      to both BSTL and InsCx or PVT stimulations. Orthodromic responses mostly
      consisted in 1-3 orthodromic spikes followed by an inhibition. During
      iontophoretic application of bicuculline, stimulation induced additional short
      latency orthodromic spikes, even in cells that were previously unresponsive.
      However, the duration of the inhibition was never reduced. These results indicate
      that GABAergic neurotransmission may play a dominant role in both spontaneous and
      evoked electrical activities in the CeL, probably mediated by local circuit cells
      involved in a feed-forward inhibition. This organization, along with the
      reciprocal connections between the CeL and the BSTL, is considered in the context
      of the extended amygdala.

PMID- 9622627
TI  - Pituitary adenylate cyclase activating polypeptide (PACAP) stimulates mitogen
      activated protein kinase (MAPK) in cultured rat astrocytes.
AB  - Astrocytes, a subtype of glial cells, have been demonstrated to have an abundant
      number of receptors for pituitary adenylate cyclase activating polypeptide
      (PACAP), a neuropeptide of the VIP/secretin family which stimulates cAMP
      accumulation 1000 times more potent than VIP in astrocytes. PACAP is reported to
      stimulate the proliferation of astrocytes at low concentrations at which it does
      not yet stimulate the cAMP accumulation. In the present study, we examined the
      effect of PACAP on the activation of mitogen-activated protein kinase (MAPK), one
      of the important intracellular signals for the proliferation, and compared it
      with that of epidermal growth factor (EGF). To investigate the activation of
      MAPK, we focused on ERK2, one of MAPK, in cultured rat astrocytes. The activation
      of ERK2 was determined by immunoblotting and measurement of the activity in terms
      of the phosphorylating activity of immunoprecipitates with MAPK antibody on
      myelin basic protein. One pM of PACAP38 temporarily activated ERK2 at 10 min. In
      contrast, EGF activated ERK2 from 10 min to 60 min continuously. As for the dose
      response effect, PACAP stimulated ERK2 at as low a concentration as 10-14 M and
      peaked at 10-12 M. Thereafter, its activating effect gradually decreased at 10-10
      M and returned to the basal level at 10-8 M, forming a bell-shaped dose
      dependency. Neither an inhibitor of PKA (H89) nor inhibitors of PKC
      (staurosporine and calphostin C) had any effect on the ERK2 activation induced by
      1 pM PACAP38. Dibutyryl cAMP suppressed ERK2 activity in a dose-dependent manner.
      These data clearly demonstrated that PACAP stimulates MAPK in both a PKA- and a
      PKC-independent manner in cultured rat astrocytes.

PMID- 9622628
TI  - Dual functions of the Drosophila eyes absent gene in the eye and embryo.
AB  - In eyes absent (eya) mutants, eye progenitor cells undergo cell death early in
      development. Whereas the phenotype of eya1 is limited to the eye, other mutations
      are lethal. Genetic and molecular analysis reveals that mutations in one region
      of the gene cause embryonic lethality, whereas mutations throughout the gene
      cause defects in eye development. Mosaic analysis indicates that the eya
      requirement is cell autonomous. In eye-specific mutants, expression in the eye
      disc is lacking while embryonic expression is normal. Both the type I and type II
      transcripts are expressed in the developing eye, and expression of either can
      rescue the eye phenotype. These data indicate a specific requirement for eya
      function in eye progenitor cells that is normally fulfilled by both transcripts.

PMID- 9622629
TI  - Spinal opioid mu receptor expression in lumbar spinal cord of rats following
      nerve injury.
AB  - Previous studies in rats have shown that spinal morphine loses potency and
      efficacy to suppress an acute nociceptive stimulus applied to the tail or the paw
      following injury to peripheral nerves by tight ligation of the L5/L6 spinal
      nerves. Additionally, intrathecal (i.th.) morphine is ineffective in suppressing
      tactile allodynia at fully antinociceptive doses in these animals. The molecular
      basis for this loss of morphine potency and efficacy in nerve injury states is
      not known. One possible explanation for this phenomenon is a generalized, multi
      segmental loss of opioid mu (mu) receptors in the dorsal horn of the spinal cord
      after nerve injury. This hypothesis was tested here by determining whether nerve
      injury produces (a) a decrease in mu receptors in the lumbar spinal cord; (b) a
      decrease in the affinity of ligand-receptor interaction, (c) a decrease in the
      fraction of high-affinity state of the mu receptors and (d) a reduced ability of
      morphine to activate G-proteins via mu receptors. Lumbar spinal cord tissues were
      examined 7 days after the nerve injury, a time when stable allodynia was
      observed. At this point, no differences were observed in the receptor density or
      affinity of [3H]DAMGO (mu selective agonist) or [3H]CTAP (mu selective
      antagonist) in the dorsal quadrant of lumbar spinal cord ipsilateral to nerve
      injury. Additionally, no change in morphine's potency and efficacy in activating
      G-proteins was observed. In contrast, staining for mu opioid receptors using mu
      selective antibodies revealed a discrete loss of mu opioid receptors localized
      ipsilateral to the nerve injury and specific for sections taken at the L6 level.
      At these spinal segments, mu opioid receptors were decreased in laminae I and II.
      The data indicate that the loss of mu opioid receptors are highly localized and
      may contribute to the loss of morphine activity involving input at these spinal
      segments (e.g., foot-flick response). On the other hand, the lack of a
      generalized loss of opioid mu receptors across spinal segments makes it unlikely
      that this is the primary cause for the loss of potency and efficacy of mu opioids
      to suppress multi-segmental reflexes, such as the tail-flick response.

PMID- 9622630
TI  - Effects of corticosterone treatment and rehabilitation on the hippocampal
      formation of neonatal and adult rats. An unbiased stereological study.
AB  - Elevations in the plasma levels of glucocorticoids are associated with cognitive
      impairments that have been ascribed to loss of neurons in the hippocampal
      formation. However, recent studies have strongly challenged this view. In order
      to clarify this issue, we have employed for the first time the optical
      fractionator and the Cavalieri principle, two unbiased stereological tools, to
      estimate respectively the total number of neurons and the volumes of the main
      subdivisions of the hippocampal formation of rats submitted to corticosterone
      treatment for different periods, either neonatally or in adulthood. A significant
      reduction in the number of neurons and in the volumes of the layers of the
      dentate gyrus and CA3 hippocampal field was found in rats exposed to
      glucocorticoids in the neonatal period; furthermore, animals treated with
      corticosterone from birth until 180 days of age had also a reduction in the
      volume of the stratum radiatum of the CA1 hippocampal field. Conversely, when the
      exposure occurred only during adulthood, no significant neuronal loss was
      observed, but there were significant reductions in the volume of layers in the
      dentate gyrus and CA3 hippocampal field. To search for signs of structural
      recovery, we incorporated a group of rats submitted to corticosterone treatment
      during the neonatal period in which the hormonal conditions were restored
      thenceforth. In this group we found a significant increase in the volume of the
      molecular layer of the dentate gyrus when compared with rats that were kept under
      corticosteroid treatment. In conclusion, these data provide a sound structural
      basis for the cognitive deficits observed during, and following, exposure to
      increased levels of glucocorticoids.

PMID- 9622631
TI  - In Drosophila, female gonadal cells repress male-specific gene expression in XX
      germ cells.
AB  - In Drosophila, the sex of XX germ cells is determined by somatic signals. Whether
      sex-specific genes, however, are activated or repressed by somatic signals is not
      known. We have used mgm1, a germline-marker which is specifically expressed in
      male germ cells to analyze sex-specific gene expression of embryonic germ cells.
      We found that XX and XY germ cells that do not contact gonadal tissue can express
      mgm1. In contrast, XX germ cells that were associated with female somatic gonadal
      cells never expressed mgm1. Our results suggest that XX germ cells express male
      specific genes, unless these genes are repressed by feminizing short range
      signals produced by the somatic cells of the prospective ovary.

PMID- 9622632
TI  - Neurocalcin immunoreactivity in the rat main olfactory bulb.
AB  - The morphological characteristics and distribution of neurocalcin (NC)
      immunoreactive elements were studied in the rat main olfactory bulb (OB) using a
      polyclonal antibody and the avidin-biotin immunoperoxidase method. NC-positive
      elements were abundant in the glomerular layer (GL), where numerous immunostained
      external tufted cells and periglomerular cells were detected. Other less abundant
      NC-immunolabeled populations included middle and internal tufted cells, Van
      Gehuchten cells, horizontal cells, vertical cells of Cajal, deep short-axon cells
      and granule cells. This study demonstrates the presence of NC immunoreactivity in
      subsets of different neuronal types in the rat main OB. This calcium-binding
      protein has been found in interneurons, and no evidence of immunoreactivity to NC
      is detected in projecting neurons. Despite the large population of labeled
      external tufted cells, most of them belong according to morphological criteria to
      the local circuit group and some others to those with interbulbar and/or
      intrabulbar connections. The identification of neuronal subpopulations expressing
      NC provides a further characterization and shows the existence of biochemical
      differences within morphologically identical neurons. Thus, this marker may be a
      useful tool in unravelling the circuitries of the rodent OB in both normal and
      experimental conditions. The exact physiological function of NC in the olfactory
      system remains unknown. On the basis of similarities to recoverin, it could be
      involved in mechanisms responsible for sensory adaptation. Additionally, its
      calcium-binding abilities may contribute to improve the temporal precision of
      stimuli transmission, or be concerned with general calcium-related events
      occurring in specific interneuronal groups.

PMID- 9622633
TI  - Brain inflammatory response induced by intracerebroventricular infusion of
      lipopolysaccharide: an immunohistochemical study.
AB  - Inflammatory processes may play a critical role in the pathogenesis of the
      degenerative changes associated with Alzheimer's disease (AD). In the present
      study, we used an animal model of brain inflammation in order to study a possible
      mechanism involved in AD. Lipopolysaccharide (LPS) was used to produce global
      microglial reactivity within the brain of young rats. Time-dependent changes in
      the inflammatory reaction and the participation of glial cells after acute
      injection of LPS (50 or 100 microg) into the lateral ventricle or the fourth
      ventricle were compared with the chronic infusion of LPS (0.15, 0.5, 1.5 or 5.0
      microg/h) into the fourth ventricle (14 days). Several immunohistochemical
      markers were used to characterize the microglial response. Acute and chronic
      exposure to LPS induced major histocompatibility complex class II (MHC II)
      antigen expression, detected with OX-6 antibody, in a sub-population of
      microglial cells in defined brain areas. The morphological features and
      distribution of OX-6 positive cells observed in the proximity of the cannula
      track after LPS injection into the lateral ventricle suggested the recruitment of
      monocytes/macrophages from the periphery. The activation of the resident
      microglial cells was delayed and mainly concentrated within the temporal lobe
      regions and the limbic system. Chronic infusion to LPS into the fourth ventricle
      induced a comparable activation of microglial cells. Quantitative analysis of OX
      6 positive cells showed a dose-dependent response to LPS exposure.

PMID- 9622634
TI  - Spatially- and temporally-restricted expression of meltrin alpha (ADAM12) and
      beta (ADAM19) in mouse embryo.
AB  - The cloning of the full-length cDNA encoding meltrin beta (ADAM19), one of the
      metalloprotease-disintegrins expressed in mouse myogenic cells, revealed that the
      meltrin beta gene encodes a membrane protein closely related to meltrin alpha
      (ADAM12) which participates in myotube formation in vitro. To delineate the
      functions of meltrin alpha and beta, we examined the expression patterns of their
      transcripts during embryogenesis. The meltrin alpha gene is activated in
      condensed mesenchymal cells that give rise to skeletal muscle, bones and visceral
      organs. Meltrin beta mRNA, in contrast, is markedly expressed in craniofacial and
      dorsal root ganglia and ventral horns of the spinal cord, where peripheral
      neuronal cell lineages differentiate. Heart, skeletal muscle, intestine and lung
      also express meltrin beta mRNA transiently. Although the meltrin alpha and beta
      transcripts exhibit distinct expression patterns during embryogenesis, both genes
      are mainly activated in mesenchymal cells that are derived from both mesoderm and
      ectoderm.

PMID- 9622635
TI  - Direct regulation of acetylcholine release by N-methyl-D-aspartic acid receptors
      in rat striatum.
AB  - The aziridinium ion of ethylcholine (AF64A), a cholinergic neurotoxin, was
      injected into the right striatum of a rat. The unilateral injection of 10 nmol
      AF64A reduced the activity of choline acetyltransferase (CAT) and the tissue
      content of acetylcholine (ACh) in the striatum. The striatal contents of dopamine
      (DA), norepinephrine (NE), 5-hydroxyindoleacetic acid (5-HIAA) and gamma
      aminobutyric acid (GABA) were unchanged. These results suggest that the
      cholinospecificity in the striatal lesion was induced by the 10 nmol dose of
      AF64A. The number of N-methyl-D-aspartic acid (NMDA) receptors in the striatum
      treated with 10 nmol AF64A was determined by a specific binding assay using
      [3H](+/-)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid ([3H]CPP), a
      selective ligand for NMDA receptors. The number of the NMDA receptors decreased
      significantly in the injected area. On the other hand, in a microdialysis using
      normal rats, the perfusion of 50 microM NMDA into the striatum increased ACh
      release. The perfusion of 100 microM MK801 which is the specific and non
      competitive NMDA receptor antagonist, decreased the basal levels of ACh release
      and blocked NMDA-elicited ACh release. Taken together, the present results
      strongly suggest that a population of NMDA receptors exists on cholinergic
      interneurons within the striatum, and it directly regulates ACh release.

PMID- 9622636
TI  - The expression pattern of endothelin 3 in the avian embryo.
AB  - We investigated the expression pattern of the endothelin 3 gene, of which the
      mutation, as well as mutation of its receptor (endothelin-B receptor), affects
      the development of two neural crest derivatives: enteric nervous system and
      melanocytes. After previous work showing that these neural crest derived cells
      express endothelin-B receptor or its subtype endothelin-B2 receptor in the avian
      embryo, we have demonstrated that endothelin 3 is expressed by the environment of
      enteric nervous system and melanocyte precursors.

PMID- 9622637
TI  - An incomplete cerebral ischemia produced a delayed dysfunction in the rat
      hippocampal system.
AB  - We investigated whether functional changes occur with incomplete cerebral
      ischemia which do not lead to neural cell death. If functional changes are
      recognized, it is necessary to clarify whether they occur immediately after
      ischemia or after a lag of a few days similar to the pathological changes. Long
      term potentiation (LTP) in both the Schaffer collateral-CA1 and the perforant
      path-dentate gyrus synapses in halothane-anesthetized rats were examined 1 day
      and 4 days after 10 min clamping of the bilateral common carotid arteries. LTP
      was substantially attenuated after clamping of the bilateral common carotid
      arteries. In Schaffer-CA1 synapses, the inhibition of LTP was significant on both
      the 1 day and 4 days after-clamping group. In perforant path-dentate gyrus
      synapses, LTP was significantly inhibited on only the 4 days after-clamping
      group. These results suggest that functional damages may occur with incomplete
      ischemia without any histological damages. In the 1 day after-clamping group, LTP
      was reduced, but the changes in LTP differed from the inhibition of the 4 days
      after-clamping group. Therefore, a so-called delayed dysfunction might exist in
      the hippocampal neurons, despite absence of pathological changes.

PMID- 9622638
TI  - Embryonic expression pattern of the murine figf gene, a growth factor belonging
      to platelet-derived growth factor/vascular endothelial growth factor family.
AB  - Morphogenesis, growth and differentiation of tissues and organs require cell
      interactions mediated by signal molecules, their receptors and transcriptional
      control systems. c-fos-induced growth factor (figf) is a new secreted member of
      the platelet-derived growth factor/vascular endothelial growth factor (PDGF/VEGF)
      family with mitogenic activity on fibroblasts. Here we studied figf expression
      during murine embryonic development. figf expression was detected with a dynamic
      pattern in several body structures and organs such as limb buds, acoustic
      ganglion, teeth, heart, anterior pituitary as well as lung and kidney mesenchyme,
      liver, derma, and periosteum of the vertebral column.

PMID- 9622639
TI  - Hypertrophy of basal forebrain neurons and enhanced visuospatial memory in
      perinatally choline-supplemented rats.
AB  - The effects of choline supplementation during two time-frames of early
      development on radial-arm maze performance and the morphology of basal forebrain
      neurons immunoreactive for the P75 neurotrophin receptor (NTR) in male and female
      Sprague-Dawley rats were examined. In the first experiment, rats were
      supplemented with choline chloride from conception until weaning. At 80 days of
      age, subjects were trained once a day on a 12-arm radial maze for 30 days.
      Compared to control littermates, supplemented rats made fewer working and
      reference memory errors; however, the memory enhancing effects of choline
      supplementation were greater in males than females. A morphometric analysis of
      NTR-immunoreactive cell bodies at three levels through the medial septum/diagonal
      band (MS/DBv) of these rats revealed that perinatal choline supplementation
      caused the somata of cells in the MS/DBv to be larger by 8-15%. In a second
      experiment, choline supplementation was restricted to embryonic days 12-17. A
      developmental profile of NTR immunoreactive cell bodies in the MS/DBv of 0-, 8-,
      16-, 30- and 90-day old male and female rats again revealed that cell bodies were
      larger in choline-supplemented rats than controls. As in the behavioral studies,
      the effect of choline supplementation was greater in male than female rats. These
      data are consistent with the hypothesis that supplementation with choline
      chloride during early development leads to an increase in the size of cell bodies
      of NTR-immunoreactive cells in the basal forebrain and that this change may
      contribute to long-term improvement in spatial memory.

PMID- 9622640
TI  - A highly conserved lens transcriptional control element from the Pax-6 gene.
AB  - We have identified a short segment of the mouse Pax-6 gene 5' flanking region
      that is necessary and sufficient for reporter construct expression in components
      of the eye derived from non-neural ectoderm. This transcriptional control element
      has a highly conserved nucleotide sequence over 341 bp and is located
      approximately 3.5 kb upstream of the start-point for transcription from the most
      proximal promoter (PO) of the Pax-6 gene. The level of identity between the human
      and mouse Pax-6 genes in this region is 93%. When combined either with its
      natural promoter or a heterologous minimal promoter, this element directs
      reporter construct expression to a region of surface ectoderm overlying the optic
      cup beginning at E8.5-9.0 (12-14 somites). Subsequently, expression is restricted
      to the lens (primarily the lens epithelium) and the corneal epithelium. This
      element will provide an important tool in future transgenic analyses of lens
      formation and will allow identification of transcription factors with a central
      function in lens development.

PMID- 9622641
TI  - Axonal expression sites of tyrosine hydroxylase, calretinin- and calbindin
      immunoreactivity in striato-pallidal and septal nuclei of the rat brain: a double
      immunolabelling study.
AB  - Besides the dopaminergic afferent projection system, calbindin (CALB)- and
      calretinin (CR)-immunoreactive fibres of intrinsic and extrinsic origin represent
      the most abundant axonal categories in the rat striatal and lateral septal areas.
      The question arises whether or not they may represent separate populations, or
      whether they form subgroups which co-express more than one of these antigens.
      Therefore, the present study is focused on the distribution patterns of the axons
      single-immunolabelled by the catecholaminergic marker tyrosine hydroxylase (TH),
      and on TH-immunoreactive axons displaying also CR- and/or CALB-immunoreactivity
      in double-immunostained sections. Striking differences were found between the
      patch and matrix compartments of the caudate-putamen (CP). Whereas the vast
      majority of TH-immunoreactive fibres in the patches and a patch-associated
      subcallosal layer co-expressed CR but not CALB, fibres mono-labelled by the TH
      immunoreactivity were predominant in the matrix. The matrix-like regions of the
      core of nucleus accumbens (CACC), fundus striati (FS), the striatal cell bridges
      (CB) and the striatal part of olfactory tubercle (OTU) coincided in this respect
      with the matrix in CP. The absence of CR-immunoreactivity was also characteristic
      of the TH-immunoreactive fibres in the patch-like areas of the accumbal core,
      although a high number of separate CR-immunoreactive axons were present. In the
      shell of nucleus accumbens (SACC) which receives a rich catecholaminergic
      innervation, fibres co-expressing either one of the calcium-binding proteins were
      absent. The islands of Calleja (CJI) displaying a strongly TH-immunoreactive
      centre and a periphery of lower staining intensity, showed only a low number of
      TH-immunoreactive fibres co-expressing CR or CALB. The broad shell-like band of
      TH-immunoreactive axons between medial and lateral part of the septum was single
      stained with the TH-immunoreactivity. In contrast, the TH-positive fibres forming
      basket-like arrangements around some neurons in the dorsal lateral septal nucleus
      co-expressed also CR, but not CALB. The results are discussed in view of the
      recent concepts of basal forebrain organization and the cytochemical
      characteristics of mesencephalic dopaminergic nuclei giving rise to the vast
      majority of the striatal and septal TH-immunoreactive fibre supply, in order to
      correlate the known projection patterns with the content of calcium-binding
      proteins in TH-immunolabelled fibres and presumed cells of origin. The TH
      immunoreactive fibres in the striatal patches displaying CR- but not CALB
      immunoreactivity may originate mainly from neurons in the ventral tier of pars
      compacta (SNC) and from the pars reticulata of substantia nigra (SNR) which show
      identical cytochemical properties. Axons in the matrix of CP and the accumbal
      core as well as in the islands of Calleja single-labelled by the TH
      immunoreactivity or additionally containing CALB and CR may originate from
      neurons in the dorsal tier of mesencephalic nuclei like SN, pars compacta and
      ventral tegmental area. CR-containing TH-immunoreactive basket-like axon
      terminations in the dorsal lateral septal nucleus are likely to originate either
      from mesencephalic nuclei or from the supramammillary region.

PMID- 9622642
TI  - Changes in c-Jun but not Bcl-2 family proteins in p53-dependent apoptosis of
      mouse cerebellar granule neurons induced by DNA damaging agent bleomycin.
AB  - Tumor suppressor gene p53 is a critical regulator of the cellular response to DNA
      damage. To examine the function of p53 in postmitotic CNS neurons, we cultured
      cerebellar granule cells from 15-day-old wild type and p53-deficient mice, and
      analyzed changes of protein expression in apoptosis elicited by DNA damage. When
      cerebellar granule cells from wild type mice were treated with bleomycin, a DNA
      strand-break inducing agent, neuronal death occurred. In contrast, cells from p53
      deficient mice were resistant to bleomycin-induced neuronal death. Furthermore,
      cells from p53 heterozygous mice showed an intermediate resistance between wild
      type and p53-deficient mice. These results show that p53 is required for the
      bleomycin-induced cerebellar granule cell death. To examine which proteins are
      involved in this apoptosis, we examined changes in protein levels of the Bcl-2
      family, including Bcl-2, Bcl-X and Bax. The relative amounts of these proteins
      did not change after bleomycin treatment, suggesting that the changes in the
      levels of these Bcl-2 family proteins are not necessary for apoptosis in this
      system. In contrast, the levels of c-Jun protein significantly increased 6 h
      after treatment with bleomycin in wild type but not in p53-deficient cerebellar
      granule cells. These results raise the possibility that c-Jun is required for p53
      dependent neuronal apoptosis induced by bleomycin.

PMID- 9622643
TI  - Active transport properties of porcine choroid plexus cells in culture.
AB  - We have investigated the transport properties of cultured porcine choroid plexus
      cells grown on permeable membranes and in serum-free medium. Withdrawal of serum
      yielded cell cultures with permeabilities low enough to establish and maintain a
      pH-gradient between the two compartments of the filter system and to allow apical
      fluid secretion. This became possible because of ten-fold increased electrical
      resistance of 1700 Omega cm2 in the absence of serum. These plexus epithelial
      cells transported phenol red, fluorescein, riboflavin and penicillin G from the
      apical to the basolateral side. KM values and vmax were determined and come close
      to in vivo values. Competitive inhibition with probenicid showed that the organic
      anion transporter is involved. Riboflavin transport however was not completely
      inhibited and did not respond quantitatively to the stilben derivate SITS that
      blocks the Cl-/HCO3--exchanger. We assume that an additional transport system
      exists for riboflavin. Ascorbic acid and myo-inositol were transported from the
      basolateral to the apical side in vitro which strongly resembles the in vivo
      transport from the blood to the cerebrospinal fluid. Again the experimental in
      vitro KM values come close to the in vivo values. The established epithelial cell
      culture model thus closely mimics the blood-CSF-barrier and may be a useful tool
      to further elucidate transport to and from the brain.

PMID- 9622644
TI  - FK960, a novel potential anti-dementia drug, augments long-term potentiation in
      mossy fiber-CA3 pathway of guinea-pig hippocampal slices.
AB  - Our previous studies have demonstrated that FK960 (FR59960; N-(4-acetyl-1
      piperazinyl)-p-fluorobenzamide monohydrate), a novel antidementia piperazine
      derivative, exerts beneficial effects on memory deficits in various animal models
      of amnesia in rats [M. Yamazaki, N. Matsuoka, N. Maeda, Y. Ohkubo, I. Yamaguchi,
      FK960 N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate ameliorates the
      memory deficits in rats through a novel mechanism of action, J. Pharmacol. Exp.
      Ther., 279 (1996) 1157-1173.] and in rhesus monkeys [N. Matsuoka, T.G. Aigner,
      FK960 [N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate], a novel
      potential antidementia drug, improves visual recognition memory in rhesus
      monkeys: comparison with physostigmine, J. Pharmacol. Exp. Ther., 280 (1997) 1201
      1209]. To clarify the synaptic mechanisms of its antiamnesic action, FK960 was
      investigated for its effects on the development of long-term potentiation (LTP)
      in guinea-pig hippocampal slices. The magnitude of LTP of population spike
      recorded in CA3 pyramidal neurons was significantly augmented by perfusing FK960
      (10-9-10-6 M) for 25 min before and during tetanic stimulation of the mossy
      fibers, whereas the basal amplitude of population spikes before tetanus was
      hardly affected by the drug. The dose-response curve was bell-shaped with a
      maximal augmentation at 10-7 M. Scopolamine (10-6 M) per se had little effect on
      the magnitude of LTP in the mossy fiber-CA3 pathway, but significantly attenuated
      its enhancement by FK960 (10-7 M). In hippocampal slices from animals treated
      with cysteamine (200 mg/kg, s.c.), which was shown to deplete the hippocampal
      somatostatin, FK960 (10-7 M) hardly affected the LTP. These results suggest that
      FK960 enhances the magnitude of LTP in the mossy fiber-CA3 pathway through an
      activation of the cholinergic-somatostatinergic link in the hippocampal
      formation. Furthermore, it can be postulated that the drug regulates the
      cognitive function by modulating directly synaptic plasticity in the hippocampal
      neuronal network.

PMID- 9622645
TI  - Expression of c-jun, junB, c-fos, fra-1 and fra-2 mRNA in the rat brain following
      seizure activity and axotomy.
AB  - The present study has investigated the congruence of mRNA induction and protein
      expression of inducible transcription factors (ITFs). The patterns of c-jun,
      junB, c-fos, fra-1 and fra-2 mRNAs were studied by radioactive and non
      radioactive in situ hybridization in the adult rat brain following kainate
      induced seizure activity and axotomy. In the same animals, the expression of c
      Jun, JunB and c-Fos proteins was compared with the respective mRNA signals. Using
      radioactive labeled probes all investigated mRNAs showed an onset within 1 h
      after systemic kainate application and the maximal levels were generally reached
      after 3 h. Each mRNA displayed a specific temporo-spatial expression pattern.
      Whereas fra-1 and fra-2 were restricted to the hippocampus, c-jun, junB and c-fos
      were additionally induced in the cortex, amygdala and thalamus. The areas with
      maximal labeling were the dentate gyrus and the hippocampal CA1 and CA3
      subfields. The expression patterns between c-jun, junB and c-fos mRNA were
      virtually congruent with the respective protein. Labeling of the junB and fra-2
      probes with digoxigenin yielded similar results. Twenty-four hours, 3 and 10 days
      following transection of the medial forebrain bundle and the mamillo-thalamic
      tract, high levels of c-jun mRNA (either digoxigenin or radioactive labeled
      probes) and protein were seen in the axotomized neurons of the substantia nigra
      pars compacta and mamillary body whereas the other mRNAs studied and the JunB or
      c-Fos proteins could not be detected. These findings demonstrate that mRNAs
      encoding for ITFs are translated into the respective proteins following
      excitotoxic seizures and axotomy, and that the antisera used for
      immunocytochemistry yield specific expression patterns of homologous proteins.

PMID- 9622646
TI  - Role of brain nitric oxide in (+/-)3,4-methylenedioxymethamphetamine (MDMA)
      induced neurotoxicity in rats.
AB  - The role of nitric oxide (NO) in the long-term serotoninergic neurotoxicity
      induced by (+/-)3,4-methylenedioxymethamphetamine (MDMA) in rats was
      investigiated. Pretreatment with Nomega-nitro-L-arginine (L-NOARG) (10 mg kg-1),
      a nitric oxide synthase (NOS) inhibitor, partially protected against long-term
      serotonin (5-HT) depletion induced by MDMA (40 mg kg-1) in frontal cortex and
      parietal cortex, but not in other brain regions examined. Brain NOS activities in
      these two regions were significantly elevated at 6 h after MDMA administration.
      Moreover, L-NOARG pretreatment caused significant inhibition of brain NOS
      activity but did not affect the acute 5-HT and dopamine (DA) changes or the
      hyperthermia induced by MDMA. These results suggest that it is the NOS inhibitory
      properties of L-NOARG, rather than its effects on the acute monoamine changes or
      the hyperthermia induced by MDMA, that are responsible for the prevention of
      neurotoxicity. The regional differences on the protection of L-NOARG and on the
      activation of NOS by MDMA indicate the unequal role that NO may play in MDMA
      induced neurotoxicity in different brain regions.

PMID- 9622647
TI  - Differential effects of serotonin (5-HT) lesions and synthesis blockade on
      neuropeptide-Y immunoreactivity and 5-HT1A, 5-HT1B/1D and 5-HT2A/2C receptor
      binding sites in the rat cerebral cortex.
AB  - The present study was aimed at comparing the effects of serotonin (5-HT)
      synthesis blockade using chronic administration of p-chlorophenylalanine (PCPA)
      and 5,7-dihydroxytryptamine injections of variable volume (3 vs. 6 microl) on the
      density of NPY immunoreactive (Ir) neurons and binding of [3H]8-OH-DPAT, S-CM
      G[125I]TNH2 and [125I]DOI to 5-HT1A, 5-HT1B/1D, and 5-HT2A/2C receptors in rat
      cortical regions. Three weeks after large but partial (89% depletion in 5-HT
      tissue concentration) lesions of 5-HT neurons no changes in neither NPY
      immunoreactivity nor 5-HT receptor binding were detected. The complete 5,7-DHT
      lesions produced increases in the number of NPY-Ir neurons in the upper regions
      of the cingular (134%), frontal (140%) and parietal cortex (48%) and
      corresponding decreases in 5-HT2A/2C binding (16-26%). No changes in 5-HT1A and 5
      HT1B/1D binding were observed after lesions of this kind. After PCPA treatment,
      decreases in NPY-Ir neurons density (22-40%) and increases in 5-HT1A and 5
      HT1B/1D receptor binding sites (20-50%) were distributed in both upper and deeper
      cortical regions. The lack of effect of the partial lesion suggests that spared 5
      HT neurons may exert compensatory mechanisms up to a large extent. The changes in
      NPY immunoreactivity and 5-HT2A/2C binding detected in the upper regions of the
      cortex after complete 5-HT lesions probably result from local cellular
      rearrangements, whereas blocking 5-HT synthesis has more widespread influence on
      NPY neurons and on 5-HT1A and 5-HT1B/1D receptor subtypes. Moreover, decreases in
      DOPAC concentrations detected only after complete lesions suggest that the
      involvement of catecholaminergic transmission may also differentiate 5,7-DHT and
      PCPA treatments. Altogether, these data suggest that different receptor subtypes
      might be involved in 5-HT-NPY relationships.

PMID- 9622648
TI  - Post-hypoxic frequency decline does not depend on alpha2-adrenergic receptors in
      the adult rat.
AB  - The aim of this study was to determine whether post-hypoxic frequency decline
      (PHFD) requires central activation of alpha2-adrenergic receptors. PHFD is
      defined as the undershoot in respiratory frequency that occurs immediately
      following brief hypoxic periods. Adult anesthetized, vagotomized rats were
      exposed to hypoxia (8% O2, mean=45 s) before and after intracerebroventricular
      (i.c.v.) infusion of vehicle or alpha2-antagonist. The efficacy of the i.c.v.
      antagonist was assessed by recording the response to intravenous injection of
      alpha2-agonist before and after the infusion. We compared breathing frequencies
      before, during, and after hypoxia, both before and after treatments. The decline
      in breathing frequency after hypoxia was not prevented by the alpha2-antagonists,
      RX 821002 or SK&F-86466. Guanabenz, an alpha2-agonist, prolonged baseline
      expiration and potentiated PHFD. Prior treatment with SK&F-86466 blocked the
      agonist-evoked response which was also reversed by subsequent administration of
      SK&F-86466. We conclude that PHFD does not require the activation of alpha2
      adrenergic receptors, but that alpha2-adrenergic receptors can modulate resting
      and post-hypoxic respiratory frequency.

PMID- 9622649
TI  - Inhibition of M-type K+ current by linopirdine, a neurotransmitter-release
      enhancer, in NG108-15 neuronal cells and rat cerebral neurons in culture.
AB  - The effect of linopirdine, a neurotransmitter-release enhancer, on the M-type K+
      current, IK(M), was examined in NGPM1-27 cells, mouse neuroblastomaxrat glioma
      NG108-15 cells transformed to express m1-muscarinic acetylcholine (ACh)
      receptors, using the nystatin-perforated patch-recording mode under voltage-clamp
      conditions. The application of linopirdine induced the inward current associated
      with an inhibition of IK(M), which mimics an excitatory part of the ACh-induced
      responses in NGPM1-27 cells. The affinity of linopirdine for the inhibition of
      IK(M) was 24.7 microM in NGPM1-27 cells. In the presence of linopirdine, ACh
      failed to evoke a further inward current, but ACh still elicited an outward
      current, thus suggesting that the Ca2+-dependent K+ current is rather insensitive
      to linopirdine. Linopirdine also inhibited another voltage-gated potassium
      current (IK(V)) at the concentration of 72.3 microM. Finally, the inhibitory
      effect of linopirdine on IK(M) was confirmed in pyramidal neurons acutely
      dissociated from the rat cerebral cortex at 35.8 microM. The results suggest that
      linopirdine is thus considered to be an inhibitor of some type of K+ channels in
      both NGPM1-27 cells and the rat cerebral neurons.

PMID- 9622650
TI  - Gender-specific apposition between vasoactive intestinal peptide-containing axons
      and gonadotrophin-releasing hormone-producing neurons in the rat.
AB  - Light microscopic double labeling immunocytochemistry for vasoactive intestinal
      peptide (VIP) and gonadotrophin-releasing hormone (GnRH) was carried out on the
      hypothalami of male and female rats. It was found that the number of VIP boutons
      that terminate on GnRH neurons and the percentage of GnRH neurons contacted by
      VIP axons were higher in females than in males. This sexual dimorphic interaction
      of VIP fibers and GnRH neurons may indicate the involvement of VIP in the gender
      specific regulation of gonadotrophin release in rats.

PMID- 9622651
TI  - Bilaterally projecting neurons in the two visual pathways of chicks.
AB  - By means of a double-labeling technique, we have investigated the organization of
      the bilateral thalamo-Wulst and tecto-rotundal projections in 2-day old chicks.
      After injecting fluorogold (FG) into one side of the visual Wulst and rhodamine B
      isothiocyanate (RITC) into the other side of the visual Wulst, the labeled
      neurons in the nucleus geniculatus lateralis pars dorsalis (GLd) were examined.
      Although the distribution areas of ipsilaterally and contralaterally labeled
      neurons overlap partly, very few double-labeled neurons were found (only 0.01%
      double-labeled neurons). This suggests that the ipsilateral and contralateral
      projections to the Wulst come from different neuronal populations of the
      thalamus. The FG and RITC were also injected into the rotundal nuclei (Rt) on
      each side of the thalamus and the labeled neurons in the optic tectum (TeO) were
      examined. In the TeO, the distribution areas of the neurons labeled ipsilaterally
      and contralaterally to Rt overlap completely and we found that up to 45% of the
      tectal cells were double-labeled by both FG and RITC. Therefore, many tectal
      neurons have axon collaterals so that they project to the Rt on both sides of the
      thalamus and must send information simultaneously to both sides of the brain. The
      differences in the structural organization of the two visual pathways are
      discussed with reference to the transmission of information to higher centers on
      both sides of the brain.

PMID- 9622652
TI  - c-Fos expression in NMDA receptor-contained neurons in spinal cord in a rat model
      of inflammation: a double immunocytochemical study.
AB  - Double-labeling techniques were used to demonstrate the nociceptive activation of
      NMDA receptor-contained neurons in spinal dorsal horn by using c-Fos
      immunoreactivity as an indicator of this activation in a rat model of
      inflammation. About 25% and 55% of the c-Fos-immunoreactive neurons that were
      found in laminae I-II and lamina V showed NMDA receptor immunoreactivity, while
      about 4% and 11% of NMDA-receptor immunoreactive neurons in these two regions
      showed c-Fos immunoreactivity, respectively. The implication of the results was
      discussed.

PMID- 9622653
TI  - Saccades induced electrically from the dorsomedial frontal cortex: evidence for a
      head-centered representation.
AB  - The amplitude and direction of saccadic eye movements evoked electrically from
      the dorsomedial frontal cortex (DMFC) of monkeys vary with starting eye position.
      This observation has been used to argue that the DMFC codes saccadic eye
      movements in head-centered coordinates. Whether the amplitude and direction of
      the evoked saccades are also affected by changes in head position has never been
      demonstrated. Such a result would argue against a head-centered representation,
      and instead would suggest a representation anchored to another body part. Tests
      were conducted on rhesus monkeys to determine whether changing the position of
      the head with respect to the trunk or changing the position of the head with
      respect to the gravitational axis alters saccadic parameters. The amplitude and
      direction of saccadic eye movements remained invariant to such manipulations.
      These findings confirm the claim that the DMFC encodes saccadic eye movements in
      head-centered coordinates.

PMID- 9622654
TI  - Characterization of [3H]5-hydroxytryptamine and [3H]spiperone binding sites in
      clathrin-coated vesicles from bovine brain.
AB  - Coated vesicles prepared from bovine brain cerebral cortex exhibited [3H]5
      hydroxytryptamine (5-HT, serotonin) and [3H]spiperone binding activities. The
      binding activities were localized in the inner core vesicles. Binding reached an
      equilibrium level by 30-45 min at 30 degreesC, and was reversed by the addition
      of 100 microM 5-HT for [3H]5-HT binding or 10 microM ketanserin for [3H]spiperone
      binding. The saturation binding experiments indicated a single class of binding
      sites for [3H]5-HT and [3H]spiperone with apparent Kd values of 2.4 and 1.75 nM,
      respectively. The binding of [3H]5-HT was displaced by 5-HT and 8-hydroxy-2-(di-n
      propylamino)-tetralin (8-OH-DPAT), but not by ketanserin. The binding of
      [3H]spiperone was displaced by spiperone and ketanserin but not by 5-HT or 8-OH
      DPAT even at 1 mM. The coated vesicles were shown by immunoblotting assay to
      contain alpha-subunits of GTP-binding proteins, Galphas, Galphai2, Galphai3,
      Galphao and Galphaq/11. Forskolin-stimulated adenylate cyclase activity in the
      coated vesicles was inhibited to 80% of the control level by 5-HT or 8-OH-DPAT.
      These results suggested that 5-HT1A and 5-HT2A receptors are present in bovine
      brain coated vesicles and that the 5-HT1A receptors are coupled to adenylate
      cyclase activity via GTP binding proteins.

PMID- 9622655
TI  - Changes in the distribution of nitric oxide synthase immunoreactive nerve fibers
      in the chronically hypoxic rat carotid body.
AB  - The distribution of nitric oxide synthase (NOS) immunoreactive nerve fibers in
      the carotid body was compared between normoxic and chronically hypoxic rats (10%
      O2 and 3.0-4.0% CO2 for 3 months). NOS immunoreactive fibers appeared as thin
      processes with many varicosities. They were distributed predominantly around
      small arteries and arterioles, and around clusters of glomus cells. When
      expressed by the density of varicosities per unit area in the parenchyma, the
      density of NOS fibers associated with the vasculature and with the glomus cells
      in the chronically hypoxic carotid bodies was significantly decreased. Because
      nitric oxide (NO) is an inhibitory neuronal messenger in the normoxic carotid
      body, the present findings suggest that the sensory mechanisms in the hypoxic
      carotid body may be involved in 'disinhibition' resulting from reduced NO
      synthesis.

PMID- 9622656
TI  - Age-related alteration of the adenosine/dopamine balance in the rat striatum.
AB  - An antagonistic interaction between adenosine A2A- and dopamine D2-receptors has
      been described. Radioligand binding experiments showed a predominant reduction in
      the number of D2 vs. A2A-receptors in the striatum of aged compared to young
      rats. The A2A-receptor-mediated antagonistic modulation of D2-receptor binding
      remained unchanged in aged animals. In striatal homogenates a significant
      increase in adenosine and no change in dopamine content was found in aged vs.
      young rats. These results reveal the existence of an age-dependent imbalance of
      adenosine vs. dopamine in favor of adenosine, which involves both presynaptic and
      postsynaptic mechanisms.

PMID- 9622657
TI  - Muscarinic elicitation of EEG asymmetry in freely moving rats.
AB  - Averaged frequency spectra (0.5-30 Hz) of electroencephalogram (EEG) were studied
      in six freely moving rats with chronically implanted electrodes in symmetrical
      areas of somatosensory cortex. Hemispheric asymmetry in spectra of an ongoing EEG
      was expressed as a power decrease in 15.6-17.2 Hz band on the left hemisphere and
      as that in 25.2-27.8 Hz band on the right one. Physostigmine subcutaneous (s.c.)
      injection (0.25 mg/kg) provoked appearance of the significant left brain bias in
      4.7-8.6 Hz range of EEG spectra and the right brain bias in 19.3-21.3 Hz band.
      These physostigmine effects were counteracted by scopolamine (1.5 mg/kg, s.c.)
      injected 30 min before. It is suggested that a muscarinic component may be
      involved in the interhemispheric cooperation associated with cortical theta
      activity in rats.

PMID- 9622658
TI  - Transforming growth factor beta's 1, 2 and 3 inhibit proliferation of ramified
      microglia on an astrocyte monolayer.
AB  - The transforming growth factor beta's (TGFbeta) are a multipotent family of
      cytokines with strong immunosuppressive and neurotrophic effects. In the current
      study, we examined the effect of the TGFbeta's 1, 2 and 3 on the proliferation of
      ramified microglia cultured on top of a confluent astrocyte monolayer. All three
      TGFbeta isoforms inhibited proliferation. PCR analysis also showed the presence
      of mRNA for the TGFbeta receptors type I and II and for all 3 TGFbeta isoforms in
      microglia, astrocytes and in co-cultures. Moreover, removal of this endogenous
      TGFbeta activity with antibodies against TGFbeta1 and TGFbeta3 strongly
      stimulated microglial proliferation. These inhibitory effects on the
      proliferation of ramified microglia suggest that TGFbeta's may play an important
      role in the regulation of the microglial population under normal conditions and
      after injury or disease in the central nervous system.

PMID- 9622659
TI  - Dimethyl sulfoxide, but not acidosis-induced metallothionein mRNA expression in
      neonatal rat primary astrocyte cultures is inhibited by the bioflavonoid,
      quercetin.
AB  - Metallothionein (MT) mRNA levels were analyzed following exposure of neonatal rat
      primary astrocyte cultures to physiologic pH (7.4), acidosis (pH 6.5 and 6.0),
      and dimethyl sulfoxide (DMSO). Treatments were carried out both in the presence
      and absence of the bioflavonoid, quercetin. Total RNA was probed on northern
      blots with [alpha32P]dCTP-labeled synthetic cDNA probes specific for rat MT
      isoform mRNAs. MT-I and MT-II mRNA levels in astrocytes exposed to pH 6.5 or pH
      6.0 were increased compared to controls (pH 7.4). Treatment with DMSO in the
      presence and absence of acidosis, also increased MT-I and MT-II mRNA levels
      compared to controls (pH 7.4). The DMSO-induced increase in MT mRNA expression
      was reversed by treatment of astrocytes with quercetin, such that MT-I and MT-II
      mRNA levels in DMSO plus quercetin-treated astrocytes were indistinguishable from
      mRNA levels in their respective controls at pH 7.4, pH 6.5, and pH 6.0. These
      findings suggest that both acidosis and DMSO exposure are associated with
      increased astrocytic MT synthesis at the mRNA level, and that quercetin,
      effectively blocks MT mRNA induction by DMSO.

PMID- 9622660
TI  - Effects of the GABA agonists baclofen and THIP on long-term compensation in
      hemilabyrinthectomised rats.
AB  - Horizontal eye movements, elicited by sinusoidal rotation in darkness, were
      recorded with a magnetic search coil technique in pigmented rats,
      hemilabyrinthectomised 8-12 weeks before the investigation. Separate gains during
      rotation towards the lesioned side (LS) and the intact side (IS) were calculated
      by a computer program, demonstrating an asymmetry. Systemic single administration
      of the GABAB agonist baclofen caused a dose-related temporary rebalancing of the
      compensatory eye movements to the LS and the IS. At an optimal dose of 14
      micromol/kg b.wt symmetry was achieved by excitation of eye movements during
      rotation to the LS and depression during rotation to the IS. Administration of
      the GABAA agonist THIP did not obviously reduce the asymmetry. It is suggested
      that stimulation of GABAB receptors modifies the tonic imbalance between the
      bilateral vestibular nuclei and/or the central processing of the input from the
      peripheral sensory organs.

PMID- 9622661
TI  - Autoradiographic localisation of substance P (NK1) receptors in human primary
      visual cortex.
AB  - This study utilised autoradiography to examine [125I]-Bolton Hunter substance P
      (BHSP) binding in postmortem human visual cortex. In the primary visual area,
      layers I-III, IVC and VI exhibited low levels of BHSP binding, while high levels
      were observed in layers IVB and V. Because cells in layers IVB and V are known to
      be involved in processing direction-specific stimuli, it is possible that SP
      plays a role in modulating this visual process.

PMID- 9622662
TI  - Three-dimensional spatial relationship of neuropeptides and receptors in the rat
      dorsal vagal complex.
AB  - Retrograde tracing, multi-label fluorescence immunohistochemistry, confocal
      microscopy and three-dimensional (3-D) reconstruction techniques were combined to
      examine the spatial relationship of immunoreactive nerve terminals containing
      either calcitonin gene-related polypeptide (CGRP) or substance P (SP) to
      identified gastric efferent neurons in the dorsal motor nucleus of the vagus
      (DMV) in the brainstem of the rat. The availability of an antibody to the
      receptor for SP (NK-1r) permitted observation of the association between peptide
      and receptor. Although both SP-IR and CGRP-IR nerve fibres came in close spatial
      proximity to identified gastric efferent neurons, few discrete contacts between
      these fibres and the neuronal membrane were observed. In addition, NK-1r-IR was
      localized to the somatic and dendritic membranes of a subpopulation of neurons
      within the DMV, with the majority of receptor labelling not in close spatial
      proximity to SP-IR nerve fibres. The methodology described in this study
      permitted the simultaneous observation of the spatial relationship between
      neuropeptide and an identified neuron (and the corresponding receptor in the case
      of SP) in 3-D, which is something that cannot be achieved using conventional
      microscopic techniques

PMID- 9622663
TI  - NGF prevention of neurotoxicity induced by cisplatin, vincristine and taxol
      depends on toxicity of each drug and NGF treatment schedule: in vitro study of
      adult rat sympathetic ganglion explants.
AB  - The simultaneous administration of nerve growth factor (NGF) has been found to
      prevent experimental neuropathies induced by anti-cancer drugs such as cisplatin,
      vincristine and taxol. However, it is clinically important to know whether NGF is
      beneficial once the neuropathy is already manifest. We established a bioassay
      system to examine the preventive effects of NGF in various treatment schedules.
      NGF significantly prevented the inhibition of neurite outgrowth by vincristine
      and taxol regardless of treatment schedules. The pre-treatment and co-treatment
      schedules were effective against cisplatin, but the post-treatment schedule was
      not. With regard to the neurite and nerve cell population densities, only the
      cisplatin group treated with NGF showed lower values than the control. These
      results indicate that NGF-treatment is effective for the toxic sympathetic nerve
      injury induced by vincristine and taxol regardless of the treatment schedule, but
      is not protective against cisplatin-induced nerve cell injury.

PMID- 9622664
TI  - Intrathecal bicuculline does not increase formalin-induced inflammation.
AB  - Intrathecal (i.t.) administration of the gamma-aminobutyric acid (GABA)A receptor
      antagonist bicuculline enhances pain behaviors in the formalin test. This study
      examined whether bicuculline also increases the peripheral inflammation induced
      by formalin. Subcutaneous injection of 0.25 to 5.0% formalin in the plantar
      surface of one hindpaw of the rat produced a concentration-dependent increase in
      plasma extravasation as measured by the Evans Blue method. Pretreatment with 0.3
      microg i.t. bicuculline neither enhanced nor suppressed formalin-induced plasma
      extravasation. This dose of bicuculline also did not affect plasma extravasation
      induced by injection of 3% kaolin/3% carrageenan in the knee of the rat. These
      data indicate that the enhancement of formalin-induced pain behaviors by i.t.
      bicuculline is not secondary to enhanced peripheral inflammation, but more likely
      reflects enhancement of nociceptive transmission in the spinal cord.

PMID- 9622665
TI  - Different effects of low and high dose cardiotonic steroids on cytosolic calcium
      in spontaneously active hippocampal neurons and in co-cultured glia.
AB  - The Na+ pump is crucial for the regulation of [Na+]i (the intracellular Na+
      concentration) in all cells. Three Na+ pump alpha subunit isoforms, alpha1,
      alpha2 and alpha3, are expressed in rat hippocampal neurons, and alpha1 and
      alpha2 are expressed in glia, but the significance of these isoforms is not
      understood. We exploited the different ouabain affinities of the Na+ pump alpha
      subunit isoforms in rat (alpha1, low ouabain affinity; alpha2 and alpha3, high
      ouabain affinity) to probe their possible physiological roles. Low and
      intermediate doses (1-10 microM) of ouabain and its readily reversible analog,
      dihydroouabain, altered the spontaneous elevations of [Ca2+]i (the intracellular
      Ca2+ concentration) in neurons and induced [Ca2+]i transients in glia. Complete
      inhibition of all Na+ pump isoforms (>/=100 microM ouabain) caused sustained
      increases in global neuronal [Ca2+]i in rat neuronal/glial hippocampal co
      cultures and transient [Ca2+]i increases in surrounding glia. High dose ouabain
      was also associated with increased [Na+]i and [H+]i in neurons and glia. In
      contrast, 1 microM ouabain (a concentration that completely inhibits only alpha2
      and alpha3) was not associated with sustained increases in global neuronal
      [Ca2+]i or the sustained derangements in [Na+]i and [H+]i observed with high dose
      ouabain. Reduction of [K+]o to 1 mM suppressed the spontaneous [Ca2+]i
      oscillations in neurons and induced Ca2+ transients in some glia; removal of
      external K+ induced sustained elevation of neuronal [Ca2+]i. These studies
      indicate that the alpha1 isoform is the 'housekeeper' required for maintenance of
      the global Na+ gradient. As suggested by their restricted plasmalemmal
      distribution, the high ouabain-affinity Na+ pump isoforms may have more specific
      roles in neurons and glia.

PMID- 9622666
TI  - Temporal correlation between adenosine outflow and synaptic potential inhibition
      in rat hippocampal slices during ischemia-like conditions.
AB  - The temporal correlation between adenosine outflow and changes in field
      excitatory post synaptic potentials (fEPSP) occurring during ischemia-like
      conditions was investigated in rat hippocampal slices. Five-minute long ischemia
      like conditions resulted in a 100% depression of fEPSP amplitude, followed by a
      complete recovery after 6-7 min of reperfusion. By reducing the duration of the
      ischemic insult to 2 min, fEPSP was depressed by 50%. During both 5 and 2 min of
      ischemia-like conditions, a significant increase in adenosine outflow was
      detected. During reperfusion, when fEPSP amplitude recovered completely, the
      adenosine level in the extracellular fluid returned to basal values. The strict
      relationship between the increase in adenosine outflow and fEPSP inhibition
      supports the hypothesis that adenosine is largely responsible for the synaptic
      transmission depression during cerebral ischemia.

PMID- 9622667
TI  - Differential effects of intrathecally administered N- and P-type voltage
      sensitive calcium channel blockers upon two models of experimental mononeuropathy
      in the rat.
AB  - We investigated the effects of intrathecally administered N-type and P-type
      voltage-sensitive calcium channel (VSCC) blockers on the level of thermal
      hyperalgesia in two neuropathic pain models: the chronic constriction injury
      (CCI) model and the partial sciatic nerve injury (PSNI) model. N-type, but not P
      type, VSCC blockers attenuated the level of thermal hyperalgesia induced by CCI
      in a dose-dependent manner. In the PSNI model, both N-type and P-type VSCC
      blockers had no effect on thermal hyperalgesia. This suggests that some types of
      neuropathic pain may be treatable with N-type VSCC blockers.

PMID- 9622668
TI  - Motion-sensitive neurons in the chick retina: a study using Fos
      immunohistochemistry.
AB  - Fos immunohistochemistry was used to characterize neurons in the chick retina
      activated by optokinetic and stationary stimuli. Higher percentages of co
      localization of Fos and the alpha5 subunit of the nicotinic acetylcholine
      receptor, and Fos and GABA were observed in retinal neurons after optokinetic
      compared to the stationary stimulation. These results indicate an involvement of
      the cholinergic and GABAergic circuitries in the motion detection by chick
      retinal cells.

PMID- 9622669
TI  - Relationship between magnitude of hypothermia during ischemia and preventive
      effect against post-ischemic DNA fragmentation in the gerbil hippocampus.
AB  - Protective effect of hypothermia against DNA fragmentation in hippocampal CA1
      field after transient forebrain ischemia in gerbils was evaluated by changing the
      magnitude of hypothermia. Inhibition of DNA fragmentation was proportional to the
      magnitude of hypothermia. The result indicates that, in terms of susceptibility
      to ischemia, hippocampal CA1 neurons are sensitive to a relatively small
      decrement of temperature, with temperatures </=35 degreesC being critical for the
      prevention of apoptotic process following transient forebrain ischemia.

PMID- 9622670
TI  - Hydrolysis of the neuropeptide N-acetylaspartylglutamate (NAAG) by cloned human
      glutamate carboxypeptidase II.
AB  - Glutamate carboxypeptidase II may modulate excitatory neurotransmission through
      the catabolism of the neuropeptide N-acetylaspartylglutamate (NAAG) and possibly
      other endogenous peptide substrates. To investigate the molecular properties of
      cloned human GCP II (hGCP II), we analyzed the NAAG-hydrolytic activity conveyed
      by transfection of a full-length hGCP II cDNA into PC3 cells, which do not
      express GCP II endogenously. Membrane fractions from these cells demonstrated
      activity with an apparent Km of 73 nM and Vmax of 35 pmol/(mg protein*min).
      Activity was inhibited by EDTA and stimulated by the addition of CoCl2. Addition
      of GCP II inhibitors beta-NAAG, quisqualic acid and 2
      (phosphonomethyl)pentanedioic acid (PMPA) inhibited hydrolysis of 2.5 nM NAAG
      with IC50s of 201 nM, 155 nM and 98 pM, respectively. In competition experiments
      designed to infer aspects of hGCP II substrate selectivity, NAAG was the most
      potent alpha peptide tested, with an IC50 of 26 nM. Folate derivatives and some
      other gamma-glutamyl peptides showed comparable affinity to that of NAAG, also
      displaying IC50s in the low nM range. Taken together with previous evidence
      demonstrating their presence in GCP II-expressing tissues, these data suggest
      that both NAAG and folates are good candidate substrates for GCP II in vivo.

PMID- 9622671
TI  - High potassium-induced glutamate release in the cochlea: in vivo microdialysis
      study combined with on-line enzyme fluorometric detection of glutamate.
AB  - The time course of changes in perilymphatic glutamate release and their Ca2+
      dependency were studied in the guinea pig cochlea during high K+-evoked
      depolarization. The glutamate concentration was analyzed continuously by an
      enzyme-linked fluorometric assay combined with microdialysis. Two peaks of
      glutamate increase were found in response to perfusion for 10 min. In the absence
      of Ca2+, the first peak was diminished, whereas the inhibition of the second peak
      was minimal.

PMID- 9622672
TI  - Immunocytochemical localization of mu-opioid receptor in primary afferent neurons
      containing substance P or calcitonin gene-related peptide. A light and electron
      microscope study in the rat.
AB  - Co-expression of mu-opioid receptor-like immunoreactivity (MOR-LI) with substance
      P (SP)- or calcitonin gene-related (CGRP)-LI was observed in rat trigeminal and
      dorsal root ganglion neurons. In particular, MOR-LI was found in axon terminals
      with SP- or CGRP-LI in laminae I and II of the medullary and spinal dorsal horns.
      MOR may be implicated in modulation of release of SP and CGRP from primary
      sensory afferents.

PMID- 9622673
TI  - Preventive actions of a synthetic antioxidant in a novel animal model of AIDS
      dementia.
AB  - Accumulating evidence indicates that the mechanism for causing AIDS dementia
      complex (ADC) involves the release of damaging inflammatory-related agents by HIV
      infected microglia in the brain resulting in CNS oxidative damage. One such
      agent, tumor necrosis factor alpha (TNF-alpha) is consistently elevated in the
      brains of ADC patients compared to non-demented HIV patients. To model this
      aspect of ADC in rats, chronic ventricular infusions of TNF-alpha were given and
      found to induce several aspects of ADC, including weight loss, learning/memory
      impairment, enlarged lateral ventricles, and increased apoptosis. Concurrent oral
      treatment with the antioxidant CPI-1189 prevented all of these TNF-alpha induced
      effects. The results support TNF-alpha as a key toxic agent in ADC and provide
      the first in vivo evidence that chronic treatment with a synthetic antioxidant
      may protect HIV-infected patients against ADC. Our findings may also have
      implications in other neurological diseases where brain TNF-alpha levels are
      elevated and inflammation/oxidative stress is suspected to be a contributing
      cause, such as Alzheimer's disease and Parkinson's disease.

PMID- 9622674
TI  - Induction of immediate-early genes c-fos and zif268 in the subnucleus oralis by
      noxious tooth pulp stimulation.
AB  - c-fos and zif268 expression were assessed by immunocytochemistry for c-Fos and
      Zif268 proteins in the sensory trigeminal nuclear complex following noxious
      mechanical stimulation of the mandibular incisor pulp of rats. Marked up
      regulation of both immediate early genes was observed in the subnucleus oralis
      ipsilateral to the stimulation. Cavity preparation of the dentine without
      reaching the pulp did not cause significant up-regulation detectable by
      immunocytochemistry. These results provide evidence that noxious dental signals
      reach the ipsilateral subnucleus oralis and up-regulate the transcription of
      immediate early genes c-fos and zif268.

PMID- 9622675
TI  - Antisense mapping of opioid receptor clones: effects upon 2-deoxy-D-glucose
      induced hyperphagia.
AB  - Antisense oligodeoxynucleotides (AS ODNs) directed against exons 1 and 2 of the
      MOR-1 clone significantly and markedly reduced (81-93%) hyperphagia induced by
      the anti-metabolic glucose analogue, 2-deoxy-d-glucose (2DG) across a 4 h time
      course. AS ODNs directed against exons 3 or 4 of the MOR-1 clone had a more
      limited (1-2 h) duration of action upon 2DG-induced hyperphagia. 2DG-induced
      hyperphagia was significantly reduced by AS ODNs directed against exon 2 (44
      51%), but not exons 1 or 3 of the KOR-1 clone across a 4 h time course. Whereas
      an AS ODN probe directed against the KOR3/ORL-1 clone produced small (36%), but
      significant reductions in 2DG-induced hyperphagia, an AS ODN probe directed
      against the DOR-1 clone was ineffective. These data provide further converging
      evidence for the roles of primarily mu, but also kappa1 and kappa3 opioid
      receptors in mediating the hyperphagic effects of glucoprivation.

PMID- 9622676
TI  - Membranous lamellar cytoplasmic inclusions in histiocytes and mesothelial cells
      of serous fluids. Their relationship to phagocytosis of red blood cells.
AB  - OBJECTIVE: To define the composition of cytoplasmic inclusions forming stacks and
      concentric whorls in histiocytes and mesothelial cells of serous fluids,
      imparting to them a resemblance to Gaucher cells, and to draw conclusions on the
      mechanism of their formation. STUDY DESIGN: Three serous fluids (one pleural and
      two pericardial) containing a fair number of the cells referred to were
      progressively subjected to the following studies: (1) cytochemistry for
      mucopolysaccharides, proteins, phospholipids and hemoglobin; (2)
      immunocytochemistry for immunoglobulins IgA, IgG, IgM and lysozyme; (3)
      transmission electron microscopy (TEM), and (4) scanning electron microscopy
      based energy dispersive X-ray microanalysis (SEM-EDAX). RESULTS: All three
      specimens were blood stained and contained large numbers of histiocytes and
      mesothelial cells, arranged singly and in groups, with abundant cytoplasmic
      inclusions. The inclusions stained strongly positive for phospholipids, weakly
      positive for hemoglobin and negative for all other substances examined by
      cytochemistry and immunocytochemistry. By TEM the inclusions had a concentric
      lamellar membranous structure, reminiscent of myelinosomes or lamellar bodies of
      lipid-forming or -storing cells. There was also phagocytosis by histiocytes and
      mesothelial cells of red blood cells, which were mostly in a degenerated state.
      SEM-EDAX of inclusion-bearing cells showed a modest peak for phosphorus and a
      variable but small peak for iron, which corroborated the cytochemical and TEM
      findings. CONCLUSION: Since there was not metabolic or other systemic disease in
      the patients to account for these cells, we posit that phospholipids derived from
      cell membranes of phagocytized cells, especially red blood cells, provide the
      building blocks for the formation of such inclusions as they enter the metabolic
      pathway of phagocytic cells (mesothelial cells and histiocytes) and appear in
      their lysosomal structures. It is advantageous for cytologists to be familiar
      with significance of such changes and not to mistake them for metabolic or other
      systemic disease.

PMID- 9622677
TI  - Smears in the diagnosis of pituitary adenomas.
AB  - OBJECTIVE: To review the cytomorphologic picture of pituitary adenomas as
      revealed by intraoperative smear preparation and to note features useful in
      differential diagnosis from other sellar tumors. STUDY DESIGN: A total of 46
      pituitary adenomas in which intraoperative smears were available were reviewed.
      All tumors were subsequently examined by paraffin section and
      immunohistochemistry. RESULTS: The important cytologic appearances were
      epithelial cords and sheets with dyscohesive ends, acini and papillary
      formations. Cytoplasmic contents, depending on functional status, were variably
      clear, with vacuolation or eosinophilic bodies and occasional paranuclear bodies.
      Mild cellular pleomorphism and binucleate forms were common. CONCLUSIONS:
      Pituitary adenomas possess distinct cytologic features that are important in
      intraoperative differential diagnoses from normal pituitary tissues, germinomas,
      meningiomas, craniopharyngiomas and oligodendrogliomas.

PMID- 9622678
TI  - Immunoperoxidase staining in the differential diagnosis of parathyroid from
      thyroid origin in fine needle aspirates of suspected parathyroid lesions.
AB  - OBJECTIVE: To determine whether immunoperoxidase staining could be used for
      differential diagnosis of parathyroid from thyroid origin in fine needle
      aspirates of suspected parathyroid lesions. STUDY DESIGN: Immunoperoxidase
      staining of parathyroid hormone and thyroglobulin was performed on aspirated
      smears from 10 patients with parathyroid lesions (6 of 10 patients also
      associated with thyroid lesions) and 10 patients with thyroid lesions. All of
      them had surgical tissue proof of the diagnosis. RESULTS: Aspirated smears of six
      patients with parathyroid lesions had strong to moderate staining for parathyroid
      hormone and negative staining for thyroglobulin. Another four patients with
      parathyroid lesions had equivocal staining for parathyroid hormone and negative
      staining for thyroglobulin. All aspirated smears from the 16 thyroid lesions had
      negative staining for parathyroid hormone and positive staining for
      thyroglobulin. CONCLUSION: Immunoperoxidase staining of parathyroid hormone and
      thyroglobulin, done for each suspected parathyroid lesion, was helpful in the
      differential diagnosis of parathyroid vs. thyroid origin.

PMID- 9622679
TI  - Low grade cervical intraepithelial neoplasia associated with human papillomavirus
      infection. Long-term follow-up.
AB  - OBJECTIVE: To investigate the correlation between the development of low grade
      cervical intraepithelial neoplasia (LCIN) and human papillomavirus (HPV)
      infection in cases with long-term follow-up. STUDY DESIGN: Forty-three cases of
      LCIN were followed for more than five years with cytology, colposcopy and Vira
      Pap. Coexistence of HPV infection was sought using a simplified HPV detection
      kit, the Vira Pap method (Dot Blot hybridization). RESULTS: Regressive disease
      was noted in 21 cases, and persistent and progressive disease was noted in 22
      cases. HPV DNA was negative in 81% (17 of 21) of regressive disease and positive
      in 55% (12 of 22) persistent and progressive disease. LCIN had disappeared in 17
      (63%) of 27 cases negative for HPV DNA and was persistent or progressive in 12
      (75%) of 16 cases positive for HPV DNA. CONCLUSION: The clinical course of LCIN
      correlates well with HPV infection.

PMID- 9622680
TI  - HPV typing by in situ hybridization on cervical cytologic smears with ASCUS.
AB  - OBJECTIVE: To assess the prognostic significance of atypical squamous cells of
      undetermined significance (ASCUS) using an in situ hybridization (ISH) method for
      destined cervical cytologic smears and a cocktail of biotinylated DNA probes for
      human papillomavirus (HPV) 6, 11, 16, 18, 31 and 33. STUDY DESIGN: Two HPV DNA
      probe mixtures were applied to the same smear for the simultaneous detection of
      high-risk HPV types 16, 18, 31 and 33 and low-risk HPV 6 and 11. ISH was carried
      out on 192 smears. Among them, 59 showed koilocytosis, 91 ASCUS and 42 normal
      features. RESULTS: Low-risk HPV types were rarely found and associated mainly
      with koilocytosis (17%). High rates of potentially oncogenic HPV were detected in
      ASCUS (41%) and condyloma (73%). In addition, similar levels of positivity were
      found to be associated with ASCUS when using two probe mixtures specific to high
      risk HPV: one included HPV genotypes 16 and 18 and the other, genotypes 31 and
      33. CONCLUSION: HPV DNA typing by ISH on cervical cytologic smears might improve
      the identification of women at high risk of developing precancerous and cancerous
      cervical lesions.

PMID- 9622681
TI  - Genetic damage in exfoliated cells of the uterine cervix. Association and
      interaction between cigarette smoking and progression to malignant
      transformation?
AB  - OBJECTIVE: To determine, through the micronucleus (MN) test, the cytogenetic
      effects of cigarette smoking on exfoliated cells from the uterine cervix in women
      with normal smears and women with inflammatory atypia, squamous intraepithelial
      lesion (SIL) (cervical intraepithelial neoplasia [CIN] 1-3) and cervical cancer.
      STUDY DESIGN: The study group consisted of 200 women divided into three
      subgroups: group 1 (n = 116), women periodically undergoing cervical cytology and
      residents of Salvador-Bahia; group II (n = 57), women residing in Sao Paulo and
      previously selected because of a possible cytopathologic test positive for such
      conditions as human papillomavirus infections or malignant or premalignant
      cervical lesions (CIN 1-3); group III (n = 27), inmates of the Tatuape Penal
      Institution, Sao Paulo. All the women underwent cytologic and colposcopic
      examination, and biopsies were performed on 68 of them. RESULTS: Considering the
      samples as a whole and using the chi(2) test for rare events, the number of MNs
      in smokers was significantly greater than in nonsmokers. It was also greater in
      women with larger exposure to smoking. The occurrence of MN was significantly
      lower in women with normal smears (smokers and nonsmokers) than in those showing
      any kind of pathologic alteration. In nonsmokers the occurrence of MN was similar
      between those with inflammatory atypia (IA) or low grade (L) SIL (CIN 1) and
      significantly higher in women with more severe lesions or high grade (H) SIL (CIN
      2 and 3). Smokers with LSIL (CIN 1) showed a higher number of MNs than nonsmokers
      with a comparable diagnosis and smokers with IA. No differences were observed
      when compared with smokers with HSIL (CIN 2 and 3). MN occurrence was not
      associated with other risk factors for SIL or cancer development, such as age at
      first coitus, number of sexual partners, multiparity and use of hormonal
      contraceptives. CONCLUSION: These results suggest that the mutagenic effect of
      cigarette smoking occurs in cervical cells and that the progression of SIL is
      associated with increased frequency of chromosomal damage. Moreover, the data
      suggest that cigarette smoking introduces an additional risk to the progression
      of low grade LSIL (CIN 1). MN testing would be helpful in monitoring smokers with
      this kind of lesion.

PMID- 9622683
TI  - Aspiration cytology of tubular adenomas of the breast. An analysis of eight
      cases.
AB  - OBJECTIVE: To analyze fine needle aspirates from tubular adenomas of the breast
      and elucidate cytologic features unique to these tumors. STUDY DESIGN: Fine
      needle aspiration (FNA) cytology smears from eight tubular adenomas were
      reviewed, with special attention given to architectural features and individual
      cell characteristics. Smears were then compared with those from 25 fibroadenomas
      and 2 tubular carcinomas for analyzing the distinguishing features. RESULTS:
      Aspirates from tubular adenomas revealed cells arranged as small, three
      dimensional balls or clusters, tubules of different shapes and less frequently as
      closely approximated acini. Cells were uniform, with pale cytoplasm, which showed
      magenta granules in the Giemsa smears from two tumors. Straight tubules, closely
      approximated acini and intracytoplasmic granules were not seen in aspirates from
      fibroadenomas. The tubules in tubular adenomas always showed myoepithelial cells
      and were more open than the angulated tubules of tubular carcinoma. CONCLUSION:
      Tubular adenomas on FNA cytology specifically show cells arranged as small, three
      dimensional balls, tubules or closely approximated acini. Cells are uniform and
      sometimes show intracytoplasmic granules in Giemsa-stained smears.

PMID- 9622682
TI  - Cytologic diagnosis of signet-ring cell carcinoma of the breast.
AB  - OBJECTIVE: To examine the cytologic features of signet-ring cell carcinoma
      (SRCC), defined as carcinoma dominated by signet-ring cells, of the breast and to
      discuss problems that occur in cytodiagnosis. STUDY DESIGN: Five cases of SRCC of
      the breast were examined cytopathologically. Signet-ring cells were subclassified
      into intracytoplasmic lumina (ICL) type and non-ICL type. ICL type had large ICL
      containing mucin. Non-ICL-type cells had wide, amorphous cytoplasm diffusely
      dispersed with mucin. RESULTS: In cases 1 and 2, fine needle aspiration biopsy
      (FNAB) revealed many signet-ring cells (non-ICL type), suggesting SRCC.
      Histologic diagnoses were ductal SRCC containing many signet-ring cells (non-ICL
      type). In cases 3 and 4, signet-ring cells (ICL type) were found sporadically
      among carcinoma cells without signet-ring features. Signet-ring cells were not
      regarded as the major component of the cells; thus, the cytologic diagnoses were
      lobular carcinoma, not otherwise specified. Pathologic diagnoses were lobular
      SRCC. Signet-ring cells were mostly ICL type. In case 5, most carcinoma cells on
      the smears showed signet-ring features (non-ICL type), suggesting SRCC. The
      histologic diagnosis was lobular SRCC, and signet-ring cells were mostly non-ICL
      type. CONCLUSION: Ductal SRCC yielded more cellular smears as compared with
      lobular SRCC; therefore, cytologic diagnosis was easier in the former.

PMID- 9622684
TI  - Diagnostic concordance of telecytology and conventional cytology for evaluating
      breast aspirates.
AB  - OBJECTIVE: To evaluate the diagnostic concordance between static electronic
      images versus glass slides for breast fine needle aspiration (FNA) cytology.
      STUDY DESIGN: Nine malignant and 12 benign breast FNA cases were imaged using the
      Roche Image Manager, at a resolution of 1,024 x 768 pixels. A cytotechnologist or
      pathology resident selected five to nine representative images per case. Case
      histories and images were assembled into hypertext documents. Two pathologist
      blindly made diagnoses for each case based on the images and the clinical history
      and independently made diagnoses for the glass slides, also evaluating each set
      of images and glass slides for a list of cellular features. RESULTS: The two
      pathologist had concordance rates of 90.5% and 66.7% between their image and
      glass diagnoses. For each pathologist's discordant cases, 100.0% and 85.7%,
      respectively, were due chiefly to suspicious rather than definitive diagnoses.
      CONCLUSION: Evaluation of the electronic images indicated that almost all the
      cellular features were comparable to those viewed though a microscope.

PMID- 9622685
TI  - Fine needle aspiration of mucinous (colloid) breast carcinoma. Nuclear grading
      and mammographic and cytologic findings.
AB  - OBJECTIVE: The clinical, mammographic and low grade cytologic features of
      mucinous carcinoma can make it difficult to diagnose by fine needle aspiration
      (FNA). Fine needle aspirates of mucinous carcinoma were reviewed with the
      mammographic findings to improve the diagnostic criteria and specificity for FNA.
      STUDY DESIGN: All aspirates were reviewed for cytologic criteria and cellularity,
      atypia and single epithelial cells (SEC). A nuclear grade was assigned to each
      aspirate. The mammographic findings were correlated with the FNA diagnoses.
      RESULTS: Forty-five patients with an aspirate and confirmed diagnosis of mucinous
      carcinoma were identified. The clinical impressions were: benign tissue (5),
      fibroadenoma (6) and cancer (32). The initial cytologic diagnoses were:
      adenocarcinoma (32), atypical/suspicious for cancer (11), insufficient (1) and
      negative (1). The cytologic findings showed smears with increased cellularity
      (35/45 cases) and minimal atypia. SEC with eccentrically located nuclei and
      eosinophilic cytoplasm were numerous. The assigned nuclear grade was as follows:
      grade 1, 16 cases; grade 2, 20 cases; and grade 3, 6 cases. Abundant mucin was
      present in Papanicolaou-stained slides in 23 cases; focal mucin was observed in
      14 cases. The mammograms showed a smoothly outlined to lobulated mass with only
      slight irregularities identified. CONCLUSION: Mucinous carcinoma has a cytologic
      pattern that includes increased cellularity, with numerous single cells and
      abundant mucin. Although the mammographic findings may mimic a benign lesion, in
      the most patients a specific diagnosis of mucinous carcinoma can be made by FNA.

PMID- 9622686
TI  - Cytodiagnosis of pilocytic astrocytoma in smear preparations.
AB  - OBJECTIVE: To assess the cytologic features in smear preparations of 23 pilocytic
      astrocytomas. STUDY DESIGN: Examination of 23 smears. RESULTS: In all cases, the
      diagnosis was subsequently confirmed on histologic sections. The smears were
      moderately cellular, with a variably myxoid background. They showed bipolar
      "hair" cells with elongated, coarse cytoplasmic processes; bland, oval nuclei;
      Rosenthal fibers; eosinophilic granular bodies; and hyalinized vessels. Stellate
      cells and bare tumor nuclei were also present. Nuclear pleomorphism, vascular
      proliferation, perivascular pseudorosettes, microcalcification and hemosiderin
      laden macrophages were infrequent features. Mitoses and necrosis were absent. The
      differential diagnosis should include diffuse fibrillary astrocytomas of all
      histologic grades, pleomorphic xanthoastrocytoma, ganglion cell tumor, ependymoma
      and reactive gliosis. CONCLUSION: Correlation of cytologic features with clinical
      and radiologic information allows pilocytic astrocytoma to be distinguished from
      other conditions.

PMID- 9622687
TI  - Evaluation of fine needle capillary sampling in superficial and deep-seated
      lesions. An analysis of 670 cases.
AB  - OBJECTIVE: To study the efficacy and merits of a simplified cytologic technique
      of fine needle capillary (FNC) sampling in 670 cases. STUDY DESIGN: FNC sampling
      was tested on a consecutive series of 600 superficial palpable masses and 70 deep
      seated lesions during the period January 1993-September 1993. Among superficial
      masses, sampling was done on 380 lymph nodes, 88 breast lesions, 56 thyroids, 12
      salivary glands and 64 miscellaneous sites. Fifty-five lung lesions were sampled
      using 8 computed tomography, while 15 abdominal masses were sampled using
      ultrasonography. Cell samples were assessed as diagnostically adequate or
      inadequate. RESULTS: The diagnostic adequacy in lymph node, breast and thyroid
      lesions was 95%, 91.07% and 90.09%, respectively. The diagnostic adequacy for
      deep-seated lesions was 91.42%. CONCLUSION: The procedure gives a better
      perception of tumor consistency and control of the hand. FNC resulted in a high
      yield of good-quality material with retention of cellular architecture. It is
      recommended that the operator become familiar with the macroscopic slide
      appearance of a cellular smear. Doubts persist with respect to fibrotic and
      cystic lesions.

PMID- 9622688
TI  - Ameboflagellates in bronchial asthma.
AB  - OBJECTIVE: To distinguish between the existence of detached ciliary tufts (DCTs)
      and the possibility of protozoa in the sputum of asthma patients. STUDY DESIGN:
      One hundred six samples of sputum obtained from 97 patients hospitalized with
      either asthma or other respiratory diseases were examined blindly. The
      combination of such criteria as movement, absence of basal plate, existence of
      red granules, positivity for ultraviolet light and Heidenhain's iron hematoxylin
      stain (for protozoa) was employed to distinguish between DCTs and true protozoa.
      RESULTS: The presence of ameboflagellates in sputum has a diagnostic accuracy of
      86% in predicting or ruling. out the possibility of acute asthma. CONCLUSION: The
      presence of ameboflagellate forms is closely related to the existence of
      bronchial asthma, and these result reflect some etiopathogenic significance in
      asthma.

PMID- 9622689
TI  - Use of CD34 and factor VIII to diagnose hepatocellular carcinoma on fine needle
      aspirates.
AB  - OBJECTIVE: The immunohistochemical staining patterns characteristic of
      hepatocellular carcinoma (HCC) using CD34 and factor VIII antibodies were
      compared with those of other hepatic lesions to determine if these stainings can
      be used as a diagnostic criterion. STUDY DESIGN: We reviewed 44 fine needle
      aspirates from the liver to evaluate the immunoperoxidase staining patterns on
      cell block preparations using CD34 and factor VIII and to determine whether this
      could distinguish HCC from the other lesions. These included HCC (14 cases),
      metastatic tumor (14 cases) and nonneoplastic liver lesions (16 cases). RESULTS:
      This retrospective study showed that in the nine documented cases of HCC,
      staining for CD34 and/or factor VIII was positive. The pattern of staining was
      either peripheral, around small clusters of tumor cells, or linear, diffuse and
      sinusoidal. In all the documented cases (27) of metastatic carcinoma and
      nonneoplastic lesions staining for CD34 and factor VIII was negative. In
      addition, there were eight problematic cases. In 7 cases the cytologic diagnosis
      on Papanicolaou-stained smears was inconclusive about HCC or metastatic
      carcinoma. CD34 and factor VIII confirmed the final diagnosis on the cell blocks.
      Based on this staining, 4 were HCC, 2 were metastatic carcinoma and 1 was
      equivocal, most probably HCC. In one case the differential diagnosis between well
      differentiated HCC and a nonneoplastic liver lesion could not be made on
      cytologic smears, and here, also, CD34 and factor VIII aided in the correct
      diagnosis of a nonneoplastic liver lesion. CONCLUSION: We suggest
      immunoperoxidase staining with CD34 and factor VIII be performed on the cell
      block sections from FNAs in any problematic hepatic case.

PMID- 9622690
TI  - CT-guided fine needle aspiration and needle core biopsy of skeletal lesions.
      Complementary diagnostic techniques.
AB  - OBJECTIVE: To compare the diagnostic sensitivity and specificity of fine needle
      aspiration (FNA) to those of needle core biopsy (NCB) and to attempt to determine
      if a complementary role exists for the two modalities. STUDY DESIGN: Skeletal
      lesions in 144 patients were evaluated with concomitant FNA and NCB over a 21
      year period. FNAs and NCBs were divided as diagnostic of neoplasm, normal or
      inflammatory (i.e., osteomyelitis), or unsatisfactory. The results of each
      modality were then reviewed and compared. RESULTS: In the 144 total cases, a
      diagnosis was possible in 79% (114) cases. FNA and NCB concurred in 73% (83) of
      diagnostic cases. Concurrence was 87% between diagnostic FNA (83) and NCB (95).
      The two modalities agreed in 78% of cases diagnosed as metastatic carcinoma and
      in 59% of primary malignant tumors of bone (17) (excluding Ewing's sarcoma). FNA
      alone was diagnostic in 8% (9) of cases, including 5 metastatic carcinomas, 2
      chondrosarcomas, 1 Ewing's sarcoma and 1 case of osteomyelitis. This represented
      24% of the 38 cases in which NCB was unsatisfactory (11) or normal (27). NCB
      alone was diagnostic in 19% (22) of cases, including 11 metastatic carcinomas, 3
      osteosarcomas, 1 chondrosarcoma, 1 spindle cell sarcoma (not otherwise
      specified), 1 Ewing's sarcoma, 2 capillary hemangiomas and 3 cases of
      osteomyelitis. This represented 43% of the 51 cases in which FNA was
      misinterpreted (2), unsatisfactory (33) or normal (16). NCB more specifically
      typed a metastatic lesion or suggested a primary focus in 21% (12) of the 58
      cases in agreement. It also more specifically subtyped 50% (5) of the 10 primary
      malignant tumors of bone. CONCLUSION: Given these findings, NCB is more specific
      in the evaluation, grading and typing of skeletal lesions in particular malignant
      primary bone tumors. Overall, there is excellent agreement between FNA and NCB,
      especially in the evaluation of benign primary bone tumors. Most important, FNA
      improved the diagnostic yield in 24% of cases when NCB was normal or
      unsatisfactory, obviating the need for rebiopsy. FNA should be performed
      concurrently with NCB in the evaluation of skeletal lesions since the two
      modalities are complementary.

PMID- 9622691
TI  - Compact cell blocks. Use for body fluids, fine needle aspirations and endometrial
      brush biopsies.
AB  - OBJECTIVE: To obtain an ideal cell block wherein the maximal number of cells are
      displayed within the smallest area on the block surface. STUDY DESIGN: Cyto-Rich
      Red (AutoCyte, Inc., Elon College, North Carolina, U.S.A.) is added to fresh
      cellular sediment in a centrifuge tube at a ratio of 1:1. After two minutes,
      three to four drops of plasma and topical thrombin (5,000 U/10 mL) is added. The
      tube is then gently agitated for two minutes, until a gelatinous clot is
      obtained. The clot is then slid onto a lens tissue on top of paper towels. The
      lens tissue is folded once over the clot. By gently squeezing the excess fluid
      from it through the lens tissue into the paper towels, the clot is transformed
      into a flat, compact, densely cellular aggregate, which is painted with
      mercurochrome prior to fixation in formaldehyde. RESULTS: From each of the 495
      cases, including 250 body cavity fluids, 170 fine needle aspirates and 75
      endometrial brush biopsies, processed with the above protocol, there was a
      compact cell block containing packed cells or tissue fragments in a clean
      background devoid of red blood cells. CONCLUSION: The compact cell block is about
      10-20% the size of a conventional cell block, yet more cells are on display, thus
      reducing the need for deeper cuts and screening time while increasing the
      efficiency of cytodiagnosis. The compact cell block technique is particularly
      helpful for endometrial brush biopsies.

PMID- 9622692
TI  - Preparation of heat-labile antigens on air-dried cytologic specimens for
      immunocytochemical analysis.
AB  - OBJECTIVE: To demonstrate the efficacy of Zamboni's solution and storage medium
      for immunocytochemistry of Ki-67, p53 tumor suppressor gene product and CD3 on
      long-preserved, air-dried cytologic specimens. STUDY DESIGN: Air-dried imprint
      cytologic specimens obtained from 13 lymphatic tissues and 13 colorectal cancers
      were fixed with Zamboni's solution and stored for various periods in storage
      medium including 50% glycerol at -10 to -20 degree C. Mouse monoclonal antibody
      PC, PAb 1801 and anti-Leu-4 were used for immunostaining. RESULTS:
      Immunocytochemical identification of Ki-67, p53 and CD3 was possible on specimens
      stored for 36, 32 and 16 weeks, respectively. CONCLUSION: Our method, using
      Zamboni's solution and storage medium, is feasible for immunocytochemistry on
      long-preserved, air-dried cytologic specimens using the three antibodies were
      employed.

PMID- 9622693
TI  - Cytologic features of granulomatous mastitis. Report of a case with fine needle
      aspiration cytology and immunocytochemical findings.
AB  - BACKGROUND: Granulomatous mastitis, a rare condition of unknown etiology, affects
      women of childbearing age and clinically simulates breast carcinoma. CASE:
      Granulomatous mastitis of the breast in a 32-year-old female was studied by fine
      needle aspiration cytology. Aspirated material was quite cellular and consisted
      of epithelioid histiocytes, lymphocytes, plasma cells, neutrophils and
      multinucleated Langhans-type giant cells. However, no cheesy, necrotic material
      in the background was noted. CONCLUSION: Granulomatous mastitis, although
      infrequently reported, appears to have rather characteristic cellular features
      that may allow its recognition.

PMID- 9622694
TI  - Fine needle aspiration cytology presentation of a cellular variant of breast
      myofibroblastoma. Report of a case with immunohistochemical studies.
AB  - BACKGROUND: Myofibroblastoma is a benign stromal tumor of the breast that occurs
      mainly in males. There are few reports on the cytologic aspects of breast
      myofibroblastoma, all of them corresponding to the classic type. Recently, some
      variants of myofibroblastoma were histologically described as: collagenized,
      epithelioid, cellular and infiltrant. Presently, the variant forms of
      myofibroblastoma have not been well characterized pathologically or clinically.
      CASE: A case of a cellular variant of myofibroblastoma was diagnosed by fine
      needle aspiration in a 68-year-old male. The aspirates consisted of highly
      cellular, cohesive groups of randomly arranged, plump oval and spindle cells. The
      nuclei had fine, uniformly distributed chromatin with inconspicuous nucleoli, and
      mild pleomorphism was observed. The cytoplasm was scant, with ill-defined
      borders. We did not observe epithelial components, inflammatory cells or
      collagenous stroma. Histologic examination showed a dense proliferation of
      interlacing, spindle-shaped neoplastic cells, with some nuclear atypia.
      Conspicuous collagen bands were present only focally in the tumor. The margins of
      the specimen were free, but the tumor had infiltrative borders microscopically.
      The spindle cells showed immunoreactivity for vimentin, desmin, muscle-specific
      action and CD 34. CONCLUSION: Our case of a cellular variant of myofibroblastoma
      of the breast with expression of CD 34 adds more one benign spindle cell lesion
      of the breast that should be considered among the diagnostic possibilities for
      aspirates from this group of lesions.

PMID- 9622696
TI  - Subacute measles encephalitis with AIDS diagnosed by fine needle aspiration
      biopsy. A case report.
AB  - BACKGROUND: Subacute measles encephalitis (SME), or measles inclusion body
      encephalitis (MIBE), is a rare central nervous system (CNS) complication
      following infection by the measles (rubeola) virus. It usually occurs in young
      patients with defective cellular immunity from either congenital or acquired
      causes. In the United States, with the resurgence of measles infection and the
      human immunodeficiency virus (HIV) pandemic, subacute measles encephalitis should
      be added to the differential diagnosis in acquired immune deficiency syndrome
      (AIDS) patients presenting with unexplained CNS manifestations. CASE: A 2-year
      old, HIV-positive, white male was admitted for generalized convulsive seizures.
      Vaccination was described as "up to date." Despite treatment with anticonvulsive
      drugs, the child continued to develop frequent partial and generalized seizures.
      Cephalic computed tomography and magnetic resonance imaging revealed a hypodense
      area in the right parietotemporal cortex without an associated mass effect. Fine
      needle aspiration biopsy (FNAB) of the affected area showed neuronal reduction,
      degeneration with eosinophilic intranuclear inclusions, perivascular
      lymphoplasmacytic infiltration and gliosis. Electron microscopy of the
      intranuclear inclusions revealed fine, fibrillar, tubular nucleocapsids,
      consistent with the measles virus. CONCLUSION: Acute measles encephalitis (AME),
      subacute sclerosing panencephalitis (SSPE), and SME are the three CNS syndromes
      associated with measles infection. Serum and cerebrospinal fluid (CSF) antibody
      titres against measles virus are usually high and helpful in the diagnosis of AME
      and SSPE. In SME, neither serum nor CSF antibody titres against measles are high.
      Therefore, FNAB is necessary for a definitive diagnosis.

PMID- 9622695
TI  - Fine needle aspiration cytology of a solid papillary carcinoma of the breast. A
      case report with immunohistochemical studies.
AB  - BACKGROUND: Solid papillary carcinoma of the breast was recently described. This
      tumor display distinctive clinical and morphologic features. It is an intraductal
      papillary carcinoma frequently associated with mucinous carcinoma and
      infiltrating ductal carcinoma not otherwise specified. CASE: Fine needle
      aspiration cytology (FNAC) of a solid papillary carcinoma of the right breast in
      an 82-year-old female, demonstrated a cellular specimen of discohesive, small,
      uniform and ovoid tumor cells, with occasional loose cluster. The cytoplasm was
      abundant and finely granular. The nuclei were round, without marked atypia. The
      nucleoli were inconspicuous. SCant mucinous material was present. The diagnosis
      was confirmed histologically and immunohistochemically. CONCLUSION: The cytologic
      aspects of solid papillary carcinoma of the breast suggest a carcinoma with
      endocrine differentiation and a weak mucinous component.

PMID- 9622697
TI  - Invasive lobular carcinoma of the breast with osteoclastlike giant cells. A case
      report.
AB  - BACKGROUND: Cytologic descriptions of invasive lobular carcinoma of the breast
      with osteoclastlike giant cells (OGCs) are exceedingly rare. Clinically, breast
      carcinoma with OGCs can be confused with fibroadenoma. The histogenesis of OGCs
      has been the subject of debate. CASE: A 48-year-old female presented with a 1.5
      cm, well-demarcated, firm, non-tender, mass involving the right breast. Fine
      needle aspiration biopsy (FNAB) showed the characteristic combination of
      relatively small, uniform carcinoma cells containing conspicuous intracytoplasmic
      lumina and numerous reactive multinucleated giant cells. OGCs were reactive for
      KP-1 and not stained with MIB-1. CONCLUSION: The cytologic appearance of invasive
      lobular carcinoma with OGCs is characteristic. FNAB permits diagnosis of this
      rare type of breast carcinoma. Our study supported a histiocytic nature of the
      OGCs. OGCs were considered not actively proliferated cells.

PMID- 9622698
TI  - Breast carcinoma in situ in a male. Report of a case diagnosed by nipple
      discharge cytology.
AB  - BACKGROUND: Cytologic evaluation of abnormal nipple secretion is a well
      established method for the rapid diagnosis of breast carcinoma in females.
      However, less attention has been focused on male patients presenting with nipple
      discharge. CASE: A case of intraductal carcinoma of the male breast was diagnosed
      by nipple discharge cytology alone. CONCLUSION: This report illustrates the
      usefulness of nipple discharge cytology in the diagnosis of early breast
      carcinoma in males.

PMID- 9622699
TI  - Cytodiagnosis of placental site trophoblastic tumor. A report of two cases.
AB  - BACKGROUND: Placental site trophoblastic tumor (PSTT) is a rare form of
      trophoblastic neoplasm. Approximately 100 cases of PSTT have been reported, but
      we found no report on its cytodiagnosis. CASES: Case 1, a 39-year-old female,
      came to the hospital because of abnormal genital bleeding. Case 2, a 36-year-old
      female came because of amenorrhea for a year. In both cases, endometrial smear
      and intrauterine curettage suggested trophoblastic disease, and hysterectomy was
      performed. Laboratory data revealed a mild increase in human chorionic
      gonadotropin (hCG) and beta-hCG but normal human placental lactogen (hPL). In the
      cytologic examination, the background contained some hemorrhagic and fibrinous
      areas but no necrosis. Most tumor cells stained light green, were round or
      polygonal, and contained abundant cytoplasm. Some were palely stained and had
      vacuoles. Some cells showed hyperchromatism, an irregular nucleus, fine-to-coarse
      chromatin granules and markedly different sizes. Most of the cells were hPL
      positive, and a few were hCG positive. CONCLUSION: Both cases were considered
      benign because of rare mitoses despite cellular pleomorphism. However, careful
      follow-up is required. The differential diagnosis of PSTT is difficult from
      cytologic and biopsy specimens alone but may be achieved with additional magnetic
      resonance imaging findings and positive staining of hPL and hCG.

PMID- 9622700
TI  - Collagenous crystalloids in a fine needle aspirate of a pleomorphic adenoma of
      the minor salivary gland. A case report.
AB  - BACKGROUND: Collagenous crystalloids were previously observed in histologic
      sections of pleomorphic adenoma. However, to the best of our knowledge, there
      have been no English-language reports dealing with collagenous crystalloids in
      fine needle aspirates. CASE: A fine needle aspiration specimen obtained from a
      mass in the hard palate of a 52-year-old female revealed collagenous
      crystalloids. The crystalloids were yellow to green, measured 30-50 microns in
      diameter and were radially arranged. CONCLUSION: This case indicates that
      collagenous crystalloids in salivary gland aspirates may be a clue to the
      diagnosis of pleomorphic adenoma.

PMID- 9622701
TI  - Fine needle aspiration of osteogenic sarcoma metastatic to the lung. A report of
      four cases.
AB  - BACKGROUND: Osteogenic sarcoma (OGS) is a relatively rare, highly malignant
      neoplasm of bone with a tendency to metastasize to the lung. Resection of
      pulmonary metastases in selected instances can increase survival and likelihood
      of a cure. To date, fine needle aspiration (FNA) of OGS had been well
      characterized in primary sites of bone and soft tissue. CASES: Four patients with
      a history of OGS presented with lung nodules suspected to be metastatic disease.
      All were evaluated initially by radiographically assisted FNA. In all cases FNA
      showed spindled or osteoblastlike cells. Two cases demonstrated stromal elements:
      chondroid or osteoid matrix in one case each of chondroblastic and conventional
      OGS. All four cases had histologic confirmation of metastatic OGS in the form of
      subsequent surgical resection of the lung nodules. CONCLUSION: New pulmonary
      nodules in a patient with known malignancy is almost always metastatic disease.
      In a patient with a history of OGS, the diagnosis is extremely likely to be
      metastatic OGS, but a few other entities may occur. Although these entities are
      rare, their occasional occurrence could argue for preoperative confirmation of
      the lung lesion as malignant prior to subjecting the patient to pulmonary
      resection. Our findings show FNA features of OGS that have been previously
      observed in primary sites. These findings are specific enough to diagnose
      metastases if the patient has known primary OGS.

PMID- 9622702
TI  - Sarcomatous hepatocellular carcinoma with malignant ascites. A report of two
      cases.
AB  - BACKGROUND: Although some cases of hepatocellular carcinoma (HCC) are known to
      possess a sarcomatous appearance, their cytologic characteristics in ascites have
      not been reported. CASES: Two Japanese males, aged 67 and 60 were admitted to the
      Gifu Municipal Hospital because of liver tumors. In the first case, although
      transcatheter arterial embolization (TAE) was performed, ascites with neoplastic
      cells continued to enlarge, and the patient died of liver failure. In the second
      case, although TAE, percutaneous ethanol injection therapy, chemotherapy and
      radiotherapy were performed, the patient died of tumor progression: expansion of
      the hepatic tumor, metastases to distal organs and increasing malignant ascites.
      Neoplastic cells in the ascites of both cases had nuclei that were shaped
      irregularly or were vesicular and contained conspicuous nucleoli. A number of
      multinucleated giant cells were also seen. Immunocytochemically, numerous
      neoplastic cells were positive for alpha-fetoprotein. These findings suggested
      sarcomatous HCC. Also, histologic findings of the liver tumors at autopsy showed
      the appearance of sarcomatous HCC. CONCLUSION: In both cases presented, HCC cells
      with sarcomatous change were observed in ascites. To our knowledge, this is the
      first report describing the cytologic diagnosis of sarcomatous HCC in ascites.

PMID- 9622703
TI  - Appearance of primary endometrial and ovarian clear cell adenocarcinoma 17 months
      postpartum. A case report.
AB  - BACKGROUND: Rare cases of endometrial cancer have been reported within two years
      postpartum. However, clear cell adenocarcinoma of the endometrium does not appear
      to have been reported before as occurring in the early postpartum period. CASE: A
      33-year-old-female experienced abnormal uterine bleeding 17 months after the
      delivery of her second child by cesarean section. Computed tomography indicated
      the presence of tumors in the uterus and cul-de-sac. Preoperative evaluation of
      endometrial cytology revealed adenocarcinoma cells. These cells demonstrated a
      centrally located nucleus and translucent, clear cytoplasm, with the so-called
      mirror ball pattern of cell clusters. The cytologic diagnosis was clear cell
      adenocarcinoma. Postoperative histologic evaluation verified the presence of a
      solid type of clear cell adenocarcinoma. The patient was considered to have
      simultaneous primary clear cell adenocarcinoma of the endometrium and ovary.
      CONCLUSION: Preoperative endometrial cytology correctly suggested the histologic
      type of cancer.

PMID- 9622704
TI  - Fine needle aspiration diagnosis of pilomatrixoma. A case report.
AB  - BACKGROUND: Fine needle aspiration (FNA) diagnosis of pilomatrixoma is rare. The
      cytologic presentation can be mistaken for squamous cell carcinoma because of
      high cellularity, high nuclear/cytoplasmic ratio and presence of anucleate
      squames. CASE: A 25-year-old male presented to Cook County Hospital with a slowly
      enlarging neck mass of three months' duration. FNA was interpreted as consisted
      with pilomatrixoma. Subsequently the patient had the mass removed. Histology
      confirmed the diagnosis of pilomatrixoma. CONCLUSION: The wide range of cell
      differentiation in conjunction with pertinent clinical findings, absence of
      nuclear atypia, tumor diathesis, mitotic figures and awareness of the entity lead
      to the correct diagnosis of pilomatrixoma.

PMID- 9622705
TI  - Microfilaria in a fine needle aspirate of primary solid malignant tumor of the
      maxillary antrum. A case report.
AB  - BACKGROUND: Lymphatic filarial disease is very common in tropical countries like
      India. The incidental finding of microfilariae in various benign cytologic smears
      is very common. Microfilariae in malignant effusions have also been reported, but
      their coexistence with solid malignant tumor at the primary site has not been
      reported so far. CASE: A 45-year-old male presented with a painful, rapidly
      growing swelling over the right maxilla that had been present for three months.
      On routine fine needle aspiration cytology, a microfilaria along with squamous
      carcinoma cells in a primary solid malignant tumor of the maxillary antrum was
      found. CONCLUSION: This is the first case reported in English of the incidental
      finding of a microfilaria in a primary tumor of the maxillary antrum.

PMID- 9622706
TI  - Pigmented neuroectodermal tumor of infancy in the epididymis. A case report.
AB  - BACKGROUND: Pigmented neuroectodermal tumor of infancy (PNTI) is a rare
      pigmentary tumor. Cytologic study of this tumor had not been performed before. In
      the present study, cytology of such a tumor was done in addition to histology,
      electron microscopy and immunohistochemistry. CASE: A 5-month-old infant had a
      scrotal tumor. After tumorectomy, touch smear for cytology revealed small and
      large tumor cells. The small cells showed a high nuclear/cytoplasmic ratio, and
      the large cells contained pigment in their cytoplasm. Histologically, the small
      cells and large, pigmented cells showed a typical alveolar and tubular pattern,
      respectively. The small cells neuroblastlike and the large cells showed
      melanocytelike features ultrastructurally and immunohistochemically. CONCLUSION:
      Cytology has not been applied to the diagnoses of PNTI. In our opinion, fine
      needle aspiration cytology could be helpful in the preoperative diagnosis of this
      tumor.

PMID- 9622707
TI  - Microfilariae in a cytologic smear from cavernous hemangioma of the liver. A case
      report.
AB  - BACKGROUND: Wuchereria bancrofti has been found in almost every tissue except the
      liver. CASE: Microfilariae were found in a hemangioma of the liver on fine needle
      aspiration in a 40-year-old female with pyrexia associated with hepatomegaly and
      a peripheral blood smear negative for microfilariae. CONCLUSION: Absence of
      microfilariae in a peripheral blood smear does not exclude filarial infection.

PMID- 9622709
TI  - Cytology of pigmented renal cell carcinoma. A case report.
AB  - BACKGROUND: Pigmented renal cell carcinoma is very rare, and there have been no
      reports on its cytologic findings. CASE: A 40-year-old female with pigmented
      renal cell carcinoma had cytologic findings similar to those of clear cell
      carcinoma except for the presence of melaninlike brown pigment. CONCLUSION: It is
      important to recognize that renal cell carcinoma may contain melaninlike brown
      pigment seen on cytologic examination of renal aspirates.

PMID- 9622708
TI  - Metastatic laryngeal basaloid squamous cell carcinoma simulating primary small
      cell carcinoma of the lung on fine needle aspiration lung biopsy. A case report.
AB  - BACKGROUND: First described in 1986, the basaloid squamous variant of laryngeal
      carcinoma is an uncommon, aggressive neoplasm with early presentation of
      metastatic disease and widespread dissemination. It is characterized primarily by
      its biphasic morphologic appearance. CASE: A 64-year-old female smoker presented
      with left hilar and right lower lung lobe masses. The fine needle aspiration
      cytologic findings were consistent with features of primary undifferentiated
      small cell carcinoma. CONCLUSION: The basaloid squamous cell carcinoma of head
      and neck region is a highly malignant neoplasm with frequent metastatic disease
      at the time of diagnosis. Metastatic deposits may consist of basaloid and/or
      squamous carcinoma cells. The basaloid component of this biphasic neoplasm is
      poorly differentiated and demonstrates cytologic features that mimic
      undifferentiated small cell carcinoma. Previous reports of cervical lymph node
      metastases from basaloid squamous carcinoma indicate frequent misdiagnosis as
      small cell carcinoma. Pulmonary metastases are more problematic since they
      introduce the possibility of a second primary lesion in these patients who have a
      frequent history of cigarette and/or ethanol abuse. Immunohistochemistry is
      useful in the distinction of metastatic basaloid squamous carcinoma from a second
      primary cell carcinoma of the lung.

PMID- 9622710
TI  - Basement membrane material (hyaline globules) in synovial sarcoma. A case report
      with description of a potential diagnostic pitfall.
AB  - BACKGROUND: Synovial sarcoma (SS), a malignant mesenchymal tumor, has a biphasic
      growth pattern characteristically. Histologically and cytologically the tumor can
      pose diagnostic difficulty when the epithelial component is predominant. CASE
      REPORT: A 22-year-old female presented with a rapidly enlarging mass on the lower
      left side of the neck. Fine needle aspiration of the tumor yielded abundant,
      discohesive round-oval cells mingled with amorphous hyaline material, raising a
      suspicion of medullary carcinoma of the thyroid. In addition, air-dried, Giemsa
      stained smears demonstrated rosettelike structures with central magenta globular
      material, mimicking adenoid cystic carcinoma. However, histologic examination of
      the excised tumor, including immunohistochemical and ultrastructural studies,
      proved it to be a typical SS with copious basement membrane accumulations.
      CONCLUSION: The cytologic appearance of SS can be confusing. However, a false
      diagnosis may be avoided if adequate needle sampling is ensured and clinical
      correlation considered.

PMID- 9622711
TI  - Metastatic squamous cell carcinoma in a liver graft. Report of a case diagnosed
      by fine needle aspiration.
AB  - BACKGROUND: Fine needle aspiration is a well-established and safe method for the
      diagnosis of focal liver lesions, but it has played a limited role in the
      transplant setting. CASE: A case of metastatic squamous cell carcinoma in a liver
      graft was diagnosed by fine needle aspiration. The tumor developed in the right
      pyriform sinus five years after an orthotopic liver transplantation was
      performed. CONCLUSION: With the improvement of survival rates following liver
      transplantation, metastatic tumors should be considered in liver grafts with
      space-occupying lesions. Therefore, fine needle aspiration is adequate for
      diagnosis and is cost-effective and safe.

PMID- 9622712
TI  - Fine needle aspiration cytology of hepatoblastoma. A report of two cases.
AB  - BACKGROUND: Hepatoblastoma is the most common primary hepatic tumor in children.
      The literature contains few examples of fine needle aspiration (FNA) cytology of
      these tumors. CASES: A 5-month-old and 4-month-old underwent ultrasonography
      guided FNA for the preoperative investigation of hepatic masses. The smears were
      stained with May-Grunwald-Giemsa and Papanicolaou stain. Alcohol-fixed smears
      were used for immunocytochemistry. All smears revealed cells with round/oval
      nuclei, prominent nucleoli and vacuolated cytoplasm, arranged in groups and
      acinar structures. The groups were embedded in a myxoid stroma. alpha-Fetoprotein
      was positive in all, and vimentin was positive in some tumor cells. The cytologic
      findings resembled the histologic counterpart in one case, and the other case
      agreed with the clinical/radiologic prediagnosis. Immunocytochemistry was
      supportive. CONCLUSION: FNA cytology can be diagnostic in many other childhood
      tumors as well as hepatoblastomas. Detailed descriptions of cytomorphologic
      features of hepatoblastoma will help FNA to be used confidently on these tumors.

PMID- 9622714
TI  - Fibromatosis of the breast: diagnosis by fine needle aspiration cytology.

PMID- 9622713
TI  - Persistent infection with human polyomavirus revealed by urinary cytology in a
      patient with heart transplantation. A case report.
AB  - BACKGROUND: Management after heart transplantation must deal with the twin risks
      of rejection and infection. Early infection with viral infection, particularly
      cytomegalovirus (CMV), is becoming more prevalent two to three months after
      transplantation. To our knowledge, there has been no previous report of human
      polyomavirus (HPOV) infection after heart transplantation. CASE: A 20-year-old
      male with a history of Kawasaki disease and who had suffered from severe
      congestive heart failure after a coronary artery bypass graft, underwent heart
      transplantation. Urinary cytology demonstrated HPOV infection, the diagnosis of
      which was established by the immunoperoxidase technique, in situ hybridization
      and electron microscopy. CONCLUSION: The definitive diagnosis of HPOV infection
      after a heart transplant can be made on urinary cytology.

PMID- 9622715
TI  - Invasive lobular breast carcinoma mimicking medullary carcinoma.

PMID- 9622716
TI  - Microfilariae in bone marrow aspiration smears.

PMID- 9622717
TI  - Pseudohyphae of Cryptococcus in a cytologic specimen.

PMID- 9622718
TI  - Metastatic mesothelioma presenting as a salivary gland neoplasm.

PMID- 9622719
TI  - Fine needle aspiration biopsy of Langerhans cell histiocytosis of bone: are
      ancillary studies necessary for a "definitive diagnosis"?

PMID- 9622720
TI  - Nuclear groves in vaginal cells.

PMID- 9622721
TI  - Hepatocellular carcinoma metastatic to the parotid gland: initial diagnosis by
      fine needle aspiration biopsy.

PMID- 9622722
TI  - Aspiration cytology of parathyroid adenoma: radioimmunoassay of parathormone in
      aspirate as a helpful diagnostic tool.

PMID- 9622723
TI  - Actinomycosis in a lymph node diagnosed by fine needle aspiration cytology.

PMID- 9622724
TI  - Automatic fine needle aspiration pistol specially designed for small tumors.

PMID- 9622725
TI  - Fine needle aspiration of mucocelelike lesions: differential diagnosis with
      colloid carcinoma.

PMID- 9622726
TI  - Violinist's or musician's nodule.

PMID- 9622727
TI  - Diagnosis of primary pancreatic lymphoma by fine needle aspiration.

PMID- 9622728
TI  - False negative rate in mass screening for cervical cancer.

PMID- 9622729
TI  - Primary amyloidoma (amyloid tumor) of soft tissue.

PMID- 9622730
TI  - Fine needle aspiration cytology of the cutaneous manifestation of primary
      sinonasal plasmacytoma.

PMID- 9622731
TI  - Microfilariae of Wuchereria bancrofti identified in a cervicovaginal smear.

PMID- 9622732
TI  - Identification and purification of apolipoprotein C-III from the serum of cows.
AB  - OBJECTIVE: To identify, purify, and analyze distribution of apolipoprotein C-III
      in lipoprotein fractions and to evaluate its concentration in serum from calves,
      heifers, and cows during various stages of lactation. SAMPLE POPULATION: Sera
      from 3 female calves, 3 heifers, and 12 cows during early, middle, late, and
      nonlactation stages. PROCEDURE: Apolipoprotein C-III was identified by use of
      amino-terminal amino acid sequence analysis of bands separated by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis. Purification was performed by
      extraction with acetone, delipidation with 2-propanol, and 2 chromatographic
      steps. The apolipoprotein C-III concentration in the total lipoprotein fraction
      was evaluated by densitometric scanning of the bands for apolipoprotein C-III
      separated by electrophoresis, using purified apolipoprotein C-III as an internal
      standard. RESULTS: Apolipoprotein C-III was identified as 8.2- and 7.3-kd
      proteins with identical amino acid sequences. The 2 proteins were mainly found in
      the high-density lipoprotein fraction, then were purified separately. Serum
      apolipoprotein C-III concentration was significantly (P < 0.05) higher in cows
      during lactation than in nonlactating cows and was negatively correlated with
      serum triglyceride concentration (r = -0.620, P < 0.01). CONCLUSIONS: The role of
      apolipoprotein C-III in cows may involve a function related to lactation.

PMID- 9622733
TI  - Ultrasonographic assessment of bladder neck mobility in continent bitches and
      bitches with urinary incontinence attributable to urethral sphincter mechanism
      incompetence.
AB  - OBJECTIVE: To determine bladder neck positional changes between standing and
      recumbent positions in bitches and whether change is related to continence status
      or general anesthesia, or both, and to evaluate reproducibility of measurements.
      ANIMALS: 45 continent animals and 46 incontinent bitches with urethral sphincter
      mechanism incompetence (SMI). PROCEDURE: Distance between the bladder neck and
      perineal skin was measured ultrasonographically via the perineum while each dog
      was conscious in standing and right lateral recumbency and in right lateral
      recumbency under general anesthesia. Measurements of the bladder neck position
      obtained in right lateral recumbency under anesthesia were compared with
      radiographic measurements of the same parameter. Reproducibility of the
      ultrasonographic measurements of the distance between bladder neck and perineum
      was assessed on 3 occasions for each position in 50 dogs. RESULTS: In all dogs,
      differences in bladder neck position between standing and recumbent conscious
      associated positions were not significant. However, caudal bladder neck movement
      between standing conscious- and recumbent anesthesia-associated positions and
      between recumbent conscious- and anesthesia-associated positions was significant
      for all dogs. Incontinent bitches had greater degree of caudal bladder movement
      during anesthesia. Mean difference in bladder neck positions between recumbent
      conscious- and recumbent anesthesia-associated positions was 0.24 cm in
      continent, compared with 0.73 cm in incontinent, bitches. Radiographic
      measurements were significantly greater than ultrasonographic measurements.
      Differences between repeated measurements for standing position were not
      significant, but those for recumbent conscious- and recumbent anesthesia
      associated positions were significant. CONCLUSIONS: Additional vesicourethral
      support mechanisms in continent dogs, are deficient in bitches with SMI, allowing
      the bladder neck to move further caudad.

PMID- 9622734
TI  - Kinematic gait analysis of hind limb symmetry in dogs at the trot.
AB  - OBJECTIVE: To describe intratrial differences in hind limb symmetry in healthy
      dogs at the trot, using noninvasive, computer-assisted, three-dimensional
      kinematic gait analysis. ANIMALS: 8 clinically normal large-breed adult dogs.
      PROCEDURE: Dynamic flexion and extension angles and angular velocities were
      calculated for the coxofemoral, femorotibial, and tarsal joints of dogs at the
      trot. Temporal and distance variables were computed. Essential Fourier
      coefficients were used to determine mean flexion and extension curves for all
      joints and to compare differences in movement between right and left hind limbs.
      Variances attributable to limb, dog, and trial were determined. RESULTS: Each
      joint had a characteristic pattern of flexion and extension movement that was
      used to compare intratrial symmetry of hind limb gait. Significant differences
      were not detected in temporal or distance variables between the right and left
      hind limbs. Significant differences were not noted in essential Fourier
      coefficients used to characterize coxofemoral, femorotibial, and tarsal joint
      angles and angular velocities, with the exception of the cosine-0 coefficient for
      coxofemoral angular velocity. Variation in joint angle and angular velocity
      measurements were attributable to individual dog and trial. Variation
      attributable to limb was negligible. CONCLUSIONS: Intratrial evaluation of right
      left hind limb symmetry, using kinematic gait analysis, indicated objectively
      that hind limb movement is symmetrical at the trot in healthy large-breed dogs.
      CLINICAL RELEVANCE: Documentation of hind limb symmetry at the trot will help
      provide a basis for direct comparison of both hind limbs in future studies
      evaluating gait and treatment of dogs with musculoskeletal disease.

PMID- 9622735
TI  - Diagnostic value of full-mouth radiography in dogs.
AB  - OBJECTIVE: To determine the diagnostic value of full-mouth radiography in dogs.
      SAMPLE POPULATION: Prospective series of 226 dogs referred for dental treatment
      without previous full-mouth radiographic views being available. PROCEDURE: In a
      prospective nested case-control analysis of multiple outcomes in a hospital
      cohort of dogs presented for dental treatment, full-mouth radiographic views were
      obtained prior to oral examination and charting. After treatment, clinical and
      radiographic findings were compared, with reference to presenting problems, main
      clinical findings, additional information obtained from the radiographs, and
      unexpected radiographic findings. The importance of the radiographic findings in
      therapeutic decision-making was assessed. RESULTS: The main clinical findings
      were radiographically confirmed in all dogs. Selected presenting problems and
      main clinical findings yielded significantly increased odds ratios for a variety
      of other conditions, either expected or unexpected. Radiographs of teeth without
      clinical lesions yielded incidental or clinically important findings in 41.7 and
      27.8% of dogs, respectively, and were considered of no clinical value in 30.5%.
      Radiographs of teeth with clinical lesions merely confirmed the findings in 24.3%
      of dogs, yielded additional or clinically essential information in 50.0 and
      22.6%, respectively, and were considered of no value in 3.1%. Older dogs derived
      more benefit from full-mouth radiography than did younger dogs. Incidental
      findings were more common in larger dogs. CLINICAL RELEVANCE: Diagnostic yield of
      full-mouth radiography in new canine patients referred for dental treatment is
      high, and the routine use of such radiographs is justifiable.

PMID- 9622736
TI  - Diagnostic value of full-mouth radiography in cats.
AB  - OBJECTIVE: To determine the diagnostic value of full-mouth radiography in cats.
      SAMPLE POPULATION: 115 cats referred for dental treatment without a previous full
      mouth radiographic series available. PROCEDURE: In a prospective nested case
      control analysis of multiple outcomes in a hospital cohort of cats referred for
      dental treatment, full-mouth radiography was done prior to oral examination and
      charting. After treatment, the clinical and radiographic findings were compared,
      with reference to presenting problems, main clinical findings, additional
      information obtained from radiography and unexpected radiographic findings.
      Importance of the radiographic findings in therapeutic decision making was
      assessed. RESULTS: The main clinical findings were radiographically confirmed in
      all cats. Odontoclastic resorption lesions, missed on clinical examination, were
      diagnosed in 8.7% of cats. Analysis of selected presenting problems and main
      clinical findings yielded significantly increased odds ratios for a variety of
      other conditions, either expected or unexpected. Radiographs of teeth without
      clinical lesions yielded incidental or clinically important findings in 4.8 and
      41.7% of cats, respectively, and were considered of no clinical value in 53.6%.
      Radiographs of teeth with clinical lesions merely confirmed the findings in 13.9%
      of cats, but yielded additional or clinically essential information in 53.9 and
      32.2%, respectively. CLINICAL RELEVANCE: The diagnostic yield of full-mouth
      radiography in new feline patients referred for dental treatment is high, and
      routine use of full-mouth radiography is justifiable.

PMID- 9622737
TI  - Role of the large intestine in the pathogenesis of diarrhea in weaned pigs.
AB  - OBJECTIVE: To determine whether the large intestine may have a role in
      counterbalancing the loss of fluid from the small intestine of pigs with
      diarrhea. ANIMALS: 2 groups of pigs (1 from a specific-pathogen-free herd and 1
      from a herd with a history of diarrhea). PROCEDURE: At weaning and 4, 7, 11, and
      14 days after weaning, the percentage of dry matter in the large intestinal
      contents, total and individual concentrations and volatile fatty acids in large
      intestinal contents and blood, and concentration of aldosterone in the blood were
      measured. RESULTS: Large intestinal contents of pigs with diarrhea had a lower
      percentage of dry matter, lower acetate and butyrate concentrations, and higher
      propionate concentrations than did those of specific-pathogen-free pigs, and
      blood of pigs with diarrhea also had lower total volatile fatty acids
      concentration, higher aldosterone concentration, and lower sodium concentration.
      CLINICAL RELEVANCE: The large intestine has a role in the pathogenesis of
      diarrhea in weaned pigs.

PMID- 9622738
TI  - CLoning of equine interleukin 1 alpha and equine interleukin 1 beta and
      determination of their full-length cDNA sequences.
AB  - OBJECTIVES: To clone equine interleukin 1 alpha (IL-1 alpha) and equine
      interleukin 1 beta (IL-1 beta) and determine their full-length cDNA sequences.
      PROCEDURES: The mRNA isolated from lipopolysaccharide-stimulated cultured equine
      monocytes was reverse transcribed, and a cDNA library was constructed in a lambda
      phage. The cDNA library was screened by means of plaque hybridization with
      radiolabeled human IL-1 alpha and IL-1 beta cDNA probes. The cDNA nucleotide
      sequences for equine IL-1 alpha and equine IL-1 beta were determined by use of
      the dideoxy chain termination technique. The cDNA sequences were analyzed, using
      computer software, for sequence characteristics and compared with sequences
      reported for other species. RESULTS: The cDNA for equine IL-1 alpha was 1,728
      base pairs in length with an ORF encoding a peptide of 270 amino acids with a
      predicted molecular mass of 30.823 kd. The cDNA for equine IL-1 beta was 1,473
      base pairs in length with an ORF encoding a peptide of 268 amino acids with a
      predicted molecular mass of 30.342 kd. Similarity between amino acid sequence of
      equine IL-1 alpha and sequences for IL-1 alpha of other species ranged from 62.5
      to 82.2%; similarity between amino acid sequence of equine IL-1 beta and
      sequences for IL-1 beta of other species ranged from 62.5 to 82.2%; similarity
      between amino acid sequences of equine IL-1 alpha and equine IL-1 beta was 26%.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results establish a basis for studying the
      roles of interleukin 1 in healthy and diseased joints in horses.

PMID- 9622739
TI  - Cloning of equine interleukin 1 receptor antagonist and determination of its full
      length cDNA sequence.
AB  - OBJECTIVES: To clone equine interleukin 1 receptor antagonist (IL-1ra) and
      determine its full-length cDNA sequence. PROCEDURE: A cDNA library derived from
      lipopolysaccharide-stimulated equine monocytes was screened by means of plaque
      hybridization to radiolabeled equine IL-1ra DNA probes generated by means of the
      polymerase chain reaction. The cDNA nucleotide sequence for equine IL-1ra was
      determined by use of the dideoxy chain termination technique, analyzed by use of
      computer software for sequence characteristics, and compared with sequences
      reported for IL-1ra of other species. RESULTS: The cDNA of equine IL-1ra was
      1,614 base pairs in length with an ORF encoding a peptide of 177 amino acids with
      a predicted molecular mass of 20.427 kd. Similarity between the amino acid
      sequence of equine IL-1ra and sequences for human, murine, rat, and lapine IL-1ra
      was 76%. Similarity between sequence for equine IL-1ra and sequences for equine
      interleukin-1 alpha and equine interleukin-1 beta were 22.6 and 24.6%,
      respectively. CONCLUSION: Comparison of the sequence for equine IL-1ra with
      sequences for IL-1ra of other species indicated a high degree of conservation.
      CLINICAL RELEVANCE: Results establish a basis for studying the roles of
      interleukin-1 in healthy and diseased joints in horses.

PMID- 9622740
TI  - Induction of cytokine messenger RNA transcripts in mouse macrophages by Listeria
      monocytogenes isolated from channel catfish.
AB  - OBJECTIVE: To determine whether differences exist in induction and quantity of
      tumor necrosis factor alpha (TNF-alpha), interleukin (IL)1 beta, and IL-10 mRNA
      transcripts when mouse J774A.1 macrophages are infected with Listeria
      monocytogenes, including 2 isolates originating from channel catfish, the wild
      type virulent (EGD) strain, and a nonhemolytic strain (ATCC 15313). SAMPLES:
      Listeria monocytogenes isolates from kidneys or fillets of channel catfish were
      used to stimulate cytokine production from mouse macrophages. The RNA from the
      infected macrophages was collected. PROCEDURE: Four hours after infection with L
      monocytogenes, total cellular RNA was extracted from the J774A.1 cells and
      reversed transcribed to cDNA, which was amplified, using specific primers for TNF
      alpha, IL-1 beta, or IL-10. The specific amplified DNA fragments were detected on
      polyacrylamide gels and quantified, using a reverse transcription polymerase
      chain reaction (PCR)-mediated ELISA. RESULTS: The wild-type hemolytic EGD strain
      and the 2 hemolytic catfish isolates of L monocytogenes induced higher amounts of
      TNF-alpha-, IL-1 beta-, and IL-10-specific mRNA in J774A.1 cells than did the
      nonhemolytic strain. CONCLUSIONS: Hemolysin-associated induction of TNF-alpha, IL
      1 beta, and IL-10 cytokines may be related to survival and replication of L
      monocytogenes in macrophages. It also suggests that the PCR-mediated ELISA
      procedure is a sensitive test to quantify cytokines from cell cultures.

PMID- 9622741
TI  - Evaluation of antemortem polymerase chain reaction and serologic methods for
      detection of Lawsonia intracellularis-exposed pigs.
AB  - OBJECTIVE: To evaluate polymerase chain reaction (PCR) for detection of Lawsonia
      intracellularis DNA in feces and an indirect fluorescent antibody test (IFAT) for
      detecting serum IgG antibodies in pigs exposed to L intracellularis. ANIMALS: 15
      seven-week-old pigs and 42 three-week-old pigs. PROCEDURE: During 3 experiments,
      23 pigs were inoculated with a pure culture of L intracellularis, 31 pigs served
      as noninoculated controls, and 3 pigs were used as sentinels. Fecal shedding of L
      intracellularis was monitored by use of PCR analysis at 7-day intervals. At
      euthanasia, the ileum was obtained for PCR and histologic analyses. Serum was
      obtained at 7-day intervals for use in the IFAT. RESULTS: Polymerase chain
      reaction analysis detected L intracellularis DNA in the feces of 39% of the
      inoculated pigs; by postinoculation days 21 to 28, 90% of inoculated pigs
      developed IgG antibodies detected by IFAT. Neither L intracellularis DNA nor IgG
      antibodies were detected in any of the noninoculated control pigs at euthanasia.
      Sera from pigs inoculated with enteric pathogens other than L intracellularis did
      not contain detectable antibodies that reacted with L intracellularis by use of
      the IFAT. CONCLUSION: The IFAT for L intracellularis IgG antibody detection
      appeared to be a more sensitive antemortem test for detecting pigs experimentally
      infected with L intracellularis than was a PCR method for direct detection of the
      organism in the feces. CLINICAL RELEVANCE: Not all animals that are infected with
      L intracellularis shed the organism in feces at detectable amounts.

PMID- 9622743
TI  - Supplemental dietary biotin for prevention of lesions associated with aseptic
      subclinical laminitis (pododermatitis aseptica diffusa) in primiparous cows.
AB  - OBJECTIVE: To evaluate, in primiparous cows, the effect of dietary biotin
      supplementation on severity of lesions of aseptic subclinical laminitis. ANIMALS:
      100 primiparous cows in a 800-cow commercial dairy herd. PROCEDURE: Cows were
      assigned after calving to a biotin-supplemented (20 mg/head/d) or control group
      on an alternating basis. Digits 3 and 4 of the left forelimb and right hind limb
      were examined at a mean of 25, 108, and 293 days after parturition. Toe length,
      hoof angle, and heel depth were measured, and hooves were examined for solear
      hemorrhage, yellow solear discoloration, separation of the white line, and heel
      erosion. Serum and milk biotin concentrations were also measured. RESULTS: Serum
      biotin concentrations were significantly higher for supplemented than for control
      cows. During the second examination, prevalence of separation of the white line
      of digits 3 and 4 of the hind limb and digit 4 of the forelimb was lower for
      supplemented than for control cows. Mean decrease in heel depth between the first
      and third examinations was approximately twice as great for digit 4 of the
      forelimb and 4 times as great for digit 3 of the forelimb in supplemented, versus
      control, cows. Other differences were not found. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results suggest that supplemental dietary biotin may have a beneficial
      effect on hoof health in intensively managed primiparous dairy cows.

PMID- 9622742
TI  - Antibody responses to Pasteurella haemolytica 1:A and three of its outer membrane
      proteins in serum, nasal secretions, and bronchoalveolar lavage fluid from
      calves.
AB  - OBJECTIVE: To determine systemic and mucosal antibody responses in calves to
      Pasteurella haemolytica 1:A and to 2 major outer membrane proteins (OMP) and 1
      major iron-regulated OMP of P haemolytica 1:A. ANIMALS: 23 crossbred calves.
      PROCEDURE: 2 experiments were performed in the first experiment, 6 calves were
      vaccinated and challenge exposed intranasally with an aerosol of P haemolytica
      1:A and 6 calves were only challenge exposed. In the second experiment, 8 calves
      were vaccinated in the area of the tracheal bifurcation with an aerosol of P
      haemolytica 1:A and 3 calves were used as controls. Serum, nasal secretions, and
      bronchoalveolar lavage (BAL) samples were collected, and IgG1, IgG2, IgA, and IgM
      titers were determined. Nasal secretions and BAL samples were also submitted for
      bacterial culture. RESULTS: Serum antibody responses in the 2 groups were
      similar. Antibody titers in nasal secretions and BAL samples increased in calves
      vaccinated intranasally. In calves vaccinated in the area of the tracheal
      bifurcation, antibody titers increased in BAL samples but not in nasal
      secretions. Antibody responses did not correlate with results of bacterial
      culture. CONCLUSIONS: Results indicated that intranasal administration of P
      haemolytica 1:A may be a better method for stimulating protective immune
      responses in the upper portion of the respiratory tract than lung administration.
      The single dilution ELISA provided a reliable and economical method for
      determining antibody titers.

PMID- 9622744
TI  - Stereospecific pharmacokinetics of free and protein-bound ketoprofen in serum and
      synovial fluid of horses after intravenous and intramuscular administration.
AB  - OBJECTIVE: To determine intravascular and intrasynovial pharmacokinetics of the R
      and S enantiomers of ketoprofen after i.v. and i.m. administration to horses.
      ANIMALS: 6 healthy adult mares. PROCEDURE: Horses were weighed and ketoprofen
      (2.2 mg/kg of body weight) was administered i.v. Blood and synovial fluid samples
      were obtained and analyzed for concentrations of the R and S enantiomers by means
      of a modified reverse-phase stereospecific high-pressure liquid chromatographic
      method. Three weeks later, the procedure was repeated, except that ketoprofen was
      given IM. Protein binding of ketoprofen enantiomers was determined by means of
      ultrafiltration. Nonlinear least squares methods were used to calculate
      pharmacokinetic parameters. RESULTS: Data obtained after i.v. administration best
      fit an open, two-compartment model. Mean +/- SD S-to-R serum concentration ratios
      after i.v. and i.m. administration were 1.36 +/- 0.214 and 1.34 +/- 0.245,
      respectively. Intrasynovial concentrations of the R and S enantiomers of
      ketoprofen could be measured for only the first 3 hours after i.v.
      administration; concentrations were less than the limit of quantification by 4
      hours after i.v. administration and at all times after i.m. administration.
      Extent of protein binding of the R enantiomer was not significantly different
      from extent of protein binding of the S enantiomer; extent of protein binding did
      not appear to be concentration dependent. Mean free S-to-free R serum
      concentration ratios, adjusted for protein binding, after i.v. and i.m.
      administration were 1.58 and 1.56, respectively. CONCLUSIONS: The R and S
      enantiomers of ketoprofen are rapidly absorbed and eliminated, have low volumes
      of distribution, and are highly protein bound.

PMID- 9622745
TI  - Impaired cytosolic calcium mobilization and aggregation in response to collagen
      in platelets from Japanese black cattle with Chediak-Higashi syndrome.
AB  - OBJECTIVE: To examine whether impaired aggregation of platelets from Japanese
      Black cattle with Chediak-Higashi syndrome (CHS) was attributable to mobilization
      of cytosolic Ca2+. ANIMALS: 4 healthy Japanese Black cattle and 3 Japanese Black
      cattle with CHS. PROCEDURE: Aggregation and mobilization of cytosolic Ca2+ in
      response to various receptor agonists was measured in platelets from healthy
      cattle and cattle with CHS. Involvement of endogenous ADP and arachidonic acid in
      collagen-induced responses was examined. Cytosolic Ca2+ concentration was
      measured after platelets were loaded with the Ca2+ indicator fura-PE3. Platelet
      aggregation was measured with an aggregometer. RESULTS: Collagen (3 to 15
      micrograms/ml)-induced increases in cytosolic Ca2+ concentration and aggregation
      were markedly impaired for platelets from cattle with CHS, compared with values
      for platelets from healthy cattle. Although aggregation and the sustained phase
      of the cytosolic Ca2+ response to ADP were also decreased in platelets from
      cattle with CHS, these decreases were small, compared with those in response to
      collagen. A cyclooxygenase inhibitor and a phospholipase A2 inhibitor did not
      have any effect on peak cytosolic Ca2+ concentration or collagen-induced
      aggregation of platelets from healthy cattle. Responses to a P2 tau-purinoceptor
      antagonist suggested that decreased release of endogenous ADP was only partially
      involved in the impaired response to collagen among platelets from cattle with
      CHS. CONCLUSIONS AND CLINICAL RELEVANCE: Marked inhibition of collagen-induced
      Ca2+ mobilization, rather than decreased release of endogenous substances,
      appeared to be the major cause of impaired platelet response to collagen and the
      hemorrhagic tendency in cattle with CHS.

PMID- 9622746
TI  - Comparison of amikacin dosing regimens in neutropenic guinea pigs with
      Escherichia coli infection.
AB  - OBJECTIVE: To derive pharmacokinetic data for 3 amikacin dosing regimens in
      guinea pigs and to determine whether the antibacterial activity of 15 mg/kg of
      body weight given twice daily is equivalent to administering the drug more
      frequently. ANIMALS: 10 guinea pigs in pharmacokinetic trials, and 10 guinea pigs
      in pretreatment, control, and amikacin treatment groups. PROCEDURE: Amikacin
      pharmacokinetic data were determined in guinea pigs after single i.m.
      administration of 3.75, 7.5 and 15 mg/kg. Guinea pigs had been made neutropenic
      by treatment with cyclophosphamide. All guinea pigs were inoculated with 2.8 x
      10(8) colony-forming units (CFU) of Escherichia coli in the thigh muscle, then
      were allotted to 5 groups: pretreatment (euthanized 4 hours after inoculation),
      control, and 3 amikacin treatment groups (3.75 mg/kg, q 3 h; 7.5 mg/kg, q 6 h;
      and 15 mg/kg, q 12 h). Amikacin administration was begun 4 hours after E coli
      inoculation and was continued for 72 hours. Numbers of E coli CFU in infected
      thigh muscle were determined for each guinea pig. RESULTS: Difference in survival
      between control and the amikacin-treated groups was significant. The E coli
      infection concentration (log10 CFU) increased significantly in the control,
      compared with the pretreatment, group. Infection concentration decreased
      significantly in all treatment groups, compared with the pretreatment group.
      There was no significant difference in bacterial killing among the 3 treatment
      groups. CONCLUSION: Amikacin had a significant effect on survival of neutropenic
      guinea pigs with E coli infection. Antibacterial activity did not differ among 3
      doses of amikacin administered at different intervals. CLINICAL RELEVANCE:
      Aminoglycoside dosing regimen with high peak concentration and long drug-free
      interval is as efficacious as divided dose regimens.

PMID- 9622747
TI  - Effects of medetomidine on serum osmolality; urine volume, osmolality and pH;
      free water clearance; and fractional clearance of sodium, chloride, potassium,
      and glucose in dogs.
AB  - OBJECTIVE: To determine effects of i.v. medetomidine administration on selected
      clinicopathologic variables in dogs. ANIMALS: 6 healthy adult Beagles. PROCEDURE:
      Dogs were randomly assigned to each of 3 treatments in a crossover study design.
      Serum osmolality, urine osmolality, urine pH, and fractional clearances of
      sodium, chloride, potassium, and glucose were determined before and 20, 40, 60,
      120, 180, 240, 300, 360, 420, and 480 minutes after i.v. administration of 0.9%
      NaCl (saline) solution (control) or medetomidine (10 or 20 micrograms/kg of body
      weight). The urinary bladder was emptied prior to saline or medetomidine
      administration, and urine volume was determined at the same posttreatment times
      as those described previously. Free water clearance was calculated for all
      posttreatment times. RESULTS: After medetomidine administration, serum
      osmolality, urine volume, free water clearance, and fractional clearance of
      potassium and glucose increased; urine osmolality decreased. Initially, urine pH
      and fractional clearance of chloride decreased, then subsequently increased.
      Fractional clearance of sodium did not change. CONCLUSIONS AND CLINICAL
      RELEVANCE: Because i.v. administration of medetomidine to dogs at dosages of 10
      and 20 micrograms/kg induces a diuretic effect that lasts up to 4 hours, the drug
      should be used with discretion in hypovolemic or dehydrated dogs, and its use
      should be avoided in those with urinary tract obstruction.

PMID- 9622748
TI  - Effect of finasteride on serum concentrations of dihydrotestosterone and
      testosterone in three clinically normal sexually intact adult male dogs.
AB  - OBJECTIVE: To determine the effect of finasteride at dosages of 0, 10, 0.25, and
      0.50 mg/kg of body weight, PO, q 24 h, for 7 days) in a Latin square design with
      repeated measures. Blood was obtained before and on days 1, 2, 4, and 7 of
      treatment; 3 blood samples were obtained at 20 minute intervals to detect
      pulsatile secretion of DHT and T. Dogs were untreated at least 2 weeks between
      treatments. RESULTS: Finasteride at all doses was associated with a mean decrease
      in concentration of DHT of 55% (range, 155 +/- 32.3 pg/ml to 70 +/- 15 pg/ml),
      but had no effect on concentration of T (before treatment, 2.6 +/- 0.38 ng/ml;
      after treatment, 2.2 +/- 0.63 ng/ml). CONCLUSIONS: Finasteride at these doses
      significantly decreased serum concentration of DHT in sexually intact adult male
      dogs. Concentrations of DHT and T before and 7 days after treatment did not
      differ by dosage of finasteride administered. CLINICAL RELEVANCE: Finasteride (5
      mg; 1 tablet) may be a drug of choice for treatment of benign prostatic
      hypertrophy in 10- to 50-kg dogs.

PMID- 9622749
TI  - Anti-inflammatory benefits of tilmicosin in calves with Pasteurella haemolytica
      infected lungs.
AB  - OBJECTIVES: To determine whether tilmicosin alters neutrophil infiltration or
      function, induces neutrophil apoptosis, and affects accumulation of leukotriene
      B4 (LTB4) or tumor necrosis factor-alpha (TNF-alpha) in lungs of calves
      experimentally infected with Pasteurella haemolytica. ANIMALS: 12 weight-ranked
      Holstein calves. PROCEDURE: Calves were given 25% propylene glycol vehicle (n =
      5) or tilmicosin (10 mg/kg of body weight; n = 6) subcutaneously, 18 hours and 15
      minutes before intratracheal infection with 2 x 10(8) P haemolytica organisms.
      Two unmanipulated calves served as controls in some experiments. Rectal
      temperatures were recorded 15 minutes before, and at 3-hour intervals after
      infection for 24 hours. Samples obtained from bronchoalveolar lavage performed 3
      and 24 hours after infection were used to assess colonization by P haemolytica,
      and neutrophil infiltration. Neutrophil phagocytosis of P haemolytica, membrane
      leakage as determined by trypan blue exclusion, oxidative function as determined
      by nitro blue tetrazolium reduction, and apoptosis, using electron microscopy and
      DNA fragmentation ELISA, were determined. SOluble TNF-alpha and LTB4 were
      measured from supernatants from bronchoalveolar lavage samples, using ELISA.
      RESULTS: Treatment with tilmicosin resulted in significant (P < 0.05) clearance
      of P haemolytica and neutrophil apoptosis at 3 hours, and decreased concentration
      of LTB4 at 24 hours. Rectal temperatures, neutrophil infiltration, phagocytosis,
      oxidative functions, membrane leakage, and soluble TNF-alpha concentrations were
      not significantly affected by tilmicosin. CONCLUSION: Tilmicosin effectively
      controlled P haemolytica infection, induced neutrophil apoptosis, reduced
      pulmonary inflammation, and did not affect neutrophil infiltration or function.
      CLINICAL RELEVANCE: By inducing neutrophil apoptosis, tilmicosin prevents further
      amplification of inflammatory injury in P haemolytica-infected lungs.

PMID- 9622750
TI  - Morphologic changes and xanthine oxidase activity in the equine jejunum during
      low flow ischemia and reperfusion.
AB  - OBJECTIVE: To determine whether xanthine oxidase and dehydrogenase activities are
      altered during low flow ischemia and reperfusion of the small intestine of
      horses. ANIMALS: 5 clinically normal horses without histories of abdominal
      problems. PROCEDURE: With the horse under general anesthesia, a laparotomy was
      performed and blood flow to a segment of the distal jejunum was reduced to 20% of
      baseline for 120 minutes and was then reperfused for 120 minutes. Biopsy
      specimens were obtained before, during, and after ischemia for determination of
      xanthine oxidase and dehydrogenase activities, and for histologic and
      morphometric analyses. RESULTS: Percentage of xanthine oxidase activity (as a
      percentage of xanthine oxidase and dehydrogenase activity) was not altered during
      ischemia and reperfusion. An inflammatory response developed and progressed
      during ischemia and reperfusion. Mucosal lesions increased in severity after
      ischemia and reperfusion. Mucosal surface area and volume decreased during
      ischemia and continued to decrease during reperfusion. Submucosal volume
      increased slightly during ischemia, and continued to increase during reperfusion.
      CONCLUSIONS AND CLINICAL RELEVANCE: Evidence for conversion of xanthine
      dehydrogenase to xanthine oxidase during ischemia was not found. Factors other
      than production of reactive oxygen metabolites may be responsible for progressive
      epithelial loss, decrease in mucosal surface area and volume, and increase in
      submucosal volume observed in this study. Other methods of determining xanthine
      oxidase activity that detect the enzyme in sloughed epithelial cells should be
      used to better define the importance of this pathway in jejunal reperfusion
      injury in horses.

PMID- 9622751
TI  - Analysis of the electroencephalogram in growing calves by use of power spectrum
      and cross correlation.
AB  - OBJECTIVE: To determine postnatal maturation of findings in the
      electroencephalogram (EEG) of calves and estimate the degree of
      electrophysiologic activity, using power spectrum and cross-correlation analyses
      of the EEG. ANIMALS: 10 clinically normal Japanese Black calves ranging in age
      from 1 to 10 weeks. PROCEDURE: EEG were recorded at various stages of
      consciousness. Power spectrum and cross-correlation analyses were applied to a
      relaxed state EEG. RESULTS: After the second week of age, rhythmic waves with
      frequencies of 6 to 9 Hz (alpha rhythm-like pattern) appeared in the EEG during
      the relaxed state, and were recorded in the occipital and vertex areas; duration
      of appearance was < 30 seconds. By use of power spectrum analysis, power
      distribution of the 7.5- to 10-Hz frequency band in the occipital area
      significantly increased after the sixth week. The highest frequency (18 to 30 Hz)
      band increased in the frontal and occipital areas after the seventh week.
      Normalized cross-correlation coefficients at 0 time shift were > 0.6 throughout
      the experimental period. The normalized cross-correlation coefficients obtained
      from caudal interhemispheric sites increased after the second week, and were
      significantly greater than those in rostral sites. CONCLUSIONS AND CLINICAL
      RELEVANCE: Developmental changes in the EEG of calves during the first 10 weeks
      could be characterized by appearance of the alpha rhythm-like pattern and
      increase of the power distributions of the 7.5- to 10-Hz and 18- to 30-Hz
      frequency bands, which might be a useful indicator for estimating brain activity
      in young calves and as standard data for evaluating abnormal brain activity in
      calves.

PMID- 9622752
TI  - Skeletal muscle glycolytic capacity and phosphofructokinase regulation in horses
      with polysaccharide storage myopathy.
AB  - OBJECTIVE: To determine whether polysaccharide storage myopathy (PSSM) in Quarter
      Horses is attributable to a defect in glycolysis or in the allosteric regulation
      of phosphofructokinase (PFK) enzyme. ANIMALS: Muscle biopsy specimens were
      obtained from 6 Quarter Horses with PSSM and 8 Quarter Horse or Thoroughbred
      control horses. PROCEDURES: Maximal activity of glycogenolytic and glycolytic
      enzymes was determined spectrophotometrically. Maximal activity of PFK was
      determined for each horse at pH 8.0, and at pH 7.0 when variable concentrations
      of the activators, fructose 6 phosphate, fructose 2,6 bisphosphate, and adenosine
      monophosphate or inhibitors adenosine triphosphate and citrate were added to the
      reaction mixture. Relative activity was calculated as activity at pH 7/maximal
      PFK activity. RESULTS: Deficiencies in glycogenolytic or glycolytic enzyme
      activities were not evident in horses with PSSM. Differences between horses with
      PSSM and control horses in relative activity of PFK were not apparent for any of
      the activators or inhibitors used in the study. CONCLUSIONS: In a group of horses
      with PSSM, we were unable to detect a glycogenolytic or glycolytic enzyme
      deficiency or abnormality in the allosteric regulation of PFK. CLINICAL
      RELEVANCE: Although PSSM is clinically and histologically similar to
      glycogenolytic/glycolytic enzyme deficiencies in human beings and other animal
      species, abnormalities in this metabolic pathway are not present in horses with
      PSSM.

PMID- 9622753
TI  - Changes in sulfation patterns of chondroitin sulfate in equine articular
      cartilage and synovial fluid in response to aging and osteoarthritis.
AB  - OBJECTIVES: To determine effects of aging on sulfation of chondroitin sulfate
      (CS) in articular cartilage and synovial fluid from normal equine middle carpal
      joints, and to determine whether CS compositional analysis can be used to assess
      alterations in proteoglycan turnover in degenerative cartilage obtained from
      horses with carpal osteochondral fractures. SAMPLE POPULATION: Carpal articular
      cartilage and synovial fluid from 44 cadavers with normal joints and from 16
      Thoroughbred racehorses during routine carpal arthroscopic surgery. PROCEDURE:
      After papain/chondroitinase digestion of cartilage, CS disaccharides (unsulfated
      disaccharide delta Di0S, and monosulfated disaccharides delta Di4S and delta
      Di6S) were quantified by capillary zone electrophoresis. The CS was purified from
      synovial fluid chondroitinase digested, and analyzed. The CS nonreducing terminal
      residues, N-acetylgalctosamine (galNAc) or glucuronic acid adjacent to a 4
      sulfated or 6-sulfated galNAc, were quantified. RESULTS: In cartilage, the delta
      Di6S-to-delta Di4S ratio increased with age; in degenerative cartilage, this
      ratio was not significantly different from the normal value. Percentage of delta
      Di0S decreased with age and was significantly higher in degenerative than in
      normal cartilage. The galNAc4S and galNAc4,6S represented > or = 96% of the
      terminal residues. There was a significant decrease in 6-sulfation of the
      terminal residues in degenerative cartilage. CONCLUSIONS: 6-Sulfation of internal
      and terminal CS residues increased with age. Cartilage degeneration in racehorses
      was accompanied by deposition of CS chains with altered sulfation patterns, in
      normal and diseased joints of horses > 2 years old, synovial fluid CS was not
      indicative of cartilage CS and may represent turnover products of a subpopulation
      of proteoglycan within the matrix.

PMID- 9622755
TI  - Internet a valuable resource.

PMID- 9622754
TI  - Effect of tumor necrosis factor antibody given to horses during early
      experimentally induced endotoxemia.
AB  - OBJECTIVE: To test efficacy of murine monoclonal, rabbit polyclonal recombinant
      equine or human tumor necrosis factor-alpha (rETNF or rHTNF, respectively)
      antibodies to inhibit native equine tumor necrosis factor (TNF) activity.
      ANIMALS: 8 and 18 healthy adult horses for parts 1 and 2 of the study,
      respectively. PROCEDURES: In part 1, supernates from endotoxin-activated
      peritoneal macrophages were incubated with various dilutions of each rETNF
      antibody and subsequently tested for TNF activity. Serum was also obtained from a
      horse 1 hour after infusion with 20 ng of endotoxin/kg of body weight and was
      incubated with various dilutions of rabbit polyclonal rHTNF antibody. In part 2,
      20 ng of endotoxin/kg was infused in horses during a 30-minute period. Fifteen
      minutes after the endotoxin infusion was initiated, 1 of 3 preparations was
      infused: 0.1 mg of rabbit polyclonal (rHTNF antibody/kg, 0.1 mg of human IgG/kg,
      or 500 ml of 5% dextrose. Clinical and hematologic data were collected for 24
      hours. RESULTS: Compared with the monoclonal antibody, the rabbit polyclonal
      rETNF antibody was more effective in inhibiting TNF activity. The 50% effective
      doses of the murine monoclonal rETNF, rabbit polyclonal rETNF, and rabbit rHTNF
      antibodies were 1.8, 0.8, and 0.6 micrograms of antibody/ml, respectively. In
      part 2, endotoxin infusion resulted in significant alternations in all variables;
      however, differences among treatment groups were not significant. CONCLUSIONS AND
      CLINICAL RELEVANCE: Although murine monoclonal and rabbit polyclonal rETNF or
      rHTNF antibodies are capable of inhibiting native equine TNF activity in vitro,
      when given after initiation of endotoxemia, administration of 0.1 mg of rabbit
      polyclonal rHTNF/kg does not alter the response to infusion of endotoxin.

PMID- 9622756
TI  - Childhood and adolescent changes of skeletal relationships.
AB  - This paper describes the development of anteroposterior (AP) and vertical (VER)
      skeletal relationships. A mixed-longitudinal sample of 49 females and 50 males
      was followed during childhood and adolescence. Childhood growth changes were
      assessed from 6 to 10 years for females and 8 to 12 years for males. Adolescent
      changes were evaluated from 9 to 13 years for females and 11 to 15 years for
      males. Anteroposterior relationships were described by the horizontal distance
      between ANS and Pg. Vertical relationships were described by the vertical
      distance between Pg and Go. Subsamples were defined based on overall changes (AP
      and VER) that were either greater than or less than average. The results showed
      that AP and VER relationships were not stable during growth. AP relationships
      changed over time due to differential growth movements of the mandible (as
      opposed to the maxilla). There was greater potential for horizontal discrepancies
      to decrease during childhood than during adolescence. The potential for AP
      discrepancies to increase was greater during adolescence. The VER relationships
      increased in the majority of subjects. The subsample whose vertical discrepancies
      increased most showed less inferior movement of gonion and more inferior movement
      of pogonion. Inferior movements of Pg and Go were greater during adolescence than
      childhood.

PMID- 9622757
TI  - Changes in overbite and face height from 5 to 45 years of age in normal subjects.
AB  - The purpose of this study was to evaluate changes in overbite over a 40-year
      span, and to relate these changes to those occurring in vertical skeletal facial
      relationships. Lateral cephalograms of 20 males and 15 females from the Iowa
      Facial Growth Study were evaluated at ages 5, 10, 15, 25, and 45 years.
      Correlation coefficients were computed to determine the relationship between
      overbite and various skeletal parameters. Analysis of variance and Duncan's
      multiple-range test were used to compare various periods of growth. Statistical
      significance was predetermined at the 0.05 level of confidence. No significant
      correlations were found between the absolute values of overbite and the vertical
      skeletal parameters in either males or females. Incremental changes in overbite
      during four growth periods were compared with changes in various vertical
      parameters and only a few significant correlations were found. In males, the
      change in overbite was significantly correlated with changes in N-Ans'/N-Me and
      MP:SN during the 10-to-15 year growth period. In females, the change in overbite
      was significantly correlated with changes in N-Ans'/N-Me% during the 5-to-10-year
      period and also with change in Ar'-Go/S-Go% during the 15-to-25-year period. In
      general, changes in overbite with age are difficult to predict from the initial
      overbite in the deciduous or mixed dentitions. On the other hand, evaluation of
      individual curves shows that males who initially had the least amount of overbite
      maintained that trend during the later stages of development. Although overbite
      changes were significantly associated with changes in some vertical parameters,
      the associations were not of clinical significance for predictive purposes, and
      overbite changes are probably dependent on concurrent changes in the growth of
      the alveolar processes.

PMID- 9622758
TI  - Cephalometric effects of combined palatal expansion and facemask therapy on Class
      III malocclusion.
AB  - The purpose of this study was to examine the cephalometric changes that occur
      with palatal expansion/facemask therapy for Class III malocclusion. Pretreatment
      and posttreatment lateral cephalograms from 21 patients were traced and analyzed
      by traditional cephalometric measures, an x-y coordinate system, and along the
      functional occlusal plane. Differences between T1 and T2 values were analyzed
      with paired t-tests. Mean ages were 7.26 years (T1) and 8.18 years (T2). Average
      treatment time was 11.05 months. Statistically significant anterior movement of
      the maxilla occurred with increases in SNA (+2.35), maxillary depth (+2.22), and
      ANB (+3.66), and anterior movement of A-point (+3.34 mm) and ANS (+3.17 mm). The
      maxilla rotated counterclockwise, with PNS moving down more than ANS (-2.21 mm
      and -0.82, respectively). The mandible rotated clockwise with mild decreases in
      SNB (-1.32) and facial depth, (-1.2) but significant downward movement at menton
      (-4.34 mm). Occlusal plane analysis demonstrated that the correction was due more
      to the maxilla than the mandible (+2.35 and -1.88 mm, respectively). The
      maxillary molars moved forward (+1.70 mm) as did the incisors (+1.75 mm). Soft
      tissue changes included the nose and upper lip moving forward (3.43 and 3.67 mm,
      respectively), and menton moving downward (-3.49 mm). The results indicate that
      facemask/palatal expansion therapy improves Class III malocclusion by a
      combination of skeletal and dental changes that occur the anteroposterior
      dimension and in the vertical plane of space.

PMID- 9622759
TI  - Orthodontic maxillary expansion and its effect on nocturnal enuresis.
AB  - A previous retrospective study of 10 children with varying degrees of nocturnal
      enuresis has shown that one side effect of rapid maxillary expansion (RME) is
      spontaneous reduction in bed-wetting at night. The aim of this prospective study
      was to analyze the effect of RME treatment (mean 2 weeks) in cases of chronic,
      long-standing nocturnal enuresis. Ten children, 8 to 13 years old, who had not
      responded to conventional medical treatment for bed-wetting, were referred from
      the pediatric department. Within 1 month of RME of 3 to 5 mm, 4 children were
      completely dry and 3 showed notable improvement. The results are encouraging,
      especially given the spontaneous recovery rate of about 15% per year. A reduction
      in nocturnal enuresis in children has also been reported after tonsillectomy.
      However, in this pilot study, no significant associations could be found between
      improvement in nocturnal enuresis and improvement in the nasal airway, age,
      amount of expansion, or nasopharyngeal dimension (measured on cephalograms).

PMID- 9622760
TI  - Relationship between masticatory muscle activity and vertical craniofacial
      morphology.
AB  - The purpose of this study was to investigate the relationship between masticatory
      muscle activity during the day and vertical craniofacial morphology. The sample
      comprised 30 subjects (20 males and 10 females, age range 15 to 28 years, mean 24
      +/- 3.2 years) who had normal anteroposterior skeletal relationships and complete
      or nearly complete dentition without serious malocclusion or temporomandibular
      dysfunction. Using a portable electromyographic recording system, activities of
      the masseter, temporal, and digastric muscles were recorded for 3 hours during
      the day, excluding time spent eating, sleeping and exercising. A lateral
      cephalogram was taken of each subject with the teeth in occlusion. Activities of
      the masseter, temporal, and digastric muscles consisted mainly of low-amplitude
      bursts. The duration of digastric muscle activity was greater than that of either
      the masseter or temporal muscles. Masseter and digastric muscle activity was
      positively correlated. The activities of the masseter, temporal, and digastric
      muscles during the day consist of low-amplitude bursts and may be related to
      vertical craniofacial morphology.

PMID- 9622761
TI  - The effect of cross-sectional dimensional variations of square and rectangular
      chrome-cobalt archwires on torsion.
AB  - The purpose of this investigation was to study the control of cross-sectional
      dimensions and edge bevel by various manufacturers in the production of chrome
      cobalt archwires and this effect on transmitting torque through an .018 inc slot
      bracket system. Twenty-seven different square and rectangular chrome-cobalt wires
      commonly used in the edgewise technique supplied by five different manufacturers
      were studied with respect to dimensions, edge bevel, and mechanical properties in
      torsion. The mechanical study simulated application of torque to an individual
      tooth. Standard brackets with .018 inch slot heights were used. The results show
      that variation in cross-sectional dimension and edge bevel leads to variable
      torsional play (third-order clearance). As an example, .016 x .016 wires have a
      mean torsional play of as much as 26.8 degrees, with a range of 21.0 to 32.3
      degrees. When using .016 x .016 wires, one must apply from 34.8 to 48.6 degrees
      of twist to get 20 N-mm of torsional moment. This variation is primarily due to
      the rather wide range in torsional play. As a result, the prediction by which a
      predetermined torsional moment can be delivered becomes uncertain. The results
      also show that because the working range in torsion of chrome-cobalt wires is
      somewhat limited due to high torsional stiffness, precise delivery of torsional
      moment based on the condition present in the oral cavity is difficult. The
      torsional stiffness varies between manufacturers within the various dimensional
      groups as a result of differences in cross-sectional geometry and material
      properties.

PMID- 9622762
TI  - Effects of a myofunctional appliance on orofacial muscle activity and structures.
AB  - The aim of the study was to examine the effect of an oral shield treatment on
      orofacial muscle activity and facial morphology in children with lip and/or
      tongue dysfunction. The sample consisted of 7 girls and 2 boys, 7 to 12 years
      old. EMG recordings with and without the shield in situ were obtained when the
      shield was placed, and 3, 6, and 12 months later. Lateral cephalograms were
      obtained at the initial and 1-year stages. The lip muscles showed dominant
      activity when the subjects were sucking on an empty straw and during swallowing;
      this was strongest during the first 3 months. The mentalis, buccinator, and
      digastric muscles generally showed weaker activity. The anterior temporal muscle
      showed dominant activity during maximal clench, but after the 3-month stage a
      significant decrease was noted. After 1 year of treatment, no significant changes
      in overjet or overbite were observed. Most of the craniofacial growth changes
      were normal for the age group. The results indicate that treatment with an oral
      shield caused a decrease in orofacial muscle activity during oral functions.
      Although there was a slight average retraction of the maxillary incisors, the
      change in position was not statistically significant.

PMID- 9622763
TI  - Effects of local administration of osteocalcin on experimental tooth movement.
AB  - The purpose of this study was to evaluate the effects of local administration of
      osteocalcin, a major noncollagenous bone matrix protein, on experimental tooth
      movement in rats. An orthodontic elastic band was inserted between the upper
      first and second molars, and the first molar was moved mesially. Purified
      osteocalcin (0 to 10 micrograms) in 20 microliters of phosphate-buffered saline
      was injected into the region of the root bifurcation of the first molar daily for
      4 days. Tooth movement increased significantly following the injections.
      Histological studies revealed that the injections markedly stimulated the
      appearance of osteoclasts on the pressured side of the alveolar bone surface. The
      results suggest that osteocalcin has an additive effect on the rate of
      orthodontic tooth movement through the enhancement of osteoclastogenesis on the
      pressured side.

PMID- 9622764
TI  - A controlled study of associated dental anomalies.
AB  - The purpose of this study was to reveal patterns of association among seven types
      of dental anomalies (aplasia of second premolars, small size of maxillary lateral
      incisors, infraocclusion of primary molars, enamel hypoplasia, ectopic eruption
      of first molars, supernumerary teeth, and palatal displacement of maxillary
      canines) in an untreated orthodontic population, ages 7 to 14. The prevalence of
      associated tooth anomalies in seven groups of 100 subjects selected according to
      one primarily diagnosed dental anomaly was compared with the prevalence of the
      examined dental anomalies in a control group of 1,000 subjects. Significant
      reciprocal associations (p < 0.005) were found among five of the anomalies
      (aplasia of second premolars, small size of maxillary lateral incisors,
      infraocclusion of primary molars, enamel hypoplasia, and palatal displacement of
      maxillary canines), suggesting a common genetic origin for these conditions.
      Supernumerary teeth appeared to be a separate etiological entity with respect to
      all other examined tooth anomalies. The existence of associations between
      different tooth anomalies is clinically relevant, as the early diagnosis of one
      anomaly may indicate an increased risk for others.

PMID- 9622765
TI  - Case report: Class II correction using a modified Wilson bimetric distalizing
      arch and maxillary second molar extraction.

PMID- 9622766
TI  - Case report: orthodontic treatment of dental problems in incontinentia pigmenti.
AB  - Incontinentia pigmenti is an uncommon genodermatosis that occurs in female
      infants. The characteristic dental defects are partial anodontia and the presence
      of some peg-shaped teeth. This report describes a patient with incontinentia
      pigmenti who exhibited multiple missing teeth in both arches. The patient had
      malpositioned teeth and decreased occlusal vertical dimension associated with the
      missing teeth. Orthodontic treatment was required for prosthetic purposes. The
      dental anomalies of incontinentia pigmenti and the treatment procedure are
      presented.

PMID- 9622767
TI  - An enzymatic assay for erythrocyte creatine as an index of the erythrocyte life
      time.
AB  - OBJECTIVES: To establish and estimate an enzymatic measurement of creatine in
      erythrocytes as an index of the erythrocyte life time. DESIGN AND METHOD: The
      measurement of creatine in erythrocytes was performed using an enzymatic assay
      kit that was developed for serum and urine creatine. An erythrocyte sample was
      subjected to creatine measurement after hemolysis and deproteinization.
      Performance of the method for creatine measurement in erythrocytes was estimated.
      Effects of age and gender on the creatine content of erythrocytes were also
      estimated in 305 normal subjects. RESULTS: The method showed within-run CVs
      varying from 0.7 to 1.0% (n = 20), and between-day CVs from 1.3 to 1.7% (15
      days). Good linearity was observed at least up to 1000 mumol/L as creatine value
      in hemolyzed sample. The analytical recovery was calculated to be 98.1 +/- 1.3%
      on average. No considerable interference by various substances, including
      guanidino compounds and amino acids, with the assay was observed. Excellent
      correlation was observed between the present method and high performance liquid
      chromatography. With the unit of mumol/g Hb: slope, 1.034 +/- 0.003 (mean +/-
      SD); intercept, -0.059 +/- 0.012 (mean +/- SD); correlation coefficient, 0.9996;
      and Sy.x, 0.069. With the unit of mumol/L RBC: slope, 1.033 +/- 0.003 (mean +/-
      SD); intercept, -18.23 +/- 3.55 (mean +/- SD); correlation coefficient 0.9996;
      and Sy.x, 20.40. A significant increase in erythrocyte creatine was observed in
      females aged 11- to 50 years old as compared with males in the corresponding age
      bracket, however, a gender difference was not observed in other age bracket. This
      finding suggests the possibility of a slight decrease in the erythrocyte life
      time due to menstruation in females. CONCLUSION: This study showed that the
      present method is favorable for quantifying erythrocyte creatine, and has
      analytical characteristics suitable for routine work in clinical laboratories.

PMID- 9622768
TI  - Laboratory and clinical evaluation of two glucose meters for the neonatal
      intensive care unit.
AB  - OBJECTIVE: To evaluate the analytical and clinical performance of the One Touch
      II and Advantage glucose meters for use in neonatal specimens. DESIGN AND
      METHODS: For the laboratory evaluation, a total of 96 umbilical cord whole blood
      specimens were analyzed on the One Touch II and/or Advantage meters. Samples were
      centrifuged after analysis on the meters and plasma glucose was determined on the
      Hitachi 917. For the clinical evaluation, a total of 64 infants had specimens
      analyzed on each of the meters as well as on the laboratory analyzer. RESULTS: In
      the laboratory and clinical evaluations, both meters correlated well (r > 0.9, p
      < 0.001) with the plasma values for the Hitachi 917. However, the mean difference
      between the Advantage and Hitachi 917 was lower than that of the One Touch II in
      both the laboratory (-0.23 vs -0.64 mmol/L) and the clinical evaluations (-0.08
      vs -0.60 mmol/L). 53.1% of One Touch and 26.6% of Advantage results from the
      clinical study had a discrepancy of > 0.5 mmol/L from the laboratory value.
      CONCLUSIONS: For neonatal specimens, glucose meters must have good low end
      precision, sensitivity and accuracy, In this study, the Advantage meter had fewer
      discordant results and better correlation with the Hitachi 917. Overall, nursing
      and laboratory staff preferred the performance and characteristics of the
      Advantage meter.

PMID- 9622769
TI  - Morphological changes of human erythrocytes induced by cholesterol sulphate.
AB  - OBJECTIVES: Morphological alterations of human erythrocytes induced by
      cholesterol sulphate (5-cholesten-3 beta-ol sulphate, CS) were studied. DESIGN
      AND METHODS: Influence of CS on red blood cell stability (in isotonic conditions)
      by simultaneous application of flow cytometry and scanning electron microscopy
      was studied. RESULTS: In isotonic medium CS induces erythrocyte size and shape
      changes in dose-and time-dependent manner. Incubation (in vitro) of erythrocytes
      with CS concentrations from 4 x 10(-5) mol/dm3 to 8 x 10(-5) mol/dm3 led to a
      progressive sphero-echinocitic shape transformation accompanied by a cell size
      decrease. In contrast to this, for CS content equal to 1 x 10(-5) mol/dm3 the
      maintenance of the normal biconcave shape of red blood cells was observed.
      CONCLUSIONS: The results suggest that CS, similarly to numerous evaginating
      amphiphilic agents, induces a transformation of the erythrocyte normal discoid
      shape to echinocytic form. This effect may be caused, at least partly, by an
      asymmetric expansion of the membrane lipid bilayer due to asymmetric distribution
      of CS incorporated into the membrane. The echinocytic shape transformation of
      erythrocytes indicated that CS intercalates in the outer hemileaflet of the lipid
      bilayer leading to membrane externalization.

PMID- 9622770
TI  - Evaluation of the analytical performance of the Boehringer Mannheim Elecsys 2010
      immunoanalyzer.
AB  - OBJECTIVES: We evaluated the analytical performance of the Elecsys 2010
      immunoanalyzer (Boehringer Mannheim Canada), which is based on a new detection
      technology, electrochemical luminescence. DESIGN AND METHODS: We used six
      representative assays from the initial launch menu of the instrument: thyroid
      stimulating hormone (TSH), free thyroxine (FT4), troponin T, human chorionic
      gonadotropin (hCG), carcinoembryonic antigen (CEA), and prostate specific antigen
      (PSA). Within-run and between-day imprecision were evaluated using pools of human
      specimens at low, mid and high concentrations. Linearity was evaluated by
      diluting specimens with high analyte concentrations with specimens that had a low
      level of this analyte. Carry over and hook effect were investigated using
      specimens with high concentrations of hCG. Functional sensitivity was studied by
      running low TSH specimens over 21 daily runs, and by comparing the scatterplot of
      FT4 as a function of TSH. Over 100 specimens distributed across the analytical
      range were analyzed with two comparison methods: ES 300 (Boehringer Mannheim
      Canada) and AxSYM (Abbott Laboratories). RESULTS: Within-run and between-day
      imprecisions were less than 4% and 10%, respectively, for most assays. All assays
      were linear over the whole analytical range. Carry over was minimal (< 0.0002%).
      A hook effect was present for hCG levels greater than 560,000 U/L. The functional
      sensitivity of the TSH assay was lower than 0.02 mlU/L. Correlation coefficients
      were all > 0.94. Small proportional errors were observed in comparison studies
      for the CEA and PSA assays. CONCLUSIONS: The Elecsys 2010 system was shown to
      have an acceptable analytical performance for the rapid analysis of a wide
      variety of analytes. The hook effect observed with hCG assay would imply that the
      laboratory informs the clinicians of the possibility of falsely low values in
      trophoblastic diseases or that all specimens with values greater than 3000 U/L
      are reassayed after dilution.

PMID- 9622771
TI  - Comparison of the Ames, Randox and Roche methods with the Synermed method for the
      determination of serum iron concentrations on nondialysis and dialysis specimens.
AB  - OBJECTIVES: To evaluate the Ames, Randox, Roche, and Synermed methods for the
      measurement of serum iron and to investigate patterns of possibly discrepant
      results in dialysis patients. METHODS: Assays were performed on the Cobas Fara II
      analyzer. Precision and accuracy studies were conducted; recovery studies were
      done by adding pooled serum from dialysis patients to an assayed human serum
      based control. Patient comparisons included over 150 nondialysis patients and 30
      dialysis patients. RESULTS: For the Ames, Randox, Roche and Synermed methods, the
      between-run precision was less than 2.80% with the normal aqueous iron standard;
      2.00, 2.70, 0.80, and 2.00% for the four methods with the high serum iron
      control, respectively, and less than 2.30% with the serum pool. Using a pooled
      serum from dialysis patients, between-run precision was higher with all four
      methods. With an abnormal assayed human serum-based control, accuracy was over
      98% for the four methods. Recoveries were 121% for the Ames and Randox methods
      and 104-105% for the Roche and Synermed methods. Accuracy as assessed with Murex
      EQAS specimens ranged from 71 to 80%, 71 to 96%, 98 to 99.5%, and 42 to 50% for
      the four methods, respectively. For comparisons of the Ames, Randox, and Roche
      methods with the Synermed method, difference analyses revealed biases (SD) for
      nondialysis patients of 1.9 (2.7), 1.5 (3.3), and 1.8 (2.2) mumol/L,
      respectively; and for dialysis patients of 8.2 (13.3), 5.1 (5.4), and 1.4 (1.7)
      mumol/L. Standard linear regression analyses and correlation coefficients are
      also provided. CONCLUSIONS: The Roche method was slightly more precise than the
      other methods. Using an abnormal assayed serum-based control, all methods showed
      good accuracy. Recovery studies with pooled serum from dialysis patients showed
      interferences with the Ames and Randox methods and good recovery with the Roche
      and Synermed methods. With the bovine serum-based Murex samples, all but the
      Roche method yielded some low results; the Synermed method has been reported to
      suffer from matrix problems with bovine serum albumin. Based on recovery studies
      and difference analyses, the Ames and Randox methods revealed discrepancies in
      iron results for samples from dialysis patients. The Roche and Synermed methods
      appeared to be suitable for measurement of serum iron in dialysis patients.

PMID- 9622772
TI  - Relation of a common mutation in methylenetetrahydrofolate reductase to plasma
      homocysteine and early onset coronary artery disease.
AB  - OBJECTIVE: In the presence of low serum folate, mutant 5,20
      methylenetetrahydrofolate reductase (MTHFR + [A223V/C677T]) in the homozygous
      state (+/+), may predispose to higher plasma homocysteine (tHct) levels and
      coronary artery disease (CAD). To determine the impact of this relationship on
      predisposition to early-onset CAD, we examined the prevalence of the mutation and
      plasma tHct in patients with early-onset CAD and compared them to patients
      manifesting CAD later in life. METHODS: Three hundred patients with history of
      acute myocardial infarction or angina pectoris and angiographically documented
      CAD were studied. Patients consisted of two groups: group 1 (G1 = 150 patients)
      presenting with these findings under age 50; while group 2 (G2 = 150) presented
      for the first time over age 65 years. Prevalence of the MTHFR+ mutation was
      assessed by molecular analysis, and plasma tHct and folate were measured. An
      association of the +/+ genotype with early onset CAD could lead to its higher
      prevalence in the younger age group. RESULTS: There was no significant difference
      in the frequency of the (+/+) genotype between the two groups (G1: 11.3% vs. G2:
      11.3%). However, patients with the (+/+) genotype in both groups had higher tHct
      when plasma folate was below the mean value (G1: p < 0.0001 while G2: p < 0.01).
      CONCLUSION: The mutant MTHFR genotype was not found to be a determining factor in
      early-onset CAD. Higher tHct values were obtained in the older age group, which
      is expected because other studies have shown that tHct levels increase with age.
      A significant relation was shown between MTHFR genotype and low folate status
      yielding high tHct levels in those with the (+/+) genotype. As this relation was
      seen in both groups, although to a lesser extent in the older G2, it does not
      explain the underlying cause of early-onset CAD.

PMID- 9622773
TI  - Surgical trauma induces group II phospholipase A2 production by neutrophils at a
      local site after surgery.
AB  - OBJECTIVES: Group II phospholipase A2 (PLA2) regulates eicosanoids and platelet
      activating factor (PAF) production and plays an important role in regulating
      critical mediators in inflammatory diseases such as trauma, sepsis and multiple
      organ failure. To elucidate the local effect of surgical trauma, we investigated
      the production of group II PLA2 at a local site after surgery. DESIGN AND
      METHODS: We utilized a radioimmunoassay to measure group II PLA2 levels in
      peritoneal exudates from the operative field and blood in patients who underwent
      gastrectomy. We also investigated the production of group II PLA2 in cells from
      peritoneal exudates by Northern blotting and immunocytochemistry. RESULTS:
      Immunoreactive group II PLA2 levels were significantly increased from 3 h after
      surgery and peaked at 12 h peritoneal exudates. However, serum group II PLA2
      levels peaked at 24-48 h and decreased gradually after surgery, findings similar
      to levels of postoperative serum C-reactive protein (CRP). There was no
      significant correlation between group II PLA2 levels in peritoneal exudates and
      those in blood. Group II PLA2 mRNA was expressed at high level in cells from
      peritoneal exudates, by Northern blot analysis, but not those from blood. The
      localization of group II PLA2 protein was intense in neutrophils, as determined
      by immunocytochemistry. No group II PLA2 expression was observed in corresponding
      peripheral blood cells. CONCLUSIONS: After surgery, group II PLA2 is increased in
      peritoneal exudates prior to elevation in the blood circulation and is produced
      by neutrophils recruited and activated at a local site. Group II PLA2 produced in
      peritoneal exudates by neutrophils has an important role in the physiological and
      pathological states at a local site, after surgery.

PMID- 9622774
TI  - Effect of septic shock on nitrate, free amino acids, and urea in murine plasma
      and urine.
AB  - OBJECTIVES: Concentration changes of free amino acids, urea and nitrate in plasma
      and urine were studied for the murine model of septic shock. METHODS: After
      administration of a bolus dose of bacterial lipopolysaccharide (LPS),
      concentrations of amino acids and urea in plasma, and urea and nitrate in urine
      were determined. RESULTS: For individual amino acids four different trends were
      observed: (1) no change ( e.g., taurine, histidine, phenylalanine,
      hydroxproline); (2) continuous increase (e.g., aspartate and glutamate); (3)
      continuous decrease (e.g., threonine, serine, asparagine, proline, methionine,
      tyrosine); and (4) decrease during the first 4 hours, but return to normal at 8
      hours after the LPS treatment (e.g., all the other amino acids). The ratio of
      phenylalanine to tyrosine was increased to about 2x. In plasma, urea
      concentration was increased about 3x, but in urine it decreased about 4x. Nitrate
      levels were increased 3x in urine. CONCLUSION: These early changes in the
      concentrations of amino acids as well as in the urea and nitrate may be useful as
      sensitive markers for the early and rapid diagnosis of septic shock.

PMID- 9622776
TI  - Spuriously high free thyroxine with the Access free T4 assay.

PMID- 9622775
TI  - Increased retinol binding protein in the sera of patients with severe ischemic
      damage of the liver after transplantation.
AB  - OBJECTIVE: To study retinol binding protein variation in the serum of patients
      who have undergone liver transplantation. METHODS: Retinol binding protein was
      retrospectively determined by the immunonephelometric method on serum from 14
      patients who had undergone orthotopic liver transplantation 2 weeks after the
      surgery and then once a month during the first year posttransplantation. The
      patients were divided into two groups on the basis of early (first 10 days)
      postoperative graft function: group I, 6 patients with severe ischemic damage;
      and II 8 patients with moderate-severe liver dysfunction. RESULTS: The men
      retinol binding protein level at one year of follow-up was persistently higher in
      group I than in group II (83.1 +/- 33.4 vs 44.6 +/- 20.7 mg/L, p < 0.001).
      Interestingly, retinol binding protein levels remained higher in patients of
      group I event when the other biochemical parameter of liver function returned to
      normal. The increase in retinol binding protein serum levels was independent of
      variation in other parameters of liver and kidney function, but was correlated
      with an increase in transthyretin and retinol levels. CONCLUSION: Our results
      show a close relationship between a permanent high retinol binding protein level
      and severe graft injury after liver transplantation. However, the mechanism
      underlying the increase remains to be defined.

PMID- 9622777
TI  - Father by law: effects of joint legal custody on nonresident fathers' involvement
      with children.
AB  - Family membership and household composition do not always coincide. Joint legal
      custody after divorce formalizes the relationship between fathers and children
      who live apart. Policymakers hope that explicit acknowledgment of nonresident
      fathers' rights and responsibilities will increase their involvement with their
      children. I use prospective data from the National Survey of Families and
      Households to examine the association between joint legal custody and two aspects
      of nonresident fathers' contributions to their children--the frequency of visits
      between fathers and children and child-support payments. The analysis examines
      approximately 160 families in which parents divorced between interviews conducted
      for Wave 1 (1987-1988) and Wave 2 (1992-1994) of the survey. I investigate the
      effects of joint legal custody holding constant physical custody or replacement
      by restricting the analysis to children who live with their mothers most of the
      year. Controlling for socioeconomic status and the quality of family
      relationships before separation, fathers with joint legal custody see their
      children more frequently and have more overnight visits than do other fathers.
      The positive effect of joint legal custody on frequency of visits persists once
      unobserved differences among families are taken into account. Although fathers
      with joint legal custody pay more child support than those without joint legal
      custody, this difference lacks statistical significance when other family
      characteristics are taken into account. These findings support the view that
      joint legal custody may encourage some aspects of paternal involvement after
      divorce.

PMID- 9622778
TI  - Who gets custody?
AB  - Changes in the living arrangements of children have implications for social
      policy and children's well-being. Understanding who gets custody on divorce-
      mother, father, or both sharing custody--can also inform our understanding of
      family organization and the merits of alternative theories of marriage and
      divorce. We examine physical-custody outcomes among recent Wisconsin divorces in
      an effort to understand the factors associated with shared custody as well as
      mother-sole custody and father-sole custody. Although mother-sole custody remains
      the dominant arrangement, shared custody has increased over a nine-year period.
      We find that the probability of shared custody increases with parent's income.
      Prior marital history, parents' ages, the age and gender of children, and the
      legal process also have an impact on the probability of shared custody. In
      contrast to shared custody, the probability of father-sole custody decreases with
      parent's income, while the relationship with other significant factors is
      generally similar. The notable exception is that, unlike shared custody, we find
      no evidence for an increase over time in the probability of father-sole custody.
      We also find that when the father has a higher proportion of the couple's total
      income, both shared custody and father-sole custody are more likely.

PMID- 9622779
TI  - The impact of child support on cognitive outcomes of young children.
AB  - We use the National Longitudinal Survey of Youth-Child data to address three
      questions. First, does the receipt of child support have beneficial effects for
      children with absent fathers apart from increasing income? Second, do the effects
      of child support differ when child-support awards and payments are made
      cooperatively as opposed to being court ordered? Third, are any positive effects
      of child support solely a product of unmeasured differences among fathers and
      families? Controlling for the socioeconomic characteristics of the child and
      family, we find some evidence that receipt of child support has a positive impact
      on children's cognitive test scores over and above its contribution to total
      income. However, the effects vary by test, by race, and by reason for father's
      absence. Our results also indicate that the distinction between cooperative and
      noncooperative awards is important. Finally, our instrumental variables estimates
      show that the effects of child support persist after we control for unobserved
      characteristics of fathers and families.

PMID- 9622780
TI  - Young unwed fathers of AFDC children: do they provide support?
AB  - We examine the support provided by fathers of children born to disadvantaged
      teenage mothers. Our sample includes the fathers of 6,009 children born over a
      two-year period to 3,855 teenage mothers receiving AFDC in three economically
      depressed inner cities. These fathers provide little social and economic support
      to their children. Support declines as their children age from infants to
      toddlers and as fathers' relationships with the mothers grow more distant.
      Fathers' employment status and educational attainment positively affect the
      amount of economic support that they provide but do not strongly influence the
      amount of social support they provide.

PMID- 9622781
TI  - Parenting from a distance: the effects of paternal characteristics on contact
      between nonresidential fathers and their children.
AB  - Changes in marital and fertility behavior have influenced the role of father for
      many men. We use data from the first two waves of the National Survey of Families
      and Households to examine various sociodemographic, situational, and attitudinal
      characteristics that might influence the degree of contact between nonresidential
      fathers and their minor children. We tap two different dimensions of distance
      parenting and find that although several variables influence both visiting and
      talking on the telephone or writing letters, some factors (the presence of
      multiple children in a household) predict visiting only, while others (child's
      age and gender) predict only verbal/written contact. Similarly, some of the life
      course decisions made by fathers appear to crowd out their involvement with
      nonresidential children, whereas other decisions reinforce their parenting
      behavior.

PMID- 9622782
TI  - Paternal involvement with adolescents in intact families: the influence of
      fathers over the life course.
AB  - We measure the quality and quantity of fathers' involvement with adolescent
      children in intact families over time using longitudinal data from The National
      Survey of Children. We examine differentials in fathers' involvement by
      children's and family characteristics and model the long-term effects of fathers'
      involvement on children's outcomes in the transition to adulthood. Fathers are
      more involved with sons than with daughters and they disengage from adolescents
      with increasing marital conflict. We find beneficial effects for children of
      father's involvement in three domains: educational and economic attainment,
      delinquent behavior, and psychological well-being. The course of affective
      relations throughout adolescence also has a beneficial effect on delinquent
      behavior and psychological well-being.

PMID- 9622783
TI  - Fathers and absent fathers: sociodemographic similarities in Britain and the
      United States.
AB  - Using data from the British Household Panel Survey and the National Survey of
      Families and Households in the United States, we present a sociodemographic
      profile of fathers and compare the determinants of absent fatherhood in each
      country. Although fatherhood has a younger profile in the United States,
      especially for blacks, predictors of fathers' residency with their children are
      remarkably similar in the two countries. In both countries, the strongest
      predictor of a father's absence is the parent's relationship to each other at the
      time of the child's birth. Policy implications of this finding are discussed.

PMID- 9622784
TI  - Men matter: additive and interactive gendered preferences and reproductive
      behavior in Kenya.
AB  - The extent of men's roles in reproductive decision-making in Africa is a subject
      of contention. Despite the volume of work on the roles men play in fertility
      decisions, there have been few attempts to derive direct empirical estimates of
      the effect of men's preferences on reproductive behavior. I employ 1989 and 1993
      Kenya Demographic and Health Surveys to examine the relative roles of the
      reproductive preferences of males and females on contraceptive use. Additive and
      interactive measures of preferences document a significant effect of men's
      preferences, which may eclipse women's preferences. The implications of these
      findings are discussed.

PMID- 9622785
TI  - Work, income, the economy, and married fathers as child-care providers.
AB  - Previous research on fathers as child-care providers indicates a need to study
      the father's role in child care in the context of different economic cycles.
      Using data from the 1988, 1991, and 1993 panels of the Survey of Income and
      Program Participation, we examine whether fathers' availability and the couple's
      economic resources are differently related to child care by fathers over time. We
      focus on the differences between 1991--a recession year--and 1988 and 1993--two
      nonrecession years. Increased availability of fathers is significantly related to
      higher levels of fathers' participation in child care in all three years.
      Relative economic resources between husbands and wives help explain care by
      fathers only during the recession year, whereas family income is important only
      in the nonrecession years. These results suggest that in the future, researchers
      should acknowledge fluctuations in the economy when studying husbands'
      participation in traditional female tasks, as macroeconomic shifts appear to
      impact the likelihood of married fathers caring for their preschoolers during
      mothers' working hours.

PMID- 9622786
TI  - Have African American men become less committed to marriage? Explaining the
      twentieth century racial cross-over in men's marriage timing.
AB  - Prior to World War II, the median age at marriage for white men was later than
      that for African American men. Since World War II, African American men have, on
      average, married later than white men. A discrete-time hazard model using data
      from the National Survey of Families and Households was analyzed to explain this
      racial cross-over in men's timing of marriage. Dramatic increases in the
      educational attainment of African American parents and the large movement of
      African Americans out of the South brought about the racial cross-over in the
      timing of marriage. Increased enrollment in higher education among African
      American men also contributed to the racial cross-over in the timing of marriage.
      Although lack of full-time employment and military service delayed marriage,
      these factors did not contribute to the racial cross-over.

PMID- 9622787
TI  - [Cost of illness: an inextricable maze or an aid in decision making? The case of
      schizophrenia].
AB  - The cost of schizophrenia has been a major point of interest abroad. In the
      United States, two authors evaluated the direct cost of the illness. According to
      Gunderson and Mosher (13), it reaches US $25,625 million. In the United Kingdom,
      the estimations are of 390 million pounds (7) and 1,178 million pounds (16). In
      Australia, a direct cost calculation based on incidence leads to US $24,621
      million (1), which is 6 times as much as the cost of infarction. At last, the
      only French study (Rouillon et al., 1997) gives a result of FF 17,911 millions.
      The indirect cost estimations vary from 71% (29) to 83% (13) of the total cost.
      The difference between the 6 publications are suprizing (especially when they
      concern the same country) and are probably link to the difference of methodology.
      This point tempers largely the interest of these studies as a tool in order to
      hierarchise Public Health priorities. Moreover, the elaboration of structures
      equivalencies between the different countries is an ambitious enterprise and make
      difficult comparisons of the studies. Finally, the lack of transparency of some
      of them limits their credibility.

PMID- 9622788
TI  - [Survey of the quality of prescribing anticholinergic drugs in neuroleptic
      treated patients].
AB  - AIMS: A retrospective survey of prescription of anticholinergic drugs to patients
      treated with antipsychotics (i.e. neuroleptics) was set up in order to evaluate
      quality and adequation of medical care. This study was meant as a first step of a
      therapeutic audit, aimed at improving clinical practices and attitudes. METHODS:
      This retrospective study was conducted concomitantly at three different
      psychiatric institutions, jointly at each site by a senior psychiatrist and a
      senior pharmacist and at two different dates, six months apart one from the
      other. In a first step, references for therapeutic practice were collected, from
      current scientific literature, protocols and professional practices. Seven
      criteria were selected. Each criterion consisted in a variable, an expected
      standard, an observed standard and exceptions. Information was collected from the
      clinical charts and prescriptions of 67 patients (33 men, 34 women), aged 47.8 +/
      14.9 years (range 21-76 years), treated with anticholinergic and neuroleptic
      drugs. These data were then analyzed, according to the seven predefined criteria
      and the observed standards matched with the expected ones. RESULTS: Depending on
      the criterion, important variations could be observed, the observed standards
      ranging from 100% to 11.9% of the expected standards.

PMID- 9622789
TI  - [Social Autonomy Scale. First validation data].
AB  - The Assessment of Social Self-Sufficiency (ASSS) is a scale of hetero-assessment,
      made up of seventeen items and five subsets, devised to investigate the self
      sufficiency level of the persons who suffer from chronic psychiatric trouble. We
      know indeed that, for these patients, the success of their rehabilitation plans
      depends on their ability to face up to tangible problems in everyday life. This
      publication expounds the first work validating the ASSS. The "intercotators"
      accuracy of the work, its sensitiveness, its concurrent validity investigated
      with regard to the Global Assessment of Functioning Scale (GAF of the DSM III-R)
      as well as the inner contents seem to be very satisfactory.

PMID- 9622790
TI  - [Anxiety disorders in general practice: frequency--treatment. A survey of the
      Aquitaine Sentinel Network].
AB  - OBJECTIVE: This study, conducted in Aquitaine (Southwest France), was designed to
      assess both frequency and treatment of anxiety disorders in general practice
      patients. METHOD: The assessment was cross-sectional; a random sample of 312
      patients was chosen and evaluated during the last week of Mai 1993, by 55 general
      practitioners who usually collaborate in the Aquitaine Sentinel Network,
      supported by the Department of Medical Statistics and Public Health of the
      University of Bordeaux. Anxiety disorders were assessed by the Composite
      International Diagnostic Interview and level of depression was self evaluated by
      the Beck Depression Inventory. The physicians reported current psychological and
      psychopharmacological treatments, and request for treatment of every patient
      tested. RESULTS: Frequency of anxiety disorders is concordant with available
      epidemiological data in French general population. There is no sex difference for
      anxiety disorders in this study, in opposition to what is known in the general
      population (2 = 1.47, p > .05). Women are more treated than men (drugs: chi(2) =
      7.31 p < .01; psychotherapies: chi(2) = 7.58 p < .04) although they don't request
      for more treatment (chi(2) = .59 p M .05). Benzodiazepines and psychodynamic
      oriented therapies are the most used treatments for any anxiety disorders;
      specific treatments (antidepressive drugs, behavioral therapies) of anxiety are
      very rarely prescribed. CONCLUSION: This study shows the difference between the
      current theoretical knowledge in anxiety disorders, and the management of these
      disorders by the general practitioner. It suggests that patient's request, in
      opposition to what is often found in the literature, is not a determinant factor
      in treatment.

PMID- 9622791
TI  - [Environmental and psychosocial aspects of genetic research in psychiatry].
AB  - Psychiatric disorders are thought to arise as a result of interactions between
      genetic vulnerability and environmental risk factors. However, research methods
      to actually investigate the pattern of hypothesized interactions have only
      recently been developed. In this article, we review the evidence that genes
      increase the risk for psychosis by making individuals more sensitive to
      environmental risk factors (genotype-environment interaction), or by making
      individuals more likely to select high-risk environments (genotype-environment
      correlation). It is likely that at least some of the impact of genes on the
      occurrence of psychosis is mediated through (sensitivity for ) environmental risk
      factors such as a dysfunctional early family rearing environment, paternal
      absence, use of cannabis, complications of birth and pregnancy, stressful life
      events and unknown environmental risk factors associated with urban life and
      membership of certain ethnic groups. With the advent of molecular genetics,
      further knowledge about possible genotype-environment interactions is urgently
      required in order to develop and improve strategies for the prevention and early
      treatment of psychosis.

PMID- 9622792
TI  - [Hormone treatment of sex offenses].
AB  - In humans, roles for androgens have been described in the regulation of
      sexuality, aggression, cognition, emotion and personality. Recent advance in the
      understanding of factors that are associated with sexual aggression have led to
      improved methods of treatment. A number of organic treatments which reduce the
      plasma testosterone levels or decrease androgen effects on target cells are
      available. These treatments may reduce the chance of reoffending of sexually
      aggressive men. The authors will review the literature on orchidectomy,
      oestrogens or progestogens such as medroxyprogesterone acetate (MPA) or
      cyproterone acetate (CPA) which are currently used in the treatment of deviant
      sexuality. From now, orchidectomy and treatment with either estrogens or MPA are
      withdrawn. The authors will also report the good clinical efficacy of a GnRH
      analogue (triptoreline) in eleven sex offenders. When used in conjunction with
      psychotherapy, they may benefit sex offenders especially in those who are
      motivated for treatment.

PMID- 9622793
TI  - Cognitive impairment in depressive disorders. Neuropsychological evaluation of
      memory and behavioural disturbances.
AB  - The purpose of this article is to discuss the contribution that clinical
      neuropsychology and neuropsychological assessment can conter to neuropsychiatry,
      particularly in the evaluation of cognitive disturbances and pharmacological
      treatment of depression. Six patients (4 females, 2 males; age: 16-54 years old)
      suffering from depressive disorders underwent a clinical neuropsychological
      examination. Depending on the memory scores obtained on the Rey-Osterrieth
      complex figure test, the patients were classified as having mild or no memory
      impairment (< 20% decrease), moderate memory impairment (20-40% decrease) or
      severe memory alteration (> 60% deterioration). Evaluation of memory scores of
      two other memory tests (Wechsler memory scale and Rey visual design learning
      test) were also considered. Patients who were classified as having severe memory
      impairment were consistently reported as seriously impaired on all memory tests.
      The severity of cognitive dysfunction is in accordance with the serious ness of
      the neuropsychiatric disturbances of the patients as revealed by personality
      testing (MMPI, IDS and Eysenck questionnaires) or by personal details as assessed
      during the interview. This paper discusses the importance of the utility of a
      comprehensive neuropsychological evaluation of depressed patients and seriously
      considers the possibility of the use of this approach for pharmacological
      treatment evaluation.

PMID- 9622794
TI  - [Cultural assimilation and factitious symptoms].
AB  - With description of the case of a patient birth in Maroco and emigrated in France
      at 10 years old, met during 6 years, we try to include signs noticed in a
      nosologic entity. Some patients offer many complaints and have very frequent
      contacts for themselves or their family, with the practitioners. Events of
      current life grow expression of their troubles. Cultural difference will be
      integrated in anamnesis, hearing and in care. Production of symptoms for himself
      or for children are called: factitious disorders, Munchhausen's syndrome, Polle's
      syndrome or Meadow's syndrome. Generally physicians are in check with these
      patients. During medical session this relationship requires to try to have
      clarifications or have research of meaning. These patients are very often
      refractory in psychotherapy and no compliant for institutional therapy. For
      second generation of immigrants, cultural identity is in conflict with personal
      identity, in part caused by the decay of social group of belonging. Troubles
      caused by distortion of fusional relation with mother can be favoring factors of
      these diseases for Maghrebian patients.

PMID- 9622795
TI  - [Effect of sertraline on blood clozapine].

PMID- 9622796
TI  - Laminar organization of neuronal activities in area 8 of rhesus monkeys during a
      symmetrically reinforced visual GO/NO-GO task.
AB  - An attempt was made to clarify the laminar distributions of neurons activated
      during a symmetrically reinforced, visually guided GO/NO-GO task with visual cues
      for which Brodmann's area 8 (Walker, 1940) is considered an essential region (cf.
      Petrides, 1986). We systematically recorded single unit activities in area 8 in
      200 microns steps from the surface to the bottom of the cortex, using a glass
      coated microelectrode that contained a carbon fiber. The GO/NO-GO task consisted
      of four periods in sequence: an intertrial interval (ITI; waiting period, warning
      period (which started with a warning cue), GO/NO-GO period (which started with a
      GO/NO-GO cue), and reward period. Activities of GO cue-coupled neurons,
      intermediate neurons and movement-coupled neurons in GO trials were recorded in
      layers II-VI, layers II-VI and layers III-VI of the area 8, respectively.
      Activities of NO-GO cu-coupled and NO-GO response-related neurons in NO-GO trials
      were recorded in layers II-VI and layers III-VI, respectively. It was considered
      that task-related visual information may be fed to layer III and IV, as a GO/NO
      GO cue coupled activity, and then flow upward and/or downward to layers III-VI
      where movement-coupled activities are recorded. NO-GO response-related activity
      appears to suppress GO activity in layers III-VI. It was noted that the laminar
      distribution of NO-GO response-related neurons was similar to that of movement
      coupled neurons in GO trials, and that the shape of spikes of NO-GO response
      related neurons in our study resembled that of spikes of putative GABAergic
      neurons in a previous study. These results suggest that NO-GO response-related
      neurons are involved in response inhibition through GABAergic mechanisms.

PMID- 9622798
TI  - Transcranial AC pulsed applications of weak electromagnetic fields reduces
      freezing and falling in progressive supranuclear palsy: a case report.
AB  - Freezing is a common and disabling symptom in patients with Parkinsonism. It
      affects most commonly the gait in the form of start hesitation and sudden
      immobility often resulting in falling. A higher incidence of freezing occurs in
      patients with progressive supranuclear palsy (PSP) which is characterized
      clinically by a constellation of symptoms including supranuclear ophthalmoplegia,
      postural instability, axial rigidity, dysarthria, Parkinsonism, and pseudobulbar
      palsy. Pharmacologic therapy of PSP is currently disappointing and the disease
      progresses relentlessly to a fatal outcome within the first decade after onset.
      This report concerns a 67 year old woman with a diagnosis of PSP in whom freezing
      and frequent falling were the most disabling symptoms of the disease at the time
      of presentation. Both symptoms, which were rated 4 on the Unified Parkinson
      Rating Scale (UPRS) which grades Parkinsonian symptoms and signs from 0 to 4,
      with 0 being normal and 4 being severe symptoms, were resistant to treatment with
      dopaminergic drugs such as levodopa, amantadine, selegiline and pergolide
      mesylate as well as with the potent and highly selective noradrenergic reuptake
      inhibitor nortriptyline. Weekly transcranial applications of AC pulsed
      electromagnetic fields (EMFs) of picotesla flux density was associated with
      approximately 50% reduction in the frequency of freezing and about 80-90%
      reduction in frequency of falling after a 6 months follow-up period. At this
      point freezing was rated 2 while falling received a score of 1 on the UPRS. In
      addition, this treatment was associated with an improvement in Parkinsonian and
      pseudobulbar symptoms with the difference between the pre-and post EMF treatment
      across 13 measures being highly significant (p < .005; Sign test). These results
      suggest that transcranial administration AC pulsed EMFs in the picotesla flux
      density is efficacious in the treatment of PSP.

PMID- 9622797
TI  - Contralateral transient evoked otoacoustic emissions following acoustic neuroma
      surgery.
AB  - This study aimed to evaluate the effect of acoustic neuroma surgery on the
      contralateral cochlear function using transient evoked otoacoustic emissions
      (TEOAEs) and to test whether changes in TEOAEs differ according to the type of
      surgical approach. Forty four patients were included in this study. TEOAEs were
      recorded in both ears one day before (D0) and one month after surgery (D30). At
      D30, 20.5% of the patients showed an increase, 22.7% showed a decrease in
      contralateral TEOAEs amplitude and 56.8% remained stable. In the ear ipsilateral
      to the neuroma, TEOAE amplitude was significantly lower at D0 in the "increased"
      group compared to the "decreased" one. In the contralateral ear, TEOAE amplitude
      was significantly lower at D0 and D30 in the "increased" group compared to the
      "decreased" one and at D0 compared to the "stable" one. According to the surgical
      approach the patients were divided into two groups: a Translabyrinthine (TL)
      group (56.8% patients), and a retrosigmoid (RS) group (43.2% patients). The
      percentage of patients who presented an "increase" in TEOAEs amplitude in the
      contralateral ear was higher in the RS group (31.5) compared to the TL one (12%).
      The PTA lost at D0 was significantly higher in the TL group compared to the RS
      group. The TEOAE amplitude was significantly higher at D0 in both ipsi- and
      contralateral ears in the TL group compared to the RS one. These results suggest
      that acoustic neuroma removal is responsible for changes in contralateral TEOAEs.
      It can be hypothesized that changes in the efferent fibers secondary to surgery
      could partly explain these results.

PMID- 9622799
TI  - The curvelinear correlations between the total testosterone levels and fluid
      intelligence in men and women.
AB  - The relationship between serum total testosterone (T) level and the fluid
      intelligence (Cattell's Culture Fair Intelligence Test) was studied in men and
      women. There was no significant difference between IQs of men and women. There
      was an inverse curvelinear relationship between IQ and T in women. The same was
      found also in men, but the declining part of the regression line at high T levels
      was not as pronounced as in women. It is concluded that T may be related to IQ,
      even in subjects exhibiting no sex difference in IQ tests; too low or too high T
      levels may be disadvantages for the fluid intelligence, especially in women.

PMID- 9622800
TI  - Ventricular dilation over several weeks following induction of excitotoxic
      (systemic lithium/pilocarpine) lesions: potential role of damage to the
      substantia nigra reticulata.
AB  - Time-dependent atrophy of cerebral space and enlargement of the lateral
      ventricles were noted in healthy rats 1 to 100 days after the induction of
      seizures by a single systemic injection of lithium and pilocarpine. The rate of
      atrophy was most strongly correlated (0.90) with the log (base 10) of the time in
      days. Most of the degeneration had occurred within about 20 to 30 days after the
      seizure-induced brain trauma. Concomitant reduction in the area of the substantia
      nigra reticulata was the most powerful predictor of ventricular enlargement at
      the level of the caudate-putamen.

PMID- 9622801
TI  - Executive functioning as outcome in patients after traumatic brain injury.
AB  - The present study was designed to determine how traumatic brain injury affect
      executive functioning, to know whether different treatments in the acute phase
      improve this functioning, and to check whether the severity of the neurocognitive
      impairment is detected by the Glasgow Outcome Scale (GOS). Ability for problem
      solving and executive functioning within 2 years after Traumatic Brain Injury
      (TBI) was examined in 35 conscious survivors. Two groups were formed. One group
      consisted of 13 patients who needed neurosurgery. The other group was made up of
      22 patients without neurosurgical treatment. All were treated in the
      Neurosurgical Intensive Care Unit and in the Rehabilitation Service. The
      following variables were registered: Secondary Lesions, Glasgow Coma Scale (GCS),
      CT, subacute CT, and Glasgow Outcome Scale. Neuropsychological tests administered
      were Wisconsin Card Sorting Test (WCST) and the Tower of Hanoi/Sevilla. Comparing
      both groups' test performance (man Whitney U) we found that a severe traumatic
      brain injury, whatever the treatment applied in the acute phase, impairs the
      executive functioning of the patients; this impairment is related to acute
      pathophysiological events. The neurosurgical intervention does not improve the
      executive functioning. The Glasgow Outcome Scale does not detect more than 25% of
      the patients with severe impairment. It is suggested that the Tower of
      Hanoi/Sevilla could be a good tool to evaluate the executive functioning
      routinely in TBI patients as outcome. It also suggested that mild TBI patients
      must be referred for a complete neuropsychological examination.

PMID- 9622802
TI  - Evaluation of two brief and reliable estimates of the WAIS-R.
AB  - Performance of 200 mixed neuropsychiatric patients on the WAIS-R were compared to
      the summary scores for Kaufman's Brief Intelligence Test (K-BIT) and a seven
      subtest short form of the WAIS-R. Correlations between verbal, non-verbal, and
      composite of the full WAIS-R with the K-BIT were significantly lower than the
      correlations with the WAIS-R shore form. The percentage of cases on the short
      forms that fell within 5 points of the full WAIS-R was higher for the seven
      subtest version of the WAIS-R than the K-BIT. Specifically, Verbal,
      Nonverbal/Performance, and Composite/Full Scale scores on the WAIS-R short form
      feel within 5 points for 89%, 74%, and 92% of the cases while on the K-BIT only
      52%, 40%, and 50% fell within 5 points.

PMID- 9622803
TI  - [Report edited by J Perret, president of the jury, after presentations of
      experts. Consensus conference on the indications for emergency EEG. Tours, May,
      1996)].

PMID- 9622804
TI  - [Emergency EEG and brain injuries].
AB  - The aim of this study is to review indications for emergency EEG in case of brain
      trauma. The authors emphasize the indication of emergency EEG for the diagnosis
      of either cerebral death or early post traumatic seizures, and for the monitoring
      of intensive neurological treatments. Emergency EEG and diagnosis of cerebral
      death has been reviewed in another issue of this journal. Diagnosis of early post
      traumatic seizures may be difficult in case of cranial trauma in either the
      presence or the absence of coma. Emergency EEG help guide the diagnosis of
      electrical signs of seizures, thus indicating that treatment with antiepileptic
      drugs is advisable. Severe post-traumatic coma requires barbiturate impregnation
      and moderate hypothermia. In this last case, emergency EEG is essential for the
      monitoring of pharmacological treatments. The authors conclude that continuous
      EEG monitoring could in the future substitute for standard EEG recorded in
      emergency.

PMID- 9622805
TI  - [Emergency indications of EEG in the situation of a head injury in children and
      adults].
AB  - After initial loss of consciousness following brain injury, background EEG may
      show slowing and posterior slow waves are observed, consistent with the existence
      of commotio cerebri, particularly in children. However, discrepancies between
      cerebral electrogenesis and the clinical condition may also persist for several
      weeks. As EEG is correlated with the stage of posttraumatic coma, its reactivity
      to stimuli is of value. While important EEG impairment with paroxysmal
      abnormalities is frequent in children, the patients' outcome is poorly correlated
      with initial EEG record. In intensive care units, the use of continuous digitized
      EEG techniques has opened new avenues. Though in case of mild risks, EEG and
      clinical follow-up may be sufficient after brain injury, EEG recording is
      recommended when computerized tomography (CT-scan) is normal in case of severe
      risks. When consciousness impairment is unexplained by the importance of the
      brain injury, emergency CT-scan is recommended, searching for intracranial
      hematoma. If CT-scan proves to be normal EEG should then be recorded, searching
      for local injury. EEG may uncover non-convulsive status epilepticus, mainly in
      elderly patients. In case of early seizures, EEG recording should be done within
      the first 24 hours following brain injury. In the post-ictal period, EEG should
      be recorded in emergency in case of confusional state lasting more than 30
      minutes, as potential non-convulsive status epilepticus should not be
      underestimated. EEG is not of good predictive value for posttraumatic epilepsy;
      however, the existence of paroxysmal, local abnormalities is a risk factor.
      Recording of abnormalities may be useful for the medico-legal expert.

PMID- 9622806
TI  - [Indications for EEG in mental confusion and behavior problems].
AB  - Even in 1998 at the time of brain imaging, EEG recording is undoubtedly useful in
      clinical psychiatry when a true cerebral disease takes the form of an acute
      psychiatric disorder. Though the real place of EEG recording cannot be yet
      accurately quantified, it may help guide the diagnosis, as it is of either
      positive (ie, confirming the diagnosis via additional information) or negative
      (ie, rejecting various etiologies) value. Most of the time, only the former is
      considered in published studies. The clinical value of EEG recording in
      psychiatry emergency unit is therefore still not clearly established. The study
      of patients admitted during two years in the emergency unit at Sainte-Anne
      hospital (Paris, France) does not bring new conclusions, mainly because of bias
      in the modalities of admission and follow-up. As well, the role of EEG recording
      for the diagnosis of non-psychiatric diseases in psychiatry emergency units
      cannot be defined today. The authors review clinical situations where EEG
      recording is still highly advisable.

PMID- 9622807
TI  - [Emergency electroencephalography during perinatal cerebral intensive care:
      indications and results].
AB  - The main contribution of EEG during intensive care in infants with hypoxic
      ischemic encephalopathy is i) to help determine whether infants with subtle
      clinical manifestations present with epileptic seizures, ii) to determine whether
      paralyzed or heavily sedated infants present with convulsive phenomena, iii) to
      assess the therapeutical response to anticonvulsants, 4) to contribute, in
      combination with ultrasound scanning, to diagnostic evaluation of the severity of
      lesions, and to provide valuable prognostic informations via the analysis of the
      background activity, as normal EEG is highly predictive of normal outcome,
      whereas various abnormal EEG features are constantly associated with subsequent
      major neurological abnormalities or death. These EEG features are readily
      available from a very early stage and may both precede and be prognostically more
      sensitive than information obtained from ultrasound. Recording of neonatal
      electroencephalogram requires awareness of the normal development of
      electroencephalographic features in the newborn, skilled technicians, and
      experienced readers of EEG tracings.

PMID- 9622808
TI  - A pediatrician's view. A brief history of group A beta hemolytic strep.

PMID- 9622809
TI  - Diagnosis of group A streptococcal pharyngitis.

PMID- 9622811
TI  - Streptococcal pharyngitis: the carrier state, definition, and management.

PMID- 9622810
TI  - Current therapy of group A streptococcal pharyngitis.

PMID- 9622812
TI  - Severe, invasive group A streptococcal disease and toxic shock.

PMID- 9622813
TI  - Acute rheumatic fever: diagnosis and treatment.

PMID- 9622814
TI  - Group A streptococcal vaccines.

PMID- 9622815
TI  - [Standards and diagnostic strategies].

PMID- 9622816
TI  - [The quality offensive in radiology].
AB  - The Institute of Diagnostic Radiology at the Heinrich-Heine-University
      Duesseldorf has recently defined and implemented more than thirty organizational
      changes as a result of a quality control project. The aim was to improve quality
      and efficiency of the Radiology service. The project was carried out in
      cooperation with an external consulting firm. To date the positive impact of this
      project on our work has been so profound that we would like to communicate some
      of the results in form of this report. During the first phase of the project
      quality circles were formed to define the various quality criteria and aims of a
      good service. Today these represent the core of a new quality policy for the
      Institute. In a second phase all members of staff cooperatively developed precise
      plans of action for implementation of the necessary changes. Main achievements
      are the reduction of organizational and communicational deficits obstructing the
      work process, enhancement of interaction between junior and senior medical staff,
      upgrading of the role and field of action of the radiography staff and last but
      not least improvements of cooperation between secretarial and medical staff.

PMID- 9622817
TI  - [Study design in clinical radiologic research].
AB  - PURPOSE: To review important aspects of study design in clinical radiology and to
      introduce the reader to the requirements of Good Clinical Practice (GCP).
      METHODS: The European guidelines for GCP, the Declaration of Helsinki, the
      differentiation into study phases and the authors' own experience in open and
      sponsored clinical trials are the basis of this analysis. RESULTS: Guideline such
      as GCP do not limit scientific freedom in research but define high standards for
      the well-being of patients and volunteers as well as guaranteeing scientific
      honesty. The benefits of defined data monitoring and the necessity of a
      prospective statistical concept are frequently underestimated. CONCLUSION:
      Correct study design has to be expected in radiology too. High standards
      guarantee accuracy and honesty of scientific studies. Only this can warrant the
      value for the patient of radiological diagnostics and therapy.

PMID- 9622818
TI  - [Spiral CT angiography in diagnosis of acute pulmonary embolism. What factors
      modify implementation of standard algorithms?].
AB  - PURPOSE: Debate about the potential implementation of Spiral-CT in diagnostic
      algorithms of pulmonary embolism are often focussed on sensitivity and
      specificity in the context of comparative methodologic studies. We intend to
      investigate whether additional factors might influence this debate. MATERIALS AND
      METHODS: On the basis of the current literature and of own experience we study
      the influence of factors such as availability, acceptance, patient-outcome, and
      cost effectiveness-studies on the potential implementation of Spiral-CT in
      diagnostic algorithms of pulmonary embolism. This information is analyzed
      together with data from comparative methodologic studies. RESULTS: The factors
      availability, acceptance, patient-outcome, and cost-effectiveness-studies do have
      substantial influence on the implementation of Spiral-CT in the diagnostic
      algorithms of pulmonary embolism. Incorporation of these factors into the
      discussion might lead to more flexible and more patient-oriented algorithms for
      the diagnosis of pulmonary embolism. CONCLUSION: Availability of equipment,
      acceptance among clinicians, patient-outcome, and cost-effectiveness evaluations
      should be implemented into the debate about potential implementation of Spiral-CT
      in routine diagnostic imaging algorithms of pulmonary embolism.

PMID- 9622819
TI  - [Diagnosis of bronchial carcinoma].
AB  - In addition to conventional chest X-rays in AP and lateral projection, computed
      tomography of the chest, upper abdomen, and head, precutaneous ultrasonography of
      the abdomen, and bone scintigraphy represent the standard procedures for the
      primary diagnosis and staging of bronchial carcinoma. Magnetic resonance imaging
      should be reserved for special situations and patients with allergy to i.v.
      contrast medium. The clinical value of positron emission tomography (PET)
      primarily with respect to lymph-node staging is currently being evaluated in
      ongoing studies. Due to the high sensitivity of the listed staging modalities in
      combination with rather low specificity, there is a general tendency towards
      "over staging", which carries certain risk particularly for potentially operable
      patients. Consequently the criteria which indicate inoperability (T3, T4, N2, N3
      and, in individual cases, M1) have to be confirmed histologically by biopsy
      employing interventional techniques or even by explorative thoracotomy before
      definite therapeutic decisions are made.

PMID- 9622820
TI  - [Focal liver diseases].
AB  - INTRODUCTION: Advanced therapies are improving significantly the survival of
      patients with malignant focal liver disease. For efficient implementation of
      these surgical and interventional techniques a clear concept of the diagnostic
      procedure is mandatory. METHODS: Based on a review of the current literature, the
      different imaging modalities, including ultrasound, computed tomography, magnetic
      resonance tomography, nuclear medicine and angiography, are discussed and
      evaluated for their diagnostic efficacy in focal hepatic disease. RESULTS:
      Considering clinical, diagnostic, and economical appropriateness, recommendations
      for diagnostic strategies in different clinical scenarios regarding focal heptic
      disease are presented. CONCLUSION: If the power of specific imaging methods are
      relevant clinical information is known, problem-based diagnostic strategies help
      to avoid unnecessary, expensive and time-consuming studies in the work-up of
      focal liver lesions.

PMID- 9622821
TI  - [Rational diagnosis of the bile ducts].
AB  - Since the introduction of MR cholangiography (MRC) diagnostic imaging of the
      biliary tract has been significantly improved. While percutaneous ultrasonography
      is still the primary examination, computed tomography (CT), conventional magnetic
      resonance imaging (MRI), as well as the direct imaging modalities of the biliary
      tract--i.v. cholangiography, endoscopic-retrograde-cholangiography (ERC), and
      percutaneous-transhepatic-cholangiography (PTC) are in use. This article
      discusses the clinical value of the different diagnostic techniques for the
      various biliary pathologies with special attention to recent developments in MRC
      techniques. An algorithm is presented offering a rational approach to biliary
      disorders. With further technical improvement shifts from ERC(P) to MRC(P) for
      biliary imaging could be envisioned, ERCP further concentrating on its role as a
      minimal invasive treatment option.

PMID- 9622822
TI  - [Hydro-CT in detection and staging of pancreatic carcinoma].
AB  - PURPOSE: To document our experience with spiral hydro-CT of the pancreas based on
      a combination of pharmacologic intestinal paralysis and water distension of the
      stomach and duodenum with specific reference to tumor detection rate,
      differentiation of malignant versus benign tumors and assessment of tumor
      resectability in a prospective study on 211 consecutive patients. MATERIAL AND
      METHODS: Between May 1994 und September 1997, 211 patients with suspect of
      pancreatic neoplasm from clinical, laboratory or other imaging data were
      examined. Our Hydro-CT techniques were based on intravenous injection of 40 mg N
      butylscopolaminiumbromid (Buscopan) for intestinal paralysis, gastric and
      duodenal wall distension by oral administration of an average of 1.5 l warm tap
      water, 30 degrees RAO patient's positioning, individualized contrast injection
      technique using portal vein enhancement as reference and thin slice spiral CT (3
      mm slice thickness, 6 mm table feed and 3 mm secondary reconstruction). Examined
      parameters were: (1) tumor detection rate, (2) differentiation of malignant
      versus benign disease, (3) differential diagnosis and (4) accuracy of assessment
      of resectability by identification of infiltration into adjacent organs and
      vessel structures relevant for resectability such as splenic, superior
      mesenteric, portal vein and celiac trunk, superior mesenteric, splenic and
      hepatic arteries. As gold standard for positive tumor detection and description
      surgery (of potentially resectable tumors) and microscopic diagnosis (of clearly
      unresectable tumors) were used and for negative tumor detection an event-free
      survival of six months, respectively. RESULTS: 96% of the examinations were well
      tolerated. In only 4% was on-site administration of a gastric tube required
      because of vomiting. In 2% of the patients a slight allergic reaction to the
      contrast medium was seen. The prevalence of a pancreatic neoplasm was 37.8%. In
      tumor detection Hydro-CT reached an overall accuracy of 94.8% with a sensitivity
      of 93.7% and a specificity of 95.2%. 52 patients underwent surgical exploration
      34 of whom with tumorfree resection margins (RO resection) corresponding to a
      resection of 42.5%. In those assessment of resectability reached an overall
      accuracy of 94.6% with a sensitivity of 91.2% and specificity of 95.6%.
      CONCLUSION: The new technique of Hydro-CT based on the slice and spiral
      methodology including pharmacologic intestinal paralysis and water distension
      results in a high tumor detection rate and reliable assessment of resectability.

PMID- 9622823
TI  - [Standards and diagnostic strategies in diagnosis of bone tumors and tumor
      simulating lesions].
AB  - Real bone tumors are rarely encountered in the daily routine of radiological
      practice. Therefore, for a general radiologist there is no need for a specialist
      knowledge on this field. However, he should be able to distinguish benign from
      malignant lesions in order to avoid unnecessary biopsies. A systematic approach
      towards osteolytic lesions, e.g. according to the classification of Lodwick, is
      mandatory. CT and MRI are indicated to clear up the anatomy in areas of
      superposition artefacts in conventional radiology and to determine the inner
      structure of a lesion, e.g. fatty tissue, liquid/solid. This paper highlights the
      advantages and disadvantages and the cost-effective use of the imaging modalities
      including scintigraphy in the diagnosis of bone tumors and tumor-like lesions.
      Guidelines for the management of bony lesions will be given in detail. The option
      and necessity for a specialist second opinion is emphasized.

PMID- 9622824
TI  - [Acute roentgen diagnosis of battered child syndrome. A strategy].
AB  - A strategy is proposed for the dedicated interpretation of possible radiographic
      plain film signs that are suspicious for indicating child abuse. For each sign,
      the features "PRO" raise the question of abuse, while radiographic or clinical
      findings "CON" suggest an alternate explanation. Birth trauma, oesteogenesis
      imperfecta, rescue trauma, and metastatic neuroblastoma are among the many
      entities cited. A triad of situations may lead a radiologist to look
      systematically for changes from abuse; a triad of resolutions may result from the
      search. Periosteal reactions is the major factor in dating of fractures;
      physiologic periosteal reaction of infancy and periosteal reaction from previous
      fracture must be considered when so dating fractures.

PMID- 9622825
TI  - [Multiple reader analysis for evaluation of functional MR mammography].
AB  - The diagnostic impact and reproducibility of the different methods used within
      the concept of functional MR-Mammography (FMRM) was assessed by a multi-reader
      analysis. By four experienced readers, 100 histologically confirmed cases were
      evaluated in six different sessions. Per session, one of the following components
      was analyzed: clinical history (I), static MRM (II), color-coded projection
      images (III), time-signal curves of contrast enhancement within a large ROI (IV)
      and the strongest enhancing pixel (V) obtained from the histologically confirmed
      lesion and the complete FMRM reading (VI). The functional methods (IV-VI)
      revealed significantly (p < 0.05) higher specificities than the others (I-III).
      The highest reproducibility between the readers was observed for (IV) phi chi =
      0.80, (V) phi chi = 0.76 and FMRM (VI) phi chi = 0.63. These three methods also
      presented the best ROC-curves and showed the highest complementarity with respect
      to the false positive classifications in x-ray mammography. FMRM is a reader
      independent, reproducible method. The analysis of the contrast enhancement time
      intensity curves with high temporal resolution allows an improved differentiation
      of malignant and benign findings.

PMID- 9622827
TI  - [Time and image].

PMID- 9622826
TI  - [Quantitative morphology of vertebral body cortical bone. Building block for
      noninvasive calculation of fracture threshold in osteoporosis].
AB  - The vertebral bodies consist of two main structures, trabecular and cortical
      bone. The histological changes within the spine, especially in cortical bone,
      leading to osteoporotic fractures remain, however, poorly understood. Therefore,
      the complete front column of the spine was removed in 26 autopsy cases without
      skeletal diseases and in 11 cases with proven osteoporosis. A sagittal segment
      prepared through the center of all vertebral bodies was undecalcified embedded in
      plastic, ground to a 1-mm-thick block and stained using a modification of the von
      Kossa method. The analysis included measurement of the mean cortical thickness of
      both ventral and dorsal shell (from C3 to L5). The qualitative investigation of
      the structure of the cortical ring completed the analysis. The skeletally intact
      specimens had high cortical thickness values in the cervical spine (285 +/- 22
      microns), a decrease in the thoracic spine (244 +/- 14 microns) and an increase
      in the lumbar spine (290 +/- 15 microns). The mean thickness of the ventral shell
      is in general higher than the thickness of the dorsal shell. The cortical
      thickness of the spine showed no gender-specific differences (P = n.s.). There
      was a slight decrease in the cortical thickness with age; however, this decrease
      and the correlation of cortical thickness to age was only significant below
      vertebral body T8 (r = 0.225 to 0.574; Pr < 0.05 to Pr < 0.005). Most
      interestingly, osteoporosis is characterized by a significant decrease in
      cortical thickness throughout the whole spine. This decrease in cortical
      thickness was more marked in the dorsal shell (P < 0.05) than in the ventral
      shell (ventral from C3 to T6 (P < 0.05) below T6 (P = n.s.). We therefore
      conclude that in osteoporosis, biomechanical competence is affected by both
      trabecular bone loss and decrease of cortical thickness. This suggests that, in
      addition to trabecular bone measurements, the cortical thickness is of special
      interest for diagnostic radiological examinations (CT) to yield clues about the
      risk of vertebral fractures.

PMID- 9622828
TI  - [Space-occupying lesion in the pelvis. Hemorrhagic, cystic ovarian tumor].

PMID- 9622829
TI  - [MRI for the orthopedist. Position of the ARGE Professional Organizations Medical
      Radiology and the German Roentgen Society].

PMID- 9622830
TI  - [Radiology scenario 2000. Need-based management, economics and graduate education
      in diagnostic radiology: the quadrature of the circle? 1].

PMID- 9622831
TI  - [Radiologists support KBV by the "IGEL" concept].

PMID- 9622832
TI  - [The dry period will still last a while].

PMID- 9622833
TI  - [Equal distribution or appropriateness of coverage. What is left when one or the
      other is lost in physician self-regulation?].

PMID- 9622837
TI  - [Age-related seroprevalence of measles, mumps and rubella antibodies in 1996].
AB  - In 1996 the effects on the immunity profile of a Swiss population exposed to MMR
      vaccination, which has been recommended since 1985, were evaluated with an age
      stratified seroprevalence study for measles, mumps and rubella (MMR). At the age
      of 1.5-2.5 years, seroprevalence attained 76% for measles and rubella, which is
      respectively 17% and 24% above the values observed in 1992. The seroprevalence
      for mumps attained only 55% at the same age, which could reflect the poor
      immunogenicity of this component of the MMR vaccine. The seroprevalence for
      measles IgG showed a slow but steady increase from vaccination age to adulthood,
      attaining nearly 100%. The concentrations of measles IgG were about 700 IU/l into
      adolescence and rose to a plateau at about 1500 IU/l during young adulthood.
      These observations are compatible with low endemic activity of measles in the
      last 20 years and a predominance of vaccine-induced immunity up to about 20 years
      of age. This corresponds to the time period when measles vaccines--single or as
      MMR--have been in use. In 1992, at the peak of epidemic activity, seroprevalence
      for mumps rose substantially faster than in 1996. In addition, the rapid increase
      in quantitative values during preschool age mirrors the ongoing wild virus
      circulation with minimal vaccine effect. In the vaccine cohort (2-12 years of
      age) the seroprevalence of rubella IgG reached 70-80%. That there is no rise in
      the curve during school age shows that the recommended catch-up vaccinations
      before or during school age have been neglected. The median concentrations of
      rubella IgG were about 65 IU/ml at vaccination, declined to 40-50 IU/ml during
      preschool age, and rose again during school age, suggesting wild virus
      circulation. These data show that the MMR vaccine cover in Swiss children is
      insufficient to interrupt virus circulation, and administration of a second dose
      of MMR for catch-up immunisation has been omitted. The poor efficacy of the mumps
      component of the MMR vaccine that has mainly been used in Switzerland is also
      evident. The average age at infection is therefore expected to rise, thus
      involving a risk of increasing age-dependent complications. Efforts to implement
      the MMR vaccination program in Switzerland should be improved.

PMID- 9622838
TI  - [Intensive monitoring of patients with acute cerebral ischemia within the scope
      of a coordinated stroke treatment concept: initial experiences].
AB  - QUESTIONS UNDER STUDY: It has been shown that the prognosis of patients with
      stroke can be improved by specialized stroke units. Whether any additional
      benefit can be achieved by use of intensive care resources is unknown. Therefore,
      it was the purpose of this study to analyze our first experience of management of
      patients with acute ischaemic stroke in an intensive care unit, as part of a
      newly implemented coordinated stroke concept. METHODS: A consecutive series of 88
      patients with acute ischemic stroke (age 64.4 +/- 14.2 years, 28% females)
      hospitalized in a medical intensive care unit according to predefined criteria
      formed the study population. The goals were to monitor vital functions, to
      complete diagnostic studies in timely fashion and to prevent and treat
      complications. RESULTS: The patients were hospitalized in the intensive care unit
      for a mean period of 34.4 +/- 19.5 hours. Relevant pathologic findings included
      systolic hypertension > 220 mm Hg in 5% and permanent or intermittent relative
      systolic hypotension < 150 mm Hg in 25% and 98% of patients respectively. One
      patient (1%) died during the stay. Additional diagnostic studies were performed
      more often in patients with progressive or fluctuating symptoms (100% of patients
      in each group) than in those with improving or stable symptoms (50% of patients
      in each group). Fourteen percent of patients were treated for hypertension and
      30% for hypotension. Antithrombotic therapy with aspirin was started in 34%,
      prophylaxis for venous thrombosis with low dose heparin in 39% and systemic
      anticoagulation in 40% of patients respectively. No cardiac or pulmonary
      complications requiring treatment were observed and no specific therapies for
      neurologic complications were utilized. At the time of discharge from the
      intensive care unit, 88% of patients showed improved or stable neurologic
      findings. CONCLUSIONS: In the present analysis, an unexpectedly high incidence of
      relative arterial hypotension was observed in patients hospitalized in an
      intensive care unit for acute ischaemic stroke. Therapeutic measures were
      restricted mainly to blood pressure control and anticoagulation/antithrombotic
      treatment. Specific therapies for neurologic complications or interventions
      requiring the resources of an intensive care unit were not used. Whether defined
      patient groups with ischaemic stroke will benefit from specific treatment in an
      intensive care unit needs to be tested by controlled, randomized studies.

PMID- 9622839
TI  - [Lipid lowering therapy: new pathophysiologic aspects and clinical implications].
AB  - Lipid-lowering therapy reduces cardiovascular morbidity and mortality. Although
      atherosclerotic plaques regress under lipid-lowering therapy, only minor changes
      in arteriosclerotic plaques are angiographically detectable. These changes cannot
      fully explain all the benefits of lipid-lowering therapy. Additional factors
      independent of macroscopically detectable alterations in plaque size may
      contribute to the clinical effects of lipid-lowering therapy. Qualitative changes
      in the composition of atherosclerotic plaques may reduce the risk of subsequent
      plaque rupture. Furthermore, hypercholesterolemia is associated with endothelial
      dysfunction, i.e., impaired endothelium-mediated vasodilation, induction of
      adhesion molecules, and altered expression of growth factors. Lipid lowering
      seems to reverse endothelial dysfunction. Also, lipid-lowering therapy may reduce
      peripheral arterial resistance and hyperinsulinemia, and may improve erythrocyte
      deformability. These effects of lipid-lowering therapy may contribute to the
      clinical benefits. In particular, the concept of endothelial dysfunction as a
      first, reversible manifestation of target organ damage deserves further attention
      in the diagnosis and therapy of cardiovascular disease.

PMID- 9622840
TI  - [High altitude stay and air travel in coronary heart disease].
AB  - Acute exposure to high altitude produces hypoxia-associated stimulation of the
      sympathetic nervous system. This response is further enhanced by physical
      activity and induces an increase in heart rate and blood pressure. Consequently,
      cardiac work, myocardial oxygen consumption, and coronary blood flow are also
      increased. During the first 4 days of acute exposure to moderate or high
      altitude, coronary patients are at greatest risk of untoward events. Gradual
      ascent, early limitation of activity to a lower level than tolerated at low
      altitude, pre-ascent physical conditioning and rigorous blood pressure control
      should all help to minimise the cardiac risk. At altitudes of 2500 to 3000 m or
      lower, an asymptomatic coronary patient with good exercise tolerance, without
      exercise induced signs or symptoms of ischemia, and with an ejection fraction of
      the left ventricle > 50%, is at very low risk. However, several days'
      acclimatization before high-level activity at moderate or high altitude is
      recommended. High risk coronary patients should be investigated more carefully
      and precautionary measures should be more stringent. Left and right cardiac
      function and pulmonary artery pressure are the most helpful parameters for
      evaluation and counselling of patients with non-ischemic heart disease who plan
      to ascend to moderate or high altitudes. When advising patients who intend to fly
      as passengers in commercial aircraft, it is important to know that in-flight
      atmospheric pressure conditions in commercial jet aircraft approach altitude
      equivalents of 1500 to 2400 m. Propeller-driven planes are rarely pressurized but
      usually fly at altitudes below 3300 m. Relatively strict contraindications for
      air travel by coronary patients are uncomplicated myocardial infarction within
      the last 2 weeks, complicated myocardial infarction within the last 6 weeks,
      unstable angina, thoracic surgery within the last 3 weeks, and poorly controlled
      congestive heart failure, arrhythmia, or hypertension.

PMID- 9622841
TI  - [Intermittent visual hallucinations].

PMID- 9622842
TI  - [Blood groups and structure-activity relations].
AB  - In the recent years, advances in biochemistry and molecular genetics have
      contributed to establish the structure of the genes and proteins from most of the
      23 blood group systems presently known. From these findings, five functional
      classes of molecules can be schematically distinguished: (i) transporters and
      channels, (ii) receptors for ligands, viruses, bacteria and parasites, (iii)
      adhesion molecules, (iv) enzymes, and (v) structural proteins. Recent advances on
      these molecules will be reviewed, particularly by illustrating available
      structure-function relationships.

PMID- 9622843
TI  - [Unconventional transmissible agents: risk of transmission by blood].

PMID- 9622844
TI  - [Quality assurance in blood transfusion: the advantages and limitations].

PMID- 9622845
TI  - [From immunohematology to molecular biology].

PMID- 9622846
TI  - Catalytic activities, protein- and mRNA-expression of cytochrome P450 isoenzymes
      in intestinal cell lines.
AB  - 1. Certain chemicals and drugs in addition to metabolically activated carcinogens
      are substrates for intestinal cytochrome P450s (CYPs) and a number of cell lines
      are available which could be used in metabolism studies. These include the rat
      duodenal cell line IEC 6, rat ileal IEC 18, foetal human HuTu 80, foetal human
      small intestinal FHS 74, human duodenal HCT 8 and human colon CaCo-2 cells, but
      they lack thorough biochemical characterization. 2. The aim of the present study
      was therefore to investigate the mRNA and protein expression of CYP1A1, CYP1A2,
      CYP2C9/10, CYP2E1 and CYP3A. In addition, the metabolism of the immunosuppressant
      drug tacrolimus and of the procarcinogen 7,12-dimethyl-benz[a]anthracene (DMBA)
      was studied to obtain information on the functional activity on these cell lines.
      3. Of all the cell lines tested only CaCo-2 cells expressed CYP1A1 at the protein
      and mRNA level, but the CYP2E1 and CYP3A protein was also detected in CaCo-2 and
      FHS 74 cells. It is of considerable interest that none of the other cell lines
      expressed CYP1A1, CYP1A2, CYP2C9/10 or CYP3A4 at the protein and mRNA level. 4.
      When the metabolism of DMBA (a model carcinogen) was studied, CaCo-2 cells
      produced the following metabolites: 7,12-dihydroxymethylbenz[a]anthracene, 7,12
      dimethylbenz-[a]anthracene-di-hydrodiol, 7-methyl-12
      hydroxymethylbenz[a]anthracene, 7-hydroxy-methyl-12-benz[a]anthracene and
      possibly the dihydrated product of the latter two derivatives. 5. CaCo-2 cells
      also catalysed the metabolism of the immunosuppressant drug tacrolimus resulting
      in the formation of 13-O-demethyl-tacrolimus bisdemethyl-hydroxy-tacrolimus and
      demethyl-dihydroxy-tacrolimus. Neither the foetal human small intestinal FHS 74
      cell line nor any of the other cell lines were able to catalyse the
      biotransformation of tacrolimus. 6. In conclusion, only CaCo-2 cells were able to
      produce metabolites similar to those observed in in vivo metabolism studies,
      whereas all other cell lines were metabolically incompetent. Therefore, this cell
      line may be used in studies of intestinal biotransformation.

PMID- 9622847
TI  - Glutathione S-transferases in human renal cortex and neoplastic tissue: enzymatic
      activity, isoenzyme profile and immunohistochemical localization.
AB  - 1. Glutathione S-transferase (GST) activity in the cytosol of renal cortex and
      tumours from eight men and eight women was measured using 1-chloro-2,4
      dinitrobenzene (CDNB) as a substrate. GST activities ranged from 685 to 2192
      nmol/min/mg protein in cortex (median 1213) and from non-detectable (minimum 45)
      to 2424 nmol/min/mg protein in tumours (median 469). The activities in the
      tumours were lower than those in the normal cortices (p < 0.05). 2. In men, the
      activity in the cortical cytosol was in all cases higher than that measured in
      the corresponding tumours (p < 0.05). In women, the difference in activity
      between cortices and tumours was not significantly different (p > 0.05). 3. The
      age of the patients ranged from 42 to 81 years (median 62) and was not found to
      play a role in the levels of GST activity observed in cortex or in renal tumours
      from either sex. 4. Immunoblotting and immunohistochemical studies confirmed that
      GST-alpha was the predominant form expressed both in normal cortex and tumour and
      probably accounted for most of the GST activity present in these samples. GST-mu
      and GST-phi were expressed in both tumours and normal cortex and, while in some
      cases the level of expression in the cortices was higher than that found in the
      tumours, the reverse was also observed. Within the GST-mu class, GST M1/M2 was
      only detected in one sample (tumour), which showed the highest overall expression
      of GST-mu. GSTM3 was the predominant isoenzyme of the mu class in normal and
      tumour tissue, whereas GTM4 and GSTM5 were not detected. 5. These differences
      could have functional significance where xenobiotics or cytotoxic drugs are
      specific substrates for the different classes of GSTs.

PMID- 9622848
TI  - Rat CYP24 catalyses 23S-hydroxylation of 26,26,26,27,27,27-hexafluorocalcitriol
      in vitro.
AB  - 1. Kidney mitochondrial 24-hydroxylase cytochrome P450 (CYP24) catalyses
      sequential hydroxylation at both C-24 and C-23 positions of calcidiol and
      calcitriol. Here, we have investigated the in vitro metabolism of a
      hexafluorinated derivative of calcitriol, 26,26,26,27,27,27-hexafluorocalcitriol
      (ST-630), in a reconstituted system by using recombinant Escherichia coli
      membrane fractions containing rat CYP24. 2. When ST-630 was incubated with CYP24
      supplemented with bovine adrenodoxin and NADPH-adrenodoxin reductase, a distinct
      metabolite could be observed. This metabolite was found to be 26,26,26,27,27,27
      hexafluoro-23S-hydroxcalcitriol, a biologically active metabolite of ST-630,
      based on cochromatography on HPLC and mass spectrometric analysis. 3. These
      results show the direct evidence that CYP24 plays an essential role in the
      metabolism of ST-630 to yield its 23S-hydroxylated metabolite, as observed in
      cultured cells and experimental animal studies.

PMID- 9622849
TI  - Enzyme-inducing effects of bicalutamide in mouse, rat and dog.
AB  - 1. Bicalutamide, a non-steroidal antiandrogen, produced dose-related increases in
      total cytochrome P450 (P450) and aldrin epoxidase, but had no effect on
      ethoxyresorufin O-deethylase, when administered for 10 weeks at 0, 25, 75 and 150
      mg/kg/day to the male dog. 2. In the male and female mouse, bicalutamide,
      administered orally at 75 mg/kg/day for 3 months, produced marked induction of
      total P450, ethoxycoumarin O-deethylase, pentoxyresorufin O-dealkylase and aldrin
      epoxidase. Immunoblotting showed that bicalutamide produced substantial induction
      of CYP2B isoforms, with lower increases in CYP3A. Immunohistochemistry of mouse
      liver sections also showed marked increases in the level of CYP2B isoforms, with
      an increase in the extent of distribution from centrilobular to panlobular; CYP3A
      isoforms were also increased, but to a lesser degree. 3. Bicalutamide,
      administered as 14 daily oral doses (250 mg/kg) to groups of male rats, produced
      increases primarily in ethoxycoumarin O-deethylase and erythromycin N
      demethylase, together with smaller increases in ethoxyresorufin O-deethylase and
      pentoxyresorufin O-dealkylase; these changes were reversible within 7 days.
      Immunoblotting of microsomes and immunocytochemistry of liver sections showed
      that bicalutamide markedly induced CYP3A1, but had little effect on CYP2B1 in
      rat. Compared with dexamethasone, bicalutamide is a more selective inducer of
      CYP3A1 in rat. 4. Bicalutamide, administered to rats as 14 daily oral doses of 10
      mg/kg, induced its own metabolism by stimulating both aromatic hydroxylation and
      direct glucuronidation. This effect was apparently offset by a concomitant
      decrease in hydrolysis of bicalutamide, resulting in no marked change in total
      amounts of dose eliminated over 2 days. 5. Although the secondary effects of
      enzyme induction result in thyroid hypertrophy and adenoma in rat and
      hepatocellular carcinoma in mouse following chronic administration of
      bicalutamide, these changes are considered to have little clinical relevance. In
      any case, bicalutamide does not produce enzyme induction in man at clinically
      relevant dose levels.

PMID- 9622850
TI  - Polychlorinated biphenyls affect the activities of gluconeogenic and lipogenic
      enzymes in rat liver: is there an interference with regulatory hormone actions?
AB  - 1. The effects of dietary polychlorinated biphenyls (PCBs) (30-2000 ppm) on
      activities of gluconeogenic (phosphoenolpyruvate carboxykinase-PEPCK, and
      fructose 1,6-bisphosphatase-FdPase) and lipogenic enzymes (fatty acid synthase
      FAS, ATP citrate lyase-ACL, malic enzyme-ME, glucose 6-phosphate dehydrogenase
      G6PDH, and 6-phosphogluconate dehydrogenase-PGDH) were studied in livers of the
      female Sprague-Dawley and Wistar rat. 2. PCB amounts accumulating in the liver
      reflected the extent of dietary exposure. The Wistar strain was more sensitive to
      PCBs than the Sprague-Dawley strain. Of the Clophentype PCBs those containing 60
      and 64% chlorine displayed the most pronounced effects. 3. Activities of
      gluconeogenic enzymes (PEPCK and FdPase) were dose-dependently decreased by PCBs,
      PEPCK being considerably more sensitive. This decrease was also found under
      conditions where the activity of PEPCK was induced (administration of adrenalin,
      glucagon or cAMP, feeding high protein diets, starvation). 4. Activities of
      lipogenic enzymes were induced by PCBs. The increase was much greater with ME,
      G6PDH and PGDH (up to 10-fold) than with FAS and ACL (approximately 2-fold). PCB
      effects were dose-dependent, but transient. 5. In cultured hepatocytes basal
      activities of lipogenic enzymes were induced by PCBs in the absence of hormones.
      With saturating levels of insulin or triiodothyronine, enzyme activities were
      also induced, but addition of PCBs resulted in an additive effect. 6. These
      results suggest that in the female rat PCBs can mimic the actions of certain
      hormones by affecting either hormone levels, hormone receptor systems or
      regulatory systems.

PMID- 9622851
TI  - Interlaboratory comparison of the assessment of P450 activities in human hepatic
      microsomal samples.
AB  - 1. Although the importance of in vitro technology in supporting drug development
      is widely accepted, there is no real consensus about which approaches should be
      taken, which substrates should be used, or on the reliability and application of
      in vitro data. Consequently, as part of a collaborative project to characterize
      human liver with respect to the major forms of cytochrome P450, an
      interlaboratory comparison of the analysis of samples for form-specific
      activities was undertaken. 2. Microsomal fractions were isolated from five
      different human liver samples taken from the liver bank maintained at the Royal
      Postgraduate Medical School (RPMS). Aliquots from the five samples were sent to
      the 11 collaborating laboratories for characterization using their in-house, form
      specific assays for cytochrome P450 activities. Although each laboratory assayed
      protein concentration, total cytochrome P450 content and enzyme activities were
      calculated using the protein estimation generated by RPMS to eliminate this
      possible source of variability. 3. With the exception of one laboratory, all
      estimates of protein concentration were similar (coefficient of variation, CoV, 9
      13%) and the rank-order of the five samples was consistent across the
      laboratories. There was greater variability in the estimates of total cytochrome
      P450 content (CoV 28-43%), although again rank order of the samples across
      laboratories was fairly consistent. 4. The various laboratories used a number of
      different probe substrates, together with a range of conditions (substrate
      concentration, time of incubation, amount of protein), to assay for activity of
      CYP1A2, CYP2C9, CYP2D6, CYP2E1 and CYP3A4. However, apart from the occasional
      outlier, the five samples were ranked for activity of all these forms of
      cytochrome P450 with a high degree of consistency by the various laboratories and
      the choice of substrate had no appreciable effect on the ranking of the samples.
      5. While this interlaboratory comparison has shown that greater consistency in
      the approach to in vivo determination of drug-metabolizing activity is desirable,
      there was little indication that any particular approach or substrate was
      superior to the others.

PMID- 9622852
TI  - Metabolism of 1-(3,4-dichlorobenzyl)-5-octylbiguanide in the dog.
AB  - 1. The biotransformation of 1-(3,4-dichlorobenzyl)-5-octylbiguanide (OPB-2045), a
      new potent biguanide antiseptic, was investigated in male beagle dogs. Urinary
      and faecal excretion of unchanged compound and metabolites were studied following
      a single subcutaneous injection of 14C-labeled compound at a dose of 1 mg/kg. 2.
      Four urinary metabolites were structually identified using synthetic standards
      and/or spectral data as 3,4-dichlorobenzoic acid, 6-[5-(3,4-dichlorobenzyl)-1
      biguanidino] hexanoic acid (DM-210), 4-[5-(3,4-dichlorobenzl)-1-biguanidino]
      butanoic acid (DM-212) and 5-[5-(3,4-dichlorobenzyl)-1-biguanidino] pentanoic
      acid (DM-213). 3. The predominant radioactive substances in the excreta were DM
      213 and DM-210 at 26.1% and 25.5%, respectively, of the dose. No unchanged
      compound was detected in the urine, and in the faeces it was only 2% of the dose.

PMID- 9622853
TI  - Pharmacokinetics of a novel benzodiazepine partial inverse agonist in the F344
      rat, SD rat and B6C3F1 mouse.
AB  - 1. The pharmacokinetics of a novel benzodiazepine partial inverse agonist (S
      8510) were studied in the Fischer 344 (F344) rat and B6C3F1 mouse to obtain
      information for the planning of carcinogenicity studies. Sprague-Dawley (SD) rats
      were also included for comparison. 2. Clear non-linear elimination of S-8510 was
      observed after single oral administration of S-8510 in all animals tested (F344
      rat, 1-50 mg/kg; SD rat and B6C3F1 mouse, 1-150 mg/kg). 3. Exposure of S-8510
      after single oral administration was in the order F344 rat > B6C3F1 mouse > SD
      rat. 4. Multiple oral administration to F344 rat and B6C3F1 mouse decreased the
      exposure to S-8510. 5. These results indicate that it is very important to
      evaluate pharmacological and toxicological studies based on exposure and to be
      careful in selecting the species and strains of animal used in toxicology
      studies.

PMID- 9622854
TI  - Effect of diet on the urinary excretion of hippuric acid and other dietary
      derived aromatics in rat. A complex interaction between diet, gut microflora and
      substrate specificity.
AB  - 1. A combined in vivo and in vitro study has been devised to investigate an
      observation, obtained by 1H NMR of urine, that Alp:AprSD (Wistar derived) rats
      kept under standard husbandry conditions did not excrete urinary hippuric acid
      (HA). meta-(hydroxyphenyl)-propionic acid ?m-HPPA? was identified as the major
      aromatic component in urine samples lacking HA. 2. Examination of urine from
      Alp:APrSD and Zucker (obese negative) rats fed various diets showed that the lack
      of HA/presence of m-HPPA was due to diet and not to the strain of animal. This
      observation was reinforced by the demonstration that the administration of
      benzoic acid (BA) to rats not previously excreting urinary HA resulted in the
      return of this component to the urinary excretion profile. Thus rats receiving
      the standard diet were still capable of glycine conjugation. 3. Changing the diet
      of rats excreting m-HPPA led to the cessation of m-HPPA excretion and the return
      of HA urine excretion. Interestingly, switching back to the original diet did not
      cause the loss of HA and the re-emergence of m-HPPA. 4. In vitro studies on the
      two enzyme systems responsible for glycine conjugation (benzoyl CoA:synthetase
      and benzoyl CoA:glycine N-acyltransferase) in isolated liver mitochondria showed
      that m-HPPA did not inhibit either enzyme. However, m-HPPA was not found to be a
      substrate for the first reaction step explaining why it was found in the urine as
      the free acid and not as a glycine conjugate. 5. The absence and presence of m
      HPPA and hippuric acid is suggested to be due to a combination of differences in
      dietary precursors of substrates for glycine conjugation and a dietary dependent
      redistribution of the intestinal microflora responsible for breakdown of plant
      phenolics and aromatic amino acids. Taken collectively this study emphasises how
      a simple diet change can cause a profound change in metabolism.

PMID- 9622855
TI  - [Prof. Dr. Dr. h.c. Helmut Wolff].

PMID- 9622856
TI  - [Improved hepatic duct drainage. 1912].

PMID- 9622857
TI  - [Hans Kehr, the surgeon].

PMID- 9622858
TI  - [Prof. Hans Kehr--his life and his work].

PMID- 9622859
TI  - [Anesthesiologic retrospective view of the surgeon Hans Kehr].
AB  - Prof. Hans Kehr's contributions to the development of operative procedures for
      the treatment of gall bladder and bile duct diseases at the end of the 19th and
      the beginning of the 20th century are unquestionable. An anaesthesiological look
      back at Kehr demonstrates, that this vivacious surgeon drew his attentions also
      to the perioperative care of his patients and to the choice and administration of
      adequate anaesthesiological procedures. Already in 1896 in his report to the
      Annual German Surgical Congress he mentioned anaesthesiological aspects. In his
      main book publications ("Technique of gall-stone operations"; 1905 respectively
      "Practice of bileduct surgery"; 1913) there are special chapters on "Anaesthesia
      in gallstone operations resp. Anaesthesia in bile duct surgery". Some of Kehr's
      statements, published here, seem to be accurate even today, for example these
      from 1913: "Adequate anaesthesia is nearly more valuable than the best surgical
      technique and the most skillful assistance". "... it is clear for me, that a good
      anaesthetist remarkably improves the results of an operation, while a bad one
      deteriorates them."

PMID- 9622860
TI  - [Retrospective view of the development of surgical therapy of gallstones].
AB  - This paper gives a short historical overview of the evolution of biliary surgery
      from John Stough Bobbs (1867) until the present day. The development of different
      diagnostic methods (from cholangiography to sonography) are described also, as
      well as the different therapeutic methods including laparoscopic cholecystectomy.
      Hans Kehr (1862-1916) was a distinguished pioneer in the development of biliary
      surgery.

PMID- 9622861
TI  - [Indications for surgical therapy of gallstones].
AB  - 4675 patients which underwent a cholecystectomy because of gallstone disease were
      included in a prospective multi-institutional study from 01/09/1994 to 31/08/1995
      at 29 east-german hospitals. 3,207 (68.6%) patients had done a laparoscopic
      cholecystectomy (LCE). 1,468 (31.4%) patients received a primary open
      cholecystectomy (KCE). A conversion rate of 7.7% (n = 247) was seen. In 32.8% of
      LCE and in 39.5% of KCE diagnostic procedures of the common bile duct were not
      performed at all. The rate of open revision of the common bile duct was 4.5% (n =
      211). The highest postoperative morbidity and operative mortality were found in
      KCE with revision of the common bile dutct.

PMID- 9622862
TI  - [Current surgical treatment status of gallstones in East Germany].
AB  - The changes of surgical treatment of gallstone disease to the laparoscopic
      procedure was performed just at the same time in East Germany was destroyed the
      socialism. That's why the new operative technique was possible in many hospitals
      in 1992/93 first. To describe the actually situation and the trend we started a
      prospective multi-institutional study included 29 East German surgical
      departments of all kinds. The most interesting things were perioperative
      antibiotic prophylaxis, laparoscopically procedures in elderly or high risc
      patients, the management of common bile duct stones and the minor and major
      complications. We discuss the results and the comparison with the results of
      externe quality assurance.

PMID- 9622863
TI  - [Aspects of preoperative management of biliary surgical procedures].
AB  - Difference between open cholecystectomy and laparoscopic cholecystectomy are
      described. General preparations and pre-operative work up in Austria,
      Switzerland, Germany and East German quality assurance study at compared. The
      importance of antibiotic and thrombembolic prophylaxis increased.

PMID- 9622864
TI  - [Preoperative diagnosis in laparoscopic cholecystectomy: is intravenous
      cholangiography currently still justified?].
AB  - Laparocopic cholecystectomy requires essentially the safe exclusion of
      choledocholithias. The aim of this study was to compare the intravenous
      cholangiography and ERCP in addition to a basic program (case history, laboratory
      results ultrasound) with references to the diagnostic ability and therapeutic
      consequences in patients with choledocholithiasis. The results show, that the
      intravenous cholangiography not provides extra important informations after the
      case history, ultrasound and laboratory findings and therefore its general use is
      not justified. Instead of the intravenous cholangiography the preoperative ERCP
      should be performed generously if choledocholithiasis is suspected, especially
      because the ERCP offers the possibility to extract the stone.

PMID- 9622865
TI  - [Antibiotic prophylaxis in cholecystectomy--necessary and cost saving?].
AB  - The effectiveness of antimicrobial prophylaxis was evaluated on the basis of data
      collected in a study on quality management carried out in 28 East German
      hospitals, involving 4477 laparoscopic and conventional cholecystectomies (197 of
      which with revision of the common bile duct). In 3128 patients a laparoscopic
      procedure (with consecutive conversion to an open cholecystectomy in 236 cases)
      and in 1349 patients a primarily conventional open cholecystectomy had been
      performed (a total of 2217 cases with and 2260 cases without antibiotic cover).
      The results obtained were significantly better in the group receiving prophylaxis
      than in patients not under antimicrobial cover. This applied to septic wound
      healing disorders, general and specific postoperative complications,
      postoperative chest infections, re-operations and postoperative lethality. On the
      basis of these results, it is strongly recommended that, in the future, neither
      laparoscopic nor open conventional cholecystectomy should be carried out without
      proper perioperative antimicrobial prophylaxis-this all the more so since such
      measures also result in a shorter hospital stay and thus reduced costs.

PMID- 9622866
TI  - [Surgical therapy of choledocholithiasis].
AB  - Following the introduction of endoscopic papillotomy and stone extraction,
      surgical bile duct revision has decreased considerably in importance during the
      past two decades. Surgical bile duct revision is associated with an appreciably
      higher rate of complications than endoscopic stone extraction. The result has
      been that most working groups now favour a "therapeutic splitting" approach. This
      means that, wherever possible, endoscopic revision of the bile duct is first
      attempted. If, during laparoscopic cholecystectomy, intraoperative
      cholangiography reveals the presence of bile duct stones, they may, after
      consultation with the endoscopist, be left in place for removal by endoscopic
      papillotomy at some later date. Only in the case of very young patients and
      exceptionally, a highly experienced laparoscopic surgeon may attempt a
      transcystic extraction of such stones. Continuing indications for conventional
      surgical treatment of choledocholithiasis are local factors obstructing access to
      the papilla (gastrectomy, stenosis of the pylorus) and other bile duct changes
      requiring correction (choledochocele, strictures, stenoses, Mirizzi's syndrome,
      over-looked impacted stone obstructing an over-long cystic duct stump,
      intrahepatic lithiasis).

PMID- 9622867
TI  - [Value and technique of laparoscopic choledochus revision in
      choledocholithiasis].
AB  - Despite a large scale indication to ERCP, 5% of unsuspected stones are shown by
      principally intraoperative cholangiography in our patients. Praeoperative
      diagnostic makes it possible to select the individual optimal therapy for each
      patient, the possibility of saving the Papilla vateri gives the large scale
      indication to laparoscopic common bile duct exploration. Also suspected stones
      gets a one-time cure therapy by complete laparoscopic operation. After balloon
      dilatation of cysticus duct to 6 mm, the laparoscopic choledochoscopy is possible
      through the cysticus duct. Little stones are flushed into the duodenum or
      extracted by Segura-basket through the cysticus duct. Big stones needs a Laser-
      or electrohydraulic lithotripsy, the stonefragments can be flushed into the
      duodenum or aspirated through the cysticus duct. Multiple big or proximal
      incarcerated stones gives the indication for laparoscopic choledochotomy.
      Effective extraction is possible by big Segura-basket, residual stones are taken
      out under choledochoscopic control by little Segura-basket. Incarcerated stones
      needs the lithotripsy. Microdrainage of the common bile duct and only in special
      indication the T-tube saves the gall-flow to restitution of papilla function, the
      common bile duct is closed by running suture in Lahodny-technique. After the
      regular postoperative cholangiography on third day after operation, the
      microdrainage can be taken out. In 96% of all laparoscopic cholecystectomies the
      intraoperative cholangiography was successful. Only 3 of 103 patients needs a
      postoperative EPT because of residual fragments after trans cystic duct
      exploration. 8 laparoscopic choledochotomies shows the successness of endoscopic
      techniques, the postoperative complications can be the same then in conventional
      operation.

PMID- 9622868
TI  - [Therapy of common bile duct calculi--therapeutic change with success? Results of
      the CESAQ Study 1994/1995 and the medical and surgical department of the Berlin
      Friedrichshain Hospital].

PMID- 9622869
TI  - [Endoscopic treatment of choledocholithiasis at the Suhl Clinic 1 November 1994-1
      December 1996].

PMID- 9622870
TI  - [Endoscopic therapy of cholangiolithiasis by percutaneous approach. Percutaneous
      gallstone therapy].
AB  - PATIENTS AND METHODS: In a retrospective study, the results of percutaneous
      transhepatic therapy of bile duct stones under cholangioscopic control (PTCS)
      were evaluated in 32 patients in which a endoscopic retrograde stone removal was
      impossible or failed. RESULTS: Previous gastric surgery was the most common
      reason for choosing the percutaneous route (22 cases). Five patients had
      biliodigestive anastomosis, two pyloric obstructions, and in three patients the
      retrograde stone removal failed. Complete stone removal was obtained after 3 to
      11 (median 5) percutaneous procedures in all cases, in 28 patients by
      electrohydraulic lithotripsy, and in the remaining 5 cases by mechanical
      extraction alone. There was no complication due to cholangioscopy and lithotripsy
      themselves. Two cases had major complications which needed laparotomy (4%, one
      case had capsular bleeding from the liver, another one had catheter perforation
      of the duodenum). In addition, three cases (7%) had minor complications which
      required no therapy during the percutaneous fistula procedure. Two elderly
      multimorbid patients (4%) died during hospitalisation after successful stone
      removal not related to the performed procedure. CONCLUSION: The percutaneous
      transhepatic cholangioscopy (PTCS) and lithotripsy are highly effective
      techniques for endoscopic treatment of bile duct stones. Because of an increased
      rate of complications during the fistula procedures, both methods should be
      restricted to cases with difficult anatomic situation and high risk of surgery.

PMID- 9622871
TI  - [Experiences with different lithotripsy methods in the primary endoscopic
      transpapillary non-extractable gallstone].

PMID- 9622872
TI  - [Endoscopic diagnosis and therapy of cholecysto- and choledocholithiasis].
AB  - Not only for systematical reasons a differentiation of gallstones disease between
      cholecystolithiasis and choledocholithiasis is sensible. Although the two
      diseases are basically caused by gallstones, they generally differ in diagnostic
      and therapeutic strategies. While the cholecystolithiasis is the domain of
      visceral surgeons and today almost exclusively and definitively cured by
      microinvasive cholecystectomy, for the treatment of choledocholithias there are
      required the endoscopic procedures of physicians.

PMID- 9622873
TI  - [Therapy of acute cholecystitis from the surgical viewpoint].
AB  - The over notion, "acute gallbladder" includes the acute cholecystitis, also the
      gallbladder dropsy, the persistent colicky pain of the impaction, the
      complications of acute cholecystitis like the cholecystoempyema an necrotising
      the calculous impaction inflammation. In the last cases an emergency operation
      ist necessary. The acute cholecystitis and also the acute gallbladder dropsy have
      to be operated in an unit of time of 72 hours. By this patients the capability of
      operation and narcosis is a prerequisite. The late operation also the interval
      operation are united with greater operative technical difficulties an the danger
      of intraoperative complications. The indication for the cholecystostomy ist rare.
      Is an anaesthesia not possible a surgical stomy in local anaesthesia or a
      percutaneous transhepatic puncture drainage with sonography and CT-control ist
      possible. There are scarcely contra-indications for the laparoscopy.

PMID- 9622874
TI  - [Laparoscopic cholecystectomy as routine intervention in acute cholecystitis].
AB  - The laparoscopic cholecystectomy has become the gold standard in the therapy of
      gall bladder stones in the last few years. The most contraindications of the
      first period of the laparoscopic era had been eliminated by the development of
      laparoscopic technique and growing experience. Since September 1995 the
      laparoscopic cholecystectomy has been established as routine procedure also for
      acute cholecystitis. From September 1995 to Dezember 1996 177 laparoscopic
      cholecystectomies were performed, 132 for symptomatic cholecystolithiasis and 45
      for acute cholecystitis. Postoperative complications occurred in 8.3% in the
      elective group and in 8.8% in the acute cholecystitis group. There was no death
      in both groups. Patients left the hospital on day 3 (range 2-21) in the elective
      group, on day 4 (1-13) in the acute colecystitis group. There are no
      statistically significant differences. According to our results acute
      cholecystitis does not increase postoperative morbidity and mortality after
      laparoscopic cholecystectomy and has to be a contraindication for this method no
      longer.

PMID- 9622875
TI  - [Recurrent gallstone ileus--enterolithotomy alone or synchronous complete
      management].

PMID- 9622876
TI  - [Gallbladder carcinoma--an unexpected finding after laparoscopic
      cholecystectomy].
AB  - The carcinoma of the gallbladder can be found mostly in a late stage. We have to
      expect a incidental carcinoma of the gallbladder in 1-2% after conventional
      cholecystectomy. We report 9 cases of unexpected carcinoma of the gallbladder
      after 1700 laparoscopic cholecystectomies. The time of survival were--dependent
      on tumor stage--2 to 36 month. We outline special items of this disease within
      the context of minimal-invasiv surgery.

PMID- 9622877
TI  - [Possibilities and limits of invasive endoscopy in treatment of endoscopic
      surgical complications after operations of the biliary tract].
AB  - Minimal invasive methods compete with surgical treatment in the therapy of
      complications after cholecystectomy. We demonstrate our results of endoscopic
      therapy. 52 patients with postoperative complications (39 stenoses, 5 leakages, 6
      stenoses and leakages, 2 complete obliterations of bile duct) were treated by
      transpapillary or transhepatic biliary drainage over a time period of 12 months.
      In 73% of patients who completed the therapy protocol successful treatment was
      possible. In 4 cases a restenosis occurred. 4 patients underwent surgical
      treatment. We think endoscopic management is the therapy of first choice for
      postoperative biliary complications. Biliary stricture should be dilatated for 12
      months by biliary endoprosthesis, leakage can be drained for shorter time
      periods.

PMID- 9622878
TI  - [Value and sensitivity of abdominal ultrasound in preoperative histologic
      diagnosis before laparoscopic cholecystectomy].
AB  - In a retrospective study we compared the findings of our abdominal ultra-sound
      diagnostic of the gallbladder and the common bile duct with the results ot
      preoperative ERCP, intraoperative findings and the histological results. The test
      parameters were the size of the gallbladder, the number and the size of biliary
      calculi, the thickness and the constitution of the wall of the gallbladder and
      the consecutive grade of inflammation, the wideness of the common bile duct and
      the suspicion of a choledocholithiasis, respectively. In acute cholecystitis we
      performed laparoscopic cholecystectomy within 24 hours, in symtomatic
      cholecystolithiasis without cholecystitis an elective laparoscopic
      cholecystectomy. If there was suspicion of a choledocholithiasis we performed a
      preoperative ERCP. Altogether we had correct findings of the common bile duct in
      our ultrasound diagnostic in 133 of 136 cases (97.8%), only in 3 of 136 cases
      (2.2%) we had false negative ultrasound findings. With a generous indication to
      ERCP caused by anamnestic and/or laboratory findings the obstruction of the bile
      duct could be diagnosted and eliminated in 2 of these 3 cases preoperatively. In
      all cases of bile duct dilatation (7 mm and more) we found an obstruction of the
      common bile duct. Our results demonstrate that abdominal ultrasound is a high
      efficiency method in the preoperative diagnostic of gallbladder and common bile
      duct stones.

PMID- 9622879
TI  - [Early and late outcome of biliodigestive anastomosis and transduodenal
      papillotomy in benign diseases of the bile ducts].
AB  - The results of a prospective study of 188 choledochoduodenostomies, 51 choledocho
      jejunostomies, and 114 transduodenal papillotomies in patients with benign
      diseases are presented. The operations were performed between 1974 and 1997. The
      status of the patients was checked every one to two years. During the same time
      period a total of 5128 patients with benign disorders of the gall bladder or
      biliary tract was operated upon. In consequence to the important progress of
      endoscopic diagnostic and therapeutic options indications and methods of biliary
      surgery have changed significantly. Open procedures at the choledochal duct,
      biliodigestive anastomoses, and transduodenal papillotomies are recently
      performed only in rare instances.

PMID- 9622880
TI  - [Diagnosis and therapy of biliary complications after laparoscopic
      cholecystectomy by ERCP].
AB  - Biliary tract injury, although uncommon, is the most feared complication of
      laparoscopic cholecystectomy. Early identification or exclusion of such injury is
      essential for successful management. Over a two year period (1995-1996) twenty
      one from a total of 413 ERCPs in this Surgical Endoscopy Unit were performed
      because of suspected biliary injury after laparoscopic cholecystectomy. 16
      patients were referred from other units. No abnormality was demonstrated in two
      cases. A clip-related stenosis requiring reoperation was shown in twei patients.
      The remaining 17 cases had biliary leakage, related to an aberrant bile duct in 2
      cases or a cystic duct leak in 15, all of which were treated endoscopically by
      nasobiliary tube (7), endoscopic papillotomy (5) or a combination of both (5).
      All of these biliary leaks healed uneventfully no ERCP-associated morbidity.

PMID- 9622881
TI  - [Endoscopic interventions of the biliary tract in postoperative complications
      after cholecystectomy for preventing relaparotomy].
AB  - The postoperative complication rate of laparoscopic cholecystectomy (LC) is about
      5-6%. The most frequent complications are residual gallstones in the common bile
      duct, biliary leckage, biliary fistula and duct stenosis. In the period between
      01.11.94 and 01.04.96 we performed 1620 endoscopic retrograde cholangio
      pancreatographies including 410 papillotomies at the second Department of
      Medicine in the Clinic of Suhl. Thereby in 2.1% (34 cases) of patients a
      complication after laparosopic cholecystectomy was seen and endoscopically
      controlled. Residual bile duct stones were removed without any problems by
      papillotomy and stone extraction. Biliary leckage were brigded by stent
      implantation. In case of aberrant cystic duct it was also possible to implant a
      stent depending on anatomical situation. All patients were followed up over a
      period of 6 to 8 month after endoscopic procedure. All except two patients showed
      an occlusion of biliary leckage and the bile duct stent could be revved. In one
      case, a younger patient, with a failed endoscopic occlusion of biliary fistula
      had to undergo a further operation because of residual gallbladder tissue. In the
      other case, a 84-years old patient, we use a new method, developed at our
      department, for selective embolization of the cystic duct to prevent a
      relaparotomy. The leckage was sufficiently closed. Endoscopic intervention is
      indicated in case of postoperative complication after LC and successful in the
      majority of cases. This should primarily discussed between surgeon and physician.
      Only secondarily a relaparotomy should be performed, if endoscopic procedures
      have failed.

PMID- 9622882
TI  - [Dislocation of clips of the cystic duct stump].
AB  - The security of six different laparoscopic clips was investigated using 60
      kryopreserved specimens of human cystic ducts. After fixation of the cystic duct
      the cross placed clips were distracted in axial direction and the maximum forces
      to remove the clip were registered. The mean dislocation-force was 4.6 Newton for
      titanium clips and 9.3 Newton for absorbable clips with a highly significant
      difference (p < 0.001, Wilcoxon-test). Additional to the advantage of complete
      biodegradibility these data favour the use of absorbable clips, because of a
      better hold force compared to titannium clips.

PMID- 9622883
TI  - [Endoscopic therapy of postoperative complications of the bile ducts].

PMID- 9622884
TI  - [Is in laparoscopic cholecystectomy a general medicamentous thromboembolism
      prophylaxis necessary?].

PMID- 9622885
TI  - [Interdisciplinary therapy of gallstones. Round table discussion].

PMID- 9622886
TI  - [Surgical tradition commemoration in East Germany].

PMID- 9622887
TI  - [Chronic inflammatory bowel diseases].

PMID- 9622888
TI  - [Standards, perspectives and limits of conservative therapy of chronic
      inflammatory bowel diseases].
AB  - Improvement and standardization of the conservative therapy of inflammatory bowel
      disease has lead to a better prognosis for the patients. During the acute flare
      of Crohn's disease steroids are still the standard therapy, whereas 5
      aminosalicylic acid (5-ASA) preparations are used for maintenance therapy during
      remission. In contrast ulcerative colitis may be treated with 5-ASA also for
      acute exacerbations. The development of new drugs as for example the topical
      steroids helps to improve life quality of the patients by reducing adverse side
      effects. Potent immunosuppressants as azathioprine and methotrexate are useful in
      chronic active and refractory disease. Cyclosporin A plays a role in severe
      steroid refractory colitis. In the future immunomodulation by application of
      antiinflammatory cytokines or antibodies to inflammatory cytokines may have its
      place in the treatment of IBD patients. In some cases, however, the conservative
      therapy reaches its limits. Mistakes in the therapy are made, when these limits
      are not recognized and complications are not discovered in time.

PMID- 9622889
TI  - [Necessary diagnosis before and reliable examinations after surgical
      interventions in chronic inflammatory bowel diseases].
AB  - The primary diagnosis of chronic inflammatory bowel disease (Crohn's disease,
      ulcerative colitis) is performed by standardized procedures in specialized
      Gastroenterology Departments or Ambulances. For the assessment of disease
      activity the clinical presentation of the patient is most important. This is also
      true for the indication for surgical interventions. In certain instances
      laboratory markers, endoscopic and histologic examinations, ultrasound, X-ray,
      and cross-sectional imaging like computed tomography (CT) or magnetic resonance
      imaging (MRI) give important additional informations. Depending on the clinical
      situation surgeons and gastroenterologists decide on the most useful technical
      examinations for planning the operative strategy. After surgery, diagnostic
      procedures focus on disease progression and complications. Disturbances of
      intestinal function as consequence of the operation have also to be considered in
      the routine diagnostic program.

PMID- 9622890
TI  - [Surgical concepts in Crohn disease of the terminal ileum and colon].
AB  - Most patients with Crohn's disease have to be operated on. Necessity to loose
      some amount of the intestine and time-point of the surgical intervention may be
      derived from the irreversible cascade of the inflammatory process and the
      limitations of the conservative treatment. In ileocecal disease indications for
      surgery are represented by stenotic and/or penetrating complications of the
      inflamed bowel, whereas in Crohn's colitis acute or terminal medical refractority
      is predominating. Standard-procedures result from constantly definable patterns
      of the disease manifestation: ileocecal resection and colectomy/-proctocolectomy.
      In segmental colitis sometimes "resections within Crohn's" may be adequate in a
      first attempt to avoid anticipating the natural course by surgical means. In
      these cases the further prognosis depends on the treatment possibilities of the
      remaining colon. In contrast, true recurrence is a new inflammation of the
      neoterminal ileum and may indicate repeated resections. The frequence decreases
      with the number of resections. Nevertheless nutritional status is restored even
      by multiple resections, whereas specific functional sequelae of the resection-
      distal resection- and dehydration syndromes--are well treatable mostly. In the
      case of appropriate timing of the operation and the reoperation operative
      morbidity and mortality are remarkable low today resulting in an almost normal
      life expectancy. Most important as negative prognostic factor remains sepsis
      resulting from pre-existing or postoperative infectious complications. Keeping
      this in mind experimental pharmaco-therapy to delay the operation and not
      profoundly substantiated tendencies to minimize surgery are to be considered only
      with critical scepticism. At the moment, future research is thought to be more
      successful in focussing prophylaxis of ileal recurrence than avoiding surgery.

PMID- 9622891
TI  - [Gastroduodenal involvement and circumscribed intestinal stricture in Crohn
      disease].
AB  - Symptomatic gastroduodenal Crohn's disease (CD) is rare although new
      endoscopic/histologic data indicate a typical focally enhanced gastritis in up to
      half of all patients with CD. One third of the patients with symptomatic
      gastroduodenal CD undergo surgery, most of them for (gastro-) duodenal
      obstruction. Gastroenterostomy with vagotomy is the surgical treatment of choice.
      Resection, strictureplasty or balloon dilatation can be performed in selected
      patients. Enterogastric and enteroduodenal fistulas are rare, frequently missed
      during routine examination and often detected only during laparotomy. Treatment
      of those fistulas consists of resection of distal bowel (fistula origin) with
      suture closure of the fistula opening in the stomach/duodenum. Recurrence rate
      after surgery for gastroduodenal CD is lower than in ileal and/or colonic
      disease, and only a minority of the patients requires further surgical
      intervention. Bowel obstruction is a frequent indication for surgery in CD.
      Interventional or surgical therapy should be performed in chronic-recurrent
      obstruction, progressive stenosis and stenosis refractory to medical treatment.
      In short fibrous stenosis of the small bowel or ileocecal anastomosis without
      acute inflammation or perforating complications balloon dilatation or, if
      endoscopic access is not possible, strictureplasty should be performed. In all
      other cases, especially in colonic strictures with their increased risk of
      malignancy, resection is the treatment of choice. The results of balloon
      dilatation, strictureplasty or resection are comparable with five year
      reoperation rates reported between 20% and 38%.

PMID- 9622892
TI  - [Surgical treatment of Crohn disease based on the inflammatory pattern].
AB  - 286 patients with Crohn's disease were classified on the basis of the
      inflammatory pattern at their first operation as type 1 (Ileitis: n = 116), type
      2a (segmental colitis: n = 60), and type 2b (total colitis: n = 108); 2 patients
      remained unclassified. At the same age at operation of 31.9 +/- 10.7 yrs symptoms
      were known in type 1 for 3.4 +/- 3.9 yrs, but for 7.5 +/- 5.7 yrs in type 2b.
      Main indication in type 1 was stenosis (56.9%), whereas in type 2b
      intractabilitiy (68.5%) predominated. Type 2a was intermediate concerning
      duration of symptoms and relationship of indications including fistulas. Standard
      procedures were ileocecal resection (92.2%) in type 1, and colectomy (90.7%) in
      type 2b. In type 2a ileocolic resections and partial colectomies were mostly
      done. During the following 3.9 +/- 3.8 yrs reoperation rate due to disease
      progression was 13.6% in type 1, 25.5% in type 2a and 18.5% in type 2b. The
      cumulative risk of ileal resection at ten years due to new inflammation was
      significantly (p < 0.01) higher in the case of ileocolic/ileorectal anastomosis
      than of ileostomy (38% vs. 11%). In contrast, cumulative probability of a
      colorectal resection was significantly (p < 0.05) higher in type 2 (16%) when
      compared to type 1 (1.5%). Primary ileal loss was significantly (p < 0.01) higher
      in type 1 (37 +/- 23 cm) compared with type 2a (25 +/- 28 cm) and type 2b (17 +/-
      21 cm). Loss of continence occurred in 0%, 3.3% and 53.7% respectively. With
      reoperations additional loss of ileum decreased in all types, whereas in type 2
      loss of anorectal function increased. Including reoperations the rate of major
      complications was 9.8% and lethality was 0.8% (3/386). Resections in Crohn's
      disease are unavoidable due to shrinking therapeutical alternatives in the course
      of the disease. Owing to limited resections, loss of bowel may not exceed ileum
      in type 1, whereas the same resectional policy cannot avoid the total loss of the
      colorectum eventually in type 2. Both limited surgery and repeated resections
      help to maintain function as long as possible. Due to the high safety-standard
      the number of operations does not impair the success of the surgical concept.

PMID- 9622893
TI  - [Drug prevention of Crohn disease recurrence in the neo-terminal ileum after
      ileocolic resection].
AB  - Crohn's recurrence is the appearance of objective signs defined radiologically,
      endoscopically or pathologically of Crohn's disease in the bowel of a patient who
      has previously had a resection of all macroscopically diseased tissue. New
      lesions can be visualized endoscopically within weeks to months after ileal
      resection and ileocolonic anastomosis in the neoterminal ileum. The evolution of
      these lesions mimics the natural history of ileal Crohn's disease at the onset.
      If we are able to prevent recurrence of early lesions we would probably interrupt
      the natural course of the disease. The drugs tested until today include different
      5-ASA formulations, metronidazole and budesonide. 5-ASA seems to have a limited
      protective effect. High dose metronidazole started immediately after surgery
      decreases endoscopic and symptomatic recurrence rates but is associated with a
      lot of side effects. Budesonide 6 mg/day o.m. reduces endoscopic recurrence after
      one year only in patients operated upon for inflammatory activity. Studies with
      immunosuppression for recurrence prevention are currently underway. Thus, today 5
      ASA-formulations are recommended as general pharmaco-prophylaxis.

PMID- 9622894
TI  - [Laparoscopically assisted surgery in Crohn disease].
AB  - From Jan. 1993 to Apr. 1997 intestinal resections in Crohn's disease have been
      performed in 275 patients. 89 patients have been operated on laparoscopic
      assisted. The following parameters were analyzed: previous laparotomies, extent
      of resection, steroid medication, conversionrate, complications, operative time
      and postoperative stay. Endpoints were: conversionrate, complications,
      reconvalescence and overall satisfaction with the laparoscopic technique.
      RESULTS: The duration of the disease ranged from 1 to 16 years (x = 6). 47
      patients were under steroid medication at the time of surgery. 30 patients had
      undergone previous laparotomies. In 10 patients the operation had to be converted
      into open surgery. The following procedures have been performed: ileocaecal
      resections (45), anastomotic resections (14), small bowel resections (4),
      hemicolectomies (12), colectomies (9), loopileostomies (4), adhesiolysis (1).
      Minor complications occurred in 6.7% of patients, major complications in 5.6%.
      Operative time ranged from 70 to 420 minutes (x = 173.7). The postoperative
      hospital stay was 13.3 days in the average. CONCLUSION: The morbidity of 12.3% is
      not higher than in open surgery. When complications do not occur the patients
      benefit from early convalescence, better cosmetics and shorter hospital stay.

PMID- 9622895
TI  - [Surgical management of anorectal complications in Crohn disease].
AB  - Anorectal manifestations can be expected in about 40% of all patients suffering
      from Crohn's disease. The frequency increases with extension of disease towards
      the anal canal. If the rectum is involved, they are obligatory present and
      contribute to the necessity of a stoma formation. Surgical indication is mostly
      given, especially in cases with putrid secretion. Primary aim of therapy is the
      control of peri-anorectal infection by excision of all the inflamed extramural
      tissue. Wether the underlying fistulas are excised too, depends on their
      topography to the sphincter system. Fistulas, running distal of the midth of the
      spincter, are radically excisebal and will definitely heal in over 90%. More than
      60% of all fistulous anorectal manifestations belong to this type. Rectovaginal
      fistulas are provided with fistuloplasty, however healing conditions are
      problematous and healing will only be gained in about 50%. Fistulas in the upper
      third of the sphincter or above the sphincteric plane (rectal fistula) are
      managed by seton drainage of the transmural tract and complete excision of the
      infected tissue around, so that disease is reduced to its most simply condition.
      The further aim then is to derive it to cicatrous concretisation, so that
      infection will not expand again and patients will be free of pain. However this
      needs prolongation of seton drainage for at least 6 to 12 months.

PMID- 9622896
TI  - [Surgical options in ulcerative colitis].
AB  - Surgery is needed in every second patient with pancolitis. Historically four
      surgical options have been developed: conventional ileostomy, ileorectostomy,
      continent ileostomy (Kock's pouch) and ileo-anal pouch. However, in emergent or
      unclear situations subtotal colectomy, ileostomy and preservation of the rectum
      is the most suitable operation. After recovery and in elective indications
      proctectomy and proctocolectomy establish the general surgical standard. Today,
      in most cases ileo-pouch-anal anastomosis is performed instead of creation of an
      ileostomy. Both lowered frequency of defecation and acceptable continence
      contribute to a better quality of life. However, functional disturbances are not
      uncommon and result in most cases from complications of the demanding technique.
      Definitive cure of the colitis is in interference with the risk of pouchitis in
      about 30%. The cumulative probability to loose the pouch may rise to 15-20% in
      the long-term course. Thus, ileorectostomy may be considered as a first step of
      surgical treatment, since pelvic nerve damage is excluded, function is much
      better and persistent proctitis can be treated topically. The attractively is
      that ileo-anal pouch can be performed later on, when decreasing function and
      increasing risk of malignant change will eventually require proctectomy. A Kock
      pouch is seldom considered, especially in patients with ileostomy wishing sure
      fecal control. But the continent reservoir becomes more and more interesting
      again since it can be reconstructed from a failed ileo-anal pouch without loss of
      bowel. Conventional ileostomy should be reserved for patients not suitable for
      reconstructive methods or those who consider pough operations risk. However, it
      is the safest procedure with absolute cure of disease. The optimal choice of
      method considers medical and surgical aspects as well as patients conception and
      desire.

PMID- 9622897
TI  - [Technique and results of ileoanal pouches in ulcerative colitis after colectomy
      and proctomucosectomy].
AB  - The continence preserving restorative proctocolectomy is the operation of choice
      for ulcerative colitis. Many technical aspects of the J-pouch procedure have been
      standardised. We prefer the hand-sewn pouch-anal anastomoses and construct a
      protective ileostomy in most patients. Latter allows to carefully assess the
      sphincter function postoperatively and--if necessary--to train the sphincter
      before restoring continence. The frequency of postoperative ileus is comparable
      to that after other major intraabdominal surgery. Septic pelvic complications
      occur in up to 10% of patients and determine the long-term prognosis of pouch
      function. Following pouch reconstruction, the stool frequency remains increased
      (4-6 per day) and continence may be partially impaired especially at night. These
      consequences are accepted by most patients. Because the ileoanal pouch procedure
      is a difficult and complicated operation, it should be performed by experienced
      surgeons only.

PMID- 9622898
TI  - [Direct ileum pouch-anal anastomosis in ulcerative colitis: function and
      complications after stapler technique].
AB  - Stapled ileal pouch-anal anastomosis after proctocolectomy enables a continence
      preserving reconstruction. We assessed complications and functional outcome after
      ileoanal pouch-anastomosis in 86 consecutive patients with ulcerative colitis.
      There was no postoperative mortality. 2 patients required permanent ileostomy and
      pouch excision for manifestation of unsuspected Crohn's disease. Major
      postoperative complications consisted of pelvic sepsis (n = 2), anastomotic
      leakage (n = 4), bleeding (n = 1), pancreatitis (n = 3) and peritonitis (n = 1).
      Both frequencies of bowel movements and degree of continence improved with time.
      Two years after take down of the deviation ileostomy frequency of bowel movements
      was 5,6 [2]/die. At this time no patient complained of major incontinence. Minor
      incontinence was reported with 9% and 14% during day-time and night-time
      respectively. It is concluded that direct stapled ileal pouch-anal anastomosis is
      a safe procedure with excellent functional results for patients with ulcerative
      colitis.

PMID- 9622899
TI  - [Changes in colitis surgery. I: Is there a standard in primary surgical
      treatment?].
AB  - In a 15 years period surgery of ulcerative colitis expanded from ileostomy (IS)
      via Kock's pouch (KP) and ileoanal pouch (IAP) to ileorectal anastomosis (IRA).
      Interactions between availability of methods and frequency of operations are
      investigated retrospectively in order to establish an optimal primary procedure.
      With an overall amount of 80 operations the yearly operative frequency raised in
      correlation to the introduction of continence reconstructive procedures. As a
      consequence of this fact history of disease was shortened to less than 8 year and
      global colitis-associated morbidity markedly decreased. For patients readiness to
      undergo operation Kock's pouch was only important at the beginning (n = 9/11.3%).
      Most decisive was IAP (n = 49/61.3%) which could be realized last even in an one
      stage-procedure with better early results due to improved patients conditions and
      simplified technical modifications. IRA (n = 7/8.8%) played only a limited role
      in the last years for selected patients, whereas IS (n = 15/18.8%) kept reserved
      for contraindications to reconstructive surgery. For all procedures operative
      complications decreased from 46.1% (12/26) to 11.0% (6/54) and lethality to 0%.
      Late complications were related to proctectomy (nerve damage) and construction of
      IAP (pouchitis in 34.8% and defunctioning of the pouch in 10.4%), whereas IRA was
      free of specific morbidity so far. Surgery of ulcerative colitis is characterized
      today by restoration of anal continence. The advantage of the changed surgical
      concept lies within the ability to perform colectomy at an earlier stage of the
      disease. Safe construction of IAP is the most important technical progress. Early
      operation of colitis and late morbidity of pouch justify (preliminary) IRA. Thus,
      surgical standard in colitis-surgery is defined more individually.

PMID- 9622900
TI  - [Changes in colitis surgery. II: Corrective interventions and conversion
      operations].
AB  - Over a period of 9 years in 48 patients already operated on for ulcerative
      colitis secondary surgical interventions had to be planned. 25 patients had an
      ileostomy (IS), 10 a Kock-pouch (KP), 11 an ileoanal pouch (IAP) and 2 an
      ileorectal anastomosis (IRA). Whereas in 4 patients only the subjective wish for
      another procedure with better quality of life predominated, in 44 patients
      (91.7%) also objective, sometimes multiple indications for reoperation existed.
      In 37 patients main indications were complications or dysfunctions of the
      preexisting procedures, combined with the need for further resection of the
      colitis in 6 of them. Resection of the residual colitis was the main indication
      in the remaining 7 patients. The aim of the reoperation in all patients was both
      complete elimination of the eventually persisting colitis and restoration of
      quality of life in the best way wished or possible. Our of 25 IS 3 remained, 3
      were reconstructed, 17 were converted to KP and 2 to IAP. Out of 10 KP one
      remained and in 9 corrective surgery of the nipple valve was performed. Out of 11
      IAP 2 had to be resected with construction of IS, 5 were converted to KP and 4
      were corrected. Two IRA were converted to IAP. The rate of early complications
      was 8.3% (n = 4), lethality was zero. Late complications occurred in 13 cases
      (27.1%) and were associated ten times with KP. Complications of KP decreased with
      time to zero due to technical modifications. They could always be corrected
      restoring function. Since only one KP had to be resected due to severe pouchitis,
      KP was an important secondary procedure for 31 out of 48 patients also in the
      long-term course ensuring both complete elimination of colitis and good quality
      of life owing to voluntary fecal control.

PMID- 9622901
TI  - [Laparoscopically-assisted proctocolectomy with ileoanal pouch in ulcerative
      colitis].
AB  - Laparoscopic assisted proctocolectomy with ileoanal pouch is a technical
      alternative to the conventional open procedure. The aim of this technique are
      better cosmetics. Mobilisation of the colon is achieved laparoscopically. Rectal
      resection, J-pouch creation, and pouchanal anastomosis are performed via a
      Pfannenstiel incision. Laparoscopic assisted proctocolectomy has been performed
      in five selected patients, three female and two male aged 17 to 36 years.
      Operative time ranged from 305 to 420 minutes. Intra- and postoperative
      complications were not encountered. Postoperative hospital stay ranged from 13 to
      16 days. On a scale from 1 to 10 the average quality of life was graded 9 and the
      overall satisfaction level with the results of surgery scored 10. Function was
      identical to open surgery in not selected patients.

PMID- 9622902
TI  - [Thoracoscopic resection of epiphrenic esophageal diverticula by an
      intracavitary/endoluminal combined intervention].
AB  - Epiphrenic oesophageal diverticula are of the pulsation type, the underlying
      cause is a motility disorder. Resection is indicated by severe symptoms like
      dysphagia, regurgitation or aspiration and should be performed after endoscopic
      dilatative treatment of the neuromotor disturbance. Thoracoscopic resection under
      endoluminal endoscopic surveillance is considered to be a reliable procedure with
      low morbidity for the patient.

PMID- 9622903
TI  - [Restorative surgery of a Hartmann status for relief of chronic sphincter
      problems].
AB  - The Hartmann situation is a temporary intestinal diversion to treat diseases of
      the rectosigmoid. In case of benign rectosigmoidal disorders the entirely
      laparoscopic performance of the colon disconnection and reconstruction is an
      advantage due to its minimal invasive nature. A patient suffering from chronic
      anorectal fistula with temporary relief exclusively performed by laparoscopic
      approach is reported.

PMID- 9622904
TI  - [Electronic data processing in surgery--general practice, problems and
      prospects].

PMID- 9622907
TI  - Activity-based cost management. Part II: Applied to a respiratory protection
      program.
AB  - To demonstrate the relevance of activity-based cost management (ABCM) for the
      occupational and environmental health community, the investigators used data
      generated by an ABCM model of a respiratory protection program (RPP) to develop
      options for solving a business problem. The RPP manager in this hypothetical but
      realistic business scenario is faced with a 25% budget cut and a 10% increase in
      demand for RPP services. The manager's dilemma is to maintain the integrity of
      the RPP while absorbing a significant budget cut. Various cost savings options
      are developed, and the assumptions under which these options operate are
      presented. It is emphasized that the RPP manager's primary responsibility is to
      assure worker health and safety by first understanding the technical issues,
      merits, and implications of any cost-cutting option that may be considered. It is
      argued that only then should the manager consider the financial merits of the
      possible solutions to this business problem. In this way worker health and
      safety, and environmental protection goals, can continue to be achieved in an
      economic climate of cost cutting and downsizing.

PMID- 9622910
TI  - Rules and exemplars in category learning.
AB  - Psychological theories of categorization generally focus on either rule- or
      exemplar-based explanations. We present 2 experiments that show evidence of both
      rule induction and exemplar encoding as well as a connectionist model, ATRIUM,
      that specifies a mechanism for combining rule- and exemplar-based representation.
      In 2 experiments participants learned to classify items, most of which followed a
      simple rule, although there were a few frequently occurring exceptions.
      Experiment 1 examined how people extrapolate beyond the range of training.
      Experiment 2 examined the effect of instance frequency on generalization.
      Categorization behavior was well described by the model, in which exemplar
      representation is used for both rule and exception processing. A key element in
      correctly modeling these results was capturing the interaction between the rule-
      and exemplar-based representations by using shifts of attention between rules and
      exemplars.

PMID- 9622912
TI  - [Robotics and urology].

PMID- 9622911
TI  - Two separate verbal processing rates contributing to short-term memory span.
AB  - Previous research indicates that verbal memory span, the number of words people
      can remember and immediately repeat, is related to the fastest rate at which they
      can pronounce the words. This relation, in turn, has been attributed to a general
      or global rate of information processing that differs among individuals and
      changes with age. However, the experiments described in this article showed that
      the rates of 2 processes (rapid articulation and the retrieval of words from
      short-term memory) are related to memory span but not to each other. Memory span
      depends on a profile of processing rates in the brain, not only a global rate.
      Moreover, there appears to be only a partial overlap between the rate variables
      that change with age and those that differ among individuals.

PMID- 9622913
TI  - [Macroscopic and histologic analysis of the rat prostate after denervation].
AB  - OBJECTIVE: To determine the role of autonomic innervation in the preservation of
      the prostate gland structure, we analyzed the gross and histological features of
      the rat prostate submitted to denervation by resection of the pelvic ganglia.
      METHODS: The study comprised 80 male Sprague-Dawley rats aged 3 months; 42 were
      anesthetized and resection of the right pelvic ganglia was performed via
      laparotomy. Thirty days thereafter they were sacrificed. Gross and microscopic
      analyses of the right ventral lobe were performed. Computerized morphometric
      analyses of the areas occupied by the lumen, epithelial and stromal compartments,
      the height of the epithelium and the vascular pattern were performed. The results
      were compared with those obtained from the 38 ventral lobes of rats of the same
      age that had not undergone denervation. RESULTS: Gross examination of denervated
      rat ventral lobe demonstrated atrophy and weighted 36% less (p < 0.001).
      Histological analysis of the compartments showed 27.9% were epithelial, 48.3%
      stromal and 51.8% glandular--epithelial and lumen--for the control group versus
      14.8% (p < 0.001), 55.7% and 44.4% (not significant), respectively, for the
      denervated group. Denervated rat epithelial height measured 39.7% less. No
      differences in the vascular pattern were found. CONCLUSIONS: Resection of the rat
      pelvic ganglia, thereby inducing near-total vesico-prostatic denervation, causes
      structural and functional changes in the rat prostate compatible with atrophy.
      The observed changes were a reduction in weight and volume, as well as in the
      height and surface area of the secretory epithelium.

PMID- 9622914
TI  - [Suprarenal surgical pathology. Experience of 10 years and review of the
      literature].
AB  - OBJECTIVES: Our experience with 34 patients who underwent surgery of the adrenal
      gland over the last 10 years is presented. The most important clinical and
      pathological aspects are analyzed, particularly from the perspective of surgery,
      and the literature on the different pathologies observed in our series is
      reviewed. METHODS: A retrospective study was conducted to analyze the clinical
      features, analytical and hormonal data, imaging technique findings, types of
      anesthesia, surgical approaches, intra and postoperative morbidity and mortality,
      course of the disease, and pathological diagnosis. RESULTS: 53% were female. Mean
      age was 48.8 years. Left-sided involvement was more prevalent (70.7%). The most
      common pathology was adrenal adenoma (21 pts), followed by metastasis (4), cysts
      pseudocysts (4), primary carcinoma (2), pheochromocytoma (1), etc.
      Hyperaldosteronism (16 pts) was the most common hormonal disorder; 2 patients had
      Cushing's syndrome, 2 virilizing syndrome, 1 pheochromocytoma, and 13 patients
      had a nonfunctioning tumor (3 were incidentalomas). The mean size and weight were
      5.6 cm and 21.1 gm, respectively. Adenomas were the smallest tumors and those
      that weighed the least (mean 2.5 cm; 11.5 gm). Primary carcinomas were the
      largest tumors (mean 18 cm; 52 gm). US and CT were diagnostic in 56% and 100% of
      the cases and indicated the size of the mass correctly in 75% and 77%,
      respectively. Special anesthetic was required in 31%; nitroprusside,
      phenoxybenzamine, labetolol, corticosteroids and spironolactone were administered
      according to the hormone disorder. Lumbotomy via the 11th or 12th rib was the
      most common approach (58.7%), followed by the subcostal and transpleuro
      diaphragmatic approach (14.7%, 11.7%, respectively), etc. The mean operating time
      was 162.2 min; adenoma of the adrenal gland required the shortest operating time
      (133.06 min), while carcinoma of the adrenal gland required the longest (405
      min). Some type of intraoperative event arising from the hormonal disorder was
      observed in 44.2% of the patients. At 45.1 months mean follow-up, 70.5% of the
      patients were asymptomatic, arterial hypertension persisted in 11.7% and there
      were 5 deaths (all cases had a malignant tumor). CONCLUSIONS: The incidence of
      adrenal gland disease in our series is not unlike that reported in the
      literature. CT and complementary US are the diagnostic imaging techniques of
      choice. CT, moreover, has demonstrated a higher specificity. The surgical
      approach utilized was based on the pathological condition for which surgery had
      been indicated. The posterolateral and transpleurodiaphragmatic approaches were
      utilized for small tumors and no remarkable events were observed during the
      procedure. The anterior and combined approaches were utilized for large or
      bilateral tumors or obese patients. Our morbidity rate is not unlike that
      reported in the literature and basically depends on the chronic disease of the
      patient, type of hormonal disorder and size or malignant nature of the tumor.

PMID- 9622915
TI  - [Urothelial carcinoma of the upper urinary tract. Survival and prognostic
      factors].
AB  - OBJECTIVE: To analyze the survival and the main prognostic factors in patients
      with transitional cell carcinoma of the upper urinary tract. METHODS: From 1983
      to 1996, we treated 50 patients with transitional cell carcinoma of the upper
      urinary tract. Treatment was basically conservative except in those cases whose
      tumor stage or grade required a radical approach. Grading and staging were
      performed according to the 1992 TNM classification. Eighteen patients had died at
      one year mean follow-up., At the time the study was completed (June, 1997), 32
      patients were alive with a mean follow-up of 4.9 years. Disease-free survival,
      overall and specific survival were analyzed according to sex, age, association
      with bladder tumors, localization, type of treatment, tumor size, number,
      histological grade and stage. RESULTS: The male-to-female ratio was 5:1. Patient
      mean age was 65.7 years. Association with bladder tumors was observed in 50%.
      Treatment was conservative in 40% and radical in 60%. The five- and ten-year
      disease-free survival rates were 69%, overall survival 61% and specific survival
      71%. The univariate analysis showed the following to be unfavorable prognostic
      factors for survival: renal vs ureteral tumors, radical vs conservative
      treatment, high grade and stage tumors. The association of carcinoma in situ with
      other tumors of the upper urinary tract was also found to be an unfavorable
      factor for disease-free survival. The multivariate analysis associated T4 and G3
      tumors with poor prognosis. CONCLUSIONS: Transitional cell carcinoma of the upper
      urinary tract was associated with bladder tumors in 50% of the cases. Low grade
      stage tumors demonstrated a high survival rate, therefore conservative treatment
      should be the first approach. High grade/ stage tumors were found to be
      unfavorable prognostic factors for survival.

PMID- 9622916
TI  - [Non-urothelial neoplasm in patients with infiltrating bladder carcinoma].
AB  - OBJECTIVE: To analyze the incidence of non-urothelial neoplasms in patients with
      infiltrating bladder tumor submitted to radical surgery. METHODS: A retrospective
      study was conducted in patients who underwent radical cystoprostatectomy for an
      infiltrating bladder tumor from 1987-1996. The pathological and follow-up data
      were analyzed. RESULTS: Of 120 patients submitted to radical cystoprostatectomy
      for an infiltrating bladder tumor, 23 (19%) had an associated non-urothelial
      neoplasm: 14 (61%) were metachronous and 9 (39%) were synchronous. Two patients
      had two secondary tumors (9%). CONCLUSION: We have found a high incidence of non
      urothelial tumor in patients with infiltrating bladder tumor. By order of
      frequency, these were prostate cancer, gastrointestinal cancer, pulmonary cancer,
      etc. Studies have ascribed the association of prostate and bladder cancer to the
      deletion of suppressor genes.

PMID- 9622917
TI  - [Self-expanding metallic endoprosthesis in the treatment of recurrent ureteral
      stenosis].
AB  - OBJECTIVE: To describe two cases of recurrent fibrotic stricture of the uretero
      vesical junction treated with a metallic self-expanding endoprosthesis which has
      successfully achieved patency of the stenotic area in the medium-term. METHODS:
      Two cases of difficult ureteral stricture are described. Both cases presented
      obstruction of the terminal ureter by abundant fibrotic tissue in the bladder
      wall following radical prostatectomy in one case and TUR in the other for non
      infiltrating bladder carcinoma. Several attempts to recover patency by endoscopic
      resection and placement of a double-J stent in these patients had previously
      failed. The patients were therefore submitted to resection of the fibrotic area
      and insertion of a self-expanding endoprosthesis (Wallstent), which was
      eventually enclosed by fibrous tissue at its vesical portion. Both cases
      underwent resection again and another endoprosthesis (Memotherm) was inserted to
      extend the previous prosthesis 1 cm within the bladder lumen.
      RESULTS/CONCLUSIONS: When the endoprosthesis is placed in the uretero-vesical
      junction with its tip flush with the bladder wall, it is eventually enclosed by
      fibrous tissue, which invariably leads to recurrent obstruction. We have found
      that extending the prosthesis 1 cm within the bladder lumen can overcome the
      foregoing complication, although the long-term results have as yet to be
      established.

PMID- 9622918
TI  - [Neurobiology of ejaculation and orgasm disorders].
AB  - OBJECTIVE: To determine the neurologic alterations of patients with ejaculatory
      and orgasmic disorders. METHODS: A study of the neuroandrologic profile was
      performed in eight patients; 6 presented an ejaculation, one premature
      ejaculation and one presented an orgasm. The neuroandrologic profile consisted in
      performing selective electromyography of the bulbocavernosus muscle, recording of
      the S2-S4 evoked potentials, evoked somatosensory potentials of the pudendal
      nerve, electromyography of the smooth cavernous muscle (SPACE), sympathetic skin
      response and cystometry. RESULTS: The sympathetic lesion was more frequent in the
      cases with an ejaculation (four cases; 66%); a pudendal efferent lesion was
      demonstrated in one case (17%) and a suprasacral lesion in one case (16%). A
      pudendal afferent lesion was observed in the two cases with premature ejaculation
      (100%). Both cases with an orgasm had a pudendal afferent lesion (100%) and one
      of them also presented a sympathetic lesion (50%). CONCLUSIONS: An ejaculation
      appears to be caused by sympathetic, motor pudendal or suprasacral lesion. An
      altered perception of genital sensations due to lesion of the afferent pudendal
      pathway appears to be present in premature ejaculation. An orgasm could be
      ascribed to an alteration of the pudendal sensibility or to the absence of
      ejaculation.

PMID- 9622919
TI  - [Priapism. Our experience].
AB  - OBJECTIVE: We report our experience in the diagnosis, medical management and
      surgical treatment of priapism. METHODS/RESULTS: The clinical records of 67
      patients that had been treated for priapism at our hospital from 1978-1994 were
      analyzed for age, race, occupation, marital status, symptoms, treatment,
      complications and time to remission of symptoms following treatment. Sixty-four
      patients were treated surgically and 3 patients were successfully treated
      medically. We performed 52 cavernospongiosal shunts, 14 sapheno-cavernous shunts
      and in 10 patients corpora cavernosa puncture was performed. The complications
      were sepsis, thrombosis, hematoma, phlebitis and urethral fistula. The
      complication rate was low for the cavernospongiosal shunt and corpora cavernosa
      puncture with phenylephrine. CONCLUSIONS: The highest incidence was observed in
      patients aged 15-40 years, with a prevalence in the black race. The principal
      presenting feature was a painful erection without sexual contact. Idiopathic
      priapism was the most prevalent, although the sickle cell anemia was an important
      etiological factor. The surgical technique most commonly used was the
      cavernospongiosal shunt. Intracavernosal injection of phenylephrine was the
      treatment of choice for pharmacological priapism. Seven patients had erectile
      dysfunction.

PMID- 9622920
TI  - [Electric stimulation of sacral roots for the treatment of urinary incontinence
      due to detrusor instability: application of a technique and results in a clinical
      case].
AB  - OBJECTIVE: To describe a case treated with a new technique in our therapeutic
      algorithm for non-neurogenic vesicourethral dysfunction. METHODS/RESULTS: A 47
      year-old female underwent retropubic urethropexy for stress urinary incontinence.
      She remained incontinent due to detrusor instability to a degree that was
      socially unacceptable. After conservative treatment had failed, a percutaneous
      electrode was applied to the sacral nerve root and she received electrical
      stimulation of 4-6 milliamperes, 15 Hz and 200 microseconds duration for 7 days.
      Incontinence remitted for as long as 3 months after the electrode had been
      removed. CONCLUSION: The results achieved with sacral nerve electrical
      stimulation reported in the literature and our results support the use of this
      technique in urological clinical practice.

PMID- 9622921
TI  - [Nephrogenic adenoma in intestinal mucosa. A case in urethro-sigmoid
      anastomosis].
AB  - OBJECTIVE: To describe a case of nephrogenic adenoma occurring in the intestinal
      mucosa of the neobladder urethro-sigmoid anastomosis in a patient who had
      undergone cystectomy for a bladder carcinoma. METHODS/RESULTS: Of 14 cases of
      nephrogenic adenoma in 11 patients, one involved the lamina propria of large
      bowel mucosa. A 67-year-old patient submitted to radical cystoprostatectomy and
      orthotopic bladder substitution using a detubulized sigmoid neobladder due to
      multicentric G3 pTa, pTis urothelial bladder carcinoma had two episodes of
      stricture of the distal anastomosis. After the second episode, endoscopic
      resection of the area was performed. Histological examination of the specimen
      disclosed nephrogenic adenoma of the intestinal mucosa. CONCLUSIONS: Nephrogenic
      metaplasia has been observed in the intestinal mucosa of patients undergoing
      different urological procedures. To our knowledge, our patient is the third case
      involving large bowel mucosa reported in the literature. These three cases
      suggest that nephrogenic adenoma might not be a metaplastic process specific to
      the urothelium.

PMID- 9622922
TI  - [Blue nevus of the prostate. Differential diagnosis of prostatic pigmented
      lesions].
AB  - OBJECTIVE: To describe a case of blue nevus of the prostate and propose a more
      precise terminology in order to avoid the confusion arising from the presence of
      melanin pigment in the prostatic epithelium and/or stroma. METHODS/RESULTS: A 58
      year-old patient with adult polycystic kidney is described. The patient
      demonstrated clinical and radiological findings compatible with benign prostatic
      hyperplasia and had a PSA of 11.4 ng/ml. After three transrectal biopsies showing
      no malignancy, the patient underwent transurethral resection. Pathological
      examination of the specimen disclosed glandular-stromal hyperplasia and extensive
      melanin pigmentation of stroma or blue nevus of the prostate. CONCLUSION: The
      presence of pigment in the prostate is an extraordinary histological finding that
      can be ascribed, in most of the cases, to one of the following conditions: a)
      melanosis or true melanocytosis, in which the melanin pigmentation is produced by
      the prostatic stromal cells, with or without involvement of the surrounding
      epithelium (probably in a secondary passive process); b) pseudomelanosis, in
      which the lipofuscin pigmentation is produced and stored by epithelial cells. In
      both cases the histopathological findings have no clinical significance or
      prognostic implications.

PMID- 9622923
TI  - [Right ectopic hydronephrotic kidney with pelvic lithiasis. Report of a case].
AB  - OBJECTIVE: To report a case of hydronephrotic ectopic kidney with lithiasis and
      pelvic localization, its diagnostic aspects and surgical treatment.
      METHODS/RESULTS: A 39-year-old male consulted at the emergency services for low
      abdominal pain. Physical examination disclosed a hypogastric mass. Patient
      evaluation by ultrasound, intravenous urography and pyelography revealed a right
      hydronephrotic ectopic kidney with lithiasis and pelvic localization. Nephrectomy
      via a right infraumbilical incision was performed. CONCLUSION: Pelvic renal
      ectopy is uncommon, but not rare in our area. This anomaly is associated with a
      higher than normal incidence of hydronephrosis and lithiasis. The diagnostic
      techniques most frequently used to evaluate these patients are ultrasound,
      intravenous urography, cystography and pyelography. When a surgical procedure is
      performed, the anatomical features of this anomalous condition should be
      considered, such as abnormal vascularization, pyelourethral anomalies, kidney
      rotation and absence of perirenal fat tissue.

PMID- 9622924
TI  - [Prostatic malacoplakia: report of a case and review of the literature].
AB  - OBJECTIVE: To describe an additional case of malakoplakia of the prostate. The
      etiopathogenesis, the histological and clinical features of this disease are
      analyzed and the literature briefly reviewed. METHODS/RESULTS: The pathological
      features of malakoplakia of the prostate in an elderly man with severe prostatic
      syndrome and recurrent urinary infections from E. Coli are described. The
      clinical manifestations disappeared following adenomectomy according to the
      Millin technique. CONCLUSION: Diagnosis of malakoplakia of the prostate is based
      on the pathological findings. The importance of the pathologist's role in the
      diagnosis of this condition, which will determine the treatment to follow, is
      therefore underscored.

PMID- 9622925
TI  - [Acute abdomen secondary to pyonephrosis. Perinephritic abscess with fistula to
      peritoneal cavity].
AB  - OBJECTIVE: To describe a case of acute abdomen arising from an underlying
      urological condition. METHODS/RESULTS: Herein we describe a patient with acute
      abdomen arising from a pyonephrotic kidney with fistulization to the peritoneal
      cavity. The clinical manifestations disappeared following nephrectomy by the
      anterior approach and drainage of the intraperitoneal cavity. CONCLUSION:
      Although infrequent, it should be taken into account that peritoneal abscess
      and/or pyonephrosis can cause acute abdomen when they fistulize to the peritoneal
      cavity.

PMID- 9622927
TI  - Renal staghorn calculosis: our experience with the percutaneous treatment with or
      without extracorporeal shock wave lithotripsy.
AB  - OBJECTIVES: In this paper we report our results in the treatment of renal
      staghorn stones by percutaneous lithotripsy (PCNL) with or without extracorporeal
      shock wave lithotripsy (ESWL). METHODS/RESULTS: Over a period of 5 years, 244
      patients with renal calculosis were treated by PCNL in our Department. Seventy
      four of these were cases of renal staghorn calculosis: 44 presented a partial
      staghorn stone and in 30 cases the stone formation completely occupied the
      pyelocalieal cavity. We performed first a PCNL via a rigid nephroscope. Stones
      were crushed using an ultrasonic lithotrite; an electrohydraulic probe was used
      when the calculus was resistant to ultrasound. The patients were submitted to one
      or more percutaneous treatments followed by extracorporeal lithotripsy to
      complete the operation, when required. The patients were divided into two groups
      according to the type of stone: the first group comprised 59 patients with a
      partial or complete simple staghorn stone and the second comprised 15 patients
      with a complete complex staghorn stone. Complete resolution was achieved in 55 of
      the 59 cases (93.2%) in the first group and in 9 of the 15 cases (60%) in the
      second. We had no complications. CONCLUSIONS: Our experience confirms that PCNL
      is the elective treatment for partial and complete staghorn stones and ESWL in
      these types of stones must be utilized only as ancillary treatment for residual
      fragments.

PMID- 9622926
TI  - [Erectile dysfunction caused by neurapraxia of the pudendal nerve after the use
      of a traction table for the treatment of traumatic fractures. Report of a case
      and review of the literature].
AB  - OBJECTIVE: To describe a case of erectile dysfunction as a result of traction on
      the fracture table. METHODS: We report on a 39-year-old man who developed erctile
      dysfunction postoperatively and for several months thereafter, following
      intramedullary nailing with the Grosse-Kept bolt type fixation system. RESULTS:
      The patient spontaneously recovered erectile function six months after
      orthopaedic treatment. CONCLUSION: Erectile dysfunction induced by orthopaedic
      fracture table is a complication that should be taken into account. There are
      many procedures available to reduce the risk of this complication.

PMID- 9622928
TI  - [Eulogy of Etienne Wolff (1904-1996)].

PMID- 9622929
TI  - [Carcinogenesis: from epidemiology to molecular biology].
AB  - Carcinogenesis is a multi-step process and at least three stages can be
      distinguished: initiation, promotion and progression. Initiation is made up of
      events whereby an exogenous or endogenous carcinogen induces alterations in the
      genome of the cell; this results in a lesion that can be inherited and which
      confers upon that cell the potential for neoplastic growth. This is the result of
      activation of cellular proto-oncogenes into transforming oncogenes and/or the
      inactivation of the two alleles of tumor suppressor genes (anti-oncogenes).
      Although it is conceivable that a single event or a single lesion can initiate a
      cell it is probable that in most cases initiation is the consequence of a series
      of events since the different types of proto-oncogenes do not function
      independently of each other. The coordinated activation of more than one oncogene
      is generally required to confer the full potential for neoplastic growth. DNA
      repair and apoptosis play a critical role in carcinogenesis and the effectiveness
      of these mechanisms might be influenced by the dose and the time interval between
      individual events (dose rate). Epidemiological and experimental data show also
      the main role of cell proliferation after initiation. Proliferation influences
      the probability of DNA repair and contributes to further genomic alteration. Cell
      to cell interaction within a tissue participates in the control of cell
      proliferation and cell repair. The evolution of one initiated cell is not
      independent of the surrounding cells and disorganization of a tissue is a factor
      in carcinogenesis. Presently carcinogenesis appears to be a complex phenomenon
      which cannot be a adequately modelled. The linear no-threshold model has been
      used for the purpose of cancer prevention and legal norms, however it should be
      realized that its experimental and theoretical bases are debatable and that much
      recent data do not support them. Its predictions should therefore be considered
      with great caution. All efforts should be made in the future to build new models
      incorporating available epidemiological and fundamental data.

PMID- 9622930
TI  - [Molecular mechanisms of carcinogenesis: the role of systems of DNA repair].
AB  - The initiation step of the carcinogenic process consists in an alteration of
      genes playing a central role in the cellular life. The next steps of promotion
      and progression result from anomalies in the response to growth factors, to
      hormones and/or from the action of tumor promotors leading to cellular
      hyperplasia. This process generally leads to genetic instability of the initiated
      cell which in turn allows selection of malignant and invasive clones. The
      production of DNA damage by physical or chemical agents is dose-dependent. The
      error-free enzymatic repair processes including excision resynthesis of base
      damage or of altered nucleotides allow the restitution of intact DNA. The error
      prone repair systems permit survival in association with transmissible
      alterations (genes and chromosomal mutations). Absence of repair leads to
      cytotoxicity, programmed cell death or disruption of cell cycle control leading
      to a pretumoral state. The major role played by mutations in the initiation of
      carcinogenesis is evidenced by the existence of genetic syndromes associated to
      hypersensitivity to genotoxic agents, defects in DNA repair capacity, anomalies
      in the expression of certain genes (including the tumor suppressor p53 gene,
      etc.) and an elevated predisposition to cancer. Xeroderma pigmentosum which is
      defective in excision-repair, ataxia telangiectasia and Fanconi anemia which are
      associated to anomalies in DNA recombination and the familial type of colon
      cancer HPNCP due to inefficient mismatch repair constitute paradigm for this
      fundamental notion. Alterations in the capacity to rejoin radiation induced DNA
      strand breaks appears to be associated to over-reactions to radiotherapy of
      cancer patients. Also the predisposition to develop secondary thyroid tumors
      following treatment of a primary cancer in childhood seems to involve the same
      defect. The existence in the general population of heterozygotes for such DNA
      repair genes should be taken into account for risk evaluation to therapeutic and
      environmental exposures.

PMID- 9622931
TI  - [Malignant progression and resistance of cancer cells: an inducible survival
      program similar to the SOS system of unicellular organisms induced by
      environmental assaults].
AB  - The hypothesis discussed in this paper states that defence and survival
      strategies of cancer cells against therapeutic approaches are similar in their
      mechanisms and homologous in several genes to the SOS program known in bacteria
      and induced by several assaults. The almost ineluctable malignant progression and
      its acceleration in response to various therapies should then be considered as an
      inducible system inherited from prokaryotes and repressed in multicellular
      organisms through the anti-oncogene system. The later, weakened in case of some
      inherited mutations yields even in sporadic cases to repeated assaults and to the
      decrease with time of internal defences, including antioxidant mechanisms. This
      theory which presents in a new perspective the biological status of cancer in the
      frame of Darwinian evolution and hence the strategies able to control its
      progression, leads itself to some predictions and testable assertions: absence of
      any anti-oncogene homologues in unicellular organisms, built-in weaknesses in
      anti-oncogenes, existence of a common repressor and a common derepressor
      mechanism for several distinct genes involved in cancer and in response to an
      environmental assault, and finally a possible transfer of drug resistance genes
      in malignant cells as it is the case for bacteria submitted to stress conditions.

PMID- 9622932
TI  - [Arsenic and retinoic acid, towards targeted treatments of acute promyelocytic
      leukemia?].
AB  - Acute promyelocytic leukaemia is a key model system in cancer biology. Its
      exquisite sensitivity to retinoic acid constitutes the first example of
      differentiation therapy. The PML/RAR alpha fusion protein generated by the t(15;
      17) translocation is the molecular basis of transformation. PML/RAR alpha induces
      transformation most likely through a dominant negative interference with the
      function of nuclear receptors leading to a differentiation block. The fusion
      protein also delocalizes PML and other nuclear body antigens and this alteration
      of nuclear protein traffic seems to play a role in growth control and apoptosis.
      The clinical response of this disease to retinoids and arsenic trioxide, both of
      which induce the degradation of the fusion protein, constitute the first example
      of a therapy directly targeted to a specific genetic lesion in a human cancer.

PMID- 9622933
TI  - [Hepatitis B virus and hepatocellular carcinoma].
AB  - Hepatitis B is a very important public health problem. Epidemiologic studies have
      shown a relationship between the hepatitis B virus (HBV) chronic carrier state
      and the development of hepatocellular carcinoma. HBV belongs to the Hepadna
      viruses family which includes the woodchuck hepatitis virus (WHV), Woodchucks
      infected with WHV represent a good experimental model to study the viral
      oncogenesis. In 85% of the studied cases, WHV acts by insertional mutagenesis in
      a gene of the myc family, mostly the N-myc2 gene. Expression of the myc genes is
      increased, suggesting the role of the viral enhancer. Study of transgenic mice
      have shown the liver specificity of the WHV action. In man, the liver oncogenesis
      is not explained. Studies are in progress to detect inactivation of tumor
      suppressor genes.

PMID- 9622934
TI  - [Allograft "acceptance" and tolerance: a new concept].
AB  - Discovery of microchimerism in kidney and liver transplantation provided an
      important framework for a better understanding of allograft acceptance, for
      analysis of management problems and for therapeutically oriented transplanted
      research. In these new concept correlations with infectious diseases caused by
      non cytopathic microorganisms, previous enigmas, immunologic reaction, counter
      argument and general immunologic implications are discussed.

PMID- 9622935
TI  - [The unstable shoulder in young subjects. Surgical experience].
AB  - The stability of the scapulo humeral joint depends on three anatomical factors:
      bony: surface and integrity of the glenoid cavity. ligamentous: joint capsula and
      labrum glenoidale. muscular: coordination and condition of the components of the
      rotator cuff that maintains the humeral head in the center of the joint, whatever
      be the position of the arm. Clinically, the most frequent aspect is the anterior
      recurrent dislocation, occurring in young patients.... Other forms are possible:
      posterior, multi directional, associated with a lesion of the rotator cuff in
      elderly patients.... Lately a new aspect was described: the painful and unstable
      shoulder. It is observed in high level sportsmen, who practice throwing sports.
      The only treatment is surgical. Two kinds of techniques are currently used:
      preglenoid transfer of the coracoid process, and different kinds-of
      capsuloplasty. Arthroscopy allows a more precise diagnose, but is not yet a good
      therapeutic procedure. Surgical treatment avoids recurrence in more than 95% of
      cases, but clinical osteoarthritis of the gleno humeral joint is observed in
      about 10% of cases after a long follow up (more than 10 years).

PMID- 9622936
TI  - [Treatment of deep venous thrombosis at home: evolution from ideas to medical
      practice].
AB  - The diagnosis of Deep Venous Thrombosis (DVT) by duplex ultrasound is absolutely
      possible out of specialized centers. Low Molecular Weight Heparins (LMWH) allow
      to obtain a greater efficacy and safety compared to Unfractionated Heparin (UFH).
      The control of LMWH is very reduced. Two studies have just been published on the
      topic of treatment of DVT at home. The group of patients treated at home with
      LMWH is not presenting more complications than the group of patients initially
      treated at the hospital with UFH. Nevertheless, these studies concern a very
      selective population of patients. Our center has been proceeding to a study for 4
      years (1993-1997) in comparing the treatment at home of proximal DVT by LMWH then
      oral anticoagulant, to the initial treatment (10 days) in hospital by also using
      LMWH then oral anticoagulant. The first results show that there is no difference
      between both groups in terms of end-points: death, extension or recurrence of the
      thrombus, pulmonary embolism, bleeding. Therefore, the treatment of some type of
      proximal DVT is possible at home. Nevertheless, it is necessary to be very
      cautions as the population studied so far is a selected one. Etiologies of DVT
      are a constant obsessive fear. DVT or pulmonary embolism represents a real
      general disease which is going to progress along life. The intervention of a
      specialized center is always necessary. It is a work in team which must get the
      upper hand compared to an isolated medical action.

PMID- 9622937
TI  - [Importance of the "Personal Serologic Immunization Card" among travelers].
AB  - The "Personal Immunization Card" is entering more and more in practice, even
      though its existence is not yet acknowledged. One of his advantages is to
      consider the travel medicine counsellor on one hand and the travelling adult on
      the other hand, being able to take a licit decision in account to informative
      data. That means to give the two actors-guarantors of the compliance--the
      responsibility in Public Health, in a domain considered until now in the same way
      as that of vaccinations in Infancy. The obligations and recommendations may not
      be sufficient, it is necessary to be convincing at the adult age. Without a
      doubt, we should get ride of the a priori with the progress in biology. We shall
      update our behaviour.

PMID- 9622938
TI  - [A new inherited metabolic disease: delta1-pyrroline 5-carboxylate synthetase
      deficiency].
AB  - delta 1-pyrroline 5-carboxylate synthetase (P5C synthetase) catalyzes the ATP and
      the NAD(P)H-dependent conversion of L-glutamate to glutamate semialdehyde (GSA)
      which is the metabolic precursor for proline biosynthesis. We described in two
      siblings a paradoxical hyperammonemia with hypoprolinemia and hypoornithinemia
      associated to bilateral cataract, mental retardation, joint laxity and skin
      hyperelasticity. We cloned human P5C synthetase-cDNA by database cloning
      strategy: this cDNA has an open reading frame of 2,385 bases coding for a
      polypeptide of 795 amino acids. Both patients are homozygous for an L396S
      substitution, this amino acid being highly conserved across species. This is the
      first report of a P5C synthetase deficiency in human.

PMID- 9622939
TI  - Anatomical and microstructural factors affecting the electrical activity of the
      heart. Experimental findings and mathematical simulations.
AB  - We developed an experimental preparation in which we record 1500 intramural
      electrograms from the ventricular walls of an isolated dog heart. The heart is
      plunged into an electrolytic tank shaped as a human thorax. The tank carries 1300
      electrodes uniformly distributed in the conducting volume and on its surface. We
      obtain 2800 electric signals which enable us to define the spread of excitation
      and the sequence of repolarization in the heart, and to map the spatial
      distribution of potentials and currents in the heart, in the chest and on the
      body surface during a heart beat. Experimental results and mathematical
      simulations show that excitation, repolarization, the spatial distribution of
      heart potentials and the shape of the electrocardiograms are dominated by a small
      number of anatomical factors, namely: the geometry of the ventricles, the epi
      endocardial rotation of myocardial fibers orientation in the ventricular walls,
      the obliqueness of the fibers relative to the epicardial surface and structure of
      the conduction system.

PMID- 9622941
TI  - [Cloning and characterization of CCRS receptors of chemokines, principal
      receptors of the AIDS virus].
AB  - Chemokine receptors belong to G protein-coupled receptors. The chemokine receptor
      CCR5, that binds M1P-1 alpha, M1P-1 beta and RANTES, was characterized as the
      main coreceptors for M-tropic strains of HIV-1, the most important for the
      transmission of the disease. This receptor is necessary, together with CD4, for
      the entry of the virus in its target cells. A mutant form of the receptor,
      frequent in European populations, confers to homozygotes a strong resistance to
      the virus, and to heterozygotes a relative resistance. We have determined by
      mutagenesis the regions of CCR5 that are important for its interaction with the
      viral envelope and with its natural ligands.

PMID- 9622940
TI  - [Mechanism of the growth and rupture of abdominal aortic aneurysm].
AB  - The relationship between atherosclerosis and abdominal aortic aneurysm
      development is well known. Atherosclerosis cannot explain the whole mechanism.
      Genetic characters of mechanisms leading to abdominal aortic development is
      obvious from this study and others. Our study evidences an increased
      metalloproteases activity in aortic wall proportionally to the size of the
      abdominal aortic aneurysm. A decrease of aortic wall elastin is evidenced
      proportionally to the AAA size. Extractable collagen is significantly increased
      in the aortic wall of patients operated on for aortic rupture.

PMID- 9622942
TI  - [Oncology in relation to aging of the population].
AB  - The constant aging of the population has a profound impact on future health
      policies regarding cancer treatment, because age is the main single determinant
      for developing cancer. A new specialty is now emerging: geriatric oncology. So
      far, the very few data available indicate that elderly patients are often
      misstaged and therefore mistreated, as a result of the lack of appropriate
      instruments for the evaluation of the individual life expentancy. New instruments
      should be developed given the emergency situation created by the explosive
      increase in cancer incidence.

PMID- 9622943
TI  - [Secondary implantation of posterior chamber intraocular lenses in reconstructive
      surgery of the anterior segment and infusion of fluid through the pars plana].
AB  - BACKGROUND: A deep anterior chamber can be perioperative maintained by irrigation
      solution or by viscoelastic material. By longlasting reconstructive procedures
      after penetrating injuries we use an infusion through a pars plana cannula.
      METHODS: Between January 1994 and February 1995 five patients (aged 17-28 years)
      underwent secondary IOL implantation after penetrating eye injury with traumatic
      cataract. The reconstructive procedure was performed 6-11 years after the injury
      and linear cataract extraction. In all eyes corneal scars, iris anterior and
      posterior synechias, vitreous prolaps, and fibrotic posterior capsule remnants
      were present. The preoperative visual acuity ranged from 0.05-1.0. A pars plana
      infusion cannula was positioned 3 mm posterior to the limbus. In one eye with
      glaucoma a trabeculectomy and in two eyes with a greater defect of the posterior
      capsule, a lamellar scleral flap for transscleral suturing of one IOL haptic were
      performed. Then the prolapsed vitreous between cornea and infusion cannula was
      removed using the vitreous cutter. Iris synechiae were blunt or sharp dissected,
      the cortical masses were aspirated, the fibrotic or calcificated lens remnants
      were ectomised and an IOL was implanted into the ciliary sulcus. Two haptics were
      transsclerally fixated. The follow-up period ranged from 4-18 months. RESULTS:
      The surgery duration ranged between 45-90 minutes. No perioperative complications
      were recorded. On the fourth postoperative day bleeding into the anterior chamber
      and vitreous in one patient with transsclerally fixated haptic was observed. The
      blood reabsorbed spontaneously within a week. No complications from the infusion
      cannula could be observed. The postoperative visual acuity is 0.1-1.0.
      CONCLUSIONS: The permanent pars plana infusion maintains a stabile anterior
      chamber depths and intraocular pressure. The deep anterior chamber allows long
      lasting surgical manoevers with less risk of corneal endothelium damage.

PMID- 9622944
TI  - [Personal experience in treatment of glaucoma in children with the Sturge-Weber
      syndrome].
AB  - The authors give an account of their experience with the treatment of secondary
      glaucoma in children with Sturge-Weber's syndrome, followed up on a long-term
      basis (mean follow up period 6 years). Sixteen eyes of 13 children, mean age 10.5
      years during the last check-up were treated: four eyes by medicamentous
      treatment, 12 eyes were operated. A total of 27 operations were performed: 13x
      cyclocryocoagulation, 11x trabeculectomy and including peroperative
      administration of 5-fluorouracil in 3 cases, 2x trabeculotomy and 1x laser
      trabeculoplasty. The criterium of therapeutic success is an intraocular pressure
      < or = 21 torr and a concomitant drop of the tension by at least 30% and absence
      of progression on the papilla or perimeter. In the whole group glaucoma is
      compensated in 11 eyes (68.8%). The most frequent complication was choroid
      ablation after filtration surgery (6x). It developed practically only in older
      children. In two patients bilateral glaucoma was observed despite unilateral
      naevus flammeus. Therefore it is necessary to check always both eyes.

PMID- 9622945
TI  - [Trusopt, a local carboanhydrase inhibitor, in the treatment of glaucoma in
      children (preliminary report)].
AB  - The authors investigated in a group of six children with glaucoma persisting for
      a long time the possibility to use locally applied carbonic anhydrase inhibitor,
      2% dorsolamide hydrochloride in the form of eye drops (TRUSOPT, Merck Co.). In
      the submitted preliminary study they evaluate the effectiveness of the drug in
      glaucoma in children very favourably, previous essential treatment with oral
      acetazolamide could be discontinued in all patients without a deleterious effect.
      The authors did not encounter any undesirable effects of the drug nor
      manifestations of intolerance calling for discontinuation of TRUSOPT treatment.
      This is so far the first communication on TRUSOPT treatment of child glaucoma in
      the available literature.

PMID- 9622946
TI  - [Peroperative administration of 5-fluorouracil during trabeculectomy in
      complicated glaucoma in children].
AB  - The authors evaluate the results of preoperative 5-minute administration of 5
      fluorouracil (5-FU), 50 mg/ml, during trabeculectomy on 11 high risk eyes of
      children with primary and secondary glaucoma. The mean age of the patients was
      7.3 years, the average follow-up period 8.9 months (6-12 months). The intraocular
      pressure (i.o.p) of 11 eyes before surgery varied between 23 and 46 torr, average
      31.5 torr, after treatment it was 13 to 28 torr, average 18.4 torr. The mean drop
      of IOP was 41.6%. In 7 eyes during the last assessment of IOP < 21 torr with a
      drop of more than 30%. The remaining 4 eyes have a was IOP between 25 and 28 torr
      with a reduction of 19-39%. Serious postoperative complications comprised four
      times marked hypotonia with a shallow anterior chamber, twice choroidal ablation
      and once macular oedema associated with transient deterioration of vision. In
      view of the limited therapeutic possibilities of high risk types of glaucoma in
      children postoperative administration of 5-FU is a promising alternative for the
      reduction of IOP.

PMID- 9622947
TI  - [Secondary implantation of anterior chamber intraocular lenses].
AB  - The authors evaluate results of secondary implantation of open-loop, flexible,
      anterior chamber intraocular lenses (IOLs) in the group of 94 patients (94 eyes),
      operated on at the Department of Ophthalmology, University Hospital, Hradec
      Kralove from September 1995 to September 1996. There were 54 women (58.8%) and 40
      men (41.2%). Patient age ranged from 27 to 89 years (mean 70.1 years). Operations
      were performed by 5 surgeons using local anesthesia. Early postoperative
      complications were corneal edema in 2 cases (2.2%), hyphaemia in 2 cases (2.2%)
      and higher intraocular pressure in 1 eye (1.1%). For the control analysis 68
      patients were available. Late complications included transient pressure elevation
      in 11 eyes (16.2%), iris capture syndrome in 1 eye (1.4%) and ulcus corneae in 1
      eye (1.4%). Final best corrected visual acuity 6/9 and better achieved 31
      patients (45.6%). Sixty-one patients (89.9%) were very satisfied or satisfied. On
      the basis of our findings we recommend open-loop, flexible, anterior chamber IOLs
      for secondary implantation, when the use of posterior chamber IOLs is not
      suitable.

PMID- 9622948
TI  - [Residual findings in retrobulbar neuritis during demyelinization].
AB  - Retrobulbar neuritis is a common clinical manifestation of multiple sclerosis. We
      evaluated and compared the results of visual field and fundus examinations,
      visual evoked response and nuclear magnetic resonance of the brain in 37 patients
      with the diagnosis of multiple sclerosis and retrobulbar neuritis. Diffuse,
      peripheral scotomas seemed to be the most often found scotomas on perimetry in
      these patients. In contrary, central scotomas formed just a little part of the
      visual field defects. Each threshold increasing of 0.10 log. units on perimetry
      was followed by increased latencies of 2.5 ms. Each other central scotoma on
      perimetry decreased the visual acuity of the patient for 1.6 lines on the Snellen
      chart. The central visual field examination without periphery in the patients
      with multiple sclerosis and retrobulbar neuritis seems to give false negative
      results.

PMID- 9622949
TI  - [Strabismus surgery in adults].
AB  - The authors operated 24 adult patients with strabismus (20 with concomitant, 4
      with paralytic) aged 18 to 66 years, mean age 30.5 years. They focused attention
      on the possibility to adjust the deviation, to achieve binocular vision and
      postoperative diplopia. Based on their own results and those of other authors
      they found that surgery of strabismus in adults is not only a cosmetic operation.
      The possibilities to adjust the deviation are very favourable, and this applies
      also to achievement of binocular vision. The latter was attained in 66.7% of the
      patients. Postoperative diplopia in patients, incl. those with abnormal retinal
      correspondence, is only a rare complication. The authors recommend that adult
      patients with strabismus demanding operation should not be refused.

PMID- 9622950
TI  - [Visual perceptions in ophthalmic migraine].
AB  - The number of patients with ophthalmic migraine is steadily increasing. The
      symptoms of their attacks are dominated by typical visual aura, followed by major
      or minor headache. The authors present the experience of three physicians who
      observed the symptoms on themselves. The first one has suffered from the disease
      already for fifty years, the second and third one 25 years each. In the
      discussion the authors deal with the differential diagnosis of the disease and
      its possible treatment.

PMID- 9622951
TI  - [Biometry of very short ocular bulbs].
AB  - The authors evaluate the postoperative refractive results of 53 patients with
      extremely short eyes (16.0-20.0 mm) after IOL implantation. As the SRK II formula
      underestimates the A-constant increase for very short eyes, the authors as a
      results of the analysis of the set of patients recommend the A-constant
      recalculation according to formula: A-constant increase = 0.429 x axl x axl -
      18.732 x axl + 206.114 and then the calculation of emmetropizing IOL by SRK
      formula.

PMID- 9622952
TI  - [Functional disorders of the visual field].
AB  - The author describes a group of 12 patients with concentric narrowing of the
      visual field which was not elucidated, with the exception of one patient, even
      after all indicated clinical and paraclinical examinations. He describes
      diagnostic methods providing evidence of the functional character of the impaired
      visual field and presents typical findings of changes of the visual field in
      functional disorders.

PMID- 9622953
TI  - [Borderline blindness, practical blindness and severe visual debility].
AB  - In the presented paper the author explains assessment aspect of social welfare
      departments as regard evaluation of complete of practical blindness with
      reference to generally blinding legal regulations. The author draws attention to
      another interpretation not consistent with these regulations, in chapter 26 of
      the Compendium of Ophthalmology (Grada 1997) and recommends ophthalmologists to
      use a procedure which will prevent imminent difficulties which could arise as a
      result of the interpretation in chapter 26 of the Compendium.

PMID- 9622954
TI  - [The Pelli-Robson contrast sensitivity test].
AB  - The author gives the first information on the practical experiences with the new
      examining method finding out the sensitiveness to contrast according to Pelli
      Robson at ophthalmology department in Trnava. This examining method allows to
      gain more complex and quality information about sight quality. It makes possible
      to reify the lower sight quality in cases of normal values of central visual
      acuity examined by a classic method, e.g. by means of Snellen optotypes. The
      examination is more and more used at some chosen professions, those requiring
      work under difficult light conditions, such as drivers, pilots, engine-drivers
      etc. The examination can quicker help to discover endangered eye diseases.

PMID- 9622955
TI  - [Relation of anisometropia and the extent of amblyopia].
AB  - The author deals with the problem of impaired binocular vision in children and
      the problem of the relationship of amblyopia and different refractions of the two
      eyes. Controversial views in the literature ar corrected by the author's
      evaluation of her own material, i.e. refraction of 939 children aged 3-6 years
      subjected to sciascopy during cyclopegia. The author concludes that in
      isometropia and low grade anisometropia various grades of amblyopia are found in
      monocular strabism. When the refractory difference is higher than 1 dioptre there
      is already a direct relationship between the level of anisometropia and the depth
      of amblyopia which is particularly marked when the difference is higher than 2
      diopters. In amblyopia without strabism the relationship between amblyopia and
      anisometropia is unequivocal.

PMID- 9622956
TI  - [Refractive errors, their development, characteristics and correction].

PMID- 9622957
TI  - [Results of surgical treatment of pterygium].

PMID- 9622958
TI  - [Voluntary sterilization in France and in developed countries].

PMID- 9622959
TI  - [The fetus and consent: how to explain?].

PMID- 9622960
TI  - [Counseling in therapeutic abortions].

PMID- 9622961
TI  - [Treatments for menopause].

PMID- 9622962
TI  - [What about colposcopy?].

PMID- 9622963
TI  - [Analysis of natural family planning failures. In 7007 cycles of use].
AB  - MATERIALS AND METHODS: The analysis concerned 626 users using NFP in order to
      avoid a conception during a total of 6740 cycles. Participation in the study did
      not interfere with their plan of conception, and they were invited to behave, as
      far as possible, as though they ignored the study. Of these 626 couples, 530 were
      french, 61 belgian and 35 swiss. On the whole, 39.3% used birth control to limit
      births and 60.7% to space them. RESULTS: The observed pregnancy rates are 1.13,
      6.47 and 17.58 for one year in actuarial method respectively for method, method +
      user and total pregnancy rate. The pregnancy rate was higher for women before 35
      years (RR: 3.8; 95 p100 confidence interval: 1.4-10.3), during the six months
      after delivery (RR: 2.5; 1.0-4.6) and, of course, for couples with inprotected
      sexual intercourse in fertile phase (RR: 4.8; 2.1-11.2). DISCUSSION: NFP can be
      placed among methods of great theorical effectiveness. But pregnancies as a
      result of intercourses during the fertile phase despite its identification are
      frequent: couples have to be informed.

PMID- 9622964
TI  - [Contraception by subcutaneous Norplant implants. 300 cases].
AB  - It is a prospective study for the evaluation of the efficiency and the
      acceptability of Norplant contraceptive subdermal implants within the Senegalese
      female population. Three hundred women were selected on the basis of precise
      criteria between December 1986 and July 1991. Every patient included in the study
      signed a form of voluntary consent with the agreement of the consort, and was
      bound to come to control examinations until the removal of the implants. The
      insertion was made under local anaesthesia between the 1st and the 7th day of the
      cycle, or starting from the 6th week of post-partum in the other cases. The
      average age of patients was 32, and the average parity four children. 50 percent
      of women did not want any other children. The average insertion time is 4.8
      minutes. The analysis of side-effects on 248 regularly followed women mostly
      reveals menstrual troubles like amenorrhea, spottings, menorrhagia. The fitful
      local prurigo was noted in 35 cases, and accidental pregnancy in 4 cases. The
      removal of implants within the first six months was made on 11 women (4.4%). As
      such, the Norplant implants constitutes a highly efficient method, well tolerated
      by Senegalese women.

PMID- 9622965
TI  - [Intrauterine insemination with the husband's sperm: conclusions of five years
      experience].
AB  - We analyzed retrospectively 936 intrauterine insemination (IUI) cycles with
      husband's sperm (384 couples). Superovulation and induction monitoring occurred
      in the majority of cases; IUI was timed 36-40 h after ovulatory hCG. The overall
      pregnancy rate per cycle (PR/C) was 11.4% (107/936). Data analysis demonstrated
      that PR/C decreased with infertility duration, woman's age (especially after 38
      years old) and number of attempts (significantly after the 4 th cycle).
      Superovulation (in particular by antiestrogens) and induction monitoring seemed
      to provide an increase in cycle pregnancy rate. Highest PR/C were observed in
      dysovulation and male infertility groups. In cases of sperm defects, our data
      showed that 2 parameters had a significant influence on pregnancy outcome: the
      number of motile progressive inseminated spermatozoa (> 300,000) and the
      spermatozoa survival rate after 24 h (> 50%). As a conclusion, intrauterine
      insemination can be proposed as a satisfying treatment of infertility, if precise
      protocol is followed and its indications well-defined.

PMID- 9622966
TI  - ["Step protocols"].
AB  - Within the last decade, induction of ovulation with gonadotrophins, specially for
      patients with polycystic ovary syndrome, has been extensively revisited. On the
      basis of physiological concepts as the FSH threshold, the FSH window and the
      hypersensitivity to FSH of selected dominant follicle, news protocols have been
      described: step-up protocol, step-down, sequential protocol. In this article,
      their efficacy and safety are discussed. It is presumed that these new protocols
      would open a new way in the management of ovulation induction.

PMID- 9622967
TI  - [Evolution and infection control security in endoscopic surgical
      instrumentation].
AB  - The evolution of the endoscopic equipment in gynecologic surgery for the last
      years makes this procedure easier, more reliable and performant, with decreased
      morbidity. The instruments are more and more specific. The place and the interest
      for single use instruments will probably be modified. On the other side,
      nosocomial infections are spreading and the sterilisation procedures of the
      endoscopic surgical instruments, often more flimsy, are more drastic. It modify
      the working plan and the functioning costs of the operative rooms but it's now a
      legal point to respect this evolution.

PMID- 9622968
TI  - [Medical history questionnaire of psycho-environmental factors].

PMID- 9622969
TI  - [Psychosexual disorders. Anorgasmy and dysorgasmy].

PMID- 9622970
TI  - [Treatment of common sexual dysfunctions].

PMID- 9622971
TI  - [Classification of antibiotics according to resistance induction. Interview by
      Dr. rer. nat. Anita Schweiger].

PMID- 9622972
TI  - [Diagnosis and therapy of malignant lymphedema].
AB  - In addition to the typical clinical symptoms, the diagnosis "malignant
      lymphedema" also requires the confirmation of a tumor or a metastasis obstructing
      lymph flow. With the standard physical treatment of edema described by Asdonk
      successful clinical management of malignant lymphedema is also possible. The sole
      contraindication of manual lymph drainage is, we believe, locoregional tumor
      recurrence, which can be completely eliminated by the immediate initiation of
      radical tumor treatment. The tumor recurrence is the result not of falsely
      indicated manual lymph drainage, but of inadequate primary treatment that leaves
      behind residual tumor tissue, the early detection of which still remains an
      unresolved problem. Manual lymph drainage is indispensable for improving the
      quality of life of tumor patients with lymphedema.

PMID- 9622973
TI  - [Erysipelas and lymphedema].
AB  - The most common complication of lymphedema is erysipelas (Saint Anthony's fire).
      The protein-rich lymph is such an excellent medium for the growth of bacteria
      that the risk of erysipelas developing is as high in the most severe forms of
      lymphedema as 50% compared with only 1/1000 in the general population. Treatment
      requires the use of antibiotics. Of importance for prophylaxis is the rigorous
      disinfection of minor injuries that provide a portal for bacteria, usually
      streptococci, and the physical edema therapy described by Asdonk comprising
      manual lymph drainage and compression.

PMID- 9622974
TI  - [Consulting the expert. Sudden pain and swelling].

PMID- 9622975
TI  - [Diagnostic imaging in rheumatology. 2: Indications for imaging methods--staged
      diagnostic plan in rheumatoid arthritis and ankylosing spondylitis].

PMID- 9622976
TI  - [Retard morphine for oral pain therapy. Once daily administration as basic opioid
      -experiences with 2,840 patients].

PMID- 9622977
TI  - [Xeroderma pigmentosum].

PMID- 9622978
TI  - [Allergic rhinitis: allergen elimination would be the ideal solution].

PMID- 9622979
TI  - [Is insurance responsibility with rationing possible?].

PMID- 9622980
TI  - Management of acute ischaemic coronary syndromes beyond aspirin therapy: role of
      glycoprotein IIb/IIIa antagonists.

PMID- 9622981
TI  - Brain natriuretic peptides.

PMID- 9622982
TI  - Safety of thrombolytic therapy following acute myocardial infarction in patients
      above 65 years.
AB  - The safety of thrombolytic therapy for acute myocardial infarction in the elderly
      population has not been clearly established. In a retrospective study we
      evaluated the efficacy and complications of thrombolytic therapy in the elderly
      as compared to younger patients. Consecutive 588 patients who received
      thrombolytic therapy were studied. Clinical data in 136 patients aged above 65
      years were compared with 85 patients below 40 years. Cigarette smoking was a
      common risk factor in the young (46 vs 13; p < 0.0001). Coexistent systemic
      diseases and conduction system disturbances (28 vs 9; p < 0.05) were common in
      the older patients, but the incidence of bleeding complications to thrombolytic
      therapy (6 vs 1; p = NS) was not found to be higher. Ninety percent of the
      elderly who had cardiogenic shock died. There was no significant difference
      between the two groups in reinfarction rate (12 vs 15; p = NS) and post-infarct
      angina (20 vs 20; p = NS). Coronary angiography revealed a higher incidence of
      multivessel disease in the elderly. To conclude, thrombolytic therapy is safe and
      effective even in older individuals.

PMID- 9622983
TI  - Fast track thrombolysis in acute myocardial infarction: a quality improvement
      project.
AB  - Thrombolytic therapy for acute myocardial infarction has been proved to be most
      effective if given very early in the course of evolving infarction. This study
      was undertaken to optimise such treatment by overcoming the in-hospital delay in
      the existing set-up of an industrial hospital. A quality improvement project was
      undertaken to analyse the existing system of thrombolysing 46 consecutive
      patients of acute myocardial infarction treated in six months. By following the
      breakthrough sequence and proceeding in steps, the causes for delay in door to
      needle time were identified and rectified over two months. Impact of such
      measures in 32 patients of acute myocardial infarction thrombolysed consecutively
      in the next five months was studied. Door to needle time in the baseline group (n
      = 46) was in the range of 15-145 minutes and the average was 48.9 minutes. Only
      32.6 percent of the patients in this group were thrombolysed within 30 minutes of
      arrival in the hospital. After the corrective measures were implemented in a
      study group of 32 patients, 27 with clear indication on admission were
      thrombolysed on the fast track i.e. with minimum delay. Five patients with
      doubtful need were put on the slow track and subsequently thrombolysed. Patients
      with no indication or a contra-indication for thrombolysis were excluded from
      this study. In the fast group, door to needle time reduced to an average of 22.56
      minutes with a range of 7 to 67 minutes and 75 percent of the thrombolysed
      patients received the infusion within 30 minutes of arrival in the hospital.
      Differences in door to needle time between the two groups were statistically
      significant. Streamlining the hospital systems and procedures can help reduce the
      door to needle time in thrombolysing patients of acute myocardial infarction.
      This could be achieved within the existing resources by applying the principles
      of total quality improvement.

PMID- 9622984
TI  - Acute haemodynamic effects of nicorandil in patients with chronic severe
      regurgitant valvular lesions.
AB  - The haemodynamic effects of nicorandil, a new balanced vasodilator exhibiting
      nitrate-like as well as potassium-channel opening activity in patients with
      chronic severe valvular lesions have not been reported. We studied the acute
      effect of nicorandil on haemodynamics in 12 stable patients (6 males, 6 females;
      mean age 23.5 +/- 4.6 years) with chronic severe valvular regurgitation (8
      mitral, 4 aortic). All patients were studied in resting, supine and fasting
      states. All cardioactive drugs were withdrawn five days prior to the study. Intra
      arterial line was placed and thermodilution catheter was positioned in the
      pulmonary artery. Haemodynamic parameters recorded at baseline and at 30, 60, 90
      and 120 minutes following a single oral dose of 20 mg nicorandil revealed no
      significant change in the heart rate while systemic pressures showed a small
      decline (p < 0.05). There was significant reduction in systolic, diastolic and
      mean pulmonary artery pressures (p < 0.001). The mean cardiac index increased
      from 3.16 L/min/m2 at baseline to 3.77 L/min/m2 at 60 minutes. Both the pulmonary
      and systemic vascular resistance indices reduced significantly, the peak fall
      being 18 percent and 29 percent, respectively. Maximal changes were observed at
      60 to 90 minutes following administration of nicorandil. No adverse effect of
      nicorandil occurred during the study. We conclude that nicorandil has a
      favourable acute haemodynamic effect in patients with chronic severe valve
      regurgitation. Its long-term use in valvular lesions should be explored further.

PMID- 9622985
TI  - Acute effect of balloon mitral valvotomy on serial electrocardiographic changes
      and their haemodynamic correlation.
AB  - The effect of acute haemodynamic changes that occur following balloon mitral
      valvotomy on the electrocardiogram were studied in 25 patients with isolated
      rheumatic mitral stenosis. Statistically significant changes were observed in the
      characteristics of P-wave and QRS axis. Patients who showed changes in P-wave had
      significantly greater fall in left atrial mean pressure (p < 0.025), lesser
      residual transmitral gradient (p < 0.025) and greater percentage change in mitral
      valve area (p < 0.01) following balloon mitral valvotomy. Good correlation was
      seen between the decrease in right axis deviation of QRS axis and fall in mean
      pulmonary artery pressure (r = +0.56, p < 0.001) and pulmonary vascular
      resistance (r = +0.48, p < 0.05). Transient arrhythmias were seen in six
      patients. All these changes occurred within 72 hours, and in the majority of
      patients within 24 hours. These results demonstrate that the acute haemodynamic
      changes following balloon mitral valvotomy produce corresponding changes on
      electrocardiogram and these changes indicate a significantly greater degree of
      haemodynamic benefit from the procedure than when these changes are not seen.

PMID- 9622986
TI  - Elective stenting of unprotected left main coronary artery ostial stenoses: short
      and mid-term results.
AB  - Elective stenting as a primary strategy for non-surgical revascularisation was
      performed in five patients with symptomatic unprotected left main coronary artery
      ostial stenoses. Their ages ranged from 24 to 57 years (mean: 44.6 +/- 14.4
      years). Left ventricular ejection fraction ranged from 35 to 55 percent. All
      patients underwent successful stenting for left main ostial stenoses using a
      disarticulated 7 mm Palmaz-Schatz stent. Luminal diameter stenosis reduced from
      74 +/- 10.8 to 10 +/- 7.2 percent after the procedure. One patient developed
      recurrence of angina on the 7th day due to marked recoil of the left main
      coronary artery with possible thrombosis, requiring immediate coronary artery
      bypass graft surgery without any sequelae. Remaining four patients were
      asymptomatic over a mean follow-up of 54 +/- 36 weeks (range: 25-96) and none
      developed angiographic restenosis at six months. Our preliminary observations
      therefore suggest that primary stenting is a feasible alternative to bypass graft
      surgery in patients with unprotected left main coronary artery ostial stenoses.

PMID- 9622987
TI  - Balloon dilatation of simple aortic coarctation in neonates and infants.
AB  - Twenty-one infants with isolated native coarctation of aorta (mean age 4.73 +/-
      2.85 months, range 15 days-12 months) underwent balloon dilatation in the last
      seven years at our institute. Seven of them were less than three months and 14
      were older than three months. The procedure was successful in relieving the
      coarctation (gradient < 20 mm Hg) in five of seven (71%) infants up to three
      months and 12 of 14 (86%) above three months. Peak systolic gradients decreased
      from 70.8 +/- 20.1 to 14.5 +/- 11 mm Hg in the younger infants and from 47.7 +/-
      11.7 to 11.4 +/- 9.9 mm Hg in infants above three months. Post-dilatation
      angiogram showed the coarctation segment to be equal to the isthmus in both the
      groups, 0.96 +/- 0.14 and 0.96 +/- 0.12 respectively. One three months old infant
      died immediately after a successful dilatation possibly due to coronary embolism,
      and another neonate died a few days later of unrelated pre-existing septicemia.
      Left ventricular function improved in all the infants with depressed preprocedure
      ejection fraction. Restenosis defined as peak instantaneous echo-Doppler gradient
      above 20 mm Hg with a significant narrowing on two-dimensional echocardiography
      occurred in all the five infants up to three months over a period of 1 to 12
      months. Follow-up information over a period of 4 to 24 months was available in 11
      of 14 older infants of which three had restenosis. Gradients progressively
      increased in all the four infants (2 of either group) with an initial partially
      successful result. A small isthmus relative to the descending thoracic aorta at
      diaphragm is an important predictor of restenosis/inadequate result. This
      discrepancy was seen much more in smaller infants, post-dilatation coarctation
      index being 0.68 +/- 0.11 vs 0.81 +/- 0.16 (p = 0.07). Four of the infants
      underwent a repeat successful dilatation. Balloon dilatation is safe and
      effective in infants above three months of age. In infants up to three months the
      procedure is feasible and leads to improvement in left ventricular function, but
      restenosis occurs rapidly in all of them.

PMID- 9622988
TI  - Scope and efficacy of complex radiofrequency ablation.
AB  - Radiofrequency ablation is an effective treatment for various tachycardias. In
      some patients undergoing radiofrequency ablation, there are additional
      complexities. Of 254 consecutive patients (161 males, 93 females, aged 38 +/- 15
      years) who underwent radiofrequency ablation, two groups were identified.
      Patients with structural heart disease, multiple accessory pathways, multifocal
      idiopathic ventricular tachycardia, parahisian accessory pathways, and multiple
      mechanisms of tachycardia were considered as complex radiofrequency ablation
      (Group I) and the remaining as non-complex radiofrequency ablation (Group II).
      There were 23 patients in Group I. The overall success rate was not different in
      the two groups: 20/23 (87%) vs 208/231 (90%) in groups I and II, respectively.
      The procedure and fluoroscopy time (212 +/- 91 min vs 136 +/- 45 min; p = 0.0001;
      and 55 +/- 31 min vs 31 +/- 21 min; p = 0.001, respectively) were significantly
      longer in Group I. There was a higher recurrence rate in Group I (6/20, 30% vs
      20/208, 9.6%; p = 0.02); repeat radiofrequency ablation was successfully
      performed in four patients with recurrence in Group I. Complications were rare in
      both the groups. There was no mortality. Thus radiofrequency ablation in complex
      situations was effective, though more demanding than non-complex radiofrequency
      ablation and associated with higher recurrence.

PMID- 9622989
TI  - Peripartum fungal endocarditis of native mitral valve.

PMID- 9622990
TI  - Pacemaker implant site infection caused by atypical mycobacteria.

PMID- 9622991
TI  - Rotablation-induced coronary perforation during management of in-stent
      restenosis.

PMID- 9622992
TI  - Isolated innominate artery in association with patent ductus arteriosus and left
      pulmonary arterial ostial stenosis.

PMID- 9622993
TI  - Unruptured sinus of Valsalva aneurysm dissecting into ventricular septum:
      diagnosis by echocardiography.

PMID- 9622994
TI  - Double orifice mitral valve with gross regurgitation in both orifices.

PMID- 9622995
TI  - Extracardiac Fontan operation on beating heart: a case report.

PMID- 9622996
TI  - Management of atrial fibrillation: rate vs rhythm control.

PMID- 9622997
TI  - Yoga and coronary artery disease.

PMID- 9622998
TI  - Is administration of nitrates an offence in suspected cases of angina pectoris?

PMID- 9622999
TI  - Performance discrepancies between the Children's Category Test (CCT) and the
      California Verbal Learning Test-Children's (CVLT-C) Version in the
      standardization sample.
AB  - Standardization data for the Children's Category Test (CCT) and California Verbal
      Learning Test-Children's Version (CVLT-C) were used to evaluate covariances and
      statistically significant discrepancies between the T scores of those
      instruments, as well as the base rate of specific discrepancies. The results
      indicate that the CCT and CVLT-C share only a limited amount of common variance
      and that statistically significant discrepancies between the respective T scores
      are actually quite common. It is suggested that evaluation of the potential
      clinical significance of a discrepancy between the obtained results of these two
      instruments in individual cases should include consideration of the presented
      base rates.

PMID- 9623000
TI  - The effects of focal and diffuse brain damage on strategy application: evidence
      from focal lesions, traumatic brain injury and normal aging.
AB  - A new test of strategy application was designed to be relatively free of the
      constraints that limit the standard neuropsychological assessment of supervisory
      abilities. The validity of the test was assessed in 3 samples of participants
      with varying degrees of supervisory deficits and frontal systems dysfunction:
      focal frontal lesions, traumatic brain injury (TBI), and normal aging.
      Inefficient strategy application varied systematically across the 3 groups and
      was not due to extraneous factors such as forgetting the test instructions.
      Previous case studies have emphasized strategy application deficits in the face
      of normal neuropsychological test performance. In this study, it was shown that
      strategically impaired participants from a consecutive series can include those
      both with and without deficient neuropsychological test performance. When
      neuropsychological impairment was present, it was greatest on executive
      functioning tasks. Among participants with nonstrategic performance, there was
      evidence for a dissociation of knowledge from action. This finding was not
      specific to focal frontal lesions. A number of supervisory processes contributing
      to strategy application were identified. Exploratory analyses indicated
      differential effects of lesion location on these processes, especially inferior
      medial frontal and right hemisphere lesions. Overall, the results supported the
      use of unstructured tasks in the assessment of supervisory abilities.

PMID- 9623001
TI  - The effects of focal anterior and posterior brain lesions on verbal fluency.
AB  - Seventy-four patients with focal brain lesions were compared to a neurologically
      normal control group on tasks of letter-based and category-based list generation.
      When patients were divided only by right frontal, left frontal, or nonfrontal
      lesion sites, the pattern of fluency impairments confirmed prior claims. When
      more precise lesion sites within the frontal lobes were compared between groups
      classified based on their fluency performance, much more specific brain-behavior
      relations were uncovered. Damage to the right dorsolateral cortical or connecting
      striatal regions, the right posterior area, or the medial inferior frontal lobe
      of either hemisphere did not significantly affect letter-based fluency
      performance. Superior medial frontal damage, right or left, resulted in moderate
      impairment. Patients with left dorsolateral and/or striatal lesions were most
      impaired. Left parietal damage led to performance relatively equivalent to the
      superior medial and left dorsolateral groups. The same lesion sites produced
      impairments in category based fluency, but so did lesions of right dorsolateral
      and inferior medial regions. Task analysis and correlations with other measures
      revealed that different cognitive processes related to different brain regions
      underlie performance on verbal fluency tests.

PMID- 9623003
TI  - Age of disease onset influences cognition in Parkinson's disease.
AB  - It is controversial whether age of disease onset is related to cognitive decline
      in Parkinson's disease (PD). We administered 7 cognitive measures assessing
      visuospatial skills, memory, and executive functions to 222 patients with
      idiopathic PD and 108 normal control participants. Regression analyses
      demonstrated that older age of disease onset consistently predicted cognitive
      decline above and beyond normative aging and duration of illness. These findings
      suggest that older age of disease onset is a critical determinant of cognitive
      deterioration in PD.

PMID- 9623002
TI  - Prospective comparative study of the evolution of probable Alzheimer's disease
      and Parkinson's disease dementia.
AB  - No previous comparison of test performance in probable Alzheimer's disease (pAD)
      and Parkinson's disease (PD) dementia has provided information about potential
      differences in the dementing process. This study compared the evolution of
      cognitive changes associated with these dementias. Generalized estimating
      equations (GEE) applied to regression analyses with repeated measures were used
      to evaluate cognitive changes over 1 to 3 years prior to the point when dementia
      was diagnosed in 40 matched pairs of patients with incident pAD and PD dementia.
      Both groups' performance declined on the Short Blessed, Selective Reminding Test
      (SRT; total recall, long-term retrieval, and delayed recall), Boston Naming Test,
      Category Fluency, and Similarities. The decline on naming and SRT delayed recall
      was more rapid in the PD dementia group, suggesting that these performance
      deficits emerge earlier in the development of pAD. The PD dementia group
      performed worse on Category Fluency throughout the follow-up period, suggesting
      either that dementia is overlaid on this preexisting performance deficit or that
      this type of executive deficit is an early manifestation of dementia in PD. The
      pAD group performed more poorly throughout the follow-up period on SRT delayed
      recognition, consistent with a pAD-specific encoding deficit. We conclude that
      while pAD and PD dementia are similar in many respects, differences in their
      evolution support previous observation of unique features in the 2 dementias and
      suggest different underlying pathologies.

PMID- 9623004
TI  - The effect of African-American acculturation on neuropsychological test
      performance in normal and HIV-positive individuals. The HIV Neurobehavioral
      Research Center (HNRC) Group.
AB  - Two studies were conducted to examine the relationship of acculturation to
      neuropsychological test performance among (1) medically healthy, neurologically
      normal African Americans (N = 170); and (2) HIV positive (HIV+) subgroups of
      African Americans and Whites (Ns = 20) matched on age, education, sex, and HIV
      disease stage. Acculturation was measured through self report for all
      participants, and linguistic behavior (Black English use) was assessed in a
      subset of medically healthy individuals (N = 25). After controlling for the
      effects of age, education, and sex, medically healthy African Americans who
      reported less acculturation obtained lower scores on the WAIS-R Information
      subtest and the Boston Naming Test than did more acculturated individuals. Black
      English use was associated with poor performance on Trails B and the WAIS-R
      Information subtest. HIV+ African Americans scored significantly lower than their
      HIV+ White counterparts on the Category Test, Trails B, WAIS-R Block Design and
      Vocabulary subtests, and the learning components of the Story and Figure Memory
      Tests. However, after accounting for acculturation, ethnic group differences on
      all measures but Story Learning became nonsignificant. These results suggest that
      there are cultural differences within ethnic groups that relate to
      neuropsychological test performance, and that accounting for acculturation may
      improve the diagnostic accuracy of certain neuropsychological tests.

PMID- 9623005
TI  - Traumatic hematomas of the posterior cranial fossa.
AB  - The objective of this study was to find out the result of treatment and the
      factors which can predict the outcome of traumatic hematomas of the posterior
      cranial fossa. Twenty two patients with traumatic hematomas of the posterior
      cranial fossa from 1,500 patients with traumatic intracranial hematomas were
      analyzed. There were fourteen male and eight female patients. The most common
      etiology was a motor vehicle accident. About 90 per cent of the patients had a
      direct injury to the occipital region. Ninety per cent of the patients had an
      occipital skull fracture or diastatic fracture of the lambdoid suture. The
      overall mortality rate was about 38 per cent. Patients having pure epidural
      hematoma had zero mortality. By contrast, patients suffering epidural hematoma
      with associated intracranial hematoma had 20 per cent mortality. Intracerebellar
      hematoma led to 60 per cent mortality. Glasgow Coma Scale (GCS) before operation
      was used to predict the patients' outcome. Ninety per cent of the patients who
      had a GCS between 13 and 15 had a good recovery. By contrast, only 30 per cent of
      the patients who had a GCS below 9 had a good recovery. Statistical analysis
      showed that the GCS value of below 9 predicted the poor outcome for the patients.

PMID- 9623006
TI  - Urinary incontinence in Thai elderly living in Klong Toey slum.
AB  - Seven hundred and three non-institutionalized Thai elderly living in Klong Toey
      slum were interviewed at home about their urinary symptoms and 114 cases of
      established urinary incontinence were identified. The prevalence of established
      urinary incontinence was 16.2 per cent. The commonest type is pure urge
      incontinence (58.8%). 24.4 per cent of male subjects with established
      incontinence had symptoms of outlet obstruction. 54.4 per cent of subjects were
      classified as severely incontinent. More than 50 per cent had at least one
      psychological impact and 7.9 per cent reported that their social lives were
      severely affected. Only 8.8 per cent had sought medical help before and only 30
      per cent were willing to attend a specialist at a university hospital. The
      attitude of the elderly, the carers and medical doctors toward urinary
      incontinence has to be corrected. Urinary incontinence should be a public health
      issue in Thailand and there may be considerable scope for the provision of
      incontinence service at the primary health care level.

PMID- 9623007
TI  - Risk factors of diabetic retinopathy in non-insulin dependent diabetes mellitus.
AB  - A prospective study was carried out in non-insulin dependent diabetic patients
      who attended the Diabetic Clinic of Chonburi Hospital from 1991 to 1992.
      Laboratory investigations, physical examination of vascular disorders, and fundus
      examination were done. 198 cases with complete data were analysed. Of these
      patients, sixty three cases had retinopathy, 54 cases had background diabetic
      retinopathy and 9 cases had proliferative diabetic retinopathy. The average
      duration of diabetes with diabetic retinopathy was 7.4 +/- 5.0 years compared to
      4.8 +/- 3.6 years of diabetes without diabetic retinopathy. The mean age of
      patients with and without diabetic retinopathy was significantly different. The
      highest rate of diabetic retinopathy was in the range of 51-60 age group. Fasting
      blood levels of glucose, glycosylated hemoglobin, cholesterol, triglyceride, high
      density lipoprotein, blood pressure (both systolic and diastolic), alcohol
      drinking, and cigarette smoking were not different between diabetic retinopathy
      and non-detected diabetic retinopathy patients but inadequate exercise might be
      related to retinopathy.

PMID- 9623008
TI  - Prevalence of asthma, rhinitis and eczema in children from the Bangkok area using
      the ISAAC (International Study for Asthma and Allergy in Children)
      questionnaires.
AB  - Within the past three decades, there has been a rising trend for prevalences of
      asthma and allergic diseases worldwide, particularly from developed and
      industrializing countries. In Thailand, limited studies on epidemiology of atopic
      diseases have indicated relatively low prevalences of these conditions among the
      Thais. Recently, a standardized phase I questionnaire of the International Study
      of Asthma and Allergies in Childhood (ISAAC) has been developed to study and to
      compare geographical and temporal trend for prevalences of asthma, allergic
      rhinitis and eczema in children. The objectives of phase I ISAAC study in
      Thailand are to study prevalence of the three most common allergic diseases i.e.
      asthma, allergic rhinitis and eczema among Thai children of the two age groups
      (i.e., 6-7 and 13-14 years) living in the Bangkok metropolitan area and to
      collect basic epidemiologic data of these diseases among these children. The Thai
      translated version of phase I ISAAC questionnaires was administered to Thai
      children of the two age groups as above. Questionnaires were answered by parents
      of younger children, whereas, they were self-administered by 13-14 years old
      children. In addition, the validated international video questionnaires were used
      with older children. Fourteen primary schools and 13 secondary schools were
      randomly selected to cover the entire Bangkok metropolitan area. A total of 7341
      questionnaires were eligible for the analysis (3628 from the younger age group
      and 3713 from the older age group). Data were entered and analysed by the Epi
      Info program. The cumulative and 12 month period prevalences of the three
      conditions for all children were as follows; wheezing, 18.3 per cent, 12.7 per
      cent; rhinitis, 44.2 per cent, 38.7 per cent; and eczema, 15.4 per cent, 14.0 per
      cent, respectively. The period prevalence of wheezing for older children (13.6%)
      was higher than for younger children (11.7%). Prevalences of severe wheeze and
      exercise wheeze were more common among older children (4.0% and 15.7%). Both age
      groups reported high percentages for night cough (23.6% and 28.6%). A
      significantly large number of children from both groups reported symptoms of
      rhinitis with the majority indicating that symptoms were severe enough to limit
      their daily activities. Nevertheless, when confined only to those with eye
      symptoms, the prevalence decreased to 13.1 per cent. Eczema, in contrast to the
      other two conditions, occurred more frequently among younger children than among
      older children (period prevalence of 16% vs 9.1%). The rash was of a relatively
      mild nature since 77 per cent of children reporting symptoms indicated that the
      rash had cleared within the past 12 months. Allergic conditions are very common
      among children residing in Bangkok. Compared to the last survey in 1990, the
      period prevalence of wheezing has increased 4 fold, allergic rhinitis has
      increased nearly 3 fold whereas, eczema has remained stable. A large number of
      children in Bangkok are suffering from rhinitis symptoms. Results of this phase I
      ISAAC study indicate that allergic diseases are perhaps the most common childhood
      diseases in Thailand and could lead to a substantial economical loss for the
      country. There is an urgent need for an in-depth study to define epidemiological
      factors responsible for this increase.

PMID- 9623009
TI  - A randomized clinical trial comparing the efficacy of ranitidine and famotidine
      on intragastric acidity in critically ill pediatric patients.
AB  - We examined the efficacy of intravenous ranitidine and famotidine on raising
      intragastric pH in each of 10 critically ill pediatric patients. The severity of
      illness was assessed by using the modified zinner index score. The study had 3
      phases and each phase took 24 hours. Intragastric pH was measured by continuous
      pH monitoring digitrapper for 72 hours. In phase 1 and 3, the patients did not
      receive any H2 blockers. In phase 2, they were randomized to receive intravenous
      ranitidine or famotidine. The majority of cases had intragastric pH < 4 in day 1
      (base line). Ranitidine and famotidine increased total time of intragastric pH >
      or = 4 from the base line during day 2, 38.2 +/- 16.9 per cent and 60.3 +/- 24.8
      per cent respectively (P0.004), but there was no statistical difference between
      the 2 medications in both Zinner index score 1 and score greater than 1 group (P
      0.08, 0.45). Three cases in the famotidine group had successful prophylaxis with
      total time pH > or = 4 more than 80 per cent. Famotidine appeared to have a trend
      toward increasing intragastric pH in critically ill pediatric patients.

PMID- 9623010
TI  - Hysteroscopic resection of submucous myoma: a result of 50 procedures at
      Ramathibodi Hospital.
AB  - We reported an initial result of the safety and efficacy of myomectomies
      performed between September 1994 and June 1997 by the hysteroscopic resectoscope
      in 50 patients at Ramathibodi Hospital. The indications for hysteroscopy and/or
      hysteroscopic myomectomy were menorrhagia in 23, metrorrhagia in 3,
      menometrorrhagia in 2, infertility with abnormal uterine bleeding in 12, abnormal
      uterine bleeding during hormonal replacement therapy (HRT) in 4, and suspected
      submucous myomas detected by ultrasonography and/or sonohysterography in 6
      patients. The mean age of the 50 patients was 39.5 years with a range of 26 to 66
      years. The sizes of the submucous myomas ranged from 1-5 cm. The mean of
      operation time was 32 minutes (range 15-60 minutes). The mean volume of 1.5 per
      cent glycine required for irrigation was 800 with a range of 600-2000 ml, and the
      mean deficit at the end of the operation was 300 with a range of 200-1000 ml. The
      mean estimation of blood loss during the operation was 80 ml with a range of 50
      200 ml. Postoperatively 28 out of 30 patients with menorrhagia had improvement in
      excessive bleeding (93.33%). One patient underwent subsequent hysterectomy due to
      persistent heavy uterine bleeding from recurrent submucous myoma. All patients
      with infertility and patients under HRT had normal menstruation after this
      procedure. 2 out of 12 (16.67%) patients with infertility became pregnant after
      submucous resection. No serious complications occurred. One patient had a
      cervical laceration repaired by simple stitches. One patient had mild
      endometritis responding to outpatient antibiotics. Forty-eight patients were
      discharged from hospital the day after the operation, the remaining two staying
      overnight for observing post-operative bleeding. Our data suggested that
      resectoscopic myomectomy is a safe and effective surgical procedure. The
      procedure offers the advantage to the patients of a shorter hospital stay along
      with a low complication rate. The hysteroscopic approach to the symptomatic
      submucous myoma has dramatically changed the treatment options for patients who
      classically would be offered abdominal myomectomy or hysterectomy.

PMID- 9623011
TI  - Effect of acarbose in treatment of type II diabetes mellitus: a double-blind,
      crossover, placebo-controlled trial.
AB  - This study evaluated the efficacy of acarbose in improvement of metabolic control
      in patients with fairly, well controlled non-insulin-dependent diabetes mellitus
      (NIDDM). Fifteen patients with mean age and duration of diabetes of 57.5 +/- 2.6
      (SE) and 7.5 +/- 1.5 years, respectively were recruited and completed our study
      protocol. This study was a double-blind, crossover, placebo-controlled design
      consisting of two twelve-week treatments of acarbose and placebo separated by an
      eight-week washout period. Acarbose was effective in lowering of 1-hour and 2
      hour postprandial plasma glucose from 251.7 +/- 10.7 and 205.3 +/- 9.1 mg/dl to
      197.4 +/- 7.0 (p = 0.001) and 181.5 +/- 8.5 mg/dl (p = 0.03), respectively.
      Fasting plasma glucose was slightly decreased but without significant change,
      from 150.8 +/- 7.3 to 140.8 +/- 6.1 mg/dl (p = 0.07). Overall glycemic control
      tended to improve during the study period as indicated by the falling of HbA1c
      levels from 7.7 +/- 0.4 to 7.0 +/- 0.2 per cent (p = 0.05). Serum C-peptide both
      fasting and postprandial as well as serum lipids were not affected by acarbose.
      Almost half of the patients treated with acarbose had mild and tolerable
      gastrointestinal adverse effects. In conclusion, acarbose, as combined therapy
      with other oral hypoglycemic agents, was effective in improvement of glycemic
      control particularly postprandial hyperglycemia in fairly, well controlled NIDDM
      patients with mild and acceptable adverse effects.

PMID- 9623012
TI  - Short-term effects of atenolol in patients with dilated cardiomyopathy.
AB  - Dilated cardiomyopathy is a common cause of heart failure with systolic
      dysfunction. Medications used to treat this condition are usually for symptomatic
      relief. We studied the effect of atenolol in heart failure caused by dilated
      cardiomyopathy in a double blinded randomized fashion. There were 17 males and 5
      females. All patients underwent right and left heart catheterization, coronary
      angiography, endomyocardial biopsy, exercise testing and doppler
      echocardiography. By 3 months, atenolol significantly reduced resting and
      exercise heart rate and pulmonary capillary wedge pressure. There was no
      difference in exercise capacity. We conclude from this study that atenolol
      improve hemodynamic condition in patients with dilated cardiomyopathy without
      improving exercise capacity during this short observation period.

PMID- 9623013
TI  - Prenatal sonographic diagnosis of holoprosencephaly.
AB  - The purpose of this series was to describe the sonographic features of fetal
      holoprosencephaly prenatally. The study was undertaken at Maharaj Nakorn Chiang
      Mai Hospital, Chiang Mai University. A total of 12 fetuses with prenatal
      diagnosis of holoprosencephaly were sonographically evaluated and followed-up.
      The study revealed that all showed monoventricular cavity, fused thalami, no falx
      and cavum septum pellucidum. Eight of them were correctly diagnosed
      sonographically in the first two trimesters. Extrafacial anomalies were also
      identified in half of the fetuses and all of them had facial abnormalities.
      Twenty-five per cent (3 cases) had polyhydramnios and only one case had
      oligohydramnios. Chromosome study revealed that 70 per cent had normal
      chromosomes, 30 per cent were aneuploidy, trisomy 13; 2 cases and trisomy 18; 1
      case. In conclusion, this series indicates that ultrasound has a high predictive
      value in the diagnosis of holoprosencephaly. The most valuable clue to the
      diagnosis is the demonstration of the single ventricle. Additionally,
      demonstration of facial abnormalities may add confidence to the diagnosis.
      Conversely, should any of these facial features be serendipitously encountered, a
      careful examination of the intracranial contents is recommended.

PMID- 9623014
TI  - Fatal adenovirus infections in infants probably infected with HIV.
AB  - Adenovirus infections occur commonly in infants and children but are rarely
      fatal. Although immunosuppression has been associated recently with fatal outcome
      of adenovirus infections, reports of major morbidity or mortality caused by
      adenovirus infection in HIV positive patients are infrequent. This is the first
      report on fatal adenovirus infections in presumably HIV-positive infants in
      Thailand. Three infants, aged 4, 8 and 5 months, were hospitalized with diagnoses
      of pneumonia and ARDS, pneumonia with hepatomegaly and ARDS, and pediatric AIDS
      with pneumonia, respectively. All the infants died within a few weeks after
      hospitalization. Serologic tests revealed positive anti-HIV in all three infants.
      Unfortunately, no additional investigation for definite diagnosis of HIV
      infection was employed. Pathological findings from autopsy and post mortem needle
      biopsies revealed adenovirus pneumonia in the first two infants, and massive
      adenovirus infection of the liver in the third infant. Diagnoses were based on
      characteristic light microscopic pathological findings, and demonstration of
      viral particles arranged in crystalline arrays in the nucleus of the infected
      cells by electron microscopy.

PMID- 9623015
TI  - Nutritional potassium status of healthy adult males residing in the rural
      northeast Thailand.
AB  - Sixteen villages from rural areas of 8 provinces in the northeastern region of
      Thailand were randomly selected as study sites. Data on potassium (K) contents in
      24-hour urine and serum samples of 93 healthy adult volunteer males aged 20-50
      years old were completely collected and covered all 3 seasons of the year. The
      method of direct weighing of food was used to assess K intake in 13 subjects. K
      loss through sweat during working (9 hours) in the field was measured in 14
      subjects by soaking their worn-clothes in distilled water after which K contents
      were measured by the flame photometry method. The results showed that the means
      urinary K excretion of 93 subjects were less than that of the cut-off value for
      normal (> or = 30 mmol/day) in all seasons of which 76.71%, 90.71% and 81.02% of
      the urine were categorized as hypokaliuria in the hot, rainy and cold seasons,
      respectively. In the case of serum K of these subjects, though the mean values
      were within a normal limit (> or = 3.5 mmol/l), 36.56%, 34.41% and 29.03% of the
      serum were classified as hypokalemia in the hot, rainy and cold seasons,
      respectively. In the assessment of K intake, it was clearly demonstrated that the
      values in all 3 seasons were much lower than that of the estimated safe and
      adequate daily dietary intake (ESADI) of K for the westerners (1975-5625 mg/day),
      i.e., the means of intake in the hot, rainy and cold seasons were only 807 +/-
      172, 877 +/- 257 and 902 +/- 227 mg/day, respectively. Furthermore, K loss
      through sweat in the cold and the hot seasons were as high as a third (7.4 +/-
      2.4 mmol/day) and a half (11.5 +/- 1.6 mmol/day), respectively, of the urinary
      excretion. Though the total body K contents were not evaluated in this study, our
      results suggest rural people in the northeast region of Thailand may be in a
      state of K deficiency. The severity is probably worsened in the hot season as
      seen from the tendency of decrease in serum K levels among 650 renal stone
      formers and 260 blood donors in this season.

PMID- 9623016
TI  - Falls and their associated factors: a national survey of the Thai elderly.
AB  - Of the 7,713 subjects aged 50 and over in a multistage random sampling national
      survey of Thailand, 4,480 Thai elders aged 60 and over were interviewed in a
      study which aimed to determine rate, characteristics and the associated factors
      of falls in the last six months. Eight hundred and thirty-six elders (18.7%) had
      one or more falls. Female elders (21.5%) fell more often than their male
      counterparts (14.4%). There was no association between age and falls among Thai
      elder population. Most of the falls occurred outside (65%) and during the day
      time (85%). Multiple regression analysis showed that independent factors
      associated with falls among male elder were a bad or fairly bad health, reported
      hypertension, problems with walking in the house, problems with crouching and a
      lack of electricity in the house. Independent factors associated with falls among
      female elders were a bad or fairly bad health, joint problems, illness which made
      her unable to have normal activities during the last year, problems with
      crouching, going to buy food everyday, very lonely feeling, having less than 3
      meals a day, a lack of electricity in the house and living in a Thai style house
      or hut. This study revealed that environmental and intrinsic health factors which
      affected balance and gait were the main factors associated with falls among Thai
      elders. Nutritional status as a contributing factor to falling among elderly
      women was also suggested.

PMID- 9623017
TI  - Hypertension in the elderly: a community study.
AB  - Hypertension in the elderly features differently from its younger counterpart in
      terms of diagnosis, associated condition, atypical manifestation, management and
      complication. Epidemiological study in this increasing age group in the community
      is, therefore, needed. 334 elderly subjects living in various parts of Bangkok
      were randomly recruited by appointment at 7 geriatric day centers situated in
      local health offices of Bangkok Metropolitan Authority. Each subject received
      blood tests before being interviewed and measured by digital sphygmomanometer.
      Blood pressure and heart rate changes were recorded during lying, sitting and
      standing. The prevalence of hypertension was 36.5 per cent, 33.2 per cent were
      already aware of its existence while 3.3 per cent were newly detected by the
      survey. Isolated systolic hypertension, a unique subtype found in the elderly,
      was 4.5 per cent of all or 37.5 per cent among the hypertensive group. The
      associated medical conditions among the case group were diabetes mellitus 22.9
      per cent, hyperlipidemia 13.9 per cent, hyperuricemia 33.3 per cent and heart
      disease 18.0 per cent. As far as postural hypotension is concerned, 14.8 per cent
      of case group whereas 11.3 per cent of the control group were affected. On the
      other hand, the symptom of postural dizziness was found to be 31.1 per cent and
      55.2 per cent in the case and control group respectively. Following the
      statistical logistic regression analysis, the independent associated factors in
      the hypertension group were: history of hyperlipidemia, increased serum uric acid
      and poor heart rate response after standing. These findings, as parts of the
      multiple pathology and potential complications prevalent among this group, should
      be of concern by any physician looking after the elderly.

PMID- 9623018
TI  - The reconstruction twisted wire-screws for internal fixation of two- and three
      part fractures of the proximal humerus.
AB  - Using the implants for internal fixation of the proximal humeral fractures has
      several problems which lead to complications and poor results of the fracture
      treatment. Because there is no suitable implant for internal fixation of the
      fracture. Therefore, the reconstruction twisted wire was developed in 1990 to
      improve the results of the fracture treatment. Between 1990 and 1994, the
      reconstruction twisted wire was used in 31 patients whose ages ranged from 18 to
      90 years. Sixteen patients had displaced two-part surgical neck fractures.
      Fifteen patients had displaced three-part fractures. Postoperative follow-up
      ranged from two and a half years to five years and one month. All fractures
      healed. No avascular necrosis of the humeral head was observed at the follow-up.
      There was temporary subluxation of the shoulder joint in three patients and
      loosening of the screws in two patients with marked osteoporosis. One had a
      rupture of wire between the greater tuberosity and the shaft and loosening of the
      screw at the greater tuberosity and united with 10 degrees varus deformity.
      According to the functional scale proposed by Hawkins, 28 of the 31 patients
      achieved a "good" result and 3 patients had a "fair" result.

PMID- 9623019
TI  - Prevalence of herpes simplex virus infection in patients suspected of genital
      herpes; and virus typing by type specific fluorescent monoclonal antibodies.
AB  - During the period between April 1994 and February 1996, a total of 154 female
      patients who attended the Clinic of Female Sexually Transmitted Diseases, Siriraj
      Hospital with clinical symptoms suspected of genital herpes were investigated for
      herpes simplex virus (HSV) infection by the virus isolation method in Vero cell
      cultures. Swabs from external genital lesions and the cervix from each patient
      were collected separately and used as the clinical specimens for isolation of
      HSV. The virus isolates were identified by indirect immunofluorescence (IIF)
      staining of the infected cell cultures using polyclonal HSV-2 specific antiserum
      which was reactive to common HSV antigens for both types of viruses. Typing of
      HSV was performed by direct IF using monoclonal antibody specific to HSV-1 or HSV
      2. HSV was isolated from 78.6 per cent (121 of 154) of the cases studied; and
      among the infected cases, there were 47.9 per cent (58 of 121) in whom the
      infection involved both external genital lesions and cervixes, and 50.4 per cent
      (61) in whom the infection was limited to external genital lesions only. There
      were 2 cases (1.7%) in whom HSV was isolated from cervixes but not external
      genital lesions. Seventy-five HSV isolates were further subjected to typing. The
      present study showed that HSV-1 was accounted for 18.7 per cent (14 isolates),
      while HSV-2 took the remaining part of 81.3 per cent (61 isolates). The data
      demonstrated an increase in the prevalence of HSV-1 in genital herpes in our
      people.

PMID- 9623020
TI  - Cefoperazone/sulbactam + co-trimoxazole vs ceftazidime + co-trimoxazole in the
      treatment of severe melioidosis: a randomized, double-blind, controlled study.
AB  - A prospective randomized, double-blind, controlled study of
      cefoperazone/sulbactam (cefoperazone 25 mg/kg/day) + co-trimoxazole (trimethoprim
      8 mg/kg/day) vs ceftazidime (100 mg/kg/day) + co-trimoxazole (trimethoprim 8
      mg/kg/day) in the treatment of severe melioidosis was conducted at Srinagarind
      Hospital, Khon Kaen University, Khon Kaen, Thailand, from July 1995 to September
      1996. A total of 84 patients were enrolled in the study. Forty of them (48%) had
      culture-proven melioidosis and were randomly assigned to one of the two treatment
      groups, each group with 20 patients. Two cases (one in each treatment group) were
      excluded from the final analysis due to incomplete data. There was no significant
      difference in the mortality rate between the two groups-16 per cent (3/19) in the
      cefoperazone/sulbactam group vs 21 per cent (4/19) in the ceftazidime group (p >
      0.05). Bacteriological responses of successfully treated patients were similar in
      both groups, and both treatment regimens were well tolerated.
      Cefoperazone/sulbactam + co-trimoxazole can therefore be used as an alternative
      treatment for severe melioidosis. However, to further support this conclusion, a
      study with a larger patient population is needed.

PMID- 9623021
TI  - Anterior decompression and fusion for cervical spondylotic myelopathy.
AB  - The result after anterior decompression and fusion for cervical spondylotic
      myelopathy was retrospectively studied in 49 patients. There were 33 men and 16
      women, their ages ranged from 27 to 82 years (average 53.7 years). The most
      common level of involvement was C5-6, followed by C3-4. Walking difficulty of
      various degrees in combination of numbness and weakness of upper limbs were the
      most common presenting symptoms. The duration of pre-operative symptoms ranged
      from 1 month to 10 years (average 6 months). The functional results at final
      follow-up were evaluated using the author's grading criterias. Mean follow-up
      time was 5.3 years (range 1-10 years). Forty-six patients were neurologically
      improved at various degrees, three cases were unchanged, none had neurological
      deterioration. There was no time limit of neural recovery as to the duration of
      disease prior to surgery. The potential cord recovery might be partly affected by
      age, duration of the symptoms, and pre-operative functional grade.

PMID- 9623022
TI  - The potential alveolar hazard of carbon dioxide laser-induced smoke.
AB  - Carbon dioxide laser is a continuous wave laser, it is well known for its
      capacity of tremendous smoke production while contact with tissue. Smoke may
      cause nausea, vomiting, headache and airway irritation. Smoke particles 0.5-2
      micrometers in diameter usually travel down the tracheobronchial tree and lodge
      in the alveoli posing a health hazard. The objectives of this study were to
      evaluate possible health hazards of carbon dioxide laser smoke in the operating
      room environment, by determining the size and density of smoke particles also
      determine the efficacy of surgical masks as a smoke protectant. Ten fresh
      specimens of papillomatous tissue obtained from the patients were lased by carbon
      dioxide laser in a continuous mode. The plume generated was collected by 0.45
      micrometers pore size microfilter which was attached to the tip of a suction hose
      connecting the smoke evacuator. The effectiveness of 2 types of commonly used
      surgical masks were also determined by trapping the smoke after passing through
      each mask using the same model. Smoke particles were evaluated by scanning
      electron microscope. The smoke particle density of microfilter that directly trap
      plume averaged 6 particles/mm2, particles ranging in size from 0.5-27
      micrometers, of which 70 per cent were 0.8 micrometers. For the particles trapped
      after passing through both cotton and paper surgical mask, the size were ranging
      from 1.6-37 micrometers where 65 per cent were 3.7 micrometers and the particle
      density average 2.7/mm2. We concluded that the smoke particles derived from
      carbon dioxide laser application are within the alveolar hazard zone. The
      conventional surgical masks may not be an effective tool against laser smoke
      hazard.

PMID- 9623023
TI  - Comparison of ketoprofen and morphine for post-operative analgesia in orthopaedic
      patients.
AB  - A prospective, open label, randomized study to compare efficacy of intramuscular
      administration of ketoprofen and morphine for post operative analgesia in
      elective orthopaedic surgery was performed in 50 patients. The procedures were
      open reduction and internal fixation of long bone fractures (26 cases), hip
      replacement (9 cases) and spinal surgery (15 cases). Pain intensity and pain
      relief in both groups were evaluated at 1, 3 and 6 hours post-injection. There
      was no significant differences in pain relief of both groups (P = 0.05). The side
      effects of intramuscular ketoprofen were encountered in only 8 per cent.
      Ketoprofen injection is an alternative for post operative pain relief.

PMID- 9623024
TI  - Rehabilitation in uncomplicated myocardial infarction at Ramathibodi Hospital: 5
      years follow-up.
AB  - Prospective study: 44 cases of post acute uncomplicated myocardial infarction
      were divided into 2 groups: control and exercise groups. The control group
      consisted of 22 patients, 35-74 years (mean 63.25) and exercise group consisted
      of 22 patients, 33-71 years (mean 54). The exercise test was performed at 5 METS
      predischarge then an exercise program conducted by a physiatrist (physician
      specialized in physical medicine and rehabilitation) but was not given in control
      group. The exercise test was repeated 12-weeks post discharge with results
      showing a remarkable difference between the 2 groups statistically. Also, after a
      5 year follow-up, the exercise group were living, normally, 77 per cent versus
      only 30 per cent in the control group. Death in the exercise group and the
      control group was 5 per cent and 45 per cent respectively.

PMID- 9623025
TI  - Triple diagnosis in carcinoma of the breast: a replacement for open biopsy.
AB  - Using the combination of clinical diagnosis, mammography and fine-needle
      aspiration cytology (FNA) as a "triple diagnosis" to guide management of
      carcinoma of the breast, we retrospectively reviewed 46 patients with FNA
      diagnosis of carcinoma of the breast in Ramathibodi Hospital from 1993 to 1995.
      Pathological diagnosis was available in 36 cases and used as a gold standard.
      Clinical diagnosis alone was accurate in 28 of 36 cases. Mammography was
      available in 24 cases of which the diagnosis was accurate in 22 cases. Triple
      diagnosis was available in 19 cases and all were accurate. Using this approach
      and review of the literature, we suggest that triple diagnosis could replace an
      open biopsy in diagnosis of carcinoma of the breast.

PMID- 9623026
TI  - Nomogram of nuchal fold thickness of Thai fetuses.
AB  - The aim of the study was to establish normal values of nuchal fold thickness
      during 14-21 weeks of pregnancy. Three hundred Thai pregnant women before 12
      weeks of gestation were recruited. Gestational age was determined by last
      menstrual period and confirmed by crown-rump length. Subjects with date-size
      discrepancy of more than 7 days were excluded from the study. Nuchal fold
      thickness was measured twice, first during 14-17 weeks, and then during 18-21
      weeks. Five hundred and nine measurements were obtained. Nomogram of nuchal fold
      thickness was constructed. Mean values of nuchal fold thickness increased
      steadily from 2.59 +/- 0.77 millimeters (mm) at 14 weeks to 4.12 +/- 0.98 mm at
      21 weeks. Average rate of increase were 0.22 mm per week. In conclusion, nuchal
      fold thickness increased with advancing gestational age from 14 to 21 weeks of
      pregnancy. Different normal cut-off levels for each gestational week may be more
      appropriate for screening of fetal Down syndrome in Thai pregnant women.

PMID- 9623027
TI  - In vitro activity and clinical evaluation of cefixime in urinary tract infection.
AB  - Thirty-five women with uncomplicated acute lower urinary tract infections proven
      by significant pre-treatment bacteriuria (> or = 10(5)CFU/ml) were treated with
      an oral dose of 100 mg cefixime twice a day for seven days. Thirty five patients
      included in this study were checked for response to treatment on the last day of
      therapy, 7-14 days and 4 weeks post therapy. The clinical response and bacterial
      eradication rate for cefixime were 91.4 per cent (32/35). The infecting
      organisms, E. coli and Proteus mirabilis, were inhibited at MIC90 = 0.5 and < or
      = 0.03 microgram/ml, and MBC = 1 and 0.06 microgram/ml respectively. No adverse
      events were found in this study.

PMID- 9623028
TI  - Short-term biological impact on teenage mothers and their babies.
AB  - This prospective study covered a one year period between between June 1994 and
      August 1995 and included 104 cases of teenage mothers and 98 control adult
      mothers. The purpose was to assess the short-term biological impact on teenage
      mothers and their babies in Thailand by comparing teenage mothers-age < or = 18
      years old and adult mothers-age 20-35 years old. The mean age of the teenage
      mothers and adult mothers was 16.75 +/- 0.97 and 26.67 +/- 2.88. The result
      demonstrated that there was no significant difference in the short-term
      biological effect on mothers and their babies.

PMID- 9623029
TI  - Functional skills after rehabilitation for patients with spinal cord injury.
AB  - This follow-up study evaluated the functional skills of 151 spinal cord injury
      persons after comprehensive in-patient rehabilitation. The mean age of subjects
      was 34.1 years, consisting of 132 males and 19 females. The results indicated
      that the level of self-care achieved after rehabilitation was maintained by the
      majority of rehabilitants. The ability of quadriplegics to eat demonstrated the
      most deterioration, while the ability of quadriparetics and paraparetics to
      ambulate significantly improved. However, rehabilitants with complete thoracic
      cord injury were unable to maintain functional ambulation.

PMID- 9623030
TI  - The incidence of K-ras codon 12 mutations in cholangiocarcinoma detected by
      polymerase chain reaction technique.
AB  - In the study, to analyse a K-ras oncogene mutated at codon 12 in 24 patients with
      cholangiocarcinomas, four (16.67%) of them contained this point mutation. One of
      4 was peripheral and the others were hilar tumors. There was no significant
      relationship between mutation and clinical features in terms of age, sex, endemic
      area, tumor location, tumor grading and pathological features. In our study, the
      incidence of K-ras codon 12 mutation in Thai patients with cholangiocarcinoma was
      lower than that found in British and Japanese patients. The discrepancy of
      incidence and type of the mutations, in different races and environment probably
      indicates that there is/are different etiologic mechanism(s) in the pathogenesis
      of cholangiocarcinoma.

PMID- 9623031
TI  - Efficacy and tolerability of risperidone in chronic schizophrenic Thai patients.
AB  - Risperidone is a novel serotonin-dopamine antagonist antipsychotic in a class of
      benzisoxazole derivative which has been shown to be effective in reducing
      psychotic symptoms in schizophrenia. The study was designed as perspective, 8
      week, multicenter, open label study in schizophrenic patients from 6 psychiatric
      hospitals. One hundred and twenty cases were recruited and 105 patients completed
      the study. The average total PANSS score at the baseline was 90.6 (range 60-133).
      Patients were evaluated with quantitative rating scales for the efficacy (PANSS
      score) and extrapyramidal rating scale at week 4 and 8 after starting risperidone
      treatment. The titrated dose of risperidone was given to the patients with the
      final dose of 6 mg risperidone throughout the study period. At week 4, the
      average PANSS score was significantly reduced to 73.4 (p < 0.05). The average
      PANSS score at week 8 was further declined to 61.9 which was significantly
      different (P < 0.05) from the baseline. Seventy-eight cases (74.3%) were
      classified as responders (those patients showing more than 20 per cent decrease
      in PANSS score). Extrapyramidal side effect was occurred in some patients, but
      usually mild and tolerable. However twenty-four patients (22.9%) required
      medications for this side effect. Other adverse reactions were insomnia found 15
      cases (14.3%), elevated hepatic enzyme 5 cases (4.8%) and weight gained 2 cases
      (1.9%). Our data suggested that risperidone is effective and well-tolerated in
      chronic schizophrenic Thai patients.

PMID- 9623032
TI  - Nasopharyngeal tuberculosis.
AB  - Nasopharyngeal tuberculosis used to be a common disease in the upper
      aerodigestive system. Before 1920, 1.4 and 6.5 per cent of all adenoids and
      tonsils removed from asymptomatic patients were infected by tuberculosis. After
      the introduction of antituberculous chemotherapy and BCG vaccination, this
      disease was considered uncommon and sporadic cases were reported in the medical
      literature. Recently, tuberculosis has begun to increase again due to the high
      global HIV-infected rate and antituberculous drug resistance among these people.
      To describe and highlight the clinical features of this condition, fifteen Thai
      patients (7 males and 8 females) from the Department of Otolaryngology, Siriraj
      Hospital, Bangkok, Thailand were reviewed. Cervical lymphadenopathy was the most
      common presenting symptom in our series (93.34%), 11 of them were classified as
      primary nasopharyngeal tuberculosis and most had abnormal nasopharyngeal findings
      by mirror examination except 2 cases. Although all had histopathological
      confirmation of nasopharyngeal tuberculosis, sometimes problems occur in the
      diagnosis between this disease and nasopharyngeal carcinoma, which are also
      common among Oriental people in many of their clinical similarities. Therefore
      routine nasopharyngeal biopsy is considered justified and diagnostic.

PMID- 9623033
TI  - Metabolic and immune effects of dietary arginine, glutamine and omega-3 fatty
      acids supplementation in immunocompromised patients.
AB  - To evaluate the nutritional, metabolic and immune effects of dietary arginine,
      glutamine and omega-3 fatty acids (fish oil) supplementation in immunocompromised
      patients, we performed a prospective study on the effect of immune formula
      administered to 11 severe trauma patients (average ISS = 24), 10 burn patients
      (average % TBSA = 48) and 5 cancer patients. Daily calorie and protein
      administration were based on the patient's severity (Stress factor with the range
      of 35-50 kcal/kg/day and 1.5-2.5 g/kg/day, respectively) Starting with half
      concentration liquid immune formula through nasogastric tube by continuous drip
      at 30 ml/h and increasing to maximum level within 4 days. The additional energy
      and protein requirement will be given either by parenteral or oral nutritional
      support. Various nutritional, metabolic, immunologic and clinical parameters were
      observed on day 0 (baseline), day 3, 7, and 14. Analysis was performed by paired
      student-t test. Initial mean serum albumin and transferrin showed mild (trauma)
      to moderate (burn and cancer) degree of malnutrition. Significant improvement of
      nutritional parameters was seen at day 7 and 14 in trauma and burn patients.
      Significant increase of total lymphocyte count (day 7, P < 0.01), CD4 + count
      (day 7, p < 0.01), CD8 + count (day 7, p < 0.0005 & day 14, p < 0.05), complement
      C3 (day 7, p < 0.005 day 14, p < 0.01), IgG (day 7, and 14, p < 0.0005), IgA (day
      7, p < 0.0005 & day 14, p < 0.05), in all patients. C-reactive protein decreased
      significantly on day 7 (p < 0.0005) and day 14 (p < 0.005). 3 cases of burn wound
      infection, one case of UTI and one case of sepsis were observed. Two cases of
      hyperglycemia in burn, 3 cases of hyperbilirubinemia in trauma, 10 cases of
      elevated LFT (5 trauma/5 burn), and one case of hyponatremia in cancer patients
      were observed. Two cases of nausea, 4 cases of vomiting, 5 cases of diarrhea (< 3
      times/day), 2 cases of abdominal cramp, 1 case of distension were observed. The
      feeding of IMMUNE FORMULA was well tolerated and significant improvement was
      observed in nutritional and immunologic parameters as in other immunoenhancing
      diets. Further clinical trials of prospective double-blind randomized design are
      necessary to address the so that the necessity of using immunonutrition in
      critically ill patients will be clarified.

PMID- 9623034
TI  - Hearing impairment in Thais due to sport shooting: a preliminary report.
AB  - Ninety one sportshooters from several sportshooting clubs ranging in age from 20
      49 and 85 control subjects were carefully examined for hearing ability. The male
      and female ratio was 10.37:1. It was found that 9.34 per cent of the subjects
      were suffering from hearing impairment at the level of 3,000-8,000 Hertz. At most
      frequencies the mean decibel between the groups of shooters (1-5 years, 5-10
      years, more than 10 years) was significantly different, with the right ear being
      significantly more impaired than the left ear (alpha = 0.1). At all frequencies
      the mean decibel level for the control group was significantly different from
      that for the sportshooters (alpha = 0.1). In conclusion, it is the responsibility
      of the National Environmental Board on Noise Pollution, the Royal College of
      Otolaryngologists of Thailand and other related organizations should be much more
      aggressive in educating sportshooters with regard to protecting their ears
      against acoustic trauma.

PMID- 9623035
TI  - A randomised controlled trial of regular surveillance in Thai elderly using a
      simple questionnaire administered by non-professional personnel.
AB  - To test the benefits of regular surveillance of the elderly at home using a
      simple-questionnaire, 142 randomly selected subjects aged 70 years or over and
      living in a slum area of Bangkok were recruited and were designated as cases (n =
      70) and controls (n = 72). At the beginning of the study period all subjects were
      visited and their characteristics, including morbidity data, activities of daily
      living (Barthle ADL Index, Chula ADL Index) and number of falls during the last
      three months, were collected. Over three years the cases were visited every three
      months, in their own home, by non-professional personnel. They and/or their care
      givers were interviewed using a short questionnaire designed for the home
      visiting programme. The elderly who had problems according to the criteria were
      visited and assessed by nurses and/or a geriatrician. Appropriate management was
      provided to these elderly. After three years, all subjects were visited and
      outcome data were collected. Rates of service use among the cases were higher
      than among the controls but there was not a statistically significant difference.
      The rate of declining in Chula ADL Index score of the cases was significantly
      less than that of the controls. (p < 0.05) There was no statistically significant
      difference between other main outcomes of the case and control groups. However,
      regular home visiting of old people at home by non-professional personnel using a
      simple questionnaire is a practical way for community care of the elderly
      population living in poor areas.

PMID- 9623036
TI  - Reference ranges of reticulocytes in adults.
AB  - According to the International Committee for Standardization in Haematology
      (ICSH), we determined the reference values for reticulocytes using an automated
      blood cell analyzer Technicon H*3 RTC in 200 healthy adult blood donors, aged
      between 17 and 60 years, 100 of whom were male and 100 female. The parameters
      included reticulocyte count, and its corpuscular indices; mean reticulocyte
      corpuscular volume (MCVr), mean reticulocyte corpuscular hemoglobin concentration
      (CHCMr), mean reticulocyte hemoglobin content (CHr), reticulocyte distribution
      width (RDWr), reticulocyte hemoglobin distribution width (HDWr) and reticulocyte
      corpuscular hemoglobin concentration distribution width (CHDWr). The reference
      ranges were established by setting the reference limits at two standard
      deviations from the arithmetic reference mean.

PMID- 9623037
TI  - Harlequin baby: a case report.
AB  - Harlequin fetus is a rare and the most severe form of congenital ichthyosis. Most
      of the infants die within a few weeks after birth due to sepsis and respiratory
      difficulties. The case of a female harlequin baby is reported. The baby survived
      because of good neonatal intensive care, topical emollients and oral etretinate.
      Now she is over three years old and the skin developed into congenital non
      bullous ichthyosiform erythroderma. Unfortunately she had delayed growth and
      development. This is the first case report of a harlequin fetus in Thailand that
      had prolonged survival.

PMID- 9623038
TI  - Congenital localized multiple fibromatosis: a case report.
AB  - Clinical, histopathologic and electronmicroscopic findings in a case of
      congenital localized multiple fibromatosis of interscapular region are presented.
      This 10 year-old Japanese girl developed this lesion since she was 3 weeks old,
      metastases have never been observed. The histological and electron-microscopic
      features point to the hamartomous origin of this tumor with partial
      differentiation of its cells towards myofibroblasts and atypical fibroblasts. The
      differential diagnosis from other soft tissue tumors in infancy and early
      childhood is discussed.

PMID- 9623039
TI  - Successful pregnancy in a case of azoospermia from congenital bilateral absence
      of vas deferens (CBAVD) using percutaneous epididymal sperm aspiration (PESA) and
      intracytoplasmic sperm injection (ICSI).
AB  - In men with obstructive azoospermia, bypass surgery would obviously be the most
      acceptable form of treatment as it gives the couple an opportunity to conceive
      naturally. However, when this has failed to restore patency or when surgery is
      not feasible (congenital absence of vas), fertility treatment using spermatozoa
      aspirated from the epididymis should be considered. Percutaneous epididymal sperm
      aspiration (PESA) is more acceptable to patients than micro epididymal sperm
      aspiration (MESA) because it eliminates the requirement for a general
      anaesthetic, post-operative pain, and the risk of haematoma formation, thus
      allowing a rapid return to normal activity of the husband. To our knowledge, this
      is the first reported case in Thailand where a pregnancy resulted in a couple
      whose infertility was due to azoospermia from the congenital absence of vas
      deferens. Spermatozoa collected through PESA were used in ICSI to achieve
      fertilization. The PESA technique, due to its simplicity is the choice of
      treatment for obstructive azoospermia.

PMID- 9623040
TI  - [Increasing possibility to detect disease disposition. Genetic information
      regulated by law?].

PMID- 9623041
TI  - [Minilaparotomy is still an experimental technique. Its value must be evaluated
      by randomized studies].

PMID- 9623042
TI  - [Gradual "reconstruction" of the reward system. Neurochemical changes a possible
      cause of multidependence].

PMID- 9623043
TI  - [Saving on continuing education is objectionable].

PMID- 9623044
TI  - [What is cost effectiveness?].

PMID- 9623045
TI  - [Postprandial hypoglycemia--a new indication of acarbosis?].

PMID- 9623046
TI  - [Hippocratic oath and perspective of the authorities].

PMID- 9623047
TI  - [More distinct rules for physician-patient relations are necessary].

PMID- 9623048
TI  - [Adequate analgesia in circumcision of boys is a matter of course].

PMID- 9623049
TI  - [Minilaparotomy is a careful method in right colon tumor surgery].
AB  - In a series of 47 patients, right colon tumours were treated surgically with a
      minilaparotomy approach, entailing a skin incision of less than 10 centimetres.
      The procedure allows appropriate oncological management of the tumour, and is
      associated with a mild postoperative course and a rapid recovery and resumption
      of normal life. The short-term outcome in this series has been promising, and the
      minilaparotomy approach would thus appear to be an attractive alternative to
      traditional open surgery of the right colon.

PMID- 9623050
TI  - [Atherosclerosis not caused by overindulgence only. Infection may be a risk
      factor for cardiovascular disease].
AB  - The importance of vascular inflammation in the atherosclerotic process is
      receiving increasing attention. Several infections have been linked with
      cardiovascular disease and atherogenesis, and the risk of cardiovascular
      manifestations has been found to be increased in the presence of autoimmune
      diseases such as rheumatoid arthritis or systemic lupus erythematosus.
      Inflammatory cytokines have been shown to induce changes in lipid metabolism and
      endothelial function, which may result in arterial disease. These recent advances
      in our knowledge may provide a basis for the development of new strategies for
      the prevention and treatment of atherosclerosis and cardiovascular disease.

PMID- 9623051
TI  - [Venous insufficiency and leg ulcers are common and expensive problems. Improved
      diagnosis and treatment help more patients].

PMID- 9623052
TI  - [A medical-historical pause].

PMID- 9623053
TI  - [In the tract of migration and exile: psychosocial consequences of a changed
      family structure].

PMID- 9623054
TI  - [Incorrect dosage of anticoagulant therapy is expensive. Could self-monitoring
      improve the situation?].
AB  - In Sweden, the use of anticoagulants has increased by 30 per cent during the
      1990s, approximately 45,000 (5.3/1000) of the population being on continuous
      treatment in 1995. At present, the effect of anticoagulant treatment is monitored
      at hospitals and out-patient clinics, and by general practitioners. In very few
      cases is it monitored by patients them-selves. In the article are presented the
      results of an analysis of published figures, performed to elicit the frequency of
      anticoagulant controls, that of serious haemorrhages occurring in conjunction
      with therapeutic anticoagulant levels above the recommended INR (international
      normalised ratio) ranges, and that of thrombo-embolic events occurring in
      conjunction with levels below the INR ranges, and the corresponding estimated
      costs of insufficient control. Mean overall exposure to increased risk of
      haemorrhage was approximately 2,300 patient-years (range, 670-4,050), and that to
      increased risk of recurrent thrombosis or embolism 4,300 patient-years (range,
      1,013-7,650). The mean estimated cost of haemorrhagic complications was SEK 34 m
      (range, 11.6-54.7), and that of thrombo-embolic complications approximately SEK
      49 m (range, 22.6-73.9) (1 GBP = 13.5 SEK, 1 USD = 7.4 SEK). Part of these costs
      could have been avoided by reducing the duration of insufficient control. Future
      research will show whether self-monitoring would achieve this.

PMID- 9623055
TI  - [Physicians behind sterilization laws already before Hitler's takeover.
      Development of German medicine in a long-term perspective].

PMID- 9623057
TI  - [Education of personnel in the diagnosis and therapy of bronchial and pulmonary
      carcinoma].
AB  - The education of staff that works on diagnostics and treatment of bronchopulmonal
      carcinoma should be continuous process. It has to include staff from preventive
      health care structures and also pedagogists, social welfare workers,
      psychologists and others who make contact with citizens, and educational
      institutions and so on. In other hand, education must include all health
      professionals who work on early detection and early treatment of patients with
      bronchopulmonal carcinoma. There is a problem to find the best way for conducting
      education. It is suggested that it should be duty of a team of different experts.
      Team members would be chosen and structured according to criteria which would be
      by consensus. The procedure of reform must be conducted methodologically
      correctly and according to common fixed criteria. There is tendency that some
      steps of education reform on the High school of Medicine and education of the
      third level have to be done immediately, in transitive time, because the vacuum
      and failures in education make the errors through the whole life. It is very
      important to point out underlay the special and the addition education, the
      making plans and programs of the staff education and suggestion of emergency
      actions of reform of education on lung diseases in transitive period, regard of
      war suffering, human resources, equipment and technical possibilities.

PMID- 9623058
TI  - [Prevention of bronchial and pulmonary carcinoma].
AB  - Malignant neoplasms, and especially CA of bronchi and lungs, are major health and
      social problem, regard of frequency, as well as duration of treatment, and place
      among leading causes of death. Among all types of malignant neoplasms, CA of
      bronchi and lungs correlates directly with tobacco consumption and environmental
      risk'factors, such as industrial pollutants of the human micro and macro
      environment. Author presents specific preventive programmes of CA of bronchi and
      lungs, as well as the evaluation programme of integrated national activities in
      reduction of malignant neoplasms.

PMID- 9623059
TI  - [Smoking as a risk factor in the onset of bronchial carcinoma].
AB  - With regard to proved fact that smoking plays very important role in appearance
      of the lung cancer, prevention of the lung cancer goes together with fight
      against smoking. Since smoking is narcotism, prevention of smoking is the only
      solution of the problem of smoking, respectively that is the only prevention of
      bronche-cancer. For those who continue smoking, there is some suggestions, such
      as: not to smoke the last third of cigarette, do not inhale smoke deeply, to
      reduce number of consumed cigarette, and to have regularly examinations, i.e. to
      have X-ray examination of the lung on the six months basis.

PMID- 9623060
TI  - [Epidemiologic aspects of bronchial carcinoma].
AB  - In Bosnia and Herzegovina incidence with average morbidity is 16, inhabitant per
      100,000. There is permanent increase in incidence of bronchial cancer.
      Epidemiological risks influence on the increase of morbidity of this disease.
      According to the some research it was discovered that influence of smoking is an
      important factor when causing bronche-cancer. In 79.48% cases, patients are
      smokers, 5.12% are former smoker and only 15.13% of the patients have never
      smoked. Due the air-pollution in some industrial environments there is increase
      of cancer of bronchial.

PMID- 9623061
TI  - [Anatomy of the lymphatic vessels and lymphatic tissue of the lungs and pleura].
AB  - The lymph system in the lungs and chest has a very important role in disease
      spreading and recovery. No organ in lymph can compare to lungs regard of lymph.
      Two lymph nets exist in the lung superficially and profoundly, and also mutually
      communicate at hilus level and interlobular septum. On profoundly level of the
      net lymph vessel exist three lymph nets around bronchus, artery and veins. The
      lymph tissue placed in lung is particularly characteristic for children. The
      regional lymph tiejof the lungs can be divide on intrapulmonal and extrapulmonal.
      According to lymph drainage from lung we are talking about three territories:
      upper, medial and lover which are not coincides with lobar division. The
      capillary lymph net of the parietal pleura accumulate on subpleural net, from
      were leaving to regional lymph's nodes.

PMID- 9623062
TI  - [Histological structure of the distal segment of the respiratory tract].
AB  - The respiratory system consists of morphologically and functionally distinct sub
      divisions-the air-conditioning part and respiratory portion is were O2 and CO2
      exchange actually occurs across the delicate, very thin walls of the pulmonary
      alveoli. The final bifurcation of bronchiole yields terminal bronchiole. The
      epithelium is gradually reduced from ciliated columnar in the larger bronchioles
      to ciliated or non-ciliated low cuboidal in the terminal segment. Here non
      ciliated Clara cells are plentiful. Only under EM one can clearly identify the
      lining cells of the alveoli: type I are squamous pneumocytes, type II are large
      granular alveolar cells and macrophages (dust cells). The hallmarks of
      pneumocytes type II are the numerous osmiophilic, lamellated inclusion bodies. In
      TEM there is evidence connecting these bodies with the production of stabilizing
      surface active material, which prevents the collapse of the alveoli; colled
      surfactant, different from that of the Clara cells.

PMID- 9623063
TI  - [Morphology of lung cancer].
AB  - Giving a final diagnosis of lung cancer, is only possible due to the detail
      microscopy analysis of large samples, where "small biopsies" or cytological
      samples can be used as working diagnosis. Modern tumor diagnostics strictly
      includes TEM and immunohistochemistry. Also, in contemporary literature there are
      a lot of classifications in order to determinate nature of tumor and enlighten
      its causes, to describe it's biological behaviour and to predeterminate value and
      type of medical intervention. There is classification on bronchi cancer and lung
      adenomatosis bronchi-alveolar cancer). Another classification is based on
      microscopic view, so there are have hilus (central), lungs and periphery type.
      Microscopic classification has bigger significance and is based on type of tumor
      cell. Nature of malign lung tumor can be defined in greater details by
      immunohistochemical and electron microscopic research.

PMID- 9623064
TI  - [Symptomatology in bronchial carcinoma].
AB  - The essential characteristic on carcinoma of the lung are presented. With 100
      patients with Ca bronche diagnosed by pathology, we evaluated the significance of
      the clinical manifestation of this disease. The most frequent symptoms are: cough
      (83%), pectoral pain (65%), dyspnoea (60%), temperature (57%), haemoptysis (29%).
      It is presented the etiopathogenesis of these symptoms. The significance of
      history and physical findings in forming a preliminary diagnosis is analysed.
      This in turn is the basis for the programming examinations and diagnostic
      procedures.

PMID- 9623065
TI  - [Radiologic diagnosis of bronchogenic carcinoma].
AB  - The staging classifications and basic characteristics of five cell types of
      bronchogenic carcinoma, as well as the sensitivity and specificity of plain
      radiography, CT and MRI in the staging of central and peripheral bronchogenic
      carcinoma have been presented. In conclusion, it was emphasized that CT, US and
      MRI have considerably improved diagnostics of bronchogenic carcinoma, although
      there are still difficulties regarding their sensitivity and specificity in the
      assessment of malignant mediastinal and hilar adenopathy, pleural and chest wall
      infiltration and tissue categorisation of the solitary pulmonary nodule. Finally,
      two schemes for evaluation of the patients with central bronchogenic carcinoma
      and solitary pulmonary nodule have been recommended.

PMID- 9623066
TI  - [CT aspects of brain metastases in bronchial carcinoma].
AB  - Twenty patients of 210 with the brain metastases with diagnosed bronchogenic
      carcinoma were analysed, according to existing morphological criteria of computed
      tomography (CT), in correlation with pathohistologically findings (PHD) of
      primary tumor. Multiple lesions and perifocal edema as the main CT features of
      metastatic disease of the brain were confirmed. Some details like increased
      frequence of the solitary forms and uncharacteristic perifocal edema were
      emphasized. Also, some differential diagnostic possibilities with the brain
      metastases were considered.

PMID- 9623067
TI  - [Frequency of abdominal metastases in bronchogenic carcinoma].
AB  - In the retrospective study, 210 patients with diagnosed bronchogenic carcinoma
      have been managed during four years period. In this group there were 23 patients
      with abdominal metastases; 21 with liver metastases and 2 with adrenal
      metastases. Abdominal metastatic lesions were diagnosed by ultrasonography and
      CT. With the patients with liver metastases, 4 of them had solitary lesion, and
      remaining 17 patients had multiple metastases. In the same group, 8 patients had
      planocellulary cancer, 5 microcellulary cancer, 3 had confirmed anaplastic
      cancer, and 5 patients were without pathohistologically confirmed findings. In
      one case of adrenal metastases planocellulary cancer was found, and in another
      case of adrenal metastases pathohistological diagnosis was unknown. The authors
      concluded that ultrasonography and CT were the methods of choice in diagnostics
      liver and adrenal glands metastases with the patients with bronchogenic
      carcinoma.

PMID- 9623068
TI  - [Frequency of bone metastases in bronchogenic carcinoma].
AB  - Medical findings of 210 patients with bronchogenic cancer in the four years
      period of time were elaborated retrospectively. Bone metastases were found with
      27 (13.8%) patients. Diagnostic radiologic procedure were plain radiography and
      CT. The frequency, the localization and the distribution of bone metastases
      depending on pathohistological diagnosis were presented. The bone metastases were
      the most frequent (27 patients or 13.8%) compared to metastases of abdomen (23
      patients or 10.9%) and brain (20 patients or 9.5%). Out of the total number of 27
      (100%) patients with bone metastases, 9 (33.3%) of them have got solitary
      metastases, and 18 (66.7%) patients have got multiple metastases. Large number of
      bone metastases were located at spine, and very rarely at radius, ulna and
      scapula. It was shown that the small cell carcinoma with the most malignant
      potential was found with 3 (11.1%) patients only. It can be explained by the fact
      that a large number of patients hadn't got pathohistological diagnosis (13
      patients or 48.2%). As a conclusion, the high percentage of patients without
      final diagnosis is a result of insufficient diagnostic procedures, the
      radiological ones due to a lack of technical means and not performing biopsy and
      autopsy.

PMID- 9623069
TI  - [Bronchoscopy and biopsy methods in the diagnosis of bronchial carcinoma].
AB  - A review of today possibilities of bronchoscopy in diagnosis of bronche cancer
      was given in this paper. Endoscopic findings at bronche cancer were classified,
      and other biopsy methods during bronchoscopy were reviewed. A review of other
      diagnostic methods of bronche cancer was given: needle blind biopsy of pleura,
      percutaneous aspirated needle biopsy of lungs. The possibilities of treatment
      local endoscopic changes were given: cryotherapy and laser-therapy.

PMID- 9623070
TI  - [Surgical treatment of pulmonary carcinoma].
AB  - In this article we report the historical movement and the contemporary state of
      the surgical treatment of lungs carcinoma. We especially point to importance of
      early diagnosis of lungs carcinoma, in order to get right time for the radical
      resection. The TNM classification has a very important. But, some attitudes of
      the right time of the radical resection are for the next discussions and
      investigations.

PMID- 9623071
TI  - [Importance of exploratory thoracotomy in the diagnosis of malignant neoplasms of
      the lung].
AB  - Role and importance of the explorative thoracotomy in diagnostics of malignant
      neoplasmas of the lung have great value. Among other diagnostic procedures
      explorative thoracotomy has an advantage because of visualization of process and
      possibility of the biopsy "extempore". As each diagnostic procedure, explorative
      thoracotomy has its own deficiencies because the procedure is aggressive, related
      to possibility of the postoperative complications, and because of these problems
      explorative thoracotomy is ultimative method in diagnosis of malignant neoplasmas
      of the lungs.

PMID- 9623072
TI  - [Personal experience in the treatment of single brain metastases and comparison
      with current neurosurgical approaches].
AB  - Single metastases of the brain treated from January 1989 do December 1992 at the
      Neurosurgical Clinic in Sarajevo have been presented. Our approach and selection
      of patients have also been showed. We have compared our work with current
      neurosurgical treatment of metastases of the brain. The lung have been the source
      of the single brain metastases in 67%. Anaplastic carcinoma have been the most
      common pathohistological diagnosis. Metastases have been found in the cerebrum in
      80% cases. Percent of the males patients have been 67%. The most frequently,
      patients have been ages 40-59. The single brain metastases with good general
      condition of the patient have been operative treatment indication. Operative
      mortality have been 12%. All patients have been treated by radiotherapy after
      operating. Contrast-enhanced CT of the brain have used to make preoperative
      diagnosis.

PMID- 9623073
TI  - [Chemotherapy of bronchial carcinoma].
AB  - Antitumorous therapy comprises certain drugs of different origin. Scientific
      activities in discovering new antitumorous substances and making therapeutic
      schemes for achieving optimal effects have been presented worldwide for decades.
      The therapeutic effects are in the most cases very slight. Cured patients are
      rare, but this sometimes occurs. Partial reducing of tumorous infiltrate and its
      progression interruption appear more frequently. Therapeutic effectiveness
      manifests itself in improving of life-time quality. Regard of drug non
      indifference and its limited effectiveness, the doctors must wonder about very
      sensitive question i.e. how much the drug administration will be of benefit or it
      will diminish this low life-time quality. Experts teams decide usually about drug
      administration. Early diagnosis is the "imperative" of present possibility
      appearance of symptoms to definitive treatment. The time from the beginning of
      the first therapy must be as short as possible if we wouldn't like to loose on
      therapy effectiveness.

PMID- 9623074
TI  - [Clinico-pharmacologic aspects of therapy of lung cancer].
AB  - Antineoplastic agents called also cytostatics or cytotoxic agents have been used
      as modality in the treatment of lung cancers. Of all the histologic types of lung
      cancer, small lung cancer is the most sensitive to chemotherapy, although overall
      prognosis of patients with this cancer is quite poor. Now we have many
      combinations of cytotoxic agents and enough clinical experience, based on recent
      insights into the clinical behavior of lung carcinoma.

PMID- 9623075
TI  - [Evaluation of polychemotherapy of small cell lung carcinoma].
AB  - Small cell carcinoma of the lung is a separate clinical and pathological entity
      with characteristics of early and wide dissemination, and also great sensitivity
      on chemotherapy and radiotherapy. We evaluated results of therapy of patients
      with pathohistological verification of small cell carcinoma of the lung with use
      two polychemotherapy regimes (VCAV and CAP) particular or in combination with
      radiotherapy. We achieved the best results with application VCAV regime alone
      (local response 100%, complete response 78.6%, partial response 21.4%) or, in
      combination with radiotherapy in relation on CAP regime. Our results, when
      compared to experiences of foreign authors, though we evaluated it on minority
      series, also demonstrated better results when both regimes of polychemotherapy
      were used.

PMID- 9623076
TI  - [Radiotherapy in the treatment of bronchial carcinoma].
AB  - Aim of this paper is to give the role of the radiotherapy, alone or in
      combination with other treatment modalities, in treatment of lung cancer.
      Conventional external radiotherapy is described, as well as some recent
      techniques: after loading brachytherapy and laser therapy. We concluded that
      radiotherapy has an important role in treatment of lung cancer, mostly as
      palliation, and in some selected cases as a treatment with curative intent.

PMID- 9623077
TI  - [Combined modalities in the treatment of limited small cell lung cancer].
AB  - A combined modalities approach--radiotherapy plus chemotherapy to the treatment
      of limited small cell lung cancer are presented. There are three strategies for
      the treatment: sequential, concurrent and alternative therapy. Concurrent and
      alternative appear to be preferred. Thoracic radiotherapy can be administered
      continuously or "split course". There is a trend favouring the combination of
      Cisplatin + Vepeside as the chemotherapy regimen of choice in combined modality
      therapy for limited small cell lung cancer.

PMID- 9623078
TI  - [Post-radiation fibrosis of the lung].
AB  - The lung fibrosis after irradiation of lung cancer is described in this paper, as
      well as pathologic physiology, clinical signs and symptoms, and radiographic
      changes. Carefully treatment planning using CT scans, simulator and computer
      planning system is the only way to prevent excessive irradiation of the lung and
      correspondent lung fibrosis.

PMID- 9623079
TI  - [Multiple neoplasms].
AB  - This paper describes observation on multiple carcinomas, with emphasis on double
      carcinomas of the lungs and other organs. The paper presents four cases of
      multiple neoplasmas and goes on to discuss eventual etiopathogenesis of multiple
      malignancies. Of the four cases presented in this paper, three cover double
      carcinoma of the throat and lungs, and in the fourth, double carcinoma of the
      lung and bladder. Three of the cases covered relate to metachronous carcinoma and
      the fourth case to synchronous carcinoma.

PMID- 9623080
TI  - [Rehabilitation of patients with respiratory problems--bronchogenic carcinoma].
AB  - Rehabilitation of the patients suffering from the pulmonologic problems with the
      bronchogenic cancer under our circumstances has not, practically, been
      established. There are neither physiotherapy nor kinesiology methods in
      rehabilitation. It would be necessary to appoint a team, consisting of:
      pulmonologist, physiatrist, physiotherapist and nurses with the consultation of
      the service corresponding the needs of the bronchogenic carcinoma problems. Basic
      breathing exercises principles, prior and post operative ones, kinesiotherapy and
      posture drainage techniques were presented in the paper.

PMID- 9623081
TI  - [Psychological and moral problems in physician-patient relations in carcinoma].
AB  - In this article the basic moral and psychological problems a doctor encounters in
      his professional relationship with a cancer patient are being discussed. That
      relationship should be mature one, humanistic and sincere. Unfortunately, in the
      reality it is most frequently an emotionally immature to a certain degree even
      insincere and thus deprived of its humanistic attributes. The reasons for such a
      situation are partly concealed in the very psychological problems a doctor might
      have, which is closely linked to his unconscious motivation for selecting this
      particular profession as his or her walk of life. The aformentioned problems must
      be seen in the light of a wide-spread fallacy that the patient need to be
      preserved from knowing the truth of their doomed state. However, in the same
      time, there is doctrinary attitude that instructs doctors to reveal all the
      details describing the situation realistically to the patient but in sincere,
      thoughtful, warm, humanistic way that can instill some hope to the patient's view
      on his illness. The mechanisms of phychological defense patients uses when faced
      to the truth are also being analysed, as well as all therapeutic preventive
      measures that should have to be taken in addvesing the same issue.

PMID- 9623082
TI  - [Reform of the health care system in Bosnia-Herzegovina].

PMID- 9623083
TI  - [Strategic guidelines for reconstruction and development of health care in the
      Federation of Bosnia-Herzegovina].
AB  - The aim of the study is to represent the strategic outlines of health system
      reconstruction in the Federation of Bosnia and Herzegovina. Considering the
      future health system design we represented the crucial choices of health care
      policy within primary health care, hospital care, public health, health care
      financing, health care of vulnerable groups, as well as reform of medical
      education. A constitutional framework for the organization of health system was
      represented, as well as relevant challenges of transition from socialist system
      to free market economy system.

PMID- 9623084
TI  - [Effect of the war on developmental lag of medical technology in Bosnia
      Herzegovina].
AB  - The war in Bosnia and Herzegovina, caused by the aggression of neighbouring
      countries, besides biological destruction and poverty halted every scientific and
      technological development in all areas, and in medicine, too. This paper presents
      vital events in population, forced migrations and violent deaths also. A
      comparative review and state level of medical technology for particular
      specialist disciplines in B&H is shown for 1995 and 1990. The criteria for the
      assessment of lagging in technology and health development is the number and
      structure of specialized staff, state of premises and medical equipment,
      bioinformatics, etc, with personal estimation of selected number of leading
      experts in various medical disciplines (Delfy method) about working conditions.
      The paper presents the assessment of technological lagging in health sector in
      B&H (average rate of 40.4%) due to the war, related to 1990.

PMID- 9623085
TI  - [Present status of the health care system].
AB  - Characteristic feature of the aggression to BiH are attacks to medical
      facilities, equipment and staff, as well as to the patients in hospitals. All
      international conventions were broken, as well as all elementary human rights.
      Organisation of the work in all medical institutions was spontaneous.
      Nevertheless, continuity and availability of health care delivery was
      satisfactory. Many governmental and non-governmental organizations have helped
      health care system during the war. During the war number of health care
      institutions increased for several reasons: a) founding 86 points of humanitarian
      organizations; b) founding 19 temporary hospitals; c) founding new 14 homes of
      health. Due to war destruction, it is necessary to determine the priorities in
      sanation of certain segments of health care system.

PMID- 9623086
TI  - [Strategic plan for reform and reconstruction of the health care system in the
      Federation of Bosnia-Herzegovina].
AB  - The aim of this study was to represent the document of the Federal Ministry of
      Health entitled "Strategic Plan for Reform and Reconstruction of Health System in
      the Federation of Bosnia and Herzegovina". Strategic outlines of health system
      development in the Federation of B&H during the next three years were represented
      in the document, but in particular within following areas: health care financing,
      primary health care, specialist-consultancy hospital care, public health,
      pharmaceutical issues, health information system, and medical education.

PMID- 9623087
TI  - [Strategic goals in the reform of the health care system in the Federation of
      Bosnia-Herzegovina].
AB  - Reform and transformation of health care system in The Federation of BiH are
      defined by five basic factors: creation of health care system; improvement of
      medical staff; development of infrastructure and basic components; new public
      health program, and mental and physical rehabilitation of ill and invalid
      persons. The basic tenets of new laws on health care system, as well as its
      strategic goals are presented in this paper.

PMID- 9623088
TI  - [Foundation of pharmaceutical policy in the Federation of Bosnia-Herzegovina].
AB  - Pharmaceuticals are inevitable domain of disease prevention, diagnostics and
      treatment. The basic objective of pharmaceutical sector reform is to meet the
      needs of the majority of the population with the essential pharmaceuticals, which
      are proven as effective, evaluated quality and affordable prices. That objective
      could be achieved by undertaking a range of measures within the national
      pharmaceutical policy as an integral part of the overall health, policy in the
      country. Key elements of that policy should be: pharmaceutical management at the
      level of the Federal Ministry of Health and cantonal ministrie of health,
      pharmaceutical legislative documents, rationalization of pharmaceutical therapy
      (choices of essential pharmaceuticals, choices of pharmaceuticals covered by the
      resources of health insurance funds, list of hospital pharmaceuticals, selections
      during pharmaceuticals registration, educational measures, surveillance of
      measures), spreading information on pharmaceuticals by the pharmaceutical
      information centre, pharmaceutical supply (local pharmaceutical production,
      pharmaceuticals import, humanitarian assistance), funding of pharmaceuticals
      costs (cantonal and hospital lists of pharmaceuticals,) other reform strategies
      (quality control of pharmaceuticals, surveillance of side-effects, role of
      pharmacists in health system, environment protection) and strengthening of
      inspector surveillance.

PMID- 9623089
TI  - [Importance of health information systems in the process of reform and
      reconstruction of health care].
AB  - Reform and reconstruction of health care system can not be carried out without
      health information systems and modern information and communication technologies.
      In other hand, health information system of The Federation of BiH must be an
      object of both reform and reconstruction. This thesis points out that reform of
      health information system is a crucial priorities in order to improve and fasten
      reform. There is a paradigmatic question: who provides service, to whom, what is
      the price, and what is the final solution? In order to answer this question, an
      integral health information system that will be computer supported is necessary.
      For integral work and information exchange, computers must be connected and
      follow the same operating procedures. Benefits of an integral health information
      system, as well as impact factors for its implementation are discussed in the
      paper.

PMID- 9623090
TI  - [Essential hospital services].
AB  - The Project of rehabilitation and reconstruction of essential hospital services
      at the overall territory of The Federation BiH till secondary level is briefly
      described in the paper. The Project is carried out with financial assistance of
      IDA and several foreign governments. The Project includes physical reconstruction
      of hospitals, equipment, development of clinical training, reform of health
      financing, and hospital management. 16.25 millions US$ are provided, and 5.25
      millions US$ more is necessary.

PMID- 9623091
TI  - [Organization of health care and health protection in the transitional phase of
      health care reform and under new legal regulations].
AB  - In Federation of Bosnia and Hercegovina, Health Reform is brought up, dictated
      after newly created post-war policy; fundamental laws in health are brought up,
      and changes in constitutional sense, brought the country in the phase of
      transition. Organization of health protection and health business had many
      disadvantages, what impacted its realisation in direction of satisfying needs and
      requirement of the population. This paper-work tries to connect existing
      situation and practice in organization of health care and health business, by
      using relevant rules which were not adequately and completely realised, and were
      without possibility of evaluation. The paper tries, by using new Law regulations
      in Health and Reform to come, to offer organizational solutions which could be
      more acceptable and realisable in this transitional period.

PMID- 9623092
TI  - [Internet in health care--possibilities of use in Bosnia-Herzegovina].

PMID- 9623093
TI  - [Chest pain and electrocardiogram abnormalities: consider pulmonary embolism].
AB  - Pulmonary embolism is a serious and potentially life-threatening disease that
      requires early recognition and treatment. In three patients, two men aged 60 and
      61 and a woman aged 76, prominent severe chest pain and electrocardiographic
      changes suggesting ischaemic heart disease, lack of response to treatment, marked
      dyspnoea and haemodynamic instability eventually led to the clinical suspicion
      and subsequent diagnosis of pulmonary embolism. Electrocardiographic changes are
      indicative of right-sided overload and sometimes of arterial hypoxaemia. Although
      ECG changes are very frequent in cases of pulmonary embolism, the abnormalities
      observed are mostly nonspecific ST-T segment changes.

PMID- 9623094
TI  - [Taxoids in ovarian and breast carcinoma: the role of the medical profession and
      the government].
AB  - After registration in 1993/1995 of paclitaxel and docetaxel for the treatment of
      ovarian and mammary carcinomas, the costliness of these drugs caused Dutch
      hospitals to adopt different policies for their use. This prompted the Minister
      of Health to ask the professional group of oncological internists to draw up a
      guideline for the use of taxoids, following which the government decided to
      supply extra money for the hospitals to use according to this guideline.
      Meanwhile new, contradictory study results have become known, still unpublished
      and in part originating from studies not yet conclude. The pharmaceutical
      industry advocates terminating the current research and maintaining the existing
      indications. However, patients are entitled to unbiased, complete research
      findings. The pathway for introducing new expensive drugs should be as follows:
      the professionals determine the indications for the new drug, the government pays
      attention to the financial consequences. The pharmaceutical industries should
      have no voice in the relevant decision-making.

PMID- 9623096
TI  - [Immunology in medical practice. XIV. Central nervous system complications in
      systemic autoimmune diseases].
AB  - Complications of the central nervous system (CNS) are common in systemic
      autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus
      (SLE) and primary Sjogren's syndrome. Specific diagnostic tests are lacking and
      early intervention with immunosuppressive therapy is frequently necessary.
      Therefore knowledge of these CNS complications is essential for early diagnosis
      and treatment. Residual cognitive effects were observed in some but not in all
      tests after prolonged heavy cannabis use. The effects were mostly mild. The
      relationship of cannabis use, psychotic effects and schizophrenia was unclear;
      the cannabis conceivably gave relief, but it also appeared that cannabis caused
      schizophrenia in young people and (or) enhanced the symptoms, especially in young
      people poorly able to cope with stress or in whom the antipsychotic therapy was
      unsuccessful.

PMID- 9623095
TI  - [Cognitive and psychotic effects after cessation of chronic cannabis use].
AB  - Establishment of residual cognitive and psychotic effects (effects present at the
      time that all active cannabinoids are eliminated from the body) putatively
      produced by prolonged heavy cannabis use is difficult, because of many
      confounding variables like slow elimination of active cannabinoids, lack of
      supervision during abstinence, poor use of well-matched control groups and the
      presence of withdrawal symptoms. Residual cognitive effects were observed in some
      but not in all tests after prolonged heavy cannabis use. The effects were mostly
      mild. The relationship of cannabis use, psychotic effects and schizophrenia was
      unclear; the cannabis conceivably gave relief, but it also appeared that cannabis
      caused schizophrenia in young people and (or) enhanced the symptoms, especially
      in young people poorly able to cope with stress or in whom the antipsychotic
      therapy was unsuccessful.

PMID- 9623097
TI  - [Clinical thinking and decision making in clinical practice. A patient with
      systemic lupus erythematosus and behavioral changes].
AB  - A 48-year-old man with systemic lupus erythematosus (SLE) was admitted with
      fever, headache and mental change. On admission he was treated with daily doses
      of cyclophosphamide 100 mg and prednisone 7.5 mg. Orientation and attention were
      diminished and visual examination revealed right-sided homonymous hemianopia. MRI
      of the brain showed a ring-enhanced, space occupying lesion in the left occipital
      lobe. An infectious disease cause was considered, because disease activity
      parameters of SLE were all negative (anti-dsDNA and the complement profile). The
      anti-Toxoplasma titre was elevated in cerebrospinal fluid (57 IU/ml) and in serum
      (1140 IU/ml), both IgG. A tentative diagnosis of Toxoplasma encephalitis was made
      and a trial anti-toxoplasmosis treatment with pyrimethamine and sulfadiazine was
      administered. Two weeks later the patient was normal at neurological examination
      and his brain MRI had greatly improved. The anti-Toxoplasma titre had dropped
      significantly.

PMID- 9623098
TI  - [Provision of taxoids in 1996: inequality of care].
AB  - OBJECTIVE: To inventory the utilization of taxoids in 1996. METHODS: A survey was
      conducted in february 1997 among the medical heads of 130 Dutch hospitals. The
      questions about the use of taxoids (paclitaxel and docetaxel) in 1996 concerned
      indications, numbers of patients treated, the funding and possible financial
      restrictions on the treatment. Three weeks after the mailing of the
      questionnaire, a reminder was sent to hospitals that had not responded. The data
      from 120 hospitals where oncological care was administered were analysed.
      RESULTS: Of the 120 hospitals, 111 (92.5%) returned the questionnaire, from 114
      locations. Twelve locations reported not having used taxoids, four of them partly
      for financial reasons. Taxoids had been used at 102 locations: at the expense of
      the hospital budget at 101 locations, and exclusively at the expense of sickness
      insurers at one location. At 27 locations, paclitaxel and docetaxel had also been
      issued in the context of trials, and at 7 locations also via special agreements
      with the insurers and (or) at the expense of the patient himself. Fifty-three of
      the 102 taxoid using hospitals had a financial upper limit or a maximum number of
      patients to be treated. Eighteen of the 102 locations where paclitaxel or
      docetaxel was issued reported that for financial reasons not all patients
      eligible for taxoids had been given these drugs. The indications varied from one
      hospital to another: 67 locations used them for first-phase treatment of patients
      with ovarian carcinoma, 96 locations for second-phase treatment of patients with
      ovarian carcinoma and at 91 locations, patients with mammary carcinoma were given
      taxoids when anthracyclines were no longer indicated. CONCLUSION: Hospitals in
      1996 varied greatly with regard to issuing of taxoids. This diversity in part had
      financial causes. Restrictions on the issuing of taxoids for financial reasons
      lead to unequal access to care.

PMID- 9623099
TI  - [Hepatitis A epidemic in Heerlen in late 1996, importance of immunization in
      immigrant children].
AB  - OBJECTIVE: Description of a local epidemic of hepatitis A in 1996 in Heerlen, the
      Netherlands. DESIGN: Descriptive. SETTING: Regional Health Service Oostelijk Zuid
      Limburg, Heerlen, the Netherlands. METHOD: Semistructured questions were asked by
      telephone of patients, patients' parents, general practitioners, the day-care
      centre manager and the head of the primary school, to collect information about
      cases. RESULTS: In the last four months of 1996, 41 persons (23 children and 18
      adolescents and adults) were infected in a city of some 50,000 inhabitants. The
      primary case was most likely a three-year-old boy from Moroccan parents, who
      prior to his disease had visited his family in Morocco and although non-immune
      had not been immunised. From the boy's family the virus spread to a day-care
      centre and a primary school. In this epidemic patients of 15 different general
      practitioners were affected. An intervention with hepatitis A immunoglobulin in
      the day-care centre and primary school and immunoglobulin prophylaxis in affected
      families was effective in halting the epidemic. CONCLUSION: Special attention is
      needed for immunisation of children of travelling immigrant parents.
      Immunoglobulin prophylaxis in affected families and notification of cases to the
      regional health institute by general practitioners may prevent cases. Serological
      notification by the regional laboratory as well as notification of infectious
      diseases by day-care centres and schools will add to the regional infection
      surveillance and control.

PMID- 9623100
TI  - [Fixation of facial and auricular prosthesis with osseous implants in cranial
      bone].
AB  - OBJECTIVE: To evaluate the use of osseointegrated implants to fix facial and
      auricular prostheses. DESIGN: Retrospective. SETTING: University Hospital
      Groningen, the Netherlands. METHODS: Thirty patients were treated with Branemark
      implants for fixation of auricular (21 patients) and orbital (9 patients)
      prostheses during May 1988-December 1995. The complications during the procedure,
      the success rate of the implants, skin reactions around the implants and patient
      satisfaction were recorded. RESULTS: A total of 97 implants were placed. One
      implant had to be removed after the healing period because it was loose. No other
      implants were lost during the follow-up period (mean 36 months; range: 12-91).
      The skin around the implants sometimes showed a mild reaction which could be
      adequately treated. In most of the cases no inflammation of the skin was
      observed. Retention, ease of handling and wearing comfort of the facial
      prostheses were excellent. CONCLUSION: Fixation of facial and auricular
      prostheses can be improved by osseointegrated implants resulting in high patient
      satisfaction.

PMID- 9623101
TI  - [Botulinum toxin type A treatment of cosmetically disturbing masseteric
      hypertrophy].
AB  - Two patients, a woman aged 21 and a man aged 29, with asymmetrical swellings of
      both mandibular angles and a painful, heavy sensation in the masticatory muscles
      (and in the woman also round the maxillary joint), were diagnosed as having
      hypertrophy of the masseter muscles. Both had the habit of jaw clenching and
      tooth grinding. Treatment consisted not of the traditional surgical debulking
      which also allows correction of overdeveloped osseous mandibular angles, but of
      injections with botulinum toxin type A. Injection of 40-60 IU (product: Botox)
      per muscle was followed by some atrophy; cosmetically satisfactory results were
      achieved after repetition of the treatment a few months later. Reduction of
      muscle volume was confirmed by a quantitative volumetric assessment of MRI scans.
      In the female patient, the pain also abated.

PMID- 9623102
TI  - [Kimura's disease].
AB  - An Asian man aged 42 had a pre-auricular swelling on the left with local skin
      itching. Owing to the highly probably benign nature at examination, surgical
      treatment was refrained from. One year later, the swelling had increased while
      the itching was unchanged, so that surgical excision was performed. Morbid
      anatomical examination revealed angiolymphoid hyperplasia with eosinophilia,
      compatible with Kimura's disease. Kimura's disease is a chronic inflammatory
      disorder which is very rare in Europe, but which is frequently diagnosed in Asian
      countries and in immigrants from these countries. Tumours in the head and neck
      region, enlarged lymph nodes and increased eosinophil counts are typical signs.
      The IgE level is increased. The cause of this disease is so far not clear,
      although there are indications that an inflammatory reaction to an unknown
      allergen plays a part. It is essential that this disease should be distinguished
      in the diagnostic work-up from presence of a malignancy. Fine-needle aspiration
      cytology is often inconclusive; as a rule the diagnosis can only be made after
      surgical excision of the tumour. There is no consensus on the treatment of this
      disease, but symptomatic therapy usually suffices.

PMID- 9623103
TI  - [Prevalence of different lipid concentrations in Curacao].

PMID- 9623104
TI  - [Myocardial tissue vitality: clinical relevance, pathophysiology nd
      identification].

PMID- 9623105
TI  - [Assisted suicide in psychiatry in the Netherlands].

PMID- 9623106
TI  - [Psychiatric morbidity of adults in the Netherlands: the NEMESIS study].

PMID- 9623107
TI  - [Inventory follow-up of patients operated on for utero-vaginal prolapse and no
      longer affected by stress incontinence].

PMID- 9623108
TI  - [Lichen sclerosus et atrophicus as the cause of genital abnormality in a girl].

PMID- 9623109
TI  - [Iatrogenic stress pneumothorax after a wrongly placed stomach tube].

PMID- 9623110
TI  - ['Inclusion body'-myositis].
AB  - In 3 patients, a 72-year-old man, a 62-year-old man and a 73-year-old woman with
      weakness of respectively the quadriceps femoris, the finger flexors and the
      pharyngeal muscles, the diagnosis of 'inclusion body myositis' was made. This is
      a rare, slowly progressive skeletal muscle disorder which is more common in men
      and after the age of fifty. The activity of serum creatine kinase is often 2-5
      times the highest normal value. The electromyogram pattern is myopathic, but can
      also display neuropathic changes (exclusively). Inclusion body myositis is often
      misdiagnosed, which can lead to an inappropriate treatment or approach. A frozen
      muscle biopsy is needed to make cryostat sections for demonstration of myositis
      with rimmed vacuoles.

PMID- 9623111
TI  - [Feeding tubes for tube feeding].
AB  - Several techniques are available for the provision of enteral nutritional
      support. Nasal tubes, gastrostomy tubes and jejunostomy tubes can be
      distinguised. Nasal tubes are used for short-term support, gastrostomy tubes
      (preferably via a percutaneous endoscopic gastrostomy) for long-term support
      (over 4 to 6 weeks), while (needle catheter) jejunostomy tubes are most often
      used to provide early enteral nutrition immediately after operations on the
      proximal gastrointestinal tract. The most frequent complications are: with the
      nasal tube dislodging, clogging and aspiration, with the gastrostomy tube
      peristomal infection and with the jejunostomy tube, obstruction. It should
      further be noted that the quantity of enteral nutrition prescribed and that
      actually administered may differ substantially so that patients with a feeding
      device may even become malnourished. With proper patient selection and secure
      control of the energy balance, feeding tubes are simple (temporary) devices that
      improve the patient's health and quality of life.

PMID- 9623112
TI  - [Asthma and pregnancy].
AB  - Pregnancy is accompanied by physiological hyperventilation that may be perceived
      as shortness of breath; causes are a reduced residual capacity and a reduced
      expiratory reserve volume due to the swelling uterus, and a larger tidal volume
      due to increase of the progesterone concentration and of the chemosensitivity to
      CO2 and O2. Fatigue, lowered exercise tolerance and orthopnoea also may occur, as
      do basal crepitations at auscultation. In pregnant asthma patients the symptoms
      may either improve greatly or become aggravated. During an asthma attack the
      foetus is exposed to hypoxaemia, which may be worsened by a decreased
      uteroplacental blood circulation in case of maternal alkalosis. Poorly controlled
      asthma has a stronger adverse effect on the unborn child than the judicious use
      of anti-asthma drugs. Safe drugs against asthma during pregnancy, around
      parturition and during breast feeding, are cromoglycic acid and ipratropium;
      relatively safe drugs are short-acting beta-sympathicomimetics, inhalation
      corticosteroids and systemic corticosteroids, as well as theophylline from the
      second trimester; use of long-acting beta-sympathicomimetics is advised against.

PMID- 9623113
TI  - [AIDS; new developments. V. The role of chemokines and chemokine receptors during
      infection with HIV].
AB  - Chemokine receptors appear to be essential coreceptors (next to the CD4 receptor)
      for viral entry of HIV. Non syncytium inducing (NSI) HIV variants
      (monocytotropic) use the beta-chemokine receptor CCR5, syncytium inducing (SI)
      variants (lymphocytotropic) the alpha-chemokine receptor CXCR4. Mutations in CCR5
      appear to give protection against HIV infection and to slow disease progression.
      Blocking of chemokine receptors interrupts HIV infection in vitro and offers new
      options for therapeutic strategies. Theoretical progress has been made in the
      development of an animal model for HIV infection owing to the elucidation of the
      role of chemokine receptors in HIV entry into the cell. In the future HIV
      variants will be classified according to their interaction with chemokine
      receptors.

PMID- 9623114
TI  - [Virological evaluation of treating HIV-infected patients with (combinations of)
      antiretroviral drugs at the Amsterdam Academic Medical Center, 1996/'97].
AB  - OBJECTIVE: First clinical virological evaluation of anti-HIV treatment with HIV
      reverse transcriptase (RT) and protease inhibitors. DESIGN: Descriptive. SETTING:
      Academic Medical Centre of the University of Amsterdam, the Netherlands. METHOD:
      From January 1, 1996, until May 1, 1997, HIV-RNA levels were determined in
      sequential serum or plasma samples obtained sequentially of 384 patients over a
      period of 3.1 years on average (minimum 0.5, maximum 10 years). Of these patients
      318 had sustained treatment for at least 6 months. The effect on HIV-RNA serum or
      plasma levels was evaluated in this particular group, of which 224 (70.4%) had
      been pretreated with antiretroviral drugs (experienced patients) and 94 (29.6%)
      had not (naive patients). RESULTS: Of the naive patients 8.5% were treated with a
      combination of two, 89.4% with three and 2.1% with four anti-HIV drugs. Preceding
      their current treatment, an average of more than two other anti-HIV regimens had
      been administered to the experienced patients. From 1987 until May 1997 a total
      of 834 treatments were registered among the 224 patients: 202 mono, 223 double,
      340 triple, 60 quadruple and 9 other combination treatments. After six months 84%
      of the triple combination treatments in the naive patients and 61% in the
      experienced patients resulted in RNA levels < or = 10(3) copies/ml (p = 0.008).
      Of 68 patients who failed on treatment 36 (52.9%) showed resistance associated
      mutations in HIV reverse transcriptase. In 6/43 (14%) of these patients
      resistance associated mutations in protease were found as well. Genotypic
      resistance could not always be confirmed phenotypically. CONCLUSION: Our
      preliminary results indicate that in a majority of cases triple combination
      treatment including at least one HIV protease inhibitor was successful.
      Nevertheless, in 16% of the therapy-naive and 39% of the therapy-experienced
      patients the anti-HIV effect of treatment was insufficient.

PMID- 9623115
TI  - [Preoperative diagnosis with stereotactic biopsy is a good predictor of breast
      cancer in radiologically non-benign breast lesions].
AB  - OBJECTIVE: To evaluate histological needle biopsy in breast lesions classified
      radiologically as 'non-benign'. DESIGN: Prospective, descriptive. SETTING:
      Hospital Velp, Velp, the Netherlands. METHODS: 232 women with an 'uncertain',
      'suspicious' or 'malignant' result of mammography, if necessary supplemented by
      echography, were subjected to histological biopsy from a breast between 1 January
      1994 and 1 January 1997. The earlier biopsies were made with a 16 Gauge (G)
      needle, those after April 1996 with a 14 G needle, as a rule under stereotactic
      control. In principle, operation was performed after a positive result.
      Concerning the women operated after the biopsy, the results of the histological
      examinations were compared in a 2 x 2 table. RESULTS: 165 of the 232 patients
      (71%) had breast cancer. Of the 59 patients classified roentgenologically as
      'uncertain', 15 (25%) had breast cancer, of the 'suspicious' cases this ratio was
      44/67 (66%) and of the 'malignant' results it was 106/106 (100%). Operation was
      performed in 186 women. The biopsy findings and the surgical preparation were in
      agreement in 169 patients (91%). The sensitivity of the stereotactic biopsy was
      90%, its specificity 93%. One woman was over-treated (axillary lymph node
      resection) because of a biopsy classified as malignant performed on a rare tumour
      ultimately diagnosed as 'adenomyo-epithelioma with epithelial atypia'. The
      proportion of false-negative results was 36%. The predictive value of a positive
      result was 99%, that of a negative result 63%. CONCLUSION: A diagnostic
      stereotactic biopsy after roentgenological classification based on mammography
      and echography had a good predictive value regarding the probability of breast
      cancer.

PMID- 9623116
TI  - [Gentamicin administration in newborns: once daily].
AB  - OBJECTIVE: To determine the serum levels of gentamicin in newborn on one or two
      daily doses. DESIGN: Retrospective and subsequently prospective, descriptive.
      SETTING: Department of Pediatrics of the Deventer Hospital, the Netherlands.
      METHOD: Gentamicin trough and peak plasma levels were analysed retrospectively in
      30 neonates to whom gentamicin 3-4 mg/kg/day in two doses had been administered
      in 1995. In a subsequent prospective study in 1996, 52 neonates received
      gentamicin 4 mg/kg/day in one dose. Optimal levels were defined as a trough of <
      2 mg/l and a peak of 6-12 mg/l. Levels were determined using a immunoassay.
      RESULTS: Both groups were similar in gestational age, weight and age at the start
      of treatment. Both trough and peak plasma levels were not known in all patients.
      Adequate gentamicin trough levels were seen more often in the 'once daily' group
      than in the 'twice daily' group, in both the premature (12/14 = 86% versus 3/7 =
      43%; p = 0.04) and non-premature (36/37 = 97% versus 18/23 = 78%; p = 0.017)
      neonates. Peak levels were higher in the 'once daily' group than in the 'twice
      daily' group, in both the prematures (11/13 = 85% versus 1/7 = 14%; p = 0.002)
      and non-prematures (25/28 = 89% versus 2/22 = 9%; p < 0.000001). Optimal trough
      and peak levels were found in 9/13 (69%) of the premature and 24/27 (89%) of the
      non-premature neonates treated according to the 'once daily' schedule, compared
      with 0 and 1/22 (5%) respectively in the neonates treated according to the 'twice
      daily' regimen (p = 0.003 and p < 0.0001, respectively). CONCLUSION: In view of
      the reported levels and the literature, an initial dose of gentamicin of 4.0
      mg/kg/day once a day is advised for neonates.

PMID- 9623117
TI  - [Invasive infection with Haemophilus influenzae type b in spite of complete
      vaccination].
AB  - Five patients, 4 boys and 1 girl aged 13-41 months, developed invasive
      Haemophilus influenzae type b (Hib) disease (2 epiglottitis, 3 meningitis)
      despite full (or at least 3 times) vaccination. At admission as well during
      convalescence, 3 out of 5 had IgG anti Hib antibody levels < or = 5 U/ml. Serum
      immunoglobulin levels, including IgG subclasses, as well as complement were
      normal in all cases. In 2 of the 3, booster vaccinations with Hib conjugate
      vaccine elicited adequate antibody titres. Since the incorporation of the
      conjugated Hib polysaccharide tetanus toxoid vaccine (HibTT) in the National
      Vaccination Programme in the Netherlands, the number of invasive infections
      caused by Hib has dropped significantly. Causes of Hib conjugate vaccine failures
      are mostly unknown. In about one-third of the cases serum immunoglobulin levels
      are deficient, most often IgG2 or IgM. Susceptibility to Hib infection is in part
      also genetically determined. In the follow-up of Hib vaccine failures, anti Hib
      antibody titres should be determined. Booster vaccinations may be necessary.

PMID- 9623118
TI  - [Neuropsychiatric adverse effects attributed to use of oxybutynin].
AB  - Since 1988, the Netherlands Pharmacovigilance Foundation Lareb and the
      Inspectorate for Health Care have received 17 reports of patients with
      neuropsychiatric adverse reactions attributed to the use of oxybutynin
      hydrochloride. These concerned 6 males and 11 females and 6 out of the 17
      patients were children under the age of 13. In all cases patients had been
      treated according to a normal dosage regimen. Complaints included hallucinations,
      psychosis, concentration and orientation problems, apathy, listlessness,
      agitation, drowsiness and sleepiness. Symptoms improved or disappeared in all
      patients after dose reduction or withdrawal of oxybutynin.

PMID- 9623119
TI  - [Worldwide care of people with HIV-infection or AIDS; report of an international
      conference held in Amsterdam].
AB  - Millions of people all over the world are HIV-infected; 90% of them are living in
      developing countries. Other heavily affected groups are homosexual males, drug
      addicts, workers in the sex industry and other fringe groups. Taking suitable
      care of these patients and their families is a major task. This was the subject
      of the third international conference on home and community care in HIV
      infection/aids, held in Amsterdam in May 1997. There is a world of difference
      between the rich West and developing countries in regard to number of patients
      and availability and accessibility of care. Moreover, in developing countries the
      inferior socioeconomic position of women and children substantially impairs
      effective care programmes. Drugs against HIV and against opportunistic
      infections, and means of palliative care are not available and not affordable in
      these countries. Local initiatives to improve this situation can only succeed
      given an infrastructure for the care that is supported by the authorities, so
      that continuity is guaranteed. Structural cooperation between these authorities
      and international bodies, and large-scale support by Western foreign aid services
      are indispensable.

PMID- 9623120
TI  - [Ovum fertilization with surgically implanted sperm: extra risk for each
      offspring is unlikely with careful practice].

PMID- 9623121
TI  - [Vulvar dynamics a a cause of vulvar vesitubulitis syndrome].

PMID- 9623122
TI  - [Frequency of postoperative wound infections in the Netherlands].

PMID- 9623123
TI  - [Psychiatric disorders in refugees and asylum seekers: psychological trauma as a
      cause?].
AB  - Posttraumatic stress disorder was diagnosed in two patients, men aged 26 and 29,
      an asylum seeker from the Middle East and a refugee from former Yugoslavia
      respectively. They had experienced severe psychotraumatic events. They were
      referred to a clinic for traumatised refugees and asylum seekers. Their
      psychiatric disturbances did not fit posttraumatic stress disorder, however. The
      former suffered from a schizophrenic disorder, the latter from psychosis and
      depression based on alcohol dependence. Growing awareness of the high prevalence
      of traumatic experiences in the population leads to a contextual shift in
      therapists regarding their understanding of the short and long term effects of
      traumatization in their patients. Exclusive focus on the traumatic history,
      however, biases the diagnostic process and could lead to wrong conclusions about
      a causal relationship between traumatic experiences and the psychopathology
      observed in the patient. When treating asylum seekers or refugees the risk of
      jumping to this false conclusion is even higher, partially due to cultural and
      language barriers.

PMID- 9623124
TI  - [Adverse effects of sunlight on the skin].
AB  - Many people consider a summer's day pleasant: warm and bright. The sun's
      ultraviolet rays do not contribute to the pleasure, and are biologically mainly
      harmful. As UV radiation does not penetrate any deeper than our skin, this organ
      has to be particularly well adapted to the UV exposure. The skin exploits the UV
      radiation for the synthesis of vitamin D3. Our day-to-day exposure suffices for
      this beneficial UV effect. Excessive exposure, as in sunbathing, only contributes
      to the adverse effects, like sunburn and suppression of cellular immunity in the
      short term, and 'photoaging' and skin cancer in the long term. The UVB radiation
      in sunlight is mainly responsible for these harmful effects, the UVA radiation to
      a far lesser extent (10-20% contribution). The UVA radiation from modern tanning
      equipment does not differ from that in sunlight, but UVA radiation does not lead
      to vitamin D3 production; it rather degrades vitamin D3 and a tan offers
      insufficient protection against the UVB radiation in full sunlight.

PMID- 9623125
TI  - [No strong evidence of disturbed regulation of blood pressure in chronic fatigue
      syndrome].
AB  - Recent medical publications postulate a connection between the Chronic Fatigue
      Syndrome (CFS) and disturbed regulation of the circulation, manifesting itself
      during orthostatic stress testing. Four studies were published on the circulatory
      response on prolonged head up tilt testing. Numerous CFS patients displayed
      postural tachycardia or syncope during the test. However, many CFS patients
      examined had had orthostatic symptoms prior to the examination. It is not certain
      that cardiovascular dysregulation is present in CFS patients without orthostatic
      symptoms. It is also not clear whether such a dysregulation would be the effect
      of physical inactivity or a manifestation of a subtle form of autonomic
      neuropathy.

PMID- 9623126
TI  - [Pain in the breasts].
AB  - Many women occasionally suffer from periods of sometimes severe breast pain.
      Little is known about the aetiology. Although breast pain is rarely a symptom of
      breast cancer, the primary aim of examination is to exclude this diagnosis. For
      most women reassurance with respect to breast cancer appears to be adequate
      treatment. If the pain persists or is so severe that it interferes with normal
      life, drug treatment should be considered after exclusion of the possibility of
      breast cancer. Surgical treatment of diffuse breast pain should be discouraged.

PMID- 9623127
TI  - [Pharmacotherapeutic compass 1998].
AB  - The Central Medical Pharmaceutical Committee of the Health Insurance Council
      informs the medical profession annually about the effects of drugs through the
      Pharmacotherapeutical Compass. The 1998 edition now contains a chapter on
      pharmacokinetics as well. Compared with previous editions the main alterations of
      the contents concern an introduction and advice on the antidepressants, two
      protocols with respect to the medical treatment of patients suffering from
      epilepsy, advice with respect to oral drugs for the treatment of inflammatory
      bowel disease, an introduction and advice regarding the treatment of allergic
      rhinitis, the treatment of patients suffering from AIDS with antiretroviral
      drugs, the treatment of genital herpes, the taking of insulin lispro by patients
      with diabetes and the taking of bisphosphonates to prevent or to treat
      osteoporosis. Two corrections to the 1998 edition are given.

PMID- 9623128
TI  - [Impairment and disability in patients with a severe ischemic cerebral infarction
      at admission to the rehabilitation center and six months after stroke].
AB  - OBJECTIVE: Evaluation of impairment and disability in stroke patients with a
      severe cortical infarction at admission as well as six months after the stroke.
      DESIGN: Prospective and descriptive study. SETTING: Rehabilitation Centre
      Heliomare, Wijk aan Zee, the Netherlands. METHODS: Between 1 January 1987 en 31
      May 1992 stroke patients were admitted to the rehabilitation centre with a
      severe, first ever, cortical infarction without any comorbidity. The patients
      were dependent in activities of daily living and wheel-chair-bound. Motor and
      neuropsychological impairment and disability were evaluated at admission to the
      rehabilitation centre as well as six months after the stroke. Return to home and
      length of stay were evaluated. RESULTS: 43 patients were included. Recovery of
      arm and hand function was very poor (there was complete paresis at admission in
      33 patients (77%) and six months after the CVA in 25 patients (58%)); recovery of
      the affected leg was reasonable (complete paresis in 10 (23%) and 0 patients,
      respectively). Cognitive deficits diminished in severity, but remained noticeable
      in three-quarters of the patients. Independent walking was achieved by 30
      patients (70%), independence in personal activities of daily living by 32
      patients (74%) and returning home by 36 patients (84%). The mean hospital stay
      was 26 weeks (SD: 9.26; range: 11-30). CONCLUSION: Prognosis of personal
      independence and returning home after a severe cortical infarction was rather
      good despite poor recovery of motor and cognitive impairment.

PMID- 9623129
TI  - [Improved prognosis of functional abdominal complaints by attending to psychic
      factors].
AB  - OBJECTIVE: To determine the assessment by physicians of psychic factors in
      patients with functional abdominal complaints, and the relationship between the
      assessment and the evolution of the abdominal complaints. DESIGN: Prospective,
      descriptive. SETTING: Outpatient Clinic Internal Medicine, University Hospital
      Nijmegen, the Netherlands. METHODS: 120 patients with functional abdominal
      complaints were asked to indicate by questionnaires the severity and meaning of
      their complaints prior to and at the end of the visits to their internist.
      Internists were asked how they rated the somatic and non-somatic complaint
      dimensions in their patients. RESULTS: Overall, internists perceived the severity
      and details of the abdominal complaints correctly. Prognostically unfavourable
      complaint-related cognitions and emotions were perceived less correctly. During
      the outpatient consulting period, patients' anxiety and somatic attributions
      diminished, especially when the internist had perceived these aspects correctly.
      Six months after the first outpatient visit the abdominal complaints of these
      reassured patients had improved, compared with patients with persistent somatic
      attributions; the latter made more frequent use of health care services at follow
      up (GP visits, drug use). CONCLUSION: Systematic exploration of somatic and non
      somatic complaint dimensions by physicians could be an important tool in
      improving the prognosis and diminishing the medical consumption in patients with
      functional abdominal complaints.

PMID- 9623130
TI  - [Determination of one national standard for children with congenital anomalies in
      the National Obstetrical Registry and in the National Neonatal Registry].
AB  - OBJECTIVE: To determine if the birth prevalence data on congenital malformations
      in the national perinatal registries, the Landelijke Verloskunde Registratie
      (LVR) (National Obstetrical Registry) and the Landelijke Neonatologie Registratie
      (LNR) (National Neonatological Registry), can be combined into one nationwide
      database, and if so to determine the validity of this database. DESIGN:
      Descriptive. SETTING: TNO Prevention and Health, Leiden, the Netherlands.
      METHODS: Investigation of the registered number of congenital malformations in
      the LVR/LNR, the amount of overlapping and the possibility of combining the LVR
      and LNR into one nationwide database. The validity of this database was evaluated
      by comparing the total number of registered children with the total number
      expected in the Netherlands. Furthermore the total number of children registered
      in the nationwide database was compared with children registered by the European
      registration of congenital anomalies and twins (EUROCAT) in the Northern
      Netherlands. RESULTS: The LVR and LNR were mostly complementary with respect to
      the registration of congenital anomalies and could be combined to one nationwide
      database. For sixteen important diagnoses this nationwide database contained
      approximately 87% of the total number expected in the Netherlands. Comparing this
      database with the data of EUROCAT in the Northern Netherlands showed that one
      third of these congenital malformations (n = 229 in 217 children) were registered
      in both systems, while 99 (43%) were only registered by EUROCAT and 50 (22%) only
      by the nationwide database. CONCLUSION: It was possible to create a nationwide
      database, which can supplement the regional EUROCAT data with nationwide data on
      sixteen important diagnoses of congenital malformations.

PMID- 9623131
TI  - [Meningo-encephalitis and hydrocephalus caused by Epstein-Barr virus].
AB  - In a 35-year-old woman who presented with acute somnolence, confusion and slow
      irregular breathing, Epstein-Barr virus (EBV) meningoencephalitis was diagnosed
      after serological testing and a polymerase chain reaction of the cerebrospinal
      fluid. She developed papilloedema and bilateral nervus abducens paresis. A CT
      scan showed generalized oedema of the brain and triventricular hydrocephalus.
      Treatment with a ventriculoperitoneal shunt and ganciclovir led to complete
      recovery. Meningoencephalitis is a not uncommon, yet rarely reported complication
      of infectious mononucleosis. It usually runs a mild course with spontaneous and
      full recovery. Hydrocephalus secondary to aqueduct stenosis is a complication of
      Epstein-Barr virus (EBV) meningoencephalitis which has not been reported in
      adults before. The disease should be considered whenever the clinical condition
      deteriorates or neurological symptoms increase.

PMID- 9623132
TI  - [Fatal varicella-zoster encephalitis; a rare complication of herpes zoster].
AB  - In a 82-year-old woman varicella zoster encephalitis was diagnosed, a rare
      complication of shingles. The case was remarkable for its rapid and fatal course
      in a patient without an underlying disease. At autopsy, the histological picture
      of an acute haemorrhagic encephalitis was seen, also a rare finding.

PMID- 9623133
TI  - [Lead in drinking water: a risk to bottle-fed infants; a Health Council report].
AB  - On April 28th, 1997, the Health Council of the Netherlands Committee on Lead in
      Drinking Water presented their advisory report to the Minister of Housing,
      Spatial Planning and the Environment and the Minister of Health, Welfare and
      Sport. In the report the Committee concluded that, through intake of drinking
      water, small infants are at risk of being exposed to concentrations of lead that
      can be detrimental to health, viz., infants in the first six months of life who
      are bottle-fed on formula milk made up using water that has passed through lead
      piping. In order to protect this specific group, the Committee advised to lower
      the currently effective standard for lead in drinking water from 50 to 10
      micrograms/l and to replace all lead piping as soon as possible.

PMID- 9623134
TI  - [How can the family physician make a mistake?].

PMID- 9623135
TI  - [Lactational amenorrhoea as a birth control method].

PMID- 9623137
TI  - [Ocular paresis and confusion].

PMID- 9623136
TI  - [Lactational amenorrhea as a birth control method].

PMID- 9623138
TI  - [What is the meaning of the concept "incapacity for work"?].
AB  - In the Dutch Social Disability Insurance Act (WAO) the unit of measure is the
      loss of wages the client sustains due to his handicap, not the disease, illness
      or handicap itself. In principle disability is not established by medical facts
      only: the main question is what a client could earn by working fulltime in
      suitable work. For that reason it is usually the labour expert, not the doctor
      who ultimately assesses the measure of disability. In spite of health complaints,
      everyone can still do something and disability on pure medical grounds therefore
      is, or at least should be, rather exceptional. The WAO gives no compensation for
      injury, grief, or overtaxed private conditions. A client does not have to confine
      himself to the jobs mentioned in the judgement by the labour expert.

PMID- 9623139
TI  - [Effectiveness of manipulative therapy in low back pain: systematic literature
      reviews and guidelines are inconclusive].
AB  - In the Dutch general practitioners' guidelines spinal manipulative therapy (SMT)
      is not recommended for treatment of acute low back pain. This is in contrast to
      the recent American and English guidelines, which explicitly recommend SMT for
      this indication. Randomized clinical trials (RCTs) on SMT are on average of low
      methodological quality. Most systematic reviews, however, lead to positive
      conclusions. The potential sources of discrepancy between the recommendations in
      the national guidelines are: interpretation of the available RCTs and systematic
      reviews, composition of the guideline-setting committee, values of the
      participants and appreciation of direct and indirect costs. Definite conclusions
      on the efficacy of SMT for (acute) low back pain cannot yet be drawn. Therefore,
      more RCTs in various settings and on different indications are clearly needed.

PMID- 9623140
TI  - [The pathophysiology and treatment of cholestatic pruritus].
AB  - Pruritus is a frequent, distressing and sometimes disabling symptom of liver and
      biliary tract disorders. Results of treatment are sometimes disappointing and the
      pathophysiology is still largely unknown. It was recently discovered that
      endogenous opioids contribute to the perception of itching and that opiate
      receptor antagonists can reduce the overstimulation of these receptors and
      thereby attenuate the itching. A stepwise treatment strategy focusing
      successively on ion exchange resins, rifampicin and opiate receptor antagonists
      leads to effective alleviation of itching in most patients.

PMID- 9623141
TI  - [Hormonal therapy of constitutionally tall children].
AB  - Children of constitutionally tall stature may experience serious problems related
      to their height. Treatment with high dose sex steroids may be considered in order
      to limit final adult height. Prediction of adult height plays a central part in
      the management of children of tall stature. Various aspects of height prediction
      in children of tall stature are discussed. The height reducing effect varies
      between studies from 2 to 10 cm. Recently, in a large Dutch study the mean
      effects of therapy were 0.7 and 2.4 cm for boys and girls respectively. The
      effect depended on the bone age at start of treatment. Beyond a critical bone age
      of about 14 years treatment had no effect. Minimal age for intervention is 9.5-10
      year for boys and 9.0-9.5 year for girls. Recommended treatment for boys is 250
      mg testosterone esters i.m. per week and for girls ethinyloestradiol orally 200
      micrograms per day in combination with medroxyprogesterone or dydrogesterone
      (both 5-10 mg per day) during the first 12-14 days of the cycle. Treatment has to
      be continued until complete closure of the epiphyses. While side effects during
      hormonal therapy are frequent, they are mostly temporary and mild and seldom lead
      to cessation of therapy. So far there have been no indications of adverse effects
      on, for instance, gonadal function.

PMID- 9623142
TI  - [Evaluation of drugs: efficacy, applicability, effectiveness and efficiency].
AB  - In view of rising costs of drugs and the limited budget, government, institutes,
      researchers, prescribers, pharmacists and pharmaceutical industries should have a
      standardized assessment system at their disposal on which to base their
      pharmacotherapeutic policy. Evaluation can be achieved in four successive steps,
      taking into account both therapeutical and financial aspects. The first two
      steps, determining efficacy and applicability, represent the current system of
      evaluating drugs before allowance to the market. Steps 3 and 4 describe the ways
      in which effectiveness and efficiency can be involved in the evaluation by means
      of (cost) effectiveness analysis. Achieving optimal results from this stepwise
      approach requires speedy acceptance of the currently available guidelines for
      effective and efficient research.

PMID- 9623143
TI  - [Perioperative mortality and the role of anesthesiologic activity at the Vrije
      University Hospital in Amsterdam].
AB  - OBJECTIVE: To determine the perioperative mortality and the share of
      anaesthesiological activity in it. DESIGN: Retrospective, descriptive. SETTING:
      VU University Hospital, Amsterdam. METHOD: Patients who in the period 1989-1994
      had died within 7 days after a clinical surgical intervention were identified
      using the database of the hospital information system. The following data
      concerning these patients were collected from the database of the department of
      Anaesthesiology: age, sex, classification according to the American Society of
      Anesthesiologists (ASA), urgency (elective or emergency operation), type of
      operation (12 categories), duration of the operation, time and place of death.
      Four independent investigators classified the deceased patients with the aid of
      their medical files as to the degree of connection between the anaesthesiological
      activity and the death according to the Edwards classification. RESULTS: A total
      of 62,969 operations had been performed. following which 314 patients (0.5%) had
      died within 7 days. Death was connected with the anaesthesiological activity in
      16 cases (2.5 per 10,000 operations): there was a connection with the
      anaesthesiological activity exclusively in two patients (0.3 per 10,000
      operations) and with both anaesthesiological and surgical factors in 14 patients
      (2.2 per 10,000 operations). Advanced age, male sex, a higher ASA category,
      traumatological operations and emergency operations were associated with a higher
      mortality rate. CONCLUSION: The mortality rate within 7 days after a clinical
      surgical intervention was 0.5%. A connection with anaesthesiological activity was
      present in 2.5 per 10,000 operations.

PMID- 9623144
TI  - [Preconception screening of parents and carrier state of cystic fibrosis in the
      Netherlands: expenses and savings].
AB  - OBJECTIVE: To evaluate effects, costs and savings for a preconceptional couple
      screening programme for cystic fibrosis (CF) carriers. SETTING: State University
      Groningen, the Netherlands. DESIGN: Prospective theoretical evaluation. METHOD: A
      decision tree and an arithmetic model were constructed for two different
      strategies of preconceptional CF screening of couples: 'single entry two step'
      (SETS; start by testing one partner), and 'double entry two step' (DETS; test
      both partners). The difference between costs of screening and costs of CF illness
      prevented by screening was determined. RESULTS: DETS couple screening with the
      assumptions used for e.g. sensitivity and use of options can detect 81.5% of
      carrier couples in the Netherlands (against 70% for SETS), but results in twice
      as many positive/negative couples as SETS couple screening. The maximum number of
      carrier couples identified when screening 100,000 couples would be 88, resulting
      in a decrease of the number of children with CF of 25 each year. The costs of
      screening equal the savings if approximately 8,000 couples are screened yearly in
      the Netherlands. CONCLUSIONS: There are no financial objections to
      preconceptional couple screening in the Netherlands, even with an uptake ratio of
      around 10%. Whether screening for CF carriers should be offered or not should be
      decided on the basis of non-financial arguments.

PMID- 9623145
TI  - [Knowledge about drugs used by adult patients with asthma for self-treatment].
AB  - OBJECTIVE: To assess the knowledge of adult asthmatics about medication for self
      treatment. DESIGN: Descriptive. SETTING: Department of Pulmonary Diseases,
      Medisch Spectrum Twente, Enschede, the Netherlands. METHODS: As a part of a
      larger project aimed at improvement of self-management and self-treatment, all
      adults aged 18-65 years in Enschede (population 146,000) reported by the city
      pharmacists as using medication for asthma or chronic obstructive pulmonary
      disease, in 1994 were sent a questionnaire including 7 items pertaining to
      knowledge about lung medication. From among those who failed to respond after a
      written reminder and an appeal in local papers, a random group of 9% were
      interviewed by telephone. Of the responders who reported that according to their
      GPs they had asthma and who had answered the questions on medication, the number
      of questions answered correctly was counted; in addition, the question was
      investigated whether their level of knowledge was related to sex, education, use
      of (inhalation) corticosteroids and the form of explanation received. RESULTS: A
      total of 4563 questionnaires were sent out: 2259 (50%) usable forms were
      returned. The responders were better educated than the 192 non-responders
      interviewed, but did not differ as to age or sex. Of the responders, 1262 (56%)
      reported that their GPs had told them they had asthma. On average they had
      answered 2.4 (range: 0-7) out of 7 questions correctly. Previous instruction,
      number of sources of information, duration of taking medication, use of inhaled
      steroids, female sex and better education were all positively related with a
      higher knowledge score in this group. CONCLUSION: Adult asthmatics did not have
      sufficient knowledge about their medication. Improving such knowledge should
      therefore be an important element in the development of a self-management
      programme.

PMID- 9623146
TI  - [Phyllodes tumor in the breast].
AB  - In three women aged 51, 37 and 58 years, with a palpable tumour in the breast,
      excision and pathological examination led to the diagnosis of 'phyllodes tumour'.
      During 3-5 years after radical excision, in one patient followed by radiotherapy,
      no recurrences were seen. This rare breast tumour with a variable clinical course
      usually affects women between the ages of 30 and 50. There is often a large
      tumour and (or) rapid growth. Mammography and ultrasound are unhelpful
      diagnostically. Cytology is unreliable as the tumour is heterogeneous.
      Histologically the tumour can be benign, borderline malignant or malignant.
      Surgical excision with a margin of > or = 1 cm is the therapy of choice. The risk
      of recurrence after insufficient excision is considerable and histological
      deterioration can occur. Multiple samples, examination of resection margins and
      investigation into atypia, mitotic activity and stromal overgrowth are essential
      for making a prognosis and a treatment plan. In case of doubt regarding
      radicality, surgeon and pathologist should compare views; non-radicality
      necessitates re-excision.

PMID- 9623147
TI  - [How can I keep up with my literature?].
AB  - To keep up with the literature, the author and his wife have personal home
      subscriptions to the 'big five' general medical journals, two top general science
      journals, and close to a dozen specialist journals. Two of the general medical
      journals are regularly read in more depth. Since computerized search systems
      permit almost immediate retrieval on whatever subject at whatever work location,
      the author keeps no filing system of the items of interest. For three (slowly
      growing) subjects that transgress the boundaries of the usual keywords of search
      systems, copies of papers are collected in piles: (a) important methodological
      papers (which may have been published anywhere, on any subject), (b) papers about
      concepts of the origin and evolution of diseases, and (c) papers of strong
      general interest. The disadvantage of not keeping track of the literature by a
      personal filing system is that the author regularly forgets about papers and
      books he already has; the advantage is that no time is spent keeping a personal
      filing system.

PMID- 9623148
TI  - [Reference manager: a personal database on literature for consultation and word
      processing].
AB  - The software programme Reference manager serves as a personal database for
      bibliographic references within a restricted field, especially journal articles
      (with abstracts). Yet it is more than a digital card index. References can be
      retrieved via author name, keyword, title word, year of publication, or name of
      periodical. During the preparation of a manuscript by means of a word processor,
      references can be simply indicated by one or more of these characteristics. Later
      Reference manager transforms these provisional references automatically into a
      bibliography and text references, according to the style of the journal in
      question. The personal database does not have to be built through laborious
      copying, but can be captured from Medline databases. Updating with recent
      references is possible by means of bibliographic services such as Current
      contents or Reference update.

PMID- 9623149
TI  - [Consensus on antithrombotic prophylaxis of vascular events in patients with
      manifested atherosclerotic vascular disease].

PMID- 9623150
TI  - [The treatment of asthma in children: revised guidelines from pediatric
      pulmonologists].

PMID- 9623151
TI  - [Sudden death in young men due to arrhythmogenic right ventricular dysplasia].

PMID- 9623152
TI  - [Median neck cysts].

PMID- 9623153
TI  - [Coughing and wheezing children: improvement after parents stop smoking].
AB  - Three children, boys aged 6, 4 and 4 years presented with recurrent cough and
      (or) wheeze. Exposure to tobacco smoke at home was considered an aggravating
      factor. Symptoms in all three cases improved considerably or resolved completely
      when the patients' (grand)parent(s) stopped smoking. There is little literature
      on the beneficial effect of parents' giving up smoking on symptoms of childhood
      asthma. These cases, however, illustrate that advising parents of children with
      recurrent respiratory symptoms to give up smoking can be a rewarding and
      successful form of therapy.

PMID- 9623154
TI  - [Inhalation of sodium cromoglycate through a spacer device: no effect on symptoms
      in preschool children with moderate asthma].
AB  - Recently a randomised placebo controlled trial in a general practice setting
      showed that inhaler therapy with a spacer device in 218 1-4 year old children
      with moderate asthma is feasible, but that treatment with cromoglycate was no
      more effective than placebo. The lack of benefit from the treatment with
      cromoglycate may have resulted from several points discussed and refuted in this
      commentary. Major points are the degree of asthma of the children and uncertainty
      about the amount of medication that reached the lungs. The results of the trial
      support the intentions of national and international guidelines to withdraw the
      recommendation of cromoglycate as the first choice in prophylactic asthma
      treatment.

PMID- 9623155
TI  - [The cochlea: modern physiologic insights into sensorineural hearing loss].
AB  - The cochlea is organized tonotopically: each frequency between 20 Hz and 20 kHz
      has its own location on the basilar membrane. In addition the cochlea has a large
      dynamic range (sound intensity). Active movements of the outer hair cells of the
      sensory organ of Corti play a crucial part in determining hearing acuity and
      frequency selectivity. Long-known properties such as combination tones and more
      recent observations like spontaneous and evoked otoacoustic emissions (the
      cochlea as sound source) fit in the same concept of a cochlea acting as a non
      linear fine-tuned amplifier. Most sensorineural losses in people with diminished
      hearing are caused by injury to the hair cells, e.g. by medicines. Damage of
      outer hair cells impairs the cochlear amplifier, leading to loss of sensitivity
      to soft sounds and loss of frequency selectivity. Damage to the inner hair cells
      has much the same effect as conductive hearing loss. Tinnitus is not caused by
      otoacoustic emissions, but probably by denervation hypersensitivity following
      loss of cochlear input.

PMID- 9623157
TI  - [Gene therapy for hemophilia: feasible in principle but not yet clinically
      applicable].
AB  - The current treatment of haemophiliacs consists of injection of concentrates of
      blood clotting factors VIII (haemophilia A) and IX (haemophilia B). The
      inconvenience of the multiple injections needed, and the risk of transmission of
      infectious agents (HIV, hepatitis) prompted the development of alternative
      therapies. Gene therapy aims at introducing functional factor VIII and IX genes
      into the body cells of patients in order to make these cells produce the desired
      clotting factors. There are two strategies for gene therapy: (a) in the
      laboratory cells of the patient may be provided with the desired gene, followed
      by reintroduction of the cells that now produce factor VIII, into the patient (ex
      vivo strategy); (b) vectors with the desired genes may be injected into the
      patient in order to induce the modification (in vivo strategy) For both routes,
      the formal proof-of-principle has been acquired recently in animal experiments:
      cells modified by factor VIII or IX genes will produce adequate concentrations of
      the clotting products in plasma and will correct the bleeding tendency. Before
      the clinical evaluation and widespread application of the technology can be
      considered many technical problems have to be solved.

PMID- 9623159
TI  - [Twenty years of childhood coeliac disease in the Netherlands: more diagnoses and
      a changed clinical picture].
AB  - OBJECTIVE: To assess the incidence of childhood coeliac disease in the
      Netherlands and to study the clinical features. DESIGN: Prospective. SETTING:
      Leiden University Medical Centre, Leiden, the Netherlands. METHOD: Cases of
      childhood coeliac disease in the Netherlands in 1993-1995 were identified by
      means of the Dutch Paediatric Surveillance Unit. Inclusion criteria were: birth
      in the Netherlands, diagnosis with at least one small bowel biopsy in 1993-1995
      and age at diagnosis 0-14 years. The data were cross checked with the Dutch
      Network and National Database of Pathology and compared with data from a previous
      study on childhood coeliac disease, 1975-1990. RESULTS: 297 Coeliac patients were
      identified by means of the Surveillance Unit, another 32 through the National
      Database of Pathology. The mean crude incidence rate of diagnosed childhood
      coeliac disease was 0.51/1000 live births, which was in the range of rates found
      in other West European countries and significantly higher than the mean crude
      incidence rate of 0.18/1000 live births found in the Netherlands in 1975-1990.
      The clinical presentation was classic up to 1990: chronic diarrhoea, abdominal
      distention and growth failure. From 1993 onward, however, the number of children
      with chronic diarrhoea and abdominal distention decreased significantly and the
      number with weight loss, anaemia and abdominal pain increased. Associated
      disorders were present in 13.7% of the cases. CONCLUSIONS: The incidence of
      diagnosed childhood coeliac disease in the Netherlands showed a tendency to
      increase significantly during the past decade. In a period of 20 years a
      significant trend toward change in the clinical presentation of coeliac disease
      in Dutch children was observed.

PMID- 9623158
TI  - [Sealing esophagobronchial fistulae: better results with self expanding stents
      than with an esophagobronchial fistula].
AB  - OBJECTIVE: To compare the results of plastic endoprostheses and of self expanding
      stents in patients with an esophagobronchial fistula. DESIGN: Retrospective,
      descriptive. SETTING: Nederlands Kanker Instituut/Antoni van Leeuwenhoek
      Ziekenhuis, Amsterdam, the Netherlands. METHOD: Forty-two patients with an
      esophagobronchial fistula caused by a malignant tumour in the oesophagus, lungs
      or mediastinum were fitted with an endoprosthesis during the period 1 January
      1991-31 August 1995. Use was made initially of a plastic endoprosthesis with a
      special tulip funnel (n = 24), later of a coated self expanding stent (n = 18).
      In seven patients, the fistula had been the first manifestation of the tumour; in
      35, a recurrence after earlier treatment was involved. The initial
      characteristics (sex, age, diagnosis, earlier therapy, signs and symptoms) were
      the same in both groups. RESULTS: Dilatation immediately before insertion of a
      plastic endoprosthesis was necessary in 23 patients (96%); such dilatation was
      necessary in four of the patients (22%) fitted with a self expanding stent.
      Complete sealing of the fistula was achieved in 19 (79%) and 15 (83%) patients,
      respectively. Reoperations were necessary in eight (33%) and three (17%)
      patients. Early major complications occurred in four (17%) and two (11%)
      patients. CONCLUSION: The selfexpanding stent was faster and easier to insert
      than a plastic endoprosthesis, and effective in sealing an oesophagobronchial
      fistula.

PMID- 9623160
TI  - [Efficiency of mixed RASTs in serological screening of possibly allergic
      patients].
AB  - OBJECTIVE: To determine the age distribution of results of serological allergy
      screening using mixed-allergen radioallergoabsorbent tests (RASTs), and to
      determine the cost-effectiveness of mix RASTs. DESIGN: Retrospective. SETTING:
      University Hospital of Rotterdam; Dijkzigt Hospital and Sophia Children's
      Hospital, the Netherlands. METHODS: An analysis was made of the results of all
      determinations requested in a period of 3 years with use of the CAP Phadiatop
      test (aimed at IgE against a mixture of inhalant allergens) and the CAP f x 5
      food mix test (aimed at IgE against a mixture of food allergens). RESULTS: The
      CAP Phadiatop test was positive most strongly and most frequently in patients
      aged 7 to 30 years. From the age of 2 years, there was a sharp rise of the number
      of positive CAP Phadiatop tests, but IgE against inhalant allergens was also
      found in over 10% of the children aged 0 and 1 year. Up to and including the age
      category of 6 years, over one-third of the sera submitted had a positive CAP f x
      5 food mix test. From a budget point of view, preliminary screening with a mix
      RAST is the more advantageous the lower the allergy prevalence and the higher the
      mean number of CAP-RASTs to be requested per serum. CONCLUSION: A substantial
      saving of laboratory costs can be achieved by having mix RASTs such as CAP
      Phadiatop and CAP f x 5 food mix tests precede determinations of specific IgE
      against separate allergens; these savings will be the higher the smaller the
      proportion of positive results and the higher the mean number of separate RASTs
      to be requested per serum.

PMID- 9623161
TI  - [Treatment of Frey's syndrome with botulinum A toxin].
AB  - A 74-year-old woman suffered from severe gustatory sweating and flushing of the
      preauricular skin following parotidectomy (Frey's syndrome). She was treated with
      intracutaneous botulinum A toxin injections in the affected skin area. Minor's
      test was used to determine the extent of the affected area. Within one week, the
      symptoms disappeared. After three weeks, Minor's test was repeated and showed
      minimal residual hyperhidrosis. These small areas were treated again. No side
      effects were noted. At follow-up one year later, the patient was free of
      symptoms.

PMID- 9623162
TI  - [The 'railway spine': alleged spinal injury caused by railway concussions as a
      basis for financial claims in 19th century England].
AB  - The diagnosis 'railway spine' was a predominantly 19th century British
      phenomenon, with faint echos in the Netherlands. The diagnosis was controversial.
      Train accidents gave rise to litigation in compensation cases in which
      posttraumatic symptoms with no apparent lesions were related to molecular spinal
      damage. Medical opinion differed about the physical or psychic nature of the
      symptoms. The diagnosis was strongly associated with fraudulent claims for
      compensation and became obsolete after 1900, when the symptoms were generally
      diagnosed as a functional neurosis. The railway spine controversy was a precursor
      of the modern discussion concerning the validation of posttraumatic symptoms.

PMID- 9623163
TI  - [The contribution of general practice medicine to undergraduate medical
      education].
AB  - The Blueprint 1994. Objectives of undergraduate medical education, was issued in
      1994 and has since been used as a guideline by the eight medical faculties in the
      Netherlands. This prompted a team of representatives of all eight Institutes for
      General Practice Medicine of the country to describe the contribution of general
      practice medicine to undergraduate medical education. The team was guided by two
      basic principles of general practice medicine, viz. general accessibility for all
      health problems at all stages and the continuous nature of the care. Out of the
      180 general objectives of the Blueprint, 12 were selected of which the teaching
      should preferably be provided or coordinated by general practice medicine. Out of
      the approximately 250 problems from the general problem list of the Blueprint,
      134 were assigned to general practice medicine: 89 in view of their high
      incidence in general practice, 15 because of the emergency nature, since GPs are
      easily accessible, 12 in which a major disease has to be excluded and 18
      regarding chronic conditions. In this way, insight is provided into the matters
      regarding which medical faculties can address departments of general practice
      medicine about the curriculum to be drawn up. It appears advisable that other
      specialisms as well should define their potential contributions to undergraduate
      medical education and the relevant priorities.

PMID- 9623164
TI  - [Relative adrenocortical insufficiency in intensive care patients].
AB  - Unexplained shock developed after a major vascular operation in a man aged 67 who
      used inhalation corticosteroids for a chronic obstructive pulmonary disease, and
      after pancreaticoduodenectomy in a man aged 56. Both had relative adrenocortical
      insufficiency, combated with corticosteroid supplementation. The condition of a
      relative adrenocortical insufficiency is considered to exist if a test dose of
      corticosteroids leads to rapid weaning from sympathicomimetics. A subnormal rise
      of plasma cortisol after stimulation with adrenocorticotropic hormone supports
      the diagnosis. Routine corticosteroid substitution in intensive care patients is
      inadvisable, because it enhances the risk of complications related to use of
      steroids.

PMID- 9623165
TI  - [Early exclusion of ischemic myocardial damage made possible by new biochemical
      cardiac markers].
AB  - New immunochemical assay methods for the cardiac markers creatine kinase (CK) MB
      mass, myoglobin, troponin T (TnT), troponin I (TnI), fatty acid binding protein
      (FABP) necessitate re-evaluation of their usefulness in the early diagnosis of
      myocardial damage. Cardiac markers play an important part in the exclusion of
      myocardial damage in patients with chest pain and an inconclusive ECG at
      admission. A serial CK-MB mass determination is particularly suitable for this
      exclusion of myocardial damage. The sensitivity of TnT shortly after an
      infarction is comparable with that of CK-MB mass; a single determination on
      admission is insufficient. The marker myoglobin is of limited value owing to the
      brief duration of myoglobin rise and insufficient heart specificity. An increased
      TnT or TnI value in patients with unstable angina pectoris is a prognostically
      negative sign. It is still not clear how this prognosis can be improved. A
      negative troponin finding appears not to exclude early complications. The
      department of Emergency Cardiac Care of the Academic Medical Centre, Amsterdam,
      the Netherlands, currently prefers the serial measurement of the CK-MB mass, in
      the future possibly to be supplemented by a troponin determination.

PMID- 9623166
TI  - [Diagnosis and therapy of patients with adrenocortical insufficiency].
AB  - Most symptoms and signs of adrenocortical insufficiency are aspecific. For a
      definitive diagnosis a stimulation test is often needed. In case of secondary
      adrenocortical insufficiency glucocorticoid substitution nearly always suffices.
      Patients with primary adrenocortical insufficiency need substitution not only
      with glucocorticoids but also with mineralocorticoids. A standard daily dose of
      30 mg hydrocortisone as glucocorticoid substitution is too high for many
      patients, while for some a standard daily dose of 0.1 mg fludrocortisone as
      mineralocorticoid substitution is too low. Patients with adrenocortical
      insufficiency need adequate instructions about what to do in case of stress, such
      as a (febrile) illness or trauma. Duration and severity of the suppression of the
      pituitary-adrenal axis by the use of pharmacological amounts of glucocorticoids
      are highly variable. When pharmacological amounts of glucocorticoids (> 7.5 mg
      prednisone daily) are used for 3 weeks or longer, a clinically relevant
      suppression of the pituitary-adrenal axis is possible, and this may persist for
      one year after discontinuing the use of glucocorticoids.

PMID- 9623167
TI  - [Optimizing antibiotics use policy in the Netherlands. I. The Netherlands
      Antibiotics Policy Foundation (SWAB)].
AB  - The worldwide problem of antibiotic resistance of bacteria is a point of concern
      in the Netherlands as well. Responsible use of existing antibiotics was the
      incentive to establish a foundation, with the acronym SWAB, the primary goal of
      which is to optimize the use of antibiotics in the Netherlands in order to
      diminish the development of antibiotic resistance. One of the SWAB projects is
      the development of national guidelines for the use of antibiotics in hospitals.
      These guidelines are prepared by a committee of experts and reviewed by external
      consultants: infectious disease specialists, medical microbiologists and
      pharmacists. The revised version of the guidelines is submitted for publication
      in this journal. The SWAB hopes that these guidelines will make the prevention of
      antibiotic resistance a major factor in the choice of the antibiotic.
      Streamlining antibiotic therapy is an important tool in this respect.

PMID- 9623168
TI  - [Optimization of the antibiotics policy in the Netherlands. II. SWAB guidelines
      for the antimicrobial therapy of pneumonia in patients at home and as nosocomial
      infections. The Netherlands Antibiotic Policy Foundation].
AB  - The Netherlands Antibiotic Policy Foundation issued guidelines for empirical
      antimicrobial therapy of adult pneumonia patients in hospitals. A distinction is
      made between pneumonia contracted at home or in hospital because of the
      differences in micro-organisms and resistance patterns. These two categories are
      subdivided further with an empirical antibiotic treatment being chosen on the
      basis of the causative agents to be expected. For instance, pneumonia contracted
      at home is mostly caused by Streptococcus pneumoniae, to be treated with
      benzylpenicillin or amoxicillin. With regard to nosocomial pneumonia, treatment
      varies according to whether a pneumonia has or has not been contracted in the
      intensive care unit. Combating development of resistance is alloted an important
      place. Emphasis is laid on 'streamlining' the therapy, i.e. its adjustment
      (including choosing an antibiotic with the narrowest possible spectrum) once the
      causative agent is known.

PMID- 9623169
TI  - [The evaluation of the lung transplantation program at Groningen: survival rate,
      quality of life, and cost-effectiveness].
AB  - OBJECTIVE: Assessment of the effectiveness and cost-effectiveness of lung
      transplantation, and the supply and need of donor lungs in the Netherlands.
      DESIGN: Prospective and comparative. SETTING: University Hospital Groningen, the
      Netherlands. METHOD: Costs and effects were compared of the situations with and
      without a lung transplantation programme. Costs and effects were registered
      during all phases of this programme (November 1990 to February 1996; 76 patients
      reached the transplantation phase), and the situation without a programme was
      judged on pre-transplant evidence. The effect of lung transplantation on survival
      was assessed by means of a Cox regression model, and in the quality of life study
      of a longitudinal analysis was applied. The supply and the need of donor lungs
      were based on several registrations. RESULTS: Lung transplantation led to a
      significant improvement in survival and quality of life. The average gain in life
      years and quality adjusted life years (Qalys) were estimated at 4.4 and 5.2,
      respectively. The average costs per transplanted patient were estimated at Hfl.
      670,000 (Hfl. 1 is about 0.5 dollar). The average costs per life year and Qaly
      gained were estimated at Hfl 153,000 and Hfl. 120,000 (both discounted),
      respectively. The annual need of donor lungs was estimated at 50-75, the annual
      supply at 17-27. CONCLUSIONS: Lung transplantation leads to improvement of
      survival and quality of life. However, it involves considerable costs and the
      cost-effectiveness is unfavourable compared with other Dutch transplant
      programmes. Moreover, there is a great discrepancy between the need and supply of
      donor lungs in the Netherlands.

PMID- 9623170
TI  - [The elevation of serum creatine kinase-MB level in trauma patients: misleading
      impression of myocardial damage].
AB  - OBJECTIVE: To determine the frequency of increase of serum values, not of cardiac
      origin, of creatine kinase-MB (CK-MB) in trauma patients. DESIGN: Prospective.
      SETTING: University Hospital, Groningen, the Netherlands. METHODS: 51 trauma
      patients without chest injury (without myocardial contusion) but with (among
      others) soft tissue injuries, were included. At admission (time point t1) an ECG
      and chest X-ray were made and blood was collected for measurement of CK total, CK
      MB activity and CK-MB mass. If the CK-MB activity/CK total fraction exceeded 3%,
      CK electrophoresis was performed. Blood analysis was repeated after 24 hours
      (t2). RESULTS: CK-MB activity was elevated in 27 patients (53%) at t1 and in 3
      (6%) at t2. The fraction CK-MB activity/CK total exceeded 3% in 96% and 33% of
      these patients at t1 and t2, respectively. In all these cases a CK-BB band was
      detected by electrophoresis (CK-BB interferes with the CK-MB activity
      measurement). CK-MB mass was elevated in 11 patients (22%) at t1 and in 19 (37%)
      at t2. CONCLUSION: CK-MB was frequently elevated in trauma patients owing to
      skeletal muscle damage and to interference with CK-MB activity measurements. For
      the detection of myocardial damage in trauma patients, CK-MB measurements are of
      little use.

PMID- 9623171
TI  - [Infections with Mycobacterium kansasii in the Academic Medical Center in
      Amsterdam: the changing clinical spectrum since the start of the HIV epidemic].
AB  - OBJECTIVE: Inventory of patients with a Mycobacterium kansasii infection. DESIGN:
      Descriptive, retrospective. SETTING: Academic Medical Centre, Amsterdam, the
      Netherlands. METHOD: Review of the medical records of all patients with a
      bacteriologically confirmed infection with M. kansasii from January 1987 until
      the end of December 1996. RESULTS: M. kansasii was isolated from 17 patients. Of
      15 HIV-tested patients 13 were seropositive. Their median CD4 count was 10 x
      10(6)/l. Ten HIV-positive individuals used trimethoprim-sulfamethoxazole
      prophylaxis. In 1 HIV-seropositive and in 1 HIV-seronegative patient no chest X
      rays were made. Caverns were present in none of 12 HIV-positive patients and in 1
      of 3 HIV-negative patients. Of the HIV-positive patients 1 fulfilled the criteria
      for pulmonary infection of the American Thoracic Society (ATS). According to
      these criteria 9 of the HIV-positive patients were colonized with M. kansasii. In
      6 of these patients there were indications of infection: regression of pulmonary
      infiltrates with therapy (n = 3), positive histology and culture of lung tissue
      at autopsy (n = 1), and dissemination (n = 2). Disseminated infection occurred in
      a total of 4 HIV-infected patients. CONCLUSION: HIV-infected patients are at an
      increased risk for M. kansasii infection. Trimethoprim-sulfamethoxazole does not
      offer protection against this infection. The diagnostic criteria of the ATS are
      not applicable to these patients. M. kansasii infection confirmed by isolation in
      an HIV-positive individual should always be treated.

PMID- 9623172
TI  - [Mycobacterium genavense infection in 2 HIV seropositive patients in Amsterdam].
AB  - Two patients with an HIV-I infection, a man aged 47 with confusion, aphasia and
      diarrhoea, and a man aged 32 with dysphagia, a non-productive cough and
      diarrhoea, were diagnosed as having a disseminated Mycobacterium genavense
      infection. Both had low counts of CD4+ T lymphocytes. They responded to
      antimycobacterial treatment. M. genavense was recognized in Geneva in the early
      nineties as a causative agent of disseminated mycobacterial infections in HIV
      seropositive patients with poor cellular immunity. The clinical picture resembles
      that of a generalized infection with M. avium-intracellulare. M. genavense is a
      slowly growing mycobacterium which can be isolated and identified using enriched
      nutrient media and molecular-biological techniques. The infection probably begins
      in the gastrointestinal tract after oral contamination. DNA of M. genavense can
      be demonstrated in 25% of the intestinal biopsy samples of non-HIV-seropositive
      patients.

PMID- 9623173
TI  - [The global eradication of polio by the year 2000].
AB  - The World Health Organization wants to attain global eradication of poliomyelitis
      in the year 2000. In all countries commissions are installed to document polio
      free certification. Four activities are considered vital by the WHO to achieve
      this goal: (a) strict surveillance of all suspected cases of poliomyelitis, (b)
      close clinical and virological examination of all children younger than 15 years
      with acute flaccid paralysis (AFP), (c) laboratory surveillance of poliovirus
      isolates and (d) surveillance of sewage. The Netherlands has been selected as
      example country for the certification process. However, the AFP surveillance is
      not yet optimal, therefore all physicians are asked to join in the effort.

PMID- 9623174
TI  - [The Health Research Promotion program (SGO). XII. Evaluation of the section
      'Health Care Research-experimental postgraduate training of general
      practitioners'].
AB  - As a part of the SGO Health Research Promotion Programme, programme section
      Health Care Research, an experimental core training was instituted for general
      practitioners. The aim of the training was to provide a small number of family
      physicians with clinical and medical expertise relevant to general practice that
      would enable them to play a leading role in the development of academic general
      practice medicine. Seven general physicians followed a self-composed training
      programme of 2 to 3 years, consisting of active participation in patient care in
      Dutch clinics and clinics in other countries. The experiences gained during the
      SGO programme were used by the Dutch College of General Practitioners to develop
      a nationwide superior professional training course.

PMID- 9623175
TI  - ['Smart drugs' enticements on the Internet].
AB  - 'Smart drugs' are drugs supposed to enhance certain physical or mental functions,
      without harmful side effects. The target group for the misleading advertisement
      campaigns on the Net is mostly the younger generation. Smart drugs clearly are
      pharmacologically active: phenytoin, selegilin and growth hormone are examples of
      compounds that can be ordered from mail order pharmacies without prescription.
      Misleading medical information on the Internet is undesirable and potentially
      harmful and the widespread availability of smart drugs should be realised by
      pharmacists and physicians. Screening the Net for this kind of information should
      be implemented as a standard procedure and specific, targeted information to put
      these drugs in a realistic perspective could be the first step leading to
      'debunking' the Internet.

PMID- 9623176
TI  - [Risk factors for the development of phlebitis during intravenous infusion].

PMID- 9623177
TI  - [What is the significance of the new American guidelines for the diagnosis of
      diabetes mellitus for the Netherlands].

PMID- 9623178
TI  - [Kimura's disease].

PMID- 9623179
TI  - [The second revision of consensus with respect to blood transfusions].

PMID- 9623180
TI  - [Right-sided diverticulitis mimicking acute appendicitis].
AB  - The probability diagnosis in two patients, women aged 43 and 41 years, who for
      the last few days had had pain in the right lower abdomen, without nausea or
      vomiting, was acute appendicitis; a third patient, a woman aged 49 with the same
      symptoms, had undergone appendectomy in the past. Peroperative findings and, in
      two patients, microscopy of the resected specimen showed diverticulitis in the
      caecum or ascending colon. This is an uncommon disease, which mimicks acute
      appendicitis. Treatment depends on the severity of the inflammation. In the
      absence of perforation or abscess, conservative treatment suffices. Otherwise,
      resection of the colon is necessary.

PMID- 9623182
TI  - [Less fat or a different fat?].
AB  - Current dietary advice with a view to avoiding cardiovascular pathology is to
      replace fatty foodstuffs and those rich in saturated fat and cholesterol by food
      rich in complex carbohydrates. Although substitution of carbohydrates for fat
      lowers the blood level of low-density lipoprotein (LDL) cholesterol, it also
      lowers the level of high-density lipoprotein (HDL) cholesterol, thereby adversely
      influencing the risk profile for cardiovascular disease. Neither does a low fat
      diet appear to reduce obesity, another risk factor. A modern advice based on
      published research reads: obese persons should reduce their intake of saturated
      and trans-fatty acids by lowering the consumption of dairy fat, meat and hardened
      oils (bakery products and catering products fried in hardened fats), and in
      addition should consume less products with added sugars and refined starch.
      Carbohydrates should be provided by fruits, vegetables, leguminous plants and
      whole-wheat products. Persons of about the ideal weight should replace saturated
      and trans-fatty acids in their diet by unsaturated plant oils, and products with
      refined carbohydrates by fruits, vegetables and whole-wheat products.

PMID- 9623181
TI  - [Reflux esophagitis; is the preventive eradication of Helicobacter pylori needed
      in patients on omeprazole?].
AB  - The pattern of Helicobacter pylori gastritis depends on acid secretion. Profound
      acid suppressive therapy with proton pump inhibitors leads to a decrease of
      antral gastritis, but an increased severity of corpus gastritis. As such,
      maintenance therapy with these drugs for gastroesophageal reflux disease has
      consistently been associated with an increased incidence of atrophic gastritis in
      H. pylori infected patients. For this reason, the preventive effect of H. pylori
      eradication in these patients needs to be considered; this is being studied in
      prospective trials.

PMID- 9623183
TI  - [Wasp and bee venom allergy].
AB  - To diagnose insect venom allergy a good patient history is important.
      Allergological tests (skin test, specific IgE titre) confirm the diagnosis.
      Patients are advised on preventive measures (e.g. with respect to clothing and
      use of perfume). They are also instructed on medical treatment (antihistaminics,
      epinephrine) in case they are stung again. In patients having had a serious
      systemic reaction immunotherapy should be considered. Immunotherapy leads to
      complete protection in more than 98% of patients with wasp (yellow jacket) venom
      allergy and in 75-80% of patients with bee venom allergy. Serious adverse
      reactions to immunotherapy are rare. Immunotherapy lasts at least 3 to 5 years.
      After cessation of immunotherapy the frequency of systemic reactions to the sting
      of a wasp or bee is in the range of 5-15%. There are insufficient data on the
      long-term effect of immunotherapy.

PMID- 9623184
TI  - [Bone transplantation and bone replacement materials].
AB  - There is a growing need for immediately available material with appropriate
      qualities for reconstruction of large bone defects. Autologous spongy bone grafts
      are optimal as to biocompatibility, but are in short supply. Allogenic and
      xenogenic bone grafts evoke an immunological reaction after implantation and are
      not biocompatible. In the last thirty years ceramic implants and composites have
      been developed for bone substitution. New calcium phosphate bone substitutes
      undergo processes of resorption and precipitation of carbonate apatite that play
      a part in formation of new bone. These materials are easy to use because of their
      pastelike consistence. Resorption properties are influenced by particle size,
      crystallinity and composition. So far, no serious adverse reactions were
      reported. More clinical experience is necessary especially with composites and
      combinations with antibiotics, bone growth factors and collagen, to specify the
      place of these modern calcium phosphates in bone replacement and bone
      substitution.

PMID- 9623185
TI  - [Alarm training also successful in 5 to 7 year olds with nocturnal enuresis].
AB  - OBJECTIVE: To determine how many bed-wetting children aged 5-7 years unlearn the
      habit using the alarm treatment. DESIGN: Descriptive. SETTING: TNO Prevention and
      Health, Leiden, the Netherlands. METHODS: The population consisted of all
      children aged 5 to 7 with nocturnal enuresis (defined as > or = 2 wettings per
      week) who ordered an Elther alarm set (Elther BV, Tilburg) in May or June 1996 (n
      = III). The parents and the child were asked to keep notes during the treatment
      of whether the child had remained dry and of whether the alarm had sounded. When
      at the time of cessation of the alarm training the results were insufficient, the
      parents were asked about the reason to stop. When the child had remained dry for
      14 nights in succession (the definition of 'success'), a questionnaire was sent 6
      months later to inquire if the child was still dry or had relapsed. RESULTS: The
      totals of success for children aged 5, 6 and 7 years were 70% (n = 7/10), 73% (n
      = 29/40) and 90% (n = 55/61), respectively. Seven-year-olds were significantly
      more successful than the children aged 5 or 6 (p = 0.02). No significant
      correlations were found between results of treatment and sex, the nature of the
      enuresis (purely functional or not), familial occurrence and frequency of bed
      wetting at the start of the treatment. The average times until success were 53
      days for the 5-year-olds (range: 31-78), 65 days for the 6-year-olds (26-154) and
      59 for the 7-year-olds (17-141). The proportions of relapse after 6 months were
      0%, 14% and 9%, respectively. CONCLUSION: Alarm training with pad and buzzer
      appears to be a suitable method of treatment even for children younger than 8
      years.

PMID- 9623186
TI  - [Nothing gained from the determinations of plasma lactate levels in the
      evaluation of a patient with acute abdomen].
AB  - OBJECTIVE: To establish the diagnostic value of laboratory tests, especially the
      plasma lactate concentration, for determination of the indication for acute
      surgery in patients with an acute abdomen. DESIGN: Cross-sectional study.
      SETTING: Kennemer Gasthuis, location Elisabeth Gasthuis, Haarlem, the
      Netherlands. METHOD: The study group consisted of all 200 successive patients
      presenting at the emergency room with acute abdomen from June 1993 to December
      1994 (19 months). Patients with suspected acute appendicitis were excluded. The
      diagnosis and indication for surgery if any were based on case history, physical
      examination, radiological examination if performed and standard laboratory tests:
      ESR, leukocyte count, haemoglobin, creatinine and amylase. The first matter
      considered was to what extent the indication for acute operation based on these
      clinical criteria was in agreement with the diagnosis at discharge. The next
      question studied was what would be the extra value of the plasma lactate
      concentration which, although determined, had not been reported to the clinician.
      Statistical analysis was performed using the two-sample Student t test and the
      chi 2 test. A p-value of < 0.05 was regarded as statistically significant.
      RESULTS: Fifty-four patients were operated within 24 hours for good reasons, six
      were incorrectly not operated within 24 hours, 128 correctly received
      conservative treatment and 12 were correctly treated conservatively and
      subsequently underwent operation after longer than 24 hours. Diagnostics based on
      the clinical criteria had a sensitivity of 90%. The mean plasma lactate
      concentration, temperature and ESR were statistically significant more often
      increased in the operated patients than in those treated conservatively. The
      sensitivities of these determinations were 75%, 67% and 40% (all: p < 0.05). The
      lactate concentration was increased in 50% of the patients who in retrospect had
      incorrectly not been subjected to acute surgery. CONCLUSION: Neither
      determination of the plasma lactate concentration nor the results of the separate
      standard laboratory tests in acute abdomen patients resulted in a better
      sensitivity for the determination of an indication for acute surgery than
      clinical examination combined with standard laboratory tests and, if desired,
      supplementary radiology.

PMID- 9623187
TI  - [The detection of melanoma metastases in sentinel nodes by polymerase chain
      reaction].
AB  - OBJECTIVE: To investigate the possibility of detecting melanoma metastases using
      molecular biological techniques in patients with a primary malignant melanoma.
      DESIGN: Descriptive. SETTING: Reinier de Graaf Gasthuis Hospital Delft and
      diagnostic centre SSDZ Delft, the Netherlands. METHODS: A melanoma specific
      tyrosinase mRNA was amplified using the reverse transcriptase polymerase chain
      reaction (RT-PCR) technique. RESULTS: A total of 23 sentinel nodes derived from 9
      patients were examined. In 14 sentinel nodes metastases were found using RT-PCR.
      In microscopic slides stained with haematoxylin and eosin (HE) melanoma
      metastases were found in 2 sentinel nodes of 2 patients. With
      immunohistochemistry melanoma metastases were found in the same 2 sentinel nodes.
      CONCLUSION: It is possible to detect melanoma metastases in sentinel nodes using
      molecular biological techniques.

PMID- 9623188
TI  - [Giant urinoma of the thigh].
AB  - A man aged 70 during a hospital stay over a period of a few weeks developed
      increasing pain and swelling of the left thigh. Despite extensive diagnostic
      imaging and surgical drainage, initially no diagnosis could be established. After
      more than 3 months the tumour proved to be caused by leakage of urine from the
      pelvis to the soft tissues of the leg. Unfamiliarity of the clinicians with such
      an extension of an urinoma contributed to the considerable diagnostic delay.
      Introduction of a bladder catheter stopped the flow of urine to the leg and
      reduced the leg circumference.

PMID- 9623189
TI  - [Malaria prophylaxis; advice for the individual traveller. The Working Group for
      Malaria Prophylaxis].
AB  - Recently, the Dutch Working Group on Malaria Prophylaxis produced new national
      guidelines. The new approach takes the risk of malaria and of serious morbidity
      or mortality for the individual traveller as its point of departure. In large
      areas in the tropics, there is no malaria risk. In some areas with limited risk,
      proguanil is still an effective chemoprophylactic (mainly in Central America, the
      Near East, Central Asia and parts of Indonesia). However, multiple-drug resistant
      Plasmodium falciparum necessitates the use of mefloquine, despite disturbing side
      effects in some people, in Sub-Saharan Africa, major parts of South East Asia and
      the Amazone basin of South America. If mefloquine is contraindicated,
      alternatives advised are the combination of proguanil and chloroquine or (in
      South East Asia) doxycycline. For visits to transmission areas lasting 7 days or
      less, alternative prophylactic measures may be acceptable, but only if the
      traveller after the visit has easy access to adequate medical facilities. When
      exposure lasts not more than two nights, use of a mosquito net, repellents and
      protective clothing without chemoprophylaxis is acceptable, provided the
      traveller is well informed. To take along pocket treatment is only advised for
      some journeys lasting more than one month to areas with multiple-drug resistant
      falciparum malaria. When mefloquine prophylaxis is used, such stand-by treatment
      is only advocated for a few countries in South East Asia; when mefloquine cannot
      be given, also for other areas. The type of pocket treatment recommended depends
      on the chemoprophylaxis used and on whether contraindications exist. Drugs that
      can be used are: halofantrine (if no contraindications exist and an ECG shows no
      prolongation of the QT interval) or quinine, either alone (in pregnancy) or
      combined with doxycycline or clindamycine (the latter for children < 8 years).
      With the new individual approach advice may differ for different persons visiting
      similar tropical areas. It is the physician's task to explain the risks of a
      particular journey and the measures advised.

PMID- 9623190
TI  - [The seizure of medical records; views on the limits of confidentiality law].
AB  - In the Netherlands the seizure of a medical file by the justice department
      without the consent of the possessor of the file, is formally forbidden.
      Nevertheless, medical files are being seized occasionally for juridical reasons,
      to the distress of the medical profession. It is concluded that the possessor of
      a medical file cannot object before a court of law to the seizure by the justice
      department. There is a need to change Dutch law so that doctors or hospitals will
      in fact have that possibility.

PMID- 9623191
TI  - [Risk factors for the development of complications in children admitted with
      measles at a university hospital in the Philippines].

PMID- 9623192
TI  - [Isolated traumatic dorsal dislocation of the metacarpophalangeal joint of the
      index finger].

PMID- 9623193
TI  - [The hepatitis A epidemic in Heerlen, in 1996; the importance of immunization of
      migrant children].

PMID- 9623194
TI  - [The business of healing; the closure of wounds].

PMID- 9623195
TI  - [A classic case of infectious endocarditis?].

PMID- 9623196
TI  - [Hypertonic dehydration in "silent" malnutrition of breast-fed infants].
AB  - Two firstborn, breast-fed infants (delivery at home) were admitted to the
      hospital in a critical state of hypernatraemic dehydration. Case 1, a boy aged 13
      days, had suffered 1220 g loss of weight since birth (31%), his serum sodium
      concentration was 180 mmol/l. Case 2, a girl aged 7 days, had lost 610 g since
      birth (18%); her serum sodium level was 159 mmol/l. In both cases poor
      professional support of lactation and lack of weight control had resulted in
      unnoticed severe malnutrition. After slow rehydration recovery was uneventful.
      Closer monitoring of babies' weight, e.g. twice a week, is advocated especially
      for breast-fed firstborns in the early weeks of life.

PMID- 9623197
TI  - [Genetic carrier screening for hemoglobinopathies: the situation in the
      Netherlands compared with England].
AB  - In the Netherlands, in contrast to England, no screening for carriership of
      haemoglobinopathy (sickle-cell anaemia and thalassaemia) is being carried out.
      The absolute prevalence is low, but the prevalence in proportion to birth figures
      is approximately the same in the two countries. The lack of knowledge of the
      professional groups involved can be rectified by adequate instruction. The
      question whether screening should be carried out before pregnancy or early
      prenatally proved not difficult to solve in England. Screening for carriership is
      technically possible and in England it is also cost-effective. This screening
      should be performed in the Netherlands, as well.

PMID- 9623198
TI  - [One hundred years of orthopedics in the Netherlands. I. Introduction].
AB  - One hundred years ago, on 1 May 1898, the Netherlands Orthopaedic Association was
      founded. This was prompted by the view that general surgeons paid insufficient
      attention to the treatment of the locomotor system; they were permitted to join
      the new association, however, at any rate until 1947. It was especially in the
      last 30 years that orthopaedic surgery underwent major changes. The most striking
      novelty was arthroplastic surgery. There have also been developments in the
      treatment of spinal abnormalities, rheumatological surgery, sports medicine,
      oncology and traumatology.

PMID- 9623199
TI  - [One hundred years of orthopedics in the Netherlands. II. Treatment of
      fractures].
AB  - The treatment of fractures was originally conservative. Improvements in materials
      and surgical techniques and new insights into the biological aspects of fracture
      healing led to an increase of surgical treatment of fractures. The main
      breakthrough of osteosynthesis took place with the foundation of the
      Arbeitsgemeinschaft fur Osteosynthesefragen (Study Group for Problems in
      Osteosynthesis) which had as its basic principles anatomical repositioning,
      stable internal fixation, atraumatic surgical technique and early mobilization.
      In general, surgical treatment is indicated for periarticular fractures, open
      fractures, fractures complicated by nervous or vascular lesions, pathological
      fractures and fractures in multiple injury patients. The question who should
      practise traumatology, the general or the orthopaedic surgeon, was initially a
      point of controversy; by now, cooperative teams have been formed based on
      appreciation of one another's qualities. The trend for the near future appears to
      be minimally invasive surgery, with indirect repositioning and fixation
      techniques and biological methods of stimulating fracture healing.

PMID- 9623200
TI  - [One hundred years of orthopedics in the Netherlands. III. Bone tumors].
AB  - In the fifties, patients with a malignant bone tumour were treated with
      radiotherapy, sometimes supplemented by resection, as recommended by the Bone
      Tumour Committee established in 1953. In the seventies, improvement of imaging
      techniques and chemotherapy made limb-saving surgery possible. Currently, 70% of
      patients with a malignant tumour of the locomotor apparatus are treated by limb
      saving, oncologically justified surgery. The surgical defects can be repaired
      with the aid of an endoprosthesis, or bone homografting or autografting. Children
      are often treated with an operation involving 180% rotation of the ankle to
      function as the knee, combined with a prosthesis. Adults are sometimes treated
      with this technique, but also with internal ('standard') prostheses and donor
      bone. The future will have to make clear which technique is to be preferred in
      which situation. Probably, typing and prognosis of various tumours may improve,
      leading to better insight into the treatment. Centralization of the treatment of
      rare tumours may also contribute to improvement of the treatment and its
      scientific research.

PMID- 9623201
TI  - [One hundred years of orthopedics in the Netherlands. IV. Spinal abnormalities].
AB  - In recent years there has been spectacular progress in the approach to various
      disorders of the spinal column. Owing to improved methods of osteosynthesis there
      is no longer so much need for long periods of postoperative bed rest. Of all the
      scolioses, idiopathic scoliosis is most common. The vast majority of these cases
      are not clinically significant. What is seen in the remaining cases if left
      untreated is a progression in the curvature during growth. Progressive idiopathic
      scoliosis can be effectively treated using conservative methods. Screening at
      school is an important part of this process. If the curvature proves progressive
      and skeletal growth is not complete a brace can be prescribed. Use of this
      strategy and form of treatment can avoid progression of the curvature and
      development of serious deformities. This conservative therapy has markedly
      reduced the need for corrective surgery. Scheuermann's disease is characterized
      by a fixed dorsal thoracic kyphosis. Progressive Scheuermann's kyphosis can be
      effectively treated using a brace. The majority of fractures of the vertebral
      bodies can be treated conservatively. However, serious fractures normally require
      surgical intervention. In the industrialised Western world, low back pain is a
      major health problem and the foremost cause of disability and unfitness for work.
      Low back pain caused by degenerative disease of the spinal column should be
      treated using a multidisciplinary approach. The development of advanced operative
      techniques and osteosynthesis methods has made it possible to treat metastases of
      the spine surgically. The effects of this treatment on the quality of life are
      encouraging.

PMID- 9623202
TI  - [Channelopathies: a genetic explanation of migraine and other paroxysmal
      neurologic disorders].
AB  - There is increasing evidence of involvement of genes coding for ion channels in
      the pathogenesis of paroxysmal neurological disorders. Recently for instance,
      mutations in the calcium channel gene on chromosome 19 were identified in
      migraine, ataxia, and epilepsy. With the current research into inherited
      'channelopathies' a new approach has been established. A better understanding of
      the pathophysiology of paroxysmal neurological disorders may lead to new
      therapeutic strategies.

PMID- 9623203
TI  - [Genetic carrier screening for hemoglobinopathies in the Netherlands is not
      opportune].
AB  - OBJECTIVE: To investigate whether screening for carriership of sickle-cell
      anaemia and thalassaemia is desirable in the Netherlands, given the prevalence of
      the diseases, the possibilities of a screening test and the knowledge of the
      population at risk. DESIGN: Descriptive. SETTING: Wilhelmina Children's Hospital,
      Clinical Genetic Centre, Utrecht, the Netherlands. METHODS: In September 1992
      Dutch paediatricians were treating 128 children with sickle-cell anaemia and 31
      with thalassaemia major. Between October 1992 and December 1994, sickle-cell
      anaemia was diagnosed in 40 children and thalassaemia major in 14; of these, 16
      and 4, respectively, had been born in the Netherlands. A protocol for the
      screening for carriership adjusted to the Dutch situation was drawn up in the
      past, with an estimate of the corresponding costs. Patients with sickle-cell
      anaemia or thalassaemia major, their families, care givers and persons without
      disease but originating from Surinam, the Netherlands Antilles, Turkey or Morocco
      were interviewed about their knowledge of these two diseases. RESULTS: The
      knowledge of the diseases was low among the Turkish and Moroccan populations, and
      very global among the Surinamese and Antillian populations. There was more belief
      in supernatural causes than in a genetic predisposition. CONCLUSION: Given the
      low number of newly diagnosed haemoglobinopathies in children born in the
      Netherlands, the poor knowledge of the disease of the population at risk, the
      difficulty in identifying the best moment in life for screening and the rather
      complicated screening method, a screening programme for carriership of
      haemoglobinopathies in the Netherlands is not opportune. Where sickle-cell
      anaemia is concerned, screening for this disease during the neonatal period might
      be considered.

PMID- 9623204
TI  - [Differences between diabetes mellitus type 2 patients switched and not switched
      over to insulin treatment after specialist consultation].
AB  - OBJECTIVE: To describe the characteristics of patients with diabetes mellitus
      type 2 who were referred to an outpatient department for insulin therapy.
      SETTING: Hospital De Weezenlanden, Department of Internal Medicine, Zwolle, the
      Netherlands. DESIGN: Descriptive. METHOD: Referred patients with diabetes
      mellitus type 2 visited a diabetes team consisting of internist, diabetes
      specialist nurse, dietician, and ophthalmologist. After maximizing oral therapy
      according to the dosage scheme of the national guidelines of the Dutch College of
      General Practitioners, patients were switched over to insulin therapy if
      glycaemic regulation remained poor. After improvement and stabilisation of
      glucose values, patients were discharged to their general practitioners. Initial
      baseline characteristics of those who were switched over to insulin therapy
      within 6 months and those who were not were compared. RESULTS: Forty-eight men
      and 51 women were included. Mean age was 61.2 years (SD: 10.9) (range: 31-84)
      with a mean duration of diabetes of 8.9 years (SD: 8.3). Oral hypoglycaemic
      agents (OHA) had been used for 6.7 years (SD: 5.4). Mean glycohaemoglobin content
      was 10.4% (SD: 2.7) and 47 patients had hyperglycaemic complaints at baseline.
      Patients switched over to insulin within six months (n = 60; 61%) differed
      significantly from the non-insulin group (n = 38) in glycohaemoglobin (10.9% (SD:
      2.5) versus 9.6% (SD: 3.0)), duration OHA use (7.7 years (SD: 5.6) versus 5.0
      years (SD: 4.5)), and body mass index (26.5 kg/m2 (SD: 3.9) versus 29.1 kg/m2
      (SD: 5.6)). In women, only the body mass index was significantly different. Main
      reasons for not switching over to insulin were achieving acceptable control by
      optimizing OHA, education by diabetes specialist nurse and dietician, treatment
      of underlying disease or acceptable glycohaemoglobin percentage at baseline.
      Within six months 62 patients (63%) were discharged to their general
      practitioners. CONCLUSION: Referral to secondary care led to improved glycaemic
      control through maximizing oral therapy, education by the diabetes specialist
      nurse and dietician, switching over to insulin and diagnosis and treatment of
      underlying disease.

PMID- 9623205
TI  - [The development consultation for children in whom the physician suspects a
      developmental disorder: early experiences in Maastricht].
AB  - The so-called development consultation of the Heuvelland health care organization
      in Maastricht was organized with a view to early detection of developmental
      disorders in young children (< or = 6 years), thereby minimizing dysfunctioning.
      Health centre physicians, general practitioners and school doctors can refer
      children aged 0-6 years to this combined consultation hour of a paediatrician, a
      children's neurologist, a children's physiotherapist and in some cases, an
      educationalist and a speech therapist. After the starting-up phase, the number of
      referred children was three to six per month. The referring physician is usually
      present at the joint consultation after the examinations. At this meeting it is
      attempted to arrive at a diagnosis or at least to draw up a treatment plan. After
      the meeting, the child's parents or guardians are informed of the team's
      findings. The first group of 60 children included 9 with a cerebral paresis and
      18 with retarded motor development and speech retardation; 8 children were
      referred for exclusion of neurological/cerebral abnormalities.

PMID- 9623206
TI  - [Two children with unusual causes of torticollis: primitive neuroectodermal tumor
      and Grisel's syndrome].
AB  - Two children were presented with a torticollis. One, a 2-year-old girl, had a
      primitive neuroectodermal tumour of the cervical spinal cord which could not be
      radically removed surgically (the patient died three days later), the other, a 9
      year-old boy, had the syndrome of Grisel. He was treated with antibiotics, head
      traction and atlantoaxial posterior spondylodesis. Acquired torticollis is a
      frequent innocent symptom in children with cervical lymphadenopathy following a
      respiratory tract infection. These cases demonstrate that additional
      investigation should not be delayed if relief of symptoms is not achieved very
      soon.

PMID- 9623207
TI  - [Contact allergy to eyedrops containing beta-blockers].
AB  - In six patients (4 women aged 80, 62, 43 and 52 years and 2 men aged 58 and 51
      years), who used eyedrops containing beta-blockers for the treatment of glaucoma,
      allergic contact dermatitis of the eyelids was diagnosed. Three were allergic to
      metipranolol, 2 to levobunolol and 1 to timolol. In literature, less than 50
      cases of hypersensitivity to beta-blockers in eye medication have been reported.
      There are, however, reasons to assume that sensitization is more frequent: (a)
      not all patients are referred by the ophthalmologist to the dermatologist; (b)
      false-negative reactions to patch tests with the commercial preparations and with
      beta-blockers are not infrequent; (c) they are not routinely tested because beta
      blockers are difficult to obtain in pure form; (d) cross-reactions with other
      beta-blockers are infrequent, and changing to another preparation therefore
      usually solves the clinical problem. Nevertheless it is advisable to test a
      battery of beta-blockers (befunolol, levobunolol, metipranolol, timolol) in
      allergic patients. A test preparation of 2% in water or 3%-10% in petrolatum may
      be suitable. Control testing in non-exposed individuals is necessary to exclude
      irritation reactions.

PMID- 9623209
TI  - [The Montignac method: scientific foundation debatable].

PMID- 9623210
TI  - [The method of Montignac: scientific foundation debatable].

PMID- 9623211
TI  - [The method of Montignac: scientific foundation debatable].

PMID- 9623212
TI  - [The method of Montignac: scientific foundation debatable].

PMID- 9623213
TI  - [Old, short of breath and confused; delirium as a manifestation of pulmonary
      embolism in geriatric patients].

PMID- 9623214
TI  - [Old, short of breath and confused; delirium as a manifestation of pulmonary
      embolism in geriatric patients].

PMID- 9623215
TI  - [Old, short of breath and confused; delirium as a manifestation of pulmonary
      embolism in geriatric patients].

PMID- 9623216
TI  - [Old, short of breath and confused; delirium as a manifestation of pulmonary
      embolism in geriatric patients].

PMID- 9623217
TI  - [Cognitive and psychotic effects after cessation of chronic cannabis use].

PMID- 9623218
TI  - [Cognitive and psychotic effects after cessation of chronic cannabis use].

PMID- 9623219
TI  - [Clinical presentations mimicking acute myocardial infarction; therapeutic
      pitfalls].
AB  - Acute myocardial infarction remains one of the commonest causes of death. The
      pathogenesis is usually an occluding thrombus superimposed on a ruptured
      atherosclerotic plaque. However, several cardiac as well as non-cardiac diseases
      may give a presentation remarkably similar to acute myocardial infarction. Four
      patients are described, one woman aged 56 and three men aged 72, 63 and 60 years,
      who displayed the typical symptoms and ECG signs of acute myocardial infarction.
      The real conditions, however, were gallstones in two, a phaeochromocytoma in one
      and myocarditis in one. Two patients died, partly as the consequence of the
      failure to arrive at the correct diagnosis in time; the other two patients after
      adequate treatment were discharged in good condition.

PMID- 9623220
TI  - [Methylprednisolone in traumatic spinal cord injuries: not proven to be
      beneficial to the patient at the present time].
AB  - Ever since the publication in 1990 in The New England Journal of Medicine of a
      multicentre, randomised, double-blind, placebo-controlled trial on the efficacy
      of methylprednisolone (MP) in the treatment of acute, traumatic spinal cord
      injury, the advice is to administer MP as soon as possible to every patient
      presenting a traumatic spinal cord injury. This recommendation has been followed
      throughout the world, especially by traumatologists, and seems to be above
      criticism. However, the results of most cited studies, which have had a major
      influence on the treatment of patients with an acute, traumatic spinal cord
      lesion, show that the improvements in the neurological condition due to MP cannot
      be translated into a specific improvement in the functional status. Until it has
      been proven beyond reasonable doubt that MP can play a significant role in the
      treatment of these patients, we advise that MP should not be administered to a
      patient with acute, traumatic spinal cord injury, awaiting the results of more
      quantitative research. Such research is being performed by the Cochrane Brain and
      Spinal Cord Injury Group.

PMID- 9623221
TI  - [One hundred years of orthopedics in Netherlands. V. Arthroscopy].
AB  - Since the early eighties arthroscopy has become an important part of
      orthopaedics. Virtually every joint can be examined with an arthroscope. Apart
      from the diagnostic possibilities, an increasing number of arthroscopically
      guided surgical operations are possible. Knee arthroscopy can be used
      therapeutically for many conditions, including meniscal lesions, refractory
      synovitis, cruciate ligament lesions, tibial plateau fractures and osteochondral
      defects; in the shoulder it can be applied to lesions of the glenoid lip or the
      rotator cuff; in the ankle and foot, for osteochondral fractures and creation of
      an arthrodesis; in the wrist, for treatment of instability, intra-articular
      distal fractures of the radius and the carpal tunnel syndrome; in the hip, for
      removal of loose bodies and in the spine, for the performance of discectomy.
      Advantages over conventional open operations are smaller proportions of
      complications (< 2%), shorter hospital stay and more rapid rehabilitation. The
      areas of indication are defined in guidelines issued by the orthopaedic societies
      themselves; most orthopaedic surgeons follow these guidelines. A possibility for
      the future is use of laser in interventions on joints.

PMID- 9623222
TI  - [One hundred years of orthopedics in the Netherlands. VI. Surgical treatment of
      rheumatoid arthritis].
AB  - The prevalence of rheumatoid arthritis is about 1%. Loss of independence during
      daily activities is closely related to the multiple joint involvement of these
      patients. Also, chronic systemic autoimmune diseases and the extra-articular
      lesions cause considerable comorbidity. Goal of medical treatment is to reduce
      disease activity and local joint destruction. The surgical treatment consists of
      joint protective surgery and joint reconstructive surgery. The former procedure
      inhibits rapid progression of joint destruction by eradicating the bulk of
      synovial tissue. The latter procedure compensates for functional loss of an
      extremity by arthroplasties (both endoprostheses and arthrodeses) to increase the
      patient's independence. The perfect long-lasting functional prosthesis is
      available for some joints (hip and knee), but still in development for other
      joints (e.g. finger joints). In case of surgical reconstruction, a plan for
      possible complications (e.g. loosening) and their functional implications for the
      specific patient, should be part of the surgical indication policy. The outcome
      after a surgical procedure is closely related to preoperative patient factors
      (e.g. joint destruction) and the surgical expertise. Co-ordination of the
      treatment plan has to be done by the rheumatologist in close conjunction with the
      orthopedic/rheuma surgeon.

PMID- 9623223
TI  - [One hundred years of orthopedics in the Netherlands. VII. biomaterials].
AB  - The use of biomaterials in orthopaedics is becoming increasingly important. They
      are widely used in artificial joints, as bone replacement material and as
      resorbable material. Also (recombinant) bone morphogenetic proteins are used.
      Classification of biomaterials is based on composition (animal or human tissue,
      metals, polymers, ceramics or composites) or on biological reactions after
      implantation (bio-inert, bio-tolerant or bio-active). Depending on location and
      function biomaterials have to meet requirements with respect to durability
      (artificial joints), fixation (total hip prosthesis), flexibility (artificial
      ligaments), solubility (suture wire) and stiffness (plates and screws). The
      development of biomaterials is in full swing, focussing on the decrease of wear
      and the increase of durable fixation of artificial joints, and the induction of
      cells to form bone and cartilage tissue.

PMID- 9623224
TI  - [Clinical reasoning and decision making in the practice. A woman with abdominal
      complaints].
AB  - A female patient aged 28 years suffered from recurrent episodes of diarrhoea.
      Giardia lamblia was isolated once. By rigorous application of basic clinical
      skills, such as thorough history taking and physical examination, together with
      laboratory tests the correct diagnosis was established (in this patient systemic
      lupus erythematosus). Two important aspects of clinical reasoning, viz. returning
      to the patient when new information becomes available (cyclic way of working) and
      pattern recognition ensured a fruitful diagnostic process.

PMID- 9623225
TI  - [A standard method for reporting ramdomized medical scientific research; the
      'Consolidation of the standards of reporting trials' (CONSORT)].
AB  - The 'Consolidation of the standards of reporting trials' (CONSORT) statement was
      published in 1996. From that time on all manuscripts reporting randomized
      controlled trials (RCTs) submitted to JAMA, The Lancet or the British Medical
      Journal, must include a flow diagram and all the information in the CONSORT
      checklist. The Nederlands Tijdschrift voor Geneeskunde (Dutch Journal of
      Medicine) will follow suit. The manuscripts must be accompanied by this checklist
      together with the page numbers where each item may be found. The completed
      checklist will be sent to the editors and the reviewers but will not be
      published. This method of publication is also applicable to longitudinal or cross
      sectional studies. By making the process of publishing trials controllable it is
      hoped that the quality of these manuscripts will improve and with it their use
      and the quality of scientific research.

PMID- 9623226
TI  - [The Audioscope III in family practice: an instrument suitable for the diagnosis
      of hearing loss in comparison with the regular audiometer].
AB  - OBJECTIVE: To compare the results of hearing tests performed with the Audioscope
      III and the classical audiometer. DESIGN: Cross-sectional study. SETTING: Two
      general practices in South Limburg, the Netherlands. METHOD: The hearing of 115
      patients aged 55-93 years who visited the practice for any reason was tested with
      the Audioscope III and subsequently with the screening audiometer, in two silent
      examination rooms. The tests were performed independently by two general practice
      trainees. Finally, the subjects were asked which instrument they preferred. An
      ear was diagnosed as 'hard or hearing' if the Fletcher index measured with the
      audiometer was > 30 dB or if, with the Audioscope III, 1, 2, 3 or 4 tones were
      not heard at 40 dB. RESULTS: Depending on the number of tones not heard, the
      agreement between the measuring results ranged from 65 to 86%. If subjects during
      the examination with the Audioscope III failed to hear > or = 2 tones at 40 dB,
      the conclusion 'hardness of hearing', judged by the audiometric results, was
      correct in all cases. Conversely, the proportion of ears incorrectly diagnosed as
      'not abnormal' at this limit was 39%. Hearing tests with the Audioscope III took
      little time (0.5-4 minutes) and were in general tolerated well. CONCLUSION: The
      Audioscope III is a useful instrument in situations in which there is a high
      prevalence of auditory disorders, for instance in general practices with a
      relatively elderly patient population.

PMID- 9623227
TI  - [The screening for asymptomatic vascular disease and risk factors in high risk
      patients: current practice].
AB  - OBJECTIVE: To assess current practice in screening for asymptomatic vascular
      disease and risk factors in patients referred with vascular disease or
      cardiovascular risk factors. DESIGN: Descriptive, retrospective. SETTING:
      University Hospital Utrecht, Utrecht, the Netherlands. METHOD: By means of the
      computerized hospital registration system all patients who were referred to the
      outpatient clinic with carotid stenosis, peripheral artery disease, abdominal
      aortic aneurysm, diabetes mellitus, hyperlipidaemia or hypertension during one
      year were identified. By means of the same hospital registration system the
      frequency of diagnostic tests performed to detect atherosclerosis or risk factors
      in these patients within a period of 5 months round the first attendance was
      determined. RESULTS: 372 Patients with a vascular disease and 317 patients with a
      risk factor were identified. Tests to detect carotid stenosis, peripheral artery
      disease or an abdominal aortic aneurysm were each performed in less then 6% of
      all patients except the test for abdominal aortic aneurysm. Tests to detect
      coronary artery disease were performed in about 50% of all patients. Tests to
      detect diabetes mellitus were performed in 35% of the patients with vascular
      disease and in 81% of the patients presenting with hyperlipidaemia or
      hypertension. Tests to detect hyperlipidaemia were performed in 18% of the
      patients with a vascular disease and in 76% of the patients with diabetes or
      hypertension. CONCLUSION: The results of this study suggest that in current
      practice patients referred for vascular disease or cardiovascular risk factors
      are infrequently screened for asymptomatic macrovascular disease and risk
      factors.

PMID- 9623228
TI  - [Association between the intima-media thickness of the common carotid and
      subsequent cardiovascular events in subjects, 55 years and older, in the
      Rotterdam study (ERGO)].
AB  - OBJECTIVE: To determine whether common carotid artery intima-media thickness
      (IMT) is related to future cardiovascular disease. DESIGN: Nested case control
      study. SETTING: The suburb of Ommoord in Rotterdam, the Netherlands. METHOD: As
      part of the Rotterdam study among 7983 subjects aged 55 years and over,
      ultrasound images of the common carotid artery were stored on videotape of 5965
      subjects at baseline (1990-1993). Analysis (logistic regression) was based on 190
      cases of cardiovascular disease (myocardial infarction and stroke), registered up
      to December 31, 1994. IMT was measured from videotape for all cases and a control
      sample of 1373 subjects who remained free from myocardial infarction and stroke
      during follow-up. The mean duration of follow-up was 2.7 years. RESULTS: The age
      and sex adjusted cardiovascular disease risk increased by 45% (95% confidence
      interval (95% CI): 25-69) per standard deviation increase (0.163 mm) in IMT.
      Stroke risk increased by 45% (95% CI: 25-69) per standard deviation increase and
      the risk of myocardial infarction increased by 43% (95% CI: 16-78). Additional
      adjustment for several cardiovascular risk factors attenuated the association.
      CONCLUSION: Increased common carotid intima-media thickness was associated with
      subsequent cardiovascular events. These results support the use of carotid intima
      media thickness measurements as a surrogate endpoint in observation and
      intervention studies. The value of IMT measurements for individual patients and
      cardiovascular screening merits further study.

PMID- 9623229
TI  - [Myocardial infarct in the puerperium].
AB  - Two women of 34 and 31 years suffered an acute myocardial infarction in the
      puerperium. One of them had many risk factors for atherosclerosis:
      hypercholesterolaemia, hypertriglyceridaemia, diabetes mellitus, hypertension,
      obesity, nicotine abuse and a positive family history for cardiovascular disease.
      She had an occluded right coronary artery and was successfully treated with
      percutaneous transluminal coronary angioplasty. The other patient had an acute
      myocardial infarction after her first delivery. She was known with
      hypercholesterolaemia, obesity and nicotine abuse. During her latest pregnancy
      she was treated with acetylsalicylic acid. Again she developed an acute
      myocardial infarction in the puerperium, probably due to coronary dissection.
      Although the incidence of acute myocardial infarction is low in the peripartal
      period (less than 1 in 10,000) the diagnosis should be considered when a woman
      presents with chest pain or dyspnoea.

PMID- 9623230
TI  - [Invasive streptococcal infection as a complication of chickenpox].
AB  - Two girls aged 11 months and 6 years, presented with an invasive group A
      streptococcal (GAS) infection during the course of primary varicella. The infant
      had severe cellulitis of the left arm and leg, fever and bacteraemia. She
      developed osteomyelitis of ulna and tibia. The 6-year-old girl had a fever > 38.5
      degrees C, hypotension, an acute respiratory distress syndrome, liver function
      abnormalities, and positive cultures of blood and joints. Her clinical picture
      was compatible with a GAS-associated toxic shock syndrome. If during the course
      of primary varicella persistent fever, secondary fever or pain in one or more
      extremities occurs, invasive bacterial infection by GAS or Staphylococcus aureus
      should be considered, even in the absence of skin infection or cellulitis.

PMID- 9623231
TI  - [Iodine-125 implantation in localized cancer of the prostate; too early for
      rejoicing].
AB  - The role of I-125 implantation in treatment with curative intent of carcinoma of
      the prostate is not yet perfectly clear. No long-term results in large groups of
      patients have so far been published. An inherent restriction of the technique is
      that it is difficult to attain a high dose of radiation in the periphery of the
      prostate. Consequently, the technique appears to be less or not appropriate for
      peripherally located tumours or tumours with extracapsular spread. Implantation
      of I-125 should for the moment be regarded as an experimental therapy. Its
      application should be limited to strictly selected patients and should be carried
      out as a part of trials.

PMID- 9623232
TI  - [One hundred years of orthopedics in the Netherlands. VIII. Pediatric
      orthopedics].
AB  - Orthopaedic disorders in children differ in type from those in adults: most
      frequent are congenital anomalies and disorders of growth and development. The
      special nature and relative rarity of these conditions justify the separate
      development of this branch of the discipline. Fractures almost always heal
      normally after closed reduction and immobilization in a plaster cast; fractures
      close to epiphyseal discs and in joints require special attention. Slipping of
      the upper femoral epiphysis necessitates surgical fixation of the epiphysis.
      Benign bone tumours occur relatively often and mostly require no surgical
      intervention. The prognosis of solid malignant bone tumours has improved since
      the introduction of (neo)adjuvant chemotherapy and limb-sparing surgery. In case
      of difference in leg length, the length of both legs is predicted with the aid of
      roentgenological measurements. Inhibition of the growth of the longer leg gives
      rise to fewer complications than lengthening of the short leg. The essence of the
      treatment of growth disorders due to abnormal ossification of the cartilage is to
      monitor the natural repair process and to intervene if permanent malformation
      threatens.

PMID- 9623233
TI  - [One hundred years of orthopedics in the Netherlands. IX. The treatment of
      chronic osteomyelitis].
AB  - Chronic osteomyelitis is characterized by cicatrization of the focus of infection
      with deteriorating vascularization, which makes the disease increasingly
      difficult to treat. The treatment in chronic osteomyelitis consists primarily in
      surgical debridement of the scarified focus of infection; stabilization with
      external fixation allows better treatment. Following debridement, local
      antibiotic treatment is possible with gentamicin containing cement beads, if
      necessary combined with systemic antibiotic treatment. If the infection heals
      well, a reconstruction may, if necessary, be carried out: bone defects frequently
      necessitate bone transplantation, bone segment shifting (Ilizarov method) or free
      muscle flap grafts. In the future, resistant bacteria will make healing harder.
      There will be more possibility to use resorbable antibiotic vehicles and bone
      replacing biomaterials.

PMID- 9623234
TI  - [One hundred years of orthopedics in the Netherlands. X. Sports injuries].
AB  - Sports injuries result from frequently repeated similar movements performed with
      submaximal force. In practice the term is also used, incorrectly, for many other
      injuries sustained during, or even outside, the practising of sports. Running may
      lead to injuries of muscles (rupture, chronic compartment syndrome), of tendons
      (peritendinitis, tendinosis, partial rupture, insertion tendinitis), of bone
      (stress fracture) and of cartilage (athrosis). Jumping mostly puts the ankle at
      risk, especially of development of an anterior or posterior impingement syndrome.
      Throwing puts much strain on the shoulder muscles; possible problems are
      microruptures in the rotator cuff, avulsion of the glenoid rim, chronic
      tendinitis of the biceps tendon and entrapment of the suprascapular nerve. The
      main element of the treatment is rest. If symptoms persist, surgery may be
      considered. Previous diagnostic imaging may then be of value.

PMID- 9623235
TI  - [Clinical thinking and decision-making in practice. A nurse with low back pain
      radiating to both legs].
AB  - A 50-year-old nurse with chronic back pain developed painful paraesthesia in the
      legs and saddle region during walking. Because pain in the legs could not be
      provoked by standing erect, the orthotic-lordotic cauda syndrome or neurogenic
      intermittent claudication (spinal canal stenosis) became unlikely and vascular
      intermittent claudication likely. The femoral pulses were absent. Angiography
      showed severe stenosis of the distal aorta which was successfully treated by
      percutaneous transluminal angioplasty.

PMID- 9623236
TI  - [The relationship between the serum level of prostate specific antigen and bone
      and CT scans in the staging of the primary carcinoma of the prostate].
AB  - OBJECTIVE: To determine the relationship between the serum level of prostate
      specific antigen (PSA) and the presence of abnormalities in a skeletal or CT scan
      in patients with primary carcinoma of the prostate. DESIGN: Retrospective.
      SETTING: Academic Medical Centre, Amsterdam. PATIENTS AND METHODS: The serum PSA
      levels were compared with the findings in the skeletal and CT scans of 440
      patients with carcinoma of the prostate without clinical signs of metastases,
      seen in the period from January 1990 to December 1994 in the outpatient clinics
      for Urology of the Academic Medical Centre (AMC) in Amsterdam, Hospital Gooi
      Noord in Blaricum and Hospital De Heel in Zaandam. CT scan data were analysed
      only from the AMC and Hospital Gooi-Noord. RESULTS: There were 76 patients with a
      positive bone scan (17.3%) and 31 (out of 337; 9.2%) with a positive CT scan.
      Higher PSA serum levels went together with increasing risk of abnormalities in
      bone or CT scan. Of 85 patients with PSA values < 10 micrograms/l, none had a
      positive bone scan and one (out of 73; 1%) a positive CT scan; of the 180
      patients with PSA levels < 20 micrograms/l, 4 (2.2%) had a positive bone scan and
      2 (out of 154; 1.3%) a positive CT scan. The T stage, the histological grading
      and the serum alkaline phosphatase activity appeared not to have any
      supplementary value. CONCLUSION: In view of the low frequency of abnormalities in
      a bone or CT scan in patients with low PSA levels, it appears justified no longer
      to recommend bone or CT scanning for staging of patients for a clinically non
      metastasized carcinoma of the prostate and serum PSA levels < 20 micrograms/l.

PMID- 9623237
TI  - [Iodine-125 implantation in localized prostate cancer; technique and results from
      100 patients at the Academic Hospital, Utrecht].
AB  - OBJECTIVE: To evaluate the preliminary results of perineal implantation of I-125
      seeds in patients with cancer of the prostate. DESIGN: Prospective descriptive
      cohort study. SETTING: Utrecht University Hospital, the Netherlands. METHODS: In
      the period from October 1989 to December 1996, a total of 149 patients with
      localized carcinoma of the prostate were treated with perineal implantation of I
      125 seeds. One hundred of them could be evaluated. Results regarding progression
      and complications were collected prospectively. RESULTS: The median follow-up was
      3 years (range 12-74 months). Progression of the disease was observed in 28
      patients: local in eight, distant in four and both local and distant in one; 15
      patients only showed a rise of prostate specific antigen level, without further
      symptoms. Fourteen patients were given supplementary treatment. No major
      complications were seen; four patients had persistent micturition problems and
      three, intestinal problems. CONCLUSION: Perineal I-125 implantation causes few
      complications and may constitute an alternative to external irradiation as well
      as to radical prostatectomy in the treatment of localized carcinoma of the
      prostate.

PMID- 9623238
TI  - [The quality of life after stem cell transplantation: problems with fatigue,
      sexuality, finances and employment].
AB  - OBJECTIVE: To determine the quality of life in patients after high dose
      chemo/radiotherapy followed by bone marrow stem cell transplantation for the
      treatment of a malignancy. DESIGN: Structured questionnaire and in-depth
      interview. SETTING: Academic Hospital Maastricht, the Netherlands. METHODS: All
      patients who had undergone stem cell transplantation (SCT) at least 6 months
      previously (n = 54) were asked to participate in an analysis of their quality of
      life using the 'Quality of life questionnaire' (QLQ-C30) developed by the
      European Organization for Research and Treatment of Cancer (EORTC) and an in
      depth interview. RESULTS: The EORTC QLQ-C30 was answered by 52 (96%) of the
      patients and 46 (85%) participated in the interview. The patients were divided in
      cohorts of 6-24 (n = 16), 25-48 (n = 22) and more than 48 months (n = 14) after
      SCT. Quality of life was 73.9 on a 100 per cent scale. There were no significant
      differences between various cohorts after SCT. However, patients transplanted
      more than 4 years before had significantly more complaints of nausea and
      vomiting. The structured interview revealed significant problems with fatigue,
      sexuality, finances and return to work. No clear relation with time elapsed after
      transplantation was found. CONCLUSION: SCT has a significant impact on several
      quality of life issues, which should be considered in the application of this
      modality in palliative situations. The EORTC QLQ-C30 may be helpful to analyse
      overall quality of life after transplantation, but provides no information on
      individual effects on quality of life.

PMID- 9623239
TI  - [Hypertension with neurologic manifestations caused by an enlarged prostate].
AB  - A 74-year-old man suffering from hypertension had transient loss of strength in
      his left arm and leg. His severe hypertensive spells were caused by high-pressure
      chronic bladder retention. The patient had benign hyperplasia of the prostate for
      which transvesical enucleation was performed. The blood pressure then returned to
      normal. The transient neurological deficits had probably been caused by the
      abrupt blood pressure changes. In older male patients the possibility of this
      reversible cause of hypertension should be kept in mind.

PMID- 9623240
TI  - [Russia: sex, drugs, AIDS and the Doctors Without Borders].
AB  - Russia faces a serious crisis and finds it difficult to look after all its
      citizens. Alcoholics, homeless and elderly fight to survive. A recent problem is
      the rapid increase in the number of injecting drug users. In Moscow an estimated
      100,000 users form an important core group for HIV transmission. With the health
      system collapsed and sexually transmitted diseases on the rise, all ingredients
      for a HIV epidemic are present. By the turn of the century the Ministry of Health
      forecasts 800,000 HIV positives. Medecins sans Frontieres in co-operation with
      the government started a HIV prevention campaign.

PMID- 9623241
TI  - [Fast-acting insulin analogs].

PMID- 9623242
TI  - [Preoperative diagnostic stereotaxic biopsy is a good predictor of breast cancer
      in patients with mammographic findings indicating a possible malignancy].

PMID- 9623243
TI  - [Preoperative diagnostic stereotaxic biopsy a good predictor of breast cancer in
      patients with mammographic findings indicating a possible malignancy].

PMID- 9623244
TI  - [The efficacy of manipulation therapy in low back pain: no definitive answers
      from systematic reviews of the literature and clinical guidelines].

PMID- 9623245
TI  - [Localized corticosteroid injections for the 'trigger finger': good short-term
      results, but with a great likelihood of recurrence].

PMID- 9623247
TI  - [Environmental factors possibly associated with onset of senile dementia].
AB  - Factors associated with senile dementia have not been clarified, and factors,
      especially those in the living environment which seem to have a close link to the
      dementia need to be analysed. We conducted a case-control study targeting
      patients within the jurisdiction of Nagahama Public Health Center in Shiga and
      Hikone city, who are diagnosed to have senile dementia of the Vascular type,
      senile dementia of the Alzheimer type, and senile dementia of the Mixed type, and
      compared them to age matched controls. The outcome of the study by Matched pair
      analysis (McNemar's test) before the onset of the senile dementia were as
      follows. 1 The factors related to senile dementia of the vascular type were:
      Previous histories (Matched Odds Ratio (MOR): 8.0 p < 0.05), disturbance of the
      lower limbs (MOR = 8.0 p < 0.05). Environmental factors were: strong preference
      for sweets (MOR = 8.0 p < 0.05 female), smoking (MOR = 3.7 p < 0.10), lower
      utilization of health care (MOR = 3.3 p < 0.10), such as periodic medical check
      (MOR = 0/6 p < 0.10), sleep (MOR = 0/5 p < 0.10), less commitment to hobbies (MOR
      = 2.6 p < 0.10), such as handicrafts (MOR = 0/5 p < 0.10) etc, less intercourse
      with relatives (MOR = 0/9 p < 0.01), not living together with children's family
      (MOR = 0.20 p < 0.05 female), and death (MOR = 8/0 p < 0.05) or hospitalization
      (MOR = 9.0 p < 0.05) of a family member. 2 The factors related to senile dementia
      of the Alzheimer type and the Mixed type were: some previous histories (MOR = 8.0
      p < 0.05), less disturbance of gait (MOR = 0/5 p < 0.10). Environmental factors
      were: lower utilization of health care, such as periodic medical check (MOR =
      0.18 p < 0.05), and lower participation in exercise (MOR = 0/5 p < 0.10) etc,
      less association with neighbors (MOR = 0.11 p < 0.05), less participation in
      community activities (MOR = 0.11 p < 0.05), not living together with children's
      family (MOR = 0/8 p < 0.05), relocation (MOR = 5/0 p < 0.10) and retirement (MOR
      = 5/0 p < 0.10).

PMID- 9623246
TI  - [Virological evaluation of the treatment of HIV-infected patients with
      (combinations of) antiretroviral agents in the Academic Medical Center of
      Amsterdam].

PMID- 9623248
TI  - [Vitamin A, B1 and C status of elderly living alone].
AB  - A cross-sectional survey was performed to examine the vitamin A, B1 and C status
      and relating factors among the elderly aged over 65 years and living alone in the
      western parts of Hachioji, Tokyo. Of 159 subjects, 17 men and 81 women
      participated in this survey. A questionnaire and interview on the socioeconomic
      conditions, state of health and life-style and easting habits, and a medical
      examination were conducted and blood collected and analyzed. Vitamin A, B1 and C
      status was evaluated on the basis of serum vitamin A concentration, whole blood
      vitamin B1 concentration and serum vitamin C concentration, respectively. Most of
      the participants were those who were comparatively active in daily life. Thirty
      three percent of the participants were assessed to be in poor vitamin B1 status,
      while 1% and 4% were assessed to be in poor vitamin A and C status, respectively.
      Significant correlations were found between whole blood vitamin B1 and serum
      vitamin A concentrations and between whole blood vitamin B1 and serum vitamin C
      concentrations. About 10% of the participants had blood vitamin B1 concentrations
      as below 35 ng/ml and at the same time, significantly lower serum vitamin A and C
      concentrations than others. Thus, inadequate nutrient intakes or inappropriate
      diet intakes were suggested as a cause. While good vitamin status was linked with
      use of vitamin preparations or vitamin supplements, lowered vitamin status was
      found to be closely associated with such dietary practices or behavior as dietary
      indifference to food combinations, a higher preference of rice as the staple food
      and having a reported difficulty in preparing meals.

PMID- 9623249
TI  - [Factors affecting three elements of the medical expense for the aged].
AB  - The per capita medical expense was studied for inpatients and outpatients aged 70
      years and over under the National health insurance for fiscal year 1990 among 678
      cities in Japan. Per capita medical expense consists of three factors, i.e.
      service-acceptance rate, bed-days per receipt and the medical expense per day. To
      clarify what factors are associated with these three factors of the medical
      expense, multiple regression analyses were performed using several indices of
      medical supply and medical need, family type, health projects and socioeconomics.
      The results are as follows. (1) The major factor that was correlated
      significantly and positively with the expense and service-acceptance rate for
      inpatients was medical supply. (2) Both the bed-days receipt and the service
      acceptance rate for inpatients were negatively correlated with cerebral apoplexy.
      (3) Medical expenses per day for inpatients and outpatients were negatively
      correlated with medical supply, such as the number of hospitals per population.
      (4) The major factor that was correlated positively with medical expenses for
      outpatients was medical need, such as cancer and heart disease. (5) Service
      acceptance rate of outpatients was correlated positively with the factors of
      accessibility, such as number of medical institutions per area. (6) Days per
      receipt of outpatients was correlated negatively with the level of health among
      cities.

PMID- 9623250
TI  - [Utilization of information concerning home welfare services for the elderly and
      degree of satisfaction].
AB  - A model was used to clarify the causal relationship between variables concerning
      utilization and degree of satisfaction towards information related to home
      welfare services for the elderly in order to obtain a guideline to assist in
      future provision of information concerning home welfare services. Subjects were
      selected by stratified random sampling from 2,200 elderly people (over 65 years
      old) in five districts of Hokkaido. Valid responses were obtained from 1,536
      people (mean age: 72.1 years; gender composition: 58.2% men, 41.8% women). The
      items of the survey were: gender, age, educational background, family
      composition, income, health status (self-rated health, history of treatment at
      medical institutions), needs concerning information on home welfare services for
      the elderly, and degree of satisfaction with availability of information outlets
      and information services. The results of path analysis showed that: 1) the
      tertiary factors of age, educational background and income affect the secondary
      factor of needs concerning information on home welfare services for the elderly,
      2) this secondary factor controls the primary factor of mass and personal media,
      and 3) the way of obtaining information affects the degree of satisfaction
      towards the information.

PMID- 9623251
TI  - [Ethical issues regarding individual data collection and utilization in community
      health care programs].
AB  - To understand the nature of ethical issues in community-based health care
      programs, we conducted a mail survey of subjects who were public health nurses
      employed by municipal governments. The questionnaire consisted of questions about
      data collection, usage, disclosure, and educational experience. In 1996 we
      received 536 completed questionnaires which were then analyzed. Regarding who
      should input data into computers, the number of those who considered that
      municipal offices other than public health nurses would be the most appropriate
      for the input of examination data was the largest, followed by those who felt
      that contracting out was best. Many of the public health nurses considered that
      they needed to obtain informed consent for collection, usage and disclosure of
      sensitive items, such as data on HIV infection. The number of those considering
      that they could not disclose results of examinations to other community-based
      specialists in health and welfare without the subject's agreement was very high.
      In health examination programs, the public health nurses requested information on
      date of birth and occupations, but there was some hesitation in requesting the
      latter information. Although about a half of subjects responded that they did not
      require data concerning the first sexual intercourse in cervical cancer
      screening, 90 percent asked breast feeding history in breast cancer screening.
      Approximately 90 percent gave results of the examination to participants
      personally through personal communication or mail. Of the respondents, 40 percent
      reported having had educational courses on ethics while the others did not. There
      were some responses that reminded us of the unsatisfactory level of understanding
      about ethical issues, which underlined the need to emphasize importance, of
      including this in educational curricula.

PMID- 9623252
TI  - [AIDS and STD knowledge and risk behaviors among commercial sex workers in
      Myitkyina, Myanmar].
AB  - This study investigated AIDS and STD (Sexually Transmitted Diseases) knowledge,
      risk behaviors, and condom use among two different groups of female commercial
      sex workers (CSWs) in Myitkyina, Myanmar. Individual in-depth interviews were
      conducted with 65 direct and 65 indirect CSWs. These CSW groups differ in the
      prices they charge, their places and modes of employment, levels of knowledge
      concerning HIV and STD transmission and prevention, number of clients served,
      levels of condom use and STD symptoms. Indirect CSWs have higher levels of
      knowledge, fewer partners, and more frequent condom use; but still have high
      levels of STD symptoms and frequently engage in unprotected sex with clients.
      Many CSWs and their clients were originally from other regions; these people
      could well be agents in the rapid spread of the HIV virus throughout Myanmar.
      Interventions targeted to specific groups of CSWs and clients should be
      undertaken as soon as possible, including educational activities concerning AIDS
      and STD transmission and prevention, condom promotion and distribution, and
      activities to improve the health sector's capabilities to help both CSWs and
      their clients.

PMID- 9623253
TI  - [Simulation exercises, a problem oriented method of learning public health in
      medical education].
AB  - Using the case method of learning of American business schools, we introduced
      "Simulation Exercises (SE)," a problem oriented method of public health education
      for medical students. With SE, a group of students were given simulated cases of
      patients or situations (SC), and were asked to assume the role of physicians or
      other public health workers using their skills and knowledge of public health.
      Students learn on their own, with the aid of tutors, through discussion, role
      play, investigation of literature, and a small field survey. There have been a
      whole variety of SC covering most of the current topics in public health ranging
      from mental health, dental health, industrial health, maternal & child health,
      elderly care, terminal care and international health. Each SC has 5 to 10
      questions which stimulate and direct the students' group discussion. Some of the
      questions do not have a correct answer, but the criteria used to evaluate the
      students included clarity, consistency, and comprehensiveness of their ideas in
      addition to the positive commitment to the group discussion. At the end of the
      week-long group learning, each group demonstrated the results of their
      discussion. Role play was often used to demonstrate what they learned. As a
      result, students participated positively and concentrated and enjoyed the
      learning exercise very much. An anonymous survey shortly after SE showed that
      more than 80% of students felt a positive change in their rating of public health
      among the many subjects of study. Tutors also changed their rating of the
      students after observing their positive attitude and sometimes very creative
      ideas. In conclusion, we found SE to be useful for practical learning by medical
      students of public health.

PMID- 9623254
TI  - [Health promotion service adopting dumbbell exercise in Shirataka town, Yamagata-
      examination on body fat, lean body mass and serum lipids in middle-aged obese
      subjects].

PMID- 9623255
TI  - [Etiology of contact lens failure in pediatric aphakia. Indications for
      intraocular lenses?].
AB  - Due to the low rate of complications, lentectomy and contact lens fitting is the
      standard treatment for congenital cataract. However, contact lens fitting is not
      possible in all children. The authors report the main reasons for discontinuation
      of contact lenses in their patients. METHOD: In 134 consecutive lentectomies of
      90 children, the underlying eye diseases and general diseases, the age at
      operation, compliance of parents and children, and social background were
      analyzed. RESULTS: Twenty of the 90 children had to discontinue contact lens
      wearing. Twelve of these children were operated on one eye and 8 on both eyes.
      Only 2 children showed signs of contact lens complications. In 2 children
      treatment was stopped because of the poor visual prognosis and in 10 children the
      parents discontinued contact lens treatment because of a severe handicap of the
      child (n = 2) or due to misunderstanding and parental noncompliance (n = 8). Six
      children refused contact lenses without obvious reasons. Among the latter,
      children 2-4 years of age were at the greatest risk. Children with additional
      systemic abnormalities frequently developed contact lens intolerance. CONCLUSION:
      In children with systemic abnormalities and in the case of parental communication
      and compliance problems, discontinuation of contact lenses has to be expected in
      up to 30% of cases. In these children and in children who object to contact
      lenses at the age of 2-4 years, intraocular lens implantation should be
      considered, especially in unilateral cataract, if successful contact lens
      treatment is not achievable within 8-12 weeks.

PMID- 9623256
TI  - [Inflammatory reaction of the anterior eye segment. Cataract extraction in
      patients with and without diabetes mellitus].
AB  - BACKGROUND: We attempted to illustrate connections between selected metabolic
      parameters and the inflammation course in patients after cataract operations.
      PATIENTS AND METHODS: A prospective study comprised 64 patients aged between 35
      and 88, 41 of them non-diabetics (group I) and 23 type II diabetics (group II).
      The following blood parameters (patients with an empty stomach) were selected for
      the study: cholesterol (chol), triglycerides (tri), HDL and LDL cholesterol,
      blood sugar (BZ), glycolized hemoglobin (HbA 1c) and C-reactive protein (CRP). To
      assess the course of the inflammation in the anterior chamber of the eye by
      objective criteria, tyndallometric measurement was used. The changes in the
      cornea were measured pachymetrically. The investigations were done the day before
      the operation and the first to third post-operative days. RESULTS: CRP was
      significantly different only in the males in both groups (p = 0.011). No
      significant differences were measured between the two groups for the blood
      parameters chol, tri and HDL- and LDL cholesterol. Tyndallometric measurements
      showed highly significantly increased anterior chamber reaction in the diabetic
      group (p = 0.0018). A comparison within the diabetic group did not show any
      significant differences between patients with or without retinopathy (p = 0.48).
      Comparison of diabetic patients without retinopathy with non-diabetic patients
      showed a clearly significant difference (p = 0.014) for this parameter. No
      significant pachymetric difference was found between the two groups (p = 0.49).
      CONCLUSIONS: The disruption in the blood-aqueous barrier and the clinical
      inflammatory reaction to the cataract operation are stronger in type II diabetics
      than in non-diabetic patients, especially in the presence of
      microangioorganopathy.

PMID- 9623257
TI  - [Cataract operation after silicone oil surgery. Oil drop adhesion to silicone
      lenses].
AB  - PURPOSE: To investigate the phenomenon of oil droplet formation on silicone IOLs
      with regard to visual acuity, intraocular pressure (i.o.p.), and clinical
      findings. PATIENTS AND METHODS: Retrospective study (january 1995 to December
      1996) on 78 patients who underwent cataract surgery after previous complex
      silicone oil surgery for PVR-complicated rhegmatogenous retinal detachments (64)
      or proliferative diabetic retinopathy (14). Follow-up after cataract surgery 15.5
      (7.55) months. PMMA IOLs were used in 50 and silicone IOLs in 19 cases. Nine
      patients did not receive an intraocular lens. The groups were divided up further
      with regard to secondary YAG capsulotomies and oil explanations. Before cataract
      operation, one or two (1, 23) complex vitreoretinal operations were performed
      with case-dependent additional retinal laser coagulations. For statistical
      analysis the two-sided t-test and/or Welch's test were applied. RESULTS: The
      preoperative mean visual acuity (VA) was significantly better (P < 0.0001) in the
      group treated with PMMA IOLs than in the one without IOL (VA with PMMA 0.093,
      silicion 0.075, without IOL 0.026). Significant improvement of VA after surgery
      was found with PMMA Implantation after YAG capsulotomy without silicone oil
      explantation (P = 0.0003). Visual improvement was best in PMMA IOLs after YAG
      capsulotomy with the remaining silicone oil (0.076), followed by the group
      without IOL implantation (0.063). In the groups with PMMA IOLs/YAG/oil
      explantation, a rise in VA of 0.06 was achieved, and in silicone IOLs/YAG/oil
      explantation, the rise in VA was 0.002. No statistically significant differences
      were found in postoperative mean VA. Preoperative intraocular pressure (i.o.p.)
      was lower in the PMMA group than in the group without IOL (P = 0.0447). No
      significant differences in the postoperative IOPs were found between groups, but
      in the PMMA/YAG/oil in situ group, IOP decreased significantly after surgery (P =
      0.0142). Maculopathies were found in the PMMA group in 31, in the silicone group
      in 16, and in the group without IOL implantation in 7 cases. Optic atrophy was
      found in the PMMA group in 8, in the silicone group in 4, and in the group
      without IOL implantation in 3 cases. CONCLUSIONS: In all groups silicone oil
      surgery and secondary cataract operation with or without YAG capsulotomy and oil
      explantation achieved stable or slightly improved mean VA with significance in
      PMMA IOL implantation/YAG capsulotomy without oil explantation. Comparing PMMA
      IOLs/YAG/oil explantation and silicone/YAG/oil explantation, an advantage in the
      PMMA groups was found. However, because of large interindividual differences
      (large standard deviations) there was no statistical significance. Thus, in this
      series the phenomenon of silicone droplet adhesion on silicone IOLs is secondary
      to the influence of retinal pathologies.

PMID- 9623258
TI  - [Duplex ultrasound examinations of retinal circulation after inhalation of
      various mixed respiratory gases].
AB  - BACKGROUND: Hyperoxic-hypercapnic inhalation is a therapeutic option in vascular
      disorders of the retina. The effect of hyperoxic and/or hypercapnic inhalation on
      the perfusion of the retina was examined. METHODS: Twenty-five young adults
      between 18 and 35 years were investigated in a prospective study. They inhaled
      one of three different mixtures of breathing gases: (1) 100% O2, (2) Carbogen 240
      (95% O2 and 5% CO2), (3) 92% O2 with 8% CO2 and were examined by color Doppler
      imaging of the CRA and OA before and after inhalation. The resistance index (RI)
      was calculated. RESULTS: The majority of the subjects showed an Increase in the
      RI in both ophthalmic vessels after inhalation of pure O2, a decrease after
      breathing in 92% O2 and 8% CO2 and it remained almost constant with inhalation of
      95% O2 and 5% CO2. CONCLUSIONS: Inhalation of 92% O2 and 8% CO2 is a possibility
      for decreasing the peripheral resistance of OA and CRA. No change in blood flow
      was observed with Carbogen 240.

PMID- 9623259
TI  - [Intraocular pseudotumor in an AIDS patient. Block excision, differential
      diagnosis, histology].
AB  - BACKGROUND: Intraocular pseudotumors are a rare event in Aids patients and often
      pose diagnostic problems. CASE REPORT: A 37-year-old patient who had had HIV
      seroconversion for 7 years was seen to developed progressively growing, multiple,
      disseminated, subretinal lesions OD > OS, accompanied by exudative retinal
      detachment and iritis. Since all etiological laboratory diagnostic efforts to
      detect an infectious, noninfectious and neoplastic systemic lesion failed, a
      diagnostic and curative therapeutic chorioretinal excisional biopsy specimen of
      the largest of the tumors (3 x 3 x 2 mm) was taken. The histological work-up
      demonstrated granulation tissue similar to an intraocular pseudotumor without
      signs of infection, malignancy or reactive lymphoid hyperplasia. This finding
      resulted in systemic corticosteroid treatment with complete resolution of the
      lesions in both eyes and no recurrences. CONCLUSIONS: An invasive diagnostic
      procedure in patients suffering from lesions of unknown cause resulting in the
      institution of an appropriate medical treatment may be beneficial for the
      integrity and vision of the respective eye.

PMID- 9623260
TI  - [Familial juvenile macular dystrophy with congenital hypotrichosis capitis].
AB  - BACKGROUND: Our knowledge about the pathogenesis of hereditary macular diseases
      is still very circumscript. For genetic determination, a knowledge of the
      coincidence of eye symptoms and other defined common symptoms is helpful. The
      purpose of this paper was to present two sisters of a family of consanguineous
      parents with the combination of hypotrichosis of the head and macular dystrophy
      in the context of a tricho-ocular malformation of an ectodermal dysplasia. A
      review of the recent literature is included. PATIENTS AND METHODS: Two 13- and 17
      year-old sisters presented at our hospital with reduced visual acuity because of
      symmetrical central changes of the retinal pigment epithelium and chorioatrophic
      scars according to macular dystrophy combined with hypotrichosis capitis. We
      performed fundus perimetry and histological examinations of the hair. RESULTS:
      The 13-year-old patient exhibited central changes of the retinal pigment
      epithelium leading to a relative central scotoma for Goldmann 1/4 during fundus
      perimetry in both eyes (visual acuity 0.125 and 0.4). We found central
      chorioatrophic scars, followed by absolute central scotomas, with unstable
      fixation in the upper retinal hemisphere in her 17-year-old sister with reduced
      visual acuity (0.16 and 0.2). CONCLUSION: There are few descriptions of the
      association of macular dystrophy and hypotrichosis. The combination of
      hypotrichosis and macular dystrophy could make genetical analysis easier.
      Mutational analysis of the TIMP-3 gene that has previously been associated with
      Sorsby fundus dystrophy did not reveal any disease-causing mutations in our
      patients.

PMID- 9623261
TI  - [Histamine in tears in allergic rhinoconjunctivitis].
AB  - The classic clinical symptoms of allergic conjunctivitis (type I allergy)-
      itching and lacrimation--are the effect of histamine. Determination of histamine
      levels in tears may be useful in evaluating the dynamics of local histamine
      release in connection with the clinical findings. PATIENTS AND METHODS: Between
      1.7.1994 and 31.6.1995 we analyzed the histamine levels in tears and investigated
      the clinical symptoms (score of 0-3) of 32 hyposensitized pollen-sensitive
      patients (14 males and 18 females, aged 18-45 years, group I) and of 32 controls
      (group II) without any allergic disease, performed in each case once in season
      and once out of season. Tear production and composition were measured by
      Schirmer's test and tear break-up time at the same time. The histamine levels of
      the tear samples (obtained by microcapillary method) were analyzed by
      electrochemical determination. RESULTS: In group I there was a highly significant
      increase of the mean histamine level from 0.89 +/- 2.22 ng/ml (out of season) to
      7.71 +/- 7.51 ng/ml (in season) for the right eye and from 0.73 +/- 2.36 ng/ml
      (out of season) to 9.51 +/- 9.07 ng/ml (in season) for the left eye (P = 0.0000).
      The histamine level in tears of the controls (group II) was below the detection
      limit in all samples. The seasonal histamine level were higher with the severity
      of atopy (Erlangen atopy score). There was no significant influence of age and
      gender. The reduction of allergic symptoms during hyposensitization was not
      comparable to the degree of seasonal histamine level. Compared with the clinical
      findings, the histamine level in tears did not correlate with the symptoms of
      lacrimation, itching and conjunctival hyperemia. CONCLUSION: The histamine level
      in tears alone is not useful as a marker for the clinical severity of this
      atopyassociated disorder and for the efficacy of the anti-allergic therapy. After
      standardization of the determination method and the identification of other
      soluble mediators simultaneously, the histamine level in tears can be used as one
      part of a profile of mediators to evaluate the clinical symptoms.

PMID- 9623262
TI  - [Automobile driving fitness of patients with nystagmus].
AB  - BACKGROUND: By law, applicants for driver's licenses not only have to have
      sufficient vision, but also have to use this sight reliably. The nystagmus
      patient takes advantage of ocularly induced head turns and other forms of
      compensation. In the approved test procedures he is deprived of such
      compensations. MATERIALS AND METHODS: The eye movements of a nystagmus patient
      were recorded oculographically. He was allowed to use compensatory mechanisms of
      body posture and movement for stabilization of vision. RESULTS: The nystagmus
      patient can achieve better visual performance when he is allowed to utilize
      complex segmental body movements for stabilization of vision. CONCLUSIONS: It is
      proposed that test procedures for visual performance in traffic be altered as
      follows: nystagmus and abnormal head postures are admittable if sufficient
      binocular vision is achieved. The test may use illustrations of traffic
      situations containing relevant details such as traffic signs. These are to be
      understood by the test person on triplicate presentation.

PMID- 9623263
TI  - [Prospective comparison of 2 multi-focal lens models].
AB  - BACKGROUND: The functional results of two different types of multifocal
      intraocular lenses (based on the diffractive and refractive principle,
      respectively) were investigated prospectively. MATERIALS AND METHODS: Altogether
      50 patients who had a multifocal lens implanted were examined 4-6 weeks
      postoperatively. Visual acuity for distance and near vision, contrast
      sensitivity, low contrast visual acuity and glare visual acuity were
      investigated. RESULTS: Distance visual acuity, contrast sensitivity, low contrast
      visual acuity and glare visual acuity did not show significantly different
      results. Near visual acuity was statistically significantly better with the
      diffractive type of multifocal lens (because of a stronger adjustment for near
      vision). When the focus depth was tested by defocus curves, both lenses had
      better results within different areas of defocus. CONCLUSIONS: All patients in
      both groups showed satisfactory results. When choosing a multifocal intraocular
      lens, the individual needs of each patient should be taken into consideration.

PMID- 9623264
TI  - [Transplantation of autologous submandibular glands in very severe
      keratoconjunctivitis sicca. 2 year outcome].
AB  - INTRODUCTION: The conservative treatment of the most severe cases of
      keratoconjunctivitis sicca (KCS) can be sometimes frustrating. Especially with an
      underlying autoimmunologic disorder, even the application of artificial tears as
      often as every 5 min may not prevent further damage to the ocular surface. A
      microvascular transplantation of the autologous submandibular gland (SG) can be
      performed by a maxillo-facial surgeon as an alternative approach for those cases.
      We report 2 years of ophthalmological experience with the results of this
      procedure. MATERIAL AND METHODS: To date 27 operations have been performed in 23
      patients. The SG was moved from its natural site into the temporal fossa. The
      secretory duct was implanted into the conjunctival fornix and the gland's vessels
      connected to the temporal artery and vein. A complete ophthalmological
      examination has been performed in 25 eyes of 21 patients up to 1 year and in 11
      eyes of 9 patients 2 years after surgery. RESULTS: Three months and 1 year
      postoperatively 19 of 25, and 2 years postoperatively 8 of 11 transplants
      remained vital. The baseline secretion increased in patients with a vital
      transplant from an average of 1.6 +/- 1.3 mm before the operation to 16.2 +/-
      11.3 mm after 3 months and 20.6 +/- 10.6 mm after 1 year. Ten of 19 vital grafts
      were reduced 1 year after transplantation in a minor second procedure to control
      an increasing epiphora. Subsequently baseline secretion was reduced to 13.6 +/-
      8.2 mm 2 years after transplantation. Patients with a vital graft reported in 84%
      of cases (16 of 19) at 3 months, and 79% at 1 year (15 of 19) and 2 years (7 of
      8), a strong relief of dry eye symptoms. In 58% (3 months), 79% (1 year) and 63%
      (2 years) of the eyes with a vital transplant all artificial tear substitution
      could be stopped. Break-up time increased significantly, resulting in reduced
      bengal rose staining. CONCLUSION: The transfer of the autologous SG into the
      temporal fossa can be used to provide patients with very severe KCS with a
      continuous, endogenous source of ocular lubrication. Despite surgical denervation
      the graft maintains a sufficient baseline secretion over a period of years.
      Subjective symptoms and the application of pharmaceutical lubricating substances
      are reduced to a large extent. If epiphora occurs, it can be controlled by
      surgically reducing the transplant. The influence of SG saliva on the ocular
      surface is the object of ongoing studies.

PMID- 9623265
TI  - [Eye manifestations in systemic vasculitis].

PMID- 9623266
TI  - [HLA-antigens and ulcerative colitis in Spain].

PMID- 9623267
TI  - HLA-DR2 gene and Spanish patients with ulcerative colitis.
AB  - BACKGROUND: An association with class II MHC genes has been described in
      ulcerative colitis, as in other diseases with immunological pathogenesis.
      Heterogeneous results have been reported, depending on the studied population.
      OBJECTIVE: To study the importance of these genes in our population, mainly the
      alleles of group HLA DR2 (gene HLA-DRB1). PATIENTS AND METHODS: We studied a
      total of 107 patients diagnosed of ulcerative colitis and 200 unaffected
      controls. Complete information about sex, age, family antecedent, age of onset,
      localization, complications, surgery and treatment was obtained from these
      patients. DNA was extracted from peripheral blood leukocytes and all the
      individuals were HLA-DRB1 genotyping. RESULTS AND CONCLUSIONS: We conclude that a
      positive association exists between DR15 and ulcerative colitis (p < 0.05). This
      positive association was characterized and various clinical parameters were
      analyzed, being concluded that DR1501 is more frequent in this disease (p < 0.05)
      and in benign manifestations; the frequency of the allele DR1502 was also found
      to be elevated in severe manifestations.

PMID- 9623268
TI  - Establishment of an experimental model of colon cancer which replicates the
      regional extension pattern of human colorectal adenocarcinoma.
AB  - OBJECTIVE: The aim of this study was to develop an experimental model of colon
      adenocarcinoma based on the orthotopic implantation of tumor cells in syngenic
      rats, which reproduces the regional extension pattern of human colorectal
      adenocarcinoma. EXPERIMENTAL DESIGN: Cell cultures: cell line DHD/K12-PROb.
      ANIMALS: BD-IX rats. Tumour implantation: intra-caecal injection containing 1 x
      10(6) cells in 0.25 ml of PBS. DESIGN: randomized observation study of three
      groups until five rats were shown to have cancer implantations in each group:
      GROUP I: sacrificed one week after the injection (n = 6), GROUP II: sacrificed
      two weeks after the injection (n = 9), GROUP III: sacrificed four weeks after the
      injection (n = 10). MEASUREMENTS: macroscopic and histological examination, with
      particular emphasis on caecal lesions. Tumours were classified according to the
      TNM system (UICC, 1987). RESULTS: GROUP I: tumors were found in 83% of cases
      (5/6), 4 of which were classified as T1N0M0 and 1 as T2N0M0. GROUP II: tumour in
      55.5% of cases (5/9). One was classified as T1N0M0, 3 as T2N0M0 and 1 as
      T3N0MPER. GROUP III: tumors were found in 50% of cases (5/10). Two were
      classified as T4N0M0, 2 as T4N1MPER, and 1 as T3N1MPER. The degree of wall
      infiltration of the tumor showed statistical differences between groups I and III
      and groups II and III (p < 0.05). CONCLUSIONS: Our model offers a step by step
      reproduction of events described for human colorectal adenocarcinoma. It was
      therefore easy to predict how long it would take to achieve a degree of local
      extension, which is essential in the design of cancer experiments. Moreover, this
      model has the advantage that it uses immunocompetent rats, which facilitates the
      methodology.

PMID- 9623269
TI  - ABO blood groups, rhesus factor and Helicobacter pylori.
AB  - BACKGROUND: The aim of this study was to demonstrate an association between
      Helicobacter pylori infection, ABO blood groups and Rhesus factor; providing the
      association between duodenal ulcer and O group blood as well as the former and H.
      pylori infection. METHODS: Three-hundred and one healthy subjects were
      prospectively studied. In all of them ABO blood groups and Rhesus factor were
      determined by standard techniques. Systemic IgG antibodies against H. pylori were
      assayed using a quantitative enzyme-linked immunosorbent assay technique (Helico
      G, Porton, Cambridge, UK). RESULTS: The overall seroprevalence was 52.2%. H.
      pylori infection distribution was similar among ABO blood groups and Rhesus
      factor. No statistically significant differences were observed in mean values of
      IgG antibodies among different blood groups. CONCLUSIONS: Distribution of H.
      pylori seroprevalence does not differ between different ABO or Rhesus factor
      blood groups. This excludes a possible link between this microorganism and the
      high ulcer prevalence in O blood group.

PMID- 9623270
TI  - Retroperitoneal liposarcomas. Study of 10 cases.
AB  - INTRODUCTION: Retroperitoneal liposarcomas are unusual tumors. Their biological
      and clinical features different from other retroperitoneal sarcomas. AIM: To
      analyze our series of retroperitoneal liposarcomas. PATIENTS AND METHODS:
      Retrospective study of 10 patients with retroperitoneal liposarcoma diagnosed in
      the last 16 years at our institution. Symptoms, diagnosis, treatment and
      prognosis were analyzed. RESULTS: Radical resection was done in all cases.
      Postoperative mortality was 10%. Complementary treatment was considered in each
      patient. Recurrent disease occurred in 8 patients (14 recurrences), during follow
      up. In 42% of them recurrences were resected. Actuarial 5-year survival rate was
      44%. CONCLUSION: Poor prognosis of retroperitoneal liposarcoma is due to its high
      recurrence rate.

PMID- 9623271
TI  - Preoperative chemotherapy followed by esophagectomy compared with surgery alone
      in the treatment of squamous cell carcinoma of the esophagus.
AB  - The aim of this study is to assess the effect of concomitant preoperative radio
      chemotherapy in the treatment of epidermoid esophageal cancer. We studied a total
      of 45 patients, divided into two groups. Group I consisted of 20 patients
      diagnosed with epidermoid esophageal cancer who had been treated initially with
      esophagectomy. Group II consisted of 25 patients treated with preoperative
      radiotherapy and two cycles of chemotherapy (cisplatin and 5-fluorouracil), one
      at the beginning and the other at the end of the radiation treatment, on whom an
      esophagectomy was subsequently performed. The clinical characteristics were
      similar in both groups. In group II, there were 12 cases (48%) with absence of
      tumor in the esophageal wall, three of which had node involvement. The operative
      mortality was similar in both groups (10% and 8% respectively). The only
      significant difference found in the postoperative complications was the incidence
      of anastomotic leak; but this was related to the different esophagectomy
      techniques used rather than the type of therapy. A decrease in the number of
      patients with tumor recurrence was observed in Group II, especially where the
      local component was concerned. The best actuarial survival rate at five years was
      in patients with no presence of tumor after neoadjuvant treatment (44.4%).
      However, the radio-chemotherapy seems not to have had any benefit in cases with
      node involvement.

PMID- 9623272
TI  - [New antiviral agents in the treatment of chronic hepatitis B and C].
AB  - Interferon (IFN) is the drug universally used in the treatment of B and C chronic
      hepatitis. Due to its low efficacy, 40% in the treatment of chronic hepatitis B
      and 10-20% in the treatment of chronic hepatitis C, and to its adverse events, in
      some cases severe, new antiviric molecules are being investigated. Lamivudin,
      famciclovir and the association of ribavirin and IFN are the more relevant and
      will be clinically accepted in an immediate future. It is also probable that
      rigid indications for hepatic transplantation in patients with liver cirrhosis by
      B virus change in the next years due to the use of these new antiviric drugs
      before and after transplantation. In this revision we analyze the current
      situation of these new therapies. However, most information come from pilot
      studies, and multicentric randomized studies are needed to establish firm
      conclusions about the role that these new therapies are going to play in the
      treatment of viral chronic hepatitis.

PMID- 9623273
TI  - [Endoscopic diagnosis of an ileocolic intussusception in an adult].
AB  - Although intussusception is the most frequent cause of intestinal obstruction in
      children, it only represents 5-10% of all adults. The preoperative diagnosis is
      difficult and it is rarely done by endoscopy. We present a case of adult
      ileocolic intussusception caused by an ileon terminal hamartoma. The diagnosis
      was done by colonoscopy.

PMID- 9623274
TI  - [Cecal ulcer associated with acetyl salicylic acid].

PMID- 9623275
TI  - [Adenosquamous carcinoma of the colon. A rare entity of uncertain prognosis].

PMID- 9623276
TI  - [Chylothorax and hepatic cirrhosis].

PMID- 9623277
TI  - [Gastric duplication cyst in an adult].

PMID- 9623278
TI  - [Cyclosporine A in treatment of enterovesical fistula of Crohn's disease].

PMID- 9623279
TI  - [What is the future of vaccines?].

PMID- 9623280
TI  - [Epidemiology of diseases preventable by vaccination].

PMID- 9623281
TI  - [Vaccinal coverage and its determinants in preschool children in Vaud canton in
      1996].

PMID- 9623282
TI  - [Routine vaccination schedule].

PMID- 9623283
TI  - [Routine vaccinations in adults or how to protect each stage of life?].

PMID- 9623284
TI  - [Which vaccines for the traveler?].

PMID- 9623285
TI  - [Vaccination against hepatitis B in Switzerland: towards a global strategy].

PMID- 9623286
TI  - [Influenza prevention].

PMID- 9623287
TI  - [Immunologic causes of vaccine failure].

PMID- 9623288
TI  - [Vaccination in patients presenting with a medical problem: precautions,
      contraindications].

PMID- 9623289
TI  - [Vaccine complications].

PMID- 9623290
TI  - [Vaccination promotion in the school system].

PMID- 9623291
TI  - [Combined vaccines and vaccine combinations].

PMID- 9623292
TI  - [Development of new pediatric vaccines: progress and challenges].

PMID- 9623293
TI  - [Switzerland and the genetic genie: June 7 voting polls].

PMID- 9623294
TI  - [A severe form of acute pancreatitis. Case report].

PMID- 9623295
TI  - [Primary repair of interrupted aortic arch in neonates].
AB  - In the Kardiocentrum, University Hospital Motol, Prague, protocol of the primary
      repair of interrupted aortic arch was introduced, and between 1993-1997, 15
      neonates aged 1-26 days (median 5 days) were operated on. Treatment with
      prostaglandins E for maintenance of the ductal patency, correction of metabolic
      acidosis, and treatment of all complications were necessary before surgery. The
      correction was performed from the midline sternotomy approach, in extracorporeal
      circulation and deep hypothermia with circulatory arrest. Direct anastomosis
      between the ascending and the descending aorta was possible in all the patients.
      At the same time, associated heart lesions were corrected (ventricular septal
      defect in 13, persistent truncus arteriosus in 3, subaortic stenosis in 2,
      transposition of the great arteries, double-outlet right ventricle and aortico
      pulmonary window in 1 patient, each). Four (26.7%) patients died after surgery.
      Out of the first 6 neonates 3 (50.0%) died, but out of the subsequent 9 patients
      only 1 (11.1%) died. Reoperation was necessary in 2 patients. All 11 early
      survivors are alive and doing well 8-54 months after the repair. In one of them
      restenosis at the site of aortic anastomosis and hemodynamically significant
      subaortic stenosis occurred. All the remaining patients have a nonrestrictive
      aortic anastomosis. Primary repair of interrupted aortic arch and associated
      heart lesions can be performed in a neonate with reasonable mortality. Treatment
      of complications is necessary before surgery. Results depend especially on the
      patient's clinical condition and experience of the center.

PMID- 9623296
TI  - [Surgery of recurrent inguinal hernia using the Lichtenstein technique].
AB  - The authors evaluated a group of patients operated in 1993-1996 on account of
      relapsing inguinal hernia by Lichtenstein's technique. During an average follow
      up period of 24 months 28% of the patients had another relapse of inguinal
      hernia. Because of the poor results the authors changed in January 1997 the
      surgical tactics in relapsing inguinal hernias. They operate by Nyhus
      preperitoneal approach and by laparoscopy transabdominally, placing a net in a
      preperitoneal position (TAPP) with subsequent follow-up of the patients.

PMID- 9623298
TI  - [Splenectomy--a complication of left-sided nephrectomy].
AB  - Iatrogenic injuries of spleen complicating left transperitoneal nephrectomy are
      the third reason of the injury of the spleen during abdominal surgery. This
      article deals with procedure of surgical freeing of file spleen from its fixing
      system with aim to avoid of its injury. Authors revalue all cases of left
      nephrectomy which was complicated with splenectomy, on their urology department
      during last ten years.

PMID- 9623297
TI  - [Coagulopathy as an unusual manifestation of splenic artery aneurysm. Case
      report].
AB  - Meticulous examination of patient treated for infertility with clinical signs of
      coagulopathy reveals lienal artery aneurysm. Such presentation of mentioned
      pathology is very rare. Surgical resection of aneurysm enabled to cure
      coagulopathy and very probably infertility as well.

PMID- 9623299
TI  - [Arterial thrombosis of the upper extremity treated with a combined approach].
AB  - The authors present the case-history of a 49-year-old female patient with
      arterial thrombosis of the upper extremity with compression of the first rib. The
      patient was successfully treated by combined continual and pulsed spray
      thrombolysis with subsequent resection of the first rib.

PMID- 9623301
TI  - [The concept of traumatology centers].

PMID- 9623300
TI  - [Explorative thoracotomy in patients with bronchogenic carcinoma].
AB  - The authors analyse in a retrospective study a group of 31 patients with
      explorative thoracotomy, which was performed on account of inoperable
      bronchogenic carcinoma. The causes of inoperability were assessed and the period
      of survival after explorative thoracotomy was evaluated. From the total number of
      496 patients indicated in 1985-1990 for surgery on account of bronchogenic
      carcinoma 465 pulmonary resections were made and 31 (6.25%) explorative
      thoracotomies. In all these patients the c TNM and p TNM classification was
      assessed. Disagreement in the evaluation of these parameters was found in
      particular in parameter T which was in agreement only in three instances.
      Conversely agreement was more frequent in parameter cN and pN (n = 18). The most
      frequent cause of inoperability was penetration of the tumour into the
      mediastinum (n = 25). Death within 30 days after surgery was not recorded in the
      group, three patients of 31 survived 5 years after exploration. Explorative
      thoracotomy did not exert a negative effect on the period of survival which
      corresponded to the given stage of the disease. Due to improving preoperative
      examination methods the number of explorative thoracotomies will probably decline
      in future, but at present it cannot be completely eliminated.

PMID- 9623302
TI  - [Rupture of the trachea and main bronchus after intubation].
AB  - The authors present two cases of post-intubation perforation of the trachea and
      main left bronchus resp. One was diagnosed incidentally during thoracotomy, on
      the second to third day after attempted intubation during which perforation
      occurred. The patient's life was threatened by the development of ARDS syndrome.
      The authors emphasize therefore the necessity of acute tracheobronchoscopy when
      perforation of the major airways during difficult intubation is suspected.
      Uncertain suture of the pars membranacea should be covered by the oesophagus.

PMID- 9623303
TI  - [Revascularization of the aortoiliac arteries using stents].
AB  - The authors summarised their three year experience with endovascular treatment of
      the aortoiliac artery obstructive lesions using stents and transluminal
      angioplasty. Fifty-seven patients (61 limbs) underwent stent implantation to
      treat claudications (n = 50 limbs), rest pain (n = 6), non-healing defects (n =
      4) and one patient was asymptomatic (n = 1). After stent placement patients were
      followed-up using clinical and duplex ultrasound examinations at 3 months and 6
      months thereafter. Immediate angiographic success was achieved in all cases.
      Three serious complications were observed. Percutaneous reinterventions because
      of stenosis inside the stent were performed in 7 patients (7 limbs). The primary
      patency rates were 92% at 1 year, 88% at 2 years and 86% at 3 years. Cumulative
      primary assisted patency were 98% (mean follow-up 15.8 months, range 3-47
      months). Regular clinical and ultrasound follow-up examinations can reveal the
      asymptomatic instent stenosis and percutaneous reinterventions can improve long
      term stent patency.

PMID- 9623304
TI  - [Spermatoceles and assisted reproduction].

PMID- 9623305
TI  - [Microsurgery and micromanipulation in the treatment of male infertility: results
      of a one-year investigation].
AB  - A one-year study of 51 infertile couples, 47 couples evaluated--25 cases of
      testicular azoospermia and 22 cases of obstructive azoospermia. The mean age of
      the men in the group is 33 years (22-48 years). The follow-up period is 1-18
      months. In 17 instances microsurgical epididymal sperm aspiration--MESA was made,
      five times testicular sperm aspiration--TESA and in 25 men testicular sperm
      extraction--TESE was used. In the group with testicular azoospermia it proved
      possible to obtain sperm in 12/25 cases, i.e. in 48%. In men with obstructive
      azoospermia all aspirations were successful, i.e. the yield was 100%. In this
      group five infants were born, another seven pregnancies are under way. Thus
      regardless of the etiology of male infertility 12/47 cases, i.e. 25.5%, were
      successfully resolved. When using differentiated evaluation of the two groups the
      results are as follows: in the group with testicular azoospermia one infant were
      born and five pregnancies are under way, i.e. 40.9%.

PMID- 9623306
TI  - [Fournier's gangrene].

PMID- 9623307
TI  - [Indications for enteral nutrition in surgery].
AB  - Survey of basic indications of enteral nutrition in Surgery. 1. Application in
      preoperative preparation. 2. Postoperative preparation in malnutritive and
      critically-ill patients, at early stage. 3. EN applied also for accelerated
      motility of the stomach and bowels after major operations (in retroperitoneal
      operations). 4. Application in traumatology: polytraumas, burns, subsequent
      sepsis, multiorgan failure; also in specific therapy, e.g. traumatic fistulae of
      GIT. 5. Use in acute and chronic pancreatitis. 6. Use of enteral probe in special
      states (e.g. in treatment of fistulae in upper and lower parts of GIT (dehiscence
      of anastomosis, bowels ruptures). 7. Application in the syndrome of short
      intestine. 8. Use in reconvalescence after severe operations (sipping) 9.
      Application in terminal cachectic states.

PMID- 9623308
TI  - [Initial experience with treatment of choledocholithiasis using shock waves].
AB  - From March 1996 till August 1997 at the First Surgical Clinic in Olomouc 18
      patients with concrements in the biliary pathways were treated by shock waves.
      All patients were older than 68 years; residual choledocholithiasis was involved
      which could not be eliminated during ERCP because of the size of the size of the
      stone. In 125 instances treatment was successfully terminated, i.e. by crushing
      the stones and their elimination. Only in three patients it was necessary to
      resolve the situation by surgery. The authors confirmed that it is possible to
      treat by this method patients with choledocholithiasis and avoid the risk of
      surgery in particular in older patients.

PMID- 9623309
TI  - [Axillo-axillary contralateral arteriovenous anastomosis with interposition of a
      Diastat-Gore prosthesis for dialysis].
AB  - The authors give an account of their experience with establishment of an
      arteriovenous fistula for dialysis using interposition with a DIASTAT-GORE
      prosthesis between the axillary artery and the contralateral axillary or inner
      jugular vein and its localization on the anterior thoracic wall. The method is
      apt in patients with a primarily unsuitable or secondarily surgically exhausted
      autologous circulation of the upper extremities.

PMID- 9623310
TI  - [Restoration of digestive passage after total gastrectomy].
AB  - In a group of 20 patients the authors evaluate possibilities of reconstruction of
      the digestive tract after TGE from the aspect of quality of life. The evaluating
      criterion are subjective complaints, the necessity to restrict the volume of
      meals and evaluation of the gastric substitution. The authors did not find a
      significant difference between reconstructions using a Roux loop and bilateral
      interposition of a jejunal loop between the oesophagus and duodenum, while the
      consider the creation of a reservoir very beneficial for the patient.

PMID- 9623311
TI  - [Importance of examination of the portal circulation using contrast media when
      there are indications for surgical anastomosis].
AB  - In a group of 79 patients hospitalized on account of haemorrhage associated with
      portal hypertension the authors evaluate the diagnostic yield of radiological and
      sonographic methods. Sonography is a non-invasive procedure and is useful for
      routine checks of the function of the anastomosis. Direct contrast examinations
      are essential in preoperative reflections and for evaluation of possible
      complications of an already established shunt. Indirect procedures are in the
      latter two instances inadequate and unreliable.

PMID- 9623312
TI  - [Hyperfunctional arteriovenous anastomosis and complications in hemodialysis
      access].
AB  - A less frequent late complication of arteriovenous fistulas for haemodialysis is
      the development of a hyperfunctional fistula with ischaemia of the peripheral
      part of the extremity. These complications affect autologous fistulas as well as
      those created by the graft. Ischemia is much more common when the brachial artery
      is used as the flow vessel. For prevention the size of the arterial anastomosis
      of the shunt is of basic importance. The authors evaluate therapeutic
      possibilities of this complication.

PMID- 9623313
TI  - [Palliative treatment of inoperable esophageal stenoses using stents: long-term
      results, complications].
AB  - The authors evaluate the effectiveness of palliative treatment of inoperable
      oesophageal stenoses by means of self-expandable stents in a group of 102
      patients and discuss complications. In all patients after implantation of the
      stent dysphagia improved by at least two degrees. Eighty nine patients of the
      group died, the mean period of survival was 107 days. At the time of evaluation
      13 patients survive, the mean survival period being 175 days. As to complications
      the authors recorded incomplete expansion of the stent (n = 1), fissuring of the
      tumour (n = 1), migration of the stent (n = 8), oesophagorespiratory decubital
      fistula (n = 4), ingrowth of the tumour into the stent (n = 4), obstruction of
      the stent by food (n = 7) and arterial haemorrhage (n = 1). The effectiveness of
      palliative treatment of inoperable oesophageal stenoses by self-expanding stents
      is high and prompt. The total number of complications is 22%, the mortality after
      surgery is zero. The majority of complications is easily resolved by methods of
      interventional radiology.

PMID- 9623314
TI  - [Brachial plexus paralysis due to leiomyosarcoma of the subclavian artery
      successfully treated by surgery].
AB  - The authors describe a rare case of surgical treatment of a paresis of the
      brachial plexus in a 63-year-old woman. The paresis improved significantly after
      extirpation of a tumour of the upper mediastinum which originated in the left
      subclavian artery and was classified as a leiomyosarcoma.

PMID- 9623315
TI  - [Isolated defect injuries of the common femoral and external pelvic veins].
AB  - The author describes the case-history of an injury of the common femoral and
      external pelvic vein. He describes the method of replacement of the loss using an
      autovenous graft formed from the trunk of the vena saphena magna which was split
      longitudinally and then sutured in a spiral fashion. The applied reconstruction
      method can be evaluated as reliable, technically feasible. The reconstruction is
      patent after two years and the affected extremity bears no signs of venostasis.

PMID- 9623316
TI  - [Cisapride (Prepulsid) in the prevention of postoperative gastrointestinal
      atony].
AB  - Administration of cisapride, 3 x 5 mg in a suspension one day before surgery and
      30 mg 3 and 8 hours after abdominal surgery with subsequent administration of 2 x
      30 mg in suppositories up to the time when oral ingestion is possible, hastens
      significantly the restoration of GIT motility as compared with placebo. It can be
      therefore recommended as effective medication in the prevention of complications
      caused by impaired motility of the digestive tract.

PMID- 9623317
TI  - [A knit vascular prosthesis of RaK collagen--a clinical evaluation study].
AB  - Vascular collagen prosthesis of RaK type (collagen-impregnated knitted
      prosthesis) made by Vyzkumny ustav pletarsky (Research Institute of Hosiery) in
      Brno was introduced into clinical practice in 1990. In comparison with previous
      type, the collagen-impregnated prosthesis has had a number of advantages and thus
      it gets into the interests of vascular surgeons. The report presented has given
      the results of clinical evaluating study carried out at the IInd Clinic of
      Surgery, Faculty of Medicine, Masaryk University, Brno according to the methods
      of EN 540 European Norm Proposal for clinical studies. The results obtained from
      evaluating a set of 107 patients created for this study (besides others, long
      term patency of 90.7%, or 0.9% incidence of infection of the vascular prosthesis
      of Szilagyi III type) have shown that nowadays we have at disposal a very good,
      reliable and economically acceptable vascular prosthesis of our provenience.

PMID- 9623318
TI  - [Development of peripheral nerve surgery].
AB  - In the submitted review the author deals with the development of peripheral nerve
      surgery (PN) from ancient times to the present time incl. hithero unpublished
      details. He analyses in great detail the period of the last 40 years which is
      divided into three stages--the mechanical, biological period and the period of
      neurotrophism. From the Second World War to the sixties the period bears the term
      mechanical. The results of reinnervation during this period were not satisfactory
      as the nerves were connected without the use of a microscope, in major defects
      they were connected under considerable traction and the only criterion was the
      resistance against dehiscence. Significant improvement of results of regeneration
      of PN was recorded during the biological period. Mechanical ideas were overcome
      and biological and physiological reactions of the peripheral nerves were taken
      into account. Suture of nerves under traction was refuted and into clinical
      practice the surgical microscope, microsurgical technique and microsurgical
      autotransplantation with a nervous graft were introduced. The anatomical
      structure of the nerve with a plexiform pattern of the fascicles became however
      the limitation of surgical methods. After discovery of NGF (nerve growth factor)
      we can speak of the onset of a new period, neurotrophism. In laboratory
      experiments many substances are studied and theoretically new non-surgical
      possibilities how to promote regeneration lie ahead. However they cannot be
      applied yet in clinical practice. In injuries of peripheral nerves the only
      correct reconstruction method is still microsuture of the nerve and in case of
      losses microsurgical autotransplantation using a nerve graft.

PMID- 9623319
TI  - [Direct myocardial revascularization by antero-lateral minithoracotomy].
AB  - The authors present the case of successfully treated patient with CAD, operated
      from left anterolateral minithoracotomy. Angiographic control two years later
      presents fully patent anastomosis without any signs of stenosis.

PMID- 9623320
TI  - [Gangliocytic paraganglioma of the duodenum].
AB  - Gangliocytic Paraganglioma of the duodenum is rare neuroendocrine tumor. This
      type of the tumor can cause bleeding into the gastrointestinal tract and
      epigastric pain in this region. It can be difficult to differentiate this tumor
      from the primary tumor of the head of the pancreas growing secondary to the
      duodenum. The authors describe one such misdiagnosed case treated finally
      successfully by hemipancreatodecodenectomy.

PMID- 9623321
TI  - [Injury of the hepatic artery].
AB  - Injury to the proper hepatic artery is rare but life threatening condition. The
      author presents rupture of the proper hepatic artery treated successfully by
      primary repair. Although ligation of injured proper hepatic artery is considered
      safe, primary repair is available when possible considering the condition of the
      patient. Both primary repair and ligation have high mortality rate.

PMID- 9623322
TI  - [Interventional procedures in patients after vascular reconstructive surgery of
      the lower extremities].
AB  - This study reports the results and complications of local thrombolysis therapy of
      recently occluded grafts manifested by acute ischemia in comparison with
      transluminal angioplasty of graft stenoses. Stenoses were diagnosed by means of
      ultrasound (asymptomatic patients) or manifested by claudications. The aim of our
      study is to emphasize the difference between efficacy of these two kinds of
      treatment and their difficulties. Fourty three patients were treated in the
      period of 39 months (March 1994-June 1997). Sixty seven interventional procedures
      were done, including 32 local thrombolysis in 20 patients and 35 angioplasties in
      23 patients. Types of grafts were: aortofemoral (n = 8), ilicofemoral (n = 4) and
      one aortotibioposterior, femoropopliteal vein (n = 18) and synthetic (n = 9) and
      two distal tibioposterior bypasses. Fourty one bypasses were created due to
      arteriosclerotic occlusion, one for traumatic amputation and one due to stenosis
      after perinatal catheterization. The period between surgery and intervention
      varied from 1 month to 11 years (mean 33 months), the mean follow up period was
      13 months. Technical success rate in patients treated by local thrombolysis was
      69% (n = 22). Midterm graft patency in the this group is 40% (n = 8) with 95% (n
      = 19) limb salvage. In patients treated by transluminal angioplasty was technical
      success rate 97% (n = 34). In this group is patent 96% (n = 20) bypasses with 31%
      (n = 4) restenoses. All patients with patent grafts have a good run-off with at
      least 2 patent calf arteries. Six complications occurred during local
      thrombolytic therapy. Our results indicate that despite of the high initial
      success rate are the late results poor in the group treated by thrombolysis
      because of the high rate of rethromboses. The result depends on number of patent
      calf arteries. Results in patients treated by angioplasty only are much better
      with lower risk of complications during procedure. Our results prove that it is
      better to follow patients after lower limb bypass surgery by ultrasonography and
      perform angioplasty when stenoses occur.

PMID- 9623323
TI  - [Therapy of anthracycline-resistant metastatic breast carcinoma].
AB  - Treatment of anthracycline-resistant metastatic breast cancer with new
      antineoplastic agents remains a challenge for the next future. The 5-year
      survival for this disease is only 15%, and hormonal and chemotherapeutic options
      remain essentially palliative. New treatment drugs or drug combinations are
      urgently needed to improve the prospects for patients with metastatic breast
      cancer, particularly for those with disease characteristics indicating a
      particularly poor prognosis. Taxanes are promising new drugs and have shown
      encouraging activity in patients with disease resistant to anthracyclines and in
      patients with visceral metastases, both with a poor prognosis. Paclitaxel (taxol)
      is applied with a dose of 175 mg/m2 in a 3 hour infusion and docetaxel (taxotere)
      with a dose of 100 mg/m2 q 3 weeks. Remission rates are expected between 6-30%
      for taxol and between 29-48% for docetaxel. Highly active in patients with
      anthracycline-resistant disease appears to be the vinca-alkaloid vinorelbine too.
      In patients treated with adriamycin objective remissions between 15-33% can be
      obtained. The long time known 5-fluorouracil comes to the third place of the
      effective drugs. Continuous infusion or addition of folic acid increases the
      intracellular efficacy and results in 5-53% objective remissions. In second-line
      chemotherapy platin-analogues together with etoposide, vincristine and 5-FU
      achieve partial or complete remissions between 19-37% for cisplatin containing
      and 5-12 for carboplatin containing combinations. This may eventually play a role
      especially if three drug combinations containing paclitaxel, epirubicin and
      vinorelbine will be used, which are reported to result in 20-33% complete
      response rates and 66% objective response. The indication for other new drugs
      like tomudex, topoisomerase-I-inhibitor and gemcitabine for anthracycline
      resistant breast cancer remains to be established in multicenter studies.

PMID- 9623324
TI  - [Studies with high-dose chemotherapy and subsequent autologous stem cell
      transplantation in breast carcinoma].
AB  - Survival rates for several subgroups of patients with breast cancer treated with
      conventional therapy remain poor. Only about 30% of patients with primary breast
      cancer involving more than 9 axillary lymph nodes remain disease-free at 5 years
      from diagnosis despite surgery, conventional-dose chemotherapy and radiotherapy.
      Metastatic breast cancer with 5 year survival rates of about 3% generally
      represents incurable disease. Chemotherapeutic agents are conventionally limited
      by side effects. The easy procurement of haematopoietic stem cell support through
      mobilization of peripheral blood progenitors has spurred the development of new
      strategies employing high-dose treatment for treatment of high risk breast
      cancer. Autologous stem cell support antagonizes chemotherapy-induced
      myelotoxicity and thereby allows dose escalation by a factor of 1.5 to about 20.
      Pilot studies evaluating significant dose escalation in adjuvant treatment of
      patients with advanced disease have resulted in an apparent improvement in event
      free survival rates to over 70%. Repetitive applications of chemotherapy at
      myeloablative doses are now increasingly being used. Data from prospectively
      randomized phase III trials will not be available before the end of 1998. For
      metastatic breast cancer one prospective, randomized clinical trial has been
      published. Results are significantly better for patients who have been treated by
      high-dose chemotherapy compared to patients who received conventional
      polychemotherapy (median survival 90 vs. 45 weeks). For methodological reasons
      (small patient numbers, patient selection, weak standard therapy etc.) results
      from the trials cited above are under discussion. Until publication of further
      results from ongoing phase III trials HDC for breast cancer remains experimental
      and should not be given outside of clinical trials.

PMID- 9623326
TI  - [Considerations in rational use of tumor markers in breast carcinoma].
AB  - The objective of this review is to determine clinical practical guidelines for
      the use of serum tumor markers in the care of breast cancer patients outside of
      clinical trials. Mucin antigens (CA 15-3, MCA, CA 549) and CEA are established
      markers in breast cancer. Owing to their low sensitivity, none of these markers
      can be recommended for screening, diagnosis or staging. During follow-up,
      increasing marker levels may indicate recurrence 3-6 months earlier than clinical
      and radiological examinations in about 40-50% of patients. However, the clinical
      benefit of this lead-time is not established. Tumor markers are able to monitor
      response to treatment in 70-80% of patients with metastatic breast cancer.
      However, paradoxical changes of the markers especially in the beginning of
      treatment, the insufficient concordance with tumor activity in 20-30% of the
      women, and the lack of curative therapy regimens limit the prospective clinical
      use of the markers in the individual patient. Therefore, marker changes require
      confirmation by radiological methods in most cases. The present data are
      insufficient to recommend routine use of tumor markers alone for monitoring
      breast cancer patients after primary treatment or during palliative therapy.
      However, in the absence of readily measurable disease (e. g. bone metastases)
      continuously increasing marker levels may be used to indicate treatment failure.
      If high-dose chemotherapy in metastatic breast cancer renders to be effective,
      the clinical impact of tumor markers will increase considerably. Until that time,
      the analytical performance and the sensitivity of the established marker assays
      should be improved, and the clinical role of newer marker tests (TPS, CA 27.29)
      should be evaluated.

PMID- 9623325
TI  - [Aromatase inhibitors--new possibilities in treatment of breast carcinoma].
AB  - Aromatase inhibition is now an acknowledged second line treatment modality for
      advanced breast cancer in postmenopausal women. Aminoglutethimide is an inhibitor
      of adrenal steroid biosynthesis and blocks the conversion of cholesterol to
      pregnenolone, and therefore reduces levels of adrenal androgens, which are a
      source of estrogens in both premenopausal and postmenopausal women.
      Aminoglutethimide has produced antitumor response rates of 35% in unselected
      patients, most of whom have undergone prior therapy with either chemotherapy or
      hormonal manipulation. As is true of other hormonal responses, high response
      rates of up to 70% are observed in patients who are ER and/or PR positive. The
      reason why these drugs are currently used after tamoxifen is mainly due to the
      side effects of aminoglutethimide, which impairs the mineralocorticoid and
      glucocorticoid synthesis. New, less toxic compounds appear, which block the
      conversion of androstenedione to estrone and efficiently suppress plasma estrogen
      levels., e.g. formestane, anastrozole and letrozole. Aromatase inhibitors are now
      being compared to tamoxifen as first-line endocrine treatment in relapsing
      patients. If these trials confirm a similar or better response rate to new
      aromatase inhibitors compared to tamoxifen, the time will come to study them as
      the first line adjuvant treatment in non-metastatic disease.

PMID- 9623327
TI  - [Target volume and indications of radiotherapy in breast carcinoma].
AB  - Breast-conserving surgery is now commonly used to treat breast cancer. While
      mastectomy has been the traditional treatment for ductal carcinoma in situ, it is
      felt to be excessive in most cases. A great effort has been made to identify
      pathobiological characteristics of DCIS that can be used to identify patients
      best suited for wide local excision vs. wide local excision and breast
      irradiation. Mastectomy and conservative surgery plus irradiation offer a similar
      outcome in patients with early stage invasive breast cancer. Radiotherapy has not
      been shown to improve survival but is able to reduce significantly the rate of
      local recurrence, which is regarded as a very undesirable outcome. There is still
      controversy concerning the necessity of irradiation of the breast in all
      patients. Analysis of predictors of outcome cannot identify a subgroup of
      patients with a very low risk for local breast recurrence who might not require
      radiation therapy. In premenopausal, node-positive breast cancer patients XRT has
      a beneficial effect not only on locoregional but also on systemic recurrences.
      Radiotherapy has to be integrated for a pre- or postoperative consolidation in
      new treatment concepts for locally advanced breast cancer which use primary
      chemotherapy and immediate or subsequent breast radiation. Radiation of internal
      mammary chain and supraclavicular fossa after conservative surgery does not lead
      to an increase in clinically important skin or pulmonary complications. Its role
      is being evaluated in current multicentre studies.

PMID- 9623328
TI  - [Obstructive sleep apnea, CPAP treatment and adverse health effects].

PMID- 9623329
TI  - [Obstructive sleep apnea, CPAP treatment and adverse health effects.
      Counterpoint].

PMID- 9623330
TI  - [What is the role of minimal invasive endoscopic surgery in treatment of lumbar
      disk hernias?].

PMID- 9623331
TI  - [Sexual dysfunctions with antidepressive drugs--results of a physician survey].
AB  - In a survey throughout Switzerland 7.455 general practitioners and psychiatrists
      were mailed a questionnaire addressing topics in sexual medicine with regard to
      antidepressant medication, 940 completed questionnaires (response rate 12.5%)
      were evaluated. 77.6% of the responders agree that knowledge in sexual medicine
      is important or very important. Only one half of the physicians judge their
      competence in sexual medicine as fair or good. There are differences in sexual
      history taking between general practitioners and psychiatrists; the latter
      addressing more frequently sexual medicine related questions. Sexual dysfunction
      before and during therapy with antidepressants is observed less frequently than
      reported in other studies. Only half of the physicians counsel their patients
      when sexual dysfunction occur during therapy. Treatment strategies of
      antidepressant induced sexual side effects are rarely seen. The results emphasize
      the importance of knowledge and competence in sexual medicine for general
      practitioners and psychiatrists, both showing interest in continuing education on
      this topic.

PMID- 9623332
TI  - [Effect of a baby whey bath on skin physiology parameters in young children].
AB  - Although the skin of babies is very sensitive to irritants and baby baths are
      widely used in child care, there have been no investigations concerning their
      efficacy and safety so far. In the presented work we investigate the effect of a
      baby bath containing 80% and after another 2 weeks of treatment with a whey baby
      bath. During the study all infants were bathed at a temperature between 35 and 38
      degrees C for 5 to 15 min every other day. The results showed a slightly lower
      skin moisture, a lower skin-pH and after an initial minimal increase a reduction
      of skin redness values. However, none of the results were statistically
      significant. The tested baby bath was well tolerated by the babies' skin based on
      a reduction of skin-pH. In contrast to relatively aggressive soaps we found a
      protective effect of the tested baby bath on the acid mantle of the skin.

PMID- 9623333
TI  - [Severe chronic iron deficiency in a 17-year-old student].
AB  - A 17 year old male suffered from iron deficiency of undetermined cause for 2
      years. Iron substitution was able to correct it for short periods. With the
      exception of fatigue and recurring abdominal pain attributed to oral iron therapy
      no further symptoms were present. The physical status on admission was
      unremarkable. The laboratory detected intestinal disorders, an anemia of the
      chronic type without evidence for malignancy or renal failure suggested an
      inflammatory gastro-intestinal disorder. In spite of a twice negative noninvasive
      test for gluten-intolerance the clinician favored in his differential diagnosis
      non tropical sprue over inflammatory bowel disease (IBD, Crohn's disease,
      Whipple's disease). Histopathology of small bowel specimens did not indicate
      sprue. An ileo-colonoscopy revealed severe ulcerating ileitis and mild chronic
      colitis. The histologic specimen revealed a severe ileal inflammation with
      cosinophilia and the colon specimens epitheloid microgranuloma. These findings
      are highly compatible with the diagnosis of Crohn's disease. Iron deficiency
      anemia is common in Crohn's disease. In the current case it is due to disturbed
      iron uptake. Iron deficiency anemia as sole symptom of Crohn's disease is
      extremely rare.

PMID- 9623334
TI  - [Dysphagia as a symptom of myxedema].
AB  - We present a 79 year old female patient with dysphagia since two years. She
      showed also a lack of initiation and dysphonia. In the region of the larynx an
      edema was found and the tongue was hypertrophied. The X-ray examination
      demonstrated a dilated esophagus without impairment of the passage way.
      Esophagoscopy showed also important edema in the hypopharynx and the entry into
      the esophagus. The TSH-0 was 74.45 mmu/l, the T3 0.23 and the T4 was 24 nmol/l.
      Scintigraphically an only cherry-stone small region with active thyroid tissue
      was revealed. Severe hypothyroidism responsible for secondary dysphagia was
      diagnosed. L-Thyroxin was administered (150 micrograms/d). There was a dramatical
      improvement. The signs of edema and the dysphagia decreased. The examination a
      half year later demonstrated a patient without any dysphagia or edema. The
      symptom dysphagia is defined and an interdisciplinary approach emphasized.

PMID- 9623335
TI  - [Immobilizing muscle weakness accentuated in leg and proximal muscles].
AB  - A 54 year old waiter was referred to the hospital because of proximal muscle
      weakness, most pronounced in his legs, which progressed to an inability to stand
      or walk within weeks. Myopathy was diagnosed based on the muscle biopsy findings
      and myositis was ruled out by laboratory and biopsy results. Further
      investigations led us to exclude an endocrine cause, hypovitaminosis D,
      infectious myopathy or a paraneoplastic syndrome. Heteroanamnesis revealed severe
      alcoholism, lasting for more than 30 years. The presumed alcohol induced
      hepatopathy was confirmed by liver biopsy. There were no signs of an acute
      alcoholic myopathy, as the weakness had developed rather insidiously, there was
      no elevation of the CK serum level nor myoglobinuria and a type 2 fibre atrophy
      was found by muscle biopsy. As expected the weakness improved under abstention.
      Thus the final diagnosis of a chronic alcohol induced myopathy was established.

PMID- 9623336
TI  - [Fatigue and pollakisuria].

PMID- 9623337
TI  - 1988 National Maternal and Infant Health Survey: methods and response
      characteristics.
AB  - OBJECTIVES: The 1988 National Maternal and Infant Health Survey (NMIHS) was
      conducted by the National Center for Health Statistics to study factors related
      to poor pregnancy outcome, such as adequacy of prenatal care; inadequate and
      excessive weight gain during pregnancy; maternal smoking, drinking, and drug use;
      and pregnancy and delivery complications. METHODS: The NMIHS is a nationally
      representative sample of 11,000 women who had live births, 4,000 who had late
      fetal deaths, and 6,000 who had infant deaths in 1988. Questionnaires were mailed
      to mothers based on information from certificates of live birth, reports of fetal
      death, and certificates of infant death. Information supplied by the mother,
      prenatal care providers, and hospitals of delivery was linked with the vital
      records to expand knowledge of maternal and infant health in the United States.
      RESULTS: The response rates in all three components of the NMIHS differed
      according to the mothers' characteristics. Mothers were more likely to respond if
      they were 20-39 years of age, were white, were married, had fewer than four
      children, entered prenatal care early, had more prenatal visits, had more years
      of education, or resided in the Midwest Region. The percent of respondents was
      lower for teenage mothers, mothers of races other than white, and mothers with
      four or more children, little prenatal care, or fewer years of education. Mothers
      whose infants weighed less than 2,500 grams were less likely to respond in the
      live-birth and infant-death components than mothers whose infants weighed 2,500
      grams or more. CONCLUSIONS: The NMIHS will provide an invaluable tool for
      researchers and practitioners seeking solutions to perinatal and obstetric
      problems.

PMID- 9623338
TI  - Factors influencing the outcome of nerve repair.
AB  - The dependence of the nerve repair outcome on the following 7 factors was
      analyzed: regenerative potential of the interrupted nerve, local vascular and
      scar state, level of nerve lesion, applied surgical technique, length of nerve
      defect, preoperative interval and patient's age. Prospective study included 490
      ruptures of peripheral nerves, operated in two years period and the final outcome
      was established 24-30 months after reparation. The influence of the each of
      mentioned factors on the treatment outcome was tested in experimental groups, in
      which total homogenization existed, according to all other factors which could
      cause the differences in the repair outcome. The obtained results point out that
      local vascular and scar state, applied surgical technique and the age of patients
      between 16 and 50 did not influence significantly the final results of treatment.
      According to the intensity of regenerative potentials, three groups of nerves
      could be recognized: with excellent (radial, musculocutaneus and femoral nerves),
      with moderate (median, ulnar and tibial nerves) and with poor regenerative
      potential (peroneal nerve). The level of repair significantly affected the final
      outcome only for nerves with moderate regenerative potential (median, ulnar and
      tibial nerves), while for nerves with excellent (radial nerve) and poor recovery
      potential (peroneal nerve), differences in outcome after high, intermediate and
      low level repairs were not significant. The length of the defect did not
      influence significantly the repair outcome for nerves with excellent regenerative
      potential (radial nerve), while for other nerves significant linear correlation
      existed between length of the defect and the repair results. Linear correlation
      also existed between the repair outcome and the preoperative interval. Border
      values of the length of the defect and for preoperative interval were calculated,
      which gave minimal and maximal possibilities for the successful recovery after
      the repair.

PMID- 9623339
TI  - [Association of manifestations of chronic post-traumatic stress disorders and
      disseminated demyelinating disease of the central nervous system].
AB  - The study included 7 patients who were with clinically, laboratory,
      neurophysiologically and neuroradiologically confirmed associated occurrence of
      posttraumatic stress disorder of chronic course and disseminated demyelinating
      disease of the central nervous system. All the examinees were extendedly exposed
      to war stress, so it could be directly designated as the cause of posttraumatic
      stress syndrome and indirectly denoted as the trigger of immune disorder that
      brought to disseminated demyelination of the central nervous system.

PMID- 9623340
TI  - [Significance of inflammatory cytokines in the pathogenesis of IgA nephropathy].
AB  - Prospective study was performed on the concentrations of inflammatory cytokines
      IL-1, TNF and IL-6 in serum and urine (ELISA tests) were determined in the scope
      of total clinical-laboratory and histologic treatment in 59 patients with primary
      IgA nephropathy. Control group consisted of 20 healthy subjects. IL-6 was not
      detected either in serum of patients with IgAN, or in control examinees. TNF
      alpha and IL-1 beta were detected in control patients' sera and in patients with
      IgAN, but detected concentrations were not significantly different. IL-1 beta in
      urine was detected in 82.8%, TNF alpha in 90.0%, and IL-6 in 40% of our patients
      with IgAN. The concentrations of IL-1 beta were significantly higher compared to
      IL-1 beta concentrations in urine of healthy subjects and significantly
      correlated with the severity of glomerular and tubulointerstitial changes, as
      well as with the degree of proteinuria. Direct and indirect toxicity of TNF alpha
      on renal structures was confirmed in significantly higher concentrations of that
      cytokine in urine of patients with mesangial sclerosis of different percentage
      compared to the patients with isolated mesangial hypercellularity. Also in the
      patients with index of chronic lesion over 7 significantly higher TNF alpha
      concentrations in urine were found compared to the patients with lesion index 0-3
      and 4-7. Creatinine clearance was in negative correlation with TNF alpha
      concentrations in urine of our patients with IgAN. Concentrations of IL-6 in
      urine were in correlation neither with laboratory parameters of renal function,
      nor with the degree of histologic changes.

PMID- 9623341
TI  - [The effect of toxoplasmosis on occurrence of spontaneous abortions and anomalies
      in neonates in the Timok region].
AB  - ELISA was used for follow-up of protozoa Toxoplasma gondii infection in 2,778
      pregnant women in the Timok region during the five-year period (1989-1993). The
      study included 16.66% of all pregnant women in the region. Acute infection was
      registered in 17 (0.61%) and chronic infection in 1.266 (45.57%). Spontaneous
      abortions were registered in only 12 (0.43%) tested pregnant women. In relation
      to the total number of spontaneous abortions (865) in all pregnant women in the
      region spontaneous abortions in the studied group occurred in only 1.38% of
      cases. Anomalies in newborns were registered in a total of 3 (0.11%) cases. In
      relation to the total number of anomalies in newborns (194) from all deliveries
      in the region, the number of anomalies in newborn in the studied group was only
      1.54%. Toxoplasma gondii infection did not significantly affect the frequency of
      spontaneous abortions and anomalies in newborns of the Timok region during five
      year period.

PMID- 9623342
TI  - [Use of the maximal physiologic load test in the evaluation of functional values
      of newly made complete dentures and dentures rebased by the Rehm method].
AB  - There is a constant dilemma of dental practitioners in contact with patients in
      whom complete dentures have lost congruent relation toward supporting mucoosseous
      tegmen if new dentures should be made or rebased by change of denture base. The
      investigators who have studied those problems have been mostly concerned with
      problem of material and rebasing procedures of complete dentures. The aim of the
      study was to determine the functional value of unrebased, rebased by Rehm and new
      complete dentures and compare the time of initial functional adaptation of
      patients to rebased and new complete dentures. The study included 72 examinees.
      The functional value of complete dentures was estimated by test of masticatory
      muscles, bioelectrical activity by test of masticatory efficacy and by test of
      maximal physiological load. On the basis of the study it was concluded that
      complete dentures rebased by Rehm were in function worthier than unrebased, and
      the period of initial functional adaptation was missing. In the examinees with
      pair of newly made complete dentures, functional tests revealed the reduction of
      initial values after the new dentures were delivered. During the examination
      interval, progressive dynamics with tendency of establishing the optimal
      functional value and initial functional adaptation was revealed after 21 days.

PMID- 9623343
TI  - [Diagnostic, morphologic and therapeutic aspects of medulloblastoma].

PMID- 9623344
TI  - [Treatment of nephrotic syndrome in proliferative glomerulonephritis].

PMID- 9623345
TI  - [The heart as an endocrine organ].

PMID- 9623346
TI  - [Diagnostic and differential diagnostic problems in anxiety and panic disorders].

PMID- 9623347
TI  - [Modern understanding of pathophysiologic mechanisms in endogenous uveitis].

PMID- 9623348
TI  - [Significance of genetic-epidemiologic studies in research on disease etiology].

PMID- 9623349
TI  - [Left-sided gallbladder and hypoplasia of the right hepatic lobe--a rare
      congenital anomaly].
AB  - Ectopic gallbladder, followed by other abnormalities in the anatomy of liver,
      biliary-pancreatic system, and portal vein is very rare congenital defect. The
      patient with left-sided gallbladder, complicated chronic calculous cholecystitis
      and hypoplasia of the right lobe of liver was presented. The diagnosis of this
      abnormality was confirmed intraoperatively. After cholecystectomy, postoperative
      course in the patient was uneventful.

PMID- 9623350
TI  - [The Fahr syndrome].
AB  - Fahr's syndrome is a rare clinical entity consisting of certain metabolic,
      biochemical, neuroradiologic and neuropsychologic phenomena in which
      extrapyramidal phenomenology clinically dominates. In this report, primarily from
      educational reasons, we have presented a female patient, who was before
      admittance to our clinic examined in one Belgrade hospital for headache,
      stiffness of trunk and extremities and the diagnosis was migraine with depressive
      reactions. However, as the discomforts were persistent, she was admitted to our
      clinic and after the investigation, especially for the presence of extrapyramidal
      clinical phenomenology with dominantly pronounced increase of tonus with the
      presence of amorphous calcifications in basal ganglia on both sides it was
      concluded that she was suffering from Fahr's syndrome.

PMID- 9623351
TI  - [Chronic persistent hepatitis with an atypical clinical course].
AB  - Chronic persistent hepatitis is a form of chronic hepatitis with mild clinical
      course that does not require specific therapy. Diagnosis is established by liver
      biopsy. A 65 years old female patient, was admitted to the Clinic of
      gastroenterology with clinical and laboratory picture of obstructive jaundice
      with progressive deterioration. Obstruction was not found through performed
      examinations (US, CT, gastroduodenoscopy, ERCP). Viral liver infections as well
      as primary biliary cirrhosis were also excluded. Ultrasonically guided liver
      biopsy verified chronic persistent hepatitis. Specificity of this case was in
      atypical clinical course and treatment: obstructive jaundice clinical feature,
      rapid deterioration and corticosteroid treatment that led to the complete
      clinical and biochemical recovery.

PMID- 9623352
TI  - [The antiphospholipid syndrome--yesterday, today, tomorrow].
AB  - Antiphospholipid syndrome (APLS), is defined as the presence of antiphospholipid
      antibodies (APLA) associated with clinical phenomena of arterial or venous
      thrombosis, recurrent spontaneous abortions and thrombocytopenia. APLA represent
      the family of antibodies of different specificity. They are mostly directed to
      various anionic phospholipids (cardiolipin, phosphatidylcholine,
      phosphatidylserine, phosphatidyl acid and phosphatidyl ethanolamine). The part of
      APLA is directed towards epitope at the structurally changed beta-2-GPI, the so
      called anti beta-2-GPI antibodies and the hypothesis was established that the
      subgroup of APLA was directed towards complex of beta-2-GPI with the
      phospholipids and oxidized lipoproteins of high and very low density. This could
      explain the clinically observed association of mutual onset of thrombosis and
      atherosclerosis. The most frequent target tissues for APLA are endothelial cells,
      thrombocytes, monocytes, natural anticoagulant system and placenta. APLA can be
      detected in a serum with one of the following assays: testing of lupus
      anticoagulant presence, determination of anticardiolipin antibodies (ACLA)
      concentration by ELISA and by testing the false positivity of VDRL test (standard
      test for syphilis). The pathological base for so-called vasculopathy in APLS are
      arterial and venous thrombosis. Clinical manifestations of APLS are mainly the
      result of blood vessels' occlusion but the thrombotic mass deposition on the
      surface of the heart valves may also occur. Clinically APLS can be divided into
      primary and secondary one, and manifestations of the secondary APLS are mainly
      expressed in the patients with SLE. Some clinical and serological variants of
      primary APLS were also described. The tendency for thrombotic process as a
      crucial characteristic of the syndrome and the lack of inflammation, imposes the
      choice of antithrombotic and anticoagulant therapy.

PMID- 9623353
TI  - [Detection of antiphospholipid antibodies].

PMID- 9623354
TI  - Increased titer of anticardiolipin antibodies represents the risk for the
      development of ischemic brain disease in persons below 50.
AB  - The aim of this paper was to investigate the frequency of increased ACLA titer in
      patients with ischemic brain disease (IBD) and to define their clinical profile.
      The group consisted of 162 IBD patients of both sexes, aged 39-81 years, with 50
      healthy volunteers and 23 patients with other neurological diseases as control.
      Increased ACLA titer (above 0.9 GPL U/l IgG and 0.5 MPL U/l IgM) was registered
      in 17.9% IBD patients, and more frequently in patients with transitory ischemic
      attacks (TIA)-32.6%; slightly increased titer predominated (0.9-20 GPL U/l IgG
      and 0.5-15 MPL U/l IgM) in 69% IBD patients, while moderately increased (20-80
      GPL U/l and 15-50 MPL U/l IgM) was present in 21% IBD patients, while highly
      increased titer (above 80 GPL U/l IgG and above 50 MPL U/l IgM) was present in
      10.3%; IgG class was most frequently increased (9.2%), than IgM-5%, while
      increase of both classes was present in 3.7%. All patients with increased ACLA
      titer were below 50 years of age, had history of previous IBD attacks, more often
      TIA, irregularity of at least one coagulation test and fewer risk factors for
      IBD. Hence, increased ACLA titer was present in IBD patients of both sexes, below
      50 years of age with previous history of IBD attacks and fewer atherosclerosis
      risk factors.

PMID- 9623355
TI  - Anticardiolipin antibodies and clinical spectrum of antiphospholipid syndrome in
      patients with systemic lupus erythematosus.
AB  - In this paper we analyzed the clinical manifestation and course of the disease in
      47 patients with systemic lupus erythematosus (SLE) and secondary
      antiphospholipid syndrome (APS) during prospective follow-up that lasted 2-5
      years (mean 3.4). The most frequent features of APS were thrombosis (51%)
      thrombocytopenia (46.8%), and neuropsychiatric disorders (40.4%). These features
      were predominantly associated with elevated concentrations of IgG aCL isotype or
      with the presence of both IgG and IgM isotypes. Spectrum of neuropsychiatric
      disorders included mainly cerebrovascular ischemic disease (63%), but also some
      other, such as mental disorders and seizures, and, rarely, atypical migraine and
      transverse myelopathy. Thrombotic events in APS are the most significant for
      therapeutic and prognostic considerations. The treatment of basic disease (SLE)
      and conventional management of thromboembolic manifestation with heparin and/or
      dicoumarol (or warfarin) prevented neither the recurrent thrombosis in 9 patients
      (37.5%), nor the fatal outcome in 6 patients (12.8%). Further investigations and
      perhaps more aggressive approach to APS treatment are needed for better clinical
      care of these patients.

PMID- 9623356
TI  - Antiphospholipid syndrome in systemic connective tissue diseases.
AB  - Clinical manifestation and immunoserological features of secondary
      antiphospholipid syndrome (SAPS) were analyzed in this paper in 107 patients with
      systemic connective tissue diseases. In the group of patients with confirmed
      systemic lupus erythematosus (SLE), antiphospholipid antibodies (aPL) were
      positive in 43/93 (46.23%), while in 50/93 (53.76%) they were negative. Among aPL
      positive patients, 33/43 (76.74%) had clinical manifestations of SAPS, while 10
      patients (23.26%) were without any clinical manifestations. The most frequent
      manifestations of SAPS associated with SLE were: arteriovenous thrombosis in
      20/43 (46.51%), thrombocitopenia in 15/43 (34.88%) and autoimmune hemolytic
      anemia in 7/43 (16.27%). In our patients, rare manifestations of SAPS associated
      with SLE were recurrent fetal loss (1 case), livedo reticularis (1 case),
      transversal myelitis (2 cases), neuropathy (2 cases) and aseptic endocarditis
      (Libman-Sacks) (5 cases). Among 7 patients, with Sjogren's syndrome, clinically
      manifested SAPS was observed in 2, while in other 5 only increased aPL levels
      were found, as well as in patients with systemic vasculitis-3, MCTD-2 and Sy.
      Sjogren with vasculitis-1. One RA patient had thrombosis of v. cava inferior. In
      majority of patients with clinically present SAPS the levels of both examined
      immunoglobulin isotypes (IgG + IgM) were decreased-21/40 or 52.5%, while isolated
      increase of IgG was found in 14 (35%) and isolated increase of IgM in 5 (19.22%)
      patients. In three out of five patients with Libman-Sacks only LA test was
      positive. This investigation have shown that arterial and venous thromboses are
      the most common manifestations of SAPS in SLE. Every blood vessel may be involved
      (from arteriolae to the aorta and from postcapilar venules to the v. cava).

PMID- 9623357
TI  - Role of antiphospholipid antibodies in human reproduction.
AB  - The aim of this study was to evaluate the role of antiphospholipid antibodies
      (APA) in human reproduction. The investigation included 150 patients with
      systemic lupus erythematosus (SLE), and a group of 931 women, with the history of
      recurrent spontaneously miscarried pregnancies of unknown origin, even after a
      detailed examination in obstetric-gynecological institution. APA were
      investigated by means of tests to lupus anticoagulant (LA), applying a set of
      coagulation tests, including two tests with viper's poison, and cardiolipin
      antibodies (ACL) were determined by a standard immunoenzyme method, where a
      cardiolipin (Sigma, USA) was used as an antigen. The analysis of obstetric
      history in women with SLE has shown a considerable increase in frequency of
      obstetric complications in APA-positive group of patients (p < 0.001). Screening
      examination to APA, proved its presence in 254 of the total of 931 women (27%),
      and a complete evaluation of the positive group enabled the establishing of SLE
      diagnosis in 13 patients, in accordance with the valid criteria of the disease.

PMID- 9623358
TI  - The management of antiphospholipid syndrome.
AB  - This paper shows 21 patients with antiphospholipid syndrome, that were diagnosed
      after thrombosis, recurrent fetal loss or thrombocytopenia. Lupus anticoagulant
      was detected in 18, anticardiolipin antibodies in 15 and VDRL test was positive
      in 6 patients. Nine patients had recurrent venous thrombosis, 6 pulmonary
      embolus, 9 recurrent fetal loss and 15 were with low platelet count. Secondary
      prevention with oral anticoagulants was applied according to the level of INR 2.5
      3.5. Only one patient relapsed due to deficient anticoagulation. Three pregnant
      patients were treated with aspirin, and low molecular weight heparin, alone or in
      combination with prednisone. All of them had recurrent spontaneous abortions
      between 20 and 28 weeks of gestation. In conclusion, early diagnosis of
      antiphospholipid syndrome is very important. Secondary prevention of
      thromboembolic complications is recommended according to the level of INR > or =
      3. For the prevention of fetal loss we have not agreed upon treatment of all
      patients. Further studies are needed to define more precisely the optimal type,
      intensity, and the duration of therapy.

PMID- 9623359
TI  - Antiphospholipid antibodies in inflammatory bowel diseases.
AB  - Patients with inflammatory bowel diseases are susceptible to thrombosis in the
      active phase of the disease. Tests and some factors of coagulability have shown
      the existence of hypercoagulability of the blood in the active phase of these
      diseases. In the last few years some authors have found increased levels of
      antiphospholipid antibodies in the blood of patients with severe forms of Crohn's
      disease and ulcerative colitis. In a prospective study anticardiolipin antibodies
      have been measured in the blood of 12 patients, eight with ulcerative colitis and
      four with Crohn's disease. Six patients with ulcerative colitis and two with
      Crohn's disease were in the active phase of the disease, and the others in the
      remission. None of the patients had any clinical signs of thrombosis.
      Anticardiolipin antibodies were slightly increased in only one patient with
      severe ulcerative colitis complicated with erythema nodosum and swelling of the
      ankles. In nine patients anticardiolipin antibodies were in the normal range, but
      in two they were not found. Results of our study do not allow any definite
      conclusion regarding the possible role of antiphospholipid antibodies in the
      development of thrombosis in inflammatory bowel diseases: the number of the
      patients is relatively low and in half of the cases the disease was moderately
      active. Further studies are therefore necessary.

PMID- 9623360
TI  - [Rational for the use of human immunoglobulins in clinical practice].
AB  - The Clinic for Rheumatology and Clinical Immunology of the Military Medical
      Academy, with the participation of the hosts and experts from eminent Yugoslav
      institutions, in April 1997 organized the symposium on two current and trendy
      subjects from clinical immunology: "Antiphospholipid syndrome" and "The use of
      polyvalent intravenous immunoglobulins in the clinical praxis". This paper
      summarizes the contemporary knowledge about the structure and biological activity
      of immunoglobulins, methods for their production, different pharmacokinetic and
      pharmacodynamic characteristics of two types (5S and 7S) IVIG preparations, etc.
      We pointed out three basic groups of indications for IVIG clinical use: 1)
      substitutional therapy in the primary and secondary immunodeficiencies; 2)
      adjuvant therapy for severe infections; 3) immunomodulation in autoimmune
      diseases. Particular emphasis was put on currently known mechanisms of
      immunosuppressive action of IVIG in autoimmune diseases. Except for presently
      accepted indications for their use (idiopathic thrombocytopenic purpura and
      Kawasaki syndrome) we mentioned about 40 different diseases in hematology,
      neurology, rheumatology and other branches of medicine, from neonatology to
      transplantology, in which IVIG had shown some efficacy. Possibilities of
      different therapeutic modalities and the choice of diverse pharmacokinetic and
      pharmacodynamic effects, benefit the very wide spectrum of diseases, while
      minimal incidence of adverse effects suggested them to be the therapy of the
      future in the clinical practice.

PMID- 9623361
TI  - Intravenous immunoglobulin preparations as immunomodulatory agents.
AB  - Certain immunopathologic conditions, such as hypersensitivity and autoimmune
      diseases, are characterized by quantitative and/or qualitative alterations of
      immune reactions. It is now believed that such immunologic disturbances generate
      from inadequate internal control and regulation of immunologic reactivity.
      Important member of the complex regulatory network that supervises an immune
      response are antibodies themselves. Since antibody is bifunctional molecule, its
      regulatory action deals with two separate molecular structures denoted as Fab and
      Fc portion. By Fab fragment, antibody interferes with the reaction with antigens,
      or participates in the regulatory idiotype/antiidiotype interactions. Fc-mediated
      regulation includes influence on complement activation cascade, formation and
      clearance of immune complexes, phagocytosis, ADCC activity, T- and B-cell
      function, cytokine profile, etc. In general, antibody triggers immune reactions,
      but also has the capacity to suppress them. Exogenous antibodies are likely to
      elicit similar effects on immune processes. Actually, it has been demonstrated
      that intravenously given immunoglobulins, particularly high-dose IgG, effectively
      combat harmful immune response in some chronic inflammatory and autoimmune
      disorders. Hence, preparations of immunoglobulins for intravenous use (IVIG) can
      be considered as an immunomodulatory agent. To achieve the property of modulating
      the immune response, IVIG products must contain intact (7S) IgG molecule and
      maintain sufficient concentrations in plasma.

PMID- 9623362
TI  - High doses of immunoglobulins decrease mortality rate of surgical patients with
      severe intraabdominal infections and sepsis.
AB  - Two groups of 40 surgical Intensive Care Unit patients each, were included in the
      study. All patients had severe intraabdominal infections and sepsis, and septic
      score higher than 20. All were treated with individual specified conventional
      symptomatic therapy, and 40 of them received high doses of intravenous
      immunoglobulins. Significantly lower mortality rate was noticed in IVIG group
      (40%) than in control group (63.7%). Immunoglobulin therapy also decreased
      mortality rate in patients with septic shock, but it was no more effective than
      conventional therapy in patients with multiple organ failure (MOF).

PMID- 9623363
TI  - The significance of immunoglobulins in the treatment of patients with sepsis and
      septic shock.
AB  - Inappropriate body response is, besides the infectious agent, responsible for the
      genesis of sepsis and septic shock. It is non-specific and in cascade of events
      it can hardly be controlled. The results of immunoglobulins administration
      compared to the disease course and outcome have been compared and analyzed in 135
      patients with sepsis and septic shock. A hundred and four patients were treated
      for sepsis. Immunoglobulins were administered to 18, of whom 17 patients (94.55%)
      were cured, while one (5.55%) developed septic shock with lethal outcome. Out of
      the other 86 patients who did not receive immunoglobulins, 82 (95.35%) were
      cured, while in 4 (4.65%) patients the outcome was lethal. No difference was
      observed between studied groups. Among 31 patients with septic shock, 13 received
      immunoglobulins. Seven (53.85%) patients were cured, and 6 (46.15%) died. In
      relation to the favorable disease outcome the difference was observed
      (statistically non-significant) in the group that received immunoglobulins,
      compared to the group that did not (53.85% vs. 44.45%). The importance of
      immunoglobulins administration, in sepsis and septic shock should be emphasized.

PMID- 9623365
TI  - Society for Epidemiologic Research 31st annual meeting. Chicago, Illinois, USA.
      June 24-26, 1998. Abstracts.

PMID- 9623364
TI  - Treatment of IgA nephropathy with nephrotic syndrome using pulse doses of IgG.
AB  - This paper presents the preliminary results of the treatment of nephrotic
      syndrome in IgA nephropathy (IgAN) using pulse doses of IgG. Diagnosis was
      established only by percutaneous ultrasonically-guided renal biopsy, as well as
      on the basis of typical immunofluorescence and light microscopy findings.
      Histopathologic changes were classified according to the World Health
      Organization classification for IgAN, by determination of average glomerular,
      vascular and interstitial fibrosis indices and the degree of tubular atrophy. IgG
      therapy was administered in three patients with nephrotic syndrome associated
      with IgAN characterized by minimal histological changes, i.e., by diffuse
      mesangioproliferative glomerulonephritis. Initial IgG pulse dose was 0.4 g/kg,
      given as slow intravenous infusion during three consecutive days in the course of
      the three-month period. Maintenance therapy consisted of intramuscular IgG in the
      doses of 2.5 g twice a month, for the next three months. After a six-month
      treatment, clinical and biochemical remission was achieved in patients with
      minimal histologic changes, but in other two patients with diffuse
      mesangioproliferative glomerulonephritis, the effect of the therapy consisted of
      reduced proteinuria by more than 50%, with the renal function restored to the
      level before therapy. Transient increase in the serum creatinine level was found
      in two patients. These preliminary results with IgG pulse therapy, although
      obtained on a small number of patients, suggest the drug's potent
      immunomodulatory properties, but its complexity and levels of actions should be
      further investigated.

PMID- 9623366
TI  - Transplantation in Hematology and Oncology. Munster, Germany, 10-12 May 1998.
      Abstracts.

PMID- 9623367
TI  - Radiology 1998--Imaging, Science and Oncology. Birmingham, United Kingdom, 1-3
      June 1998. Abstracts.

PMID- 9623368
TI  - Pathological Society of Great Britain and Ireland, 176th meeting. London, United
      Kingdom, 7-9 January 1998. Abstracts.

PMID- 9623369
TI  - Surgical history. The history and evolution of surgical instruments. VIII.
      Catheters, hollow needles and other tubular instruments.

PMID- 9623370
TI  - Frostbite: epidemiology at high altitude in the Karakoram mountains.
AB  - During a 10-year period (December 1984 to December 1994), 1500 cases of frostbite
      were treated at a tertiary care medical facility. They were all males with their
      ages ranging from 17 to 43 years. All the patients sustained the frostbite injury
      in the northeastern part of Pakistan known as the Karakoram range of mountains.
      They included a large number of porters and guides employed by various
      mountaineering expeditions (approximately 250-300 expeditions per year) in that
      region, as well as local inhabitants. This retrospective study included the
      heights at which frostbite occurred (range 11,000-22,000 feet above sea level).
      Of the patients, 15% (n = 225) got frostbitten within 1 h of exposure, whereas
      the majority (71%) had an exposure of 1-3 h. The effect of seasonal variations
      (relative hypothermia) on the extent and depth (degree) of frostbite and the
      distribution of lesions as per body surface subunits (areas) was noted and found
      to be statistically significant with P < 0.05 for both. The occurrence of
      frostbite at various heights showed a very steep upward curve beyond a height of
      17,000 feet above sea level. This has been termed the 'cut-off' point for
      frostbite by the authors, the increase depicting the true picture of 'high
      altitude frostbite'. Tobacco smoking and peripheral vascular disease were found
      to be important contributing factors. The feet were involved most frequently
      (64%) followed by the hands (32%), the head and neck region (3%) and the perineum
      (1%). Independent effects of the height (relative hypoxia) on the depth of
      frostbite lesion (degree) and on the involvement of multiple body areas (surface
      subunits) showed significant correlation with P values well below 0.05 for each.
      Of cases, 92% (n = 1386) had second- or third-degree frostbite necessitating
      definitive surgical intervention. Total frostbite-related mortality spanned over
      10 years was 11%.

PMID- 9623371
TI  - Photoplethysmography can replace hand-held Doppler in the measurement of
      ankle/brachial indices.
AB  - Ankle/brachial pressure index (ABPI) using hand-held Doppler and sphygmomanometer
      is a standard assessment for patients with peripheral arterial occlusive disease
      (PAOD). Good Doppler technique is difficult to master and so we investigated
      replacing Doppler with photoplethysmography (PPG). Two investigators examined 52
      legs in 32 vascular patients. Both used standard sphygmomanometer cuff occlusion.
      Restoration of flow was detected by either an 8 MHz Doppler ultrasound probe or a
      PPG transmitter/receiver on index finger or great toe. Doppler-derived ABPIs were
      compared with PPG-derived ABPIs. Excellent correlation was found between both
      indices (correlation coefficient 0.875). Four lower limbs had unrecordable PPG
      traces, one also having an unrecordable Doppler signal. Excluding these four
      patients, the correlation coefficient rose to 0.975. PPG placed on the pulp of a
      digit can replace the hand-held Doppler in measuring ABPIs.

PMID- 9623372
TI  - Distal amputations: impact of the introduction of femorocrural and femoropedal
      arterial bypass.
AB  - The aim of the study was to assess the impact of the introduction of femorodistal
      arterial bypass grafting on the patterns of lower limb amputation and
      reconstructive surgery, in particular the success rates of distal, conservative,
      amputations. Two 2-year cohorts of patients 7 years apart were analysed by a
      retrospective analysis of departmental audit and patient records. Significantly
      more patients undergoing distal amputation were considered to have
      reconstructible arterial disease in the later cohort. This was paralleled by an
      increase in the rate of suprapopliteal/popliteal and distal arterial bypass and a
      fall in below-knee amputation rate in this group of patients. The overall healing
      rate and rate of conversion of distal amputations were not adversely affected by
      the introduction of femorodistal bypass grafting, despite the fact that more
      distal amputees were non-diabetic in this second group. There was a high rate of
      success for distal amputations combined with femorodistal bypass, but the
      subgroup was too small for statistical analysis. We conclude that the use of
      distal amputation, with or without distal arterial bypass, offers a promising,
      although unproven, prospect for lower limb conservation even in non-diabetics.

PMID- 9623373
TI  - Subfascial endoscopic perforator vein surgery (SEPS): current practice among
      British surgeons.
AB  - Subfascial endoscopic perforator vein surgery (SEPS) has recently caused
      considerable interest among British surgeons. There are no data indicating which,
      if any, patients benefit from SEPS. A series of 47 British surgeons, identified
      as having taken up SEPS, were sent a questionnaire asking about their current
      practice; 26 were returned completed (55% response rate). Of those surgeons
      replying, 22 (85%) had performed their first SEPS procedure within the previous
      21 months, 18 (69%) within the previous 9 months. Most surgeons had performed
      five procedures (range 1-52). The most common indication for SEPS was venous
      ulceration with proven incompetent perforators (eight surgeons), but there was a
      wide diversity of other indications used to select patients for SEPS. Only nine
      surgeons had changed their indications for surgery with the advent of SEPS, yet
      their predicted number of SEPS procedures was far greater than the number of open
      procedures they currently performed. Out of 26 surgeons, 25 intend to continue
      performing SEPS. Prospective studies are needed to identify which patients might
      benefit from this new procedure.

PMID- 9623374
TI  - Day-case oral and maxillofacial surgery in a Nigerian district general hospital:
      scope and limitations.
AB  - Day-case surgery is becoming attractive worldwide to various surgical
      specialties, but there are few reports from West Africa. Between January 1987 and
      January 1997, 2980 patients who attended an oral and maxillofacial unit were
      operated on as day cases. This represents 65% of the 4585 patients who had oral
      and maxillofacial surgery during this period. Of these patients, 362 (12.15%) had
      general anaesthesia, while 2618 (87.85%) accepted local anaesthesia. Readmission
      is a failure of day-case surgery. In this series, it was due to bleeding in 80 of
      102 cases of excision of submandibular salivary gland adenoma. We believe that
      day-case oral and maxillofacial surgery is safe and effective, but that caution
      should be exercised when operating on benign submandibular salivary gland
      neoplasms under general anaesthesia.

PMID- 9623375
TI  - Appropriate use of the day care unit for rigid endoscopy of the upper
      aerodigestive tract.
AB  - There is increasing pressure for more day surgery to be undertaken in the health
      service. In this retrospective study of 325 rigid upper aerodigestive tract
      endoscopies performed in the Day Care Unit of The Royal National Throat Nose and
      Ear Hospital, London, there were no post-discharge complications and only four
      patients required admission, none were, in our opinion, the direct result of day
      case rigid endoscopy. In our unit, the day case rate for microlaryngeal surgery
      is 44.8%, showing that rates significantly higher than published national rates
      of 17.1% (1993/1994) are achievable. We conclude that day case microlaryngeal
      surgery and diagnostic rigid endoscopy of the upper aerodigestive tract is safe
      if performed by suitably qualified staff in dedicated specialist units with
      patients selected according to existing day case criteria.

PMID- 9623376
TI  - Iatrogenic oesophageal perforations: a clinical review.
AB  - Thirty patients with iatrogenically induced perforation of the oesophagus were
      managed in our unit between January 1986 and December 1996. Thirteen (43%) of
      these injuries were referred after upper gastrointestinal endoscopy performed by
      physicians. Ten (33%) cases were referred by ENT surgeons and general surgeons
      referred 7 (23%) cases. Of these patients, 15 (50%) had no abnormality of the
      oesophagus found before perforation. Only 18 (60%) of patients were referred
      within 24 h of injury. The mean duration of care required in the intensive care
      unit was 1.5 days +/- 2.5 days and the mean inpatient hospital stay 26.5 days +/-
      22.1 days. The mortality was 10% (three cases). Oesophageal perforation remains a
      serious life-threatening injury. The early diagnosis of this uncommon condition
      requires a high index of suspicion as the symptoms are often non-specific.
      Identification of the site of perforation is necessary as the management of
      cervical and thoracic perforations differs considerably. Early referral combined
      with appropriate therapy would appear to result in a better outcome than
      previously published data. It is therefore suggested that patients with this
      relatively rare condition should be referred as soon as possible to a centre with
      expertise in its management.

PMID- 9623377
TI  - Laparoscopic cholecystectomy, bile duct injury and the British and Irish surgeon.
AB  - Laparoscopic cholecystectomy continues to attract controversy with regard to a
      perceived higher incidence of bile duct injury than in the open procedure. One
      possible cause for this is the trend away from intraoperative cholangiography
      previously considered an essential part of the open procedure. Under the auspices
      of The Association of Surgeons of Great Britain and Ireland, a questionnaire was
      sent to all its consultant fellows asking for details about their individual
      experience of the most serious injury, bile duct resection. In all, 1100
      questionnaires were sent; 362 (33%) replies were returned. Of those who replied,
      300 performed laparoscopic cholecystectomy as part of their practice. The
      experience of the respondents was divided into three groups; 19 surgeons had
      performed < 50 laparoscopic cholecystectomies, 53 between 50 and 100 and 228 had
      performed over 100. Ninety-five (32%) never performed intraoperative
      cholangiography, 167 (56%) on a selective basis and 38 (12%) routinely. In all,
      58 bile duct resection injuries were reported by 48 surgeons. Of the bile duct
      resection injuries reported, 49 of 58 (85%) occurred when an intraoperative
      cholangiogram was not performed. These figures suggest that if the incidence of
      bile duct resection injury is to be decreased in laparoscopic cholecystectomy,
      the use of intraoperative cholangiography has an integral role to play.

PMID- 9623378
TI  - Is the incidence of acute appendicitis really falling?
AB  - To determine if there has been a genuine fall in the incidence of acute
      appendicitis, an epidemiological study using HAA and Korner datasets for the
      years 1975-1994 was carried out to identify those children and young adults
      undergoing appendicectomy for acute appendicitis. The overall incidence of acute
      appendicitis fell from 1.84/1000 to 1.17/1000. This fall was statistically
      significant (R2 = 0.74, P < 0.01). The decrease was significant in both males
      (overall reduction, 34%) and females (overall reduction, 40%). No significant
      reduction was observed in either males or females between 15 and 19 years of age.
      The overall reduction remains essentially unexplained, but may have implications
      for health planning and provision of services.

PMID- 9623379
TI  - Metabolic and inflammatory responses after laparoscopic and open inguinal hernia
      repair.
AB  - A prospective comparison of metabolic and inflammatory responses after
      laparoscopic and open inguinal hernia operations was undertaken. There were 10
      patients in each group. Plasma levels of cortisol, growth hormone, prolactin, C
      reactive protein (CRP) and interleukin-6 (IL-6) were measured preoperatively and
      at fixed intervals up to 120 h postoperatively. In vitro, endotoxin stimulated
      whole blood tumour necrosis factor alpha (TNF alpha) was measured in preoperative
      and 24 h postoperative blood samples. Changes in the plasma levels of cortisol,
      growth hormone and prolactin showed no statistically significant difference
      between the groups. No significant change in IL-6 levels were recorded in any
      group. Changes in CRP levels were significantly higher (P < 0.006) in open hernia
      patients. Endotoxin stimulated TNF alpha production was suppressed in both
      groups. The degree of suppression in open hernia patients was significantly
      higher (P < 0.005). This study has shown that both these operations produce
      similar stress responses. However, open hernia operation results in a higher
      acute phase response and induces a greater endotoxin tolerance.

PMID- 9623380
TI  - 'One-stop' rectal bleeding clinics without routine flexible sigmoidoscopy are
      unsafe.
AB  - Over 90% of patients referred to surgeons for investigation of rectal bleeding
      have haemorrhoids, fissure-in-ano or proctitis. Full investigation of these
      patients to exclude colonic neoplasia or inflammatory bowel disease imposes a
      considerable load on a hospital's resources as well as exposing the patient to
      significant inconvenience and morbidity. A 'one-stop' outpatient clinic was
      established, with selective use of flexible sigmoidoscopy, based on the judgement
      and clinical findings of a single experienced surgeon. Over a 4 month period, 344
      patients were assessed, and 326 were identified as not needing flexible
      sigmoidoscopy. At 3 and 6 monthly follow-up, 22 presented with persistent rectal
      bleeding and three previously unidentified cancers were found on performance of
      flexible sigmoidoscopy. If a 'one-stop' policy is to be used in the management of
      rectal bleeding, routine flexible sigmoidoscopy is essential for all patients.

PMID- 9623381
TI  - Posterior sagittal proctectomy.
AB  - Rectal excision for non-malignant conditions using a posterior sagittal approach
      is described in three patients. The technique allows excellent exposure of the
      rectum, meticulous haemostasis, minimal risk of pelvic nerve injury and accurate
      reconstruction of the pelvic floor without the need for drainage.

PMID- 9623383
TI  - Day-case or short-stay admission for arthroscopic knee surgery: a randomised
      controlled trial.
AB  - The Royal Colleges, The Audit Commission, and politicians have encouraged day
      case care for patients undergoing arthroscopic knee surgery. However, there
      remains both public and professional concern regarding the acceptability and
      safety of this form of management, although there are clear economic benefits. In
      a prospective randomised controlled trial, 50 patients underwent arthroscopic
      surgery as a day-case and 50 patients were admitted overnight. Outcome was
      assessed by postal questionnaire 4 weeks after discharge. A linear visual
      analogue scale was used to measure pain levels. The response rate was 93%. The
      diagnoses and types of arthroscopic surgery were similar in both groups. In
      total, 94% of day-cases and 91% of patients admitted overnight expressed overall
      satisfaction. Pain after discharge was similar in both groups. Day-case
      management was preferred by 90% of day-case patients and by 64% of those admitted
      overnight. Of patients in the day-case group, 12% had to be admitted overnight
      because of recovery problems, but 7% of patients randomised to overnight stay
      discharged themselves. One patient admitted overnight required readmission
      because of a wound haematoma. Patients who had received day-case management
      returned to work significantly faster than those who had been admitted. Modern
      anaesthetic techniques with special attention to anti-emesis and pain control
      have reduced postoperative morbidity to acceptable levels. Provided that patients
      are properly selected and well informed, day-case care is preferable for the
      majority of patients undergoing arthroscopic surgery of the knee.

PMID- 9623382
TI  - Nitric oxide synthase neurones and neuromuscular behaviour of the anorectum.
AB  - Intensive research into the biological roles of nitric oxide has shown that this
      tiny molecule is of vital physiological significance in numerous organ systems
      including the gastrointestinal tract, where nitric oxide has been proposed as an
      inhibitory enteric neurotransmitter. This paper outlines experiments using
      retrograde neuronal tracing and enzyme histochemistry in a guinea-pig model which
      provided the first direct anatomical evidence of a descending nitrergic rectoanal
      neuronal pathway appropriate to mediating relaxation of the internal anal
      sphincter during the rectoanal inhibitory reflex. Studies of human tissue showed
      that the in vitro responses of isolated strips of human rectum were typical of
      non-sphincter specialized gastrointestinal smooth muscle, that nitric oxide is
      involved in neurogenic relaxation of the rectum and that nitric oxide synthase
      immunocytochemistry identified a subpopulation of neurones in the myenteric
      ganglia and immunoreactive profiles within both layers of the muscularis propria
      of human rectum. Taken together, these data provide pharmacological and
      anatomical support for the hypothesis that nitric oxide acts as a functionally
      important mediator in the innervation of human anorectum.

PMID- 9623384
TI  - Allograft bone transplantation: a Sheffield experience.
AB  - There has been an increase in demand for allograft bone in recent years. This
      type of bone provides an excellent material to fill in bony defects, but could be
      associated with an incidence of infection. Any newly established tissue bank has
      to meet the very stringent criteria to process and store bone and maintain a
      donor and recipient database to avoid transmission of infection. The Sheffield
      Tissue Bank has been functioning since 1989 and until 1993 has provided bone
      allografts to 220 patients; these have been used mainly to reconstruct defects at
      revision hip and knee arthroplasty and for scoliosis surgery. There have been no
      cases of disease transmission and the rate of infection has been reduced by
      strict screening protocols. This paper outlines our experience, problems and
      success with human bone banking.

PMID- 9623385
TI  - Fine-bore cannulas for peripheral intravenous nutrition: polyurethane or
      silicone?
AB  - The peripheral intravenous route is being used more frequently for the
      administration of short- to medium-term parenteral nutritional support. Dedicated
      fine bore cannulas have significantly reduced the incidence of thrombophlebitis.
      Currently available cannulas are made of polyurethane or silicone. We present our
      experience with a 23G silicone cannula and a 22G polyurethane alternative. Fifty
      four silicone cannulas were used with a median survival of only 3 days, compared
      with 7 days for 90 polyurethane cannulas (P < 0.0001). Only 22% of silicone
      cannulas were removed electively compared with 56% of polyurethane cannulas (P <
      0.00005). The most common cause for silicone cannula removal was occlusion (48%),
      which occurred in only 8% of polyurethane cannulas (P < 0.00001). Polyurethane
      cannulas develop fewer complications and are more effective in the delivery of
      peripheral intravenous nutritional support.

PMID- 9623386
TI  - 'What's the serum albumin?'.

PMID- 9623387
TI  - How long should suction drains stay in after breast surgery with axillary
      dissection?

PMID- 9623388
TI  - Reconstruction of the iliofemoral venous circulation using internal jugular vein
      autograft.

PMID- 9623389
TI  - Good enough parenting for all children--a strategy for a healthier society.

PMID- 9623390
TI  - Genetic aspects of Charcot-Marie-Tooth disease.

PMID- 9623391
TI  - Systematic review of the school entry medical examination.
AB  - AIMS: To summarise and critically evaluate research conducted in the UK between
      1962 and 1996, on the effectiveness and efficiency of the school entry medical
      (SEM) examination. METHODS: An electronic search of a large number of databases,
      in conjunction with a search of reference lists, and sources in the grey
      literature produced a total of 64 studies. RESULTS: Only one overview and 16
      primary studies met the review's broad inclusion criteria. The results showed
      significant differences in the identification and referral of new and ongoing
      problems not only between the routine and selective SEM but also within the two
      types of SEM examination. There were also large differences in the numbers of
      children selected for SEM examination. No study included in the review defined
      either the methods or the criteria used to identify children as screen positive.
      No study provided follow up of children after referral to estimate the positive
      predictive value or yield of the screening, or follow up of the whole cohort to
      identify false negative cases. CONCLUSION: Data on the effectiveness and
      efficiency of both the routine and selective SEM examination in accurately
      identifying children with new or ongoing health problems are not available at the
      present time. The studies reviewed here demonstrate the fragility of the evidence
      on which the school entry medical is based, and call into question the ethical
      basis of this programme.

PMID- 9623392
TI  - Survey of UK computerised special needs registers.
AB  - A postal survey of all computerised children's disability registers in the UK was
      undertaken in 1996. Information was returned from 155 of 166 districts (93%). The
      implementation of computerised special needs registers is a continuing nationwide
      trend. Although there is evidence of successful use of registers both as an
      individual and as a population service planning tool, a high percentage of
      existing registers are functioning in a way which is far short of their potential
      for research, audit, and planning. Registers which work well have been set up
      with expertise, have staff enthusiastic about data entry, and are well supported
      for data output and software modification. There should be continued cooperative
      work towards a national consensus on the categories of disability and definition
      of severity of disability used in these registers.

PMID- 9623393
TI  - Congenital central hypoventilation syndrome and Hirschsprung's disease.
AB  - Five cases of the Hirschsprung's disease-congenital central hypoventilation
      syndrome (CCHS) association are presented and 41 other published cases reviewed.
      These children have a distinct pattern of associated features, an equal sex
      incidence, and a characteristic spectrum of disease severity which suggests that
      the condition is genetically distinct from other cases of Hirschsprung's disease.
      While approximately 1.5% of Hirschsprung's disease patients, and 10% of those
      with total colonic aganglionosis, will have CCHS, up to 50% of CCHS patients will
      have Hirschsprung's disease. Approximately 20% of CCHS/Hirschsprung patients will
      also have neuroblastoma or ganglioneuroma, usually multiple. Abnormalities of the
      eye and autonomic nervous system are also common. The ventilatory abnormality is
      usually evident on the first day of life. The aganglionosis is also severe, with
      more than half (59%) of the patients having aganglionosis extending into the
      small bowel.

PMID- 9623394
TI  - Mechanical model testing of rebreathing potential in infant bedding materials.
AB  - Rebreathing of expired air may be a lethal hazard for prone sleeping infants.
      This paper describes a mechanical model to simulate infant breathing, and
      examines the effects of bedding on exhaled air retention. Under simulated
      rebreathing conditions, the model allows the monitoring of raised carbon dioxide
      (CO2) inside an artificial lung-trachea system. Resulting levels of CO2 (although
      probably exaggerated in the mechanical model compared with an infant, due to the
      model's fixed breathing rate and volume) suggest that common bedding materials
      vary widely in inherent rebreathing potential. In face down tests, maximum airway
      CO2 ranged from less than 5% on sheets and waterproof mattresses to over 25% on
      sheepskins, bean bag cushions, and some pillows and comforters. Concentrations of
      CO2 decreased with increasing head angle of the doll, away from the face down
      position. Recreations of 29 infant death scenes also showed large CO2 increases
      on some bedding materials, suggesting these infants could have died while
      rebreathing.

PMID- 9623396
TI  - Car restraints and seating position for prevention of motor vehicle injuries in
      Greece.
AB  - The protective effect of child restraint and the relative safety of front and
      rear seating in a population where children often travel unrestrained was
      assessed in a population based case-control study. The cases were all 129
      children aged 0-11 years injured as car passengers in a motor vehicle accident
      who contacted, during 1996, one of the two major children's hospitals in Athens;
      emergency cases are accepted by the two hospitals on alternate days throughout
      the year, thus generating a random sample of children injured as car passengers.
      The prevalence of the studied exposures in the study base was estimated from an
      inspection survey comprising a random sample of 191 children of the same age who
      travelled in passenger cars. The survey was conducted by medical staff from our
      centre in collaboration with the road traffic police. Odds ratios (ORs) were
      calculated after adjustment for confounding factors through the Mantel-Haenszel
      procedure. The OR for injury was 3.3 among unrestrained children compared with
      restrained children (comparison essentially limited to children aged 0-4 years)
      and 5.0 for children seated in the front compared with those seated in the rear
      (comparison essentially limited among unrestrained children). Protective effect
      estimates derived from this analytical study suggest that in Greece about two
      thirds of all childhood injuries from car crashes could have been avoided through
      the regular use of a proper child restraint. The data also indicate that, in the
      absence of a child restraint system, a rear seating position conveys substantial
      protection and could explain the low mortality of children as car passengers in
      Greece, a country which is characterised by a high overall road traffic mortality
      as well as a high childhood accident mortality.

PMID- 9623395
TI  - A case-control study of smoking and sudden infant death syndrome in the
      Scandinavian countries, 1992 to 1995. The Nordic Epidemiological SIDS Study.
AB  - AIM: To establish whether smoking is an independent risk factor for sudden infant
      death syndrome (SIDS), if the effect is mainly due to prenatal or postnatal
      smoking, and the effect of smoking cessation. METHODS: The analyses were based on
      data from the Nordic epidemiological SIDS study, a case-control study with 244
      cases and 869 controls. Odds ratios were computed by conditional logistic
      regression analysis. RESULTS: Smoking emerged as an independent risk factor for
      SIDS, and the effect was mainly mediated through maternal smoking in pregnancy
      (crude odds ratio 4.0 (95% confidence interval 2.9 to 5.6)). Maternal smoking
      showed a marked dose-response relation. There was no effect of paternal smoking
      if the mother did not smoke. Stopping or even reducing smoking was beneficial.
      SIDS cases exposed to tobacco smoke were breast fed for a shorter time than non
      exposed cases, and feeding difficulties were also more common. CONCLUSIONS:
      Smoking is an independent risk factor for SIDS and is mainly mediated through
      maternal smoking during pregnancy. Stopping smoking or smoking less may be
      beneficial in reducing the risk of SIDS.

PMID- 9623397
TI  - Development and evaluation of an information booklet for adult survivors of
      cancer in childhood. The United Kingdom Children's Cancer Study Group Late
      Effects Group.
AB  - AIMS: To determine the need for information among survivors of childhood cancer,
      to assess the acceptability of an information booklet, and to investigate the
      effectiveness of the booklet in increasing knowledge and influencing health
      related behaviours. SUBJECTS: Fifty survivors of childhood cancer (age range 14
      32 years) who were consecutive attendees at a long term follow up clinic.
      METHODS: The booklet was developed for young people aged 14 years and above by
      the United Kingdom Children's Cancer Study Group Late Effects Group. Included is
      information about treatment of cancer, general advice about a healthy lifestyle,
      the rationale for long term follow up, and information about employment and life
      insurance problems. Survivors were interviewed at the follow up clinic, offered
      the booklet, and contacted approximately one week later for a telephone
      interview. The clinic interview assessed survivor's understanding of their
      illness and treatment and its impact on their lives, and their preferences for
      further information. The telephone interview determined survivors' general
      reaction to the booklet, whether it increased knowledge and influenced health
      related behaviours. RESULTS: All those interviewed accepted the written
      information and agreed to a follow up interview. Survivors were enthusiastic
      about being given more information. Over three quarters learned new information
      from the booklet. There were no indications that the information was associated
      with anxiety for any demographic or clinical subgroups. After reading the booklet
      there was an increased awareness of the risk from sunbathing (p < 0.05), and
      greater appreciation of the importance of follow up (p < 0.05). CONCLUSIONS:
      These results suggest that written information is likely to be an acceptable and
      effective supplement to discussions with medical professionals and may readily be
      incorporated into long term follow up clinics.

PMID- 9623398
TI  - Influence of five years of antenatal screening on the paediatric cystic fibrosis
      population in one region.
AB  - BACKGROUND: Antenatal screening for cystic fibrosis has been endorsed by the US
      National Institutes of Health. Edinburgh is the only city in the UK with an
      established routine antenatal screening programme for cystic fibrosis. AIMS: To
      report the change in numbers of infants diagnosed with cystic fibrosis born in
      Edinburgh after the introduction of antenatal screening for the disease.
      POPULATION: Infants diagnosed as having cystic fibrosis (by sweat test or
      genotyping, or both) in the seven years before antenatal testing (1984-90) and
      the first five years of antenatal testing (1991-95). Children born in this region
      who had moved before diagnosis were identified from the UK cystic fibrosis survey
      database. RESULTS: The incidence of cystic fibrosis decreased from an average of
      4.6 to 1.6 children each year with antenatal screening. The reduction in the
      incidence (65%) was greater than that accounted for by prenatal diagnosis and
      termination (36%). Of the eight children born with cystic fibrosis during the
      period of antenatal screening, five had been subject to antenatal screening:
      three had only one mutation identified, one was missed due to a laboratory error,
      and one was identified as a one in four risk, but prenatal diagnosis was not
      performed. CONCLUSIONS: Antenatal testing for cystic fibrosis has successfully
      reduced the incidence of cystic fibrosis in this region. Although the numbers are
      small, it is possible that the reduction in numbers may have been greater than
      might be expected from antenatal screening alone.

PMID- 9623399
TI  - Management of tuberculosis in Wales: 1986-92.
AB  - OBJECTIVES: To describe the epidemiology of childhood tuberculosis in Wales and
      to assess the standard of management of patients with tuberculosis. DESIGN:
      Retrospective study of data retrieved from case notes and review of radiographs
      of all identified patients. SUBJECTS: Forty eight cases of tuberculosis and 10 of
      tuberculosis chemoprophylaxis in children under 15 years of age, in Wales,
      between January 1986 and December 1992. MAIN OUTCOME MEASURES: Management of
      childhood tuberculosis in Wales compared with the published recommendations of
      the Joint Tuberculosis Committee of the British Thoracic Society. RESULTS:
      Documentation was poor in most of the 48 cases of tuberculosis and only 31 (65%)
      were formally notified. One third of patients were asymptomatic and were detected
      by contact tracing; only eight (17%) were culture positive. Only 20% of patients
      from ethnic minorities had previously been immunised with BCG. Management and
      chemotherapy varied widely. Few patients were managed jointly by paediatricians
      and chest doctors. Only 10% completed treatment with a recommended chemotherapy
      regimen. In 37% of patients treatment was inadequate, and in the remainder either
      the choice of drugs or the duration of treatment was inappropriate. No patient
      died, nor had any relapsed by June 1995. CONCLUSIONS: Very few cases of childhood
      tuberculosis were managed according to the recommendations of the British
      Thoracic Society.

PMID- 9623400
TI  - The need for revised standards for skinfold thickness in infancy.
AB  - Skinfold standards provide a useful indication of subcutaneous fat. To evaluate
      skinfold thickness of 252 Cambridge infants over the first 2 years of age, SD
      scores relative to the Tanner standards were calculated, taking account of
      skewness in the standards. Cambridge SD scores were low, varying according to age
      from -1.2 to -1.8 for triceps and -0.6 to -1.2 for subscapular skinfolds. The
      Tanner skinfold standards were last revised 30 years ago, at a time of high
      prevalence of infantile obesity, and the present and other studies indicate that
      infants are now thinner. There is a need for new skinfold standards to reflect
      this change. Since the Cambridge infants contributed to the recent British height
      and weight references, it is suggested that their skinfold measurements could
      also serve as reference points.

PMID- 9623401
TI  - Intra-arterial calcium stimulation test in the investigation of hyperinsulinaemic
      hypoglycaemia.
AB  - OBJECTIVE: To investigate the use of a calcium infusion test in the diagnosis and
      localisation of insulin secreting tumours in children. PATIENTS: Three patients
      with persistent hypoglycaemia of infancy (PHHI). PROCEDURE: During planned
      selective coeliac and mesenteric arteriography, serial samples were taken from a
      catheter in the right hepatic vein for insulin measurement following the
      injection of calcium gluconate. RESULTS: In all three children, selective intra
      arterial calcium stimulation produced a significant rise in plasma insulin and
      was of value in localising the pancreatic abnormality in one child. In vitro
      studies on islets of Langerhans isolated from this patient following partial
      pancreatectomy showed unresponsive intracellular calcium signalling of the cells
      when stimulated with high extracellular concentrations of glucose and potassium
      or with sulphonylurea drugs (tolbutamide), but normal responsiveness to
      increasing extracellular calcium concentrations. CONCLUSIONS: The findings
      suggest a functional abnormality of the calcium channel in PHHI and provide a
      rationale for the reported efficacy of channel blocking drugs in this condition.
      The role of selective intra-arterial calcium stimulation in the diagnosis of
      hyperinsulinaemic hypoglycaemia in childhood warrants further investigation.

PMID- 9623402
TI  - A survey of paediatricians' practice and training in routine infant eye
      examination.
AB  - A survey of a sample of UK paediatricians was carried out to identify the
      practices and determine the training of those involved in routine surveillance
      examinations to detect ophthalmic disorders in infants. The findings indicate
      important variation in current practices and raise concerns about both
      undergraduate and postgraduate training in ophthalmic assessment of infants.

PMID- 9623403
TI  - Arthritis as a presenting feature of non-Hodgkin's lymphoma.
AB  - Leukaemia can present with joint swelling in the absence of abnormal
      haematological findings. Arthritis as a presenting sign of lymphoma, however, is
      extremely rare. Three children with non-Hodgkin's lymphoma who had joint swelling
      at the onset of their disease are reported. Two cases showed histological
      features of anaplastic large cell lymphoma (Ki-1/CD30 positive), and one of
      angioimmunoblastic T cell lymphoma. In all patients the unusual presentation
      delayed correct diagnosis.

PMID- 9623404
TI  - Hereditary CD4+ T lymphocytopenia.
AB  - Two siblings suffering from mental retardation, progressive bronchiectasis,
      extensive warts, and persistent hepatitis B are described. The propositus also
      had an unusual physiognomy and non-specific colitis. Both patients had a marked
      decrease in the population of CD4+ helper T cells.

PMID- 9623405
TI  - Predominant enteroviral serotypes causing meningitis.
AB  - All enteroviral reports to the Public Health Laboratory Service from 1975 to 1994
      which had been proved by culture were analysed. Of the 40,366 isolates, 5741
      reports (14%) were from cultures of cerebrospinal fluid. The groups and serotypes
      accounting for the largest number of cerebrospinal fluid isolates were A9, E7,
      E9, E11, E19, and E30, accounting for 70% of all cultured isolates of
      cerebrospinal fluid. It may be possible to prevent most cases of viral meningitis
      in the UK with the development of an enteroviral vaccine.

PMID- 9623406
TI  - Oesophageal atresia, VACTERL association: Fanconi's anaemia related spectrum of
      anomalies.
AB  - Oesophageal atresia usually occurs without any genetic background. Three cases
      associated with Fanconi's anaemia are reported. One neonate had growth
      retardation and numerous malformations including oesophageal atresia and four
      other components of the VACTERL association. In the two others, oesophageal
      atresia was isolated. In patients with such malformations an early diagnosis of
      Fanconi's anaemia may have important genetic and therapeutic implications.

PMID- 9623407
TI  - Maintenance of growth in cystic fibrosis despite reduction in pancreatic enzyme
      supplementation.
AB  - Twenty one children with cystic fibrosis were advised to decrease their
      pancreatic enzyme supplement (PES) dose to less than 10,000 units lipase/kg/day.
      Mean PES dosage was significantly decreased in 15 patients from 18,380 to 8647
      units lipase/kg/day. There were no significant changes in energy or fat intake,
      but there were significant increases in weight SD score, height SD score, and
      weight/height ratio.

PMID- 9623408
TI  - Agreement on responses to respiratory illnesses questionnaire.
AB  - The prevalence of respiratory symptoms and illnesses among 2225 schoolchildren in
      Hong Kong was studied by questionnaires administered independently to them and
      their parents. The agreement was generally poor for respiratory symptoms. The
      disparity shows the need for cross validation of clinical information in history
      taking.

PMID- 9623409
TI  - Epidemiology of visual impairment in Britain.

PMID- 9623410
TI  - Mitochondrial disorders and the kidney.

PMID- 9623412
TI  - Asthma--time for a change of name?

PMID- 9623411
TI  - Advances in childhood onset diabetes.

PMID- 9623413
TI  - Rapid response to isoflurane in refractory status asthmaticus.

PMID- 9623414
TI  - Whole body bone mineral content in healthy children and adolescents.

PMID- 9623415
TI  - Diurnal variation in children: is stretching the answer?

PMID- 9623416
TI  - Oral testosterone undecanoate for the induction of puberty in anorchid boys.

PMID- 9623417
TI  - Coombs positive giant cell hepatitis--a new feature of Evans' syndrome.

PMID- 9623418
TI  - Persistence of neurological damage induced by dietary vitamin B-12 deficiency.

PMID- 9623419
TI  - Abuse or metabolic disorder?

PMID- 9623420
TI  - A new college, a new direction in academic paediatrics?

PMID- 9623421
TI  - Weaning.

PMID- 9623422
TI  - Diaphragmatic dysfunction: an outmoded concept.

PMID- 9623423
TI  - Animal tissues into humans.

PMID- 9623424
TI  - Pulmonary function and pain after gastroplasty performed via laparotomy or
      laparoscopy in morbidly obese patients.
AB  - We have compared severely obese patients (body mass index > 35 kg m-2) undergoing
      laparoscopic or open gastroplasty (n = 15 in each group) to determine if
      laparoscopy results in any benefit in the obese. Postoperative pain, measured on
      a 100-mm visual analogue scale, and opioid consumption were recorded during the
      first two days after operation. Tests of pulmonary function were performed and
      SpO2 was measured 4 h after surgery and on days 1, 2 and 3 after operation. Pain
      at rest was similar in the two groups, but in the laparoscopy group, requirements
      for postoperative opioid were 50% less (P < 0.05). Pain intensity during
      mobilization and on coughing was significantly less after laparoscopy
      (differences between mean pain scores in both groups ranged from 20 to 32 mm
      during mobilization and from 32 to 34 mm during coughing). Forced vital capacity,
      forced expiratory volume in 1 s and peak expiratory flow rate were reduced
      significantly less after laparoscopic gastroplasty than after open gastroplasty
      (on day 1 forced vital capacity was reduced by 50% compared with 64%, forced
      expiratory volume in 1 s was reduced by 50% compared with 66% and peak expiratory
      flow rate by 45% compared with 60%). SpO2 values were significantly greater in
      the laparoscopy group (day 1: mean 95 (SD 2)% vs 91 (5)%; day 3: 97 (1)% vs 94
      (3)%). This study suggests that the beneficial effects observed after
      laparoscopic gastroplasty in morbidly obese patients were similar to those
      reported after laparoscopic cholecystectomy in non-obese patients.

PMID- 9623425
TI  - Extradural S(-)-bupivacaine: comparison with racemic RS-bupivacaine.
AB  - Bupivacaine has a chiral centre and is currently available as a racemic mixture
      of its two enantiomers: R(+)-bupivacaine and S(-)-bupivacaine. Preclinical
      studies have demonstrated that there is enantiomer selectivity of action with the
      bulk of central nervous system and cardiovascular toxicity residing with the R(+)
      isomer. The aim of this study was to compare the clinical efficacy and safety of
      S(-)-bupivacaine with racemic RS-bupivacaine for extradural anaesthesia. We
      studied 88 patients undergoing elective lower limb surgery under lumbar
      extradural anaesthesia who received 15 ml of 0.5% or 0.75% S(-)-bupivacaine, or
      0.5% RS-bupivacaine in a randomized, double-blind study. There was no difference
      in onset time, maximum spread of sensory block or intensity of motor block
      between the three groups. Duration of sensory block was significantly longer for
      0.75% S(-)-bupivacaine. We conclude that S(-)-bupivacaine has similar local
      anaesthetic characteristics to RS-bupivacaine when used for extradural
      anaesthesia.

PMID- 9623426
TI  - Addition of clonidine or fentanyl to local anaesthetics prolongs the duration of
      surgical analgesia after single shot caudal block in children.
AB  - Caudal anaesthesia is indicated for surgical procedures lasting less than 90 min.
      Fentanyl and clonidine are known to prolong postoperative caudal analgesia, but
      there are no data on their effect on duration of surgical analgesia. We evaluated
      if the addition of clonidine or fentanyl to local anaesthetics prolonged the
      duration of surgical analgesia after single shot caudal block in children in a
      randomized, double-blind study. We studied 64 children, aged 6-108 months,
      undergoing bilateral correction of vesicoureteral reflux which was expected to
      last more than 90 min. Patients were allocated to one of four groups: group O
      received 1 ml kg-1 of a mixture of 0.25% bupivacaine with epinephrine and 1%
      lidocaine in equal parts; group F received the same mixture of local anaesthetics
      in addition to fentanyl 1 microgram kg-1; group C received the same mixture of
      local anaesthetics in addition to clonidine 1.5 micrograms kg-1; and group C + F
      received the same mixture of local anaesthetics in addition to fentanyl 0.5
      microgram kg-1 and clonidine 0.75 microgram kg-1. Single shot caudal block was
      sufficient in only 57% of children in group O compared with 93% in groups C and F
      and 86% in group C + F (P = 0.035). Global assessment of anaesthesia, defined as
      the time from caudal injection to the first administration of analgesic (either
      during or after surgery), was significantly longer in the three groups of
      children who received additives compared with local anaesthetics alone (P =
      0.035), but there were no differences between the three additive groups. Vomiting
      was observed only in children who received fentanyl. Addition of clonidine or
      fentanyl to local anaesthetics prolonged the duration of surgical analgesia of
      caudal block, allowing single shot caudal anaesthesia to be recommended for
      surgery lasting 90-150 minutes. Clonidine had some advantages over fentanyl as it
      did not produce clinically significant side effects.

PMID- 9623427
TI  - Double-blind comparison of extradural block with three bupivacaine-ketamine
      mixtures in knee arthroplasty.
AB  - We have compared 0.5% bupivacaine 75 mg (group A; n = 15) with three 0.5%
      bupivacaine 75 mg-ketamine mixtures for extradural block in 59 ASA I-III patients
      undergoing total knee replacement in a randomized, double-blind study. The
      following doses of preservative-free 1% ketamine were used: 0.3 mg kg-1 (group B:
      n = 14); 0.5 mg kg-1 (group C: n = 5); and 0.67 mg kg-1 (group D: n = 15). Level
      of sensory block, degree of motor weakness and sedation scores were recorded
      before and after operation. Duration of postoperative analgesia was also noted.
      There was no difference between groups in median maximum level of sensory block
      (group A: T4 (range T10-T2); group B: T4 (T10-T2); group C: T4 (T8-T2); and group
      D: T3 (T8-C3)) or in the degree of motor block. Thirty-three of the 44 patients
      who received ketamine showed signs of systemic absorption (blurred vision,
      sedation) within 10 min of injection. There was no significant difference between
      groups in median duration of analgesia (group A: 240 (range 115-340) min; group
      B: 198 (97-460) min; group C: 150 (122-448) min; and group D: 210 (130-390) min).
      No patient suffered any adverse psychomimetic effects. We conclude that at the
      doses used, addition of ketamine to extradural bupivacaine did not improve
      extradural block in adult patients undergoing total knee replacement.

PMID- 9623428
TI  - Glycogen depletion and lactate accumulation in human intercostal muscles after
      administration of succinylcholine.
AB  - I.m. glycogen content, lactate concentration and staining intensity for glycogen
      in slow- (ST) and fast-twitch (FTa and FTb) fibres were determined in the
      external and internal intercostal muscles after thoracotomy. Thirteen patients
      received a precurarizing dose of a non-depolarizing neuromuscular blocking agent
      followed by the depolarizing agent, succinylcholine, to facilitate intubation of
      the trachea (succinylcholine group). Nine patients received pancuronium or
      gallamine (control group). There were no significant differences in ventilatory
      functional capacity between the two groups. In the external intercostal muscles,
      lower i.m. glycogen content was observed in the succinylcholine compared with the
      control group (P < 0.05). I.m. glycogen was depleted from the FT fibres and in
      particular from FTb fibres, while little depletion was noted in ST fibres. In
      both the external and internal intercostal muscles, a higher lactate
      concentration was observed in the succinylcholine than in the control group (P <
      0.05). The results indicate that the use of succinylcholine for tracheal
      intubation stimulated breakdown of i.m. glycogen, particularly in fast-twitch
      muscle fibres, and caused accumulation of lactate in intercostal muscles.

PMID- 9623429
TI  - Augmentation of the neuromuscular blocking effects of cisatracurium during
      desflurane, sevoflurane, isoflurane or total i.v. anaesthesia.
AB  - We have evaluated the enhancement of cisatracurium-induced neuromuscular block by
      potent inhalation anaesthetic agents, by constructing dose-effect curves for
      cisatracurium in 84 patients during anaesthesia with 1.5 MAC (70% nitrous oxide)
      desflurane, sevoflurane, isoflurane or total i.v. anaesthesia (TIVA).
      Acceleromyography (TOF-Guard) and train-of-four (TOF) stimulation of the ulnar
      nerve were used (2 Hz every 12 s). Cisatracurium was administered in increments
      of 15 micrograms kg-1 until depression of T1/T0 > 95% was reached. ANOVA was used
      for statistical analysis (alpha = 0.05, beta = 0.2). Depression of T1/T0 during
      potent inhalation anaesthesia was enhanced compared with TIVA. ED50 and ED95
      values of cisatracurium were 15 (SD 5) and 34 (10) micrograms kg-1 for
      desflurane; 15 (4) and 32 (7) micrograms kg-1 for sevoflurane; and 15 (5) and 33
      (9) micrograms kg-1 for isoflurane. These were significantly lower than the
      values for TIVA (21 (4) and 51 (13) micrograms kg-1) (P < 0.01 in each case).
      After equi-effective dosing, times to T1/T0 = 25% were similar in all groups (19
      (7), 19 (5), 20 (5) vs 16 (4) min). Recovery index25-75% and time to a TOF ration
      of 0.70 were prolonged significantly by desflurane and sevoflurane compared with
      TIVA (18 (5), 19 (8) vs 12 (4) min and 43 (11), 44 (10) vs 35 (5) min,
      respectively), whereas the difference was not significant for isoflurane (14 (6)
      and 41 (7) min).

PMID- 9623430
TI  - Effects of hypothermia on thrombelastography in patients undergoing
      cardiopulmonary bypass.
AB  - Thrombelastography (TEG) correlates with postoperative chest drain output in
      patients undergoing cardiopulmonary bypass (CPB). In vitro incubation with
      heparinase allows TEG monitoring during CPB, despite heparin anticoagulation.
      Hypothermia impairs coagulation, but these effects cannot be assessed by standard
      coagulation tests performed at 37 degrees C. The aim of this study was to assess
      the effects of hypothermia on TEG. Therefore, we have compared normothermic and
      temperature-adapted TEG in 30 patients undergoing CPB. Our data showed
      significantly impaired reaction time (r), kinetic time (k), and angle alpha
      (alpha) in temperature-adapted compared with normothermic TEG. Maximum amplitude
      (MA), reflecting absolute clot strength, was not affected at temperatures of 33
      37 degrees C. These findings indicate a decrease in the speed of clot formation,
      but not absolute deterioration in clot quality. Furthermore, heparinase-modified
      TEG indicated that there were nine cases in which heparin effects persisted after
      heparin reversal with protamine, providing a rational guide to protamine therapy.

PMID- 9623431
TI  - Benefits of intraoperative skin surface warming in cardiac surgical patients.
AB  - We have investigated patients undergoing cardiac surgery with hypothermic bypass
      to see if the addition of skin surface warming during systemic rewarming on
      bypass (heated group, n = 43) would improve perioperative thermal balance
      compared with conventional management without skin warming (control group, n =
      43) in an open, randomized, controlled study. Intraoperative skin warming with a
      water mattress and forced warm air over the face, neck and shoulders attenuated
      the afterdrop in nasopharyngeal temperature after weaning from bypass (2.3 (1.2)
      degrees C and 1.3 (0.5) degrees C in the control and heated groups, respectively)
      (P < 0.05) and resulted in higher rectal temperature 4 h after surgery. Despite
      similar standard coagulation tests, heated patients had lower blood loss via the
      chest tubes (600 (264) ml vs 956 (448) ml in control patients) (P < 0.05) and
      less requirements for i.v. colloid infusion (1662 (404) ml vs 1994 (389) ml) (P <
      0.05). There was a significant inverse correlation between rectal temperature on
      arrival in the ICU and postoperative blood loss (r = 0.57, P < 0.001). These data
      suggest that additional skin surface warming with a water mattress and forced
      warm air helped to preserve perioperative thermal balance and may contribute to
      reduced bleeding after cardiac surgery.

PMID- 9623432
TI  - Pharmacokinetics of propofol during conscious sedation using target-controlled
      infusion in anxious patients undergoing dental treatment.
AB  - Infusion of propofol by a target-controlled infusion (TCI) system is effective in
      achieving conscious sedation for anxious patients presenting for dental surgery.
      It is a common clinical observation that anxious patients require more
      anaesthetic drugs than non-anxious individuals. In study 1 we have defined blood
      propofol concentrations necessary for conscious sedation in both anxious (n = 23)
      and non-anxious (n = 18) patients. The pump performance of the TCI system, using
      Gepts' pharmacokinetic model, was evaluated in these two patient groups.
      Subsequently, clearance of propofol was compared in the two groups. Mean measured
      venous serum propofol concentrations obtained between 20 and 35 min after the
      optimal sedation level was reached were 1.6 (SD 0.2) micrograms ml-1 in the
      anxious patients compared with 1.7 (0.3) micrograms ml-1 in the control group
      (study 1) and 1.4 (0.27) micrograms ml-1 in study 2. The pump systematically
      overpredicted measured propofol concentrations in both groups (study 1). There
      was no significant difference in propofol clearance between the two groups. In
      study 2, an optimized set of microconstants was derived which should more
      accurately predict the pharmacokinetic profile of the anxious population and this
      set was tested prospectively in another group of 12 anxious dental patients. Bias
      and precision with the optimized kinetic set were significantly less than the
      values obtained in study 1. We conclude that there was no significant
      pharmacokinetic differences between anxious and non-anxious subjects receiving
      subanaesthetic doses of propofol for conscious sedation.

PMID- 9623433
TI  - Positive pressure ventilation with the laryngeal mask airway in non-paralysed
      patients: comparison of sevoflurane and propofol maintenance techniques.
AB  - We have compared anaesthetic maintenance and emergence characteristics of
      propofol and sevoflurane with the laryngeal mask airway (LMA) at commonly used
      doses in 185 ASA I-II patients, in a randomized, prospective study. Anaesthesia
      was induced with propofol 2.5-3.5 mg kg-1 and fentanyl 1-3 micrograms kg-1.
      Neuromuscular blocking agents were not used. All patients underwent positive
      pressure ventilation (PPV) with tidal volumes of 6-8 ml kg-1 to maintain normal
      end-tidal carbon dioxide concentration. Anaesthesia was maintained with 66%
      nitrous oxide in oxygen and infusion of propofol 6 or 8 mg kg-1 h-1, or 1% or
      1.5% end-tidal sevoflurane. There were no failed insertion attempts and adequate
      ventilation was achieved in all patients. During emergence, there was a greater
      incidence of excitatory phenomena with 1% and 1.5% sevoflurane (95% confidence
      intervals (CI) 4-19%) compared with propofol (95% CI 0-4%). Sevoflurane 1.0% (95%
      CI 37-71%) was associated with the greatest overall incidence of respiratory and
      haemodynamic problems. This was significantly higher compared with propofol 6 mg
      kg-1 h-1 (95% CI 19-36%). Shorter times to LMA removal were observed with 1% and
      1.5% sevoflurane compared with propofol (P < 0.0002). Postoperative problems did
      not differ between groups. We conclude that propofol 6-8 mg kg-1 h-1 and 1.5%
      sevoflurane were suitable for maintenance of anaesthesia for musculoskeletal
      surgery in non-paralysed ASA I-II patients undergoing PPV with the LMA. Emergence
      was more rapid with sevoflurane, but was associated with more excitatory
      phenomena.

PMID- 9623434
TI  - Catheter deadspace: a source of error during tonometry.
AB  - Tonometry of PCO2 is a promising method for assessing the oxygen supply to demand
      ratio of the gastrointestinal mucosa in critically ill patients. A balloon-tipped
      tonometer is introduced into the stomach or sigmoid colon, and saline is
      instilled into the balloon. After a time to allow partial equilibration with
      intraluminal PCO2, saline is aspirated and PCO2 is measured. Intermittent
      instillation and aspiration of saline allows serial PCO2 measurements, provided
      correction factors are used to calculate the PCO2 value expected at full
      equilibration from the PCO2 values measured after short dwell times. The
      technique is not yet widely applied, partly because of methodological
      controversies. We evaluated the role of the catheter deadspace as a source of
      error during PCO2 tonometry. The increase in PCO2 in sigmoid-type tonometers with
      a normal length (normal tonometer (NT)) and in those with a 50% increase in
      length and thus deadspace (extended tonometer (ET)), in a saline bath at a PCO2
      of 4.8 kPa was assessed. Saline dwell times were 10, 20, 30, 45, 60 and 90 min
      and the time-dependent PCO2 increase was determined at deadspace PCO2 values of
      approximately 4.0 and 8.0 kPa following contamination of the catheter deadspace
      after immersion in saline baths at PCO2 values of 4.8 and 9.6 kPa, respectively,
      before each measurement cycle. In another experiment, the tonometer was rinsed
      between measurement cycles to remove deadspace saline containing carbon dioxide
      and to obviate contamination of instilled saline. PCO2 was measured in a blood
      gas analyser, taking into account measurement bias in saline. Failure to remove
      deadspace saline between measurement cycles resulted in an overestimation of 10%
      and 6% for the NT and 16% and 10% for the ET, at saline dwell times of 10 and 20
      min, respectively, at a deadspace PCO2 of approximately 4.0 kPa. At a deadspace
      PCO2 of approximately 8.0 kPa, PCO2 was overestimated by 17%, 11% and 5% for the
      NT and 31%, 20% and 11% for the ET, at dwell times of 10, 20 and 30 min,
      respectively. Rinsing the NT/ET resulted in accurate assessment of PCO2 at all
      dwell times, but the dwell time-dependent increase in PCO2 was slightly slower in
      the ET, particularly at 10 min, after a sink effect of the increased deadspace.
      Hence, a previously unrecognized deadspace effect caused error during PCO2
      tonometry, particularly with short dwell times. This potentially large error can
      be avoided by rinsing the tonometer before each measurement cycle, allowing
      accurate PCO2 tonometry even at 10-min saline dwell times, provided that
      correction factors are used that are specific for catheter size. These findings
      may help to widen the clinical applicability of tonometry.

PMID- 9623435
TI  - Bispectral index: comparison of two montages.
AB  - We have compared fronto-central and bifrontal montages using a new EEG monitor,
      the Aspect A-1000. The monitor uses bispectral analysis to derive an index of
      anaesthetic depth, the bispectral index (BIS). We compared reliability, impedance
      and BIS for each montage. ECG electrodes placed in a bifrontal montage were more
      reliable than silver dome electrodes in a fronto-central montage and both types
      of electrodes had impedances in the clinically useful range. However, BIS values
      derived from each montage were found to differ in an unpredictable manner. The
      bifrontal montage is easy to apply and reliable but it is not comparable with a
      fronto-central montage. We conclude that the BIS may be useful for following
      trends in anaesthetic depth in individual cases but it is less helpful when
      making comparison between patients or as a single value.

PMID- 9623436
TI  - Laryngoscopy and fibreoptic intubation in acromegalic patients.
AB  - Acromegaly is recognized as a cause of difficulty in airway management and
      tracheal intubation. We evaluated prospectively the conditions for laryngoscopy
      and fibreoptic intubation in 15 acromegalic patients. Each patient served as his
      or her own control. Ventilation of the lungs with a face mask was successful in
      all patients. In five of 15 patients the vocal cords could not be seen using the
      Macintosh laryngoscope with a size 5 blade. Difficult laryngoscopy was associated
      significantly with the number of attempts required to see the vocal cords with
      the fibrescope (P < 0.01, Spearman rank correlation). The larynx could not be
      seen with both techniques in one patient, and the trachea was intubated blindly
      with the help of an introducer. Our results showed that fibreoptic intubation may
      prove difficult or fail in acromegalic patients. Difficulties in seeing the vocal
      cords with a fibrescope were present most often in patients who also had probable
      intubation difficulties with a rigid laryngoscope.

PMID- 9623437
TI  - Effect of continuous spinal remifentanil infusion on behaviour and spinal
      glutamate release evoked by subcutaneous formalin in the rat.
AB  - Injection of formalin into the hind paw of the rat evokes a biphasic nociceptive
      behavioural response, which is considered to be an animal model of postoperative
      pain in humans. The initial response (phase 1) is caused by activation of
      peripheral nociceptors and is followed by a second phase attributed to ongoing
      activity in primary afferents and increased sensitivity of dorsal horn neurones.
      The latter effect is thought to result from glutamate-mediated N-methyl-D
      aspartate receptor activation. In studies to date it has been difficult to
      discriminate mechanisms underlying phase 1 and phase 2 events because of the long
      lasting half-times of intrathecally administered opioids. To further
      understanding of the opioid pharmacology of the two different phases of the
      formalin test, we have studied behavioural activity and spinal glutamate release
      after intrathecal administration of remifentanil, a new short-lasting mu opioid.
      Intrathecal remifentanil 3 micrograms microliter-1 min-1 delivered during phase 1
      inhibited behavioural response during phase 1 (100%), but did not abolish
      subsequent phase 2 behavioural activity completely (67 (12) %). Intrathecal
      remifentanil administered separately in phase 1 and phase 2 revealed a similar
      ED50 (0.2 microgram microliter-1 min-1) for inhibition of the behavioural
      responses. In vivo, spinal microdialysis showed incomplete reduction in glutamate
      concentrations in response to intrathecal remifentanil administration; this in
      turn inhibited phase 1 behavioural responses. Therefore we contend that
      supramaximal doses of intrathecal remifentanil sufficient to inhibit phase 1
      activity still permitted sufficient glutamate release to allow spinal
      facilitation. Incomplete suppression of spinal excitatory neurotransmitter
      release by intrathecal opioids is consistent with spinal wind-up that is
      triggered during phase 1 and results in phase 2 afferent drive. This might
      reflect one of the mechanisms underlying post-operative pain.

PMID- 9623438
TI  - Changes in right atrial catecholamine content in naive rats and after naloxone
      induced withdrawal.
AB  - In this study, we determined if changes in heart catecholamine content during
      naloxone-induced withdrawal correlated with modifications in heart rate. In
      addition, we determined plasma concentrations of corticosterone as an index of
      the hypothalamo-pituitary-adrenal (HPA) axis. The effects of naloxone on
      norepinephrine, epinephrine or dopamine content and turnover, plasma
      concentrations of corticosterone and the mechanical response of the right atria
      of the rat were studied. Male rats were implanted with placebo or morphine
      pellets for 7 days. On the day of sacrifice, animals were injected with saline or
      naloxone 1 mg kg-1 s.c. to precipitate a withdrawal syndrome. Administration of
      naloxone to morphine-treated (tolerant) animals induced a decrease in atrial
      content of norepinephrine, epinephrine and dopamine (290.2 (11.9) ng g-1, 15.6
      (2.1) ng g-1 and 9.52 (0.5) ng g-1, respectively) and an increase (1.38 (0.2) ng
      g-1 in the dihydroxy phenyl acetic acid/dopamine (DOPAC/DA) ratio. Administration
      of naloxone to morphine-treated animals enhanced plasma concentrations of
      corticosterone (435.8 (27.6) ng ml-1). In the isolated right atria, L-naloxone
      induced an increase in atrial rate in preparations from morphine-treated rats
      whereas in placebo-pelleted (naive) rats, L-naloxone induced a decrease. In
      contrast, administration of D-naloxone (inactive isomer) produced a decrease in
      atrial rate in preparations from placebo or morphine-treated rats. We conclude
      that this study has provided evidence that naloxone-induced withdrawal was
      characterized by activation of catecholaminergic neurones in the heart that was
      accompanied by an increase in atrial rate.

PMID- 9623439
TI  - Surfactant impairment after mechanical ventilation with large alveolar surface
      area changes and effects of positive end-expiratory pressure.
AB  - We have assessed the effects of overinflation on surfactant function and
      composition in rats undergoing ventilation for 20 min with 100% oxygen at a peak
      inspiratory pressure of 45 cm H2O, with or without PEEP 10 cm H2O (groups 45/10
      and 45/0, respectively). Mean tidal volumes were 48.4 (SEM 0.3) ml kg-1 in group
      45/0 and 18.3 (0.1) ml kg-1 in group 45/10. Arterial oxygenation in group 45/0
      was reduced after 20 min compared with group 45/10 (305 (71) vs 564 (10) mm Hg);
      maximal compliance of the P-V curve was decreased (2.09 (0.13) vs 4.16 (0.35) ml
      cm H2O-1 kg-1); total lung volume at a transpulmonary pressure of 5 cm H2O was
      reduced (6.5 (1.0) vs 18.8 (1.4) ml kg-1) and the Gruenwald index was less (0.22
      (0.02) vs 0.40 (0.05)). Bronchoalveolar lavage fluid from the group of animals
      who underwent ventilation without PEEP had a greater protein concentration (2.18
      (0.11) vs 0.76 (0.22) mg ml-1) and a greater minimal surface tension (37.2 (6.3)
      vs 24.5 (2.8) mN m-1) than in those who underwent ventilation with PEEP. Group
      45/0 had an increase in non-active to active total phosphorus compared with
      nonventilated controls (0.90 (0.16) vs 0.30 (0.07)). We conclude that ventilation
      in healthy rats with peak inspiratory pressures of 45 cm H2O without PEEP for 20
      min caused severe impairment of pulmonary surfactant composition and function
      which can be prevented by the use of PEEP 10 cm H2O.

PMID- 9623440
TI  - Effects of inhalation anaesthetics on the release of acetylcholine in the rat
      cerebral cortex in vivo.
AB  - By analysing the EEG, reticular multi-unit activity and behavioural changes, we
      have classified general anaesthetics into three groups: central nervous system
      (CNS) depressant, CNS excitant and epileptogenic agents. Changes in CNS neural
      activity are associated with alteration in transmitter release. We have attempted
      to clarify the actions of widely used inhalation anaesthetics, such as isoflurane
      (CNS depressant), nitrous oxide (CNS excitant) and sevoflurane (epileptogenic) on
      acetylcholine (ACh) release in the cerebral cortex using brain microdialysis. ACh
      release was suppressed by isoflurane and sevoflurane in a dose-related manner but
      recovered on wash-out. There were no significant differences between the effects
      of sevoflurane and isoflurane at the same MAC values. In contrast, ACh release
      was enhanced significantly by nitrous oxide. These findings indicate that the
      response of the cortical cholinergic cells to different anaesthetics reflects
      their neurophysiological characteristics, that is whether they stimulate or
      suppress CNS neurones.

PMID- 9623441
TI  - Myocardial stunning in the neonate.

PMID- 9623442
TI  - Neuromuscular monitoring by intensive care nurses: comparison of
      acceleromyography and tactile assessment.
AB  - We have compared tactile assessment of the train-of-four (TOF) count and TOF
      ratio by nursing staff, with measurements made by a new acceleromyographic
      monitor, the TOF-Watch. We assessed neuromuscular block in 30 sedated intensive
      care patients receiving a continuous infusion of atracurium. Five nurses made a
      tactile assessment of neuromuscular block in each patient within a 5-min period.
      Each assessment was paired with a blinded TOF-Watch measurement. The nurses were
      accurate in assessing twitch count in 55% of measurements and they tended to
      overestimate the degree of block using tactile assessment of TOF ratio.

PMID- 9623443
TI  - Accelerated recovery and disposition from rocuronium in an end-stage renal
      failure patient on chronic anticonvulsant therapy with sodium valproate and
      primidone.
AB  - An end-stage renal failure patient, receiving chronic treatment with the
      anticonvulsants, sodium valproate and primidone, showed accelerated recovery with
      enhanced elimination (T1/2(z) = 52 min) and clearance (Cl = 14.4 ml min-1 kg-1)
      of rocuronium. The pharmacokinetic and pharmacodynamic effects of rocuronium in
      this patient are compared with those published for healthy and renal failure
      patients. Increased hepatic binding of rocuronium rather than metabolism is
      suggested as the possible cause of this effect.

PMID- 9623444
TI  - Multicentre evaluation of ryanodine contracture testing in malignant
      hyperthermia. The European Malignant Hyperthermia Group.
AB  - A common protocol for in vitro contracture testing using the plant alkaloid
      ryanodine has been used by the European Malignant Hyperthermia Group since 1993.
      This protocol describes a test using I mumol/litre of high purity ryanodine (98%)
      added as a single bolus dose. The main aim of this study was to compare the
      results obtained with this test between laboratories with a view to assessing the
      validity of adopting common diagnostic end-points for use in future collaborative
      studies. In order to do this it was first necessary to determine the optimum cut
      off values of the end-points for discriminating between patients diagnosed as
      susceptible or not to malignant hyperthermia. The end-points under evaluation
      were expressed in terms of time after application of ryanodine at which a certain
      degree of contracture develops. In this study, four end-points were investigated:
      time to initial contracture development (Ot); time to development of a 10-mN
      contracture (10t); time from addition of ryanodine to when baseline tension
      exceeds pre-drug tension (0tp); and time for contracture to reach 10 mN above pre
      drug baseline tension (10tp). This protocol was developed initially and used by
      three investigating centres and the initial assessment of the end-points and
      their discriminatory ability was made using the first 100 patients from each of
      centres 1 and 2, and the first 90 patients from centre No. 3. Optimal cut-off
      values for each of the end-points were determined using logistic regression
      analysis. Discriminatory ability was improved by combining the Ot and 10t end
      points (P < 0.05) but not significantly by combining the 0tp and 10tp end-points.
      Both methods of categorization were highly sensitive and specific compared with
      the current standard diagnostic tests. Results from eight additional diagnostic
      centres which have used the ryanodine contracture test more recently, while
      indicating that susceptible and normal individuals can be distinguished within a
      single laboratory, produced a level of variability between testing centres for
      the ryanodine contracture test that is incompatible with the use of common cut
      off values. Possible causes for this variability between laboratories are
      discussed.

PMID- 9623445
TI  - The human cardiovascular response to fluothane anaesthesia. 1956.

PMID- 9623446
TI  - Anaesthesia after exhaustive exercise.

PMID- 9623447
TI  - Pain after laparoscopic cholecystectomy.

PMID- 9623448
TI  - Ondansetron compared with metoclopramide in the treatment of PONV.

PMID- 9623449
TI  - Sevoflurane for difficult intubation in children.

PMID- 9623450
TI  - Caudal tramadol for postoperative analgesia in hypospadias surgery.

PMID- 9623451
TI  - Bair Hugger active patient warming system.

PMID- 9623452
TI  - Inappropriate use of placebo.

PMID- 9623453
TI  - Bradycardia during rapid inhalation induction with sevoflurane in children.

PMID- 9623454
TI  - Effect of temperature on diaphragmatic function.

PMID- 9623455
TI  - Operative cholangiography: the debate continues.

PMID- 9623456
TI  - Single- versus multiple-dose antimicrobial prophylaxis for major surgery: a
      systematic review.
AB  - BACKGROUND: Single-dose antimicrobial prophylaxis for major surgery is a widely
      accepted principle; recommendations have been based on laboratory studies and
      numerous clinical trials published in the last 25 years. In practice, single-dose
      prophylaxis has not been universally accepted and multiple-dose regimens are
      still used in some centres. Moreover, the principle has recently been challenged
      by the results of an Australian study of vascular surgery. The aim of this
      current systematic review is to determine the overall efficacy of single versus
      multiple-dose antimicrobial prophylaxis for major surgery and across surgical
      disciplines. METHODS: Relevant studies were identified in the medical literature
      using the MEDLINE database and other search strategies. Trials included in the
      review were prospective and randomized, had the same antimicrobial in each
      treatment arm and were published in English. Rates of postoperative surgical site
      infections (SSI) were extracted, 2 x 2 tables prepared and odds ratios (OR) [with
      95% confidence intervals (95% CI)] calculated. Data were then combined using
      fixed and random effects models to provide an overall figure. In this context, a
      high value for the combined OR, with 95% CI > 1.0, indicates superiority of
      multiple-dose regimens and a low OR, with 95% CI < 1.0, suggests the opposite. A
      combined OR close to 1.0, with narrow 95% CI straddling 1.0, indicates no clear
      advantage of one regimen over another. Further subgroup analyses were also
      performed. RESULTS: Combined OR by both fixed (1.06, 95% CI, 0.89-1.25) and
      random effects (1.04, 95% CI, 0.86-1.25) models indicated no clear advantage of
      either single or multiple-dose regimens in preventing SSI. Likewise, subgroup
      analysis showed no statistically significant differences associated with type of
      antimicrobial used (beta-lactam vs other), blinded wound assessment, length of
      the multiple-dose arm (> 24 h vs 24 h or less) or type of surgery (obstetric and
      gynaecological vs other). CONCLUSIONS: Continued use of single-dose antimicrobial
      prophylaxis for major surgery is recommended. Further studies are required,
      especially in previously neglected surgical disciplines.

PMID- 9623457
TI  - The Quality of Surgical Care Project: a model to evaluate surgical outcomes in
      Western Australia using population-based record linkage.
AB  - BACKGROUND: The aim of this study is to establish a model to evaluate surgical
      outcomes and, where indicated, recommend changes to improve the quality of
      surgical care in Western Australia (WA). Open resection for aneurysm of the
      abdominal aorta was the first procedure evaluated and the results are reported in
      an accompanying paper. METHODS: The Quality of Surgical Care Project (QSCP) is
      conducted under the aegis of the Royal Australasian College of Surgeons (RACS) in
      WA, and brings together a multidisciplinary team of surgeons, public health
      researchers and health service administrators. The Western Australia Health
      Services Research Linked Database (the WA Linked Database) is used to provide
      linked chains of patients records residing in the state health department from
      the following sources: hospital morbidity data system, birth and death records,
      mental health services data, cancer registrations and midwives' notifications.
      This links 16 years of population-based patient records from 1980, including all
      public and private hospital admissions and re-admissions. The Quality of Surgical
      Care Project was established to use and to correlate the data from the WA Linked
      Database. RESULTS: The result is a powerful database for a contained population
      that is available for scientific analysis by a multidisciplinary team of clinical
      epidemiologists, surgeons and health service managers. Users will have the
      ability to establish benchmark standards for the outcomes of surgical procedures
      in WA for use in quality improvement programmes run by the College and will
      facilitate self-directed performance auditing activities as a commitment to
      greater community accountability. CONCLUSIONS: The Quality of Surgical Care
      Project provides a potential model of benefits to be realized by both the medical
      profession and the community through multidisciplinary collaboration supported by
      adequate information. Although migration from WA is relatively low, future
      linkage to the state electoral roll will allow correction for any population
      change.

PMID- 9623458
TI  - The Quality of Surgical Care Project: benchmark standards of open resection for
      abdominal aortic aneurysm in Western Australia.
AB  - BACKGROUND: The Quality of Surgical Care Project (QSCP) was established in May
      1996, to evaluate surgical outcomes and where indicated, recommend changes to
      improve the quality of surgical care in Western Australia (WA). The purpose of
      this study is to establish benchmark standards in WA for operative mortality, 5
      year survival and length of stay in all patients who were surgically treated for
      aneurysm of the abdominal aorta (AAA) in WA. METHODS: The WA Linked Database was
      used to link the morbidity and mortality records of all patients admitted and
      surgically treated for AAA in WA from 1985 to 1994. The linked chains of de
      identified hospital morbidity and death records were selected using diagnostic
      and procedure codes pertaining to AAA. Three groups were separated for analysis:
      those admitted for rupture, those admitted for elective repair, and those who
      were admitted to hospital as an emergency without mention of rupture but who
      underwent repair for AAA. Independent analysis for gender and patients 80 years
      or more were included in the study. Patients were excluded from the study if they
      were less than 55 years of age. RESULTS: A total of 1475 cases (1257 males, 218
      females) were identified. The mean age in elective cases was 70.4 years in males
      and 72.4 years in females, and for rupture the mean ages were 71.9 and 74.8
      years, respectively. Median length of stay for males was 12 days for elective
      cases. Admission type or age did not significantly influence length of stay.
      Thirty-day mortality in males was 4.4% for elective repair and 36.7% for ruptured
      AAA and 5-year survival was 71.7 and 47.7%, respectively. The overall case
      fatality rate for ruptured AAA was 79.3% which included those cases who died from
      rupture without being admitted to hospital. CONCLUSIONS: These community-wide
      data provide a realistic measure of surgical performance for open repair of AAA.
      The outcomes for elective and rupture repair for AAA compare favourably with
      standards reported by international centres of excellence. They also support the
      use of this procedure in patients over 80 years of age with rupture. This
      information can be used for ongoing audit purposes and as a benchmark for the
      introduction of new treatment modalities.

PMID- 9623459
TI  - Breast cancer outcomes at the Strathfield Breast Centre.
AB  - BACKGROUND: Breast cancer is the most commonly diagnosed cancer and the most
      common cause of cancer death in women. This report presents outcomes from a
      multidisciplinary breast clinic established in 1989 with the specific aim of
      providing a rapid, integrated assessment service for patients with breast
      disease. METHODS: A prospective data collection and analysis using a Microsoft
      Access (Microsoft Corp., North Ryde, NSW, Australia) database was established and
      has collected information on all patients presenting for diagnosis or ongoing
      management of breast cancer. Data on survival were obtained by routine follow-up
      visits or contact with the patient's general practitioner. RESULTS: Patient age,
      mode of presentation and histopathology were similar to other population-based
      studies in Australia. Ninety-three per cent of the patients had a diagnosis
      confirmed on the day of consultation. The average time between diagnosis and
      surgery was 11.9 days. Breast preserving surgery was attempted in 68% and
      achieved in 50% of cases, 67% of patients had one stage surgery. Five-year
      disease-free survival was 74% and is comparable with other reports. CONCLUSIONS:
      The centralization of services and expertise has enabled us to provide efficient
      service and achieve internationally comparable outcomes.

PMID- 9623460
TI  - Diagnosis of small sized invasive breast cancer by an Australian mammography
      screening service: surrogate end-points for mortality reduction.
AB  - BACKGROUND: The percentage of screen-detected infiltrating cancers that are
      small, the percentage that are node-negative and the percentage of those that are
      grade 3 and small, are surrogate end-points for the main object of breast
      screening, namely the reduction in mortality from breast cancer in the screened
      population. METHODS: This study reports these end-points; that is, the prognostic
      features of invasive cancers, as detected by the Central and Eastern Sydney
      Service of BreastScreen NSW. The data reported were collected by the Service on
      women who attended for screening between March 1988 and December 1994. RESULTS:
      Breast cancer detection rates for women aged 50-69 years were 78 per 10,000 for
      prevalent screens and 37 per 10,000 for incident screens with 36 and 37%,
      respectively, of the invasive cancers being < or = 10 mm in size and 64 and 70%,
      respectively, being < or = 15 mm in size. Seventeen per cent of invasive cancers
      were grade 3 and of these 45% were < or = 15 mm in size. Axillary nodal
      dissection was carried out in 86% of invasive cancers and 69% of these were node
      negative, the rates of node negativity being higher for small-sized cancers.
      CONCLUSIONS: Breast cancer detection rates, small invasive cancer detection
      rates, the percentage of small grade 3 cancers and the node negativity rates
      indicate that the potential long-term mortality benefits of mammography screening
      should be achieved. These rates could be used to underpin a review of the
      Australian Accreditation Standards.

PMID- 9623461
TI  - Newly arising fibroadenomas in women aged 35 and over.
AB  - BACKGROUND: Fifty-one cases of de novo fibroadenoma in women aged 35 years and
      older were found during an analysis of 117,729 visits to the Wesley Breast Clinic
      from 1990 to 1996. METHODS: The clinical, mammographic and ultrasound diagnosis
      of fibroadenoma was confirmed by either fine needle aspiration cytology or
      histology of an open biopsy specimen. In all cases there was a well-documented
      previous visit available for review, at which there was no clinical or
      radiological evidence of the fibroadenoma. RESULTS: Thirty-seven of the de novo
      fibroadenomas were palpable, the remainder satisfying strict mammographic and/or
      ultrasound criteria. Four of the new fibroadenomas were in women aged 50-52.
      CONCLUSIONS: This study provides information about the natural history of
      fibroadenomas, confirming that they can appear for the first time in middle-aged
      women. This has important clinical implications, since new lesions appearing in
      women over 35 have tended to be automatically categorized as suspicious of
      carcinoma. However, a multidisciplinary approach involving clinical examination,
      mammography, ultrasound, and fine needle aspiration cytology or core biopsy can
      result in a confident diagnosis of fibroadenoma. This will allow some women with
      new lesions to be managed conservatively rather than by open biopsy.

PMID- 9623462
TI  - Non-operative treatment of breast abscesses.
AB  - BACKGROUND: Breast abscesses are conventionally treated by incision and drainage.
      This often requires general anaesthesia and a hospital stay. Non-operative
      treatment by needle aspiration and oral antibiotics is reported as a viable
      alternative. METHODS: All patients who presented with breast abscesses and who
      were assessed by one surgeon between November 1995 and January 1997 were managed
      using a conservative approach and they are the subjects of this study. RESULTS:
      Twenty-one consecutive patients were seen over a period of 26 months. All had non
      lactational breast abscesses. Nineteen patients were successfully treated by
      needle aspiration and antibiotics while two patients required incision and
      drainage. The mean size of the aspirated abscesses was 3.5 cm (range 1-15 cm) and
      required an average of 2.4 aspirations (range 1-5). Of those treated by
      aspiration, three patients developed recurrent abscesses, two of which were
      successfully managed by repeat aspiration while one patient eventually required
      surgery. CONCLUSIONS: The majority of non-lactational breast abscesses seen in
      clinical practice can be treated without surgery by a combination of needle
      aspiration and antibiotics.

PMID- 9623463
TI  - Routine cholecystocholangiography: a viable alternative during laparoscopic
      cholecystectomy.
AB  - BACKGROUND: The advantages of cholangiography during laparoscopic cholecystectomy
      (LC), including identification of biliary anatomy and biliary calculi, are well
      known. The usefulness of cholecystocholangiography (CCC), by direct injection
      through the gall-bladder, compared to the more popular cystic duct
      cholangiography (CDC), however, is not so well known. METHODS: Two hundred
      consecutive patients who underwent LC were included in a prospective study of
      routine CCC. Between 5 and 60 mL of contrast is injected through the gall-bladder
      fundus, using image intensifier control. RESULTS: Cholecystocholangiography was
      attempted in 194 cases and was successful in 157 (80.9%). Twenty-one of the 37
      cases with a failed CCC proceeded to have a successful CDC, giving an overall
      cholangiography success rate of 91.8%. The presence of acute inflammation
      decreased the success rate. Eleven (6%) true positive cases of common bile duct
      (CBD) calculi were demonstrated (nine on CCC and two on CDC after failed CCC).
      There was one case of false positive CBD calculus and no false negatives.
      CONCLUSIONS: We have found that the routine use of CCC during LC is safe,
      successful, quick to perform, and does not prevent conversion to attempted CDC in
      the cases where it fails. Cholecystocholangiography may have advantages over CDC
      and be an alternative as the preferred imaging technique.

PMID- 9623464
TI  - Computers in medical education 2. Use of a computer package to supplement the
      clinical experience in a surgical clerkship: an objective evaluation.
AB  - BACKGROUND: Student teaching of surgery has been devolved from the university in
      an effort to increase and broaden undergraduate clinical experience. In order to
      ensure uniformity of learning we have defined learning objectives and provided a
      computer-based package to supplement clinical teaching. A study was undertaken to
      evaluate the place of computer-based learning in a clinical environment. METHODS:
      Twelve modules were provided for study during a 6-week attachment. These covered
      clinical problems related to cardiology, neurosurgery and gastrointestinal
      haemorrhage. Eighty-four fourth-year students undertook a pre- and post-test
      assessment on these three topics as well as acute abdominal pain. No extra
      learning material on the latter topic was provided during the attachment.
      RESULTS: While all students showed significant improvement in performance in the
      post-test assessment, those who had access to the computer material performed
      significantly better than did the controls. Within the topics, students in both
      groups performed equally well on the post-test assessment of acute abdominal pain
      but the control group's performance was significantly lacking on the topic of
      gastrointestinal haemorrhage, suggesting that the bulk of learning on this
      subject came from the computer material and little from the clinical attachment.
      CONCLUSIONS: This type of learning resource can be used to supplement the
      student's clinical experience and at the same time monitor what they learn during
      clinical clerkships and identify areas of weakness.

PMID- 9623465
TI  - Military surgery in Rwanda: comment.

PMID- 9623466
TI  - Military surgery in Rwanda: comment.

PMID- 9623467
TI  - Adductor myonecrosis following prostate biopsy: comment.

PMID- 9623468
TI  - A simple index to predict prognosis independent of axillary node information in
      breast cancer: comment.

PMID- 9623469
TI  - Octreotide scintigraphy: a prerequisite for liver transplantation for metastatic
      gastrinoma.

PMID- 9623470
TI  - Three-dimensional ultrasonography of normal fetal heart: comparison with two
      dimensional imaging.
AB  - Thirty-one high-risk patients (16 to 35 weeks' gestation) underwent two
      dimensional and three-dimensional ultrasonography to compare two-dimensional and
      non-cardiac-gated three-dimensional ultrasonography of the normal fetal heart.
      After normal two-dimensional studies, three-dimensional sonographic volumes were
      acquired without cardiac gating in transverse and longitudinal planes. Standard
      cardiac views were derived from three-dimensional data, analyzed, and rated as
      follows: (1) not identifiable, (2) identifiable but inadequate for diagnosis, (3)
      adequate, and (4) excellent. Two-dimensional ultrasonography demonstrated better
      yields of diagnostically acceptable images of basic echocardiographic views (four
      chamber view, 100% for two-dimensional sonography versus 10 to 71% for three
      dimensional sonography; right ventricular outflow tract, 42% for two-dimensional
      versus 6 to 26% for three-dimensional ultrasonography; left ventricular outflow
      tract, 71% for two-dimensional versus 13 to 45% for three-dimensional
      sonography). In one subject three-dimensional ultrasonography was superior to two
      dimensional sonography in demonstrating an outflow tract. Aortic and ductal
      arches were not imaged with the two-dimensional technique but were available from
      the acquired three-dimensional volumes in 3 to 32% and 23%, respectively. False
      positive and false-negative findings were observed on three-dimensional
      ultrasonograms. Overall, compared to two-dimensional ultrasonography, non-cardiac
      gated three-dimensional sonography yielded inadequate reconstructed image quality
      of basic echocardiographic views (four-chamber view, right ventricular outflow
      tract, left ventricular outflow tract). Three-dimensional ultrasonography,
      however, shows potential for allowing nonechocardiographers to acquire some
      diagnostically acceptable views of the aortic and ductal arches.

PMID- 9623471
TI  - Lack of bioeffects of ultrasound energy after intravenous administration of FS069
      (Optison) in the anesthetized rabbit.
AB  - The current study was designed to provide a sensitive in vivo model to maximize
      the potential bioeffects (measured by hemolysis) of B-mode ultrasound energy in
      combination with FS069 (Optison). B-mode ultrasound energy was delivered to
      anesthetized male New Zealand white rabbits with a phased array 5 MHz transducer
      on a Hewlett-Packard Sonos 1500 ultrasonograph, with transmit level set to
      maximum (40 dB, approx 135 W/cm2). FS069 (Optison), latex particles in human
      albumin, or human albumin alone (vehicle) was infused via an ear vein at 0.6
      mL/kg. No statistically significant changes were noted in serum free hemoglobin
      or lactate dehydrogenase either over time or between groups.

PMID- 9623472
TI  - Hemodynamic factors affecting uterine artery Doppler waveform pulsatility in
      sheep.
AB  - Quantitative analysis of vascular resistance from the Doppler time-velocity
      waveform relies on measuring arterial pulsatility. However, input pressure
      waveform pulsatility, impedance, and resistance have all been found to effect
      artery flow waveform pulsatility in circulatory mathematic models and in
      umbilical sheep preparations in vivo. The present study used an in vivo sheep
      preparation to determine that embolization of the uteroplacental circulation and
      maternal angiotensin II administration caused changes in the uterine Doppler time
      velocity waveform pulsatility that were dependent on input pressure waveform
      pulsatility, fundamental impedance, and resistance changes. Uteroplacental
      vascular embolization increased vascular resistance and the uterine artery
      Doppler waveform resistive index; the mean component of flow (mean
      pressure/resistance) decreased. Decreased uterine artery Doppler resistive index
      occurred despite angiotensin II-induced vasoconstriction and increased vascular
      resistance because the pulse component of flow (pulse pressure/impedance)
      decreased.

PMID- 9623473
TI  - Simple cyst in the postmenopausal patient: detection and management.
AB  - The aims of our study were to determine the prevalence of simple ovarian cysts in
      asymptomatic postmenopausal patients and to investigate the natural history of
      these cysts by ultrasonographic follow-up examinations. Three thousand five
      hundred and eighty-five women participated in the volunteer pelvic cancer
      screening program. Entry criteria were as follows: postmenopausal, no clinical
      symptoms, and no previous gynecologic pathology. An anechoic, small cyst less
      than 5 cm in greatest diameter was classified as a simple ovarian cyst. A scoring
      system to determine malignant potential had been established previously. All
      simple cysts had a score of 2 or less and had a morphology typical of benign
      lesions. In the case of a positive finding, the patient would be seen at 3 to 6
      month intervals. The decision for surgical intervention was made by a private
      gynecologist or patient or if an interval change was noted. One thousand seven
      hundred and sixty-nine postmenopausal women (49.34% of all patients from the
      screening program) participated in this study. One hundred and sixteen simple
      cysts were found, with a prevalence of 6.6% in our population. Among those
      patients, 27 (23.28%) simple cysts resolved spontaneously, 69 (59.48%) have
      persisted, and 20 (17.24%) have been lost to follow-up study. Eighteen women
      (26.09%) with persistent simple ovarian cyst underwent surgery. No malignant
      ovarian conditions were identified. In conclusion, simple ovarian cysts are more
      common in postmenopausal women than previously was thought. This condition is
      very unlikely to be malignant and can be followed conservatively.

PMID- 9623474
TI  - Sonographic demonstration of Couinaud's liver segments.
AB  - The segmental localization of liver tumors is critical to planning appropriate
      resection. Couinaud's nomenclature is a surgically relevant system of hepatic
      segmental anatomy, which defines the liver segments by their relationships to
      vascular structures, hepatic ligaments, and the gallbladder. We demonstrate a way
      to accurately localize hepatic masses with sonography.

PMID- 9623475
TI  - Granulocytic sarcoma (chloroma) of the breast in an adolescent patient:
      ultrasonographic findings.

PMID- 9623476
TI  - Testicular torsion in neonates: importance of power Doppler imaging.

PMID- 9623477
TI  - Sonographic diagnosis of gallbladder perforation.

PMID- 9623478
TI  - Retrograde blood flow and dilatation of the varicocele on a color Doppler
      sonogram.

PMID- 9623479
TI  - Diagnosis of vasa previa with endovaginal color Doppler and power Doppler
      sonography: report of two cases.

PMID- 9623480
TI  - Neonatal citrobacter meningitis: neurosonographic observations.

PMID- 9623481
TI  - Second trimester prenatal diagnosis of congenital gastric outlet obstruction.

PMID- 9623482
TI  - Effects of pulsed ultrasound on the mouse neonate: hind limb paralysis and lung
      hemorrhage.

PMID- 9623483
TI  - Timing of exposures in ultrasonic hemorrhage of murine lung.

PMID- 9623484
TI  - Comparison of LHRH-peptidase and plasminogen activator activity in rat testis
      extracts.
AB  - Testicular LHRH-peptidase and testicular urokinase-type plasminogen activator are
      Sertoli cell-secreted proteases which display similar molecular properties.
      However, there is relatively little information regarding the substrate
      specificity and potential cross-reactivity of these enzymes. Testicular extracts
      were prepared from homogenates of whole rat testes and assessed by LHRH-peptidase
      assay, and by radial caseinolysis assays for plasminogen activator and plasmin
      like activity. Following partial purification of the protease activities in
      testicular extracts by gel filtration and ion-exchange chromatography, it was
      confirmed that testicular LHRH-peptidase and plasminogen activator are clearly
      separable. There was no detectable plasmin-like activity in the testicular
      extracts; however, the extracts were found to contain an inhibitor, or
      inhibitors, of both plasminogen activator and plasmin activity. In addition to
      LHRH and Gly6-substituted LHRH analogues, the partially purified LHRH-peptidase
      degraded both angiotensins I and II, but not the gonadotrophin-releasing-hormone
      associated peptide derived from the LHRH precursor molecule. These properties of
      the LHRH-peptidase provide further evidence that it is a testis-specific prolyl
      endopeptidase, involved in regulating and/or limiting peptide activity in the
      testis.

PMID- 9623485
TI  - Effect of culture, incubation and acrosome reaction of fresh and frozen-thawed
      ram spermatozoa for in vitro fertilization and intracytoplasmic sperm injection.
AB  - This study evaluated different sperm treatments for fertilization of sheep
      oocytes by intracytoplasmic sperm injection (ICSI) and in vitro fertilization
      (IVF). In Experiment 1, fresh and frozen semen was separated by Percoll
      centrifugation and incubated at 30 degrees C or 39 degrees C in HSOF or BSOF
      medium for 1 h before use for IVF or ICSI. For IVF, oocytes were inseminated and
      incubated with sperm for 30 min, 4 h and 19 h. Sperm were assessed for acrosome
      integrity after Percoll centrifugation and 1 h incubation, and those used for IVF
      were assessed after each period of exposure to the oocytes. Fertilization rates
      after ICSI were higher for fresh than for frozen-thawed sperm and were highest 19
      h after IVF with fresh or frozen-thawed sperm in the presence of HSOF at 30
      degrees C. In Experiment 2, fresh semen was separated by Percoll centrifugation
      and incubated for 5 h in HSOF, and the acrosome reaction was induced with
      lysophosphatidylcholine. Acrosome integrity was then assessed. Fertilization
      rates after ICSI were similar for acrosome-reacted and control spermatozoa. These
      results suggest that induction of the acrosome reaction in spermatozoa before
      ICSI is unnecessary, whereas a capacitating treatment of spermatozoa is required
      before IVF.

PMID- 9623486
TI  - Maternal constraint influences muscle fibre development in fetal lambs.
AB  - The objective was to examine myogenesis in two situations expected to be
      characterized by maternal constraint: (i) in fetuses due to be born in spring
      (n=10) or autumn (n=10); and (ii) in single (n=16) and twin (n=20) fetal lambs.
      Maternal constraint operating through limitation of placental size, as measured
      by placentome weight per fetus, was evident in each study. Although a lower
      placental weight did not influence body and muscle weights of fetuses due to be
      born in the spring or autumn, twins had lower body and muscle weights than
      singles. Fibre number and average fibre cross-sectional (CS) area were
      differentially affected by season and fetal number. The differences in muscle
      fibre morphology between spring- and autumn-born fetuses suggest that muscle
      fibre development was influenced by maternal constraint in the absence of an
      effect on fetal weight. The differences in muscle fibre number and CS area in
      particular muscles from twin and single fetuses suggest that more severe maternal
      constraint, reflected in a lower placental size per fetus, not only influences
      fetal weight but can also affect muscle development.

PMID- 9623487
TI  - Effect of oestradiol on ovarian oxytocin secretion rate and luteolysis in the ewe
      after ovarian auto-transplantation.
AB  - The release of ovarian oxytocin and uterine prostaglandin (PG)F2alpha in response
      to an oestradiol stimulus was investigated. On Day 15 post-oestrus, ten ewes with
      ovarian auto-transplants (n=5 per group) received an intra-muscular injection of
      either oestradiol benzoate (50 microg) or vehicle. Blood samples were collected
      from the ovarian and jugular veins at 30 and 0 min before, and at 15-min
      intervals up to 540 min after, injection. The secretion rate of ovarian
      progesterone remained elevated in four of five treated ewes and in all control
      ewes, indicating the presence of a functional corpus luteum. Peripheral
      oestradiol concentrations were significantly (P < 0.001) higher in treated than
      in control ewes. The number of ewes that released pulses of ovarian oxytocin > or
      =240 min following oestradiol benzoate injection was significantly (P < 0 05)
      greater than that in control ewes. Mean amplitude and area under both ovarian
      vein oxytocin and jugular-vein 15 keto-13,14 dihydro prostaglandin F2alpha (PGFM)
      pulses were significantly increased in the treated ewes. These findings
      demonstrate that the administration of exogenous oestrogen provides a positive
      stimulus for the release of ovarian oxytocin and uterine PGF2alpha in the ovarian
      auto-transplanted ewe.

PMID- 9623488
TI  - Epididymal compounds and antioxidants in diluents for the frozen storage of ram
      spermatozoa.
AB  - The epididymal compounds taurine, hypotaurine and inositol, and the antioxidants
      carnosine and ascorbic acid, were added to Tris-based diluents containing varying
      concentrations of glycerol, and their effect on the post-thaw motility
      characteristics and fertility of ram spermatozoa was examined. Overall, the post
      thaw motility characteristics of spermatozoa were better when semen was frozen in
      the presence rather than in the absence of glycerol. Only taurine protected
      spermatozoa during cryopreservation; the presence of 25 mM or 50 mM taurine
      significantly improved the post-thaw percentage of motile spermatozoa but this
      had no effect on fertility after cervical or laparoscopic insemination of ewes.
      Increasing the concentration of taurine to more than 100 mM significantly reduced
      the percentage of motile spermatozoa, compared with the lower concentrations of
      the amino acid. The presence of more than 50 mM carnosine or ascorbic acid
      significantly reduced all motility characteristics compared with the control
      diluent. Given that hypotaurine, carnosine, or ascorbic acid did not improve post
      thaw motility, the cryoprotective effect of taurine may be attributable to its
      osmoregulation rather than to its antioxidant properties.

PMID- 9623489
TI  - Micromolar concentration of pentoxifylline improves development in vitro of
      hamster 8-cell embryos: confirmation of biological viability by embryo transfer.
AB  - The influence of the sperm motility stimulant pentoxifylline (PF) on
      preimplantation embryo development in hamsters was evaluated. Eight-cell embryos
      were cultured in hamster embryo culture medium (HECM)-2, with or without PF
      (0.023-3.6 mM). There was 90%, 37% and 29% inhibition of blastocyst development
      by 3.6 (used for human sperm), 0.9 and 0.45 mM PF, respectively. However, 23
      microM PF (exposed to hamster oocytes during IVF) significantly (P < 0.05)
      improved blastocyst development (63.6% v. 51.8%); morulae development was,
      however, not curtailed by 0.45 mM or 0.9 mM PF (51.8%+/-6.0 or 50.5%+/-11.3,
      respectively). Post-implantation viability of PF-treated embryos was assessed by
      embryo transfer; 43% of 80 PF-treated embryos implanted compared with 40% of 79
      control embryos. Of the 9 recipients, 6 females delivered pups (19, i.e. 16% of
      transferred embryos or 53% of implanted embryos). These data show that in
      hamsters, continuous presence of PF at 0.45-3.6 mM is detrimental to 8-cell
      embryo development whereas 23 microM PF improves the development of embryos to
      viable blastocysts which produce live offspring.

PMID- 9623490
TI  - Is the acrosome reaction a prerequisite for sperm incorporation after intra
      cytoplasmic sperm injection (ICSI)?
AB  - There is debate as to whether the acrosome reaction is necessary for sperm
      incorporation after intra-cytoplasmic sperm injection (ICSI). Ultrastructural
      evidence is presented to show that the acrosome reaction could occur in the
      ooplasm before sperm incorporation in mature human oocytes or the acrosome could
      be discarded intact before sperm incorporation in immature oocytes, matured in
      vitro. Both germinal vesicle and growing follicular oocytes showed sperm
      chromatin decondensation, with discarded acrosomes close to the sites of
      incorporation, and were able to form male pronuclei. This is probably the first
      report of microfertilization of a growing oocyte with a reticulate nucleolus by
      ICSI. The acrosome reaction, when it occurs, is preceded by acrosome swelling and
      is followed by vesiculation of surface membranes exposing the inner acrosome
      membrane, as observed on the surface of the zona during IVF or in the
      perivitelline space after subzonal sperm injection. These sperm were probably
      capacitated at the time of ICSI. There was subtle evidence of leaching of the
      acrosomal matrix from intact discarded acrosomes and from partially depleted
      acrosomes attached to decondensing spermheads. These sperm were probably not
      fully capacitated at the time of ICSI. It is concluded that both the acrosome
      reaction and acrosome deletion are possible prerequisites to sperm incorporation
      after ICSI.

PMID- 9623491
TI  - Effect of undernutrition of ewes from the time of mating on fetal ovarian
      development in mid gestation.
AB  - Ewes were fed either 150% (High, H) or 50% (Low, L) of their energy requirements
      for maintenance of liveweight during early gestation. Effects of maternal
      nutrition on fetal ovarian size, histological structure and steroidogenic
      capacity were studied at Day 47 and on ovarian size and structure at Day 62 of
      gestation. At Day 47 of gestation, there were significantly higher concentrations
      of oogonia in the ovaries of L fetuses than H fetuses (105.9 v. 76.9 germ cells
      mm(-2); s.e. 4.94; P < 0.001). The capacity of the ovaries to secrete oestradiol
      (pg/ovary/24 h) at Day 47 was not affected by treatment when they were incubated
      either with (H, 773; L, 740; s.e. 179; not significant, n.s.) or without (H, 260;
      L, 290; s.e. 92.7; n.s.) ovine luteinizing hormone (oLH). At Day 62 of gestation,
      the process of germ cell degeneration was less advanced in L than H fetal
      ovaries, as indicated by higher oocyte concentrations in the former (68.4 v. 48.6
      germ cells mm(-2); s.e. 3.85; P < 0 01). There was a greater percentage of
      meiotic cells in L ovaries (76.5 v. 18.6; s.e. 5.82; P < 0.001). It is concluded
      that undernutrition of the ewe from the time of mating significantly retards
      ovarian development in fetal ovaries.

PMID- 9623492
TI  - Leukaemia inhibitory factor stimulates proliferation of prospermatogonial stem
      cells.
AB  - The effect of leukaemia inhibitory factor (LIF) on the proliferation of
      prospermatogonial stem cells was tested in vitro. Pieces of 3-day-old rat testis
      were cultured in the presence of a range of doses of LIF alone or in combination
      with 1 ng mL(-1) seminiferous growth factor (SGF). Stimulation of the
      proliferative activity of quiescent prospermatogonia was detected
      immunocytochemically with a cell proliferation kit. After 24 h culture, LIF
      significantly increased the percentage of labelled prospermatogonia, with the
      peak of activity at 20 pg mL(-1). The combination of LIF and SGF resulted in a
      decrease in DNA synthetic activity of the germ cells. Hence, LIF and SGF play a
      role in local regulation at the onset of spermatogenesis in the rat testis.

PMID- 9623493
TI  - Embryo development and placentome formation during early pregnancy in red deer.
AB  - Early embryo development and placentome formation were assessed in red deer
      between Days 27 and 55 of gestation. Uteri were collected from 12 pregnant hinds
      in which mating was observed following a synchronized oestrus, and the tissues
      retained for measurements and histological processing for light microscopy.
      Twelve embryos were recovered with mean embryo weights increasing from 0.02+/
      0.01 g at Day 27 to 7.56+/-1.39 g at Day 55 of gestation. Similarly, crown-rump
      lengths increased from 5.7+/-0.7 mm to 55.3+/-5.9 mm over this period. The
      trophoblast had extended throughout both uterine horns and gastrulation was
      completed by Day 27. Limb buds were apparent by Day 34, and by Day 48 the
      phalanges had separated into hooves and dew claws. Plaques were evident on the
      trophoblast at Day 34 and, by Day 41, placentomes had formed adjacent to the
      embryo. These placentomes grew in size as pregnancy advanced; by Day 55 most
      caruncles had formed placentomes. It is therefore confirmed that placentome
      formation occurs at about the sixth week of gestation. These results indicate
      that embryo growth and placentome formation in red deer are generally typical of
      that observed in other ruminants.

PMID- 9623494
TI  - Postnatal development and differentiation of myofibres in functionally diverse
      porcine skeletal muscles.
AB  - Marked changes in muscle function occur after birth, with the response being
      dependent on developmental stage. Therefore, postnatal cellular ontogeny of
      functionally distinct skeletal muscles was investigated in the pig, a large
      mammal born at a relatively advanced stage of development. Assessment of myofibre
      contractile (type I slow/type II fast) and metabolic (oxidative/glycolytic)
      properties at Days 0, 2, 5 and 14 revealed type-specific differences in
      hypertrophy and differentiation. Type I fibre proportions increased significantly
      in soleus and diaphragm, especially between Days 0 and 5, and rhomboideus showed
      a similar trend, but in longissimus there was a slight decrease during Days 0-2.
      Cytochrome oxidase activity was relatively high and similar among myofibres in
      all muscles at birth, and fibres with low activity were not detected until Day 5.
      In contrast with previous reports, glycolytic fibres were present in all muscles
      at birth; postnatal changes in alpha-glycerophosphate dehydrogenase activity were
      both muscle- and myofibre-specific. Hence, although myosin ATPase activity and
      metabolic properties of porcine myofibres are well developed at birth, they
      continue to mature postnatally. This suggests that postnatal muscle development
      can be modulated by extrinsic factors, even in mammals born at a relatively
      advanced stage of development.

PMID- 9623495
TI  - Vitrification of in vitro produced bovine embryos at different ages using one-
      and three-step addition of cryoprotective additives.
AB  - The effect of embryo age on development and ratio of live: dead cells after
      vitrification and warming was examined. One-step and three-step addition of
      cryoprotectants in vitrification solution (40% ethylene glycol, 0.3 M trehalose
      and 12% polyvinylpyrrolidone) were compared using in vitro produced (IVP) bovine
      blastocysts and expanded blastocysts. Rates of development and hatching were
      74.2% and 41.9% for Day 7, 57.8% and 23.8% for Day 8, 33.7% and 6.1% for Day 9
      embryos with one-step addition. In three-step addition, those rates were 86.2%
      and 77.3% for Day 7, 72.3% and 39.0% for Day 8, 47.3% and 10.5% for Day 9
      embryos. Day 7 embryos showed highest (P < 0.01) development and hatching rates
      with one exception. Hatching rate of Day 7 embryos with three-step addition was
      higher (P < 0.01) than with one-step addition. The ratio of live:dead cells
      differed between one-step (94%) and three-step (97%) additions for Day 7 embryos
      (P < 0.05). The results indicate the higher resistance of younger IVP bovine
      embryos against vitrification and the potential for three-step addition of
      cryoprotectants to yield a higher survival rate after warming than with one-step
      addition.

PMID- 9623496
TI  - Relation between the heavy chain complementarity region 3 characteristics and
      rheumatoid factor binding properties.
AB  - Among the rheumatoid factors (RFs), monospecific and polyspecific types can be
      distinguished. However the molecular basis responsible for their different
      specificity is not well understood. In a previous report, we have shown that the
      binding of the majority of the polyspecific antibodies is salt-sensitive. No
      binding to IgG was observed under high ionic strength (0.3-0.5 M NaCl). This salt
      sensitivity was only observed for 18% of the monospecific RFs. Here, we have
      analyzed 14 RFs representing the 3 different groups (6 salt-insensitive
      monospecific, 4 salt-sensitive monospecific and 4 salt-sensitive polyspecific
      RFs). By analysis of the amino acid composition and the distribution of polar and
      non-polar residues of their heavy chain complementarity-determining region 3 (H
      CDR3) in relation to mono/polyspecificity, salt-sensitivity and reactivity
      against human IgG subclasses, we have identified common structural features
      responsible for their different binding properties. Salt-sensitive RFs (mono as
      well as polyspecific antibodies) were characterized by long H-CDR3's (15.3+/-2.7)
      that contained large numbers of hydrophilic residues such as arginine and serine,
      while salt-insensitive RFs had more hydrophobic H-CDR3's of smaller length
      (11.3+/-2.4). In addition, for the monospecific RFs, remarkably similar
      hydrophilicity H-CDR3 profiles were found that were correlated with their
      specificity for IgG subclasses. These observations confirm the importance of the
      H-CDR3 for the binding of RFs to IgG. Furthermore, on the basis of their shorter
      H-CDR3's and their rather unique H-CDR3 hydrophilicity profiles, it is likely
      that the majority of the monospecific RFs should be considered as a group of RFs
      that is independent of the polyspecific RF repertoire.

PMID- 9623497
TI  - Correlation between IgG anti-type II collagen levels and arthritic severity in
      murine arthritis.
AB  - This study examines the relationship between the serum levels of IgG antibodies
      to heterologous and homologous type II collagen and the subsequent arthritic
      severity in a collagen induced arthritis model. Arthritis was induced in DBA-1
      mice using intradermal injections of heterologous type II collagen in Freunds
      complete adjuvant, the time of arthritis onset was noted and the severity was
      monitored regularly. Serum samples were taken and IgG levels of anti-heterologous
      and homologous type II collagen were analyzed both pre and post arthritis onset.
      We observed that post induction/pre arthritic serum IgG anti-heterologous and
      homologous type II collagen levels showed a significant correlation (both p <
      0.01) with the severity of the arthritis that subsequently developed. Mice with
      early arthritis showed a highly significant correlation (p < 0.002) between sera
      IgG anti-homologous type II collagen levels and arthritic severity, a lesser
      correlation was also apparent between anti-heterologous type II collagen titres
      and arthritic severity (p < 0.05). The high levels of correlation observed in
      this study between anti-type II collagen titres and arthritic severity before
      actual onset of arthritis, clearly suggest that the magnitude of the initial
      humoral response to type II collagen plays a crucial role in determining the
      resultant arthritic severity. This observation is only apparent due to the use of
      an arthritis susceptible inbred mouse strain, which removes variables such as H-2
      restriction, antigen processing/presentation and possible complement
      deficiencies, and the early time scale of the analysed sera samples.

PMID- 9623498
TI  - IgG2a antibodies non-specifically delay the onset of diabetes in NOD mice.

PMID- 9623499
TI  - Iodine is essential for human T cell recognition of human thyroglobulin.
AB  - Here we describe for the first time that recognition by human T cells of human
      thyroglobulin depends upon its iodine content. We have examined the proliferation
      of lymphocytes from blood of autoimmune thyroiditis patients and normal
      individuals to thyroglobulin preparations containing different amounts of iodine.
      A minimal degree of iodination was required to elicit the proliferative response
      of both patients and normal individuals since thyroglobulin preparations
      containing no detectable iodine did not induce proliferation. A non-iodinated
      thyroglobulin preparation that was iodinated in vitro produced significant
      proliferation of both patient and normal lymphocytes. Addition of IL-2 to the
      culture medium enhanced proliferation but did not change the pattern of response.

PMID- 9623500
TI  - T cell interactions with extracellular matrix proteins in patients with thyroid
      associated ophthalmopathy.
AB  - Although thyroid-associated ophthalmopathy (TAO) is now generally accepted as an
      autoimmune inflammatory disorder of the extraocular muscles and the orbital
      connective tissue, its aetiopathogenesis remains poorly understood. Recent data
      indicate that impaired interactions between T cells and extracellular matrix
      (ECM) proteins may play an important role in development and maintaining of an
      inflammatory process. We report here results of the study focusing on
      interactions between T lymphocytes and collagen-I (Coll-I), collagen-IV (Coll
      IV), fibronectin (FN), laminin (LM) in patients with TAO. Using a standard
      peripheral blood mononuclear cells (PBMC) proliferation assay, we observed a
      markedly enhanced T cell response to Coll-I in patients with active TAO (mean
      SI=4.5). The proliferatory response to Coll-I was significantly greater (Wilcoxon
      test; p < 0.001) than in normal subjects (mean SI=1.88), patients with stable TAO
      (mean SI=2.05) and patients with thyroid autoimmune diseases (AITD) without
      ophthalmopathy (mean SI=2.49). PBMC stimulation by Coll-I is likely to be antigen
      dependent requiring engagement of the T cell receptor with collagen peptides,
      rather than mediated via integrins. The percentage of circulating CD29+ (beta1
      integrin chain) T cells was not increased in patients with active TAO.
      Additionally in the assay of costimulation of CD3-mediated proliferation, we
      found that peripheral blood T cells from patients with TAO and AITD were
      costimulated only by FN. On the other hand a markedly enhanced costimulation of
      CD3-mediated proliferative responses by Coll-I, Coll-IV, FN and LM were observed
      in a retrobulbar T cell line. We conclude that abnormalities in T cell
      interactions with ECM proteins, especially Coll-I may play a role in the
      pathogenesis of TAO.

PMID- 9623501
TI  - Anti-neutrophil cytoplasm autoantibodies (ANCA). The need for specific and
      sensitive assays.
AB  - Anti-neutrophil cytoplasm antibodies (ANCA) are a group of autoantibodies
      primarily associated with systemic vasculitis. Hitherto, the method of choice for
      ANCA detection has been indirect immunofluorescence (IIF). By this method two
      major patterns can be seen: a cytoplasmic pattern (cANCA) or a perinuclear
      pattern (pANCA). The cANCA pattern is most often caused by antibodies directed
      against proteinase-3 (PR3) and in rare cases it is caused by anti-myeloperoixdase
      (MPO) antibodies. The pANCA pattern can de caused by antibodies directed against
      a large group of proteins i.e. MPO, lactofenin and bactericidal/permeability
      increasing protein. Often there is a discrepancy between the results obtained by
      IIF and those reported from the use of assays with purified antigens. This causes
      confusion. Until now only anti-PR3 and anti-MPO have been found of any clinical
      value. Therefore, it would be more proper to use assays with these highly
      purified antigens instead of an unspecific method like IIF.

PMID- 9623502
TI  - The role of glycosylation in autoimmune disease.
AB  - Oligosaccharide structures play a key role in the antigenicity of a number of
      clinically important antigens such as blood group determinants. Interest in
      glycobiology has increased dramatically amongst immunologists during the last few
      years due to the fact that oligosaccharides also play a central role in adhesion
      and homing events during inflammatory processes (1), comprise powerful
      xenotransplantation antigens (2), and may provide targets for tumor immunotherapy
      (3). Additionally, alterations in glycosylation are now known to occur in a
      number of autoimmune diseases. This review will first discuss some general
      aspects of protein glycosylation and then explore some of the autoimmune diseases
      in which the role of glycosylation has been examined.

PMID- 9623503
TI  - To E or not to E? Can an IL-4-induced B cell choose between IgE and IgG4?
AB  - Parasite immunologists had known for some time that IgE-mediated hypersensitivity
      reactions are rare in patients with chronic helminth infections, even though
      basophils and mast cells in these patients are sensitized with antiparasite IgE
      and exposed, often continuously, to parasite antigens. The inhibition of allergic
      reactivity in chronic helminth infections is mainly due to IgG4 'blocking
      antibodies' in the serum of the infected individual. IgG4 do not fix complement
      and bind weakly to Fcgamma receptors. Thus, antigen binding by IgG4, unlike IgE,
      is likely to have no or minimally harmful consequences. The discovery that,
      similar to IgE, expression of IgG4 is IL-4-dependent and is an intermediate step
      in sequential switching from IgM to IgE makes it imperative to understand how the
      two isotypes are coregulated and whether the two responses can be uncoupled,
      selectively boosting IgG4 over IgE. The ultimate goal is to apply to allergy the
      lesson we learnt from helminth infections.

PMID- 9623504
TI  - Organs from animals for man.
AB  - In the following review some of the problems of xenotransplantation shall be
      discussed, based on the few experimental data available so far and on reports in
      the literature describing investigations which may be of importance for
      xenotransplantation. The impact of gravity on the upright posture of man versus
      almost all other mammals, the dysfunction between enzymes and hormones in
      different species and the lack of interactions between interleukins, cytokines
      and vasoactive substances will be taken into consideration. The question must be
      asked whether different levels of carrier molecules or serum proteins play a role
      in the physiological network. Even though the development of transgenic animals
      or other imaginative manipulations may lead to the acceptance of any type of
      xenografted organ, it has to be established for how long the products of the
      xenografts are able to act in the multifactorial orchestra. We are far from
      understanding xenogeneic molecular mechanisms involved in toxicity, necrosis and
      apoptosis or even reperfusion injury and ischemia in addition to the immediate
      mechanisms of the hyperacute xenogeneic rejection. Here, cell adhesion, blood
      clotting and vasomotion collide and bring micro- and macrocirculation to a
      standstill. All types of xenogeneic immunological mechanisms studied so far were
      found to have a more serious impact than those seen in allogeneic
      transplantation. In addition we are now only beginning to understand that so
      called immunological parameters in allogeneic mechanisms act also in a true
      physiological manner in the xenogeneic situation. These molecular mechanisms
      occur behind the curtain of hyperacute, accelerated, acute or chronic xenograft
      rejection of which only some folds have been lifted to allow glimpses of part of
      the total scene. Other obstacles are likely to arise when long-term survival is
      achieved. These obstacles include retroviral infections, transfer of prions and
      severe side effects of the massive immunosuppression which will be needed. Moral,
      ethical and religious concerns are under debate and the species-specific
      production of proteins of the foreign donor species developed for clinical use
      suddenly appears to be a greater problem than anticipated.

PMID- 9623505
TI  - Biochemical characterization of Pru a 2, a 23-kD thaumatin-like protein
      representing a potential major allergen in cherry (Prunus avium).
AB  - BACKGROUND: The prevalence of allergy to fruits and vegetables increased with
      pollinosis over the last 10 years. So far, clusters of hypersensitivity have been
      established and corroborated by the molecular characterization of individual
      cross-reacting allergens. Several case studies demonstrated the existence of
      allergic reactions to fruits of the subfamily Prunoideae (apricots, cherries,
      plums and peaches). Here, we present the characterization of a major allergen in
      cherry. METHODS: Characterization was performed using IgE immunoblotting and
      immunoblot inhibition, N-terminal sequencing, mass spectroscopy analysis and PCR
      based cDNA cloning. RESULTS: A 23-kD protein was identified as IgE-binding
      component. As all cherry-extract-reactive sera displayed IgE-binding to this
      band, it was designated a major allergen from Prunus avium (Pru a 2). Sequencing
      the corresponding cDNA identified Pru a 2 as a thaumatin-like protein belonging
      to the group 5 of pathogenesis-related proteins. CONCLUSIONS: A thaumatin-like
      protein in cherry has been identified as a major allergen (Pru a 2). Homologous
      proteins from the thaumatin family share sequence similarities and should
      therefore be checked for the capability to elicit an IgE-mediated allergic
      reaction.

PMID- 9623506
TI  - Alkaline serine proteinase: a major allergen of Aspergillus oryzae and its cross
      reactivity with Penicillium citrinum.
AB  - BACKGROUND: Aspergillus species are common indoor airborne fungi and have been
      considered as causative agents of human allergic disorders. However, allergens of
      different Aspergillus species have not been effectively characterized. The object
      of this study was to identify and characterize IgE-binding components of
      Aspergillus oryzae. METHODS: Allergens of A. oryzae were identified by immunoblot
      analysis using sera from asthmatic patients. The N-terminal amino acid sequences
      of allergens thus identified were determined by Edman degradation. The antigenic
      and the allergenic cross-reactivities between allergens of different fungi were
      analyzed by immunoblotting and immunoblot inhibition analysis, respectively,
      using a monoclonal antibody (MoAb) 55A against the 33-kD major allergen of
      Penicillium citrinum and a mixture of IgE-containing asthmatic serum samples.
      RESULTS: Thirteen components of A. oryzae ranging in apparent molecular weight
      from 16 to 42 kD react with IgE antibodies. A 34-kD component that showed intense
      IgE-binding reactivity and was detectable in the highest frequency in our
      asthmatic serum samples tested was considered a major allergen of A. oryzae. The
      34-kD component also reacted with MoAb 55A. Results from immunoblot inhibition
      studies also demonstrated the IgE cross-reactivity between the 34-kD major
      allergens of A. oryzae and P. citrinum. In addition, the sequence of the N
      terminal 18 amino acid residues of the 34-kD major allergen of A. oryzae was
      found to be identical to that of the alkaline serine proteinase from the same
      Aspergillus species. CONCLUSION: The 34-kD major allergen of A. oryzae is an
      alkaline serine proteinase. There is IgE cross-reactivity between the major
      serine proteinase allergens of A. oryzae and P. citrinum.

PMID- 9623508
TI  - Molecular cloning and expression of cynomolgus monkey interleukin-1beta cDNA.
AB  - The cynomolgus monkey cDNA encoding interleukin-1beta (IL-1beta) was molecularly
      cloned by the reverse transcription polymerase chain reaction from a cDNA library
      of adherent splenocytes stimulated with lipopolysaccharides. The sequence
      analysis showed that the monkey IL-1beta cDNA encodes a protein of 268 amino
      acids and displays a high degree (90%) of homology with the human counterpart.
      Substitution of amino acids resides mainly in the leader sequences of IL-1beta
      when compared with those of human IL-1beta. This cloned monkey IL-1beta cDNA was
      used to express in Escherichia coli as a fusion protein with thioredoxin and in
      insect cells infected with a recombinant baculovirus after molecular modification
      where monkey IL-1beta signal sequences were placed prior to the mature sequences
      of IL-1beta for efficient secretion in insect cells. Recombinant monkey IL-1beta
      expressed in both systems was shown to react with rabbit antihuman IL-1beta
      antiserum by Western blot analysis and to have the biological activity of IL
      1beta in a bioassay.

PMID- 9623507
TI  - Role of antigen-induced cytokine release in atopic pruritus.
AB  - In order to further evaluate the role of cytokines in the induction of atopic
      pruritus, leukocytes from 10 atopic eczema patients or 10 nonallergic controls
      were stimulated in vitro with mite or birch pollen antigen for 1 and 4 days.
      Subjects were prick-tested with the supernatants, and whealing and itching were
      evaluated 20 and 60 min later. The supernatants were also examined for the
      contents of GM-CSF, IL-2, IL-6 and IL-8 by ELISA and TNFalpha. Two hours prior to
      testing, the antihistamine cetirizine (20 mg) or a placebo tablet were given to
      the patients according to a randomized, double-blind study protocol. After
      pricking with antigen-stimulated leukocyte supernatants, 6 of 10 patients but no
      controls reacted mostly at 20 min with whealing and/or pruritus. In the
      cetirizine-treated group, no decrease in these skin reactions was seen compared
      to placebo. Analysis for cytokines showed increased levels of IL-8 in allergen
      stimulated samples, with no correlation to the induction of itching or whealing
      by these supernatants. IL-6 levels were low and variable, and GM-CSF, IL-2 and
      TNFalpha levels were always below standard values. These data show that
      leukocytes selectively release IL-8 in response to in vitro antigen stimulation.
      They furthermore provide additional support for the concept that as yet to be
      identified products play a role in atopic pruritus.

PMID- 9623509
TI  - Effects of anti-IL-5 monoclonal antibody on the murine model of nasal allergy.
AB  - IL-5 is known to be closely related to the infiltration, activation and
      proliferation of eosinophils. In this study, we evaluated the in vivo effects of
      anti-IL-5 monoclonal antibody (mAb) in the murine model of nasal allergy. The mAb
      treatment inhibited the antigen-induced late phase eosinophilia, but had no
      effects on the number of basophilic cells. It also inhibited early phase nasal
      symptoms, and tended to inhibit histamine hypersensitivity. These findings
      suggest that IL-5 plays an important role in the pathogenesis of allergic nasal
      disorders.

PMID- 9623510
TI  - IL-8 and the activation of eosinophils and neutrophils following nasal allergen
      challenge.
AB  - BACKGROUND: A growing body of evidence suggests that proinflammatory cytokines
      play a role in allergic inflammation by attracting and activating inflammatory
      cells. In this study, we have investigated the relationship between interleukin-8
      (IL-8) in nasal lavage fluid and the local activation of eosinophils and
      neutrophils following nasal allergen challenge of allergic patients. METHODS:
      Nasal challenges were performed with grass pollen extract in 14 allergic patients
      and 5 nonallergic controls. Nasal lavage fluid was collected repeatedly for 10 h,
      and the levels of eosinophil cationic protein (ECP) and myeloperoxidase (MPO)
      were used as markers of eosinophil and neutrophil activation, respectively. The
      levels of these molecules were compared with that of IL-8 in nasal lavage fluid.
      RESULTS: Allergen challenge of allergic patients produced a significant late
      phase increase in the levels of ECP and MPO. Furthermore, the level of MPO showed
      a highly significant correlation with the level of IL-8 in lavage fluid (r = 0.8,
      p< 0.0001), whereas there was no significant relationship between the levels of
      ECP and IL-8. CONCLUSION: Interestingly, our findings suggest that both
      eosinophils and neutrophils are activated following nasal allergen challenge. In
      addition, our results are consistent with the hypothesis that IL-8 acts as a
      chemoattractant/activator of neutrophils during the late phase of the allergic
      inflammation. In contrast, we were not able to demonstrate any significant
      relationship between the level of IL-8 in lavage fluid and the activation of
      eosinophils.

PMID- 9623511
TI  - IgG antibody subclasses, tumor necrosis factor and IFN-gamma levels in patients
      with type II lepra reaction on thalidomide treatment.
AB  - A group of 9 Mexican lepromatous leprosy patients was studied at the beginning of
      a type II reaction (erythema nodosum leprosum, ENL) and after 1 or 2 months of
      thalidomide treatment. ENL patients at the onset of the reaction had slightly
      higher amounts of anti-Mycobacterium leprae IgG1 and IgG2 antibodies, compared to
      similar lepromatous patients that did not develop ENL. Neither these antibody
      levels nor IgM and the other IgG subclasses were importantly modified after
      thalidomide treatment. Serum TNF was significantly higher in the patients that
      developed ENL compared to those that did not develop the reaction. TNF levels
      were slightly decreased after 1 month of thalidomide treatment and significantly
      decreased after 2 months of treatment. Serum IFN-gamma was significantly lower in
      patients at the onset of ENL and was increased after 1 and 2 months of
      thalidomide treatment.

PMID- 9623512
TI  - Inhibition of pulmonary eosinophilia does not necessarily prevent the airway
      hyperresponsiveness induced by Sephadex beads.
AB  - BACKGROUND: The Lewis rat among highly inbred strains exhibits significant airway
      hyperresponsiveness (AHR) following intravenous administration of Sephadex G-200
      (Sephadex). The aim of this study was to investigate the association of Sephadex
      induced AHR with changes in airway inflammation in Lewis rats. METHODS: A
      suspension (0.5 mg/ml/rat) of Sephadex was intravenously administered to male
      Lewis rats on days 0, 2 and 5. Measurement of airway responsiveness to serotonin,
      bronchoalveolar lavage (BAL) and histological study were performed on day 2-11.
      RESULTS: Significant AHR induced by Sephadex was recognized on day2 (p < 0.05),
      and AHR reached a maximum on day 7 (p < 0.001). In the BAL study, eosinophils
      increased on day2 (p < 0.01) with a peak on day 5 (p < 0.05). In the histological
      study, we found Sephadex beads trapped in small arteries of the lung and
      granulomatous arteritis on day 2 or later. Pulmonary granulomas, horseshoe-shaped
      multinuclear giant cells, eosinophils and goblet cell hyperplasia were observed
      on day 2, and the degree became intense on day 5-7. GCC-AP0341 (10 mg/kg, i.p. x
      3) inhibited the recruitment of eosinophils in BAL fluid and in lung tissue, but
      it did not inhibit AHR. The compound also inhibited pulmonary granulomas and
      goblet cell hyperplasia. CONCLUSION: The mechanism of Sephadex-induced AHR may
      not be directly associated with inflammatory changes such as recruitment of
      eosinophils, pulmonary granulomas and hyperplasia of goblet cells in rats.

PMID- 9623513
TI  - Predominant implication of IL-5 in acute eosinophilic pneumonia: comparison with
      chronic eosinophilic pneumonia.
AB  - BACKGROUND: Acute eosinophilic pneumonia (AEP) is a rare disease with unknown
      etiology. To examine pathophysiology of AEP we measured the cell number of
      eosinophils and eosinophil active cytokines in the peripheral blood and
      bronchoalveolar lavage fluid (BALF) of AEP patients and compared the levels with
      those measured in chronic eosinophilic pneumonia (CEP) patients. METHODS: Cell
      number of eosinophils in peripheral blood and BALF from patients with AEP (n = 3)
      and CEP (n = 3) were measured. Eosinophil active cytokines in serum and BALF from
      the patients were measured using ELISA. RESULTS: Eosinophil cell number in
      peripheral blood was 274-1,377/mm3 in AEP and 526-2,500/mm3 in CEP. The
      percentages of BALF eosinophils were high in AEP and CEP. Eosinophilia
      disappeared after methylprednisolone pulse therapy (1 g for 3 days) in AEP,
      however the cell number of eosinophils gradually increased after
      methylprednisolone pulse therapy and then spontaneously decreased to within
      normal range without any further medication. The concentrations of IL-5 in AEP
      were very high in serum and in BALF, however the concentrations in CEP were low
      in serum and BALF. CONCLUSION: AEP is a disease in which eosinophil active
      cytokine IL-5 is predominantly involved; CEP is not. The factors involving
      eosinophil infiltration to inflammatory loci differ between AEP and CEP.

PMID- 9623514
TI  - Oral tolerance is not influenced by oral application of oil-emulsified proteins.
AB  - A 2-week program of feeding protein antigens as an oil-in-water emulsion to naive
      mice elicited a significant serum IgG antibody response, whereas their aqueous
      preparations did not at all. The unresponsive immune state that had been
      developed after feeding aqueous antigen was not disturbed by subsequent oral
      challenge with the same antigen in the presence of oil. These results suggest
      that the principle of oral tolerance is a feasible strategy for prophylaxis of
      hypersensitization to protein antigens, where protein tolerogens, in this case,
      are to be given without any additives at their first introduction.

PMID- 9623515
TI  - Treatment of Graves' disease in children and adolescents.

PMID- 9623516
TI  - Radioiodine treatment of Graves' disease in young people.
AB  - In Europe young patients with Graves' disease are usually treated with
      antithyroid drugs initially, then if hyperthyroidism recurs after a prolonged
      course of such medication, they are offered definitive treatment by subtotal or
      total thyroidectomy. Neither of these forms of treatment is free from problems.
      Impressed with the simplicity and safety record of radioiodine therapy, we have
      treated 8 young patients with radioiodine. The patients all presented with
      typical Graves' disease and relapsed after 18-24 months of treatment with
      antithyroid drugs. They were then given the option of a further course of
      antithyroid medication or definitive treatment with radioiodine or surgery. Those
      who opted for radioiodine were treated with 131iodine in a dose of 300 MBq with
      the intention of ablating the thyroid. Antithyroid medication was resumed for 4-6
      months and then withdrawn. Four patients became hypothyroid after a single dose
      of radioiodine but 4 needed a second dose. All became hypothyroid within 2 years.
      No adverse effects were observed, in particular no patient showed any
      deterioration in their eye disease. Radioiodine offers a simple, effective and
      inexpensive method of treatment for Graves' disease in young patients. There are
      no immediate adverse effects and, although some theoretical concerns remain, to
      date the long-term safety record of thyroid ablation is excellent and the
      potential risks seem to us to be outweighed by the advantages. Even when a
      moderately high initial dose of radioiodine is used, a second dose may be needed.

PMID- 9623517
TI  - Opioid blockade effect on insulin beta-cells secretory patterns in polycystic
      ovary syndrome. Oral glucose load versus intravenous glucagon bolus.
AB  - In order to evaluate the involvement of endogenous opiates in the insulin
      disorders of polycystic ovary syndrome (PCOs) a total of 25 PCOs women and 11
      normo-ovulatory controls were studied by comparing the effect of a chronic opioid
      blockade on beta-cells responsiveness to oral glucose load and to intravenous
      glucagon bolus. Each patient, studied on follicular phase, underwent to oral
      glucose tolerance test (OGTT), and, 2 days later, to a glucagon intravenous bolus
      (1 mg); these tests were then repeated after 6 weeks of naltrexone treatment (50
      mg orally). Naltrexone treatment did not modify the insulin secretory patterns of
      control subjects, whereas the same therapy significantly reduced, in
      hyperinsulinemic PCOs women, the beta-cell hyperresponsiveness both to oral
      glucose load and to intravenous glucagon (p < 0.05 and p < 0.01, respectively),
      even if with different mean percent decrease (32% OGTT vs. 45% glucagon, p <
      0.05). Moreover, normoinsulinemic PCOs patients showed a slight, but not
      significantly increase in the beta-cells response to OGTT after opioid blockade,
      whereas, in the same situation, the insulin release after glucagon bolus was
      significantly reduced (p < 0.01). Chronic opioid blockade did not modify
      gonadotropins, steroids and SHBG levels in either group. Our data show that
      naltrexone treatment is able to reduce the beta-cell response to a direct
      intravenous secretagogue stimulus in all PCOs patients, while only in
      hyperinsulinemic PCOs subjects the same treatment is effective in reducing the
      exaggerated insulin secretion after oral glucose load. The reason for such a
      discrepancy could be ascribed to a different effect of opioids on first- and
      second-phase insulin secretion, or, alternatively, to an involvement of other
      secretagogue factors, such as glucoincretins.

PMID- 9623518
TI  - Effects of growth hormone replacement therapy on IGF-related parameters and on
      the pituitary-gonadal axis in GH-deficient males. A double-blind, placebo
      controlled crossover study.
AB  - It has been suggested that growth hormone (GH) may play a regulatory role in male
      reproductive function. To express full anabolic effect in immature boys
      testosterone apparently requires the presence of GH. In GH-deficient adults, GH
      replacement therapy exerts a variety of anabolic actions, some of which are
      similar to the effects of gonadal steroids. However, little is known about the
      potential effects of GH on gonadal steroids and on dynamic tests of pituitary
      gonadal function in adults with GH deficiency. We evaluated the pituitary-gonadal
      axis in a 4-month double-blind, placebo-controlled GH study in 13 young males
      with childhood-onset GH deficiency of which 6 had isolated GH deficiency. GH
      treatment significantly increased serum levels of total IGF-I from 98 (68) to 323
      (126) microg/l, free IGF-I from 0.48 (0.47) to 2.24 (1.66) microg/l, IGFBP-3 from
      1,874 (1,178) to 3,520 (778) microg/l and ALS levels from 9,182 (5,524) to 16,872
      (6,278) microg/l (all p < 0.0001). We found no differences in basal testosterone
      levels in the 13 patients between the GH and placebo treatment periods (21.9
      (5.1) vs. 24.5 (8.1) nmol/l, nonsignificant). Furthermore, no effect of GH on the
      testicular response to hCG after 72 h was seen compared to placebo (36.2 (6.4)
      vs. 38.8 (10.3) nmol/l). In addition, no differences existed in basal SHBG, DHT,
      free testosterone, delta4-adion and DHEA-S levels. There were no statistically
      significant differences in maximal FSH and LH response to a GnRH challenge
      between the GH and the placebo periods (15.7 (5.3) vs. 18.0 (8.8) U/l and 47.0
      (26.4) vs. 40.4 (26.5) U/l, respectively). Furthermore, there was no effect on
      cortisol responses after ACTH between the GH and the placebo periods. However,
      significantly higher estradiol levels were seen after GH treatment (110 (50)
      pmol/l) compared to after placebo (89 (34) pmol/l, p = 0.03). Prostate-specific
      antigen levels decreased after GH treatment compared to after placebo (0.42
      (0.54) vs. 0.47 (0.48) microg/l) and this difference almost reached statistical
      significance (p = 0.059). Inhibin-B levels were significantly lower in
      hypogonadal patients substituted with androgens, but GH had no effect on inhibin
      B levels. In conclusion, GH replacement therapy in 13 GH-deficient young adult
      males resulted in significant increases in total and free IGF-I as well as in ALS
      levels in all patients, but had no significant effect on: (1) the pituitary FSH
      and LH response to GnRH; (2) basal and hCG-stimulated levels of androgens and
      SHBG; (3) basal inhibin-B levels; (4) ACTH-stimulated cortisol secretion. By
      contrast, GH administration had subtle anti-androgenic effects in terms of
      elevated elevated estradiol levels and decreased prostate-specific antigen
      levels, although both parameters remained within the normal range. Thus, at the
      level of blood chemistry the effects of GH administration do not appear to
      involve major alterations in the pituitary-gonadal axis.

PMID- 9623519
TI  - Predictive value of serum follicle-stimulating hormone levels in the
      differentiation between hypogonadotropic hypogonadism and constitutional delay of
      puberty.
AB  - OBJECTIVE: Gonadotropin secretion was evaluated to predict hypogonadotropic
      hypogonadism (HH) in 36 children suspected of having HH. METHODS: LH was measured
      for 24 h at 10-min intervals, and FSH and estradiol or testosterone at 1-hour
      intervals. Twenty boys (age 15.7, range 13.2-19.3 years) and 16 girls (age 16.1,
      range 13.0-20.6 years) were studied. RESULTS: LH pulses were detected in 9 boys
      and 5 girls. HH was confirmed in all 11 LH apulsatile boys and in 8 of 11 LH
      apulsatile girls. Random FSH values of < or =1.11 and < or =2.86 IU/l in boys and
      girls, respectively, discriminated patients with LH pulses from patients without
      (sensitivity for lack of LH pulses 97 and 100%, respectively). In boys testicular
      volume was not discriminatory. In 1 girl LH pulses were observed without
      estradiol production, suggesting LH neurosecretory dysfunction. CONCLUSIONS: Low
      FSH levels in adolescence are strongly related to a lack of LH pulses. Lack of LH
      pulses is highly suspect for HH. FSH may be a tool in the differentiation between
      HH and delayed puberty.

PMID- 9623520
TI  - Hypercalcemia due to parathyroid hormone-related protein secretion by melanoma.
AB  - About 1-2% of melanoma patients develop hypercalcemia. We report hypercalcemia
      without bone metastasis in a 46-year-old woman with advanced melanoma. The
      hypercalcemia was associated with elevated serum parathyroid hormone-related
      protein (PTHrP) levels. An even higher concentration (10 times the serum level)
      in pleural effusion caused by pleural metastases implied that the source of the
      increased circulating PTHrP was the melanoma. Immunohistochemical staining of
      paraffin sections, performed using a monoclonal antibody (9H7) against the
      peptide sequence 109-141 of human PTHrP, detected PTHrP in the cytoplasm and
      nucleoli of melanoma cells in an autopsy specimen but not in specimens from this
      patient prior to onset of hypercalcemia. Considering the evidence, it is very
      likely that PTHrP production by melanoma caused hypercalcemia in this patient.

PMID- 9623521
TI  - An association of hypothalamic hamartoma, central precocious puberty and juvenile
      granulosa cell tumour in early childhood.
AB  - A case of central precocious puberty from infancy due to a hypothalamic hamartoma
      and associated with an ovarian juvenile granulosa cell tumour is presented.
      Central precocious puberty was diagnosed by gonadotropin stimulation tests and
      LHRH agonist therapy was successful. A MR scan, but not a CT scan, demonstrated
      the hypothalamic hamartoma. The possible influence of early LH stimulation for
      the development of the granulosa cell tumour is discussed.

PMID- 9623523
TI  - On-line haemodiafiltration: state of the art.
AB  - Faced with the shortcomings of conventional dialysis on a long-term basis, as
      illustrated by the dialysis-related pathology, a need for a new strategy exists
      to improve the overall quality of treatment in end-stage renal failure (ESRF)
      patients. On-line haemodiafiltration (HDF) seems to be the best therapeutic
      option to achieve this goal at the present time. By enhancing convective
      clearances through highly permeable membranes, HDF offers the greatest solute
      fluxes both for low and higher molecular weight uraemic toxins. As for example,
      in our routinely performed HDF programme based on 3 weekly sessions lasting 3-4 h
      each, double-pool urea Kt/V achieved was 1.55+/-0.20 and beta2-microglobulin Kt/V
      was 0.91. By producing substitution fluid from fresh dialysate, the technique of
      HDF is simplified and becomes economically affordable. By improving the
      haemodynamic tolerance, HDF allows more elderly and high risk cardiovascular
      patients to be treated more safely. By using bicarbonate-buffered infusate, HDF
      facilitates the correction of acidosis. Both by using ultrapure bicarbonate
      dialysate and down-regulating the membrane reactivity via a 'protein cake', HDF
      introduces the first step for a full haemocompatibility concept. Finally, by
      giving access to virtually unlimited amounts of sterile and non-pyrogenic fluid,
      HDF should introduce new therapeutic options such as a totally automated and feed
      back-controlled machine. Today's on-line HDF is already a step forward to enhance
      the overall efficacy of renal replacement therapy and to improve the global care
      of ESRF patients.

PMID- 9623522
TI  - Three cases of malignant pheochromocytoma treated with cyclophosphamide,
      vincristine, and dacarbazine combination chemotherapy and alpha-methyl-p-tyrosine
      to control hypercatecholaminemia.
AB  - We describe 3 cases of malignant pheochromocytoma with multiple metastases which
      were treated with cyclophosphamide, vincristine and dacarbazine (CVD) combination
      chemotherapy and alpha-methyl-p-tyrosine. Case 1 was operated on first but
      hypercatecholaminemia could not be completely controlled. Cases 2 and 3 received
      chemotherapy, CVD combination chemotherapy and/ or alpha-methyltyrosine and good
      control of hypercatecholaminemia was attained. In all cases it was possible to
      control hypercatecholaminemia during most of the time they were administered a
      methyltyrosine despite the presence of tumors. None of the patients suffered
      hypertension crises. In our patients treatment with CVD plus a-methyl-p-tyrosine
      proved to be safe and ameliorated the clinical course.

PMID- 9623524
TI  - Water quality for on-line haemodiafiltration.
AB  - The term 'ultrapure water' is a common way to define water used for on-line
      treatments: it refers to the absence of chemical, organic and microbiological
      contamination. To be more accurate in definition, every known and potential
      contaminant has to be fixed at its limit value. AAMI recommendations and various
      Pharmacopoeias have set limits for dialysate based on traditional dialysis
      treatments, but on-line treatments should also be regulated by guidelines for
      infusion solutions. Modern water treatment technology allows us to obtain a
      proper chemical quality both for dialysate and infusion solutions in on-line
      dialysis. Technology alone, however, cannot guarantee adequate microbiological
      quality if water treatment is not linked to the appropriate maintenance,
      monitoring, cleaning and sanitizing procedures. On-line dialysis treatments, as
      well as high-flux dialysis, use the monitor as an on-site pharmaceutical factory
      where sterilization by filtration forces nephrologists to look for procedures to
      keep sterile water sterile.

PMID- 9623525
TI  - Assessment of the quality of dialysate.

PMID- 9623526
TI  - Regulatory issues for on-line haemodiafiltration.

PMID- 9623527
TI  - Trace elements and micropollutant anions in the dialysis and reinfusion fluid
      prepared on-line for haemodiafiltration.
AB  - Exposure to the trace elements and micropollutions of tap water may be very
      considerable in dialysis patients. As few data on trace elements in reinfusion
      and dialysis fluid for haemodiafiltration (HDF) have been reported, we studied
      nine trace elements (microg/l; Al, As, Cd, Cr, Cu, Hg, Pb, Se, Zn) and five
      anions (mg/l; F-, NO2-, NO3-, PO4(3-), SO4(2-)) in tap water, in water after two
      passages of reverse osmosis (2RO), in dialysate and in on-line prepared
      reinfusate. NO3- and SO4(2-) were somewhat elevated in our tap water (22.2+/-7.6
      and 21.8+/-11.3 mg/l) but decreased (P<0.001) after 2RO (1.4+/-1.5 and 0.9+/-1.1
      mg/l); the other anions, which were at a very low level, remained unchanged. All
      trace elements decreased, with statistical significance only for Al, Cr and Zn
      from 14.9+/-19.9, 2.6+/-0.6 and 35.1+/-41.1 microg/ to 3.2+/-2.1, 0.2+/-0.2 and
      3.5+/-4.8 microg/l, respectively. Due to impurities in concentrate salts for Al
      (5.4+/-3.1), Cr (0.5+/-0.4) and SO4(2-) (2.4+/-1.8), greater concentrations were
      found in dialysate and reinfusate than in tap water after 2RO (P<0.03). For all
      measurements, trace elements and anions were at acceptable levels according to
      international standards. Simultaneous determinations of trace elements at inflow
      (Din) and outflow (Dout) of the dialysate as well as in plasma or in whole blood
      at the beginning of on-line HDF documented Dout/Din>1 for Al, Cu and Zn and a
      positive gradient between the concentration in blood and dialysate inlet. In
      conclusion, our dialysate and reinfusate can be considered safe regarding trace
      elements and micropollution: two passages through reverse osmosis reduces the
      concentrations of trace elements and anions. The impurities of concentrates are
      acceptable. Accumulation or depletion of trace elements should be evaluated after
      longitudinal studies of plasma concentrations.

PMID- 9623528
TI  - Plasma or whole blood concentrations of trace elements in patients treated by
      haemodiafiltration with on-line prepared substitution fluid.
AB  - Large membrane pores and large quantities of reinfusion fluids can influence the
      dialytic balance of trace elements in haemodiafiltration (HDF). As there are no
      studies in HDF with on-line produced reinfusate, we studied plasma or whole blood
      (*) concentrations of trace elements (Al, Cd*, Cr* and Se: microg/l; Cu, Pb* and
      Zn*: microg/dl) of 24 on-line HDF, 20 haemodialysis (HD) patients and 66 490
      normal subjects (N). The concentrations of Al (11.7+/-9.5), Cd (0.73+/-0.59) and
      Cr (6.5+/-6.9) were significantly greater in on-line HDF patients than in normal
      subjects (6+/-0.4; 0.6+/-0.2; 0.5+/-0.02), but similar to those of HD patients.
      In on-line HDF patients, Cu (85.3+/-17.7), Pb (8+/-4.6), Se (68+/-27) and Zn
      (546+/-103) concentrations were less than in normal subjects (108+/-3.4; 11+/
      0.8; 95+/-1.8; 673+/-23), and those of Cu and Zn were also less than in HD
      patients (99.5+/-16.8; 670+/-65). At the end of an on-line HDF treatment (42-69
      studies), there was a significant increase in Al (from 12.8+/-9.1 to 15.4+/-8.3),
      Cr (from 7.2+/-6.4 to 9.5+/-7), Cu (from 97.3+/-21.5 to 109.4+/-27.2) and Zn
      (from 577+/-108 to 619+/-117). A longitudinal study (n = 16-18) for 12-30 months
      documented stable concentrations of Al, Cd, Cr, Se and Zn and a significant
      increase of Cu and Pb to normal concentrations. In conclusion, our on-line HDF
      patients have elevated Al, Cd, Cr and decreased Cu, Pb, Se, Zn concentrations in
      plasma or whole blood determinations. Cu and Pb normalize with time; the other
      trace elements remain stable as documented by numerous determinations. As the
      values for on-line HDF patients are similar to those of HD patients, the level of
      accumulation or depletion of trace elements in on-line HDF can be considered as
      safe as in HD; the increase in Al, Cd, Cu and Zn at the end of treatment may be
      an expression of the increase of those trace elements linked to proteins.

PMID- 9623529
TI  - Clinical perspectives of on-line haemodiafiltration.

PMID- 9623530
TI  - Leptin--a new hormone of definite interest for the nephrologist.

PMID- 9623531
TI  - T lymphocyte-derived cytokines in experimental glomerulonephritis: testing the
      Th1/Th2 hypothesis.

PMID- 9623532
TI  - Diabetic kidney disease: the role of growth factors.

PMID- 9623533
TI  - Are all patients with idiopathic focal segmental glomerulosclerosis (FSGS)
      created equal?

PMID- 9623534
TI  - Controversial association of left ventricular hypertrophy and the ACE I/D
      polymorphism--is the mist clearing up?

PMID- 9623535
TI  - Cardiac disease in the diabetic dialysis patient.

PMID- 9623536
TI  - Why so much disparity of PD in Europe?

PMID- 9623537
TI  - Major histocompatibility complex-associated odours.

PMID- 9623538
TI  - Non-steroidal anti-inflammatory agents in patients with a renal transplant.

PMID- 9623539
TI  - Perchloroethylene-induced nephrotoxicity in dry-cleaning workers: is there a role
      for free radicals?

PMID- 9623540
TI  - Diabetic nephropathy and the insertion/deletion polymorphism of the angiotensin
      converting enzyme gene.

PMID- 9623541
TI  - Molecular mechanisms of angiotensin II in the kidney: emerging role in the
      progression of renal disease: beyond haemodynamics.

PMID- 9623542
TI  - Epidemiology of end-stage renal failure in Reunion Island (results from the
      registry of the Indian Ocean Society of Nephrology).
AB  - BACKGROUND: End-stage renal disease (ESRD) on long-term dialysis is a substantial
      problem in Reunion because of the high incidence and prevalence of this disease
      due to non-insulin-dependent diabetes mellitus (NIDDM) and systemic arterial
      hypertension. SUBJECTS AND METHODS: In 1996 the renal study group of the Indian
      Ocean Society of Nephrology established a regional registry of end-stage renal
      failure (ESRD) on long-term dialysis. The present report summarizes data obtained
      from this registry. RESULTS: In 1996, there were 125 patients who were initiated
      on long-term dialysis, 657 patients on dialysis with a mean age 52 +/- 17 years,
      and 110 patients with a functioning kidney graft. The incidence rate of ESRD was
      188 per million population (p.m.p.) and the prevalence rate of this pathology was
      1155 p.m.p. The sex ratio (F/M) was 1.4/1. The two most common causes of ESRD
      were NIDDM in 33.6% and systemic arterial hypertension in 27.5%. The mean Kt/V
      value was 1.47 +/- 0.23 and the mortality rate was 8.1% per year. CONCLUSION: The
      results demonstrate high incidence and prevalence rates of ESRD mainly as a
      result of NIDDM and systemic arterial hypertension.

PMID- 9623543
TI  - Emerging ties between the ERA-EDTA and Latin American nephrology.

PMID- 9623544
TI  - Dialysis withdrawal--a case report.

PMID- 9623545
TI  - Issues surrounding the withdrawal of dialysis treatment.

PMID- 9623546
TI  - Dialysis treatment withdrawal--legal aspects (UK).

PMID- 9623547
TI  - Support after discontinuation of dialysis--medical and ethical considerations.

PMID- 9623548
TI  - Apoptosis and necrosis during ischaemia in renal tubular cells (LLC-PK1 and
      MDCK).
AB  - BACKGROUND: Ischaemia is the most frequent cause of acute renal failure. It has
      been previously demonstrated that ischaemia is connected with signs of necrosis
      and apoptosis. Apoptosis is an energy-dependent process. During ischaemia
      intercellular energy levels decline rapidly. Therefore, the goal of the
      investigation was to reveal the time dependency of cell death mechanisms during
      ischaemia leading to irreversibility of tissue damage. METHODS AND RESULTS: A
      model of renal ischaemia induced by ATP depletion was used in LLC-PK1 and MDCK
      cells. Cell proliferation, determined by 3H-thymidine and BrdU incorporation and
      by the Ki67-labelling index was affected already after 1-2 h of ATP depletion in
      both cell lines. Cell viability and membrane leakage, estimated by trypan blue
      and propidium iodide exclusion and LDH release, was profoundly increased after 8
      16 h. Evaluation of mechanisms of necrotic or apoptotic cell death was calculated
      from fraction of cells with pyknotic nuclei, investigation of DNA fragmentation
      and, by translocation of phosphatidylserine (PS) from the inner membrane face to
      the surface. In both cell lines increased numbers of cells with condensed nuclei
      was not a major sign of apoptosis. Only in MDCK cells were the numbers of cells
      with condensed nuclei significantly increased after 1 h compared to controls. As
      a hallmark of apoptosis, ATP depletion resulted in intranucleosomal DNA
      fragmentation after 1 h. After 8-16 h this pattern changed to a smear pattern, as
      a sign for necrosis. PS staining was detectable at the cell surface after 1 h.
      CONCLUSIONS: Ischaemia is associated with a rapid loss of proliferation and signs
      of apoptosis at early stages in a small proportion of cells. Most cells undergo
      the necrotic pathway of cell death after prolonged ATP depletion (8 h). There was
      no difference in behaviour comparing proximal (LLC-PK1) with more distal (MDCK)
      cell culture models. These results may help to explain the findings that
      apoptosis and necrosis have both been described after renal ischaemia.

PMID- 9623550
TI  - GFR measurement with iohexol and 51Cr-EDTA. A comparison of the two favoured GFR
      markers in Europe.
AB  - BACKGROUND: The aim of the present study was to compare the most commonly used
      GFR markers for clearance measurements, 51Cr-EDTA and iohexol, using two
      different methods for iohexol analysis, HPLC and X-ray fluorescence, referring
      both to the multiple-sample and single-sample calculations, using 51Cr-EDTA as
      the reference method. METHODS: Forty-nine patients with an estimated GFR >40
      ml/min were included. 51Cr-EDTA and iohexol were injected simultaneously and
      blood samples were taken 150, 195 and 240 min after injection of the respective
      marker. RESULTS: The multiple-point clearances, determined from HPLC and X-ray
      fluorescence, compared to 51Cr-EDTA correlated highly (r=0.92 and 0.95
      respectively). The results from single-point clearance comparison, iohexol
      measured by HPLC vs 51Cr-EDTA, yielded a correlation of r=0.91, while single
      point clearance from iohexol, analysed by X-ray fluorescence, obtained a
      correlation of 0.93 and an intercept statistically different from origo.
      CONCLUSIONS: Iohexol and 51Cr-EDTA are comparable as GFR markers for multiple
      point clearance measurements. The single-sample method for GFR >40 ml/min can be
      used with a high accuracy. The precision and accuracy of X-ray fluorescence
      analysis of low concentrations of iohexol were less than those of HPLC. Care
      should therefore be taken when using X-ray fluorescence that the injected dose of
      iohexol should result in a plasma concentration level of iodine of at least 0.06
      mg/ml at the time of blood sampling.

PMID- 9623549
TI  - Enhanced glomerular expression of caldesmon in IgA nephropathy and its
      suppression by glucocorticoid-heparin therapy.
AB  - BACKGROUND: Activation and consequent phenotypic modulation of mesangial cells is
      considered to play a crucial role in the process of glomerular disease
      progression. Caldesmon, a calmodulin and actin-binding protein, is a molecular
      marker of the phenotypic change in smooth-muscle cells. SUBJECTS AND METHODS: We
      studied whether the expression of caldesmon in mesangial cells was enhanced in
      the process of IgA nephropathy and whether it would be a marker of mesangial
      activation indicating prognostic significance in specific disease states. We
      performed immunohistochemical staining with anticaldesmon and alpha-smooth-muscle
      actin (alpha-SMA) antibodies in 32 biopsy specimens from IgA nephropathy patients
      and analysed them quantitatively with a computer-aided manipulator. RESULTS: The
      glomerular expression of caldesmon was enhanced in IgA nephropathy patients. We
      compared caldesmon expression with composite histological scores (cell score and
      matrix score), clinical parameters and expressions of alpha-SMA. There was a
      statistically significant correlation between the caldesmon score and the
      histological scores (cell score and matrix score, P<0.0001, P<0.01 respectively).
      Patients showing a high intensity of caldesmon expression (defined as caldesmon
      score > or = 35; H-group) had significantly higher urinary protein excretion than
      those showing a low intensity of caldesmon expression (defined as caldesmon score
      < 35; L-group) (1.2 +/- 1.2 g/24 h vs 0.41 +/- 0.53 g/24 h, P<0.05). Caldesmon
      and alpha-SMA expression had a statistically significant correlation (P<0.000).
      Next, 13 patients were treated with glucocorticoid-heparin for 4-8 weeks and re
      biopsies were performed. After the therapy, the caldesmon and alpha-SMA scores
      were significantly lower than those before the therapy (P<0.01). DISCUSSION:
      These results suggest that the expression of caldesmon in glomeruli is associated
      with the progression of IgA nephropathy, and that glucocorticoid heparin therapy
      may reverse the phenotype of mesangial cells during the disease process of
      glomerulonephritis.

PMID- 9623551
TI  - Increased atherogenicity of low-density lipoprotein in heavy proteinuria.
AB  - BACKGROUND: Heavy proteinuria is associated with marked abnormalities of
      lipoprotein metabolism and increased risk of atherogenesis. It is possible that
      qualitative as well as quantitative changes occur in lipoproteins to contribute
      to increased cardiovascular risk; for example, it is known that LDL exhibits
      heterogeneity, with small, dense LDL III particles being more atherogenic.
      METHODS: We investigated LDL subfractions (measured by density gradient
      ultracentrifugation), VLDL subfractions, and post-heparin lipases in 12 patients
      with primary glomerular disease and 24-h albuminuria >2.5 g. These were compared
      to 23 age- and sex-matched controls. RESULTS: Total LDL concentrations were
      similar in proteinuric patients and controls; however, there was a shift in
      subfraction distribution. The larger LDL I and LDL II particles were lower in the
      proteinuric group (29 +/- 24 vs 62 +/- 26 mg/dl P=0.011 and 121 +/- 80 vs 197 +/-
      74 mg/dl P=0.028), whereas the concentration of atherogenic LDL III (small dense)
      was higher (135 +/- 64 vs 75 +/- 71 mg/dl P=0.0016). The concentration of total
      VLDL and both its subfractions were increased in the patients with proteinuria.
      Post-heparin hepatic and lipoprotein lipase levels were similar to normal.
      CONCLUSIONS: These findings suggest that the atherogenicity of LDL is increased
      in patients with heavy proteinuria because of the redistribution towards smaller
      denser particles. Since small, dense LDL has a lower affinity for the LDL
      receptor, the altered nature of the lipoprotein in proteinuria may decrease its
      clearance by the receptor-mediated pathway and contribute to the reduced
      clearance of LDL observed in this population. This may contribute to progression
      of renal failure or the accelerated vascular disease found in patients with heavy
      proteinuria.

PMID- 9623552
TI  - Pharmacokinetics of pantoprazole in patients with end-stage renal failure.
AB  - BACKGROUND: Pantoprazole is a selective inhibitor of the gastric H+/K+-ATPase
      with a low potential to interact with the cytochrome P450 enzyme system. Since
      pantoprazole is metabolized in the liver to metabolites which are mainly cleared
      by the renal route, it was the aim of this study to investigate its
      pharmacokinetics in patients with end-stage renal failure undergoing regular
      haemodialysis. METHODS: Eight patients with end-stage renal failure (creatinine
      clearance < 5 ml/min, age 45-65 years) on regular haemodialysis (duration of
      haemodialysis 4-5 h, cuprophan-dialyser Hemoflow E3, surface 1.3 m2) were given
      single i.v. doses of 40 mg pantoprazole one day before haemodialysis (A) and on a
      haemodialysis day immediately before the start of the haemodialysis (B).
      Concentrations of pantoprazole and metabolite M2 were determined in plasma and
      urine over 24 h and in timed samples of the dialysis fluid by HPLC. The protein
      binding was determined using equilibrium dialysis. RESULTS: The pharmacokinetic
      characteristics of pantoprazole AUC, t(1/2), CL and V(d area) (geometric means)
      were 2.4 mgxh/l, 0.63 h, 0.227 l/h/kg and 0.206 l/kg on day A (without dialysis)
      and 2.3 mgxh/l, 0.8 h, 0.237 l/h/kg and 0.273 l/kg on day B (with dialysis),
      respectively. The protein binding was 96%. Pantoprazole was found in small
      amounts in the dialysis fluid (max. 2.1% of the dose) but not in the urine.
      Pantoprazole was well tolerated. In particular, there were no clinically relevant
      changes in blood count, electrolytes or liver enzymes. CONCLUSIONS: Haemodialysis
      has no influence on the pharmacokinetic characteristics of pantoprazole. Thus,
      pantoprazole is not dialysed to any relevant degree, and therefore no dose
      adjustment is required for patients with end-stage renal failure undergoing
      regular haemodialysis treatment.

PMID- 9623553
TI  - Desferrioxamine improves burst-forming unit-erythroid (BFU-E) proliferation in
      haemodialysis patients.
AB  - BACKGROUND: In chronic renal failure, desferrioxamine (DFO) may improve
      erythropoiesis independent from its aluminium (Al) chelating effect. The
      mechanism of this action is still unknown. METHODS: To verify whether DFO
      influences proliferation of erythropoietic precursors, we studied 10 patients on
      chronic haemodialysis, free from malignancies or other haematological diseases,
      iron deficiency, bone marrow fibrosis, and Al toxicity. Al accumulation was
      excluded by the DFO test. Peripheral blood samples were drawn for basal burst
      forming unit erythroid (BFU E) assay. Mononuclear cells were isolated by density
      gradient centrifugation with Ficoll Hypaque, and incubated for 15 days with three
      different experimental conditions: (a) low-dose recombinant human erythropoietin
      (rHuEpo) (3 U/ml); (b) high dose rHuEpo, (30 U/ml); (c) both DFO (167 microg/ml)
      and rHuEpo (3 U/ml). We determined TIBC, transferrin, ferritin, reticulocytes,
      hypochromic erythrocytes, soluble transferrin receptor (sTR), haemoglobin (Hb),
      and haematocrit (Hct) at baseline and then every 14 days. Patients received 5
      mg/kg DFO infused during the last hour of each dialysis session for 6 weeks; six
      patients remained in the study for an additional 6 more weeks. BFU E assays were
      set up after 6 and 12 weeks of DFO therapy. RESULTS: At baseline DFO had small
      effect on BFU E proliferation (33.9+/-25 vs 30.4+/-25.9) and high-dose rHuEpo had
      a significant effect (45.15+/-27 vs 30.4+/-25.9, P<0.01). After 6 weeks of DFO
      therapy a significant increase in BFU E proliferation was observed in all culture
      conditions (78.25+/-32 vs 30.45+/-25.9 standard culture, P<0.01; 110.9+/-30 vs
      45.15+/-27 high dose rHuEpo, P<0.01; 98.75+/-32 vs 45.15+/-27 DFO culture,
      P<0.01). Moreover, the increase in BFU E proliferation was significant greater
      with DFO culture than standard culture (P<0.01). The same trend was found at the
      third BFU E assay, performed in only six patients, when all culture conditions
      showed a further increase of erythroid precursor proliferation. However, the DFO
      culture was not significantly greater than the standard culture, while the high
      dose rHuEpo was significantly greater than the DFO culture. Patients in group I
      (n=10), had a significant increase in reticulocytes (1.5+/-0.6 vs 1.72+/-0.3,
      P<0.01) and of hypochromic erythrocytes (HE) (5.6+/-5.1 vs 14.4+/-12.7, P<0.01),
      while sTR, Epo, Hb, and Hct were only minimally increased. Ferritin decreased
      significantly (448+/-224 vs 196+/-215, P<0.01) and TIBC and transferrin were
      unchanged. CONCLUSIONS: Thus DFO increases erythroid activity by BFU E
      proliferation and increases reticulocytes in haemodialysis patients. Such an
      effect may be related to increased iron utilization. DFO may be a useful tool for
      anaemic patients with good iron stores and without Al overload.

PMID- 9623554
TI  - Influence of long-term recombinant human erythropoietin (rHuEpo) therapy on
      plasma leptin and neuropeptide Y concentration in haemodialysed uraemic patients.
AB  - BACKGROUND: In patients with chronic renal failure, rHuEpo therapy ameliorates
      anaemia and improves wellbeing, exercise tolerance, and appetite. Both leptin and
      neuropeptide Y play an important role in regulation of appetite and energy
      balance in humans. METHODS: The present study aimed to assess the influence of 12
      months rHuEpo therapy on plasma leptin and neuropeptide Y concentrations in 15
      haemodialysed patients (HDP) (6F, 9M; mean age 40.8+/-2.9 years; mean BMI 23.6+/
      1.1 kg/m2; mean duration of HD 3.3+/-0.6 months) (Epo group). A second group (No
      Epo group) consisted of 17 HDP (9F, 8M; mean age 44+/-3.2 years; mean BMI 24.3+/
      1.0 kg/m2; mean duration of HD 2.5+/-0.4 months) not treated with rHuEpo for 12
      months. Basal plasma leptin and neuropeptide Y concentrations were estimated by
      RIA at the beginning and after 3, 6, 9 and 12 months of rHuEpo therapy (Epo
      group) or clinical observation (No-Epo group). The control group consisted of 30
      healthy subjects (15 females, 15 males, mean age=38.2+/-1.7 years, mean BMI
      24.5+/-0.7 kg/m2). RESULTS: Baseline plasma leptin concentrations in HDP were
      higher, although statistically not significant than leptinaemia in healthy
      subjects. After 3, 6, and 12 months of rHuEpo therapy plasma leptin
      concentrations were significantly lower than at the beginning of the study.
      Baseline plasma neuropeptide Y concentrations in HDP did not differ significantly
      from controls. After 3 and 6 months of the study period plasma neuropeptide Y
      concentrations increased significantly in patients of both the Epo and No-Epo
      group. This increase was, however, significantly higher in rHuEpo-treated than in
      untreated patients. CONCLUSIONS: (1) rHuEpo treatment in haemodialysed patients
      with chronic renal failure is followed by a significant decline of leptinaemia
      and disappearance of the physiological positive BMI/leptinaemia relationship. (2)
      Suppression of leptinaemia induced by rHuEpo may be of clinical relevance in
      haemodialysed patients with chronic renal failure.

PMID- 9623555
TI  - High dose enalapril impairs the response to erythropoietin treatment in
      haemodialysis patients.
AB  - BACKGROUND: The resistance to recombinant human erythropoietin (rHuEpo) therapy
      in haemodialysis (HD) patients has multifactorial aetiologies: erythropoietin
      insufficiency, dialysis insufficiency, iron deficiency, and secondary
      hyperparathyroidism. Angiotensin-converting enzyme (ACE) inhibitors induce
      anaemia in patients with essential hypertension, congestive heart failure,
      chronic renal insufficiency, and renal transplants. Data exist suggesting that
      ACE inhibitors impair erythropoiesis in HD patients. Therefore the aim of this
      study was to investigate the impact of enalapril on rHuEpo requirement. METHODS:
      In the present prospective non-randomized study of 12 months, we compared the
      effects of enalapril and nifedipine on rHuEpo requirement in 40 hypertensive
      patients receiving rHuEpo for more than 6 months on maintenance haemodialysis.
      Twenty normotensive rHuEpo-dependent patients served as a control group. All
      patients with severe hyperparathyroidism or iron deficiency were excluded.
      RESULTS: The mean (+/- SD) haemoglobin concentration was > 10 g/dl in all groups.
      The mean weekly rHuEpo dose increased in the enalapril group (P<0.0001 vs before)
      and remained constant in the nifedipine and control groups (P=NS vs before).
      Statistically, there was no differences with regard to iPTH levels, dialysis
      parameters, iron status, and underlying renal diseases among all groups.
      CONCLUSION: High-dose enalapril increases rHuEpo requirement and should be
      reserved for dialysis patients with hypertension uncontrollable with other
      antihypertensive medications or dialysis patients with cardiac failure.

PMID- 9623556
TI  - A 3-year follow-up of HCV-RNA viraemia in haemodialysis patients.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection in a population of haemodialysed
      patients was studied over a 3-year follow-up period in order to evaluate the
      changes in viral RNA, diversity of genotypes, and serological response to
      synthetic HCV peptides. METHODS: Twenty-eight (32.9%) patients with anti-HCV
      antibodies from a total of 85 patients assigned to a haemodialysis unit were
      studied. The serological response to immunopeptides was evaluated by
      immunoblotting, viral RNA in serum was detected using the polymerase chain
      reaction (RT-PCR), and genotyping was carried out by hybridization with probes
      fixed to nitrocellulose paper. RESULTS: Of the 28 haemodialysis patients who had
      anti-HCV antibodies, three (10.7%) were always RNA negative, six (21.4%) were
      always RNA positive, and 19 (67.8%) were variable RNA. There was an incomplete
      antibody response to non structural antigens in non-viraemic patients. Genotype
      was determined in 23 patients, and the other two could not be genotyped. The most
      common genotype was 1b (69.4%), followed by 1a (17.4%), and 2a, 3a, and 4a (each
      4.4%). CONCLUSIONS: Haemodialysis patients, when followed up for a long time,
      frequently show an intermittent HCV viraemia state, suggesting that HCV cannot be
      evaluated adequately by isolated RNA determinations.

PMID- 9623557
TI  - The femoral artery-femoral vein polytetrafluoroethylene graft: a 14-year
      retrospective study.
AB  - BACKGROUND: The use of the femoral vessels for permanent haemodialysis access has
      been neglected during the last two decades. Since 1981 femoral artery-vein loop
      polytetrafluoroethylene grafts have been constructed in our chronic haemodialysis
      patients. This study examines results obtained in patients with this particular
      graft over the last 14 years. METHODS: This clinical study is retrospective in
      nature. Overall 35 patients, with 37 femoral grafts, are included. Inclusion and
      exclusion criteria for this type of graft are given and the surgical procedure
      detailed. RESULTS: Seven patients had femoral grafts used as primary dialysis
      access. Twenty-eight patients had femoral grafts used after multiple access
      failures. There was no perioperative mortality. Immediate thrombotic non-function
      of the graft occurred in three patients. In the long term no patient death was
      related to the femoral grafts. Twenty-seven (73%) grafts had no long-term
      complications. The leading cause for graft 'loss' was patient death; in the first
      year 10 grafts were lost, eight because of patient death. All eight patients died
      with functioning grafts. Median graft survival was 21 months in all patients and
      28 months in non-diabetic patients. Twenty-seven (73%) grafts were patent at the
      end of the first year, 33% of grafts were still patent after 5 years. Worsening
      claudication occurred in four patients; one diabetic required foot amputation.
      Four patients had late graft thrombosis; only two patients had bacteraemia
      originating from the femoral graft. Urea reduction ratio greater than 60% was
      measured in 87.5% of patients. CONCLUSION: The femoral artery vein graft is a
      good primary and secondary haemodialysis access. Both infection and thrombosis
      rates are low and graft survival is comparable, if not superior to, that of upper
      limb grafts. The graft is easy to cannulate, can be used early, is easily
      protected, and is cosmetically acceptable.

PMID- 9623558
TI  - Laparoscopic nephrectomy: comparison of dialysis and non-dialysis patients.
AB  - BACKGROUND: Laparoscopy is believed to result in possible clinical benefits for
      the patient. We report our experience with renal laparoscopy in dialysis patients
      and compare the results with those from non-dialysis patients. METHODS: Between
      December 1994 and April 1997, 19 dialysis patients underwent laparoscopic
      nephrectomy or nephroureterectomy at our hospital. The group consisted of 11
      female and eight male patients (mean age 45 years). In nine patients the
      indication for nephrectomy was chronic pyelonephritis. Nephroureterectomy for
      vesicoureteral reflux with recurrent episodes of pyelonephritis or analgesic
      nephropathy for exclusion of transitional cell carcinoma of the upper urinary
      tract was considered in nine other patients. Laparoscopic bilateral nephrectomy
      for drug-resistant hypertension was performed in one patient. In comparison, a
      consecutive group of non-dialysis patients who had undergone renal laparoscopy
      was reviewed. RESULTS: In the dialysis group, one patient had to be converted to
      open nephrectomy due to bleeding. Six dialysis patients required blood
      transfusions compared with none in the non-dialysis group. There were four
      complications in the dialysis group and two in the non-dialysis group. Both
      groups had comparable results for operative times, analgesic consumption,
      postoperative start of oral intake and mobilization, and duration of
      hospitalization and convalescence. CONCLUSIONS: Laparoscopic nephrectomy in
      dialysis patients has acceptable results. The higher transfusion rate is probably
      due to a lower preoperative haemoglobin and is not aggravated by possible affects
      of the clotting system in patients with chronic uraemia.

PMID- 9623559
TI  - Patients surviving more than 10 years on haemodialysis. The natural history of
      the complications of treatment.
AB  - BACKGROUND: The purpose of this survey was to describe the natural history of
      complications in 52 long-surviving haemodialysis patients to obtain a clearer
      picture of the impact these patients have on the dialysis population. This is
      important as they are often no longer suitable for transplantation and therefore
      are destined to remain on dialysis for the rest of their lives. METHODS: The
      patients who survived for more than 10 years on haemodialysis alone were studied.
      Information was obtained from patients' records and from the renal unit computer.
      RESULTS: Mean age at start of dialysis was 43 years and mean duration of HD 14.5
      years. Renal failure was most commonly due to polycystic kidney disease or
      glomerulonephritis. Sixty-two per cent of patients developed cardiovascular
      disease, 78% complained of joint pains, 72% had a parathyroidectomy, and 50%
      developed carpal-tunnel syndrome. Two hundred and forty-five episodes of
      infection were recorded, 41% related to vascular access acquired in hospital or
      on immunosuppression. Only three infections occurred which could be described as
      opportunistic. Twelve patients were hepatitis C positive. In the 37 patients who
      have died, cardiovascular disease was the most common cause of death. Compared to
      other patients who started on dialysis before 1986 but who had a successful
      transplant the survival of patients on haemodialysis is much worse. CONCLUSION:
      Long-term survival on renal replacement therapy is dependent on successful
      transplantation. Complications, morbidity, and mortality are high after 10 years
      of dialysis.

PMID- 9623561
TI  - Increased peritoneal permeability is associated with decreased fluid and small
      solute removal and higher mortality in CAPD patients.
AB  - BACKGROUND: Recent studies suggest that increased peritoneal membrane
      permeability is associated with higher morbidity and mortality in peritoneal
      dialysis patients. It is not known, however, whether the difference in clinical
      outcome among different peritoneal transport groups is due to differences in
      peritoneal fluid and solute removal. In the present study, we compared the
      peritoneal fluid and solute transport and clinical outcome in CAPD patients with
      high (H), high-average (H-A), low-average (L-A) and low (L) peritoneal transport
      patterns. DESIGN: A 6-h dwell study was performed in 46 patients with frequent
      dialysate and plasma samples using 2 l of 3.86% glucose dialysate with 131I
      albumin as an intraperitoneal volume marker. The patients were divided into four
      transport groups according to their D/P of creatinine at 240 min. RESULTS: The
      results showed that high transporters had significantly lower peritoneal fluid
      and small-solute removal but high glucose absorption and high protein loss during
      a 6-h exchange. The serum albumin was lower and blood pressure and triglycerides
      were higher in high transporters compared with the other groups. Two-year patient
      survival from the start of CAPD treatment was significantly lower for high
      transporters (64, 85, 90 and 100% for H, H-A, L-A and L respectively, P < 0.01).
      The 1-year patient survival from the dwell study was also significantly lower in
      high transporters (16, 63, 90 and 100% for each group, P<0.01). CONCLUSION: Our
      results suggest that high transporters remove less fluid and small solutes and
      have higher protein loss and increased glucose absorption. These alterations may
      contribute to fluid overload, malnutrition and lipid abnormalities that perhaps
      contribute to the increased mortality among the high transporters.

PMID- 9623560
TI  - Safety and efficacy of pulse and daily calcitriol in patients on CAPD: a
      randomized trial.
AB  - BACKGROUND: Calcitriol therapy is the mainstay of therapy for the treatment of
      secondary hyperparathyroidism. Oral administration of calcitriol is necessary in
      CAPD patients, but no studies have directly compared different routes of
      administration in this patient population. METHODS: To determine if the peak
      serum calcitriol level (pulse therapy) is more important than the total delivered
      dose, we randomized CAPD patients with mild to moderate secondary
      hyperparathyroidism to receive either pulse (3.0 microg twice a week, n = 10) or
      daily (0.75 microg a day, n = 8) oral calcitriol in comparable weekly doses. The
      main comparison was the rate of decline of serum intact parathyroid hormone (PTH)
      levels to reach the desired end-point of 100 pg/ml. The patients were dialysed
      with low-calcium dialysate and received only calcium-containing phosphate
      binders. RESULTS: Pharmacokinetic analysis after a single dose of 3.0 microg
      (pulse) vs 0.75 microg (daily) revealed 1,25(OH)2-vitamin D levels to be higher
      in the pulse group at 3 and 6 h, but equivalent by 12 h. The area under the curve
      for 1 week of daily and 1 week of pulse therapy was equal. The patients in the 2
      arms had equivalent basal serum levels of PTH (pulse = 562 +/- 291 vs daily = 454
      +/- 113 pg/ml), calcium (pulse = 2.32 +/- 0.20 vs daily = 2.32 +/- 0.12 mmol/l)
      and phosphorus (pulse = 1.32 +/- 0.52 vs daily = 1.35 +/- 0.26 mmol/l). The time
      required for the PTH to decrease to 100 pg/ml and the rate of decline in PTH were
      similar (time: pulse = 14.2 +/- 6.8 weeks, daily = 12.2 +/- 7 weeks; rate: pulse
      = 7.4 +/- 4.2 vs daily = 8.4 +/- 4.2% PTH/week; P = NS). The serum calcium
      increased similarly in both groups. Hypercalcaemia (> 2.9 mmol/l) was rare (pulse
      = 3, daily = 2 episodes). CONCLUSIONS: This study demonstrates that pulse and
      daily calcitriol are similarly effective and safe for the treatment of mild to
      moderate secondary hyperparathyroidism in CAPD patients despite higher peak
      levels of 1,25(OH)2-vitamin D with pulse therapy.

PMID- 9623562
TI  - Low bone mass and high incidence of fractures after successful simultaneous
      pancreas-kidney transplantation.
AB  - BACKGROUND: Simultaneous pancreas-kidney transplantation successfully restores
      normoglycaemia and corrects uraemia in insulin-dependent diabetes mellitus
      patients with end-stage renal failure due to diabetic nephropathy. Low bone
      turnover and cortical osteopenia are often associated with the diabetic state and
      corticosteroid-induced bone loss, predominantly trabecular, is expected post
      transplantation. Little is known, however, about the resultant long-term effects
      of successful simultaneous pancreas-kidney transplantation on bone mass and
      consequent fracture rate. METHODS: We studied bone and mineral metabolism, bone
      densitometry (using dual X-ray absorptiometry), and fracture prevalence in a
      cross-sectional design in 31 IDDM patients at least 12 months (mean 40+/-23
      months) after successful simultaneous pancreas-kidney transplantation. RESULTS:
      All patients were insulin-independent and mean creatinine clearance was 64 +/- 21
      ml/min. Secondary hyperparathyroidism, probably multifactorial, was found in 55%
      of the patients. Increased bone turnover as suggested by elevated osteocalcin
      concentrations was present in 45% of the patients. Twenty-three per cent of
      patients had a significant decrease in bone mass (T score < -2.5 SD) at the
      predominantly trabecular lumbar spine sites. In contrast, 58% demonstrated a
      similarly low bone mass at the femoral neck, where cortical bone is prevalent.
      Forty-five per cent of patients had documented vertebral (mostly asymptomatic)
      and non-vertebral fractures. CONCLUSION: Our findings suggest that low bone mass
      is prevalent after successful simultaneous pancreas-kidney transplantation, and
      that this is associated with a high incidence of fractures, representing a cause
      for concern with regard to long-term morbidity. Contrary to the predominant
      trabecular bone loss expected with corticosteroid excess, cortical bone loss was
      prevalent in our patients, possibly due to pre-existing diabetic state and
      persistent hyperparathyroidism.

PMID- 9623563
TI  - Optimizing screening procedures for Staphylococcus aureus nasal carriage in
      patients on haemodialysis.
AB  - BACKGROUND: So far it remains unclear what the optimal screening method for
      detection of S. aureus nasal carriage in patients on haemodialysis is with regard
      to number of cultures performed, culture interval, and necessity of a broth
      enrichment procedure. METHODS: A prospective, uncontrolled study was performed at
      the renal unit of a tertiary care centre, including all haemodialysis patients
      (n=91) attending the unit during the study period. The purpose was to determine
      the optimal screening method for S. aureus nasal carriage in patients on
      haemodialysis. RESULTS: When compared to the conventional culture method,
      inclusion of a broth-enrichment procedure increased the number of cultures
      positive for S. aureus significantly (31 vs 24%, P<0.0001). Of 91 patients 37%
      were S. aureus carriers (defined as at least 1 of 5 cultures positive), 33% were
      stable carriers (defined as at least 2 of 5 cultures positive). Fourth and 5th
      cultures, taken at subsequent dialysis sessions, captured only two additional
      carriers (6% of all carriers). With respect to culture results and identification
      of carrier status a short (1-h) and a long (>24-h) sampling procedure showed no
      significantly different results. CONCLUSIONS: S. aureus nasal carriage in
      haemodialysis patients can be conveniently established with three nasal cultures
      taken with 1-h intervals, and the inclusion of a broth-enrichment procedure.

PMID- 9623564
TI  - Is atheroembolic disease a new differential diagnosis of pulmonary-renal
      syndrome?

PMID- 9623565
TI  - Cholesterol embolism and acute interstitial nephritis: two adverse effects of
      streptokinase thrombolytic therapy in the same patient.

PMID- 9623566
TI  - Uraemia after laparoscopic bilateral hernia repair.

PMID- 9623567
TI  - Acute renal failure due to aortocaval fistula.

PMID- 9623569
TI  - Autosomal recessive polycystic kidney disease presenting in adulthood. Molecular
      diagnosis of the family.

PMID- 9623568
TI  - Beta-cell dysfunction complicating haemolytic uraemic syndrome.

PMID- 9623570
TI  - Intractable dehydration in a patient on CAPD. Pathophysiological implications for
      the classification of peritoneal membrane alterations.

PMID- 9623571
TI  - No evidence of functional deterioration of renal graft after repeated pregnancies
      -a report on three women with 17 pregnancies.

PMID- 9623572
TI  - Ogilvie's syndrome following renal transplantation.

PMID- 9623573
TI  - Late 'spontaneous' kidney graft decapsulation with fluid collection: lymphocele
      or transudate?

PMID- 9623574
TI  - Lipoprotein glomerulopathy: a new cause of nephrotic syndrome after renal
      transplantation.

PMID- 9623575
TI  - The hypertensive lady with elevated plasma norepinephrine concentration and no
      demonstrable tumour--the search for pheochromocytoma.

PMID- 9623576
TI  - Pain and pyuria.

PMID- 9623577
TI  - Images in nephrology. Fibromuscular dysplasia in a transplanted kidney.

PMID- 9623578
TI  - The odyssey of a patient with hypocalciuric hypercalcaemia: pitfalls to consider.

PMID- 9623579
TI  - Preservation of renal function: the spectrum of effects by calcium channel
      blockers.

PMID- 9623580
TI  - Interferon-induced acute renal failure in nephrotic syndrome.

PMID- 9623581
TI  - Severe nephrotic syndrome requiring bilateral renal embolization for control:
      repeated recanalization despite presence of a hypercoagulable state.

PMID- 9623582
TI  - Treatment of relapsing thrombotic thrombocytopenic purpura with cyclophosphamide
      pulse therapy.

PMID- 9623583
TI  - Hydrocarbon exposure and glomerulonephritis due to systemic vasculitis.

PMID- 9623584
TI  - Plasma alpha-glutathione S-transferase (alpha-GST) as a marker of liver damage in
      hemodialysis patients.

PMID- 9623585
TI  - Measurement of gamma glutamyl transpeptidase activity: a useful and low-cost tool
      for the detection of HCV infection in haemodialysed patients.

PMID- 9623586
TI  - Improvement of liver function in a paediatric patient with biliary cirrhosis
      after triple immunosuppression with Mycophenolate following renal
      transplantation.

PMID- 9623587
TI  - Captopril renal scintigraphy before and after revascularization in a kidney
      transplanted patient.

PMID- 9623588
TI  - Successful use of oral valacyclovir in post-transplant cytomegalovirus infection
      in renal allograft recipients.

PMID- 9623589
TI  - Human follicle-stimulating hormone structure-activity relationships.

PMID- 9623590
TI  - The tie that binds: design of biologically active single-chain human chorionic
      gonadotropins and a gonadotropin-receptor complex using protein engineering.

PMID- 9623591
TI  - Transforming growth factor beta1 in the human endometrium. Cyclic variation,
      increased expression by estradiol and progesterone, and regulation of plasminogen
      activators and plasminogen activator inhibitor-1.
AB  - The purpose of this study was to identify cyclic variations and hormonal
      regulation of endometrial transforming growth factor beta1 (TGFbeta1) mRNA.
      Regulation of the plasminogen-activating system was also examined, since it is
      involved in activation of latent TGFbetas. We measured TGFbeta1 mRNA in 51 normal
      endometrial samples by Northern blot and densitometric scanning of
      autoradiograms. Each value was related to the corresponding beta-actin value to
      allow quantitative evaluation. TGFbeta1 mRNA was higher in the mid and late
      secretory and menstrual phases than in the earlier parts of the cycle. This
      pattern implies progesterone dependence. The content of TGFbeta1 mRNA in
      endometrial tissue explants obtained in the proliferative phase was significantly
      increased after stimulation for 4 days with estradiol + progesterone in vitro.
      Both TGFbeta1 and estradiol + progesterone increased the content of plasminogen
      activator inhibitor-1 mRNA and protein in primary cultures of endometrial stromal
      cells. Conditioned-medium concentrations of urokinase plasminogen activator (u
      PA) were increased by TGFbeta1, but decreased by estradiol + progesterone. This
      effect of estradiol + progesterone results from increased internalization and
      degradation of u-PA secondary to up-regulation of the cell surface receptor for u
      PA by progesterone (Casslen et al., JCEM 1995; 80: 2776-2784). Increased
      extracellular u-PA in response to TGFbeta1 exposure was thus in concordance with
      an unchanged amount of available u-PA receptors on the cell surface. The
      activation mechanism of latent TGFbeta involves u-PA activity; since u-PA
      activity is reduced in the secretory endometrium, we suggest that although
      TGFbeta1 mRNA is increased in the mid and late secretory phase, TGFbetas are
      mainly in their latent form until the premenstrual rise in u-PA activity
      stimulates activation. TGFbeta may promote capillary growth during endometrial
      regeneration.

PMID- 9623592
TI  - Differential expression pattern of retinoid X receptors in adult murine
      testicular cells implies varying roles for these receptors in spermatogenesis.
AB  - Retinoids have previously been shown to be crucial for normal spermatogenesis.
      The role of retinoic acid receptors has been studied, but relatively little is
      known about the function of retinoid X receptors (RXRs). To gain more insight in
      the function of RXRs during spermatogenesis, the cellular localization of RXRs in
      the mouse testis was examined using immunohistochemistry and RNase protection
      assays. In both normal and vitamin A-deficient (VAD) testes, a strong immune
      response to an RXRalpha antibody occurred in Leydig cells, peritubular myoid
      cells, and A spermatogonia. Weaker signals were found in spermatocytes and
      spermatids. In normal testes, an RXRbeta antibody gave a reaction in Leydig
      cells, and, to a lesser extent, in Sertoli cells, A spermatogonia, pachytene
      spermatocytes, and spermatids. In Leydig cells, a cytoplasmatic signal was found
      in addition to the nuclear signal. In the VAD testis, only Leydig cells and A
      spermatogonia were positive, which indicates that RXRbeta expression may be
      dependent on the retinoid status. Previous studies have shown RXRgamma mRNA
      expression in the mouse testis at a low level. Nevertheless, an RXRgamma antibody
      caused a strong immune response in interstitial cells and in A spermatogonia, and
      a weak signal in pachytene spermatocytes. These immunohistochemical data were
      supported by the results of RNase protection assays on mRNA of testicular cell
      isolations. In conclusion, the different RXRs in the mouse testis have distinct
      expression patterns, suggesting that they may have different functions.

PMID- 9623593
TI  - Parthenogenetic activation of pig oocytes with calcium ionophore and the block to
      sperm penetration after activation.
AB  - Calcium ionophore A23187 can parthenogenetically activate oocytes in many
      animals. The present study was designed to analyze functionally the mechanism of
      A23187 activation of pig oocytes matured in vitro. In experiment 1, effects of
      the concentration of A23187 on intracellular calcium transients, cortical granule
      (CG) exocytosis, nuclear activation, and zona reaction, which was determined by
      zona hardening and sperm penetrability, were examined. Cumulus-free oocytes were
      exposed to 0-100 microM A23187 for 5 min. It was found that the amplitude of the
      intracellular calcium transients, percentage of CG exocytosis, and percentage of
      pronuclear formation were increased in a concentration-dependent manner. The time
      for dissolution of zona pellucida (ZP) was increased in the oocytes treated with
      25-100 microM A23187. Penetration of ZP-intact oocytes by spermatozoa was
      decreased and only 3-4% of oocytes were penetrated by spermatozoa after 50-100
      microM A23187 treatment. In experiment 2, oocytes were treated with 100 microM
      A23187 for 5 min and then cultured for 10 min or 3.5 h before insemination. No
      difference in penetration rates was observed between the two groups of oocytes
      (12.0% vs. 12.2%), but the penetration rates were significantly lower than those
      in controls (85.2% vs. 82.4%). In experiment 3, treatment of oocytes with 100
      microM A23187 for 5 min was followed by removal of the ZP from a portion of the
      oocytes. ZP-intact and ZP-free oocytes were then inseminated for examination of
      sperm penetration. One of 65 (2%) oocytes with ZP and 48 of 52 (92%) oocytes
      without ZP were penetrated by spermatozoa. These results indicate that activation
      of pig oocytes by A23187 is the result of A23187-induced intracellular calcium
      increase and that A23187-induced cortical reaction can prevent sperm penetration
      of ZP-intact oocytes, but not ZP-free oocytes.

PMID- 9623594
TI  - Only a truncated epidermal growth factor receptor protein is present in porcine
      endometrium.
AB  - The epidermal growth factor receptor (EGF-R) is a 170-kDa transmembrane protein,
      of which a truncated 100-kDa form (trEGF-R) lacking the cytoplasmic and the
      transmembrane domains, and an oncogenic 68-kDa form (v-erb) lacking the
      extracellular domain have been described. The trEGF-R is secreted and not able to
      transmit signals into the cell. Growth factors of the EGF family have been shown
      in porcine uterine fluids and blastocyst. Employing differential
      immunohistochemistry, we found the extracellular domain, but not the cytoplasmic
      domain, of the EGF-R in porcine endometrium on Days 9-11 of pregnancy.
      Blastocysts from Days 9 to 11 post coitum (p.c.) were positive for both
      antibodies, indicating the presence of the full-size receptor. Western Blotting
      of endometrial protein resulted in a 100-kDa band, but no 170-kDa band. No
      evidence for a coexpression of the 170- or 68-kDa forms of the receptor was
      found. ELISA analysis demonstrated trEGF-R in porcine uterine flushings. We
      conclude that 1) the trEGF-R is the only EGF-R form present in porcine
      endometrium, and 2) growth factors of the EGF family in porcine uterine fluids
      can exert their function via the EGF-R only on blastocysts, not on the
      endometrium.

PMID- 9623595
TI  - Follicle dynamics and aromatase activity in high-ovulating Meishan sows and in
      Large-White hybrid contemporaries.
AB  - This study compared the dynamics of follicle development during the follicular
      phase in Meishan sows (n = 10) with a high ovulation rate, with those in
      contemporary Large-White hybrid sows (n = 12) (ovulation rates: 27.7 and 17.6,
      respectively; p < 0.01). Ovaries were recovered on Day 16 or 19 of the cycle, and
      all follicles > or = 1 mm in diameter were dissected. Fluid was aspirated from
      all those > or = 2 mm, and the granulosa and theca cells were incubated to
      estimate aromatase activity and estradiol production. The total number of
      follicles dissected was higher in Meishan than in Large-White hybrid animals (p <
      0.001), and whereas the number decreased (p < 0.01) between Days 16 and 19 in
      Large-White hybrid sows, there was no significant change in Meishan animals. The
      mean diameter of Meishan follicles recovered on each of Days 16 and 19 was
      smaller (p < 0.001) than that of those recovered from Large-White hybrids. Total
      estradiol production in vitro was higher (p < 0.01) by follicles > or = 2 mm from
      Meishan sows. There was an interaction (p < 0.01) between day of the cycle,
      breed, and follicle diameter in aromatase activity in both granulosa cells and
      theca tissue, and in follicular fluid estradiol concentrations in follicles > or
      = 2-< 6 mm. The largest three size categories of follicles recovered on Day 19
      from each breed were classified as preovulatory (29.0 and 17.7 for Meishan and
      Large-White hybrid, respectively), and the mean diameter was smaller (p < 0.001)
      in Meishan animals. Follicular fluid estradiol concentrations and total estradiol
      synthesis by granulosa and theca combined were higher (p < 0.05) in Meishan than
      in Large-White hybrid sows. In conclusion, high-ovulating Meishans maintained a
      higher number of follicles during the follicular phase, which overall synthesized
      more estradiol in vitro, than did Large-White hybrid animals.

PMID- 9623596
TI  - Regulation of 11beta-hydroxysteroid dehydrogenase type 2 by progesterone,
      estrogen, and the cyclic adenosine 5'-monophosphate pathway in cultured human
      placental and chorionic trophoblasts.
AB  - Human placenta and fetal membranes contain two types of 11beta-hydroxysteroid
      dehydrogenase (11beta-HSD). 11Beta-HSD1 interconverts cortisol and cortisone and
      is the predominant isoform found in the fetal membranes. 11Beta-HSD2, which
      predominates in the placenta syncytiotrophoblast, converts cortisol to cortisone.
      It has been proposed that placental 11beta-HSD protects the fetus from high
      levels of maternal glucocorticoids. In this study, cultured term human placental
      and chorionic trophoblasts were used to examine the regulation of 11beta-HSD1 and
      11beta-HSD2 activities and mRNA expression by progesterone, estrogen, and
      activators of adenylate cyclase (forskolin) and protein kinase C (phorbol 12
      myristate 13-acetate, PMA). Placental trophoblast displayed mainly type 2 oxidase
      activities. 11Beta-HSD in the chorionic trophoblast was exclusively an 11beta
      HSD1 reductase. Progesterone (0.001-1 microM) inhibited 11beta-HSD2 activity in a
      dose-dependent fashion. Inhibition of endogenous progesterone production with
      trilostane enhanced 11beta-HSD2 activity. The inhibitory effect of progesterone
      on 11beta-HSD2 activity was not reversed by the progesterone receptor antagonists
      RU-486 or onapristone. Progesterone (1 microM) also reduced levels of 11beta-HSD2
      mRNA, an effect that was attenuated by both RU-486 and onapristone. Estradiol (1
      microM) inhibited type 2 oxidase activity as well. Activation of adenylate
      cyclase by forskolin (100 microM) up-regulated both 11beta-HSD2 activity and mRNA
      expression; there was no effect of PMA (1 microM) on 11beta-HSD2. 11Beta-HSD1
      reductase activity was unaffected by progesterone, estrogen, forskolin, or PMA in
      either the placental or chorionic trophoblasts. We conclude that both
      progesterone and estrogen are inhibitors of 11beta-HSD2 activity in term human
      placenta in vitro. Levels of 11beta-HSD2 activity and mRNA are increased by
      activation of the cAMP pathway. Progesterone also suppresses levels of 11beta
      HSD2 mRNA.

PMID- 9623597
TI  - Amniotic fluid prolactin is decreased by experimental intrauterine infection or
      interleukin-1beta infusion but not via prostaglandins in pregnant rhesus
      macaques.
AB  - Amniotic fluid contains a high concentration of prolactin produced and secreted
      by the decidua. In vitro models have suggested that bacterial products inhibit
      prolactin secretion by decidual cells. To further examine this potentially
      important regulatory mechanism in the whole animal, chronically instrumented
      pregnant rhesus monkeys were prepared. Experimental infection was induced by
      intraamniotic or choriodecidual inoculation of 10(3)-10(6) group B streptococcus.
      Alternatively, interleukin (IL)-1beta was infused into the amniotic cavity.
      Finally, indomethacin was coadministered with IL-1beta to block the production of
      prostaglandins (PGs). The average prolactin level prior to inoculation (0 h)
      equaled 34.0 +/- 6.4 microg/ml. There was a 40% decrease in prolactin by 37 h
      postinfection (n = 6) and a 71% decrease between 61 and 72 h postinfection (n =
      3, p < 0.01 vs. before infection). Infusion of IL-1beta also caused a decrease in
      amniotic fluid prolactin. There was a 42% decrease in prolactin between 0 and 24
      h postinfusion (p < 0.05) and a 66% decrease between 25 and 72 h after IL-1beta
      infusion (p < 0.05; n = 6). Coadministration of indomethacin with IL-1beta
      prevented the accompanying increase in PGs but did not prevent the decrease in
      prolactin (n = 5). Amniotic fluid prolactin levels in untreated monkeys were
      stable and without a prepartum decline during the sampling period from 130 to 166
      days of gestation. In summary, intrauterine bacterial infection decreases
      amniotic fluid prolactin, and IL-1beta mimics this effect. The effect of IL-1beta
      on amniotic fluid prolactin does not appear to be mediated by PGs and may involve
      a direct effect of IL-1beta on decidual cells.

PMID- 9623598
TI  - Specific non-genomic, membrane-localized binding sites for progesterone in the
      bovine corpus luteum.
AB  - Fractionation of bovine corpus luteum (CL) homogenates on continuous sucrose
      density gradients with and without preincubation with 3H-progesterone
      demonstrated high levels of tracer binding and high content of endogenous
      progesterone associated with particulate membrane fractions. Analysis of gradient
      fractions for a range of luteal plasma membrane and intracellular organelle
      marker enzyme activities indicated that endogenous progesterone content and 3H
      progesterone-binding activity were associated with fractions enriched in luteal
      plasma membrane markers. This was confirmed by pretreatment of homogenates with
      the saponin, digitonin, prior to fractionation. Digitonin perturbed the buoyant
      density of luteal surface membrane markers and 3H-progesterone binding to a
      similar extent, but did not perturb the buoyant densities of other intracellular
      markers to the same degree. Interestingly, digitonin pretreatment also increased
      the proportion of progesterone tracer that entered the gradients. We consistently
      failed to demonstrate significant binding of 3H-progesterone to membrane
      fractions incubated with progesterone tracer in vitro. However, when digitonin
      was included in the in vitro binding assay, we observed a dramatic, dose
      dependent stimulation of 3H-progesterone binding by digitonin. Other radiolabeled
      steroids tested (3H-cortisol, 3H-testosterone) bound poorly in the presence or
      absence of digitonin. 3H-Progesterone binding in the presence of optimal
      digitonin concentrations increased linearly with increasing luteal membrane
      concentration; was dependent on the pH, duration, and temperature of incubation;
      and low levels of progesterone (68 nM) competed for tracer binding. A range of
      other steroids tested (androgens, estrogens, corticosteroids, steroid precursors)
      competed at higher concentrations (10- to 100-fold) or did not compete at all for
      3H-progesterone binding. There was no correlation between the hydrophobicity of
      various steroids and their ability to compete for binding. Moreover, a number of
      agonists and antagonists specific for the genomic progesterone receptor, agonists
      of peripheral benzodiazepine receptors, and inhibitors of a range of
      steroidogenic enzymes did not compete for 3H-progesterone binding. Western blots
      confirmed that detergent-solubilized progesterone-binding sites could be resolved
      from cytochrome P450 side-chain cleavage and 3beta-hydroxysteroid dehydrogenase.
      Moreover, extraction of bound steroid from the binding site and HPLC demonstrated
      identity to progesterone, suggesting that no metabolism of the progesterone
      tracer had occurred during incubation. Progesterone binding to membranes of large
      luteal cells was higher compared with binding to small luteal cells, and levels
      were similar in membranes prepared from CL at all stages of the luteal phase. We
      suggest that bovine luteal progesterone-binding sites may play a role either in
      sequestration of newly synthesized progesterone or in the mediation of autocrine
      and/or paracrine actions of progesterone in the CL.

PMID- 9623599
TI  - Analysis of mouse oocyte activation suggests the involvement of sperm perinuclear
      material.
AB  - The mouse oocyte can be activated by injection of a single, intact mouse
      spermatozoon or its isolated head. Isolated tails are unable to activate the
      oocyte. Active sperm-borne oocyte-activating factor(s) (SOAF) appears during
      transformation of the round spermatid into the spermatozoon. The action of SOAF
      is not highly species-specific: mouse oocytes are activated by injection of
      spermatozoa from foreign species, such as the hamster, rabbit, pig, human, and
      even fish. Some SOAF can be extracted by simple freeze-thawing of (hamster)
      spermatozoa; additional SOAF is obtained by sequential treatment of spermatozoa
      with Triton X-100 and SDS. Electron microscopic examination of sperm heads during
      SOAF extraction suggests that the relatively insoluble SOAF is associated with
      perinuclear material. When microsurgically injected into oocytes, Triton X-100
      treated sperm heads (with perinuclear material, but without any membranes) can
      activate the oocytes, leading to normal embryonic development. Whereas
      perinuclear components have been believed to play a purely structural role, these
      data suggest an additional function for them in oocyte activation.

PMID- 9623600
TI  - Impact of tumor necrosis factor alpha on mouse embryonic stem cells.
AB  - Previous studies have shown the adverse impact of the cytokine tumor necrosis
      factor alpha (TNFalpha) on the development of the inner cell mass in mouse
      blastocysts. In the present study, two embryonic stem (ES) cell lines were used
      to further investigate the action of TNFalpha. The expression of TNFalpha
      receptors in ES cells was tested by reverse transcription-polymerase chain
      reaction and Northern blot analysis. Transcripts encoding the two distinct
      receptor isoforms were detected in these cells. Using different approaches, our
      data showed a TNFalpha dose-dependent decrease in the number of ES cells after 24
      h of exposure. Simultaneous blocking of the two receptors with antagonist
      antibodies was needed to completely abrogate the inhibitory effect of the
      cytokine. Extensive DNA nicks (visualized by the terminal deoxynucleotidyl
      transferase-mediated deoxyuridine triphosphate nick end-labeling [TUNEL] method),
      but not nuclear fragmentation, was found with a higher incidence in ES cells
      exposed to TNFalpha. The possibility that TNFalpha may stimulate ES cell
      differentiation was investigated with a test based on the expression of alkaline
      phosphatase. The results indicated that TNFalpha cannot over-ride the negative
      control exerted by leukemia inhibitory factor on differentiation. The opposite
      possibility, that TNFalpha blocks differentiation, was tested in suspended medium
      drops. In this system, TNFalpha was found to decrease the ability of ES cells to
      differentiate into embryoid bodies. In addition, expression of Rex-1, a marker
      gene for undifferentiated ES cells, was increased in ES cells exposed to
      TNFalpha. Thus our data support the hypothesis that TNFalpha is a significant
      (negative) effector of proliferation and differentiation in inner cell mass
      derived ES cells.

PMID- 9623601
TI  - Reactivating tammar wallaby blastocysts oxidize glucose.
AB  - Metabolic reactivation of the tammar blastocyst appears to be characterized by a
      change in the pathway of glucose metabolism rather than an absolute increase in
      substrate uptake. The switch in type of metabolism used was examined to gain
      information on the timing and physiology of blastocyst reactivation. Fluorescent
      and radioisotope techniques were used sequentially to determine the activity of
      pathways of glucose metabolism by individual wallaby blastocysts during diapause
      and 3, 4, 5, 6, 7, 8, and 10 days after removal of pouch young (RPY). Maternal
      endometrial and luteal cell metabolism and circulating hormone levels were
      measured and correlated with blastocyst activity. Observed differences between
      rates of blastocyst reactivation could be explained by variation in the maternal
      response between animals. While blastocysts recovered 4 days after RPY oxidized
      more glucose compared with Day 0 blastocysts (p < 0.05), rates of glycolysis did
      not change until Day 10. Blastocysts recovered between 4 and 10 days after RPY
      oxidized a significantly greater percentage of the glucose taken up (p < 0.01).
      The reduced ATP:ADP ratio within blastocysts recovered 3 days after RPY (p <
      0.05) indicates that conditions are suitable for blastocysts to undergo a
      metabolic switch from glycolytic to oxidative metabolism of glucose on Day 4
      after RPY. The increased oxidation results in greater ATP production, which
      plausibly fuels the increased energy requirements of wallaby blastocysts during
      the early stages of reactivation.

PMID- 9623602
TI  - Effects of melengestrol acetate on onset of puberty, follicular growth, and
      patterns of luteinizing hormone secretion in beef heifers.
AB  - Our objective was to test the hypothesis that short-term (8 days) treatment of
      prepubertal heifers with melengestrol acetate (MGA) and subsequent steroid
      withdrawal would stimulate LH secretion and follicular growth. Angus heifers were
      divided randomly into two groups; MGA-treated (n = 8) or control (CON; n = 9).
      Puberty was determined by monitoring circulating concentrations of progesterone
      and ovarian morphology during a 14-day period following MGA withdrawal. LH
      secretory patterns were assessed upon initiation of MGA (Day 0), during MGA (Day
      7), and 1 day after withdrawal of MGA (Day 9). All MGA-treated heifers, versus
      four CON heifers, exhibited corpora lutea and luteal phase concentrations of
      progesterone within 10 days after treatment (p = 0.01). Mean LH and LH pulse
      frequency increased (p = 0.005 and 0.0001, respectively) between Days 0 and 9 in
      MGA-treated heifers. In CON heifers, mean LH concentrations and pulse frequencies
      did not change. During the same period, diameter of the largest follicle
      increased in MGA-treated animals (p = 0.003) but did not change in the CON
      heifers. On the basis of these results, we suggest that MGA withdrawal enhances
      onset of puberty by stimulating pulsatile LH secretion that accelerates follicle
      growth to the preovulatory stage.

PMID- 9623603
TI  - Creatine synthesis and transport systems in the male rat reproductive tract.
AB  - Previous studies from this laboratory showed that high levels of guanidinoacetate
      methyltransferase are present in mouse testis and epididymis, whereas
      guanidinoacetate methyltransferase mRNA and protein are not detected in seminal
      vesicles where large amounts of creatine (Cr) and phosphocreatine are found (Lee
      et al., Biol Reprod 1994; 50:152-162). To further investigate the origin(s) of Cr
      in the male reproductive tract, the expression patterns of the three enzymes and
      a transporter involved in Cr metabolism were examined with rat reproductive
      tissues. Western blot analysis showed that expression of L-arginine:glycine
      amidinotransferase was limited to the kidney. On the other hand, high levels of
      the mRNAs for both guanidinoacetate methyltransferase and Sadenosylhomocysteine
      hydrolase were expressed in the testis and epididymis as well as the liver and
      kidney. Cr transporter mRNA was highly expressed in the seminal vesicle and vas
      deferens. These results suggest that the source of Cr in the male reproductive
      tract varies depending on the tissue; in the testes and epididymides, Cr is
      synthesized from guanidinoacetate, while in the seminal vesicles, Cr is
      transported from blood. Previous and present findings suggest the importance of
      Cr metabolism and/or transport for reproductive functions.

PMID- 9623604
TI  - Resumption of follicular waves in beef cows is not associated with periparturient
      changes in follicle-stimulating hormone heterogeneity despite major changes in
      steroid and luteinizing hormone concentrations.
AB  - To test the hypothesis that emergence of follicle waves postpartum is associated
      with a change in circulating FSH isoform distribution, 10 Limousin-cross suckler
      cows were blood sampled daily from 5 wk prepartum until first ovulation
      postpartum for FSH, LH, estradiol (E2), and progesterone assay. Follicular growth
      was monitored daily by ultrasonography from Days 5 to 10 postpartum until first
      ovulation. Distributions of circulating FSH isoforms were characterized (n = 4
      per group) by chromatofocusing at 1) 18-33 days prepartum, 2) 3-5 days prepartum,
      3) the first postpartum FSH rise responsible for emergence of the first follicle
      wave, and 4) the FSH rise that stimulated the ovulatory follicle wave. The
      interval to detection of the first postpartum dominant follicle (DF) was 9.6 +/-
      0.58 days. The number of DF before first ovulation was 2.1 +/- 0.18, and first
      ovulation occurred at 28.6 +/- 1.54 days postpartum. Serum E2 concentrations were
      higher (p = 0.0001) in cows during the 5-wk period prepartum (53.8 +/- 6.29
      pg/ml) than in the postpartum period up to first ovulation (1.5 +/- 0.15 pg/ml).
      In late pregnancy, there was an absence of recurrent FSH rises and LH
      concentrations were decreased (p < 0.0001) compared with those in the postpartum
      period. The emergence of each follicle wave postpartum was preceded by a 2- to 4
      day rise in FSH concentrations. The pattern of FSH isoform distribution did not
      differ (p > or = 0.75) between the pre- and postpartum periods.

PMID- 9623605
TI  - Insulin-like and fibroblast growth factors and their receptors are differentially
      expressed in the oviducts of the common marmoset monkey (Callithrix jacchus)
      during the ovulatory cycle.
AB  - It is suggested that growth factors support the process of maturation and
      differentiation in the mammalian oviduct. Fibroblast growth factors (FGF) and
      insulin-like growth factors (IGF) are possible influences on these processes. The
      present study describes for the first time the expression of FGF-1 and -2 and
      their receptors as well as IGF-1 and -2 and the corresponding IGF receptor type 1
      in the oviduct of the New World monkey Callithrix jacchus. Because of the limited
      RNA yields from oviducts, reverse transcription-polymerase chain reaction (RT
      PCR) was performed to estimate expression levels. Expression patterns were found
      to be similar for all examined growth factors and receptors: the highest mRNA
      contents were obtained at the late proliferative and early to midsecretory
      phases, compared with lower levels during the early proliferative phase. Elevated
      amounts of these RNAs were correlated with high serum estradiol but not with
      progesterone concentrations. Each PCR product showed a high degree of homology (>
      92%) to the known human sequences. Immunohistochemical analysis indicated greater
      specific staining for FGF-1 and -2 and IGF-1 before ovulation on the luminal
      epithelial surface of marmoset oviducts in comparison to the other cycle phases.
      Differences in staining intensity were not observed between the ampulla and
      isthmus. In summary, the marmoset oviduct expresses all components of functional
      FGF and IGF systems, thus suggesting auto-/paracrine effects of these growth
      factors within the primate oviduct, possibly under the control of estrogenic
      hormones.

PMID- 9623606
TI  - Repeated acute activation of the hypothalamo-pituitary adrenal axis prior to and
      during estrus did not affect reproductive performance in gilts.
AB  - We investigated the effects of repeated acute activation of the hypothalamo
      pituitary adrenal axis, prior to and during estrus, on reproduction in gilts.
      Individual gilts (n = 24 per treatment) either served as controls or were
      subjected to daily acute stress ("negative handling," brief electric shock with a
      battery-operated prodder during confinement with the experimenter) commencing, on
      average, 8 days prior to estrus. Gilts subjected to negative handling had a
      significant elevation in plasma concentrations of cortisol that lasted at least 3
      4 h, and these gilts were slower than control gilts to approach and interact with
      the experimenter in a standard test. Nevertheless, reproductive performance--as
      measured by sexual receptivity and proceptivity, ovulation, the percentage of
      gilts that became pregnant, the number of embryos 20-21 days after insemination,
      and the weight of embryos--was not affected by repeated acute activation of the
      hypothalamo-pituitary adrenal axis. Our results suggest that repeated acute
      activation of the hypothalamo-pituitary adrenal axis prior to and during estrus
      does not affect the factors that control estrus and ovulation in gilts.

PMID- 9623607
TI  - Loss of the signature six carboxyl amino acid tail from ovine interferon-tau does
      not affect biological activity.
AB  - Interferon-tau (IFN-tau) is a type I IFN that is secreted from conceptuses of
      Bovidae (sheep, cattle, and related ruminant ungulates) for a few days during
      early pregnancy. It acts to prolong the life span of the corpus luteum. All
      secreted forms of IFN-tau, like the related IFN-omega, are 172 amino acids in
      length and differ from IFN-alpha and -beta by the presence of six additional
      amino acids at their carboxyl termini. The aim of this study was to determine
      whether this carboxyl tail was important for biological activity of IFN-tau,
      particularly for its antiluteolytic function in ewes. Full-length ovine IFN-tau
      (p3) and a mutated form truncated by six amino acids at its carboxyl terminal
      (p3Trn6, 166 amino acids) were produced in Escherichia coli. Both proteins had
      similar antiviral activities (2.12 +/- 0.92 x 10(8) IU/mg for p3; 1.96 +/- 0.58 x
      10(8) IU/mg for p3Trn6) when tested on Madin-Darby bovine kidney (MDBK) cells.
      Antiproliferative activity, as measured on human Daudi cells by determining the
      protein concentration required to inhibit growth by 50%, was slightly higher (p <
      0.05) for p3Trn6 (7.36 +/- 0.46 pM) than for p3 (13.99 +/- 0.85 pM). Most
      importantly, p3 and p3Trn6 were equally capable of prolonging the life span of
      the corpus luteum of nonpregnant ewes when the proteins were administered at
      doses of either 60 or 300 microg/day into the uterine lumen through indwelling
      uterine cannulae from Day 10 to Day 18 postestrus. Therefore, the carboxyl
      terminal amino acid extension for IFN-tau does not appear to serve a functional
      role in the action of these proteins.

PMID- 9623608
TI  - Complexity in uterine macrophage responses to cytokines in mice.
AB  - Uterine stromal macrophages change dramatically in density and morphology through
      the estrous cycle and during early pregnancy, whereas those in the mesometrial
      triangle do not undergo these changes. The mononuclear phagocytic growth factor,
      colony-stimulating factor-1 (CSF-1), regulates both the density and morphology of
      uterine macrophage populations, as shown by the fact that uterine macrophages are
      depleted and more rounded in the absence of CSF-1 caused by the osteopetrotic
      (csfm(op)) null mutation, compared to those of normal mice. Restoration of
      circulating CSF-1 to the nullizygous mice did not affect stromal macrophage
      density although it restored the population in the mesometrial triangle. This
      suggests CSF-1 regulation of these macrophage populations by local and humoral
      routes, respectively. Nevertheless, even in the absence of CSF-1, stromal
      macrophage population density varies 30-fold through the estrous cycle,
      suggesting the involvement in their regulation of factors other than CSF-1, such
      as the chemokines, which are chemoattractive for macrophages. The mRNA for the
      chemokines JE (MCP-1), C10, RANTES, and MIP1alpha are expressed in the uterus,
      with elevated levels observed on the first day of pregnancy. Such molecules,
      together with CSF-1, may play a role in modulating the complexities of uterine
      macrophage dynamics in response to sex steroid hormones and mating.

PMID- 9623609
TI  - Extracellular signal-regulated kinases modulate capacitation of human
      spermatozoa.
AB  - Recent evidence indicates the presence of p21 Ras and of a protein with
      characteristics similar to mitogen-activated protein kinases (MAPKs), also known
      as extracellular signal-regulated kinases (ERKs), in mammalian spermatozoa,
      suggesting the occurrence of the Ras/ERK cascade in these cells. In the present
      study we investigated the subcellular localization of ERKs and their biological
      functions in human spermatozoa. Immunohistochemistry, immunofluorescence,
      confocal microscopy, and immunoelectron microscopy demonstrated localization of
      ERKs in the postacrosomal region of spermatozoa. After stimulation of acrosome
      reaction with the calcium ionophore A23187 and progesterone, ERKs were mostly
      localized at the level of the equatorial region, indicating redistribution of
      these proteins in acrosome-reacted spermatozoa. Two proteins of 42 and 44 kDa
      that are tyrosine phosphorylated in a time-dependent manner during in vitro
      capacitation were identified as p42 (ERK-2) and p44 (ERK-1) by means of specific
      antibodies. The increase in tyrosine phosphorylation of these proteins during
      capacitation was accompanied by increased kinase activity, as determined by the
      ability of ERK-1 and ERK-2 to phosphorylate the substrate myelin basic protein.
      The role of this activity in the occurrence of sperm capacitation was also
      investigated by using PD098059, an inhibitor of the MAPK cascade. The presence of
      this compound during in vitro capacitation inhibits ERK activation and
      significantly reduces the ability of spermatozoa to undergo the acrosome reaction
      in response to progesterone. Since only capacitated spermatozoa are able to
      respond to progesterone, these data strongly indicate that ERKs are involved in
      the regulation of capacitation. In summary, our data demonstrate the presence of
      functional ERKs in human spermatozoa and indicate that these enzymes are involved
      in activation of these cells during capacitation, providing new insight in
      clarifying the molecular mechanisms and the signal transduction pathways of this
      process.

PMID- 9623610
TI  - Effects of cannabinoids on preimplantation mouse embryo development and
      implantation are mediated by brain-type cannabinoid receptors.
AB  - We examined the relative importance of G (Gi) protein-coupled brain-type (CB1-R)
      and spleen-type (CB2-R) cannabinoid receptors in preimplantation embryo
      development using agonists and antagonists specific to CB1-R and CB2-R. The
      results establish that endogenous cannabinoid ligands, anandamide and sn-2
      arachidonoylglycerol, arrest embryo development in vitro, and this effect is
      reversed by CB1-R antagonists SR141716A or AM 251, but not by SR144528, a CB2-R
      antagonist. A CB2-R selective agonist AM 663 failed to affect embryo development.
      These results suggest that cannabinoid effects on embryo development are mediated
      by CB1-R. We also observed that delta9-tetrahydrocannabinol ([-]THC) infused in
      the presence of cytochrome P450 inhibitors interfered with blastocyst
      implantation. This adverse effect was reversed by coinfusion of SR141716A. The
      less active stereoisomer (+)THC plus the inhibitors failed to affect
      implantation. Analysis of tissue levels demonstrated that uterine accumulation of
      (-)THC occurred when it was infused in the presence of the P450 inhibitors. These
      results demonstrate that the uterus and perhaps the embryo have the cytochrome
      P450 enzymes to metabolize (-)THC and neutralize its adverse effects on
      implantation. Collectively, the present study demonstrates that cannabinoid
      effects on embryo development and implantation are mediated by embryonic and/or
      uterine CB1-R, but not CB2-R.

PMID- 9623611
TI  - Regulation of expression of A-kinase anchoring proteins in rat granulosa cells.
AB  - FSH action on granulosa cells involves the generation of cAMP and subsequent
      activation of the cAMP-dependent protein kinase (PKA). The PKA holoenzyme is
      targeted to specific subcellular sites through the interaction of the regulatory
      subunits with A-kinase anchoring proteins (AKAPs). We previously reported that
      FSH regulates expression of AKAPs. In this report we examine the relationship
      between AKAP expression and cell shape. Granulosa cells cultured in the absence
      of FSH tend to spread and flatten. Cell spreading is accompanied by an increased
      expression of a 140-kDa AKAP. This spreading/flattening phenotype is independent
      of the specific extracellular matrix proteins (fibronectin, polylysine, and
      gelatin) on which cells are plated. Addition of FSH prevents both cell spreading
      and induction of AKAP 140. Culturing cells on poly (2-hydroxyethyl methacrylate),
      a surface-coating agent that inhibits cell spreading and adhesion, also inhibits
      expression of AKAP 140. Addition of phorbol myristate acetate, an agent known to
      antagonize FSH actions, blocks FSH regulation of both cell shape and AKAP 140
      expression. Addition of dexamethasone plus FSH causes a synergistic increase in
      progesterone levels but has no effect on cell shape or induction of AKAP 140.
      Dexamethasone produces a dose-dependent increase in AKAP 80 expression, which is
      blocked by FSH, suggesting cross talk between the glucocorticoid and FSH receptor
      signaling pathways. These data suggest that expression of AKAP 140 is linked to
      regulation of cell shape, and that changes in the expression of AKAPs are
      regulated by several different signaling pathways.

PMID- 9623612
TI  - Reduction of mucin-1 expression during the receptive phase in the rat uterus.
AB  - Mucin-1 (Muc1), an integral membrane mucin, is expressed on the apical surface of
      uterine epithelial cells (UE) of various species. Loss of Muc1 is believed to be
      necessary for embryo attachment. Muc1 expression is markedly reduced in luminal
      epithelia during the receptive phase in mice, baboons, and pigs. In the present
      study, we examined Muc1 expression during the rat estrous cycle and at Day 5 of
      pregnancy, the time of embryo attachment. In contrast to findings in the mouse,
      indirect immunofluorescence revealed that uterine Muc1 protein expression was
      unaltered during the estrous cycle. However, similar to what is observed in the
      mouse and other species, Muc1 protein decreased at Day 5 of pregnancy in luminal
      UE. The decrease in Muc1 expression was specific to luminal UE and did not occur
      in glandular UE. A partial cDNA corresponding to the cytoplasmic tail region of
      rat Muc1 was generated by a reverse transcription-polymerase chain reaction (RT
      PCR) strategy. This cDNA sequence is 89% and 91% identical to the corresponding
      region of mouse Muc1 at the nucleotide and amino acid levels, respectively. The
      predicted sequence of rat Muc1 protein has 70-90% identity to the Muc1 protein
      sequence obtained in other species. Semiquantitative RT-PCR experiments indicated
      that the mRNA encoding rat Muc1 decreased 57% at Day 5 as compared with the
      levels found at estrus. This value included mRNA from both luminal and glandular
      UE and so may underestimate the relative decrease in mRNA in the luminal
      compartment. In conclusion, we have determined that the levels of rat Muc1
      protein and mRNA decrease in the luminal UE at the time of implantation, a
      pattern similar to that seen in the mouse, baboon, and pig. This supports the
      general theory that reduction of Muc1 expression is necessary for embryo
      implantation.

PMID- 9623613
TI  - Intrafollicular insulin-like growth factor-binding protein levels in equine
      ovarian follicles during preovulatory maturation and regression.
AB  - The profiles of insulin-like growth factor-binding proteins (IGFBPs) in
      follicular fluid have been characterized in a number of mammals (rats, pigs,
      sheep, cattle, humans) and are good indicators of follicular status. We studied
      the IGFBP profiles of equine serum and ovarian follicular fluid recovered at
      various stages of the follicular phase. The levels of IGFBPs were related to the
      morphology and the steroidogenic activity of the follicles. Follicular fluids
      were recovered by ultrasound-guided follicular aspiration. In the first
      experiment, the dominant follicles of 10 mares were partly punctured (aspiration
      of 0.5-2.2 ml of fluid) once at the early dominant stage (22-25 mm in diameter)
      and a second time at the preovulatory stage (PO), 34 h after induction of
      ovulation. Among these 10 PO follicles, 5 were classified as healthy whereas the
      other 5 were classified as hemorrhagic, as assessed by ultrasonic morphology and
      subsequent ovulation or not. In another group of mares (n = 5), the largest
      follicle was punctured once at the late dominant stage (33-35 mm in diameter) and
      then at the PO stage, 34 h after induction of ovulation. Serum was prepared at
      each puncture session. In the second experiment, follicular fluid was recovered
      from the dominant and contemporary cohort subordinate follicles (n = 5 mares).
      Samples were individually assayed for estradiol-17beta and progesterone content
      by RIA, and IGFBPs were studied by using Western ligand blotting and
      densitometry. Equine serum and follicular fluid displayed IGFBP at 42-44 kDa
      (likely corresponding to IGFBP-3), 28-32 kDa (likely corresponding to IGFBP-5),
      24 kDa (likely corresponding to IGFBP-4), and 35 kDa, identified as IGFBP-2 by
      immunoblotting, plus one band at 120 kDa. IGFBP were clearly more abundant in
      serum than in fluid from healthy follicles. In the follicular fluid, 42-44-kDa
      IGFBP was the major binding protein, and its level was almost constant at the
      various physiological statuses studied. Follicular development of the dominant
      follicle in each mare was characterized by a decrease in intrafollicular IGFBP-2
      and 28-32-kDa IGFBP levels before LH stimulation and by an increase in IGFBP-2
      after LH stimulation. Follicular regression of large follicles, as well as
      subordinate ones, was characterized by a low level of intrafollicular estradiol
      17beta and was associated with an increase in IGFBP-2, 24-kDa IGFBP, and 28-32
      kDa IGFBP intrafollicular levels. Taking these results together, we have
      demonstrated clear correlations between the intrafollicular levels of estradiol
      17beta and IGFBP-2 and 28-32-kDa IGFBP. Therefore, follicular growth and
      regression in the mare are associated with specific changes in IGFBP levels.
      These changes could be of crucial importance for follicular development in
      ovulation or atresia.

PMID- 9623614
TI  - Spermicidal activity of metallocene complexes containing vanadium(IV) in humans.
AB  - We have used computer-assisted sperm analysis (CASA) to evaluate the spermicidal
      activity of 8 metallocene dihalides (vanadocene dichloride [VDC], titanocene
      dichloride [TDC], zirconocene dichloride [ZDC], molybdocene dichloride [MDC],
      hafnocene dichloride [HDC], vanadocene dibromide [VDB],
      bis[methylcyclopentadienyl] vanadium dichloride [VMDC], and vanadocene diiodide
      [VDI]); 5 vanadocene di-pseudohalides (vanadocene diazide [VDA], vanadocene
      dicyanide [VDCN], vanadocene dioxycyanate [VDOCN], vanadocene dithiocyanate
      [VDSCN], and vanadocene diselenocyanate [VDSeCN]); and 3 disubstituted
      derivatives (vanadocene ditriflate [VDT], vanadocene monochloro oxycyanate
      [VDCO], and vanadocene monochloro acetonitrilo tetrachloro ferrate [VDFe]).
      Whereas the metallocene complexes containing titanium, zirconium, molybdenum, and
      hafnodium were inactive, all 12 vanadocene complexes elicited potent spermicidal
      activity at nano-micromolar concentrations with an order of efficacy VDSeCN >
      VDSCN > VDB > VMDC > VDCN > VDA > VDC > VDOCN > VDI > VDT > VDFe > VDCO without
      disrupting the acrosomal membrane, as determined by high-resolution low-voltage
      scanning electron microscopy. The sperm-immobilizing activity of the vanadocene
      complexes was rapid and irreversible, since the treated sperm underwent apoptosis
      as determined by the flow cytometric annexin V binding assay, DNA nick end
      labeling, and confocal laser scanning microscopy. These results provide
      unprecedented evidence that metallocene complexes containing vanadium(IV),
      especially VDSeCN, may be useful as contraceptive agents.

PMID- 9623615
TI  - Follicle size-dependent induction of prostaglandin G/H synthase-2 during
      superovulation in cattle.
AB  - Under physiological conditions, prostaglandin G/H synthase-2 (PGHS-2) is induced
      in bovine preovulatory follicles by the endogenous surge of gonadotropins. To
      characterize the pattern of follicular PGHS-2 expression during superovulation in
      cattle, heifers were treated with exogenous FSH and ovulation was induced with
      hCG. Animals were ovariectomized 0, 18, and 24 h post-hCG, and extracts of
      follicles > or = 6 mm were analyzed by Western blotting. Follicular fluid
      concentrations of prostaglandin (PG) E2, PGF2alpha, progesterone, and estradiol
      17beta were determined by RIAs, and the morphology of the cumulus oocyte complex
      was examined. Results showed that PGHS-2 protein was absent in all follicles
      isolated at 0 h post-hCG (n = 119) and in small follicles (6 to < 8 mm) isolated
      between 0 and 24 h post-hCG (n = 27 follicles). In contrast, 12.3% of medium (8
      to < 10 mm) and 43.7% of large (> or = 10 mm) follicles were PGHS-2-positive at
      18 h post-hCG, and these percentages rose at 24 h to 45.9% and 91.0% in medium
      and large follicles, respectively (p < 0.05). Follicular fluid concentrations of
      PGE2 and PGF2alpha were low in follicles isolated at 0 h and increased only in
      PGHS-2-positive follicles isolated 24 h post-hCG (p < 0.05). Concentrations of
      progesterone and estradiol-17beta at 0 h were 28.2 +/- 5.8 and 291.8 +/- 13.0
      ng/ml, respectively, and a shift from estradiol-17beta to progesterone dominance
      (luteinization) occurred at 24 h post-hCG only in PGHS-2-positive follicles.
      Also, expansion of the cumulus oocyte complex was detected at 24 h post-hCG only
      in PGHS-2-positive follicles. Lack of PGHS-2 induction in follicles of ovulatory
      size (> 8 mm) was associated with an apparent failure to respond to hCG (absence
      of luteinization and cumulus expansion). Collectively, these results demonstrate
      the presence of a time- and follicle size-dependent induction of PGHS-2 in bovine
      follicles during superovulatory treatment and suggest that PGHS-2 expression can
      be used as a marker for follicular commitment to ovulation during ovarian
      hyperstimulation protocols.

PMID- 9623616
TI  - Caspase-3 in the rat ovary: localization and possible role in follicular atresia
      and luteal regression.
AB  - Apoptosis, the cellular mechanism of ovarian follicular atresia and luteal
      regression, is triggered by the activation of a proteolytic cascade of cysteine
      aspartate-specific proteases (caspases). The principle downstream effector of
      cell death is caspase-3, but little is known about the role or regulation of this
      enzyme in ovarian apoptosis. Two substrates of caspase-3, actin and poly(ADP
      ribose) polymerase (PARP), are inhibitors of DNase I, which is the endonuclease
      responsible for ovarian apoptotic DNA degradation. We therefore investigated the
      proteolytic cleavage of actin and PARP as well as the localization of caspase-3
      during follicular atresia (induced by gonadotropin withdrawal) and luteal
      regression (induced by prostaglandin F2alpha) in the rat ovary. Apoptotic DNA
      degradation was evident during both follicular atresia and luteal regression, but
      cleavage of PARP and actin was observed only during luteal regression. Caspase-3
      was localized in luteal cells of healthy corpora lutea (CL) and in theca, but not
      in granulosa cells of healthy follicles. However, caspase-3 immunostaining was
      evident in granulosa cells of atretic follicles in a pattern similar to that of
      the localization of granulosa cell death. There was no difference between healthy
      and apoptotic CL in the distribution or intensity of caspase-3 staining. These
      results demonstrate that the cleavage of actin and PARP are not necessary for
      activation of apoptotic DNA degradation during ovarian apoptosis. In addition,
      the presence of caspase-3 in granulosa cells of atretic, but not healthy,
      follicles suggests that the expression of this enzyme is regulated by
      gonadotropin and may be up-regulated as part of the apoptotic process in
      granulosa cells.

PMID- 9623617
TI  - Contemporary management of cystinuric patients.
AB  - Cystinuria is an inherited genetic disorder that results in excessive cystine
      excretion through defects in renal dibasic amino acid transport. Due to the
      relative insolubility of cystine in urine, patients with this condition are prone
      to progressive and recurrent episodes of stone formation. Medical treatment is
      aimed at decreasing the concentration of cystine in the urine as well as
      increasing its solubility. A standard regimen includes dietary manipulation with
      hydration and moderate salt restriction, alkalinization, and thiol derivatives.
      Despite aggressive medical management, cystinuric patients are likely to suffer
      stone recurrences, and urologic intervention often is required. Contemporary
      technology permits the use of minimally invasive techniques for the majority of
      these patients, and advances in shock wave lithotripsy, percutaneous
      nephrolithotomy, and ureteroscopic lithotripsy obviate the need for open surgery
      in essentially all instances.

PMID- 9623618
TI  - Determination of serum creatinine prior to iodinated contrast media: is it
      necessary in all patients?
AB  - The risk of contrast-associated nephrotoxicity (CAN) is increased in the presence
      of preexisting renal disease. Although routine determination of serum creatinine
      (Cr) prior to imaging studies is the traditional method of assessing renal
      function, it is a costly and time-consuming practice. The purpose of this study
      was to investigate whether a patient survey could identify patients with a high
      likelihood of having normal Cr values and who, therefore, did not require serum
      testing. A survey was administered to 673 consecutive adult patients who were
      scheduled for contrast-enhanced computed tomography. Survey questions were
      designed to elicit a history of renal disorders as well as additional risk
      factors for CAN. Each patient had a Cr level determined within 48 hours prior to
      the injection of iodinated contrast media. Cr levels were assessed in the
      patients who gave negative responses to all survey questions. The degree to which
      positive responses to each survey question predicted elevated Cr levels was
      determined using the odds ratio (OR). Among the 673 respondents, 577 (85%) had
      normal Cr values (< or =1.3 mg/dL for women and < or =1.4 mg/dL for men).
      Completely negative responses to the questionnaire occurred in 191 (28%) of 673
      of respondents, and 176 (92%) of these 191 had normal Cr values. A Cr cutoff
      value of 1.7 mg/dL is used in our department, i.e., patients with Cr values >1.7
      mg/dL usually do not receive iodinated contrast media. Using this Cr cutoff
      value, 189 (99%) of 191 patients with negative responses had Cr values less than
      or equal to the cutoff value. The survey questions most strongly associated with
      elevated Cr values pertained to preexisting renal disease (OR 13.6), proteinuria
      (OR 8.7), prior kidney surgery (OR 8.1), hypertension (OR 5.4), gout (OR 4.6),
      and diabetes (OR 3.2). If the survey had been limited to these six questions,
      completely negative responses would have occurred in 450 (67%) of 673, 424 (94%)
      of these 450 would have normal Cr values, and 446 (99%) of 450 would have had Cr
      values at or below the 1.7 mg/dL cutoff for iodinated contrast. A completely
      negative response to a simple (six question) patient survey prior to iodinated
      contrast administration can identify a significant fraction of patients with
      normal Cr levels. Use of this survey could reduce by 67% the number of patients
      undergoing routine Cr determinations prior to imaging studies. This could reduce
      costs, decrease delays, and increase patient satisfaction associated with imaging
      studies.

PMID- 9623619
TI  - Penile enlargement surgery.
AB  - Aesthetic surgery to improve the appearance of the penis, scrotum, and pubic
      region has successfully evolved. Penile lengthening is performed by releasing the
      suspensory ligament of the penis followed by use of penile weights. Girth is
      increased by wrapping a dermal-fat graft around the penile circumference. The
      choice of surgery is determined by the patient's anatomy and desires.

PMID- 9623620
TI  - Ureteroscopic retrograde endopyelotomy.
AB  - With improvements in technology, we continue to seek new surgical techniques to
      approach old surgical issues. Antegrade percutaneous endopyelotomy has become the
      most common first-line approach to treatment of ureteropelvic junction
      obstruction, however, it is now possible to treat this condition successfully
      through a retrograde ureteroscopic approach. By combining the latest small
      ureteroscopes with the technology of endoluminal ultrasound, it is possible to
      treat this disease in a single setting without the complications of ureteral
      strictures or significant postoperative hemorrhage, thereby eliminating the need
      for a nephrostomy tube and dramatically reducing the morbidity of the procedure.

PMID- 9623621
TI  - Transverse preputial flap for ventral penile skin coverage in hypospadias
      surgery.
AB  - A dartos-based transverse skin flap for ventral penile skin coverage is used as
      an adjunct to hypospadias surgery. The technique is simple and reliable. After
      completing the primary repair of the penis, the ventral skin defect is assessed.
      A dartos pedicle is developed, and the flap of dorsal penile skin is transferred
      ventrally along either side of the shaft. To date, 63 boys (ages 6 to 78 months)
      have undergone this type of penile skin reconstruction. Our transverse preputial
      flap has been used as an adjunct to hypospadias repair (28 boys), correction of
      chordee (26 boys), and release of concealed penis (9 boys). During a follow-up
      period of 6 to 74 months, 52 patients (83%) had a favorable cosmetic result. One
      patient experienced a significant loss of epithelium in the early postoperative
      course. Another patient developed a moderate penile torsion, which required
      subsequent revision of the repair. Two patients developed moderate scar
      indentations of the repair. Seven patients demonstrated a moderate redundancy of
      the flap with time. The transverse preputial flap is a reliable and cosmetically
      superior alternative to ventral skin coverage in hypospadias surgery, repair of
      chordee, and in the release of concealed penis.

PMID- 9623622
TI  - Ice-water test in the urodynamic evaluation of spinal cord injured patients.
AB  - The purpose of this study was to determine the clinical utility of the ice-water
      test (IWT) during urodynamic evaluation in spinal cord injured (SCI) patients.
      Thirty-two suprasacral SCI patients with documented detrusor hyperreflexia (DH)
      underwent urodynamic study and IWT. Fifteen patients had repeated testing 2 weeks
      later. The IWT was performed with the patient in the supine position; 100 mL of
      sterile saline water at 4-8 degrees C was injected manually. If cystometric
      capacity was <200 mL, a volume of about 50% of the individual cystometric bladder
      capacity was used. The cold fluid was left within the bladder for 3 minutes. The
      test was considered positive if an involuntary bladder contraction > or =15 cm
      H2O was registered. All patients with cervical or thoracic level SCI had DH,
      which had 100% test-retest reproducibility on urodynamics. Seventy-two percent of
      patients with DH had a positive IWT and 28% had a negative IWT. IWT (same volume,
      2 weeks later) in 4 (27%) of the 15 repeated tests gave different responses.
      Autonomic hyperreflexia, manifested as systolic blood pressure increase > or =50
      mm Hg within 3 minutes of ice-water instillation, occurred in 16 (57%) of 28
      patients with lesions above T7. In SCI patients, the IWT did not contribute to
      their management because of the insensitivity and nonspecificity. Autonomic
      hyperreflexia can occur during evaluation. The IWT did not influence clinical
      management in this group of SCI patients.

PMID- 9623623
TI  - Ureteroscopic treatment of symptomatic caliceal diverticular calculi.
AB  - Renal calculi that reside in caliceal diverticula are difficult to treat.
      Numerous treatment modalities have been used, including extracorporeal shock wave
      lithotripsy, laparoscopy, and percutaneous treatment. All therapies directed at
      fragmenting the stones are limited by the ability of these fragments to pass
      through the narrow diverticular neck. More recently, the retrograde approach
      using small-caliber flexible ureteroscopes has been applied successfully in the
      treatment of diverticular calculi. A description of our retrograde technique is
      presented. The ultimate success of this technique is dependent upon familiarity
      with the basic principles of ureteroscopy and successful clearance of stone
      fragments from the diverticulum.

PMID- 9623624
TI  - Case no. 1. Pott's disease with a large right psoas abscess.

PMID- 9623625
TI  - Case no. 2. Poor visualization of the left kidney--further clinical or
      radiographic staging is indicated.

PMID- 9623626
TI  - Case no. 3. Nonfunctional left kidney with calcified renal cysts from an
      autonephrectomized tuberculosis kidney.

PMID- 9623627
TI  - Case no. 4. Complex benign renal cysts with hemorrhage.

PMID- 9623628
TI  - Transperineal radiofrequency interstitial tumor ablation (RITA) of the prostate.
AB  - The purpose of this study was to investigate the safety and feasibility of
      radiofrequency interstitial tumor ablation (RITA) in localized prostate cancer
      (PCa) and to assess the predictability of the lesions obtained. In 10 patients
      with localized PCa (mean age 70.4 years), a total of 21 marker lesions were
      induced under general (n = 3), spinal (n = 4), or local anesthesia only (n = 3).
      Radiofrequency energy was delivered transperineally under transrectal ultrasound
      (TRUS) guidance. Radical prostatectomy was performed in all patients 1-7 days
      after RITA. The findings of intraoperative TRUS and histologic examination of the
      specimen were correlated. Lesions 2 x 2 x 2 cm were targeted. Postoperatively,
      patients were catheterized for an average of 1.8 days (range 1-3). Average lesion
      diameters defined by coagulative necrosis at histologic examination were 2.20 +/-
      0.23 x 2.10 +/- 0.31 x 2.38 +/- 0.14 cm (average volume 5.86 +/- 1.63 cm3).
      Lesions were well defined and did not extend beyond the prostatic capsule. No
      complications (e.g., rectal wall injury) were noted. RITA-induced lesions were
      safe, feasible, technically simple, and resulted in lesions well predictable in
      size and location. On histologic examination, well-defined areas of coagulative
      necrosis were documented. No damage to the periprostatic tissue was noted. The
      procedure can be performed with spinal or local anesthesia only.

PMID- 9623629
TI  - Somatostatin at low doses stimulates growth hormone release from intact cultures
      of porcine pituitary cells.
AB  - Somatostatin (SRIF) is the primary inhibitory factor in the control of growth
      hormone (GH) release from somatotropes. This concept emerged from studies based
      mainly on the rat and human model. However, recent data suggest that the role of
      SRIF in the regulation of pituitary GH release might be different in other
      species such as the pig. Thus, in previous studies, we have demonstrated a dual
      (stimulatory/inhibitory) effect of SRIF on GH secretion in vitro in two porcine
      somatotrope subpopulations. In the present study, we have investigated whether
      SRIF can act as a GH-releasing factor in intact cultures of porcine somatotropes.
      To this end, both dose-related effects of SRIF on basal GH release and its
      effects on GH-releasing factor (GRF-)stimulated GH secretion were evaluated in
      monolayer cultures of porcine pituitary cells. SRIF did not affect basal
      secretion at the highest doses tested (10(-5), 10(-7), and 10(-9) M), whereas it
      induced a significant increase in GH secretion when applied at low doses (10(
      11), 10(-13), and 10(-15) M). High-dose (10(-7) M) SRIF significantly reduced GRF
      induced GH secretion, an effect that was absent at the lowest dose (10(-15) M) of
      the peptide tested. These results confirm the dual role af SRIF on GH secretion
      from porcine somatotropes, and demonstrate that SRIF, at low doses, can act as a
      true GH-releasing factor.

PMID- 9623630
TI  - Endotoxin modulates arachidonic acid-induced glycogenolysis in the perfused rat
      liver.
AB  - Effects of endotoxin on arachidonic acid (AA)-induced hepatic glycogenolysis were
      examined in perfused rat liver. In normal rat liver, infusion of AA increased
      oxygen consumption and glucose production concurrently. In rats injected with
      lipopolysaccharide (LPS) 6 h before, AA increased glucose production but
      suppressed oxygen consumption. The changes in LPS-injected rat were abolished by
      a thromboxane (Tx) A2 receptor antagonist. The release of Tx B2 by AA increased
      after LPS-injection. These results suggest that priming of hepatic macrophage by
      endotoxin in vivo enhances Tx synthesis, resulting in modulating hepatic
      glycogenolysis.

PMID- 9623631
TI  - Blood flow to the pancreatic islet parenchyma of the Atlantic hagfish (Myxine
      glutinosa).
AB  - The islet organ of the Atlantic hagfish, a cyclostome, phylogenetically is the
      most original islet parenchyma. It is well equipped with blood vessels, but lacks
      nerves. The aim of the present study was to evaluate the relative proportions
      between regional blood flows in these animals with a microsphere technique and
      with laser-Doppler flowmetry. As regards the results obtained in the kidneys,
      gills, and islet organ, the data were essentially the same found using both
      methods. Approximately 20% of the injected microspheres were found in the
      kidneys; when corrected for weight, the gill bodies and the islet organ were also
      found to have the same blood perfusion. The blood flow to the brain and that of
      the gut and the liver were only approximately 30% and 10%, respectively, of that
      to the kidney. Topical application of the nitric oxide donor, sodium
      nitroprusside failed to affect the islet blood flow. Apart from this observation,
      this non-innervated "primitive" islet parenchyma did not differ from that of the
      amply innervated mammalian islets with regard to their high basal blood
      perfusion.

PMID- 9623632
TI  - Influence of paroxetine, branched-chain amino acids and tyrosine on
      neuroendocrine system responses and fatigue in humans.
AB  - Effects of a serotonin re-uptake inhibitor and oral amino acid supplementations
      on physical and mental performance as well as neuroendocrine variables were
      investigated. 10 male subjects cycled in four trials until exhaustion.
      Participants ingested a placebo in trial (T) I, 20 mg paroxetine in T II, 21 g
      branched-chain amino acids (BCAA) in T III and 20g tyrosine (TYR) in T IV. Heart
      rate, capillary lactate, plasma insulin, free fatty acids, glucose, serotonin and
      beta-endorphin did not differ in trials. Plasma ammonia increments during
      exercise were higher in T III. Plasma BCAA in T III and plasma TYR in T IV were
      increased after 30 min of exercise according to the supplemented substances. In
      contrast to all other trials, the ratio of plasma free TRP/BCAA did not increase
      in T III. Plasma TYR/BCAA was augmented in T IV and decreased in T III after 30
      min of exercise, whereas it did not change in T I and II. Plasma prolactin (PRL),
      growth hormone, cortisol, adrenocorticotropic hormone, norepinephrine and
      epinephrine increased during all trials. Plasma PRL increments were higher in T
      IV. Exhaustion was reached earlier in T II. No significant differences were found
      between other trials. Drive during psychometric testing subsequent to exercise
      was improved in T III and IV. The results indicate that fatigue during endurance
      exercise was increased by pharmacological augmentation of the brain serotonergic
      activity. However, a reduction of 5-HT synthesis via BCAA supplementation did not
      affect physical fatigue. TYR administration did not alter physical performance
      either although plasma PRL increments suggest that changes in the monoaminergic
      system were induced. Precaution is necessary before assuming an ergogenic value
      of amino acids.

PMID- 9623633
TI  - A high-sucrose diet alters the lipid composition and fluidity of liver sinusoidal
      membranes.
AB  - Impaired insulin suppression of hepatic glucose production and accumulation of
      hepatic triglycerides occur after 1 week on a high-sucrose diet. The purpose of
      this study was to ascertain whether changes in structural lipids, fatty acid
      composition and/or fluidity occur after 1 week on a high-sucrose diet, and
      therefore might contribute to the sucrose-induced impairment in hepatic glucose
      metabolism. Male Wistar rats (n=28) were fed a purified high starch (68% of
      energy) diet for a 2-week baseline period. Fourteen animals were then switched to
      a high sucrose (68% of energy) diet for 1 (n=7) or 5 (n=7) weeks. Analyses were
      performed on liver sinusoidal membranes (due to this membrane's involvement in
      nutrient transport) from overnight fasted rats. The degree of saturation of
      sinusoidal membrane phospholipids and liver triglyceride fatty acids was
      significantly greater in sucrose vs. starch at 1 and 5 weeks. This resulted in
      significantly lower sinusoidal membrane fluidity at 1 and 5 weeks in the sucrose
      group. In contrast, hepatic sinusoidal membrane cholesterol content (0.60+/-0.05
      vs. 0.42+/-0.04 micromol/mg protein) and the cholesterol to phospholipid molar
      ratio (0.66+/-0.04 vs. 0.50+/-0.03) were significantly greater in sucrose vs.
      starch animals at 5 weeks only. Minimal differences were observed in individual
      phospholipid species between groups. These data suggest that changes in fatty
      acid composition and fluidity may contribute to the development of sucrose
      induced hepatic insulin resistance.

PMID- 9623634
TI  - Stimulatory effect of insulin on calcitonin secretion.
AB  - Infusion of insulin directly into thyroid arterial blood perfusing the surgically
      isolated in situ pig thyroid gland produced an increase in the secretion rate of
      calcitonin (CT) measured by immunoassay in thyroid venous effluent blood. Insulin
      in concentrations ranging from approximately 1 to 400 ng/ml produced a maximal
      stimulation of 4-5 fold. The stimulatory effect of insulin on CT could not be
      duplicated by infusion of either IGF-I or amylin. Specific binding of
      radiolabeled insulin was demonstrated using isolated pig thyroid plasma membranes
      and both rat (6-23) and human (TT) medullary thyroid carcinoma C-cells. Increased
      CT release was observed from C-cells exposed to a high concentration of insulin.
      The administration of glucose iv to pigs in order to stimulate secretion of
      endogenous insulin produced an increase in circulating insulin, which was
      accompanied by an increase in the secretion of CT. The results show that insulin,
      delivered directly to the pig thyroid gland, can stimulate CT release. The in
      vitro binding and secretion studies indicate that C-cells can bind insulin and
      respond with an increase in CT secretion, and the iv glucose experiments suggest
      that endogenous insulin is capable of stimulating CT secretion. The findings
      imply that insulin is capable of acting as a CT secretagogue and suggest that
      changes in CT secretion may accompany altered states of insulin production such
      as diabetes or insulin-secreting tumors.

PMID- 9623635
TI  - Plasma amylin immunoreactivity and insulin resistance in insulin resistant
      relatives of patients with non-insulin-dependent diabetes mellitus.
AB  - To explore the potential relationship between concentrations of circulating
      amylin and the insulin resistance observed in first-degree relatives of patients
      with non-insulin-dependent-diabetes mellitus (NIDDM), we studied 40 relatives
      compared to 35 matched controls. Two newly developed immunoassays that measure
      either non-glycosylated or total amylin were applied. All subjects were examined
      by an oral glucose tolerance test (OGTT) and by a hyperinsulinemic euglycemic
      clamp (insulin infusion: 0.6 mU/kg/min). Glucose tolerance was normal in all, but
      insulin-stimulated glucose uptake (Rd) was diminished in the relatives (p <
      0.001). Area under the curves (AUCs) during OGTT for plasma glucose (p < 0.01)
      and serum insulin (p=0.08), but not for plasma total and non-glycosylated amylin,
      were higher in relatives versus controls. In both groups, inverse correlations
      were found between Rd and AUC for plasma total and non-glycosylated amylin (p
      [all]<0.05). However, in multiple linear regression analyses, plasma total and
      non-glycosylated amylin failed to influence Rd independent of serum insulin and
      family history-of NIDDM. In conclusion, this study demonstrated inverse
      correlations between Rd and circulating concentrations of plasma total and non
      glycosylated amylin in relatives and matched controls. These data, however, do
      not support the hypothesis that physiological amylin concentration are a major
      importance for the insulin resistance in relatives of NIDDM patients.

PMID- 9623636
TI  - Insulin-like growth factor-binding protein-3 (IGFBP-3) but not insulin-like
      growth factor-I (IGF-I) remains elevated in euthyroid TSH-suppressed Graves'
      disease.
AB  - Thyroid hormones have been shown to be involved in the regulation of insulin-like
      growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) expression. This is a
      cross-sectional study to look at the effects of thyroid hormone status on the
      circulating levels of IGF-I and IGFBP-3 in a group of 127 patients, aged 20-80
      years, who were hyperthyroid, hypothyroid, rendered euthyroid and clinically
      euthyroid with normal free thyroxine (fT4), but suppressed thyroid stimulating
      hormone (TSH) levels. TSH was measured by the IMx (Abbott) ultrasensitive assay,
      while radioimmunoassays for total T3 and T4 were performed using kits from ICN,
      USA; fT4 and fT3 using kits from DPC USA; IGF-I and IGFBP-3 using kits from
      Nichols Institute Diagnostics B.V., Netherlands. Differences in the levels of IGF
      I between the 4 groups of patients were significant only in the patients aged 20
      40. Mean (+/-SEM) IGF-I levels of hypothyroid patients (169+/-19ng/ml) was
      significantly lower than hyperthyroid (315+/-26 ng/ml, p=0.003), euthyroid
      patients (241+/-19 ng/ml, p=0.002) and patients with suppressed TSH (308+/-29
      ng/ml, p=0.02). The IGF-I levels of the hyperthyroid and suppressed TSH patients
      were, however, comparable to age-matched normal subjects (281+/-86 ng/ml).
      Although there was no difference in mean IGFBP-3 levels between the 4 groups of
      patients, the levels in the patients aged 20-40 with hyperthyroidism (3.7+/-0.9
      microg/ml) and suppressed TSH (3.9+/-1.2 microg/ml) were significantly higher
      (p=0.02) than age-matched normal subjects (3.1+/-0.8 microg/ml). The IGF-I levels
      of the thyroid patients aged 20-40 showed significant negative correlation to TSH
      and positive correlations to the thyroid hormones. Hence, whilst low IGF-I is
      associated with hypothyroidism, high IGFBP-3 is associated with hyperthyroidism.
      Our finding that IGFBP-3 remained significantly elevated in patients with
      suppressed TSH but normalised fT4 and fT3 is important as it suggests a prolonged
      tissue effect of thyroid hormones on IFGBP-3. As such patients have been shown to
      have higher risk for atrial fibrillation, the significance and possible role of
      IGFBP-3 in these conditions should be further elucidated in future studies.

PMID- 9623637
TI  - The effects of thyroid status on serum apolipoprotein A-I-containing lipoprotein
      particles.
AB  - Alterations of lipid profile are a well-known phenomenon in thyroid dysfunction.
      However, little is known about the influence of thyroid hormone on Lp A-I and LpA
      I:A-II particles. We have, therefore, studied LpA-I and LpAI:A-II concentrations
      in a group of 20 patients with hyperthyroidism and in a group of 15 patients with
      hypothyroidism before and one month after attainment of euthyroidism. In
      hypothyroid patients, LDL-cholesterol and apo B concentrations decrease
      significantly after L-T4 replacement treatment (from 4.49+/-2.51 to 2.76+/-0.70
      mmol/ L, P=0.036 and from 89.4+/-16.1 to 78.3+/-13.3 mg/dL, P=0.05,
      respectively), whereas no significant change was observed in the total
      cholesterol, HDL-C, LpA-I, LpA-I:A-II and apo A-I concentrations. In hyperthyroid
      patients, total cholesterol (from 3.58+/-0.72 to 4.74+/-1.39mmol/L, P=0.0025),
      HDL-C (from 1.19+/-0.23 to 1.41+/-0.27mmol/L, P=0.0084), LDL-C (from 1.83+/-0.69
      to 2.96+/-1.20 mmol/l, P=0.0025), apo A-I (from 85.6+/-12.5 to 91.7+/-18.1 mg/dL,
      P=0.05) and apo B (from 52.7+/-8.2 to 65.6+/-16.5 mg/dL, P=0.0013) increased
      after restoration of euthyroidism while triglycerides, LpA-I and LpA-I: A-II
      concentrations were unchanged. LpA-I and LpA-I:A-II concentrations were not
      related to thyroid hormones in both groups. Our study suggests that LpA-I and LpA
      I:A-II particles are not under the direct control of thyroid hormones.

PMID- 9623639
TI  - Allopregnanolone in women with premenstrual syndrome.
AB  - 5Alpha-reduced metabolites of progesterone, especially 3alpha-hydroxy-5alpha
      pregnan-20-one (allopregnanolone) are now listed to neurosteroids. Their
      anesthetic properties can be explained by their allosteric interaction with
      GABA(A) receptors. A woman's organism is provided with an abundance of
      progesterone during the luteal phase of the menstrual cycle and its level falls
      down sharply with the first day of menses. The level of allopregnanolone follows
      that of progesterone. Many women suffer from so called premenstrual syndrome
      (PMS) during the luteal phase. In this study we have determined allopregnanolone
      and progesterone levels and their ratios in order to assess the over-all activity
      of C21-steroid 5alpha-reductase in these patients and in controls. Significantly
      lower levels of both progesterone and allopregnanolone than in controls have been
      found in PMS patients in the follicular phase only.

PMID- 9623638
TI  - Effects of i.v. insulin bolus on urinary calcium and oxalate excretion in healthy
      subjects.
AB  - Oral glucose load increases urinary excretion of calcium (Ca) and oxalate.
      Although this increase in calciuria is commonly ascribed to insulin, the role of
      glucose on Ca excretion remains unclear. In order to assess the role of glucose
      changes on calciuric response to insulin and oxalate excretion, hypoglycemia
      induced by insulin (hypo) and hyperglycemia induced by oral glucose load (hyper)
      were studied in 7 healthy subjects on two separate days. As expected, glycemia
      dropped in hypo (-70%, p<0.001) and increased in hyper (+67%, p<0.001). Calciuria
      increased on the two days,+205%, p<0.001 (hypo) vs + 43%, p < 0.05 (hyper) as a
      result of both a rise in calcium filtered load (FCa) and a decrease in tubular
      reabsorption of calcium (TRCa). While the increase in FCa was similar in the two
      situations, the higher increased calciuria in hypo (p<0.01) was linked to a
      deeper decrease in TRCa, - 2.1 % (hypo) vs - 1.4% (hyper), p < 0.01. Although the
      estimated amounts of insulin were similar in the two situations, the insulin
      kinetics were different. Thus, after insulin injection, the putative role of the
      high initial insulin spike in triggering the increase in calciuria cannot be
      ruled out. The deeper decrease in TRCa (hypo) was also likely due to both
      hypoglycemia and changes in counter-regulation hormones. In conclusion, calciuria
      increased after either hypo or hyperglycemia and the higher increase in calciuria
      observed in hypo was subsequent to a deeper decrease in tubular Ca reabsorption.
      Oxaluria did not change in hypo, while it increased in hyper.

PMID- 9623640
TI  - Torsion measurement of catheters using polarized light in a single glass fibre.
AB  - Several types of intravascular ultrasound (IVUS) catheters are connected to a
      motor at their proximal end, in order to let the catheter rotate around its
      length axis. However, the rotation of the distal axis tip does not follow exactly
      the rotation of the motor, since the catheter axis is not completely torsion-free
      and friction forces cause the tip to rotate in a shockwise manner. In the case of
      the IVUS catheter, continuous information concerning the exact rotation of the
      crystal is essential for 3D image reconstruction. We developed a simple method of
      measuring the tip rotation continuously, the TOMCAT method, using only a single
      optical fibre glued in a fixed position inside the rotating axis of the IVUS
      catheter, or any rotating axis or catheter in general. Our method does not
      require external electromagnetic fields or the presence of a non-rotating guiding
      catheter. The rotation of the distal tip is related to that of the proximal part
      by transporting polarized light through the fibre. We performed in vitro
      experiments using various types of optical fibres to test the TOMCAT method, and
      conclude that using a specific step-index monomode cylinder-symmetrical optical
      fibre the TOMCAT approach yields accurate results.

PMID- 9623641
TI  - Effects of skeletal muscle anisotropy on human organ dosimetry under 60 Hz
      uniform magnetic field exposure.
AB  - The recent development of anatomically derived high-resolution voxel-based models
      of the human body suitable for electromagnetic modelling, and of effective
      methods for computing the associated induction, has resulted in numerical
      estimates of organ-specific dosimetry for human exposure to low-frequency
      magnetic fields. However, these estimates have used an isotropic conductivity
      model for all body components. More realistic estimates should account for the
      anisotropy of certain tissues, particularly skeletal muscle. In this work, high
      resolution finite-difference computations of induced fields are used to estimate
      the effects of several extremal realizations of skeletal muscle anisotropy on
      field levels in various organs. It is shown that, under the present assumptions
      (anisotropy ratios up to 3.5:1), the resulting dosimetric values can vary by
      factors of between two or three for tissues other than muscle and up to 5.4 for
      muscle, despite the unchanged nature of the conductivity model used for all other
      body components.

PMID- 9623642
TI  - Automatic cell electrorotation measurements: studies of the biological effects of
      low-frequency magnetic fields and of heat shock.
AB  - A computer-aided automatic imaging technique has been developed for measuring the
      electrorotation spectra of up to 256 particles at the same time. This offers
      advantages over the conventional manual method, especially when rapidly acquired
      statistical data are necessary in investigations of the response of cells or test
      beads to chemical exposure, for example. We have applied this technique to
      investigate the biological effects of heat shock and low-frequency EM fields
      reported by others for yeast cells. Although heat shock effects were observed, no
      changes of the electrorotational behaviour could be detected after exposing the
      cells to 50 Hz, 8 and 80 microT fields. Although this does not rule out the
      possibility that the cells were influenced by the magnetic fields, it does limit
      the number of possible physicochemical changes that might have occurred to their
      cell walls and membranes.

PMID- 9623643
TI  - Target, purging magnet and electron collector design for scanned high-energy
      photon beams.
AB  - A new method for producing very narrow and intense 50 MV bremsstrahlung beams
      with a half-width as low as 35 mm at a distance of 1 m from the target is
      presented. Such a beam is well suited for intensity modulation using scanned
      photon beams. An algorithm has been developed to minimize the width of the
      bremsstrahlung beam generated in a multilayer target by varying the individual
      layer thicknesses and atomic numbers under given constraints on the total target
      thickness and the mean energy of the transmitted electrons. Under such
      constraints the narrowest possible bremsstrahlung beam is obtained with a target
      composed of layers of monotonically increasing atomic number starting with the
      lowest possible value at the entrance side where the electrons impinge. It is
      also shown that the narrowest photon beam profile is associated with the highest
      possible forward photon yield. To be able to use the optimized target clinically
      it is desirable to be able to collect and stop all the electrons that are
      transmitted through the target. The electrons are most efficiently collected if
      they are kept close together, i.e. by minimizing the multiple scatter of the
      electrons and consequently the half-width of the generated bremsstrahlung beam.
      This is achieved by a thin low-atomic-number target. A dedicated electron stopper
      has been developed and integrated with the purging magnet. When the electron
      stopper is combined with a purging magnet, a primary photon collimator and a
      multileaf collimator, almost all of the transmitted electrons and their
      associated bremsstrahlung contamination can effectively be collected. The narrow
      photon beams from thin low-atomic-number targets have the additional advantage of
      producing the hardest and most penetrative photon spectrum possible, which is
      ideal for treating large deep-seated tumours.

PMID- 9623644
TI  - An investigation into the dosimetry of a nine-field tomotherapy irradiation using
      BANG-gel dosimetry.
AB  - BANG-gel dosimetry offers the potential for measuring the dose delivered by a
      radiotherapy treatment technique, in three dimensions, with high spatial
      resolution and good accuracy. The ability to measure comprehensively a 3D dose
      distribution is a major advantage of the gel dosimeter over conventional planar
      and point-based dosimeter devices, particularly when applied to the verification
      of complex dose distributions characteristic of intensity-modulated radiotherapy
      (IMRT). In this paper an in-house manufactured BANG-gel dosimeter was applied to
      study the dose distributions of two irradiation experiments for which the
      distributions were known: (i) a dosimetrically simple parallel-opposed
      irradiation, and (ii) a more complex nine-field 'static tomotherapy' intensity
      modulated irradiation delivered with the Nomos MIMiC. The uniform distribution in
      (i) allowed a study of the magnetic resonance (MR) imaging parameters to achieve
      an optimal trade-off between noise and image resolution (optimum image resolution
      for the Siemens 1.5T Vision system was determined to be approximately 0.8 mm2
      with a slice thickness of 2 mm). The spatial uniformity of gel sensitivity to
      radiation was found to depend strongly on the presence of oxygen, which must be
      eliminated for the gel dosimeter to be of use. The gel dosimeter was found to
      agree well with predicted dose distributions and accurately measured the steep
      penumbral fall-off of dose, even after many days, proving its potential for the
      verification of IMRT distributions. In the nine-field IMRT delivery (ii) the
      predicted dose was computed by both an in-house 'component-delivery' dose
      algorithm and the Peacock planning-system dose algorithm. Good agreement was
      found between the two algorithms despite the latter's omission of the change in
      penumbral characteristics with aperture-size during delivery, lack of
      inhomogeneity correction and approximate modelling of leaf leakage. These effects
      were found to be small for the problem studied. The predicted distribution agreed
      well with the gel-measured distribution at medium and high doses (50-90% isodose
      lines) although differences of up to 10% were observed at lower doses (30%
      isodose line). The gel dosimeter was found to have the potential to verify IMRT
      distributions but required considerable care to achieve accurate results.
      Attention was required to achieve uniformity of gel sensitivity (to prevent
      oxygen contamination), and in the calibration process.

PMID- 9623645
TI  - Investigation and modelling of the surface dose from linear accelerator produced
      6 and 10 MV photon beams.
AB  - The radiation reaction from the surface dose to a patient's skin is clinically
      important as an indicator of tolerance to treatment and is frequently the most
      visible side-effect from external beam radiotherapy. To quantify surface dose,
      its build-up was investigated in a solid water phantom over a range of field
      sizes, source to skin distances, wedge angles and beam shaping conditions. These
      data were analysed and used to produce an empirical model of the effect of these
      factors which predicted surface dose to within 5% under test conditions. The
      effects of changing treatment techniques was investigated by comparing fixed to
      dynamic wedges, and multileaf collimator (MLC) with alloy blocks. It was found
      that the MLC reduced the surface dose relative to alloy blocks but that dynamic
      wedges made no change relative to open fields. Fixed wedges reduced the relative
      surface dose as a consequence of beam hardening. It is hoped that routine
      clinical use of the model to calculate skin dose will increase awareness of
      situations in which the skin sparing effect of modern linear accelerators may be
      compromised.

PMID- 9623646
TI  - A position-sensitive superheated emulsion chamber for three-dimensional photon
      dosimetry.
AB  - A position-sensitive detector chamber is introduced for the three-dimensional
      (3D) dosimetry of photon-emitting brachytherapy sources. The detector is based on
      an extremely fine suspension of monochloropentafluoroethane droplets emulsified
      in a gel. The droplets are highly superheated at room temperature and their
      evaporation can be triggered by photon interactions, leading to the formation of
      microscopic bubbles. Thus, when photon-emitting brachytherapy sources are
      inserted into the detector, bubble distributions form around them, enabling
      visualization of the radiation field. The tissue-equivalent emulsifier gel is
      highly viscous and keeps the bubbles immobilized at the location of their
      formation. Bubbles can then be imaged by nuclear magnetic resonance or optical
      scanning techniques. After the imaging, the detector can be pressurized in order
      to recondense the bubbles to the liquid phase. In a few minutes, the device is
      annealed and ready to be used again for repeated measurements improving the
      counting statistics. The photon sensitivity of the monochloropentafluoroethane
      droplets was determined with highly filtered, quasi-monochromatic x-ray beams and
      radionuclide gamma sources. The air-kerma response presents a broad maximum at
      low energies, due to the relatively high effective atomic number of the
      halocarbon molecule. A prototype chamber was built and successfully tested:
      bubble distributions deriving from the insertion of a 125I source were imaged by
      means of a slice-selective 3D gradient-echo technique. These experiments confirm
      the potential and viability of this new approach to 3D photon dosimetry.

PMID- 9623647
TI  - Intensity modulation with electrons: calculations, measurements and clinical
      applications.
AB  - Intensity modulation of electron beams is one step towards truly conformal
      therapy. This can be realized with the MM50 racetrack microtron that utilizes a
      scanning beam technique. By adjusting the scan pattern it is possible to obtain
      arbitrary fluence distributions. Since the monitor chambers in the treatment head
      are segmented in both x- and y-directions it is possible to verify the fluence
      distribution to the patient at any time during the treatment. Intensity modulated
      electron beams have been measured with film and a plane parallel chamber and
      compared with calculations. The calculations were based on a pencil beam method.
      An intensity distribution at the multileaf collimator (MLC) level was calculated
      by superposition of measured pencil beams over scan patterns. By convolving this
      distribution with a Gaussian pencil beam, which has propagated from the MLC to
      the isocentre, a fluence distribution at isocentre level was obtained. The
      agreement between calculations and measurements was within 2% in dose or 1 mm in
      distance in the penumbra zones. A standard set of intensity modulated electron
      beams has been developed. These beams have been implemented in a treatment
      planning system and are used for manual optimization. A clinical example
      (prostate) of such an application is presented and compared with a standard
      irradiation technique.

PMID- 9623648
TI  - Leaf trajectory calculation for dynamic multileaf collimation to realize
      optimized fluence profiles.
AB  - An algorithm for the calculation of the required leaf trajectories to generate
      optimized intensity modulated beam profiles by means of dynamic multileaf
      collimation is presented. This algorithm iteratively accounts for leaf
      transmission and collimator scatter and fully avoids tongue-and-groove
      underdosage effects. Tests on a large number of intensity modulated fields show
      that only a limited number of iterations, generally less than 10, are necessary
      to minimize the differences between optimized and realized fluence profiles. To
      assess the accuracy of the algorithm in combination with the dose calculation
      algorithm of the Cadplan 3D treatment planning system, predicted absolute dose
      distributions for optimized fluence profiles were compared with dose
      distributions measured on the MM50 Racetrack Microtron and resulting from the
      calculated leaf trajectories. Both theoretical and clinical cases yield an
      agreement within 2%, or within 2 mm in regions with a high dose gradient, showing
      that the accuracy is adequate for clinical application.

PMID- 9623649
TI  - Scanned intensity modulations for 50 MV photons.
AB  - Optimization of the dose distributions by individual beam compensation is a
      useful tool in conformal radiation therapy. Intensity modulation by
      electromagnetic scanning of a narrow elementary beam allows fast dose delivery
      and causes little change in beam quality compared with other methods, especially
      for high energies such as 50 MV. Intensity modulated beams from the MM50
      accelerator were measured and compared with calculations based on Monte Carlo
      simulations. Good agreement between measurements and calculations were found,
      typically within 1% for central dose profiles. The steepest wedge angle that was
      produced with the scanning beam technique was of 45 degrees or 3.5% cm(-1) for a
      20 cm x 20 cm field, slightly varying with depth. The elementary 50 MV photon
      'pencil beam' for a full range, high-z bremsstrahlung target, is a wide dose
      distribution at 10 cm depth in water which limits the modulation gradient and
      hence the complexity of the modulation by the scanning of a photon pencil beam
      only. Scanned wedge beam distributions were modelled in the treatment planning
      system and a pelvic treatment with three fields was used to illustrate a clinical
      application. The resulting dose volume data were compared for different radiation
      qualities but with similar beam portals. 'Energy modulation' by field matching
      with lower photon energies was performed to sharpen the penumbra towards organs
      at risk.

PMID- 9623650
TI  - Comparison of temperature distributions in interstitial hyperthermia: experiments
      in bovine tongues versus generic simulations.
AB  - Temperature distributions resulting from hyperthermia treatments on isolated
      perfused bovine tongues were compared with simulations by a treatment planning
      system. The aim was to test whether the discrete vessel model used for the
      treatment planning is able to predict correct generic temperature distributions.
      Tongues were heated with the multielectrode current source interstitial
      hyperthermia treatment (MECS IHT) system, while the steady-state temperature
      distribution was mapped by scanning 10 thermocouples along paths perpendicular to
      the interstitial implant. For simulations a tongue was defined with generic
      discrete vasculature and an electrode implant analogue to the experiments. To
      model vascular generations not described discretely, a local heatsink was
      implemented at the end of each terminating branch. The discretely modelled
      vasculature showed itself on the temperature distributions in two ways.
      Individual vessels caused very local, sharp wells in the tracked temperature
      profiles. In the presence of large vessels a collective behaviour was also seen,
      i.e. a regional lowering of temperature. Both phenomena can be recognized in the
      experimentally obtained temperature distributions too. Predicting correct generic
      temperature distributions is feasible with the discrete vessel model used.

PMID- 9623651
TI  - Nonlinear reconstruction constrained by image properties in electrical impedance
      tomography.
AB  - It is proposed that image quality, for example the degree of roughness, in
      electrical impedance tomography is the essential measure required to regularize
      nonlinear reconstruction. Most previously published work has addressed
      efficiency, stabilization and speed of reconstruction and has overlooked the
      targeted image qualities. The measure of quality adopted is the mean square
      gradient of the logarithm of resistivity which, in combination with the chi2
      statistic as a measure of the fit to the data, is minimized by iteration until
      convergence to a stable image is achieved. This penalty function is invariant to
      the scale of the resistivity and to the interchange of resistivity and
      conductivity. The algorithm is tested on computer simulated data and on
      measurements from a cylindrical tank of electrolyte. The results demonstrate the
      increased image definition that it would be possible to achieve as data
      acquisition systems are improved. The images show how a reduction in resolution
      can be traded for reduced noise artefacts, by selecting an appropriate target
      chi2.

PMID- 9623652
TI  - The application of infrared spectroscopy to breath CO2 isotope ratio measurements
      and the risk of spurious results.
AB  - Stable CO2 isotope breath tests are established as a valuable tool in diagnostic
      and investigative medicine with the potential to become more prominent in the
      future. However, their development and widespread clinical use is limited by the
      requirement of isotope ratio mass spectroscopic analysis. To overcome this
      restriction alternative analytical techniques have been developed; the most
      promising, offering relative simplicity and lower costs, are those instruments
      using infrared spectroscopy. Clinical investigations using such instruments show
      them to perform well but very little attention has been given to the possibility
      of interference from the infrared absorption spectrum of other compounds in the
      breath. To provide an unambiguous answer to this concern we have analysed
      literature on over 200 detected breath compounds and their infrared absorption
      spectra to identify any absorption bands coincident with the nu3 absorption band
      of CO2. It was found that only five breath trace compounds possess coincident
      fundamental absorption bands, none of which pose the risk of spurious results. We
      conclude that the 13C16O2/12C16O2 ratio can confidently be measured for isotopic
      breath tests using an infrared spectrometer, the position of the nu3 absorption
      band of CO2 in the infrared spectrum precluding any discernible risk of spurious
      measurements due to coincidental absorption bands.

PMID- 9623653
TI  - Tissue motion assessment from 3D echographic speckle tracking.
AB  - The potential of ultrasonic image speckle tracking to characterize tissue
      dynamics has been illustrated and validated elsewhere. In this paper we wish to
      extend this speckle tracking methodology to 3D. To investigate the feasibility of
      such an approach we first model the image formation process and simulate the 3D
      speckle motion inherent to tissue linear transformations (translation, rotation
      and deformation). It is shown that tissue axial rotation and translation are
      perfectly correlated with the tissue speckle motion while tissue deformation and
      non-axial rotations corrupt the speckle pattern with a motion-induced noise and
      are therefore more difficult to track when large motions are concerned.
      Furthermore, in the framework of our model, our results indicate that short
      ultrasound pulses with low frequencies and small beamwidths are more desirable
      for a speckle tracking methodology. The feasibility of speckle tracking is
      illustrated with an optical flow algorithm. A theoretical study of the
      correlation between various linear transformations of the tissue and the
      corresponding ultrasonic speckle motions is also performed.

PMID- 9623654
TI  - Registration of MR and SPECT without using external fiducial markers.
AB  - The aim of our work is to present, test and validate an automated registration
      method used for matching brain SPECT scans with corresponding MR scans. The
      method was applied on a data set consisting of ten brain IDEX SPECT scans and ten
      T1- and T2-weighted MR scans of the same subjects. Of two subjects a CT scan was
      also made. (Semi-) automated algorithms were used to extract the brain from the
      MR, CT and SPECT images. Next, a surface registration technique called chamfer
      matching was used to match the segmented brains. A perturbation study was
      performed to determine the sensitivity of the matching results to the choice of
      the starting values. Furthermore, the SPECT segmentation threshold was varied to
      study its effect on the resulting parameters and a comparison between the use of
      MR T1- and T2-weighted images was made. Finally, the two sets of CT scans were
      used to estimate the accuracy by matching MR to CT and comparing the MR-SPECT
      match to the SPECT-CT match. The perturbation study showed that for initial
      perturbations up to 6 cm the algorithm fails in less than 4% of the cases. A
      variation of the SPECT segmentation threshold over a realistic range (25%) caused
      an average variation in the optimal match of 0.28 cm vector length. When T2 is
      used instead of T1 the stability of the algorithm is comparable but the results
      are less realistic due the large deformations. Finally, a comparison of the
      direct SPECT-MR match and the indirect match with CT as intermediate yields a
      discrepancy of 0.4 cm vector length. We conclude that the accuracy of our
      automatic matching algorithm for SPECT and MR, in which no external markers were
      used, is comparable to the accuracies reported in the literature for non
      automatic methods or methods based on external markers. The proposed method is
      efficient and insensitive to small variations in SPECT segmentation.

PMID- 9623655
TI  - Evaluation of a cross-validation stopping rule in MLE SPECT reconstruction.
AB  - One of the problems in the routine use of the maximum-likelihood estimator method
      expectation maximization (MLE-EM) algorithm is to decide when the iterative
      process should be stopped. We studied a cross-validation stopping rule to assess
      its usefulness in SPECT. We tested this stopping rule criterion in the MLE-EM
      algorithm without acceleration as well as in two accelerating algorithms, the
      successive substitutions algorithm (SSA) and the additive algorithm (AA).
      Different values of an acceleration factor were tested in SSA and AA. Our results
      from numerical and physical phantoms show that the stopping rule based on the
      cross-validation ratio (CVR) takes into account the similarity of the
      reconstructed image to the ideal image, noise and the contrast of the image. CVR
      yields reconstructed images with balanced values of the figures of merit (FOM)
      employed to assess the image quality. The CVR criterion can be used in the
      original MLE-EM algorithm as well as in SSA and AA. The reconstructed images
      obtained with SSA and AA showed FOM values that were very similar. These results
      were justified by considering AA to be an approximate form of SSA. The range of
      validity for the acceleration factor in SSA and AA was found to be [1, 2]. In
      this range, an inverse function connects the acceleration factor to the number of
      iterations needed to attain prefixed values of FOMs.

PMID- 9623656
TI  - Comparison of finite-difference transport and diffusion calculations for photon
      migration in homogeneous and heterogeneous tissues.
AB  - We analyse the limits of the diffusion approximation to the time-independent
      equation of radiative transfer for homogeneous and heterogeneous biological
      media. Analytical calculations and finite-difference simulations based on
      diffusion theory are compared with discrete-ordinate, finite-difference transport
      calculations. The influence of the ratio of absorption and transport scattering
      coefficient (mu(a)/mu'(s)) on the accuracy of the diffusion approximation are
      quantified and different definitions for the diffusion coefficient, D, are
      discussed. We also address effects caused by void-like heterogeneities in which
      absorption and scattering are very small compared with the surrounding medium.
      Based on results for simple homogeneous and heterogeneous systems, we analyse
      diffusion and transport calculation of light propagation in the human brain. For
      these simulations we convert density maps obtained from magnetic resonance
      imaging (MRI) to optical-parameter maps (mu(a) and mu'(s)) of the brain. We show
      that diffusion theory fails to describe accurately light propagation in highly
      absorbing regions, such as haematoma, and void-like spaces, such as the
      ventricles and the subarachnoid space.

PMID- 9623658
TI  - Angular dependence of resistance in non-invasive electrical measurements of human
      muscle: the tensor model.
AB  - Previous calculations of the angular dependence of the resistance of muscle,
      based on tensorial anisotropy, are in contradiction with recent measurements on
      the intact human thigh. We show that careful treatment of lateral boundaries and
      electrode sizes leads to a reconciliation of the tensor model and the
      experimental observations.

PMID- 9623657
TI  - Detection system for ocular refractive error measurement.
AB  - An automatic and objective system for measuring ocular refractive errors (myopia,
      hyperopia and astigmatism) was developed. The system consists of projecting a
      light target (a ring), using a diode laser (lambda = 850 nm), at the fundus of
      the patient's eye. The light beams scattered from the retina are submitted to an
      optical system and are analysed with regard to their vergence by a CCD detector
      (matrix). This system uses the same basic principle for the projection of beams
      into the tested eye as some commercial refractors, but it is innovative regarding
      the ring-shaped measuring target for the projection system and the detection
      system where a matrix detector provides a wider range of measurement and a less
      complex system for the optical alignment. Also a dedicated electronic circuit was
      not necessary for treating the electronic signals from the detector (as the usual
      refractors do); instead a commercial frame grabber was used and software based on
      the heuristic search technique was developed. All the guiding equations that
      describe the system as well as the image processing procedure are presented in
      detail. Measurements in model eyes and in human eyes are in good agreement with
      retinoscopic measurements and they are also as precise as these kinds of
      measurements require (0.125D and 5 degrees).

PMID- 9623659
TI  - Relations between scatter factor, quality index and attenuation for x-ray beams.
AB  - The relations between the attenuation factor, the normalized phantom scatter
      factor and the quality index are examined using a semiempirical formula for the
      dose on the central axis of an x-ray beam in water. The study is restricted to
      depths and field sizes sufficient for electron equilibrium. The results are
      compared with data in the recent literature. It is concluded that for x-ray beams
      in the energy range 4-25 MV the normalized scatter factors can be calculated from
      the dose-weighted average linear attenuation coefficient in water, determined
      from transmission measurements in a narrow-beam geometry or from the quality
      index.

PMID- 9623660
TI  - An expression for backscatter factors for orthovoltage x-rays.
AB  - Backscatter factors for orthovoltage x-ray beams are fitted with the expression
      BSF = 1 + ms/(s + n), where s is field size and m and n are adjustable
      parameters. The accuracy is better than 0.5%. Good results were also obtained for
      Cs-137 gamma rays at depth 0.12 cm and Co-60 gamma rays at depth 0.5 cm using the
      same expression, which failed, however, for peak scatter factors at high x-ray
      energies.

PMID- 9623661
TI  - Design considerations for the sides of multileaf collimator leaves.
AB  - The use of multileaf collimators (MLCs) in radiation therapy is becoming
      increasingly widespread as more commercial vendors offer them as options on
      medical linear accelerators. In most of the commercially available multileaf
      collimators, the sides of the leaves have a 'tongue and groove' (TG) feature,
      which is necessary for blocking the straight through leakage when the leaves are
      staggered together. The dosimetric effects of the TG design have not been fully
      studied for applications in block replacement or in dynamic intensity modulation.
      This article analytically explains the TG effect by calculating a deficit in
      photon flux when the side of a leaf is exposed. It is shown that the maximum
      photon deficit occurs when the leaf thickness is shared equally by the tongue and
      groove of adjacent leaves. New designs are proposed based on the theoretical
      analysis and improvements of the new design in leakage and the TG effect are
      verified with Monte-Carlo simulations. Measurements of the TG effect on an MLC
      from one manufacturer are also conducted. The results of the measurements confirm
      the analytical explanations of the TG effect.

PMID- 9623662
TI  - High dose behind inhomogeneities during medium-energy x-ray irradiation.
AB  - Medium-energy x-rays from orthovoltage treatment units are used for a variety of
      radiotherapy treatments ranging from cutaneous malignancies in the head and neck
      region to bone metastases. It was the aim of the present study to investigate the
      dose distribution due to secondary electrons close behind inhomogeneities in
      these radiation qualities. The dose was assessed in a solid water phantom using
      three plane-parallel ionization chambers (NE 2532/2, 'Markus' and 'Attix'
      chamber) and sheets of aluminium, copper, zinc, platinum, lead and bone
      equivalent material. The depth dose distribution directly behind the
      inhomogeneity was assessed using sheets of 15 microm thick polyethylene foil. A
      dose increase was found directly behind inhomogeneities of high atomic number
      with a rapid dose fall-off over the first 100 microm. The dose downstream of the
      inhomogeneity was found to increase with increasing beam quality from 120 kVp
      (HVL 2.8 mm Al) to 250 kVp (HVL 2 mm Cu). In the latter the dose was increased
      directly behind lead and platinum sheets by up to a factor of eight compared with
      a solid water depth of similar attenuation. The results of the study demonstrate
      the importance of using appropriate materials if shielding is in contact with the
      patient.

PMID- 9623663
TI  - Comparison of EGS4 and MCNP Monte Carlo codes when calculating radiotherapy depth
      doses.
AB  - The Monte Carlo codes EGS4 and MCNP have been compared when calculating
      radiotherapy depth doses in water. The aims of the work were to study (i) the
      differences between calculated depth doses in water for a range of monoenergetic
      photon energies and (ii) the relative efficiency of the two codes for different
      electron transport energy cut-offs. The depth doses from the two codes agree with
      each other within the statistical uncertainties of the calculations (1-2%). The
      relative depth doses also agree with data tabulated in the British Journal of
      Radiology Supplement 25. A discrepancy in the dose build-up region may by
      attributed to the different electron transport algorithims used by EGS4 and MCNP.
      This discrepancy is considerably reduced when the improved electron transport
      routines are used in the latest (4B) version of MCNP. Timing calculations show
      that EGS4 is at least 50% faster than MCNP for the geometries used in the
      simulations.

PMID- 9623664
TI  - An investigation into the use of carbon fibre for megavoltage radiotherapy
      applications.
AB  - Properties of carbon fibre of relevance to its use for megavoltage radiotherapy
      applications have been investigated. Measurements have been made of the
      percentage transmission and percentage build-up of carbon fibre at energies of 5,
      6 and 8 MV. The results are presented in comparison with those obtained for other
      materials commonly used in radiotherapy: polymethylmethacrylate (PMMA), PETG
      copolyester and expanded polystyrene foam. It was found that carbon fibre has a
      higher percentage transmission and a lower percentage build-up than either PMMA
      or PETG copolyester. It was also found that the build-up due to a combination of
      carbon fibre and 5 cm of polystyrene foam was less than 65% over the energy range
      for which measurements were made, and much lower than that due to PETG
      copolyester. It is thus proposed that carbon fibre is a suitable material from
      which to make devices for use in megavoltage radiotherapy.

PMID- 9623665
TI  - X-ray characterization of breast phantom materials.
AB  - A pulse-height spectroscopic technique is used to measure the linear attenuation
      coefficients of commercially available composite phantom materials designed to
      simulate the attenuation characteristics of breast fat and breast glandular
      tissue. The manufacturers have specified the composition of these materials with
      the goal of matching the linear attenuation coefficients of breast tissues,
      calculated using the mixture rule. Over the energy range 18 to 100 keV,
      measurements from these materials are in close agreement with manufacturers'
      predictions and with previously measured linear attenuation coefficients of
      breast tissue samples.

PMID- 9623666
TI  - The 40K activity of one gram of potassium.

PMID- 9623667
TI  - A new episcopic method for rapid 3-D reconstruction: applications in anatomy and
      embryology.
AB  - The topographic relations of complex structures and the morphogenesis of organ
      systems can only be fully understood in their three-dimensional context. Three
      dimensional (3-D) reconstruction of physically sectioned specimens has become an
      indispensable tool in modern anatomical and embryological research. Teaching also
      makes increasingly use of 3-D representations, in particular in the case of
      embryonic systems that undergo complicated transformations of form and shape. At
      present no cheap and simple technique is available that generates accurate 3-D
      models of sectioned objects. In this study we describe a novel technique that
      rapidly provides faithful 3-D models of sectioned specimens. The images are
      captured directly from the cutting surface of the embedding block after each
      sectioning and "on block" staining step. Automatic image processing generates a
      stack of binary images of the specimen contour. Binary images of internal
      structures are obtained both by automatic segmentation and manual tracing. Since
      these image series are inherently aligned, they can be reconstructed three
      dimensionally without time-consuming alignment procedures. The quality and the
      flexibility of the method are demonstrated by reconstructing three kinds of
      specimens of different histological composition and staining contrast: a 4 mm
      mouse embryo together with several of its inner organs, a cavernous sinus region
      of a human infant, and a segment of a human carotid artery. Very short processing
      times and the faithful representation of complex structural arrangements
      recommend this technique for routine use in morphological research and for
      creating embryologic teaching models or 3-D embryonic staging series.

PMID- 9623668
TI  - Stromal cell structure and relationships in perimedullary spaces of chick embryo
      shaft bones.
AB  - Structure and relationships of stromal cells were studied by light (LM) and
      transmission electron microscopy (TEM) in the perimedullary spaces that form the
      growing cortex of the chick embryo tibia. Observation under LM showed that in all
      perimedullary spaces the interstices between the cells carpeting the bone surface
      and the endothelial lining contain stromal cells surrounded by an amorphous
      matrix. Two types of stromal cells were distinguished: stellate and spindle
      shaped. All stromal cells are alkaline phosphatase-positive. TEM showed that both
      types of stromal cells have cytoplasmic processes of various length and calibre,
      coming into contact with each other as well as with endothelial cells and
      osteoblasts or bone lining cells. Capillaries were found to have a continuous
      endothelial lining; occasionally endothelial cells radiate cytoplasmic processes
      towards stromal cells. Along all the above-mentioned cellular contacts adherens
      and/or gap junctions were often observed. The results of the present study,
      together with our previous findings on osteoblast-osteocyte relationships, show
      that the cells of the osteogenic lineage form a continuous protoplasmic network
      that extends from the osteocytes to the vascular endothelium, passing through
      osteoblasts (or bone lining cells) and stromal cells. The occurrence of gap
      junctions among this cytoplasmic network, namely of junctions enabling metabolic
      and electric coupling, indicates that it forms a functional syncytium, suggesting
      the hypothesis that the activity of the cells pertaining to the osteogenic
      lineage might be regulated not only by diffusion (volume transmission) through
      the intercellular fluids of systemic (hormones) and local factors (cytokines,
      etc.) but also by signals issued through the cytoplasmic network of the
      osteogenic cells (wiring transmission).

PMID- 9623669
TI  - Intravenous injection of guanylin induces mucus secretion from goblet cells in
      rat duodenal crypts.
AB  - Guanylin, structurally related to the heat-stable enterotoxin of E. coli, is a 15
      amino-acid peptide isolated from rat small intestine. We investigated the
      morphological effects of an intravenous injection of rat and human guanylin upon
      the rat intestine. Various doses of rat guanylin were injected intravenously in
      anesthetized rats. After 5, 10 and 30 min, rats were killed by intracardiac
      perfusion with aldehyde fixative, and specimens of the intestine were then
      prepared for light and electron microscopy. Intravenously injected rat guanylin
      rapidly induced mucus secretion from crypt goblet cells in the duodenum. About
      half of the crypt goblet cells secreted mucous granules by compound exocytosis
      within 5 min. The villus goblet cells, in contrast, were not sensitive to
      guanylin. Goblet cells in the jejunum were less responsive than those in the
      duodenum. This secretory response was rare in the ileum and colon. Human guanylin
      produced similar results. The mucus secretion induced by guanylin was inhibited
      by a prior-injection of atropine, but not hexamethonium. Moreover, guanylin
      induced intense edema in the mucosa and submucosa of the small intestine 5 min
      after the injection, which disappeared after 30 min. A prior-injection of
      atropine did not block the appearance of edema. In conclusion, the intravenous
      injection of guanylin induces two phenomena related to water movement: (1)
      compound exocytosis of mucous granules from crypt goblet cells in the rat
      duodenum and jejunum; (2) perineural, inter-epithelial and intra-epithelial edema
      in the rat small intestine.

PMID- 9623670
TI  - Astroglial interlaminar processes in the cerebral cortex of prosimians and Old
      World monkeys.
AB  - Previous observations have shown that astrocytes with interlaminar processes are
      present in the cerebral cortex of humans and New and Old World monkeys, but not
      in the rodent. The present report furthers the analysis of possible evolutionary
      aspects regarding the expression of such astroglial features. A comparison
      between young and adult Microcebus murinus, a prosimian, and Old World monkeys
      (Macaca mulatta and Papio hamadryas) is presented. Brain samples were processed
      for glial fibrillary acidic protein (GFAP), vimentin, MAP2 and SMI 311
      immunocytochemistry, using different procedures. The cerebral cortex of adult
      Microcebus showed the presence of long astroglial processes, albeit reduced in
      number and length with respect to those observed in Old World monkeys. Macaca and
      Papio showed dense packing of such processes extending in most cortical regions
      to a depth of approximately 700 micrometers. Based on double immunolabelling for
      GFAP and MAP 2 antigens, the location and extent of these processes was shown to
      overlap with areas traversed by bundles and individual apical dendrites. Aged Old
      World specimens depicted an increased thickness of terminal portions of
      interlaminar processes, with increased morphological alterations. Comparisons
      made between the average thickness of the "brush" composed of interlaminar
      processes and the thickness of lamina I among the species analyzed disclosed an
      absence of relationship between them. This suggests that interlaminar processes
      do not represent cellular adaptations to the increase in thickness in superficial
      cortical laminae, but rather to some other evolutionary pressure. Since
      astroglial interlaminar processes are already present in a prosimian, although in
      a comparatively reduced manner, it is suggested that such processes underwent an
      early expression within the primate order, with increasing presence in more
      recent primate species.

PMID- 9623671
TI  - Facial nerve parasympathetic preganglionic afferents to the accessory otic
      ganglia by way of the chorda tympani nerve in the cat.
AB  - The distribution of accessory otic ganglia and connections between the ganglia
      and the chorda tympani nerve were investigated in the cat in order to determine
      the parasympathetic preganglionic facial nerve afferents to the otic ganglia
      using whole mount acetylthiocholinesterase (WATChE) histochemistry. The otic
      ganglia consist of a single main prominent ganglion and many small accessory
      ganglia lying on a plexus around the origins of the branches of the mandibular
      nerve and near the junction of the chorda tympani nerve and lingual nerve. In
      cell analysis of Nissl-stained preparations, the neurons composing the accessory
      otic ganglia were morphologically similar to the main otic ganglion neurons.
      Connecting branches from the chorda tympani nerve to the peripherally located
      accessory otic ganglia were found and they were not stained by WATChE
      histochemistry. WATChE-positive connecting branches from the ganglia to the
      inferior alveolar, lingual, and mylohyoid nerves were also found in the same
      preparations. The WATChE histochemistry on various autonomic nervous tissues
      revealed that autonomic postganglionic nerve fibers are selectively stained
      darkly and that preganglionic fibers remain unstained. Therefore, it is
      considered that the WATChE-negative connections from the chorda tympani nerve
      consist chiefly of autonomic preganglionic fibers, whereas the WATChE-positive
      connections to the branches of the mandibular nerve are mainly postganglionic
      fibers. This suggests that some of the facial nerve parasympathetic preganglionic
      fibers in the chorda tympani nerve are mediated in the accessory otic ganglia and
      then join the branches of the mandibular nerve to supply the target mandibular
      tissues.

PMID- 9623672
TI  - Quantitative relationships of normal cartilage volumes of the human knee joint-
      assessment by magnetic resonance imaging.
AB  - The objective of this study was to assess the normal range of cartilage volumes
      in the knee joints of healthy adults, the ratio between the patellar, femoral,
      and tibial cartilages, and the correlation of the volumes with age, body weight,
      height, body mass index (obesity), patellar bone size, and the diameter of the
      tibial head. We examined the knee joints of nine healthy volunteers and eleven
      normal post-mortem specimens with an age range of 24 to 82 years. The cartilage
      volumes of the patella, femur, medial tibia and the lateral tibia were
      quantified, using a fat-suppressed FLASH-3D sequence (resolution 2x0.31x0.31 mm3)
      and digital postprocessing, involving three-dimensional reconstruction. The mean
      total volume of the knee joint cartilage was 23,245 mm3, the relative standard
      deviation (CV%) 19%, and the range 16,341 to 33,988 mm3. In the patella, femur
      and tibia, the CV% amounted to between 22 and 25%. These joint surfaces occupied
      a relatively variable proportion of the total knee joint volume, the percentage
      of the patella being 11 to 22%, that of the femur 54 to 69%, that of the medial
      tibia 7 to 12%, and that of lateral tibia 11 to 16%. The volumes of the lateral
      tibia were systematically higher than those of the medial tibia (P<0.001). There
      was no significant correlation of the knee joint cartilage volume with age
      (r=+0.05), body weight (r=+0.38), height (r=+0.39) or body mass index (r=+0.29),
      but a relatively high correlation with the diameter of the tibial head (r=+0.78,
      P<0.001). After normalising the volumes to this diameter, the CV% of the total
      knee joint cartilage volume was reduced to 13%, its variation being 12 to 21% in
      the patella, femur and tibia. MRI is available for measuring cartilage volume
      during growth, functional adaptation, and tissue loss in degenerative joint
      disease. The study shows that a wide variation of cartilage volumes exists in the
      knee joints of normal adults. To reduce the variability between individuals, the
      cartilage volumes may be normalised to the head of the tibial diameter.

PMID- 9623673
TI  - Disturbed vagal nerve distribution in embryonic chick hearts after treatment with
      all-trans retinoic acid.
AB  - The distribution of the vagal nerve was studied in whole-mount specimens and
      serial sections of chick embryos after retinoic acid treatment. White Leghorn
      chick embryos were treated at stage 15 either with 1 microg all-trans retinoic
      acid (n=11), or with the solvent dimethylsulphoxide (sham-operated embryos, n=8).
      Eight embryos served as normal controls. At stage 34 all 27 embryos were examined
      with a dissecting microscope. In order to reveal the vagal patterning, the hearts
      were removed and whole-mount stained with the HNK-1 antibody. In three hearts of
      the retinoic acid-treated group a morphologic intracardiac anomaly -- a double
      outlet right ventricle -- was found. To explore in depth the vagal nerve
      distribution in the heart, a separate set of hearts of retinoic acid embryos
      (n=5), sham-operated (n=4) and control embryos (n=5), was devised solely for
      serial sectioning and staining with the HNK-1 antibody. All hearts of retinoic
      acid-treated embryos showed a disturbed vagal nerve distribution both over the
      surface of the heart and within the heart wall. The vagal patterning was not
      altered in the sham-operated embryos compared to controls. It is concluded that
      retinoic acid disturbs the development of vagal nerve patterning regardless of
      the concurrent presence of intracardiac malformations. The mechanism and
      functional implications remain to be investigated.

PMID- 9623674
TI  - Type X collagen is not localized in hypertrophic or calcified cartilage in the
      developing rat trachea.
AB  - Our previous studies have shown that rat tracheal chondrocytes become larger and
      hypertrophic, and that the cartilage matrix calcifies during development. Type X
      collagen is a short collagen molecule identified in hypertrophic and calcified
      cartilage in the growth plate of long bones during endochondral ossification. The
      present study was designed to investigate the distribution of type X collagen in
      rat tracheal cartilage during development before and after hypertrophization and
      calcification. Tracheas from postnatal Wistar rats, newborn, and at 4, 8 and 10
      weeks were fixed along with hind limbs from newborn rats. Serial sections were
      made and adjacent sections were processed for von Kossa staining or
      immunohistochemistry for type X collagen. In addition, the immunoreactivity to
      type II collagen was examined as a control. The anti-type X collagen antibody
      stained hypertrophic and/or calcified cartilage in the newborn rat tibia. The
      immunoreaction for type X collagen was localized in the uncalcified peripheral
      region of tracheal cartilage in 4, 8 and 10-week-old rats. In contrast, the anti
      type X collagen antibody did not show immunoreactivity to hypertrophic or
      calcified cartilage in the central region of the 10-week-old rat tracheal
      cartilage. The present study has suggested that type X collagen is not involved
      in hypertrophization of chondrocytes or calcification of the matrix in developing
      rat tracheal cartilage.

PMID- 9623675
TI  - Distribution of mRNA for the facilitated urea transporter UT3 in the rat nervous
      system.
AB  - Recently, the cDNA encoding the rat urea transporter UT3 has been cloned from rat
      kidney. Here we describe the cellular localization of this transporter in the
      brain as detected by non-radioactive in situ hybridization. UT3 is expressed in
      astrocytes throughout the central nervous system as well as in Bergmann glia in
      the cerebellum. The expression in astrocytes was verified by double staining
      using the astrocytic marker GFAP. UT3 mRNA is also strongly expressed by the
      ependymal cells lining the cerebral ventricles and by Muller cells in the retina.
      Furthermore, UT3 expression was detected in subgroups of neurons in the inferior
      colliculus and dorsal root ganglia, as well as in cells in the anterior pituitary
      gland. Other types of brain cells, including oligodendrocytes, microglia,
      tanycytes, endothelial cells of blood vessels, and epithelial cells in the
      choroid plexus were devoid of UT3 mRNA. Northern blot analysis confirmed that the
      mRNA species in the brain and in dorsal root ganglia are identical, and that
      cultured astrocytes and C6 cells also express the UT3 mRNA. UT3 mRNA expression
      by astrocytes is markedly upregulated in quinolinic acid-induced gliosis,
      possibly as a result of increased urea levels during gliosis induced polyamine
      formation. We propose that UT3 in astrocytes represents a mechanism to control
      urea formed in the brain by equilibrating it throughout the astrocyte network and
      guiding it to blood vessels and the CSF for disposal.

PMID- 9623676
TI  - Expression of a 45K subunit of platelet-activating factor acetylhydrolase in the
      developing mouse cerebellum.
AB  - The 45K subunit of platelet-activating factor acetylhydrolase (PAFAH-45K) is the
      product of a candidate gene for Miller-Dieker lissencephaly. We studied the
      expression of this protein in the developing mouse cerebellar cortex by
      immunochemical and immunohistochemical methods. Western blotting studies
      indicated that PAFAH-45K is more abundant in the fetal than the postnatal period.
      Immunohistochemical studies revealed developmental changes in the localization of
      PAFAH-45K-immunoreactivity, which shifted from the somata of Purkinje cells to
      the neuropil of the molecular layer. Our findings indicate that PAFAH expression
      is developmentally regulated and suggest its role in histogenetic processes in
      the cerebellar cortex other than neuronal migration.

PMID- 9623677
TI  - Utility of molecular epidemiology of tuberculosis.

PMID- 9623678
TI  - Repeated low dose allergen exposure: a new investigational model of asthma as a
      persistent disease?

PMID- 9623679
TI  - Pneumoproteinaemia: a new perspective in the assessment of lung disorders.
AB  - Here we make the hypothesis that the determination of the concentration of lung
      specific secretory proteins in serum or pneumoproteinaemia could be used in the
      evaluation of lung disorders with a similar utility as proteinuria in kidney
      diseases involving the glomeruli. Human and experimental data indicate that
      comparable structural and functional features govern the passage of proteins
      across the lung epithelium/blood barrier and the glomerular filter. The
      concentrations in serum of some lung-specific secretory proteins, such as the
      bronchiolar Clara cell 16 kDa protein (CC16) and alveolar surfactant-associated
      proteins A and B (SP-A and SP-B, respectively), might be used to assess the
      integrity of the bronchoalveolar/blood barrier known to be disrupted in many lung
      disorders. In addition, if this barrier is intact or slightly compromised, these
      proteins might serve as peripheral markers to detect changes in secretory
      epithelial cells in the lung.

PMID- 9623680
TI  - Transmission of tuberculosis in the metropolitan area of Zurich: a 3 year survey
      based on DNA fingerprinting.
AB  - Between 1991 and 1993, 444 inhabitants of the metropolitan area of Zurich were
      reported as confirmed or suspected cases of tuberculosis (TB). Overall, isolates
      of Mycobacterium tuberculosis of 361 patients (90% of the bacteriologically
      confirmed cases) were available to study the frequency of transmission of the
      strains on a molecular level. Restriction fragment length polymorphism (RFLP)
      analysis was performed by using IS6110 and the polymorphic GC-rich sequence
      (PGRS) as genetic markers. Ninety nine isolates shared by 77 patients (21.3%)
      were associated with 28 IS6110-defined clusters. However, secondary typing of low
      copy number isolates decreased the number of clusters to 25, encompassing 81
      isolates from 63 (17.5%) patients. By deoxyribonucleic acid (DNA) fingerprinting
      plus conventional contact tracing, definite transmission of TB was proven in only
      five patients (1.4%) and assumed in 20 patients (5.6%). In all other cluster
      associated isolates, no epidemiological connections between the patients could be
      found using the clinical and sociodemographic data available. The present study
      demonstrates that in the time period studied only minor transmission occurred.

PMID- 9623681
TI  - Increased exhaled nitric oxide in active pulmonary tuberculosis due to inducible
      NO synthase upregulation in alveolar macrophages.
AB  - Nitric oxide (NO) plays an important role in resistance to Mycobacterium
      tuberculosis infection. Our aim was to determine whether inducible NO synthase
      (iNOS) expression and generation of reactive nitrogen intermediates (RNI) by
      alveolar macrophages (AM) are increased in patients infected with M.
      tuberculosis. NO levels in the exhaled air of 19 active pulmonary tuberculosis
      (TB) and 14 control subjects were measured using a chemiluminescence NO analyser.
      The expression of iNOS on AM was studied by labelling AM with anti-mac iNOS
      polyclonal antibody analysed with a flow cytometer. The spontaneous generation of
      RNI by cultured AM was also measured. Data are presented as mean+/-SEM. The level
      of NO in exhaled air was higher in patients with active TB (16.2+/-1.2 parts per
      billion (ppb)) compared to control subjects (6.5+/-0.9 ppb), p<0.0001. Exhaled NO
      decreased with anti-TB treatment. Compared to control subjects (29.0+/-4.5
      fluorescence intensity (FI)), iNOS expression on AM was upregulated in TB
      patients (86.3+/-12.5 FI) p<0.001 and the capacity for spontaneous generation of
      nitrite was enhanced. Nitrite production was inhibited by N(G)-monomethyl-L
      arginine (L-NMMA), a competitive inhibitor of iNOS. The expression of iNOS on AM
      was related to the concentration of exhaled NO (r=0.66, p<0.001) and the nitrite
      generation capacity of AM (r(s)=0.77, p<0.001). We conclude that the increase in
      exhaled nitric oxide observed in patients with active pulmonary tuberculosis is
      due to an upregulation of inhaled NO synthase expression in alveolar macrophages
      which have an enhanced capacity for nitric oxide production.

PMID- 9623682
TI  - Mortality among tuberculosis patients in The Netherlands in the period 1993-1995.
AB  - This study aimed to estimate excess mortality among tuberculosis patients in The
      Netherlands and identify risk factors for tuberculosis-associated mortality. The
      national tuberculosis register provided data on patients diagnosed in the period
      1993-1995. Excess mortality in tuberculosis cases, according to age and sex, was
      determined by comparison with national mortality rates. Risk factors were
      identified and adjustment for confounders was carried out using Cox's
      proportional hazard analysis. Of 4,340 patients alive at diagnosis, 258 died
      within 1 yr while on treatment. The Kaplan-Meier survival probability after 1 yr
      was 93%. Tuberculosis patients had a standardized mortality ratio of 8.3.
      Independent risk factors for mortality were: gender; age; presence of a
      malignancy or human immunodeficiency virus (HIV) infection; addiction to alcohol
      or drugs; localization of tuberculosis; and the type of medical officer having
      made the diagnosis. Of all deaths, 83% occurred in two risk groups comprising 21%
      of tuberculosis patients: those aged > or =65 yrs and those having HIV infection
      or a malignancy. Tuberculosis patients in The Netherlands are at a considerably
      increased risk of death. However, the prognosis is very good for those aged less
      than 65 yrs and without human immunodeficiency virus infection or a malignancy.

PMID- 9623683
TI  - Increases in airway eosinophils and interleukin-5 with minimal
      bronchoconstriction during repeated low-dose allergen challenge in atopic
      asthmatics.
AB  - Repeated low-dose allergen challenge increases airway hyperresponsiveness in
      atopic asthmatics. However, it is not known whether low-dose allergen challenge
      increases airway inflammation. Eight atopic asthmatics were enrolled in a
      controlled, cross-over study to evaluate the effect and time course of repeated
      low-dose allergen challenge on airway inflammation and hyperresponsiveness. The
      dose of allergen to reduce forced expiratory volume in one second (FEV1) by
      approximately 5% was selected in a screening allergen challenge. The subjects
      then were challenged for five consecutive days with either diluent or the
      selected low-dose of allergen. Methacholine airway hyperresponsiveness
      (PC20,meth) was measured and sputum induced on days 1, 3 and 5 of the repeated
      challenge, and then 1 day and 3 days after the last challenge. Repeated low-dose
      allergen challenge caused small reductions in FEV1, but increased airway
      eosinophils and interleukin (IL)-5, airway hyperresponsiveness, asthma symptoms
      and beta2-agonist use, all of which peaked on days 3 or 5 of the challenge. The
      mean (SEM) percentage sputum eosinophils was 21.2 (0.7)% after allergen versus
      3.9 (0.1)% after diluent (p<0.001); percentage EG2+ cells were 13.4 (03)% after
      allergen versus 1.1 (0.04)% after diluent (p<0.01) and geometric mean (GSEM)
      eosinophil cationic protein (ECP) was 1061.8 (1.6) microg x L(-1) after allergen
      versus 447.03 (1.2) microg x L(-1) after diluent (p<0.05). Geometric mean (GSEM)
      IL-5 was 71.4 (1.4) pg x mL(-1) after allergen versus 18.4 (1.04) pg x mL(-1)
      after diluent (p<0.01). All the changes had resolved by 3 days after the last
      challenges. The study demonstrated that repeated inhalation of a low-dose of
      allergen causes airway eosinophilia and increases in interleukin-5, associated
      with airway hyperresponsiveness, and mild worsening of asthma control, without
      the development of marked acute bronchoconstriction or the development of late
      responses.

PMID- 9623684
TI  - Induced sputum, bronchoalveolar lavage and blood from mild asthmatics:
      inflammatory cells, lymphocyte subsets and soluble markers compared.
AB  - Airway inflammation in asthma can be measured directly by invasive
      bronchoalveolar lavage (BAL), directly and relatively noninvasively by induced
      sputum and indirectly from peripheral blood. We compared cellular and fluid phase
      indices of inflammation in induced sputum, BAL and blood from 11 adults with mild
      stable asthma. On one day, induced sputum selected from saliva was collected and
      on the next, blood and BAL. Median results of sputum compared with BAL showed a
      higher number of nonsquamous cells (53 versus 0.8 x 10(6) cells x mL(-1),
      p=0.003), more neutrophils (34.3 versus 1.0%, p<0.001), CD4+ and CD19+ T-cells
      (76.5 versus 54.7%, p=0.01 and 5.2 versus 1.1%, p=0.03, respectively), fewer
      macrophages (603 versus 95.0%, p=0.002) and markedly higher levels of eosinophil
      cationic protein (ECP) (264 versus 2.0 microg x L(-1), p<0.001), tryptase (17.6
      versus 2.2 UI x L(-1), p<0.001) and fibrinogen (1,400 versus 150 microg x L(-1),
      p=0.001). Sputum and BAL neutrophils and CD4+ T-cells were strongly correlated.
      Sputum and BAL differed from blood by having higher proportions of T-cells (94.9
      and 98.9% versus 87.7%, p=0.002) and lower proportions of CD19+ T-lymphocytes
      (p=0.04 and 0.006). Sputum also differed from blood by having higher proportions
      of CD4+ T-cells (76.5 versus 51.4%, p=0.001), lower proportions of CD8+ cells
      (24.0 versus 403%, p=0.04) and a higher CD4+/CD8+ ratio (3.3 versus 1.4, p=0.01).
      We conclude that in mild asthmatics, sputum, bronchoalveolar lavage and blood
      measure different compartments of inflammation. Induced selected sputum has the
      advantage over bronchoalveolar lavage of higher density of cell recovery and
      stronger signal for fluid-phase markers.

PMID- 9623685
TI  - Effect of a platelet-activating factor (PAF) antagonist, SR 27417A, on PAF
      induced gas exchange abnormalities in mild asthma.
AB  - Inhaled platelet-activating factor (PAF), both in normals and in asthmatic
      patients, provokes transient systemic effects, neutropenia, bronchoconstriction
      and arterial oxygenation abnormalities similar to those shown in spontaneous
      exacerbations of asthma. To investigate the efficacy of a new PAF-receptor
      antagonist, SR 27417A, on all these changes after PAF challenge, 12 nonsmoking
      patients (four females and eight males) (mean+/-SEM) age 24+/-1 yrs with mild
      asthma (forced expiratory volume in one second (FEV1) 93+/-3% predicted) were
      studied in a double-blind, placebo-controlled, cross-over fashion 2 weeks apart.
      PAF aerosol challenge (18 microg) was carried out 3 h after oral administration
      of either SR 27417A (20 mg) or placebo. Respiratory system resistance (Rrs) and
      arterial blood gases and neutrophil cell counts were measured at baseline, before
      compound/placebo administration, and at 5, 15 and 45 min after PAF. Compared to
      vehicle, SR 27417A brought about moderate attenuation of PAF-induced neutropenia
      at 5 min (by 140%; p<0.025), and rebound neutrophilia at 15 and 45 min (p<0.025),
      increases of Rrs (by 90-65%) (p<0.01) and of alveolar-arterial pressure
      difference for oxygen (PA-a,O2) at 5 min (by 68%) and 15 min (by 63%), and
      decreases of arterial oxygen tension (Pa,O2) at 5 min (by 57%; p<0.025, each).
      Furthermore, systemic effects and platelet aggregation tests (p<0.001) were
      abolished after the administration of the compound. We conclude that SR 27417A is
      effective in inhibiting systemic, cellular and pulmonary effects after platelet
      activating factor challenge in patients with mild bronchial asthma.

PMID- 9623686
TI  - Asthma and allergies among children in West and East Germany: a comparison
      between Munster and Greifswald using the ISAAC phase I protocol. International
      Study of Asthma and Allergies in Childhood.
AB  - The study aim was to compare the prevalence of asthma, rhinitis and eczema in
      children living in Munster, western Germany, and Greifswald, eastern Germany, and
      to investigate associations of several characteristics and exposures with atopic
      disease symptoms. In 1994 and 1995, questionnaire information was gathered on 5-8
      yr old children (n=3,741 in Munster and n=2,857 in Greifswald) and 12-15 yr olds
      (n=4,003 and n= 3,153, respectively) using the phase I protocol of the
      International Study of Asthma and Allergies in Childhood (ISAAC). The 12 month
      period prevalences of reported atopic disease symptoms in 5-8 yr olds were
      generally higher in Munster than in Greifswald, whereas only a few prevalence
      differences were observed in 12-15 yr olds. In both age groups the reported
      lifetime prevalences of asthma, hay fever and eczema were lower in Greifswald.
      Indoor exposures such as wood or coal heating and feather bedding were negatively
      associated with symptoms, whereas exposures such as truck traffic in a
      residential street or active smoking were positively associated with symptoms.
      Wood or coal heating could partly explain the prevalence difference of allergic
      rhinitis symptoms among 5-8 yr olds between Munster and Greifswald. The findings
      provide additional evidence for a role of several characteristics and exposures
      as potential determinants of asthma and allergies in children.

PMID- 9623687
TI  - Persistence of sputum eosinophilia in children with controlled asthma when
      compared with healthy children.
AB  - We aimed to describe induced sputum cell counts in healthy nonasthmatic children,
      and to compare these to children with controlled and uncontrolled asthma.
      Following clinical assessment and spirometry, ultrasonically nebulized hypertonic
      saline was used to induce sputum from children with asthma (n=50) and without
      asthma (n=72). Sputum was dispersed and cell counts performed to yield total and
      differential cell counts. Specific stains were used for eosinophil and mast cell
      counts. All of the children with asthma were receiving inhaled and/or oral
      corticosteroids. Current asthma control was assessed in terms of symptoms and
      lung function. Children were classified as controlled on inhaled corticosteroids
      (no current symptoms, normal lung function n=15), current symptomatic asthma
      (n=16) and asthma exacerbation (n=11). It was found that eosinophils comprised a
      median 0.3% (interquartile range (IQR): 0, 1.05) of cells in sputum from healthy
      children. Sputum eosinophils (4.3% (IQR: 15, 14.1) p=0.0005) and epithelial cells
      (14% (IQR: 6, 19.4) p=0.0005) were significantly higher in children with asthma
      than in nonasthmatic children. Children whose asthma was controlled, as well as
      those with symptoms, had more sputum eosinophils and epithelial cells than the
      nonasthmatics. Mast cells were found in the sputum of only four of the 42
      children with asthma. This study demonstrates that eosinophilic airway
      inflammation and epithelial damage can occur in children with asthma. Airway
      inflammation persists even in those children who are receiving inhaled
      corticosteroids, have normal lung function and good symptomatic control of their
      disease.

PMID- 9623688
TI  - Haemodynamics in children during rest and exercise: methods and normal values.
AB  - Measuring haemodynamic performance in children is either invasive, and thus
      unacceptable, or noninvasive when the measured variable is often remote from the
      true variable. Measuring only maximum performance variables relies too heavily on
      motivation, especially in disease groups. We describe a method for the
      measurement of haemodynamic performance using respiratory mass spectrometry
      during rest, exercise and recovery therefrom. One hundred and six healthy
      children (55 male, 51 female) aged 8-16.9 yrs underwent an identical exercise
      protocol. Following studies at rest, they initially bicycled at 25 W x m(-2),
      increasing every 3 min by 15 W x m(-2) until exhaustion, after which measurements
      were made during recovery. Effective pulmonary blood flow, stroke volume, oxygen
      consumption, arteriovenous oxygen difference and functional residual capacity
      (FRC) together with estimates of pulmonary capillary blood volume and transit
      time were assessed at every exercise stage using inert gas rebreathing
      techniques. Haemodynamic performance is highly dependent on surface area, age,
      gender and pubertal stage. Many parameters, for example transfer factor,
      demonstrate pubertal stage-dependent differences at identical workloads even
      after correction for size. Females have a lower capillary blood volume at rest
      compared to age and size-matched males, but it is equalized during exercise. FRC
      unexpectedly rose with exercise, and peak exercise was associated with a falling
      stroke volume in 91% (95% CI 84-96%) of children, a possible demonstration of
      Starling's law of the heart. Oxygen pulse (oxygen consumption/cardiac frequency)
      is a very poor marker for pulmonary blood flow. Normal values are provided for
      all haemodynamic parameters for rest and every exercise stage for all subgroups
      of children. This should allow accurate comparison of normal and disease groups
      in future.

PMID- 9623689
TI  - Breathing patterns in children with craniofacial dysostosis and hindbrain
      herniation.
AB  - In the past few years, hindbrain herniation has become recognized as a frequent
      feature of the child with syndromic craniofacial dysostosis. The clinical
      significance of hindbrain herniation in these disorders is unclear. Abnormalities
      of respiratory control have frequently been reported. The aim of the present
      study was to document the incidence of obstructive and central respiratory
      abnormalities during sleep in craniofacial syndromes with hindbrain herniation.
      We performed cardiorespiratory sleep studies during unsedated night-time sleep in
      a group of 13 children. Hindbrain herniation was confirmed by magnetic resonance
      imaging (MRI) and ranged 1.5-26.9 mm below the cranial base. Sleep studies
      revealed central respiratory pauses associated with important reduction of the
      arterial oxygen saturation (Sa,O2) in only two of 13 cases (minimum Sa,O2 86% and
      87%). In contrast 10 of 13 children had some degree of upper airway obstruction
      (four mild, three moderate and three severe). Of the remaining three children,
      two had previous long-term tracheostomies. Changes in the breathing pattern were
      proportional to the severity of the obstruction and comprised increased
      respiratory efforts and arterial oxygen desaturation. Infrequent mixed apnoeas
      were observed in five patients, and their severity reflected the severity of the
      obstructive component. In conclusion, obstruction of the upper airways was the
      predominant sleep-related respiratory problem in this group of patients.
      Hindbrain herniation was not associated with a high incidence of central sleep
      apnoea.

PMID- 9623690
TI  - Alpha1-antitrypsin deficiency alleles and the Taq-I G-->A allele in cystic
      fibrosis lung disease.
AB  - Cystic fibrosis (CF) is characterized by progressive and ultimately fatal
      pulmonary disease although there are notable variations in clinical features.
      This heterogeneity is thought to lie outside the cystic fibrosis transmembrane
      regulator (CFTR) gene locus and may stem from deficiencies in the antiproteinase
      screen that protects the lung from proteolytic attack. One hundred and fifty
      seven patients were recruited from two UK CF centres. The serum concentrations of
      alpha1-antitrypsin, alpha1-antichymotrypsin and C-reactive protein (CRP) were
      determined and patients were screened for the common S and Z deficiency alleles
      of alpha1-antitrypsin and the G-->A mutation in the 3' noncoding region of the
      alpha1-antitrypsin gene (Taq-I G-->A allele). Alpha1-antitrypsin deficiency
      phenotypes were detected in 20 (16 MS, 1 S and 3 MZ) out of 147 unrelated tested
      CF patients and were, surprisingly, associated with significantly better lung
      function (adjusted mean forced expiratory volume in one second (FEV1) 62.5% of
      predicted for deficient group and 51.1% pred for normal alleles; p=0.043). The
      Taq-I G-->A allele was found in 21 out of 150 unrelated patients and had no
      significant effect on CF lung disease or on levels of alpha1-antitrypsin during
      the inflammatory response. We show here that, contrary to current thinking,
      common mutations of alpha1-antitrypsin that are associated with mild to moderate
      deficiency of the protein predict a subgroup of cystic fibrosis patients with
      less severe pulmonary disease. Moreover, the Taq-I G-->A allele has no effect on
      serum levels of alpha1-antitrypsin in the inflammatory response, which suggests
      that the previously reported association of the Taq-I G-->A allele with chronic
      obstructive pulmonary disease is not mediated by its effect on the serum level of
      alpha1-antitrypsin.

PMID- 9623691
TI  - Nasal prongs in the detection of sleep-related disordered breathing in the sleep
      apnoea/hypopnoea syndrome.
AB  - Conventional systems to monitor oronasal flow in sleep studies have traditionally
      relied on a thermistor signal. Our study was designed to verify whether nasal
      prongs (NP) connected to a pressure transducer could improve respiratory events
      detection in patients with sleep apnoea/hypopnoea syndrome (SAHS) compared to
      traditional systems. Sleep episodes from a 2 h conventional polysomnographic
      record plus NP signal obtained at random from eight patients (age: mean(+/-SD)
      53(+/-12) yrs; body mass index (BMI): 29(+/-6) kg x m(-2); apnoea/hypopnoea index
      (AHI): 27(+/-20) events x h(-1)) were identified and used for analysis. An
      abnormal change in the pattern of any of the respiratory or neurological
      variables occurring during the observation period was defined as an episode. Each
      episode was registered and scored with concomitant scoring of the remaining
      variables. According to the episode definition three different profiles were
      established: 1) periods of reduction of ventilation in either variable without an
      arousal or cyclical desaturation, named nonpathological episode (NPE); 2) an
      idiopathic or nonrespiratory arousal (IA); and 3) a true respiratory event (TRE)
      defined as reduction or absence of flow demonstrated by either thermistor,
      thoraco-abdominal bands or NP accompanied by cyclical desaturation and/or
      arousal. For each TRE, its detection by thermistor, thoraco-abdominal bands or NP
      was established. A total of 877 sleep episodes were observed (42 NPE, 30 IA and
      805 TRE). When compared to single or combined thermistor and bands approach, NP
      had the highest respiratory events detection rate, 779 (96.8%) versus 673 events
      (83.6%), respectively. Detection of respiratory-related arousals was also
      improved by NP and only 3% could account for mouth breathing respiration. It is
      concluded that nasal prongs improve the detection of respiratory events in
      patients with sleep respiratory disorders.

PMID- 9623692
TI  - Snoring and hypertension: a 10 year follow-up.
AB  - In many cross-sectional studies an association has been found between snoring and
      hypertension. However, differing results have been obtained when confounding
      factors have been taken into account. To establish whether snoring is a risk
      factor for developing hypertension, a population-based, prospective survey was
      performed. In 1984 and 1994, 2,668 males, aged 30-69 yrs at baseline, answered
      questionnaires concerning sleep disturbances and somatic disease. Of the habitual
      snorers in 1984, 12.5% reported that they had developed hypertension during the
      period, compared with 7.4% of the remaining subjects (p<0.001). In a multiple
      logistic regression model persistent snoring, i.e., reported habitual snoring in
      both 1984 and 1994, was found to be an independent predictor for the development
      of hypertension among males aged 30-49 yrs (odds ratio 2.6, 95% confidence
      interval 1.5-4.5) after adjustments for age, body mass index (BMI), weight gain,
      smoking, alcohol dependence, and physical inactivity. Among the subjects aged 50
      69 yrs in 1984, no association between snoring and development of hypertension
      was found. Although based only on reported data, the results indicate that
      persistent snoring is an independent risk factor for the development of
      hypertension among males aged <50 yrs. Prospective surveys, including whole-night
      sleep recordings, are needed to establish whether this is due to a higher
      prevalence of obstructive sleep apnoea syndrome among snorers or whether
      nonapnoeic snorers with increased upper airway resistance also have an increased
      risk of developing hypertension.

PMID- 9623693
TI  - Impact of nasal continuous positive airway pressure treatment on quality of life
      in patients with obstructive sleep apnoea.
AB  - Quality-of-life (QoL) issues have become increasingly important in health care
      practice and research. Obstructive sleep apnoea syndrome (OSAS) results in an
      especially serious reduction in QoL. The purpose of this study was to measure the
      QoL (life satisfaction) of OSAS patients treated with nasal continuous positive
      airway pressure (nCPAP). We aimed to determine whether and to what extent the QoL
      of OSAS patients using nCPAP differs from that of randomly selected subjects
      without this disorder. The QoL of 67 patients treated for at least 3 months with
      nCPAP, 21 OSAS patients at the time of OSAS diagnosis, and 113 randomly selected
      persons visiting the hospital (controls) was investigated with the help of the
      Munich life-quality dimension list (MLDL), an instrument for cognitive assessment
      of elementary components (physical condition, psyche, social life, everyday life)
      of QoL. It was found that QoL of OSAS patients treated with nCPAP did not
      significantly differ from that of control subjects with regard to elementary
      components. The 21 untreated OSAS patients showed significantly lower scores in
      all four subcategories: physical condition (p<0.0005), psyche (p<0.01), social
      life (p<0.0005) and everyday life (p<0.007). Thus, it may be concluded that nasal
      continuous positive airway pressure therapy has an important impact on the
      quality of life of obstructive sleep apnoea syndrome patients, and signifies a
      further advantage in addition to clinical aspects. Treated patients are as
      satisfied or dissatisfied with their life as persons without this illness.

PMID- 9623694
TI  - Effects of pulmonary and intercostal denervation on the response of breathing
      frequency to varying inspiratory flow.
AB  - In mechanically ventilated awake and sleeping humans, it has been shown that
      increasing inspiratory flow rate (V'I) exerted a reflex excitatory effect on
      respiratory output. Mechanoreceptors located in intercostal muscles or within the
      lung have been suggested as possible pathways that may mediate the excitatory
      effect of V'I. To test this, five patients with bilateral lung transplantation
      (LTP) and eight quadriplegics with spinal cord transection at the level of C6-C7
      (QP) were studied. Patients were connected to a volume cycle ventilator in the
      assist volume-control mode and V'I was randomly changed. V'I pattern was square
      and all breaths were patient-triggered. V'I values of 30, 60 and 90 L x min(-1)
      were studied. Each level of V'I was sustained for 15 breaths. Airway pressures,
      end-tidal partial pressure of carbon dioxide (PCO2), airflows and volumes were
      measured breath by breath. Thirty seven trials in LTP and sixty in QP, where V'I
      was randomly changed between 30 and 90 L x min(-1), were analysed. In both groups
      of patients, minute ventilation increased and total breath duration decreased
      significantly as V'I increased. These changes were complete in the first breath
      after V'I transition, without evidence of adaptation of the response. The
      magnitude of the response did not differ between the two groups of patients and
      was comparable to that observed previously in conscious normal subjects. We
      conclude that the excitatory effect of inspiratory flow rate on breathing
      frequency persists in patients who have pulmonary or intercostal denervation.
      These results do not favour receptors located within the lung (below the
      resection lines) or in the intercostal muscles to mediate the response of
      breathing frequency to flow rate.

PMID- 9623695
TI  - Reproducibility of twitch mouth pressure, sniff nasal inspiratory pressure, and
      maximal inspiratory pressure.
AB  - Twitch mouth pressure (Pmo,tw) during magnetic phrenic nerve stimulation and
      sniff nasal inspiratory pressure (SNIP) were recently proposed as alternative
      noninvasive methods for assessing inspiratory muscle strength. This study aimed
      to compare their reproducibility with maximal inspiratory pressure (MIP) in
      normal subjects. Ten healthy subjects were studied at functional residual
      capacity in semirecumbent position. Cervical magnetic phrenic nerve stimulation
      was performed during gentle expiration against an occlusion incorporating a small
      leak. Constancy of stimulation was controlled by recording diaphragmatic
      electromyogram. Within and between-session reproducibility of pressure were
      studied for Pmo,tw, SNIP, and MIP. The subjects were studied during a session of
      10 manoeuvres repeated after 1 day and 1 month. The mean values were 16 cmH2O for
      Pmo,tw, 118 cmH2O for SNIP, and 115 cmH2O for MIP. For the three tests, the
      within subject variation was small in relation to between-subject variation, with
      the intraclass correlation coefficient ranging 0.79-0.90 for Pmo,tw, 0.85-0.92
      for SNIP, and 0.88-0.92 for MIP. At 1 day interval, the coefficient of
      repeatability (2 SD of differences) was 3.6 cmH2O for Pmo,tw, 32 cmH2O for SNIP
      and 28 cmH2O for MIP. At 1 month interval, the coefficient of repeatability was
      5.8 cmH2O for Pmo,tw, 23 cmH2O for SNIP and 21 cmH2O for MIP. We conclude that
      the within session reproducibility of the new tests twitch mouth pressure and
      sniff nasal inspiratory pressure is sufficient to be clinically useful. For sniff
      nasal inspiratory pressure, the between session reproducibility established after
      1 day was maintained after 1 month. For twitch mouth pressure, the between
      session reproducibility declined slightly after 1 month. These characteristics
      should be considered when using these methods to follow an individual patient
      over time.

PMID- 9623696
TI  - Structure and function relationships of the respiratory muscles.
AB  - Potential relationships between the structure of the diaphragm and external
      intercostals and several indices of respiratory muscle function, lung function
      and nutrition in 27 patients (61+/-10 yrs of age) subjected to thoracotomy as a
      result of a lung neoplasm have been investigated. Prior to surgery the
      nutritional status of the patients was assessed and lung function (spirometry,
      lung volumes, transfer factor of the lungs for carbon monoxide, arterial blood
      gases) and respiratory muscle function (maximal inspiratory pressure (MIP) and
      diaphragmatic function were measured). Biopsies of the diaphragm (and external
      intercostals) were obtained during surgery. On average, patients showed mild
      airflow limitation (forced expiratory volume in one second (FEV1), 70+/-14% of
      predicted value, FEV1/forced vital capacity (FVC), 70+/-9%) with some air
      trapping (residual volume (RV), 139+/-50% pred) and normal gas exchange (arterial
      oxygen tension (Pa,O2), 11.3+/-1.33 kPa (85+/-10 mmHg)) and arterial carbon
      dioxide tension (Pa,CO2) 5.4+/-0.5 kPa (40.6+/-4 mmHg). MIP was 77+/-25% pred;
      maximal transdiaphragmatic pressure was 90+/-27 cmH2O. Most morphometric
      measurements of the diaphragm and external intercostals were within the range of
      values reported previously in other skeletal muscles. The size of the fibres of
      these two respiratory muscles was positively related (p<0.05) to MIP (% pred).
      There were no significant relationships between the structure of both muscles and
      nutritional status or any index of lung function. In conclusion, in the
      population studied, the fibre size of the diaphragm and external intercostals
      appears to relate to their ability to generate force.

PMID- 9623697
TI  - Expression of plasminogen activator inhibitors type-1 and type-2 in the mouse
      lung after administration of crystalline silica.
AB  - Altered expression of plasminogen activator inhibitors (PAIs) is of potential
      relevance to the process of lung fibrosis. To clarify the involvement of PAIs in
      interstitial lung diseases, we examined whether alterations in PAI-1 and PAI-2
      were induced in response to a single intratracheal administration of a fibrosing
      dose of crystalline silica in mice (5 mg x animal(-1)). The time course of
      changes in PAI activity and PAI-1 protein were characterized in bronchoalveolar
      lavage fluid (BALF) and changes in PAI-1 and PAI-2 messenger ribonucleic acid
      (mRNAs) were monitored by reverse transcriptase polymerase chain reaction (RT
      PCR) in BALF cells and lung tissue up to the fibrotic stage of the disease.
      Substantial levels of PAI activity were found in BALF of control animals, whereas
      no PAI-1 protein was detected. In response to silica treatment, we observed an
      acute increase of PAI activity and PAI-1 protein levels in BALF (day 1),
      associated with an induction of PAI-1 and PAI-2 mRNA levels in lung tissue. In
      alveolar macrophages, silica treatment induced a persistent upregulation of PAI-2
      mRNA only. One month after silica treatment, PAI activity was undetectable in
      BALF while substantial PAI activity was still present in controls. At the same
      time point, sustained upregulation of PAI-1 and PAI- 2 mRNAs was, however, noted
      in lung tissue of animals treated with silica. These findings support the
      possible implication of PAIs in the remodelling process induced by silica in the
      lung.

PMID- 9623698
TI  - Time-course of functional and pathological changes after a single high acute
      inhalation of chlorine in rats.
AB  - Reactive airways dysfunction syndrome (RADS) is an asthma-like condition that
      follows exposure to very high concentrations of an irritant material. We assessed
      the time-course of pathophysiological alterations in a model of RADS. Sprague
      Dawley rats were exposed to 1,500 parts per million (ppm) of chlorine for 5 min.
      Lung resistance (RL), responsiveness to inhaled methacholine (MCh), the airway
      epithelium and bronchoalveolar lavage (BAL) were assessed over a 3 month period
      after exposure. RL increased significantly up to 3 days after exposure, reaching
      a maximal change of 110+/-16% from baseline. There was a significant decrease in
      the concentration of MCh required to increase RL by 0.20 cmH2O x mL(-1) x s from
      days 1-7 after exposure. In some rats, MCh hyperresponsiveness and RL changes
      persisted after exposure for as long as 1 and 3 months, respectively.
      Histological evaluation with morphometric evaluation revealed epithelial
      flattening, necrosis, increase in smooth muscle mass and evidence of epithelial
      regeneration. BAL showed an increased number of neutrophils. The timing of
      maximal abnormality in the appearance of the epithelium (days 1-3) corresponded
      to that of the maximal functional changes. Acute high chlorine exposure results
      in functional and pathological abnormalities that resolve in the majority of
      animals after a variable period; however, these changes can persist in some
      animals. Functional abnormalities in the initial stages may be related to airway
      epithelial damage.

PMID- 9623700
TI  - Nebulizer calibration using lithium chloride: an accurate, reproducible and user
      friendly method.
AB  - Conventional gravimetric (weight loss) calibration of jet nebulizers
      overestimates their aerosol output by up to 80% due to unaccounted evaporative
      loss. We examined two methods of measuring true aerosol output from jet
      nebulizers. A new adaptation of a widely available clinical assay for lithium
      (determined by flame photometry, LiCl method) was compared to an existing
      electrochemical method based on fluoride detection (NaF method). The agreement
      between the two methods and the repeatability of each method were examined. Ten
      Mefar jet nebulizers were studied using a Mefar MK3 inhalation dosimeter. There
      was no significant difference between the two methods (p=0.76) with mean aerosol
      output of the 10 nebulizers being 7.40 mg x s(-1) (SD 1.06; range 5.86-9.36 mg x
      s(-1)) for the NaF method and 7.27 mg x s(-1) (SD 0.82; range 5.52-8.26 mg x s(
      1)) for the LiCl method. The LiCl method had a coefficient of repeatability of 13
      mg x s(-1) compared with 3.7 mg x s(-1) for the NaF method. The LiCl method
      accurately measured true aerosol output and was considerably easier to use. It
      was also more repeatable, and hence more precise, than the NaF method. Because
      the LiCl method uses an assay that is routinely available from hospital
      biochemistry laboratories, it is easy to use and, thus, can readily be adopted by
      busy respiratory function departments.

PMID- 9623699
TI  - Work-related changes in peak expiratory flow among laboratory animal workers.
AB  - Laboratory animal workers are at risk of developing allergic symptoms, of which
      asthmatic symptoms are the most severe. The aim was to study the relationship
      between allergic symptoms due to working with rats and variability and changes in
      peak expiratory flow (PEF). Several indices were used on the basis of the
      amplitude of the PEF or the differences in PEF between days with and without
      exposure to rat aeroallergens. Of the 398 rat workers, 73% completed PEF readings
      on at least 9 days, of whom 208 had PEF readings on working days with and without
      contact with animals. The overall prevalence rate of allergic symptoms
      (asthmatic, eye, nose and/or skin) among rat workers during the handling of rats
      was 17.3%. Asthmatic symptoms were reported by 6.7%. The PEF of the workers who
      reported asthmatic symptoms due to working with rats decreased significantly on
      days working with the animals (difference between the minimum PEF averaged over
      working days with animals and over days without animals (deltaPEFmin-min) = -73 L
      x min(-1)), compared to the workers without symptoms (2.2 L x min(-1)). This
      effect was more pronounced among workers with a late asthmatic response, i.e. the
      presence of asthmatic symptoms several hours after working with rats (deltaPEFmin
      min = -11.6 L x min(-1)). Multiple regression analyses showed that only those
      with asthmatic symptoms several hours after working with rats and those with
      allergic symptoms had an increased deltaPEFmin-min. In addition, workers with
      asthmatic symptoms were also more likely to have a higher PEF variability than
      workers without asthmatic symptoms. However, no difference in PEF variability
      between days with and without animals contact was observed. This study shows that
      the peak expiratory flow of workers who reported asthmatic symptoms due to
      working with rats decreased significantly on days working with laboratory
      animals.

PMID- 9623701
TI  - Reproducibility of spirometrically controlled CT lung densitometry in a clinical
      setting.
AB  - The aim of this study was to assess the reproducibility of quantitative,
      spirometrically gated computed tomographic (CT) lung densitometry at defined
      levels of inspiration in hospitalized patients. On two consecutive days,
      spirometrically gated CT sections were obtained from 20 hospitalized patients at
      5 cm above and 5 cm below the carina, and at 90 and 10% of the vital capacity
      (VC). The mean, modal and median lung densities were calculated, the cut-off
      points of the frequency distribution of Hounsfield units (HU) defining the lowest
      and the highest 10th percentile, as well as the histogram full width at half
      maximum. The lung density parameters of corresponding CT sections of both studies
      were compared. Reproducibility was expressed as the standard deviation of the
      signed difference between the results of Day 1 and Day 2 divided by the square
      root of 2. Reproducibility data were correlated with results of airflow
      limitation. At 90% VC, reproducibility was of the order of 3-14 HU in both lung
      zones. At 10% VC, reproducibility was worse by approximately a factor of three.
      No relationship was found between reproducibility and results of airflow
      limitation. In conclusion, objective measurement of lung density at
      spirometrically controlled levels of inspiration is a reproducible method in
      assessing pulmonary density. Reproducibility of lung density measurements is not
      influenced by severe respiratory insufficiency. The most reproducible computed
      tomographic lung density measurements can be obtained at 90% vital capacity.

PMID- 9623702
TI  - Stability of methacholine chloride solutions under different storage conditions
      over a 9 month period.
AB  - Methacholine chloride solutions, routinely used for testing bronchial
      hyperreactivity, have been shown to degrade over time. The data published
      addressing the optimal conditions for methacholine chloride storage are
      conflicting and incomplete. This study investigated the effects of a variety of
      conditions on the stability of methacholine chloride. Methacholine chloride,
      dissolved in phosphate buffered saline (PBS) or sodium chloride (NaCl) at 50 and
      0.39 g x L(-1), was subjected to various light and temperature conditions for 9
      months. Methacholine chloride degradation was determined by high performance
      liquid chromatography, and all solutions underwent bacterial and pH testing. By 9
      months, all 50 g x L(-1) solutions of methacholine chloride had degraded by 65+/
      0.8%. All 0.39 g x L(-1) solutions in NaCl had degraded by 11.0+/-0.33%. The 0.39
      g x L(-1) solutions in PBS which had been frozen, refrigerated or stored at room
      temperature had degraded by 8.0%, 16.0+/-0.3% and 63.8+/-0.5%, respectively. The
      pH of methacholine chloride was 7.2 in PBS at 0.39 g x L(-1), 5.8 in PBS at 50 g
      x L(-1), 3.9 in NaCl at 0.39 and 2.7 in NaCl at 50 g x L(-1). Bacterial
      contamination was minimal. The results of this study demonstrate that
      methacholine chloride is more stable at the higher concentration. However, the pH
      of the more concentrated solutions of methacholine chloride in sodium chloride
      could cause bronchoconstriction in some subjects. We therefore recommend storing
      methacholine chloride at 50 g x L(-1) in phosphate-buffered saline.

PMID- 9623703
TI  - The role of ICAM-1 on T-cells in the pathogenesis of asthma.
AB  - The capacity of inflammatory cells to adhere is critical to inflammatory
      responses and involves an array of adhesion molecules grouped into distinct
      families. Intercellular adhesion molecule (ICAM)-1 has recently attracted much
      interest in view of increasing evidence that it plays a prominent role in
      allergic diseases such as asthma and rhinitis. Apart from its role in adhesion of
      inflammatory cells to vascular endothelium, the extracellular matrix and
      epithelium, ICAM-1 mediates T-cell/T-cell, T-cell/target cell and T-cell/B-cell
      interactions. ICAM-1 on the surface of T-cells is thought to participate in
      signal transduction and may thus modulate several functions including activation,
      proliferation, cytotoxicity and cytokine production. Because ICAM-1 is the
      receptor for the major group of rhinoviruses, the most important cause of acute
      asthma attacks, binding of rhinovirus (RV) to ICAM-1 on T-cells may, at least
      theoretically, modulate their function. We review here the role of ICAM-1 in
      asthma and focus more specifically on its expression on T-cells. We present
      evidence for a general increase in ICAM-1 expression in this disease including
      recent observations of enhanced expression on the surface of T-cells in the
      airways lumen. Whilst the implications of intercellular adhesion molecule-
      upregulation in asthma remain to be fully elucidated, its participation in cell
      trafficking and activation are being considered as a target for treatment. We
      present here early attempts to interfere with intercellular adhesion molecule-1
      as an adhesion molecule involved in cell influx and studies aimed preventing
      virus-induced exacerbations of asthma in children based on the knowledge that
      intercellular adhesion molecule-1 is the receptor for rhinoviruses.

PMID- 9623704
TI  - Plasma-derived proteins in airway defence, disease and repair of epithelial
      injury.
AB  - One significant characteristic of the airway mucosa in vivo, that cannot easily
      be mimicked in vitro, is its microcirculation, which generates a highly dynamic,
      biologically active milieu of plasma-derived molecules that may pass to the
      airway lumen in vivo. New data on the mechanisms of airway mucosal exudation
      indicate that the protein systems of circulating plasma may contribute
      significantly to the biology and immunology of the lamina propria, its surface
      epithelium and the luminal surface, not only in injured airways, but also in
      airways that are activated but display no sign of oedema, epithelial disruption,
      or increased absorption capacity. We suggest that present knowledge of the
      mechanisms of plasma exudation, together with rapidly emerging information (not
      detailed herein) on receptors, target cells and cellular responses to the plasma
      derived molecules, must be considered in any realistic model that investigates
      "immuno-inflammatory" mechanisms of the airway mucosa.

PMID- 9623705
TI  - Possible recurrence of desquamative interstitial pneumonitis in a single lung
      transplant recipient.
AB  - Idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis) is a disorder
      with a very poor prognosis for patients who do not respond to therapy with
      corticosteroids alone or in combination with immunosuppressive drugs, e.g.
      cyclophosphamide or azathioprine. For patients with end-stage disease, lung
      transplantation remains the only possibility for long-term survival. We describe
      a patient who received a left single lung transplant for end-stage desquamative
      interstitial pneumonitis. One year later, the patient again began complaining of
      exertional dyspnoea and a gradual decline in the transfer factor of the lung for
      carbon monoxide (TL,CO) was apparent. A recurrence of the primary disease in the
      transplanted lung was suspected on transbronchial biopsies. During treatment with
      high doses of steroids, a Pneumocystis carinii pneumonia developed, which was
      treated with co-trimoxazole. The patient completely recovered and, after a period
      of over 2 yrs, remained in an excellent condition, after which time he was lost
      from follow-up.

PMID- 9623706
TI  - Pulmonary infection due to Mycobacterium szulgai, case report and review of the
      literature.
AB  - We describe the case of a patient with a chronic pulmonary infection due to a
      mycobacterium tentatively identified as Mycobacterium flavescens, but finally
      shown to be Mycobacterium szulgai; this is the first M. szulgai infection
      reported in Italy. The patient responded to treatment with multiple
      antituberculosis drugs only after two cycles of 10 and 6 months, respectively.
      The literature concerning previous case reports in which M. szulgai is involved
      is revised and the difficulty concerning the identification of this rare
      mycobacterium, along with its in vitro and in vivo susceptibility, are discussed.

PMID- 9623707
TI  - Bronchial manifestation of acute febrile neutrophilic dermatosis (Sweet's
      syndrome).
AB  - We describe a 62 yr old female with acute febrile neutrophilic dermatosis (AFND)
      or Sweet's syndrome, involving the bronchial mucosa. The patient presented with
      classical skin manifestations of AFND accompanied by bilateral pneumonia, pleural
      effusions and lesions of the oral mucosa. The diagnosis was confirmed by skin and
      mucosal biopsies. Bronchoscopy revealed raised pustules, similar to the lesions
      of the skin, suggesting bronchial involvement of AFND. The patient responded to
      systemic corticosteroids only for a short period and died as a result of
      multiorgan failure. Postmortem findings confirmed dense, focal neutrophilic
      infiltrates of the bronchi and bronchioles. No underlying disease was found.

PMID- 9623708
TI  - An opacity in the chest following a subclavian catheterization.

PMID- 9623709
TI  - ERS Task Force Report. Guidelines for management of adult community-acquired
      lower respiratory tract infections. European Respiratory Society.

PMID- 9623710
TI  - Air pollution and daily admissions for chronic obstructive pulmonary disease in
      six European cities: results from the APHEA project. Air Pollution and Health, a
      European Approach.

PMID- 9623711
TI  - Gas exchange in acute COPD exacerbation.

PMID- 9623712
TI  - The priority for recognizing asbestos as a multicentre carcinogen, and problems
      in categorizing asbestos tumours.

PMID- 9623713
TI  - Roles of chemical mediators in the taste system.
AB  - Recent advances in neural mechanisms of taste are reviewed with special reference
      to neuroactive substances. In the first section, taste transduction mechanisms of
      basic tastes are explained in two groups, whether taste stimuli directly activate
      ion channels in the taste cell membrane or they bind to cell surface receptors
      coupled to intracellular signaling pathways. In the second section, putative
      transmitters and modulators from taste cells to afferent nerves are summarized.
      The candidates include acetylcholine, catecholamines, serotonin, amino acids and
      peptides. Studies favor serotonin as a possible neuromodulator in the taste bud.
      In the third section, the role of neuroactive substances in the central gustatory
      pathways is introduced. Excitatory and inhibitory amino acids (e.g., glutamate
      and GABA) and peptides (substance P and calcitonin gene-related peptide) are
      proved to play roles in transmission of taste information in both the brainstem
      relay and cortical gustatory area. In the fourth section, conditioned taste
      aversion is introduced as a model to study gustatory learning and memory.
      Pharmacobehavioral studies to examine the effects of glutamate receptor
      antagonists and protein kinase C inhibitors on the formation of conditioned taste
      aversion show that both glutamate and protein kinase C in the amygdala and
      cortical gustatory area play essential roles in taste aversion learning. Recent
      molecular and genetic approaches to disclose biological mechanisms of gustatory
      learning are also introduced. In the last section, behavioral and pharmacological
      approaches to elucidate palatability, taste pleasure, are described. Dopamine,
      benzodiazepine derivatives and opioid substances may play some roles in
      evaluation of palatability and motivation to ingest palatable edibles.

PMID- 9623714
TI  - Cerebral vasodilators.
AB  - The vascular tone, vascular resistance and blood flow in the brain are regulated
      by neural and humoral factors in quite a different way from those of peripheral
      organs and tissues. In contrast to the dominant vasoconstrictor control in the
      periphery, the intracranial vascular tone is predominantly influenced by
      vasodilator mediators over vasoconstrictor ones. Recent studies have revealed
      that nitroxidergic vasodilator nerve and endothelium-derived hyperpolarizing
      factor (EDHF) or K+ channel opening substance appear to play important roles in
      the regulation of cerebral arterial and arteriolar tone in primate and subprimate
      mammals, in addition to the accepted information concerning the crucial
      contribution of endothelium-derived relaxing factor (EDRF) or nitric oxide (NO),
      polypeptides, prostanoids, etc. This article summarizes characteristic properties
      of vasodilator factors in controlling the cerebral arterial and arteriolar tone
      that undoubtedly contribute to circulatory homeostasis. The content includes
      vasodilator nerve, endogenous vasodilator substances, and vasodilator
      interventions such as hypoxia, hypercapnia and hyperosmolarity.

PMID- 9623715
TI  - Effects of azelnidipine, a dihydropyridine calcium antagonist, on myocardial
      stunning in dogs.
AB  - Effects of azelnidipine, a dihydropyridine derivative, on stunned myocardium were
      examined in anesthetized open-chest dogs. The left anterior descending (LAD)
      coronary artery was ligated for 20 min and then released for 60 min. Dimethyl
      sulfoxide (DMSO), the solvent of azelnidipine, or azelnidipine (0.03, 0.1 or 0.3
      mg/kg) was injected i.v. 20 min before ligation. Segment shortening was
      determined by sonomicrometry. The levels of high-energy phosphate were measured
      in 60-min reperfused hearts. Azelnidipine at 0.1 and 0.3 mg/kg significantly
      decreased diastolic blood pressure and increased % segment shortening. The
      increase in % segment shortening due to azelnidipine appeared to be abolished by
      propranolol and atropine pretreatment. Ischemia significantly decreased % segment
      shortening in all groups. The % segment shortening that had been decreased by
      ischemia recovered during reperfusion, but did not reach its preischemic level in
      each group. In the 0.1 and 0.3 mg/kg of azelnidipine-treated dogs, a significant
      enhancement of % segment shortening recovery during reperfusion was observed, as
      compared with that in the DMSO-treated dogs. Azelnidipine did not affect the high
      energy phosphate levels in 60-min reperfused hearts. In conclusion, azelnidipine
      improved the contractile dysfunction in stunned myocardium, without any
      preservation of high-energy phosphate.

PMID- 9623716
TI  - Cytotoxic actions of FTY720, a novel immunosuppressant, on thymocytes and brain
      neurons dissociated from the rat.
AB  - Effects of FTY720 (2-amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol HCl), a
      novel immunosuppressant, were examined on neurons and thymocytes respectively
      dissociated from rat brains and thymus glands using a flow cytometer to see if
      FTY720 exerts cytotoxic actions not only on spleen cells as previously reported
      but also on the other cells. FTY720 at a concentration of 10 microM deteriorated
      almost all of the thymocytes, while it was not the case for brain neurons. FTY720
      increased the intracellular concentration of Ca2+ ([Ca2+]i) of thymocytes in both
      the presence and absence of external Ca2+, although the [Ca2+]i increased by
      FTY720 in the presence of external Ca2+ was much greater than that in the absence
      of external Ca2+. Thus, FTY720 may increase the membrane permeability of Ca2+ and
      release Ca2+ from intracellular Ca2+ stores in thymocytes. Furthermore, the
      number of thymocytes stained with ethidium, a dye impermeant to intact membranes,
      time-dependently increased after drug application. Therefore, FTY720 at
      concentrations of 3 - 10 microM non-specifically increases the membrane
      permeability of thymocytes, resulting in necrotic cell death, although FTY720 at
      micromolar concentrations was reported to induce apoptosis of spleen cells.

PMID- 9623717
TI  - Inhibition by gamma-aminobutyric acid system activation of epileptic seizures in
      spontaneously epileptic rats.
AB  - The effects of muscimol, a gamma-aminobutyric acid (GABA)A-receptor agonist, and
      aminooxy-acetic acid (AOAA), an inhibitor of GABA-converting enzyme, on tonic and
      absence-like seizures in spontaneously epileptic rats (SER: zi/zi, tm/tm) were
      investigated to elucidate whether GABAergic function operates normally in these
      animals. Muscimol at doses of 1 and 3 mg/kg (i.p.) induced high-voltage slow
      waves in the cortical and hippocampal EEG of SER, although the behavioral
      observation suggested inhibition of absence-like seizures. Similar high-voltage
      slow waves were also observed in the cortical and hippocampal EEG of normal rats
      with muscimol (1 and 3 mg/kg). Tonic convulsions in SER were dose-dependently
      inhibited by muscimol. AOAA (3 and 10 mg/kg, i.v.) inhibited both tonic and
      absence-like seizures in SER, although there were no obvious changes in EEG
      pattern. The inhibitory effects of AOAA on tonic convulsions appeared more slowly
      and lasted longer than those on absence-like seizures. Cerebral, hippocampal and
      cerebellar GABA levels were significantly higher in SER than the normal
      Kyo:Wistar and zitter rat (zi/zi), which were both the parent strains. These
      findings suggest that GABA receptors and GABAergic neurons are functional in SER
      and that the GABA system is involved in the inhibition of both seizures.

PMID- 9623718
TI  - Effects of dermatan sulfate, a heparin cofactor II mediated thrombin inhibitor,
      on the endotoxin-induced disseminated intravascular coagulation model in the rat:
      comparison with low-molecular weight heparin, nafamostat mesilate and
      argathroban.
AB  - Effects of dermatan sulfate (DS) on the endotoxin-induced disseminated
      intravascular coagulation (DIC) rat model were compared with those of low
      molecular weight heparin (LMWH), nafamostat mesilate (NM) and argathroban (AR).
      At doses of 5, 10 or 20 mg/kg/4 hr, DS significantly ameliorated the decrease of
      fibrinogen (Fbg), the increase of fibrin-fibrinogen degradation products (FDP)
      and except at the highest dose (20 mg/kg/4 hr), the prolongation of thrombin
      clotting time (TCT). It also decreased the glomerular fibrin deposits (%GFD) at
      doses of 10 or 20 mg/kg/4 hr. LMWH suppressed the decrease of Fbg and the
      increase of FDP at doses of 1.4 or 2.8 mg/kg/4 hr. Only the highest dose of LMWH
      suppressed the decrease of the platelet count (PL), the prolongation of
      prothrombin time, and improved the %GFD. AR suppressed the decrease of PL and
      improved the %GFD. At the dose required to improve the %GFD, DS (5, 10 mg/kg/4
      hr) significantly suppressed the prolongation of TCT, which is related to the
      bleeding frequency, while LMWH and AR further increased the prolongation of the
      TCT. These results suggest that DS has potential as a therapeutic drug with a
      lower hemorrhagic risk as compared with LMWH and AR in the treatment of DIC.

PMID- 9623720
TI  - Does binding of ouabain to human alpha1-subunit of Na+, K+-ATPase affect the
      ATPase activity of adjacent rat alpha1-subunit?
AB  - To ascertain whether ouabain binding to human alpha1-subunit influences
      coexpression of rat alpha1-subunit, the ouabain-sensitive profiles of Na+,K+
      ATPase activity and 86Rb+ uptake activity and ouabain binding capacity were
      measured in HeLa cells stably expressing rat alpha1-subunit. The ouabain
      sensitive profile of ATPase and 86Rb+ uptake activity seemed to be the sum of two
      components, one with high and one with low apparent affinity to ouabain, which
      were similar to that observed in HeLa and NRK-52E cells derived from human and
      rat, respectively. The ATPase activity with low sensitivity to ouabain increased
      in simple proportion to the amount of the rat alpha1 mRNA derived from
      transfected cDNA, which was determined by the reverse transcription-polymerase
      chain reaction method. The turnover number of the human Na+,K+-ATPase activity
      obtained from the ratio of the Na+,K+-ATPase activity to the ouabain binding
      capacity is about 150/sec. The expression of the rat alpha1-subunit had no effect
      on the turnover numbers of the Na+,K+-ATPase activity with high affinity to
      ouabain estimated from the ouabain binding capacity as the active site
      concentration. These results suggested that the ouabain bound to human alpha1
      subunit did not inhibit the ATPase activity of the coexpressing rat alpha1 in
      these cells.

PMID- 9623719
TI  - Effects of in vitro and in vivo exposure to doxorubicin (adriamycin) on caffeine
      induced Ca2+ release from sarcoplasmic reticulum and contractile protein function
      in 'chemically-skinned' rabbit ventricular trabeculae.
AB  - Doxorubicin is an anthracycline antibiotic that is used widely as a
      chemotherapeutic agent. However, the usefulness of this agent is limited due to
      its cardiotoxic effects. The mechanisms associated with this cardiotoxicity
      remain essentially unknown, despite numerous studies describing a range of
      structural and functional abnormalities. The purpose of the present study was to
      determine the in vivo and in vitro effects of doxorubicin exposure on
      sarcoplasmic reticulum (SR) Ca2+-content and contractile protein function. The
      Ca2+-content of SR is shown to have a biphasic response to in vivo and in vitro
      doxorubicin exposure that is time- and dose-dependent. In vitro doxorubicin
      exposure initially reduces the SR Ca2+-content, but the predominant action to
      block the SR Ca2+-release channel increases SR Ca2+-content within 60 min.
      Similar results are observed with in vivo doxorubicin exposure: it leads to Ca2+
      overload. These data are consistent with the view that doxorubicin acts in a
      similar manner to ryanodine and results in cardiomyopathy due to Ca2+-overload.

PMID- 9623721
TI  - Role of nitric oxide in the convulsions following the coadministration of
      enoxacin with fenbufen in mice.
AB  - Effects of nitric oxide (NO) synthase inhibitors on the enoxacin-induced
      convulsions were examined in mice pretreated with fenbufen. 7-nitroindazole
      markedly suppressed the incidence of convulsions, whereas L-arginine did not
      modify the convulsions at all. The suppression of the convulsions by 7
      nitroindazole was not reversed by the pretreatment of L-arginine. Brain NO
      synthase activity was significantly raised at 30 min after enoxacin when combined
      with fenbufen. The increased NO synthase activity was found to be suppressed by
      the pretreatment of 7-nitroindazole. These findings suggest that endogenous NO
      may be involved as a proconvulsant substance in the development of enoxacin
      induced convulsions in mice pretreated with fenbufen.

PMID- 9623722
TI  - Role of bradykinin in the reduction of left ventricular hypertrophy induced by
      angiotensin-converting enzyme inhibitors in spontaneously hypertensive rats.
AB  - We examined the effects of icatibant, a specific bradykinin B2-receptor
      antagonist, on the regression of left ventricular mass (LVM) induced by
      angiotensin converting enzyme (ACE) inhibitors, ramipril and imidapril, in
      spontaneously hypertensive rats. Both ramipril and imidapril lowered blood
      pressure equally, which were not influenced by icatibant. Icatibant did not alter
      the regressive effect of imidapril, while it showed a tendency to increase LVM in
      the ramipril-treated rats. The changes of LVM induced by icatibant were
      significantly different between the ramipril- and the imidapril-treated rats,
      suggesting that the role of bradykinin in the antihypertrophic effect might
      differ among ACE inhibitors.

PMID- 9623723
TI  - Different chronotropic and inotropic effects of EMD 57033 and EMD 53998, Ca2+
      sensitizers, on isolated, blood-perfused dog heart preparations.
AB  - To investigate whether a Ca2+ sensitizer increases sinus rate, we studied the
      effects of racemic thiadiazinone, EMD 53998 (a Ca2+ sensitizer with
      phosphodiesterase inhibitory action) and its (+)-enantiomer EMD 57033 (a
      relatively pure Ca2+ sensitizer) on isolated, blood-perfused spontaneously
      beating right atria and paced left ventricles of the dogs. EMD 53998 increased
      sinus rate dose-dependently, but EMD 57033 did not. Both substances increased
      atrial and ventricular contractile force. Propranolol did not affect the
      responses to each substance. These results suggest that the Ca2+ sensitizing
      action induced by EMD 57033 does not affect pacemaker currents directly.

PMID- 9623724
TI  - Neuroprotective effect of YM-39558, orotic acid ethylester, in gerbil forebrain
      ischemia.
AB  - We studied the effects of orotic acid and YM-39558 (2,6-dioxo-1,2,3,6
      tetrahydropyrimidine-4-carboxylic acid ethyl ester), orotic acid ethylester, on
      delayed neuronal death of hippocampal CA1 neurons induced by transient forebrain
      ischemia. Our data indicated that YM-39558 had high permeability across the blood
      brain barrier and was hydrolyzed to orotic acid, the active substance, in the
      brain. The neuronal damage was reduced significantly in animals intraperitoneally
      treated with YM-39558 (100 mg/kg x 3) after ischemia, but not with orotic acid in
      the same way. The results also suggested that the maintenance of a few ten
      micromolar orotic acid in cerebrospinal fluid were needed for its neuroprotective
      effects.

PMID- 9623725
TI  - Regulation of HLA-DR and costimulatory B7 molecules in human thyroid carcinoma
      cells: differential binding of transcription factors to the HLA-DRalpha promoter.
AB  - The consequence of autoantigen presentation by thyroid cells is dependent on the
      magnitude of expression of both HLA class II antigens (mainly HLA-DR) and
      costimulatory molecules, such as B7 (CD80 and CD86). Autoimmune thyrocytes are
      induced to express HLA-DR by interferon-gamma (IFN-gamma). The costimulatory
      signal leading to autoantibody production or cytotoxic T-cell immune response
      could be provided by antigen presenting cells (APCs) attracted to the thyroid by
      the primary autoimmune stimulus. Malignant thyrocytes can express HLA-DR antigens
      either constitutively, as a result of a nonimmunologic stimulus, or on induction
      with IFN-gamma after triggering of an immune response. However, their ability to
      express B7 molecules, which may determine enhanced antitumoral immune response
      mainly in the absence of intrathyroidal macrophages, has not yet been studied.
      The regulation of HLA-DR gene expression in APCs, such as B cells, is mediated by
      a series of short DNA consensus sequences located in the promoter, termed the W,
      X, and Y boxes, which bind several known transcription factors. We have
      previously characterized the expression of HLA-DR in four human thyroid carcinoma
      cell lines and found differences between constitutive and high- or moderate
      induced expression of the protein and mRNA. Evaluation of B7 expression on the
      surface of thyroid cancer cells and understanding the mechanisms of HLA-DR gene
      expression may help in designing efficient immune response to thyroid tumors.
      Using the electrophoretic mobility shift assay (EMSA), we have demonstrated
      differences between the four thyroid cell lines in the binding of transcription
      factors to each of the three boxes. The binding to the promoter in each of the
      cell lines resulted in a single band, probably representing a complex of proteins
      formed via protein-protein interactions. Using flow cytometry we have shown that
      the B7 molecule was absent in the four thyroid cell lines and could not be
      induced by IFN-gamma. The absence of surface B7 molecules from the malignant
      thyroid cells may lead to either suppression of antitumoral cytotoxic T cell
      response or demand the cooperation of infiltrating APCs to favor immune response.
      Differences previously found in HLA-DR expression in the four human malignant
      thyroid cell lines may be explained by the variation in the binding of
      transcription factors to the boxes in the HLA-DRalpha promoter. The binding
      patterns of nuclear proteins derived from the four thyroid cell lines or from the
      B lymphocyte cell line--Raji--to each of the boxes or to the whole promoter
      exhibit similarities, thus suggesting similar DNA-protein interactions.

PMID- 9623726
TI  - Interleukin-6 levels are not increased in women with postpartum thyroid
      dysfunction.
AB  - Postpartum thyroid dysfunction (PPTD) is an autoimmune-mediated thyroid
      destructive process. Human interleukin-6 (IL-6) is a cytokine found to be
      increased in subacute thyroiditis, amiodarone-induced thyrotoxicosis, Graves'
      disease, and other thyroid destructive processes. We report serum IL-6 levels in
      PPTD in two independent studies. New York Study: In a previous prospective study
      we demonstrated that PPTD occurred in 25% (7/28) of women with type 1 diabetes
      mellitus. IL-6 determinations were made on the frozen serum samples of these 28
      women during each trimester of their pregnancy and at 1.5, 3, 6, 9, and 12 months
      postpartum. IL-6 levels were found to be similar in women with PPTD compared with
      women without PPTD (mean 3.06+/-2.25 vs. 2.51+/-2.21 pg/mL; p = 0.15). No
      difference in IL-6 levels was found between the pre- and the postpartum periods
      (mean 2.67+/-1.82 vs. 3.04+/-2.44 pg/mL; p = 0.30) in all 28 women. Cardiff
      Study: Serum IL-6 levels were measured on frozen serum samples of 30 women with
      PPTD. IL-6 levels were below the detection limit (25 fmol/L or 0.65 pg/mL) in 94
      (67%) of these samples. No significant difference in the mean serum IL-6 levels
      were found between any time points in the study. There was no correlation between
      serum IL-6 levels, thyroid peroxidase (TPO)- antibodies and serum thyrotropin
      (TSH) levels at any time point. IL-6 levels during pregnancy or postpartum were
      not found to be significantly different in women with PPTD compared with women
      without PPTD.

PMID- 9623727
TI  - Clinical features associated with an increased risk of thyroid malignancy in
      patients with follicular neoplasia by fine-needle aspiration.
AB  - The application of fine-needle aspiration (FNA) to the evaluation of the thyroid
      nodule has greatly enhanced the ability of the clinician to appropriately select
      patients for thyroidectomy. However, despite extensive experience with thyroid
      FNA, the cytological distinction of benign from malignant follicular neoplasia
      remains problematic. As a result, most patients with FNA findings of a follicular
      neoplasm are referred for thyroidectomy. The goal of the present study was to
      develop clinical criteria capable of predicting malignancy in patients with an
      FNA diagnosis of follicular neoplasm. Among 1121 patients undergoing thyroid FNA
      at two large teaching centers during the period 1990 to 1995, 149 patients had
      cytological findings consistent with a follicular neoplasm. Among 103 patients
      referred for thyroidectomy, 22 (21%) were found to have a malignancy in the
      biopsied nodule. Among patients subjected to thyroidectomy, the risk of
      malignancy was significantly higher when follicular neoplasia was present in a
      male (43% vs. 16% for females, p = 0.007), when the nodule was greater than 4 cm
      to palpation (40% vs. 13% for nodules less than 4 cm, p = 0.03), or when the
      nodule was judged to be solitary by palpation (25% vs. 6% for a dominant nodule
      in a multinodular goiter, p = 0.02). Bayesian analysis of the data reveals that
      after an FNA showing a follicular neoplasm, the risk of malignancy in males with
      large nodules was nearly 80%, compared with a rate of only 3% in females with
      small nodules. These results suggest that clinical features including gender,
      nodule size, and character of the gland by palpation can be systematically
      integrated into the decision analysis, thereby improving the selection of
      patients for surgical referral.

PMID- 9623728
TI  - Clinical forms of presentation and evolution of diffuse sclerosing variant of
      papillary carcinoma and insular variant of follicular carcinoma of the thyroid.
AB  - We investigated whether the diffuse sclerosing variant of papillary carcinoma
      (diffuse sclerosing PC) and insular carcinoma (IC), two different subforms of
      differentiated carcinoma of the thyroid gland, have different clinical behaviors
      and prognosis in order to select appropriate therapy. The characteristics of
      clinical presentation, and outcome after therapy were evaluated in a series of
      113 patients (18 males and 95 females) with differentiated thyroid carcinoma
      treated with the same protocol, of which 7 had diffuse sclerosing PC and 6 had
      IC; within this series, patients with diffuse sclerosing PC and IC were compared
      with 76 cases of papillary carcinoma (PC) and 24 cases of follicular carcinoma
      (FC), respectively. Diffuse sclerosing PC patients were younger (23+/-9 vs. 38+/
      16 years) and had a higher degree of lymphatic metastases at diagnosis (100%)
      than patients with PC (47%). Five of 7 patients with diffuse sclerosing PC were
      alive and without evidence of disease compared to 34 of 76 patients with PC at
      follow-up (6.4+/-5.1 and 7.9+/-7 years, respectively). No prognostic differences
      were found between them. IC showed a more advanced stage of disease at diagnosis
      and a more aggressive clinical course with a higher percent of metastases and
      mortality than patients with FC at follow-up (1 patient died and 5 were alive
      with persistent disease at 4.8+/-3.7 years for IC; 22 were alive, 13 of them with
      persistent disease; and 2 died at 8.4+/-5.3 years for FC). We conclude that
      patients with diffuse sclerosing PC do not require a different treatment than
      that given to PC patients, while in contrast, IC cases need a more aggressive
      therapeutic approach.

PMID- 9623729
TI  - Observer variation in the clinical and laboratory evaluation of patients with
      thyroid dysfunction and goiter.
AB  - Three endocrinologists assessed thyroid function (hypothyroid, possibly
      hypothyroid, euthyroid, possibly hyperthyroid, or hyperthyroid), thyroid size
      (small, medium, or large), thyroid type (diffuse, nodular, or solitary nodule),
      and diagnosis and treatment options in 55 patients (47 women and 8 men) with a
      median age of 43 years (range 19 to 74) suspected of thyroid disease. The
      observers were presented stepwise for the (1) patient, clinical examination, and
      patient history; (2) blood tests; (3) 99mTc-pertechnetate scintigraphy; and (4)
      ultrasonography. The reproducibility was assessed by means of the K coefficient.
      Compared with evaluation of the patient alone, agreement on thyroid dysfunction
      was almost perfect when the results of the blood tests were known. The K values
      for pairs of observers rose significantly from 0.55 to 0.65 to 0.88 to 0.93. All
      three observers altered their opinion as to thyroid dysfunction in one third of
      the patients when the blood tests were known. Compared with evaluation of the
      patient alone, agreement on the morphology of the thyroid gland did not improve
      significantly in spite of access to thyroid scintigraphy; with the addition of
      thyroid ultrasound, agreement improved significantly for some pairs of observers.
      The three observers agreed on the rough estimate of thyroid size in only 36% of
      the patients. When all information was available, the three observers agreed on
      diagnosis and treatment category in 60% of the patients. Doctors should bear in
      mind the considerable observer variation when they evaluate patients with
      suspected thyroid disease.

PMID- 9623730
TI  - Acute suppurative thyroiditis with demonstrable distant primary focus: a report
      of two cases.
AB  - Two cases of acute suppurative thyroiditis occurring in a normal thyroid gland
      secondary to a demonstrable primary focus at a distant site are described and the
      role of interventional radiology in the management is discussed.

PMID- 9623731
TI  - The genetics of thyroid associated ophthalmopathy.

PMID- 9623732
TI  - The thyrotropin receptor in thyroid eye disease.
AB  - Thyroid eye disease (TED) has an autoimmune etiology, but the nature of the
      autoantigen that is the target of the initiating event remains unknown. A number
      of candidates have been proposed based on Western blotting, library screening,
      and deduction from sequence similarity. A strong favorite is the thyrotropin
      receptor (TSHR), which is the target of the thyroid stimulating antibodies (TSAB)
      of Graves' disease (GD). We have recently demonstrated TSHR transcripts in
      orbital adipose tissue from a patient with TED by Northern blot, transcripts in
      normal adipose tissue being at the limit of detection. We have shown that the
      transcripts are translated into protein by immunohistochemical analysis using two
      monoclonal antibodies to the TSHR generated by genetic immunization. TSHR
      immunoreactivity is associated with elongated cells with the appearance of a
      fibroblast, often adjacent to clusters of adipocytes, in orbital biopsies from
      patients with TED but not in strabismus or pseudotumor biopsies. In animal
      studies, we have transferred thyroiditis to naive BALBc and NOD mice, using T
      cells primed to the human TSHR, either using the receptor expressed as a
      bacterial fusion protein or by genetic immunization. The BALBc develop a Th2-type
      response to the receptor, but the NOD a Th1-type with thyrocyte destruction.
      Orbital pathology, edema, infiltration by mast cells and lymphocytes, and adipose
      accumulation was also induced in 68% of the BALBc but none of the NOD mice.
      Together these data indicate that the preadipocyte expresses the TSHR and that a
      Th2 autoimmune response to the receptor may be an initiating event in TED.

PMID- 9623733
TI  - Cytokines in thyroid eye disease: potential for anticytokine therapy.
AB  - Interactions between between orbital fibroblasts and immunocompetent cells that
      infiltrate or reside within the orbit are thought to be important in the
      pathogenesis of thyroid eye disease (TED). These interactions are mediated
      primarily by cytokines; interferon-gamma, tumor necrosis factor-alpha,
      interleukin-1alpha and leukoregulin are of particular interest in this regard.
      These mediators induce or enhance the in vitro expression of immunomodulatory
      proteins in orbital fibroblasts, and stimulate proliferative and metabolic
      activities of these cells. The stimulation by particular cytokines of
      glycosaminoglycan synthesis in orbital fibroblasts is an important factor in the
      development of the clinical disease. A similarly important pathophysiological
      role for cytokines has been defined in rheumatoid arthritis. In this disease, the
      chronic erosive changes in the cartilage and bone of the joints result from
      cytokine-stimulated production of collegenases and other neutral proteases by
      synovial cells and articular chondrocytes. Advances in the understanding of the
      pathogenesis of rheumatologic joint disease has led to treatment trials aimed at
      immune-modulation, including trials of anticytokine therapy. Lessons learned in
      early clinical trials using these biological therapies in the treatment of
      rheumatoid arthritis can be applied to studies of similar agents in the treatment
      of TED.

PMID- 9623734
TI  - T-cell restriction in thyroid eye disease.
AB  - Infiltrating immunocompetent cells act to establish and perpetuate the orbital
      autoimmune process in thyroid eye disease (TED). Until recently, it has remained
      unclear whether T cells infiltrating the orbital connective/fatty tissue and
      extraocular muscles represent a primary immune response that is specifically
      directed against orbital antigens. In addition, despite a close clinical and
      temporal association of the thyroidal and extrathyroidal manifestations in
      Graves' disease (GD), it has not been proven whether T cells infiltrating
      thyroid, orbital, and pretibial tissue in patients with TED and pretibial
      dermopathy (PTD) are directed against certain antigenic determinants shared
      between these anatomically distinct tissues. Using polymerase chain reaction
      (PCR)-based molecular analysis of T-cell antigen receptor (TcR) variable (V)
      region genes, we have demonstrated marked restriction of orbital and pretibial
      TcR Valpha and Vbeta genes in patients with active TED and PTD. In addition,
      molecular analysis of T cells in paired samples of extraocular muscle and orbital
      connective/fatty tissue revealed usage of similar TcR V genes. In contrast, TcR V
      gene restriction was either absent or much less pronounced in patients with
      longstanding TED and PTD. Comparison of TcR V genes in T cells obtained from
      thyroid gland, orbital tissue, pretibial tissue, and peripheral blood of three
      individual patients with active GD, TED, and PTD also revealed marked restriction
      and, in addition, striking similarities of TcR V gene usage. Sequencing of
      complementarity determining regions 3 (CDR3) and junctional domains of TcR Vbeta
      genes confirmed oligoclonality of intrathyroidal, orbital, and pretibial T cells.
      Moreover, several conserved junctional motifs were shared by T cells infiltrating
      the thyroid gland and the extrathyroidal sites. Taken together, these data
      suggest that, in patients with GD and extrathyroidal manifestations, similar
      antigenic determinants may be responsible for recruitment and oligoclonal
      expansion of T cells both within the thyroid gland and in the involved
      extrathyroidal sites.

PMID- 9623735
TI  - Natural history of thyroid eye disease.

PMID- 9623736
TI  - Clinical presentation of thyroid associated orbitopathy.

PMID- 9623737
TI  - Glycosaminoglycans in thyroid eye disease.
AB  - Orbital accumulation of hydrophilic, interstitial glycosaminoglycans (GAG) and
      subsequent expansion of retrobulbar tissue lead to the clinical manifestation of
      exophthalmos in patients with thyroid eye disease (TED). In order to analyze
      whether the alteration of distribution pattern and biochemical composition of GAG
      and proteoglycans play a role in the development of the disease, a highly
      specific high-pressure liquid chromatography (HPLC) method was developed. The
      concentration of total GAG, chondroitin sulfate A (CA), dermatan sulfate (DS),
      and hyaluronic acid (HA) was determined in patients and controls, revealing
      marked differences in urinary concentration of total GAG and HA, as well as an
      elevation of CA in patients versus controls. Method sensitivity was 0.86 for
      patients with active disease, and 0.87 for patients with untreated
      ophthalmopathy, whereas specificity was 1.0 for patients with inactive disease.
      Patients with increased GAG concentration responded well to steroids and/or
      orbital irradiation. Furthermore, distribution pattern of orbital extracellular
      matrix GAG exhibited a significant increase in the tissue fractions of CA and HA
      in patients with TED in comparison to controls. In conclusion, GAG
      polysaccharides not only play a major role in the pathogenesis of TED but have
      been successfully introduced as an activity marker of the disease.

PMID- 9623738
TI  - Octreotide scintigraphy in thyroidal and orbital Graves' disease.

PMID- 9623739
TI  - Relation between thyroid eye disease and type of treatment of Graves'
      hyperthyroidism.

PMID- 9623740
TI  - Orbital radiotherapy for Graves' ophthalmopathy.

PMID- 9623741
TI  - Somatostatin analogues in the treatment of thyroid eye disease.
AB  - Recent studies have shown successful therapy with the long-acting somatostatin
      (SM) analogues octreotide and lanreotide in patients with thyroid eye disease
      (TED). In one such study it was also found that response to low-dose octreotide
      treatment (300 microg) in these patients was correctly predicted by [111In-DTPA-D
      Phe1]-octreotide scintigraphy and concluded that this parameter should be used as
      a predictive test of the effectiveness of treatment with nonradioactive
      octreotide. It has also been suggested that octreoscan-111 may be seen as a
      parameter of disease activity in TED. However, it remains to be clarified whether
      octreoscan-111 predicts the therapeutic outcome better than the clinical activity
      score, or magnetic resonance imaging (MRI) or finally measurement of
      glucosaminoglycan (GAG) in the plasma and/or urine. The exact mechanism of action
      of SM analogues has not yet been fully clarified. Three explanations may be
      offered. First, SM suppresses insulin-like growth factor 1 (IGF-1) activity and
      inhibits IGF-1-mediated effects. A second possible mechanism could be the direct
      inhibition of the release of cytokines from T-lymphocytes, and finally, SM
      analogues may act on target cells through specific cell surface receptors. In
      view of the encouraging therapeutic results reported thus far in several studies,
      SM analogues may provide a valuable therapeutic alternative to corticosteroids,
      especially in patients who cannot tolerate the latter. However, further
      prospective, placebo-controlled studies with a large number of patients are
      needed before we can reach final conclusions.

PMID- 9623742
TI  - Surgical treatment of thyroid eye disease.
AB  - Thyroid eye disease may result in exophthalmos, diplopia, and eyelid
      malpositions, which can be corrected with different surgical procedures. Several
      techniques for decompressing the orbit have been described, and the advantages
      and disadvantages of the techniques are discussed. Our own results of the
      transantral approach are briefly summarized. Eye muscle surgery should be
      performed after an orbital decompression, and it is not unlikely that more than
      one muscle operation will be needed in order to achieve single vision. A number
      of operative procedures for eyelid surgery have been described, and the results
      of the various methods are generally good.

PMID- 9623743
TI  - Prevention of thyroid eye disease and final conclusions.

PMID- 9623744
TI  - Concurrent validity of the MMPI-A in a counseling program for juvenile offenders.
AB  - This study was conducted to examine the concurrent validity of the MMPI-A
      (Minnesota Multiphasic Personality Inventory-Adolescent) in an adolescent
      offender setting. From a sample of 50 court-adjudicated youths participating in
      an outpatient counseling program, 42 valid MMPI-A profiles were obtained, 33 of
      which were accompanied by counselor ratings of behavior problems. The highest
      mean elevations on the MMPI-A were on scales MAC-R (MacAndrew Alcoholism Scale
      Revised), A-Con (Adolescent Conduct Problems), A-Sch (Adolescent School
      Problems), Pd (Psychopathic Deviate), and IMM (Adolescent Immaturity). Counselor
      ratings of behavior problems correlated highly with scales ACK (Alcohol and Drug
      Acknowledgment Scale), A-Sch, A-Ang (Adolescent Anger Problems), Ma (Hypomania),
      and PRO (Alcohol/Drug Problem Proneness). This pattern of results supports the
      concurrent validity of the MMPI-A for use in this setting.

PMID- 9623745
TI  - The effects of physical and psychological well-being on suicidal ideation.
AB  - This study examines a theoretical model of suicidal ideation with physical
      symptoms (physical well-being) and self-esteem (psychological well-being) as two
      competitive predicting variables. The national sample of 1,433 cases was drawn in
      the People's Republic of China in March 1 995. Results indicate that both
      suicidal ideation and attempt rates are lower in the Chinese population than in
      other populations studied, and as found in the West, Chinese women are more
      likely to think about and to attempt suicide than Chinese men. LISREL analysis of
      the model shows that psychological well-being (self-esteem) is a much stronger
      predictor of suicidal ideation than physical well-being (physical symptoms),
      especially when depression is introduced as an intervening variable in the model.

PMID- 9623746
TI  - Diversity and attention deficit hyperactivity disorder.
AB  - Attention Deficit Hyperactivity Disorder (ADHD) is a debilitating disorder which
      affects children and adults in this country and around the world. Diversity
      variables such as ethnicity, age, gender, and socioeconomic status have been
      relatively neglected in ADHD research. Additionally, these variables have not
      traditionally been incorporated into clinical assessment, diagnosis, or
      intervention strategies. A review of the existing literature regarding diversity
      issues and ADHD was conducted, including a review of international findings.
      Implications for clinicians and researchers are incorporated.

PMID- 9623747
TI  - Inhibition of eating behavior: negative cognitive effects of dieting.
AB  - This study tested the hypothesis that dieters would score higher than nondieters
      in terms of food rumination. Two hundred and thirty one college undergraduates
      completed the Eating Obsessive-Compulsiveness Scale (EOCS) and responded to a
      questionnaire that inquired about dieting status. Subjects also completed
      measures that tapped neuroticism and social desirability. Results showed that
      current dieters were significantly more obsessed with thoughts of eating and food
      than were nondieters. Neither dieting status nor EOCS scale scores were related
      to neuroticism or social desirability. These results are consistent with previous
      theory and research suggesting that inhibition of appetitive behaviors can have
      negative cognitive effects. Moreover, they indicate a potential target for
      therapeutic intervention.

PMID- 9623748
TI  - Detecting feigned neuropsychological impairment with the Seashore Rhythm Test.
AB  - Sixty undergraduate subjects were randomly assigned to one of three groups and
      completed the Seashore Rhythm Test (SRT) as part of an investigation regarding
      simulated neuropsychological impairment. A sophisticated simulator group was
      instructed to feign impairment and was provided information regarding traumatic
      brain injury (TBI) sequelae. A naive simulator group was instructed to feign
      impairment, but was given no such information. A control group was instructed to
      perform optimally. Additionally, SRT scores for 20 TBI subjects who completed
      neuropsychological evaluations were analyzed. Mean SRT scores for the
      sophisticated and naive simulators did not differ but were significantly lower
      when compared to control subjects and TBI subjects. A discriminate function
      analysis cutting score correctly classified 79% of subjects, while classification
      rates obtained with two previously investigated cutting scores were 64% and 72%.
      Implications of using these cutting scores are discussed. The findings indicate
      the SRT is a useful indicator of feigned neurological impairment.

PMID- 9623749
TI  - Gender differences in factor structure of the Self-Administered Alcoholism
      Screening Test.
AB  - Recent studies have revealed differences between men and women alcoholics in
      symptoms, consequences, and help-seeking behavior related to alcohol usage. Based
      on these findings, it was hypothesized that gender differences also would appear
      on alcohol screening instruments. The Self-Administered Alcoholism Screening Test
      (Colligan, Davis, & Morse, 1988: SAAST: Swenson & Morse, 1975) of 1,920 men and
      1,775 women was subjected to a within-gender, principle-components, factor
      analysis with a varimax rotation. Gender differences at the component level were
      revealed. Men endorsed the "help-seeking for alcohol-related problems" component
      while women endorsed the "help-seeking for emotional problems" component. In
      addition, men expressed concern about receiving a psychiatric label while women
      expressed concern about receiving a drinker label. The results suggest that
      different items need to be used in screening women for alcohol-related problems.

PMID- 9623750
TI  - The factor structure of the Wechsler Adult Intelligence Scale-Revised: one or two
      but not three factors.
AB  - One-, 2-. and 3-factor solutions for the WAIS-R normative samples were examined
      using principal components analysis with varimax rotations. Factors were examined
      across age groups by computing congruence coefficients and root mean square
      differences to determine the equivalence and consistency of factors across age
      groups. There is strong evidence for the general (g) and 2-factor (verbal and
      perceptual organization) solutions but noticeably less support for memory/freedom
      from distractibility in the three-factor solution. Verbal and perceptual
      organization factors were also attenuated in the three-factor solution. One and 2
      factor solutions were essentially equally justifiable but because the 1-factor
      solution was weighted most heavily with verbal measures, the 2-factor solution
      may be advantageous because this solution does distinguish between verbal and
      performance measures.

PMID- 9623751
TI  - Clinical utility of the Test of Variables of Attention (TOVA) in the diagnosis of
      attention-deficit/hyperactivity disorder.
AB  - Ability of the Test of Variables of Attention (TOVA) to distinguish between
      referred children with attention-deficit/hyperactivity disorder (ADHD) and other
      (OTHER) clinical diagnoses were studied. The ADHD group differed from the OTHER
      group on TOVA variables and most measures from the Revised Conners Teacher Rating
      Scale (RCTRS) and ADD-H Comprehensive Teacher's Rating Scale (ACTeRS). The
      criteria of any one TOVA variable > 1.5 standard deviations from age and sex
      adjusted means correctly identified 80% of the sample with attention deficit
      disorders and 72% of the sample without attention deficit disorder. Cases
      misclassified by teacher ratings were often correctly classified by the TOVA and
      conversely. The TOVA makes a unique and important contribution to diagnostic
      evaluations.

PMID- 9623752
TI  - Factor structures of the Zung Self-Rating Depression Scale (SDS) for
      undergraduates.
AB  - In order to categorize the items of the Zung Self-Rating Depression Scale (SDS)
      so as to allow the construction of subscales, the Japanese version of the SDS was
      administered to a total of 2,258 undergraduates. Principal-component analyses of
      the SDS extracted three factors interpretable as cognitive, affective, and
      somatic symptoms. The SDS was then administered to 597 undergraduates in order to
      cross-validate the factor structures. The coefficient of congruence and the
      goodness-of-fitness index generated by a confirmatory factor analysis showed good
      cross-validity of the factor structures.

PMID- 9623753
TI  - The relationship between body dysmorphic disorder and depression, self-esteem,
      somatization, and obsessive-compulsive disorder.
AB  - The present study investigated the relationship of depression, self-esteem,
      somatization, and obsessive-compulsive disorder to the incidence of body
      dysmorphic disorder (BDD). Female (n=83) and male (n=25) undergraduates completed
      measures of body esteem, self-esteem, obsessive-compulsive behavior, and
      somatization. Subjects were also screened for eating disorders utilizing the DSM
      IV criteria for such in an effort to control for anorexia and bulimia. Upon
      excluding those subjects who met the criteria for eating disorders, the final
      sample included 78 females and 24 males. The results indicated that lower body
      esteem scores were linked with lower levels of self-esteem but with higher levels
      of obsessive-compulsive tendencies, depressive tendencies, and somatization
      tendencies. The findings are discussed with regard to the need for more accurate
      measures of body dysmorphic disorder, as well as etiology and future treatment
      implications.

PMID- 9623754
TI  - The positive family contribution of those with serious mental illness.
AB  - Fifty-five patients who met criteria for serious mental illness nominated a
      relative with whom they had lived for at least the previous 6 months to be sent a
      questionnaire that included a scale for rating patients' contribution to family
      life in 10 specific areas. Thirty-six relatives returned completed
      questionnaires. Patients rated their own contributions using the same scale.
      Overall, relatives rated patients' contributions as positive, and their ratings
      of patients when well generally agreed with patients' self-ratings. For women
      only, relatives rated contributions as significantly less when the patient was
      ill. Patients' self-rated level of psychological symptoms was the best predictor
      of relatives' overall satisfaction with them. Ratings of patients' contributions
      mirrored sex-role stereotypes.

PMID- 9623755
TI  - Assessment of locus of control in patients with anxiety and depressive disorders.
AB  - We studied Levenson's Internal (I), Powerful Others (P), and Chance (C) locus of
      control scales in 193 patients with six DSM-III-R diagnoses: Major Depression
      (MD), Panic Disorder (PD), Generalized Anxiety Disorder (GAD), Social Phobia
      (SP), Obsessive Compulsive Disorder (OCD), and Mixed Anxiety Depressive Disorder
      (MAD). Compared to the comparison groups (CG), we found specific patterns for
      some of the diagnostic categories. There were no significant differences between
      the I scale scores and of those in the different anxiety and depressive disorder
      groups and the CG. But, patients with MD, SP, or MAD had significantly higher P
      scale scores than the CG. Patients with MD, PD, SP, and MAD had higher C scale
      scores than the CG. The OCD patients had the lowest P and C scale scores of any
      of the groups and not significantly different than the CG. The findings have some
      research and clinical implications.

PMID- 9623756
TI  - Social desirability and the clinical self-report inventory: methodological
      reconsideration.
AB  - This study assesses how social desirability affects responses in clinical self
      report inventories. Six hundred items gathered from four normal personality
      questionnaires were adapted to devise a pre-experimental personality
      questionnaire (pre-EMHQ). Results obtained from administering Ko's Mental Health
      Questionnaire (KMHQ) and the pre-EMHQ to separate samples were the proportion of
      individuals answering "true" to each item (i.e., P(t)) and the social
      desirability scale value (i.e., SDSV) of each item. The Experimental Mental
      Health Questionnaire (EMHQ) was established from the pre-EMHQ by closely matching
      the P(t)s and the SDSVs of the two questionnaires. Administering the KMHQ and the
      EMHQ concurrently to another sample provided results for factor analysis and
      other statistical analyses. The SDSVs and the P(t)s for each of the KMHQ items
      certainly displayed a linearly increasing relation. The two sets of corresponding
      subscales also correlated significantly. By applying the polynomial regression
      analysis, the tendency to score might be expressed as a quadratic function of
      SDSVs. Two iterative principal-factor analyses of the two sets of subscales each
      resulted in two factors, and Factor 1 is similar in both the KMHQ and the EMHQ.
      In brief, social desirability plays a critical role in affecting responses in a
      clinical self-report inventory. The factors involved and suggestions proposed
      will be of value for further research.

PMID- 9623757
TI  - Areas of convergence and discordance between the MMPI-168 and the Reiss Screen
      for Maladaptive Behavior in mentally retarded clients.
AB  - The Reiss Screen for Maladaptive Behavior and a modified version of the MMPI-168
      were administered to 65 residents of a state mental institution diagnosed with
      mild or moderate mental retardation. Possible associations between the two
      screening instruments were then examined. Significant correlations were obtained
      between four scales of the Reiss Screen and Scales F, K, 1, 6, and 7 of the MMPI
      168. These results support the clinical efficacy of both instruments in screening
      for behavioral pathology in mentally retarded persons. However, some scales
      purported to assess similar psychological constructs failed to show expected
      positive associations.

PMID- 9623758
TI  - The Depression-Happiness Scale: reliability and validity of a bipolar self-report
      scale.
AB  - This article reports two studies aimed at validating the 25-item self-report
      McGreal and Joseph (1993) Depression-Happiness Scale (D-H S). In the first study,
      principal component data are reported on the D-H S with 194 respondents. A forced
      1-factor solution confirmed the unidimensionality of the scale (item loadings
      ranged from .38 to .77) and thus the feasibility of a statistically bipolar
      measure. In the second study, data on the convergent validity of the D-H S with
      the Beck Depression Inventory (r=-.75) and the Oxford Happiness Inventory (r=.59)
      with 100 respondents are reported confirming the construct validity of the scale.
      Implications for research in social and clinical psychology are discussed along
      with the possible uses of the D-H S in a clinical setting.

PMID- 9623759
TI  - The effect of voluntary eye movements on associations and mood.
AB  - The effects of eye movements induced by lights were compared to a non eye
      movement condition where subjects waited for a similar period of time. Subjects
      were first shown an emotional film which was interrupted just before its climax,
      and then exposed to 15 trials of 28-cycle eye movements or were exposed to the
      control waiting condition. After each trial they reported what they had thought
      about during the trial. Analysis of the themes and the depth of processing of
      these reports indicated that there was greater depth in the control than in the
      eye movement condition. There was little evidence of any effect on mood or
      emotional response, except that eye movements elicited greater hostile mood than
      the control condition.

PMID- 9623760
TI  - A novel tumor necrosis factor-alpha mutant with significantly enhanced
      cytotoxicity and receptor binding affinity.
AB  - A novel tumor necrosis factor-alpha mutant (mutant M3), in which Ser and Tyr at
      positions 52 and 56 were substituted by Ile and Phe, respectively, along with
      deletion of 7 N-terminal amino acids, was prepared and its biological activities
      were investigated. The mutant exhibited a 14- to 24-fold increase in the
      cytotoxicity relative to the wild-type TNF on various cancer cell lines. The
      binding affinity of the mutant to TNF-R55 and TNF-R75 receptors was over 10-fold
      higher than that of the wild-type. TNF-alpha and the mutant show similar CD
      spectra in the far-UV region, indicating that the overall structure was not
      influenced by the mutations. The production of highly potent TNF-alpha mutant
      utilizing increase of hydrophobicity in the region 52-56 may provide a structural
      basis for a design of optimized TNF-alpha as a therapeutic purpose.

PMID- 9623761
TI  - Spectroscopic studies of the interactions of the pyrethroid insecticide
      fenvalerate with gramicidin.
AB  - Fenvalerate is a pyrethroid insecticide which interacts with ionic channels.
      Using circular dichroism technique we have studied the interaction of fenvalerate
      with gramicidin, a model channel peptide which transports ions. In most organic
      solvents, gramicidin exists as a double helix except in trifluoroethanol where it
      exists as a channel forming single stranded beta6.3 helical monomer. In model
      lipid membranes, under certain experimental conditions, gramicidin exists as a
      channel forming single stranded beta6.3 helical dimer. Our results show that
      fenvalerate interacts more with the single stranded beta6.3 helical monomer or
      dimer than with the double helical form of gramicidin. This was further confirmed
      by an increase in the rate of gramicidin mediated proton transport in liposomes
      by fenvalerate, using the pH sensitive fluorophore, pyranine.

PMID- 9623762
TI  - Vaccinia virus-induced changes in cytokine-regulated acute phase plasma protein
      synthesis by hepatoma cells.
AB  - Human hepatoma cell line, HepG2, has been infected with vaccinia virus and
      synthesis of plasma proteins was determined by electroimmunoassay and
      corresponding mRNA's measured by Northern blotting. The inhibitory effect of the
      virus was dose- and time-dependent. Electrophoretic mobility shift assay revealed
      a decrease in C/EBP binding activities in nuclear extracts isolated from the
      infected hepatoma cells. Supershift analysis of the C/EBP isoforms showed alpha
      and beta subunit involvement in DNA binding. The treatment of the cells with
      interleukin-1, interleukin-6, and dexamethasone at the initial stage of infection
      appears to delay the virally induced inhibition of host cell protein synthesis.
      Thus, possible "protective" role of the acute phase cytokines in viral infection
      is proposed.

PMID- 9623763
TI  - The role of counterions in the interaction of bifunctional surface active
      compounds with model membranes.
AB  - Interaction of two series of bifunctional surfactants (bromides and chlorides)
      with red blood cells and planar lipid membranes was studied. The aim of the work
      was to determine the role of counterions in the mechanism of interaction of
      bifunctional cationic surfactants with model membranes. In each case bromides
      influenced model membranes to a greater degree than the corresponding chlorides.
      The possible explanation of the obtained results is presented. It seems that the
      greater ability of bromides to destabilize model membranes in comparison with
      chlorides can be attributed to the greater mobility and the smaller radius of the
      hydrated bromide ion. This may underlie the greater ease that this anion can
      modify the surface potential of the lipid bilayer, thus enhancing the interaction
      of the cationic surfactant with such a modified bilayer.

PMID- 9623764
TI  - The interaction of phospholipase A2 with liposomes: an immunological approach to
      its study.
AB  - Porcine pancreatic phospholipase A2 (PLA2) has been incubated for 2 hours at 34
      degrees C with rabbit anti-pig pancreatic PLA2 polyclonal antiserum in the
      absence or presence of phosphatidylcholine liposomes in different physical
      states. Subsequent assay of hydrolysis -triggered through addition of 5 mM Ca2+-
      at 34 degrees C, shows that preincubation with antiserum in the presence of 1,2
      dimyristoyl-3-sn-phosphatidylcholine liquid-crystalline vesicles, renders the
      PLA2 activity undetectable, similarly to what is found if preincubation is
      carried out in the absence of liposomes. In contrast, 1,2-dipalmitoyl-3-sn
      phosphatidylcholine liposomes, which at 34 degrees C are in the gel-phase,
      protect the enzyme from the antiserum effect. The results are consistent with a
      stronger binding of PLA2 to gel phase, as compared to liquid crystalline vesicles
      and suggest that through the physical interaction with liposomes in the gel
      state, the enzyme is shielded from reaction with the antibodies. Taking into
      account the characteristic hydrolysis profiles of vesicles in different physical
      states, it can be concluded that the above interpretation agrees with the
      proposal that PLA2-membrane association promotes the interfacial activation of
      the enzyme.

PMID- 9623765
TI  - Cecropin A - magainin 2 hybrid peptides having potent antimicrobial activity with
      low hemolytic effect.
AB  - In order to obtain peptides having improved antimicrobial activity with low
      hemolytic effect, a hybrid peptide (CA-MA) composed from cecropin A (1-8) and
      magainin 2(1-12), and its analogues with amino acid substitutions were designed
      and synthesized. The antimicrobial activities against bacterial cells and
      hemolytic activities against human red blood cells were analyzed for each
      peptide. Secondary structures of the peptides in aqueous solution, 50%
      trifluoroethanol, and sodium dodecylsulfate micelles were estimated using
      circular dichroism spectroscopy. The increase in hydrophobicity or alpha-helicity
      of the peptides correlated with an increase in hemolytic activity rather than
      antimicrobial activity. The substitution of Leu for Ser at position 16 in CA-MA
      resulted in a remarkable increase in antimicrobial activity without a significant
      change in hemolytic activity. Furthermore, the increase in antimicrobial activity
      of the peptides was not always accompanied by the increase in hemolytic activity.

PMID- 9623766
TI  - Resistance of the insulinotropic action of alpha-D-glucose and beta-L-glucose
      pentaacetates to cholera and pertussis toxins.
AB  - The pentaacetate esters of alpha-D-glucose and beta-L-glucose were recently
      reported to stimulate insulin release. The possible participation of G-protein
      coupled receptors to the insulinotropic action of these esters was investigated
      in rat pancreatic islets either preincubated with cholera toxin or obtained from
      animals injected with pertussis toxin. Neither procedure affected adversely the
      secretory response to the esters in islets incubated in the presence of L
      leucine. Thus, in both situations, alpha-D-glucose pentaacetate and, to a lesser
      extent, beta-L-glucose pentaacetate augmented insulin release evoked by the
      branched-chain amino acid, whilst beta-L-galactose pentaacetate failed to do so.
      These findings suggest that G-proteins sensitive to either cholera or pertussis
      toxins are not involved in one of the two modalities by which these esters are
      thought to stimulate insulin secretion, namely that independent of the catabolic
      fate of their hexose moieties.

PMID- 9623767
TI  - Variations in gene expression and genomic stability of human hepatoma cells
      integrated with hepatitis B virus DNA.
AB  - The association of hepatitis B virus (HBV) infection with human hepatoma is well
      established. However, no consensus regarding the etiology of hepatocellular
      carcinoma was elucidated. In this paper, the genomic stability and gene
      expression of HBV DNA-integrated and non-integrated hepatoma cells by Transcript
      Profile (TP)-PCR and RT-PCR are characterized. The additional DNA bands generated
      from TP-PCR of HBV integrated genomes were not correlated with the sequence of
      HBV, suggesting that the variations may result from genomic instability of the
      host cells. Moreover, differential genes expressed in HBV DNA-integrated cells
      were sequenced. A cDNA generated from the integrated cells exhibited 99.3%
      homology with the sequences of ATP synthase 6 and cytochrome C oxidase III, but
      the sequences were abnormally linked together. Since HBV infection may alter the
      energy metabolism of the cell, the results suggest that the integration may cause
      mitochondriae defects in the ATP synthase 6 and cytochrome C oxidase III genes.

PMID- 9623768
TI  - An extremely high conservation of RNA-protein S7 interactions during prokaryotic
      ribosomal biogenesis.
AB  - Direct determination of RNA-protein complex structures is often facilitated by
      the use of thermophilic proteins; however E. coli is the most investigated system
      so far. A hybrid approach is to form heterologous complexes of E. coli RNA with
      thermophilic proteins. The rationale for this approach to RNA-protein
      interactions in ribosomes is based on the ability of the thermophilic protein S7
      to replace a homologous counterpart in vivo. In vitro, the protein S7 of Thermus
      thermophilus is able to form complexes with both the minimal 16S rRNA fragment
      and the intercistronic region of the str operon mRNA from E. coli (Kd = 1.4 x
      10(7) M and 1.1 x 10(-7) M respectively). The interaction of Thermus S7 with the
      E. coli intercistronic mRNA is surprising, because this region does not exist in
      the thermophilic str operon. It suggests a high degree of conservation of an RNA
      binding site on S7.

PMID- 9623769
TI  - Amino acid residue 250 has a functional role in the assembly of rabbit liver
      microsomal cytochrome P450 2B4.
AB  - Cytochrome P450 2B4 lacking amino acids 2-27, CYP2B4 (delta2-27), was mutated at
      position 250 and expressed in E. coli fused to glutathione S-transferase.
      Expression of the E250S variant (holo- plus apoenzyme) proceeded to an extent
      comparable with that of CYP2B4 (delta2-27), while the protein level of the E250P
      mutant averaged 42% that of the control pigment. Comparison of these data with
      the corresponding reduced CO difference spectra of the various CYP2B4 (delta2-27)
      forms revealed that, in the control and E250S preparations, about 90% and 44%,
      respectively, of the total amount of hemoprotein present existed in the form of
      holoenzyme, whereas the E250P derivative failed to produce a reduced carbonyl
      complex. Thus, replacement of the negatively charged E250 with an uncharged,
      polar serine residue substantially hampered assembly of CYP2B4 (delta2-27);
      introduction of an alpha-helix-disrupting proline completely blocked the
      formation of holoenzyme. These phenomena suggested that the negative charge of
      E250, residing in the putative G helix, underwent pairing with some positively
      charged group, possibly H285 located in the I helix. Deletion of the negative
      charge obviously perturbed the active-site geometry such as to affect both the
      incorporation and/or retention of the heme ligand and the spectral binding of
      substrates such as hexobarbital.

PMID- 9623770
TI  - HPLC and light scattering detection allow the determination of phospholipids in
      biological samples and the assay of phospholipase A2.
AB  - Some applications to biological samples of a method for the separation and the
      quantitative analysis of phospholipids by high performance liquid chromatography
      (HPLC) and light scattering mass detection are described. Results obtained in the
      determination of phospholipid classes from rat tissues such as liver, heart and
      kidney have been compared with data from the literature. The method has been
      applied to the evaluation of phospholipids in human low-density lipoproteins
      (LDL), about which little is known. The procedure is also suitable for a rapid
      and reliable assay of the water-soluble phospholipase A2 activity; the
      relationship between the aggregation state of substrate phospholipids (mixed
      micelles, multilamellar and unilamellar vesicles) and the enzyme activity has
      been studied.

PMID- 9623771
TI  - Chemical modification of dextransucrase from Leuconostoc mesenteroides NRRL B
      512F by pyridoxal 5'-phosphate: evidence for the presence of an essential lysine
      residue at the active site.
AB  - The treatment of Leuconostoc mesenteroides NRRL B-512F dextransucrase with lysine
      specific reagent, pyridoxal 5'-phosphate (PLP) at pH 5.2 and 30 degrees C
      resulted in the loss of enzyme activity. The inactivation by PLP could be
      reversed completely by dilution or dialysis. Sucrose as well as acceptor
      substrates, glucose and dextran protected the enzyme against inactivation by PLP.
      A statistical, kinetic analysis of the inactivation by PLP showed that one lysine
      residue is essential for the enzyme activity. All these results showed that one
      lysine residue present at the active is essential for the activity of
      dextransucrase.

PMID- 9623772
TI  - In vitro transcription of c-jun gene using fractionated nuclear extract from
      regenerating rat liver.
AB  - Regenerating rat liver serves as a source of proliferating cells, such a system
      can be used to study the regulation of genes involved in proliferation. We have
      established an in vitro transcription capable of supporting accurate
      transcription of cloned c-jun gene using fractionated nuclear extract prepared
      from partially hepatectomized rat liver. EcoR I linearized plasmid -132/+170 jun
      CAT containing c-jun gene promoter region (-132 to +170 nucleotides) was
      transcribed in an in vitro run-off transcription assay and a transcript of
      expected size i.e. 370 nucleotides was obtained. The intensity of the transcript
      was dependent on the concentration of fractionated nuclear extract as well as
      template. The transcription was alpha-amanitin sensitive indicating that it is
      directed by RNA polymerase II.

PMID- 9623774
TI  - Molecular cloning and expression of mouse ceramide glucosyltransferase.
AB  - Ceramide glucosyltransferase (EC 2.4.1.80) catalyzes the first glycosylation step
      of glycosphingolipid (GSL) synthesis, the transfer of glucose from UDP-Glucose to
      hydrophobic ceramide and generate glucosylceramide (GlcCer). We have cloned mouse
      ceramide glucosyltransferase cDNA from a brain cDNA library by PCR based homology
      cloning. The nucleotide sequence determination revealed that mouse ceramide
      glucosyltransferase cDNA encodes 394 amino acids with a calculated molecular mass
      of 45 kDa. The amino acid sequence of mouse ceramide glucosyltransferase showed
      98% identity with the human sequence. Homology searches against currently
      available databases identified three homologous proteins in Caenorhabditis
      elegans and one homologous protein in Cyanobacteria. Highly conserved sequences
      of ceramide glucosyltransferases and the homologs among a wide variety of
      organisms suggest biological significance of the lipid glucosylation system.

PMID- 9623773
TI  - Effects of short- and long-term exposure to linoleic acid hydroperoxide on
      cytosolic calcium ion level of human aortic intimal smooth muscle cells in vitro.
AB  - When cultured intimal smooth muscle cells from human aorta were exposed for a
      short period of time (25 sec) to linoleic acid hydroperoxide (100 nmol/ml),
      influx of calcium ions into the cytosol of these cells was provoked, and a
      temporal increase in cytosolic calcium ion level was observed. Two calcium
      channel blockers inhibited this influx. Long-term exposure (4 min) of these cells
      to the hydroperoxide also provoked the influx of calcium ions, which resulted in
      a longer time of the calcium ion increase. In the latter case, however, the
      calcium channel blocker inhibited the initial influx, but then the influx started
      and continued even in the presence of the blocker. Such difference in exposure
      time-dependent effects should be taken into account in considering pathological
      roles of lipid hydroperoxides.

PMID- 9623775
TI  - Signal transduction by the peptide which mimics the activity of thrombopoietin.
AB  - Thrombopoietin (TPO) plays a central role in megakaryopoiesis and platelet
      production. It is a ligand for c-mpl, which is a member of the hematopoietic
      receptor superfamily. We have recently identified several human c-mpl binding
      peptides which are distinct from TPO, from phage random peptide libraries. PK1M
      is one of these peptides and is an agonist of c-mpl which is TPO receptor. We
      show here that PK1M induces the tyrosine phosphorylation of the Janus kinase 2
      (JAK2) and the activation of the signal transducer and activation of
      transcription 5 (STAT5) in TPO-dependent cells like TPO.

PMID- 9623776
TI  - Branched-chain alpha-keto acid dehydrogenase kinase content in rat skeletal
      muscle is decreased by endurance training.
AB  - The activity state of branched-chain alpha-keto acid dehydrogenase complex in
      skeletal muscle was elevated by running exercise in trained and untrained rats,
      but level of this elevation was significantly greater in the former than in the
      latter. To elucidate the mechanism of the training effect on the exercise-induced
      activation of the complex, a protein amount of branched-chain alpha-keto acid
      dehydrogenase kinase, which is responsible for inactivation of the complex by
      phosphorylation, in the muscle was measured by the Western blot analysis.
      Endurance training decreased the content of the kinase protein in the muscle by
      approximately 30%, suggesting that this decrease is involved in the mechanisms
      for greater activation of the complex by exercise in trained rats.

PMID- 9623777
TI  - A method for uni-directional reconstitution of human erythrocyte glucose
      transporter.
AB  - The glucose transporter of human erythrocytes (Glut1) was reconstituted into
      soybean phospholipid liposomes by a method of direct incorporation using the
      nonionic detergent n-octyl beta-D-glucopyranoside. The reconstituted
      proteoliposomes were proved to be intact and low ionic permeability. Freeze
      fracture electron microscopy study showed that the diameter of the
      proteoliposomes was about 150 +/- 50 nm and the protein was randomly distributed.
      The kinetic parameters of the reconstituted transporter were: Km =16.23 mmol/L,
      Vmax = 34.48 nmol/sec x mg protein. Furthermore, about 90% of the glucose
      transporter in the reconstituted proteoliposomes were orientated inside-out.
      Until now it is a more efficient method for uni-directional reconstitution of
      Glut1 with good reproducibility and higher transport activity.

PMID- 9623778
TI  - Differential oligomerization of membrane-bound CD38/ADP-ribosyl cyclase in
      porcine heart microsomes.
AB  - A protein fraction displaying ADP-ribosyl cyclase activity was purified from
      porcine heart microsomes which appeared as a major band of 45 kDa on Coomassie
      blue stained SDS-PAGE gel under reducing condition. Protein immunoblot analysis
      with antiserum to recombinant rat CD38 showed a series of bands (45-285 kDa)
      under nonreducing condition, while only the 45 kDa monomer under reducing
      condition. The high molecular weight oligomers of CD38 were found to be stable
      even upon treatment with various concentrations of SDS in the sample buffer and
      also upon incubation at lower temperature. These oligomers of CD38 also displayed
      higher ADP-ribosyl cyclase activity than that of the monomer.

PMID- 9623779
TI  - Effect on colon cancer cells of human interferon-beta gene entrapped in cationic
      multilamellar liposomes.
AB  - When cultured cells of human colon cancer cell line SW480 were transfected with
      human interferon-beta (hIFN-beta) gene by means of cationic multilamellar
      liposomes, the endogenously produced hIFN-beta exhibited a remarkable anti
      proliferative effect on the cells, which was more effective than that of
      exogenously added hIFN-beta. This effect lasted for several days, and was blocked
      completely by the addition of sufficient amounts of anti-hIFN-beta antibody. From
      experiments using a transwell plate and an infusion pump, we found that
      endogenously produced hIFN-beta acted effectively on the cells around the
      transfectants and that the growth-inhibitory effect was totally retained upon
      continuous dilution of the medium. These data indicate that hIFN-beta expressed
      endogenously by transfer of its gene acted on these cancer cells mainly in a
      paracrine manner. Although the transfection with hIFN-gamma gene also revealed a
      definite growth-inhibitory effect on the same tumor cells, the extent was less
      than that of hIFN-beta gene.

PMID- 9623780
TI  - Molecular cloning and regulation of a novel guinea pig cytochrome P450 (CYP3A20)
      which differs from guinea pig CYP3A14 in only two amino acid residues.
AB  - A full length cDNA clone of cytochrome P450, encoding 503 amino acid residues,
      was isolated from a male guinea pig liver cDNA library. The sequence was highly
      homologous to other members in the CYP3A subfamily and was designated CYP3A20.
      CYP3A20 and CYP3A14, another guinea pig CYP3A, shared 99.4% nucleotide and 99.6%
      deduced amino acid sequence homology. There were only two amino acid differences
      between CYP3A20 and CYP3A14. No significant induction of CYP3A20 mRNA in the
      livers from male guinea pigs treated with dexamethasone was observed by S1
      mapping analysis although CYP3A14 mRNA was induced. The expression of CYP3A20
      mRNA in the livers did not change between 5 and 10 weeks after birth while that
      of CYP3A14 mRNA in livers significantly increased at 10 weeks. This is the first
      report that the two highly resembling forms of cytochrome P450 display
      differently regulated expression from each other.

PMID- 9623781
TI  - Effect of vitamin E on antioxidant enzymes and nitric oxide in ischemia
      reperfused kidney injury.
AB  - The effects of Vitamin E administration on antioxidant enzyme activities and
      nitrite-nitrate levels of the reperfused rat kidney tissues were investigated by
      performing a 60 min ischemia followed by 24 and 72 hours of reperfusion. Vitamin
      E administration or the placebo (SF) was applied as 100 mg/kg BW. As expected,
      catalase (CAT) (p<0.05) and superoxide dismutase (SOD) (p<0.05) activities of
      ischemia/reperfused (I/R) kidney tissue were lower and malondialdehyde (MDA)
      levels were higher than control kidneys in both SF and vitamin E treated groups
      following 24 h reperfusion. During reperfusion of long term (72 h), vitamin E
      triggered a decrease in the MDA levels in the ischemic tissue, while it did not
      provoke a significant effect on SOD and catalase activities. Total nitrite levels
      of ischemic tissues in both of the groups were higher than matched control
      kidneys and this elevation was more clear in the vitamin E treated group. Our
      results showed that vitamin E has a protective effect on I/R injury, by a direct
      chain breaking effect on lipid peroxidation (LPO) and hence preventing the nitric
      oxide (NO) reservoir of ischemic tissue. Alfa-tocopherol may be a promising agent
      for the prevention of tissue injury caused by free oxygen radicals.

PMID- 9623782
TI  - Characterisation of L-[3H]glutamate binding to fresh and frozen crude plasma
      membranes isolated from cerebral cortex of adult rats.
AB  - Specific [3H]glutamate binding to fresh crude plasma membranes (CPMs) was
      compared with binding to frozen CPMs and the optimal conditions for the binding
      to frozen CPMs isolated from cerebral cortex of adult rats were determined.
      Freezing reduced [3H]glutamate binding (3.5-fold), and pre-incubation of
      previously frozen membranes followed by three washes increased binding (4.5-fold)
      when compared to fresh samples. CPMs washed once, pre-incubated at 37 degrees C
      and washed 3 times was adopted as the most adequate condition for the binding
      assay of frozen membranes. In a Cl(-)-containing medium, [3H]glutamate binding
      (Bmax=97.9 pmol/mg, Kd=349.68 nM) to this frozen CPM preparation was
      significantly displaced by excess quisqualic acid (QA) (65%), L-2-amino-4
      phosphonobutyric acid (L-AP4) (35%), trans-1-aminocyclopentane-1,3-dicarboxylate
      (1S,3R-ACPD) (25%) and alfa-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)
      (25%). In a Cl(-)-free medium, binding (Bmax=44.14 pmol/mg, 311 nM) was
      significantly displaced by QA (45%), L-AP4 (25%), ACPD (25%), AMPA (25%), kainic
      acid (20%) and N-methyl-D-aspartate (15%).

PMID- 9623784
TI  - Disturbed small intestinal motility in the late rat pregnancy.
AB  - We investigated whether various periods of pregnancy might disturb rat
      gastrointestinal motility. When the proestrus of female rats occurred, they were
      housed with male rats. Motility studies were conducted on day 7 (first period),
      day 14 (second) and day 21 (third) of pregnancy, respectively. After the
      orogastric feeding of radiochromium marker, rats were sacrificed 15 min later.
      Gastric emptyings of pregnant rats measured at various periods did not differ
      from the nonpregnant diestrus controls. The geometric center represented
      intestinal transits in the first, second and third periods of pregnancy and
      controls were (mean+/-SEM) 4.54+/-0.25, 4.47+/-0.17, 3.61+/-0.27 and 4.98+/-0.13,
      respectively (p < 0.01) while their plasma progesterone levels were 15.6+/-2.6,
      18+/-1.4, 7.1+/-0.5 and 8.6+/-0.4 ng/ml, respectively (p< 0.01). This shows that
      late pregnancy inhibits small intestinal transit, whereas gastric emptying
      remains unchanged. Altered progesterone during pregnancy is not a main mediator
      to disturb intestinal transit.

PMID- 9623783
TI  - Effect of age on pregnancy outcome without assisted reproductive technology in
      women with elevated early follicular phase serum follicle-stimulating hormone
      levels.
AB  - There are data suggesting that patients with elevated early follicular phase
      serum follicle-stimulating hormone (FSH) levels have a poor fertility outcome.
      This has been attributed to a high rate of aneuploidy in the oocytes. It is not
      clear whether the spindle defects leading to nondisjunction are related to the
      high FSH levels or the age of the oocyte. The study presented herein
      retrospectively evaluated 6-month pregnancy rates in women with elevated early
      follicular phase serum FSH levels according to age. Only cases without in vitro
      fertilization were used, since the elevated FSH levels were deemed likely to
      interfere with multiple egg recruitment needed for assisted reproductive
      technology. The 6-month clinical and ongoing pregnancy rates were significantly
      higher in the women <40 years of age (46.1 and 34.6%, respectively) than in those
      aged 40 or older (10.5 and 5.3%). These data suggest that women with elevated
      follicular-phase serum FSH levels have a better fertility prognosis when they are
      younger.

PMID- 9623785
TI  - Measurement of intrauterine human decidua-associated protein 200 and diagnosis of
      ectopic pregnancy.
AB  - The aim of the current study was to examine whether the measurement of
      intrauterine human decidua-associated protein (hDP) 200 might be of clinical
      value in the diagnosis of ectopic pregnancy versus early missed abortion. Uterine
      fluid levels of hDP 200 were measured in two groups of patients: 20 women with
      ectopic pregnancy, diagnosed by laparoscopy, and 20 women diagnosed (after
      curettage) as having a missed abortion. No significant difference in hDP 200
      levels was observed comparing patients with ectopic pregnancy (mean 114.0+/-58.2
      mU/ml) and patients with early missed abortion (mean 222.0+/-116.0 mU/ml),
      although a trend towards lower levels of uterine fluid hDP 200 was noted in the
      group of patients presenting with tubal pregnancy. Thus, according to our data,
      intrauterine hDP 200 is not sufficiently discriminative to be of clinical value
      in the diagnosis of ectopic pregnancy.

PMID- 9623786
TI  - Comparison of the differential distribution of leukocytes in preeclampsia versus
      uncomplicated pregnancy.
AB  - OBJECTIVE: To describe leukocyte count and differential distribution in
      preeclampsia and uncomplicated pregnancy. STUDY DESIGN: Blood samples were
      obtained from 46 consecutive preeclamptic patients and 46 controls with
      uncomplicated pregnancy. Thirty met the criteria for mild preeclampsia and 16 for
      severe. The blood was tested within 1 h of venepuncture. An aliquot of the blood
      was tested in the Cell-Dyn 2000 for complete blood cell count. MAIN RESULTS: The
      absolute neutrophil count was significantly elevated in preeclamptic patients as
      compared with that of controls with uncomplicated pregnancy (9,410.1+/-3,066.9
      vs. 7,498.6+/-2,354.0 x 10(6)/l, p < 0.05). In neutrophils, the elevation was
      more prominent in severe preeclamptic patients as compared with mild preeclamptic
      patients (10,658.8+/-3520.4 vs. 8,694.4+/-2,561.9 x 10(6)/l, p < 0.05). The
      absolute lymphocyte and eosinophil counts declined in patients with preeclampsia
      as compared with uncomplicated pregnancy, whereas monocyte and basophil counts
      did not differ. CONCLUSION: Our results suggest that preeclampsia is associated
      with an increase in the absolute neutrophil count.

PMID- 9623787
TI  - Perinatal outcome of oligohydramnios without associated premature rupture of
      membranes and fetal anomalies.
AB  - To investigate the perinatal outcome of patients with oligohydramnios (amniotic
      fluid index < or = 5 cm), but without premature rupture of membranes and fetal
      congenital anomalies, data from 245 singleton pregnancies were analyzed and
      compared to those with normal amniotic fluid volumes (5 < amniotic fluid index <
      24 cm, n=27,261). Significantly higher incidences of primiparity, pregnancy
      induced hypertension, premature separation of placenta, past history of
      intrauterine fetal death, past history of preterm delivery, postterm pregnancy,
      and advanced maternal age were noted to be associated with the occurrence of
      oligohydramnios. Pregnancies complicated by a markedly diminished amniotic fluid
      volume assessed antenatally by ultrasound were significantly more frequently
      associated with adverse perinatal outcomes such as preterm delivery, low or very
      low birth weight, low Apgar scores, intrauterine fetal death, small-for
      gestational-age newborns, meconium staining, cesarean delivery, neonatal
      intensive care, and neonatal death.

PMID- 9623788
TI  - Urinary PGE2 and PGF2alpha levels and renal functions in preeclampsia.
AB  - The role of prostaglandin E2 (PGE2) and prostaglandin F2alpha (PGF2alpha) in the
      pathogenesis of hypertension and altered renal functions, which are the main
      symptoms of preeclampsia, has gained importance. Serum and urine samples of 59
      women (24 preeclamptic pregnant (PEP), 20 normotensive pregnant (NTP) and 15
      nonpregnant) were investigated by means of prostaglandin levels and urea,
      creatinine and creatinine clearance values. PEP patients, when compared with NTP
      patients, show a significant decrease in PGE2 and PGF2alpha levels (p < 0.01 and
      p < 0.05, respectively) accompanied by changes in some parameters of renal
      function such as serum urea, creatinine and creatinine clearance. Although
      disorders in prostaglandin levels may be responsible for some renal pathologic
      changes, renal functional and morphologic alterations may also result in abnormal
      prostaglandin activity.

PMID- 9623789
TI  - Progesterone increases cAMP release and accumulation in isolated term human
      myometrium.
AB  - OBJECTIVE: To study the relationship between the action of progesterone on term
      human myometrial contractile activity and cAMP alterations. STUDY DESIGN:
      Myometrial tissues were obtained from 13 term pregnant women who underwent
      elective cesarean section. The contractile activity of muscle strips was recorded
      isometrically, and the level of cAMP in both superfusion media and experimental
      biopsies was measured by radioimmunoassay. RESULTS: An increased cAMP release
      into the superfusion media and an increased accumulation of cAMP in myometrium
      were observed after the addition of progesterone (3, 15 and 150 microM).
      Simultaneously, the frequency and tonus of contractions were increased, while the
      amplitude and activity area of contractions were decreased. CONCLUSIONS: The data
      indicate that an increase in cAMP concentration plays a role in the action of
      progesterone on the regulation of term human myometrial contractile activity.

PMID- 9623790
TI  - Plasma melatonin profile and hormonal interactions in the menstrual cycles of
      anovulatory infertile women treated with gonadotropins.
AB  - The patterns of plasma melatonin, gonadotropins, sex steroids and prolactin were
      studied in anovulatory infertile females undergoing ovulation induction with
      hMG/hCG. Melatonin levels were found to fluctuate during the menstrual cycle of
      these subjects with a nadir at mid-cycle and peak occurring at the early
      follicular/late luteal phases of the cycle (p < 0.05). Melatonin correlated
      negatively with estradiol during the follicular phase (r=-0.5180, p < 0.05) and
      positively with LH (5 + 0.6321, p < 0.05) in the luteal phase, respectively.
      Correlational analyses by partial and multiple correlations suggest that the
      effects of estradiol and LH on melatonin in the follicular phase are
      interdependent whereas the effect of LH on melatonin in the luteal phase is
      independent of the effects of other hormones. The results suggest that hormonal
      interactions and phases of the cycle are important variables contributing to the
      fluctuations in melatonin levels during the menstrual cycle.

PMID- 9623791
TI  - Localization of matrix metalloproteinase-2 in uterine endometrium and ectopic
      implants.
AB  - We performed an immunohistochemical study on paraffin-embedded tissues to
      evaluate the invasion pattern of endometriotic implants by determination of
      matrix metalloproteinase (gelatinase A) expression. Endometriotic tissues (n=32)
      and uterine endometria (n=18) of patients with endometriosis and uterine
      endometria of normal-menstruating women without endometriosis (n=11) were
      examined. Endometriotic tissues showed statistically significantly stronger
      staining compared with uterine endometria. However, we did not find differences
      in staining between uterine endometrium of women with endometriosis and normal
      controls. Compared to uterine endometrium, ectopic endometrium has a
      significantly higher capacity to produce the latent forms (72 kD) of gelatinase
      A. This leads to the conclusion that endometriotic implants express the protease
      enabling the invasion of surrounding tissue.

PMID- 9623792
TI  - Compared randomized roles and pain factor by Vabra and Wallach Endocell in
      endometrial evaluation.
AB  - This randomized study was carried out to compare pain factors of Vabra and
      Endocell by an ordered classification of one to ten to evaluate the respective
      pathological yield and to establish the clinical acceptability. Patients had
      endometrial evaluation either for abnormal bleeding, abnormal endometrial line as
      demonstrated by echography or abnormal endometrial cells in the Pap smear. Age,
      gravidity, parity and hysterometry were similar in both groups, with abnormal
      bleeding being the most frequent indication (250/370 patients, 67.5%). Both
      techniques yielded equal results for insufficient tissue retrieval at 46/184
      (25.0%) for Vabra and at 50/183 (27.3%) for Endocell. The pain score differed
      significantly in favor of Wallach Endocell at 4.36+/-2.38 versus Vabra at 5.65+/
      2.41 (p=0.001). Vabra and Endocell give similar pathological results; however,
      Endocell is significantly less painful and easier to manipulate and carry because
      of its weight (1.69 g vs. 37.80 g).

PMID- 9623793
TI  - Laparoscopic suturing technique for total abdominal hysterectomy.
AB  - The objective of this report is to present the laparoscopic technique for total
      abdominal hysterectomy executed with no transvaginal approach, and by suturing
      and tying an extracorporeal sliding and an intracorporeal two-flat square knot.
      The hysterectomy methodology itself was adapted from classic abdominal
      hysterectomy and completed via laparoscopy with necessary modifications to meet
      laparoscopic technology standards. Following uterine extirpation, prophylactic,
      retroperitoneal posterior culdoplasty (the retroperitoneal layer of the
      uterosacral ligaments, rectal fascia, and paravaginal fascia were incorporated
      into the reconstructive process), and vaginal vault re-suspension were executed
      posteriorly, to the deep layer of the uterosacral ligaments, laterally, to the
      cardinal ligaments, and anteriorly, to the vesicocervical fascia. Laparoscopic
      total abdominal hysterectomy with posterior culdoplasty and vaginal vault
      suspension by suturing method appeared to be a safe and effective operation.

PMID- 9623794
TI  - Combined ultrasonographically guided drainage and laparoscopic excision of large
      endometriomas: a pilot study.
AB  - We report a prospective pilot study which evaluated the feasibility of combined
      ultrasonographically guided drainage and laparoscopic excision after pre
      operative administration of a gonadotrophin-releasing hormone analogue for 3
      months in the management of ovarian endometriotic cysts >5 cm. Ten patients with
      an ultrasonographic diagnosis of large unilateral or bilateral ovarian
      endometriotic cysts received an intramuscular injection of leuprorelinum acetate
      3.75 every 4 weeks for 12 weeks. After 4 weeks of medical treatment, the
      endometrioma was carefully drained transabdominally under ultrasonographic
      control. Within 8 weeks since the last injection, the patients were submitted to
      a second ultrasonography, and laparoscopy-guided stripping of the endometrioma
      was performed. A videotape review was undertaken to evaluate duration and
      complexity of the different phases of surgery. Stripping of endometriomas with
      preservation of residual ovarian parenchymas was obtained in all cases;
      adhesiolysis was complete in 6 cases. There were neither intra-operative
      complications nor conversions in laparotomy. In conclusion, gonadotrophin
      releasing hormone analogue and cyst drainage seem to permit an easy laparoscopic
      approach of large endometriomas; the findings of our pilot phase seem to justify
      a randomized trial to better define the effectiveness of this approach with
      respect to standard procedures.

PMID- 9623795
TI  - Increased serum concentrations of soluble vascular cell adhesion molecule-1 in
      uterine cervical cancer.
AB  - The purpose of this investigation was to determine the serum concentration of
      soluble vascular cell adhesion molecule-1 (sVCAM-1) in women with squamous cell
      carcinoma of the cervix. Serum samples were obtained from 38 Japanese women with
      squamous cell carcinoma of the cervix before initial treatment (12 in stage 0, 7
      in stage I, 5 in stage II, 9 in stage III and 5 in stage IV), 7 patients with a
      recurrence of this cancer, and 18 healthy female volunteers. Serum sVCAM-1 was
      measured with a sandwich enzyme-linked immunosorbent assay. Serum concentrations
      (means+/-SD) of sVCAM-1 in the healthy volunteers, the patients with cervical
      cancer in stages 0-IV and in the patients with recurrent tumors were 597.2+/
      151.4, 690.1+/-214.2, 1,234.8+/-466.1, 1,159.8+/-825.8, 1,529.6+/-662.0,
      1,053.0+/-228.8, and 1,134.8+/-211.3 ng/ml, respectively. Values for patients
      with stages I-IV or recurrent cervical cancer were significantly increased
      compared to those for healthy volunteers (p < 0.05). Results suggest that sVCAM-1
      is shed from endothelial cells in the cancerous tissue.

PMID- 9623796
TI  - MTAP gene deletion in endometrial cancer.
AB  - A gene (MTAP) that encodes the enzyme 5'-deoxy-5'-methylthioadenosine (MTA)
      phosphorylase has been identified on chromosome 9p21 and cloned. The substrate of
      this enzyme, MTA, inhibits aminopropyltransferases that synthesize polyamines
      from putrescine and decarboxylated S-adenosylmethionine. This enzyme normally
      cleaves MTA to adenine and 5'-methylthioribose-1-phosphate, which are recycled to
      adenine nucleotides and methionine, respectively. Cancers with deletions of the
      MTAP gene may be especially susceptible to chemotherapeutic regimes which
      interfere with purine or methionine utilization. The purpose of this study was to
      determine deletion of the MTAP gene in endometrial cancer using a polymerase
      chain reaction-based method. Therefore, 50 endometrial adenocarcinomas were
      studied. Partial or total deletions of the MTAP gene were detected in 7 (14%) of
      these cancers. There were no significant relationships between gene deletion and
      patient age, pathological grade or clinical stage (p > 0.05). The findings
      indicate that deletion of the MTAP gene does occur in a subgroup of endometrial
      cancer. The present work may be extended to the development of molecular
      diagnosis of MTAP gene deletion in other cancers and assist in selecting
      appropriate chemotherapy.

PMID- 9623797
TI  - Antenatal molecular diagnosis of X-linked ichthyosis by maternal serum screening
      for Down's syndrome.
AB  - A case of X-linked ichthyosis diagnosed antenatally by molecular analysis of
      fetal DNA is described. The diagnosis was made at 16 weeks gestation, following
      the finding of a maternal serum unconjugated estriol level lower than 0.1 MoM
      when performing a triple test. Fetal DNA was obtained from cultured amniocytes;
      two specific regions were amplified by polymerase chain reaction at 5' and 3'
      ends of the steroid sulfatase (STS) gene on Xp22.3 region. Analysis showed
      complete deletion of the STS gene on the distal tip of the X-chromosome short
      arm.

PMID- 9623798
TI  - Dysuria due to bladder distortion after repeat cesarean section.
AB  - Abnormalities of the lower urinary tract resulting from cesarean section are
      rare. We present a patient who developed urinary frequency, nocturia and acute
      pains in the late phase of micturition which we think was due to bladder
      distortion after repeat cesarean section. She was diagnosed cystographically and
      treated successfully by bladder flap release.

PMID- 9623799
TI  - Cytochrome oxidase: structure and mechanism. Foreword.

PMID- 9623800
TI  - Crystal structure of bovine heart cytochrome c oxidase at 2.8 A resolution.
AB  - Thirteen different polypeptide subunits, each in one copy, five phosphatidyl
      ethanolamines and three phosphatidyl glycerols, two hemes A, three Cu ions, one
      Mg ion, and one Zn ion are detectable in the crystal structure of bovine heart
      cytochrome c oxidase in the fully oxidized form at 2.8 A resolution. A propionate
      of hems a, a peptide unit (-CO-NH-), and an imidazole bound to CuA are hydrogen
      bonded sequentially, giving a facile electron transfer path from CUA to heme a.
      The O2 binding and reduction site, heme a3, is 4.7 A apart from CuB. Two possible
      proton transfer paths from the matrix side to the cytosolic side are located in
      subunit I, including hydrogen bonds and internal cavities likely to contain
      randomly oriented water molecules. Neither path includes the O2 reduction site.
      The O2 reduction site has a proton transfer path from the matrix side possibly
      for protons for producing water. The coordination geometry of CuB and the
      location of Tyr244 in subunit I at the end of the scalar proton path suggests a
      hydroperoxo species as the two electron reduced intermediate in the O2 reduction
      process.

PMID- 9623801
TI  - From NO to OO: nitric oxide and dioxygen in bacterial respiration.
AB  - Nitric oxide reductase (NOR) is a key enzyme in denitrification, reforming the N
      N bond (making N2O from two NO molecules) in the nitrogen cycle. It is a
      cytochrome bc complex which has apparently only two subunits, NorB and NorC. It
      contains two low-spin cytochromes (c and b), and a high-spin cytochrome b which
      forms a binuclear center with a non-heme iron. NorC contains the c-type heme and
      NorB can be predicted to bind the other metal centers. NorB is homologous to the
      major subunit of the heme/copper cytochrome oxidases, and NOR thus belongs to the
      superfamily, although it has an Fe/Fe active site rather than an Fe/Cu binuclear
      center and a different catalytic activity. Current evidence suggests that NOR is
      not a proton pump, and that the protons consumed in NO reduction are not taken
      from the cytoplasmic side of the membrane. Therefore, the comparison between
      structural and functional properties of NOR and cytochrome c- and quinol
      oxidizing enzymes which function as proton pumps may help us to understand the
      mechanism of the latter. This review is a brief summary of the current knowledge
      on molecular biology, structure, and bioenergetics of NOR as a member of the
      oxidase superfamily.

PMID- 9623802
TI  - Regulation of energy transduction and electron transfer in cytochrome c oxidase
      by adenine nucleotides.
AB  - Cytochrome c oxidase from bovine heart contains seven high-affinity binding sites
      for ATP or ADP and three additional only for ADP. One binding site for ATP or
      ADP, located at the matrix-oriented domain of the heart-type subunit VIaH,
      increases the H+/e- stoichiometry of the enzyme from heart or skeletal muscle
      from 0.5 to 1.0 when bound ATP is exchanged by ADP. Two further binding sites for
      ATP or ADP, located at the cytosolic and the matrix domain of subunit IV,
      increases the K(M) for cytochrome c and inhibit the respiratory activity at high
      ATP/ADP ratios, respectively. We propose that thermogenesis in mammals is related
      to subunit VIaL of cytochrome c oxidase with a H+/e- stoichiometry of 0.5
      compared to 1.0 in the enzyme from bacteria or ectotherm animals. This hypothesis
      is supported by the lack of subunit VIa isoforms in cytochrome c oxidase from
      fish.

PMID- 9623803
TI  - Pathways for electron tunneling in cytochrome c oxidase.
AB  - Warburg showed in 1929 that the photochemical action spectrum for CO dissociation
      from cytochrome c oxidase is that of a heme protein. Keilin had shown that
      cytochrome a does not react with oxygen, so he did not accept Warburg's view
      until 1939, when he discovered cytochrome a3. The dinuclear cytochrome a3-CuB
      unit was found by EPR in 1967, whereas the dinuclear nature of the CuA site was
      not universally accepted until oxidase crystal structures were published in 1995.
      There are negative redox interactions between cytochrome a and the other redox
      sites in the oxidase, so that the reduction potential of a particular site
      depends on the redox states of the other sites. Calculated electron-tunneling
      pathways for internal electron transfer in the oxidase indicate that the coupling
      limited rates are 9 x 10(5) (CuA-->a) and 7 x 10(6) s(-1) (a-->a3); these
      calculations are in reasonable agreement with experimental rates, after
      corrections are made for driving force and reorganization energy. The best CuA-a
      pathway starts from the ligand His204 and not from the bridging sulfur of Cys196,
      and an efficient a-a3 path involves the heme ligands His378 and His376 as well as
      the intervening Phe377 residue. All direct paths from CuA to a3 are poor,
      indicating that direct CuA-->a3 electron transfer is much slower than the CuA-->a
      reaction. The pathways model suggests a means for gating the electron flow in
      redox-linked proton pumps.

PMID- 9623804
TI  - Investigating the mechanism of electron transfer to the binuclear center in Cu
      heme oxidases.
AB  - Novel experimental evidence is presented further supporting the hypothesis that,
      starting with resting oxidized cytochrome c oxidase, the internal electron
      transfer to the oxygen binding site is kinetically controlled. The reduction of
      the enzyme was followed spectroscopically and in the presence of NO or CO, used
      as trapping ligands for reduced cytochrome a3; ruthenium hexamine was used as a
      spectroscopically silent electron donor. Consistent with the high combination
      rate constant for reduced cytochrome a3, NO proved to be a very efficient
      trapping ligand, while CO did not. The results are discussed in view of two
      alternative (thermodynamic and kinetic) hypotheses of control of electron
      transfer to the binuclear (cyt.a3-CuB) center. Fulfilling the prediction of the
      kinetic control hypothesis: i) the reduction of cytochrome a3 and ligation are
      synchronous and proceed at the intrinsic rate of cytochrome a3 reduction, ii) the
      measured rate of formation of the nitrosyl derivative is independent of the
      concentration of both the reductant and NO.

PMID- 9623805
TI  - Determination and novel features of the absolute absorption spectra of the heme a
      moieties in cytochrome c oxidase.
AB  - The absolute absorption spectra of the two heme a moieties in cytochrome c
      oxidase were determined in the Soret region where spectral contributions from
      copper ions are negligible. This determination employs a set of absorption
      spectra of the enzyme recorded during anaerobic reduction with sodium dithionite,
      and does not require any other spectral data. The unique feature of the component
      spectra revealed in the present study suggests the existence of a specific
      interaction of heme a with the immediate environment as its origin. The
      usefulness of the absolute spectra in quantitative analysis of the spectral data
      is presented.

PMID- 9623806
TI  - The dinuclear center of cytochrome bo3 from Escherichia coli.
AB  - For the study of the dinuclear center of heme-copper oxidases cytochrome bo3 from
      Escherichia coli offers several advantages over the extensively characterized
      bovine cytochrome c oxidase. The availability of strains with enhanced levels of
      expression allows purification of the significant amounts of enzyme required for
      detailed spectroscopic studies. Cytochrome bo3 is readily prepared as the fast
      form, with a homogeneous dinuclear center which gives rise to characteristic
      broad EPR signals not seen in CcO. The absence of CuA and the incorporation of
      protohemes allows for a detailed interpretation of the MCD spectra arising from
      the dinuclear center heme o3. Careful analysis allows us to distinguish between
      small molecules that bind to heme o3, those which are ligands of CuB, and those
      which react to yield higher oxidation states of heme o3. Here we review results
      from our studies of the reactions of fast cytochrome bo3 with formate, fluoride,
      chloride, azide, cyanide, NO, and H2O2.

PMID- 9623808
TI  - Time-resolved resonance Raman investigation of oxygen reduction mechanism of
      bovine cytochrome c oxidase.
AB  - Six oxygen-associated resonance Raman bands were identified for intermediates in
      the reaction of bovine cytochrome c oxidase with O2 at room temperature. The
      primary intermediate, corresponding to Compound A of cryogenic measurements, is
      an O2 adduct of heme a3 and its isotope frequency shifts for 16O18O have
      established that the binding is of an end-on type. This is followed by two
      oxoheme intermediates, and the final intermediate appearing around 3 ms is the Fe
      OH heme. The reaction rate between the two oxoheme intermediates is significantly
      slower in D2O than in H2O, suggesting that the electron transfer is regulated by
      proton translocations at this step. It is noted that the reaction intermediates
      of oxidized enzyme with hydrogen peroxide yield the same three sets of oxygen
      isotope-sensitive bands as those of oxoheme intermediates seen for O2 reduction
      and that the O-O bond has already been cleaved in the so-called peroxy form (or
      607 nm form).

PMID- 9623807
TI  - Reactivity of nitric oxide with cytochrome c oxidase: interactions with the
      binuclear centre and mechanism of inhibition.
AB  - Nitric oxide (NO) has recently been recognized as an important biological
      mediator that inhibits respiration at cytochrome c oxidase (CcO). This inhibition
      is reversible and shows competition with oxygen, the Ki being lower at low oxygen
      concentrations. Although the species that binds NO in turnover has been suggested
      to contain a partially reduced binuclear center, the exact mechanism of the
      inhibition is not clear. Recently, rapid (ms) redox reactions of NO with the
      binuclear center have been reported, e.g., the ejection of an electron to
      cytochrome a and the depletion of the intermediates P and F. These observations
      have been rationalized within a scheme in which NO reacts with oxidized CuB
      leading to the reduction of this metal center and formation of nitrite in a very
      fast reaction. Electron migration from CuB to other redox sites within the enzyme
      is proposed to explain the optical transitions observed. The relevance of these
      reactions to the inhibition of CcO and metabolism of NO are discussed.

PMID- 9623809
TI  - The role of electrostatic interactions for cytochrome c oxidase function.
AB  - In recent years, the enormous increase in high-resolution three-dimensional
      structures of proteins together with the development of powerful theoretical
      techniques have provided the basis for a more detailed examination of the role of
      electrostatics in determining the midpoint potentials of redox-active metal
      centers and in influencing the protonation behavior of titratable groups in
      proteins. Based on the coordinates of the Paracoccus denitrificans cytochrome c
      oxidase, we have determined the electrostatic potential in and around the
      protein, calculated the titration curves for all ionizable residues in the
      protein, and analyzed the response of the protein environment to redox changes at
      the metal centers. The results of this study provide insight into how charged
      groups can be stabilized within a low-dielectric environment and how the range of
      their electrostatic effects can be modulated by the protein. A cluster of 18
      titratable groups around the heme a3-CuB binuclear center, including a hydroxide
      ion bound to the copper, was identified that accounts for most of the proton
      uptake associated with redox changes at the binuclear site. Predicted changes in
      net protonation were in reasonable agreement with experimentally determined
      values. The relevance of these findings in the light of possible mechanisms of
      redox-coupled proton movement is discussed.

PMID- 9623810
TI  - Cytochrome c oxidase (heme aa3) from Paracoccus denitrificans: analysis of
      mutations in putative proton channels of subunit I.
AB  - One of the challenging features of energy-transducing terminal oxidases, like the
      aa3 cytochrome c oxidase of Paracoccus denitrificans, is the translocation of
      protons across the cytoplasmic membrane, which is coupled to the transfer of
      electrons to oxygen. As a prerequisite for a more advanced examination of the
      enzymatic properties, several amino acid residues, selected on the basis of
      recent three-dimensional structure determinations, were exchanged in subunit I of
      the Paracoccus enzyme by site-directed mutagenesis. The properties of the mutated
      oxidases were analyzed by different methods to elucidate whether they are
      involved in the coupled and coordinated transfer of protons via two different
      pathways either to the site of oxygen reduction or through the enzyme from the
      cytoplasm to the periplasmic side.

PMID- 9623811
TI  - Pathways of proton transfer in cytochrome c oxidase.
AB  - During the last few years our knowledge of the structure and function of heme
      copper oxidases has greatly profited from the use of site-directed mutagenesis in
      combination with biophysical techniques. This, together with the recently
      determined crystal structures of cytochrome c oxidase, has now made it possible
      to design experiments aimed at targeting specific pump mechanisms. Here, we
      summarize results from our recent kinetic studies of electron and proton-transfer
      reactions in wild-type and mutant forms of cytochrome c oxidase from Rhodobacter
      sphaeroides. These studies have made it possible to identify amino acid residues
      involved in proton transfer during specific reaction steps and provide a basis
      for discussion of mechanisms of electron and proton transfer in terminal
      oxidases. The results indicate that the pathway through K(I-362)/T(I-359), but
      not through D(I-132)/E(I-286), is used for proton transfer to a protonatable
      group interacting electrostatically with heme a3, i.e., upon reduction of the
      binuclear center. The pathway through D(I-132)/E(I-286) is used for uptake of
      pumped and substrate protons during the pumping steps during O2 reduction.

PMID- 9623812
TI  - Redox Bohr effects (cooperative coupling) and the role of heme a in the proton
      pump of cytochrome c oxidase.

PMID- 9623813
TI  - Cytochrome c oxidase as a proton-pumping peroxidase: reaction cycle and
      electrogenic mechanism.
AB  - Cytochrome oxidase (COX) is considered to integrate in a single enzyme two
      consecutive mechanistically different redox activities--oxidase and peroxidase-
      that can be catalyzed elsewhere by separate hemoproteins. From the viewpoint of
      energy transduction, the enzyme is essentially a proton pumping peroxidase with a
      built-in auxiliary eu-oxidase module that activates oxygen and prepares in situ
      H2O2, a thermodynamically efficient but potentially hazardous electron acceptor
      for the proton pumping peroxidase. The eu-oxidase and peroxidase phases of the
      catalytic cycle may be performed by different structural states of COX.
      Resolution of the proton pumping peroxidase activity of COX and identification of
      individual charge translocation steps inherent in this reaction are discussed, as
      well as the specific role of the two input proton channels in proton
      translocation.

PMID- 9623814
TI  - Protonmotive mechanism of heme-copper oxidases.
AB  - The mechanism of coupling of proton and electron transfer in oxidases is reviewed
      and related to the structural information that is now available. A "glutamate
      trap" mechanism for proton/electron coupling is described.

PMID- 9623815
TI  - On the mechanism of proton translocation by respiratory enzyme.
AB  - The protonmotive function of the respiratory heme-copper oxidases is often
      described as the sum of two separate mechanisms: a proton pump plus an incomplete
      Mitchellian redox loop. However, these two functions may be mechanistically
      intertwined so that the uptake of protons to form water during the reduction of
      O2 is a crucial part of the proton pump mechanism itself This principle can be
      deduced from thermodynamic, kinetic, mechanistic, as well as from structural
      considerations, and was first proposed in conjunction with a histidine cycle
      model of proton translocation [Morgan, J. E., Verkhovsky, M. I., and Wikstrom, M.
      (1994). J. Bioenerg. Biomembr. 26, 599-608]. However, histidine cycle models go
      much further to suggest chemical details of how this principle might be applied.

PMID- 9623816
TI  - Neurovascular free muscle transfer combined with cross-face nerve grafting for
      the treatment of facial paralysis in children.
AB  - Microneurovascular free muscle transfer is fast becoming a standardized procedure
      in the treatment of established or long-standing facial paralysis. However, there
      is no general agreement as to whether muscle transfer should be employed for
      children who still are growing. A patient's natural growth may influence or
      disturb reproduction of a smile, or a child may not be able to collaborate with
      postoperative rehabilitation sufficiently well to obtain a satisfactory result.
      One may hesitate to employ the procedure for children aged under 10 out of fear
      of its technical difficulties. To investigate the influence of age, the results
      experienced by 23 patients under the age of 15 who underwent free muscle transfer
      combined with cross-face nerve grafting were compared with those of adult
      patients. The treatment employed was a two-stage operation consisting of cross
      face nerve grafting and subsequent free muscle transfer.

PMID- 9623817
TI  - The qualification of different free muscle transplants to reconstruct mimic
      function: an experimental study in rabbits.
AB  - With the scutuloauricularis muscle, we developed a new model for experimental
      free transplantation of mimic muscles in the rabbit and studied the qualification
      of different muscles for free functional grafting into the position of the facial
      muscle, which is to be replaced. Forty adult female white New Zealand rabbits
      were distributed to four groups of 10 rabbits each. In group 1, the operative
      techniques of the new transplantation models were developed in the
      scutuloauricularis muscle, the pectoralis descendens muscle, and a comparable
      part of the rectus femoris muscle. In group 2, the scutuloauricularis muscle was
      transplanted orthotopically with microneurovascular anastomoses on the left side;
      in group 3, the pectoralis descendens muscle was transplanted into the position
      of the scutuloauricularis after its removal; and with the animals in group 4, a
      piece of the rectus femoris muscle was transplanted into the position of the
      mimic muscle after its removal. In all muscle transplants, the neurovascular
      supply was reestablished microsurgically by end-to-end anastomoses to the
      superficial temporal vessels and direct nerve coaptation to the facial nerve
      branches supplying originally the scutuloauricularis muscle. Nine months after
      transplantation, force measurements were performed in all transplanted muscles
      and the scutuloauricularis muscles of the control side. Cross-sections stained
      for ATPase after alkaline preincubation at pH 10.4 were used for computer
      assisted planimetry of the muscle fibers. The orthotopically transplanted
      scutuloauricularis muscles reached with 2.84 (+/-1.04) N for maximal tetanic
      tension on the average 87.7 (+/-32.1) percent of that of the control
      scutuloauricularis muscles, the pectoralis descendens muscles with 4.25 (+/-2.15)
      N on the average 188.7 (+/-100.7) percent of that of the controls, and the pieces
      of rectus femoris muscles 6.62 (+/-2.16) N or 185.3 (+/-45.4) percent of that of
      the controls. All three muscles were identified as fast contracting muscles
      before and after transplantation. By transplantation, the content of type II
      muscle fibers changed from 58.2 to 68.0 percent in the scutuloauricularis muscle,
      from 62.4 to 74.4 percent in the musculus pectoralis descendens, and from 92.5 to
      82.8 percent in the rectus femoris muscle. For the first time, an experimental
      model for free transplantation of mimic muscles was developed and functionally
      assessed. The most important result of this study was the fact that the double
      sized muscle grafts developed twice the force of the control scutuloauricularis
      muscles, although reinnervated by the original muscle nerve branch. This result
      underlines the usefulness of overdimensioning during clinical muscle
      transplantation. It was also shown that parts of big muscles can be grafted with
      results similar to those experienced with complete smaller muscles.

PMID- 9623818
TI  - Morphologic study of 120 skull base defects in frontoethmoidal
      encephalomeningoceles.
AB  - Frontoethmoidal encephalomeningocele is a herniation of brain and meninges
      through a congenital bone defect in the skull at the junction of the frontal and
      ethmoidal bones. From 1992 to 1996, 120 cases of frontoethmoidal
      encephalomeningocele were seen in our institutes, and the morphology of the skull
      defects was studied. The patients underwent thorough physical examinations and
      radiographic investigations including spiral three-dimensional computed
      tomography scan. Together with intraoperative findings, we found more types of
      the defects than previously reported. Our findings were categorized into the
      following types: type I, a single external opening between frontal, nasal,
      ethmoidal, and orbital bones; type IA, opening is limited between two bones of
      the area; type IB, opening is extended transversely or cephalad to involve
      adjacent structures; type II, multiple external openings in the region; type IIA,
      all of the openings are limited types; type IIB, one or more of the openings
      is/are extended type(s) that involve adjacent structures. There are 14 subtypes
      in these two types: 3 in type IA, 6 in type IB, 3 in type IIA, and 2 in type IIB.
      This classification is helpful in understanding the herniation pathway and in
      keeping informative records.

PMID- 9623819
TI  - Clinical experience with orbicularis oculi myocutaneous flaps in the temporal
      area.
AB  - There are many methods to repair facial skin defects in clinical practice. The
      desired outcome for the surgeon and the patient is the restoration of facial
      appearance and function. The temporal region is one of the ideal donor sites for
      the repair of a facial skin defect, because this area is relatively inconspicuous
      and the skin quality is similar to that of the face. In the past, the temporal
      region was always used as the donor site of the local flap for repairing the
      facial skin defect. Because the blood supply of the skin comes from the subjacent
      tissue mainly rather than from the contiguous tissue, the pedicles of the local
      flaps are short, limiting the use of this area as a donor site. From 1993 to
      1996, the anatomy of the orbicularis oculi myocutaneous flap in five cadavers was
      studied; what was learned allowed for the use of this flap to repair skin defects
      of the face in 13 patients. In this paper, the clinical experiences using the
      orbicularis oculi myocutaneous flaps to repair skin defects of the face and the
      surgical anatomy of this myocutaneous flap are discussed.

PMID- 9623820
TI  - Platysma muscle cutaneous flap for large defects of the lower lip and mental
      region.
AB  - Based on the experience acquired using the depressor anguli oris flap for lateral
      lower lip reconstruction, the authors in this paper present their own technique
      to reconstruct large deficits of the lower lateral lip, involving the commissure
      and the mental region, by means of a platysma muscle cutaneous flap with a
      triangular skin island. The flap is oriented in the mandibular cheek region. The
      skin and the platysma muscle fibers, which run vertically, are incised and turned
      90 degrees, so the edges of the platysma fibers are sutured to the edge of the
      residual orbicularis. The mucosal layer and the vermilion are reconstructed with
      a rotational flap from the cheek mucosa. The motor nerve and the vascular pedicle
      are preserved during the mobilization. The authors have treated six cases without
      relevant complication. A thorough knowledge of the anatomy of the region is
      mandatory; the surgical work must be precise and takes a long time, but results
      are highly satisfactory.

PMID- 9623821
TI  - Reasons why women who have mastectomy decide to have or not to have breast
      reconstruction.
AB  - Breast reconstruction after mastectomy is chosen by approximately 10 percent of
      Australian women. Younger women are more likely to have this surgical procedure.
      This suggests that there may be many factors determining this choice. Sixty-four
      women who wore an external postmastectomy breast prosthesis and 31 women who had
      postmastectomy breast reconstruction participated in the present study. The
      purpose was to gain a greater understanding through semi-structured interviews of
      why women who had breast reconstruction chose this alternative and why women who
      wore the external postmastectomy breast prosthesis elected not to have
      reconstruction. The study also ascertained how difficult it was for the women in
      both groups to decide their particular breast restoration alternative. The most
      frequently endorsed reasons for not having breast reconstruction in the
      prosthesis group included: (1) not essential for physical well being, (2) not
      essential for emotional well being, (3) not having enough information about the
      procedure, and (4) not wanting anything unnatural in the body. When each member
      of the group was asked to identify a major reason for not having reconstruction,
      two predominant issues emerged: (1) fearing complications and (2) perceiving
      themselves as being too old for the procedure. Twelve percent of the prosthesis
      group experienced difficulty in making the decision not to have reconstruction.
      Three factors accounted for this difficulty: (1) the lack of family support, (2)
      the inability to have a specific type of reconstruction, and (3) the perception
      that friends and acquaintances saw the surgery as cosmetic. The most frequently
      reported reasons given by the reconstruction group for having reconstruction
      included: (1) to get rid of the external breast prosthesis, (2) to be able to
      wear many different types of clothing, (3) to regain femininity, and (4) to feel
      whole again. The least influential factors were to improve marital and sexual
      relations. The major reason cited most often by this group was to feel whole
      again. None of the women in the reconstruction group experienced any difficulty
      when deciding their method of breast restoration. What factors are taken into
      consideration by women when they decide either to have or not to have
      reconstruction need to be understood by physicians. This knowledge will assist
      them in conveying appropriate information regarding alternatives and will help
      them deal with the women's concerns and/or misconceptions.

PMID- 9623822
TI  - A comparison of morbidity from bilateral, unipedicled and unilateral, unipedicled
      TRAM flap breast reconstructions.
AB  - A large series of women who had undergone bilateral, pedicled TRAM flap
      reconstructions were compared with women who had had unilateral, unipedicled TRAM
      flap procedures to determine whether a bilateral TRAM flap breast reconstruction
      had significant additional morbidity. The records of all women who underwent
      either a bilateral or unilateral pedicled TRAM flap breast reconstruction through
      the Emory Clinic from 1987 to 1994 (n = 257) were retrospectively analyzed with
      respect to general, breast (fat necrosis, flap loss, and cellulitis), and
      abdominal (hernia, skin loss, and cellulitis) complications. By using logistic
      regression, risk factors for these complications were determined. The incidence
      of fat necrosis and partial flap loss was not significantly different among
      bilateral patients compared with patients with unilateral TRAM reconstructions
      (10.0 percent versus 12.6 percent, p = 0.64 and 3.8 percent versus 5.5 percent, p
      = 0.74, respectively). The rate of hernia formation in the bilateral TRAM flap
      patients (5.4 percent) was similar to that of unilateral patients (3.9 percent, p
      = 0.80). Significant factors for any complication in both patient populations
      included obesity, smoking, and prior irradiation. The type of breast
      reconstruction was not a significant factor for any breast or donor-site
      complication. A bilateral TRAM reconstruction showed a weak association with
      general complications. Review of the Emory Clinic experience with unilateral and
      bilateral pedicled TRAM flap reconstructions from 1987 to 1994 was able to detect
      no significant additional rate of complications for bilateral pedicled TRAM flap
      breast reconstructions compared with unilateral unipedicled TRAM flap procedures.

PMID- 9623823
TI  - Fate of the TRAM flap after abdominoplasty in a rat model.
AB  - During a classical abdominoplasty, all musculocutaneous perforators from the deep
      inferior epigastric vessels are normally divided. Even if somehow
      neovascularization could relink the abdominal skin and rectus abdominis muscles,
      reestablishing these same discrete perforators would be unlikely because of the
      barrier effect of the abdominal wall fascia. Therefore, a lower transverse rectus
      abdominis musculocutaneous (TRAM) flap intuitively should not regain sufficient
      vascularity for viability after a prior abdominoplasty, and a history of the
      latter should be expected to be a major contraindication for this procedure.
      Nevertheless, anecdotal observations of successful lower TRAM flaps following
      abdominoplasty seem to contradict our basic principles, which may need better
      further elucidation. Consequently, this two-stage study in Sprague-Dawley rats
      was undertaken, initially performing an abdominoplasty in all rats. This was
      followed 1 or 10 months later by the creation of an unipedicled superiorly based
      TRAM flap that incorporated virtually all of the abdominal skin. From our
      identical historical TRAM flap control (n = 5) except without prior
      abdominoplasty, 72.8 +/- 12.83 percent of this area survived. TRAM flaps raised 1
      month after the abdominoplasty (n = 6) had 2.2 +/- 3.4 percent or essentially no
      viability. Unexpectedly, the long-term group (n = 7) demonstrated 13.7 +/- 10.0
      percent viability, ranging from 0 to 30 percent. Both groups of TRAM flaps after
      abdominoplasty had a flap survival area significantly less than that of the
      control by two-tailed group t test (p < 0.001), and that of the long-term group
      area was significantly greater than that of the short-term (p = 0.022). Lead
      oxide studies 10 months after abdominoplasty revealed no irrefutable evidence of
      the reestablishment of rectus abdominis perforators to the integument, although
      obviously some reconnections had formed at the microcirculatory level to
      partially revascularize some flaps. The range of viability of the long-term rat
      TRAM flaps documented that for the majority, surviving surface area was minuscule
      even following a delay equivalent to a human decade after abdominoplasty (1 rat
      month - 1.1 human years), yet rarely sufficient revascularization did indeed
      occur, which could explain the prior unusual clinical successes. However, the
      basic principle that a TRAM flap raised following a classical abdominoplasty at
      any time would be a risky maneuver seems to still be a valid concept.

PMID- 9623824
TI  - Silicon analysis of breast and capsular tissue from patients with saline or
      silicone gel breast implants: II. Correlation with connective-tissue disease.
AB  - The silicone breast implant controversy rages on. Recent work has demonstrated
      that normal or baseline breast tissue silicon levels in women who had had no
      prior exposure to any type of breast implant may be as high as 446 microg/gm of
      tissue. These data ranged from 4 to 446 microg/gm of tissue, with a median of
      27.0 microg/gm of tissue. In addition, numerous other epidemiologic and
      rheumatologic studies have demonstrated no association between silicone breast
      implants and any connective-tissue diseases. Despite these reports, the use of
      silicone implants remains restricted. The present study measured breast and
      capsular tissue silicon levels from 23 breasts in 14 patients with saline
      implants, and from 42 breasts in 29 patients with silicone implants. No patient
      in the saline implant group presented with signs or symptoms of connective-tissue
      disease. Patients with silicone implants, however, were divided into three groups
      based on the presence or absence of signs or symptoms of connective-tissue
      disease: group I, no symptoms or signs; group II, + symptoms, no signs; and group
      III, + symptoms, + signs. Six patients in group III were diagnosed with a
      specific connective-tissue disease, including systemic lupus erythematosus,
      rheumatoid arthritis, or scleroderma. The most common indications for implant
      removal or exchange were capsular contracture and implant rupture, although 41
      percent of patients with silicone implants expressed media-related concern over
      the implant issue. The most common symptoms described by patients in groups II
      and III were joint pain and stiffness, arm pain and numbness, and fatigue. In all
      groups, capsular tissue silicon levels were significantly greater than breast
      tissue levels. This finding may indicate that the capsule serves as a barrier to
      the distribution of silicone from the implant into adjacent breast tissue.
      Although breast tissue silicon levels in patients with silicone implants were not
      significantly greater than those in patients with saline implants (p = 0.48),
      capsular tissue levels in patients with silicone implants were, indeed,
      significantly greater than those in patients with saline implants (p < 0.001).
      However, no statistically significant differences in tissue silicon levels were
      observed with relation to the presence or absence of connective-tissue disease
      signs or symptoms in patients with silicone implants (groups I to III).
      Therefore, these data strengthen the conclusion that there is no association
      between tissue silicon levels and connective-tissue disease.

PMID- 9623825
TI  - Superior gluteal vessel as recipient for free flap reconstruction of lumbosacral
      defect.
AB  - When the lumbosacral soft-tissue defect cannot be closed with a local flap, the
      option of a free flap should be considered. However, very few cases of free flaps
      have been reported, the reason being mainly difficulties in finding a suitable
      recipient vessel. Several vessels, such as inferior gluteal vessel, extension of
      thoracodorsal vessel with vein graft were reported as recipient vessels, but each
      one had its own drawbacks. The superior gluteal vessel has been used as a donor
      vessel in breast reconstruction after mastectomy but is thought to be undesirable
      as a recipient for microvascular anastomosis, mainly because of technical
      difficulty. From May of 1993 to March of 1997, five patients (one man and four
      women) received microvascular transfer of latissimus dorsi myocutaneous flaps
      using the superior gluteal vessel as a recipient. Their ages ranged from 11 to 64
      years (mean 44 years of age). The causes of lumbosacral defects were tumor (1),
      trauma (1), radiation (2), and pressure sore (1). Before free flap transfer, the
      patients received an average of 2.8 operations for sacral lesions. Mean follow-up
      period was 12.4 months (2 to 40 months). A lateral approach was used to the
      superior gluteal vessel after elevation and retraction of gluteus maximus muscle.
      A thoracodorsal artery and vein were anastomosed to superior gluteal artery and
      vein in three cases, whereas in two cases, one artery and two veins could be
      anastomosed. All the flaps survived with complete recovery from sacral lesions.
      During the follow-up period, one case of partial skin graft necrosis and one case
      of a small superficial pressure sore developed, but there was neither dehiscence
      nor recurrence. The superior gluteal vessel is large in caliber, constant, with
      numerous branches, lying in proximity to the lesion, and relatively unaffected
      despite previous radiation. The technical difficulties with the deep location and
      short pedicle length can be overcome with some modifications in approach to the
      vascular pedicle. The superior gluteal artery and vein can be used as a recipient
      for the free tissue transfer when the lumbosacral defects cannot be covered with
      a conventional method.

PMID- 9623826
TI  - No correlation between activated protein C resistance and free flap failures in
      100 consecutive patients.
AB  - This study evaluates whether thrombophilic disorders contribute to failures in
      microvascular surgery. A recently discovered condition is focused on, i.e.,
      activated protein C resistance, which is a highly prevalent functional defect of
      a crucial endogenous anticoagulant system--the protein C anticoagulant pathway
      (up to 15 percent of Caucasians affected). One hundred consecutive patients were
      operated on with 103 free tissue transfers during a 2.5-year period, all of which
      received perioperative intravenous anticoagulation, principally based on dextran
      (1 liter) and a heparin bolus at vascular reperfusion (80 to 100 IU/kg). The
      patients underwent extensive laboratory analysis with respect to conditions
      predisposing for thrombosis. Eleven patients were found to be activated protein C
      resistant, and one patient had congenital protein S deficiency. There were six
      total and five partial flap losses, which, however, in only one case coincided
      with the presence of a thrombophilic disorder (activated protein C resistance).
      By contrast, a substantial portion of flap necroses could be related to
      nonconstitutional factors (for example, pedicle kinking). It is concluded that
      routine screening for hypercoagulable states such as activated protein C
      resistance is not necessary in microvascular surgery.

PMID- 9623827
TI  - Neurovascular supply of the gracilis muscle: a study in the monkey and human.
AB  - A comparison of the gross anatomy, extramuscular nerve branches, and
      intramuscular blood supply of the gracilis muscle showed similar patterns in both
      monkey and human. The number and pattern of distribution of the extramuscular
      terminal branches to the muscle were similar. The intramuscular neural pattern
      demonstrated with the Sihler's staining technique was also similar in both
      species. In vivo electrical stimulation studies in the monkey revealed that
      stimulating each extramuscular terminal nerve branch produced a distinct
      segmental contraction of the muscle. Independent contraction with force
      generation was observed when the monkey muscle was split into anterior and
      posterior segments and stimulated through each of the two subdivisions of the
      main nerve trunk to the muscle. Angiograms verified that circulation was
      preserved in these two segments.

PMID- 9623828
TI  - V-Y dorsal metacarpal flap: a new technique for the correction of syndactyly
      without skin graft.
AB  - A new technique for web reconstruction in congenital syndactyly is described.
      Twenty-one web spaces in 12 patients were treated using this method. The dorsal
      metacarpal flap was used as an island V-Y advancement to cover the newly created
      web space, thus avoiding skin graft in this space. A follow-up of 6 months to 2
      years showed neither recurrence of the deformity nor web creep of any degree. The
      operation is rapid, easy, and reproducible. It is suggested that this technique
      can be used in all types of syndactyly.

PMID- 9623829
TI  - The effect of bipolar electrocautery on peripheral nerves.
AB  - Although bipolar cautery was designed to minimize trauma to the central nervous
      system, little is known about the effects of bipolar cautery on peripheral nerve
      tissue. This experiment was designed to study the effect of direct bipolar
      cautery on a peripheral nerve and the muscles innervated by that nerve. Lewis
      rats (n = 200) were assigned to five different groups: control, sham, and three
      cautery groups (duration of either 0.5, 1.0, or 1.5 seconds). The hind limb
      tibial nerves were isolated in the sham group and isolated and cauterized in the
      cautery groups. Assessments performed at 2 hours, 2 weeks, 4 weeks, and 8 weeks
      postoperatively included isometric contractile function studies of both a fast-
      and a slow-twitch muscle, muscle weights, and nerve histology/morphometry.
      Significant muscle weight loss and reduced muscle function were found in the
      cautery groups at 2, 4, and 8 weeks (p < 0.05). Histologically, the nerves of the
      cautery groups showed nerve damage consistent with Sunderland's type 4 nerve
      injury when examined at 2 weeks and showed nerve regeneration at 4 and 8 weeks.
      Both the fast-twitch muscle and the shorter duration cautery were associated with
      faster recovery relative to the slow-twitch muscles and longer duration cautery,
      respectively. Bipolar cautery, as administered to rat tibial nerves in this
      experiment, is associated with a significant injury to the nerve and loss of
      function of the muscles innervated by the nerve.

PMID- 9623830
TI  - Nerve injection injury with botulinum toxin.
AB  - The therapeutic use of botulinum toxin (Botox) is increasing in popularity.
      Previous studies have shown that various drugs, especially when injected
      intrafascicularly, can cause major nerve damage. This study evaluates the
      potential for neurotoxicity of botulinum toxin in a rat sciatic nerve model.
      Lewis rats were randomly assigned to one of six groups (n = 10/group). Group 1,
      2, and 3 rats received, respectively, an intrafascicular, extrafascicular, and
      extraneural injection of 50 microl of botulinum toxin (50 UI/ml). Group 4, 5, and
      6 rats received 50 microl of 10% phenol as a positive control. Five animals
      received saline as a negative control. Animals were sacrificed at 2 and 7 weeks.
      Nerves were harvested and processed for histology and morphometry. Nerves in all
      botulinum toxin groups retained a normal architecture without cellular
      infiltration or demyelination. The number and diameter of fibers, the thickness
      of myelin, and the percentage of neural tissue were comparable with normal
      controls. Nerves injected intraneurally with phenol presented with severe damage,
      demyelination, and inflammation at 2 weeks and showed signs of early regeneration
      at 7 weeks. This study demonstrates that in a rat model, even direct intraneural
      injection of botulinum toxin caused no damage. This information should encourage
      the reconstructive surgeon to consider broader applications of this drug.

PMID- 9623831
TI  - Eicosanoids and inflammatory cells in frostbitten tissue: prostacyclin,
      thromboxane, polymorphonuclear leukocytes, and mast cells.
AB  - The pathophysiology of cold injury is still controversial. An inflammatory
      process has been implicated as the underlying mechanism and certain anti
      inflammatory substances such as ibuprofen and acetylsalicylic acid have been used
      in the clinical treatment of frostbite injury. It has been postulated that the
      progressive ischemic necrosis is secondary to excessive thromboxane A2
      production, which upsets the normal balance between prostacyclin (prostaglandin
      I2) and thromboxane A2. It was aimed to clarify the pathophysiology of cold
      injury in this study. Twenty-one New Zealand White rabbits, each weighing 1.2 to
      2.9 kg, were divided into control (n = 10) and frostbitten (n = 11) groups the
      randomly. The rabbit ears in the frostbitten group were subjected to cold injury,
      and the levels of thromboxane A2 (as thromboxane B2) and of prostaglandin I2 (as
      6-keto-prostaglandin F1alpha) and the number of inflammatory cells
      (polymorphonuclear leukocytes and mast cells) were measured in normal and
      frostbitten skin of rabbit ears. The levels of 6-keto prostaglandin F1alpha and
      thromboxane B2, the stable metabolites of prostaglandin I2 and thromboxane A2,
      respectively, were increased in a statistically significant way (p < 0.002) by
      frostbite injury; however, thromboxane B2 increased more than 6-keto
      prostaglandin F1alpha. Polymorphonuclear leukocytes and mast cells, absent in
      normal skin, were present in the frostbitten skin. There was a statistically
      significant (p < 0.01) correlation between the time a rabbit ear was maintained
      at below -10 degrees C and skin survival and between the weights of rabbits and
      skin survival (p < 0.024). All these findings suggest that inflammation is
      involved in frostbite injury; a decrease in prostaglandin I2/thromboxane A2 ratio
      could be one of the factors leading to necrosis; the bigger the animal, the
      better its ability to counter frostbite.

PMID- 9623832
TI  - Effects of calcitonin gene-related peptide on wound contraction in denervated and
      normal rat skin: a preliminary report.
AB  - The aim of the present study was to observe the effect of calcitonin gene-related
      peptide (CGRP) on wound contraction in both denervated and normal areas. A total
      of 100 Wistar rats, each of which had a 2 x 2 cm full-thickness skin defect on
      the back, were divided into two main control groups and six corresponding
      experimental groups in which 10 x 10(-9) M and 10 x 10(-12) M synthetic rat CGRP
      were given intraperitoneally and intradermally. Contraction was assessed weekly
      with planimetry, and mean surface areas (mm2 +/- SD) of related groups were
      compared. Complete closure took 4 weeks for the normal control group and 8 weeks
      for the denervated control group (p < 0.05). The 10 x 10(-12) M CGRP with both
      types of application showed a decrease in the length of time for complete closure
      to 3 weeks in the normal experimental groups (p < 0.05), but complete closure
      still took 4 weeks in normal groups in which 10 x 10(-9) M CGRP was given (p <
      0.05). Any dosage of CGRP given intraperitoneally showed no change in the closure
      period in the denervated experimental groups (p > 0.05). CGRP showed a trophic
      effect on healing by an increased rate of contraction in the rat model. However,
      the neural supply to the wound area seemed to be intact because of the necessity
      of axonal transfer of CGRP.

PMID- 9623833
TI  - Advantage of the presence of living dermal fibroblasts within in vitro
      reconstructed skin for grafting in humans.
AB  - Methods for serial cultivation of human keratinocytes can provide large
      quantities of epidermal cells, which have the potential of restoring the vital
      barrier function of the epidermis in extensive skin defects such as burns. To
      investigate the value of combining an epidermis with a dermal component,
      fibroblasts originated from the superficial dermis were used to seed a collagen
      lattice as described by E. Bell (dermal equivalent). Beginning in 1981, we
      grafted 18 patients (burns and giant nevi) using 35 grafts 10 x 10 cm in size. In
      the course of this work, the original technique was modified and improved as
      experience was gained. We began by using small skin biopsy samples as a source of
      keratinocytes cultured on a dermal equivalent before grafting in a one-step
      procedure, but this gave poor cosmetic results, because of a nonhomogeneous
      epidermalization. We then chose to cover the graft bed using a two-step
      procedure. The first step consisted of grafting a dermal equivalent to provide a
      dermal fibroblast-seeded substrate for subsequent in vivo epidermalization by
      cultured epidermal sheets. Whatever the epidermalization technique used, a living
      dermal equivalent applied to the graft bed was found to reduce pain, to provide
      good hemostasis, and to improve the mechanical and cosmetic properties of the
      graft. A normal undulating dermal-epidermal junction reappeared by 3 to 4 months
      after grafting and elastic fibers were detectable 6 to 9 months after grafting.
      As a result of the biosynthesis of these products, the suppleness (e.g.,
      elasticity) of the grafts was closer to that of normal skin than the cicatricial
      skin usually obtained with epidermal sheets grafted without the presence of
      living dermal cells. This rapid improvement of the mechanical properties of the
      graft could be attributed to the presence of fibroblasts cultured from the dermis
      and seeded into the collagen matrix.

PMID- 9623834
TI  - Dislocation of anatomic structures into the maxillary sinus after craniofacial
      trauma.

PMID- 9623835
TI  - Pyoderma gangrenosum of the breast: sequential grafting.

PMID- 9623836
TI  - Unusual complications of circumcision.

PMID- 9623837
TI  - Monobloc distraction osteogenesis during infancy: report of a case and
      presentation of a new device.

PMID- 9623838
TI  - Arced segmental mandibular regeneration by distraction osteogenesis.

PMID- 9623839
TI  - Computer planning for breast reconstruction by tissue expansion.

PMID- 9623840
TI  - An exploratory investigation of the morphology and biochemistry of cellulite.
AB  - Dimpling of the skin of the thighs and buttocks is commonly referred to as
      cellulite, and it afflicts women much more frequently than men. Whereas many
      therapies that presume cellulite is caused by an abnormality of adipose tissue
      have gained recent popularity, the basic pathophysiology of cellulite has not
      been clearly identified. Theoretically, cellulite could reflect differences in
      adipose tissue biochemistry or connective tissue structure of affected versus
      unaffected individuals and/or of affected versus unaffected regions within an
      individual. We report here on direct experimental examination of these
      possibilities. Seven healthy adult subjects (five women, two men; four affected,
      three unaffected) underwent sonography of the thigh, measurement of regional in
      vivo subcutaneous adipose tissue metabolism (catecholaminergic responsiveness and
      blood flow) by microdialysis probe studies of the abdomen and the thigh, and full
      thickness wedge biopsy of the thigh under local anesthesia. The presence of
      cellulite was defined as evidence of dimpling of the skin of the posterolateral
      thigh when the subject stood with the affected leg flexed to 90 degrees at the
      hip and knee. Any continuous area of skin at least 3 cm in diameter in which no
      dimpling was evident was designated as "unaffected." In all affected individuals,
      studies were performed to include both affected and unaffected areas of the
      thigh. In vitro pathologic examination of wedge biopsies and in vivo sonographic
      examination of the thigh both showed a diffuse pattern of extrusion of underlying
      adipose tissue into the reticular dermis in affected, but not unaffected,
      individuals. In vitro and in vivo studies also demonstrated that women had a
      diffuse pattern of irregular and discontinuous connective tissue immediately
      below the dermis, but this same layer of connective tissue was smooth and
      continuous in men. This connective tissue layer was more irregular and
      discontinuous in affected versus unaffected individuals. No significant
      differences were noted in subcutaneous adipose tissue morphology, lipolytic
      responsiveness, or regional blood flow between affected and unaffected sites
      within individuals. There is a sexual dimorphism in the structural
      characteristics of subdermal connective tissue that predisposes women to develop
      the irregular extrusion of adipose tissue into the dermis, which characterizes
      cellulite. These gender-related differences are diffuse and not localized only to
      affected areas. There is no evidence of any primary role for adipose tissue
      physiology, blood flow, or biochemistry in the etiology of cellulite, although
      the connective tissue of the female thigh is structured to accentuate differences
      in small subdermal adipose tissue depots.

PMID- 9623841
TI  - Enhancing the survival of aspirated human fat injected into nude mice.
AB  - Injection of aspirated fat is now the most commonly used technique for the
      filling of depressed areas. Partial absorption of the injected fat is the main
      limitation of this procedure. Cariel T.M. is an enriched serum-free cell culture
      medium, its ability to enhance the survival of human aspirated fat grafts was
      investigated in the nude mouse model. A volume of 0.75-cc Cariel preprocessed fat
      was injected under the scalp skin of 16 nude mice in the experimental group, and
      the same volume of saline preprocessed fat was injected to 15 control group of
      mice. Significant maintenance of the weight, 46 percent in the experimental group
      compared with 29 percent in the control group (p < 0.008), and the volume, 44
      percent in the experimental group compared with 31 percent in the control group
      (p < 0.026), was observed, after 15 weeks, in this newly used model. It seems
      that addition of the nutrients enriched with anabolic hormones enabled the
      survival and take of more adipose cells in the graft.

PMID- 9623842
TI  - Function of the nasal muscles in normal subjects assessed by dynamic MRI and EMG:
      its relevance to rhinoplasty surgery.
AB  - The external nose is generally considered to have a relatively static shape.
      Movement of the nose and the potential for change of external shape and the
      internal airway have been assessed by (1) cadaver dissection and (2) dynamic
      studies during a standardized series of facial expressions in 13 subjects; video
      recording of the movement of skin markers, electromyography, and moving magnetic
      resonance images. A standard description of muscle anatomy is presented. The
      dynamic investigations indicated the following. Video analysis showed the
      components of muscle action: dilatation, constriction of the nostril, depression
      of the tip, vertical contraction in the bridge, and elevation of the alar, in
      different expressions. Electromyography confirmed muscle actions during
      expression and phonation. Magnetic resonance imaging demonstrated large changes
      in the external shape of the nose and nasal aperture due to muscle actions.
      Muscle function should be given greater consideration in aesthetic and cleft
      rhinoplasty.

PMID- 9623843
TI  - Bigger is not always better: body image dissatisfaction in breast reduction and
      breast augmentation patients.
AB  - This study investigated body image dissatisfaction in breast reduction and breast
      augmentation patients. Thirty breast reduction and 30 breast augmentation
      patients completed two body image measures preoperatively. Breast reduction
      patients reported greater dissatisfaction with their overall body image as
      compared with breast augmentation patients, part of which can be understood as a
      function of their increased body weight. When asked specifically about their
      breasts, reduction patients displayed increased body image dysphoria and
      maladaptive behavioral change, including embarrassment about their breasts in
      public areas and social settings and avoidance of physical activity. Results are
      discussed in the context of ideal body weight cutoffs by third-party payers for
      reimbursement for breast reduction. Recommendations for reimbursement criteria
      that de-emphasize the role of body weight are made.

PMID- 9623844
TI  - Long-term advantages of permanent expandable implants in breast aesthetic
      surgery.
AB  - Permanent expandable implants are widely used in breast reconstructive surgery,
      but their use in aesthetic surgery is still uncommon. Previous reports on breast
      expansion-augmentation using permanent expandable implants focused on immediate
      and early advantages but failed to evaluate long-term benefits, because the
      reservoir was removed a few months after implantation and the ability to adjust
      the implant size was lost. Since 1986, we have used permanent expandable implants
      in 129 women for unilateral or bilateral breast augmentation using the following
      approach: implants were positioned submuscularly through a transaxillary
      incision; the filling port was placed a few centimeters below the incision and
      permanently retained; the implants were positioned underinflated and then
      overexpanded starting 2 weeks after implantation; after a period of
      overinflation, deflation to the preoperatively planned volume was scheduled;
      patients' suggestions regarding final volume adjustments were followed; the
      effects of repeated overinflations and deflations were investigated in several
      different conditions. Permanent expandable implants offer unique long-term
      technical and psychological advantages in the management of highly demanding
      patients and in the following clinical situations: pregnancy, impending capsular
      contracture, contralateral progressive ptosis, tubular breasts(s), difficult
      mammographic examination, spontaneous deflation, and rippling. Disadvantages
      include economical cost, port-related problems, and repeated requests by patients
      for volume changes. Saline permanent expandable implants allowed less flexibility
      in adjusting the breast size and caused discomfort when overexpanded. Permanent
      expandable implants in breast aesthetic surgery offer several advantages, and
      because patients can play an active role in deciding volume adjustments,
      compliance is very high.

PMID- 9623845
TI  - Residency training in aesthetic surgery: maximizing the residents' experience.
AB  - Plastic surgery residency programs often rely on a residents' aesthetic clinic to
      help train residents in aesthetic surgery. The television media may be used to
      help boost interest in such clinics. We report our experience with a local
      television station in helping to produce a "health segment" broadcast that
      chronicled the experience of an aesthetic patient in the residents' aesthetic
      clinic. As a result of this broadcast, approximately 150 people responded by
      telephone and subsequently attended a series of seminars designed to screen
      patients and educate the audience about the aesthetic clinic. A total of 121
      patients (112 women and 9 men) signed up for personal consultations. The age
      distribution and requested procedures are presented. From the data, we conclude
      that there is a healthy demand for reduced-fee plastic surgery procedures
      performed by residents in plastic surgery. The number and variety of cases
      generated are sufficiently diverse to provide a well-rounded operative
      experience. The pursuit of media coverage of a not-for-profit clinic has the
      potential for generating large patient volume. Such efforts, although very
      attractive, are not without their own risks, which must be taken into
      consideration before engaging the media in the public interest arena.

PMID- 9623846
TI  - Eyelash reconstruction and aesthetic augmentation with strip composite sideburn
      graft.

PMID- 9623847
TI  - Omiderm: an inexpensive dressing after CO2 laser resurfacing.

PMID- 9623848
TI  - Enough.

PMID- 9623849
TI  - SoftForm facial implants. Plastic Surgery Educational Foundation DATA Committee.
      Device and Technical Assessment.

PMID- 9623850
TI  - Uncircumcision: a historical review of preputial restoration.
AB  - Throughout history, demands for restoration of the prepuce after circumcision
      were most commonly related to the political or religious persecution of the
      Jewish people. The first evidence for such a procedure is mentioned in the Bible:
      Under the reign of Antiochus IV (168 BC) Hellenistic ideals, such as public
      nakedness at athletic games or in public baths, emerged in Judea and forced Jews
      to stretch their shortened foreskins with a special weight, the Pondus Judaeus,
      to cover the glans (I. Maccabees 1). Similar efforts are reported in the Talmud
      during the time of Hadrian (132 AD). Celsius (25 BC-50 AD) was the first to give
      a detailed description of two surgical techniques for uncircumcision in his De
      medicina libri octo. Subsequent works, for example by Galen (131-200 AD) and
      Paulus Aeginata in the seventh century, only contained a repetition of these
      methods without presenting any new aspects. Ambroise Pare gave a new impetus in
      the sixteenth century, suggesting the insertion of a catheter into the distal
      urethra to guarantee free passage of urine during postoperative healing. In this
      past century, Johann Friedrich Dieffenbach was the first to dedicate a whole
      chapter to the problem of "posthioplastice" in a modern textbook of plastic
      surgery. Almost no written documents exist of uncircumcision during the Nazi era;
      nevertheless, surgical treatment seemed to be widespread as every circumcised man
      was in danger of being denounced as a Jew. Personal reports of patients and
      doctors performing surgical restoration of the prepuce are presented. Nowadays,
      reports on surgical foreskin restoration are still rare and alternative methods
      of nonsurgical skin-expansion have become more common. Several organizations were
      founded in America against routine infant circumcision and give advice to
      foreskin restoration seekers.

PMID- 9623851
TI  - "Will the real plastic surgeon please stand up?".

PMID- 9623852
TI  - "Will the real plastic surgeon please stand up?".

PMID- 9623853
TI  - "Will the real plastic surgeon please stand up?".

PMID- 9623854
TI  - "Will the real plastic surgeon please stand up?".

PMID- 9623855
TI  - "Will the real plastic surgeon please stand up?".

PMID- 9623856
TI  - "Will the real plastic surgeon please stand up?".

PMID- 9623857
TI  - "Graduate medical education in plastic surgery".

PMID- 9623858
TI  - Endoscopic forehead lifts: the postoperatively adjustable technique.

PMID- 9623860
TI  - Nasal sarcoidosis.

PMID- 9623859
TI  - Endoscopic forehead fixation with histoacryl.

PMID- 9623861
TI  - Obtaining a perfectly circled areolar perimeter after reduction mammaplasty.

PMID- 9623862
TI  - Clinical confirmation that the nipple areola complex relies solely on the dermal
      plexus.

PMID- 9623863
TI  - Treatment of recalcitrant verrucae with both the ultrapulse CO2 and PLDL pulsed
      dye lasers.

PMID- 9623864
TI  - An interesting urethral fistula mechanism.

PMID- 9623865
TI  - Treatment of partial losses of the helix.

PMID- 9623866
TI  - The abdominal arteriovenous cross-flow flap of the rat.

PMID- 9623867
TI  - Chain-linked directional vascular plexuses of the integument and link-pattern
      vascularized flaps in distal extremities.

PMID- 9623868
TI  - Arteriovenous shunts for hemodialysis.

PMID- 9623869
TI  - Endoscopically assisted suction evacuation in the surgical treatment of
      subcutaneous hematomas.

PMID- 9623870
TI  - The "managed-care-tormented-university-based dwindling-reconstructive
      cosmetically enhanced practice".

PMID- 9623871
TI  - Addendum to "How to block and tackle the face".

PMID- 9623872
TI  - Psychosomatic research in end-stage renal disease: a framework for matching
      patient to treatment.

PMID- 9623873
TI  - Somatization--future perspectives on a common phenomenon.

PMID- 9623874
TI  - The relationship between daily stress and symptoms of irritable bowel: a time
      series approach.
AB  - Irritable bowel syndrome (IBS), a chronic disorder that includes symptoms such as
      abdominal pain and altered bowel habits, affects up to 22% of people in Western
      populations. The causes of IBS are not well understood, but are believed to be
      multifactorial. Although stress is widely believed to be implicated, empirical
      evidence in support of this is lacking, perhaps because a typical between
      participants analysis ignores individual differences and therefore may obscure
      any link. The present study used a within-person, lagged time-series approach to
      investigate the links between everyday stress and symptomatology in 31 IBS
      sufferers. Both everyday stress and symptomatology exhibited serial dependence
      for a statistically significant proportion of sufferers. Multiple regression
      analysis carried out on same-day and lagged relationships up to and including 4
      days found that, for over half the participants, everyday stress and symptoms
      were related. The best regression model was one in which symptoms were a function
      of hassles and symptoms on the previous 2 days, and hassles on the same day,
      fitting the data for 67% of participants. This prospective study confirms other
      studies that have suggested stress is a significant factor in IBS, and concludes
      that stress management programs may be both useful and cost-effective in the
      treatment of IBS.

PMID- 9623875
TI  - Psychological distress in patients with chronic, nonalcoholic, uncomplicated
      liver disease.
AB  - To study whether the presence of significant disease in a major organ, possibly
      with minimal or no clinical symptoms, would be associated with psychological
      disturbance, 80 subjects suffering from chronic hepatitis or cirrhosis, of
      nonalcoholic etiology were interviewed. Of these, 64 had either minimal or no
      physical symptoms. Patients completed the Brief Symptom Inventory (BSI) and the
      Impact of Event Scale (IES), questionnaires, which measure symptoms of
      psychological distress. It was found that 50% of the liver subjects were defined
      as cases by the BSI criteria including 15% who were defined as severe cases.
      There were no gender differences. Forty-five percent of asymptomatic liver
      subjects were defined as cases. Psychological distress was significantly
      pronounced in subjects with less than 12 years of education. This study points to
      a significant incidence of psychological distress, even in clinically
      asymptomatic subjects, suffering from chronic, nonalcoholic, uncomplicated liver
      disease.

PMID- 9623876
TI  - The impact of stressful life events on exacerbation of chronic low-back pain.
AB  - The impact of stressful life events on the development and onset of chronicity of
      low-back pain is not yet fully understood. Sixty-four consecutive patients with
      chronic low-back pain treated at the orthopedic out-patient unit of the Innsbruck
      University Hospital were investigated with regard to stressful life events.
      Patients were classified into two groups: one group consisting of patients whose
      pain had an organic etiology (n= 16), and another group consisting of those with
      pain of uncertain origin (idiopathic group, n=48). A method combining a
      semistructured interview with a self-assessment of the severity of stress caused
      by life events was employed for assessing the impact of such events on chronic
      low-back pain. In comparison to the patient group having organic causes of pain,
      the idiopathic group showed significantly more patients having at least one
      highly stressful event preceding the last substantial aggravation of pain
      (p=0.028). The latter group experienced significantly more exhaustion (p=0.016)
      and significantly more difficulties in active coping (p=0.011) when confronted
      with stressful life events. Stressful life events that arouse feelings of
      helplessness may contribute to the development of chronic idiopathic low-back
      pain. Our results emphasize the importance of investigating the subjective
      meaning and appraisal of stressful life events, taking into consideration both
      individual predisposition and psychosocial resources available to the patient.
      Finally, it is also important that the attending physician be aware of any life
      event that is particularly stressful for the patient so that psychosocial help be
      made available at the appropriate time.

PMID- 9623877
TI  - Long-term outcome of children and adolescents with anorexia nervosa: study of
      comorbidity.
AB  - Eighty-seven children and adolescents with anorexia nervosa, admitted to the
      Gaslini Department of Child Neurology and Psychiatry between 1976 and 1990, were
      followed up after a mean of 9.6 years. Outcome measures included the Morgan
      Russell Outcome Schedule as modified by Jeammet. Outcome was good in 43 (53%)
      cases, intermediate in 27 (34%) cases, and negative in 11 (14%) cases. No deaths
      occurred. Based on the Jeammet assessment schedule, the most significant items
      predicting outcome were insight; sexual, familial, and social relationships; and
      mental state. Gender of patients and early disease onset did not seem to be
      predictive measures. Poor outcome was associated with a severe initial clinical
      picture and length of in-patient treatment. In regard to comorbidity, mood and
      personality disorders seemed to be negative prognostic indicators, whereas
      anxiety disorders did not show prognostic value.

PMID- 9623878
TI  - Illness perceptions, coping and functioning in patients with rheumatoid
      arthritis, chronic obstructive pulmonary disease and psoriasis.
AB  - The present cross-sectional study analyzed the extent to which illness
      perceptions and coping strategies (as measured by the Illness Perception
      Questionnaire and the Utrecht Coping List, respectively) are associated with
      levels of daily functioning, as indicated by the Medical Outcomes Study SF-20,
      and disease-specific measures in 244 adults: 84 with rheumatoid arthritis (RA);
      80 with chronic obstructive lung disease (COPD); and 80 with psoriasis. The
      results of stepwise regression analyses indicated that a strong illness identity,
      passive coping, belief in a long illness duration, belief in more severe
      consequences, and an unfavorable score on medical variables were associated with
      worse outcome on disease-specific measures of functioning and on general role and
      social functioning. Coping by seeking social support and beliefs in
      controllability/curability of the disease were significantly related to better
      functioning. The implications of these findings for future interventions and
      research are discussed.

PMID- 9623879
TI  - Low education, high GP consultation rates: the effect of psychosocial factors.
AB  - The purpose of this study was to estimate the contribution of psychosocial
      factors to the increased use of a general practitioner (GP) among those with a
      lower level of education. The use of GP services was elicited from survey data
      from 2867 respondents from the Dutch Longitudinal Study on Socio-Economic
      Differences in the Utilization of Health Services (LS-SEDUHS) using a simple
      "Yes/ No" format. Psychosocial variables included long-term stressful conditions,
      social support, external locus of control, coping styles, and tendency to consult
      (a measure of people's propensity to go to a doctor with health problems). People
      with primary education used the GP services more than people with higher
      vocational training or a university degree (OR 1.87, p<0.05), adjusted for health
      status and health insurance. Only tendency to consult partially explained this
      difference (OR: 1.74, p>0.05). Most psychosocial factors do not seem very
      important in explaining high GP utilization rates among those with a low
      socioeconomic status. Alternative explanations are discussed.

PMID- 9623880
TI  - The effects of photic driving on mood states.
AB  - The EEG photic driving response is a sensitive neurophysiological measure. It has
      been used to assess drug effects, forms of epilepsy, neurological status of
      Alzheimer's patients, and physiological arousal. Photic driving also impacts the
      psychological status of a person by producing increased visual imagery and
      decreased physiological and subjective arousal. In this study, ten volunteers
      underwent nocturnal polysomnography followed by six daytime testing sessions. The
      six sessions consisted of the alpha attenuation test, two visual analog scales
      for mood, the Stanford Sleepiness Scale, photic stimulation, and the multiple
      sleep latency test. These tests were administered 2 hours upon awakening and
      every 2 hours thereafter. The mean mood across the six daytime testing sessions
      was computed for all mood variables pre- and post-photic stimulation. Significant
      differences were found for the subjective moods "sleepy," "alert," and "effort."
      However, no significant differences were found for pre- and post-photic driving
      for "angry," "irritable," "hungry," "tense," "overall," "happy," "sexual," and
      "sad." Additionally, all participants reported increased visual imagery during
      photic driving, as measured by their responses to an imagery questionnaire.

PMID- 9623881
TI  - The 2-5A system: modulation of viral and cellular processes through acceleration
      of RNA degradation.
AB  - The 2-5A system is an RNA degradation pathway that can be induced by the
      interferons (IFNs). Treatment of cells with IFN activates genes encoding several
      double-stranded RNA (dsRNA)-dependent synthetases. These enzymes generate 5'
      triphosphorylated, 2',5'-phosphodiester-linked oligoadenylates (2-5A) from ATP.
      The effects of 2-5A in cells are transient since 2-5A is unstable in cells due to
      the activities of phosphodiesterase and phosphatase. 2-5A activates the
      endoribonuclease 2-5A-dependent RNase L, causing degradation of single-stranded
      RNA with moderate specificity. The human 2-5A-dependent RNase is an 83.5 kDa
      polypeptide that has little, if any, RNase activity, unless 2-5A is present. 2-5A
      binding to RNase L switches the enzyme from its off-state to its on-state. At
      least three 2',5'-linked oligoadenylates and a single 5'-phosphoryl group are
      required for maximal activation of the RNase. Even though the constitutive
      presence of 2-5A-dependent RNase is observed in nearly all mammalian cell types,
      cellular amounts of 2-5A-dependent mRNA and activity can increase after IFN
      treatment. One well-established role of the 2-5A system is as a host defense
      against some types of viruses. Since virus infection of cells results in the
      production and secretion of IFNs, and since dsRNA is both a frequent product of
      virus infection and an activator of 2-5A synthesis, the replication of
      encephalomyocarditis virus, which produces dsRNA during its life cycle, is
      greatly suppressed in IFN-treated cells as a direct result of RNA decay by the
      activated 2-5A-dependent RNase. This review covers the organic chemistry,
      enzymology, and molecular biology of 2-5A and its associated enzymes. Additional
      possible biological roles of the 2-5A system, such as in cell growth and
      differentiation, human immunodeficiency virus replication, heat shock,
      atherosclerotic plaque, pathogenesis of Type I diabetes, and apoptosis, are
      presented.

PMID- 9623882
TI  - Cisplatin resistance in cyclic AMP-dependent protein kinase mutants.
AB  - The emergence of cisplatin resistance poses a major problem to the successful
      treatment of a variety of human malignancies. Therefore, understanding the
      molecular mechanisms that underlie cisplatin resistance could significantly
      improve the clinical efficacy of this cytotoxic agent. Various studies have
      described that cellular sensitivity to cisplatin can be influenced by several
      signal transduction pathways. In this review, we examine the role of the cyclic
      AMP-dependent protein kinase (PKA) in the modulation of drug resistance in
      cancer. By a somatic mutant genetic approach, the role of PKA in the development
      of resistance to chemotherapeutic agents has been investigated. A series of
      mutants with decreased PKA activity was examined for their sensitivity to
      cisplatin. PKA mutants with defective regulatory (RIalpha) subunits, but not
      altered catalytic (C) subunits, exhibit increased resistance to cisplatin, as
      well as other DNA-damaging agents. Furthermore, since RIalpha subunit mutants
      show enhanced DNA repair we, therefore, hypothesize that functional inactivation
      of PKA may result in increased recognition and repair of cisplatin lesions.
      Alternatively, it seems likely that mutation of the RIalpha subunit may affect
      cellular sensitivity to various anticancer drugs, suggesting that the RIalpha
      subunit may have other physiological functions in addition to inhibiting the
      kinase activity of the C subunit. Therefore, exploitation of cyclic AMP levels or
      functional alteration of the R subunit may potentiate the cytotoxicity of
      chemotherapeutic agents and circumvent drug resistance in cancer. More
      importantly, the altered pattern and mechanism of drug resistance may offer the
      opportunity to investigate novel regulatory functions of the RIalpha subunit of
      PKA.

PMID- 9623884
TI  - Developmental neuronal death is not a universal phenomenon among cell types in
      the chick embryo retina.
AB  - The goal of this study was to investigate whether all the cell types present in
      the chick embryo retina undergo developmental neuronal death. Apoptosis was
      investigated in retinal sections at different developmental stages, processed
      either with propidium iodide, which stains pyknotic nuclei intensely, or with
      terminal transferase-mediated deoxyuridine triphosphate (d-UTP)-biotin nick-end
      labeling (TUNEL). Internucleosomal DNA fragmentation was investigated in tissue
      extracts by agarose gel electrophoresis. TUNEL-positive (T+) cells and pyknotic
      nuclei were first detectable in the ganglion cell layer (GCL) around embryonic
      day (ED) 8 and peaked at ED 10. In the inner nuclear layer (INL), T+ and pyknotic
      cells first appeared on ED 8, reached maximum frequency on ED 11, and were
      largely absent after ED 14. DNA ladders were observed at all the stages, when T+
      and pyknotic cells were abundant, but not on ED 4, when only scattered dead cells
      were observed histologically. Dying cells were virtually never detected in the
      outer nuclear layer (ONL) from ED 4 to postnatal day 2. After unilateral midbrain
      ablation on ED 5, there was a striking increase in the number of pyknotic and T+
      cells in both the GCL and in the INL of the contralateral eye but not in the ONL.
      The absence of apoptotic cell death in the ONL during normal development and
      after tectal ablation shows that developmental death is not universal among the
      various cell populations present in the chick embryo retina and raises questions
      regarding mechanisms controlling both photoreceptor survival and the matching of
      pre- and postsynaptic elements in the outer plexiform layer of this species.

PMID- 9623883
TI  - Heat-shock proteins in axoplasm: high constitutive levels and transfer of
      inducible isoforms from glia.
AB  - To characterize heat-shock proteins (HSPs) of the 70-kDa family in the crayfish
      medial giant axon (MGA), we analyzed axoplasmic proteins separately from proteins
      of the glial sheath. Several different molecular weight isoforms of constitutive
      HSP 70s that were detected on immunoblots were approximately 1-3% of the total
      protein in the axoplasm of MGAs. To investigate inducible HSPs, MGAs were heat
      shocked in vitro or in vivo, then the axon was bathed in radiolabeled amino acid
      for 4 hours. After either heat-shock treatment, protein synthesis in the glial
      sheath was decreased compared with that of control axons, and newly synthesized
      proteins of 72 kDa, 84 kDa, and 87 kDa appeared in both the axoplasm and the
      sheath. Because these radiolabeled proteins were present in MGAs only after heat
      shock treatments, we interpreted the newly synthesized proteins of 72 kDa, 84
      kDa, and 87 kDa to be inducible HSPs. Furthermore, the 72-kDa radiolabeled band
      in heat-shocked axoplasm and glial sheath samples comigrated with a band
      possessing HSP 70 immunoreactivity. The amount of heat-induced proteins in
      axoplasm samples was greater after a 2-hour heat shock than after a 1-hour heat
      shock. These data indicate that MGA axoplasm contains relatively high levels of
      constitutive HSP 70s and that, after heat shock, MGA axoplasm obtains inducible
      HSPs of 72 kDa, 84 kDa, and 87 kDa from the glial sheath. These constitutive and
      inducible HSPs may help MGAs maintain essential structures and functions
      following acute heat shock.

PMID- 9623885
TI  - Cadherin expression in the retina and retinofugal pathways of the chicken embryo.
AB  - The expression of two calcium-dependent adhesion molecules of the cadherin
      superfamily (cadherin-6B and cadherin-7) was mapped in the embryonic neural
      retina and retinofugal pathways of the chicken embryo and compared with the
      expression of R-cadherin, N-cadherin, and B-cadherin, studied previously. Whereas
      B-cadherin is only found in Miller glia, the other four cadherins are each
      expressed by specific subpopulations of retinal neurons. For example, different
      (but partly overlapping) populations of bipolar cells express R-cadherin,
      cadherin-6B, and cadherin-7. Cadherin-6B and cadherin-7 are also expressed by
      subsets of amacrine cells. In the inner plexiform layer, cadherin-6B and cadherin
      7 immunoreactivities are restricted to specific sublaminae associated with
      synapsin-I-positive nerve terminals. In addition, cadherin-6B and cadherin-7 are
      expressed by a subset of ganglion cells that project to several retinorecipient
      nuclei forming part of the accessory optic system (e.g., nucleus of the basal
      optic root and external pretectal nucleus). Together with their connecting fiber
      tracts, these nuclei also express cadherin-6B and cadherin-7 in their neurons and
      neuropile. The expression patterns of the two cadherins overlap but show distinct
      differences. Some other visual nuclei express cadherin-7 but not cadherin-6B. The
      expression patterns differ from those previously described for N- and R-cadherin.
      Together, these results demonstrate that cadherins could provide a system of
      adhesive cues that specify developing retinal circuits and other functional
      connections and subsystems in the embryonic chicken visual system.

PMID- 9623886
TI  - Programmed cell death is a universal feature of embryonic and postnatal
      neuroproliferative regions throughout the central nervous system.
AB  - During central nervous system (CNS) development, programmed cell death (PCD) has
      been viewed traditionally as a fate reserved for differentiating neurons that are
      in the process of making synaptic connections. Recent studies in the embryonic
      cerebral cortex (Blaschke et al. [1996] Development 122:1165-1174), however, have
      shown that many neuroblasts in the proliferative ventricular zone undergo PCD as
      well and that this likely represents a novel form distinct from that found in
      regions of postmitotic neurons. To determine the commonality of this form of PCD
      throughout the CNS, the prevalence of dying cells identified by in situ end
      labeling plus (ISEL +; Blaschke et al. [1996]) was determined within populations
      of proliferating neuroblasts that were identified by rapid bromodeoxyuridine
      incorporation. Based on this approach, dying cells were observed to be a common
      feature of all proliferative neuroblast populations examined. In addition, when
      ISEL+ was combined with in situ hybridization for postmitotic neural gene-1 (png
      1; Weiner and Chun [1997] J. Comp. Neurol. 381:130-142), which identifies newly
      postmitotic neurons, a positive correlation was found between the start of
      differentiation and the onset of PCD. These data indicate that PCD in neuroblast
      proliferative zones is a universal feature of nervous system development.
      Moreover, cell death represents a prominent cell fate that may be linked to
      mechanisms of differentiation.

PMID- 9623887
TI  - Neuronal and glial localization of GAT-1, a high-affinity gamma-aminobutyric acid
      plasma membrane transporter, in human cerebral cortex: with a note on its
      distribution in monkey cortex.
AB  - High-affinity gamma-aminobutyric (GABA) plasma membrane transporters (GATs)
      influence the action of GABA, the main inhibitory neurotransmitter in the human
      cerebral cortex. In this study, the cellular expression of GAT-1, the main
      cortical GABA transporter, was investigated in the human cerebral cortex by using
      immunocytochemistry with affinity-purified polyclonal antibodies directed to the
      C-terminus of rat GAT-1. In temporal and prefrontal association cortex
      (Brodmann's areas 21 and 46) and in cingulofrontal transition cortex (area 32),
      specific GAT-1 immunoreactivity (ir) was localized to numerous puncta and fibers
      in all cortical layers. GAT-1+ puncta were distributed homogeneously in all
      cortical layers, although they were slightly more numerous in layers II-IV, and
      appeared to have a preferential relationship to the somata and proximal dendrites
      of unlabeled pyramidal cells, even though, in many cases, they were also observed
      around nonpyramidal cells. Electron microscopic observations showed that GAT-1+
      puncta were axon terminals that formed exclusively symmetric synapses. In
      addition, some distal astrocytic processes also contained immunoreaction product.
      Analysis of the patterns of GAT-1 labeling in temporal and prefrontal association
      areas (21 and 46), in cingulofrontal transition areas (32), and in somatic
      sensory and motor areas (1 and 4) of the monkey cortex revealed that its
      distribution varies according to the type of cortex examined and indicated that
      the distribution of GAT-1 is similar in anatomically corresponding areas of
      different species. The present study demonstrates that, in the human homotypical
      cortex, GAT-1 is expressed by both inhibitory axon terminals and astrocytic
      processes. This localization of GAT-1 is compatible with a major role for this
      transporter in GABA uptake at GABAergic synapses and suggests that GAT-1 may
      contribute to determining GABA levels in the extracellular space.

PMID- 9623888
TI  - Morphological differences between fast and slowly adapting lingual afferent
      terminations in the principal and oral nuclei in the cat.
AB  - Previous studies indicated that fast-adapting (FA) and slowly adapting (SA)
      mechanoreceptive afferents innervating the facial or intraoral structures give
      rise to morphologically distinct terminal arbors in the individual subdivisions
      of the trigeminal sensory nuclear complex. The present study examined the
      collateral morphologies of lingual afferents in the nuclei principalis (Vp) and
      oralis (Vo) of the cat. Seven FA and six SA lingual afferents were
      physiologically characterized and stained by the intra-axonal horseradish
      peroxidase (HRP) injection technique. The two types of afferents established
      terminal arbors in the dorsomedial subdivision (Vpd) of the Vp, and the
      rostrodorsomedial (Vo.r) and dorsomedial subdivisions (Vo.dm) of the Vo, but the
      collateral morphologies are different between the two types. The FA afferents
      gave rise to mediolaterally extended oblong arbors in each subdivision, but the
      arbors were better developed in the Vo.r than in the Vpd and Vo.dm. The number of
      collaterals, intercollateral distance, number of boutons per collateral, and
      bouton size were also different among the subdivisions. The SA afferents were
      divided into two subtypes; one had a preferential projection into the Vpd or the
      Vo.r and Vo.dm, and others lacked a selected projection. Although the shape of
      their arbors varied from a stringy form to a roundish form, the general profile
      was denser, better developed, and rounder than that of FA afferents in each
      subdivision. The intercollateral distance and bouton size were different among
      the subdivisions. The number of boutons per collateral, bouton density, and
      bouton size were larger in SA than FA afferents in each subdivision. The present
      study demonstrated that two functionally distinct lingual afferents manifest
      unique morphological differences in the Vpd and Vo.

PMID- 9623889
TI  - Functionally and anatomically segregated visual pathways in the lobula complex of
      a calliphorid fly.
AB  - In dipteran insects, the lobula plate neuropil provides a major efferent supply
      to the premotor descending neurons that control stabilized flight. The lobula
      plate itself is supplied by two major parallel retinotopic pathways from the
      medulla: small-field, magnocellular afferents that are implicated in achromatic
      motion processing and Y cells that connect the medulla with both the lobula plate
      and the lobula. A third pathway from the medulla involves transmedullary (Tm)
      neurons, which provide inputs to palisades of small-field neurons in the lobula.
      Although, in their passage to the brain, many output neurons from the lobula
      plate are separated physically from their counterparts in the lobula, there is an
      additional class of lobula complex output neurons. This group is composed of
      retinotopic lobula plate-lobula (LPL) and lobula-lobula plate (LLP) cells, each
      of which has dendrites in both the lobula and the lobula plate. The present
      account describes the anatomy and physiology of exemplars of LPL and LLP neurons,
      a wide-field tangential neuron that is intrinsic to the lobula complex, and
      representatives of the Tm- and Y-cell pathways. We demonstrate novel features of
      the lobula plate, which previously has been known as a motion-collating neuropil,
      and now also can be recognized as supporting direction- or nondirection-specific
      responses to local motion, encoding of contrast frequency, and processing of
      local structural features of the visual panorama.

PMID- 9623890
TI  - Four retinal ganglion cell types that project to the superior colliculus in the
      thirteen-lined ground squirrel (Spermophilus tridecemlineatus).
AB  - The morphology of retinal ganglion cells projecting to the superior colliculus
      (SC) of the thirteen-lined ground squirrel (Spermophilus tridecemlineatus) was
      studied after retrogradely labeling the cells with cholera toxin subunit B. On
      the basis of previous reports, labeled cells were classified as small (6-10
      microm in soma diameter), medium (11-14 microm), or large (>14 microm). A total
      of 3,427 cells were studied. Small cells constituted 78% of the population, 21%
      were medium cells, and only 1% were classified as large. The morphology of medium
      sized cells was studied in more detail because large cells were few in number and
      the staining of the dendritic tree of small cells was not optimal. The best
      labeled medium-sized cells were classified on the basis of the shape and size of
      their dendritic tree and the pattern of dendritic ramification. Four types were
      identified among the medium-sized ganglion cells. Two types were classified as
      symmetric delta-like and asymmetric delta-like cells considering the relative
      symmetric or asymmetric distribution of their dendritic branches and their
      similarities with the delta type of the cat. Approximately 52% of all the medium
      sized cells studied were symmetrical delta-like, and 19% were classified as
      asymmetrical delta-like. These cells were also very similar to the symmetrical
      and asymmetrical directionally selective ganglion cells described in rabbit
      retina. Other cells were termed beta-like. They had the smallest dendritic tree
      diameter, and their tree size seemed to be related to retinal eccentricity.
      Medium beta-like cells comprised approximately 21% of all cells projecting to the
      SC. The fourth type was termed "acute angle" because most of their dendritic
      branches were relatively straight and formed acute angles (10-45 degrees) at
      their branching points. These cells were few in number (approximately 8% of all
      medium-sized cells studied) and did not resemble any reported previously in cats.
      Thus, a variety of morphological types of retinal ganglion cells projected to the
      SC. Of these, the symmetrical and asymmetrical delta-like cells appeared to
      correspond to the directionally selective type described in the ground squirrel
      (Michael, C.R. [1968] J. Neurophysiol. 31:257-267) and reported in the rabbit
      retina.

PMID- 9623891
TI  - Arborisation and termination of single motor thalamocortical axons in the rat.
AB  - The aim of this study was to examine the arborisations and terminations of
      individual thalamocortical axons in the motor system of the rat. Small,
      extracellular injections of an anterograde tracer (dextran-biotin) were made into
      the ventrolateral (VL) or ventral posterolateral (VPL) thalamic nuclei to label
      thalamocortical projections. Eleven motor axons and one somatosensory axon were
      reconstructed through serial sections just rostral from the injection site to
      their terminations in sensorimotor cortex. The smallest arbor arising from a
      single motor axon extended approximately 0.9 mm rostrocaudal and 0.9 mm
      mediolateral, the largest extended 3.9 mm rostrocaudal and 1.0 mm mediolateral.
      In some cases, two distinct plexuses of terminals were formed by an axon. In
      addition, motor axons formed terminals in cortical layer V only or in layers I,
      III, and V. By contrast (and in keeping with previous reports), the somatosensory
      axon formed a single plexus of terminals in layer IV of the cortex that extended
      approximately 0.3 mm rostrocaudal and 0.4 mm mediolateral. It is concluded that
      individual motor thalamocortical neurones are in a position to influence much
      more widespread cortical regions than somatosensory thalamocortical neurones.

PMID- 9623892
TI  - Differential distribution of Shaker-like and Shab-like K+-channel subunits in
      goldfish retina and retinal bipolar cells.
AB  - The distributions of Shaker subfamily Kv1.1 and Kv1.2 and Shab subfamily Kv2.1
      subunits of voltage-gated K+ channels were determined in the retina and ON
      bipolar cells of goldfish by using double-label light and electron microscopic
      immunocytochemistry. All labeling to be described was blocked by preabsorption of
      the primary antibodies with antigen. The retina was labeled throughout with all
      three antibodies. However, labeling was densest in the inner plexiform layer for
      Kv1.1, more concentrated in the outer nuclear layer for Kv2.1, and uniform
      throughout for Kv1.2. All ON mixed rod/cone (mb) and cone (cb) bipolar somata and
      the proximal portions of their axons and dendrites were labeled for anti-Kv1.1,
      Kv1.2, and Kv2.1. Labeling of axons rarely extended over the mb axon terminal.
      Only Kv1.2 antibodies labeled mb bipolar cell dendrites in the outer plexiform
      layer. No evidence for Kv1.1, 1.2, or 2.1 antibody labeling of OFF bipolar cells
      was found. Ultrastructurally, Kv1.2-immunoreactivity was associated with the
      plasma membrane of bipolar cell bodies and with dendrites that make narrow-cleft
      junctions with cone terminals (ON-type). Kv immunoreactivity was not found
      associated with presynaptic membranes in the inner plexiform layer and was found
      only rarely with membranes, postsynaptic to an amacrine cell process. Although
      both Shaker and Shab subfamilies include delayed rectifiers, their activation
      properties differ, suggesting differential modulation of K+ conductances in
      bipolar cells based not only on the presence or absence of rod photoreceptor
      input but also whether the bipolar cells are of the ON or OFF type.

PMID- 9623893
TI  - The role of local drug delivery in the management of periodontal diseases: a
      comprehensive review.
AB  - This review article evaluates the role of local drug delivery systems in the
      management of periodontal diseases. The efficacy of several local delivery
      devices (i.e., tetracycline fibers, metronidazole and minocycline gels,
      chlorhexidine chips, and doxycycline polymer) which are either commercially
      available in the United States or abroad, or are currently under consideration
      for Food and Drug Administration (FDA) approval are discussed. The drug delivery
      systems are assessed with regard to their functional characteristics,
      effectiveness as a monotherapy, as compared to scaling and root planing, and
      ability to enhance conventional therapy. Furthermore, controversies associated
      with local delivery are addressed (e.g., induction of bacterial resistant
      strains, the efficacy of systemic versus local drug delivery, and whether local
      drug delivery should function as an alternative or as an adjunct to conventional
      treatment).

PMID- 9623894
TI  - Equivalence and superiority testing in regeneration clinical trials.
AB  - The purpose of this report is to investigate sample size requirements for both
      equivalence and superiority studies investigating products used in regeneration.
      The goal of a superiority clinical trial is to determine if a new therapy is
      superior to an established therapy or placebo. In contrast to superiority trials,
      equivalence trials are used to determine if a new product has similar therapeutic
      properties to an established product. The sample sizes for the two different
      types of clinical trials were based on the following assumptions: an alpha of
      0.05, a power of 0.80, a 2 group parallel arm study, and equal variances and
      sample sizes for both groups. Separate sample size calculations were done for
      both intrabony defects and Class II furcation defects. Sample sizes for the
      equivalence and superiority trials using the same criteria were the same.
      However, criteria for estimating sample sizes for equivalence clinical trials
      require much smaller differences between groups, resulting in much larger sample
      sizes. A criterion of a 20% difference between groups of the total therapeutic
      effect resulted in sample sizes which ranged from 64 to 127 in equivalence
      clinical trials. These samples sizes are much larger than have been generally
      used in clinical trials investigating periodontal regeneration.

PMID- 9623895
TI  - Guided bone regeneration utilizing expanded polytetrafluoroethylene membranes in
      combination with submerged and nonsubmerged dental implants in beagle dogs.
AB  - Treatment of partial and total edentulism with submerged and nonsubmerged dental
      implants which follows the concept of osseointegration has become an accepted
      treatment modality. With compromised implant sites, practitioners have begun to
      combine one-stage implants with established techniques including guided bone
      regeneration. However, the clinical evaluation of this technique is limited.
      Therefore, the purpose of this study was to evaluate osseointegration and bone
      regeneration around nonsubmerged or submerged implants placed directly into
      surgically created osseous defects with or without expanded
      polytetrafluoroethylene (ePTFE) membranes. A total of 24 implants were placed in
      the mandibles of 4 beagle dogs and randomly assigned to 1 of 3 treatment groups.
      In group A, nonsubmerged implants were placed into osseous defects and treated
      with a poncho style ePTFE membrane. These membranes had a hole punched into the
      center and were slipped over the nonsubmerged implants. In group B, nonsubmerged
      implants were placed into osseous defects without an ePTFE membrane. In group C,
      submerged implants were placed into osseous defects and covered with an ePTFE
      membrane. Histometric measurements of each treatment group were made to determine
      percent bone gain or loss along the implant surface. Although a number of
      membrane removals occurred during the healing period, histological analysis
      indicated osseous ingrowth and osseointegration around nonsubmerged and submerged
      implants. An overall comparison of the treatment groups with ANOVA revealed that
      there were no significant differences between treatment groups, P > or = 0.05.
      However, when the data were stratified into sites which retained or lost the
      ePTFE membrane, the percent of bone regeneration was reduced in group A.
      Therefore, it may be recommended that nonsubmerged implants be placed with a
      submerged or "semi-submerged" protocol when utilized in conjunction with ePTFE
      membranes.

PMID- 9623896
TI  - A clinical evaluation of an allograft combined with a bioabsorbable membrane
      versus an alloplast/allograft composite graft combined with a bioabsorbable
      membrane. 100 consecutively treated cases.
AB  - The purpose of this study was to evaluate and compare the clinical effectiveness
      of 2 surgical techniques in treating periodontal defects. Both techniques
      involved tetracycline treatment of a root planed root, grafting the osseous
      defect with a bone graft, and placement of a bioabsorbable membrane. In group A,
      the bone graft was a mix of demineralized freeze-dried allograft, tetracycline,
      and porous hydroxyapatite and in group B, the bone graft was a mix of
      demineralized freeze-dried allograft and tetracycline. There was a statistically
      significant increase in recession (group A, 0.7 mm; group B, 0.6 mm), decreases
      in probing depth (group A, 6.1 mm; group B, 5.6 mm), and gains in attachment
      levels (group A, 5.4 mm; group B, 5.0 mm). There were no statistically
      significant differences between the results for either group. The defects
      associated with furcations and those that were not associated with furcations had
      similar results, except for the percent attachment gain. Smoking and age (> or
      =60 years old) could not be associated with results. Defects with > or =10 mm
      probing depths (PD) had greater PD reductions (group A, 7.7 mm; group B, 7.1) and
      attachment gains (group A, 6.6 mm; group B, 6.4 mm) than the defects with probing
      depths less than 10 mm (probing reduction group A, 4.8 mm; group B, 4.5 mm;
      attachment gain group A, 4.4 mm; group B, 4.0 mm). Both surgical procedures
      improved the clinical situation. However, neither technique seemed to offer a
      statistical advantage over the other. The inclusion of porous hydroxyapatite did
      not improve or diminish the results.

PMID- 9623897
TI  - Working parameters of a magnetostrictive ultrasonic scaler influencing root
      substance removal in vitro.
AB  - This study assessed defect depth and volume resulting from root instrumentation
      using a magnetostrictive ultrasonic scaler with a slim scaling tip (P 12) in
      vitro. Combinations of the following working parameters were analyzed: lateral
      forces of 0.5 N, 1 N, and 2 N; tip angulations of 0 degrees, 45 degrees, and 90
      degrees; power settings of low, medium, and high; and instrumentation time of 10,
      20, 40, and 80 seconds. Defects were quantified using a 3-dimensional optical
      laser scanner. Lateral force had the greatest influence on defect volume compared
      to tip angulation and power setting (beta-weights 0.53+/-0.04, 0.17+/-0.04, and
      0.19+/-0.04, respectively). Lateral force and tip angulation had similar effects
      on defect depth, but both effects were greater compared to power setting (beta
      weights 0.43+/-0.04, 0.49+/-0.04, and 0.19+/-0.04, respectively). The various
      combinations of the assessed working parameters showed synergistic effects
      resulting in a wide range of defect depths (14.1+/-1.7 microm to 410.5+/-51.1
      microm) and volumes (0.0084+/-0.0057 mm3 to 1.3+/-0.079 mm3). Severe root damage
      (defect depth >50 microm) at 40 seconds instrumentation time occurred under most
      combinations of lateral force, angulation, and power settings. The only
      exceptions were combinations of: 1) 0 degrees angulation, 0.5 N and 1 N lateral
      force at any power setting and 2) 45 degrees angulation, 0.5 N lateral force at
      low and medium power setting. The efficacy of the assessed magnetostrictive
      ultrasonic scaler may be adapted to the various clinical needs by adjusting the
      lateral force, tip angulation, and power setting.

PMID- 9623898
TI  - Urinary catecholamine levels and gingivitis in children.
AB  - This study investigated the relationship between gingivitis and emotionally
      stressful states measured by the urinary catecholamines in children. Three
      hundred and fourteen (314) children, boys and girls, aged 6 to 8 years were
      included in the study. Gingivitis was recorded by the gingival bleeding index and
      dental plaque by the plaque control record index. Proximal decayed surfaces,
      faulty restorations, and stainless steel crowns were diagnosed clinically and
      radiographically. Information concerning systemic and socioeconomic factors was
      collected by a questionnaire. A 24-hour urine sample was collected for each
      subject and analyzed by the HPLC technique to assay the catecholamine content.
      The multiple-regression analysis was carried out to test whether gingivitis was
      affected by the studied variables. The 95% probability was used. The results
      showed that epinephrine, norepinephrine, and dopamine did not have a significant
      association with gingival index. Dental plaque and proximal decayed surfaces
      significantly affected gingivitis. Of the socioeconomic factors, mother's
      education had a significant association with gingivitis when all factors were
      included in the analysis. The data suggest that emotionally stressful states may
      not increase the probability of developing gingivitis in children of this age.

PMID- 9623899
TI  - The effect of root surface demineralization on bone morphogenetic protein-2
      induced healing of rat periodontal fenestration defects.
AB  - The purpose of this study was to investigate the effect of acid conditioning of
      root surfaces during recombinant human bone morphogenetic protein-2 (rhBMP-2)
      induced periodontal regeneration in vivo. The buccal aspect of molar roots were
      denuded of their periodontal ligament through a bony window created in the
      mandible of 34 Wistar rats under general anesthesia. Three groups of 11 or 12
      animals received either 10 microL of 50 g/mL rhBMP-2 in a collagen gel over the
      surgical defect (BMP) or 10 microL of collagen gel only (COL) or were left
      untreated (UN). Each of the 3 groups were further subdivided into those that
      received prior root acid conditioning with 35% phosphoric acid gel and those
      without acid conditioning. Animals were sacrificed 10 days after surgery and the
      tissues processed for histological examination. The BMP groups with and without
      acid conditioning developed significantly more bone over the second molar (3.89+/
      0.86% and 7.62+/-0.93%, respectively; mean+/-SE), compared with the respective
      COL (1.24+/-0.26% and 2.77+/-0.52%) and UN groups (1.34+/-0.35% and 3.69+/-0.37%)
      (P <0.05). Furthermore, significantly more bone was found in the BMP non-acid
      conditioned group compared with all other groups (P <0.05). Acid conditioning
      promoted significantly more ankylosis (50%) compared with non-acid conditioning
      (6.3%) (P=0.007). New cementum formation was greatest in the BMP acid conditioned
      group (628.4+/-253.8 microm2) and lowest in the non-acid conditioned UN group
      (207.6+/-36.4 microm2) (P <0.05). This is the first known report evaluating the
      effects of root acid conditioning after a single application of rhBMP-2 in vivo.
      Results suggest that root conditioning agents operating at low pH administered
      into the periodontal wound impairs early BMP-induced osteogenesis while
      simultaneously promoting BMP-induced cementogenesis.

PMID- 9623900
TI  - Periodontal status and serum antibody responses to oral microorganisms in
      Sjogren's syndrome.
AB  - Sjogren's syndrome is an autoimmune disease characterized by keratoconjunctivitis
      sicca and xerostomia. Rapid bacterial plaque accumulation occurs in Sjogren's
      syndrome patients due to decreases in salivary flow rate. The purpose of this
      study was to evaluate the periodontal status of patients with Sjogren's syndrome
      and evaluate serum antibody responses to selected oral microorganisms, including
      major periodontopathogens, compared to healthy controls. Seventeen Sjogren's
      syndrome patients and 14 healthy subjects were included in the study. Plaque
      (PL), sulcular bleeding (SBI), periodontal index scores (PI), probing depths
      (PD), and total number of teeth were recorded. An ELISA was used to determine the
      serum IgG antibody level to a panel of 13 oral microorganisms. Significantly
      higher PL, SBI, PD, and PI scores, as well as an increased number of lost teeth
      were observed in patients with Sjogren's syndrome compared to healthy subjects (P
      <0.0001). Antibody levels to Streptococcus oralis were significantly lower in
      Sjogren's syndrome patients than controls (P <0.0002). These patients exhibited
      significantly elevated antibody levels to Actinobacillus actinomycetemcomitans
      and Porphyromonas gingivalis compared to controls (P <0.006 to 0.0004). Our
      findings indicate that Sjogren's syndrome patients have established periodontal
      disease and serum antibody responses to oral microorganisms previously identified
      as periodontopathogens in systemically healthy subjects. These results suggest
      that Sjogren's syndrome may affect bacterial colonization in plaque and
      contribute to increased periodontal disease in this compromised population.

PMID- 9623901
TI  - Retention, antimicrobial activity, and clinical outcomes following use of a
      bioerodible tetracycline gel in moderate-to-deep periodontal pockets.
AB  - This randomized, examiner masked, split mouth study evaluated a new model to test
      periodontal therapy involving a novel bioerodible copolymer gel containing
      tetracycline hydrochloride. Responses to the tetracycline gel and untreated
      control were compared for product tolerance and 3 different measures of
      effectiveness (drug retention, changes in microbial levels, and clinical status).
      The test gel was administered by syringe into the periodontal pockets of 18
      systemically healthy adult volunteers, each of whom presented with 3 or more
      sites with 6 mm probing depths. Gingival crevicular fluid samples were used to
      monitor daily drug levels over 7 days, while clinical responses were assessed at
      day 30. Overall, the test gel was well-tolerated by all patients. For the 3
      effectiveness measures, tetracycline was released throughout the observation
      period and mean levels exceeded 100 microg/mL over 6 days, statistically
      significant reductions in selected periodontal pathogens were evident at day 7
      but not at day 30, and mean probing depth reductions at test sites were 1.12 mm
      at 30 days versus 0.36 mm at untreated control sites (P=0.012). The safety
      profile, longer-term drug retention, antimicrobial activity, and clinical
      response in this Phase I study suggest that this tetracycline-containing
      copolymer gel platform may represent a safe and effective bioerodible therapy for
      periodontitis. The experimental model also shows merit for early phase clinical
      testing of novel therapeutic agents.

PMID- 9623902
TI  - Three-dimensional alveolar bone morphology analysis using computed tomography.
AB  - The purpose of the present study was to determine whether the use of 3
      dimensional computed tomography (3DCT) is an effective method of imaging bone
      defect morphology caused by periodontal disease. A total of 186 sites from 9
      patients were examined. Periodontal parameters were recorded after initial
      therapy. For the evaluation of bone resorption and root morphology, computed
      tomography (CT) scanning was performed and then CT images were reconstructed for
      3-dimensional evaluation. Immediately prior to the surgery, bone sounding
      measurements were done under local anesthesia. The denuded bone measurement
      during periodontal surgery represented the true bone level. To compare the bone
      level obtained from 3DCT images with the true bone level, the examiner, without
      being informed of the patient's condition, traced the cemento-enamel junction
      (CEJ) and apical extent of the bone levels on the images of 3DCT, and measured
      the vertical distance between the CEJ and bone. The mean difference between 3DCT
      and the true bone level was 0.41+/-2.53 mm (mean+/-SD). The correlation between
      them showed a highly significant linear regression (R=0.75). However, the mean
      difference between the bone sounding level and the true bone level was 0.22+/
      1.49 mm (R=0.91). Thus, bone sounding was slightly more accurate than 3DCT, but
      there was no significant difference between these two assessments (P >0.05). The
      results of present study indicate that 3DCT has the potential to allow precise
      assessment of bone defect caused by periodontal disease.

PMID- 9623903
TI  - Radiographic and clinical responses to periodontal therapy.
AB  - Mechanical periodontal therapy is widely used for a variety of periodontal
      conditions. While the clinical efficacy of this treatment has been validated, the
      radiographic response has not been studied in depth. The purpose of the present
      study was to examine the clinical and radiographic response to mechanical
      periodontal therapy, and assess the factors associated with these changes. One
      hundred and eight patients, with established periodontitis, received oral hygiene
      instruction and mechanical periodontal therapy for a period of 4 to 5 weeks.
      Scheduled maintenance visits were performed at 3, 6, 9, and 15 months. Probing
      depth (PD) and attachment level (AL) measurements were performed at baseline, and
      at 3 and 15 months. Intraoral radiographs were taken at baseline and 12 to 15
      months postsurgery using a Rinn alignment system. Alveolar crestal height (ACH)
      measurements were performed on a pair of digitized images of the previously taken
      radiographs. An overall mean of patients' changes for PD, AL, and ACH was
      initially computed. Active sites (gainers and losers) were determined using a
      threshold method, and expressed as patient's percentage of active sites (number
      of active sites of the total sites measured in each patient). Mean overall
      probing reduction and AL gain was 0.5 mm and 0.44 mm, respectively. Of all sites
      measured, 16.6% exhibited AL gain, while only 6.2% of all sites exhibited AL
      loss. Mean overall change in ACH was -0.07 mm, of which 11.8% of all sites
      exhibited ACH gain, while 15.1% exhibited loss beyond the threshold. Non-smokers
      presented no change in bone loss, while smokers continued to lose bone at an
      annual rate of 0.17 mm, despite treatment (P <0.005). Likewise, the average
      percent of sites per patients showing attachment gain beyond the threshold were
      much greater in non-smokers (13.9%) compared to 9.0% in smokers (P <0.01). Mean
      probing reduction was 50% greater among non-smokers (0.6 mm) when compared to
      smokers (0.4 mm), which was also statistically significant (P <0.05). A positive
      and significant correlation was established between the percentage of sites with
      AL gain and sites with ACH gain (Rho =0.40; P=0.0001). It is suggested that
      monitoring sites for AL and ACH gain expressed as changes beyond a selective
      threshold is an important outcome variable in treatment studies.

PMID- 9623904
TI  - Repair of a root resorption lesion. A case report.
AB  - An extensive root surface lesion that presented both supra- and subgingival
      components was successfully treated with the use of glass ionomer cement to
      restore the lesion, and facilitate subsequent endodontic therapy and restoration.
      A coronally-positioned flap covered the repaired/restored lesion, approximately 6
      mm x 10 mm in dimension. At 6 months following placement of the restoration, all
      but 1 mm of the restoration appeared covered, with probing depths <3 mm and no
      clinical signs of inflammation. Glass ionomer cement appears to be a viable,
      biocompatible material to restore subgingival root surface lesions.

PMID- 9623905
TI  - A combined approach for treatment of developmental groove associated periodontal
      defect. A case report.
AB  - Developmental grooves are not rare and often appear on maxillary lateral
      incisors. This may represent a challenge and sometimes tooth extraction is
      inevitable. This case report describes a combined technique of regenerative and
      antimicrobial/root conditioning used to treat a maxillary lateral incisor in a 32
      year-old woman. Tooth #10 presented a periodontal probing depth of 8 mm below the
      cingulum, associated with a developmental groove. The tooth was vital. After
      initial preparation, a palatal mini-flap was raised, granulation tissue was
      eliminated by means of ultrasonic bactericidal curettage and radicoloplasty
      performed. The surface was then treated for 3 minutes with tetracycline-HCl
      solution (100mg/ml), and the defect filled with sterile, medical grade, calcium
      sulfate. Clinical measurements were retaken at 6, 12, and 18 months. The results
      indicated a reduction of probing depth to 2 mm, reestablishment of the lamina
      dura, and radiographical evidence of bone growth. This combined treatment allowed
      the tooth to be saved, the palatal surgical approach did not alter the esthetics
      of the area, and its simplicity is recommended.

PMID- 9623906
TI  - Equivalence, superiority, and negative clinical trials.

PMID- 9623907
TI  - Seven retinal specializations in the tubular eye of the deep-sea pearleye,
      Scopelarchus michaelsarsi: a case study in visual optimization.
AB  - The deep-sea pearleye, Scopelarchus michaelsarsi (Scopelarchidae) is a
      mesopelagic teleost with asymmetric or tubular eyes. The main retina subtends a
      large dorsal binocular field, while the accessory retina subtends a restricted
      monocular field of lateral visual space. Ocular specializations to increase the
      lateral visual field include an oblique pupil and a corneal lens pad. A detailed
      morphological and topographic study of the photoreceptors and retinal ganglion
      cells reveals seven specializations: a centronasal region of the main retina with
      ungrouped rod-like photoreceptors overlying a retinal tapetum; a region of high
      ganglion cell density (area centralis of 56.1 x 10(3) cells per mm2) in the
      centrolateral region of the main retina; a centrotemporal region of the main
      retina with grouped rod-like photoreceptors; a region (area giganto cellularis)
      of large (32.2+/-5.6 microm2), alpha-like ganglion cells arranged in a regular
      array (nearest neighbour distance 53.5+/-9.3 microm with a conformity ratio of
      5.8) in the temporal main retina; an accessory retina with grouped rod-like
      photoreceptors; a nasotemporal band of a mixture of rod- and cone-like
      photoreceptors restricted to the ventral accessory retina; and a retinal
      diverticulum comprised of a ventral region of differentiated accessory retina
      located medial to the optic nerve head. Retrograde labelling from the optic nerve
      with DiI shows that approximately 14% of the cells in the ganglion cell layer of
      the main retina are displaced amacrine cells at 1.5 mm eccentricity.
      Cryosectioning of the tubular eye confirms Matthiessen's ratio (2.59), and
      calculations of the spatial resolving power suggests that the function of the
      area centralis (7.4 cycles per degree/8.1 minutes of arc) and the cohort of
      temporal alpha-like ganglion cells (0.85 cycles per degree/70.6 minutes of arc)
      in the main retina may be different. Low summation ratios in these various
      retinal zones suggests that each zone may mediate distinct visual tasks in a
      certain region of the visual field by optimizing sensitivity and/or resolving
      power.

PMID- 9623908
TI  - Sonic/vocal motor pathways in catfishes: comparisons with other teleosts.
AB  - Among teleost fishes, representatives of several distantly related groups have
      sound-producing (sonic/vocal) muscles associated with the swimbladder or pectoral
      girdle/fin. Here, the diversity of vocal organs and central motor pathways in
      four families of catfish, order Siluriformes, is compared to that in families
      from two distantly related orders, the Scorpaeniformes and Batrachoidiformes.
      Several catfish families have two sonic mechanisms--a swimbladder vibration
      established by 'drumming muscles' that differ in origin and insertion between
      families, and a pectoral spine stridulatory apparatus. In ariids, mochokids and
      doradids, sonic swimbladder muscles originate at various cranial or postcranial
      elements and insert onto an 'elastic spring' that vibrates the swimbladder, while
      in pimelodids the muscles insert ventrally at the swimbladder. Sonic motoneurons
      are located along the midline, ventral to the fourth ventricle/central canal in
      doradids and mochokids but lateral to the medial longitudinal fasciculus in
      ariids; pimelodids have motoneurons in both locations. The axonal trajectory for
      the lateral motoneurons in pimelodids and ariids implies that they are a
      migrated, midline population of sonic motoneurons. Pectoral spine-associated
      motoneurons are located in the ventral motor column. Unlike catfishes, a
      diversity of sonic mechanisms in Scorpaeniformes is not associated with different
      positions for sonic motoneurons. Cottids (sculpin) lack a swimbladder but have
      sonic muscles that originate at the occipital cranium and insert at the pectoral
      girdle; sonic motoneurons are located within the ventral motor column. Some
      triglids have intrinsic swimbladder muscles, although ontogenetic data indicate a
      transient association with the pectoral girdle; sonic motoneurons are in the same
      location as in cottids. Among Batrachoidiformes, all known representatives have
      intrinsic swimbladder muscles that are never associated with the pectoral girdle
      and are innervated by midline sonic motoneurons. The results suggest two patterns
      of organization for sound-producing systems in teleost fishes: pectoral
      fin/girdle-associated muscles are innervated by sonic motoneurons positioned
      within the ventral motor column, adjacent to the ventral fasciculus; non-pectoral
      associated muscles are innervated by sonic motoneurons located on or close to the
      midline, adjacent to the medial longitudinal fasciculus.

PMID- 9623909
TI  - A comparison of the linear tuning properties of two classes of axons in the
      bullfrog lagena.
AB  - Various vertebrate inner-ear end organs appear to have switched their sensory
      function between equilibrium sensing and acoustic sensing over the courses of
      various lines of evolution. It is possible that all that is required to make this
      transition is to provide an end organ with access to the appropriate stimulus
      mode and frequency range. If, as we believe, however, the adaptive advantage of
      an acoustic sensory system lies in its ability to sort the total acoustic input
      into components that correspond to individual acoustic sources, and the adaptive
      advantage of an equilibrium sensory system lies in its ability to compute the
      total orientation and motion of the head without regard to the individual sources
      contributing to that orientation and motion, then it is easy to argue that the
      differences between acoustic and equilibrium sensors should be more profound than
      simply access to the appropriate stimuli. Effective signal-sorting requires high
      resolution in both time and frequency; to achieve this resolution, a peripheral
      tuning structure must be one of high dynamic order (i.e., constructed from
      multiple independent energy storage elements). If the peripheral tuning structure
      simply converts head acceleration to head displacement, velocity, or jerk (i.e.,
      provides one or two steps of integration or differentiation with respect to time,
      where one energy storage element per step is required), then high dynamic order
      is inappropriate. Because the bullfrog lagena possesses both acoustic and
      equilibrium sensitive regions, it is especially suited for comparing these two
      sensor types and addressing the question of dynamic order of tuning. In this
      paper we report observations of the linear tuning properties of bullfrog lagenar
      primary afferent nerve fibers obtained by stimulating the lagena with random,
      dorsoventral micromotion over the frequency range from 10 Hz to 1.0 kHz. Tuning
      curves obtained by reverse correlation analysis and discrete Fourier
      transformation were used to estimate the dynamic order of each fiber's associated
      peripheral tuning structure. We found two classes of lagenar afferent axons-
      those with lowpass amplitude tuning characteristics (44 units) and those with
      bandpass amplitude tuning characteristics (73 units). Lowpass units were found to
      originate at the equilibrium region of the macula, and they exhibited low dynamic
      order--summed low- and high-frequency slopes (absolute values) ranged from 10
      dB/decade to 64 dB/decade, implying dynamic orders of less than one to three (the
      modal value was equal to one). Bandpass units were found to originate at the
      acoustic region of the macula, and they exhibited higher dynamic order than
      lowpass units--summed low- and high-frequency slopes (absolute values) ranged
      from 53 dB/decade to 185 dB/decade, implying dynamic orders of three to nine (the
      modal value was equal to five). It appears that while lagenar equilibrium and
      acoustic sensors both possess access to signals in the acoustic frequency range,
      lagenar acoustic sensors are tuned by means of peripheral structures with
      markedly greater dynamic order and consequently markedly greater physical
      complexity. These results suggest that steep-sloped (high-dynamic-order) tuning
      properties reflect special adaptations in acoustic sensors not found in
      equilibrium sensors, and that any evolutionary transition between the two sensor
      types must have involved profound structural changes.

PMID- 9623910
TI  - A new approach to AIDS research and prevention: the use of gene-mutated HIV-1/SIV
      chimeric viruses for anti-HIV-1 live-attenuated vaccines.
AB  - The lack of a suitable animal model is a major obstacle to developing anti-HIV-1
      vaccines. We successfully generated an SIVmac/HIV-1 chimeric virus (SHIV)
      (designated as NM-3rN) that contains the HIV-1 env gene and is infectious to
      macaque monkeys. Challenging the vaccinated macaque monkeys with NM-3rN, we
      developed an evaluation system for anti-HIV-1 Env-targeted vaccines. For the
      purpose of making the vaccine, a series of gene-mutated SHIVs were constructed.
      The monkeys vaccinated with these SHIVs had long-term anti-virus immunities
      without manifesting the disease, and became resistant to a challenge inoculation
      with NM-3rN. The sera from a monkey showed that, after the vaccination, the
      neutralizing antibodies not only against the parental HIV-1 but also against an
      antigenically different HIV-1 were raised. In vivo experiments confirmed that the
      vaccinated monkeys were protected from the challenge inoculum of an antigenically
      different SHIV-MN. Vaccination of monkeys with the attenuated SHIVs showed that
      further gene-deletion of the SHIV resulted in less immunogenicity. Nevertheless,
      the attenuated SHIVs had a vaccine effect against the challenge inoculation. In
      addition to specific immunities including neutralizing antibodies and cytotoxic T
      cells, a more complicated immune mechanism induced by live vaccine appears to
      play a role in this protection. Our data suggest that the live vaccine can induce
      strong and wide-range immunity against HIV-1. These SHIVs should contribute to
      understanding the pathogenicity of AIDS and to the development of future anti-HIV
      1 live vaccines for humans.

PMID- 9623911
TI  - Molecular characterization of low-molecular-weight component protein, Flp, in
      Actinobacillus actinomycetemcomitans fimbriae.
AB  - Fimbriae preparation from Actinobacillus actinomycetemcomitans was found to
      contain an abundant low-molecular-weight protein (termed Flp) with an apparent
      molecular mass of approximately 6.5 kDa, in addition to a small amount of 54-kDa
      protein. Immunogold electron microscopy localized the Flp protein at the
      bacterial fimbriae but not at the cell surface. The DNA fragment including the
      flp gene was cloned from A. actinomycetemcomitans 304-a and its nucleotide
      sequence was determined. An open reading frame of the flp gene was composed of
      225 bp encoding a protein of 75 amino acids. Comparison of the translated amino
      acid sequence with the sequence of native Flp determined by Edman degradation
      indicated that the N-terminal part of 26 amino acids is leader peptide. The N
      terminal sequence of mature Flp exhibited some similarity to type-IV pilin.
      Furthermore, the processing site of premature Flp is also similar to that of type
      IV prepilin, and a gene encoding a protein homologous to type-IV prepilin-like
      protein leader peptidase was found downstream of the flp gene. These findings
      indicate that Flp is the major component protein of A. actinomycetemcomitans
      fimbriae.

PMID- 9623912
TI  - Epidemiologic study of Shigella sonnei from sequential outbreaks and sporadic
      cases using different typing techniques.
AB  - We noted that eight outbreaks of Shigella sonnei from an unknown source occurred
      sequentially in Aichi Prefecture, Japan, between October 1992-June 1993. For
      comparative purposes we analyzed 53 outbreak-related isolates of Shigella sonnei
      using different subtyping methods and studied the epidemiology of the outbreaks.
      It appeared from our study that DNA-based techniques such as plasmid typing and
      pulsed-field gel electrophoresis (PFGE) were more useful tools for subtyping
      Shigella sonnei than colicin typing and the antimicrobial susceptibility test.
      Moreover, according to PFGE analysis, four genetically related isolates of
      Shigella sonnei were responsible for the eight sequential outbreaks. To further
      investigate the epidemiology of outbreaks, 58 sporadic isolates of Shigella
      sonnei from overseas travelers with shigellosis during the same period were also
      examined. We found that some sporadic isolates from travelers in Asia were
      genetically related to those of the outbreak-related isolates, indicating that
      genetically related isolates prevailed in Asia during this period, probably
      because of the extensive movement of people or food.

PMID- 9623913
TI  - Studies of Escherichia coli cultured on Rainbow Agar O157 with particular
      reference to enterohaemorrhagic Escherichia coli (EHEC).
AB  - Rainbow Agar O157 is designed for the rapid isolation and identification of
      enterohaemorrhagic Escherichia coli (EHEC), particularly O157, characterised by
      black colonies. Five-hundred-eighty-five E. coli strains, including O157, O111
      and O113 serogroups from many sources were examined on Rainbow Agar O157. EHEC
      O157 could readily be isolated and recognized uniquely by typical black colonies.
      Some other EHEC also stand out as blue-black, whereas O113 and some other EHEC
      strains were mauve, red or pink and indistinguishable from SLT-negative strains
      of E. coli.

PMID- 9623914
TI  - Multiplication of Legionella pneumophila in HeLa cells in the presence of
      cytoskeleton and metabolic inhibitors.
AB  - A study has been carried out on the action of cytoskeleton and metabolic
      inhibitors on intracellular multiplication in HeLa cells of a virulent strain of
      Legionella pneumophila serogroup 6. The effects of the substances were separately
      tested on both penetration and intracellular multiplication of L. pneumophila.
      Only cytochalasin A and 2-deoxy-D-glucose (2dG) affected bacterial
      internalisation, whereas intracellular multiplication was inhibited by
      cytochalasins A, B, C, D and J (D being the most active) and by 2dG with a dose
      response effect. The action of 2dG was counteracted by 50 mM glucose. Experiments
      carried out with cytochalasin D and a rhodamine-phalloidin conjugate showed the
      involvement of cytoskeletal elements in intracellular multiplication of
      Legionella; compounds acting on microtubules had no effect.

PMID- 9623915
TI  - Diagnostic value of the Amplicor PCR assay for initial diagnosis and assessment
      of treatment response for pulmonary tuberculosis.
AB  - We evaluated the Amplicor PCR assay as an initial diagnostic tool on the basis of
      clinical diagnosis, and assessed this assay as a follow-up test for patients with
      pulmonary tuberculosis during chemotherapy. Of the 208 specimens from 155
      patients who were bacteriologically and/or clinically diagnosed with active
      tuberculosis before chemotherapy, 144 were Amplicor PCR-positive (sensitivity,
      69.2%), which was equal to the results of culturing. Among 89 specimens which
      showed positive results by smear and culturing, the Amplicor PCR assay detected
      87 (97.8%), whereas among 55 specimens which showed smear-negative but culture
      positive results, the Amplicor PCR assay detected 46 (83.6 %)(P= 0.003). No false
      positive results were found in the two systems (specificity, 100%, 120/120). The
      Amplicor PCR assay was also evaluated as a follow-up test using 926 specimens
      from 207 patients receiving active tuberculosis chemotherapy. Among 433 specimens
      which showed Amplicor-PCR positive, 222 (51.3%) were culture-negative. On the
      other hand, among 233 culture-positive specimens, only 12 (5.2%) were Amplicor
      PCR-negative. Therefore, this assay is useful for the rapid diagnosis of
      tuberculosis. The duration of Amplicor PCR-positive after culture-negative
      conversion was significantly associated with the presence of cavitary lesion,
      smear-positive specimens before treatment, and smear-positive specimens with
      negative cultures during chemotherapy.

PMID- 9623916
TI  - The 21-kDa polypeptide (VAP21) in the rabies virion is a CD99-related host cell
      protein.
AB  - In our monoclonal antibody (MAb) stocks prepared against the BHK-21 cell
      antigens, two (#11875 and 28276) recognized a 21-kDa polypeptide (referred to as
      VAP21) which is efficiently incorporated into the rabies virion. By using these
      MAbs, we isolated the cDNA clones that encoded a polypeptide of 144 amino acids
      from our BHK-21 cell cDNA library. Based on the following evidence, the cDNA was
      assumed to encode a full-length sequence of VAP21 antigen: i) expression of the
      cDNA in animal cells resulted in the production of a polypeptide recognized by
      the two MAbs, and its electrophoretic mobility was the same as that of authentic
      VAP21 antigen; and ii) immunization with the products from the cDNA-transformed
      E. coli cells raised specific antibodies in rabbits that recognized a 21-kDa
      polypeptide in the virion. From the deduced amino acid sequence, it is suggested
      that the VAP21 antigen has a molecular structure of type-I transmembrane protein
      containing characteristic proline-rich and glycine-rich regions in its
      ectodomain. Homology searches resulted in finding homologous sequences (totally
      about 40% homology) in the human MIC2 gene product (CD99; 32-kDa) of T
      lymphocytes. These results suggest that the VAP21 antigen in the rabies virion is
      a cellular CD99-related transmembrane protein.

PMID- 9623917
TI  - Relation between reactivity to the NS-4 region peptides of hepatitis C virus
      (HCV) and clinical features among patients infected with HCV genotype 1b.
AB  - Nearly all patients infected with hepatitis C virus (HCV) genotype 1b have
      reactivity to the core (c22-3) or non-structural (NS)-3 region (c33c) protein in
      a second-generation recombinant immunoblot assay (RIBA-2). However, reactivities
      to the NS-4 region antigens (5-1-1, c100-3) vary among patients. To clarify
      whether differences in serological reactivities to the NS-4 antigens are
      associated with the clinical features or response to interferon (IFN) therapy of
      patients infected with hepatitis C virus (HCV) genotype 1b, we clinically
      investigated 115 such patients. Positive reactions to 5-1-1 and c100-3 were seen
      in 75.7 and 79.1%, respectively, of the patients. There were no differences
      between the patients with and those without antibodies to NS-4 region antigens (5
      1-1, c100-3) with regard to age, duration of HCV infection, severity of liver
      disease and virus load. Fifty-one of the patients were treated with recombinant
      IFN-alpha, and 17 of the 51 patients showed sustained response to the therapy.
      The sustained response was more frequently seen in the patients positive for
      antibodies to both 5-1-1 and c100-3 as compared with those negative for either or
      both antibodies (41.0% vs. 8.3%, P<0.05).

PMID- 9623918
TI  - Detection of HIV-Gag p24-specific antibodies in sera and saliva of HIV-1-infected
      adults and in sera of infants born to HIV-1-infected mothers.
AB  - Secretory immunoglobulin A (IgA) is known to play an important role in the
      mucosal defense against a variety of pathogens. Although the role of IgA
      antibodies during sexual transmission of HIV is not clear, HIV-specific IgA
      antibodies have been detected in various mucosal secretions of HIV-infected
      individuals. Using a monoclonal antibody against human IgA, we established an
      ELISA system to detect anti-HIV p24 IgA antibodies in sera and saliva. We have
      analyzed the levels of anti-HIV p24 IgG and IgA antibodies in sera and saliva of
      107 and 119 adults, respectively, with HIV infection at different clinical
      stages, and in the sera of 13 infants born to HIV-infected mothers. The level of
      anti-HIV p24 IgA antibodies was lower in sera and higher in saliva as compared to
      that of anti-HIV p24 IgG antibodies. Where the percentage of HIV-specific serum
      antibody-positive cases decreased with disease progression, that of saliva
      antibody-positive cases increased in AIDS patients. Among the 13 infants born to
      HIV-infected mothers, 7 infants were HIV-p24-specific serum IgA positive. These
      sera were negative for anti-HIV p24 secretory IgA, suggesting that some infants
      develop their own immune responses against HIV infection. Thus, the detection of
      HIV-specific IgA antibodies, especially in saliva, could be a simple and reliable
      test for the diagnosis of HIV infection.

PMID- 9623919
TI  - Human immunodeficiency virus type 1 (HIV-1) infection and transcytosis activity
      of a HIV-1 susceptible clone from HeLa cell.
AB  - In order to clarify the transmission process of human immunodeficiency virus type
      1 (HIV-1) through the epithelial cell barrier, HeLa cells susceptible and non
      susceptible to HIV-1 were cloned and designated as P6 HeLa and N7 HeLa cells,
      respectively. P6 HeLa cells could be infected with the LAI strain of HIV-1 and
      mediated HIV-1 transcytosis. In contrast, N7 HeLa cells exhibited neither HIV-1
      infection nor transcytosis. CD4 and galactosylceramide as the receptors for HIV-1
      were not detected on P6 HeLa cells, although an anti-CD4 monoclonal antibody
      (mAb) blocked HIV-1 infection. Since HIV-1-infected P6 HeLa cells exhibited no
      fusion and survived, we speculated that the P6 HeLa cells expressed molecules
      other than CD4 which facilitated HIV-1 infection. Two mAbs (A-14 ITK and C57 a9
      9) which inhibited the HIV-1 infection of P6 HeLa cells were generated. Each mAb
      recognized distinct molecule(s) as shown by Western blotting. Transcytosis by the
      P6 HeLa cells was inhibited by C57 a9-9 but not by A-14 ITK or anti-CD4 mAb. Both
      infection and transcytosis may be responsible for HIV-1 transmission through
      epithelial cells in a complex manner. Although infection and transcytosis
      occurred via different mechanisms, the molecule(s) recognized by C57 a9-9 mAb may
      be associated with both processes.

PMID- 9623920
TI  - Inhibitory effect of bacterial attachment on candidal growth due to adherence
      with mannose-sensitive pili.
AB  - A bacterial strain with affinity to Candida albicans was successfully obtained
      from a natural environment. An uncovered Petri dish containing a suspension of
      heat-killed C. albicans cells was allowed to stand in a laboratory for several
      days. Some bacteria which had adhered to the candidal cells were tested for their
      ability to agglutinate the cells. A bacterial strain, designated later as CAB-1,
      was found to agglutinate candidal cells through bridging by mannose-sensitive
      pili. CAB-1 showed similar bacteriological characteristics to those of
      Citrobacter freundii by ID test. The adherence of CAB-1 to candidal cell was
      precisely presented by scanning electron microscopy. The inhibitory effect of CAB
      1 attachment to candidal cells on the growth of Candida was also preliminarily
      confirmed.

PMID- 9623921
TI  - Systemic dissemination by intrarectal infection with Listeria monocytogenes in
      mice.
AB  - Orally ingested Listeria monocytogenes is known to penetrate into Peyer's patches
      (PP) and translocate to the spleen and liver. Herein, extraintestinal
      dissemination of the bacterium independent of PP was investigated. Dissemination
      of Listeriae to the spleen and liver was observed in intrarectally infected mice
      as well as in intragastrically infected animals in spite that no Listeriae were
      detected in the small intestines of mice infected intrarectally. Decreased
      numbers of intestinal intraepithelial lymphocytes (iIEL) and increased numbers of
      lymphocytes in the contents of the small and large intestines were observed after
      intragastric infection and in the large intestine after intrarectal infection,
      giving the assumption that the leakage of iIEL caused by injury of epithelial
      layers in intestines might occur during infection. These results suggest that L.
      monocytogenes might be able to disseminate through small and large intestines in
      part by a PP-independent mechanism.

PMID- 9623922
TI  - Evidence for a dual strategy in the expression of cauliflower mosaic virus open
      reading frames I and IV.
AB  - Studies have indicated that cauliflower mosaic virus (CaMV) gene expression is
      mediated by the translation of polycistronic 35S pregenomic RNA, but the
      involvement of some minor subgenomic RNA species is also suspected. We examined
      the involvement of the 35S promoter in the expression of CaMV open reading frames
      (ORFs) I and IV using both 35S RNA-driven and promoter-less ORF I- and ORF IV
      beta-glucuronidase (GUS) fusion constructs. In addition to the 35S promoter
      dependent expression of both ORF I- and IV-GUS fusions, we detected the 35S
      promoter-independent expression of both fusion genes via subgenomic mRNAs, which
      were detected by Northern blotting in the protoplasts transfected with the 35S
      promoter-driven constructs as well as in those transfected with the promoter-less
      constructs. These results suggest the involvement of subgenomic RNAs in the
      expression of CaMV ORFs I and IV, and the operation of a dual strategy in the
      expression of two viral genes.

PMID- 9623923
TI  - Pathogenicity of a mutant friend spleen focus-forming virus encoding an Env-like
      membrane glycoprotein (gp55) with substitution by a xenotropic murine leukemia
      virus Env gp70 sequence.
AB  - Friend spleen focus-forming virus (F-SFFV) is a replication-defective acutely
      leukemogenic mouse retrovirus and encodes an envelope protein (Env)-like membrane
      glycoprotein (gp55) in its defective env gene, which is responsible for the early
      stage of the viral leukemogenesis. Gp55 is a modified Env protein and contains a
      polytropic mink cell focus-inducing (MCF) murine leukemia virus (MuLV) Env gp70
      derived sequence in its amino-terminal region. To evaluate the possibility that
      the presumed binding of gp55 to an MCF MuLV receptor protein has some role in
      leukemogenesis, we examined the biological activities of a mutant gp55 (XE gp55),
      which has a xenotropic MuLV Env gp70 amino-terminal region. XE gp55 displayed
      almost the same biological activities as the wild-type gp55, excluding the above
      possibility.

PMID- 9623924
TI  - Do we need population monitoring laboratories to evaluate community-based
      prevention of cardiovascular disease in developing countries?

PMID- 9623925
TI  - There are no shortcuts to finding out what works--population laboratories are
      essential tools.

PMID- 9623926
TI  - A comparison of oral fluid and serum for the detection of rubella-specific
      antibodies in a community study in Addis Ababa, Ethiopia.
AB  - OBJECTIVE: To assess the utility of oral fluid compared with serum for the
      determination of age-prevalence of rubella-specific antibodies in an urban
      African community setting. METHOD: Paired serum and oral fluid samples were
      collected from 439 individuals aged 0-49 years in Addis Ababa, Ethiopia, as part
      of a larger seroepidemiological survey in 1994. Oral fluid was sampled using a
      simple sponge device that was well accepted by subjects of all ages; venous blood
      was collected by Vacutainer system. We measured rubella-specific antibodies in
      serum by the Radial Haemolysis (RH) test, supported by two confirmatory assays,
      and in oral fluid by IgG antibody-capture radioimmunoassay (GACRIA). RESULTS:
      Sensitivity and specificity of oral fluid results compared to serum were 89% and
      76%, respectively. Sensitivity declined from 96% in age group 0-19 years to 90%
      in age group 20-29 and 78% in age group 30-49. Specificity was 86% in 0-9 year
      olds contrasting with 61% in older groups (10-49 years). The positive predictive
      value of an oral fluid sample was high in all age groups (range 92-100%), while
      the negative predictive value declined from > or =80% in those aged <10 years to
      <10% in those aged > or =30 years. Serum confirmatory tests suggested a
      proportion of false serum RH negatives, increasing with age, indicating a need to
      standardize serum as well as oral fluid tests. CONCLUSION: In the community
      setting of a developing country, oral fluid surveys could be useful to estimate
      age-prevalence of rubella immunity and identify rubella-susceptible children for
      follow-up. Further work is required to simplify assays and sample processing,
      improve assay sensitivity and estimate assay specificity more precisely, and
      compare and standardise collection methods suitable for surveillance of a variety
      of childhood viral infections.

PMID- 9623927
TI  - Respiratory syncytial virus infection in tropical and developing countries.
AB  - Little is known about the epidemiology of respiratory syncytial virus (RSV)
      infection in tropical and developing countries; the data currently available have
      been reviewed. In most studies, RSV was found to be the predominant viral cause
      of acute lower respiratory tract infections (ALRI) in childhood, being
      responsible for 27-96% of hospitalised cases (mean 65%) in which a virus was
      found. RSV infection is seasonal in most countries; outbreaks occur most
      frequently in the cold season in areas with temperate and Mediterranean climates
      and in the wet season in tropical countries with seasonal rainfall. The situation
      on islands and in areas of the inner tropics with perennial high rainfall is less
      clear-cut. The age group mainly affected by RSV in developing countries is
      children under 6 months of age (mean 39% of hospital patients with RSV). RSV-ALRI
      is slightly more common in boys than in girls. Very little information is
      available about the mortality of children infected with RSV, the frequency of
      bacterial co-infection, or the incidence of further wheezing after RSV. Further
      studies on RSV should address these questions in more detail. RSV is an important
      pathogen ill young children in tropical and developing countries and a frequent
      cause of hospital admission. Prevention of RSV infection by vaccination would
      have a significant impact on the incidence of ALRI in children in developing
      countries.

PMID- 9623928
TI  - The effect of chemoprophylaxis on the timing of onset of falciparum malaria.
AB  - The association between chemoprophylaxis and delayed onset of falciparum malaria
      was investigated in a retrospective study of 477 nonimmune cases reported to the
      UK Malaria Reference Laboratory (MRL) who had used either mefloquine (n = 56),
      chloroquine-proguanil (n = 90) or no chemoprophylaxis (n = 331). For holiday and
      short-term travellers using mefloquine the time between arrival in the UK and
      diagnosis was found to be significantly longer than for chloroquine and proguanil
      (C-P) users or for those who had not used prophylaxis at all (P < 0.004). This
      delay was primarily due to a later onset of symptoms. C-P use was not associated
      with delay in onset of symptoms or diagnosis when compared to not using
      prophylaxis. Possible reasons for the findings are discussed. Mefloquine may
      continue to exert a partially suppressive effect on resistant strains of
      Plasmodium falciparum (Pf). That chloroquine with proguanil was not found to have
      such an effect may be due to poor compliance to proguanil or differences in the
      mode of action and range of parasite resistance to the two regimens. Differences
      in drug compliance may be one reason why only mefloquine users on holiday or
      short-term journeys experienced delays to onset of disease. Drug compliance
      amongst cases of breakthrough malaria on chemoprophylaxis may be lower than is
      generally recognized. It is important for clinicians and travellers to be aware
      that the onset of falciparum malaria may be delayed by mefloquine prophylaxis.

PMID- 9623929
TI  - Relative versus absolute risk of dying reduction after using insecticide-treated
      nets for malaria control in Africa.
AB  - Four recently completed large-scale randomized controlled trials have assessed
      the impact of insecticide-treated bednets and curtains on overall child mortality
      in Africa. These results have sparked numerous discussions among implementing
      agency representatives and researchers about the public health significance of
      the results. For the interpretation of impact, most of the arguments have been
      based on the observed decrease in protective efficacy (a relative measure of
      impact) with increasing malaria transmission (range: 14-29%, regression for
      trend: F = 245 on 1,2 DF, P < 0.003). However, an analysis of the absolute
      measure of impact (the risk difference) showed a different pattern. The impact
      ranges from 3.8 to 6.9 lives saved per 1000 children protected per year, without
      a significant trend (F = 2.8 on 1,2 DF, P = 0.2) and with equally high values in
      both low and high transmission sites. When assessing the public health importance
      of an intervention, both relative and absolute decrease in risk should be
      considered.

PMID- 9623930
TI  - Improved injection practices after the introduction of treatment and sterility
      guidelines in Tanzania.
AB  - OBJECTIVE: To evaluate the effect of introduction of treatment and sterilization
      guidelines on the number of avoidable injections and on the sterility of needles
      and syringes. METHODS: In 1991, 66 randomly selected health units in Mwanza
      Region, Tanzania, were visited and factors were determined that might contribute
      to HIV transmission by injections. In a workshop with all senior health workers
      from the region, findings were presented and treatment and sterilization
      guidelines developed. Thereafter, seminars were held at each health centre of the
      region. Four months after the intervention, data were collected at the same
      health facilities in order to assess changes in prescribing practices,
      sterilization procedures, and sterility of needles and syringes. RESULTS: The
      knowledge on indications for injections improved markedly for paramedical staff.
      The proportion of outpatients receiving an injection dropped from 23% to 10% and
      the proportion of patients receiving an avoidable injection dropped from 16% to
      6%. Procedures for sterilization, keeping sterilized equipment, and
      administration of injections improved. A smaller proportion of sterilized needles
      and syringes tended to be contaminated in dispensaries, but this reduction from
      44% to 22% was not significant. CONCLUSION: Considerable improvement in
      knowledge, prescription practices and sterility procedures was observed at
      dispensary level after carrying out a training programme.

PMID- 9623931
TI  - Low overall mortality of Turkish residents in Germany persists and extends into a
      second generation: merely a healthy migrant effect?
AB  - OBJECTIVE: To test the hypothesis that as a minority with lower socio-economic
      status, Turkish residents in Germany might experience a higher mortality than
      Germans. METHODS: All-cause mortality rates by age group and sex of Turkish and
      German adults for the time period 1980-94 were calculated from death registry
      data and mid-year population estimates. RESULTS: The age-adjusted mortality rate
      (per 100000) of Turkish males aged 25-65 years resident in Germany was 299 in
      1980 and 247 in 1990, consistently half that of German males. The mortality of
      Turkish females in Germany was 140 in 1990, half that of German females.
      Mortality of Turkish males/females in Ankara was 835 and 426 in 1990. CONCLUSION:
      In view of the socio-economic status of Turkish residents in Germany the large
      mortality difference compared to Germans is unexpected. It cannot be fully
      explained by a selection at the time of hiring (healthy migrant effect) because
      it lasts over decades and extends into the second generation. A healthy worker
      effect is unlikely because Turkish residents have a lower employment rate than
      Germans. There is little evidence for movement of gravely ill persons back to
      Turkey. An 'unhealthy re-migration effect' in which socially successful migrants
      with a lower mortality risk stay in the host country while less successful ones
      return home even before becoming manifestly ill would partly explain our
      findings.

PMID- 9623932
TI  - High prevalence of Plasmodium malariae and Plasmodium ovale in malaria patients
      along the Thai-Myanmar border, as revealed by acridine orange staining and PCR
      based diagnoses.
AB  - The prevalence of the four human malaria parasites was investigated among malaria
      patients at northern, central and southern towns in Thailand along the border
      with Myanmar between September 1995 and May 1996. Thin smears obtained from 548
      Thai and Burmese patients were reviewed by an acridine orange staining method,
      and many mixed infections with two to four species, including P. malariae and P.
      ovale, were detected. These diagnostic results were compared with those by two
      PCR-based diagnoses, microtitre plate hybridization (MPH) and a nested PCR
      method, both of which targets the same, species-specific regions in the 18S rRNA
      genes. In both PCR diagnoses, many P. malariae and P. ovale infections were also
      detected. Detection sensitivity of P. malariae infection was higher in nested PCR
      than MPH, and a total prevalence of P. malariae infection estimated by nested PCR
      reached 24.3% (133/548). In 16 of them, the size of PCR products amplified by the
      P. malariae-specific primer was about 20-bp shorter than the expected size of 115
      bp. Four of 16 possessed two different bands with normal and shorter sizes,
      suggesting that P. malariae isolates may be separated into two types, and that
      those with shorter products may be new variant form (s) with a nucleotide
      deletion in the target region. On the other hand, 21 P. ovale infections (3.8%)
      were detected by nested PCR, but four of them were MPH-negative because of the
      sequence variation at the probe region. These results indicated that the
      prevalence of P. malariae and P. ovale along the Thai-Myanmar border may be
      substantially higher than previously reported.

PMID- 9623933
TI  - IgG4 serology of loiasis in three villages in an endemic area of south-eastern
      Gabon.
AB  - Human filariasis due to Loa loa differs from other filariasis in that the
      majority of infected subjects are without circulating microfilariae (occult
      loiasis). In search for alternative diagnostic methods, which do not depend on
      circulating microfilariae or the (rather infrequent) eye-passage of adult worms,
      it was shown earlier that IgG4 antibodies directed against Loa loa adult worm
      antigen are apparently a good marker of occult loiasis and specific with regard
      to the sympatrically occurring Mansonella perstans. In this study we evaluated an
      IgG4 antibody-based ELISA using crude extract of Loa loa microfilariae (which is
      easier to obtain than adult worm) to estimate the prevalence of loiasis in 3
      villages in South-East Gabon. Of 222 examined individuals (80 children < 16
      years, 142 adults) 44 (20%) carried Loa loa microfilariae and 170 (77%) M.
      perstans. Using the mean OD-value + 1 standard deviation of 9 sera from patients
      solely infected with M. perstans (from the Gambia, where Loa loa is not endemic)
      as a cut-off, 35 of the 44 microfilaraemic Loa loa patients and 2 of the 9
      Gambian controls were positive. This shows that our method had a sensitivity of
      80% and a specificity of 78%. Among the remaining 178 subjects who had no
      microfilariae of Loa loa, as many as 97 (55%) had significant levels of specific
      IgG4 antibodies against Loa loa, suggesting that they carried occult loiasis. The
      mean IgG4 level in these putatively occult loiasis patients was slightly but
      significantly lower than in microfilaraemic subjects (P < 0.03). In conclusion,
      despite the limited sensitivity and specificity of our method, IgG4- ELISA at
      present is a very useful tool in estimating the real prevalence of loiasis in
      epidemiological surveys and at the individual level can confirm the diagnosis of
      L. loa amicrofilaraemic subjects with clinical signs suggesting loiasis.

PMID- 9623934
TI  - Human IgE responses to rSm22.6 are associated with infection intensity rather
      than age per se, in a recently established focus of Schistomiasis mansoni.
AB  - In studies of schistosomasis mansoni-endemic communities, individuals with IgE
      responses to a 22 kD adult worm antigen (rSm22.6) suffered lower intensities of
      reinfection after treatment. It is of interest to define the factors that lead to
      the production of rSm22.6-specific IgE because it is a marker for resistant
      individuals and it may be involved in the development of resistance to
      reinfection. In endemic populations rSm22.6-specific IgE increases linearly with
      age. However, it is not possible to distinguish between age per se and 'history
      of infection' in endemic populations because individuals are exposed to the
      parasite at an early age. We have, therefore, quantified pre- and post-treatment
      isotype responses to rSm22.6 in a comparatively 'epidemic' Senegalese community
      where the patients were infected at different ages and where pre-treatment
      intensity of infection can be taken as a reasonable measure of antigen exposure.
      Post-treatment isotype responses to rSm22.6 correlated positively with pre
      treatment intensities of infection but were not shown to be related to age. IgG1,
      IgG4 and IgE responses to rSm22.6 were significantly higher after treatment with
      the difference increasing with the pre-treatment level of infection. These
      results from a recently established focus of infection suggest that isotype
      responses to rSm22.6 are antigen-exposure dependent rather than dependent on age
      per se.

PMID- 9623935
TI  - Clinical findings in female genital schistosomiasis in Madagascar.
AB  - To assess the morbidity of S. haematobium infection in women of reproductive age
      (15-49 years) in the western part of Madagascar, the village of Betalatala with a
      prevalence of urinary schistosomiasis in women of 75.6% (95% confidence limit
      69.3 to 81.9%) was compared with a neighbouring village with similar socio
      economic characteristics and a prevalence of 5.0% (95% confidence limit 0 to
      11.75%). The women were questioned in Malagasy about obstetrical history and
      urogynecological symptoms. They were examined gynaecologically, parasitologically
      and by ultrasonography. Important STDs were excluded by appropriate diagnostics.
      In Betalatala significantly more women reported a history of spontaneous abortion
      (P < 0.01), complaints of irregular menstruation (P < 0.001), pelvic pain
      (<0.05), vaginal discharge (P < 0.0001), dysuria (P < 0.05) and haematuria (P <
      0.01) than in the control village. Biopsies were obtained from the cervix of 36
      women with macroscopical lesions, and in 12 cases S. haematobium eggs were found
      by histological sectioning (33.3%). In the control village no eggs were detected
      in the histological sections of biopsies taken from 14 women. (P < 0.05).
      Infections with Candida albicans, Trichomonas vaginalis, Gardnerella vaginalis
      and Treponema pallidum were found in similar frequencies in both villages. In
      9.8% of the women in Betalatala abnormalities of the upper reproductive tract
      were revealed by ultrasonography versus none in the women from the control
      village (P < 0.05). Echographic abnormalities of the urinary tract were present
      in 24% and 3% of the women in the study village and in the control village,
      respectively (P < 0.0001). These findings were accompanied by an elevated
      frequency of haematuria (55% versus 20%) and proteinuria (70.4% versus 25%) in
      the study population (P < 0.0001). Our study indicates that S. haematobium
      infection in women may not only cause symptoms in the urinary tract, but also
      frequently in the lower and upper reproductive tract.

PMID- 9623936
TI  - Attacking poverty and improving health: a report on the WHO/State of Maryland
      International Health Congress, Baltimore, September 1997.
AB  - An international meeting, 'Investment Strategies for Healthy Urban Communities',
      in Baltimore in September 1997 called on the the business community, city
      authorities and the health professions to reduce poverty and its adverse health
      consequences, especially in urban areas, in both the industrialized and
      developing world. In addition to issuing the Baltimore Charter on partnership for
      a healthy urban future, the meeting had two main outcomes: the innovative concept
      of Business for Health, championed by progressive business leaders from
      Australia, Europe and the United States, to promote business principles to reduce
      poverty, create enterprises and improve people's health, especially in developing
      countries; and the establishment by health professionals of an information
      network between cities and countries on poverty and ill-health. Two follow-up
      meetings in London in December 1997 resulted in an action plan to create networks
      of health professional groups and representatives of the business community.

PMID- 9623937
TI  - We have a cancer vaccine--why don't we use it?

PMID- 9623938
TI  - Novel, sensitive and low-cost diagnostic tests for 'river blindness'--detection
      of specific antigens in tears, urine and dermal fluid.
AB  - Sensitive, specific and low-cost diagnostic tests for onchocerciasis are
      indispensable for monitoring the efficacy of control programs, as well as for
      preventing blindness (when the tests are combined with efficacious chemotherapy.
      Three new tests to detect Onchocerca-specific antigens in tears, dermal fluid and
      urine employ antibodies to O. volvulus-specific recombinant proteins, Oncho-C27
      and OvD3B, encoded by genes within the immunodominant Onchocerca OV 33-3 gene
      family, and expressed in yeast and in E. coli, respectively. In these assays,
      Onchocerca-specific antigens in test samples are bound onto a solid surface and
      revealed using appropriate enzyme-labelled antibodies. Proteins in the samples
      are first transferred to Hybond-N + membrane disks or nitrocellulose paper using
      either a transblot or a dotblot machine, and then reacted with specific O.
      volvulus antibodies. Bound antibodies are revealed with species-specific
      peroxidase-labelled antibodies and peroxidase substrate. Positive tests give a
      brown colour. In one of the two assays developed to detect Onchocerca antigens in
      tears, the sensitivity was enhanced by first adsorbing the specific antibodies
      onto the membrane surface in order to immobilize and concentrate the Onchocerca
      specific antigen molecules on the membrane. The specificity of the recombinant
      proteins for Onchocerca volvulus had been verified by ELISA, classical Western
      blot and modified DSIA. The tests are a dipstick immunobinding assay for ocular
      microfilariae (DSIA), a transblot immunobinding assay for the detection of skin
      microfilariae (TADA) and a dot-blot immunobinding assay for detecting urinary
      microfilariae and their antigens (DIA). Their specificity and sensitivity were
      evaluated in the field on 110 subjects with proven ocular microfilariae, 130
      subjects with clinical and parasitological evidence of onchocerciasis, 25
      subjects infected with other helminths and 120 normal controls. The minimal
      detection limits of Oncho-C27 protein by DSIA, TADA and DIA were 500 ng/ml, 154
      ng/ml and 508 ng/ml, respectively By contrast, their sensitivities were: 100% for
      DSIA and 82.5% for TADA employed on samples of tears; 97% for TADA skin test and
      96% for DIA used on urine samples.

PMID- 9623939
TI  - Injury control in Africa: getting governments to do more.
AB  - Despite increasing recognition of injury as a major public health problem
      worldwide, it has received limited attention and resources. This lack of
      attention is most notable in low-income countries. As part of efforts to develop
      coordinated injury control activities in Africa, a round table session was held
      at the Third International Conference on Injury Prevention and Control in
      Melbourne, Australia. The aims of the forum were to provide injury control
      researchers from Africa the opportunity to come together and reflect on issues of
      injury control in Africa, to deliberate on strategies of getting African
      governments to show more interest in injury control, and to solicit more
      assistance from the international donor community Participants from Ghana, Kenya,
      South Africa and Zimbabwe presented the magnitude of the injury burden in their
      respective countries, reflected on current research efforts and highlighted the
      preventive efforts being undertaken. The forum made many recommendations
      including several regarding specific actions required of African governments,
      individual researchers and donor agencies.

PMID- 9623940
TI  - Effectiveness of chemoprophylaxis and other determinants of malaria in travellers
      to Kenya.
AB  - OBJECTIVE: To investigate the effectiveness of chemoprophylaxis and the
      determinants of malaria importation from Kenya. METHOD: In a population-based
      case-control study, 51 travellers from Bavaria diagnosed with falciparum malaria
      imported from Kenya (cases) and a sample of 383 healthy Bavarian travellers
      returning from Kenya (controls) were interviewed. Data were analysed by multiple
      logistic regression. RESULTS: Mefloquine (OR = 0.055; 95% CI 0.019-0.16) and
      chloroquine combined with proguanil (OR = 0.128; 95% CI 0.039-0.419) were highly
      protective against P. falciparum malaria, whereas other drugs were ineffective
      (OR = 1.225; 95% CI 0.536-2.803). Ineffective prophylaxis (10.4%) and non
      prophylaxis (11.2%) were the main reasons for malaria importation. Travelling
      alone or with friends, male sex, and travel duration over 4 weeks could be
      identified as additional risk factors. The main reason for inadequate
      chemoprophylaxis was inappropriate medical advice (87.5%). Prophylaxis refusal
      occurred frequently despite correct advice (58.1%). Diagnosis was often delayed
      unnecessarily (27.5%). CONCLUSION: Malaria importation from Kenya could be
      reduced substantially (34%) by eliminating inappropriate medical advice.

PMID- 9623941
TI  - Cryptic speciation in Triatoma sordida (Hemiptera:Reduviidae) from the Bolivian
      Chaco.
AB  - Eight natural Bolivian populations of two closely related species of Triatominae,
      Triatoma sordida and T. guasayana, were analysed by multilocus enzyme
      electrophoresis at 20 loci. Both species were readily separated and no natural
      hybrid was observed. Among the silvatic sample of T. sordida, strong departure
      from panmixia within and between loci was detected in two sites of the Chaco,
      suggesting two reproductively separate populations easily recognized at Idh2 and
      Mdh2 loci. Genetic distance between them was in agreement with the hypothesis of
      distinct species. However, the detection of 3% of putative hybrids suggested a
      recent evolutionary divergence.

PMID- 9623942
TI  - Tandemly repeated genomic sequence demonstrates inter- and intra-strain genetic
      variation in Schistosoma japonicum.
AB  - Genetic variability within and among four geographical strains of Schistosoma
      japonicum was examined using a novel repetitive element. The element, termed
      Sirh1.0, was isolated from genomic DNA of a Philippine strain of S. japonicum
      using a combination of restriction fragment PCR and band-stab PCR. Sjrh1.0 is a
      tandemly repeated element, the sequence of which appears to be species-specific,
      in that it hybridized to DNA from S. japonicum but not to DNA from S. mansoni.
      Its sequence does not match previously deposited sequences in GenBank. When
      employed as a probe in Southern hybridization analysis, radiolabelled Sjrh1.0
      revealed sex-specific and strain-specific differences in genomic DNA of
      individual worms. We also found individual genetic variation within geographical
      isolates of the Asian schistosome.

PMID- 9623943
TI  - In vitro sensitivity of Plasmodium falciparum to halofantrine compared with
      chloroquine, quinine and mefloquine in the region of Bobo-Dioulasso, Burkina Faso
      (West Africa).
AB  - The in vitro sensitivity of P. falciparum drug-resistant isolates was evaluated
      in the region of Bobo-Dioulasso during the 1995 and 1996 rainy seasons. Two
      routinely used antimalarials (chloroquine and quinine) and two new antimalarials
      (mefloquine and halofantrine) were assessed using 24-hour in vitro cultures with
      tritiated hypoxanthine and a parasite density > or = 4,000/microl of blood. The
      proportion of chloroquine-resistant isolates was 20% in 1995 and 19% in 1996,
      whilst in 1996, the proportion of isolates resistant to halofantrine was greater
      than in 1995 (9.6% versus 1%). No significant differences were seen in the mean
      IC50 values in relation to the susceptibility of chloroquine-resistant or
      chloroquine-sensitive isolates to mefloquine and halofantrine. In the case of
      quinine, the mean IC50 values were significantly higher in chloroquine-resistant
      isolates than in chloroquine-sensitive ones. A significant positive correlation
      was found between the following IC50 values: chloroquine versus quinine, quinine
      versus mefloquine and mefloquine versus halofantrine.

PMID- 9623944
TI  - Cytopathic effects of Blastocystis hominis on Chinese hamster ovary (CHO) and
      adeno carcinoma HT29 cell cultures.
AB  - Blastocystis hominis isolates from asymptomatic carriers and symptomatic patients
      were cultured in vitro, purified from the co-cultivated bacterial flora and
      tested for cytopathic effects on monolayers of Chinese Hamster Ovary (CHO) cells
      and Adeno Carcinoma HT29 cells. In the case of the CHO cells, living B. hominis
      cells and B. hominis cell lysates were able to cause significant cytopathic
      effects, which were dependent on the concentration of cells employed. Destruction
      of the cell monolayers was observed to the same extent with patient isolates
      derived from healthy or symptomatic B. hominis carriers. HT29 cells were less
      susceptible: B. hominis cells and cell lysates caused only minor effects which
      were not statistically significant. Culture filtrates of B. hominis exhibited
      cytopathic potential on CHO and HT29 cells; however, the control which consisted
      of filtrates from Robinson's cultures in which B. hominis failed to grow showed
      similar effects, too. Therefore the culture supernatants could not be proven to
      produce a specific cytopathic effect on CHO and HT29 cells.

PMID- 9623945
TI  - Causes of locomotor disability and need for orthopaedic devices in a heavily
      mined Taliban-controlled province of Afghanistan: issues and challenges for
      public health managers.
AB  - We conducted a locomotor disability survey on a heavily mined Taliban-controlled
      province of Afghanistan to document the problem of locomotor disability and to
      assess the need for orthopaedic rehabilitation devices in a study population of
      12065. Global prevalence of locomotor disability was 23/1000 (95% CI: 20-26).
      )War-related injuries were the leading cause of disability, affecting almost
      exclusively adult males. Leading causes of disability among women and children
      were medical and poliomyelitis. Devices most needed were lower limb ortheses (8.2
      devices/1000 people; 95% CI: 5.9-10.4) and orthopaedic shoes (6.0/1000; 95%
      CI:4.1-8.0). The need for lower limb prostheses was less frequent (2.0/1000; 95%
      CI: 1.1-2.8). Most lower limb amputees (mainly victims of landmine injuries) were
      fitted with an artificial leg, while rehabilitation needs for other types of
      disability remained largely unmet. We estimated that it would take at least 3
      years to provide enough orthopaedic shoes and 10 years for ortheses, whereas the
      need for lower limb prostheses could be met in less than 4 months. None of the 27
      women with lower limb disability were equipped with an orthopaedic device,
      although this was the case for 31 of 89 men (35%). The problem of landmines
      should not divert attention from other causes of disability such as poliomyelitis
      or from other rehabilitation requirements. Immunization programmes and
      restoration of the public health infrastructure should be given high priority;
      rehabilitation services are largely insufficient and should be developed. Extreme
      gender difference in needs coverage is a matter of concern. Researching
      culturally sensitive strategies to tackle this problem should be a priority for
      donors and implementing agencies.

PMID- 9623946
TI  - Chemotherapy for onchocerciasis: results of in vitro experiments with promising
      new compounds.
AB  - An improved short-term in vitro culture system was used for the routine screening
      of hundreds of promising new compounds with the target organism, the filarial
      nematode Onchocerca volvulus. The most active leads were identified among the
      pyrimidinylguanidines, amidine derivatives, the imidazolinylhydrazones,
      thiosemicarbazone derivatives and thiadiazole derivatives. Single compounds of
      these leads demonstrated strong macrofilaricidal efficacy in minimum effective
      dose trials down to 0.1 microM and in experiments evaluating the minimum time of
      exposure after less than 6 h exposure. In the group of the pyrimidinylguanidines
      we found a significant correlation of structure and activity: change of a single
      side-group in the molecules had dramatic influence on compound activity. Most of
      the new compounds that were active on the macrofilariae did not show significant
      activity on microfilariae (mf) in in vitro trials. Only one compound with
      significant activity against female O. volvulus worms killed mf at very low
      concentrations. Some of the promising leads will be processed in further trials
      on a preclinical level with predictive cattle models.

PMID- 9623947
TI  - Susceptibility of severe combined immuno-deficient (SCID) mice to Trypanosoma
      brucei gambiense and T. b. rhodesiense.
AB  - Susceptibility of severe combined immunodeficient (SCID) mice to 7 isolates of
      Trypanosoma brucei gambiense and 2 isolates of T. b. rhodesiense was examined in
      terms of their infectivity, course of parasitaemia, packed cell volume (PCV) and
      survival period in comparison with that of normal immunocompetent (BALB/c) mice.
      All isolates of T. b. gambiense and T. b. rhodesiense caused high (> 1 x 10(8)
      parasites/ml) parasitaemia in the SCID mice, the survival periods ranged from 5
      to 47 days. On the other hand, 5 of 7 isolates of T. b. gambiense developed
      chronic infection in the BALB/c mice with sporadic but persistent parasitaemia
      with less than 5 x 10(6) parasites/ml. All the mice tested in this group survived
      more than 60 days after infection. In contrast, the 2 remaining isolates of T. b.
      gambiense and both isolates of T. b. rhodesiense showed high virulence in the
      BALB/c mice and killed all of them within 30 days after infection. The results
      demonstrate that the SCID mice, in which functional B- and T-cell-mediated
      immunities are congenitally lacking, are highly susceptible for 'low-virulence'
      T. b. gambiense. This makes SCID mice useful tools for the isolation of parasites
      from T. b. gambiense sleeping sickness patients and the propagation of large
      amounts of such parasites.

PMID- 9623948
TI  - Patterns of treatment for malaria in Tayabas, The Philippines: implications for
      control.
AB  - This paper describes local understandings of illness and documents treatment
      seeking behaviour in Tayabas, Quezon, The Philippines. Data were collected using
      focus group discussions and narrative interviews with adults and with mothers of
      children, who had had confirmed malaria during a two-month surveillance period.
      Signs and symptoms of malaria are important in directing individual diagnosis,
      treatment-seeking and therapy. Household therapy with antimalarials, and more
      commonly antipyretics and herbs, as used before seeking care from either the
      formal or informal sector. Care outside the home was sought where symptoms
      continued and/or worsened, with an average period of time from onset of symptoms
      to presentation to a clinic of six days. Accessibility to clinics is not a
      problem in the study area and hence the primary reason for delay was propensity
      to self-treat first and to discontinue medication when feeling better. These
      factors affect the control of malaria and the potential to reduce transmission.
      Better advice to the community regarding the importance of diagnosis and
      compliance with antimalarial therapy is indicated.

PMID- 9623949
TI  - Molecular medicine growing pains.

PMID- 9623950
TI  - A role for IL-15 in rheumatoid arthritis?

PMID- 9623951
TI  - Human cloning: safety is the issue.

PMID- 9623952
TI  - Cross-species infection: no news is good news?

PMID- 9623953
TI  - External stenting & atherosclerosis.

PMID- 9623954
TI  - Hypocretins or hyporexins?

PMID- 9623955
TI  - Tamoxifen, raloxifene findings unlikely to encourage genetic screening for breast
      cancer.

PMID- 9623956
TI  - Science versus politics...in US needle exchange program.

PMID- 9623957
TI  - Science versus politics...in HIV vaccine development.

PMID- 9623958
TI  - Bill paves the way for more birth defects research.

PMID- 9623959
TI  - McVie calls for reduction in cancer charity numbers.

PMID- 9623960
TI  - Australian laws frustrate bioprospectors.

PMID- 9623961
TI  - UK leads on science and technology bioethics.

PMID- 9623962
TI  - The science of art and vice versa.

PMID- 9623963
TI  - Will new guidelines protect or expose the Indian gene pool?

PMID- 9623964
TI  - The next frontier of molecular medicine: delivery of therapeutics.

PMID- 9623965
TI  - Nicotine addiction and the lure of reward.

PMID- 9623966
TI  - Playing with dopamine release.

PMID- 9623967
TI  - Calcineurin--the missing link in cardiac hypertrophy.

PMID- 9623968
TI  - The CFTR advantage--capitalizing on a quirk of fate.

PMID- 9623969
TI  - To treat or not to treat?

PMID- 9623970
TI  - Exposing gliadin as a tasty food for lymphocytes.

PMID- 9623971
TI  - Idiotype vaccines: forgotten but not gone.

PMID- 9623972
TI  - Neuronal grafts for Huntington's disease.

PMID- 9623973
TI  - The how and Y of eating.

PMID- 9623975
TI  - Predicting and preventing the emergence of antiviral drug resistance in HSV-2.
AB  - Genital herpes, caused by herpes simplex virus, is the most prevalent sexually
      transmitted disease worldwide. In many developing countries genital herpes is
      untreated, and in the United States only 10% of cases are treated. We present a
      mathematical model that we use as a health policy tool to predict the levels of
      antiviral drug resistance that would emerge, if treatment rates were increased,
      and to identify the key factors in determining the emergence of drug resistance.
      We use our results to suggest control measures for herpes epidemics that would
      prevent the emergence of substantial levels of antiviral drug resistance.

PMID- 9623976
TI  - A role for carbohydrates in immune evasion in AIDS.
AB  - Rhesus monkeys were infected with mutant forms of simian immunodeficiency virus
      lacking dual combinations of the 4th, 5th and 6th sites for N-linked
      glycosylation in the external envelope glycoprotein of the virus. When compared
      with sera from monkeys infected with the parental virus, sera from monkeys
      infected with the mutant viruses exhibited markedly increased antibody binding to
      specific peptides from this region and markedly increased neutralizing activity.
      These results demonstrate a role for N-linked glycosylation in limiting the
      neutralizing antibody response to SIV and in shielding the virus from immune
      recognition.

PMID- 9623977
TI  - Overexpression of E2F-1 in glioma triggers apoptosis and suppresses tumor growth
      in vitro and in vivo.
AB  - The transfer of apoptosis genes to tumors is one of the most promising strategies
      for cancer gene therapy. We have shown that massive apoptosis occurs when wild
      type p53 expression is induced in glioma cells carrying a p53 gene mutation.
      However, adenovirus-mediated p53 gene transfer is ineffective in causing
      apoptosis in glioma cells that retain a wild-type p53 genotype. We evaluated the
      effect of E2F-1 overexpression on the growth of gliomas in vitro and in vivo. In
      the in vitro study, the adenovirus-mediated transfer of exogenous E2F-1 protein
      precipitated generalized apoptosis in gliomas. The treatment with Ad5CMV-E2F-1 of
      nude mice carrying subcutaneous gliomas arrested tumor growth. Our results
      indicate that E2F-1 has anti-glioma activity in vitro and in vivo.

PMID- 9623978
TI  - Physiological degradation converts the soluble syndecan-1 ectodomain from an
      inhibitor to a potent activator of FGF-2.
AB  - The activity of fibroblast growth factor 2 (FGF-2) is stringently controlled.
      Inactive in undisturbed tissues, it is activated during injury and is critical
      for tissue repair. We find that this control can be imposed by the soluble
      syndecan-1 ectodomain, a heparan sulfate proteoglycan shed from cell surfaces
      into wound fluids. The ectodomain potently inhibits heparin-mediated FGF-2
      mitogenicity because of the poorly sulfated domains in its heparin sulfate
      chains. Degradation of these regions by platelet heparanase produces heparin-like
      heparin sulfate fragments that markedly activate FGF-2 mitogenicity and are found
      in wound fluids. These results establish a novel physiological control for FGF-2
      and suggest new ways to modulate FGF activity.

PMID- 9623980
TI  - Neonatal mouse immunity against group B streptococcal infection by maternal
      vaccination with recombinant anti-idiotypes.
AB  - We investigated whether immunization with recombinant anti-idiotypic antibody
      fragments mimicking the conformation of the capsular antigen can protect against
      infection by group B streptococcus, an important neonatal pathogen. Single-chain
      fragment-variable anti-idiotypes competed with the type III carbohydrate for
      binding to type-specific antibodies and elicited, in mice, the production of
      protective immunoglobulins reacting against the type III polysaccharide.
      Moreover, maternal immunization with soluble or phage-displayed fragments
      protected neonatal mice against streptococcal infection. These data indicate that
      recombinant anti-idiotypic antibodies may be useful in developing protein images
      of relevant carbohydrate epitopes and, ultimately, in preventing infections by
      encapsulated bacteria.

PMID- 9623979
TI  - Redox gene therapy for ischemia/reperfusion injury of the liver reduces AP1 and
      NF-kappaB activation.
AB  - Liver transplantation is the only therapeutic strategy for many inherited and
      acquired diseases. The formation of reactive oxygen species following
      ischemia/reperfusion is a cause of hepatocellular injury during transplantation.
      This report describes the therapeutic application of mitochondrial superoxide
      dismutase gene transfer to the liver for acute ischemia/reperfusion injury.
      Recombinant adenoviral expression of mitochondrial superoxide dismutase in mouse
      liver prior to lobar ischemia/reperfusion significantly reduced acute liver
      damage and associated redox activation of both NF-kappaB and AP1. These immediate
      early transcription factors represent common pathways by which cells respond to
      environmental stress. This work provides the foundation for redox-mediated gene
      therapies directed at ameliorating ischemia/reperfusion injury and associated
      acute rejection in orthotopic liver transplantation.

PMID- 9623981
TI  - Idiotypic immunization induces immunity to mutated p53 and tumor rejection.
AB  - The p53 molecule might serve as a common tumor-associated antigen, as the tumor
      suppressor gene p53 is mutated and the p53 protein is often over-expressed in
      tumor cells. We report that effective immunity to p53 can be induced through an
      idiotypic network by immunization of mice with a monoclonal antibody (PAb-240)
      specific for mutated p53, or with a peptide derived from the complementarity
      determining region (CDR) 3 of the variable domain of the light chain (VL) of this
      antibody. The immunized mice produced IgG antibodies to p53 and mounted a
      cytotoxic reaction to a tumor line bearing mutated p53. The idiotypically
      immunized mice were resistant to challenge with the tumor cells. Thus antibodies
      to p53 might serve as immunogens for activating resistance to some tumors. At the
      basic level, these findings indicate that a network of p53 immunity may be
      organized naturally within the immune system.

PMID- 9623982
TI  - Tissue transglutaminase selectively modifies gliadin peptides that are recognized
      by gut-derived T cells in celiac disease.
AB  - The action of tissue Transglutaminase (TGase) on specific protein-bound glutamine
      residues plays a critical role in numerous biological processes. Here we provide
      evidence for a new role of this enzyme in the common, HLA-DQ2 (and DQ8)
      associated enteropathy, celiac disease (CD). The intestinal inflammation in CD is
      precipitated by exposure to wheat gliadin in the diet and is associated with
      increased mucosal activity of TGase. This enzyme has also been identified as the
      main target for CD-associated anti-endomysium autoantibodies, and is known to
      accept gliadin as one of its few substrates. We have examined the possibility
      that TGase could be involved in modulating the reactivity of gliadin specific T
      cells. This could establish a link between previous reports of the role of TGase
      in CD and the prevailing view of CD as a T-cell mediated disorder. We found a
      specific effect of TGase on T-cell recognition of gliadin. This effect was
      limited to gliadin-specific T cells isolated from intestinal CD lesions. We
      demonstrate that TGase mediates its effect through an ordered and specific
      deamidation of gliadins. This deamidation creates an epitope that binds
      efficiently to DQ2 and is recognized by gut-derived T cells. Generation of
      epitopes by enzymatic modification is a new mechanism that may be relevant for
      breaking of tolerance and initiation of autoimmune disease.

PMID- 9623983
TI  - Role of the Y5 neuropeptide Y receptor in feeding and obesity.
AB  - Neuropeptide Y (NPY), a 36-amino-acid neuromodulator abundantly expressed in the
      brain, has been implicated in the regulation of food intake and body weight.
      Pharmacological data suggest that NPY's stimulatory effect on appetite is
      transduced by the G-protein-coupled NPY Y5 receptor (Y5R). We have inactivated
      the Y5R gene in mice and report that younger Y5R-null mice feed and grow
      normally; however, they develop mild late-onset obesity characterized by
      increased body weight, food intake and adiposity. Fasting-induced refeeding is
      unchanged in younger Y5R-null mice and they exhibit normal sensitivity to leptin.
      Their response to intracerebroventricular (i.c.v.) administration of NPY and
      related peptides is either reduced or absent. NPY deficiency attenuates the
      obesity syndrome of mice deficient for leptin (ob/ob), but these effects are not
      mediated by NPY signaling through the Y5R because Y5R-null ob/ob mice are equally
      obese. These results demonstrate that the Y5R contributes to feeding induced by
      centrally administered NPY and its analogs, but is not a critical physiological
      feeding receptor in mice.

PMID- 9623984
TI  - Cardiovascular response, feeding behavior and locomotor activity in mice lacking
      the NPY Y1 receptor.
AB  - Neuropeptide Y (NPY) is a 36-amino-acid neurotransmitter which is widely
      distributed throughout the central and peripheral nervous system. NPY involvement
      has been suggested in various physiological responses including cardiovascular
      homeostasis and the hypothalamic control of food intake. At least six subtypes of
      NPY receptors have been described. Because of the lack of selective antagonists,
      the specific role of each receptor subtype has been difficult to establish. Here
      we describe mice deficient for the expression of the Y1 receptor subtype.
      Homozygous mutant mice demonstrate a complete absence of blood pressure response
      to NPY, whereas they retain normal response to other vasoconstrictors. Daily food
      intake, as well as NPY-stimulated feeding, are only slightly diminished, whereas
      fast-induced refeeding is markedly reduced. Adult mice lacking the NPY Y1
      receptor are characterized by increased body fat with no change in protein
      content. The higher energetic efficiency of mutant mice might result, in part,
      from the lower metabolic rate measured during the active period, associated with
      reduced locomotor activity. These results demonstrate the importance of NPY Y1
      receptors in NPY-mediated cardiovascular response and in the regulation of body
      weight through central control of energy expenditure. In addition, these data are
      also indicative of a role for the Y1 receptor in the control of food intake.

PMID- 9623985
TI  - Functional integration of striatal allografts in a primate model of Huntington's
      disease.
AB  - Huntington's disease is an autosomal dominant, inherited disorder that results in
      progressive degeneration of the basal ganglia (especially the neostriatal caudate
      nucleus and putamen) and other forebrain structures and is associated with a
      clinical profile of movement, cognitive and psychiatric impairments for which
      there is at present no effective therapy. Neuropathological, neurochemical and
      behavioral features of the disease can all be reproduced in experimental animals
      by local injection of excitotoxic or metabolic toxins into the neostriatum. All
      these features of the disease can be alleviated, at least in rats, by
      transplantation of embryonic striatal tissue into the degenerated striatum, which
      was the basis for commencing the first clinical trials of striatal
      transplantation in Huntington's patients. However, although rat striatal
      xenografts may temporarily reduce apomorphine-induced dyskinesias in monkeys,
      there has been no demonstration that allograft techniques that work well in rats
      translate effectively to the much larger differentiated striatum of primates.
      Here we demonstrate good survival, differentiation and integration of striatal
      allografts in the primate neostriatum, and recovery in a test of skilled motor
      performance. Long-term graft survival in primates indicates probable success for
      clinical transplants in Huntington's disease; in addition, our data suggest that
      graft placement has a direct influence on the pattern and extent of functional
      recovery.

PMID- 9623986
TI  - A detergent-insoluble membrane compartment contains A beta in vivo.
AB  - Ordered assembly of the amyloid-beta protein (A beta) into amyloid fibrils is a
      critical step in Alzheimer's disease (AD). To release the amyloidogenic peptide A
      beta from the Alzheimer amyloid precursor protein (APP), two secretases act
      sequentially: first, beta-secretase cleaves close to the membrane within the
      ectodomain and then gamma-secretase cuts within the transmembrane domain. The
      sites of gamma-secretase cleavage are after residues 40 or 42 of A beta. Except
      in those rare cases of AD caused by a mutation, levels of secreted A beta are not
      elevated; thus, the secretory pathway may be unaffected, and factors other than
      the extracellular concentration of A beta may contribute to the aggregation
      properties of the peptide. A beta is also present in intracellular compartments.
      The two gamma-secretase cleavage products, A beta42 and A beta40, were found in
      different compartments: A beta42 in the endoplasmic reticulum (ER)/intermediate
      compartment, and A beta40 in the trans-Golgi network (TGN). The cellular
      compartments that harbor A beta are target sites for therapeutic intervention.
      Here we report that in the brain, the principal compartment in which A beta
      resides is a detergent-insoluble glycolipid-enriched membrane domain (DIG). Also
      present in the DIG fractions are the endoproteolytic fragments of presenilin-1
      (PS1) and APP. The presence of these proteins, which all contribute to the
      generation of A beta, indicates that the DIG fraction is probably where the
      intramembranous cleavage of APP occurs.

PMID- 9623987
TI  - Gene therapy for therapeutic myocardial angiogenesis: a promising synthesis of
      two emerging technologies.

PMID- 9623988
TI  - 'Rough draft' of human genome wins researchers' backing.

PMID- 9623989
TI  - Authors slow to retract 'fraudulent' papers.

PMID- 9623990
TI  - Storm in Japan over sale of zoo monkeys for research.

PMID- 9623991
TI  - Lawsuit demands labels for modified foods.

PMID- 9623993
TI  - It's a small world.

PMID- 9623992
TI  - Swiss transgenic vote hangs in balance.

PMID- 9623994
TI  - Immunology. Licence to kill.

PMID- 9623995
TI  - A new image for fear and emotion.

PMID- 9623996
TI  - Vesalius's veracity.

PMID- 9623997
TI  - Vision and attention: the role of training.

PMID- 9623998
TI  - Collective dynamics of 'small-world' networks.
AB  - Networks of coupled dynamical systems have been used to model biological
      oscillators, Josephson junction arrays, excitable media, neural networks, spatial
      games, genetic control networks and many other self-organizing systems.
      Ordinarily, the connection topology is assumed to be either completely regular or
      completely random. But many biological, technological and social networks lie
      somewhere between these two extremes. Here we explore simple models of networks
      that can be tuned through this middle ground: regular networks 'rewired' to
      introduce increasing amounts of disorder. We find that these systems can be
      highly clustered, like regular lattices, yet have small characteristic path
      lengths, like random graphs. We call them 'small-world' networks, by analogy with
      the small-world phenomenon (popularly known as six degrees of separation. The
      neural network of the worm Caenorhabditis elegans, the power grid of the western
      United States, and the collaboration graph of film actors are shown to be small
      world networks. Models of dynamical systems with small-world coupling display
      enhanced signal-propagation speed, computational power, and synchronizability. In
      particular, infectious diseases spread more easily in small-world networks than
      in regular lattices.

PMID- 9623999
TI  - A one-million-year-old Homo cranium from the Danakil (Afar) Depression of
      Eritrea.
AB  - One of the most contentious topics in the study of human evolution is that of the
      time, place and mode of origin of Homo sapiens. The discovery in the Northern
      Danakil (Afar) Depression, Eritrea, of a well-preserved Homo cranium with a
      mixture of characters typical of H. erectus and H. sapiens contributes
      significantly to this debate. The cranium was found in a succession of fluvio
      deltaic and lacustrine deposits and is associated with a rich mammalian fauna of
      early to early-middle Pleistocene age. A magnetostratigraphic survey indicates
      two reversed and two normal magnetozones. The layer in which the cranium was
      found is near the top of the lower normal magnetozone, which is identified as the
      Jaramillo subchron. Consequently, the human remains can be dated at approximately
      1 million years before present.

PMID- 9624000
TI  - Physiology and molecular phylogeny of coexisting Prochlorococcus ecotypes.
AB  - The cyanobacterium Prochlorococcus is the dominant oxygenic phototroph in the
      tropical and subtropical regions of the world's oceans. It can grow at a range of
      depths over which light intensities can vary by up to 4 orders of magnitude. This
      broad depth distribution has been hypothesized to stem from the coexistence of
      genetically different populations adapted for growth at high- and low-light
      intensities. Here we report direct evidence supporting this hypothesis, which has
      been generated by isolating and analysing distinct co-occurring populations of
      Prochlorococcus at two locations in the North Atlantic. Co-isolates from the same
      water sample have very different light-dependent physiologies, one growing
      maximally at light intensities at which the other is completely photoinhibited.
      Despite this ecotypic differentiation, the co-isolates have 97% similarity in
      their 16S ribosomal RNA sequences, demonstrating that molecular microdiversity,
      commonly observed in microbial systems, can be due to the coexistence of closely
      related, physiologically distinct populations. The coexistence and distribution
      of multiple ecotypes permits the survival of the population as a whole over a
      broader range of environmental conditions than would be possible for a
      homogeneous population.

PMID- 9624001
TI  - Conscious and unconscious emotional learning in the human amygdala.
AB  - If subjects are shown an angry face as a target visual stimulus for less than
      forty milliseconds and are then immediately shown an expressionless mask, these
      subjects report seeing the mask but not the target. However, an aversively
      conditioned masked target can elicit an emotional response from subjects without
      being consciously perceived. Here we study the mechanism of this unconsciously
      mediated emotional learning. We measured neural activity in volunteer subjects
      who were presented with two angry faces, one of which, through previous classical
      conditioning, was associated with a burst of white noise. In half of the trials,
      the subjects' awareness of the angry faces was prevented by backward masking with
      a neutral face. A significant neural response was elicited in the right, but not
      left, amygdala to masked presentations of the conditioned angry face. Unmasked
      presentations of the same face produced enhanced neural activity in the left, but
      not right, amygdala. Our results indicate that, first, the human amygdala can
      discriminate between stimuli solely on the basis of their acquired behavioural
      significance, and second, this response is lateralized according to the subjects'
      level of awareness of the stimuli.

PMID- 9624002
TI  - The human amygdala in social judgment.
AB  - Studies in animals have implicated the amygdala in emotional and social
      behaviours, especially those related to fear and aggression. Although lesion and
      functional imaging studies in humans have demonstrated the amygdala's
      participation in recognizing emotional facial expressions, its role in human
      social behaviour has remained unclear. We report here our investigation into the
      hypothesis that the human amygdala is required for accurate social judgments of
      other individuals on the basis of their facial appearance. We asked three
      subjects with complete bilateral amygdala damage to judge faces of unfamiliar
      people with respect to two attributes important in real-life social encounters:
      approachability and trustworthiness. All three subjects judged unfamiliar
      individuals to be more approachable and more trustworthy than did control
      subjects. The impairment was most striking for faces to which normal subjects
      assign the most negative ratings: unapproachable and untrustworthy looking
      individuals. Additional investigations revealed that the impairment does not
      extend to judging verbal descriptions of people. The amygdala appears to be an
      important component of the neural systems that help retrieve socially relevant
      knowledge on the basis of facial appearance.

PMID- 9624003
TI  - A conditioned dendritic cell can be a temporal bridge between a CD4+ T-helper and
      a T-killer cell.
AB  - To generate an immune response, antigen-specific T-helper and T-killer cells must
      find each other and, because they cannot detect each other's presence, they are
      brought together by an antigen-loaded dendritic cell that displays antigens to
      both. This three-cell interaction, however, seems nearly impossible because all
      three cell types are rare and migratory. Here we provide a potential solution to
      this conundrum. We found that the three cells need not meet simultaneously but
      that the helper cell can first engage and 'condition' the dendritic cell, which
      then becomes empowered to stimulate a killer cell. The first step (help) can be
      bypassed by modulation of the surface molecule CD40, or by viral infection of
      dendritic cells. These results may explain the long-standing paradoxical
      observation that responses to some viruses are helper-independent, and they evoke
      the possibility that dendritic cells may take on different functions in response
      to different conditioning signals.

PMID- 9624004
TI  - Help for cytotoxic-T-cell responses is mediated by CD40 signalling.
AB  - Cytotoxic T lymphocytes (CTLs) which carry the CD8 antigen recognize antigens
      that are presented on target cells by the class I major histocompatibility
      complex. CTLs are responsible for the killing of antigen-bearing target cells,
      such as virus-infected cells. Although CTL effectors can act alone when killing
      target cells, their differentiation from naive CD8-positive T cells is often
      dependent on 'help' from CD4-positive helper T (TH) cells. Furthermore, for
      effective CTL priming, this help must be provided in a cognate manner, such that
      both the TH cell and the CTL recognize antigen on the same antigen-presenting
      cell. One explanation for this requirement is that TH cells are needed to convert
      the antigen-presenting cell into a cell that is fully competent to prime CTL.
      Here we show that signalling through CD40 on the antigen-presenting cells can
      replace the requirement for TH cells, indicating that T-cell 'help', at least for
      generation of CTLs by cross-priming, is mediated by signalling through CD40 on
      the antigen-presenting cell.

PMID- 9624005
TI  - T-cell help for cytotoxic T lymphocytes is mediated by CD40-CD40L interactions.
AB  - Although in vivo priming of CD8+ cytotoxic T lymphocytes (CTLs) generally
      requires the participation of CD4+ T-helper lymphocytes, the nature of the 'help'
      provided to CTLs is unknown. One widely held view is that help for CTLs is
      mediated by cytokines produced by T-helper cells activated in proximity to the
      CTL precursor at the surface of an antigen-presenting cell (APC). An alternative
      theory is that, rather than being directly supplied to the CTL by the helper
      cell, help is delivered through activation of the APC, which can then prime the
      CTL directly. CD40 and its ligand, CD40L, may activate the APC to allow CTL
      priming. CD40L is expressed on the surface of activated CD4+ T-helper cells and
      is involved in their activation and in the development of their effector
      functions. Ligation of CD40 on the surface of APCs such as dendritic cells,
      macrophages and B cells greatly increases their antigen-presentation and co
      stimulatory capacity. Here we report that signalling through CD40 can replace
      CD4+ T-helper cells in priming of helper-dependent CD8+ CTL responses. Blockade
      of CD40L inhibits CTL priming; this inhibition is overcome by signalling through
      CD40. CD40-CD40L interactions are therefore vital in the delivery of T-cell help
      for CTL priming.

PMID- 9624006
TI  - Role of Mxi1 in ageing organ systems and the regulation of normal and neoplastic
      growth.
AB  - Mxi1 belongs to the Mad (Mxi1) family of proteins, which function as potent
      antagonists of Myc oncoproteins. This antagonism relates partly to their ability
      to compete with Myc for the protein Max and for consensus DNA binding sites and
      to recruit transcriptional co-repressors. Mad(Mxi1) proteins have been suggested
      to be essential in cellular growth control and/or in the induction and
      maintenance of the differentiated state. Consistent with these roles, mxi1 may be
      the tumour-suppressor gene that resides at region 24-26 of the long arm of
      chromosome 10. This region is a cancer hotspot, and mutations here may be
      involved in several cancers, including prostate adenocarcinoma. Here we show that
      mice lacking Mxi1 exhibit progressive, multisystem abnormalities. These mice also
      show increased susceptibility to tumorigenesis either following carcinogen
      treatment or when also deficient in Ink4a. This cancer-prone phenotype may
      correlate with the enhanced ability of several mxi1-deficient cell types,
      including prostatic epithelium, to proliferate. Our results show that Mxi1 is
      involved in the homeostasis of differentiated organ systems, acts as a tumour
      suppressor in vivo, and engages the Myc network in a functionally relevant
      manner.

PMID- 9624008
TI  - A piece of my mind. God save the child.

PMID- 9624007
TI  - A cytokinesis checkpoint requiring the yeast homologue of an APC-binding protein.
AB  - Checkpoint controls ensure that events of the cell-division cycle are completed
      with fidelity and in the correct order. In budding yeast with a mutation in the
      motor protein dynein, the mitotic spindle is often misaligned and therefore slow
      to enter the neck between mother cell and budding daughter cell. When this
      occurs, cytokinesis (division of the cytoplasm into two) is delayed until the
      spindle is properly positioned. Here we describe mutations that abolish this
      delay, indicating the existence of a new checkpoint mechanism. One mutation lies
      in the gene encoding the yeast homologue of EB1, a human protein that binds the
      adenomatous polyposis coli (APC) protein, a tumour suppressor. EB1 is located on
      microtubules of the mitotic spindle and is important in spindle assembly. EB1 may
      therefore, by associating with microtubules, contribute to the sensor mechanism
      that activates the checkpoint. Another mutation affects Stt4, a
      phosphatidylinositol-4-OH kinase. Cold temperature is an environmental stimulus
      that causes misalignment of the mitotic spindle in yeast and appears to activate
      this checkpoint mechanism.

PMID- 9624010
TI  - Experts air new findings on lung diseases.

PMID- 9624009
TI  - Nature's agents help heal humans--some now take steps to reciprocate.

PMID- 9624011
TI  - From the Food and Drug Administration.

PMID- 9624012
TI  - From the Centers for Disease Control and Prevention. Measles--United States,
      1997.

PMID- 9624013
TI  - From the Centers for Disease Control and Prevention. Diagnosis and reporting of
      HIV and AIDS in states with integrated HIV and AIDS surveillance--United States,
      January 1994-June 1997.

PMID- 9624014
TI  - Memory loss--when is it Alzheimer disease?

PMID- 9624015
TI  - Rolling down the runway: the challenges ahead for quality report cards.
AB  - Today, steadily increasing numbers of hospitals and health plans are publicly
      releasing performance reports on the quality of care to permit comparisons across
      different providers. Our experience in recent years has provided important new
      evidence of what public quality reporting can accomplish and the difficulties it
      faces. Several years ago, the most important impediments to quality reporting may
      have been the availability of acceptable quality indicators and the feasibility
      of voluntary, standardized data collection by health plans. We have made strides
      in these areas. The Health Employer Data and Information Set (HEDIS) has
      expanded, and there have been new innovations in collecting data on quality from
      both patients and physicians. Hundreds of health plans have begun to report
      standardized quality data on a routine basis either voluntarily or in response to
      requirements from the Health Care Financing Administration, state Medicaid
      agencies, or private payers. Now, the more formidable barriers to the use of
      quality report cards may relate to the ways we report the data and use it. We
      need to find acceptable middle ground for those who believe information on
      individual physicians is critical and those who believe it is harmful. We need to
      reap the advantages in different modalities of data collection and different
      tools for quality management. Most of all, we need to find better ways to use
      quality reporting to empower purchasers and consumers and improve quality of
      care.

PMID- 9624016
TI  - Drug samples: benefit or bait?

PMID- 9624017
TI  - Role of apoptosis in health and disease.

PMID- 9624018
TI  - Role of apoptosis in health and disease.

PMID- 9624019
TI  - Universal health insurance.

PMID- 9624020
TI  - Zyban: two products, two uses--too confusing?

PMID- 9624021
TI  - Macular edema associated with nicotinic acid (niacin)

PMID- 9624022
TI  - Socioeconomic factors, health behaviors, and mortality: results from a nationally
      representative prospective study of US adults.
AB  - CONTEXT: A prominent hypothesis regarding social inequalities in mortality is
      that the elevated risk among the socioeconomically disadvantaged is largely due
      to the higher prevalence of health risk behaviors among those with lower levels
      of education and income. OBJECTIVE: To investigate the degree to which 4
      behavioral risk factors (cigarette smoking, alcohol drinking, sedentary
      lifestyle, and relative body weight) explain the observed association between
      socioeconomic characteristics and all-cause mortality. DESIGN: Longitudinal
      survey study investigating the impact of education, income, and health behaviors
      on the risk of dying within the next 7.5 years. PARTICIPANTS: A nationally
      representative sample of 3617 adult women and men participating in the Americans'
      Changing Lives survey. MAIN OUTCOME MEASURE: All-cause mortality verified through
      the National Death Index and death certificate reviews. RESULTS: Educational
      differences in mortality were explained in full by the strong association between
      education and income. Controlling for age, sex, race, urbanicity, and education,
      the hazard rate ratio of mortality was 3.22 (95% confidence interval [CI], 2.01
      5.16) for those in the lowest-income group and 2.34 (95% CI, 1.49-3.67) for those
      in the middle-income group. When health risk behaviors were considered, the risk
      of dying was still significantly elevated for the lowest-income group (hazard
      rate ratio, 2.77; 95% CI, 1.74-4.42) and the middle-income group (hazard rate
      ratio, 2.14; 95% CI, 1.38-3.25). CONCLUSION: Although reducing the prevalence of
      health risk behaviors in low-income populations is an important public health
      goal, socioeconomic differences in mortality are due to a wider array of factors
      and, therefore, would persist even with improved health behaviors among the
      disadvantaged.

PMID- 9624023
TI  - Relationship between cancer patients' predictions of prognosis and their
      treatment preferences.
AB  - CONTEXT: Previous studies have documented that cancer patients tend to
      overestimate the probability of long-term survival. If patient preferences about
      the trade-offs between the risks and benefits associated with alternative
      treatment strategies are based on inaccurate perceptions of prognosis, then
      treatment choices may not reflect each patient's true values. OBJECTIVE: To test
      the hypothesis that among terminally ill cancer patients an accurate
      understanding of prognosis is associated with a preference for therapy that
      focuses on comfort over attempts at life extension. DESIGN: Prospective cohort
      study. SETTING: Five teaching hospitals in the United States. PATIENTS: A total
      of 917 adults hospitalized with stage III or IV non-small cell lung cancer or
      colon cancer metastatic to liver in phases 1 and 2 of the Study to Understand
      Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT). MAIN
      OUTCOME MEASURES: Proportion of patients favoring life-extending therapy over
      therapy focusing on relief of pain and discomfort, patient and physician
      estimates of the probability of 6-month survival, and actual 6-month survival.
      RESULTS: Patients who thought they were going to live for at least 6 months were
      more likely (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.8-3.7) to
      favor life-extending therapy over comfort care compared with patients who thought
      there was at least a 10% chance that they would not live 6 months. This OR was
      highest (8.5; 95% CI, 3.0-24.0) among patients who estimated their 6-month
      survival probability at greater than 90% but whose physicians estimated it at 10%
      or less. Patients overestimated their chances of surviving 6 months, while
      physicians estimated prognosis quite accurately. Patients who preferred life
      extending therapy were more likely to undergo aggressive treatment, but
      controlling for known prognostic factors, their 6-month survival was no better.
      CONCLUSIONS: Patients with metastatic colon and lung cancer overestimate their
      survival probabilities and these estimates may influence their preferences about
      medical therapies.

PMID- 9624024
TI  - Cigarette smoking and hearing loss: the epidemiology of hearing loss study.
AB  - CONTEXT: Clinical studies have suggested that cigarette smoking may be associated
      with hearing loss, a common condition affecting older adults. OBJECTIVE: To
      evaluate the association between smoking and hearing loss. DESIGN: Population
      based, cross-sectional study. SETTING: Community of Beaver Dam, Wis.
      PARTICIPANTS: Adults aged 48 to 92 years. Of 4541 eligible subjects, 3753 (83%)
      participated in the hearing study. MAIN OUTCOME MEASURES: The examination
      included otoscopy, screening tympanometry, and pure-tone air-conduction and bone
      conduction audiometry. Smoking history was ascertained by self-report. Hearing
      loss was defined as a pure-tone average (0.5, 1, 2, and 4 kHz) greater than 25-dB
      hearing level in the worse ear. RESULTS: After adjusting for other factors,
      current smokers were 1.69 times as likely to have a hearing loss as nonsmokers
      (95% confidence interval, 1.31-2.17). This relationship remained for those
      without a history of occupational noise exposure and in analyses excluding those
      with non-age-related hearing loss. There was weak evidence of a dose-response
      effect. Nonsmoking participants who lived with a smoker were more likely to have
      a hearing loss than those who were not exposed to a household member who smoked
      (odds ratio, 1.94; 95% confidence interval, 1.01-3.74). CONCLUSIONS: These data
      suggest that environmental exposures may play a role in age-related hearing loss.
      If longitudinal studies confirm these findings, modification of smoking habits
      may prevent or delay age-related declines in hearing sensitivity.

PMID- 9624025
TI  - Depressive symptoms and physical decline in community-dwelling older persons.
AB  - CONTEXT: Significant symptoms of depression are common in the older community
      dwelling population. Although depressive symptoms and disability may commonly
      occur in the same person, whether depressive symptoms contribute to subsequent
      functional decline has not been elucidated. OBJECTIVE: To determine whether
      depressive symptoms in older persons increase the risk of subsequent decline in
      physical function as measured by objective performance-based tests. DESIGN: A 4
      year prospective cohort study. SETTING: The communities of Iowa and Washington
      counties, Iowa. PARTICIPANTS: A total of 1286 persons aged 71 years and older who
      completed a short battery of physical performance tests in 1988 and again 4 years
      later. MAIN OUTCOME MEASURES: Baseline depressive symptoms were assessed by the
      Center for Epidemiological Studies Depression Scale. Physical performance tests
      included an assessment of standing balance, a timed 2.4-m (8-ft) walk, and a
      timed test of 5 repetitions of rising from a chair and sitting down. RESULTS:
      After adjustment for baseline performance score, health status, and
      sociodemographic factors, increasing levels of depressive symptoms were
      predictive of greater decline in physical performance over 4 years (odds ratio
      for decline in those with depressed mood vs those without, 1.55; 95% confidence
      interval [CI], 1.02-2.34). Even among those at the high end of the functional
      spectrum, who reported no disability, the severity of depressive symptoms
      predicted subsequent decline in physical performance (odds ratio for decline,
      1.03; 95% CI, 1.00-1.08). CONCLUSIONS: This study provides evidence that older
      persons who report depressive symptoms are at higher risk of subsequent physical
      decline. These results suggest that prevention or reduction of depressed mood
      could play a role in reducing functional decline in older persons.

PMID- 9624027
TI  - Telomerase and the aging cell: implications for human health.
AB  - Recent research has shown that inserting a gene for the protein component of
      telomerase into senescent human cells reextends their telomeres to lengths
      typical of young cells, and the cells then display all the other identifiable
      characteristics of young, healthy cells. This advance not only suggests that
      telomeres are the central timing mechanism for cellular aging, but also
      demonstrates that such a mechanism can be reset, extending the replicative life
      span of such cells and resulting in markers of gene expression typical of
      "younger" (ie, early passage) cells without the hallmarks of malignant
      transformation. It is now possible to explore the fundamental cellular mechanisms
      underlying human aging, clarifying the role played by replicative senescence. By
      implication, we may soon be able to determine the extent to which the major
      causes of death and disability in aging populations in developed countries
      cancer, atherosclerosis, osteoarthritis, macular degeneration, and Alzheimer
      dementia--are attributable to such fundamental mechanisms. If they are amenable
      to prevention or treatment by alteration of cellular senescence, the clinical
      implications have few historic precedents.

PMID- 9624026
TI  - Adequacy of hospital discharge status as a measure of outcome among injured
      patients.
AB  - CONTEXT: Crude mortality rates at the time of hospital discharge are commonly
      used to assess the quality of care provided to patients hospitalized following
      trauma. OBJECTIVES: To evaluate the adequacy of hospital death rates as an
      outcome measure following trauma and to determine the influence of noninjury
      illness as a cause of hospital death and the frequency of postdischarge death.
      DESIGN: Retrospective cohort analyses using hospital discharge data for injured
      patients cross-linked to death certificate data that provided 1 year of follow-up
      for all patients discharged alive. PATIENTS: A total of 90048 injured patients
      admitted to all acute care hospitals in the state of Washington from 1991 through
      1993 and discharged with at least 1 diagnosis coded in the International
      Classification of Diseases, Ninth Revision, Clinical Modification to indicate
      trauma. MAIN OUTCOME MEASURES: Death in the hospital and death within 30 days of
      hospital discharge. RESULTS: Among 1912 injured patients with in-hospital deaths,
      825 death certificates (43%) listed a noninjury cause of death. The overall
      mortality rate at hospital discharge was 21.2 per 100000 hospitalized injured
      patients, and was 12.1 per 100000 for trauma deaths and 9.1 per 100000 for those
      designated as nontrauma deaths. Patients with trauma-related death designations
      were younger (mean age, 51.5 years vs 77.9 years), had shorter lengths of stay
      (median stay, 2 days vs 5 days), and sustained more severe injures (P<.001).
      Including the 1273 deaths that occurred within 30 days of hospital discharge
      increased rates for trauma-designated deaths to 14.1 per 100000 and increased
      rates for nontrauma-designated deaths to 21.3 per 100000. CONCLUSIONS: Hospital
      discharge death rates are incomplete measures of death frequency for injured
      patients. Designation of the cause of death, especially among older,
      hospitalized, injured patients often reflects preexisting medical conditions.
      Adequate assessment of mortality following trauma requires measurement of the
      frequency of death following hospital discharge.

PMID- 9624028
TI  - Treatment of acute otitis media with a shortened course of antibiotics: a meta
      analysis.
AB  - OBJECTIVE: To conduct a meta-analysis of randomized controlled trials of
      antibiotic treatment of acute otitis media in children to determine whether
      outcomes were comparable in children treated with antibiotics for less than 7
      days or at least 7 days or more. DATA SOURCES: MEDLINE (1966-1997), EMBASE (1974
      1997), Current Contents, and Science Citation Index searches were conducted to
      identify randomized controlled trials of the treatment of acute otitis media in
      children with antibiotics of different durations. STUDY SELECTION: Studies were
      included if they met the following criteria: subjects aged 4 weeks to 18 years,
      clinical diagnosis of acute otitis media, no antimicrobial therapy at time of
      diagnosis, and randomization to less than 7 days of antibiotic treatment vs 7
      days or more of antibiotic treatment. DATA EXTRACTION: Trial methodological
      quality was assessed independently by 7 reviewers; outcomes were extracted as the
      number of treatment failures, relapses, or reinfections. DATA SYNTHESIS: Included
      trials were grouped by antibiotic used in the short course: (1) 15 short-acting
      oral antibiotic trials (penicillin V potassium, amoxicillin [-clavulanate],
      cefaclor, cefixime, cefuroxime, cefpodoxime proxetil, cefprozil), (2) 4
      intramuscularceftriaxone sodium trials, and (3) 11 oral azithromycin trials. The
      summary odds ratio for treatment outcomes at 8 to 19 days in children treated
      with short-acting antibiotics for 5 days vs 8 to 10 days was 1.52 (95% confidence
      interval [CI], 1.17-1.98) but by 20 to 30 days outcomes between treatment groups
      were comparable (odds ratio, 1.22; 95% CI, 0.98 to 1.54). The risk difference
      (2.3%; 95% CI,-0.2% to 4.9%) at 20 to 30 days suggests that 44 children would
      need to be treated with the long course of short-acting antibiotics to avoid 1
      treatment failure. This similarity in later outcomes was observed for up to 3
      months following therapy (odds ratio, 1.16; 95% CI, 0.90-1.50). Comparable
      outcomes were shown between treatment with ceftriaxone or azithromycin, and at
      least 7 days of other antibiotics. CONCLUSION: This meta-analysis suggests that 5
      days of short-acting antibiotic use is effective treatment for uncomplicated
      acute otitis media in children.

PMID- 9624029
TI  - The case for rapid HIV testing during labor.

PMID- 9624030
TI  - Lower socioeconomic status and increased mortality: early childhood roots and the
      potential for successful interventions.

PMID- 9624031
TI  - Telling the truth about terminal cancer.

PMID- 9624032
TI  - Changing the treatment paradigm for acute otitis media in children.

PMID- 9624033
TI  - JAMA patient page: depression.

PMID- 9624034
TI  - The state of the art: how far does it reach?

PMID- 9624035
TI  - On the holistic approach in cellular and cancer biology: nonlinearity,
      complexity, and quasi-determinism of the dynamic cellular network.
AB  - A keystone of the molecular reductionist approach to cellular biology is a
      specific deductive strategy relating genotype to phenotype-two distinct
      categories. This relationship is based on the assumption that the intermediary
      cellular network of actively transcribed genes and their regulatory elements is
      deterministic (i.e., a link between expression of a gene and a phenotypic trait
      can always be identified, and evolution of the network in time is predetermined).
      However, experimental data suggest that the relationship between genotype and
      phenotype is nonbijective (i.e., a gene can contribute to the emergence of more
      than just one phenotypic trait or a phenotypic trait can be determined by
      expression of several genes). This implies nonlinearity (i.e., lack of the
      proportional relationship between input and the outcome), complexity (i.e.
      emergence of the hierarchical network of multiple cross-interacting elements that
      is sensitive to initial conditions, possesses multiple equilibria, organizes
      spontaneously into different morphological patterns, and is controlled in
      dispersed rather than centralized manner), and quasi-determinism (i.e.,
      coexistence of deterministic and nondeterministic events) of the network.
      Nonlinearity within the space of the cellular molecular events underlies the
      existence of a fractal structure within a number of metabolic processes, and
      patterns of tissue growth, which is measured experimentally as a fractal
      dimension. Because of its complexity, the same phenotype can be associated with a
      number of alternative sequences of cellular events. Moreover, the primary cause
      initiating phenotypic evolution of cells such as malignant transformation can be
      favored probabilistically, but not identified unequivocally. Thermodynamic
      fluctuations of energy rather than gene mutations, the material traits of the
      fluctuations alter both the molecular and informational structure of the network.
      Then, the interplay between deterministic chaos, complexity, self-organization,
      and natural selection drives formation of malignant phenotype. This concept
      offers a novel perspective for investigation of tumorigenesis without
      invalidating current molecular findings. The essay integrates the ideas of the
      sciences of complexity in a biological context.

PMID- 9624036
TI  - Pulsing of dendritic cells with cell lysates from either B16 melanoma or MCA-106
      fibrosarcoma yields equally effective vaccines against B16 tumors in mice.
AB  - BACKGROUND AND OBJECTIVES: Dendritic cells (DC) pulsed in vitro with a variety of
      antigens have proved effective in producing specific antitumor effects in vivo.
      Experimental evidence from other laboratories has confirmed that shared antigens
      can be encountered in histologically distinct tumors. In our experiments, we set
      out to evaluate the immunotherapeutic potential of vaccines consisting of DC
      pulsed with MCA-106 fibrosarcoma or B16 melanoma cell lysates and to determine
      whether a cross-reactivity exists between the two tumors. METHODS: DC were
      prepared from the bone marrow of C57BL/6 (B6) mice by culturing progenitor cells
      in murine granulocyte-macrophage colony-stimulating factor (GM-CSF). They were
      separated into three equal groups and were either pulsed with B16 melanoma cell
      lysates (BDC), pulsed with tumor extract from the syngeneic fibrosarcoma MCA-106
      (MDC), or left unpulsed (UDC). DC were then used to immunize three groups of
      mice, with all mice receiving two weekly intravenous (IV) doses of 1 x 10(6) DC
      from their respective preparations on days -14 and -7. A fourth group of control
      mice were left untreated. On day 0, all mice were challenged with subcutaneous
      injections of 1 x 10(5) B16 and 1 x 10(5) MCA tumor cells, administered in the
      left and right thighs, respectively. After the inoculations, the mice were
      monitored closely with respect to tumor growth and survival. RESULTS: The MDC
      mice developed specific cellular immunity directed against not only MCA-106 tumor
      cells, but also against B16 melanoma, as measured through chromium-release assays
      of splenocyte preparations, while remaining ineffective at killing both L929
      fibroblasts and CT26 tumor cells. By day 30 after tumor inoculations, control
      mice manifested the largest B16 tumor volumes at a mean of 2185 mm3, followed by
      the UDC, MDC, and BDC groups at 92 mm3 (P=0.00008), 3 mm3 (P=0.000002), and 2 mm3
      (P=0.00004), respectively. The survival data mirrored this pattern, with control
      animals displaying the shortest mean survival time (37.1+/-4.0 days), followed by
      UDC (44.8+/-6.6), MDC (56.2 +/-14.7), and BDC (56.4+/-18.3) animals. No
      significant differences were noted between MCA-106 and B16 cell lysate-pulsed DC
      vaccines with respect to their abilities to inhibit B16 tumor growth and to
      prolong survival. These findings were confirmed using a B16 pulmonary metastasis
      model. Likewise, vaccination with interferon-gamma gene-modified MCA-106 tumor
      cells was shown to be effective at protecting against a subsequent subcutaneous
      B16 tumor challenge in 3 of 4 mice observed. CONCLUSIONS: These results
      demonstrate that immunization with antigen-pulsed DC confers cellular immunity,
      retards tumor growth, and prolongs the survival of tumor-challenged mice. The
      ability of MCA-106 cell lysate-pulsed DC vaccines to inhibit the growth of
      subcutaneous B16 tumors also suggests the presence of shared tumor-associated
      antigens between these two histologically distinct tumors.

PMID- 9624037
TI  - Level of alpha-catenin expression in colorectal cancer correlates with
      invasiveness, metastatic potential, and survival.
AB  - BACKGROUND AND OBJECTIVES: Decreased expression of the E-cadherin/alpha-catenin
      cell-cell adhesion complex is considered to elicit detachment of tumor cells from
      primary lesions and development of metastases. The immunohistochemical profile of
      alpha-catenin in colorectal cancer, as well as its correlation with
      differentiation, lymph node/liver metastasis and patient survival is presented in
      this study. METHODS: Alpha-Catenin expression was investigated with
      immunohistochemistry technique, in 85 paraffin-embedded and 21 fresh frozen
      specimens, including 82 colon adenocarcinomas, 10 adenomas, 10 lymph nodes, and 3
      liver metastases. Preserved alpha-catenin expression was considered for those
      tumors that demonstrated more than 90% alpha-catenin(+) cancer cells and reduced
      alpha-catenin expression for those tumors with less than 90% alpha-catenin(+)
      cancer cells. The chi2-test was used to calculate the statistical correlation of
      alpha-catenin expression with grade of differentiation and metastatic potential
      and the log-rank test for the correlation with survival rate. RESULTS: Normal
      mucosa, as well as 8/10 of the colon adenomas, showed strong membranous alpha
      catenin expression. Reduced alpha-catenin expression was found in 32/82 (39%)
      colorectal cancers examined, which was associated with de-differentiation (P <
      0.01), lymph node metastasis (P < 0.025), and poor clinical outcome (P < 0.012).
      Alpha-Catenin expression was preserved in 3 liver metastases and their
      corresponding primary tumors. By contrast, 6/10 of lymphogenous metastases showed
      decreased alpha-catenin expression. CONCLUSIONS: Our findings demonstrate a
      significant down-regulation of alpha-catenin expression in colorectal cancer
      which is associated with poor differentiation, higher metastatic potential and
      unfavorable prognosis. These preliminary results suggest that alpha-catenin may
      be a useful marker of invasiveness, metastatic potential, and survival in
      colorectal cancer patients.

PMID- 9624038
TI  - Giant cell tumor of the tendon sheath: a retrospective study of 28 cases.
AB  - BACKGROUND AND OBJECTIVES: Giant cell tumor of the tendon sheath (GCTTS) is a
      lesion of uncertain etiology. To better interpret pathogenesis and aid in the
      differentiation of GCTTS from other similar pathological processes we reviewed
      the literature and analyzed the available information. METHODS: We
      retrospectively studied clinicopathologic findings in 28 cases of GCTTS on the
      basis of anatomic location and histologic appearance of the lesion. RESULTS: The
      GCTTS could be divided into those involving the common digits (20 cases) and
      larger joint group (8 cases) based on anatomic location. Grossly the digit tumors
      were small, multiple, surrounded by a thin fibrous capsule, and had a variegated
      appearance, while the large joint tumors were relatively large and covered by one
      or more layers of synovium. Microscopically both groups consisted of a mixture of
      round to polygonal histiocytes, foam cells, hemosiderin laden macrophages, and
      multinucleated giant cells. The giant cells seemed more abundant in the digit
      tumors, while the pseudoglandular spaces lined by synovial cells were more
      striking in the large joint group. CONCLUSIONS: Local excision was the treatment
      of choice in the majority of the patients. Eight patients had local recurrence.

PMID- 9624039
TI  - Hepatic cryosurgery for recurrent hepatocellular carcinoma after hepatectomy: a
      preliminary report.
AB  - BACKGROUND AND OBJECTIVES: The treatment of choice for recurrent hepatocellular
      carcinoma (HCC) is repeated resection. However, only a small percentage of
      patients are suitable for further hepatic resection. The aim of this study was to
      evaluate the surgical risk and operative outcome of hepatic cryosurgery in
      patients with recurrent HCC. METHODS: A retrospective analysis of patients with
      recurrent HCC after previous curative hepatectomy treated with cryosurgery. Four
      patients with recurrent HCC not suitable for further resection were enrolled for
      cryosurgery, their clinical parameters, the operative details and outcome were
      studied. RESULTS: No intraoperative or postoperative complications were noted.
      The duration of operation ranged from 3-5.2 hr and the operative blood loss from
      173-1,300 ml. All patients are still alive with survival after cryosurgery
      ranging from 12-23 mo (25-63 mo after the hepatic resection). Three patients
      showed evidence of recurrent disease and one patient was disease free.
      CONCLUSIONS: Hepatic cryosurgery is a safe therapy for patients with unresectable
      recurrent HCC.

PMID- 9624040
TI  - Tenascin pattern of expression and established prognostic factors in invasive
      breast carcinoma.
AB  - BACKGROUND AND OBJECTIVES: Immunohistochemical methods were used to study
      Tenascin (TN) expression in invasive duct cell carcinoma (IDCC) of the breast and
      its established prognostic factors. METHODS: We studied 115 patients with IDCC.
      The mean patient age was 62 years; all tumors were graded according to Scarf
      Bloom and Richardson. Complete survival information was available for all
      patients (median follow-up 65 months). Formalin-fixed, paraffin-embedded archival
      tissue from all 115 IDCC were immunostained with monoclonal mouse Anti-Human
      Tenascin (DAKO-TN2M636; 1/50 dilution). Positivity was recorded on a scale of 0-4
      for percentage of TN staining in the tumor stroma. RESULTS: TN showed thick bands
      around advancing tumor nests and in poorly differentiated tumors, TN fibers had
      an interstitial pattern surrounding single tumor cells. TN score was
      significantly positively correlated with high nuclear grade (P < 0.05),
      histologic grade (P < 0.01), mitotic grade (P < 0.005), and combined grade (P <
      0.01). TN score did not correlate with long-term survival or with other
      prognostic factors studied. CONCLUSIONS: TN expression was more prominent in
      tumors with a high combined histologic grade. Our results may suggest that while
      TN may play a role in limiting tumor spread as proposed by other studies, it may
      not represent a prognostic factor in invasive breast carcinoma.

PMID- 9624041
TI  - Renal carcinoid and horseshoe kidney: a frequent association of two rare entities
      -a case report and review of the literature.
AB  - We report the case of a primary renal carcinoid tumor associated with a horseshoe
      malformation in a 43-year-old man who presented with testicular pain. The tumor
      was centrally located and purely solid and had features ascribed to hindgut
      neuroendocrine neoplasia. The relative risk of developing a carcinoid tumor in a
      horseshoe kidney is estimated to be x82.

PMID- 9624042
TI  - Choledochojejunostomy with invagination of the bile duct into the jejunum.

PMID- 9624043
TI  - Use of cellular and cytokine adjuvants in the immunotherapy of cancer.
AB  - Cellular and cytokine adjuvants, often immune effector cells and soluble factors,
      respectively, are supplemental and/or follow-up treatments of human origin for
      cancer patients who have unsatisfactory clinical responses to conventional
      chemotherapy, radiotherapy, and surgery. Since many human studies with these
      reagents are in their infancy, extensive data collection is only now being
      performed to determine which strategy provides the greatest therapeutic benefit.
      Research published in the literature since the genesis of this approach to cancer
      treatment is summarized in this report. Methodologies attempting to generate
      anticancer responses by provoking or enhancing the patient's own immune system
      are new compared with the other standard types of cancer treatment. Although a
      few encouraging human studies can be discussed, many of the most promising
      techniques are only now being transferred from the laboratory to the clinic. The
      administration of immune effector cells in combination with immunomodulators,
      such as interferons or interleukins, often enhances clinical outcome. The
      literature cited in this report indicate that immune-cell- and cytokine-based
      therapies hold promise in our attempts to improve the quality and duration of
      life in those with cancer. With each report reaching the literature, more
      effective clinical trials are being designed and implemented.

PMID- 9624044
TI  - Redox-coupled crystal structural changes in bovine heart cytochrome c oxidase.
AB  - Crystal structures of bovine heart cytochrome c oxidase in the fully oxidized,
      fully reduced, azide-bound, and carbon monoxide-bound states were determined at
      2.30, 2.35, 2.9, and 2.8 angstrom resolution, respectively. An aspartate residue
      apart from the O2 reduction site exchanges its effective accessibility to the
      matrix aqueous phase for one to the cytosolic phase concomitantly with a
      significant decrease in the pK of its carboxyl group, on reduction of the metal
      sites. The movement indicates the aspartate as the proton pumping site. A
      tyrosine acidified by a covalently linked imidazole nitrogen is a possible proton
      donor for the O2 reduction by the enzyme.

PMID- 9624045
TI  - Endocranial capacity in an early hominid cranium from Sterkfontein, South Africa.
AB  - Two- and three-dimensional computer imaging shows that endocranial capacity in an
      approximately 2.8- to 2.6-million-year-old early hominid cranium (Stw 505) from
      Sterkfontein, South Africa, tentatively assigned to Australopithecus africanus,
      is approximately 515 cubic centimeters. Although this is the largest endocranial
      capacity recorded for this species, it is still markedly less than anecdotal
      reports of endocranial capacity exceeding 600 cubic centimeters. No
      australopithecine has an endocranial capacity approaching, let alone exceeding,
      600 cubic centimeters. Some currently accepted estimates of early hominid
      endocranial capacity may be inflated, suggesting that the tempo and mode of early
      hominid brain evolution may need reevaluation.

PMID- 9624046
TI  - Single-molecule vibrational spectroscopy and microscopy 
AB  - Vibrational spectra for a single molecule adsorbed on a solid surface have been
      obtained with a scanning tunneling microscope (STM). Inelastic electron tunneling
      spectra for an isolated acetylene (C2H2) molecule adsorbed on the copper (100)
      surface showed an increase in the tunneling conductance at 358 millivolts,
      resulting from excitation of the C-H stretch mode. An isotopic shift to 266
      millivolts was observed for deuterated acetylene (C2D2). Vibrational microscopy
      from spatial imaging of the inelastic tunneling channels yielded additional data
      to further distinguish and characterize the two isotopes. Single-molecule
      vibrational analysis should lead to better understanding and control of surface
      chemistry at the atomic level.

PMID- 9624047
TI  - Combinatorial electrochemistry: A highly parallel, optical screening method for
      discovery of better electrocatalysts 
AB  - Combinatorial screening of electrochemical catalysts by current-voltage methods
      can be unwieldy for large sample sizes. By converting the ions generated in an
      electrochemical half-cell reaction to a fluorescence signal, the most active
      compositions in a large electrode array have been identified. A fluorescent acid
      base indicator was used to image high concentrations of hydrogen ions, which were
      generated in the electrooxidation of methanol. A 645-member electrode array
      containing five elements (platinum, ruthenium, osmium, iridium, and rhodium), 80
      binary, 280 ternary, and 280 quaternary combinations was screened to identify the
      most active regions of phase space. Subsequent "zoom" screens pinpointed several
      very active compositions, some in ternary and quaternary regions that were
      bounded by rather inactive binaries. The best catalyst,
      platinum(44)/ruthenium(41)/osmium(10)/iridium(5) (numbers in parentheses are
      atomic percent), was significantly more active than platinum(50)/ruthenium(50) in
      a direct methanol fuel cell operating at 60 degreesC, even though the latter
      catalyst had about twice the surface area of the former.

PMID- 9624048
TI  - Compatibility of rhenium in garnet during mantle melting and magma genesis 
AB  - Measurements of the partitioning of rhenium (Re) between garnet and silicate
      liquid from 1.5 to 2.0 gigapascals and 1250 degrees to 1350 degreesC show that Re
      is compatible in garnet. Oceanic island basalts (OIBs) have lower Re contents
      than mid-ocean ridge basalt, because garnet-bearing residues of deeper OIB
      melting will retain Re. Deep-mantle garnetite or eclogite may harbor the missing
      Re identified in crust-mantle mass balance calculations. Oceanic crust recycled
      into the upper mantle at subduction zones will retain high Re/Os (osmium) ratios
      and become enriched in radiogenic 187Os. Recycled eclogite in a mantle source
      should be easily traced using Re abundances and Os isotopes.

PMID- 9624049
TI  - Integrated optoelectronic devices based on conjugated polymers 
AB  - An all-polymer semiconductor integrated device is demonstrated with a high
      mobility conjugated polymer field-effect transistor (FET) driving a polymer light
      emitting diode (LED) of similar size. The FET uses regioregular
      poly(hexylthiophene). Its performance approaches that of inorganic amorphous
      silicon FETs, with field-effect mobilities of 0.05 to 0.1 square centimeters per
      volt second and ON-OFF current ratios of >10(6). The high mobility is attributed
      to the formation of extended polaron states as a result of local self
      organization, in contrast to the variable-range hopping of self-localized
      polarons found in more disordered polymers. The FET-LED device represents a step
      toward all-polymer optoelectronic integrated circuits such as active-matrix
      polymer LED displays.

PMID- 9624050
TI  - Carbon nanotube quantum resistors 
AB  - The conductance of multiwalled carbon nanotubes (MWNTs) was found to be
      quantized. The experimental method involved measuring the conductance of
      nanotubes by replacing the tip of a scanning probe microscope with a nanotube
      fiber, which could be lowered into a liquid metal to establish a gentle
      electrical contact with a nanotube at the tip of the fiber. The conductance of
      arc-produced MWNTs is one unit of the conductance quantum G0 = 2e2/h = (12.9
      kilohms)-1. The nanotubes conduct current ballistically and do not dissipate
      heat. The nanotubes, which are typically 15 nanometers wide and 4 micrometers
      long, are several orders of magnitude greater in size and stability than other
      typical room-temperature quantum conductors. Extremely high stable current
      densities, J > 10(7) amperes per square centimeter, have been attained.

PMID- 9624051
TI  - Hormone-dependent coactivator binding to a hydrophobic cleft on nuclear
      receptors.
AB  - The ligand-binding domain of nuclear receptors contains a transcriptional
      activation function (AF-2) that mediates hormone-dependent binding of coactivator
      proteins. Scanning surface mutagenesis on the human thyroid hormone receptor was
      performed to define the site that binds the coactivators, glucocorticoid receptor
      interacting protein 1 (GRIP1) and steroid receptor coactivator 1 (SRC-1). The
      residues involved encircle a small surface that contains a hydrophobic cleft.
      Ligand activation of transcription involves formation of this surface by folding
      the carboxyl-terminal alpha helix against a scaffold of three other helices.
      These features may represent general ones for nuclear receptors.

PMID- 9624052
TI  - Mutation of BCL-6 gene in normal B cells by the process of somatic hypermutation
      of Ig genes.
AB  - Immunoglobulin (Ig) genes are hypermutated in B lymphocytes that are the
      precursors to memory B cells. The mutations are linked to transcription
      initiation, but non-Ig promoters are permissible for the mutation process; thus,
      other genes expressed in mutating B cells may also be subject to somatic
      hypermutation. Significant mutations were not observed in c-MYC, S14, or alpha
      fetoprotein (AFP) genes, but BCL-6 was highly mutated in a large proportion of
      memory B cells of normal individuals. The mutation pattern was similar to that of
      Ig genes.

PMID- 9624053
TI  - Mutation of a gene encoding a protein with extracellular matrix motifs in Usher
      syndrome type IIa.
AB  - Usher syndrome type IIa (OMIM 276901), an autosomal recessive disorder
      characterized by moderate to severe sensorineural hearing loss and progressive
      retinitis pigmentosa, maps to the long arm of human chromosome 1q41 between
      markers AFM268ZD1 and AFM144XF2. Three biologically important mutations in Usher
      syndrome type IIa patients were identified in a gene (USH2A) isolated from this
      critical region. The USH2A gene encodes a protein with a predicted size of 171.5
      kilodaltons that has laminin epidermal growth factor and fibronectin type III
      motifs; these motifs are most commonly observed in proteins comprising components
      of the basal lamina and extracellular matrixes and in cell adhesion molecules.

PMID- 9624054
TI  - Promotion of met-tRNAiMet binding to ribosomes by yIF2, a bacterial IF2 homolog
      in yeast.
AB  - Delivery of the initiator methionine transfer RNA (Met-tRNAiMet) to the ribosome
      is a key step in the initiation of protein synthesis. Previous results have
      indicated that this step is catalyzed by the structurally dissimilar translation
      factors in prokaryotes and eukaryotes-initiation factor 2 (IF2) and eukaryotic
      initiation factor 2 (eIF2), respectively. A bacterial IF2 homolog has been
      identified in both eukaryotes and archaea. By using a combination of molecular
      genetic and biochemical studies, the Saccharomyces cerevisiae IF2 homolog is
      shown to function in general translation initiation by promoting Met-tRNAiMet
      binding to ribosomes. Thus, the mechanism of protein synthesis in eukaryotes and
      prokaryotes is more similar than was previously realized.

PMID- 9624055
TI  - The ubiquitin-related protein RUB1 and auxin response in Arabidopsis.
AB  - The AXR1 (auxin-resistant) protein, which has features of the ubiquitin
      activating enzyme E1, is required for normal response to the plant hormone auxin
      in Arabidopsis thaliana. ECR1 functions together with AXR1 to activate members of
      the RUB/NEDD8 family of ubiquitin-related proteins. Extracts from mutant
      seedlings lacking AXR1 did not promote formation of the RUB-ECR1 thiolester,
      indicating that AXR1 is the major activity in this tissue. AXR1 was localized
      primarily to the nucleus of dividing and elongating cells, suggesting that the
      targets of RUB modification are nuclear. These results indicate that auxin
      response depends on RUB modification of one or more nuclear proteins.

PMID- 9624056
TI  - Close contacts with the endoplasmic reticulum as determinants of mitochondrial
      Ca2+ responses.
AB  - The spatial relation between mitochondria and endoplasmic reticulum (ER) in
      living HeLa cells was analyzed at high resolution in three dimensions with two
      differently colored, specifically targeted green fluorescent proteins. Numerous
      close contacts were observed between these organelles, and mitochondria in situ
      formed a largely interconnected, dynamic network. A Ca2+-sensitive photoprotein
      targeted to the outer face of the inner mitochondrial membrane showed that, upon
      opening of the inositol 1,4,5-triphosphate (IP3)-gated channels of the ER, the
      mitochondrial surface was exposed to a higher concentration of Ca2+ than was the
      bulk cytosol. These results emphasize the importance of cell architecture and the
      distribution of organelles in regulation of Ca2+ signaling.

PMID- 9624057
TI  - Public confidence and cardiac surgical outcome. Cardiac surgery: the fall guy in
      medical quality assurance.

PMID- 9624058
TI  - Hospital at home: from red to amber?. Data that will reassure advocates-but
      without satisfying the sceptics.

PMID- 9624059
TI  - Can an economic case be made for investing in health?. No, but it's the wrong
      question.

PMID- 9624060
TI  - Ethnicity, social inequality, and mental illness. In a community setting the
      picture is complex.

PMID- 9624061
TI  - Targeting subclinical atherosclerosis. Has the potential to reduce coronary
      events dramatically.

PMID- 9624062
TI  - Clinical outcome in relation to care in centres specialising in cystic fibrosis:
      cross sectional study.
AB  - OBJECTIVES: To assess the effect on clinical outcome of managing paediatric and
      adult patients with cystic fibrosis at specialised cystic fibrosis centres.
      DESIGN: Cross sectional study. SETTING: Two adult cystic fibrosis centres in the
      United Kingdom. SUBJECTS: Patients from an adult cystic fibrosis centre in
      Manchester were subdivided into those who had received continuous care from
      paediatric and adult cystic fibrosis centres (group A), and those who had
      received paediatric care in a centre not specialising in cystic fibrosis followed
      by adult care in a cystic fibrosis centre (group B). Group C were referrals to
      the new adult cystic fibrosis centre in Cambridge who had received neither
      paediatric nor adult centre care for their cystic fibrosis. MAIN OUTCOME
      MEASURES: Body mass index (weight (kg)/height (m2)), lung function (forced
      expiratory volume in one second (FEV1 percentage of predicted)), the Northern
      chest x ray film score, and age at colonisation with Pseudomonas aeruginosa.
      RESULTS: A prominent stepwise increase in body mass index was associated with
      increasing amounts of care at a cystic fibrosis centre; 18.3, 20.2, and 21.3 for
      groups C, B, and A respectively (P<0.001). Improved nutritional status was
      correlated with a higher FEV1 and better (lower) chest x ray film scores; r=0. 52
      and -0.45 respectively (P<0.001 for both). CONCLUSION: These findings provide the
      first direct evidence that management of cystic fibrosis in paediatric and adult
      cystic fibrosis centres results in a better clinical outcome, and strongly
      supports the provision of these specialist services.

PMID- 9624063
TI  - Screening for chlamydial infections and the risk of ectopic pregnancy in a county
      in Sweden: ecological analysis.
AB  - OBJECTIVES: To analyse trends in rates of genital chlamydial infection and
      ectopic pregnancy between 1985 and 1995 in a county in Sweden. SETTING: Uppsala
      county where screening for chlamydial infection, treatment, and contact tracing
      has been widespread and where ectopic pregnancies are recorded. METHODS: Rates of
      chlamydial infections and ectopic pregnancy between 1985 and 1995 were calculated
      for women aged 20-39 years. Poisson and linear regression were used to examine
      the association between the risk of ectopic pregnancy and the current rates of
      chlamydial infection and rates of chlamydial infection from up to 5 years
      earlier. MAIN OUTCOME MEASURES: Rates of chlamydial infection per 100
      examinations, rates of ectopic pregnancy per 1000 pregnancies, rate ratios and
      95% confidence intervals for an increase in chlamydial infections of 5 new cases
      per 100 examinations. RESULTS: 103 870 cervical samples from women aged 15-39
      years were analysed; 5648 (5.4%) were positive for chlamydia. 51 630 pregnancies
      were analysed; 930 (1.8%) were ectopic. Both rates declined over time. For women
      aged 20-24 years there was a strong correlation between the rate of ectopic
      pregnancy and the rate of chlamydial infection in the same year (r=0.93, P<0.
      001); among older women correlations were stronger with rates of chlamydial
      infection occurring 1 or 2 years earlier. In Poisson regression ectopic pregnancy
      was most strongly associated with the current rate of chlamydial infection among
      women aged 20-24 (rate ratio 1.85, 95% confidence interval 1.44 to 2.38), with
      the rate of infection 1 year earlier among 25-29 year olds (rate ratio 1.72, 1.
      33 to 2.22) and 30-34 year olds (rate ratio 2.27, 1.53 to 3.37); and with the
      rate 2 years earlier among 35 to 39 year olds (rate ratio 2. 58, 1.45 to 4.60).
      CONCLUSIONS: Declining rates of genital chlamydial infections have probably led
      to a fall in the rate of ectopic pregnancies. The timing of the decline in the
      rate of ectopic pregnancies varies with age. Among young women falling rates of
      chlamydial infection have been accompanied by an immediate reduction in the rate
      of ectopic pregnancy.

PMID- 9624064
TI  - Blood pressure and mortality in elderly people aged 85 and older: community based
      study.
AB  - OBJECTIVE: To determine whether the inverse relation between blood pressure and
      all cause mortality in elderly people over 85 years of age can be explained by
      adjusting for health status, and to determine whether high blood pressure is a
      risk factor for mortality when the effects of poor health are accounted for.
      DESIGN: 5 to 7 year follow up of community residents aged 85 years and older.
      SETTING: Leiden, the Netherlands. SUBJECTS: 835 subjects whose blood pressure was
      recorded between 1987 and 1989. MAIN OUTCOME MEASURE: All cause mortality.
      RESULTS: An inverse relation between blood pressure and all cause mortality was
      observed. For diastolic blood pressure crude 5 year all cause mortality decreased
      from 88% (52/59) (95% confidence interval 79% to 95%) in those with diastolic
      blood pressures <65 mm Hg to 59% (27/46) (44% to 72%) in those with diastolic
      pressures >100 mm Hg. For systolic blood pressure crude 5 year all cause
      mortality decreased from 85% (95/112) (78% to 91%) in those with systolic
      pressures <125 mm Hg to 59% (13/22) (38% to 78%) in those with systolic pressures
      >200 mm Hg. This decrease was no longer significant after adjustment for
      indicators of poor health. No relation existed between blood pressure and
      mortality from cardiovascular causes or stroke after adjustment for age and sex,
      but after adjustment for age, sex, and indicators of poor health there was a
      positive relation between diastolic blood pressure and mortality from both
      cardiovascular causes and stroke. CONCLUSION: The inverse relation between blood
      pressure and all cause mortality in elderly people over 85 is associated with
      health status.

PMID- 9624066
TI  - An expedition without medical aid 

PMID- 9624065
TI  - Lone atrial fibrillation in vigorously exercising middle aged men: case-control
      study.

PMID- 9624067
TI  - Down but not out 

PMID- 9624068
TI  - Randomised controlled trial comparing hospital at home care with inpatient
      hospital care. I: three month follow up of health outcomes.
AB  - OBJECTIVES: To compare hospital at home care with inpatient hospital care in
      terms of patient outcomes. DESIGN: Randomised controlled trial with three month
      follow up. SETTING: District general hospital and catchment area of neighbouring
      community trust. SUBJECTS: Patients recovering from hip replacement (n=86), knee
      replacement (n=86), and hysterectomy (n=238); elderly medical patients (n=96);
      and patients with chronic obstructive airways disease (n=32). INTERVENTIONS:
      Hospital at home care or inpatient hospital care. MAIN OUTCOME MEASURES:
      Dartmouth COOP chart to measure patients' general health status; SF-36 to measure
      possible limitations in physical functioning of patients with hysterectomy;
      disease specific measures-chronic respiratory disease questionnaire, Barthel
      index for elderly medical patients, Oxford hip score, and Bristol knee score;
      hospital readmission and mortality data; carer strain index to measure burden on
      carers; patients' and carers' preferred form of care. RESULTS: At follow up,
      there were no major differences in outcome between hospital at home care and
      hospital care for any of the patient groups except that those recovering from hip
      replacement reported a significantly greater improvement in quality of life with
      hospital at home care (difference in change from baseline value 0.50, 95%
      confidence interval 0.13 to 0.88). Hospital at home did not seem suitable for
      patients recovering from a knee replacement, as 14 (30%) of patients allocated to
      hospital at home remained in hospital. Patients in all groups preferred hospital
      at home care except those with chronic obstructive airways disease. No
      differences were detected for carer burden. Carers of patients recovering from
      knee replacement preferred hospital at home care, while carers of patients
      recovering from a hysterectomy preferred hospital care. CONCLUSIONS: Few
      differences in outcome were detected. Thus, the cost of hospital at home compared
      with hospital care becomes a primary concern.

PMID- 9624069
TI  - Randomised controlled trial comparing hospital at home care with inpatient
      hospital care. II: cost minimisation analysis.
AB  - OBJECTIVES: To examine the cost of providing hospital at home in place of some
      forms of inpatient hospital care. DESIGN: Cost minimisation study within a
      randomised controlled trial. SETTING: District general hospital and catchment
      area of neighbouring community trust. SUBJECTS: Patients recovering from hip
      replacement (n=86), knee replacement (n=86), and hysterectomy (n=238); elderly
      medical patients (n=96); and patients with chronic obstructive airways disease
      (n=32). INTERVENTIONS: Hospital at home or inpatient hospital care. MAIN OUTCOME
      MEASURES: Cost of hospital at home scheme to health service, to general
      practitioners, and to patients and their families compared with hospital care.
      RESULTS: No difference was detected in total healthcare costs between hospital at
      home and hospital care for patients recovering from a hip or knee replacement, or
      elderly medical patients. Hospital at home significantly increased healthcare
      costs for patients recovering from a hysterectomy (ratio of geometrical means
      1.15, 95% confidence interval 1.04 to 1.29, P=0.009) and for those with chronic
      obstructive airways disease (Mann-Whitney U test, P=0.01). Hospital at home
      significantly increased general practitioners' costs for elderly medical patients
      (Mann-Whitney U test, P<0.01) and for those with chronic obstructive airways
      disease (P=0.02). Patient and carer expenditure made up a small proportion of
      total costs. CONCLUSION: Hospital at home care did not reduce total healthcare
      costs for the conditions studied in this trial, and costs were significantly
      increased for patients recovering from a hysterectomy and those with chronic
      obstructive airways disease. There was some evidence that costs were shifted to
      primary care for elderly medical patients and those with chronic obstructive
      airways disease.

PMID- 9624071
TI  - Known by name 

PMID- 9624070
TI  - Randomised controlled trial comparing effectiveness and acceptability of an early
      discharge, hospital at home scheme with acute hospital care.
AB  - OBJECTIVE: To compare effectiveness and acceptability of early discharge to a
      hospital at home scheme with that of routine discharge from acute hospital.
      DESIGN: Pragmatic randomised controlled trial. SETTING: Acute hospital wards and
      community in north of Bristol, with a catchment population of about 224 000
      people. SUBJECTS: 241 hospitalised but medically stable elderly patients who
      fulfilled criteria for early discharge to hospital at home scheme and who
      consented to participate. INTERVENTIONS: Patients' received hospital at home care
      or routine hospital care. MAIN OUTCOME MEASURES: Patients' quality of life,
      satisfaction, and physical functioning assessed at 4 weeks and 3 months after
      randomisation to treatment; length of stay in hospital and in hospital at home
      scheme after randomisation; mortality at 3 months. RESULTS: There were no
      significant differences in patient mortality, quality of life, and physical
      functioning between the two arms of the trial at 4 weeks or 3 months. Only one of
      11 measures of patient satisfaction was significantly different: hospital at home
      patients perceived higher levels of involvement in decisions. Length of stay for
      those receiving routine hospital care was 62% (95% confidence interval 51% to
      75%) of length of stay in hospital at home scheme. CONCLUSIONS: The early
      discharge hospital at home scheme was similar to routine hospital discharge in
      terms of effectiveness and acceptability. Increased length of stay associated
      with the scheme must be interpreted with caution because of different
      organisational characteristics of the services.

PMID- 9624072
TI  - Alternative definitions 

PMID- 9624073
TI  - Long term influence of diet in pregnancy 

PMID- 9624075
TI  - Primary care: core values. Core values in a changing world.

PMID- 9624074
TI  - Hospital at home or acute hospital care? A cost minimisation analysis.
AB  - OBJECTIVE: To compare, from the viewpoints of the NHS and social services and of
      patients, the costs associated with early discharge to a hospital at home scheme
      and those associated with continued care in an acute hospital. DESIGN: Cost
      minimisation analysis. SETTING: Acute hospital wards and the community in the
      north of Bristol (population about 224 000). SUBJECTS: 241 hospitalised but
      medically stable elderly patients who fulfilled the criteria for early discharge
      to a hospital at home scheme and who consented to participate. MAIN OUTCOME
      MEASURES: Costs to the NHS, social services, and patients over the 3 months after
      randomisation. RESULTS: The mean cost for hospital at home patients over the 3
      months was 2516 pounds, whereas that for hospital patients was 3292 pounds. Under
      all the assumptions used in the sensitivity analysis, the cost of hospital at
      home care was less than that of hospital care. Only when hospital costs were
      assumed to be less than 50% of those used in the initial analysis was the
      difference equivocal. CONCLUSIONS: The hospital at home scheme is less costly
      than care in the acute hospital. These results may be generalisable to schemes of
      similar size and scope, operating in a similar context of rising acute
      admissions.

PMID- 9624077
TI  - Could boxing be banned? A legal and epidemiological perspective.

PMID- 9624076
TI  - Rheumatology.

PMID- 9624078
TI  - A patient led NHS: managing demand at the interface between lay and primary care.

PMID- 9624079
TI  - Assessing health needs in developing countries.

PMID- 9624080
TI  - MMR vaccination and autism 1998. There is no causal link between MMR vaccine and
      autism.

PMID- 9624081
TI  - The health of Gypsies. Problem of caring for travellers is British, not just
      European.

PMID- 9624082
TI  - Citalopram is safe.

PMID- 9624083
TI  - Removing intravascular lines at 72 hours allows need for antibiotics to be
      reassessed.

PMID- 9624084
TI  - Exceptionalism in HIV. Challenge for Africa too.

PMID- 9624085
TI  - CAGE questionnaire allows doctors to avoid focusing on specifics of drinking.

PMID- 9624086
TI  - Audit commission tackles anaesthetic services. Anaesthesia should remain
      physician based service.

PMID- 9624087
TI  - Experience is paramount for successful management of disease.

PMID- 9624088
TI  - Urgency and priority models. Model has limited practical application.

PMID- 9624089
TI  - Clinical and economic arguments favour extension to upper age limit for breast
      screening.

PMID- 9624090
TI  - Gamete donors for IVF should relinquish right of ownership to resulting embryos.

PMID- 9624091
TI  - Water fluoridation is safe and effective.

PMID- 9624092
TI  - Filters inserted into the vena cava may be useful for some indications.

PMID- 9624093
TI  - Providing letters to patients. Patients find summary letters useful.

PMID- 9624095
TI  - Charles douglas anderson 

PMID- 9624094
TI  - Cover picture meant that BMJ had descended to level of tabloid newspapers 

PMID- 9624096
TI  - Medical academic staffs conference 

PMID- 9624097
TI  - Dead hospitals 

PMID- 9624098
TI  - Why I practise in montpelier 

PMID- 9624099
TI  - Parenting is not on the medical curriculum 

PMID- 9624101
TI  - Genetics: society and clinical practice 

PMID- 9624100
TI  - Palliative care ethics: A good companion 

PMID- 9624102
TI  - Centre care of cystic fibrosis improves clinical outcome 

PMID- 9624103
TI  - Chlamydia screening in sweden reduces the risk of ectopic pregnancy 

PMID- 9624104
TI  - High blood pressure associated with longer life among elderly people 

PMID- 9624105
TI  - Lone atrial fibrillation is commoner in middle aged men who exercise vigorously 

PMID- 9624106
TI  - Hospital at home is effective and acceptable but it's not clear whether it is
      cheaper 

PMID- 9624107
TI  - Amyloid precursor protein processing in sterol regulatory element-binding protein
      site 2 protease-deficient Chinese hamster ovary cells.
AB  - Amyloid peptides of 39-43 amino acids (Abeta) are the major constituents of
      amyloid plaques present in the brains of Alzheimer's (AD) patients. Proteolytic
      processing of the amyloid precursor protein (APP) by the yet unidentified beta-
      and gamma-secretases leads to the generation of the amyloidogenic Abeta peptides.
      Recent data suggest that all of the known mutations leading to early onset
      familial AD alter the processing of APP such that increased amounts of the 42
      amino acid form of Abeta are generated by a gamma-secretase activity.
      Identification of the beta- and/or gamma-secretases is a major goal of current AD
      research, as they are prime targets for therapeutic intervention in AD. It has
      been suggested that the sterol regulatory element-binding protein site 2 protease
      (S2P) may be identical to the long sought gamma-secretase. We have directly
      tested this hypothesis using over-expression of the S2P cDNA in cells expressing
      APP and by characterizing APP processing in mutant Chinese hamster ovary cells
      that are deficient in S2P activity and expression. The data demonstrate that S2P
      does not play an essential role in the generation or secretion of Abeta peptides
      from cells, thus it is unlikely to be a gamma-secretase.

PMID- 9624108
TI  - Agmatine suppresses proliferation by frameshift induction of antizyme and
      attenuation of cellular polyamine levels.
AB  - Polyamines are required for entry and progression of the cell cycle. As such,
      augmentation of polyamine levels is essential for cellular transformation.
      Polyamines are autoregulated through induction of antizyme, which represses both
      the rate-limiting polyamine biosynthetic enzyme ornithine decarboxylase and
      cellular polyamine transport. In the present study we demonstrate that agmatine,
      a metabolite of arginine via arginine decarboxylase (an arginine pathway distinct
      from that of the classical polyamines), also serves the dual regulatory functions
      of suppressing polyamine biosynthesis and cellular polyamine uptake through
      induction of antizyme. The capacity of agmatine to induce antizyme is
      demonstrated by: (a) an agmatine-dependent translational frameshift of antizyme
      mRNA to produce a full-length protein and (b) suppression of agmatine-dependent
      inhibitory activity by either anti-antizyme IgG or antizyme inhibitor.
      Furthermore, agmatine administration depletes intracellular polyamine levels to
      suppress cellular proliferation in a transformed cell line. This suppression is
      reversible with polyamine supplementation. We propose a novel regulatory pathway
      in which agmatine acts as an antiproliferative molecule and potential tumor
      suppressor by restricting the cellular polyamine supply required to support
      growth.

PMID- 9624109
TI  - A reporter mutation approach shows incorporation of the "orphan" subunit beta3
      into a functional nicotinic receptor.
AB  - We have investigated whether the neuronal nicotinic subunit beta3 can participate
      in the assembly of functional recombinant receptors. Although beta3 is expressed
      in several areas of the central nervous system, it does not form functional
      receptors when expressed heterologously together with an alpha or another beta
      nicotinic subunit. We inserted into the human beta3 subunit a reporter mutation
      (V273T), which, if incorporated into a functional receptor, would be expected to
      increase its agonist sensitivity and maximum response to partial agonists.
      Expressing the mutant beta3(V273T) in Xenopus oocytes together with both the
      alpha3 and the beta4 subunits resulted in the predicted changes in the properties
      of the resulting nicotinic receptor when compared with those of alpha3 beta4
      receptors. This indicated that some of the receptors incorporated the mutant
      beta3 subunit, as part of a "triplet" alpha3 beta4 beta3 receptor. The proportion
      of triplet receptors was dependent on the ratios of the alpha3:beta4:beta3 cRNA
      injected. We conclude that, like the related alpha5 subunit, the beta3 subunit
      can form functional receptors only if expressed together with both alpha and beta
      subunits.

PMID- 9624110
TI  - Xanthophyll cycle enzymes are members of the lipocalin family, the first
      identified from plants.
AB  - Violaxanthin de-epoxidase and zeaxanthin epoxidase catalyze the addition and
      removal of epoxide groups in carotenoids of the xanthophyll cycle in plants. The
      xanthophyll cycle is implicated in protecting the photosynthetic apparatus from
      excessive light. Two new sequences for violaxanthin de-epoxidase from tobacco and
      Arabidopsis are described. Although the mature proteins are well conserved, the
      transit peptides of these proteins are divergent, in contrast to transit peptides
      from other proteins targeted to the thylakoid lumen. Sequence analyses of both
      violaxanthin de-epoxidase and zeaxanthin epoxidase establish the xanthophyll
      cycle enzymes as members of the lipocalin family of proteins. The lipocalin
      family is a diverse group of proteins that bind small hydrophobic (lipophilic)
      molecules and share a conserved tertiary structure of eight beta-strands forming
      a barrel configuration. This is the first reported identification of lipocalin
      proteins in plants.

PMID- 9624111
TI  - Enhanced phosphorylation of Src family kinase substrates containing SH2 domain
      binding sites.
AB  - Src family protein-tyrosine kinases possess several modular domains important for
      regulation of catalytic activity and interaction with potential substrates. Here,
      we explore interactions between the SH2 domain of Hck, a Src family kinase, and
      substrates containing SH2 domain-binding sites. We have synthesized a series of
      peptide substrates containing a high affinity SH2 domain binding site,
      (phospho)Tyr-Glu-Glu-Ile. We show that the presence of this sequence in a peptide
      results in a dramatic increase in the phosphorylation rate of a second tyrosine
      located at the N terminus. Enhanced phosphorylation is not a consequence of
      stimulation of enzymatic activity by C-terminal tail displacement but is imparted
      instead by a 10-fold reduction in the Km of the phosphotyrosine-containing
      peptide when compared with a control. The isolated catalytic domain of the non
      receptor tyrosine kinase Abl does not show a preference for the pYEEI motif
      containing peptide; however, the preference is restored when the SH2 domain of
      Src is introduced into Abl. Furthermore, enhanced phosphorylation is dependent on
      the distance between SH2 domain-binding site and phosphorylatable tyrosine, with
      the minimum distance requirement being seven amino acids. Reversing the
      orientation of the pYEEI motif with respect to the substrate sequence decreases
      phosphorylation by down-regulated Hck, but both orientations are utilized equally
      well by activated Hck. We discuss the possible implications of these results for
      processive phosphorylation of substrates in vivo by Src family kinases.

PMID- 9624112
TI  - Thermodynamics of inositol hexakisphosphate interaction with human oxyhemoglobin.
AB  - The interaction of inositol hexakisphosphate (IHP) with oxygenated human adult
      hemoglobin (Hb) was investigated at 25 degreesC. The affinity of IHP for
      oxygenated Hb is strongly pH-dependent, and potentiometric measurements of proton
      uptake and release upon IHP addition have shown that over the range between pH
      8.0 and pH 6.0 in oxygenated Hb there are three groups of residues that change
      their pKa values after IHP addition, likely because of their interaction with
      negative charges of the heterotropic effector. On the basis of previous
      calculations on the electrostatic properties of human Hb (Matthew, J. B.,
      Hanania, G. I. H., and Gurd, F. R. N. (1979) Biochemistry 18, 1919-1928; Lee, A.
      W.-m., Karplus, M., Poyart, C., and Bursaux, E. (1988) Biochemistry 27, 1285
      1301), two of these groups might be Val1beta and His143beta, which are located in
      the beta1beta2 dyad axis, where they have been also proposed to interact with 2,3
      diphosphoglycerate, whereas the third group does not appear easily identifiable.
      Calorimetric measurements of the heat associated with IHP binding at different pH
      values over the same range indicate that IHP binding is mostly enthalpy-driven at
      pH < 7 and mostly entropy-driven at pH > 7.

PMID- 9624113
TI  - The key step in chlorophyll breakdown in higher plants. Cleavage of pheophorbide
      a macrocycle by a monooxygenase.
AB  - Chlorophyll breakdown in green plants is a long-standing biological enigma.
      Recent work has shown that pheophorbide a (Pheide a) derived from chlorophyll
      (Chl) is converted oxygenolytically into a primary fluorescent catabolite (pFCC
      1) via a red Chl catabolite (RCC) intermediate. RCC, the product of the ring
      cleavage reaction catalyzed by Pheide a oxygenase, which is suggested to be the
      key enzyme in Chl breakdown in green plants, is converted into pFCC-1 by a
      reductase. In the present study, an in vitro assay comprising 18O2 Pheide a
      oxygenase and RCC reductase yielded labeled pFCC-1. Fast atom bombardment-mass
      spectrometric analysis of the purified pFCC-1 product revealed that only one of
      the two oxygen atoms newly introduced into Pheide a in the course of the cleavage
      reaction is derived from molecular oxygen. Analysis of the fragment ions located
      the oxygen atom derived from molecular oxygen on the formyl group of pyrrole B.
      This finding demonstrates that the cleavage of Pheide a in vascular plants is
      catalyzed by a monooxygenase. Chlorophyll breakdown is therefore indicated to be
      mechanistically related in higher plants and in the green alga Chlorella
      protothecoides.

PMID- 9624114
TI  - Negative regulation of T cell antigen receptor signal transduction by
      hematopoietic tyrosine phosphatase (HePTP).
AB  - The hematopoietic tyrosine phosphatase (HePTP) is predominantly expressed in
      thymocytes and T lymphocytes and at lower levels in other hematopoietic cells.
      Expression of the gene is enhanced by the T cell growth factor interleukin-2,
      suggesting a role for HePTP in T cell proliferation or differentiation. We report
      that HePTP blocks T cell antigen receptor (TCR)-induced transcriptional
      activation of a reporter gene driven by a nuclear factor of activated T
      cells(NFAT)/AP-1 element taken from the interleukin-2 gene promoter. This effect
      was specific to HePTP and was abolished by a mutation (C270S) that impaired its
      phosphatase activity. Co-expression of HePTP also reduced TCR-induced activation
      of the mitogen-activated protein kinase Erk2 and the TCR-induced appearance of
      phosphorylated Erk. In contrast, HePTP did not affect the activation of the N
      terminal c-Jun kinase, Jnk. Together these findings suggest that HePTP plays an
      active negative role in TCR signaling by dephosphorylating one or several
      signaling molecules between the receptor and the mitogen-activated protein kinase
      pathway.

PMID- 9624115
TI  - Survival by Mac-1-mediated adherence and anoikis in phorbol ester-treated HL-60
      cells.
AB  - During the exposure of human myelocytic leukemia HL-60 cells to phorbol diester,
      nonadherent cells die by apoptosis, but adherent cells survive and growth-arrest
      at G1 phase of the cell cycle. Here we have shown that the adherent cells rapidly
      died by apoptosis after forced detachment (anoikis), indicating that phorbol
      diester induced apoptosis by default. Dimethylsphingosine induced apoptosis in
      the adherent cells, and sphingosine-1-phosphate rescued the detached cells from
      apoptosis. Sphingosine kinase activity in adherent cells was higher than that in
      nonadherent cells and was decreased by forced detachment. It is likely that the
      phorbol diester-induced apoptosis and the adhesion-mediated survival are
      modulated by sphingosine and sphingosine-1-phosphate, respectively. The adherent
      cells were reverted and reproliferated when allowed to spontaneously detach from
      plastic surfaces by removal of phorbol diester. This result suggests that after
      removal of phorbol diester, the commitment signal of apoptosis by default is lost
      faster than the survival signal by adherence.

PMID- 9624116
TI  - Catabolite inactivation of wild-type and mutant maltose transport proteins in
      Saccharomyces cerevisiae.
AB  - The maltose transporter of Saccharomyces cerevisiae is subject to rapid,
      irreversible inactivation in the presence of glucose. Loss of transport function
      was paralleled by a decrease in amount of transporter protein and most likely
      involves endocytosis and degradation of the protein in the vacuole. This
      (catabolite) inactivation of Mal61p was triggered not only by glucose but also by
      2-deoxy-D-glucose, which cannot be metabolized beyond 2-deoxy-D-glucose
      phosphate. The signal that targets membrane proteins specifically for catabolite
      inactivation is unknown. To investigate whether or not specific modification of
      Mal61p triggers the inactivation, putative protein kinase A and C phosphorylation
      sites were removed, and the transport activities and levels of the mutant
      proteins upon addition of glucose were followed in time. Three Mal61p mutants,
      i.e. S295A, T363A, and S487A, exhibited significantly reduced rates of
      inactivation in the presence of glucose. Likewise, in wild-type Mal61p the rate
      of inactivation and degradation of the protein paralleled each other in the case
      of T363A. On the contrary, for the S295A and S487A mutants the rates of protein
      degradation were slowed down more profoundly than was the loss of transport
      activity. These observations indicate that (i) some form of modification (e.g.
      phosphorylation) of the protein precedes breakdown, (ii) the modification
      inactivates Mal61p, and (iii) the inactivation of Mal61p is not necessarily
      followed by proteolytic degradation.

PMID- 9624117
TI  - A novel response to dioxin. Induction of ecto-ATPase gene expression.
AB  - We used differential display to discover a new gene that the environmental
      contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) regulates in mouse
      hepatoma cells. Its predicted amino acid sequence suggests that the gene encodes
      an ecto-ATPase that contains multiple glycosylation sites, conserved cysteine
      residues, and apyrase conserved regions. cDNA expression experiments in mouse
      hepatoma cells confirm that the new gene encodes an ecto-ATPase. Wild-type mouse
      hepatoma cells contain both constitutive and TCDD-inducible ecto-ATPase activity.
      Induction of ecto-ATPase gene expression by TCDD is direct and occurs at the
      transcriptional level. Studies in mutant hepatoma cells indicate that induction
      requires both the aromatic hydrocarbon receptor (AhR) and the AhR nuclear
      translocator (Arnt). Furthermore, induction requires AhR's transactivation
      domain, but not that of Arnt. Our findings reveal new aspects of dioxin's
      biological effects and TCDD-dependent gene regulation.

PMID- 9624118
TI  - Reversible inactivation of protein-tyrosine phosphatase 1B in A431 cells
      stimulated with epidermal growth factor.
AB  - Stimulation of various cells with growth factors results in a transient increase
      in the intracellular concentration of H2O2 that is required for growth factor
      induced protein tyrosine phosphorylation. The effect of H2O2 produced in response
      to epidermal growth factor (EGF) on the activity of protein-tyrosine phosphatase
      1B (PTP1B) was investigated in A431 human epidermoid carcinoma cells. H2O2
      inactivated recombinant PTP1B in vitro by oxidizing its catalytic site cysteine,
      most likely to sulfenic acid. The oxidized enzyme was reactivated more
      effectively by thioredoxin than by glutaredoxin or glutathione at their
      physiological concentrations. Oxidation by H2O2 prevented modification of the
      catalytic cysteine of PTP1B by iodoacetic acid, suggesting that it should be
      possible to monitor the oxidation state of PTP1B in cells by measuring the
      incorporation of radioactivity into the enzyme after lysis of the cells in the
      presence of radiolabeled iodoacetic acid. The amount of such radioactivity
      associated with PTP1B immunoprecipitated from A431 cells that had been stimulated
      with EGF for 10 min was 27% less than that associated with PTP1B from
      unstimulated cells. The amount of iodoacetic acid-derived radioactivity
      associated with PTP1B reached a minimum 10 min after stimulation of cells with
      EGF and returned to base line values by 40 min, suggesting that the oxidation of
      PTP1B is reversible in cells. These results indicate that the activation of a
      receptor tyrosine kinase by binding of the corresponding growth factor may not be
      sufficient to increase the steady state level of protein tyrosine phosphorylation
      in cells and that concurrent inhibition of protein-tyrosine phosphatases by H2O2
      might also be required.

PMID- 9624119
TI  - Regulation of the action of steroid/thyroid hormone receptors by medium-chain
      fatty acids.
AB  - Triiodothyronine (T3) causes a 30-fold increase in transcription of the malic
      enzyme gene in chick embryo hepatocytes; medium-chain fatty acids (MCFAs) inhibit
      this increase. T3 action is mediated by T3 receptors (TRs) that bind to T3
      response elements (T3REs) in this gene's 5'-flanking DNA. In transiently
      transfected hepatocytes, fragments of 5'-flanking DNA of the malic enzyme gene or
      artificial T3REs that conferred T3 stimulation also conferred MCFA inhibition to
      linked reporter genes. Thus, MCFA inhibition may be mediated through cis-acting
      T3REs and trans-acting TRs, distinguishing MCFA action from that of other fatty
      acids which act through unique sequence elements. Using binding assays and
      overexpression of TR, we showed that MCFAs inhibited the transactivating but not
      the silencing function of TR and did not alter binding of T3 to TR or of TR to
      T3RE. The C-terminal ligand-binding domain of TR was sufficient to confer
      stimulation by T3, but not inhibition by MCFA. Inhibition of transactivation by
      MCFA was specific: ligand-stimulated transcription from T3 or estrogen response
      elements was inhibited, but that from glucocorticoid or cyclic AMP response
      elements was not. We propose that MCFAs or metabolites thereof influence the
      activity of a factor(s) that interacts with the T3 and estrogen receptors to
      inhibit ligand-stimulated transcription.

PMID- 9624120
TI  - Role of ferritin in the control of the labile iron pool in murine erythroleukemia
      cells.
AB  - In vitro studies have shown that ferritin iron incorporation is mediated by a
      ferroxidase activity associated with ferritin H subunits (H-Ft) and a nucleation
      center associated with ferritin L subunits (L-Ft). To assess the role played by
      the ferritin subunits in regulating intracellular iron distribution, we
      transfected mouse erythroleukemia cells with the H-Ft subunit gene mutated in the
      iron-responsive element. Stable transfectants displayed high H-Ft levels and
      reduced endogenous L-Ft levels, resulting in a marked change in the H:L subunit
      ratio from 1:1 in control cells to as high as 20:1 in some transfected clones.
      The effects of H-Ft overexpression on the labile iron pool were determined in
      intact cells by a novel method based on the fluorescent metallosensor calcein. H
      Ft overexpression resulted in a significant reduction in the iron pool, from 1.3
      microM in control cells to 0.56 microM in H-Ft transfectants, and in higher
      buffering capacity following iron loads. A fraction of the H-Ft-associated iron
      was labile, available to cell-permeant, but not cell-impermeant, chelators. The
      results of this study provide the first in vivo direct demonstration of the
      capacity of H-Ft to sequester cell iron and to regulate the levels of the labile
      iron pool.

PMID- 9624121
TI  - Wild-type p53-mediated induction of rat mdr1b expression by the anticancer drug
      daunorubicin.
AB  - The expression of P-glycoproteins encoded by the mdr gene family is associated
      with the emergence of the multidrug resistance phenotype in animal cells. mdr
      expression can be induced by many extracellular stimulants including cytotoxic
      drugs and chemical carcinogens. However, little is known about the mechanisms
      involved. Here, we report that the expression of the rat mdr1b can be induced by
      anticancer drug daunorubicin. Further analysis identified a bona fide p53-binding
      site spanning from base pairs -199 to -180 (5'-GAACATGTAGAGACATGTCT-3') in the
      rat mdr1b promoter that is essential for basal and daunorubicin-inducible
      promoter activities. In addition, our results show that wild-type p53 can up
      regulate not only the promoter function but also endogenous expression of the rat
      mdr1b. To the best of our knowledge, this is the first report showing that a
      specific p53-binding site is involved in the transcriptional regulation of mdr
      gene by wild-type p53. Since p53 is a sensor for a wide variety of genotoxic
      stresses, our finding has broad implications for understanding the mechanisms
      involved in the inducible expression of mdr gene by anticancer drugs, chemical
      carcinogens, UV light, and other DNA-damaging agents.

PMID- 9624122
TI  - Two kinesin light chain genes in mice. Identification and characterization of the
      encoded proteins.
AB  - Native kinesin consists of two light chains and two heavy chains in a 1:1
      stoichiometric ratio. To date, only one gene for kinesin light chain has been
      characterized, while a second gene was identified in a genomic sequencing study
      but not analyzed biochemically. Here we describe new genes encoding kinesin light
      chains in mouse. One of these light chains is neuronally enriched, while another
      shows ubiquitous expression. The presence of multiple kinesin light chain genes
      in mice is especially interesting, since there are two kinesin heavy chain genes
      in humans (Niclas, J., Navone, F., Hom-Booher, N., and Vale, R. D. (1994) Neuron
      12, 1059-1072). To assess the selectivity of kinesin light chain interaction with
      the heavy chains, we performed immunoprecipitation experiments. The data
      suggested that the light chains form homodimers with no specificity in their
      interaction with the two heavy chains. Immunofluorescence and biochemical
      subfractionation suggested differences in the subcellular localization of the two
      kinesin light chain gene products. Although both kinesin light chains are
      distributed throughout the central and peripheral nervous systems, there is
      enrichment of one in sciatic nerve axons, while the other shows elevated levels
      in olfactory bulb glomeruli. These results indicate that the mammalian nervous
      system contains multiple kinesin light chain gene products with potentially
      distinct functions.

PMID- 9624123
TI  - The two [4Fe-4S] clusters in Chromatium vinosum ferredoxin have largely different
      reduction potentials. Structural origin and functional consequences.
AB  - The 2[4Fe-4S] ferredoxin from Chromatium vinosum arises as one prominent member
      of a recently defined family of proteins found in very diverse bacteria. The
      potentiometric circular dichroism titrations of the protein and of several
      molecular variants generated by site-directed mutagenesis have established that
      the reduction potentials of the two clusters differ widely by almost 200 mV. This
      large difference has been confirmed by electrochemical methods, and each redox
      transition has been assigned to one of the clusters. The unusually low potential
      center is surprisingly the one that displays a conventional CX1X2CX3X4C (Xn,
      variable amino acid) binding motif and a structural environment similar to that
      of clusters having less negative potentials. A comparison with other ferredoxins
      has highlighted factors contributing to the reduction potential of [4Fe-4S]
      clusters in proteins. (i) The loop between the coordinating cysteines 40 and 49
      and the C terminus alpha-helix of C. vinosum ferredoxin cause a negative, but
      relatively moderate, shift of approximately 60 mV for the nearby cluster. (ii)
      Very negative potentials, below -600 mV, correlate with the presence of a bulky
      side chain in position X4 of the coordinating triad of cysteines. These findings
      set the framework in which previous observations on ferredoxins can be better
      understood. They also shed light onto the possible occurrence and properties of
      very low potential [4Fe-4S] clusters in less well characterized proteins.

PMID- 9624124
TI  - Characterization of a novel manganese peroxidase-lignin peroxidase hybrid isozyme
      produced by Bjerkandera species strain BOS55 in the absence of manganese.
AB  - A novel manganese-dependent peroxidase (MnP) isozyme produced in manganese-free
      cultures of Bjerkandera sp. strain BOS55 was purified and characterized. The
      production of the enzyme was greatly stimulated by the exogenous addition of
      various physiological organic acids such as glycolate, glyoxylate, and oxalate.
      The physical properties of the enzyme are similar to those of MnP isozymes from
      different white rot fungi (Mr = 43,000, pI 3.88, and epsilon407 nm = 123 mM-1 cm
      1). The Bjerkandera MnP was efficient in the oxidation of Mn(II), as indicated by
      the kinetic constants (low Km of 51 microM and turnover number of 59 s-1).
      Furthermore, the isozyme was able to oxidize various substrates in the absence of
      manganese, such as 2,6-dimethoxyphenol, guaiacol, ABTS, 3-hydroxyanthranilic
      acid, and o- and p-anisidine. An interesting characteristic of the isozyme was
      its ability to oxidize nonphenolic substrates, veratryl alcohol and 1,4
      dimethoxybenzene, without manganese addition. The affinity for veratryl alcohol
      (Km = 116 microM) and its turnover number (2.8 s-1) are comparable to those of
      lignin peroxidase (LiP) isozymes from other white rot fungi. Manganese at
      concentrations greater than 0.1 mM severely inhibited the oxidation of veratryl
      alcohol. The results suggest that this single isozyme is a hybrid between MnP and
      LiP found in other white rot fungi. The N-terminal amino acid sequence showed a
      very high homology to those of both MnP and LiP isozymes from Trametes
      versicolor.

PMID- 9624125
TI  - Mutations causing neurodegeneration in Caenorhabditis elegans drastically alter
      the pH sensitivity and inactivation of the mammalian H+-gated Na+ channel MDEG1.
AB  - The mammalian degenerin MDEG1 belongs to the nematode degenerin/epithelial Na+
      channel superfamily. It is constitutively activated by the same mutations that
      cause gain-of-function of the Caenorhabditis elegans degenerins and
      neurodegeneration. ASIC and DRASIC, which were recently cloned, are structural
      homologues of MDEG1 and behave as H+-gated cation channels. MDEG1 is also a H+
      activated Na+ channel, but it differs from ASIC in its lower pH sensitivity and
      slower kinetics. In addition to the generation of a constitutive current,
      mutations in MDEG1 also alter the properties of the H+-gated current. Replacement
      of Gly-430 in MDEG1 by bulkier amino acids, such as Val, Phe, or Thr, drastically
      increases the H+ sensitivity of the channel (half-maximal pH (pHm) approximately
      4.4 for MDEG1, pHm approximately 6.7 for the different mutants). Furthermore,
      these replacements completely suppress the inactivation observed with the wild
      type channel and increase the sensitivity of the H+-gated channel to blockade by
      amiloride by a factor of 10 without modification of its conductance and ionic
      selectivity. These results as well as those obtained with other mutants clearly
      indicate that the region surrounding Gly-430, situated just before the second
      transmembrane segment, is essential for pH sensitivity and gating.

PMID- 9624126
TI  - Identification of a novel type of silk protein and regulation of its expression.
AB  - The silk of lepidopteran insects has been studied extensively as proteins of two
      categories: the fibroins, which are produced in the posterior section of silk
      glands, and the sericins, which are secreted in the middle section. We now
      describe a third category that is named seroins to accentuate the fact that both
      the sericin- and the fibroin-producing cells participate in seroin secretion.
      Using a probe derived from the N-terminal sequences of a 23-kDa components of
      Galleria mellonella silk, we isolated silk gland-specific cDNA encoding 167 amino
      acids, of which 17 constitute the signal peptide. The following 14 residues match
      the N-terminal sequences of the 23- and 22.5-kDa silk proteines. The reaction of
      these proteins with concanavalin A and the presence of two glycosylation sites in
      the seroin peptide sequence indicate that seroin is secreted in two forms that
      both contain a mannose-rich sugar moiety. Seroin is distinguished from other silk
      proteins by high proline content (34 residues or 20.26% by weight), lack of
      cysteines, and the presence of two kinds of short amino acid repeats. The seroin
      gene is expressed in both the posterior and middle silk gland sections. The
      expression fluctuates during development in correlation with the feeding regime
      and the changes in hormone titers: seroin mRNA is high in the silk glands of
      feeding larvae, declines at ecdysis, reaches a maximum during cocoon spinning,
      and thereafter rapidly drops to an undetectable level. In vivo and in vitro
      experiments showed that the drop is caused by ecdysteroid hormones and is
      prevented by juvenile hormones. N-terminal sequencing of several silk proteins of
      Bombyx mori revealed that the 8- and 13-kDa proteins share 5 or 6 out of 10
      identified amino acids with the N terminus of Galleria seroin and obviously
      represent seroin homologues. The result suggests that seroin-type proteins are a
      general component of lepidopteran silk.

PMID- 9624127
TI  - Molecular mechanism of human CD38 gene expression by retinoic acid.
      Identification of retinoic acid response element in the first intron.
AB  - CD38 is a nonlineage-restricted type II transmembrane glycoprotein possessing
      ecto-NAD+ glycohydrolase activity. Because of its unique expression pattern in
      lymphocyte differentiation, it appears to function as an immunoregulatory
      molecule. We previously reported that CD38 was specifically induced by all-trans
      retinoic acid (RA) in human promyelocytic leukemia HL-60 cells. Here we studied
      the molecular mechanism of the RA-dependent induction of human CD38. The
      expression of CD38 mRNA by RA appeared to be caused by the transcriptional
      stimulation of the gene, since it was blocked by an RNA synthesis inhibitor, but
      not by a protein synthesis inhibitor. In search of the RA response element (RARE)
      possibly present in human CD38 gene promoter, we isolated and sequenced the
      genomic DNA covering the 5'-flanking region, exon 1, and partial intron 1.
      Transient transfection experiments revealed that the responsiveness to RA was
      conferred through an RARE consisting of two direct repeat TGACCT-like hexamer
      motifs with a 5-nucleotide spacer, which was located in the first intron rather
      than the 5'-flanking region of the CD38 gene. This RARE interacted with
      heterodimer composed of RA receptor and retinoid X receptor in vitro. Thus, the
      RA-induced expression of the human CD38 gene was demonstrated to be mediated
      through the RARE located in the first intron.

PMID- 9624128
TI  - Mapping of functional domains in p47(phox) involved in the activation of NADPH
      oxidase by "peptide walking".
AB  - The superoxide generating NADPH oxidase of phagocytes consists, in resting cells,
      of a membrane-associated electron transporting flavocytochrome (cytochrome b559)
      and four cytosolic proteins as follows: p47(phox), p67(phox), p40(phox), and the
      small GTPase, Rac(1 or 2). Activation of the oxidase is consequent to the
      assembly of a membrane-localized multimolecular complex consisting of cytochrome
      b559 and the cytosolic components. We used "peptide walking" (Joseph, G., and
      Pick, E. (1995) J. Biol. Chem. 270, 29079-29082) for mapping domains in the amino
      acid sequence of p47(phox) participating in the molecular events leading to the
      activation of NADPH oxidase. Ninety-five overlapping pentadecapeptides, with a
      four-residue offset between neighboring peptides, spanning the complete p47(phox)
      sequence, were tested for the ability to inhibit NADPH oxidase activation in a
      cell-free system. This consisted of solubilized macrophage membranes, recombinant
      p47(phox), p67(phox), and Rac1, and lithium dodecyl sulfate, as the activator.
      Eight functional domains were identified and labeled a-h. These were (N- and C
      terminal residue numbers are given for each domain) as follows: a (21-35); b (105
      119); c (149-159); d (193-207); e (253-267); f (305-319); g (325-339), and h (373
      387). Four of these domains (c, d, e, and g) correspond to or form parts of
      regions shown before to participate in NADPH oxidase assembly. Thus, domain c
      corresponds to a region on the N-terminal boundary of the first src homology 3
      (SH3) domain, whereas domains d and e represent more precisely defined sites
      within the full-length first and second SH3 domains, respectively. Domain g
      overlaps an extensively investigated arginine-rich region. Domains a and b, in
      the N-terminal half of p47(phox), and domains f and h, in the C-terminal half,
      represent newly identified entities, for which there is no earlier experimental
      evidence of involvement in NADPH oxidase activation. "Peptide walking" was also
      applied to the identification of domains in p47(phox) mediating binding to
      p67(phox). This was done by quantifying, by enzyme-linked immunosorbent assay,
      the binding of p67(phox), in solution, to a series of 95 overlapping biotinylated
      p47(phox) peptides, attached to streptavidin-coated 96-well plates. A single
      proline-rich domain (residues 357-371) was found to bind p67(phox) in the absence
      and presence of lithium dodecyl sulfate.

PMID- 9624129
TI  - T cell activation induced by novel gain-of-function mutants of Syk and ZAP-70.
AB  - The Syk family tyrosine kinases play a crucial role in antigen receptor-mediated
      signal transduction, but their regulation and cellular targets remain
      incompletely defined. Following receptor engagement, phosphorylation of tyrosine
      residues within ZAP-70 and Syk is thought to control both kinase activity and
      recruitment of modulatory factors. We report here the characterization of novel
      mutants of ZAP-70 and Syk, in which conserved C-terminal tyrosine residues have
      been replaced by phenylalanines (ZAP YF-C, Syk YF-C). Both mutant kinases display
      a prominent gain-of-function phenotype in Jurkat T cells, as demonstrated by
      lymphokine promoter activation, tyrosine phosphorylation of potential targets in
      vivo, and elevated intracellular calcium mobilization. While the presence of p56
      Lck was required for ZAP YF-C-induced signaling, Syk YF-C showed enhanced
      functional activity in Lck-deficient JCaM1 Jurkat cells. Our results implicate
      the C terminus of Syk family kinases as an important regulatory region modulating
      T cell activation.

PMID- 9624130
TI  - Activation of G1 progression, JNK mitogen-activated protein kinase, and actin
      filament assembly by the exchange factor FGD1.
AB  - Cdc42 has been shown to control bifurcating pathways leading to filopodia
      formation/G1 cell cycle progression and to JNK mitogen-activated protein kinase
      activation. To dissect these pathways further, the cellular effects induced by a
      Cdc42 guanine nucleotide exchange factor, FGD1, have been examined. All exchange
      factors acting on the Rho GTPase family have juxtaposed Dbl homology (DH) and
      pleckstrin homology (PH) domains. We report here that FGD1 triggers G1 cell cycle
      progression and filopodia formation in Swiss 3T3 fibroblasts as well as JNK
      mitogen-activated protein kinase activation in COS cell transfection assays. FGD1
      induced filopodia formation is Cdc42-dependent, and both the DH and PH domains
      are essential. Although expression of the FGD1 DH domain alone does not activate
      Cdc42 and induce filopodia, it does trigger both the JNK cascade in COS cells and
      G1 progression in quiescent Swiss 3T3 cells. We conclude that FGD1 can trigger G1
      progression independently of actin polymerization or integrin adhesion complex
      assembly. Furthermore, since FGD1 activates JNK and G1 progression in a Cdc42
      independent manner, it must have additional, as yet unidentified, targets.

PMID- 9624131
TI  - pi-Stacking interactions. Alive and well in proteins.
AB  - A representative set of high resolution x-ray crystal structures of nonhomologous
      proteins have been examined to determine the preferred positions and orientations
      of noncovalent interactions between the aromatic side chains of the amino acids
      phenylalanine, tyrosine, histidine, and tryptophan. To study the primary
      interactions between aromatic amino acids, care has been taken to examine only
      isolated pairs (dimers) of amino acids because trimers and higher order clusters
      of aromatic amino acids behave differently than their dimer counterparts. We find
      that pairs (dimers) of aromatic side chain amino acids preferentially align their
      respective aromatic rings in an off-centered parallel orientation. Further, we
      find that this parallel-displaced structure is 0.5-0.75 kcal/mol more stable than
      a T-shaped structure for phenylalanine interactions and 1 kcal/mol more stable
      than a T-shaped structure for the full set of aromatic side chain amino acids.
      This experimentally determined structure and energy difference is consistent with
      ab initio and molecular mechanics calculations of benzene dimer, however, the
      results are not in agreement with previously published analyses of aromatic amino
      acids in proteins. The preferred orientation is referred to as parallel displaced
      pi-stacking.

PMID- 9624132
TI  - Expression, purification, and reconstitution of receptor for pituitary adenylate
      cyclase-activating polypeptide. large-scale purification of a functionally active
      G protein-coupled receptor produced in Sf9 insect cells.
AB  - Human pituitary adenylate cyclase-activating polypeptide (PACAP) receptor was
      expressed in Sf9 insect cells and Chinese hamster ovary (CHO) cells. The
      recombinant receptor in Sf9 cell membranes had low affinity for 125I-PACAP27 (Kd
      = 155.3 pM) and was insensitive to guanosine 5'-O-3-thiotriphosphate (GTPgammaS),
      whereas the receptor in CHO membranes had a high affinity (Kd = 44.4 pM) and was
      GTPgammaS sensitive. The receptor in Sf9 membranes was converted to a high
      affinity state (Kd = 20-40 pM) following solubilization with digitonin. A large
      quantity (2 mg from 8 liters of insect cells) of the purified PACAP receptors
      (Bmax = 23.9 nmol/mg of protein) were obtained in a digitonin-induced high
      affinity state (Kd = 17.3 pM) using biotinylated ligand affinity chromatography.
      The apparent molecular weight of the purified receptor (Mr = 48,000) was smaller
      than that of the receptor from CHO cells (Mr = 58,000) due to differences in
      asparagine-linked sugar chains. The purified receptor reverted to a low affinity
      state (Kd = 182.6 pM) upon reconstitution into lipid vesicles, however, the
      receptor reconstituted with Gs protein had a high affinity (Kd = 40.2 pM) and was
      GTPgammaS sensitive. [35S]GTPgammaS binding to the reconstituted Gs protein was
      enhanced by PACAP27 and PACAP38 (EC50 = 42.5 and 9.4 pM, respectively) but not by
      antagonist PACAP(6-38), indicating that the purified receptor was functionally
      active.

PMID- 9624133
TI  - Identification of 1,1'-bi(4-anilino)naphthalene-5,5'-disulfonic acid binding
      sequences in alpha-crystallin.
AB  - The hydrophobic binding sites in alpha-crystallin were evaluated using
      fluorescent probes 1,1'-bi(4-anilino)naphthalenesulfonic acid (bis-ANS), 8
      anilino-1-naphthalene sulfonate (ANS), and 1-azidonaphthalene 5-sulfonate (1,5
      AZNS). The photolysis of bis-ANS-alpha-crystallin complex resulted in
      incorporation of the probe to both alphaA- and alphaB-subunits. Prior binding of
      denatured alcohol dehydrogenase to alpha-crystallin significantly decreased the
      photoincorporation of bis-ANS to alpha-crystallin. Localization of bis-ANS
      incorporated into alphaA-crystallin resulted in the identification of residues
      QSLFR and HFSPEDLTVK as the fluorophore binding regions. In alphaB-crystallin,
      sequences DRFSVNLNVK and VLGDVIEVHGK were found to be the bis-ANS binding
      regions. Of the bis-ANS binding sequences, HFSPEDLTVK of alphaA-crystallin and
      DRFSVNLNVK and VLGDVIEVHGK of alphaB-crystallin were earlier identified as part
      of the sequences involved in their interaction with target proteins during the
      molecular chaperone-like action. The hydrophobic probe, 1,5-AZNS, also interacted
      with both subunits of alpha-crystallin. Localization of 1,5-AZNS binding site in
      alphaB-crystallin lead to the identification of HFSPEEK sequence as the
      interacting site in this subunit of alpha-crystallin. Glycated alpha-crystallin
      displayed decreased ANS fluorescence and loss of chaperone-like function,
      suggesting the involvement of glycation site as well as ANS binding site in
      chaperone-like activity display.

PMID- 9624135
TI  - Defining the interleukin-8-binding domain of heparan sulfate.
AB  - Interleukin-8, a member of the CXC chemokine family, has been shown to bind to
      glycosaminoglycans. It has been suggested that heparan sulfate on cell surfaces
      could provide specific ligand sites on endothelial cells to retain the highly
      diffusible inflammatory chemokine for presentation to leukocytes. By using
      selectively modified heparin and heparan sulfate fragments in a nitrocellulose
      filter trapping system, we have analyzed sequence requirements for interleukin-8
      binding to heparin/heparan sulfate. We demonstrate that the affinity of a
      monomeric interleukin-8 molecule for heparin/heparan sulfate is too weak to allow
      binding at physiological ionic strength, whereas the dimeric form of the protein
      mediates binding to two sulfated domains of heparan sulfate. These domains, each
      an N-sulfated block of approximately 6 monosaccharide units, are contained within
      an approximately 22-24-mer sequence and are separated by a region of </=14
      monosaccharide residues that may be fully N-acetylated. Binding to interleukin-8
      correlates with the occurrence of the di-O-sulfated disaccharide unit -IdceA(2
      OSO3)-GlcNSO3(6-OSO3)-. We suggest that the heparan sulfate sequence binds in
      horseshoe fashion over two antiparallel-oriented helical regions on the dimeric
      protein.

PMID- 9624134
TI  - RNA-dependent RNA polymerase activity of the soluble recombinant hepatitis C
      virus NS5B protein truncated at the C-terminal region.
AB  - The hepatitis C virus (HCV) NS5B protein encodes an RNA-dependent RNA polymerase
      (RdRP), which is the central catalytic enzyme of HCV replicase. We established a
      new method to purify soluble HCV NS5B in the glutathione S-transferase-fused form
      NS5Bt from Escherichia coli which lacks the C-terminal 21 amino acid residues
      encompassing a putative anchoring domain (anino acids 2990-3010). The recombinant
      soluble protein exhibited RdRP activity in vitro which was dependent upon the
      template and primer, but it did not exhibit the terminal transferase activity
      that has been reported to be associated with the recombinant NS5B protein from
      insect cells. The RdRP activity of purified glutathione S-transferase-NS5Bt and
      thrombin-cleavaged non-fused NS5Bt shares most of the properties. Substitution
      mutations of NS5Bt at the GDD motif, which is highly conserved among viral RdRPs,
      and at the clustered basic residues (amino acids 2919-2924 and 2693-2699)
      abolished the RdRP activity. The C-terminal region of NS5B, which is dispensable
      for the RdRP activity, dramatically affected the subcellular localization of NS5B
      retaining it in perinuclear sites in transiently overexpressed mammalian cells.
      These results may provide some clues to dissecting the molecular mechanism of the
      HCV replication and also act as a basis for developing new anti-viral drugs.

PMID- 9624136
TI  - Ceramide activates NFkappaB by inducing the processing of p105.
AB  - The role of ceramide as a second messenger in tumor necrosis factor (TNF)
      mediated signal transduction has been much debated. It is supported by recent
      reports describing an expanding number of potential targets for this lipid, but
      is opposed by those describing how ceramide is not necessary for many TNF
      mediated cellular events. In this paper, we directly compare the effects of the
      cell-permeable ceramide analogue, N-acetylsphingosine (C2-ceramide), with TNF, on
      NFkappaB function, a transcription factor whose activation is central to many TNF
      mediated effects. We describe how C2-ceramide failed to drive kappaB-linked
      chloramphenicol acetyltransferase gene expression in either HL60 promyelocytic or
      Jurkat T lymphoma cells. Furthermore, it had no effect on TNF-mediated
      transcription of this reporter gene. However, electrophoretic mobility shift
      analysis following cell stimulation with this ceramide analogue revealed a dose
      responsive activation of NFkappaB, which was not apparent following cell
      treatment with the inactive dihydro form. Activated complexes from treated cells
      were shown to contain predominantly the p50 subunit, in contrast to complexes
      from TNF-treated cells, where both p50 and p65/RelA subunits were present. The
      specific activation of p50 homodimeric complexes by C2-ceramide, which are known
      to lack trans-activating activity, was strongly suggested from these data.
      Further investigations revealed that C2-ceramide had only a marginal effect on
      IkappaBalpha degradation but strongly promoted the processing of p105 to its p50
      product as revealed by immunoblot analysis. The increase in p50 arising from the
      processing of its p105 precursor was further established from p105/p50 ratios
      obtained by scanning densitometric analysis of bands from immunoblots. TNF, on
      the other hand, stimulated both IkappaBalpha degradation and p105 processing, in
      accordance with previous findings. Furthermore, the effect of TNF on NFkappaB
      activation was rapid, whereas C2-ceramide required an optimal treatment time of 1
      h. Interestingly, TNF was found to increase ceramide in cells but only after a 1
      h contact time. Our data therefore suggest that ceramide promotes the activation
      of NFkappaB complexes that lack transactivating activity by enhanced processing
      of p105.

PMID- 9624137
TI  - The selectivity of visual arrestin for light-activated phosphorhodopsin is
      controlled by multiple nonredundant mechanisms.
AB  - Arrestin plays an important role in quenching phototransduction via its ability
      to bind to the phosphorylated light-activated form of the visual receptor
      rhodopsin (P-Rh*). Remarkable selectivity of visual arrestin toward this
      functional form is determined by an elegant sequential multisite binding
      mechanism. Previous structure-function studies have suggested that the COOH
      terminal region of arrestin (residues 356-404) is not directly involved in
      rhodopsin interaction, but instead plays a regulatory role. This region supports
      basal arrestin conformation and ensures arrestin's transition into a high
      affinity rhodopsin-binding state upon an encounter with P-Rh*. Overall, our
      results corroborate this hypothesis and identify three functional subregions
      (residues 361-368, 369-378, and 379-404) and individual amino acids involved in
      the control of arrestin stability and binding selectivity. Two of the most potent
      mutants, arrestin(1-378) and arrestin(F375A,V376A, F377A) belong to a novel class
      of constitutively active arrestins with high affinity for P-Rh*, dark P-Rh, and
      Rh* (but not dark Rh), in contrast to earlier constructed mutants arrestin(R175E)
      and arrestin(Delta2-16) with high affinity for light-activated forms only. The
      implications of these findings for the mechanism of arrestin-rhodopsin
      interaction are discussed in light of the recently determined crystal structure
      of arrestin.

PMID- 9624138
TI  - Rapid activation and nuclear translocation of mitogen-activated protein kinases
      in response to physiological concentration of glucose in the MIN6 pancreatic beta
      cell line.
AB  - MIN6 is one of the few pancreatic beta cell lines that respond to physiological
      concentrations of glucose by secreting insulin, and little is known about the
      triggered molecular mechanisms. We report below that the response to glucose in
      the MIN6 cells includes an activation of the p42 and p44 mitogen-activated
      protein (MAP) kinases (ERK2 and ERK1). This activation also occurred with the
      antidiabetic sulfonylurea glibenclamide and kainate, a specific agonist of a
      subtype of the ionotropic glutamate receptors, which depolarize the cytoplasmic
      membrane. The requirement for a calcium entry through the L-type voltage-gated
      channels and other characteristics of the regulation of the MAP kinase activity,
      such as the effect of the elevation of the cAMP concentration by forskolin, were
      similar to those of the secretion of insulin. However, the activation of the MAP
      kinases is not required for the secretion of insulin, inasmuch as this effect of
      glucose was not abolished when the MAP kinases were prevented from activation by
      PD098059, an inhibitor of the MAP kinase kinase. However, as the MAP kinases were
      translocated into the nucleus, they might be implicated in the calcium-dependent
      transcriptional response of the cells to glucose and thus regulate the expression
      of the insulin gene.

PMID- 9624139
TI  - Regulated expression, processing, and secretion of dog mast cell dipeptidyl
      peptidase I.
AB  - Dipeptidyl peptidase I (DPPI) is a cysteine protease found predominantly in
      myelomonocytic cells, cytotoxic T-cells, and mast cells. Recent studies identify
      an intracellular role for mast cell-DPPI (MC-DPPI) by activating prochymase and
      protryptase to their mature forms. To better define MC-DPPI and to explore the
      possibility of extracellular roles, we purified MC-DPPI from mastocytoma cells.
      We found the dog C2 mastocytoma cell line to be the richest source yet described
      for DPPI, purifying up to 200 microg of enzyme per g of cells. Dog MC-DPPI has an
      Mr of approximately 175,000 and consists of four subunits, each composed of a
      propeptide, light chain, and heavy chain. The heavy chain is N-glycosylated and
      is heterogeneously processed to three different forms. NH2-terminal sequences of
      the heavy chain and propeptide are identical to those predicted from a cDNA clone
      we sequenced from a mastocytoma cDNA library. The dog cDNA-derived sequence is
      86% identical to that of human DPPI. Dog mastocytoma cells incubated with 12-O
      tetradecanoylphorbol-13-acetate increase expression of MC-DPPI mRNA. MC-DPPI
      maintains its activity for dipeptide substrates at a neutral to alkaline pH.
      Cells stimulated with ionophore or substance P secrete MC-DPPI in parallel with
      the granule-associated mediators tryptase and histamine. Thus, dog mastocytoma
      cells secrete DPPI that is active at the pH of extracellular fluids, suggesting
      that MC-DPPI may act outside the cell.

PMID- 9624140
TI  - Purified recombinant Fmrp exhibits selective RNA binding as an intrinsic property
      of the fragile X mental retardation protein.
AB  - Fragile X syndrome is caused by the transcriptional silencing of the FMR1 gene
      due to a trinucleotide repeat expansion. The encoded protein, Fmrp, has been
      found to be a nucleocytoplasmic RNA-binding protein containing both KH domains
      and RGG boxes that associates with polyribosomes as a ribonucleoprotein particle.
      RNA binding has previously been demonstrated with in vitro-translated Fmrp;
      however, it remained uncertain whether the selective RNA binding observed was an
      intrinsic property of Fmrp or required an associated protein(s). Here,
      baculovirus-expressed and affinity-purified FLAG-tagged murine Fmrp was shown to
      bind directly to both ribonucleotide homopolymers and human brain mRNA. FLAG-Fmrp
      exhibited selectivity for binding poly(G) > poly(U) >> poly(C) or poly(A).
      Moreover, purified FLAG-Fmrp bound to only a subset of brain mRNA, including the
      3' untranslated regions of myelin basic protein message and its own message.
      Recombinant isoform 4, lacking the RGG boxes but maintaining both KH domains, was
      also purified and was found to only weakly interact with RNA. FLAG-purified I304N
      Fmrp, harboring the mutation of severe fragile X syndrome, demonstrated RNA
      binding, in contrast to previous suggestions. These data demonstrate the
      intrinsic property of Fmrp to selectively bind RNA and show FLAG-Fmrp as a
      suitable reagent for structural characterization and identification of cognate
      RNA ligands.

PMID- 9624141
TI  - The uncoupling protein UCP1 does not increase the proton conductance of the inner
      mitochondrial membrane by functioning as a fatty acid anion transporter.
AB  - The activity of the brown fat uncoupling protein (UCP1) is regulated by purine
      nucleotides and fatty acids. Although the inhibition by nucleotides is well
      established, the activation by fatty acids is still controversial. It has been
      reported that the ADP/ATP carrier, and possibly other members of the
      mitochondrial carrier family, mediate fatty acid uncoupling of mitochondria from
      a variety of sources by facilitating the transbilayer movement of the fatty acid
      anion. Brown fat mitochondria are known to be more sensitive to fatty acid
      uncoupling, a property that has been assigned to the presence of UCP1. We have
      analyzed the transport properties of UCP1 and conclude that fatty acids are not
      essential for UCP1 function, although they increase its uncoupling activity. In
      order to establish the difference between the proposed carrier-mediated
      uncoupling and that exerted through UCP1, we have studied the facility with which
      fatty acids uncouple respiration in mitochondria from control yeast and strains
      expressing UCP1 or the mutant Cys-304 --> Gly. The concentration of free
      palmitate required for half-maximal activation of respiration in UCP1-expressing
      mitochondria is 80 or 40 nM for the mutant protein. These concentrations have
      virtually no effect on the respiration of mitochondria from control yeast and are
      nearly 3 orders of magnitude lower than those reported for carrier-mediated
      uncoupling. We propose that there exist two modes of fatty acid-mediated
      uncoupling; nanomolar concentrations activate proton transport through UCP1, but
      only if their concentrations rise to the micromolar range do they become
      substrates for nonspecific carrier-mediated uncoupling.

PMID- 9624142
TI  - Identification and characterization of the major phosphorylation sites of the B
      type natriuretic peptide receptor.
AB  - C-type natriuretic peptide (CNP) is a newly discovered factor that stimulates
      vasorelaxation and inhibits cell proliferation. Natriuretic peptide receptor-B
      (NPR-B) is the primary signaling molecule for CNP. Recently, the guanylyl cyclase
      activity of NPR-B was shown to correlate with its phosphorylation state, and it
      was suggested that receptor dephosphorylation is a mechanism of desensitization.
      We now report the identification and characterization of the major NPR-B
      phosphorylation sites. Mutagenesis and comigration studies using synthetic
      phosphopeptides were employed to identify five residues (Ser-513, Thr-516, Ser
      518, Ser-523, and Ser-526) within the kinase homology domain that are
      phosphorylated when NPR-B is expressed in human 293 cells. Mutation of any of
      these residues to alanine reduced the receptor's phosphorylation state and CNP
      dependent guanylyl cyclase activity. The reductions were not explained by
      decreases in receptor protein level as indicated by immunoblot analysis and
      determinations of cyclase activity in the absence of CNP or in the presence of
      detergent. Elimination of all of the phosphorylation sites resulted in a
      completely dephosphorylated receptor whose CNP-dependent cyclase activity was
      decreased by >90%. However, unlike NPR-A, the dephosphorylated receptor was not
      completely unresponsive to hormone. Finally, two additional residues (Gly-521 and
      Ser-522) were identified that when mutated to alanine reduced the overall
      phosphorylation state and hormone responsiveness of the receptor without
      abolishing the phosphorylation of a specific site. These data indicate that
      phosphorylation of the kinase homology domain is a critical event in the
      regulation of NPR-B.

PMID- 9624143
TI  - Caspase-3 is required for alpha-fodrin cleavage but dispensable for cleavage of
      other death substrates in apoptosis.
AB  - Although the commonly activated death protease caspase-3 appears not to be
      essential for apoptosis during development except in the brain, it was not shown
      whether substrates known to be cleaved by caspase-3 are still proteolyzed in its
      absence. We have addressed this question with MCF-7 breast carcinoma cells that
      we recently showed lack caspase-3 owing to the functional deletion of the CASP-3
      gene. Tumor necrosis factor- or staurosporine-induced apoptosis of caspase-3
      deficient MCF-7 cells resulted in cleavage of the death substrates PARP, Rb,
      PAK2, DNA-PKcs, gelsolin, and DFF-45, but not alpha-fodrin. In contrast, all
      these substrates including alpha-fodrin were cleaved in apoptotic HeLa cells
      expressing caspase-3. Introduction of CASP-3 cDNA, but not CASP-10 cDNA, into MCF
      7 cells restored alpha-fodrin cleavage. In addition, tumor necrosis factor- or
      staurosporine-induced apoptosis of MCF-7 cells stably expressing pro-caspase-3
      also resulted in alpha-fodrin cleavage. Although the specific caspase inhibitory
      peptides Z-VAD-fmk and Z-DEVD-fmk prevented apoptosis of MCF-7 cells, we were
      unable to detect activation of caspases 2 and 7, which are known to be inhibited
      by Z-DEVD-fmk. Together our results suggest that caspase-3 is essential for
      cleavage of alpha-fodrin, but dispensable for the cleavage of PARP, Rb, PAK2, DNA
      PKcs, gelsolin, and DFF-45 and imply that one or more caspases other than
      caspases 2, 3, and 7 is activated and plays a crucial role in the cleavage of
      these substrates in MCF-7 cells.

PMID- 9624144
TI  - The ATPase activity of Hsp104, effects of environmental conditions and mutations.
AB  - Hsp104 is crucial for stress tolerance in Saccharomyces cerevisiae, and both of
      its nucleotide-binding domains (NBD1 and NBD2) are required. Here, we
      characterize the ATPase activity and oligomerization properties of wild-type (WT)
      Hsp104 and of NBD mutants. In physiological ionic strength buffers (pH 7.5, 37
      degreesC) WT Hsp104 exhibits Michaelis-Menten kinetics between 0.5 and 25 mM ATP
      (Km approximately 5 mM, Vmax approximately 2 nmol min-1 microg-1). ATPase
      activity is strongly influenced by factors that vary with cell stress (e.g.
      temperature, pH, and ADP). Mutations in the P-loop of NBD1 (G217V or K218T)
      severely reduce ATP hydrolysis but have little effect on oligomerization.
      Analogous mutations in NBD2 (G619V or K620T) have smaller effects on ATPase
      activity but impair oligomerization. The opposite relationship was reported for
      another member of the HSP100 protein family, the Escherichia coli ClpA protein,
      in studies employing lower ionic strength buffers. In such buffers, the Km of WT
      Hsp104 for ATP hydrolysis decreased 10-fold and its stability under stress
      conditions increased, but the effects of the NBD mutations on ATPase activity and
      oligomerization remained opposite to those of ClpA. Either the functions of the
      two NBDs in ClpA and Hsp104 have been reversed or both contribute to ATP
      hydrolysis and oligomerization in a complex manner that can be idiosyncratically
      affected by such mutations.

PMID- 9624145
TI  - Identification and characterization of a novel family of cyclic nucleotide
      phosphodiesterases.
AB  - We report the cloning, expression, and characterization of a new family of cyclic
      nucleotide phosphodiesterase (PDE) that has unique kinetic and inhibitor
      specificities. A clone corresponding to the C terminus of this PDE was initially
      identified by a bioinformatic approach and used to isolate a cDNA that is likely
      full-length. This novel PDE, designated as MMPDE9A1, shows highest mRNA
      expression in kidney with lower levels in liver, lung, and brain. The mRNA size
      by Northern blot analysis is approximately 2.0 kilobases, and the cDNA encoding
      PDE9A1 is 1929 base pairs in length. The largest open reading frame predicts a
      protein of 534 amino acids with a molecular mass of 62,000 Da. When expressed in
      COS-7 cells, PDE9A1 activity was not inhibited well by either the nonselective
      inhibitor 3-isobutyl-1-methyl-xanthine or the new selective PDE5 inhibitor,
      sildenafil, but it is inhibited by the PDE1/5 inhibitor (+)-cis-5,6a, 7,8,9 hyl]
      phenylmethyl]-5-methyl-cylopent[4,5]imidao[2, 1-b]purin-49(3H)one (SCH51866) with
      an IC50 of 1.55 microM. This new phosphodiesterase is highly specific for cGMP.
      Its Km of approximately 0.07 microM for cGMP is the lowest yet reported for a
      PDE, being at least 40-170 times lower than that of PDE5 and PDE6, respectively.

PMID- 9624146
TI  - Isolation and characterization of PDE9A, a novel human cGMP-specific
      phosphodiesterase.
AB  - We have cloned and characterized the first human isozyme in a new family of
      cyclic nucleotide phosphodiesterases, PDE9A. By sequence homology in the
      catalytic domain, PDE9A is almost equidistant from all eight known mammalian PDE
      families but is most similar to PDE8A (34% amino acid identity) and least like
      PDE5A (28% amino acid identity). We report the cloning of human cDNA encoding a
      full-length protein of 593 amino acids, including a 261-amino acid region located
      near the C terminus that is homologous to the approximately 270-amino acid
      catalytic domain of other PDEs. PDE9A is expressed in all eight tissues examined
      as a approximately 2. 0-kilobase mRNA, with highest levels in spleen, small
      intestine, and brain. The full-length PDE9A was expressed in baculovirus fused to
      an N-terminal 9-amino acid FLAG tag. Kinetic analysis of the baculovirus
      expressed enzyme shows it to be a very high affinity cGMP-specific PDE with a Km
      of 170 nM for cGMP and 230 microM for cAMP. The Km for cGMP makes PDE9A one of
      the highest affinity PDEs known. The Vmax for cGMP (4.9 nmol/min/microg
      recombinant enzyme) is about twice as fast as that of PDE4 for cAMP. The enzyme
      is about twice as active in vitro in 1-10 mM Mn2+ than in the same concentration
      of Mg2+ or Ca2+. PDE9A is insensitive (up to 100 microM) to a variety of PDE
      inhibitors including rolipram, vinpocetine, SKF-94120, dipyridamole, and 3
      isobutyl-1-methyl-xanthine but is inhibited (IC50 = 35 microM) by zaprinast, a
      PDE5 inhibitor. PDE9A lacks a region homologous to the allosteric cGMP-binding
      regulatory regions found in the cGMP-binding PDEs: PDE2, PDE5, and PDE6.

PMID- 9624147
TI  - Structures of apurinic and apyrimidinic sites in duplex DNAs.
AB  - Natural and exogenous processes can give rise to abasic sites with either a
      purine or pyrimidine as the base on the opposing strand. The solution state
      structures of the apyrimidinic DNA duplex, with D6 indicating an abasic site,
      [sequence: see text] referred to as AD, and the apurinic DNA duplex with a dC17,
      referred to as CD, have been determined. A particularly striking difference is
      that the abasic site in CD is predominantly a beta hemiacetal, whereas in AD the
      alpha and beta forms are equally present. Hydrogen bonding with water by the
      abasic site and the base on the opposite strand appears to play a large role in
      determining the structure near the damaged site. Comparison of these structures
      with that of a duplex DNA containing a thymine glycol at the same position as the
      abasic site and with that of a duplex DNA containing an abasic site in the middle
      of a curved DNA sequence offers some insight into the common and distinct
      structural features of damaged DNA sites.

PMID- 9624148
TI  - Human translocation liposarcoma-CCAAT/enhancer binding protein (C/EBP) homologous
      protein (TLS-CHOP) oncoprotein prevents adipocyte differentiation by directly
      interfering with C/EBPbeta function.
AB  - Human translocation liposarcoma (TLS)-CCAAT/enhancer binding protein (C/EBP)
      homologous protein (CHOP) is a fusion oncoprotein found specifically in a
      malignant tumor of adipose tissue and results from a t(12;16) translocation that
      fuses the amino-terminal part of TLS to the entire coding region of CHOP. Being
      that CHOP is a member of the C/EBP transcription factor family, proteins that
      comprise part of the adipocyte differentiation machinery, we examined whether TLS
      CHOP blocked adipocyte differentiation by directly interfering with C/EBP
      function. Using a single-step retroviral infection protocol, either wild-type or
      mutant TLS-CHOP were co-expressed along with C/EBPbeta in naive NIH3T3 cells, and
      their ability to inhibit C/EBPbeta-driven adipogenesis was determined. TLS-CHOP
      was extremely effective at blocking adipocyte differentiation when expressed at a
      level comparable to that observed in human myxoid liposarcoma. This effect of TLS
      CHOP required a functional leucine zipper domain and correlated with its ability
      to heterodimerize with C/EBPbeta and inhibit C/EBPbeta DNA binding and
      transactivation activity in situ. In contrast, the TLS-CHOP basic region was
      dispensable, making it unlikely that the inhibitory effect of TLS-CHOP is
      attributable to unscheduled gene expression resulting from TLS-CHOP's putative
      transactivation activity. Another adipogenic transcription factor, PPARgamma2,
      was able to rescue TLS-CHOP-inhibited cells, indicating that TLS-CHOP interferes
      primarily with C/EBPbeta-driven adipogenesis and not with other requisite events
      of the adipocyte differentiation program. Together, the results demonstrate that
      TLS-CHOP blocks adipocyte differentiation by directly preventing C/EBPbeta from
      binding to and transactivating its target genes. Moreover, they provide strong
      support for the thesis that a blockade to normal differentiation is an important
      aspect of the cancer process.

PMID- 9624149
TI  - Mapping the serpin-proteinase complex using single cysteine variants of alpha1
      proteinase inhibitor Pittsburgh.
AB  - To probe the covalent serpin-proteinase complex, we used wild-type and 4 new
      single cysteine variants (T85C, S121C, D159C, and D298C) of alpha1-proteinase
      inhibitor Pittsburgh. Cysteines in each variant could be labeled both in native
      and proteinase-complexed alpha1-proteinase inhibitors. Pre-reaction with 7
      nitrobenz-2-oxa-1, 3-diazole-chloride or fluorescein prevented complex formation
      only with the D298C variant. Label at Cys121 greatly increased the stoichiometry
      of inhibition for thrombin and gave an emission spectrum that discriminated
      between native, cleaved, and proteinase-complexed serpin and between complexes
      with trypsin and thrombin, whereas fluorophore at residue 159 on helix F was
      almost insensitive to complex formation. Fluorescence resonance energy transfer
      measurements for covalent and non-covalent complexes were consistent with a
      location of the proteinase at the end of the serpin distal from the original
      location of the reactive center loop. Taken together, these findings are
      consistent with a serpin-proteinase complex in which the reactive center loop is
      fully inserted into beta-sheet A, and the proteinase is at the far end of the
      serpin from its initial site of docking with the reactive center loop close to,
      but not obscuring, residue 121.

PMID- 9624150
TI  - Type XIII collagen is identified as a plasma membrane protein.
AB  - The complete primary structure of the mouse type XIII collagen chain was
      determined by cDNA cloning. Comparison of the mouse amino acid sequences with the
      previously determined human sequences revealed a high identity of 90%.
      Surprisingly, the mouse cDNAs extended further in the 5' direction than the
      previously identified human clones. The 5' sequences contained a new in-frame ATG
      codon for translation initiation which resulted in elongation of the N-terminal
      noncollagenous domain by 81 residues. These N-terminal sequences lack a typical
      signal sequence but include a highly hydrophobic segment that clearly fulfills
      the criteria for a transmembrane domain. The sequence data thus unexpectedly
      suggested that type XIII collagen may be located on the plasma membrane, with a
      short cytosolic N-terminal portion and a long collagenous extracellular portion.
      These sequence data prompted us to generate antipeptide antibodies against type
      XIII collagen in order to study the protein and its subcellular location. Western
      blotting of human tumor HT-1080 cell extract revealed bands of over 180 kDa.
      These appeared to represent disulfide-bonded multimeric polypeptide forms that
      resolved upon reduction into 85-95-kDa bands that are likely to represent a
      mixture of splice forms of monomeric type XIII collagen chains. These chains were
      shown to contain the predicted N-terminal extension and thus also the putative
      transmembrane segment. Immunoprecipitation of biotinylated type XIII collagen
      from surface-labeled HT-1080 cells, subcellular fractionation, and
      immunofluorescence staining were used to demonstrate that type XIII collagen
      molecules are indeed located in the plasma membranes of these cells.

PMID- 9624151
TI  - Inhibition of the self-assembly of collagen I into fibrils with synthetic
      peptides. Demonstration that assembly is driven by specific binding sites on the
      monomers.
AB  - A series of experiments were carried out to test the hypothesis that the self
      assembly of collagen I monomers into fibrils depends on the interactions of
      specific binding sites in different regions of the monomer. Six synthetic
      peptides were prepared with sequences found either in the collagen triple helix
      or in the N- or C-telopeptides of collagen I. The four peptides with sequences
      found in the telopeptides were found to inhibit self-assembly of collagen I in a
      purified in vitro system. At concentrations of 2.5 mM, peptides with sequences in
      the C-telopeptides of the alpha1(I) and alpha2(I) chain inhibited assembly at
      about 95%. The addition of the peptide with the alpha2-telopeptide sequence was
      effective in inhibiting assembly if added during the lag phase and early
      propagation phase but not later in the assembly process. Experiments with
      biotinylated peptides indicated that both the N- and C-telopeptides bound to a
      region between amino acid 776 and 822 of the alpha(I) chain. A fragment of nine
      amino acids with sequences in the alpha2-telopeptide was effective in inhibiting
      fibril assembly. Mutating two aspartates in the 9-mer peptide to serine had no
      effect on inhibition of fibril assembly, but mutating two tyrosine residues and
      one phenylalanine residue abolished the inhibitory action. Molecular modeling of
      the binding sites demonstrated favorable hydrophobic and electrostatic
      interactions between the alpha2telopeptide and residues 781-794 of the alpha(I)
      chain.

PMID- 9624152
TI  - Acquisition of sensitivity of stress-activated protein kinases to the p38
      inhibitor, SB 203580, by alteration of one or more amino acids within the ATP
      binding pocket.
AB  - Pyridinyl imidazole inhibitors of p38 mitogen-activated protein kinase compete
      with ATP for binding. Mutation of 23 residues in the ATP pocket indicated that
      several residues which affected binding of pyridinyl imidazole photoaffinity
      cross-linker 125I-SB 206718 did not affect kinase activity, and vice versa,
      suggesting that pyridinyl imidazoles bind p38 differently than ATP. Two close
      homologues of p38, SAPK3 and SAPK4, are not inhibited by SB 203580 and differ
      from p38 by three amino acids near the hinge of the ATP pocket. Substitution of
      the three amino acids in p38 by those in SAPK3/4 (Thr-106, His-107, and Leu-108
      to Met, Pro, and Phe) resulted in decreased 125I-SB 206718 cross-linking and loss
      of inhibition by SB 203580. Substitution of just Thr-106 by Met resulted in
      incomplete loss of inhibition. Conversely, substitution of the three amino acids
      of p38 into SAPK3, SAPK4, or the more distantly related JNK1 resulted in
      inhibition by SB 203580, whereas mutation of just Met-106 to Thr resulted in
      weaker inhibition. These results indicate that these three amino acids can confer
      specificity and sensitivity to SB 203580 for at least two different classes of
      MAPKs.

PMID- 9624153
TI  - Liprins, a family of LAR transmembrane protein-tyrosine phosphatase-interacting
      proteins.
AB  - LAR family transmembrane protein-tyrosine phosphatases function in axon guidance
      and mammary gland development. In cultured cells, LAR binds to the intracellular,
      coiled coil LAR-interacting protein at discrete ends of focal adhesions,
      implicating these proteins in the regulation of cell-matrix interactions. We
      describe seven LAR-interacting protein-like genes in humans and Caenorhabditis
      elegans that form the liprin gene family. Based on sequence similarities and
      binding characteristics, liprins are subdivided into alpha-type and beta-type
      liprins. The C-terminal, non-coiled coil regions of alpha-liprins bind to the
      membrane-distal phosphatase domains of LAR family members, as well as to the C
      terminal, non-coiled coil region of beta-liprins. Both alpha- and beta-liprins
      homodimerize via their N-terminal, coiled coil regions. Liprins are thus
      multivalent proteins that potentially form complex structures. Some liprins have
      broad mRNA tissue distributions, whereas others are predominately expressed in
      the brain. Co-expression studies indicate that liprin-alpha2 alters LAR cellular
      localization and induces LAR clustering. We propose that liprins function to
      localize LAR family tyrosine phosphatases at specific sites on the plasma
      membrane, possibly regulating their interaction with the extracellular
      environment and their association with substrates.

PMID- 9624154
TI  - Cationic liposomes coated with polyethylene glycol as carriers for
      oligonucleotides.
AB  - Modification of liposome surface with polyethylene glycol was used to improve
      oligodeoxyribonucleotide (ODN) loading, stability of the resulting complexes, and
      specificity of cellular delivery of ODN by cationic liposomes. Liposomes composed
      of a cationic lipid (DOTAP, DOGS, DDAB), a neutral lipid (DOPE), and a
      phospholipid derivative of polyethylene glycol (PEG-PE) formed a complex with 18
      mer phosphorothioate up to ODN/lipid molar ratio of 0.25. The complexes showed
      intact vesicular structures similar to original liposomes and their size (100-130
      nm) was unchanged after several weeks of storage, whereas complexes lacking PEG
      PE showed progressive aggregation and/or precipitation. After exposure to human
      plasma, PEG-modified cationic liposomes retained over 60% of the originally bound
      ODN. PEG-coated complexes resulted in 4-13-fold enhancement of the ODN uptake by
      human breast cancer cells in serum-supplemented growth medium, relative to free
      ODN. Complexes containing conjugated anti-HER2 F(ab') fragments at the distal
      termini of PEG chains efficiently delivered ODN primarily into the cytoplasm and
      nuclei of HER2 overexpressing cancer cells and greatly enhanced the biological
      activity of antisense ODN. The development of PEG-modified cationic liposomes may
      lead to improved ODN potency in vivo.

PMID- 9624155
TI  - Dissociation of phagocyte recognition of cells undergoing apoptosis from other
      features of the apoptotic program.
AB  - Apoptosis is a programmed form of cell death characterized by biochemical and
      morphological changes affecting the nucleus, cytoplasm, and plasma membrane.
      These changes in various cellular compartments are widely regarded as
      mechanistically linked events in a single "program" in which activation of
      caspases and proteolysis of intracellular substrates represent a final common
      pathway leading to cell death. To date there has been very limited exploration of
      the linkage of this program to the plasma membrane changes, which bring about
      swift recognition, uptake, and safe degradation of apoptotic cells by phagocytes.
      Using the mitochondrial inhibitors antimycin A and oligomycin in human monocytic
      THP.1 cells triggered into apoptosis, we report the uncoupling of plasma membrane
      changes from other features of apoptosis. These inhibitors blocked increased
      plasma membrane permeability, externalization of phosphatidylserine, and
      recognition by two classes of phagocytes but not activation of caspase-3,
      cleavage of poly(ADP-ribose) polymerase and DNA fragmentation. Externalization of
      phosphatidylserine in apoptotic human leukemic U937 cells was also dissociated
      from caspase activation. Thus changes governing safe clearance of apoptotic cells
      may be regulated by an independent pathway to those bringing about caspase
      activation. This finding could have important consequences for attempts to
      manipulate cell death for therapeutic gain in vivo.

PMID- 9624156
TI  - Solution structure and main chain dynamics of the regulatory domain (Residues 1
      91) of human cardiac troponin C.
AB  - The three-dimensional structure of calcium-loaded regulatory, i.e. N-terminal,
      domain (1-91) of human cardiac troponin C (cNTnC) was determined by NMR in
      water/trifluoroethanol (91:9 v/v) solution. The single-calcium-loaded cardiac
      regulatory domain is in a "closed" conformation with comparatively little exposed
      hydrophobic surface. Difference distance matrices computed from the families of
      Ca2+-cNTnC, the apo and two-calcium forms of the skeletal TnC (sNTnC) structures
      reveal similar relative orientations for the N, A, and D helices. The B and C
      helices are closer to the NAD framework in Ca2+-cNTnC and in apo-sNTnC than in
      2.Ca2+-sNTnC. However, there is an indication of a conformational exchange based
      on broad 15N resonances for several amino acids measured at several temperatures.
      A majority of the amides in the alpha-helices and in the calcium binding loop
      exhibit very fast motions with comparatively small amplitudes according to the
      Lipari-Szabo model. A few residues at the N and C termini are flexible. Data were
      recorded from nonlabeled and 15N-labeled samples, and backbone dynamics was
      investigated by 15N T1, T2, and heteronuclear nuclear Overhauser effect as well
      as by relaxation interference measurements.

PMID- 9624157
TI  - Steatohepatitis, spontaneous peroxisome proliferation and liver tumors in mice
      lacking peroxisomal fatty acyl-CoA oxidase. Implications for peroxisome
      proliferator-activated receptor alpha natural ligand metabolism.
AB  - Peroxisomal beta-oxidation system consists of four consecutive reactions to
      preferentially metabolize very long chain fatty acids. The first step of this
      system, catalyzed by acyl-CoA oxidase (AOX), converts fatty acyl-CoA to 2-trans
      enoyl-CoA. Herein, we show that mice deficient in AOX exhibit steatohepatitis,
      increased hepatic H2O2 levels, and hepatocellular regeneration, leading to a
      complete reversal of fatty change by 6 to 8 months of age. The liver of AOX-/-
      mice with regenerated hepatocytes displays profound generalized spontaneous
      peroxisome proliferation and increased mRNA levels of genes that are regulated by
      peroxisome proliferator-activated receptor alpha (PPARalpha). Hepatic adenomas
      and carcinomas develop in AOX-/- mice by 15 months of age due to sustained
      activation of PPARalpha. These observations implicate acyl-CoA and other putative
      substrates for AOX, as biological ligands for PPARalpha; thus, a normal AOX gene
      is indispensable for the physiological regulation of PPARalpha.

PMID- 9624158
TI  - Characterization of the cytoprotective action of peroxynitrite decomposition
      catalysts.
AB  - The formation of the powerful oxidant peroxynitrite (PN) from the reaction of
      superoxide anion with nitric oxide has been shown to be a kinetically favored
      reaction contributing to cellular injury and death at sites of tissue
      inflammation. The PN molecule is highly reactive causing lipid peroxidation as
      well as nitration of both free and protein-bound tyrosine. We present evidence
      for the pharmacological manipulation of PN with decomposition catalysts capable
      of converting it to nitrate. In target cells challenged with exogenously added
      synthetic PN, a series of metalloporphyrin catalysts (5,10,15,20-tetrakis(2,4,6
      trimethyl-3, 3-disulfonatophenyl)porphyrinato iron (III) (FeTMPS); 5,10,15, 20
      tetrakis(4-sulfonatophenyl)porphyrinato iron (III) (FeTPPS); 5,10, 15,20
      tetrakis(N-methyl-4'-pyridyl)porphyrinato iron (III) (FeTMPyP)) provided
      protection against PN-mediated injury with EC50 values for each compound 30-50
      fold below the final concentration of PN added. Cytoprotection was correlated
      with a reduction in the level of measurable nitrotyrosine. In addition, we found
      our catalysts to be cytoprotective against endogenously generated PN in endotoxin
      stimulated RAW 264.7 cells as well as in dissociated cultures of hippocampal
      neurons and glia that had been exposed to cytokines. Our studies thus provide
      compelling evidence for the involvement of peroxynitrite in cytokine-mediated
      cellular injury and suggest the therapeutic potential of PN decomposition
      catalysts in reducing cellular damage at sites of inflammation.

PMID- 9624159
TI  - Aortic carboxypeptidase-like protein, a novel protein with discoidin and
      carboxypeptidase-like domains, is up-regulated during vascular smooth muscle cell
      differentiation.
AB  - Phenotypic modulation of vascular smooth muscle cells plays an important role in
      the pathogenesis of arteriosclerosis. In a screen of proteins expressed in human
      aortic smooth muscle cells, we identified a novel gene product designated aortic
      carboxypeptidase-like protein (ACLP). The approximately 4-kilobase human cDNA and
      its mouse homologue encode 1158 and 1128 amino acid proteins, respectively, that
      are 85% identical. ACLP is a nonnuclear protein that contains a signal peptide, a
      lysine- and proline-rich 11-amino acid repeating motif, a discoidin-like domain,
      and a C-terminal domain with 39% identity to carboxypeptidase E. By Western blot
      analysis and in situ hybridization, we detected abundant ACLP expression in the
      adult aorta. ACLP was expressed predominantly in the smooth muscle cells of the
      adult mouse aorta but not in the adventitia or in several other tissues. In
      cultured mouse aortic smooth muscle cells, ACLP mRNA and protein were up
      regulated 2-3-fold after serum starvation. Using a recently developed neural
      crest cell to smooth muscle cell in vitro differentiation system, we found that
      ACLP mRNA and protein were not expressed in neural crest cells but were up
      regulated dramatically with the differentiation of these cells. These results
      indicate that ACLP may play a role in differentiated vascular smooth muscle
      cells.

PMID- 9624160
TI  - Evidence for a new type of outer membrane lipid in oral spirochete Treponema
      denticola. Functioning permeation barrier without lipopolysaccharides.
AB  - A new class of outer membrane lipid (OML) was isolated from the oral spirochete
      Treponema denticola strain ATCC 33521 using a phenol/chloroform/light petroleum
      procedure normally applied for lipopolysaccharide extraction. In addition to
      chemical analysis, Fourier transform infrared (FTIR) spectroscopy was applied to
      compare the biophysical properties of OML with lipopolysaccharides (LPS) and
      lipoteichoic acids (LTA). Isolated OML fractions represent 1.4% of the total dry
      cell weight, are about 4 kDa in size, and contain 6% amino sugars, 8% neutral
      sugars, 14% phosphate, 35% carbazol-positive compounds, and 11% fatty acids
      (containing iso- and anteiso-fatty acyl chains). Rare for outer membrane lipids,
      OML contains no significant amount of 3-deoxy-D-manno-octulosonic acids,
      heptoses, and beta-hydroxy fatty acids. The fatty acyl chain composition, being
      similar to that of the cytoplasmic membrane, is quite heterogeneous with anteiso
      pentadecanoic acid (12%), palmitic acid (51%), and iso-palmitic acid (19%) as the
      predominant fatty acids present. Findings of a glycerol-hexose unit and two
      glycerol-hexadecanoic acid fragments indicate a glycolipid membrane anchor
      typically found in LTA. There was also no evidence for the presence of a
      sphingosine-based lipid structure. The results of FTIR measurements strongly
      suggest that the reconstituted lipid forms normal bilayer structures (vesicles)
      expressing a high membrane state of order with a distinct phase transition as
      typical for isolated LPS. However, in contrast to LPS, OML of T. denticola has a
      lower Tm near 22 degreesC and a lower cooperativity of the phase transition. The
      results suggest a different kind of permeation barrier that is built up by this
      particular OML of T. denticola, which is quite different from LPS normally
      essential for Gram-negative bacteria.

PMID- 9624161
TI  - alpha-conotoxin EpI, a novel sulfated peptide from Conus episcopatus that
      selectively targets neuronal nicotinic acetylcholine receptors.
AB  - We have isolated and characterized alpha-conotoxin EpI, a novel sulfated peptide
      from the venom of the molluscivorous snail, Conus episcopatus. The peptide was
      classified as an alpha-conotoxin based on sequence, disulfide connectivity, and
      pharmacological target. EpI has homology to sequences of previously described
      alpha-conotoxins, particularly PnIA, PnIB, and ImI. However, EpI differs from
      previously reported conotoxins in that it has a sulfotyrosine residue, identified
      by amino acid analysis and mass spectrometry. Native EpI was shown to coelute
      with synthetic EpI. The peptide sequence is consistent with most, but not all,
      recognized criteria for predicting tyrosine sulfation sites in proteins and
      peptides. The activities of synthetic EpI and its unsulfated analogue [Tyr15]EpI
      were similar. Both peptides caused competitive inhibition of nicotine action on
      bovine adrenal chromaffin cells (neuronal nicotinic ACh receptors) but had no
      effect on the rat phrenic nerve-diaphragm (muscle nicotinic ACh receptors). Both
      EpI and [Tyr15]EpI partly inhibited acetylcholine-evoked currents in isolated
      parasympathetic neurons of rat intracardiac ganglia. These results indicate that
      EpI and [Tyr15]EpI selectively inhibit alpha3beta2 and alpha3 beta4 nicotinic
      acetylcholine receptors.

PMID- 9624162
TI  - A revised model for the oligomeric state of the N-ethylmaleimide-sensitive fusion
      protein, NSF.
AB  - The N-ethylmaleimide-sensitive fusion protein (NSF) is an ATPase that plays an
      essential role in intracellular membrane trafficking. Previous reports have
      concluded that NSF forms either a tetramer or a trimer in solution, and that
      assembly of the oligomer is essential for efficient activity in membrane
      transport reactions. However, in recent electron microscopic analyses NSF appears
      as a hexagonal cylinder similar in size to related ATPases known to be hexamers.
      We have therefore reevaluated NSF's oligomeric state using a variety of
      quantitative biophysical techniques. Sedimentation equilibrium and sedimentation
      velocity analytical ultracentrifugation, transmission electron microscopy with
      rotational image analysis, scanning transmission electron microscopy, and
      multiangle light scattering all demonstrate that, in the presence of nucleotide,
      NSF is predominantly a hexamer. Sedimentation equilibrium results further suggest
      that the NSF hexamer is held together by oligomerization of its D2 domains. The
      sedimentation coefficient, s20,w0, of 13.4 (+/-0. 1) S indicates that NSF has
      unusual hydrodynamic characteristics that cannot be solely explained by its
      shape. The demonstration that NSF is a hexameric oligomer highlights structural
      similarities between it and several related ATPases which act by switching the
      conformational states of their protein substrates in order to activate them for
      subsequent reactions.

PMID- 9624163
TI  - Base orientation of second DNA in RecA.DNA filaments. Analysis by combination of
      linear dichroism and small angle neutron scattering in flow-oriented solution.
AB  - To gain insight into the mechanism of pairing two complementary DNA strands by
      the RecA protein, we have determined the nucleobase orientation of the first and
      the second bound DNA strands in the RecA.DNA filament by combined measurements of
      linear dichroism and small angle neutron scattering on flow-oriented samples. An
      etheno-modified DNA, poly(depsilonA) was adapted as the first DNA and an
      oligo(dT) as the second DNA, making it possible to distinguish between the linear
      dichroism signals of the two DNA strands. The results indicate that binding of
      the second DNA does not alter the nucleobase orientation of the first bound
      strand and that the bases of the second DNA are almost coplanar to the bases of
      the first strand although somewhat more tilted (60 degrees relative to the fiber
      axis compared with 70 degrees for the first DNA strand). Similar results were
      obtained for the RecA.DNA complex formed with unmodified poly(dA) and oligo(dT).
      An almost coplanar orientation of nucleobases of two DNA strands in a RecA-DNA
      filament would facilitate scanning for, and recognition of, complementary base
      sequences. The slight deviation from co-planarity could increase the free energy
      of the duplex to facilitate dissociation in case of mismatching base sequences.

PMID- 9624164
TI  - Identification and characterization of small molecule functional antagonists of
      the CCR1 chemokine receptor.
AB  - The CC chemokines macrophage inflammatory protein-1alpha (MIP-1alpha) and RANTES
      (regulated on activation normal T cell expressed) have been implicated in
      rheumatoid arthritis and multiple sclerosis. Since their effects are mediated
      through the CCR1 chemokine receptor, we set up a small molecule CCR1 antagonist
      program to search for inhibitors. Through high capacity screening we discovered a
      number of 4-hydroxypiperidine compounds with CCR1 antagonist activity and report
      their synthesis and in vitro pharmacology here. Scatchard analysis of the
      competition binding data revealed that the compounds had Ki values ranging from
      40 to 4000 nM. The pharmacological profile of the most potent member of this
      series, compound 1 (2-2-diphenyl-5-(4-chlorophenyl)piperidin-lyl)valeronitri te),
      was further evaluated. Compound 1 showed concentration-dependent inhibition of
      MIP-1alpha-induced extracellular acidification and Ca2+ mobilization
      demonstrating functional antagonism. When given alone, the compound did not
      elicit any responses, indicating the absence of intrinsic agonist activity.
      Compound 1 inhibited MIP-1alpha- and RANTES-induced migration in peripheral blood
      mononuclear cells in a dose-responsive manner. Selectivity testing against a
      panel of seven transmembrane domain receptors indicated that compound 1 is
      inactive on a number of receptors at concentrations up to 10 microM. This is the
      first description of CCR1 receptor antagonists that may be useful in the
      treatment of chronic inflammatory diseases involving MIP-1alpha, RANTES, and
      CCR1.

PMID- 9624165
TI  - Cryptic Rac-binding and p21(Cdc42Hs/Rac)-activated kinase phosphorylation sites
      of NADPH oxidase component p67(phox).
AB  - Rac1 is a member of the Rho family of small molecular mass GTPases that act as
      molecular switches to control actin-based cell morphology as well as cell growth
      and differentiation. Rac1 and Rac2 are specifically required for superoxide
      formation by components of the NADPH oxidase. In binding assays, Rac1 interacts
      directly with p67(phox), but not with the other oxidase components: cytochrome b,
      p40(phox), or p47(phox) (Prigmore, E., Ahmed, S., Best, A., Kozma, R. , Manser,
      E., Segal, A. W., and Lim, L. (1995) J. Biol. Chem. 270, 10717-10722). Here, the
      Rac1/2 interaction with p67(phox) has been characterized further. Rac1 and Rac2
      can bind to p67(phox) amino acid residues 170-199, and the N terminus (amino
      acids 1-192) of p67(phox) can be used as a specific inhibitor of Rac signaling.
      Deletion of p67(phox) C-terminal sequences (amino acids 193-526), the C-terminal
      SH3 domain (amino acids 470-526), or the polyproline-rich motif (amino acids 226
      236) stimulates Rac1 binding by approximately 8-fold. p21(Cdc42Hs/Rac)-activated
      kinase (PAK) phosphorylates p67(phox) amino acid residues adjacent to the Rac1/2
      binding site, and this phosphorylation is stimulated by deletion of the C
      terminal SH3 domain or the polyproline-rich motif. These data suggest a role for
      cryptic Rac-binding and PAK phosphorylation sites of p67(phox) in control of the
      NADPH oxidase.

PMID- 9624166
TI  - ERICE, a novel FLICE-activatable caspase.
AB  - Programmed cell death, or apoptosis, is a process of fundamental importance to
      cellular homeostasis in metazoan organisms (Ellis, R. E., Yuan, J., and Horvitz,
      H. R. (1991) Annu. Rev. Cell Biol. 7, 663-698). The caspase family of mammalian
      proteases, related to the nematode death protein CED-3, plays a crucial role in
      apoptosis and inflammation. We report here the isolation and characterization of
      a new caspase, tentatively termed ERICE (Evolutionarily Related Interleukin-1beta
      Converting Enzyme). Based on phylogenetic analysis, ERICE (caspase-13) is a
      member of the ICE subfamily of caspases which includes caspase-1 (ICE), caspase-4
      (ICErel-II, TX, ICH-2), and caspase-5 (ICErel-III, TY). Overexpression of ERICE
      induces apoptosis of 293 human embryonic kidney cells and MCF7 breast carcinoma
      cells. Like other members of the subfamily, ERICE is not activated by the serine
      protease granzyme B, a caspase-activating component of cytotoxic T cell granules.
      Therefore, ERICE most likely does not play a role in granzyme B-induced cell
      death. ERICE, however, was activated by caspase-8 (FLICE, MACH, Mch-5), the
      apical caspase activated upon engagement of death receptors belonging to the
      tumor necrosis factor family. This is consistent with a potential role for ERICE
      in this receptor-initiated death pathway.

PMID- 9624167
TI  - Collapsin-1 covalently dimerizes, and dimerization is necessary for collapsing
      activity.
AB  - Chick collapsin-1, the first identified vertebrate member of the semaphorin
      family of axon guidance proteins, repels specific growth cones. Like all family
      members, collapsin-1 contains within its sequence a semaphorin domain that is
      necessary for specifying activity. Two additional structural domains of collapsin
      1, the immunoglobulin (Ig) domain and the basic tail, each potentiate collapsin-1
      activity. We identify in this study another structural feature of collapsin-1
      that is necessary for its function. Collapsin-1 covalently dimerizes, and
      dimerization is necessary for collapse activity. This dimerization is mediated
      through a cysteine at residue 723, between the Ig domain and basic tail. The
      semaphorin domain alone is not active since it cannot dimerize. The collapsing
      activity of the semaphorin domain can be reconstituted when made as a chimeric
      construct with an immunoglobin Fc domain, which promotes dimerization.

PMID- 9624168
TI  - Expression of plasma phospholipid transfer protein mRNA in normal and
      emphysematous lungs and regulation by hypoxia.
AB  - The lung is the major site expressing plasma phospholipid transfer protein (PLTP)
      mRNA in humans and mice, suggesting that this protein might have an important
      role in maintaining normal function of this organ. In the lung of human
      collagenase transgenic mice, an emphysematous animal model, PLTP mRNA was 3-fold
      higher than in control mice. However, the mRNA in other tissues was not changed.
      To further assess the expression and function of PLTP, we measured PLTP mRNA
      level in lung tissue of two emphysematous patients and found that the mRNA was 4
      fold higher than in control subjects. In situ hybridization on mouse lung
      suggested positive staining in alveolar type II epithelial cells. In addition,
      immortalized rat alveolar pre-type II epithelial cells and freshly isolated
      mature rat alveolar type II epithelial cells both highly expressed PLTP mRNA, and
      the former cells actively secreted PLTP activity into the medium. To examine the
      possible mechanisms leading to high levels of PLTP expression in vivo, we exposed
      the pre-type II cells to hypoxia and demonstrated induction of PLTP mRNA and a
      coordinate increase in secreted PLTP activity. Thus, the PLTP gene is highly
      expressed in alveolar type II epithelial cells and is induced during hypoxia and
      in emphysema. These observations suggest that a hypoxic stimulus occurring in
      emphysema may be a novel mechanism that contributes to enhanced expression of
      PLTP.

PMID- 9624169
TI  - Growth hormone and prolactin stimulate tyrosine phosphorylation of insulin
      receptor substrate-1, -2, and -3, their association with p85 phosphatidylinositol
      3-kinase (PI3-kinase), and concomitantly PI3-kinase activation via JAK2 kinase.
AB  - Growth hormone (GH) and prolactin (PRL) binding to their receptors, which belong
      to the cytokine receptor superfamily, activate Janus kinase (JAK) 2 tyrosine
      kinase, thereby leading to their biological actions. We recently showed that GH
      mainly stimulated tyrosine phosphorylation of epidermal growth factor receptor
      and its association with Grb2, and concomitantly stimulated mitogen-activated
      protein kinase activity in liver, a major target tissue. Using specific
      antibodies, we now show that GH was also able to induce tyrosine phosphorylation
      of insulin receptor substrate (IRS)-1/IRS-2 in liver. In addition, the major
      tyrosine-phosphorylated protein in anti-p85 phosphatidylinositol 3-kinase (PI3
      kinase) immunoprecipitate from liver of wild-type mice was IRS-1, and IRS-2 in
      IRS-1 deficient mice, but not epidermal growth factor receptor. These data
      suggest that tyrosine phosphorylation of IRS-1 may be a major mechanism for GH
      induced PI3-kinase activation in physiological target organ of GH, liver. We also
      show that PRL was able to induce tyrosine phosphorylation of both IRS-1 and IRS-2
      in COS cells transiently transfected with PRLR and in CHO-PRLR cells. Moreover,
      we show that tyrosine phosphorylation of IRS-3 was induced by both GH and PRL in
      COS cells transiently transfected with IRS-3 and their cognate receptors. By
      using the JAK2-deficient cell lines or by expressing a dominant negative JAK2
      mutant, we show that JAK2 is required for the GH- and PRL-dependent tyrosine
      phosphorylation of IRS-1, -2, and -3. Finally, a specific PI3-kinase inhibitor,
      wortmannin, completely blocked the anti-lipolytic effect of GH in 3T3 L1
      adipocytes. Taken together, the role of IRS-1, -2, and -3 in GH and PRL
      signalings appears to be phosphorylated by JAK2, thereby providing docking sites
      for p85 PI3-kinase and activating PI3-kinase and its downstream biological
      effects.

PMID- 9624170
TI  - Binding of c-Raf1 kinase to a conserved acidic sequence within the carboxyl
      terminal region of the HIV-1 Nef protein.
AB  - Nef is a membrane-associated cytoplasmic phosphoprotein that is well conserved
      among the different human (HIV-1 and HIV-2) and simian immunodeficiency viruses
      and has important roles in down-regulating the CD4 receptor and modulating T-cell
      signaling pathways. The ability to modulate T-cell signaling pathways suggests
      that Nef may physically interact with T-cell signaling proteins. In order to
      identify Nef binding proteins and map their site(s) of interaction, we targeted a
      highly conserved acidic sequence at the carboxyl-terminal region of Nef sharing
      striking similarity with an acidic sequence at the c-Raf1-binding site within the
      Ras effector region. Here, we used deletion and site-specific mutagenesis to
      generate mutant Nef proteins fused to bacterial glutathione S-transferase in in
      vitro precipitation assays and immunoblot analysis to map the specific
      interaction between the HIV-1LAI Nef and c-Raf1 to a conserved acidic sequence
      motif containing the core sequence Asp-Asp-X-X-X-Glu (position 174-179).
      Significantly, we demonstrate that substitution of the nonpolar glycine residue
      for either or both of the conserved negatively charged aspartic acid residues at
      positions 174 and 175 in the full-length recombinant Nef protein background
      completely abrogated binding of c-Raf1 in vitro. In addition, lysates from a
      permanent CEM T-cell line constitutively expressing the native HIV-1 Nef protein
      was used to coimmunoprecipitate a stable Nef-c-Raf1 complex, suggesting that
      molecular interactions between Nef and c-Raf1, an important downstream transducer
      of cell signaling through the c-Raf1-MAP kinase pathway, occur in vivo. This
      interaction may account for the Nef-induced perturbations of T-cell signaling and
      activation pathways in vitro and in vivo.

PMID- 9624171
TI  - Rab17 localizes to recycling endosomes and regulates receptor-mediated
      transcytosis in epithelial cells.
AB  - The small GTPase Rab17 is restricted to epithelial cells and its expression is
      induced during cell polarization. This observation has led to the suggestion that
      the protein may function in transcytosis, a pathway connecting the apical and
      basolateral endocytic systems. To analyze whether Rab17 plays a role in
      transcellular transport, we generated Madin-Darby canine kidney (MDCK) cell lines
      stably coexpressing wild-type or mutant Rab17 and the transcytotic polymeric
      immunoglobulin receptor (pIgR). Rab17 expressed in MDCK cells was found on small
      vesicles and tubules in the apical region of the cells. A significant fraction of
      the Rab17-positive structures was accessible to dimeric IgA internalized from the
      apical or basolateral cell surface via the pIgR. Furthermore, basolateral to
      apical transcytosis of dimeric IgA was impaired in MDCK cells overexpressing
      Rab17. Our data provides morphological and biochemical evidence for a role of
      Rab17 in the regulation of transcellular traffic through apical recycling
      endosomes in epithelial cells.

PMID- 9624172
TI  - Differential roles of extracellular signal-regulated kinase-1/2 and p38(MAPK) in
      interleukin-1beta- and tumor necrosis factor-alpha-induced low density
      lipoprotein receptor expression in HepG2 cells.
AB  - The inflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor
      alpha (TNF), elevated in inflammatory, malignant, and infectious diseases, induce
      low density lipoprotein (LDL) receptor transcription in HepG2 cells, and such an
      induction can account for hypocholesterolemia associated with these states.
      However, the signaling mechanisms of cytokine-mediated LDL receptor induction are
      largely unexplored. In the present studies, we examined the potential involvement
      of different mitogen-activated protein kinase (MAPK) pathways. Northern analysis
      demonstrated that IL-1beta or TNF significantly increased LDL receptor transcript
      in HepG2 cells, whereas expression of another tightly regulated sterol-responsive
      squalene synthase gene was unaffected. IL-1beta treatment resulted in transient
      activation of three MAPK cascades, namely p46/54(JNK), p38(MAPK), and ERK-1/2,
      with maximal activation of 20-, 25-, and 3-fold, respectively, occurring 15-30
      min after cytokine addition. PD98059, a specific inhibitor of MAPK kinase
      activity, inhibited IL-1beta-induced LDL receptor expression. In contrast,
      SB202190, a specific inhibitor of p38(MAPK), enhanced IL-1beta-induced LDL
      receptor expression, with a concomitant increase in ERK-1/2 activity. Similarly,
      TNF induced LDL receptor expression also required ERK-1/2 activation. Finally,
      sterols repressed IL-1beta induced receptor expression, without affecting ERK-1/2
      activation. These results show that IL-1beta- or TNF-induced LDL receptor
      expression requires ERK-1/2 activation, that the p38(MAPK) pathway negatively
      regulates LDL receptor expression, and that sterols inhibit induction at a point
      downstream of ERK-1/2 in HepG2 cells.

PMID- 9624173
TI  - c-myc mRNA is down-regulated during myogenic differentiation by accelerated decay
      that depends on translation of regulatory coding elements.
AB  - Murine C2C12 myoblasts induced to differentiate into multinucleated myotubes
      decrease their levels of c-myc mRNA 3-10-fold through posttranscriptional
      mechanisms that recognize regulatory elements contained in protein-coding
      sequences in exons 2 and 3 of the mRNA. To determine the mechanism by which these
      elements mediate c-myc mRNA down-regulation, we examined the regulation of mutant
      MYC and human beta-globin-MYC fusion mRNAs. Regulation of mRNAs containing MYC
      exon 2 or 3 is abolished by insertion of an upstream termination codon indicating
      that regulatory function depends on their translation. Exploiting this
      translation dependence, we show that pharmacologic inhibition of translation with
      cycloheximide abolishes the down-regulation of regulated MYC and globin-MYC mRNAs
      and induces their levels in differentiating C2C12 cells. We exclude the
      possibility that this induction in mRNA levels results from cycloheximide effects
      on transcription or processing of parts of the RNA other than the regulatory
      elements, leading to the conclusion that cycloheximide induction results from
      mRNA stabilization. We show that the magnitude of cycloheximide induction can be
      used to estimate turnover rates of mRNAs whose decay is translation-dependent. By
      using cycloheximide inducibility to examine turnover rates of MYC and globin-MYC
      mRNAs, we show that the MYC exon 2 and exon 3 regulatory elements, but not MYC 3'
      untranslated region or chloramphenicol acetyltransferase coding sequences,
      mediate accelerated mRNA decay in differentiating, but not undifferentiated,
      C2C12 cells. We show that these regulatory elements must be translated to confer
      accelerated mRNA decay and that increased turnover occurs in the cytoplasm and
      not in the nucleus. Finally, using cycloheximide induction to examine mRNA half
      lives, we show that mRNA turnover is increased sufficiently by mechanisms
      targeting the exon 2 and 3 regulatory elements to account for the magnitude of c
      myc mRNA down-regulation during differentiation. We conclude from these results
      that c-myc mRNA down-regulation during myogenic differentiation is due to
      translation-dependent mechanisms that target mRNAs containing myc exon 2 and 3
      regulatory elements for accelerated decay.

PMID- 9624174
TI  - Versican V2 is a major extracellular matrix component of the mature bovine brain.
AB  - We have isolated and characterized the proteoglycan isoforms of versican from
      bovine brain extracts. Our approach included (i) cDNA cloning and sequencing of
      the entire open reading frame encoding the bovine versican splice variants; (ii)
      preparation of antibodies against bovine versican using recombinant core protein
      fragments and synthetic peptides; (iii) isolation of versican isoforms by
      ammonium sulfate precipitation followed by anion exchange and hyaluronan affinity
      chromatography; and (iv) characterization by SDS-polyacrylamide gel
      electrophoresis and Coomassie Blue staining or immunoblotting. Our results
      demonstrate that versican V2 is, together with brevican, a major component of the
      mature brain extracellular matrix. Versicans V0 and V1 are only present in
      relatively small amounts. Versican V2 migrates after chondroitinase ABC digestion
      with an apparent molecular mass of about 400 kDa, whereas it barely enters a 4
      15% polyacrylamide gel without the enzyme treatment. The 400-kDa product is
      recognized by antibodies against the glycosaminoglycan-alpha domain and against
      synthetic NH2- and COOH-terminal peptides. Our preparations contain no major
      proteolytic products of versican, e.g. hyaluronectin or glial hyaluronate-binding
      protein. Having biochemical quantities of versican V2 available will allow us to
      test its putative modulatory role in neuronal cell adhesion and axonal growth.

PMID- 9624175
TI  - Regulation of mouse PECAM-1 tyrosine phosphorylation by the Src and Csk families
      of protein-tyrosine kinases.
AB  - PECAM-1 is an adhesion molecule expressed on hemopoietic and endothelial cells.
      Recently, it was observed that PECAM-1 becomes tyrosine-phosphorylated in
      response to a variety of physiological stimuli. Furthermore, tyrosine
      phosphorylated PECAM-1 was shown to associate with SHP-2, a Src homology 2 (SH2)
      domain-containing protein-tyrosine phosphatase expressed ubiquitously. In light
      of the significance of tyrosine protein phosphorylation as a regulatory
      mechanism, we wished to understand better the nature and impact of the protein
      tyrosine kinases (PTKs) mediating PECAM-1 tyrosine phosphorylation. Through
      reconstitution experiments in COS-1 cells, we determined that mouse PECAM-1 could
      be tyrosine-phosphorylated by Src-related PTKs and Csk-related PTKs, but not by
      other kinases such as Syk, Itk, and Pyk2. Using site-directed mutagenesis and
      peptide phosphorylation studies, we found that these PTKs were efficient at
      phosphorylating Tyr-686, but not Tyr-663, of PECAM-1. Src-related enzymes also
      phosphorylated mouse PECAM-1 at one or more yet to be identified sites. In other
      studies, we demonstrated that phosphorylation of PECAM-1 by Src or Csk family
      kinases was sufficient to trigger its association with SHP-2. Moreover, it was
      able to promote binding of PECAM-1 to SHP-1, a SHP-2-related protein-tyrosine
      phosphatase expressed in hemopoietic cells. Taken together, these findings
      indicated that the Src and Csk families of kinases are strong candidates for
      mediating tyrosine phosphorylation of PECAM-1 and triggering its association with
      SH2 domain-containing phosphatases under physiological circumstances.

PMID- 9624176
TI  - A membrane-proximal tyrosine-based signal mediates internalization of the HIV-1
      envelope glycoprotein via interaction with the AP-2 clathrin adaptor.
AB  - The envelope glycoprotein (Env) of human immunodeficiency virus, type 1 (HIV-1)
      undergoes rapid internalization after its transport to the cell surface. Env
      internalization is dependent upon information contained within the cytosolic
      domain of the protein. Here, we report that the cytosolic domain of Env binds
      specifically to the medium chain, mu 2, of the clathrin-associated protein
      complex AP-2, as well as to the complete AP-2 complex. The Env cytosolic domain
      contains two highly conserved tyrosine-based motifs (Y712SPL and Y768HRL), both
      of which are capable of binding to mu 2 when presented as short peptides.
      However, only the membrane-proximal motif Y712SPL binds to mu 2 and is required
      for internalization in the context of the whole cytosolic domain of Env. A
      glycine residue (Gly711) adjacent to the Y712SPL motif is also important for
      binding to mu 2/AP-2 and internalization. These observations suggest that the
      accessibility of the membrane-proximal GY712SPL to mu 2/AP-2 determines its
      function as a signal for recruitment of HIV-1 Env into clathrin-coated pits and
      its ensuing internalization.

PMID- 9624177
TI  - Phosphatidylinositol-4-phosphate 5-kinase localized on the plasma membrane is
      essential for yeast cell morphogenesis.
AB  - Phosphatidylinositol 4,5-biphosphate (PtdIns(4,5)P2), an important element in
      eukaryotic signal transduction, is synthesized either by phosphatidylinositol-4
      phosphate 5-kinase (PtdIns(4)P 5K) from phosphatidylinositol 4-phosphate
      (PtdIns(4)P) or by phosphatidylinositol-5-phosphate 4-kinase (PtdIns(5)P 4K) from
      phosphatidylinositol 5-phosphate (PtdIns(5)P). Two Saccharomyces cerevisiae
      genes, MSS4 and FAB1, are homologous to mammalian PtdIns(4)P 5Ks and PtdIns(5)P
      4Ks. We show here that MSS4 is a functional homolog of mammalian PtdIns(4)P 5K
      but not of PtdIns(5)P 4K in vivo. We constructed a hemagglutinin epitope-tagged
      form of Mss4p and found that Mss4p has PtdIns(4)P 5K activity. Immunofluorescent
      and fractionation studies of the epitope-tagged Mss4p suggest that Mss4p is
      localized on the plasma membrane, whereas Fab1p is reportedly localized on the
      vacuolar membrane. A temperature-sensitive mss4-1 mutant was isolated, and its
      phenotypes at restrictive temperatures were found to include increased cell size,
      round shape, random distribution of actin patches, and delocalized staining of
      cell wall chitin. Thus, biochemical and genetic analyses on Mss4p indicated that
      yeast PtdIns(4)P 5K localized on the plasma membrane is required for actin
      organization.

PMID- 9624178
TI  - MSS4, a phosphatidylinositol-4-phosphate 5-kinase required for organization of
      the actin cytoskeleton in Saccharomyces cerevisiae.
AB  - The Saccharomyces cerevisiae protein MSS4 is essential and homologous to
      mammalian phosphatidylinositol-4-phosphate (PI(4)P) 5-kinases. Here, we
      demonstrate that MSS4 is a lipid kinase. MSS4 has dual substrate specificity in
      vitro, converting PI(4)P to PI(4, 5)P2 and to a lesser extent PI(3)P to
      PI(3,4)P2; no activity was detected with PI or PI(5)P as a substrate. Cells
      overexpressing MSS4 contain an elevated level specifically of PI(4,5)P2, whereas
      mss4 mutant cells have only approximately 10% of the normal amount of this
      phosphorylated phosphoinositide. Furthermore, cells lacking MSS4 are unable to
      form actin cables and to properly localize their actin cytoskeleton during
      polarized cell growth. Overexpression of RHO2, encoding a Rho-type GTPase
      involved in regulation of the actin cytoskeleton, restores growth and polarized
      distribution of actin in an mss4 mutant. These results suggest that MSS4 is the
      major PI(4)P 5-kinase in yeast and provide a link between phosphoinositide
      metabolism and organization of the actin cytoskeleton in vivo.

PMID- 9624180
TI  - Gbeta gamma-independent coupling of alpha2-adrenergic receptor to p21(rhoA) in
      preadipocytes.
AB  - In preadipocytes, alpha2-adrenergic receptor (alpha2-AR) stimulation leads to a
      Gi/Go-dependent rearrangement of actin cytoskeleton. This is characterized by a
      rapid cell spreading, the formation of actin stress fibers, and the increase in
      tyrosyl phosphorylation of the focal adhesion kinase (pp125(FAK)). These cellular
      events being tightly controlled by the small GTPase p21(rhoA), the existence of a
      Gi/Go-dependent coupling of alpha2-AR to p21(rhoA) in preadipocytes was proposed.
      In alpha2AF2 preadipocytes (a cell clone derived from the 3T3F442A preadipose
      cell line and which stably expresses the human alpha2C10-adrenergic receptor)
      alpha2-adrenergic-dependent induction of cell spreading, formation of actin
      stress fibers, and increase in tyrosyl phosphorylation of pp125(FAK) were
      abolished by pretreatment of the preadipocytes with the C3 exoenzyme, a toxin
      which impairs p21(rhoA) activity by ADP-ribosylation. Conversely, C3 exoenzyme
      had no effect on the alpha2-adrenergic-dependent increase in tyrosyl
      phosphorylation and shift of ERK2 mitogen-activated protein kinase. alpha2
      Adrenergic stimulation also led to an increase in GDP/GTP exchange on p21(rhoA),
      as well as to an increase in the amount of p21(rhoA) in the particulate fraction
      of alpha2AF2 preadipocytes. Stable transfection of alpha2AF2 preadipocytes with
      the COOH-terminal domain of betaARK1 (betaARK-CT) (a blocker of Gbeta gamma
      action), strongly inhibited the alpha2-adrenergic-dependent increase in tyrosyl
      phos- phorylation and shift of ERK2, without modification of the tyrosyl
      phosphorylation of pp125(FAK) and spreading of preadipocytes. These results show
      that alpha2-adrenergic-dependent reorganization of actin cytoskeleton requires
      the activation of p21(rhoA) in preadipocytes. Conversely to the activation of the
      p21(ras)/mitogen-activated protein kinase pathway, the alpha2-adrenergic
      activation of p21(rhoA)-dependent pathways are independent of the beta gamma
      subunits of heterotrimeric G proteins.

PMID- 9624179
TI  - Ultraviolet radiation triggers the ribotoxic stress response in mammalian cells.
AB  - The ribotoxic stress response, which is conserved between prokaryotes and
      eukaryotes, is a cellular reaction to cytotoxic interference with the function of
      the 3'-end of the large (23 S/28 S) ribosomal RNA. The 3'-end of the large rRNA
      is directly involved in the three sequential steps of translational elongation:
      the aminoacyl-tRNA binding, the peptidyl transfer, and the ribosomal
      translocation. In mammalian cells, the ribotoxic stress response involves
      activation of the stress-activated protein kinase/c-Jun NH2-terminal kinase and
      the p38 mitogen-activated protein kinase and transcriptional induction of
      immediate early genes such as c-fos and c-jun. Active ribosomes are essential
      mediators of the ribotoxic stress response. We demonstrate here that the
      transcriptional response of mammalian cells to ultraviolet radiation (UV
      response) displays the characteristics of a ribotoxic stress response, inasmuch
      as (i) the activation of stress kinases and gene expression in response to UV
      requires the presence of active ribosomes at the moment of irradiation; (ii) UV
      irradiation inhibits protein synthesis; and (iii) irradiation of cells with UV
      causes specific damage to the 3'-end of the 28 S rRNA. In contrast, the
      activation of the stress kinases by hyperosmolarity, by the DNA-cross-linking
      agent diepoxybutane, or by growth factors and cytokines does not depend on the
      presence of active ribosomes. Our results identify UV as a potential ribotoxic
      stressor and support the notion that some of the cellular signaling cascades in
      response to UV might be generated in the ribosome, possibly triggered by damage
      to rRNA.

PMID- 9624181
TI  - A functional fibroblast growth factor-1 immunoglobulin fusion protein.
AB  - Proteins of the fibroblast growth factor (FGF) family play diverse roles in
      embryonic development, angiogenesis, and wound healing. The most well studied
      targets of FGF activity typically are cells of mesodermal and neuroectodermal
      origin; in addition, expression of FGF-1 (acidic FGF) is increased at several
      sites of chronic immunologic injury, and recent studies show that FGF-1 also may
      interact with cells of the immune system. In some human T cells, FGF-1 can induce
      signals necessary for production of interleukin-2, a key cytokine required for T
      cell proliferation. To better characterize the interaction of FGF-1 with FGF
      receptors on T cells, a fusion protein was constructed containing a portion of
      the constant region of human IgG1 (Fc) at the amino terminus of FGF-1. The Fc-FGF
      1 fusion protein retained FGF function as determined by stimulation of tyrosine
      phosphorylation and DNA synthesis in NIH 3T3 cells. Binding of the intact fusion
      protein to FGF receptor 1 (FGFR1) on T cells was demonstrated by
      immunoprecipitation of the receptor bound to Fc-FGF-1 and by flow cytometry
      showing binding of fusion protein to T cells expressing FGFR1. This functional Fc
      FGF-1 protein should prove useful in identifying FGFR-expressing cells.

PMID- 9624182
TI  - The vesicle transport protein Vps33p is an ATP-binding protein that localizes to
      the cytosol in an energy-dependent manner.
AB  - Molecular mechanisms of vesicle transport between the prevacuolar compartment and
      the vacuole in yeast or the lysosome in mammalian cells are poorly understood. To
      learn more about the specificity of this intercompartmental step, we have
      examined the subcellular localization of a SEC1 homologue, Vps33p, a protein
      implicated to function in transport between the prevacuolar compartment and the
      vacuole. Following short pulses, 80-90% of newly synthesized Vps33p
      cofractionated with a cytosolic enzyme marker after making permeabilized yeast
      cells. However, during a chase, 20-40% of Vps33p fractionated with permeabilized
      cell membranes in a time-dependent fashion with a half-time of approximately 40
      min. Depletion of cellular ATP increased the association rate to a half-time of
      approximately 4 min and caused 80-90% of newly synthesized Vps33p to be
      associated with permeabilized cell membranes. The association of Vps33p with
      permeabilized cell membranes was reversible after restoring cells with glucose
      before permeabilization. The N-ethylmaleimide-sensitive fusion protein homologue,
      Sec18p, a protein with known ATP binding and hydrolysis activity, displayed the
      same reversible energy-dependent sedimentation characteristics as Vps33p. We
      determined that the photosensitive analog, 8-azido-[alpha-32P]ATP, could bind
      directly to Vps33p with low affinity. Interestingly, excess unlabeled ATP could
      enhance photoaffinity labeling of 8-azido-[alpha-32P]ATP to Vps33p, suggesting
      cooperative binding, which was not observed with excess GTP. Importantly, we did
      not detect significant photolabeling after deleting amino acid regions in Vps33p
      that show similarity to ATP interaction motifs. We visualized these events in
      living yeast cells after fusing the jellyfish green fluorescent protein (GFP) to
      the C terminus of full-length Vps33p. In metabolically active cells, the fully
      functional Vps33p-GFP fusion protein appeared to stain throughout the cytoplasm
      with one or two very bright fluorescent spots near the vacuole. After depleting
      cellular ATP, Vps33p-GFP appeared to localize with a punctate morphology, which
      was also reversible upon restoring cells with glucose. Overall, these data
      support a model where Vps33p cycles between soluble and particulate forms in an
      ATP-dependent manner, which may facilitate the specificity of transport vesicle
      docking or targeting to the yeast lysosome/vacuole.

PMID- 9624183
TI  - A cytoplasmic acyl-protein thioesterase that removes palmitate from G protein
      alpha subunits and p21(RAS).
AB  - Thioacylation is one of a handful of reversible covalent protein modifications,
      but the enzymes responsible for addition and removal of long chain fatty acids
      from protein cysteine residues in vivo have not yet been identified. The alpha
      subunits of some heterotrimeric G proteins cycle between thioacylated and
      deacylated states in a receptor-regulated fashion. We have identified, purified,
      and characterized an enzyme acyl-protein thioesterase that deacylates Galpha
      proteins and at least some other thioacyl protein substrates, including Ha-RAS.
      The action of this enzyme on thioacylated heterotrimeric Gs is regulated by
      activation of the G protein. Although native and recombinant acyl-protein
      thioesterases act as both acyl-protein thioesterases and lysophospholipases in
      vitro, we demonstrate by transfection that the enzyme can accelerate the turnover
      of thioacyl groups on Gsalpha in vivo.

PMID- 9624184
TI  - Role of carbohydrate-mediated adherence in cytopathogenic mechanisms of
      Acanthamoeba.
AB  - Acanthamoeba keratitis is a vision-threatening corneal infection. The mannose
      binding protein of Acanthamoeba is thought to mediate adhesion of parasites to
      host cells. We characterized the amoeba lectin with respect to its carbohydrate
      binding properties and the role in amoeba-induced cytopathic effect (CPE). Sugar
      inhibition assays revealed that the amoeba lectin has the highest affinity for
      alpha-Man and Man(alpha1-3)Man units. In vitro cytopathic assays indicated that
      mannose-based saccharides which inhibit amoeba adhesion to corneal epithelial
      cells were also potent inhibitors of amoeba-induced CPE. Another major finding
      was that N-acetyl-D-glucosamine (GlcNAc) which does not inhibit adhesion of
      amoeba to host cells is also an inhibitor of amoeba-induced CPE. The
      Acanthamoebae are thought to produce CPE by secreting cytotoxic proteinases. By
      zymography, one metalloproteinase and three serine proteinases were detected in
      the conditioned media obtained after incubating amoebae with the host cells. The
      addition of free alpha-Man and GlcNAc to the co-culture media inhibited the
      secretion of the metalloproteinase and serine proteinases, respectively. In
      summary, we have shown that the lectin-mediated adhesion of the Acanthamoeba to
      host cells is a prerequisite for the amoeba-induced cytolysis of target cells and
      have implicated a contact-dependent metalloproteinase in the cytopathogenic
      mechanisms of Acanthamoeba.

PMID- 9624185
TI  - Disruption of redox homeostasis in the transforming growth factor-alpha/c-myc
      transgenic mouse model of accelerated hepatocarcinogenesis.
AB  - In previous studies we have demonstrated that transforming growth factor (TGF)
      alpha/c-myc double transgenic mice exhibit an enhanced rate of cell
      proliferation, accumulate extensive DNA damage, and develop multiple liver tumors
      between 4 and 8 months of age. To clarify the biochemical events that may be
      responsible for the genotoxic and carcinogenic effects observed in this
      transgenic model, several parameters of redox homeostasis in the liver were
      examined prior to development of hepatic tumors. By 2 months of age, production
      of reactive oxygen species, determined by the peroxidation-sensitive fluorescent
      dye, 2',7'-dichlorofluorescin diacetate, was significantly elevated in TGF
      alpha/c-myc transgenic hepatocytes versus either wild type or c-myc single
      transgenic cells, and occurred in parallel with an increase in lipid
      peroxidation. Concomitantly with a rise in oxidant levels, antioxidant defenses
      were decreased, including total glutathione content and the activity of
      glutathione peroxidase, whereas thioredoxin reductase activity was not changed.
      However, hepatic tumors which developed in TGF-alpha/c-myc mice exhibited an
      increase in thioredoxin reductase activity and a very low activity of glutathione
      peroxidase. Furthermore, specific deletions were detected in mtDNA as early as 5
      weeks of age in the transgenic mice. These data provide experimental evidence
      that co-expression of TGF-alpha and c-myc transgenes in mouse liver promotes
      overproduction of reactive oxygen species and thus creates an oxidative stress
      environment. This phenomenon may account for the massive DNA damage and
      acceleration of hepatocarcinogenesis observed in the TGF-alpha/c-myc mouse model.

PMID- 9624186
TI  - Isolation and characterization of laminin-10/11 secreted by human lung carcinoma
      cells. laminin-10/11 mediates cell adhesion through integrin alpha3 beta1.
AB  - A panel of human tumor cell lines was screened for selective expression of
      laminin alpha5 chain, a newly identified laminin subunit comprising laminin-10
      (alpha5 beta1 gamma1) and -11 (alpha5 beta2 gamma1). The lung adenocarcinoma cell
      line A549 was found to express the alpha5 chain at relatively high levels but no
      detectable amounts of other alpha chains. The laminin variants containing alpha5
      chain were purified from the conditioned medium of A549 cells by immunoaffinity
      chromatography using the anti-laminin monoclonal antibody 4C7 which was shown
      recently to recognize the laminin alpha5 chain (Tiger, C.-F., Champliaud, M.-F.,
      Pedrosa-Domellof, F., Thornell, L.-E., Ekblom, P., and Gullberg, D. (1997) J.
      Biol. Chem. 272, 28590-28595). The purified laminin variants consisted of three
      chains with molecular masses of 350, 220, and 210 kDa. The 350-kDa chain was
      specifically recognized by another anti-alpha5 chain monoclonal antibody capable
      of recognizing denatured alpha5 chain on immunoblots, whereas the 210-kDa chain
      was recognized by an anti-gamma1 chain antibody. The purified alpha5 chain
      containing laminin variants (hereafter referred to as laminin-10/11) were highly
      active in mediating adhesion of A549 cells to the substratum with potency as high
      as that of laminin-5 and significantly higher than those of laminin-1, laminin
      2/4, or fibronectin. Adhesion to substrata coated with laminin-10/11 was
      specifically inhibited by anti-integrin antibodies directed against the integrin
      alpha3 or beta1 subunit but not by those against alpha2 or alpha6 subunit,
      indicating that laminin-10/11 is specifically recognized by integrin alpha3
      beta1. Given the wide distribution of laminin-10/11 in the basement membrane of
      various tissue types and dominant expression of integrin alpha3 beta1 in most
      epithelial cells, specific interaction of laminin-10/11 with integrin alpha3
      beta1 may play an important role in in vivo regulation of proliferation and
      differentiation of epithelial cells through the basement membrane.

PMID- 9624187
TI  - Biochemical properties of two protein kinases involved in disease resistance
      signaling in tomato.
AB  - In tomato plants, resistance to bacterial speck disease is mediated by a
      phosphorylation cascade, which is triggered by the specific recognition between
      the plant serine/threonine protein kinase Pto and the bacterial AvrPto protein.
      In the present study, we investigated in vitro biochemical properties of Pto,
      which appears to function as an intracellular receptor for the AvrPto signal
      molecule. Pto and its downstream effector Pti1, which is also a serine/threonine
      protein kinase, were expressed in Escherichia coli as maltose-binding protein and
      glutathione S-transferase fusion proteins, respectively. The two kinases each
      autophosphorylated at multiple sites as determined by phosphopeptide mapping. In
      addition, Pto and Pti1 autophosphorylation occurred via an intramolecular
      mechanism, as their specific activity was not affected by their molar
      concentration in the assay. Moreover, an active glutathione S-transferase-Pto
      fusion failed to phosphorylate an inactive maltose-binding protein-Pto(K69Q)
      fusion excluding an intermolecular mechanism of phosphorylation for Pto. Pti1
      phosphorylation by Pto was also characterized and found to occur with a Km of 4.1
      microM at sites similar to those autophosphorylated by Pti1. Pto and the product
      of the recessive allele pto phosphorylated Pti1 at similar sites, as observed by
      phosphopeptide mapping. This suggests that the inability of the kinase pto to
      confer resistance to bacterial speck disease in tomato is not caused by altered
      recognition specificity for Pti1 phosphorylation sites.

PMID- 9624188
TI  - The molecular basis for the absence of N-glycolylneuraminic acid in humans.
AB  - N-Glycolylneuraminic acid (NeuGc) is abundantly expressed in most mammals, but it
      is not detectable in humans. The expression of NeuGc is controlled by cytidine
      monophospho-N-acetylneuraminic acid (CMP-NeuAc) hydroxylase activity. We
      previously cloned a cDNA for mouse CMP-NeuAc hydroxylase and found that the human
      genome contains a homologue. We report here the molecular basis for the absence
      of NeuGc in humans. We cloned a cDNA for human CMP-NeuAc hydroxylase from a HeLa
      cell cDNA library. The cDNA encodes a 486-amino acid protein, and its deduced
      amino acid sequence lacks a domain corresponding to the N-terminal 104 amino
      acids of the mouse CMP-NeuAc hydroxylase protein, although the human protein is
      highly identical (93%) to the rest of the mouse hydroxylase protein. The N
      terminal truncation of the human hydroxylase is caused by deletion of a 92-base
      pair-long exon in human genomic DNA. The human hydroxylase expressed in COS-7
      cells exhibited no enzymatic activity, and a mouse hydroxylase mutant, which
      lacks the N-terminal domain, was also inactive. A chimera composed of the human
      hydroxylase and the N-terminal domain of the mouse hydroxylase displayed the
      enzyme activity. These results indicate that the human homologue of CMP-NeuAc
      hydroxylase is inactive because it lacks an N-terminal domain that is essential
      for enzyme activity. The absence of NeuGc in human glycoconjugates is due to a
      partial deletion in the gene that encodes CMP-NeuAc hydroxylase.

PMID- 9624189
TI  - Phospholipid- and GTP-dependent activation of cholera toxin and phospholipase D
      by human ADP-ribosylation factor-like protein 1 (HARL1).
AB  - ADP-ribosylation factors (ARFs), 20-kDa guanine nucleotide-binding proteins named
      for their ability to activate cholera toxin (CT) ADP-ribosyltransferase activity,
      have a critical role in vesicular transport and activate a phospholipase D (PLD)
      isoform. Although ARF-like (ARL) proteins are very similar in sequence to ARFs,
      they were initially believed not to activate CT or PLD. mRNA for human ARL1
      (hARL1), which is 57% identical in amino acid sequence to hARF1, is present in
      all tissues, with the highest amounts in kidney and pancreas and barely
      detectable amounts in brain. Relative amounts of hARL1 protein were similar to
      mRNA levels. Purified hARL1 (rARL1) synthesized in Escherichia coli had less
      activity toward PLD than did rARF1, although PLD activation by both proteins was
      guanosine guanosine 5'-(gamma-thio)triphosphate (GTPgammaS)-dependent. ARL1
      stimulation of CT-catalyzed ADP-ribosylation was considerably less than that by
      rARF1 and was phospholipid dependent. GTPgammaS-binding by rARL1 was also
      phospholipid- and detergent-dependent, and in assays containing
      phosphatidylserine, was greater than that by rARF1. In vitro, the activities of
      rARL1 and rARF1 are similar. Rather than being a member of a separate subfamily,
      hARL1, which activates PLD and CT in a phospholipiddependent manner, appears to
      be part of a continuum of ARF family proteins.

PMID- 9624190
TI  - Prolongation of the QT interval and the sudden infant death syndrome.
AB  - BACKGROUND: The sudden infant death syndrome (SIDS) is multifactorial in origin,
      but its causes remain unknown. We previously proposed that prolongation of the QT
      interval on the electrocardiogram, possibly resulting from a developmental
      abnormality in cardiac sympathetic innervation, may increase the risk of life
      threatening ventricular arrhythmias and contribute to this devastating disorder.
      We prospectively tested this hypothesis. METHODS: Between 1976 and 1994, we
      recorded electrocardiograms on the third or fourth day of life in 34,442 newborns
      and followed them prospectively for one year. The QT interval was analyzed with
      and without correction for the heart rate. RESULTS: One-year follow-up data were
      available for 33,034 of the infants. There were 34 deaths, of which 24 were due
      to SIDS. The infants who died of SIDS had a longer corrected QT interval (QTc)
      than did the survivors (mean [+/-SD], 435+/-45 vs. 400+/-20 msec, P<0.01) and the
      infants who died from causes other than SIDS (393+/-24 msec, P<0.05). Moreover,
      12 of the 24 SIDS victims but none of the other infants had a prolonged QTc
      (defined as a QTc greater than 440 msec). When the absolute QT interval was
      determined for similar cardiac-cycle lengths, it was found that 12 of the 24
      infants who died of SIDS had a QT value exceeding the 97.5th percentile for the
      study group as a whole. The odds ratio for SIDS in infants with a prolonged QTc
      was 41.3 (95 percent confidence interval, 17.3 to 98.4). CONCLUSIONS:
      Prolongation of the QT interval in the first week of life is strongly associated
      with SIDS. Neonatal electrocardiographic screening may permit the early
      identification of a substantial percentage of infants at risk for SIDS, and the
      institution of preventive measures may therefore be possible.

PMID- 9624191
TI  - Long-term prognosis of seizures with onset in childhood.
AB  - BACKGROUND: The long-term prognosis of seizures that begin in childhood is
      uncertain. METHODS: We prospectively studied 245 children from the catchment area
      of Turku University Hospital in Turku, Finland, who had active epilepsy diagnosed
      between 1961 and 1964. Sixty-eight patients (28 percent) had idiopathic seizures
      (presumed to have a genetic origin), 54 (22 percent) had cryptogenic seizures
      (occurring in otherwise normal persons with no clear cause), and 123 (50 percent)
      had remote symptomatic seizures (with no immediate cause but occurring in persons
      with a prior brain injury or a static encephalopathy). RESULTS: At the final
      follow-up in 1992, we had sufficient data on 220 patients (90 percent), 176 of
      whom were alive and 44 of whom had died; the remaining 25 had emigrated, could
      not be traced, or declined to participate. Thirty-nine patients who died were not
      free of seizures at the time of death, and 33 had remote symptomatic seizures.
      Among the surviving patients, 112 (64 percent) had been seizure-free for at least
      five years, including 83 (47 percent) who were not taking antiepileptic
      medications. The most important predictors of being seizure-free for at least
      five years were a rapid response to therapy (defined as a reduction in the
      frequency of seizures of 75 to 100 percent within three months of beginning
      treatment) and a diagnosis of idiopathic seizures. As compared with a matched
      control group, 99 patients with epilepsy but no other initial neurologic
      impairment were of similar socioeconomic status and had similar rates of passing
      an examination given after 12 years of school. Significantly more patients,
      however, had completed only six years of school (relative risk, 2.13), were
      unemployed (relative risk, 3.76), were not married (relative risk, 3.50), and did
      not have children (relative risk, 3.00). CONCLUSIONS: Although the majority of
      patients with epilepsy in childhood are free of seizures by the time they become
      adults, they are at increased risk for social and educational problems. Patients
      whose epilepsy does not remit also have an increased risk of death.

PMID- 9624192
TI  - Long-term intellectual and behavioral outcomes of children with febrile
      convulsions.
AB  - BACKGROUND: Hospital-based studies have reported that children with febrile
      convulsions have subsequent mental retardation and behavior problems. In
      contrast, population-based studies have reported a better outcome. METHODS: We
      identified 398 children with febrile convulsions among 14,676 children enrolled
      in the Child Health and Education Study, a national population-based study in the
      United Kingdom of children born in one week in April 1970. The children were
      comprehensively assessed at the age of 10. After excluding 16 children who had
      neurodevelopmental problems before their first febrile convulsion and 1 child
      whose case was atypical, we studied 381 children, 287 with simple febrile
      convulsions and 94 with complex febrile convulsions. We compared them with the
      rest of the cohort using measures of academic progress, intelligence, and
      behavior that included questionnaires, standardized tests, and formal tests.
      RESULTS: At the 10-year assessment, only 4 of 102 measures of academic progress,
      intelligence, and behavior differed significantly between the entire group of
      children with febrile convulsions and the group without febrile convulsions -- no
      more than would be expected by chance. Similar results were found when children
      with simple febrile convulsions and those with complex febrile convulsions were
      analyzed separately. The children with recurrent episodes of febrile convulsions
      had outcomes similar to those of the children with only one episode each. Special
      schooling was required for more children who had febrile convulsions in the first
      year of life than for those who had had them later in life (5 of 67, or 7.5
      percent, vs. 4 of 265, or 1.5 percent; P=0.02), but these numbers were small.
      CONCLUSION: Children who had febrile convulsions performed as well as other
      children in terms of their academic progress, intellect, and behavior at 10 years
      of age.

PMID- 9624193
TI  - Male hypogonadism due to a mutation in the gene for the beta-subunit of follicle
      stimulating hormone.

PMID- 9624194
TI  - Hospitalization costs associated with homelessness in New York City.
AB  - BACKGROUND: Homelessness is believed to be a cause of health problems and high
      medical costs, but data supporting this association have been difficult to
      obtain. We compared lengths of stay and reasons for hospital admission among
      homeless and other low-income persons in New York City to estimate the
      hospitalization costs associated with homelessness. METHODS: We obtained hospital
      discharge data on 18,864 admissions of homeless adults to New York City's public
      general hospitals (excluding admissions for childbirth) and 383,986 nonmaternity
      admissions of other low-income adults to all general hospitals in New York City
      during 1992 and 1993. The differences in length of stay were adjusted for
      diagnosis-related group, principal diagnosis, selected coexisting illnesses, and
      demographic characteristics. RESULTS: Of the admissions of homeless people, 51.5
      percent were for treatment of substance abuse or mental illness, as compared with
      22.8 percent for the other low-income patients, and another 19.7 percent of the
      admissions of homeless people were for trauma, respiratory disorders, skin
      disorders, and infectious diseases (excluding the acquired immunodeficiency
      syndrome [AIDS]), many of which are potentially preventable medical conditions.
      For the homeless, 80.6 percent of the admissions involved either a principal or a
      secondary diagnosis of substance abuse or mental illness -- roughly twice the
      rates for the other patients. The homeless patients stayed 4.1 days, or 36
      percent, longer per admission on average than the other patients, even after
      adjustments were made for differences in the rates of substance abuse and mental
      illness and other clinical and demographic characteristics. The costs of the
      additional days per discharge averaged $4,094 for psychiatric patients, $3,370
      for patients with AIDS, and $2,414 for all types of patients. CONCLUSIONS:
      Homelessness is associated with substantial excess costs per hospital stay in New
      York City. Decisions to fund housing and supportive services for the homeless
      should take into account the potential of these services to reduce the high costs
      of hospitalization in this population.

PMID- 9624195
TI  - Infection in organ-transplant recipients.

PMID- 9624197
TI  - Prolongation of the QT interval and the sudden infant death syndrome.

PMID- 9624198
TI  - The homeless and the public household.

PMID- 9624200
TI  - Nursing and the procurement of organs and tissues in the acute care hospital
      setting.
AB  - Organ and tissue transplantations are now well established procedures; however, a
      scarcity of donors and the obstacles encountered during the procurement process
      have resulted in a growing shortage of organs and tissues. This paper reviews the
      issues surrounding the procurement process and the role that nurses play in that
      process. Two case studies are presented and discussed in order to identify
      important issues to address with the family (i. e., clarification about the
      meaning of brain death, the impact of donation on funeral arrangements, and the
      costs of donation) and to suggest practical strategies for approaching these
      issues.

PMID- 9624201
TI  - Ethical implications of caring in rehabilitation.
AB  - The establishment of special caring relationships between spinal cord injured
      individuals (SCI) and nurses or therapists during rehabilitation creates unique
      ethical dilemmas. This paper will explore the practical and ethical implications
      for health care professionals who feel a moral imperative, compelled by their
      special relationship with a particular SCI individual, to "break the rules"
      within a rehabilitation bureaucracy in order to provide individualized health
      care. From the staff perspective two issues will be examined: the status of
      special relationships in a health care organization and the ability to maintain
      one's personal and professional standards in a managed care environment. From the
      administrative perspective two ethical issues will be explored: the challenge of
      pursuing the good of the patient and the organization while navigating between
      the public and private spheres of health care in a health care system that values
      standardization.

PMID- 9624202
TI  - Issues for nurses regarding elder autonomy.
AB  - This article reviews issues related to elder autonomy that challenge nurses in
      their daily practice. Maintaining and promoting quality patient care is paramount
      to the profession of nursing. Included in that promotion is the need for nurses
      to remain sensitive to the older individual's desire to act autonomously and make
      life choices. A brief review of limitations to elder autonomy is included, as
      well as examples of research studying autonomous action on the part of the
      elderly. The completing ethical principle of beneficence is briefly discussed and
      the issue of competency is considered. Autonomy remains a concern for all health
      care providers, in particular, the role of the nurse is to support the decision
      making of the older adult and provide needed information to allow the elderly
      person to make decisions based on what is right for him or her.

PMID- 9624203
TI  - Ethical implications of genetic testing.
AB  - Advances in biotechnology have created previously unforeseen possibilities to
      determine the genetic make-up of individuals and to predict the health of future
      societies. This article identifies some of the issues and dilemmas confronted by
      health professionals and consumers as these technologic advances move from the
      laboratory to the clinical setting.

PMID- 9624204
TI  - Neonatal intensive care: decision making in the face of prognostic uncertainty.
AB  - This article discusses ethical decisions faced by parents and physicians in
      evaluating neonates. The role of the neonatal nurse is to be caretaker of the
      most vulnerable. The nurse assumes the role of safeguarding the infant's well
      being, necessitating both parental engagement and work within an
      interdisciplinary team.

PMID- 9624205
TI  - Enhancing nurses' ethical practice: development of a clinical ethics program.
AB  - There is increasing attention paid to ethics under managed care; however, few
      clinical-based ethics programs are reported. This paper reports the assessment
      and outcomes of one such program. A quasi-experimental research design with t
      tests is used to assess the outcome differences between participants and control
      groups. There are twenty nurses in each; they are assessed for comparability.
      Differences are predicted on two outcomes using reliable and valid measures:
      nurses' time with their patients in ethics discussions, and nurses' opinions
      regarding their clinical ethics environments. Results reveal a statistically
      significant difference (p <.05) between the two groups, with modest positive
      change in the participants. Additional exploratory analyses are reported on
      variables influential in health care services.

PMID- 9624206
TI  - Ethical working relationships in patient care: challenges and possibilities.
AB  - This article traces the historical concern for building and maintaining effective
      working relationships between nurses and physicians on behalf of patients. The
      author takes the position that compassionate patient care requires collegial and
      collaborative working relationships both within nursing and between nursing and
      medicine. The development and support of such relationships is obligatory on the
      part of nursing, medicine, and administration. Selected studies and expert
      opinion are used to support this position. Practical and visionary models that
      guide interprofessional relationships are discussed with a goal of creating
      organizational structures which are supportive of ethical practice and benefit
      patients and caregivers.

PMID- 9624207
TI  - Ethical dimensions of nurse-physician relations in critical care.
AB  - Recent research findings highlight the importance of nurse-physician
      collaboration for more positive patient outcomes. Nowhere is this more important
      than in addressing the ethical aspects of critical care practice. Differences in
      values, communication, trust, and responsibilities can precipitate conflict
      between nurses and physicians over ethical components of care. Strategies to
      address these ethical conflicts and improve nurse-physician collaboration are
      needed at both the organization and policy level.

PMID- 9624208
TI  - Defining futility in neonatal intensive care.
AB  - This article presents an initial conceptualization of futility in neonatal
      intensive care in an attempt to stimulate thoughtful debate an further
      development of the concept. Futility is defined within the context of the
      infant's response to a trial of therapy for extreme prematurity. Substantial
      criteria for determining whether futility has been reached focus on whether the
      infant has sustained physiologic complications that have been shown in follow-up
      studies to be related to mortality and significant morbidity.

PMID- 9624209
TI  - Multicultural issues and ethical concerns in the delivery of nursing care
      interventions.
AB  - Nurses are beginning to recognize the importance of understanding the values,
      beliefs, and health practices of different cultures in order to provide care that
      is appropriate and culturally relevant to diverse patient populations.
      Individuals from other cultures may have different languages and customs. These
      cultural factors are important to the nurse's understanding of the specifics of
      health care practice. Culture and ethnicity may influence one's physical
      development and exposure to health compromising environments and conditions. This
      article uses a case study to describe a process that health care providers can
      use when faced with ethical dilemmas that arise when caring for patients from
      different cultures. Nursing strategies to promote culturally sensitive care are
      discussed, and include cultural assessment, heightening sensitivity to ethical
      issues in cultural diversity, and the role of continuing education in providing
      culturally competent care.

PMID- 9624210
TI  - Ethical environment: reports of practicing nurses.
AB  - Reports from the development of the Ethics Environment Questionnaire identify
      three critical features for ethical environments in health care settings of
      registered nurses. They are the ability of nurses to engage in discussions about
      patient care, support from administrators, and the development of policies
      procedures that support their practice. Implications for clinical practicing
      nurses are explored.

PMID- 9624211
TI  - The future of ethical decision making in health care.
AB  - As health care has become more complex in light of technological, economic, and
      organizational advances and changes, ethics has increasingly become a required
      component in decision making. This article examines four major trends:
      philosophical and practical problems with the place of ethics in health care, the
      necessity to broaden the focus of ethics committees, increase emphasis on
      interprofessional collaboration, and changes in the marketplace of health care
      delivery that will impact ethical decision making in the future.

PMID- 9624212
TI  - Cancer gene therapy.
AB  - Developments in molecular genetics, immunology, molecular and cellular biology,
      and tumor biology have given rise to the field of cancer gene therapy. Several
      gene delivery vehicles have been developed and are being examined in clinical
      trials. Most cancer gene therapy strategies involve introduction of genes to
      augment existing therapies. An overview is provided on gene delivery vehicles,
      gene therapy strategies, and cancer gene therapy clinical trials.

PMID- 9624213
TI  - Genetically modified tumor cell vaccines.
AB  - Recent progress in identifying tumor antigens and understanding the host-tumor
      relationship have catalyzed a dramatic expansion of efforts to develop cancer
      vaccines. Gene transfer technologies have figured prominently in the design of
      many of these novel immunization schemes. This article highlights some of the key
      principles and controversies raised by experiments involving genetically modified
      tumor vaccines and speculates about future directions for investigators in this
      field.

PMID- 9624214
TI  - Genetic approaches to adoptive cellular immunotherapy.
AB  - The ability to modify cells to express foreign genes has provided new venues in
      the treatment of cancer. These techniques have enabled investigators to generate
      more potent immune effector cells capable of mediating regression of established
      tumors. Some of these techniques are currently being evaluated in clinical
      trials.

PMID- 9624215
TI  - Cancer chemotherapy using suicide genes.
AB  - Suicide gene therapy is a unique form of drug delivery system that allows for
      negative selection of malignant cells using a prodrug approach. Malignant cells
      are transduced with a gene encoding an enzyme that can metabolize an otherwise
      nontoxic prodrug into a toxic metabolite. The prototype of this system is the
      herpes simplex virus thymidine kinase gene (HSV-tk). Suicide genes may be
      introduced into tumor cells either by viral vectors or nonviral methods. Current
      work is underway to fine tune both the delivery systems and optimize the efficacy
      of the production of the toxic metabolites. Suicide gene therapy is an exciting
      strategy currently in clinical trial in the treatment of a number of tumors.

PMID- 9624216
TI  - Cytokine gene therapy for human tumors.
AB  - Cytokine gene therapy is a potentially powerful antineoplastic strategy. It
      provides paracrine cytokine secretion in the region of putative tumor antigen
      that maximizes antitumor immune responses and minimizes systemic toxicity. A
      wealth of animal experimentation has demonstrated the effectiveness of cytokine
      gene therapy in a variety of tumor models. Enough evidence has mounted such that
      human cytokine gene therapy trials are underway throughout the United States and
      elsewhere.

PMID- 9624217
TI  - Transcriptional targeting for cancer gene therapy.
AB  - Novel treatment strategies incorporating gene transfer technology represent a new
      frontier in the treatment of cancer made possible through recent developments in
      molecular biology. Targeting of gene therapy strategies that rely on in situ gene
      modifications can theoretically occur at the gene entry or gene expression level.
      Regulation of gene transcription is made possible through the incorporation of
      cell-specific promoter and enhancer sequences within the transgene construct.
      This article provides a brief review of transcriptional processes and a
      description of the most widely studied cell-specific regulatory elements.

PMID- 9624218
TI  - Vaccinia virus for human gene therapy.
AB  - Recombinant vaccinia virus may be an ideal viral vector for cancer gene therapy.
      It has a large genome that is able to be engineered for the insertion and
      simultaneous expression of multiple genes. It reliably infects a large variety of
      tumors and expresses high levels of the gene(s) of interest. Although naturally
      cytopathic, it can be engineered to be noncytopathic but still infectious.
      Recently, it has been used in preclinical trials of animals and patients with
      cancer.

PMID- 9624219
TI  - Gene therapy for tumors of the central nervous system.
AB  - Primary central nervous system tumors, consisting mainly of malignant gliomas,
      represent a unique system for the study of gene transfer techniques. Exogenous
      transgenes have been delivered using retroviral, adenoviral, and herpes simplex
      virus vectors. A number of strategies have been developed, including: (1)
      delivery of prodrug activating genes, (2) replacement of tumor suppressor genes,
      (3) cytokine-mediated enhancement of antitumor immune responses, and (4)
      antisense cDNA delivery to block the action of growth factors, cell cycle
      proteins, and drug resistance mechanisms. Efforts to disrupt the blood brain
      barrier may facilitate tumor gene delivery.

PMID- 9624220
TI  - Gene therapy for human lung cancers.
AB  - Gene therapy, in the future, may offer new strategies to treat various
      malignancies in lung cancer. Several phase I trials have demonstrated the safety
      of these approaches. The limitation of current gene transfer techniques include
      transient gene expression, locoregional delivery, and the ability to target tumor
      tissue in a safe manner.

PMID- 9624221
TI  - Gene therapy for liver tumors.
AB  - The liver is a common site of metastases from solid tumors and the primary site
      for a number of malignancies. Cure rates for primary and metastatic liver tumors
      are low. Gene therapy is a novel approach to liver cancer that seeks to exploit
      differences between tumor cells and hepatocytes to achieve tumor eradication with
      preservation of normal hepatic parenchyma. Numerous strategies for tumor specific
      cytolysis are reviewed.

PMID- 9624222
TI  - Inadequate vitamin D status: does it contribute to the disorders comprising
      syndrome 'X'?
AB  - Environmental factors are important in the aetiology of glucose intolerance, type
      II diabetes and IHD. The lack of vitamin D, which is necessary for adequate
      insulin secretion, relates demographically to increased risk of myocardial
      infarction. These disorders are connected, degenerative vascular disease
      increasing with glucose intolerance and diabetes and, with its risk factors,
      comprising syndrome 'X'. Evidence is presented suggesting that vitamin D
      deficiency may be an avoidable risk factor for syndrome 'X', adding another
      preventative measure to current recommendations which are aimed at reducing the
      worldwide epidemic of these disorders. Experimentally, vitamin D deficiency
      progressively reduces insulin secretion; glucose intolerance follows and becomes
      irreversible. Relationships between vitamin D status, glucose tolerance and 30
      min insulin secretion during oral glucose tolerance tests are reported in British
      Asians; insulin secretion, but not glycaemia, improving with short-term
      supplementation. Studies showing reduction in blood pressure and in risk of heart
      attack and diabetes with exercise (usually outdoor), rarely consider the role of
      vitamin D status. Glycaemia and insulin secretion in elderly European men,
      however, relate to vitamin D status, independent of season or physical activity.
      Prolonged supplementation can improve glycaemia. Hypertension improves with
      vitamin D treatment with or without initial deficiency. Vitamin D status and
      climate are reviewed as risk factors for myocardial infarction; the risk reducing
      with altitude despite increasing cold. Glycaemia and fibrinogenaemia improve with
      insulin secretion increases in summer. Variation in vitamin D requirements could
      arise from genetic differences in vitamin D processing since bone density can
      vary with vitamin D-receptor genotype. Vitamin D receptors are present in islet
      beta cells and we report insulin secretion in healthy Asians differing profoundly
      with the Apa I genotype, being independent of vitamin D status. Those at risk of
      vitamin D deficiency include the elderly, those living indoors or having a
      covered-up style of dress, especially dark-skinned immigrants, and pregnant
      women, and these are groups recognized as being at increased risk of diabetes.

PMID- 9624223
TI  - Metal (molybdenum, copper) accumulation and retention in brain, pituitary and
      other organs of ammonium tetrathiomolybdate-treated sheep.
AB  - Ammonium tetrathiomolybdate (TTM) is the treatment of choice for chronic Cu
      poisoning in sheep and is recommended in Wilson's disease. However, the long-term
      effects have not been fully evaluated and some evidence questions the long-term
      safety of the drug. The aim of the present study was to investigate the systemic
      distribution and retention of Cu and Mo in TTM-treated sheep of different breeds
      and Cu status. Low-Cu Cambridge sheep were divided into a TTM trial group (3.4
      mg/kg, subcutaneously, on three alternate days per month, for 5 months) and a
      control group, and were killed at the end of the course or 7 months later. High
      Cu sheep consisting of a Cu-supplemented (150 mg/kg) Cambridge group and a North
      Ronaldsay group were administered TTM as before and compared with untreated
      controls. Brain, liver, kidney, heart, skeletal muscle, pituitary, adrenals,
      tests and ovaries were retained for metal analysis. Mo accumulated in all organs
      including brain and pituitary (P < 0.02) in all TTM trial groups and was retained
      after cessation of treatment, except in liver, kidney and skeletal muscle. Cu was
      increased (P < 0.02) and retained in the cerebellum and medulla oblongata in the
      TTM-treated high-Cu Cambridge groups. Brain Cu v. Mo concentrations showed a
      strongly positive correlation (r. 0.7) in the high-Cu Ronaldsay group 7 months
      after TTM treatment. It is concluded that TTM is not all excreted but (Mo) is
      widely distributed and retained in many organs including brain and pituitary. In
      addition TTM may redistribute some displaced excess liver Cu (Cu-TTM) to the
      brain. The consequences of these disturbances await clarification.

PMID- 9624224
TI  - No evidence for an ethnic influence on basal metabolism: an examination of data
      from India and Australia.
AB  - A lower BMR of Indians, when compared with Westerners matched for age, sex and
      either surface area or body weight, has often been reported in the literature and
      has been interpreted to reflect an ethnic influence on BMR. To determine the
      contribution of body composition to these observed differences in BMR, we
      analysed the data on ninety-six Indians and eighty-one Caucasian Australians of
      both sexes, aged 18-30 years, studied in Bangalore, India and Melbourne,
      Australia. Absolute BMR and BMR adjusted for body weight were significantly lower
      in Indians when compared with Australians of the corresponding sex. However, BMR
      adjusted for fat-free mass (FFM) in men, and BMR adjusted for FFM and fat mass
      (FM) in women, were not significantly different between the two groups. Stepwise
      regression of FFM, FM, sex (0 = women; 1 = men) and ethnicity (0 = Indian; 1 =
      Australian) on BMR, resulted in the following relationship for the combined data
      on all subjects: BMR = 88.7 x FFM (kg) + 1713 (n 177; r 0.92; r2 0.85; SEE 425
      kJ). The Indian equations of Hayter & Henry (1994), based on body weight,
      resulted in a significant bias (measured-predicted BMR) of 318 (SE 54) kJ/d in
      Indian men and -409 (SE 70) kJ/d in Indian women. The equation of Cunningham
      (1991), based on FFM, accurately predicted the BMR of Indian men, Indian women
      and Australian men. The small but significant bias of 185 (SE 61) kJ/d in
      Australian women, may be explained by the significant contribution of FM to BMR
      in this group. The present study does not provide any evidence for an ethnic
      influence on basal metabolism. The results strongly support the use of FFM,
      rather than body weight, for the prediction of BMR in population groups of
      varying body size and composition. This would allow an accurate estimation of BMR
      and hence energy requirements in population groups worldwide.

PMID- 9624225
TI  - The effect of dietary sodium intake on biochemical markers of bone metabolism in
      young women.
AB  - To investigate the effect of a low (80 mmol/d) or high (180 mmol/d) Na intake for
      14d on biochemical markers of bone turnover in Na-sensitive and Na-non-sensitive
      healthy young women, twenty-nine subjects were screened for responsiveness of
      urinary Ca excretion to increasing dietary Na intake (40, 80, 120 and 200 mmol/d
      for 7 d). In a crossover study, the eight Na-sensitive and eight of the twenty
      one Na-non-sensitive subjects were randomly assigned to diets containing either
      80 or 180 mmol Na/d for 14d followed by crossover to the alternative diet for a
      further 14 d. Dietary Ca was restricted to 12.5 mmol/d throughout. During each
      dietary period, fasting morning first void urine samples (last 3 d) and fasting
      blood serum samples (morning of twelfth day) were collected. Increasing Na intake
      from 80 to 180 mmol/d increased urinary Na about twofold in both the Na-sensitive
      and Na-non-sensitive groups and increased urinary Ca excretion (by 73%) in the Na
      sensitive group only. Biochemical markers of bone resorption (urinary
      pyridinoline and deoxypyridinoline) and bone formation (serum osteocalcin and
      bone-specific alkaline phosphatase; EC 3.1.3.1) were unaffected by increasing
      dietary Na in either group. It is concluded that the Na-induced calciuria
      observed in the Na-sensitive healthy young women did not result in increased bone
      resorption or turnover and, despite restricted Ca intake, adaptation of dietary
      Ca absorption may have compensated for the increased urinary Ca loss.

PMID- 9624226
TI  - Growth and metabolism of fetal and maternal muscles of adolescent sheep on
      adequate or high feed intake: possible role of protein kinase C-alpha in fetal
      muscle growth.
AB  - From days 4-104 of pregnancy, adolescent sheep, weighing 43.7 (SE 0.87) kg were
      offered a complete diet at two different intakes (approximately 5 or 15 kg/week)
      designed to meet slightly, or well above, maternal maintenance requirements. The
      fetal and maternal muscles were taken on day 104 of pregnancy and analysed for
      total DNA, RNA and protein. Ewes offered a high intake to promote rapid maternal
      weight gain, weighed more (76.5 (SE 4.5) v 50.0 (SE 1.7) kg) and had muscles with
      a greater fresh weight, whilst their fetuses had smaller muscles, than those fed
      at a lower intake. Plantaris muscle of the ewes fed at the high intake contained
      more RNA and protein; again the opposite situation was found in the fetal muscle.
      On the higher maternal intakes, the DNA, RNA and protein contents of the fetal
      plantaris muscle were less than in fetuses of ewes fed at the lower intake. To
      investigate the possible mechanisms involved in this decrease in fetal muscle
      mass, cytosolic and membrane-associated muscle proteins were subjected to Western
      immunoblotting with antibodies to nine isoforms of protein kinase C (PKC), a
      family of enzymes known to play an important role in cell growth. Five PKC
      isoforms (alpha, epsilon, theta, mu, zeta) were identified in fetal muscle. One
      of these, PKC-alpha was located predominantly in the cytosolic compartment in the
      smaller fetuses of the ewes fed at a high plane of nutrition, but was present to
      a greater extent in the membranes of the more rapidly growing fetuses of the ewes
      fed at the lower intake. This was the only isoform to demonstrate nutritionally
      related changes in it subcellular compartmentation suggesting that it may mediate
      some aspects of the change in fetal growth rate.

PMID- 9624227
TI  - Maternal nutrition in early-mid gestation and placental size in sheep.
AB  - We investigated the influence of restricted maternal nutrition between 30 and 80
      d gestation on placental growth. Singleton-bearing ewes were fed on either 0.6
      (i.e. nutrient restricted) times their energy requirements of 2.25 times this
      amount (i.e. controls) up to 80 d gestation, when their placentas and fetuses
      were sampled and analysed. Nutrient-restricted ewes lost body condition score but
      not body weight and had lower plasma thyroid hormone concentrations than
      controls, but there were no differences in plasma glucose, non-esterified fatty
      acids or 3-hydroxybutyrate concentrations between groups. There was no effect of
      maternal nutrient restriction on fetal weight, conformation or organ weight with
      the exception of brain weight which was lower nutrient-restricted ewes. Nutrient
      restriction had no effect on total placental weight, or proportion of inverted
      placentomes, but was associated with an increased abundance of small placentomes
      and decreased weight of the fetal but not maternal components of the placenta.
      Fetal cotyledons form nutrient-restricted ewes also had a lower DNA but higher
      haemoglobin concentration than those sampled from controls. The plasma
      concentration of triiodothyronine in umbilical cord plasma was also increased in
      fetuses from nutrient-restricted ewes. In conclusion, maternal nutrient
      restriction during early-mid gestation is associated with a smaller placenta.

PMID- 9624228
TI  - Glutamine metabolism in the gastrointestinal tract of the rat assess by the
      relative activities of glutaminase (EC 3.5.1.2) and glutamine synthetase (EC
      6.3.1.2).
AB  - The activities of the two key enzyme involved in glutamine metabolism,
      glutaminase (EC 3.5.1.2) and glutamine synthetase (EC 6.3.1.2), have been
      measured in the various tissues of the gastrointestinal (GI) tract of the rat,
      from the mouth to the rectum. Glutaminase activity was particularly high in the
      mucosa of the small intestine, where its activity accounted for more than 80% of
      the total activity of the GI tract. In contrast, the mouth and oesophagus had
      very low activities, accounting for less than 2% of the total. Glutamine
      synthetase was mainly confined to the lower part of the stomach, which accounted
      for almost 90% of the total activity of the GI tract. Activity in the small
      intestine was very low, accounting for less than 2% of the total, and similarly
      low levels were found in the mouth and oesophagus. The data provide the most
      complete information on the distribution of these enzymes in the GI tract of the
      rat and suggest: (a) that the mucosa of the small intestine has the highest
      capacity for glutamine breakdown but the lowest capacity for its synthesis, and
      so requires an external source of this amino acid; (b) that there is little
      potential for glutamine synthesis or breakdown in the mouth and oesophagus: and
      (c) that the lower stomach has a substantial capacity to synthesize glutamine, in
      contrast to the rest of the GI tract. The results of the investigation are
      relevant to sites of glutamine metabolism in therapeutic studies involving
      glutamine administration discussed with reference to reports of the effects of
      glutamine administration on GI tract injury.

PMID- 9624229
TI  - Urinary excretion of purine derivatives as an index of microbial-nitrogen intake
      in growing rabbits.
AB  - Three experiments were carried out to establish a response model between intake
      and urinary excretion of purine compounds. In Expt 1 the relationship between the
      intake of purine bases (PB) and the excretion of total purine derivatives (PD)
      was determined in seven growing rabbits with a mean initial live weight (LW) of
      2.03 (SE 0.185) kg, aged 70 d, each fitted with a wooden neck collar to prevent
      caecotrophagy. They were fed on five experimental diets formulated with different
      levels of nucleic acids (0.00, 3.75, 7.50, 11.25, 15.00 g yeast-RNA/kg diet). The
      relationship between intake of purine (x, mumol/kg W0.75) and total urinary PD
      excretion (y, mumol/kg W0.75), y= 0.56 + 0.67x (r2 O.86; RSD 0.338), indicated
      that about 70% of duodenal PB were recovered as urinary PD and that the
      endogenous contribution was constant and independent of dietary PB supply.
      Endogenous excretion of PD (allantoin and uric acid) was measured in a second
      experiment using six rabbits fed on a purine-free diet and fitted with neck
      collars to avoid caecotrophagy. Basal daily urinary excretion values for
      allantoin and uric acid were 532 (SE 33.9) and 55 (SE 7.3) mumol/kg W0.75
      respectively; xanthine and hypoxanthine were not found in urine samples and
      therefore the sum of allantoin and uric acid should comprise the total excretion
      of PD (588 (SE 40.1) mumol/kg W0.75). The xanthine oxidase (EC 1.2.3.2) activity
      in plasma, liver, duodenum, jejunum and kidney was measured in a third
      experiment. The activities of xanthine oxidase in duodenal and jejunal mucosa,
      liver and kidney were: 0.61 (SE 0.095), 0.37 (SE 0.045), 0.035 (SE 0.001) and 0
      units/g fresh tissue respectively and in plasma 2.96 (SE 0.094) units/1. The
      results show that urinary excretion of PD may be a useful tool to estimate
      duodenal PB input and microbial protein intake once the relationship between PB
      and N has been established in caecal micro-organisms.

PMID- 9624230
TI  - Metabolism of parenterally administered fat emulsions in the rat: studies of
      fatty acid oxidation with 1-13C- and 8-13C-labelled triolein.
AB  - To reassess the hypothesis that fatty acid catabolism occurs to completion via
      beta-oxidation, male Sprague-Dawley rats receiving continuous total parenteral
      nutrition (TPN) including 43% energy as fat were infused with [1-(13)C]- or [8
      (13)C]triolein. Expired CO2 was collected continuously for 4 h and its 13C:12C
      ratio determined by isotope-ratio mass spectrometry. Bicarbonate retention was
      also assessed over 4 h by infusion of NaH14CO3 and measurement of the expired
      14CO2. A possible loss of label from [8-(13)C]oleic acid from the citric acid
      cycle via labelled acetyl-CoA without oxidation to CO2 was assessed by infusing
      further animals with acetate labelled with 14C either at C atoms 1 or 2 and
      determination of its conversion to expired 14CO2. At isotopic steady state, 63.2
      (SE 1.6)% (n 8) of the infused [1-(14)C]acetate and 46.0 (SE 1.2)% (n 8) of [2
      (14)C]acetate was recovered as expired 14CO2. After correction for bicarbonate
      retention and non-oxidative isotope loss, 37.3 (SE 1.2)% (n 20) of the [1
      (13)C]triolein was found to have been oxidized, whereas 32.6 (SE 1.0)% (n 20) of
      the [8-(13)C]triolein was oxidized (P < or = 0.01). The lower oxidation of the C
      atom at position 8 of oleic acid than that at position 1 indicates incomplete
      oxidative breakdown of the fatty acid after entering beta-oxidation.

PMID- 9624232
TI  - Patient 'non-compliance' and 'missing data' in quality of life research: where
      does the problem lie?

PMID- 9624231
TI  - Dietary lipids and evolution of the human brain.

PMID- 9624233
TI  - Should-alpha-interferon be included as standard treatment in multiple myeloma?

PMID- 9624234
TI  - Endocrine treatment of hepatocellular carcinoma. Any evidence of benefit?
AB  - In the past 20 years, a number of studies have investigated the relationship
      between sex hormones and liver cancer. Experimental studies indicate that a
      dynamic process, with sequential modifications in the pattern of sex hormones in
      the serum and of sex hormone receptors in the liver, occurs progressively during
      hepatocarcinogenesis. Overall, it seems that both androgens and oestrogens may
      enhance liver carcinogenesis, while androgens may also support the growth of
      established liver tumours. Unfortunately, clinical studies of endocrine treatment
      of hepatocellular carcinoma (HCC) have not adequately tested the suggestions from
      biological studies. So far, no clinical trial has been performed to test the
      efficacy of endocrine manipulation for the chemoprevention of HCC in cirrhotic
      patients nor in preventing relapse after radical resection of primary HCC. Anti
      oestrogens have been the most studied agents for the endocrine treatment of
      established HCC, although the rationale that supports their use is weaker than
      for anti-androgens. Studies with anti-androgens have produced prevalently
      negative results, due to either a lack of activity or excessive toxicity. The use
      of chemical castration, which theoretically could enhance the activity of
      antihormonal compounds, yielded no benefit at all. In summary, there is, as yet,
      no definitive evidence that endocrine treatment favourably affects the outcome of
      patients with HCC.

PMID- 9624235
TI  - Pharmacokinetics of anticancer agents in patients with impaired liver function.
AB  - This report reviews published information on the clinical pharmacokinetics of
      antitumour agents in patients with liver dysfunction, associated with primary
      liver disease or liver metastases. Information was available for anthracyclines
      and their related compounds, antimetabolites, cyclophosphamide, vinca alkaloids,
      taxanes and epipodophyllotoxins. Changes in the pharmacokinetic profile or
      metabolism in patients with mild or severe hepatobiliary dysfunction are
      described and the relationships between serum levels, parameters employed for
      measuring hepatic function and toxic or therapeutic effects are examined. Current
      knowledge of the pharmacokinetics of antineoplastic agents in liver disease is
      far from complete, mostly obtained in small numbers of non-homogeneous patients
      often presenting only moderate liver dysfunction, and empirical guidelines for
      dose assessment are still largely applied in clinical practice. Because of the
      complex pathophysiological mechanisms of liver insufficiency in cancer patients,
      there is still doubt whether endogenous markers are useful. Although caution in
      treating cancer patients with liver insufficiency is compulsory, for most
      compounds there seems no need to recommend dose reductions for moderate
      impairment. However, for the tubulin acting agents, vincristine, vinblastine and
      possibly for paclitaxel and docetaxel, there is strong evidence that dose
      adjustment is mandatory in order to avoid excessive neutropenia and
      neurotoxicity.

PMID- 9624236
TI  - Surgeons and radiotherapists show 'adverse reaction' to drugs--a report on ECCO9
      14-18 September 1997, Hamburg, Germany.

PMID- 9624237
TI  - Survey of the Administration of quality of life (QL) questionnaires in three
      multicentre randomised trials in cancer. The Medical Research Council Lung Cancer
      Working Party the CHART Steering Committee.
AB  - We surveyed centres collaborating in two trials in lung cancer (LU12, LU13) and
      one in lung and head and neck cancer (CHART) to find out how QL questionnaires
      were being administered, with the aim of standardising procedures and improving
      compliance. Dedicated local trials staff were funded for CHART but not for the
      other trials. In all three trials, patients completed a Rotterdam Symptom
      Checklist (RSCL) and a Hospital Anxiety and Depression Scale (HADS) at specified
      times. 17 of 22 LU12 centres, 9 of 11 LU13 and all 10 CHART centres returned
      survey forms. In LU12 and LU13, the category of staff responsible for
      questionnaires varied widely; in CHART, only research staff were involved. This
      led to more consistency in CHART centres in the administration and collection of
      questionnaires, and more frequent checking of forms. However, even the CHART
      administration, although better than in the other two trials, could not be
      regarded as standardised. All centres were equally affected by logistical
      problems. These embraced organisational deficits (e.g. unavailability of staff,
      lack of questionnaires) and patient-related factors (e.g. patient deemed to be
      too ill, had difficulty reading or left before completing the form). Patient
      refusals were an uncommon reason for non-compliance and patients were considered
      to be generally in favour of QL assessment. As a result of these findings, a
      number of measures have been put in place to increase standardisation of
      procedures and improve compliance. These include publishing guidelines for
      protocol writing, providing centres with guidelines for QL administration and
      information leaflets for patients, together with introducing staff training.

PMID- 9624238
TI  - Obvious peritumoral emboli: an elusive prognostic factor reappraised.
      Multivariate analysis of 1320 node-negative breast cancers.
AB  - This study was conducted to determine the prognostic influence of obvious
      peritumoral vascular emboli as prospectively determined by a simple routine slide
      examination in patients with operable node-negative breast cancer. Obvious
      peritumoral emboli (OPE) were defined by the presence of neoplastic emboli within
      unequivocal vascular lumina (including both lymphatic spaces and blood
      capillaries) in areas adjacent to but outside the margins of the carcinoma. OPE
      were assessed routinely on 5 microns thick haematoxylin and eosin-stained
      sections for each of 1320 primary operable node-negative breast cancers from 1975
      to 1992 at our institution. OPE and other prognostic variables (tumour size, SBR
      grade, oestrogen and progesterone receptor status) were correlated to overall
      survival (OS) and metastasis-free interval (MFI) by means of univariate and
      multivariate analysis with a median follow-up of 103 months. OPE were found in
      19.5% of tumours. In univariate analysis, OPE were related to tumour size (P =
      6.3 x 10(-5)) and histologic grade (P = 4.9 x 10(-7)). Statistically significant
      correlations were found with OS (P = 4.6 x 10(-5)) and MFI (P = 6.4 x 10(-9)).
      Furthermore, in multivariate analysis, OPE was an independent prognostic
      variable, the most predictive factor for MFI (P = 7.7 x 10(-7)) before tumour
      size and grade, and was second after tumour grade for OS (P = 0.002). This study
      on a large unicentric series and with a long follow-up confirms the prognostic
      significance of vascular emboli in patients with operable node-negative breast
      carcinoma. Importantly, vascular emboli were found to be accurately detectable by
      a simple routine and non-time-consuming method. Therefore, such obvious vascular
      emboli should be considered as an important cost-effective, prognostic variable
      in patients with node-negative breast carcinoma.

PMID- 9624240
TI  - Risk factors of pneumonitis following chemoradiotherapy for lung cancer.
AB  - The purpose of this retrospective study was to identify risk factors associated
      with development of pneumonitis following chemoradiotherapy (CRT). We examined 60
      patients (pts) who received CRT from May 1993 to August 1995. Factors evaluated
      included total radiation dose, field-size, irradiated site, type of chemotherapy,
      pulmonary fibrosis and treatment schedule (concurrent versus sequential). There
      were 17 pts (28.3%) who had > or = Grade 2 pulmonary toxicity. There was no
      significant relationship between total radiation dose, field-size > or = 200 cm2,
      pulmonary fibrosis or treatment schedule and risk of pneumonitis. In the
      sequential treatment group (22 pts), no relationship was noted between any factor
      and the risk of pneumonitis, while in the concurrent treatment group (38 pts),
      the incidence of pneumonitis was more frequent (53.8%) in patients with field
      size > or = 200 cm2 than in patients with field-size < 200 cm2 (P < 0.05). In
      those who received concurrent treatment, including weekly CPT-11, pneumonitis was
      more frequent (56.3%) than in those without CPT-11 (13.6%, P < 0.01). When the
      lower lung field was included in the radiation site, the incidence of pneumonitis
      was 70% compared with 20% for other sites (P < 0.01). Multivariate analysis
      revealed a significant relationship between radiation site and the risk of
      pneumonitis (P = 0.0096). CPT-11 was significant (P = 0.038) only in the
      concurrent group. Pneumonitis was reversible in all but one pt by steroid
      therapy. Thus, irradiated site (included lower lung field) and concurrent CRT
      used with weekly CPT-11 were treatment factors significantly associated with a
      higher risk of pneumonitis following CRT.

PMID- 9624239
TI  - Very low-dose adjuvant chemotherapy in steroid receptor negative stage I breast
      cancer patients. Austrian Breast Cancer Study Group.
AB  - A randomised clinical trial was performed to test whether or not low-dose
      chemotherapy lasting only 35 days improves the outcome of breast cancer patients
      with stage I disease and negative oestrogen and progesterone receptors (ER-, PgR
      ). Between 1984 and 1990, 277 stage I breast cancer patients with tumours
      negative for both oestrogen and progesterone receptors were randomised to receive
      either low-dose short-term chemotherapy or no chemotherapy. Chemotherapy
      consisted of one cycle of doxorubicin, vincristin (AV) and one cycle of
      cyclophosphamide, methotrexate, fluorouracil (CMF). Patients were stratified for
      tumour stage, type of surgery, menopausal status and participating centre.
      Results were analysed both by univariate and multivariate statistical. After a
      median length of follow-up of 84 months, disease-free (DFS) and overall survival
      (OS) did not differ significantly between patients having received adjuvant
      chemotherapy and the control group. Uni- and multivariate analysis did not show
      any significant prognostic or therapy related factor. A low-dose short-term
      adjuvant chemotherapy is insufficient to improve the prognosis of patients with
      breast cancer stage I with ER-, PgR-tumours.

PMID- 9624241
TI  - Microalbuminuria in patients with lung cancer.
AB  - In a prospective study of 102 outpatients with histologically proven lung cancer,
      the prevalence and prognostic significance of microalbuminuria (urinary albumin
      excretion > 20 micrograms/min) were analysed. 65 consecutive outpatients with
      benign lung disorders served as controls. An immunoturbidimetric assay, sensitive
      at low concentrations, was used to quantify the albumin excretion rate in timed
      overnight urine samples. Patients with malignancies had a significantly higher
      frequency of microalbuminuria (32.4% compared with controls, 13.8%, P < 0.01) and
      median urinary albumin excretion rate (13.4 versus controls, 8.9 micrograms/min,
      P < 0.003). Urinary albumin excretion was significantly higher in lung cancer
      patients with TNM stage III and IV. Patients with malignancies and
      microalbuminuria had a significantly lower survival rate than patients with
      normoalbuminuria (probability of survival 1 and 3 years after diagnosis 66% and
      16% versus controls, 22% and 4%, P < 0.00001). In a multivariate model, which
      adjusted for age, sex, performance status, histological type and TNM stage,
      microalbuminuria continued to be a significant predictor of survival. In
      conclusion, an increased prevalence of microalbuminuria has been demonstrated in
      patients with lung cancer. The presence of microalbuminuria was associated with
      advanced disease stage and poor survival.

PMID- 9624242
TI  - Expression of the multidrug resistance protein (MRP) in squamous cell carcinoma
      of the oesophagus and response to pre-operative chemotherapy.
AB  - One of the major problems in the treatment of squamous cell carcinoma of the
      oesophagus (ESCC) is the unresponsiveness to cytotoxic drugs. So far, the
      mechanisms underlying the intrinsic drug resistance of ESCC remain unclear. The
      aim of this study was to determine the role of the newly recognised drug
      resistance protein, the multidrug resistance protein (MRP), in ESCC drug
      resistance. Tumour biopsies from ESCCs were analysed by RNase protection assay
      (RPA) as well as by immunohistochemistry (IHC) for the presence of MRP mRNA or
      protein, respectively. The ESCC samples were obtained from patients participating
      in a prospective randomised clinical phase III trial, evaluating pre-operative
      chemotherapy (cisplatin and etoposide) followed by surgery versus surgery alone
      in patients with operable ESCC. For most patients, tumour biopsies taken at
      diagnosis by endoscopy as well as surgically resected primary tumours were
      available. Of 58 ESCC patients enrolled, 28 received chemotherapy before surgical
      resection of their tumours, and 30 were treated with surgery alone. 12 patients
      (3 complete and 9 partial responses; 43%) showed a major response after
      chemotherapy, 10 patients (36%) had stable disease (SD), and 6 (21%) progressive
      disease (PD). On 14 surgically resected, untreated, primary ESCCs, the IHC scores
      correlated with the MRP mRNA levels, quantitated by RPA (multiple testing, P <
      0.01). MRP expression was detected by IHC in the vast majority (52/58; 90%) of
      the diagnostic biopsies. MRP expression did not differ significantly between CR +
      PR, and patients with SD or PD. In addition, multivariate analysis by logistic
      regression did not show any effect of tumour cell differentiation or UICC tumour
      stage on the outcome of pre-operative chemotherapy in relation to MRP expression.
      However, a difference became apparent (Sign-test, P < 0.05) for higher MRP
      expression in tumours from patients with PR or SD, when comparing MRP levels in
      paired tumour samples before and after chemotherapy, suggesting that chemotherapy
      selected for drug-resistant cell clones.

PMID- 9624243
TI  - Phase I pharmacological study of intra-arterially infused fotemustine for
      colorectal liver metastases.
AB  - Fotemustine was investigated in 17 patients with progressive hepatic metastases
      from colorectal carcinoma to define the maximally tolerated dose for a daily
      hepatic intra-arterial infusion (HAI) schedule. Haematotoxicity was delayed, dose
      dependent and related to pretreatment, with thrombo- and leucocytopenia being
      dose-limiting. Local side-effects at the liver were mild. Infection (WHO grade
      III) occurred in 1 patient due to neutropenia. Other side-effects, particularly
      renal, pulmonal, neurological or cardiac toxicity, mucositis and diarrhoea, hair
      loss or allergic reactions did not occur. Pharmacokinetic analysis indicated a
      short plasma half-life (t1/2 = 25.8 +/- 11.5 min) and a high body clearance (CL =
      2193 +/- 870 ml/min) with large inter- and intra-individual variations. Of 15
      evaluable patients, one complete and three partial responses were observed (ORR =
      27%; CI95% [4.5-49.5%]). All tumour remissions appeared at higher dose levels in
      previously untreated patients. Considering the absence of mucosal side-effects,
      such as mucositis/diarrhoea and of hepatic toxicity, this agent was well
      tolerated. The recommended intra-arterial dose for consecutive phase II trials is
      125 mg/m2/day1-3.

PMID- 9624244
TI  - Co-variables influencing 5-fluorouracil clearance during continuous venous
      infusion. A NONMEM analysis.
AB  - The objective of this study was to attempt to identify patient co-variables which
      could influence interpatient variability in 5-fluorouracil (5-FU) clearance
      during a 5-day continuous venous infusion (CVI, cisplatin 100 mg/m2 day 1 then 5
      FU 1 g/m2/day days 2-6). The analysis was performed using a NONMEM program
      according to a linear one-compartment model. A total of 186 cycles (2 samples per
      day, 8 a.m. and 5 p.m.) were analysed from 104 patients with various cancers (the
      majority of head and neck and oesophagus). The study co-variables were age, sex,
      body surface area, hepatic metastases, peripheral mononuclear cell
      dihydropyrimidine dehydrogenase activity (PMNC-DPD), liver enzymes, clock-time (8
      a.m. versus 5 p.m.), elapsed time during CVI. The data showed that 5-FU clearance
      was significantly reduced by increased age, low PMNC-DPD, high serum alkaline
      phosphatase and elapsed time during infusion. These data may be useful for
      improving knowledge of predictive factors which can influence 5-FU exposure and
      thus predispose to toxic manifestations.

PMID- 9624245
TI  - Prevalence and prognostic significance of epilepsy in patients with gliomas.
AB  - The aim of this study was to evaluate the prevalence and prognostic significance
      of epilepsy in 1028 patients diagnosed in the computer tomography (CT) era with
      histological low- or high-grade intracranial gliomas. Survival analysis included
      Kaplan-Meier plots, log-rank tests, logistic regression and Cox's analysis as
      implemented in the SPSS statistical package. Epilepsy was a positive univariate
      (P < 0.0001) and multivariate, (P < 0.03) prognostic factor for survival in the
      total patient group (n = 1028, relative risk of death 0.83, 95% confidence
      interval (CI) 0.70-0.98) as well as in the high-grade patient group (n = 649,
      relative risk of death 0.80, 95% CI 0.66-0.96), but not in the group of low-grade
      glioma patients (P > 0.2). The prevalence of epilepsy in glioblastoma patients
      was 251/512 (49%), 95/137 (69%) in anaplastic gliomas, and 322/379 (85%) in
      patients with low-grade gliomas, with 97 of the 102 T1 low-grade subgroup (95%)
      having epilepsy, indicating that the presence of epilepsy may select patients for
      early radiological diagnosis. The frequency of epilepsy at presentation decreased
      with age in high-grade glioma patients, and increased with age in low-grade
      glioma patients to a plateau in the fourth decade of life (P < 0.01). The
      prevalence of epilepsy in patients with histological intracranial gliomas varied
      with patient age and tumour histology, with low-grade patients having the highest
      prevalence. Epilepsy was a significant positive prognostic factor except in
      patients with low-grade gliomas, and may select low-grade patients for early
      diagnosis.

PMID- 9624246
TI  - Germ cell tumours of the central nervous system: treatment consideration based on
      111 cases and their long-term clinical outcomes.
AB  - Germ cell tumours (GCTs) of the central nervous system (CNS) encompass various
      histological subtypes, and their optimal management has been the subject of
      debate. To indicate a better management strategy for each subtype, we analysed
      the records of 111 patients (median age 14 years), who underwent treatment since
      1970. With a median follow-up duration of 86 months, the probability of surviving
      5 years was: 96% for pure germinoma patients, 100% for mature teratoma, 67% for
      immature teratoma and 69% immature teratoma mixed with germinoma. The probability
      of cause-specific progression of germinomas producing human chorionic
      gonadotropin (HCG) was higher than that of non-producing germinomas (P < 0.01).
      GCTs that included a highly malignant component, such as embryonal carcinoma or
      yolk sac tumour, exhibited a poor prognosis with 38% chance of 5-year survival.
      Late adverse effects of therapy included stroke, secondary malignancy and
      cognitive, endocrinological, auditory and visual dysfunctions. Of 85 survivors
      with a median follow-up period of 99 months, 58 patients needed hormone
      replacement therapy, 26 patients showed poor performance status and, to date,
      only 1 patient has fathered children. Because the outcomes varied widely for each
      subtype, the traditional categories, that is, germinoma and non-germinomatous GCT
      as an extrapolation from the gonadal GCTs, are not suitable for appropriately
      selecting therapeutic regimen for CNS GCTs.

PMID- 9624247
TI  - Retinoid-induced differentiation of neuroblastoma: comparison between LG69, an
      RXR-selective analogue and 9-cis retinoic acid.
AB  - The aim of this study was to investigate in vitro the effects of all-trans
      retinoic acid (RA), 9-cis RA and the RXR-selective analogue, LG69, on the
      morphological differentiation, proliferation and gene expression of neuroblastoma
      cells. Three different cell lines were cultured with the retinoid for either 9
      continuous days or for 5 days followed by 4 days without the retinoid and
      morphological differentiation was assessed both qualitatively and quantitatively.
      SH SY 5Y cell proliferation was examined by measuring cell numbers after exposure
      to the retinoids and RAR-beta gene expression was examined by Northern blot
      analysis. Morphological differentiation was more effectively induced by all-trans
      and 9-cis RA than by LG69. SH SY 5Y cells, when treated with 9-cis RA for only 5
      of the 9 days of culture, underwent apoptosis, but this was not seen with 9 days
      continuous exposure nor with LG69. Inhibition of SH SY 5Y cell proliferation by
      all-trans or 9-cis RA was dose-dependent, but LG69 had little effect. Conversely,
      LG69 induced higher expression of RAR-beta than all-trans RA, but less than that
      produced by 9-cis RA. These data suggest that 9-cis RA as a single agent is the
      most effective modulator of neuroblastoma behaviour and may be the most
      appropriate therapeutic agent.

PMID- 9624248
TI  - Cancer mortality in Europe: effects of age, cohort of birth and period of death.
AB  - Death certification data for 19 cancers or groups of cancers, plus total cancer
      mortality, in 16 major European countries were analysed using a log-linear
      Poisson model with arbitrary constraints on the parameters to disentangle the
      effects of age, birth cohort and period of death. Three major patterns emerged
      including: first, the prominent role of cohort of birth in defining trends in
      mortality from most cancer sites (except testis or Hodgkin's disease, where newer
      treatments had a major period of death effect); and second, the major role of
      lung and other tobacco-related neoplasm epidemics in determining the diverging
      pattern of cancer mortality, for each sex and in various European countries and
      geographic areas. In most countries, the peak male cohort values were reached for
      generations born between 1900 and 1930. This was observed in women only for
      Denmark and the U.K., i.e. the two countries where lung and other tobacco-related
      neoplasm epidemics had already reached appreciable levels. This confirms the
      importance of cigarette smoking in subsequent generations as a major cause of
      cancer deaths in Europe. Further, there is a persistent rise in several cancer
      rates, again chiefly on a cohort basis, in Eastern Europe, which calls for urgent
      intervention to control the cancer burden in these countries.

PMID- 9624249
TI  - Chromosome imbalance at the 3p14 region in human breast tumours: high frequency
      in patients with inherited predisposition due to BRCA2.
AB  - Our previous studies have indicated that genetic aberrations in the 3p14 region
      are more frequent in malignant tumours from hereditary breast cancer patients
      than sporadic breast cancers. The main purpose of this study was to test if BRCA2
      susceptibility alleles contribute to imbalance in the 3p14 region. We mapped
      allelic imbalance at 3p14 in tumours from Icelandic sisters affected with breast
      cancer using a set of 10 microsatellite markers (tel-D3S1295-D3S1234-D3S1300
      D3S1600-D3S1233+ ++-D3S1217-D3S1261-D3S1296-D3S1210- D3S1284-cen). The patients
      were of known carrier status with respect to the 999del5 mutation in BRCA2 which
      is the most common cause of hereditary breast cancer in Iceland. Of 103 patients,
      32 in the group were mutation carriers. A high degree of imbalance was observed
      in tumours from BRCA2 mutation carriers, ranging from 44 to 88% for individual
      markers. This was significantly higher than the percentage of imbalance in
      tumours from non-carriers, where the frequency ranged from 25 to 43%. In both
      groups, we noted elevated 3p14 imbalance in patients with bilateral disease.
      Allelic imbalance was most commonly observed near the marker D3S1210 (3p14.1-p12)
      and the FHIT gene (3p21.1-p14.2) for both groups. We conclude that genomic
      aberrations in 3p14 are especially frequent in tumours with BRCA2 gene defects,
      and suggest that this is caused by regional loss of chromosome stability rather
      than selection.

PMID- 9624250
TI  - Intraperitoneal cisplatin with regional hyperthermia in advanced ovarian cancer:
      pharmacokinetics and cisplatin-DNA adduct formation in patients and ovarian
      cancer cell lines.
AB  - The purpose of this study was to investigate the influence of hyperthermia on
      cisplatin pharmacokinetics and DNA adduct formation. The latter was investigated
      both in tumour cell lines in vitro and in tumour cells and buccal cells from
      cancer patients. The patients had advanced ovarian carcinoma and were entered
      into a phase I study for cytoreductive surgery followed by hyperthermia in
      combination with intraperitoneal cisplatin administration. The cisplatin-DNA
      modifications in vivo and in vitro were studied by an immunocytochemical method
      with the polyclonal antiserum NKI-A59. The patient samples for pharmacokinetic
      determinations were analysed by flameless atomic absorption spectrometry. In
      vitro, the combination of hyperthermia and cisplatin enhanced cell killing
      compared with either treatment alone, such that the cisplatin-resistant ovarian
      cell line A2780/DDP became almost as sensitive as the parent A2780 cell line
      (resistance factor reduced from 30 to 2 at the IC50). In addition, increased
      cisplatin-DNA adducts were observed in the resistant cell line after the combined
      treatment compared with cisplatin alone. A good correlation was found between
      nuclear staining density and surviving fraction for all groups, indicating that
      the DNA adducts generated are an important determinant of toxicity and that the
      mechanism by which hyperthermia enhances kill is by increasing adduct levels. In
      the patients, the ratio of drug concentration in the peritoneal perfusate
      compared with that in plasma was found to be approximately 15, indicating a
      favourable pharmacokinetic ratio. Cisplatin-DNA adduct formation in tumour cells
      from patients was higher than in buccal cells, reflecting this higher drug
      exposure, i.e. local plus systemic versus systemic only. In addition, the tumour
      cells but not buccal cells were exposed to hyperthermia. The higher number of
      tumour adducts also suggests that a favourable therapeutic ratio could be
      achieved. Platinum-DNA adduct formation was found to decrease with distance from
      the surface of the tumour nodules. However, at a distance of 3-5 mm, the nuclear
      staining density levels were still measurable and higher than in buccal cells. In
      conclusion, the combined pharmacokinetic and adduct data in patients support the
      advantages of the intraperitoneal route for drug administration, and the addition
      of heat.

PMID- 9624251
TI  - Low toxicity and high antitumour activity of daunomycin by conjugation to an
      immunopotential amphoteric branched polypeptide.
AB  - The acid labile derivative of Daunomycin cis-aconityl Daunomycin (cAD), was
      coupled to an amphoteric polypeptide, poly[Lys-(Glui-DL-Alam)] (EAK), which was
      selected for conjugation on the basis of its pharmacological and immunological
      properties. The systemic toxicity of covalently attached Daunomycin was studied
      by monitoring body weight, life-span, bone marrow and haematological parameters
      of BDF1 mice. More than 3-fold the lethal dose of free Daunomycin could be
      applied without serious toxic effect when the drug was attached to EAK. The dose-
      and time-dependent modulatory effect of free drug and [cAD]-EAK conjugate on the
      humoral and cellular immune response to sheep red blood cell antigens in mice was
      studied. The conjugation of Daunomycin to EAK carrier polypeptide compensated for
      the immunosuppression induced by free Daunomycin. [cAD]-EAK conjugate at
      Daunomycin doses of 2-10 mg/kg was very effective against L1210 leukaemia
      producing 66-100% long-term survivors (> 60 days), while Daunomycin in itself
      increased the mean survival only by 52%, with no long-term survivors. The mixture
      of free Daunomycin and EAK polypeptide had similar toxicity and antitumour
      activity as free Daunomycin, indicating the important role of covalent attachment
      in increased therapeutic efficacy.

PMID- 9624252
TI  - Inhibition of fibroblast collagen synthesis and proliferation by levamisole and 5
      fluorouracil.
AB  - Experimental studies indicate that anastomotic healing in the intestine is
      compromised by the immediate postoperative administration of 5-fluorouracil and
      levamisole. Since fibroblast functions are crucial to healing, we investigated
      the effects of (combinations of) both drugs on proliferation and collagen
      synthesis of rat skin fibroblasts in vitro. Proliferation was measured in
      actively dividing cells by cellular [3H]thymidine uptake and collagen synthesis
      in non-dividing cells by [3H]proline incorporation into collagenase-digestible
      protein. 5-Fluorouracil strongly and significantly (P < 0.05) reduced DNA
      synthesis and collagen synthesis at concentrations of 1 microM or more. The
      latter effect was not specific for collagen since total protein production was
      affected similarly. Both effects depended on the duration of exposure to the
      drugs. Levamisole also inhibited fibroblast proliferation dose-dependently, but
      less effectively than 5-fluorouracil: 50% inhibition was observed at
      approximately 0.1 mM. Collagen synthesis was unaffected by levamisole. If
      levamisole was added together with a low (0.1 microM) concentration of 5
      fluorouracil, which in itself did not decrease thymidine incorporation,
      levamisole's antiproliferative effects became apparent at concentrations as low
      as 1 microM. A similar effect, but at a much higher concentration (1 mM) was
      noted on fibroblast collagen synthesis. These results indicate that levamisole
      potentiates 5-fluorouracil effects in fibroblast cultures and that direct effects
      of these drugs, alone or in combination, on fibroblast proliferation and collagen
      synthesis may be responsible for their negative influence on wound repair.

PMID- 9624253
TI  - In vitro modulation of doxorubicin and docetaxel antitumoral activity by methyl
      beta-cyclodextrin.
AB  - Methyl-beta-cyclodextrin (MEBCD) was investigated for its effect on the
      antitumoral activity of various antineoplastic agents (doxorubicin (DOX),
      docetaxel (DXL), 5-fluorouracil (5-FU) and cisplatin (CDDP)) in three different
      human parental sensitive cancer cell lines (K562 S, MCF7 S and A2780 S) and their
      multidrug resistant variant sublines (K562 R, MCF7 R and A2780 R). At non
      cytotoxic concentrations, MEBCD was able to increase significantly DOX and DXL
      cytotoxic activity in all the cell lines tested. The sensitisation ratios (IC50
      drug control/IC50 drug-MEBCD treated) ranged from 3l1 to 14.3. Moreover,
      intracellular DOX accumulation, determined by high-performance liquid
      chromatography, was also increased when cells were treated with MEBCD combined
      with DOX (approximately 2-3 fold). The effects of MEBCD in resistant sublines
      were greater than in their parental sensitive cell lines. Other experiments
      demonstrated that the action of the MEBCD was independent of DOX. These data
      provided a basis for the potential therapeutic application of MEBCD in cancer
      therapy.

PMID- 9624254
TI  - The DNA content of chromosome division figures and interphase nuclei classifies
      ulcerative colitis.
AB  - Long-standing ulcerative colitis is considered to be a precancerous condition.
      Therefore, a practical and reliable method is required for monitoring the
      progress of the disease. Liberation of the S-phase from karyokinesis occurs in
      DNA amplification and endoreplication, producing nuclei with more than 4 c DNA.
      The amount of Feulgen DNA was quantified with an image microphotometer in 8
      microns sections for interphase nuclei and in 15 microns sections for chromosome
      division figures (CDFs). Development of ulcerative colitis was investigated in
      low grade dysplasia (n = 93 cases; score 3-7) and high grade dysplasia (n = 22;
      score 8-10). Bacterial colitis (n = 34) and invasive adenocarcinoma (n = 26)
      provided a basis for data interpretation in dysplasia. Lymphocyte nuclei served
      as an internal DNA standard. CDFs represent a novel type of aberrant 'mitoses';
      they are different from and much more frequent than figures with multipolar
      spindles. Endoreplication began with low grade dysplasia in interphase nuclei as
      well as with CDFs; it was fully established in high grade dysplasia and
      carcinoma. Endoreplicated interphase nuclei and CDFs represent an early
      morphological mosaic of genomic instability. Both characteristics support a
      reproducible two-level classification of low and high grade dysplasia in
      ulcerative colitis.

PMID- 9624255
TI  - A clinically applicable assay for tumoral thymidylate synthase combining reverse
      transcriptase-PCR and high-performance liquid chromatography.
AB  - The main clinically relevant cellular target of 5-fluorouracil (5-FU) is the
      enzyme thymidylate synthase (TS). Both preclinical data and clinical data in
      digestive tract cancer indicate that an increased amount of TS in tumours can
      predict for 5-FU resistance. We developed an automated method combining the
      principle of RT-PCR coupled with HPLC separation and quantification. The RT-PCR
      HPLC method was applied to TS determination in tumoral biopsies from patients
      with colorectal cancer. The PCR samples were separated and quantified using a
      polystyrene divinylbenzene C 18 column. Within 22 min, it was possible to elute
      18 peaks representing DNA sizes ranging from 34 to 622 bp. Both separation and
      quantification of beta 2 microglobulin (beta 2m, internal standard) and TS PCR
      products were achieved in approximately 10 min per sample. Validation of the RT
      PCR HPLC method was established by comparing RT-PCR quantification of TS after
      electrophoresis and HPLC and by comparing the RT-PCR quantification of TS after
      HPLC with the classical biochemical method. The proposed HPLC method offers a 10
      50 fold sensitivity advantage over electrophoresis. In addition, this RT-PCR HPLC
      procedure allows not only the quantification of TS expression but also the direct
      collection of unaltered amplified DNA sequence which could be useful for
      sequencing analysis, since TS mutations have been described. The present RT-PCR
      HPLC method for determining TS expression in tumoral biopsies is a valuable
      analytical approach as it is specific, sensitive and clinically applicable.

PMID- 9624256
TI  - Growth inhibitory effect of lithium gammalinolenate on pancreatic cancer cell
      lines: the influence of albumin and iron.
AB  - Essential fatty acids, especially gamma linolenic (GLA) and eicosapentaenoic
      acids, have been proposed as potential anticancer drugs. Our aim was to study the
      effect of the lithium salt of gamma linolenic acid (LiGLA) on the growth of two
      human pancreatic cancer cell lines (MIA PaCa2 and Panc 1) and primary human
      fibroblasts (HFF 5) in vitro. Cell growth was assessed by a microculture
      tetrazolium (MTT) assay. LiGLA had a selective growth inhibitory effect on
      pancreatic cancer cell lines with 50% growth inhibition (IC50) at approximately 6
      16 mumol/l compared with approximately 111 mumol/l for the fibroblasts. The
      degree of growth inhibition increased with the time of exposure to LiGLA. Special
      attention was paid to the influence of albumin and iron on LiGLA-mediated growth
      inhibition. Albumin incorporated into essentially serum-free culture medium
      inhibited the effect of LiGLA in a dose-dependent manner, associated with reduced
      GLA uptake by cancer cells. Ferric ions were confirmed as potentiators of the
      growth inhibitory effect of LiGLA but more physiologically relevant transferrin
      bound iron was ineffective. With further improvements in the fatty acid delivery
      mechanism, LiGLA may become a useful adjunct in the management of pancreatic
      cancer patients.

PMID- 9624257
TI  - Randomised double-blind study comparing tropisetron alone and in combination with
      dexamethasone in the prevention of acute and delayed cisplatin-induced emesis.
AB  - In a randomised, double-blind and parallel-design multicentre study, 282
      chemotherapy-naive cancer patients received tropisetron 5 mg intravenously (i.v.)
      before high-dose cisplatin on day 1, and oral tropisetron 5 mg daily on days 2-6,
      in combination with either placebo (n = 143) or dexamethasone (n = 135), given
      i.v. on day 1 and orally on days 2-6. Complete protection from acute
      vomiting/nausea was achieved in 76.3%/79.3% of patients receiving the combination
      and in 55.2%/61.5% of those receiving tropisetron alone. Complete protection on
      days 2-6 from delayed vomiting/nausea was obtained in 60%/60% and 39.2%/40.6%,
      respectively. Tropisetron in combination with dexamethasone is safe and more
      effective than tropisetron alone in the prevention of both acute and delayed
      cisplatin-induced emesis.

PMID- 9624258
TI  - Urinary 5-hydroxyindoleacetic acid (5-HIAA) excretion during multiple-day high
      dose chemotherapy.
AB  - Highly emetogenic drugs such as cisplatin induce an increase in the urinary 5
      hydroxyindoleacetic acid (5-HIAA) level, the main metabolite of serotonin (5-HT),
      within the first 24 h following a single infusion, thus providing a possible
      cause for acute emesis and an explanation for the action of 5-HT3 antagonists. No
      further excretion peaks have been observed, suggesting that additional or
      serotonin-independent mechanisms cause delayed emesis. Our aim was to study the
      mechanisms behind emesis seen during a highly emetogenic chemotherapy regimen
      given as a continuous infusion over several days. Seven women treated with a 4
      day high-dose chemotherapy (HDCT) regimen for breast cancer entered the study.
      Pooled urine samples were collected prior to and during chemotherapy for
      determining 5-HIAA excretion. An excretion peak in the urinary 5-HIAA level was
      observed within the first 24 h with no further peaks thereafter. Thus, the
      mechanisms behind the emesis experienced during this highly emetogenic multiple
      day chemotherapy regimen from days 2-3 onwards would appear to be at least
      partially serotonin independent and would not be expected to be completely
      relieved by 5-HT3 antagonists alone.

PMID- 9624259
TI  - Effects of gemcitabine on renal function in patients with non-small cell lung
      cancer.
AB  - Gemcitabine is a novel fluorine-substituted cytarabine (Ara-C) analogue with
      activity against a range of solid tumours. Besides dose-limiting haematological
      toxicity, renal side-effects were observed from phase I and II studies concerning
      elevations of serum creatinine, proteinuria and erythrocyturia. The aim of this
      study was to investigate the effect of gemcitabine on renal function in 11
      untreated patients with non-small cell lung cancer (NSCLC). Gemcitabine was given
      as weekly infusions of 1250 mg/m2 for 3 weeks, followed by 1 week rest. This
      comprised one cycle (maximum of six cycles). The glomerular filtration rate (GFR)
      and effective renal plasma flow (ERPF) were measured simultaneously with a
      constant infusion of 125I-iothalamate and 131I-hippuran, respectively. Tubular
      damage was monitored by excretion of tubular enzymes (lactic dehydrogenase (LDH),
      alkaline phosphatase (ALP), gamma-glutamyltransferase (GT) and beta 2
      microglobulin); glomerular damage was monitored by excretion of albumin in the
      urine. In 9 patients, the effect of the first infusion was evaluated. After the
      first infusion of gemcitabine, no change was observed in renal function. After
      two, three, and six cycles of treatment, no significant changes in GFR and ERPF
      were noticed in 9 evaluable patients. However, in 3 patients, a decrease in GFR
      of > 10% was observed after multiple cycles. In one of them this was accompanied
      with albuminuria (360 mg/24 h) and erythrocyturia. There were no significant
      changes in urinary excretion of tubular enzymes or albumin. In conclusion, we did
      not observe acute renal toxicity with gemcitabine. No significant cumulative
      effects of gemcitabine on renal function could be detected, although 3 patients,
      treated with multiple cycles of gemcitabine, showed a moderate decrease in renal
      function. Glomerular damage might play a role in the development of renal
      function loss.

PMID- 9624260
TI  - The value of pre-operative lymphoscintigraphy in breast cancer treatment.

PMID- 9624261
TI  - Radioguided surgery of occult breast lesions.

PMID- 9624262
TI  - Chemical pleurodesis with mitoxantrone in the management of malignant effusions.

PMID- 9624263
TI  - Proteinuria: a frequent paraneoplastic phenomenon in colorectal cancer?

PMID- 9624264
TI  - Human effect monitoring in cases of occupational exposure to antineoplastic
      drugs: a method comparison.
AB  - OBJECTIVES: To investigate whether DNA damage increased in subjects possibly
      exposed to high amounts of antineoplastic agents. METHODS: The level of genetic
      damage was determined in peripheral mononuclear blood cells with the sister
      chromatid exchange test, the alkaline elution technique, and the cytokinesis
      block micronucleus test. RESULTS: The supposed increased exposure of the study
      subjects was caused by a malfunction of a safety hood resulting in leakage of air
      during preparation of an infusion of an antineoplastic drug. Two months after a
      new safety hood was installed, the frequencies of micronuclei and sister
      chromatid exchanges of exposed nurses (n = 10) were still significantly increased
      when compared with a matched control group (p < 0.01 and p < 0.05, one sided
      Wilcoxon test, respectively). In a second examination seven months later, the
      frequency of micronuclei had significantly decreased to control values (p < 0.05,
      one sided Wilcoxon test, n = 6). Moreover, the study subjects who smoked (n = 8)
      had significantly increased frequencies of micronuclei and sister chromatid
      exchanges (p < 0.01 and p < 0.05, one sided U test, respectively). No differences
      in the rate of DNA damage could be detected with the alkaline elution technique.
      CONCLUSIONS: Control measures on the level of biological effect should be
      performed regularly to ensure maximum safety precautions for workers potentially
      exposed to genotoxic agents.

PMID- 9624265
TI  - Chronic bronchitis, work related respiratory symptoms, and pulmonary function in
      welders in New Zealand.
AB  - OBJECTIVES: A cross sectional study of respiratory symptoms and lung function in
      welders was performed at eight New Zealand welding sites: 62 current welders and
      75 non-welders participated. METHODS: A questionnaire was administered to record
      demographic data, smoking habit, and current respiratory symptoms. Current and
      previous welding exposures were recorded to calculate a total lifetime welding
      fume exposure index. Forced expiratory volume in one second (FEV1), forced vital
      capacity (FVC), and peak expiratory flow (PEF) were measured before the start of
      the shift. RESULTS: There were no significant differences in ethnicity, smoking
      habits, or years of work experience between welders and non-welders. Symptoms of
      chronic bronchitis were more common in current welders (11.3%) than in non
      welders (5.0%). Of those workers with a cumulative exposure index to welding fume
      > or = 10 years, 16.7% reported symptoms of chronic bronchitis compared with 4.7%
      of those with a cumulative exposure index < 4 years (odds ratio (OR) 4.1, 95%
      confidence interval (95% CI) 0.90 to 17.6). Workers with chronic bronchitis had
      significantly lower measures of baseline PEF (p = 0.008) and FEV/FVC ratio (p =
      0.001) than workers without chronic bronchitis. Multivariate analysis showed that
      current smoking (OR 9.3, 1.0 to 86.9) and total exposure index to welding fumes >
      10 years (OR 9.5, 1.3 to 71.9) were independent risk factors for chronic
      bronchitis. The report of any work related respiratory symptom was more prevalent
      in welders (30.7%) than non-welders (15.0%) and workers with these symptoms had
      significantly lower FEV, (p = 0.004) and FVC (p = 0.04) values. Multivariate
      analysis identified a high proportion of time spent welding in confined spaces as
      the main risk factor for reporting these symptoms (OR 2.8, 1.0 to 8.3).
      CONCLUSION: This study has documented a high prevalence of symptoms of chronic
      bronchitis and other work related respiratory symptoms in current welders. Also,
      workers with chronic bronchitis had reduced PEF and FEV/FVC compared with those
      without chronic bronchitis. These symptoms related both to cigarette smoking and
      a measure of lifetime exposure to welding fume.

PMID- 9624266
TI  - Tyler asbestos workers: mortality experience in a cohort exposed to amosite.
AB  - OBJECTIVES: To examine the causes of death among 1130 former workers of a plant
      in Tyler, Texas dedicated to the manufacture of asbestos pipe insulation
      materials. This cohort is important and unusual because it used amosite as the
      only asbestiform mineral in the production process. High level exposure of such a
      specific type was documented through industrial hygiene surveys in the plant.
      METHODS: Deaths were ascertained through various sources including data tapes
      from the Texas Department of Health and the national death index files. As many
      death certificates as possible were secured (304/315) and cause of death
      assigned. After select exclusions, 222 death certificates were used in the
      analysis. Causes of death were compared with age, race, and sex specific
      mortalities for the United States population with a commercial software package
      (OCMAP Version 2.0). RESULTS: There was an excess of deaths from respiratory
      cancer including the bronchus, trachea, and lung (standardised mortality ratio
      (SMR) 277 with 95% confidence interval (95% CI) 193 to 385). Four pleural
      mesotheliomas and two peritoneal mesotheliomas were identified. The analysis also
      showed an increasing risk of respiratory malignancy with increased duration of
      exposure including a significant excess of total deaths from respiratory cancer
      with less than six months of work at the plant (SMR 268 with 95% CI 172 to 399).
      CONCLUSIONS: The importance of the cohort lies with the pure amosite exposure
      which took place in the plant and the extended period of latency which has
      followed. The death certificate analysis indicates the pathogenicity of amosite,
      the predominant commercial amphibole used in the United States. These data
      confirm a link between amosite asbestos and respiratory malignancy as well as
      mesothelioma.

PMID- 9624268
TI  - Epicondylitis among cooks in nursery schools.
AB  - OBJECTIVES: To investigate the prevalence and risk factors of epicondylitis among
      cooks in nursery schools in a cross sectional study because they are suspected to
      have strenuous workloads on the hands and arms. METHODS: Prevalence of
      epicondylitis among 209 nursery school cooks and 366 control workers aged 40-59
      were studied. Both groups consisted of women workers chosen from 1299 subjects
      who agreed to participate from 1329 social welfare employees in a city. All
      workers were interviewed with a questionnaire and had a clinical examination of
      the tenderness to palpation of epicondyles and epicondylar pain provoked by
      resisted extension and flexion of the wrist. RESULTS: Nursery school cooks had a
      significantly higher prevalence of epicondylitis (11.5%) than the controls
      (2.5%). In a logistic regression model, job title of the cook was also found to
      have a strong association with epicondylitis (odds ratio (OR) 5.4, 95% confidence
      interval (95% CI) 2.4 to 11.9) after adjustment for age, body length, and body
      mass index. Weaker associations were also found between epicondylitis and
      suspected job stress or workload scores for mechanical workload and psychosocial
      stressors based on factor analysis. CONCLUSIONS: This study supported the
      hypothesis that nursery school cooks had a higher prevalence of epicondylitis
      than other workers with less strenuous hand and arm tasks. It was suggested that
      risk factors of epicondylitis would be multifactorial, including mechanical
      workload and psychosocial factors.

PMID- 9624267
TI  - Mortality and cancer incidence of aircraft maintenance workers exposed to
      trichloroethylene and other organic solvents and chemicals: extended follow up.
AB  - OBJECTIVES: To extend the follow up of a cohort of 14,457 aircraft maintenance
      workers to the end of 1990 to evaluate cancer risks from potential exposure to
      trichloroethylene and other chemicals. METHODS: The cohort comprised civilians
      employed for at least one year between 1952 and 1956, of whom 5727 had died by 31
      December 1990. Analyses compared the mortality of the cohort with the general
      population of Utah and the mortality and cancer incidence of exposed workers with
      those unexposed to chemicals, while adjusting for age, sex and calendar time.
      RESULTS: In the combined follow up period (1952-90), mortality from all causes
      and all cancer was close to expected (standardised mortality ratios (SMRs) 97 and
      96, respectively). Significant excesses occurred for ischaemic heart disease (SMR
      108), asthma (SMR 160), and cancer of the bone (SMR 227), whereas significant
      deficits occurred for cerebrovascular disease (SMR 88), accidents (SMR 70), and
      cancer of the central nervous system (SMR 64). Workers exposed to
      trichloroethylene showed non-significant excesses for non-Hodgkin's lymphoma
      (relative risk (RR) 2.0), and cancers of the oesophagus (RR 5.6), colon (RR 1.4),
      primary liver (RR 1.7), breast (RR 1.8), cervix (RR 1.8), kidney (RR 1.6), and
      bone (RR 2.1). None of these cancers showed an exposure-response gradient and RRs
      among workers exposed to other chemicals but not trichloroethylene often had RRs
      as large as workers exposed to trichloroethylene. Workers exposed to solvents
      other than trichloroethylene had slightly increased mortality from asthma, non
      Hodgkin's lymphoma, multiple myeloma, and breast cancer. CONCLUSION: These
      findings do not strongly support a causal link with trichloroethylene because the
      associations were not significant, not clearly dose-related, and inconsistent
      between men and women. Because findings from experimental investigations and
      other epidemiological studies on solvents other than trichloroethylene provide
      some biological plausibility, the suggested links between these chemicals and non
      Hodgkin's lymphoma, multiple myeloma, and breast cancer found here deserve
      further attention. Although this extended follow up cannot rule out a connection
      between exposures to solvents and some diseases, it seems clear that these
      workers have not experienced a major increase in cancer mortality or cancer
      incidence.

PMID- 9624269
TI  - Carpal tunnel syndrome and work organisation in repetitive work: a cross
      sectional study in France. Study Group on Repetitive Work.
AB  - OBJECTIVES: To study the determinants of signs of carpal tunnel syndrome (CTS) in
      repetitive industrial work, with special attention to occupational constraints at
      group level and management practices of the companies. METHOD: A cross sectional
      study was conducted in three sectors: assembly line; clothing and shoe industry;
      food industry. A total of 1210 workers in repetitive work, from 53 different
      companies, was compared with a control group of 337 workers. Constraints at the
      workplace were partly self declared, and partly assessed by the occupational
      physicians in charge of the employees of the company. The definition of CTS was
      based on a standardised clinical examination. RESULTS: CTS was associated with
      repetitive work, especially packaging. It was more frequent among subjects who
      declared psychological and psychosomatic problems and those with a body mass
      index > or = 27. Dissatisfaction with work, lack of job control, short cycle
      time, and having to press repeatedly with the hand were associated with the
      syndrome. An odds ratio (OR) of 2.24 was found for "just in time" production.
      CONCLUSION: The results emphasise the complexity of the determinants of CTS, the
      role of psychosocial factors at work and the potentially negative effects of some
      practices of the companies aimed at enhancing their competitiveness.

PMID- 9624270
TI  - Epidemiology of sick building syndrome and its associated risk factors in
      Singapore.
AB  - OBJECTIVES: To investigate the occurrence of sick building syndrome in a tropical
      city, and its relation to indoor air quality and other factors. METHODS: 2856
      office workers in 56 randomly selected public and private sector buildings were
      surveyed. The study consisted of a self administered questionnaire assessing
      symptoms and perception of the physical and psychosocial environment, inspection
      of the building plans and premises, and measurement of temperature, relative
      humidity, respirable particles, chemicals, bioaerosols, and other variables.
      RESULTS: Symptoms typical of the sick building syndrome were reported in 19.6% of
      the respondents. Multivariate modelling substantiated contributions associated
      with low thermal comfort, high work related stress, too much noise, a history of
      allergy or other medical conditions, poor lighting, young employees, and female
      sex. Measurements of indoor air quality or ventilation were not found to be
      reliable predictors of the symptoms. CONCLUSION: The survey confirmed the
      presence of sick building syndrome and its risk factors in the tropics. A
      biopsychosocial approach to the problem involving symptomatic treatment,
      environmental control, good ergonomic design, and stress management is
      recommended.

PMID- 9624271
TI  - Use of a crop and job specific exposure matrix for retrospective assessment of
      long-term exposure in studies of chronic neurotoxic effects of agrichemicals.
AB  - RATIONALE: Job exposure matrices (JEMs) are widely used in occupational
      epidemiology, particularly when biological or environmental monitoring data are
      scanty. However, as with most exposure estimates, JEMs may be vulnerable to
      misclassification. OBJECTIVES: To estimate the long term exposure of farm workers
      based on a JEM developed for use in a study of the neurotoxic effects of
      organophosphates and to evaluate the repeatability and validity of the JEM.
      METHODS: A JEM was constructed with secondary data from industry and expert
      opinion of the estimate of agrichemical exposure within every possible job
      activity in the JEM to weight job days for exposure to organophosphates.
      Cumulative lifetime and average intensity exposure of organophosphate exposure
      were calculated for 163 pesticide applicators and 84 controls. Repeat
      questionnaires were given to 29 participants three months later to test
      repeatability of measurements. The ability of JEM based exposure to predict a
      known marker of organophosphate exposure was used to validate the JEM. RESULTS:
      Cumulative lifetime exposure as measured in kg organophosphate exposure, was
      significantly associated with erythrocyte cholinesterase concentrations (partial
      r2 = 5%; p < 0.01), controlled for a range of confounders. Repeatability in a
      subsample of 29 workers of the estimates of cumulative (Pearson's r = 0.67; 95%
      confidence interval (95% CI) 0.41 to 0.83), and average lifetime intensity of
      exposure (Pearson's r = 0.60 95% CI 0.31 to 0.79) was adequate. CONCLUSION: The
      JEM seems promising for farming settings, particularly in developing countries
      where data on chemical application and biological monitoring are unavailable.

PMID- 9624272
TI  - Occupational exposure to lead and neuropsychological dysfunction.
AB  - OBJECTIVE: To evaluate the neuropsychological effects of current low level and
      previous higher levels of exposure to lead and evaluate the relation between
      effects of lead and bone lead. METHODS: A neuropsychological test battery was
      given to 54 storage battery workers with well documented long term exposure to
      lead. The effect was studied in two subgroups: those whose blood lead had never
      exceeded 2.4 mmol/l (the low BPbmax group, n = 26), and those with higher
      exposure about 10 years earlier (the high BPbmax group, n = 28). In both groups,
      the recent exposure had been low. Correlations between the test scores and the
      indices of both long term and recent exposure--including the content of lead in
      the tibial and calcaneal bone--and covariance analyses were used to assess the
      exposure-effect relation. Age, sex, and education were controlled in these
      analyses. RESULTS: Analyses within the low BPbmax group showed a decrement in
      visuospatial and visuomotor function (block design, memory for design, Santa Ana
      dexterity), attention (digit symbol, digit span), and verbal comprehension
      (similarities) associated with exposure to lead and also an increased reporting
      of subjective symptoms. The performance of the high BPbmax group was worse than
      that of the low BPbmax group for digit symbol, memory for design, and embedded
      figures, but there was no reporting of symptoms related to exposure, probably due
      to selection in this group. No relation was found between the output variables
      and the tibial lead concentration. The calcaneal lead concentrations were related
      to the symptoms in the low BPbmax group. CONCLUSIONS: Neuropsychological
      decrements found in subjects with high past and low present exposure indicate
      that blood lead concentrations rising to 2.5-4.9 mmol/l cause a risk of long
      lasting or even permanent impairment of central nervous system function. Milder
      and narrower effects are associated with lower exposures; their reversibility and
      time course remain to be investigated. History of blood lead gives a more
      accurate prediction of the neuropsychological effects of lead than do
      measurements of bone lead.

PMID- 9624273
TI  - Role of human neurobehavioural tests in regulatory activity on chemicals.
AB  - Psychological performance tests have been used since the mid-1960s in
      occupational and environmental health toxicology. The interpretation of
      significantly different test scores in neurobehavioural studies is not
      straightforward in the regulation of chemicals. This paper sets out some issues
      which emerged from discussions at an international workshop, organised by the
      United Kingdom Health and Safety Executive (HSE), to discuss differences in
      interpretation of human neurobehavioural test data in regulatory risk
      assessments. The difficulties encountered by regulators confronted with
      neurobehavioural studies seem to be twofold; some studies lack scientific rigor;
      other studies, although scientifically sound, are problematic because it is not
      clear what interpretation to place on the results. Issues relating to each of
      these points are discussed. Next, scenarios within which to consider the outcomes
      of neurobehavioural studies are presented. Finally, conclusions and
      recommendations for further work are put forward.

PMID- 9624274
TI  - Occupational asthma in New Zealanders: a population based study.

PMID- 9624275
TI  - Work shift duration: a review comparing eight hour and 12 hour shift systems.
AB  - OBJECTIVES: Shiftwork is now a major feature of working life across a broad range
      of industries. The features of the shift systems operated can impact on the
      wellbeing, performance, and sleep of shiftworkers. This paper reviews the current
      state of knowledge on one major characteristic of shift rotas-namely, shift
      duration. Evidence comparing the relative effects of eight hour and 12 hour
      shifts on fatigue and job performance, safety, sleep, and physical and
      psychological health are considered. At the organisational level, factors such as
      the mode of system implementation, attitudes towards shift rotas, sickness
      absence and turnover, overtime, and moonlighting are discussed. METHODS: Manual
      and electronic searches of the shiftwork research literature were conducted to
      obtain information on comparisons between eight hour and 12 hour shifts. RESULTS:
      The research findings are largely equivocal. The bulk of the evidence suggests
      few differences between eight and 12 hour shifts in the way they affect people.
      There may even be advantages to 12 hour shifts in terms of lower stress levels,
      better physical and psychological wellbeing, improved durations and quality of
      off duty sleep as well as improvements in family relations. On the negative side,
      the main concerns are fatigue and safety. It is noted that a 12 hour shift does
      not equate with being active for only 12 hours. CONCLUSIONS: There can be
      considerable extension of the person's time awake either side of the shift.
      However, the effects of longer term exposure to extended work days have been
      relatively uncharted in any systematic way. Longitudinal comparative research
      into the chronic impact of the compressed working week is needed.

PMID- 9624276
TI  - Mortality from cancer and other causes of death among synthetic rubber workers.
AB  - OBJECTIVES: This study evaluated the mortality experience of workers from the
      styrene-butadiene rubber industry. Concerns about a possible association of 1,3
      butadiene and styrene with lymphohaematopoietic, gastrointestinal, and lung
      cancers prompted the investigation. METHODS: A retrospective follow up study was
      conducted of 15,649 men employed for at least one year at any of eight North
      American styrene-butadiene rubber plants. Analyses used standardised mortality
      ratios (SMRs) to compare styrene-butadiene rubber workers' cause specific
      mortalities (1943-91) with those of the United States and Ontario general
      populations. RESULTS: On average, there were 25 years of follow up per subject.
      The standardised mortality ratio (SMR) was 87 (95% confidence interval (95% CI)
      85 to 90) for all causes of death combined and was 93 (95% CI 87 to 99) for all
      cancers. There was an excess of leukaemia (SMR 131, 95% CI 97 to 174), restricted
      to hourly workers (SMR 143, 95% CI 104 to 191). For causes of death other than
      leukaemia, SMRs were close to or below the null value of 100. Results by work
      area (process group) were unremarkable for non-Hodgkin's lymphoma, multiple
      myeloma, and stomach cancer. Maintenance workers had a slight increase in deaths
      from lung cancer, and certain subgroups of workers had more than expected deaths
      from cancer of the large intestine and the larynx. CONCLUSION: This study found
      an excess of leukaemia that is likely to be due to exposure to butadiene or to
      butadiene plus other chemicals. Deaths from non-Hodgkin's lymphoma, multiple
      myeloma, and stomach cancer did not seem to be related to occupational exposure.
      The excess deaths from lung cancer among maintenance workers may be due in part
      to confounding by smoking, which was not controlled for, and in part to an
      unidentified occupational exposure other than butadiene or styrene. Increases in
      cancer of the large intestine and larynx were based on small numbers, did not
      seem to be due to exposure to butadiene or styrene, and may be chance
      observations.

PMID- 9624277
TI  - Lung cancer mortality in nickel/chromium platers, 1946-95.
AB  - OBJECTIVES: To investigate mortality from lung cancer in nickel/chromium platers.
      METHODS: The mortality experience of a cohort of 1762 chrome workers (812 men,
      950 women) from a large electroplating and light engineering plant in the
      Midlands, United Kingdom, was investigated for the period 1946-95. All subjects
      were first employed in chrome work at the plant during the period 1946-75, and
      had at least six months employment in jobs associated with exposure to chromic
      acid mist (hexavalent chromium). Detailed job histories were abstracted from
      original company personnel records and individual cumulative durations of
      employment in three types of chrome work were derived as time dependent variables
      (chrome bath work, other chrome work, any chrome work). Two analytical approaches
      were used--indirect standardisation and Poisson regression. RESULTS: Based on
      mortalities for the general population of England and Wales, male workers with
      some period of chrome bath work had higher lung cancer mortalities (observed
      deaths 40, expected deaths 25.41, standardised mortality ratio (SMR) 157, 95%
      confidence interval (95% CI) 113 to 214, p < 0.01) than did other male chrome
      workers (observed 9, expected 13.70, SMR 66, 95% CI 30 to 125). Similar findings
      were shown for female workers (chrome bath workers: observed 15, expected 8.57,
      SMR 175, 95% CI 98 to 289, p = 0.06; other chrome workers: observed 1, expected
      4.37, SMR 23, 95% CI 1 to 127). Poisson regression was used to investigate risks
      of lung cancer relative to four categories of cumulative duration of chrome bath
      work and four categories of cumulative duration of other chrome work (none, < 1
      y, 1-4 y, > or = 5 y). After adjusting for sex, age, calendar period, year of
      starting chrome work, period from first chrome work, and employment status (still
      employed v left employment), there was a significant positive trend (p < 0.05)
      between duration of chrome bath work and risks of mortality for lung cancer.
      Relative to a risk of unity for those chrome workers without any period of chrome
      bath work, risks were 2.83 (95% CI 1.47 to 5.45), 1.61 (95% CI 0.75 to 3.44), and
      4.25 (95% CI 1.83 to 9.87) for the second, third, and fourth exposure categories,
      respectively. Duration of other chrome work was not a useful predictor of risks
      of lung cancer. Similar findings for both variables were obtained when adjustment
      was made for sex and age only. Similar findings for both variables were obtained
      relative to risk of chrome nasal ulceration. CONCLUSIONS: The findings are
      consistent with the hypothesis that soluble hexavalent chromium compounds are
      potent human lung carcinogens.

PMID- 9624279
TI  - Evaluation of personal exposure to monoaromatic hydrocarbons.
AB  - OBJECTIVES: To evaluate the personal exposure of members of the general public to
      atmospheric benzene, toluene, and the xylenes, excluding exposure from active
      smoking. METHOD: 50 volunteers were equipped with active air samplers for direct
      measurement of personal exposure to monoaromatic hydrocarbons (MAH) and an
      activity diary was completed during each sampling period. Exposures were also
      estimated indirectly by combining activity data with independent measurements of
      hydrocarbon concentrations in several microenvironments. RESULTS: Personal
      exposure were generally well in excess of those which would be inferred from
      outdoor measurements from an urban background monitoring station. A wide range of
      sources contribute to exposure, with indoor and in car concentrations generally
      exceeding those measured at background outdoor locations. Environments
      contaminated with tobacco smoke were among those exhibiting the highest
      concentrations. Personal exposures determined indirectly from activity
      diaries/microenvironment measurements were well correlated with those determined
      directly with personal samplers. Personal 12 hour daytime exposures to benzene
      ranged from 0.23-88.6 ppb (mean 3.81 ppb), with 12 hour night time exposures of
      0.61-5.67 ppb (mean 1.94 ppb) compared with an annual average concentration of
      1.18 ppb at the nearest suburban fixed site monitoring station. The excess of
      personal exposure over fixed site concentrations was greater for benzene and
      toluene than for the xylenes. CONCLUSION: A wide range of sources contribute to
      personal exposures to monoaromatic hydrocarbons with exposure duration being as
      important a determinant of total exposure as concentrations. Exposures generally
      exceed those estimated from concentrations measured by background fixed point
      monitors. Microenvironment sampling combined with activity diary information can
      provide satisfactory estimates of personal exposure to these compounds.

PMID- 9624278
TI  - Silica, compensated silicosis, and lung cancer in Western Australian goldminers.
AB  - OBJECTIVES: Silica has recently been reclassified as carcinogenic to humans based
      largely on the observed increase in rates of lung cancer in subjects with
      silicosis. Other recent reviews have arrived at different conclusions as to
      whether silicosis or silica itself is carcinogenic. This study aims to examine
      exposure-response relations between exposure to silica and subsequent silicosis
      and lung cancer in a cohort of goldminers. METHODS: 2,297 goldminers from
      Kalgoorlie in Western Australia were examined in 1961, 1974, and 1975. Data were
      collected on respiratory symptoms, smoking habits, and employment history.
      Subjects were followed up to the end of 1993. Survival analyses for lung cancer
      mortality and incidence of compensated silicosis were performed with age and year
      matched conditional logistic regression analyses. RESULTS: 89% of the cohort were
      traced to the end of 1993. 84% of the men had smoked at some time and 66% were
      current smokers. 1386 deaths occurred during the follow up period, 138 from lung
      cancer, and 631 subjects were compensated for silicosis. A strong effect of
      smoking on mortality from lung cancer, and a smaller effect on the incidence of
      compensated silicosis was found. There was a strong effect of duration and
      intensity of exposure on the incidence of silicosis. The risk of mortality from
      lung cancer increased after compensation for silicosis. Of all direct measures of
      exposure to silica, only log cumulative exposure was significantly related to
      incidence of lung cancer, but this effect disappeared once the onset of silicosis
      was taken into account. CONCLUSIONS: The incidence of silicosis was clearly
      related to exposure to silica and the onset of silicosis conferred a significant
      increase in risk for subsequent lung cancer, but there was no evidence that
      exposure to silica caused lung cancer in the absence of silicosis.

PMID- 9624280
TI  - Respiratory symptoms and bronchial responsiveness in lifeguards exposed to
      nitrogen trichloride in indoor swimming pools.
AB  - OBJECTIVES: To measure the levels of exposure to nitrogen trichloride (NCl3) in
      the atmosphere of indoor swimming pools and to examine how they relate to
      irritant and chronic respiratory symptoms, indices of pulmonary function, and
      bronchial hyperresponsiveness to methacholine in lifeguards working in the pools.
      METHOD: 334 lifeguards (256 men; 78 women) recruited from 46 public swimming
      pools (n = 228) and 17 leisure centre swimming pools (n = 106) were examined.
      Concentrations of NCl3 were measured with area samplers. Symptoms were assessed
      by questionnaire and methacholine bronchial challenge (MBC) test by an
      abbreviated method. Subjects were labelled MBC+ if forced expiratory volume in
      one second (FEV1) fell by > or = 20%. The linear dose-response slope was
      calculated as the percentage fall in FEV1 at the last dose divided by the total
      dose given. RESULTS: 1262 samples were taken in the 63 pools. Mean NCl3
      concentrations were greater in leisure than in public pools. A significant
      concentration-response relation was found between irritant eye, nasal, and throat
      symptoms-but not chronic respiratory symptoms-and exposure concentrations. Among
      women, the prevalence of MBC+ was twice as great as in men. Overall, no relation
      was found between bronchial hyperresponsiveness and exposure. CONCLUSIONS: The
      data show that lifeguards exposed to NCl3 in indoor swimming pools are at risk of
      developing irritant eye, nasal, and throat symptoms. Exposure to NCl3 does not
      seem to carry the risk of developing permanent bronchial hyperresponsiveness, but
      this association might have been influenced by self selection. The possibility
      that subjects exposed to NCl3 are at risk of developing transient bronchial
      hyperresponsiveness cannot be confidently ruled out.

PMID- 9624281
TI  - Surveillance case definitions for work related upper limb pain syndromes.
AB  - OBJECTIVES: To establish consensus case definitions for several common work
      related upper limb pain syndromes for use in surveillance or studies of the
      aetiology of these conditions. METHODS: A group of healthcare professionals from
      the disciplines interested in the prevention and management of upper limb
      disorders were recruited for a Delphi exercise. A questionnaire was used to
      establish case definitions from the participants, followed by a consensus
      conference involving the core group of 29 people. The draft conclusions were
      recirculated for review. RESULTS: Consensus case definitions were agreed for
      carpal tunnel syndrome, tenosynovitis of the wrist, de Quervain's disease of the
      wrist, epicondylitis, shoulder capsulitis (frozen shoulder), and shoulder
      tendonitis. The consensus group also identified a condition defined as "non
      specific diffuse forearm pain" although this is essentially a diagnosis made by
      exclusion. The group did not have enough experience of the thoracic outlet
      syndrome to make recommendations. CONCLUSIONS: There was enough consensus between
      several health professionals from different disciplines to establish case
      definitions suitable for use in the studies of several work related upper limb
      pain syndromes. The use of these criteria should allow comparability between
      studies and centres and facilitate research in this field. The criteria may also
      be useful in surveillance programmes and as aids to case management.

PMID- 9624282
TI  - Prevalence odds ratio or prevalence ratio in the analysis of cross sectional
      data: what is to be done?
AB  - OBJECTIVES: To review the appropriateness of the prevalence odds ratio (POR) and
      the prevalence ratio (PR) as effect measures in the analysis of cross sectional
      data and to evaluate different models for the multivariate estimation of the PR.
      METHODS: A system of linear differential equations corresponding to a dynamic
      model of a cohort with a chronic disease was developed. At any point in time, a
      cross sectional analysis of the people then in the cohort provided a prevalence
      based measure of the effect of exposure on disease. This formed the basis for
      exploring the relations between the POR, the PR, and the incidence rate ratio
      (IRR). Examples illustrate relations for various IRRs, prevalences, and
      differential exodus rates. Multivariate point and interval estimation of the PR
      by logistic regression is illustrated and compared with the results from
      proportional hazards regression (PH) and generalised linear modelling (GLM).
      RESULTS: The POR is difficult to interpret without making restrictive assumptions
      and the POR and PR may lead to different conclusions with regard to confounding
      and effect modification. The PR is always conservative relative to the IRR and,
      if PR > 1, the POR is always > PR. In a fixed cohort and with an adverse
      exposure, the POR is always > or = IRR, but in a dynamic cohort with sufficient
      underlying follow up the POR may overestimate or underestimate the IRR, depending
      on the duration of follow up. Logistic regression models provide point and
      interval estimates of the PR (and POR) but may be intractable in the presence of
      many covariates. Proportional hazards and generalised linear models provide
      statistical methods directed specifically at the PR, but the interval estimation
      in the case of PH is conservative and the GLM procedure may require constrained
      estimation. CONCLUSIONS: The PR is conservative, consistent, and interpretable
      relative to the IRR and should be used in preference to the POR. Multivariate
      estimation of the PR should be executed by means of generalised linear models or,
      conservatively, by proportional hazards regression.

PMID- 9624283
TI  - Time to pregnancy and exposure to pesticides in Danish farmers. ASCLEPIOS Study
      Group.
AB  - OBJECTIVE: Circumstantial evidence suggests that organic farmers may have higher
      sperm count than other men, but comprehensive epidemiological studies of male
      fecundity among farmers have never been carried out. A substantial increase of
      sperm count is expected to translate into a shorter time to pregnancy--the number
      of menstrual cycles or months it takes a couple to get pregnant from
      discontinuation of birth control. Toxicological effects on spermatogenesis in
      humans and animals have been described after exposure to several pesticides. The
      aim of this study was to examine time to pregnancy among farmers who used
      pesticides (traditional farmers) and farmers who did not (organic farmers).
      METHODS: A total of 904 (84%) men, selected from the Danish Ministry of
      Agriculture lists of traditional and organic farmers, participated in telephone
      interviews. Information was collected on time to pregnancy for the youngest
      child, exposure to pesticides, and potential confounders. RESULTS: With the
      discrete analogue of the Cox regression model (including potential confounders:
      male and female smoking, female age, parity, and contraceptive method), the
      fecundability ratio between traditional farmers who used pesticides and organic
      farmers was 1.03 (95% confidence interval (95% CI) 0.75 to 1.40). In the group of
      farmers who sprayed with pesticides, none of the characteristics related to the
      use of pesticides could account for the variation in time to pregnancy.
      CONCLUSIONS: No overall effect of pesticides on male fecundability was found in
      this retrospective study among Danish farmers. Also, we found no evidence of
      higher male fecundability in organic farmers.

PMID- 9624284
TI  - Maternal occupation in the leather industry and selected congenital
      malformations.
AB  - OBJECTIVES: Data from a hospital based case-control study were analysed to assess
      the relation between maternal occupation in the leather industry and several
      groups of congenital defects (nervous system, cardiac defects of closure, oral
      cleft, epispadia or hypospadia, and multiple anomalies). METHODS: Cases and
      controls were selected from eight public hospitals in Comunidad Valenciana,
      Spain, in 1993 and 1994. Cases were located from the hospital discharge records,
      including children born and diagnosed in some of the selected hospitals during
      their first year of life. Controls were selected from births without congenital
      defects in the same hospitals and dates of the cases (ratio 1:1). Both parents of
      selected children were interviewed (mainly by phone) and information about
      potential confounding variables and occupational history during the three years
      before the birth was collected in structured questionnaires. RESULTS: A total of
      261 cases and the same number of controls were included in the study. Adjusted
      odds ratios (ORs) were estimated for maternal occupation in the leather industry
      in the period between three months before the conception and the birth of the
      child (n = 22), and each selected group of congenital malformations: nervous
      system defects (OR 1.02, 95% confidence interval (95% CI) 0.12 to 8.51), cardiac
      defects of closure (OR 1.78, 95% CI 0.44 to 7.17), oral clefts (OR 6.18, 95% CI
      1.48 to 25.69), for epispadia or hypospadia (OR 4.05, 95% CI 0.77 to 21.44), and
      multiple anomalies (OR 3.14, 95% CI 0.82 to 12.00). CONCLUSION: These data are
      compatible with an increased risk for oral clefts in the offspring of women
      working in the leather industry. Some other categories of defect could have an
      increased risk as well, although for these our data cannot exclude random error
      as an explanation. Given these results and previous findings in similar studies,
      some precautionary recommendations regarding maternal exposure in leather
      industries, probably in relation to solvents, would be justified.

PMID- 9624285
TI  - Respiratory health effects of opencast coalmining: a cross sectional study of
      current workers.

PMID- 9624286
TI  - Pulsed electromagnetic fields and cancer.

PMID- 9624287
TI  - Sputum induction to assess airway inflammation: is it an inflammatory stimulus?

PMID- 9624288
TI  - Is the lung important as a privileged site for the human immunodeficiency virus?

PMID- 9624289
TI  - Changes in sputum composition between two inductions performed on consecutive
      days.
AB  - BACKGROUND: Sputnum induction is a non-invasive method for obtaining cellular and
      biochemical material from the airways and appears to be particularly suited for
      repeated testing. However, it has not been clarified whether repeated inductions
      lead to a change in sputum composition. The aim of this study was to compare
      induced sputum results between two inductions performed 24 hours apart. METHODS:
      Ten subjects with mild asthma and 19 healthy subjects were included. Sputum was
      obtained during three consecutive 10 minute periods of hypertonic saline
      inhalation. Samples were analysed separately for the three inhalation periods.
      Corresponding pooled values were computed, taking into account total cell numbers
      of each inhalation period. RESULTS: In the three consecutive inhalation periods
      mean (SE) percentages of neutrophils increased from 29.2 (4.2)%, 22.0 (4.6)% and
      14.5 (2.9)% on day 1 to 43.1 (5.3)%, 34.8 (5.5)% and 25.7 (5.3)% on day 2 in
      healthy subjects and from 21.3 (4.3)%, 24.1 (5.9)% and 15.9 (3.7)% to 35.9
      (6.9)%, 30.7 (7.1)% and 31.8 (6.5)% in asthmatic subjects. This parallel shift
      corresponded to a mean (95% CI) increase in the pooled percentages of neutrophils
      of 17.4 (11.6) to 23.3)% in healthy and 14.6 (1.2 to 28.0)% in asthmatic
      subjects. In contrast to neutrophils, the percentage of macrophages decreased
      from day 1 to day 2, while eosinophil and lymphocyte percentages did not change
      significantly. CONCLUSION: These results suggest that the induction procedure
      itself causes a change in the composition of sputum detectable after 24 hours.
      This effect has to be taken into account when repeated sputum induction is
      performed.

PMID- 9624290
TI  - Effect of repeated sputum induction on cell counts in normal volunteers.
AB  - BACKGROUND: Sputum induction is becoming more commonly used to assess airway
      inflammation. Since it is a relatively non-invasive procedure it may be useful
      for repeated measurements over a short period of time. METHODS: To assess the
      repeatability of the method over a 24 hour period, eight healthy, non-smoking,
      non-atopic subjects (four men) of mean age 30 years underwent sputum induction,
      repeated at eight hours and 24 hours. Sputum was induced by inhalation of 3.5%
      saline. Absolute and differential counts of inflammatory cells were performed on
      the whole sputum after dilution in Hank's balanced salt solution containing 1%
      dithiothreitol to solubilise the mucus content of the samples. RESULTS: There was
      a significant rise in the percentage of neutrophils in the eight hour sample
      compared with the baseline (57%, range 25-94% at eight hours compared with 28%,
      range 19-60%: median difference 26%). The median baseline percentage of
      macrophages was 55% (range 26-69%) which fell to 38% (range 3-56%: median
      difference 22%) at eight hours and 19% (range 14-59%: median difference 25%) at
      24 hours. There was no significant change in the differential counts of
      eosinophils, lymphocytes or columnar epithelial cells, nor in any of the absolute
      cell counts, at any time point. CONCLUSIONS: Sputum induction may have limited
      utility in serial assessment of neutrophilic airway inflammation in normal
      subjects within a 24 hour period.

PMID- 9624292
TI  - Measurement of sniff nasal and diaphragm twitch mouth pressure in patients.
AB  - BACKGROUND: Inspiratory muscle weakness is a recognised cause of unexplained
      dyspnoea. It may be suggested by the finding of a low static inspiratory mouth
      pressure (MIP), but MIP is a difficult test to perform, with a wide normal range;
      a low MIP may also occur if the patient has not properly performed the manoeuvre.
      Further investigation conventionally requires balloon catheters to obtain
      oesophageal (Poes) and transdiaphragmatic pressure (Pdi) during sniffs or phrenic
      nerve stimulation. Two non-invasive tests of inspiratory muscle strength have
      recently been described--nasal pressure during a maximal sniff (Sn Pnas) and
      mouth pressure during magnetic stimulation of the phrenic nerves (Tw Pmo). The
      use of these two tests in combination might identify patients without inspiratory
      muscle weakness who are unable to produce a satisfactory MIP< therefore avoiding
      the need for investigation with balloon catheters. METHODS: Thirty consecutive
      patients with clinically suspected inspiratory muscle weakness and a low MIP
      underwent both conventional (Sn Poes and Tw Pdi) and non-invasive testing (Sn
      Pnas and Tw Pmo). Weakness was considered to be excluded by a Sn Poes of > or =
      80 cm H20 or a Tw Pdi of > or = 20 cm H20. The limit values used to test the
      hypothesis were Sn Pnas > or = 70 cm H20 or Tw Pmo > or = 12 cm H20. RESULTS:
      Inspiratory muscle weakness was excluded in 17 of the 30 patients. Fifteen of
      these would have been identified using Sn Pnas and Tw Pmo, with better results
      when the two tests were combined. The cut off values selected for Sn Pnas and Tw
      Pmo were shown by ROC plots to indicate normal strength conservatively, avoiding
      failure to detect mild degrees of weakness. No patient with global weakness was
      considered normal by Sn Pnas or Tw Pmo. CONCLUSIONS: In most patients with normal
      inspiratory strength and a low MIP, Tw Pmo and Sn Pnas used in combination can
      reliably exclude global inspiratory muscle weakness, reducing the number of
      patients who need testing with balloon catheters.

PMID- 9624291
TI  - Correlation between exhaled nitric oxide, sputum eosinophils, and methacholine
      responsiveness in patients with mild asthma.
AB  - BACKGROUND: Eosinophils in induced sputum and exhaled nitric oxide (NO) are
      currently used as non-invasive markers in the assessment of airway inflammation
      in asthma. As both sputum eosinophils (%) and exhaled NO are raised in asthmatic
      subjects not receiving inhaled steroids and decreased following corticosteroid
      therapy, a relationship between them is plausible. METHODS: Exhaled NO was
      measured by chemiluminescence analyser, sputum induction by 3.5% saline
      inhalation, and bronchial responsiveness was measured as PC20FEV1 methacholine in
      35 stable asthmatic patients using beta 2 agonist alone and the correlation
      between these non-invasive markers of airway inflammation was studied. RESULTS:
      There were significant correlations between exhaled NO and PC20 (r = -0.64),
      exhaled NO and sputum eosinophils (%) (r = 0.48), and also between sputum
      eosinophils (%) and PC20 (r = -0.40). CONCLUSION: The correlation between exhaled
      NO and PC20 suggests that exhaled NO or the mechanisms leading to its increase
      may contribute to airway hyperresponsiveness in asthma. Furthermore, the
      relationship between sputum eosinophils (%), exhaled NO, and PC20 highlight the
      potential use of eosinophils (%) in induced sputum and exhaled NO to monitor the
      severity of asthma.

PMID- 9624293
TI  - Asthma and airway hyperresponsiveness among Belgian conscripts, 1978-91.
AB  - BACKGROUND: Although there is convincing evidence that the prevalence of asthma
      among children has increased over the last three decades, it remains uncertain
      whether such an upward trend has occurred in adults. The aim of this study was to
      assess whether the prevalence of asthma has changed in young Belgian adults in
      recent years. METHODS: A retrospective analysis was conducted of available
      statistics from the Belgian Armed Forces for the period 1978-91 because
      conscripts who reported a history of past or current asthma at call-up
      examination underwent standardised assessment of non-specific airway
      responsiveness by military chest physicians. Exemption from military service due
      to asthma was strictly based on the objective evidence of airway
      hyperresponsiveness. RESULTS: A mean of 48,331 conscripts aged 17-31 years were
      examined annually from 1978 to 1991. The prevalence of reported asthma rose from
      2.4% in 1978 to 7.2% in 1991, while the proportion of asthmatics with airway
      hyperresponsiveness remained little changed at 48.4% in 1978 and 51.4% in 1991.
      CONCLUSIONS: The observed increase in prevalence of reported asthma was not
      accompanied by a decrease in the proportion of conscripts with objectively
      measured airway hyperresponsiveness. These observations provide supporting
      evidence that the increase in asthma symptoms was not simply due to reporting
      bias.

PMID- 9624294
TI  - Radiofrequency resection of bronchial tumours in combination with cryotherapy:
      evaluation of a new technique.
AB  - BACKGROUND: A number of treatments, including Nd-YAG laser therapy,
      brachytherapy, cryotherapy, electrocautery, and photodynamic therapy, can re-open
      the obstructed bronchial lumen in patients with inoperable obstructive bronchial
      tumours. None of these is considered to be a "gold standard". METHODS: The
      results of a retrospective study of 98 patients treated by radiofrequency tissue
      ablation and subsequent cryotherapy between January 1994 and June 1995 are
      reported. The patients were divided in two groups according to whether they were
      treated either after (group 1, n = 50) or before (group 2, n = 48) radiotherapy
      and/or chemotherapy. Bronchoscopic follow up was performed. The intervention was
      considered successful if the lumen was opened by > 80% and partially successful
      if it was opened by > 50%. RESULTS: In group 1 treatment was successful in 60%,
      partially successful in 32%, and unsuccessful in 8%. The median survival time was
      five months from the time of bronchoscopic surgery. In group 2 treatment was
      successful in 66%, partially successful in 21.5%, and unsuccessful in 12.5%, with
      a median survival time of 14 months from the time of bronchoscopic treatment.
      Forty patients (24 in group 1 and 16 in group 2) received a Dumon stent.
      CONCLUSIONS: Radiofrequency bronchoscopic surgery with cryotherapy appears to be
      a useful technique in the treatment of tracheobronchial obstruction.

PMID- 9624295
TI  - Effect of an inhaled glucocorticosteroid on mast cell and smooth muscle beta 2
      adrenergic tolerance in mild asthma.
AB  - BACKGROUND: Regular inhaled beta 2 agonist therapy is associated with loss of
      bronchoprotection to indirect bronchial provocation challenges such as allergen
      or adenosine monophosphate (AMP), while directly acting challenge is less
      affected, implying preferential mast cell tolerance. Glucocorticosteroids may
      reverse such beta 2 adrenoreceptor tolerance and upregulate mast cell beta 2
      adrenoceptor function. METHODS: The effect of single high dose
      glucocorticosteroids on terbutaline induced loss of bronchoprotection was studied
      in a placebo controlled, double blind, cross-over study. Fifteen asthmatic
      subjects who were not taking inhaled glucocorticosteroids underwent two 10-day
      treatment periods with terbutaline (500 micrograms four times daily via
      Turbohaler), each followed by a single dose of inhaled budesonide (800 micrograms
      via Turbohaler) or identical placebo. RESULTS: Regular treatment with terbutaline
      resulted in significant loss of bronchoprotection to AMP (mean difference (95%
      CI) -1.7 (-3.0 to 0.4) doubling dilutions) but not to methacholine (mean
      difference -0.1 (-1.0 to 0.8) doubling dilutions). Single high dose budesonide
      increased the protective effect of terbutaline more to AMP than to methacholine
      challenge (+0.76 (0.3) doubling dilutions compared with +0.13 (0.4) doubling
      dilutions, respectively). The mean (SE) difference between budesonide and placebo
      for methacholine challenge was 0.08 (0.14) whereas that for AMP was 0.075 (0.15);
      p = NS. The difference in PC20 was not statistically significant when compared
      with placebo for either challenge agent. CONCLUSIONS: Inhaled
      glucocorticosteroids in a single dose had no significant effect in restoring
      terbutaline induced loss of bronchoprotection, implying that mast cell beta 2
      adrenoceptor sensitivity is not restored by a single dose of an inhaled
      glucocorticosteroid in asthma.

PMID- 9624296
TI  - Secretory leukoprotease inhibitor: a native antimicrobial protein presenting a
      new therapeutic option?
AB  - Secretory leukoprotease inhibitor (SLPI) is a low molecular weight serine
      protease inhibitor found on various mucosal surfaces and has been ascribed an
      important role in maintaining the protease-anti-protease balance of the airways.
      Recent scientific evidence has suggested that SLPI may also have a broad spectrum
      antibiotic activity that includes antiretroviral, bactericidal, and antifungal
      activity. Given the unpropitious development of drug resistance to infectious
      micro-organisms in the human population, the need for therapeutic alternatives in
      the treatment of infectious diseases has become clear. SLPI may prove valuable in
      the prophylaxis and future treatment of infectious diseases, yet the clinical
      efficacy of SLPI remains largely to be elucidated.

PMID- 9624297
TI  - Health effects of passive smoking .5. Parental smoking and allergic sensitisation
      in children.
AB  - BACKGROUND: A systematic review was conducted of the effects of parental smoking
      on immunoglobulin (IgE) levels, skin prick positivity, and allergic rhinitis or
      eczema in children. Asthma was excluded in order to distinguish more clearly the
      effect of passive smoke exposure on allergic sensitisation. METHODS: Thirty six
      relevant publications were identified after consideration of 692 articles
      selected by electronic search of the Embase and Medline databases using keywords
      relevant to passive smoking in children. The search was completed in April 1997
      and identified nine studies of IgE in neonates, eight of IgE in older children,
      12 which included skin prick tests, and 10 describing symptoms of allergic
      disease other than asthma or wheezing. A quantitative meta-analysis was possible
      only for the studies reporting skin prick tests. RESULTS: Several large studies
      failed to confirm early reports of a substantial or statistically significant
      association of maternal smoking with concentrations of total serum IgE in
      neonates or in older children. No consistent association emerged between parental
      smoking and allergic rhinitis or eczema. Few of these studies adjusted for
      potential confounding variables. The quantity and quality of evidence was
      greatest for skin prick tests, and studies of parental smoking during pregnancy
      or infancy were broadly consistent in showing no adverse effect on prick
      positivity (pooled odds ratio 0.87, 95% confidence interval 0.62 to 1.24). There
      was much greater and statistically significant (p = 0.002) heterogeneity of odds
      ratios relating current parental smoking to skin prick positivity. CONCLUSIONS:
      Parental smoking, either before or immediately after birth, is unlikely to
      increase the risk of allergic sensitisation in children.

PMID- 9624298
TI  - Lung infections. 2. Branhamella catarrhalis: epidemiological and clinical aspects
      of a human respiratory tract pathogen.

PMID- 9624299
TI  - Structural and inflammatory changes in COPD: a comparison with asthma.

PMID- 9624301
TI  - Opitz oculo-genito-laryngeal syndrome: a rare cause of recurrent aspiration
      pneumonia in an adult.
AB  - A 64 year old woman presented with persistent and severe symptoms due to
      recurrent aspiration pneumonias associated with oesophageal reflux. She had had
      multiple miscarriages and her son at birth had widely spaced eyes
      (hypertelorism), hypospadias, bilateral undescended testes, and an imperforate
      anus. Her daughter has mild hypertelorism and her daughter's son had neonatal
      inspiratory stridor, hypospadias and hypertelorism, all features now recognised
      as typical of the Opitz oculo-genito-laryngeal syndrome. This syndrome is
      genetically heterogeneous with autosomal dominant (linked to chromosome 22q21)
      and X-linked (linked to Xp22) inheritance. This family's history and genetic
      linkage data are consistent with linkage to Xp22. The proband is a manifesting
      carrier of this syndrome; her history of recurrent aspiration is probably
      secondary to pharyngeal neuromuscular incoordination aggravating gastro
      oesophageal reflux. Obtaining a family history gives a vital clue to the
      diagnosis of Opitz oculo-genito-laryngeal syndrome. It is also suggested that
      this condition should be included in the differential diagnosis of recurrent
      aspiration pneumonia.

PMID- 9624302
TI  - Familial primary spontaneous pneumothorax consistent with true autosomal dominant
      inheritance.
AB  - A family exhibiting spontaneous pneumothorax in a father and three offspring (two
      sons, and one daughter) is described. The mode of inheritance is apparently
      autosomal dominant with two episodes of male to male transmission in one family.
      The age of onset varied by up to 13 years within the family. Isolated autosomal
      dominant pneumothorax appears to be a distinct clinical entity.

PMID- 9624300
TI  - New therapies for chronic obstructive pulmonary disease.

PMID- 9624303
TI  - Can reactive airways dysfunction syndrome (RADS) transform into occupational
      asthma due to "sensitisation" to isocyanates?
AB  - The case history is described of a worker who presented with a history suggestive
      of reactive airways dysfunction syndrome which occurred after an acute high level
      inhalation of diphenylmethane diisocyanate. Further exposure at work, at a time
      when concentrations of isocyanates were no longer "irritant", suggested
      occupational asthma; this diagnosis was confirmed by a specific inhalation
      challenge test.

PMID- 9624304
TI  - Atopy phenotype.

PMID- 9624305
TI  - Lung volume reduction surgery.

PMID- 9624306
TI  - Predictors of occult pneumococcal bacteremia in young febrile children.
AB  - STUDY OBJECTIVE: Occult pneumococcal bacteremia (OPB) occurs in 2.5% to 3% of
      highly febrile children 3 to 36 months of age, and 10% to 25% of untreated
      patients with OPB experience complications, including 3% to 6% in whom meningitis
      develops. The purpose of this study was to identify predictors of OPB among a
      large cohort of young, febrile children treated as outpatients using
      multivariable statistical methods. METHODS: We derived and validated a logistic
      regression model for the prediction of OPB. We evaluated 6,579 outpatients 3 to
      36 months of age with temperatures of 39 degrees C or higher who previously had
      been enrolled in a study of young febrile patients at risk of OPB in the
      emergency departments of 10 hospitals in the United States between 1987 and 1991;
      164 patients (2.5%) had OPB. We randomly selected two thirds of this population
      for the derivation of the model and one third for validation. In the derivation
      set, we analyzed the univariate relationships of six variables with OPB: age,
      temperature, clinical score, WBC count, absolute neutrophil count (ANC), and
      absolute band count (ABC). All six variables were then entered into a logistic
      regression equation and those retaining statistical significance were considered
      to have an independent association with OPB. RESULTS: Patients with OPB were
      younger, more frequently ill-appearing, and had higher temperatures, WBC, ANC,
      and ABC than patients without bacteremia. Only three variables, however, retained
      statistically significant associations with OPB in the multivariate analysis: ANC
      (Adjusted odds ratio [OR] 1.15 for each 1,000 cells/mm3 increase, 95% confidence
      interval [CI] 1.06, 1.25), temperature (adjusted OR 1.77 for each 1 degree C
      increase, 95% CI 1.21, 2.58), and age younger than 2 years (adjusted OR 2.43
      versus patients 2 to 3 years old, 95% CI interval 1.11, 5.34). In the derivation
      set, 8.1% of patients with ANCs greater than or equal to 10,000 cell/mm3 had OPB
      (95% CI 6.3, 10.1%) versus .8% of patients with ANCs less than 10,000 cells/mm3
      (95% CI .5, 1.2%). When tested on the validation set, the model performed
      similarly. CONCLUSION: Independent predictors of OPB in children 3 to 36 months
      of age with temperatures of 39 degrees C or higher treated as outpatients include
      ANC, temperature, and age younger than 2 years. These predictors may be used to
      develop clinical strategies to limit laboratory testing and antibiotic
      administration to those children at greatest risk of OPB.

PMID- 9624307
TI  - Intramuscular ketamine for pediatric sedation in the emergency department: safety
      profile in 1,022 cases.
AB  - STUDY OBJECTIVE: To determine the safety of intramuscular ketamine when
      administered by emergency physicians for pediatric procedures in accordance with
      a defined protocol. METHODS: We assembled a consecutive case series of children
      aged 15 years or younger who were given ketamine in the emergency departments of
      a university medical center and an affiliated county hospital over a 9-year
      period. A protocol for ketamine use (4 mg/kg, intramuscularly) was followed.
      Treating physicians were instructed to complete data forms recording
      complications and adequacy of sedation concurrent with patient care. Subsequent
      chart review was used to determine indications, adjunctive drugs, time to
      discharge, and adverse reactions for all patients. RESULTS: Intramuscular
      ketamine was administered 1,022 times, mainly for laceration repair and fracture
      reduction. Physicians completed data forms for 431 of treated children (42%).
      Transient airway complications occurred in 1.4%: airway malalignment (n = 7),
      laryngospasm (n = 4), apnea (n = 2), and respiratory depression (n = 1). All were
      quickly identified and treated without intubation or sequelae. Emesis occurred in
      6.7%, without evidence of aspiration. Mild recovery agitation occurred in 17.6%,
      moderate to severe agitation in 1.6%. No child required hospitalization for
      complications caused by ketamine. Ketamine produced acceptable sedation in 98% of
      patients. The median time from injection to emergency department discharge was
      110 minutes for children given a single dose of ketamine. CONCLUSION:
      Intramuscular ketamine may be administered safely by emergency physicians to
      facilitate pediatric procedures in accordance with a defined protocol and with
      appropriate monitoring. Ketamine is highly effective, has a wide margin of
      safety, does not require intravenous access, and uniquely preserves protective
      airway reflexes.

PMID- 9624308
TI  - Does exogenous melatonin improve day sleep or night alertness in emergency
      physicians working night shifts?
AB  - STUDY OBJECTIVE: To determine whether exogenous melatonin improves day sleep or
      night alertness in emergency physicians working night shifts. METHODS: In a
      double-blind, placebo-controlled crossover trial, emergency physicians were given
      10 mg sublingual melatonin or placebo each morning during one string of nights
      and the other substance during another string of nights of equal duration. During
      day-sleep periods, subjective sleep data were recorded. During night shifts,
      alertness was assessed with the use of the Stanford Sleepiness Scale. Key outcome
      comparisons were visual analog scale scores for gestalt night alertness and for
      gestalt day sleep for the entire string of nights. RESULTS: We analyzed data from
      18 subjects. Melatonin improved gestalt day sleep (P = .3) and gestalt night
      alertness (P = .03) but in neither case was the improvement statistically
      significant. Of 13 secondary comparisons, 9 showed a benefit of melatonin over
      placebo; none showed a benefit of placebo over melatonin. CONCLUSION: Exogenous
      melatonin may be of modest benefit to emergency physicians working night shifts.

PMID- 9624309
TI  - Resource-use analysis of a medical toxicology consultation service.
AB  - STUDY OBJECTIVE: To evaluate the impact of a medical toxicology consulting
      service (MTCS) on resource use and efficiency of care in patients hospitalized
      with a diagnosis of tricyclic antidepressant (TCA) poisoning. METHODS: We
      conducted a retrospective, case-controlled medical-records review at two urban
      tertiary care teaching hospitals. The study population comprised patients who
      presented to the emergency department with a diagnosis of TCA poisoning, in two
      phases. The first phase was longitudinal; we evaluated cases over 4 years before
      and after inception of an MTCS at one institution. In the second phase we
      compared consecutive cases of TCA poisoning treated at two urban teaching
      hospitals located within a mile of each other with similar patient populations,
      one with and one without MTCS backup. Inclusion criteria consisted of complete
      medical records, ingestion of first- and second-generation TCAs, and age greater
      than 16 years. Patients were excluded if history, physical examination, or
      laboratory analysis suggested that multiple substances had been ingested.
      Extensive demographic data were collected in each case. Clinical information
      obtained from each patient included admission vital signs, pupil size, QRS and
      corrected QT duration, and the presence of markers of severe TCA toxicity such as
      hypotension, seizures, pulmonary edema, respiratory insufficiency necessitating
      intubation, and the occurrence of antimuscarinic signs and symptoms. Information
      regarding treatment was also collected from each case, including laboratory
      tests, decontamination procedures, administration of sodium bicarbonate, and use
      of other medications and therapies. RESULTS: We identified a total of 88 patients
      in both phases of the study. Comparison groups were similar with respect to age,
      sex, presenting vital signs, presenting QRS and corrected QT duration, and
      incidence of recorded antimuscarinic signs, hypotension, seizures, and
      respiratory insufficiency requiring intubation. Total length of stay in a
      monitored hospital bed was also similar between groups. One fatality was
      recorded, but all other patients were discharged home or to a psychiatric
      facility. Patients seen by the MTCS consumed fewer health care resources in the
      form of less decontamination and fewer laboratory tests. CONCLUSION: The MTCS may
      provide a resource-efficient means of treating patients with TCA poisoning. A
      larger, multicenter study of a variety of poisoned patients should be undertaken
      to further investigate this issue.

PMID- 9624310
TI  - Management of anaphylactoid reactions to intravenous N-acetylcysteine.
AB  - STUDY OBJECTIVE: To develop management guidelines for the treatment of
      anaphylactoid reactions to intravenous N-acetylcysteine (NAC) and to assess the
      safety of restarting the infusion after a reaction. METHODS: In phased 1, we used
      a 6-year retrospective case series of hospitalized patients and a review of the
      literature to develop the management guidelines for anaphylactoid reactions to
      intravenous NAC. In phase 2, these guidelines were evaluated prospectively in our
      poison-control center. RESULTS: In phase 1, the charts of 11 patients with
      anaphylactoid reactions (9 cutaneous and 2 systemic) were reviewed. In most
      cases, no treatment or treatment with diphenhydramine alone or with salbutamol
      was sufficient to continue or restart NAC infusion safely. On the basis of our
      findings in those patients and on published experience, we concluded that
      anaphylactoid reactions to intravenous NAC are dose-related and the
      antihistamines are useful in controlling and in preventing recurrence of
      anaphylactoid symptoms. We developed the following guidelines: flushing requires
      no treatment, urticaria should be treated with diphenhydramine, and NAC infusion
      should be continued in both cases. Angioedema and respiratory symptoms each
      require the administration of diphenhydramine and symptomatic therapy. In these
      cases, NAC infusion should be stopped but, when necessary, can be started 1 hour
      after the administration of diphenhydramine in the absence of symptoms. In phase
      2, 50 patients (31 cutaneous and 19 systemic reactions) were treated
      prospectively with the use of these guidelines. Recurrence of symptoms occurred
      in only one case involving a deviation from the guidelines. The NAC infusion was
      restarted immediately after the administration of diphenhydramine in a patient
      who sustained a systemic reaction. CONCLUSION: Non-life-threatening anaphylactoid
      reactions to intravenous NAC are treated easily and the infusion may be continued
      or restarted safely after the administration of diphenhydramine.

PMID- 9624311
TI  - Clinical course of gamma-hydroxybutyrate overdose.
AB  - STUDY OBJECTIVE: To describe the clinical characteristics and course of gamma
      hydroxybutyrate (GHB) overdose. METHODS: We assembled a retrospective series of
      all cases of GHB ingestion see in an urban public-hospital emergency department
      and entered in a computerized database January 1993 through December 1996. From
      these cases we extracted demographic information, concurrent drug use, vital
      signs, Glasgow Coma Scale (GCS) score, laboratory values, and clinical course.
      RESULTS: Sixty-one (69%) of the 88 patients were male. The mean age was 28 years.
      Thirty-four cases (39%) involved coingestion of ethanol, and 25 (28%) involved
      coingestion of another drug, most commonly amphetamines. Twenty-five cases (28%)
      had a GCS score of 3, and 28 (33%) had scores ranging from 4 through 8. The mean
      time to regained consciousness from initial presentation among nonintubated
      patients with an initial GCS of 13 or less was 146 minutes (range, 16-389).
      Twenty-two patients (31%) had an initial temperature of 35 degrees C or less.
      Thirty-two (36%) had asymptomatic bradycardia; in 29 of these cases, the initial
      GCS score was 8 or less. Ten patients (11%) presented with hypotension (systolic
      blood pressure < or = 90 mm Hg); 6 of these patients also demonstrated concurrent
      bradycardia. Arterial blood gases were measured in 30 patients; 21 had a PCO2 of
      45 or greater, with pH ranging from 7.24 to 7.34, consistent with mild acute
      respiratory acidosis. Twenty-six patients (30%) had an episode of emesis; in 22
      of these cases, the initial GCS was 8 or less. CONCLUSION: In our study
      population, patients who overdosed on GHB presented with a markedly decreased
      level of consciousness. Coingestion of ethanol or other drugs is common, as are
      bradycardia, hypothermia, respiratory acidosis, and emesis. Hypotension occurs
      occasionally. Patients typically regain consciousness spontaneously within 5
      hours of the ingestion.

PMID- 9624312
TI  - A tale of novel intoxication: seven cases of gamma-hydroxybutyric acid overdose.
AB  - STUDY OBJECTIVE: We describe seven patients presenting with combination substance
      abuse involving gamma-hydroxybutyric acid (GHB). METHODS: During a 3 month
      period, we identified consecutive patients with GHB ingestion confirmed by urine
      mass spectrometry presenting to a high-volume urban emergency department.
      RESULTS: All patients presented with acute delirium and transient but severe
      respiratory depression. With supportive care, including intubation and mechanical
      ventilation in four cases, normal mentation and respiratory function returned
      within 2 to 6 hours. None of these patients had documented seizures, and none of
      the four patients who received naloxone had a reversal response. This clinical
      observation supports previous experimental work in GHB-intoxicated human subjects
      demonstrating neither epileptiform changes on electroencephalography nor reversal
      with naloxone. Two findings are remarkable in this series. The first is the
      observation of a peculiar state of violent aggression present on stimulation of
      the GHB-intoxicated patient despite near or total apnea. The fact that patients
      fully recovered from this state may be the result of a previously demonstrated
      GHB hypoxia-sparing effect. The second is the observation of ECG abnormalities in
      several cases, including U waves in five patients. CONCLUSION: Emergency
      physicians should be alerted to this agent, its characteristic effects, and its
      potential for serious sequelae including respiratory arrest and death.

PMID- 9624313
TI  - A tale of novel intoxication: a review of the effects of gamma-hydroxybutyric
      acid with recommendations for management.
AB  - gamma-Hydroxybutyric acid (GHB) is unfamiliar to many physicians in the United
      States but enjoys clinical use elsewhere for applications in resuscitation,
      anesthesia, and addiction therapy. Use within the United States is restricted to
      Food and Drug Administration-approved clinical trials for treatment of
      narcolepsy. Recently illicit use of GHB has emerged within the United States
      where it is distributed for purported euphoric and "fat-burning" metabolic
      effects. Clinical effects can be severe, progressing rapidly to respiratory
      arrest and death. We provide an updated comprehensive review of the literature
      with particular emphasis on toxicology, including GHB pharmacodynamics, clinical
      effects, and suggestions for overdose management. Recommended management of acute
      GHB intoxication includes prevention of aspiration, use of atropine for
      persistent symptomatic bradycardia, consideration of neostigmine as a reversal
      agent, and treatment for coingested substances. Emergency physicians are urged to
      become familiar with GHB because of its potential for severe morbidity as well as
      its potential use as a future resuscitative agent.

PMID- 9624314
TI  - Night of the sirens: analysis of carbon monoxide-detector experience in suburban
      Chicago.
AB  - STUDY OBJECTIVE: To determine the pattern and environmental causes of carbon
      monoxide (CO)-detector alarms. METHODS: Data including time, location, detector
      manufacturer, CO measurements in the home, reported illness, cause, and actions
      taken were collected between July 15, 1994, and January 26, 1995, on all calls to
      17 suburban Chicago fire departments for CO-detector alarms. We used univariate
      time-series analysis involving joint estimation of model parameters and outlier
      effects to analyze data and compared data on ambient CO levels from the Illinois
      Environmental Protection Agency to the number of calls per day. RESULTS: During
      the study period, 777 calls for sounding CO detectors were made to the fire
      departments in question. The median number of calls per day was three. Our
      univariate time series identified 3 days with a significant excess of calls
      (December 12, 29 calls; December 21, 69; December 22, 128; P < .001). The average
      ambient CO readings on these days were 0.99, 3.25, and 3.89 ppm, respectively,
      compared with an overall mean of 8.8 ppm. In-home CO levels among all 828
      measurements taken from the 777 domestic calls ranged from 0 to 425 ppm, 0 in 249
      (30%), 1 to 10 in 340 (41%), 11 to 50 in 149 (18%), 51 to 100 in 22 (9%), and
      more than 100 in 11 (1.3%). No measurement was taken in six cases. Cause of alarm
      was listed as furnace in 25 cases, auto exhaust in 24, stove/oven in 22, poor
      location of detector in 14, water heater in 11, outside sources in 7, and
      multiple sources in 7. Other sources accounted for fewer than 1% each. The
      participating fire departments considered 242 cases (31%) to be false alarms.
      Cause was not determined in 400 calls (51%). In 37 calls (4.8%), people reported
      illness. CONCLUSION: Above-average ambient CO levels coincided with a significant
      increase in the number of calls and may have contributed to the triggering of CO
      alarms.

PMID- 9624315
TI  - Effect of a large managed care program on emergency department use: results from
      the CHAMPUS reform initiative evaluation.
AB  - STUDY OBJECTIVE: To determine the effect of the CHAMPUS Reform Initiative (CRI)
      on emergency department use and charges, and to ascertain whether any reductions
      were concentrated among repeat users of the ED, those with less serious ED
      diagnoses, or those with selected chronic medical conditions. METHODS:
      Participants were approximately 1.2 million beneficiaries of the Civilian Health
      and Medical Program of Uniformed Services (CHAMPUS) residing within either 11
      military hospital catchment areas in California and Hawaii ("demonstration
      areas") or 11 matched control areas in other parts of the United States. Under
      CRI, participants were offered a choice of the standard CHAMPUS indemnity plan, a
      Preferred Provider Organization-type plan, or a network-model Health Maintenance
      Organization plan. Beneficiaries were encouraged to use alternatives to the ED
      for nonemergency conditions. Visits to civilian EDs during two 12-month periods,
      before and after institution of CRI, were compared. RESULTS: Under CRI, the
      number of CHAMPUS ED visits decreased by approximately 40% relative to the
      control, and allowed charges fell by almost 50%. Relative reductions in ED use
      under CRI were seen among both frequent and infrequent users of the ED. ED case
      mix severity increased modestly relative to control (+3.5% versus +.9%). ED use
      among patients with diabetes, hypertension, and asthma fell sharply in the
      demonstration areas (by 14% to 41%) but rose in control areas (by 4% to 9%).
      CONCLUSION: In one of the largest managed care demonstrations ever conducted, a
      nonintrusive use management program and improved access to outpatient care
      appeared to reduce ED use, allowed charges, and costs to the government.
      Reductions in ED use were concentrated to some extent among repeat users and
      patients with less severe illnesses and were effected without capitation of
      provider groups or strict gatekeeping requirements.

PMID- 9624316
TI  - Emergency department use by nursing home residents.
AB  - STUDY OBJECTIVE: To describe a community's experience with the use of emergency
      department services by nursing home residents. METHODS: We performed a
      retrospective chart review of a population-based cohort of nursing home residents
      in an urban county in central Georgia with 10 nursing homes (1,300 beds) and 4
      hospital-based EDs. All ED visits by nursing home residents during 1995 were
      analyzed. Demographic data, timing of the visit, chief complaint, tests and
      treatments, disposition, and financial charges were recorded. Further, we
      calculated the number of ED visits per 100 nursing home patient-years. RESULTS: A
      total of 873 nursing home residents made 1,488 ED visits. Mean age was 76.0
      years; 66.4% were female, and 55.2% were white. Of the transfers, 42.9% occurred
      during regular working hours. The most common chief complaints were respiratory
      symptoms (14.4%), altered mental status (10.1%), gastrointestinal symptoms
      (9.9%), and falls (8.2%); 101 patients (6.8%) were transferred for malfunction of
      a gastrostomy tube. The most common laboratory tests were complete blood cell
      count (69.5%), chest radiograph (52.0%), electrocardiogram (45.0%), urinalysis
      (42.7%), and determination of electrolytes (42.7%). A total of 42.4% of the ED
      visits led to admission to the hospital. From the 10 nursing homes, there were
      110 ED visits per 100 patient-years. A 3.5-fold difference in ED use among these
      nursing homes could not be explained by age, gender, or other factors. The
      average .charge per ED visit was $1,239. CONCLUSION: Elders living in nursing
      homes are frequently transferred to EDs for costly medical evaluations, and more
      than 40% of such visits lead to admission to the hospital.

PMID- 9624317
TI  - Death in the emergency department.
AB  - Issues regarding the deaths of patients in the ED arise on a regular basis for
      emergency physicians. These issues include physician discomfort with death
      notification, the approach to families after ED deaths, autopsies, donation of
      organs and tissues, and procedures on the newly dead. If physicians were more
      comfortable with death notification, not only would families be better served but
      benefits to society could be realized through the increased use of autopsy and
      organ/tissue donation. The controversial topic of physician education through
      practice of medical procedures on the newly dead weighs the benefits to society
      against the rights of the individual. Improved physician education, including the
      need for a death notification plan and enlistment of the support of nursing
      personnel, social workers, and clergy, may improve the experience of events
      surrounding ED deaths for physicians, families, and society. We review the
      literature and give recommendations on approaches to deal with these issues.

PMID- 9624318
TI  - Emergency medicine in Madagascar.
AB  - The Democratic Republic of Madagascar lies off the southeastern coast of Africa
      and ranks as the fourth largest island in the world. Average per capita yearly
      income is about $400 (US). In 1990 life expectancies at birth were 52 years for
      men and 55 years for women. Graduate medical education in Madagascar is modeled
      after the French system.

PMID- 9624319
TI  - Diagnosis of intestinal injuries by computed tomography and the use of oral
      contrast medium.

PMID- 9624320
TI  - When does hypoglycemia develop after sulfonylurea ingestion?

PMID- 9624321
TI  - Delayed hypoglycemia in a child after ingestion of a single glipizide tablet.
AB  - This is the first report to describe the delayed onset of hypoglycemia in a child
      after ingestion of one tablet of glipizide. A 2-year-old boy was observed to
      ingest 5 mg glipizide and 25 mg hydrochlorothiazide. Activated charcoal was
      administered within 35 minutes of ingestion. Hypoglycemia (serum glucose 49
      mg/dL) developed 11 hours later. Emergency physicians must be aware of the
      potential for delayed hypoglycemia in children with single-tablet ingestions of
      glipizide. Prolonged monitoring of glucose levels is warranted.

PMID- 9624322
TI  - Electromechanical dissociation 48 hours after atenolol overdose: usefulness of
      calcium chloride.
AB  - Electromechanical dissociation (EMD) occurred in a 20-year-old woman 48 hours
      after an overdose of atenolol, despite intensive treatment of the beta-blocker
      poisoning (gastric lavage, charcoal, glucagon, epinephrine, atropine, correction
      of electrolyte abnormalities, administration of fluids, cardiac pacing, and
      mechanical ventilation). Administration of calcium chloride during EMD repeatedly
      restored blood pressure. Therefore it may have a role to play in management of
      atenolol overdose.

PMID- 9624323
TI  - National conference on medical indication for air bag disconnection--July 16-18,
      1997. National Highway Traffic Safety Administration.

PMID- 9624324
TI  - Commentary: air bags--the changing landscape.

PMID- 9624325
TI  - Change of shift.

PMID- 9624326
TI  - Cinderella's road map.

PMID- 9624327
TI  - Telemedicine revisited.

PMID- 9624328
TI  - Premixed charcoal, iron, and deferoxamine.

PMID- 9624329
TI  - t-PA in acute ischemic stroke.

PMID- 9624330
TI  - Oil of wintergreen overdose.

PMID- 9624331
TI  - "DXM": a new drug of abuse?

PMID- 9624332
TI  - Ender nailing of acute humeral shaft fractures in multiple injuries.
AB  - From January 1987 to April 1993, 25 multiply injured patients were treated with
      closed intramedullary Ender nail fixation of the humeral shaft. Criteria for the
      procedure were humeral diaphyseal fractures with associated multiple injuries.
      Seventeen distal and mid-shaft fractures were treated via a modified anterograde
      approach in which the rotator cuff is not violated. Eight proximal third
      fractures were treated via the standard retrograde approach. Postoperative follow
      up averaged 36 months. Full range of motion was attained 17 of the 25 patients.
      Of the eight remaining patients, three with a slightly limited range of motion
      achieved full range of motion following nail removal; three had preoperative
      radial nerve palsy which resolved within 1 year, and two patients required follow
      on plating. In 92 per cent (23 of 25) there were no incidences of infection or
      non-union. Flexible nails avoid complications of reaming. The modified
      anterograde approach allows excellent shoulder motion since it does not violate
      the rotator cuff. Ender nails provide excellent fixation and clinical outcome in
      the multiply injured patient and are cost effective compared with interlocking
      nails.

PMID- 9624333
TI  - Primary free-flap cover of open tibial fractures.
AB  - Seventeen consecutive patients with Grade IIIB open tibial fractures had
      definitive treatment of both the fracture and soft tissues performed within 72 h
      of injury. Free tissue transfer was used for cover in each case. There were no
      cases of deep infection. Flap survival was 100 per cent. The mean time to
      fracture healing was 10 months, and mean time to walking unaided was 12 months.
      The average length of stay in hospital was 82 days. The findings suggest that
      immediate radical debridement followed by adequate soft tissue cover is a safe
      and effective method for treating these severe injuries.

PMID- 9624334
TI  - Outcome in elderly injured patients: injury severity versus host factors.
AB  - To evaluate the differences between the outcome of elderly patients with severe
      injuries and that of their contemporaries with a less severe injury, we reviewed
      42 severely injured elderly patients and compared them with 76 patients with a
      femoral neck fracture. We analysed the influence of injury severity and host
      factors (age, sex and pre-injury medical status) on outcome. The in-hospital
      mortality rate was 31 per cent in the severely injured patients and 3 per cent in
      those with a femoral neck fracture. Home was the main discharge destination in
      the severely injured elderly (34 per cent) and a nursing home in patients with a
      femoral neck fracture (65 per cent). Functional outcome 1 year after injury was
      better in the severely injured elderly group. Long-term survival was mainly
      determined by host factors and not by injury severity. Physicians and policy
      makers should be careful in predicting the outcome of elderly injured patients
      merely on the basis of injury severity, because host factors are of greater
      importance.

PMID- 9624335
TI  - The shoelace technique for wound closure in open fractures: report of early
      experience.
AB  - A simple, reliable method of wound closure in open fractures is presented which
      has been used in this department. The necessity for split-skin grafting or flap
      cover, with the associated morbidity and cost implications, has been avoided by
      using this method. It has not been associated with any major complications in the
      patients studied, but it should be recognized that this method is not universally
      suitable in the treatment of all open injuries. We recommend this method as a
      simple way of achieving soft tissue cover in open injuries which are thoroughly
      debrided and cleaned, and in which there is no evidence of raised
      intracompartmental pressure.

PMID- 9624336
TI  - Percutaneous fluoroscopic screw fixation of acetabular fractures.
AB  - Over a 2-year period eight patients underwent percutaneous fluoroscopic fixation
      of their acetabular fractures. Average patient age was 43 and mean ISS was 27.
      Mean blood loss was less than 100 ml. There were five transverse fractures, one
      affecting both columns, one anterior column-posterior hemitransverse and one T
      type fracture. There were two ipsilateral femoral and two ipsilateral tibial
      fractures. Mean follow-up was 15 months. Three broad patient groups were
      identified. One patient died, one was lost to follow-up, four had full range of
      motion of the affected hip, one had good range with Brooker II heterotopic
      ossification and one was wheelchair-bound with Brooker IV heterotopic
      ossification. The technique, which requires only cannulated screws and
      fluoroscopy, is described.

PMID- 9624337
TI  - Modified medial displacement and valgus osteotomy for unstable intertrochanteric
      fractures.
AB  - We have described previously a modification of the medial displacement and valgus
      osteotomy of Dimon and Hughston to manage non-unions of intertrochanteric
      fractures. In this study, we have used the same modification to manage fresh,
      unstable intertrochanteric fractures. Eighty-seven patients underwent this
      procedure. Four died within 4 months. The remaining 83 patients were evaluated
      over a period ranging from 4 to 49 months. There was a low complication rate with
      this method. They included one perforation of the femoral head, one post
      operative infection that recurred as a deep infection, one partial superior
      migration of the implant, one varus fixation with noticeable shortening and two
      cases where the trochanteric wire had snapped. In the others, the hip movement,
      abductor function, functional recovery and rate of union (8-12 weeks) were good.
      The method permits early weight-bearing and avoids some of the problems seen with
      anatomical fixation of unstable fractures using the sliding screw plate. We feel
      that medial displacement and valgus osteotomy with an angled blade plate has a
      definite role in the treatment of unstable intertrochanteric fractures in some
      situations.

PMID- 9624339
TI  - Relative association of fever and injury with hypermetabolism in critically ill
      patients.
AB  - The purpose of this study was to determine the association of injury type
      (trauma, surgery, medical disease), systemic inflammatory response syndrome
      (SIRS) and fever with the degree of hypermetabolism in critically ill patients.
      Medical records of 204 critically ill, mechanically ventilated injured, surgical
      and medical patients were reviewed for indirect calorimetry and associated data.
      Analysis of variance and covariance was used to test the effects of injury, fever
      and SIRS on the degree of hypermetabolism. All injury types were found to be
      hypermetabolic. Analysis of variance of hypermetabolism with injury type and
      presence of fever as main effects revealed a significant increase in
      hypermetabolic response from fever, of similar magnitude across all injury types.
      Subjects with SIRS were significantly more hypermetabolic than subjects without
      SIRS. However, analysis of variance indicated no effect for SIRS but a
      significant effect for fever in increasing the hypermetabolic response. It is
      concluded that fever portends a magnification of the hypermetabolic response,
      being similar across injury types. SIRS does not identify hypermetabolic patients
      independent of fever. The host response to injury, not the injury itself,
      determines metabolic rate in critically ill patients. Neither SIRS nor injury
      type should be used to classify hypermetabolic states without stratifying for
      presence of fever.

PMID- 9624338
TI  - Predicting survival of victims of motor vehicle crashes in New York state.
AB  - This study assesses the relative ability of three different models to predict in
      hospital mortality for victims of motor vehicle crashes. The first two models,
      the trauma and injury severity score (TRISS) and a severity characterization of
      trauma (ASCOT), are models that have been used in many earlier studies and have
      been quoted extensively in the literature. The third model, which is developed in
      this study, uses essentially the same risk factors as the other two studies, but
      employs them in a different manner. In order to provide a fair comparison, new
      (logistic regression) model coefficients are fit to the first two models using
      the study data. The models are compared with respect to typical criteria for
      assessing the fit of logistic regression models as well as their ability to
      predict mortality for various subsets of seriously injured patients. The study
      concludes that the new model provides a substantially more accurate prediction of
      mortality, and that it may be wise for regions attempting to assess relative
      outcomes in their subregions to develop statistical models that are tailored to
      their own patients.

PMID- 9624341
TI  - The bony callus.
AB  - The bony callus was investigated by staining with the PAS and von Gieson
      techniques. The callus appeared to be composed of two adjoining but distinct
      types of bone. The birefringence observed in the periosteum and callus cartilage
      revealed different sized collagen fibres, each oriented perpendicularly to the
      long axis of the diaphysis.

PMID- 9624340
TI  - An evaluation of paramedic activities in prehospital trauma care.
AB  - The object of the study was to identify the effect paramedics have on prehospital
      trauma care and evaluate their influence on outcome compared to that of ambulance
      technicians. A prospective review of ambulance and hospital records was conducted
      over 2 years from 1 August 1993 to 31 July 1995. The setting for the study was
      the Royal Infirmary of Edinburgh and its primary response catchment area served
      by the South-East Region of the Scottish Ambulance Service central control room.
      The study involved 1090 patients brought to hospital by ambulance who met the
      entry criteria for the Scottish Trauma Audit Group study. The results show that
      paramedics spend significantly longer at scene than the ambulance technicians;
      however, there was no difference in total prehospital times between the groups.
      Paramedics direct a significantly higher proportion of patients to the
      resuscitation room and significantly more of these patients go to theatre,
      intensive care or the mortuary. There is no reduction in mortality or length of
      stay in intensive care in the paramedic group. The authors conclude that
      paramedics deliver an improved process of care but their activities do not
      significantly reduce mortality or length of stay in intensive care.

PMID- 9624342
TI  - Evaluation of a small trauma team for major resuscitation.
AB  - There has been a great improvement in the early management of trauma patients,
      encapsulated by ATLS. Initial in-hospital management of significant trauma is
      undertaken by a trauma team, the number and content of which varies. No study has
      demonstrated that large trauma teams per se improve patient survival, compared to
      smaller teams working in the same tertiary referral centre environment. This is a
      retrospective study of pedestrian road traffic accident patients, who were major
      resuscitation cases admitted over a 6-month period to this hospital, which is a
      Level I Trauma Centre. Most major trauma resuscitations are undertaken by a small
      trauma team, led by one doctor. The performance of the small trauma team was
      evaluated by applying TRISS methodology and comparing our patient group with MTOS
      (US). There were 77 patients. The majority (52 per cent) had polytrauma, 80 per
      cent required intubation, the median ISS was 27 and the median RTS was 5.03. Ten
      per cent required resuscitative procedures and 75 per cent required urgent
      surgery. Using TRISS methodology the Z statistic was +0.54 and the Unit's M
      statistic was 0.492. There were more unexpected survivors than deaths. Seventy
      one per cent were initially treated by one doctor. Only two patients had three or
      more doctors at the initial resuscitation. The use of small trauma teams within
      this Level I Trauma Centre does not appear to give results that are any worse
      than those of units that routinely use larger teams. This could be evaluated in
      other centres and may have implications for training, manpower and costing.

PMID- 9624344
TI  - Lateral closing wedge supracondylar osteotomy of humerus for post-traumatic
      cubitus varus in children.
AB  - Cubitus varus deformity following mal-union of a supracondylar fracture of the
      humerus in children causes no functional disability, but surgical correction is
      often requested to improve the appearance of the arm. Maintaining the correction
      after supracondylar osteotomy is a difficult aspect of the operative treatment
      and remains controversial. Nine children aged between 6 and 12 years (average 8
      years and 11 months) underwent lateral closing wedge supracondylar osteotomy of
      the humerus, for deformity ranging between 10 and 20 degrees (average 13
      degrees). The correction required ranged between 16 and 30 degrees (average 21
      degrees). The osteotomy was internally fixed with a two hole marrow plate. At
      follow-up, which ranged between 3 months and 6 years (average 34 months), six
      patients were graded as good, two as satisfactory and one as a poor result. One
      patient had transient radial nerve palsy which recovered completely in 2 months.
      The patient who was graded poor had undercorrection of the deformity at the
      original operation. There was no incidence of loss of correction due to implant
      failure. Complete section of the bone to allow medial displacement of the distal
      fragment is recommended, thereby avoiding lateral bony prominence at the elbow.

PMID- 9624343
TI  - Is it possible to predict limb viability in complex Gustilo IIIB and IIIC tibial
      fractures? A comparison of two predictive indices.
AB  - The patient with severe lower limb trauma presents a management dilemma; whether
      to amputate primarily or to attempt limb salvage. In recent years, many
      predictive indices have been published which purport to identify limbs which are
      non-viable. We retrospectively applied two recently described indices, the
      Mangled Extremity Severity Score (MESS) and the Limb Salvage Index (LSI), to 54
      limbs in 50 patients with either Gustilo IIIB or IIIC complex tibial fractures.
      There were 22 amputations (40.7 per cent) in the series. The mean MESS score in
      the limb salvage group was 3.8 (range 2-10), and the mean MESS score in the
      amputation group was 7.7 (range 4-13) (P < 0.0001). The mean LSI score in the
      limb salvage group was 3.6 (range 3-8), and the mean LSI score in the amputation
      group was 6.9 (P < 0.01). However, in the group with MESS scores > 7 (which
      recommends amputation), there were three limbs which were salvaged with
      acceptable functional outcome. Similarly, in those with LSI scores > 6 (which
      recommends amputation), there were seven limbs successfully salvaged. A MESS > 7
      offered a greater relative risk of amputation (9.2) than a LSI score > 6 (5.3).
      We found both indices of use in predicting limb salvage and functional outcome.
      However, neither is sufficiently accurate to be considered absolutely reliable in
      clinical practice.

PMID- 9624345
TI  - Surgical complications and implications of external fixation of pelvic fractures.
AB  - The application of a pelvic external fixator can be a vital stage in the
      management of patients with severe pelvic fractures, either as part of the
      resuscitation phase or as definitive treatment. This paper shows the complication
      rate of pelvic external fixation to be 47 per cent. This high rate increases the
      morbidity associated with the fracture, and may also interfere with the
      definitive management. The majority of complications were associated with pin
      placement and the pin-bone interface. An understanding of the principles of
      external fixation and knowledge of the correct methods of application should
      reduce this complication rate.

PMID- 9624346
TI  - Fracture incidence in England and Wales: a study based on the population of
      Cardiff.
AB  - Despite the importance of fractures as an economic and health problem, and
      consequent interest in osteoporosis, few workers have previously attempted to
      define the overall incidence of fracture. This population based study was based
      in the Accident and Emergency Department of Cardiff Royal Infirmary and
      identified all patients presenting with fractures of any type. Over a single year
      a total of 6467 fractures were identified among the 306,600 people who live in
      the city of Cardiff. This gives an overall fracture incidence of 21.1/1000/year,
      (23.5/1000/year in males and 18.8/1000/year in females); a result very similar to
      those from similar work in the USA, Australia and Norway. This result is over
      twice the previous estimate of fracture incidence in the UK; the figure of
      9/1000/year from the only equivalent study performed since the 1960s. In part,
      this discrepancy appears to reflect our more rigorous definition of the study
      population, and our improved ascertainment of minor fractures. We believe our
      result to offer the most accurate estimate of fracture incidence currently
      available for a UK population.

PMID- 9624347
TI  - Long-term results of pedicle stabilized thoracolumbar fractures in relation to
      the neurological deficit.
AB  - 88 patients with thoracolumbar fractures and short-segment (mono or two segment)
      pedicle instrumentation from the years 1985-92 had a follow-up examination after
      an average time of 5.6 years. The 56 men and 32 women had an average age of 32.6
      years at the time of injury, 24 patients primarily had a complete and 43 patients
      an incomplete paraplegia, 21 patients showed no neurological deficits. The
      operative decompression of the spinal cord and stabilization of the injured spine
      by short segment pedicle instrumentation led to a complete or partial remission
      of the neurological deficits in 93% of the patients with incomplete paraplegia.
      Operative stabilization allowed an early mobilization and rehabilitation of these
      patients. We found no tendency to an increased complication rate in patients with
      neurological deficits compared to patients without neurological deficits.
      Patients with initially incomplete paraplegia complained more often about pain
      than all the other patients. Despite intensive rehabilitation and retraining
      programs handicapped patients had obvious disadvantages regarding their further
      careers.

PMID- 9624348
TI  - Role of ultrasonography in blunt abdominal trauma.
AB  - Patients with blunt abdominal trauma (BAT) often have equivocal signs of intra
      abdominal injury. Diagnostic peritoneal lavage (DPL) has been the 'gold standard'
      for evaluating these patients, the use of ultrasound (US) being a recent
      phenomenon. Seventy-three patients with BAT and equivocal physical signs were
      subjected to both DPL and US for detection of intra-abdominal injury. Based on
      clinical status, DPL and US findings, the patients underwent laparotomy or non
      operative management. DPL was positive in 35 patients. There was one false
      positive and one false negative result (sensitivity 97.1%, specificity 97.4%,
      accuracy 97.3%). US was positive in 31 patients. There were 5 false positive and
      4 false negative results (sensitivity 86.7%, specificity 88.4%, accuracy 87.7%).
      Solid viscus injury was documented at laparotomy in 24 patients. DPL failed to
      detect one pancreatic injury, while US failed to detect 4 splenic and 2 liver
      injuries. US additionally detected a single case of haemopericardium. Although
      DPL outperformed US in this study, US can complement DPL in defining the organs
      injured and in follow up of patients undergoing non-operative management for BAT.

PMID- 9624349
TI  - Bilateral femoral neck stress fractures following steroid treatment.

PMID- 9624350
TI  - Lumbosacral nerve root avulsion.
AB  - Lumbosacral nerve root avulsion is a rare clinical entity. Since the first
      description in 1955, only 35 cases have been reported. It is often associated
      with pelvic fractures and may be missed in the initial clinical examination as
      these patients usually present with multiple injuries. We present three such
      cases with clinical and radiological findings. These patients were involved in
      road traffic accidents. Two had fractures of the sacroiliac joint with diastasis
      of the symphysis pubis (Tile type C 1.2) and one had fractures of the public rami
      (Tile type B 2.1). All three had various degrees of sensory and motor deficit of
      the lower limbs. Lumbar myelogram shows characteristic pseudomeningoceles in the
      affected lumboscral region. Magnetic resonance (MR) imaging provides an
      additional non-invasive modality to diagnose this condition.

PMID- 9624351
TI  - Traumatic aortic regurgitation.

PMID- 9624352
TI  - Bilateral traumatic chylothorax: a complication of a fracture of the thoracic
      spine.

PMID- 9624353
TI  - Non-union of a 'stable' AO type B ankle fracture.

PMID- 9624354
TI  - Abdominal and lower extremity crush syndrome.

PMID- 9624355
TI  - Kebab osteotomy of the tibia for a patient with osteopetrosis.

PMID- 9624356
TI  - Delayed infarction of the stomach following diaphragmatic injury.

PMID- 9624357
TI  - Removal of a broken intramedullary tibial nail using a hand reamer.

PMID- 9624358
TI  - Digital gangrene: an unusual late complication of non-union of a proximal humeral
      fracture.

PMID- 9624359
TI  - Asymptomatic persistent median artery in a trauma patient.

PMID- 9624360
TI  - Deep venous thrombosis in an injured child with an underlying thrombophilia--a
      case report.

PMID- 9624362
TI  - Isolated plantar dislocation of the middle cuneiform--a case report.

PMID- 9624361
TI  - Open reduction and internal fixation of an unusual multiple carpometacarpal
      dislocation using one plate: a case report.

PMID- 9624363
TI  - Intra-articular migration of a broken screw tip presenting as a locked knee.

PMID- 9624364
TI  - Dorsal dislocation of the distal interphalangeal joint with fracture of the volar
      base: an unusual type.

PMID- 9624365
TI  - Packing and temporary closure in a liver injury.
AB  - As a component of a staged laparotomy for trauma, perihepatic packing can be
      lifesaving in the patient with exsanguinating liver injury who, due to
      hypothermia and coagulopathy, is unable to tolerate a more extensive procedure.
      However, if intra-abdominal pressure increases, the manoeuvre has been reported
      to compromise cardiopulmonary stability. Patients who suffer the adverse
      consequences of intra-abdominal hypertension are commonly managed with a loose
      temporary closure, frequently using an artificial material to bridge the skin
      defect across the incision. A case is reported where these two seemingly
      contradictory options were combined to achieve a successful outcome.

PMID- 9624366
TI  - Minimizing the risk of guide-wire displacement during intramedullary reaming.

PMID- 9624367
TI  - A fail-safe method of inserting end caps into intramedullary nails.

PMID- 9624368
TI  - Compartment syndrome in victims of dog bites.

PMID- 9624369
TI  - Posterior fossa endoscopy.

PMID- 9624370
TI  - Basic techniques in molecular genetics.

PMID- 9624371
TI  - Benjamin Guy Babington and his mirror.
AB  - Despite good evidence to the contrary, the Spanish singing teacher Manuel Garcia
      is still credited by many to have been the discoverer of the mirror for
      inspecting the larynx. Although the adoption of this technique into clinical
      practice, and thus the beginning of laryngology as a specific discipline, is
      rightly credited to others Manuel Garcia achieved unwarranted fame ... if not
      fortune. Careful examination of the published literature has substantiated the
      claim that 26 years prior to the paper presented on Garcia's behalf to the Royal
      Society of London, Babington had described to the Hunterian Society a similar
      device which later evidence indicated had been used clinically on at least one
      laryngologist. This claim was also supported by no less than Morell Mackenzie in
      a published lecture in 1864, nine years after Garcia's lecture. Possible
      explanations for this aberration of justice are considered.

PMID- 9624372
TI  - Experimental studies on traumatic facial nerve injury.
AB  - PURPOSE: The purpose of this study was to investigate the outcome of different
      injuries to the facial nerve. MATERIALS AND METHODS: Six patterns of injuries
      (exposure, compression, crushing, stretching, division and post-division
      anastomosis) were produced in the buccal branches of the facial nerve in 60
      rabbits. Electroneuronography (ENoG) and histology at definite time were used to
      evaluate the results. RESULTS AND CONCLUSIONS: Exposure and compression injuries
      produced a neuropraxic injury and rapid recovery. Crushing and stretching
      injuries resulted in axonotmesis and whilst complete recovery can take place it
      may be very slow. Division and post-division anastomosis fall into neurotmesis
      injury and do not completely recover within six months; the former recovers
      slower and later than the latter.

PMID- 9624373
TI  - The effect of botulinum toxin type A injection for intrinsic rhinitis.
AB  - Botulinum toxin type A (BTA) is known to inhibit the release of acetylcholine
      from cholinergic nerve endings. Owing to the characteristics of BTA, we thought
      that it could be used for the treatment of intrinsic rhinitis acting as an
      anticholinergic drug. In a double-blind placebo-controlled study four units of
      BTA were injected into the middle turbinate (two units) and inferior turbinate
      (two units) in each nasal cavity. Rhinorrhoea, nasal obstruction, and sneezing
      were recorded in a symptom diary on the basis of a scale of 5 and the number of
      paper tissues used per day was also recorded for 24 weeks. Rhinorrhoea was
      significantly diminished in severity (24.1-41.5 per cent reduction) and paper
      tissue use (54.3 per cent reduction) in the BTA group compared with the placebo
      group. This effect could be maintained for four weeks. Sneezing and nasal
      stuffiness were not affected by BTA. These results suggest that BTA can be used
      to treat rhinorrhoea in intrinsic rhinitis patients, however, the effective
      period is short.

PMID- 9624374
TI  - Second primary cancer of the larynx in patients with lung cancer.
AB  - Synchronous or metachronous second primary malignancies of the lung are sometimes
      encountered in patients with laryngeal cancer while the occurrence of a laryngeal
      second primary following cancer of the lung is rare. A two-armed study was
      conducted. A prospective arm in which the larynges of 56 terminal lung cancer
      patients were examined, and a retrospective arm incorporating both a chart study
      of 126 terminal head and neck cancer patients (HNCP) and a computerized search of
      all hospital records of patients with laryngeal and lung cancers. No laryngeal
      malignancy was found in the lung cancer patients' group and no antedating
      pulmonary malignancy was recorded in the terminal HNCP. The computerized search
      of 1778 lung cancer patients and 213 laryngeal cancer patients also failed to
      demonstrate cases where the former preceded the latter. In conclusion. No second
      primary of the larynx was found in lung cancer patients. These results compare
      with reports of large databases where cancer of the larynx was found in a
      negligible percentage of lung cancer survivors and theories explaining this are
      discussed.

PMID- 9624375
TI  - Assessment of distress associated with tinnitus.
AB  - This paper focuses upon the quality of the Dutch translation of the STSS
      (Subjective Tinnitus Severity Scale), a scale which assesses the severity of
      tinnitus and the related distress. Research has been done on the psychometric
      qualities of this scale, its relationship with loudness-matching procedures and
      several psychological variables. Data presented on 104 tinnitus patients
      demonstrated the reliability of the STSS with a coefficient alpha of 0.71. Factor
      analysis revealed four factors: emotional distress, intrusiveness, annoyance and
      cognitive distress. With regard to the validity, significant correlations of a
      moderate degree were found with several unitary subjective scales measuring the
      same construct (rs = 0.50, p < 0.001 and rs = 0.43, p < 0.01). Correlational
      research demonstrated that the STSS is independent of the loudness of tinnitus as
      measured by matching procedures (rs = 0.00). In contrast, significant
      correlations of a moderate magnitude were found with anxiety (rs = 0.33, p <
      0.001) and depression (rs = 0.31, and rs = 0.35, p < 0.001).

PMID- 9624376
TI  - Antibiotic choice in acute and complicated sinusitis.
AB  - The microbiology of 87 patients admitted to hospital, over a five-year period,
      with acute sinusitis was retrospectively analysed. Sixty-three patients had one
      or more of an orbital, intracranial, soft tissue or bony complication. Eighty
      four patients had maxillary sinus washouts, while 48 required a surgical
      procedure to their sinuses, and 33, drainage of an empyema. Streptococcus milleri
      and Haemophilus influenzae were the commonest organisms isolated from sinus
      aspirates (44 per cent), with a noticeable absence of Streptococcus pneumoniae
      (10 per cent). Organisms cultured from intracranial, soft tissue or orbitral
      empyemas were predominantly Streptococcus milleri (50 per cent) and
      Staphylococcus aureus (25 per cent) with an absence of Haemophilus influenzae
      (four per cent) and Streptococcus pneumoniae (four per cent). Ampicillin is an
      appropriate first line antimicrobial agent in patients with acute complicated
      sinusitis with the addition of cloxacillin in cases with an empyema.
      Chloramphenicol or ceftriaxone is used in cases with an intracranial
      complication.

PMID- 9624377
TI  - Submandibular gland excision: a five-year review.
AB  - Excision of the submandibular gland is a surgical procedure often undertaken. The
      procedure is the treatment of choice for patients with neoplasm of the
      submandibular gland and those with non-neoplastic submandibular disorders which
      are not controlled with conservative medical measures. Extirpation of the
      submandibular gland may also be undertaken for diagnostic purposes. This
      retrospective study of 93 consecutive patients who underwent excision of the
      submandibular gland in the Department of Otolaryngology, Singapore General
      Hospital over a five-year period was undertaken to study the indications of
      surgery, the pathology of the excised submandibular gland and the demographic
      profile of patients. Fifty-six (60.2 per cent) patients underwent submandibular
      gland excision for non-neoplastic salivary gland disease while 37 (39.8 per cent)
      had neoplastic submandibular gland disorders. The commonest pathology encountered
      was sialadenitis/sialolithiasis (53.76 per cent) followed by pleomorphic adenoma
      (33.33 per cent). Fine needle aspiration cytology (FNAC) was a valuable pre
      operative investigation with a sensitivity and specificity of 94.7 per cent and
      100 per cent respectively for neoplastic disease. The morbidity rate for this
      surgery was 4.3 per cent.

PMID- 9624378
TI  - Malignant otitis externa with optic neuritis.
AB  - Malignant otitis externa is a serious condition that presents difficulties in
      treatment, and also in monitoring its progress. A case of malignant otitis
      externa with optic neuritis is presented that remained refractory to standard
      treatment but was cured by adjuvant hyperbaric oxygen therapy. This is the only
      reported case that has survived this disease with optic neuritis. The usefulness
      of imaging techniques in this condition is discussed, as well as the ESR, in
      evaluating the effectiveness of treatment.

PMID- 9624379
TI  - Chondroma of the external auditory canal.
AB  - Chondroma, a benign tumour which is common at many sites in the body, has not
      been reported in the English literature in the bony external auditory canal. The
      first such case at this anatomical site is described and the pathogenesis is
      considered.

PMID- 9624380
TI  - Kaposi's sarcoma masquerading as pyogenic granuloma of the nasal mucosa.
AB  - Kaposi's sarcoma (KS) is a neoplastic vascular disorder characterized by multiple
      reddish blue nodules which, according to the original description (Kaposi, 1872),
      usually present on the skin of the upper and lower extremities. It is not until
      the disease progresses that nodules appear on the skin of the head and neck, on
      mucosal membranes and as visceral lesions. However, with the large increase in
      the incidence of this tumour associated with the acquired immune deficiency
      syndrome (AIDS) epidemic, there have been increasing numbers of cases of Kaposi's
      sarcoma presenting primarily on the skin or mucosa of the head and neck. The most
      common sites reported are within the oral cavity, particularly on the palate.
      Other mucosal sites are rare. We present an unusual case where the primary
      manifestation of the Kaposi's sarcoma was in the nasal mucosa and stress the
      importance of this diagnosis not being overlooked.

PMID- 9624381
TI  - Ethmoid metastasis of endometrial carcinoma causing mucocoele of maxillary
      antrum.
AB  - We report a case of an antral mucocoele secondary to the obstruction of its
      ostium by metastatic endometrial carcinoma. This is the first report of such a
      cause for a mucocoele, and for a metastasis from such a tumour in the head and
      neck.

PMID- 9624382
TI  - Solitary fibrous tumour of the larynx: report of a case.
AB  - Solitary fibrous tumour is a particular kind of mesenchymal tumour, classically
      arising in the pleura. We report the first case arising in the larynx, associated
      with a metastasizing adenocarcinoma. The diagnosis is mainly histopathological,
      especially when strong immunoreactivity for the CD34 antibody is present.

PMID- 9624383
TI  - Angiomyoma of the retropharyngeal space.
AB  - We encountered a 59-year-old man with angiomyoma of the retropharyngeal space. He
      had been referred to our hospital because of a six-month history of a sensation
      of a narrowed pharynx. A smooth-surfaced tumour arising from the posterior wall
      in the hypopharynx was observed by indirect laryngoscopy. Radiographical imaging
      revealed a solitary tumour with homogenous contents in the retropharyngeal space.
      The tumour was successfully removed via a lateral pharyngotomy approach under
      general anaesthesia. Histopathologically, the tumour was composed of numerous
      veins with thick muscular walls. To the best of our knowledge, this is the first
      report of an angiomyoma arising in the retropharyngeal space.

PMID- 9624384
TI  - Soft tissue chondroma of the parapharyngeal space: a case report.
AB  - Benign chondroma affecting the soft tissues is uncommon. This tumour is
      particularly rare in the neck. We present the first case of soft tissue chondroma
      arising in the parapharyngeal space of a 20-year-old man with a two-year history
      of a gradual sensation of a swelling in the pharynx with increasing snoring. The
      CT and pathological features of this lesion will be discussed. We suggest that a
      peroral approach should be considered for benign parapharyngeal tumour which has
      been demonstrated on imaging to be in the anterior parapharyngeal space,
      especially for tumours that are medial to the pterygoid muscles even though the
      tumour is a large one.

PMID- 9624385
TI  - An unusual complication of chemotherapy: an abscess in the pterygopalatine fossa.
AB  - Abscesses of the pterygopalatine fossa are extremely rare. The cases reported in
      the literature are all secondary to dental or periodontal disease. We present a
      case of an abscess in this site which was a complication of chemotherapy and was
      the result of haematogenous spread.

PMID- 9624386
TI  - Cervical necrotizing fasciitis and radiotherapy: a report of two cases.
AB  - Two cases of cervical necrotizing fasciitis are presented. Both are unusual in
      that they had had radiotherapy for head and neck malignancy six and 14 years
      previously with no evidence of tumour recurrence. One case of necrotizing
      fasciitis has previously been cited in the literature associated with
      radiotherapy (Krespi et al., 1981). The two cases are discussed along with a
      review of the literature.

PMID- 9624387
TI  - Parapharyngeal emphysema--an unusual complication of temporal bone trauma.
AB  - We report a case of a 36-year-old woman who suffered a temporal bone trauma due
      to a bicycle crash. Computed tomography revealed parapharyngeal emphysema despite
      only minor temporal bone changes.

PMID- 9624388
TI  - The use of positron emission tomography and computed tomography in the assessment
      of trismus associated with head and neck malignancy.
AB  - The assessment of head and neck cancer has traditionally involved clinical
      examination and anatomical imaging by computed tomography (CT) or magnetic
      resonance imaging (MRI). We present a case where a problem of clinical confusion
      and inconclusive radiology was resolved by the use of positron emission
      tomography (PET) coregistered with CT.

PMID- 9624389
TI  - Idiopathic midline destructive disease--does it exist?
AB  - There is controversy whether idiopathic mid-line destructive disease remains a
      valid entity, some authors considering that such cases are unrecognized malignant
      lymphoma or Wegener's disease. A case is presented in which numerous nasal
      biopsies over several years failed to show evidence of either lymphoma or
      Wegener's disease. Molecular genetic analysis of archival tissue did not
      demonstrate a monoclonal lymphoid population. It is proposed that idiopathic mid
      line destructive disease remains a valid description in a small number of cases.

PMID- 9624390
TI  - Proliferating cell nuclear antigen in laryngeal cancer.
AB  - The expression of proliferating cell nuclear antigen in paraffin sections from
      154 cases of laryngeal squamous cell carcinoma were examined. There was
      significant difference in PCNA expression between the control group and cancer
      patients (p < 0.001). The mean score of PCNA was higher in patients with poor
      prognosis than in patients with satisfactory outcome after treatment (p < 0.05).
      There was no significant correlation between the PCNA count and the patient's age
      and sex, T and N stage and site of the tumour. Univariate analysis revealed that
      the PCNA score correlated with the patients' survival rates. In multivariate
      analysis the prognostic value of PCNA was on the statistical borderline (p =
      0.049). In our study clinical features like N and T status had a more important
      influence on survival rate. Nevertheless it appears that the immunohistological
      examination of PCNA in paraffin section could be a complementary prognostic tool
      for laryngeal carcinoma. PCNA expression may also be a valuable tool for
      differentiating malignant from benign laryngeal epithelium.

PMID- 9624391
TI  - Partial truths--research papers in medical education.

PMID- 9624392
TI  - Barriers to acceptance of medical error: the case for a teaching program (695).
AB  - There is need for a teaching programme aiming to impart a tolerance of error to
      undergraduate medical students. The implementation of such a programme may have
      to challenge the institutional norms that encourage authoritarianism, intolerance
      of uncertainty and denial of error. Acceptance of error is a prerequisite for its
      candid reporting, and reporting of errors is a prerequisite for their analysis
      with a view to their prevention. A curriculum on medical error may, therefore,
      not only help medical students cope with their future mistakes, but also reduce
      their frequency. Teaching intervention aiming to promote an acceptance of medical
      error as both inevitable and reducible may also encourage students'
      epistemological development by making them realize that their doubts and
      uncertainties are shared by their peers and instructors.

PMID- 9624393
TI  - Standardized patients in the assessment of general practice consulting skills
      (694).
AB  - This paper describes the use of standardized patient interviews as a means of
      assessing the consulting skills of fifth year medical students studying general
      practice. Interviews are restricted to a duration of 9 minutes and focus on
      either diagnostic or management tasks. Volunteers are trained to play
      standardized roles depicting common general practice presentations. A detailed
      marksheet has been developed to increase inter-examiner reliability, discourage
      global marking and incorporate a patient assessment of the student. Issues of
      reliability, validity and security in this form of assessment are discussed.

PMID- 9624394
TI  - Critical thinking: change during medical school and relationship to performance
      in clinical clerkships.
AB  - The development of critical thinking, the ability to solve problems by assessing
      evidence using valid inferences, abstractions, and generalizations, is one of the
      global goals advocated by most medical schools. This study determined changes in
      critical thinking skills between entry and near the end of the third year of
      medical school, assessed the predictive ability of a test of critical thinking
      skills, and assessed the concurrent validity of clerkship components and final
      grade. The Watson-Glaser Critical Thinking Assessment (WGCTA) was administered to
      one class of students at entry to medical school and near the end of year 3.
      Performance data for those students who completed their clinical clerkships on
      schedule were also recorded. Critical thinking improved modestly but
      significantly from entry to medical school to near the end of year 3. The ability
      of a critical thinking test to predict clerkship performance was limited; the
      correlation between WGCTA total score at entry and the components and final grade
      of five major clerkships ranged from near 0 to 0.34. The concurrent validity of
      clerkship components and final grade was also limited; correlations with WGCTA
      total score near the end of year 3 ranged between 0.08 and 0.49. The correlation
      between WGCTA total score and United States Medical Licensing Examination Step 2
      was higher at year 3 than at medical school entry. Critical thinking skills
      improve moderately during medical school. Used alone, tests of critical thinking
      may be of limited value in predicting which students will be successful in
      clinical clerkships. Clerkship evaluation components and final grade have limited
      concurrent validity when a test of critical thinking is the criterion.

PMID- 9624395
TI  - Do junior doctors feel they are prepared for hospital practice? A study of
      graduates from traditional and non-traditional medical schools.
AB  - A valid and reliable questionnaire was developed which assesses eight subscales
      relating to key areas of medical hospital-based work. This was used to evaluate
      junior doctors' perceptions of the adequacy of their undergraduate medical
      training to prepare them for hospital practice. Data from 139 (60%) first-year
      doctors (interns) showed that graduates from the problem-based medical school
      rated their undergraduate preparation more highly than traditional medical school
      graduates in preparing them for practice in the areas of interpersonal skills,
      confidence, collaboration with other health care workers, preventive care,
      holistic care and self-directed learning. These findings persisted when ratings
      were adjusted for the effects of age and gender. There were no differences
      between the intern groups for patient management and understanding science. This
      research suggests that educational experiences in different undergraduate medical
      courses are important in preparing doctors for their early working life.

PMID- 9624396
TI  - A survey of communication skills training in UK schools of medicine: present
      practices and prospective proposals.
AB  - It is now widely accepted that effective interpersonal communication is at the
      heart of quality health care delivery but that current standards in medicine must
      be improved (Numann 1988; Cowan et al. 1992). One approach acknowledged by the
      General Medical Council (1991) devotes more attention during training to the
      theme of communication, and quite significant modifications of the undergraduate
      medical curriculum are presently taking place. This article documents the results
      of a postal survey of the 26 UK Schools of Medicine, designed to illuminate
      current practices and future plans in respect of communication skills training
      (CST). As such, it takes advantage of the present period of ongoing curricular
      innovation and change to extend and update earlier reviews (Whitehouse 1991;
      Frederikson & Bull 1992). A total of 19 responses was received. Following
      preliminary analysis, the four schools who had already implemented their new
      curriculum were selected for further in-depth investigation by means of telephone
      interviews. In addition to reporting frequencies and percentages for responses to
      questions, cross-tabulations were carried out to explore relationships between
      certain of the findings. Apart from some consistency in CST teaching methods
      adopted, the overall picture to emerge is one of considerable variability in such
      areas as course content, timing, duration and assessment. Foremost among the
      difficulties encountered in implementing CST appeared to be lack of adequate
      physical resources and suitably trained staff. Future plans were often sketchy
      and inchoate. Results are discussed and tentative recommendations for the further
      development of CST in the medical curriculum proffered.

PMID- 9624397
TI  - An innovative problem-solving assessment for groups of first-year medical
      undergraduates--Think Tanks.
AB  - A problem-solving assessment has been devised and used for groups of first-year
      medical students at Southampton University. Five cohorts of approximately 160
      students have taken the assessment since 1990. The assessment was part of a
      Locomotor system course that integrated biological and behavioural sciences and
      clinical specialties. The course also included lectures, practicals and tutorials
      and occupied the first 7 weeks of the last (10-week) term. Other assessments of
      the course involved essay writing and a spotter-type practical. For the problem
      solving assessment, groups of about six students ('Think Tanks') received a
      problem which they had to investigate during the course. The students had some
      choice in the problem they were to study. The problems were designed, by staff,
      to cover aspects of movement in the context of health and disease. A staff
      advisor was assigned to each Think Tank group to provide general support. The
      results of the investigations of each Think Tank were displayed at the end of the
      course in the form of a poster aimed at informing their peers. Three members of
      staff gave each Think Tank group a communal oral examination and the performance
      of the group was given a grade. Each member of the group, normally, was allowed
      to add this grade to their marks for the whole year.

PMID- 9624398
TI  - The relationship between assessment measures at Newcastle Medical School
      (Australia) and performance ratings during internship.
AB  - This study examined the utility of the domain assessment measures used in the
      final 2 years at Newcastle medical school in predicting performance ratings in
      the first year of postgraduate training (internship). Performance ratings were
      obtained from the clinical supervisors of two graduating classes of the
      University of Newcastle medical students during their five terms of internship.
      Three or more ratings were obtained from 57% of interns. Univariate analysis
      indicated that scores for three of the five domains (professional skills;
      identification, prevention and management of illness; self-directed learning)
      were significantly positively correlated with intern performance ratings.
      Multivariate analysis indicated that only the domain assessing identification,
      prevention and management of illness was predictive of higher intern performance
      ratings. The results support the notion that there is some value in the domain
      assessment model used at Newcastle in predicting the performance of junior
      doctors.

PMID- 9624399
TI  - Change in student attitudes to medical school after the introduction of problem
      based learning in spite of low ratings.
AB  - Students' attitudes to, and opinions of, their studies at medical school were
      investigated with the help of a questionnaire. They were asked to what extent the
      medical school encouraged independent, critical thinking, problem-solving skills,
      decision-making, studying outside the textbook and other behaviours and skills
      that teachers in higher education usually put forward as important. It was found
      that students generally had a low opinion of the extent to which their education
      encouraged such virtues, mean figures ranging between 3.5 and 4.6 on a 10-grade
      scale. The students felt that their studies to a large extent encouraged focus on
      details and preparation for examinations. The questionnaire was given to the
      students after 2 1/2 years of traditional preclinical studies and at the end of
      the first clinical year. There were significant but numerically small differences
      for some of the items at the end of the year. However, when problem-based
      learning (PBL) was introduced during the first clinical year, there was a
      substantial change: there were now significant and numerically larger differences
      for seven of the nine items, even though the students were asked to give their
      opinion of the whole of their time at medical school on both occasions, not only
      of the last year. There were no other changes in the curriculum or the teaching
      methods other than the introduction of PBL. The change in attitudes did not
      depend on the student's appreciation of PBL; students' opinion of PBL was low,
      indicating that most of them disliked it.

PMID- 9624400
TI  - Student assessment in community settings: a comprehensive approach.
AB  - Student assessment in community settings presents problems for medical teachers,
      e.g., difficulties in assessing the contribution of individual members to group
      work, and lack of test standardization due to varying field conditions. The
      Faculty of Medicine, University of Gezira, Sudan is a community-oriented,
      community-based medical school which has adopted a comprehensive approach to
      student assessment in community settings using various methods, including peer
      assessment, a supervisory checklist, community feedback, reports from students,
      short essay questions (SEQs) and multiple choice questions (MCQs). Each method
      focuses on a specific aspect of the objectives of the community-based programme
      and is weighted in the final grade according to the extent to which objectives
      were covered. This assessment programme contrasts with the conventional teacher
      centred approach, and is continuously monitored and improved using a variety of
      sources of information. A total of 105 students participated in a study designed
      to measure the reliability and validity of this approach. The reliability of the
      methods was tested by computing the alpha coefficient and was found to range
      between 0.77 and 0.92. This was considered acceptable. The validity of the
      instruments was examined using confirmatory factor analysis, and their content
      validity was reviewed. The results show that the comprehensive approach used is
      fairly valid. It is suggested that the University's approach is successful in
      solving some of the problems of student assessment in community settings.

PMID- 9624401
TI  - Collaboration between specialties: a US and European experience.
AB  - Inter-departmental experiences in endocrinology at the Pennsylvania State
      University College of Medicine, Hershey, Pennsylvania, and the National
      University Hospital, Copenhagen, Denmark are described. These co-operative units
      maximize specialty resources for patient care, teaching and research, and
      constitute an organizational format now appearing in inter-disciplinary centres
      of excellence. Many perceived threats to academic-based endeavours may be aided
      by greater collaboration between traditional specialty groupings, particularly
      the primary care oriented departments of medicine and paediatrics.

PMID- 9624402
TI  - Comparison of the opinion of students and teachers concerning medical education
      programmes in Switzerland.
AB  - Three medical schools in Switzerland (Geneva, Lausanne and Bern) have recently
      started to implement a problem-based learning community-oriented reform. It
      seemed worthwhile to attempt to identify the opinion of those who would be
      concerned (teachers and students) before any changes were made. Data were
      collected through interviews and questionnaires on the seven following themes:
      (i) community-oriented education; (ii) professional profile; (iii) learner
      centred education; (iv) teachers' educational competence; (v) coveritis; (vi)
      problem-based learning; and (vii) programme evaluation. The opinions of teachers
      and students were also compared with the position taken by specialists in medical
      education. The aim of this article was to present the key finding of this complex
      research. Interested readers are invited to refer to the full report.

PMID- 9624403
TI  - Evaluation of a national and international distance education program in clinical
      epidemiology (691).
AB  - Distance education (DE) has been used as a teaching mode for over 100 years for a
      variety of academic, vocational and recreational courses. This paper describes a
      postgraduate clinical epidemiology course conducted by DE for Australian and
      international health professionals, and compares the educational experiences of
      three groups of students (on-campus part-time, Australian DE and international
      DE). The groups were not expected to differ in academic achievement (marks) in
      eight subjects or in degree completion rates. The marks in each subject were not
      significantly different and typically were within five marks across all student
      groups. Approximately 40-50% of Australian DE students complete the graduate
      diploma coursework requirements in the minimum 2 years study. The completion rate
      increases to 70-80% as the period of candidature increase. The completion rates
      of Australian DE students were not significantly different from those of on
      campus part-time students. Evaluation of the course by degree completion rates,
      comparison of academic achievement between off-campus and on-campus students, and
      qualitative feedback from students demonstrates that DE is as successful as on
      campus teaching in providing training in clinical epidemiology at the
      postgraduate level. The flexibility of this mode of training as a means of
      providing public health training is discussed.

PMID- 9624404
TI  - Gynaecological examination: a teaching package integrating assessment with
      learning (693).
AB  - A self-directed learning package which includes assessment was developed to allow
      students to acquire the psychosocial and motor skills needed to conduct a
      gynaecological examination with sensitivity. The package integrates assessment
      with learning and uses the Assessment Form as an educational instrument. The
      introduction, including a video of a vaginal examination and pap smear, is
      followed by five learning stations for groups of 3 or 4 students to visit. At
      each station a series of tasks are given which enable the objectives of the
      station to be fulfilled. The materials necessary to complete the tasks are
      provided. Gynaecological assistants, themselves trained by participation in the
      learning sessions, guide the students throughout the session and act as adviser
      'patients' to help students acquire the necessary motor skills. In the
      assessment, students are required to integrate what they have learnt in the
      learning stations. The students assess themselves and the 'patient' and an
      observer assesses the student using the same Assessment Form. The form assesses
      and gives examples of the psychosocial, including legal and motor skills
      required. The assistants-observers give feedback to the students about their
      performance and make suggestions for future improvement. Of the 232 medical
      students completing their clinical terms in Obstetrics and Gynaecology in 1995,
      those students receiving the learning package rated their practical experience as
      significantly better. They rate the learning method, content, enjoyment and
      package overall very highly (median 4, 5 point scale 1-5). Open-ended comments by
      students confirmed these findings.

PMID- 9624405
TI  - International collaboration in the development of postgraduate research training
      (692).
AB  - Research training leading to a higher degree can be difficult for those who live
      in countries where advanced educational facilities are not yet available, since
      it may involve translation of a whole family to a foreign country with resultant
      language, financial and cultural problems. There are special difficulties for
      females and those of the Moslem faith, who may have been married early and
      already have a family by the time of initial graduation. There may also be
      cultural difficulties preventing overseas study for the unmarried female. This
      paper describes a flexible approach developed by the University of Aberdeen in
      association with the Ministry of Health in Kuwait. This was an MSc course on the
      process of continuous quality assurance in medical practice which was based on
      the concept that research training was the best means of evaluating and measuring
      quality. The students were finally assessed on the quality of their research
      dissertation. The course, which was part-time, and thus lasted for 2 years,
      required them to spend 12 weeks in each of two successive summers in Aberdeen.
      The subject chosen for each dissertation was related to the work area of the
      candidate and was studied in the country of origin with the help of periodic
      visits by the supervisors. The results were surprisingly successful since the
      students became highly motivated by the problems of their own country and were
      encouraged by their colleagues at home. The process could have been even more
      successful if videoconferencing facilities had been available at both the
      Aberdeen and Kuwait centres. It is concluded that a more flexible approach by
      western universities would result in an increase in both the quantity and the
      quality of postgraduate study.

PMID- 9624406
TI  - General practice in the curriculum in Slovenia.
AB  - Specific education in primary care in Slovenia developed in 1966, when vocational
      training for general practitioners was introduced. However, general practice
      never gained academic acceptance and was not introduced as a separate subject at
      undergraduate level. With the reform of medical education in Slovenia starting in
      1987, family medicine was finally introduced as a specific subject in the final
      year. The new curriculum introduced a strong emphasis on practice-based teaching
      and in 1995 the first university department of family medicine was formally
      established. This article reports the first evaluation of the programme, based on
      qualitative and quantitative analysis of questionnaires, from students and the
      general practitioners who were their tutors. The programme was very well accepted
      by the students, who enjoyed working independently in a friendly environment
      where their tutors were more facilitators than teachers. The main problem is
      recognition of tutors by the medical and educational establishment, which will
      motivate tutors to perform additional educational tasks in the future.

PMID- 9624407
TI  - Development and evaluation of a computer-aided learning package for minor oral
      surgery teaching.
AB  - 'Aspects of Minor Oral Surgery' is a highly interactive software program that was
      commissioned by the Department of Health, England, as part of the continuing
      education opportunities of general dental practitioners. The content of the
      program is also suited to the education of senior clinical dental students. The
      beta (pre-release) version was evaluated by 67 general dental practitioners, who
      completed a questionnaire on aspects of the program's functionality. Responses on
      its usefulness as an educational tool were 78% positive and 4% negative. In
      comparing the program to other educational media on the same subject, 77% felt it
      was better than video, 69% said it was better than textbooks, and 80% preferred
      it to journals. Its main strengths were judged to be the high level of
      interactivity, the ease of navigation and use, and the quiz section. The quality
      of the images of surgical procedures displayed in the slide shows was judged to
      be a weakness, and this problem was addressed in preparing the final version. Ten
      UK academic and four health service senior oral surgeons were also asked to give
      feedback on the program's content, and these points were also incorporated in the
      final text. More than 1,600 copies of the program have been taken up by general
      dental practitioners so far. The program may be downloaded for evaluation via the
      internet.

PMID- 9624408
TI  - Neurobehaviour rounds and interdisciplinary education in neurology and psychiatry
      (698).
AB  - Increasing emphasis on interdisciplinary medical treatment and education suggests
      that something valuable has arisen from medical specialization beyond the further
      development of specialty knowledge: an integration of specialty knowledge that
      compliments and extends the integrating aspects of the primary care approach to
      medicine. Several educational models have been described which serve this
      function. In this paper the authors describe interdisciplinary clinical teaching,
      and research team linking neurology, neuroradiology, psychiatry and
      neuropsychology. The team provides neurobehavioural evaluations and sponsors
      monthly Neurobehaviour Rounds, an interdisciplinary patient conference that is
      the main formal teaching vehicle for the programme. After the model had been in
      place for 1 year, eight of nine neurology residents had Residency In-Service
      Training Examination scores in behavioural neurology that exceeded their overall
      average scores. This suggests that encouraging neurology residents to see
      patients through the eyes of different specialists may have contributed to
      improvement in their performance on a test of interdisciplinary knowledge. A
      neurobehavioural programme anchored to a formal neurobehaviour conference may
      encourage interdisciplinary learning within the related disciplines of neurology,
      neuropsychology and psychiatry.

PMID- 9624409
TI  - Postgraduate education in medical ethics in Japan.
AB  - The objective of this paper was to investigate what kind of postgraduate
      education in medical ethics medical residents in Japan receive and what they want
      for ethical education and guidelines. Sixteen teaching hospitals that provide a
      general internal medicine residency programme in Japan were used (145 medical
      residents working at the departments of general internal medicine). A total of
      114 residents participated in our survey, yielding a response rate of 79%. Of
      these, 28% received education in medical ethics more than once a month; 24% were
      offered it only when ethical problems were involved in actual patient care; and
      18% answered that opportunities were very rare and sporadic. A full 30% had
      received no education in medical ethics at all. Many residents (71%) learned
      medical ethics from individual supervising doctors. A majority of the residents
      had been taught about informed consent (79%) and doctor-patient relationships
      (54%); 46% had learned about the appropriateness of truth telling and of ethical
      decisions regarding withholding and withdrawing a life-sustaining treatment,
      respectively. A total of 85 residents (75%) wanted to have more comprehensive
      education in medical ethics, 13% could not decide, and 12% did not want it. Many
      (66%) thought that both doctors and ethical philosophers should jointly teach
      medical ethics in postgraduate residency programmes. The results suggest that
      many residents desire more comprehensive and interdisciplinary education in
      medical ethics and educators in Japan should aim to develop education programmes
      to meet these desires.

PMID- 9624410
TI  - Reducing variability in treatment decision-making: effectiveness of educating
      clinicians about uncertainty.
AB  - The objective of this study was to investigate whether or not education about the
      concept of uncertainty reduced variability in treatment decision-making. Three
      small groups of dentists in North York, Canada were asked to make restorative
      treatment decisions about simulated bitewing radiographs. They subsequently took
      part in a seminar about variations in perception and judgement and were given
      explanations of sensitivity, specificity and receiver operating characteristic
      (ROC) curve analysis. A repeat reading of the radiographs was then performed by
      both test and control groups. Results indicated that the intervention increased
      the accuracy, and decreased the variability of dentists' restorative treatment
      decisions. Kappa statistics were 0.33, 0.34 and 0.31 before the seminar, and
      0.40, 0.43 and 0.41 after the seminar. Standard errors for kappas were 0.06, 0.05
      and 0.05 before the seminar, and 0.02, 0.02 and 0.05 after the seminar. The area
      under the ROC curve was 0.7136 before the seminar and 0.7835 after the seminar.
      The data demonstrate that the dentists' decisions were less variable and more
      accurate following the educative intervention. This study suggests that there is
      potential for improving consistency and accuracy in clinical decision-making
      through education in probabilistic reasoning.

PMID- 9624411
TI  - Re: What can universities do to reverse the decline in the numbers of doctors
      entering general practice? (Sullivan & Morrison 1997)

PMID- 9624413
TI  - Demystified ... in situ hybridisation.

PMID- 9624414
TI  - Identification of HHV8 in early Kaposi's sarcoma: implications for Kaposi's
      sarcoma pathogenesis.
AB  - AIMS: Kaposi's sarcoma is a vascular tumour of uncertain pathogenesis possibly
      caused by an infectious agent, identified in high risk groups. Accumulating
      solution phase polymerase chain reaction (PCR) and seroepidemiological data
      suggest that a previously undescribed herpes DNA virus (human herpesvirus 8
      (HHV8)) is the causative agent. Using a unique cohort of early Kaposi's sarcoma,
      the precise cell type infected with HHV8 in such lesions was identified to
      elucidate further the role of HHV8 in the pathobiology of Kaposi's sarcoma.
      METHODS: Sixteen cases of early Kaposi's sarcoma (derived from skin and lymph
      node) were assessed for the presence of HHV8 using both standard solution phase
      PCR and TaqMan PCR to the KS330 Bam region of HHV8. In situ amplification was
      also performed on a selected group in an attempt to identify the candidate
      infected cells. RESULTS: Using both conventional solution phase and TaqMan PCR,
      87% of cases were positive. In addition, HHV8 amplicons were localised in situ to
      endothelial and spindle cell proliferations in early Kaposi's sarcoma. The HHV8
      viral load varied from lesion to lesion. CONCLUSIONS: The presence of HHV8 in
      early lesions supports a role for HHV8 in the pathogenesis of Kaposi's sarcoma.
      Coupled with recent seroepidemiological studies, these results suggest that HHV8
      is the aetiological agent of Kaposi's sarcoma. Its precise interaction with other
      factors known to be involved in the development of Kaposi's sarcoma, including
      cytokines and anti-apoptosis genes, requires elucidation.

PMID- 9624412
TI  - Cyclin D1 and human neoplasia.
AB  - Neoplasia is characterised by abnormal regulation of the cell cycle. Cyclin D1 is
      a protein derived from the PRAD1, CCND1 or bcl-1 gene on chromosome 11q13, which
      is involved in both normal regulation of the cell cycle and neoplasia. In the G1
      (resting) phase of the cell cycle, cyclin D1 together with its cyclin dependent
      kinase (cdk) partner, is responsible for transition to the S (DNA synthesis)
      phase by phosphorylating the product of the retinoblastoma gene (pRB), which then
      releases transcription factors important in the initiation of DNA replication.
      Amplification of the CCND1 gene or overexpression of the cyclin D1 protein
      releases a cell from its normal controls and causes transformation to a malignant
      phenotype. Analysis of these changes provides important diagnostic information in
      mantle cell (and related) lymphomas, and is of prognostic value in many cancers.
      Knowledge of cyclin D1's role in malignancy at the various sites, provides a
      basis on which future treatment directed against this molecule can proceed.

PMID- 9624415
TI  - Imprinted H19 oncofetal RNA is a candidate tumour marker for hepatocellular
      carcinoma.
AB  - AIMS/BACKGROUND: To study the expression of the H19 gene in hepatocellular
      carcinoma. H19 is an imprinted, maternally expressed gene, which is tightly
      linked, both physically and functionally, to the paternally expressed insulin
      like growth factor 2 (IGF II). IGF II is known to be involved in liver
      carcinogenesis. H19 was first discovered in the fetal mouse liver to be under the
      same regulatory genes as alpha fetoprotein (alpha FP), a widely used tumour
      marker for hepatocellular carcinoma. METHODS: Using both radioactive and non
      radioactive in situ hybridisation, the expression of the H19 gene was compared
      with the presence of alpha FP, as demonstrated by immunohistochemistry, in 18
      cases of hepatocellular carcinoma. RESULTS: H19 expression was present in 13 of
      18 cases, whereas staining for alpha FP was positive in only nine of 18 cases.
      Concordance was found in 12 of 18 tumours (66.7%). In general, the staining
      pattern for H19 was more diffuse than the immunohistochemical staining for alpha
      FP. CONCLUSIONS: The addition of a non-radioactive in situ hybridisation assay
      for H19 RNA to the panel of tumour markers used for the histopathological and
      cytological diagnosis of hepatocellular carcinoma might be useful.

PMID- 9624416
TI  - Expression of mdm2 and p53 in epithelial neoplasms of the colorectum.
AB  - AIMS: To evaluate the respective roles of mdm2 (murine double minute 2) and p53
      in the development of colorectal carcinoma. METHODS: Formalin fixed, paraffin wax
      embedded tissues from 72 sporadic adenomas and 55 carcinomas were investigated by
      means of immunohistochemistry for mdm2 and p53. RESULTS: mdm2 was expressed
      weakly in 17 of 72 (23.6%) adenomas and in 14 of 55 (25.4%) carcinomas. p53 was
      expressed in 19 of 72 (26.4%) adenomas and in 23 of 55 (41.8%) carcinomas. Four
      adenomas and five carcinomas showed positive staining for both proteins.
      Overexpression of p53 in adenomas was associated with moderate and severe
      dysplasia but not with tumour size. No associations were found between the
      expression of mdm2 and either the degree of dysplasia or tumour size. In
      carcinomas, neither the expression of p53 nor mdm2 correlated with Dukes's stage,
      metastasis, or differentiation. No associations were found between the expression
      of p53 and mdm2 in either adenomas or carcinomas. CONCLUSIONS: Although mdm2 has
      been reported to be an oncogene, it does not appear to play a major role in the
      development of colorectal carcinoma.

PMID- 9624417
TI  - Correlation of cyclin D1 and Rb gene expression with apoptosis in invasive breast
      cancer.
AB  - BACKGROUND: In vitro studies have shown that amplification and overexpression of
      the cyclin D1 gene can accelerate the progress of cells through the G1 phase.
      Therefore, cyclin D1 may have an apoptosis inhibiting effect. The retinoblastoma
      (Rb) gene was shown recently to be an important regulator of apoptosis. AIMS: To
      evaluate whether expression of the cyclin D1 and Rb genes correlated with
      apoptotic counts in a group of 97 invasive breast cancers. METHODS: Expression of
      the cyclin D1 and Rb genes was detected by standard immunnohistochemistry using
      paraffin wax embedded sections. Apoptotic cells were counted according to a
      strict protocol, in 10 fields of vision systematically spread over the most
      poorly differentiated area of the tumour, at a magnification of x630. Apoptotic
      cells counts were expressed as apoptotic cells/mm2. RESULTS: Cyclin D1
      overexpression was found in 49% of cases. Loss of Rb expression was found in 44%
      of cases, and occurred particularly in poorly differentiated tumours. Cyclin D1
      and Rb expression showed a positive correlation (p = 0.003). Apoptotic counts
      varied from 1 to 62/mm2. There were no significant correlations between cyclin D1
      overexpression and apoptotic counts in the total group or in the retinoblastoma
      protein (pRb) positive tumours. Loss of Rb expression also showed no correlation
      with apoptotic counts. CONCLUSIONS: Cyclin D1 is frequently overexpressed in pRb
      positive tumours, but no evidence has been found for an anti-apoptotic effect of
      cyclin D1 overexpression or Rb expression in invasive breast cancer.

PMID- 9624418
TI  - Allelic imbalance and microsatellite instability of the DCC gene in colorectal
      cancer in patients under the age of 35 using fluorescent DNA technology.
AB  - AIM: To assess allelic imbalance and microsatellite instability in the region of
      the "deleted in colorectal cancer" (DCC) gene on chromosome 18q using fluorescent
      DNA technology in colorectal cancer in patients under the age of 35. METHODS:
      Thirty two cases of colorectal cancer in patients under the age of 35 and with no
      family history of colon cancer were retrieved. DNA was extracted by standard
      methods, polymerase chain reaction (PCR) was performed using Cy5 labelled primers
      to microsatellite markers (D18S21, D18S34, and D18S58) in the DCC gene. The
      results were analysed using software attached to an automated DNA sequencer.
      RESULTS: The patients ranged in age from 17 to 35 years. Nineteen were women, all
      had left sided tumours (tumours distal to the splenic flexure). Twenty eight
      cases were either stage C or D (using the Astler Coller system). The
      informativity of the three markers were as follows: D18S21, 25 of 32 (78.1%);
      D18S34, 18 of 32 (56.25%); D18S58, 24 of 32 (75%). Allelic imbalance for the
      markers, after excluding homozygous and microsatellite instability cases, was:
      D18S21, 31.8%; D18S34, 11.7%; and D18S58, 0%. Nine cases showed allelic imbalance
      for both D18S21 and D18S34, yielding a combined allelic imbalance frequency of
      39.1%. Ten cases showed microsatellite instability in at least one marker, with
      microsatellite instability seen most commonly for D18S58. Three cases showed
      microsatellite instability for all three markers. CONCLUSIONS: Approximately 39%
      of cases showed allelic imbalance for D18S21 and D18S34 markers, while
      microsatellite instability was found in 31.25% of cases. This figure is higher
      than that encountered in sporadic colorectal cancer over the age of 50,
      suggesting a role for the DNA repair genes in the pathogenesis of these cancers
      occurring under the age of 35.

PMID- 9624419
TI  - Age related decrease of NOR activity in bone marrow metaphase chromosomes from
      healthy individuals.
AB  - AIMS: To present data obtained from human bone marrow preparations from healthy
      individual showing that the proportion of metaphases with silver stained
      nucleolar organiser region (AgNOR) chromosomes is associated with the age of the
      donor. METHODS: Bone marrow preparations from eight Russian and 10 Argentinian
      healthy individuals donating bone marrow for heterologous transplantation were
      studied by silver staining. The Russian bone marrow preparations were used
      directly, while the bone marrow specimens from Argentinian donors were incubated
      for 24 hours at 37 degrees C in F-10 medium with 15% fetal bovine serum. The
      slides were silver stained by the one step method of Howell and Black with slight
      modifications. Thirty metaphases with clearly defined D and G group chromosomes
      were scored for the numbers of AgNORs. All metaphases that were adjacent to
      silver stained interphase nuclei were analysed to assess the percentage of AgNOR
      positive mitoses. The Kruskal Wallis test and Kendall's rank correlation
      coefficient (rK) were used to assess the relation between age and the percentage
      of AgNOR positive cells. RESULTS: The mean numbers (SE) of AgNORs per metaphase
      were 5.06 (0.17) and 5.56 (0.23) for the Russian and Argentinian groups,
      respectively, with no significant differences between the two groups. The common
      percentage of AgNOR positive cells decreased significantly as a function of age,
      with an rK = -0.57 (p < 0.0012). CONCLUSIONS: The percentages of AgNOR negative
      metaphases in bone marrow from healthy individuals is strongly associated with
      age and this may be related to age related telomere loss.

PMID- 9624420
TI  - Expression of the insulin-like growth factor II gene in polychlorinated biphenyl
      exposed female mink (Mustela vison) and their fetuses.
AB  - AIM: To study how polychlorinated biphenyls (PCBs) affect fetal growth and the
      expression of the insulin-like growth factor (IGF II) gene in the mink (Mustela
      vision). METHODS: Ten female mink were each exposed to 0.65 or 1.3 mg Clophen
      A50/day, respectively, during the reproductive season. The numbers and sizes of
      viable fetuses were recorded. The expression of the IGF II gene was studied by
      northern blotting using a mink specific IGF II cDNA probe. RESULTS: The number of
      viable fetuses decreased after PCB exposure in a dose dependent fashion.
      Expression of the IGF II gene in adult livers from PCB exposed animals was
      decreased, compared with control animals, in a dose dependent fashion. In
      contrast, IGF II expression in placentas and fetuses was unaltered. Furthermore,
      the maternal excretion of urinary cortisol increased in both exposed groups
      during the implantation period. CONCLUSIONS: Expression of the IGF II gene is
      downregulated by PCB exposure in the adult liver. There is also an indication
      that the regulation of the expression of this gene differs between adult and
      fetal life.

PMID- 9624421
TI  - A spin cartridge system for DNA extraction from paraffin wax embedded tissues.
AB  - A simple and efficient method of DNA extraction from paraffin wax embedded
      tissues using a spin cartridge system is described. Such DNAs were shown to be
      suitable for amplification by the polymerase chain reaction, which targeted two
      human papillomavirus genes and one globin fragment giving rise to products of
      450, 150, and 110 base pairs, respectively. Different human tissues, stored for
      up to 20 years, were successfully amplified, demonstrating the usefulness of this
      very simple procedure for retrospective studies.

PMID- 9624422
TI  - Monocyte chemotactic protein-1 in the inflammatory pseudotumour of the lung.
AB  - Inflammatory pseudotumour of the lung is a lesion mainly composed of histiocytes.
      Histiocyte accumulation may arise from local proliferation of migratory cells,
      from cytokine induced recruitment of monocytes from the systemic circulation, or
      both. Cell proliferation was investigated with Ki-67 immunostaining and cytokine
      production with reverse transcriptase-polymerase chain reaction in two cases of
      inflammatory pseudotumour of the lung. It was found that the two lesions were
      composed mainly of non-proliferating (Ki-67 non-binding) macrophages that stained
      positive for CD68, CD14, CD4, and mannose receptor. Both cases contained mRNA
      transcripts for monocyte chemotactic protein-1 (MCP-1), a monocyte
      chemoattractant, and for interleukin 6 (IL-6), an inducer of plasma cell
      differentiation. One of the two cases also contained mRNA transcripts for IL-8, a
      neutrophil chemoattractant. These findings are consistent with the possibility
      that accumulation of non-proliferating histiocytes induced by MCP-1 is one of the
      pathogenic events occurring in inflammatory pseudotumour of the lung.

PMID- 9624423
TI  - Phospholipid metabolism in the mammalian heart.

PMID- 9624424
TI  - Import of lipids into mitochondria.

PMID- 9624425
TI  - Calcium metabolism, osteoporosis and essential fatty acids: a review.
AB  - Essential fatty acid (EFA)-deficient animals develop severe osteoporosis coupled
      with increased renal and arterial calcification. This picture is similar to that
      seen in osteoporosis in the elderly, where the loss of bone calcium is associated
      with ectopic calcification of other tissues, particularly the arteries and the
      kidneys. Recent mortality studies indicate that the ectopic calcification may be
      considerably more dangerous than the osteoporosis itself, since the great
      majority of excess deaths in women with osteoporosis are vascular and unrelated
      to fractures or other bone abnormalities. EFAs have now been shown to increase
      calcium absorption from the gut, in part by enhancing the effects of vitamin D,
      to reduce urinary excretion of calcium, to increase calcium deposition in bone
      and improve bone strength and to enhance the synthesis of bone collagen. These
      desirable actions are associated with reduced ectopic calcification. The
      interaction between EFA and calcium metabolism deserves further investigation
      since it may offer novel approaches to osteoporosis and also to the ectopic
      calcification associated with osteoporosis which seems to be responsible for so
      many deaths.

PMID- 9624426
TI  - The role of sphingolipids in the process of signal transduction.

PMID- 9624427
TI  - Cloning of cDNAs or genes encoding enzymes of sterol biosynthesis from plants and
      other eukaryotes: heterologous expression and complementation analysis of
      mutations for functional characterization.

PMID- 9624428
TI  - Integration of local orientation in strabismic amblyopia.
AB  - In order to investigate the processes which integrate local orientation
      information in observers with strabismic amblyopia, we measured contrast
      thresholds for discriminating the global orientation of a pattern (3 "bars")
      comprised of Gabor patches. We found that in both eyes of amblyopic observers, as
      has been reported for normal observers [Saarinen, Levi & Shen (1997) Proceedings
      of the National Academy of Sciences USA, 94, 8267-8271], there is an
      approximately two-fold enhancement of contrast sensitivity when the global and
      local orientations are aligned (relative to mixed orientations), and a smaller
      enhancement when the global and local orientations are orthogonal. This
      orientation dependent enhancement occurs despite substantial losses of contrast
      sensitivity. These results suggest that the integration processes in the
      amblyopic eye that operate to enhance detection are essentially intact.

PMID- 9624429
TI  - The role of "contrast enhancement" in the detection and appearance of visual
      contours.
AB  - We test the proposition that the appearance and detection of visual contours is
      based on an increase in the perceived contrast of contour elements. First we show
      that detection of contours is quite possible in the presence of very high levels
      of variability in contrast. Second we show that inclusion in a contour does not
      induce Gabor patches to appear to be of higher contrast than patches outside of a
      contour. These results suggest that, contrary to a number of current models,
      contrast or its assumed physiological correlate (the mean firing rate of early
      cortical neurons) is not the determining information for identifying the contour.

PMID- 9624430
TI  - The primary visual system of adult lizards demonstrates that neurogenesis is not
      obligatorily linked to central nerve regeneration but may be a prerequisite for
      the restoration of maps in the brain.
AB  - Following optic nerve crush in the adult lizard Ctenophorus ornatus, most retinal
      ganglion cells regrow their axons into visual brain centres: however, the
      regenerated projections lack retinotopic order and the animals are blind via the
      experimental eye. Here we have used 3H-thymidine autoradiography to demonstrate
      that cell division is no longer taking place in the retina of normal adult
      lizards. We conclude that the optic nerve can regenerate in lizard even though
      cells are no longer being added to the retina. However, continued retinal
      neurogenesis may be linked to the ability to restore topographic maps.

PMID- 9624431
TI  - Motion detection on flashed, stationary pedestal gratings: evidence for an
      opponent-motion mechanism.
AB  - Contrast thresholds were measured for discriminating left vs right motion of a
      vertical, 1 c/deg luminance grating lasting for one cycle of motion. This test
      was presented on a 1 c/deg stationary grating (pedestal) of twice-threshold,
      flashed for the duration of the test motion. Lu and Sperling [(1995). Vision
      Research, 35, 2697-2722] argue that the visual system detects the underlying,
      first-order motion of the test and is immune to the presence of the stationary
      pedestal (and the 'feature wobble' which it induces). On the contrary, we observe
      that the stationary pedestal has large effects on motion detection at 7 and 15
      Hz, and smaller effects at 0.9-3.7 Hz, evidenced by a spatial phase dependency
      between the stationary pedestal and moving test. At 15 Hz the motion threshold
      drops as much as five-fold, with the stationary pedestal in the optimal spatial
      phase (i.e., pedestal and test spatially in phase at middle of motion), and the
      perceived direction of the test motion reverses with the pedestal in the opposite
      phase. Phase dependency was also explored using a very brief (approximately 1
      msec) static pedestal presented with the moving test. The pedestal of Lu and
      Sperling (flashed for the duration of the test) has a broad spectrum of left and
      right moving components which interact with the moving test. The pedestal effects
      can be explained by the visual system's much higher sensitivity to the difference
      of the contrast of right vs left moving components than to either component
      alone.

PMID- 9624432
TI  - Short-wave cone signal in the red-green detection mechanism.
AB  - Previous work shows that the red-green (RG) detection mechanism is highly
      sensitive, responding to equal and opposite long-wave (L) and middle-wave (M)
      cone contrast signals. This mechanism mediates red-green hue judgements under
      many conditions. We show that the RG detection mechanism also receives a weak
      input from the short-wave (S) cones that supports the L signal and equally
      opposes M. This was demonstrated with a pedestal paradigm, in which weak S cone
      flicker facilitates discrimination and detection of red-green flicker. Also, a
      near-threshold +S cone flash facilitates detection of red flashes and inhibits
      green flashes, and a near-threshold -S cone flash facilitates detection of green
      flashes and inhibits red flashes. The S contrast weight in RG is small relative
      to the L and M contrast weights. However, a comparison of our results with other
      studies suggests that the strength of the absolute S cone contrast contribution
      to the RG detection mechanism is 1/4 to 1/3 the strength of the S contribution to
      the blue-yellow (BY) detection mechanism. Thus, the S weight in RG is a
      significant fraction of the S weight in BY. This has important implications for
      the 'cardinal' color mechanisms, for it predicts that for detection or
      discrimination, the mechanisms limiting performance do not lie on orthogonal M-L
      and S axes within the equiluminant color plane.

PMID- 9624433
TI  - Orientation masks 3-Gabor alignment performance.
AB  - Several workers have concluded that Gabor alignment tasks are performed by using
      central tendencies of the micropatterns as a cue. One reason for this conclusion
      was that the 3-Gabor alignment task is performed equally well whether the
      orientations of the patches are collinear or orthogonal to the group orientation.
      We wished to find out if the orientation of the micropatterns has any effect on
      performance. We tested subjects in 3-micropattern alignment tasks using a variety
      of orientational conditions. If three vertically-aligned Gabor patches were
      vertical, horizontal or both, or if bullseye or Gaussian blobs were used, no
      difference in performance was found. If, however, the orientation of the patches
      was randomized, performance became much worse. Similarly, if the three patches
      were at 45 deg, thresholds were raised. The effect of orientation was maintained
      across different spatial frequencies. Control conditions involving randomization
      of the phase of the sinusoidal carrier, or jitter on the size of Gaussian blobs,
      confirmed that a central tendency of the micropatterns was indeed being used by
      subjects, indicating that the role of orientation in this task is that of a mask,
      rather than of a cue.

PMID- 9624434
TI  - Texture brightness filling-in.
AB  - The masking procedure by Paradiso and Nakayama (1991) (Vision Research, 31, 1221
      1236) was used to investigate brightness filling-in within textures made of line
      elements: a texture stimulus was masked by a second stimulus containing a square
      contour. When a uniform texture was presented, the texture region inside the
      masking square appeared darkened and a small number of texture elements were
      perceived with a degenerated shape, appearing as dim dots or shorter line
      elements; it is as if the line element expanded from a bright point to fill the
      entire region defined by its contour. If the texture stimulus was a texture patch
      segregating from the surrounding texture by an orientation gradient and this
      patch was inside the square mask, darkening was not as strong as in the previous
      condition, and masked line elements preserved their elongated shape. Brightness
      spreading was measured in two experiments using dichoptic presentations.
      Experiment 1 used an adjustment task and showed that the brightness of texture
      line elements spread from equiluminant borders between segregating textures.
      Experiment 2 used a matching task and demonstrated that spreading was blocked by
      segregation borders dependent on the orientation gradient between texture line
      elements. The selectivity for line orientation began 40-80 msec after texture
      onset and maximal spreading occurred at approximately 120 msec. These findings
      may indicate that two processes subserve filling-in within textures: the first
      spreads isotropically the mean stimulus luminance at an initial processing stage
      of image analysis; at a later stage, the second spreads a texture flow (both
      brightness and shape of line elements) directed along the orientation of texture
      line elements. The texture flow mechanism fills in with a texture surface the
      region bounded by segregation contours.

PMID- 9624436
TI  - Constraints on long range interactions mediating contour detection.
AB  - Contour detection may be mediated by lateral interactions between neighboring
      cortical neurons whose receptive fields have collinear axes of preferred
      orientation. This hypothesis was tested in psychophysical experiments and
      computer simulations using a contour detection task in which observers searched
      for groups of Gabor patches that followed spatially extended contour paths
      embedded in noise consisting of several hundred Gabor patches with random
      positions and orientations. The orientation-selective units in the simulated
      neural network were linked by facilitatory interconnections whose strength
      depended on the geometry (distance, curvature, change in curvature) of smooth
      curves connecting the orientation axes of units in a pairwise fashion.
      Psychophysical detection performance was much higher for contour signal groups
      that followed closed rather than open-ended paths. However, just two sudden
      changes in orientation of neighboring Gabor patch elements in closed-path
      contours reduced detection performance to the same levels obtained with open
      ended contours. These psychophysical data agreed with the results of the neural
      network simulations. Furthermore, the simulations also accounted for previous
      findings that removal of a single Gabor patch element from a closed-path contour
      group significantly degraded detection performance. We conclude that closure
      alone is not sufficient to enhance the visibility of a contour. However, if a
      closed contour meets certain geometric constraints, then lateral interactions
      based on these constraints can generate facilitation that reverberates around the
      closed path, thereby enhancing the contour's visibility.

PMID- 9624435
TI  - A global process in motion segregation.
AB  - Observers viewed sparse random dot cinematograms in which the moving dots were
      confined to eight windows. The motions in seven of the windows were consistent
      with a global flow pattern, while the direction of motion in the eighth window
      deviated from this pattern. The observer's task was to determine which of the
      eight windows contained the inconsistent motion. The task was performed on two
      types of global flow patterns: spirals, which appear rigid, and deformations,
      which appear highly non-rigid. Although these patterns produce qualitatively
      different global percepts, they are exactly matched in their local velocities and
      velocity differences. Observers were better able to locate an inconsistent motion
      in spiral patterns than in deformation patterns, indicating that they were using
      more than just local motion information to find the target. This result is taken
      as indirect support for a segregation process that involves fitting the stimulus
      with a global motion pattern and segregating motions inconsistent with this
      pattern.

PMID- 9624437
TI  - Thresholds for the identification of the direction of motion of plaid patterns
      defined by luminance or chromatic contrast.
AB  - Contrast thresholds for identification of the direction of motion were determined
      for sinusoidal gratings and plaid patterns moving in eight possible directions.
      Since plaid patterns are the sum of two component gratings, a prediction of the
      thresholds for plaids can be made by assuming that the motions of both component
      gratings are independently identified (probability summation). In agreement with
      standard two-stage models of plaid perception, our results show that for stimuli
      defined by luminance contrast, plaid direction thresholds can be predicted well
      from the component thresholds. This also holds for fast-moving isoluminant plaid
      patterns, but for slowly moving (< 4 Hz) isoluminant plaids, direction thresholds
      were substantially higher than the prediction from the components. In the latter
      case, subjects frequently were unable to identify the motion of the plaid in the
      pattern direction, even when the direction of motion of both components could be
      reliably identified. Different mechanisms might underlie the perception of
      luminance and isoluminant plaids at slow speeds.

PMID- 9624438
TI  - Contour integration in anisometropic amblyopia.
AB  - Contour integration was measured in a group of anisometropic amblyopes to test
      the idea recently put forward that positional uncertainty sets a fundamental
      limit to contour integration in amblyopia. Anisometropic amblyopia, unlike
      strabismic amblyopia, has little or no positional uncertainty once the initial
      filtering loss has been taken into account. Therefore, according to the
      explanation put forward to explain strabismic amblyopia, anisometropes should
      exhibit normal contour integration. We show that this expectation is realized for
      five of our six anisometropic amblyopes.

PMID- 9624439
TI  - Saccadic localization of random dot targets.
AB  - The targets for saccadic eye movements in natural visual scenes are spatially
      extended objects, yet saccades land at a single position within them. To
      characterize the spatial transformation that determines the saccadic goal
      position within attended objects, we studied saccadic localization of large
      patterns of random dots. Saccades landed with a high degree of precision near the
      center-of-gravity of the patterns (average error < 10%; SDs around the center-of
      gravity = 7-11% of target eccentricity). Predictions of landing position were
      improved by using a weighted center-of-gravity, in which the weight assigned to
      each dot was reduced by the presence of neighboring dots. Weighting based either
      on the eccentricity of dots or their position relative to the boundary of the
      pattern had no effect. The results can be accounted for by a spatial
      transformation in which the "local signs" of an initial array of detectors,
      weighted by the activity of each, are averaged to yield the saccadic goal. This
      model can account for accurate and precise saccadic localization of large
      targets, while preserving sensitivity to local pattern characteristics. Unlike
      models of recognition, the boundary of the object has the same status as the
      internal details.

PMID- 9624440
TI  - Visual test of Listing's law during vergence.
AB  - A simple visual test was used to measure how much Listing's plane rotates as a
      function of the vergence angle. This test measured the elevation-dependent
      torsional disparity of horizontal and vertical lines during three tasks: vergence
      on a near target, vergence through prisms that remained fixed, and through prisms
      that rotated with eye elevation. Consistent with our previous search-coil
      measurements, the results here suggest that the angle between the Listing's
      planes of the two eyes is somewhat less than the vergence angle.

PMID- 9624441
TI  - dmax for stereopsis and motion in random dot displays.
AB  - The upper displacement limit for motion was compared with the upper disparity
      limit for stereopsis using two-frame random dot kinematograms or briefly
      presented stereograms. dmax (the disparity/displacement at which subjects make
      20% errors in a forced-choice paradigm) was found to be very similar for motion
      and stereo at all dot densities, and to fall with increasing dot density (0.006%
      or two dots to 50%) according to a power law (exponent -0.2). If dmax is limited
      by the spacing of false targets, this pattern of results suggests that the
      spatial primitives in the input to the correspondence process may be derived from
      multiple spatial scales. A model using MIRAGE centroids provides a good fit to
      the data.

PMID- 9624442
TI  - Reduced retinal deficits in an albino mammal with a cone rich retina: a study of
      the ganglion cell layer at the area centralis of pigmented and albino grey
      squirrels.
AB  - In all albino mammals studied the central retina is underdeveloped and there is a
      rod deficit. Central ganglion cell density is approximately 25% below normal.
      This is not seen in birds, which have a come dominated retina. Here we examine
      the ganglion cell layer in a cone rich mammal, the squirrel Sciurus carolinensis
      leucotis. Central cell densities were only < 5% lower in the albinos than in
      pigmented squirrels. Squirrels are the only known albino mammal to survive
      successfully in the wild, reinforcing the notion that their visual deficits are
      minor. The relative immunity of these albino retinae from this deficits may be
      related to different patterns of cell production between rod and cone dominated
      eyes.

PMID- 9624443
TI  - Fetal development of the pituitary gland in the beagle.
AB  - BACKGROUND: The pituitary gland of the dog is different from all animals and is
      described as "typical" for mammals. How might this complex pituitary gland of the
      dog be formed in fetal life? The current study examined the fetal development of
      the complex and unique dog pituitary and the ontogeny of specific cell types in
      the pars distalis. METHODS: Adenohypophysis of the beagle, from 25 to 60 days of
      gestation and at 2 days of age, was studied by immunocytochemical and
      histological staining. RESULTS: At 25 days gestation, the primordium (Rathke's
      pouch) of the adenohypophysis began to form by an upward evagination from the
      epithelium of the primary oral cavity. At 38 days, the pituitary gland showed the
      same morphology as in adult dogs, being merely smaller. Five walls of Rathke's
      pouch (anterior wall [A], lateral walls [L], posterior wall [P], and upper wall
      [U] were found at 25 days, and by 38 days they had specialized into specific
      regions of the adenohypophysis through complex and unique processes. The pars
      intermedia was derived from the U and the dorsal area of the A. The pars
      tuberalis was derived from the dorsal area of the A. The pars distalis was formed
      by more singular processes: the peripheral areas of the pars distalis were first
      formed by A and P; then the ventral lumen of the extensive Rathke's lumen
      surrounded by these areas was filled up by proliferation of cells, although the
      dorsal lumen remains as Rathke's lumen after 38 days. The blood capillaries may
      play an important role in the development of parencymal cells in the Rathke's
      pouch during canine fetal life. At 30 days gestation, the first
      adrenocorticotropic hormone cells were found in the anterior- and posterior
      ventral regions (derived from middle and ventral areas of the A and the P) of the
      pars distalis anlage, and blood capillaries invaded the parenchymal cells from
      the mesencyme surrounding the anlage. At 38 days, portal vessels without
      capillary loops in the median eminence had appeared, and growth hormone and
      luteinizing hormone cells appeared in the ventral areas of A and P in the pars
      distalis. By 52 days, when capillary loops were seen in the portal vessels in the
      median eminence, these types of cells spread through the whole pars distalis.
      CONCLUSION: These areas in the epithelium of Rathke's pouch at 25 days may
      differentiate into specific regions of the pars distalis during subsequent fetal
      life, through complex processes that are characteristics to the canine species.

PMID- 9624444
TI  - Mode of migration of normal lymphocytes inside murine testis.
AB  - BACKGROUND: Previous studies have shown that in murine experimental autoimmune
      orchitis (EAO), lymphocytes preferably infiltrate into (1) the testicular capsule
      near the rete testis, (2) the subcapsular interstitium away from the rete testis,
      and (3) the interstitium surrounding the tubuli recti and rete testis. Therefore,
      these three sites might provide tissue environments in which specific lymphocytes
      can easily gain access to testicular autoantigens. However, there is another
      possibility that infiltrating lymphocytes in the testis spontaneously accumulate
      at these three sites via the lymphatic flow inside this organ during EAO.
      METHODS: To examine this possibility, normal lymphocytes were locally injected
      into the peripheral testis regions of recipient mice. Testes were then collected
      at various times for investigating the chronological pattern of lymphocytic
      migration inside the testes at a light microscopic level. RESULTS: The injected
      lymphocytes first stayed in the lymphatic space around the seminiferous tubules
      and then moved to the subcapsular lymphatic space away from the rete testis. The
      lymphocytes accumulated under the testicular capsule and then gradually
      infiltrated into the adjacent capsular tissue. In the capsule, the cells
      surrounded the arteriolae and then accumulated in the capsular tissue near the
      rete testis. Thereafter, the cells finally left the testes through the lymphatics
      running in the spermatic cords. In the course of the lymphocytic drainage, it was
      noted that the injected lymphocytes appeared not to pass through the testicular
      interstitium around the tubuli recti and rete testis. CONCLUSIONS: The regional
      distributions of the testicular lymphocytes imply that the lymphatic flow in the
      testis may somewhat influence murine EAO pathology characterized by lymphocytic
      accumulation in (1) the testicular capsule near the rete testis and (2) the
      subcapsular interstitium away from the rete testis. However, the pathology
      exhibiting lymphocytic accumulation in (3) the interstitium around the tubuli
      recti and rete testis is independent on the intratesticular lymph flow.

PMID- 9624445
TI  - Distribution of muscle spindles in a simply structured muscle: integrated total
      sensory representation.
AB  - BACKGROUND: The distribution of muscle spindles (Sps) in a small muscle of simple
      architecture, the capsularis at the cat's hip joint, was quantified to reveal the
      patterns of proprioceptive representation in the transverse and sagittal planes
      as well as to model the effect a local disturbance in muscle length would have on
      total Sp discharge. METHODS: Locations in serial cross-sections of the 32 and 38
      Sps in 2 muscles, 1 perfused with the hip joint flexed and the other extended,
      were plotted, and their patterns of integrated sensitivity calculated assuming
      that (1) the discharge rate of a Sp afferent varies linearly with change in
      length along the Sp's axis, and (2) that within a local disturbance produced by
      contraction of a motor unit (MU), lengths decrease either linearly or as the
      square of the distance from its center. RESULTS: The isomeric pattern of
      "integrated, total Sp representation on cross-section" showed two peaks of
      sensitivity in the half of the muscle that had been next to the joint capsule,
      offset by low representation in a small, central area and along the extensive
      zone bordering the laterally facing "superficial surface." The equivalent radius
      of an idealized symmetrical MU territory was estimated from distributions of the
      few fast, oxidative-glycolytic fibers found in two muscles, and the effect of a
      MU's contraction on net Sp discharge predicted when the unit was positioned at
      distinctive sites within the pattern. As an index of Ia and II afferent
      representation in the sagittal plane, the distribution of the nucleated regions
      of Sps and the summed lengths of segments of Sp axial bundles and capsules,
      respectively, within successive 1-mm segments of the muscle were graphed.
      CONCLUSIONS: The longitudinal representation and structure of the muscle are not
      suited for reflex adjustment of differences in length along the muscle. The
      isomeric pattern of high relief in the transverse plane suggests that in this
      approximately 0.2 g muscle, the localization of myotatic reflexes might be
      accommodated but the need for adjustment in activation of MUs seems minimal. This
      is because the muscle is not compartmentalized, its fibers extend between the
      muscle's origin and insertion, their angle of pinnation is low, and greater than
      90% are of slow type. The distribution of Sps is consistent with gauging length
      of the entire muscle and hence angulation at the hip joint.

PMID- 9624446
TI  - Immunohistochemical and morphometric studies of the fetal pancreas in diabetic
      pregnant rats. Effects of insulin administration.
AB  - BACKGROUND: Maternal diabetes influences fetal pancreas development. As there are
      some controversial reports, we studied the morphometric changes of the fetal
      insular pancreas and insulin immunostain of beta cells as well as the
      proliferative activity of insular cells in 21-day-old fetuses from control,
      diabetic, and insulin-treated diabetic pregnant rats. METHODS: Streptozotocin was
      injected into 7-day-pregnant rats (controls were not injected). Some rats were
      either left untreated (diabetic) or injected with insulin. Animals were killed at
      21 days of gestation. Fetal pancreas were fixed in toto for the morphometry and
      immunohistochemistry studies using anti-insulin, anti-Ki-67 and anti
      proliferating cell nuclear antigen (PCNA) antibodies. RESULTS: Diabetic status
      was determined by measuring maternal and fetal serum glucose and insulin levels.
      The morphometric studies showed hyperplasia of the diabetic fetal insular tissue
      which had not been normalized by insulin therapy. Diabetes caused an increase of
      both insulin-positive and insulin-negative cells. The increase in insulin
      positive cells was not corrected by insulin treatment, although the number of non
      beta cells became normal. The nuclear area in beta cells increased in diabetic
      rats but was not corrected by insulin. The cytoplasmic area decreased in diabetic
      rats and was normalized by insulin administration. Diabetes increased the
      expression of the nuclear antigen Ki-67 in fetal insular pancreas, and insulin
      treatment returned it to the normal state. CONCLUSIONS: Maternal diabetes leads
      to hyperstimulation of fetal beta cells, with increased proliferative activity.
      Insulin administration to the dams corrects some of the changes observed.

PMID- 9624447
TI  - Synaptoid contacts between gland cells of the anterior pituitary of the rat.
AB  - BACKGROUND: There is evidence suggesting cross-talk among gland cells of the
      anterior pituitary. We had reported a rare form of synaptoid contact between
      corticotrophs in the anterior pituitary of the dog. We then found similar
      synaptoid contacts with different characteristics in the rat, as described in the
      present article. METHODS: Male Sprague-Dawley rats were used. The anterior
      pituitaries were prepared for ultrastructural study of substance P
      immunoreactivity of the anterior pituitary. Routine preembedding
      immunohistochemical staining was conducted, the sections were embedded in Epon
      812 (Serva Feinbiochemica, Heidelberg, New York), and ultrathin sections were
      prepared. RESULTS: In the anterior pituitary of the rat, synaptoid contacts were
      found between corticotrophs and lactotrophs. They appeared very close to typical
      synapses in the central nervous system, aside from evident weakness of
      presynaptic density. CONCLUSIONS: The presence of synaptoid contacts suggests a
      form of cross-talk between the gland cells in the anterior pituitary of the rat.

PMID- 9624448
TI  - The identification and chemical coding of cholinergic neurons in the small and
      large intestine of the mouse.
AB  - BACKGROUND: The recent availability of antisera to the vesicular acetylcholine
      transporter (VAChT) and choline acetyltransferase (ChAT) that demonstrate
      peripheral cholinergic neurons has made possible the anatomical identification of
      cholinergic neurons in the enteric nervous system. In this study, we localised
      cholinergic neurons in the mouse small and large intestine and identified which
      substances are found colocalised in the cholinergic neurons. METHODS:
      Immunohistochemical single and double staining techniques were used on whole
      mount preparations and frozen sections to examine the localisation and chemical
      coding of cholinergic neurons in the small and large intestine of the mouse.
      Cholinergic neurons were identified using antisera to ChAT or VAChT. RESULTS: In
      both the small and large intestine, numerous ChAT-immunoreactive nerve cell
      bodies were present in the myenteric and submucous ganglia, and ChAT- and VAChT
      immunoreactive nerve terminals were abundant in the myenteric and submucous
      plexuses and the external muscle. Previous studies have identified two major
      classes of myenteric neurons in the small intestine of the mouse--those
      containing calretinin plus substance P, and those containing nitric oxide
      synthase (NOS) plus vasoactive intestinal peptide (VIP). Double-label studies
      showed that the vast majority of the calretinin/substance P neurons were
      cholinergic neurons, whereas only a small proportion of the NOS/VIP cells were
      cholinergic; the noncholinergic NOS/VIP neurons were motor neurons or
      interneurons, whereas the cholinergic NOS/VIP neurons appeared to be exclusively
      interneurons. In the small intestine, all of the 5-HT-loaded neurons and a
      subpopulation of the calbindin neurons were also cholinergic. In the large
      intestine, there was a pattern of overlaps similar to that found in the small
      intestine, except that in the large intestine approximately 25% of the calretinin
      cells were not cholinergic. Only approximately one third of the GABA-loaded
      neurons in the large intestine were cholinergic. CONCLUSIONS: Large
      subpopulations of motor neurons and interneurons in the mouse small intestine are
      cholinergic neurons.

PMID- 9624449
TI  - Distribution patterns of neural-crest-derived melanocyte precursor cells in the
      quail embryo.
AB  - BACKGROUND: In vertebrate embryos, migration of trunk neural crest cells (NCC)
      proceeds mainly in two streams: a dorsoventral path between the neural tube and
      somites, and a dorsolateral one between somites and ectoderm. This last pathway
      is taken by melanocyte precursor cells (MPC) homing the skin, while pigment cells
      seeding internal organs and the peritoneal wall follow the dorsoventral pathway.
      Early routes taken by subpopulations of NCC have been well documented using the
      quail-chick chimaera system and monoclonal antibodies to NCC. However, very
      little is known about the advanced migratory behavior of MPC, which determines
      their late distribution patterns at different embryonic axial levels. METHODS:
      Histological sections of neck, thorax, and abdomen of 6.5 to 9 day quail embryos
      submitted to DOPA reaction (tyrosinase activity) were used. In four concentric
      areas--dorsal and ventrally subdivided--the relative density of MPC was
      determined by morphometric methods. RESULTS: The relative regional density of MPC
      from their individualization as DOPA-positive putative pigment cells until their
      definitive seeding in the epidermis showed a progressively higher cell density
      from deeper to peripheral zones in all three levels studied, with peaks of cell
      density suggesting a centrifugal pattern occurring in at least two waves of
      migratory cells. CONCLUSIONS: The spatial distribution of the MPC varies
      according to both the axial level and the developmental stage of the embryo.
      Furthermore, the general pattern of centrifugal distribution observed might be
      attributed to a different timing of cell differentiation closely related to their
      migratory behavior.

PMID- 9624450
TI  - Vascular volume determination of articular tissues in normal and anterior
      cruciate ligament-deficient rabbit knees.
AB  - The vasculature of diarthroidal joints has been well documented; however, the
      volume of vessels supplying different articular tissues is unknown. Angiogenesis,
      the formation of new vessels from preexisting ones, is difficult to quantify in
      joints due to the unavailability of a suitable technique. Although angiogenesis
      is known to occur in rheumatoid arthritis, the development of new vessels
      following joint injury has not been ascertained. A vascular casting technique was
      developed using carmine red dye to measure the vascular volume of the medial
      collateral ligament (MCL), lateral collateral ligament (LCL), menisci, medial
      capsule, and infrapatellar fat pad of the rabbit knee joint. Vascular volume
      determinations were repeated at 4 weeks in a group of anterior cruciate ligament
      (ACL)-transected animals and in a sham-operated control group. The volume of
      vessels supplying the MCL was estimated to be 0.22 +/- 0.07 microliter (mean +/-
      S.E.M.), the LCL volume was 0.25 +/- 0.05 microliter, the medial meniscus volume
      was 0.19 +/- 0.03 microliter, the lateral meniscus volume was 0.40 +/- 0.08
      microliter, the medial capsule volume was 0.14 +/- 0.05 microliter, and the
      infrapatellar fat pad volume was 1.90 +/- 0.62 microliters. Following ACL
      transection, angiogenesis was found to occur in the MCL only. All other tissue
      vascularities were not significantly different from sham-operated controls. A
      quantifiable method for measuring vascular volume of knee joint tissues has been
      described. Joint instability stimulates angiogenesis in the ipsilateral MCL;
      however, the absence of angiogenic activity in other articular tissues might help
      explain the lack of posttraumatic healing associated with these joints.

PMID- 9624451
TI  - Scanning electron microscopy and immunohistochemical observations of the vascular
      nerve plexuses in the dental pulp of rat incisor.
AB  - BACKGROUND: The innervation of rat incisors, which are continuously erupting
      teeth, is quite unique. Although many reports have documented the neural control
      of the pulpal blood flow, only a few studies have examined the structure and
      distribution of vascular nerves in the rat incisors. This study examined the
      nerve plexuses and the spatial relationship of nerve terminals to smooth muscle
      cells of the pulp vessels of rat incisors. METHODS: The innervation of the pulp
      vessels of rat incisors was studied using immunohistochemical evaluations of
      calcitonin gene-related peptide (CGRP) and neuropeptide-Y (NPY). The three
      dimensional ultrastructure of nerve meshworks and terminals on smooth muscle
      cells of pulp arterioles were examined by scanning electron microscopy (SEM) with
      a KOH digestion method. RESULTS: The blood vessels were associated with many
      nerve fibers immunoreactive for CGRP and NPY. Some NPY and frequent CGRP
      immunoreactive nerve fibers were observed in the labial odontoblast layer. Three
      different morphologies of nerve fibers could be distinguished: fine nerve fibers
      with numerous terminal varicosities, medium-sized fibers associated with
      occasional or much scarcer varicosities, and thick fibers that had no varicosity
      and sometimes ran apart from blood vessels. The SEM observations identified five
      vascular segment types: terminal arterioles, precapillary arterioles,
      capillaries, postcapillary venules, and muscular venules. Nerve meshworks were
      observed around the large terminal arterioles; these meshworks were very
      comparable to those revealed by immunohistochemistry. The vascular smooth muscle
      cells were closely attached by one or more terminal varicosities. CONCLUSIONS: It
      has become evident that the large terminal arterioles in the rat incisors receive
      a dense nerve supply and provide well-developed wall architecture, suggesting an
      important role of neuronal regulation on the vessels.

PMID- 9624452
TI  - Innervation of the supranasal sac of the puff adder.
AB  - BACKGROUND: The supranasal sac is an invagination of the skin between the
      supranasal and nasal shields of many true vipers. Viperinae behavior suggests
      that many true vipers hunt by thermal cues. METHODS: The supranasal sacs of two
      puff adder (Serpentes: Viperinae) were examined with modern histological and
      neurohistological techniques, including Kiernan's silver stain. RESULTS: There
      are nerve endings in the supranasal sac of the puff adder that resemble the nerve
      endings in the labial pits of boas. CONCLUSION: This suggests that the supranasal
      sac of true vipers is, like the labial pits of boas, a heat detector.

PMID- 9624453
TI  - Coexistence of enkephalin- and tyrosine hydroxylase-like immunoreactivities in
      nerve fibers of the temporomandibular joint capsule of the guinea pig.
AB  - BACKGROUND: The innervation of joints has been suggested to play an important
      role for their normal function as well as for the pathogenesis of chronic
      arthritic conditions. It is therefore important to elucidate the functional
      anatomy of this innervation. METHODS: The expression of methionine enkephalin
      like immunoreactivity (ENK-LI) and tyrosine hydroxylase (TH)-LI as well as their
      possible colocalization were examined in the temporomandibular joint of the
      guinea pig: RESULTS: Nerve fibers with ENK-LI were demonstrated in the synovium
      of the guinea pig temporomandibular joint capsule with the use of indirect
      immunofluorescence. The ENK+ fibers were found close to the surface of the
      synovial membrane, deeper in the synovium, and at the walls of blood vessels.
      Coexistence of ENK- and TH-LI was observed frequently in the synovial nerve
      fibers. After removal of the superior cervical ganglion (SCG), the ENK-containing
      nerve fibers were reduced substantially in number on the operated side or were
      completely absent if the cervical sympathetic trunk was also excised.
      CONCLUSIONS: The findings indicate that the majority of fibers with ENK-LI derive
      from the SCG ENK may act as a neuromodulator on the catecholaminergic nerves and
      may also have an analgesic effect in the joint.

PMID- 9624454
TI  - Scanning electron microscopy of denervated taste buds in hamster: morphology of
      fungiform taste pores.
AB  - BACKGROUND: Taste pores of fungiform papillae are critical for taste function.
      Taste nerve injury affects the pore, rendering it refractory to staining with
      vital dyes. Whether pores of denervated fungiform papillae disappear or undergo
      more modest structural changes to account for diminished staining was the subject
      of the present study. METHODS: The chorda tympani in the hamster was served
      unilaterally and the anterior tongue prepared for scanning electron microscopy
      after 31 days of survival. RESULTS: Taste pores were found on 92% of control
      fungiform papillae. They were round openings formed by the free margins of
      keratinocytes, and centered in hillock-shaped elevations of the papillary
      surface. Hillocks were encircled by an indentation which, in turn, was surrounded
      by a circular epithelial rim. These structures associated with fungiform pores
      distinguish pores on the anterior tongue from those on the posterior tongue. The
      pores led to a channel that penetrated into the papilla. The experimental side of
      the tongue had markedly fewer pores. Definitive pores were present on only 53% of
      denervated papillae. The papillae that lacked pores either exhibited a small
      hillock and a subtle depression in place of the pore, or had entirely flat apical
      surfaces. The denervated papillae that retained pores exhibited structural
      changes. The pores had smaller diameters and led to shallower channels than
      control pores. Moreover, these persistent pores were associated with hillocks,
      indentations and rims that were more variable and less distinct than those of
      control papillae. CONCLUSIONS: Pores of fungiform papillae in hamster are
      associated with specialized surfaces features of the papillary epithelium.
      Denervation results in changes that range from disappearance of the pores to
      their shrinkage and the atrophy of pore-associated epithelial structures.

PMID- 9624455
TI  - Muscle contractility decrement and correlated morphology during the pathogenesis
      of streptozotocin-diabetic mice.
AB  - BACKGROUND: Peripheral neuropathy of both motor and sensory nerves has been well
      documented in diabetes mellitus, but the evidence for physiological and
      correlated morphological changes during the pathogenesis of myopathy is scarce.
      In the present report, we have chosen the dorsiflexor muscle of adult male mice
      as a model for studying in situ muscle contraction and neuromuscular
      ultrastructure during the pathogenesis of streptozotocin-induced diabetes.
      METHODS: Thirty mice (30 g bodyweight) were injected once i.p. with
      streptozotocin solution (200 mg/Kg) to induce experimental diabetes mellitus.
      Comparative analyses of in situ muscle isometric contractile characteristics were
      studied (at 1 Hz, 5 Hz and 30 Hz nerve stimulation) in urethane-anesthetized (2
      mg/g, i.p.) control and diabetic mice at three time points, 2 weeks, 4 weeks, and
      8 weeks postinjection. Synaptic delay was also recorded in diabetic and age
      matched control mice. RESULTS: There was a significant increase in synaptic delay
      in both 4-week and 8-week diabetic mice compared with control mice (8.9 +/- 1.2
      msec and 7.6 +/- 0.6 msec, respectively, compared with 6.1 +/- 0.5 msec). At all
      three stimulation frequencies, diabetes did not affect muscle contractile speed
      but significantly reduced the twitch tension after 8 weeks, with no changes at 2
      weeks or 4 weeks. The recorded single-twitch tension values were 2.6 +/- 0.3 g,
      2.1 +/- 0.6 g, 2.2 +/- 0.7 g, and 1.2 +/- 0.1 g for control, 2 weeks, 4 weeks,
      and 8 weeks, respectively. At 30 Hz, the recorded tension values were 4.6 +/- 1.6
      g, 3.1 +/- 1.2 g, 3.1 +/- 1.1 g, and 2.1 +/- 1.0 g for control, 2 weeks, 4 weeks,
      and 8 weeks, respectively. Ultrastructural changes in neuromuscular junctions
      were similar to those that have been described in disuse and aging. These changes
      were observed after 8 weeks and included serve loss of synaptic vesicles,
      electron-dense bodies, and myelin-like figures as well as degeneration of
      mitochondria. CONCLUSIONS: The results reveal that streptozotocin-induced
      diabetes affects presynaptically the neuromuscular junction as well as muscle
      itself. Actions at both sites may contribute to the functional alterations seen
      in muscle contractile properties and may play a role in the pathogenesis of
      diabetic neuromyopathy.

PMID- 9624456
TI  - Comparison of mitosis in binucleated and mononucleated newt cardiac myocytes.
AB  - BACKGROUND: The cultured adult newt ventricular myocyte has been shown to undergo
      mitosis and cytokinesis in a fully differentiated state. Insight into its
      proliferation and cellular changes during the repair process involves obtaining a
      better understanding of the nuclear pattern (mononucleated, binucleated, or
      multinucleated) resulting from mitotic events. Mitosis is easily observable in
      cultured newt cardiac myocytes using phase-contrast microscopy. METHODS: From
      days 8-19 in culture, the process of mitosis in mononucleated and binucleated
      newt ventricular myocytes was recorded and timed by using time-lapse video
      microscopy. Cultured cardiac myocytes were double-stained for myosin and F-actin
      by using fluorescein isothiocyanate (FITC)-labeled MF20 and rhodamine phalloidin.
      RESULTS: Mitotic, mononucleated myocytes produced mononucleated daughter cells in
      80% of the cases, whereas 20% were single, binucleated myocytes, In binucleated
      myocytes, only 32% underwent complete cytokinesis to produce two binucleated
      daughter cells, whereas 68% resulted in variably nucleated myocytes.
      Mononucleated and binucleated myocytes undergoing mitosis had similar time
      intervals for the period from nuclear breakdown (prometaphase) to the start of
      anaphase (108.7 minutes and 94.5 minutes, respectively), but the period between
      anaphase and midbody formation was significantly shorter in binucleated than in
      mononucleated myocytes (43.5 minutes and 69.3 minutes, respectively). The
      myofibrillae were not as well organized in binucleated myocytes as those observed
      in mononucleated myocytes. CONCLUSIONS: Mitosis in vitro appears to proceed more
      rapidly in binucleated newt cardiac myocytes, which have more poorly organized
      myofibrillae than mononucleated myocytes. Mitosis of cultured binucleated
      myocytes commonly results in variably nucleated daughter cells, whereas
      mononucleated myocytes produce predominantly mononucleated daughter cells.

PMID- 9624457
TI  - Role of endoplasmic reticulum-derived vesicles in the formation of Golgi elements
      in sec23 and sec18 Saccharomyces Cerevisiae mutants.
AB  - BACKGROUND: In the yeast Saccharomyces cerevisiae, the Golgi apparatus consists
      of individual networks of membranous tubules interspersed throughout the
      cytoplasm. When sec23 and sec18 mutants are shifted from the permissive (20
      degrees C) to the restrictive (37 degrees C) temperature, the secretory pathway
      is blocked between endoplasmic reticulum (ER) and Golgi elements. When examined
      with an electron microscope, sec23 displays an excess of ER membranes, whereas
      sec18 accumulates small vesicles. The present investigation describes the
      kinetics of the ultrastructural modifications of the Golgi and vesicular elements
      when sec23 and sec18 mutants are shifted for 10 min to restrictive temperature
      and then returned to permissive temperature for various time intervals. METHODS:
      S. cerevisiae sec23 and sec18 mutants from exponentially growing cultures at 20
      degrees C were maintained for 10 min at the restrictive temperature of 37 degrees
      C and returned to the permissive temperature of 20 degrees C for different time
      intervals. Following fixation in glutaraldehyde and postfixation in potassium
      ferrocyanide reduce osmium, 80- to 200-nm-thick sections were prepared from Epon
      embedded yeast cells. Using the thicker sections, stereopairs of electron
      microscopy photographs were prepared and used to visualize the three-dimensional
      configuration of the organelles. To follow the modifications of cell organelles,
      cell sections were selected at random in thinner sections and cell organelles
      were scored. RESULTS: At permissive temperature (20 degrees C), the Golgi
      apparatus consisted of individual networks of tubules dispersed in the cytoplasm,
      as in the wild type strain. When both mutants were shifted for 10 min at the
      restrictive temperature (37 degrees C), the main structural feature was the
      disappearance of all Golgi networks. In sec23 mutant cells, there was an increase
      in number of tubular, nonnodular networks corresponding to terminal portions of
      the endoplasmic reticulum; in sec18 cells, small 20- to 50-nm tubules and
      vesicles accumulated in the cytoplasm. Within minutes after the return of sec23
      cells to permissive temperature (20 degrees C), small vesicles and tubules
      started to accumulate to reach a number similar or greater than that noted in
      sec18 cells observed under the same conditions. At later time intervals and in
      both mutants, the small tubules and vesicles decreased in number. This decrease
      was concomitant with the reappearance of fine nodular networks, followed later on
      by the reconstruction of networks of larger caliber and the formation of
      secretion granules. CONCLUSIONS: It is concluded that a block of the secretory
      pathway upstream of the Golgi compartment leads to the disappearance of Golgi
      networks. The small vesicles and tubules that accumulate during the block in
      sec18 cells and within minutes after the shift at 20 degrees C in sec23 cells
      appear to fuse together to form new Golgi networks. Thus, the small vesicles
      would not fuse with a preexisting Golgi apparatus but would rather fuse together
      to produce new Golgi networks. Such networks appear as transitory structures
      continuously undergoing renewal.

PMID- 9624458
TI  - Comparison of bone loss during normal lactation with estrogen deficiency
      osteopenia and immobilization osteopenia in the rat.
AB  - BACKGROUND: Substantial changes in mineral and skeletal metabolism occur during
      pregnancy and lactation. The purpose of this study was to compare three
      contrasting osteopenic states in the rat: (1) physiological (lactation), (2)
      endocrine-deficiency (ovariectomy), and (3) lack of mechanical usage
      (immobilization). METHODS: One group of female rats went through a pregnancy and
      21 days of lactation (LAC). Another group was ovariectomized (OVX) for 6 weeks,
      and another group had one hind limb immobilized (IMM) for 6 weeks. Bone mineral
      density was determined by photon absorptiometry, and changes in cancellous and
      cortical bone were determined by backscattered electron imaging (BSE), scanning
      electron microscopy (SEM), structural morphometry, and fluorochrome-based
      histomorphometry. RESULTS: The LAC group gained the most weight but had the least
      bone mineral density and metaphyseal bone mass. The OVX and IMM groups also had
      less bone mass than controls (CONT). Changes in cancellous bone structure
      occurred in all groups, but the IMM group had a more uniform distribution of
      metaphyseal bone loss. Longitudinal bone growth was greater in the IMM and OVX
      groups but less in the LAC group. Cancellous bone formation rates were greater in
      the OVX and LAC group. Cortical bone width was less in the LAC, IMM, and OVX
      groups. Periosteal bone formation was greater in the OVX group but less in the
      LAC group. CONCLUSIONS: Considerable osteopenic changes occur in cancellous and
      cortical bone during the first reproductive cycle in the rat. The osteopenia of
      lactation is somewhat similar to that observed after ovariectomy, likely because
      both are hypoestrogenic conditions. Because this bone loss occurs during a normal
      physiological event, these data suggest that before the first reproductive cycle,
      the female rat has a skeletal mass in excess of that needed for normal mechanical
      usage.

PMID- 9624459
TI  - Wrinkles induced by the use of smoothing procedures applied to serial growth
      data.
AB  - This paper elucidates the effects of moving average filters when applied to
      serial growth measurements. This is a question of interest because smoothing
      procedures are inherently part of a number of analytical methods presently
      employed in auxological analyses. Particular attention is paid to sequential
      growth data analysed to identify what has been described as pulsatile, saltation
      and stasis patterns or mini-growth spurts. When applied to pulsatile, or
      saltatory, time series data the process of smoothing itself creates artifactual
      temporal patterns in the time series data similar to previously described mini
      growth spurts while removing the actual pulsatile characteristics of the data.
      These observations illustrate that smoothing approaches add noise to time series
      data while removing meaningful patterns in the original data sequence. Analyses
      employing such approaches produce results that include waveforms or other
      fluctuations compatible with an underlying pulsatile driving mechanism, but do
      not necessarily reflect the temporal characteristics of the original biological
      process.

PMID- 9624460
TI  - An example of variation and pattern in saltation and stasis growth dynamics.
AB  - The serial data from two siblings, aged 6.6 and 7.5 years of age at the
      initiation of the study, measured each evening for total standing height during
      365 days, are analysed by two methods to investigate the nature of the underlying
      growth pattern. The saltation and stasis model, designed to identify the presence
      of statistically significant pulses in sequential data, is compared for goodness
      of-fit to first to sixth degree polynomial functions, used to investigate the
      presence of a slowly varying smooth continuous function in the data, and high
      order polynomials of the same degree of flexibility as the individual's saltation
      and stasis results. The saltation and stasis model is found to better-fit the
      experimental data than the slowly varying smooth continuous functions (p < 0.01
      to 0.001). The timing characteristics of the saltation and stasis patterns are
      investigated and the temporal patterns are suggestive of a non-random,
      aperiodical deterministic system.

PMID- 9624461
TI  - Genetics of human body size and shape: pleiotropic and independent genetic
      determinants of adiposity.
AB  - The present study utilized pedigree data from three ethnically different
      populations of Kirghizstan, Turkmenia and Chuvasha. Principal component analysis
      was performed on a matrix of genetic correlations between 22 measures of
      adiposity, including skinfolds, circumferences and indices. Findings are
      summarized as follows: (1) All three genetic matrices were not positive definite
      and the first four factors retained even after exclusion RG > or = 1.0, explained
      from 88% to 97% of the total additive genetic variation in the 22 trials studied.
      This clearly emphasizes the massive involvement of pleiotropic gene effects in
      the variability of adiposity traits. (2) Despite the quite natural differences in
      pairwise correlations between the adiposity traits in the three ethnically
      different samples under study, factor analysis revealed a common basic pattern of
      covariability for the adiposity traits. In each of the three samples, four
      genetic factors were retained, namely, the amount of subcutaneous fat, the total
      body obesity, the pattern of distribution of subcutaneous fat and the central
      adiposity distribution. (3) Genetic correlations between the retained four
      factors were virtually non-existent, suggesting that several independent genetic
      sources may be governing the variation of adiposity traits. (4) Variance
      decomposition analysis on the obtained genetic factors leaves no doubt regarding
      the substantial familial and (most probably genetic) effects on variation of each
      factor in each studied population. The similarity of results in the three
      different samples indicates that the findings may be deemed valid and reliable
      descriptions of the genetic variation and covariation pattern of adiposity traits
      in the human species.

PMID- 9624462
TI  - Growth charts for Iran.
AB  - Growth charts for children aged 2-18 years old in Iran are presented. The charts
      are based on a random cluster sample survey of 3301 children living in urban
      Tehran, whose heights and weights were measured during the 1990-1992 National
      Health Survey of Iran. Because of differences between the data from the different
      provinces, these data were used as a representative subset of the total data.
      Charts were constructed using Healy's method, as modified by Pan, Goldstein and
      Yang, and are shown to fit the data well. Simulations show that the structure of
      the data does not affect the centile estimates. These charts may be used for all
      urban children in Iran and modifications are suggested to enable them to be used
      for rural children, who are generally smaller than urban children.

PMID- 9624463
TI  - Growth of children in Iran.
AB  - Weights and Heights of 22,349 children and adolescents aged 2 to 18 in Iran are
      reported. Data are from the 1990-1992 National Health Survey, a random cluster
      sample survey of 1 in 1000 families in all provinces of Iran. Multilevel models
      (Goldstein 1995) which take account of the survey design, reveal significant
      differences between provinces and between urban and rural children. Differences
      between urban and rural children, like differences between girls and boys,
      persist across all provinces and are certainly real. Differences between
      provinces may be partly due to differences in calibration. Charts based on the
      homogeneous subset of children living in urban Tehran may be used for all urban
      children, and in modified form, for all rural children. All the centiles of these
      charts are substantially below those of the NCHS charts, but the spread is
      similar so that there is no suggestion that the difference is due to the
      prevalence of gross malnutrition. The difference shows that the use of locally
      based growth charts are essential for assessing the growth of children in Iran.

PMID- 9624464
TI  - An examination of the definition 'final height' for practical use.
AB  - Determining which of various 'final height' definitions is most applicable to the
      data sets is a useful preceding step for studies concerning adult stature
      prediction. This paper presents an examination of three definitions and their
      validity when practically applied to two different longitudinal data sets. Two
      data series examined in this study are T-data (31 boys and 35 girls born between
      1967 and 1978) and H-data (113 girls born between 1956 and 1966). Three
      definitions of final height applied to the data are: (1) Final stature at 18
      years of age (Fht (18)); (2) Stature after a year with an annual increment less
      than 0.5 cm (Fht (0.5)); and (3) The highest measurement (Fht (hst)). The results
      of this study suggest the greatest height of an individual measurement (Fht
      (hst)) is the most effective definition of 'final stature' for practical use.
      This definition can be applied to various types of data, whether measurements are
      obtained from individuals during school periods, or whether measurements are
      obtained from individuals until the cessation of growth.

PMID- 9624466
TI  - Phase I safety and pharmacokinetics study of micronized atovaquone in human
      immunodeficiency virus-infected infants and children. Pediatric AIDS Clinical
      Trials Group.
AB  - A phase I dose-escalating safety and pharmacokinetic study evaluated an oral
      suspension of micronized atovaquone (m-atovaquone) in infants and children
      stratified into age groups from 1 month to 12 years of age. Dosages of 10, 30,
      and 45 mg/kg of body weight/day were evaluated as single daily doses over a
      period of 12 days. Steady-state concentrations in plasma were determined on day
      12, and single postdose concentrations were measured on days 1, 3, 5, 7, 9, 13,
      15, 18, 21, and 24. Prior studies with adults suggest that the average plasma
      atovaquone concentration of 15 micrograms/ml is associated with therapeutic
      success in more than 95% of patients with Pneumocystis carinii pneumonitis. The
      results showed m-atovaquone to be safe and well tolerated. Dosages of 30
      mg/kg/day were adequate to achieve an average steady-state concentration of
      greater than 15 micrograms/ml in children ages 1 to 3 months and 2 to 12 years,
      but a dosage of 45 mg/kg/day was needed to reach this concentration in infants 3
      to 24 months of age. The oral suspension of atovaquone is safe and well tolerated
      in children. A single daily dose of 30 mg/kg provides bioavailability considered
      adequate for therapy of P. carinii pneumonia, but infants between 3 and 24 months
      of age may require a dosage of 45 mg/kg/day.

PMID- 9624465
TI  - Treatment of infection due to Pneumocystis carinii.

PMID- 9624467
TI  - Minocycline and cefotaxime in the treatment of experimental murine Vibrio
      vulnificus infection.
AB  - We conducted an in vivo study with the mouse model of Vibrio vulnificus infection
      to evaluate the efficacies of therapy with minocycline or cefotaxime alone and in
      combination. V. vulnificus was introduced subcutaneously into the area over the
      right thigh. The inoculum size ranged from 1.0 x 10(3) to 1.2 x 10(8) CFU from
      experiment to experiment but was constant for all animals in the same experiment.
      Antibiotics were given intraperitoneally 2 h after the bacteria were inoculated.
      In experiments 1 to 4, the standard dose for humans was used to treat the
      infection, while in experiment 5, five times the standard dose for humans was
      used to treat the infection. In experiment 1, with a small inoculum of 5 x 10(3)
      CFU, all mice in the saline-treated control group and the cefotaxime-,
      minocycline-, and combined antibiotic-treated groups survived. In experiment 2,
      with a moderate inoculum of 1.2 x 10(5) CFU, all the mice in the three antibiotic
      treated groups survived, while only two of nine mice in the control group
      survived. In experiment 3, with a large inoculum of 8.0 x 10(7) CFU, six of nine
      mice in the combined antibiotic-treated group survived, while only one of nine
      mice in the cefotaxime-treated group and none of the mice in the control and
      minocycline-treated groups survived. In experiment 4, with a large inoculum of
      1.2 x 10(8) CFU, 8 of 20 mice in the combined antibiotic-treated group survived,
      while none of the 20 mice in the control group, the group treated with cefotaxime
      alone, and the group treated with minocycline alone survived. In experiment 5, in
      which mice were infected with a large inoculum of 6.6 x 10(7) CFU and treated
      with five times the standard human dose of antibiotics, 10 of 12 mice in the
      combined antibiotic-treated group survived, while only 4 of 12 mice in the
      minocycline-treated group, 1 of 12 mice in the cefotaxime-treated group, and none
      of the mice in the control group survived. In experiments 3 to 5, the difference
      in the survival rates between the combined antibiotic-treated and minocycline
      treated groups was statistically significant (P < 0.05). These results indicate
      that combination therapy with cefotaxime and minocycline is distinctly more
      advantageous than therapy with the single antibiotic regimen for the treatment of
      severe experimental V. vulnificus infections.

PMID- 9624468
TI  - Phenotypic study of resistance of beta-lactamase-inhibitor-resistant TEM enzymes
      which differ by naturally occurring variations and by site-directed substitution
      at Asp276.
AB  - At this time an amino acid substitution at position 276 in the TEM-1 enzyme is
      associated with an additional substitution at position 69 in natural beta
      lactamase-inhibitor-resistant (IRT) beta-lactamases. The effect of the Asn276-
      >Asp substitution on resistance was assessed with the Asn276Asp variant,
      generated by site-directed mutagenesis. The mutant was resistant to beta
      lactamase inhibitors, but the MICs of amoxicillin combined with clavulanic acid
      or tazobactam were strikingly different for E. coli strains producing the
      Asn276Asp variant and those producing naturally occurring IRTs with single or
      double substitutions. The inhibitory effects of clavulanic acid and tazobactam
      were the same in IRTs with substitutions at position 69 (IRT-5 and IRT-6). The
      effect of clavulanic acid on the MICs of amoxicillin for the Asn276Asp variant
      was greater than that of tazobactam. In IRTs with double substitutions, at
      positions 69 plus 276 (IRT-4, IRT-7, and IRT-8) or 69 plus 275 (IRT-14),
      tazobactam was a more potent inhibitor than clavulanic acid. The effect of the
      Asn276-->Asp substitution on the values of the kinetic constants and the
      concentration required to inhibit by 50% the hydrolysis of benzylpenicillin
      confirms that this single mutation is responsible for resistance to beta
      lactamase inhibitors. Molecular modeling of the Asn276Asp mutant shows that
      Asp276 can form two salt bonds with Arg244 close to the penicillin-binding
      cavity. The addition of the Asp276 mutation to that preexisting at position 69
      confers a higher selective advantage to bacteria, as shown by the reduction in
      beta-lactamase inhibitor efficiencies of the double variants. Therefore, the
      emergence of multiple mutations in TEM beta-lactamases by virtue of the use of
      beta-lactamase inhibitors increases selection pressure resulting in the
      convergent evolution of resistant strains.

PMID- 9624469
TI  - Alterations in PBP 1A essential-for high-level penicillin resistance in
      Streptococcus pneumoniae.
AB  - High-level penicillin resistance in pneumococci is due to alterations in
      penicillin-binding proteins (PBPs) 2X, 2B, and 1A. We have sequenced the
      penicillin-binding domain of PBP 1A from penicillin-resistant South African
      pneumococcal isolates and have identified amino acid substitutions which are
      common to all the resistant isolates analyzed. Site-directed mutagenesis was then
      used to determine whether particular amino acid substitutions at specific
      positions in PBP 1A mediate penicillin resistance. PCR was used to isolate PBP
      2X, 2B, and 1A genes from clinical isolate 8303 (penicillin MIC, 4
      micrograms/ml). These wild-type PBP genes were cloned into pGEM-3Zf and were used
      as the transforming DNA. Susceptible strain R6 (MIC, 0.015 microgram/ml) was
      first transformed with PBP 2X and 2B DNA, resulting in PBP 2X/2B-R6 transformants
      for which MICs were 0.25 microgram/ml. When further transformed with PBP 1A DNA,
      2X/2B/1A-R6 transformants for which MICs were 1.5 micrograms/ml were obtained.
      Site-directed mutagenesis of the PBP 1A gene from isolate 8303 was then used to
      reverse particular amino acid substitutions, followed by transformation of PBP
      2X/2B-R6 transformants with the mutagenized PBP 1A DNA. For PBP 2X/2B/1A-R6
      transformants, the introduction of the reversal of Thr-371 by Ser or Ala in PBP
      1A decreased the MIC from 1.5 to 0.5 micrograms/ml, whereas the reversal of four
      consecutive amino acid substitutions (Thr-574 by Asn, Ser-575 by Thr, Gln-576 by
      Gly, and Phe-577 by Tyr) decreased the MIC from 1.5 to 0.375 micrograms/ml. These
      data reveal that amino acid residue 371 and residues 574 to 577 of PBP 1A are
      important positions in PBP 1A with respect to the interaction with penicillin and
      the development of resistance.

PMID- 9624470
TI  - Effect of metronidazole resistance on bacterial eradication of Helicobacter
      pylori in infected children.
AB  - A prospective study was performed with 23 Helicobacter pylori-infected children
      (mean age, 9.5 +/- 4.4 years) with clinical symptoms of gastritis and positive
      results of culture and histologic examination of gastric biopsy specimens to
      evaluate the influence of antibiotic resistance on eradication. Positive children
      were treated for 4 weeks with lansoprazole and for 2 weeks with either
      amoxicillin-metronidazole or spiramycin (a macrolide)-metronidazole. At endoscopy
      1 month after the discontinuation of therapy, the eradication rate and
      improvement of histologically related gastritis were significantly dependent on
      the susceptibility or the resistance of the infecting organism to metronidazole
      (83 versus 17% and 88 versus 16.6%, respectively). Pretreatment determination of
      the susceptibility is appropriate in any anti-H, pylori regimen, including one
      with metronidazole.

PMID- 9624471
TI  - Pregnancy outcome following gestational exposure to fluoroquinolones: a
      multicenter prospective controlled study.
AB  - Concerns regarding the teratogenicity of fluoroquinolones have resulted in their
      restricted use during gestation. This is despite an increasing need for their use
      due to emerging bacterial resistance. The objectives of the present investigation
      were to evaluate pregnancy and fetal outcomes following maternal exposure to
      fluoroquinolones and to examine whether in utero exposure to quinolones is
      associated with clinically significant musculoskeletal dysfunctions. We
      prospectively enrolled and followed up 200 women exposed to fluoroquinolones
      (norfloxacin, ciprofloxacin, ofloxacin) during gestation. Pregnancy outcome was
      compared with that for 200 controls matched for age and for smoking and alcohol
      consumption habits. Controls were exposed to nonteratogenic, nonembryotoxic
      antimicrobial agents matched by indication, duration of therapy (+/- 3 days), and
      trimester of exposure. Rates of major congenital malformations did not differ
      between the group exposed to quinolones in the first trimester (2.2%) and the
      control group (2.6%) (relative risk, 0.85; 95% confidence interval, 0.21 to
      3.49). Women treated with quinolones had a tendency for an increased rate of
      therapeutic abortions compared with the rate among women exposed to nonteratogens
      (relative risk, 4.50; 95% confidence interval, 0.98 to 20.57), resulting in lower
      live-birth rates (86 versus 94%; P = 0.02). The rates of spontaneous abortions,
      fetal distress, and prematurity and the birth weight did not differ between the
      groups. Gross motor developmental milestone achievements did not differ between
      the children of the mothers in the two groups. We concluded that the use of
      fluoroquinolones during embryogenesis is not associated with an increased risk of
      major malformations. There were no clinically significant musculoskeletal
      dysfunctions in children exposed to fluoroquinolones in utero. The higher rate of
      therapeutic abortions observed in quinolone-exposed women compared to that for
      their controls may be secondary to the misperception of a major risk related to
      quinolone use during pregnancy.

PMID- 9624472
TI  - S-1153 inhibits replication of known drug-resistant strains of human
      immunodeficiency virus type 1.
AB  - S-1153 is a new imidazole compound that inhibits human immunodeficiency virus
      (HIV) type 1 (HIV-1) replication by acting as a nonnucleoside reverse
      transcriptase inhibitor (NNRTI). This compound inhibits replication of HIV-1
      strains that are resistant to nucleoside and nonnucleoside reverse transcriptase
      inhibitors. S-1153 has a 50% effective concentration in the range of 0.3 to 7
      ng/ml for strains with single amino acid substitutions that cause NNRTI
      resistance, including the Y181C mutant, and also has potent activity against
      clinical isolates. The emergence of S-1153-resistant variants is slower than that
      for nevirapine, and S-1153-resistant variants contained at least two amino acid
      substitutions, including F227L or L234I. S-1153-resistant variants are still
      sensitive to the nucleoside reverse transcriptase inhibitors zidovudine (AZT) and
      lamivudine. In a mouse and MT-4 (human T-cell line) in vivo HIV replication
      model, S-1153 and AZT administered orally showed a marked synergy for the
      inhibition of HIV-1 replication. S-1153 shows a significant accumulation in lymph
      nodes, where most HIV-1 infection is thought to occur. S-1153 may be an
      appropriate candidate for two-to three-drug combination therapy for HIV
      infection.

PMID- 9624473
TI  - Randomized trial of trimethoprim-sulfamethoxazole versus pyrimethamine
      sulfadiazine for therapy of toxoplasmic encephalitis in patients with AIDS.
      Italian Collaborative Study Group.
AB  - The aim of the present pilot study was to compare the efficacy and safety of
      trimethoprim (TMP) and sulfamethoxazole (SMX) with those of the standard therapy
      pyrimethamine (P)-sulfadiazine (S) for the treatment of toxoplasmic encephalitis
      in patients with AIDS. This was a pilot, multicenter, randomized, and prospective
      study. Patients were randomly assigned to receive TMP (10 mg/kg of body
      weight/day) and SMX (50 mg/kg/day) or P (50 mg daily) and S (60 mg/kg/day) as
      acute therapy (for 4 weeks) and then as maintenance therapy for 3 months at half
      of the original dosage. Seventy-seven patients were enrolled and randomized to
      the study: 40 patients were treated with TMP-SMX and 37 were treated with P-S.
      There was no statistically significant difference in clinical efficacy during
      acute therapy. In contrast, patients randomized to TMP-SMX appeared more likely
      to achieve a complete radiologic response after acute therapy. Adverse reactions
      were significantly more frequent in patients treated with P-S, and skin rash was
      the most common adverse event noted in these patients. In conclusion, the results
      of the study suggest that TMP-SMX appears to be a valuable alternative to P-S, in
      particular in patients with opportunistic bacterial infections.

PMID- 9624474
TI  - beta-Lactamases responsible for resistance to expanded-spectrum cephalosporins in
      Klebsiella pneumoniae, Escherichia coli, and Proteus mirabilis isolates recovered
      in South Africa.
AB  - Although resistance to the expanded-spectrum cephalosporins among members of the
      family Enterobacteriaceae lacking inducible beta-lactamases occurs virtually
      worldwide, little is known about this problem among isolates recovered in South
      Africa. Isolates of Klebsiella pneumoniae, Escherichia coli, and Proteus
      mirabilis resistant to expanded-spectrum cephalosporins recovered from patients
      in various parts of South Africa over a 3-month period were investigated for
      extended-spectrum beta-lactamase production. Antibiotic susceptibility was
      determined by standard disk diffusion and agar dilution procedures. Production of
      extended-spectrum beta-lactamases was evaluated by using the double-disk test,
      and the beta-lactamases were characterized by spectrophotometric hydrolysis
      assays and an isoelectric focusing overlay technique which simultaneously
      determined isoelectric points and general substrate or inhibitor characteristics.
      DNA amplification and sequencing were performed to confirm the identities of
      these enzymes. The P. mirabilis and E. coli isolates were found to produce TEM-26
      type, SHV-2, and SHV-5 extended-spectrum beta-lactamases. An AmpC-related enzyme
      which had a pI of 8.0 and which conferred resistance to cefoxitin as well as the
      expanded-spectrum cephalosporins was found in a strain of K. pneumoniae. This is
      the first study which has identified organisms producing different extended
      spectrum beta-lactamases from South Africa and the first report describing
      strains of P. mirabilis producing a TEM-26-type enzyme. The variety of extended
      spectrum beta-lactamases found among members of the family Enterobacteriaceae
      isolated from major medical centers in South Africa is troubling and adds to the
      growing list of countries where these enzymes pose a serious problem for
      antimicrobial therapy.

PMID- 9624475
TI  - Lysostaphin treatment of experimental methicillin-resistant Staphylococcus aureus
      aortic valve endocarditis.
AB  - The emergence of clinical isolates of methicillin-resistant Staphylococcus aureus
      with reduced susceptibility to vancomycin has prompted a search for new and novel
      therapeutic agents active against S. aureus. Lysostaphin, a peptidase produced by
      Staphylococcus simulans, specifically cleaves the glycine-glycine bonds unique to
      the interpeptide cross-bridge of the S. aureus cell wall. The effectiveness of
      various regimens of dosing with intravenous lysostaphin was compared to that of
      vancomycin in the rabbit model of aortic valve endocarditis caused by a clinical
      methicillin-resistant S. aureus isolate. All animals were treated for a total of
      3 days. The most active regimen, lysostaphin given three times daily, produced
      sterile vegetations in 10 of 11 treated rabbits, with a mean reduction in
      vegetation bacterial counts of 8.5 log10 CFU/g compared to the counts in the
      untreated controls. In contrast, vancomycin given twice daily sterilized no
      vegetations and reduced vegetation bacterial counts by only 4.8 log10 CFU/g.
      Lysostaphin given once daily was less effective, reducing mean vegetation
      bacterial counts by only 3.6 log10 CFU/g, but the combination of lysostaphin once
      daily and vancomycin twice daily reduced the mean vegetation bacterial density by
      7.5 log10 CFU/g, a result that was significantly better than that for either
      regimen alone (P < 0.05). Lysostaphin was well tolerated by the rabbits, with no
      evidence of immunological reactions following up to 9 weeks of intravenous
      administration. We conclude that lysostaphin given alone or in combination with
      vancomycin is more effective in the treatment of experimental methicillin
      resistant S. aureus aortic valve endocarditis than vancomycin alone.

PMID- 9624476
TI  - In vivo efficacies of amoxicillin and cefuroxime against penicillin-resistant
      Streptococcus pneumoniae in a gerbil model of acute otitis media.
AB  - The comparative efficacies of amoxicillin and cefuroxime against acute otitis
      media caused by a penicillin-resistant (MIC, 2 micrograms/ml) Streptococcus
      pneumoniae strain were assessed in a gerbil model by challenging each ear with
      10(7) bacteria through transbullar instillation. Each antibiotic was tested at
      two doses (5 and 20 mg/kg of body weight) administered at 2, 10, and 18 h
      postinoculation. Samples were obtained from the middle ear (ME) on days 3 and 7
      postinoculation for determination of bacterial counts. Only amoxicillin, at both
      doses, was able to significantly halt the weight loss in animals, reducing both
      the number of culture-positive animals and the bacterial concentration in ME
      samples versus the values for untreated animals. Comparison of the efficacies
      between the antibiotics, determined by their ability to achieve culture-negative
      ME specimens, showed that amoxicillin at 5 mg/kg was significantly more active
      than cefuroxime at the same dose. The use of higher doses of either amoxicillin
      or cefuroxime did not produce significantly better results than those obtained
      with the lower dose but caused a greater inflammatory response. The more
      favorable results obtained with amoxicillin compared with those obtained with
      cefuroxime could be related to the antimicrobial susceptibility of the
      pneumococcal strain (MICs and minimum bactericidal concentrations of 1 and 1
      microgram/ml and 4 and 4 micrograms/ml for amoxicillin and cefuroxime,
      respectively) as well as to the better pharmacokinetic parameters obtained with
      amoxicillin.

PMID- 9624477
TI  - Changes in MIC alter responses of Pseudomonas aeruginosa to tobramycin exposure.
AB  - The pharmacokinetic parameters determining antibiotic efficacy are peak
      concentrations (Cmax), minimum (trough) concentrations (Cmin), and area under the
      concentration-time curve (AUC). There is general agreement about the importance
      of Cmax and AUC for aminoglycosides, but this is not so for maintenance of Cmin.
      With in vitro exposures modelling in vivo administration, Pseudomonas aeruginosa
      reference strain ATCC 27853 (MIC, 1 mg/liter) and a higher-MIC (relatively
      resistant) clinical isolate (MIC, 4 mg/liter) were used to explore bacteriostatic
      and bactericidal outcomes. With P. aeruginosa ATCC 27853, kill followed a
      complete bolus profile with a 30-min postdistribution peak (Cpeak30) of 10
      mg/liter. The clinical isolate required a Cpeak30 bolus profile of 20 mg/liter
      for kill, and there was no difference between the efficacies of the bolus and
      infusion exposures. Bolus profiles that were truncated at 8.5 h and producing
      sublethal effects were then combined with a wide range of Cmins. With a Cpeak30
      profile of 8 mg/liter, P. aeruginosa ATCC 27853 showed a graded bacteriostatic
      response until a Cmin of > or = 0.8 mg/liter, when complete kill resulted. In
      contrast, bactericidal effects on the clinical isolate required a Cpeak30 profile
      of 18 mg/liter with a Cmin of > or = 1.0 mg/liter. Therefore, Cmin also
      contributes to the bactericidal effect of tobramycin, with requirements showing
      minor variation with change in MIC. Dosing principles for relatively resistant
      (higher-MIC) organisms are suggested from the data. Relatively higher
      aminoglycoside doses via infusion regimens are likely to be needed to generate
      higher peak concentrations and higher AUC values necessary for bactericidal
      effect in resistant organisms. Maintenance of trough concentrations on the order
      of 1.0 mg/liter during the interdose interval will tend to guard against the
      possibility of inadequate peak and AUC exposures for kill.

PMID- 9624478
TI  - Initial concentration-time profile of gentamicin determines efficacy against
      Enterobacter cloacae ATCC 13047.
AB  - In vitro studies were designed to investigate the influence of peak drug
      concentration (Cmax), the area under the concentration-time curve (AUC), and,
      consequently, the trough concentration on the bactericidal effects of gentamicin
      against Enterobacter cloacae (MIC, 0.5 mg/liter) by simulating bolus versus
      infusion administration and bolus dosing with altered drug clearance. Bacteria in
      the lag phase were exposed to gentamicin concentration-time profiles modelling
      either bolus or infusion dosing (AUC constant, Cmax changing) with 30-min
      postdose peak concentrations (Cpeak30) of 4, 6, 8, and 10 mg/liter or bolus
      dosing with normal and double drug clearance (Cmax constant, AUC changing)
      corresponding to normal clearance profiles with Cpeak30 of 6 and 8 mg/liter.
      Exposure to gentamicin caused early bactericidal effects apparent by 2 h,
      followed by variable bacteriostatic and recovery phases. Exposure to bolus
      profiles resulted in greater bactericidal activity than the corresponding
      infusion profile up to a Cpeak30 of 8 mg/liter. At a Cpeak30 of 10 mg/liter,
      there were no differences in bactericidal effect. Double clearance profiles had a
      reduced bactericidal effect at 6 mg/liter compared to the corresponding normal
      clearance profile, but no differences in bactericidal effect were observed for 8
      mg/liter double and normal clearance profiles. These results suggest that the
      initial exposure (i.e., 0 to 30 min) is a more important determinant for
      bacterial killing than the AUC or trough concentration for this bacterium.
      Subject to confirmation of these findings with other gram-negative bacteria, to
      optimize aminoglycoside efficacy the initial exposure (Cmax) should be maximized
      by giving higher doses or bolus administration at intervals which may not produce
      detectable trough concentrations. Clinical trials with a broad range of patients,
      especially those with higher clearance, would confirm these in vitro observations
      and define optimal dosing recommendations.

PMID- 9624479
TI  - Recombinant expression and characterization of the major beta-lactamase of
      Mycobacterium tuberculosis.
AB  - New antibiotic regimens are needed for the treatment of multidrug-resistant
      tuberculosis. Mycobacterium tuberculosis has a thick peptidoglycan layer, and the
      penicillin-binding proteins involved in its biosynthesis are inhibited by
      clinically relevant concentrations of beta-lactam antibiotics. beta-Lactamase
      production appears to be the major mechanism by which M. tuberculosis expresses
      beta-lactam resistance. beta-Lactamases from the broth supernatant of 3- to 4
      week-old cultures of M. tuberculosis H37Ra were partially purified by sequential
      gel filtration chromatography and chromatofocusing. Three peaks of beta-lactamase
      activity with pI values of 5.1, 4.9, and 4.5, respectively, and which accounted
      for 10, 78, and 12% of the total postchromatofocusing beta-lactamase activity,
      respectively, were identified. The beta-lactamases with pI values of 5.1 and 4.9
      were kinetically indistinguishable and exhibited predominant penicillinase
      activity. In contrast, the beta-lactamase with a pI value of 4.5 showed
      relatively greater cephalosporinase activity. An open reading frame in cosmid Y49
      of the DNA library of M. tuberculosis H37Rv with homology to known class A beta
      lactamases was amplified from chromosomal DNA of M. tuberculosis H37Ra by PCR and
      was overexpressed in Escherichia coli. The recombinant enzyme was kinetically
      similar to the pI 5.1 and 4.9 enzymes purified directly from M. tuberculosis. It
      exhibited predominant penicillinase activity and was especially active against
      azlocillin. It was inhibited by clavulanic acid and m-aminophenylboronic acid but
      not by EDTA. We conclude that the major beta-lactamase of M. tuberculosis is a
      class A beta-lactamase with predominant penicillinase activity. A second, minor
      beta-lactamase with relatively greater cephalosporinase activity is also present.

PMID- 9624480
TI  - Assessment of antifungal activities of fluconazole and amphotericin B
      administered alone and in combination against Candida albicans by using a dynamic
      in vitro mycotic infection model.
AB  - We evaluated the pharmacodynamic activities of fluconazole and amphotericin B
      given alone and in combination against Candida albicans by using an in vitro
      model of bloodstream infection that simulates human serum pharmacokinetic
      parameters for these antifungals. Fluconazole was administered as a bolus into
      the model to simulate regimens of 200 mg every 24 h (q24 h) and 400 mg q24 h.
      Amphotericin B was administered at doses producing the peak concentration (2.4
      micrograms/ml) observed with a regimen of 1 mg/kg of body weight q24 h. A
      combination regimen of fluconazole (400 mg q24 h) and amphotericin B (1 mg/kg q24
      h) administered simultaneously and as a staggered regimen (amphotericin B bolus
      given 8 h after fluconazole bolus) was also simulated in the model to
      characterize possible antagonism between these agents. Fluconazole alone and
      amphotericin B alone demonstrated fungistatic (< 99.9% reduction in numbers of
      CFU per milliliter from the starting inoculum) and fungicidal (> 99.9% reduction)
      activity, respectively. When fluconazole and amphotericin B were administered
      simultaneously, fungicidal activity similar to that observed with amphotericin B
      alone was observed. Staggered administration of fluconazole and amphotericin B,
      however, resulted in a substantial reduction of the fungicidal activity of
      amphotericin B, producing fungistatic activity similar to that observed with
      noncombination fluconazole regimens. These results demonstrate the usefulness of
      this model for comparing the in vitro pharmacodynamic characteristics of
      different antifungal regimens and support the theory of azole-polyene antagonism.
      The effects of this antagonism on the in vivo activity and clinical usefulness of
      combination antifungal therapy, however, remain to be determined.

PMID- 9624481
TI  - Evaluation of endpoints for antifungal susceptibility determinations with
      LY303366.
AB  - We have previously reported poor correlation between the in vitro fungicidal
      activity of LY303366 and MIC results in RPMI medium based upon the manufacturer's
      suggested susceptibility endpoint, lack of visual growth. Additionally, we have
      noted a significant trailing effect with LY303366 when MICs are determined in
      RPMI medium. These observations have led us to evaluate an alternative
      susceptibility endpoint for LY303366, an 80% reduction in growth compared with
      control (similar to that utilized for azoles). Two isolates each of Candida
      albicans, Candida glabrata, and Candida tropicalis were selected for testing.
      MICs were determined for LY303366 in RPMI 1640 medium buffered with
      morpholinepropanesulfonic acid. MICs were determined with suggested (MIC100) and
      experimental (MIC80) endpoints. The minimal fungicidal concentration (MFC) of
      LY303366 for each isolate was also determined. Time-kill curves were determined
      in RPMI medium with each isolate at concentrations of LY303366 ranging from 0.125
      to 16x MIC80 to assess the correlation between MIC80 and fungicidal activity.
      Lastly, fungi exposed to LY303366 were examined via scanning electron microscope
      (SEM) for evidence of drug-induced ultrastructure change. MIC80s for test
      isolates ranged from 0.015 to 0.12 microgram/ml and were consistently three to
      five wells less than MIC100s. Good correlation was observed between fungicidal
      activity, as assessed by kill curves, and the MIC80. SEM data revealed
      significant ultrastructure changes induced by LY303366 even at sub-MIC80s. Based
      on our results demonstrating better correlation between MIC80 and fungicidal
      activity, i.e., time-kill curves and MFCs, we suggest that 80% reduction in
      visible growth be utilized as the endpoint for susceptibility determinations with
      LY303366 in RPMI medium.

PMID- 9624482
TI  - A new ketolide, HMR 3004, active against streptococci inducibly resistant to
      erythromycin.
AB  - HMR 3004 is a new hydrazono ketolide characterized by a 3-keto function instead
      of the cladinose moiety. The effect of this antimicrobial agent on inducible and
      constitutive macrolide-lincosamide-streptogramin B (MLSB) resistance was tested
      in a lacZ reporter system under control of several ermAM-like attenuator
      variants. For one constitutively resistant Streptococcus agalactiae strain, three
      inducibly resistant Streptococcus pneumoniae strains, and one inducibly resistant
      Enterococcus faecalis strain, the attenuators fused with lacZ were cloned into
      the shuttle plasmid pJIM2246 and the plasmid was introduced into Staphylococcus
      aureus RN4220. For the wild-type attenuators, HMR 3004 was a very weak inducer,
      unlike its cladinose counterpart RU 6652 and erythromycin. As expected, for the
      fusion originating from the constitutively resistant S. agalactiae strain, the
      level of uninduced beta-galactosidase synthesis was high. For one S. pneumoniae
      attenuator, mutations in the 3' end of the attenuator that weakened the stem-loop
      structure that sequesters the ribosome-binding site and start codon for ermAM
      methylase could explain the high level of uninduced beta-galactosidase produced.
      For streptococci, the activity of HMR 3004 correlated with the basal level of
      beta-galactosidase synthesized. The weak inducer activity of HMR 3004 explained
      its activity against inducibly MLSB-resistant S. pneumoniae but did not correlate
      with the moderate activity of the antibiotic against inducibly resistant E.
      faecalis.

PMID- 9624483
TI  - Moxifloxacin in the therapy of experimental pneumococcal meningitis.
AB  - The activity of moxifloxacin (BAY 12-8039) against a Streptococcus pneumoniae
      type 3 strain (MIC and minimum bactericidal concentration [MBC] of moxifloxacin,
      0.06 and 0.25 microgram/ml, respectively; MIC and MBC of ceftriaxone, 0.03 and
      0.06 microgram/ml, respectively) was determined in vitro and in a rabbit model of
      meningitis. Despite comparable bactericidal activity, 10 micrograms of
      moxifloxacin per ml released lipoteichoic and teichoic acids less rapidly than 10
      micrograms of ceftriaxone per ml in vitro. Against experimental meningitis, 10 mg
      of moxifloxacin per kg of body weight per ml reduced the bacterial titers in
      cerebrospinal fluid (CSF) almost as rapidly as ceftriaxone did (mean +/- standard
      deviation, -0.32 +/- 0.14 versus -0.39 +/- 0.11 delta log CFU/ml/h). The activity
      of moxifloxacin could be described by a sigmoid dose-response curve with a
      maximum effect of -0.33 delta log CFU/ml/h and with a dosage of 1.4 mg/kg/h
      producing a half-maximal effect. Maximum tumor necrosis factor activity in CSF
      was observed later with moxifloxacin than with ceftriaxone (5 versus 2 h after
      the initiation of treatment). At 10 mg/kg/h, the concentrations of moxifloxacin
      in CSF were 3.8 +/- 1.2 micrograms/ml. Adjunctive treatment with dexamethasone at
      1 mg/kg prior to the initiation of antibiotic treatment only marginally reduced
      the concentrations of moxifloxacin in CSF (3.3 +/- 0.6 micrograms/ml). In
      conclusion, moxifloxacin may qualify for use in the treatment of S. pneumoniae
      meningitis.

PMID- 9624484
TI  - Oral antimicrobial prophylaxis in bone marrow transplant recipients: randomized
      trial of ciprofloxacin versus ciprofloxacin-vancomycin.
AB  - The optimal oral antimicrobial prophylactic regimen for bone marrow transplant
      recipients remains to be elucidated. We randomized 84 patients to receive either
      oral ciprofloxacin or ciprofloxacin plus vancomycin at hospital admission.
      Patients were monitored for bacteremias and clinical parameters, and stool and
      throat swab surveillance cultures were performed. The addition of vancomycin
      resulted in a significant decrease in the frequency of patients with surveillance
      cultures positive for coagulase-negative staphylococci (stool cultures, 44 versus
      23%; throat swab cultures, 37 versus 19%) and alpha-hemolytic streptococci
      (throat swab cultures, 90 versus 60%). The frequencies of positivity for Candida
      spp. and gram-negative organisms on surveillance cultures were comparable.
      Despite these results, no differences in the incidences of bacteremias (12 of 41
      versus 12 of 43 patients) or clinical parameters such as number of days to first
      fever, total number of febrile days, length of stay, and number of transfusions
      could be demonstrated. Because of a lack of efficacy of vancomycin and emerging
      problems with vancomycin-resistant isolates, vancomycin should not be used in
      oral antimicrobial prophylaxis regimens.

PMID- 9624485
TI  - Novel antibiotic susceptibility tests by the ATP-bioluminescence method using
      filamentous cell treatment.
AB  - Antimicrobial susceptibility testing by the ATP-bioluminescence method has been
      noted for its speed; it provides susceptibility results within 2 to 5 h. However,
      several disagreements between the ATP method and standard methodology have been
      reported. The present paper describes a novel ATP method in a 3.5-h test which
      overcomes these deficiencies through the elimination of false-resistance
      discrepancies in tests on gram-negative bacteria with beta-lactam agents. In our
      test model using Pseudomonas aeruginosa and piperacillin, it was shown that ATP
      in filamentous cells accounted for the false resistance. We found that 0.5% 2
      amino-2-methyl-1,3-propanediol (AMPD) extracted ATP from the filamentous cells
      without affecting normal cells and that 0.3 U of adenosine phosphate deaminase
      (APDase)/ml simultaneously digested the extracted ATP. We used the mixture of
      these reagents for the pretreatment of cells in a procedure we named filamentous
      cell treatment, prior to ATP measurements. This novel ATP method with the
      filamentous cell treatment eliminated false-resistance discrepancies in tests on
      P. aeruginosa with beta-lactam agents, including piperacillin, cefoperazone,
      aztreonam, imipenem-cilastatin, ceftazidime, and cefsulodin. Furthermore, this
      novel methodology produced results which agreed with those of the standard
      microdilution method in other tests on gram-negative and gram-positive bacteria,
      including P. aeruginosa, Escherichia coli, Staphylococcus aureus, and
      Enterococcus faecalis, for non-beta-lactam agents, such as fosfomycin, ofloxacin,
      minocycline, and aminoglycosides. MICs obtained by the novel ATP method were also
      in agreement with those obtained by the agar dilution method of susceptibility
      testing. From these results, it was shown that the novel ATP method could be used
      successfully to test the activities of antimicrobial agents with the elimination
      of the previously reported discrepancies.

PMID- 9624486
TI  - Comparison of in vitro antifungal activities of free and liposome-encapsulated
      nystatin with those of four amphotericin B formulations.
AB  - The in vitro activity of a multilamellar liposomal formulation of nystatin
      (Nyotran) was compared with those of free nystatin and four pharmaceutical
      preparations of amphotericin B. MICs for 200 isolates of two Aspergillus spp.,
      seven Candida spp., and Cryptococcus neoformans were determined by a broth
      microdilution adaptation of the method recommended by the National Committee for
      Clinical Laboratory Standards. Minimum lethal concentrations (MLCs) of the six
      antifungal preparations were also determined. Both nystatin formulations
      possessed fungistatic and fungicidal activities against the 10 species tested.
      Liposomal nystatin appeared to be as active as free nystatin, with MICs and MLCs
      that were similar to, or lower than, those of the latter. Neither formulation of
      nystatin was as active as amphotericin B deoxycholate (Fungizone) or amphotericin
      B lipid complex (Abelcet), but both were more effective than liposomal
      amphotericin B (AmBisome). Our results suggest that further evaluation of
      liposomal nystatin is justified.

PMID- 9624487
TI  - Pharmacokinetics of sparfloxacin in the serum and vitreous humor of rabbits:
      physicochemical properties that regulate penetration of quinolone antimicrobials.
AB  - We have used a recently described animal model to characterize the ocular
      pharmacokinetics of sparfloxacin in vitreous humor of uninfected albino rabbits
      following systemic administration and direct intraocular injection. The
      relationships of lipophilicity, protein binding, and molecular weight to the
      penetration and elimination of sparfloxacin were compared to those of
      ciprofloxacin, fleroxacin, and ofloxacin. To determine whether elimination was
      active, elimination rates following direct injection with and without probenecid
      or heat-killed bacteria were compared. Sparfloxacin concentrations were measured
      in the serum and vitreous humor by a biological assay. Protein binding and
      lipophilicity were determined, respectively, by ultrafiltration and oil-water
      partitioning. Pharmacokinetic parameters were characterized with RSTRIP, an
      iterative, nonlinear, weighted, least-squares-regression program. The
      relationship between each independent variable and mean quinolone concentration
      or elimination rate in the vitreous humor was determined by multiple linear
      regression. The mean concentration of sparfloxacin in the vitreous humor was
      59.4% +/- 12.2% of that in serum. Penetration of sparfloxacin, ciprofloxacin,
      fleroxacin, and ofloxacin into, and elimination from, the vitreous humor
      correlated with lipophilicity (r2 > 0.999). The linear-regression equation
      describing this relationship was not improved by including the inverse of the
      square root of the molecular weight and/or the degree of protein binding.
      Elimination rates for each quinolone were decreased by the intraocular
      administration of probenecid. Heat-killed Staphylococcus epidermidis decreased
      the rate of elimination of fleroxacin. Penetration of sparfloxacin into the
      noninflamed vitreous humor was greater than that of any quinolone previously
      examined. There was an excellent correlation between lipophilicity and vitreous
      entry or elimination for sparfloxacin as well as ciprofloxacin, fleroxacin, and
      ofloxacin. There are two modes of quinolone translocation into and out of the
      vitreous humor: diffusion into the eye and both diffusion and carrier-mediated
      elimination out of the vitreous humor.

PMID- 9624488
TI  - Antifungal activity of 3'-deoxyadenosine (cordycepin).
AB  - The antifungal activity of the nucleoside analog 3'-deoxyadenosine (cordycepin)
      was studied in a murine model of invasive candidiasis. When protected from
      deamination by either deoxycoformycin or coformycin, both of which are adenosine
      deaminase inhibitors, cordycepin exhibited potent antifungal efficacy, as
      demonstrated by prolongation of survival and a decrease in CFU in the kidneys of
      mice treated with cordycepin plus an adenosine deaminase inhibitor. The
      antifungal effect was seen with three different Candida isolates: Candida
      albicans 64, a relatively fluconazole-resistant clinical isolate of C. albicans
      (MIC, 16 micrograms/ml), and the fluconazole-resistant Candida krusei. Cordycepin
      and related compounds may provide another avenue for the discovery of clinically
      useful antifungal drugs.

PMID- 9624489
TI  - Use of a continuous-culture biofilm system to study the antimicrobial
      susceptibilities of Gardnerella vaginalis and Lactobacillus acidophilus.
AB  - Gardnerella vaginalis and Lactobacillus acidophilus have been shown to grow to
      high titers in a simple biofilm system. This system was used in the present
      investigation to compare the biofilm-eradicating concentrations (BECs) of
      amoxicillin, clindamycin, erythromycin, and metronidazole to standard tube MIC
      and minimum bactericidal concentration (MBC) results. With the lactobacillus, the
      BEC/tube MBC ratio was at least 16:1, while for G. vaginalis the ratio varied
      from 2:1 to 512:1. The simple continuous-culture system used in the present
      investigation is ideal for investigating the BEC for bacteria involved in complex
      ecological situations such as bacterial vaginosis and may be useful for the
      identification of the most effective and selective antibiotic therapy.

PMID- 9624490
TI  - Pharmacokinetics and safety of a new parenteral carbapenem antibiotic, biapenem
      (L-627), in elderly subjects.
AB  - The pharmacokinetics and tolerability of a new parenteral carbapenem antibiotic,
      biapenem (L-627), were studied in healthy elderly volunteers aged 65 to 74 years
      (71.6 +/- 2.7 years [mean +/- standard deviation], n = 5; group B) and > or = 75
      years (77.8 +/- 1.9 years, n = 5; group C), following single intravenous doses
      (300 and 600 mg), and compared with those of healthy young male volunteers aged
      20 to 29 years (23.0 +/- 3.5 years, n = 5; group A). The agent was well tolerated
      in all three age groups. Serial blood and urine samples were analyzed for
      biapenem to obtain key pharmacokinetic parameters by both two-compartment model
      dependent and -independent methods. The maximum plasma concentration and area
      under plasma concentration-versus-time curve (AUC) increased in proportion to the
      dose in all three groups. Statistically significant age-related effects for AUC,
      total body clearance, and renal clearance (CLR) were found, while elimination
      half-life (t1/2 beta) and percent cumulative recovery from urine of unchanged
      drug (% UR) remained unaltered (t1/2 beta, 1.51 +/- 0.42 [300 mg] and 2.19 +/-
      0.64 [600 mg] h [group A], 1.82 +/- 1.14 and 1.45 +/- 0.36 h [group B], and 1.75
      +/- 0.23 and 1.59 +/- 0.18 h [group C]; % UR, 52.6% +/- 3.0% [300 mg] and 53.1%
      +/- 5.1% [600 mg] [group A], 46.7% +/- 7.4% and 53.0% +/- 4.8% [group B], and
      50.1% +/- 5.2% and 47.1% +/- 7.6% [group C]). A significant linear correlation
      was observed between the CLR of biapenem and creatinine clearance at the dose of
      300 mg but not at 600 mg. The steady-state volume of distribution tended to be
      decreased with age, although not significantly. Therefore, the age-related
      changes in parameters of biapenem described above were attributable to the
      combination of decreased lean body mass and lowered renal function of the elderly
      subjects. However, the magnitude of those changes does not necessitate dosage
      adjustment in elderly patients with normal renal function for their age.

PMID- 9624492
TI  - Screening for novel antimicrobials from encoded combinatorial libraries by using
      a two-dimensional agar format.
AB  - A sensitive lawn-based format has been developed to screen bead-tethered
      combinatorial chemical libraries for antimicrobial activity. This method has been
      validated with beads linked to penicillin V via a photocleavable chemical linker
      in several analyses including a spike-and-recover experiment. The lawn-based
      screen sensitivity was modified to detect antibacterial compounds of modest
      potency, and a demonstration experiment with a naive combinatorial library of
      over 46,000 individual triazines was evaluated for antibacterial activity.
      Numerous hits were identified, and both active and inactive compounds were
      resynthesized and confirmed in traditional broth assays. This demonstration
      experiment suggests that novel antimicrobial compounds can be easily identified
      from very large combinatorial libraries of small, nonpeptidic compounds.

PMID- 9624493
TI  - Quantitative structure-activity relationship studies of a series of sulfa drugs
      as inhibitors of Pneumocystis carinii dihydropteroate synthetase.
AB  - Sulfone and sulfanilamide sulfa drugs have been shown to inhibit dihydropteroate
      synthetase (DHPS) isolated from Pneumocystis carinii. In order to develop a
      pharmacophoric model for this inhibition, quantitative structure-activity
      relationships (QSAR) for sulfa drugs active against DHPS have been studied.
      Accurate 50% inhibitory concentrations were collected for 44 analogs, and other
      parameters, such as partition coefficients and molar refractivity, were
      calculated. Conventional multiple regression analysis of these data did not
      provide acceptable QSAR. However, three-dimensional QSAR provided by comparative
      molecular field analysis did give excellent results. Upon removal of poorly
      correlated analogs, a data set of 36 analogs, all having a common NHSO2 group,
      provided a cross-validated r2 value of 0.699 and conventional r2 value of 0.964.
      The resulting pharmacophore model should be useful for understanding and
      predicting the binding of DHPS by new sulfa drugs.

PMID- 9624491
TI  - Characterization of a murine monoclonal antibody to Cryptococcus neoformans
      polysaccharide that is a candidate for human therapeutic studies.
AB  - The murine monoclonal antibody (MAb) 18B7 [immunoglobulin G1(kappa)] is in
      preclinical development for treatment of Cryptococcus neoformans infections. In
      anticipation of its use in humans, we defined the serological and biological
      properties of MAb 18B7 in detail. Structural comparison to the related protective
      MAb 2H1 revealed conservation of the antigen binding site despite several amino
      acid differences. MAb 18B7 was shown by immunofluorescence and agglutination
      studies to bind to all four serotypes of C. neoformans, opsonize C. neoformans
      serotypes A and D, enhance human and mouse effector cell antifungal activity, and
      activate the complement pathway leading to deposition of complement component 3
      (C3) on the cryptococcal capsule. Administration of MAb 18B7 to mice led to rapid
      clearance of serum cryptococcal antigen and deposition in the liver and spleen.
      Immunohistochemical studies revealed that MAb 18B7 bound to capsular
      glucuronoxylomannan in infected mouse tissues. No reactivity of MAb 18B7 with
      normal human, rat, or mouse tissues was detected. The results show that both the
      variable and constant regions of MAb 18B7 are biologically functional and support
      the use of this MAb in human therapeutic trials.

PMID- 9624494
TI  - Ceftazidime and aztreonam resistance in Providencia stuartii: characterization of
      a natural TEM-derived extended-spectrum beta-lactamase, TEM-60.
AB  - A plasmid-encoded beta-lactamase produced from a clinical strain of Providencia
      stuartii has been purified and characterized. The gene coding for the beta
      lactamase was cloned and sequenced. It appears to be a new natural TEM-derived
      enzyme, named TEM-60. Point mutations (Q39K, L51P, E104K, and R164S) are present
      with respect to the TEM-1 enzyme; the mutation L51P has never been previously
      reported, with the exception of the chromosomally encoded extended-spectrum beta
      lactamase PER-1. Kinetic parameters relative to penicillins, cephalosporins, and
      monobactams other than mechanism-based inactivators were related to the in vitro
      susceptibility phenotype.

PMID- 9624495
TI  - Analysis of the pharmacokinetic interaction between cephalexin and quinapril by a
      nonlinear mixed-effect model.
AB  - Oligopeptidic drugs such as beta-lactams and angiotensin-converting enzyme
      inhibitors share the same carriers in humans and animals, which results in
      possible pharmacokinetic interactions. To model such interactions, the effects of
      quinapril on cephalexin pharmacokinetics were investigated in rats. Blood
      cephalexin concentrations were measured by liquid chromatography, and the data
      were analyzed by a noncompartmental method and by fitting a bicompartmental model
      by a nonlinear mixed-effect modeling approach. Five groups of eight rats were
      examined. In the first three groups, cephalexin elimination kinetics after intra
      arterial administration alone or in combination with quinapril given by the
      parenteral or the oral route were studied, and the occurrence of a
      pharmacokinetic interaction was not revealed. The absence of an effect of
      quinapril on cephalexin elimination after parenteral administration might be
      explained either by the higher affinity of cephalexin for the renal anionic
      transport system than that of quinapril or by the much higher concentrations of
      cephalexin than those of quinapril. In the last two groups, cephalexin was
      administered by the oral route alone or in combination with quinapril. The mean
      area under the concentration-time curve (AUC) for cephalexin was increased by ca.
      30% by coadministration of quinapril (40.1 versus 31.4 mg.h/liter; P = 0.04). The
      mean elimination clearance of cephalexin was significantly decreased by
      quinapril, from 0.81 to 0.64 liter/h/kg of body weight (P < 0.05), probably by
      competitive inhibition of cephalexin secretion at the tubular level. The mean
      absorption rate constant of cephalexin was significantly lowered by quinapril
      (from 0.249 to 0.177 h-1; P < 0.01), without modification of the extent of
      absorption (89%). This pharmacokinetic interaction could be explained by
      competitive inhibition of cephalexin active transport by quinapril at the
      intestinal level.

PMID- 9624496
TI  - Chondrotoxicity and toxicokinetics of sparfloxacin in juvenile rats.
AB  - Sparfloxacin is a fluoroquinolone with improved antibacterial activity against
      gram-positive pathogens. Like other quinolones, use of this drug is
      contraindicated in children and adolescents because of its potential
      chondrotoxicity in juveniles. We performed histological and immunohistochemical
      studies on the knee joint cartilage in 5-week-old rats after treatment with 600
      or 1,800 mg of sparfloxacin/kg of body weight. Treatment with single or multiple
      oral doses of 600 mg of sparfloxacin/kg was not sufficient to induce joint
      cartilage lesions. However, five of eight rats treated with a single oral dose of
      1,800 mg of sparfloxacin/kg of body weight showed typical cartilage lesions in
      the femoral part of the knee joint. The concentrations of the drug in plasma
      measured 0.25, 0.75, 1.5, 3, 6, 12, and 24 h after the administration of an oral
      dose of 600 mg of sparfloxacin/kg were 6.3 +/- 1.8, 9.2 +/- 1.7, 9.6 +/- 2.7,
      13.0 +/- 1.8, 12.3 +/- 1.6, 3.4 +/- 0.4, and 0.30 +/- 0.20 mg/liter, respectively
      (mean +/- standard deviation [SD]; n = 5 to 6 per group). The concentrations in
      plasma measured 0.75, 1.5, 3, 6, 24, and 48 h after the administration of an oral
      dose of 1,800 mg of sparfloxacin/kg were 10.9 +/- 1.5, 15.9 +/- 1.6, 19.1 +/-
      1.7, 14.9 +/- 3.1, 4.1 +/- 0.6, and 0.46 +/- 0.37 mg/liter, respectively (mean +/
      SD; n = 3 to 4 per group). The concentrations of sparfloxacin in joint cartilage
      were significantly higher at all time points studied (114.8 +/- 80, 99.4 +/-
      31.5, 84.9 +/- 16.8, 44.4 +/- 13.9, and 14.2 +/- 4.8 mg of sparfloxacin/kg at
      1.5, 3, 6, 24, and 48 h after the administration of 1,800 mg/kg, respectively).
      The range of concentrations in bone were similar to the range of concentrations
      in cartilage (peak, 115 +/- 12 mg/kg after 3 h). Our data indicate that
      chondrotoxic doses of sparfloxacin in juvenile rats are approximately 300 times
      higher than the doses of sparfloxacin used therapeutically (1,800 versus
      approximately 6 mg/kg of body weight), but due to species differences in
      kinetics, concentrations in plasma differ by a factor of only approximately 15.
      More data on quinolone concentrations in cartilage from animals and humans could
      provide a better basis for a reasonable risk assessment.

PMID- 9624497
TI  - Delivery of the non-membrane-permeative antibiotic gentamicin into mammalian
      cells by using Shigella flexneri membrane vesicles.
AB  - We developed a model to test whether non-membrane-permeative therapeutic agents
      such as gentamicin could be delivered into mammalian cells by means of bacterial
      membrane vesicles. Many gram-negative bacteria bleb off membrane vesicles (MVs)
      during normal growth, and the quantity of these vesicles can be increased by
      brief exposure to gentamicin (J. L. Kadurugamuwa and T. J. Beveridge, J.
      Bacteriol. 177:3998-4008, 1995), which can be entrapped within the MVs.
      Gentamicin-induced MVs (g-MVs) were isolated from Shigella flexneri and contained
      85 +/- 2 ng of gentamicin per microgram of MV protein. Immunogold electron
      microscopic labeling of thin sections with antibodies specific to S. flexneri
      lipopolysaccharide (LPS) demonstrated the adherence and subsequent engulfment of
      MVs by the human Henle 407 intestinal epithelial cell line. Further incubation of
      g-MVs with S. flexneri-infected Henle cells revealed that the g-MVs penetrated
      throughout the infected cells and reduced the intracellular pathogen by
      approximately 1.5 log10 CFU in the first hour of incubation. Antibiotic was
      detected in the cytoplasms of host cells, indicating the intracellular placement
      of the drug following the penetration of g-MVs. Soluble antibiotic, added as a
      fluid to the tissue culture growth medium, had no effect on intracellular
      bacterial growth, confirming the impermeability of the cell membranes of the
      tissue to gentamicin. Western blot analysis of MVs with S. flexneri Ipa-specific
      antibodies demonstrated that the invasion protein antigens IpaB, IpaC, and IpaD
      were present in MVs. Being bilayered, with outer faces composed of LPS and Ipa
      proteins, these MVs were readily engulfed by the otherwise impermeable membranes
      and eventually liberated their contents into the cytoplasmic substance of the
      host tissue.

PMID- 9624498
TI  - Antiviral activities of 9-R-2-phosphonomethoxypropyl adenine (PMPA) and
      bis(isopropyloxymethylcarbonyl)PMPA against various drug-resistant human
      immunodeficiency virus strains.
AB  - 9-R-2-Phosphonomethoxypropyl adenine (PMPA) is an acyclic nucleoside phosphonate
      analog that has demonstrated efficacy against human immunodeficiency virus (HIV).
      We recently described the synthesis, metabolism, and biological activities of
      bis(isopropyloxymethylcarbonyl)PMPA [bis(poc)PMPA] as an orally bioavailable
      prodrug for PMPA. Among a large panel of drug-resistant HIV type 1 variants, only
      the K65R virus was resistant to PMPA. K65R virus also showed reduced
      susceptibility to bis(poc)PMPA, although the prodrug could still inhibit these
      viruses at submicromolar, nontoxic concentrations. Among a panel of seven primary
      clinical isolates from patients with diverse treatment histories, only one
      isolate showed reduced susceptibility to PMPA and was found to carry three
      mutations (M41L, T69N, R73K) in its reverse transcriptase catalytic domain.

PMID- 9624499
TI  - Efficacies of zinc-finger-active drugs against Giardia lamblia.
AB  - Twenty-nine of 34 (85%) Zn-finger-active compounds at 300 microM or less
      inhibited the growth of Giardia lamblia. The most active compound, disulfiram
      (Antabuse), was cidal at 1.23 +/- 0.32 microM. In the adult mouse model,
      significant in vivo activity was demonstrated by increased cure rates and
      decreased parasite burdens.

PMID- 9624500
TI  - Different erythromycin resistance mechanisms in group C and group G streptococci.
AB  - Different mechanisms of erythromycin resistance predominate in group C and G
      streptococcus (GCS and GGS, respectively) isolates collected from 1992 to 1995 in
      Finland. Of the 21 erythromycin-resistant GCS and 32 erythromycin-resistant GGS
      isolates, 95% had the mefA or mefE drug efflux gene and 94% had the ermTR
      methylase gene, respectively.

PMID- 9624501
TI  - Mode of action of sulfanilyl fluoroquinolones.
AB  - The mode of action of sulfanilyl fluoroquinolones (NSFQs) was investigated with
      NSFQ-104, NSFQ-105, and some structurally related compounds. Evidence arising
      from interactions with p-aminobenzoic acid and trimethoprim suggested that a
      sulfonamidelike mechanism of action makes little or no contribution to the in
      vitro activity of NSFQs. NSFQ-105 showed an activity that inhibits gyrase
      catalyzed DNA supercoiling that is similar to the activity of other
      fluoroquinolones. Also, NSFQ-105 uptake was decreased by the presence of Mg2+ and
      increased by a lower pH. These results indicate that NSFQs having only one
      ionizable group could exhibit more favorable kinetics of access to the bacterial
      cell than zwitterionic fluoroquinolones.

PMID- 9624502
TI  - Roxithromycin inhibits cytokine production by and neutrophil attachment to human
      bronchial epithelial cells in vitro.
AB  - We evaluated the effect of roxithromycin on cytokine production and neutrophil
      attachment to human airway epithelial cells. Roxithromycin suppressed production
      of interleukin 8 (IL-8), IL-6, and granulocyte-macrophage colony-stimulating
      factor. It inhibited neutrophil adhesion to epithelial cells. Roxithromycin
      modulates local recruitment and activation of inflammatory cells, which may have
      relevance to its efficacy in airway diseases.

PMID- 9624503
TI  - Postantibiotic effect of trovafloxacin against gram-positive and -negative
      organisms.
AB  - Trovafloxacin pneumococcal and staphylococcal postantibiotic effects (PAEs) were
      0.7 to 1.8 and 0.7 to 2.4 h, respectively. For Escherichia coli and Pseudomonas
      aeruginosa, PAEs were 2.4 to 4.4 h. Pneumococcal and staphylococcal
      postantibiotic sub-MIC effects (PA-SMEs) (0.4 times the MIC) were 2.3 to 3.7 and
      2.4 to > 9.2 h, respectively, and E. coli PA-SMEs (0.3 times the MIC) were 6.8 to
      > 12.0 h. For one P. aeruginosa strain, the PA-SME (0.4 times the MIC) was > 10
      h; in the other, rapid bactericidal activity precluded measurement.

PMID- 9624504
TI  - Characterization of the 6'-N-aminoglycoside acetyltransferase gene aac(6')-Iq
      from the integron of a natural multiresistance plasmid.
AB  - The nucleotide sequence of a newly identified amikacin resistance gene, aac(6')
      Iq (551 bp), is reported. It has 68.4 and 94.4% homology with the aac(6')-Ia gene
      and the recently described aac(6')-Ip gene, respectively. Analysis of its
      flanking sequences indicated that it is in the first cassette of a class I
      integron and has an attC site (59-base element) 108 bp in length.

PMID- 9624506
TI  - Pharmacokinetic studies of fluconazole in rabbits characterizing doses which
      achieve peak levels in serum and area under the concentration-time curve values
      which mimic those of high-dose fluconazole in humans.
AB  - We conducted steady-state pharmacokinetic studies with high-dose fluconazole with
      rabbits and human volunteers. We then derived mathematical equations that predict
      the doses of fluconazole that should be given to rabbits to produce 24-h area
      under the concentration-time curve values and maximum concentrations in serum
      that are similar to those measured for humans given 800 to 2,000 mg of
      fluconazole per day. These equations provide a rational basis for designing
      future efficacy studies with rabbits and in evaluating the strength with which
      results of previously conducted studies using rabbit infection models can be
      extrapolated to the clinic.

PMID- 9624505
TI  - In vitro activities of the new ketolide antibiotics HMR 3004 and HMR 3647 against
      Streptococcus pneumoniae in Germany.
AB  - The comparative in vitro activity of HMR 3004 and HMR 3647, new ketolide
      antibiotics, was tested by a standard agar dilution technique against 221
      pneumococcal strains, including isolates with intermediate levels of resistance
      to penicillin and erythromycin-resistant isolates. The ketolides were more active
      than other macrolides and showed excellent activity against erythromycin
      resistant strains. All the strains were inhibited by < or = 2 micrograms of HMR
      3004/ml or by < or = 0.5 microgram of HMR 3647/ml.

PMID- 9624507
TI  - In vitro activity of a new ketolide antibiotic, HMR 3647, against Chlamydia
      pneumoniae.
AB  - The in vitro activities of HMR 3647, roxithromycin, erythromycin, and
      azithromycin against 19 strains of Chlamydia pneumoniae were tested. The MIC at
      which 90% of the isolates are inhibited and the minimum bactericidal
      concentration at which 90% of the isolates are killed of HMR 3647 were 0.25
      microgram/ml (range, 0.015 to 2 micrograms/ml). Nine recently obtained clinical
      isolates from children with pneumonia were more susceptible (MICs, 0.015 to
      0.0625 microgram/ml) than older strains that had been passaged more extensively.

PMID- 9624508
TI  - Antimicrobial susceptibilities of group B streptococci isolated between 1992 and
      1996 from patients with bacteremia or meningitis.
AB  - In vitro testing of 229 group B streptococcal isolates from a variety of patients
      with invasive infections indicated uniform penicillin G susceptibility. However,
      17 (7.4%) isolates were resistant to erythromycin and 8 (3.4%) were resistant to
      clindamycin. These results support the continued use of penicillin G as the drug
      of choice for the treatment and prevention of group B streptococcal disease.

PMID- 9624509
TI  - Susceptibilities of Legionella spp. to newer antimicrobials in vitro.
AB  - The in vitro activities of 13 antimicrobial agents against 30 strains of
      Legionella spp. were determined. Rifapentine, rifampin, and clarithromycin were
      the most potent agents (MICs at which 90% of isolates are inhibited [MIC90s], <
      or = 0.008 microgram/ml). The ketolide HMR 3647 and the fluoroquinolones
      levofloxacin and BAY 12-8039 (MIC90s, 0.03 to 0.06 microgram/ml) were more active
      than erythromycin A or roxithromycin. The MIC90s of dalfopristin-quinupristin and
      linezolid were 0.5 and 8 micrograms/ml, respectively. Based on class
      characteristics and in vitro activities, several of these agents may have
      potential roles in the treatment of Legionella infections.

PMID- 9624511
TI  - Should any hospital-based training for family physicians persist?

PMID- 9624512
TI  - Relationship between spirituality and health is important.

PMID- 9624510
TI  - Contribution of beta-lactamases to beta-lactam susceptibilities of susceptible
      and multidrug-resistant Mycobacterium tuberculosis clinical isolates.
AB  - The beta-lactamases in 154 clinical Mycobacterium tuberculosis strains were
      studied. Susceptibilities to beta-lactam antibiotics, their combination with
      clavulanate (2:1), and two fluoroquinolones were determined in 24 M. tuberculosis
      strains susceptible to antimycobacterial drugs and in nine multiresistant
      strains. All 154 M. tuberculosis isolates showed a single chromosomal beta
      lactamase pattern (pI 4.9 and 5.1). M. tuberculosis beta-lactamase hydrolyzes
      cefotaxime with a maximum rate of 22.5 +/- 2.19 IU/liter (strain 1382). Neither
      amoxicillin, carbenicillin, cefotaxime, ceftriaxone, nor aztreonam was active
      alone. Except for aztreonam, beta-lactam combinations with clavulanate produced
      better antimycobacterial activity.

PMID- 9624513
TI  - Educational guidelines for women's health are available from AAFP.

PMID- 9624514
TI  - Building our sense of place.

PMID- 9624515
TI  - Professional moves: risks, rules, and rewards.

PMID- 9624516
TI  - Effective use of feedback.

PMID- 9624517
TI  - Independent activities for student learning during community-based rotations.

PMID- 9624518
TI  - Unique learning contributions of a family medicine preceptorship.
AB  - BACKGROUND: There is a belief among family medicine educators that a third-year
      family medicine rotation provides unique clinical learning experiences, but there
      is limited research to support this belief. This study identified clinical skills
      performed by third-year medical students only during a community-based family
      medicine preceptorship, even when the family medicine rotation occurs after all
      other required clerkships. METHODS: During 6 academic years (1990-1996), 87 third
      year students completed the family medicine preceptorship as their final rotation
      and rated their experience with 80 clinical activities (preventive health care,
      clinical problem management, and procedures) after completing all required
      clerkships other than family medicine and again after the family medicine
      preceptorship. Ratings measured whether the activities occurred on the family
      medicine rotation, only on other rotations, or combinations of both. RESULTS:
      More than 50% of students who performed five preventive skills (health
      maintenance for adolescents, young adults, middle-aged adults, or senior citizens
      and weight control counseling) gained that experience only during the family
      medicine preceptorship. The majority of students actively managed six clinical
      problems (acute strains and sprains, low back pain, sinusitis, strep throat,
      acute bronchitis, and osteoarthritis) uniquely during the family medicine
      preceptorship. The preceptorship offered few unique opportunities to perform
      procedures. CONCLUSIONS: This family medicine educational experience was not
      merely a repeat of what is experienced on the traditional major rotations. The
      family medicine preceptorship provided a setting where students were able to
      perform several important ambulatory, primary care skills they had not performed
      during their core curriculum of traditional third-year rotations.

PMID- 9624519
TI  - The problem-based medical audit program: influence on family practice residents'
      knowledge and skills.
AB  - BACKGROUND AND OBJECTIVES: Family physicians need to possess the skills to
      conduct audits in their own clinical settings to ensure that their patients
      receive exemplary clinical care. Residency offers an important opportunity for
      physicians to develop these auditing skills. This study describes the
      introduction of a problem-based medical audit program at three teaching units in
      the Department of Family Medicine at McMaster University and the program's effect
      on learner knowledge, skills, and attitudes toward the practice audit. METHODS: A
      survey designed to assess residents' self-rated knowledge, skills, and attitudes
      toward practice audits was distributed before and after residents participated in
      the audit program. RESULTS: Forty-three residents were surveyed; 33 (76.7%)
      completed the initial questionnaire and follow-up questionnaire. Residents
      reported significant improvements in their understanding of the relevance of
      audits, ability to develop a practice audit question, skills in designing
      methodology, and skills needed to conduct an audit independently. Residents also
      reported a moderate increase in their knowledge of statistics needed to complete
      an audit. CONCLUSIONS: The practice audit program at McMaster University uses a
      problem-based model to introduce learners to the concept of the clinical audit.
      The practice audit program successfully improved the residents' self-reported
      ability to conduct an audit and heightened their understanding of the importance
      and relevance of the audit process.

PMID- 9624520
TI  - Teaching outpatient procedures: most common settings, evaluation methods, and
      training barriers in family practice residencies.
AB  - BACKGROUND AND OBJECTIVES: The processes of teaching outpatient procedures in the
      training of primary care physicians have not been widely studied or standardized.
      This study identified the most widely used teaching settings, methods of
      evaluation, and barriers to teaching several key procedures in US family practice
      residencies. METHODS: A survey was sent to directors of family practice residency
      programs. Key issues identified in phone survey data of published experts in
      procedural training were used in developing the survey. RESULTS: Of the 464
      residency directors contacted, 342 (73.7%) returned completed surveys. Results
      showed that the family practice center (FPC) was the most common setting for this
      teaching. Faculty observation was used as a principal evaluation method in most
      programs for all procedures. Several barriers to training were identified as
      "very" or "moderately" important. CONCLUSIONS: While the FPC is the most
      frequently used setting for training in procedures, significant limitations
      include problems of low volume, limited methods of evaluation, scheduling
      difficulties, and lack of faculty interest and skill. Several internal and
      external strategies may be used to alleviate these problems.

PMID- 9624521
TI  - Teaching community-oriented primary care through longitudinal group projects.
AB  - BACKGROUND: Though community-oriented primary care (COPC) has been advocated as
      an effective way of addressing health problems of communities, it is neither
      widely understood nor frequently practiced. Because COPC requires an extended
      period of time, as well as an approach and skills not generally learned in
      medical training, effectively incorporating COPC training into medical education
      is difficult and not frequently attempted. This paper describes a COPC curriculum
      for family practice residents based on required participation in a longitudinal
      group project. METHODS: Residents participated in successive groups that
      completed a COPC project over a 2-year period. Twenty-two of 26 PGY-2 residents
      completed an attitude and knowledge test before and after participation in the
      curriculum. A qualitative evaluation of the curriculum was also performed.
      RESULTS: Pretest and posttest responses showed significant improvement in
      residents' knowledge about COPC and a small but significant decline in attitudes
      toward COPC. Residents' reactions to the curriculum in the qualitative evaluation
      were both positive and negative. Residents enjoyed the group process and found it
      intellectually stimulating. Many reported, however, that they did not feel
      ownership of the project, that working through the four-step systematic COPC
      process was slow and cumbersome, and that they had learned only part of the COPC
      process. Residents consistently reported becoming more aware of the importance of
      discussing the focus of the project (i.e., childhood discipline or domestic
      violence) with their patients and feeling more comfortable initiating such
      discussions. CONCLUSIONS: A COPC curriculum based on required participation in a
      2-year group project promoted completion of substantial projects. There were
      trade-offs in resident experience, including loss of continuity for individual
      residents. Effectively teaching COPC and engaging residents in community-oriented
      activities remains a challenge.

PMID- 9624522
TI  - Residents find clinical practice guidelines valuable as educational and clinical
      tools.
AB  - BACKGROUND AND OBJECTIVES: Information regarding clinical practice guideline
      (CPG) use in residency education is limited. We surveyed a regional population of
      family practice residents to determine use, attitudes, and curricular needs for
      practice guidelines. METHODS: A written survey was developed that measured
      residents' exposure to, frequency of use, attitudes, access, and knowledge about
      use of CPGs. The survey was mailed to 114 family practice residents. RESULTS: The
      response rate was 75%. The most frequently seen guidelines were immunization
      schedules, cancer screening, hyperlipidemia, and hypertension management. The
      residents reported positive attitudes toward CPGs; 75% thought CPGs were easy to
      use, 80% thought they improved their efficiency, 78% thought they improved their
      residency education, and 75% thought they improved patient care. Barriers to
      effective use of practice guidelines were also identified; 20% knew where to find
      guidelines in their clinic, 35% had faculty modeling, and 22% knew how to
      evaluate the validity of a guideline. Eighty-nine percent of respondents desired
      instruction on CPG use and interpretation. CONCLUSIONS: The surveyed family
      practice residents have similar usage rates for CPGs as the literature reports
      for practicing physicians, but residents report more positive attitudes. Barriers
      that prevent effective use of CPGs in training environments include lack of
      critical appraisal abilities and faculty role modeling.

PMID- 9624523
TI  - Care of persons with AIDS in the nursing home.
AB  - BACKGROUND: AIDS is becoming a chronic illness for some patients whose
      significant accumulated functional impairments may limit community-based care.
      Nursing homes can provide an appropriate level of care, although reported
      experience caring for persons with AIDS in this setting is limited. METHODS: A
      retrospective case-series review was conducted in a 242-bed community teaching
      nursing home to describe the initial 26-month experience in providing care for
      patients with AIDS requiring nursing home admission. RESULTS: A total of 42
      admissions by 32 patients with AIDS (mean age = 33.5 years, 81% male) involved a
      shorter length of stay (mean 63.1 days) and higher numbers of medications (mean =
      11.2), facility charges (mean $11,971/admission, $189/day), and greater clinical
      management complexity than usual nursing home patients. Thirteen patients were
      discharged, seven for rehospitalization and six into community settings, although
      ultimately 29 of the 32 patients died in the facility. CONCLUSIONS: AIDS care in
      the nursing home presents significant, distinct challenges in complex management
      and terminal care prioritization.

PMID- 9624524
TI  - Improving diabetes preventive care in a family practice residency program: a case
      study in continuous quality improvement.
AB  - BACKGROUND AND OBJECTIVES: The paradigm of continuous quality improvement (CQI)
      holds promise for application in clinical settings. This paper highlights results
      of a CQI project developed and implemented in a residency-based, ambulatory
      family medicine center for management of non-insulin-dependent diabetes mellitus.
      METHODS: We developed a CQI program that used several indicators of diabetes
      management as measures of quality care. These included dietary counseling,
      exercise counseling, foot care counseling, ophthalmology referral, and
      measurement of hemoglobin AIC and renal function. RESULTS: Overall, compliance
      with recommendations for diabetes management increased from a baseline proportion
      of 40% to a level of 70% at the end of 1 year. During the second year, overall
      compliance was maintained at this level despite the inclusion of additional
      performance indicators. CONCLUSIONS: The CQI process can improve physician
      performance in managing patients with diabetes.

PMID- 9624525
TI  - Challenges for family medicine.

PMID- 9624526
TI  - The birth of the blended curriculum.
AB  - BACKGROUND AND OBJECTIVES: In the struggle to survive economically, our family
      practice residency program developed a new curriculum that incorporated elements
      of both the conventional rotational model and the newer longitudinal mode. We
      also created unique elements: immersion weeks, subspecialty clinics, and Tuesday
      specials. Immersions weeks provide focused exposures to specialty areas. The
      resident brings learned skills back to the family practice clinic (FPC).
      Subspecialty clinics in the FPC bring specialists to the residents and to the
      residents' patients for reinforcement of learned skills. Tuesday specials provide
      longitudinal experiences in geriatric, community, and occupational medicine. The
      blended curriculum has been a success with both Residency Assistance Program
      consultants and the Residency Review Committee reviewer. It has also increased
      residents' availability to see patients in the FPC and increased FPC income.

PMID- 9624527
TI  - Identification of allelic loss on chromosome arm 6p in human astrocytomas by
      arbitrarily primed polymerase chain reaction.
AB  - We employed the arbitrarily primed polymerase chain reaction (AP-PCR), which is a
      PCR-based genomic fingerprinting technique, to detect novel genetic alterations
      in human astrocytomas. DNA fingerprints generated by arbitrary primers were
      compared in normal lymphocytes and tumor tissues from the same individuals. We
      cloned and sequenced an AP-PCR band showing a greatly decreased intensity in
      tumor tissue DNA, relative to normal. Southern blot showed that this sequence was
      homozygously deleted in the tumor cell genome. Semiquantitative PCR analysis
      further showed significant decreases of signals in seven of 24 tumors, consistent
      with homozygous deletion of this sequence. The deleted sequence was localized to
      chromosome region 6p21.1 by the fluorescence in situ hybridization method.
      Microsatellite analysis also showed frequent allelic loss of this locus compared
      to neighboring loci in astrocytoma tissues. These results suggest the presence of
      a novel tumor suppressor gene at the 6p21.1 locus.

PMID- 9624528
TI  - Overrepresentation of 7q31 and 17q in renal cell carcinomas.
AB  - Xenografts from four metastatic renal cell carcinomas (RCCs) were established in
      immunodeficient mice. All tumors exhibited cytogenetic features specific for the
      papillary subtype, namely, partial or total polysomy of chromosomes 7 and 17 and
      integrity of 3p. Cytogenetic analysis of the initial and xenografted tumors
      indicated that although clonal characteristics were consistently maintained in
      xenografts derived from metastases, a minor clone had been selected for in the
      xenografts derived from the primary tumors. Reverse painting and comparative
      genomic hybridization (CGH) allowed us to localize minimal overrepresented
      genomic regions to 7q31, where the MET protooncogene is located, and to 17q.
      Other overrepresented regions were 8q in all xenografts and Xq22-qter in three of
      them. The gain of genetic material from these regions may be a key factor
      ensuring the papillary nature of RCCs and their survival in xenografts.

PMID- 9624529
TI  - Isolation and characterization of a novel human pancreas-specific gene, pancpin,
      that is down-regulated in pancreatic cancer cells.
AB  - By means of the differential display method, we isolated a novel human gene that
      is expressed specifically in pancreas. The cDNA, designated "pancpin," contained
      an open reading frame of 1,215 nucleotides encoding a 405 amino acid protein,
      showing a high degree of similarity to serine protease inhibitors belonging to
      the serpin superfamily. To investigate its possible role in pancreatic
      carcinogenesis, we looked for genetic alterations of this gene in pancreatic
      cancer cell lines and primary pancreatic cancer tissues. Expression of pancpin
      was barely detectable in any of the four pancreatic cancer cell lines examined,
      and very weak also in 10 of 13 pancreatic cancer tissues. A somatic missense
      mutation at codon 221 was found in two of 16 primary pancreatic cancers. These
      findings indicate that down-regulation of pancpin expression may play a
      significant role in development or progression of pancreatic cancer.

PMID- 9624530
TI  - Chromosome region 8p11-p21: refined mapping and molecular alterations in breast
      cancer.
AB  - Several genes, most of them unknown, of the short arm of chromosome 8 are
      involved in malignant diseases. Numerous studies have implicated a portion of the
      8p11-p21 region as the location of one or more tumor suppressor genes involved in
      a variety of human cancers, including breast cancer. We and others have reported
      linkage analyses suggesting the presence of a putative breast cancer
      susceptibility gene. Furthermore, several oncogenes of the 8p11-p12 region are
      involved in reciprocal translocations in myeloproliferative and myelodysplastic
      disorders and in amplification in breast cancer. To facilitate the analysis of
      the 8p11-p21 region and the cloning of candidate oncogenes and tumor suppressor
      genes, a high-resolution physical and transcriptional map was established with 39
      yeast artificial chromosomes and 94 markers, including so-called sequence-tagged
      sites and expressed sequence-tagged sites derived from either known genes or
      expressed sequence tags corresponding to unidentified transcripts. In addition,
      four novel transcripts were identified and localized precisely within the map.
      This transcription map provides a detailed description of gene order for the 8p11
      p21 region and will be helpful in the identification of candidate genes for
      diseases. From this basis, we refined the mapping of two types of molecular
      alterations that occur at 8p11-p21 in sporadic breast cancers, i.e.,
      amplification and deletion.

PMID- 9624531
TI  - Inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene and allelic
      losses at chromosome arm 3p in primary renal cell carcinoma: evidence for a VHL
      independent pathway in clear cell renal tumourigenesis.
AB  - Inactivation of tumour suppressor gene(s) (TSGs) on 3p appears to be a critical
      event in the pathogenesis of clear cell renal cell carcinoma (CC-RCC). Analysis
      of loss of heterozygosity (LOH) in sporadic RCC samples has implicated roles for
      TSGs in three specific regions of 3p in RCC development: (1) 3p12-p14, which
      includes the breakpoint of the familial t(3;8) constitutional translocation
      involved in hereditary RCC development and a recently cloned putative TSG, the
      FHIT gene: (2) 3p21.2-p21.3, a common region of deletion in many cancers
      including lung; and (3) 3p25-p26, which contains the von Hippel-Lindau (VHL)
      disease TSG. We and others have shown that most primary sporadic CC-RCCs contain
      somatic VHL gene mutations, clearly implicating inactivation of the VHL gene in
      the pathogenesis of CC-RCC. It is not known if CC-RCC without VHL gene mutations
      have alternative mechanisms of VHL gene inactivation or result from an
      alternative non-VHL pathway to RCC, e.g., inactivation of TSGs in 3p12-p21. We
      and others have reported hypermethylation and silencing of the VHL TSG in RCC
      from patients with VHL disease and in CC-RCC cell lines. However, the incidence
      and specificity of VHL methylation in primary sporadic RCC has not been defined.
      Therefore, we analysed methylation of the VHL, CDKN2, MYC, and H19 genes in
      primary RCC samples. Hypermethylation of the VHL promoter region was detected in
      11% (11/99) of the primary RCCs analysed. In 10 of these tumours, there was no
      evidence of concomitant VHL gene mutation. VHL methylation was specific to CC-RCC
      (15%, 7/45) but was not detected in any non-CC tumours (n = 16). None of the 11
      RCCs methylated at VHL had evidence of methylation at either CDKN2 or MYC
      (methylation at CDKN2 was, however, detected in 3%, or 1/33, of RCCs without VHL
      methylation). A normal methylation pattern at H19 was demonstrated in the three
      RCCs with methylated VHL analysed. Previous studies have suggested that, in
      addition to VHL, other 3p TSGs at 3p12-p14 and 3p21 may be involved in CC-RCC
      tumourigenesis. However, the interpretation of these studies has been difficult
      because information on VHL gene status has not been available for these data
      sets. Therefore, we investigated a subset of 55 sporadic RCCs (of known VHL gene
      methylation and mutation status) for LOH at polymorphic markers close to
      candidate TSG loci in the 3p14.2 and 3p21.2-p21.3 regions. Among tumours with LOH
      at one or more 3p markers, the incidence of 3p25 allele loss was higher in
      tumours with VHL alterations (mutation or methylation) than in those without. For
      tumours without detectable VHL alterations, the frequency of 3p14-p21 LOH was
      significantly higher than the frequency of 3p25-p26 LOH (93%, 13/14 vs. 43%,
      6/14; P = 0.013), whereas, in RCC samples with VHL methylation or mutation, the
      frequency of 3p14-p21 LOH did not differ from that of sp25-p26 (72%, 18/25 vs.
      59%, 13/22; P = 0.376). None of the 11 RCCs with 3p25 allele loss that were
      informative at 3p21 and 3p14 showed LOH at 3p25 only. These findings suggest that
      (1) VHL methylation is a specific and important event in the pathogenesis of CC
      RCC; (2) in CC-RCC with 3p LOH but without VHL inactivation, mutations in TSGs at
      3p14-p21 appear to have a primary role in tumourigenesis; and (3) inactivation of
      other 3p TSGs in addition to VHL may also be required for malignant
      transformation in tumours with VHL gene inactivation.

PMID- 9624532
TI  - Localization of a CDKN2 gene in linkage group V of Xiphophorus fishes defines it
      as a candidate for the DIFF tumor suppressor.
AB  - The Xiphophorus hybrid melanoma model represents one of the earliest reported
      cases of genetically regulated tumor susceptibility. Melanoma formation in
      Xiphophorus hybrids may be explained by the inheritance of two genes: a sex
      linked oncogene, Xmrk, and a putative tumor suppressor locus, termed DIFF,
      located in Linkage Group V (LG V). Several genetic mapping procedures were used
      to produce a new Xiphophorus LG V map with 20 loci. All markers, particularly a
      recently cloned Xiphophorus CDKN2 gene family member, called CDKN2X, were tested
      for associations of genotype with degree of macromelanophore pigment pattern
      modification and susceptibility to melanoma formation in backcross hybrids of
      seven genetic types, involving 1,110 fish and three pigment patterns. Highly
      significant associations of CDKN2X genotypes with such phenotypic effects
      suggests that this gene is a strong candidate for the classically defined DIFF
      tumor suppressor gene. Because published results have documented the involvement
      of the CDKN2A (p16, MTS1, and INK4A) tumor suppressor gene in human melanoma
      formation, the possibility of CDKN2 genes acting as tumor suppressors in both man
      and Xiphophorus is likely.

PMID- 9624533
TI  - A new case of translocation t(6;11)(q21;q23) in a therapy-related acute myeloid
      leukemia resulting in an MLL-AF6q21 fusion.
AB  - A new case of translocation t(6;11)(q21;q23) in a patient with therapy-related
      acute myeloblastic leukemia is reported. The translocation results in fusion of
      the MLL and AF6q21 genes. The breakpoint with AF6q21 is located within the
      sequences encoding the AF6q21 fork head motif. The similar location of the
      localization of the chromosome 6 breakpoints in the present case and in the first
      case reported suggests their nonrandom localization. In addition, treatment for
      Hodgkin's disease prior to leukemia in both t(6;11)(q21;q23) cases suggests an
      association of this translocation with therapy-related leukemias, as reported for
      the recently described.

PMID- 9624534
TI  - Temporal differences in replication timing of homologous loci in malignant cells
      derived from CML and lymphoma patients.
AB  - A close association usually exists between replication timing of a given locus
      and its transcriptional activity: expressed loci replicate early whereas silent
      ones replicate late. Accordingly, alleles that show concomitant expression
      replicate synchronously, while those displaying an allele-specific mode of
      expression show temporal differences in their replication timing, i.e., they
      replicate asynchronously. We aimed in our study to see whether the cancer
      phenotype is accompanied by a relaxation in the temporal control of allelic
      replication. Fluorescence in situ hybridization (FISH) was used to determine the
      level of synchronization in replication timing of four pairs of homologous loci
      in samples of malignant cells derived from patients with chronic myeloid leukemia
      (CML) and lymphoma and in samples from healthy individuals. Four loci, HER2
      mapped to 17q11.2-q12, a locus at 21q22, TP53 mapped to 17q13.1, and MYC mapped
      to 8q24 were studied. In each sample we analyzed two chromosomal regions, either
      17q11.2-q12 and 21q22 or 17p13.1 and 8q24. The results showed distinct
      differences between healthy individuals and CML/lymphoma patients: all samples
      derived from noncancerous subjects showed high levels of synchrony in replication
      timing of alleles, whereas those of cancer patients displayed a large temporal
      difference in replication timing, indicating early and late replicating alleles.
      Thus, as judged by four unrelated loci, malignancy is associated with changes in
      the replication pattern of homologous loci.

PMID- 9624535
TI  - Association of CDKN2A(p16)/CDKN2B(p15) alterations and homozygous chromosome arm
      9p deletions in human lung carcinoma.
AB  - To elucidate the possibility of the existence of multiple tumor suppressor genes
      on chromosome arm 9p, we performed genetic and epigenetic analyses of the
      CDKN2A/p16/MTS1 and CDKN2B/p15/MTS2 genes as well as homozygous deletion mapping
      of 9p in human lung carcinoma. To avoid overlooking genetic alterations due to
      contamination of noncancerous cells, we examined 32 non-small cell lung carcinoma
      (NSCLC) and 16 cell small cell lung carcinoma (SCLC) cell lines. (CDKN2A was
      mutated or homozygously deleted in 20 (63%) of 32 NSCLC cell lines, and
      methylation of the CpG island in the CDKN2A gene was detected in six of the 12
      cell lines carrying the wild-type CDKN2A gene. Although homozygous deletions of
      the CDKN2B gene were also detected in NSCLC cell lines with CDKN2A deletions,
      mutation and methylation in the CDKN2B gene were infrequent. Thus, it was
      indicated that the CDKN2A gene rather than the CDKN2B gene plays a critical role
      as a tumor suppressor gene in NSCLC. Homozygous deletions on 9p were detected in
      14 (44%) NSCLC cell lines. It is of note that two common regions of homozygous
      deletions were mapped proximal to the CDKN2A and CDKN2B loci, suggesting that
      tumor suppressor genes other than CDKN2A are present on 9p. In contrast to NSCLC,
      homozygous deletions on 9p as well as CDKN2A and CDKN2B alterations were
      infrequent in SCLC. Therefore, the pathogenetic significance of 9p alterations is
      likely to differ between SCLC and NSCLC.

PMID- 9624537
TI  - Molecular cytogenetic delineation of the critical deleted region in the 5q-
      syndrome.
AB  - The 5q- syndrome is a distinct type of myelodysplastic syndrome (MDS)
      characterised by refractory anaemia, morphological abnormalities of
      megakaryocytes, and del(5q) as the sole cytogenetic abnormality. In contrast to
      patients with therapy-related MDS with 5q deletions, 5q- syndrome patients have a
      favourable prognosis and a low rate of transformation to acute leukaemia. We have
      previously delineated a common deleted region of 5.6 Mb between the gene for
      fibroblast growth factor acidic (FGF1) and the subunit of interleukin 12 (IL12B)
      in two patients with 5q- syndrome and small deletions, del(5)(q31q33). The
      present study used fluorescence in situ hybridisation (FISH) analysis of these
      and a third 5q- syndrome patient with a small deletion, del(5)(q33q34), to refine
      further the critical deleted region. This resulted in the narrowing of the common
      deleted region within 5q31.3-5q33 to approximately 3 Mb, flanked by the
      adrenergic receptor beta 2 (ADRB2) and IL/2B genes. The common region of loss in
      these three 5q- syndrome patients includes the macrophage colony-stimulating
      factor-1 receptor (CSF1R), secreted protein, acidic, cysteine-rich (SPARC), and
      glutamate receptor (GR1A1) genes. This 5q- syndrome critical region is telomeric
      to and distinct from the other critical regions on 5q associated with MDS and
      acute myeloid leukaemia.

PMID- 9624536
TI  - In vitro response to all-trans retinoic acid of acute promyelocytic leukemias
      with nonreciprocal PML/RARA or RARA/PML fusion genes.
AB  - Acute promyelocytic leukemia (APL) is characterized by the t(15;17) cytogenetic
      abnormality leading to the expression of two fusion genes, PML/RARA and RARA/PML,
      and by its sensitivity to all-trans retinoic acid (ATRA) differentiating
      treatment. Rare APL cases lacking the t(15;17) have been described. We have
      previously reported two cases presenting with submicroscopic insertions of RARA
      or PML into chromosome 15 or 17, respectively. These insertions lead to the
      formation of potentially functional, nonreciprocal, PML/RARA or RARA/PML fusion
      genes, providing the unique opportunity to investigate in a human noncell-line
      model the respective role of PML/RARA or RARA/PML in retinoid signaling. Here, we
      report the in vitro response to ATRA of these two cases as well as of a third
      case presenting with submicroscopic insertion (15;17) and expressing exclusively
      PML/RARA, by morphological, functional, and immunological assays. The two cases
      expressing PML/RARA presented with an immunostaining pattern typical of APL and a
      positive response to ATRA, whereas the APL case expressing only a RARA/PML fusion
      transcript exhibited an immunostaining pattern typical of non-APL cells, and was
      resistant to ATRA. Our results confirm that sensitivity to ATRA requires
      expression of PML/RARA and strongly correlates with immunostaining, and
      demonstrate that expression of RARA/PML alone is sufficient for a cytological APL
      phenotype, but does not confer sensitivity to ATRA.

PMID- 9624538
TI  - Colony-stimulating factors in the prevention of solid tumors induced by
      chemotherapy in patients with febrile neutropenia.
AB  - Haematologic toxicity and its most frequent complication, febrile neutropenia
      represents the main limiting factor to the use of anti-cancer chemotherapy. The
      recent availability of recombinant human colony stimulating factors offers a new
      opportunity to improve the tolerance of these treatments. Most randomized trials
      in various solid tumors have demonstrated the ability of granulocyte colony
      stimulating factor and granulocyte-macrophage colony-stimulating factor to
      significantly reduce the incidence of febrile neutropenia and related
      complications. Interestingly enough, these compounds are well tolerated and easy
      to administrate. However, since the increase in dose-intensity does not translate
      into any improved efficacy in terms of response rates or survival, the use of
      colony-stimulating factors has to be decided on the basis of cost-benefit
      considerations. Therefore, some scientific societies such as the American
      Association of Clinical Oncology in the US and the Anti-Cancer Centers Group in
      France have published recommendations for their use in routine oncology practice.
      We here discuss these guidelines on the basis of an overview of the literature.

PMID- 9624539
TI  - Antibacterial agents--phagocytes: new concepts for old in immunomodulation.
AB  - The possibility that antibacterial agents, primarily directed against
      microorganisms, also modify host functions is widely recognized. While a
      knowledge of these non-antimicrobial effects of antibiotics, sometimes considered
      as 'side-effects', is necessary to prevent antibiotic-associated toxicity, the
      development of drugs derived from antibacterial agents for use in non-infectious
      diseases (e.g. motilins and antidiabetic drugs) is a new field of therapeutic
      research. Interactions between antibacterial drugs and the immune system may
      contribute to therapeutic efficacy in infectious diseases [1,2]. The immune
      system itself is a complex pyramid of redundant cellular factors/humoral
      effectors/mediators, whose fine regulation is just beginning to be unraveled.
      Phagocytes, ubiquitous and multifaceted cells are key components of cellular
      immunity, being involved both in immediate defences against non-self targets
      (pathogens, tumour cells, exogenous molecules, etc.) and in the regulation and
      triggering of specific immune responses. They are thus, prime targets of immune
      response modifiers. This review reconsiders the widely explored problem of
      interactions between antibacterial agents and phagocytes, focusing on future
      prospects in both infectious and non-infectious diseases.

PMID- 9624540
TI  - In vitro activity of BAY 12-8039, a new fluoroquinolone, against species
      representative of respiratory tract pathogens.
AB  - The in vitro antibacterial activity of BAY 12-8039, a novel 8-methoxy-quinolone,
      was compared with those of other quinolones, amoxicillin/clavulanate, cefuroxime
      and erythromycin against species commonly implicated in respiratory tract
      infections as well as viridans group streptococci. The new compound was highly
      active against methicillin-susceptible staphylococci (MIC90 0.125 microgram/ml),
      penicillin-susceptible and penicillin-resistant pneumococci (MIC90 0.5 and MIC50
      0.25 microgram/ml, respectively), penicillin-susceptible and penicillin-resistant
      viridans group streptococci (MIC90 0.5 and 0.25 microgram/ml, respectively),
      group A streptococci (MIC90 0.25 microgram/ml), M. catarrhalis (MIC90 0.125
      microgram/ml) and H. influenzae (MIC90 0.063 microgram/ml), irrespective of beta
      lactamase production. It was, however, less active against methicillin-resistant
      staphylococci (MIC50 and MIC90, 2 and 4 micrograms/ml, respectively). The new
      compound demonstrated bactericidal activity at concentrations 2, 4, 8 times the
      MIC against representative isolates of the above collection. At a concentration
      of eight times the MIC, the frequency of spontaneous resistance ranged from 2.5 x
      10(-7) to < 4 x 10(-8). These results suggested that BAY 12-8039 would be a
      promising agent for the eradication of respiratory tract pathogens and that
      clinical trials assessing its efficacy for the management of infections caused by
      these organisms are warranted.

PMID- 9624541
TI  - Urinary bactericidal activity and pharmacokinetics of enoxacin versus norfloxacin
      and ciprofloxacin in healthy volunteers after a single oral dose.
AB  - In an open, randomised monocentric crossover study in six male and six female
      healthy volunteers, the urinary antibacterial activity and pharmacokinetics of
      enoxacin, norfloxacin and ciprofloxacin were assessed. Urine was collected up to
      6 days, and venous blood samples up to 12 h, after a single oral dose of 400 mg
      enoxacin, 400 mg norfloxacin and 500 mg ciprofloxacin. Enoxacin (250 mg/l)
      demonstrated the highest peak concentration (median) in the urine (0-6 h),
      followed by ciprofloxacin (237 mg/l) and norfloxacin (157 mg/l) as determined by
      the HPLC assay. The total amount (mean) excreted by the kidneys as parent drugs
      were as follows: enoxacin 54% of dose, ciprofloxacin 33% of dose, and norfloxacin
      22% of dose. The mean plasma concentrations decreased from 1 to 4 h after
      administration for enoxacin from 1.9 to 1.4 mg/l, for ciprofloxacin from 2.0 to
      0.8 mg/l and for norfloxacin from 1.3 to 0.5 mg/l. The antibacterial activity in
      urine was determined as urinary bactericidal titers (UBT), i.e. the highest 2
      fold dilution of urine still bactericidal for the reference organism (E. coli
      ATCC 25,922) and for five uropathogens with minimal inhibitory (MIC) and
      bactericidal (MBC) concentrations ranging from highly susceptible to resistant
      cultured from the urine of patients with complicated urinary tract infections
      (UTI). For the E. coli ATCC 25,922, the organism with the lowest MIC, median UBTs
      of ciprofloxacin were present for 4 days, decreasing from 1:512 to 1:2, that of
      enoxacin for 2 days, decreasing from 1:256 to 1:4, and that of norfloxacin for 2
      days, decreasing from 1:128 to 1:2. For the five uropathogens (with increasing
      MICs: K. pneumoniae, P. mirabilis, E. coli (resistant to nalidixic acid), P.
      aeruginosa and E. faecalis), the UBTs decreased in general, according to MICs,
      demonstrating the same relations of UBTs for ciprofloxacin (highest) versus
      enoxacin (medium) versus norfloxacin (lowest) with one exception (P. mirabilis)
      for which norfloxacin showed higher UBTs than enoxacin. The minimal urinary
      bactericidal concentrations (MUBC), as derived from urinary concentrations, and
      UBTs showed a fairly wide inter- and intraindividual range and were generally
      higher than the corresponding MBCs as determined in Mueller Hinton broth. In
      conclusion, according to antibacterial activity in urine determined as UBTs, a
      single oral dose of ciprofloxacin (500 mg) generally resulted in the highest and
      longest-lasting UBTs followed by that of enoxacin (400 mg) and norfloxacin (400
      mg). A dose of 400 mg enoxacin can be expected to be at least equivalent if not
      superior to that of 400 mg norfloxacin. Only enoxacin and ciprofloxacin exhibited
      urinary bactericidal activity against all test organisms up to 12 h in all
      individuals. Therefore, clinical comparison of enoxacin versus ciprofloxacin in
      the treatment of complicated UTI could be worth testing.

PMID- 9624542
TI  - A comparison between single-dose fosfomycin trometamol (Monuril) and a 5-day
      course of trimethoprim in the treatment of uncomplicated lower urinary tract
      infection in women.
AB  - This study is a comparison of the microbiological and clinical efficacy of single
      dose fosfomycin trometamol therapy and a 5 day course of trimethoprim in the
      treatment of uncomplicated urinary tract infection in female patients. Urine dip
      slide samples were obtained from 547 female patients aged 18-65 by 22 General
      Practitioners (GPs) participating in the study from 21 centres in the UK. All
      patients were diagnosed as having a urinary tract infection by their GP on the
      basis of history and clinical examination. Patients were randomised to receive
      either single dose fosfomycin trometamol or a 5 day course of trimethoprim in a
      2:1 ratio. Patients who had significant bacteriuria (> or = 10(5) c.f.u/ml) at
      the first visit (300) were included in the microbiological analysis. The two
      commonest urinary pathogens isolated were Escherichia coli and Staphylococcus
      saprophyticus. Trimethoprim resistance was more frequent amongst E. coli isolates
      whereas fosfomycin trometamol resistance was more common amongst S. saprophyticus
      isolates. Microbiological cure was demonstrated in 83.3% of the trimethoprim
      treated group and 83% of the fosfomycin trometamol treated group. Persistence of
      the infecting bacteria was seen in 17% of each treatment arm.

PMID- 9624543
TI  - Comparison of the efficacy and safety of a short course of ceftibuten with that
      of amoxycillin/clavulanate in the treatment of acute exacerbations of chronic
      bronchitis.
AB  - The efficay and safety of short course ceftibuten (400 mg od for 5 days; n = 163)
      were compared with that of amoxycillin/clavulanate (AMX/CA) (250/125 mg tds for
      10 days; n = 172) in a multicentre, single-blind, parallel-group trial in 335
      adults with acute exacerbations of chronic bronchitis (AECB). Clinical response
      was equivalent, with cure or improvement in 134/145 (92.4%) ceftibuten-treated
      patients and 139/150 (92.7%) AMX/CA-treated patients (95% CI: -7.00%, +6.50%).
      The overall eradication rates were similar (ceftibuten 88.3%; AMX/CA 87.5%) and
      also the incidence of adverse events which occurred in 24/163 (14.7%) ceftibuten
      treated and 27/172 (15.5%) AMX/CA-treated patients. Ceftibuten 400 mg od for 5
      days is as effective and well tolerated as AMX/CA 250 mg tds for 10 days in the
      treatment of AECB.

PMID- 9624544
TI  - Bacteremia due to methicillin-resistant staphylococci occurs more frequently in
      neutropenic patients who received antimicrobial prophylaxis and is associated
      with higher mortality in comparison to methicillin-sensitive bacteriemia.
AB  - Bacteriemia due to coagulase-negative staphylococci (CNS) resistant to
      methicillin and sensitive only to glycopeptides in 220 cancer patients was
      prospectively analyzed for risk factors and outcome. A group of 33 cases of
      bacteriemia with CNS-sensitive only to glycopeptides was compared with a group of
      187 cases with CNS sensitive to methicillin. All cases appeared in two affiliated
      major cancer institutes in Bratislava with the same antibiotic policy. Univariate
      analysis showed differences in recorded risk factors: acute leukemia (48 vs. 33%,
      P < 0.05), neutropenia (57 vs. 32%, P < 0.045), previous prophylaxis with
      quinolones (30 vs. 11%, P < 0.01) and penicillin-V (15 vs. 3%, P < 0.02) and
      previous colonisation with CNS (27 vs. 3%, P < 0.01) were more frequently
      associated with bacteriemia resistant to methicillin and sensitive only to
      glycopeptides. Attributable mortality was also higher in this subgroup in
      comparison to bacteriemias with CNS sensitive to methicillin (12 vs. 3%, P <
      0.05) however, overall mortality was similar. Bacteriemias due to CNS caused by
      sensitivity only to glycopeptides occurred more frequently in neutropenic
      patients (1), with acute leukemia (2), receiving quinolone and penicillin
      prophylaxis (3), and previously colonized (4), patients and had worse prognosis
      in comparison to those with methicillin-sensitive staphylococcal bacteriemias.

PMID- 9624545
TI  - Evaluation of in vivo therapeutic efficacy of a new benzoxazinorifamycin, KRM
      1648, in SCID mouse model for disseminated Mycobacterium avium complex infection.
AB  - In this study, profiles of infection due to Mycobacterium avium complex (MAC) in
      CB-17 SCID mice deficient in T and B cell functions were examined, when mice were
      given or not given a new benzoxazinorifamycin, KRM-1648 (KRM), during the course
      of infection. When mice were infected intravenously with MAC, the bacterial loads
      in their visceral organs were larger than those of their co-isogenic CB-17
      counterparts. The incidence and the degree of gross lung lesions were less in
      SCID mice compared to CB-17 mice. Athymic BALB/c nude mice showed similar
      profiles of the infection. Beige mice showed more severe gross lesions and larger
      bacterial loads in the lungs than did SCID and athymic BALB/c nude mice. When MAC
      was infected subcutaneously into the hind footpads of mice, disseminated growth
      of organisms in the footpads, blood, and visceral organs was seen in SCID mice,
      but not in CB-17 or BALB/c mice. KRM exhibited the same level of therapeutic
      effect on SCID mice infected with MAC via the intravenous route in terms of
      inhibiting bacterial growth in the lungs and kidneys, as in cases of CB-17 and
      BALB/c mice with normal T-cell functions. In beige mice, the degree of growth
      inhibition of MAC due to KRM treatment was significantly greater than that
      achieved in SCID mice.

PMID- 9624546
TI  - In vitro anti-Junin virus activity of a peptide isolated from Melia azedarach L.
      leaves.
AB  - Meliacine, a peptide isolated from leaves of Melia azedarach L. inhibited the
      multiplication of Junin virus in Vero cells treated with the compound before
      infection (pre-treatment) or immediately after virus adsorption. Analysis of
      early events following infection demonstrated that meliacine blocks virus
      penetration by preventing the uncoating step. The addition of meliacine at
      different times after infection indicated that meliacine also interferes with the
      release of infectious particles to the extracellular medium and inhibits the low
      pH-induced fusion of infected cells. Intracellular transport of viral
      glycoproteins to the cell membrane was not affected by meliacine, as revealed by
      immunofluorescence staining. Taken together, these results suggest that meliacine
      affects two events of the virus replicative cycle that require membrane fusion:
      uncoating and budding.

PMID- 9624547
TI  - Antibiotic resistance of pneumococci in Norway.
AB  - A collection of 178 pneumococcal isolates found in Norway during the period 1987
      1994 were tested for their susceptibility to benzylpenicillin, macrolides
      (azithromycin, clarithromycin, dirithromycin, erythromycin, roxithromycin,
      spiramycin), fluoroquinolones (ciprofloxacin, sparfloxacin), imipenem,
      chloramphenicol, and vancomycin by a standard agar dilution procedure. To
      benzylpenicillin, two strains (1%) showed resistance and 14 strains (8%)
      intermediate susceptibility. Towards erythromycin, eight strains (4%) showed
      resistance and four strains (2%) intermediate susceptibility. Cross-resistance
      was demonstrated among the macrolides. Among the fluoroquinolones, intermediate
      susceptibility occurred with 42% of the isolates for sparfioxacin and 90% for
      ciprofloxacin; to the latter 5.1% proved resistant. The sum of intermediate and
      highly resistant isolates was 53% for chloramphenicol. Both penicillin-resistant
      strains were isolated during the last 2 years of collection and came from
      patients of non-Norwegian ethnic background. Imported strains appeared over
      represented among the strains resistant to penicillin and macrolides. Only
      imipenem and vancomycin showed full susceptibility for all pneumococci tested. An
      over representation of serogroup 6 strains was apparent among the strains with
      intermediate susceptibility and high resistance to benzylpenicillin. It is
      apparent that high-level resistance has, not so far, become a difficult problem
      in Norway. Nevertheless, the situation requires monitoring of the resistance
      level, particularly in meningitis and septic patients, and certainly in patients
      who cntail a higher than usual possibility of acquiring pneumococci from pools of
      resistant strains outside Norway (visitors, immigrants and recent returness from
      abroad).

PMID- 9624548
TI  - Antimicrobial activity of antiseptic-coated orthopaedic devices.
AB  - Antimicrobial coating of medical devices, including fracture fixation devices,
      has evolved as a potentially effective method for preventing device-related
      infections. We examined the in vitro antimicrobial activity of titanium cylinders
      coated with the antiseptic combination of chlorhexidine and chloroxylenol. The
      coated devices provided zones of inhibition against Staphylococcus epidermidis,
      S. aureus, Pseudomonas aeruginosa, Escherichia coli and Candida albicans, at
      baseline and up to 8 weeks after incubation of the coated cylinders in human
      serum at 37 degrees C. This durable antimicrobial activity was attributed to the
      relatively slow leaching of chlorhexidine and chloroxylenol from the coated
      cylinders as measured by high-performance liquid chromatography. These results
      suggest that antiseptic-coated orthopaedic devices may provide broad-spectrum and
      durable antimicrobial protection against device-related infection.

PMID- 9624549
TI  - Possible relationship between dietary factors and pathogenesis of prostate
      cancer.

PMID- 9624550
TI  - Assessment of proliferating cell nuclear antigen expression and prognosis in
      patients with renal cell carcinoma with pulmonary metastases.
AB  - BACKGROUND: The presence of proliferating cell nuclear antigen (PCNA) has been
      suggested as a more important prognostic marker than either grade or mitotic
      index in the prognosis of patients with renal cell carcinoma. We assessed the
      immunoreactivity of PCNA in primary lesions and pulmonary metastases from
      patients with renal cell carcinoma and correlated the results with various
      histopathologic features and prognostic factors. METHODS: We studied the
      relationship between PCNA expression and clinical prognostic factors from
      resected primary lesions and pulmonary metastases from 10 patients and primary
      lesions from 32 patients with renal cell carcinoma without metastases. The cells
      were immunohistochemically stained with PCNA monoclonal antibody (PC-10) and 1000
      nuclei were counted. The results were expressed as a ratio of stained to total
      cells (PCNA labeling index, LI %). RESULTS: The PCNA LI of pulmonary metastatic
      nuclei was significantly higher than the PCNA LI of renal lesions either from
      patients with (P < 0.05) or without (P < 0.01) metastases. Also, the mean PCNA LI
      of the pulmonary lesions in patients dying within 3 years of diagnosis was higher
      than the mean PCNA LI of patients surviving greater than 3 years. CONCLUSION: Our
      findings suggest that the PCNA LI, which was determined by immunohistochemical
      analysis, is an important marker reflecting the biologic behavior of renal cell
      carcinomas. The degree of PCNA expression in this study was of prognostic
      significance.

PMID- 9624551
TI  - Ileal neobladder for bladder substitution after radical cystectomy.
AB  - BACKGROUND: Studer's ileal neobladder is technically simple, and favorable
      clinical results have been reported. However, there have been only a few follow
      up studies on this type of ileal neobladder. We reviewed the clinical outcomes of
      patients who received Studer's ileal neobladder, with a minor modification, in
      our institution. METHODS: Twenty-five men underwent bladder reconstruction with
      Studer's ileal neobladder after radical cystectomy. The function of the ileal
      neobladder and voiding status were evaluated during follow-up. The follow-up
      period ranged from 3 to 42 months (mean, 24 months). RESULTS: The ileal
      neobladder achieved a large capacity at a low basal pressure, associated with a
      relatively low complication rate directly related to the neobladder. At 12 months
      after surgery, daytime and nighttime continence rates were 90% and 74%,
      respectively. In 5 patients who were incontinent, the maximal urethral closure
      pressure was statistically lower than in patients with continence. CONCLUSION:
      Studer's ileal neobladder is an easy operative procedure for bladder
      substitution, and has a relatively low complication rate directly related to the
      neobladder. Good compliance of the pouch and preservation of the external
      sphincter mechanism are the most important factors for achieving urinary
      continence, after construction of the ileal neobladder.

PMID- 9624552
TI  - Preliminary results of bladder preservation by concurrent intraarterial
      chemotherapy and radiotherapy for muscle-invasive bladder cancer.
AB  - BACKGROUND: We previously reported favorable results of intraarterial doxorubicin
      chemotherapy in combination with low-dose radiotherapy for locally-advanced
      bladder cancer. We have now designed a new intraarterial chemotherapy regimen to
      achieve a higher tumor response rate while preserving a functional bladder.
      METHODS: Twenty-one patients with muscle-invasive bladder cancer (T2,10; T3,7;
      T4,4) were treated with concurrent intraarterial chemotherapy and radiotherapy
      after an initial complete transurethral resection. Induction therapy consisted of
      concomitant pirarubicin (THP; 15 mg/m2/day on days 1 to 3), cisplatin (CDDP; 25
      mg/m2/day on days 8 to 10) and irradiation (2 Gy/session on days 1 to 3 and 8 to
      10). Maintenance treatment consisted of THP administered at 20 or 30 mg with or
      without 50 mg CDDP every month for 2 years. RESULTS: Nineteen of the 21 patients
      (90.5%) achieved a complete response (CR). One of these 19 relapsed with lung
      metastases 24 months after treatment and was treated surgically. The 2 patients
      who did not achieve a CR died of cancer, while the remaining 19 patients are
      alive with preservation of a functional bladder. CONCLUSION: These findings
      suggest that a higher tumor response rate with bladder preservation for patients
      with muscle-invasive bladder cancer is achieved by intraarterial THP/CDDP
      chemotherapy plus radiotherapy.

PMID- 9624553
TI  - Antitumor killer lymphocytes in the peripheral blood of a patient with
      transitional cell carcinoma of the bladder.
AB  - BACKGROUND: Peripheral blood lymphocytes (PBL) from patients with bladder cancer
      also contain cells possessing cytotoxic activity against autologous tumor cells.
      These cells are phenotypically heterogenous and include natural killer (NK) and
      cytotoxic T cells. This study investigated the role of cytotoxic lymphocytes
      directed against autologous bladder cancer cells. METHODS: PBL were obtained at
      intervals before and after surgery and analyzed for cytotoxic activity against
      autologous bladder cancer cells in 4-hour 51Cr release assay. PBL stimulated with
      autologous tumor cells were also transformed with human T-lymphotropic virus type
      1, establishing a cell line (KB31) which was analyzed for phenotype and cytotoxic
      activity against the autologous tumor cells. RESULTS: PBL preoperative cytotoxic
      activity was low, but increased after surgery. Cytotoxic activity was found not
      only against autologous bladder cancer cells, but also against heterologous
      bladder cancer (KK-47) and myeloid leukemia (K562) cells, with the highest
      activity against the heterologous cell lines. The cytotoxic activity of KB31 was
      40% against autologous tumor cells 6 weeks after initiation of the cell line, but
      decreased to 5% by 6 months. This activity was lower than that against the other
      cell lines, and was similar to that of PBL in short-term culture. Fluorescence
      activated cell sorter (FACS) analysis demonstrated that in KB31 cells at 6 weeks,
      CD8+ cells were dominant, but CD56+ cells predominated at 6 months. CONCLUSION:
      These results suggest that the presence of cytotoxic activity in the peripheral
      blood of the patient was due to both cytotoxic T cells and NK cells. The
      cytotoxic activity was lowest prior to surgery and increased postoperatively.

PMID- 9624554
TI  - Utility of immunohistochemical detection of high molecular weight cytokeratin for
      differential diagnosis of proliferative conditions of the prostate.
AB  - BACKGROUND: Differential diagnosis of adenocarcinoma from other proliferative
      conditions in the prostate is often problematic. Immunohistochemistry using an
      antibody (34 beta E12) to high molecular weight cytokeratin, specifically present
      in basal cells of the prostate, could clearly demonstrate the presence or absence
      of these cells in the proliferating glands and thus provide an important clue in
      cancer diagnosis. METHODS: To examine the utility of immunostaining using 34 beta
      E12, we examined 88 equivocal lesions. Twenty lesions with apparently benign and
      malignant features were added as controls. We compared the morphologic features
      of these lesions with their immunoreactivities toward 34 beta E12 on a personal
      computer display following storage on the MICROPHOT-FXA system. RESULTS:
      Proliferating glands in all 20 benign lesions had 34 beta E12-reactive basal
      cells, but none of the malignant lesions did. The equivocal lesions were
      categorized on morphologic grounds into 2 groups: possibly benign and possibly
      malignant. Forty-five (51.1%) of the 88 equivocal lesions, were positive for 34
      beta E12. These included 35 of the 45 (77.8%) possibly benign lesions and 10 of
      the 43 (23.3%) possibly malignant lesions. Among the equivocal lesions, 10
      considered possibly benign on morphologic grounds showed negative reactivities,
      and 10 considered possibly malignant showed positive reactivities. Even through
      comparison on the computer display, no difference in morphology could be
      discovered between the negative and positive lesions in either group. CONCLUSION:
      Immunohistochemical procedures using 34 beta E12 are indispensable in the
      diagnosis of equivocal prostate lesions.

PMID- 9624555
TI  - Diffusion of piperacillin, cefotiam, minocycline, amikacin and ofloxacin into the
      prostate.
AB  - BACKGROUND: The successful treatment of bacterial prostatitis depends on an
      effective antimicrobial concentration in prostatic tissue against the infecting
      organism. In this study we compared the diffusion of 5 types of antimicrobials
      into the prostate. METHODS: The concentrations of piperacillin, cefotiam,
      minocycline, amikacin, and ofloxacin were determined in prostatic fluid,
      prostatic tissue, and serum 2.5 to 3 hours after a single administration from 55
      patients with benign prostatic hypertrophy. RESULTS: Although amikacin showed the
      highest mean concentration both in prostatic tissue and prostatic fluid, the
      prostatic tissue/serum ratio was significantly higher (P < 0.01) for ofloxacin
      (1.49 +/- 0.80) and minocycline (0.94 +/- 0.39) compared with those for amikacin
      (0.49 +/- 0.21) and piperacillin (0.21 +/- 0.15). Also, the prostatic fluid/serum
      ratio was lower than the prostatic tissue/serum ratio for each drug, however, the
      prostatic fluid/serum ratio of ofloxacin was significantly higher than that of
      other antimicrobials tested (P < 0.01). CONCLUSION: These results support earlier
      studies demonstrating that fluoroquinolones are a useful class of antimicrobials
      for the treatment of chronic bacterial prostatitis. They also suggest that in
      view of the pharmacokinetic properties and antimicrobial activities, amikacin and
      minocycline may be alternate antimicrobial options for selected patients with
      bacterial infections of the prostate.

PMID- 9624556
TI  - Long-term follow-up study of penile cancer.
AB  - BACKGROUND: We reviewed the outcomes for patients with penile cancer to determine
      factors predictive of their survival. METHODS: Between 1966 and 1996, 59 patients
      with penile cancer were treated at Kobe University Hospital. The median follow-up
      period was 109 months (range, 4 to 240 months). The prognostic factors were
      determined by multivariate analysis. Disease progression rates, according to
      stage and the type of surgery, were studied. RESULTS: The 5- and 10-year, cause
      specific survival rates were 75.9% and 73.8%, respectively. Lymph node
      involvement, tumor stage, and tumor differentiation were the independent risk
      factors identified by multivariate analysis. Among the patients at stage 1 and 2,
      none of the 29 patients treated with early lymphadenectomy showed recurrence in
      the inguinal region, while 4 (27%) of 15 patients without lymphadenectomy showed
      such recurrence. CONCLUSION: Our results suggest that tumor stage, lymph node
      involvement, and tumor differentiation are significant prognostic factors for
      survival, and that early inguinal lymphadenectomy would improve the prognosis of
      patients with stage 1 or 2 penile cancer.

PMID- 9624557
TI  - Comparative study between corpus cavernosum-electromyography findings and
      electron microscopy of cavernosal muscle biopsies in erectile dysfunction
      patients.
AB  - BACKGROUND: Biopsy and electrical activity recordings of the corpus cavernosum
      are 2 new diagnostic methods for the evaluation of impotent men. We evaluated the
      corpus cavernosum ultrastructure and electromyography (EMG) recordings from
      patients with erectile dysfunction. METHODS: Twenty erectile dysfunction patients
      with veno-occlusive dysfunction underwent a detailed history, physical
      examination, biochemical tests, hormonal analysis, injection of an intracavernous
      vasoactive agent (60 mg papaverine-HCl), color penile Doppler ultrasonography,
      cavernosometry/ cavernosography and corpus cavernosum electromyography (CC-EMG).
      Thirteen patients underwent total vein ligation and 7 had penile prosthesis
      implantations. Tissue samples were obtained during surgery from both corpora
      cavernosa and examined by transmission electron microscopy. Control corporal
      tissue samples were taken from 3 cadavers. RESULTS: In 15 patients, CC-EMG
      recordings were 15.6 +/- 0.65 microV in the flaccid state, which decreased in 13
      patients after papaverine (5.61 +/- 0.25 microV; P < 0.001). Five patients with
      diabetes mellitus had low amplitudes in the flaccid state (5.26 +/- 0.45 microV),
      which did not vary significantly after a papaverine injection (4.99 +/- 0.75
      microV). The pathology of the corpus cavernosum biopsy specimens revealed a
      smooth muscle cell thickened basal membrane, dilated rough endoplasmic reticulum,
      and increased numbers of fibroblasts, but ultrastructurally normal endothelial
      cells lining the sinusoids. There was no difference between samples from diabetic
      or nondiabetic patients, or from either side of the corpora cavernosa. The only
      pathologic change observed in the controls was mitochondrial swelling.
      CONCLUSION: CC-EMG is less invasive and a valuable method in patients with
      erectile dysfunction, whereas no specific findings were observed from penile
      biopsy specimens.

PMID- 9624558
TI  - Renal tubular apoptosis after release of ureteral obstruction in the rat kidney.
AB  - BACKGROUND: Information concerning the mechanisms underlying recovery from
      hydronephrosis is limited. The frequency of apoptosis during healing from
      hydronephrosis was studied using a rat kidney model. METHODS: The presence of
      apoptosis was studied using an in situ DNA 3' end labeling method, electron
      microscopy, and agarose gel electrophoresis. RESULTS: The degree of apoptosis in
      both the medulla and cortex gradually increased during ureteral obstruction as
      shown by in situ DNA 3' end labeling. Release of the ureteral obstruction
      resulted in a further increase in the degree of apoptosis in the medulla and
      cortex. The increase in apoptosis in the medulla was transient and lasted for
      only 4 days following release, while that in the cortex continued for at least 3
      weeks. Apoptosis in the glomerulus was not observed. Electron microscopy revealed
      cells with aggregated chromatin in compact granular masses that abutted the
      nuclear membrane. Following release of ureteral obstruction, DNA fragmentation
      characteristic of apoptosis was visible on agarose gel electrophoresis.
      CONCLUSION: These results suggest that apoptosis is involved in post-obstructive
      tubular damage in the rat kidney.

PMID- 9624559
TI  - Apoptosis and carcinogenesis: morphologic observations in the rat bladder treated
      with N-butyl-N-(4-hydroxybutyl)nitrosamine.
AB  - BACKGROUND: We investigated the role of apoptosis in rat bladder carcinogenesis
      induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). METHODS: Apoptosis was
      detected in BBN-induced rat bladder lesions by routine hematoxylin and eosin
      (H&E) staining, terminal deoxynucleotidyl transferase-mediated deoxyuridine
      triphosphate-biotin nick end labeling (TUNEL), and transmission electron
      microscopic examinations. RESULTS: After administration of BBN, various
      pathologic changes were observed in the rat bladder after intervals of between 4
      and 28 weeks. Through a comparative study in serial sections, the incidence of
      apoptosis, detected by either routine H&E staining or TUNEL staining, displayed
      marked elevation in BBN-induced rat bladder lesions, as compared to that in the
      normal epithelium of the rat bladder, particularly in invasive transitional cell
      carcinoma. Apoptotic cells with different morphologic features were
      ultrastructurally demonstrated in a series of rat bladder lesions. Significant
      group differences in the incidence of apoptosis were seen among the BBN-induced
      lesions and the normal epithelium of the rat bladder, and among the invasive
      transitional cell carcinomas and other lesions, before the tumor cells were seen
      to invade the rat bladder. CONCLUSION: Our data suggest that apoptosis may be
      closely related to carcinogenesis and tumor invasion of the rat bladder induced
      by BBN, and that the comparative study of serial sections, each stained by H&E
      and TUNEL, combined with electron microscopic observation, may provide the most
      reliable informations in semiquantitative assessment of apoptosis.

PMID- 9624561
TI  - Regulation of invasive potential of human prostate cancer cell lines by
      hepatocyte growth factor.
AB  - BACKGROUND: The growth and progression of prostate cancer depends on the stromal
      epithelial interaction which is under paracrine control. Hepatocyte growth factor
      (HGF), produced by mesenchymal cells, is a multifunctional growth factor
      stimulating the movement and growth of epithelial cells including cancer cells.
      We therefore assessed the relationship between the invasive potential of prostate
      cancer and HGF in vitro. METHODS: Three human prostate cancer cell lines were
      used including PC-3 and DU145 (androgen-independent), and LNCaP (androgen
      dependent). We studied the expression of the HGF receptor c-met proto-oncogene (c
      met) by Western blot analysis, and also determined the effects of HGF on cell
      scattering, and the mechanisms of invasion and proliferation, by microscopic
      observation, the matrigel invasion chamber assay, and the MTT assay. RESULTS: c
      met was detected in PC-3 and DU145 cells, but not in the LNCaP cells. There was
      increased cell motility in the scatter assay and an increased cell invasive
      potential in the matrigel invasion chamber assay by stimulation with HGF only
      with DU145 cells. CONCLUSION: HGF plays an important role in the invasion and
      metastasis of the DU145 cell line through a paracrine mechanism mediated by the c
      metreceptor. In the PC-3 cell line, the lack of downstream signal transduction
      after the c-met receptor is suggested.

PMID- 9624560
TI  - Pharmacologic actions of temiverine (p-INN) and its active metabolite, RCC-36, on
      isolated human urinary bladder muscle.
AB  - BACKGROUND: Temiverine (p-INN) is a newly synthesized drug that is expected to
      have anticholinergic action. We investigated the pharmacologic actions of
      temiverine and its active metabolite, RCC-36, on isolated human bladder. METHODS:
      Effects of temiverine and RCC-36 on the detrusor contractions induced by
      acetylcholine, potassium chloride (KCl), calcium chloride (CaCl2), and electric
      field stimulation were evaluated using the muscle-bath technique, and compared
      with the effects of atropine and oxybutynin. RESULTS: Atropine (10(-9) to 10(-6)
      mol/L), oxybutynin (10(-8) to 10(-5) mol/L), temiverine (10(-8) to 10(-5) mol/L),
      and RCC-36 (10(-8) to 3 x 10(-6) mol/L) caused a parallel shift to the right of
      the concentration-response curves to acetylcholine stimulation. The rank order of
      pA2 value was atropine > oxybutynin = RCC-36 > temiverine. Atropine did not
      suppress the maximum contractile response to acetylcholine, but the other drugs
      significantly suppressed this at the higher concentrations. Each drug caused a
      concentration-dependent inhibition of KCl (80 mmol/L)-, and CaCl2 (5 mmol/L)
      induced contractile responses. Rank order of maximum inhibition was RCC-36 =
      temiverine > oxybutynin > atropine. Each drug caused a concentration-dependent
      inhibition of electric field-induced contraction with or without 10(-6) mol/L
      atropine pretreatment. Maximum inhibitions of temiverine and RCC-36 were
      significantly greater than that of oxybutynin. CONCLUSION: Atropine, oxybutynin,
      temiverine, and RCC-36 have different efficacies and potencies of anticholinergic
      and calcium antagonistic activity on isolated human detrusor muscles.
      Furthermore, temiverine and RCC-36 have significant inhibitory actions toward the
      atropine-resistant part of contractions, which may be related to the calcium
      antagonistic actions of these compounds.

PMID- 9624562
TI  - Establishment and characterization of a new human testicular seminoma cell line,
      JKT-1.
AB  - BACKGROUND: A new human testicular cancer cell line (JKT-1) was established,
      successfully transplanted into nude mice, and has been maintained for over 2
      years. We examined the biological characteristics of JKT-1 cells. METHODS: The
      original material for JKT-1 was derived from a primary lesion of a left
      testicular seminoma (pure, typical-type) from a 40-year-old male. The tumor
      tissue was minced and cultured according to the explant culture method. The cells
      grew as a monolayer with a doubling time of 28.5 hours. RESULTS: JKT-1 produced
      neither alpha-fetoprotein or beta-human chorionic gonadotropin, but showed strong
      immunoreactivities for vimentin and placental alkaline phosphatase. A chromosomal
      analysis revealed a modal number of 66 with loss of the Y chromosome.
      Morphologically, JKT-1 cells have a pleomorphic polygonal shape, an increase in
      the nuclear/cytoplasm ratio, and poor development of organelle and desmosome-like
      cell-cell junctions. JKT-1 cells were subcutaneously transplanted into the backs
      of 6-week-old nude mice, and grew classical seminomatous tissue. CONCLUSION: This
      report profiled a seminoma cell line established for both in vitro and in vivo
      experimental systems. Future studies are planned to investigate germ cells using
      this seminoma line.

PMID- 9624563
TI  - Renal cell carcinoma with gallbladder metastasis.
AB  - The nature of polypoid masses within the gallbladder is difficult to define
      preoperatively. Tumors larger than 1 cm in size are strongly related to
      malignancy, but they are not always primary tumors of the gallbladder. We present
      a patient who underwent radical surgery for renal cell carcinoma and the
      preoperative finding of a polypoid mass within the gallbladder turned out to be a
      metastatic lesion.

PMID- 9624564
TI  - Carcinoembryonic antigen positive adenocarcinoma of a female urethral
      diverticulum: case report and review of the literature.
AB  - Paraurethral glands of the female urethra, which are assumed to be
      embryologically homologous to the male prostate gland, are possible origins for
      diverticular cancer of the urethra. A case of primary adenocarcinoma arising in a
      female urethral diverticulum is presented. Pathology revealed a columnar/mucinous
      type adenocarcinoma which stained positively for carcinoembryonic antigen (CEA)
      and negatively for PSA. Normal paraurethral ducts located near the urethra and
      normal urethral epithelium also stained positively for CEA. These findings
      suggest that the adenocarcinoma in our case originated from the paraurethral duct
      near the urethral lumen.

PMID- 9624565
TI  - Transitional cell carcinoma in the fossa navicularis of the male urethra: a case
      report.
AB  - We report a case of transitional cell carcinoma arising in the fossa navicularis
      of the male urethra. The patient was 87-years-old and noticed intermittent
      urethral bleeding. We could see a tumor protruding from the urethral meatus,
      removed it successfully, and irradiated the base of the tumor with Nd:YAG laser.
      The histologic finding was grade 2 transitional cell carcinoma, pTa. There was no
      other tumor in the urinary bladder or upper urinary tract. The postoperative
      course was uneventful and the patient showed no evidence of disease for 4 months
      after treatment but died from other causes.

PMID- 9624566
TI  - Transitional cell papilloma in the fossa navicularis is positive for human
      papillomavirus.
AB  - Transitional cell papillomas rarely develop in the fossa navicularis of the
      anterior urethra. We observed such a case of transitional cell papilloma and
      detected human papillomavirus type 6 (HPV-6) DNA in this papilloma by polymerase
      chain reaction. To our knowledge this report is the first of HPV-infected
      transitional papilloma in the anterior urethra.

PMID- 9624567
TI  - Congenitally isolated cavernous bodies.

PMID- 9624568
TI  - Testicular microlithiasis with mediastinal choriocarcinoma: a case report.
AB  - A 19-year-old Japanese male developed a cough, chest pain, and high fever. CT of
      the chest revealed a bulky mediastinal tumor (13 x 10 x 8 cm) and bilateral
      multiple pulmonary nodules. CT of the abdomen and pelvis was normal. Laboratory
      evaluation showed a beta human chorionic gonadotropin (beta HCG) level of 985
      ng/mL. Testicular ultrasonography demonstrated multiple, bilateral punctate
      echoes characteristic of testicular microlithiasis (TM). No primary testicular
      tumor was detected. Needle biopsies of the testes did not reveal cancer and
      calcification. Transthoracic needle biopsy of the mediastinal tumor showed
      choriocarcinoma. No correlation is known between TM and choriocarcinoma without
      testicular cancer, but the incidence of TM in this patient may reflect his high
      human chorionic gonadotropin level.

PMID- 9624569
TI  - Capillary isoelectric focusing and isoelectric buffers: an evolving scenario.
AB  - The present review offers a new look at capillary isoelectric focusing (cIEF) by
      centering on the most troublesome aspects of the technique, namely: 1) how to
      modulate the slope of the pH gradient, for increasing resolution (equivalent to
      pH gradient engineering, as easily available in immobilized pH gradients); and 2)
      how to keep proteins in solution at (and in the proximity of) the pl value. A
      simple solution is offered in the first case: addition, to the standard 2-pH
      units interval, of separators or spacers, i.e., of amphoteric molecules (either
      single or in combination) able to locally flatten the pH and increment
      resolution. Examples of the separation of fetal and glycated hemoglobins are
      provided. In the second case, a unique solubilization power (while maintaining
      full protein integrity and enzyme activity) is obtained if class I solubilizers
      are used. They consist of mixtures of sugars (e.g., sucrose and sorbitol) at ca.
      1 M concentration, with zwitterions (up to 1 M) such as the class of nondetergent
      sulfobetaines, but also taurine and some of the Good's buffers (e.g., CAPS). In
      these solvents, the protein exists in a state of superhydration and its
      solubility is greatly augmented. The review ends with an excursus on the use of
      isoelectric buffers in zone electrophoretic separations. Such isoelectric buffers
      offer unique advantages: They permit very-high-voltage gradients (up to 1000
      V/cm) and thus minimize analysis times (down to a few min in 30-35 cm long
      capillaries). This results in a marked increase in resolution, due to minimal
      diffusion-driven peak spreading. Such buffers are finding unique applications for
      generating peptide maps of tryptic digests of proteins and also in the analysis
      of oligonucleotides.

PMID- 9624570
TI  - Rapid SDS gel capillary electrophoretic analysis of proteins.
AB  - Capillary sodium dodecyl sulfate (SDS) electrophoresis is a powerful and
      sensitive method for the qualitative and quantitative microanalysis of molecular
      mass for biopolymers. Usually, a separation is carried out in the long part of
      the capillary (20-50 cm), before the detection window, with separation times of
      15-50 min. The separation of model proteins and real fractions of cell culture
      broth in the short part (7 cm) of the capillary, behind the window, was
      investigated. The analysis time could be reduced to less than 5 min. A comparison
      with established separation techniques is presented. Different modes of injection
      (by pressure and electrokinetic) were considered. The proposed method can be used
      for on-line monitoring of biotechnological processes.

PMID- 9624571
TI  - Profiling clinically important metabolites in human urine by capillary
      electrophoresis and electrochemical detection.
AB  - Clinically important metabolic markers, including alditols, carbohydrates, and
      amino acids, were profiled directly in urine by capillary electrophoresis with
      electrochemical (EC) detection via oxidation at a copper electrode. CE in
      strongly basic buffers was found to provide an effective means with which to
      achieve the separation of these compounds with the buffer pH being the most
      important factor governing the separation. EC detection at a copper electrode
      provided a convenient means for detecting all of these species with sensitivity
      usually down to the femtomole level. Most important, both the CE separation and
      EC detection were performed directly on the urine samples without extensive
      sample cleanup and with no analyte derivatization required. Specific compounds
      that were able to be identified and quantitated included glucose, galactose,
      creatinine, and uric acid. All were found to be present at normal levels in urine
      samples from healthy subjects.

PMID- 9624572
TI  - Capillary electrophoresis for regulatory analysis: is it ready? Problems
      encountered during an interlaboratory study utilizing capillary electrophoresis.
AB  - Recently, the Northeast Regional Laboratory of the Food and Drug Administration
      conducted a collaborative study on the method to determine histamine in tuna by
      capillary electrophoresis. This study, under the guidance of the AOAC
      International, was the first of its kind involving the use of CE and was
      undertaken to establish official monograph status. The results of the
      collaborative study, however, were highly variable. Percent recovery data
      obtained by 11 collaborators ranged from 54 to 281%, with an average of 111%. In
      this paper, problems with reproducibility, and factors such as low sensitivity,
      noisy baselines, and variable migration times encountered by collaborators using
      various commercial capillary electrophoresis units are discussed.

PMID- 9624573
TI  - Quantitation of RT-PCR products of bFGF-mRNA by capillary electrophoresis and
      laser-induced fluorescence.
AB  - The numerous challenges of modern biology and medical science require the
      development of analytical methodologies of extreme sensitivity and resolving
      power. Because it deals with the extraordinary complexity of biological mixtures
      and minute samples, capillary electrophoresis combined with laser-induced
      fluorescence (LIF) is now one of the most popular analytical biotechniques. Using
      polymer matrices and very high voltages, it allows the separation of very low
      quantities of microsamples and the selective detection of fluorescent species at
      a level of a few thousand molecules. This method of analysis has been used to
      quantitate reverse transcription-polymerase chain reaction (RT-PCR) products. In
      the authors' laboratory, they were looking for a means of analyzing mRNAs of
      cytokines. In the first attempt, they chose to quantitate RT-PCR products of
      basic fibroblast growth factor (bFGF)-mRNA, which could be involved in
      atherosclerosis. The results on two patients confirm the lower quantity of bFGF
      expressed in internal mammary athery (IMA) biopsies compared to human aortic
      cells. This study shows the usefulness of CE-LIF to identify and quantitate RT
      PCR products and its ability to be used in clinical studies, to find very low
      levels of bFGF expression in atheroma biopsies.

PMID- 9624574
TI  - High-throughput DNA sequencing on a capillary array electrophoresis system.
AB  - A capillary array electrophoresis apparatus capable of running and analyzing 48
      DNA sequencing samples simultaneously has been constructed. The instrument uses a
      replaceable sieving buffer and incorporates a convenient method for introducing
      the buffer into the capillaries. Data from laser-induced fluorescence are
      collected as four separate images, one for each optical channel. The integrated
      data analysis software employs an open architecture that allows use of any DNA
      base-calling algorithm. DNA sequencing runs are completed in approx. 1 hr
      (approximately 500 bases), and instrument turnaround time between runs is less
      than 15 min. Overall, the instrument throughput is on the order of 720
      templates/day, or 360,000 bases/day.

PMID- 9624575
TI  - Sensitive determination of arsenite by capillary zone electrophoresis with direct
      photometric detection.
AB  - The effect of the sample matrix type (water and aqueous solutions containing
      phosphate buffer, 3-[cyclohexylamino]-1-propanesulfonic acid [CAPS], and sodium
      chloride solutions) on the migration behavior and peak parameters of As(III),
      As(V), and dimethylarsinate was studied. CAPS is found to be the most effective
      additive for As(III) peak amplification. The reasons for additive influence are
      discussed. The pH of the carrier electrolyte has been optimized with respect to
      As(III) peak height and shift of the peak position in electropherograms from the
      position of the sample matrix plug. Under optimal conditions, a peak efficiency
      expressed as the number of theoretical plates per meter (N) of 50,460 and a
      detection limit of 0.05 mg L-1 for As(III) were achieved.

PMID- 9624577
TI  - Cells and molecules involved in the development of sarcoid granuloma.
AB  - Although the etiology of sarcoidosis is still unknown, characteristic morphologic
      aspects and immunohistological patterns of sarcoid granulomatous lesions suggest
      that they are the consequence of an exaggerated immunological response against an
      undefined antigen which persists at different sites of disease involvement. This
      article reviews the newly emerging hypothesis regarding the molecular bases which
      drive the development of sarcoid granulomas. The accumulation of Th1 cells
      represents the pivotal step along the series of events that lead to the formation
      of granuloma; furthermore, a set of biological mediators of the immune response
      define immune regulatory networks that may contribute to tissue damage. It is
      also thought that shifts of the Th1/Th2 networks and alterations in the complex
      networks between immunocompetent cells and mesenchymal cells may set the stage
      for the remodeling of tissues surrounding granulomatous lesions.

PMID- 9624576
TI  - Regulation and function of mast cell proteases in inflammation.

PMID- 9624579
TI  - IgE antibodies in sera from patients with bullous pemphigoid are autoantibodies
      preferentially directed against the 230-kDa epidermal antigen (BP230)
AB  - Bullous pemphigoid (BP) is unique among autoimmune skin diseases in which a high
      serum IgE level has been detected. We sought to determine the antigenic
      specificity of these IgE antibodies in 39 BP sera by immunofluorescence
      microscopy, immunoblot, and ELISA. The patient's sera contained IgG antibodies to
      230-kDa (BP230) (n = 20), 180-kDa (BP180) (n = 9), and both BP230 and BP180 (n =
      10) antigens. Serum IgE levels varied from 29 to 5000 kIU/L (mean +/- SD, 856 +/-
      1426 kIU/L), among which sera containing IgG antibodies to BP230 had an IgE level
      on average 4.3 times higher than anti-BP180 sera. IgE antibodies in 18 sera were
      found to be autoantibodies reactive either with an epidermal component of
      basement membrane zone by immunofluorescence microscopy on 1 M NaCl-split skin or
      with a 230-kDa antigen by immunoblots of cultured human keratinocytes. The 230
      kDa epidermal antigen recognized by IgE antibodies comigrated with the BP230 as
      labeled by a specific human monoclonal antibody. IgE anti-BP230 antibodies in
      patients' sera were always associated with IgG autoantibodies. No sera contained
      IgE antibodies to BP180 or to any other epidermal or dermal antigens as verified
      by immunoblot and ELISA. A good correlation was found between the presence of IgE
      circulating autoantibodies and the level of serum IgE (P < 0.004). IgE antibodies
      to BP230, like IgG autoantibodies, were mapped primarily to the C-terminal end of
      the protein, as they labeled rBP55, a BP230 recombinant protein encoded by a cDNA
      for the C-terminal end of BP230.

PMID- 9624578
TI  - Immunization with Haemophilus influenzae type b conjugate vaccine in children
      given bone marrow transplantation: comparison with healthy age-matched controls.
AB  - Forty-seven patients (age range, 7 months-18 years) with malignant (38 cases) and
      nonmalignant (9 cases) disorders given an allogeneic or an autologous bone marrow
      transplantation (BMT) were immunized with Haemophilus influenzae type b (Hib)
      polysaccharide-diphtheria toxoid conjugate vaccine administered in a single dose
      at different time points after transplantation. Results were compared with those
      of 13 healthy children matched for age and sex who received the same immunization
      schedule. Serum and saliva samples for measurement of total IgG subclass and
      specific antibody levels were obtained from patients and healthy controls before
      and 3 weeks after vaccination. Twenty-five of the 47 patients (53%) had a
      specific anti-Hib IgG response, while an effective IgA and IgM response was
      mounted by 23 (49%) and 11 (23%) children, respectively. In the control group, 13
      of 13 subjects mounted a specific IgG antibody production (P < 0.005 in
      comparison to the patients' response rate), while an IgA and IgM response was
      demonstrated in 12 (92%; P < 0.01 compared to transplanted patients) and 7 (54%;
      P < 0.05 in comparison to BMT recipients) children, respectively. Lapse of time
      from BMT to immunization was the most important factor predicting antibody
      response, as proved by an effective increase in prevaccination specific IgG
      levels in the majority of patients vaccinated after 2 years from transplant. Our
      data demonstrate that BMT recipients have a reduced capacity to mount an antibody
      response to polysaccharide antigens compared to normal controls, even when a
      protein-conjugated vaccine is employed. Since time after transplant is the major
      factor influencing the recovery of immune reactivity to polysaccharide antigens,
      the ontogeny of the B cell repertoire seems to follow a predetermined sequential
      program of development.

PMID- 9624581
TI  - Molecular cloning and functional characterization of human MIP-1 delta, a new C-C
      chemokine related to mouse CCF-18 and C10.
AB  - We have isolated a novel human C-C chemokine, MIP-1 delta from a human fetal
      spleen cDNA library. The human MIP-1 delta cDNA has an unusually long 400-bp 5
      prime untranslated region and a predicted 113-amino acid protein of 10 kDa. The
      coding sequence contains a signal peptide of 21 amino acids, indicating that the
      mature protein has 92 amino acids (8 kDa). Recombinant human MIP-1 delta produced
      by transfected human embryonic kidney 293 cells produced an 8-kDa protein, which
      confirmed the presence of a signal peptide. Compared with other human C-C
      chemokines, human MIP-1 delta shows the highest homology with human HCC-1, CK
      beta-8, murine C10, and CCF18 (MIP-1 gamma). The human MIP-1 delta gene is
      localized on chromosome 17 where most of the C-C chemokine superfamily is
      located. Human MIP-1 delta is expressed in T and B lymphocytes, NK cells,
      monocytes, and monocyte-derived dendritic cells, but not in bone marrow-derived
      dendritic cells. Its expression can be induced by other proinflammatory cytokines
      in monocytes and dendritic cells. Human MIP-1 delta is chemotactic for T cells
      and monocytes, but not for neutrophils, eosinophils, or B cells. Human MIP-1
      delta induced calcium flux in human CCR1-transfected cells.

PMID- 9624580
TI  - Effect of lidocaine on neutrophil chemotaxis in newborn infants.
AB  - Anesthetic drugs can influence the immune system, particularly granulocyte
      function. The goal of the present study was to evaluate if lidocaine used for
      epidural anesthesia during cesarean section can influence neonatal neutrophil
      chemotaxis. We measured chemotaxis and plasma cord lidocaine and cortisol levels
      in (A) 15 infants born by cesarean section with epidural anesthesia, (B) 15
      infants born by vaginal delivery, and (C) 20 infants born by cesarean section
      with general anesthesia. Chemotaxis levels were significantly lower in group A
      infants (35.5 +/- 16.1 microns) compared to groups B (54.6 +/- 10.5 microns) and
      C (71.4 +/- 23 microns). The highest cortisol levels were observed in vaginally
      delivered infants. A significant inverse relationship was observed between
      chemotaxis and lidocaine levels (r = -0.6, P = 0.016) in infants born by cesarean
      section after epidural anesthesia, while no significant correlation was observed
      between chemotaxis and cortisol level. In conclusion, lidocaine, transferred
      through the placenta to the fetus during epidural anesthesia, may have an
      inhibitory effect on chemotaxis.

PMID- 9624582
TI  - Interleukin-1 alpha increases the preferential cytotoxicity of an interleukin-2
      diphtheria toxin fusion protein against neoplastic lymphocytes from patients with
      the Sezary syndrome compared to normal lymphocytes.
AB  - DAB389IL-2 is a recombinant fusion toxin composed of the diphtheria A chain and a
      protion of the translocating region of the diphtheria B chain, replacing the
      receptor binding domain with human IL-2. DAB389IL-2 can be safely administered to
      humans with mycosis fungoides (MF) or Sezary syndrome (SS), and antineoplastic
      effects occur. This agent binds optimally to the high-affinity IL-2R. The
      decreased efficiency of uptake by neoplastic cells which do not express the high
      affinity IL-2R represents a potential limitation. Treatment of the HUT-78
      cutaneous T-cell lymphoma with IL-1 alpha preceding exposure to DAB389IL-2
      overcame their resistance to the toxin, IL-1 alpha inducing high-affinity IL-2R
      expression. Similarly, pretreatment with IL-1 alpha of SS patient lymphocytes
      demonstrated increased cytotoxicity compared to treatment with the fusion toxin
      alone. Normal lymphocytes and monocytes were not sensitive to DAB389IL-2 when
      pretreated with IL-1 alpha, suggesting a differential sensitivity which may be
      exploited clinically in the treatment of lymphomas.

PMID- 9624583
TI  - Association of phenotypic changes in B cell lymphocytes and plasma viral load in
      human immunodeficiency virus-infected patients.
AB  - Many B cell abnormalities have been reported in human immunodeficiency virus
      (HIV)-infected patients, including changes in the expression of mu, gamma, and
      CD22 molecules on the cell surface. Phenotypic changes in these markers on B
      cells isolated from HIV-seropositive patients with high or low levels of plasma
      viremia were measured. The phenotypic changes in B cells isolated from such
      patients were compared with the markers on B cells isolated from HIV-seronegative
      individuals using three-color flow cytometry. HIV patients showed a reduction in
      the proportion of mature B cells isolated from peripheral blood mononuclear cells
      compared with B cells isolated from HIV-seronegative individuals. An increase in
      the proportion of B cells expressing both mu and gamma molecules on the cell
      surface was also seen in association with high-HIV plasma viremia. A low plasma
      viral load was accompanied by a reduction in the proportion of B cells expressing
      both mu and gamma molecules to a level comparable to those seen in HIV
      seronegative individuals. HIV-seropositive individuals demonstrated an increase
      in the proportion of committed B cells, as indicated by an increase in the
      proportion of B cells expressing gamma molecules. This observation may explain
      the poor humoral response of HIV seropositive patients to neo-antigens. Our
      results demonstrate that phenotypic changes indicative of in vivo B cell
      activation and an increase in immature cells are associated with HIV infection,
      particularly with a high plasma viral load. Phenotypic changes in B cell markers
      may correlate with functional deficits of B cells.

PMID- 9624584
TI  - Immunocytochemical localization of enkephalins in the brain of the African
      lungfish, Protopterus annectens, provides evidence for differential distribution
      of Met-enkephalin and Leu-enkephalin.
AB  - The distribution of various opioid peptides derived from proenkephalin A and B
      was studied in the brain of the African lungfish Protopterus annectens by using a
      series of antibodies directed against mammalian opioid peptides. The results show
      that both Metenkephalin- and Leu-enkephalin-immunoreactive peptides are present
      in the lungfish brain. In contrast, enkephalin forms similar to Met-enkephalin
      Arg-Phe, or Met-enkephalin-Arg-Gly-Leu, as well as mammalian alpha-neoendrophin,
      dynorphin A (1-8), dynorphin A (1-13), or dynorphin A (1-17) were not detected.
      In all major subdivisions of the brain, the overwhelming majority of Met
      enkephalin- and Leu-enkephalin-immunoreactive cells were distinct. In particular,
      cell bodies reacting only with Leu-enkephalin antibodies were detected in the
      medial subpallium of the telencephalon, the griseum centrale, the reticular
      formation, the nucleus of the solitary tract, and the visceral sensory area of
      the rhombencephalon. Cell bodies reacting only with Met-enkephalin antibodies
      were found in the lateral subpallium of the telencephalon, the caudal
      hypothalamus, and the tegmentum of the mesencephalon. The preoptic
      periventricular nucleus of the hypothalamus exhibited a high density of
      Metenkephalin-immunoreactive neurons and only a few Leu-enkephalin-immunoreactive
      neurons. The distribution of Met-enkephalin- and Leu-enkephalin-immunoreactive
      cell bodies and fibers in the lungfish brain showed similarities to the
      distribution of proenkephalin A-derived peptides described previously in the
      brain of land vertebrates. The presence of Met-enkephalin- and Leu-enkephalin
      like peptides in distinct regions, together with the absence of dynorphin-related
      peptides, suggests that, in the lungfish, Met-enkephalin and Leu-enkephalin may
      originate from distinct precursors.

PMID- 9624585
TI  - Interconnections among nuclei of the subcortical visual shell: the
      intergeniculate leaflet is a major constituent of the hamster subcortical visual
      system.
AB  - The intergeniculate leaflet (IGL), a major constituent of the circadian visual
      system, is one of 12 retinorecipient nuclei forming a "subcortical visual shell"
      overlying the diencephalic-mesencephalic border. The present investigation
      evaluated IGL connections with nuclei of the subcortical visual shell and
      determined the extent of interconnectivity between these nuclei. Male hamsters
      received stereotaxic, iontophoretic injections of the retrograde tracer, cholera
      toxin beta fragment, or the anterograde tracer, Phaseolus vulgaris-leucoagglutin,
      into nuclei of the pretectum (medial, commissural, posterior, olivary, anterior,
      nucleus of the optic tract, posterior limitans), into the superior colliculus, or
      into the visual thalamic nuclei (lateral posterior, dorsal lateral geniculate,
      intergeniculate leaflet, ventral lateral geniculate). Retrogradely labeled cell
      bodies identified nuclei with afferents projecting to the site of injection,
      whereas the presence of anterogradely labeled fibers with terminals revealed
      brain nuclei targeted by neurons at the site of injection. The IGL projects
      bilaterally to all nuclei of the visual shell except the lateral posterior and
      dorsal lateral geniculate nuclei. The IGL also has afferents from the same set of
      nuclei, except the nucleus of the optic tract. The extensive bilateral efferent
      projections distinguish IGL from the ventral lateral geniculate nucleus. The
      superior colliculus, commissural pretectal, olivary pretectal, and posterior
      pretectal nuclei also project bilaterally to the majority of subcortical visual
      nuclei. The IGL has a well-established role in circadian rhythm regulation, but
      there is as yet no known function for it in the larger context of the subcortical
      visual system, much of which is involved in oculomotor control.

PMID- 9624586
TI  - Distribution of connexin43 immunoreactivity in the retinas of different
      vertebrates.
AB  - The distribution of Connexin43 (Cx43) was examined by immunoblotting and
      immunofluorescence microscopy in the retinas of five different vertebrates by
      using a C-terminal specific peptide antibody. The specificity of the antibody was
      proved on immunoblots, in which it showed cross reactivity with a 43-kDa protein
      in rat heart homogenates as well as in homogenates of rabbit, rat, chicken,
      turtle, and fish (carp and zebrafish) retinas. Immunofluorescence histochemistry
      with retinal cryosections revealed the presence of Cx43 in the retinal pigment
      epithelium cells of all tested species and in blood vessels of vascularized
      retinas (fish and rat). Cx43 immunoreactivity was further localized in the stria
      medullaris of rabbit retina, in the nerve fiber layer of rat retina, most likely
      in astrocytes, and in the area of the outer limiting membrane of the fish retina,
      most likely representing Cx43 in Muller glia cells. A punctate Cx43
      immunoreactive pattern consistent with gap junctions was also detected in the
      outer plexiform layer of carp and zebrafish retinas, and a specific amacrine cell
      type, which ramified in two layers of the inner plexiform layer, was labeled in
      the zebrafish retina. The present results are in accordance with previous
      findings showing the abundance of Cx43 in astrocytes, endothelium, and epithelial
      cells. However, the presence of Cx43 immunoreactivity in a specific population of
      amacrine cells of the zebrafish retina might indicate that a Cx43-like protein is
      also expressed in neurons.

PMID- 9624587
TI  - Anatomical regeneration and behavioral recovery following crush injury of the
      trigeminal root in lamprey.
AB  - In normal larval lamprey, bilateral application of horseradish peroxidase (HRP)
      to the dorsal part of the anterior oral hood labeled subpopulations of trigeminal
      components on both sides of the brain; peripherally projecting motoneurons,
      medullary dorsal cells (sensory), and spinal dorsal cells (sensory), as well as
      centrally projecting afferents in the trigeminal descending tracts. Following
      unilateral crush injury of the right trigeminal root, HRP labeling of sensory and
      motor trigeminal components on the right side gradually increased with increasing
      recovery time, between 2 weeks and 12 weeks postcrush (PC). Axons of trigeminal
      motoneurons appeared to exhibit robust regeneration, whereas restoration of
      projections in the descending trigeminal tract ipsilateral to the injury was
      incomplete. Control experiments indicated that motor and sensory axons from the
      intact side of the oral hood did not sprout across the midline to the denervated
      side. Several results suggested that regenerated trigeminal sensory fibers made
      synapses with brain neurons that have direct or indirect inputs to reticulospinal
      (RS) neurons. Following a unilateral crush injury of the right trigeminal root,
      escape behavior in response to stimulation of the right side of the oral hood
      gradually returned to normal. Muscle recordings at various recovery times
      confirmed that anatomical regeneration of trigeminal sensory axons was
      functional. In addition, at 8 or 12 weeks PC, brief stimulation of the oral hood
      ipsilateral or contralateral to the crush injury elicited synaptic responses in
      RS neurons on either side of the brain, similar to that in normal animals. In the
      lamprey, compensatory mechanisms probably allow recovery of behavioral function
      despite incomplete regeneration of trigeminal sensory axons within the central
      nervous system.

PMID- 9624588
TI  - Fine structure and development of dorsal root ganglion neurons and Schwann cells
      in the newborn opossum Monodelphis domestica.
AB  - The aim of these experiments was to determine the state of maturity of dorsal
      root ganglia and axons in opossums (Monodelphis domestica) at birth and to assess
      quantitatively changes that occur in early life. Counts made of dorsal root
      ganglion cells at cervical levels showed that the numbers were similar in newborn
      and adult animals, approximately 1,600 per ganglion. In cervical dorsal root
      ganglia of newborn animals, division of neuronal precursors cells had ceased. The
      number of axons in cervical dorsal roots was similar in newborn and adult animals
      (about 4,500). For each ganglion cell body, approximately three axons were
      counted in the dorsal root. At birth, dorsal roots contained several bundles
      about 30 microns in diameter consisting of small axons (0.05-2 microns in
      diameter). A few non-neural cells were identified as Schwann cell perikarya, each
      enclosing a number of neurites. Later, marked changes occurred in Schwann cells
      and in their relationship to axons in the roots. Thus, at 12 days, an increase
      occurred in the number of Schwann cells and fibroblasts, and the bundles had
      enlarged to about 80 microns with little increase in axon diameter (0.1-2
      microns). By 18 days, the bundles were larger, and myelination had already
      started. At 23 days, the dorsal root contained more than 500 myelinated axons
      that could reach 5 microns in diameter. The adult dorsal root enclosed about 900
      myelinated axons. Throughout this time, the relationship between the Schwann
      cells and axons changed. Together, these results indicate that the number of
      axons and cell bodies of sensory dorsal root ganglia in opossum do not show major
      changes after birth. In addition, these results set the stage for quantitative
      studies of regeneration of dorsal column fibers in injured neonatal opossum
      nervous system.

PMID- 9624589
TI  - GABAA and GABAC receptors on mammalian rod bipolar cells.
AB  - Rod bipolar (RB) cells of mammalian retinae receive synapses from different gamma
      aminobutyric acid (GABAergic) amacrine cells in the inner plexiform layer (IPL).
      We addressed the question whether RB cells of the rabbit and of the rat retina
      express different types of GABA receptors at these synapses. RB cells were
      immunolabeled in vertical sections of rat retinae with an antibody against
      protein kinase C (PKC). The sections were double-labeled for the alpha 1, alpha
      2, alpha 3, or gamma 2 subunits of the GABAA receptor. Punctate
      immunofluorescence, which represents synaptic localization, was found for all
      four subunits. Many of the alpha 1-, alpha 3-, or gamma 2-immunoreactive puncta
      coincided with the axon terminals of the PKC-immunolabeled RB cells. Sections and
      wholemounts of rabbit retinae were also double labeled for PKC and the rho
      subunits of the GABAC receptor. Rabbit RB cells were decorated by many rho
      immunoreactive puncta, which were shown by electron microscopy to represent
      synaptic localization. Previous work from our laboratory has shown that the alpha
      1, alpha 2, alpha 3, and rho subunits are not found within the same synapse but
      are expressed at different synaptic sites. Taken together, these results suggest
      that RB cells of mammalian retinae express at least three different types of GABA
      receptors at synaptic sites in the IPL: GABAC receptors, GABAA receptors
      containing the alpha 1 subunit, and GABAA receptors containing the alpha 3
      subunit.

PMID- 9624590
TI  - Expression of rat target of the antiproliferative antibody (TAPA) in the
      developing brain.
AB  - The present study defines the expression pattern of TAPA (target of the
      antiproliferative antibody, also known as CD81) in the developing rat brain. TAPA
      is a member of the tetramembrane spanning family of proteins, and like other
      members of this family it appears to be associated with the stabilization of
      cellular contacts (Geisert et al. [1996] J. Neurosci. 16:5478-5487). On
      immunoblots of the brain, TAPA is present in higher levels than any other tissue
      examined: muscle, tendon, peripheral nerve, cartilage, liver, kidney, skin, and
      testicle. Immunohistochemical methods were used to define the distribution of
      TAPA in the brain. This protein is expressed by ependyma, choroid plexus,
      astrocytes, and oligodendrocytes. TAPA is dramatically upregulated during early
      postnatal development, at the time of glial birth and maturation. At embryonic
      day 18, the levels of TAPA are low, with most of the immunoreaction product being
      associated with the ependyma, choroid plexus, and the glia limitans. As
      development continues, the amount of TAPA expressed in the brain increases, and
      at postnatal day 14 the levels approach those of the adult. This increase in the
      levels of TAPA at postnatal day 14 is due to upregulation in the gray matter and
      white matter. Thus, TAPA is found in all glial cells, and the level of this
      protein correlates with their maturation.

PMID- 9624591
TI  - Thalamic connections of the dorsomedial visual area in primates.
AB  - The dorsomedial visual area (DM) of owl monkeys is a cortical area that has been
      described recently in a range of primate species. To study the thalamic
      connections of this area, injections of several distinguishable neuroanatomical
      tracers were placed into DM in galagos, owl monkeys, squirrel monkeys, and
      macaque monkeys. The distribution of label was remarkably consistent across these
      diverse primate species. Labeled connections were densest within the pulvinar
      complex. Both the lateral and inferior divisions of the pulvinar, but not the
      medial division, had connections with DM. Within the inferior pulvinar of
      monkeys, central lateral and central medial nuclei had dense connections, and the
      medial and posterior nuclei had sparse connections with DM. Sparser connections
      were revealed in the lateral geniculate nucleus and the nucleus limitans.
      Anterograde label was also found in the superior colliculus. The consistencies in
      the pattern of subcortical projections across prosimian primates, New World
      monkeys, and Old World monkeys support the concept that DM is a visual area
      common to all primates. In addition, these results provide further evidence for
      proposed subdivisions of the inferior pulvinar.

PMID- 9624592
TI  - Bottlebrush dendritic endings and large dendritic fields: motion-detecting
      neurons in the tectofugal pathway.
AB  - In avian and mammalian brains, visual information from the retina is conveyed to
      the telencephalon via two separate pathways: the thalamofugal and the tectofugal
      pathways. Recently, Karten et al. ([1997] J. Comp. Neurol. 387:449-465) examined
      a portion of the tectofugal pathway, the projection from the optic tectum to the
      nucleus rotundus thalami, in pigeons. They defined two distinct subpopulations of
      tectal neurons projecting from the stratum griseum centrale (SGC; tectal layer
      13) to specific divisions of the rotundus. The goal of this study in chick was to
      verify the existence of the type I and type II SGC neurons, as defined by Karten
      et al., and then examine in greater detail the connectivity and morphology of
      these SGC neurons. Furthermore, our results suggest how the unique morphological
      characteristics of SGC neurons contribute to the large receptive fields (20-50
      degrees) found in physiological recordings and the SGC neuronal response to
      extremely small (ca. 0.05 degree), fast-moving (100 degrees/second) stimuli. By
      injecting retrograde tracer into various divisions of the chick rotundus, we
      verified that, indeed, the chick did possess type I and type II SGC neurons, as
      well as a "new" type of SGC neuron, type III, that is not found in the pigeon. We
      then used intracellular cell-filling techniques to define further these three
      types of SGC neurons. Our examination revealed the following: Type I SGC neurons
      had large, circular dendritic fields (average diameter, 1,725 microns) composed
      of smooth dendrites and ending in spine-rich, bottlebrush endings located in
      retinorecipient tectal layer 5b; type II SGC neurons had elliptical dendritic
      fields (average 1,447 microns) and dendritic endings located never more
      superficially than tectal layer 8; and type III SGC neurons had large dendritic
      fields (average 1,800 microns) of unknown shape and bottlebrush dendritic endings
      located in retinorecipient tectal layer 4. We suggest that the neuronal features
      of the SGC neurons (i.e., bottlebrush dendritic endings and large dendritic
      fields) are key morphological characteristics for the detection of motion within
      the tectofugal pathway. Furthermore, because neurons with similar morphology have
      also been found in the tecta of both mammals and reptiles, we suggest that these
      neuronal features are fundamental components of a phylogenetically conserved
      system used for the "extrastriate" detection of motion in vertebrates.

PMID- 9624593
TI  - Effects of intracerebroventricular administration of atrial natriuretic peptide
      (ANP) on blood pressure, heart rate and plasma ADH and corticosterone levels in
      normal and dehydrated rabbits.
AB  - In order to investigate the effects of centrally administered Atrial Natriuretic
      Peptide (ANP) on plasma ADH and corticosterone levels as well as on blood
      pressure and on heart rate, 20 male New Zealand White (NZW) rabbits were used.
      Measurements were made on restrained conscious animals one week after the
      implantation of an indwelling intracerebroventricular (i.c.v.) cannula and two
      indwelling intravascular catheters (intracarotid and intrajugular). Animals were
      classified into two main groups, those with water available ad libitum
      ("euhydrated" group) and those who were dehydrated for 24h ("dehydrated" group)
      before blood pressure and heart rate recordings and blood sampling for hormonal
      determination. Each group's individuals were divided into two subgroups of five
      animals each. Blood samples were collected at 0 min (control) and 30; 60, 90, 120
      min following i.c.v. administration of 25 microliters of either artificial
      cerebrospinal fluid (aCSF) (subgroups "aCSF") or human (h) ANP (1 microgram) in
      aCSF (25 microliters) (subgroups "hANP"). Blood pressure and heart rate were also
      recorded at the same times. Plasma ADH and corticosterone concentrations were
      determined by RIA. The results were analysed by ANOVA. Blood pressure and heart
      rate values were unaffected by water deprivation or by ANP administration. Mean
      plasma corticosterone levels at all times (30-120 min) were significantly higher
      (p < 0.001) than at 0 min time. Plasma corticosterone levels in the "dehydrated +
      aCSF" group were significantly higher (p < 0.05) than in each of the other groups
      ("dehydrated + hANP", "euhydrated + aCSF", "euhydrated + hANP"). Plasma
      corticosterone levels in each of those other groups did not differ significantly
      from one another. Dehydration resulted in an increase in ADH levels (p < 0.0001)
      and i.c.v. administration of hANP prevented (p < 0.05) in "dehydrated + hANP"
      experimental group, the increase in ADH levels observed in the control
      "dehydrated + aCSF" group from 90 to 120 min. The increase of corticosterone and
      ADH in the control dehydrated groups could possibly be due to the combined stress
      stimulus of dehydration and restriction in the restrain box. These results
      indicate that centrally administered ANP, at the concentration achieved in the
      present study, neither affects blood pressure and heart rate in conscious
      restrained euhydrated and 24h-dehydrated NZW rabbits nor decreases the ADH and
      corticosterone response to dehydration, but does apparently modulate ADH and
      corticosterone responses to other stimuli in the dehydrated state. In conclusion,
      the results of this study confirm that brain ANP may have an inhibitory effect on
      stimulated ADH and corticosterone release.

PMID- 9624594
TI  - The influence of dexamethasone treatment of pregnant rats on the development of
      chromaffin tissue in their offspring during the fetal and neonatal period.
AB  - The aim of these examinations was to determine the influence of dexamethasone
      (Dx)-treatment of gravid females, on day 16 of gestation on the development of
      medullary chromaffin tissue of their fetuses and neonatal offspring. In
      conducting these investigations we used stereological as well as
      spectrofluorimetric measurements, in 20-day-old fetuses and 1-, 3-, 5-, 7-, 9-,
      11-, 13- and 14-day-old neonatal rats. Single Dx-treatment (1.5 mg/kg bw) of the
      dams led to a significant decrease in body and adrenal weight of their fetuses
      and neonatal offspring, and also reduction of the medullary volume and the number
      of chromaffin cells during the entire period examined as a result of decreased
      cell proliferation in the fetal and early neonatal period (till the 5th day of
      age). The proliferative activity of the chromaffin cells was evaluated through
      the mitotic index after applying the cytostatic vincristine-sulphate. During the
      second neonatal week the mitotic index showed significantly higher values in
      comparison with the corresponding controls, which indicates that there is
      regeneration and recovery of the adrenal gland medulla. Adrenaline content in the
      adrenal gland tissue of offspring of Dx-treated dams was significantly reduced
      only on the 1st neonatal day. Thus, the change in blood glucocorticoid level of
      pregnant females after a single Dx injection during the period critical for
      development of the hypothalamo-pituitary-adrenal system in fetuses affects the
      development and kinetics of medullar chromaffin cell division.

PMID- 9624595
TI  - Urinary cortisol metabolites in the assessment of peripheral thyroid hormone
      action: overt and subclinical hypothyroidism.
AB  - Biological assessment of peripheral thyroid hormone action may be important in
      subclinical hypothyroidism, where decision-making is often difficult. The
      impairment of urinary cortisol metabolites in overt hypothyroidism reflects an
      acquired 11 beta hydroxysteroid dehydrogenase (11 beta OHSD) deficiency, and is
      assessed in terms of a reduction in the tetrahydrocortisone
      (THE)/tetrahydrocortisol (THF) ratio or THE/THE + alpha THF ratio; the alpha
      THF/THF ratio reflects 5 beta reductase activity. The aim of this study was to
      determine if urinary cortisol metabolite ratios are a good index of peripheral
      thyroid hormone action in subclinical hypothyroidism. MATERIALS AND METHODS: the
      THE/THF, THE/THF + alpha THF and alpha THF/THF ratios were measured in 24 h urine
      samples from 3 groups of subjects: 1) 18 euthyroid subjects; 2) 25 patients with
      elevated serum TSH and low FT4 levels (overt hypothyroidism); and 3) 25 patients
      with increased serum TSH and normal FT4 levels (subclinical hypothyroidism.
      RESULTS: 7/25 overtly and 5/25 subclinically hypothyroid patients had a THE/THF +
      alpha THF ratio below the mean control value -2 SD, while respectively 20/25 and
      11/25 patients had a THE/THF ratio below the mean control value -2 SD. The mean
      THE/THF + alpha THF, THE/THF and alpha THF/THF ratios were significantly
      different among the 3 groups (ANOVA) and were lower in the overtly hypothyroid
      group than in the other two groups (Fisher's test); daily urine sodium output was
      also significantly different between the three groups and lower in the overtly
      and subclinically hypothyroid groups than in the control group (Fisher's test).
      FT3 and FT4 both correlated with THE/THF + alpha THF in the overtly hypothyroid
      patients (r = 0.43; p < 0.05 and r = 0.40; p < 0.05, respectively). In the
      subclinically hypothyroid patients, TSH correlated with THE/THF + alpha THF (r =
      0.44; p < 0.05) and THE/THF (r = 0.43; p < 0.05). FT3, FT4 and TSH levels
      correlated with THE/THF + alpha THF (p < 0.001), THE/THF (p < 0.001), alpha
      THF/THF (p < 0.001) and daily natriuresis (p < 0.05) in the whole population
      (patients + controls). In conclusion, urinary cortisol metabolites, although
      impaired in overt hypothyroidism, are not an accurate index of peripheral thyroid
      hormone deficiency in subclinical hypothyroidism. We also identified an increase
      in the alpha THF/THF ratio in overt hypothyroidism, which may be related to 5
      beta reductase disturbances.

PMID- 9624596
TI  - Detection of a new de novo mutation at codon 251 of exon 8 of thyroid hormone
      receptor beta gene in an Italian kindred with resistance to thyroid hormone.
AB  - Resistance to thyroid hormone (RTH) is almost invariably associated with
      mutations of the thyroid hormone (TH) receptor beta (hTR beta) gene and is
      inherited as an autosomal dominant disease. Mutations of hTR beta identified in
      patients affected by RTH cluster generally at two spots of the ligand binding
      domain. We investigated whether an Italian kindred with RTH had a mutation in the
      thyroid hormone (TH) receptor beta gene. Blood samples were obtained from the
      available family members for biochemical and genetic analyses. Thyroid function
      tests in basal conditions, and in the case of the propositus also following
      incremental doses of T3, were performed. Exon 4 to 10 of hTR beta gene were
      amplified using the polymerase chain reaction (PCR) and the mutation was
      identified by direct sequence analysis. The affinity constant of this mutated
      receptor for T3 was measured by in vitro transcription-translation and was then
      compared with that of wild type. We identified a heterozygous G to A transition
      at nucleotide 1037 of exon 8 at codon 251, resulting in a glycine (G) to glutamic
      acid (E) substitution (G251E) in the patient affected by RTH and in his affected
      offspring, but not in the normal family members. This novel mutation represents a
      de novo mutation since both parents of the index case were unaffected and did not
      have this genomic mutation. When expressed in vitro, the mutant protein (G251E)
      showed a marked decrease of the affinity for T3, suggesting an impaired ligand
      dependent transactivation activity of this mutant receptor. In vivo studies with
      incremental doses of L-T3 demonstrated a reduced sensitivity to TH in the index
      case, in particular at the pituitary level where the thyrotrophs' activity was
      not completely inhibited even by 200 micrograms/day of L-T3. G251E mutation
      represents the fourth mutation described up to now in exon 8 of hTR beta among
      the subjects affected by RTH. A third cluster of mutations of the c-erbA beta
      gene located proximally with respect to the other two so far described begins to
      emerge in RTH patients.

PMID- 9624597
TI  - The changes of the thyroid function and serum testosterone levels after long-term
      L-NAME treatment in male rats.
AB  - Nitric oxide is a highly reactive gas that is produced by many tissues and exerts
      a series of physiological and pathophysiological effects. We studied the changes
      of the serum testosterone, thyroxine and thyrotropin levels, thyroid and anterior
      pituitary weights and thyroid cGMP concentrations in male Wistar strain rats
      treated with estradiol benzoate (EB) (1 mg/kg, im twice a week) and nonselective
      NO-synthase inhibitor L-NAME (N-omega-nitro-L-arginine methyl ester) alone and
      with combination of these substances. We have found that L-NAME in a dose 100
      mg/kg/day but not in a dose 50 mg/kg/day increased the serum thyroxine and
      testosterone levels and in the case of testosterone in a higher dose partially
      blocked its drop when administered simultaneously with EB. The serum thyrotropin
      levels significantly fell after L-NAME and EB treatment. The cGMP thyroid levels
      changed only slightly in groups treated EB and L-NAME alone and were
      significantly decreased in group treated with combination of these substances.
      The nitric oxide thus seems to be an important modulator of thyroid and
      testicular function. The cGMP activation cascade is not probably involved in the
      nitric oxide induced changes of thyroid function.

PMID- 9624599
TI  - The effect of reducing proximal tubular fluid delivery on the rate of filtration
      of single nephrons.
AB  - The rate of delivery of tubular fluid from the proximal tubule (PT) is thought to
      reset nephron filtration rate (SNGFR). In micropuncture experiments in rats we
      tested this hypothesis by reducing the efflux from the PT by simultaneously
      "double collecting" (DC) tubular fluid from the early distal tubule (DT) and from
      the last convolution of the PT of the same nephrons. SNGFR measured by total
      collection of tubular fluid was 34 +/- 3 nl/min at the DT and 34 +/- 3 nl/min at
      the PT (p > 0.97, n = 42). The simultaneous collection from proximal and distal
      sampling site was performed between these two paired measurements. It yielded an
      average SNGFR of 40 +/- 3 nl/min (p < 0.02). This may be due to the collection,
      at the distal site, of the extra amount of inulin stored between distal and
      proximal pipette, prior to starting the aspiration of tubular fluid. Since this
      error would decrease in longer collections, the difference in SNGFR between
      single and double collections was plotted against the duration of collections. In
      fact it was negatively correlated with the sampling time (p < 0.01), indicating
      no difference in SNGFRs for collections > 4 minutes. Reduction and complete
      interruption of the delivery of native proximal tubular fluid to the Macula Densa
      does not seem to influence the measurement of SNGFR. Filtration rate is not
      significantly different when measured within few minutes at the DT and PT of the
      same nephrons.

PMID- 9624598
TI  - Lack of effect of hexarelin on TRH-induced TSH response in normal adult man.
AB  - The mechanism of action of the synthetic growth hormone (GH)releasing peptide
      hexarelin is not yet fully understood. Although a direct effect on pituitary
      cells has been demonstrated, the peptide is also active at hypothalamic level,
      where specific binding sites have been found. The observation that hexarelin acts
      synergistically with GH-releasing hormone (GHRH) in releasing GH has suggested
      that it might suppress endogenous somatostatin secretion. As somatostatin is also
      inhibitory on TSH secretion, to verify the occurrence of modifications of the
      somatostatinergic tone induced by hexarelin, we studied its effects on TRH
      induced TSH secretion. Seven normal subjects (4 women and 3 men aged 24-29 years)
      underwent the following tests on 3 different days: a) TRH (200 micrograms/l i.v.)
      + placebo; b) hexarelin (1 microgram/Kg bw i.v.) + placebo c) combined TRH +
      hexarelin administration. Hexarelin induced significant and similar increases in
      serum GH levels when given in combination either with placebo or with TRH (1217
      +/- 470 vs 986 +/- 208 micrograms/min/l p:NS), while no modifications of GH
      levels were seen after TRH + placebo. Serum TSH levels were unmodified by
      hexarelin + placebo injection. The TSH increase elicited by hexarelin + TRH was
      superimposable to that elicited by TRH + placebo (1124 +/- 530 and 1273 +/- 380
      mU/min/l respectively). Circulating PRL levels slightly increased after hexarelin
      + placebo too (897 micrograms/min/l), and the PRL response to hexarelin + TRH was
      slightly, although not significantly, greater than that observed after TRH +
      placebo (2680 +/- 1517 and 2243 +/- 1108 micrograms/min/l, respectively). In
      conclusion, our data show that hexarelin does not alter basal and TRH-stimulated
      TSH secretion, thus suggesting that it does not inhibit somatostatin release.
      Furthermore a modest PRL-releasing effect of this peptide has been confirmed.

PMID- 9624600
TI  - Hypothalamic amenorrhea and cardiovascular hormones: changes of plasma calcitonin
      gene-related peptide and atrial natriuretic peptide levels.
AB  - Typical modifications of cardiovascular activity and water and salt homeostasis
      throughout female reproductive life are well known. Differences in plasma levels
      of calcitonin gene-related peptide (CGRP) and atrial natriuretic peptide (ANP)
      have been observed in conditions characterized by different estrogenic levels,
      suggesting a correlation between female reproductive function and these
      cardiovascular hormones. The aim of our study was to investigate in hypothalamic
      amenorrhea the relationship between estrogen deficiency and plasma ANP and CGRP
      response to adaptive tests (saline infusion test and upright posture test,
      respectively). Women with hypothalamic amenorrhea (aged 18-28 years) (n = 6) and
      age-matched healthy controls (n = 6) underwent both functional tests. Plasma CGRP
      and ANP levels were measured by specific radioimmunoassays before and in course
      of the tests. Basal plasma CGRP levels of amenorrheic patients did not
      significantly differ from those of normal women, while basal plasma ANP levels
      were significantly higher compared to controls (p < 0.01). In amenorrheic women,
      plasma CGRP levels showed a significant increase in response to upright posture
      test, though lower than the increase observed in normal women. In contrast,
      saline infusion test determined a significant increase in plasma ANP levels only
      in control subjects. In women with hypothalamic amenorrhea, the altered response
      of CGRP and ANP to adaptive stimuli indicates a partial derangement in the
      control of the secretion of these cardiovascular hormones. Nevertheless, the
      differences between such modifications and those observed in other conditions of
      altered estrogenic levels, suggest that in amenorrheic women hypogonadism is not
      the major factor influencing CGRP and ANP response to adaptive stimuli.

PMID- 9624601
TI  - Plasma atrial natriuretic factor levels in the inferior petrosal sinus blood of
      patients with Cushing's disease before and after corticotropin-releasing hormone
      administration.
AB  - Atrial natriuretic factor (ANF) was suggested to be involved as neurohormone in
      the modulation of hypothalamus-pituitary-adrenal axis in humans. However, this
      role is still controversial and widely discussed. In order to evaluate whether
      ANF is secreted in the hypothalamus-pituitary system in humans, plasma ANF
      concentrations were assayed in samples collected in the inferior petrosal sinus
      (IPS) blood of patients subjected to IPS sampling for diagnostic purposes or
      neurosurgical indications. In this retrospective study were included 22 patients:
      10 with Cushing's disease (CD) and 12 patients with GH or PRL-secreting pituitary
      adenoma, used as control group. In the patients with CD, plasma ANF concentration
      was also assayed after CRH test (hCRH 100 micrograms as i.v. bolus with blood
      samples after 5, 10 and 15 min). Both in patients with CD and in patients with GH
      or PRL-secreting pituitary adenoma, no significant difference was found in
      plasma ANF levels between IPS ipsilateral (13.0 +/- 1.5 and 12.2 +/- 1.2 pmol/l)
      or controlateral (13.0 +/- 1.6 and 12.2 +/- 1.4 pmol/l) to the adenoma and
      peripheral blood (14.2 +/- 2.0 and 13.7 +/- 1.5 pmol/l, respectively). Similarly,
      no difference was found between the IPS ipsilateral and controlateral to the
      adenoma in both groups of patients. In patients with CD, CRH administration
      induced a significant increase of ACTH levels (periphery: 34.9 +/- 6.2 vs 11.5 +/
      2.3 pmol/l, p < 0.05) but it did not induce any significant change of plasma ANF
      levels (14.0 +/- 2.0 vs 13.4 +/- 1.4 pmol/l in the ipsilateral IPS and 13.4 +/-
      1.6 vs 13.4 +/- 1.5 pmol/l in the ipsilateral IPS and 13.4 +/- 1.6 vs 13.4 +/-
      1.5 pmol/l in the contralateral IPS). In conclusion, the lack of ANF
      concentration gradient between IPS and peripheral blood, the lack of any
      difference in ANF concentrations between patients with CD and acromegalics or
      hyperprolactinemics and the absence of ANF response to CRH administration do not
      support the hypothesis of a role for ANF as neurohormone involved in the
      hypothalamus-pituitary control and particularly in the hypothalamus-pituitary
      adrenal axis modulation in humans.

PMID- 9624602
TI  - Comparative study of the intestinal absorption of three salts of calcium in young
      and elderly women.
AB  - A daily ingestion of 1000 to 1500 mg elemental calcium associated with vitamin D
      supplement is presently considered to be the adequate and least expensive therapy
      for senile osteoporosis. There exists only scarce data about calcium absorption
      with available calcium salts in elderly patients. We have compared the digestive
      absorption of calcium (Ca) citrate in soluble and solid form and calcium
      gluconolactate-carbonate in 15 young and 20 elderly, healthy women using the oral
      calcium loading test. The subjects were divided into two groups. In the first
      group, the absorption of solid Ca citrate (1000 mg Ca element) was compared to
      the absorption of Ca gluconolactate-carbonate (1000 mg Ca element) both in young
      (n = 7) and elderly women (n = 10). In the second group, the absorption of
      soluble Ca citrate (1000 mg Ca element) was compared to the absorption of Ca
      gluconolactate-carbonate (1000 mg Ca element) in young (n = 8) and elderly (n =
      10) women. In the preload phase, basal calciuria was increased in elderly women
      (p < 0.01) although basal calcemia was similar in young and elderly women. After
      oral administration of the calcium salts, an increase in plasma Ca was observed
      in both groups which was greater for soluble Ca citrate and Ca gluconolactate
      than for solid Ca citrate. In young women, the increase in plasma calcium was
      significantly higher with soluble Ca citrate compared to Ca gluconolactate (p <
      0.05). In elderly women, the postload calciuria was significantly higher for
      soluble Ca citrate (p < 0.05) and Ca gluconolactate (p < 0.05) compared to solid
      Ca citrate. A similar pattern was observed in young women, although it was not
      significant. In conclusion, an oral load of 1000 mg soluble Ca citrate and Ca
      gluconolactate-carbonate induces significant biochemical changes suggesting a
      better digestive absorption compared to Ca citrate in solid form, both in young
      and elderly women. We did not observe different response, between young and old
      patients.

PMID- 9624603
TI  - Is the hypothalamic-pituitary-adrenal axis really hyperactivated in visceral
      obesity?

PMID- 9624604
TI  - Mutation of nucleotide 1,762 in the core promoter region during hepatitis B e
      seroconversion and its relation to liver damage in hepatitis B e antigen
      carriers.
AB  - In chronic hepatitis B virus (HBV) infection, mutations develop frequently at
      nucleotides 1,762/1,764 in the X protein open reading frame, where the core
      promoter is also located. By using a modified allele-specific polymerase chain
      reaction method, the longitudinal emergence of the A-->T mutation at nucleotide
      1,762 was studied in relation to precore mutations, genotype, and liver damage.
      First, samples from 38 carriers that were drawn before and after hepatitis B e
      (HBe) seroconversion were tested. T-1,762 mutant strains increased during HBe
      seroconversion (P = 0.004). In the HBe antigen-negative (HBeAg-) phase, T-1,762
      mutants were found in 71% (12 of 17) of patients without compared with 33% (6 of
      18) of patients with a concomitant precore mutation that prevents HBeAg synthesis
      (P = 0.08). Second, in 55 HBeAg+ patients, the T-1,762 mutant was found to be
      associated with more liver inflammation (P = 0.04) and fibrosis (P = 0.02), as
      measured by histology activity index (HAI) scores. The results show that the
      nucleotide (nt) 1,762 A-->T mutation often develops during HBe seroconversion,
      particularly in strains without precore mutations that prevent HBeAg production.
      For unknown reasons, the T-1,762 mutant was rare in genotype B strains. The
      presence of a T-1,762 mutant in the HBeAg+ phase may be useful for identifying
      immunoactivation in previously immunotolerant carriers, which could be valuable
      for selecting patients for interferon therapy.

PMID- 9624605
TI  - Effect of genotypes on the quantification of hepatitis C virus (HCV) RNA in
      clinical samples using the Amplicor HCV Monitor Test and the Quantiplex HCV RNA
      2.0 assay (bDNA).
AB  - The Amplicor HCV Monitor test and the Quantiplex HCV RNA 2.0 (bDNA) assay are two
      commercially available assays for the quantification of hepatitis C virus (HCV)
      RNA in clinical samples. A direct comparison of the two assays was carried out
      using sera frozen previously from patients known to be chronically infected with
      HCV. Overall, 61 samples from 51 patients were tested simultaneously by the two
      methods: 67% (28/42) of the patients were infected by HCV genotype/serotype 1,
      10% (4/42) with type 2, and 24% (10/42) with type 3. When the absolute value from
      each assay was examined, the Quantiplex assay gave a consistently higher reading
      and the mean logarithmic difference between the two assays was 1.4 (1.0 in type
      1, 2.0 in type 2, and 2.2 in type 3). When analyzed according to genotype, strong
      correlation was observed between the two assays for type 1 (r = 0.83, 95% CI 0.63
      0.93, P < 0.01), but not for nontype 1 samples. Despite the difference in
      absolute level reported by the two assays, there was a consistent trend of change
      in HCV RNA concentration by both assays in patients whose consecutive samples
      were analyzed and the differences between the two assays in consecutive samples
      were within 0.4 log of each other. The results suggested that with samples
      containing genotype 1, the Amplicor assay was more sensitive than the Quantiplex
      assay by about one log. However, the sensitivities of the two assays with nontype
      1 samples were much closer probably due to the failure of the Amplicor assay to
      quantify nontype 1 genotypes effectively.

PMID- 9624606
TI  - Experimental African HEV infection in cynomolgus macaques (Macaca fascicularis).
AB  - Experimental infection with hepatitis E virus (HEV) from Africa has not been
      investigated. Our purpose was to study hepatitis E produced by HEV from Chad
      (North Africa) and to analyze the genetic sequence of the HEV obtained after
      animal passage. An HEV-containing fecal sample from Chad was intravenously
      inoculated in four cynomolgus macaques. When serum Alanine Amino Transferase
      (ALT) levels rose, open liver biopsy and bile aspiration were performed. In all
      the monkeys, an ALT rise occurred 25 to 32 days after inoculation and new anti
      HEV was detected by Enzyme Immuno Assay (EIA). Hepatic histopathology was
      consistent with acute viral hepatitis. HEV was detected by polymerase chain
      reaction (PCR) in bile (3/4 animals) and feces (2/4 animals) and by imunoelectron
      microscopy (IEM) in the inoculum and one bile specimen. A genetic variant HEV was
      identified in one monkey. The Chad HEV produced hepatitis E with pathophysiologic
      and histopathologic findings similar to those observed with HEV from other
      geographic origins. A genomic variant HEV population was produced after one
      passage in a macaque.

PMID- 9624607
TI  - Sexual transmission of GB virus C/hepatitis G virus.
AB  - Although it is established that infection with GB virus C (GBV-C) or hepatitis G
      virus (HGV) can be transmitted parenterally, the prevalence of GBV-C/HGV viremia
      in the general population (2-5%) is relatively high compared with other
      parenterally borne viruses such as hepatitis C virus. To investigate the
      possibility of sexual transmission of GBV-C/HGV, we determined the frequency of
      viremia by the polymerase chain reaction and serological reactivity to the E2
      protein by ELISA in samples collected from individuals at risk for sexually
      transmitted diseases attending a city genitourinary medicine clinic. GBV-C/HGV
      viremia was detected in 27 of 87 male homosexuals (31%) and 9 of 50 prostitutes
      (18%), frequencies significantly greater than those in matched controls (2/63)
      and local blood donors (2.3%). Among nonviremic individuals, a high frequency of
      serological reactivity to the E2 protein of GBV-C/HGV was also observed in the
      risk groups (male homosexuals: 14/60; prostitutes: 11/41), although these figures
      are likely to be underestimates of the frequency of past infection as detectable
      anti-E2 reactivity may attenuate rapidly over time following resolution of
      infection. Infection with GBV-C/HGV was more frequent among those coinfected with
      human immunodeficiency virus type 1. Among male homosexuals from whom
      retrospective samples were available, evidence for de novo infection was found in
      9 of 22 individuals over a mean sampling time of 2.9 years, predicting an
      annualized incidence of GBV-C/HGV infection of approximately 11% in this group.
      The high prevalence and incidence of GBV-C/HGV infection in these individuals and
      prostitutes provides strong evidence for its spread by sexual contact. Further
      studies are required to investigate the mechanism of its transmission and the
      clinical significance of acute and persistent infection in these risk groups.

PMID- 9624608
TI  - A decreased production of IL12 in vitro is associated with isolation of
      cytopathic HIV-1 strains in HIV-1-infected patients.
AB  - The changes in type 1 (IL12, IFN gamma, IL2) and type 2(IL4, IL10) cytokine
      profiles may be associated with virological parameters of progression of the
      disease in HIV-1-infected patients. The production of cytokines was studied in
      LPS + PHA-activated whole-blood culture in HIV-1-infected individuals at
      different stages of the disease. The association was investigated between IL12p40
      and IL12p70 profiles and other cytokines (IFN gamma, IL4, IL10), as well as the
      isolation of cytopathogenic HIV-1 strains. The phenotype of HIV strains was
      studied by a micromethod based on P4 cell line, allowing detection of cytopathic
      effects of HIV-1 isolates (syncytium-induction and cell-killing without syncytium
      induction). The individual variations in IL12p40 and IL12p70 production were
      limited in the healthy controls. Low values were observed in HIV-1-infected
      patients. The production of IL12 (p40 and p70) and the IL12p70/IL4 ratio and the
      IFN gamma/IL4 ratio were significantly lower in patients with cytopathic isolates
      compared with patients with noncytopathic isolates, and a correlation was
      obtained between the values of IL12 (IL12p40 and IL12p70) and those of IFN
      gamma/IL4 ratio. There was no increase in the secretion of IL4 and IL10 in
      patients with cytopathic strains compared with other patients. The results
      indicate a decreased production of type 1 cytokines (IL12, IFN gamma) in the
      presence of a relatively preserved production of type 2 cytokines (IL4, IL10) in
      HIV-1-infected patients. In conclusion, the defect of production of IL12 by whole
      blood is associated with virological correlates of progression of HIV-1 disease.

PMID- 9624609
TI  - Treatment of classical Kaposi's sarcoma with intralesional injections of
      cidofovir: report of a case.
AB  - The effect of intralesional injections of cidofovir, a nucleotide analog with
      potent in vitro activity against human herpesvirus 8 (HHV-8), was studied in vivo
      in an HIV-negative patient with classical Kaposi's sarcoma (KS). After five
      weekly injections of the drug, no clinical, histological, immunohistological, or
      virological changes could be detected in comparison with saline-injected lesions.
      These findings suggest that, once the KS tumor has developed, active viral
      replication is no longer involved in the pathogenesis of the disease. Alternative
      hypotheses are that HHV-8 replication in blood-borne cells may foster growth of
      spindle cells in the skin, or that blocking HHV-8 may not affect existing lesions
      but may prevent new lesions from developing.

PMID- 9624610
TI  - Upregulation of Epstein-Barr virus-encoded latent membrane protein by human
      herpesvirus 6 superinfection of EBV-carrying Burkitt lymphoma cells.
AB  - The effect of HHV-6 strain A infection on the expression of Epstein-Barr virus-
      (EBV-) encoded growth transformation-associated genes in two EBV-positive Burkitt
      lymphoma cell lines, Akata and P3HR-3, was investigated. The results indicate
      that HHV-6A upregulates the expression of the latent membrane protein LMP-1 in
      both cell lines. Expression of EBNA-2 was also upregulated in Akata cells
      following HHV-6A infection. Transfection of reporter constructs carrying the LMP
      1 regulatory sequences (LRS; -634/+40) or its 5' deleted derivatives in Akata and
      in a T-lymphoblastoid cell line, J-Jhan, confirmed the presence of positive and
      negative regulatory elements responsive to HHV-6A infection in LMP-1 regulatory
      sequence (LRS). The majority of LRS constructs were under the influence of
      dominant negative factors. HHV-6A was able to override the effect of such factors
      acting on reporter plasmids containing the -634/-54, -324/-54, -214/-54, and 
      106/-54 parts of LRS. The plasmid that carried only the -54/+40 LRS region was
      constitutively active in both Akata and J-Jhan cells; in Akata, its activity was
      influenced by HHV-6A. The finding that HHV-6A infection may activate LMP-1 and
      EBNA-2 expression, which is essential for the immortalization of B-lymphocytes by
      EBV, shows a novel aspect of the interaction between these two herpesviruses.

PMID- 9624611
TI  - Epstein-Barr virus expression within keratinizing nasopharyngeal carcinoma.
AB  - Three stages of maturation can be seen in keratinizing nasopharyngeal carcinomas.
      These stages are similar morphologically to basal cells, intermediate and
      superficial squamous cells seen in normal squamous epithelium. Taking advantage
      of such a diverse tumour cell population, 10 keratinizing nasopharyngeal
      carcinoma (NPC) were examined by in situ hybridization for the presence of latent
      Epstein-Barr Virus (EBV) using EBV encoded RNAs (EBERs) and by immunohistology
      for the presence of EBV early antigen-diffuse (EA-D) and the 350/220 kd membrane
      glycoprotein of the EBV. The basal cell-like tumour cells are mainly infected
      latently with the virus; viral replication was found in isolated intermediate
      squamous cells, whilst superficial squamous cells are largely depleted of all the
      viral markers. We used a control series of nonkeratinizing nasopharyngeal
      carcinomas composed of undifferentiated and poorly differentiated tumour cells
      and EBV latency was present in these tumours. Viral replication was detected by
      RT-PCR, in the undifferentiated tumours but viral replication was not seen by
      immunohistology. The possible relationship between EBV life cycle in these
      tumours and tumour cell differentiation is discussed in the light of these
      findings.

PMID- 9624612
TI  - Seroepidemiological study of respiratory syncytial virus in Sao Paulo state,
      Brazil.
AB  - Transmission of respiratory syncytial virus is thought to be highly seasonal
      based on reported clinical cases, although transmission resulting in mild disease
      in all age groups has been little studied. This has been investigated in a
      seroepidemiological survey using sera from Sao Paulo, Brazil. Seroprevalence was
      found to increase rapidly with age, reaching over 90% by three years of age. This
      is typical of viral infections, which produce life-long immunity following
      primary infection. One-hundred percent seropositivity was attained by five years
      of age and maintained throughout adulthood, whereas mean antibody titers
      continued to increase with age. The mean duration of maternal antibodies was
      estimated to be 3.3 months with antibody decay demonstrated in paired samples
      from infants. The results are discussed in relation to possible mechanisms
      generating such a profile.

PMID- 9624613
TI  - Shell-vial culture and pp65 antigenemia assay in the detection of cytomegalovirus
      in the first blood sample of renal transplant recipients.
AB  - The aim of the study was to compare the efficacy of pp65 antigenemia assay and
      the shell-vial culture (SVC; viremia) for the diagnosis of cytomegalovirus (CMV)
      infection in renal transplant recipients, comparing the results obtained in the
      first blood sample and the total number of blood samples analyzed in this group
      of patients. During the study period, 70 renal transplant recipients were
      studied: 44 (62.8%) with CMV infection. The method of sedimentation in a dextran
      solution for leukocyte extraction was used in the pp65 antigenemia assay. The MRC
      5 shell-vial assay was used for CMV isolation from leukocytes (viremia). Eighty
      blood samples were examined from 70 renal transplant recipients: Of the 44
      positive samples studied, in 77.5% of cases, both the antigenemia assay and the
      SVC were positive. In 16.2%, only the antigenemia assay was positive, and, in
      6.2%, only the SVC was positive. In all blood samples studied, the antigenemia
      was present in 93.7% of cases, and the SVC was present in 83.7% (P = 0.04). If
      the results obtained in only the first blood sample taken for the diagnosis are
      studied, then we observe that the antigenemia assay was positive in 39 patients
      (88.6%), whereas the SVC was positive in 41 patients (93.1%), although the
      difference was not statistically significant (P = 0.39). It is concluded that the
      inoculation of all of the leukocytes extracted from blood samples in the SVC
      seems to produce a slight increase in the sensitivity of the cell culture and
      that the SVC becomes positive before the antigenemia for the detection of CMV in
      peripheral blood, especially in the first blood sample.

PMID- 9624614
TI  - Absence of detectable measles virus genome sequence in inflammatory bowel disease
      tissues and peripheral blood lymphocytes.
AB  - A highly sensitive measles-specific RT-PCR-nested PCR system was established,
      which consistently amplified measles virus genome sequence from control samples
      containing as little as 5.5 x 10(-3) pfu per reaction. This method failed to
      detect the presence of measles virus in 93 colonoscopic biopsies and 31
      peripheral blood lymphocyte preparations, examined and obtained from patients
      with inflammatory bowel disease (IBD) and noninflammatory controls. All patients
      had detectable levels of serum neutralization antibody against measles virus.
      Each biopsy was estimated to have about one million cells, based on the
      amplification of the beta actin gene. The assay was calibrated by use of a known
      number of lymphocytes. The method applied was able to amplify measles virus RNA
      from a nucleic acid mixture equivalent to 18 cells derived from subacute
      sclerosing panencephalitis (SSPE) brain material. The level of measles RNA
      present, if any, in the biopsies is therefore at least 50,000-fold less than in
      SSPE.

PMID- 9624615
TI  - Acyclovir-resistant varicella-zoster virus: phenotypic and genetic
      characterization.
AB  - A man with acquired immunodeficiency syndrome (AIDS) developed zoster of the
      right arm which was resistant clinically to acyclovir. Varicella-zoster virus
      (VZV) was cultured from a skin biopsy performed at the beginning of acyclovir
      therapy (isolate 1) and after its failure (isolate 2). The emergence of acyclovir
      resistance during treatment was investigated by developing a simple and rapid
      drug sensitivity assay based on the plaque reduction reference method. This late
      antigen synthesis reduction assay involved serial dilutions of cell-associated
      virus. The 50% inhibitory concentration (IC50) of acyclovir was 16 +/- 7.5 microM
      for the susceptible reference strain OKA, in agreement with published data. The
      acyclovir IC50 increased from 6.5 microM for isolate 1 to 100 microM for isolate
      2. In comparison with the sequence of isolate 1, isolate 2 had a single mutation
      consisting of a C to T change at position 907 of the thymidine kinase gene, which
      changed a glutamine codon into a stop codon at position 303 of the thymidine
      kinase protein. These results show the emergence of acyclovir resistance through
      a single previously undescribed mutation in the thymidine kinase gene, and
      confirm the heterogeneity of mutations inducing acyclovir resistance.

PMID- 9624617
TI  - Short day lengths delay development of the SNB neuromuscular system in the
      Siberian hamster, Phodopus sungorus.
AB  - The Siberian hamster, Phodopus sungorus, breeds seasonally. In the laboratory,
      the seasonal breeding can be controlled by photoperiod, which affects the
      durations of nightly melatonin secretions. Winterlike short day lengths induce
      gonadal regression in adult animals, and pups born and maintained in short days
      undergo gonadal development much later than animals born into long days. The
      spinal nucleus of the bulbocavernosus (SNB) and its target muscles, the
      bulbocavernosus (BC) and levator ani (LA), comprise a sexually dimorphic,
      androgensensitive neuromuscular system involved in male reproduction. The SNB
      neuromuscular system was studied in male Siberian hamsters maintained from
      conception in short-day (8:16 h light/dark cycle) versus long-day (16:8 h
      light/dark cycle) conditions. At 40-47 days of age, development of three
      components of the SNB neuromuscular system were all significantly delayed in
      hamsters raised in the short photoperiod: BC/LA muscle weight, the size of SNB
      motoneuronal somata, and the area of the neuromuscular junctions at the BC/LA
      muscles of short-day hamsters were each significantly reduced relative to those
      of longday counterparts. Thus, development of the SNB reproductive system is
      delayed under short day lengths in this species.

PMID- 9624616
TI  - Development of LBP110 expression by neural crest-derived enteric precursors:
      migration and differentiation potential in ls/ls mutant mice.
AB  - Neural crest-derived cells acquire a 110-kD laminin-binding protein (LBP110) when
      they colonize the murine bowel. Laminin stimulates LBP110-expressing cells to
      develop as neurons. We have followed the development of LBP110 by neural crest
      derived cells as they enter the gut of control and ls/ls mutant mice. The
      expression of neurofilament and choline acetyltransferase was used as markers of
      a neuronal phenotype. Tyrosine hydroxylase was used as a marker for the mash-1
      dependent lineage of enteric precursors, while calcitonin gene-related peptide
      was used as a marker for the mash-1-independent lineage of crest-derived cells. A
      subset of cells expressing LBP110 was located along the vagi at E10 at cervical
      and thoracic levels. At E12, cells expressing LBP110 extended from the foregut to
      the midgut. The expression of neurofilament protein lagged behind that of LBP110
      by about 0.5 day and then became coincident with LBP110 immunoreactivity. By E15,
      cells doubly labeled with antibodies to LBP110 and neurofilament protein were
      located along the entire extent of the bowel up to but not including the terminal
      colon. By E16, both the proximal and terminal colon contained cells expressing
      LBP110 and neurofilaments. The pattern of immunoreactivity could not be
      distinguished between ls/ls and control animals prior to E16. By E16, when the
      terminal colon of control animals contained many cells expressing LBP110 and
      neurofilaments, the terminal colon of ls/ls animals lacked cells expressing these
      proteins; nevertheless, structures outside of the terminal colon were heavily
      endowed with cells expressing LBP110 and neurofilaments. These ectopically
      located cells derived from both mash-1-dependent and -independent lineages of
      crest-derived precursors.

PMID- 9624618
TI  - CEP-1347/KT7515 prevents motor neuronal programmed cell death and injury-induced
      dedifferentiation in vivo.
AB  - CEP-1347, also known as KT7515, a derivative of a natural product
      indolocarbazole, inhibited motor neuronal death in vitro, inhibited activation of
      the stress-activated kinase JNK1 (c-jun NH terminal kinase) in cultured spinal
      motor neurons, but had no effect on the mitogen-activated protein kinase ERK1 in
      these cells. Results reported here profile the functional activity of CEP
      1347/KT7515 in vivo in models of motor neuronal death or dedifferentiation.
      Application of CEP-1347/KT7515 to the chorioallantoic membrane of embryonic
      chicks rescued 40% of the lumbar motor neurons that normally die during the
      developmental period assessed. Peripheral administration of low doses (0.5 and 1
      mg/kg daily) of CEP-1347/KT7515 reduced death of motor neurons of the spinal
      nucleus of the bulbocavernosus in postnatal female rats, with efficacy comparable
      to testosterone. Strikingly, daily administration of CEP-1347/KT7515 during the 4
      day postnatal window of motor neuronal death resulted in persistent long-term
      motor neuronal survival in adult animals that received no additional CEP
      1347/KT7515. In a model of adult motor neuronal dedifferentiation following
      axotomy, local application of CEP-1347/KT7515 to the transected hypoglossal nerve
      substantially reduced the loss of choline acetyl transferase immunoreactivity
      observed 7 days postaxotomy compared to untreated animals. Results from these
      experiments demonstrate that a small organic molecule that inhibits a signaling
      pathway associated with stress and injury also reduces neuronal death and
      degeneration in vivo.

PMID- 9624619
TI  - Specific projections of sympathetic preganglionic neurons are not intrinsically
      determined by segmental origins of their cell bodies.
AB  - Sympathetic preganglionic projections of the chick are segmentally specific.
      Neurons from the 16th cervical (C16) and the first thoracic (T1) spinal cord
      segments project almost exclusively in the rostral direction, while those from
      the fifth thoracic (T5) to the first lumbar (L1) spinal segments project almost
      exclusively in the caudal direction. Neurons from the intervening spinal cord
      segments (T2-4) project in rostral and caudal directions. There is also a
      tendency for rostrally located neurons in each segment to project rostrally and
      caudally located neurons to project caudally. To investigate whether specific
      projections of preganglionic neurons are intrinsically determined by segmental
      origins of their cell bodies, neural tube segments were transplanted or rotated
      in embryos at stages 19-26; these stages include times during and after
      preganglionic cell birth and just prior to axon outgrowth. When the T1 neural
      tube segment was replaced with the T5 or T7 neural tube segment the transplanted
      T5 or T7 preganglionic neurons, now in the T1 position, projected rostrally.
      Conversely, when the T5 or T7 neural tube segment was replaced with the T1 neural
      tube, the transplanted T1 preganglionic neurons projected caudally. In addition,
      when individual T3 spinal cord segments were rotated 180 degrees along the A-P
      axis, neurons which were originally in the caudal part of the segment projected
      rostrally, whereas neurons originally from the rostral part of the segment
      projected caudally. These results show that specific projections of preganglionic
      neurons are not intrinsically determined by segmental origins of their cell
      bodies.

PMID- 9624620
TI  - Growth preferences of adult rat retinal ganglion cell axons in retinotectal
      cocultures.
AB  - We examined whether regenerating axons from adult rat ganglion cells are able to
      recognize their appropriate target region in vitro. Explants from adult rat
      retina were cocultured with embryonic sagittal midbrain slices in Matrigel. The
      midbrain sections contained the superior colliculus, the main target for retinal
      ganglion cell axons in rats, and the inferior colliculus. We observed a
      statistically significant preference of both temporal and nasal retinal axons to
      grow toward their appropriate target region (anterior and posterior superior
      colliculus, respectively). No preferential growth of retinal ganglion cell axons
      was detected in controls, for which retinal explants were cultured on their own.
      When retinal ganglion cell axons were given a choice between superior colliculus
      and inferior colliculus, axons from nasal retina preferentially grew toward the
      posterior superior colliculus and avoided the inferior colliculus. In contrast,
      temporal axons in the same assay did not show preference for either of the
      colliculi. These findings suggest that regenerating axons from adult rat retina
      are able to recognize target-specific guidance cues released from embryonic
      midbrain targets in vitro.

PMID- 9624622
TI  - In vitro survival and differentiation of neurons derived from epidermal growth
      factor-responsive postnatal hippocampal stem cells: inducing effects of brain
      derived neurotrophic factor.
AB  - Neural stem cells proliferate in vitro and form neurospheres in the presence of
      epidermal growth factor (EGF), and are capable of differentiating into both
      neurons and glia when exposed to a substrate. We hypothesize that specific
      neurotrophic factors induce differentiation of stem cells from different central
      nervous system (CNS) regions into particular fates. We investigated
      differentiation of stem cells from the postnatal mouse hippocampus in culture
      using the following trophic factors (20 ng/mL): brain-derived neurotrophic factor
      (BDNF), neurotrophin-3 (NT-3) and glial-derived neurotrophic factor (GDNF).
      Without trophic factors, 32% of stem cells differentiated into neurons by 4 days
      in vitro (DIV), decreasing to 10% by 14 DIV. Addition of BDNF (starting at either
      day 0 or day 3) significantly increased neuron survival (31-43% by 14 DIV) and
      differentiation. Morphologically, many well-differentiated neurons resembled
      hippocampal pyramidal neurons. 5'-Bromodeoxyuridine labeling demonstrated that
      the pyramidal-like neurons originated from stem cells which had proliferated in
      EGF-containing cultures. However, similar application of NT-3 and GDNF did not
      exert such a differentiating effect. Addition of BDNF to stem cells from the
      postnatal cerebellum, midbrain, and striatum did not induce these neuronal
      phenotypes, though similar application to cortical stem cells yielded pyramidal
      like neurons. Thus, BDNF supports survival of hippocampal stem cell-derived
      neurons and also can induce differentiation of these cells into pyramidal-like
      neurons. The presence of pyramidal neurons in BDNF-treated hippocampal and
      cortical stem cell cultures, but not in striatal, cerebellar, and midbrain stem
      cell cultures, suggests that stem cells from different CNS regions differentiate
      into region-specific phenotypic neurons when stimulated with an appropriate
      neurotrophic factor.

PMID- 9624621
TI  - Nitric oxide donors inhibit the acetylcholine-induced Cl- current in identified
      Onchidium neurons.
AB  - The present study was undertaken to assess the effects of sodium nitroprusside
      (SNP) and diethylamine NO (C2H5)2N[N(O)NO]-Na+ (DEA/NO), NO donors, on an
      acetylcholine (ACh)-induced Cl- current in identified Onchidium neurons using
      voltage-clamp and pressure ejection techniques. Bath-applied SNP (10 microM) and
      DEA/NO (5-10 microM) reduced the ACh-induced Cl- current in the neurons without
      affecting the resting membrane conductance and holding current. The suppressing
      effect of NO donors were concentration-dependent and completely reversible.
      Pretreatment with 1H-[1,2,4]oxadiazolo-[4,3-a] quinoxalin-1-one (1 micro M), a
      specific inhibitor of NO-stimulated guanylate cyclase, and hemoglobin (50 micro
      M), a nitric oxide scavenger, decreased the SNP-induced inhibition of the ACh
      induced current. Intracellular injection of guanosine 3',5'-cyclic monophosphate
      (cGMP) or bath-application of 3-isobutyl-1-methylxanthine (50 micro M), a non
      specific phosphodiesterase inhibitor, inhibited the ACh-induced current,
      mimicking the effect of NO donors. These results suggest that SNP and DEA/NO
      inhibit the ACh-induced Cl- current and that this effect is mediated by an
      increase in intracellular cGMP.

PMID- 9624623
TI  - Distribution of synaptic vesicle proteins within single retinotectal axons of
      Xenopus tadpoles.
AB  - In the developing retinotectal projection, retinal axon arbor structure changes
      rapidly within the target tectal neuropil at stages when the visual system
      functions to process visual information. In vivo imaging of single retinotectal
      axon arbors shows that up to 50% of the arbor branch length can be restructured
      within 8 h and short branchtips have average lifetimes of 10 min. To determine if
      presynaptic sites are restricted to the relatively stable part of the arbor or if
      they are also located on the more dynamic portions of the arbor, punctate
      staining of synaptic vesicle proteins (SVP) synapsin 1 and synaptophysin was
      mapped within individual retinal axons using double-label confocal
      immunocytochemistry. We report that SVP puncta were distributed throughout the
      retinotectal axon arbor. Notably, short branchtips, which are known to be
      extremely dynamic, contain the presynaptic machinery necessary for synaptic
      transmission. These data support a model in which activity-dependent mechanisms
      can influence presynaptic axon arbor morphology by modifying the rate of dynamic
      rearrangements of axonal branchtips.

PMID- 9624624
TI  - Adenoviral vector-mediated gene delivery to injured rat peripheral nerve.
AB  - Although much progress has been made, current treatments of peripheral nerve
      damage mostly result in only partial recovery. Local production of neurite
      outgrowth-promoting molecules, such as neurotrophins and/or cell adhesion
      molecules, at the site of damage may be used as a new means to promote the
      regeneration process. We have now explored the ability of an adenoviral vector
      encoding the reporter gene LacZ (Ad-LacZ) to direct the expression of a foreign
      gene to Schwann cells of intact and crushed rat sciatic nerves. Infusion of 8 x
      10(7) PFU Ad-LacZ in the intact sciatic nerve resulted in the transduction of
      many Schwann cells with high levels of transgene expression lasting at least up
      to 12 days following viral vector administration. The efficacy of adenoviral
      vector delivery to a crushed nerve was investigated using three strategies.
      Injection of the adenoviral vector at the time of, or immediately after, a crush
      resulted in the transduction of only a few Schwann cells. Administration of the
      adenoviral vector the day after the crush resulted in the transduction of a
      similar number of Schwann cells 5 days after administration, as observed in
      uncrushed nerves. Regenerating nerve fibers were closely associated with beta
      galactosidase-positive Schwann cells, indicating that the capacity of transduced
      Schwann cells to guide regenerating fibers was not altered. These results imply
      that the expression of growth-promoting proteins through adenoviral vector
      mediated gene transfer may be a realistic option to promote peripheral nerve
      regeneration.

PMID- 9624625
TI  - Soluble ICAM-1 in CSF coincides with the extent of cerebral damage in patients
      with severe traumatic brain injury.
AB  - The intercellular adhesion molecule-1 (ICAM-1) expressed by endothelial cells is
      crucial in promoting adhesion and transmigration of circulating leukocytes across
      the blood-brain barrier (BBB). Migrated immunocompetent cells, in turn, release
      mediators that stimulate glial and endothelial cells to express ICAM-1 and
      release cytokines, possibly sustaining cerebral damage. Following activation,
      proteolytic cleavage of membrane-anchored ICAM-1 results in measurable levels of
      a soluble form, sICAM-1. The aims of this study were to investigate the changes
      of sICAM-1 levels in ventricular CSF and serum and to elucidate the influence of
      structural brain damage as estimated by computerized tomography (CT) as well as
      the extent of BBB dysfunction as calculated by the CSF/serum albumin ratio (QA)
      in patients with severe traumatic brain injury (TBI). All investigated parameters
      revealed two subgroups. Patients belonging to group A had sICAM-1 levels in CSF
      above normal range, presented marked cerebral damage and a disturbance of the BBB
      (range 0.6-24.7 ng/ml, n = 8). In contrast, patients belonging to group B had no
      elevation of sICAM-1 values in CSF (range 0.3-3.9 ng/ml, n = 5; p < 0.017) and
      showed minor cerebral damage with an intact BBB in most cases. In addition,
      overall analysis showed that sICAM-1 in CSF correlated with the extent of BBB
      damage as indicated by the QA (r = 0.76; p < 0.001). These results suggest that
      increased sICAM-1 levels in CSF might depict ongoing immunologic activation and
      that sICAM-1 correlates with the extent of tissue and BBB damage. The origin of
      soluble ICAM-1 in CSF and its pathophysiologic role after TBI remains to be
      clarified.

PMID- 9624626
TI  - Patterns of heat-shock protein 70 biosynthesis following human traumatic brain
      injury.
AB  - Heat-shock protein 70 (hsp70) is activated upon cellular stress/injury and
      participates in the folding and intracellular transport of damaged proteins. The
      expression of hsp70 following CNS trauma has been speculated to be part of a
      cellular response which is involved in the repair of damaged proteins. In this
      study, we measured hsp70 mRNA and protein levels within human cerebral cortex
      subjected to traumatic brain injury. Specimens were obtained during routine
      neurosurgery for trauma and processed for Northern mRNA and Western protein
      analysis. The largest increase in hsp70 mRNA levels was detected in trauma tissue
      obtained 4-6 h following injury. By 24 h, hsp70 mRNA levels were similar to
      nontrauma comparison tissues. hsp70 protein expression exhibited its greatest
      increases at 12-20 h post-injury. Immunocytological techniques revealed hsp70
      protein expression in cells with neuronal-like morphology at 12 h after injury.
      These results suggest a role for hsp70 in human cortex following TBI. Moreover,
      since the temporal induction pattern of hsp70 biosynthesis is similar to that
      reported in the rodent, our observations validate the importance of rodent brain
      injury models in providing useful information directly applicable to human brain
      injury.

PMID- 9624627
TI  - Heat-shock protein 72 expression in excitotoxic versus penetrating injuries of
      the rodent cerebral cortex.
AB  - The induction of heat shock protein 72 (hsp72) has been described in various
      experimental models of brain injury. The present study examined hsp72 expression
      patterns within the rodent cerebral cortex in experimental paradigms designed to
      mimic two mechanisms of damage produced by penetration of the cerebral cortex:
      (1) tissue tearing from the missile track and (2) diffuse excitotoxicity during
      temporary cavitation and shock wave formation. Adult male Spaque-Dawley rats
      received controlled penetration (stab) or injection of the NMDA receptor
      excitotoxin, quinolinic acid (QA), into the frontal cortex and were killed 1-24 h
      later. Tissue from the lesioned, sham-operated, or contralateral uninjected
      cortex was processed for Western and immunocytochemical analyses of hsp72 protein
      expression. By 12 h, both controlled penetration and excitotoxic brain injuries
      produced significant increases in hsp72 immunoreactivity, which decreased toward
      control levels at 24 h. However, the severity and regional distribution of hsp72
      expression varied between the two models. Specifically, the controlled
      penetration injury produced many hsp72-expressing cells near the needle track,
      while immunoreactive cells within the QA-injected cortex were found in the
      periphery of the lesion site. Morphological assessment of brain sections
      subjected to dual-labeling procedures demonstrated that cells expressing hsp72
      were primarily neuronal in both models of injury. These results suggest that
      although controlled penetration and diffuse excitotoxicity may induce similar
      temporal and cellular patterns of hsp72 expression, the spatial location of hsp72
      immunoreactive cells may differ between the two models.

PMID- 9624628
TI  - The 21-aminosteroid U-74389G reduces cerebral superoxide anion concentration
      following fluid percussion injury of the brain.
AB  - We examined the effects of the 21-aminosteroid antioxidant U-74389G (16-desmethyl
      tirilazad) on the concentration of extracellular superoxide anion following fluid
      percussion traumatic brain injury (TBI) measured by a cytochrome c-coated
      electrode and on local cerebral perfusion (CBFld) measured by laser Doppler
      flowmetry (LDF). U-74389G in a dose of 3 mg/kg reduced superoxide anion
      concentrations 60 min after TBI significantly but had no significant effect on
      CBFld. These results indicate that reduction of CBF after TBI can be dissociated
      from superoxide anion production. Persistent ischemia may limit neuroprotection
      efficacy and may contribute to divergent outcome results in clinical and animal
      trials using agents to modify reactive oxygen species.

PMID- 9624629
TI  - Axonal injury caused by focal cerebral ischemia in the rat.
AB  - The susceptibility of axons to blunt head injury is well established. However,
      axonal injury following cerebral ischemia has attracted less attention than
      damage in gray matter. We have employed immunocytochemical methods to assess the
      vulnerability of axons to cerebral ischemia in vivo. Immunocytochemistry was
      performed using antibodies to a synaptosomal-associated protein of 25 kDa
      (SNAP25), which is transported by fast anterograde transport; the 68-kDa
      neurofilament subunit (NF68kD); and microtubule-associated protein 5 (MAP5) on
      sections from rats subjected to 30 min and 1, 2, and 4 h of ischemia induced by
      permanent middle cerebral artery (MCA) occlusion. After 4 h of occlusion, there
      was increased SNAP25 immunoreactivity, which was bulbous in appearance,
      reminiscent of the axonal swellings that occur following blunt head injury.
      Increased SNAP25 immunoreactivity was present in circumscribed zones in the
      subcortical white matter and in the axonal tracts at the border of infarction, a
      pattern similar to that previously described for amyloid precursor protein.
      Although less marked, similar changes in immunoreactivity in axons were evident
      following 2 h of ischemia. MAP5 and NF68kD had striking changes in
      immunoreactivity in axonal tracts permeating the caudate nucleus within the MCA
      territory at 4 h. The appearance was roughened and disorganized compared with the
      smooth regular staining in axons within the nonischemic areas. Profiles
      reminiscent of axonal bulbs were evident in MAP5-stained sections. The changes
      seen with NF68kD and MAP5 were also evident at 2 h but were more subtle at 1 h.
      There were no changes in axonal immunoreactivity with SNAP25 or NF68kD at 30 min
      after MCA occlusion. Altered immunoreactivity following ischemia using SNAP25,
      MAP5, and NF68kD provides further evidence for the progressive breakdown of the
      axonal cytoskeleton following an ischemic insult. NF68kD and MAP5 appear to be
      sensitive markers of the structural disruption of the cytoskeleton, which
      precedes the subsequent accumulation of SNAP25 within the damaged axons. Axonal
      cytoskeletal breakdown and disruption of fast axonal transport, which are well
      recognized features of traumatic brain injury, are also sequalae of an ischemic
      insult.

PMID- 9624630
TI  - External anal sphincter hyperreflexia following spinal transection in the rat.
AB  - In the present study, long-term and short-term rat preparations were used to
      develop a model for investigating external anal sphincter (EAS) reflexes in
      intact and spinal cord-injured (SCI) rats. In this model, EAS distension with an
      external probe elicits reflex contractions of the EAS in intact, unanesthetized
      animals. At 2 h after spinal cord transection, none of the lesioned animals
      displayed EAS EMG activity. In fact, once distended, the EAS was incapable of
      maintaining closure of the anal orifice. Over a period of 4 days, spinalized
      animals developed a hyperreflexia of the EAS response. By 48 h, the rectified,
      integrated EAS EMG was significantly elevated in comparison with nonlesioned
      controls (EAS hyperreflexia). In addition, the duration of the EAS EMG bursts in
      response to sphincter distension had significantly increased. At 6 weeks after
      injury, the EAS was significantly hyperreflexic as measured by EMG burst duration
      and burst area. As with intact animals, posttransection EAS reflexes were highly
      anesthesia sensitive. These studies indicate that (1) brief distension of the
      anal orifice is sufficient to evoke a physiologically relevant reflexive
      activation of the EAS in the rat, (2) the 2- to 24-h postinjury areflexia
      observed in these experiments may be a suitable model for the study of spinal
      shock, and (3) the observed EAS hyperreflexia after chronic SCI may represent the
      permanent effects of removing descending inhibitory circuits and segmental
      plasticity, making this reflex an appropriate measure of defecatory dysfunction
      after spinal cord injury.

PMID- 9624631
TI  - Stress fracture in the world class athlete: a case study.
AB  - Stress fracture presents a difficult problem in the high performance, world-class
      athlete. Competitive demands provide little tolerance for, or agreement with,
      prolonged periods of rest which are the first line of conservative treatment
      methods. The use of a specifically programmed, pulsed, low-intensity ultrasound
      device to shorten the time of healing was investigated in a well-known gymnast
      with an Olympic deadline. Prior animal, in vitro, and clinical studies had
      established the safety and effectiveness of this device in fractures. The
      location of the stress injury was in the mid-tibia which is considered to present
      the greatest challenge to an early healing result. The low-intensity ultrasound
      device was prescribed for daily use at home. At 3 wk after the start of low
      intensity ultrasound, the stress fracture responded well and the patient was
      allowed use of tumble track, trampoline, and to do some weight-bearing
      activities, such as jumping in the pool and loading-type activities. At 4.5 wk,
      the patient progressed to full workout activities and participated in a trial
      meet for the Olympics. At 6 wk, the patient's participation in the women's
      gymnastic team event was a factor in the United States receiving a gold medal.

PMID- 9624632
TI  - Biochemistry and biomechanics of healing tendon: Part I. Effects of rigid plaster
      casts and functional casts.
AB  - PURPOSE: Traditional treatment of surgically repaired Achilles tendons includes
      complete immobilization of the joint in rigid casts for 6 to 8 wk. We tested the
      use of functional polyurethane casts as an alternative to rigid plaster casts
      after experimental tenotomy and repair of the rabbit Achilles tendon. METHODS:
      After repair the limbs of 15 experimental rabbits were immobilized in a
      functional polyurethane cast for 15 d, while those of 14 controls were
      immobilized in traditional rigid plaster casts for the same period. RESULTS:
      Functional casting resulted in a 60% increase in total collagen in the neotendon
      compared with that in rigid casting (P < 0.05). Mature collagen cross-links
      declined 8% in the tendons with functional casts. The biomechanical parameters of
      the tendons changed with functional casting, showing a 20% increase in maximum
      load and 21% increase in maximum stress. CONCLUSIONS: These changes were noted
      without any cases of tendon re-rupture in either type of cast. Thus, functional
      casting following surgery of Achilles tendons appears to improve healing without
      significant risks of re-rupture.

PMID- 9624634
TI  - Chronic ankle pain and fibrosis successfully treated with a new noninvasive
      augmented soft tissue mobilization technique (ASTM): a case report.
AB  - This clinical case report demonstrates the clinical effectiveness of a new form
      of soft tissue mobilization in the treatment of excessive connective tissue
      fibrosis (scar tissue) around an athlete's injured ankle. The scar tissue was
      causing the athlete to have pain with activity, pain on palpation of the ankle,
      decreased range of motion, and loss of function. Surgery and several months of
      conventional physical therapy failed to alleviate the athlete's symptoms. As a
      final resort, augmented soft tissue mobilization (ASTM) was administered. ASTM is
      an alternative nonsurgical treatment modality that is being researched at
      Performance Dynamics (Muncip, IN). ASTM is a process that uses ergonomically
      designed instruments that assist therapists in the rapid localization and
      effective treatment of areas exhibiting excessive soft tissue fibrosis. This is
      followed by a stretching and strengthening program. Upon the completion of 6 wk
      of ASTM therapy, the athlete had no pain and had regained full range of motion
      and function. This case report is an example of how a noninvasive augmented form
      of soft tissue mobilization (ASTM) demonstrated impressive clinical results in
      treating a condition caused by connective tissue fibrosis.

PMID- 9624633
TI  - Biochemistry and biomechanics of healing tendon: Part II. Effects of combined
      laser therapy and electrical stimulation.
AB  - PURPOSE: In previous studies we demonstrated that early mechanical loading and
      laser photo-stimulation independently promoted tendon healing. Thus, we tested
      the hypothesis that a combination of laser phototherapy and mechanical load would
      further accelerate healing of experimentally tenotomized and repaired rabbit
      Achilles tendons. METHODS: Following surgical tenotomy and repair, the tendons of
      experimental and control rabbits were immobilized in polyurethane casts for 5 d.
      The repaired tendons of experimental rabbits received mechanical load via
      electrical stimulation-induced contraction of the triceps surae for 5 d. In
      addition, experimental tendons were treated with daily doses of 1 J.cm-2 low
      intensity helium-neon laser throughout the 14-d experimental period. RESULTS: The
      combination of laser photostimulation and mechanical load increased the maximal
      stress, maximal strain, and Young's modulus of elasticity of the tendons 30, 13,
      and 33%, respectively. However, MANOVA revealed no statistically significant
      differences in these biomechanical indices of repair of control and experimental
      tendons. Biochemical assays showed a 32% increase in collagen levels (P < 0.05)
      and an 11% decrease in mature cross-links in experimental tendons compared with
      that in controls (P > 0.05). Electron microscopy and computer morphometry
      revealed no significant differences in the morphometry of the collagen fibers and
      no visible differences in the ultrastructure of cellular and matrical components
      of control and experimental tendons. CONCLUSIONS: These findings indicate that
      the combination of laser photostimulation and early mechanical loading of tendons
      increased collagen production, with marginal biomechanical effects on repaired
      tendons.

PMID- 9624635
TI  - The effect of exercise on leptin concentration in healthy men and in type 1
      diabetic patients.
AB  - PURPOSE: Leptin is a recently discovered hormone that appears as a regulator of
      energy balance. It is important to know whether leptin concentrations are changed
      under conditions of altered energy homeostasis. Consequently, we examined the
      effects of exercise with fasting and exercise with feeding on circulating leptin
      concentrations in healthy men and in type 1 diabetic patients with normal body
      weight and well controlled diabetes. METHODS: Leptin concentrations were
      determined with radioimmunoassay. RESULTS: During a 3-h cycle ergometer exercise
      with fasting, leptin decreased by 42% (P < 0.01) in nine healthy men and by 23%
      (P = 0.05) in eight male type 1 diabetic patients. Leptin fell equally by 12% (P
      < 0.03) both in nine healthy men and in eight male type 1 diabetic patients who
      were studied as a resting control group. The absolute fall in leptin in healthy
      men was similar in the exercise and resting control groups (0.8 +/- 0.1
      microgram.L-1 vs 0.8 +/- 0.2 microgram.L-1). However, due to lower leptin
      concentration before the exercise, the relative decrease (42%) was greater than
      during the resting control study (12%, P < 0.005). This difference was not seen
      in the diabetic patients. Fasting leptin concentration correlated positively with
      BMI (r = 0.75, P < 0.001) and fasting insulin (r = 0.71, P < 0.01) in healthy men
      as well as with insulin level (r = 0.54, p < 0.05) in type 1 diabetic patients.
      When exercise was performed with feeding, and this was associated with a
      significant rise in serum cortisol level (marathon run, 14 healthy men and 7 type
      1 diabetic patients), leptin concentration did not change significantly.
      CONCLUSIONS: 1) During morning hours, leptin decreases both in healthy men and in
      type 1 diabetic patients, reflecting a diurnal variation of leptin concentration
      and the effect of fasting on leptin concentration. 2) The fall in leptin during
      morning hours is augmented by physical exercise in healthy men. 3) If exercise is
      performed with feeding and associated with a rise in serum cortisol level, leptin
      concentration remains unchanged. These data suggest that although exercise may
      reduce circulating leptin levels, the effect is small and can be counterbalanced
      by feeding or a rise in serum cortisol concentration.

PMID- 9624636
TI  - Exercise as a mediator of psychological and nutritional effects of testosterone
      therapy in HIV+ men.
AB  - PURPOSE: The purpose of this study was to determine whether exercise mediates the
      psychological and nutritional effects of testosterone therapy in men with
      symptomatic HIV illness, low serum testosterone, and clinical symptoms of
      hypogonadism. METHODS: A 12-wk open trial of biweekly intramuscular testosterone
      injections was conducted, with 54 men completing the trial and exercise
      assessments. Most (71%) men were diagnosed with AIDS; 41% had a CD4 < 50. One
      third of the men were diagnosed with major depression, and nearly half had some
      evidence of wasting. Twenty-nine men (54%) engaged in exercise (predominantly
      resistance training) during the trial. Exercisers did not differ from
      nonexercisers on any measure of psychological well being or nutritional status at
      baseline. RESULTS: After 12 wk of testosterone treatment, those who exercised
      showed significant improvement in mood (Hamilton Rating Scale for Depression; HAM
      D) and overall distress (Brief Symptom Inventory; BSI) (P < 0.000 for both), as
      well as a significant increase in body cell mass (P < 0.01) and lean body mass
      (mean increase of 2.6 kg; P < 0.000) as measured by bioelectric impedance
      analysis. In contrast, nonexercisers showed improvement on the HAM-D (P < 0.000),
      but not the BSI or measures of nutritional status. CONCLUSION: These findings
      indicate that exercise may be an important adjunct to testosterone therapy in the
      treatment of psychological distress and wasting symptoms in men with symptomatic
      HIV illness.

PMID- 9624637
TI  - Blood pressure lowering effect of low intensity aerobic training in elderly
      hypertensive patients.
AB  - PURPOSE: The purpose of this investigation was to determine the effect of 9
      months of low intensity aerobic training on blood pressure in elderly
      hypertensive patients who were receiving antihypertensive medication. METHODS:
      The training group (N = 13; mean age 75.4 +/- 5.4 yr) agreed to take part in
      physical training using a treadmill with an exercise intensity at the blood
      lactate threshold (LT) for 30 min three to six times a week for 9 months. The
      rest (N = 13; mean age 73.1 +/- 4.2 yr) served as controls. RESULTS: The resting
      systolic (-15 +/- 8 mm Hg), mean (-11 +/- 6 mm Hg), and diastolic blood pressures
      (-9 +/- 9 mm Hg) decreased significantly after 3 months of training and the blood
      pressure of all participants stabilized at a significantly lower level by the end
      of the study (9 months) in the training group, whereas no significant changes in
      blood pressure were found in the control group. Both the pretraining systolic and
      diastolic blood pressure of those recruited patients negatively correlated with
      those changes after the training (SBP: P < 0.01; DBP: P < 0.05, respectively).
      After 1 month of detraining in five patients, the blood pressure levels were
      similar to those in the pretraining state. The LT increased significantly in the
      training group (P < 0.01). CONCLUSION: In conclusion, an additional
      antihypertensive effect of mild aerobic training at the LT was confirmed in
      elderly patients receiving antihypertensive medication. The cessation of such
      training in five patients, however, resulted in a relatively rapid return to
      pretraining levels within a month.

PMID- 9624638
TI  - The impact of scalar variable and process on athlete-control comparisons of
      cardiac dimensions.
AB  - PURPOSE: This study compared linear left ventricular dimensions and mass (LVM),
      before and after normalizing for body dimensions via allometric and ratio
      standard scaling. METHODS: Height (HT; m), body mass (BM; kg), body surface area
      (BSA; m2), and fat-free mass (FFM; kg) were measured in elite male weight lifters
      (N = 11) and age-matched controls (N = 45). Septum (ST), posterior wall (PWT),
      and internal dimension in diastole (LVIDd) were measured from M-mode
      echocardiographic traces and used to calculate LVM. Via multivariate allometric
      scaling, common group power function exponents were identified for all cardiac
      dimensions related to all body size scalars. t-tests were used to compare group
      differences in absolute and scaled data. RESULTS: BM, FFM, and BSA, as well as
      absolute LVM (262 +/- 54 vs 206 +/- 39) and ST (11 +/- 1 vs 9 +/- 1), were
      greater in the athletes (P < 0.05). All exponents conformed to dimensionality
      theory within 95% confidence limits. Fat-free mass presented the highest multiple
      R value and the least residual sum of squares of any scalar variable. If FFM was
      used to scale, no difference in LVM remained (P > 0.05). CONCLUSIONS: Data
      suggest that any group effect on cardiac dimensions is substantially altered by
      the scaling procedure. The choice of the most appropriate variable and process
      for partitioning out any effect of body dimensions on cardiac dimensions in
      similar studies requires attention.

PMID- 9624639
TI  - Self-selected recreational exercise has no impact on early postpartum lactation
      induced bone loss.
AB  - Although exercise is known to positively impact bone mineral density (BMD), its
      effect on lactation-induced BMD loss has not been previously evaluated in a case
      control study. PURPOSE: The purpose of this study was to compare lactation
      induced bone changes in women who engaged in regular, self-selected, recreational
      exercise versus those who refrained from such during early postpartum. METHODS:
      Subjects were 20 healthy, lactating women who either exercised regularly
      (exercise, E; N = 11) or refrained from such (control, C; N = 9) during the first
      3 months postpartum. Although preconception VO2max was significantly higher in E
      than C (E = 54.1, C = 36.9 mL.min-1.kg-1), no significant group differences were
      observed for parity, age, height, weight (WT), % body fat, dietary calcium
      intake, lactation calcium loss, and serum estradiol. Total body (TB), lumbar
      spine (LS), and femur neck (FN) BMD were measured within 2 wk of parturition and
      repeated at 3 months postpartum by dual energy x-ray absorptiometry. RESULTS:
      Although TB was unchanged, BMD decreased significantly from baseline in both
      groups at LS (C = -5.4, E = -4.1%) and FN (C = -2.7, E = -2.8%). WT decreased
      significantly over time but was not significantly correlated with BMD loss. No
      significant group by time interactions were observed for WT or BMD changes.
      CONCLUSION: These results suggest that regular, self-selected, recreational E has
      no impact on early postpartum lactation-induced BMD loss.

PMID- 9624641
TI  - Pre-exercise carbohydrate ingestion: effect of the glycemic index on endurance
      exercise performance.
AB  - PURPOSE: This study aimed to examine the effect of glycemic index of pre-exercise
      carbohydrate (CHO) ingestion on exercise metabolism and performance. METHODS:
      Eight endurance trained men ingested a high glycemic index (HGI), low glycemic
      index (LGI), or a placebo (CON) meal 45 min before exercise and then cycled for
      50 min at 67% VO2max. Subjects subsequently performed a 15-min self-paced
      performance ride in which total work (kJ) was recorded. RESULTS: Plasma glucose
      concentrations were higher (P < 0.01) after ingestion in HGI compared with LGI
      and CON (7.53 +/- 0.64 vs 5.55 +/- 0.21 and 4.65 +/- 0.14 mmol.L-1 for HGI, LGI,
      and CON, respectively, 30 min postprandial; mean +/- SE) but declined at the
      onset of exercise and were lower (P < 0.01) compared with LGI and CON (4.03 +/-
      0.31 vs 4.64 +/- 0.24 and 5.09 +/- 0.16 mmol.L-1 for HGI, LGI, and CON
      respectively; mean +/- SE) at 10 min of exercise. Plasma glucose remained
      depressed (P < 0.01) until 30 min into exercise in HGI compared with other
      trials. Plasma insulin concentrations were higher (P < 0.01) following ingestion
      during rest and exercise in HGI compared with LGI and CON. Plasma FFA
      concentrations were lower (P < 0.05) following ingestion in HGI and LGI compared
      with CON and higher (P < 0.05) in LGI compared with HGI at the start and end of
      exercise. RER and CHO oxidation was higher (P < 0.01) in HGI compared with LGI
      and CON during submaximal exercise. There were no differences in work output
      during the performance cycle. CONCLUSIONS: These data indicate that pre-exercise
      CHO feedings with varying glycemic indexes do not affect exercise performance
      following short term submaximal exercise despite alterations in metabolism.

PMID- 9624640
TI  - Effect of pyruvate and dihydroxyacetone on metabolism and aerobic endurance
      capacity.
AB  - Pyruvate and dihydroxyacetone are three carbon compounds that when infused
      directly into the blood or taken orally produce strong metabolic effects. When
      chronically fed to animals as part of their diet, pyruvate plus dihydroxyacetone
      reduce the rate of weight gain and body fat content during growth. These
      alterations in growth pattern appear to be the result of an increased loss of
      calories as heat at the expense of storage of lipid. Pyruvate-dihydroxyacetone
      supplementation has also been found to improve the insulin sensitivity of insulin
      resistant rats and reduce plasma cholesterol levels induced by a high cholesterol
      diet as well as lower blood pressure and heart rate in obese individuals. When
      infused in rats during prolonged treadmill running, pyruvate reduced run time to
      exhaustion by approximately 67%. However, when provided as an oral supplement for
      several days, it has enhanced aerobic endurance capacity. The mechanism of action
      is unclear, but available data suggest that the increase in performance following
      pyruvate-dihydroxyacetone supplementation may be a result of an increased
      reliance on blood glucose, thus sparing muscle glycogen. In summary, chronic
      supplementation of pyruvate-dihydroxyacetone may be beneficial from a preventive
      medicine prospective as well as for certain athletic endeavors.

PMID- 9624642
TI  - Effects of intermittent ischemia on contractile properties and myosin isoforms of
      skeletal muscle.
AB  - PURPOSE: This study determined the effects of intermittent ischemia on the
      contractile properties, fatigue (Tf), and myosin heavy chain composition (MHC) in
      the rat gastrocnemius-plantarissoleus muscle (GPS) complex. METHODS: Fifty rats
      were divided into four groups: control (C, N = 12), severed (femoral artery) (S,
      N = 12), exercise (E, N = 13), and severed/exercise (SE, N = 13). Ischemia was
      elicited only in the SE group by daily exercise and the other groups served as
      controls. Exercise in the E and SE groups consisted of running on a treadmill
      approximately 35 min.d-1, 5 d.wk-1 for 7 wk. RESULTS: Body weight, muscle weight,
      and absolute force were less in the SE group compared with those in C (12, 18,
      and 12% respectively). However, relative force (N.g-1 of muscle) was greater in
      the SE group compared with that in C (8%). Maximal shortening velocity (Vmax) was
      lower in the SE group compared with that in all others (10-14%). Tf was less in
      the S group compared with that in C and E (28 and 30%, respectively). Type IIx
      MHC increased and type IIb decreased in gastrocnemius and plantaris muscles in SE
      compared with those in C. CONCLUSIONS: These data indicate that intermittent
      ischemia caused a decrease in muscle mass, maximal force development, and Vmax,
      but had no effect on Tf. The decrease in Vmax may have been related to myosin
      alterations in the muscles.

PMID- 9624643
TI  - Effect of glutamine supplementation on changes in the immune system induced by
      repeated exercise.
AB  - The ability of lymphocytes to proliferate and generate lymphokine activated
      killer (LAK) cell activity in vitro is dependent on glutamine. In relation to
      intense exercise the lymphocyte concentration, the proliferative response, the
      natural killer and LAK cell activity, and the plasma glutamine concentration
      decline. It has been hypothesized that in relation to physical activity a lack of
      glutamine may temporarily affect the function of the immune system. PURPOSE: The
      purpose of this study was to examine the influence of glutamine supplementation
      on exercise-induced immune changes. METHODS: In a randomized cross-over placebo
      controlled study, eight healthy male subjects performed three bouts of ergometer
      bicycle exercise lasting 60, 45, and 30 min at 75% of their VO2max separated by 2
      h of rest. RESULTS: The arterial plasma glutamine concentration declined from 508
      +/- 35 (pre-exercise) to 402 +/- 38 microM (2 h after the last exercise bout) in
      the placebo trial and was maintained above pre-exercise levels in the glutamine
      supplementation trial. The numbers of circulating lymphocytes and the
      phytohemagglutinin-stimulated lymphocyte proliferative response declined 2 h
      after, respectively, during each bout of exercise, whereas the LAK cell activity
      declined 2 h after the third bout. Glutamine supplementation in vivo, given in
      the described doses at the specific times, did not influence these changes.
      CONCLUSION: The present study does not appear to support the hypothesis that
      those aspects of postexercise immune changes studied are caused by decreased
      plasma glutamine concentrations.

PMID- 9624644
TI  - Immune system activation and fatigue during treadmill running: role of
      interferon.
AB  - Extreme fatigue often accompanies infection and other diseases, but the causal
      mechanisms are unknown. Recent research has focused on various cytokines as
      potential immune system mediators of fatigue during illness. Interferon
      alpha/beta (IFN-alpha/beta) has attracted the most interest in this regard.
      PURPOSE: The purpose of this research was to study the effect of IFN-alpha/beta
      on fatigue during treadmill running in mice. METHODS: Mice (male CD-1) were
      acclimated to treadmill running for 4 d before experimental sessions. In
      experiment 1 (EXP 1), mice were injected with either polyI:C (pI:C) (5 mg.kg-1
      body weight) or saline (CON) 12 or 24 h before the exercise session. These
      sessions consisted of treadmill running to fatigue (approximately 3 h, 19-24
      m.min-1, 5% grade, no shock). In experiment 2 (EXP 2), mice were injected 24 h
      before exercise with normal rabbit serum (CON), pI:C, or pI:C + anti-IFN
      alpha/beta antibody (pI:C + Ab). RESULTS: The results of EXP 1 showed that the
      plasma IFN-alpha/beta titer was much higher at 24 h than at 12 h after pI:C
      injection (P < 0.001) and that run time to fatigue was significantly reduced only
      when the exercise occurred 24 h after injection (P < 0.05). In EXP 2,
      administration of the anti-IFN-alpha/beta antibody attenuated both the pI:C
      induced increase in plasma IFN-alpha/beta (P < 0.001) and the decrease in run
      time to fatigue (r = -0.81, P < 0.001). CONCLUSIONS: These results suggest that
      immune system activation by pI:C was associated with early fatigue during
      prolonged treadmill exercise and that this effect may, at least partially, result
      from increased IFN-alpha/beta.

PMID- 9624645
TI  - Multiple variables explain the variability in the decrement in VO2max during
      acute hypobaric hypoxia.
AB  - PURPOSE: We used multiple regression analyses to determine the relationships
      between the decrement in sea level (SL, 760 Torr) VO2max during hypobaric hypoxia
      (HH) and variables that could alter or be related to the decrement in VO2max.
      METHODS: HH conditions consisted of 682 Torr, 632 Torr, and 566 Torr, and the
      measured independent variables were SL-VO2max, SL lactate threshold (SL-LT), the
      change in hemoglobin saturation at VO2max between 760 and 566 Torr (delta
      SaO2max), lean body mass (LBM), and gender. Male (N = 14) and female (N = 14)
      subjects of varied fitness, training status, and residential altitude (1,640
      2,460 m) completed cycle ergometry tests of VO2max at each HH condition under
      randomized and single-blinded conditions. RESULTS: VO2max decreased significantly
      from 760 Torr after 682 Torr (approximately 915 m) (3.5 +/- 0.9 to 3.4 +/- 0.8
      L.min-1, P = 0.0003). Across all HH conditions, the slope of the relative
      decrement in VO2max (%VO2max) during HH was -9.2%/100 mm Hg (-8.1%/1000 m) with
      an initial decrease from 100% estimated to occur below 705 Torr (610 m). Step
      wise multiple regression revealed that SL-VO2max, SL-LT, delta SaO2max, LBM, and
      gender each significantly combined to account for 89.03% of the variance in the
      decrement in VO2max (760-566 Torr) (P < 0.001). CONCLUSIONS: Individuals who have
      a combination of a large SL-VO2max, a small SL-LT (VO2, L.min-1), greater
      reductions in delta SaO2max, a large LBM, and are male have the greatest
      decrement in VO2max during HH. The unique variance explanation afforded by SL-LT,
      LBM, and gender suggests that issues pertaining to oxygen diffusion within
      skeletal muscle may add to the explanation of between subjects variability in the
      decrement in VO2max during HH.

PMID- 9624646
TI  - Metabolic and endocrine responses to cold air in women differing in aerobic
      capacity.
AB  - PURPOSE: The purpose of this study was to measure resting metabolic rate, plasma
      norepinephrine, and plasma immunoreactive beta endorphin during exposures to cold
      air during two consecutive 5-d periods, separated by 2 weekend days, in two
      groups of women differing in aerobic fitness. METHODS: Plasma norepinephrine
      (NE), plasma immunoreactive beta-endorphin (IBE), and resting metabolic response
      (RMR) were measured during repeated exposures to 3.5 degrees C air in two groups
      of women differing in aerobic fitness. Ten women, separated into highly fit (HFW)
      and less fit (LFW) groups, sat in 22 degrees C air for 45 min followed by 45 min
      in 3.5 degrees C air each day during two consecutive 5-d periods separated by two
      weekend days. RESULTS: Norepinephrine was not different between groups during
      warm air exposure; however, following 45 min of cold air, NE was two times higher
      in HFW compared with that in LFW (P < 0.001). Plasma IBE was elevated (P < 0.02)
      in HFW compared with that in LFW but was not affected by exposure to cold on any
      test day. Warm RMR was not different between groups and remained unchanged during
      the study period. Cold RMR was significantly higher in LFW compared with that in
      HFW (P < 0.01). Resting metabolic rate peaked at 30% of VO2peak in LFW by the 5th
      minute of cold exposure on day 1 before declining to 21% and remaining steady. In
      contrast, RMR in HFW peaked at about 13% and then fell to 9.4% before slowly
      increasing to 14% by the end of 45 min. On other test days HFW RMR increased to
      14% of VO2peak and rose slowly through 45 min of cold exposure while LFW RMR
      peaked at 24% of VO2peak before declining to 20% and remaining steady.
      CONCLUSIONS: Our findings suggest that, in women, aerobic fitness alters the
      endocrine and metabolic responses to acute cold air exposure. The norepinephrine
      response is exaggerated in highly fit women exposed to cold but not the metabolic
      response. Immunoreactive beta endorphin was not affected by exposure to cold but
      was elevated in highly fit women. We further conclude that the temperature
      threshold for acclimation to cold air by women may be higher than the air
      temperature used in this study.

PMID- 9624647
TI  - Effects of hydration changes on bioelectrical impedance in endurance trained
      individuals.
AB  - PURPOSE: The purpose of this study was to determine how differences in hydration
      states and ion content of hydrating fluids affected bioelectrical impedance (BI)
      and hydrostatic weighing (HW) measurements. METHODS: Fifteen athletic subjects
      aged 19-56 yr were recruited. Relative body fat (%), fat-weight (FW), and fat
      free weight (FFW) were assessed using BI and HW under normal conditions (N),
      hypohydration (HPO), rehydration (RHY), and superhydration (SHY) states. During
      the RHY and SHY trial periods, subjects were hydrated with either distilled water
      or an electrolyte solution (ELS). HPO and SHY levels were set at 3% of each
      person's normally hydrated body weight. RESULTS: Comparison between the distilled
      water and the ELS trials indicated that hydration solution had no effect on BI or
      HW. Thus, the results presented are the trial means of both hydration solutions
      combined. Both BI and HW were shown to be highly test-retest reliable (r-values:
      0.96 and 0.99, respectively). The effects of exercise induced HPO followed by RHY
      on body composition values indicated that HW was very stable across measurement
      periods while BI was not. From N to the HPO state, BI %BF declined from 14.4 +/-
      5.3% to 12.3 +/- 5.3%, respectively. After RHY, BIA %BF increased to 15.5 +/-
      5.8%. Similar findings occurred when subjects were superhydrated (N-BI = 13.2 +/-
      5.3%; SHY-BI = 15.4 +/- 5.6%). With a comparison of the intercepts and slopes of
      HW and BIA for the N and SHY states, it was clear hydration status significantly
      affected the intercepts (HW: 0.37 vs. BI: 1.85) and not the slopes (HW: 1.00 vs
      BI: 0.99). As a result, a majority of all fluid changes were interpreted as FW by
      BI. During HPO, 82% of the weight loss was considered FW while during RHY or SHY,
      128% and 85% of the water weight regain/gain was considered FW. CONCLUSION: These
      results indicate that BI is not a valid technique in athletes, especially when
      wanting to determine body composition effects of training/detraining. This study
      indicates that even small fluid changes such as those that occur with endurance
      training may be interpreted incorrectly as changes in an athlete's body fat
      content.

PMID- 9624649
TI  - Influences of cardiorespiratory fitness levels and other predictors on
      cardiovascular disease mortality in men.
AB  - PURPOSE: This investigation quantifies the relation between cardiorespiratory
      fitness levels and cardiovascular disease (CVD) mortality within strata of other
      CVD predictors. METHODS: Participants included 25,341 male Cooper Clinic patients
      who underwent a maximal graded exercise test. CVD death rates were determined for
      low (least fit one-fifth), moderate (next two-fifths), and high (top two-fifths)
      cardiorespiratory fitness categories by strata of smoking habit, blood
      cholesterol level, resting blood pressure, and health status. There were 226
      cardiovascular deaths during 211,996 man-years of follow-up. RESULTS: For
      individuals with none of the major CVD predictors (smoking, elevated resting
      systolic blood pressure, elevated blood cholesterol), there was a strong inverse
      relation (P = 0.001) between fitness level and CVD mortality. An inverse relation
      between CVD mortality and fitness level was seen within strata of cholesterol
      levels and health status. No evidence of a trend (P = 0.60) for decreased
      mortality was seen across fitness levels for individuals with elevated systolic
      blood pressure; however, a strong inverse gradient (P < 0.001) was seen across
      fitness levels for individuals with normal systolic blood pressure. There was a
      tendency for association between high levels of fitness and decreased CVD
      mortality in smokers compared with low and moderately fit smokers (P < 0.076).
      There was no significant association between level of fitness and CVD mortality
      for individuals with multiple (two or more) predictors (P = 0.325). Approximately
      20% of the 226 CVD deaths in the population studied were attributed to low
      fitness level. CONCLUSIONS: Moderate and high levels of cardiorespiratory fitness
      seem to provide some protection from CVD mortality, even in the presence of well
      established CVD predictors.

PMID- 9624648
TI  - Cardiorespiratory fitness and cardiovascular disease risk factors in
      postmenopausal women.
AB  - PURPOSE: The purpose of the present study was to determine if individuals with
      high levels of cardiorespiratory fitness have better levels of the cardiovascular
      disease (CVD) risk factors of total cholesterol (TC), HDL cholesterol (HDL),
      total cholesterol/HDL cholesterol ratio (TC/HDL), triglycerides (TG), and
      fibrinogen (FIB) when compared with those with low fitness, in 283 nonsmoking,
      postmenopausal women. Second, we examined the relation between fitness and CVD
      risk after controlling for use of hormones and other possible confounding
      factors. METHODS: These analyses were done on a subset of nonsmoking,
      postmenopausal women in the Aerobics Center Longitudinal Study (ACLS). Records of
      postmenopausal women who completed a preventive medicine physical examination
      between 1987 and 1995 were examined. Cardiorespiratory fitness level was
      determined by total treadmill time to exhaustion on a graded exercise test; CVD
      risk factors were assessed via blood analysis. RESULTS: On cross-sectional
      regression analysis, fitness was significantly associated (P < or = 0.005) with
      TC (r2 = 0.08), TC/HDL (r2 = 0.12), TG (r2 = 0.09), and FIB (r2 = 0.06), and an
      increase in HDL (r2 = 0.04). After controlling for hormone status, age, year of
      testing, and blood glucose, each outcome variable remained significantly
      associated with cardiorespiratory fitness (P < 0.05). TC/HDL and TG continued to
      be significantly related to cardiorespiratory fitness after adjusting for body
      mass index (BMI) as a control variable (P < 0.01). The lack of significance
      between TC, HDL, and FIB with cardiorespiratory fitness after adjusting for BMI
      is likely due to the biological relationship between cardiorespiratory fitness
      and BMI (r2 = 0.19). CONCLUSIONS: We conclude that cardiorespiratory fitness is
      an important independent determinant of blood lipid and FIB levels in nonsmoking
      postmenopausal women, with or without HRT.

PMID- 9624650
TI  - Primary dysmenorrhea and physical activity.
AB  - It has been widely claimed that exercise is beneficial to dysmenorrhea, yet solid
      evidence is lacking. Studies investigating this relationship have been reviewed
      for this paper. Most showed decreased prevalence and/or improved symptomatology
      with exercise. However, controlled longitudinal studies involving women with
      confirmed primary dysmenorrhea who are sufficiently blinded to the study
      objectives are necessary before a definite relationship between exercise and
      dysmenorrhea can be established.

PMID- 9624651
TI  - Tracking of health-related fitness components in youth ages 9 to 12.
AB  - PURPOSE: The purpose of this study was to examine the tracking of multiple health
      related fitness components in children from fourth to sixth grade. METHODS: A
      battery of fitness tests was used to measure 414 children (213 boys, 201 girls,
      mean = 9.48 yr, +/- 0.41) from three elementary schools in Southern California.
      Children were assessed during the fall and spring of each grade. Baseline scores
      were correlated (Spearman) with each subsequent time point. RESULTS: For boys 3
      yr correlations of body mass index (BMI) (0.89), skinfold thickness (0.80), sit
      and-reach test (0.67), and the pull-up test (0.66) indicated high levels of
      tracking. Mile run (0.56), sit-up test (0.46), and waist-to-hip ratio (0.30)
      tracked moderately. For girls BMI (0.83), sum of skinfolds (0.75), sit-and-reach
      test (0.72), and the pull-up test (0.63) tracked highly, while mile run (0.42),
      sit-up test (0.47), and waist-to-hip ratio (0.42) tracked moderately.
      CONCLUSIONS: Results suggest that relative rankings of BMI, skinfold thickness,
      and sit-and-reach test performance are more likely to track during early
      adolescence. Measures of cardiovascular fitness, muscular strength, and endurance
      and fat distribution may be less likely to track into adolescence, possibly
      because they are more influenced by changes in physical activity or because
      tracking may be reduced by measurement error.

PMID- 9624652
TI  - Comparison of the kinematics of the full-instep and pass kicks in soccer.
AB  - PURPOSE: The goal of this study was to gain a better understanding of the
      mechanics of the inside-of-the-foot passing shot used in soccer ("pass kick").
      METHODS: The motions of the pass kick were compared with those of the full-instep
      kick ("full kick"). The study followed an inverse dynamics approach, using three
      dimensional cinematographic techniques. RESULTS: At impact, the pelvis and the
      thigh-shank plane pointed more toward the right in the pass kick; the shank-foot
      plane also pointed further outward relative to the thigh-shank plane. Knee
      extension accounted for most of the speed of the foot in both kicks (86% in the
      full kick; 67% in the pass kick). In the pass kick, pelvis tilt toward the right
      and hip adduction contributed to a medial component of foot velocity (8.4 m.s-1)
      normal to the thigh-shank plane, which made the resultant foot velocity vector
      more oblique to the plane than in the full kick. This facilitated ball impact
      with the medial aspect of the foot. The slower ball speed in the pass kick was
      because of a slower foot speed (18.3 m.s-1 vs 21.6 m.s-1). Limitations in the
      maximum medial velocity that can be generated may force players to restrain the
      within-plane (and therefore also the resultant) velocity of the foot to be able
      to impact the ball squarely with the medial aspect of the foot. CONCLUSIONS: To
      impact the ball with the medial aspect of the foot in the pass kick, the player
      orients the pelvis, the right leg, and the foot more toward the right and
      introduces a medial component of foot velocity. However, most of the speed of the
      foot is still generated through knee extension.

PMID- 9624653
TI  - The role of mechanical and neural restraints to joint range of motion during
      passive stretch.
AB  - Musculoskeletal flexibility is typically characterized by maximum range of motion
      (ROM) in a joint or series of joints. Resistance to passive stretch in the mid
      range of motion is a function of the passive mechanical restraints to motion.
      However, an active contractile response may contribute resistance at terminal
      ROM. PURPOSE: The purpose of this study was to examine whether maximum straight
      leg raise (SLR) ROM was limited by passive mechanical forces or stretch-induced
      contractile responses to stretch. METHODS: An instrumented SLR stretch was
      applied to the right leg of 16 subjects ending at the point of discomfort. Torque
      was measured with a load cell attached to the ankle. An electrogoniometer was
      placed on the hip, and the knee was braced in extension. Surface electrodes were
      placed over the rectus and biceps femoris muscles. Following the instrumented SLR
      test, maximum ROM was measured goniometrically by a physical therapist using the
      standard SLR test (PT SLR ROM). Torque/ROM curves were plotted for each subject.
      RESULTS: PT SLR ROM was positively related to total energy absorbed (area under
      the curve) (r = 0.49, P = 0.044), negatively related to the increase in torque
      from 20 to 50 degrees (r = -0.81, P < 0.0001) and negatively related to energy
      absorbed from 20 to 50 degrees (r = -0.73, P < 0.001). Minimal stretch-induced
      hamstring activity was elicited (3 +/- 1% MVC), and the EMG activity was
      unrelated to PT SLR ROM (r = -0.06, P = 0.8). A combination of the increase in
      torque from 20 to 50 degrees and total energy absorbed improved the relationship
      to PT SLR ROM (r = 0.89, P = 0.001). Seventy-nine percent of the variability in
      maximum SLR ROM could be explained by the passive mechanical response to stretch.
      CONCLUSIONS: These data lend support to the concept that musculoskeletal
      flexibility can be explained in mechanical terms rather than by neural theories.

PMID- 9624654
TI  - Postexercise potentiation of the H-reflex in humans.
AB  - Post-muscle activation effects on segmental reflexes reveal divergent results
      dependent upon the manner in which the muscle is activated. Electrically
      activating triceps surae invokes a potentiation of the Achilles' tendon reflex
      and the soleus (S) H-reflex termed posttetanic potentiation. In contrast, brief
      volitional activation produces a subsequent potentiation of tendon reflexes,
      whereas H-reflexes become depressed. PURPOSE: The present investigation explored
      the effect of an intense bout of volitional resistance exercise on the S and
      lateral gastrocnemius (LG) H-reflexes to determine if a potentiation of the H
      reflex could be induced with physiological stimuli. METHODS: LG and S H-reflexes
      were obtained from 10 college age men and women before and after a vigorous bout
      (eight sets of 10 repetitions) of concentric-eccentric triceps surae exercise.
      RESULTS: Every subject displayed an initial depression of the LG (P < 0.01) and S
      H-reflex (P < 0.05) immediately postexercise, consistent with postactivation
      depression. As a group, there was a significant (P > 0.01) potentiation of the LG
      H/M ratio following the depression. Five of 10 subjects demonstrated this
      potentiation, which often lasted 10 min postexercise. The other five subjects
      displayed a longer and more profound early depression followed by a return to
      control levels. CONCLUSION: The data suggest that at least two overlapping
      processes are occurring, a brief depression followed by or superimposed over a
      longer lasting potentiation. Possible neural mechanisms and implications to
      strength training are discussed.

PMID- 9624655
TI  - Perceived exertion and the preferred cycling cadence.
AB  - PURPOSE: To determine whether an association exists between peripheral comfort
      level, as reflected by differentiated RPE measures, and the preferred cadences of
      subjects who differed in cycling experience and fitness level. METHODS: Twelve
      experienced cyclists (C), ten runners (R), and ten less-trained noncyclists (LT),
      all of whom were male, pedaled at three power outputs (C, R: 100, 150, 200 W; LT:
      75, 100, 150 W) and six cadences (50, 65, 80, 95, 110 rpm, and their freely
      chosen cadence) for 5 min per condition. Differentiated ratings of perceived
      exertion (RPE) were recorded during the fifth minute of the exercise. It was
      hypothesized that the preferred cadence selected by C, R, and LT would be the
      same as the cadence at which the peripheral RPE was minimized. Comparison of
      means failed to support this hypothesis. RESULTS: Irrespective of rating scale
      (peripheral, central, overall), the cadences at which RPE was minimized were
      lower than the preferred cadences, except for LT at 150 W, where there was no
      significant difference between the preferred cadence and the cadences at which
      the peripheral and overall RPE were minimized. C tended toward a more curvilinear
      RPE-cadence relationship compared with R and LT. Mean data for all groups showed
      that only the peripheral RPE decreased from 50 to 65 rpm, whereas peripheral,
      overall, and central RPE remained essentially unchanged from 65 to 80 rpm but
      increased from 80 to 110 rpm. There was a trend for the cadences at which RPE was
      minimized for C to be higher than the cadences that minimized RPE in either R or
      LT. For all groups, the cadences at which peripheral RPE was minimized were
      significantly higher than the cadences at which either the overall or central
      ratings were minimized. CONCLUSION: The small magnitudes of change in the RPE
      score across cadence, particularly in C and R, suggest that RPE may not be a
      critical variable in cadence selection during submaximal power output cycling.

PMID- 9624656
TI  - Acute weight gain and its relationship to success in high school wrestlers.
AB  - OBJECTIVE: The purpose of this study was to investigate 1. the extent of weight
      gain by high school wrestlers between an evening weigh-in and the first round of
      wrestling the next morning and 2. the relationship between weight gain and
      wrestling success. METHODS: Body weights of competitors (N = 260) in a high
      school wrestling tournament were recorded at official weigh-in and again, about
      12 h later, immediately before the first round of wrestling. Data for the
      heavyweight class was excluded. Weight gain (WG in kg), relative weight gain (RWG
      in %), and weight discrepancy between opponents (WD in kg) were calculated from
      data obtained at the weighings. The mean WG for all wrestlers was 1.3 kg +/- 1.1
      with a range of -2.0 kg to +4.4 kg. This corresponds to RWG of 2.2 +/- 1.7% body
      weight. RESULTS: WG in the lower weight classes was statistically larger than
      that seen in the highest weight classes (P < 0.05). The smallest RWG was seen in
      the 189-lb. class (1.1 +/- 1.9%), and the largest RWG was seen in the 112-lb.
      class (3.0 +/- 2.1%). Average WD between competitors was 1.7 +/- 1.5 kg (range 0
      7.5 kg.). Average WD was largest in the two heaviest classes. Average WG was 1.5
      +/- 1.1 kg for winners and 1.2 +/- 1.0 kg for losers. RWG was 2.4 +/- 1.8% for
      winners and 1.9 +/- 1.6% for losers. CONCLUSIONS: The difference in WG and RWG
      between winners and losers was significant (P < 0.05). In 74 of the 130 bouts
      (57%), the heavier wrestler was successful (NS).

PMID- 9624657
TI  - Reproducibility of the acetylene rebreathe technique for determining cardiac
      output.
AB  - PURPOSE: The acetylene rebreathe technique is a well established method for the
      determination of cardiac output (Q) at rest and during exercise. We sought to
      demonstrate that the acetylene rebreathe technique allows for highly reproducible
      determinations of Q. METHODS: Nine elite male endurance cyclists (VO2max = 68.9
      +/- 0.6 mL.kg-1.min-1) performed a modified acetylene rebreathe maneuver during
      incremental exercise on four repeat test days. A key modification to the method
      originally described by Grollman was the maintenance of a positive filling
      pressure during the inhalation portion of the procedure. RESULTS: There were no
      significant differences in determinations of Q at the same submaximal heart rates
      on four separate test days. The coefficient of variation for repeat
      determinations of maximal Q during the same work rate, expressed as the standard
      deviation of the difference between duplicate measurements, is 4.8%. The
      coefficient of variation for determinations of maximal Q at the same heart rate
      on different days, expressed as the standard deviation of the difference between
      four test days, is 2.6%. CONCLUSION: These findings illustrate that the acetylene
      rebreathe technique can be used with confidence to assess Q across repeated
      experimental days.

PMID- 9624658
TI  - Validity of oxygen uptake measurements during exercise under moderate hyperoxia.
AB  - PURPOSE: The validity of oxygen uptake in hyperoxia (FIO2 = 30%) measured by an
      automated system (MedGraphics, CPX/D system) was assessed during the simulation
      of gas exchanges during exercise with a mechanical system and during submaximal
      exercise by human subjects. METHODS: The simulation system reproduced a stable
      and accurate VO2 for 30 min (sim-test). This trial was repeated nine times in
      normoxia and nine times in hyperoxia. Ten subjects also performed two submaximal
      exercises (55% of normoxic VO2max) on a cycle ergometer at the same absolute
      power in normoxia and in hyperoxia (ex-test). RESULTS: There was a significant
      downward drift of the oxygen fraction measurement in hyperoxia (< or = 0.10% for
      FIO2 and FEO2) during sim-test, but VO2 measurement remained stable in the two
      conditions. There was also a downward drift of the oxygen fraction measurement in
      the two conditions (< or = 0.07% for FIO2) during ex-test. VO2 was significantly
      higher in hyperoxia (+4.6%), and this result was confirmed using a modified
      Douglas bag method. CONCLUSIONS: These findings show that the CPX/D system is
      stable and valid for assessing VO2 in moderate hyperoxia.

PMID- 9624659
TI  - Methods for evaluating peak oxygen uptake and anaerobic threshold in upper body
      of cross-country skiers.
AB  - PURPOSE: The aim of the present study was to develop a standard protocol for
      evaluating peak oxygen uptake and anaerobic threshold during upper body work by
      cross-country skiers. METHODS: All tests were performed on a specially developed
      ski ergometer and incorporated the double poling technique. In series I,
      continuous and discontinuous protocols for measuring VO2peak at different
      inclinations of the ski ergometer were performed. In series II, a protocol for
      evaluating anaerobic threshold during upper body work was established. Eleven
      well trained regional male cross-country skiers participated in the study. All
      tests in each series were carried out during a period of 14 d. RESULTS: VO2peak
      did not differ using continuous or discontinuous protocol while working on the
      ski ergometer. Inclination was found to influence VO2peak, which was reduced at 7
      degrees compared with 3 degrees, 5 degrees, and 6 degrees. Th(an) working on the
      ski ergometer was reached at a power output, VO2, or fc, which gave on average a
      blood lactate concentration of 1.8 mmol.L-1 higher than those found after the
      warm-up period during a graded protocol. CONCLUSIONS: Testing only the
      traditional Th(an) and VO2max while running on a treadmill hides important
      determinants of endurance in cross-country skiing as shown by that no correlation
      was found between VO2max and VO2peak in the present study.

PMID- 9624660
TI  - Effect of alterations in blood volume on cardiac functioning during maximal
      exercise.

PMID- 9624661
TI  - American College of Sports Medicine Position Stand. The recommended quantity and
      quality of exercise for developing and maintaining cardiorespiratory and muscular
      fitness, and flexibility in healthy adults.
AB  - ACSM Position Stand on The Recommended Quantity and Quality of Exercise for
      Developing and Maintaining Cardiorespiratory and Muscular Fitness, and
      Flexibility in Adults. Med. Sci. Sports Exerc., Vol. 30, No. 6, pp. 975-991,
      1998. The combination of frequency, intensity, and duration of chronic exercise
      has been found to be effective for producing a training effect. The interaction
      of these factors provide the overload stimulus. In general, the lower the
      stimulus the lower the training effect, and the greater the stimulus the greater
      the effect. As a result of specificity of training and the need for maintaining
      muscular strength and endurance, and flexibility of the major muscle groups, a
      well-rounded training program including aerobic and resistance training, and
      flexibility exercises is recommended. Although age in itself is not a limiting
      factor to exercise training, a more gradual approach in applying the prescription
      at older ages seems prudent. It has also been shown that aerobic endurance
      training of fewer than 2 d.wk-1, at less than 40-50% of VO2R, and for less than
      10 min-1 is generally not a sufficient stimulus for developing and maintaining
      fitness in healthy adults. Even so, many health benefits from physical activity
      can be achieved at lower intensities of exercise if frequency and duration of
      training are increased appropriately. In this regard, physical activity can be
      accumulated through the day in shorter bouts of 10-min durations. In the
      interpretation of this position stand, it must be recognized that the
      recommendations should be used in the context of participant's needs, goals, and
      initial abilities. In this regard, a sliding scale as to the amount of time
      allotted and intensity of effort should be carefully gauged for the
      cardiorespiratory, muscular strength and endurance, and flexibility components of
      the program. An appropriate warm-up and cool-down period, which would include
      flexibility exercises, is also recommended. The important factor is to design a
      program for the individual to provide the proper amount of physical activity to
      attain maximal benefit at the lowest risk. Emphasis should be placed on factors
      that result in permanent lifestyle change and encourage a lifetime of physical
      activity.

PMID- 9624662
TI  - American College of Sports Medicine Position Stand. Exercise and physical
      activity for older adults.
AB  - ACSM Position Stand on Exercise and Physical Activity for Older Adults. Med. Sci.
      Sports. Exerc., Vol. 30, No. 6, pp. 992-1008, 1998. By the year 2030, the number
      of individuals 65 yr and over will reach 70 million in the United States alone;
      persons 85 yr and older will be the fastest growing segment of the population. As
      more individuals live longer, it is imperative to determine the extent and
      mechanisms by which exercise and physical activity can improve health, functional
      capacity, quality of life, and independence in this population. Aging is a
      complex process involving many variables (e.g., genetics, lifestyle factors,
      chronic diseases) that interact with one another, greatly influencing the manner
      in which we age. Participation in regular physical activity (both aerobic and
      strength exercises) elicits a number of favorable responses that contribute to
      healthy aging. Much has been learned recently regarding the adaptability of
      various biological systems, as well as the ways that regular exercise can
      influence them. Participation in a regular exercise program is an effective
      intervention/ modality to reduce/prevent a number of functional declines
      associated with aging. Further, the trainability of older individuals (including
      octo- and nonagenarians) is evidenced by their ability to adapt and respond to
      both endurance and strength training. Endurance training can help maintain and
      improve various aspects of cardiovascular function (as measured by maximal VO2,
      cardiac output, and arteriovenous O2 difference), as well as enhance submaximal
      performance. Importantly, reductions in risk factors associated with disease
      states (heart disease, diabetes, etc.) improve health status and contribute to an
      increase in life expectancy. Strength training helps offset the loss in muscle
      mass and strength typically associated with normal aging. Additional benefits
      from regular exercise include improved bone health and, thus, reduction in risk
      for osteoporosis; improved postural stability, thereby reducing the risk of
      falling and associated injuries and fractures; and increased flexibility and
      range of motion. While not as abundant, the evidence also suggests that
      involvement in regular exercise can also provide a number of psychological
      benefits related to preserved cognitive function, alleviation of depression
      symptoms and behavior, and an improved concept of personal control and self
      efficacy. It is important to note that while participation in physical activity
      may not always elicit increases in the traditional markers of physiological
      performance and fitness (e.g., VO2max, mitochondrial oxidative capacity, body
      composition) in older adults, it does improve health (reduction in disease risk
      factors) and functional capacity. Thus, the benefits associated with regular
      exercise and physical activity contribute to a more healthy, independent
      lifestyle, greatly improving the functional capacity and quality of life in this
      population.

PMID- 9624663
TI  - American College of Sports Medicine Position Stand and American Heart
      Association. Recommendations for cardiovascular screening, staffing, and
      emergency policies at health/fitness facilities.
AB  - The promotion of physical activity is at the top of our national public health
      agenda. Although regular exercise reduces subsequent cardiovascular morbidity and
      mortality, the incidence of a cardiovascular event during exercise in patients
      with cardiac disease is estimated to be 10 times that of otherwise healthy
      persons. Adequate screening and evaluation are important to identify and counsel
      persons with underlying cardiovascular disease before they begin exercising at
      moderate to vigorous levels. This statement provides recommendations for
      cardiovascular screening of all persons (children, adolescents, and adults)
      before enrollment or participation in activities at health/fitness facilities.
      Staff qualifications and emergency policies related to cardiovascular safety are
      also discussed.

PMID- 9624664
TI  - Why pharmacogenomics? Why now?

PMID- 9624665
TI  - Transferring EU-funded biotechnology research to European bioindustry.

PMID- 9624666
TI  - Do corporate gifts compromise biotech researchers?

PMID- 9624667
TI  - deCODE deferred.

PMID- 9624668
TI  - Unfair treatment.

PMID- 9624669
TI  - Gene therapy or antisense.

PMID- 9624670
TI  - Drug bill cuts force firms overseas.

PMID- 9624671
TI  - BMS cancer spin-off raises first finance.

PMID- 9624672
TI  - Central criminal DNA database created in Germany.

PMID- 9624673
TI  - Researcher and Amgen baffled by love letter.

PMID- 9624674
TI  - Revolution on a square centimeter.

PMID- 9624675
TI  - Shining a light on protein sociobiology.

PMID- 9624676
TI  - The ins and outs of on and off.

PMID- 9624677
TI  - DNA vaccines with a kick.

PMID- 9624678
TI  - Gene knockouts galore.

PMID- 9624679
TI  - Postgenomic protein analysis: the next bend in the river.

PMID- 9624680
TI  - Questions from a scientific audience: how do I get started?

PMID- 9624681
TI  - Valuing biotechnology assets.

PMID- 9624682
TI  - The insects are coming.

PMID- 9624683
TI  - Human antibodies by design.
AB  - Monoclonal antibodies (Mabs) have long been considered a good class of natural
      drugs, both because they mimic their natural role in the body and because they
      have no inherent toxicity. Although rodent Mabs are readily generated, their
      widespread use as therapeutic agents has been hampered because they are
      recognized as foreign by the patient. Evidently, clinical Mabs should be as human
      as possible and results with some of the more recently developed chimerized and
      humanized Mabs are testimony to this. Mabs that are entirely human are now being
      produced from phage display and transgenic mice. The first fully human Mabs
      generated by phage display have already entered clinical trials, and together
      with recent advances in these technologies, may finally realize the full
      potential of antibodies.

PMID- 9624684
TI  - Preparation and hybridization analysis of DNA/RNA from E. coli on microfabricated
      bioelectronic chips.
AB  - Escherichia coli were separated from a mixture containing human blood cells by
      means of dielectrophoresis and then subjected to electronic lysis followed by
      proteolytic digestion on a single microfabricated bioelectronic chip. An
      alternating current electric field was used to direct the bacteria to 25
      microlocations above individually addressable platinum microelectrodes. The
      platinum electrodes were 80 microns in diameter and had center-to-center spacings
      of 200 microns. After the isolation, the bacteria were lysed by a series of high
      voltage pulses. The lysate contained a spectrum of nucleic acids including RNA,
      plasmid DNA, and genomic DNA. The lysate was further examined by electronically
      enhanced hybridization on separate bioelectronic chips. Dielectrophoretic
      separation of cells followed by electronic lysis and digestion on an
      electronically active chip may have potential as a sample preparation process for
      chip-based hybridization assays in an integrated DNA/RNA analysis system.

PMID- 9624685
TI  - Bcl-2 and Bax interactions in mitochondria probed with green fluorescent protein
      and fluorescence resonance energy transfer.
AB  - It has been hypothesized that interaction of Bcl-2 and Bax may regulate
      apoptosis. The spatial and temporal interaction of Bcl-2 and Bax at the single
      cell level has not, however, been demonstrated. To achieve this goal, we have
      developed two-fusion FRET (fluorescence resonance energy transfer). Using green
      fluorescent protein (GFP)-Bax and blue fluorescent protein (BFP)-Bcl-2 fusion
      proteins coexpressed in the same cell, we demonstrate a direct interaction
      between Bcl-2 and Bax in individual mitochondria. Mitochondrially localized
      cytochrome c-GFP and BFP-Bcl-2 showed little or no FRET, while nuclear-localized
      GFP-human papillomavirus E6 and BFP-Bcl-2 did not interact when coexpressed in
      the same cell. These findings indicate that two-fusion FRET provides an
      opportunity to examine the interaction between two different proteins coexpressed
      in single intact mammalian cells.

PMID- 9624686
TI  - Switching transgene expression in the brain using an adenoviral tetracycline
      regulatable system.
AB  - We have developed a tetracycline-regulatable adenoviral transfection system that
      mediates efficient long-term transfer of genes into neuronal cells in vivo. This
      system allows gene expression to be switched on, then off, and back on again
      simply by administering or removing doxycycline from the animals' drinking water.
      This regulatable adenoviral vector system should be of value in behavioral
      studies and in vivo studies of neuronal gene function, and may further the
      development of effective gene therapy strategies in the brain.

PMID- 9624687
TI  - A nuclease-resistant protein kinase C alpha ribozyme blocks glioma cell growth.
AB  - We investigated the cleavage activity, stability, and efficacy of 2'-amino
      pyrimidine modified ribozymes on malignant glioma growth. A synthetic protein
      kinase C alpha (PKC alpha) ribozyme with complete pyrimidine nucleotide
      substitution retained a comparable cleavage activity compared with the unmodified
      ribozyme. The half-life of the modified ribozyme in serum was increased 14,000
      fold compared with the unmodified version. The PKC alpha modified ribozyme
      inhibited glioma cell growth in vitro as a result of the inhibition of PKC alpha
      gene expression. A single injection of cationic liposome ribozyme complexes into
      glioma tumors inhibited tumor growth, demonstrating both the efficacy of the
      ribozyme and a major role of PKC alpha in tumor growth.

PMID- 9624688
TI  - Enhancing immune responses using suicidal DNA vaccines.
AB  - We describe a DNA vaccine strategy that allows antigens to be produced in vivo in
      the context of an alphaviral replicon. Mice immunized with such vectors developed
      humoral and cellular immune responses at higher levels than mice that received a
      conventional DNA vaccine vector. Immunized animals acquired protective immunity
      to lethal influenza challenge. Compared with traditional DNA vaccine strategies
      in which vectors are persistent and the expression constitutive, the expression
      mediated by the alphaviral vector was transient and lytic. As a result, biosafety
      risks such as chromosomal integration, and the induction of immunological
      tolerance, could be circumvented.

PMID- 9624689
TI  - Quantitative whole-genome analysis of DNA-protein interactions by in vivo
      methylase protection in E. coli.
AB  - A global methylation-based technique was used to identify, display, and
      quantitate the in vivo occupancy of numerous protein-binding sites within the
      Escherichia coli genome. The protein occupancy profiles of these sites showed
      variation across different growth conditions and genetic backgrounds. Of the 25
      sites identified in this study, 24 occurred within 5' noncoding regions. Protein
      occupancy at 13 of these sites was supported by independent biochemical and
      genetic evidence. Most of the remaining 12 sites fell upstream of genes with no
      previously known function. A multivariate statistical analysis was utilized to
      group such uncharacterized genes with well-characterized ones, providing insights
      into their function based on a common pattern of transcriptional regulation.

PMID- 9624690
TI  - An integrated microbial process for the bioremediation of soil contaminated with
      toxic metals.
AB  - Microbially catalyzed reactions, which occur in the natural sulfur cycle, have
      been integrated in a microbiological process to remove toxic metals from
      contaminated soils. Bioleaching using sulfuric acid produced by sulfur-oxidizing
      bacteria was followed by precipitation of the leachate metals as insoluble
      sulfides by sulfate-reducing bacteria. Metal contaminants including Cd, Co, Cr,
      Cu, Mn, Ni, and Zn were efficiently leached from an artificially contaminated
      soil. Mn, Ni, and Zn were the only target elements that were significantly
      leached from soil minerals. Pb leaching was slow and remained incomplete over a
      period of 180 days. Mineral components such as Fe, Ca and Mg were also leached
      but the eventual reduction in soil mass was only approximately 10%. An
      industrially contaminated soil was also efficiently leached and approximately 69%
      of the main toxic metals present, Cu, Ni, and Mn, were removed after 175 days.
      The leachate that resulted from the action of sulfur-oxidizing bacteria on
      contaminated soil was stripped of metals using an anaerobic bioreactor containing
      a mixed culture of sulfate-reducing bacteria which precipitated soluble metal
      species as solid metal sulfides. More than 98% of the metals were removed from
      solution with the exception of Mn, Ni, and Pb, where 80-90% were removed. The
      metal content of the resultant effluent liquor was low enough to meet European
      criteria for discharge into the environment.

PMID- 9624691
TI  - Surface display of Zymomonas mobilis levansucrase by using the ice-nucleation
      protein of Pseudomonas syringae.
AB  - The ice-nucleation protein (Inp) is a glycosyl phosphatidylinositol-anchored
      outer membrane protein found in some Gram-negative bacteria. Using Pseudomonas
      syringae inp as an anchoring motif, we investigated the functional display of a
      foreign protein, Zymomonas mobilis levansucrase (LevU), on the surface of
      Escherichia coli. The cells expressing Inp-LevU were found to retain both the ice
      nucleation and whole-cell levansucrase enzyme activities, indicating the
      functional expression of Inp-LevU hybrid protein on the cell surface. The surface
      localization was further verified by immunofluorescence microscopy, fluorescence
      activated cell sorting flow cytometry and immunogold electron microscopical
      examination. No growth inhibition or changes in the outer membrane integrity were
      observed upon the induction of fusion protein synthesis. Viability of the cells
      was also maintained over 48 hours in the stationary phase. Surface-displayed
      levansucrases were found to be resistant to the externally added proteases unless
      the cells were treated with EDTA. When the levansucrase-displayed cells were used
      as the enzyme source, levan (44 g/L) was efficiently synthesized from sucrose
      (130 g/L) with 34% (wt/wt) conversion yield, generating glucose (65 g/L) as a by
      product.

PMID- 9624692
TI  - Cloning of cell-specific secreted and surface proteins by subtractive antibody
      screening.
AB  - To identify and clone genes that encode cell- or tissue-specific secreted and
      surface proteins, a polyclonal antiserum was raised against a complex mixture of
      surface or secreted proteins from the target cell, followed by immunodepletion of
      antibodies that recognize proteins from a nontarget cell or tissue. The depleted
      antiserum is used to screen bacteriophage cDNA expression libraries. Because of
      our interest in how adipocytes communicate with other cells, we have used this
      method to clone cDNAs encoding secreted and plasma membrane proteins that are
      induced during adipocyte differentiation. We describe several of these, including
      a novel plasma membrane-associated protein, S3-12.

PMID- 9624693
TI  - Extremophiles.

PMID- 9624694
TI  - Vision therapy to reduce abnormal nearwork-induced transient myopia.
AB  - After brief periods of nearwork, some younger patients complain of transient
      distance blur that is correlated with a transient pseudomyopic shift in their
      distance refraction. This phenomenon has recently been documented objectively.
      However, there is lack of objective documentation demonstrating the effects of
      conventional optometric vision therapy in symptomatic individuals manifesting
      this "abnormal nearwork-induced transient myopia" (ANITM). Five symptomatic
      subjects received 7 to 10 weeks (5 to 6 sessions) of accommodative facility
      vision therapy (i.e., lens flippers and Hart chart). Objective recording of their
      ANITM and its decay were taken before and after the vision therapy, using a Canon
      R-1 autorefractor. A daily log was maintained, describing qualitatively their
      nearwork-related symptomatology. After therapy, there was marked reduction of
      symptoms and considerable improvement in clinical accommodative facility
      measures, as well as improvement in the objective findings. These results
      demonstrate multi-faceted positive effects of optometric accommodative vision
      therapy in this diagnostic group of symptomatic individuals.

PMID- 9624695
TI  - Fluorophotometry in contact lens research: the next step.
AB  - BACKGROUND: Fluorophotometry can be used to quantify changes in epithelial
      permeability (Pdc), corneal pH, and tear exchange (T95; time to deplete 95% of a
      fluorescent dye from beneath a contact lens) associated with contact lens wear.
      Using fluorometric procedures, we present previously reported data in order to
      review the effects of contact lens wear on Pdc and pH. We also introduce a new
      method for measuring tear exchange beneath a soft contact lens and present
      preliminary data. METHODS: Pdc was assessed on 32 subjects after 1 h of closed
      eye soft contact lens wear. Stromal pH was assessed on 21 subjects wearing lenses
      with a range of different oxygen transmissibilities (Dk/L). T95 was assessed on 7
      subjects who wore disposable lenses. Pdc estimates were derived by measuring the
      rate at which topically applied fluorescein crossed the epithelial barrier from
      the tears; corneal pH was quantified by alternately exciting a fluorescein-loaded
      cornea with two wavelengths of blue light and calculating the fluorescence
      intensity ratio (490/450 nm), which is pH-sensitive; and the T95 was estimated by
      applying 2 microliters of FITC-Dextran to the posterior surface of a soft contact
      lens and the monitoring the exponential decay of dye under the lens. RESULTS: On
      average, 1 h of closed-eye contact lens wear caused a 41% increase in Pdc
      compared to the control eye. Corneal pH varied directly with a decrease in Dk/L.
      On average the T95 under contact lenses (mean = 29 min) was slow compared to
      normal rates with no lens (approximately 5 min). CONCLUSIONS: Fluorophotometry
      can be used to quantify some interesting effects associated with contact lens
      wear, and the use of these techniques may provide new information about the
      impact of contact lens wear on corneal structure and function.

PMID- 9624696
TI  - Comparison by contact lens cytology and clinical tests of three contact lens
      types.
AB  - PURPOSE: To determine if hydrogel lens materials from different FDA groups have
      different effects on the human ocular surface. METHODS: Contact lenses from
      Groups I and II, and Group IV were tested on 10 healthy adapted hydrogel contact
      lens wearers. For each comparison, the subject wore 2 new contact lenses for
      approximately 45 min. Lens movement was measured, and comfort evaluated using a
      subjective scale. After removal of the lenses, fluorescein staining and tear
      break-up time were measured. Cells were collected by contact lens cytology (CLC),
      and the size and number of cells harvested from each lens were determined.
      RESULTS: There were differences between lens groups in lens movement and comfort,
      but no differences in fluorescein staining or tear break-up time. CLC showed no
      differences in cell counts or cell size. There was no correlation between the
      results of CLC and the clinical tests for lens movement, lens comfort, tear break
      up time, and fluorescein staining. CONCLUSIONS: With short durations of lens
      wear, differences in ionicity and water content have no effect upon the size and
      number of cells collected from a contact lens. This suggests that, in the short
      term, the shedding of cells beneath a hydrogel lens is not affected by the
      choices of lens material.

PMID- 9624697
TI  - Effects of lacrimal drainage occlusion with nondissolvable intracanalicular plugs
      on hydrogel contact lens wear.
AB  - PURPOSE: To investigate effects of lacrimal drainage occlusion with
      intracanalicular silicone plugs in hydrogel lens wearers with the symptom of
      dryness. Effects of rewetting drops in combination with the plugs were also
      evaluated. METHODS: A 6-week, prospective, double masked, placebo-controlled
      study design was followed. Thirty-five patients (26 females and 9 males) were
      entered into the study based on specific symptoms and signs of dry eye with
      hydrogel lens wear. Baseline symptoms, noninvasive prelens tear film break-up
      time, lens water content, fluorescein, and rose bengal staining were recorded.
      Herrick Lacrimal Plugs were inserted into both canaliculi of one previously
      randomized eye by an independent investigator. The fellow eye was manipulated in
      a sham procedure. Symptoms and signs were followed over 4 weeks. Nonpreserved
      rewetting drops were used in both eyes during the 5th week. Symptoms and signs
      were again followed. RESULTS: Symptoms improved more significantly in the plugged
      eye than the control eye after insertion of the plugs, and again after use of the
      drops. This improvement diminished in some of the patients. Prelens tear film
      break-up time was not significantly changed. Water content of all lenses combined
      increased only in the plugged eye with the use of drops. Fluorescein staining
      decreased significantly in the plugged eye. Rose bengal staining showed a slight
      decrease in the plugged eye. CONCLUSIONS: Intracanalicular silicone plugs offer
      improvement of symptoms and signs of dryness in this population. There seems to
      be some decrease in improvement of symptoms with the plugs over time. Concurrent
      use of rewetting drops increases the benefits.

PMID- 9624698
TI  - Rose bengal dye concentration and volume delivered via dye-impregnated paper
      strips.
AB  - PURPOSE: The technique of administration and the resulting volume and
      concentration of the dye delivered to the eye via dye-impregnated paper strips
      are not standardized or known. The purpose of this study was to use a standard
      technique for preparation of rose bengal dye from commercially available paper
      strips to determine the variability in concentration based upon soak time, and to
      determine the volume delivered by such a technique to a model eye. METHODS: Rose
      bengal filter paper strips were wetted for either 15, 30, or 45 s, and the
      resulting concentration of dye eluted was determined by spectrophotometry. With
      the same preparation technique and a 15-s soak time, the strip was applied to
      wetted filter paper, as a model for the moist surface of the eye. The volume of
      solution delivered was calculated by weight. RESULTS: Concentrations of rose
      bengal for the various soak times were: 15 s: 7.64 (+/- 1.11) by 10(-6) g/ml; 30
      s: 9.70 (+/- 1.79) by 10(-6) g/ml; and 45 s: 10.27 (+/- 0.66) by 10(-6) g/ml. The
      volume delivered to the eye model with this technique was 17.43 microliters (+/-
      3.09). CONCLUSIONS: The concentration of rose bengal dye delivered to the ocular
      surface by means of a wetted strip is relatively low and soak time/technique
      dependent. This suggests a possibility that results in clinical studies with rose
      bengal strip application may be different than if controlled volume applications
      of commercially available 1% liquid rose bengal dye are used.

PMID- 9624699
TI  - Repeatability of visual acuity measurement.
AB  - PURPOSE: This study investigates features of visual acuity chart design and
      acuity testing scoring methods which affect the validity and repeatability of
      visual acuity measurements. METHODS: Visual acuity was measured using the Sloan
      and British Standard letter series, and Landolt rings. Identifiability of the
      different letters as a function of size was estimated, and expressed in the form
      of frequency-of-seeing curves. These functions were then used to simulate acuity
      measurements with a variety of chart designs and scoring criteria. RESULTS:
      Systematic relationships exist between chart design parameters and acuity score,
      and acuity score repeatability. In particular, an important feature of a chart,
      that largely determines the repeatability of visual acuity measurement, is the
      amount of size change attributed to each letter. The methods used to score visual
      acuity performance also affect repeatability. CONCLUSIONS: It is possible to
      evaluate acuity score validity and repeatability using the statistical principles
      discussed here.

PMID- 9624700
TI  - A systems model for low vision rehabilitation. II. Measurement of vision
      disabilities.
AB  - BACKGROUND: This study presents and tests a method of measuring vision
      disabilities. Based on the model presented in the first paper of this series,
      cognitive and motor activities ("tasks") are organized in a hierarchy that
      identifies the tasks' behavioral goals (purposes) and the social objectives the
      goals serve. Two latent variables important to the definition of vision
      disability are identified: "value of living independently" and "visual ability
      for independent living." The basic principles of the Rasch measurement model are
      reviewed, and Rasch models are used to measure the two variables that define
      vision disability. The need for rehabilitation to meet each goal is represented
      by "rehabilitative demand," a mathematical function of the measurements made of
      the value and difficulty of achieving each goal independently. METHODS: Over 400
      patients with low vision rated both the importance and difficulty of
      independently achieving each of 24 goals. Rasch analysis was used to derive
      interval measures of the social value of each goal, the value that individual
      patients placed on each goal relative to the derived social definition of
      independence, the visual ability required to achieve each goal without help, and
      the visual ability of individual patients to live independently. A rehabilitative
      demand function was ascertained from the judgments of 17 AAO Diplomates in Low
      Vision through triadic comparisons and multidimensional scaling. RESULTS: Self
      care had the greatest "social value" for independence; performing music had the
      least. Recreational reading required the greatest "visual ability" to accomplish
      independently; self-care required the least. Rehabilitative demand was linear
      with value and nonmonotonic with difficulty. CONCLUSIONS: Rehabilitative demand,
      an algorithm for defining vision disability, incorporates interval measures of
      visual ability and the value of independent living estimated from patient-based
      assessments, a social scale of the value of activities relative to independent
      living, and a consensus opinion of low vision experts on the prioritization of
      the need for rehabilitation.

PMID- 9624701
TI  - Repetition priming and experimental context effects.
AB  - The repetition priming effect has been taken as evidence that lexical entries are
      automatically activated in memory. However, contextual cues in an experiment may
      influence repetition priming, suggesting that this priming may not be the result
      of automatic processes. Five experiments used a primed shadowing task to explore
      the role of phonological context on repetition priming. In the first four
      experiments, high- and low-expectancy conditions were tested. Between
      experiments, the degree of phonological relatedness (high or low phonological
      similarity), percentage of related trials that were repetition trials (ID ratio),
      and modality of stimulus presentation (auditory or visual) were manipulated.
      Results indicate that repetition priming in auditory word recognition is
      eliminated by a low ID ratio. The fact that an external variable such as the ID
      ratio influences repetition priming suggests that repetition priming may be the
      product of processes extraneous to the automatic activation of lexical entries.

PMID- 9624702
TI  - Metamemory accuracy: effects of feedback and the stability of individual
      differences.
AB  - This study addressed two questions about metamemory accuracy: how feedback about
      recall performance affects confidence-recall accuracy and whether individual
      differences in confidence-recall accuracy are stable across different sets of
      test items. College students answered general knowledge questions and made
      confidence ratings about the correctness of the answers. Half the students were
      told whether their answers were correct. All students answered half the questions
      a second time. The results show that feedback did not produce a general
      improvement in metamemory accuracy; the improvement was specific to the questions
      for which feedback was provided. Also, individual students' metamemory accuracy
      showed moderate alternate-forms stability when each test was made up of 250
      items. Therefore, researchers studying individual differences in metamemory
      accuracy on recall tasks should use tests that yield several hundred responses.

PMID- 9624703
TI  - The roles of cue and target familiarity in making feeling of knowing judgments.
AB  - This study evaluated the effects of cue and target familiarity on metacognitive
      judgments by using a retroactive interference paradigm. Subjects studied 12 pairs
      of unrelated words. The first 6 pairs formed an A-B list, and the next 6 formed
      an A-B list (both elements repeated), a C-B list (only the target repeated), an A
      D list (only the cue repeated), or a C-D list (neither element repeated).
      Following study, the six critical cues were presented and subjects made
      predictions of knowing. Predictions were highest when both elements were repeated
      and equally low when only the cue, only the target, or neither element was
      repeated. A subsequent cued recall test showed that significant retroactive
      interference effects were apparent. The findings suggest that neither cue nor
      target familiarity alone sufficiently explains knowing judgments.

PMID- 9624704
TI  - Dual-mode presentation and its effect on implicit and explicit memory.
AB  - We empirically investigated whether the auditory and visual subsystems mediating
      priming interact. We examined the hypothesis that processing in the visual
      subsystem during an implicit memory test permits access to memories in the
      auditory subsystem that were stored concurrently with visual memories. We did so
      by comparing priming in visual perceptual identification following both visual
      and auditory presentation (multimodal priming), only visual presentation (within
      modality priming), or only auditory presentation (cross-modality priming). We
      focused on the comparison between multimodal and within-modality priming because
      multimodal priming should be larger than within-modality priming under our
      hypothesis. However, multimodal priming was approximately equal to within
      modality priming in four experimental conditions. These results are consistent
      with the view that there is limited interaction between the visual and auditory
      subsystems mediating priming.

PMID- 9624705
TI  - Multiple interference effects in short-term recognition memory.
AB  - Five experiments, using a probe recognition procedure, examined the codes
      involved in short-term memory. Interference effects were obtained for probes with
      an orthographic, associative, or semantic relationship to a memory set item. The
      orthographic interference effects appeared to result from matches on the basis of
      abstract letter codes (i.e., graphemes) rather than overlap of visual features.
      The associative and semantic effects differed from what might be predicted on the
      basis of spreading activation, suggesting that these effects are qualitatively
      different from semantic priming effects observed in lexical decision tasks. These
      results support models of short-term memory in which items are represented as
      groups of features and recognition depends on a comparison of the features of the
      probe to those of the memory set items.

PMID- 9624706
TI  - The circumstances and prevention of bar-glass injury.

PMID- 9624707
TI  - Conversation with Reg Smart.

PMID- 9624708
TI  - Ivan Bratt: the man who saved Sweden from prohibition.
AB  - For forty years, until 1955, spirits were rationed in Sweden under a system of
      individual control. Local "System companies" had a monopoly on the retail trade
      in spirits and wine. Private profits on alcohol were also eliminated in the
      restaurants and the wholesale trade. Legislation was based on the proposals put
      forward by the physician Ivan Bratt (1878-1956), who presented his ideas in 1909
      as an alternative to prohibition. Bratt had the support of leading personalities
      in Swedish medicine, newspapers and politics, and he also enlisted the support of
      some of the leaders of the powerful temperance movement. In 1922, Swedes voted
      against prohibition in a referendum by 51% to 49%. The Bratt system substantially
      reduced alcohol abuse. When it was abolished, drunkenness in the streets doubled.
      By 1960, when high taxes had replaced rationing as the policy for controlling the
      consumption of alcohol, delirium tremens had increased since the Bratt period
      from 160 cases a year to 700 cases a year.

PMID- 9624709
TI  - Nesbitt's Paradox resolved? Stress and arousal modulation during cigarette
      smoking.
AB  - Nesbitt's Paradox states that cigarette smoking generates physiological and
      psychological changes which are normally incompatible, namely increased arousal
      together with decreased stress. This review confirms these changes, but shows
      that they are dependent upon various factors, particularly the degree of nicotine
      deprivation. Thus the relaxant properties of smoking reflect the relief of
      irritability which develops between cigarettes. The deleterious mood effects of
      abstinence explain why smokers suffer more daily stress than non-smokers, and
      become less stressed when they quit smoking. Deprivation reversal also explains
      much of the arousal data, with deprived smokers being less vigilant and less
      alert than non-deprived smokers or non-smokers. Nicotine can, however, display
      genuine stimulant properties, although due to repeated abstinence effects the
      average arousal level of smokers is generally similar to non-smokers. Mood
      normalization also explains why nicotine is so addictive, with regular smokers
      needing nicotine just to "function" normally. Finally, Nesbitt's Paradox also
      assumes that arousal and emotionality are associated with each other. Yet factor
      analysis of mood and personality questionnaires shows that these two dimensions
      are statistically independent, with the stress and arousal changes during smoking
      also generally uncorrelated. Nesbitt's Paradox is therefore not actually a
      paradox; it never was a paradox.

PMID- 9624710
TI  - The early course of change in methadone maintenance.
AB  - AIMS: This study examined the functional and substance use status of methadone
      maintenance (MM) patients at treatment entry and 2 and 7 months later. DESIGN:
      Two groups of subjects were identified for longitudinal follow-up, those in
      continuous MM treatment and those who left treatment. SETTING: The study was
      conducted at the Philadelphia Veterans Affairs Medical Center MM Program.
      PARTICIPANTS: Subjects were 157 men admitted to treatment. MEASUREMENTS: Change
      was evaluated using the Addiction Severity Index and urinalysis results.
      FINDINGS: Both groups of subjects reported significant reductions in drug use and
      increases in psychosocial functioning from admission to month 2, but demonstrated
      no significant changes from months 2 to 7. Subjects who left treatment, however,
      had more heroin use and criminal activity at all evaluation points than subjects
      who remained in treatment. Urinalysis data also suggested that subjects who left
      treatment were using drugs more frequently while in treatment than were those
      subjects who remained continuously enrolled in MM. Finally, subjects who left
      treatment spent more time in restricted environments (e.g. inpatient treatment,
      jail) at follow-up. CONCLUSIONS: Services may need to be enhanced to foster
      continuing progress in patients who remain in MM treatment and to retain those
      patients with more severe problems who leave treatment early.

PMID- 9624711
TI  - Pre- and in-treatment predictors of retention in methadone treatment using
      survival analysis.
AB  - AIMS: To determine the effects of pre- and in-treatment variables on patient
      retention in methadone treatment. DESIGN: Retrospective longitudinal study of an
      admission cohort sample for up to 3 years of treatment or until discharge.
      SETTING: Six methadone maintenance programs operating 15 clinics in New York
      City. PARTICIPANTS: A sample of 1206 admissions to these clinics during 1989-90.
      MEASUREMENTS: Data were abstracted from patients' medical charts. Time in
      treatment for up to 3 years was the dependent variable, analyzed as a survival
      function. Pretreatment variables were: gender, race/ethnicity, age at admission,
      employment, education, marital status, living arrangements, child care
      responsibility, criminal justice status, life-time arrests, referral source, age
      at first heroin use, polydrug use, route of drug administration, mental health
      status and methadone treatment history. In-treatment variables were: patient
      problems during treatment, clinic response to patient problems, patient treatment
      strengths, methadone dosage, heroin use and cocaine use. FINDINGS: The estimated
      median treatment duration was 23 months. Cox proportional hazards modeling
      determined that two pretreatment variables (older age and no criminal justice
      involvement) were associated with longer retention in treatment. Among in
      treatment variables, constructive clinic responses to patient problems, higher
      methadone dosage, more patient treatment strengths and less heroin and cocaine
      use during treatment were associated with longer retention. CONCLUSIONS: Events
      during treatment are crucial for patient retention in methadone treatment. Only
      two of 16 pretreatment variables, compared with five of six during-treatment
      variables, had significant effects on length of stay in a multivariate model.

PMID- 9624712
TI  - Differentiation in the Amsterdam methadone dispensing circuit: determinants of
      methadone dosage and site of methadone prescription.
AB  - AIMS: To evaluate the Methadone Dispensing Circuit in Amsterdam by identifying
      determinants of methadone dosage and client characteristics in the different
      types of methadone programmes. DESIGN AND PARTICIPANTS: Four hundred and forty
      four participants of a cohort study of drug users in Amsterdam who had consented
      to link data of the Central Methadone Register to the cohort data. FINDINGS: From
      1985 to 1994, methadone dosage increased from 41 to 59 mg/day. The mean methadone
      dosage was higher for ethnic West Europeans, Germans, older drug users, HIV
      positive drug users, those with a longer duration of prostitution, current
      injectors, those with a longer duration of injecting, longer duration of
      methadone use, higher frequency of being dispensed methadone and clients of the
      prostitutes' and foreigners' outpatient clinic. For clients of the general
      practitioner, at the police station and in prison the methadone dosage was lower.
      We found different sets of client characteristics in those receiving methadone at
      the methadone outpost, the methadone bus, the prostitutes' and foreigners'
      outpatient clinic, the general practitioner and the outdoor addiction clinic.
      CONCLUSIONS: These results indicate that the Amsterdam system is highly
      differentiated in a way that is largely concordant with the intended general
      policy on methadone treatment.

PMID- 9624713
TI  - A meta-analysis of predictors of continued drug use during and after treatment
      for opiate addiction.
AB  - AIMS: Many people treated for opiate addiction continue to use drugs during and
      after treatment. It may be possible to improve outcomes by addressing patient
      characteristics that predict continued drug use. This review uses meta-analytic
      techniques to identify risk factors for continued drug use in patients treated
      for opiate abuse. DESIGN AND MEASUREMENTS: A thorough search of the published
      literature yielded 69 studies that reported information on the bivariate
      association between one or more independent variables and continued use of
      illicit drugs during and after treatment for opiate addiction. FINDINGS: Most of
      the patient variables summarized have weak longitudinal relationships with
      continued drug use, although several variables display moderate longitudinal
      associations. Ten variables show statistically significant and longitudinally
      predictive relationships (average r > 0.1) with continued use, including: high
      level of pretreatment opiate/drug use, prior treatment for opiate addiction, no
      prior abstinence from opiates, abstinence from/light use of alcohol, depression,
      high stress, unemployment/employment problems, association with substance abusing
      peers, short length of treatment, and leaving treatment prior to completion.
      Several other variables may be potentially longitudinally predictive.
      CONCLUSIONS: To prevent relapse, treatment interventions should address multiple
      variables because no single variable strongly predicts continued drug use.

PMID- 9624714
TI  - Clinical significance of Cloninger's classification in a sample of alcoholic
      Spanish men.
AB  - AIMS: To evaluate Cloninger's classification in a sample of alcoholic Spanish
      men. DESIGN: A cross-sectional study was carried out on subjects diagnosed as
      alcoholics. SETTING: Out-patient units specializing in the treatment of
      alcoholics and the psychiatry unit of a general hospital. PARTICIPANTS: One
      hundred and ninety-eight males diagnosed as alcoholics. The mean age was 44.4 +/-
      11.6 years and 98% were from urban areas. MEASUREMENTS: Participants were
      interviewed using the Structured Clinical Interview for DSM-III-R(SCID). They
      were classified using type 1 and type 2 criteria of Cloninger's classification.
      FINDINGS: Only one-third of our sample could be classified by Cloninger's type 1
      and type 2 criteria. Patients classified as belonging to type 2 had an earlier
      onset of regular drinking compared to type 1 patients. Type 2 subjects presented
      a higher percentage of alcohol-related problems as well as problems related to
      drugs other than alcohol and they also presented a higher percentage of
      antisocial personality disorder. No differences in alcoholism family history were
      found between the groups. Criteria showing the poorest discriminative ability
      between both groups were "failure to keep abstinent" and "benders lasting at
      least two days". CONCLUSIONS: Our results do not support Cloninger's etiological
      hypotheses for alcoholism. Cultural differences may be responsible for the
      different drinking patterns observed.

PMID- 9624715
TI  - Male drinking and violence-related injury in the emergency room.
AB  - AIMS: To present epidemiological measures of associations between violence
      related injuries (assaults and fights), alcohol consumption prior to the event,
      and drinking patterns among males attending hospital emergency rooms (ERs) in
      Mexico City. DESIGN: All patients were interviewed and breath tested for alcohol
      consumption. The data were analyzed using a case-control design. SETTING: Eight
      ERs in Mexico City that were representative of the types of emergency care
      systems available in that city (from public, private and social security systems
      hospitals). PARTICIPANTS: Cases were males patients (n = 445) admitted to the ER
      because of a fight or an assault. The control group was comprised of patients (n
      = 320) admitted to the ER because of accidents that are less frequently reported
      a alcohol-related (i.e. work-place accidents, animal bites or recreational
      accidents excluding near drowning). MEASUREMENTS: A breath sample to estimate
      BAG, as well as an interviewer-administered questionnaire were used. FINDINGS:
      Alcohol consumption prior to injury was found to be a more important risk factor
      than usual drinking for injuries resulting from violence, while quantity of usual
      alcohol consumption was more predictive of violence-related injuries than
      frequency of drinking. CONCLUSIONS: These data suggest the importance of using
      more appropriate control groups when estimating associations of alcohol and
      violence-related injuries so that associations will not be underestimated. More
      research is needed to establish unbiased estimates of alcohol-related violence.

PMID- 9624716
TI  - Sample selection bias in the emergency room: an examination of the role of
      alcohol in injury.
AB  - AIMS: Injury location, injury cause and patient drinking patterns were used to
      predict blood alcohol content (BAC) and self-reported drinking before injury
      using emergency room (ER) data. DESIGN: Models estimating both BAC and self
      reported drinking among emergency room injury patients were used; the ER sample
      was also compared to an injured sample from the general population. SETTING: Data
      were from three of six communities participating in the project "Preventing
      Alcohol Trauma: a community trial". PARTICIPANTS: ER data were collected from
      nine hospitals on Friday and Saturday nights between 6 p.m. and 2 a.m. on
      alternate weekends from June 1992 to December 1995. Telephone survey data were
      collected between April 1992 and March 1996. MEASUREMENTS: Drinking measures
      included drinking frequency, drinks per occasion, and variance. Other measures
      involved injury time, location, and type; drinking before and after injury; and
      age, race, gender, education, marital status and household income. Model
      estimation corrected both for selection bias and censoring of the dependent
      measure. FINDINGS: The results indicate: (1) ER populations tended to be female,
      less well educated, non-white, poor and younger; (2) there were significant
      selection bias effects in the ER sample; (3) assaults were more likely to involve
      drinking than other injury types; (4) drinking patterns were significant non
      linear predictors of alcohol involvement; and (5) self-reported drinking before
      injury was both a sensitive and specific indicator of measured BAC. CONCLUSIONS:
      Assaults uniquely involve the use of alcohol and selection bias may threaten ER
      study validity.

PMID- 9624717
TI  - Efficacy of disulfiram: a reply to Hughes and Cook.

PMID- 9624718
TI  - Unstable pragmatism: Dutch drug policy under national and international pressure.

PMID- 9624719
TI  - Why do people change addictive behavior? The 1996 H. David Archibald Lecture.
AB  - Although there are specialty journals and professions focusing on addictions
      treatment, the reasons why people change addictive behaviors are still not well
      understood. The simplistic account that people change because they receive
      treatment is wanting in many ways. Many people who recover do so without formal
      treatment. Even relatively brief interventions seem to trigger change, and the
      dose of treatment delivered is surprisingly unrelated to outcomes. Client
      compliance with many different approaches, including placebo medication, has been
      linked to better outcomes. Client outcomes also vary widely depending upon the
      therapist who delivers treatment. Various models are briefly considered that may
      help in understanding this intriguing puzzle of change.

PMID- 9624720
TI  - The "improved" public house, 1870-1950: the key to civilized drinking or the
      primrose path to drunkenness?
AB  - The Victorian temperance movement aimed to eliminate, not reform, public houses,
      but from 1870 interest began to be taken in promoting an "improved" public house
      which could promote counter-attractions to drink. Disinterested management, based
      upon public ownership or a trust company, was advocated as the best means of
      achieving this. There was, however, an ambiguity about the nature of the
      "improved" public house. Was the goal an austere establishment where the drinking
      could be controlled in the public interest, or was it a comfortable leisure
      centre which would promote civilized drinking? This ambiguity lay unresolved
      during the period of the Carlisle experiment in state control in the period after
      1915. Increasingly during the inter-war years the policies of the state-run
      Carlisle scheme and the more go-ahead brewers converged. The issue was originally
      conceptualized as a moral one, then as one of national efficiency and finally as
      a commercial one.

PMID- 9624721
TI  - Alcohol consumption and mortality. I. Characteristics of drinking groups.
AB  - AIMS: This is the first of a set of three papers evaluating drinking status and
      mortality risk. Analyses of multiple studies describe associations of drinking
      patterns with characteristics hypothesized to confound the relationships between
      drinking status and mortality. Characteristics which both significantly
      differentiate drinking groups and are consistent across studies would suggest
      that mortality studies not controlling for them may be compromised. DESIGN AND
      PARTICIPANTS: Associations are evaluated from the raw data of 10 general
      population studies which contained mortality data. Long-term abstainers are
      compared to former drinkers, long-term abstainers and former drinkers are
      compared to light drinkers (by quantity, frequency and volume in separate
      analyses) and moderate to heavy drinkers are compared to light drinkers.
      Tetrachoric correlation coefficients assess statistical significance; meta
      analysis determines if associations are homogeneous across studies. MEASUREMENTS:
      Measures of alcohol consumption are quantity, frequency and volume; long-term
      abstainers are differentiated from former drinkers. Multiple measures of health,
      social position, social integration and mental health characteristics are
      evaluated. FINDINGS: Across studies, adult male former drinkers are consistently
      more likely to be heavier smokers, depressed, unemployed, lower SES and to have
      used marijuana than long-term abstainers. Adult female former drinkers are
      consistently more likely to be heavier smokers, in poorer health, not religious,
      and unmarried than long-term abstainers. Both types of abstainers tend to be of
      lower SES than light drinkers and report poorer health (not consistent). Female
      abstainers are more likely to be of normal or overweight than light drinkers.
      CONCLUSIONS: Characteristics of two groups of abstainers, other than their non
      use of alcohol, may confound the associations found between drinking and
      mortality risk.

PMID- 9624722
TI  - Alcohol consumption and mortality. II. Studies of male populations.
AB  - AIMS: This is the second of a set of three papers evaluating drinking status and
      mortality risk. Analysis of eight general population surveys of men evaluated all
      cause mortality rates by drinking pattern. DESIGN AND PARTICIPANTS: Raw data from
      three studies of youth and five studies of adults were evaluated. Logistic
      regression models controlled for confounding characteristics. Meta-analysis
      combined study results. MEASUREMENTS: Drinking pattern was alternatively defined
      by quantity, frequency and volume of drinking. Final models included drinking
      pattern (as well as abstinence in the youth models and long-term abstainers and
      former drinkers in adult models), age and other confounding variables. Models
      also evaluated interactions of age and, respectively, long-term abstinence and
      former drinking. FINDINGS: No evidence was found for the hypothesis that
      abstinence is associated with greater mortality risk than light drinking. In the
      youth samples, abstainers had a lower risk of dying than those drinking less than
      15 times per month. One study of the adult samples showed a significant age by
      former drinker interaction; this did not alter the lack of association of former
      drinking with mortality risk or the homogeneity of results across studies for
      this finding. The most consistent finding was the association of heavy drinking
      with mortality among youth. Among adults, drinking 43 or more drinks per month
      and drinking 21 or more times per month were associated with increased mortality
      risk. Quantity per occasion was not significantly associated with mortality risk
      among adults. CONCLUSIONS: That frequent drinking was related to mortality risk,
      whereas heavier quantity was unrelated, is inconsistent with the belief that
      daily consumption of a few glasses of wine has salutary effects. Empirically,
      however, this pattern tends to be unusual. Findings were homogeneous across
      studies lending generalizability to results.

PMID- 9624723
TI  - Alcohol consumption and mortality. III. Studies of female populations.
AB  - AIMS: This is the third of a set of three papers evaluating drinking status and
      mortality risk. Analysis of three general population surveys of women evaluated
      all-cause mortality rates by drinking pattern. DESIGN AND PARTICIPANTS: Raw data
      from three studies of adult women were evaluated. Logistic regression models
      controlled for confounding characteristics. Meta-analysis combined study results.
      MEASUREMENTS: Drinking pattern was alternatively defined by quantity, frequency
      and volume of drinking. Final models included drinking pattern (including long
      term abstainers and former drinkers) as well as age and other confounding
      variables. Models also evaluated interactions of age and, respectively, long-term
      abstinence and former drinking. FINDINGS: In models in which age was controlled,
      odds of death for long-term abstainers and former drinkers (defined by volume or
      quantity) were greater than those for light drinkers; odds of death for moderate
      and heavy drinkers (defined by quantity) were greater than those for light
      drinkers. When other psychosocial attributes were controlled, odds of death were
      similar for abstainers and light drinkers. When other psychosocial attributes
      were controlled, odds of death for heavy drinkers (defined by volume and
      quantity) were greater than those for light drinkers. When interactions of age
      and the two forms of abstinence were introduced, one study showed a significant
      effect of age and former drinking. CONCLUSIONS: Results were consistent with the
      hypothesis that characteristics of abstainers other than their non-use of alcohol
      may account for their higher mortality risk. With the exception of former
      drinkers compared to light drinkers, when interactions were introduced into
      models (for measures of quantity and frequency) findings were homogeneous across
      studies, lending generalizability to results.

PMID- 9624724
TI  - Associations between work stress, alcohol consumption and sickness absence.
AB  - AIMS: To test an interactional model on the associations between work stressors,
      perceived stress, alcohol consumption and sickness absence. DESIGN: Cross
      sectional survey. SETTING: The study was part of a Worksite Health Project
      including an Employee Assistance Programme and a Health Promotion Programme in
      the Netherlands. PARTICIPANTS: Participants were blue-collar workers from two
      Municipal Garbage Collecting Departments and white-collar workers from a
      Pharmaceutical Company (N = 471). MEASUREMENTS: Measurements included socio
      demographic characteristics (gender, age, education, marital status), work
      stressors, perceived stress, alcohol consumption and sickness absence. Type of
      work-site (blue- or white-collar) and smoking behaviour were used as covariates.
      FINDINGS: Regression analyses resulted in three major findings. First, in the
      presence of stress, abstinence increased the risk of sickness absence compared
      with moderate drinking. We failed to find a significant relationship between
      excessive drinking and sickness absence. Secondly, stress mediated the
      associations between stressor and alcohol consumption, and between stressor and
      sickness absence, although stressors also directly predicted sickness absence.
      CONCLUSIONS: The association between abstinence and sickness absence could
      reflect medical problems of abstainers or a lack of skills for coping with
      stress. The failure to find a significant detrimental effect of excessive
      drinking may have been due to use of a low threshold for excessive drinking
      and/or low power. Prospective studies are needed to gain insight in causal
      relationships between the variables concerned.

PMID- 9624725
TI  - A survey of bloodborne viruses and associated risk behaviours in Greek prisons.
AB  - AIMS: To determine HIV and hepatitis infection prevalence and correlates with
      risk behaviour. DESIGN: Cross-sectional study: voluntary, anonymous HIV,
      hepatitis (HCV, HBV and HDV) surveillance and questionnaire on risk factors.
      SETTING: Korydallos Prison, Athens and Ag. Stefanos Prison, Patra, Greece.
      PARTICIPANTS: Of 544 drug users imprisoned for drug related offences, all
      completed the questionnaire and 533 blood samples were collected. MEASUREMENTS:
      HIV (by anti-HIV-1), HCV (by anti-HCV), HBV (by anti-HBc, HBsAg) and HDV (by anti
      HDV) prevalence. Data on demography, legal status, drug use, sharing of injecting
      equipment. FINDINGS: Of the 544 drug users, 375 (68.9%) had injected drugs (IDUs)
      at some time, 35% of whom had injected whilst in that prison. Of the 533 blood
      samples tested, one was positive for anti-HIV-1 (0.19%), 310 for anti-HCV
      (58.2%), 306/531 (57.6%) for anti-HBc, 34/527 (6.5%) for HBsAg and 12/527 (2.3%)
      for anti-HDV. Prevalence rates for IDUs only were 0.27% for HIV-1, 80.6% for
      hepatitis C, 62.7% for hepatitis B and 3.3% for hepatitis D. Ninety-two per cent
      of IDUs injecting in prison shared needles, indicating that IDUs inject less but
      share more during incarceration. Multiple logistic regression revealed needle
      sharing as the most important risk factor for HCV infection in IDUs. Prior
      knowledge of a positive hepatitis result did not appear to inhibit IDUs from
      practising risky behaviours in prison. CONCLUSIONS: The epidemic of hepatitis B
      and C among imprisoned IDUs identified by this study constitutes a major public
      health problem. Prevention programmes, such as counselling, HBV vaccination,
      community-based methadone maintenance treatment and syringe exchange schemes, are
      necessary in order to prevent a further spread.

PMID- 9624726
TI  - Multi-site samples of injecting drug users in Edinburgh: prevalence and
      correlates of risky injecting practices.
AB  - AIMS: To estimate the frequency of injecting and prevalence of equipment sharing
      and other risky injecting practices among intravenous drug users (IDUs) and to
      identify correlates of these behaviours. DESIGN: Three cross-sectional surveys of
      IDUs by face-to-face interview in the years 1992-94. SETTING: Multiple treatment
      and non-treatment sites throughout the city of Edinburgh, Scotland, UK.
      PARTICIPANTS: Six hundred and thirty-four interviews of 480 IDUs who reported
      having injected a drug in the previous six months. MEASUREMENTS: Self-reports of
      drug-taking behaviours, service contact, sexual behaviour and HIV knowledge, and
      anonymous testing of saliva for HIV antibodies. FINDINGS: Only 18% had injected
      at least daily. Thirty-five per cent had accepted or passed on used equipment.
      Eighty-five per cent of subjects recruited from non-treatment sites were
      receiving treatment for their drug taking. Multivariate analyses indicated that
      risky injecting was associated with a consistent history of sharing, polydrug
      injecting, injecting in prison, having recently started injecting, and recent
      experience of methadone detoxification. CONCLUSIONS: Injecting frequency and
      equipment sharing have declined substantially in Edinburgh during the past 10
      years and are low compared to other cities in the United Kingdom and elsewhere.
      These improvements have occurred in the context of remarkably high levels of drug
      treatment service contact. Our findings support the international evidence
      indicating that IDUs have modified their injecting habits significantly without
      completely eliminating this form of HIV risk. High levels of service contact in
      Edinburgh provide ample opportunities to instigate further HIV prevention
      measures which target identifiable subgroups of IDUs who persist in risky
      injecting.

PMID- 9624727
TI  - Clinical experience with antagonist-induced opiate withdrawal under anaesthesia.
AB  - AIMS: The study describes experience with antagonist-induced opiate withdrawal
      under anaesthesia in standard clinical conditions. DESIGN: The study was
      restricted to patients who had undergone failed withdrawal treatments with usual
      methods over the past months. No control group was used. SETTING AND PROCEDURE:
      The patients were selected after history-taking and examination. A multi-axial
      diagnosis was performed. They were then admitted to an inpatient treatment unit
      for addicted patients. On the second day they were put into neurological
      intensive care. There they were intubated, ventilated and anaesthetized with
      propofol for 6 hours. Shortly after induction of anaesthesia, naloxone and
      naltrexone were administered. A high amount of fluid was used to balance changes
      in water and electrolytes. After anaesthesia the patients were transferred back
      to the addiction ward and sedated with clonidine. The patients were then fully
      mobilized. On discharge 50 mg naltrexone were given daily. PARTICIPANTS: Eighty
      eight patients were treated. They were long-term opiate users. Preference was
      given to methadone-substituted patients who were unable to rid themselves of
      methadone. MEASUREMENTS: The account given is based solely on clinical
      observations. FINDINGS: The first 14 patients were observed in detail and it is
      on them that this report is based. It was found that withdrawal from codeine and
      methadone can be shortened to approximately 2-3 days. No patient was in a
      condition to go home immediately after anaesthesia. Twelve patients showed
      significant symptoms on the day following anaesthesia. The majority of patients
      treated by this method will continue to suffer withdrawal symptoms for a few days
      after detoxification, after which time most can be treated in an outpatient
      setting. Dysfunction of the cardiovascular system, the lungs, the kidneys or
      other organs was not observed. Taking into account all the 88 patients, five had
      to stay in hospital for a longer period (up to 2 weeks) because of a prolonged
      withdrawal syndrome.

PMID- 9624728
TI  - Beyond stages of change: the quitting continuum measures progress towards
      successful smoking cessation.
AB  - OBJECTIVE: To extend the quitting continuum to categorize smokers in the early
      stages of the process of smoking cessation. DESIGN: A prospective computer
      assisted telephone interview study with initial interviews in 1990 and
      reinterviews in 1992. SETTING AND PARTICIPANTS: In California, 2514 current
      smokers and quitters of less than 5 years duration, selected randomly from a
      large scale cross-sectional survey in 1990. RESULTS: We focus on smokers with
      high addiction (> or = 15 cigarettes/day) and without a strong quitting history
      (> or = 1 week in last year or > or = 1 year ever) at baseline (N = 822). Having
      an intention to quit and a limited quitting history (1-6 days in last year) was
      predictive of progress at follow-up into higher continuum levels ultimately
      associated with successful cessation. Furthermore, smokers with one trait were
      much more likely to progress than those with none. Accordingly, the lowest level
      of the earlier continuum was further subdivided into three subgroups (making
      eight levels overall). Over approximately a 2-year period, most smokers either
      progressed or regressed only one or two levels along the quitting continuum.
      CONCLUSIONS: Better than expected progress along this expanded quitting continuum
      could be a criterion for a successful intervention. Tailored interventions that
      move smokers to a higher level on the continuum should be a priority for future
      research.

PMID- 9624729
TI  - The price of crack in Sao Paulo, Brazil.

PMID- 9624730
TI  - Laboratory diagnosis of plague.
AB  - In response to an outbreak of a plague-like disease in India, the Public Health
      Laboratory Service (PHLS) in the UK distributed advice on the isolation and
      identification of Yersinia pestis. Some of the procedures outlined were evaluated
      using a number of isolates of Y. pestis, complemented with in-house techniques
      detecting virulence genes or their products. These laboratory investigations are
      limited in that they are either only indicative or they take too long (48 hours
      or more), and thus represent a serious delay to the patient. Successful patient
      management must be based on a case history, and therapy should be started
      immediately. Laboratory diagnosis will subsequently rule out most pathogens which
      cause similar infections, yet will still require confirmation by a reference
      laboratory.

PMID- 9624731
TI  - Evaluation of CHROMagar Candida medium for the isolation and direct
      identification of yeast species from the female genital tract.
AB  - The performance and cost-effectiveness of CHROMagar Candida in the isolation and
      identification of Candida species from female genital tract specimens were
      investigated. Eight hundred and forty-three specimens were inoculated in parallel
      onto malt extract agar and CHROMagar Candida. Yeasts isolated on CHROMagar were
      provisionally identified by morphology and pigmentation. Those isolated on malt
      extract agar were further identified by a germ tube test, and negative isolates
      were identified biochemically. A cost comparison was performed, detailing labour
      and material costs. Of 119 yeast isolates, seven were detected only on CHROMagar.
      Mixed Candida spp. from three specimens were only differentiated on CHROMagar.
      There was a 100% correlation between the results of the germ tube test and
      provisional identity on CHROMagar. CHROMagar Candida facilitated the presumptive
      identification of yeast isolates from the female genital tract, and the detection
      of mixed populations. The cost of the media was higher than malt extract agar and
      germ tube testing, but the rapid identification of isolates to species level and
      ease of use may be of sufficient advantage to justify the extra cost.

PMID- 9624732
TI  - Evidence for the anti-hyperlipidaemic activity of the edible fungus Pleurotus
      ostreatus.
AB  - The effects are described of adding either the dried fruiting bodies of the
      oyster fungus Pleurotus ostreatus, or an ethanolic extract of it, to the diet of
      normal Wistar male rats and a strain with hereditary hypercholesterolaemia.
      Addition of the dry oyster fungus to the diet significantly increased, by more
      than two-fold, the triacylglycerol (TAG) level in the plasma of both groups of
      rats compared with their respective controls. In contrast, the ethanolic extract
      did not significantly change TAG levels. Values for total cholesterol and its
      high- and low-density lipoprotein fractions in the plasma, as well as the
      calculated atherogenic index, did not show any significant change. Levels of
      liver cholesterol were significantly lowered by the dried oyster fungus in both
      hypercholesterolaemic and normal groups of rats, and by the ethanolic extract in
      normal rats. A significantly increased phospholipid-to-cholesterol ratio in the
      aortas of both groups of rats, after the administration of either dried oyster
      fungus or the ethanolic extract of it, suggests a favourable anti-atherogenic
      effect for both.

PMID- 9624733
TI  - Monocyte analysis in chronic myelomonocytic leukaemia.
AB  - It is suggested that monocytes in patients with chronic myelomonocytic leukaemia
      (CMML) or chronic myeloid leukaemia (CML) with monocytosis have
      morphological/functional abnormalities which cause inaccurate counting in
      automated analysers. In this study, monocytes in 21 normal and 14 CMML blood
      samples were subjected to morphological analysis and were counted by the manual
      reference method, three automated analysers and esterase staining. Morphological
      analysis showed no significant difference between control and CMML monocytes. The
      alpha-naphthyl acetate esterase scores, a measure of monocyte function, showed a
      reduction of 40% in CMML monocytes compared to controls. Counts by analysers
      showed that the Sysmex NE 8000 was the least accurate for CMML monocyte counts
      and that the Coulter STK-S and Sysmex SE 9000 gave results closer to the manually
      counted standards.

PMID- 9624734
TI  - Immune stimulation by syphilis and malaria in HIV-2-infected and uninfected
      villagers in West Africa.
AB  - Co-infections such as Mycobacterium tuberculosis (TB) and Pneumocystis pneumonia
      may affect the progress of HIV infection and speed the onset of death. As malaria
      and syphilis are both endemic in West Africa we examined their effects on HIV-2
      infection, for these may also accelerate the progress of disease. A community
      based case-control study was undertaken in a rural village in Guinea-Bissau, West
      Africa. One hundred and fifty asymptomatic subjects seropositive for HIV-2 and
      154 age- and sex-matched controls were enrolled. Venous blood samples taken into
      EDTA were stained within six hours of collection with CD4 and CD8 monoclonal
      antibodies and processed by Q-Prep machine in the field. The stained cells were
      then transported on ice by road and analysed by FACS-can at the base laboratory
      in The Gambia within a week. The mean CD4% was significantly lower and geometric
      mean neopterin and beta 2-microglobulin levels were significantly higher in the
      HIV-2-infected subjects than in the controls (P < 0.01 for all cases versus all
      controls). The mean CD4% was lower and beta 2-microglobulin level was higher in
      both HIV-2 and control subjects with active or past syphilis when compared with
      subjects with no syphilis; however, syphilis did not have a marked effect on
      plasma neopterin level. Malaria infection raised neopterin levels, but had little
      effect on CD4%. Overall multiple regression analysis allowing for HIV-2 infection
      and other variables showed that syphilis lowered CD4% (P = 0.01) and raised beta
      2-microglobulin levels (P = 0.05) and malaria raised neopterin levels (P = 0.05).
      The conclusions are that HIV-2 infection is associated with lower CD4% and higher
      neopterin and beta 2-microglobulin levels than controls, and co-infection with
      syphilis is associated with a further lowering of CD4%, suggesting a worse
      suppression of the immune system. Co-infection with malaria is associated with a
      modest immune disturbance.

PMID- 9624735
TI  - The use of immunochromatography test cards in the diagnosis of hepatitis B
      surface antigen among pregnant women in West Africa.
AB  - Despite the development of successful vaccines against hepatitis B virus (HBV),
      Sierra Leone, like many countries lying within the geographical region where HBV
      infection is highly endemic, has yet to implement an immunisation or mass
      screening programme. However, certain sectors of the population could benefit
      from HBV screening if it was readily available and affordable. The use of a newly
      introduced immunochromatography (IC) test card for hepatitis B surface antigen
      (HBsAg) is examined for use among an ante-natal population in Sierra Leone, and
      compared with the existing reverse passive haemagglutination (R-PHA) method. The
      prevalence of HBsAg and hepatitis B envelope antigen (HBeAg) in the study
      population (n = 179) was 11.3% and 3.9%, respectively. The speed, sensitivity and
      simplicity of the IC method make it attractive, particularly for individual use
      and where laboratory facilities are minimal, but the cost of the test is
      comparatively high. In the African setting, pending the introduction of HBV
      vaccination into the Expanded Programme on Immunisation (EPI), the IC test card
      may be of use in the private sector where the turnover of patients is small, as a
      rapid means of detecting HBsAg in pregnant women who can afford both this
      facility and HBV vaccination of their newborn babies.

PMID- 9624736
TI  - Polymorphonuclear neutrophils in saliva and blood: a comparative study of
      morphology, function and phenotype.
AB  - The morphology, phagocytic activity, production of hydrogen peroxide (H2O2) and
      expression of lymphocyte function-associated antigen-1 (LFA-1; CD11a/CD18),
      complement receptor type 3 (CR3; CD11b/CD18), p150,95 (CD11c/CD18), and
      platelet/endothelial cell adhesion molecule-1 (PECAM-1; CD31) by oral
      polymorphonuclear neutrophils (PMN) are assessed and the results compared with
      those of blood PMN. There were no differences in the morphology and phagocytic
      activity between oral and blood PMN. H2O2 production was measured following
      stimulation with phorbol myristate acetate (PMA) and N-formyl-L-leucyl-L
      phenylalanine (FMLP) as indicators of bactericidal activity. There was a
      significant difference in the H2O2 production by the two groups when stimulated
      with FMLP; the level of H2O2 production by oral PMN was significantly higher than
      that by blood PMN. However, there was no significant difference in H2O2
      production between oral and blood PMN when stimulated with PMA. The percentage of
      CD11a- and CD11c-positive concentrated oral PMN was significantly lower than that
      seen in blood PMN, as was the percentage of CD31-positive cells. Higher H2O2
      production by oral PMN following stimulation with FMLP may result in enhanced
      bactericidal activity. Low expression of CD31 may lead to the accumulation of PMN
      in the mouth by blocking their return to the bloodstream. These phenomena may be
      necessary for oral PMN to protect periodontal tissues from bacteria in the mouth.

PMID- 9624737
TI  - Mutagen sensitivity in thymidine kinase- and methyltransferase-deficient human
      lymphoblastoid cells.
AB  - In this study, the effect of thymidine kinase deficiency on the responses of the
      human lymphoblastoid cell line Raji to methyl methanesulphonate and mitomycin C
      was investigated. Mutagen sensitivity was measured in terms of cell survival and
      mutation to hypoxanthine-guanine phosphoribosyltransferase deficiency. Thymidine
      kinase-deficient Raji cells showed decreased survival and increased mutant
      frequency relative to wild-type cells following treatments with each of the
      mutagens used. It is suggested that this may be due to an imbalance in the supply
      of deoxyribonucleoside triphosphates to the excision repair process. The role of
      O6-methylguanine-DNA methyltransferase in the repair of DNA damage caused by
      these mutagens is also discussed.

PMID- 9624738
TI  - Adenovirus-associated gastro-enteritis in the north-west of England: 1991-1994.
AB  - Faeces, positive for adenoviruses by electron microscopy on initial examination
      at Manchester Public Health Laboratory (PHL) or Preston PHL during the period
      1991-1994, were examined by an enzyme immunoassay which differentiated Ad40, Ad41
      and non-AdF strains. Isolation and serotyping by neutralisation of non-AdF
      strains were attempted in PLC/PRF/5 cells. Of 452 specimens examined, 99 (22%)
      contained Ad40, 209 (46%) Ad41 and 144 (32%) non-AdF serotypes. From 1991 to 1993
      the ratio of Ad40 to Ad41 was constant at approximately 1 to 1.6, but in 1994 it
      was almost 1 to 5. Non-AdF serotypes, of which Ad1 and Ad2 were the most common,
      accounted for 44% of specimens tested from 1991, but this dropped to 20% of those
      from 1994. An age/sex analysis showed that half the specimens examined were from
      infants under one year old, and that overall the male/female ratio was 3 to 2.
      The significance of these results is discussed, including the changing prevalence
      of Ad40 and Ad41, and the role of non-AdF serotypes in gastro-enteritis.

PMID- 9624739
TI  - Use of immunodeficient mice in metastasis research.
AB  - One of the major clinical problems facing the western world is how to stem the
      tide of deaths from metastasising malignancies. Despite some progress in
      diagnosis and treatment, the death rate from major clinically important tumours,
      such as lung, breast and colon cancer, shows no signs of abating. This
      therapeutic failure is due to tumour metastasis, for which no treatment options
      are available. Effort has been made to find valid animal models in which the
      metastatic process can be studied, and in which putative treatments can be
      evaluated. This review discusses some of the approaches used in creating these
      models, and focuses on current work using the severe combined immunodeficient
      (SCID) mouse.

PMID- 9624740
TI  - Lupus anticoagulants: pathogenesis and laboratory diagnosis.
AB  - The pathogenesis of the lupus anticoagulant (LA) has been the focus of much
      research over the past decade, and a plethora of laboratory tests have been
      developed to detect it. This essay reviews the nature of LA and its pathogenesis,
      and a number of approaches employed in its diagnosis. These range from well
      established tests such as the kaolin clotting time (KCT), activated partial
      thromboplastin time (APTT) and tissue thromboplastin inhibition test (TTI), to
      the 'newer' tests such as the dilute Russell's viper venom time (DRVVT) and more
      recent snake venom tests such as the textarin/ecarin ratio and Taipan snake venom
      time (TSVT). The criteria for diagnosis are discussed, including pre-analytical
      variables such as sample preparation, and the effects of therapeutic
      anticoagulants used to treat thrombotic manifestations of the syndrome or an
      underlying disease process.

PMID- 9624741
TI  - Human papillomavirus: disease and laboratory diagnosis.
AB  - Human papillomaviruses (HPVs) can be classified biologically or phylogenetically
      into cutaneous or mucosal types. Cutaneous papillomaviruses produce benign skin
      tumours (warts) which occur commonly on the hands, face and feet. They spread
      readily among children and young adults during recreational activities.
      Laboratory diagnosis of skin warts is usually unnecessary as they can be
      distinguished morphologically. Large numbers of cutaneous warts may develop in
      patients with epidermodysplasia verruciformis, a rare familial disorder. Exposure
      to sunlight sometimes causes these lesions to progress to skin cancer. HPVs are
      the most common sexually transmitted viruses, infecting both men and women. They
      can be transmitted from the vagina at birth, and may cause recurrent respiratory
      papillomas in childhood or adult life. Genital infection usually clears within a
      few months, but may persist in some individuals. HPV has been firmly linked with
      cancer of the cervix, and is also associated with cancer at other mucosal sites.
      The distribution of genital HPV types varies and is related to the degree of
      cervical dysplasia present. HPV types 6 and 11 are frequently found in sexually
      active adults, and are associated with low-grade squamous epithelial lesions. HPV
      types 16, 18, 31 and 45 are found less frequently, and are associated with
      progression to invasive cancer. Commercial dot blot hybridisation and DNA-RNA
      hybridcapture assays are available for laboratory diagnosis of genital HPV
      infection. The polymerase chain reaction (PCR) is used for diagnosis and
      epidemiological surveys. Detection of particular HPV types could be useful in the
      diagnosis and management of cervical cancer in older women, and for resolving
      equivocal (borderline) cytology. HPV assays, which can distinguish between high
      grade and low-grade disease, may also have a role in routine cervical screening.

PMID- 9624742
TI  - Community hospitals: new wine in old bottles?

PMID- 9624743
TI  - Shifting the work.

PMID- 9624745
TI  - Evaluation of a primary care counselling service in Dorset.
AB  - BACKGROUND: Research into the effectiveness of counselling in primary care is
      rare. This study attempts to provide a thorough evaluation of the effects of a
      new counselling service introduced throughout Dorset. AIM: To evaluate the impact
      of counselling on client symptomatology, self-esteem, and quality of life. The
      effect of counselling on drug prescribing, referrals to other mental health
      professionals, and client and general practitioner (GP) satisfaction were also
      assessed. METHOD: All new clients referred for counselling were asked to complete
      and return questionnaires before and after counselling. A total of 385 clients
      took part in the study. The first and second assessments were compared
      statistically. Clients were ascribed a psychiatric diagnosis using a simplified
      version of DSM-IIIR (Diagnostic and Statistical Manual of the American
      Psychiatric Association). GPs' views of the service were determined using a
      specially designed questionnaire. Drug data were obtained from the Prescription
      Pricing Authority and referral statistics from Dorset HealthCare National Health
      Service (NHS) Trust. RESULTS: The number of psychiatric symptoms and their
      severity were significantly reduced by counselling. There were no significant
      differences in the prescription of anxiolytic/hypnotic and anti-depressant
      medication between matched practices with and without counsellors. The presence
      of a counsellor did not affect the rate of referral to other mental health
      professionals. Clients and GPs valued the service highly. CONCLUSIONS: The
      Psychology Managed Counselling Service is an effective method of running a
      counselling service and is well received by both clients and GPs. Counselled
      clients improved significantly on several measures.

PMID- 9624744
TI  - A randomized controlled trial and economic evaluation of counselling in primary
      care.
AB  - BACKGROUND: Counselling in primary care settings remains largely unevaluated.
      Such evaluation has been strongly recommended. AIM: To determine the relative
      effectiveness and cost-effectiveness of generic counselling and usual general
      practitioner (GP) care for patients with minor mental health problems. METHOD: A
      randomized controlled trial and health economic evaluation were carried out in
      nine general practices. Access to generic counselling (brief counselling,
      generally involving up to six 50-minute sessions) was compared with usual GP
      care. A total of 162 patients aged 16 years and over with diverse mental health
      problems (excluding phobic conditions and psychoses) were randomized. The
      Hospital Anxiety and Depression (HAD) scale, COOP/WONCA (World Organization of
      Family Doctors) functional health assessment charts, and the delighted-terrible
      faces scale were used to assess outcome four months after randomization. RESULTS:
      The two groups were similar at baseline. There were significant improvements in
      both groups between randomization and follow-up for most outcome measures, but no
      significant differences between the study arms. The 95% confidence limits were
      narrow and excluded clinically significant effects. Under various assumptions
      concerning the cost of secondary care referrals and of counselling time, no clear
      cost advantage was associated with either intervention. CONCLUSIONS: This
      pragmatic trial demonstrates no difference in functional or mental health outcome
      at four months between subjects offered access to counselling and those given
      usual care by their GP. There is no clear difference in the cost-effectiveness of
      the two interventions. Purchasers should take account of these findings in
      allocating resources within primary care.

PMID- 9624746
TI  - Relationship between practice organization and cardiovascular risk factor
      recording in general practice.
AB  - BACKGROUND: Research findings suggest that the level of cardiovascular risk
      factor recording in general practice is not yet optimal. Several studies indicate
      a relation between the organization of cardiovascular disease prevention at
      practice level and cardiovascular risk factor recording. AIM: To explore the
      relation between the organization of cardiovascular disease prevention and risk
      factor recording in general practice. METHOD: A cross-sectional study was
      conducted using data on adherence to selected practice guidelines and on
      cardiovascular risk factor recording from 95 general practices. Practice
      guidelines were developed beforehand in a consensus procedure. Adherence was
      assessed by means of a questionnaire and practice observations. Risk factor
      recording was assessed by an audit of 50 medical records per practice. RESULTS:
      Factor analysis of risk factor recording revealed three dimensions explaining 76%
      of the variance: recording of health-related behaviour, recording of clinical
      parameters, and recording of medical background parameters. Adherence to the
      guideline 'proactively invite patients to attend for assessment of cardiovascular
      risk' was related to a higher recording level in all three dimensions. Practice
      characteristics did not show a consistent relationship to the level of risk
      factor recording. CONCLUSION: This study indicates that the presence of a system
      of proactive invitation was related to the recording of cardiovascular risk
      factors in medical records in general practice.

PMID- 9624747
TI  - A survey of job satisfaction, sources of stress and psychological symptoms among
      general practitioners in Leeds.
AB  - BACKGROUND: The past seven years have seen rapid changes in general practice in
      the United Kingdom (UK), commencing with the 1990 contract. During the same
      period, concern about the health and morale of general practitioners (GPs) has
      increased and a recruitment crisis has developed. AIM: To determine levels of
      psychological symptoms, job satisfaction, and subjective ill health in GPs and
      their relationship to practice characteristics, and to compare levels of job
      satisfaction since the introduction of the 1990 GP contract with those found
      before 1990. METHOD: Postal questionnaire survey of all GP principals on the
      Leeds Health Authority list. The main outcome measures included quantitative
      measures of practice characteristics, job satisfaction, mental health (General
      Health Questionnaire), and general physical health. Qualitative statements about
      work conditions, job satisfaction, and mental health were collected. RESULTS: A
      total of 285/406 GPs (70%) returned the questionnaires. One hundred and forty
      eight (52%) scored 3 or more on the General Health Questionnaire (GHQ-12), which
      indicates a high level of psychological symptoms. One hundred and sixty GPs (56%)
      felt that work had affected their recent physical health. Significant
      associations were found between GHQ-12 scores, total job satisfaction scores, and
      GPs' perceptions that work had affected their physical health. Problems with
      physical and mental health were associated with several aspects of workload,
      including list size, number of sessions worked per week, amount of time spent on
      call, and use of deputizing services. In the qualitative part of the survey, GPs
      reported overwork and excessive hours, paperwork and administration, recent
      National Health Service (NHS) changes, and the 1990 GP contract as the most
      stressful aspects of their work. CONCLUSIONS: Fifty-two per cent of GPs in Leeds
      who responded showed high levels of psychological symptoms. Job satisfaction was
      lower than in a national survey conducted in 1987, and GPs expressed the least
      satisfaction with their hours, recognition for their work, and rates of pay.
      Nearly 60% felt that their physical health had been affected by their work. These
      results point to a need to improve working conditions in primary care and for
      further research to determine the effect of any such changes.

PMID- 9624748
TI  - Postnatal depression in the community.
AB  - BACKGROUND: Postnatal depression affects 15% of all women derived. Good practice
      in antenatal and postnatal care suggests that regular contact should take place
      with members of the primary health care team (PHCT) but, despite this, many cases
      of postnatal depression are probably not detected. It is also widely perceived
      that depressed women consult more frequently about themselves and their babies,
      but it is not clear whether the number of contacts with the primary health care
      team as a whole reflects this. AIM: To determine whether the use of the Edinburgh
      Postnatal Depression Scale (EPNDS) at postnatal examination would detect women
      not recognized as depressed by the PHCT. To determine whether the number of
      contacts with the PHCT could be used as a screening tool for postnatal
      depression. METHOD: The EPNDS was administered at postnatal examination to 176
      women delivering their babies between 1 April 1995 and 31 October 1995. Contacts
      with PHCT members were recorded up to the 42nd day after delivery, together with
      their assessment of the subjects' mental health. RESULTS: Of 30 women scoring >
      or = 12 on the EPNDS, only 13 were perceived to be depressed by the PHCT. The
      team as a whole identified more depressed women than any individual professional
      group. There was no significant difference in the number of contacts made with
      professionals by women who were or were not depressed. Asian women were more
      likely to be depressed than women from other ethnic groups. CONCLUSION: Despite
      the PHCT as a whole identifying more depressed women than any individual group,
      more than half were not identified by professionals. Tools such as the EPNDS
      should be used routinely in primary care; there is an urgent need to validate the
      EPNDS for non-Caucasian women.

PMID- 9624749
TI  - 'So much post, so busy with practice--so, no time!': a telephone survey of
      general practitioners' reasons for not participating in postal questionnaire
      surveys.
AB  - BACKGROUND: Response rates by general practitioners (GPs) to postal surveys have
      consistently fallen, compromising the validity of this type of research. If
      postal survey work is to continue we need to understand GPs' reasons for not
      participating and respond appropriately. AIM: To investigate GPs' reasons for not
      responding to postal surveys. METHOD: A qualitative study was carried out to
      determine GPs reasons for not participating in postal surveys, which were drawn
      from a telephone survey of 276 non-responders to a postal questionnaire survey.
      Practitioners' comments were recorded and reasons for their non-response
      quantified using content analysis. RESULTS: Primary reasons for GPs not replying
      to the postal survey were that questionnaires had got lost in paperwork (34%),
      that GPs were too busy for the extra work involved (21%), and that questionnaires
      were routinely 'binned' (16%). Higher practice workloads, including increased
      administration, meant that participation in research had become a low priority.
      GPs provided some suggestions for researchers that would increase their chances
      of questionnaires being returned. CONCLUSIONS: Researchers need to be aware of
      the pressures of service general practice and to rationalize the amount of
      research material sent to GPs. GPs were most likely to respond to postal surveys
      that had a high interest factor, that involved localized research relevant to
      general practice, and that incorporated a personalized approach by researchers,
      including good-quality explanatory information.

PMID- 9624750
TI  - General practitioner turnover and migration in England 1990-94.
AB  - BACKGROUND: In tandem with fears about a GP workforce crisis, increasing
      attention is being focused on the supply and distribution of primary care
      services: on general practitioners in particular. Differential turnover and
      migration across health authority boundaries could lead to a maldistribution of
      GPs, yet comprehensive studies of GP turnover are non-existent. AIM: To quantify
      general practitioner (GP) turnover and migration in England from 1990 to 1994.
      METHOD: Yearly data from 1 October 1990 to 1 October 1994 were collected on GPs
      in England practising full time, including average yearly turnover, rates of
      entry to and exit from general practice, and net migration among GPs. All were
      calculated at the family health service authority (now the new health
      authorities) level. RESULTS: Average yearly GP turnover ranges from 2.9% in
      Shropshire to 7.8% in Kensington, Chelsea and Westminster; turnover is associated
      with deprivation and high-need areas. Migration of GPs across health authority
      borders was rare. Entry and exit rates were also positively related to measures
      of deprivation and need. Relatively underprovided health authorities lost 23 GPs
      over the study period as a result of migration; relatively overprovided ones
      gained three. CONCLUSION: Turnover is driven primarily by exits from general
      practice and is related to deprivation and high need. Retention appears to be the
      main problem in ensuring an adequate GP supply in relatively deprived and
      underprovided health authorities.

PMID- 9624751
TI  - Is international travel useful for general practitioners? A survey of
      international travel scholarships.
AB  - BACKGROUND: The Royal College of General Practitioners has offered international
      travel scholarships for the past decade. Each year a number of general
      practitioners travel from the UK to work or study assisted by the scheme, while
      others come to this country for similar purposes. AIM: To investigate the value
      of international scholarships for recipients and others. METHOD: All those
      receiving awards in 1988-94 were surveyed by postal questionnaire. RESULTS: Fifty
      one out of 58 award winners (88%) replied. Almost all cited some of a wide
      variety of personal benefits from international travel, and some established
      continuing links with colleagues overseas. Many gave examples of useful results
      for others, both patients and colleagues. Scholarships appear to have made a
      significant contribution to careers, especially for those based outside Britain.
      CONCLUSION: Relatively modest travel scholarships were viewed both favourably in
      hindsight and produced a wide range of benefits to recipients, colleagues, and
      patients. International travel should probably be considered more widely in
      career planning.

PMID- 9624752
TI  - Self-recorded stress levels for general practitioners before and after forming an
      out-of-hours primary care centre.
AB  - The Nottingham Stress-Arousal Checklist (SACL) was used to compare stress and
      arousal levels within a group of 36 Scottish general practitioners (GPs) before
      and after an out-of-hours primary care centre opened in 1995. Overall, GPs
      reported significantly lower stress and higher arousal scores with the new
      service.

PMID- 9624753
TI  - Do GPs have the techniques for 'watchful waiting' in glue ear?
AB  - 'Watchful waiting' for glue ear in children within primary care as a precursor or
      alternative to surgery is one of the increasing pressures on general
      practitioners (GPs) to limit outpatient referrals. An equipment survey questions
      whether primary care is properly equipped to 'watch', given the limited access to
      audiological equipment that might objectively underpin a decision on when
      'waiting' should end.

PMID- 9624754
TI  - Telling the truth: what do general practitioners say to patients with dementia or
      terminal cancer?
AB  - A questionnaire was sent to all general practitioners (GPs) in Cambridgeshire
      asking them about their practice in telling patients with dementia or terminal
      cancer their diagnosis. Although the majority of GPs would always or often tell
      patients of a diagnosis of terminal cancer, this was not the case in dementia;
      uncertainty of diagnosis was cited as the most important factor in not giving the
      diagnosis. The implications of these findings are discussed in the light of the
      GP's role in dementia and the development of new anti-Alzheimer's drugs.

PMID- 9624755
TI  - STD and HIV screening in general practice: a survey related to termination of
      pregnancy in south Thames.
AB  - It has been recommended that screening for sexually transmitted disease (STDs) be
      carried out at the time of termination of pregnancy to allow prevention of post
      abortion infection. Screening offers the opportunity to treat an infected woman
      and prevent serious complications following the termination procedure. Our
      findings indicate that general practitioners (GPs) in South Thames did not
      routinely carry out screening and few realized it took place at referral centres.

PMID- 9624756
TI  - Increased general practice workload due to a primary care led National Health
      Service: the need for evidence to support rhetoric.
AB  - Recent policy initiatives have focused on shifts in the balance of care from
      secondary care to primary care. A consequence of such shifts is increased
      workload in primary care. The aim of this paper is to appraise the literature
      critically to assess whether changes in the balance of care have led to
      additional work for general practices. In particular, the implications of this
      literature for the measurement of workload in general practice are highlighted.
      After an extensive, systematic literature search, only 12 studies that met the
      review criteria were identified. Although the studies pointed to negligible
      effects on the number of general practitioner (GP) visits, they failed to capture
      the many other attributes of a practice's work that are likely to be influenced
      by a shift in the balance of care. These include both qualitative (e.g. stress
      and mental effort) and quantitative (i.e. the use of resources in the practice,
      such as GPs, nurses and other staff's time and administration) measures of
      workload. The studies may therefore have under-estimated the effect on practice
      workload. To identify correctly the impact on workload of shifts in the balance
      of care, studies evaluating shifts need to improve their measurement of general
      practice workload. Furthermore, an extended definition of workload needs to be
      developed and tested, and workload monitored over time.

PMID- 9624757
TI  - Cluster randomization: a trap for the unwary.
AB  - Controlled trials that randomize by practice can provide robust evidence to
      inform patient care. However, compared with randomizing by each individual
      patient, this approach may have substantial implications for sample size
      calculations and the interpretation of results. An increased awareness of these
      effects will improve the quality of research based on randomization by practice.

PMID- 9624758
TI  - Nurse practitioners.

PMID- 9624759
TI  - Nurse practitioners.

PMID- 9624760
TI  - Training in palliative care.

PMID- 9624761
TI  - Is there sufficient evidence for us to encourage the widespread use of hormone
      replacement therapy to prevent disease?

PMID- 9624762
TI  - Medicine and the arts: let's not forget the medicine.

PMID- 9624763
TI  - Hormone replacement therapy: assessment of present use, costs, and trends.
AB  - BACKGROUND: Hormone replacement therapy (HRT) is probably unprecedented as a drug
      in widespread preventive use by a predominantly well population, but there is
      little direct data on current trends in use. AIM: To estimate trends in the use
      and cost of HRT in Britain. METHOD: Government prescription data and therapy cost
      data were analysed to provide trends in costs and point prevalence of the use of
      HRT since 1980. Projections were estimated to the year 2000. RESULTS: In 1987,
      HRT was used by an estimated 2.2% of women aged 40 to 64 years in England, and by
      1.0% in Scotland. By 1994 this had risen to 21.7% in England, 20.4% in Scotland,
      and 21.3% in Wales. Between 1980 and 1986, costs remained steady at approximately
      11 million Pounds per annum for England and 1 million Pounds for Scotland (1994
      values). Between 1987 and 1994 they rose to 87 million Pounds for England, 10
      million Pounds for Scotland, and 46 million Pounds for Wales (1994 values).
      Projections suggest that, by the year 2000, 25.4% of women aged 40 to 64 years
      (95% CI = 20.1-30.7%) will be taking HRT at any one time, at a cost of 150
      million Pounds (95% CI = 142 m Pounds-157 m Pounds: 1994 values). This implies an
      'ever' user prevalence of at least two-thirds of women in this age group.
      CONCLUSION: Use of HRT for long-term therapy is widespread and rising. It is
      estimated that prevalence has increased tenfold since 1987. Average individual
      costs of therapy have fallen by one third. The level of reduced risk of
      osteoporosis and cardiovascular disease, and the balance with cost and potential
      increased risk of breast cancer, are not yet established and are in need of
      clarification.

PMID- 9624764
TI  - Towards a better diagnosis of throat infections (with group A beta-haemolytic
      streptococcus) in general practice.
AB  - BACKGROUND: Sore throat is a common complaint in general practice. However,
      management strategies are not very clear. A better diagnostic procedure is needed
      to prevent the overuse of antibiotics. AIM: To assess the diagnostic value of a
      rapid streptococcal antigen detection test in addition to four clinical features
      in patients with sore throat, using throat culture and antibody titres as
      reference tests. METHOD: Four clinical features [fever (history) > or = 38.0
      degrees C, lack of cough, tonsillar exudate, and anterior cervical
      lymphadenopathy] were registered in 558 patients aged 4 to 60 years presenting
      with sore throat of no more than 14 days' duration. A rapid diagnostic test was
      performed, as well as a throat culture and antibody titres [fourfold increase in
      anti-streptolysin-O (ASO) and/or anti-deoxyribonuclease B (anti-DNAase B)] in
      patients aged 11 years and older. RESULTS: Throat cultures were positive for
      group A beta-haemolytic streptococcus (GABHS) in 33% of the patients. Rapid tests
      were positive in 24%. Compared with the throat culture, the sensitivity of the
      rapid test was 65%, the specificity 96%, the positive predictive value 88%, and
      the negative predictive value 85%. However, for patients with three or four
      clinical features, the sensitivity of the rapid test was considerably higher at
      75%. Children (< or = 14 years) had a slightly raised specificity and raised
      positive predictive value and prevalence. With the antibody titres as a
      reference, the rapid test performed as well as the throat culture with regard to
      its predictive value. CONCLUSION: For the management of patients with sore throat
      in general practice, a rapid test may have an additional value, especially in
      patients with a high chance of having GABHS infection. However, as the
      sensitivity of the test studied is low, tests with a higher sensitivity are
      needed.

PMID- 9624765
TI  - Preconception care: who needs it, who wants it, and how should it be provided?
AB  - BACKGROUND: Preconception care (PC) aims to identify and reduce a number of
      modifiable factors that can adversely affect pregnancy outcome. AIM: To ascertain
      both knowledge of the attitudes towards PC among members of primary health care
      teams (PHCTs) and registered women of childbearing age in a representative sample
      of general practices in Harrow. METHOD: A questionnaire survey was conducted in a
      randomly selected group of nine general practices in the London borough of
      Harrow. Subjects included all relevant health professionals and female patients
      of childbearing age registered with the practices. RESULTS: A total of 62/88
      (70.5%) health professionals and 811 women (1 in 20 of the entire target
      population) completed the questionnaires. Nurses' knowledge matched that of the
      doctors, except in the area of genetics. Over 85% of all health professionals
      believed that PC could be of benefit to both mother and baby. Women were
      generally well informed; Asian women, those born outside the UK, those who had
      never been pregnant, and those who had not undertaken education beyond the age of
      18 years were significantly less well informed. Health professionals considered
      PC to be best delivered opportunistically by nurses, and this method appeared to
      be acceptable to most female patients of childbearing age, although it was
      significantly less acceptable among Asians. CONCLUSION: Among health
      professionals and women of childbearing age, there is generally a good level of
      knowledge of PC, although certain groups are less well informed than others and
      could benefit from a targeted education approach. Widespread agreement that PC is
      worthwhile was found among PHCT members, but this view is less strongly held by
      the female public, with the acceptability of providing PC opportunistically
      differing significantly between ethnic groups.

PMID- 9624766
TI  - Intensive cardiovascular risk factor intervention in a rural practice: a glimmer
      of hope?
AB  - BACKGROUND: Large trials of primary care-based health promotion to modify
      coronary heart disease risks have shown only modest benefits. Could more
      intensive intervention, with doctors sharing with practice nurses in health
      promotion, produce better health outcomes in the context of the small family
      practice? How cost-effective might these interventions be? AIM: To assess the
      cost-effectiveness of an intensive programme of coronary heart disease (CHD) risk
      factor modification in a rural general practice in which doctors had a major
      input. METHOD: A longitudinal study of changes in risk factors in a group of
      adult patients identified as having one or more major CHD risk factor and
      monitored for one to seven years. Patients were recruited from and followed up in
      health promotion clinics, routine practice nurse appointments, or routine
      doctors' surgeries. All received the practice's routine interventions to modify
      risk, and changes in risk factors were recorded. Time spent by members of the
      primary health care team on CHD health promotion was recorded over a two-year
      period. RESULTS: From a practice list of 2040, 760 patients with one or more CHD
      risk factors were identified and followed up over a mean of 3.61 years (range six
      months to seven years). Significant improvements in each of the risk factors
      occurred, except in body mass index (BMI). Mean Dundee risk scores fell from 7.4
      to 5.7 (by 23.3%). The annual cost to the practice (including
      doctor/nurse/secretarial time plus sundry practice expenses and laboratory costs,
      but excluding drug costs) was 6000 pounds. Cost per coronary death prevented was
      calculated as approximately 10,000 pounds. CONCLUSION: The results show an effect
      on risk factors broadly similar but slightly greater in magnitude than that
      achieved in the OXCHECK and British Family Heart Studies of nurse-delivered risk
      factor intervention in primary care. The results suggest that more intensive
      effort in lifestyle modification and health promotion, with more active
      involvement of doctors, could produce significant additional benefit. The cost
      effectiveness of this approach compares favourably with many other accepted
      measures in coronary heart disease prevention.

PMID- 9624767
TI  - Comparison of video-recorded consultations with those in which patients' consent
      is withheld.
AB  - BACKGROUND: Video-recorded consultations are widely used for research in general
      practice. Recently, video recordings have begun to be used for the purposes of
      general practitioner (GP) registrar assessment. It is unknown, however, whether
      consultations in which patients withhold consent for recording differ from those
      that are recorded. AIM: To compare clinical problems and demographic
      characteristics of adult patients who consent to the video recording of
      consultations with those who withhold consent. METHOD: This was prospective study
      of 538 adult patients consulting 42 GPs, based in practices throughout
      Leicestershire. Each patient attended a surgery session with one of the 42 GPs
      between April 1995 and March 1996. Clinical presentations and demographic
      characteristics of patients consenting and withholding consent to the video
      recording of their consultations were compared. GPs' perceptions of whether
      patients in these two groups were distressed/upset or embarrassed were also
      compared. RESULTS: A total of 85.9% (462/538) of adults consented to video
      recording, and 14.1% (76/538) withheld consent. Multiple logistic regression
      revealed that patients who presented with a mental health problem were more
      likely to withhold consent to recording (odds ratio 2.5, 95% confidence interval
      1.4-4.6). Younger patients were also more likely to withhold consent to video
      recording. Additionally, where patients' consent was withheld, GPs perceived
      patients to be more distressed or embarrassed. CONCLUSION: Younger patients and
      those suffering from mental health problems are more likely than others to
      withhold consent to being video recorded for research purposes in general
      practice. The implications of this study for the assessment of registrar GPs
      using video-recorded consultations are discussed.

PMID- 9624768
TI  - General practitioners and women with urinary incontinence.
AB  - BACKGROUND: Urinary incontinence is a common problem for adult women. It results
      in a large financial and psychosocial cost. Much urinary incontinence goes
      unreported. Women with urinary incontinence can be successfully assessed and
      treated in general practice but studies have shown that many GPs manage the
      condition inadequately. AIM: This study aims to examine GPs' awareness of urinary
      incontinence in women and their management of, and attitudes to, female urinary
      incontinence. METHOD: A qualitative study was conducted with 21 GPs responding to
      semi-structured interviews. Thematic analysis was carried out on these
      interviews, with recurrent views and experiences being identified and grouped.
      RESULTS: The interviews of 11 male and nine female GPs were suitable for
      analysis. GPs were aware of the prevalence and under-reporting of urinary
      incontinence in women. Many were unhappy with their own management of the
      condition and with the management options available to them. Male GPs in
      particular were reluctant to carry out gynaecological examinations, and few GPs
      expressed enthusiasm for teaching pelvic floor exercises or bladder drills.
      Medications were frequently used but generally considered ineffective or
      intolerable. The services of both public health nurses and practice nurses were
      under-used, largely because of lack of training in this area. Although
      incontinence nurses were employed in the area, many GPs did not know of their
      availability and, of those who did, few referred to them more than infrequently.
      CONCLUSION: This study demonstrates that many GPs avoid dealing with the problem
      of urinary incontinence in women and that they find it to be a difficult, chronic
      problem to treat. Specialist options seem not to be useful in general practice.
      The findings need to be explored in other GP settings.

PMID- 9624769
TI  - A survey of audit activity in general practice.
AB  - BACKGROUND: Since 1991, all general practices have been encouraged to undertake
      clinical audit. Audit groups report that participation is high, and some local
      surveys have been undertaken, but no detailed national survey has been reported.
      AIM: To determine audit activities in general practices and the perceptions of
      general practitioners (GPs) regarding the future of clinical audit in primary
      care. METHOD: A questionnaire on audit activities was sent to 707 practices from
      18 medical audit advisory group areas. The audit groups had been ranked by annual
      funding from 1992 to 1995. Six groups were selected at random from the top,
      middle, and lowest thirds of this rank order. RESULTS: A total of 428 (60.5%)
      usable responses were received. Overall, 346 (85%) responders reported 125.7
      audits from the previous year with a median of three audits per practice. There
      was no correlation between the number of audits reported and the funding per GP
      for the medical audit advisory group. Of 997 audits described in detail, changes
      were reported as 'not needed' in 220 (22%), 'not made' in 142 (14%), 'made' in
      439 (44%), and 'made and remeasured' in 196 (20%). Thus, 635 (64%) audits were
      reported to have led to changes. Some 853 (81%) of the topics identified were on
      clinical care. Responders made 242 (42%) positive comments on the future of
      clinical audit in primary care, and 152 (26%) negative views were recorded.
      CONCLUSION: The level of audit activity in general practice is reasonably high,
      and most of the audits result in change. The number of audits per practice seems
      to be independent of the level of funding that the medical audit advisory group
      has received. Although there is room for improvement in the levels of effective
      audit activity in general practice, continued support by the professionally led
      audit groups could enable all practices to undertake effective audit that leads
      to improvement in patient care.

PMID- 9624770
TI  - General practitioner perceptions of treatment benefits and costs in patients with
      hyperlipidaemia.
AB  - This study explored general practitioner (GP) perceptions of use of treatments to
      manage hyperlipidaemia and their cost implications. GPs recognized different
      levels of coronary heart disease (CHD) risk, but were not always aware of which
      were major factors. Most were unfamiliar with published guidelines on managing
      hyperlipidaemia, and were likely to initiate drug therapies even in low-risk
      patients with mild hyperlipidaemia. Clearer advice is needed on whom to treat and
      on dietary intervention with high-fibre as well as low-fat diets.

PMID- 9624771
TI  - Teenagers and risk-taking: pregnancy and smoking.
AB  - Teenage pregnancy and teenage smoking are both areas of concern in the United
      Kingdom. This study found that girls who had had a teenage pregnancy were more
      likely to smoke than those who had not conceived as teenagers.

PMID- 9624772
TI  - How accurately do parents collect urine samples from their children? A pilot
      study in general practice.
AB  - Childhood urinary tract infections (UTIs) are of great importance, but few data
      exist on how accurately parents collect urine samples. By instituting three
      simple, practical changes we reduced the contamination rate from 27.5% to 13.2%.

PMID- 9624773
TI  - Streptococcal infection observed in the autumn of 1995.
AB  - Near patient testing demonstrated an unusual infection pattern with a high
      incidence of Lancefield group D beta-haemolytic streptococci in patients with
      pharyngitis and tonsillitis in a London general practice. This raises questions
      regarding the epidemiology of this streptococcus strain, which is not usually
      associated with upper respiratory infections.

PMID- 9624775
TI  - James Mackenzie Lecture 1997. The place of the humanities in the education of a
      doctor.

PMID- 9624776
TI  - Teenagers' views on seeking contraceptive advice.

PMID- 9624774
TI  - Implementing guidelines and innovations in general practice: which interventions
      are effective?
AB  - BACKGROUND: It is crucial that research findings are implemented in general
      practice if high-quality care is to be achieved. Multifaceted interventions are
      usually assumed to be more effective than single interventions, but this
      hypothesis has yet to be tested for general practice care. This review evaluates
      the effectiveness of interventions in influencing the implementation of
      guidelines and adoption of innovations in general practice. A systematic
      literature study was carried out using MEDLINE searches for the period from
      January 1980 until June 1994, and 21 medical journals were searched manually.
      Randomized controlled trials and controlled before and after studies (with pre-
      and post-intervention measurements in all groups) were selected for the analysis.
      Clinical area, interventions used, methodological characteristics and effects on
      clinical behaviour were noted independently by two researchers using a
      standardized scoring form. Of 143 studies found, 61 were selected for the
      analysis, covering 86 intervention groups that could be compared with a control
      group without the intervention. Information transfer alone was effective in two
      out of 18 groups, whereas combinations of information transfer and learning
      through social influence or management support were effective in four out of
      eight and three out of seven groups respectively. Information linked to
      performance was effective in 10 out of 15 groups, but the combination of
      information transfer and information linked to performance was effective in only
      three out of 20 groups. Some, but not all, multifaceted interventions are
      effective in inducing change in general practice. Social influence and management
      support can improve the effectiveness of information transfer, but information
      linked to performance does not necessarily do so. The variation in the
      effectiveness of interventions needs further analysis.

PMID- 9624777
TI  - Primary care services for problem drug users.

PMID- 9624778
TI  - Prostate specific antigen in urinary tract infection.

PMID- 9624780
TI  - De-reimbursement of vaccines.

PMID- 9624779
TI  - Hospice-at-home.

PMID- 9624781
TI  - HIV.

PMID- 9624782
TI  - Waiting for coronary bypass surgery: a lottery that fails to prevent avoidable
      death.

PMID- 9624783
TI  - A multicentre, double-blind, randomised study comparing the efficacy and safety
      of oral levofloxacin versus ciprofloxacin in the treatment of uncomplicated skin
      and skin structure infections.
AB  - A multicentre, randomised, double-blind trial in Latin America compared oral
      levofloxacin 500 mg once daily for 7 days with oral ciprofloxacin 500 mg twice
      daily for 10 days in 272 patients with uncomplicated skin and skin structure
      infections. Among 253 subjects evaluable for clinical efficacy (129 levofloxacin,
      124 ciprofloxacin), clinical success (cure and improvement) was observed in 96.1%
      of levofloxacin-treated patients and in 93.5% of ciprofloxacin-treated patients.
      Overall, bacteriological eradication rates by pathogen were 93.2% and 91.7%,
      respectively. Levofloxacin eradicated 94% (66/70) of Staphylococcus aureus and
      94% (17/18) of Streptococcus pyogenes isolates, compared with 93% (70/75) and 92%
      (12/13) for ciprofloxacin. Microbiological eradication rates by subject were
      approximately 93% and 90% for the levofloxacin and ciprofloxacin groups,
      respectively. Drug-related adverse events were reported by 8.9% of those
      receiving levofloxacin and 8.2% of those administered ciprofloxacin. Findings
      support the efficacy of oral levofloxacin for uncomplicated skin and skin
      structure infections due to S. aureus and S. pyogenes.

PMID- 9624784
TI  - Morning versus evening dosing with doxazosin in benign prostatic hyperplasia:
      pharmacokinetics, efficacy and safety.

PMID- 9624785
TI  - Cerebral ptosis revisited.
AB  - We studied nine patients with cerebral ptosis and gaze deviation following an
      acute stroke. The brains of all nine showed an extensive lesion in the fronto
      parieto-temporal regions. In five the stroke was left hemispheric. The assumption
      is that cerebral ptosis may have a bihemispheric representation and results from
      damage to the connections rather than to a specific area.

PMID- 9624786
TI  - Controlled trial of the subjective patient benefits of accompanied walking to the
      operating theatre.
AB  - A trial was carried out to determine if walking unpremedicated patients to the
      operating theatre would prove acceptable to the patients. One hundred surgical
      patients from a short-stay-ward were randomised into experimental (walked to
      theatre by ward nurse) and control (taken to theatre on a hospital trolley)
      groups. Seventy-eight patients responded to a questionnaire; a large majority
      indicated they would like to be given the choice of mode of conveyance and
      perceived this as an improvement in patient care. The results showed that a more
      favourable impression of walking to the theatre was given by patients who had
      actually experienced it, and of those given the opportunity to walk, almost all
      reported that it made them feel more relaxed. The findings are discussed in
      relation to patient choice, efficiency gains and a reduction in manual handling.

PMID- 9624787
TI  - Comparison of efficacy and ease of handling of salmeterol and terbutaline powder
      inhalers.
AB  - A multicentre, randomised, open, parallel-group study was performed to compare
      the efficacy, tolerability and ease of handling of salmeterol xinafoate 50
      micrograms twice daily via the Diskus inhaler with terbutaline sulphate 500
      micrograms four times daily via the Turbuhaler inhaler. Two hundred and sixty
      three patients (aged 18-79 years, baseline FEV1 50-90% predicted, mean PEFR 85%
      of response to salbutamol) were randomised to treatment with salmeterol (n = 136)
      or terbutaline (n = 127). A statistically significant difference in favour of
      salmeterol was seen between treatment groups for the primary efficacy variable,
      mean morning PEFR (difference in adjusted means 25.4 l/min, p < 0.001). Within
      the groups randomised to each device, ease of handling assessments favoured the
      Diskus inhaler over the Turbuhaler inhaler. More patients liked the Diskus
      inhaler than the Turbuhaler inhaler (98% vs 72%, p < 0.001). The Diskus inhaler
      received better scores than the Turbuhaler inhaler for all features assessed in
      the device questionnaire.

PMID- 9624788
TI  - A comparison of a community mental health centre-based psychiatric service with
      one based in an outpatient department at the same hospital.
AB  - Referrals and response to referrals of two psychiatric services with similar
      catchment areas of the same hospital, one with a Community Mental Health Care
      (CMHC) centre and the other based at an outpatient department, were compared over
      a five-month period. While the service with a CMHC had an increased number of
      referrals, which may reflect the aims of the CMHC of making mental health
      services more accessible and less stigmatised, most referrals were from general
      practitioners and therefore likely to be appropriate. In spite of its increased
      workload, the time from referral to assessment for the CMHC-based service was
      significantly shorter than for the outpatient-based service.

PMID- 9624790
TI  - Hormone replacement therapy and breast cancer.
AB  - Hormone replacement therapy (HRT) leads to a similar annual increase in risk of
      breast cancer as does each extra year of remaining premenopausal. Taken for more
      than 10 years HRT leads to a 35% increase in risk of developing breast cancer. It
      does not increase a woman's risk of dying of breast cancer, and may improve the
      prognosis. Some breast cancer patients can safely take HRT and some formulations
      might reduce the subsequent risk of relapse.

PMID- 9624789
TI  - Antiplatelet drugs in secondary prevention of stroke.
AB  - Stroke is a leading cause of long-term disability and death in developed
      countries. The primary medical strategy for secondary prevention of stroke is
      antiplatelet therapy. Although the clinical value of acetylsalicylic acid (ASA)
      is well recognised for preventing secondary stroke, several questions remain.
      What is the optimal dose of ASA to prevent stroke? Would combining ASA with
      another antiplatelet drug increase efficacy? Do new agents currently under
      development offer additional benefits? Many of the recent clinical trials address
      these questions. This review article summarises the results of these trials in
      the context of evolving strategies for stroke prevention, including the
      management of recurrent transient ischaemic attacks (TIAs), side-effects of ASA,
      and economic issues.

PMID- 9624791
TI  - Contraception: a review.
AB  - Recent years have seen a dual development in contraception: on the one hand,
      advances in technology have widened the choice for women; on the other, the right
      of women to informed and free choice has been reaffirmed. The need to provide
      contraceptive users with impartial and up-to-date advice was highlighted by the
      pill scare of 1995. The extreme safety of the pill when used by low risk women
      was confirmed in several reports. However, interest in long-acting systemic non
      oral methods continues to increase as providers seek methods with minimal
      compliance requirement and therefore higher efficacy which, in the case of the
      hormone releasing intrauterine system (IUS) and injectable progestogens, approach
      the efficacy of female sterilisation. Globally the intrauterine device (IUD) had
      topped the league of reversible contraceptives for many years but had had mixed
      fortunes in some developed countries, especially the US. A revival of the IUD is
      on the way, mainly because of the impressive performance of the IUS and the
      recent introduction of a frameless device, the GyneFix.

PMID- 9624792
TI  - Obstructive sleep apnoea syndrome: cardiopulmonary and diffuse manifestations.
AB  - Obstructive sleep apnoea syndrome mainly affects males over 40 and is thought to
      occur as a result of soft tissue laxity in the buccal and pharyngeal musculature.
      It is associated with changes in blood oxygen saturation and may lead to
      pulmonary hypertension and cardiac arrhythmias. Investigations should include
      routine haematological tests and, if possible, polysomnography. The main aim of
      therapy is to reverse as many risk factors as possible, i.e. alcohol consumption,
      obesity and smoking. Nasal continuous positive airway pressure is a useful tool
      in treatment but patient compliance may be poor, so surgery may be indicated. The
      surgical intervention of choice is uvulopalatopharyngoplasty, which is of most
      benefit to the patient with an upper airway laxity with an obstruction only at
      this level.

PMID- 9624793
TI  - Growth hormone therapy for adult growth hormone deficiency.
AB  - Growth hormone deficiency in adult life is associated with a number of adverse
      biological changes which include osteopenia, reduced exercise capacity, altered
      body composition, deleterious alterations in the lipid profile and insulin
      status, and reduced quality of life. Most of these changes can be reversed by
      growth hormone replacement therapy, but in an era of health rationing, such
      therapy is unlikely to be offered to every growth hormone deficient adult.
      Therefore we have proposed a strategy aimed at delineating which adults with
      growth hormone deficiency might benefit most from growth hormone therapy.

PMID- 9624794
TI  - Biochemical investigation of diabetes mellitus.
AB  - Simple biochemical investigations serve to identify diabetes, can assist in its
      management, and facilitate the early recognition of complications. This review
      outlines some of the applications of various relevant test procedures.

PMID- 9624795
TI  - Treatment of pain with sustained-release tramadol 100, 150, 200 mg: results of a
      post-marketing surveillance study.
AB  - In a post-marketing-surveillance study the use of a sustained-release tramadol
      preparation (Tramal long 100, 150, 200 mg) was investigated in 3153 patients. The
      intention was to comply with the legal obligation to carry out product
      surveillance and to collect data on prescribing behaviour. We focused our
      attention on drug safety and efficacy. Tramal long was used mainly for severe and
      very severe pain. The most frequently reported causes of pain were diseases of
      the locomotor system (49.9%), tumours (24.3%), traumas and fractures (10.1%), and
      neurogenic (9.3%). The mean daily dose was 235.7 mg, usually divided into two
      doses. The analgesic effect was described as very good or good by 82.5% of the
      patients. Adverse events occurred in 6.5% of the patients, mostly in the form of
      typical opioid side-effects such as nausea (3.4%), dizziness (1.5%) and vomiting
      (1.1%). Severe or unknown side-effects were not reported.

PMID- 9624796
TI  - An unusual presentation of sacral agenesis in a newborn baby.
AB  - A potentially difficult situation can arise when a sick newborn baby presents
      with a common clinical sign that subsequently turns out to be a manifestation of
      a rare condition. The baby's birth sometimes results in the diagnosis of a new
      condition in other members of the family. Necrotising enterocolitis is the
      commonest surgical condition among babies in the neonatal intensive care unit
      (NICU). We report a case where abdominal distension in an acutely ill baby at
      high risk of necrotising enterocolitis masqueraded as an unusual presentation of
      familial sacral agenesis.

PMID- 9624797
TI  - Saved by a hernia: an unusual presentation of ovarian cancer.
AB  - A lump in the groin of a 75-year-old woman co-existed with a single ovarian cyst.
      It was eventually diagnosed as a solitary necrotic omental metastasis from a
      cystadenocarcinoma of the ovary which had herniated through the femoral canal.

PMID- 9624798
TI  - Sudden onset deafness: two cases associated with pregnancy.
AB  - Sudden onset sensorineural deafness is an otological emergency; subsequent
      recovery of hearing has been shown to correlate with early treatment. There have
      been few documented reports of this occurring in pregnancy, although the
      increased thrombogenic risk of the pregnant state is a proposed aetiological
      factor. The wide variation in outcome is demonstrated by these two cases, which
      are presented to raise awareness of this condition.

PMID- 9624799
TI  - Fibrous contracture of the elbow following cannulation of the antecubital fossa
      vein.
AB  - A case of flexion contracture of the elbow resulting from thrombophlebitis is
      described. Thrombophlebitis is a recognised complication following cannulation of
      the antecubital fossa vein. In severe cases a tender fibrous band is palpable.
      There are no previous reports of a contracture deformity occurring from such a
      fibrous band. This case therefore presents an unusual clinical manifestation of
      thrombophlebitis not previously described.

PMID- 9624800
TI  - Community-acquired Clostridium difficile-associated diarrhoea in a patient with
      colonic carcinoma.
AB  - In the vast majority of cases, Clostridium difficile-associated diarrhoea and
      pseudomembranous colitis develop following the use of antibiotics. We report a
      case in which C. difficile-associated diarrhoea was diagnosed in the absence of
      previously reported predisposing factors. It transpired that the patient had a
      colonic carcinoma. We suggest that a diagnosis of C. difficile-associated
      diarrhoea in the absence of a history of antibiotics or other established causes
      should prompt a colonoscopy to search for alternative explanations for the
      alteration in bowel flora which such an infection indicates.

PMID- 9624802
TI  - Soldiers, surgeons and the campaigns to combat sexually transmitted diseases in
      colonial India, 1805-1860.

PMID- 9624801
TI  - Emla cream as a local anaesthetic in MMR vaccination.

PMID- 9624803
TI  - The use of chloroform by British Army Surgeons during the Crimean War.

PMID- 9624804
TI  - Gender differences in the licensing and practice of female and male surgeons in
      early modern England.

PMID- 9624805
TI  - "No small uncertainty": eye treatments in eighteenth-century England and France.

PMID- 9624806
TI  - The Obstetric Society of 1825.

PMID- 9624807
TI  - 1997 JB Firth Memorial Lecture. "No more twist".

PMID- 9624808
TI  - Discharge residue from mercury fulminate-primed ammunition.
AB  - The scarcity of mercury in discharge residue particles from mercury-containing
      ammunition was investigated. It was found that 86% of the mercury was vaporized
      after discharge, mainly via the muzzle, 88% of which was not detectable by SEM.
      Of the 0.16% exiting via the breech, only approximately 40% was detectable by
      SEM. Only a small proportion of this was deposited on the firer. The recovered
      mercury did not make a significant contribution to the elemental composition of
      the discharge residue particles. The rate of loss of mercury from the spent
      cartridge case was also examined but was found to be of no practical value in
      estimating time of discharge.

PMID- 9624809
TI  - Assessing transfer probabilities in a Bayesian interpretation of forensic glass
      evidence.
AB  - When someone breaks glass a number of tiny fragments may be transferred to that
      person. If the glass is broken in the commission of a crime then these fragments
      may be used as evidence. A Bayesian interpretation of this evidence relies on the
      forensic scientist's ability to assess the probability of transfer. This paper
      examines the problem of assessing this probability and suggests some solutions.

PMID- 9624810
TI  - Setting bounds for the likelihood ratio when multiple hypotheses are postulated.
AB  - The interpretation of mixtures of DNA in the forensic context presents particular
      challenges. The only logical means available for dealing with them is through
      Bayesian inference, which leads to the formulation, in most cases, of a
      likelihood ratio which weighs the evidence in favour of two competing hypotheses.
      However, situations can arise in which additional hypotheses are proposed and the
      authors discuss one such situation--that where the number of contributors to the
      mixture is in dispute. A way of dealing with the problem is presented.

PMID- 9624811
TI  - Characteristic dye absorption peaks found in the FTIR spectra of coloured acrylic
      fibres.
AB  - The improved quality of spectra recorded using FTIR-microspectroscopy has meant
      that a lot more information is now obtainable from the spectra of dyed acrylic
      fibres. In addition to the main absorptions produced by the polymer material,
      additional absorptions resulting from the fibre dye are often present. An attempt
      has been made to explain some of the strongest and most frequently seen dye bands
      with the aid of spectra obtained from fibres treated with known dyes. Provided
      the dye concentration in the fibre is sufficient, it is possible to make some
      general observations on the type of dyes which have been used. Further
      investigation in conjunction with HPLC or FTIR-Raman spectroscopy would be
      useful.

PMID- 9624812
TI  - A target fibre study on seats in public houses.
AB  - A target fibre survey was conducted to assess the random occurrence of a blue
      wool fibre on seats in public houses throughout the United Kingdom. Fibre tape
      lifts were taken from 80 seats. Four seats yielded matching fibres and five of
      these were found on one seat. A total of 292 fibres were identified; nine fibres
      proved indistinguishable from the target after comparison microscopy,
      microspectro-photometry and attempts at thin layer chromatography, and two of
      these fibres were still apparently indistinguishable after TLC analysis although
      only one dye component was visible.

PMID- 9624813
TI  - Deviation of the path of a sliding object due to road camber.
AB  - After a road accident, slide marks are sometimes seen to exhibit a slight
      curvature, which is often due to road camber. The lateral deviation from that
      cause is shown to be the length of the slide multiplied by the lateral gradient
      and divided by twice the friction coefficient.

PMID- 9624814
TI  - The role of the forensic scientist in an inquisitorial system of justice.

PMID- 9624815
TI  - An overview of the scientific examinations performed after an explosion on the
      Shankill Road.
AB  - In October 1993 an explosion occurred in a busy fish shop on the Shankill Road in
      Belfast resulting in the deaths of ten people and multiple casualties.
      Examinations were carried out by forensic scientists at the scene and in the
      laboratory to determine the cause of the explosion and to establish evidence of
      contact between the suspects and the incident.

PMID- 9624816
TI  - Cartridge discharge residue contamination--the search for the source.
AB  - The detection of cartridge discharge residue (CDR) particles on some control
      samples in a firearms case started an extensive search to discover their origin.
      Investigation of potential sources of the contamination showed that it was
      airborne but random in nature, and it is recommended that frequent examination of
      air control samples should be made in contamination-sensitive areas.

PMID- 9624817
TI  - The role of the forensic scientist at pseudo-military incidents.
AB  - Most forensic scientists called to a scene are briefed by a police officer and
      requested to carry out a specific function. The investigation of terrorist
      incidents in Northern Ireland provided a major challenge for scientists,
      involving large numbers of participants and several separate scenes. In two such
      cases, the areas initially sealed off were confined to the obvious focus of
      interest, the bodies and the damaged building, but the scenes expanded to other
      areas, including firing points and escape routes, house take-overs, hostage
      situations, and abandoned vehicles thought to have been used in the incidents.
      Because of security factors, all these scenes had to be examined quickly to
      preserve any evidence yet carefully to avoid contamination and to ensure the
      safety of all the personnel involved.

PMID- 9624818
TI  - Discrimination of glass sources using elemental composition and refractive index:
      development of predictive models.
AB  - Refractive index and metal ion concentrations (Al, Ba, Ca, Fe, Mg, Mn, Sr, Ti and
      Zr) were determined for four product-use categories: headlamp glass; container
      glass, non-vehicle window float glass, and vehicle float glass. Linear
      discriminant modelling using these data allowed differentiation of the four glass
      types but further discrimination was not possible within a product-use category.
      For this specific set of glasses, the concentrations of a number of metal ions
      were found to be correlated in some cases. This precluded the use of traditional
      probability calculations in using elemental composition data for interpretation
      of glass evidence. Alternative approaches to glass data interpretation are
      suggested.

PMID- 9624819
TI  - Sampling in forensic comparison problems.
AB  - When someone breaks glass a number of tiny fragments may be transferred to that
      person. If the glass is broken in the commission of a crime then these fragments
      may be used as evidence. If a large number of fragments are recovered from the
      suspect, then it may be more efficient for the forensic scientist to examine a
      subset of these fragments. Such sampling incurs information loss. This paper will
      derive an expression that allows a partial quantification of this loss. The loss
      of such information due to the examination of a subset of recovered material
      arises with many forms of evidence.

PMID- 9624820
TI  - The effects of commonly used adulterants on the detection of spiked LSD by an
      enzyme immunoassay.
AB  - The effects of 15 chemicals and household agents on an enzyme immunoassay (EIA)
      for LSD were investigated. The presence of many of these was detected by pH and
      specific gravity measurements and by sample inspection. A number of agents caused
      false positives in the assay at 10% adulteration, but only two produced false
      positive results at 1%. Adulterated samples spiked with LSD produced no false
      negatives, demonstrating that none of the adulterants tested were able to conceal
      the presence of LSD by interfering with the EIA. The assay is shown to be a
      robust method for the screening of urine for LSD when used in conjunction with
      sample inspection and a sound confirmatory method.

PMID- 9624821
TI  - Ballpoint ink flakes as indicators of added entries.
AB  - Examiners were asked to determine if an entry made in a diary had been completed
      at one time, or if the last sentence of the entry had been added later. Standard
      non-destructive ink differentiation techniques did not show any differences in
      the ballpoint pen ink used. Dried flakes of ballpoint pen ink were present in the
      initial stroke of the questioned sentence, but did not appear elsewhere in the
      entry. Experiments were undertaken to ascertain if these dried flakes could be
      attributed to a time delay or some other cause. Experimentation showed that ink
      flakes occurred only after periods of non-use of the ballpoint pens in the
      sample. Caution is urged in applying this finding to actual case work.

PMID- 9624822
TI  - Diagnosis and management of complicated gout.
AB  - Although a diagnosis of gout can be confirmed by the presence of monosodium urate
      crystals in synovial fluid, arriving at the suspected diagnosis and managing the
      disease can be a challenge for primary care physicians and specialists alike.
      Symptoms of gout can mimic other forms of inflammatory arthritis such as
      rheumatoid arthritis, pseudogout, or septic arthritis. Treatment can be
      complicated by the patient's need for drugs that contribute to hyperuricemia.
      Once other diagnoses are ruled out and urate crystals are detected under
      polarized light microscopy, treatment to end the acute attack and follow-up
      treatment designed to lower serum urate levels can be undertaken.

PMID- 9624823
TI  - Joint replacement surgery: preoperative management.

PMID- 9624824
TI  - [Pathology on the Internet].
AB  - Authors' experience gained during a one year usage of the Internet is presented.
      By now we have found many useful information resources related to the field of
      pathology. The MEDLINE database is available free of charge at several web sites
      as well as teaching diagnostic seminars, electronic color atlases, medical
      publishers homepages, etc. There is also a possibility to enter various topic
      related groups in the framework of Internet discussion groups. The limiting
      factors for reaching medical information from the Internet is hardware and
      software equipment, the cost of Internet connection, and the data transmission
      capacity of phone lines.

PMID- 9624825
TI  - [Mantle cell lymphoma (MCL)--histopathology and clinical features].
AB  - Mantle cell lymphoma (MCL) has been established as a clinicopathologic entity in
      1991. A histopathologic and immunohistochemical study of 16 cases of MCL was
      performed in order to demonstrate differential diagnostic aspects. MCLs were
      composed of small and medium-sized B cells assuming the appearance of
      centrocytes. The growth pattern was diffuse in 9 cases and that of follicle
      mantle zone type within at least partially present nodular parts in 16 cases. The
      immunohistochemical staining for CD23 antigen was negative in tumour cells
      whereas the strong immunoreactivity of follicular dendritic cells (FDC) decorated
      residual FDC network. Seven cases of MCL were examined for the presence of
      translocation t(11;14)(q13;q32) using polymerase chain reaction. Despite
      histomorphological features compatible with a diagnosis of low-grade lymphoma,
      MCL has a worse prognosis and more aggressive behaviour than other types of small
      cell lymphomas, such as small lymphocytic lymphoma and follicle centre lymphoma.

PMID- 9624826
TI  - [Paratesticular spindle cell embryonal rhabdomyosarcoma in a 50-year-old man
      (case report)].
AB  - Spindle cell subtype of embryonal rhabdomyosarcoma in paratesticular region was
      diagnosed in a 50 year-old man. This relatively rare entity was constituted in
      1992 and observed but in children up to now.

PMID- 9624827
TI  - [Solitary fibrous tumor (fibrous mesothelioma). Report of 2 cases in an
      extraserous location].
AB  - Two cases of extraserosal solitary fibrous tumour occurring in the orbit and in
      the meninx are described. The orbital tumour contained, besides the well known
      features of this entity, nuclear palisading resembling rudimentary Verocay bodies
      which are considered typical of nerve sheath tumours. In the meningeal case there
      was close resemblance to fibrous meningioma and meningeal haemangiopericytoma.
      However, the tumour cells in both cases were negative for immunohistochemical
      markers of neural and meningeal differentiation (S-100 protein, neuron-specific
      enolase, glial fibrilary acidic protein, myelinic basic protein, Leu-7,
      epithelial membrane antigen) and reacted diffusely with CD34, CD99 and vimentin.
      The finding of nuclear palisading in one case reflected the great morphologic
      variability of extraserosal solitary fibrous tumour and might be misinterpreted
      as a feature of neurogenic tumour.

PMID- 9624828
TI  - [A bizarre inflammatory polyposis of the colon in chronic ulcerative
      proctocolitis].
AB  - A case report of a young patient (born in 1980) with a 2-year history of chronic
      ulcerative proctocolitis was described. Checking colonoscopy 6 months from the
      beginning of disease showed multiple and even confluent polypoid lesions in
      transverse gut starting from hepatic flexure in addition to diffuse inflammatory
      rectosigmoideal changes. Biopsy found only colic mucosa without any tumorous
      structures. Five months later the patient's state got worse accompanied instantly
      by vomiting, weight loss and malabsorption symptoms. A duodenocolic fistula was
      supposed according to gastroduodenoscopy and biopsy. Because of progressive
      suffering of the patient colectomy with ileoduodenoanastomosis and
      ileosigmoidoanastomosis was performed. Polypous lesions were observed from the
      blind gut up to descendent colon and a transversoduodenal fistula was proved. The
      removed part of gut was completely changed into a dense network of elongated
      polypous lesions. In microscopy, bigger polyps showed an inner stromal part often
      with bands of smooth muscle cells covered by nearly normal gut mucosa. Smaller
      polyps were formed by hypertrophic gut mucosa only. At the base of polyps, a
      stagnation of gut contents was found as well as ulcerous defects of various
      depth. Macroscopy and microscopy of polypoid lesions formed by non-neoplastic gut
      mucosa were those of so called bizzare ("giant") inflammatory polyposis of the
      gut. Up to now the patient's clinical picture and local finding in the stump of
      resected gut have been typical for chronic ulcerous colitis and polypous lesions
      were not revealed by checking investigations.

PMID- 9624829
TI  - [Morphologic findings in liver tissue in mice after long-term administration of
      the herbicide fomesafan].
AB  - Administration of herbicide fomesafen and of fomesafen combined with one dose of
      iron to 44 mice during 3 to 14 months caused hyperplastic and preneoplastic
      changes in the liver tissue which had been described in experimental
      carcinogenesis* small groups of altered hepatocytes storing glycogen or lipids
      and foci of small basophilic liver cells occurred as early as after 3 months.
      Altered hepatocytes were found more frequently in mice getting fomesafen and
      iron. Later nodular hyperplasia of liver cells developed with nodes 3-20 mm in
      diameter which mostly consisted of altered hepatocytes with plenty of glycogen.
      After 12 and 14 month-lasting administration of fomesafen and fomesafen with
      iron, the hepatocellular carcinoma was proved in 5 mice. In 4 mice, the
      preneoplastic changes in liver tissue were accompanied by micronodular
      hyperplasia of liver cells which did not participate on the development of big
      nodes and hepatocellular carcinoma.

PMID- 9624830
TI  - [Over a half-century at the Medical School of Charles University: 1. Student
      years].
AB  - Nearly all student years in Prague Medical School represented a "big class"
      schooling. Professors and their lectures were in the centre of programme and
      practical training was very limited. Interruption of studies during the war
      brought many difficulties but was in a way positive for those who had opportunity
      to further practical education. We found out that even a very good preparation by
      the medical school did not do and had to be complemented by the school of
      practice. Its standardization could be hardly achieved without any connection
      with a university department.

PMID- 9624831
TI  - [Schedule of aggregated procedures. Recommendations of the Society of Private
      Pathologists].

PMID- 9624832
TI  - [The histopathologic picture of experimental poisoning with ethylmethacrylates].
AB  - Toxic effect of hydroxyethylmethacrylate, acetoxyethylmethacrylate and
      diethylenglycomethacrylate were studied in rats surviving as long as 1 to 20 days
      after intramuscular administration. Conspicuous lesion were found only in calf
      muscles at the site of application. Muscle fibre necroses with inflammatory
      reaction occurred repeatedly in animals surviving 1-2 days. Newly formed
      connective tissue replacing impaired muscle fibres was found in rats surviving 5
      days. Intoxication related other lesion in rat organs were not identified.

PMID- 9624833
TI  - [Isolation and identification of benzodiazepines using thin-layer
      chromatography].

PMID- 9624834
TI  - Minimal government.

PMID- 9624835
TI  - Are clinical guidelines necessary?

PMID- 9624836
TI  - Atmospheric ozone layer--its depletion can affect our health.

PMID- 9624837
TI  - Obstetric performance, perinatal outcome and risk of infection to the newborn in
      spontaneous and artificial rupture of membranes during labour.
AB  - OBJECTIVE: To compare the obstetric performance, perinatal outcome and risk of
      neonatal infection in labour following spontaneous (SROM) and artificial (AROM)
      rupture of membranes. DESIGN: Prospective, non-randomised, comparative study
      during a one-month period in 1995. The study was approved by the ethics committee
      of the Faculty of Medicine, University of Colombo. SETTING: University Obstetrics
      Unit at De Soysa Hospital for Women, Colombo. PATIENTS: 324 women who were in
      early established labour after 37 weeks of gestation. 151 of these had SROM and
      173 AROM. The AROM and SROM groups among primigravidae and multigravidae were
      considered separately. RESULTS: Oxytocin use in multigravidae was significantly
      higher in the AROM group than in the SROM group (p < 0.001). The emergency
      caesarean section (LSCS) rate in primigravidae was significantly higher in the
      AROM group than the SROM group (p < 0.001). A significantly larger number of
      primigravid AROM women had abnormal fetal heart rate changes on auscultation (p <
      0.05) and cardiotopographic (CTG) patterns (p < 0.001) when compared with
      primigravid SROM women. Choreoamnionitis and funisitis were commoner in the AROM
      group although the difference was not statistically significant. CONCLUSIONS:
      AROM appears to be associated with a higher chance of fetal distress particularly
      in primigravidae. Both AROM and SROM are associated with a potential risk of
      infection at intrauterine sites.

PMID- 9624838
TI  - Plasma pharmacokinetics of a generic amoxycillin and the innovator brand: a
      comparison.
AB  - OBJECTIVE: To compare the bioavailability and plasma pharmacokinetics of a
      generic brand of amoxycillin (State Pharmaceutical Manufacturing Coporation)
      selected from the lower price range, with that of the innovation brand (Amoxil,
      Beecham). DESIGN: Sixteen healthy adult volunteers were allotted to two groups
      and each group was given a test dose of amoxycillin from each brand. Blood
      samples were collected at 0, 2, 3 and 4 hours thereafter plasma levels were
      assayed using high performance liquid chromatography. RESULTS: Analysis of
      results show that the generic product had similar bioavailability and
      pharmacokinetics when compared with the innovator product. CONCLUSION: The
      quality assured generic amoxycillin tested had similar bioavailability as a more
      costly branded version.

PMID- 9624839
TI  - The prevalence of peripheral neuropathy in newly diagnosed patients with non
      insulin-dependent diabetes mellitus.
AB  - INTRODUCTION: Neuropathy is considered to be a longterm complication of diabetes.
      AIMS: To determine the prevalence of peripheral neuropathy in 112 Sri Lankan
      patients with recently diagnosed non-insulin-dependent diabetes and a control
      population of 100 people. METHODS: A diagnosis of peripheral neuropathy was made
      using a clinical symptom score, clinical examination, quantitative sensory
      testing and electrophysiological studies. RESULTS: 9.8% of diabetic patients at
      diagnosis had peripheral neuropathy, 2.6% had foot ulcers, 7.1% had signs of
      neuropathy, abnormal vibration perception threshold and nerve conduction
      abnormalities and 15.1% had abnormal nerve conduction velocity without signs or
      symptoms of neuropathy. The peroneal nerve conduction velocity was higher in
      diabetic patients when compared to controls. There was an inverse correlation
      between nerve conduction velocity and fasting blood glucose in diabetic patients
      (p < 0/05). This association was stronger for peroneal nerve conduction velocity
      (r = -0.73) than for median nerve motor conduction velocity (r = -0.42).
      CONCLUSIONS: Symptomatic peripheral neuropathy is common among Sri Lankans with
      newly diagnosed non-insulin-dependent diabetes. This may be due to a later
      presentation of diabetes or a genetic predisposition.

PMID- 9624840
TI  - Organophosphorus insecticide poisoning.
AB  - Organophosphorus insecticides (OPI) are the commonest cause of poisoning in Sri
      Lanka. Being inhibitors of esterases, OPI cause an acute cholinergic crisis as
      the initial phase of neurotoxicity. The intermediate syndrome (IMS) which
      develops 24 to 96 hours after poisoning, and the delayed polyneuropathy (OPIDP)
      which manifests several weeks later, suggest a triphasic effect of OP
      intoxication. OPI may also cause extrapyramidal manifestations. Chronic
      neurobehavioural effects of longterm exposure to OPI are also a cause for
      concern. This paper reviews OPI poisoning in man emphasising the clinical,
      biochemical, and electrophysiological studies done at Peradeniya over the past
      two decades.

PMID- 9624841
TI  - Red (wo)man syndrome.

PMID- 9624842
TI  - Essential thrombocythemia: an uncommon cause of digital gangrene.
AB  - We describe a case of essential thrombocythemia (ET), presenting as digital
      gangrene. ET is a rare myeloproliferative disorder characterised by a
      persistently elevated platelet count which commonly presents with haemorrhagic
      manifestations. Thrombosis occurs less frequently and digital gangrene is an
      uncommon presentation.

PMID- 9624843
TI  - Suicide by suffocation with a plastic bag.
AB  - Death by suffocation using a plastic bag has not been recorded in Sri Lanka. We
      report such a case here. Findings at the scene, the history, and autopsy and
      laboratory investigations assisted in arriving at the conclusion of suicide.

PMID- 9624844
TI  - Two definitive cases of concealed homicide and one inconclusive case.

PMID- 9624845
TI  - Leiomyosarcoma of the inferior vena cava.
AB  - A 63-year old with an 8-month history of backache had a leiomyosarcoma of the
      inferior vena cava. Although inoperable, she benefitted from cobalt therapy. A
      review of the literature suggests an evolving clinical picture which will
      facilitate earlier diagnosis, and perhaps allow resection.

PMID- 9624846
TI  - Health-care and housing for prisoners.

PMID- 9624847
TI  - EPI vaccine storage and power cuts.

PMID- 9624848
TI  - Mass murderers.

PMID- 9624849
TI  - Bibliographic resources.

PMID- 9624850
TI  - We are the first...

PMID- 9624851
TI  - Increasing folic acid consumption.

PMID- 9624852
TI  - Knowledge about diabetes among final year medical students, non-specialist
      hospital doctors and general practitioners.

PMID- 9624853
TI  - An audit of the (ab)use of thyroid function tests.

PMID- 9624854
TI  - A hybrid of haemangiopericytoma and deep seated fibrous histiocytoma--a rare
      tumour of soft tissues.

PMID- 9624855
TI  - A Sri Lankan family with Alport's syndrome.

PMID- 9624856
TI  - Aerodynamic assessment of velopharyngeal function during normal speech containing
      different places of articulation.
AB  - The aim of this study was to describe the aerodynamics related to velopharyngeal
      function during speech in bilabial, dental, and velar articulatory positions in
      Swedish speakers. Repeated syllables including voiceless stop consonants and
      sentences including combinations of voiceless stops and nasal consonants were
      uttered by 11 normal adults. Oropharyngeal pressure was assessed with a miniature
      pressure transducer positioned transnasally, in combination with measurement of
      nasal pressure and nasal airflow. The corresponding velopharyngeal opening area
      was estimated. The results suggest that the velopharyngeal function during stop
      consonants is similar in different articulatory positions. Differences in
      oropharyngeal pressure and nasal airflow between bilabial versus dental and velar
      positions were found, presumably due to differences in volume and compliance of
      the vocal tract.

PMID- 9624857
TI  - Perceptions of tonal changes in normal laryngeal, esophageal, and artificial
      laryngeal male Cantonese speakers.
AB  - Listeners were asked to identify six tonal variations in the production of the
      syllables /ji/ and /si/ produced by 10 normal laryngeal (NL), 10 standard
      esophageal (SE), and 10 Servox-type electrolarynx (EL) Cantonese speakers. The
      purpose of the present study was to determine if alaryngeal Cantonese speakers
      could differentiate meanings associated with different tone levels. Results
      indicated that listeners' identification of the six tones for each syllable
      produced by the SE speakers was similar in pattern to those produced by the NL
      speakers of Cantonese. For both NL and SE speech, the high-level, low-falling,
      and high-rising tones were perceived more accurately than the mid-level, low
      level, and low-rising tones. Identification of the six tones for each syllable as
      produced by the EL speakers was significantly poorer due to the limitations of
      the electrolarynx.

PMID- 9624858
TI  - Diagnostic assessment and treatment goals in logopedics: impairments,
      disabilities and handicaps.
AB  - This study was aimed to investigate to what extent impairments, disabilities and
      handicaps are used as diagnostic assessments and treatment goals in logopedics.
      Traditionally, logopedists are mainly concerned with impairments. These days,
      increasing attention is demanded for disabilities and handicaps as well. A survey
      study was carried out on 1,567 patients in logopedic practices in the Netherlands
      to provide an empirical quantitative description of diagnostic assessments and
      treatment goals, formulated in terms of impairments, disabilities and handicaps.
      Results show that logopedists indeed often indicate impairments as diagnostic
      assessments and as treatment goals, particularly language development impairments
      and phonetic/phonological articulation impairments. Interestingly, also large
      numbers of diagnostic assessments and treatment goals were indicated at the level
      of disabilities and handicaps; the most important being disability in expressing
      communication and occupational handicap. These results demonstrate that
      disabilities and handicaps may serve an important function in logopedics, in that
      they may guide assessment as well as therapy. It is concluded that disabilities
      and handicaps should be considered in the future development of the profession of
      logopedics.

PMID- 9624859
TI  - Medical and educational fields in logopedics in The Netherlands: a comparison in
      historical and European perspective.
AB  - This study describes differences between medical and educational fields in
      logopedics practice in The Netherlands. This dichotomy of fields is also found in
      other Western European countries and may result from the historical development
      of the profession. The four settings where logopedists work the most
      (institutional care, private practice, community care and special schools) were
      studied. One hundred and seventy-two logopedists in 103 practices or departments
      collected data on 1,761 patients. For each patient a standard registration form
      was filled in, containing information on (i) patient characteristics, (ii)
      logopedic diagnostic assessment, and (iii) aspects of treatment. The historical
      dichotomy into medical and educational fields is still demonstrable in present
      day logopedics in The Netherlands. However, the settings within each field also
      show some differences. Private practice shows a mixture of medical and
      educational characteristics.

PMID- 9624860
TI  - Occurrence of dental consonant misarticulations in different cleft types.
AB  - To study the occurrence and type of misarticulations in dental consonants /r/,
      /s/ and /l/ 280 (115 girls, 165 boys) 6-year-old cleft children were examined by
      1 of the 2 experienced speech pathologists of the cleft team. The patients
      included 82 children with isolated cleft palate (CP), 82 with cleft lip with (34)
      or without (48) cleft alveolus [CL(A)], 85 with unilateral cleft lip and palate
      (UCLP) and 31 with bilateral cleft lip and palate (BCLP). CP children were first
      divided into subgroups; there were 17 children with soft palate cleft, 49 with
      partial and 16 with complete hard palate cleft. All patients were native Finnish
      speakers, and had normal hearing, no known syndrome or associated anomalies
      possibly affecting speech or psychomotor retardation. The results showed that the
      occurrence and severity as well as the number of errors of all studied sounds
      separately or grouped increased with the severity of the cleft being constantly
      greatest in the BCLP group and lowest in the CL(A) group. Altogether 44% of the
      patients misarticulated at least one studied sound; 41% distorted and 5%
      substituted, and 2% both distorted and substituted. The /r/ sound was
      misarticulated by 36%, the /s/ sound by 23%, and the /l/ sound by 18% of the
      patients. Boys tend to have more problems in producing the studied sounds
      correctly.

PMID- 9624862
TI  - Hepatitis E virus infection: where are we?

PMID- 9624861
TI  - Foetal solutions to a fatal epidemic: the relevance in India.

PMID- 9624863
TI  - Myocardial dysfunction in children with dengue haemorrhagic fever.
AB  - BACKGROUND: Dengue fever/dengue haemorrhagic fever/dengue shock syndrome is a
      serious health problem in tropical countries. Intravascular fluid depletion due
      to capillary leak is presumed to be the cause of hypotension in dengue
      haemorrhagic fever. The treatment guidelines of the World Health Organization lay
      stress primarily on monitoring and fluid replacement therapy. During the 1996
      epidemic in New Delhi, we observed problems in fluid management of such children
      and prospectively looked for myocardial dysfunction as an additional factor for
      hypotension. METHODS: Fifty-four children (< 12 years old) admitted to the All
      India Institute of Medical Sciences, New Delhi after 15 October 1996 with various
      grades of the disease, who were fit to be shifted to the echocardiography
      laboratory, were examined clinically and subjected to a detailed M-mode, 2
      dimensional and colour doppler echocardiography. Ejection fractions
      (Teichholz/Modified Simpson's) and shortening fractions were calculated. RESULTS:
      Ejection fraction by modified Simpson's rule was reduced (< 50%) in 9/54 (16.7%)
      children; 2 of these had significant reductions (< 35%). These 9 children
      belonged to all stages of clinical severity. Three of these 9 children who had a
      repeat echocardiogram within 2 months of the illness had improved ejection
      fractions. CONCLUSION: The role of myocardial dysfunction remains to be defined
      as there was no correlation with clinical severity. Myocardial functions need to
      be assessed in patients with this disease, especially those who have persistent
      hypotension in spite of adequate hydration.

PMID- 9624864
TI  - Neuropsychological impairment and altered thyroid hormone levels in epilepsy.
AB  - BACKGROUND: Neuropsychological impairment is a common problem in epilepsy which
      interferes with the quality of life of patients. Similarly, thyroid hormone
      levels have been observed to be abnormal in patients with epilepsy on various
      treatments. This study aimed to ascertain any possible correlation between
      neuropsychological performance and thyroid hormone levels among epilepsy
      patients. METHODS: Thyroid hormone levels, indices of neuropsychological
      performance and social adaptation of 43 epilepsy patients were compared with
      those of age- and sex-matched healthy control subjects. RESULTS: Epilepsy
      patients exhibited significantly (p < 0.001) lower scores on attention, memory,
      constructional praxis, finger tapping time, and verbal intelligence quotient
      (i.q.) when compared with controls. Their T3, T4 and Free T3 levels were
      significantly lower; and TSH and Free T4 levels were significantly higher than
      that of controls. There was no statistically significant correlation between the
      indices of neuropsychological performance and thyroid hormone levels. CONCLUSION:
      We did not observe any correlation between neuropsychological impairment and
      thyroid hormone levels among patients with epilepsy.

PMID- 9624865
TI  - Nutritional deficiency disorders and high mortality among children of the Great
      Andamanese tribe.
AB  - BACKGROUND: The population of the Great Andamanese tribe of the Andaman Islands
      has been declining at a rapid pace. The case fatality rate during a recent
      outbreak of dysentery was 30.8%, all the deaths being among under-fives. As
      malnutrition is known to potentiate susceptibility to death due to infectious
      diseases, we undertook a study to determine the prevalence of malnutrition among
      the Great Andamanese tribe and its role in contributing to the high mortality
      among them due to infectious diseases. METHODS: The study included a diet survey,
      nutritional anthropometry, clinical examination, haemoglobin estimation and stool
      examination for intestinal parasitic infestations. Information was also collected
      about every pregnancy in all ever-married women in the community and deaths of
      their children. All 36 members of the tribe were covered. RESULTS: The Andamanese
      had a poor intake of iron, vitamin A and riboflavin but a good intake of energy,
      protein and fats. More than 85% of the children below 6 years were under
      nourished and more than 77% of children and adolescents below 19 years were
      stunted, wasted or both. Anaemia, vitamin A deficiency and goitre were also
      common among them. Almost the entire population suffered from intestinal
      parasitic infestations. They also have a comparatively high fertility rate and a
      high infant mortality rate. CONCLUSION: The population attributable risk for
      death due to malnutrition is probably one of the foremost reasons for the
      observed high infant mortality rate among the Great Andamanese tribe and could be
      one of the reasons for the continuous decline in their population.

PMID- 9624866
TI  - Treatment-resistant depression: clinical significance, concept and management.
AB  - Depression is a common disorder which causes intense personal suffering and socio
      occupational dysfunction. It also imposes a heavy economic burden on society. It
      has been shown that between 29% and 46% of depressed patients fail to respond
      adequately to antidepressant medication. Treatment-resistant depression may
      contribute to the morbidity and mortality associated with affective illness. When
      treatment resistance is suspected, the patient's history should be reevaluated
      particularly regarding diagnostic subtypes and comorbidity. An assessment of
      treatment adequacy in terms of dose, duration and compliance should also be made.
      Treatment strategies for treatment-resistant depression should be systematic and
      empirically grounded because of the risk of increased resistance and loss of time
      in case of a random trial-and-error approach, and the inherent risks in certain
      novel strategies. A stepped care approach to treatment-resistant depression
      involves optimization of the current drug under trial, augmentation with drugs
      such as lithium and triiodothyronine, and switching to other somatic therapies
      such as electroconvulsive therapy and monoamine inhibitors. Only if these
      strategies fail, should novel treatments such as the use of venlafaxine,
      antidepressant combinations and augmentation with sleep deprivation be
      considered. Experimental strategies such as the use of antiglucocorticoids and
      sex hormones, which carry considerable risk, should be restricted to research
      settings. Somatotherapy should be combined in all cases with depression-specific
      psychotherapy. Psychosurgery should be considered only in truly intractable
      cases. Rational and energetic treatment can adequately help a large majority of
      patients with treatment-resistant depression.

PMID- 9624867
TI  - Thrombopoietin: it has been cloned, therefore, it exists!

PMID- 9624868
TI  - Troglitazone: a new drug for type 2 diabetes mellitus.

PMID- 9624869
TI  - Scabies.

PMID- 9624870
TI  - Severe postpartum haemorrhage: a rational approach.

PMID- 9624871
TI  - Studying in Germany: a harrowing prospect.

PMID- 9624873
TI  - Cloning: the cataclysmic human challenge.

PMID- 9624872
TI  - Cadaveric organ transplantation in Japan--past, present and the future.

PMID- 9624874
TI  - Lady Hardinge Medical College, New Delhi.

PMID- 9624875
TI  - Indian medical research.

PMID- 9624876
TI  - Indian medical research.

PMID- 9624877
TI  - On gadgets in medicine.

PMID- 9624878
TI  - Dietary fat consumption and health.
AB  - Dietary Guidelines have emerged over the past 30 years recommending that
      Americans limit their consumption of total fat and saturated fat as one way to
      reduce the risk of a range of chronic diseases. However, a low-fat diet is not a
      no-fat diet. Dietary fat clearly serves a number of essential functions. For
      example, maternal energy deficiency, possible exacerbated by very low-fat intakes
      (< 15% of energy), is one key determinant in the etiology of low birth weight.
      The debate continues over recommendations for limiting total fat and saturated
      fatty acid intake in children. Recent evidence indicates that diets with adequate
      energy providing less than 30% of energy from fat are sufficient to promote
      normal growth and normal sexual maturation. More attention needs to be devoted to
      the effect of dietary fat reduction on the nutrient density of children's diets.
      The association between dietary fat and CHD has been extensively studied. Diets
      high in saturated fatty acids and trans fatty acids increase LDL cholesterol
      levels, and in turn, the risk of heart disease. The relationship between high
      carbohydrate/low-fat diets and CHD is more ambiguous because high-carbohydrate
      diets induce dyslipidemia in certain individuals. Obesity among adults and
      children is now of epidemic proportions in the United States. High-fat diets
      leading to excessive energy intakes are strongly linked to the increasing obesity
      in the United States. However, the prevalence of obesity has increased during the
      same time period that dietary fat intake (both in absolute terms and as a
      percentage of total dietary energy) has decreased. These trends suggest that a
      concomitant decrease in total dietary energy and modifications of other lifestyle
      factors, such as physical activity, also need to be emphasized. Obesity is also
      an independent risk factor for the development of diabetes. The current
      availability of fat-modified foods offers the potential for dietary fat reduction
      and treatment of the comorbidities associated with diabetes. However, to date,
      few studies have documented the effectiveness of fat-modified foods as part of a
      weight loss regimen or in reduction in CHD risks among individuals with diabetes
      mellitus. The association between total dietary fat and cancer is still under
      debate. While there is some evidence demonstrating associations between dietary
      fat intake and cancers of the breast, prostate, and colon, there are serious
      methodologic issues, including the difficulty in differentiating the effects of
      dietary fat independent of total energy intake. Reported total fat and saturated
      fatty acid intakes as a percentage of total energy have been declining over the
      past 30 years in the United States. Despite this encouraging trend, the majority
      of individuals--regardless of age--do not report consuming a diet that meets the
      levels of fat and saturated fatty acids recommended by the Dietary Guidelines for
      Americans. On a relative basis, saturated fat intake has gone down less than has
      total fat intake. Individuals of all ages who report consuming a diet with < or =
      30% of energy from fat consistently have lower energy intakes. Given the
      increasing rates of obesity in the United States at an earlier and earlier age,
      dietary fat reduction may be an effective part of an overall strategy to balance
      energy consumption with energy needs. In each of the age/gender groups reporting
      consumption of < or = 30% of energy from fat and less than 10% of energy from
      saturated fatty acids, fat-modified foods play a more important role in their
      diets than for people who are consuming higher levels of fat and saturated fat.
      The data are clear than fat-modified foods make a more significant contribution
      to diets of consumers with low-fat intakes. While one cannot argue cause and
      effect from the results presented, the patterns of fat-modified foods/low-fat
      intakes are consistent. The focus on overall diet quality is often lost in the
      national obsession with lowering fat inta

PMID- 9624880
TI  - Behavioral and social influences on food choice.

PMID- 9624879
TI  - Physiology of fat replacement and fat reduction: effects of dietary fat and fat
      substitutes on energy regulation.

PMID- 9624882
TI  - Recommendations: what needs to be done? Summary of the conference participants'
      small-group discussions.

PMID- 9624881
TI  - Educating consumers regarding choices for fat reduction.

PMID- 9624883
TI  - Diagnostic utility of serum transferrin receptors measurement in assessing iron
      status.
AB  - Serum transferrin receptors (TfR) are a sensitive index of tissue iron
      availability, increasing progressively in response to functional iron deficiency.
      Unlike conventional laboratory tests of iron status, serum TfR are unaffected by
      underlying acute or chronic infection. Therefore, serum TfR measurement is
      particularly promising for evaluation of iron status when iron deficiency is
      simultaneously present with overt or subclinical infection or inflammation--a
      scenario often seen in patients seeking medical care, in elderly persons, and in
      persons living in developing countries. This test is also promising for
      assessment of iron status in pregnancy because it is not confounded by
      gestational effects. With the exception of conditions associated with markedly
      enhanced erythropoiesis which can increase TfR independently (e.g., megaloblastic
      anemia, thalassemia), serum TfR determination is a specific test of iron status.
      Serum TfR measurement is also reliable; a single, small amount of blood sample is
      adequate for its accurate determination. These sensitivity, specificity, and
      reliability characteristics of serum TfR measurement enable it to enhance
      confidence in iron status assessment in complex situations with the standard
      repertoire of laboratory tests.

PMID- 9624884
TI  - The effect of minor constituents of olive oil on cardiovascular disease: new
      findings.
AB  - There has been much interest regarding the components that contribute to the
      beneficial health effects of the Mediterranean diet. Recent findings suggest that
      polyphenolic compounds found in olive oil are endowed with several biologic
      activities that may contribute to the lower incidence of coronary heart disease
      in the Mediterranean area.

PMID- 9624885
TI  - Combined calcium and vitamin D supplementation reduces bone loss and fracture
      incidence in older men and women.
AB  - A recent supplementation study of 389 men and women, over the age of 65 years was
      conducted to address the impact of combined calcium and vitamin D supplementation
      on nonvertebral fracture incidence and maintenance of bone mass. Daily
      supplementation with 500 mg calcium and 700 IU vitamin D for 3 years moderately
      reduced bone loss at several sites and significantly decreased the rate of
      nonvertebral fractures, compared with a placebo group. Optimal intake of both
      calcium and vitamin D may be an easily implemented strategy to maintain existing
      bone mass and reduce the risk of fracture in older men and women.

PMID- 9624886
TI  - Potassium and hypertension.
AB  - A recent meta-analysis supports the premise that increased potassium intake may
      play a role in the prevention and treatment of hypertension. The possible
      mechanisms by which potassium may act as an antihypertensive and recommendations
      regarding increasing potassium intake are also discussed.

PMID- 9624887
TI  - Predicting obesity in children.
AB  - Obesity in both children and adults is a major public health concern in the
      United States. Recent studies have provided data on predicting whether children
      will become obese adults. This information may be helpful in the development of
      preventive measures and treatments for obesity.

PMID- 9624888
TI  - Transport of retinoids by the interphotoreceptor retinoid-binding protein.
AB  - In the retina, the interphotoreceptor retinoid-binding protein shuttles retinoids
      between the retinal pigment epithelium and the rod outer segment. A molecular
      mechanism for this transport is proposed.

PMID- 9624889
TI  - Expanded Programme on Immunization (EPI). Progress towards global poliomyelitis
      eradication, 1988-1997.

PMID- 9624890
TI  - Hospital acquisitions of medical practices. The physician's perspective.

PMID- 9624891
TI  - Responding to a health care fraud investigation. A practice guide.

PMID- 9624892
TI  - Defending the impaired physician.

PMID- 9624893
TI  - Understanding managed care contracts.

PMID- 9624894
TI  - Quantitation of phosphorothioate oligonucleotides in human blood plasma using a
      nanoparticle-based method for solid-phase extraction.
AB  - Based on the application of cationic polystyrene nanoparticles, a novel method
      for solid-phase extraction of phosphorothioate oligonucleotides from human plasma
      has been developed. A high binding affinity, which is required for an effective
      isolation out of complex mixtures, is mediated by hydrophobic and multiple
      electrostatic interactions between the oligonucleotides and the nanoparticles.
      The principle of the method is based on a pH-controlled adsorption/desorption
      mechanism. Analysis of the extracted samples was performed by capillary gel
      electrophoresis. Extraction conditions were optimized, providing the isolation of
      oligonucleotides (> or = 10 nucleotide units) in high yields and purity even at
      concentrations in the low-nanomolar range (down to 5 nM). The low salt
      contamination of the samples allows their direct analysis by electrospray mass
      spectrometry. The combined linearity and accuracy of the assay together with
      absolute recovery rates in the range of 60-90% indicate that the developed solid
      phase extraction method is generally applicable to quantitation of
      oligonucleotides in human plasma. Further improvement was achieved with an
      optimized carrier system of 2-fold enlarged particles which reduces the time
      consumption of the extraction procedure to approximately 30 min.

PMID- 9624895
TI  - Microwave method for preparing erythrocytes for measurement of zinc concentration
      and zinc stable isotope enrichment.
AB  - A microwave digestion method to prepare human erythrocytes for measurement of Zn
      concentration by atomic absorption spectrophotometry and stable isotope
      enrichment by mass spectrometry is described. Also described is a process for
      purifying digested erythrocyte samples enriched with Zn stable isotope for
      analysis by fast atom bombardment mass spectrometry. Microwave digestion was
      investigated as a way to increase sample throughput by replacing a more time
      consuming conventional oven ashing/hot plate wet digestion method. Pooled red
      blood cells and NIST bovine liver standard reference material were digested by
      the two different methods and zinc recoveries compared by atomic absorption
      spectrophotometry. Microwave and conventional methods yielded 11.7 +/- 0.1 and
      11.7 +/- 0.2 micrograms/g (wet wt), respectively, for the pooled erythrocytes,
      and Zn recovery from NIST bovine liver standard (certified 123 +/- 8
      micrograms/g) was 128.2 +/- 1.2 and 127.4 +/- 1.3 micrograms/g, p > or = 0.282,
      respectively. Microwave digestion improved the processing of erythrocytes for
      atomic absorption spectrophotometry and mass spectrometry by reducing digestion
      time from 1 week to 2 h. In addition, a procedure for purifying digested
      erythrocyte samples by either extraction and ion-exchange chromatography in
      preparation for mass spectrometry analysis of Zn stable isotope enrichment is
      outlined.

PMID- 9624896
TI  - Iodine determination in food samples using inductively coupled plasma isotope
      dilution mass spectrometry.
AB  - Two different sample treatment methods are used in connection with inductively
      coupled plasma isotope dilution mass spectrometry for accurate and precise
      determinations of iodine traces in food samples. 129I-enriched iodate is applied
      as a spike compound for the isotope dilution step. Extraction of iodine by
      tetramethylammonium hydroxide (TMAH) solution at high temperatures in a closed
      vessel is one of the sample treatment methods. The other one is a complete
      decomposition of the sample with a mixture of perchloric acid and nitric acid
      using microwave assistance. By analyzing different certified reference materials
      (three milk powders with different iodine levels, BCR CRM 63, 150, and 151;
      bovine liver BCR CRM 185), the accuracy of ICP-IDMS with both sample treatment
      methods could be demonstrated. The relative standard deviation was typically in
      the range of 0.6-2.8% for iodine concentrations between 0.1 microgram g-1 and 5
      micrograms g-1. The detection limit was 8 ng g-1 using sample weights of 0.8 g.
      In a round robin test, using two different types of infant food samples, the
      results of the two ICP-IDMS methods and of an ICP-MS method without the isotope
      dilution technique, but applying the TMAH extraction procedure, agree very well
      with the mean of results of all participating laboratories also using ICP
      MS/TMAH. However, the ICP-IDMS method is faster, more precise, widely independent
      of matrix effects, and, therefore, relatively accurate, which makes this method
      especially attractive for use as a routine method.

PMID- 9624897
TI  - Three-dimensional ion mobility/TOFMS analysis of electrosprayed biomolecules.
AB  - An ion mobility/mass spectrometry technique has been developed to record mass
      resolved ion mobility distributions for multiple ions simultaneously. The
      approach involves a new instrument that couples an electrospray ion source to an
      injected-ion drift tube/time-of-flight mass spectrometer. Individual components
      in a mixture of ions are separated by mobility differences in a drift tube and
      subsequently dispersed by mass-to-charge ratios in a time-of-flight instrument.
      Flight times in the mass spectrometer are much shorter than residence times in
      the drift tube, making it possible to record mass-resolved ion mobilities for all
      ions simultaneously. The result is a three-dimensional spectrum that contains
      collision cross section, mass-to-charge, and ion abundance information. The
      instrument and data acquisition system are described. Examples of combined ion
      mobility/time-of-flight data are presented for distributions of electrosprayed
      bradykinin and ubiquitin ions.

PMID- 9624898
TI  - Capillary electrophoresis analysis of nitric oxide synthase related metabolites
      in single identified neurons.
AB  - Intracellular concentrations of L-citrulline (Cit) and its metabolites are
      related to nitric oxide synthase (NOS) activity, an enzyme producing the
      intercellular messenger NO in animal tissues including the nervous system. A
      capillary electrophoresis system using laser-induced fluorescence detection is
      described, and methods are developed to monitor the levels of L-arginine (Arg),
      Cit, and related molecules in identified neurons of the marine slugs,
      Pleurobranchaea californica and Aplysia californica. The limits of detection for
      Arg, Cit, L-arginino-succinate, L-ornithine, and L-arginine phosphate range from
      50 amol to 17 fmol (5 nM to 17 microM in the neurons under study); these
      detection limits are significantly lower than actual intracellular levels of the
      metabolites, allowing the direct assay of single cells. The levels of NOS
      metabolites in individual neurons varied form 6 (Arg) and 4 mM (Cit) in putative
      NOS-containing neurons down to < 1 microM (undetectable) levels in many putative
      NOS-negative cells. The Arg/Cit ratio is independent of cell volume, correlates
      with NADPH-diaphorase staining, and appears to be a characteristic parameter for
      the presence of NOS activity in identified neurons.

PMID- 9624899
TI  - Stable capillary coating with successive multiple ionic polymer layers.
AB  - A stable modification of the inner wall of a fused silica capillary was
      established by a simple coating procedure, successive multiple ionic-polymer
      layer (SMIL) coating. An anionic polymer was tightly fixed to the capillary wall
      by the SMIL coating, in which a cationic polymer was sandwiched between the
      anionic polymer and the uncoated fused silica capillary by noncovalent bonding.
      The SMIL-coated capillary showed a long lifetime. The endurance of the SMIL
      coated capillary was more than 100 runs, and it was also tolerant to organic
      solvents, 1 M NaOH, and a surfactant. The coating efficiency did not depend on
      capillary sources, and the relative standard deviation of capillary-to-capillary
      reproducibility was less than 1%. In this study, dextran sulfate (DS) was used as
      the anionic polymer, and Polybrene was used as the cationic polymer for SMIL
      modification. The DS-modified capillary (SMIL-DS capillary) exhibited a pH
      independent electroosmotic flow (EOF) from anode to cathode in the pH range of 2
      11. The SMIL-DS capillary showed good performance for acidic protein analyses
      under physiological conditions (pH 7.4). Also, the presence of EOF under acidic
      conditions permitted new applications. Simultaneous separations of cationic,
      anionic, and neutral amino acids were achieved by capillary zone electrophoresis,
      and separations of cresol isomers were achieved by micellar electrokinetic
      chromatography under the acidic conditions. The SMIL-DS capillary was also useful
      for fast and precise determination of the pKa of acidic functional groups.

PMID- 9624900
TI  - Molded rigid polymer monoliths as separation media for capillary
      electrochromatography. 1. Fine control of porous properties and surface
      chemistry.
AB  - Monolithic columns for capillary electrochromatography have been prepared within
      the confines of untreated fused-silica capillaries in a single step by a simple
      copolymerization of mixtures of butyl methacrylate, ethylene dimethacrylate, and
      2-acrylamido-2-methyl-1-propane-sulfonic acid (AMPS) in the presence of a
      porogenic solvent. The use of these novel macroporous monoliths eliminates the
      need for frits, the difficulties encountered with packed capillaries, and
      capillary surface functionalization. Since the porous properties of the
      monolithic materials can be easily tailored through changes in the composition of
      the ternary porogenic solvent, the effects of both pore size and the percentage
      of sulfonic acid monomer on the efficiency and the electroosmotic flow velocity
      of the capillary columns could be studied independently over a broad range. A
      simple increase in the content of charged functionalities within the monolith
      leads to an expected acceleration of the flow velocity. However, increasing the
      pore size leads to a substantial deterioration of the efficiency of the
      separation. In contrast, monoliths with increasing levels of AMPS in which the
      pore size remains fixed due to adjustments in the composition of the porogenic
      solvent show no deterioration in efficiency while maintaining the same increase
      in flow velocity, thus producing a significant reduction in separation time.
      Additionally, measurements on monoliths with constant levels of AMPS but
      different pore sizes suggest that flow velocity may be affected by the flow
      resistance within the capillary column.

PMID- 9624901
TI  - Molded rigid polymer monoliths as separation media for capillary
      electrochromatography. 2. Effect of chromatographic conditions on the separation.
AB  - The effect of chromatographic conditions on the performance of monolithic
      poly(butyl methacrylate-co-ethylene dimethacrylate-co-2-acrylamido-2-methyl-1
      propanesulfonic acid) columns in capillary electrochromatography has been
      studied. The flow velocity was found to be proportional to the strength of the
      electric field and both the pH and the composition of the mobile phase. A column
      efficiency of 120,000 plates/m at the optimum flow velocity of 1.5 cm/min is
      achieved for all the monolithic capillary columns of identical composition and
      porosity, regardless of their length, which varied from 30 to 120 cm. The
      polymeric separation medium exhibits retention and selectivity properties similar
      to those of typical ODS packings for reversed-phase chromatography. In addition
      to the "classical" use of monolithic capillary columns for the
      electrochromatographic separation of small molecules in reversed-phase mode,
      larger styrene oligomers were also separated under isocratic elution conditions.
      In addition, the electroosmotically driven size exclusion chromatography of
      polystyrene standards with molecular weights up to 10(6) has been demonstrated
      for the first time.

PMID- 9624902
TI  - DNA sequencing on microfabricated electrophoretic devices.
AB  - We present a model that quantitatively describes the performance of
      microfabricated electrophoretic devices filled with linear polyacrylamide as
      replaceable sieving material for single-stranded DNA analyses. The dependence of
      resolution on various separation parameters such as selectivity, diffusion,
      injector size, device length, and channel folding was investigated. A previously
      predicted dependence of longitudinal diffusion coefficient on electric field
      strength has been verified. We have used this model to develop and optimize
      microfabricated electrophoretic devices for DNA analyses. For single-color DNA
      sequencing mixtures, we routinely achieve separations of 400 bases in under 14
      min at 200 V/cm, and separation of 350 bases in only 7 min at 400 V/cm, with a
      minimum resolution of R = 0.5. Our results also indicate reduced fragment biasing
      and efficient sample stacking for DNA sample loading on microfabricated devices.

PMID- 9624903
TI  - Isolation of cultured cervical carcinoma cells mixed with peripheral blood cells
      on a bioelectronic chip.
AB  - The separation and subsequent isolation of the metastatic human cervical
      carcinoma cell line (HeLa cells) from normal human peripheral blood cells has
      been achieved by exploiting their differential dielectric properties. The
      isolation process is carried out on a silicon chip containing a five-by-five
      array of microlocations. These microlocations contain underlying circular
      platinum electrodes with 80-micron diameters and center-to-center spacing of 200
      microns. The surfaces of the electrodes and nonmetallized areas have been coated
      with a permeation layer to prevent the direct contact of cells with the electrode
      and also to minimize the nonspecific adhesion of the cells to the chip surface.
      An inhomogenous ac field is applied to the electrodes to create the conditions
      for dielectrophoretic separation of cells. Cell separation using
      dielectrophoresis as well as electronic lysis on a silicon chip would provide
      essential sample-processing steps which may be combined with a later multiplex
      electronic hybridization step in an integrated assay system.

PMID- 9624904
TI  - Coupled achiral/chiral column techniques in subcritical fluid chromatography for
      the separation of chiral and nonchiral compounds.
AB  - A multicolumn approach was developed to address the limited achiral selectivity
      of chiral stationary phases. Groups of structurally related compounds, including
      beta-blockers and 1,4-benzodiazepines, were separated using coupled
      achiral/chiral stationary phases under subcritical fluid conditions. The achiral
      selectivity of amino and cyano stationary phases was used to modify the
      resolution of compounds on a Chiralcel OD chiral stationary phase by combining
      the achiral and chiral columns in series. In the case of the benzodiazepines,
      separation of achiral compounds was performed concurrently with the
      enantioseparation of chiral molecules. The separation of components of a
      multidrug cough and cold medication was also demonstrated on a cyano column
      coupled with a Chiralpak AD chiral stationary phase. The use of modified carbon
      dioxide eluents eliminated the mobile phase incompatibility problems associated
      with column coupling in liquid chromatography and incorporated the high
      efficiency of sub- and supercritical fluid chromatography.

PMID- 9624905
TI  - Narrow-bore HPLC in combination with fluorescence and electrospray mass
      spectrometric detection for the analysis of cocaine and metabolites in human
      hair.
AB  - A simple, but sensitive and specific, high-performance liquid chromatographic
      assay for cocaine, cocaethylene, and benzoylecgonine is described. Using direct
      fluorometric detection, the procedure is particularly interesting for the routine
      analysis of human hair samples. In the sample preparation part, the hair samples
      are cut and washed and two internal standards with close structural resemblance
      to benzoylecgonine and cocaine as well as to cocaethylene are added.
      Subsequently, the hair samples are homogenized, hydrolyzed overnight in a 0.1 M
      HCl solution at 56 degrees C, and extracted on IST Confirm HCX solid-phase
      extraction columns. Chromatographic separation is achieved on a narrow-bore
      Hypersil BDS C18 column (125 x 2.1 mm, 3 microns) by gradient elution with an
      ammonium acetate buffer-methanol/acetonitrile mixture. For the fluorometric
      detection, excitation and emission wavelengths of 242 and 315 nm, respectively,
      are used. This analysis protocol affords a method of high sensitivity and
      specificity which has been fully evaluated and validated. The data presented show
      good accuracy and linearity with excellent reproducibility and recovery. Because
      unequivocal identity confirmation is mandatory in forensic applications, an
      extension of the analysis protocol was accomplished toward mass spectrometric
      detection. We succeeded in a simple methodological transfer from LC/FL to LC/ESI
      MS/MS, thus providing two complementary approaches after a single, common sample
      processing step. Hair samples from 29 fatalities, all known drug users and
      suspected victims from a drug overdose, were analyzed in this way. Of the
      investigated samples, 12 were positive and the concentrations found range from
      0.98 to 938 ng/mg of hair for cocaine and from 1.45 to 388 ng/mg of hair for
      benzoylecgonine. Traces of cocaethylene were also found in two of the hair
      samples. The results obtained with LC/ESI-MS/MS were in close agreement with
      those obtained with LC/FL, positively confirming the isolates' identity and
      structure by means of the resulting MS/MS spectra.

PMID- 9624906
TI  - An assay method for evaluating chemical selectivity of agonists for insulin
      signaling pathways based on agonist-induced phosphorylation of a target peptide.
AB  - An optical method for evaluating the physiologically relevant agonist and
      antagonist selectivity of an insulin signaling pathway based on an insulin
      dependent on/off switching of phosphorylation of a target peptide via insulin
      receptor is described. Insulin receptor serves as a binding for insulin and a
      given insulin receptor-binding peptide as a target for an insulin-receptor
      complex. Upon binding of insulin to its receptor, the insulin receptor undergoes
      autophosphorylation which enables the receptor to have a kinase activity and
      phosphorylate various substrates. The phosphorylated tyrosine in the substrate
      was measured with a monoclonal anti-phosphotyrosine antibody. As the target
      substrate for insulin receptor, a Y939 peptide consisting of 12 amino acid
      residues derived from insulin receptor substrate 1 (IRS-1) was used. The present
      assay method involves different sequential steps: (1) immobilization of a biotin
      coupled Y939 peptide on an avidin coated 96-well plate via biotin-avidin
      complexation; (2) insulin-dependent phosphorylation of the Y939 peptide by the
      insulin receptor; (3) enzymatic reaction and absorptiometric assay of the
      phosphorylated Y939 peptide using the anti-phosphotyrosine antibody labeled with
      horseradish peroxidase. An insulin-dependent absorbance was observed for insulin
      concentrations from 1.0 x 10(-10) to 1.0 x 10(-7) M, and it leveled off. The
      observed absorbance was explained to be due to an increase in the phosphorylated
      Y939 peptide caused by insulin and its receptor complexation. No signal was,
      however, induced by both vanadyl and vanadate ions at concentrations up to 1.0 x
      10(-4) M; these results and previous intact cell level data taken together led to
      the conclusion that these ions did not induce phosphorylation of the Y939
      peptide. Upon addition of tyrphostin 25, a specific inhibitor for insulin
      receptor kinase activity, phosphorylation of the Y939 peptide in the presence of
      1.0 microM insulin was competitively inhibited over 1.0 x 10(-4) M tyrphostin 25.
      The present system thus exhibited "physiologically more relevant" agonist and
      antagonist selectivity, the principle of which is based in part on the insulin
      signal transduction rather than simply relying on the binding assay. The
      potential use of the present method for evaluating the selectivity of a wide
      range of agonists and antagonists toward the insulin signaling pathways is
      discussed.

PMID- 9624908
TI  - Flow injection monitoring of aflatoxin M1 in milk and milk preparations using
      filter-supported bilayer lipid membranes.
AB  - This work describes a technique for the rapid and sensitive electrochemical flow
      injection monitoring of aflatoxin M1 (AFM1) using stabilized systems of filter
      supported bilayer lipid membranes (BLMs). Injections of AFM1 were made into
      flowing streams of a carrier electrolyte solution, and a transient current signal
      with a duration of seconds reproducibly appeared less than 10 s after exposure of
      the lipid membranes to the toxin. The magnitude of this signal was linearly
      related to the concentration of AFM1, with detection limits at the subnanomolar
      level. The mechanism of signal generation was investigated by differential
      scanning calorimetric experiments. The technique was applied for the rapid flow
      injection determination of AFM1 in milk and milk preparations. The effect of
      potent interferences such as proteins and lipids was investigated, and the
      results show that interferences from these milk constituents can be eliminated by
      modulation of the flow rate of the carrier solution so as not to allow adsorption
      of these compounds in BLMs. AFM1 could be determined in continuous flowing
      systems with a rate of at least 4 samples min-1. Repetitive cycles of injection
      of AFM1 showed no signal degradation during each cycle.

PMID- 9624907
TI  - Determination of 226Ra in mineral drinking waters by alpha liquid scintillation
      with rejection of beta-gamma emitters.
AB  - The radiotoxicity of radium isotopes (especially the long-half-life 226Ra)
      requires their monitoring in drinking waters or nuclear wastes. We studied the
      applicability of the PERALS method of detection (photon electron rejecting alpha
      liquid scintillation) for radium measurement. This method combines alpha liquid
      scintillation with pulse shape analysis for beta rejection and specific chemical
      extractants included in the scintillating cocktail. Radium is separated by an
      extractive-scintillator cocktail called RADAEX containing 2-methyl-2
      heptylnonanoic acid (HMHN) and dicyclohexano-21-crown-7 (Cy(2)21C7) as extractant
      molecules. The variation of the radium extraction has been studied relative to
      pH, salt concentrations, anion and cation effects, and the volume ratio between
      aqueous and organic phases. The main parameter affecting the radium extraction in
      mineral drinking water is its complexation by inorganic anions, especially
      sulfate. Due to the lack of thermodynamic data, some complexation constants had
      to be determined. For instance, the value reported in this paper for radium
      sulfate (log beta = 2.58 +/- 0.22) is in good agreement with that from the
      literature. The knowledge of complexation constants allows the determination of
      radium extraction recovery for any solution when the inorganic anion
      concentrations had been measured by capillary zone electrophoresis. The detection
      limit for this technique is found to be equal to 0.006 Bq.L-1 using only 6 mL of
      sample solution for analysis. Several French mineral waters have been studied and
      the results compared with determinations of uranium and thorium concentrations by
      ICPMS and time-resolved laser induced fluorescence (TRLIF).

PMID- 9624909
TI  - Immunomagnetic separation with mediated flow injection analysis amperometric
      detection of viable Escherichia coli O157.
AB  - The coupling of an immunological separation (using immunomagnetic beads) with
      amperometric flow injection analysis detection of viable bacteria is presented.
      Using a solution containing Escherichia coli O157, the electrochemical response
      with two different mediators [potassium hexacyanoferrate(III) and 2,6
      dichlorophenolindophenol] was evaluated in the FIA system. Antibody-derivatized
      Dynabeads were used to selectively separate E. coli O157 from a matrix. The
      kinetics and the capacity parameters regarding the attachment of bacteria to the
      immunobeads were studied. The immunomagnetic separation was then used in
      conjunction with electrochemical detection to measure the concentration of viable
      bacteria. A calibration curve of colony-forming units (cfu) against
      electrochemical response was obtained. The detection limit for this rapid
      microbiological method was 10(5) cfu mL-1, and the complete assay was performed
      in 2 h. Some advantages over ELISA methods are the direct detection of viable
      cells (and not total bacterial load) and the need for only one antibody (not
      enzyme-labeled), thus making the assay faster (only one washing step is
      necessary) and less expensive.

PMID- 9624910
TI  - Platinum-catalyzed enzyme electrodes immobilized on gold using self-assembled
      layers.
AB  - The bonding of enzymes to self-assembled monolayers (SAMs) of alkanethiols onto
      gold electrode surfaces is exploited to produce an enzyme biosensor. The
      attachment of glucose oxidase to a SAM of 3-mercaptopropionic acid was achieved
      using carbodiimide coupling. The resultant biosensor showed good sensitivity to
      glucose and a large dynamic range when measured amperometrically via the p
      benzoquinone mediator. On the other hand, subsequent platinization of the enzyme
      SAM electrode allowed hydrogen peroxide produced in the enzyme reaction to be
      detected directly, thus obviating the need for an artificial redox mediator. The
      performance of such sensors constructed on bulk gold electrodes was evaluated and
      finally compared to that of some preliminary thin-film gold electrodes.
      Biosensors constructed using the two alternative electrode surfaces have quite
      different sensitivities, thus reflecting the influence of the anchoring surface
      on the performance of the biosensor.

PMID- 9624911
TI  - Assay for cephapirin and ampicillin in raw milk by high-performance liquid
      chromatography--integrated pulsed amperometric detection.
AB  - The FDA has issued guidelines governing the use of antibiotics in cattle and
      routinely tests for the presence of antibiotics in milk. Unfortunately, these
      compounds are often difficult to detect by direct methods because they often lack
      a chromophore or fluorophore. Integrated pulsed amperometric detection (IPAD)
      following reversed-phase liquid chromatography is well-suited for this analysis
      because it is selective, sensitive, and direct; i.e., derivatization is not
      required. This work involves the development of a simple, rapid assay for the
      determination of beta-lactam antibiotic residues in milk using HPLC-IPAD,
      specifically, ampicillin and cephapirin. Since the analyst studied here are
      detectable by UV detection, a comparison between IPAD and UV detection will be
      made. Sample preparation schemes that involve the extraction of antibiotics of
      interest from the milk matrix and subsequent cleanup are an important aspect of
      this project. These procedures will be discussed in detail. In addition,
      analytical figures of merit and IPAD wave form optimization will be addressed.

PMID- 9624912
TI  - What you need to know about strokes.

PMID- 9624913
TI  - Irregular beats: nuisance or danger?

PMID- 9624915
TI  - Do high heels lead to arthritis of the knee?

PMID- 9624914
TI  - Viagra: an option, not a miracle.

PMID- 9624916
TI  - Back pain and spinal fractures.

PMID- 9624917
TI  - High-altitude headache.

PMID- 9624918
TI  - Cancer "breakthrough" is still in the future.

PMID- 9624919
TI  - Yoga-like breathing for heart failure.

PMID- 9624920
TI  - Ulcer causes: genes plus germs.

PMID- 9624921
TI  - Must people with normal BP go low salt?

PMID- 9624922
TI  - Pulmonary embolism. What you know may save your life.

PMID- 9624923
TI  - Health tips. Medical information in an emergency.

PMID- 9624924
TI  - FDA approves impotence pill.

PMID- 9624926
TI  - Hearing aids. Advances in design improve sound quality.

PMID- 9624925
TI  - Study shows controversial prostate drug is beneficial.

PMID- 9624927
TI  - Achilles tendon. When a wrong move results in a rupture.

PMID- 9624928
TI  - Healthful barbecuing. Avoiding the pitfalls.

PMID- 9624929
TI  - I've been diagnosed with heart failure, and now my doctor wants me to have an
      exercise stress test. Why? Couldn't this be dangerous?

PMID- 9624930
TI  - I have chronic pain from arthritis but can't take aspirin or ibuprofen because of
      the side effects. Plain Tylenol doesn't give me enough relief. I've heard of a
      drug called Ultram. Could it help?

PMID- 9624931
TI  - I'm thinking of getting a hearing aid. If I have hearing loss in both ears, do I
      need two hearing aids?

PMID- 9624932
TI  - The overlap between the practice of medicine and the practice of nursing.

PMID- 9624934
TI  - Information technology: meet the challenge.

PMID- 9624933
TI  - Getting politically involved.

PMID- 9624935
TI  - HCFA issues 1998 anesthesia Medicare conversion factors: anesthesia services
      receive 2.1% payment increase.

PMID- 9624936
TI  - A report on the Council on Certification 1996 Professional Practice Analysis.
AB  - The purpose of this article is to provide an overview of the Council on
      Certification of Nurse Anesthetists 1996 Professional Practice Analysis. This
      analysis was used to update the previous content validation studies. Surveys were
      mailed to a select group and a practitioner group of 2,859 Certified Registered
      Nurse Anesthetists with a response rate of 63.7%. Respondents were asked survey
      questions related to demographics, practice settings, education, and fundamental
      knowledge related to nurse anesthesia practice. Respondents were asked for the
      frequency and level of expertise related to patient conditions, procedures,
      anesthesia agents and techniques, equipment, instrumentation, and technology of
      anesthesia practice. The results for both groups were consistent with the
      previous studies. The Rasch rating scale model was used to transform the results
      from ordinal data onto a linear, equal-interval scale. Members of the Council on
      Certification of Nurse Anesthetists carefully reviewed all of the Professional
      Practice Analysis results and voted to maintain the current test blueprint and
      percentage of test items in each area.

PMID- 9624937
TI  - AANA Journal course: update for nurse anesthetists--diabetes mellitus: overview
      and current concepts in anesthetic management.
AB  - Diabetes mellitus is one of the more common endocrine disorders encountered in
      the anesthetic management of surgical and obstetrical patients. These patients
      often have complications associated with the disease process which may increase
      perioperative morbidity and mortality. Optimal management depends upon an
      understanding of the disease process as well as special considerations unique to
      the diabetic. This AANA Journal course reviews the pathophysiology of diabetes
      and common complications associated with the disease. Perioperative
      considerations include assessment and metabolic control during the time of
      surgical stress. In concludes with acute complications and their recognition and
      management.

PMID- 9624938
TI  - Assessing sensory blockade with alcohol and pinprick after subarachnoid block.
AB  - The purpose of this study was to determine the accuracy of alcohol swabs in
      assessing dermatome levels in comparison to pinprick after subarachnoid block.
      Room temperature alcohol swabs and pinprick were used to determine dermatome
      levels at 5, 10, and 15 minutes after a 15-mg hyperbaric bupivacaine subarachnoid
      block was administered with the patient in the sitting position. The sample
      population consisted of 53 men scheduled for elective transurethral resection of
      the prostate or bladder tumor with an ASA classification of I to IV. Subjects
      were assessed while they were in the preoperative holding area for the ability to
      discriminate pinprick and cold sensation. Data were analyzed using the Wilcoxon
      signed rank test. There was a statistically significant difference between
      alcohol and pinprick at the 10- and 15-minute assessments. (P < .05).

PMID- 9624939
TI  - A review of regional blocks for the foot.
AB  - The blocking of the posterior tibial, sural, saphenous, superficial peroneal, and
      the deep peroneal nerves with possible alternative approaches is discussed.
      Digital blocks, Mayo blocks, and intravenous regional anesthesia are also
      discussed. The placement of the tourniquet above the ankle but below the calf
      muscles will avoid deep muscle pain. Lidocaine and bupivacaine cause
      vasodilatation in the foot.

PMID- 9624940
TI  - Ascaris lumbricoides: a case report.
AB  - This is a case presentation of a multiple trauma patient who was infested with
      Ascaris lumbricoides, a roundworm. The infestation was undiagnosed until after
      extubation. Intraoperative anesthesia was uneventful and the patient was
      discharged 7 days after admission.

PMID- 9624941
TI  - Informed consent: an overview.
AB  - The patient, as a health care consumer, has a fundamental right to determine what
      shall be done to his or her own body. The doctrine of informed consent has
      evolved to protect that right. This article represents a review of the literature
      regarding the informed consent process in medicine, with an emphasis on consent
      for anesthesia. A brief history of informed consent is provided, as well as
      discussion of the controversies surrounding the topic. Several court cases are
      cited, and the opinions of various authors reflect the wide range of legal and
      ethical implications associated with informed consent.

PMID- 9624942
TI  - Professional autonomy.
AB  - Professional autonomy may represent the first step to implementing measures that
      will allow CRNAs to attain a level of independent practice consistent with their
      clinical and educational training. Autonomy is regarded as an essential
      ingredient of professionalism and confers independent function at the individual
      practitioner level. The principle of autonomy refers to the individual's capacity
      to make independent decisions based on the assumption that he or she possesses
      the cognitive, psychological, and emotional faculties to make rational decisions.
      Nursing practice meets the first two criteria of professionalism--competence and
      dedication to an important social good. The third criterion of professionalism,
      autonomy, has been a focal point for controversy since the late nineteenth
      century, in which obedience to supervisors and physicians remained a central
      focus of nursing ethics teaching until the advent of feminism in the 1970s. This
      article presents a thorough analysis of these concepts with some thoughts on how
      understanding the fundamental precepts and further research may not only help
      maintain the current level of CRNA professional autonomy but serve to guide us to
      become more autonomous in the future.

PMID- 9624943
TI  - A continuing postoperative complication: nausea and vomiting--who is affected,
      why, and what are the contributing factors? A review.
AB  - Outpatient surgery has become increasingly popular. Technical advances in both
      surgery and anesthesia have made the practice of ambulatory surgery safe and
      attractive. However, vomiting remains one of the most common postoperative
      complications. The valid patient complaint of postoperative nausea and vomiting
      has been shown to significantly delay discharge from the recovery area after
      ambulatory surgery. This article reviews the numerous factors that have been
      identified as fostering the postoperative complication of nausea and vomiting.

PMID- 9624944
TI  - A postanesthetic care charge nurse's perspective of postoperative verbal report
      by anesthesia providers.

PMID- 9624945
TI  - Quarterly update.

PMID- 9624946
TI  - SvO2 monitoring: tool for evaluating patient outcomes.
AB  - Current technology provides a simple and reliable method for continuous
      monitoring of mixed venous oxygen saturation (SvO2). Assessment of this value
      represents an important vital sign for oxygen supply and demand balance for the
      critical care patient. Nurses can use SvO2 monitoring to assess outcomes of
      therapy.

PMID- 9624947
TI  - Responding to tricyclic antidepressant overdose.
AB  - Tricyclic antidepressant overdose produces rapid multisystem complications for
      the patient. Treatment of the patient requires careful assessment and aggressive
      nursing interventions in order to produce a positive outcome.

PMID- 9624948
TI  - The prognosis for women after an acute myocardial infarction: recommendations for
      practice.
AB  - Women have different needs than men after a myocardial infarction. Therefore,
      nursing care for women should be based on current research rather than research
      based on findings using the "male model." This article examines research on the
      prognosis for women after a myocardial infarction and recommends practice changes
      for the critical care nurse based on these findings.

PMID- 9624949
TI  - Cyanide ingestion: preventing the cascade.
AB  - Patients with cyanide exposure present a rare and unique challenge to the
      critical care nurse. The following article assists the critical care nurse and
      advanced practice nurse in understanding the pathophysiology of cyanide exposure,
      assessment of signs and symptoms, and antidotal and supportive therapies. In
      addition, a case review of nursing care for a patient exposed to cyanide is
      discussed.

PMID- 9624950
TI  - A QI project to reduce nosocomial blood loss.
AB  - Nosocomial blood loss in the intensive care setting can be significant and even
      lead to anemia. The Quality Improvement (QI) Project described in this article
      resulted in standards to decrease the volume of blood loss related to laboratory
      testing in critically ill patients.

PMID- 9624951
TI  - Family coping during critical illness.
AB  - While some family members of critically ill patients effectively manage the
      stress of critical illness, others invoke coping responses that are ineffective
      and hinder patients' recovery. Critical care nurses and advanced practice nurses
      can enhance positive coping strategies of family members. This study examines the
      use and effectiveness of coping responses of family members. Strategies are
      suggested to facilitate effective coping of family members during the crisis of
      critical illness, including family attendance during invasive procedures and
      resuscitation efforts.

PMID- 9624952
TI  - Toward a holistic view of genetic technology as a way of knowing.
AB  - Technology changes the face of science and, ultimately, nature. How do we as
      nurses come to know technology? Nurses' ways of knowing, as described by Carper,
      help nurses better understand technology as a way of knowing; that is, using
      empirical, ethical, personal, and esthetic ways of knowing provides a means to
      incorporate technology into holistic nursing practice. Knowledge of technology
      also requires considering clients' and families' multiple facets of knowing. The
      article summarizes the nature of technology, nurses' ways of knowing in the
      context of genetic technology, and the rationale for understanding clients' and
      families' ways of knowing.

PMID- 9624953
TI  - Genetic predisposition testing for cancer: effects on families' lives.
AB  - Genetic testing to identify a predisposition to the development of cancer affects
      not only the person undergoing DNA analysis but also his or her entire family.
      Multiple complex issues arise in conjunction with the clinical application of
      this new tool for assessing cancer risk. Counseling families regarding genetic
      risk is multifaceted and requires genetic knowledge that may go beyond the
      expertise of the health care provider. The article describes the psychosocial
      effects of cancer predisposition testing on families, ethical and social concerns
      of cancer risk testing, and implications for nurses in counseling individuals and
      families considering predisposition testing.

PMID- 9624954
TI  - Comfort care interventions in a preimplantation genetic testing program.
AB  - The fields of human genetics and assisted reproductive technology (ART) have
      experienced many scientific advances over the past 50 years. The integration of
      these two clinical specialties has resulted in the ability to perform
      preimplantation genetic testing (PGT) on an embryo created through ART. This is a
      technology that can be used by individuals at risk for the transmission of a
      genetic disorder to prevent occurrence of the disorder in their child. Both the
      process of PGT and the life experiences that lead to the decision to use PGT
      stimulate many levels and types of discomfort. Holistic comfort care
      interventions performed by the nurse are uniquely designed to eliminate or reduce
      discomfort and to enable those at risk to utilize the available technologies to
      create healthy families.

PMID- 9624955
TI  - Genetics and community health nursing.
AB  - Genetic discoveries affect the practice of community health nurses. These nurses
      identify groups at risk for genetic diseases and participate in newborn
      screening, carrier detection testing, and presymptomatic genetic testing
      programs. Community health nurses also provide direct nursing care to individuals
      with genetic disorders. Protecting clients from harmful use of genetic
      information, planning and implementing genetic screening programs, and
      identifying genetic resources are essential components of the community health
      nurse's role.

PMID- 9624956
TI  - Implications of genetic testing of children and adolescents.
AB  - Advances in genetic technology increase the ability to test children and
      adolescents for late-onset conditions, disease susceptibilities, and carrier
      status. Genetic tests may offer medical or psychologic benefits but may also
      create harm; alteration of the child's self-concept or parent-child bonds and
      risk of stigmatization are examples of the latter. The article examines
      developmental theories concerning children's ability to make choices as well as
      informed consent and ethical considerations in genetic testing. Because optimal
      care requires awareness of the complex psychosocial and ethical issues involved
      in childhood genetic testing, nurses must be prepared to acknowledge and discuss
      such issues with families.

PMID- 9624957
TI  - Families caring for children with fetal alcohol syndrome: the nurse's role in
      early identification and intervention.
AB  - Alcohol is a teratogenic substance that, when ingested during pregnancy, may
      cause the fetus to be born with a condition known as fetal alcohol syndrome
      (FAS). FAS is a life-long condition that leads to serious primary and secondary
      disabilities. Holistic early identification and intervention for children with
      FAS and their families may ameliorate the secondary disabilities associated with
      FAS. Nurses working with families and young children could play a key role in
      early identification and intervention for children with FAS.

PMID- 9624958
TI  - Fibromyalgia and chronic fatigue: the holistic perspective.
AB  - Fibromyalgia syndrome (FMS) and chronic fatigue syndrome (CFS) are not new
      conditions, but they are receiving more attention as more research is conducted.
      These two conditions are primarily women's health problems. In some instances,
      there may be a genetic predisposition for these conditions. The impact of FMS and
      CFS can be devastating both physically and emotionally. The treatment plan must
      be interdisciplinary and holistic and include alternative therapies if the client
      and family are to be truly supported and helped in coping with these chronic
      conditions.

PMID- 9624959
TI  - Storytelling: a holistic foundation for genetic nursing.
AB  - The article discusses the need for a paradigm shift in how genetic nurses think
      about genetic information and genetic testing. It conceptualizes a theoretical
      model to depict the relationships among storytelling, holism, and genetic nursing
      practice. Four themes are discussed to explain why storytelling is necessary for
      clinical genetics: knowing the patient as a whole person, honoring the
      preciousness of personhood and the essence of humanness, uncovering power
      imbalances that inhere in therapeutic relationships, and listening to people's
      values and beliefs that affect decision making. The benefit of storytelling for
      developing and disseminating knowledge in genetic nursing is examined.

PMID- 9624960
TI  - A multiplicity of roles for genetic nursing: building toward holistic practice.
AB  - Nursing's unique contribution to human genetics is holism. There are many roles
      for basic and advanced practice nurses involved in genetics. Describing these
      roles makes it easy for nurses to learn more about genetic nursing and helps
      promote collaboration among professionals. Education for nurses about genetics
      helps foster greater nursing participation in human genetics. The goal is for
      nurses to be informed about genetics so that they can better understand people as
      whole persons whose growth and development, human response patterns, and
      biopsychosocial processes are affected by and have an effect on human DNA.

PMID- 9624961
TI  - A compassionate response toward providing. Nutrition and hydration in vulnerable
      populations.
AB  - Ethical guidelines provide a valuable first step in thinking about a new model of
      caring--one that brings together an enhanced model of patient autonomy, a clearer
      understanding of the moral (as opposed to merely biologic) meaning of life and
      death, a consistent concern for human life, and a recovery of the gerontological
      nurse practitioner's role as advocate, counselor, educator, and healer of the
      human spirit. Instead of creating a slippery slope, the emerging consensus will
      place decisions to withhold or withdraw fluids and nutrition on even firmer
      ethical, legal, and moral ground. Even in cases involving severe and enduring
      illness, disability, and "helplessness," society's focus must be on life. By its
      very nature, every human life, without reference to its condition, has a value
      that no one rightfully can deny or measure. Recognition of that truth is the
      cornerstone on which American law is built. Society's acceptance of that
      fundamental principle explains why, from time immemorial, society through law has
      extended its protection to all, including, especially, its weakest and most
      vulnerable members (Brophy v. New England Sinai Hospital., Inc., 1986).

PMID- 9624962
TI  - Incorporating simple reminiscence techniques into acute care nursing practice.
AB  - Under normal circumstances, individuals perceive the world around them in terms
      of overlapping--interacting past, present, and future time orientations. When
      individuals experience overwhelming stress, normal coping skills cease to be
      effective and this time orientation schema has a tendency to disorganize into its
      constituent spheres. The overlap and interaction of the spheres disappears.
      Individuals focus exclusively on the present sphere and lose the abilities to use
      coping skills which were successful in the past and to make reasonable
      projections about the future. Simple Reminiscence, an activity in which
      individuals look back at past experiences which they perceive as positive and
      meaningful, is one nursing intervention that RNs can use to help the client
      reclaim an effective past, present, future time orientation. Questioning the
      client about past experiences, effectively listening to what the client has to
      say, and using effectual time management skills are some techniques which RNs can
      use to incorporate Simple Reminiscence interventions into acute care nursing
      practice. These interventions will encourage the client to perceive stressful
      situations in terms of overlapping past, present, and future time spheres and
      consequently cope more effectively with stress.

PMID- 9624963
TI  - Assessment of depression in a population at risk ... newly admitted nursing home
      residents.
AB  - Depression in newly admitted nursing home residents is a frequently overlooked
      area of nursing concern. Educating staff to systematically use a standardized
      depression assessment protocol with all newly admitted residents would facilitate
      efforts to enhance the quality of residents' lives by identifying depression so
      that prompt treatment is possible. Other previously admitted residents who appear
      to be particularly vulnerable to depression would also benefit from this
      assessment. The use of this protocol for the assessment of depression offers the
      possibility of providing more accurate and more comprehensive information
      regarding mood states than that currently being documented in the Minimum Data
      Set.

PMID- 9624964
TI  - Gender differences in health and health actions among community-dwelling elders.
AB  - This secondary analysis of data from a study of elders' health examined gender
      differences in the psychological and physical health and the health actions made
      in response to specific physical complaints in a random sample of 491 community
      dwelling older adults (mean age of 75.3 years). Significant gender differences in
      anxiety, depression, and body awareness were found, although there were no
      differences in self-assessed health or total number of health problems reported.
      There were some gender differences in the types of health problems experienced.
      Subjects tended to use self-care actions, particularly over-the-counter
      medications and home remedies, more so than professional consultation. Different
      patterns of care emerged for women and men, with women somewhat more inclined to
      use self-care and men more likely to seek professional consultation.

PMID- 9624965
TI  - Increasing staff satisfaction. The impact of SCUs and family involvement.

PMID- 9624966
TI  - The therapeutic effects of Tai Chi for the elderly.

PMID- 9624967
TI  - Chronic pain in older adults. A quality of life issue.

PMID- 9624968
TI  - Alternative approaches.

PMID- 9624969
TI  - Age-related macular degeneration.
AB  - Age-related macular degeneration (AMD) is one of the leading causes of legal
      blindness among older adults. Early recognition of AMD is important because
      treatment can enable patients to maintain central vision longer. Nurses who
      understand the effects of AMD can teach their elderly patients ways to slow its
      progression, such as increasing consumption of carotenoids in their diet, wearing
      ultraviolet protective lenses, and not smoke or drink to excess. They can also
      teach them coping strategies, such as use of low visual aids, and assist them in
      making necessary adjustments to daily living as long as possible.

PMID- 9624970
TI  - Glaucoma: what the nurse practitioner should know.
AB  - Glaucoma is both an international and a national public-health issue. Worldwide,
      glaucoma is one of the leading causes of blindness. Although more than two
      million people in the United States have glaucoma, yet only half of them are
      aware that they have the disease. The diagnosis of glaucoma requires an extensive
      ocular examination. Glaucoma consists of a group of ocular diseases that result
      in optic disk cupping and visual field loss. Although glaucoma is a blinding
      disease, in most cases, blindness may be prevented through early detection and
      treatment. Glaucoma management is determined by the type of glaucoma one has.

PMID- 9624971
TI  - Diabetic retinopathy.
AB  - This article describes and differentiates between the two primary forms of
      diabetic retinopathy, specifically, background and proliferative retinopathies.
      Current therapeutic treatment modalities are discussed in detail. Signs and
      symptoms that might prompt urgent referral by the nurse practitioner are
      overviewed and appropriate patient education strategies to foster optimal
      understanding and outcomes are discussed.

PMID- 9624972
TI  - Aging, physiology, and vision.
AB  - This article provides an overview of the normal, physiologic changes in vision
      that are a part of the aging process. Associated symptoms noted by and worrisome
      to many patients also are discussed. Clear explanations of the rationale and
      cause of these concerning complaints reduces anxiety and enables people to
      function more safely in environments in which visual loss is likely to have a
      deleterious effect. Likewise, accurate understanding of normal versus
      pathological vision symptoms assists health care providers, such as nurse
      practitioners, to better triage, assess, and treat ophthalmic-related problems.

PMID- 9624973
TI  - The normal range.

PMID- 9624974
TI  - Outside the walls of the hospital.

PMID- 9624975
TI  - United States health care industry.

PMID- 9624976
TI  - Building partnerships with physicians: moving outside the walls of the hospital.
AB  - Fostering open dialogue, listening, and promoting healthy lifestyles will build
      solid relationships between physician staff and management. Solid relationships
      will reduce physician burnout and ultimately, keep a safe and happy productive
      environment that provides quality health care delivery during ever increasing
      demands for workplace change.

PMID- 9624977
TI  - Community health collaboration models for the 21st century.
AB  - The development of partnerships with physicians and other health professionals is
      a key strategy to improving the community's health. This article reviews the role
      of nurse leaders as advocates for health care improvement and leading community
      improvement efforts.

PMID- 9624979
TI  - Looking beyond the walls.
AB  - How patient care will be provided as inpatient numbers continue to decline,
      presents a challenge to the nurse executive. Looking beyond the boundaries of the
      health care facility, and developing partnerships with physicians and the
      surrounding community will position the nurse executive to move forward in the
      health care arena.

PMID- 9624978
TI  - University of Miami/Jackson Memorial Medical Center restructures its health care
      system for the 21st century.
AB  - Change, challenge, and commitment motivate staff at the University of
      Miami/Jackson Memorial Medical Center in Miami, Florida, to prepare its health
      care system for the 21st century. Doctors, nurses, environmental workers,
      pharmacists, cashiers, nursing assistants, laboratory technologists, and many
      others are participating on a variety of teams to bring about the changes needed
      for our delivery system to be competitive.

PMID- 9624980
TI  - Management service organizations: effective strategy to assume and manage full
      risk agreements?
AB  - A management services organization (MSO) has emerged as one structure to manage
      professional and hospital risk agreements. Health plans and direct payers are
      transferring traditional functions to medical groups and health systems under
      these agreements. How does a hospital and affiliated medical group develop a
      strategy to assume, manage, and mutually benefit from these agreements? When do
      market forces dictate whether an MSO is the most appropriate organizational model
      to utilize? The development of an MSO can offer an effective organizational
      strategy to capture capitated contracts and assume responsibility for population
      based medical services. This article explores the features of such an
      organization, areas for potential collaboration between the medical group and
      hospital, as well as the impact on patient care.

PMID- 9624981
TI  - High tech meets high touch: telemedicine's contribution to patient wellness.
AB  - Telemedicine is potentially an important feature of the continuum of care for the
      21st century. It saves time, money, and energy for providers and patients, but is
      largely unreimbursed by third-party payers, and faces significant legal and
      attitudinal barriers. This article explores the major elements that support and
      hinder telemedicine as a viable option for patient care services. Barriers
      reimbursement, attitudes, infrastructure, and training-must be offset by positive
      factors such as industry sponsorship of telemedicine equipment, positive clinical
      outcomes, and cost savings if implementation rates are to increase. Suggestions
      are made to nurse administrators who seek to pursue implementation of
      telemedicine technology.

PMID- 9624982
TI  - Bridging the nursing-physician gap: technology's role in interdisciplinary
      practice.
AB  - Nurses and physicians are different--in the ways they practice, think, and in the
      information systems they use. But managed care and such concomitant features as
      care teams, cost control, outcomes management, and the move from a "Medical
      Model" to a "Wellness Model," are closing the gap between the two. This article
      will explore some of the traditional differences between the two disciplines and
      the problems they present. It will also discuss some of their shared expertise,
      how managed care is contributing to this overlap and how information systems are
      evolving and must continue to do so to support the new synergies.

PMID- 9624983
TI  - Nurse practitioners' use of nursing diagnoses.

PMID- 9624984
TI  - Nursing theories and nursing diagnoses: how are they related?

PMID- 9624985
TI  - A validation study using the case-control method of the nursing diagnosis high
      risk for aspiration.
AB  - PURPOSE: To develop further the nursing diagnosis risk for aspiration by
      determining risk factors present in patients who aspirated. METHODS: The case
      control design was used to compare cases (n = 131) and controls (n = 206) on past
      and present exposures thought to be risk factors for aspiration. Data were
      analyzed using univariate and multiple logistic regression. FINDINGS: The
      following risk factors were statistically significant and comprise the final
      model: altered level of consciousness, metoclopramide (known to accelerate
      gastric emptying), vomiting, seizures, and unable to change own position.
      CONCLUSIONS: The risk factors of altered level of consciousness and delayed
      gastric emptying are currently included in the NANDA taxonomy for the nursing
      diagnosis risk for aspiration. These risk factors are not included in the
      taxonomy: vomiting, seizures, and unable to change own position. Results of the
      study have been submitted to the Diagnosis Review Committee for consideration to
      further develop this diagnosis.

PMID- 9624986
TI  - You make the diagnosis. Case study: integration of the Neuman Systems Model with
      the theory of nursing diagnosis in postpartum nursing.

PMID- 9624987
TI  - Concept analysis of relating: a human response pattern.
AB  - TOPIC: An investigation of relating, one of the nine human response patterns,
      used as the conceptual basis for the classification of nursing diagnoses.
      PURPOSE: A formal linguistic analysis of each of the nine human response patterns
      is warranted in order to allow a continuation of the exploration, definition, and
      development of research-based practice based on the NANDA framework. SOURCE:
      "Human Response Patterns" developed by NANDA, historical foundations of the
      concept of relating, the use of this construct by nursing and other disciplines.
      CONCLUSIONS: Concept analysis of relating resulted in conceptual and operational
      definitions. The efficacy of further developing nursing's taxonomic tree on the
      nine human response patterns has been advanced.

PMID- 9624988
TI  - Application of the Neuman Systems Model to teaching health assessment and nursing
      process.
AB  - TOPIC: A nursing theory framework for teaching health assessment. PURPOSE: To
      improve teaching of health assessment and nursing process to beginning-level
      baccalaureate nursing students. SOURCES: The Assessment and Analysis Guideline
      Tool, published and unpublished literature, personal observation, and faculty
      feedback were used in tool development. CONCLUSIONS: Faculty concluded that
      students who could envision the connection of the Neuman Systems Model and NANDA
      nursing diagnoses through the nursing process would be better able to understand
      the nursing model and choose appropriate nursing diagnoses for client care.

PMID- 9624989
TI  - Is nursing in name only?

PMID- 9624990
TI  - Case study: parenting of a child with spina bifida.

PMID- 9624991
TI  - Mapping nursing intervention data into the Nursing Interventions Classification
      (NIC): process and rules.
AB  - TOPIC: Uniform language in nursing is needed to clearly depict the contributions
      of nursing in the healthcare arena but little data related to nursing
      interventions and patient outcomes are standardized. PURPOSE: To investigate the
      feasibility of mapping nonstandardized nursing interventions into standardized
      language using the Nursing Interventions Classification (NIC). SOURCE: Data from
      a Midwest community hospital's computerized information system. CONCLUSIONS:
      Results demonstrate that nonstandardized nursing orders can be mapped into
      standardized language using the NIC.

PMID- 9624992
TI  - Mapping nursing interventions from a hospital information system to the Nursing
      Interventions Classification (NIC).
AB  - TOPIC: Using the Nursing Interventions Classifications (NIC) as a standard to
      classify interventions identified in a hospital intervention system. SOURCES:
      Literature and the authors experience with standardized data systems for nursing.
      PURPOSE: To describe the processes used and the issues that arose as
      interventions from a hospital nursing information system were mapped to
      interventions in the NIC. CONCLUSIONS: The NIC provided a standard for the
      classification of nursing interventions from a hospital information system
      resulting in data that could be compared across sites. Ongoing testing of nursing
      intervention classifications is recommended.

PMID- 9624993
TI  - Synthesis of methods, rules, and issues of standardizing nursing intervention
      language mapping.
AB  - TOPIC: Nursing language mapping. PURPOSE: To synthesize the methods, rules and
      issues described in two studies that mapped nonstandardized nursing
      orders/interventions into the Nursing Interventions Classification (NIC).
      SOURCES: The methods and results of studies conducted by Moorhead & Delaney and
      Coenen et al. CONCLUSIONS: Results indicate that the NIC is an effective
      classification of mapping nursing orders/interventions to support across-site
      comparisons of nursing treatments. A set of decision rules to support mapping of
      interventions to the NIC is outlined.

PMID- 9624995
TI  - A working paper looking at nursing, research and the higher education context.

PMID- 9624994
TI  - Accuracy of nurses' diagnoses of psychosocial responses.
AB  - PURPOSE: To describe the accuracy of staff nurses' diagnoses or interpretations
      of the human responses of patients in hospital settings. METHODS: The sample was
      62 staff nurses in three hospitals who assessed and diagnosed the psychosocial
      problems of one to four patients. Two trained raters followed with assessment,
      diagnosis, and ratings of nurses' accuracy of 153 cases. A seven-point interval
      scale was used to judge accuracy. FINDINGS: The means of accuracy scores across
      nurses were significantly different (f = 1.66; p < .05; df = 2.59). A significant
      percentage of nurses' diagnoses were scored at the two highest levels of accuracy
      (45.2%), and 12.8% were scored at the three lowest levels of accuracy. According
      to the expert raters, a high percentage of patients (54.4%) were experiencing
      fear or anxiety. CONCLUSIONS: More attention needs to be given to the accuracy of
      nurses' diagnoses of psychosocial responses.

PMID- 9624996
TI  - Governing the future.

PMID- 9624997
TI  - Degrees of separation.

PMID- 9624998
TI  - This way up.

PMID- 9624999
TI  - Partners at last.

PMID- 9625000
TI  - Probation makes perfect?

PMID- 9625001
TI  - Capital support.

PMID- 9625002
TI  - Coping by cutting.

PMID- 9625003
TI  - Observing nurse-patient interaction.
AB  - This article describes an observational study of nurses' interactions with
      mentally ill young people in a regional adolescent unit. Nurses initiated more
      than twice as many interactions as patients and were consistent in the average
      length of time they interacted with the young people. The author recommends that
      future studies include more qualitative data on the nature of interactions.

PMID- 9625004
TI  - Clinical supervision for nurse lecturers.
AB  - This article builds on a previous one which discussed the use of de Bono's
      thinking tool, 'six thinking hats' in the clinical, managerial, educational and
      research areas of nursing (Lewis 1995). This article explores clinical
      supervision and describes how the six thinking hats may be used as a reflective
      tool in the supervision of nurse lecturers who teach counselling skills.

PMID- 9625005
TI  - Psychiatric intensive care: a developing specialty.
AB  - Care of acutely ill psychiatric patients is a problematic area for the NHS. This
      article charts the development of the specialty of psychiatric intensive care and
      discusses the major issues for staff and patients.

PMID- 9625006
TI  - Management of acute asthma in children.

PMID- 9625007
TI  - Liver transplantation and bile analysis: a parallel evolution.

PMID- 9625009
TI  - Cytomegalovirus infection enhances the neointima formation in rat aortic
      allografts: effect of major histocompatibility complex class I and class II
      antigen differences.
AB  - BACKGROUND: The development of chronic rejection has emerged as a major cause of
      long-term graft failure. Previous studies have demonstrated that cytomegalovirus
      (CMV) infection is associated with an increased incidence of chronic allograft
      rejection in renal, cardiac, and aortic allografts. This study was designed to
      investigate the effects of the major histocompatibility complex (MHC) class I or
      class II mismatches on CMV-enhanced chronic rejection. METHODS: Aortic
      transplantation was performed between different inbred rat strain combinations;
      the Lewis to RP combination was class I-mismatched and Wag/Rij to RP class II
      mismatched. At 7, 28, and 90 days after transplantation, the intensity of chronic
      rejection in mismatched grafts with or without CMV infection was evaluated using
      histological and immunohistological analysis. RESULTS: The results of this study
      demonstrated that CMV infection led to an increased influx of monocytes/
      macrophages in class I-mismatched grafts at 1 week after transplantation and
      enhanced infiltration of T lymphocytes in class II-mismatched grafts at 4 weeks.
      Although more vascular lesions were observed in the class II-mismatched
      combinations, an intensified neointima formation by CMV infection was observed
      only in the MHC class I-mismatched allografts. CONCLUSIONS: CMV infection may
      increase neointima formation of allografts when an MHC class I disparity between
      donor and recipient is present. This may be associated with the increased
      perivascular influx of monocytes/macrophages observed in CMV-infected animals
      early after transplantation.

PMID- 9625008
TI  - Selective targeting of Kupffer cells with liposomal butyrate augments portal
      venous transfusion-induced immunosuppression.
AB  - BACKGROUND: Enhanced Kupffer cell production of the immunosuppressive arachidonic
      acid metabolite prostaglandin E2 (PGE2) has been shown to be a mechanism of the
      immunosuppressive effect of portal venous transfusions (PVT). Butyrate, a four
      carbon short-chain fatty acid, has received increased attention because of its
      ability to enhance gene transcription. This study tested the hypothesis that the
      intrahepatic delivery of butyrate enhances Kupffer cell PGE2 production and thus
      augments the immunosuppressive effect of PVT. METHODS: Butyrate was incorporated
      into liposomes and administered intravenously to Lewis rats. Control rats were
      administered liposomes without butyrate. Twenty-four hours after liposome
      injection, rats were administered a PVT of 1 ml of Wistar-Furth blood. Kupffer
      cells were isolated, and PGE2 and tumor necrosis factor-alpha levels were
      measured in the culture medium after 24 hr. Additionally, Kupffer cells from
      butyrate-treated and control animals were added to one-way mixed lymphocyte
      reaction cultures. RESULTS: Intrahepatic delivery of butyrate via liposomes
      increased Kupffer cell PGE2 (3800+/-1220 vs. 1010+/-119 pg/ml, P<0.05) and
      decreased tumor necrosis factor-alpha (1670+/-81 vs. 3360+/-415 pg/ml, P<0.01)
      production as compared with controls. Butyrate also augmented the Kupffer cell
      mediated immunosuppression as demonstrated by significant depression of the mixed
      lymphocyte reaction (690+/-119 vs. 3850+/-148 cpm, P<0.01). CONCLUSION: The
      results support the hypothesis that intrahepatic delivery of butyrate enhances
      Kupffer cell PGE2 production, and specific targeting of Kupffer cells with
      liposomes containing immunomodulating agents such as butyrate may be a useful
      means of augmenting immunosuppression protocols in organ transplantation.

PMID- 9625010
TI  - Dietary omega-3 and omega-9 fatty acids uniquely enhance allograft survival in
      cyclosporine-treated and donor-specific transfusion-treated rats.
AB  - BACKGROUND: Both laboratory and clinical studies have shown that dietary lipids
      may affect immunologic responses. This study was conducted to compare different
      classes of long-chain unsaturated fatty acids for their effect on allograft
      survival in animals receiving a donor-specific transfusion and a short course of
      low-dose cyclosporine (CsA). METHODS: Heterotopic ACI strain cardiac allografts
      were transplanted to Lewis strain rat recipients given diets with different lipid
      composition. In experiment 1, animals received CsA for 14 days and different
      diets were enriched with lipids with high concentrations of omega-3, omega-6, or
      omega-9 fatty acids. In experiment 2, animals received CsA for only 8 days and
      different diets were enriched with corn oil (omega-6), canola oil (omega-3 and
      omega-9), fish oil (omega-3) or a mixture of sunflower oil and fish oil (omega-3
      and omega-9). RESULTS: In experiment 1, animals receiving the diet with 30%
      sunflower oil had the best allograft survival (200+/-42 days vs. 53+/-8 days for
      regular chow plus donor-specific transfusion and CsA, P<0.05). In experiment 2,
      diets containing canola oil (a mixture of omega-3 and omega-9 fatty acids) were
      associated with the best survival (P=0.0011 vs. regular chow). CONCLUSION:
      Dietary omega-3 and omega-9 fatty acids both enhanced cardiac allograft survival
      in a stringent rat strain combination. Canola oil is a convenient oil for
      administering both alpha-linoleic acid (omega-3) and oleic acid (omega-9) in a
      palatable form for human consumption. Further investigation of the potential
      usefulness of lipids in transplant therapy is warranted.

PMID- 9625011
TI  - Immunosuppression preventing concordant xenogeneic islet graft rejection is not
      sufficient to prevent recurrence of autoimmune diabetes in nonobese diabetic
      mice.
AB  - BACKGROUND: We and others have reported previously that the immunosuppressant,
      leflunomide (Lef), can prevent allogeneic and xenogeneic islet graft rejection in
      streptozocin (STZ)-induced diabetic animals. However, whether Lef required to
      prevent islet graft rejection is sufficient to prevent the recurrence of
      autoimmune diabetes has not been addressed. METHODS: The effect of Lef on
      concordant xenogeneic islet graft in STZ-induced diabetic mice and autoimmune
      nonobese diabetic (NOD) mice were studied. Then, whether Lef prevents the onset
      of spontaneous diabetes in young NOD mice and the recurrence of diabetes after
      major histocompatibility complex (MHC)-matched islet transplantation in diabetic
      NOD mice were investigated. RESULTS: In STZ-induced diabetic BALB/c mice, Lef
      treatment significantly prolonged rat islet graft survival. However, Lef could
      not significantly prolong rat islet graft survival in autoimmune diabetic NOD
      mice. For prevention studies, treatment with Lef at 30 mg/ kg/day from 4 weeks to
      20 weeks of age significantly reduced the incidence of spontaneous diabetes in
      NOD mice. However, when the NOD mice were treated from 8 to 24 weeks of age, the
      incidence of spontaneous diabetes was not significantly reduced as compared to
      the incidence of diabetes in the untreated female NOD mice at 28 weeks of age.
      Finally, in the MHC-matched islet transplant model, Lef could not significantly
      prolong MHC-matched nonobese diabetes-resistant mice islet graft survival in NOD
      mice. CONCLUSIONS: Lef preventing concordant xenogeneic islet graft rejection is
      not sufficient to prevent the recurrence of autoimmune diabetes in NOD mice. We
      believe that controlling autoimmunity after islet transplantation will lead the
      way to promote successful clinical islet transplantation in the future.

PMID- 9625012
TI  - Protective effect of N-acetyl-L-cysteine on the renal failure induced by inferior
      vena cava occlusion.
AB  - BACKGROUND: Renal ischemia is produced during orthotopic liver transplantation
      when the inferior vena cava is clamped above the renal veins (inferior vena cava
      occlusion [IVCO]), and it often leads to postoperative renal failure. Although
      free radicals and nitric oxide (NO) have been implicated in the pathogenesis of
      ischemic renal failure, the effect of free radical scavengers in this model is
      unknown. METHODS: The effects of N-acetyl-L-cysteine (NAC), a free radical
      scavenger, on the acute renal failure that follows IVCO were evaluated in
      pentobarbital-anesthetized dogs. The effect of NO synthesis inhibition with NG
      nitro-L-arginine methyl ester (NAME) was also studied. Renal vascular endothelial
      function was tested by infusing acetylcholine (Ach) into the renal artery before
      the ischemia and during reperfusion. RESULTS: Renal failure developed during IVCO
      and persisted during reperfusion in all groups. However, in NAC-pretreated dogs,
      the glomerular filtration rate recovered progressively, reaching 31% of basal
      preischemic values 150 min after reperfusion. During reperfusion, fractional
      excretion of sodium increased above preischemic values only in the control group,
      which indicates a beneficial effect of NAC and NAME on the tubular dysfunction
      observed during reperfusion. The renal response to Ach was abolished in control
      dogs and in animals given NAME during reperfusion, which indicates endothelial
      dysfunction. However, in NAC-pretreated dogs, the renal response to Ach was
      preserved during reperfusion. CONCLUSIONS: These results demonstrate that NAC
      ameliorates the renal failure and renal endothelial dysfunction induced by IVCO.
      This protective effect was abolished by NAME, which suggests that NO is involved
      in the beneficial effects of NAC. These data also suggest that the use of NAC
      could be beneficial in ameliorating the acute renal failure observed after
      orthotopic liver transplantation.

PMID- 9625013
TI  - Oxidative stress and lipid abnormalities in renal transplant recipients with or
      without chronic rejection.
AB  - BACKGROUND: The histological picture of chronic rejection with endothelial
      lesions and vascular hyperplasia resembles the early arteriosclerotic lesions. As
      increasing evidence suggests a role for oxidative stress in arteriosclerosis, we
      examined whether chronic rejection in renal transplant recipients was associated
      with increased oxidative stress markers. METHODS: We investigated lipid
      metabolism and oxidative stress in 77 renal transplant recipients. Group I
      patients (n=34; 48+/-2 years old, 12 women, 22 men) had no clinical or
      histological signs of chronic rejection, whereas group II patients (n=43; 47+/-3
      years old, 15 women, 28 men) had histologically proven chronic rejection. All
      patients were treated with cyclosporine and steroids. Lipid metabolism was
      evaluated by determining total cholesterol, triglycerides, high-density
      lipoprotein cholesterol, apolipoproteins AI and B, and lipoprotein (a). Oxidative
      stress was evaluated by determining: (i) the end product of lipid peroxidation,
      malonyldialdehyde (MDA), and erythrocyte polyunsaturated fatty acids; (ii) the
      nonenzymatic antioxidant system: erythrocyte alpha-tocopherol and glutathione;
      and (iii) the enzymatic antioxidant system: erythrocyte superoxide dismutase and
      plasma glutathione peroxidase. Results were compared with those of a control
      group (38 healthy volunteers). RESULTS: Compared with controls, renal transplant
      recipients had significantly increased total cholesterol, triglyceride, and
      apolipoprotein B levels; they also had, in association with these lipid
      abnormalities, a significant increase in MDA and a significant decrease in
      erythrocyte polyunsaturated fatty acids, as well as a significant decrease in
      enzymatic and nonenzymatic antioxidant defense mechanisms. In contrast to lipid
      disturbances, where no difference was observed between groups I and II, markers
      of oxidative stress were significantly higher in group II compared with group I
      (MDA: 1.87+/-0.43 and 1.62+/-0.31 nmol/ml, respectively, P<0.05). The red blood
      cell antioxidative defense mechanisms were significantly decreased in group II
      compared with controls (erythrocyte alpha-tocopherol: 0.61+/-0.38 and 1.08+/-0.31
      mg/L, respectively, P<0.01; superoxide dismutase: 1.08+/-0.2 and 1.32+/-0.31 U/mg
      Hb, respectively, P<0.01). CONCLUSION: Our data show that oxidative stress with a
      decrease in antioxidant defenses is associated with kidney transplantation. In
      addition, oxidative stress markers are particularly increased in transplant
      recipients with chronic rejection, which suggests that oxidative stress may
      participate in the development and/or progression of vascular lesions observed in
      these patients.

PMID- 9625014
TI  - Histological features predictive of recurrence of primary biliary cirrhosis after
      liver transplantation.
AB  - BACKGROUND: Recurrence of primary biliary cirrhosis (PBC) within liver allografts
      remains a controversial issue. The aims of this study were to evaluate this risk
      and to determine the presence, if any, of a predictive histological feature.
      METHODS: We reviewed the most recent and the 1-year protocol liver biopsies of 69
      patients who received transplants for PBC and of 53 control patients.
      Histological features consistent with PBC recurrence included nonsuppurative
      destructive cholangitis, mixed portal infiltrate, fibrosis, and ductopenia. A
      complete evaluation was undertaken in each patient with these histological
      features. RESULTS: These histological features were present in six patients who
      received transplants for PBC (8.7% vs. 0% in the control group) and occurred
      between 1 and 8 years after transplant. In five of the six patients, anti
      mitochondrial antibody-2 (anti-M2) antibodies remained at high titers.
      Cholestasis was present in four patients, and clinical symptoms in two patients.
      All six patients were negative for hepatitis C antibodies and hepatitis C RNA in
      their serum. None had bile duct obstruction. The presence of plasma cells in the
      portal infiltrate at 1 year after transplant was predictive of this risk of
      recurrence. CONCLUSION: The risk of PBC recurrence is real (8.7%). The presence
      of plasma cells in the portal infiltrate seems to be an early marker of
      recurrence of PBC in patients transplanted for this indication.

PMID- 9625015
TI  - Monitoring eosinophil activation and liver function after liver transplantation.
AB  - BACKGROUND: Portal tract eosinophil infiltration and an increase in the blood
      eosinophil count (EOS) have been shown to be specific markers of liver allograft
      rejection. The graft eosinophil infiltration is associated with the local release
      of eosinophil cationic protein. Therefore, serum eosinophil cationic protein
      concentration (ECP) is a potential marker for acute allograft rejection. We
      investigated the chronological relationship among and diagnostic value of serial
      changes in EOS, ECP, and liver function tests (LFTs) following liver
      transplantation. METHODS: EOS, ECP, serum alpha-glutathione S-transferase
      concentration, and conventional LFTs were measured in serial samples collected
      over the first 3 postoperative months following 58 liver transplants. The
      diagnostic potential of each test, alone or in combination, was reviewed over the
      entire follow-up period. RESULTS: EOS and ECP increased at a median period of 3.5
      and 4 days, respectively, before the diagnosis of acute rejection, and this
      increase was significantly earlier than the corresponding changes in LFTs
      (P<0.05). There was a significant correlation between the day of the first
      increase in EOS and alpha-glutathione S-transferase (rs=0.535; P=0.009) and EOS
      and alanine transaminase (rs=0.629; P=0.004). The optimum combination of tests
      for the diagnosis of acute rejection was an increase in both EOS and GST with a
      predictive efficiency of 84%. CONCLUSIONS: Increases in EOS and ECP are early
      indicators of acute liver allograft rejection and precede evidence of
      hepatocellular damage. However, an increase in ECP was also frequently associated
      with infection. Therefore, we recommend the regular monitoring of EOS in
      conjunction with routine LFTs after liver transplantation as an aid to the early
      diagnosis of acute rejection.

PMID- 9625016
TI  - Subdural hygromas after bone marrow transplantation: results of a prospective
      study.
AB  - BACKGROUND: Subdural hygromas after bone marrow transplantation (BMT) have been
      occasionally found in patients with persisting headache and vomiting. We assessed
      the incidence of subdural hygromas after BMT and tried to define possible risk
      factors associated with this complication. METHODS: Fifty bone marrow graft
      recipients surviving more than 30 days were consecutively enrolled into a
      prospective study. Cranial CT scans were performed before and 30 days after BMT.
      Clinical data and symptoms were recorded daily during the first 30 days after
      BMT. In patients with subdural hygromas, a magnetic resonance imaging scan and
      monthly follow-up cranial computed tomography scans were performed until fluid
      collections had resolved completely. RESULTS: In 9 of the 50 patients (18%) who
      survived 30 days after transplantation, newly acquired subdural hygromas were
      found. Patients with hygromas suffered significantly longer and more severely
      from headache and vomiting (P=0.01). Application of intrathecal methotrexate and
      arterial hypertension occurred significantly more often in patients with hygromas
      (P=0.01). In a stepwise logistic regression model, arterial hypertension and
      intrathecal methotrexate application were the only independent risk factors for
      the development of hygromas. Monthly follow-up cranial computed tomography scans
      showed that all hygromas resolved completely after a median of 60 days after
      diagnosis (range: 30-120 days). CONCLUSIONS: Subdural hygromas are a frequent
      complication after BMT within the first 30 days after transplantation. They are
      reversible and disappear within 2-3 months. The need for routine application of
      intrathecal methotrexate in standard risk leukemia patients should be critically
      addressed. Furthermore, close monitoring of blood pressure and immediate
      antihypertensive therapy might contribute to avoid formation of subdural
      hygromas.

PMID- 9625017
TI  - Anti-skeletal muscle glycolipid antibodies in human heart transplantation as
      predictors of acute rejection: comparison with other risk factors.
AB  - In forty-five patients who underwent orthotopic heart transplantation, the titer
      of anti-human skeletal muscle glycolipid antibodies (AGA) present in the sera at
      the moment of transplantation was correlated with the number of histologically
      diagnosed cellular grade 3A and humoral acute rejection episodes during the first
      120 days after transplantation. Determination of a cutoff value of 0.800 for the
      AGA level was determined by a receiver operating characteristic curve. Thirteen
      of 19 patients (68.4%) with an AGA titer above 0.800 developed 24 severe
      rejection episodes, and of the 26 patients with an AGA titer below 0.800, only 4
      (15.3%) presented 6 severe rejection episodes during that time. This was
      especially evident for the humoral rejection episodes, which were diagnosed in
      only 1 of the 26 patients with AGA below 0.800 and in 7 of the 19 with AGA above
      0.800. Comparison by univariate analysis of other well-known risk factors for a
      greater number of rejection episodes during the early posttransplant period with
      the AGA level at the moment of transplantation revealed that the latter
      distinguished a greater number of patients at risk than the other factors, such
      as a female donor, the lymphocyte direct cross-match, or the status of the
      patients at transplantation; the odds ratios were 6.33 for the AGA level, 3.17
      for the direct cross-match, and 2.76 for the status at transplantation. By
      multiple logistic regression analysis, the only relevant risk factors in our
      group of patients were the AGA level (P=0.0009) and the status at transplantation
      (P=0.0285). These results indicate that determination of the AGA level at the
      moment of transplantation could represent a useful method for distinguishing
      which patients are at risk for a greater number of rejection episodes during the
      early posttransplant period, with a greater sensitivity than other risk factors.

PMID- 9625018
TI  - Cardiac allograft tolerance: failure to develop in interleukin-4-deficient mice
      correlates with unusual allosensitization patterns.
AB  - BACKGROUND: The development of long-term allograft survival and understanding the
      mechanism(s) by which it is induced are major goals of experimental
      transplantation. Studies by several different investigators have provided
      conflicting evidence for the role of interleukin (IL)-4 in the process of
      allograft rejection or long-term allograft survival. These studies examine the
      role of IL-4 in experimental cardiac allograft rejection and in inducing long
      term allograft survival. A possible mechanism for long-term allograft maintenance
      via alternative allosensitization is discussed. METHODS: Adult IL-4-intact or IL
      4-deficient (knockout, KO) C57BL/6 (B6) mice were transplanted with heterotopic
      DBA/2 cardiac allografts and immunosuppressed either with gallium nitrate (GN),
      or the anti-CD4 monoclonal antibody, GK1.5. Cellular allosensitization was
      assessed by testing the allograft recipients for donor-reactive delayed-type
      hypersensitivity (DTH) responses. The presence of antigen-driven suppressive
      mechanisms was assessed using a linked unresponsiveness (bystander suppression)
      DTH assay. RESULTS: In general, the results were the same with either GN or
      GK1.5. We observed that (1) IL-4 is not required for acute allograft rejection or
      allogeneic DTH responses in nonsuppressed mice, (2) IL-4 is required for long
      term allograft survival in immunosuppressed mice, (3) immunosuppression creates a
      requirement for IL-4 in major histocompatibility complex self-restricted, but not
      allorestricted, DTH responses, and (4) the development of alloantigen-dependent
      linked DTH unresponsiveness (bystander suppression) in allograft recipients
      requires IL-4. CONCLUSION: In summary, these studies demonstrate a common
      requirement for IL-4 during the development of long-term allograft survival and
      the concurrent development of alloantigen-dependent DTH down-regulation in
      cardiac allograft recipients after immunosuppression.

PMID- 9625019
TI  - Identification of an indirectly presented epitope in a mouse model of skin
      allograft rejection.
AB  - BACKGROUND: The indirect pathway of allorecognition involves the processing and
      presentation of donor molecules by recipient antigen-presenting cells to
      alloreactive CD4+ T cells. Our objective was to assess the occurrence and
      significance of the indirect presentation of allogeneic major histocompatibility
      complex molecules in the rejection of major histocompatibility complex class I
      disparate skin. METHODS: A mouse model of allograft rejection was developed in
      which tail skin from C57.BL/10 (H2b) donors was transplanted onto B10.A(5R)
      recipients resulting in an allogeneic mismatch at the D locus. T-cell depletion
      studies were used to characterize T-cell subset involvement in rejection.
      B10.A(5R) mice were immunized with pools of overlapping peptides spanning the
      polymorphic region of Db in order to identify Db-derived epitopes involved in
      rejection. The relevance of these epitopes was assessed through immunization of
      recipient mice with peptides before skin grafting to observe the effect of
      presensitization on the kinetics of rejection. RESULTS: Rejection of Db-disparate
      skin by B10.A(5R) was delayed by CD4 and CD8+ T-cell depletion, indicating the
      significance of both cell types in rejection. At least six immunogenic peptides
      were identified, all of which contained a cryptic T-cell epitope. One peptide,
      however, was able to accelerate the rejection of Db-disparate skin.
      Presensitization of B10.A(5R) mice with this peptide also resulted in an increase
      in alloantibody, indicating the presence of a physiological as well as a cryptic
      epitope. Presensitization of mice with a peptide containing a distinct cryptic
      epitope, however, failed to influence rejection. CONCLUSIONS: These findings
      demonstrate a significant role for the indirect pathway of antigen presentation
      in allograft rejection.

PMID- 9625020
TI  - In vivo alloreactive potential of ex vivo-expanded primary T lymphocytes.
AB  - BACKGROUND: We are presently investigating the therapeutic potential of herpes
      simplex-thymidine kinase-expressing donor T cells in the setting of a T cell
      depleted allogeneic bone marrow transplantation. The generation, expansion, and
      selection of the gene-modified T cells require a 12-day ex vivo culture period in
      high-dose interleukin (IL)-2 that could significantly alter their in vivo
      alloreactivity. METHODS: We evaluated the alloreactive potential of such cultured
      cells in a murine allogeneic bone marrow transplantation model. RESULTS: The
      present studies demonstrate that ex vivo-expanded cultured T cells are capable of
      strong alloreactivity as evidenced by the occurrence of lethal acute graft-versus
      host disease (GVHD). However, GVHD mortality after administration of the cultured
      T cells occurred later than after the administration of a same number of fresh T
      cells. Similar kinetics of GVHD-induced mortality between cultured and fresh T
      cells required a 10-fold increase in the number of cultured T cells, indicating a
      reduced alloreactive potential of these cells. The addition of a 2-day "resting"
      period in low-dose IL-2 resulted in T cells with enhanced alloreactive potential
      identical to the alloreactivity observed with fresh T cells. CONCLUSION: Ex vivo
      IL-2-expanded T cells are capable of significant in vivo alloreactivity. However,
      an increase in the number of cultured T cells administered or the introduction of
      a short resting culture period prior to infusion is necessary in order to achieve
      in vivo alloreactivity identical to the alloreactivity observed with fresh T
      cells.

PMID- 9625022
TI  - Human cytomegalovirus (HCMV) leukodnaemia correlates more closely with clinical
      symptoms than antigenemia and viremia in heart and heart-lung transplant
      recipients with primary HCMV infection.
AB  - BACKGROUND: In the last few years, human cytomegalovirus (HCMV) viremia, pp65
      antigenemia, and leuko- and plasma-DNAemia have been developed to quantitate
      virus in blood of immunocompromised patients with HCMV infection. However, thus
      far, no conclusive studies have been performed to define the correlation of each
      of the different assays with clinical symptoms in primary HCMV infections.
      METHODS: This correlation was investigated in a population of 20 heart and heart
      lung transplant recipients with primary HCMV infection using standardized
      virological methods. RESULTS: Median peak HCMV viremia, antigenemia, and
      leukoDNAemia levels were 110 (0-2,000) p72-positive fibroblasts, 450 (27-2,000)
      pp65-positive leukocytes, and >10,000 (1,358-10,000) genome equivalents (GE) in
      the 14 symptomatic patients and 18 (1-130) p72-positive fibroblasts, 86.5 (5-350)
      pp65-positive leukocytes, and 248 (10-863) GE in the six asymptomatic patients,
      respectively. The difference was statistically significant for antigenemia
      (P=0.009) and leukoDNAemia (P<0.0001). However, on an individual basis, unlike
      viremia and antigenemia, all DNA peaks of the 6 asymptomatic patients were below
      the DNA range of the 14 symptomatic patients (<1,000 GE), while all the 14
      symptomatic patients had DNA peaks higher than those of asymptomatic patients
      (>1,000 GE). Follow-up confirmed these results, showing that 1,000-2,000 GE was
      the threshold zone for emergence of clinical symptoms. Symptoms were never
      observed in patients with secondary DNA peaks, except for one patient suffering
      from an HCMV organ localization (HCMV gastritis). CONCLUSIONS: LeukoDNAemia is
      the viral parameter of choice for monitoring of primary HCMV infections and
      antiviral treatment in heart and heart-lung transplant recipients. In this
      patient population, antigenemia-guided preemptive therapy could be replaced by
      leukoDNAemia-based antiviral therapy.

PMID- 9625021
TI  - Kinetics of intragraft cytokine expression, cellular infiltration, and cell death
      in rejection of renal allografts compared with acceptance of liver allografts in
      a rat model: early activation and apoptosis is associated with liver graft
      acceptance.
AB  - BACKGROUND: Liver transplants in the rat strain combination PVG-to-Dark Agouti
      are spontaneously tolerated, whereas kidney transplants in the same strain
      combination are rejected in 7-9 days. METHODS: To identify organ-specific
      differences that might yield further information about the mechanism of tolerance
      induction in this strain combination, liver or kidney grafts, spleen, and
      draining lymph nodes were harvested at days 1, 3, 5, and 7, and examined by
      immunohistochemistry, terminal deoxynucleotide transferase-mediated dUTP nick end
      labeling assay, and reverse transcriptase-polymerase chain reaction for
      interferon-gamma, interleukin (IL)-2, IL-4, and IL-10. RESULTS: Renal allograft
      rejection was associated with the progressive development of an intense
      mononuclear cell infiltrate. Markers of lymphocyte activation and cytokine up
      regulation appeared from day 3, and many apoptotic parenchymal cells were noted
      on days 5-7, at the peak of rejection. Conversely, liver allograft tolerance was
      associated with more rapid infiltration by activated T cells and earlier
      increases in cytokine expression, but with a more limited degree of cellular
      infiltration. Concurrent with the early activation, high levels of apoptosis were
      found in areas of leukocyte infiltrate, paralleling the disappearance of
      activated T cells from the graft between days 3 and 5. CONCLUSIONS: Apoptosis of
      infiltrating leukocytes in liver allografts may represent an important process in
      the induction of spontaneous liver transplant tolerance and may underlie the
      abortive nature of the effector response observed within tolerated livers. In
      contrast, activated cells in renal allografts in the same strain combination
      survive and proliferate, express high levels of cytokines, and are efficient in
      bringing about graft destruction.

PMID- 9625023
TI  - Tolerance induction by "megadose" hematopoietic transplants: donor-type human
      CD34 stem cells induce potent specific reduction of host anti-donor cytotoxic T
      lymphocyte precursors in mixed lymphocyte culture.
AB  - BACKGROUND: Recently, the use of megadoses of CD34+ hematopoietic progenitors has
      been reported to abrogate resistance to engraftment, thus overcoming major
      histocompatibility barriers in bone marrow transplantation in leukemia patients.
      METHODS: The ability of human CD34+ cells to possess potent tolerizing activity
      was studied by limiting dilution analysis of cytotoxic T lymphocyte (CTL)
      precursors (CTL-p) in human peripheral blood lymphocytes after addition of
      purified CD34+ cells. RESULTS: The addition of purified human CD34+ cells to
      primary mixed lymphocyte culture led to a marked reduction of antiallogeneic CTL
      p frequency against stimulator cells of the same origin, compared with the
      response against cells of third-party origin. The CD34+ cells caused a marked
      inhibition of the CTL activity, when added at an equal number with the responder
      T cells, and they were still present after the mixed lymphocyte culture, which
      suggests that no significant killing of CD34+ cells had occurred. The tolerizing
      activity is abrogated by irradiation and requires cell contact. This pattern of
      tolerization most closely resembles what has been ascribed to veto cells in other
      systems. Phenotypic analysis of the purified CD34+ cells showed that they express
      MHC class I and class II antigens, but do not express costimulatory molecules of
      the B7 family. CONCLUSIONS: It is possible, that CD34+ cells in the megadose
      transplants-perhaps by their inability to provide costimulatory molecules-are
      actively reducing the frequency of CTL-p directed against their antigens, and
      thereby help to overcome allogeneic rejection, and enhance their own engraftment.

PMID- 9625024
TI  - Reversible symmetric polyneuropathy with paraplegia after heart transplantation.
AB  - BACKGROUND: Neurotoxicity is a well-recognized side effect of cyclosporine
      therapy in transplant recipients. Cyclosporine can cause a wide range of adverse
      effects on both the central and peripheral nervous systems. METHODS: We present a
      case history of symmetric polyneuropathy with flaccid paraplegia, a rare
      neurological complication of cyclosporine administration. RESULTS: Blood levels
      of the drug above the therapeutic range accompanied the neurological
      manifestations. The syndrome subsided fully with dose reduction. Patients'
      symptoms were attributed to axonal degeneration of the peripheral nerves,
      according to electromyography findings. CONCLUSIONS: Cyclosporine neurotoxicity
      should always be considered in patients with neurological complications following
      transplantation. The case presented in this article illustrates an additional
      potential mechanism of this adverse effect, namely, axonal degeneration of the
      peripheral nerves, causing symmetric polyneuropathy.

PMID- 9625025
TI  - Merkel cell carcinoma in a renal transplant patient: increased incidence?
AB  - The identification of malignancies associated with transplantation has led to
      enhanced vigilance and care in these patients, as well as insight into the
      pathogenesis of select malignancies. We report a case of Merkel cell carcinoma,
      an uncommon cutaneous malignancy of neuroendocrine origin, diagnosed in a 65-year
      old Caucasian man 6 years after renal transplantation. While it is well known
      that transplant patients are at increased risk for squamous cell carcinomas of
      the skin, other types may also have an increased frequency. We suggest that
      Merkel cell carcinoma could have an increased incidence in the transplant
      population.

PMID- 9625026
TI  - Interaction between tacrolimus and chloramphenicol in a renal transplant
      recipient.
AB  - BACKGROUND: The metabolism of tacrolimus is influenced by several medications
      when they are given concurrently. We report the interaction between tacrolimus
      and chloramphenicol in a renal transplant recipient. METHODS: An adolescent with
      vancomycin-resistant Enterococcus was given standard doses of chloramphenicol.
      Tacrolimus trough levels increased, and the dose was adjusted to maintain the
      target trough level. Pharmacokinetic studies were obtained during chloramphenicol
      administration and 14 days after its discontinuation. RESULTS: Toxic levels of
      tacrolimus were seen on the second day of chloramphenicol administration,
      requiring an 83% reduction in the tacrolimus dose. The dose-adjusted area under
      the curve value for tacrolimus was 7.5-fold greater while the patient was on
      chloramphenicol. These data are consistent with inhibition of tacrolimus
      clearance by chloramphenicol CONCLUSIONS: Chloramphenicol interferes with
      tacrolimus metabolism. Careful monitoring of tacrolimus trough levels during
      concomitant chloramphenicol therapy is recommended to avoid toxicity.

PMID- 9625027
TI  - Potential interaction of troglitazone and cyclosporine.
AB  - BACKGROUND: Troglitazone (Rezulin) is a promising new oral hypoglycemic agent
      recently approved by the Federal Drug Administration for use in type II diabetes
      mellitus. Although troglitazone is not metabolized by the cytochrome p450 3A
      isozyme family, it is a potential inducer of this system. Other medications,
      e.g., rifampin and phenobarbital, which also induce p450 3A activity, have been
      reported to significantly decrease cyclosporine (CsA) concentrations. METHODS: We
      report a case of a stable renal transplant patient who had a decrease in CsA
      concentration after beginning troglitazone and who subsequently developed an
      acute rejection episode. We then reviewed all stable renal patients begun on
      troglitazone over the previous 6 months. RESULTS: The seven transplant patients
      who had been started on troglitazone therapy experienced a statistically and
      clinically significant decrease in CsA 12-hr trough levels immediately after the
      institution of troglitazone therapy. CONCLUSION: A potential interaction exists
      between troglitazone and CsA. Transplant patients on CsA who receive troglitazone
      therapy should be monitored closely.

PMID- 9625028
TI  - Visceral leishmaniasis (Kala-Azar) in transplant recipients: case report and
      review.
AB  - BACKGROUND: In endemic areas, visceral leishmaniasis has been identified as an
      opportunistic infection in patients with derangements in their cellular immune
      system. METHODS: We report a renal transplant patient with visceral
      leishmaniasis. We also reviewed the previously published cases of 17 organ
      transplant recipients with this parasitic disease. RESULTS: Visceral
      leishmaniasis occurred a median time of 8 months after transplantation, and the
      clinical picture was characterized by fever, splenomegaly, and blood cytopenias.
      Leishmaniae were detected in bone marrow in 16 of 18 patients and diagnostic
      serology results were found in 8 of 10 tested patients. Pentavalent antimonials
      were used to treat 16 patients, five of which developed pancreatitis. Five of 18
      patients died, including two untreated patients. Relapses of visceral
      leishmaniasis occurred in 4 of 13 survivors. CONCLUSIONS: In endemic areas,
      visceral leishmaniasis may complicate the clinical course of organ
      transplantation and can have fatal consequences, particularly when untreated.

PMID- 9625029
TI  - Recurrence of hemolytic-uremic syndrome in renal transplant recipients: a meta
      analysis.
AB  - BACKGROUND: Recurrence of hemolytic-uremic syndrome (HUS) in the allograft is
      associated with a very poor renal prognosis. Meta-analysis of previous trials may
      allow us to better estimate its real frequency, to identify risk factors for
      recurrence, and to predict the outcome of patients with definite recurrence.
      METHODS: An exhaustive search was conducted of HUS recurrence in renal
      transplantation from January 1977 to June 1997 using MEDLINE. RESULTS: Ten
      studies comprising 159 grafts in 127 patients were identified. The rate of
      recurrence was 27.8%. One-year graft survival was 76.6% in patients without
      recurrence and 33.3% in patients with recurrence (P<0.001). Older age at onset of
      HUS (16.96+/-7.6 years vs. 9.95+/-6.55 years; P<0.02), shorter mean interval
      between HUS and transplantation (2.51+/-2.7 years vs. 6.03+/-6.4 years; P<0.01),
      shorter mean interval between HUS and end-stage renal disease (0.79+/-0.39 years
      vs. 2.78+/-2.47 years; P<0.01), living-related donors, and the use of calcineurin
      inhibitors were associated with recurrence. CONCLUSION: Risk factors for HUS
      recurrence in renal transplantation could be identified through this meta
      analysis.

PMID- 9625030
TI  - Human herpesvirus-6 meningoencephalitis in a recipient of an unrelated allogeneic
      bone marrow transplantation.
AB  - BACKGROUND: Human herpesvirus-6 (HHV-6) has been implicated in bone marrow
      suppression, interstitial pneumonitis, and fatal meningoencephalitis in bone
      marrow transplant (BMT) recipients. METHODS: We describe the case of a woman with
      acute myeloid leukemia in second remission who developed febrile
      meningoencephalitis 8 months after a second unrelated BMT. RESULTS: Computed
      tomography and magnetic resonance images of the brain were nonspecific. Analysis
      of cerebrospinal fluid (CSF) revealed lymphocytosis and an increased protein
      level. Using polymerase chain reaction methods, HHV-6 was the only pathogen
      detected in CSF, peripheral blood mononuclear cells, and bone marrow. The patient
      was treated with ganciclovir and foscarnet for 3 months. All clinical
      manifestations resolved and HHV-6 polymerase chain reaction analysis of CSF
      became negative 40 days after the beginning of antiviral treatment. CONCLUSIONS:
      This observation strongly suggests that HHV-6 should be sought in BMT patients
      with neurological complications and that HHV-6 meningoencephalitis may respond to
      ganciclovir and foscarnet therapy.

PMID- 9625031
TI  - Diltiazem modulates monokine production in human mixed lymphocyte culture.
AB  - BACKGROUND: Calcium channel blockers are widely used in transplantation. Their
      immunosuppressive activity is well known and has been demonstrated both in vitro
      and in vivo. Nevertheless, their effect on cytokine production has never been
      reported. METHODS: One-way mixed lymphocyte cultures (MLCs) have been obtained
      from healthy human subjects. Cytokine production has been assessed by three
      different methods: by enzyme-linked immunosorbent assay on supernatants of MLC,
      by enzyme-linked immunospot method on MLC cells for measuring cytokine-producing
      cells, and by the reverse transcription polymerase chain reaction technique on
      MLC cells for measuring cytokine mRNAs. RESULTS: An interesting effect on
      proinflammatory monokines was observed: in this study, we demonstrate that the
      calcium antagonist diltiazem enhances interleukin-1beta and slightly reduces
      interleukin-6 production in MLC, but it has no effect on tumor necrosis factor
      alpha levels. CONCLUSION: For the first time, a modulation of monokine production
      by diltiazem can be demonstrated. This evidence suggests that calcium antagonist
      drugs may exert effects on monocytes and possibly on other antigen-presenting
      cells.

PMID- 9625032
TI  - Pulmonary fibrosis secondary to administration of mycophenolate mofetil.

PMID- 9625033
TI  - Comment on "Pregnancy after liver transplantation under tacrolimus" by Jain et
      al.

PMID- 9625034
TI  - Detection and characterization of monoclonal components in serum and urine.

PMID- 9625035
TI  - Ensuring accurate molecular genetic testing.

PMID- 9625036
TI  - AACC 50th anniversary retrospective. They use enzymes for everything! American
      Association for Clinical Chemistry.

PMID- 9625037
TI  - Calibrated user-friendly reverse transcriptase-PCR assay: quantitation of
      epidermal growth factor receptor mRNA.
AB  - We report a competitive reverse transcriptase-PCR (RT-PCR) assay and a calibrated
      user-friendly RT-PCR assay (CURT-PCR) for epidermal growth factor receptor (EGFR)
      mRNA. A calibrator was prepared from isolated rat liver RNA, and the amount of
      EGFR mRNA was determined by competitive RT-PCR. In CURT-PCR, a calibration curve
      was developed by plotting the ratio between the amount of PCR product originating
      from the calibrator and the RNA internal standard vs the amount of EGFR mRNA
      present in the calibrator. A fixed amount of RNA internal standard was
      coamplified with the EGFR mRNA present in the calibrator or in the sample, using
      the same primer set. The primers were chosen in regions of the EGFR mRNA that
      show 100% homology between human, rat, and mouse. The amount of EGFR in the
      unknown samples was calculated from the calibration curve based on the ratio
      between PCR product originating from the sample and the corresponding RNA
      internal standard. Competitive RT-PCR and CURT-PCR were used for rat liver
      samples from 21 different animals. Comparable results were obtained by the two
      methods. The imprecision of the CURT-PCR method was 8% (n = 20), and the
      imprecision of the traditional competitive RT-PCR was 16% (n = 17). We conclude
      that the CURT-PCR method developed is suitable for routine applications such as
      quantitation of EGFR expression in tumor biopsies. The imprecision is relatively
      low. Furthermore, the use of a calibration curve makes it possible to analyze a
      large number of samples in one analytical run and to accept or reject the results
      according to existing rules for quality assurance.

PMID- 9625038
TI  - Detection of tyrosinase mRNA in melanoma by reverse transcription-PCR and
      electrochemiluminescence.
AB  - Increased sensitivity and improved quantitation of analytical tests used in
      biotechnology and clinical chemistry are goals of many laboratories. We have used
      tyrosinase primers to specifically amplify by RT-PCR the tyrosinase mRNA
      expressed by the M12 melanoma cell line in a background of mRNA from breast
      cancer cells. An electrochemiluminescence detection procedure was used as a
      readout system for this study. Biotinylated post-PCR cDNA samples were hybridized
      to a tris(2,2'-bipyridine)ruthenium(II) (TBR) chelate-labeled oligonucleotide
      probe, and the hybrid was subsequently captured by streptavidin-coated Dynabeads.
      When either the QPCR System 5000 or the Origen 1 Analyzer System were used, the
      luminescence emitted by the TBR-chelate of the captured specific post-PCR product
      was assessed. Tyrosinase-specific mRNA isolated from approximately 1-10 melanoma
      cells in a background of 10(7) cells could be detected. We improved the
      sensitivity and logistics of the assay through the use of rTth for reverse
      transcription and amplification. Tyrosinase mRNA was detected in blood from 7 of
      16 melanoma patients, whereas none of the 5 healthy donor bloods were positive (P
      = 0.01; Wilcoxon test).

PMID- 9625039
TI  - Quantification of prostate-specific antigen mRNA by coamplification with a
      recombinant RNA internal standard and microtiter well-based hybridization.
AB  - We report a quantitative analytical methodology for prostate-specific antigen
      (PSA) mRNA, which is based on the coamplification of the target with a
      recombinant RNA internal standard (IS) using reverse transcriptase-polymerase
      chain reaction. PSA mRNA and the RNA IS contain the same primer recognition sites
      and generate amplification products that have identical sizes but differ in a 24
      bp sequence located in the center of the molecule. Amplified sequences are
      labeled with biotin using a biotinylated upstream primer. The products are
      captured on streptavidin-coated microtiter wells and hybridized to specific
      probes labeled with the hapten digoxigenin. The hybrids are determined using
      alkaline phosphatase-labeled anti-digoxigenin antibody and time-resolved
      fluorometry. The ratio of the fluorescence values obtained for the PSA mRNA and
      the RNA IS is a linear function of the amount of PSA mRNA present in the sample.
      Samples containing total RNA from PSA-expressing cells (LNCaP cells) in addition
      to 1 microg of RNA from healthy cells give fluorescence ratios related linearly
      to the number of cells in the range of 4 to 3000 cells.

PMID- 9625040
TI  - Urokinase plasminogen activator: a prognostic marker in breast cancer including
      patients with axillary node-negative disease.
AB  - Urokinase plasminogen activator (uPA) is a serine protease causally involved in
      cancer invasion and metastasis. In this study, high concentrations of uPA in
      primary breast cancers were independently associated with both a shortened
      disease-free interval and overall survival. For the disease-free interval as
      endpoint, uPA was a stronger indicator of outcome than lymph node status, whereas
      for overall survival, nodal status was stronger than uPA. In patients without
      metastasis to axillary nodes, uPA was also an independent prognostic marker,
      using both the disease-free interval and overall survival as end points. In
      contrast to uPA, neither tumor size nor estrogen receptor status was prognostic
      in the node-negative patients. Measurement of uPA concentrations might thus be of
      value in selecting the more aggressive subpopulation of node-negative breast
      cancer patients that could benefit from adjuvant therapy.

PMID- 9625041
TI  - Detection and identification of monoclonal gammopathies by capillary
      electrophoresis.
AB  - Capillary electrophoresis (CE) and immunosubtraction capillary electrophoresis
      (IS-CE) were compared with the conventional methods agarose gel electrophoresis
      (AGE) and immunofixation electrophoresis (IFE) for detection and identification
      of paraproteins. In total, 74 paraproteins out of 468 serum samples were detected
      by both methods. Seventy-three monoclonal bands with concentrations ranging from
      0.6 to 50.9 g/L were detected by the routine method. With CE, 70 paraproteins
      were detected and quantified on the electropherogram. Four paraproteins were not
      detected by CE; three of these were IgG (0.6, 1.1, and 2.2 g/L, respectively),
      and one was a IgM paraprotein (20.3 g/L) that could be visualized by minor
      changes in the running conditions. In comparison with IFE, 69 paraproteins were
      typed identically using IS-CE; only one paraprotein (IgMkappa, 14.9 g/L) could
      not be identified. On the other hand, a monoclonal IgA band that had not been
      detected by AGE was identified by CE and IS-CE. We conclude that, in general, CE
      could be a useful method for detection of paraproteins and that IS-CE is a good
      alternative to IFE. Additional studies are required to investigate the ionic
      strength and pH of the running buffer, because these prove to be the most crucial
      factors for routine CE separation of paraproteins.

PMID- 9625042
TI  - Sodium dodecyl sulfate-agarose gel electrophoresis of urinary proteins:
      application to multiple myeloma.
AB  - We evaluated a new sodium dodecyl sulfate-agarose gel electrophoresis (SDS-AGE)
      for urinary protein analysis in patients with multiple myeloma (MM; n = 47; ages,
      62 +/- 2 years, mean +/- SE). Abnormal proteinuria (mean = 1872 +/- 360 mg/24 h)
      was present in 95% of the samples; 75% of the patients had some sign of renal
      dysfunction (glomerular and/or tubular) according to their SDS-AGE pattern. A
      band suggesting Bence Jones proteinuria (BJP) was detected in 40 vs 33 specimens
      by routine AGE. Immunofixation identified BJP in 38 patients; the calculated
      sensitivity of SDS-AGE for BJP was 97%. Excellent correlation (P <0.0001) was
      obtained with routine AGE (r = 0.994) and immunonephelometry (r = 0.963) for
      light chain quantification. SDS-AGE allows easy evaluation of renal dysfunction
      and shows high sensitivity for BJP detection. In a specialized laboratory, it is
      useful for following the progress of MM patients through the semiquantification
      of BJP.

PMID- 9625044
TI  - Comparison of the Axis %CDT TIA and the CDTect method as laboratory tests of
      alcohol abuse.
AB  - Carbohydrate-deficient transferrin (CDT) has been suggested as a specific marker
      of alcohol abuse. We designed this study to compare the conventional CDTect
      method (Pharmacia & Upjohn) and the new semiautomated Axis %CDT turbidimetric
      immunoassay (%CDT TIA) for their diagnostic performance to identify problem
      drinking. The sensitivities of the %CDT TIA and CDTect for correctly classifying
      heavy drinkers (n = 90) were 29% and 59% with the thresholds currently
      recommended by the manufacturers, respectively. In the control group (n = 114),
      which included hospitalized patients with abnormal serum transferrin
      concentrations, the CDTect assay gave 21 false-positive values (18%), whereas the
      %CDT TIA showed 100% specificity. With the cutoff limits based on the present
      healthy control group (mean + 2 SD), the sensitivities of the %CDT TIA and CDTect
      were 61% and 86%, respectively. For men, the ROC plot area of the CDTect results
      in comparisons of alcohol abusers and healthy controls was significantly (P <
      0.05) higher than that of the %CDT TIA results, whereas for women, there was no
      significant difference in this respect. The slope and intercept (with 95%
      confidence intervals) for linear regression between CDTect and %CDT TIA were 0.13
      (0.12-0.15) and 1.16 (0.73-1.59), respectively (S(y/x) = 1.51, r = 0.744). CDTect
      results correlated positively with serum transferrin (r = 0.224, P < 0.001),
      whereas the %CDT TIA results showed a slight inverse correlation with serum
      transferrin (r = -0.132, P = 0.07). The data suggest that CDTect is more
      sensitive than %CDT TIA in detecting drinking problems. However, the %CDT TIA
      method yields more specificity when analyzing samples from patients with high
      serum transferrin concentrations.

PMID- 9625043
TI  - Characterization of cardiac troponin subunit release into serum after acute
      myocardial infarction and comparison of assays for troponin T and I. American
      Association for Clinical Chemistry Subcommittee on cTnI Standardization.
AB  - We examined the release of cardiac troponin T (cTnT) and I (cTnI) into the blood
      of patients after acute myocardial infarction (AMI). Three postAMI serum samples
      were applied in separate analytical runs onto a calibrated gel filtration column
      (Sephacryl S-200), and the proteins were separated by molecular weight. Using
      commercial cTnT and cTnI assays measured on collected fractions, we found that
      troponin was released into blood as a ternary complex of cTnT-I-C, a binary
      complex of cTnI-C, and free cTnT, with no free cTnI within the limits of the
      analytical methodologies. The serum samples were also examined after incubation
      with EDTA and heparin. EDTA broke up troponin complexes into individual subunits,
      whereas heparin had no effect on the assays tested. We added free cTnC subunits
      to 24 AMI serum samples and found no marked increase in the total cTnI
      concentrations, using an immunoassay that gave higher values for the cTnI-C
      complex than free cTnI. To characterize the cross-reactivity of cTnT and cTnI
      assays, purified troponin standards in nine different forms were prepared, added
      to serum and plasma pools, and tested in nine quantitative commercial and pre
      market assays for cTnI and one approved assay for cTnT. All nine cTnI assays
      recognized each of the troponin I forms (complexed and free). In five of these
      assays, the relative responses for cTnI were nearly equimolar. For the remainder,
      the response was substantially greater for complexed cTnI than for free cTnI.
      Moreover, there was a substantial difference in the absolute concentration of
      results between cTnI assays. The commercial cTnT assay recognized binary and
      ternary complexes of troponin on a near equimolar basis. We conclude that all
      assays are useful for detection of cardiac injury. However, there are differences
      in absolute cTnI results due to a lack of mass standardization and heterogeneity
      in the cross-reactivities of antibodies to various troponin I forms.

PMID- 9625045
TI  - Novel immunoassay for the measurement of complexed prostate-specific antigen in
      serum.
AB  - Serum prostate-specific antigen (PSA) is an effective diagnostic tool for
      detection of prostate cancer (CaP) at an early and potentially curable stage, but
      specificity is low. Studies have shown that the proportion of serum PSA complexed
      with alpha-1-antichymotrypsin (ACT) is higher in men with CaP than in men with
      benign prostate disease. We developed a novel immunoassay for complexed PSA based
      on the unique binding properties of a monoclonal antibody that fails to bind free
      PSA in the presence of antibodies specific for free PSA. The assay measured
      mixtures of free and complexed PSA accurately, and the measured values of free +
      complexed PSA in artificial mixtures and in patient sera were equivalent to the
      measured value of total PSA. Both the serum concentration and the proportion of
      complexed PSA was substantially higher in patients with CaP compared with
      patients with benign prostate disease. The cPSA assay may have utility in
      improving specificity in screening for prostate cancer.

PMID- 9625046
TI  - Remnant lipoprotein cholesterol and triglyceride reference ranges from the
      Framingham Heart Study.
AB  - Remnants of triglyceride-rich lipoproteins of both intestinal and liver origin
      are considered atherogenic, but they have been difficult to isolate and measure.
      An assay has been developed that allows the measurement of remnant-like particle
      cholesterol (RLP-C) and triglyceride (RLP-TG). RLP-C and RLP-TG concentrations
      were measured in >3000 fasting plasma samples obtained from participants in exam
      cycle 4 of the Framingham Offspring Study and stored at -80 degrees C. After
      exclusions, comparisons were made for 2821 samples (1385 women, 1436 men; mean
      age, 52 years). For women, the mean RLP-C and RLP-TG values were 0.176 +/- 0.058
      mmol/L (6.8 +/- 2.3 mg/dL) and 0.204 +/- 0.159 mmol/L (18.1 +/- 14.1 mg/dL),
      respectively; for men, the mean values were 0.208 +/- 0.096 mmol/L (8.0 +/- 3.7
      mg/dL) and 0.301 +/- 0.261 mmol/L (26.7 +/- 23.1 mg/dL), respectively. Women had
      significantly lower RLP-C and RLP-TG values (P <0.0001) than men; premenopausal
      women had significantly lower values than postmenopausal women (P <0.0001); and
      younger subjects (<50 years) had significantly lower values than older
      individuals (P <0.0001). The 75th percentile values for RLP-C and RLP-TG were
      0.186 mmol/L (7.2 mg/dL) and 0.225 mmol/L (19.9 mg/dL), respectively, for women,
      and 0.225 mmol/L (8.7 mg/dL) and 0.346 mmol/L (30.6 mg/dL) for men. These data
      provide reference ranges for use in the evaluation of RLP-C and RLP-TG as
      potential indicators of risk for coronary heart disease.

PMID- 9625047
TI  - Evaluation of a homogeneous assay for high-density lipoprotein cholesterol:
      limitations in patients with cardiovascular, renal, and hepatic disorders.
AB  - We evaluated the performance of a homogeneous assay for the automated measurement
      of high-density lipoprotein cholesterol (HDL-C) and compared it with a
      conventional precipitation technique in the following groups of people: control
      subjects (group A), clinically-healthy elderly (group B), myocardial infarction
      patients (group C), nephrotic syndrome patients (group D), and liver cirrhosis
      patients (group E). The performance of the technique was acceptable with respect
      to precision, accuracy, linearity, and detection limit. Triglycerides up to 40
      mmol/L and bilirubin up to 150 micromol/L did not cause interferences. Hemoglobin
      decreased HDL-C measurements. Samples were stable at -20 degrees C for up to four
      months. Bland-Altman plots showed a good agreement between both techniques in the
      control group but with a progressive divergence in the patient groups B to E.
      Results indicate limitations of the technique in certain clinical conditions and,
      coincidentally, the need for reliable calibration materials.

PMID- 9625048
TI  - Analytical and clinical performance of a homogeneous enzymatic LDL-cholesterol
      assay compared with the ultracentrifugation-dextran sulfate-Mg2+ method.
AB  - LDL-cholesterol (LDL-C) concentration is currently determined in most clinical
      laboratories by the Friedewald calculation. This approach has several limitations
      and may not meet the current total error requirement in LDL-C measurement of < or
      = 12%. We evaluated the analytical and clinical performance of the direct N
      geneous LDL-C assay (Equal Diagnostics). The N-geneous method correlated highly
      with the modified beta-quantification assay (r = 0.95; y = 0.91x + 70.6 mg/L; n =
      199), showed no significant effect of increased triglyceride or other common
      interferants, and performed adequately in serum samples from nonfasting
      individuals. This assay demonstrated a mean total error of 6.75% over a wide
      range of LDL-C concentrations. In addition, at the medical decision cutoff
      points, this LDL-C assay showed positive predictive values of 78-95% and negative
      predictive values of 84-99%. We conclude that the N-geneous LDL-C meets the
      currently established analytical performance goals and appears to have a role in
      the diagnosis and management of hypercholesterolemic patients.

PMID- 9625049
TI  - Determination of ciprofloxacin in plasma and urine by HPLC with ultraviolet
      detection.
AB  - A simple, sensitive isocratic method for the detection and quantification of
      ciprofloxacin in plasma and urine has been developed. The assay consisted of
      reversed-phase HPLC with ultraviolet detection. Plasma proteins were removed by a
      fast and efficient procedure. For the urine samples, the only required sample
      preparation was dilution. Separation was achieved on a C18 reversed-phase column.
      The quantification limit was 0.01 mg/L in plasma and 0.5 mg/L in urine. This
      method was sufficiently sensitive for pharmacokinetic studies.

PMID- 9625050
TI  - Paraquat-induced renal injury studied by 1H nuclear magnetic resonance
      spectroscopy of urine.
AB  - The herbicide paraquat (1,1'-dimethyl-4,4'-bipyridylium dichloride; PQ), is a
      poison known to cause delayed mortality due to lung and kidney injuries. High
      resolution proton nuclear magnetic resonance (1H NMR) spectroscopy has been
      extensively applied in evaluating nephrotoxicity by the characteristic
      perturbations in the excretion pattern of low molecular weight endogenous
      metabolites. The application of the method allows the rapid localization of the
      renal injury noninvasively. In this study, we report 1H NMR and conventional
      clinical chemistry urinalysis in two patients suffering from paraquat
      intoxication after overdose with suicidal intent. The alterations in the urine
      NMR spectrum suggest necrosis of the pars recta of the proximal renal tubules.
      The molecule of paraquat is also clearly detected in the same spectrum. In
      conclusion, the rapid screening of urine by NMR spectroscopy provides information
      about both the identity of the poison and the abnormal pattern of endogenous
      metabolites that characterize the location of the injury in renal tubules and
      reveals alterations in unusual metabolites that are not commonly measured.

PMID- 9625051
TI  - Low percentage of aluminoxamine and ferrioxamine in uremic serum after
      desferrioxamine administration.
AB  - HPLC was used to study the effectiveness of two different desferrioxamine (DFO)
      administration strategies (15 mg/kg DFO, 1 h or 44 h before dialysis) on
      generation of aluminoxamine and ferrioxamine in five hemodialysis patients. The
      percentage of ultrafilterable aluminum and iron in these patients was also
      investigated by electrothermal atomic absorption spectrometry. The administration
      of DFO in both schemes increased the ultrafilterable serum aluminum
      concentrations from a mean of 17.1 +/- 1.6% to a mean of 75.7 +/- 14.1%. However,
      1 h after DFO infusion, only 38.8 +/- 7.7% of the total serum aluminum was bound
      to DFO; 44 h after DFO infusion, only 15.8 +/- 8.0% was bound. Similar results
      were obtained for ferrioxamine. These results suggest that the ultrafilterable
      serum fraction contains aluminum and iron chelated by DFO and by DFO metabolites,
      which retain similar metal-chelating abilities.

PMID- 9625052
TI  - Determination of monoethylglycinexylidide by fluorescence polarization
      immunoassay in highly icteric serum samples: modified precipitation procedure and
      HPLC compared.
AB  - Hyperbilirubinemia, which frequently occurs in severe liver disease, interferes
      with the fluorescence polarization immunoassay (FPIA) monoethylglycinexylidide
      (MEGX) assay manufactured by Abbott Diagnostics. Because the MEGX test is
      particularly helpful in this clinical situation, strategies have been developed
      to overcome this problem. Precipitation of serum with the Abbott Digoxin II
      precipitation reagent eliminates bilirubin. Therefore, we compared FPIA results
      after precipitation of 81 icteric samples from 27 MEGX tests to results obtained
      using a validated HPLC method. The precipitation did not substantially alter the
      performance characteristics of FPIA: detection limit, 8 microg/L; between-days
      imprecision, 5.3-6.2%; recovery, 102-104% (50-200 microg/L). This pretreatment of
      serum did not eliminate all interference, and only a poor correlation was
      observed between serum MEGX concentrations measured with HPLC or modified FPIA
      (r2 = 0.46; S(y/x) = 20.0 microg/L). In contrast, MEGX formation values
      calculated by subtraction of the prelidocaine MEGX concentration were in close
      agreement (r2 = 0.98; S(y/x) = 2.3 microg/L). Because only MEGX formation is
      clinically relevant, this modified FPIA procedure offers a simple and rapid
      alternative to HPLC.

PMID- 9625053
TI  - Automated simultaneous quantification of the immunosuppressants 40-O-(2
      hydroxyethyl) rapamycin and cyclosporine in blood with electrospray-mass
      spectrometric detection.
AB  - A new analytical method to quantify 40-O-(2-hydroxyethyl)rapamycin (SDZ RAD) and
      cyclosporine (Cs) simultaneously in blood is presented. The combination of an on
      line solid-phase extraction step with an HPLC system coupled to an electrospray
      mass spectrometer gave excellent specificity, sensitivity, and reproducibility.
      Aliquots of deproteinized blood samples were injected into the HPLC system and
      extracted on-line, using a conventional C18 guard column. The extract was eluted
      from the guard column in the backflush mode and injected into the liquid
      chromatography-mass spectrometry system. The calibration functions for SDZ RAD
      and Cs extracted from blood with added analyte were linear from 0.15 to 30
      microg/L (r2 = 0.999) and from 1.5 to 1000 microg/L (r2 = 0.999), respectively.
      The CVs of peak areas were 6.2% at 10 microg/L SDZ RAD (n = 6) and 6.2% at 100
      microg/L Cs (n = 6). Recovery ranged from 84.3% to 102.3% for SDZ RAD and from
      81.7% to 92.2% for Cs. The lower limit of detection for both drugs was 0.05
      microg/L. A rate of four samples per hour was maintained during the consecutive
      analysis of SDZ RAD and Cs in >500 blood samples with one single extraction and
      analytical column. The method described is a powerful tool for the simultaneous
      determination of SDZ RAD and Cs in blood. It works without time-consuming sample
      preparation steps and with excellent reproducibility. Because of the detection
      performance of electrospray mass spectrometry, this system offers flexibility in
      the working range, which is essential for therapeutic drug monitoring under
      different conditions.

PMID- 9625054
TI  - Predictive value of determinations of zinc protoporphyrin for increased blood
      lead concentrations.
AB  - Blood lead (PbB) and red cell zinc protoporphyrin (ZPP) concentrations are widely
      used biomarkers for lead toxicity. It is uncertain, however, whether either or
      both are needed for monitoring lead exposure and how discordant PbB and ZPP
      values should be interpreted. We reviewed the results of PbB and ZPP
      determinations in 94 workers in a lead-battery plant over a 13-year period and
      retrieved all 807 sets of tests in which both PbB and ZPP were available, with a
      follow-up PbB value 6 months later. PbB exceeded 1.93 micromol/L (40 microg/dL)
      in 414 (51%), and 2.90 micromol/L (60 microg/dL) in 105 (14%) of the blood
      samples. We derived the test properties of various ZPP concentrations for
      concurrent "toxic" PbB concentrations, defined as > or = 1.93 and 2.90 micromol/L
      (40 and 60 microg/dL). The results indicated that, given a population of lead
      exposed workers with a 10% prevalence of PbB of > or = 2.90 micromol/L (60
      microg/dL), a policy of testing PbB only in those with ZPP > 0.71 micromol/L (40
      microg/dL) would obviate 42% of the PbB tests, but would miss about three cases
      with toxic PbB concentrations in every 200 workers at risk. A finding of
      increased ZPP concentrations with a concurrent "nontoxic" PbB was associated with
      an increased risk of a toxic PbB concentration 6 months later. We conclude that
      (a) screening by testing only ZPP does not safeguard exposed persons against lead
      toxicity, and (b) the frequency of PbB monitoring should be guided by estimates
      of the risk of future lead toxicity in individual workers.

PMID- 9625055
TI  - Marked gender differences in ambulatory morning growth hormone values in young
      adults.
AB  - The influence of gender on serum concentrations of growth hormone (GH) and 12
      other endocrine analytes was investigated in sera drawn from 291 healthy medical
      students in the ambulatory state in the morning, after fasting overnight. GH was
      measured with a sensitive noncompetitive fluoroimmunoassay. The median GH value
      was 80-fold higher in women 21-26 years old than in age-matched men (14.4 vs 0.18
      mIU/L), compared with a female/male ratio of 2.2 for 17beta-estradiol and a
      male/female ratio of 14 for testosterone. Furthermore, the values for sex hormone
      binding globulin, follicle-stimulating hormone, luteinizing hormone, prolactin,
      and insulin-like growth factor 1 (IGF-1) were higher, whereas the values for free
      thyroxine, triiodothyronine, thyroid-stimulating hormone, and parathyroid hormone
      were lower in the women. The median GH value was 68-fold higher in women 27-43
      years old than in age-matched men (10.9 vs 0.16 mIU/L). Women taking
      contraceptives with ethinyl estradiol and desogestrel or levonorgestrel had
      higher GH values, and the desogestrel group had lower IGF-1 values than women not
      taking contraceptives. The median GH values in these groups were 125- and 117
      fold higher, respectively, than in men 21-26 years old. The results suggest that
      routine morning activity produces a marked GH response in >90% of young women but
      in very few age-matched men. The effect on GH was even more pronounced in women
      taking oral contraceptives, suggesting that the intake of ethinyl estradiol
      contributes to higher GH concentrations in these women.

PMID- 9625056
TI  - Hemoglobin Raleigh as the cause of a falsely increased hemoglobin A1C in an
      automated ion-exchange HPLC method.
AB  - Irreversible glycation of the hemoglobin A0 (HbA0) beta chain leads to the
      production of HbA1C, which can be used to monitor long-term blood glucose control
      in patients with diabetes mellitus. HbA1C is less positively charged than
      nonglycated HbA0, and this decrease in charge is the basis of ion-exchange and
      electrophoretic methods that measure HbA1C. We recently identified a sample that
      appeared to contain 46% HbA1C by an automated ion-exchange HPLC method (Bio-Rad
      Variant) but only 3.8% by an immunoinhibition latex agglutination method. A
      combination of traditional and mass spectrometric protein analysis and genomic
      DNA analysis of the Hb beta chain and genes revealed that the patient was
      heterozygotic for Hb-Raleigh, a variant containing a valine-->alanine
      substitution at position 1 of the beta chain. The amino-terminal alanine in this
      variant Hb is posttranslationally modified by acetylation, leading to a charge
      difference similar to glycation and making the behavior of HbA1C and Hb Raleigh
      virtually identical in the ion-exchange HPLC method. This observation suggests
      that it is important to confirm HbA1C values in excess of 15%, especially if they
      are not consistent with the clinical picture, by an independent HbA1C method such
      as immunoassay or boronic acid affinity chromatography. However, for this
      particular variant Hb, even these latter methods might be misleading, because the
      acetylated N-terminal amino acid of the Hb-Raleigh beta chain cannot be glycated.

PMID- 9625057
TI  - Non-separation assay for glycohemoglobin.
AB  - The determination of glycohemoglobin [HbA1c, HbA1, or total glycohemoglobin
      (GHb)] has become an established procedure in the management of diabetes
      mellitus. Here, we describe the development of a simple, fluorescence, non
      separation assay for the percentage of GHb (%GHb). The fluorescence of an eosin
      boronic acid derivative when it was mixed with hemolysates of unwashed
      erythrocytes was quenched in proportion to the percentage of glycohemoglobin.
      Measurement of the fluorescence intensity gave an estimate of GHb in the sample,
      and measurement of light absorbance gave an estimate of total hemoglobin. A
      combination of the two measurements gave the assay response. Comparison with HPLC
      (Menarini-Arkray HA-8140 fully automated analyzer) for the percentage of HbA1
      (%HbA1) gave %GHb(NETRIA) = 1.1(SD +/-0.03)%HbA1 +0.6(SD +/-0.3), S(y/x) = 0.821,
      r = 0.972, n = 80; comparison for HbA1c gave %GHb(NETRIA) = 1.3(SD +/-0.04)%HbA1c
      + 1.8(SD +/-0.3), S(y/x) = 0.813, r = 0.973, n = 80. Precision, estimated as the
      percentage of the CV of the %GHb assay results, was <2% (intraassay, range 5-22%
      GHb) and <4.2% (interassay, range 4-16% GHb). Dilution of a high-percentage GHb
      sample lysate showed that the assay was linear, and addition of glucose (60
      mmol/L), bilirubin (250 micromol/L), and triglycerides (14 mmol/L) to low,
      medium, and high %GHb samples showed no clinical interference in assay results.

PMID- 9625058
TI  - Comparison of different analytical methods for assessing total antioxidant
      capacity of human serum.
AB  - Three assays were compared for the determination of total antioxidant capacity in
      human serum: the oxygen radical absorbance capacity (ORAC) assay, the Randox
      Trolox-equivalent antioxidant capacity (Randox-TEAC) assay, and the ferric
      reducing ability (FRAP) assay. There was a weak but significant linear
      correlation between serum ORAC and serum FRAP. There was no correlation either
      between serum ORAC and serum TEAC or between serum FRAP and serum TEAC. The
      effect of dilution on the serum TEAC value and the use of inhibition percentage
      at a fixed time, without considering the length of inhibition time in the
      quantitation of results, adversely affected the Randox-TEAC assay. The FRAP assay
      is simple and inexpensive but does not measure the SH-group-containing
      antioxidants. The ORAC assay has high specificity and responds to numerous
      antioxidants. By utilizing different extraction techniques in the ORAC assay, one
      can remove serum proteins and also make some gross differentiation between
      aqueous and lipid-soluble antioxidants. However, the ORAC assay requires
      approximately 60 min more than the FRAP or Randox-TEAC assay to quantitate
      results.

PMID- 9625059
TI  - Development and validation of an automated latex-enhanced immunoassay for
      prealbumin.
AB  - The measurement of circulating prealbumin has been shown to be clinically useful
      in the assessment of nutritional status, both as an initial screen and in the
      monitoring of nutritional recovery. We describe a fully automated,
      noncompetitive, homogeneous, light-scattering immunoassay that has been developed
      for this analyte on a Dimension (Dade) analyzer. A sheep anti-prealbumin IgG
      fraction was covalently coupled to 40-nm chloromethyl styrene particles and,
      after the addition of sample, polyethylene glycol-assisted immunoagglutination
      was monitored by turbidimetry. The prealbumin working assay range was 8-550 mg/L
      at a sample volume of 2 microL and a reaction time of 6.5 min. When data were
      analyzed using ANOVA, total and within-run assay imprecision values (CVs) were 1
      5%, and calibration and reagent stabilities were in excess of 40 days. Mean
      analytical recoveries were 102% +/- 4% (SD), and there was no lack of
      parallelism. Hemolysis, lipemia, and bilirubin did not interfere. Both plasma
      anticoagulated with heparin or EDTA and serum from plain or serum-separation
      tubes were acceptable as sample matrices. Comparison with the Beckman Array
      method gave a Passing and Bablok regression of: Dimension analyzer = 1.01Beckman
      + 7.1 (n = 103), using a common calibrator. We conclude that the prealbumin
      method is appropriate for clinical use according to the analytical criteria used
      in this study.

PMID- 9625060
TI  - Effect of serum-clot contact time on clinical chemistry laboratory results.
AB  - The effect of serum-clot contact time on laboratory results was studied by
      dividing each blood specimen into four blood collection tubes. The control sera
      were separated from the clot within 30 min of the collection. The other tubes
      were incubated at 32 degrees C, and the sera were separated at 3, 6, and 24 h.
      The sera were stored at 4 degrees C and analyzed at the same time. The stability
      of the tests was determined by comparing the results of the 3-, 6-, and 24-h
      samples with the values from the 30-min samples. The acceptable limits around the
      30-min values were derived from the analytical and intraindividual biological
      variation of the tests. A total of 63 analytes were studied. Potassium,
      phosphorous, and glucose were the least stable, and the serum should be separated
      from the clot within 3 h for these analytes. Albumin, bicarbonate, chloride, C
      peptide, HDL-cholesterol, iron, LDL-cholesterol, and total protein should be
      separated within 6 h. The other analytes were stable for 24 h of serum-clot
      contact.

PMID- 9625061
TI  - Correlation of plasma concentrations of cystatin C and creatinine to inulin
      clearance in a pediatric population.
AB  - Measurement of blood concentrations of cystatin C (cysC), a cysteine protease
      inhibitor present in human plasma, has been suggested for use as an indicator of
      glomerular filtration rate (GFR) in a manner analogous to the use of plasma
      creatinine (SCR). In this study, cysC and SCR were measured in plasma from
      pediatric patients (4-19 years) with renal disease for whom a "gold standard"
      measurement of GFR via inulin clearance (C(IN)) was available. The data analyses
      were divided into two age groups: group A (4-12 years, n = 26) and group B (12-19
      years, n = 34). For both age groups, the linear correlation coefficient of
      [cysC](-1) vs C(IN) (mL/min/1.73 m2) (r = 0.765 for group A and r = 0.869 for
      group B) was less than that of the linear correlation coefficient of [SCR](-1) vs
      C(IN) (r = 0.841 for group A and r = 0.892 for group B). As a single measurement
      for detection of abnormal GFR, however, the optimum receiver-operator
      characteristic point for cysC measurement (for group A at cysC >1.2 mg/L,
      sensitivity = 80%, specificity = 91%; and for group B at cysC >1.4 mg/L,
      sensitivity = 87%, specificity = 100%) was numerically superior to that for SCR
      measurement (for group A at SCR >8.0 mg/L, sensitivity = 67%, specificity = 100%;
      and for group B at SCR >9.0 mg/L, sensitivity = 91%, specificity = 91%), using a
      reference value for normal GFR of C(IN) > 90 mL/min/1.73 m2. However, these
      differences were not statistically significant. CysC measurement appears to be
      broadly equivalent to SCR measurement for estimation of GFR in pediatric
      patients.

PMID- 9625062
TI  - Vitros digoxin immunoassay evaluated for interference by digoxin-like
      immunoreactive factors.

PMID- 9625063
TI  - Quantitative determination of short-chain organic acids in urine by capillary
      electrophoresis.

PMID- 9625064
TI  - Increased serum procalcitonin in newborn infants without infection.

PMID- 9625065
TI  - Quantitative analysis of the human epidermal growth factor receptor messenger RNA
      using reverse transcription-PCR: a methodological study of imprecision.

PMID- 9625066
TI  - Clinical evaluation of the CF(12)m cystic fibrosis DNA diagnostic kit.

PMID- 9625067
TI  - Cardiac troponin T by Elecsys system and a rapid ELISA: analytical sensitivity in
      relation to the TropT (CardiacT) "bedside" test.

PMID- 9625068
TI  - A highly sensitive enzyme-amplified lanthanide luminescence immunoassay for
      interleukin 6.

PMID- 9625069
TI  - Determination of angiotensin-converting enzyme gene polymorphisms: stepdown PCR
      increases detection of heterozygotes.

PMID- 9625070
TI  - Multicenter evaluation of PCR methods for the detection of factor V Leiden
      (R506Q) genotypes.

PMID- 9625071
TI  - Rapid automated high sensitivity enzyme immunoassay of C-reactive protein.

PMID- 9625072
TI  - Prostate-specific antigen expression in neuroblastoma cell lines.

PMID- 9625073
TI  - Hybrid capture.

PMID- 9625074
TI  - Determination of urinary oxalate with CI- and NO3- insensitive oxalate oxidase
      purified from sorghum leaf.

PMID- 9625075
TI  - The mutation G20210-->A in the prothrombin gene is a strong risk factor for
      pulmonary embolism.

PMID- 9625076
TI  - The value of free enterprise.

PMID- 9625077
TI  - Weekly iodine supplements work.

PMID- 9625078
TI  - There needs to be more than one way to skin the iodine deficiency disorders cat:
      novel insights from the field in Zimbabwe.

PMID- 9625079
TI  - Dietary fat controversy: is it also applicable to children?

PMID- 9625080
TI  - Sunlight, season, skin pigmentation, vitamin D, and 25-hydroxyvitamin D: integral
      components of the vitamin D endocrine system.

PMID- 9625081
TI  - Childhood obesity and adult cardiovascular mortality: a 57-y follow-up study
      based on the Boyd Orr cohort.
AB  - Few studies have examined associations between childhood overweight and adult
      disease. We examined the relation between BMI measured in childhood and adult all
      cause and cardiovascular mortality in a 57-y follow-up of a cohort study based on
      the Carnegie (Boyd Orr) Survey of Family Diet and Health in prewar Britain (1937
      1939). Complete baseline and follow-up data were available for 1165 males and
      1234 females who were aged between 2 y and 14 y 9 mo when they were examined. All
      cause and cardiovascular mortality were associated with higher childhood BMIs.
      Compared with those with BMIs between the 25th and 49th centiles, the hazard
      ratio (95% CI) for all-cause mortality in those above the 75th BMI centile for
      their age and sex was 1.5 (1.1, 2.2) and for ischemic heart disease it was 2.0
      (1.0, 3.9). There was also a suggestion of a nonlinear association with overall
      mortality; those in the 25-49th centile of the BMI distribution had the lowest
      mortality rates. The linear associations may be due in part to the tracking of
      BMI between childhood and adulthood. High BMI in adults is known to be associated
      with raised blood pressure and abnormal lipid profiles. The relative
      contributions of adult and childhood overweight to the observed mortality
      patterns are uncertain. From the public health perspective, strategies aimed at
      reducing weight in childhood are important but may only affect adult health if
      such weight reduction persists into adulthood.

PMID- 9625082
TI  - Familial predisposition for obesity may modify the predictive value of serum
      leptin concentrations for long-term weight change in obese women.
AB  - Leptin is believed to play a role in regulating food intake and body weight. The
      aim of this study was to examine the influence of parental history of obesity on
      the association between baseline serum leptin concentrations and subsequent 4-y
      weight changes. Changes in food intake were also considered in the analysis.
      Middle-aged, obese women with no obese parent (n = 25) or at least one obese
      parent (n = 24) were included in the analysis. At baseline, women with no
      parental history of obesity and women with a parental history of obesity did not
      differ in body mass index (in kg/m2: 41.2 and 40.2, respectively) or median
      leptin concentrations (40.8 and 38.8 microg/L, respectively). Four-year weight
      changes varied widely in both groups combined (from -30 to 24 kg). Stratified
      regression analysis, adjusted for age, weight, and height, revealed that high
      leptin concentrations predicted less weight gain (or more weight loss) in women
      with no obese parent (beta = -21.2, P = 0.0006) but played no significant role in
      predicting weight gain in women with at least one obese parent (beta = -3.8, P =
      0.41). Adding changes in energy and fat intakes to the model reduced the
      association between leptin and weight change to nonsignificance in the women with
      no obese parent, indicating that the effect of leptin could be explained largely
      by dietary changes. In conclusion, serum leptin concentrations predict long-term
      weight change in obese women with no history of parental obesity, an association
      largely mediated by changes in food intake.

PMID- 9625083
TI  - Decreased mitogen response of splenic lymphocytes in obese Zucker rats is
      associated with the decreased expression of glucose transporter 1 (GLUT-1).
AB  - We reported previously that obesity is a risk factor for deteriorating cellular
      immune functions in aging. However, the mechanism by which obesity decreases
      cellular immunity remains to be elucidated. To determine the mechanism of the
      decrease in cellular immunity with obesity, lean (Fa/?) and obese (fa/fa) 12-mo
      old Zucker rats were used. The mitogen response of splenic lymphocytes in obese
      Zucker rats was significantly lower than that of lean Zucker rats, which was not
      restored by in vitro treatment with indomethacin (10 micromol/L), an inhibitor of
      prostaglandin E2 (PGE2). In addition, PGE2 production by splenic lymphocytes was
      not greater in obese than in lean Zucker rats. Glucose consumption by splenic
      lymphocytes after in vitro incubation with concanavalin A (conA) for 48 h was
      also significantly lower in obese Zucker rats. Expression of glucose transporter
      1 (GLUT-1), analyzed by Western blot analysis, was lower in splenic lymphocytes
      of obese than in lean Zucker rats. However, the expression of the conA receptor
      in splenic lymphocytes, analyzed by flow cytometry with fluorescein
      isothiocyanate-conjugated conA, was not significantly different between lean and
      obese Zucker rats. In conclusion, the decreased mitogen response of splenic
      lymphocytes in obese Zucker rats may be due in part to the decreased uptake of
      glucose as the main energy source for lymphocytes at the stage of proliferation
      and may be associated with the decreased expression of GLUT-1.

PMID- 9625084
TI  - Parents as the exclusive agents of change in the treatment of childhood obesity.
AB  - BACKGROUND: Excessive weight in childhood is a serious public health concern
      because of its costly health consequences and its increasing prevalence.
      OBJECTIVE: Our objective was to compare the efficacy of a family-based approach
      for the treatment of childhood obesity, in which the parents served as the
      exclusive agents of change, with that of the conventional approach, in which the
      children served as the agents of change. DESIGN: This study had a randomized,
      longitudinal prospective design and lasted 1 y. Sixty obese children aged 6-11 y
      were randomly allocated to the experimental (parents as agents of change) or
      control (children as agents of change) group. Anthropometric and biochemical
      measurements were determined at the start and end of the study. A
      sociodemographic questionnaire and a family eating and activity habits
      questionnaire were completed by both parents. Hour-long support and educational
      sessions were conducted by a clinical dietitian: 14 sessions for the parents in
      the experimental group and 30 sessions for the children in the control group.
      RESULTS: The dropout rate was nine times greater in the control group (n = 9)
      than in the experimental group (n = 1). Mean percentile weight reduction was
      significantly (P < 0.03) higher in children in the experimental group (14.6%)
      than in the control group (8.1%). CONCLUSIONS: Treatment of childhood obesity
      with parents as the exclusive agents of change was superior to the conventional
      approach, as indicated by the dropout rate and the percentage weight loss of the
      children during the 1-y intervention.

PMID- 9625085
TI  - Fat distribution and hemostatic measures in obese children.
AB  - We examined the relation of general and visceral adiposity to plasma hemostatic
      factors [fibrinogen, D-dimer, and plasminogen activator inhibitor 1 (PAI-1)] in
      obese boys and girls 7-11 y of age (n = 41). Boys had significantly greater
      fibrinogen and D-dimer concentrations than girls (P < 0.05). whereas blacks had
      significantly greater fibrinogen and D-dimer concentrations than whites (P <
      0.05). Univariate analyses revealed that fibrinogen was positively associated
      with percentage body fat (%BF) (r = 0.42, P < 0.01), subcutaneous abdominal
      adipose tissue (SAAT) (r = 0.40, P < 0.01), total fat mass (r = 0.42, P < 0.01),
      and body mass index (r = 0.41, P < 0.01). PAI-1 was positively associated with
      visceral adipose tissue (VAT) (r = 0.49, P < 0.01), SAAT (r = 0.32, P < 0.05),
      fat-free mass (r = 0.50, P < 0.01), and insulin (r = 0.61, P < 0.001). D-Dimer
      was positively associated with %BF (r = 0.40, P < 0.01), SAAT (r = 0.37, P <
      0.05), total fat mass (r = 0.40, P < 0.01), and body mass index (r = 0.43, P <
      0.01). Multiple regression analysis revealed that for fibrinogen, sex and higher
      %BF explained significant independent portions of the variance. For PAI-1, higher
      amounts of VAT and fat-free mass were significant predictors. For D-dimer,
      ethnicity was a significant predictor. These results suggest that general
      adiposity and VAT may play a role in regulating plasma hemostatic factors in
      obese children. Even early in childhood, adiposity is associated with unfavorable
      concentrations of hemostatic factors that are in turn implicated in
      cardiovascular morbidity and mortality later in life.

PMID- 9625086
TI  - Clustering of cardiovascular disease risk factors among obese schoolchildren: the
      Taipei Children Heart Study.
AB  - BACKGROUND: Childhood obesity increases the risk of obesity in adulthood and is
      associated with cardiovascular disease (CVD) risk factors such as hypertension,
      diabetes mellitus, and dyslipidemia. OBJECTIVE: We evaluated the clustering of
      CVD risk factors among obese schoolchildren in Taiwan. DESIGN: After multistage
      sampling of 85 junior high schools in Taipei, we randomly selected 1366 children
      (681 boys and 685 girls) aged 13.3 y (range: 12-16 y). Anthropometric, blood
      pressure (BP), and biochemical CVD risk factors (including blood glucose, lipid,
      and lipoprotein concentrations) were measured. RESULTS: Boys had a higher body
      mass index, systolic BP, and glucose concentrations than girls and girls had
      higher lipid and lipoprotein concentrations than boys. After adjustment for age,
      obese boys had a significantly higher BP, ratio of total to HDL cholesterol, and
      glucose, cholesterol, triacylglycerol, HDL cholesterol, LDL cholesterol,
      apolipoprotein A-I, and apolipoprotein B concentrations than nonobese boys. BP,
      HDL cholesterol, LDL cholesterol, and ratio of total to HDL cholesterol were
      significantly different between nonobese and obese girls. Approximately 70% of
      obese boys had one and 25% had two or more CVD risk factors other than obesity.
      Obese girls had a significantly higher prevalence of high BP and a higher
      prevalence of CVD risk factor clustering than nonobese girls. CONCLUSIONS: Boys
      had higher glucose concentrations and BP and lower lipid concentrations than
      girls. We found an association between obesity and higher BP and between obesity
      and blood glucose and lipid concentrations for both sexes. Clustering of CVD risk
      factors was especially apparent among the obese children. A clustering of CVD
      risk factors may begin during early adolescence among the obese.

PMID- 9625087
TI  - Greater dietary intake of simple carbohydrate is associated with lower
      concentrations of high-density-lipoprotein cholesterol in hypercholesterolemic
      children.
AB  - Hypercholesterolemic children are increasingly being treated with lipid-lowering
      diets, but little research has focused on the effects of specific dietary
      substitutions on HDL cholesterol. We examined the relation between carbohydrate
      intake and HDL cholesterol in hypercholesterolemic children consuming fat
      restricted diets. We obtained 3-d food records for 67 children (mean age: 5.8 +/-
      2.5 y) referred for the treatment of hypercholesterolemia. Mean plasma HDL
      cholesterol was 1.12 +/- 0.21 mmol/L and total cholesterol was 5.99 +/- 1.39
      mmol/L. Dietary intake comprised (percentage of total energy) 24.9 +/- 5.1% fat,
      59.9 +/- 6.5% carbohydrate, and 16.5 +/- 3.4% protein. Carbohydrate intake
      included 30.7 +/- 7.4% from simple and 22.6 +/- 6.2% from complex carbohydrates.
      HDL cholesterol was positively correlated with intake of total fat (r = 0.44, P <
      0.001) and saturated fatty acids (r = 0.43, P < 0.001) and inversely correlated
      with intake of total carbohydrate (r = -0.55, P < 0.001) and simple carbohydrate
      (r = -0.40, P < 0.001), but not with complex carbohydrate (r = -0.02). The
      significant inverse relation between simple carbohydrate intake and HDL
      cholesterol remained after intakes of saturated, monounsaturated, and
      polyunsaturated fatty acids; intake of complex carbohydrates; dietary
      cholesterol; plasma triacylglycerol; and age were adjusted for with multivariate
      techniques. In summary, higher dietary intake of simple carbohydrates was
      associated with lower HDL-cholesterol concentrations in hypercholesterolemic
      children consuming reduced-fat diets.

PMID- 9625088
TI  - Comparison of existing skinfold equations for estimating body fat in African
      American and white women.
AB  - The purpose of this study was to compare seven skinfold equations with underwater
      weighing (UWW) for estimating body fat in 39 African American [age: 22.8 +/- 3.6
      y (x +/- SD); weight: 59.6 +/- 8.3 kg) and 39 white (age: 22.1 +/- 2.9 y; weight:
      61.7 +/- 7.3 kg) women. The hypothesis examined was that the equations would
      produce more accurate body fat estimates in white women, but would be appropriate
      for use in African American women. Body fat estimated from two quadratic, three
      linear, and two logarithmic skinfold equations was compared with body fat
      estimated from UWW; the same procedures were used to evaluate the results in both
      African Americans and whites. The data were analyzed by using t tests, analysis
      of variance, Scheffe's honestly significant difference tests, correlations, error
      assessments, and agreement. The results showed that total error, SEE, and SD
      values were larger in the African American women than in the white women and were
      not within acceptable limits listed in the literature. The correlation
      coefficients were lower in the African American women than in the white women.
      Agreement between the skinfold equations and UWW, based on deviations from mean
      differences, was better in the white women. In conclusion, the skinfold
      prediction equations evaluated in this study were more variable and produced more
      error when used in African American women. Therefore, population-specific
      equations for African American women should be used to estimate body fat because
      they will probably yield more accurate estimates.

PMID- 9625089
TI  - Energy expenditure, physical activity, and body composition of ambulatory adults
      with hereditary neuromuscular disease.
AB  - Persons with neuromuscular disease (NMD) have progressive weakness and wasting of
      skeletal muscle, reduced fat-free mass, and increased fat mass relative to
      healthy control subjects. To test the hypothesis that resting energy expenditure
      (REE), estimated total daily energy expenditure (TEE), and physical activity
      patterns are altered in ambulatory adults with NMD, 26 adult men and women with
      slowly progressive NMD and 19 able-bodied control subjects similar in age and
      weight were evaluated. REE was measured after an overnight fast by indirect
      calorimetry, TEE by heart rate monitoring, and body composition by air
      displacement plethysmography. REE was not significantly different between NMD and
      control subjects; however, TEE was significantly reduced in NMD subjects compared
      with control subjects, respectively (women: 7.8 +/- 1.5 compared with 10.5 +/-
      2.8; men: 10.2 +/- 3.6 compared with 12.7 +/- 2.6 MJ/d; P < or = 0.01),
      indicating that NMD subjects expended less energy in physical activity than did
      control subjects. NMD subjects also tended toward an increased energy cost of
      physical activity, particularly at higher activity levels (P = 0.06). Multiple
      regression analysis indicated that for all subjects combined, adiposity was
      positively associated with age and TEE and negatively associated with time spent
      in the active heart rate range and fat-free mass (P < or = 0.0001). This relation
      did not differ between NMD and control subjects, nor did it differ between men
      and women. We hypothesize that because of their reduced physical activity and
      increased adiposity, persons with NMD may be at risk for developing secondary
      conditions such as cardiovascular disease, hypertension, and diabetes.

PMID- 9625090
TI  - Volume of food consumed affects satiety in men.
AB  - This study tested the hypothesis that the amount (weight or volume) of food
      consumed affects the satiating potency of a food, independent of its energy
      content. Normal-weight young men (n = 20) were tested in a within-subjects
      design. Subjects were served a milk-based drink or no drink (control), followed
      30 min later by a self-selected lunch and > 4 h later by a self-selected dinner.
      Milk drinks were equal in energy content (2088 kJ, or 499 kcal) and had similar
      proportions of fat (30.3%), carbohydrate (54.7%), and protein (15%) across three
      volumes: 300, 450, and 600 mL. Ratings of palatability, sensory properties, and
      energy content of the drinks and of hunger completed before consumption of the
      preloads were not significantly different among conditions. The results showed
      that preload volume affected energy intake at lunch (P < or = 0.009) such that
      energy intake was less after the 600-mL preload than after the 300-mL preload.
      This effect was still present when energy intake at dinner was included (P < or =
      0.022). At lunch, including energy from the preload, subjects overate relative to
      the control condition (4323 +/- 322 kJ) after the 300- (5263 +/- 321 kJ) and 450
      mL (5011 +/- 300 kJ) preloads but not after the 600-mL (4703 +/- 353 kJ) preload.
      Thus, the best adjustment for the energy in the preloads was with the largest,
      least energy-dense drink. Consistent with the effects on intake, the volume of
      the drinks affected ratings of hunger and fullness. These results indicate that
      the volume consumed is an important determinant of satiety after milk drinks
      under these conditions.

PMID- 9625091
TI  - Effects of 14 d of covert substitution of olestra for conventional fat on
      spontaneous food intake.
AB  - We conducted a double-blind, placebo-controlled, within-subject crossover study
      to investigate the effects of covert substitution of olestra, a non-energy
      containing fat replacer, for conventional fat on food selection and energy intake
      in lean and obese men and women. Fifty-one subjects [BMI (kg/m2): 19-36; age: 25
      63 y] were studied during two 14-d treatment periods (olestra and placebo), with
      a 7-d washout between feeding periods. During the intervention periods all foods
      were provided to the subjects. The aim was to produce a 10% dilution of total
      energy intake by replacing conventional triacylglycerol with olestra. To
      accomplish this, subjects were required to consume core foods providing 20-35 g
      olestra (depending on estimated energy needs) or the same foods containing
      placebo triacylglycerol. Additional items could be selected from foods that
      varied in macronutrient composition. When the two treatment periods were
      compared, total energy intake was 8% lower and fat intake 11% lower during the
      olestra period than during the placebo treatment period (P < 0.0001). Overall,
      subjects compensated for 15% of the fat and 20% of the total energy replaced by
      olestra. In absolute terms, subjects consumed 32% of total energy from fat during
      the placebo period and 27% of total energy from fat during the olestra period.
      Neither carbohydrate nor protein intake (g/d) differed between periods. The
      results did not differ as a function of BMI (lean compared with obese) or sex.
      Over a 2-wk period, covert substitution of olestra for conventional fat led to
      reductions in dietary fat intake and total energy intake in all subjects.

PMID- 9625092
TI  - Acute effects on insulin sensitivity and diurnal metabolic profiles of a high
      sucrose compared with a high-starch diet.
AB  - Decreased insulin sensitivity is associated with diabetes mellitus, ischemic
      heart disease, and hypertension, both independently and in association as what is
      called the metabolic syndrome. Although the negative effects of obesity,
      sedentary lifestyles, and high-fat diets on insulin sensitivity are well
      established, the influence of type and quantity of dietary carbohydrate is more
      controversial. This study aimed to assess the acute (24 h) effects of a high
      sucrose compared with a high-starch diet on insulin sensitivity and to identify
      changes in blood metabolites that might lead to altered insulin sensitivity.
      Eight healthy adults consumed high-sucrose or high-starch diets (50% of dietary
      energy) in a randomized, crossover trial. Insulin sensitivity was assessed by a
      short insulin tolerance test the following morning. No differences were detected
      in insulin sensitivity, either for glucose metabolism [Kitt(glucose) (the rate
      constant for the decline in blood glucose concentrations) for sucrose diet =
      3.86%/min, for starch diet = 3.72%/min; pooled SEM = 0.23] or for lipid
      metabolism [Kitt(NEFA) (the rate constant for the decline in blood fatty acid
      concentrations) for sucrose diet = 12.9%/min, for starch diet = 11.4%/min; pooled
      SEM = 1.18]. Profiles for blood glucose and serum insulin concentrations revealed
      higher peaks and lower troughs with the high-sucrose diet whereas area under the
      curve for glucose was higher with the high-starch diet (6780 +/- 245 mmol x
      L/min) than with the high-sucrose diet (6290 +/- 283 mmol x L/min) (P < 0.001).
      Plasma fatty acid concentrations showed a late postprandial rise with the sucrose
      rich diet relative to the starch-rich diet, which was mirrored with a
      fractionally later peak in triacylglycerol concentrations.

PMID- 9625093
TI  - Satiating effect of proteins in healthy subjects: a comparison of egg albumin,
      casein, gelatin, soy protein, pea protein, and wheat gluten.
AB  - The influence of six dietary protein types (egg albumin, casein, gelatin, soy
      protein, pea protein, and wheat gluten) on satiety and food intake was
      investigated. Twelve healthy subjects ingested six protein-manipulated lunches
      (approximately 5.2 MJ, 22% of energy as protein) according to a within-subjects
      design. Test meals were controlled for energy, macronutrients, fiber, and
      palatability. Nearly 65% of total protein varied between sessions. After lunch,
      satiety was assessed for 8 h and energy and macronutrients intakes were measured
      for 24 h. Blood was collected for determination of postprandial plasma glucose
      and insulin responses. Results showed no effect of the type of protein on
      satiety, on 24-h energy or macronutrient intakes, or on postprandial plasma
      glucose and insulin concentrations. These findings differ in part from those
      obtained previously in humans, which suggested that proteins may be
      differentiated in terms of their satiating capacities. We conclude that varying
      the protein source in a mixed meal does not affect food behavior in healthy
      humans, probably because coingestion of carbohydrate and fat with protein buffers
      the kinetics of the physiologic mechanisms implicated in postprandial satiety
      after a protein load.

PMID- 9625095
TI  - Effects of flavonoids and vitamin C on oxidative DNA damage to human lymphocytes.
AB  - This study assessed the antioxidant potencies of several widespread dietary
      flavonoids across a range of concentrations and compared with vitamin C as a
      positive control. The antioxidant effects of pretreatment with flavonoids and
      vitamin C, at standardized concentrations (7.6, 23.2, 93, and 279.4 micromol/L),
      on oxygen radical-generated DNA damage from hydrogen peroxide (100 micromol/L) in
      human lymphocytes were examined by using the single-cell gel electrophoresis
      assay (comet assay). Pretreatment with all flavonoids and vitamin C produced dose
      dependent reductions in oxidative DNA damage. At a concentration of 279
      micromol/L, they were ranked in decreasing order of potency as follows: luteolin
      (9% of damage from unopposed hydrogen peroxide), myricetin (10%), quercetin
      (22%), kaempferol (32%), quercitrin (quercetin-3-L-rhamnoside) (45%), apigenin
      (59%), quercetin-3-glucoside (62%), rutin (quercetin-3-beta-D-rutinoside) (82%),
      and vitamin C (78%). The protective effect of vitamin C against DNA damage at
      this concentration was significantly less than that of all the flavonoids except
      apigenin, quercetin-3-glucoside, and rutin. The ranking was similar with
      estimated ED50 (concentration to produce 50% protection) values. The protective
      effect of quercetin and vitamin C at a concentration of 23.2 micromol/L was found
      to be additive (quercetin: 71% of maximal DNA damage from unopposed hydrogen
      peroxide; vitamin C: 83%; both in combination: 62%). These data suggest that the
      free flavonoids are more protective than the conjugated flavonoids (eg, quercetin
      compared with its conjugate quercetin-3-glucoside, P < 0.001). Data are also
      consistent with the hypothesis that antioxidant activity of free flavonoids is
      related to the number and position of hydroxyl groups.

PMID- 9625094
TI  - Whole-body protein kinetics in marasmus and kwashiorkor during acute infection.
AB  - Marasmus and kwashiorkor are clinically distinct manifestations of severe
      malnutrition. This study tested the hypothesis that rates of whole-body protein
      synthesis and breakdown are higher in marasmus than in kwashiorkor during acute
      infection. We measured whole-body protein kinetics using stable isotope tracers
      in eight children with marasmus and acute infection (pneumonia or malaria) to
      determine the rate of appearance of urea and leucine in plasma. Serum
      concentrations of total protein, albumin, and C-reactive protein were also
      measured. These findings were compared with those reported previously for 13
      children with kwashiorkor (including marasmic kwashiorkor) and acute infection
      who were studied with the same methods. HIV infection was present in 10 of 21
      children. Rates of protein breakdown and synthesis were higher in marasmus than
      in kwashiorkor (227 +/- 59 compared with 103 +/- 30 micromol leucine x kg(-1) x
      h(-1) and 216 +/- 60 compared with 97 +/- 30 micromol leucine x kg(-1) x h(-1), P
      < 0.001). The concentration of globulin (total protein minus albumin) was higher
      in marasmus than kwashiorkor (40 +/- 17 compared with 25 +/- 7 g/L, P < or =
      0.01), but C-reactive protein was not different (73 +/- 79 compared with 83 +/-
      89 mg/L). HIV infection and body composition did not explain the differences
      between marasmus and kwashiorkor. The accelerated rate of protein turnover in
      children with marasmus and acute infection requires further investigation.

PMID- 9625096
TI  - Copper absorption, excretion, and retention by young men consuming low dietary
      copper determined by using the stable isotope 65Cu.
AB  - A study was conducted in young men to evaluate the effect of a low-copper diet on
      copper absorption, excretion, and retention. Eleven young men were confined to a
      metabolic research unit for 90 d. The study was divided into three periods, with
      dietary copper as the only variable. Dietary copper intake was 0.66 mg/d for 24
      d, 0.38 mg/d for 42 d, and 2.49 mg/d for 24 d. The stable isotope 65Cu was fed to
      five of the subjects once during the first and last dietary period and twice,
      early and late, in the second period to determine copper absorption. 65Cu was
      infused into an arm vein of the other six subjects once during each dietary
      period to estimate excretion of endogenous copper. Total copper and 65Cu were
      determined by isotope dilution with thermal-ionization mass spectrometry.
      Fractional absorption was significantly higher during the low-copper period than
      in either period with higher dietary copper and excretion of the infused isotope
      was significantly lower in the low-copper period. Subjects were in negative
      balance early in the first two periods but achieved balance by the end of those
      periods. They retained copper during the highest dietary copper period (third
      period). The results suggest that endogenous copper excretion is a major point of
      regulation of the body's copper stores. Regulation of absorption and of
      endogenous excretion in response to dietary copper intake helps to protect
      against deficiency and toxicity. However, this regulation was not sufficient to
      maintain copper status at the lowest intake of dietary copper, 0.38 mg/d.

PMID- 9625097
TI  - Plasma lipoproteins as carriers of phylloquinone (vitamin K1) in humans.
AB  - The purpose of this study was to characterize the absorption and transport of
      phylloquinone (vitamin K1) by plasma lipoproteins. Twenty-six healthy subjects
      (11 men and 15 women) aged 20-78 y received phylloquinone in the amount of either
      1.43 or 50 microg/kg body wt orally with a fat-rich meal containing 1.0 g/kg body
      wt of fat, carbohydrate, and protein and 7.0 mg cholesterol/kg body wt. Blood was
      obtained at baseline (0 h) and 3, 6, 9, and 12 h after the meal for the
      measurement of plasma lipid and phylloquinone concentrations in plasma and
      lipoprotein subfractions. In both groups of subjects, triacylglycerol
      concentrations peaked after 3 h in plasma and in the triacylglycerol-rich
      lipoprotein fraction, composed of chylomicrons and VLDLs. Plasma phylloquinone
      concentrations peaked at 6 h. At baseline and during the postprandial phase, >
      53% of plasma phylloquinone was carried by the triacylglycerol-rich lipoprotein
      fraction. In 9 of the 11 subjects supplemented with 50 microg phylloquinone/kg,
      plasma lipoproteins were isolated by sequential ultracentrifugation. In these
      subjects the fraction of plasma phylloquinone carried by LDLs and by HDLs
      increased progressively from 3% and 4% at 3 h to 14% and 11% at 12 h,
      respectively. Our data indicate that whereas triacylglycerol-rich lipoproteins
      are the major carriers of phylloquinone, LDL and HDL may carry small fractions of
      this vitamin.

PMID- 9625098
TI  - Seasonal changes in plasma 25-hydroxyvitamin D concentrations of young American
      black and white women.
AB  - Seasonal changes in 25-hydroxyvitamin D concentrations were studied in 51 black
      and 39 white women aged 20-40 y from Boston. Individual measurements were made in
      February or March (February-March), June or July (June-July), October or November
      (October-November), and the following February or March (February-March). Samples
      from the four visits were analyzed in batches at the end of the study. Plasma 25
      hydroxyvitamin D was substantially lower in black than in white women at all the
      time points, including February-March when values were lowest (30.2 +/- 19.7
      nmol/L in black and 60.0 +/- 21.4 nmol/L in white women) and June-July when they
      were highest (41.0 +/- 16.4 nmol/L in black and 85.4 +/- 33.0 nmol/L in white
      women). Although both groups showed seasonal variation in 25-hydroxyvitamin D
      concentrations, the mean increase between February-March and June-July was
      smaller in black women (10.8 +/- 14.0 nmol/L compared with 25.4 +/- 29.8 nmol/L
      in white women, P = 0.006) and their overall amplitude of seasonal change was
      lower (P = 0.001). Concentrations of serum parathyroid hormone in February-March
      were significantly higher (P < 0.005) in black women (5.29 +/- 2.32 pmol/L) than
      in white women (4.08 +/- 1.41 pmol/L) and were significantly inversely correlated
      with 25-hydroxyvitamin D in blacks (r = -0.42, P = 0.002) but not in whites (r = 
      0.19, P = 0.246). Although it is well established that blacks have denser bones
      and lower fracture rates than whites, elevated parathyroid hormone concentrations
      resulting from low 25-hydroxyvitamin D concentrations may have negative skeletal
      consequences within black populations.

PMID- 9625099
TI  - Hyporetinolemia, illness symptoms, and acute phase protein response in pregnant
      women with and without night blindness.
AB  - We examined the association among elevations in acute phase proteins, reported
      illness, and hyporetinolemia in 234 pregnant Nepali women with (cases) and
      without (controls) night blindness. Serum alpha1-acid glycoprotein (AGP) and C
      reactive protein (CRP) were inversely associated with serum retinol
      concentrations. Elevations in the concentration of CRP in both cases and controls
      and of AGP in cases were associated with significant reductions (approximately
      0.2-0.3 micromol/L) in serum retinol. The risk of a low serum retinol
      concentration (< 0.7 micromol/L) with elevated AGP (> or = 1 g/L) and CRP (> or =
      5 mg/L) concentrations was significantly higher in cases (odds ratios = 8.6 and
      4.3, respectively) than in controls (odd ratios = 1.9 and 2.4, respectively). A 7
      d morbidity history indicated that cases were significantly more likely than
      controls to report symptoms of infections of the urinary, reproductive, and
      gastrointestinal tracts. Only a few of these symptoms (diarrhea, nausea, and
      vomiting) were significantly associated with low serum retinol concentrations.
      Illness in the previous week and elevated CRP or AGP concentrations were
      synergistically associated with lower serum retinol. For example, the reduction
      in serum retinol in women with diarrhea and elevated AGP was 0.54 micromol/L,
      compared with a reduction of 0.03 micromol/L in those with diarrhea only. AGP and
      CRP may provide useful information about the effect of reported illness on
      hyporetinolemia in pregnancy. Infection-related hyporetinolemia may predispose
      women to night blindness during pregnancy in Nepal.

PMID- 9625100
TI  - Effects of calcium supplementation and lactation on iron status.
AB  - Calcium has been shown to inhibit iron absorption. The consequences of chronic
      calcium supplementation on iron status are unclear, however. As part of a
      randomized calcium-supplementation trial in lactating and nonlactating women in
      the postpartum period, we determined whether long-term calcium supplementation
      and lactation status affected iron stores as measured by serum ferritin
      concentrations. Subjects (95 lactating and 92 nonlactating) were enrolled at
      approximately 6 mo postpartum and then randomly assigned to receive either 500 mg
      Ca as calcium carbonate or a placebo twice daily with meals for 6 mo. Lactating
      women weaned their infants approximately 2 mo after enrollment (ie, approximately
      8 mo postpartum). Calcium supplementation had no effect on serum ferritin
      concentrations. At the end of the study, geometric mean serum ferritin
      concentrations were 28.4 microg/L in the calcium-supplemented group and 27.5
      microg/L in the placebo group (P > 0.5). Lactation status was significantly
      related to serum ferritin concentrations. At baseline, serum ferritin
      concentrations were higher in lactating women than in nonlactating women (47.7
      compared with 31.5 microg/L, P < 0.001). In lactating women, serum ferritin
      concentrations decreased by a mean of 17 microg/L after weaning. By 12 mo
      postpartum, mean serum ferritin concentrations in women who were previously
      lactating were not significantly higher than those of nonlactating women (30.5
      compared with 25.5 microg/L). These findings provide reassurance that long-term
      calcium supplementation does not impair iron stores. Furthermore, lactation
      status should be considered when assessing iron nutriture of women and
      determinants of iron status in populations.

PMID- 9625101
TI  - Distribution of a stable isotope of chromium (53Cr) in serum, urine, and breast
      milk in lactating women.
AB  - To determine the fate and distribution of chromium during lactation, six
      lactating women (25-38 y old) were given three doses of the tracer 53Cr (7.55
      micromol/d, or 400 microg/d) on days 1, 2, and 3 of the study. Diet records,
      blood samples taken while subjects were fasting, and 24-h composite milk and
      urine samples were collected from day 0 to day 6. Fasting blood samples, morning
      milk samples, and 24-h urine samples were also collected on days 8, 10, 15, 30,
      60, and 90. 53Cr and natural and total chromium concentrations in biological
      fluids were measured with gas chromatography-mass spectrometry and total urinary
      chromium was measured with atomic-absorption spectrometry. 53Cr was detectable in
      serum 2 h after dosing and continued to be detected from day 30 to day 60.
      Changes in total serum chromium concentration in response to the oral dose
      suggested that chromium concentrations in blood were not tightly regulated. 53Cr
      was not detected in breast milk and no significant changes in natural chromium
      concentration in milk were observed in response to the oral doses, suggesting
      that breast-milk chromium concentrations are independent of intake. The estimated
      chromium intake of exclusively breast-fed infants was 2.5 nmol/d (0.13 microg/d),
      below the lower end of the range of estimated safe and adequate daily dietary
      intakes (10-40 microg/d) for infants 0-6 mo of age. The baseline chromium
      concentration in urine and the minimum 53Cr absorption in lactating women were
      comparable with values for nonpregnant, nonlactating subjects. Chromium losses in
      breast milk do not appear to be compensated for via increased absorption or
      decreased excretion.

PMID- 9625102
TI  - Energy expenditure of Chinese infants in Guangdong Province, south China,
      determined with use of the doubly labeled water method.
AB  - The doubly labeled water method was used to measure the energy expenditure of a
      group of 41, 4- or 6-mo-old infants with a cross-sectional design. The infants
      were divided into two groups according to whether they were breast-fed (11 at 4
      mo, 9 at 6 mo) or formula fed (11 at 4 mo, 10 at 6 mo). Anthropometric
      measurements were recorded at birth and at the beginning and end of the 8-d
      study. Anthropometric data, which were supported by the food intake and energy
      expenditure results, indicated that the infants were within the norms for
      European and American infants of the same age. Mean energy intakes of 352 kJ (84
      kcal) kg(-1) x d(-1) at 4 and 6 mo were lower than the FAO/WHO/UNU recommended
      value of 452 kJ (108 kcal) x kg(-1) x d(-1)) and Chinese recommendations of 502
      kJ (120 kcal) kg(-1) x d(-1). However, some authors believe that values of 398 kJ
      (95 kcal) kg(-1) x d(-1) at 4 mo and 356 kJ (85 kcal) kg(-1) x d(-1) at 6 mo are
      more appropriate. At 6 mo the infants' length-for-age and weight-for-age were at
      the National Center for Health Statistics 55th and 47th percentiles,
      respectively, whereas 58% were below the 50th percentile for weight-for-length.
      We conclude that at 4 mo infants receive sufficient energy for their
      requirements. However, at 6 mo energy requirements might well be greater than the
      revised recommendations, when infants are being weaned to alternative foods and
      are more prone to the influence of diet on their growth and development.

PMID- 9625103
TI  - Medium-chain compared with long-chain triacylglycerol emulsions enhance
      macrophage response and increase mucosal mass in parenterally fed rats.
AB  - We tested whether infusion of medium-chain triacylglycerols (MCTs) during total
      parenteral nutrition (TPN) enhanced macrophage response and reduced intestinal
      atrophy compared with long-chain triacylglycerols (LCTs). Male Sprague-Dawley
      rats (230-240 g) were maintained with TPN providing 16% or 48% of nonprotein
      energy from MCTs plus LCTs or LCTs alone or 100% of nonprotein energy from
      dextrose for 6 or 12 d. Body weight gain was not significantly different among
      groups. Serum concentrations of beta-hydroxybutyrate were greater with MCTs plus
      LCTs than with LCTs alone after 6 d (P < 0.05, main effect). Triacylglycerol
      concentrations in liver were greater with LCTs than with MCTs plus LCTs after 6
      or 12 d (P < 0.05, main effect). MCTs plus LCTs increased by 50% the percentage
      (P < 0.0005) and number of splenic macrophages compared with LCTs alone in
      conjunction with decreased triacylglycerol concentrations in spleen after 6 d (P
      < 0.05, main effect). In vitro tumor necrosis factor alpha secretion by splenic
      or circulating macrophages in response to lipopolysaccharide was increased by
      MCTs plus LCTs compared with LCTs alone, twofold after 6 and sevenfold after 12 d
      (P < 0.05, main effect). Jejunal mucosal mass was 30% greater with MCTs plus LCTs
      than with LCTs alone after 6 or 12 d (P < 0.01); villus height was also
      significantly greater after 6 d (main effect). The incidence of bacterial
      translocation to the mesenteric lymph nodes was not significantly different among
      groups. Compared with LCTs, MCTs enhanced macrophage response and decreased
      intestinal atrophy.

PMID- 9625104
TI  - Biochemical effects of calcium supplementation in postmenopausal women: influence
      of dietary calcium intake.
AB  - We studied the biochemical effects of calcium supplementation during a 2-mo
      course in postmenopausal women (x +/- SD: 64 +/- 5 y of age and 14.5 +/- 6.7 y
      since menopause). The effects on calcium homeostasis and bone remodeling were
      assessed after 1 and 2 mo of daily administration of either calcium carbonate
      (1200 mg elemental Ca/d, n = 60) or a placebo (n = 56). The daily dietary calcium
      intake assessed before the beginning of calcium supplementation was 786 mg/d. We
      found a significant inverse relation between baseline intact parathyroid hormone
      (iPTH) and dietary calcium intake before supplementation (r = -0.48, P = 0.0002).
      A significant increase in urinary excretion of pyridinoline was observed when the
      dietary calcium intake was lower than the median value. Calcium supplementation
      resulted in a significant increase in 24-h urinary calcium (39%, P < 0.02) and a
      significant reduction of bone alkaline phosphatase at 2 mo and of all bone
      resorption markers (hydroxyproline, pyridinoline, and deoxypyridinoline) at I and
      2 mo without significant changes in 44-68 PTH fragments or iPTH concentrations.
      When the dietary calcium intake was low (mean +/- SD: 576 +/- 142 mg/d), calcium
      supplementation was responsible for a greater increase in urinary calcium
      excretion and a greater decrease in markers of bone turnover. The greatest
      variations were observed for deoxypyridinoline at 1 and 2 mo (-18.5%, P < 0.05)
      and for pyridinoline at 1 mo (-16.3%, P < 0.01). Two months of calcium
      supplementation in postmenopausal women was efficient in reducing markers of bone
      turnover, with a greater effect in women with a low dietary calcium intake.

PMID- 9625105
TI  - Intermittent oral administration of potassium iodide solution for the correction
      of iodine deficiency.
AB  - Iodized salt and iodized oil are the main methods used to prevent iodine
      deficiency, but sometimes alternative approaches are needed. We tested the
      efficacy of various regimens for the intermittent administration of potassium
      iodide in Hwedza, Zimbabwe, an area of known severe iodine deficiency. We divided
      304 schoolchildren aged 7-13 y into five equal groups that received iodine as a
      10% solution of potassium iodide as follows: 8.7 mg every 2 wk (group A), 29.7 mg
      every month (group B), 148.2 mg every 3 mo (group C), 382 mg every 6 mo (group
      D), or 993 mg once (group E). The follow-up period was 13 mo. No adverse effects
      were encountered with any of these doses. After 6 mo, the median blood spot
      thyroglobulin concentration had decreased in all groups and had normalized in
      groups A and B to values found in iodine-sufficient populations. The number of
      children with elevated thyroid-stimulating hormone concentrations decreased in
      groups A-C, but the changes were not significant. Urine iodine concentration
      generally remained low in all groups but increased in group A. After 13 mo, mean
      thyroid volume measured by ultrasound had decreased in groups A and B to values
      comparable with those in iodine-sufficient areas, and was unchanged in the other
      groups. We conclude that oral potassium iodide is effective for the prophylaxis
      of iodine deficiency if given as a dose of 30 mg I monthly or 8 mg biweekly.

PMID- 9625106
TI  - Gender differences--do they really count?

PMID- 9625107
TI  - Complementary medicine use by patients with inflammatory bowel disease.

PMID- 9625108
TI  - Doctor-patient relationship: perspectives, needs, and communication.

PMID- 9625109
TI  - Cholestatic liver diseases in adults.
AB  - Cholestatic liver diseases are a diverse group of disorders that are recognized
      by either increases in laboratory studies or the appearance of jaundice, fatigue,
      pruritus, and/or complications of cirrhosis. The etiologies for most forms of
      these diseases are unknown. In this paper, diagnostic and therapeutic strategies
      are reviewed for select forms of cholestatic disorders and for the management of
      shared complications of cholestatic illness.

PMID- 9625110
TI  - Intestinal tuberculosis: return of an old disease.
AB  - OBJECTIVE: Tuberculosis (TB) can no longer be considered a rare disease in the
      United States due, in part, to the AIDS epidemic. Because the signs and symptoms
      of intestinal TB are nonspecific, a high index of suspicion must be maintained to
      ensure a timely diagnosis. The aim of this article is to review the history,
      epidemiology, pathophysiology, and treatment of TB. METHODS: This review is based
      on an examination of the world literature. RESULTS: In only 20% of TB patients is
      there associated active pulmonary TB. Areas most commonly affected are the
      jejunoileum and ileocecum, which comprise >75% of gastrointestinal TB sites.
      Diagnosis requires colonoscopy with multiple biopsies at the ulcer margins and
      tissue sent for routine histology, smear, and culture. If intestinal TB is
      suspected, empiric treatment is warranted despite negative histology, smear, and
      culture results. Treatment is medical, and all patients should receive a full
      course of antituberculous chemotherapy. Exploratory laparotomy is necessary if
      the diagnosis is in doubt, in cases in which there is concern about a neoplasm,
      or for complications that include perforation, obstruction, hemorrhage, or
      fistulization. CONCLUSIONS: This review draws attention to the resurgence of
      tuberculosis in the United States. An increased awareness of intestinal
      tuberculosis, coupled with knowledge of the pathophysiology, diagnostic methods,
      and treatment should increase the number of cases diagnosed, thus improving the
      outcome for patients with this disease.

PMID- 9625111
TI  - Complementary medicine use by patients with inflammatory bowel disease.
AB  - OBJECTIVE: The purpose of this study was to establish the degree and determinants
      of the use of complementary therapies by patients with inflammatory bowel disease
      (IBD) and their reasons for seeking them. METHODS: The first phase was a cross
      sectional survey of 134 patients with IBD (98 with Crohn's disease, 34 with
      ulcerative colitis, and two indeterminate) using a mailed, structured
      questionnaire (response rate 70%). Determinants of complementary medicine use
      were examined using logistic regression. The second phase was an in-depth
      exploration using personal interviews of the beliefs and perceptions of 14
      complementary medicine users about the management of their disease. Analysis was
      performed using standard qualitative techniques and the identification of
      important, patient-identified themes about the management of IBD. RESULTS:
      Complementary therapies had been used by 51% of patients in the previous 2 yr.
      Current use was reported by 33%, of whom one-half were using it for their IBD.
      Vitamins and herbal products were the most commonly reported therapies. In
      multivariate analysis, duration of disease > 10 yr and a history of
      hospitalization were independent predictors of complementary medicine use. The
      side effects and lack of effectiveness of standard therapies were the most
      commonly cited reasons for seeking complementary medicine. Sixty-two percent had
      told their doctor about their use of complementary medicine. CONCLUSION:
      Complementary medicine use is common in patients with IBD, especially among those
      with a longer duration of disease or a history of hospitalization.

PMID- 9625112
TI  - Changing trends in esophageal cancer: a 15-year experience in a single center.
AB  - OBJECTIVE: Esophageal adenocarcinoma is increasing in white men. We sought to
      identify trends in esophageal cancer in different patient groups in our region.
      METHODS: We reviewed the records of all patients with esophageal cancer seen at
      two hospitals in Columbia, SC between 1981 and 1995. Patients were divided into
      three cohorts (1981-1985, 1986-1990, and 1991-1995). Demographic data,
      histological type, tumor stage, grade, and survival were recorded. RESULTS:
      Histology was available in 371 of 386 patients (cohort 1, 113 patients; cohort 2,
      144; and cohort 3, 114). Adenocarcinoma accounted for 24%, 27%, and 49% of
      esophageal cancer in white men in cohorts 1, 2, and 3, respectively (p = 0.03).
      Corresponding figures for African-Americans were 10%, 7%, and 3% (p = 0.22).
      Women comprised 8%, 14%, and 22% of patients with squamous carcinoma in the three
      cohorts (p = 0.03). Median survival for esophageal cancer was 6.0, 6.8, and 10.4
      mo in cohorts 1, 2, and 3 (p = 0.0002). CONCLUSION: Adenocarcinoma is increasing
      in whites. Squamous carcinoma remains the predominant type in this region, seen
      mainly in African-Americans. Esophageal squamous carcinoma is increasing in
      women. The mean age at diagnosis of squamous carcinoma has decreased in whites.
      There is a trend toward improved survival in patients with esophageal cancer.

PMID- 9625113
TI  - Esophageal manometry: a comparison of findings in younger and older patients.
AB  - OBJECTIVE: We sought to determine the utility of esophageal manometry in an older
      patient population. METHODS: Consecutively performed manometry studies (470) were
      reviewed and two groups were chosen for the study, those > or = 75 yr of age (66
      patients) and those < or = 50 years (122 patients). Symptoms, manometric findings
      (lower esophageal sphincter [LES], esophageal body, upper esophageal sphincter
      [UES]) and diagnoses were compared between the groups. RESULTS: Dysphagia was
      more common (60.6% vs 25.4%), and chest pain was less common (17.9 vs 26.2%) in
      older patients. In the entire group, there were no differences in LES parameters.
      Older patients with achalasia had lower LES residual pressures after deglutition
      (2.7 vs 12.0 mm Hg), but had similar resting pressures (31.4 vs 35.2 mm Hg)
      compared with younger achalasia patients. Duration and amplitude of peristalsis
      were similar in both groups, whereas peristaltic sequences were more likely to be
      simultaneous in the older group (15% vs 4%). The UES had a lower resting pressure
      in the older patients (49.6 vs 77.6 mm Hg) and a higher residual pressure (2.0 vs
      -2.7 mm Hg). The older patients were less likely to have normal motility (30.3%
      vs 44.3%) and were more likely to have achalasia (15.2% vs 4.1%) or diffuse
      esophageal spasm (16.6% vs 5.0%). When only patients with dysphagia were
      analyzed, achalasia was still more likely in the older group (20.0% vs 12.9%).
      CONCLUSION: When older patients present with dysphagia, esophageal manometry
      frequently yields a diagnosis to help explain their symptoms.

PMID- 9625114
TI  - Complete elimination of reflux symptoms does not guarantee normalization of
      intraesophageal acid reflux in patients with Barrett's esophagus.
AB  - OBJECTIVE: Normalization of intraesophageal acid exposure is increasingly
      recognized as a desired goal in the management of Barrett's esophagus. In this
      prospective trial, we studied patients with Barrett's esophagus by 24-h
      intraesophageal pH monitoring after having completely eliminated their reflux
      symptoms with lansoprazole, to determine whether they had achieved normalization
      of intraesophageal pH. METHODS: Thirty patients with Barrett's esophagus, all of
      whom had presented with reflux symptoms, were treated with lansoprazole (15-30
      mg/day) until they were asymptomatic. Twenty-four-hour ambulatory pH monitoring
      was performed while they were receiving lansoprazole and were asymptomatic.
      RESULTS: Twelve patients (40%) showed persistent bipositional, pathologic acid
      reflux while on therapy, with a mean DeMeester score of 52.8 (95% CI: 33.8-71.8);
      the remaining 18 (60%) exhibited normalization of intraesophageal acid exposure
      with a score of 4.4 (95% CI: 2.3-6.6,p < 0.001). This inadequate control of
      intraesophageal pH is most likely due to incomplete gastric acid suppression
      induced by the drug and is associated with a variable acid (distal > proximal)
      exposure within the esophagus. The two groups were not different in regard to
      their symptom frequency and severity before therapy, amount of lansoprazole
      dosage required to eliminate symptoms, length of Barrett's metaplasia, presence
      of hiatal hernia, lower esophageal sphincter resting tone and length, or
      esophageal peristaltic function. CONCLUSION: Complete symptom eradication with
      lansoprazole (15-30 mg daily) in patients with Barrett's esophagus does not
      guarantee normalization of intraesophageal pH profile. If the goal of therapy in
      such patients is to achieve complete intraesophageal acid suppression, 24-h
      ambulatory esophageal pH monitoring should be performed to titrate therapy.

PMID- 9625115
TI  - A prospective, controlled study of Helicobacter pylori seroprevalence in coronary
      artery disease.
AB  - OBJECTIVE: Recent studies have suggested that chronic infections may be a risk
      factor for coronary artery disease. The aim of this study was to determine
      whether Helicobacter pylori (H. pylori) infection was an independent risk factor
      for coronary artery disease. METHODS: A total of 179 patients undergoing coronary
      angiography for suspected coronary artery disease were prospectively studied.
      Angiograms were read by experienced invasive cardiologists blinded to the results
      of H. pylori serology, which was determined by a validated multiwell ELISA assay.
      RESULTS: A total of 121 patients (68%) had evidence of coronary artery disease,
      whereas 58 patients (32%) had normal coronary angiograms. Of the 121 patients
      with coronary artery disease, 29 had single vessel disease, 39 had double vessel
      disease, and 53 had triple vessel disease, respectively. There was no significant
      difference in seroprevalence of H. pylori infection in patients with and without
      coronary artery disease (p = 0.63). The odds ratio (after adjustment for other
      known risk factors) for coronary artery disease in H. pylori-infected subjects
      was 0.45 (95% CI = 0.15, 1.37; p = 0.107). In patients with coronary artery
      disease, H. pylori infection did not increase the likelihood of severe disease
      (odds ratio for triple vessel disease = 0.53; 95% CI 0.18, 1.60; p = 0.201).
      CONCLUSION: H. pylori infection rates are similar in patients with normal and
      abnormal coronary arteries, and infection with H. pylori is not an independent
      risk factor for coronary artery disease. In patients who have coronary artery
      disease, H. pylori infection is not a risk factor for more severe disease. These
      data argue against a causal role for H. pylori in the pathogenesis of coronary
      artery disease.

PMID- 9625116
TI  - Clinical aspects of upper gastrointestinal bleeding associated with the use of
      nonsteroidal antiinflammatory drugs.
AB  - OBJECTIVE: The aim of this study was to compare the clinical features of major
      upper gastrointestinal bleeding among patients exposed to nonsteroidal
      antiinflammatory drugs (NSAID) and those not taking these drugs. METHODS: Using
      data from a multicenter international case-control study designed to evaluate the
      role of drugs in the etiology of major upper gastrointestinal bleeding (UGIB),
      patients with a confirmed first episode of major UGIB were divided into two
      groups: those exposed to NSAIDs during the week before the onset of bleeding, and
      those not exposed. The groups were compared according to age and sex, clinical
      appearance and site of the bleeding, preceding symptoms, and requirement for
      transfusion and acute surgery. RESULTS: The median age was significantly higher
      and the proportion of women was slightly higher among the NSAID users. There was
      no significant difference between users and nonusers according to the clinical
      presentation, the site of the bleeding, or the frequency of preceding symptoms.
      Forty percent in each group had no symptoms before the onset of bleeding.
      Slightly more NSAID users received blood transfusions, although the same median
      amount of blood per transfusion was given in both groups. There was no difference
      in the frequency of surgical intervention. CONCLUSIONS: There are no important
      differences in the clinical presentation of major UGIB according to whether or
      not an individual is an NSAID user. An important finding is the frequent absence
      of preceding symptoms in patients with major UGIB, regardless of NSAID use.

PMID- 9625117
TI  - Analysis of risk factors for chronic hepatic encephalopathy: the role of
      Helicobacter pylori infection.
AB  - OBJECTIVE: Elevated blood ammonia is an important pathogenic factor of hepatic
      encephalopathy. Although colonic bacteria are considered the main source of
      ammonia, the stomach in subjects with urease-producing Helicobacter pylori (H.
      pylori) is an alternative site. The objective of this study was to determine
      whether H. pylori is associated with this complication. METHODS: After assessing
      liver function and portal hypertension, 55 cirrhotics were evaluated for
      encephalopathy and H. pylori infection. Response to 2 weeks of amoxicillin (2
      g/day) and omeprazole (40 mg/day) was then assessed in 17 (13 H. pylori-positive,
      four H. pylori-negative) encephalopathic subjects. RESULTS: H. pylori infection
      was more common (67 % vs 33%, p = 0.004) among encephalopathic patients.
      Additional factors associated with encephalopathy included older age (60.1 +/-
      1.5 vs 49.8 +/- 2.4 yr, p = 0.001), lower albumin (3.17 +/- 0.08 vs 3.69 +/- 0.12
      g/dl, p = 0.001), higher total bilirubin (2.24 +/- 0.20 vs 1.53 +/- 0.23 mg/dl, p
      = 0.034), greater ascites score (0.8 +/- 0.1 vs 0.3 +/- 0.1, p = 0.01), greater
      diuretic score (1.1 +/- 0.1 vs 0.3 +/- 0.1, p = 0.002), and greater modified
      Child score (6.7 +/- 0.3 vs 5.1 +/- 0.3, p = 0.001). When adjusted for severity
      of cirrhosis and age, H. pylori continued to demonstrate a statistical
      association (p = 0.039). After anti-H. pylori therapy, symptomatology in infected
      encephalopathic patients appeared to improve, whereas noninfected subjects were
      unaffected. CONCLUSION: In cirrhotic patients, H. pylori infection is associated
      with hepatic encephalopathy, especially in younger patients with decompensated
      liver disease.

PMID- 9625118
TI  - Treatment of gastric MALT lymphoma by Helicobacter pylori eradication: a study
      controlled by endoscopic ultrasonography.
AB  - OBJECTIVE: Previous studies have demonstrated a link between Helicobacter pylori
      infection and low grade B-cell gastric MALT lymphoma. The aim of this study was
      to evaluate the effect of Helicobacter pylori eradication in 17 patients with low
      grade B-cell gastric MALT lymphoma stage EI. METHODS: For disease staging EUS and
      CT scan were systematically performed. Eight patients were excluded from the
      present series because stage EII disease was diagnosed. To demonstrate B-cell
      monoclonality, immunohistochemistry and polymerase chain reaction were used. H.
      pylori eradication was performed with triple therapy. RESULTS: H. pylori was
      eradicated in all patients after first (n = 15) or second line (n = 2) treatment.
      Histologic regression of lymphoma was observed in all patients after a median
      period of 2 mo. Disappearance of monoclonality according to polymerase chain
      reaction took significantly longer (7 mo). At the end of the study, four of 16
      patients still exhibited persistent monoclonal bands. Relapse of lymphoma
      occurred in two patients associated with H. pylori reinfection/recrudescence.
      CONCLUSION: Eradication of H. pylori seems to be an effective therapy in patients
      with stage EI gastric MALT lymphoma, although long-term results are still
      uncertain. Endoscopic ultrasonography is useful for a more accurate staging of
      the disease. The clinical significance of detecting monoclonality by polymerase
      chain reaction remains to be determined.

PMID- 9625119
TI  - Weekend therapy for the treatment of Helicobacter pylori infection.
AB  - OBJECTIVES: The aim of the present study was to evaluate the efficacy and the
      safety of a short-term regimen (weekend therapy) in the cure of Helicobacter
      pylori infection and to analyze the factors that may influence the success of the
      treatment. METHODS: Seventy-one patients with gastric colonization by a
      tinidazole sensitive H. pylori strain (34 duodenal ulcer and 37 nonulcer
      dyspepsia) received omeprazole 40 mg o.m. for 7 days (from Monday to Sunday) and
      bismuth 240 mg q.i.d. + amoxicillin 1000 mg/q.i.d. + tinidazole 500 mg q.i.d. for
      only 2 days (Saturday and Sunday). Endoscopy, histology, culture, urease test,
      and susceptibility studies were done at entry and 30 days after treatment.
      RESULTS: Successful eradication was obtained in 84% of patients. The percentage
      of eradication was higher in duodenal ulcer patients (94%) than in those with
      nonulcer dyspepsia (74%; p < 0.05), and in patients who received the treatment
      during hot weather (94%) than in those who received the treatment during cold
      weather (74%; p < 0.05). Side-effects were induced by the treatment in 17% of
      patients, and these were all not severe, self-limiting, short-lasting, and did
      not require specific treatment. CONCLUSIONS: These data suggested that weekend
      therapy with high doses of drugs represents an effective, safe, and inexpensive
      therapeutic approach for the treatment of H. pylori infection, particularly in
      patients with duodenal ulcer. Furthermore, they also confirm the relevant role
      that short-term treatments may play in the therapeutic approach to H. pylori
      infection, and highlight some important aspects influencing short-term schedules.

PMID- 9625120
TI  - A cost analysis of a Helicobacter pylori eradication strategy in a large health
      maintenance organization.
AB  - OBJECTIVES: We sought to describe the effect of a Helicobacter pylori eradication
      strategy on health care costs among a cohort of health maintenance organization
      (HMO) members with peptic ulcer disease (PUD). METHODS: Patients were identified
      from an outpatient diagnosis database and verified at chart review to have new
      onset PUD by upper endoscopy or upper gastrointestinal radiographic series.
      Health plan registration and accounting databases were used to track costs over
      12 months after initial diagnosis. Costs were analyzed separately for an initial
      2-month interval and a 10-month follow-up period. Inpatient and pharmacy costs
      are those directly attributable to PUD (either a PUD-related discharge diagnosis
      or an antiulcer medication prescription). Outpatient costs are total costs. All
      cost differences were adjusted for age and gender. RESULTS: Twenty-seven of 93
      patients meeting selection criteria received H. pylori treatment. During the 2
      month treatment window, adjusted PUD-related inpatient costs were higher for the
      H. pylori treated group (difference, $234.00/person), whereas total outpatient
      costs and PUD-related pharmacy costs were similar. During the 10-month follow-up
      period, PUD-related inpatient and pharmacy adjusted costs were similar, but
      adjusted outpatient costs in the H. pylori treated group were lower than in the
      untreated group (difference, $508.00/person). Total adjusted follow-up period
      costs were $555.00/person less in the H. pylori treated group (p = 0.05). Total
      12-month costs in the H. pylori treated group were $285.00/per person less than
      in untreated patients, (p > 0.2); 30% of H. pylori treated patients were still
      receiving antisecretory therapy 1 yr after diagnosis, compared to 41.9% of
      untreated patients. CONCLUSIONS: H. pylori treatment is associated with a
      decreased cost of follow-up care for patients with PUD, primarily due to
      decreased outpatient utilization.

PMID- 9625121
TI  - The association between antral G and D cells and mucosal inflammation, atrophy,
      and Helicobacter pylori infection in subjects with normal mucosa, chronic
      gastritis, and duodenal ulcer.
AB  - OBJECTIVE: The aim of this study was to clarify the mechanism of inappropriate
      hypergastrinemia in Helicobacter pylori (H. pylori)-infected subjects. METHODS:
      We measured fasting serum gastrin (SG) concentrations, and investigated
      immunohistochemically G and D cell numbers in 47 subjects with normal mucosa, 24
      subjects with chronic gastritis, and 24 subjects with duodenal ulcer (DU). The
      degree of inflammation and atrophy were classified into four categories based on
      criteria established in the Sydney System: none, mild, moderate, and severe.
      Avidin-biotin complex methods were used to identify G and D cells, which were
      counted per unit square (0.25 mm2) in five random fields from each of two well
      oriented antral and fundic biopsies. SG concentrations were measured by
      radioimmunoassay. RESULTS: The G cell number was not significantly different
      between 24 subjects with H. pylori-associated gastritis and those with DU.
      However, the number of antral D cells was significantly lower and the G/D cell
      ratio was significantly higher in subjects with DU than in those with H. pylori
      associated gastritis (p < 0.01), although the degree of inflammation and atrophy
      in the antrum and H. pylori status were similar between the two groups. The mean
      fasting SG concentration was higher in subjects with DU than in those with H.
      pylori-associated gastritis, but the difference was not statistically
      significant. CONCLUSIONS: Our results demonstrate that a marked decrease in
      antral D cell number with a high G/D cell ratio may contribute to
      hypergastrinemia and the pathogenesis of DU.

PMID- 9625122
TI  - Effects of alendronate on gastric and duodenal mucosa.
AB  - OBJECTIVES: This single-center, double-blind, randomized study assessed the
      effect of alendronate 5 and 10 mg on the gastroduodenal mucosa. METHODS: Overall,
      95 postmenopausal women without a recent history of major upper gastrointestinal
      (GI) disease and not taking gastric-irritant drugs, were screened with an upper
      GI endoscopy. Fourteen women (15% of the total) were found to have baseline
      endoscopic gastric and/or duodenal abnormalities, including mucosal hemorrhages
      (n = 4), erosions (n = 11), and ulcers (n = 3). Two additional women had baseline
      esophageal abnormalities. Thus, 79 postmenopausal women (mean age 51 yr, range 41
      64 yr), free of esophageal, gastric and/or duodenal erosions or ulcer, were
      enrolled. Subjects received placebo, alendronate 5 mg/day or 10 mg/day, or
      aspirin 650 mg q.i.d. for 14 days. Endoscopy was repeated on Day 8 and on Day 15.
      Gastric and duodenal mucosae were graded separately using a 5-point scale for
      erosive mucosal injury. RESULTS: The proportions of subjects with a gastric or
      duodenal erosion score > or = 2 (presence of at least one mucosal erosion) on
      either Day 8 or 15 were four of 22 (18.2%) in the placebo group; four of 22
      (18.2%) in the alendronate 5 mg group; five of 21 (23.8%) in the alendronate 10
      mg group; and 14 of 14 (100.0%) in the aspirin group. Thirty-five of 76 (46%)
      subjects were H. pylori-positive (Pyloritek test), and were equally distributed
      across treatment groups. CONCLUSIONS: Alendronate 5 and 10 mg/day for 2 wk was
      associated with a lower incidence of gastric erosions than aspirin. The incidence
      of gastric erosions in the alendronate groups did not differ significantly from
      the placebo group. In this study, unlike aspirin, alendronate did not induce
      gastric erosions.

PMID- 9625123
TI  - Synchronous gastric tumors associated with esophageal cancer: a retrospective
      study of twenty-four patients.
AB  - OBJECTIVES: Synchronous gastric tumors (including benign and secondary tumors)
      associated with esophageal cancer present diagnostic and therapeutic issues. We
      investigated this synchronous association, and retrospectively determined the
      frequency of the gastric tumors and the clinical characteristics. METHODS: In a
      series of 208 patients with esophageal cancer, we investigated the synchronous
      gastric tumors, as well as the frequency of association, clinicopathological
      characteristics, diagnosis, treatment, and the clinical outcome after surgery.
      RESULTS: Twenty-eight gastric tumors were found in 24 patients. Adenocarcinoma
      was most frequent. Most of these tumors were located at the upper or middle third
      of the stomach. Eight gastric tumors in six patients could not be detected
      preoperatively. Six of these tumors including a gastric remnant cancer were
      detected in the resected stomach, and two leiomyomas were detected during the
      operation. In one patient in which an endoscope could not pass through the
      esophagus, a leiomyoma was detected in the resected stomach. For the gastric
      cancers, total gastrectomy or proximal gastrectomy with lymph node dissections
      was performed. For the benign tumors, partial resection of the stomach was
      performed, and endoscopic resection was performed preoperatively for an adenoma.
      In both the postoperative hospital mortality rate and the survival rate after
      surgery, there were no significant differences between the patients with and
      without gastric tumors. CONCLUSIONS: Synchronous gastric tumors associated with
      esophageal cancer are not rare. When an endoscope cannot pass through the
      esophagus before surgery, other techniques must be performed to explore the
      stomach. For these patients, surgical treatment should be adapted positively.

PMID- 9625124
TI  - Nocturnal recovery of gastric acid secretion with twice-daily dosing of proton
      pump inhibitors.
AB  - OBJECTIVES: It is our experience that many patients treated with proton pump
      inhibitors (PPI) b.i.d. recover acid secretion during the night. Our aim was to
      assess the efficacy of omeprazole and lansoprazole b.i.d. on nocturnal gastric
      acidity. METHODS: Three groups were studied with intragastric pH monitoring.
      Group 1 consisted of 17 patients with gastroesophageal reflux disease (GERD)
      taking omeprazole 20 mg b.i.d. Group 2 was 16 male volunteers taking omeprazole
      20 mg b.i.d. and Group 3 comprised 12 volunteers taking lansoprazole 30 mg b.i.d.
      RESULTS: The percentages of time that subjects had pH < 4 were lower during
      supine than upright periods in Groups 1 and 3 (P < 0.01). Recovery of nocturnal
      acid secretion lasting > 1 h, termed acid breakthrough, occurred in three-fourths
      of all individuals within 12 h from intake of the evening dose of PPI. Median
      time to acid breakthrough for the whole group was 7.5 h. CONCLUSION: Nocturnal
      acid breakthrough occurs in a majority of patients and normal volunteers taking
      PPI b.i.d.

PMID- 9625125
TI  - Appendicitis: the impact of computed tomography imaging on negative appendectomy
      and perforation rates.
AB  - OBJECTIVES: The purposes of this study were to investigate the use of computed
      tomography (CT) imaging in patients with suspected acute appendicitis and to
      evaluate the impact of CT on negative appendectomy and perforation rates. In
      patients clinically diagnosed of acute appendicitis the reported overall negative
      appendectomy rate is about 15-20%; 10% in men and 25-45% in women of childbearing
      age. This is associated with a perforation rate of 21-23%. METHODS: This is a
      retrospective analysis of 146 consecutive patients presenting with clinical
      symptoms suspicious of appendicitis over a 2-yr period in whom CT examinations
      were performed before therapy was instituted. The overall negative appendectomy
      and perforation rates were calculated for the entire group, as well as for the 54
      women aged 15-50 yr in the childbearing cohort. RESULTS: The negative
      appendectomy rate was 4% in 122 patients operated on and the perforation rate was
      22%. Among 36 women 15-50 yr of age operated on, the negative appendectomy rate
      was 8.3% and the perforation rate was 19%. Surgery was avoided in 24 patients, 18
      of whom were women of childbearing age. CONCLUSIONS: The judicious use of CT
      imaging in patients with equivocal clinical presentation suspected of having
      appendicitis led to a significant improvement in the preoperative diagnosis. It
      resulted in a substantial decrease in the negative appendectomy rate compared to
      previously published reports, without incurring an increase in the perforation
      rate.

PMID- 9625126
TI  - Serious gastrointestinal pathology found in patients with serum ferritin values <
      or = 50 ng/ml.
AB  - OBJECTIVE: Our aim was to evaluate the gastrointestinal tract in patients with
      serum ferritin values < or = 50 ng/ml for the presence of serious
      gastrointestinal pathology, including neoplasia and acid peptic disease. METHODS:
      In this prospective observational study, patients with serum ferritin values < or
      = 50 ng/ml who did not have an obvious cause of iron deficiency underwent
      colonoscopy and/or esophagogastroduodenoscopy. RESULTS: Between October 1, 1994,
      and February 29, 1996, 725 of 3015 patients who had serum ferritin determinations
      were found to have values < or = 50 ng/ml. To date, 143 patients have been fully
      evaluated and 77 were found to have serious gastrointestinal pathology including
      acid peptic disease (N = 46), cancer (N = 15), and large adenomas (N = 6). Colon
      cancer was discovered in five asymptomatic patients. The prevalences of serious
      gastrointestinal pathology did not differ between patients with serum ferritin
      values < or = 20 ng/ml and those with values between 21-50 ng/ml (63% vs 48%, p =
      0.07). However, multivariate analysis showed that the presence of upper or lower
      gastrointestinal symptoms and serum ferritin value < or = 20 ng/ml is predictive
      of finding serious pathology (p = 0.0002 for the whole model), with odds ratios
      of 3.8 (95% confidence interval of 1.84-7.70) for presence of gastrointestinal
      symptoms and 2.2 (95% confidence interval of 1.09-4.57) for serum ferritin value
      < or = 20 ng/ml. CONCLUSIONS: Endoscopic examination is warranted in patients
      with serum ferritin values < or = 50 ng/ml to detect serious gastrointestinal
      pathology, present in 54% of such patients.

PMID- 9625127
TI  - Autoimmune hepatitis overlapping with primary sclerosing cholangitis in five
      cases.
AB  - OBJECTIVE: We report five cases (four male; median age 20 yr, range 14-38 yr) of
      an autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome. The
      patients presented with jaundice, elevated serum aminotransferase and alkaline
      phosphatase activities, hyperglobulinemia with high immunoglobulin G (IgG)
      levels, circulating antinuclear and/or smooth muscle autoantibodies (> or =
      1:40), and moderate to severe interface hepatitis on liver biopsy (with biliary
      features in four). METHODS: All five fulfilled criteria for diagnosis of
      "definite" autoimmune hepatitis and showed marked responses to prednisolone and
      azathioprine therapy, with relapses occurring during reduction or withdrawal of
      treatment. Cholangiographic features of primary sclerosing cholangitis were found
      in three patients at presentation and after intervals of 7 and 14 yr in the other
      two. Only two had evidence of inflammatory bowel disease. Diagnostic criteria for
      identifying those patients who may benefit from immunosuppressive therapy were
      reviewed. RESULTS: Review of the literature revealed only 11 similar cases that
      were sufficiently well described for comparison. However, in contrast to these
      and the present cases, preliminary data from other studies have suggested a
      marked association with ulcerative colitis and a poor response to
      immunosuppressive therapy. CONCLUSIONS: It is recommended that the possibility of
      an autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome
      responsive to immunosuppressive therapy should be considered in any patient
      presenting with a hepatitic illness with hyperglobulinemia, antinuclear or smooth
      muscle autoantibodies, and biliary changes on liver biopsy. Cholangiography
      should be considered in such patients.

PMID- 9625128
TI  - Hepatitis C virus and depression in drug users.
AB  - OBJECTIVES: Clinical case studies have implicated depression as a possible side
      effect of interferon treatment for the Hepatitis C virus (HCV). However, because
      these studies generally did not include a pretreatment assessment of depression,
      it cannot be definitively stated whether depression is a side-effect of
      interferon treatment, a syndrome coexisting with HCV, or a common characteristic
      of individuals who are vulnerable to HCV infection. To gather more information
      about this issue, self-reported depressive symptomatology of drug users with HCV
      who have not received interferon treatment was compared to that of uninfected
      drug users. METHODS: Subjects were 309 drug users not currently in substance
      abuse treatment who were participating in a National Institute on Drug Abuse
      project. Subjects completed the Center for Epidemiological Studies-Depression
      (CES-D) instrument and provided a blood sample for HCV testing. RESULTS:
      Serological findings revealed that 52.4% of the subjects tested positive for HCV
      antibodies. Of the HCV-positive subjects, 57.2% had significant depressive
      symptomatology, whereas only 48.2% of the HCV-negative subjects did, for an
      overall rate of 52.6%. The two groups also differed on two specific dimensions of
      depression, with the HCV-positive group scoring lower on the Positive Affect
      scale and higher on the Somatic/Retarded Activity scale. CONCLUSIONS: These
      findings reveal high levels of depressive symptomatology among drug users, as
      well as the possibility of a coexisting depressive syndrome with HCV infection.
      These findings raise the possibility that depression associated with interferon
      treatment may, at least partially, be accounted for by preexisting depression.
      Further research is needed to determine the nature and origins of depression in
      individuals in treatment with interferon for HCV with specific focus placed on
      determining the dimensions of depression associated with HCV infection and
      interferon treatment.

PMID- 9625129
TI  - Soluble CD44 and CD44v6 serum levels in patients with colorectal cancer are
      independent of tumor stage and tissue expression of CD44v6.
AB  - OBJECTIVES: Tissue overexpression of CD44 variants, especially CD44v6, and
      elevated serum concentrations of soluble CD44 variants (sCD44) have been
      demonstrated in patients with colorectal cancer and several other tumors. Our aim
      was to evaluate the clinical value of their measurement in colorectal cancer.
      METHODS: To examine the suitability of sCD44 and sCD44v6 as tumor markers in
      colorectal cancer these parameters were analyzed in serum of patients with
      colorectal cancer, inflammatory bowel disease, chronic renal failure, and
      controls. Tissue expression of CD44v6 in colorectal carcinomas was investigated
      by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: sCD44 and
      sCD44v6 levels were significantly elevated in most of the patient groups
      (medians, sCD44: 330-709 ng/ml; sCD44v6: 125-160 ng/ml) compared to controls
      (sCD44: 346 ng/ml; sCD44v6: 106.5 ng/ml). No difference was seen between
      colorectal cancer patients of different UICC (Union Internationale Contre le
      Cancer) stages and between patients with CD44v6-positive or -negative primary
      tumors. CONCLUSIONS: sCD44 and sCD44v6 concentrations showed no correlation to
      tumor burden or CD44v6 tissue expression. Sensitivity and specificity were low,
      compared to CEA. Therefore, in our view sCD44 and sCD44v6 measurement in
      screening or follow-up of patients with colorectal cancer is of very little
      clinical value.

PMID- 9625130
TI  - Expression of inducible nitric oxide synthase (iNOS) mRNA in inflamed esophageal
      and colonic mucosa in a pediatric population.
AB  - OBJECTIVE: Increasing evidence suggests that nitric oxide participates in the
      pathophysiology of intestinal barrier function/dysfunction and inflammation.
      Increases in inducible nitric oxide synthase (iNOS) mRNA and protein expression
      have been observed in colonic mucosal biopsies of adults with inflammatory bowel
      disease (IBD). It is unclear whether iNOS induction is specific for IBD or a
      reflection of nonspecific mucosal inflammation. Furthermore, the characteristics
      of iNOS mRNA expression in pediatric patients with gastrointestinal disorders
      remains ill-defined. Our objective was to examine the relationship between iNOS
      mRNA expression and gastrointestinal mucosal inflammation in a pediatric
      population. METHODS: Esophageal and colonic mucosal biopsies were obtained during
      endoscopy. Total RNA was isolated from these biopsies and reverse transcription
      polymerase chain reaction (RT-PCR) performed (35 PCR cycles) using two 20-bp
      primers that amplified a predicted 372-bp conserved iNOS mRNA fragment. RESULTS:
      Biopsies were obtained from 29 children (22 boys; mean age 10.6 yr [range 1.7
      16.5 yr]). Endoscopic and histological findings included normal esophageal mucosa
      (n = 3), esophagitis (n = 10), normal rectal mucosa (n = 2), ulcerative colitis
      (n = 10), and Crohn disease (n = 4). Evidence of iNOS mRNA was detected by PCR
      amplification in six of 10 patients with ulcerative colitis and in two of four
      patients with Crohn disease. However, iNOS mRNA was not amplified in any
      esophageal biopsy or in rectal mucosa biopsies with normal histology.
      CONCLUSIONS: These data indicate that upregulation of iNOS mRNA expression in
      colonic mucosa is a feature of IBD in children. iNOS mRNA expression is not
      upregulated in esophageal mucosa or in the absence of colonic inflammation.
      Further studies designed to determine the site- and cell-specificity of iNOS mRNA
      upregulation in mucosal biopsies from children with IBD may further illuminate
      the pathophysiology of these disorders.

PMID- 9625131
TI  - Maintenance treatment of ulcerative proctitis with mesalazine suppositories: a
      double-blind placebo-controlled trial. The Italian IBD Study Group.
AB  - OBJECTIVES: A multicenter double-blind placebo-controlled clinical study was
      conducted to evaluate the efficacy and tolerability of two different therapeutic
      schedules of mesalazine suppositories in patients with ulcerative proctitis.
      METHODS: From 1990 to 1993, 111 patients with ulcerative proctisis in remission,
      limited to the rectum (< or = 15 cm from anus), were enrolled. After obtaining
      informed consent, patients were randomized to three treatment groups: 500 mg
      mesalazine b.i.d. (36 patients), 500 mg mesalazine u.i.d. (40 patients), and
      placebo (35 patients). The treatment lasted 1 yr. Follow-up consisted of periodic
      clinical, endoscopic, and histological assessments. An endoscopic score > 1
      according to the Baron scale defined relapse occurrence. The three groups were
      homogeneous as regards main demographic, diagnostic, and prognostic features.
      RESULTS: The cumulative relapse rates at 12 months were 10% (95% confidence
      interval [CI]: 0-21) in the mesalazine b.i.d. group, 32% (95% CI: 16-49) in the
      mesalazine u.i.d. group, and 47% (95% CI: 29-65) in the placebo group. The
      comparison between the mesalazine b.i.d. group and the mesalazine u.i.d. group
      cumulative relapse rates gave a p value of 0.0334, whereas the corresponding
      comparison between the mesalazine b.i.d. group and the placebo group gave a p
      value of 0.007 (log-rank test). The dose-response relationship was statistically
      significant (p = 0.008 by Cox analysis). Two patients in the mesalazine b.i.d.
      group, two patients in the mesalazine u.i.d. group, and one patient in the
      placebo group withdrew from the study due to nonserious adverse events; four,
      three, and four patients per group, respectively, dropped out because of poor
      compliance. Two patients in the mesalazine u.i.d. group and two in the placebo
      group were lost to follow-up. CONCLUSIONS: The results of this study confirm the
      therapeutic efficacy of mesalazine suppositories in the maintenance treatment of
      ulcerative proctitis. According to our experience the most effective therapeutic
      schedule is 500 mg mesalazine b.i.d.

PMID- 9625132
TI  - Distal procto-colitis, natural cytotoxicity, and essential fatty acids.
AB  - OBJECTIVES: Recently, it has been postulated that patients with ulcerative
      colitis have altered natural cytotoxicity, in particular natural killer (NK) and
      lymphokine-activated killer (LAK) cell activities. These cellular mechanisms have
      been postulated to play an etiological role in the pathogenesis of the disease
      process. We have shown previously that the essential fatty acids (EFA)
      eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) specifically inhibit
      natural cytotoxicity. Our aim was to evaluate the role of omega-3 EFA in the
      modulation of natural cytotoxicity and disease activity in patients with distal
      procto-colitis. METHODS: In this pilot study patients were randomized into two
      groups. Each patient received either fish oil extract (EPA, 3.2 g, and DHA, 2.4
      g) (n = 9) or sunflower oil (placebo) (n = 9) daily in a double-blind manner for
      6 months. Monthly assessments of disease activity (clinical and sigmoidoscopic
      scores) and histological evaluation of mucosal biopsies were carried out. Also,
      the circulating levels and activities of NK and LAK cells, using flow cytometric
      analysis (CD16+ CD56+) and in vitro 51 chromium release assays (K562),
      respectively, were monitored. RESULTS: After 6 months' supplementation with EFA,
      there was improvement in the clinical activity compared with pretreatment
      evaluation. There was significant reduction in the sigmoidoscopic and
      histological scores in the EFA group compared with the placebo group. Essential
      fatty acid supplementation for 6 months also induced significant reduction in the
      circulating numbers of CD16+ and CD56+ cells and the cytotoxic activity of NK
      cells, compared with the placebo group. CONCLUSIONS: This pilot study has
      demonstrated that omega-3 fatty acids can suppress natural cytotoxicity and
      reduce disease activity in patients with distal procto-colitis. These findings
      suggest a therapeutic strategy for managing patients with inflammatory bowel
      disease.

PMID- 9625133
TI  - Visceral varicella-zoster after bone marrow transplantation: report of a case
      series and review of the literature.
AB  - OBJECTIVES: Infection with varicella-zoster virus after bone marrow
      transplantation (BMT) is a common cause of morbidity and mortality. Visceral
      involvement with varicella-zoster may be incorrectly ascribed to graft-versus
      host disease, resulting in delayed diagnosis and misguided therapy. METHODS: A 4
      yr retrospective chart review was performed to determine the presenting symptoms
      and clinical outcome of visceral varicella-zoster virus infection in BMT
      recipients. RESULTS: Ten BMT recipients who subsequently developed visceral
      varicella-zoster virus infection were identified. The mean age at diagnosis was
      40 yr (range 27-56 yr). Primary hematological malignancies were leukemia (N = 7),
      myelodysplasia (N = 2), and myelofibrosis (N = 1). Bone marrow transplants in
      affected patients were autologous (N = 2), related allogeneic (N = 5), or matched
      unrelated allogeneic (N = 3). The mean time interval from BMT to symptomatic
      visceral varicella-zoster virus infection was 153 days (range 60-280 days).
      Presenting symptoms included abdominal pain in all patients, nausea (60%), fever
      > 38 degrees C (60%), vomiting (50%), pneumonitis (50%), skin rash (40%), and
      diarrhea (30%). All patients had moderately or profoundly elevated
      aminotransferases and most had elevated pancreatic enzymes (80%). The mean time
      interval from the development of abdominal pain to the characteristic skin rash
      and then diagnosis was 6 and 7 days, respectively (range 4-10 and 4-14 days).
      Active graft-versus-host disease had previously been documented in five of the
      eight allogeneic BMT recipients. Immunosuppressive medications were increased at
      the onset of the abdominal pain in seven of these eight patients for suspected
      exacerbation of graft-versus-host disease. After recognition of varicella
      infection, antiviral therapy was promptly initiated; despite this, mortality was
      still 50%. CONCLUSIONS: Visceral involvement with varicella-zoster virus
      infection can occur as a late complication after both allogeneic and autologous
      BMT. In these cases, symptoms of severe abdominal pain with associated nausea,
      vomiting, and diarrhea and elevated liver and pancreatic enzymes preceded the
      vesicular skin eruption and were confused with graft-versus-host disease. With
      the increasing application of high-dose chemotherapy followed by stem cell rescue
      for both hematological and solid tumors, clinicians should be aware of this
      potentially treatable and often lethal complication.

PMID- 9625134
TI  - Benefit of uncooked cornstarch in the management of children with dumping
      syndrome fed exclusively by gastrostomy.
AB  - OBJECTIVES: Children with dumping syndrome fed exclusively by gastrostomy are
      difficult to manage because liquid diets are given directly into the antrum. The
      gastric contents are emptied rapidly into the small intestine, with consequent
      hyperglycemia followed by a delayed hypoglycemia and multiple, often
      debilitating, symptoms. Uncooked cornstarch is a complex carbohydrate that
      provides a slow and continuous glucose source and may delay gastric emptying. The
      objective of this study was to determine the efficacy of uncooked cornstarch in
      the treatment of these children. METHODS: The medical records of eight children
      with dumping syndrome fed exclusively by gastrostomy were reviewed. Dumping
      syndrome was diagnosed if there was consistent symptomatology, rapid gastric
      emptying, and abnormal glucose measurements after a glucose tolerance test.
      Enough uncooked cornstarch to match hepatic glucose production for 4 h was added
      to control hypoglycemia, and the feeding formula was modified to control
      hyperglycemia. RESULTS: All patients had debilitating symptoms. Weight z-score on
      admission was -2.31 +/- 0.29. Glucose shifts were controlled in all. There was a
      significant difference between the maximum (221.3 +/- 19.3 mg/dl vs 121.3 +/- 6.9
      mg/dl; p < 0.008) and minimum serum glucose (47 +/- 7.8 mg/dl vs 65.6 +/- 4
      mg/dl; p < 0.04) before and after uncooked cornstarch. Weight increased from
      11.87 +/- 1.4 kg to 15.10 +/- 2.3 kg (p = 0.06). In seven patients, bolus
      feedings were successfully administered, and symptoms improved or resolved.
      CONCLUSIONS: Uncooked cornstarch controlled the glucose shifts, resolved most of
      the symptoms, allowed bolus feedings, and enhanced weight gain in these children.

PMID- 9625135
TI  - Nitrofurantoin-induced hepatotoxicity mediated by CD8+ T cells.
AB  - Nitrofurantoin is a synthetic nitrofuran commonly used for the treatment and
      prophylaxis of urinary tract infections. We describe the case of a 75-yr-old
      woman who was taking nitrofurantoin as prophylaxis against recurrent urinary
      tract infections, and who subsequently developed pulmonary and hepatic toxicity.
      We postulate that a breakdown product of the drug or the drug itself complexed to
      an endogenous peptide is presented by the class I HLA antigen on the hepatocyte
      cell membrane, inducing cytotoxic T cell activation and subsequently, hepatocyte
      death.

PMID- 9625136
TI  - Possible cholestatic injury from ranitidine with a review of the literature.
AB  - Although one of the histamine-2 (H2) receptor antagonists, oxmetidine, has been
      shown to be intrinsically hepatotoxic, overt liver injury attributable to the
      commonly used analogues such as ranitidine is rare, given the millions of
      patients who have received this medication. However, isolated cases of hepatitis
      associated with ranitidine have been reported in the literature since the early
      1980s when this drug was first introduced. We report a case of cholestatic
      hepatitis associated with ranitidine use. Liver biopsy showed diffuse panacinar
      canalicular cholestasis and cholestatic rosettes in zone 3. The clinical syndrome
      and the laboratory abnormalities resolved completely after discontinuation of the
      drug. There have been a few other published reports of ranitidine associated
      acute cholestatic hepatitis, and in this case ranitidine was temporally related
      to the onset of symptoms and liver enzyme abnormalities. With recent over-the
      counter (OTC) availability of the H2 receptor antagonists and the increasing use
      of these drugs in the general population, physicians need to be aware of this
      rare but potentially serious side effect of ranitidine.

PMID- 9625137
TI  - Hepatic cystadenoma: an unusual presentation.
AB  - A 53-yr-old woman with a history of hepatic cystadenoma 25 yr before presented
      with a simple hepatic cyst, which evolved over 9 yr into a complex cystadenoma
      with septations and internal bleeding. She was treated with a left hepatectomy.
      Review of the literature shows that hepatic cystadenomas, although rare,
      frequently can recur years later and have potential for malignant transformation.
      Histologic similarities of one variant with ovarian stroma raises interesting
      possibilities regarding the origin of these lesions. The best treatment results
      are obtained with radical excision.

PMID- 9625139
TI  - Duodenal hemangioendothelioma: a case report.
AB  - Epithelioid hemangioendothelioma is extremely rare. A patient with an epithelioid
      hemangioendothelioma presenting as an annular mass encircling the second portion
      of the duodenum is described. We believe this to be the first such lesion in this
      location reported.

PMID- 9625138
TI  - Liver transplantation for disulfiram-induced hepatic failure.
AB  - Fulminant hepatitis is a rare but potentially fatal adverse reaction that may
      occur after the use of disulfiram. A patient without a known history of liver
      disease was transplanted for fulminant hepatic failure secondary to disulfiram. A
      high index of suspicion and aggressive therapeutic approaches are essential for
      the prompt diagnosis and treatment of disulfiram-induced hepatic failure. The
      clinical presentation, histopathology, treatment, and all cases of disulfiram
      induced hepatic failure reported in the English literature are reviewed. The role
      of orthotopic liver transplantation in a case of disulfiram-induced hepatic
      failure is discussed.

PMID- 9625140
TI  - Familial occurrence of gastric carcinoid tumors associated with type A chronic
      atrophic gastritis.
AB  - We present here familial occurrence of two patients with gastric carcinoid. Both
      patients, a sister and older sister, had type A chronic atrophic gastritis with
      hypergastrinemia. This is the first case report of familial occurrence of gastric
      carcinoid associated with type A chronic atrophic gastritis in the world
      literature. The possible mechanism of familial occurrence in the patients is
      discussed.

PMID- 9625141
TI  - Hodgkin's disease diagnosed by endoscopic ultrasound-guided fine needle
      aspiration of a periduodenal lymph node.
AB  - Hodgkin's disease rarely presents as obstructive jaundice. We report a case of
      Hodgkin's disease arising in periduodenallymph nodes, presenting with biliary
      obstruction, definitively diagnosed on cytologic material obtained by
      endosonographically-guided real-time fine needle aspiration biopsy and confirmed
      at laparotomy. The medical literature pertaining to the use of endosonography and
      fine needle aspiration biopsy for pancreatic lesions and abdominal lymphoma is
      reviewed. Currently available data support the use of fine needle aspiration
      biopsy in establishing the diagnosis of lymphoma. This case highlights the
      utility of endoscopic ultrasonography with endosonographically guided real-time
      fine needle aspiration biopsy in diagnosing and managing patients with
      extrahepatic biliary obstruction or suspected abdominal lymphoma. Pairing
      endosonographically guided real-time fine needle aspiration biopsy with on-site
      cytologic assessment and immediate specimen triage can lead to definitive
      diagnosis of abdominal lymphoma, avoiding surgical intervention in many cases.

PMID- 9625142
TI  - Acute hepatitis, autoimmune hemolytic anemia, and erythroblastocytopenia induced
      by ceftriaxone.
AB  - An 80-yr-old man developed acute hepatitis shortly after ingesting oral
      ceftriaxone. Although the transaminases gradually returned to baseline after
      withholding the beta lactam antibiotic, there was a gradual increase in serum
      bilirubin and a decrease in hemoglobin concentration caused by an autoimmune
      hemolytic anemia and erythroblastocytopenia. These responded to systemic steroids
      and immunoglobulins. Despite the widespread use of these agents this triad of
      side effects has not previously been reported in connection with beta lactam
      antibiotics.

PMID- 9625143
TI  - Idiopathic pulmonary fibrosis associated with rectal carcinoma--a paraneoplastic
      syndrome or coincidence?
AB  - The association between lung cancer and idiopathic pulmonary fibrosis (IPF) is
      well documented, complicating > or = 10% of cases involving IPF. This association
      is considered to be a result of neoplastic degeneration, rather than a
      paraneoplastic phenomenon. However, rectal carcinoma has only rarely been linked
      to paraneoplastic manifestations. We describe a young patient with IPF that
      preceded the appearance of rectal carcinoma by 6 mo. The possible association
      between the two disorders is discussed.

PMID- 9625144
TI  - New hope for AIDS patients.

PMID- 9625145
TI  - Inflammatory bowel disease activity--the role of blood flow.

PMID- 9625146
TI  - Which type of alcohol is easier on the gut?

PMID- 9625147
TI  - Monitoring Helicobacter pylori eradication therapy.

PMID- 9625148
TI  - Re: Uchida et al. Endoscopic lithotomy of common bile duct stones with sublingual
      nitroglycerin and guidewire.

PMID- 9625149
TI  - Should we cut or dilate the sphincter? That may depend on whether it is primary
      or secondary common bile duct stones.

PMID- 9625150
TI  - Cholangiocarcinoma presenting as Trousseau's syndrome.

PMID- 9625151
TI  - Altered bone metabolism in inflammatory bowel disease.

PMID- 9625152
TI  - Multiple malignant melanoma metastasis to the gastrointestinal tract.

PMID- 9625153
TI  - Hepatitis C virus RNA detection in oral lichen planus tissue.

PMID- 9625154
TI  - Accidental isopropyl alcohol enema leading to coma and death.

PMID- 9625155
TI  - Helicobacter pylori urease inhibition and ammonia levels in cirrhotic patients.

PMID- 9625156
TI  - The cause of diarrhea in hospitalized patients.

PMID- 9625157
TI  - Natural history of residual carcinoma in situ components at the resection margin
      after esophagectomy for a squamous cell carcinoma of the esophagus.

PMID- 9625158
TI  - Brucellosis and hepatocellular carcinoma: just a coincidence?

PMID- 9625159
TI  - Omeprazole and fundic gland polyps.

PMID- 9625160
TI  - Re: black esophagus.

PMID- 9625161
TI  - 13th World Congress of Cardiology. Rio De Janeiro, April 26-30, 1998. Abstracts
      on CD-ROM.

PMID- 9625162
TI  - Primary peritoneal carcinoma can have multifocal origins: implications for
      prophylactic oophorectomy.

PMID- 9625163
TI  - Prognostic applications of the epidermal growth factor receptor and its ligand,
      transforming growth factor-alpha.

PMID- 9625164
TI  - Cancer and arthritis share underlying processes.

PMID- 9625165
TI  - Surgeons have critical role in genetic testing decisions, medical, legal experts
      say.

PMID- 9625166
TI  - Changes at FDA may speed drug approval process and increase off-label use.

PMID- 9625167
TI  - Middle East Cancer Consortium stays on track to collect data.

PMID- 9625168
TI  - The Michigan health kiosk: cancer info on the go.

PMID- 9625169
TI  - Relationship between estrogen levels, use of hormone replacement therapy, and
      breast cancer.
AB  - We sought to determine the strength of the evidence suggesting that estrogen and
      postmenopausal replacement hormones play a role in the development of breast
      cancer. We reviewed the existing English language literature in MEDLINE on
      hormones and breast cancer, including reports on cell proliferation and
      endogenous hormone levels, as well as epidemiologic studies of the relationship
      between the use of postmenopausal hormones and the risk of breast cancer in
      women. A factor that increases the probability that cancer will develop in an
      individual has been defined as a cancer cause. The Hill criteria for
      demonstrating a link between environmental factors and disease were used to
      review the evidence for a causal relationship between female hormones and breast
      cancer. We found evidence of a causal relationship between these hormones and
      breast cancer, based on the following criteria: consistency, dose-response
      pattern, biologic plausibility, temporality, strength of association, and
      coherence. The magnitude of the increase in breast cancer risk per year of
      hormone use is comparable to that associated with delaying menopause by a year.
      The positive relationship between endogenous hormone levels in postmenopausal
      women and risk of breast cancer supports a biologic mechanism for the
      relationship between use of hormones and increased risk of this disease. The
      finding that the increase in risk of breast cancer associated with increasing
      duration of hormone use does not vary substantially across studies offers further
      evidence for a causal relationship. We conclude that existing evidence supports a
      causal relationship between use of estrogens and progestins, levels of endogenous
      estrogens, and breast cancer incidence in postmenopausal women. Hormones may act
      to promote the late stages of carcinogenesis among postmenopausal women and to
      facilitate the proliferation of malignant cells. Strategies that do not cause
      breast cancer are urgently needed for the relief of menopausal symptoms and the
      long-term prevention of osteoporosis and heart disease.

PMID- 9625170
TI  - Levels of TGF-alpha and EGFR protein in head and neck squamous cell carcinoma and
      patient survival.
AB  - BACKGROUND: The most accurate predictor of disease recurrence in patients treated
      for head and neck squamous cell carcinoma is, at present, the extent of regional
      lymph node metastasis. Since elevated levels of epidermal growth factor receptor
      (EGFR) and of its ligand, transforming growth factor-alpha (TGF-alpha), have been
      detected in primary tumors of patients with head and neck squamous cell
      carcinoma, we determined whether tumor levels of these proteins were of
      prognostic importance. METHODS: Monoclonal antibodies specific for EGFR and TGF
      alpha were used for immunohistochemical detection of each protein in tissue
      sections of primary tumors from 91 patients who were treated by surgical
      resection. Levels of immunoreactive EGFR and TGF-alpha were quantified by use of
      a computerized image analysis system and were normalized to appropriate
      standards. The logrank test and proportional hazards regression analysis were
      used to calculate the probability that EGFR and TGF-alpha levels were associated
      with disease-free survival (i.e., no recurrence of cancer) and cause-specific
      survival (i.e., patients do not die of their disease). All P values were two
      sided. RESULTS: When tumor levels of EGFR or TGF-alpha were analyzed as
      continuous variables, disease-free survival and cause-specific survival were
      reduced among patients with higher levels of EGFR (both P = .0001) or TGF-alpha
      (both P = .0001). In a multivariate analysis, tumor site, tumor level of EGFR,
      and tumor level of TGF-alpha were statistically significant predictors of disease
      free survival; in a similar analysis, regional lymph node stage and tumor levels
      of EGFR and of TGF-alpha were significant predictors of cause-specific survival.
      CONCLUSION: Quantitation of EGFR and TGF-alpha protein levels in primary head and
      neck squamous cell carcinomas may be useful in identifying subgroups of patients
      at high risk of tumor recurrence and in guiding therapy.

PMID- 9625171
TI  - Trends and outcomes of outpatient mastectomy in elderly women.
AB  - BACKGROUND: Considerable public attention has focused on the use of outpatient
      mastectomy and has resulted in numerous legislative proposals to mandate a
      minimum hospital stay following mastectomy. To date, only limited scientific data
      are available regarding the use and the outcomes of outpatient mastectomy. The
      purpose of this study was to provide population-based information on trends and
      outcomes for outpatient mastectomy in elderly women. METHODS: Medicare data for
      elderly women with fee-for-service coverage were examined for trends and regional
      variation in the use of outpatient mastectomy. Logistic regression was used to
      identify patient and provider characteristics associated with having an
      outpatient mastectomy, and outcomes were assessed by calculating the risk of
      being rehospitalized and the reasons for rehospitalization. RESULTS: From 1986
      through 1995, the proportion of mastectomies performed on an outpatient basis
      increased from virtually 0% to 10.8%. Outpatient mastectomies were more likely to
      be performed on women with no coexisting health problems in hospitals that were
      for-profit or non-teaching or in large metropolitan statistical areas. Women
      undergoing outpatient mastectomy had substantially higher rates of
      rehospitalization within 30 days than women with a 1-day stay in the hospital.
      Both groups had comparable rates of rehospitalization for complications
      definitely related to their surgery. The percentage of women who required
      rehospitalization was low, and the actual number of women rehospitalized was
      relatively small. CONCLUSIONS: We conclude that the risks from outpatient
      mastectomy are modest, although ongoing monitoring of outcomes and assessment of
      patient satisfaction are needed.

PMID- 9625172
TI  - Molecular evidence for multifocal papillary serous carcinoma of the peritoneum in
      patients with germline BRCA1 mutations.
AB  - BACKGROUND: Papillary serous carcinoma of the peritoneum (PSCP) diffusely
      involves peritoneal surfaces, while it spares or only superficially involves the
      ovaries. PSCP is histologically indistinguishable from serous epithelial ovarian
      carcinoma, and it may develop years after oophorectomy. The molecular
      pathogenesis of PSCP remains unresolved, although preliminary data suggest a
      multifocal origin in some cases. Patients with germline BRCA1 mutations may
      develop PSCP in addition to breast and ovarian carcinomas. The purpose of this
      study was to utilize the androgen receptor (AR) gene locus to test the hypothesis
      that some cases of PSCP have a multifocal origin and to determine if patients
      with germline BRCA1 mutations develop multifocal PSCP. METHODS: Specimens of
      normal and tumor tissues from 22 women with PSCP were obtained, and DNA was
      extracted. The AR gene locus was evaluated for patterns of loss of heterozygosity
      (LOH) and X-chromosome inactivation. The methylation-sensitive Hpa II restriction
      enzyme was used to differentiate the active and inactive X chromosomes. Germline
      BRCA1 mutation status of the patients was determined previously. RESULTS: Genetic
      analysis of tumor specimens indicated that five (23%) of 22 case subjects had
      patterns of selective LOH at the AR locus, consistent with multifocal, polyclonal
      disease origin. Two patients with selective LOH also had alternating X-chromosome
      inactivation patterns. Patients with germline BRCA1 mutations were more likely to
      have evidence of multifocal disease (two-sided Fisher's exact test, P = .01).
      CONCLUSIONS: Our results show that PSCP has a multifocal origin in at least some
      cases. Furthermore, patients with germline BRCA1 mutations are more likely to
      develop multifocal PSCP than are patients without BRCA1 mutations.

PMID- 9625173
TI  - Scintimammographic analysis of nonpalpable breast lesions previously identified
      by conventional mammography.
AB  - BACKGROUND: In randomized trials, screening mammography has led to decreased
      mortality from breast cancer. However, the low positive predictive value of
      mammography (i.e., the proportion of patients with a positive test result who
      actually have breast cancer) results in a large number of unnecessary biopsies.
      We determined whether scintimammography with technetium-99m-sestamibi is a useful
      supplemental diagnostic tool for women with nonpalpable breast abnormalities
      identified by conventional mammography. METHODS: Scintimammography was performed
      preoperatively on 70 women who were 31-66 years of age (mean age and median age =
      51 years). These women had nonpalpable breast abnormalities identified by
      conventional mammography; subsequently, a needle-localization excisional biopsy
      of each suspicious lesion was performed. Scintimammographic images were
      interpreted independently by two nuclear medicine physicians who were blinded to
      all clinical and pathologic data, and an interobserver variation analysis was
      performed. RESULTS: Interobserver variation analysis of the scintimammographic
      findings showed an agreement for breast diagnosis of 97% and a kappa coefficient
      of 0.90. Comparison of scintimammographic findings and histopathologic results
      revealed that the sensitivity (proportion of patients with breast cancer who had
      a positive test result), the specificity (proportion of patients without breast
      cancer who had a negative test result), the positive predictive value and the
      negative predictive value (proportion of patients with a negative test result who
      actually did not have breast cancer) of scintimammography were 56% (95%
      confidence interval [CI] = 23%-85%), 87% (95% CI = 75%-94%), 38% (95% CI = 15%
      68%), and 93% (95% CI = 82%-98%), respectively. Four of nine breast cancers were
      not detected by scintimammography. CONCLUSION: Because of excellent interobserver
      agreement, scintimammography provides an objective way of detecting primary
      breast carcinoma. In view of its low sensitivity and positive predictive value,
      however, scintimammography is not currently recommended as a screening test in
      patients with nonpalpable positive mammographic findings.

PMID- 9625174
TI  - A new prognostic score for survival of patients with chronic myeloid leukemia
      treated with interferon alfa. Writing Committee for the Collaborative CML
      Prognostic Factors Project Group.
AB  - BACKGROUND: Interferon alfa is a conservative and widely used alternative to bone
      marrow transplantation in treatment of patients with early chronic myeloid
      leukemia (CML). A meta-analysis was conducted to develop a reliable prognostic
      scoring system for estimation of survival of patients with CML treated with
      interferon alfa. METHODS: Patients treated in prospective studies, including
      major randomized trials, were separated into learning and validation samples. Cox
      regression analysis and the minimum P-value approach were used to identify
      prognostic factors for patient survival and to discover groups in the learning
      sample with the greatest differences in survival. These findings were then
      validated by applying the new scoring system to patients in the validation
      sample. RESULTS: We collected data on 1573 patients who were participants in 14
      studies involving 12 institutions; 1303 patients (learning sample, n = 981;
      validation sample, n = 322) were eligible for inclusion in this analysis, and
      their median survival time was 69 months (range, 1-117 months). Because two
      previously described prognostic scoring systems failed to discriminate risk
      groups satisfactorily, we developed a new scoring system that utilizes the
      following covariates: age, spleen size, blast count, platelet count, eosinophil
      count, and basophil count. Among 908 patients with complete data in the learning
      sample, three distinct risk groups were identified (median survival times of 98
      months [n = 369; 40.6%], 65 months [n = 406; 44.7%], or 42 months [n =
      133;14.6%]; two-sided logrank test, P< or =.0001). The ability of the new scoring
      system to discriminate these risk groups was confirmed by analysis of 285
      patients with complete data in the validation sample (two-sided logrank test, P =
      .0002). CONCLUSIONS: A new prognostic scoring system for estimating survival of
      patients with CML treated with interferon alfa has been developed and validated
      through use of a large dataset.

PMID- 9625175
TI  - Identification of a pseudogene that can masquerade as a mutant allele of the
      PTEN/MMAC1 tumor suppressor gene.

PMID- 9625176
TI  - Cell line designation change: multidrug-resistant cell line in the NCI anticancer
      screen.

PMID- 9625177
TI  - Influence of genistein and daidzein on Brca1 protein levels in human breast cell
      lines.

PMID- 9625178
TI  - Diagnostic drift in the reporting of cancer incidence.

PMID- 9625179
TI  - Re: Expression of somatostatin receptor subtype 1-5 genes in human pancreatic
      cancer.

PMID- 9625180
TI  - Home environmental hazards and the risk of fall injury events among community
      dwelling older persons. Study to Assess Falls Among the Elderly (SAFE) Group.
AB  - OBJECTIVE: To determine if home environmental hazards increase the risk of fall
      injury events among community-dwelling older persons. DESIGN: Population-based
      case-control study. SETTING: South Miami Beach, Florida. PARTICIPANTS: 270
      persons aged 65 years and older who sought treatment at six area hospitals for
      injuries resulting from falls within the dwelling unit and 691 controls,
      frequency matched for sex and age, selected randomly from Health Care Financing
      Administration (Medicare) files. MAIN INDEPENDENT VARIABLES: The home environment
      of each person, assessed directly by interviewers using a standardized
      instrument. RESULTS: Environmental hazards were present in nearly all dwelling
      units. After adjusting for important confounding factors, most of these hazards
      were not associated with an increased risk of fall injury events among most older
      persons. Increasing numbers of tripping hazards, or total hazards in the dwelling
      unit, did not increase the risk of fall injury events, nor was there an
      increasing trend in risk. CONCLUSIONS: Current fall-prevention strategies of
      finding and changing all environmental hazards in all community-dwelling older
      persons' homes may have less potential effect than previously thought. The
      usefulness of grab bars, however, appears to warrant further evaluation.

PMID- 9625181
TI  - The association between chronic illness and functional change among participants
      in a comprehensive geriatric assessment program.
AB  - OBJECTIVE: To examine the association between chronic illness and functional
      status change during a 3-year period in older people enrolled in an in-home
      comprehensive geriatric assessment (CGA) and preventive care program. DESIGN:
      Secondary analysis of data from a longitudinal cohort study. SETTING: Santa
      Monica, California. PARTICIPANTS: Two hundred two community-dwelling older
      persons (mean age at baseline was 81 years, 70% were women, and 72% reported good
      health) randomized to the intervention group in a trial of in-home comprehensive
      geriatric assessment and preventive care. MEASUREMENTS: We studied 13 common
      chronic illnesses/conditions determined clinically from an annual comprehensive
      evaluation by gerontologic nurse practitioners (GNPs) in consultation with study
      geriatricians. These target conditions included hypertension, osteoarthritis,
      coronary artery disease, obesity, undernutrition, urinary incontinence, sleep
      disorders, falls, gait/balance disorders, hearing and vision deficits,
      depression, and unsafe home environment. The dependent variable was functional
      change as measured by instrumental activities of daily living (IADL) and basic
      activities of daily living (BADL) assessed at baseline and annually for 3 years
      by independent research personnel. Potential confounding variables, including
      comorbid conditions and other subject characteristics, were controlled for in the
      analyses. RESULTS: Although functional status was similar at baseline, the
      presence of certain target conditions in this sample was associated significantly
      with functional decline in IADL and BADL during the 3-year period. Four
      conditions (gait/balance disorders, depression, unsafe home environment, and
      coronary artery disease) were associated with significant declines in IADL, and
      four conditions (gait/balance disorders, depression, hypertension, and urinary
      incontinence) were associated with significant declines in BADL. Conversely,
      subjects with obesity had no significant change in IADL or BADL throughout the
      study period and had less decline in IADL compared with nonobese subjects.
      CONCLUSIONS: Certain chronic conditions, particularly gait/balance disorders and
      depression, are associated with significant decline in functional status in older
      persons who receive CGA. These findings may help identify older persons at risk
      for greatest functional decline despite participation in CGA and may also suggest
      the need for more effective intervention strategies in these individuals.

PMID- 9625182
TI  - The impact of urge urinary incontinence on quality of life: importance of
      patients' perspective and explanatory style.
AB  - OBJECTIVES: The impact of urinary incontinence (UI) on health-related quality of
      life (QoL) is significant yet variable, but little is known about patient-defined
      content areas regarding the influence of UI on QoL and whether patient-specific
      factors correlate with specific content areas of UI-related QoL. In order to
      identify the most valid content areas for a new UI-related QoL questionnaire, our
      primary goal was to determine the content areas of greatest concern regarding UI
      related QoL among older persons with urge incontinence. The second goal was to
      examine the possible role of patients' explanatory style as a mediator of UI
      impact on health-related QoL. Data on the questionnaire will be presented
      elsewhere. DESIGN: Focus groups comprising urge-incontinent persons were used to
      obtain verbatim descriptions of the impact of UI on QoL. SETTING: A university
      affiliated tertiary hospital. PARTICIPANTS: Community-dwelling women (n = 25) and
      men (n = 5) more than 60 years of age, with urge incontinence, recruited from
      newspaper, newsletter, and radio advertisements. MEASUREMENTS: Qualitative
      content analysis of focus group transcripts was used to determine QoL items.
      These were compared with previously described UI-related QoL items obtained from
      the literature. Subjects' statements regarding causes of UI were evaluated for
      predominant explanatory style. RESULTS: Thirty-two UI-related QoL items were
      identified, more than half of which were not described previously. Compared with
      expert-defined UI-related QoL items from the literature, patient-defined items
      focused more on coping with embarrassment and interference from UI than on
      prevention of actual activity performance. Explanatory statements were made
      frequently by patients talking about their UI. Although positive style
      explanatory statements were most common, they did not correlate with any QoL
      items. By contrast, there was a significant correlation between negative
      explanatory style and six specific UI-related QoL items. CONCLUSIONS: Focus
      groups of older persons with urge incontinence suggest that experts and patients
      view the impact of urge UI on QoL differently. Whereas experts focus more on
      functional impact, patients more often cite the impact of UI on their emotional
      well-being and on the interruption of activities. In addition, the association
      between negative explanatory style and specific UI-related QoL items suggests
      that explanatory style may be an important mediator of patients' perceptions of
      UI-related QoL.

PMID- 9625183
TI  - The association of urinary incontinence with poor self-rated health.
AB  - OBJECTIVES: To assess whether urinary incontinence (UI) and its severity are
      associated with poor self-rated health in a national sample of community-living
      older adults and whether this relationship persists after controlling for
      confounding attributable to functional status, comorbidity, and demographic
      factors. DESIGN: A cross-sectional analysis using multivariate logistic
      regression. SETTING: Subjects were from the 1990-1991 National Survey of Self
      Care and Aging (N = 3485), a random sampling in geographic clusters of community
      dwelling Medicare beneficiaries 65 years of age or older in the contiguous United
      States. MEASURES: The responses to an interviewer-administered questionnaire
      regarding urinary incontinence, Basic Activities of Daily Living (BADL),
      Instrumental Activities of Daily Living (IADL), Mobility Activities of Daily
      Living (MADL), age, gender, place of residence, race, education, need for proxy
      response to the survey, and number of medical conditions. RESULTS: Unadjusted
      analysis showed the presence of urinary incontinence to be associated with poor
      self-rated health (OR 2.7, 2.1-3.3). With gender, number of comorbid conditions,
      race, IADL impairment, and interaction terms of incontinence/race and
      incontinence/IADL in the final model, UI was associated with poor self-rated
      health in certain subgroups. White subjects with no IADL impairment and mild
      moderate incontinence had an OR of 2.0 (95% CI 1.5-2.9) and those with severe
      incontinence had an OR of 4.5 (95% CI 2.4-8.4) of rating their health as poor,
      whereas those with no IADL impairment and no incontinence were the referent
      group. For those with a lot of difficulty performing one or more IADL activity,
      the association of UI and poor self-rated health was weak. For non-white
      subjects, there was no association, or a very weak association, of UI and poor
      self-rated health. CONCLUSION: In this national sample, urinary incontinence was
      independently and positively associated with poor self-rated health after
      adjustment for age, comorbidity, and frailty for most community-dwelling older
      adults. This association between UI and poor self-rated health was weaker and
      statistically insignificant when IADL impairment was present or in non-white
      subjects. Further research is indicated to better understand the impact of
      urinary incontinence in specific cultural settings.

PMID- 9625184
TI  - A nonpharmacologic sleep protocol for hospitalized older patients.
AB  - OBJECTIVES: To evaluate the feasibility of and adherence to a nonpharmacologic
      sleep protocol targeted to nurses for acutely ill older patients and to test the
      effectiveness of the protocol on enhancing sleep and reducing sedative-hypnotic
      drug (SHD) use. DESIGN: Prospective cohort study. SETTING: A 34-bed general
      medical unit in a university-affiliated teaching hospital. PARTICIPANTS: A total
      of 175 consecutive admissions aged 70 years or older. INTERVENTION: A
      nonpharmacologic sleep protocol consisting of a back rub, warm drink, and
      relaxation tapes was administered by nursing personnel to patients who complained
      of difficulty initiating sleep or who requested a SHD. After 1 hour, if the
      patient still requested it, the nurse administered the SHD. MEASUREMENTS: The
      main outcomes of sleep quality and SHD use were measured by patient interview and
      chart abstraction. Feasibility and adherence to the protocol were tracked daily
      by patient and nurse interviews and chart abstraction. RESULTS: A cohort of 111
      patients, mean age 79.3 (+/- 6.4), 68% women, received the sleep protocol.
      Patients required the protocol for a mean of 4.9 days per patient, totalling 539
      patients-days. The overall adherence rate was 400/539 (74%) patient-days. The
      rate of complete nonadherence was 139/539 (26%), with reasons for nonadherence
      including nurse nonadherence in 30 (6%), patient refusal in 104 (19%), and
      medical contraindications in five (1%). The quality of sleep correlated strongly
      with the number of parts of the protocol received, suggesting a dose-response
      relationship, with the highest correlation for receiving two to three parts (p =
      .64, P < 0.001). The sleep protocol was successful in reducing SHD use from the
      baseline preintervention rate of 51/94 (54%) to 34/111 (31%) (P < .002). The
      sleep protocol had a stronger association with quality of sleep (p = .75, P =
      .001) than did SHDs (p = .07, P = .45). However, chronic SHD users were more
      likely to refuse the protocol than nonusers (64% vs 41%, P < .03) and received
      SHDs 4.5 times more often than nonusers (67% vs 15%, P = .001). CONCLUSION: The
      nonpharmacologic sleep protocol provides a feasible, effective, and nontoxic
      alternative to SHDs to promote sleep in older hospitalized patients. Use of the
      protocol can substantially decrease use of SHDs.

PMID- 9625185
TI  - The clinical utility of a six-minute walk test in peripheral arterial occlusive
      disease patients.
AB  - OBJECTIVES: To determine the test-retest reliability of the distance covered and
      the steps taken to complete a 6-minute walk test by peripheral arterial occlusive
      disease (PAOD) patients with intermittent claudication. To determine the
      relationship between the total distance and steps covered during the 6-minute
      walk test and clinical measures of PAOD severity. DESIGN: Cross-sectional design.
      SETTING: The Claude Pepper Older Americans Independence Center at the University
      of Maryland at Baltimore. PARTICIPANTS: Sixty-four PAOD patients between the ages
      of 45 and 88 years (age = 68 +/- 7 years, ankle/brachial index (ABI) = .61 +/-
      .19) were recruited from the Vascular Clinic at the Baltimore Veterans Affairs
      Medical Center and from radio and newspaper advertisements. MEASUREMENTS:
      Patients were assessed on a 6-minute walk test and a treadmill graded exercise
      test. A second 6-minute walk test was administered approximately 1 week later.
      Patients also were characterized in regard to blood pressure in the arms and
      legs, ABI, anthropometry, body composition, and physical activity. RESULTS: The
      distances walked during the two 6-minute walk tests were similar (350 +/- 78 m vs
      360 +/- 73 m), resulting in a high reliability coefficient (R = .94) and a low
      coefficient of variation (10.4%). The total steps taken during the 6-minute walk
      test also were similar (562 +/- 113 steps vs 587 +/- 107 steps), resulting in a
      high reliability coefficient (R = .90) and a low coefficient of variation
      (11.7%). Furthermore, the 6-minute walking distance correlated with the distances
      to onset (r = .346, P = .007) and with maximal claudication pain (r = .525, P <
      .001) during the treadmill test as well as with ABI (r = .552, P < .001).
      CONCLUSION: The 6-minute walk test yields highly reliable measurements, which are
      related to the functional and hemodynamic severity of PAOD, in patients with
      intermittent claudication.

PMID- 9625186
TI  - Apolipoprotein E phenotypes, dementia and mortality in a prospective population
      sample.
AB  - OBJECTIVE: To study the relationships between apoE phenotypes, dementia, and
      mortality. SETTING: A population-based study in Helsinki, Finland (the Helsinki
      Ageing Study). DESIGN: A prospective birth cohort study with 5-year follow-up.
      PARTICIPANTS: A total of 550 subjects of three birth cohorts of 75 (n = 182), 80
      (n = 185), and 85 (n = 183) years of age. MEASUREMENTS: ApoE phenotype was
      determined from baseline blood samples. The cognitive function of the subjects
      was tested at baseline and at a 5-year follow-up using the Mini-Mental State
      Examination (MMSE) and the Clinical Dementia Rating (CDR). Diagnosis and type of
      dementia were determined by a neurologist. The cohorts were followed for 5 years,
      and causes of death were determined. Cox proportional hazards model was used for
      survival analyses. Analyses were performed comparing the apoE e4 allele and
      others. RESULTS: At baseline, the apoE e4 allele was found in 148 of 550 subjects
      (27%), in 24% of nondemented persons, in 51% of patients with probable or
      uncertain Alzheimer's disease (AD), and in 34% patients with vascular dementia.
      The CDR score was worse among subjects with an e4 allele compared with others at
      baseline (P < .001) and after a 5-year follow-up (P = .007). The crude mortality
      rates of subjects with and without an e4 allele were 48% (n = 71) and 37% (n =
      148), respectively. After controlling for age and gender, the hazard ratio of an
      e4 allele was 1.61 (95% CI, 1.21-2.14) for all-cause mortality, deaths caused by
      dementia 2.20 (95% CI, 1.03-4.72), and presence of AD 3.24 (95% CI, 1.67-6.25).
      CONCLUSIONS: In a population aged 75 to 85 years, the presence of an apoE e4
      allele is associated with impaired cognitive function, clinical dementia, AD, and
      excess 5-year mortality resulting from dementia and all causes.

PMID- 9625187
TI  - A two-year follow-up of geriatric consults in the emergency department.
AB  - OBJECTIVE: To characterize the population and provide a 2-year follow-up for
      those patients for whom a geriatric consult was requested in the emergency
      department (ED) of an acute care hospital. BACKGROUND: Older people tend to use
      health services, including the ED, disproportionately. This phenomenon has
      implications for medical services as the number of older people continues to
      increase. To our knowledge, long-term follow-up of patients for whom ED geriatric
      consultation was requested has not been described. SETTING: The emergency
      department of a 628-bed tertiary care university hospital in Montreal, Canada.
      SUBJECTS: 326 older patients examined in the ED by a geriatric consult team
      (GCT). METHODS: The records kept by the GCT during a 12-month period were
      reviewed retrospectively, and the patient cohort was followed for 2 years by
      telephone or review of hospital charts. Mortality, rate of revisit to ED,
      readmission to hospital, and final disposition were examined. RESULTS: The study
      revealed a particularly high hospital admission rate (63.5%) among those older
      people consulted by the GCT. The high prevalence rates for the classic geriatric
      syndromes of falls, incontinence, iatrogenic events, and confusional states
      suggest a need to address these problems early in their presentation, preferably
      beginning in the ED. A 2-year follow-up exhibited high mortality rates (33.7%) as
      well as a long-term institutionalization rate of 52%. CONCLUSION: The older
      patients seen in the ED of the acute care hospital for whom multidisciplinary
      geriatric consult is requested constitute a high-risk population. Within 2 years
      after initial consultation, many are dead and more than half have been
      institutionalized. The results of our follow-up imply the need for
      multidisciplinary intervention early on in the course of an older patient's ED
      visit as well as close follow-up after hospital discharge.

PMID- 9625188
TI  - Causes and prognosis of acute renal failure in the very old. Madrid Acute Renal
      Failure Study Group.
AB  - OBJECTIVES: There is a tendency to treat older people with Acute Renal Failure
      (ARF) less aggressively because of the presumed less acceptable end results. This
      has not been proved, and their prognosis may be similar to that found in the
      younger population. There are no studies on the incidence, causes, and evolution
      of ARF in patients 80 years of age and older. DESIGN: A multicenter, prospective,
      longitudinal study. SETTING: The 13 hospitals with nephrology units that serve
      the 4.2 million people in Madrid, Spain. MEASUREMENTS: A number of demographic,
      clinical, and therapeutic variables were studied in each case. RESULTS: One
      hundred three episodes of ARF occurred in patients 80 years of age and older
      (Group 1), 256 in patients aged 65 to 79 years (Group 2), and 389 in people
      younger than age 65 (Group 3). Acute tubular necrosis was diagnosed in 39% of
      cases in Group 1, in 48% in Group 2, and in 55% in Group 3 (P = .004, 1 vs 3);
      prerenal ARF was diagnosed in 30%, 28%, and 21% (P = .054, 1 vs 3) and
      obstructive ARF in 20%, 11%, and 7% (P < .001, 1 vs 3) of cases, respectively.
      Serum creatinine at admission, peak values, values at discharge or death,
      duration of both admission and ARF episode, and mortality were similar in all
      groups. In stratified analysis, relative risk for mortality in patients aged more
      than 80 years was 1.09 [95%CI 0.86,1.36 (P = .562)], and in those aged 65 to 79
      it was 0.99 [95%CI 0.83,1.18 (P = .954)] compared with patients aged less than 65
      years. Risk of death was also similar when only acute tubular necrosis cases were
      considered. Sustained hypotension was associated with higher mortality (44% of
      nonsurviving older persons vs 9% of survivors, P < .001). CONCLUSION: Age is not
      a particularly poor prognostic sign, and outcome seems to be within acceptable
      limits for very old patients with ARF. Acute dialysis should not be withheld from
      patients solely because they are more than 80 years of age.

PMID- 9625189
TI  - Psychometric characteristics of the minimum data set I: confirmatory factor
      analysis.
AB  - OBJECTIVE: To determine the structure and statistical reliability of the
      federally mandated Minimum Data Set (MDS). DESIGN: Confirmatory, hypothesis
      testing factor analysis was performed on MDS protocols of 733 nursing home
      residents. SETTING: All participants were residents of the Philadelphia Geriatric
      Center. PARTICIPANTS: Participants represented consecutively admitted skilled and
      intermediate care residents and another pool of residents with probable dementia.
      MEASUREMENTS: MDS protocols were completed by nurse care coordinators. Item
      composites hypothesized represented the domains of cognition, activities of daily
      living, time use, social quality, depression, and problem behaviors. RESULTS: For
      higher functioning residents (n = 336) and for all residents together, all domain
      clusters except social quality were confirmed. None of the domain clusters were
      confirmed within the more impaired (n = 391) group. CONCLUSIONS: The MDS does
      provide usable indicators of five areas of basic competence of nursing home
      residents. Lack of reliability in rating many aspects of the behavior and states
      of cognitively impaired residents is evident, however. Improvement of such
      measures and rating procedures constitutes a major research priority.

PMID- 9625190
TI  - Psychometric characteristics of the minimum data set II: validity.
AB  - OBJECTIVE: To determine the validity of the Minimum Data Set (MDS). DESIGN: MDS
      domain scores were correlated with a variety of independently obtained measures
      of basic behavioral and mental health functions of 513 nursing home residents.
      SETTING: All participants were residents of the Philadelphia Geriatric Center.
      PARTICIPANTS: One group of residents (n = 260) represented consecutive admissions
      who were able to respond to formal testing. The other group of residents (n =
      253) represented presumably cognitively impaired residents whose data did not
      depend on self-report. MEASUREMENTS: MDS item-composite scores based on a
      confirmatory factor analysis were derived for the domains of cognition,
      activities of daily living (ADL), time use, depression, and problem behaviors.
      Hypotheses stating how these MDS domains should be related to standard measures
      of cognitive function, ADL, depression, agitation, social behavior, and
      irritability were tested. CONCLUSIONS: The majority of the hypotheses were
      upheld, thus suggesting that the MDS is usable as a source of research data. The
      sizes of the validity coefficients were modest, however. Depression and problem
      behavior were less well affirmed than cognition, ADL, and Time Use. There is a
      clear need for improvement in training and probably in the form of MDS
      measurement in some areas.

PMID- 9625191
TI  - Accuracy of medical records in hip fracture.
AB  - OBJECTIVE: To determine the accuracy of diagnoses and procedure codes in medical
      records for hip fracture patients. DESIGN: A validation sample of hip fracture
      medical records was used to compare the facesheet data with progress notes,
      operative reports, and discharge summaries for patients in a prospective study of
      functional recovery. SETTING: Eight Baltimore hospitals with the highest volume
      of older hip fracture patients. PATIENTS: Study subjects were 343 community
      dwelling patients, 65 years of age and older, admitted to one of eight Baltimore
      hospitals between January 1990 and June 1991 with a diagnosis of hip fracture.
      MAIN OUTCOME MEASURES: Facesheet diagnosis codes were compared with admitting
      notes, discharge summary, and/or progress notes. The abstracted surgical
      procedure was compared with postoperative radiographs. RESULTS: Excess coding of
      diagnoses on the hospital facesheet was evident in 12% of charts. In 17% of
      charts, a complication identified in the chart was not coded on the facesheet.
      More complications with low severity were omitted. Agreement between the
      abstractor's procedure review and radiograph readings for arthroplasty was 84%.
      In 15% of patients, the abstractor coded total arthroplasty when hemiarthroplasty
      was done. CONCLUSIONS: Discrepancy between the hospital facesheet and the medical
      record and between the abstracted surgical procedure and radiographs was found
      for hip fracture patients. This may make findings from health outcomes research
      relying on administrative databases uncertain and reimbursement inaccurate.

PMID- 9625192
TI  - Underutilization of angiotensin-converting enzyme inhibitors in older patients
      with Q-wave anterior myocardial infarction in an academic hospital-based
      geriatrics practice.
AB  - OBJECTIVE: To investigate the prevalence of angiotensin-converting enzyme (ACE)
      inhibitors use in older persons without contraindications to ACE inhibitors and
      with prior Q-wave anterior myocardial infarction (MI), anterior MI with
      congestive heart failure (CHF), and with anterior MI and a left ventricular
      ejection fraction (LVEF) < or = 40% in an academic hospital-based geriatrics
      practice. DESIGN: A retrospective analysis of charts from all older patients seen
      from January 1996 through July 1997 at an academic hospital-based geriatrics
      practice was performed to investigate the prevalence of ACE inhibitor use in
      older patients with prior Q-wave anterior MI, anterior MI with CHF, and anterior
      MI with LVEF < or = 40% without contraindications to ACE inhibitors. SETTING: An
      academic hospital-based primary care geriatrics practice staffed by fellows in a
      geriatrics training program and full-time faculty geriatricians. PATIENTS: Ninety
      six women and 65 men, mean age 82 +/- 8 years (range 65 to 96), were included in
      the study. MEASUREMENTS AND RESULTS: Of 161 patients with Q-wave anterior MI and
      no contraindications to ACE inhibitors, LVEF was measured in 58 patients (36%),
      56 (35%) of whom were receiving ACE inhibitors. Of 45 patients with Q-wave
      anterior MI and CHF, 30 patients (67%) were receiving ACE inhibitors. Of 15
      patients with Q-wave anterior MI and asymptomatic LVEF < or = 40%, four patients
      (27%) were receiving ACE inhibitors. CONCLUSIONS: There is a marked
      underutilization of use of ACE inhibitors in treating older patients with Q-wave
      anterior MI in an academic hospital-based geriatrics practice.

PMID- 9625193
TI  - Time and cost for recruiting older adults.
AB  - OBJECTIVES: The purpose of this study was to examine the time requirements and
      costs of recruiting older adults for participation in a medical center
      /university-sponsored, home-based nutrition education study. A two-step
      recruitment strategy consisting of an introductory letter followed by a telephone
      call was used. DESIGN: A random selection of 1300 individuals aged 60 to 74 years
      was drawn from a patient database of a large, rural, tertiary care hospital to
      receive introductory letters and recruitment telephone calls. One week after the
      mailing, potential subjects were contacted by trained interviewers and asked to
      participate in a home-based nutrition education study. PARTICIPANTS: Men and
      women, aged 60 to 74 years, whose names appeared in a rural, tertiary care
      hospital database. MEASUREMENTS: Recruitment rate, time required for recruitment
      by telephone, and cost of the combined mailing and telephone recruitment effort.
      RESULTS: Of the 1300 individuals selected, 1077 (83%) people were contacted by
      phone and 223 (17%) people were unable to be reached. A total of 2895 calling
      attempts were required to determine the recruitment status of those identified as
      potential participants. Of those reached by phone, the recruitment rate was 45%.
      The total cost (mailing, telephone, and database management) per recruited
      subject was $8.56. CONCLUSION: This study has helped to establish the costs of
      recruitment for home-based education interventions using a two-step strategy of
      an introductory mailing and follow-up telephone interview.

PMID- 9625194
TI  - Attention, frailty, and falls: the effect of a manual task on basic mobility.
AB  - OBJECTIVE: To investigate the effect of a second task on balance and gait
      maneuvers used in everyday life. Our hypothesis was that those who were more
      distracted by a familiar manual task performed concurrently with functional
      maneuvers were more frail and more prone to falls. DESIGN: A cross-sectional
      design with prospective follow-up for falls. SETTING: Sheltered accommodation in
      Umea, Sweden. PARTICIPANTS: Forty-two residents (30 women, 12 men; mean age +/-
      SD = 79.7 +/- 6.1 years), ambulant with or without a walking aid, able to follow
      simple instructions and able to carry a tumbler. MEASUREMENTS: Timed Up & Go
      (TUG), i.e., the time taken to rise from an armchair, walk 3 meters, turn round,
      and sit down again. TUG was repeated with an added manual task (TUGmanual), which
      was to carry a glass of water while walking. The Montgomery-Asberg Depression
      Rating Scale, Barthel Index, Functional Reach, Mini-Mental State Examination, and
      Line Bisection test were used to assess for frailty. The subjects were followed
      up prospectively regarding falls indoors for a period of 6-months. RESULTS:
      Subjects with a time difference (diffTUG) between TUGmanual and TUG of > or = 4.5
      seconds were considered to be distracted by the second task. Ten subjects had a
      difference in time of > or = 4.5 seconds. These subjects were more frail, and
      seven of them fell indoors during the follow-up period (odds ratio 4.7,
      95%Confidence Interval (CI) 1.5-14.2). CONCLUSION: The time difference between
      the TUGmanual and the TUG appears to be a valid marker of frailty and a useful
      tool for identifying older persons prone to falling.

PMID- 9625195
TI  - Alzheimer's disease under managed care: implications from Medicare utilization
      and expenditure patterns.
AB  - BACKGROUND: Little information is available about the costs, utilization
      patterns, and the delivery system used by Medicare beneficiaries with chronic
      illnesses. This information will become increasingly important as more Medicare
      beneficiaries with chronic illness enroll in managed care plans and delivery
      systems must be developed to meet their needs. OBJECTIVES: To analyze health care
      expenditures and utilization patterns for Medicare beneficiaries with dementia of
      the Alzheimer type (DAT) and compare them with those of all Medicare
      beneficiaries. DESIGN: A cross-sectional study. SETTING: Practices providing
      services to Medicare beneficiaries in the U.S. SUBJECTS: Aged Medicare
      beneficiaries with DAT in fiscal year (FY) 1992. MEASUREMENTS: Medical
      expenditures and utilization patterns. RESULTS: In FY 1992, per capita Medicare
      expenditures for 9323 patients with DAT were $6208, or 1.9 times the per capita
      expenditure for all 1,221,615 beneficiaries in our sample. Inpatient care
      accounted for 62.7% of expenditures. Internal medicine was the specialty
      identified with the largest proportion of expenditures, but no single specialty
      accounted for the majority of care. Payments increased with comorbid conditions
      such as heart failure, chronic pulmonary diseases, and cerebrovascular disease.
      CONCLUSION: Current Medicare capitation payments to managed care plans may not
      meet the higher expected annual costs of care for beneficiaries with DAT. In
      turn, physicians (or physician groups) who accept capitation for Medicare
      beneficiaries with DAT should also consider how capitation rates are established
      by managed care plans and should learn ways to reduce financial risk.

PMID- 9625196
TI  - Developing rehabilitative behavioral interventions for long-term care: technology
      transfer, acceptance, and maintenance issues.
AB  - Rehabilitative behavioral interventions that are documented in clinical trials to
      improve nursing home resident outcomes and are recommended by practice guidelines
      are often not adapted for daily use in nursing homes and other long-term care
      (LTC) facilities. Failure to evaluate issues other than clinical efficacy when
      developing interventions contributes to this gap between efficacy and
      effectiveness in practice. A potential solution is a research model that
      supplements traditional clinical intervention research with methodology designed
      specifically to evaluate the ability of LTC facilities to implement the
      interventions. This paper discusses several critical issues of intervention and
      implementation that should be addressed, including targeting interventions,
      advocacy, cost-effectiveness, training, and quality control. We also describe how
      clinical trials could be designed and staged to increase the probability that
      effective interventions will be implemented in the day-to-day care of frail older
      patients in LTC facilities.

PMID- 9625197
TI  - Quality of life of older adults with urinary incontinence.

PMID- 9625198
TI  - Alzheimer's disease and managed care: how much will it cost?

PMID- 9625199
TI  - Dementia and the goals of care.

PMID- 9625200
TI  - Emerging antidementia drugs: a preliminary ethical view.
AB  - What ethical concerns regarding the application of new antidementia compounds are
      pertinent to the best interests of patients with Alzheimer's disease and their
      caregivers? Based on collected preliminary anecdotal accounts, these concerns are
      important and should be considered carefully by clinicians, researchers, and
      families.

PMID- 9625201
TI  - Improving health care quality by reimbursement policy.

PMID- 9625202
TI  - Antihypertensive drugs and cognitive function in older people.

PMID- 9625203
TI  - Antihypertensive medications.

PMID- 9625204
TI  - The Yale Geriatric Care Program is not effective in a pilot study in The
      Netherlands.

PMID- 9625205
TI  - Deaths caused by bed rails.

PMID- 9625206
TI  - Stroke: atherosclerosis or arteritis?

PMID- 9625207
TI  - Disease and sleep satisfaction at age 70.

PMID- 9625208
TI  - Social separation, housing relocation, and survival in simian AIDS: a
      retrospective analysis.
AB  - OBJECTIVE: To test the hypothesis that changes in housing, particularly those
      involving social separations, would have a negative impact on survival in rhesus
      monkeys experimentally inoculated with the simian immunodeficiency virus (SIV).
      METHODS: An archival methodology was used. Colony records at four Regional
      Primate Research Centers were screened, and data pertaining to demographics,
      contents of the inoculum, medical history before and after inoculation, and
      housing relocations and social companions were coded. The final sample size
      totaled 298 individuals. RESULTS: Following statistical control of covariates,
      housing relocations and social separations in the 90-day period before SIV
      inoculation and in the 30-day period after inoculation were associated with
      decreased survival. There was evidence that housing disruptions occurring earlier
      after inoculation were associated with shorter survival. Finally, a subset of
      animals was found to have been socially housed after SIV inoculation; such
      experience had negative consequences for survival. CONCLUSIONS: The results
      indicate that psychosocial experiences that likely produce a stressful state are
      associated with shorter survival in SIV-infected monkeys.

PMID- 9625209
TI  - Compelling retrospective results call for creative prospective investigations.

PMID- 9625211
TI  - Psychosocial experiences influence functioning: new risks, new outcomes.

PMID- 9625210
TI  - Psychosocial work characteristics and social support as predictors of SF-36
      health functioning: the Whitehall II study.
AB  - OBJECTIVE: To assess whether work characteristics and social support are
      predictors of physical, psychological, and social functioning. METHOD: Work
      characteristics (Karasek and Siegrist models) and social support at baseline were
      used to predict health functioning measured by the SF-36 General Health Survey 5
      years later in a prospective cohort study of 10,308 British male and female civil
      servants. RESULTS: Effort-reward imbalance and negative aspects of close
      relationships predicted poor physical, psychological, and social functioning
      after adjustment for the potential confounding effects of age, employment grade,
      baseline ill health, and negative affectivity. These psychosocial characteristics
      seem to act in a similar way in the healthy and those with existing illness.
      Psychological demands at work in women, and low confiding/emotional support in
      men, also predicted poor functioning. Etiologically. these effects are not
      mediated through health-related behaviors. CONCLUSIONS: Negative aspects of work
      (high demands and effort-reward imbalance) and negative aspects of close
      relationships are independent powerful predictors of poor health functioning.
      They may have an etiological role, which is independent of baseline illness.

PMID- 9625212
TI  - Presidential address: Gastrointestinal illness and the biopsychosocial model.
AB  - OBJECTIVE: To review the evidence supporting the biopsychosocial model in
      understanding patients with gastrointestinal disorders (GI). METHOD: Essay of
      personal experience and review of related literature through a MEDLINE search.
      RESULTS: Through clinical examples of three common gastrointestinal disorders, a
      case is made to refocus our understanding from a biomedical or disease-based
      model of illness to a biopsychosocial model. With the latter model, the
      psychosocial and biological predeterminants are seen to interact in the clinical
      expression of illness and disease. With gastroesophageal reflux disease, the
      evidence shows that stress can lead to amplification of heartburn symptoms that
      is independent of the degree of reflux. Functional gastrointestinal pain is "an
      illness without disease," where structural or physiological disturbance of the GI
      system does not exist. Rather, the symptoms are understood in terms of visceral
      hypersensitivity as modulated by central nervous system activity. With the
      Crohn's disease example, the clinical expression of the disorder is not explained
      by the degree of disease activity. Rather, the symptoms and impaired quality of
      life relate to preexisting psychosocial determinants. The observed association of
      stress with disease activation in Crohn's disease is explained by stress-related
      alterations in psychoimmunological function via the hypothalamic-pituitary
      adrenal axis. CONCLUSIONS: Gastrointestinal disorders, as a model for other
      medical conditions, exemplify the important role of an integrated,
      biopsychosocial model of illness.

PMID- 9625213
TI  - Improving communication skills--a randomized controlled behaviorally oriented
      intervention study for residents in internal medicine.
AB  - OBJECTIVE: We investigated whether patient-centered communication skills can be
      taught to residents in Internal Medicine by using a time-limited behaviorally
      oriented intervention. METHOD: Residents working at the Department of Internal
      Medicine were randomly assigned to an intervention group (IG; N = 19) or a
      control group (CG; N = 23). In addition to 6 hours of standard medical education
      per week, the IG received specific communication training of 22.5 hours duration
      within a 6-month period. Initially and 10 months later, participants performed
      interviews with simulated patients. Interviews were rated by blinded raters who
      used the Maastricht History and Advice Checklist-Revised. RESULTS: Compared with
      the CG, the IG improved substantially in many specific communication skills. Both
      groups improved in the "amount of medical information identified" and in the
      ability to "communicate about feasibility of treatment." CONCLUSION: Patient
      centered communication skills such as those presented in this intervention study
      can be taught. The ability to gain medical information and the readiness to
      communicate about aspects of medical treatment seem to improve with more
      professional experience; however, they also profit from the intervention.

PMID- 9625214
TI  - Increased psychosocial strain in Lithuanian versus Swedish men: the LiVicordia
      study.
AB  - OBJECTIVE: Coronary heart disease (CHD) mortality is four times higher in 50-year
      old Lithuanian men than in 50-year-old Swedish men. The difference cannot be
      explained by standard risk factors. The objective of this study was to examine
      differences in psychosocial risk factors for CHD in the two countries. METHODS:
      The LiVicordia study is a cross-sectional survey comparing 150 randomly selected
      50-year-old men in each of the two cities: Vilnius, Lithuania, and Linkoping,
      Sweden. As part of the study, a broad range of psychosocial characteristics,
      known to predict CHD, were investigated. RESULTS: In the men from Vilnius
      compared with those from Linkoping, we found a cluster of psychosocial risk
      factors for CHD; higher job strain (p <.01), lower social support at work, lower
      emotional support, and lower social integration (p values <.001). Vilnius men
      also showed lower coping, self-esteem, and sense of coherence (p values < .001),
      higher vital exhaustion, and depression (p values < .001). Quality of life and
      perceived health were lower and expectations of ill health within 5 to 10 years
      were higher in Vilnius men (p values < .001). Correlations between measurements
      on traditional and psychosocial risk factors were few and weak. CONCLUSIONS: The
      Vilnius men, representing the population with a four-fold higher CHD mortality,
      had unfavorable characteristics on a cluster of psychosocial risk factors for CHD
      in comparison with the Linkoping men. We suggest that this finding may provide a
      basis for possible new explanations of the differences in CHD mortality between
      Lithuania and Sweden.

PMID- 9625215
TI  - Circulating lymphocyte subsets in major depression and dysthymia with typical or
      atypical features.
AB  - OBJECTIVE: Inconsistent results have been reported concerning circulating
      lymphocyte subsets in depression. To establish whether the immune alterations in
      depression could be related to neurovegetative symptoms, lymphocyte subsets were
      assessed in major depressive and dysthymic patients who exhibited either typical
      or atypical features (ie, the latter characterized by mood reactivity and
      reversed neurovegetative features). METHOD: Blood was collected from major
      depressive, atypical depressive, typical dysthymic, or atypical dysthymic
      patients and from nondepressed control subjects. Circulating lymphocyte subsets
      (CD3, CD4, CD8, CD19, CD16/CD56) were determined by flow cytometry. In a subset
      of patients, lymphocyte subsets were also determined after a 12-week course of
      antidepressant medication. RESULTS: Although T and B cell populations did not
      differ between the depressive subtypes and control subjects, circulating natural
      killer (NK) cells were elevated in depressive illness, and varied as a function
      of depressive subtype and sex. Among male patients, NK cells were elevated to a
      greater extent in typical than in atypical depression, and more so in major
      depressive than in dysthymic patients. Among female patients, circulating NK
      cells were lower than in male patients, and only among the typical major
      depressive patients did NK cells exceed those of controls. Normalization of NK
      cells occurred with successful pharmacotherapy. CONCLUSIONS: Depression may be
      associated with elevated levels of circulating NK cells. Although the
      neurovegetative features associated with depression, particularly altered eating,
      may have contributed to the elevated NK cells, depressive affect itself also
      contributed in this respect. However, the relative contributions of these factors
      varied between male and female patients.

PMID- 9625216
TI  - Cardiovascular and immune responses to acute psychological stress in young and
      old women: a meta-analysis.
AB  - OBJECTIVE: To describe the relationships between cardiovascular and natural
      killer (NK) cell number changes on acute psychological stress in women. METHOD:
      Data from eight different studies were analyzed. A total of 128 healthy female
      subjects, 85 younger (18-45 years) and 43 older (49-87 years), had been subjected
      to a speech stressor (N = 80) or a mental effort stressor (N = 48), mental
      arithmetic, or the Stroop test. Correlations between changes in NK cell numbers,
      systolic (SBP) and diastolic (DBP) blood pressure, and heart rate (HR) were
      computed. Meta-analysis programs were used to study correlations across studies
      and to examine whether correlations differed with stressors or age. RESULTS: In
      all studies, significant increases over baseline were observed for each variable.
      Across studies, the mean weighted r between changes in HR, DBP, and SBP was
      medium (rw = .25) to large (rw = .64). A medium to large average correlation
      between HR and NK changes (rw = .37) was observed, whereas average correlations
      of changes in NK cell numbers with blood pressure changes were small to medium
      (rw < or = .23). Correlations between changes in NK cell numbers and
      cardiovascular variables were homogeneous across studies, whereas mutual
      correlations between cardiovascular variables were heterogeneous. One moderator
      variable showed itself: correlations between HR and DBP reactions were larger in
      studies with older than younger subjects. CONCLUSION: NK cell changes and HR
      responses induced by acute stress in women are regulated, to some extent, by the
      same mechanisms. Neither the type of stressor nor age seem to be very important
      when considering correlations between NK cell and cardiovascular changes. This
      study integrates information about NK cell and cardiovascular responses in women
      that can be used as reference material in future studies.

PMID- 9625217
TI  - Plasma pyridoxine deficiency is related to increased psychological distress in
      recently bereaved homosexual men.
AB  - OBJECTIVE: Previous research has demonstrated that a theoretical model including
      measures of life stressors, social support, and coping style significantly
      predicts psychological distress. This study tested plasma pyridoxine (vitamin B6)
      deficiency status as a predictor of overall psychological distress and specific
      mood states in this model, controlling for HIV-1 serostatus. METHOD: Subjects
      included HIV-1+ (N = 76) and HIV-1- (N = 58) recently bereaved homosexual men. At
      baseline, subjects completed a battery of psychosocial questionnaires, together
      with a physical examination and venipuncture. The Profile of Mood States (POMS)
      provided measures of overall psychological distress as well as specific mood
      states. Pyridoxine deficiency status (a categorical measure of deficient vs.
      adequate status) was determined with a bioassay of erythrocyte aspartate
      aminotransferase activity. RESULTS: Pyridoxine deficiency was a significant
      predictor of increased overall psychological distress in this model, controlling
      for life stressors, social support, coping style, and HIV-1 serostatus. In post
      hoc analyses of specific mood state effects, pyridoxine deficiency status was
      significantly associated with increases in depressed, fatigued, and confused mood
      levels, but not with those of anxiety, anger, or vigor. DISCUSSION: These
      findings suggest that adequate pyridoxine status may be necessary to avert
      psychological distress in the setting of bereavement. Inasmuch as pyridoxine is a
      cofactor for 5-hydroxytryptophan decarboxylase--an enzyme in the biosynthesis
      pathway of serotonin--serotonin level in the brain is implicated as the mediating
      factor.

PMID- 9625218
TI  - Abuse-related posttraumatic stress disorder and alterations of the hypothalamic
      pituitary-adrenal axis in women with chronic pelvic pain.
AB  - OBJECTIVE: Although numerous organic conditions may cause chronic pelvic pain
      (CPP), diagnostic laparoscopy reveals a normal pelvis in many patients with CPP.
      However, psychological studies yield a high frequency of psychopathology and
      increased prevalences of chronic stress and traumatic life events, ie, sexual and
      physical abuse, in women with CPP, suggesting a relationship between
      posttraumatic stress disorder (PTSD) and CPP. As chronic stress and PTSD have
      been associated with specific alterations of the hypothalamic-pituitary-adrenal
      (HPA) axis, we explored stress history, psychopathology and HPA axis alterations
      in women with CPP. METHOD: We recruited 16 patients with CPP and 14 painfree,
      infertile controls from a general hospital where diagnostic laparoscopy was
      performed. Psychological assessment included standardized interviews on clinical
      symptoms, abuse experiences and major life events as well as psychometric testing
      for PTSD-like symptoms and depression. Endocrinological evaluation involved
      determinations of diurnal salivary cortisol levels and hormonal responses to a
      corticotropin-releasing factor (CRF) stimulation test (100 microg human CRF) and
      a low-dose dexamethasone suppression test (0.5 mg). RESULTS: We observed
      increased prevalences of abuse experiences and PTSD in women with CPP as well as
      a higher total number of major life events, whereas the mean extent of depression
      was within the normal range. With respect to endocrine measures, women with CPP
      demonstrated normal to low diurnal salivary cortisol levels, normal plasma
      adrenocorticotropin (ACTH), but reduced salivary cortisol levels in the CRF
      stimulation test, and an enhanced suppression of salivary cortisol by
      dexamethasone. CONCLUSION: Women with CPP demonstrate HPA axis alterations, that
      partly parallel and partly contrast neuroendocrine correlates of PTSD, but show
      marked similarity to findings in patients with other stress-related bodily
      disorders. These findings suggest that a lack of protective properties of
      cortisol may be of relevance for the development of bodily disorders in
      chronically stressed or traumatized individuals.

PMID- 9625219
TI  - Inverse relationship of urinary cyclic GMP to blood pressure reactivity in the
      CARDIA study: vasodilatory regulation of sympathetic vasoconstriction. Coronary
      Artery Risk Development in Young Adults.
AB  - OBJECTIVE: To determine whether urinary cyclic GMP (cGMP), which mediates the
      actions of the vasodilators nitric oxide and atrial natriuretic factor, is
      inversely related to blood pressure (BP) reactivity. In previous work, we found
      that urinary cGMP was inversely related to diastolic BP, but cGMP levels were
      higher among individuals presumed to have increased adrenergic activity,
      increased reactivity, and increased risk of hypertension (blacks, individuals
      with a family history of hypertension). METHOD: We measured 24-hour urinary cGMP
      levels in a substudy of 529 individuals in the Coronary Artery Risk Development
      in Young Adults (CARDIA) study; the sample was 23 to 35 years of age and
      approximately balanced for race (black/white) and gender. BP reactivity to
      stressors (video game, star-tracing, cold pressor) was tested 3 years earlier.
      Baseline BP was included as a covariate in all analyses. RESULTS: Diastolic BP
      reactivity to cold pressor was inversely related to cGMP excretion (p < .05); the
      relationship was strongest among black women with a family history of
      hypertension (partial r = -.33, p < .01). Systolic BP reactivity to star-tracing
      was also inversely related to cGMP (p < .01); the relationship for both star
      tracing and video game stressors was strongest among black men (partial r values
      = -.25 and -.24, respectively; p values < .01). CONCLUSIONS: The results indicate
      that vasodilatory activity may impact the BP response to stress through
      modulation of adrenergic activation, particularly among blacks.

PMID- 9625220
TI  - Caffeine raises blood pressure at work.
AB  - OBJECTIVE: The study investigated the effects of moderate doses of caffeine on
      ambulatory blood pressure and heart rate during workday activities. METHODS:
      Healthy, nonsmoking, habitual coffee drinkers (N = 21) received daily doses of
      100 mg and 500 mg of caffeine on 2 days in a crossover design. Treatment order
      was random and counterbalanced, and administration was double-blind. Ambulatory
      monitoring was conducted for 6 to 9 hours during normal workday activities and
      diary entries were completed at each measurement. Ambulatory data were analyzed
      for the effects of caffeine dose, controlling for variations in posture, physical
      activity, and perceived stress. RESULTS: The average workday blood pressure and
      heart rate were significantly higher when the higher dose of caffeine was
      consumed. Controlling for other factors, dose-related differences were 4 mm Hg
      for systolic and 3 mm Hg for diastolic blood pressure, and were 3 bpm for heart
      rate. CONCLUSIONS: Results support earlier evidence that caffeine raises blood
      pressure at work, and demonstrate that these pressor effects are independent of
      changes in posture, physical activity, or stress. Daily blood pressure increases
      associated with caffeine consumption could increase the risk of developing
      cardiovascular diseases. In addition, caffeine consumption effects might confound
      ambulatory investigations of the cardiovascular effects of other psychosocial,
      personality, or health-behavior factors.

PMID- 9625221
TI  - Gastrin, cholecystokinin, and somatostatin in a laboratory experiment of patients
      with functional dyspepsia.
AB  - OBJECTIVE: To explore the pattern of gastrointestinal hormonal variations in
      plasma and to relate this to possible pathophysiological mechanisms in functional
      dyspepsia. METHOD: There were 25 patients, 12 men and 13 women, aged 24 to 50
      years, with recurrent functional dyspepsia, compared with community control
      subjects pair-wise, matched for age and sex. The subjects participated in a
      laboratory stress experiment with timed provocations. At fixed intervals, 22
      samples of blood were drawn from each subject and frozen for later peptide
      analyses. Levels of gastrin, cholecystokinin (CCK), and somatostatin were
      measured by radioimmunoassay. Peptide levels were studied during a friendly
      greeting, a stress interview, and a food stimulation. RESULTS: Mean hormone
      values did not differ between the groups. Smokers had lower mean CCK than
      nonsmokers. Patients with a high degree of dyspeptic symptoms during the week
      preceding the experiment had a higher mean somatostatin level than patients with
      a low degree of dyspeptic symptoms. Heartburn correlated positively with the mean
      somatostatin level. Mean gastrin correlated with body mass index. During the 15
      minute stress interview, significant changes in peptide variations were noted:
      Gastrin increased in both patient and control group subjects. CCK levels
      increased in patients from 7.2 pmol/l (6.0-8.5) to 9.8 pmol/l (8.2-11.4), but not
      in control subjects (p < 0.04, two-way interaction). Somatostatin increased
      significantly earlier in patients than in the control subjects during the stress
      interview. CONCLUSIONS: A positive relationship was found between the mean level
      of somatostatin and the degree of dyspeptic symptoms. Gastrin, CCK, and
      somatostatin were all sensitive to an anxiety-provoking interview. CCK and
      somatostatin may possibly link psychological reactions to the pathophysiology of
      functional dyspepsia.

PMID- 9625222
TI  - Nonsurgical factors that influence the outcome of bariatric surgery: a review.
AB  - OBJECTIVE: Severe obesity (ie, at least 100% overweight or body mass index > or
      =40 kg/m2) is associated with significant morbidity and increased mortality. It
      is apparently becoming more common in this country. Conventional weight-loss
      treatments are usually ineffective for severe obesity and bariatric surgery is
      recommended as a treatment option. However, longitudinal data on the long-term
      outcome of bariatric surgery are sparse. Available data indicate that the outcome
      of bariatric surgery, although usually favorable in the short term, is variable
      and weight regain sometimes occurs at 2 years after surgery. The objective of
      this study is to present a review of the outcome of bariatric surgery in three
      areas: weight loss and improvement in health status, changes in eating behavior,
      and psychosocial adjustment. The study will also review how eating behavior,
      energy metabolism, and psychosocial functioning may affect the outcome of
      bariatric surgery. Suggestions for additional research in these areas are made.
      METHOD: Literature review. RESULTS: On average, most patients lose 60% of excess
      weight after gastric bypass and 40% after vertical banded gastroplasty. In about
      30% of patients, weight regain occurs at 18 months to 2 years after surgery.
      Binge eating behavior, which is common among the morbidly obese, may recur after
      surgery and is associated with weight regain. Energy metabolism may affect the
      outcome of bariatric surgery, but it has not been systematically studied in this
      population. Presurgery psychosocial functioning does not seem to affect the
      outcome of surgery, and psychosocial outcome is generally encouraging over the
      short term, but there are reports of poor adjustment after weight loss, including
      alcohol abuse and suicide. CONCLUSIONS: Factors leading to poor outcome of
      bariatric surgery, such as binge eating and lowered energy metabolism, should be
      studied to improve patient selection and outcome. Long-term outcome data on
      psychosocial functioning are lacking. Longitudinal studies to examine the long
      term outcome of bariatric surgery and the prognostic indicators are needed.

PMID- 9625223
TI  - Depression and short REM latency in subjects with chronic fatigue syndrome.
AB  - OBJECTIVE: The hypothesized polysomnographic marker for depression, Rapid Eye
      Movement Latency (REML), was used to investigate two groups of subjects; Chronic
      Fatigue Syndrome (CFS)-not depressed and CFS-depressed. METHOD: CFS subjects were
      classified into depressed and not depressed groups, using the Diagnostic
      Interview Schedule (DIS), and subsequently were studied in a sleep laboratory to
      ascertain REML. RESULTS: Short REML showed a statistically significant
      correlation with the depressed state in CFS subjects. CONCLUSION: Short REM
      latency is associated with depression in the CFS population.

PMID- 9625224
TI  - Relationship of blood coagulation and fibrinolysis to vital exhaustion.
AB  - OBJECTIVE: Acute physical and psychological stressors affect blood coagulation
      and fibrinolysis, but little is known about hemostatic factors associated with
      chronic psychological stress. Prolonged psychological stress may end in a state
      of vital exhaustion, which has been shown to be a risk factor for first
      myocardial infarction and recurrent events after coronary angioplasty. The
      present study tested the hypothesis that vital exhaustion resulting from chronic
      psychological stress is associated with impaired fibrinolytic capacity and
      increased coagulation factors. METHODS: On the basis of a validated questionnaire
      and subsequent structured interview, a well-defined group of otherwise healthy
      exhausted men was recruited (N = 15) and compared with age-matched not-exhausted
      controls (N = 15). Fibrinolytic measures included tissue plasminogen activator
      (TPA) antigen and plasminogen activator inhibitor (PAI-1) activity, and as
      coagulation factors we examined factors VIIc, factor VIIIc, and fibrinogen.
      Control variables were: blood pressure, smoking status, triglycerides,
      cholesterol, and standard hematological measures. Samples were collected twice to
      correct for intraindividual fluctuations. Statistical analyses were performed
      using 2 x 2 mixed model analysis of variance with subsequent univariate testing.
      RESULTS: Vital exhaustion was associated with significantly elevated levels of
      PAI-1 activity (p = .023). The higher PAI-1 activity in exhausted subjects
      (median = 13.0 U/ml vs. 6.0 U/ml) was not accounted for by smoking status or
      serum lipids. No significant differences were observed in TPA antigen, factor
      VIIc, factor VIIIc, and fibrinogen. The groups did not differ in blood pressure,
      smoking status, triglycerides, cholesterol, or standard hematological measures.
      CONCLUSION: These data suggest a reduced fibrinolytic capacity in exhausted
      individuals. Therefore, the relationship between vital exhaustion and risk of
      myocardial infarction may be mediated in part by an imbalance between blood
      coagulation and fibrinolysis.

PMID- 9625225
TI  - Experimental stress and immunological reactivity: a closer look at perceived
      uncontrollability.
AB  - OBJECTIVE: Although stressor uncontrollability has been shown to suppress immune
      responses in animals and for human subjects, the results have been inconsistent.
      We reanalyzed results of our previous study regarding stress-related immune
      deviation in man, to establish whether perceived uncontrollability of an acute
      stressor acts as a co-determinant in the observed changes in immunological
      parameters. METHOD: Three types of cognitive reactions to an acute interpersonal
      stressor were assessed: "motivation," "uncontrollability," and "guiltiness."
      Stress-induced changes in the number of several types of immune cells in
      peripheral blood and proliferative responses of lymphocytes to antigens and
      mitogens were assessed. RESULTS: In comparison with control subjects and with
      subjects perceiving high control over the experimental stress situation, the
      subject perceiving low control showed a stressor-induced decrease in the number
      of T helper cells. Reversely, subjects perceiving high control showed an increase
      in the number of B cells as opposed to the other two groups. The effects of
      perceived uncontrollability could not be accounted for by mood changes, but they
      were related to previously experienced life stress. CONCLUSIONS: Perceived
      uncontrollability of an acute stressor can have immuno-modulating effects over
      and above those of the stressor per se.

PMID- 9625226
TI  - Mucosal wound healing is impaired by examination stress.
AB  - OBJECTIVE: Impairment of wound healing is a well-recognized sequelae of
      conditions that alter immune function, including diabetes, jaundice, and advanced
      age. There is also growing evidence that psychological stress has adverse
      consequences for immune function. This study addressed the effects of a
      commonplace stressor on wound healing. METHOD: Two punch biopsy wounds were
      placed on the hard palate of 11 dental students. The first wound was timed during
      summer vacation, whereas the second was placed on the contralateral side 3 days
      before the first major examination of the term; thus, each student served as her
      or his own control. Two independent methods assessed healing (daily photographs
      and a foaming response to hydrogen peroxide). RESULTS: Students took an average
      of 3 days longer to completely heal the 3.5-mm wound during examinations, ie, 40%
      longer to heal a small, standardized wound. Production of interleukin 1beta (IL
      1beta) messenger RNA (mRNA) declined by 68% during examinations, providing
      evidence of one possible immunological mechanism. These differences were quite
      reliable: No student healed as rapidly or produced as much IL-1beta mRNA during
      examinations as during vacation. CONCLUSIONS: These data suggest that even
      something as transient, predictable, and relatively benign as examination stress
      can have significant consequences for wound healing.

PMID- 9625227
TI  - Posttraumatic stress disorder symptoms after bone marrow transplantation for
      breast cancer.
AB  - OBJECTIVE: On the basis of revisions of DSM criteria, questions have been raised
      concerning the occurrence of posttraumatic stress disorder (PTSD) symptoms among
      adults who have been diagnosed and treated for life-threatening illnesses. The
      present study examined the prevalence and correlates of PTSD symptoms among women
      who had undergone autologous bone marrow transplantation (ABMT) for breast
      cancer. METHODS: Participants were 43 women who had undergone ABMT for breast
      cancer an average of 19 months previously (range = 2 to 62 months) and had no
      clinical evidence of disease at their most recent follow-up visit. PTSD symptoms
      and quality of life were assessed using standardized self-report instruments.
      RESULTS: Between 12% and 19% of participants were likely to meet DSM-IV criteria
      for the current diagnosis of PTSD. Women who were less well educated, had more
      advanced disease at the time of the transplantation and had longer hospital stays
      for the transplantation reported more symptoms of PTSD. Greater PTSD
      symptomatology was associated with reports of poorer physical health, mental
      health, and sleep quality. CONCLUSION: Comparisons with previous research suggest
      that rates of PTSD are higher among women who undergo ABMT as opposed to less
      intensive forms of breast cancer treatment. These findings are consistent with
      the view that development of PTSD symptoms is associated with the degree of life
      threat. The clinical significance of PTSD in this patient population is
      underscored by findings indicating that greater PTSD symptoms are associated with
      poorer health-related quality of life.

PMID- 9625228
TI  - Relation between the longitudinal development of personality characteristics and
      biological and lifestyle risk factors for coronary heart disease.
AB  - OBJECTIVE: This study was undertaken to assess the stability of personality
      characteristics (ie, inadequacy, rigidity, dominance, self-sufficiency, and
      social inadequacy) over a 15-year period covering adolescence and young adulthood
      and to analyze the longitudinal relationships between personality characteristics
      and both biological (ie, lipoproteins, blood pressure, and body fatness) and
      lifestyle (ie, physical activity, dietary intake, smoking, and alcohol
      consumption) risk factors for coronary heart disease (CHD). METHODS: The data
      were derived from the Amsterdam Growth and Health Study, an observational
      longitudinal study in which, over a period from 13 to 27 years of age, six
      repeated measurements were performed on 181 subjects. Both the stability analysis
      and the analysis of the longitudinal relationships were performed by generalized
      estimating equations (GEE). This method is suitable for both continuous and
      dichotomous outcome variables, by using all available longitudinal data. RESULTS:
      Stability coefficients for the personality characteristics varied between 0.39
      for self-sufficiency and dominance and 0.53 for social inadequacy. Self
      sufficiency was inversely related to total serum cholesterol (only male subjects)
      and body fatness; inadequacy was inversely related to systolic blood pressure.
      Dominance (female subjects) was positively related to body fatness and social
      inadequacy (male subjects) was positively related to total serum cholesterol.
      Furthermore, inadequacy was positively related to smoking behavior. Social
      inadequacy and rigidity were inversely related to smoking behavior. Self
      sufficiency was inversely related to alcohol consumption. CONCLUSIONS: Over a
      period of 15 years, personality characteristics showed marginal stability. Weak
      relationships were found between personality characteristics and both biological
      and lifestyle CHD risk factors.

PMID- 9625229
TI  - Psychiatric comorbidity in patients with burning mouth syndrome.
AB  - OBJECTIVE: The goal of this study was to evaluate the prevalence and type of
      psychiatric disorders coexisting with burning mouth syndrome (BMS), to compare
      the clinical features of patients with BMS alone with patients with multiple
      diagnoses, and to investigate the number and severity of life events that occur
      before the onset of BMS. METHOD: There were 102 patients with BMS, with no
      possible local or systemic causes, who were evaluated according to the diagnostic
      criteria of DSM-IV. All axis I diagnoses for which the patients met criteria at
      intake or lifetime were determined. Life events were evaluated for a period of 6
      months before the onset of BMS. A statistical comparison between patients and a
      matched control group was performed first; moreover, patients with BMS alone were
      compared with patients with comorbid BMS. RESULTS: Although 29 (28.4%) BMS
      patients were not given any other lifetime psychiatric diagnosis, high rates of
      comorbid psychiatric diagnoses were found. The most prevalent concurrent
      diagnoses were depressive disorders and generalized anxiety disorder. No
      significant differences emerged in clinical features between patients with and
      without other current psychiatric disorders. The severity of life events, rather
      than in their number, was significantly associated with BMS. CONCLUSIONS: BMS has
      high psychiatric comorbidity but can occur in the absence of psychiatric
      diagnoses.

PMID- 9625230
TI  - Long-term outcome of motor vehicle accident injury.

PMID- 9625231
TI  - Methicillin-resistant Staphylococcus aureus versus the burn patient.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) has become a frequent cause of
      nosocomial infection, its increasing prevalence posing serious therapeutic and
      infection control problems within the hospital environment. MRSA is a major
      challenge to the burn patient, with potential to cause significant morbidity and
      mortality. Burn patients have been shown to become colonised and infected more
      readily than other patient groups. Extensive burn injuries are particularly
      susceptible to infection as a result of the disruption of the normal skin barrier
      and accompanying depression of immune responses. Extended hospitalisation and
      antibiotic therapy have been identified as additional risk factors for MRSA
      carriage and infection. Microbial surveillance, epidemiological studies and the
      introduction of strict infection control regimes can reduce the prevalence of
      MRSA but may be insufficient for eradication or prevention of outbreak
      situations. Recognition of the clinical importance of MRSA to the burn patient
      highlights the need to take appropriate measures to minimise transmission and
      infection in this vulnerable group of patients.

PMID- 9625232
TI  - Fear of MRSA--potential for future disaster.

PMID- 9625233
TI  - Characterization of acellular dermal matrices (ADMs) prepared by two different
      methods.
AB  - The efficacy of acellular dermal matrix (ADM) in the treatment of full-thickness
      skin injuries as a dermal substitute depends on its low antigenicity, capacity
      for rapid vascularization, and stability as a dermal template. These properties
      will be determined largely by the final composition of the ADM. We have treated
      human skin with either Dispase followed by Triton X-100 detergent or NaCl
      followed by SDS detergent, cryosectioned the resulting ADMs, and then
      characterized them immunohistochemically. Staining for cell-associated antigens
      (HLA-ABC, HLA-DR, vimentin, desmin, talin), extracellular matrix components
      (chondroitin sulfate, fibronectin, laminin, vitronectin, hyaluronic acid),
      elastin, and collagen type VII was dramatically reduced or absent from ADMs
      prepared by both methods. However, significant amounts of elastin, keratan
      sulfate, laminin, and collagen types III and IV were still observed in both ADMs.
      Both methods of ADM preparation resulted in extensive extraction of both cellular
      and extracellular components of the skin but retention of the basic dermal
      architecture. In general, ADM prepared by the NaCl-SDS method retained larger
      amounts of each antigen than did that prepared by the Dispase-Triton method. This
      was most evident for laminin and type VII collagen but larger amounts of type IV
      collagen, fibronectin, desmin, elastin, and HLA-DR were also evident in the NaCl
      SDS ADM.

PMID- 9625234
TI  - Superoxide dismutase (SOD) for mustard gas burns.
AB  - Mustard gas (MS) has been used in chemical warfare since World War I. The
      blistering skin lesions are slow to heal. Secondary inflammation might occur, as
      well as damage to organs distant from the original wound. Presently there is no
      specific antidote for burns and poisoning by MS. This study examined treatment
      modalities with free oxygen radical scavengers, copper-zinc, and manganese
      superoxide dismutase (SOD), for MS skin burns in an experimental guinea pig
      model. Each of the SOD compounds reduced dramatically burn lesion area when
      administered intraperitoneally/intralesionally (i.p./i.l.) before wound
      infliction. The protective action of the SODs was also evident in the
      significantly higher histopathological score of biopsies obtained on day 7 from
      local tissue, caused with the lower dose of MS. When the SOD compounds were
      administered i.p. 1 hour after burn infliction, and repeated daily for 7 days, no
      protective effect could be detected under the present experimental conditions.

PMID- 9625235
TI  - Granulocyte-colony stimulating factor improves suppressed neutrophilic
      phagocytosis against hypernatremic condition.
AB  - Phagocytic activity is an important function of neutrophils in the host defense
      against burn wound infection. In a previous report we demonstrated hypernatremic
      suppression of neutrophils at sodium concentrations comparable to these in the
      zone of stasis in the burn wound. At this site the osmotic pressure will be
      elevated as a result of several factors, especially to increased water loss from
      the burn wound surface. In this study the effect of granulocyte-colony
      stimulating factor (G-CSF) on phagocytic activity of human neutrophils against
      hypernatremic suppression is investigated in vitro. In the G-CSF group 150 ng of
      G-CSF was added to four blood samples (5 ml each). Phagocytic activities of the
      control group (n = 10) showed 88.3+/-4.1 per cent (means+/-SD) at 140 mmol/l of
      sodium concentration, 68.2+/-6.9 at 180, 57.6+/-10.1 at 220, and 48.6+/-8.6 at
      260 mmol/l. The G-CSF group showed 88.2+/-7.0 at 140, 79.9+/-9.4 at 180, 71.4+/
      7.4 at 220, and 56.5+/-14.1 at 260 mmol/l. At 180 and 220 mmol/l significant
      differences were recognized. Results of this study suggest a favourable effect of
      G-CSF on suppressed neutrophils under the hypernatremic conditions.

PMID- 9625236
TI  - Risk factors for childhood burn injuries: a case-control study from Greece.
AB  - During a 12-month period 239 children who presented with a burn injury at the
      Emergency Department of a teaching children's hospital in Athens, with city-wide
      coverage, and 239 gender- and age-matched controls with minor non-injury ailments
      were interviewed. The questionnaire covered sociodemographic characteristics of
      the children and their families, information allowing the construction of a burn
      avoidance index in their homes and items from the Achenback scale that were
      synthesized into a child activity score. The data were analyzed through
      conditional logistic regression. In general, socio-demographic variables were not
      of overwhelming importance, although some of the findings indicate that
      supervision lapses and barefoot walking of gypsy children increase the risk of
      burn injuries. The kitchen in an inherently high risk place for injuries and the
      powerful inverse association of the burn avoidance index with burn injury risk
      points towards steps that could be easily taken and impart substantial
      protection. There was no evidence in this study of burn injury proneness or that
      hyperactivity of the child increased the risk of burn injury; indeed, the results
      point in the opposite direction. Our results strongly support the view that
      childhood burn injuries are largely environmentally conditioned and, accordingly,
      easily preventable.

PMID- 9625237
TI  - A 3 year prospective audit of burns patients treated at the Western Regional
      Hospital of Nepal.
AB  - Burns in Nepal cause an estimated 1700 deaths per year and much suffering. We
      carried out a prospective 3 year audit of 237 burns patients admitted to the
      Western Regional Hospital in Pokhara. The aims were to assess the profile of
      burns injuries and what could be achieved in local conditions to guide colleagues
      in developing countries with limited medical facilities. The majority of burns
      occurred at home and were largely preventable. 61 per cent of patients were
      children under 15 years of age. There were more female patients and females had
      more severe burns. No patients with greater than 40 per cent body surface area
      burns of any age group survived. Public education on burns prevention is needed
      but poverty, ignorance and a fatalistic attitude are difficult underlying causes
      to change.

PMID- 9625238
TI  - Epidemiology of elderly patients' burns in the South West of France.
AB  - A retrospective study of 716 patients aged 60 years and above (324 men, 392
      women) was undertaken in order to determine quality control in burns management
      in the South West of France. The following epidemiological data was obtained:
      high hospitalization rate (7 per cent of the general admissions); monthly and
      seasonal periodicity; predominance of indoor accidents (86 per cent) with
      domestic accidents being more frequent in women (63 vs. 37 per cent). Outdoor
      accidents were mainly recreational and were five times more frequent in men than
      in women. The overall mortality was 39 per cent and was influenced by the burns
      extent, depth, predisposing factors and early management. More burns occurred in
      urban areas (53 per cent) but mortality was higher in patients from rural areas
      (62 vs. 38 per cent). It was observed that delay in management, especially fluid
      resuscitation of patients from the rural areas, was partly responsible for this
      outcome. Propositions were made to diffuse more information on the importance of
      early management of burns in rural areas.

PMID- 9625239
TI  - The epidemiology of burns in secondary care, in a population of 2.6 million
      people.
AB  - The numbers of residents of the four counties in the west of Anglia and Oxford
      Region (UK) who were treated for burns (including scalds) in accident and
      emergency (A&E) departments or admitted to hospital in 1994-95 were obtained from
      A&E departments and district health authority records. Burns comprised about 1
      per cent of the workload in the A&E departments. Using the data from district
      health authorities, the rate of admission with a main diagnosis of burns to any
      hospital was 0.14 per thousand population per year. Children under five had the
      highest rate of admission. Approximately half the patients admitted to hospital
      with burns were admitted to burns units, a quarter to plastic surgery wards and
      the rest to different specialties including trauma and orthopaedics, paediatrics,
      and ophthalmology. The median length of stay was 6 days for burns units and 3
      days for plastic surgery units.

PMID- 9625240
TI  - A study of suicide and attempted suicide by self-immolation in an Irish
      psychiatric population: an increasing problem.
AB  - In the Western World self-immolation is an uncommon but dramatic method of
      attempting suicide. In-patients who attempt suicide by fire-setting tend to be
      female with severe psychopathology. In a previous study from the South of
      Ireland, seven cases from a psychiatric and prison population were identified in
      a five year period from 1984 to 1989. This would represent an annual rate of 1.07
      per cent of burns treated in the burns unit at Cork University Hospital. In this
      study 12 cases were identified for the years 1994 and 1995. This represents an
      increase of 3.5 per cent from 1.07 to 4.6 per cent of all burns treated at the
      same institution. Ten of these patients had a previous psychiatric history and
      eight of them were resident on a psychiatric ward when they committed the act.
      Seven of the patients were found to have a high degree of suicide intent of whom
      four died of their injuries, which gives a mortality rate for this group of 33
      per cent. Effective prevention policies are necessary if this increasing problem
      is to be curtailed.

PMID- 9625241
TI  - Suicide by burning: a retrospective review of the Akron Regional Burn Center.
AB  - At the Akron Regional Burn Center from January 1978 through March 1995, 36 cases
      of attempted suicide by burning were identified in 34 patients. The overall
      incidence rate was 1 per cent of all burn center admissions to this institution.
      Of these patients, 21 of 34 were male and 13 of 34 were female. There were 10 of
      34 lethal cases. A high incidence of prior psychiatric illness was identified. In
      all, 22 of 34 patients had a prior psychiatric diagnosis. Depression was the most
      common psychiatric diagnosis by history. The method most commonly used was a
      flame with the addition of a flammable liquid. These results are presented,
      discussed and compared to a review of the literature on the topic.

PMID- 9625242
TI  - Burn mortality in Chandigarh zone: 25 years autopsy experience from a tertiary
      care hospital of India.
AB  - An analysis of autopsy records of burn victims revealed that most burn deaths
      occurred in the age group 21-40 years (67 per cent) with female preponderance (61
      per cent) in all age groups except in the extreme age groups. 62 per cent of burn
      cases originated in urban areas. The majority of subjects (99 per cent females
      and 76 per cent males) died as a result of flame burns. Kerosene was the most
      common factor (76 per cent) in burn deaths. 11 per cent of deaths were due to the
      stove bursting and 27 per cent of victims died due to leakage of oil from the
      stove. 39 per cent of subjects sustained burns when their clothes caught fire.
      Scalds (3.3 per cent), electrical (4.7 per cent) and chemical (2.3 per cent)
      burns were more commonly seen in males, mainly sustained at their working place.
      Accidental burns were observed in 80 per cent of subjects followed by suicidal
      (16.2 per cent) and homicidal burn assaults (4.1 per cent). Peak incidence of
      burns in females was observed between 5.01 a.m. and 11 a.m. (38 per cent), which
      was the time of least incidence in males (10.3 per cent). The opposite trend was
      seen between 11.01 p.m. and 5 a.m. Among males, burn deaths were more common (85
      per cent) in those who were living alone, away from their families; whereas in
      women the incidence of burn deaths was higher (74 per cent) in those living with
      their families. The majority of deaths due to burns occurred within one week (77
      per cent) of the incident. Septicaemia was the major cause of death (55 per
      cent).

PMID- 9625243
TI  - A prospective randomised clinical and histological study of superficial burn
      wound healing with honey and silver sulfadiazine.
AB  - Histological and clinical studies of wound healing have been made on comparable
      fresh partial thickness burns with honey dressing or silver sulfadiazine (SSD) in
      two groups of 25 randomly allocated patients. Of the wounds treated with honey 84
      per cent showed satisfactory epithelialization by the 7th day, and in 100 per
      cent of the patients by the 21st day. In wounds treated with silver sulfadiazine,
      epithelialization occurred by the 7th day in 72 per cent of the patients and in
      84 per cent of patients by 21 days. Histological evidence of reparative activity
      was seen in 80 per cent of wounds treated with the honey dressing by the 7th day
      with minimal inflammation. Fifty two per cent of the silver sulfadiazine treated
      wounds showed reparative activity with inflammatory changes by the 7th day.
      Reparative activity reached 100 per cent by 21 days with the honey dressing and
      84 per cent with SSD. Thus in honey dressed wounds, early subsidence of acute
      inflammatory changes, better control of infection and quicker wound healing was
      observed while in the SSD treated wounds sustained inflammatory reaction was
      noted even on epithelialization.

PMID- 9625244
TI  - Successful recovery of 14 patients afflicted with full-thickness burns for more
      than 70 per cent body surface area.
AB  - Fourteen cases suffering full-thickness burns of more than 70 per cent total body
      surface area (TBSA) have been successfully treated during the last 8 years (1988
      1995). Among these patients, 10 cases suffered from burns of more than 90 per
      cent TBSA. Five cases had full-thickness burns of 80-90 per cent TBSA.
      Escharectomy, followed by coverage of wounds with a homograft to the lower
      surface of which, adjacent to the wound bed, microautoskin grafts had been
      attached was employed to close wounds in the early stages after burn. The
      remaining non-surgically treated wound was treated by exposure and topical silver
      sulfadiazine. The temperature and humidity of the ward was controlled by air
      conditioning and dehumidification. Aggressive excision of eschar and auto
      skingrafting was carried out 3 weeks post-injury. Strictly limiting the uncovered
      wound to less than 5 per cent appeared to be the major effective measure in
      preventing burn infection.

PMID- 9625245
TI  - Early nonsurgical removal of chemically injured tissue enhances wound healing in
      partial thickness burns.
AB  - Chemical burns are slow healing injuries and their depth is difficult to assess.
      Tissue destruction continues as long as active material is present in the wound
      site. The routine therapy for treatment of full thickness chemical burns is early
      excision; it shortens hospitalization and reduces morbidity. However, presently
      there is no specific treatment for chemical burns of partial thickness. This
      study examined several treatment modalities for partial thickness chemical burns:
      surgical excision; laser ablation and chemical debridement with Debridase or
      trypsin-linked to gauze. Chemical burns were inflicted with nitrogen mustard (NM 
      - a nitrogen analog to sulfur mustard -- mustard gas) in an experimental guinea
      pig model. Debridase was most effective and reduced significantly lesion area of
      burns after 'humid' exposure to 2 mg NM. The healing action of Debridase was also
      evident in the significantly higher histopathological score of biopsies from
      local tissue obtained on day 5. Laser ablation was most effective and accelerated
      healing of burn lesions after 'dry' exposure to 5 mg NM. The histopathology score
      of the laser treated burns was higher on day 4 compared to untreated controls. It
      is concluded that for partial thickness chemical burns early nonsurgical removal
      of the damaged tissues accelerates wound healing.

PMID- 9625246
TI  - Scorched eyelashes--do we treat them right?
AB  - Scorched eyelashes and burned eyelids are a common finding in facial burns,
      though the eye itself is often spared. Affected patients often complain of
      foreign body sensation and ocular discomfort in the absence of objective physical
      findings, other than scorched eyelashes and burned eyelash particles in the
      conjunctival sacs. This study was designed to evaluate the efficacy of
      prophylactic trimming of scorched eyelashes as a treatment for these findings and
      complaints. Eleven consecutive facial burn patients with bilateral eyelash
      scorching and no accompanying ocular damage were included. The eyelashes of one
      eye were trimmed, and those of the fellow eye served as untreated controls.
      Ophthalmic examinations were performed and eye-related complaints noted every
      other day for 10 days. We found that symptoms of foreign body sensation and
      discomfort occurred at a lower rate in the treated eyes (P<0.002) and no scorched
      eyelash particles were found in their conjunctival sacs (P<0.004) as compared to
      the untrimmed side. Conjunctival hyperemia was reduced. We suggest that shedding
      of scorched eyelash particles is a major cause of the ocular complaints in facial
      burn patients. Trimming the eyelash affords a simple and effective method of
      prophylactic treatment.

PMID- 9625247
TI  - A retrospective analysis of early excision and skin grafting from 1993-1995.
AB  - Early excision and skin grafting (EEG) is an established and accepted procedure
      for deep burn management. This is a retrospective analysis of 100 patients
      treated with early excision and grafting in burns of all types and up to 65 per
      cent TBSA. Excisional surgery was performed in the period from day 2 to day 7
      post-burn in patients who did not have significant infection (<10(5)) in one to
      two stages. The average mortality rate in all age groups and including smoke
      inhalation injury in our unit was 43.4 per cent. The mortality in the operated
      group was 10.2 per cent. The main causes of mortality were smoke inhalation
      injury, septicaemia (probably originating from the non-excised tissue) and
      extensive burn injury. The functional and aesthetic outcome in EEG patients was
      far superior in comparison with the conventional method of treatment.

PMID- 9625249
TI  - Recent references.

PMID- 9625248
TI  - Toxic epidermal necrolysis in a burn patient complicated by acute pancreatitis.
AB  - This report concerns a previously healthy patient who presented with 8% total
      body surface area burn wounds to his face and neck. Even though his burn wounds
      healed quickly, his course was complicated by the development of toxic epidermal
      necrolysis affecting 60% total body surface area due to a drug reaction. During
      the recovery period he subsequently developed jaundice and pancreatitis -- a rare
      and interesting course that is not well described in the literature.

PMID- 9625250
TI  - Epstein-Barr virus vectors for the treatment of Epstein-Barr virus-associated
      cancers.

PMID- 9625251
TI  - Broadened clinical utility of gene gun-mediated, granulocyte-macrophage colony
      stimulating factor cDNA-based tumor cell vaccines as demonstrated with a mouse
      myeloma model.
AB  - Effective immunization against the murine B16 melanoma by a nonviral approach in
      which a gene gun is used to transfer GM-CSF cDNA into tumor cells has been
      described. We have extended this nonviral approach by using the poorly
      immunogenic murine myeloma MPC11 model. Vaccination with the transfected, GM-CSF
      expressing MPC11 cells induced a potent antitumor cytotoxic T lymphocyte response
      associated with tumor rejection in the majority of the test mice. Furthermore,
      nearly 100% (27 of 28) of the tumor-free mice were able to reject a tumor
      rechallenge. While this approach is clinically attractive because of minimal
      tissue manipulation/culturing and the absence of infectious agents, a number of
      tested human primary tumors, including myeloma cells, have failed to produce high
      levels of GM-CSF after gene gun transfection. To circumvent the low transfection
      efficiency in certain human tumor cells, we showed that combining irradiated
      tumor cells to provide tumor antigens together with gene gun-transfected
      fibroblasts to provide GM-CSF induced effective tumor rejection. We also report
      that normal human skin fibroblasts transfected by the gene gun produce high
      levels of human GM-CSF (250 ng/10(6) cells/24 hr). These results suggest that
      combining irradiated tumor cells with gene gun-transfected fibroblasts results in
      antitumor immune responses and may allow for a wider application of this approach
      to cancer immunotherapy.

PMID- 9625252
TI  - Gene therapy strategies for treating Epstein-Barr virus-associated lymphomas:
      comparison of two different Epstein-Barr virus-based vectors.
AB  - B cell lymphomas in immunocompromised patients frequently contain the Epstein
      Barr virus (EBV) genome (MacMahon et al, 1991), suggesting that gene therapy
      strategies that target EBV-positive cells for destruction might be useful for the
      therapy of such tumors. We have previously shown that stable expression of the
      cytosine deaminase (CD) gene in EBV-positive lymphoblastoid cell lines induces
      cell killing in the presence of the prodrug 5-fluorocytosine, with a substantial
      bystander killing effect (Rogers et al., 1996). To promote specific killing of
      EBV-positive tumor cells, we have constructed two different EBV-based vectors
      containing the cytosine deaminase gene. The first vector (OriP-CD), which
      contains the intact EBV oriP enhancer/replication element, replicates as an
      episome specifically in EBV-positive cells and likewise enhances transcription in
      an EBV-specific manner. The OriP-CD vector cannot be packaged or spread from cell
      to cell. The second vector (OriLyt-CD) contains the EBV lytic origin of
      replication (oriLyt), the EBV packaging sequences (located in the viral termini),
      the oriP enhancer element (but not the complete replication origin), and the EBV
      BZLF1 gene (which induces expression of the EBV proteins required for replication
      of oriLyt). The OriLyt-CD vector is replicated through the oriLyt origin
      specifically in EBV-positive cells and packaged as an EBV pseudovirion. The
      packaged oriLyt-CD virion can subsequently infect cells containing the EBV
      receptor, CD21, and initiate another round of replication in EBV-positive cells.
      Here we demonstrate that each of these two different EBV-based gene therapy
      strategies induces specific killing of EBV-positive B cells in vitro (in the
      presence of 5-FC). The advantages and disadvantages of each strategy are
      discussed.

PMID- 9625253
TI  - Toxin gene-mediated growth inhibition of lung adenocarcinoma in an animal model
      of pleural malignancy.
AB  - Transduction of malignant cells with toxin genes provides a novel strategy by
      which to promote tumor cell destruction. Whereas the capacity of the toxin
      gene/prodrug combination cytosine deaminase/fluorocytosine to inhibit growth of
      human metastatic pulmonary adenocarcinoma cell lines in vitro is established, the
      in vivo efficacy of this binary system has not yet been determined. For the
      development of toxin gene therapy for the treatment of lung adenocarcinoma
      metastatic to the pleural space, a reliable, disease-specific model is required.
      The serosa of the rat small intestine resembles the basal lamina of the pleura
      and provides the basis for a more convenient model than direct injection of tumor
      into the pleural space. Adenocarcinoma cells are inoculated into everted denuded
      rat intestine configured as a sac. Immunocytochemical and histological analyses
      show rapid cell growth with characteristics that mimic nodular metastatic
      intrapleural disease. In the context of this model, systemically delivered
      fluorocytosine significantly inhibits the growth of cytosine deaminase-expressing
      human lung adenocarcinoma cells. The dosing schedule required 30 days; neither
      addition of an enzyme inhibitor that increases the half-life of fluorocytosine
      nor intralumenal drug delivery is effective in shortening (to 15 days) the
      protocol. We conclude that CD continues to hold promise as a toxin gene for lung
      adenocarcinoma gene therapy, and that prolonged prodrug administration may be
      required for maximum efficacy.

PMID- 9625254
TI  - Murine bone marrow expressing the neomycin resistance gene has no competitive
      disadvantage assessed in vivo.
AB  - The neomycin phosphotransferase (neo) gene is one of the most common marker genes
      used in gene transfer experimentation, but potential effects of neo gene
      expression in vivo have not been systematically investigated. Several early
      clinical retroviral gene transfer studies have suggested that neo gene expression
      could have deleterious effects on hematopoiesis, owing to a discrepancy between
      the level of neo-marked transduced marrow progenitor cells compared with mature
      circulating progeny cells posttransplantation (Brenner et al., 1993; Kohn et al.,
      1995; Brenner, 1996b). We examined the long-term in vivo repopulating ability of
      bone marrow from transgenic mice expressing neo from a strong constitutive
      promoter using a competitive repopulation assay. Different ratios of neo
      transgenic and wild-type congenic marrow cells were cotransplanted into W/Wv
      recipient mice. The percentages of blood cells containing the neo transgene in
      each group of recipient mice monitored for 4 months posttransplantation closely
      matched the input ratios of neo transgenic to congenic control marrow cells.
      Similar concordances of engraftment with input ratios of neo transgenic cells
      were also found in spleen, thymus, and whole marrow of recipient mice at 4 months
      posttransplantation. Analysis of the beta-hemoglobin phenotype (beta(single) for
      the neo transgenic and C57 control cells and beta(diffuse) for the congenic
      competitor HW80 cells) in recipients confirmed erythroid repopulation from neo
      transgenic marrow cells at levels matching the input ratios. We conclude that
      hematopoietic cells expressing neo had no engraftment or maturation defects
      detectable in vivo. These results suggest that the low-level contribution of
      vector-marked cells to circulating populations in clinical trials is not due to
      direct deleterious effects of neo gene expression on hematopoiesis.

PMID- 9625255
TI  - Biosafety monitoring of patients receiving intracerebral injections of murine
      retroviral vector producer cells.
AB  - Patients with recurrent malignant brain cancer, who were receiving gene therapy
      by intracerebral injection of murine retroviral vector producer cells (VPCs),
      were monitored for the presence of replication-competent retrovirus (RCR). RCR
      sequences were not detected by polymerase chain reaction (PCR) in any of the 608
      peripheral blood leukocyte (PBL) samples analyzed. Vector DNA sequences were
      detected transiently in PBL samples from a subset of 34 patients. Humoral immune
      responses to a retroviral core protein p30 and murine VPC were detected in some
      patients, most frequently in patients receiving repeated administrations of VPC.
      RCR was not detected in biological assays of PBLs from 41 patients who had either
      anti-retroviral antibodies in sera and/or vector DNA in PBLs. Our data suggest
      that in situ generation of RCR was not detected following intracerebral
      inoculation of VPCs in any of the 128 patients evaluated.

PMID- 9625256
TI  - Quantitation of host cell DNA contaminate in pharmaceutical-grade plasmid DNA
      using competitive polymerase chain reaction and enzyme-linked immunosorbent
      assay.
AB  - The rising interest in gene therapy for the treatment of numerous disorders
      necessitates the need for the large-scale production of therapeutic
      biopharmaceuticals that meet stringent purity standards. Residual host cell DNA
      in recombinant pharmaceuticals has been identified as a potential risk factor
      that must be quantitated carefully both during the manufacturing process and in
      the final product. We describe a PCR method to quantitate contaminating levels of
      host cell DNA in clinical plasmid DNA preparations intended for human gene
      therapy. The quantitation is based on the coamplification of two similar
      templates, the target DNA and a synthetic competitor, and the quantitation of the
      resulting PCR products. The competitor is identical to the target DNA PCR product
      except for a 29-bp internal replacement. As a result, the two PCR products can
      easily be distinguished from each other. The competitive nature of the assay
      allows the use of the ratio of the target DNA PCR product to the competitor DNA
      PCR product to determine the original amount of target DNA in a sample. The
      primers used in this assay anneal to a conserved region of the E. coli 23S rRNA
      gene. One of the primers is biotinylated, allowing the PCR products to be
      detected colorimetrically after their capture on microtiter plates. The capture
      is accomplished by differential hybridization to target and competitor-specific
      probes covalently attached to wells of microtiter plates. The entire assay is
      performed in less than 2 hr postamplification. This method represents an
      attractive alternative to Southern blot analysis, which is the currently
      established method for DNA quantitation.

PMID- 9625257
TI  - Selective and rapid uptake of adeno-associated virus type 2 in brain.
AB  - Recombinant adeno-associated virus (AAV) vectors effectively transfer and express
      foreign genes in the brain. The transferred genes, however, are selectively
      expressed in neurons, and the cause of this specificity is not understood. To
      address this question, wild-type AAV-2 capsids were covalently labeled with the
      fluorophore, Cy3, and infused into the inferior colliculus or the hippocampus.
      Using antibodies to identify neurons (NeuN), astrocytes (GFAP), or
      oligodendrocytes (OX-42), clear neuron-specific uptake of the virus was observed
      as early as 6 min after the start of the infusion. By 30 min postinfusion, AAV
      particles were present in the nucleus of neurons, yet in both the inferior
      colliculus and hippocampus, a subset of neurons did not take up the virus
      particles. No AAV particles were found in astrocytes 1.5 min or 24 hr after virus
      infusion. Interestingly, 1 hr postinfusion, no AAV particles were found in
      microglia, yet by 24 hr postinfusion, a punctate pattern of AAV particles was
      found in microglia. To test whether virus uptake correlated with vector
      transduced cells, an rAAV-CMV-GFP virus was infused. By 3 days postinfusion, GFP
      was localized to neuronal populations with no expression in astrocytes or
      microglia, similar to that of fluorescent virus uptake. These findings
      demonstrate that in brain, AAV particles rapidly bind and enter primarily neurons
      with a pattern similar to that of in vivo vector transduction. In addition, these
      studies indicate that viral binding and uptake, independent of promoter tropism,
      can explain the specificity of AAV brain transduction. Thus, this first
      description of AAV kinetic disposition in vivo should facilitate targeted
      application of this vector for human brain gene therapy.

PMID- 9625258
TI  - Long-term expression of human clotting factor IX from retrovirally transduced
      primary human keratinocytes in vivo.
AB  - A persistent obstacle that has hampered gene transfer experiments is the short
      term nature of transgene expression in vivo. In this article we present evidence
      for sustained expression from primary human keratinocytes, using the retroviral
      vector MFG. Primary keratinocytes were transduced in culture with the MFG
      retroviral vector containing the coding region from factor IX cDNA. Transduced
      keratinocytes, which secreted on average 830 ng of factor IX/10(6) cells/24 hr in
      tissue culture, were used to form a bilayered skin equivalent and grafted onto
      nude mice under a silicone transplantation chamber. Between 0.1 and 2.75 ng of
      human factor IX per milliliter was found in mouse plasma for more than 1 year,
      suggesting that keratinocyte stem cells were both transduced and grafted. The
      results show, for the first time, that long-term expression is obtainable in
      retrovirally transduced keratinocytes after transplantation.

PMID- 9625259
TI  - Targeted transduction of CD34+ cells by transdominant negative Rev-expressing
      retrovirus yields partial anti-HIV protection of progeny macrophages.
AB  - Congenitally acquired HIV infection may be uniquely suited to treatment via
      genetic engineering of CD34+ hematopoietic stem/progenitor cells. However,
      current technologies yield only a small percentage of mature cells that carry the
      inserted genes, and expression is frequently suppressed. Since clinical trials
      employing these methodologies have been proposed for anti-HIV gene therapy of HIV
      infected children, we wished to assess, by in vitro modeling, the expected limits
      of transduction efficiency, expression, and antiviral activity using currently
      available methods. We measured retrovirus-mediated transduction in cord blood
      progenitors and their in vitro-derived progeny macrophages by Mo-MuLV vectors
      expressing a transdominant negative Rev (RevTD). CFU-GM transduction efficiency
      ranged from 7 to 85%, with an average of 28%. Semiquantitative DNA PCR
      demonstrated < or =100 vector sequence copies per 1000 cells in
      monocyte/macrophage cultures, which were grown without selection to better model
      in vivo conditions. When challenged with the macrophagetropic HIV-1BaL isolate,
      cultured macrophages from mock-transduced CFU-GM colonies supported infection in
      eight of eight experimental cultures, control LXSN-transduced progenitors
      supported infection in six of eight cultures, while macrophages derived from
      RevTD-transduced CFU-GM colonies supported infection in four of eight cultures.
      Although these results support the ability of neo(r) retroviral vectors
      containing RevTD to inhibit HIV replication, they indicate that further
      optimization of transduction efficiency and sustained expression will be required
      for effective anti-HIV protection in vivo.

PMID- 9625260
TI  - A method of limited replication for the efficient in vivo delivery of adenovirus
      to cancer cells.
AB  - Replication-deficient viral vectors are currently being used in gene transfer
      strategies to treat cancer cells. Unfortunately, viruses are limited in their
      ability to diffuse through tissue. This makes it virtually impossible to infect
      the majority of tumor cells in vivo and results in inadequate gene transfer. This
      problem can be addressed by allowing limited viral replication. Limited viral
      replication facilitates greater penetration of virions into tissue and can
      improve gene transfer. We have developed a strategy of limited viral replication
      using AdRSVlaclys, a chemically modified E1-deleted adenovirus, to codeliver an
      exogenous plasmid encoding the adenovirus E1 region. This system allows one round
      of viral replication. We examined the effect of this limited adenovirus
      replication in vitro and in vivo. In culture, codelivery of virus and pE1
      resulted in a large increase in infected cells when compared with control cells
      exposed to virus and pUC19. In experiments on nude mice bearing HeLa ascites
      tumors, intraperitoneal injection of AdRSVlaclys/pE1 resulted in a significantly
      higher percentage of infected HeLa cells as compared with the PBS controls (p <
      0.05) or the AdRSVlaclys/pUC19 controls (p < 0.01). These data demonstrate that
      the transcomplementation of replication-deficient adenovirus with exogenous E1
      DNA leads to limited replication, and this controlled replication enhances gene
      transfer efficiency of adenovirus in vivo.

PMID- 9625261
TI  - Adenovirus-mediated in vivo gene transfer in guinea pig middle ear mucosa.
AB  - This article describes a study designed to assess the feasibility of using
      recombinant adenovirus for delivering therapeutic peptides in vivo in the guinea
      pig middle ear cleft. A recombinant adenoviral vector AdCMVsp1 LacZ containing
      the Escherichia coli beta-galactosidase was injected into the middle ear space.
      Qualitative assessment of cell middle ear transfection was performed on day 2 by
      light microscopy study, after injecting a multiplicity of infection (MOI) ranging
      from 0 to 1000. At an MOI of 30, 30% of the promontory area epithelial cells were
      stained. An MOI of 50 stained 60% of the cells and an MOI of 100 or more stained
      more than 90% of the cells. The duration of cell transfection was studied after
      injecting an MOI of 50. The percentage of stained cells was 60% on day 2, 10% on
      day 7, and 0% on day 14. Middle ear mucosal inflammation, consisting of a
      granulocytic infiltrate, was observed when an MOI above 50 was used. Even at a
      high MOI (500), no staining could be found in the cochlea, in the facial nerve,
      in the brain, or in visceral organs. These data suggest that recombinant
      adenovirus vectors can be used to transfer genes in the middle ear. This method
      appears to be safe, and may be envisaged as a short-duration treatment to
      transfer genes in vivo in the treatment of middle ear diseases.

PMID- 9625262
TI  - Similarity of strain- and route-dependent murine responses to an adenovirus
      vector using the homologous thrombopoietin cDNA as the reporter genes.
AB  - Replication-deficient adenovirus (Ad) vectors are effective in transferring genes
      in vivo, but their use is associated with significant variation in the extent
      and/or duration of expression observed among different strains of experimental
      animals and different routes of administration of the vector. We have minimized
      the variables of the heterologous transgene and animal-to-animal variation by
      constructing an Ad vector encoding murine thrombopoietin (mTPO, AdmTPO), a
      homologous protein that induces a physiologic response (elevation of blood
      platelet levels) that can be followed sequentially over time in the same animal.
      Using the C57BL/6 and BALB/c stains, liver administration was accomplished by
      intravenous administration and skeletal muscle administration by direct
      injection. Despite the use of a homologous cDNA as a transgene, the Ad genome was
      rapidly lost from the liver after intravenous administration over the first 1 to
      2 weeks, with no difference in pattern of decline between the C57BL/6 and BALB/c
      strains. Both strains exhibited a cytotoxic T lymphocyte (CTL) response directed
      against the AdmTPO vector. Consistent with the decline in vector genome over
      time, the initial high levels of mTPO mRNA in the liver declined to an
      undetectable level within 2 weeks. Platelet counts peaked at 8- to 10-fold above
      baseline within the first 2 weeks, and then gradually declined, returning to
      normal level by 50 to 60 days. Intravenous administration of the AdmTPO vector to
      beta2-microglobulin-deficient mice resulted in a longer persistence of elevated
      platelets levels, although the eventual return of platelet levels to normal in
      these mice suggests the elimination of the Ad vector cannot be explained solely
      by CTL response. Although the intramuscular administration of the AdmTPO vector
      resulted in platelet levels with a lower peak and minor differences over time
      compared with the intravenous route, the C57BL/6 and BALB/c strains demonstrated
      the same rapid loss of Ad genome and mTPO mRNA levels in the muscle as in the
      liver. Together, these observations suggest that simplifying the experimental
      design by eliminating the variable of host response to a heterologous transgene,
      and by following the consequences of gene transfer in the same animals over time,
      there can be remarkable similarity in strain- and route-dependent responses to an
      Ad vector.

PMID- 9625263
TI  - Internal ribosomal entry site-containing retroviral vectors with green
      fluorescent protein and drug resistance markers.
AB  - To facilitate gene delivery into animal cells we developed and characterized a
      family of single-transcript vectors (STVs) with different selection markers
      expressed from the internal ribosomal entry site (IRES) of encephalomyocarditis
      virus (EMCV). Retroviral IRES-STVs (R-IRES-STVs) were assembled using an LNCX
      backbone (Miller and Rosman, 1989). In all of these constructs, a multiple
      cloning site (MCS) is located immediately downstream of the single promoter and
      is followed by the IRES sequence and a selectable marker. This configuration
      ensures that the MCS-inserted gene will be expressed in selected cells. The
      selectable markers of these vectors provide resistance to G418, puromycin,
      hygromycin B, histidinol D, and phleomycin. One STV contains green fluorescent
      protein (GFP) as a selectable marker, permitting FACS-mediated selection, which
      may prove useful in gene therapy applications. More than 70% of recipient cells
      could be infected with R-IRES-STVs after one round of infection. Up to 99% of
      infected cells expressed the reporter gene (GFP) after selection with an
      appropriate drug. When ecotropic receptor was delivered via R-IRES-STV into human
      HT1080 cells, populations of drug-selected cells as well as a majority of
      individual clones were found to be highly susceptible to infection by ecotropic
      retroviruses.

PMID- 9625264
TI  - Administration of neomycin resistance gene marked EBV specific cytotoxic T
      lymphocytes to patients with relapsed EBV-positive Hodgkin disease.

PMID- 9625265
TI  - Omission of the deconjugation step in urine analysis and the unaltered outcome of
      CYP2D6 phenotyping with dextromethorphan.
AB  - The present study was aimed at determining whether the deconjugation step in
      chemical analysis could be omitted without altering the outcome of phenotyping
      CYP2D6 with dextromethorphan. This drug and its metabolite, dextrorphan, were
      assayed by high-performance liquid chromatography (HPLC) in urine. Urinary levels
      of dextromethorphan and dextrorphan with and without enzymatic (beta
      glucuronidase) treatment of urine and the metabolic ratios for dextromethorphan
      were determined in 45 subjects. Although the enzymatic treatment did not alter
      the urinary concentration of dextromethorphan in both phenotypes, it increased
      the urinary concentration of dextrorphan in both poor and extensive metabolizers
      by 3.7- and 12.8-fold, respectively. A urinary unconjugated
      dextromethorphan/unconjugated dextrorphan metabolic ratio of 2.00 and a total
      dextromethorphan/total dextrorphan metabolic ratio of 0.30, respectively,
      identified three poor metabolizers. Enzymatic treatment decreased the urinary
      antimode value. Moreover, the urinary metabolic ratio based on unconjugated
      dextrorphan and dextromethorphan correlated well with that based on assay of
      total dextrorphan and dextromethorphan (rs = 0.9458, P < 0.001). The results show
      that urinary analysis of dextrorphan and dextromethorphan omitting the enzymatic
      deconjugation step is a fast, reliable and sensitive method and could be used for
      studying CYP2D6 type genetic polymorphism in man.

PMID- 9625266
TI  - Influence of d-limonene on the transdermal penetration of felodipine.
AB  - Felodipine is a calcium antagonist, one of the dihydropyridines, with potential
      application in transdermal therapeutic systems (TTS). Earlier studies reported
      that the high lag time of this drug limited its potential development in a TTS.
      The present study analyzes the effect of d-limonene at concentrations of 0.5, 1,
      5 and 10% on the transdermal penetration of this drug. The study was performed
      using a diffusion technique in vitro, with the skin of the hairless rat. d
      Limonene significantly reduced the lag time (Tl) to 1.4 h at a concentration of
      1% (compared with 9.8 h in its absence). Higher concentrations did not produce a
      significant decrease in the value of this parameter. The presence of d-limonene
      in the formulae produces an increase in the permeability constant (Kp) and the
      flux (J). The relation between this increase and the percentage of d-limonene was
      non-linear. An asymptotic value was obtained at a concentration of 5%, with
      increases of 993% and 1570% for Kp and J, respectively.

PMID- 9625267
TI  - A pharmacokinetic evaluation of pravastatin in middle-aged and elderly
      volunteers.
AB  - The pharmacokinetics of pravastatin, a serum-cholesterol-lowering drug, were
      studied in 20 middle-aged (46-59 years old, n = 8) and elderly subjects (60-81
      years old, n = 12). Pravastatin serum levels were determined by HPLC and solid
      phase extraction. Cmax was 48.9 +/- 7.1 ng/ml (mean +/- SEM, n = 20), and the
      mean AUC0-4.5h was 104.4 ng x h/ml (n = 5) for a 20 mg daily oral dose. A great
      interindividual variability was found for Cmax, which varied from 6.2 ng/ml to
      117.8 ng/ml on the 20 mg dose. As could be expected, Cmax and AUC0-4.5h were dose
      related, but Tmax and t1/2 were not. In six cases, the elimination of the drug in
      serum could be described by a single phase but in four cases with two phases. No
      significant difference was found in Cmax between the middle-aged and the elderly
      or between males and females.

PMID- 9625268
TI  - Comparative pharmacokinetic/pharmacodynamic analysis of proton pump inhibitors
      omeprazole, lansoprazole and pantoprazole, in humans.
AB  - The relationship between plasma concentrations and inhibitory effects on gastric
      acid secretion by proton pump inhibitors (PPIs) omeprazole (OPZ), lansoprazole
      (LPZ) and pantoprazole (PPZ), was analyzed using a
      pharmacokinetic/pharmacodynamic (PK/PD) model in humans. The estimated values of
      apparent reaction rate constant of PPI and H+,K+-ATPase (K) were 1.34 +/- 0.17
      (microM(-1) x h(-1)), 0.339 +/- 0.002 and 0.134 +/- 0.006 for OPZ, LPZ and PPZ,
      respectively. The estimated values of apparent turn-over rate constant of H+,K+
      ATPase (k) were 0.0252 +/- 0.0019 (h(-1)), 0.0537 +/- 0.0006 and 0.0151 +/-
      0.0002 for OPZ, LPZ and PPZ, respectively. The apparent dissociation constants of
      the H+,K+-ATPase-PPI complex (k/K x fp) corrected with plasma free fraction (fp)
      were about 1 nM for OPZ and LPZ and 2.3 nM for PPZ. Therefore, the potency of the
      inhibitory effect of PPZ on acid secretion may be slightly weaker than that of
      OPZ or LPZ. The apparent half lives (ln2/k) of the inhibitory effect on acid
      secretion were 12.9 h for LPZ, < 27.5 h for OPZ, and < 45.9 h for PPZ, the
      recovery rate of the inhibitory effect of PPZ on acid secretion was slowest among
      these PPIs. In conclusion, the relationship between plasma concentrations and
      inhibitory effects of PPIs on gastric acid secretion could be analyzed by the
      PK/PD model.

PMID- 9625269
TI  - Pharmacokinetics and hypotensive effect of deacetyl N-monodesmethyl diltiazem
      (M2) in rabbits after a single intravenous administration.
AB  - Deacetyl N-monodesmethyl diltiazem (M2) is a major metabolite of the widely used
      calcium antagonist diltiazem (DTZ). In order to study the pharmacokinetic and
      haemodynamic effects of this metabolite, M2 was administered as a single 5 mg/kg
      dose intravenously (i.v.) to New Zealand white rabbits (n = 5) via a marginal ear
      vein. Blood samples, blood pressure (SBP and DBP), and heart rate (HR) recordings
      were obtained from each rabbit up to 8 h, and urine samples for 48 h post-dose.
      Plasma concentrations of M2 were determined by HPLC. The results showed that
      there were no identifiable basic metabolites which could be quantified and
      characterized in the plasma. The apparent terminal t1/2 and AUC were 2.8 +/- 0.7
      h and 2000 +/- 290 ng x h/ml, respectively. The Cl and Clr of M2 were 38 +/- 4.8
      ml/min/kg and 0.57 +/- 0.23 ml/min/kg, respectively. M2 significantly decreased
      blood pressure (SBP and DBP) for up to 2 h post-dose (P < 0.05), but had no
      significant effect on the heart rate (P > 0.05). The Emax and EC50 as estimated
      by the inhibitory sigmoidal Emax model were 15 +/- 7% and 450 +/- 46 ng/ml,
      respectively, for SBP; 15 +/- 20% and 430 +/- 120 ng/ml for DBP.

PMID- 9625270
TI  - An attempt to establish an in vitro-in vivo correlation: case of paracetamol
      immediate-release tablets.
AB  - The purpose of this study was to investigate the possibility of developing
      different levels of in vitro-in vivo correlation for immediate-release
      paracetamol tablets using in vitro dissolution data obtained under various
      experimental conditions. The influence of agitation intensity and pH value of the
      dissolution media was investigated. The level B approach, using statistical
      moment analysis led to poor correlation results. The results obtained by
      numerical deconvolution in order to study level A correlation indicated that good
      correlation should be sought with moderate levels of agitation (beyond 50 rpm in
      rotating basket apparatus). Results obtained by numerical convolution showed the
      highest level of correlation, level A, with one-to-one relationship between
      observed and predicted in vivo profiles.

PMID- 9625271
TI  - Investigation of the metabolism of 7-(4-chlorbenzyl)-7,8,13,13a
      tetrahydroberberine chloride in the rat.
AB  - The metabolism of 7-(4-chlorbenzyl)-7,8,13,13a-tetrahydroberberine chloride
      (CTHB), a compound with promising pharmacological effects against arrhythmia, was
      investigated in rat bile. A metabolite and unchanged CTHB were found in the bile.
      Characterization and structural elucidation of the metabolite was achieved by
      LC/MS and LC/NMR. The following metabolic pathway is proposed: CTHB is
      metabolized by demethylation at position 10 to produce a new entity.

PMID- 9625272
TI  - Pharmacokinetics of [14C]-labelled Losigamone and enantiomers after oral
      administration to healthy subjects.
AB  - Losigamone ((+/-)-(R*,S*)-5-(2-chlorophenylhydroxymethyl)-4-methoxy-2 (5H)
      furanone; AO-33) is a new potential antiepileptic drug undergoing clinical
      development. In a crossover study, 200 mg [14C]-labelled Losigamone, as well as
      100 mg of each of the unlabelled enantiomers, was administered to 5 healthy
      volunteers as an oral suspension. The objectives of the study were to determine
      the mode of elimination, the excretion balance, metabolic profile, the in vitro
      and in vivo binding to plasma proteins and the pharmacokinetics of both
      enantiomers in plasma. From the plasma concentration-time profiles of [14C]
      radioactivity and unchanged Losigamone it can be concluded that the absorption of
      Losigamone occurs very rapidly and the plasma concentration of the parent
      compound versus total radioactivity was consistently about 40%. An overall
      recovery of total radioactivity of about 97% with 85% in urine and 12% in faeces
      was found. Protein binding was 50%. Losigamone was extensively metabolized, with
      only traces of unchanged drug found in urine. The predominant metabolic pathways
      are hydroxylation and conjugation. After administration of the pure enantiomers,
      significant differences in pharmacokinetics were observed. The mean oral
      clearance of the (-)-enantiomer was 1863 ml/min and of the (+)-enantiomer was 171
      ml/min. There was no chiral inversion after administration of the enantiomers.

PMID- 9625273
TI  - Interaction between grapefruit juice and diazepam in humans.
AB  - Grapefruit juice has been reported to markedly improve the bioavailability of
      triazolam, midazolam, terfenadine, cyclosporine and several dihydropyridine
      calcium channel blockers including felodipine, nifedipine, nitrendipine and
      nisoldipine. Because these drugs are metabolized by the hepatic cytochrome P450
      isozyme (CYP) 3A4, the inhibitory effect of grapefruit juice is thought to
      results from inhibition of CYP3A4. In this study, our aim was to investigate the
      effects of grapefruit juice on plasma concentrations of diazepam. Eight healthy
      male and female subjects participated in this study. Oral (5 mg) diazepam was
      administered with either 250 ml water and grapefruit juice. Blood samples were
      collected for a 24 h period, and whole blood concentrations of diazepam were
      measured enzyme immunoassay. The mean AUC(0-24) of diazepam was increased 3.2
      fold (P < 0.001) and Cmax was increased 1.5-fold (P < 0.05) by the grapefruit
      juice. Grapefruit juice postponed the tmax of diazepam from 1.50 h to 2.06 h (P <
      0.01).

PMID- 9625274
TI  - Pharmacokinetics of a nootropic agent, BMY-21502, and its metabolites in beagle
      dogs.
AB  - A preliminary investigation into the pharmacokinetics of BMY-21502, a nootropic
      agent, and two of its metabolites, BMY-42191 and BMY-40440, was performed in 4
      beagle dogs. Following oral dosing of a solution of BMY-21502 (0.61 mmoles),
      plasma samples were obtained for 24 h and analyzed for the three analytes by a
      validated HPLC assay. BMY-21502 was rapidly absorbed (Tmax = 0.5 +/- 0.3 h),
      followed by a rapid decline of the plasma levels (T1/2 = 0.95 +/- 0.1 h). The
      hydroxy metabolite, BMY-42191, was rapidly formed and the peak concentrations in
      plasma were obtained by 2.88 +/- 0.2 h. On the contrary, there was a considerable
      delay in the peaking of the ketone metabolite, BMY-40440 (Tmax = 6 h). The T1/2
      values for BMY-40440 (5.58 +/- 0.5 h) were longer than those for BMY-42191 (4.28
      +/- 1.2 h). Comparison of AUC values for BMY-42191 (326.43 +/- 63.3 h x microM)
      with those of BMY-40440 (67.52 +/- 8.4 h x microM) or BMY-21502 (69.35 +/- 7.3 h
      x microM) indicated that BMY-42191 was the major circulating species in dog
      plasma. In conclusion, the preliminary data indicate that the metabolism of BMY
      21502 is complex and may encompass hydroxy-ketone metabolic interconversions, as
      reported for other xenobiotics.

PMID- 9625275
TI  - Ritodrine sulphation in the human liver and duodenal mucosa: interindividual
      variability.
AB  - The beta2-adrenoceptor agonist ritodrine has a bioavailability of 30% due to its
      presystemic metabolism and sulphation is an important metabolic route. The
      interindividual variability in the rate of ritodrine sulphation in 100 specimens
      of human liver and duodenum is reported. The final concentrations of ritodrine
      were 2 mM (duodenum) and 20 mM (liver). The mean estimates of ritodrine
      sulphation rate were 490 pmol x min(-1) x mg(-1) (duodenum) and 140 pmol x min(
      1) x mg(-1) (liver). There was a 4-5-fold variation within +/- 2 SD units in the
      hepatic and duodenal rates of ritodrine sulphation. Statistical analysis revealed
      the presence of at least two subgroups of ritodrine sulphation. In the liver, 30%
      and 70% of the population fell into two subgroups with the mean estimates of
      ritodrine sulphation rate of 114 and 149 pmol x min(-1) x mg(-1), respectively (P
      < 0.05). In the duodenum, 25% and 75% of the population fell into two subgroups
      and the mean estimates of ritodrine sulphation rate were 332 and 538 pmol x min(
      1) x mg(-1), respectively (P < 0.05). The rates of ritodrine and 4-nitrophenol
      sulphation correlated highly in the liver (r = 0.865; P < 0.001) and the rates of
      ritodrine and dopamine sulphation correlated highly (r = 0.914; P < 0.001) in the
      duodenum. In both tissues, the rates of ritodrine and (-)-salbutamol sulphation
      underwent a similar extent of variation and correlated highly. The intrinsic
      clearance of ritodrine sulphation was over one order of magnitude higher in the
      duodenum than in the liver suggesting that the duodenum is an important site of
      ritodrine sulphation.

PMID- 9625276
TI  - Diet in phenylketonuria: how long? Policies under discussion.

PMID- 9625277
TI  - Energy intake and growth of 3- to 36-month-old German infants and children.
AB  - Recently, new estimations of the energy requirements of infants and children were
      proposed as a basis of new FAO/ WHO energy requirements. We have compared the
      energy intake of 354 healthy, well-nourished infants taking part in the Dortmund
      Nutritional and Anthropometric Longitudinal Designed Study (3-day-weighted diet
      records) with these new estimated energy requirements. The energy intake of
      breast-fed and formula-fed infants and the energy intake of the 1- to 3-year-old
      children in the study population corresponded well with the new estimated energy
      requirements, although these were considerably lower than the 1985 FAO/WHO energy
      requirements. Breast-feeding rates were lower and the introduction of beikost was
      earlier than the current recommendations. Height and weight, which were taken as
      global indicators of the adequacy of the energy intake, were in good accordance
      with The Netherlands' third nationwide survey. Our data indicate that the new
      estimations of energy requirement seem to be more appropriate than the 1985
      FAO/WHO energy requirements.

PMID- 9625278
TI  - Dietary fat level and short-term effects of a high-fat meal on food intake and
      metabolism.
AB  - After determining the dietary fat intake in 40 subjects based on a 7-day
      recording period, the effects of a high-fat breakfast (52% of metabolizable
      energy from fat) on postprandial fat and carbohydrate metabolism as well as on
      subsequent lunch intake were investigated in 28 lean, male subjects with habitual
      dietary fat intakes between 21 and 44% (of daily energy intake). Correlational
      analysis and comparisons between a low-fat group (LF; fat intake < or =35%, n =
      10) and a high-fat group (HF; fat intake > or =40%, n = 11) with a similar body
      mass index (LF: 22.7, HF: 22.4) and a low body fat content (LF and HF: 10.7)
      demonstrated that the fat level of the habitual diet did not affect the baseline
      values and the postprandial changes in the respiratory quotient and in the plasma
      levels of glucose, insulin, lactate, free fatty acids, beta-hydroxybutyrate, and
      triglycerides induced by the high-fat breakfast. Only the area under the curve
      for insulin was higher, and the lactate/insulin ratio was lower in the HF group
      than in the LF group. Moreover, hunger and satiety ratings and lunch intake
      (amount, duration, microstructure of eating) after the high-fat breakfast were
      similar in all subjects. Thus, the habitual level of dietary fat did not alter
      the acute effects of a fat-rich breakfast on whole-body and hepatic fatty acid
      oxidation and eating behavior at lunch under the present test conditions. Yet, a
      long-term high fat intake appears to have subtle effects on postprandial
      metabolism which are consistent with early signs of a developing insulin
      resistance.

PMID- 9625279
TI  - Effect of the source of dietary fat on postweaning lipogenesis in lean and fat
      pigs.
AB  - Twenty-four male piglets weaned after 21 days, 12 of the Large White lean breed
      (LW) and 12 of the Alentejano fat breed (AL), have been used to compare the
      effects of genotype and source of dietary fat on the activities of enzymes
      involved in lipogenesis and on the composition of selected fatty tissues. During
      4 weeks the piglets were fed isoenergetic and isonitrogenous experimental diets,
      containing 5 % of either olive oil or tallow. In AL piglets the acetylcoenzyme A
      carboxylase activity was three- and ninefold higher, the malic enzyme activity
      six- and fivefold, and the glucose-6-phosphate dehydrogenase activity was four-
      and fivefold higher in the dorsal subcutaneous and in the perirenal fat,
      respectively, than in LW piglets. In general, fatty tissues of the AL piglets
      contained a higher proportion of saturated fatty acids. Olive oil induced a
      significant increase in the activities of malic enzyme and glucose-6-phosphate
      dehydrogenase in both tissues, but only slightly increased the acetylcoenzyme A
      carboxylase activity in perirenal fatty tissues (p < 0.05). The fatty acid
      profile of the subcutaneous and of the perirenal fat was strongly affected by the
      composition of dietary fat. These observations showed that the source of dietary
      fat influenced markedly lipid metabolism and body composition since a very early
      age.

PMID- 9625280
TI  - Iron-manganese interactions in the evolution of iron deficiency.
AB  - This article examines the evolution of nutritional iron deficiency and the
      possible interactions with other minerals, such as manganese, in control and iron
      deficient rats. The evolution of iron deficiency was studied at 0, 10, 20, 30 and
      40 days of providing the animals with an iron-free diet (diet 0). It was found
      that the critical period in the development of nutritional iron deficiency occurs
      after 30-40 days without iron, at which moment the organism is unable to maintain
      hemoglobin levels without endangering the iron-dependent enzymatic groups which,
      in turn, are essential for life. It was also demonstrated that in a situation of
      iron deficiency, there occurs a greater absorption of manganese. It should be
      noted that this greater absorption of manganese is not reflected in the
      concentration of the mineral in the organs. Therefore, it is evident that the
      interactions of iron with manganese take place at the digestive level with no
      apparent consequences being observed at the metabolic level.

PMID- 9625281
TI  - Effects of low phosphate intake on bone and mineral metabolism in rats:
      evaluation by biochemical markers and pyridinium cross-link formation in bone.
AB  - We have investigated the changes in biochemical markers and in pyridinium cross
      links in bone in hypophosphatemic rats. Six-week-old female Wistar rats were
      divided into two groups (normal diet and a phosphate-deficient diet) and fed for
      8 weeks. A low phosphate intake caused a significant difference in the
      concentrations of osteocalcin and alkaline phosphatase with advancing rachitis as
      well as an increase in bone resorption marker concentrations in urine. Femur
      biochemical analysis revealed a significant (p < 0.005) increase in
      deoxypyridinoline per mole collagen in the phosphate-deficient group which
      suggested that urinary excretions of pyridinium cross-links might reflect not
      only bone resorption but also increased pyridinium cross-links in bone matrix
      collagen. Our results demonstrate that a low phosphate intake causes an increase
      of pyridinium cross-link formation as well as a discrepancy between the
      circulation levels of alkaline phosphatase and osteocalcin with advancing
      rachitis. These alterations induced by low phosphate intake should be considered
      when interpreting the values of biochemical markers.

PMID- 9625282
TI  - Weak relationship between symptom perception and objective hypoglycaemia-induced
      changes of autonomic function in hypoglycaemia unawareness in diabetes.
AB  - To assess the relationship between symptom perception and neurophysiological
      characteristics in hypoglycaemia unawareness, we investigated the awareness of
      symptoms, objective changes of autonomic function and counter-regulatory
      neuroendocrine responses to hypoglycaemia in intensively treated type I (insulin
      dependent) diabetic patients with different degrees of hypoglycaemia unawareness.
      Hypoglycaemia (venous plasma glucose below 2.2 mmol/l) was induced with an
      intravenous insulin bolus in subjects with a history of repeated severe
      hypoglycaemia and hypoglycaemia unawareness (n = 10) and in a comparable group
      with good awareness of hypoglycaemia (n = 8). Autonomic symptoms, selected
      parameters of autonomic function and counter-regulatory hormones were assessed
      serially. Although hypoglycaemia was more pronounced in unaware patients (1.6 vs
      2.0 mmol/l, P = 0.05), their induced adrenaline response was markedly impaired
      (delta adrenaline: 1.25+/-1.10 vs 2.55+/-1.46 nmol/l, P = 0.05). Astonishingly,
      differences between both patient groups in the course of autonomic function
      changes did not reach the level of significance (P = 0.35-0.92), although the
      unaware group reported markedly fewer autonomic symptoms, both neurogenic (P =
      0.001) and neuroglycopenic (P = 0.04) than the aware group. This study indicates
      that in hypoglycaemia unawareness even extensive changes in autonomic function
      are not sufficient for the perception of hypoglycaemia and confirms that the
      central nervous system plays an important role in the awareness of hypoglycaemia.

PMID- 9625283
TI  - Neuropeptide contents in the duodenum of non-obese diabetic mice.
AB  - Twelve pre-diabetic and 12 diabetic female NOD mice aged 22-24 weeks were
      studied. As controls, 12 female BALB/cJ of the same age and sex were used. The
      duodenal content of several neuropeptides, namely vasoactive intestinal
      polypeptide (VIP), neurotensin, neuropeptide Y (NPY), galanin, gastrin-releasing
      peptide (GRP) and enkephalin was determined by radioimmunoassay of tissue
      extracts. The VIP content in duodenal extracts from both pre-diabetic and
      diabetic NOD mice was significantly higher than that of the controls. The
      enkephalin content of the duodenum of diabetic mice was significantly higher than
      that of the controls, while no significant difference was found between the
      controls and pre-diabetic mice. There was no statistically significant difference
      between controls and NOD mice regarding the duodenal content of neurotensin, NPY,
      galanin or GRP. It has been suggested that the high duodenal content of VIP
      appears to be primary to the onset of diabetes and that the high enkephalin
      content may be attributable to the diabetic state. The changes in the duodenal
      content of VIP and enkephalin reported here in an animal model for diabetes type
      I might be of relevance for the gastrointestinal complications occurring in human
      diabetes.

PMID- 9625284
TI  - Lipoprotein(a) levels and apolipoprotein(a) polymorphism in type 1 diabetes
      mellitus: relationships to microvascular and neurological complications.
AB  - To investigate plasma concentrations of lipoprotein(a) [Lp(a)] and
      apolipoprotein(a) [apo(a)] polymorphism in relation to the presence of
      microvascular and neurological complications in type 1 diabetes mellitus, 118
      young diabetic patients and 127 age-matched controls were recruited. Lp(a) levels
      were higher in patients than in controls, but the apo(a) isoforms distribution
      did not differ between the two groups [higher prevalence of isoforms of high
      relative molecular mass (RMM) in both groups]. Microalbuminuric patients had
      Lp(a) levels significantly greater than normoalbuminuric patients, and
      normoalbuminuric patients showed higher Lp(a) levels than controls. Patients with
      retinopathy or neuropathy showed similar Lp(a) levels to those without
      retinopathy or neuropathy. No differences in apo(a) isoforms frequencies were
      observed between subgroups with and without complications (higher prevalence of
      isoforms of high RMM in every subgroup). However, among patients with
      retinopathy, those with proliferative retinopathy had higher Lp(a) levels and a
      different apo(a) isoforms distribution (higher prevalence of isoforms of low RMM)
      than those with non-proliferative and background retinopathy (higher prevalence
      of isoforms of high RMM). Our data suggest that young type 1 diabetic patients
      without microalbuminuria have Lp(a) levels higher than healthy subjects of the
      same age. Lp(a) levels are further increased in microalbuminuric patients. High
      Lp(a) levels and apo(a) isoforms of low RMM seem to be associated with the
      presence of proliferative retinopathy, but have no relation to neuropathy.

PMID- 9625285
TI  - Vagal efferent control of electrical properties of the heart in experimental
      diabetes.
AB  - Autonomic neuropathy is a common and severe complication of diabetes mellitus
      that leads to dysfunction of the cardiovascular system. The reduced ability to
      finely regulate heart rate is attributed to an impairment of cardiac
      parasympathetic regulation, but it is not known whether this is due to
      parasympathetic neuropathy and/or direct cardiac impairments. Therefore, we
      recorded the electrocardiogram of streptozotocin-induced diabetic rats under
      basal conditions and during electrical stimulation of the vagus nerve. We used
      the neurotrophic agent Org 2766, an adrenocorticotropic hormone [ACTH]-(4-9)
      analogue, to investigate the involvement of a neurogenic component in the altered
      vagal control of heart rate. The R-R interval was increased and atrioventricular
      transmission time unchanged 1 week after diabetes induction and remained so until
      20 weeks. Treatment with Org 2766 could not prevent the bradycardia. After
      bilateral vagotomy, both diabetic and non-diabetic rats had the same R-R and P-R
      interval. The response of the R-R interval to electrical stimulation of the right
      vagus nerve was impaired, and this impairment was not reversed by Org 2766 in
      diabetic rats. These results suggest that neurogenic factors are of little or no
      importance in the impaired parasympathetic control of heart rate seen in
      experimental diabetes.

PMID- 9625286
TI  - Effects of a 7-day infusion of glucose on insulin secretion in vivo and in vitro
      in ventromedial hypothalamic-lesioned obese rats.
AB  - Excessive stimulation of insulin secretion may be one cause of the beta-cell
      dysfunction induced by hyperglycemia. We investigated a possible link between the
      prior endogenous hypersecretion of insulin and this dysfunction by performing a 7
      day glucose infusion (50% wt/vol, 1.2 ml/h) on ventromedial hypothalamic VMH
      lesioned hyperinsulinemic rats. Intravenous glucose tolerance tests (i.v.GTT 1.0
      g/kg) revealed that a 3-day glucose infusion enhanced the insulin responses in
      both the sham- and VMH-lesioned rats compared with saline infusions. A similar 7
      day glucose infusion enhanced the insulin response to glucose in sham-lesioned
      rats but not in VMH-lesioned rats. Batch-incubation of islets isolated from sham
      lesioned rats showed an enhanced insulin response to glucose after 7 days of
      glucose treatment compared with the saline infusions. Conversely, the glucose
      infusion in VMH-lesioned rats markedly suppressed the in vitro insulin response.
      In sham- and VMH-lesioned rats, similar islet insulin contents were produced by
      saline and glucose treatments. Electron microscopy revealed that glucose
      infusions impaired the granule-releasing function of the beta-cells in VMH
      lesioned rats, while insulin synthesis was accelerated in either group. These
      findings support the notion that excessive secretion is partly responsible for
      the beta-cell dysfunction induced by hyperglycemia without signs of exhaustion.

PMID- 9625287
TI  - European study on dose-response relationship of acarbose as a first-line drug in
      non-insulin-dependent diabetes mellitus: efficacy and safety of low and high
      doses.
AB  - The aim of this double-blind, placebo-controlled, multinational, five-arm study
      was to investigate the dose-response relationship of acarbose as a first-line
      drug in the treatment of type 2 diabetes (non-insulin dependent) over a range of
      minimal and maximal doses according to the European recommendations. The study
      included 495 patients from 7 countries who were insufficiently controlled with
      diet alone (glycosylated haemoglobin HbA1C 6.5%-9%). Acarbose, 25, 50, 100 or 200
      mg t.i.d., or placebo t.i.d. was given for 24 weeks. Even a low dosage of 25 mg
      t.i.d. acarbose reduced fasting and postprandial blood glucose levels (1 h
      postprandial -11.6%; 2 h postprandial -11.3%). Acarbose in a dosage of 200 mg
      t.i.d. had the greatest effect on these parameters. In the placebo group the mean
      2 h postprandial area under the curve (AUC) value for blood glucose was 22.6
      mmol/l after 24 weeks' therapy. The mean 2 h postprandial AUC values in the
      patients given acarbose at doses of 25, 50, 100 and 200 mg t.i.d. were found to
      be 21.2, 19.6, 20.3 and 18.5 mmol/l, respectively. The corresponding HbA1C values
      for the placebo and acarbose groups were 7.83%, 7.37%, 7.08%, 6.98% and 6.79%.
      Interestingly, there was a plateau of blood glucose level at a dosage of 50-100
      mg t.i.d. The frequency of flatulence decreased with the duration of drug
      therapy, but we could not find a linear relationship between doses of acarbose
      and the gastrointestinal side effects. Less than 3% of patients stopped tablet
      intake due to adverse events.

PMID- 9625288
TI  - With regard to glycohemoglobin measurement: are we sure that high-performance
      liquid chromatography currently works in the clinical routine?
AB  - The clinical usefulness of glycated hemoglobin (HbA1C) depends crucially on the
      accuracy and precision of its assay. When we compared an immunological bench-top
      analyzer (DCA 2000, Bayer Diagnostici, Milan) to the high-performance liquid
      chromatography (HPLC) reference method used in a routine hospital laboratory
      (Diamat and Fast Diamat, Bio-Rad Lab., Milan) by assaying multiple control sera,
      we found so many sources of systematic analytical errors in the routine use of
      HPLC as to compromise between-assay precision. DCA 2000 showed intra- and
      interassay coefficients of variation (CV) of 1.1% and 2.3% with the normal
      standard serum, 1.0% and 4.2% with the pathological one; Diamat yielded CVs of
      1.3% and 7.0%, 1.3% and 5.7%, respectively. Although the measurement of 161 blood
      samples showed that Diamat usually overestimated HbA1C (paired t-test, P<0.001),
      a great variability of Diamat performance became evident when the relationship
      Diamat vs DCA was evaluated day by day over 17 days of observation (analysis of
      variance, ANOVA, P<0.001). Intra- and interassay CVs of Fast Diamat initially
      (new instrument still on approval) were 0.6% and 2.5% (normal standard serum),
      0.3% and 1.9% (high standard serum), yet after 6 months of routine laboratory
      use, they became 3.1% and 3.2%, 1% and 12.3%, respectively. Main sources of error
      were: inaccurate autodilution, unsuitable parameter settings, disregard of the
      maintenance schedule. We conclude that the tendency to overlook major critical
      aspects in the routine use of HPLC is detrimental to the quality of HbA1C
      determination and implies the loss of HbA1C value in clinical practice. Both
      carefully supervising laboratory quality and checking the likelihood of the
      analytical result with the clinical setting appear even more important.

PMID- 9625289
TI  - Comparison of serum fructosamine vs glycohemoglobin as measures of glycemic
      control in a large diabetic population.
AB  - In diabetic patients, measurement of glycohemoglobin (HbA1C) is widely accepted
      as the standard method for determining long-term glycemic control. Another test,
      the serum fructosamine test, has been suggested as a less costly alternative. To
      compare these two tests, we evaluated how well each correlated with fasting blood
      glucose and how well each could predict the degree of glycemic control perceived
      by treating physicians. Among 222 diabetic subjects, fructosamine (r=0.74) and
      fructosamine corrected for serum albumin (c-fructosamine) (r=0.79) correlated
      better with fasting blood glucose than did HbA1C (r=0.68) (P<0.05). Among 450
      diabetic subjects, fructosamine, c-fructosamine, and HbA1C showed similar error
      rates (23%-26%) when discriminating between subjects who had either poor vs not
      poor control or poor-to-fair versus good-to-excellent control. However, receiver
      operating characteristic curves for these tests indicated that HbA1C was the best
      discriminator because it showed a 9% to 10% greater area under the curve
      (P<0.05).

PMID- 9625290
TI  - Markers of insulin resistance are associated with cardiovascular morbidity and
      predict overall mortality in long-standing non-insulin-dependent diabetes
      mellitus.
AB  - The aim of this study was to evaluate the influence of endogenous insulin levels
      and of insulin administration on coronary heart disease (CHD) and on mortality in
      a cohort of patients with long-standing non-insulin-dependent diabetes mellitus
      (type 2). In a cross-sectional study, 93 patients (known duration 17 +/- 8 years,
      mean+/-SD) with poor metabolic control (glycosylated hemoglobin, HbA1C 9.3%+/
      2.09%) were evaluated for CHD, for insulin release (C-peptide), for clinical and
      metabolic parameters including body mass index (BMI), smoking habits, arterial
      blood pressure (BP), blood lipids, kidney function, and proteinuria. Life status
      was ascertained 5 years later by direct examination or through death
      certificates. At entry, 54 out of 93 patients had CHD; after 5 years, 25 patients
      had died. Comparisons performed on patients of the same age range showed that
      patients with CHD (34 vs 24) had a greater BMI, higher diastolic BP, higher
      creatinine, triglyceride and uric acid levels, and higher fasting and i.v.
      glucagon-stimulated C-peptide release. By logistic stepwise regression analysis,
      fasting C-peptide and triglycerides were independently associated with CHD. In
      the follow-up study, surviving patients (39 vs 19) showed at baseline lower
      triglyceride and creatinine levels, were less frequently affected by CHD, and
      received lower doses of insulin; by logistic stepwise regression analysis,
      presence of CHD, dose of insulin, and creatinine levels were independent risk
      factors for mortality. These data indicate that in patients with long-standing
      type 2 diabetes mellitus and poor metabolic control, CHD and overall mortality
      are related to insulin release and to insulin administration, suggesting that
      markers of insulin resistance represent additional risk factors for CHD and for
      mortality. Reduction of insulin resistance, together with achievement of good
      metabolic control, might prevent morbidity and mortality in long-standing type 2
      diabetes mellitus.

PMID- 9625291
TI  - Family history and risk of insulin-dependent diabetes mellitus: a population
      based case-control study.
AB  - Insulin-dependent diabetes mellitus (type 1) is a common chronic disease of
      childhood occurring throughout the world. In the literature, its most important
      determinants include genetic, environmental and familial factors. We evaluated
      family history as a determinant of the risk of type 1 diabetes mellitus with a
      population-based case-control study. Information about type 1 patients was taken
      from the dedicated register of the Abruzzo Region; the register has been
      collecting incident cases in the age group 0-14 years, diagnosed between 1
      January 1990 and 31 December 1996. The control group was taken from the lists of
      patients attending family pediatricians. The family history data for type 1 and
      type 2 patients was obtained by a questionnaire, administered to their parents.
      The risk of type 1 diabetes mellitus associated with its occurrence in first- and
      second-degree relatives was estimated using logistic regression methods. Our
      results show that the risk is indeed increased with a positive family history
      (OR=3.96; 95% CI 1.54-10.14). This shows that the risk of type 1 diabetes
      mellitus for children whose fathers are affected by the disease is 11 times
      higher with respect to controls. Moreover, the risk for children whose brothers
      are affected by the disease is 20 times higher with respect to controls. In
      contrast, a family history for type 2 diabetes mellitus does not influence the
      risk.

PMID- 9625292
TI  - Nicotinamide improves insulin secretion and metabolic control in lean type 2
      diabetic patients with secondary failure to sulphonylureas.
AB  - Eighteen patients with non-insulin-dependent (type 2) diabetes mellitus of normal
      body weight [body mass index (BMI) <25 kg/m2] without signs of autoimmunity
      [negative for islet cell antibodies (ICA)], with secondary failure of
      sulphonylureas, defined as persistent hyperglycaemia in spite of maximal doses of
      sulphonylureas, were evaluated for C-peptide release under basal conditions and 6
      min after i.v. glucagon, for glycosylated haemoglobin (HbA1C), and for fasting
      and mean daily blood glucose levels. They entered a 6-month, single-blind study
      in which they were randomly assigned to one of three treatments: (1) insulin plus
      nicotinamide (group 1, 0.5 g, three tablets/day); (2) insulin plus placebo (group
      2, 3 tablets/day); (3) current sulphonylureas plus nicotinamide (group 3, 0.5 g,
      three tablets/day). They were re-evaluated for C-peptide, HbA1C, and fasting and
      mean daily blood glucose levels after 6 months. Compared with group 2, C-peptide
      release increased in both groups 1 and 3, while HbA1C, fasting and mean daily
      blood glucose levels improved in the three groups to the same extent. With
      multiple regression analysis, nicotinamide administration was the only
      significant factor for the improvement of C-peptide release. These data indicate
      that nicotinamide improves C-peptide release in type 2 diabetic patients with
      secondary failure of sulphonylureas, leading to a metabolic control similar to
      patients treated with insulin.

PMID- 9625293
TI  - Serum 1,5-anhydro-D-glucitol levels in liver cirrhosis.
AB  - We studied the serum 1,5-anhydro-D-glucitol (AG) levels, a marker of glycemic
      control, in liver cirrhotic patients who had no evidence of glycosuria in 24-h
      urine samples in order to clarify the effects of impaired liver function on serum
      AG metabolism. We showed first that serum AG concentrations were significantly
      lower in cirrhotic patients than in age- and sex-matched healthy controls (17.6+/
      1.6 vs 26.3+/-1.7 microg/ml, P<0.05). Moreover, serum AG levels were found to be
      positively correlated with both serum cholinesterase and albumin levels. The
      observations indicate that serum AG levels were decreased in liver cirrhosis,
      especially in cases of severely reduced hepatic functions, suggesting the
      possibility of altered AG synthesis in liver cirrhosis.

PMID- 9625294
TI  - Scientific conference on the genome: applications to cardiovascular biology.

PMID- 9625295
TI  - Progressive disease or protective immunity to Leishmania major infection: the
      result of a network of stimulatory and inhibitory interactions.
AB  - The study of experimental infection of inbred strains of mice with the
      intracellular protozoan parasite Leishmania major has contributed significantly
      not only to our understanding of this fascinating host/parasite relationship but
      also to that of many basic immunological phenomena. Much has been learned about
      the cognate interaction of antigen-specific T cells and antigen-presenting cells,
      about cytokine and T cell subset regulation, and the requirements for
      costimulation. Specifically, the immune response to experimental L. major
      infection is the paradigm for polarized T helper cell (Th) 1 and Th2
      differentiation. In this model system a Th1 response characterized by interleukin
      (IL)-2 and interferon (IFN)-gamma secretion leads to self-curing disease, whereas
      a Th2 response (IL-4, IL-10) leads to nonhealing disease. Numerous manipulations,
      including the injection of cytokines and of neutralizing anti-cytokine
      antibodies, cytokine transgene expression, and more recently cytokine and
      cytokine receptor gene knockout studies, have all provided intriguing new pieces
      to the still incomplete mosaic of our understanding of the immune response. Some
      of these findings were clearly unexpected and are still incompletely understood.
      For instance, based on earlier neutralizing anti-IL-4 monoclonal antibody
      injection studies, IL-4 gene-disrupted BALB/c mice were expected to be unable to
      mount the biased Th2 response typical of the IL-4+/+ wild-type mice and to be
      able to control their lesions; quite unexpectedly, the BALB/c IL-4 knockout mice
      remain unable to heal their L. major infection. Based on these unexpected
      findings, we reexamine the literature in an attempt to resolve this apparent
      paradox and to relate the large body of experimental findings in the mouse system
      to that which is known about natural and experimental infections in the human.

PMID- 9625296
TI  - Oxygen, genes, and development: an analysis of the role of hypoxic gene
      regulation during murine vascular development.
AB  - Development of the mammalian cardiovascular system is a complex process guided by
      both genetic and environmental components. Significant advances in the genetics
      of vascular development have been accomplished most recently by the analysis of
      multiple "knockout" and transgenic mice which exhibit varying degrees of impaired
      vascularity. This review focuses on the potential of the environment of the
      developing embryo to affect its development. In particular we analyze the
      evidence implicating the ability of physiological parameters such as oxygen and
      glucose concentrations within and surrounding the embryo to affect the expression
      of genes critical for vascular development. We conclude that the vascularization
      of a developing mammalian embryo is a plastic process dependent on the dynamic
      interaction between fundamental genetic and physiological factors.

PMID- 9625297
TI  - Galectins: versatile modulators of cell adhesion, cell proliferation, and cell
      death.
AB  - Lectins, or carbohydrate binding proteins, recognize specific oligosaccharide
      structures on glycoproteins and glycolipids. Several families of animal lectins
      have been identified; for some of these lectins, functions such as leukocyte
      adhesion and microbial opsonization have been described. The galectins are a
      family of lectins found in species ranging from sponges and nematodes to humans.
      Members of the galectin family have been proposed to mediate cell adhesion, to
      regulate cell growth, and to trigger or inhibit apoptosis. The expression pattern
      of different galectins changes during development, and this pattern is also
      altered at sites of inflammation and in breast, colon, prostate, and thyroid
      carcinomas. In addition, the level of expression of some galectins by tumor cells
      has been shown to be correlated with metastatic potential. The mechanisms by
      which galectins exert these diverse effects remain largely unknown. Some
      glycoprotein counterreceptors recognized by certain galectins have been
      identified; this is an important first step in understanding the cell-type
      specific effects of different galectins. This review discusses the way in which
      the modulation of galectin activity may affect strategies for treatment of a
      variety of human diseases, including autoimmunity and cancer.

PMID- 9625298
TI  - Cell biology, clinicopathological profile, and classification of gastro
      enteropancreatic endocrine tumors.
AB  - Recent developments in the field of endocrine cell biology and pathology at both
      morphological and molecular levels are briefly outlined and discussed as a basis
      for endocrine tumor characterization. The main tools available for identifying
      the endocrine nature of the tumors, their pathogenetic interpretation. and
      experimental reproduction with special emphasis on tumor antecedents are
      reported. Based on this, classifications of endocrine tumors of the pancreas and
      gastrointestinal tract are developed, covering most clinical (hyperfunctional
      syndromes included), pathological, and biological patterns, with special emphasis
      on tumor prognosis.

PMID- 9625299
TI  - Hedgehog's escape from Pandora's box.
AB  - The Hedgehog family of secreted glycoproteins proteins plays multifarious roles
      during vertebrate embryogenesis. In both the Drosophila and vertebrate embryo
      correct deployment of Hedgehog-like proteins is critical for the generation of
      pattern in many tissues and organs. New evidence now reveals that genes involved
      in hedgehog signalling are mutated in a number of common human genetic disorders,
      including skin cancer and craniofacial defects. The understanding of how cells
      generate, receive and transduce the Hedgehog signal during development has led to
      the establishment of molecular paradigms for the pathogenesis of these diseases.
      These studies clearly illustrate that knowledge of the normal role of a gene
      during development is critical for generating an understanding of the disease
      state in which it is mutated.

PMID- 9625300
TI  - Unchanged protein expression of sarcoplasmic reticulum Ca2+-ATPase,
      phospholamban, and calsequestrin in terminally failing human myocardium.
AB  - The enhanced diastolic Ca2+ levels observed in cardiac myocytes from patients
      with idiopathic dilated cardiomyopathy (DCM) may be either a consequence of
      functional impairment of sarcoplasmic reticulum calcium-ATPase (SERCA 2) and its
      regulator protein phospholamban or due to a reduction in the number of SERCA 2
      proteins. As different myocardial membrane preparations may lead to different
      accumulation of proteins, the present study evaluated two different membrane
      preparations, in human failing and nonfailing myocardium for comparison of SERCA
      2 activity and the protein expression of SERCA 2 and phospholamban. Crude
      membranes and tissue homo-genates without any centrifugation steps were prepared
      from human nonfailing hearts (donor hearts, NF, n=18) and terminally failing
      hearts (heart transplant, DCM, n=18). Calsequestrin protein expression was used
      as an internal control for overall protein expression. In both crude membranes
      and homogenates maximal SERCA 2 activity (Vmax) was significantly reduced in
      failing heart preparations (NF crude membranes, 130+/-8; DCM crude membranes,
      102+/-5 nmol ATP/mg protein per minute). In contrast, the protein expression of
      SERCA 2 (NF crude membranes, 488+/-35; DCM crude membranes, 494+/-42; P=0.92),
      phospholamban (NF crude membranes, 497+/-51; DCM crude membranes, 496+/-45;
      P=0.98) and calsequestrin (NF crude membranes, 109+/-06; DCM crude membranes,
      107+/-08; P=0.84) was unchanged in NF and DCM hearts in both preparation methods.
      This was also the case when the protein expression was normalized to
      calsequestrin protein levels. Preparation of sarcoplasmic reticulum in crude
      membranes led to enhanced purification and consequently higher SERCA 2,
      phospholamban, and calsequestrin protein levels in crude membranes than in the
      homogenates, which was paralleled by an increase in SERCA 2 enzyme activity. In
      conclusion, the altered Ca2+ handling in DCM may be a consequence of reduced
      SERCA 2 enzyme activity and not the result of differences in protein expression
      of the Ca2+ regulating proteins SERCA 2, phospholamban, and calsequestrin in
      human myocardium. The present study emphasizes the importance of different
      myocardial membrane preparations with respect to quantitative investigations of
      protein expression and function.

PMID- 9625301
TI  - Interferons impair early transgene expression by adenovirus-mediated gene
      transfer in muscle cells.
AB  - Recombinant adenovirus (AVR) promises to be an efficient vector in gene therapy
      for neuromuscular diseases, but in preclinical experiments the expression of
      therapeutic genes is shorter lived in immunocompetent animals than in
      immunocompromised hosts. Interferons (IFN), which are known to have a role both
      in early antiviral activity and in late cytotoxic immunoreaction against the
      virus or transduced cells, may influence the efficiency of gene transfer. In this
      study we investigated the role of IFNs in determining the efficiency of gene
      transfer by AVR. AVRs expressing beta-galactosidase (beta-gal) from either a
      cytomegalovirus (CMV) or a troponin-I promoter were used. Muscle cells were
      infected by AVR after exposure to various IFNs. The alphaIFN treatment
      significantly reduced (up to fivefold) the CMV promoter-driven gene expression in
      muscle cells in vitro and in immature muscles in vivo, while the least effective
      inhibitor was betaIFN. The decrease in gene expression by IFNs was more
      pronounced with the CMV-driven transgene than troponin-I promoter-driven one and
      was due to a decrease in transcript level. Intrinsic IFNs that are triggered by
      AVR administration can decrease the efficiency of gene transfer in muscle cells.
      Therefore the use of muscle specific promoters in AVR and/or IFN inhibitory
      agents will likely improve the prospects of effective gene therapy by AVR.

PMID- 9625302
TI  - The level of erbB2 expression predicts sensitivity to the cytotoxic effects of an
      intracellular anti-erbB2 sFv.
AB  - We have previously demonstrated that an intracellular antibody (sFv) directed
      against erbB2 can achieve a specific cytotoxicity in erbB2 overexpressing cancer
      cells of varying histogenesis. In order to further delineate the mechanistic
      basis of the induced apoptosis, transient and stable cotransfections were
      performed. Transient cotransfection of erbB2 mutant and chimeric molecules
      demonstrated that the cytoplasmic domain of erbB2, or the homologous cytoplasmic
      domain of the epidermal growth factor receptor, is required for apoptosis
      induction. These results were confirmed in assays utilizing differential
      derivation of stable clones. To examine the effects of varying ratios of the anti
      erbB2 sFv and its target erbB2 we performed additional cotransfection experiments
      in erbB2 negative target cells. When erbB2 levels are held constant, observed
      cytotoxicity is proportional to the amount of sFv added. In addition, when sFv
      levels are held constant, increasing levels of cotransfected erbB2 can overcome
      the apoptotic response. These results indicate that a minimal threshold level of
      the sFv and its target are required to induce cytotoxicity. To examine this
      phenomenon in an erbB2 positive cell line, SKOV3 ovarian carcinoma cells were
      utilized to derive a stable clone expressing low levels of sFv. When this cell
      line was compared to the parental SKOV3 cell line, it was shown that less
      exogenous sFv was needed to induce cytotoxicity in the clone already expressing
      low levels of sFv, indicating that endogenous and exogenous levels of sFv are
      additive. In summary, the results presented here indicate that the carboxy
      terminus of the intracellular domain of the erbB2 molecule is involved in the
      induction of apoptosis. Furthermore, the expression levels of the sFv and its
      target protein need to overcome a threshold level in order to achieve a cytotoxic
      response.

PMID- 9625303
TI  - Immunohistochemical expression of tyrosine kinase (Trk) receptor proteins in
      mature neuronal cell tumors of the central nervous system.
AB  - The interactions of neurotrophins with the Trk family of tyrosine kinase
      receptors result in growth and maturational changes in neuronal cells. Although
      the histogenesis of brain tumors composed of mature neuronal cells is still not
      completely understood, neurotrophins and Trk receptors may be involved in the
      evolution, maturation, and persistence of these tumors. The clinical and anatomic
      pathological features of 8 primary neuronal cell tumors (ganglioglioma: 3 cases,
      cerebral neurocytoma: 3 cases, intraventricular neurocytoma: 2 cases) occurring
      in the central nervous system (CNS) have been examined. In addition to routine
      histological examinations, immunohistochemistry was used to evaluate the
      expression of neurotrophin receptors (TrkA, TrkB) and of neuronal differentiation
      markers such as neuron-specific enolase, neurofilament, synaptophysin, and
      chromogranin A. While neither TrkA nor TrkB expression was demonstrated in 2
      intraventricular neurocytomas, the remaining 6 tumors did show positive
      immunohistochemical staining for TrkA and/or TrkB proteins; for TrkA protein,
      ganglionic cells showed membraneous or cytoplasmic staining, while small non
      ganglionic neuronal cells with scant cytoplasm occasionally showed positive
      cytoplasmic immunoreactivity. For TrkB protein, small non-ganglionic neuronal
      cells showed a more intense immunoreaction than ganglionic cells. Gangliogliomas
      with high TrkA and TrkB expression showed higher levels of neuronal
      differentiation, as demonstrated by the neuron-specific enolase and neurofilament
      immunoreactivity. The existence of neurotrophin receptors in the tumor cells thus
      suggests that neurotrophic influence are involved in the evolution and subsequent
      cellular maturation in neuronal cell tumors of the CNS.

PMID- 9625304
TI  - Motor neuron disease and HIV-1 infection in a 30-year-old HIV-positive heroin
      abuser: a causal relationship?
AB  - Although human retroviruses seem plausible agents of motor neuron diseases, there
      are only few reports of patients infected by the human immunodeficiency virus,
      with documented motor neuron disorder. That retroviral infections may cause motor
      neuron pathology by various mechanisms in animals and humans is known.
      Neurological symptoms potentially attributed to damage of lower motor neurons are
      often described during the course of HIV-1 infection and AIDS, however, it is
      often difficult to establish whether the disorder is primarily affecting the
      perikarya of lower motor neurons, or whether it is due to a focal proximal
      axonopathy, or to a dying-back process. We report a 30-year-old heroin abuser,
      HIV-1 positive, who presented a rapidly progressive limb weakness, muscle
      wasting, and bulbar signs, in absence of sensory loss of cerebellar and pyramidal
      signs. Imaging studies were negative. CSF showed increased protein content,
      negative cytology, and no oligoclonal bands. Serum protein electrophoresis,
      urinary heavy metal, and viral researches were negative. CD4 cells were counted
      340 mm3 with a CD4-CD8 ratio equal to 0.4. Electrophysiology showed acute and
      chronic neurogenic changes, confirmed by muscle biopsy. Conduction studies along
      motor and sensory nerves fell within normal range. Biopsy of sural nerve revealed
      mild myelinated and unmyelinated fiber loss, occasional degeneration and
      regeneration, unremarkable inflammation. Despite treatment with AZT, zalcitabine,
      and steroids, the patient died after 3-month illness. Neuropathology showed
      normal cortical cell Betz's, and hemispheric white matter. Brain stem motor
      nuclei (inferior olival, dorsal motor of the vagus, hypoglossal) showed atrophy
      and intracytoplasmatic lipofuscin accumulation. Vacuolization, central
      chromatolysis, and neuronophagia were rarely seen. As associated pathology, in
      the fourth ventricle there were two small subependymal foci of demyelination,
      with reactive astrocytes and vascular proliferation. A possible crucial role of
      the HIV-1 infection in the development and progression of our patient's illness
      is considered in view of the known altered immunity proved in MND and ALS cases.

PMID- 9625305
TI  - The natural history of a recurrent central neurocytoma-like tumor.
AB  - The central neurocytoma was first recognized as a distinct entity in 1982. The
      original description was of a low grade, intraventricular neoplasm composed of
      uniform cells showing neuronal differentiation, and having a very favorable
      prognosis after surgery. Subsequently rare cases have been described showing
      malignant histological features but retaining the morphological characteristics
      that justify inclusion in this category. The behavior of such cases has yet to be
      determined. We report a case of a longstanding intraventricular tumor showing
      neuronal differentiation in which repeated recurrences following surgery have
      revealed evidence of increasing nuclear pleomorphism, mitotic activity and glial
      differentiation. We suggest that this tumor broadens further the clinical and
      pathological spectrum of central neurocytoma.

PMID- 9625306
TI  - Clear cell meningioma variant and clinical aggressiveness.
AB  - The few reports about clear cell meningiomas (CCM) point to an inordinate
      clinical aggressiveness despite their histological benignity. We studied 5 CCM
      aiming to assess their clinicopathological, cytometric, and ultrastructural
      features. Two patients were females and 3 males, with a mean age of 36 years. Two
      tumors were spinal, one of the cerebral convexity, one of the tentorium-clinoid
      region, and one of the base of the skull. The first 3 were totally removed and
      have not recurred for a mean follow-up time of 40 months. The tentorium-clinoid
      and the skull base tumors had radical subtotal and partial resections, and
      recurred after 16 and 1.5 months, respectively. All tumors but one, a non
      recurrent one, presented no signs of histological anaplasia. The proliferative
      capacity, as assessed by MIB-1 staining index (SI), of recurrent tumors was
      slightly higher than that of those tumors that did not recur. All cases showed
      DNA diploid pattern. Amianthoid-type fibers were disclosed on ultrastructural
      study. CCM arose in patients younger than those with other variants of
      meningioma, the spinal canal and the posterior fossa were the common sites.
      Finally, intracranial tumors were linked to an aggressive behavior.

PMID- 9625307
TI  - Outbreak of enterically-transmitted hepatitis due to hepatitis A and hepatitis E
      viruses.
AB  - BACKGROUND/AIMS: One hundred and eleven patients with acute hepatitis and 61
      controls were investigated for hepatitis serological markers in order to
      determine the viral etiology of cases involved in a waterborne epidemic of
      hepatitis observed in 1993 in Djibouti, Republic of Djibouti (East Africa). These
      cases occurred both in indigenous Djiboutians, and in French soldiers and their
      families in Djibouti. A retrospective study of the viral etiology of acute
      hepatitis cases observed in French soldiers and relatives living in Djibouti
      during the 3-year period preceding the epidemic was also undertaken. METHODS:
      HAV, HBV and HCV infections were investigated using commercial ELISA tests. HEV
      infections were investigated by testing IgG and IgM-specific antibodies by means
      of three different ELISA tests using recombinant proteins or synthetic peptides.
      RESULTS: Hepatitis A was observed in 37 (33%) and hepatitis E in 43 (39%) of the
      111 cases of acute hepatitis recorded during this epidemic. Hepatitis B
      represented only 6% of the indigenous cases and hepatitis C was not observed
      among the cases investigated. Anti-HEV IgG antibodies were also detected in 19%
      of the indigenous control group. CONCLUSION: These results suggest that both HAV
      and HEV were responsible for this waterborne epidemic of acute hepatitis.
      However, HAV and HEV infections were not equally distributed between French
      expatriates and Djibouti residents. Whereas HAV infections were mainly observed
      in French patients, HEV was almost exclusively found in indigenous patients. This
      study reports for the first time a waterborne outbreak of acute hepatitis
      simultaneously due to HAV and HEV.

PMID- 9625308
TI  - Time course of total cysteine, glutathione and homocysteine in plasma of patients
      with chronic hepatitis C treated with interferon-alpha with and without
      supplementation with N-acetylcysteine.
AB  - BACKGROUND/AIMS: Glutathione depletion might be one reason for the low rate of
      response of patients with chronic hepatitis C to treatment with interferon. The
      aim of the present study was to document the thiol status of patients with
      chronic hepatitis C and the effects of N-acetylcysteine, a precursor for
      glutathione synthesis, on the concentrations of total cysteine, glutathione and
      homocysteine during treatment of chronic hepatitis C with interferon. METHODS:
      Total cysteine, glutathione and homocysteine in plasma were measured by high
      performance liquid chromatography, following reduction of disulfides and
      derivatization of thiols with monobromobimane in a group of 36 patients with
      chronic hepatitis C, who participated in a multicenter, double-blind, randomized,
      placebo-controlled clinical trial studying the effect of supplementation with N
      acetylcysteine (600 mg three times daily) on the response to treatment with
      interferon-a (3 MU three times per week) for 6 months. RESULTS: The
      concentrations of total cysteine (367.0+/-43.9 vs 360.4+/-33.5 nmol/ml, mean+/
      95% confidence interval), glutathione (12.5+/-1.6 vs 14.1+/-1.3 nmol/ml) and
      homocysteine (21.2+/-4.5 vs 19.6+/-5.2 nmol/ml) were similar in patients with
      chronic hepatitis C and healthy control subjects Supplementation with N
      acetylcysteine resulted in measurable concentrations of N-acetylcysteine in
      plasma, but did not significantly increase the concentrations of cysteine,
      glutathione or homocysteine. There was no difference between the two treatment
      groups with regard to transaminases and clearance of HCV RNA. CONCLUSIONS:
      Circulating concentrations of total cysteine, glutathione and homocysteine are
      normal in patients with chronic hepatitis C. Supplementation with N
      acetylcysteine did not increase the circulating concentrations of total cysteine,
      glutathione and homocysteine.

PMID- 9625309
TI  - Early development of chronic active hepatitis in recurrent hepatitis C virus
      infection after liver transplantation: association with treatment of rejection.
AB  - BACKGROUND/AIMS: We retrospectively studied 63 consecutive patients (mean age
      54+/-8) with hepatitis C virus genotype 1b recurrence after liver transplantation
      and with a minimum histological follow-up of 1 year, in order to determine
      whether an early severe recurrence, defined as the development of chronic active
      hepatitis within the first 2 years post-liver transplantation, was associated
      with increased immunosuppression. METHODS: The 1st year immunosuppression data
      (rejection episodes, boluses of methyl-prednisolone, cumulative doses of
      prednisone and azathioprine, OKT3 use) were recorded, and evaluated as predictive
      of severe recurrence at 1 and 2 years post-liver transplantation. Chronic active
      hepatitis and rejection were defined by histological criteria. Immunosuppression
      consisted of cyclosporine, azathioprine and prednisone. The treatment of
      rejection was based on a "bolus" of 1 g methyl-prednisolone/3 days. RESULTS: At 1
      year, 64% (40/63) of the patients had chronic active hepatitis, whereas of the 40
      patients who had a 2nd year biopsy available, 75% had chronic active hepatitis at
      2 years. At 1 year post-liver transplantation, no significant association was
      observed between immunosuppression and the development of chronic active
      hepatitis. In contrast, at 2 years, rejection (p=0.006), treatment of rejection
      (p=0.05), methyl-prednisolone boluses (p=0.013) and the number of rejection
      episodes (p=0.0034) occurring during the 1st year post-liver transplantation were
      significantly more common in patients with chronic active hepatitis. There was
      also a trend towards higher cumulative steroids (9447+/-3176.5 vs 7891.5+/-2111
      mg) and higher cumulative azathioprine doses (13472+/-11154 vs 6233.5+/-5937 mg)
      in patients with chronic active hepatitis as compared to those who did not
      develop chronic active hepatitis. CONCLUSIONS: Rejection and/or its treatment may
      accelerate the natural history of hepatitis C virus genotype 1b infection post
      liver transplantation.

PMID- 9625310
TI  - Chronic hepatitis in children after liver transplantation: role of hepatitis C
      virus and hepatitis G virus infections.
AB  - BACKGROUND/AIMS: Chronic graft hepatitis occurs in 20-30% adults after liver
      transplantation but the prevalence and causes in children are not known. In
      adults, hepatitis C virus infection is prevalent prior to transplantation and
      recurrent infection is a frequent cause of graft dysfunction. The significance of
      the recently described hepatitis G virus infection remains unproven. The aim of
      this study was to examine the role of hepatitis C virus and hepatitis G virus
      infection in chronic graft hepatitis after paediatric liver transplantation.
      METHODS: The prevalence of graft hepatitis and the role of hepatitis C virus and
      hepatitis G virus infections in 80 children after liver transplantation have been
      studied, with a median follow up of 4.4 years (range 0.4 to 10.7), and the
      persistence of hepatitis G infection in the presence of immunosuppression has
      been determined. RESULTS: Chronic graft hepatitis was diagnosed in 19/80 (24%)
      children and was most frequently seen in children transplanted for cryptogenic
      cirrhosis (71%). There was no significant difference in the prevalence of chronic
      hepatitis in those transplanted before or after donor anti-HCV screening.
      Hepatitis C infection occurred in three children transplanted prior to donor
      screening but in only one was associated with chronic hepatitis. Hepatitis G
      infection was found in 22/79 (28%) transplant recipients but was not associated
      with graft hepatitis. In 17/21 children hepatitis G infection persisted for a
      median of 5.2 years after transplantation. CONCLUSION: Chronic hepatitis occurred
      in 24% of children after liver transplantation, a similar prevalence to that in
      adults. Cryptogenic liver disease predisposed to graft hepatitis, but neither
      hepatitis C nor hepatitis G infection was associated. Hepatitis G virus caused a
      frequent and usually persistent infection after transplantation.

PMID- 9625311
TI  - Increased interleukin-12 serum levels in chronic alcoholism.
AB  - BACKGROUND/AIMS: In the present study the serum levels of interleukin-12 were
      analyzed in alcoholic patients in order to explore the possible relationship
      between them and both the ethanol intake status and the existence of alcoholic
      liver disease. METHODS: For that purpose interleukin-12 levels were analyzed in a
      total of 26 alcoholic patients. Additionally, both interferon-gamma and
      interleukin-4 serum levels were measured in the same patients as a means of
      exploring the balance between the T-helper-1 and T-helper-2 immune responses. All
      patients had consumed at least 90 g of ethanol per day for more than 5 years.
      Fourteen were alcoholics without liver disease (AWLD group) and the other 12
      patients were diagnosed as having alcoholic liver cirrhosis. In parallel to the
      patients, 10 age- and sex-matched healthy volunteers were included in the study.
      RESULTS: Our results show that interleukin-12 serum levels are significantly
      increased in AWLD patients as compared to normal controls (p<0.05). In patients
      with cirrhosis, interleukin-12 serum levels varied, depending on the ethanol
      intake status at the time of evaluation. Accordingly, as compared to normal
      controls, significantly increased concentrations of serum interleukin-12 were
      found in the alcoholic liver cirrhosis patients with active ethanol intake (ALCET
      group) (p<0.01), while in the cirrhotic individuals with at least 1 year of
      alcohol withdrawal interleukin-12 serum levels remained within the normal range.
      Only the cirrhotic patients had increased interferon-gamma serum levels. Among
      them, the highest levels were found for individuals from the ALCET group, the
      differences with respect to the healthy subjects being close to statistical
      significance (p=0.05). No significant differences were detected regarding
      interleukin-4 serum levels for any of the groups of patients analyzed compared to
      the control individuals. CONCLUSIONS: Our results show the existence of a
      relationship between ethanol intake and increased interleukin-12 serum levels,
      suggesting that this cytokine may play an important role in the induction of the
      immunological abnormalities found in chronic alcoholism, independently of whether
      or not alcoholic liver disease is present.

PMID- 9625312
TI  - Plasma levels of soluble tumor necrosis factor receptors p55 and p75 in patients
      with alcoholic liver disease of increasing severity.
AB  - BACKGROUND/AIMS: Correlations between serum levels of soluble tumor necrosis
      factor receptors p55 (TNFsRp55) and Child Pugh index have previously been
      reported in alcoholic patients with cirrhosis. We have undertaken this study to
      improve understanding of the role of tumor necrosis factor soluble receptors
      (TNFsRs) in alcoholic liver disease. METHODS: One hundred and two patients with
      alcoholic liver disease of various severity (23 pure steatosis, 22 fibrosis,
      seven acute alcoholic hepatitis without cirrhosis, 12 cirrhosis without acute
      alcoholic hepatitis, 14 cirrhosis with mild acute alcoholic hepatitis and 24
      cirrhosis with severe acute alcoholic hepatitis) were studied. Blood was
      collected on EDTA and plasma was tested for TNFsR concentrations using ELISA
      assays. RESULTS: Plasma levels of TNFsRp55 and p75 increased progressively with
      the severity of liver disease, reaching a maximum in cirrhotic patients with
      severe acute alcoholic hepatitis. Plasma levels of TNFsRp55 in patients with
      fibrosis and of TNFsRp75 in patients with acute alcoholic hepatitis without
      cirrhosis were already higher than in healthy controls. In cirrhotic patients
      with or without acute alcoholic hepatitis TNFsRp55 and p75 were significantly
      increased compared with controls. In cirrhotic patients, plasma levels of
      TNFsRp55 correlated positively with all parameters of liver injury, whereas the
      TNFsRp75/ TNFsRp55 ratio correlated negatively. In cirrhotic patients with severe
      acute alcoholic hepatitis, the TNFsRp75/TNFsRp55 ratio was significantly lower
      than in all other groups. In cirrhotic patients with severe acute alcoholic
      hepatitis treated by prednisolone, the decrease in TNFsRp55 plasma levels between
      day 1 and day 15 was significantly more important in patients still alive at 2
      months than in patients who died within 2 months. CONCLUSIONS: These results show
      that the expression of TNF-soluble receptors (TNFsRs) participates in the early
      phases of the alcoholic liver disease and that the TNFsRp75/TNFsRp55 ratio and
      plasma levels of TNFsRp55 may help to determine the diagnosis and the prognosis
      of severe acute alcoholic hepatitis in cirrhotics.

PMID- 9625313
TI  - Dual-energy CT in the diagnosis and quantification of fatty liver: limited
      clinical value in comparison to ultrasound scan and single-energy CT, with
      special reference to iron overload.
AB  - BACKGROUND/AIMS: It has been suggested that dual-energy CT could differentiate
      irregular fatty liver from other hypodense lesions. We compared dual-energy CT to
      ultrasound scan and single-energy CT in the diagnosis and quantification of fatty
      liver, with special reference to iron overload. METHODS: Twenty-seven patients
      were included according to ultrasound: fatty liver (n=16) and normal liver
      (n=11). Single and dual-energy CT were performed. Attenuation measurements of
      hepatic lobes and control tissues were taken at 140 kV and 80 kV CT-guided liver
      biopsy was done in fatty liver patients, the degree of infiltration was
      estimated, and the histologic iron overload determined (iron overload, n=11; iron
      free, n=5). RESULTS: The mean changes in attenuation for the right hepatic lobe
      were: normal liver: -0.8 (ns); iron overloaded fatty liver: 1.5 (ns); and iron
      free fatty liver: 7.7 (p<0.0053). A spleen-liver attenuation differential
      threshold of 12H (140 kV, single-energy CT) and a right hepatic lobe 140 kV to 80
      kV attenuation differential threshold of 9 H (dual-energy CT) were specific for
      fatty liver. Histology confirmed all cases of fatty liver diagnosed by
      ultrasound, independently of iron overload. Ultrasound did not differentiate
      cases of irregular from diffuse fatty liver detected on CT. Iron overload
      produced a masking effect in CT, decreasing its sensitivity: fatty liver was
      diagnosed in 67% of cases by single-energy CT and in 20% by dual-energy CT.
      Degree of fatty infiltration correlated with single-energy CT. CONCLUSIONS:
      Ultrasound diagnosed fatty liver best. Single-energy CT quantifies fatty
      infiltration, and best differentiates the irregular from the diffuse forms. Dual
      energy CT is limited by poor sensitivity, especially in iron overload.

PMID- 9625314
TI  - Activation of mitogen-activated protein kinases and IL-6 release in response to
      lipopolysaccharides in Kupffer cells is modulated by anisoosmolarity.
AB  - BACKGROUND/AIMS: The influence of anisoosmolarity on the activation of the
      extracellular signal-regulated kinases-1 and -2 and on interleukin-6 release was
      studied in lipopolysaccharide-stimulated rat liver macrophages. METHODS:
      Experiments were performed with rat liver macrophages. Activation of the
      extracellular signal-regulated kinases was determined by kinase shift assay and
      immune complex kinase assay. Interleukin-6 mRNA was measured by Northern blot
      analysis and interleukin-6 production by enzyme-linked immunosorbent assay.
      RESULTS: Lipopolysaccharide-induced activation of the extracellular signal
      regulated kinases-1 and -2 was enhanced in hypoosmotic media (205 mosm/l) and
      diminished by hyperosmotic (405 mosm/l) exposure when compared to normoosmotic
      (305 mosm/l) conditions. These effects were paralleled by changes in
      lipopolysaccharide-stimulated interleukin-6 mRNA expression, when determined
      after 4 h and interleukin-6 release after 18 h. The mitogen-activated protein
      kinase-kinase inhibitor PD 098059 abolished phosphorylation of the extracellular
      signal-regulated kinases-1 and -2 in response to lipopolysaccharide, irrespective
      of the medium osmolarity, and diminished lipopolysaccharide-induced interleukin-6
      mRNA expression and interleukin-6 production under normo- and hypoosmotic
      conditions by about 50%; it also resulted under hyperosmotic conditions in an
      about 80% inhibition. SB 203580, a specific inhibitor of p38 largely abolished
      interleukin-6 mRNA expression and interleukin-6 production, irrespective of
      medium osmolarity, whereas phosphorylation of the extracellular signal-regulated
      kinases was not affected. CONCLUSIONS: The data indicate a modulation of
      lipopolysaccharide-induced interleukin-6 production by ambient osmolarity and an
      involvement of both p38 and the extracellular signal-regulated kinases-1 and -2
      in the stimulation of interleukin-6 production by lipopolysaccharide.

PMID- 9625315
TI  - Transforming growth factor-beta1 in autoimmune hepatitis: correlation of liver
      tissue expression and serum levels with disease activity.
AB  - BACKGROUND/AIMS: Transforming growth factor-beta1 (TGF-beta1) is considered the
      most important mediator of hepatic fibrogenesis. At the same time, TGF-beta1 is
      an immunosuppressive cytokine. Development of fibrosis, often rapid, is a
      characteristic of autoimmune hepatitis, as is spontaneous systemic
      immunosuppression. The aim of our study was therefore to define the role of TGF
      beta1 in autoimmune hepatitis. METHODS/RESULTS: Using the MV 1Lu bioassay, we
      found markedly elevated serum levels of TGF-beta1 (median 109 ng/ml) in active
      autoimmune hepatitis, which normalised when patients reached biochemical
      remission following immunosuppressive therapy (median 34 ng/ml; p=0.0001 compared
      to active disease). With a newly established ELISPOT-assay for TGF-beta1
      producing cells, we could exclude an increase in TGF-beta1-producing peripheral
      blood cells as a source of the elevated TGF-beta1. However, by in situ
      hybridisation and immunohistochemistry, we found strong TGF-beta1 expression in
      the inflamed liver. In addition to non-parenchymal and infiltrating cells, many
      hepatocytes showed strong staining for TGF-beta1. TGF-beta1 expression in the
      liver normalised in remission, yet was still somewhat increased in patients with
      biochemical remission but remaining histological disease activity. CONCLUSIONS:
      These results suggest that TGF-beta1 is an important mediator in active
      autoimmune hepatitis. They support the theory that immunosuppressive therapy
      needs to be guided by histology, as prevention of the development of cirrhosis
      presumably requires near complete suppression of TGF-beta1 in the liver; this is
      only found when there is no longer any histological evidence of inflammation.

PMID- 9625316
TI  - Role of glutathione in hepatic bile formation during reperfusion after cold
      ischemia of the rat liver.
AB  - BACKGROUND/AIMS: Liver reperfusion following cold ischemia is frequently
      associated with diminished bile flow in patients undergoing liver
      transplantation. Glutathione is a major determinant of bile-acid independent bile
      flow, and the effects of cold ischemia on biliary glutathione excretion are
      unknown. METHODS: We examined the effects of cold ischemia (University of
      Wisconsin solution (4 degrees C), 24 h) with subsequent reperfusion (100 min) on
      biliary glutathione excretion in a recirculating system. Since glutathione might
      represent an important antioxidant within the biliary tract and oxidative stress
      in the biliary tract during reperfusion could contribute to the pathogenesis of
      bile duct injury after liver transplantation, we also assessed bile duct
      morphology in reperfused livers of mutant TR- -rats, in whom biliary excretion of
      glutathione is already impaired. RESULTS: Hepatic bile formation was diminished
      in reperfused Wistar rat livers after cold ischemia. Biliary glutathione
      concentrations and output were significantly decreased and correlated with
      postischemic changes in bile secretion. An increased biliary oxidized
      glutathione/glutathione ratio, indicating oxidative stress, was detected only
      immediately after the onset of reperfusion. Basal bile flow rates in TR- -rat
      livers which were already markedly reduced in control-perfused livers, decreased
      further during the early but not the later reperfusion period. Reperfusion of
      both Wistar and TR- -rat livers was not associated with electron microscopic
      evidence of bile duct damage. CONCLUSIONS: We conclude that impaired biliary
      excretion of glutathione contributes to decreased bile flow after cold ischemia.
      The absence of biliary glutathione does not appear to promote ultrastructural
      evidence of bile duct injury during reperfusion in the isolated perfused rat
      liver.

PMID- 9625317
TI  - No evidence for involvement of the interleukin-10 -592 promoter polymorphism in
      genetic susceptibility to primary biliary cirrhosis.
AB  - BACKGROUND/AIMS: Primary biliary cirrhosis is a chronic cholestatic liver disease
      with an autoimmune aetiology. Family studies, which have shown a significantly
      increased incidence of primary biliary cirrhosis in the close relatives of
      patients, suggest that genetic factors play a significant role in determining
      disease susceptibility. Several studies have previously identified loci which
      appear to play a role in determining this susceptibility, including the MHC class
      II allele HLA DR8, and the class III encoded C4A null allele (C4AQ0). Here, we
      have studied another candidate susceptibility locus in primary biliary cirrhosis,
      an apparently functional biallelic polymorphism at position -592 in the promoter
      region of the gene encoding the immuno-modulatory cytokine interleukin-10.
      Interleukin-10 plays an important role in the functional control, in vivo, of
      autoreactive Th-1 type CD4+ T-cells, with experimental manipulation of
      interleukin-10 leading to significant modulation of disease development in animal
      models of autoimmunity. METHODS: Interleukin-10 -592 genotypes were studied by
      polymerase chain reaction in 171 well-characterised, histologically-staged,
      primary biliary cirrhosis patients and 141 locally matched controls. RESULTS: Of
      171 primary biliary cirrhosis patients, 99 were homozygous for the commoner
      allele (C/C), 68/171 (40%) were heterozygotes (A/C), whilst 4/171 (2%) were
      homozygous for the rarer allele (A/A). These genotype frequencies were not
      significantly different from those seen in controls (p=0.49, odds ratio 1.2 [0.8
      1.91). CONCLUSIONS: These findings, in the first study of IL-10 as a candidate
      locus in a human autoimmune disease, suggest that IL-10 -592 is not a
      susceptibility locus in primary biliary cirrhosis.

PMID- 9625318
TI  - The antinuclear autoantibodies Sp100 and gp210 persist after orthotopic liver
      transplantation in patients with primary biliary cirrhosis.
AB  - BACKGROUND/AIMS: Primary biliary cirrhosis is an autoimmune liver disease which
      is characterized by the presence of autoantibodies directed against mitochondrial
      components which belong to the pyruvate dehydrogenase enzyme complex. Apart from
      antibodies against mitochondrial components, primary biliary cirrhosis patients
      often show antibodies against nuclear components, of which anti-Sp100 and anti
      gp210 are considered to be disease specific. We investigated the incidence and
      course of antibodies against nuclear components in primary biliary cirrhosis
      patients before and after liver transplantation. METHODS: Sera from 42 primary
      biliary cirrhosis patients were studied using indirect immunofluorescence to
      detect antibodies against mitochondrial components and antibodies against nuclear
      components, ELISA to detect anti-Sp100, and immunoblot analysis to detect anti
      gp210 and antibodies against nuclear components subtypes. RESULTS: Ninety-three
      percent of primary biliary cirrhosis patients in our study were antimitochondrial
      antibody positive. Forty-three percent of the patients were antinuclear antibody
      positive. Of these, 35% had antibodies against Sp100 and 36% were positive for
      anti-gp210. After transplantation, antimitochondrial antibody titers as well as
      antinuclear antibody titers decreased in all patients. Autoantibodies in low
      titer persisted for up to 13 years. The pattern of nuclear autoantigens
      recognized by patient sera was unchanged after liver transplantation. However,
      the antinuclear antibody pattern was very different between the individual
      patients. Anti-Sp100 and anti-gp210 were not detected in sera of patients with
      autoimmune hepatitis, hepatitis C infection, inflammatory bowel disease,
      connective tissue diseases, or primary sclerosing cholangitis. The serum alkaline
      phosphatase level was not different in antinuclear antibody negative or positive
      patients before or after transplantation. CONCLUSIONS: We conclude that the
      persistence of antibodies against mitochondrial components, and anti-Sp100 and
      anti-gp210 in primary biliary cirrhosis patients after liver transplantation is
      disease specific, but that this does not reflect recurrent disease activity in
      the graft.

PMID- 9625319
TI  - Beneficial effect of ursodeoxycholic acid on alterations induced by cholestasis
      of pregnancy in bile acid transport across the human placenta.
AB  - BACKGROUND/AIMS: The existence of impairment in bile acid transport across the
      placenta during intrahepatic cholestasis of pregnancy and the effect of
      ursodeoxycholic acid treatment (1 g/day) were investigated. METHODS: Kinetic
      parameters were calculated from experiments carried out on membrane vesicles
      obtained from basal (TPMb, fetal-facing) and apical (TPMa, maternal-facing)
      trophoblast plasma membranes. Bile acid uptake was measured using varying
      concentrations of [14C]-glycocholate and a rapid filtration technique. RESULTS:
      The maximal velocity of transport (Vmax), the apparent affinity constant (Kt) and
      the efficiency (Ef) of transport (Vmax/Kt) of the anion:bile acid exchanger
      located at the TPMb were reduced in intrahepatic cholestasis of pregnancy.
      Ursodeoxycholic acid induced a reversal of Vmax, Kt and Ef to normal values.
      Owing to the 3-fold increase in Vmax, with no change in Kt, intrahepatic
      cholestasis of pregnancy induced an enhancement in Ef of ATP-independent bile
      acid transport across TPMa. Both Vmax and Ef were restored to normal values by
      ursodeoxycholic acid. Finally, in ATP-dependent bile acid transport across TPMa,
      a reduction in the Ef due to an increase in Vmax together with a more pronounced
      increase in Kt was found. This impairment was also reversed by ursodeoxycholic
      acid. CONCLUSIONS: These results suggest that placenta bile acid transport
      systems are impaired in intrahepatic cholestasis of pregnancy. Moreover, together
      with the confirmed beneficial effect for intrahepatic cholestasis of pregnancy
      patients, such as the relief of pruritus and the improvement in biochemical
      markers of cholestasis, ursodeoxycholic acid treatment restores the ability of
      the placenta to carry out vectorial bile acid transfer.

PMID- 9625320
TI  - Significance of increased plasma adrenomedullin concentration in patients with
      cirrhosis.
AB  - BACKGROUND/AIMS: Adrenomedullin recently discovered in human pheochromocytoma is
      a potent vasodilatory peptide mainly derived from vascular endothelial and smooth
      muscle cells. Hyperdynamic circulation, ultimately leading to ascites formation,
      has been attributed to peripheral vasodilatation in liver cirrhosis. However,
      little is known about the role of adrenomedullin in this condition. METHODS:
      Plasma adrenomedullin concentrations were measured by radioimmunoassay after
      extraction and purification in 28 cirrhotic patients without ascites, 12
      cirrhotic patients with ascites and 10 healthy subjects. RESULTS: Plasma
      adrenomedullin concentrations in cirrhotic patients with ascites (12.7+/-4.5
      fmol/ml) were significantly higher than those in cirrhotic patients without
      ascites (8.2+/-2.3 fmol/ml, p<0.005) and healthy subjects (5.8+/-0.8 fmol/ml,
      p<0.005). Interestingly, plasma adrenomedullin concentrations were highest in
      patients with refractory ascites (n=5, 15.8+/-3.0 fmol/ml) and were positively
      correlated with the Child-Pugh score (r=0.44, p<0.01). Moreover, plasma
      adrenomedullin concentrations were positively correlated with plasma renin
      activity (r=0.63, p<0.0001), plasma aldosterone (r=0.60, p<0.0001) and plasma
      norepinephrine concentrations (r=0.60, p<0.0001), and negatively correlated with
      creatinine clearance (r=-0.61, p<0.0005) and urinary sodium excretion (r=-0.44,
      p<0.02). Stepwise multiple regression analysis using certain independent
      variables, including Pugh's score, vasoactive substances, renal function and
      hemodynamic parameters, showed that the adjusted R square was highest when plasma
      renin activity and creatinine clearance (standard coefficient=0.53, -0.49,
      respectively) were considered (adjusted R square=0.61, p<0.0001). CONCLUSIONS:
      Plasma adrenomedullin concentrations increased with the progression of liver
      cirrhosis and were highest in cirrhotic patients with refractory ascites. In
      addition, elevated adrenomedullin was associated with activation of the renin
      angiotensin-aldosterone and sympathetic nervous systems, and with functional
      renal impairment in cirrhosis. Considering the potent vasodilatory action of
      adrenomedullin, increased adrenomedullin may participate in the hyperdynamic
      circulation, ultimately leading to ascites formation, in patients with liver
      cirrhosis.

PMID- 9625321
TI  - Noninvasive hemodynamic measurements of superior mesenteric artery in the
      prediction of portal pressure response to propranolol.
AB  - BACKGROUND/AIMS: The portal pressure response to propranolol administration is
      heterogeneous in patients with cirrhosis. The aim of this study was to examine
      the diagnostic accuracy of noninvasive hemodynamic parameters of superior
      mesenteric artery (SMA) and femoral artery (FA) in the prediction of portal
      pressure response to propranolol. METHODS: Twenty-six patients with cirrhosis
      were studied. Portal pressure was assessed by measurements of hepatic venous
      pressure gradient. Mean arterial pressure and heart rate were also recorded.
      Cardiac index, and flow velocity of SMA and FA, and pulsatility index of SMA and
      FA were then measured by means of Doppler ultrasonography. After intravenous
      propranolol administration (0.10 mg/kg), the above measurements were repeated.
      RESULTS: Propranolol significantly reduced cardiac index, heart rate, SMA flow
      velocity, and FA flow velocity and increased SMA pulsatility index and FA
      pulsatility index. Although propranolol significantly decreased hepatic venous
      pressure gradient, a reduction of > or =20% was seen in only 10 patients (good
      responders); the remaining 16 patients exhibited <20% reduction (poor
      responders). No significant differences in clinical and baseline hemodynamic data
      were found in the two groups. There were no also significant differences in
      changes in heart rate and cardiac index. However, reductions in SMA and FA flow
      velocity were significantly greater in good responders than in poor responders.
      Although there was no the increase in FA pulsatility index, the increase in SMA
      pulsatility index was significantly greater in good responders than in poor
      responders. When appropriate cut-off points were determined for these variables,
      overall predictive values of SMA flow velocity (-20%) and SMA pulsatility index
      (+15%) were 91% and 83%, whereas the overall predictive value of FA flow velocity
      (-25%) was only 69%. CONCLUSIONS: These results suggest that SMA flow velocity
      and SMA pulsatility index, but not FA flow velocity and FA pulsatility index, are
      useful noninvasive parameters in the prediction of portal pressure response to
      propranolol administration.

PMID- 9625322
TI  - Oral L-ornithine-L-aspartate therapy of chronic hepatic encephalopathy: results
      of a placebo-controlled double-blind study.
AB  - BACKGROUND/AIMS: In the current state of knowledge of the pathophysiology of
      hepatic encephalopathy, a reduction in hyperammonemia is the most important
      evidence of effective treatment. Therefore, the therapeutic efficacy of oral L
      ornithine-L-aspartate, which improves impaired ammonia detoxification, was
      investigated in patients with cirrhosis, hyperammonemia and stable, overt,
      chronic hepatic encephalopathy, and in subclinical hepatic encephalopathy in a
      randomized, double-blind, placebo-controlled clinical trial. METHODS: Oral L
      ornithine-L-aspartate was administered three times daily at fixed times for 14
      consecutive days in a total dose of 18 g per day. The design was chosen to
      prevent an increase in ammonia induced by a protein meal of 0.25 g/kg body
      weight, given at the start of the daily treatment period. Efficacy variables
      were: fasting and postprandial ammonia concentration, Number-Connection-Test
      time, mental state grades, and a Portosystemic Encephalopathy Index. Analyses
      were based on the total study sample of 32 placebo- and 34 L-ornithine-L
      aspartate-treated patients as well as on the subgroup samples in the overt (20
      placebo- and 23 L-ornithine-L-aspartate-treated) and subclinical hepatic
      encephalopathy (12 placebo- and 11 L-ornithine-L-aspartate-treated) patients.
      RESULTS: Number Connection Test performance times (p<0.01) as well as fasting
      (p<0.01) and postprandial (p<0.05) venous blood ammonia concentrations in the L
      ornithine-L-aspartate-treated group showed improvement in comparison to placebo.
      Also, the mental state grade (p<0.05) and the Portosystemic Encephalopathy Index
      (p<0.01), improved to a much greater degree in the L-ornithine-L-aspartate group
      than in the placebo group. Adverse events were observed in neither the placebo
      nor the L-ornithine-L-aspartate-treated patients. CONCLUSION: Oral L-ornithine-L
      aspartate is a safe, well-tolerated treatment with a good compliance rate and a
      beneficial therapeutic effect in patients with cirrhosis and stable, overt,
      chronic hepatic encephalopathy.

PMID- 9625323
TI  - Importance of hepatic first-pass removal in metastasis of colon carcinoma cells.
AB  - BACKGROUND/AIMS: It might be thought that colon carcinoma tends to metastasize to
      the liver because tumor cells leaving the primary colon tumor pass initially
      through the liver. Therefore we elucidated the kinetics of tumor cells in the
      body in order to understand the effect of the location of the liver on hepatic
      metastasis, that is to examine the hepatic first-pass effect of tumor cells.
      METHODS: Based on a physiological kinetic model, we examined quantitatively the
      hepatic metastasis and hepatic distribution of KM12-H1X cells administered by
      different routes. RESULTS: Both the number and incidence of colonies of hepatic
      metastasis were much greater after intrasplenic injection than after intravenous
      injection. The distribution of radioactivity to the liver after intrasplenic
      injection of [3H] thymidine-labeled cells was also much higher than that after
      intravenous injection. The number of colonies of hepatic metastasis correlated
      well with the area under the curve of the distributed amount of the tumor cells
      in the liver, regardless of the injection route; the correlation line was
      identical for each injection route. CONCLUSIONS: These results suggest that the
      hepatic first-pass effect is an important factor for the hepatic metastasis and
      that the cumulative number of tumor cells distributed in the liver is a
      determining factor for the degree of metastasis. Mathematical analysis based on a
      physiological model also suggests that hepatic metastasis depends on hepatic
      first-pass trapping of tumor cells.

PMID- 9625324
TI  - Mechanism of initial distribution of blood-borne colon carcinoma cells in the
      liver.
AB  - BACKGROUND/AIMS/METHODS: The distribution characteristics of a human colon
      carcinoma cell line, KM12-HX cells, were examined. After intraportal vein
      (i.p.v.) or intravenous (i.v.) injection into rats, almost all the injected tumor
      cells are distributed to liver or lung, respectively, both after 30 s and 30 min.
      Our previous kinetic analysis of the fate of tumor cells revealed that the
      cumulative amount of tumor cells distributed in the liver is a factor determining
      the degree of metastasis. Thus, we examined the mechanism of initial efficient
      trapping of tumor cells by the liver in more detail. RESULTS: Thirty minutes
      after tumor cells were injected into the left ventricle of the heart, the
      distribution of tumor cells was more restricted in several tissues (kidney, small
      intestine, large intestine and spleen), as compared with the distribution of
      microspheres undergoing 100% extraction, indicating that the first-pass
      extraction of KM12-HX cells is incomplete in these organs. The hepatic first-pass
      distribution of these tumor cells was unaffected by pretreatment of liposomes,
      such that the preinjected amount was sufficient to saturate the phagocytotic
      function of macrophages. Thus, the mechanism of initial distribution of the tumor
      cells to the liver is different from the mechanism of liposome uptake by
      macrophages. Considering that the diameter of microvessels in sinusoid and KM12
      HX cells is approximately 7 and 12 microm, respectively, it is possible that
      these tumor cells are trapped physically in hepatic microvessels. In fact, after
      i.p.v. injection of microspheres 5 microm in diameter, only 20% of the dose was
      distributed to liver and the rest to other tissues. In contrast, almost 100% of
      microspheres 10 microm in diameter were distributed to the liver. CONCLUSIONS:
      These results support the hypothesis that the initial organ distribution of blood
      borne tumor cells is determined by mechanical and physical properties of the
      cells.

PMID- 9625325
TI  - Gene therapy for hepatic micrometastasis of murine colon carcinoma.
AB  - BACKGROUNDS/AIMS: Pit cells are located in the hepatic sinusoids and are organ
      associated natural killer cells that contribute to immune surveillance in the
      liver. In the present study, the interleukin-2 gene was introduced into
      hepatocytes using an adenovirus vector to induce interleukin-2 production in an
      attempt to enhance the natural killer activity of pit cells, leading to
      inhibition of metastasis of colon carcinoma. METHODS: The recombinant adenovirus
      vector "Adex1CAmIL2" was constructed by inserting an expression unit which was
      composed of the CAG promotor (cytomegalovirus enhancer plus chicken beta-actin
      promotor), murine interleukin-2 cDNA, and a rabbit beta-globin polyadenylation
      signal. After administration of Adex1CAmIL2 to mice (4x10(7) pfu per animal), the
      expression of murine interleukin-2 in hepatocytes was examined by immunostaining
      and in situ hybridization, and the natural killer activity of hepatic mononuclear
      cells was measured. Inhibition of hepatic metastasis of colon carcinoma was
      examined after infusion of colon 38 tumor cells into the superior mesenteric
      vein. RESULTS: After administration of Adex1CAmIL2, interleukin-2 mRNA expression
      was demonstrated in hepatocytes until day 7, and the serum interleukin-2 level
      was increased. The natural killer activity of hepatic mononuclear cells was
      markedly enhanced for 7-10 days. Hepatic metastasis was inhibited by
      administration of Adex1CAmIL2 until day 7 after tumor cell inoculation.
      CONCLUSION: These results suggest that gene therapy using Adex1CAmIL2 could be
      potentially useful for inhibiting hepatic micrometastasis by enhancing the
      natural killer activity of pit cells.

PMID- 9625326
TI  - Pharmacological treatment of portal hypertension: present and future.

PMID- 9625327
TI  - Images in hepatology. Polycystic echinococcosis by E. vogeli in the Amazon
      region.

PMID- 9625328
TI  - Efficacy of famciclovir treatment in chronic hepatitis B patients with different
      mutations at position 552 of the DNA polymerase gene.

PMID- 9625329
TI  - A randomized controlled trial of interferon-alpha in patients with cirrhosis
      caused by 2a/2b genotype hepatitis C virus.

PMID- 9625330
TI  - Congenital hydrocephalus: nosology and guidelines for clinical approach and
      genetic counselling.
AB  - Congenital hydrocephalus is a serious condition that can arise from multiple
      causes. It comprises a diverse group of conditions which result in impaired
      circulation and absorption of cerebrospinal fluid. Congenital malformations of
      the central nervous system, infections, haemorrhage, trauma, teratogens and,
      occasionally, tumours can all give rise to hydrocephalus. In this paper we focus
      on the genetic aspects of hydrocephalus, excluding neural tube defects. The
      incidence is 0.4-0.8 per 1000 liveborns and stillbirths. X-linked hydrocephalus
      comprises approximately 5% of all cases. This condition is caused by mutations in
      the gene at Xq28 encoding for L1, a neural cell adhesion molecule. Carrier
      detection and prenatal diagnosis can be offered to affected families by means of
      chorionic villus biopsy and linkage analysis or L1 mutation analysis. In general,
      recurrence risk for congenital hydrocephalus excluding X-linked hydrocephalus, is
      low; empiric risk figures found in various studies range from <1% to 4%.
      Unfortunately, prenatal diagnosis based on an early ultrasound scan is not always
      reliable as ventriculomegaly usually starts after 20 weeks of gestation. We
      stress the importance of additional clinical investigations. Prognosis in the
      prenatally diagnosed patients depends on additional malformations but in general,
      is not very good. CONCLUSION: Congenital hydrocephalus may be non-syndromic and
      syndromic. Prognosis depends primarily on the underlying cause and/or associated
      malformations, which have to be delineated on the basis of clinical, cytogenetic
      and molecular analysis.

PMID- 9625332
TI  - Treatment with human growth hormone in patients with Prader-Labhart-Willi
      syndrome reduces body fat and increases muscle mass and physical performance.
AB  - Twelve children with documented Prader-Labhart-Willi syndrome were treated with
      human growth hormone (24 U/m2/week) during 1 year. The children were divided into
      three groups: group 1: overweight and prepubertal (n=6, age 3.8-7.0 years); group
      2: underweight and prepubertal (n=3, age 0.6-4.1 years); group 3: pubertal (n=3,
      age 9.2-14.6 years). In group 1, height increased from -1.7 SD to -0.6 SD, while
      weight decreased from 1.1 SD to 0.4 SD, with a dramatic drop in weight for height
      from 3.8 SD to 1.2 SD. Hand length increased from -1.5 SD to -0.4 SD and foot
      length from -2.5 SD to -1.4 SD. Body fat, measured by dual X-ray energy
      absorptiometry, dropped by a third, whereas muscle mass increased by a fourth.
      Physical capability (Wingate test) improved considerably. The children were
      reported to be much more active and capable. In group 2, similar changes were
      seen, but weight for height increased, probably because muscle mass increase
      exceeded fat mass decrease. Changes in group 3 were similar as in group 1, even
      though far less distinct. CONCLUSION: Growth hormone treatment in Prader-Labhart
      Willi syndrome led to dramatic changes: distinct increase in growth velocity,
      height and muscle mass, as well as an improvement in physical performance. Fat
      mass and weight for height decreased in the initially overweight children, and
      weight for height increased in underweight children.

PMID- 9625331
TI  - Effect of central precocious puberty and gonadotropin-releasing hormone analogue
      treatment on peak bone mass and final height in females.
AB  - To evaluate the effect of central precocious puberty (CPP) and its treatment with
      gonadotropin-releasing hormone (GnRH) analogues on final height and peak bone
      mass (PBM), we measured lumbar bone mineral density (BMD) in 23 girls at final
      height. Patients were distributed in two groups. Group 1: 14 patients with
      progressive CPP were treated with GnRH analogues; seven patients received
      buserelin (1600 microg/daily), subsequently switched to depot triptorelin (60
      microg/kg/26-28 days); seven patients were treated with depot triptorelin (60
      microg/kg/26-28 days); mean age of treatment was 6.2 years (range 2.7-7.8 years);
      the treatment was discontinued at the mean age of 10.1 years (range 8.7-11.3
      years); final height was reached at the mean age 13.4 years (range 12.0-14.9
      years). Group 2: 9 patients (mean age 6.5 years, range 4.8-7.7 years) with a
      slowly progressing variant of CPP were followed without treatment; final height
      was reached at the mean age 13.6 years (range 12.5-14.8 years). Lumbar BMD (L2-L4
      by dual energy X-ray absorptiometry) was measured in all patients at final
      height. In group 1, final height (158.9+/-5.4 cm) was significantly greater than
      the pre-treatment predicted height (153.5+/-7.2 cm, P < 0.001), but significantly
      lower than mid-parental height (163.2+/-6.2 cm, P < 0.005). Subdividing the girls
      of group 1 according to the bone age at discontinuation of therapy (i.e. < or
      =11.5 years, n=5, or > or =12.0 years, n=9), the former patients had a final
      height significantly higher than the latter (163.7+/-3.9 cm vs 156.5+/-4.6 cm, P
      < 0.02). In group 2, final height (161.8+/-4.6 cm) was similar to the pre
      treatment predicted height (163.1+/-6.2 cm, P=NS) and was not significantly
      different from mid-parental height (161.0+/-5.9 cm). BMD values (group 1: 1.11+/
      0.14 g/cm2, group 2: 1.22+/-0.08 g/cm2) were not significantly different from
      those of a control group (1.18+/-0.10 g/cm; n=20, age 16.3-20.5 years) and the
      patients' mothers (group 1: 1.16+/-0.07 g/cm2, n=11, age 32.9-45.1 years; group
      2: 1.20+/-0.08 g/cm2, n=7, age 33.5-46.5 years). In group 1, the girls who
      stopped therapy at a bone age < or =11.5 years had significantly higher BMD
      (1.22+/-0.10 g/cm2) compared to those who discontinued therapy at a bone age > or
      =12.0 years (1.04+/-0.12 g/ cm2, P < 0.05). CONCLUSION: In girls with progressive
      CPP, long-term treatment with GnRH analogues improves final height. A subset of
      patients with CPP does not require treatment because good statural outcome
      (slowly progressing variant). In CPP, the abnormal onset of puberty and the long
      term GnRH analogue treatment do not impair the achievement of PBM. In GnRH
      treated patients, the discontinuation of therapy at an appropriate bone age for
      pubertal onset may improve both final height and PBM.

PMID- 9625333
TI  - Mutation THR-185 ILE is associated with corticosterone methyl oxidase deficiency
      type II.
AB  - Two boys presenting with infection-triggered, life-threatening salt-loss and
      hyperkalaemia were published in 1991 in the European Journal of Pediatrics. In
      both boys, the diagnosis of corticosterone methyl oxidase (CMO) deficiency type
      II has been established on the basis of determinations of plasma and urinary
      steroids. We had the opportunity to perform a molecular genetic study in one of
      the two boys. This boy had an elevated plasma 18
      hydroxycorticosterone/aldosterone ratio which is pathognomonic for CMO deficiency
      type II. Sequence analysis of the CYP11B2 gene revealed a homozygous single base
      exchange in codon 185 of CYP11B2 causing an amino acid substitution Thr185Ile.
      CONCLUSION: A Thr185Ile mutation in the CYP11B2 gene was found in a patient with
      CMO deficiency type II. This mutation may change the secondary structure of the
      enzyme leading to its decreased activity.

PMID- 9625334
TI  - Safety and efficacy of interferon retreatment in children with chronic hepatitis
      B.
AB  - More than 50% of children with chronic hepatitis B do not respond to treatment
      with alpha-interferon. Since these patients continue to display high viral
      replication and progressive liver disease, retreatment should be considered. To
      date it has not been well evaluated whether a second course of treatment could
      increase the response rate. In two alpha-interferon retreatment trials in adult
      patients the response rate, defined by seroconversion from HBeAg to anti-HBe,
      ranged between 11% and 44%. One beta-interferon retreatment study in children
      reported a seroconversion rate of 32%. Regrettably, none of the studies included
      a control group observing the 'spontaneous' seroconversion rate after a first
      interferon cycle. Thus, a nonrandomized alpha-interferon retreatment study in
      children including control patients was performed. Alpha-interferon for
      retreatment was administered 3 times a week for 16-24 weeks in 15 children (5-16
      years) at least 6 months after ceasing the first cycle. Four children received 5
      MU/m2 of a natural alpha-interferon and 11 children 9 MU/m2 recombinant alpha
      interferon 2b. Follow up was 18-47 months after initial treatment. In parallel, a
      control group of 19 unretreated children with comparable clinical and demographic
      data was followed for 12-39 months. HBeAg seroconversion was observed in 5 (33%)
      of the retreated children and in 5 (26%) of the control patients during follow
      up. The difference is not significant. In the initially nonresponding children,
      those with high ALT levels before the first treatment showed late HBeAg
      seroconversion more frequently than those with low ALT levels (P=0.017)
      irrespective of retreatment. The ALT level before retreatment was not a predictor
      for response. CONCLUSIONS: A second cycle of alpha-interferon during the 3 years
      following the first treatment in nonresponding children with chronic hepatitis B
      can be safely performed but did not increase HBeAg/anti-HBe seroconversion
      compared with the spontaneous seroconversion rate of patients without
      retreatment.

PMID- 9625335
TI  - Diagnosis of the first Japanese patient with 3-oxo-delta4-steroid 5beta-reductase
      deficiency by use of immunoblot analysis.
AB  - A 3-oxo-delta4-steroid 5beta-reductase (5beta-reductase) deficiency is difficult
      to diagnose because severe liver damage can result in a similar pattern of
      metabolite excretion. We investigated the usefulness of immunoblot analysis for
      diagnosis of 5beta-reductase deficiency and quantitatively analysed urinary bile
      acids by gas chromatography-mass spectrometry in a 5-month-old Japanese boy with
      severe neonatal cholestasis associated with hypertyrosinaemia. A liver sample was
      examined by immunoblot analysis using monoclonal antibodies against 5beta
      reductase. Urinary 3-oxo-delta4 bile acids accounted for 88.3% of total bile
      acids, 5alpha-bile acids for 0.9%, and primary bile acids for 9.1%. Immunoblot
      analysis of the liver tissue showed an indistinct band of 5beta-reductase.
      CONCLUSIONS: These findings suggest that this patient had a secondary 5beta
      reductase deficiency due to severe liver damage, even though 3-oxo-delta4 bile
      acids constituted more than 70% of total urinary bile acids. However, the patient
      may possibly have had an inherited 5beta-reductase deficiency.

PMID- 9625336
TI  - Factors influencing the spread of pertussis in households.
AB  - The objective of this study was to compare the spread of pertussis in children
      and adults being secondary contacts after household exposure. The study was
      nested in an efficacy trial of an acellular pertussis vaccine. The spread of the
      disease was also monitored with respect to gender and antibiotic therapy. A total
      of 453 index cases, of which 133 were monitored for adult disease, fulfilled the
      WHO definition of pertussis. They had contacts to 173 unvaccinated children aged
      6-47 months, and a total of 101 adults with pertussis were followed. Detection of
      the bacteria, or a significant increase of specific antibodies confirmed the
      diagnosis. Secondary spread of the disease was assumed, when a household member
      coughed for 7 days or more and had laboratory evidence for pertussis. Crude
      attack rates (AR) were 69% in children and 31% in adults (P < 0.05). AR in
      children were independent of gender but more women than men (P=0.02) were
      affected in those households where the index case was a child. Erythromycin
      treatment of the index case reduced the AR in exposed toddlers from 80% to 57%
      (P=0.06), and in exposed adults from 40% to 21% (P=0.2). Erythromycin therapy in
      contacts did not alter the clinical course of the disease significantly.
      CONCLUSIONS: In a household study of pertussis, 69% of children and 31% of adults
      (more women than men) contracted the disease. Erythromycin reduced the number of
      infections in household contacts, but did not alter the clinical course in those
      who contracted pertussis.

PMID- 9625337
TI  - Economic evaluation of pertussis prevention by whole-cell and acellular vaccine
      in Germany.
AB  - Acellular pertussis vaccines are less reactogenic than whole cell pertussis
      vaccines, but they are also more expensive. Based on simulation models, we
      compared the costs and effects of three alternative pertussis vaccination
      strategies in German children to "no prevention": (1) vaccination with whole-cell
      vaccine at 45% coverage (vaccine efficacy 90%), (2) vaccination with acellular
      vaccine at 45% coverage (vaccine efficacy 85%), and (3) vaccination with
      acellular vaccine at 90% coverage. In the two low coverage scenarios expected
      annual savings in direct medical costs through prevention of disease were larger
      for whole-cell than for acellular vaccination (252 vs 216 million DM,
      respectively). Direct costs for treating the more important adverse events
      induced by whole-cell vaccination (16.9 million DM annually) did not outweigh the
      higher direct costs of pertussis infections not prevented with the acellular
      vaccine and the higher price of the acellular vaccine. However, vaccination with
      acellular pertussis vaccine rapidly becomes as cost saving as vaccination with
      whole-cell vaccine as soon as vaccination coverage can be raised from 45% to
      52.5% with acellular vaccine. Acellular vaccination is also the superior
      alternative when considering indirect cost savings resulting from reduction in
      work-loss due to adverse events. CONCLUSION: In our simulations, the most cost
      effective pertussis prevention strategy was the use of an effective whole-cell
      vaccine with a high coverage rate. Introduction of the more expensive acellular
      pertussis vaccines becomes cost saving if at least a 7.5% increase in coverage is
      achieved. If also non-medical indirect costs to parents resulting from vaccine
      associated side-effects are accounted for, acellular vaccines may be more cost
      effective also in countries with already high whole-cell vaccine coverage.

PMID- 9625338
TI  - Pyostomatitis vegetans in childhood.
AB  - Pyostomatitis vegetans is an oral eruption, characterized by small pustules,
      ulcers and erythematous vegetations of the labial and buccal mucosae as well as
      labial-attached gingivae. Its importance lies in its high correlation with
      inflammatory bowel disease. It is commonly associated with skin and inflammatory
      bowel disease and is rare in children. We here report a sister and brother with
      onset of the disease at the age of 5 and 7 years, respectively. It is the first
      report of familial pyostomatitis vegetans occurring in the youngest patients
      hitherto reported. CONCLUSION: The observation of two sibs with pyostomatitis,
      vegetans pyoderma gangrenosum and inflammatory bowel disease suggest a hereditary
      disposition to this rare triad.

PMID- 9625339
TI  - Comparison of the effects of theophylline and caffeine on serum erythropoietin
      concentration in premature infants.
AB  - Theophylline administration has been shown to attenuate erythropoietin (EP)
      production in adults; the effect of caffeine is not known. Our aim was to
      determine whether caffeine and theophylline had similar effects on EP production
      in the premature newborn. If caffeine was found to have a greater effect, this
      would influence prescribing habits. Fifty preterm infants (mean gestational age
      28 weeks) who had clinically significant apnoea were randomized to receive
      theophylline (4 mg/kg then 2 mg/kg twice daily) or caffeine (10 mg/kg then 2.5
      mg/kg once daily). The methylxanthines were continued at least until discharge
      from the NICU and the dosage altered to keep the levels within the therapeutic
      range. As an assessment of EP production, serum EP concentrations were measured.
      Blood for EP, haemoglobin, reticulocyte count, theophylline and caffeine levels
      was obtained prior to treatment and at least during weeks 3 and 7. There was no
      significant difference in the mean EP level in the two groups taken prior to
      treatment at a median age of 2 days of life. There were similar falls in
      haematocrit and haemoglobin in the two groups during the study period compared to
      pre-treatment values. At that time, however, the median reticulocyte count was
      higher in the caffeine compared to the theophylline treated infants (P < 0.05).
      This was associated with a rise compared to baseline (median 10.0-0.2 mU/ml) in
      the mean EP levels in the caffeine group and a decrease from a median of 10.1 to
      8.3 mU/ml in the theophylline group, but the EP levels in the two groups at week
      7 did not differ significantly. CONCLUSION: These results suggest that caffeine
      does not have a greater impact than theophylline on EP production.

PMID- 9625340
TI  - Effect of inhaled nitric oxide on intrapulmonary right-to-left-shunting in two
      rabbit models of saline lavage induced surfactant deficiency and meconium
      instillation.
AB  - Marked hypoxia secondary to intrapulmonary right-to-left shunting is a
      characteristic of respiratory failure in human neonates and can sometimes be
      complicated by additional extrapulmonary right-to-left shunting. To investigate
      the effect of inhaled nitric oxide (iNO) on intrapulmonary shunting, two typical
      pulmonary diseases of the newborn (respiratory distress syndrome and meconium
      aspiration) were reproduced in 32 mechanically ventilated rabbits weighing
      approximately 2 kg each. After tracheotomy, catheters were inserted into a
      jugular vein, a carotid artery and the right ventricle (to measure systolic right
      ventricular pressure [SRVP] and mixed venous oxygen content for calculation of
      shunt by Fick equation). Repeated airway lavages (LAV) with normal saline or
      repeated instillations of a suspension of human meconium (MEC) were continued
      until both the a/A-ratio was < or =0.14 and a peak inspiratory pressure > or =22
      mbar was needed to keep the tidal volume constant at 10 ml/kg of body weight.
      Measurements of shunt, SRVP, systolic systemic pressure, physiological dead
      space, tidal volume and a ventilation index were performed before and after
      completion of lung damage and at 20 and 60 min after administering iNO at 80 ppm.
      Four groups of rabbits were studied (n=8 in each group): LAV control and
      intervention, Mec control and intervention. 60 min after starting iNO, there was
      a decrease in shunt (LAV: 67.6%+/-[SD] 11.3% vs 56.2+/-16.4, P=0.05; MEC: 52.6+/
      6.3 vs 44.3+/-8.3, P < 0.05), in SRVP (LAV: 29.7 mmHg +/-10.1 mmHg vs 20.0+/-8.2,
      P < 0.01; MEC: 25.1+/-4.4 vs 22.3+/-5.0, P=0.46) and in dead space (% of tidal
      volume, LAV: 32.7%+/-10.5% vs 25.9+/-10.1, P < 0.01; MEC: 26.1+/-16.6 vs 18.9+/
      10.1, P=0.05). These results demonstrate that iNO decreases intrapulmonary shunt
      (as well as SRVP and dead space). We suggest that iNO may be beneficial in human
      newborns with severe respiratory failure even if no extrapulmonary shunting via
      ductus or foramen ovale is apparent.

PMID- 9625341
TI  - Postnatal body weight curves for infants below 1000 g birth weight receiving
      early enteral and parenteral nutrition.
AB  - No body weight curves are available for preterm infants < 1000 g birth weight
      receiving early enteral and parenteral nutrition. Postnatal weight changes of 136
      infants with a birth weight < 1000 g were analysed retrospectively. Body weight
      curves for the first 30 days of life were generated for five separate birth
      weight groups (430-599 g, 600-699 g, 700-799 g, 800-899 g, 900-999 g). All
      infants had received intravenous glucose and amino acids from day 1 and
      intravenous lipids from day 2. Enteral feeding was started on day 1. Thus caloric
      intake (+/-SD) was advanced to 384+/-46 kJ/kg per day (92+/-11 kcal/kg/day) in
      the 1st week of life. In 136 preterm infants mean postnatal weight loss was
      10.1%+/-4.6% of birth weight, birth weight was regained at a mean postnatal age
      of 11+/-3.7 days, but significantly earlier (7.8+/-3.5 days) in the lowest
      compared to the highest weight group. Mean subsequent weight gain was 15.7+/-7.2
      g/ kg per day. This was accomplished by exclusive enteral nutrition from day 20
      (median). CONCLUSION: Our body weight curves are more adequate to evaluate growth
      of preterm infants than older published reference values because they are based
      on infants treated according to current nutritional standards.

PMID- 9625342
TI  - Primary ciliary dyskinesia: evolution of pulmonary function.
AB  - Pulmonary function tests were obtained in 11 patients with primary ciliary
      dyskinesia. Their mean age was 15 years (range 6-32). Their pulmonary function
      was obstructive, with a vital capacity (mean+/-SD) of 75%+/-20% predicted, a
      forced expiratory volume in 1s (FEV1) of 63%+/-20% predicted and a raised
      residual volume of 169%+/-50% predicted. After inhalation of 200 microg of
      salbutamol the mean change in FEV1 was + 13.2%+/-9.6% of the baseline value. In
      the 10 oldest patients, lung function had been measured at regular intervals
      during 3 20 years. Interestingly, during childhood and adolescence the evolution
      was not unfavourable: vital capacity increased by 8%+/-20% and FEV1 remained
      stable (mean change 0.3%+/-12%). Only 2 patients had an unfavourable evolution.
      CONCLUSION: At time of diagnosis, patients with primary ciliary dyskinesia have
      partially reversible obstructive airway disease. During regular follow up and
      therapy, there is no evidence of a further decline in lung function. Patients
      with associated immunodeficiency or important damage at the start of therapy may
      have a worse prognosis.

PMID- 9625343
TI  - Pulmonary evolution of cystic fibrosis patients colonized by Pseudomonas
      aeruginosa and/or Burkholderia cepacia.
AB  - We analysed the pulmonary evolution (radiological scores and pulmonary function)
      of 81 cystic fibrosis (CF) patients colonized by Pseudomonas aeruginosa (PA), by
      Burkholderia cepacia (BC) or by both these bacteria, compared to a control group.
      Pulmonary function was compared in the age bracket 6-13 years. Functional vital
      capacity (FVC) and forced expiratory volume (FEV1) values for PA colonized
      patients were significantly worse than for the control group but better than for
      children colonized by both organisms. In this last group, the evolution of
      radiological scores and pulmonary function showed a greater decline 2 years after
      the first colonization compared to the other groups. FVC and FEV1 values in
      patients colonized by BC were not worse than these of patients colonized by PA.
      Moreover, BC affected older patients with advanced lung disease and often
      previously colonized with PA. These results suggested that co-colonization by PA
      and BC could be a more deleterious factor on the pulmonary evolution than the
      isolated colonization by PA or BC, and that BC could be a severity marker rather
      than a cause. In addition, after starting the utilization of mouthpieces with
      filter at single use for spirometry in 1993 (without any other change in
      preventive measures already taken during hospitalization), incidence of BC
      decreased from 8.2% to zero, and no new case of BC colonization has been observed
      over the last 4 years. CONCLUSION: Co-colonization of CF patients by PA and BC is
      more deleterious for pulmonary evolution than colonization by one of these
      bacteria alone. Re-inforcement of environmental measures during hospitalization
      (e.g. use of disposable mouthpieces for spirometry) was sufficient to reduce the
      transmission of BC.

PMID- 9625344
TI  - Social class and obesity in 12-year-old children in Brussels: influence of gender
      and ethnic origin.
AB  - From their school health files, the body mass index of 2607 children, 1268 boys
      and 1339 girls, from the Brussels region of Belgium was analysed. The aim was to
      study the relationship between obesity and social class, gender and nationality.
      In Belgian girls, the lower their social class, the higher was the prevalence and
      severity of obesity. There was no such significant relationship in Belgian boys,
      nor in immigrant children of either sex, although the overall prevalence of
      obesity was similar in all groups. These results question certain hypotheses
      proposed to explain the relationship between social class and obesity.
      CONCLUSION: From early adolescence on, social inequality influences the
      prevalence of obesity in Belgian girls, but not in Belgian boys nor in immigrant
      children. Prevention of obesity should take into account the influence of gender,
      social class and ethnic origin.

PMID- 9625345
TI  - Early nasal CPAP reduces the need for intubation in VLBW infants.

PMID- 9625347
TI  - Mechanical ventilation in bone marrow transplanted children; do they benefit?

PMID- 9625346
TI  - Neonatal morbidity and mortality associated with maternal haemolysis, elevated
      liver enzymes and low platelets syndrome--the impact of neutropenia.

PMID- 9625348
TI  - Magnetic resonance imaging for early detection of bronchial foreign bodies.

PMID- 9625350
TI  - Transient neutropenia may be a risk of treating preterm neonates with high doses
      of recombinant erythropoietin.

PMID- 9625349
TI  - Steroid-resistant inflammatory bowel disease: a patient with non-compliance in
      the hospital.

PMID- 9625351
TI  - Partial co-existence of NADPH-diaphorase and acetylcholinesterase in the
      hypothalamic magnocellular secretory nuclei of the rat.
AB  - Co-localization of NADPH-diaphorase (ND) and acetylcholinesterase (AChE)
      activities were explored in the magnocellular secretory nuclei of the rat
      hypothalamus by means of a double histochemical staining of the same sections.
      Partial co-existence was found in all the nuclei studied (paraventricular,
      supraoptic, fornicals and circular nuclei). No particular location of the neurons
      expressing both markers was found, although in the paraventricular nucleus all of
      them (ND +, AChE + and neurons expressing both markers) were preferentially
      located in the magnocellular subdivisions whereas in the parvicellular ones only
      some neurons belonging to all three types were detected, mainly located in the
      periventricular and medial subdivisions. The lowest degree of co-existence was
      found at the level of the main magnocellular nuclei (supraoptic and
      paraventricular) when compared with the accessory magnocellular nuclei,
      especially the posterior fornical and the circular nuclei. These results extend
      previous data on the chemical nature of the neurons producing nitric oxide in the
      neurosecretory nuclei and the possible functional role of this atypical messenger
      in the hypothalamus.

PMID- 9625352
TI  - Functional AMPA/kainate receptors in human embryonic and foetal central nervous
      system.
AB  - Here, functional AMPA/kainate receptors in human embryonic (5.5-7.5 gestational
      weeks) and foetal (8-10 gestational weeks) central nervous system tissue, shown
      by the cobalt labeling method, are reported. Specific agonist-induced cobalt
      incorporation was detected in brainstem and spinal cord cells, even in the
      youngest embryo studied. T-AMPA or kainate, but also vegetal toxins such as L
      BOAA or acromelate, induced accumulation of cobalt. In contrast, no labeling was
      observed after exposure to KCl or NMDA. Cobalt labeled cells were particularly
      prominent in motor regions of brainstem and spinal cord. Co-application of the
      diuretic agent cyclothiazide, a desensitization blocker at AMPA receptors,
      dramatically increased the number of stained cells, which was particularly
      obvious in sensory regions, suggesting different receptor properties in motor
      versus sensory regions. This is the first study providing evidence for functional
      AMPA/kainate receptors, permeable to divalent cations, in brainstem and spinal
      cord at an early stage of human central nervous system development. Since many
      developmental processes are influenced by the modulation of cytosolic calcium,
      exposure at critical stages of embryogenesis to food or drug substances modifying
      the activity of AMPA/kainate receptors may alter brain development.

PMID- 9625353
TI  - Tyrosine hydroxylase- and/or aromatic L-amino acid decarboxylase-containing cells
      in the suprachiasmatic nucleus of the Syrian hamster (Mesocricetus auratus).
AB  - Catecholamines, including dopamine (DA), affect the activity of cells in the
      suprachiasmatic nucleus (SCN) of the hypothalamus, the principal circadian clock
      in mammals. This study examined the distribution of dopaminergic cells in the SCN
      of the male Syrian hamster, using both single- and double-label
      immunocytochemistry for tyrosine hydroxylase (TH), the rate-limiting enzyme in DA
      synthesis and for aromatic L-amino acid decarboxylase (AADC), the second enzyme
      needed to produce DA. Some neurons immunopositive for TH (TH + ) were found in
      the SCN, but most of the TH + cells of the region were located just outside the
      borders of the nucleus, as defined by pyronin Y staining. In the SCN, 91% of
      these cells were also immunopositive for AADC and thus, likely to be
      dopaminergic. Cells positive for AADC, many of which were not TH +, were found
      throughout the SCN, with the highest concentration seen in the ventral aspects of
      the nucleus. Cells containing AADC, but lacking TH may synthesize products other
      than DA, such as trace amines. These anatomical observations suggest that local
      neurons that produce DA and perhaps trace amines, may play a role in SCN function
      and in the neural control of circadian rhythms.

PMID- 9625354
TI  - Separate populations of neurons within the paraventricular hypothalamic nucleus
      of the rat project to vagal and thoracic autonomic preganglionic levels and
      express c-Fos protein induced by lithium chloride.
AB  - The role of different hypothalamic nuclei, particularly the paraventricular
      nucleus (PVN), in the control of food intake and feeding behaviour is well known.
      It is also well established that lithium chloride (LiCl) causes various disorders
      in feeding behaviour. In this study, we analyzed the precise distribution of
      hypothalamic neurons activated by i.p. LiCl administration (LCA neurons) and
      compared it to that of hypothalamic neurons which project to autonomic
      preganglionic levels (HAP neurons). We also analysed the possibility that some
      neurons belong to both populations of nerve cells. To this end, a multiple
      labelling technique, using two retrograde fluorescent tracers together with c-Fos
      like immunohistochemistry, was performed. Fast Blue was injected in the dorsal
      motor nucleus of the vagus and Fluorogold (FG) in the thoracic intermedial
      lateral cell column, to trace parasympathetic and sympathetic pathways,
      respectively. LiCl was used as stimulus for c-Fos-like immunohistochemistry. HAP
      neurons were located mainly in the dorsal, ventral and lateral regions of the
      parvocellular PVN, while LCA neurons were observed predominantly in the
      magnocellular region of the PVN rostrally to HAP neurons. A significant number of
      FG/Fos double-labelled neurons were located in the dorsal parvocellular
      subnucleus of the PVN (dp) in the LiCl-stimulated rats. We concluded that there
      is a clear segregation of LCA neurons from HAP neurons within the PVN. The
      presence of FG/Fos double-labelled neurons in the dp suggests that this nucleus
      could mediate a sympathetic response after LiCl administration.

PMID- 9625355
TI  - Distribution and effects of testosterone on aromatase mRNA in the quail
      forebrain: a non-radioactive in situ hybridization study.
AB  - A number of studies have been devoted to the analysis of the anatomical
      distribution, control by steroids and functional significance of aromatase (the
      enzyme metabolizing testosterone into 17beta-estradiol) in the quail brain. In
      particular, the sexually dimorphic nucleus preopticus medialis has been the main
      focus of investigation because testosterone aromatization in this structure
      mediates the activation of male sexual behavior and aromatase activity is itself
      testosterone-dependent in this nucleus. No information on the anatomical
      distribution of aromatase gene expression is, however, available so far in this
      avian species. In the present study we applied a non-radioactive in situ
      hybridization technique to describe the distribution of aromatase mRNA containing
      neurons in the quail prosencephalon. We also analyzed, at a neuronal level of
      resolution, the induction by testosterone of this mRNA in the medial preoptic
      nucleus. Dense clusters of aromatase gene expressing neurons were observed within
      the medial preoptic nucleus, the nucleus of the stria terminalis, the ventro
      medial hypothalamus and the tuberal region. Scattered neurons expressing lower
      levels of aromatase mRNA were also found in the dorsal thalamic area and central
      gray. The specificity of the staining was confirmed by demonstrating the absence
      of signal in sections that had been hybridized with a sense probe. Moreover, the
      distribution of the aromatase mRNA containing cells completely overlapped with
      the distribution of the aromatase-immunoreactive cells. Aromatase-mRNA expression
      was controlled by testosterone (or its metabolites) in the entire medial preoptic
      nucleus. Castration resulted in a decrease in the number of aromatase mRNA
      containing cells and this effect was totally reversed by testosterone treatment.
      These data further support the idea that testosterone regulates the rate of its
      own aromatization by modulating the expression of aromatase rather than by acting
      at a post transcriptional level.

PMID- 9625356
TI  - Mutations of follicle-stimulating hormone and its receptor: effects on gonadal
      function.
AB  - The physiological functions of the two gonadotropins, follicle-stimulating
      hormone (FSH) and luteinizing hormone (LH), are quite well known in both males
      and females. Nevertheless, the recent unraveling of structures of the
      gonadotropin and gonadotropin receptor genes has provided us with tools to obtain
      completely new information on the functions of these hormones at the molecular
      level. Several gain- and loss-of-function mutations of these genes have been
      discovered in humans, and the first knock-out experiments with these genes in the
      mouse have been recently published. The purpose of the present review is to
      describe the current state of knowledge on human mutations of FSH and its
      receptor, as well as on relevant animal models.

PMID- 9625357
TI  - Hormonal control of programmed cell death/apoptosis.
AB  - Apoptosis or programmed cell death is a physiological form of cell death that
      occurs in embryonic development and during involution of organs. It is
      characterized by distinct biochemical and morphological changes such as DNA
      fragmentation, plasma membrane blebbing and cell volume shrinkage. Many hormones,
      cytokines and growth factors are known to act as general and/or tissue-specific
      survival factors preventing the onset of apoptosis. In addition, many hormones
      and growth factors are also capable of inducing or facilitating programmed cell
      death under physiological or pathological conditions, or both. Steroid hormones
      are potent regulators of apoptosis in steroid-dependent cell types and tissues
      such as the mammary gland, the prostate, the ovary and the testis. Growth factors
      such as epidermal growth factor, nerve growth factor, platelet-derived growth
      factor (PDGF) and insulin-like growth factor-I act as survival factors and
      inhibit apoptosis in a number of cell types such as haematopoietic cells,
      preovulatory follicles, the mammary gland, phaeochromocytoma cells and neurones.
      Conversely, apoptosis modulates the functioning and the functional integrity of
      many endocrine glands and of many cells that are capable of synthesizing and
      secreting hormones. In addition, exaggeration of the primarily natural process of
      apoptosis has a key role in the pathogenesis of diseases involving endocrine
      tissues. Most importantly, in autoimmune diseases such as autoimmune thyroid
      disease and type 1 diabetes mellitus, new data suggest that the immune system
      itself may not carry the final act of organ injury: rather, the target cells
      (i.e. thyrocytes and beta cells of the islets) commit suicide through apoptosis.
      The understanding of how hormones influence programmed cell death and,
      conversely, of how apoptosis affects endocrine glands, is central to further
      design strategies to prevent and treat diseases that affect endocrine tissues.
      This short review summarizes the available evidence showing where and how
      hormones control apoptosis and where and how programmed cell death exerts
      modulating effects upon hormonally active tissues.

PMID- 9625358
TI  - Fluor-18-deoxyglucose positron emission tomography in differentiated thyroid
      cancer.

PMID- 9625359
TI  - Oestrogens--essential for reproduction in males, too.

PMID- 9625360
TI  - Serum leptin levels in children and adolescents with insulin-dependent diabetes
      mellitus in relation to metabolic control and body mass index.
AB  - The ob protein, termed leptin, is produced by adipocytes and is thought to act as
      an afferent satiety signal regulating weight through suppressing appetite and
      stimulating energy expenditure in humans and/or rodents. Insulin has been found
      to be a potent stimulator of leptin expression in rodents. It is unclear at
      present whether this insulin action is a direct or an indirect effect. To
      investigate whether leptin concentrations in children and adolescents with type 1
      diabetes (IDDM) were related to metabolic status, body weight, body mass index
      and insulin treatment, we have measured leptin concentrations in serum from 13
      newly diagnosed IDDM patients before the beginning of insulin treatment (8 girls,
      5 boys, aged 4.7-17.5 years) and in 134 patients with IDDM during treatment (64
      girls, 70 boys, aged 2.6-20.1 years) using a specific radioimmunoassay. The data
      from patients with diabetes were compared with normative data that were derived
      from a large cohort of healthy children and adolescents. Serum from children with
      newly diagnosed diabetes had significantly lower levels of leptin (mean 1.28+/
      1.60 ng/ml, range 0.14-6.13 ng/ml) compared with healthy children (n=710) (mean
      2.2 ng/ml, range 0.26-14.4ng/ml) and compared with insulin-treated children and
      adolescents (mean 5.18+/-5.48 ng/ml, range 0.26-29.77 ng/ml) (P<0.0001) even
      after adjustment for gender and body mass index (BMI). Serum leptin levels in
      patients with IDDM were significantly correlated with BMI (r=0.42, P<0.0001).
      Multiple regression analysis showed that age and BMI were significantly
      correlated with leptin levels, while duration of diabetes, mean HbA1c levels,
      insulin dose and plasma glucose, triglyceride and cholesterol levels were not.
      Females had higher serum leptin concentrations than males even when adjusted for
      BMI (P<0.0001). Surprisingly and most importantly, leptin levels in insulin
      treated young adult (Tanner stage 5) patients were significantly higher than
      values found in the healthy nondiabetic reference population when adjusted for
      sex, Tanner stage and BMI. These findings suggest that leptin levels in IDDM
      patients show a similar dependency on adipose tissue and age as in healthy,
      normal children. The data provide evidence that insulin may be of importance as a
      regulator of serum leptin levels in vivo not only in rodents but also in humans.
      It is hypothesized that the elevated BMI-adjusted leptin levels in adolescents
      with IDDM could indicate either that these patients may be oversubstituted by the
      intensified insulin therapy that they are receiving or that their body
      composition and body fat content may differ from that of healthy adolescents in
      the sense that they have a relative increase in fat mass.

PMID- 9625361
TI  - Effect of growth hormone treatment on insulin action in adipocytes from children
      with Prader-Willi syndrome.
AB  - OBJECTIVE: To study the effect of growth hormone (GH) treatment (2-4 months) on
      insulin action in adipocytes isolated from children with Prader-Willi syndrome
      (PWS), in whom GH deficiency appears to be a primary defect. We investigated the
      complex effects of GH on carbohydrate metabolism, as part of a current clinical
      trial of GH treatment in children with PWS. METHODS: Biopsies of subcutaneous
      abdominal adipose tissue were obtained from 12 children with PWS before and after
      2-4 months of GH treatment. Lipogenesis was determined by the incorporation of
      radiolabelled glucose into lipids in isolated adipocytes, and glycerol release to
      the incubation medium was used as an index of lipolysis. GLUT4 RNA was measured
      by solution hybridization. RESULTS: With low glucose concentrations, at which
      glucose transport is rate-limiting, maximal insulin-induced lipogenesis was
      increased by 120% after GH treatment (P < 0.05), but the sensitivity to insulin
      (half-maximum effective hormone concentration) was unchanged. This was not
      accompanied by a significant change in the RNA expression of GLUT4. Neither
      responsiveness (maximum effect) nor sensitivity of insulin-induced inhibition of
      lipolysis was affected by GH treatment. CONCLUSIONS: GH treatment of children
      with PWS results in an upregulation of insulin-induced lipogenesis in isolated
      adipocytes, with no effect on insulin-induced inhibition of lipolysis. The data
      suggest that the site of the effect of GH on lipogenesis is distal to the insulin
      hormone-receptor interaction, but does not involve altered GLUT4 expression.

PMID- 9625362
TI  - Relationship of chronic endurance exercise to the somatotropic and sex hormone
      status of older men.
AB  - To investigate putative abrogating effects of habitual endurance exercise on age
      related changes in endocrine function and body composition, we compared insulin
      like growth factor-I (IGF-I), sex hormonal status and body composition in 15
      Masters runners and 15 minimally exercising men (MEM) aged 60-70 years. A higher
      maximal oxygen uptake (VO2 max.) in the runners (41.4+/-1.6 compared with 27.3+/
      1.4 ml/kg/min, P=0.0001; mean+/-S.E.M.) reflected our group allocations. Analysis
      of body composition and bone mineral density (BMD) by dual energy X-ray
      absorptiometry showed no group differences in lean tissue mass or in regional or
      whole body BMD, but MEM were heavier, reflecting greater adiposity. Of nine
      muscle groups tested, only quadriceps strength differed significantly, being
      greater in runners (60.3+/-2.8 compared with 51.1+/-2.3 kg, P=0.02). Total IGF-I
      (129+/-10 compared with 124+/-11 ng/ml, P=0.72) and IGF-binding protein-3 (2854+/
      94 compared with 2623+/-128ng/ml, P=0.16), were similarly depressed compared with
      young adult norms in both groups. There was no relationship between total or
      bioavailable IGF-I and any body composition, BMD or muscle strength variable. In
      the runners, concentrations of total testosterone (19.1+/-0.8 compared with
      15.0+/-0.9 nmol/l, P=0.002) and sex hormone binding globulin (SHBG) (124.4+/-21.6
      compared with 67.7+/-11.6 nmol/l, P=0.03) were significantly greater, but the
      free androgen index was significantly lower (20.7+/-2.7 compared with 31.4+/-4.1,
      P=0.04). Directly measured free testosterone, however, was similar between the
      runners and MEM (47.9+/-1.8 compared with 47.1+/-2.0 nmol/l P=0.80). Therefore
      the group differences in total testosterone and free androgen index were due to
      their different SHBG concentrations. Although estrone concentration was higher in
      MEM (85.1+/-5.2 compared with 108+/-6.7 pmol/l, P=0.03), estradiol concentration
      was similar between groups (73.0+/-6.3 compared with 81.8+/-8.0 pmol/l, P=0.18),
      indicating that estrogens were not responsible for the increased SHBG in runners.
      These results indicate that even high levels of regular endurance exercise do not
      prevent the decline in the somatotropic axis that occurs with aging. Furthermore,
      the somatic effects of exercise in older men (reduced adiposity and increased
      regional muscle strength) occurred independently of somatotropic or androgen
      status. Although habitual exercise does not influence free testosterone
      concentrations in older men, it appears to enhance the age-associated increase in
      SHBG synthesis.

PMID- 9625363
TI  - IGF-I and IGF-binding protein-1 are related to cortisol in human cord blood.
AB  - OBJECTIVE: To assess cortisol concentrations in cord blood and investigate their
      relationships with the IGF system. STUDY DESIGN: Fifteen newborns with birth
      weight appropriate for gestational age (AGA) and 30 children with intrauterine
      growth retardation (IUGR) were studied. Serum samples were collected from
      umbilical cord blood and cortisol, IGF-I and IGF-binding proteins (IGFBPs)-1 and 
      3 were measured. IUGR infants were followed up for 3 months with repeated
      measurements of weight, supine length and knee-heel length (by knemometry).
      RESULTS: IUGR newborns showed significantly greater concentrations of IGFBP-1
      (P<0.0001) and lower concentrations of IGF-I (P< 0.0001) and IGFBP-3 (P< 0.0001)
      than did controls. In AGA children, cortisol correlated inversely with IGF-I (r=
      0.75, P< 0.002) and directly with IGFBP-1 (r=0.52, P <0.05), whereas no
      correlation between cortisol and IGF system-related variables was observed in
      IUGR. Finally, in IUGR children an inverse correlation was found between length
      gain in the first trimester of life and cortisol concentrations at birth (r=
      0.54, P < 0.005). CONCLUSIONS: Cortisol might be a physiological regulator of
      fetal growth, at least in the last part of pregnancy, by modulating IGF-I and
      IGFBP-1 release under conditions of fetal stress. In IUGR children, a
      rearrangement of this growth control mechanism seems to occur. The close inverse
      relationship of cortisol with linear growth, if confirmed by large-scale studies,
      suggests cord blood cortisol to be potentially predictive of early postnatal
      catch-up growth in IUGR infants.

PMID- 9625365
TI  - Thyroid size and thyroid function during pregnancy: an analysis.
AB  - An analysis of all available studies of thyroid size and function in pregnancy
      reveals that thyroid size, estimated by inspection and palpation or measured more
      accurately by ultrasonography, increases in pregnancy in areas of iodine
      deficiency but not in those with sufficient iodine. The increase in average
      thyroid size is within the normal range, and can partly be prevented by treatment
      with extra iodine or thyroxine. There is a slight transient increase in free
      thyroxine in the first trimester, probably as a result of physiological
      stimulation of thyroid function by human choriogonadotrophin. These levels then
      decrease by about 30% to low normal values in the second and third trimesters of
      pregnancy in both iodine-depleted and -replete areas. These changes resemble
      those of non-thyroidal illness and may well play a role in reducing energy
      expenditure during pregnancy. The increase in thyroid size in iodine-deficient
      areas is probably due to autoregulatory mechanisms of iodine on thyroid growth.
      The hypothesis is supported by the fact that, during pregnancy, thyroid volume
      and thyroid function adapt in a physiological way to meet the increased demands
      for iodine and energy.

PMID- 9625364
TI  - Calcitonin levels are similar in goitrous euthyroid patients with or without
      thyroid antibodies, as well as in hypothyroid patients.
AB  - OBJECTIVE: Some authors, after studying retrospectively immunostained sections of
      thyroid specimens, found C-cell hyperplasia (CCH) unrelated to medullary thyroid
      carcinoma to be frequent in thyroid glands affected by chronic lymphocytic
      thyroiditis (CLT); others failed to observe this association. The purpose of the
      present study was to further investigate prospectively the existence of the
      proposed relationship between CLT and CCH by measuring circulating calcitonin
      (CT) levels. DESIGN: Basal serum CT was measured in 174 euthyroid goitrous women
      with negative thyroid autoantibodies (TA-Neg) and 124 age-matched goitrous
      euthyroid women with positive antibodies (TA-Pos). A calcium-infusion test was
      performed in 27 TA-Neg and 31 TA-Pos age-matched euthyroid goitrous women. Basal
      CT was also determined in 51 hypothyroid women and 40 control normal healthy
      women. METHODS: Serum CT was measured using a specific and sensitive two-site
      immunoassay which detects mainly the CT-32 monomer. Thyroid autoantibodies (anti
      thyroid peroxidase and anti-thyroglobulin) were measured in serum by quantitative
      RIAs. RESULTS: Basal serum CT was found to be similar in TA-Neg and TA-Pos
      euthyroid as well as hypothyroid and normal control groups. A test of
      independence performed on the frequency distribution of the patients among
      sequential classes of serum CT showed that basal CT levels are independent of the
      presence of thyroid autoantibodies or hypothyroidism. Calcium-stimulated CT as
      well as the increase in CT were similar in TA-Neg and TA-Pos euthyroid goitrous
      women. There was no correlation between thyrotropin and CT in the hypothyroid
      group. CONCLUSION: Positive thyroid antibodies in goitrous patients do not
      predispose to hypercalcitoninemia. Elevated CT found in a patient with goitre and
      positive thyroid antibodies should not be ascribed to the underlying thyroiditis;
      this patient should be investigated for some other cause of the high CT.

PMID- 9625366
TI  - The effect of surgical treatment on secondary hyperaldosteronism and relative
      hyperinsulinemia in primary hyperparathyroidism.
AB  - OBJECTIVE: To evaluate the renin-aldosterone system and insulin secretion in
      hyperparathyroidism and their effects on blood pressure regulation. DESIGN:
      Studies were carried out on patients with primary hyperparathyroidism (PHPT)
      prior to and following removal of the parathyroid tumor. METHODS: Sixteen
      normotensive and euglycemic patients with PHPT were studied. The following
      parameters were measured: basal and stimulated plasma renin activity (PRA) and
      aldosterone (ALD) secretion: parathormone (PTH) and serum electrolytes. Insulin
      and glucose levels were measured during an oral glucose tolerance test. RESULTS:
      Systolic but not diastolic blood pressure showed a decrease following surgery,
      from 123.3+/-13.0/80+/-8.6 to 116.7+/-13.5/77.3+/-8.8 mmHg. The decrease in the
      systolic pressure was not clinically significant. After surgery, both the basal
      and stimulated PRA and ALD values decreased, and the preoperative pathological
      values returned to normal: PRA basal: 1.79 --> 0.70 ng/ml/h, P=0.0049; PRA
      stimulated: 7.76 --> 1.90 ng/ml/h, P=0.0031; ALD basal: 111.5 --> 73.0 pg/ml,
      P=0.0258; ALD stimulated: 392.5 --> 236.0 pg/ml, P=0.0157. The postoperative
      decrease in the PRA correlated with the changes in PTH levels (r=0.5442, P <
      0.05, n=16) but did not correlate with the changes in serum calcium
      concentrations. Both the fasting and stimulated insulin levels decreased after
      surgery but remained within the normal range: insulin fasting: 10.2 --> 5.0
      mIU/l, P=0.0218; insulin area under the curve: 5555 --> 3296 mIU/l*min, P=0.0218.
      There was no correlation between the changes in insulin levels and PTH or ion
      levels. Sodium, potassium and blood glucose levels remained unaffected by
      parathyroid surgery. CONCLUSIONS: In a population of normotensive
      hyperparathyroid patients an increased activity of the renin-aldosterone system
      related to PTH was found and surgery resulted in a small and insignificant
      decrease in blood pressure. This change was accompanied by a significant decrease
      in the activity of the renin-aldosterone system indicating the role of the renin
      aldosterone system in the regulation of blood pressure in PHPT. Both fasting and
      stimulated insulin values decreased following removal of the parathyroid tumor,
      but with no individual correlation with PTH and calcium levels.

PMID- 9625367
TI  - Laparoscopic adrenalectomy: a report on 50 operations.
AB  - OBJECTIVE: To investigate the feasibility, safety and results of laparoscopic
      transperitoneal adrenalectomies performed with the patient supine, in patients
      affected by secreting and silent adrenal lesions. METHODS: Exclusion criteria
      were suspected adrenal primary malignancies. Fifty patients (33 women and 17 men;
      mean age 49.6 years, range 19-75 years) underwent 51 laparoscopic adrenalectomies
      (one bilateral). After complete endocrinological evaluation, computed tomography
      or magnetic resonance imaging, or a combination thereof, 14 non-secreting
      adenomas, 13 aldosterone-producing adenomas, 13 cortisol-producing adenomas,
      eight phaeochromocytomas (one bilateral), one androgen-secreting adenoma, and two
      metastases were considered eligible for adrenalectomy. In five patients,
      associated procedures were performed during surgery. RESULTS: The lesions ranged
      in size from 1.5 to 10 cm. There were no intraoperative complications and no
      blood transfusions were required. The postoperative course was uneventful and
      painless in all patients. Mean postoperative hospital stay was 2.5 days. In all
      hypertensive patients, significant improvement or cure of hypertension was
      observed at follow-up (mean 18 months). In patients with secreting adenomas,
      normalization of hormone concentrations was obtained after removal of the tumour.
      In six patients with incidentaloma, the exaggerated 17-hydroxyprogesterone
      response to ACTH disappeared after surgery. CONCLUSIONS: Secreting and non
      secreting adrenal lesions were treated safely by laparoscopy. Relatively small
      incidentalomas and subclinical hormonally active tumours can be removed by
      laparoscopy. Early diagnosis enhances prevention and treatment.

PMID- 9625368
TI  - Primary ovarian failure caused by a solvent containing 2-bromopropane.
AB  - Sixteen Korean female laborers who had been exposed to a cleaning solvent
      composed mainly of 2-bromopropane developed primary ovarian failure. Histologic
      findings from these patients' ovaries were similar to those observed in ovarian
      failure caused by radiation or chemotherapy, i.e., reduced number and
      developmental arrest of primary follicles, interstitial fibrosis and
      hyalinization of blood vessels. We followed their clinical course for 2 years and
      found that two patients recovered normal ovarian function spontaneously: one
      became pregnant and delivered a normal full-term baby, and the other resumed
      regular menstrual periods with normal hormonal values. Our observations support
      the idea that the increasing prevalence of ovarian failure in recent years might
      be due to an increase in presently unidentified environmental toxic agents.

PMID- 9625369
TI  - Familial isolated hyperparathyroidism due to multiple adenomas associated with
      ossifying jaw fibroma and multiple uterine adenomyomatous polyps.
AB  - We describe three siblings with hyperparathyroidism due to multiple parathyroid
      adenomas without evidence of other endocrinological abnormalities. A 22-year-old
      woman had two parathyroid adenomas complicated by multiple ossifying jaw
      fibromas. Her sister, aged 29, also suffered from primary hyperparathyroidism
      associated with two parathyroid adenomas one of which was also suspected to be a
      carcinoma. These two female patients had unusual multiple small uterine polyps,
      which were diagnosed as adenomyomatous polyps. Their brother, aged 17, had two
      parathyroid adenomas complicated by urolithiasis. These three patients are
      characterized by young adult-onset familial isolated hyperparathyroidism due to
      multiple adenomas with various complications including ossifying jaw fibroma and
      uterine adenomyomatous polyps. These clinical features are different from those
      of familial hyperparathyroidism associated with multiple endocrine neoplasia.

PMID- 9625370
TI  - Transient cold nodule of the thyroid due to localized postpartum thyroiditis.
AB  - A 27-year-old woman with no previous personal or family history of thyroid
      disease was referred to us for the evaluation of thyroid nodule, five months
      postpartum. Thyroid scintigraphy demonstrated a left cold nodule. Fine needle
      aspiration cytology of the nodule showed a mixture of colloid, follicular cells
      and lymphocytes, suggesting lymphocytic thyroiditis. Thyroid function tests were
      normal and thyroid autoantibodies were negative. After two months the thyroid
      nodule was not palpated and thyroid scintigraphy returned to normal. Thyroid
      function tests remained normal twelve months after delivery. These findings
      suggest that postpartum thyroiditis may present as a localized transient form and
      should be considered in the differential diagnosis of painless solitary nodule
      that appears postpartum.

PMID- 9625371
TI  - Intra-adrenal factors are not involved in the differential control of cortisol
      and adrenal androgens in human adrenals.
AB  - The differential control of adrenal androgens and cortisol may be due to intra
      adrenal factors, which may be age- or sex-related, or due to extra-adrenal
      factors, such as circulating hormones. The purpose of this study was to identify
      any intrinsic differences that may exist in steroidogenic production occurring
      within adrenals obtained from males and females, and any maturational differences
      that may evolve with age. Using human adrenals from 48 transplant donors (32
      males, 16 females; ages 5-60 years), the influences of age and sex on basal
      production of and ACTH-stimulated cortisol, androstenedione and
      dehydroepiandrosterone (DHEA) were examined in freshly prepared adrenal cell
      suspensions. Basal and ACTH-stimulated cortisol, androstenedione and DHEA
      production were similar in adrenals from males and females and did not correlate
      significantly with age when the whole group was examined. When steroidogenesis in
      male and female adrenals was examined separately against age, a significant
      correlation was observed only for basal and ACTH-stimulated androstenedione in
      adrenals from males in the younger age group, 5-30 years (basal: r=0.84,
      P=0.0001; ACTH-stimulated: r=0.52, P=0.007). Examination of the relationships
      between the steroids disclosed that the basal and ACTH-stimulated
      cortisol/androgen ratios did not correlate significantly with age, but the
      androstenedione/DHEA ratio showed a significant direct relationship with age in
      males only (basal: r=0.53, P=0.006; ACTH-stimulated: r=0.5, P=0.01). These data
      suggest that the influences of sex and age are minor in the modulation of adrenal
      steroidogenesis and support the concept that extra-adrenal factors dominate in
      the differential modulation of adrenal androgens and cortisol. The relationship
      between the androstenedione/ DHEA ratio and increasing age in men is consistent
      with the recently reported stimulatory effect of testosterone on adrenal
      steroidogenesis by induction of the conversion of DHEA to androstenedione.

PMID- 9625372
TI  - Effect of medroxyprogesterone acetate on sex hormone-binding globulin mRNA
      expression in the human endometrial cancer cell line Ishikawa.
AB  - To understand the rationale of high-dose medroxyprogesterone acetate (MPA) in the
      treatment of well-differentiated uterine endometrial cancers, the effect of MPA
      on intracellular sex hormone-binding globulin (SHBG) mRNA expression in well
      differentiated uterine endometrial cancer cell line Ishikawa was determined by
      competitive reverse transcription-polymerase chain reaction-Southern blot
      analysis. Estradiol-17beta (E2, 10(-8) mol/l) did not alter SHBG mRNA expression,
      but the addition of 10(-10) mol/l MPA increased it, while a high concentration of
      MPA (10(-6) to 10(-5) mol/l) with or without E2 suppressed it. Furthermore. a
      high dose (10(-6) mol/l) of chlormadinone acetate or danazol with or without E2
      significantly suppressed its expression, while MPA was the most effective among
      the hormones tested. The effect of MPA and the other steroid hormone analogs on
      SHBG expression was not mediated via the progesterone receptor. These findings
      suggest that intracellular SHBG suppression might partly contribute to the
      abolition of the intracellular estrogen-dominant milieu, and may be involved as
      one of the mechanisms of the antitumoral effects of high-dose MPA on the
      development and growth of some well-differentiated endometrial cancer cells.

PMID- 9625373
TI  - Alpha- but not beta-adrenergic receptors mediate the effect of angiotensin II in
      the medial preoptic area on gonadotropin and prolactin secretion.
AB  - The aim of this work was to study the participation of alpha- and beta-adrenergic
      receptors on the effect of microinjection of angiotensin II (A II) into the
      medial preoptic area (MPOA) on the secretion of luteinizing hormone (LH),
      follicle-stimulating hormone (FSH) and prolactin (PRL) in estrogen-primed
      ovariectomized (OVX) rats. Microinjection of A II into the MPOA increased plasma
      LH. This effect was reduced by previous microinjection of an alpha-
      (phentolamine), but not a beta- (propranolol) adrenergic blocker into the MPOA.
      Plasma PRL decreased after microinjection of A II into the MPOA, but this effect
      was unchanged by phentolamine or propranolol. There was no change in plasma FSH
      in any condition. These results indicate that A II in the MPOA stimulates LH
      secretion and inhibits PRL secretion in estrogen-primed OVX rats. The effect on
      secretion of LH, but not of PRL, is mediated by alpha-adrenergic receptors in the
      MPOA.

PMID- 9625374
TI  - Effect of dehydroepiandrosterone sulfate on interleukin-8 receptor during
      cervical ripening.
AB  - We investigated the effects of dehydroepiandrosterone sulfate (DHA-S) on the
      production of interleukin-8 (IL-8) and expression of the interleukin-8 receptor
      (IL-8 R) in human cervical tissue. DHA-S increased the levels of IL-8 in cultured
      human cervical fibroblasts and in the supernatant in a time- and dose-dependent
      manner. DHA-S induced IL-8 and IL-8 R expression in human cervical fibroblasts
      and human pregnant cervical tissue at term in a dose-dependent manner. In
      addition, it induced the expression of IL-8 R in an explant culture of human
      cervical tissue and cultured human cervical fibroblasts in a time- and dose
      dependent manner. However, dehydroepiandrosterone (DHA) only slightly induced the
      production of IL-8 and the expression of IL-8 R in the same cells and tissue.
      These results suggest that DHA-S up-regulates the autocrine system of IL-8
      through the expression of IL-8 R.

PMID- 9625375
TI  - The role of tyrosine kinase in gonadotropin-induced ovulation in the rat ovary.
AB  - OBJECTIVES: Our purpose was to elucidate the involvement of the tyrosine kinase
      pathway in gonadotropin-induced ovulation in the rat ovary. STUDY DESIGN: We
      investigated the effect of a tyrosine kinase inhibitor, tyrphostin, on the rat
      ovulatory process in vivo and in vitro. METHODS: In cultured rat granulosa cells,
      the effect of tyrphostin on LH-, dibutyryl cyclic AMP ((Bu)2cAMP)- or forskolin
      stimulated tissue type plasminogen activator (tPA) activities was examined by
      using a fibrin autography technique. In an in vivo system, tyrphostin was
      injected into the bursal cavity of the ovary in pregnant mare serum gonadotropin
      treated rats, just before human chorionic gonadotropin administration. After 24
      h, the number of oocytes in the oviduct was counted and the tyrphostin-treated
      ovaries were examined histologically. RESULTS: Tyrphostin inhibited LH-stimulated
      tPA activity but did not affect (Bu)2cAMP- or forskolin-stimulated ones. In an in
      vivo study, tyrphostin suppressed oocyte release dose-dependently. Histological
      observations revealed that tyrphostin-treated ovaries contained many large
      unruptured follicles and a few corpora lutea. CONCLUSION: This study suggests
      that the suppressive effect of tyrphostin on ovulation may be partly due to tPA
      activity inhibition in the granulosa cells via the suppression of tyrosine kinase
      activity. Additionally, tyrosine kinase phosphorylation may be involved in
      gonadotropin-activated signaling systems in the rat ovulatory process.

PMID- 9625376
TI  - Cancer and acquired immunodeficiency syndrome wasting syndromes: current and
      future therapies.

PMID- 9625377
TI  - Normal digestive physiology and the evaluation of digestive function.
AB  - Normal digestion is a complex and coordinated process that breaks food into
      constitutive molecules, some of which are absorbed and others passed through the
      body as waste. Many of the conditions associated with wasting syndromes alter
      normal digestive function and can lead to or exacerbate malnutrition. Digestive
      function can be defined by applying the principles of normal physiology. Our
      laboratory has developed a relatively comprehensive stable isotope method to
      assess function, which shows promise as a screening tool in evaluating patients
      with wasting syndromes. This and other tests of digestive function can be used to
      define the abnormalities associated with wasting and to direct or optimize
      antiwasting therapy.

PMID- 9625378
TI  - The role of body composition measurements in wasting syndromes.
AB  - Wasting is a state of nonvolitional weight loss that frequently afflicts patients
      with cancer or those infected with the human immunodeficiency virus. Body
      composition measurements afford a more clinically relevant assessment of an
      individual's functional capacity, energy stores, and prognosis. Several
      techniques of body composition measurements exist, each with selected advantages
      and disadvantages. This review summarizes the methods and the utility of body
      composition analysis.

PMID- 9625379
TI  - Integrating proactive nutritional assessment in clinical practices to prevent
      complications and cost.
AB  - Timely and appropriate nutritional interventions for patients with cancer and/or
      human immunodeficiency virus (HIV) infection require adoption of routine
      nutritional screening and comprehensive evaluations into clinical practice.
      Traditionally, the clinical skills necessary for comprehensive nutritional
      evaluation have not been a part of medical education. Likewise, the importance of
      nutritional screening and assessment has not been fully appreciated. In the
      context of current health care, these skills are increasingly important in
      maintaining or improving patient care and improving clinical and economic
      outcomes. It is imperative that nutritional screening be routinely implemented in
      all clinical settings (eg, office practices, clinics, preadmission units,
      homecare) to offset the impact of decreased rates of hospital admission.
      Hospitals have traditionally been the setting for dietetic screening and
      intervention and nutritional support services. Therapy for patients with cancer
      or HIV infection is increasingly being managed primarily or entirely in an
      outpatient setting. When nutritional risk or deficit is identified on screening,
      it is important to carry out sequential reassessment after intervention. This
      article reviews the principles of nutritional screening and comprehensive
      assessment. It includes a detailed overview of an instrument that can be used for
      either nutritional screening or assessment in patients with either malignancy or
      HIV infection.

PMID- 9625380
TI  - Recently identified peptides involved in the regulation of body weight.
AB  - The application of molecular and genetic techniques to the study of body weight
      regulation have produced exciting new insights into the physiological systems
      governing energy expenditure, appetite, and metabolic signaling. A number of new
      peptides have been identified that play important roles in these regulatory
      systems. These include the hormone leptin, the short and long forms of the leptin
      receptor, uncoupling proteins, agouti protein, melanocortin receptor isoforms,
      melanin-concentrating hormone, and the proteins responsible for tub and fat, two
      monogenic mouse models of obesity. This article reviews some of the new insights
      gained from studies of these peptides. Although much of this new knowledge has
      come from studies of obesity, there may be implications for the clinical
      syndromes associated with weight loss. As more is learned about these systems,
      potential new targets for therapeutic intervention will likely become evident.
      These interventions may develop first as obesity treatments, but investigators
      and clinicians involved in the care of cachectic patients should follow these
      scientific developments as well.

PMID- 9625381
TI  - Approach to the seriously ill or terminal cancer patient who has a poor appetite.
AB  - Lack of appetite is a frequent complaint of patients with serious illness and is
      particularly bothersome to cancer patients and their families. As patients enter
      the terminal phase of their illness, poor appetite becomes an even more
      distressing problem that affects not only physical symptoms but also functional,
      social, and psychological aspects of a patient's quality of life. Family and
      friends frequently relate a patient's poor appetite as a specific contributor to
      their perception of lack of health. We have investigated a number of ways to
      approach the seriously ill or terminal cancer patient who has a poor appetite
      with education, dietary changes (including the use of smaller, more frequent
      meals but still providing the patient's favorite foods), and at times dietary
      supplements. Appetite stimulants such as Megace Oral Suspension (Bristol-Myers
      Squibb, Princeton, NJ) are used not so much for facilitating weight gain as for
      adding to the quality of life, including social and psychological well-being, by
      allowing patients to enjoy foods they like in a social family setting.

PMID- 9625382
TI  - Pharmacologic management of anorexia/cachexia.
AB  - Anorexia is a symptom seen in the majority of patients with cancer or the
      acquired immunodeficiency syndrome (AIDS) who experience involuntary weight loss.
      It is frequently not seen as a symptom requiring management in the same proactive
      manner as pain, nausea, or constipation. Progressive inanition or wasting is a
      fundamental component of the complex phenomenon known as the anorexia/cachexia
      syndrome (ACS) of malignancy or AIDS. Weight loss can be seen in the full
      spectrum of patient care settings: as a presenting complaint, defining condition,
      treatment-related toxicity, or as a hallmark of impending death. Primary
      pharmacologic management of ACS includes use of orexigenic agents (appetite
      stimulants), anticatabolic agents (antimetabolic and anticytokine), and anabolic
      agents (primarily hormonal). In addition to these specific categories of
      pharmacologic intervention, broad aspects of symptom management need to be
      addressed and are complementary. The available literature evaluating
      pharmacologic management of ACS in both malignancy and AIDS is reviewed.

PMID- 9625383
TI  - Cytokine activity in cancer-related anorexia/cachexia: role of megestrol acetate
      and medroxyprogesterone acetate.
AB  - The characteristic clinical picture of anorexia, tissue wasting, loss of body
      weight accompanied by a decrease in muscle mass and adipose tissue, and poor
      performance status that often precedes death has been named the cancer-related
      anorexia/cachexia syndrome (CACS). Chronic administration of pro-inflammatory
      cytokines, including interleukin-I (IL-I), IL-6, and tumor necrosis factor (TNF),
      either alone or in combination, is capable of reproducing the different features
      of CACS. High serum levels of these cytokines have been found in cancer patients,
      which seem to correlate with progression of the tumor. This article describes a
      series of experimental and clinical studies demonstrating that: (1) high serum
      levels of some cytokines, including IL-I, IL-6, and TNF, are present in advanced
      stage cancer patients, particularly those with CACS; (2) megestrol acetate (MA)
      has a beneficial therapeutic effect on CACS symptoms, such as appetite, body
      weight, and quality of life; (3) MA downregulates the synthesis and release of
      cytokines and relieves the symptoms of CACS; (4) cytokines play a key role in the
      onset of CACS; (5) medroxyprogesterone acetate (MPA) reduces the in vitro
      production of cytokines and serotonin (5-hydroxytryptamine, 5-HT) by peripheral
      blood mononuclear cells (PBMC) of cancer patients; and (6) MA and MPA reduce the
      cisplatin-induced 5-HT release in vitro from PBMC of cancer patients. Based on
      these results, a clinical study incorporating MA/MPA in combination with
      chemotherapy or chemoimmunotherapy may be warranted. In addition, it has been
      recently shown that "oxidative stress" resulting from reactive oxygen species,
      which can be induced by pro-inflammatory cytokines, is involved in tissue wasting
      and CACS. These results suggest promising approaches for the prevention and
      treatment of cytokine-induced CACS based on MA, MPA, and metabolic antioxidants.

PMID- 9625384
TI  - Anticytokine approaches to the treatment of anorexia and cachexia.
AB  - Proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) have a
      prominent role in the pathogenesis of anorexia and cachexia of chronic disease.
      Pentoxyfylline and thalidomide are inhibitors of TNF-alpha that have been tried
      as rational therapeutic interventions in cachexia. Preliminary studies with
      pentoxyfylline have not shown efficacy in reversing weight loss, despite evidence
      of TNF-alpha inhibition. In contrast, the administration of thalidomide to
      patients with human immunodeficiency virus- and/or tuberculosis-associated weight
      loss has consistently resulted in weight gain. However, the relationship of the
      metabolic benefits of thalidomide treatment to its complex effects on the immune
      system is imperfectly understood. Studies of thalidomide, either alone or in
      combination with other therapies for the treatment of cancer cachexia, are
      warranted.

PMID- 9625385
TI  - Megestrol acetate as a biomodulator.
AB  - Megestrol acetate is a synthetic analog of progesterone. In general, megestrol
      acetate exerts its progesterone-like hormonal effect by binding to the
      progesterone receptor. It has been recognized that megestrol acetate can increase
      weight and improve some aspects of quality of life in cancer patients and in
      patients with the acquired immunodeficiency syndrome. This effect occurs in
      patients with or without concurrent chemotherapy or radiotherapy, through an as
      yet unknown mechanism. Recently, megestrol acetate has been shown to reverse, at
      least partially, multidrug resistance to doxorubicin and/or vincristine in cancer
      cell lines. This potentially beneficial effect has not yet been studied in
      clinical trials. This biological activity is thought to be mediated through the
      unique binding of megestrol acetate to p-glycoprotein. At least in vitro
      megestrol acetate can also enhance the cytotoxic effect of these two
      chemotherapeutic agents in some MDR-nonexpressing cell lines. These findings
      suggest that megestrol acetate deserves further preclinical and clinical studies
      to evaluate its potential role of enhancing cytotoxicity of chemotherapy and
      improving the quality of life of cancer patients.

PMID- 9625386
TI  - Pharmacoeconomics of nutritional support in cancer.
AB  - Physicians are increasingly asked to consider the cost of interventions,
      including procedures and drugs, when making medical decisions. This article
      provides some practical information about the cost and efficacy of a variety of
      nutrition support measures for patients with cancer or acquired immunodeficiency
      syndrome-associated anorexia and undernutrition. Nutrition counseling, liquid
      homemade or commercially available food supplements, and appetite stimulants are
      relatively low-cost, effective means of nutrition support. Enteral nutrition
      requires invasive procedures, is more expensive, is associated with more
      potentially serious complications, and should be reserved for patients whose
      nutritional status cannot be maintained with less aggressive measures. Total
      parenteral nutrition is exceedingly expensive and seldom helpful; it should be
      reserved for those patients whose gastrointestinal tract is nonfunctional. In
      addition to nutritional parameters and cost, the clinician should consider
      patient preferences. Specific tools to assess the impact of nutrition support
      measures on patients' quality of life are under development.

PMID- 9625387
TI  - Human immunodeficiency virus-related wasting: malabsorption syndromes.
AB  - Diarrhea and malabsorption are common findings in patients with the acquired
      immunodeficiency syndrome (AIDS). The pathogenesis and consequences of
      malabsorption in human immunodeficiency virus (HIV) infection are similar to
      those found in non-HIV-related conditions, and are related to both direct
      intestinal damage and alterations in the coordination of the body's response to
      feeding. The pathogenesis of malabsorption is multifactorial and includes primary
      enterocyte injury with partial villus atrophy and crypt hyperplasia, ileal
      dysfunction with bile salt wasting and fat malabsorption, and exudative
      enteropathy. Clinical studies show that intestinal cryptosporidiosis leads to
      excess fecal losses of about 20% for protein and fat. The consequences of
      malabsorption include decreased appetite; "enterogastrone" effects including dry
      mouth, decreased gastric acid secretion, decreased rate of gastric emptying, and
      slowed intestinal transit; anemia resulting from iron, folate, or vitamin B12
      malabsorption; and metabolic effects including osteomalacia, gallstones, renal
      stones, and hypocholesterolemia. Few studies of nutritional therapy have been
      applied specifically to AIDS patients with malabsorption. Total parenteral
      nutrition promotes weight gain, although the response to this therapy depends on
      the underlying clinical problem, with body cell mass repletion noted in patients
      with malabsorption but predominantly fat gain in patients with systemic
      infections. Nutritional stabilization also was noted in response to oral
      administration of a semielemental diet.

PMID- 9625388
TI  - The etiology of wasting in the human immunodeficiency virus and acquired
      immunodeficiency syndrome.
AB  - Wasting is a debilitating complication of the human immunodeficiency
      virus/acquired immunodeficiency syndrome (HIV/AIDS) and is a major cause of
      morbidity and mortality. The etiology of wasting in HIV/AIDS is complex and its
      origins are multifactorial. Both patterns of simple starvation and the more
      complex metabolic and endocrine alterations associated with stress and trauma
      have been described in patients with the AIDS wasting syndrome. Observations
      suggest that the pathophysiology of the wasting in individual patients with
      HIV/AIDS may vary according to the primary cause of wasting and underlying
      disease activity. Optimal treatment of the AIDS wasting syndrome will depend on a
      thorough evaluation of all possible contributing factors. This review addresses
      the pathophysiologic basis of weight loss in HIV/AIDS, based on the current
      literature.

PMID- 9625389
TI  - Energy expenditure and protein metabolism in human immunodeficiency virus
      infection and cancer cachexia.
AB  - Malnutrition and weight loss are clinically significant complications of both
      human immunodeficiency virus (HIV) infection and cancer. Over the last two
      decades, multiple abnormalities in energy and protein metabolism have been
      documented in patients with cancer and, more recently, in HIV infection. In HIV
      infection, studies of the components of energy balance have demonstrated that
      weight loss results primarily from decreased energy intake, coupled with a
      failure to consistently reduce resting energy expenditure. Although several
      studies have shown that resting energy expenditure is elevated in many patients
      with HIV infection, other studies have shown that not all patients with HIV
      infection are hypermetabolic. Likewise, protein turnover is increased, decreased,
      or unchanged in patients with HIV infection and varies with the physiologic state
      of the patient. In cancer patients, studies of resting energy expenditure have
      produced similarly varying results, depending in part on tumor type and dietary
      intake. Protein turnover studies in patients with cancer suggest that support of
      the tumor may occur at the expense of host skeletal muscle. Abnormalities of
      glucose and lipid metabolism have been noted as well. Thus, pharmacologic
      intervention may be needed to restore weight and lean tissue in patients with
      weight loss associated with either HIV infection or cancer.

PMID- 9625390
TI  - Current antiretroviral therapy and its impact on human immunodeficiency virus
      related wasting.
AB  - Recent improvements in the management of people living with human
      immunodeficiency virus (HIV) disease in the United States have led to remarkable
      reductions in HIV-related morbidity and mortality. The Centers for Disease
      Control and Prevention recently reported substantial reductions in acquired
      immunodeficiency syndrome (AIDS)-related opportunistic infections and conditions,
      including HIV-related wasting. These achievements followed the introduction of
      the new class of antiretroviral therapies, the aspartyl protease inhibitors, and
      their use in combination with nucleoside inhibitors in so-called highly active
      antiretroviral therapies. In an effort to provide guidance for clinicians in HIV
      care, the Office of AIDS Research, United States Department of Health and Human
      Services recently convened a panel of experts to set clinical practice guidelines
      for the use of antiretroviral therapy in adults and adolescents. This article
      summarizes the new standard of care for the use of HIV therapies. It also reviews
      recent data suggesting that combination therapy has altered the natural history
      of HIV infection and has reduced the incidence of HIV-related nutritional
      disturbances and wasting.

PMID- 9625391
TI  - Single-agent/combination therapy of human immunodeficiency virus-related wasting.
AB  - Weight loss and wasting are significant contributors to morbidity in patients
      infected with the human immunodeficiency virus (HIV). The approach to the patient
      with HIV and weight loss needs to be proactive and comprehensive, as early
      intervention may be beneficial and the weight loss may be multifactorial.
      Evaluation for weight loss needs to be directed at any apparent contributing
      cause and can include dietary evaluation, treatment of intercurrent complicating
      infections or malignancies, and maximization of HIV therapy. Some patients will
      also benefit from an evaluation of the gastrointestinal tract to document
      malabsorption and/or opportunistic enteric infections. It is also prudent to
      evaluate testosterone levels in male patients. Interventions in the patient who
      is not able to take in sufficient calories should include dietary advice and/or
      nutritional supplements, as well as the use of appetite stimulants. Megace
      (Bristol-Myers Squibb, Princeton, NJ) has been shown to effectively increase
      appetite, oral intake, and body weight. For the patient with malabsorption and/or
      diarrhea, treatment of enteric infections should be attempted. These patients may
      benefit from the replacement of some dietary fat with medium-chain triglycerides,
      either in a nutritional product or to replace cooking oils. Other patients may
      benefit from the use of anabolic agents such as growth hormone, nandrolone,
      testosterone, or oxandrolone, which are all effective at increasing lean body
      mass. For select patients, agents such as thalidomide might be of benefit,
      although its mechanism of action is not clear. There are few data from
      prospective, controlled trials of combinations of these agents, but these studies
      are underway. It is likely that the optimal interventions for patients will be
      combinations of agents to improve oral intake and add lean body mass, which will
      permit a reduction in morbidity from weight loss and an improvement in quality of
      life for the HIV-infected patient.

PMID- 9625392
TI  - Clinical trials update in human immunodeficiency virus wasting.
AB  - The major acquired immunodeficiency syndrome (AIDS) clinical trials groups in the
      Division of AIDS of the National Institutes of Health have been investigating
      weight loss and wasting in persons with the human immunodeficiency virus (HIV)
      and AIDS. Both the AIDS Clinical Trials Group (ACTG) and the Terry Beirn
      Community Programs for Clinical Research on AIDS (CPCRA) have developed research
      projects to study the pathogenesis, diagnosis, prevention, and treatment of HIV
      related malnutrition and wasting. This article reviews multicenter trials
      concerning HIV-related malnutrition and wasting conducted by the AIDS clinical
      trials groups. CPCRA trials will examine the effects of caloric supplements and
      triglycerides, or the use of megestrol acetate, oxandrolone, and progressive
      resistance training, on weight loss in patients with HIV-associated wasting.
      Planned ACTG trials will study the effects of the combination of megestrol
      acetate and testosterone, the testosterone derivative nandrolone decanoate, or
      highly active antiretroviral therapy on weight loss. Results from these studies
      may also have relevance to clinical oncologists who are treating patients with
      cancer-related cachexia.

PMID- 9625393
TI  - Exercise and the treatment of wasting: aging and human immunodeficiency virus
      infection.
AB  - A common feature of human immunodeficiency virus (HIV) infection and aging is the
      loss of skeletal muscle mass. Although the causes of this loss of muscle are
      multifactorial, there may be some shared characteristics to this loss, and
      therefore common strategies for its prevention or reversal. For example, loss of
      muscle mass early in life and early in the progression of HIV infection may
      result from decreased levels of physical activity. The rapid loss of skeletal
      muscle mass at the end of life (sometimes referred to as failure to thrive
      syndrome) and in acquired immunodeficiency syndrome (AIDS) patients may also have
      common cause: cachexia. However, it also must be pointed out that loss of
      skeletal muscle mass with advancing age also may result from losses of motor
      units, decreased rate of skeletal muscle protein synthesis, and impaired
      regulation of appetite. These factors have not been demonstrated to be
      consequences of HIV infection. The use of exercise to treat the losses of muscle
      size, strength, and functional capacity holds great promise. Although the losses
      of muscle with HIV infection may be more rapid and dramatic than those seen with
      aging, resistance exercise training can attenuate or arrest this loss. In elderly
      people, resistance exercise has been demonstrated to result in increased nitrogen
      balance, muscle mass and strength, functional capacity, energy requirements, and
      when combined with a protein calorie supplement, increased energy intake. The use
      of resistance exercise in HIV-infected patients may also provide similar results.
      This review discusses many of the changes in body composition, physiological
      function, and metabolism associated with aging and HIV infection. The specific
      effects of exercise in the elderly and in patients infected with HIV on the
      treatment of muscle wasting, and its consequences are also discussed.

PMID- 9625394
TI  - Mediterranean diets and cancer prevention.

PMID- 9625395
TI  - Case of the month: Institutional autopsy rates. Autopsy Committee of the College
      of American Pathologists.

PMID- 9625396
TI  - The troponins.

PMID- 9625397
TI  - Mediterranean dietary pattern in a randomized trial: prolonged survival and
      possible reduced cancer rate.
AB  - BACKGROUND: The Mediterranean dietary pattern is thought to reduce the risk of
      cancer in addition to being cardioprotective. However, no trial has been
      conducted so far to prove this belief. METHODS: We compared overall survival and
      newly diagnosed cancer rate among 605 patients with coronary heart disease
      randomized in the Lyon Diet Heart Study and following either a cardioprotective
      Mediterranean-type diet or a control diet close to the step 1 American Heart
      Association prudent diet. RESULTS: During a follow-up of 4 years, there were a
      total of 38 deaths (24 in controls vs 14 in the experimental group), including 25
      cardiac deaths (19 vs 6) and 7 cancer deaths (4 vs 3), and 24 cancers (17 vs 7).
      Exclusion of early cancer diagnoses (within the first 24 months after entry into
      the trial) left a total of 14 cancers (12 vs 2). After adjustment for age, sex,
      smoking, leukocyte count, cholesterol level, and aspirin use, the reduction of
      risk in experimental subjects compared with control subjects was 56% (P=.03) for
      total deaths, 61% (P=.05) for cancers, and 56% (P=.01) for the combination of
      deaths and cancers. The intakes of fruits, vegetables, and cereals were
      significantly higher in experimental subjects, providing larger amounts of fiber
      and vitamin C (P<.05). The intakes of cholesterol and saturated and
      polyunsaturated fats were lower and those of oleic acid and omega-3 fatty acids
      were higher (P<.001) in experimental subjects. Plasma levels of vitamins C and E
      (P<.05) and omega-3 fatty acids (P<.001), measured 2 months after randomization,
      were higher and those of omega-6 fatty acids were lower (P<.001) in experimental
      subjects. CONCLUSIONS: This randomized trial suggests that patients following a
      cardioprotective Mediterranean diet have a prolonged survival and may also be
      protected against cancer. Further studies are warranted to confirm the data and
      to explore the role of the different lipids and fatty acids in this protection.

PMID- 9625398
TI  - Garlic powder and plasma lipids and lipoproteins: a multicenter, randomized,
      placebo-controlled trial.
AB  - BACKGROUND: Garlic powder tablets have been reported to lower serum cholesterol
      levels. There is widespread belief among the general public that garlic powder
      tablets aid in controlling cholesterol levels. However, much of the prior data
      demonstrating the cholesterol-lowering effect of garlic tablets involved studies
      that were inadequately controlled. OBJECTIVE: To determine the lipid-lowering
      effect of garlic powder tablets in patients with hypercholesterolemia. METHODS:
      This was a randomized, double-blind, placebo-controlled, 12-week, parallel
      treatment study carried out in 2 outpatient lipid clinics. Entry into the study
      after 8 weeks of diet stabilization required a mean low-density lipoprotein
      cholesterol level on 2 visits of 4.1 mmol/L (160 mg/dL) or lower and a
      triglyceride level of 4.0 mmol/L (350 mg/dL) or lower. The active treatment arm
      received tablets containing 300 mg of garlic powder (Kwai) 3 times per day, given
      with meals (total, 900 mg/d). This is equivalent to approximately 2.7 g or
      approximately 1 clove of fresh garlic per day. The placebo arm received an
      identical-looking tablet, also given 3 times per day with meals. The main outcome
      measures included levels of total cholesterol, triglycerides, low-density
      lipoprotein cholesterol, and high-density lipoprotein cholesterol after 12 weeks
      of treatment. RESULTS: Twenty-eight patients (43% male; mean +/- SD age, 58 +/-
      14 years) received garlic powder treatment and 22 (68% male; mean +/- SD age, 57
      +/- 13 years) received placebo treatment. There were no significant lipid or
      lipoprotein changes in either the placebo- or garlic-treated groups and no
      significant difference between changes in the placebo-treated group compared with
      changes in the garlic-treated patients. CONCLUSION: Garlic powder (900 mg/d)
      treatment for 12 weeks was ineffective in lowering cholesterol levels in patients
      with hypercholesterolemia.

PMID- 9625399
TI  - Prevention and Treatment of Hypertension Study (PATHS): effects of an alcohol
      treatment program on blood pressure.
AB  - OBJECTIVE: To determine whether blood pressure is reduced for at least 6 months
      with an intervention to lower alcohol intake in moderate to heavy drinkers with
      above optimal to slightly elevated diastolic blood pressure, and whether
      reduction of alcohol intake can be maintained for 2 years. DESIGN: A randomized
      controlled trial. METHODS: Six hundred forty-one outpatient veterans with an
      average intake of 3 or more alcoholic drinks per day in the 6 months before entry
      into the study and with diastolic blood pressure 80 to 99 mm Hg were randomly
      assigned to a cognitive-behavioral alcohol reduction intervention program or a
      control observation group for 15 to 24 months. The goal of the intervention was
      the lower of 2 or fewer drinks daily or a 50% reduction in intake. A subgroup
      with hypertension was defined as having a diastolic blood pressure of 90 to 99 mm
      Hg, or 80 to 99 mm Hg if recently taking medication for hypertension. RESULTS:
      Reduction in average weekly self-reported alcohol intake was significantly
      greater (P<.001) at every assessment from 3 to 24 months in the intervention
      group vs the control group: levels declined from 432 g/wk at baseline by 202 g/wk
      in the intervention group and from 445 g/wk by 78 g/wk in the control group in
      the first 6 months, with similar reductions after 24 months. The intervention
      group had a 1.2/0.7-mm Hg greater reduction in blood pressure than the control
      group (for each, P = .17 and P = .18) for the 6-month primary end point; for the
      hypertensive stratum the difference was 0.9/0.7 mm Hg (for each, P = .58 and P =
      .44). CONCLUSIONS: The 1.3 drinks per day average difference between changes in
      self-reported alcohol intake observed in this trial produced only small
      nonsignificant effects on blood pressure. The results from the Prevention and
      Treatment of Hypertension Study (PATHS) do not provide strong support for
      reducing alcohol consumption in nondependent moderate drinkers as a sole method
      for the prevention or treatment of hypertension.

PMID- 9625400
TI  - Montelukast, a once-daily leukotriene receptor antagonist, in the treatment of
      chronic asthma: a multicenter, randomized, double-blind trial. Montelukast
      Clinical Research Study Group.
AB  - OBJECTIVES: To determine the clinical effect of oral montelukast sodium, a
      leukotriene receptor antagonist, in asthmatic patients aged 15 years or more.
      DESIGN: Randomized, multicenter, double-blind, placebo-controlled, parallel-group
      study. A 2-week, single-blind, placebo run-in period was followed by a 12-week,
      double-blind treatment period (montelukast sodium, 10 mg, or matching placebo,
      once daily at bedtime) and a 3-week, double-blind, washout period.
      SETTING/PATIENTS: Fifty clinical centers randomly allocated 681 patients with
      chronic, stable asthma to receive placebo or montelukast after demonstrating a
      forced expiratory volume in 1 second 50% to 85% of the predicted value, at least
      a 15% improvement in forced expiratory volume in 1 second (absolute value) after
      inhaled beta-agonist administration, a minimal predefined level of daytime asthma
      symptoms, and inhaled beta-agonist use. Twenty-three percent of the patients used
      concomitant inhaled corticosteroids. PRIMARY END POINTS: Forced expiratory volume
      in 1 second and daytime asthma symptoms. RESULTS: Montelukast improved airway
      obstruction (forced expiratory volume in 1 second, morning and evening peak
      expiratory flow rate) and patient-reported end points (daytime asthma symptoms,
      "as-needed" beta-agonist use, nocturnal awakenings) (P<.001 compared with
      placebo). Montelukast provided near-maximal effect in these end points within the
      first day of treatment. Tolerance and rebound worsening of asthma did not occur.
      Montelukast improved outcome end points, including asthma exacerbations, asthma
      control days (P<.001 compared with placebo), and decreased peripheral blood
      eosinophil counts (P<.001 compared with placebo). The incidence of adverse events
      and discontinuations from therapy were similar in the montelukast and placebo
      groups. CONCLUSIONS: Montelukast, compared with placebo, significantly improved
      asthma control during a 12-week treatment period. Montelukast was generally well
      tolerated, with an adverse event profile comparable with that of placebo.

PMID- 9625401
TI  - From a prospective study of chronic cough: diagnostic and therapeutic aspects in
      older adults.
AB  - BACKGROUND: Cough is the most common complaint for which adults see a physician
      in the ambulatory setting in the United States. An anatomical diagnostic protocol
      has been used since 1981 to evaluate patients with chronic cough. It has been
      shown to be effective in diagnosing the cause of cough and leading to specific
      treatment in a variety of adult populations but has never been evaluated
      specifically in a population of older adults. OBJECTIVES: To question whether the
      spectrum and frequency of causes of chronic cough and the response to therapy
      would be different in older adults. METHODS: Thirty patients at least 64 years of
      age with a history of cough lasting at least 3 weeks were prospectively evaluated
      with a protocol designed to detect diseases that stimulate the afferent limb of
      the cough reflex. The final diagnosis of the cause of chronic cough required
      fulfillment of pretreatment criteria and having cough disappear with specific
      therapy. When more than one disease fulfilled pretreatment diagnostic criteria,
      therapy was instituted in the order that these were fulfilled. Probability
      statistics were used to describe the testing characteristics of individual
      components of the diagnostic protocol in terms of sensitivity, specificity,
      positive predictive value, and negative predictive value as they applied to
      chronic cough. RESULTS: Forty causes of chronic cough were identified in all 30
      patients. Postnasal drip syndrome, gastroesophageal reflux disease, and asthma
      were the most common causes of chronic cough, accounting for 85% of all causes
      found. Among patients with normal chest radiograph findings who were not
      cigarette smokers and not taking an angiotensin-converting enzyme inhibitor,
      postnasal drip syndrome, gastroesophageal reflux disease, and asthma accounted
      for 100% of all causes found. Specific therapy was successful in eliminating
      chronic cough in 100% of the patients studied. Except for barium esophagography,
      all laboratory tests for which information was available had sensitivities and
      negative predictive values of 100%. CONCLUSIONS: Postnasal drip syndrome,
      gastroesophageal reflux disease, and asthma accounted for 85% of all causes of
      chronic cough in older adults. Chronic cough caused substantial physical and
      emotional morbidity among older patients. The major value of performing objective
      testing in evaluating chronic cough is its ability to rule out specific diseases
      as a diagnostic possibility. The following clinical profile consistently predicts
      patients with cough attributable to gastroesophageal reflux disease: the patient
      has cough that has been persistently troublesome for at least 3 weeks; does not
      smoke cigarettes; does not take an angiotensin-converting enzyme inhibitor; does
      not have or has not responded to therapy for postnasal drip syndrome and asthma;
      and has normal or nearly normal findings and stable chest radiograph. The
      differences between what we observed regarding chronic cough in older adults and
      observations by ourselves and others regarding chronic cough in general are
      minor.

PMID- 9625402
TI  - Managed care and outcomes of hospitalization among elderly patients with
      congestive heart failure.
AB  - BACKGROUND: Little was known about the impact of the health maintenance
      organization-managed care on patients hospitalized for congestive heart failure.
      Understanding this issue is important with regards to the increasing prevalence
      of congestive heart failure among the elderly population as well as the growing
      enrollment of Medicare beneficiaries in managed care. OBJECTIVE: To examine the
      impact of the health maintenance organization-managed care on the outcomes of
      hospitalization among patients with congestive heart failure. PATIENTS AND
      METHODS: We analyzed the Oregon hospital discharge data set. Study subjects were
      all patients with congestive heart failure aged 65 years or older (N=5821)
      discharged from hospitals in 1995 and classified into 6 insurance groups: managed
      care, Medicare, Medicaid, commercial or private insurance, self-pay, and other.
      RESULTS: The percentage of patients admitted to hospitals via emergency
      departments was significantly higher in the managed care patients (69%) than in
      other health insurance coverage groups (29.0%-58.5%; P<.001). After adjusting for
      age, sex, and comorbidity, the managed care patients experienced a similar length
      of hospital stay (3.6 days) as the commercial or private insurance patients (3.7
      days; P = .67), but a shorter length of hospital stay than the Medicare patients
      (4.0 days; P<.001), self-pay patients (4.5 days; P<.001), and other patients (4.8
      days; P<.001). No difference in the in-hospital mortality rate was seen among the
      insurance groups (P = .37). The readmission rate was slightly higher in managed
      care patients (9.1%) than in commercial insurance patients (6.8%) and Medicare
      patients (7.5%). The differences, however, were not statistically significant
      after adjusting for the confounding factors (P = .59). CONCLUSIONS: Our results
      suggest no association between managed care and poor short-term outcomes of
      hospitalization in patients with congestive heart failure. Attention, however,
      needs to be paid to the increased use of emergency departments by managed care
      patients.

PMID- 9625403
TI  - Primary care practice adherence to National Cholesterol Education Program
      guidelines for patients with coronary heart disease.
AB  - BACKGROUND: Clinical trials demonstrate significant benefit from cholesterol
      management for patients with cardiovascular disease (CVD). National guidelines
      recommending goals for screening and treatment were published in 1993 and widely
      disseminated. This study examines cholesterol screening and management by primary
      care physicians after the guidelines were released. METHODS: Medical records and
      patient surveys provided data for 603 patients with CVD, aged 27 to 70 years,
      from 45 practices in 4 states during 1993 to 1995. Physician surveys measured
      estimated performance and other variables. Physician and patient factors
      associated with adherence, or lack of adherence, to national guidelines were
      examined using univariate and multivariate analyses. RESULTS: A total of 199
      patients (33%) with CVD were not screened with lipid panels, 271 patients (45%)
      were not receiving dietary counseling, and 404 (67%) were not receiving
      cholesterol medication. Only 84 patients (14%) with CVD had achieved the
      recommended low-density lipoprotein level of less than 2.58 mmol/L (100 mg/dL)
      and 302 (50%) had triglyceride levels lower than 2.26 mmol/L (200 mg/dL).
      Patients with a revascularization history and higher low-density lipoprotein
      and/or triglyceride levels were more likely to receive treatment, but other
      patient factors, including CVD risk factors, did not predict treatment. Physician
      specialty was not associated with differences in treatment, but physicians in
      practice for fewer years ordered more lipid panels. CONCLUSIONS: Most patients
      with CVD in primary care were not receiving cholesterol screening and management
      as recommended by the National Cholesterol Education Program guidelines in the 2
      years after their release. Increasing cholesterol screening and treatment should
      be a priority for practice quality improvement and could result in significant
      reductions in CVD events for high-risk patients.

PMID- 9625404
TI  - Cost-effectiveness of the arthritis self-help course.
AB  - OBJECTIVE: To evaluate the cost-effectiveness of the Arthritis Self-Help Course
      in reducing the pain of arthritis, the leading cause of disability in the United
      States and a common problem among older adults. METHODS: A decision model was
      used to examine the cost-effectiveness of the Arthritis Self-Help Course among
      individuals with arthritis over a 4-year analytic horizon from 2 perspectives,
      namely, society and the health care system. The Arthritis Self-Help Course was
      assumed to reduce pain by 20% and physician visits for arthritis by 40% among
      individuals receiving conventional medical therapy. Estimates for program costs,
      costs for physician visits, and time and transportation costs were derived from
      the published literature and expert opinion. Sensitivity analyses were conducted
      on all relevant parameters. Arthritis pain and costs (program, physician visit
      plus/minus time and transportation) were expressed as cost per person per unit
      reduction in pain. Because nearly all analyses showed the program to be cost
      saving, we simply report the reduction in joint pain and the cost savings,
      because standardizing cost savings is not a useful concept. RESULTS: From both
      the societal and health care system perspectives, the Arthritis Self-Help Course
      was cost saving in base-case analyses (reducing pain by 0.9 units while saving
      $320 and $267, respectively) and throughout the range of reasonable values used
      in univariate sensitivity analyses. Cost savings were due primarily to reduced
      physician visits. CONCLUSIONS: The Arthritis Self-Help Course is a cost-saving
      intervention that further reduces arthritis pain among individuals receiving
      conventional medical therapy. The benefits for both patients and health care
      providers warrant its more widespread use as a normal adjunct to conventional
      therapy.

PMID- 9625405
TI  - Effective lipid modification by partial ileal bypass reduced long-term coronary
      heart disease mortality and morbidity: five-year posttrial follow-up report from
      the POSCH. Program on the Surgical Control of the Hyperlipidemias.
AB  - BACKGROUND: In 1990, when the Program on the Surgical Control of the
      Hyperlipidemias (POSCH) reported its in-trial results strongly supporting the
      conclusion that effective lipid modification reduces progression of
      atherosclerosis, the differences for the end points of overall mortality and
      mortality from atherosclerotic coronary heart disease (ACHD) did not reach
      statistical significance. METHODS: The Program on the Surgical Control of the
      Hyperlipidemias recruited men and women with a single documented myocardial
      infarction between the ages of 30 and 64 years who had a plasma cholesterol level
      higher than 5.69 mmol/L (220 mg/dL) or higher than 5.17 mmol/L (200 mg/dL) if the
      low-density lipoprotein cholesterol level was in excess of 3.62 mmol/L (140
      mg/dL). Between 1975 and 1983, 838 patients were randomized: 417 to the diet
      control group and 421 to the diet plus partial ileal bypass intervention group.
      Mean patient follow-up for this 5-year posttrial report was 14.7 years (range,
      12.2-20 years). RESULTS: At 5 years after the trial, statistical significance was
      obtained for differences in overall mortality (P = .049) and mortality from ACHD
      (P = .03). Other POSCH end points included overall mortality (left ventricular
      ejection fraction > or =50%) (P = .01), mortality from ACHD (left ventricular
      ejection fraction > or =50%) (P = .05), mortality from ACHD and confirmed
      nonfatal myocardial infarction (P<.001), confirmed nonfatal myocardial infarction
      (P<.001), mortality from ACHD, confirmed and suspected myocardial infarction and
      unstable angina (P<.001), incidence of coronary artery bypass grafting or
      percutaneous transluminal coronary angioplasty (P<.001), and onset of clinical
      peripheral vascular disease (P = .02). There were no statistically significant
      differences between groups for cerebrovascular events, mortality from non-ACHD,
      and cancer. All POSCH patients have been available for follow-up. CONCLUSION: At
      5 years after the trial, all POSCH mortality and atherosclerosis end points,
      including overall mortality and mortality from ACHD, demonstrated statistically
      significant differences between the study groups.

PMID- 9625406
TI  - Retinal cholesterol emboli in the diagnosis of renal atheroembolism.
AB  - Three patients with renal failure caused by atheroembolism following cardiac
      vascular procedures had multiple, bilateral retinal cholesterol emboli.
      Ophthalmoscopy in such patients represents a noninvasive diagnostic technique
      that is underutilized.

PMID- 9625407
TI  - Actinomyces and the intrauterine device.

PMID- 9625408
TI  - The importance of initial heparin treatment on long-term clinical outcomes.

PMID- 9625409
TI  - The Joint National Committee on Prevention, Detection, Evaluation, and Treatment
      of High Blood Pressure and Obstructive Sleep Apnea: let their silence not be
      matched by the silence of the ordinary physician.

PMID- 9625410
TI  - Activated partial thromboplastin time vs heparin concentration.

PMID- 9625411
TI  - Pulmonary arterial carcinomatosis vs pulmonary embolism.

PMID- 9625412
TI  - HIV-infected pregnant women and progression of HIV disease.

PMID- 9625413
TI  - The "phen-pro" diet drug combination is not associated with valvular heart
      disease.

PMID- 9625414
TI  - Detection of apoptosis using hematoxylin-eosin.

PMID- 9625415
TI  - Application of synoptic reports.

PMID- 9625416
TI  - Interinstitutional comparison of bedside blood glucose monitoring program
      characteristics, accuracy performance, and quality control documentation: a
      College of American Pathologists Q-Probes study of bedside blood glucose
      monitoring performed in 226 small hospitals.
AB  - OBJECTIVES: To assess the accuracy of bedside blood glucose monitoring (BGM) in
      small hospitals, to assess the compliance with which hospital workers performing
      bedside BGM adhere to quality control (QC) procedures, and to identify those
      practice characteristics in small hospitals that are associated with better BGM
      accuracy and with better performance of BGM QC. DESIGN: Over a 1-month period in
      1996, voluntary participants in the College of American Pathologists Q-Probes
      laboratory quality improvement program prospectively compared glucose results of
      30 split samples run on BGM instruments with those performed on laboratory
      glucose analyzers, collected quality control data on up to five inpatient BGM
      instruments, and completed questionnaires profiling BGM practice characteristics
      in their institutions. SETTING AND PARTICIPANTS: Two hundred twenty-six hospitals
      with 200 or fewer occupied beds. MAIN OUTCOME MEASURES: The percentages of
      glucose determinations performed on BGM instruments differing by more than 10%,
      15%, and 20% from those split-sample results performed on laboratory glucose
      analyzers; the percent of BGM QC determinations required by institutions' BGM QC
      programs that BGM operators actually performed; and the percent of patient values
      reported when BGM QC was documented to be out of range and uncorrected, or
      reported when BGM QC was not performed at all. RESULTS: Of 6095 split-specimen
      glucose results that participants simultaneously performed on BGM instruments and
      on laboratory glucose analyzers, 45.6% differed from each other by more than 10%,
      approximately 25% differed from each other by more than 15%, and almost 14%
      differed from each other by more than 20%. Of 216 laboratories that performed at
      least 30 QC events during the study period, slightly over a third completed 100%
      of their required QC determinations, and 10% completed, at most, 77% of their
      required BGM QC determinations. Of 115,973 BGM determinations that participants
      reported on hospitalized patients, 3.3% were reported when QC was either out of
      range or when there was no documentation that QC had been performed at all.
      Better accuracy and/or better QC performance was associated with laboratory
      personnel rather than nursing personnel both supervising institutions' BGM QC
      programs and running institutions' daily routine BGM QC; with BGM operators both
      routinely running three, rather than two, levels of QC analytes; with BGM
      operators regularly comparing BGM results with laboratory analyzer glucose
      results; and with institutions participating in external proficiency programs.
      Institutions that completed all required BGM QC tasks tended to perform better on
      the BGM accuracy study than did those institutions that completed, at most, 77%
      of their required QC. CONCLUSIONS: We found the rates of BGM accuracy and of QC
      performance adequacy achieved in small hospitals to be similar to those
      determined in previous Q-Probes studies conducted in large institutions. A
      significant amount of institutional bedside testing does not meet current
      standards for accuracy or for quality control. Some institutions may improve
      their accuracy and/or QC performances by having laboratory personnel intimately
      involved in their institution's BGM QC program, by routinely comparing BGM
      results with those performed using glucose analyzers in the clinical laboratory,
      by routinely running three rather than two glucose QC control levels, by
      participating in external proficiency programs, and by strictly adhering to
      institutional QC protocols.

PMID- 9625417
TI  - A system to monitor a portion of the total testing process in medical clinics and
      laboratories: feasibility of a split-specimen design.
AB  - OBJECTIVE: The purpose of this study was to assess the feasibility of using a
      prototype split-specimen design to assess integrity of a portion of the total
      testing process in medical clinics and laboratories. DESIGN: Two or three tubes
      of venous blood were collected from 177 patients for analysis of one of three
      analytes (serum potassium, serum total cholesterol, and whole-blood hemoglobin).
      Patients were seen at one of the nine clinics participating in this study. In all
      cases, one tube of blood from each patient was sent to a commercial referral
      laboratory, and the other tube(s) forwarded to the laboratory that routinely
      tested specimens for the clinic (participating laboratory) for analysis. Each
      participating laboratory removed a preanalysis and sometimes a post-analysis
      aliquot from each specimen and forwarded these to the referral laboratory for
      analysis. SETTING: The study was conducted in six physician office laboratories
      (three serving 1 to 4 [mean, 2.7] internists and three serving 3 to 24 [mean, 12]
      family physicians) and three hospital laboratories (serving hospitals with 100 to
      more than 700 beds). PATIENTS: Study patients were voluntary participants and
      provided informed consent. Patient age ranged from 18 to 80 years, and for all
      the laboratory test was specifically ordered for clinical reasons. Patients who
      were unable or unwilling to provide informed consent, those for whom testing
      would require that they provide more than 100 mL of blood, those whose blood was
      being collected by fingerstick, and those with results that were part of a
      laboratory test profile were excluded. MAIN OUTCOME MEASURES: Two main outcome
      measures were assessed: (1) percent differences between split-specimen results
      exceeding the maximum allowable imprecision level, which was based on published
      biological variation data (defined as one-half of the intraindividual percent
      coefficient of variation), for each analyte (result discrepancies); and (2) all
      "problems" (defined as departures from standard operating procedures) that could
      be documented by retrospective review of all relevant medical and laboratory
      records. RESULTS: The rate of result discrepancies was 1 in 20 (5%) for patients
      in whom hemoglobin was analyzed, 12 in 57 (21%) for patients in whom potassium
      was analyzed, and 1 in 60 (2%) for patients in whom total cholesterol was
      analyzed. Results of samples obtained during the aliquoting and storage phases of
      the total testing process were subject to study-induced problems and were
      generally not useful in tracing problems to specific stages of the testing
      process. A total of 28 problems (involving 26 patients) were documented, but only
      6 problems were due to routine testing processes. CONCLUSIONS: The feasibility
      and limitations of a split-specimen design to detect result discrepancies were
      demonstrated. Most documented problems (22 of 28, or 79%) were study induced. To
      assess integrity of the total testing process, such problems need to be avoided.

PMID- 9625418
TI  - Assessment of the impact of a CD4+ T-cell testing laboratory improvement program.
AB  - OBJECTIVE: To evaluate the effectiveness of the Centers for Disease Control and
      Prevention's CD4+ T-cell laboratory testing improvement program and the influence
      of other laboratory improvement programs on CD4+ T-cell testing practices.
      DESIGN: Surveys asking for practice changes and factors that influenced the
      changes, a survey of clinicians' perceptions of laboratory quality in CD4
      testing, and analysis of data from the Model Performance Evaluation Program.
      INTERVENTIONS: Centers for Disease Control and Prevention interventions included
      a series of 3-day workshops on flow cytometry, CD4+ T-cell testing guidelines
      published in the Morbidity and Mortality Weekly Report, the Clinical Laboratory
      Improvement Amendments of 1988, and the Model Performance Evaluation Program.
      PARTICIPANTS: All known laboratories in the United States that perform clinical
      CD4+ T-cell testing, workshop participants, and a sample of clinicians that treat
      patients infected with the human immunodeficiency virus. MAIN OUTCOME MEASURES:
      Changes in practices, factors most influential in effecting change, and
      performance on samples mailed to laboratories by the Model Performance Evaluation
      Program; knowledge before and after presentation of material in workshops; and
      practicing clinicians' observations of any effects of changes in laboratory
      practices. RESULTS: Many existing laboratories changed practices as a result of
      both governmental and nongovernmental CD4+ T-cell testing improvement programs.
      Sources of influence varied with each testing practice. Perceptions that test
      results were more reproducible seemed to offset presumed increases in the time
      and cost of testing. Clinicians who had ordered CD4+ T-cell testing for more than
      10 years noted some improvements in results reported. CONCLUSIONS: As new complex
      testing methodologies are introduced into clinical and public health
      laboratories, the users seem to seek guidance in appropriate application of
      preanalytic, analytic, and postanalytic phases of the testing process. Testing
      improvement programs from a variety of sources were credited with changing
      practices and should continue to provide this guidance.

PMID- 9625419
TI  - Isolation of Inoue-Melnick virus from cerebrospinal fluid of patients with
      epidemic neuropathy in Cuba.
AB  - BACKGROUND: A mysterious disease spread over Cuba from 1991 to 1993, the cause of
      which has not been fully established. Major symptoms were the same in patients
      with the Cuban disease as in patients with subacute myelo-optico-neuropathy
      (SMON), which had occurred in Japan nearly 30 years ago and from which Inoue
      Melnick virus (IMV) type 1 was first isolated. We investigated the presence of
      IMV in cerebrospinal fluid samples of patients with this epidemic neuropathy in
      Cuba. METHODS: The established method for detecting IMV in MRC-5 fibroblasts was
      used throughout the study, which was conducted in two independent laboratories,
      one in Buffalo, NY, and the other in Kyoto, Japan. The cerebrospinal fluid
      samples of 20 patients and four controls were provided by Cuban researchers.
      RESULTS: All cerebrospinal fluid specimens from 20 Cuban patients tested were
      positive for IMV type 2 (100%), and four cerebrospinal fluid specimens from Cuban
      controls were negative for IMV (0%). These clear-cut results were identical in
      both laboratories. CONCLUSION: Our study indicates an important association of
      IMV type 2 with patients of this Cuban epidemic. The etiologic role of IMV type 2
      in the epidemic neuropathy in Cuba, along with weak cytopathic effect viruses
      isolated by the Cuban group, remains to be elucidated.

PMID- 9625420
TI  - Human immunodeficiency virus-2 infection in baboons is an animal model for human
      immunodeficiency virus pathogenesis in humans.
AB  - OBJECTIVE: To assess disease progression in baboons (Papio cynocephalus) that
      were infected with two human immunodeficiency virus-2 (HIV-2) isolates. METHODS:
      Eight baboons were inoculated intravenously with either HIV-2UC2 or HIV-2UC14 and
      were followed for a 2- to 7-year period of observation. RESULTS: Six of 8 baboons
      showed lymphadenopathy and other signs of HIV-related disease, 3 of 8 baboons had
      an acute phase CD4+ T-cell decline, and 2 of 5 baboons infected with the HIV-2UC2
      isolate progressed to an acquired immunodeficiency syndrome-like disease. Human
      immunodeficiency virus-2-specific pathology in lymphatic tissues included
      follicular lysis, vascular proliferation, and lymphoid depletion. Both
      neutralizing antibodies and a CD8+ T-cell antiviral response were associated with
      resistance to disease. CONCLUSIONS: Disease progression and the development of
      acquired immunodeficiency syndrome in HIV-2-infected baboons have similarities to
      human HIV infections.

PMID- 9625421
TI  - Confocal microscopy assessment of lymphoid tissues with follicular hyperplasia
      from patients infected with human immunodeficiency virus type 1.
AB  - OBJECTIVE: To characterize human immunodeficiency virus (HIV) infection of
      lymphoid tissues during follicular hyperplasia. METHODS: We examined 10
      tonsil/adenoid, 3 parotid lymphoepithelial cyst, and 7 lymph node specimens that
      had been surgically removed from 13 patients infected with HIV-1. Characteristics
      of productive HIV-1 infection were assessed using immunocytochemistry for HIV-1
      p24. Cellular colocalization was determined with the aid of a confocal microscope
      using double immunofluorescent staining for HIV-1 p24 and cell-specific markers.
      RESULTS: All specimens showed follicular hyperplasia. Using confocal microscopy
      with three-dimensional reconstruction, HIV-1 p24 was seen to be "intimately"
      colocalized with CD21 within the germinal centers. While lymphoid follicles were
      generally hyperplastic, only a subset of these follicles contained HIV-1 p24.
      Occasional HIV-1-expressing mononuclear cells identified outside follicles
      stained for CD68 or CD3. CONCLUSIONS: The differential involvement of
      hyperplastic follicles by HIV-1 within individual lymphoid tissues and the
      intimate colocalization of HIV-1 p24 and CD21 suggest that infected follicular
      dendritic cells may be an important reservoir of HIV-1 during follicular
      hyperplasia.

PMID- 9625422
TI  - CD10 expression in follicular lymphoma and large cell lymphoma is different from
      that of reactive lymph node follicles.
AB  - BACKGROUND AND OBJECTIVES: CD10 is a proteolytic enzyme expressed on the surface
      of germinal center cells and lymphomas derived from these cells. There is a well
      known association between CD10 expression and lymphomas of follicular center cell
      origin. However, the reported frequency of CD10 positivity in follicular
      lymphomas is widely variable, and no studies have addressed the importance of
      assessing the intensity of CD10 expression in the diagnosis of these tumors. In
      this study, we utilized flow cytometry to determine differences in CD10
      expression in lymphomas and follicular hyperplasias. METHODS: Cell suspensions
      from 61 follicular lymphomas, 43 diffuse large B-cell lymphomas, and 44 lymph
      nodes with follicular hyperplasia were analyzed simultaneously with phycoerythrin
      labeled anti-CD20 and fluorescein isothiocyanate-labeled anti-CD10. RESULTS: CD10
      expression was mainly observed on B cells and was detected in 89% of follicular
      lymphomas, 56% of diffuse large B-cell lymphomas, and 55% of lymph nodes showing
      follicular hyperplasia. In follicular hyperplasia, two subpopulations of B cells
      displaying dim and bright CD20 expression were recognized. CD10 expression was
      restricted to the bright CD20-positive cells, which accounted for an average of
      16% of B cells. In CD10-positive follicular and diffuse large B-cell lymphoma
      cases, a significantly higher proportion of B cells (73%) coexpressed CD10.
      Furthermore, the intensity of CD10 expression in follicular lymphoma and diffuse
      large B-cell lymphoma was much higher than that of follicular hyperplasia.
      CONCLUSIONS: Quantitative flow cytometry can detect significant differences in
      CD10 expression between normal follicular cells and follicular or diffuse large B
      cell lymphoma. The use of CD10 intensity of expression as well as the fraction of
      CD10-expressing B cells should help distinguish reactive from neoplastic B-cell
      processes.

PMID- 9625423
TI  - Mediastinal granulocytic sarcoma: a report of two cases.
AB  - We describe the cases of two patients who presented with granulocytic sarcoma
      with mediastinal involvement 15 and 21 months before development of acute myeloid
      leukemia. In both cases several bone marrow aspirates and trephine biopsy
      specimens, obtained at presentation and subsequently, revealed no evidence of
      leukemic infiltration. One case was originally misdiagnosed as large-cell non
      Hodgkin's lymphoma, which resulted in inappropriate therapy. In both cases
      immunohistochemical staining revealed that tumor cells were positive for
      leucocyte common antigen but not for conventional B- or T-lymphoid-cell markers.
      Retrospective analysis revealed that tumor cells in both cases were positive for
      myeloid markers. Histopathologists should be aware that granulocytic sarcoma may
      occur in unusual extramedullary sites without evidence of bone marrow
      involvement. If inappropriate treatment is to be avoided, a diagnosis of
      granulocytic sarcoma should be considered when hemopoietic tumor cells do not
      stain with conventional antibodies against B- and T-lymphoid cells. Both
      histochemical and immunohistochemical staining should be performed in such cases
      to determine whether the cells are of myeloid lineage. A diagnosis of
      granulocytic sarcoma is not ruled out when bone marrow biopsy specimens show no
      evidence of leukemic infiltration.

PMID- 9625424
TI  - Double heterozygosity for mutations in the BRCA1 and BRCA2 genes in a breast
      cancer patient.
AB  - BACKGROUND: Germline mutations in the tumor suppressor genes BRCA1 and BRCA2
      confer substantial increased lifetime risk for breast cancer, and in the case of
      BRCA1, for ovarian carcinoma as well. These two genes alone account for the vast
      majority of hereditary breast cancer families. Numerous mutations have been
      described in each gene, the majority of which are small insertions or deletions
      resulting in expression of a truncated protein. MATERIALS AND METHODS: Several
      common mutations can be detected using a polymerase chain reaction-mediated, site
      directed mutagenesis assay, which transforms the amplicon derived from either the
      wild-type or mutant allele by adding or removing a restriction endonuclease site.
      We screened 49 putative sporadic breast tumors using this methodology, targeting
      four BRCA1 mutations (185delAG, 5382insC, R1443X, and E1250X) and a single BRCA2
      mutation (6174delT). RESULTS: Using the polymerase chain reaction-mediated, site
      directed mutagenesis assay, we identified two mutations, namely, a 185delAG
      mutation (BRCA1) and a 6174delT mutation (BRCA2). Interestingly, these two
      mutations were found in the same sample. None of the remaining 48 breast tumors
      showed evidence of these mutations. Allele-specific oligonucleotide probes were
      then employed in conjunction with the Universal GeneComb Test Kit, which
      confirmed the presence of mutations. CONCLUSIONS: Our data suggest that the
      common germline BRCA1 and BRCA2 mutations are infrequently encountered in
      sporadic breast cancers. The one case with dual BRCA1 and BRCA2 mutations
      suggests that this tumor may be hereditary in origin, despite the lack of a
      positive family history. Double heterozygosity for mutations in BRCA1 and BRCA2
      may have increasingly significant implications with regard to predisposition to
      breast cancer.

PMID- 9625425
TI  - Expression spectrum of melanoma antigen-encoding gene family members in
      colorectal carcinoma.
AB  - OBJECTIVE: The 12 members of the human melanoma antigen-encoding (MAGE) gene
      family encode tumor-specific peptide antigens. Some antigens coded by the MAGE
      genes are potentially useful for cancer-specific immunotherapy. However, little
      information on the expression of these genes in human colon carcinomas is
      available. We investigated the expression of 10 of the 12 genes in human colon
      tissue. DESIGN: Eighty pairs of tumor and normal tissue samples from the human
      colon were studied by means of reverse transcription-polymerase chain reaction.
      RESULTS: None of the genes was expressed in the 80 control samples of normal
      tissue. On the other hand, expression was recognized in tumor samples, ranging
      from 5% of samples for MAGE-6 to 44% for MAGE-8. Seventy of the 80 tumor samples
      (88%) expressed at least 1 of the 10 MAGE genes. The frequency of liver
      metastasis was significantly higher in cases with tumor samples that expressed
      MAGE-3 than in those that did not express this gene. This tendency was not
      observed for other members of the MAGE gene family. No significant differences
      were observed in the other clinicopathologic factors between any MAGE-positive
      and -negative tumor cases. CONCLUSIONS: The MAGE genes were exclusively expressed
      in carcinoma tissues and not in normal tissues of the colon. The finding that
      nearly 90% of tumors expressed at least one MAGE gene indicates the possible
      clinical use of this gene for both immunotherapy and molecular diagnosis.

PMID- 9625426
TI  - Medullary thyroid carcinoma with a paraganglioma-like pattern and melanin
      production: a case report with ultrastructural and immunohistochemical studies.
AB  - We report a case of medullary thyroid carcinoma with a paraganglioma-like pattern
      and melanin production. Macroscopically, a rectangular black area within a gray
      white background was seen on the cut surface of the tumor. Histologically, the
      tumor was found to have a trabecular or nestlike architecture with many pigmented
      dendritic cells, resembling the "sustentacular cells" of paraganglioma, scattered
      among nonpigmented polygonal tumor cells. Fontana-Masson staining and bleaching
      with potassium permanganate and oxalic acid revealed that this pigment was
      melanin, which was also confirmed by electron microscopy. Immunohistochemically,
      pigmented dendritic cells were positive for calcitonin, as were the surrounding
      typical medullary thyroid carcinoma cells. These cells were also positive for
      S100 protein but not for HMB-45, compatible with sustentacular cells. These
      findings suggest that this tumor could be considered to bridge the gap between
      two variants of medullary thyroid carcinoma, the melanin-producing (pigmented)
      type and the paraganglioma-like type.

PMID- 9625427
TI  - An unusual case associating ileal Crohn's disease and diffuse large B-cell
      lymphoma of an adjacent mesenteric lymph node.
AB  - Intestinal non-Hodgkin's lymphomas are a rare complication of long-standing
      Crohn's disease and generally arise in sites of active inflammatory disease. To
      our knowledge, we report the first case of an unusual association between ileal
      Crohn's disease and a diffuse large B-cell non-Hodgkin's lymphoma involving an
      adjacent mesenteric lymph node but not the intestinal tract. A 22-year-old man
      was seen for intermittent abdominal pain, vomiting, and severe weight loss that
      were suggestive of intestinal obstruction. A segmental ileocolonic resection was
      performed. Gross examination revealed a terminal ileal inflammatory stenosis and
      enlarged mesenteric lymph nodes. Histologically, terminal ileal Crohn's disease
      was associated with a diffuse large cell lymphoma localized within one mesenteric
      lymph node without intestinal involvement. Immunophenotyping performed on
      deparaffinized sections demonstrated the B phenotype of this lymphoma.

PMID- 9625428
TI  - Enlargement of the thymus in a child with chronic granulomatous disease receiving
      interferon gamma therapy.
AB  - Both an enlarged thymus (with normal results on histologic examination) and an
      increase in the percentage of peripheral CD4+CD45RA+ (naive) T lymphocytes
      developed in a child with chronic granulomatous disease receiving long-term
      interferon gamma therapy. The thymic regrowth may be secondary to interferon
      gamma therapy or to overstimulation of his compromised immune system by recurrent
      infections. To our knowledge, an association between enlargement of the thymus
      and either chronic granulomatous disease or interferon gamma has not been
      previously reported.

PMID- 9625429
TI  - Gemcitabine--a safety review.
AB  - Gemcitabine is a novel nucleoside analog with demonstrated efficacy across a
      range of solid tumors. This paper reviews the single-agent safety profiles of 979
      patients in 22 completed clinical studies using a day 1, 8, 15 q 28 day, 800-1250
      mg/m2 dose schedule. Hematological toxicity was mild with WHO grade 3 and 4
      toxicities recorded for hemoglobin (6.8 and 1.3% of patients), leukocytes (8.6
      and 0.7%), neutrophils (19.3 and 6.0%) and platelets (4.1 and 1.1%).
      Myelosuppression was short lived and rarely of clinical significance. Mucositis
      and alopecia were rare, and nausea and vomiting mild. Transient rises in
      transaminases, mild proteinuria and hematuria were common, but rarely clinically
      significant. Renal failure of uncertain etiology was reported in seven instances.
      Some patients (18.9%) experienced transient flu-like symptoms and mild fever was
      reported in 37.3% of flu patients. Peripheral edema was reported in 20.3% of
      patients in the absence of cardiac, hepatic or renal failure. Thus, gemcitabine
      is well tolerated and has a mild toxicity profile. Of nearly 11,000 protocol
      defined injections, 94% were administered and only 14% were reduced. Grade 3 or 4
      non-laboratory toxicities with a frequency of more than 1% were only seen for
      infection (1.2%), nausea and vomiting (18.4%), and pulmonary toxicity (1.4%).

PMID- 9625430
TI  - Phase II study with cisplatin and paclitaxel in combination with weekly high-dose
      24 h infusional 5-fluorouracil/leucovorin for first-line treatment of metastatic
      breast cancer.
AB  - Results from our previous phase II study demonstrating high efficacy and low
      toxicity for a weekly schedule of 5-fluorouracil (5-FU)/leucovorin in intensively
      pretreated patients with metastatic breast cancer prompted addition of paclitaxel
      and cisplatin to this regimen for a phase II study of outpatient first-line
      treatment of metastatic breast cancer. (MBC). Twenty-eight patients with
      metastatic breast cancer have been evaluated. Pretreatment comprised adjuvant CTX
      in 24 out of 28 patients, but no prior CTX for MBC. Patients were treated with 5
      FU 2 g/m2 (24 h infusion) plus leucovorin 500 mg/m2 (2 h infusion prior to 5-FU)
      weekly for 6 weeks (days 1, 8, 15, 22, 29 and 36); in addition, paclitaxel 175
      mg/m2 (3 h infusion) was administered on days 0 and 21, and cisplatin 50 mg/m2 (1
      h infusion) on days 1 and 22 prior to 5-FU/leucovorin, repeated every 50 days.
      All patients were treated as outpatients using Port-a-Cath systems and portable
      pumps. Aside from common total alopecia, neutropenia was common but only of short
      duration. No episodes of febrile neutropenia occurred. Non-hematologic toxicities
      (NCl CTC grade, percent of patients) consisted of mild to moderate diarrhea (2+3,
      47%), mucositis (2, 14%), and nausea and vomiting (2+3, 60%). Out of 28 patients
      with bidimensionally measurable disease 25% (seven out of 28) achieved a CR, 57%
      (16 out of 28) achieved a PR, 11% (three out of 28) had a SD and 7% (two out of
      28) had a PD. Overall RR was 82% (95% confidence interval 66-100%). Median
      remission duration was 8 months, median time to progression 9 months and median
      survival time 28 months with a median follow-up of 21 months. We conclude that
      the combination of paclitaxel, cisplatin and 5-FU/leucovorin is an effective non
      anthracycline-containing regimen for the first-line treatment of MBC.

PMID- 9625431
TI  - The effect of combining antitubulin agents on differentiated and undifferentiated
      human colon cancer cells.
AB  - The cytotoxicity of sequential combinations of a taxoid [paclitaxel (TAX) or
      docetaxel (TXT)] with a vinca alkaloid [vinorelbine (NVB)] was compared in
      differentiated and undifferentiated HT29-D4 cells. Agents were titrated from low
      doses inducing no modification of microtubule network to high doses corresponding
      to the clinically relevant concentrations that block mitosis. For
      undifferentiated cells, the sequential combination NVB/TAX was more efficient
      than TAX/NVB (22% cell survival versus 37% for 5 nM TAX and NVB). Surprisingly,
      we successively obtained synergism for low doses of both compounds [NVB (1-5 nM)
      and TAX (1-15 nM)], then additivity and finally antagonism when one of the
      compounds was at the concentration inducing mitotic block. The three patterns of
      results were also obtained with NVB/TXT combinations. For the synergistic
      combinations at the lowest concentrations, cytotoxicity occurred by apoptosis
      following mitosis. For differentiated cells, the most cytotoxic combinations were
      1 microM TAX or TXT for 3 days followed by 1 microM NVB for 3 days, and 0.75 nM
      TAX or TXT for 9 days followed by 1 microM NVB for 3 days, the latter producing
      synergistic effects. Cytotoxicity occurred by apoptosis for the two states of
      differentiation. Major differences depending on cell phenotype were demonstrated:
      low sensitivity of differentiated cells to antitubulin agents and the difference
      in apoptotic pathways since mitosis is not involved in differentiated cells.

PMID- 9625432
TI  - Determination of unbound platinum after oxaliplatin administration: comparison of
      currently available methods and influence of various parameters.
AB  - Variations in plasma protein binding may have profound effects on both
      disposition and activity of drugs, especially for those which are tightly bound
      to proteins, such as anticancer platinum derivatives. Methods of separation of
      the non-protein-bound fraction and some technical parameters may influence the
      results. We have compared ultrafiltration and ultracentrifugation, as well as the
      effect of potentially interfering factors, upon the determination of the plasma
      unbound platinum fraction after oxaliplatin administration to cancer patients.
      Ultrafiltration and ultracentrifugation provided very closely correlated results,
      so that either technique can be used. The ultrafiltration cut-off (3000-30,000
      Da) devices, the type of tube for blood sampling and the type of anticoagulant
      (none, lithium heparinate or EDTA) did not influence the results markedly. In
      contrast, results were greatly influenced by freezing: erratic results were
      obtained on thawed plasmas when compared with those on fresh serum or plasma.
      Consequences may be important in usual practice, since many pharmacokinetic
      studies are carried out in multicentric trials with plasma processing centralized
      in one reference laboratory. The methods for the determination of protein-drug
      binding should be standardized and guidelines elaborated where optimal conditions
      for each type of binding assay are given.

PMID- 9625433
TI  - Cytotoxic effect of interferon-alpha2a in combination with all-trans retinoic
      acid or cisplatin in human ovarian carcinoma cell lines.
AB  - Ovarian cancer has a poor prognosis due to the frequent appearance of a drug
      resistant state. An alternative therapeutic approach may lie in combinations of
      conventional chemotherapeutic agents with new classes of drug, such as
      interferons (IFN) and differentiation-inducing agents. There is clinical evidence
      that both IFN-alpha2a-all-trans retinoic acid (ATRA) and IFN-alpha2a-cisplatin
      have significant activities on growth of malignant cells, cell differentiation or
      programmed cell death in solid tumors. In order to throw more light on the
      cellular basis of these findings and to optimize a schedule of such drug
      combinations, we examined the cytotoxic effects of various combinations on five
      human ovarian carcinoma cell lines. The experiments were based on a clonogenic
      assay on plastic. The different cell lines exhibited different sensitivities to
      the three drugs tested. Using the cell line most sensitive to these drugs, we
      then examined the effect of different sequences of two drug combinations. We
      observed a potentiation after pretreatment with ATRA followed by IFN-alpha2a and
      ATRA or after pretreatment with IFN-alpha2a followed by IFN-alpha2a and
      cisplatin. Using this schedule of administration, cytotoxic interactions between
      the two drugs were investigated by median effect analysis. Synergism or
      antagonism were observed depending on the intrinsic sensitivity of the cell line
      to the first drug and the concentrations used. The magnitude of these
      interactions was found to be influenced by the cellular sensitivity to the second
      drug. These results show that schedules of drug combinations are not easy to
      design and may help account for the various failures and the discrepant effects
      observed in clinical trials.

PMID- 9625434
TI  - Synthesis, characterization and nitric oxide release profile of
      nitrosylcobalamin: a potential chemotherapeutic agent.
AB  - Nitrosylcobalamin, a vitamin B12-based, non-toxic carrier of nitric oxide (NO),
      has been synthesized, isolated and characterized in vitro. A UV/Vis analysis was
      performed confirming the reduction of the cobalt atom of hydroxocobalamin
      (vitamin B12a) with the binding of NO, causing a shift in the absorption spectra
      of CO3+ (lambdamax=530) to CO2+ (lambdamax=500) with the formation of
      nitrosylcobalamin. The extinction coefficient (epsilonmax) of nitrosylcobalamin,
      as calculated, was 4.8 (mM(-1), cm(-1)). An IR analysis determined the v(NO)
      vibrational frequency at 1652 cm(-1), supporting the binding of NO and suggesting
      a bent bonding geometry. NO release was maximized utilizing acidic conditions (pH
      4.9, 32 degrees C) with a cumulative release of about 4610 nmol of NO in 675 h
      (calculated half-life of 210 h), representing 39% NO loading based on 11,890 nmol
      NO, theoretically possible (one NO per molecule of hydroxocobalamin). The
      cumulative NO release followed first-order kinetics and was pH dependent. NO
      release was minimal at pH 6.0 and 7.4 (37 degrees C), and undetected at pH 10 (37
      degrees C). The possibility for nitrosylcobalamin to deliver NO (the active
      chemotherapeutic agent) to neoplastic cells is suggested because tumor cells,
      specifically leukemia cells, possess surface cell receptors for vitamin B12 which
      is readily utilized in the cellular proliferation process. Nitrosylcobalamin may
      offer a 'drug targeting' approach as a potential, biologically compatible and
      selective chemotherapeutic agent.

PMID- 9625435
TI  - Transcriptional down-regulation of c-myc expression in an erythroleukemic cell
      line, K562, and its doxorubicin-resistant variant by two topoisomerase II
      inhibitors, doxorubicin and amsacrine.
AB  - We have evaluated the effect of two topoisomerase II (Topo II) poisons, amsacrine
      and doxorubicin, on the expression of the c-myc oncogene, both at the mRNA and
      protein levels, in the leukemia cell line, K562, and its doxorubicin-resistant
      counterpart, K562 DoxR. We report in this study a concentration-dependent
      decrease in c-myc mRNA levels upon exposure of both cell lines to amsacrine and
      doxorubicin, with a more pronounced effect for amsacrine in the resistant line.
      In either case, c-myc down-regulation closely paralleled the drug-induced growth
      inhibition. We have also used the technique of PCR stop-assay to detect the
      occurrence of DNA breaks within the P2 promoter of the c-myc gene. We have shown
      that Topo II-mediated breaks induced by amsacrine are probably responsible for
      the down-regulation of c-myc in the resistant line. In addition, amsacrine
      induced apoptosis only in the resistant line while doxorubicin did not induce
      apoptosis in any cell line. These results suggest that c-myc is not involved in
      the resistance of K562 DoxR cells, but can induce the apoptosis pathway in these
      cells, while no drug-induced apoptosis could be detected in the sensitive line.

PMID- 9625436
TI  - The bisbenzylisoquinoline alkaloids, tetrandine and fangchinoline, enhance the
      cytotoxicity of multidrug resistance-related drugs via modulation of P
      glycoprotein.
AB  - The occurrence of resistance to chemotherapeutic drugs is a major problem for
      successful cancer treatment and reducing drug accumulation by P-glycoprotein (P
      gp) is one of the major mechanisms of multidrug resistance (MDR). The present
      study was performed to evaluate the MDR-reversal abilities of two
      bisbenzylisoquinoline alkaloids, tetrandine (TET) and fangchinoline (FAN),
      compared with verapamil (VER), a well-known P-gp modulator. TET (3.0 microM), FAN
      (3.0 microM) and VER (10.0 microM) reduced the paclitaxel (TAX) concentration
      required to achieve 50% inhibition of cell growth (EC50) to HCT15 (P-gp-positive)
      cells about 3100-, 1900- and 410-fold, and these compounds also reduced the EC50
      value of actinomycin D (AMD) about 36.0-, 45.9- and 18.2-fold in the cells,
      respectively. Meanwhile, TET, FAN and VER had no effect on the cytotoxicity of
      the drugs to SK-OV-3 (P-gp-negative) cells. On the other hand, TET (3.0 microM),
      FAN (3.0 microM) and VER (10.0 microM) similarly enhanced the accumulation rates
      of rhodamine 123, a well known P-gp substrate, in HCT15 cells (200-250%). After
      efflux for 2 h with fresh medium, TET and FAN also enhanced the residual rate of
      rhodamine 123 about 5.0- and 2.6-fold in comparison with control, respectively.
      TET, FAN and VER could not affect the accumulation and residual rate of rhodamine
      123 in SK-OV-3 cells. From the result, we conclude that TET and FAN enhanced the
      cytotoxicity of MDR-related drugs via modulation of P-gp.

PMID- 9625437
TI  - Antitumor activity of KW-2170, a novel pyrazoloacridone derivative.
AB  - 5-(3-Aminopropyl)amino-7,10-dihydroxy-2-(2-hydroxethyl)-aminoethyl -6H
      pyrazolo[4,5,1-de]acridin-6-one dihydroxy-chloride (KW-2170), a novel derivative
      of pyrazoloacridone, was selected and evaluated for its antitumor activity and
      toxicity in mice. KW-2170 exhibited antitumor activity superior to adriamycin
      (ADM) against Sarcoma 180, breast carcinoma MM102 and fibrosarcoma Meth A
      inoculated s.c. in mice. Its therapeutic index (LD10/ED50) was higher than that
      of ADM on two murine carcinoma models, MM102 and Meth A. KW-2170 showed
      significant antitumor activity against 17 human tumor xenografts of a total of 24
      tumors tested and the total tumor response rate by treatment with KW-2170 was
      significantly higher than that by ADM (70.8 versus 58.3%). In particular, human
      lung carcinoma was highly sensitive to KW-2170, and a marked tumor regression was
      observed on Lu-65 and Lu-99 human lung carcinoma xenograft models. Ovary and
      pancreas carcinomas were also sensitive to the drug. Additionally, its
      therapeutic index was also high on these human carcinoma models in comparison
      with that of ADM. The best antitumor efficacy of KW-2170 was observed by a weekly
      treatment schedule followed by a single treatment schedule and a successive
      administration schedule also tended to be toxic to the hosts. KW-2170 exhibited
      very low cross-resistance against four lines of multidrug resistant tumors
      expressing high levels of P-glycoprotein, and the drug showed significant
      antitumor activity against ADM-resistant human ovary carcinoma A2780/ADM and
      against nasopharynx carcinoma KB-A1 xenografts which were not sensitive to ADM.
      These results indicate that KW-2170 has a very potent antitumor activity and is
      feasible as a new antitumor drug against ADM-refractory solid tumors in clinics.

PMID- 9625438
TI  - ONO-4007 induces specific anti-tumor immunity mediated by tumor necrosis factor
      alpha.
AB  - We investigated the therapeutic effects of ONO-4007, a novel synthetic lipid A
      derivative with low toxic activities, on transplanted hepatocellular carcinoma
      KDH-8 in WKAH rats. ONO-4007 brought about complete cures in about 60% of rats
      bearing tumor necrosis factor (TNF)-alpha-sensitive KDH-8 cells, whereas no
      complete cure was observed in rats bearing cKDH-8/11 which is identical to KDH-8
      but a TNF-alpha-resistant cell line, KMT-17 and KEG-1. Then we examined the
      influence of rabbit anti-TNF-alpha antibody on the therapeutic effects of ONO
      4007 against the TNF-alpha-sensitive KDH-8. The concomitant administration of the
      rabbit anti-TNF-alpha antibody completely abrogated the therapeutic effects of
      ONO-4007. On the other hand, rechallenged tumor cells of both KDH-8 and cKDH-8/11
      were completely rejected in the rats cured of KDH-8 tumor, although no rejection
      of KEG-1 was observed. Moreover, Winn assay, i.e. the tumor cell neutralizing
      assay, indicated that CD4+ T cells were involved in the antigen-specific
      transplantation resistance. These findings suggest that antigen-specific T cell
      responses are involved in the complete cure of tumors after the treatment with
      ONO-4007, although its therapeutic effect is initiated by TNF-alpha.

PMID- 9625439
TI  - Prolonged remission of endometrial cancer with paclitaxel and carboplatin.
AB  - Recurrent endometrial cancer has grave prognosis. Chemotherapy and hormonal
      therapy are mainstays of palliative treatment. Unfortunately the frequency of
      complete response and duration of progression-free interval are limited. This
      case report describes a patient with recurrent metastatic endometrial cancer who
      was initially treated with radiotherapy followed by surgery. Her recurrent tumor
      progressed during treatment with external radiation and a progestogen. She
      received paclitaxel (135 mg/m2 i.v. infusion over 24 h) and carboplatin (AUC 7.5
      microg x h/ml) every 4 weeks with complete remission after 8 months which has
      persisted for 22 months. Paclitaxel and carboplatin combination should be
      considered for the treatment of endometrial cancer.

PMID- 9625440
TI  - Therapeutic effects of 5-fluorouracil microspheres on peritoneal carcinomatosis
      induced by Colon 26 or B-16 melanoma in mice.
AB  - The delivery formulation 5-FU-MS [5-fluorouracil (5-FU) incorporated in
      microspheres composed of a poly(glycolide-co-lactide) matrix] slowly releases 5
      FU over 3 weeks. 5-FU-MS delivers higher concentrations of the drug to the i.p.
      tissues for a longer period of time with lower blood plasma concentrations than
      does an aqueous 5-FU solution and reduces toxicity. In this study, we evaluated
      the therapeutic effects of 5-FU-MS on peritoneal carcinomatosis in mice. Four
      days after an i.p. inoculation with Colon 26 or B-16 PC melanoma, 5-FU at 200
      mg/kg was administered i.p. as 5-FU-MS or as an aqueous solution of 5-FU. 5-FU-MS
      extended the survival of mice bearing Colon 26 or B-16 PC melanoma significantly
      better than the equivalent dose of aqueous 5-FU solution.

PMID- 9625441
TI  - Effects of oil-soluble organosulfur compounds from garlic on doxorubicin-induced
      lipid peroxidation.
AB  - Clinical efficacy of doxorubicin is compromised due to free radical generation
      leading to cardiac toxicity. Oil-soluble organosulfur compounds, diallyl sulfide
      (DAS), diallyl disulfide (DADS), dipropyl sulfide (DPS) and dipropyl disulfide
      (DPDS), present in garlic were examined for their antiperoxidant effects. DADS
      inhibited liver microsomal lipid peroxidation induced by NADPH, ascorbate and
      doxorubicin. DAS, DPS and DPDS were ineffective inhibitors of liver microsomal
      lipid peroxidation. DADS could be used in combination with doxorubicin to protect
      oxidative injuries to improve the clinical efficacy of doxorubicin.

PMID- 9625442
TI  - AP-1-like motif as a key to understanding the insulin-like growth factor I (IGF
      I) gene regulation.

PMID- 9625443
TI  - Cellular and extracellular regulatory mechanisms of hypothalamic corticotropin
      releasing hormone neurons.

PMID- 9625444
TI  - Expression of fibroblast growth factor-2 and fibroblast growth factor receptor-1
      in thyroid diseases: difference between neoplasms and hyperplastic lesions.
AB  - We studied the expression of both fibroblast growth factor-2 (FGF-2) and FGF
      receptor-1 (FGFR-1) in various histological types of human thyroid neoplastic and
      hyperplastic tissues to clarify the biological behavior of FGF-2. A total of 37
      malignant tumors (24 papillary carcinomas, 10 follicular carcinomas, 3 anaplastic
      carcinomas), 8 follicular adenomas, and 12 adenomatous goiters were examined by
      immunohistochemical methods. With immunohistochemical staining, both FGF-2 and
      FGFR-1 were frequently detected in human thyroid carcinoma (79.2 to 100% and 80
      to 100%, respectively). In thyroid hyperplastic lesions such as adenomatous
      goiter, the FGF-2 immunoreactivity in follicular cells was detected in 2 of 12
      adenomatous goiters (16.7%). In contrast, FGFR-1 immunoreactivity was detected in
      66.7% of cases of this disease. The endothelial cells of microvessels in the
      stroma adjacent to the neoplasms and hyperplastic lesions also showed cytoplasmic
      FGF-2 immunoreactivity. The difference between FGF-2 and FGFR-1 expression in
      adenomatous goiters was statistically significant (P<0.05). Furthermore, the
      difference in FGF-2 immunoreactivity between carcinoma and adenomatous goiter was
      statistically significant (P=0.0001). The present investigation demonstrated the
      possibility of an autocrine mechanism of action of FGF-2 in human thyroid
      carcinoma. Moreover, in thyroid hyperplastic lesions, FGF-2 derived from the
      stroma might be involved in the formation of nodular and/or diffuse goiters.

PMID- 9625445
TI  - Serum concentration of the pyridinoline cross-linked carboxyterminal telopeptide
      of type I collagen (ICTP) is a useful indicator of decline and recovery of bone
      mineral density in lumbar spine: analysis in Japanese postmenopausal women with
      or without hormone replacement.
AB  - To reassess the clinical utility of serum pyridinoline cross-linked
      carboxyterminal telopeptide of type I collagen (ICTP), a promising but
      controversial indicator of bone resorption, we evaluated its performance as a
      biochemical marker in a 6-month study of a strictly selected population of 76
      Japanese postmenopausal and healthy women, 33 recipients of hormone replacement
      therapy and 43 nonrecipients. We measured bone mineral density (BMD) of the
      lumbar spine (L2-L4), and serum ICTP, carboxyterminal propeptide of type I
      procollagen (PICP) and other conventional serum biochemical markers, e.g. bone
      gla protein (BGP), alkaline phosphatase, calcium and phosphate at the entry and 6
      months later. We calculated the percent change between the baseline and 6-month
      values (delta%) in lumbar BMD and the biochemical markers, individually, and
      compared the degree of correlations between delta% in BMD and that in the
      biochemical markers. Delta% in ICTP and delta% in BGP correlated with delta% in
      BMD negatively and significantly. Especially delta% in ICTP correlated with that
      in BMD to a high degree (P<0.0001). No significant correlation was observed in
      other biochemical markers. We concluded that serum ICTP is a sensitive and useful
      bone resorption marker in the postmenopausal population, which strongly
      correlates with the change in BMD.

PMID- 9625446
TI  - Intrahypothalamic perfusion of KP102 stimulates growth hormone release in goats.
AB  - The hypothalamic actions of KP102 (also called GHRP-2) on the release of GH were
      studied in female goats. KP102 (10(-5) M) was perfused into the goat hypothalamus
      through a microdialysis probe (CMA/10 probe with a 4 mm membrane length) at a
      rate of 4 microl/min for 90 min, and plasma GH concentrations before and after
      perfusion were measured. The intrahypothalamic perfusion of 10(-5) M KP102
      significantly stimulated GH release in goats (P<0.05). The GH levels began to
      rise after commencement of perfusion, and reached a maximum mean value at 180
      min. The concentrations of GH at 165, 180, 195, 210, 225 and 240 min after
      commencement of perfusion of KP102 were significantly higher than the
      corresponding values for control animals (P<0.05). KP102 had no effect on GH
      pulse frequency, but it significantly increased the GH pulse amplitude after the
      perfusion (P<0.05). In contrast to KP102, intrahypothalamic perfusion of 10(-5) M
      GHRH had no effect on the stimulation of GH release in goats even if intravenous
      injection of 10(-5) M GHRH significantly stimulated GH release (P<0.05). These
      results suggest that KP102 may act partly on the hypothalamus to stimulate GH
      release in goats.

PMID- 9625447
TI  - Hyperfunctioning thyroid adenoma concomitant with papillary thyroid carcinoma,
      follicular thyroid adenoma and primary hyperparathyroidism.
AB  - A case of 67-year-old woman with hyperthyroidism due to functioning thyroid
      adenoma is reported. The patient had concomitant follicular thyroid adenoma and
      primary hyperparathyroidism in addition to functioning adenoma. Histological
      examination of the excised thyroid tissue revealed occult papillary carcinoma
      within a functioning adenoma. Genetic analysis of such tumors indicated that
      functioning adenoma and papillary carcinoma may be etiologically independent.
      There have been a number of case reports on the coexistence of functioning
      thyroid adenoma and thyroid cancer or hyperparathyroidism, but none of the
      studies had examined the etiologic relationship of these lesions on a genetic
      basis. Furthermore, to our knowledge, this is the first report of the concurrence
      of four tumors in the neck, functioning thyroid adenoma, papillary thyroid
      carcinoma, follicular thyroid adenoma and parathyroid adenoma.

PMID- 9625448
TI  - Saireito (a Chinese herbal drug) decreases inhibitory effect of prednisolone and
      accelerates the recovery of rat hypothalamic-pituitary-adrenal axis.
AB  - Saireito, a saiko agent (a Chinese herbal drug), increases the synthesis and
      secretion of ACTH by stimulating hypothalamic CRH release. In the present study,
      we examined the effect of food containing saireito (1.5%) on the recovery of the
      hypothalamic-pituitary-adrenal axis after treating male rats with prednisolone
      (PSL, 200 microM) in drinking water for 14 days. Saireito was administered during
      and after PSL administration. The rats were decapitated at various times after
      PSL administration. Tail-pinch stress had been applied to some rats. The plasma
      ACTH response to tail-pinch stress in the PSL + saireito group recovered to the
      control level on day 1, but that in the group given PSL alone recovered on day 3.
      The ACTH level in the anterior pituitary and the CRH level in the median eminence
      of the PSL + saireito group returned to the control level on day 3, and that in
      the group given PSL alone returned to it on day 5. These results indicate that
      the administration of saireito reduces the negative feedback effect of PSL on the
      hypothalamus and pituitary and accelerates the recovery of the hypothalamic CRH
      and pituitary ACTH level after glucocorticoid treatment.

PMID- 9625449
TI  - Atrial natriuretic peptide has no potential to protect against endotoxin-induced
      acute renal failure in the absence of renal nerves.
AB  - Atrial natriuretic peptide (ANP) has been shown to have the potential to restore
      renal function after ischemic injury, an underlying component of endotoxin (Et)
      induced acute renal failure, and is known to counteract renal sympathetic nerve
      activity in renal function. We have recently found that renal denervation
      restores the Et-induced renal dysfunction. The purpose of this study was to
      examine effects of ANP infusion on the Et-induced acute renal failure in the
      absence of renal nerves. Ten to 14 days after bilateral renal denervation (DNX),
      Wistar rats (250 to 300 g body wt) were used in the acute experiment. Rats with
      intact renal nerves (INN) served as controls. Following control clearance
      measurements, rats were intravenously injected with 4 mg/kg Et (Escherichia coli,
      055: B5). During endotoxemia, rats were infused with 10 microg/kg/h ANP or saline
      vehicle. Et injection reduced the glomerular filtration rate (GFR) significantly
      in saline-infused INN and DNX rats. ANP infusion restored the greatly reduced GFR
      to the pre-endotoxemia level in DNX rats but not in INN rats. There was
      significant difference between the ANP- and saline-infused DNX rats in the
      percentage change relative to the basal GFR value during the ANP infusion period.
      ANP infusion did not improve the hyponatriuresis and oliguria after Et
      administration, which is independent of renal nerves. In conclusion, ANP infusion
      has a minor reno-protective effect in rats with Et-induced acute renal failure in
      the absence of the renal nerves.

PMID- 9625450
TI  - Platelet epidermal growth factor in thyroid disorders.
AB  - We evaluated the concentration of epidermal growth factor (EGF) in platelets,
      serum and plasma obtained from 47 patients with Graves' disease, 7 with
      hypothyroidism and 20 healthy subjects. The platelets of the subjects were
      collected from platelet rich plasma and lysed by freezing and thawing.
      Subsequently the platelet debris was treated with Triton X-100. The EGF
      concentration was determined by homologous radioimmunoassay. The concentration of
      EGF in the platelets in 14 patients with untreated Graves' disease was
      significantly higher than that in the healthy controls. After treating these 14
      patients with antithyroid agents, the EGF concentration in the platelets
      decreased to the level of the healthy controls. The EGF concentration in the
      platelets in the 7 untreated hypothyroid patients decreased after replacement
      therapy with thyroxine. The mean volume of the platelets in the 14 patients with
      untreated Graves' disease was significantly larger than in the control and
      decreased after treatment with antithyroid agents. The serum and plasma levels of
      EGF in the 7 untreated hypothyroid increased after replacement therapy. In
      conclusion, thyroid function affected the concentration of EGF in the platelets
      of patients with thyroid disorders.

PMID- 9625451
TI  - Immunohistochemical study of cytochrome b5 in human adrenal gland and in
      adrenocortical adenomas from patients with Cushing's syndrome.
AB  - Cytochrome b5, a component of the electron transfer system increases the relative
      activity of 17,20-lyase to 17alpha-hydroxylase of P450c17 in vitro. In the
      present study, immunohistochemical analysis of cytochrome b5 was performed in the
      human adrenal gland and in adrenocortical adenomas from patients with Cushing's
      syndrome. In the human adrenal gland, cytochrome b5 was stained in all three
      adrenocortical layers but the staining was most remarkable in the zona
      reticularis. All of the adenomas were composed mainly of compact cells, which
      exhibited immunoreactive staining for cytochrome b5 as well as for P450c17 and
      3beta-hydroxysteroid dehydrogenase (3beta-HSD). The distribution of b5 in the
      adenomas was correlated with that of P450c17 rather than with that of 3beta-HSD.
      The immunoreactive staining for cytochrome b5 appeared to be more prominent in
      the two adenomas that produced relatively high concentrations of adrenal
      androgens than in adenomas that produced low concentrations of adrenal androgens.
      These results immunohistochemically support the functional association of b5 with
      androgen production through interaction with P450c17 and the previous finding
      that higher concentrations of cytochrome b5 are associated with greater
      production of adrenal androgens in adrenocortical adenomas from patients with
      Cushing's syndrome.

PMID- 9625452
TI  - Comparison of markers of bone formation and resorption in prostate cancer
      patients to predict bone metastasis.
AB  - We investigated the usefulness of two biochemical markers of bone formation
      (PICP, the carboxy-terminal propeptide of type I procollagen, and bone ALP, bone
      derived alkaline phosphatase) and a marker of bone resorption (ICTP, the carboxy
      terminal telopeptide of type I collagen), to determine whether the presence of
      bone metastasis in prostate cancer could be evaluated and the extent of bone
      metastasis could be stratified by the serum levels of these markers, compared to
      total alkaline phosphatase (T-ALP) and prostate-specific antigen (PSA). The serum
      levels of PICP, bone ALP, ICTP, T-ALP and PSA were significantly higher in
      patients with both prostate cancer and bone metastasis (n=49) than in patients
      with benign prostatic hyperplasia (n=35) and patients with prostate cancer
      without bone metastasis (n=70). The superiority of a marker in the rate of
      detection of bone metastasis was evaluated with receiver operating characteristic
      curves. The serum marker levels were compared as a function of metastatic burden
      in bone (i.e., the extent of disease, EOD grade). We found that bone ALP is the
      most suitable marker for evaluating bone metastasis, especially for stratifying
      the degree of bone metastasis. Both PICP and ICTP were useful in this respect,
      but rather inferior to bone ALP. T-ALP had the lowest ability for detecting bone
      metastasis, but its correlation with the EOD grade was excellent, second to that
      of bone ALP. PSA showed limited reliability for stratifying the extent of bone
      metastasis.

PMID- 9625453
TI  - A new point mutation (3426, A to G) in mitochondrial NADH dehydrogenase gene in
      Korean diabetic patients which mimics 3243 mutation by restriction fragment
      length polymorphism pattern.
AB  - Mitochondrial tRNA(Leu)(UUR) gene mutation is one of the candidates in the
      pathogenesis of NIDDM. Especially the 3243 (A-->G) mutation is associated with
      the maternally-inherited diabetes and deafness. To evaluate the prevalence and
      characteristics of the 3243 point mutation in Koreans, we screened 433 Korean
      diabetic patients (220 men and 213 women). Genomic DNA was extracted from
      peripheral white blood cells and PCR was carried out with mitochondrial DNA
      primers (3130-3149, 3558-3539) encompassing the 3243 position. After digestion
      with Apa-1, five subjects showed polymorphism suggesting 3243 point mutation but
      when we directly sequenced the amplified DNA with an automatic sequencer, only 2
      of the 5 patients were shown to have 3243 (A-->G) mutation and the other 3
      subjects had 3426 (A-->G) mutation rather than 3243 mutation. Two diabetic
      patients with 3243 mutation were lean (BMI = 14.4, 17.0 kg/m2), had relatively
      lower fasting C-peptide concentrations (0.9 ng/ml each), and required insulin for
      management. In contrast, those with 3426 point mutation were not lean (BMI = 22.6
      28.0 kg/m2), had relatively higher C-peptide levels (3.9-5.4 ng/ml), and could be
      managed with oral hypoglycemic agents. None of the 5 patients had deafness. In
      conclusion, the prevalence of 3243 point mutation in Korean diabetic patients was
      approximately 0.5% and we found a new mutation mimicking 3243 mutation by PCR
      RFLP (restriction fragment length polymorphism) pattern. We suggest that
      sequencing of the PCR product or designing smaller PCR fragment size to enhance
      the specificity may help to identify the exact location of the point mutation.

PMID- 9625454
TI  - Occult papillary thyroid carcinoma in Hashimoto's thyroiditis presenting as a
      metastatic bone tumor.
AB  - Some occult thyroid carcinomas are hypothesized to regress and be eventually
      obliterated. We report here a patient whose condition supports this hypothesis. A
      51-year-old male with primary hypothyroidism due to Hashimoto's thyroiditis
      suffered from a rib bone tumor. He had a diffuse goiter with no nodular lesion.
      Serum FT4 and TSH concentrations were 0.8 ng/dl and 36.4 microU/ml on taking 100
      microg/day of T4. Anti-Tg- and -TPO-Ab were strongly positive (99 and 1380 U/ml).
      The iodine 123 scintigraphy demonstrated clear accumulation in the rib tumor,
      whereas the thyroid was scarcely visible. Biopsy of the rib tumor showed
      papillary proliferation of large atypical cells, which were immunohistochemically
      positive for thyroglobulin. Metastatic bone tumor of papillary thyroid carcinoma
      was therefore strongly suspected. He underwent a total thyroidectomy and the
      thyroid was stepwise sectioned completely at 3 mm intervals. The thyroid
      condition was diagnosed as Hashimoto's thyroiditis demonstrating diffuse and
      dense fibrosis, lymphocyte infiltration with lymphoid follicles and flattened
      atrophied follicles, but no carcinomatous foci were found. He was treated with I
      131 and scintigraphy after the ingestion showed distinct accumulation in the rib
      tumors similar to that before thyroidectomy. No other abnormal uptake was
      observed. It is suggested that the primary occult thyroid papillary carcinoma
      regressed and was obliterated possibly by some immunologic or other host
      resistance factors after it metastasized to the distant bone.

PMID- 9625455
TI  - Hyperthyroid Graves' disease and primary hypothyroidism caused by TSH receptor
      antibodies in monozygotic twins: case reports.
AB  - A 33-year-old woman with signs and symptoms of hypothyroidism, including
      increased thyroid stimulating blocking antibody (TSBAb) activity, was referred
      for treatment by her local physician. Her monozygote twin was treated for
      hyperthyroid Graves' disease 10 years earlier. This case of hyperthyroidism and
      hypothyroidism in identical twins suggests the involvement of environmental
      factors in the pathogenesis of autoimmune thyroid diseases.

PMID- 9625456
TI  - Vitamin D receptor genotype is associated with cortical bone loss in Japanese
      patients with primary hyperparathyroidism.
AB  - Vitamin D receptor (VDR) genotype was determined in 66 Japanese patients with
      primary hyperparathyroidism (pHPT). In contrast to previous report showing an
      association between VDR genotype bb and the development of pHPT in a Swedish
      population, we did not find any differences in the frequencies of the VDR
      genotypes between pHPT and the control. The bone mineral density in the radius
      was significantly lower (Z score, -1.723 +/- 1.819) in bb genotype than in BB/Bb
      genotype (+0.255 +/- 2.344) in pHPT patients. Based on the fact that PTH requires
      vitamin D3 to take effect on calcium mobilization from bone, it is possible that
      VDR polymorphism may influence the PTH action on bone.

PMID- 9625457
TI  - Interleukin-1beta administered intracerebroventricularly stimulates the release
      of noradrenaline in the hypothalamic paraventricular nucleus via prostaglandin in
      the rat.
AB  - We evaluated the effect of intracerebroventricular (i.c.v.) administration of
      interleukin (IL)-1beta on the rectal temperature and the release of noradrenaline
      (NA) in the hypothalamic paraventricular nucleus (PVN) of the rat. IL-1beta
      increased rectal temperature at doses ranging from 300 pg to 300 ng, whereas it,
      at doses ranging from 3 ng to 300 ng, significantly stimulated the release of NA
      in the PVN measured by intracerebral microdialysis. The stimulatory effect of IL
      1beta on the release of NA was blocked by the subcutaneous injection of
      indomethacin. These findings suggest that IL-1beta stimulates the release of NA
      in the PVN via prostaglandin, and that the release of NA in the PVN is not
      necessarily related to the increase in body temperature.

PMID- 9625458
TI  - Abnormal FSH hypersecretion as an endocrinological manifestation of POEMS
      syndrome.
AB  - Two patients with POEMS syndrome had high basal levels of FSH in the absence of
      primary hypogonadism. They were fertile eugonadal men with normal serum
      testosterone and estradiol levels. Provocation with LH-releasing hormone revealed
      blunted response of FSH secretion, but normal response of LH secretion in both
      patients, and one had pituitary microadenoma on brain MRI. This report adds
      primary FSH hypersecretion in the absence of primary testicular failure to the
      list of endocrinopathy of POEMS syndrome.

PMID- 9625459
TI  - Subacute thyroiditis after hepatitis B vaccination.

PMID- 9625460
TI  - Endoscopic thyroidectomy in a porcine.

PMID- 9625461
TI  - Homologous plasma-stored tendon grafting in equids--gross and histomorphological
      observations.
AB  - The efficacy of homologous plasma-stored tendon grafting in the superficial
      digital flexor tendon severed in the mid-metacarpal region was evaluated in 10
      donkeys. Experimental tenectomies were performed, followed by grafting using
      plasma-stored tendon and human amniotic membrane encasement in group I (n=8) but
      no grafting or encasement in group II (control) (n=2). Gross observations in
      group I showed no peritendinous adhesions, except in one animal, while control
      animals showed thick fibrous adhesions and thickening at both the cut ends.
      Histologically, in the grafted tendon there was normal healing tissue at the
      junctional sites with negligible collagen fibre and mild regressing inflammatory
      reaction by day 15. By day 30 there were a great number of blood vessels but
      without any inflammatory reaction. The healing tissue at the grafted site and the
      adjoining paratenon was more mature. The fibroblastic activity appeared to be
      both extrinsic and intrinsic in origin. By day 60 fibroblastic activity was
      negligible and the healing tissue at the distal graft and host tendon junction
      site was at a more advanced stage of maturation and showed early fasciculi/bundle
      formation. Healing tissue at three months showed collagen fibres fasciculi/bundle
      comparable to normal tendon architecture. Tendon appeared histologically normal
      at four months after grafting.

PMID- 9625462
TI  - The influence of sugar-beet fibre, guar gum and inulin on nutrient digestibility,
      water consumption and plasma metabolites in healthy Beagle dogs.
AB  - The aim of the present study was to evaluate the effects of three fibres (sugar
      beet fibre, guar gum and inulin) incorporated in the basal diet of healthy dogs
      at 7 per cent of dry matter (DM). Parameters examined included stool output,
      water consumption, nutrient digestibility and fasting and postprandial plasma
      metabolites. All fibres increased wet faecal output; an increase in faecal DM
      output being observed with sugar-beet fibre only. Sugar-beet fibre and inulin
      increased daily water consumption. Sugar-beet fibre and guar gum decreased DM
      digestibility. The three fibres diminished organic matter and crude protein
      digestibility while ether extract digestibility was decreased by guar gum and
      inulin. Guar gum induced lower postprandial insulin, alpha-amino-nitrogen and
      urea plasma concentrations. Guar gum also lowered fasting cholesterolaemia. Sugar
      beet fibre and inulin showed no metabolic effects. These physiological properties
      suggest that guar gum would be a suitable ingredient for dietary therapy of
      chronic diseases such as diabetes mellitus or hyperlipidaemia in the dog.

PMID- 9625463
TI  - Argyrophilic nucleolar organiser regions (AgNORs) count as indicator of post
      surgical prognosis in feline mammary carcinomas.
AB  - Feline mammary carcinomas (FMC) were surgically resected from 51 cats to verify
      that the nucleolar organiser regions (AgNORs) count is related to the post
      surgical survival time (PST). After one year post-surgery, 27 cats (group A) were
      still alive (52.9 per cent) while (41.7 per cent) (group B) had died as a
      consequence of FMC. Formalin-fixed, paraffin wax-embedded histological sections
      were stained with silver nitrate and the AgNORs were then counted at x 100 oil
      immersion objective. In FMC AgNORs count ranged from 1.2 to 12.1 (6.10+/-2.3). A
      statistically significant difference (P=0.000112) in the AgNORs count was found
      between cats from group A and group B. No other statistically significant
      differences were found between group A and B. AgNORs count was not correlated to
      age or different histological type, according to the WHO classification. Using
      this technique it is possible to identify two populations of FMC with a
      statistically significant difference in the PST.

PMID- 9625464
TI  - Comparative field evaluation of divided-dosing and reduced feed intake upon
      treatment efficacy against resistant isolates of Teladorsagia circumcincta in
      sheep and goats.
AB  - The effects of modifying drug administration and food intake upon the efficacy of
      fenbendazole against resistant isolates of Teladorsagia (Ostertagia) circumcincta
      were investigated using naturally infected sheep and goats. Administration of the
      manufacturer's recommended dose (MRD) as two 2.5 mg kg(-1) bodyweight doses
      divided by a 12-hour interval resulted in an apparent increase in efficacy of
      over 28 per cent compared with conventionally treated sheep. Withholding feed for
      24 hours before treatment at the MRD resulted in respective increases of 39.7 per
      cent (P<0.05) and 25.2 per cent compared with conventionally treated sheep and
      goats. A combination of food withdrawal and divided dosing did not further
      increase treatment efficacy in goats. It is suggested that withholding feed,
      divided-dosing or combining these methods may extend the useful life of the broad
      spectrum class of anthelmintics.

PMID- 9625465
TI  - Relationship between broiler chicken haematocrit-selected parents and their
      progeny, with regard to haematocrit, mortality from ascites and bodyweight.
AB  - A previous work of this group demonstrated that the relative haematocrit value of
      broilers is inherited and may serve as an indicator to susceptibility to the
      ascites syndrome in cold-stressed broilers. In this study, a full-pedigreed
      population was produced from male and female grandparent breeding stock that was
      selected by haematocrit and by normal selection parameters. Matings were made
      between low (L), medium (M) and high (H) haematocrit parents: L x L, M x M, and H
      x H. In their progeny, both before and after cold exposure, there was a
      statistically linear relationship between actual haematocrit and their H, M and L
      grouping (P<0.0001); heritability of the haematocrit was high (0.46-0.81). Both
      the low haematocrit parent and progeny groups showed an increased bodyweight.
      Exposure of the progeny from all the parental groups to an ascites-predisposing
      cold environment caused similar losses from ascites in the progeny of all three
      groups. Although this finding was not the same as in the previous trial where the
      H haematocrit group was associated with high ascites mortality, it is
      hypothesized that other factors, such as arterial blood saturation with oxygen,
      interacted in these birds at genetic or environmental levels.

PMID- 9625466
TI  - Pharmacokinetics and pharmacodynamics of fenleuton, a 5-lipoxygenase inhibitor,
      in ponies.
AB  - Leukotrienes, products of the 5-lipoxygenase pathway of arachidonic acid
      metabolism, possess properties consistent with their involvement in a range of
      inflammatory diseases. In this study the pharmacokinetics and pharmacodynamics of
      the selective 5-lipoxygenase inhibitor, fenleuton, have been examined in the
      horse. Orally administered fenleuton (four 5 mg kg(-1) doses, given once daily)
      was absorbed from the gastrointestinal tract, and penetrated readily into tissue
      cage exudate, the ratio of the plasma:exudate AUC0-48h being 0.90+/-0.02 (n=6).
      Ionophore-stimulated leukotriene (LT) B4 synthesis, measured ex vivo in whole
      blood as immunoreactive LTB4, was significantly (P<0.05) inhibited throughout the
      48 hour sampling period. Low levels of immunoreactive LTB4 were detected in
      transudate and these did not increase following addition of carrageenan to the
      tissue cages. Fenleuton had no significant inhibitory effect on exudate LTB4
      concentrations. A reduction in carrageenan-induced skin swelling occurred,
      although this did not achieve statistical significance. The results obtained in
      this study suggest that fenleuton could be used to examine the role of LTs in
      inflammatory diseases of the horse.

PMID- 9625467
TI  - Development of an immunomagnetic antigen capture system for detecting leptospires
      in bovine urine.
AB  - A magnetic bead antigen capture system which combined the use of two evolving
      techniques - immunomagnetic separation (IMS) and time-resolved fluoroimmunoassay
      (TR-FIA) - was developed to detect Leptospira borgpetersenii serovar hardjo in
      bovine urine. The assay utilised monoclonal antibody coated magnetic beads to
      capture leptospiral antigen which was in turn detected using another monoclonal
      antibody (Indicator) labelled with biotin. Signal was generated by the binding of
      europium labelled streptavidin to indicator antibody. The sensitivity of the
      assay was improved from 10(3) to 10(2) leptospires per ml by using an ethanol
      precipitation procedure to treat each sample. The assay detected only 31 of 56
      (55 per cent) urine specimens culture-positive for hardjo, but seven of 24 urine
      samples culture-negative for hardjo were identified as positive by the assay.
      These seven samples were from animals which were culture positive on at least one
      other occasion. These results suggest that this system should be further
      investigated as a complementary test to culture for the identification of hardjo
      carrier animals.

PMID- 9625468
TI  - Generation and functional characterisation of canine bone marrow-derived
      macrophages.
AB  - A culture of bone marrow cells from the femurs of canine pups at high
      concentrations of fetal calf serum under non-adherent conditions allowed the
      proliferation and differentiation of mononuclear phagocyte lineage cells, as
      evidenced by morphology and CD14 expression. Cells from other lineages
      progressively diminished in numbers. Cells collected between 12 and 19 days of
      culture expressed an array of macrophage activities including ingestion of
      opsonised erythrocytes, generation of superoxide, up-regulation of procoagulant
      activity and synthesis of tumour necrosis factor (TNF) upon appropriate
      stimulation. TNF production was enhanced when the cultures were simultaneously
      stimulated with canine recombinant, or supernatant-derived, interferon-gamma. In
      contrast, low levels of inducible nitric oxide (NO) synthase were expressed by
      only a minority of stimulated macrophages, and nitrite could not be detected in
      the medium. Therefore, canine macrophages generated by this novel culture system
      resemble human macrophages in their inefficient and restricted generation of NO
      upon appropriate stimulation.

PMID- 9625469
TI  - Effects of surgery on endocrine and metabolic responses to anaesthesia in horses
      and ponies.
AB  - The effects of surgery on endocrine and metabolic responses to anaesthesia were
      investigated in seven horses and eight ponies. They were anaesthetised twice and
      surgery was carried out on one occasion. Cardiorespiratory monitoring was
      performed and blood samples were taken for assay of cortisol, glucose, lactate,
      insulin, catecholamines and non-esterified fatty acids. All groups developed
      arterial hypotension which was more marked in the surgical groups where post
      operative pulse rate was also higher. Plasma cortisol concentration increased in
      all groups during anaesthesia but remained higher after surgery. Plasma lactate
      increased in all animals but was higher during surgery. Glucose, insulin and
      catecholamines did not change significantly during anaesthesia in the horses but
      NEFA decreased. Plasma glucose increased during anaesthesia in the ponies and was
      higher in the non-surgical groups. The study suggests that surgery has little
      additional effect on the stress response to halothane anaesthesia in Equidae.

PMID- 9625470
TI  - The distribution of scrapie-associated fibrils in neural and non-neural tissues
      of advanced clinical cases of natural scrapie in sheep.
AB  - The distribution of scrapie-associated fibrils (SAFs) throughout four brain
      regions, the pituitary gland, along the whole length of the spinal cord and in
      the sciatic nerve was assessed in 10 sheep terminally affected by scrapie and in
      four control sheep. Tonsils, retropharyngeal, broncho-mediastinal and mesenteric
      lymph nodes, the distal ileum, proximal colon and spleen were also examined for
      fibrils in all 14 sheep. Fibrils were detected in all four brain regions and
      throughout the length of the spinal cord in nine of the scrapie affected sheep.
      SAFs were not detectable in any of the sciatic nerve samples tested. In one of
      the 10 clinically affected sheep only minimal lesions were found by
      histopathology and fibrils were detected only from the cerebrum and one spinal
      cord region (taken at the C1 C2 vertebrae). Fibrils were not detected in the
      tonsils or retropharyngeal lymph nodes but were detected in other non-neural
      tissues of some of the scrapie-affected sheep. These tissues included pituitary
      gland, broncho-mediastinal and mesenteric portal lymph nodes, distal ileum,
      proximal colon and spleen. Fibrils could not be detected in any of the tissues
      taken from the four control sheep.

PMID- 9625471
TI  - Effects of regional analgesia and/or a non-steroidal anti-inflammatory analgesic
      on the acute cortisol response to dehorning in calves.
AB  - The effect of using a non-steroidal anti-inflammatory analgesic (ketoprofen) on
      the plasma cortisol response in calves dehorned with or without regional
      analgesia was determined. One hundred calves divided into 10 groups, four control
      and six dehorned, were used. Blood samples were taken before and after dehorning
      and plasma cortisol concentrations were measured. Dehorning caused a marked rise
      in plasma cortisol concentrations which returned to pretreatment levels after
      seven hours. The animals given ketoprofen before dehorning had a cortisol
      response similar to the dehorned animals for the first 1.3 hours after dehorning
      but then the plasma cortisol concentration returned to pretreatment levels. When
      animals were given a regional analgesic and ketoprofen the plasma cortisol
      concentrations were similar to control animals which had not been dehorned, with
      a small increase in plasma cortisol concentrations for the first hour after
      dehorning and then a rapid return to pretreatment values. This response was
      significantly lower than that seen in calves which received only regional
      analgesia. The results of this study suggest that a systemic analgesic should be
      combined with regional analgesia if the distress associated with dehorning is to
      be abolished.

PMID- 9625472
TI  - Single-injection inulin clearance--a simple method for measuring glomerular
      filtration rate in dogs.
AB  - The glomerular filtration rates (GFR) of 93 dogs of different breeds with a broad
      range of bodyweight were determined using an inulin single-injection method.
      Fifty-two dogs were used as controls, 21 dogs had suspected renal disease but
      serum creatinine in the normal range, and 20 dogs had elevated serum creatinine
      levels and a low urine specific gravity due to renal disease. Inulin was injected
      intravenously at a dosage of 100 mg kg(-1) bodyweight or 3000 mg m(-2) body
      surface. Blood samples were taken before and three, 20, 40, 80 and 120 minutes
      after injection. The total clearance was calculated from the decrease in the
      serum concentration of inulin using a two-compartment model. The range of GFR
      values was 83.5-144.3 ml min(-1) m(-2) in control dogs, 60.2-96.7 ml min(-1) m(
      2) in dogs with suspected renal disease, 50.0-76.2 ml min(-1) m(-2) in dogs with
      suspected renal disease and polyuria/polydipsia, and 16.3-63.0 ml min(-1) m(-2)
      in dogs with azotaemic renal disease. The study indicates that single-injection
      inulin clearance is a cheap and simple tool for GFR measurements in small animal
      practice.

PMID- 9625473
TI  - Close relationship between equine and human molluscum contagiosum virus
      demonstrated by in situ hybridisation.
AB  - To determine whether the virus responsible for human molluscum contagiosum (MCV)
      is the causal agent of a similar disease in horses, in situ hybridisations using
      cloned fragments of human MCV DNA labelled with digoxigenin were carried out on
      formalin-fixed biopsy sections of lesions from two horses with molluscum
      contagiosum-like skin lesions. In both instances there was evidence of specific
      hybridisation of the labelled probe to target DNA in the sections under high
      stringency conditions, identified by the development of a deep blue-purple stain
      in the cytoplasm of cells in the stratum spinosum and stratum granulosum of the
      lesions and the absence of non-specific hybridisation in adjacent non-lesional
      areas of the epidermis. These results indicate that on the basis of very close
      homology of their viral DNA sequences, the causative virus of equine molluscum
      contagiosum is either identical with, or very closely related to, its human
      equivalent.

PMID- 9625474
TI  - Cytokine expression in pulmonary and peripheral blood mononuclear cells from
      calves infected with bovine respiratory syncytial virus.
AB  - The possible involvement of cytokines in the acute viral pneumonia induced by
      respiratory syncytial virus (RSV) infection was studied in calves. The patterns
      of cytokine mRNA expression in mononuclear cells (MNC) isolated from the lung and
      peripheral blood of six gnotobiotic calves infected seven days previously with
      bovine RSV were analysed by reverse-transcription polymerase chain reaction using
      primers specific for bovine cytokines. The pattern of cytokines detected
      indicated a mixed type of response to RSV infection as mRNAs for IFN-gamma, IL-2,
      IL-4 and IL-10 were detected in pulmonary and peripheral blood MNC from calves
      with extensive pneumonic consolidation. In contrast, only mRNA for IFN-gamma was
      detected in MNC from the lungs and peripheral blood of uninfected animals. These
      data provide preliminary information on the potential range of cytokines produced
      in calves following infection with bovine RS virus.

PMID- 9625475
TI  - The influence of maternal immunity on the development of the in vitro lymphocyte
      proliferation response against pseudorabies virus in pigs.
AB  - In this study, the influence of maternal immunity against pseudorabies virus
      (PRV) on the development of a PRV-specific T-cell response in pigs was
      investigated. Pigs with or without maternal immunity were challenged by
      inoculation with wild-type PRV, or were vaccinated with 783 and subsequently
      inoculated. Peripheral blood lymphocytes, collected after vaccination and/or
      inoculation, were used for PRV-induced lymphocyte proliferation assays in vitro
      as a measure of a PRV-specific T-cell response. In unvaccinated pigs, the
      presence of maternal immunity did not inhibit the development of a T-cell
      response after inoculation with PRV. In contrast, maternal immunity did inhibit
      the development of a PRV-induced response after intramuscular vaccination.
      Moreover, vaccinated pigs without maternal immunity shed virus for a shorter
      period after inoculation than vaccinated pigs with maternal immunity. The greater
      T-cell response induced by the vaccine might have contributed to the more rapid
      clearance of PRV in these pigs.

PMID- 9625476
TI  - Chronopharmacokinetic behaviour of cyproterone acetate in rabbits.
AB  - Cyproterone acetate (CPA) is an antiandrogenic compound that shows a rhythmic
      toxicologic behaviour. The purpose of this study was to determine whether CPA
      pharmacokinetics in the rabbit were influenced by the administration time of day.
      Previously synchronised rabbits received a single intravenous dose of 4 mg kg(-1)
      of CPA at two hours after light onset (2 HALO) and 14 hours (14 HALO) after light
      onset. The drug concentration in plasma samples was determined by high
      performance liquid chromatography. The mean concentrations in plasma were
      significantly higher (P<0.05) in 2 HALO than in 14 HALO animals at five, 15 and
      30 minutes after dosing. Both plasma concentration profiles were fitted to two
      compartment open models. Mean A, Vc and Vss differed significantly between 2 and
      14 HALO dosage (P<0.005). Temporal variations in plasma protein binding, drug
      distribution and in drug elimination may play an important role in explaining
      these results.

PMID- 9625477
TI  - Sensitivity of the early luteal phase ovine cervix to prostaglandin E2 (PGE2) and
      expression of EP3 receptor mRNA.
AB  - The effects and mechanism of action of prostaglandin E2 (PGE2) on the ovine
      cervix are largely unknown in the luteal phase. In these studies we have shown
      that low levels of EP3-receptor (EP3R) mRNA are present in the ovine cervix and
      that the PGE2 induces activation of polymorphonuclear leukocytes in the ovine
      cervix on day 6 of the oestrous cycle. It is possible, therefore, that PGE2 acts
      on the ovine cervix through coupling to EP3 receptors.

PMID- 9625478
TI  - Science symposia at the British Pharmaceutical Conference.

PMID- 9625479
TI  - Why do we need new treatments for rheumatoid arthritis?
AB  - Rheumatoid arthritis is a chronic systemic autoimmune inflammatory disease
      characterized by progressive joint damage. The classical treatments of the
      disease such as myocrisin and sulphasalazine, are not always effective at
      controlling the disease. This has necessitated the development of novel agents
      for treating rheumatoid arthritis. Most of these drugs are biological in nature
      and are targeted at specific sites of the inflammatory cascade of reactions. A
      number of clinical trials have been conducted. The clinical effects that have
      been observed are transient, necessitating repeated treatments and the risk of
      vaccination effects. Many of these agents have to be administered parenterally,
      production costs are very high. Consequently, chemical entities which can be
      taken orally need to be developed. Since the immune system is very complex with
      pleiotropic cytokines and redundancy in some of the regulatory networks, it may
      therefore be necessary to use multiple agents targeted at different specific
      sites of the inflammatory cascade or that different agents could be given at
      different stages of the disease, to induce disease remission and maintain the
      response to therapy. Cytokines such as tumour necrosis factor (TNF) and
      interleukin 1 (IL-1) play important physiological roles in the host's defence
      systems against infections and malignancy. The chronic inhibition of these
      cytokines by targeted therapies may therefore lead to the development of side
      effects. Thus, carefully controlled long-term studies will be required to assess
      the safety of selective targeting of processes involved in inflammation. A more
      recent novel approach is to target hypoxic tissues with bioreductive agents.
      Thus, some of the established rheumatoid arthritis treatments could be linked to
      bioreductive agents and released in hypoxic tissues where inflammation is
      occurring. This review summarizes the important developments in the therapy of
      rheumatoid arthritis. There is no doubt that despite these developments we need
      to develop new and advanced treatment modalities for rheumatoid arthritis.

PMID- 9625480
TI  - Iontophoresis--recent developments.
AB  - This paper addresses the development and optimization of the technology of
      iontophoresis as a non-invasive approach to transdermal diagnosis and therapy.
      The rationale for this work is that the skin offers a unique and easily
      accessible body surface through which drugs can be delivered and general clinical
      monitoring information can be extracted.

PMID- 9625481
TI  - Drug-delivery products and the Zydis fast-dissolving dosage form.
AB  - Many patients find it difficult to swallow tablets and hard gelatin capsules and
      do not take their medication as prescribed. It is estimated that 50% of the
      population is affected by this problem which results in a high incidence of non
      compliance and ineffective therapy. The difficulty is experienced in particular
      by paediatric and geriatric patients, but it also applies to people who are ill
      in bed and to those active working patients who are busy or travelling,
      especially those who have no access to water. Such problems can be resolved by
      means of the Zydis dosage form which does not require water to aid swallowing.
      The Zydis fast-dissolving dosage form is a unique freeze dried medicinal tablet,
      made from well known and acceptable materials. When Zydis units are put into the
      mouth, the freeze dried structure disintegrates instantaneously releasing the
      drug which dissolves or disperses in the saliva. The saliva containing the
      dissolved or dispersed medicament is then swallowed and the drug is absorbed in
      the normal way. Some drugs are absorbed from the mouth, pharynx and oesophagus as
      the saliva passes down into the stomach. In these cases, the bioavailabilities of
      drugs from Zydis formulations are significantly greater than those observed from
      standard dosage forms. This paper deals with the formulation and process
      technology of the Zydis dosage form. The bioavailability characteristics of Zydis
      products are summarized, and in particular, the design of Zydis products for the
      enhancement of oral bioavailability and the improvement of clinical activity,
      through transmucosal delivery and pregastric absorption, is discussed.

PMID- 9625482
TI  - In-vivo monitoring of dosage forms.
AB  - The use of imaging techniques including gamma scintigraphy to follow the
      behaviour of drug formulations has revolutionized our knowledge of absorption and
      distribution in drug delivery. The development of gamma camera techniques as
      physiological tools to explore organ function became routine by the mid
      seventies. Several research groups started to explore the applications of
      technique in drug delivery. Within 5 years, the utility of the technique became
      obvious and scintigraphy is now widely accepted as an important investigation
      tool in formulation research. Gamma scintigraphy is especially useful in
      exploring sources of inter-subject variation, especially in examining food
      effects in pharmacokinetic estimations and establishing windows of absorption for
      oral delivery. As a tool to examine drug delivery to the lung and to the eye,
      scintigraphy is the method of choice. Magnetic Resonance Imaging (MRI) became
      more generally employed in medicine two decades after the gamma camera. The
      superior soft-tissue contrast and resolution compared to computed X-ray
      tomography rapidly established MRI in clinical investigation. Recent applications
      in oral drug research has allowed the pharmaceutical scientist to explore new
      facets of delivery and ultimately combine MRI and scintigraphy in human clinical
      trials.

PMID- 9625483
TI  - The design of selectively-activated anti-cancer prodrugs for use in antibody
      directed and gene-directed enzyme-prodrug therapies.
AB  - Systemic anti-proliferative agents (cytotoxins) have been the most successful
      single design concept for anti-cancer drugs. However, they have inherent
      limitations (they target dividing cells rather than cancer cells) which limit
      their clinical efficacy, especially toward the more slowly-growing solid tumours.
      New concepts are required to improve the selectivity of their killing of tumour
      cells. One possibility is the use of prodrugs which can be activated selectively
      in tumour tissue. Several potential mechanisms for this are being explored,
      including tumour hypoxia, low extracellular pH, therapeutic radiation and tumour
      specific endogenous or exogenous enzymes. In the last approach the exogenous
      enzyme can be delivered by attachment to monoclonal antibodies (ADEPT) or as DNA
      constructs containing the corresponding gene (GDEPT). A limitation of both
      approaches is that only a small proportion of the tumour cells become activation
      competent, but this can be substantially overcome by the design of appropriate
      prodrugs capable of killing activation-incompetent cells via a bystander effect.
      We have proposed a modular approach to prodrug design in which a trigger unit
      determines tumour selectivity and an effector unit achieves the desired level of
      killing of cells when the trigger is activated. For ADEPT and GDEPT prodrugs the
      primary requirement of the trigger is efficient and selective activation by the
      appropriate enzyme; the released effector must be a potent, diffusible cytotoxin
      which fully exploits the small proportion of cells capable of activating the
      prodrug. A wide variety of chemistries has been used, but many of the existing
      effectors do not have all of these properties. We report work on two types of
      cytotoxin derived from very potent anti-tumour antibiotics (enediynes and amino
      seco-cyclopropylindolines) as effectors in prodrugs for ADEPT and GDEPT
      applications.

PMID- 9625484
TI  - Genetic toxicology.
AB  - Systems for testing genetic toxicology are components of carcinogenic and genetic
      risk assessment. Present routine genotoxicity-testing is based on at least 20
      years of development during which many different test systems have been
      introduced and used. Today, it is clear that no single test is capable of
      detecting all genotoxic agents. Therefore, the usual approach is to perform a
      standard battery of in-vitro and in-vivo tests for genotoxicity. Work-groups of
      the European Union (EU), the Organization for Economic Co-operation and
      Development (OECD), and, very recently, the work-group of the International
      Conference on Harmonization of Technical Requirements for Registration of
      Pharmaceuticals for Human Use (ICH) have defined such standard battery tests.
      These and some currently used supplementary or confirmatory tests are briefly
      discussed here. Additional test systems for the assessment of genotoxic and
      carcinogenic hazard and risk are seriously needed. These tests must be more
      relevant to man than are current assays and less demanding in respect of cost,
      time and number of animals. Another aspect for reassessment derives from the
      actual situation in the pharmaceutical industry. Companies have to prepare for
      the world economy of the 21st century. Therefore, pharmaceutical research is
      speeding up tremendously by use of tools such as genomics, combinatorial
      chemistry, high throughput screening and proteomics. Toxicology and
      genotoxicology need to re-evaluate their changing environment and must find ways
      to respond to these needs. In conclusion, genetic toxicology needs to answer
      questions coming from two major directions: hazard and risk identification and
      high throughput testing.

PMID- 9625485
TI  - Compatibility of tropisetron with glass and plastics. Stability under different
      storage conditions.
AB  - The compatibility of tropisetron (pure undiluted 1 mg mL(-1) and diluted with 5%
      glucose or 0.9% NaCl (saline)) with glass, poly(vinyl chloride), polypropylene or
      polyethylene containers has been studied over a period of two weeks. The drug
      solutions were exposed to different light and temperature conditions. Tropisetron
      was assayed by high-performance liquid chromatography. The results show that
      undiluted tropisetron is stable in polypropylene syringes for two weeks under all
      the storage conditions tested (daylight at room temperature, dark at room
      temperature, refrigerator at 4 degrees C). Some variations in concentration were
      observed after dilution of tropisetron but these remained within 10% of the
      initial concentration. Tropisetron can be stored undiluted at 1 mg mL(-1) in
      polypropylene syringes, although it is preferable to perform dilutions
      extemporaneously. Tropisetron diluted with 5% glucose or saline can be kept
      equally well in glass, poly(vinyl chloride) (Travenol bags) or polyethylene
      (ecoflac) containers.

PMID- 9625486
TI  - A study on the in-vitro percutaneous absorption of propranolol from disperse
      systems.
AB  - Transdermal administration of propranolol can be used to avoid hepatic first-pass
      metabolism of the drug. The effect of polysorbate 80 concentration on the
      permeation of propranolol incorporated into micelles of polysorbate 80 in water,
      oil-in-water microemulsions of isopropyl myristate-polysorbate 80-sorbitol-water
      and oil-in-water emulsions of isopropyl myristate-polysorbate 80-sorbitan
      monooleate-water has been investigated by use of an artificial double-layer
      membrane, composed of a barrier foil and a lipid barrier, in Franz-type diffusion
      cells. Reversed-phase high-performance liquid chromatography, with celiprolol as
      internal standard, was used to determine the concentration of propranolol in the
      receptor compartment and a logarithmic equation was used to estimate the apparent
      permeability coefficient of propranolol from disperse systems. For each disperse
      system the apparent permeability coefficient of propranolol decreased with
      increasing polysorbate 80 concentration. Moreover, for a given polysorbate 80
      concentration the apparent permeability coefficient of propranolol increased when
      the disperse system was changed from emulsion to microemulsion and then to
      solubilized system, because of the increasing interfacial area of total disperse
      phase. The results show that transdermal permeation of propranolol is greater
      when it is diffused from solubilized systems rather than from microemulsions or
      emulsions.

PMID- 9625487
TI  - Kinetic interaction between fluoxetine and imipramine as a function of elevated
      serum alpha-1-acid glycoprotein levels.
AB  - The effect of elevated serum alpha-1-acid glycoprotein (AAG) levels on the
      pharmacokinetic interaction between imipramine and fluoxetine has been examined
      by utilizing a novel strain of transgenic mice which express serum AAG levels
      several times greater than normal. Before fluoxetine treatment, serum imipramine
      levels were approximately three times greater in transgenic mice than in control
      mice. Despite higher serum imipramine levels in transgenic mice, brain drug
      levels were lower than those found in control mice. Fluoxetine pre-treatment (20
      mg kg(-1) for 5 days) resulted in an increase in serum imipramine levels in both
      groups of mice and the extent of the increase was greater in transgenic mice than
      in control mice (4.5-fold increase compared with 3.1-fold). Similarly, fluoxetine
      pre-treatment resulted in an increase in brain levels of imipramine in both
      groups of mice and the extent of the increase was greater in transgenic mice than
      in control mice (3.0-fold increase compared with 2.0-fold). Similar trends were
      observed for levels of desipramine in the serum and brain. Serum imipramine and
      desipramine levels did not correlate with their respective brain levels in the
      presence of elevated serum AAG levels before and after pre-treatment. These
      findings indicate that the extent of increases in imipramine and desipramine
      serum and brain levels are greater during elevated serum AAG states than during
      normal AAG states when imipramine is co-administered with fluoxetine.

PMID- 9625488
TI  - Hepatic clearance of ONO-5046, a novel neutrophil elastase inhibitor, in rats and
      in the rat perfused liver.
AB  - The hepatic clearance of ONO-5046 (N-[2-[4-(2,2
      dimethylpropionyloxy)phenylsulphonylamino]benz oyl]aminoacetic acid), a low
      molecular-weight neutrophil elastase inhibitor, has been investigated in rats and
      in the rat perfused liver. This ester was easily hydrolysed to its inactive
      metabolite EI-601 (N-[2-[(4-hydroxyphenyl)sulphonylamino]benzoyl]aminoacetic
      acid) in liver homogenate and in erythrocytes suspension in-vitro. On the other
      hand, it was stable in biological media such as plasma and whole blood, which
      contain plasma proteins. Scatchard plot analysis of ONO-5046 binding to bovine
      serum albumin (BSA) in-vitro indicated that the association constant (K) and
      number of binding sites (n) were 6.91 x 10(4) (M(-1)) and 4.33, respectively.
      Thus, ONO-5046 (100 microM) would bind to plasma proteins to an extent >99% at
      physiological plasma-protein concentrations. The total plasma clearance of ONO
      5046 in rats was constant (approximately 9 mL min(-1) kg(-1)) under different
      steady-state plasma concentrations (5-50 microM) a value equivalent to the
      hepatic clearance. In the rat perfused liver, the hepatic extraction ratio of ONO
      5046 was significantly reduced by adding BSA to the dosing solution. Thus, the
      relatively low hepatic clearance of ONO-5046, which has an ester linkage in its
      structure and is naturally susceptible to enzymatic hydrolysis, was found to be
      because of the extremely high protein-binding of the compound.

PMID- 9625489
TI  - Effect of thioridazine or chlorpromazine on increased hepatic NAD+ level in rats
      fed clofibrate, a hypolipidaemic drug.
AB  - The effect of the phenothiazines, thioridazine and chlorpromazine, on the
      increased hepatic NAD+ level of rats fed clofibrate, a hypolipidaemic drug, has
      been investigated. Short-term (6 days) addition of phenothiazines to the diet
      negatively affected diet intake and body-weight gain, but increased liver weight
      and hepatic NAD+ levels, which was synergistic to clofibrate. The phenothiazines
      were shown to inhibit hepatic peroxisomal fatty acid oxidation in-vivo, as
      determined by the increased residual catalase activity. In hepatocytes prepared
      from clofibrate-fed rats, phenothiazines inhibited not only peroxisomal but also
      mitochondrial fatty acid oxidation to the same extent. In the hepatocytes, NAD+
      was maintained at the high level until the phenothiazine concentration was
      increased to 0.2 mM. The result suggests that the increase of hepatic NAD+ in
      rats fed clofibrate is not related to peroxisomal fatty acid oxidation.

PMID- 9625490
TI  - Contractile action of Mn2+ via Ca2+ channels activated by bay K 8644 in guinea
      pig taenia coli.
AB  - Mn2+ has been shown to inhibit K+-induced contraction of smooth-muscle, to induce
      contraction of smooth-muscle in Ca2+-free, K+ medium and to activate the
      contractile proteins of skinned fibres of smooth muscle cells. Further work has
      suggested that Mn2+ penetrates the cytoplasm through voltage-dependent Ca2+
      channels when the cell membranes of smooth muscles are depolarized with K+. We
      have investigated whether in Ca2+-free medium, Mn2+ enters the cytoplasm through
      Ca2+ channels and induces contraction of guinea-pig taenia coli in the presence
      of Bay K 8644, a dihydropyridine Ca2+-channel agonist which prolongs the open
      state of the voltage-dependent Ca2+ channels in smooth-muscle cells. In Ca2+-free
      medium the application of 5 mM Mn2+ in the presence of Bay K 8644 caused
      contraction of and concomitant increase in Mn2+ uptake in guinea-pig taenia coli
      smooth muscle. In the presence of Bay K 8644 nifedipine, a dihydropyridine Ca2+
      channel antagonist, dose-dependently inhibited both manganese uptake and the
      contraction induced by Mn2+. These results suggest that Mn2+ enters the cytoplasm
      through dihydropyridine-sensitive, voltage-dependent Ca2+ channels activated by
      Bay K 8644 and then induces contraction in taenia coli.

PMID- 9625491
TI  - Is arachis oil a solvent only, or does it also have an effect on the central
      nervous system?

PMID- 9625492
TI  - Nausea, bloating and constipation.

PMID- 9625493
TI  - Counting the cost of patients who do not attend nuclear medicine departments.
AB  - The mean rate of non-attendance at this hospital is 16%, with the Nuclear
      Medicine Department averaging 4%. Although only a small percentage, increasing
      demand for nuclear medicine studies has led to a need for greater efficiency to
      reduce financial losses. From April 1995 to March 1996, 104 patients did not
      attend over a range of 16 studies. We examined the types of study, patients and
      costs. The costs of wasted staff time, camera time and radiopharmaceutical ranged
      from pound sterling 24 (99Tc(m) thyroid) to pound sterling 470 (75Se cholesterol
      adrenal). This results in a loss equivalent to pound sterling 7258 over the year.
      There was no significant difference in non-attendance rates between different
      types of procedure, source and type of referral, or in the three age groups:
      children, working and retired population. Finally, we looked at cultural origins,
      segregating the groups into Asian and European origins based on surname. A
      significantly higher proportion of patients of Asian origin did not attend. This
      study has shown that it may be of benefit to target specific groups and tests.
      For example, at City Hospital, perhaps we should concentrate on our Asian
      community to ensure they understand fully what the study involves. It would also
      be worthwhile targeting the more expensive nuclear medicine studies.

PMID- 9625494
TI  - High-resolution inter-ictal SPET and phased-array MRI in partial epilepsy: an
      imaging comparison with video/EEG and outcome correlation.
AB  - To assess the clinical utility of high-resolution inter-ictal single photon
      emission tomography (SPET) of regional cerebral perfusion and high-resolution
      magnetic resonance imaging (MRI) of the brain with a phased-array temporal lobe
      coil, 35 patients with presumed partial epilepsy were evaluated prospectively by
      these techniques in addition to prolonged video/electroencephalographic (EEG)
      monitoring. Twenty of these patients had surgical treatment of partial epilepsy
      with outcome determinations spanning from 12 months to 3 years at follow-up.
      There were four categories of imaging findings as compared to scalp/sphenoidal
      EEG localization. Category I included 12 patients (34% of total) in whom there
      was complete imaging and EEG concordance. Category II included 4 patients (11%)
      in whom MRI and EEG were concordant but SPET was divergent or normal. Category
      III included 13 patients (37%) in whom SPET and EEG were concordant but MRI was
      divergent or normal. Category IV included 4 patients (11%) in whom neither SPET
      nor MRI was concordant with EEG. In this study, the relative sensitivities of
      SPET and MRI for localization of partial epilepsy based on prolonged
      scalp/sphenoidal video/EEG recordings were 76% and 49%, respectively. We conclude
      that these neuroimaging techniques (phased-array MRI and inter-ictal cerebral
      perfusion SPET) are complementary and useful in the pre-operative evaluation of
      patients with partial epilepsy.

PMID- 9625495
TI  - Predicting detectability in radioguided surgery: a study based on physical
      characterization of the probe and on tissue uptake ratios of 125I-, 153Sm- and
      165Er-labelled radiopharmaceuticals.
AB  - We performed measurements of the sensitivity in water of the radioguided surgery
      system, Neoprobe 1000. Point sources of 125I, 153Sm and 165Er were measured to a
      geometric accuracy of 0.1 mm. These measurements were performed with the detector
      uncollimated and with two different collimators; the results were used to
      construct three-dimensional sensitivity matrices from which isosensitivity curves
      could be derived. The matrices were used to simulate the reliability of detecting
      tumours of various sizes, at various depths, and with variable uptake ratios and
      activity levels of the three radionuclides investigated. Simulations showed
      improved tumour detection with a conical collimator, demonstrating that
      collimator design is important. To minimize the radiation dose during diagnostic
      work-up, a novel bone-seeking radiopharmaceutical, 165Er-EDTMP, was developed and
      tested. It showed rapid bone localization, especially in growth zones, and rapid
      clearance from blood and non-osseous tissues. Its biodistribution was similar to
      that of 153Sm-EDTMP. Based on these results and previous clinical data, the
      simulations predicted that lung metastases with a radius of 1 mm might be
      reliably detected with the Neoprobe 1000 system, if equipped with a suitable
      collimator.

PMID- 9625496
TI  - A simplified method for the quantitative analysis of 99Tc(m)-GSA liver
      scintigraphy using spectral analysis.
AB  - The aim of this study was to develop a simplified method for quantitative
      analysis of liver scintigraphy with 99Tc(m)-diethylenetriamine pentaacetic acid
      galactosyl-human serum albumin (GSA) using spectral analysis. Dynamic liver
      scintigraphy using GSA was performed in three normal volunteers and 19 patients
      with chronic liver disease. Dynamic data were obtained with a gamma camera for 30
      min after the injection of approximately 185 MBq GSA. The rate constant for the
      liver uptake of GSA from the blood (Ku, min(-1)), total excretion rate (Ke, min(
      1)) and non-specific volume of distribution (Vh) were obtained by spectral
      analysis. Vh was defined as the volume in the liver region of interest (ROI)
      occupied by GSA which was in equilibrium with that in the blood. It should be
      noted that Vh had no units, since the counts in both the liver and heart ROIs
      were normalized by scan length to obtain counts pixel(-1) min(-). For comparison,
      compartmental analysis was also performed. A receptor index (LHL15) was
      calculated by dividing the radioactivity of the liver ROI by that of the liver
      plus heart ROIs 15 min post-injection. The Ku values obtained by spectral
      analysis (y) agreed well with those obtained by compartmental analysis (x) (y =
      0.953x - 0.013, r = 0.992, S.E.E. = 0.016 min(-1)). The Ke and Vh values obtained
      by spectral analysis (y) correlated significantly with those obtained by
      compartmental analysis (x) (y = 1.149x - 0.016, r = 0.826, S.E.E. = 0.017 min(-1)
      for Ke; y = 1.191x + 0.044, r = 0.975, S.E.E. = 0.021 for Vh). The Ku values
      obtained by spectral analysis decreased as the severity of liver disease
      progressed, and were non-linearly related to the LHL15 values, suggesting that Ku
      is more sensitive to liver damage than LHL15, especially in the early stages of
      liver damage. These results suggest that spectral analysis applied to dynamic
      liver scintigraphy with GSA provides a simple, non-invasive and useful tool for
      the quantitative evaluation of liver function.

PMID- 9625497
TI  - Hepatobiliary scintigraphy for the diagnosis of bile leaks produced after T-tube
      removal in orthotopic liver transplantation.
AB  - Choledochocholedochostomy (CC) over a T-tube is a well-recognized technique for
      biliary reconstruction in orthotopic liver transplantation (OLT). Bile leaks
      after T-tube removal are common, having a significant morbidity. The aim of this
      study was to evaluate the utility of hepatobiliary scintigraphy (HBS) for
      diagnosing bile leaks in liver transplant patients who develop abdominal pain
      after T-tube removal. Twenty consecutive patients (14 males, 6 females; mean age
      44 years) were studied. The interval between T-tube removal and HBS ranged from 8
      to 120 h. Hepatobiliary scintigraphy was carried out after the intravenous
      injection of 185 MBq 99Tc(m)-mebrofenin. A final diagnosis of bile leak was based
      on surgical, endoscopic retrograde cholangiopancreatography (ERCP) and ultrasound
      data, and clinical outcome. There were 13 patients with and 7 without bile leaks.
      On the scintigraphic images, bile leaks were defined as activity outside the
      biliary tract which moved along the right paracolic gutter, or the progressive
      accumulation of activity related to fluid collections as seen on ultrasound. Nine
      of 12 patients needed surgical repair; the other 3 were treated with endoscopic
      sphincterotomy. One patient with a negative HBS developed an abdominal abscess
      after aspirative puncture of a biloma. In the seven patients without bile leaks,
      all scintigrams showed normal biliary transit of activity. A diagnosis of no bile
      leaks was based on clinical follow-up in five patients and by ERCP in two
      patients. Based on these results, we conclude that HBS is an effective method for
      the diagnosis of bile leaks after T-tube removal in liver transplant patients.

PMID- 9625498
TI  - Activated charcoal as a potential radioactive marker for gastrointestinal
      studies.
AB  - The scintigraphic measurement of colonic transit is currently performed using
      111In ion exchange resin pellets delivered to the colon in a capsule coated with
      a pH sensitive polymer, methacrylate, which dissolves in the distal ileum.
      However, in the USA, this requires an investigational drug permit. Our aim was to
      evaluate the in vitro binding characteristics of activated charcoal in milieus
      that mimicked gastric and small intestinal content. The in vitro incubation of
      activated charcoal was performed with Na99Tc(m)O4, 99Tc(m)-DTPA, 111InCl3, 111In
      DTPA, 201TlCl and 67Ga-citrate in the pH range 2-4 and pH 7.2 at 37 degrees C. We
      estimated the association of radiopharmaceuticals with the activated charcoal
      over a 3 h in vitro incubation. With the exception of 67Ga-citrate, the
      association of activated charcoal with the other radiopharmaceuticals was
      approximately 100% throughout the 3 h incubation. In conclusion, activated
      charcoal appears to adsorb avidly with common radioisotopes, and appears
      promising as an alternative to resin ion exchange pellets used for the
      measurement of gastrointestinal transit by scintigraphy.

PMID- 9625499
TI  - Influences on evaluability of radionuclide ventriculography in chemotherapy
      patients.
AB  - Radionuclide ventriculography (RNV) is an established method of evaluating
      cardiotoxic side-effects of chemotherapy. The image quality of RNV depends on
      labelling yields obtained after red blood cell (RBC) labelling with 99Tc(m)
      pertechnetate and has an influence on the evaluation of the left ventricular
      ejection fraction (LVEF). Several drugs and certain parameters of RBC labelling
      are known to have a detrimental effect on the labelling yield, but often the
      reason for poor image quality remains unclear. The aim of this study was to
      determine the effect of chemotherapeutic agents on LVEF evaluation. The
      chemotherapeutic medications and RNV data of 116 patients were noted. The
      patients underwent 205 RNV examinations (up to 7 RNV follow-up examinations)
      consisting of rest and stress studies. Ten patients with a poor labelling yield
      after in vivo labelling received an additional RNV study after in vitro
      labelling. The effects of commonly used anticoagulants and chemotherapeutic drugs
      on labelling yields were also investigated in experiments on in vitro RBC
      labelling. In vitro labelling had the advantage of better detection of
      pathological alterations in left ventricular motility, but often improved
      evaluability only slightly. The administration of corticosteroids showed an
      unexpected positive correlation with image quality (Spearman correlation
      coefficient: prednisone, 0.42403, P = 0.0013; prednisolone, 0.45629, P = 0.0286)
      and labelling yield (prednisolone, 0.65466, P = 0.0024), whereas idarubicin
      showed a negative correlation with image quality (-0.53364, P = 0.005). A slight
      positive correlation of prednisolone with LVEF at rest (0.45425, P = 0.0197) was
      also noted. Using our evaluation software, the manual contour method was found to
      be superior to the automatic determination of the left ventricular contour. Cycle
      ergometry alone caused a significant deterioration in image quality. The in vitro
      results suggested a negative influence of epirubicine on labelling yields at very
      high concentrations (10(-3) M). Our main result was that a clinically adequate
      study is possible in patients with moderate image quality and labelling yields.
      Furthermore, the administration of corticosteroids had a positive impact on image
      quality.

PMID- 9625500
TI  - Optimizing background correction when calculating differential renal function in
      the presence of hydroureteronephrosis using 99Tc(m)-DTPA.
AB  - We performed a prospective study to establish the optimal background correction
      algorithm for the determination of differential renal function (DRF), using
      99Tc(m)-diethylenetriamine pentaacetate (99Tc(m)-DTPA) in the presence of
      unilateral hydronephrosis, with 24 h 99Tc(m)-dimercaptosuccinic acid (99Tc(m)
      DMSA) uptake as the 'gold standard'. From September 1996 to June 1997, 12 males
      and 4 females (mean age 10 years, range 1 month to 72 years), presenting with
      unilateral hydronephrosis, were studied. All patients underwent both DTPA
      renography and quantitative DMSA scintigraphy within 24 h. In all patients, using
      a surface method, the DRF of the obstructed kidney was determined using
      infrarenal, suprarenal and perirenal background correction, time intervals of 60
      180 s (t1), 120-180 s (t2) and 80-140 s (t3), and the application or non
      application of a Rutland-Patlak correction (RPC). In the absence of RPC, for all
      three types of background correction, no difference in DTPA DRF for any of the
      three time intervals was noted; higher DTPA DRF values were found (mean +/- S.D.:
      overestimates of 7.8+/-24.4%, 6.5+/-9.5% and 3.3+/-14.9% for suprarenal,
      infrarenal and perirenal background correction, respectively). Application of RPC
      resulted in an overall decrease in both the mean and standard deviation values,
      which was most pronounced with infrarenal background correction: -0.38+/-6.5% for
      t1, 0.31+/-6.3% for t2 and -1.3 +/-6.9% for t3 (t1 vs t2, P = 0.06; t3 vs t1 or
      t2, P = 0.04). Our results suggest that infrarenal background correction using t1
      or t2 and RPC is the best algorithm for DRF estimation using 99Tc(m)-DTPA
      renography.

PMID- 9625501
TI  - 99Tc(m)-MIBI scanning of the thyroid gland in patients with markedly decreased
      pertechnetate uptake.
AB  - Diffusely reduced 99Tc(m)-pertechnetate uptake is a relatively infrequent but
      annoying finding that impairs evaluation of the thyroid gland. We studied 32
      female patients aged 19-85 years with markedly reduced pertechnetate uptake. The
      following causes of reduced pertechnetate uptake were recognized: treatment with
      iodinated pharmaceuticals (n = 15), suppression therapy with T4 (n = 11),
      subacute thyroiditis (n = 5) and massive tumour replacement (n = 1). 99Tc(m)-MIBI
      thyroid scintigraphy was performed within 24 h of the pertechnetate study. The
      results were correlated with neck ultrasound, serum TSH (n = 25) and surgical
      findings in patients who had been operated on. The technique identified the
      following conditions: normally sized thyroids (n = 4), diffuse goitres (n = 8),
      multinodular goitres (n = 17) and solitary thyroid nodules (n = 3). Moreover,
      substernal goitres were identified in nine patients. This condition was confirmed
      at surgery in seven patients. Ultrasonography was concordant in 29 of 32 patients
      in terms of thyroid size and structure, but failed to demonstrate substernal
      thyroid tissue. Our results suggest that 99Tc(m)-MIBI scintigraphy may contribute
      to the diagnosis of thyroid pathology and treatment planning in patients with
      diffusely decreased 99Tc(m)-pertechnetate uptake.

PMID- 9625502
TI  - Dopamine D2-receptor density in humans as assessed with SPET and the new high
      affinity ligand 123I-NCQ298: a pilot study.
AB  - Astra (S)-3-[123I]iodo-5,6-dimethoxyl-N-[(1-ethyl-2-pyrrolidinyl)methyl] 
      salicylamide (123I-NCQ298) is a new high-affinity D2-receptor ligand for use in
      single photon emission tomography (SPET) studies. We have studied the
      biodistribution and absorbed radiation dose of 123I-NCQ298 in humans. The mean
      effective dose for adults was 0.055 mSv MBq(-1). Brain uptake and clearance was
      measured with a head dedicated SPET camera. 123I-NCQ298 showed specific uptake in
      the basal ganglia with a low clearance rate (time constant of 9-34 h). The
      extrastriatal binding was variable (average 30%, maximum 60% of that in the basal
      ganglia at 1 h), but with a clearance rate twice that of the basal ganglia. The
      fairly high level of extrastriatal binding precluded the use of a quotient
      between the basal ganglia and cerebellum-to-frontal cortex 123I-NCQ298
      concentration as a measure for basal ganglia D2-receptor density. Chronic
      schizophrenic patients treated with conventional neuroleptics had a decreased
      affinity for 123I-NCQ298 in the basal ganglia in the range 10-60% of the median
      value for the control, untreated subjects.

PMID- 9625503
TI  - The kinetics of radiolabelled interleukin-8 in infection and sterile
      inflammation.
AB  - Radiolabelled interleukin-8 (IL-8) is a promising agent for the imaging of
      infection and inflammation. Several experiments were performed to explore further
      the imaging potential of radiolabelled IL-8. IL-8 was radioiodinated via the
      Bolton-Hunter method. Rabbits with focal infection (Escherichia coli,
      Staphylococcus aureus) or sterile inflammation (zymosan) were injected
      intravenously with 18.5 MBq (0.5 mCi) of 123I-IL-8. In separate studies, rabbits
      were injected intravenously with 111In-granulocytes with or without 125I-IL-8.
      Gamma camera images were obtained at 5 min, 1, 4 and 8 h post-injection (p.i.).
      Biodistribution was determined at 8 h p.i. In all models, the biodistribution of
      123I-IL-8 was characterized by rapid blood clearance and high uptake in infection
      and sterile inflammation. All foci could be clearly visualized within 4 h p.i. Ex
      vivo abscess-to-contralateral muscle ratios increased to 114.7+/-23.0 (E. coli),
      52.3+/-24.5 (S. aureus) and 49.8+/-8.3 (zymosan) at 8 h p.i. In the circulation,
      most 123I-IL-8 was bound to erythrocytes. The abscess uptake of 125I-IL-8 reached
      high levels despite reduced migration of granulocytes towards the site of
      infection due to the anti-inflammatory activity of intravenously injected IL-8.
      IL-8 could be injected without induction of neutropenia at a dosage of 2 ng kg(
      1). In conclusion, the characteristics of radiolabelled IL-8 for imaging of
      infection and sterile inflammation are highly encouraging and warrant further
      optimization for clinical application.

PMID- 9625504
TI  - Internalization of radiolabelled [DTPA0]octreotide and [DOTA0,Tyr3]octreotide:
      peptides for somatostatin receptor-targeted scintigraphy and radionuclide
      therapy.
AB  - We compared the internalization of [90Y-DOTA0,Tyr3]octreotide and [111In
      DOTA0,Tyr3]octreotide with that of [125I-Tyr3]octreotide and [111In
      DTPA0]octreotide in the subtype 2 somatostatin receptor (sst2)-positive rat
      pancreatic tumour cell lines CA20948 and AR42J and in the somatostatin receptor
      negative human anaplastic thyroid tumour cell line ARO. We demonstrated that
      [111In-DTPA0]octreotide, [90Y-DOTA0,Tyr3]octreotide and [111In
      DOTA0,Tyr3]octreotide are internalized by a receptor-specific, time- and
      temperature-dependent process. The amount of [90Y-DOTA0,Tyr3]octreotide
      internalized was higher than that of [111In-DOTA0,Tyr3]octreotide and [111In
      DTPA0]octreotide.

PMID- 9625505
TI  - Can chest X-rays and ventilation/perfusion scans be interpreted reliably from
      personal computer screens?
AB  - A computer-based system is routinely used for home reporting of nuclear medicine
      scans performed out of hours in our unit. To report ventilation/perfusion scans
      (V/Q) adequately, chest radiographs are also digitized and transferred to the
      home personal computer. One hundred consecutive V/Q scans and their corresponding
      chest X-rays were reported on a personal computer and on a lightbox by two
      radiologists and two nuclear physicians. This study shows that
      ventilation/perfusion scans can be reliably reported from computer screen images.
      The loss of data when chest X-rays are digitized to a 512 x 512 matrix, however,
      results in considerable misinterpretation and the digitized chest X-ray may, at
      best, be unhelpful and, at worst, result in an incorrect V/Q scan report.

PMID- 9625506
TI  - Accuracy or reproducibility?

PMID- 9625507
TI  - Prevalence of iatrogenic hyperthyroidism in a community hospital.
AB  - BACKGROUND: There is wide agreement that thyroid hormone replacement should not
      be given in doses sufficient to suppress thyroid-stimulating hormone (TSH). The
      purpose of our study was to determine the prevalence of patients currently taking
      levothyroxine who have an inappropriately suppressed TSH and are thereby at risk
      for complications of overt or subclinical hyperthyroidism. Those complications of
      particular concern are osteoporosis and cardiac toxicity, specifically atrial
      dysrhythmias and development of left ventricular hypertrophy. METHODS: The charts
      of all 1652 patients dispensed levothyroxine in 1994 from an Air Force community
      hospital were selected for review. Of these, 905 patients had an available TSH
      measurement for the same calendar year, and their status was evaluated further.
      RESULTS: Of 905 patients, 110 (12.2 percent) had TSH levels of less than 0.1
      microU/mL; 63 (7 percent) had no indication for suppression, and 21 (2.5 percent)
      were overtly thyrotoxic. The odds ratio for inappropriate suppression in women
      was 2.83 (95 percent CI 1.05 - 7.68). CONCLUSION: The frequent use of
      levothyroxine suggests that TSH suppression could represent a serious public
      health concern, particularly for postmenopausal women and patients with heart
      disease.

PMID- 9625508
TI  - Cholesterol testing and management: a national comparison of family physicians,
      general internists, and cardiologists.
AB  - BACKGROUND: We wanted to compare the frequency of cholesterol testing and
      treatment of hypercholesterolemia in patients cared for by family physicians,
      general internists, and cardiologists. METHODS: This study was a continuous cross
      sectional survey of 1991 ambulatory office visits using a national probability
      sample of US physicians' office practices (National Ambulatory Care Survey). The
      physicians surveyed self-reported their specialty as family practice, internal
      medicine, or cardiology. Records of 33,795 patient visits to 1354 physicians were
      reviewed to find out whether the physicians reported cholesterol testing,
      cholesterol counseling, and charting of patient use of lipid-lowering
      medications. The results were compared among the three specialist groups.
      RESULTS: During an annual health examination (9.77 million office visits), a
      cholesterol test was reported by 23.5 percent of family physicians, 43.5 percent
      of internists, and 13.1 percent of cardiologists (P < 0.01). For all
      hypercholesterolemic patients (23.52 million office visits), the age- and sex
      adjusted percentages of reported cholesterol-reduction counseling during office
      visits were 38.3 percent for family physicians, 42.4 percent for internists, and
      36.5 percent by cardiologists (NS), and percentages of reported lipid-lowering
      medication prescriptions were 13.4 percent for family physicians, 25.1 percent
      for internists, and 28.4 percent for cardiologists (P < 0.01). In
      hypercholesterolemic patients with coronary heart disease (3.47 million office
      visits), the age- and sex-adjusted percentages of cholesterol reduction
      counseling reported during office visits were 64.4 percent for family physicians,
      47.1 percent for internists, and 35.9 percent for cardiologists (NS) and the age-
      and sex-adjusted percentages of lipid-lowering medication prescriptions reported
      were 13.9 percent for family physicians, 62.5 percent for internists, and 34.7
      percent for cardiologists (P < 0.01). CONCLUSIONS: Recommended goals regarding
      cholesterol testing and management were not reached by any physician group.
      Internists tested for hypercholesterolemia during an annual health examination
      more frequently and had more patients using lipid-lowering medications than did
      family physicians or cardiologists. Understanding the reasons for these specialty
      differences might lead to improvement in the diagnosis and management of
      hypercholesterolemia and therefore reduction in cardiovascular disease.

PMID- 9625509
TI  - Gastrostomies in older patients: the 1990 National Hospital Discharge Survey.
AB  - BACKGROUND: Although many published case series have described patients'
      experiences after gastrostomy placement, generalizing from the results of case
      series can present problems. The purpose of this study was to examine gastrostomy
      placement among hospitalized older patients in a nationally representative
      sample. METHODS: Using the 1990 National Hospital Discharge Survey, age, sex,
      race, primary and secondary diagnoses, and mortality were described for
      hospitalized patients aged 65 years and older having gastrostomies. Age-specific
      placement rates were calculated using mid-1990 Census Bureau population
      estimates. RESULTS: In 1990 an estimated 85,400 patients aged 65 years and older
      were discharged from hospitals with gastrostomies. Frequent primary diagnoses
      included cerebrovascular disease (19 percent), pneumonia with or without
      aspiration (12 percent), neoplasm (11 percent), and fluid and electrolyte
      disorders (9 percent). The in-hospital mortality rate was 16 percent. Age
      specific rates for gastrostomy increased from 1.2 per 1000 for those aged 65 to
      74 years to 10.8 per 1000 for those aged 85 years and older. CONCLUSIONS: In 1990
      older hospitalized patients had gastrostomies with surprising frequency, and
      their in-hospital mortality rate was substantial. An estimated 1 percent of the
      US population aged 85 years and older was discharged from a hospital in 1990 with
      a gastrostomy.

PMID- 9625510
TI  - The use of alternative health care by a family practice population.
AB  - BACKGROUND: This study examined the characteristics of family practice patients
      using alternative medicine, the problems that led them to use it, and their
      satisfaction with its use. METHODS: A confidential questionnaire was mailed to
      250 randomly selected adults enrolled in a large military family practice clinic,
      with a final response rate of 71 percent. RESULTS: More than 28 percent of
      patients used some form of alternative medicine. The typical user was 30 to 49
      years old, female, white, and well educated. Common methods used were
      chiropractic (64 percent), massage therapy (36 percent), herbal therapy (32
      percent), and acupuncture (16 percent). The most common problems for which
      patients sought alternative care were back pain (56 percent), other
      musculoskeletal pain (22 percent), and stress or other psychosocial problems (20
      percent). Fewer than one half were satisfied with their alternative health care,
      although 82 percent reported at least some improvement in their conditions. Most
      (63 percent) had not told their family physician of their use of alternative
      health care. CONCLUSIONS: A substantial number of family practice patients are
      using alternative medicine. Although most derive some benefit, most are not
      satisfied with the results. Reasons for this disparity between satisfaction and
      effectiveness of alternative medicine deserve further study.

PMID- 9625511
TI  - Advances in office anesthesia.
AB  - BACKGROUND: Recent developments in anesthesia applicable to family practice
      settings are reviewed. METHODS: MEDLINE was searched using the key words "EMLA";
      "iontophoresis"; "lidocaine," "tetracaine, adrenaline, cocaine"; and "lidocaine,
      epinephrine, tetracaine." RESULTS AND CONCLUSIONS: Clinical experience has shown
      that there is a definite and evolving role for the newer methods of office
      anesthesia. Patient care can be improved by reducing the discomfort of patient
      procedures.

PMID- 9625513
TI  - Dimensions of evidence.

PMID- 9625512
TI  - Approaches to urinary incontinence in a rural population: a comparison of
      physician assistants, nurse practitioners, and family physicians.
AB  - BACKGROUND: Although urinary incontinence is a challenge and a burden to older
      patients, many clinicians fail to query older patients about incontinence
      symptoms or, even when aware of a problem, fail to diagnose the underlying cause
      or recommend treatment. We wanted to compare the approaches of physician
      assistants, nurse practitioners, and family physicians to detection, diagnosis,
      and initial management of urinary incontinence in older adults seen in rural
      primary care practices. METHODS: One male and 2 female simulated patients
      portrayed otherwise healthy patients with urinary incontinence, including urge or
      obstruction-overflow type for the man, and stress or urge type for the women. The
      3 simulated patients saw 3 physician assistants, 3 nurse practitioners, and 3
      family physicians each, for a total of 27 visits during which they posed as new
      patients seeking primary care. RESULTS: Health professionals spontaneously asked
      about incontinence in only 18 percent of visits (33 percent for physician
      assistants, 11 percent each for nurse practitioners and family physicians). When
      incontinence was discussed (spontaneously or by patient prompting), queries were
      made about potential precipitants (ie, coughing, caffeine consumption) in 63
      percent of visits. Questions about other urinary symptoms (eg, dysuria) were
      asked in 59 percent of visits. Rectal examinations were performed in 68 percent
      of the male simulated patient's visits but in none of the female simulated
      patients' visits. No pelvic examinations were performed. No attempts or
      recommendations were made to measure postvoiding residual volume. Tentative
      diagnoses were made in 48 percent of visits; some form of therapy was discussed
      in 52 percent of visits. CONCLUSIONS: Asking about incontinence was uncommon, and
      potentially important questions about precipitants and associated symptoms were
      often omitted. The providers examined areas potentially relating to incontinence
      and recommended supplementary assessments and specialized testing infrequently.
      Commonly, they made diagnoses and offered therapy at the end of an initial visit
      despite minimal history taking and examinations and lack of any additional
      assessment or testing.

PMID- 9625514
TI  - The use of corticosteroids in the management of herpes zoster.

PMID- 9625515
TI  - 2001: a health odyssey?

PMID- 9625516
TI  - Metformin-associated lactic acidosis.

PMID- 9625517
TI  - Guillain-Barre syndrome and SIADH in a patient with chronic lymphocytic leukemia.

PMID- 9625518
TI  - A gathering of eagles.

PMID- 9625519
TI  - A gastrostomy in every stomach?

PMID- 9625520
TI  - Alternative medicine and the family physician.

PMID- 9625521
TI  - Family physicians' cholesterol testing and treatment.

PMID- 9625522
TI  - Screening for dyslipidemia.

PMID- 9625523
TI  - Injury-coupled induction of endothelial eNOS and COX-2 genes: a paradigm for
      thromboresistant gene therapy.
AB  - Nitric oxide (NO) and prostacyclin (PGI2) are potent molecules produced by
      endothelial cells that act synergistically to maintain normal vascular functions.
      Recent studies indicate that key enzymes that catalyze the synthesis of these two
      molecules are induced by chemical and physical factors. Because NO and PGI2 and
      their synthetic enzymes have short half-lives, transcriptional induction by
      injurious agents, such as lysophosphatidylcholine (lysoPC), represents an
      important defense mechanism. LysoPC is capable of inducing constitutive
      endothelial NO synthase (eNOS) and cyclooxygenase-2 (COX-2), an immediate early
      gene, with distinct kinetics and possibly distinct transcriptional mechanisms.
      The importance of injury-coupled eNOS and COX overexpression in vasoprotection is
      supported by powerful effects of virus-mediated transfer of COX and eNOS genes on
      defense against thrombosis and intimal hyperplasia in angioplasty-injured carotid
      arteries in animal models.

PMID- 9625524
TI  - Anxiety-like behavior in transgenic mice with brain expression of neuropeptide Y.
AB  - Neuropeptide Y (NPY), one of the most abundant peptide transmitters in the
      mammalian brain, is assumed to play an important role in behavior and its
      disorders. To understand the long-term modulation of neuronal functions by NPY,
      we raised transgenic mice created with a novel central nervous system (CNS)
      neuron-specific expression vector of human Thy- gene fragment linked to mouse NPY
      cDNA. In situ hybridization analysis demonstrated transgene-derived NPY
      expression in neurons (e.g., in the hippocampus, cerebral cortex, and the arcuate
      nucleus of the hypothalamus) in the transgenic mice. The modest increase of NPY
      protein in the brain was demonstrated by semiquantitative immunohistochemical
      analysis and by radioreceptor assay (115% in transgenic mice compared to control
      littermates). Double-staining experiments indicated colocalization of the
      transgene-derived NPY message and NPY protein in the same neurons, such as in the
      arcuate nucleus. The transgenic mice displayed behavioral signs of anxiety and
      hypertrophy of adrenal zona fasciculata cells, but no change in food intake was
      observed. The anxiety-like behavior of transgenic mice was reversed, at least in
      part, by administration of corticotropin-releasing factor (CRF) antagonists,
      alpha-helical CRF9-41, into the third cerebral ventricle. These results suggest
      that NPY has a role in anxiety and behavioral responses to stress partly via the
      CRF neuronal system. This genetic model may provide a unique opportunity to study
      human anxiety and emotional disorders.

PMID- 9625525
TI  - Delayed wound healing and disorganized neovascularization in transgenic mice
      expressing the IP-10 chemokine.
AB  - IP-10 is a member of the alpha or cysteine-X amino acid-cysteine (CXC) chemokine
      family of chemotactic cytokines. High levels of IP-10 expression have been
      detected in a number of chronic human inflammatory conditions, including
      psoriasis, a common inflammatory disease of the skin. IP-10 has been shown to
      chemoattract activated T cells, inhibit the proliferation of endothelial cells,
      and inhibit the growth of tumors in vivo. To determine the capacity of IP-10 to
      modulate the inflammatory response in vivo, we have created transgenic mice that
      constitutively express IP-10 from keratinocytes. These mice developed normally
      and, in general, did not spontaneously recruit leukocytes into the skin or other
      organs that expressed the transgene. In addition, the transgenic mice had a
      normal cutaneous contact hypersensitivity cellular immune response. However, IP
      10 transgenic mice had an abnormal wound healing response characterized by a more
      intense inflammatory phase and a prolonged and disorganized granulation phase
      with impaired blood vessel formation. These results have demonstrated that IP-10
      can inhibit the neovascularization associated with a physiological response in
      vivo and have revealed a novel biologic activity of IP-10 as an inhibitor of
      wound healing.

PMID- 9625526
TI  - Concerted regulation of early enterocyte differentiation by insulin-like growth
      factor I, insulin, and transforming growth factor-beta1.
AB  - To clarify the roles of insulin on the proliferation and differentiation of
      intestinal epithelial cells (IECs), we examined the effect of insulin-like growth
      factor-I (IGF-I) and insulin for the growth and differentiation of IEC-6 cells, a
      crypt cell line derived from rat small intestine. IGF-I (100 nM) stimulated the
      proliferation of IEC-6 cells, and insulin (1-100 nM) antagonized the IGF-I effect
      and caused the cells' G1-arrest, resulting in differentiated characteristics of
      IECs, such as increased general protein synthesis and the formation of
      microvilli. To clarify the mechanisms of these phenomena, cell surface
      [125I]insulin binding and the content of immunoreactive insulin receptors were
      analyzed by Western blotting. Insulin receptors transiently appeared on the cell
      surface during the early G1 phase after the IGF-I stimulation. Under those
      conditions, the concomitant presence of insulin stimulated the appearance of
      active transforming growth factor-beta1 (TGF-beta1) in the media, and then TGF
      beta1 antagonized the IGF-I-induced cell proliferation. Such a TGF-beta1 effect
      was blunted by a neutralizing antibody against TGF-beta1, indicating that the
      insulin effect was in part mediated through the autocrine-paracrine secretion of
      TGF-beta1. These results suggest that the regulation of the proliferation of IECs
      are an early step in those cells' differentiation that may accompany hormonal
      changes during nutrient intake and may be caused by the sequential effects of IGF
      I, insulin, and TGF-beta1.

PMID- 9625527
TI  - Augmented expression of glomerular basement membrane specific type IV collagen
      isoforms (alpha3-alpha5) in experimental membranous nephropathy.
AB  - In human and experimental membranous nephropathy, new extracellular matrix
      accumulates between, and eventually surrounds, immune deposits on the
      subepithelial aspect of the glomerular basement membrane (GBM). To define the
      nature and source of this newly deposited matrix, we studied by in situ
      hybridization and immunohistology the production and tissue deposition of the
      recently defined basement membrane type IV collagen chain isoforms alpha3,
      alpha4, and alpha5, the mesangium-specific alpha1 and alpha2 isoforms of type IV
      collagen, and the fibrillar interstitial type I collagen during the development
      of immunological injury in passive Heymann nephritis (PHN), a rodent model of
      membranous nephropathy. Our results show that steady-state mRNA levels of alpha3
      alpha5 (IV) but not alpha1 (IV) are significantly increased in the glomeruli of
      rats with PHN at the peak of immunological injury after 14 days. Increased signal
      for alpha4 (IV) and the new appearance of alpha1 (I) could be clearly localized
      to glomerular podocytes, the target of injury in this model. In addition,
      increased levels of immunoreactive alpha3-alpha5 were visible in the peripheral
      and paramesangial GBM together with de novo deposits of type I collagen. A modest
      increase in mesangial staining for alpha1/alpha2 (IV) was present in PHN
      glomeruli. In rats depleted of complement for 5 days after PHN induction, the
      peak of alpha4 (IV) mRNA expression on day 14 was blunted. In conclusion, we have
      shown increased production of the intrinsic GBM type IV collagen isoforms alpha3
      alpha5 and ectopic production of type I collagen by injured podocytes in PHN.
      These changes may contribute to the formation of an expanded and disorganized
      GBM, as seen in experimental and human membranous nephropathy.

PMID- 9625535
TI  - Tumour cell resistance to non-MHC-restricted lymphocytes: molecular mechanisms
      and clinical implications.

PMID- 9625528
TI  - Increased susceptibility to apoptosis induced by anti-Fas antibody in a Rothmund
      Thomson syndrome lymphoblastoid cell line.
AB  - Dysregulation of apoptosis leading to reduced DNA repair capacity, increased DNA
      mutation, and chromosomal instability is one of the pathological mechanisms
      associated with aging. Rothmund-Thomson syndrome (RTS) is a human genetic disease
      characterized by several features of premature aging. Although the genetic defect
      has not been identified, defects in DNA repair capacity have been implicated in
      the pathogenesis of this disease. To determine whether dysregulation of apoptosis
      is associated with the pathogenesis of RTS symptoms, we investigated the
      sensitivity of a lymphoblastoid cell line--derived from a young (10-year-old)
      individual with RTS--to cell death induced by anti-Fas antibody (clone: CH-11).
      Cell lines derived from a normal young (14-year-old) individual and a normal aged
      (79-year-old) individual were used as controls. Treatment with CH-11 (500 ng/ml)
      resulted in significantly decreased cell viability in the RTS cell line (42.4% +/
      4.2%) and that derived from the aged individual (47.3% +/- 9.2%) as compared to
      the normal young cell line (66.9% +/- 7.0%). The concentrations of CH-11 required
      to induce 50% cell death in the RTS (IC50, 890 ng/ml) and that derived from the
      aged individual (IC50, 3640 ng/ml) were lower than that of the control young cell
      line (IC50 > 10(5) ng/ml). The lower viability was due to increased
      susceptibility to apoptosis to CH-11 in the RTS (59.0% +/- 2.0%) compared to that
      in the normal young cell line (40.9% +/- 0.9%) as shown by 7-amino-actinomycin D
      (7-AAD) staining (p < .005). Treatment of the RTS cell line with acetyl-Asp-Glu
      Val-Asp-aldehyde (Ac-DEVD-CHO), a specific inhibitor of caspase-3, significantly
      increased the cell viability after CH-11 treatment (75.9% +/- 2.2%). Taken
      together, these results provide the first evidence to show that RTS
      lymphoblastoid has an increased sensitivity to cell death mediated by Fas and
      that inhibition of caspase-3 activity may be a potential target in reversing the
      sensitivity of RTS cells to Fas-mediated apoptosis in vitro.

PMID- 9625536
TI  - Antitumor vaccination effect of dendritic cells can be augmented by locally
      utilizing Th1-type cytokines from OK432-reactive CD4+ T cells.
AB  - In order to enhance the antitumor vaccination effect of dendritic cells (DC)
      pulsed with class I tumor peptide, we tried to utilize the local cytokine help of
      CD4+ T cells reactive to a streptococcal preparation OK432. DC were prepared from
      murine bone marrow cells by culture with both granulocyte/macrophage-colony
      stimulating factor and interleukin(IL)-4. The peritumoral injections of OK432
      induced OK432-reactive CD4+ T cells in the draining lymph nodes, and their in
      vitro production of interferon gamma was thus significantly enhanced by
      restimulation with OK432-pulsed DC. In addition, anti-P815 mastocytoma cytotoxic
      T lymphocytes were generated from the in vivo OK432-treated P815-draining lymph
      node cells only when the lymph node cells were restimulated in vitro with the DC
      pulsed with both P1A peptide and OK432. Moreover, the peritumoral injections of
      OK432 and the subsequent vaccination of the DC, pulsed with both OK432 and P1A
      peptide, significantly suppressed the growth of s.c. inoculated P815.
      Interestingly, a significant level of IL-12 was detected in the coculture
      supernatant of both OK432-pulsed DC and OK432-reactive CD4+ T cells.
      Collectively, our results suggest that the antitumor vaccination effect of DC
      pulsed with class I tumor peptide could thus be effectively augmented by locally
      utilizing the Th1-type cytokines from OK432-reactive CD4+ T cells.

PMID- 9625537
TI  - Suppression of tumorigenicity and metastasis in murine UV-2237 fibrosarcoma cells
      by infection with a retroviral vector harboring the interferon-beta gene.
AB  - In this study, we endeavored to determine the effectiveness of interferon beta
      (IFNbeta) gene therapy against highly metastatic murine UV-2237m fibrosarcoma
      cells. UV-2237m cells were engineered to produce murine IFNbeta constitutively
      following infection by a retroviral vector harboring the murine IFNbeta gene.
      Parental (UV-2237m-P), control-vector-transduced (UV-2237m-Neo), and IFNbeta
      transduced (UV-2237m-IFNbeta) cells were injected subcutaneously (s.c.) or
      intravenously (i.v.) into syngeneic mice. Parental and control-transduced cells
      produced rapidly growing tumors, whereas IFNbeta-transduced cells did not. The
      tumorigenicity of IFNbeta-sensitive or -resistant parental cells was
      significantly suppressed when they were injected s.c. together with IFNbeta
      transduced cells. The IFNbeta-transduced cells did not inhibit growth of parental
      cells injected s.c. at a distant site. UV-2237m-IFNbeta cells produced s.c.
      tumors in nude, SCID/Beige, and natural killer(NK)-cell-compromised syngeneic
      mice. The IFNbeta-transduced cells were more sensitive to in vitro splenic cell
      mediated lysis than were the parental or control-transduced cells. Pretreatment
      of C3H/HeN mice with the NK-cell-selective antiserum (anti-asialoGM1) partially
      abrogated the cytotoxic activity of the cells. Cytotoxic activity was not
      observed in mixed culture of UV-2237m-IFNbeta cells and splenic cells from
      SCID/Beige mice. Significant cytotoxicity against UV-2237m-IFNbeta cells was
      mediated by macrophages activated by either IFNgamma, lipopolysaccharide, or a
      combination of both. Our data led us to conclude that the constitutive expression
      of IFNbeta can suppress tumorigenicity and metastasis of UV-2237m cells, which is
      due, in part, to activation of host effector cells.

PMID- 9625538
TI  - Selective tumoricidal effect of soluble proteoglucan extracted from the
      basidiomycete, Agaricus blazei Murill, mediated via natural killer cell
      activation and apoptosis.
AB  - We have isolated a novel type of natural tumoricidal product from the
      basidiomycete strain, Agaricus blazei Murill. Using the double-grafted tumor
      system in Balb/c mice, treatment of the primary tumor with an acid-treated
      fraction (ATF) obtained from the fruit bodies resulted in infiltration of the
      distant tumor by natural killer (NK) cells with marked tumoricidal activity. As
      shown by electrophoresis and DNA fragmentation assay, the ATF also directly
      inhibited tumor cell growth in vitro by inducing apoptotic processing; this
      apoptotic effect was also demonstrated by increased expression of the Apo2.7
      antigen on the mitochondrial membranes of tumor cells, as shown by flow
      cytometric analysis. The ATF had no effect on normal mouse splenic or interleukin
      2-treated splenic mononuclear cells, indicating that it is selectively cytotoxic
      for the tumor cells. Cell-cycle analysis demonstrated that ATF induced the loss
      of S phase in MethA tumor cells, but did not affect normal splenic mononuclear
      cells, which were mainly in the G0G1 phase. Various chromatofocussing
      purification steps and NMR analysis showed the tumoricidal activity to be chiefly
      present in fractions containing (1-->4)-alpha-D-glucan and (1-->6)-beta-D-glucan,
      present in a ratio of approximately 1:2 in the ATF (molecular mass 170 kDa),
      while the final purified fraction, HM3-G (molecular mass 380 kDa), with the
      highest tumoricidal activity, consisted of more than 90% glucose, the main
      component being (1-->4)-alpha-D-glucan with (1-->6)-beta branching, in the ratio
      of approximately 4:1.

PMID- 9625539
TI  - Nitric oxide inhibits proliferation but increases life-span of T lymphocytes in
      tumour-bearing rats.
AB  - Nitric oxide (NO) has been shown to inhibit the proliferation of lymphocytes.
      However, in tumour-bearing rats treated with the immunomodulator OM 163, the
      regressing nodules were heavily infiltrated by T lymphocytes, although they
      contained high levels of NO. We show here that NO, while inhibiting the
      proliferation of lymphocytes, increased their life-span, pointing to the
      ambivalence of this molecule in the course of tumour growth and regression.

PMID- 9625540
TI  - Anti-(epidermal growth factor) receptor monoclonal antibodies for the induction
      of antibody-dependent cell-mediated cytotoxicity against squamous cell carcinoma
      lines of the head and neck.
AB  - Squamous cell carcinomas of the head and neck (SCCHN) frequently display high
      levels of the epidermal growth factor receptor (EGFR). Since EGFR is expressed on
      the cell surface it may form a suitable target for anticancer therapy with anti
      receptor monoclonal antibodies (mAb). Besides the interference with
      receptor/ligand interactions, binding of mAb to EGFR leads to immunoglobulin
      coated tumour cells that may induce or enhance non-specific immune effector
      mechanisms like antibody-dependent cell-mediated cytotoxicity (ADCC). In
      established cell lines of SCCHN (UM-SCC 11B, 14C, 22B, and 8029 NA) we
      investigated the antitumour activity of allogeneic peripheral blood mononuclear
      cells (PBMC) in combination with rat (ICR 62), mouse (EMD 55900), and humanized
      (EMD 72000) anti-EGFR mAb. In addition, autologous PBMC were available for tumour
      line UD-SCC 4. The EGFR protein content of the tumour cell lines ranged between
      170 fmol/mg protein and 8100 fmol/mg protein, and MCF-7 cells served as receptor
      negative controls. PBMC activity against SCCHN targets was determined in 96-well
      microtitre-plate monolayer cultures by the colorimetric 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide assay after coincubation for 4 h, 24 h and 72
      h at effector target ratios of 1:1, 5:1, 10:1 and 20:1. PBMC subpopulations were
      obtained by macrophage depletion (plastic adherence) or natural killer (NK) cell
      enrichment (magnetic bead negative selection). Prolonged time of exposure and
      increased effector:target ratios revealed marked antitumour activity of PBMC
      alone. This non-specific immune destruction was enhanced considerably by
      humanized and rat, but not mouse anti-EGFR mAb. Increased EGFR protein in tumour
      cells partly correlated with an intensification of ADCC but was accompanied by
      decreased primary PBMC cytotoxicity. The utilization of PBMC subpopulations
      suggested a mainly NK-cell-mediated ADCC, which appeared to benefit directly or
      indirectly, e.g. via the secretion of cytokines, from other PBMC components. In
      conclusion, humanized (EMD 72000) and rat (ICR 62) anti-EGFR mAb were able to
      generate strong antitumour ADCC in target monolayers of SCCHN.

PMID- 9625541
TI  - Comparison of the effect of latanoprost 0.005% and timolol 0.5% on the calculated
      ocular perfusion pressure in patients with normal-tension glaucoma.
AB  - PURPOSE: To compare the calculated mean ocular perfusion pressure at the end of 3
      weeks' treatment with latanoprost 0.005% once daily or timolol 0.5% twice daily
      in normal-tension glaucoma patients. METHODS: In a three-center, double-masked,
      randomized, crossover study, 36 patients were allocated to two treatment groups;
      one received 3 weeks each of placebo, latanoprost, placebo, and timolol, whereas
      the other group had placebo, timolol, placebo, and latanoprost. Intraocular
      pressure and resting systemic blood pressure were measured at 9 AM, 12 noon, and
      4 PM. Ocular perfusion pressure was calculated for each time period as well as
      the mean of three values (daytime average). Systemic blood pressure and heart
      rate were also recorded at 30-minute intervals during the last 24 hours of each
      treatment period. RESULTS: The average daytime mean ocular perfusion pressure
      (mean +/- SEM) following latanoprost treatment was 53.2 +/- 1.4 mm Hg, an
      increase of 8% from the latanoprost run-in period, compared with 50.9 +/- 1.1 mm
      Hg following timolol treatment, an increase of 2% from the timolol run-in period
      (P < .05, ANOVA). Timolol reduced the blood pressure. The difference in mean
      daytime and nighttime systolic blood pressure measurements as well as nighttime
      diastolic blood pressure was about 5 mm Hg between the latanoprost and timolol
      treatments. The daytime and nighttime heart rates were also slower during the
      timolol treatment. CONCLUSION: Because ocular perfusion pressure may be important
      in some glaucomatous patients, latanoprost appears to affect ocular perfusion
      pressure more favorably than timolol does in patients with normal-tension
      glaucoma.

PMID- 9625542
TI  - The ability of scanning laser ophthalmoscopy to identify various glaucomatous
      optic disk appearances.
AB  - PURPOSE: To compare four distinct glaucomatous disk appearances using scanning
      laser ophthalmoscopy and determine the ability of a previously described
      discriminant analysis to detect glaucomatous damage for each group. METHODS: Two
      thousand three hundred eighty-eight stereoscopic optic disk photographs of 2,388
      subjects with glaucoma or suspicion of glaucoma were reviewed to select four pure
      glaucomatous optic disk types. Twenty-three topographic, volumetric, and
      morphometric scanning laser ophthalmoscopic variables from one optic disk of each
      selected subject were compared. Differences between the groups were evaluated
      using an analysis of variance and the Pearson chi-square test. RESULTS: Forty
      four focal ischemic disks, 38 myopic glaucomatous disks, 30 senile sclerotic
      disks, and 28 disks characterized by generalized cup enlargement were studied.
      Significant intergroup differences were found for the majority of the evaluated
      optic disk variables. The accuracy with which the discriminant analysis model was
      able to detect disks with glaucomatous visual field damage was 93.2% for focal
      ischemic disks, 81.6% for myopic disks, 66.7% for senile sclerotic disks, and
      78.6% for disks with generalized cup enlargement. CONCLUSIONS: By comparing mean
      values for certain optic disk variables, scanning laser ophthalmoscopic optic
      disk assessment can distinguish groups of disks with specific appearances.
      However, the ability of presently available software to detect glaucomatous
      damage varied considerably with disk appearance. Expert clinical optic disk
      evaluation remains an important part of the assessment of patients suspected of
      having glaucoma, although refinement of computerized scanning laser
      ophthalmoscopic disk assessment may eventually make this easier.

PMID- 9625543
TI  - Topless optic disks in children of mothers with type I diabetes mellitus.
AB  - PURPOSE: To determine the prevalence of and risk factors for superior segmental
      optic nerve hypoplasia in offspring of mothers with type I diabetes mellitus.
      METHODS: Thirty-four subjects aged between 4 and 37 years, the children of 23
      mothers who had type I diabetes mellitus at the time of pregnancy, aged between 4
      and 37 years, were recruited from one institution and prospectively examined in
      search of an optic disk-related anomaly. RESULTS: Of the 34 subjects, three
      females (8.8%) showed classic ophthalmoscopic and perimetric features of superior
      segmental optic nerve hypoplasia, bilateral in two patients and unilateral in
      one. Pregnancies leading to affected children showed a tendency to be shorter,
      birth weight to be lower, and control of maternal diabetes mellitus to be poorer
      compared with pregnancies resulting in unaffected children. No variable unique to
      the affected subjects as opposed to the unaffected majority could be identified.
      CONCLUSIONS: We found a superior segmental optic nerve hypoplasia, described as a
      "topless disk," in three of 34 subjects (8.8%) at risk for this condition.
      Topless disk thus seems to be more common than was previously thought, possibly
      having been missed because of its subtle signs and only mild impairment of visual
      performance in affected individuals. Female sex, short gestation time, low birth
      weight, and poor maternal diabetes control may represent additional risk factors
      for the development of a topless disk. Its pathogenesis remains obscure, but the
      responsible pathogenic event may occur in the perinatal period.

PMID- 9625544
TI  - Prospective randomized comparison of phacoemulsification cataract surgery with a
      3.2-mm vs a 5.5-mm sutureless incision.
AB  - PURPOSE: To report sutureless cataract surgery by phacoemulsification with a 3.2
      mm surgical incision compared with a 5.5-mm surgical incision. METHOD: In a
      prospective, randomized, masked clinical trial of phacoemulsification cataract
      surgery, 55 eyes (55 patients) had a 3.2-mm incision and 56 eyes (56 patients)
      had a 5.5-mm incision. All incisions were in the superior vertical meridian,
      commenced 1.5 mm posterior to the limbus, and extended into the cornea for a
      total length of 2.5 to 3.0 mm. In a masked fashion, astigmatism was monitored by
      keratometry, and logMAR visual acuity was determined both with and without best
      correction throughout a mean follow-up of 33.9 months. RESULTS: Statistically
      significant differences were seen in favor of the 3.2-mm incision group at the
      final examination for astigmatism (Cravy analysis) and uncorrected visual acuity
      (-0.18 vs -0.88 diopter, P < .001; logMAR, 0.14 vs 0.26, P = .04). CONCLUSIONS:
      Over the long term, phacoemulsification with a 3.2-mm incision is associated with
      significantly less astigmatic shift and better uncorrected visual acuity than is
      phacoemulsification with a 5.5-mm incision. A small incision with a foldable
      intraocular lens has long-term benefits.

PMID- 9625545
TI  - Posterior capsular plaque: a common feature of cataract surgery in the developing
      world.
AB  - PURPOSE: To study the histopathologic findings of posterior capsular plaque, a
      lesion that is discovered frequently in eyes undergoing cataract surgery in the
      developing world. METHODS: Two hundred human crystalline lenses removed from 200
      eyes of 200 patients who underwent intracapsular cataract extraction at
      Sagarmatha Choudhary Eye Hospital in Nepal were analyzed histopathologically.
      RESULTS: Forty-nine lenses (24.5%) had a posterior capsular plaque. We confirm
      that the posterior plaques are composed of collagen that stains positively for
      Masson trichrome stain and that forms after pseudofibrous metaplasia of lens
      cells along the posterior capsule. The plaques form in a fashion analogous to a
      healing process. CONCLUSIONS: We postulate that posterior capsular plaques result
      from posterior migration of epithelium and pseudofibrous metaplasia of lens
      epithelium. Most of the posterior capsular plaques are minute and not likely to
      affect vision. However, a small percentage of plaques are thicker and are likely
      to impair vision after extracapsular cataract surgery.

PMID- 9625546
TI  - Translocation of the retina for management of subfoveal choroidal
      neovascularization I: experimental studies in the rabbit eye.
AB  - PURPOSE: To report a surgical method for retinal translocation as a potential
      treatment for eyes with subfoveal choroidal neovascularization. METHODS: Thirty
      right eyes of 30 pigmented rabbits were used for this study. The first 15 were
      used to develop the technique. The complete surgical technique for retinal
      translocation was performed in the last consecutive 15 rabbits. Intravitreal
      injection of sulfur hexafluoride was performed to compress and liquefy the
      vitreous. Two weeks later, we used transscleral subretinal hydrodissection to
      create a retinal detachment. A scleral resection was then performed near the
      equator in the superotemporal quadrant. Fundus photographs were taken to record
      the retinal status before, immediately after, and 1, 3, and 7 days after surgery.
      Electroretinography was performed in three rabbits 3, 7, and 14 days after
      retinal translocation. Histologic studies were performed in one rabbit 7 days
      after retinal translocation. RESULTS: Our results are based on experiments
      performed in the last consecutive 15 rabbits. One day after surgery, retinal
      reattachment was observed in 14 of the 15 animals. The remaining animal developed
      endophthalmitis. A predictable retinal translocation of about 1,000 microm was
      achieved. Retinal tears were noted on the retinal folds in four cases after 1
      week. Electroretinographic studies showed transient reduction in retinal
      function. Mild morphologic damage to the outer retinal layers was seen
      histologically. Retinal detachment or proliferative vitreoretinopathy did not
      develop in any rabbit in the 14 days of follow-up. CONCLUSIONS: Limited retinal
      translocation with repositioning of the central retina was accomplished in
      rabbits.

PMID- 9625547
TI  - Translocation of the retina for management of subfoveal choroidal
      neovascularization II: a preliminary report in humans.
AB  - PURPOSE: To report a surgical method for translocation of the foveal retina in
      eyes with subfoveal choroidal neovascularization. METHODS: In three eyes of three
      patients, a crescent-shaped, partial-thickness scleral resection was performed
      near the equator at either the superotemporal or the inferotemporal quadrant. A
      near-total retinal detachment was created; then the edges of the resected sclera
      were sutured, causing shortening of the sclera with subsequent reattachment of
      the retina, resulting in translocation of the fovea to an area overlying
      nonfoveal retinal pigment epithelium and choroid. RESULTS: In three eyes of three
      patients, the fovea was surgically translocated to overlie retinal pigment
      epithelium that preoperatively was not underlying the fovea. In two patients,
      laser photocoagulation was applied to the choroidal neovascularization that,
      after translocation of the fovea, was no longer subfoveal, so that the
      photocoagulation was not associated with immediate visual loss. After a follow-up
      of 4 to 6 months, the visual acuity had improved in all patients (from 20/126
      preoperatively to 20/70 in one patient, from 20/200 preoperatively to 20/70 in
      the second, and from 20/160 to 20/30 in the third). The patients noted distortion
      or tilting of the images, which improved over time. CONCLUSIONS: Limited foveal
      translocation may offer a therapeutic modality to preserve or improve vision in
      cases of subfoveal choroidal neovascularization. Additional follow-up is needed
      to assess the impact of potential complications associated with the surgical
      procedure, such as retinal detachment, proliferative vitreoretinopathy, and
      cataract, as well as the possibility of recurrent choroidal neovascularization.

PMID- 9625548
TI  - Visual function after foveal translocation with scleral shortening in patients
      with myopic neovascular maculopathy.
AB  - PURPOSE: To document the visual outcome after successful foveal translocation
      with intentional retinal detachment and scleral shortening for the treatment of
      myopic neovascular maculopathy. METHODS: Two severely myopic patients with
      subfoveal neovascular membranes underwent surgical translocation of the fovea to
      an area of healthy retinal pigment epithelium by means of scleral shortening and
      intentional retinal detachment. In the postoperative period, monocular and
      binocular visual function were studied. RESULTS: In one patient, best-corrected
      visual acuity improved from 20/150 to 20/20 postoperatively. In the second
      patient, acuity initially improved from 20/70 to 20/30. In both patients, the
      fixation point shifted from the site of the neovascular membrane. Oblique
      astigmatism developed and was managed with hard contact lenses. Diplopia and
      subjective torsion occurred transiently. Micropsia occurred in one patient.
      Peripheral fusion assessed by Worth four-dot testing after resolution of diplopia
      disclosed suppression in the nondominant eye in both cases. CONCLUSIONS: Foveal
      translocation with intentional retinal detachment and scleral shortening was
      useful in improving visual acuity in two patients with myopic neovascular
      maculopathy. Diplopia and aniseikonia occurred but resolved over time as
      suppression developed. This technique is promising for patients with myopic
      neovascular maculopathy.

PMID- 9625549
TI  - Scanning laser ophthalmoscope fundus perimetry after surgery for choroidal
      neovascularization.
AB  - PURPOSE: Submacular surgery is under investigation for the treatment of subfoveal
      choroidal neovascularization secondary to age-related macular degeneration,
      ocular histoplasmosis syndrome, and other causes. The aims of this study were to
      determine whether the macular area from which choroidal neovascularization was
      removed surgically remained functional and whether there was any qualitative
      difference between eyes with different disease conditions or between eyes of
      younger and older patients. METHODS: Our study included 19 patients (19 eyes)
      with choroidal neovascularization, seven cases caused by age-related macular
      degeneration and 12 caused by ocular histoplasmosis syndrome, pathologic myopia,
      or idiopathic causes. All tests were performed at least 6 months after surgical
      removal of choroidal neovascularization. All patients underwent fundus perimetry
      with the scanning laser ophthalmoscope for evaluation of dense and relative
      scotomas and fixation site. RESULTS: After submacular surgery in 19 patients, 10
      patients (one with age-related macular degeneration and nine with pathologic
      myopia, ocular histoplasmosis syndrome, or an idiopathic cause of choroidal
      neovascularization) fixated within an area that ophthalmoscopically and
      angiographically was an area of retinal pigment epithelial disturbance occupied
      by choroidal neovascularization preoperatively. Of 12 patients without age
      related macular degeneration, seven of eight patients younger than 50 years of
      age compared with two of four patients 50 years or older fixated within the area
      of retinal pigment epithelial disturbance. CONCLUSIONS: Our data suggest that in
      patients without age-related macular degeneration who undergo submacular surgery,
      the surgically disturbed area previously occupied by choroidal neovascularization
      can remain functional postoperatively. Furthermore, occasionally a patient with
      age-related macular degeneration undergoing submacular surgery still can fixate
      in the area from which the choroidal neovascularization was removed.

PMID- 9625550
TI  - Serous detachment of the ciliary body in Harada disease.
AB  - PURPOSE: To evaluate the involvement of the anterior ocular segment in Harada
      disease. METHODS: In a prospective study, ultrasound biomicroscopy was performed
      in 18 consecutive eyes of nine patients with Harada disease in its acute phase
      before and after onset of systemic corticosteroid therapy. Examination was
      repeated every 3 days until the resolution of serous retinal detachment. RESULTS:
      Serous detachment of the ciliary body was present in 11 (61%) of 18 eyes before
      treatment. The circumference of the ciliary body was detached in 10 of the 11
      eyes. The height of ciliary detachment ranged from 20% to 250% of the scleral
      thickness. Ciliary detachment was more prominent in eyes with more extensive
      retinal detachment. There was no relation between the frequency of ciliary
      detachment and the severity of iritis. On day 3 of treatment, ciliary detachment
      had disappeared in seven eyes. In the other four eyes, it diminished in height to
      less than 10% of scleral thickness. Retinal detachment disappeared on days 6
      through 17 (mean, day 11) of treatment. Two eyes of one patient showed very
      shallow anterior chambers. These eyes showed high ciliary detachment at 250% of
      scleral thickness. In another patient, both eyes developed -5.0 diopters of
      transient myopia. CONCLUSION: Ciliary detachment was a frequent finding in the
      acute stage of Harada disease. Its resolution was more prompt than that of serous
      retinal detachment after treatment. Ciliary detachment may be related to the
      development of a shallow anterior chamber.

PMID- 9625551
TI  - Dexamethasone concentration in vitreous and serum after oral administration.
AB  - PURPOSE: To determine the dexamethasone concentration in vitreous and serum of
      patients after oral administration of dexamethasone and to compare the results
      with the concentrations in vitreous and serum found in a previous study with
      peribulbar injection of 5 mg dexamethasone disodiumphosphate. METHODS: In a
      prospective study, 54 patients who were scheduled for vitrectomy received 7.5 mg
      dexamethasone orally at varied time intervals before surgery. A vitreous sample
      was taken from each patient and serum samples were collected at multiple time
      points from 32 out of 54 patients. Dexamethasone concentrations were measured by
      radioimmunoassay. RESULTS: Dexamethasone concentrations in serum ranged from 2.5
      to 98.1 ng/ml (median, 61.6 ng/ml) between 1 and 3 hours after oral
      administration of 7.5 mg dexamethasone. Serum concentrations after peribulbar
      injection of 5 mg dexamethasone disodiumphosphate (containing 3.75 mg
      dexamethasone) were lower by a factor of 1.5. Concentrations in vitreous ranged
      from 1.7 to 23.4 ng/ml (median, 5.2 ng/ml) between 4 and 10 hours after oral
      administration. After peribulbar injection of 5 mg dexamethasone
      disodiumphosphate, the intravitreal concentrations were 3.9 times higher.
      CONCLUSIONS: An oral dose of 7.5 mg dexamethasone resulted in an intravitreal
      corticosteroid concentration with an anti-inflammatory potency that is clearly
      above physiological level. This concentration, however, is several times lower
      than is the intravitreal concentration after a peribulbar injection of 5 mg
      dexamethasone disodiumphosphate, although the two routes of administration
      resulted in nearly equal dexamethasone concentrations in serum. The higher
      intravitreal concentration after peribulbar injection is probably caused by
      diffusion from the serum and additional transscleral diffusion.

PMID- 9625552
TI  - Ophthalmic and genetic screening in pedigrees with familial adenomatous
      polyposis.
AB  - PURPOSE: To study the possible association between ophthalmic findings, genetic
      status, and clinical course of the disease in Austrian pedigrees with familial
      adenomatous polyposis (FAP). METHODS: Thirty-nine members of 16 consecutive FAP
      families with 20 affected patients and 19 relatives with a 50% a priori risk to
      develop the disease were examined ophthalmologically. The intestinal status of
      all persons was established by colonoscopy. Direct or indirect molecular genetic
      analysis, or both, was possible in eight of the 16 FAP families. RESULTS:
      Congenital hypertrophy of the retinal pigment epithelium (CHRPE) was discovered
      in 15 (75%) of the 20 persons affected by familial adenomatous polyposis. Five
      (25%) of the patients with an established FAP were CHRPE-negative. Four of the 19
      at-risk individuals were CHRPE-positive. According to DNA analysis, five of the
      19 at-risk relatives had a high risk to develop a manifest disease. The
      ophthalmoscopic tests were in complete agreement with the molecular risk
      estimation. Furthermore, the combined results of endoscopy and ophthalmoscopy
      suggested a relationship between a positive CHRPE status and the severity of FAP.
      CONCLUSIONS: Ophthalmic examinations facilitate predictive diagnosis in FAP
      patients and first-degree relatives, permitting a noninvasive, highly reliable
      risk assessment. When present, CHRPE lesions are a reliable clinical marker for
      FAP in CHRPE-positive families. In CHRPE negative families, negative ophthalmic
      examinations are of no predictive value. The CHRPE status can add information
      about the location of the genetic mutation. The combination of an ophthalmic
      examination with DNA analysis and endoscopy improves the risk assessment of FAP
      carriers.

PMID- 9625553
TI  - Polymerase chain reaction-based risk assessment for Wilms tumor in sporadic
      aniridia.
AB  - PURPOSE: Sporadic cases of aniridia have a 30% risk for the development of Wilms
      tumor. Current guidelines for sporadic aniridia recommend screening by renal
      ultrasonography for the presence of tumors every 6 months until age 5 years.
      Deletions of chromosome 11p13 that affect both PAX6 (aniridia) and WT1 (Wilms
      tumor) loci are the basis for the association of these two uncommon disorders. We
      sought to develop a rapid polymerase chain reaction-based test that could rule
      out a chromosome 11p13 deletion covering the PAX6-WT1 region in sporadic
      aniridia. METHODS: Five patients with sporadic aniridia were recruited.
      Polymerase chain reaction-based genotyping was carried out for six highly
      informative marker loci across the PAX6-WT1 region to determine whether these
      patients had one or two haplotypes. The results were compared with those obtained
      from two cell lines with known deletions in the PAX6-WT1 region. RESULTS: All
      five patients were heterozygous at least at one of the four marker loci in the
      PAX6-WT1 region, indicating that there were no cases of gross chromosomal
      deletion. The cell lines showed hemizygosity in the four marker loci within the
      PAX6-WT1 region and in one of the two flanking marker loci. CONCLUSIONS: We have
      developed a rapid DNA test with an estimated sensitivity of 94.0% to 99.2%, using
      standard DNA diagnostic techniques and equipment, to rule out chromosomal
      deletion in sporadic aniridia. Patients in whom a chromosome 11p13 deletion has
      been ruled out do not require repeated renal imaging to screen for Wilms tumor.

PMID- 9625554
TI  - Argon laser therapy of benign tumors of the eyelid.
AB  - PURPOSE: To report the therapy of benign eyelid tumors with an argon laser as an
      alternative to surgery. METHODS: Forty-one patients with 47 benign tumors of the
      eyelid were included in this study. In all patients, the eyelid tumor was
      eliminated by argon laser. In 24 cases the lower eyelid and in 23 cases the upper
      eyelid was involved, including the lid margin in 17 cases. Laser spot size ranged
      from 150 to 500 microm. Argon laser power density varied between 4.1 and 61.1
      W/mm2. Spots were counted between 40 and 1204. Twenty-seven of 41 patients
      treated were followed up; the mean follow-up period was 5.8 months (range, 3 to
      24 months). Postoperatively, histologic confirmation was obtained in 42 cases of
      the 47 treated tumors. RESULTS: All patients were satisfied regarding the laser
      therapy and the cosmetic result. Remarkably, the wounds were dry after argon
      laser therapy. No infections of the wounds occurred; wounds were epithelialized
      after 2 to 3 weeks by a normal-appearing epithelium. The area of argon laser
      treatment was less pigmented than the surrounding skin and showed no obvious
      remarkable notches. As a complication, one patient developed a viral
      conjunctivitis. No relapses occurred during follow-up. CONCLUSIONS: Argon laser
      therapy of benign eyelid tumors may result in very satisfactory wound healing.
      Taking the short follow-up and the limited number of cases into account, it seems
      to be a useful alternative to traditional surgery, especially for tumors
      positioned close to the lacrimal papillae.

PMID- 9625555
TI  - Macular translocation.

PMID- 9625556
TI  - The effect of aqueous humor suppressants on intravitreal gas bubble duration in
      rabbits.
AB  - PURPOSE: To evaluate the effect of topical aqueous humor suppressants on the
      absorption of intravitreal perfluorocarbon gases. METHODS: Sulfur hexafluoride or
      perfluoropropane was injected intravitreally in five rabbits. Time to gas
      disappearance was measured in eyes treated with topical aqueous humor
      suppressants and in those not treated. RESULTS: The mean time (+/- SD) to
      disappearance of 0.4 cc of sulfur hexafluoride was 5.6 +/- 0.9 days, which was
      prolonged by 43% to 8.0 +/- 0.7 days with topical aqueous humor suppressants (P =
      .009). The mean time (+/- SD) to disappearance of 0.2 cc of perfluoropropane was
      18.4 +/- 1.9 days, which was prolonged by 55% to 28.6 +/- 2.7 days with topical
      aqueous humor suppressants (P = .009). CONCLUSION: Aqueous suppressants prolong
      sulfur hexafluoride and perfluoropropane intravitreal gas bubble duration in
      rabbits.

PMID- 9625557
TI  - Vitrectomy in patients with decreased visual acuity secondary to asteroid
      hyalosis.
AB  - PURPOSE: To evaluate the role of vitrectomy in patients with decreased visual
      acuity solely attributable to asteroid hyalosis. METHOD: We retrospectively
      reviewed the records of patients with asteroid hyalosis and identified those who
      underwent vitrectomy for symptomatic asteroid hyalosis alone. RESULTS: After
      vitrectomy, nine of 10 eyes (10 patients) had at least 1 line of improvement in
      nonstandardized best-corrected visual acuity. In one eye, vision was unchanged
      postoperatively. The average gain was 3.44 lines. CONCLUSIONS: A small percentage
      of patients with asteroid hyalosis have decreased visual acuity caused solely or
      primarily by the asteroid hyalosis. Vitrectomy in these patients may alleviate
      symptoms and improve visual acuity.

PMID- 9625558
TI  - The topographic distribution of the first sites of diabetic retinal
      neovascularization.
AB  - PURPOSE: To examine the topographic distribution of the origin of diabetic
      retinal neovascularization. METHODS: The eyes of 3,121 patients with background
      diabetic retinopathy were investigated. These patients were volunteers in
      systemic medical therapy experiments. Color stereo photographs were obtained
      annually. The first retinal neovascularization sites were identified and the
      distances from the optic nerve measured. RESULTS: In 1 year, neovascularization
      originated in 282 eyes. The superotemporal quadrant, at 6 mm from the optic disk,
      was the most frequent initial site. CONCLUSIONS: The first retinal
      neovascularization sites cluster around specific anatomic foci. This information
      should influence retinopathy monitoring protocols.

PMID- 9625559
TI  - Internal carotid artery dissection causing a branch retinal artery occlusion in a
      young adult.
AB  - PURPOSE: To report a 34-year-old healthy man with an internal carotid artery
      dissection who presented with an ipsilateral branch retinal artery occlusion.
      METHOD: Case report. RESULTS: Ophthalmic examination of a young adult presenting
      with transient monocular visual loss and a superior nasal field defect disclosed
      a left inferior branch retinal artery occlusion. After fluorescein angiography,
      the patient had a vasovagal response, and his condition worsened to a left
      central retinal artery occlusion. Neurologic evaluation followed by carotid
      angiography disclosed a left internal carotid artery dissection with total
      occlusion of the internal carotid artery. CONCLUSION: The differential diagnosis
      of retinal arterial occlusion in a young healthy adult without any notable ocular
      or medical history, including trauma, should include spontaneous internal carotid
      artery dissection.

PMID- 9625560
TI  - Association of xerophthalmia, flecked retina, and pseudotumor cerebri caused by
      hypovitaminosis A.
AB  - PURPOSE: To report an unusual case of hypovitaminosis A with bilateral
      papilledema and flecked retina that regressed after restoration of vitamin A
      deficiency. METHOD: Case report. A 27-year-old woman had undergone a
      biliopancreatic bypass for obesity in 1990. In 1995, she presented with bilateral
      xerophthalmia, bilateral papilledema, and bilateral flecked retina. RESULTS:
      Laboratory tests demonstrated low serum levels of vitamin A (0.8 micromol/l) and
      vitamin E (8.54 micromol/l). Xerophthalmia, papilledema, and flecked retina
      disappeared after restoration of normal vitamin A blood levels. CONCLUSION:
      Hypovitaminosis A after biliopancreatic bypass for obesity may be associated with
      xerophthalmia, pseudotumor cerebri, and flecked retina.

PMID- 9625561
TI  - Examination of patients with cystoid macular edema using a scanning laser
      ophthalmoscope with infrared light.
AB  - PURPOSE: To report a noninvasive method for evaluating eyes with cystoid macular
      edema. METHODS: We obtained infrared images of cystoid macular edema in eight
      eyes of eight patients using a scanning laser ophthalmoscope with the dark-field
      mode of a 780-nm diode laser. Differences between infrared images and fluorescein
      angiograms in the imaging of cystoid changes were examined. RESULTS: With the
      scanning laser ophthalmoscope, we observed cystoid macular changes as images that
      resembled three-dimensional pictures in the dark-field mode with infrared light.
      Cystoid changes observed by this method generally agreed with changes observed by
      fluorescein angiography. CONCLUSIONS: Scanning laser ophthalmoscopy with infrared
      light in a dark-field mode is noninvasive, and the results in eyes with cystoid
      macular edema generally agreed with results obtained by fluorescein angiography.
      This method is useful for examining eyes with cystoid macular edema.

PMID- 9625562
TI  - Scanning laser ophthalmoscopic findings in a patient with acute zonal occult
      outer retinopathy.
AB  - PURPOSE: To examine a 33-year-old woman who had an enlarged scotoma in her right
      eye and who was diagnosed with acute zonal occult outer retinopathy. METHODS: We
      performed a full ophthalmologic examination and scanning laser ophthalmoscopy.
      RESULT: With a 514-nm wavelength laser, scanning laser ophthalmoscopy
      demonstrated abnormal lesions bilaterally. No abnormalities were detected with a
      630-nm wavelength laser. CONCLUSION: Scanning laser ophthalmoscopy can
      demonstrate retinal damage caused by acute zonal occult outer retinopathy, which
      is useful in differential diagnosis.

PMID- 9625563
TI  - Eyelid laceration in a neonate by fetal monitoring spiral electrode.
AB  - PURPOSE: To report an unusual case of birth injury caused by an internal fetal
      monitoring spiral electrode. METHOD: Case report. RESULTS: A neonate with eyelid
      lacerations was examined within the first hour of life after a fetal scalp
      electrode was inadvertently affixed to the left upper eyelid during labor. The
      superficial lacerations healed without sequelae, and there was no globe injury.
      CONCLUSIONS: Ocular adnexal birth injury by a fetal monitoring scalp electrode
      has been reported rarely. Because fetal brow malpresentation is uncommon, the
      occurrence of this injury is unusual. Although alarming, the periorbital edema
      associated with this malpresentation probably protects the eyelid from
      perforation and the globe from injury.

PMID- 9625564
TI  - T-cell malignant lymphoma with conjunctival involvement.
AB  - PURPOSE: To report a rare case of T-cell malignant lymphoma involving the
      conjunctiva. METHODS: A 63-year-old woman had rapid onset of bilateral perilimbal
      congestion and chemosis. Perilimbal thickening with corneal infiltration
      developed 20 days later. Computed tomography incidentally disclosed a right
      maxillary sinus mass. Biopsy specimens from the maxillary sinus mass and the left
      limbus were subjected to histopathologic examination and immunohistochemical
      study. RESULTS: T-cell malignant lymphoma of diffuse large cell type, stage IV,
      was diagnosed. The patient was treated with combination chemotherapy plus 13-cis
      retinoic acid and remained in remission 1 1/2 years after diagnosis. CONCLUSION:
      Conjunctival involvement with T-cell lymphoma may present as episcleritis and
      chemosis.

PMID- 9625565
TI  - Topical diclofenac sodium in the management of anesthetic abuse keratopathy.
AB  - PURPOSE: To report a case of anesthetic abuse keratopathy and to suggest the use
      of topical diclofenac sodium in the management of this disorder. METHOD:
      Narcotics and topical diclofenac were used to control pain in a patient who
      developed a corneal ulcer after abusing topical anesthetics. RESULT: After the
      institution of topical diclofenac, the patient reported substantial improvement
      in comfort and less reliance on narcotic agents for analgesia. CONCLUSION: We
      found topical diclofenac to be useful in controlling pain in this patient with
      anesthetic abuse keratopathy.

PMID- 9625566
TI  - Acanthamoeba keratitis with symbiosis of Hartmannella ameba.
AB  - PURPOSE: To report a case of severe amebic keratitis in which both Hartmannella
      and Acanthamoeba were isolated simultaneously from the same lesion. METHOD: Case
      report. The deep corneal lesion was scraped for cytopathology and isolation of
      the pathogens. We tested the in vitro sensitivities of the pathogens to several
      drugs. RESULTS: Cultures of the corneal scrapings and of the solution in the
      patient's contact lens storage case were positive for Acanthamoeba E9 cysts and
      trophozoites. Hartmannella ameba coexisted with Acanthamoeba in the cornea. When
      tested in vitro, Acanthamoeba trophozoites were sensitive to both miconazole
      nitrate and natamycin, while cysts were sensitive only to natamycin. However, the
      patient did not respond to these antiamebic drugs. CONCLUSIONS: This case
      suggests that Acanthamoeba is not the only origin of amebic keratitis.
      Hartmannella may also cause severe drug-resistant keratitis.

PMID- 9625567
TI  - Infectious crystalline keratopathy caused by Candida guilliermondii.
AB  - PURPOSE: To describe the manifestations of infectious crystalline keratopathy
      caused by Candida guilliermondii in a corneal transplant performed for
      pseudophakic bullous keratopathy. METHOD: Case report. RESULTS: Candida
      guilliermondii was identified as the causative organism of an indolent infectious
      crystalline keratopathy. Incisional lamellar biopsy provided diagnostic culture
      and histopathologic results. Histopathology showed aggregates of yeast elements
      between corneal stromal lamellae, without inflammation. The infection progressed
      despite a 6-week course of topical amphotericin B and an additional 6-week course
      of topical and oral fluconazole. Repeat penetrating keratoplasty resulted in
      clear graft, with no recurrent infection. CONCLUSIONS: Fungal keratopathy should
      be included in the differential diagnosis of infectious crystalline keratopathy.
      Numerous Candida species have been isolated in addition to the most common
      causative bacterial organism, Streptococcus viridans. Candida guilliermondii is
      yet one more causative agent of infectious crystalline keratopathy. Candida
      guilliermondii, a rare human pathogen, was resistant to medical therapy in this
      case.

PMID- 9625568
TI  - Very high frequency ultrasound analysis of a new phakic posterior chamber
      intraocular lens in situ.
AB  - PURPOSE: To use very high frequency ultrasound scanning for in situ analysis of a
      new phakic posterior chamber intraocular lens (No-Touch; International Visions
      Inc, Cincinnati, Ohio). METHODS: In this pilot study, very high frequency
      ultrasound (50 MHz) wide-angle (15 mm) full anterior segment scans were obtained
      in two patients who had undergone phakic posterior chamber intraocular lens
      implantation into legally blind eyes with normal anterior segment anatomy.
      RESULTS: Very high frequency ultrasound B-scan images delineated the phakic
      posterior chamber intraocular lens within the posterior chamber. The relations to
      the sulci were clearly imaged. Anatomic relations of the phakic posterior chamber
      intraocular lens optic and haptics were visualized in both static (light/dark)
      and kinetic (distance/accommodative) states. CONCLUSION: Very high frequency
      ultrasound wide-angle scanning provides a unique tool to noninvasively evaluate
      the eye preoperatively and the static and kinetic relations of this new
      refractive device within the posterior chamber.

PMID- 9625569
TI  - Iris metastasis from endometrial carcinoma.
AB  - PURPOSE: To report a case of metastasis to the iris from endometrial carcinoma.
      METHOD: Case report. A 67-year-old woman with a history of endometrial carcinoma
      and local recurrence after surgery presented 11 months later with two yellow-pink
      nodules on the iris of the right eye. RESULTS: Systemic medical evaluation
      demonstrated no other metastases. The iris tumors were removed surgically, and
      histology demonstrated adenocarcinoma consistent with endometrial carcinoma.
      CONCLUSIONS: Endometrial carcinoma can metastasize to the iris. This possibility
      should be considered because the frequency of endometrial carcinoma is
      increasing.

PMID- 9625570
TI  - Vascular endothelial growth factor and severity of nonproliferative diabetic
      retinopathy mediate retinal hemodynamics in vivo: a potential role for vascular
      endothelial growth factor in the progression of nonproliferative diabetic
      retinopathy.

PMID- 9625571
TI  - Assessment of sexually transmitted diseases services in city and county jails-
      United States, 1997.
AB  - Approximately 15 million arrests were made in the United States in 1995, and the
      number of persons incarcerated has increased 72% since 1990. At any given time,
      approximately 567,000 persons are incarcerated in local jails (i.e., county or
      city correctional facilities housing persons serving short-term sentences or
      awaiting trial). The prevalence of sexually transmitted diseases (STDs) among
      incarcerated women is high: syphilis, 35%; chlamydia, 27%; and gonorrhea, 8%.
      However, limited information is available about the extent of STD diagnosis and
      treatment services in correctional facilities. During July-August 1997, CDC
      conducted a survey of STD testing and treatment policies and practices in jails.
      This report summarizes the results of the survey, which indicates that most
      facilities treat for STDs based on symptoms or by arrestee request and do not
      routinely screen asymptomatic persons.

PMID- 9625572
TI  - Syphilis screening among women arrestees at the Cook County Jail--Chicago, 1996.
AB  - Cook County (Chicago) Department of Corrections (i.e., Cook County Jail [CCJ]) is
      one of the largest jail systems in the United States, with a daily census of
      approximately 10,000 arrestees. CCJ contracts with Cermak Health Services (CHS)
      to provide medical services, including routine syphilis screening, to arrestees
      at CCJ. On January 6, 1996, the Chicago Department of Public Health (CDPH)
      STD/HIV Program, in collaboration with the CCJ, CHS, and CDC, implemented the
      Rapid Plasma Reagin (Stat RPR) Project at CCJ to improve syphilis identification
      and treatment rates among women. This report describes the project and provides
      data from the first year of operation. The findings indicate that Stat RPR yields
      a higher treatment rate for women arrestees than routine syphilis testing.

PMID- 9625573
TI  - Assessing adolescent pregnancy--Maine, 1980-1996.
AB  - Despite prevention efforts at the state and federal levels, adolescent pregnancy
      rates in the United States are among the highest in developed countries. The 1996
      Personal Responsibility and Work Opportunity Reconciliation Act mandates a
      national strategy to prevent pregnancy among teenagers and requires that states
      establish goals to reduce the incidence of "out-of-wedlock" pregnancies,
      particularly among teenagers. Adolescent pregnancy and birth rates are declining
      across the nation; in particular, the rates have decreased substantially in
      Maine. This report summarizes an evaluation of pregnancy rates for persons aged
      15-19 years in Maine and an assessment of clinical and behavioral factors that
      may have contributed to decreasing rates during 1980-1996 by the Maine Department
      of Human Services, Bureau of Health (MBH); the Family Planning Association of
      Maine (FPA); and CDC. From 1980 through 1996, pregnancy rates in Maine among
      females aged 15-19 years decreased from 67.9 to 45.6 pregnancies per 1000. A
      decrease in oral contraceptive (OC) use and increases in the use of condoms and
      long-acting methods were significantly correlated with the decrease in adolescent
      pregnancy rates from 1984 to 1996.

PMID- 9625574
TI  - Novel cytomorphology of the giant proerythroblasts of parvovirus B19 infection.
AB  - The morphology of the giant proerythroblasts (GPE) in air-dried and Wright-Giemsa
      stained smears of bone marrow in 16 patients with pure red cell aplasia (PRCA)
      caused by parvovirus B19 infection is described. B19 infection was diagnosed by
      the presence of the virus or viral DNA and/or IgM antibodies. Twelve patients had
      chronic hemolytic anemia and aplastic crisis and 4 patients had AIDS with chronic
      PRCA. In patients with chronic hemolytic anemia and aplastic crisis, GPE were not
      detectable in bone marrow biopsies that showed any degree of recovery of
      erythropoiesis. The GPE morphology was quite variable. The early (basophilic) GPE
      measured 25 to 35 microm in diameter, had a narrow rim of intensely blue and
      often vacuolated cytoplasm with pseudopodia, round nuclei with compact
      uncondensed chromatin, and an indistinct and inclusion-like purple-colored
      tinctorial change. The "intermediate" and "late" GPE measured 25 to 45 microm in
      diameter and showed cytoplasmic swelling, gradual loss of cytoplasmic basophilia,
      and fraying of the cytoplasm with focal rupture; the nuclei showed an increase in
      volume, a highly uncondensed and coarse sieve-like chromatin, and 1 to 3
      prominent, pale to moderate purple inclusion-like nucleoli or inclusions. Bare
      nuclei similar in size and chromatin pattern to those of the GPE were present in
      proximity to the GPE and may have arisen from the GPE by dissolution of the
      cytoplasm. The glassy intranuclear inclusions with central clearing, the so
      called lantern cells described in formalin-fixed tissues of patients with B19
      infection, were absent in all cases. These findings suggest that direct toxic
      cell injury rather than apoptosis may be involved in the pathogenesis of
      erythroid aplasia in B19 infection.

PMID- 9625575
TI  - Splenic abscess and sickle cell disease.
AB  - This is a report of our experience with 10 cases of splenic abscess in patients
      with sickle cell disease (SCD). All presented with fever and abdominal pain and
      were found to have a tender enlarged spleen. Two were found to have a ruptured
      spleen and five of them were septicemic on presentation. Although both ultrasound
      and CT-scan of the abdomen were of diagnostic value, we found CT-scan more
      accurate and reliable in the diagnosis of splenic abscess. Ultrasound and/or CT
      scan should be used routinely in the evaluation of SCD patients who present with
      fever and abdominal pain, especially if they have a tender enlarged spleen.
      Diagnostic aspiration under CT-scan or ultrasound guidance should be used in
      doubtful cases to differentiate between splenic abscess and a large splenic
      infarct. All our patients were managed by peri operative antibiotics and
      splenectomy with no mortality. Salmonella was the commonest causative organism.
      Although CT-guided aspiration of splenic abscess is being advocated recently, we
      feel splenectomy should be the treatment of choice in patients with SCD as there
      is no point in preserving a non-functioning spleen that is present in the
      majority of patients. CT-guided aspiration may be employed as a temporary measure
      for those patients who are at high surgical risk with unilocular abscess.

PMID- 9625576
TI  - Fludarabine, cytarabine, and G-CSF (FLAG) for the treatment of poor risk acute
      myeloid leukemia.
AB  - Thirty-eight patients with primary resistant or relapsing acute myeloid leukemia
      (AML) were treated with fludarabine, cytarabine and granulocyte colony
      stimulating factor (FLAG). Median age was 41 (range 11-70). Sixteen patients had
      AML that was primary resistant to induction treatment, while 22 were relapsed, 11
      after autologous bone marrow transplant (AuBMT), 8 less than 6 months from
      complete remission (CR) achievement, and 3 were second relapse from chemotherapy
      alone. Overall, 21 of 38 patients (55%) obtained CR. Age, sex, length of CR, and
      interval between autoBMT and FLAG administration did not significantly influence
      the CR rate. On the contrary, a normal karyotype at diagnosis was significantly
      related to a better outcome. There were 4 induction deaths (10%), due to fungal
      infection in 2 patients and hemorrhagic complications in the remaining two. All
      patients experienced profound cytopenia. Median time to neutrophil (>500/microl)
      recovery was 21 days, while a platelet count >20,000/microl was reached after 23
      days. The median period of hospitalization was 31 days. The nonhematological
      toxicity was mild, mainly consisting of mucositis. There were 17 documented
      infections and 17 episodes of fever of unknown origin. Following CR achievement,
      6 patients received autoBMT, 3 alloBMT, 2 high-dose arabinosil-cytosine, and 2
      are on a waiting list for transplantation procedure. We conclude that FLAG is an
      effective and well-tolerated regimen for refractory or recurrent AML, mainly
      useful for patients to be admitted to bone marrow transplantation.

PMID- 9625577
TI  - Efficacy and safety of continuous infusion of Mononine during five surgical
      procedures in three hemophilic patients.
AB  - We report here five surgeries successfully performed with a continuous infusion
      of Mononine (Armour Pharmaceutical Company, Kankakee, IL) in three hemophilic B
      patients. Before surgery the patients received a bolus dose of 40 to 100 U/kg
      according to the type of surgery. This injection was followed by a continuous
      infusion of Mononine, with an infusion rate of 3.5-7 U/kg/hr in order to maintain
      a factor IX level between 50 and 100% during the whole surgery and the following
      6 days. The infusion rate was further adjusted according to the type of surgery
      until hospital discharge. This method appears to be safe and efficient, since no
      abnormal bleeding occurred during surgery and none of the patients presented any
      thrombotic complication. However, this alternative to intermittent administration
      of factor IX should be standardized and precisely evaluated, regarding the level
      and the amount of factor IX required, and the cost of the infused material. In
      our hands, this cost was decreased by 30-40% compared to previous therapeutic
      schedules at our institution.

PMID- 9625578
TI  - Oral L-glutamine therapy for sickle cell anemia: I. Subjective clinical
      improvement and favorable change in red cell NAD redox potential.
AB  - Previously, we demonstrated that there is an increased utilization of glutamine
      by intact sickle red blood cells (RBC) in conjunction with nicotinamide adenine
      dinucleotide (NAD) metabolism in vitro. In this report, we describe the in vivo
      effect of L-glutamine supplementation on total NAD, nicotinamide adenine
      dinucleotide reduced (NADH), and NAD redox potential of sickle RBC. Seven adult
      sickle cell anemia patients participated in this study. The exclusion criteria
      were pregnancy, previous or current use of hydroxyurea, and transfusion within 3
      months of initiation of the study. After proper consent, L-glutamine was started
      at a dose of 30 g/day administered orally. Fasting blood samples were drawn at
      baseline and after 4 weeks of therapy by routine phlebotomy for evaluation of RBC
      total NAD and NADH levels. We found significant changes in both the NADH level
      and NAD redox potential (ratio of NADH to NAD+ + NADH). NAD redox potential
      increased from 47.2 +/- 3.7% to 62.1 +/- 11.8% (P < 0.01). The NADH level
      increased from 47.5 +/- 6.3 to 72.1 +/- 15.1 nmol/ml RBC (P < 0.01). The total
      NAD level demonstrated an upward trend (from 101.2 +/- 16 to 116.4 +/- 14.7
      nmol/ml RBC) but this was not statistically significant. Our data show that oral
      L-glutamine can significantly increase the NAD redox potential and NADH level in
      sickle RBC. These changes may decrease oxidative susceptibility of sickle RBC and
      result in clinical benefit.

PMID- 9625579
TI  - Hepatitis C virus infection in acquired aplastic anemia.
AB  - Hepatitis-associated aplastic anemia (HAAA) is an uncommon disorder that usually
      is not due to hepatitis A or B virus infection. Hepatitis C virus (HCV)
      seropositivity is infrequently observed in aplastic anemia (AA) patients who have
      not been extensively transfused. However, HCV seropositivity may not be detected
      until several weeks or months after viral infection and AA patients may exhibit
      defective humoral immunity. Therefore, we evaluated sera from AA patients for the
      presence of HCV viremia using a reverse transcriptase polymerase chain reaction
      (RT-PCR) based assay and several serologic assays for HCV antibodies. Serum
      samples from 90 AA patients who presented to the UCLA Medical Center between
      March 1984 and February 1990 were analyzed. Overall, 17 patients were found to
      have HCV viremia by RT-PCR assay, of whom 14 had a positive second-generation HCV
      enzyme immunoassay (EIA-2) and only 6 were EIA-1 reactive. The frequency of HCV
      viremia increased with the duration of time between diagnosis and sample
      procurement, and the number of blood products transfused prior to sampling (P =
      0.026). No patient who received fewer than 20 U of blood products or who was
      sampled less than 20 days after diagnosis had a positive HCV RT-PCR result. Of
      four patients with hepatitis-associated AA (HAAA), one who was sampled 23 days
      after diagnosis had hepatitis C viremia and a reactive EIA-2 assay. Therefore,
      the high frequency of HCV viremia in this patient population is most likely due
      to transfusion with contaminated blood products prior to the introduction of
      routine blood donor screening for HCV.

PMID- 9625580
TI  - Coincidental occurrence of pernicious anemia and mycosis fungoides in two elderly
      males.
AB  - We experienced two rare cases of pernicious anemia that presented in the course
      of mycosis fungoides in elderly males. Pernicious anemia has recently been
      reported to be caused by autoimmune gastritis that produces autoantibodies to
      gastric parietal cells and intrinsic factor. Immunological abnormalities in
      mycosis fungoides are reported to induce autoimmune diseases (i.e., autoimmune
      hemolytic anemia, anti-phospholipid antibody syndrome, arthritis, myasthenia
      gravis, necrotizing vasculitis, and vitiligo); the pernicious anemia in our two
      patients may have been closely related to the mycosis fungoides.

PMID- 9625581
TI  - Clinically silent primary adrenal lymphoma: a case report and review of the
      literature.
AB  - Primary adrenal lymphoma (PAL) is extremely uncommon. We describe a case of
      clinically silent non-Hodgkin's B-cell lymphoma of diffuse large cell type with
      exclusive left adrenal localization. The tumor was discovered by computed
      tomography (CT) as a 2.5-cm dense mass and diagnosed at autopsy. Literature
      concerning this unusual neoplasm is reviewed. During the early stage,
      particularly when the lesion is small, PAL is likely to be missed. This unusual
      entity should be included in the differential diagnosis of adrenal masses so that
      early diagnosis may be made and intervention might dramatically affect the
      clinical outcome.

PMID- 9625582
TI  - Clinical and cytogenetic remission induced by interferon-alpha in a patient with
      chronic eosinophilic leukemia associated with a unique t(3;9;5) translocation.
AB  - A patient with chronic eosinophilic leukemia and a unique complex chromosomal
      translocation 46,XY,t(3;9;5)(q25;q34;q33) who had elevated blood interleukin-5 is
      reported. Complete cytogenetic remission was induced by interferon-alpha after
      treatment failure with corticosteroids and cytotoxic drugs. Severe
      cardiopulmonary symptoms due to hypereosinophilia and thromboembolic complication
      improved dramatically in the first 6 months of interferon therapy. Since it is
      known that the gene encoding for interleukin-5 resides on the long arm of
      chromosome 5, it may be possible that the chromosomal translocation in our
      patient resulted in overproduction of this cytokine, and our findings may be
      helpful for understanding the pathogenesis of this disorder.

PMID- 9625583
TI  - Acute renal failure precipitated by non-steroidal anti-inflammatory drugs
      (NSAIDs) in multiple myeloma.

PMID- 9625584
TI  - Cloning and sequencing of an alternative splicing-derived cDNA variant of the GM
      CSF receptor alpha subunit, which encodes a truncated protein.
AB  - GM-CSF interacts with the low affinity GM-CSF receptor alpha-subunit, which leads
      to high affinity association with the alpha-subunit/common beta-subunit complex
      and transduction of intracellular signals leading to proliferation,
      differentiation, and/or activation of hemopoietic cells, predominantly in the
      neutrophil and monocyte/macrophage lineages. Several alternative splicing-derived
      variants of the GM-CSF receptor alpha-subunit have been described previously by
      this and other laboratories. A newly discovered alternative-splicing derived
      variant was isolated from the peripheral blood mononuclear cells of a patient
      with juvenile myelomonocytic leukemia. This variant lacks 397 base pairs
      corresponding to exons 8-11 of the wild type GM-CSF receptor alpha-subunit cDNA
      and potentially encodes a 233 amino acid protein lacking a membrane-anchoring
      domain and creating the fourth known potential soluble isoform of the alpha
      subunit of the GM-CSF receptor.

PMID- 9625585
TI  - Thrombotic thrombocytopenic purpura associated with HIV and visceral Kaposi's
      sarcoma treated with plasmapheresis and chemotherapy.
AB  - We present a case of a patient who is HIV positive and developed both thrombotic
      thrombocytopenia purpura and visceral Kaposi's sarcoma (KS) with hemorrhage. This
      case presents a difficult management problem in that the patient's bleeding
      originated from KS lesions and did not quickly abate with plasmapheresis therapy
      despite both clinical and laboratory improvement after 2-4 days. Chemotherapy was
      initiated on day 13 and the patient's condition improved markedly afterward. We
      believe the addition of chemotherapy to plasmapheresis hastened the improvement
      of our patient's thrombotic thrombocytopenic purpura (TTP) and KS-related
      bleeding. Therefore, under similar conditions, we recommend combining
      plasmapheresis and chemotherapy at the onset of therapy.

PMID- 9625586
TI  - Factor V Leiden mutation does not account for central venous catheter-related
      thrombosis.
AB  - Indwelling central venous access devices are frequently associated with catheter
      related thrombosis. The factor V Leiden gene mutation decreases the sensitivity
      of factor V to the anticoagulant activity of activated protein C, and has been
      shown to be the most common inherited defect associated with a hypercoagulable
      state. In this study, we sought to determine whether an increased prevalence of
      the factor V gene mutation could be identified in individuals with malignancies
      who had catheter-related thrombosis. Twenty-seven patients who had catheter
      related thrombosis were identified and two (7%) tested positive for the
      heterozygous presence of the factor V gene mutation. Since the vast majority of
      patients with venous access devices who developed catheter-related thrombosis did
      not have the factor V gene mutation, pre-catheter placement testing for this
      mutation would have limited clinical utility.

PMID- 9625587
TI  - Unexplained bleeding, arterial stenosis, alopecia, and a splenic catastrophe.

PMID- 9625589
TI  - Intraabdominal immunoglobulin light chain amyloid tumor encompassing a vascular
      malformation.

PMID- 9625588
TI  - A relapse of acute promyelocytic leukemia after long-term remission of 9.5 years
      with negative PML-RARalpha mRNA.

PMID- 9625590
TI  - Appearance of an inhibitor to factor VIII in a hemophilia A patient with HIV
      infection treated with combination anti-retroviral therapy.

PMID- 9625591
TI  - A 13C nuclear magnetic resonance study of free fatty acid incorporation in
      acylated lipids in differentiating preadipocytes.
AB  - To understand the role of free fatty acid (FFA) incorporation in the accumulation
      of lipids in the adipocyte and ultimately in the development of obesity, 13C
      nuclear magnetic resonance was used to study lipid metabolism in differentiating
      preadipocytes. The incorporation of 13C=O-labeled FFA into cellular lipids in
      primary cultured rat preadipocytes and 3T3L1 preadipocytes at different stages of
      differentiation was monitored by the 13C carbonyl chemical shift. Significant
      incorporation of palmitic acid into phosphatidylcholine in both the alpha and
      beta acyl chain positions was found in cells at early stages of differentiation.
      At later differentiation stages or after extended incubation periods, most of the
      13C=O signals were found in the triacylglycerol (TG) molecules. Unsaturated 13C=O
      labeled acyl chains were detected in the TG molecules when cells were incubated
      with saturated 13C=O-labeled FFA, indicating that intracellular dehydrogenation
      had occurred in the 13C=O-labeled palmitoyl chain. By using 13C-labeled methyl
      myristate as an internal intensity reference, incorporation of 13C FFA into each
      acyl chain position of the major intracellular lipids was determined
      quantitatively.

PMID- 9625592
TI  - Effects of caffeine on lipoprotein lipase gene expression during the adipocyte
      differentiation process.
AB  - In this study, the effects of caffeine on lipoprotein lipase (LPL) gene
      expression were investigated in the 3T3-F442A preadipocyte cell line during the
      adipocyte differentiation process by determining LPL enzymatic activity and its
      messenger RNA (mRNA) level. The results demonstrate that caffeine acts on the
      gene expression of LPL, an early marker of adipocyte differentiation. It has a
      biphasic action: it increases gene expression in terms of mRNA when it is added
      to preadipocytes during the early stage of differentiation, but this is
      accompanied by a reduction of enzymatic activity. On the other hand, when
      caffeine is added for long periods during differentiation and/or when it is added
      to mature adipocytes, it induces marked inhibition of mRNA levels, correlated
      with a marked reduction of secreted enzymatic activity. The inhibitory effect of
      caffeine on LPL mRNA level can be reproduced by theophylline, a phosphodiesterase
      inhibitor, and by dibutyryl cyclic AMP, a non-metabolizable analog of cyclic AMP.
      However, the effect of caffeine and theophylline lasts longer than that of cyclic
      AMP, suggesting that a mechanism other than inhibition of cyclic AMP hydrolysis
      may be involved in the action of caffeine.

PMID- 9625593
TI  - Tocotrienols inhibit the growth of human breast cancer cells irrespective of
      estrogen receptor status.
AB  - Potential antiproliferative effects of tocotrienols, the major vitamin E
      component in palm oil, were investigated on the growth of both estrogen
      responsive (ER+) MCF7 human breast cancer cells and estrogen-unresponsive (ER-)
      MDA-MB-231 human breast cancer cells, and effects were compared with those of
      alpha-tocopherol (alphaT). The tocotrienol-rich fraction (TRF) of palm oil
      inhibited growth of MCF7 cells in both the presence and absence of estradiol with
      a nonlinear dose-response but such that complete suppression of growth was
      achieved at 8 microg/mL. MDA-MB-231 cells were also inhibited by TRF but with a
      linear dose-response such that 20 microg/mL TRF was needed for complete growth
      suppression. Separation of the TRF into individual tocotrienols revealed that all
      fractions could inhibit growth of both ER+ and ER- cells and of ER+ cells in both
      the presence and absence of estradiol. However, the gamma- and delta-fractions
      were the most inhibitory. Complete inhibition of MCF7 cell growth was achieved at
      6 microg/mL of gamma-tocotrienol/delta-tocotrienol (gammaT3/deltaT3) in the
      absence of estradiol and 10 microg/mL of deltaT3 in the presence of estradiol,
      whereas complete suppression of MDA-MB-231 cell growth was not achieved even at
      concentrations of 10 microg/mL of deltaT3. By contrast to these inhibitory
      effects of tocotrienols, alphaT had no inhibitory effect on MCF7 cell growth in
      either the presence or the absence of estradiol, nor on MDA-MB-231 cell growth.
      These results confirm studies using other sublines of human breast cancer cells
      and demonstrate that tocotrienols can exert direct inhibitory effects on the
      growth of breast cancer cells. In searching for the mechanism of inhibition,
      studies of the effects of TRF on estrogen-regulated pS2 gene expression in MCF7
      cells showed that tocotrienols do not act via an estrogen receptor-mediated
      pathway and must therefore act differently from estrogen antagonists.
      Furthermore, tocotrienols did not increase levels of growth-inhibitory insulin
      like growth factor binding proteins (IGFBP) in MCF7 cells, implying also a
      different mechanism from that proposed for retinoic acid inhibition of estrogen
      responsive breast cancer cell growth. Inhibition of the growth of breast cancer
      cells by tocotrienols could have important clinical implications not only because
      tocotrienols are able to inhibit the growth of both ER+ and ER- phenotypes but
      also because ER+ cells could be growth-inhibited in the presence as well as in
      the absence of estradiol. Future clinical applications of TRF could come from
      potential growth suppression of ER+ breast cancer cells otherwise resistant to
      growth inhibition by antiestrogens and retinoic acid.

PMID- 9625594
TI  - Effect of dietary arachidonic acid on metabolism of deuterated linoleic acid by
      adult male subjects.
AB  - The influence of dietary supplementation with 20:4n-6 on uptake and turnover of
      deuterium-labeled linoleic acid (18:2n-6[d2]) in human plasma lipids and the
      synthesis of desaturated and elongated n-6 fatty acids from 18:2n-6[d21 were
      investigated in six adult male subjects. The subjects were fed either a high
      arachidonic acid (HIAA) diet containing 1.7 g/d or a low-AA (LOAA) diet
      containing 0.21 g/d of AA for 50 d. Each subject was then dosed with about 3.5 g
      of 18:2n-6[d2] as the triglyceride (TG) at 8:00 A.M., 12:00, and 5:00 P.M. The
      total 18:2n-6[d21] fed to each subject was about 10.4 g and is approximately
      equal to one-half of the daily intake of 18:2n-6 in a typical U.S. male diet.
      Nine blood samples were drawn over a 96-h period. Methyl esters of plasma total
      lipid (TL), TG, phospholipid, and cholesterol ester were analyzed by gas
      chromatography-mass spectroscopy. Dietary 20:4n-6 supplementation did not affect
      uptake of 18:2n-6[d2] in plasma lipid classes over the 4-d study period nor the
      estimated half-life of 24-36 h for 18:2n-6[d2]. The percentages of major
      deuterium-labeled desaturation and elongation products in plasma TL, as a
      percentage of total deuterated fatty acids, were 1.35 and 1.34% 18:3n-6[d2]; 0.53
      and 0.50% 20:2n-6[d2]; 1.80 and 0.92% 20:3n-6[d2] and 3.13 and 1.51% 20:4n-6[d2]
      for the LOAA and HIAA diet groups, respectively. Trace amounts (<0.1%) of the
      22:4n-6[d2] and 22:5n-6[d2] metabolites were present. Plasma TL concentration
      data for both 20:3n-6[d2] and 20:4n-6[d2] were 48% lower (P < 0.05) in samples
      from the HIAA diet group than in samples from the LOAA diet group. For a normal
      adult male consuming a typical U.S. diet, the estimated accumulation in plasma TL
      of 20:4n-6 synthesized from 20 g/d (68 mmole) of 18:2n-6 is 677 mg/d (2.13
      mmole). Dietary supplementation with 1.5 g/d of 20:4n-6 reduced accumulation of
      20:4n-6 synthesized from 20 g/d of 18:2n-6 to about 326 mg/d (1.03 mmole).

PMID- 9625595
TI  - Effects of the ratio of polyunsaturated and monounsaturated fatty acid to
      saturated fatty acid on rat plasma and liver lipid concentrations.
AB  - The effects of dietary monounsaturated fatty acid (MUFA) and polyunsaturated
      fatty acid + MUFA/saturated fatty acid (PUFA + MUFA/SFA) ratio on plasma and
      liver lipid concentrations were studied. In experiment I, when rats were fed with
      40% fat (energy%, PUFA/SFA ratio 1.0) and 1% (w/w) cholesterol (C) diets for 21
      d, a large amount of MUFA (28.1 energy%, PUFA + MUFA/SFA = 5.7) in the diet was
      found to increase the plasma total C, triacylglycerol (TAG), and phospholipid
      (PL) as compared with the low-MUFA diet (7.0 energy%, PUFA + MUFA/SFA = 1.4). The
      plasma very low density lipoprotein (VLDL)-C, VLDL-TAG, VLDL-PL, and low density
      lipoprotein (LDL)-C increased significantly in the high-MUFA diet group, but high
      density lipoprotein (HDL)-C did not change significantly. The high-MUFA diet
      resulted in greater accumulation of liver C but lesser accumulation of TAG. In
      experiment II, when dietary SFA was fixed at a certain level (13.2 energy%; PUFA
      + MUFA/SFA = 2.0), rats given a larger amount of MUFA (23.1 energy%; PUFA/MUFA =
      0.2; MUFA/SFA = 1.8) showed higher plasma and liver C levels than did the low
      MUFA diet (7.7 energy%; PUFA/MUFA = 2.5; MUFA/SFA = 0.6). When PUFA was fixed at
      a certain level (24.4 energy%), there was not a significant difference in the
      plasma C level between the high- and low-MUFA dietary groups (PUFA + MUFA/SFA =
      4.8 and 8.4), but the higher PUFA + MUFA/SFA diet, which was high in MUFA/SFA
      ratio, significantly decreased the plasma HDL-C and TAG levels. However, when
      MUFA content was fixed at a certain level (16.4 energy%), no significant
      difference was observed between the two groups with different PUFA/SFA ratios of
      0.2 and 4.1, but liver C level was raised in the higher PUFA/SFA diet. It appears
      that the PUFA/SFA ratio alone is unsuitable to predict the change of plasma C
      level, because a large amount of dietary MUFA may lead to an increase of plasma
      and liver lipids in rats. It seems that the prerequisites for keeping low plasma
      and liver C are (i) low MUFA/SFA ratio, (ii) high PUFA/MUFA ratio, and (iii) PUFA
      + MUFA/SFA ratio not to exceed 2.

PMID- 9625597
TI  - Suppression of hypercholesterolemia in hepatoma-bearing rats by cabbage extract
      and its component, S-methyl-L-cysteine sulfoxide.
AB  - The effect of cabbage extract on cholesterol metabolism was studied in Donryu
      rats subcutaneously implanted with an ascites hepatoma cell line (AH109A). The
      hepatoma-bearing rats exhibited hypercholesterolemia induced by increasing
      cholesterogenesis in the host liver and decreasing steroid excretion into feces.
      The cabbage extract intake or administration reduced serum cholesterol level and
      enhanced fecal bile acid excretion and cholesterol 7alpha-hydroxylase activity,
      the rate-limiting enzyme of bile acid biosynthesis, in the microsomal fraction of
      the liver. Furthermore, S-methyl-L-cysteine sulfoxide, a component of cabbage,
      could mimic the effect of cabbage extract when orally administered. These results
      suggest that cabbage suppresses hypercholesterolemia responding to hepatoma
      growth by upregulating cholesterol catabolism and that S-methyl-L-cysteine
      sulfoxide in cabbage is one of the factors suppressing hypercholesterolemia in
      the hepatoma-bearing rats.

PMID- 9625596
TI  - Lipid-lowering effects of WAY-121,898, an inhibitor of pancreatic cholesteryl
      ester hydrolase.
AB  - WAY-121,898 is an inhibitor of pancreatic cholesteryl ester hydrolase (pCEH).
      After confirming its in vitro potency and relative lack of a major effect on acyl
      CoA:cholesterol acyltransferase (ACAT), it was found that this compound lowers
      plasma cholesterol in cholesterol-fed, but not chow-fed, rats. Measures of liver
      cholesteryl ester content and the direct determination of cholesterol absorption
      (lymph-fistula model) show that inhibition of cholesterol absorption is at least
      one mechanism for the observed cholesterol lowering. However, WAY-121,898 was
      also active when administered parenterally to cholesterol-fed rats, and in
      cholesterol-fed hamsters cholesterol-lowering occurred with oral dosing despite
      no change in cholesterol absorption, suggesting other modes of action possibly
      relating to inhibition of liver CEH. Combination treatment in cholesterol-fed
      rats with the ACAT inhibitor CI-976 resulted in a greater-than-additive reduction
      in plasma cholesterol, implying that both pCEH and ACAT may play a role in
      cholesterol absorption in this species. In rabbits, WAY-121,898 prevented the
      rise in plasma cholesterol due to the feeding of cholesteryl ester but not in
      rabbits fed (free) cholesterol. In guinea pigs, the compound induced an increase
      in adrenal cholesteryl ester mass. Taken together, the overall profile in these
      animal models suggests that WAY-121,898 inhibits more than just the intestinal
      (lumenal) pCEH, and that the role of this enzyme in cholesterol metabolism may be
      different within and across species, the former depending upon the dietary
      cholesterol load.

PMID- 9625598
TI  - Effect of n-3 fatty acid supplementation on lipid peroxidation and protein
      aggregation in rat erythrocyte membranes.
AB  - Human erythrocytes in the circulation undergo dynamic oxidative damage involving
      membrane lipid peroxidation and protein aggregation during aging. The present
      study was undertaken to determine the effect of n-3 fatty acid supplementation on
      lipid peroxidation and protein aggregation in the circulation and also the in
      vitro susceptibility of rat erythrocyte membranes to oxidative damage. Wistar
      male rats were fed a diet containing n-6 fatty acid-rich safflower oil or n-3
      fatty acid-rich fish oil with an equal amount of vitamin E for 6 wk. n-3 Fatty
      acid content in erythrocyte membranes of rats fed fish oil was significantly
      higher than that of rats fed safflower oil. The degree of membrane lipid
      peroxidation and protein aggregation of rats fed fish oil was not significantly
      higher than that of rats fed safflower oil when the amounts of phospholipid
      hydroperoxides, thiobarbituric acid-reactive substances, and detergent-insoluble
      protein aggregates were measured. When isolated erythrocytes were oxidized under
      aerobic conditions in the presence of Fe(III), the degree of membrane lipid
      peroxidation of erythrocytes from rats fed fish oil was increased to a greater
      extent than that of rats fed safflower oil, whereas the degree of membrane
      protein aggregation of both groups was increased in a similar extent. Hence, n-3
      fatty acid supplementation did not affect lipid peroxidation and protein
      aggregation in membranes of circulating rat erythrocytes, and the supplementation
      increased the susceptibility of isolated erythrocytes to lipid peroxidation, but
      not to protein aggregation, under the aerobic conditions. If a sufficient amount
      of vitamin E is supplied, n-3 fatty acid supplementation may give no undesirable
      oxidative effects on rat erythrocytes in the circulation.

PMID- 9625599
TI  - Modification of milk formula to enhance accretion of long-chain n-6 and n-3
      polyunsaturated fatty acids in artificially reared infant rats.
AB  - Artificially reared infant rats were used to determine the effects of long-chain
      polyunsaturated fatty acid (LCPUFA) supplementation on blood and tissue
      concentrations of arachidonic acid (AA) and docosahexaenoic acid (DHA). Beginning
      at 7 d of age, infant rats were fed for 10 d with rat milk formulas supplemented
      with AA at 0, 0.5 and 1.0%, or supplemented with DHA at 0, 0.5 and 1.0% of total
      fatty acid. The supplementation of AA increased accretion of the fatty acid in
      tissue and blood phospholipids with a maximum increase of 9% in brain, 15% in
      liver, 25% in erythrocytes, and 43% in plasma above the values of unsupplemented
      infant rats. Rat milk formula containing 1.0% of AA had no added benefits over
      that containing 0.5% of AA. The supplementation of DHA increased phospholipid DHA
      by a maximum of 24% in brain, 87% in liver, 54% in erythrocytes, and 360% in
      plasma above the unsupplemented control. The increase in tissue and blood DHA was
      concentration-dependent on formula fatty acid. Brain phosphatidylcholine and
      phosphatidylethanolamine were similarly enriched with AA and DHA by
      supplementation of the corresponding fatty acids. In general the observed
      increase of AA was accompanied by a decrease in 16:0, 18:1 n-9, and/or 18:2n-6,
      whereas the increased DHA was associated with a reduction of 18:1n-9, 18:2n-6,
      and/or 20:4n-6. Clearly, infant rats were more responsive to DHA than AA
      supplementation, suggesting a great potential of dietary manipulation to alter
      tissue DHA concentrations. However, the supplementation of DHA significantly
      decreased tissue and blood AA/DHA ratios (wt%/wt%), whereas there was little or
      no change in the ratio by AA supplementation. Although the physiological
      implications of the levels of AA and DHA, and AA/DHA ratios achieved under the
      present experimental conditions are not readily known, the findings suggest that
      artificial rearing could provide a suitable model to investigate LCPUFA
      requirements using various sources of AA and DHA in rats.

PMID- 9625600
TI  - Conjugated linoleic acid modulates tissue levels of chemical mediators and
      immunoglobulins in rats.
AB  - The effects of conjugated linoleic acid (CLA) on the levels of chemical mediators
      in peritoneal exudate cells, spleen and lung, and the concentration of
      immunoglobulins in mesenteric lymph node and splenic lymphocytes and in serum
      were examined in rats. After feeding diets containing either 0 (control), 0.5 or
      1.0% CLA for 3 wk, there was a trend toward a reduction in the release of
      leukotriene B4 (LTB4) from the exudate cells in response to the dietary CLA
      levels. However, CLA did not appear to affect the release of histamine. A similar
      dose-response pattern also was observed in splenic LTB4, lung LTC4 and serum
      prostaglandin E2 levels, and the differences in these indices between the control
      and 1.0% CLA groups were all statistically significant. The reduction by CLA of
      the proportions of n-6 polyunsaturated fatty acids in peritoneal exudate cells
      and splenic lymphocyte total lipids seems to be responsible at least in part for
      the reduced eicosanoid levels. Splenic levels of immunoglobulin A (IgA), IgG, and
      IgM increased while those of IgE decreased significantly in animals fed the 1.0%
      CLA diet. This was reflected in the serum levels of immunoglobulins. The levels
      of IgA, IgG, and IgM in mesenteric lymph node lymphocytes increased in a dose
      dependent manner, while IgE was reduced in those fed the higher CLA intake.
      However, no differences were seen in the proportion of T-lymphocyte subsets of
      mesenteric lymph node. These results support the view that CLA mitigates the food
      induced allergic reaction.

PMID- 9625601
TI  - Simultaneous quantitation of ceramides and 1,2-diacylglycerol in tissues by
      Iatroscan thin-layer chromatography-flame-ionization detection.
AB  - Ceramides and 1,2-diacylglycerol have been demonstrated in intracellular
      signaling pathways. A method of simultaneous mass determination of ceramides and
      1,2-diacylglycerol in tissues was developed using the latroscan which combines
      thin layer chromatography and flame ionization detection (TLC/FID) techniques.
      Because of relatively low amounts of these components in tissues, the fraction of
      nonpolar lipids, which included ceramides and glycerides, was eluted with
      chloroform/acetone mixture (3:1, vol/vol) through a silicic acid column to
      eliminate the polar phospholipids. Development of Chromarods was carried out
      using three solvent systems in a four-step development technique. The
      relationship of the peak area ratio to weight ratio compared with cholesteryl
      acetate added as an internal standard was linear. The amount of ceramides
      increased with incubation of rat heart homogenate and human erythrocyte membranes
      in the presence of sphingomyelinase (E.C. 3.1.4.12). The latroscan TLC/FID system
      provided a quick and reliable assessment of ceramides and 1,2-diacylglycerol.

PMID- 9625602
TI  - A gas chromatographic-mass spectrometric method using a PoraPLOT column for the
      detection of hydroperoxide lyase in Chlorella pyrenoidosa.
AB  - A gas chromatographic-mass spectrometric (GC-MS) method using a PoraPLOT Q column
      was developed for the analysis and identification of the volatile products
      produced by the action of hydroperoxide lyase (HPLS) upon 13-hydroperoxylinoleic
      or 13-hydroperoxylinolenic acids. The developed procedure required no
      derivatization, was not affected by the presence of water, did not require
      cryogenic conditions to be maintained during injection, and allowed for the
      quantitation of most products. An acetone powder preparation of Chlorella
      pyrenoidosa cells was triturated with borate buffer pH = 8.0, and the mixture
      centrifuged at 12,000 x g. The supernatant and pellet were assayed for HPLS
      activity by GC-MS analysis of the volatile products given by linoleic acid
      hydroperoxide. The data showed that the majority of HPLS activity resides in the
      pellet fraction, and that the primary volatile component was pentane, with
      smaller amounts of 2-(Z)-pentene and 1-pentene being produced. The fact that HPLS
      activity resides in the water-insoluble fraction of the acetone powder suggests
      that HPLS from Chlorella is a membrane-associated enzyme. This investigation also
      determined that a spectrophotometric assay using alcohol dehydrogenase for
      measuring HPLS activity was not specific, but measured enzymatic activity other
      than HPLS.

PMID- 9625603
TI  - Peroxisome-proliferating effects of fenoprofen in mice.
AB  - We report on hepatic effects obtained in vivo by treating mice with different
      doses of fenoprofen, an arylpropionic acid previously shown to inhibit in vitro
      peroxisomal very long chain fatty acid oxidation. A strong and dose-related
      induction of peroxisomal palmitoyl-CoA oxidase, and of carnitine acyltransferase
      and acyl-CoA hydrolase activities was recorded in liver homogenates of mice fed
      diets supplemented with different contents [0.01, 0.05, 0.1, or 1% (w/w)] of
      fenoprofen for 6 d. Peroxisomal glycolate oxidase and mitochondrial butyryl-CoA,
      octanoyl-CoA, and palmitoyl-CoA dehydrogenases were unaffected or increased.
      Hepatic catalase activity was significantly increased in mice fed the diet with
      0.05 and 0.1% fenoprofen but, surprisingly, was not stimulated in mice fed the 1%
      fenoprofen-containing diet. A time-related but unequal induction of acyl-CoA
      oxidases and catalase was observed with the 0.1% fenoprofen diet: at 21 d of
      treatment, the induction of lignoceroyl-CoA and palmitoyl-CoA oxidase activities
      were five-fold stronger than that of catalase activity. In mice treated with 1%
      fenoprofen for up to 6 d, only acyl-CoA oxidase activities were found to be
      significantly increased. Morphometric analysis of the liver peroxisomes in mice
      treated with 0.1% fenoprofen evidenced an increase in size, volume density, and
      surface density along with a reduced ratio between perimeter and area of the
      peroxisomal profiles. No morphological marker for very long chain fatty acid
      deposition could be detected in livers from fenoprofen-treated animals. Our
      findings clearly demonstrate that fenoprofen acts as a peroxisome proliferator in
      the liver of mice and do not support the occurrence of in vivo reduction of very
      long chain fatty acid oxidation in liver from treated animals.

PMID- 9625604
TI  - Maternal-fetal medicine and prenatal diagnosis.

PMID- 9625605
TI  - Biochemical engineering. Plant biotechnology. Web alert.

PMID- 9625606
TI  - Stefan Carrel memorial issue.

PMID- 9625607
TI  - Risk of recurrence after treatment of early breast cancer with skin-sparing
      mastectomy: another editorial perspective.

PMID- 9625608
TI  - [XXXV Annual meeting of the Spanish League Against Epilepsy. Seville, 21-22
      November 1997].

PMID- 9625609
TI  - The corpus luteum. Editor's formulation.

PMID- 9625610
TI  - A patient's guide to choosing unconventional therapies.
AB  - Unconventional therapies (UTs) are therapies not usually provided by Canadian
      physicians or other conventionally trained health care providers. Examples of
      common UTs available in Canada are herbal preparations, reflexology, acupuncture
      and traditional Chinese medicine. UTs may be used along with conventional
      therapies (complementary) or instead of conventional therapies (alternative).
      Surveys have shown that many Canadians use UTs, usually as complementary
      therapies, for a wide range of diseases and conditions. Reliable information
      about UTs is often difficult to find. Your doctor may be unable to give you
      specific advice or recommendations, since UTs are often not in a physician's area
      of expertise. However, he or she will usually be able to provide some general
      advice and help supervise your progress. For your own health and safety, it is
      important to keep your doctor informed of the choices you make. This document is
      intended to (a) provide you with questions to consider when making your treatment
      choices, (b) help you find information about UTs, (c) help you decide whether a
      specific UT is right for you, and (d) provide tips to help you evaluate the
      information you find.

PMID- 9625611
TI  - Intramedullary tuberculoma in a patient with human immunodeficiency virus
      infection and disseminated multidrug-resistant tuberculosis: case report.

PMID- 9625612
TI  - Paracoccidioidomycosis and tuberculosis in AIDS patients: report of two cases in
      Brazil.

PMID- 9625613
TI  - An AIDS patient with fever and pancytopenia.

PMID- 9625614
TI  - Progress in the development of a vaccine against schistosomiasis in China.

PMID- 9625615
TI  - Cautionary reflections.

PMID- 9625616
TI  - Arsenic carcinogenicity testing.

PMID- 9625617
TI  - Environmental lead is a problem in Lima, Peru.

PMID- 9625619
TI  - Biology and Conservation of Prosimians. Proceedings of an international
      conference. Chester, September 13-16, 1995.

PMID- 9625618
TI  - Oral treosulfan as second-line treatment in platinum-resistant ovarian cancer: a
      phase II study. The Danish Ovarian Cancer Study Group.
AB  - OBJECTIVE: To evaluate the effect of oral treosulfan in patients with platinum
      resistant ovarian cancer. METHODS: A phase II trial of oral treosulfan 500 mg per
      day in 30 females with platinum resistant ovarian cancer. All patients had
      measurable or evaluable disease. RESULTS: The treatment was well tolerated. One
      patient (3%) achieved a partial response lasting 12+ months. Seven patients had
      stable disease for 5.3 months (median) range 4.4-7.5 months. Median time to
      progression was 11.5 weeks (95% C.L. 11-12 weeks). Median survival was 31 weeks
      (95% C.L. 30-35 weeks). CONCLUSION: Oral treosulfan in the present schedule is
      not recommended in platinum resistant ovarian cancer.

PMID- 9625620
TI  - Images in clinical radiology. Intestinal taeniasis.

PMID- 9625621
TI  - Three-dimensional skeletal visualisation with spiral computed tomography.

PMID- 9625622
TI  - NMR functional imaging of the human brain.

PMID- 9625623
TI  - MAO--The Mother of all Amine Oxidases. Proceedings of the 6th Rappaport Symposium
      and 7th Amine Oxidase Workshop. Shavei Zion, Israel, June 1996. Dedicated to Dr
      Moise Da Prada.

PMID- 9625624
TI  - Rubrobramide, a cytotoxic and phytotoxic metabolite from Cladobotyrum
      rubrobrunnescens.
AB  - Cladobotrin (1) and rubrobramide (2) were isolated from the culture filtrate of
      Cladobotryum rubrobrunnescens, a mycophilic deuteriomycete. Rubrobramide (2),
      possessing a unique oxidized tricyclic system, is a new compound structurally
      related to flavipucine (3), which also is produced by the fungus. The structure
      of 2 was determined by spectroscopic methods. Cladobotrin (1) exhibited weak
      nematicidal activity toward Meldogyne incognita, while 2 showed weak cytotoxic
      and phytotoxic activities.

PMID- 9625626
TI  - JAMA patient page. Oh baby.

PMID- 9625625
TI  - Control of Pig Reproduction V. Proceedings of the 5th International Conference on
      Pig Reproduction. Kerkrade, The Netherlands, June 1997.

PMID- 9625627
TI  - [Methods to provide patients with information on antineoplastic agents].

PMID- 9625628
TI  - [Current status of transplantation of lungs from living donors].

PMID- 9625629
TI  - Images in clinical medicine. Cutaneous larva migrans.

PMID- 9625630
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 18-1998. A 54-day-old premature girl with respiratory distress
      and persistent pulmonary infiltrates.

PMID- 9625631
TI  - A mysterious death.

PMID- 9625632
TI  - Human cloning research.

PMID- 9625633
TI  - Human cloning research.

PMID- 9625634
TI  - Human cloning research.

PMID- 9625635
TI  - Hepatitis associated with hepatitis A superinfection in patients with chronic
      hepatitis C.

PMID- 9625636
TI  - Hepatitis associated with hepatitis A superinfection in patients with chronic
      hepatitis C.

PMID- 9625637
TI  - Hepatitis associated with hepatitis A superinfection in patients with chronic
      hepatitis C.

PMID- 9625638
TI  - Hepatitis associated with hepatitis A superinfection in patients with chronic
      hepatitis C.

PMID- 9625639
TI  - Epoprostenol (prostacyclin) therapy in primary pulmonary hypertension.

PMID- 9625640
TI  - Spinal and epidural hematoma and low-molecular-weight heparin.

PMID- 9625641
TI  - A computer-assisted management program for antiinfective agents.

PMID- 9625642
TI  - A computer-assisted management program for antiinfective agents.

PMID- 9625643
TI  - A computer-assisted management program for antiinfective agents.

PMID- 9625644
TI  - A computer-assisted management program for antiinfective agents.

PMID- 9625646
TI  - [Alternative measures against AIDS].

PMID- 9625645
TI  - Paronychia and pyogenic granuloma of the great toes in patients treated with
      indinavir.

PMID- 9625647
TI  - [Failing AIDS therapy].

PMID- 9625648
TI  - Who will minister to me?

PMID- 9625650
TI  - Note on retraction of the article of A. Jendryczko and M. Drozdz published in
      Przeglad Lekarski 1990, 47, 645-647.

PMID- 9625649
TI  - Communication breakdown.

PMID- 9625651
TI  - [Good practices in the use of tracheotomy cannulae at home. Ad hoc group of the
      Medical, Technical and Social Commission of ANTADIR].

PMID- 9625652
TI  - False-negative result in a microparticle enzyme immunoassay (MEIA) for the
      detection of antibodies to human immunodeficiency (HIV)

PMID- 9625653
TI  - Transient HBsAg detected after immunization with Engerix B.

PMID- 9625654
TI  - [Recruitment and training of researchers].

PMID- 9625655
TI  - [Chronic rhinitis in a cat as a sequela to a cleft palate].

PMID- 9625656
TI  - [The activities of the Task Force Laboratory for Hair Investigation of the
      Azerbaijani N. Narimanov State Medical Institute].

PMID- 9625657
TI  - [Dementia and self-determination].

PMID- 9625658
TI  - Therapeutic Options for Localized and Locally Advanced Prostate Cancer.
      Proceedings of a satellite symposium at the EAU-EUF meeting. Brussels, May 16,
      1997.

PMID- 9625660
TI  - Proceedings of the 7th International Conference on Aspartic Proteinases. Banff,
      Alberta, Canada. October 22-27, 1996.

PMID- 9625659
TI  - Proceedings of the 10th International Conference on Prostaglandins and Related
      Compounds. Vienna, Austria, September 22-27, 1996.

PMID- 9625661
TI  - American Psychological Association 1997 awards.

PMID- 9625662
TI  - Factor V Leiden mutation as a risk factor for recurrent pregnancy loss.
AB  - BACKGROUND: Recurrent pregnancy loss may result from hypercoagulability.
      OBJECTIVE: To determine whether women with factor V Leiden mutation, a common
      inherited defect of coagulation, are at increased risk for recurrent pregnancy
      loss. DESIGN: Case-control study. SETTING: University hospital. PATIENTS: 113
      consecutive women referred for evaluation of recurrent spontaneous abortion (case
      patients) and 437 postmenopausal women with at least one successful pregnancy and
      no history of pregnancy loss (controls). An additional survey of 387
      postmenopausal women with at least one pregnancy loss was also conducted.
      MEASUREMENTS: Prevalence of factor V Leiden mutation determined by a second
      generation screening test for resistance to activated protein C with genetic
      confirmation of all borderline and low-value results. RESULTS: Prevalence of the
      factor V Leiden mutation was greater among case-patients (8.0%) than among
      controls (3.7%) (odds ratio, 2.3 [95% CI, 1.0 to 5.2]; P = 0.050). In the
      subgroup of case-patients with three or more pregnancy losses and no successful
      pregnancies, prevalence of the mutation was 9.0% (odds ratio, 2.6 [CI, 1.0 to
      6.7]; P = 0.048). Among the additional women surveyed, the prevalence of the
      mutation in those with three or more pregnancy losses (7.5%) was almost identical
      to that in case-patients. Thus, in all evaluated women with several pregnancy
      losses, the prevalence of factor V Leiden was increased 2.2-fold (P = 0.026).
      CONCLUSION: These data are compatible with the hypothesis that factor V Leiden
      mutation may play a role in some cases of unexplained recurrent pregnancy loss.

PMID- 9625663
TI  - Cooperation: the foundation of improvement.
AB  - Cooperation--working together to produce mutual benefit or attain a common
      purpose--is almost inseparable from the quest for improvement. Although the case
      for cooperation can be made on ethical grounds, neither the motivation for nor
      the effects of cooperation need to be interpreted solely in terms of altruism.
      Cooperation can be a shrewd and pragmatic strategy for accomplishing personal
      goals in an interdependent system. Earlier papers in this series have explored
      the conceptual roots of modern approaches to improvement, which lie in systems
      theory. To improve systems, we must usually attend first and foremost to
      interactions. Among humans, "better interaction" is almost synonymous with
      "better cooperation." Physicians have ample opportunities and, indeed, an
      obligation to cooperate with other physicians in the same or different
      specialties, with nurses and other clinical workers, with administrators, and
      with patients and families. Many intellectual disciplines have made cooperation
      an object of study. These include anthropology; social psychology; genetics;
      biology; mathematics; game theory; linguistics; operations research; economics;
      and, of course, moral and rational philosophy. Scientifically grounded methods to
      enhance cooperation include developing a shared purpose; creating an open, safe
      environment; including all who share a common purpose and encouraging diverse
      viewpoints; negotiating agreement; and insisting on fairness and equity in the
      application of rules. These methods apply at the organizational level and at the
      level of the individual physician. This paper describes the application of these
      methods at the organizational level and focuses on one especially successful
      example of system-level cooperation in a care delivery site where interactions
      matter a great deal: the modern intensive care unit.

PMID- 9625664
TI  - The medical consultant's role in caring for patients with hip fracture.
AB  - BACKGROUND: Hip fractures are an important cause of death and functional
      dependence in the United States. PURPOSE: To review the evidence for clinical
      decisions that medical consultants make for patients with hip fracture and to
      develop recommendations for care. DATA SOURCES: Published reports of clinical
      studies were found by searching MEDLINE and selected bibliographies. STUDY
      SELECTION: Studies were included if data were presented on clinical interventions
      to improve care of conditions typically encountered by medical consultants in the
      care of patients with hip fracture. Such conditions include timing of surgery,
      infection prophylaxis, thromboembolic prophylaxis, postoperative nutritional
      management, urinary tract management, prevention and management of delirium,
      application and timing of rehabilitation services, and prevention of subsequent
      falls. Meta-analyses; randomized, controlled trials; or other controlled studies
      were included if possible. If no such trials were identified, the best evidence
      from studies with other designs was included. DATA EXTRACTION: Interventions were
      selected on the basis of their efficacy or potential efficacy in improving
      functional outcome. Trials with positive and negative results were compared for
      differences in intervention and strength of study methods. DATA SYNTHESIS: Strong
      evidence supports medical recommendations for decisions about timing and duration
      of prophylactic antibiotics, selection of thromboembolic prophylaxis, urinary
      tract and nutritional management, and rehabilitative services. Many case series
      support early surgical repair, although patients who would benefit from delay and
      further medical work-up have not been well identified. Evidence for decisions
      about assessment of subsequent risk for fall and risk for and management of
      delirium is based largely on data from patients without hip fracture but is
      probably applicable. Future research should target optimal duration of
      thromboembolic prophylaxis, cost-effectiveness of low-molecular-weight heparin
      compared with that of other thromboembolic prophylactic regimens, management of
      delirium, rehabilitative services, and efficacy of assessment of risk for later
      falls. CONCLUSIONS: The data suggest that evidence-based medical care can improve
      hip fracture outcomes. The medical consultant has a key role in providing this
      care and managing the preoperative conditions and postoperative complications
      that may affect optimal functional recovery.

PMID- 9625665
TI  - Use of cytotoxic agents and cyclosporine in the treatment of autoimmune disease.
      Part 1: rheumatologic and renal diseases.
AB  - When cytotoxic agents were initially introduced, their ability to disrupt nucleic
      acid and protein synthesis led to their effective use for the treatment of
      neoplastic disease. During the course of this use, however, it became apparent
      that these agents also suppress the immune system. This usually unwelcome effect
      was subsequently studied and beneficially directed toward the treatment of non
      neoplastic diseases in which autoimmune mechanisms were considered important to
      pathogenesis. As a result of these investigations, cytotoxic agents and, more
      recently, cyclosporine have emerged to become an important part of the
      therapeutic regimen for many autoimmune diseases. Nonetheless, these medications
      may still cause treatment-induced illness or even death. It is therefore
      particularly important to weigh the benefits and risks of cytotoxic therapy when
      treating a non-neoplastic disease. This two-part Clinical Staff Conference
      reviews data on the efficacy and toxicity of cytotoxic drugs and cyclosporine in
      selected autoimmune diseases. Part 1 examines the manner in which these agents
      have been used to treat rheumatologic and renal diseases.

PMID- 9625666
TI  - Traditional healers in southern Africa.
AB  - One task of medical anthropologists is to search for similarities and differences
      among cultural conceptions of illness and healing. This search may identify
      common, if not universal, characteristics of healing and effective patient care.
      This paper describes traditional healing practices in southern Africa as related
      by six traditional healers. Despite the seemingly exotic nature of their
      practice, the traditional healers' underlying strategies (probing deeply into the
      psychological, spiritual, and social contexts of illness and using healing
      ceremonies and natural medicinal preparations) seem to be effective in certain
      circumstances. Perhaps more important, these strategies can leave both patient
      and practitioner with a sense of connection and satisfaction. A study of these
      strategies reveals some general qualities of the healing process that are more
      apparent in the absence of sophisticated technology.

PMID- 9625667
TI  - Rehabilitation of the exercise electrocardiogram.

PMID- 9625668
TI  - Low-molecular-weight heparins in the treatment of venous thromboembolism.

PMID- 9625669
TI  - The knight of faith.

PMID- 9625670
TI  - Mark Twain's cat.

PMID- 9625671
TI  - Nitric oxide in cirrhosis.

PMID- 9625672
TI  - Megestrol acetate in the spectrum of adrenal insufficiency.

PMID- 9625673
TI  - Pertussis in adults.

PMID- 9625674
TI  - Pertussis in adults.

PMID- 9625675
TI  - Monitored isoniazid prophylaxis for low-risk tuberculin reactors.

PMID- 9625676
TI  - Dissolving phenytoin precipitate in central venous access device.

PMID- 9625677
TI  - Secretion of vasopressin from a human pheochromocytoma.

PMID- 9625678
TI  - Monitoring and regulating clinical software.

PMID- 9625679
TI  - The prison patient.

PMID- 9625680
TI  - New methods for drug delivery.

PMID- 9625681
TI  - Sickle cell anemia in adults: avoiding crises, organ damage.

PMID- 9625682
TI  - The electrocardiographic exercise test in a population with reduced workup bias:
      diagnostic performance, computerized interpretation, and multivariable
      prediction. Veterans Affairs Cooperative Study in Health Services #016 (QUEXTA)
      Study Group. Quantitative Exercise Testing and Angiography.
AB  - BACKGROUND: Empirical scores, computerized ST-segment measurements, and equations
      have been proposed as tools for improving the diagnostic performance of the
      exercise test. OBJECTIVE: To compare the diagnostic utility of these scores,
      measurements, and equations with that of visual ST-segment measurements in
      patients with reduced workup bias. DESIGN: Prospective analysis. SETTING: 12
      university-affiliated Veterans Affairs Medical Centers. PATIENTS: 814 consecutive
      patients who presented with angina pectoris and agreed to undergo both exercise
      testing and coronary angiography. MEASUREMENTS: Digital electrocardiographic
      recorders and angiographic calipers were used for testing at each site, and test
      results were sent to core laboratories. RESULTS: Although 25% of patients had
      previously had testing, workup bias was reduced, as shown by comparison with a
      pilot study group. This reduction resulted in a sensitivity of 45% and a
      specificity of 85% for visual analysis. Computerized measurements and visual
      analysis had similar diagnostic power. Equations incorporating
      nonelectrocardiographic variables and either visual or computerized ST-segment
      measurement had similar discrimination and were superior to single ST-segment
      measurements. These equations correctly classified 5 more patients of every 100
      tested (areas under the receiver-operating characteristic curve, 0.80 for
      equations and 0.68 for visual analysis; P < 0.001) in this population with a 50%
      prevalence of disease. CONCLUSIONS: Standard exercise tests had lower sensitivity
      but higher specificity in this population with reduced work-up bias than in
      previous studies. Computerized ST-segment measurements were similar to visual ST
      segment measurements made by cardiologists. Considering more than ST-segment
      measurements can enhance the diagnostic power of the exercise test.

PMID- 9625683
TI  - Ursodiol prophylaxis against hepatic complications of allogeneic bone marrow
      transplantation. A randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Hepatic complications are a major cause of illness and death after
      bone marrow transplantation. OBJECTIVE: To confirm the results of a pilot study
      that indicated that ursodiol prophylaxis could reduce the incidence of veno
      occlusive disease of the liver. DESIGN: Randomized, double-blind, placebo
      controlled study. SETTING: Tertiary care teaching hospital. PATIENTS: 67
      consecutive patients undergoing transplantation with allogeneic bone marrow
      (donated by a relative) in whom busulfan plus cyclophosphamide was used as the
      preparative regimen and cyclosporine plus methotrexate was used to prevent graft
      versus-host disease. INTERVENTION: Before the preparative regimen was started,
      patients were randomly assigned to receive ursodiol, 300 mg twice daily (or 300
      mg in the morning and 600 mg in the evening if body weight was > 90 kg), or
      placebo. MEASUREMENTS: Patients were prospectively evaluated for the clinical
      diagnosis of veno-occlusive disease, the occurrence of acute graft-versus-host
      disease, and survival. RESULTS: The incidence of veno-occlusive disease was 40%
      (13 of 32 patients) in placebo recipients and 15% (5 of 34 patients) in ursodiol
      recipients (P = 0.03). Assignment to placebo was the only pretransplantation
      characteristic that predicted the development of veno-occlusive disease. The most
      significant predictor of 100-day mortality was the diagnosis of veno-occlusive
      disease. The difference in actuarial risk for hematologic relapse in patients
      with chronic myelogenous leukemia and nonhepatic toxicities between the two
      groups was not statistically significant (13% in the ursodiol group and 20% in
      the placebo group; P > 0.2). CONCLUSION: Ursodiol prophylaxis seemed to decrease
      the incidence of hepatic complications after allogeneic bone marrow
      transplantation in patients who received a preparative regimen with busulfan plus
      cyclophosphamide.

PMID- 9625684
TI  - Use of enalapril to attenuate decline in renal function in normotensive,
      normoalbuminuric patients with type 2 diabetes mellitus. A randomized, controlled
      trial.
AB  - BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors attenuate the decline
      in renal function in diabetic patients with microalbuminuria. However, no data
      are available on the use of ACE inhibitors to prevent the decrease in renal
      function in normotensive, normoalbuminuric patients with type 2 diabetes.
      OBJECTIVE: To evaluate the effect of prolonged ACE inhibition on renal function
      and albuminuria in patients with type 2 diabetes. DESIGN: Randomized, double
      blind, placebo-controlled trial with 6-year follow-up. SETTING: Eight outpatient
      clinics coordinated by a department of medicine in a university hospital.
      PATIENTS: 156 patients in whom type 2 diabetes was diagnosed after 40 years of
      age who had a baseline mean blood pressure less than 107 mm Hg and albuminuria
      (albumin excretion < or = 30 mg/24 h). INTERVENTION: Enalapril, 10 mg/d, or
      placebo. MEASUREMENTS: Degree of albuminuria at 24 hours, creatinine clearance,
      blood pressure, and hemoglobin A1c values. RESULTS: Enalapril therapy decreased
      albumin excretion from a mean +/- SD of 11.6 +/- 7 mg/24 h to 9.7 +/- 6 mg/24 h
      at 2 years. This was followed by a gradual increase to 15.8 +/- 8 mg/24 h at 6
      years. In the placebo group, albumin excretion increased from 10.8 +/- 8 mg/24 h
      to 26.5 +/- 10 mg/24 h at 6 years (P = 0.001 for enalapril compared with
      placebo). Transition to microalbuminuria occurred in 15 of 79 (19%) placebo
      recipients and 5 of 77 (6.5%) enalapril recipients. Enalapril treatment resulted
      in an absolute risk reduction of 12.5% (95% CI, 2% to 23%; P = 0.042) for
      development of microalbuminuria. After 6 years, creatinine clearance decreased
      from 1.78 +/- 0.13 mL/s to 1.63 +/- 0.12 mL/s (mean decrease, 0.025 mL/s per
      year) in enalapril recipients and from 1.81 +/- 0.15 mL/s to 1.57 +/- 0.17 mL/s
      (mean decrease, 0.04 mL/s per year) in placebo recipients (P = 0.040). Hemoglobin
      A1c values decreased modestly in both groups. Mean blood pressure remained normal
      (< 107 mm Hg) in all patients. CONCLUSIONS: Enalapril attenuated the decline in
      renal function and reduced the extent of albuminuria in normotensive,
      normoalbuminuric patients with type 2 diabetes. Further research is needed to
      determine whether this treatment forestalls the development of overt nephropathy.

PMID- 9625685
TI  - Hospital-wide restriction of clindamycin: effect on the incidence of Clostridium
      difficile-associated diarrhea and cost.
AB  - BACKGROUND: Widespread antibiotic use has been associated with increases in both
      bacterial resistance and nosocomial infection. OBJECTIVE: To characterize the
      impact of hospital-wide clindamycin restriction on the incidence of Clostridium
      difficile-associated diarrhea and on antimicrobial prescribing practices. DESIGN:
      Prospective, observational cohort study. SETTING: University-affiliated Veterans
      Affairs Medical Center. PATIENTS: Hospitalized patients with symptomatic
      diarrhea. MEASUREMENTS: Clinical data on individual patients and data on
      antibiotic use were obtained from hospital pharmacy records. Hospital-wide use of
      antimicrobial agents was monitored. Isolates of C. difficile underwent
      antimicrobial susceptibility testing and molecular typing. RESULTS: An outbreak
      of C. difficile-associated diarrhea was caused by a clonal isolate of clindamycin
      resistant C. difficile and was associated with increased use of clindamycin.
      Hospital-wide requirement of approval by an infectious disease consultant of
      clindamycin use led to an overall reduction in clindamycin use, a sustained
      reduction in the mean number of cases of C. difficile-associated diarrhea (11.5
      cases/month compared with 3.33 cases/month; P < 0.001), and an increase in
      clindamycin susceptibility among C. difficile isolates (9% compared with 61%; P <
      0.001). A parallel increase was noted in the use of and costs associated with
      other antibiotics with antianaerobic activity, including cefotetan, ticarcillin
      clavulanate, and imipenem-cilastin. The hospital realized overall cost savings as
      a result of the decreased incidence of C. difficile-associated diarrhea.
      CONCLUSIONS: Hospital formulary restriction of clindamycin is an effective way to
      decrease the number of infections due to C. difficile. It can also lead to a
      return in clindamycin susceptibility among isolates and can effect cost savings
      to the hospital.

PMID- 9625686
TI  - Clinical reporting to primary care physicians leads to increased use and
      understanding of bone densitometry and affects the management of osteoporosis. A
      randomized trial.
AB  - BACKGROUND: A major barrier to wider use of bone densitometry has been a lack of
      reports that are comprehensible to primary care physicians. OBJECTIVE: To compare
      the effect of short technical reports and longer clinical reports on use,
      understanding, and acceptance of bone densitometry by primary care physicians and
      on management of osteoporosis. DESIGN: Randomized trial. SETTING: Osteoporosis
      center of a community teaching hospital. SUBJECTS: 57 primary care physicians
      ordering bone mineral density tests with dual x-ray absorptiometry. INTERVENTION:
      Physicians were randomly assigned to receive short technical reports or long
      clinical reports written by endocrinologists with access to clinical information.
      MEASUREMENTS: Physicians were interviewed by telephone after receiving at least
      two reports. RESULTS: Before being interviewed, physicians receiving short
      reports ordered a mean +/- SD of 0.72 +/- 0.71 tests per month; those receiving
      long reports ordered 1.30 +/- 1.21 tests per month (P = 0.002). At the first
      interview, 30% of physicians receiving short reports and 86% of those receiving
      long reports understood the bone mineral density definition of osteoporosis (P <
      0.001). Receiving long reports led to more modifications in the pharmacologic
      treatment of osteoporosis by gynecologists (19% of patients whose reports were
      short and 61% of patients whose reports were long; P = 0.021) and less confusion
      about reports by all physicians (36% of physicians receiving short reports and 1%
      of those receiving long reports; P = 0.003). CONCLUSIONS: Clinical reporting of
      bone densitometry to primary care physicians increased use and understanding of
      bone densitometry, changed management of osteoporosis, and was well accepted. It
      may help achieve appropriate use of bone densitometry and may allow convenient
      dissemination of information on osteoporosis.

PMID- 9625687
TI  - Polygalacturonases: many genes in search of a function.

PMID- 9625688
TI  - Temporal sequence of cell wall disassembly in rapidly ripening melon fruit 
AB  - The Charentais variety of melon (Cucumis melo cv Reticulatus F1 Alpha) was
      observed to undergo very rapid ripening, with the transition from the preripe to
      overripe stage occurring within 24 to 48 h. During this time, the flesh first
      softened and then exhibited substantial disintegration, suggesting that
      Charentais may represent a useful model system to examine the temporal sequence
      of changes in cell wall composition that typically take place in softening fruit.
      The total amount of pectin in the cell wall showed little reduction during
      ripening but its solubility changed substantially. Initial changes in pectin
      solubility coincided with a loss of galactose from tightly bound pectins, but
      preceded the expression of polygalacturonase (PG) mRNAs, suggesting early, PG
      independent modification of pectin structure. Depolymerization of polyuronides
      occurred predominantly in the later ripening stages, and after the appearance of
      PG mRNAs, suggesting the existence of PG-dependent pectin degradation in later
      stages. Depolymerization of hemicelluloses was observed throughout ripening, and
      degradation of a tightly bound xyloglucan fraction was detected at the early
      onset of softening. Thus, metabolism of xyloglucan that may be closely associated
      with cellulose microfibrils may contribute to the initial stages of fruit
      softening. A model is presented of the temporal sequence of cell wall changes
      during cell wall disassembly in ripening Charentais melon.

PMID- 9625689
TI  - Polygalacturonase gene expression in ripe melon fruit supports a role for
      polygalacturonase in ripening-associated pectin disassembly.
AB  - Ripening-associated pectin disassembly in melon is characterized by a decrease in
      molecular mass and an increase in the solubilization of polyuronide,
      modifications that in other fruit have been attributed to the activity of
      polygalacturonase (PG). Although it has been reported that PG activity is absent
      during melon fruit ripening, a mechanism for PG-independent pectin disassembly
      has not been positively identified. Here we provide evidence that pectin
      disassembly in melon (Cucumis melo) may be PG mediated. Three melon cDNA clones
      with significant homology to other cloned PGs were isolated from the rapidly
      ripening cultivar Charentais (C. melo cv Reticulatus F1 Alpha) and were expressed
      at high levels during fruit ripening. The expression pattern correlated
      temporally with an increase in pectin-degrading activity and a decrease in the
      molecular mass of cell wall pectins, suggesting that these genes encode
      functional PGs. MPG1 and MPG2 were closely related to peach fruit and tomato
      abscission zone PGs, and MPG3 was closely related to tomato fruit PG. MPG1, the
      most abundant melon PG mRNA, was expressed in Aspergillus oryzae. The culture
      filtrate exponentially decreased the viscosity of a pectin solution and catalyzed
      the linear release of reducing groups, suggesting that MPG1 encodes an endo-PG
      with the potential to depolymerize melon fruit cell wall pectin. Because MPG1
      belongs to a group of PGs divergent from the well-characterized tomato fruit PG,
      this supports the involvement of a second class of PGs in fruit ripening
      associated pectin disassembly.

PMID- 9625690
TI  - Gibberellins promote trichome formation by Up-regulating GLABROUS1 in arabidopsis
AB  - Trichome development is dependent on gibberellin (GA) signaling in Arabidopsis
      thaliana. Using the GA-deficient mutant ga1-3, the GA-response mutant spy-5, and
      uniconazol (a GA-biosynthesis inhibitor), we show that the GA level response
      correlates positively with both trichome number and trichome branch number. Two
      genes, GL1 and TTG, are required for trichome initiation. In ga1-3, coexpression
      of GL1 and R, the maize TTG functional homolog, under control of the constitutive
      35S promoter, restored trichome development, whereas overexpression of neither
      GL1 nor R alone was sufficient to significantly suppress the glabrous phenotype.
      We next focused on GL1 regulation by GAs. In the double mutant the gl1-1 glabrous
      phenotype is epistatic to the spy-5 phenotype, suggesting that GL1 acts
      downstream of the GA signal transduction pathway. The activity of a beta
      glucuronidase reporter gene driven by the GL1 promoter was decreased in the wild
      type grown on uniconazol and showed a clear GA-dependent activation in ga1-3.
      Finally, quantification of GL1 transcript levels by reverse transcriptase
      polymerase chain reaction demonstrated that relative to wild type, ga1-3 plants
      contained less transcript. These data support the hypothesis that GAs induce
      trichome development through up-regulation of GL1 and possibly TTG genes.

PMID- 9625691
TI  - Effects of oxygen on nodule physiology and expression of nodulins in alfalfa 
AB  - Early nodulin 2 (ENOD2) transcripts and protein are specifically found in the
      inner cortex of legume nodules, a location that coincides with the site of a
      barrier to O2 diffusion. The extracellular glycoprotein that binds the monoclonal
      antibody MAC236 has also been localized to this site. Thus, it has been proposed
      that these proteins function in the regulation of nodule permeability to O2
      diffusion. It would then be expected that the levels of ENOD2 mRNA/protein and
      MAC236 antigen would differ in nodules with different permeabilities to O2. We
      examined the expression of ENOD2 and other nodule-expressed genes in Rhizobium
      meliloti-induced alfalfa nodules grown under 8, 20, or 50% O2. Although there was
      a change in the amount of MAC236 glycoprotein, the levels of ENOD2 mRNA and
      protein did not differ significantly among nodules grown at the different [O2],
      suggesting that neither ENOD2 transcription nor synthesis is involved in the long
      term regulation of nodule permeability. Moreover, although nodules from all
      treatments reduced their permeability to O2 as the partial pressure of O2 (pO2)
      was increased to 100%, the levels of extractable ENOD2 and MAC236 proteins did
      not differ from those measured at the growth pO2, further suggesting that if
      these proteins are involved in a short-term regulation of the diffusion barrier,
      they must be involved in a way that does not require increased transcription or
      protein synthesis.

PMID- 9625692
TI  - Differential expression of the S-adenosyl-L-methionine synthase genes during pea
      development.
AB  - Two genes coding for S-adenosyl-l-methionine synthase (SAMS, EC 2.5. 1.6) were
      previously isolated from pea (Pisum sativum) ovaries. Both SAMS genes were highly
      homologous throughout their coding regions but showed a certain degree of
      sequence divergence within the 5' and the 3' untranslated regions. These regions
      have been used as gene-specific probes to analyze the differential expression of
      SAMS1 and SAMS2 genes in pea plants. The ribonuclease protection assay revealed
      different expression patterns for each individual gene. SAMS1 was strongly
      expressed in nearly all tissues, especially in roots. SAMS2 expression was
      weaker, reaching its highest level at the apex. Following pollination, SAMS1 was
      specifically up-regulated, whereas SAMS2 was expressed constitutively. The up
      regulation of SAMS1 during ovary development was also observed in unpollinated
      ovaries treated with auxins. In unpollinated ovaries an increase in SAMS1
      expression was observed as a consequence of ethylene production associated with
      the emasculation process. In senescing ovaries both SAMS1 and SAMS2 genes showed
      increased expression. Ethylene treatment of unpollinated ovaries led to an
      increase in the SAMS1 mRNA level. However, SAMS2 expression remained unchangeable
      after ethylene treatment, indicating that SAMS2 induction during ovary senescence
      was not ethylene dependent. SAMS mRNAs were localized by in situ hybridization at
      the endocarp of developing fruits and in the ovules of senescing ovaries. Our
      results indicate that the transcriptional regulation of SAMS genes is
      developmentally controlled in a specific way for each gene.

PMID- 9625693
TI  - An Arabidopsis VPS45p homolog implicated in protein transport to the vacuole.
AB  - The Sec1p family of proteins is required for vesicle-mediated protein trafficking
      between various organelles of the endomembrane system. This family includes
      Vps45p, which is required for transport to the vacuole in yeast (Saccharomyces
      cerevisiae). We have isolated a cDNA encoding a VPS45 homolog from Arabidopsis
      thaliana (AtVPS45). The cDNA is able to complement both the temperature-sensitive
      growth defect and the vacuolar-targeting defect of a yeast vps45 mutant,
      indicating that the two proteins are functionally related. AtVPS45p is a
      peripheral membrane protein that associates with microsomal membranes. Sucrose
      density gradient fractionation demonstrated that AtVPS45p co-fractionates with
      AtELP, a potential vacuolar protein sorting receptor, implying that they may
      reside on the same membrane populations. These results indicate that AtVPS45p is
      likely to function in the transport of proteins to the vacuole in plants.

PMID- 9625694
TI  - A gene coding for tomato fruit beta-galactosidase II is expressed during fruit
      ripening. Cloning, characterization, and expression pattern.
AB  - beta-Galactosidases (EC 3.2.1.23) constitute a widespread family of enzymes
      characterized by their ability to hydrolyze terminal, nonreducing beta-D
      galactosyl residues from beta-D-galactosides. Several beta-galactosidases,
      sometimes referred to as exo-galactanases, have been purified from plants and
      shown to possess in vitro activity against extracted cell wall material via the
      release of galactose from wall polymers containing beta(1-->4)-D-galactan.
      Although beta-galactosidase II, a protein present in tomato (Lycopersicon
      esculentum Mill.) fruit during ripening and capable of degrading tomato fruit
      galactan, has been purified, cloning of the corresponding gene has been elusive.
      We report here the cloning of a cDNA, pTombetagal 4 (accession no. AF020390),
      corresponding to beta-galactosidase II, and show that its corresponding gene is
      expressed during fruit ripening. Northern-blot analysis revealed that the beta
      galactosidase II gene transcript was detectable at the breaker stage of ripeness,
      maximum at the turning stage, and present at decreasing levels during the later
      stages of normal tomato fruit ripening. At the turning stage of ripeness, the
      transcript was present in all fruit tissues and was highest in the outermost
      tissues (including the peel). Confirmation that pTombetagal 4 codes for beta
      galactosidase II was derived from matching protein and deduced amino acid
      sequences. Furthermore, analysis of the deduced amino acid sequence of
      pTombetagal 4 suggested a high probability for secretion based on the presence of
      a hydrophobic leader sequence, a leader-sequence cleavage site, and three
      possible N-glycosylation sites. The predicted molecular mass and isoelectric
      point of the pTombetagal 4-encoded mature protein were similar to those reported
      for the purified beta-galactosidase II protein from tomato fruit.

PMID- 9625695
TI  - Characterization of SU1 isoamylase, a determinant of storage starch structure in
      maize.
AB  - Function of the maize (Zea mays) gene sugary1 (su1) is required for normal starch
      biosynthesis in endosperm. Homozygous su1- mutant endosperms accumulate a highly
      branched polysaccharide, phytoglycogen, at the expense of the normal branched
      component of starch, amylopectin. These data suggest that both branched
      polysaccharides share a common precursor, and that the product of the su1 gene,
      designated SU1, participates in kernel starch biosynthesis. SU1 is similar in
      sequence to alpha-(1-->6) glucan hydrolases (starch-debranching enzymes [DBEs]).
      Specific antibodies were produced and used to demonstrate that SU1 is a 79-kD
      protein that accumulates in endosperm coincident with the time of starch
      biosynthesis. Nearly full-length SU1 was expressed in Escherichia coli and
      purified to apparent homogeneity. Two biochemical assays confirmed that SU1
      hydrolyzes alpha-(1-->6) linkages in branched polysaccharides. Determination of
      the specific activity of SU1 toward various substrates enabled its classification
      as an isoamylase. Previous studies had shown, however, that su1- mutant
      endosperms are deficient in a different type of DBE, a pullulanase (or R enzyme).
      Immunoblot analyses revealed that both SU1 and a protein detected by antibodies
      specific for the rice (Oryza sativa) R enzyme are missing from su1- mutant
      kernels. These data support the hypothesis that DBEs are directly involved in
      starch biosynthesis.

PMID- 9625696
TI  - Activation of the maize anthocyanin gene a2 is mediated by an element conserved
      in many anthocyanin promoters.
AB  - Two transcription factors, C1 (a Myb-domain protein) and B (a basic-helix-loop
      helix protein), mediate transcriptional activation of the anthocyanin
      biosynthetic genes of maize (Zea mays). To begin to assess the mechanism of
      activation, the sequences required for C1- and B-mediated induction have been
      determined for the a2 promoter, which encodes an anthocyanin-biosynthetic enzyme.
      Analysis of a series of 7- to 13-base-pair substitutions revealed two regions
      crucial for activation. One region, centered at -99, contained a C1-binding site
      that abolished C1 binding. The other crucial region was adjacent, centered at 
      91. C1 binding was not detected at this site, and mutation of this site did not
      prevent C1 binding at -99. An oligonucleotide dimer containing these two crucial
      elements was sufficient for C1 and B activation of a heterologous promoter. These
      data suggest that activation of the anthocyanin genes involves C1 and another
      factor binding at closely adjacent sites. Mutating a previously postulated
      anthocyanin consensus sequence within a2 did not significantly reduce activation
      by C1 and B. However, sequence comparisons of the crucial a2 regions with
      sequences important for C1- and B-mediated activation in two other anthocyanin
      promoters led to a revised consensus element shared by these promoters.

PMID- 9625697
TI  - The role of EDTA in lead transport and accumulation by indian mustard 
AB  - Indian mustard (Brassica juncea) plants exposed to Pb and EDTA in hydroponic
      solution were able to accumulate up to 55 mmol kg-1 Pb in dry shoot tissue (1.1%
      [w/w]). This represents a 75-fold concentration of Pb in shoot tissue over that
      in solution. A threshold concentration of EDTA (0.25 mm) was found to be required
      to stimulate this dramatic accumulation of both Pb and EDTA in shoots. Below this
      threshold concentration, EDTA also accumulated in shoots but at a reduced rate.
      Direct measurement of a complex of Pb and EDTA (Pb-EDTA) in xylem exudate of
      Indian mustard confirmed that the majority of Pb in these plants is transported
      in coordination with EDTA. The accumulation of EDTA in shoot tissue was also
      observed to be directly correlated with the accumulation of Pb. Exposure of
      Indian mustard to high concentrations of Pb and EDTA caused reductions in both
      the transpiration rate and the shoot water content. The onset of these symptoms
      was correlated with the presence of free protonated EDTA (H-EDTA) in the
      hydroponic solution, suggesting that free H-EDTA is more phytotoxic than Pb-EDTA.
      These studies clearly demonstrate that coordination of Pb transport by EDTA
      enhances the mobility within the plants of this otherwise insoluble metal ion,
      allowing plants to accumulate high concentrations of Pb in shoots. The finding
      that both H-EDTA and Pb-EDTA are mobile within plants also has important
      implications for the use of metal chelates in plant nutritional research.

PMID- 9625698
TI  - Identification of the gene encoding the tryptophan synthase beta-subunit from
      Chlamydomonas reinhardtii.
AB  - We report the isolation of a Chlamydomonas reinhardtii cDNA that encodes the beta
      subunit of tryptophan synthase (TSB). This cDNA was cloned by functional
      complementation of a trp-operon-deleted strain of Escherichia coli. Hybridization
      analysis indicated that the gene exists in a single copy. The predicted amino
      acid sequence showed the greatest identity to TSB polypeptides from other
      photosynthetic organisms. With the goal of identifying mutations in the gene
      encoding this enzyme, we isolated 11 recessive and 1 dominant single-gene
      mutation that conferred resistance to 5-fluoroindole. These mutations fell into
      three complementation groups, MAA2, MAA7, and TAR1. In vitro assays showed that
      mutations at each of these loci affected TSB activity. Restriction fragment
      length polymorphism analysis suggested that MAA7 encodes TSB. MAA2 and TAR1 may
      act to regulate the activity of MAA7 or its protein product.

PMID- 9625699
TI  - Coordinate accumulation of antifungal proteins and hexoses constitutes a
      developmentally controlled defense response during fruit ripening in grape.
AB  - During ripening of grape (Vitis labruscana L. cv Concord) berries, abundance of
      several proteins increased, coordinately with hexoses, to the extent that these
      became the predominant proteins in the ovary. These proteins have been identified
      by N-terminal amino acid-sequence analysis and/or function to be a thaumatin-like
      protein (grape osmotin), a lipid-transfer protein, and a basic and an acidic
      chitinase. The basic chitinase and grape osmotin exhibited activities against the
      principal grape fungal pathogens Guignardia bidwellii and Botrytis cinerea based
      on in vitro growth assays. The growth-inhibiting activity of the antifungal
      proteins was substantial at levels comparable to those that accumulate in the
      ripening fruit, and these activities were enhanced by as much as 70% in the
      presence of 1 m glucose, a physiological hexose concentration in berries. The
      simultaneous accumulation of the antifungal proteins and sugars during berry
      ripening was correlated with the characteristic development of pathogen
      resistance that occurs in fruits during ripening. Taken together, accumulation of
      these proteins, in combination with sugars, appears to constitute a novel,
      developmentally regulated defense mechanism against phytopathogens in the
      maturing fruit.

PMID- 9625700
TI  - Metabolic bypass of the tricarboxylic acid cycle during lipid mobilization in
      germinating oilseeds. Regulation Of nad+-dependent isocitrate dehydrogenase
      versus fumarase 
AB  - Biosynthesis of sucrose from triacylglycerol requires the bypass of the CO2
      evolving reactions of the tricarboxylic acid (TCA) cycle. The regulation of the
      TCA cycle bypass during lipid mobilization was examined. Lipid mobilization in
      Brassica napus was initiated shortly after imbibition of the seed and proceeded
      until 2 d postimbibition, as measured by in vivo [1-14C]acetate feeding to whole
      seedlings. The activity of NAD+-isocitrate dehydrogenase (a decarboxylative
      enzyme) was not detected until 2 d postimbibition. RNA-blot analysis of B. napus
      seedlings demonstrated that the mRNA for NAD+-isocitrate dehydrogenase was
      present in dry seeds and that its level increased through the 4 d of the
      experiment. This suggested that NAD+-isocitrate dehydrogenase activity was
      regulated by posttranscriptional mechanisms during early seedling development but
      was controlled by mRNA level after the 2nd or 3rd d. The activity of fumarase (a
      component of the nonbypassed section of the TCA cycle) was low but detectable in
      B. napus seedlings at 12 h postimbibition, coincident with germination, and
      increased for the next 4 d. RNA-blot analysis suggested that fumarase activity
      was regulated primarily by the level of its mRNA during germination and early
      seedling development. It is concluded that posttranscriptional regulation of NAD+
      isocitrate dehydrogenase activity is one mechanism of restricting carbon flux
      through the decarboxylative section of the TCA cycle during lipid mobilization in
      germinating oilseeds.

PMID- 9625701
TI  - Stepwise photoinhibition of photosystem II. Studies with Synechocystis species
      PCC 6803 mutants with a modified D-E loop of the reaction center polypeptide D1.
AB  - Several mutant strains of Synechocystis sp. PCC 6803 with large deletions in the
      D-E loop of the photosystem II (PSII) reaction center polypeptide D1 were
      subjected to high light to investigate the role of this hydrophilic loop in the
      photoinhibition cascade of PSII. The tolerance of PSII to photoinhibition in the
      autotrophic mutant DeltaR225-F239 (PD), when oxygen evolution was monitored with
      2,6-dichloro-p-benzoquinone and the equal susceptibility compared with control
      when monitored with bicarbonate, suggested an inactivation of the QB-binding
      niche as the first event in the photoinhibition cascade in vivo. This step in PD
      was largely reversible at low light without the need for protein synthesis. Only
      the next event, inactivation of QA reduction, was irreversible and gave a signal
      for D1 polypeptide degradation. The heterotrophic deletion mutants DeltaG240-V249
      and DeltaR225-V249 had severely modified QB pockets, yet exhibited high rates of
      2,6-dichloro-p-benzoquinone-mediated oxygen evolution and less tolerance to
      photoinhibition than PD. Moreover, the protein-synthesis-dependent recovery of
      PSII from photoinhibition was impaired in the DeltaG240-V249 and DeltaR225-V249
      mutants because of the effects of the mutations on the expression of the psbA-2
      gene. No specific sequences in the D-E loop were found to be essential for high
      rates of D1 polypeptide degradation.

PMID- 9625702
TI  - Use of a new tetrazolium-based assay to study the production of superoxide
      radicals by tobacco cell cultures challenged with avirulent zoospores of
      phytophthora parasitica var nicotianae 
AB  - The relationship between the production of reactive oxygen species and the
      hypersensitive response (HR) of tobacco (Nicotiana tabacum L. ) toward an
      incompatible race of the Oomycete Phytophthora parasitica var nicotianae has been
      investigated. A new assay for superoxide radical (O2-) production based on
      reduction of the tetrazolium dye sodium,3'-(1-[phenylamino-carbonyl]-3, 4
      tetrazolium)-bis(4-methoxy-6-nitro) benzene-sulfonic acid hydrate (XTT) has
      enabled the quantitative estimation of perhydroxyl/superoxide radical acid-base
      pair (HO2./O2-) production during the resistant response. Tobacco suspension
      cells were inoculated with zoospores from compatible or incompatible races of the
      pathogen. Subsequent HO2./O2- production was monitored by following the formation
      of XTT formazan. In the incompatible interaction only, HO2./O2- was produced in a
      minor burst between 0 and 2 h and then in a major burst between 8 and 10 h
      postinoculation. During this second burst, rates of XTT reduction equivalent to a
      radical flux of 9.9 x 10(-15) mol min-1 cell-1 were observed. The HO2./O2-
      scavengers O2- dismutase and Mn(III)desferal each inhibited dye reduction. An HR
      was observed in challenged, resistant cells immediately following the second
      burst of radical production. Both scavengers inhibited the HR when added prior to
      the occurrence of either radical burst, indicating that O2- production is a
      necessary precursor to the HR.

PMID- 9625703
TI  - Auxin deprivation induces synchronous Golgi differentiation in suspension
      cultured tobacco BY-2 cells.
AB  - To date, the lack of a method for inducing plant cells and their Golgi stacks to
      differentiate in a synchronous manner has made it difficult to characterize the
      nature and extent of Golgi retailoring in biochemical terms. Here we report that
      auxin deprivation can be used to induce a uniform population of suspension
      cultured tobacco (Nicotiana tabacum cv BY-2) cells to differentiate synchronously
      during a 4-d period. Upon removal of auxin, the cells stop dividing, undergo
      elongation, and differentiate in a manner that mimics the formation of slime
      secreting epidermal and peripheral root-cap cells. The morphological changes to
      the Golgi apparatus include a proportional increase in the number of trans-Golgi
      cisternae, a switch to larger-sized secretory vesicles that bud from the trans
      Golgi cisternae, and an increase in osmium staining of the secretory products.
      Biochemical alterations include an increase in large, fucosylated, mucin-type
      glycoproteins, changes in the types of secreted arabinogalactan proteins, and an
      increase in the amounts and types of molecules containing the peripheral root-cap
      cell-specific epitope JIM 13. Taken together, these findings support the
      hypothesis that auxin deprivation can be used to induce tobacco BY-2 cells to
      differentiate synchronously into mucilage-secreting cells.

PMID- 9625705
TI  - The NAD(P)H dehydrogenase in barley thylakoids is photoactivatable and uses NADPH
      as well as NADH 
AB  - An improved light-dependent assay was used to characterize the NAD(P)H
      dehydrogenase (NDH) in thylakoids of barley (Hordeum vulgare L.). The enzyme was
      sensitive to rotenone, confirming the involvement of a complex I-type enzyme.
      NADPH and NADH were equally good substrates for the dehydrogenase. Maximum rates
      of activity were 10 to 19 &mgr;mol electrons mg-1 chlorophyll h-1, corresponding
      to about 3% of linear electron-transport rates, or to about 40% of ferredoxin
      dependent cyclic electron-transport rates. The NDH was activated by light
      treatment. After photoactivation, a subsequent light-independent period of about
      1 h was required for maximum activation. The NDH could also be activated by
      incubation of the thylakoids in low-ionic-strength buffer. The kinetics,
      substrate specificity, and inhibitor profiles were essentially the same for both
      induction strategies. The possible involvement of ferredoxin:NADP+ oxidoreductase
      (FNR) in the NDH activity could be excluded based on the lack of preference for
      NADPH over NADH. Furthermore, thenoyltrifluoroacetone inhibited the diaphorase
      activity of FNR but not the NDH activity. These results also lead to the
      conclusion that direct reduction of plastoquinone by FNR is negligible.

PMID- 9625704
TI  - Mutation of residue threonine-2 of the D2 polypeptide and its effect on
      photosystem II function in Chlamydomonas reinhardtii.
AB  - The D2 polypeptide of the photosystem II (PSII) complex in the green alga
      Chlamydomonas reinhardtii is thought to be reversibly phosphorylated. By analogy
      to higher plants, the phosphorylation site is likely to be at residue threonine-2
      (Thr-2). We have investigated the role of D2 phosphorylation by constructing two
      mutants in which residue Thr-2 has been replaced by either alanine or serine.
      Both mutants grew photoautotrophically at wild-type rates, and noninvasive
      biophysical measurements, including the decay of chlorophyll fluorescence, the
      peak temperature of thermoluminescence bands, and rates of oxygen evolution,
      indicate little perturbation to electron transfer through the PSII complex. The
      susceptibility of mutant PSII to photoinactivation as measured by the light
      induced loss of PSII activity in whole cells in the presence of the protein
      synthesis inhibitors chloramphenicol or lincomycin was similar to that of wild
      type. These results indicate that phosphorylation at Thr-2 is not required for
      PSII function or for protection from photoinactivation. In control experiments
      the phosphorylation of D2 in wild-type C. reinhardtii was examined by 32P
      labeling in vivo and in vitro. No evidence for the phosphorylation of D2 in the
      wild type could be obtained. [14C]Acetate-labeling experiments in the presence of
      an inhibitor of cytoplasmic protein synthesis also failed to identify
      phosphorylated (D2.1) and nonphosphorylated (D2.2) forms of D2 upon sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis. Our results suggest that the
      existence of D2 phosphorylation in C. reinhardtii is still in question.

PMID- 9625706
TI  - Tissue culture-specific expression of a naturally occurring tobacco feedback
      insensitive anthranilate synthase.
AB  - A cDNA and corresponding promoter region for a naturally occurring, feedback
      insensitive anthranilate synthase (AS) alpha-subunit gene, ASA2, has been
      isolated from an unselected, but 5-methyl-tryptophan-resistant (5MTr), tobacco
      (Nicotiana tabacum) cell line (AB15-12-1). The ASA2 cDNA contains a putative
      transit peptide sequence, and Southern hybridization shows that more than one
      closely related sequence is present in the tobacco genome. The ASA2 cDNA
      complemented a trpE nonsense mutant Escherichia coli strain, allowing growth on
      300 microm 5MT-containing minimal medium without tryptophan, and cell extracts
      contained feedback-insensitive AS activity. The 5MTr was lost when the E. coli
      strain was transformed with an ASA2 site-directed mutant (phenylalanine-107
      arginine-108 --> serine-107-glutamine-108). Identical nucleotide sequences
      encoding the phenylalanine-107-arginine-108 region have been found in polymerase
      chain reaction-amplified 326-bp ASA2 genomic fragments of wild-type (5-methyl
      tryptophan-sensitive [5MTs]) tobacco and a progenitor species. High-level ASA2
      transcriptional expression was detected only in 5MTr-cultured cells, not in 5MTs
      cells or in plants. Promoter studies indicate that tissue specificity of ASA2 is
      controlled by the promoter region between -2252 and -607. Since the ASA2 promoter
      sequences are not substantially different in the 5MTr and 5MTs lines, the
      increased levels of ASA2 mRNA in the 5MTr lines are most likely due to changes in
      a regulatory gene affecting ASA2 expression.

PMID- 9625707
TI  - Strontium-induced repetitive calcium spikes in a unicellular green alga 
AB  - The divalent cation Sr2+ induced repetitive transient spikes of the cytosolic
      Ca2+ activity [Ca2+]cy and parallel repetitive transient hyperpolarizations of
      the plasma membrane in the unicellular green alga Eremosphaera viridis. [Ca2+]cy
      measurements, membrane potential measurements, and cation analysis of the cells
      were used to elucidate the mechanism of Sr2+-induced [Ca2+]cy oscillations. Sr2+
      was effectively and rapidly compartmentalized within the cell, probably into the
      vacuole. The [Ca2+]cy oscillations cause membrane potential oscillations, and not
      the reverse. The endoplasmic reticulum (ER) Ca2+-ATPase blockers 2,5-di-tert
      butylhydroquinone and cyclopiazonic acid inhibited Sr2+-induced repetitive
      [Ca2+]cy spikes, whereas the compartmentalization of Sr2+ was not influenced. A
      repetitive Ca2+ release and Ca2+ re-uptake by the ER probably generated
      repetitive [Ca2+]cy spikes in E. viridis in the presence of Sr2+. The inhibitory
      effect of ruthenium red and ryanodine indicated that the Sr2+-induced Ca2+
      release from the ER was mediated by a ryanodine/cyclic ADP-ribose type of Ca2+
      channel. The blockage of Sr2+-induced repetitive [Ca2+]cy spikes by La3+ or Gd3+
      indicated the necessity of a certain influx of divalent cations for sustained
      [Ca2+]cy oscillations. Based on these data we present a mathematical model that
      describes the baseline spiking [Ca2+]cy oscillations in E. viridis.

PMID- 9625708
TI  - Function and substrate specificity of the gibberellin 3beta-hydroxylase encoded
      by the Arabidopsis GA4 gene.
AB  - cDNA corresponding to the GA4 gene of Arabidopsis thaliana L. (Heynh. ) was
      expressed in Escherichia coli, from which cell lysates converted [14C]gibberellin
      (GA)9 and [14C]GA20 to radiolabeled GA4 and GA1, respectively, thereby confirming
      that GA4 encodes a GA 3beta-hydroxylase. GA9 was the preferred substrate, with a
      Michaelis value of 1 microm compared with 15 microm for GA20. Hydroxylation of
      these GAs was regiospecific, with no indication of 2beta-hydroxylation or 2,3
      desaturation. The capacity of the recombinant enzyme to hydroxylate a range of
      other GA substrates was investigated. In general, the preferred substrates
      contained a polar bridge between C-4 and C-10, and 13-deoxy GAs were preferred to
      their 13-hydroxylated analogs. Therefore, no activity was detected using GA12
      aldehyde, GA12, GA19, GA25, GA53, or GA44 as the open lactone (20-hydroxy-GA53),
      whereas GA15, GA24, and GA44 were hydroxylated to GA37, GA36, and GA38,
      respectively. The open lactone of GA15 (20-hydroxy-GA12) was hydroxylated but
      less efficiently than GA15. In contrast to the free acid, GA25 19,20-anhydride
      was 3beta-hydroxylated to give GA13. 2,3-Didehydro-GA9 and GA5 were converted by
      recombinant GA4 to the corresponding epoxides 2, 3-oxido-GA9 and GA6.

PMID- 9625710
TI  - The role of gibberellin, abscisic acid, and sucrose in the regulation of potato
      tuber formation in vitro 
AB  - The effects of plant hormones and sucrose (Suc) on potato (Solanum tuberosum L.)
      tuberization were studied using in vitro cultured single-node cuttings. Tuber
      inducing (high Suc) and -noninducing (low Suc or high Suc plus gibberellin [GA])
      media were tested. Tuberization frequencies, tuber widths, and stolon lengths
      were measured during successive stages of development. Endogenous GAs and
      abscisic acid (ABA) were identified and quantified by high-performance liquid
      chromatography and gas chromatography-mass spectrometry. Exogenous GA4/7 promoted
      stolon elongation and inhibited tuber formation, whereas exogenous ABA stimulated
      tuberization and reduced stolon length. Indoleacetic acid-containing media
      severely inhibited elongation of stolons and smaller sessile tubers were formed.
      Exogenous cytokinins did not affect stolon elongation and tuber formation.
      Endogenous GA1 level was high during stolon elongation and decreased when stolon
      tips started to swell under inducing conditions, whereas it remained high under
      noninducing conditions. GA1 levels were negatively correlated with Suc
      concentration in the medium. We conclude that GA1 is likely to be the active GA
      during tuber formation. Endogenous ABA levels decreased during stolon and tuber
      development, and ABA levels were similar under inducing and noninducing
      conditions. Our results indicate that GA is a dominant regulator in tuber
      formation: ABA stimulates tuberization by counteracting GA, and Suc regulates
      tuber formation by influencing GA levels.

PMID- 9625709
TI  - Overexpression of iron superoxide dismutase in transformed poplar modifies the
      regulation of photosynthesis at low CO2 partial pressures or following exposure
      to the prooxidant herbicide methyl viologen.
AB  - Chloroplast-targeted overexpression of an Fe superoxide dismutase (SOD) from
      Arabidopsis thaliana resulted in substantially increased foliar SOD activities.
      Ascorbate peroxidase, glutathione reductase, and monodehydroascorbate reductase
      activities were similar in the leaves from all of the lines, but dehydroascorbate
      reductase activity was increased in the leaves of the FeSOD transformants
      relative to untransformed controls. Foliar H2O2, ascorbate, and glutathione
      contents were comparable in all lines of plants. Irradiance-dependent changes in
      net CO2 assimilation and chlorophyll a fluorescence quenching parameters were
      similar in all lines both in air (21% O2) and at low (1%) O2. CO2-response curves
      for photosynthesis showed similar net CO2-exchange characteristics in all lines.
      In contrast, values of photochemical quenching declined in leaves from
      untransformed controls at intercellular CO2 (Ci) values below 200 microL L-1 but
      remained constant with decreasing Ci in leaves of FeSOD transformants. When the
      O2 concentration was decreased from 21 to 1%, the effect of FeSOD overexpression
      on photochemical quenching at limiting Ci was abolished. At high light (1000
      micromol m-2 s-1) a progressive decrease in the ratio of variable (Fv) to maximal
      (Fm) fluorescence was observed with decreasing temperature. At 6(o)C the high
      light-induced decrease in the Fv/Fm ratio was partially prevented by low O2 but
      values were comparable in all lines. Methyl viologen caused decreased Fv/Fm
      ratios, but this was less marked in the FeSOD transformants than in the
      untransformed controls. These observations suggest that the rate of superoxide
      dismutation limits flux through the Mehler-peroxidase cycle in certain
      conditions.

PMID- 9625711
TI  - Transcriptional down-regulation by abscisic acid of pathogenesis-related beta-1,3
      glucanase genes in tobacco cell cultures.
AB  - Class I isoforms of beta-1,3-glucanases (betaGLU I) and chitinases (CHN I) are
      antifungal, vacuolar proteins implicated in plant defense. Tobacco (Nicotiana
      tabacum L.) betaGLU I and CHN I usually exhibit tightly coordinated
      developmental, hormonal, and pathogenesis-related regulation. Both enzymes are
      induced in cultured cells and tissues of cultivar Havana 425 tobacco by ethylene
      and are down-regulated by combinations of the growth hormones auxin and
      cytokinin. We report a novel pattern of betaGLU I and CHN I regulation in
      cultivar Havana 425 tobacco pith-cell suspensions and cultured leaf explants.
      Abscisic acid (ABA) at a concentration of 10 micron markedly inhibited the
      induction of betaGLU I but not of CHN I. RNA-blot hybridization and immunoblot
      analysis showed that only class I isoforms of betaGLU and CHN are induced in cell
      culture and that ABA inhibits steady-state betaGLU I mRNA accumulation.
      Comparable inhibition of beta-glucuronidase expression by ABA was observed for
      cells transformed with a tobacco betaGLU I gene promoter/beta-glucuronidase
      reporter gene fusion. Taken together, the results strongly suggest that ABA down
      regulates transcription of betaGLU I genes. This raises the possibility that some
      of the ABA effects on plant-defense responses might involve betaGLU I.

PMID- 9625712
TI  - A determinant of substrate specificity predicted from the acyl-acyl carrier
      protein desaturase of developing cat's claw seed.
AB  - Cat's claw (Doxantha unguis-cati L.) vine accumulates nearly 80% palmitoleic acid
      (16:1Delta9) plus cis-vaccenic acid (18:1Delta11) in its seed oil. To
      characterize the biosynthetic origin of these unusual fatty acids, cDNAs for acyl
      acyl carrier protein (acyl-ACP) desaturases were isolated from developing cat's
      claw seeds. The predominant acyl-ACP desaturase cDNA identified encoded a
      polypeptide that is closely related to the stearoyl (Delta9-18:0)-ACP desaturase
      from castor (Ricinis communis L.) and other species. Upon expression in
      Escherichia coli, the cat's claw polypeptide functioned as a Delta9 acyl-ACP
      desaturase but displayed a distinct substrate specificity for palmitate (16:0)
      ACP rather than stearate (18:0)-ACP. Comparison of the predicted amino acid
      sequence of the cat's claw enzyme with that of the castor Delta9-18:0-ACP
      desaturase suggested that a single amino acid substitution (L118W) might account
      in large part for the differences in substrate specificity between the two
      desaturases. Consistent with this prediction, conversion of leucine-118 to
      tryptophan in the mature castor Delta9-18:0-ACP desaturase resulted in an 80-fold
      increase in the relative specificity of this enzyme for 16:0-ACP. The alteration
      in substrate specificity observed in the L118W mutant is in agreement with a
      crystallographic model of the proposed substrate-binding pocket of the castor
      Delta9-18:0-ACP desaturase.

PMID- 9625713
TI  - Release of flavonoids by the soybean cultivars McCall and peking and their
      perception as signals by the nitrogen-fixing symbiont sinorhizobium fredii 
AB  - Sinorhizobium fredii strain USDA191 forms N-fixing nodules on the soybean
      (Glycine max L. Merr.) cultivars (cvs) McCall and Peking, but S. fredii strain
      USDA257 nodulates only cv Peking. We wondered whether specificity in this system
      is conditioned by the release of unique flavonoid signals from one of the
      cultivars or by differential perception of signals by the strains. We isolated
      flavonoids and used nodC and nolX, which are nod-box-dependent and -independent
      nod genes, respectively, to determine how signals activate genes in the
      microsymbionts. Seeds of cv McCall and cv Peking contain the isoflavones
      daidzein, genistein, and glycitein, as well as their glucosyl and malonylglucosyl
      glycosides. Roots exude picomolar concentrations of daidzein, genistein,
      glycitein, and coumestrol. Amounts are generally higher in cv Peking than in cv
      McCall, and the presence of rhizobia markedly influences the level of specific
      signals. Nanomolar concentrations of daidzein, genistein, and coumestrol induce
      expression of nodC and nolX in strain USDA257, but the relative nolX-inducing
      activities of these signals differ in strain USDA191. Glycitein and the
      conjugates are inactive. Strain USDA257 deglycosylates daidzin and genistin into
      daidzein and genistein, respectively, thereby converting inactive precursors into
      active inducers. Although neither soybean cultivar contains unique nod-gene
      inducing flavonoids, strain- and cultivar-specific interactions are characterized
      by distinct patterns of signal release and response.

PMID- 9625714
TI  - Correlation between binding affinity and necrosis-inducing activity of mutant
      AVR9 peptide elicitors.
AB  - The race-specific peptide elicitor AVR9 of the fungus Cladosporium fulvum induces
      a hypersensitive response only in tomato (Lycopersicon esculentum) plants
      carrying the complementary resistance gene Cf-9 (MoneyMaker-Cf9). A binding site
      for AVR9 is present on the plasma membranes of both resistant and susceptible
      tomato genotypes. We used mutant AVR9 peptides to determine the relationship
      between elicitor activity of these peptides and their affinity to the binding
      site in the membranes of tomato. Mutant AVR9 peptides were purified from tobacco
      (Nicotiana clevelandii) inoculated with recombinant potato virus X expressing the
      corresponding avirulence gene Avr9. In addition, several AVR9 peptides were
      synthesized chemically. Physicochemical techniques revealed that the peptides
      were correctly folded. Most mutant AVR9 peptides purified from potato virus
      X::Avr9-infected tobacco contain a single N-acetylglucosamine. These glycosylated
      AVR9 peptides showed a lower affinity to the binding site than the
      nonglycosylated AVR9 peptides, whereas their necrosis-inducing activity was
      hardly changed. For both the nonglycosylated and the glycosylated mutant AVR9
      peptides, a positive correlation between their affinity to the membrane-localized
      binding site and their necrosis-inducing activity in MoneyMaker-Cf9 tomato was
      found. The perception of AVR9 in resistant and susceptible plants is discussed.

PMID- 9625715
TI  - Increase in the quantum yield of photoinhibition contributes to copper toxicity
      in vivo 
AB  - The effect of copper on photoinhibition of photosystem II in vivo was studied in
      bean (Phaseolus vulgaris L. cv Dufrix). The plants were grown hydroponically in
      the presence of various concentrations of Cu2+ ranging from the optimum 0.3
      &mgr;m (control) to 15 &mgr;m. The copper concentration of leaves varied
      according to the nutrient medium from a control value of 13 mg kg-1 dry weight to
      76 mg kg-1 dry weight. Leaf samples were illuminated in the presence and absence
      of lincomycin at different light intensities (500-1500 &mgr;mol photons m-2 s-1).
      Lincomycin prevents the concurrent repair of photoinhibitory damage by blocking
      chloroplast protein synthesis. The photoinhibitory decrease in the light
      saturated rate of O2 evolution measured from thylakoids isolated from treated
      leaves correlated well with the decrease in the ratio of variable to maximum
      fluorescence measured from the leaf discs; therefore, the fluorescence ratio was
      used as a routine measurement of photoinhibition in vivo. Excess copper was found
      to affect the equilibrium between photoinhibition and repair, resulting in a
      decrease in the steady-state concentration of active photosystem II centers of
      illuminated leaves. This shift in equilibrium apparently resulted from an
      increase in the quantum yield of photoinhibition (PhiPI) induced by excess
      copper. The kinetic pattern of photoinhibition and the independence of PhiPI on
      photon flux density were not affected by excess copper. An increase in PhiPI may
      contribute substantially to Cu2+ toxicity in certain plant species.

PMID- 9625717
TI  - Desensitization of the perception system for chitin fragments in tomato cells 
AB  - Suspension-cultured tomato (Lycopersicon esculentum) cells react to stimulation
      by chitin fragments with a rapid, transient alkalinization of the growth medium,
      but behave refractory to a second treatment with the same stimulus (G. Felix, M.
      Regenass, T. Boller [1993] Plant J 4: 307-316). We analyzed this phenomenon and
      found that chitin fragments caused desensitization in a time- and concentration
      dependent manner. Partially desensitized cells exhibited a clear shift toward
      lower sensitivity of the perception system. The ability of chitin oligomers to
      induce desensitization depended on the degree of polymerization (DP), with DP5
      approximately DP4 >> DP3 >> DP2 > DP1. This correlates with the ability of these
      oligomers to induce the alkalinization response and to compete for the high
      affinity binding site on tomato cells and microsomal membranes, indicating that
      the alkalinization response and the desensitization process are mediated by the
      same receptor. The dose required for half-maximal desensitization was about 20
      times lower than the dose required for half-maximal alkalinization;
      desensitization could therefore be used as a highly sensitive bioassay for chitin
      fragments and chitin-related stimuli such as lipochitooligosaccharides
      (nodulation factors) from Rhizobium leguminosarum. Desensitization was not
      associated with increased inactivation of the stimulus or with a disappearance of
      high-affinity binding sites from the cell surface, and thus appears to be caused
      by an intermediate step in signal transduction.

PMID- 9625716
TI  - The chloroplast atpA gene cluster in Chlamydomonas reinhardtii. Functional
      analysis of a polycistronic transcription unit.
AB  - Most chloroplast genes in vascular plants are organized into polycistronic
      transcription units, which generate a complex pattern of mono-, di-, and
      polycistronic transcripts. In contrast, most Chlamydomonas reinhardtii
      chloroplast transcripts characterized to date have been monocistronic. This paper
      describes the atpA gene cluster in the C. reinhardtii chloroplast genome, which
      includes the atpA, psbI, cemA, and atpH genes, encoding the alpha-subunit of the
      coupling-factor-1 (CF1) ATP synthase, a small photosystem II polypeptide, a
      chloroplast envelope membrane protein, and subunit III of the CF0 ATP synthase,
      respectively. We show that promoters precede the atpA, psbI, and atpH genes, but
      not the cemA gene, and that cemA mRNA is present only as part of di-, tri-, or
      tetracistronic transcripts. Deletions introduced into the gene cluster reveal,
      first, that CF1-alpha can be translated from di- or polycistronic transcripts,
      and, second, that substantial reductions in mRNA quantity have minimal effects on
      protein synthesis rates. We suggest that posttranscriptional mRNA processing is
      common in C. reinhardtii chloroplasts, permitting the expression of multiple
      genes from a single promoter.

PMID- 9625718
TI  - Expression of small heat-shock proteins at low temperatures. A possible role in
      protecting against chilling injuries.
AB  - We previously reported that short exposure of tomato (Lycopersicon esculentum L.)
      fruits to high temperature protects them from chilling injury. To study the
      involvement of heat-shock proteins (HSPs) in the acquisition of low-temperature
      tolerance, we cloned two heat-shock-induced genes that are also expressed at low
      temperatures. The cloned cDNAs belong to the small HSP group. Sequence analyses
      of the clones showed perfect homology to the tomato-ripening gene tom66 and to
      the tomato chloroplastic HSP21 gene tom111. The expression of both genes was
      induced by high temperature in fruits, flowers, leaves, and stems, but not by low
      or ambient temperatures or by other stresses such as drought and anaerobic
      conditions. When the heated fruits were transferred to low temperature, tom66 and
      tom111 mRNA levels first decreased but were then reinduced. Induction was not
      observed in nonheated fruits at low temperature. Immunodetection of tom111
      encoded protein indicated that this protein is present at low temperatures in the
      heated fruits. The results of this study show that the expression of tom66 and
      tom111 is correlated with protection against some, but not all, symptoms of
      chilling injury.

PMID- 9625719
TI  - The kinetics of zeaxanthin formation is retarded by dicyclohexylcarbodiimide 
AB  - The de-epoxidation of violaxanthin to antheraxanthin (Anth) and zeaxanthin (Zeax)
      in the xanthophyll cycle of higher plants and the generation of nonphotochemical
      fluorescence quenching in the antenna of photosystem II (PSII) are induced by
      acidification of the thylakoid lumen. Dicyclohexylcarbodiimide (DCCD) has been
      shown (a) to bind to lumen-exposed carboxy groups of antenna proteins and (b) to
      inhibit the pH-dependent fluorescence quenching. The possible influence of DCCD
      on the de-epoxidation reactions has been investigated in isolated pea (Pisum
      sativum L.) thylakoids. The Zeax formation was found to be slowed down in the
      presence of DCCD. The second step (Anth --> Zeax) of the reaction sequence seemed
      to be more affected than the violaxanthin --> Anth conversion. Comparative
      studies with antenna-depleted thylakoids from plants grown under intermittent
      light and with unstacked thylakoids were in agreement with the assumption that
      binding of DCCD to antenna proteins is probably responsible for the retarded
      kinetics. Analyses of the DCCD-induced alterations in different antenna
      subcomplexes showed that Zeax formation in the PSII antenna proteins was
      predominantly influenced by DCCD, whereas Zeax formation in photosystem I was
      nearly unaffected. Our data support the suggestion that DCCD binding to PSII
      antenna proteins is responsible for the observed alterations in xanthophyll
      conversion.

PMID- 9625720
TI  - Effect of water stress on cell division and cell-division-cycle 2-like cell-cycle
      kinase activity in wheat leaves 
AB  - In wheat (Triticum aestivum) seedlings subjected to a mild water stress (water
      potential of -0.3 MPa), the leaf-elongation rate was reduced by one-half and the
      mitotic activity of mesophyll cells was reduced to 42% of well-watered controls
      within 1 d. There was also a reduction in the length of the zone of mesophyll
      cell division to within 4 mm from the base compared with 8 mm in control leaves.
      However, the period of division continued longer in the stressed than in the
      control leaves, and the final cell number in the stressed leaves reached 85% of
      controls. Cyclin-dependent protein kinase enzymes that are required in vivo for
      DNA replication and mitosis were recovered from the meristematic zone of leaves
      by affinity for p13(suc1). Water stress caused a reduction in H1 histone kinase
      activity to one-half of the control level, although amounts of the enzyme were
      unaffected. Reduced activity was correlated with an increased proportion of the
      34-kD Cdc2-like kinase (an enzyme sharing with the Cdc2 protein of other
      eukaryotes the same size, antigenic sites, affinity for p13(suc1), and H1 histone
      kinase catalytic activity) deactivated by tyrosine phosphorylation. Deactivation
      to 50% occurred within 3 h of stress imposition in cells at the base of the
      meristematic zone and was therefore too fast to be explained by a reduction in
      the rate at which cells reached mitosis because of slowing of growth; rather,
      stress must have acted more immediately on the enzyme. The operation of controls
      slowing the exit from the G1 and G2 phases is discussed. We suggest that a water
      stress signal acts on Cdc2 kinase by increasing phosphorylation of tyrosine,
      causing a shift to the inhibited form and slowing cell production.

PMID- 9625721
TI  - Allele-dependent barley grain beta-amylase activity.
AB  - The wild ancestor of cultivated barley, Hordeum vulgare subsp. spontaneum (K.
      Koch) A. & Gr. (H. spontaneum), is a source of wide genetic diversity, including
      traits that are important for malting quality. A high beta-amylase trait was
      previously identified in H. spontaneum strains from Israel, and transferred into
      the backcross progeny of a cross with the domesticated barley cv Adorra. We have
      used Southern-blot analysis and beta-amy1 gene characterization to demonstrate
      that the high beta-amylase trait in the backcross line is co-inherited with the
      beta-amy1 gene from the H. spontaneum parent. We have analyzed the beta-amy1 gene
      organization in various domesticated and wild-type barley strains and identified
      three distinct beta-amy1 alleles. Two of these beta-amy1 alleles were present in
      modern barley, one of which was specifically found in good malting barley
      cultivars. The third allele, linked with high grain beta-amylase activity, was
      found only in a H. spontaneum strain from the Judean foothills in Israel. The
      sequences of three isolated beta-amy1 alleles are compared. The involvement of
      specific intron III sequences, in particular a 126-bp palindromic insertion, in
      the allele-dependent expression of beta-amylase activity in barley grain is
      proposed.

PMID- 9625723
TI  - Saline stress alters the temporal patterns of xylem differentiation and
      alternative oxidase expression in developing soybean roots 
AB  - We conducted a coordinated biochemical and morphometric analysis of the effect of
      saline conditions on the differentiation zone of developing soybean (Glycine max
      L.) roots. Between d 3 and d 14 for seedlings grown in control or NaCl
      supplemented medium, we studied (a) the temporal evolution of the respiratory
      alternative oxidase (AOX) capacity in correlation with the expression and
      localization of AOX protein analyzed by tissue-print immunoblotting; (b) the
      temporal evolution and tissue localization of a peroxidase activity involved in
      lignification; and (c) the structural changes, visualized by light microscopy and
      quantified by image digitization. The results revealed that saline stress retards
      primary xylem differentiation. There is a corresponding delay in the temporal
      pattern of AOX expression, which is consistent with the xylem-specific
      localization of AOX protein and the idea that this enzyme is linked to xylem
      development. An NaCl-induced acceleration of the development of secondary xylem
      was also observed. However, the temporal pattern of a peroxidase activity
      localized in the primary and secondary xylem was unaltered by NaCl treatment.
      Thus, the NaCl-stressed root was specifically affected in the temporal patterns
      of AOX expression and xylem development.

PMID- 9625722
TI  - Wound signaling in tomato plants. Evidence that aba is not a primary signal for
      defense gene activation 
AB  - The effects of abscisic acid (ABA) on the accumulation of proteinase inhibitors I
      (Inh I) and II (Inh II) in young, excised tomato (Lycopersicon esculentum L.)
      plants were investigated. When supplied to excised plants through the cut stems,
      100 &mgr;m ABA induced the activation of the ABA-responsive le4 gene. However,
      under the same conditions of assay, ABA at concentrations of up to 100 &mgr;m
      induced only low levels of proteinase-inhibitor proteins or mRNAs, compared with
      levels induced by systemin or jasmonic acid over the 24 h following treatment. In
      addition, ABA only weakly induced the accumulation of mRNAs of several other
      wound-response proteins. Assays of the ABA concentrations in leaves following
      wounding indicated that the ABA levels increased preferentially near the wound
      site, suggesting that ABA may have accumulated because of desiccation. The
      evidence suggests that ABA is not a component of the wound-inducible signal
      transduction pathway leading to defense gene activation but is likely involved in
      the general maintenance of a healthy plant physiology that facilitates a normal
      wound response.

PMID- 9625724
TI  - Effects of xylem pH on transpiration from wild-type and flacca tomato leaves. A
      vital role for abscisic acid in preventing excessive water loss even from well
      watered plants 
AB  - The pH of xylem sap from tomato (Lycopersicon esculentum) plants increased from
      pH 5.0 to 8.0 as the soil dried. Detached wild-type but not flacca leaves
      exhibited reduced transpiration rates when the artificial xylem sap (AS) pH was
      increased. When a well-watered concentration of abscisic acid (0.03 &mgr;m) was
      provided in the AS, the wild-type transpirational response to pH was restored to
      flacca leaves. Transpiration from flacca but not from wild-type leaves actually
      increased in some cases when the pH of the AS was increased from 6.75 to 7.75,
      demonstrating an absolute requirement for abscisic acid in preventing stomatal
      opening and excessive water loss from plants growing in many different
      environments.

PMID- 9625725
TI  - A fruit-specific putative dihydroflavonol 4-reductase gene is differentially
      expressed in strawberry during the ripening process.
AB  - A cDNA clone encoding a putative dihydroflavonol 4-reductase gene has been
      isolated from a strawberry (Fragaria x ananassa cv Chandler) DNA subtractive
      library. Northern analysis showed that the corresponding gene is predominantly
      expressed in fruit, where it is first detected during elongation (green stages)
      and then declines and sharply increases when the initial fruit ripening events
      occur, at the time of initiation of anthocyanin accumulation. The transcript can
      be induced in unripe green fruit by removing the achenes, and this induction can
      be partially inhibited by treatment of de-achened fruit with naphthylacetic acid,
      indicating that the expression of this gene is under hormonal control. We propose
      that the putative dihydroflavonol 4-reductase gene in strawberry plays a main
      role in the biosynthesis of anthocyanin during color development at the late
      stages of fruit ripening; during the first stages the expression of this gene
      could be related to the accumulation of condensed tannins.

PMID- 9625726
TI  - Biochemistry, biology, and carcinogenicity of tobacco-specific N-nitrosamines.

PMID- 9625727
TI  - Nitrotyrosine-protein adducts in hepatic centrilobular areas following toxic
      doses of acetaminophen in mice.
AB  - Treatment of mice with a toxic dose of acetaminophen (300 mg/kg, ip)
      significantly increased hepatotoxicity at 4 h, as evidenced by histological
      necrosis in the centrilobular areas of the liver, and increased serum levels of
      alanine aminotransferase (ALT) (from 8 +/- 1 IU/L in saline-treated mice to 3226
      +/- 892 IU/L in the acetaminophen-treated mice). Serum levels of nitrate plus
      nitrite (a marker of nitric oxide synthesis) were also increased from 62 +/- 8
      microM in saline-treated mice to 110 +/- 14 microM in acetaminophen-treated mice
      (P < 0.05). Regression analysis of serum ALT levels to serum nitrate plus nitrite
      levels in individual mice revealed a positive, linear relationship between serum
      ALT levels and serum nitrate plus nitrite levels with a correlation coefficient
      of 0.9 (P < 0.05). The y intercept value (nitrate plus nitrite level) was 63 +/-
      15 microM. Immunohistochemical analysis of liver sections from acetaminophen
      intoxicated mice using an anti-3-nitrotyrosine antibody indicated tyrosine
      nitration in the proteins of the centrilobular cells. Tyrosine nitration has been
      shown to occur by peroxynitrite, a reactive intermediate formed by an extremely
      rapid reaction of nitric oxide and superoxide and a species which also has
      hydroxyl radical-like activity. Analysis of liver sections using an anti
      acetaminophen antiserum indicated the centrilobular cells also contained
      acetaminophen-protein adducts, a reaction of the metabolite N-acetyl-p
      benzoquinone imine with cysteine residues on proteins. These data are consistent
      with acetaminophen metabolic activation leading to increased synthesis of nitric
      oxide and superoxide and to peroxynitrite as an important intermediate in the
      toxicity.

PMID- 9625728
TI  - Inhibition of nitric oxide formation by neuronal nitric oxide synthase by
      quinones: nitric oxide synthase as a quinone reductase.
AB  - Inhibitory action of a variety of quinoid compounds on neuronal nitric oxide
      synthase (nNOS) activity was examined with a 20000g rat cerebellar supernatant
      preparation and purified nNOS. The inhibition of citrulline formation from l
      arginine by quinones, which exhibit one-electron reduction potentials (E17)
      ranging between -240 and -100 mV, increased at a more positive one-electron
      reduction potential, suggesting that quinone appears to act as an electron
      acceptor for nNOS. Among the quinones tested, 9,10-phenanthraquinone (PQ),
      corresponding to an E17 value of -124 mV, exhibited the most potent inhibiton of
      citrulline formation (IC50 value = 10 microM). A kinetic study revealed that PQ
      is a competitive inhibitor with respect to NADPH, with a Ki value of 0.38 +/-
      0.12 microM, and a noncompetitive inhibitor with respect to l-arginine, with a Ki
      value of 9.63 +/- 0.20 microM. Partial purification of the enzymes which are
      responsible for reducing PQ in 20000g supernatant of rat cerebellum by anion
      exchange column chromatography indicated that one catalyst for PQ reduction was
      nNOS. Reductase activity of PQ by purified nNOS required CaCl2/calmodulin and was
      markedly suppressed by the flavoprotein inhibitor diphenyleneiodonium but not by
      l-nitroarginine which is a specific inhibitor for NO formation. nNOS effectively
      reduced the quinones as well as PQ causing a marked decrease in the production of
      NO from l-arginine, while 1, 4-benzoquinone, 9,10-anthraquinone, mitomycin C, and
      lapachol, which show negligible inhibitory action on nNOS activity, were poor
      substrates for the enzyme on reduction. These results indicate that PQ and other
      quinones used in the present study interact with the NADPH-cytochrome P450
      reductase domain on nNOS and thus probably inhibit NO formation by shunting
      electrons away from the normal catalytic pathway. Therefore, our study suggests
      that quinones could possibly affect NO-dependent physiological and/or
      pathophysiological actions in vivo.

PMID- 9625729
TI  - Characterization of hemoglobin adducts from a 4, 4'-methylenedianiline metabolite
      evidently produced by peroxidative oxidation in vivo.
AB  - 4,4'-Methylenedianiline (MDA) is a widely used mutagenic and carcinogenic
      industrial chemical. It is also a metabolite of 4, 4'-methylenediphenyl
      diisocyanate (MDI), which is used in the manufacturing of polyurethane foams.
      Biomonitoring of MDA, like other aromatic amines, is mainly carried out by GC/MS
      measurement of cysteine adducts in Hb from the nitroso metabolite, released by
      alkaline hydrolysis. In the present study it was investigated whether the
      formation of Hb adducts from non-nitroso metabolites of MDA can be used for the
      dosimetry of MDA. The study was carried out by treatment of mice with MDA and
      tritiated MDA or deuterated MDA and by identification of their products of
      reaction with Hb, after enzymatic hydrolysis of the globin and enrichment of the
      adducts. The main adduct, about 50% of the total amount of MDA associated with
      Hb, was characterized by MS and was shown to be a reaction product of MDA and the
      amino group of N-terminal valine in Hb, the derived structure being 1-[(4-imino
      2, 5-cyclohexadien-1-ylidene)methyl]benzene-4-azo-2-isovaleric acid. It is likely
      that this quinonoid MDA imine adduct to valine was formed by an attack of a
      metabolite formed through peroxidative oxidation of MDA, in analogy with earlier
      observed oxidation of some other aromatic amines, e.g., benzidine. The reactive
      intermediate is suggested to be [(4-imino-2, 5-cyclohexadien-1-ylidene)methyl]-4
      aminobenzene. The formation of the adduct was confirmed by incubating MDA with
      valine methyl ester in vitro in the presence of H2O2 and lactoperoxidase.
      Further, the same adduct was detected in MDI-exposed and control rats, the level
      in the exposed animals being about 60 times higher than in the controls. This
      study indicates that, at least in the mouse, extrahepatic peroxidative metabolism
      is an important pathway for the bioactivation of MDA, possibly leading to a
      genotoxic reactive intermediate. This study also demonstrates the usefulness of
      Hb adduct analysis for the identification of reactive intermediates in vivo.

PMID- 9625730
TI  - Detection of weak estrogenic flavonoids using a recombinant yeast strain and a
      modified MCF7 cell proliferation assay.
AB  - A newly developed recombinant yeast strain, in which the human estrogen receptor
      has been stably integrated into the genome of the yeast, was used to gain
      information on the estrogenic activity of a large series of dietary flavonoids.
      Among 23 flavonoids investigated, 8 were found to markedly stimulate the
      transcriptional activity of the human estrogen receptor in the yeast assay
      increasing transcriptional activity 5-13-fold above background level,
      corresponding to EC50 values between 0.1 and 25 microM. Five compounds increased
      the transcriptional activity 2-5-fold over the control, with EC50 values ranging
      from 84 to 102 microM, whereas the remaining flavonoids were devoid of activity.
      The most potent flavonoid estrogens tested were naringenin, apigenin, kaempferol,
      phloretin, and the four isoflavonoids equol, genistein, daidzein, and biochanin
      A. With the exception of biochanin A, the main feature required to confer
      estrogenicity was the presence of a single hydroxyl group in the 4'-position of
      the B-ring of the flavan nucleus, corresponding to the 4-position on phloretin.
      The estrogenic potency of the flavonoids was found to be 4 000-4 000 000 times
      lower than that observed for 17beta-estradiol, when compared on the basis of EC50
      values. The estrogenic activity of the dietary flavonoids was further
      investigated in estrogen-dependent human MCF7 breast cancer cells. In this system
      several of the flavonoids were likewise capable of mimicking natural estrogens
      and thereby induce cell proliferation. Similar structural requirements for
      estrogenic activity were found for the two assays. The present results provide
      evidence that several of the flavo-estrogens possess estrogenic properties
      comparable in activity to the well-established isoflavonoid estrogens. The use of
      Alamar Blue, a vital dye which is metabolically reduced by cellular enzymes to a
      fluorescent product, was found to greatly simplify the MCF7 cell-based estrogen
      screen, making this mammalian assay applicable as a large-scale screening tool
      for estrogenic compounds.

PMID- 9625731
TI  - Halide effects in the hydrolysis reactions of (+/-)-7beta, 8alpha-dihydroxy
      9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo- [a]pyrene.
AB  - Rates of reaction of (+/-)-7beta,8alpha-dihydroxy-9alpha, 10alpha-epoxy-7,8,9,10
      tetrahydrobenzo[a]pyrene (DE-2) have been determined in 1:9 dioxane-water
      solutions containing 1.0 M KCl, 0.5 M KBr, and 0.1 M NaI over the pH range 4-13.
      These pH-rate profiles are more complicated than those for reaction of DE-2 in
      0.2 M NaClO4 solutions and are interpreted in part by mechanisms in which halide
      ion attacks the diol epoxide as a nucleophile at intermediate pH, resulting in
      the formation of a trans-halohydrin. Reaction of DE-2 in these halide solutions
      at pH < ca. 5 occurs by rate-limiting carbocation formation, followed by capture
      of the intermediate carbocation by halide ion. The relative magnitudes of the
      rate constants for reaction of the intermediate carbocation with halide ions are
      estimated from product studies. The halohydrins are unstable intermediates and
      react quickly in subsequent reactions to yield tetrols in a ratio different than
      that formed from reaction of the carbocation with solvent. Nucleophilic attacks
      of 1.0 M Cl-, 0.5 M Br-, and 0.1 M I- on DE-2 are the principal reactions in the
      pH range ca. 6-9, leading to intermediate trans-halohydrins that hydrolyze to
      tetrols. At pH ca. 9-11, halohydrin formed from attack of halide ion on DE-2
      reverts back to epoxide, leading to a negative break in the pH-rate profile. The
      main product-forming reaction of DE-2 at pH 11.3 is the spontaneous reaction. At
      pH > 12, the rate of reaction of DE-2 increases due to a second-order reaction of
      HO- with DE-2.

PMID- 9625732
TI  - Oxidation of serotonin by superoxide radical: implications to neurodegenerative
      brain disorders.
AB  - Many new lines of evidence implicate both superoxide anion radical (O2*-) and
      biogenic amine neurotransmitters in the pathological mechanisms that underlie
      neuronal damage caused by methamphetamine (MA), glutamate-mediated oxidative
      toxicity, ischemia-reperfusion, and other neurodegenerative brain disorders. In
      this investigation the oxidation of 5-hydroxytryptamine (5-HT, serotonin) by an
      O2*--generating system (xanthine/xanthine oxidase) in buffered aqueous solution
      at pH 7.4 has been studied. The major product of the O2*--mediated oxidation of 5
      HT is tryptamine-4,5-dione (T-4, 5-D). However, O2*- and H2O2, cogenerated by the
      xanthine oxidase-mediated oxidation of xanthine to uric acid, together react with
      trace levels of iron that contaminate buffer constituents to give a chemically
      ill-defined oxo-iron species. This species mediates the oxidation of 5-HT to a
      C(4)-centered carbocation intermediate that reacts with 5-HT to give 5,5'
      dihydroxy-4, 4'-bitryptamine (4,4'-D) and with uric acid to give 9-[3-(2
      aminoethyl)-5-hydroxy-1H-indol-4-yl]-2,6,8-triketo-1H,3H, 7H-purine (7) as the
      major products. These products differ from those formed in the HO*-mediated
      oxidation of 5-HT under similar conditions. When the reaction is carried out in
      the presence of the intraneuronal nucleophile glutathione (GSH), T-4,5-D is
      scavenged to give 7-(S-glutathionyl)tryptamine-4,5-dione, whereas the putative
      carbocation intermediate is scavenged to give 4-(S-glutathionyl)-5
      hydroxytryptamine. T-4,5-D also reacts with the sulfhydryl residues of a model
      protein, alcohol dehydrogenase, and inhibits its activity. Previous investigators
      have proposed that T-4, 5-D is a serotonergic neurotoxin. This raises the
      possibility that T-4,5-D and perhaps other putative intraneuronal metabolites
      formed by the O2*-/H2O2/oxo-iron-mediated oxidations of 5-HT might be endotoxins
      that contribute to neurodegeneration in brain regions innervated by serotonergic
      neurons caused by MA, ischemia-reperfusion, and other neurodegenerative brain
      disorders.

PMID- 9625733
TI  - Biotransformation of 12C- and 2-13C-labeled methyl tert-butyl ether, ethyl tert
      butyl ether, and tert-butyl alcohol in rats: identification of metabolites in
      urine by 13C nuclear magnetic resonance and gas chromatography/mass spectrometry.
AB  - The biotransformation of the fuel oxygenates methyl tert-butyl ether (MTBE) and
      ethyl tert-butyl ether (ETBE) was studied in rats after inhalation exposure; the
      biotransformation of the initial metabolite of these ethers, tert-butyl alcohol,
      was studied after oral gavage. To study ether metabolism, rats were exposed for 6
      h to initial concentrations of 2000 ppm of MTBE or ETBE, respectively [2-13C]MTBE
      and [2-13C]ETBE. Urine was collected for 48 h after the end of the exposure, and
      urinary metabolites were identified by 13C NMR (13C-labeled ethers) and gas
      chromatography/mass spectrometry (GC/MS) (12C- and 13C-labeled ethers). To study
      tert-butyl alcohol metabolism, rats were dosed either with tert-butyl alcohol at
      natural carbon isotope ratio or with 13C-enriched tert-butyl alcohol (250 mg/kg
      of body weight), urine was collected, and metabolites were identified by NMR and
      GC/MS. tert-Butyl alcohol was identified as a minor product of the
      biotransformation of MTBE and ETBE. In addition, small amounts of a tert-butyl
      alcohol conjugate, likely a glucuronide, were present in the urine of the treated
      animals. Moreover, the mass spectra obtained indicate the presence of small
      amounts of [13C]acetone in the urine of [13C]MTBE and [13C]ETBE-treated rats. 2
      Methyl-1,2-propanediol, 2-hydroxyisobutyrate, and another unidentified conjugate
      of tert-butyl alcohol, most probably a sulfate, were major urinary metabolites of
      MTBE and ETBE as judged by the intensities of the NMR signals. In [13C]-tert
      butyl alcohol-dosed rats, [13C]acetone, tert-butyl alcohol, and its glucuronide
      represented minor metabolites; as with the ethers, 2-methyl-1,2-propanediol, 2
      hydroxyisobutyrate, and the presumed tert-butyl alcohol sulfate were the major
      metabolites present. In one human individual given 5 mg/kg [13C]-tert-butyl
      alcohol orally, 2-methyl-1,2-propanediol and 2-hydroxyisobutyrate were major
      metabolites in urine detected by 13C NMR analysis. Unconjugated tert-butyl
      alcohol and tert-butyl alcohol glucuronide were present as minor metabolites, and
      traces of the presumed tert-butyl alcohol sulfate were also present. Our results
      suggest that tert-butyl alcohol formed from MTBE and ETBE is intensively
      metabolized by further oxidation reactions. Studies to elucidate mechanisms of
      toxicity for these ethers to the kidney need to consider potential toxicities
      induced by these metabolites.

PMID- 9625734
TI  - Roles of cytochromes P450 1A2 and 3A4 in the oxidation of estradiol and estrone
      in human liver microsomes.
AB  - Of seven cDNA-expressed human cytochrome P450 (P450) enzymes (P450s 1A2, 2B6,
      2C9, 2C19, 2D6, 2E1, and 3A4) examined, P450 1A2 was the most active in
      catalyzing 2- and 4-hydroxylations of estradiol and estrone. P450 3A4 and P450
      2C9 also catalyzed these reactions although to lesser extents than P450 1A2. P450
      1A2 also efficiently oxidized estradiol at the 16alpha-position but was less
      active in estrone 16alpha-hydroxylation; the latter reaction and also estradiol
      16alpha-hydroxylation were catalyzed by P450 3A4 at significant levels. Anti-P450
      1A2 antibodies inhibited 2- and 4-hydroxylations of these two estrogens catalyzed
      by liver microsomes of some of the human samples examined. Estradiol 16alpha
      hydroxylation was inhibited by both anti-P450 1A2 and anti-P450 3A4, while
      estrone 16alpha-hydroxylation was significantly suppressed by anti-P450 3A4 in
      human liver microsomes. Fluvoxamine efficiently inhibited the estrogen
      hydroxylations in human liver samples that contained high levels of P450 1A2,
      while ketoconazole affected these activities in human samples in which P450 3A4
      levels were high. alpha-Naphthoflavone either stimulated or had no effect on
      estradiol hydroxylation catalyzed by liver microsomes; the intensity of this
      effect depended on the human samples and their P450s. Interestingly, in the
      presence of anti-P450 3A4 antibodies, alpha-naphthoflavone was found to be able
      to inhibit estradiol and estrone 2-hydroxylations catalyzed by human liver
      microsomes. The results suggest that both P450s 1A2 and 3A4 have major roles in
      oxidations of estradiol and estrone in human liver and that the contents of these
      two P450 forms in liver microsomes determine which P450 enzymes are most
      important in hepatic estrogen hydroxylation by individual humans. P450 3A4 may be
      expected to play a more important role for some of the estrogen hydroxylation
      reactions than P450 1A2. Knowledge of roles of individual P450s in these estrogen
      hydroxylations has relevance to current controversies in hormonal carcinogenesis
      [Service, R. F. (1998) Science 279, 1631-1633].

PMID- 9625735
TI  - Replication inhibition and miscoding properties of DNA templates containing a
      site-specific cis-thymine glycol or urea residue.
AB  - Oligodeoxynucleotides modified site-specifically with cis-thymine glycol or urea
      residue, two ionizing radiation/oxidation damages, were used as templates in
      primer extension reactions catalyzed by 3' --> 5' exonuclease-deficient Klenow
      fragment, human DNA polymerase beta, AMV reverse transcriptase, and a modified T7
      DNA polymerase (Sequenase). Both lesions blocked DNA replication one nucleotide
      before and opposite the lesion site, but a significant fraction of full-length
      product was obtained after prolonged incubation. Hill plot analysis of the
      results on both thymine glycol- and urea- containing templates by 3' --> 5'
      exonuclease-deficient Klenow fragment for incorporation of either dATP or dGTP
      gave linear plots with Hill coefficients much less than 1. This suggests that the
      dNTP concentration influences the termination of DNA synthesis at multiple steps
      of the catalytic process. The specificity of nucleotide incorporation opposite
      these lesions and chain extension by the same polymerase was determined by a
      steady-state kinetic analysis. The kinetic studies established that the rate of
      nucleotide incorporation and chain extension was highest with deoxyadenosine
      opposite both these lesions. However, the efficiency of forming a G.T pair
      relative to an A.T pair for the control at a level of 1/10(9) was enhanced to
      approximately 1/160 for thymine glycol and 1/20 for urea, although the former
      lesion was more bypassable than the latter lesion. On the basis of these in vitro
      results, we conclude that both these DNA damages are impediments of DNA synthesis
      and that a urea residue, in particular, has the potential to miscode.

PMID- 9625736
TI  - Structure, conformations, and repair of DNA adducts from dibenzo[a, l]pyrene: 32P
      postlabeling and fluorescence studies.
AB  - The nature of stable DNA adducts derived from the very potent carcinogen
      dibenzo[a,l]pyrene (DB[a,l]P) in the presence of rat liver microsomes in vitro
      and in mouse skin in vivo has been studied using 32P-postlabeling and laser-based
      fluorescence techniques. Analysis of DB[a,l]P-DNA adducts via 32P-postlabeling
      has been obtained by comparison of the adduct patterns to those obtained from
      reactions of synthetic (+/-)-anti-, (+)-anti-, (-)-anti-, and (+/-)-syn-DB[a,l]P
      11,12-diol 13,14-epoxide (DB[a,l]PDE) with single nucleotides and calf thymus
      DNA. anti-DB[a,l]PDE-dA adducts derived from the (-)-enantiomer are the major
      adducts formed in calf thymus DNA and in mouse skin DNA. The ratio of
      deoxyadenosine to deoxyguanosine modification is approximately 2:1 in mouse skin
      exposed to DB[a,l]P; activation by rat liver microsomes leads to a similar
      profile of adducts but with two additional spots. The conformations of DB[a,l]P
      adducts in native DNA, as well as the possibility of conformation-dependent
      repair, have been explored by low-temperature fluorescence spectroscopy. These
      studies have been performed using polynucleotides and calf thymus DNA reacted in
      vitro with DB[a,l]PDE and native DNA from mouse epidermis exposed to DB[a, l]P.
      The results show that adducts are heterogeneous, possess different structures,
      and adopt different conformations. External, external but base-stacked and
      intercalated adduct conformations are observed in calf thymus DNA and in mouse
      skin DNA samples. Differences in adduct repair rates are also revealed; namely,
      the analysis of mouse skin DNA samples obtained at 24 and 48 h after exposure to
      DB[a,l]P clearly shows that external adducts are repaired more efficiently than
      intercalated adducts. These results, taken together with those for B[a]P-DNA
      adducts [Suh et al. (1995) Carcinogenesis 16, 2561-2569], indicate that the
      repair of DNA damage resulting from PAH diol epoxides is conformation-dependent.

PMID- 9625738
TI  - Effect of ionic state of 2'-deoxyguanosine and solvent on its aralkylation by
      benzyl bromide.
AB  - To extend studies of the aralkylation of nucleic acid components under a variety
      of solvent conditions, we determined product distributions from the reactions of
      benzyl bromide with 2'-deoxyguanosine and the anion of 2'-deoxyguanosine in 2,2,
      2-trifluoroethanol (TFE) and compared these distributions with those from the
      reaction of the anion with benzyl bromide in N, N-dimethylacetamide (DMA). 7
      Benzylguanine was the only benzylated product detected in the reaction with the
      neutral nucleoside in TFE. In striking contrast, the reaction of the anion of 2'
      deoxyguanosine with benzyl bromide in TFE produced N2-benzyl-2'-deoxyguanosine in
      significant yield and with high selectivity. The reaction of the anion of 2'
      deoxyguanosine with benzyl bromide in DMA produced products derived only from
      reaction at the 1- and/or 7-position of the nucleoside. The weakly nucleophilic
      but protic polar solvent TFE and the iminolate tautomeric form of the 2'
      deoxyguanosine anion appear to be essential for benzylation at the exocyclic N2
      position.

PMID- 9625737
TI  - Stable expression of human cytochrome P450 1B1 in V79 Chinese hamster cells and
      metabolically catalyzed DNA adduct formation of dibenzo[a,l]pyrene.
AB  - Chinese hamster V79 cell lines were constructed for stable expression of human
      cytochrome P450 1B1 (P450 1B1) in order to study its role in the metabolic
      activation of chemicals and toxicological consequences. The new V79 cell lines
      were applied to studies on DNA adduct formation of the polycyclic aromatic
      hydrocarbon (PAH) dibenzo[a,l]pyrene (DB[a,l]P). This compound has been found to
      be an environmental pollutant, and in rodent bioassays it is the most
      carcinogenic PAH yet discovered. Activation of DB[a,l]P in various metabolizing
      systems occurs via fjord region DB[a,l]P-11, 12-dihydrodiol 13,14-epoxides
      (DB[a,l]PDE): we found that DB[a,l]P is stereoselectively metabolized in human
      mammary carcinoma MCF-7 cells to the (-)-anti- and (+)-syn-DB[a,l]PDE which both
      bind extensively to cellular DNA. To follow up this study and to relate specific
      DNA adducts to activation by individual P450 isoforms, the newly established V79
      cells stably expressing human P450 1B1 were compared with those expressing human
      P450 1A1. DNA adduct formation in both V79 cell lines differed distinctively
      after incubation with DB[a,l]P or its enantiomeric 11,12-dihydrodiols. Human P450
      1A1 catalyzed the formation of DB[a,l]PDE-DNA adducts as well as several highly
      polar DNA adducts as yet unidentified. The proportion of these highly polar
      adducts to DB[a,l]PDE adducts was dependent upon both the concentration of
      DB[a,l]P and the time of exposure. In contrast, V79 cells stably expressing human
      P450 1B1 generated exclusively DB[a,l]PDE-DNA adducts. Differences in the total
      level of DNA binding were also observed. Exposure to 0.1 microM DB[a,l]P for 6 h
      caused a significantly higher level of DNA adducts in V79 cells stably expressing
      human P450 1B1 (370 pmol/mg of DNA) compared to those with human P450 1A1 (35
      pmol/mg of DNA). A 4-fold higher extent of DNA binding was catalyzed by human
      P450 1B1 (506 pmol/mg of DNA) compared to human P450 1A1 (130 pmol/mg of DNA) 6 h
      after treatment with 0.05 microM (-)-(11R,12R)-dihydrodiol. In cells stably
      expressing human P450 1B1 the DNA adducts were derived exclusively from the (-)
      anti-DB[a,l]PDE. These results indicate that human P450 1B1 and P450 1A1 differ
      in their regio- and stereochemical selectivity of activation of DB[a,l]P with
      P450 1B1 forming a higher proportion of the highly carcinogenic (-)-anti-(11R,
      12S,13S,14R)-DB[a,l]PDE metabolite.

PMID- 9625739
TI  - A simple alternate substrate test can help determine the aqueous or bilayer
      location of binding sites for hydrophobic ligands/substrates on membrane
      proteins.
AB  - It is of general interest to determine the location of binding sites in membrane
      protein receptors and enzymes. A simple method is described that relies on the
      use of alternate substrates with defined hydrophobicity and decipherable trends
      in relative kcat/Km values. The rates at first-order conditions (low substrate
      concentrations) for at least two substrates are determined at a defined
      lipid/detergent volume fraction. Ratios of the rates (which at first-order
      conditions are linearly related to substrate concentration) are compared to the
      predicted partitioning of the substrates. Since the relative rates depend also on
      the kcat/Km ratios, the contribution of this parameter and its limits is
      discussed. When alternate substrates that fulfill reasonable criteria regarding
      kcat/Km values are used, the location of binding sites can be tentatively
      predicted. Examples are given describing evaluation of the location of the
      xenobiotic binding site in detoxication enzymes (microsomal glutathione
      transferase and cytochrome P450). Furthermore, it is argued that unspecific
      binding sites for hydrophobic molecules, such as those that are important in many
      detoxication enzymes, can only benefit from hydrophobic interactions facing the
      aqueous compartment of the cell. The membrane location of many drug-metabolizing
      enzymes thus implies that an aqueous active site located close to the membrane is
      advantageous, an advantage that could be realized if a concentration gradient of
      hydrophobic molecules extends into the aqueous phase at lipid interfaces.

PMID- 9625740
TI  - Novel features of intermediate filament dynamics revealed by green fluorescent
      protein chimeras.
AB  - In order to study the dynamic behavior of intermediate filament networks in
      living cells, we have prepared constructs fusing green fluorescent protein to
      intermediate filament proteins. Vimentin fused to green fluorescent protein
      labeled the endogenous intermediate filament network. We generated stable SW13
      and NIH3T3 cell lines that express an enhanced green fluorescent protein fused to
      the N-terminus of full-length vimentin. We were able to observe the dynamic
      behavior of the intermediate filament network in these cells for periods as long
      as 4 hours (images acquired every 2 minutes). In both cell lines, the vimentin
      network constantly moves in a wavy manner. In the NIH3T3 cells, we observed
      extension of individual vimentin filaments at the edge of the cell. This movement
      is dependent on microtubules, since the addition of nocodazole stopped the
      extension of the intermediate filaments. Injection of anti-IFA causes the
      redistribution or 'collapse' of intermediate filaments. We injected anti-IFA
      antibodies into NIH3T3 cells stably expressing green fluorescent protein fused to
      vimentin and found that individual intermediate filaments move slowly towards the
      perinuclear area without obvious disassembly. These results demonstrate that
      individual intermediate filaments are translocated during the collapse, rather
      than undergoing disassembly-induced redistribution. Injections of tubulin
      antibodies disrupt the interactions between intermediate filaments and stable
      microtubules and cause the collapse of the vimentin network showing that these
      interactions play an important role in keeping the intermediate filament network
      extended. The nocodazole inhibition of intermediate filament extension and the
      anti-IFA microinjection experiments are consistent with a model in which
      intermediate filaments exhibit an extended distribution when tethered to
      microtubules, but are translocated to the perinuclear area when these connections
      are severed.

PMID- 9625742
TI  - Actin microfilaments control the MHC class II antigen presentation pathway in B
      cells.
AB  - Newly synthesised major histocompatibility complex class II molecules associate
      with invariant chains (Ii) to form nonameric complexes. These complexes are
      transported to endosomes, where proteolytic enzymes generate alphabeta class II
      dimers associated with nested Ii-derived peptides. These peptides are then
      exchanged with antigen peptide, and mature class II molecules reach the cell
      surface. The role of the actin cytoskeleton in the transport and maturation of
      class II molecules has not been studied. We show here that upon treatment with
      cytochalasin D (cyto D), the rate of Ii degradation is drastically reduced in B
      cells. Cyto D treatment also leads to a delayed appearance of stable forms of
      class II molecules, and a reduced presentation efficiency of antigen determinants
      requiring newly synthesised class II molecules. Under such conditions, we found
      that invariant chain fragments and class II molecules are accumulated in early
      and late endosomal compartments, whereas the leupeptin protease inhibitor induces
      their accumulation in lysosomal compartments. The addition of cyto D to leupeptin
      blocks the delivery of class II/invariant chain complexes to lysosomes, and
      further inhibits degradation of Ii. The dynamics of the actin cytoskeleton can
      therefore control the meeting point between newly synthesised class II molecules
      and lysosomal proteases, involved in Ii degradation and antigen peptide loading.

PMID- 9625741
TI  - Localisation and interaction of the protein components of the yeast 2 mu circle
      plasmid partitioning system suggest a mechanism for plasmid inheritance.
AB  - Replicating plasmids are highly unstable in yeast, because they are retained in
      mother cells. The 2 mu circle plasmid overcomes this maternal inheritance bias by
      using a partitioning system that involves the plasmid encoded proteins Rep1p and
      Rep2p, and the cis-acting locus STB. It is thus widely exploited as a cloning
      vehicle in yeast. However, little is known about the cellular or molecular
      mechanisms by which effective partitioning is achieved, and models of both free
      diffusion and plasmid localisation have been proposed. Here we show that Rep1p
      and Rep2p proteins interact to form homo- and hetero-complexes in vitro. In vivo,
      Rep1p and Rep2p are shown to be nuclear proteins, exhibiting sub-nuclear
      concentration in distinct foci. The number of foci appears constant regardless of
      plasmid copy number and cell ploidy level. Before cell division, the number of
      foci increases, and we observe approximately equal allocation of foci to mother
      and daughter cell nuclei. We show that whereas Rep2p expressed alone is found
      exclusively in the nucleus, Rep1p requires the presence of Rep2p for effective
      nuclear localisation. High levels of 2 mu plasmid induce a multiple-budded
      elongated cell phenotype, which we show can be phenocopied by overexpression of
      both REP1 and REP2 together but not alone. Taken together, these results suggest
      that Rep1p and Rep2p interact in vivo, and occupy defined nuclear sites that are
      allocated to both mother and daughter nuclei during division. We propose a model
      for 2 mum plasmid partitioning based on these results, involving the association
      of plasmid DNA with specific, segregated subnuclear sites.

PMID- 9625743
TI  - The sparing of extraocular muscle in dystrophinopathy is lost in mice lacking
      utrophin and dystrophin.
AB  - The extraocular muscles are one of few skeletal muscles that are structurally and
      functionally intact in Duchenne muscular dystrophy. Little is known about the
      mechanisms responsible for differential sparing or targeting of muscle groups in
      neuromuscular disease. One hypothesis is that constitutive or adaptive properties
      of the unique extraocular muscle phenotype may underlie their protection in
      dystrophinopathy. We assessed the status of extraocular muscles in the mdx mouse
      model of muscular dystrophy. Mice showed mild pathology in accessory extraocular
      muscles, but no signs of pathology were evident in the principal extraocular
      muscles at any age. By immunoblotting, the extraocular muscles of mdx mice
      exhibited increased levels of a dystrophin analog, dystrophin-related protein or
      utrophin. These data suggest, but do not provide mechanistic evidence, that
      utrophin mediates eye muscle protection. To examine a potential causal
      relationship, knockout mouse models were used to determine whether eye muscle
      sparing could be reversed. Mice lacking expression of utrophin alone, like the
      dystrophin-deficient mdx mouse, showed no pathological alterations in extraocular
      muscle. However, mice deficient in both utrophin and dystrophin exhibited severe
      changes in both the accessory and principal extraocular muscles, with the eye
      muscles affected more adversely than other skeletal muscles. Selected extraocular
      muscle fiber types still remained spared, suggesting the operation of an
      alternative mechanism for muscle sparing in these fiber types. We propose that an
      endogenous upregulation of utrophin is mechanistic in protecting extraocular
      muscle in dystrophinopathy. Moreover, data lend support to the hypothesis that
      interventions designed to increase utrophin levels may ameliorate the pathology
      in other skeletal muscles in Duchenne muscular dystrophy.

PMID- 9625744
TI  - The single CH domain of calponin is neither sufficient nor necessary for F-actin
      binding.
AB  - Calponins have been implicated in the regulation of actomyosin interactions in
      smooth muscle cells, cytoskeletal organisation in nonmuscle cells, and the
      control of neurite outgrowth. Domains homologous to the amino-terminal region of
      calponin have been identified in a variety of actin cross-linking proteins and
      signal transduction molecules, and by inference these 'calponin homology (CH)
      domains' have been assumed to participate in actin binding. We here report on the
      actin binding activities of the subdomains of the calponin molecule. All three
      mammalian isoforms of calponin (basic h1, neutral h2 and acidic) possess a single
      CH domain at their amino terminus as well as three tandem repeats proximal to the
      carboxyl terminus. Calponin h2 differs, however, from h1 in lacking a consensus
      actin-binding motif in the region 142-163, between the CH domain and the tandem
      repeats, which in h1 calponin can be chemically cross-linked to actin. Despite
      the absence of this consensus actin-binding motif, recombinant full-length h2
      calponin co-sediments in vitro with F-actin, suggesting the presence of another
      binding site in the molecule. It could be shown that this binding site resides in
      the C-terminal tandem repeats and not in the CH domain. Thus, constructs of h2
      calponin bearing partial or complete deletions of the triple repeated sequences
      failed to co-localise with actin stress fibres despite the presence of a CH
      domain. Deletion of the acidic carboxyl terminus, beyond the repeats, increased
      actin binding, suggesting that the carboxy-terminal tail may modulate actin
      association. Results obtained from transient transfections of amino- and carboxy
      terminal truncations in h1 calponin were consistent with the established location
      of the actin binding motif outside and carboxy-terminal to the CH domain, and
      confirm that the presence of a single CH domain alone is neither sufficient nor
      necessary to mediate actin binding. Instead, the carboxy-terminal tandem repeats
      of h1 and h2 calponin are shown to harbour a second, independent actin binding
      motif.

PMID- 9625745
TI  - Nuclear import of protein kinase C occurs by a mechanism distinct from the
      mechanism used by proteins with a classical nuclear localization signal.
AB  - Protein kinase C does not have any known nuclear localization signal but,
      nevertheless, is redistributed from the cytoplasm to the nucleus upon various
      stimuli. In NIH 3T3 fibroblasts stimulation with phorbol ester leads to a
      translocation of protein kinase C alpha to the plasma membrane and into the cell
      nucleus. We compared the mechanism of protein kinase C alpha's transport into the
      nucleus with the transport mechanism of a protein with a classical nuclear
      localization signal at several steps. To this end, we co-microinjected
      fluorescently labeled bovine serum albumin to which a nuclear localization signal
      peptide was coupled, together with substances interfering with conventional
      nuclear protein import. Thereafter, the distribution of both the nuclear
      localization signal-bearing reporter protein and protein kinase C alpha was
      analyzed in the same cells. We can show that, in contrast to the nuclear
      localization signal-dependent transport, the phorbol ester-induced transport of
      protein kinase C alpha is not affected by microinjection of antibodies against
      the nuclear import factor p97/importin/karyopherin beta or microinjection of non
      hydrolyzable GTP-analogs. This suggests that nuclear import of protein kinase C
      alpha is independent of p97/importin/karyopherin beta and independent of GTP. At
      the nuclear pore there are differences between the mechanisms too, since nuclear
      transport of protein kinase C alpha cannot be inhibited by wheat germ agglutinin
      or an antibody against nuclear pore complex proteins. Together these findings
      demonstrate that the nuclear import of protein kinase C alpha occurs by a
      mechanism distinct from the one used by classical nuclear localization signal
      bearing proteins at several stages.

PMID- 9625746
TI  - Actomyosin motor in the merozoite of the malaria parasite, Plasmodium falciparum:
      implications for red cell invasion.
AB  - The genome of the malaria parasite, Plasmodium falciparum, contains a myosin gene
      sequence, which bears a close homology to one of the myosin genes found in
      another apicomplexan parasite, Toxoplasma gondii. A polyclonal antibody was
      generated against an expressed polypeptide of molecular mass 27,000, based on
      part of the deduced sequence of this myosin. The antibody reacted with the
      cognate antigen and with a component of the total parasite protein on
      immunoblots, but not with vertebrate striated or smooth muscle myosins. It did,
      however, recognise two components in the cellular protein of Toxoplasma gondii.
      The antibody was used to investigate stage-specificity of expression of the
      myosin (here designated Pf-myo1) in P. falciparum. The results showed that the
      protein is synthesised in mature schizonts and is present in merozoites, but
      vanishes after the parasite enters the red cell. Pf-myo1 was found to be largely,
      though not entirely, associated with the particulate parasite cell fraction and
      is thus presumably mainly membrane bound. It was not solubilised by media that
      would be expected to dissociate actomyosin or myosin filaments, or by non-ionic
      detergent. Immunofluorescence revealed that in the merozoite and mature schizont
      Pf-myo1 is predominantly located around the periphery of the cell. Immuno-gold
      electron microscopy also showed the presence of the myosin around almost the
      entire parasite periphery, and especially in the region surrounding the apical
      prominence. Labelling was concentrated under the plasma membrane but was not seen
      in the apical prominence itself. This suggests that Pf-myo1 is associated with
      the plasma membrane or with the outer membrane of the subplasmalemmal cisterna,
      which forms a lining to the plasma membrane, with a gap at the apical prominence.
      The results lead to a conjectural model of the invasion mechanism.

PMID- 9625747
TI  - A novel taxol-induced vimentin phosphorylation and stabilization revealed by
      studies on stable microtubules and vimentin intermediate filaments.
AB  - To understand how protein phosphorylation modulates cytoskeletal organization, we
      used immunofluorescence microscopy to examine the effects of okadaic acid, a
      serine/threonine protein phosphatase inhibitor, and taxol, a microtubule
      stabilizing agent, on stable (acetylated and detyrosinated) microtubules,
      vimentin intermediate filaments and other cytoskeletal elements in CV-1 cells.
      Okadaic acid caused major changes in both stable microtubules and vimentin
      intermediate filaments, but through independent mechanisms. At 300 nM, okadaic
      acid caused apparent fragmentation and loss of stable microtubules which was not
      prevented by prior exposure to K252a. In contrast, major reorganization of
      vimentin intermediate filaments elicited at 750 nM okadaic acid was prevented by
      prior exposure to K252a. Taxol pretreatment blocked the effects of okadaic acid
      on stable microtubules and vimentin intermediate filaments. Recent reports have
      revealed that taxol can activate cellular signal transduction pathways in
      addition to its known ability to promote microtubule stabilization, so the
      possibility that taxol-induced resistance of vimentin intermediate filaments to
      okadaic acid was through a microtubule-independent mechanism involving direct
      phosphorylation of intermediate filament proteins was explored. Vimentin
      immunoprecipitation from cytoskeletal extracts from 32P-labeled cells revealed
      that taxol (4 microM, 1 or 2 hours) caused about a 2-fold increase in vimentin
      phosphorylation. This phosphorylation was recovered exclusively in cytoskeletal
      vimentin, in contrast to the increased phosphorylation of soluble and
      cytoskeletal vimentin caused by exposure to 750 nM okadaic acid. Phosphorylation
      of soluble and cytoskeletal vimentin from cells exposed to taxol (4 microM, 1
      hour) then okadaic acid (750 nM, 1 hour) was comparable to taxol-treatment alone.
      These findings demonstrate a novel new activity of taxol, induction of vimentin
      phosphorylation, that may impact on vimentin organization and stability.

PMID- 9625748
TI  - Vascular endothelial growth factor induces VE-cadherin tyrosine phosphorylation
      in endothelial cells.
AB  - Interendothelial junctions play an important role in the regulation of
      endothelial functions, such as vasculogenesis, angiogenesis, and vascular
      permeability. In this paper we show that vascular endothelial growth factor
      (VEGF), a potent inducer of new blood vessels and vascular permeability in vivo,
      stimulated the migration of endothelial cells after artificial monolayer wounding
      and induced an increase in paracellular permeability of human umbilical vein
      endothelial cells (HUVECs). Furthermore, VEGF increased phosphotyrosine labeling
      at cell-cell contacts. Biochemical analyses revealed a strong induction of VEGF
      receptor-2 (flk-1/KDR) tyrosine-autophosphorylation by VEGF which was maximal
      after 5 minutes and was followed by receptor downregulation. 15 minutes to 1 hour
      after VEGF stimulation the endothelial adherens junction components VE-cadherin,
      beta-catenin, plakoglobin, and p120 were maximally phosphorylated on tyrosine,
      while alpha-catenin was not modified. PECAM-1/CD31, another cell-cell junctional
      adhesive molecule, was tyrosine phosphorylated with similar kinetics in response
      to VEGF. In contrast, activation of VEGF-receptor-1 (Flt-1) by its specific
      ligand placenta growth factor (PlGF) had no effect on the tyrosine
      phosphorylation of cadherins and catenins. Despite the rapid and transient
      receptor activation and the subsequent tyrosine phosphorylation of adherens
      junction proteins the cadherin complex remained stable and associated with
      junctions. Our results demonstrate that the endothelial adherens junction is a
      downstream target of VEGFR-2 signaling and suggest that tyrosine phosphorylation
      of its components may be involved in the the loosening of cell-cell contacts in
      established vessels to modulate transendothelial permeability and to allow
      sprouting and cell migration during angiogenesis.

PMID- 9625749
TI  - High proliferative potential-quiescent cells: a working model to study primitive
      quiescent hematopoietic cells.
AB  - Human adult hematopoietic stem cells are mostly quiescent or slow cycling. We
      have previously demonstrated that blocking of transforming growth factor-beta1
      (TGF-beta1) is able to activate, in the presence of cytokines, primitive
      quiescent hematopoietic multipotent progenitors which could not grow in a two
      week semi-solid culture assay (short term culture). We have also shown that anti
      TGF-beta1 can up-modulate c-KIT, the receptor of the stem cell factor (steel
      factor). To elucidate whether TGF-beta1 plays a central role in controlling the
      quiescence of hematopoietic primitive cells, it was necessary to demonstrate, as
      detailed in this study, that: (1) whatever the cytokine combination tested,
      addition of anti-TGF-beta1 releases from quiescence multipotent progenitors with
      a significantly higher hematopoietic potential than those activated by cytokines
      alone. (2) Other important cytokine receptors controlling the most primitive
      hematopoietic cells such as FLT3 and the IL6 receptor (IL6-R) are down-modulated
      by TGF-beta1 but rapidly up-modulated by anti-TGF-beta1. (3) Anti-TGF-beta1
      sensitive multipotent and high proliferative potential progenitors express these
      cytokine receptors at a low level (FLT3(low) and IL6-Rlow). According to these
      results, we propose the working model of 'High Proliferative Potential-Quiescent
      cells' to refer to these primitive hematopoietic multipotent progenitors that are
      highly sensitive to the growth inhibitory effect of TGF-beta1. This model could
      be valid not only to study the human hematopoietic quiescent progenitors but also
      for other somatic stem cell systems.

PMID- 9625750
TI  - Three distinct steps in transport of vesicular stomatitis virus glycoprotein from
      the ER to the cell surface in vivo with differential sensitivities to GTP gamma
      S.
AB  - Microinjected GTP gamma S revealed three distinct steps in the exocytic transport
      of the temperature sensitive glycoprotein of vesicular stomatitis virus (ts-O45
      G) from the ER to the cell surface in intact Vero cells. While COPII dependent
      export of ts-O45-G from the ER is blocked in cells injected with recombinant
      protein of a dominant mutant of SAR1a (SAR1a[H79G]) inhibited in GTP hydrolysis,
      neither injected GTP gamma S nor antibodies against beta-COP (anti-EAGE)
      interfere with this transport step significantly. In contrast, transport to the
      Golgi complex is blocked by 50 microM GTP gamma S, a dominant mutant of ARF1
      (ARF1[Q71L]) inhibited in GTP hydrolysis, or microinjected anti-EAGE, but
      injected Sar1a[H79G]p has no effect. Microinjection of GTP gamma S or expression
      of ARF[Q71L] rapidly induces accumulation of COPI coated vesicular structures
      lacking ts-O45-G. Finally, transport of ts-O45-G from the trans-Golgi network
      (TGN) to the cell surface is inhibited only by high concentrations of GTP gamma S
      (500 microM). Interestingly, this step is only partially brefeldin A sensitive,
      and injected antibodies against beta-COP and p200/myosin II, a TGN membrane
      associated protein, have no effect. These data provide first strong in vivo
      evidence for at least three distinct steps in the exocytic pathway of mammalian
      cells regulated by different sets of GTPases and coat proteins. COPII, but not
      COPI, is required for ER export of ts-O45-G. COPI plays a role in subsequent
      transport to the Golgi complex, and a so far unidentified GTP gamma S sensitive
      coat appears to be involved in transport from the TGN to the cell surface.

PMID- 9625751
TI  - The nuclear import factor p10 regulates the functional size of the nuclear pore
      complex during oogenesis.
AB  - Previtellogenic, stage-1 Xenopus oocytes produce mainly 5S and tRNA, whereas
      vitellogenic oocytes, stages 2-6, synthesize predominantly 18S and 28S rRNA.
      Using nucleoplasmin-coated gold as a transport substrate, it was determined that
      the shift in synthesis from small to large RNAs during oogenesis is accompanied
      by an increase in both the rates of signal-mediated nuclear import and the
      functional size of nuclear pores. It was observed that, despite the reduction in
      transport capacity, gold still accumulated at the cytoplasmic surface of the
      pores in stage-1 oocytes. This suggested that transport in these cells is limited
      by translocation factors, rather than by cytoplasmic binding factors. Analysis of
      extracts prepared from stage-1 and vitellogenic oocytes revealed that the
      transport factor p10 is more abundant in stage-1 cells. Microinjection of
      purified p10 into stage-2 oocytes reduced the nuclear import of large gold
      particles to the level observed in stage-1 cells. It is concluded that p10 can
      modulate transport through the pores by regulating the functional size of the
      central transporter element.

PMID- 9625752
TI  - Impaired mechanical stability, migration and contractile capacity in vimentin
      deficient fibroblasts.
AB  - Loss of a vimentin network due to gene disruption created viable mice that did
      not differ overtly from wild-type littermates. Here, primary fibroblasts derived
      from vimentin-deficient (-/-) and wild-type (+/+) mouse embryos were cultured,
      and biological functions were studied in in vitro systems resembling stress
      situations. Stiffness of -/- fibroblasts was reduced by 40% in comparison to wild
      type cells. Vimentin-deficient cells also displayed reduced mechanical stability,
      motility and directional migration towards different chemo-attractive stimuli.
      Reorganization of collagen fibrils and contraction of collagen lattices were
      severely impaired. The spatial organization of focal contact proteins, as well as
      actin microfilament organization was disturbed. Thus, absence of a vimentin
      filament network does not impair basic cellular functions needed for growth in
      culture, but cells are mechanically less stable, and we propose that therefore
      they are impaired in all functions depending upon mechanical stability.

PMID- 9625753
TI  - Patterns for RANTES secretion and intercellular adhesion molecule 1 expression
      mediate transepithelial T cell traffic based on analyses in vitro and in vivo.
AB  - Immune cell migration into and through mucosal barrier sites in general and
      airway sites in particular is a critical feature of immune and inflammatory
      responses, but the determinants of transepithelial (unlike transendothelial)
      immune cell traffic are poorly defined. Accordingly, we used primary culture
      airway epithelial cells and peripheral blood mononuclear cells to develop a cell
      monolayer system that allows for apical-to-basal and basal-to-apical T cell
      transmigration that can be monitored with quantitative immunofluorescence flow
      cytometry. In this system, T cell adhesion and subsequent transmigration were
      blocked in both directions by monoclonal antibodies (mAbs) against lymphocyte
      function-associated antigen 1 (LFA-1) or intercellular adhesion molecule 1 (ICAM
      1) (induced by interferon gamma [IFN-gamma] treatment of epithelial cells). The
      total number of adherent plus transmigrated T cells was also similar in both
      directions, and this pattern fit with uniform presentation of ICAM-1 along the
      apical and basolateral cell surfaces. However, the relative number of
      transmigrated to adherent T cells (i.e., the efficiency of transmigration) was
      increased in the basal-to-apical relative to the apical-to-basal direction, so an
      additional mechanism was needed to mediate directional movement towards the
      apical surface. Screening for epithelial-derived beta-chemokines indicated that
      IFN-gamma treatment caused selective expression of RANTES (regulated upon
      activation, normal T cell expressed and secreted), and the functional
      significance of this finding was demonstrated by inhibition of epithelial-T cell
      adhesion and transepithelial migration by anti-RANTES mAbs. In addition, we found
      that epithelial (but not endothelial) cells preferentially secreted RANTES
      through the apical cell surface thereby establishing a chemical gradient for
      chemotaxis across the epithelium to a site where they may be retained by high
      levels of RANTES and apical ICAM-1. These patterns for epithelial presentation of
      ICAM-1 and secretion of RANTES appear preserved in airway epithelial tissue
      studied either ex vivo with expression induced by IFN-gamma treatment or in vivo
      with endogenous expression induced by inflammatory disease (i.e., asthma). Taken
      together, the results define how the patterns for uniform presentation of ICAM-1
      along the cell surface and specific apical sorting of RANTES may serve to mediate
      the level and directionality of T cell traffic through epithelium (distinct from
      endothelium) and provide a basis for how this process is precisely coordinated to
      route immune cells to the mucosal surface and maintain them there under normal
      and stimulated conditions.

PMID- 9625754
TI  - Lung epithelial cells are a major site of murine gammaherpesvirus persistence.
AB  - It is currently believed that latently infected, resting B lymphocytes are
      central to gammaherpesvirus persistence, whereas mucosal epithelial cells are
      considered nonessential. We have readdressed the question of nonlymphoid
      persistence using murine gammaherpesvirus 68 (MHV-68). To dissect lymphoid from
      nonlymphoid persistence, we used microMT transgenic mice that are defective in B
      cells. MHV-68 DNA persisted in the lungs of intact and B cell-deficient mice.
      Both episomal and linear forms of the virus genome were present in lungs,
      implying the presence of both latency and productive replication. In situ
      hybridization for virus tRNA transcripts revealed latent MHV-68 in pulmonary
      epithelial cells. Infectious virus was recovered from the lungs of microMT mice
      after T cell depletion, showing that the persisting virus DNA was reactivatable.
      Finally, using adoptive transfer of B cells into B cell-deficient mice, it was
      shown that virus persisting in lungs seeded splenic B cells, and virus resident
      in the spleen seeded the lungs. These results show that mucosal epithelia can act
      as a nonlymphoid reservoir for gammaherpesvirus persistence, and that there is a
      two-way movement of virus between lymphoid and nonlymphoid compartments during
      persistence.

PMID- 9625755
TI  - L1 antibodies block lymph node fibroblastic reticular matrix remodeling in vivo.
AB  - L1 is an immunoglobulin superfamily adhesion molecule highly expressed on neurons
      and involved in cell motility, neurite outgrowth, axon fasciculation,
      myelination, and synaptic plasticity. L1 is also expressed by nonneural cells,
      but its function outside of the nervous system has not been studied extensively.
      We find that administration of an L1 monoclonal antibody in vivo disrupts the
      normal remodeling of lymph node reticular matrix during an immune response.
      Ultrastructural examination reveals that reticular fibroblasts in mice treated
      with L1 monoclonal antibodies fail to spread and envelop collagen fibers with
      their cellular processes. The induced defect in the remodeling of the
      fibroblastic reticular system results in the loss of normal nodal architecture,
      collapsed cortical sinusoids, and macrophage accumulation in malformed sinuses.
      Surprisingly, such profound architectural abnormalities have no detectable
      effects on the primary immune response to protein antigens.

PMID- 9625756
TI  - Identification of podocalyxin-like protein as a high endothelial venule ligand
      for L-selectin: parallels to CD34.
AB  - The leukocyte adhesion molecule, L-selectin, mediates the recruitment of
      lymphocytes to secondary lymphoid organs via interactions with specific ligands
      presented on high endothelial venules (HEV). Although the HEV-derived ligands for
      L-selectin are still incompletely defined, they share a common sialomucin-like
      structure which is thought to present clustered oligosaccharides to the lectin
      domain of L-selectin. Podocalyxin-like protein (PCLP) is a transmembrane
      sialomucin that is similar in structure to the well-characterized L-selectin
      ligand CD34. PCLP has been shown previously to be expressed on the foot processes
      of podocytes in the kidney glomerulus as well as on vascular endothelium at some
      sites. We have determined that PCLP is present on HEV, where it binds to both
      recombinant L-selectin and the HEV-specific monoclonal antibody MECA-79.
      Furthermore, purified HEV-derived PCLP is able to support the tethering and
      rolling of lymphocytes under physiological flow conditions in vitro. These
      results suggest a novel function for PCLP as an adhesion molecule and allow the
      definition of conserved structural features in PCLP and CD34, which may be
      important for L-selectin ligand function.

PMID- 9625757
TI  - A role for tumor necrosis factor receptor type 1 in gut-associated lymphoid
      tissue development: genetic evidence of synergism with lymphotoxin beta.
AB  - Lymphotoxin alpha (LTalpha) signals via tumor necrosis factor receptors (TNFRs)
      as a homotrimer and via lymphotoxin beta receptor (LTbetaR) as a heterotrimeric
      LTalpha1beta2 complex. LTalpha-deficient mice lack all lymph nodes (LNs) and
      Peyer's patches (PPs), and yet LTbeta-deficient mice and TNFR-deficient mice have
      cervical and mesenteric LN. We now show that mice made deficient in both LTbeta
      and TNFR type 1 (TNFR1) lack all LNs, revealing redundancy or synergism between
      TNFR1 and LTbeta, acting presumably via LTbetaR. A complete lack of only PPs in
      mice heterozygous for both ltalpha and ltbeta, but not ltalpha or ltbeta alone,
      suggests a similar two-ligand phenomenon in PP development and may explain the
      incomplete lack of PPs seen in tnfr1-/- mice.

PMID- 9625758
TI  - The role of lymphocyte subsets in accelerated diabetes in nonobese diabetic-rat
      insulin promoter-B7-1 (NOD-RIP-B7-1) mice.
AB  - B7-1 transgene expression on the pancreatic islets in nonobese diabetic (NOD)
      mice leads to accelerated diabetes, with >50% of animals developing diabetes
      before 12 wk of age. The expression of B7-1 directly on the pancreatic beta
      cells, which do not normally express costimulator molecules, converts the cells
      into effective antigen-presenting cells leading to an intensified autoimmune
      attack. The pancreatic islet infiltrate in diabetic mice consists of CD8 T cells,
      CD4 T cells, and B cells, similar to diabetic nontransgenic NOD mice. To
      elucidate the relative importance of each of the subsets of cells, the NOD-rat
      insulin promoter (RIP)-B7-1 animals were crossed with NOD.beta2microglobulin -/-
      mice which lack major histocompatibility complex class I molecules and are
      deficient in peripheral CD8 T cells, NOD.CD4 -/- mice which lack T cells
      expressing CD4, and NOD.muMT -/- mice which lack B220-positive B cells. These
      experiments showed that both CD4 and CD8 T cells were necessary for the
      accelerated onset of diabetes, but that B cells, which are needed for diabetes to
      occur in normal NOD mice, are not required. It is possible that B lymphocytes
      play an important role in the provision of costimulation in NOD mice which is
      unnecessary in the NOD-RIP-B7-1 transgenic mice.

PMID- 9625759
TI  - Expression of constitutively active Raf-1 in the mitochondria restores
      antiapoptotic and leukemogenic potential of a transformation-deficient BCR/ABL
      mutant.
AB  - The oncogenic BCR/ABL protein protects hematopoietic cells from apoptosis induced
      by growth factor deprivation, but the mechanisms are only partially understood. A
      BCR/ABL mutant lacking amino acids 176-426 in the BCR domain (p185DeltaBCR)
      failed to protect interleukin 3-deprived 32Dcl3 myeloid precursor cells from
      apoptosis, although it possessed tyrosine kinase activity and was capable of
      activating the Ras-Raf-MAP kinase pathway. Compared to p185 wild-type
      transfectants, p185DeltaBCR-transfected cells showed markedly reduced levels of
      Bcl-2 and expressed the hypophosphorylated, proapoptotic form of BAD. Bcl-2
      expression in the mitochondrial fraction of p185DeltaBCR cells was also markedly
      diminished and mitochondrial RAF was undetectable. In p185DeltaBCR cells
      transfected with a mitochondria-targeted, constitutively active RAF (M-Raf) BAD
      was expressed in the hyperphosphorylated form and released from the mitochondria
      into the cytosol. p185DeltaBCR/M-Raf-transfected cells were completely resistant
      to apoptosis induced by growth factor deprivation in vitro. Moreover,
      constitutive expression of dominant-negative M-Raf (K375W) enhanced the
      susceptibility of 32Dcl3 cells expressing wild-type BCR/ABL to apoptosis. In
      severe combined immunodeficiency (SCID) mice, p185DeltaBCR/M-Raf double
      transfectants were leukemogenic, whereas cells expressing only p185DeltaBCR
      showed no leukemogenic potential. Together, these data support the existence of a
      BCR/ABL-dependent pathway that leads to expression of an active RAF in the
      mitochondria and promotes antiapoptotic and leukemia-inducing effects of BCR/ABL.

PMID- 9625760
TI  - Interferon-inducible T cell alpha chemoattractant (I-TAC): a novel non-ELR CXC
      chemokine with potent activity on activated T cells through selective high
      affinity binding to CXCR3.
AB  - Chemokines are essential mediators of normal leukocyte trafficking as well as of
      leukocyte recruitment during inflammation. We describe here a novel non-ELR CXC
      chemokine identified through sequence analysis of cDNAs derived from cytokine
      activated primary human astrocytes. This novel chemokine, referred to as I-TAC
      (interferon-inducible T cell alpha chemoattractant), is regulated by interferon
      (IFN) and has potent chemoattractant activity for interleukin (IL)-2-activated T
      cells, but not for freshly isolated unstimulated T cells, neutrophils, or
      monocytes. I-TAC interacts selectively with CXCR3, which is the receptor for two
      other IFN-inducible chemokines, the IFN-gamma-inducible 10-kD protein (IP-10) and
      IFN-gamma- induced human monokine (HuMig), but with a significantly higher
      affinity. In addition, higher potency and efficacy of I-TAC over IP-10 and HuMig
      is demonstrated by transient mobilization of intracellular calcium as well as
      chemotactic migration in both activated T cells and transfected cell lines
      expressing CXCR3. Stimulation of astrocytes with IFN-gamma and IL-1 together
      results in an approximately 400,000-fold increase in I-TAC mRNA expression,
      whereas stimulating monocytes with either of the cytokines alone or in
      combination results in only a 100-fold increase in the level of I-TAC transcript.
      Moderate expression is also observed in pancreas, lung, thymus, and spleen. The
      high level of expression in IFN- and IL-1-stimulated astrocytes suggests that I
      TAC could be a major chemoattractant for effector T cells involved in the
      pathophysiology of neuroinflammatory disorders, although I-TAC may also play a
      role in the migration of activated T cells during IFN-dominated immune responses.

PMID- 9625761
TI  - Interferon enhances tumor necrosis factor-induced vascular cell adhesion molecule
      1 (CD106) expression in human endothelial cells by an interferon-related factor 1
      dependent pathway.
AB  - Tumor necrosis factor (TNF) and interleukin 1 are known to initiate endothelial
      vascular cell adhesion molecule (VCAM)-1 transcription primarily by activating
      nuclear factor (NF)-kappaB, which translocates to the nucleus. In addition to two
      NF-kappaB elements found within the minimal cytokine-inducible VCAM-1 promoter,
      an interferon-related factor (IRF) element (IRF-1) has been identified close to
      the transcription initiation site, suggesting that cytokines that induce IRF-1
      might affect VCAM-1 expression levels. We therefore investigated the effects of
      interferons (IFNs), which strongly induce IRF-1, on VCAM-1 transcription and
      expression. We show that IFN-alpha and -gamma enhance TNF-induced VCAM-1 mRNA
      transcription and protein expression in human endothelial cells. IFN enhancement
      of TNF-induced expression is also seen using chloramphenicol acetyl transferase
      reporter genes linked to the minimal cytokine inducible VCAM-1 promoter. Nuclear
      IRF-1 is the molecular basis of IFN enhancement, because (a) IFN plus TNF-treated
      cells displayed increased nuclear IRF-1 levels and increased IRF-1 binding to the
      VCAM-1 promoter, compared with cells treated with TNF alone; (b) kinetics of
      nuclear IRF-1 levels correlated with VCAM-1 mRNA levels; (c) transfection with an
      IRF-1 construct substituted for IFN treatment; and (d) transfection with an
      expression construct encoding IRF-2, a competitive inhibitor of IRF-1, reduced
      TNF-induced VCAM-1 expression. Our experiments show that IFN amplifies TNF
      induced VCAM-1 expression at the transcriptional level by an IRF-1-dependent
      pathway.

PMID- 9625762
TI  - Nuclear factor of activated T cells (NFAT)-dependent transactivation regulated by
      the coactivators p300/CREB-binding protein (CBP).
AB  - p300 and cAMP response element-binding protein (CREB)-binding protein (CBP) are
      members of a family of coactivators involved in the regulation of transcription
      and chromatin. We show that transcription factors of the nuclear factor of
      activated T cells (NFAT) family bind p300/CBP and recruit histone
      acetyltransferase activity from T cell nuclear extracts. The NH2-terminal
      transactivation domain of NFAT1 and the phospho-CREB- and E1A-binding sites of
      p300/CBP are involved in the interaction. The viral oncoprotein E1A inhibits NFAT
      dependent transactivation in a p300-dependent manner. Recruitment of the
      coactivators p300/CBP by the transactivation domains of NFAT proteins is likely
      to play a critical role in NFAT-dependent gene expression during the immune
      response.

PMID- 9625763
TI  - Extrathymic T cell deletion and allogeneic stem cell engraftment induced with
      costimulatory blockade is followed by central T cell tolerance.
AB  - A reliable, nontoxic method of inducing transplantation tolerance is needed to
      overcome the problems of chronic organ graft rejection and immunosuppression
      related toxicity. Treatment of mice with single injections of an anti-CD40 ligand
      antibody and CTLA4Ig, a low dose (3 Gy) of whole body irradiation, plus fully
      major histocompatibility complex-mismatched allogeneic bone marrow
      transplantation (BMT) reliably induced high levels (>40%) of stable (>8 mo)
      multilineage donor hematopoiesis. Chimeric mice permanently accepted donor skin
      grafts (>100 d), and rapidly rejected third party grafts. Progressive deletion of
      donor-reactive host T cells occurred among peripheral CD4(+) lymphocytes,
      beginning as early as 1 wk after bone marrow transplantation. Early deletion of
      peripheral donor-reactive host CD4 cells also occurred in thymectomized,
      similarly treated marrow recipients, demonstrating a role for peripheral clonal
      deletion of donor-reactive T cells after allogeneic BMT in the presence of
      costimulatory blockade. Central intrathymic deletion of newly developing T cells
      ensued after donor stem cell engraftment had occurred. Thus, we have shown that
      high levels of chimerism and systemic T cell tolerance can be reliably achieved
      without myeloablation or T cell depletion of the host. Chronic immunosuppression
      and rejection are avoided with this powerful, nontoxic approach to inducing
      tolerance.

PMID- 9625764
TI  - Dermal mast cells determine susceptibility to ultraviolet B-induced systemic
      suppression of contact hypersensitivity responses in mice.
AB  - Different strains of mice have varying susceptibilities to ultraviolet radiation
      (UV) of wavelength 280-320 nm (UVB) for 50% suppression of systemic contact
      hypersensitivity (CHS) responses. Prevalence of histamine-staining dermal mast
      cells in different strains of mice (C57BL/ 6J, DBA/2, BALB/c) correlated directly
      with their susceptibility to UVB-induced systemic immunosuppression. BALB/c mice
      carrying Uvs1, a major locus for susceptibility to UV-induced immunosuppression,
      contained greater numbers of dermal mast cells than BALB/c mice of the same
      parental origin. Strains of mice that were differentiated on their susceptibility
      to UVB-induced downregulation of systemic CHS responses were similar in their
      susceptibility to histamine-induced immunomodulation. Histamine, but not UVB
      irradiation, decreased systemic CHS responses in mast cell-depleted mice (W f/W
      f). Reconstitution of the dorsal skin of W f/W f mice with bone marrow-derived
      mast cell precursors from nonmutant mice rendered the mice susceptible to UVB
      irradiation for systemic suppression of CHS responses. UVB irradiation did not
      suppress delayed type hypersensitivity responses to allogeneic spleen cells in W
      f/W f mice. In contrast, UV irradiation suppressed CHS responses in W f/W f mice
      when hapten was applied to the irradiated site. This study demonstrates that
      dermal mast cells are necessary for the induction of systemic suppression of CHS
      responses by UVB radiation, and suggests that mast cell- derived histamine is one
      component of this UVB-induced systemic immunosuppression.

PMID- 9625765
TI  - Endogenous myelin basic protein inactivates the high avidity T cell repertoire.
AB  - To study the contribution of endogenous myelin basic protein (MBP) to the
      positive and/or negative selection of the MBP-specific T cell repertoire, we
      studied the T cell response to MBP in MBP-deficient shiverer and MBP-expressing
      congenic C3H mice. Immunization with MBP induced a vigorous T cell response in
      shiverer mice directed against a single I-Ak- restricted immunodominant
      determinant, the core of which is peptide MBP:79-87 (DENPVVHFF). Injection of
      this peptide induced a high avidity T cell repertoire in shiverer mice that
      primarily consisted of clones capable of recognizing the native MBP protein in
      addition to the peptide itself. These data show that endogenous MBP is not
      required for the positive selection of an MBP-specific T cell repertoire. C3H
      mice, in contrast, were selectively unresponsive to the MBP protein and injection
      of MBP:79-87 peptide induced a low avidity repertoire that could be stimulated
      only by the peptide, not by the protein. Therefore, endogenous MBP induced
      profound inactivation of high avidity clones specific for the immunodominant
      determinant making that determinant appear cryptic.

PMID- 9625766
TI  - NKp44, a novel triggering surface molecule specifically expressed by activated
      natural killer cells, is involved in non-major histocompatibility complex
      restricted tumor cell lysis.
AB  - After culture in interleukin (IL)-2, natural killer (NK) cells acquire an
      increased capability of mediating non-major histocompatibility complex (MHC)
      restricted tumor cell lysis. This may reflect, at least in part, the de novo
      expression by NK cells of triggering receptors involved in cytolysis. In this
      study we identified a novel 44-kD surface molecule (NKp44) that is absent in
      freshly isolated peripheral blood lymphocytes but is progressively expressed by
      all NK cells in vitro after culture in IL-2. Different from other markers of cell
      activation such as CD69 or VLA.2, NKp44 is absent in activated T lymphocytes or T
      cell clones. Since NKp44 was not detected in any of the other cell lineages
      analyzed, it appears as the first marker specific for activated human NK cells.
      Monoclonal antibody (mAb)-mediated cross-linking of NKp44 in cloned NK cells
      resulted in strong activation of target cell lysis in a redirected killing assay.
      This data indicated that NKp44 can mediate triggering of NK cell cytotoxicity.
      mAb-mediated masking of NKp44 resulted in partial inhibition of cytolytic
      activity against certain (FcgammaR-negative) NK-susceptible target cells. This
      inhibition was greatly increased by the simultaneous masking of p46, another
      recently identified NK-specific triggering surface molecule. These data strongly
      suggest that NKp44 functions as a triggering receptor selectively expressed by
      activated NK cells that, together with p46, may be involved in the process of non
      MHC-restricted lysis. Finally, we show that p46 and NKp44 are coupled to the
      intracytoplasmic transduction machinery via the association with CD3zeta or
      KARAP/DAP12, respectively; these associated molecules are tyrosine phosphorylated
      upon NK cell stimulation.

PMID- 9625767
TI  - Interleukin (IL)-1 receptor-associated kinase (IRAK) requirement for optimal
      induction of multiple IL-1 signaling pathways and IL-6 production.
AB  - Interleukin (IL)-1 is a proinflammatory cytokine with pleiotropic effects in
      inflammation. IL-1 binding to its receptor triggers a cascade of signaling
      events, including activation of the stress-activated mitogen-activated protein
      (MAP) kinases, c-Jun NH2-terminal kinase (JNK) and p38 MAP kinase, as well as
      transcription factor nuclear factor kappaB (NF-kappaB). IL-1 signaling results in
      cellular responses through induction of inflammatory gene products such as IL-6.
      One of the earliest events in IL-1 signaling is the rapid interaction of IL-1
      receptor-associated kinases, IRAK and IRAK-2, with the receptor complex. The
      relative roles of IRAK and IRAK-2 in IL-1 signaling pathways and subsequent
      cellular responses have not been previously determined. To evaluate the
      importance of IRAK in IL-1 signaling, IRAK-deficient mouse fibroblast cells were
      prepared and studied. Here we report that IL-1-mediated activation of JNK, p38,
      and NF-kappaB were all reduced in embryonic fibroblasts deficient in IRAK
      expression. In addition, IL-6 production in response to IL-1 was also
      dramatically reduced in IRAK-deficient embryonic fibroblasts and in skin
      fibroblasts prepared from IRAK-deficient mice. Our results demonstrate that IRAK
      plays an essential proximal role in coordinating multiple IL-1 signaling pathways
      for optimal induction of cellular responses.

PMID- 9625768
TI  - Ku70 is required for late B cell development and immunoglobulin heavy chain class
      switching.
AB  - Immunoglobulin (Ig) heavy chain (HC) class switch recombination (CSR) is a late B
      cell process that involves intrachromosomal DNA rearrangement. Ku70 and Ku80 form
      a DNA end-binding complex required for DNA double strand break repair and V(D)J
      recombination. Ku70(-/-) (K70T) mice, like recombination activating gene (RAG)-1-
      or RAG-2-deficient (R1T or R2T) mice, have impaired B and T cell development at
      an early progenitor stage, which is thought to result at least in part from
      defective V(D)J recombination (Gu, Y., K.J. Seidl, G.A. Rathbun, C. Zhu, J.P.
      Manis, N. van der Stoep, L. Davidson, H.L. Cheng, J.M. Sekiguchi, K. Frank, et
      al. 1997. Immunity. 7:653-665; Ouyang, H., A. Nussenzweig, A. Kurimasa, V.C.
      Soares, X. Li, C. Cordon-Cardo, W. Li, N. Cheong, M. Nussenzweig, G. Iliakis, et
      al. 1997. J. Exp. Med. 186:921-929). Therefore, to examine the potential role of
      Ku70 in CSR, we generated K70T mice that carry a germline Ig HC locus in which
      the JH region was replaced with a functionally rearranged VH(D)JH and Ig lambda
      light chain transgene (referred to as K70T/HL mice). Previously, we have shown
      that B cells from R1T or R2T mice carrying these rearranged Ig genes (R1T/HL or
      R2T/HL mice) can undergo CSR to IgG isotypes (Lansford, R., J. Manis, E. Sonoda,
      K. Rajewsky, and F. Alt. 1998. Int. Immunol. 10:325-332). K70T/HL mice had
      significant numbers of peripheral surface IgM+ B cells, which generated serum IgM
      levels similar to those of R2T/HL mice. However, in contrast to R2T/HL mice,
      K70T/HL mice had no detectable serum IgG isotypes. In vitro culture of K70T/HL B
      cells with agents that induce CSR in normal or R2T/HL B cells did lead to the
      induction of germline CH transcripts, indicating that initial signaling pathways
      for CSR were intact in K70T/HL cells. However, treatment with such agents did not
      lead to detectable CSR by K70T/HL B cells, and instead, led to cell death within
      72 h. We conclude that Ku70 is required for the generation of B cells that have
      undergone Ig HC class switching. Potential roles for Ku70 in the CSR process are
      discussed.

PMID- 9625769
TI  - beta1 integrins are critically involved in neutrophil locomotion in extravascular
      tissue In vivo.
AB  - Recruitment of leukocytes from blood to tissue in inflammation requires the
      function of specific cell surface adhesion molecules. The objective of this study
      was to identify adhesion molecules that are involved in polymorphonuclear
      leukocyte (PMN) locomotion in extravascular tissue in vivo. Extravasation and
      interstitial tissue migration of PMNs was induced in the rat mesentery by
      chemotactic stimulation with platelet-activating factor (PAF; 10(-7) M).
      Intravital time-lapse videomicroscopy was used to analyze migration velocity of
      the activated PMNs, and the modulatory influence on locomotion of locally
      administered antibodies or peptides recognizing various integrin molecules was
      examined. Immunofluorescence flow cytometry revealed increased expression of
      alpha4, beta1, and beta2 integrins on extravasated PMNs compared with blood PMNs.
      Median migration velocity in response to PAF stimulation was 15.5 +/- 4.5
      micron/min (mean +/- SD). Marked reduction (67 +/- 7%) in motility was observed
      after treatment with mAb blocking beta1 integrin function (VLA integrins),
      whereas there was little, although significant, reduction (22 +/- 13%) with beta2
      integrin mAb. Antibodies or integrin-binding peptides recognizing alpha4beta1,
      alpha5beta1, or alphavbeta3 were ineffective in modulating migration velocity.
      Our data demonstrate that cell surface expression of beta1 integrins, although
      limited on blood PMNs, is induced in extravasated PMNs, and that members of the
      beta1 integrin family other than alpha4beta1 and alpha5beta1 are critically
      involved in the chemokinetic movement of PMNs in rat extravascular tissue in
      vivo.

PMID- 9625770
TI  - The human toll signaling pathway: divergence of nuclear factor kappaB and
      JNK/SAPK activation upstream of tumor necrosis factor receptor-associated factor
      6 (TRAF6).
AB  - The human homologue of Drosophila Toll (hToll) is a recently cloned receptor of
      the interleukin 1 receptor (IL-1R) superfamily, and has been implicated in the
      activation of adaptive immunity. Signaling by hToll is shown to occur through
      sequential recruitment of the adapter molecule MyD88 and the IL-1R-associated
      kinase. Tumor necrosis factor receptor-activated factor 6 (TRAF6) and the nuclear
      factor kappaB (NF-kappaB)-inducing kinase (NIK) are both involved in subsequent
      steps of NF-kappaB activation. Conversely, a dominant negative version of TRAF6
      failed to block hToll-induced activation of stress-activated protein kinase/c-Jun
      NH2-terminal kinases, thus suggesting an early divergence of the two pathways.

PMID- 9625771
TI  - Murine macrophages secrete interferon gamma upon combined stimulation with
      interleukin (IL)-12 and IL-18: A novel pathway of autocrine macrophage
      activation.
AB  - Interferon (IFN)-gamma, a key immunoregulatory cytokine, has been thought to be
      produced solely by activated T cells and natural killer cells. In this study, we
      show that murine bone marrow- derived macrophages (BMMPhi) secrete large amounts
      of IFN-gamma upon appropriate stimulation. Although interleukin (IL)-12 and IL-18
      alone induce low levels of IFN-gamma mRNA transcripts, the combined stimulation
      of BMMPhi with both cytokines leads to the efficient production of IFN-gamma
      protein. The macrophage-derived IFN-gamma is biologically active as shown by
      induction of inducible nitric oxide synthase as well as upregulation of CD40 in
      macrophages. Our findings uncover a novel pathway of autocrine macrophage
      activation by demonstrating that the macrophage is not only a key cell type
      responding to IFN-gamma but also a potent IFN-gamma-producing cell.

PMID- 9625772
TI  - Developmentally regulated extinction of Ly-49 receptor expression permits
      maturation and selection of NK1.1+ T cells.
AB  - Clonally distributed inhibitory receptors negatively regulate natural killer (NK)
      cell function via specific interactions with allelic forms of major
      histocompatibility complex (MHC) class I molecules. In the mouse, the Ly-49
      family of inhibitory receptors is found not only on NK cells but also on a minor
      (NK1.1+) T cell subset. Using Ly-49 transgenic mice, we show here that the
      development of NK1.1+ T cells, in contrast to NK or conventional T cells, is
      impaired when their Ly-49 receptors engage self-MHC class I molecules. Impaired
      NK1.1+ T cell development in transgenic mice is associated with a failure to
      select the appropriate CD1-reactive T cell receptor repertoire. In normal mice,
      NK1.1+ T cell maturation is accompanied by extinction of Ly-49 receptor
      expression. Collectively, our data imply that developmentally regulated
      extinction of inhibitory MHC-specific receptors is required for normal NK1.1+ T
      cell maturation and selection.

PMID- 9625773
TI  - Molecular analyses of tight junction physiology: insights and paradoxes.

PMID- 9625774
TI  - Nature of the elements transporting long-chain fatty acids through the red cell
      membrane.
AB  - Docosahexaenoic acid is found to be bound to three equivalent sites on albumin
      with the same affinities as palmitic acid at 0-38 degreesC, which demonstrates
      that ethene-1,2-diyl- and methylene-groups contribute equally to the affinity.
      The equilibrium dissociation constants (Kdms) for red cell membrane binding sites
      of linoleic- and docosahexaenoic acid at pH 7.3 are determined at temperatures
      between 0 and 37 degrees C. The temperature-independent capacities for binding
      are 12 +/- 1 and 25.4 +/- 3.0 nmoles g-1 ghosts respectively. Double isotope
      binding experiments reveal that the unsaturated fatty acids: arachidonic-,
      linoleic-, docosahexaenoic-, and oleic acid have partially shared capacities in
      ratios approximately 1:2:4:5, in contrast to the noncompetitive binding of
      palmitic acid. The observations suggest a two-tier binding limitation. One is the
      number of protein sites binding fatty acid anions electrostatically and the other
      is the number of suitable annular lipids adaptively selected among membrane
      lipids by the hydrocarbon chain. These competition conditions are confirmed by
      measurements of the tracer exchange efflux at near 0 degrees C from albumin-free
      and albumin-filled ghosts of linoleic- and docosahexaenoic acid, either alone or
      in the presence of arachidonic- and palmitic acid. Under equilibrium conditions,
      the calculated ratios of inside to outside membrane binding is below 0.5 for four
      unsaturated fatty acids. The unidirectional rate constants of translocation
      between the inside and the outside correlate with the number of double bonds in
      these fatty acids, which are also correlated with the dissociation rate constants
      of the complexes with albumin. The membrane permeation occurs presumably by
      binding of the anionic unsaturated fatty acids to an integral protein followed by
      channeling of the neutral form between opposite binding sites of the protein
      through annular lipids encircling the protein.

PMID- 9625775
TI  - Transient activity of excitatory Cl- channels in Chara: evidence for quantal
      release of a gating factor.
AB  - In attached patches on the plasma membrane of nonexcited Chara corallina cells,
      randomly activating, transient Cl- currents with variable amplitudes were
      recorded. The peak amplitudes of these currents could be grouped into distinct
      populations with approximately equidistant mean peak currents. Generally, the
      mean current of the smallest population measured about half of the distance
      between the means of subsequent populations. Currents of the smallest population
      occurred most frequently at all voltages; the frequency of observations decreased
      with increasing amplitudes of the currents. At all voltages transient currents
      from different populations were similar in duration with the exception of the
      smallest currents, which lasted only 0.6 times as long as larger currents.
      Furthermore, transient currents were most frequent at positive voltages, but once
      initiated at a positive conditioning pulse they were also observed during
      subsequent pulses to negative voltages. The results are consistent with the idea
      that Chara contains Ca2+ stores in the vicinity of the plasma membrane, which are
      indirectly filled from the external medium. Upon quantal Ca2+ discharge from
      adjacent stores, a process independent of membrane voltage, the concentration of
      Ca2+ in the cytoplasm increases transiently. Depending on the number of
      discharging stores, distinct numbers of Ca2+-stimulated Cl- channels activate,
      giving rise to the macroscopic excitatory Cl- current in these cells.

PMID- 9625776
TI  - Activation of K-Cl cotransport by mild warming in guinea pig red cells.
AB  - Unidirectional, ouabain-insensitive K+ influx rose steeply with warming at
      temperatures above 37 degreesC in guinea pig erythrocytes incubated in isotonic
      medium. The only component of ouabain-insensitive K+ influx to show the same
      steep rise was K-Cl cotransport (Q10 of 10 between 37 and 41 degrees C); Na-K-Cl
      cotransport remained constant or declined and residual K+ influx in hypertonic
      medium with ouabain and bumetanide rose only gradually. Similar results were
      obtained for unidirectional K+ efflux. Thermal activation of K-Cl cotransport
      mediated K+ influx was fully dependent on the presence of chloride in the medium;
      none occurred with nitrate replacing chloride. The increase of K+ influx through
      K-Cl cotransport from 37 to 41 degrees C was blocked by calyculin A, a
      phosphatase inhibitor. The Q10 of K-Cl cotransport fully activated by
      hydroxylamine and hypotonicity was about 2. The time course of K+ entry showed an
      immediate transition to a higher rate when cells were instantly warmed from 37 to
      41 degrees C, but there was a 7-min time lag in returning to a lower rate when
      cells were cooled from 41 to 37 degrees C. These results indicate that the
      steepness of the response of K-Cl cotransport to mild warming is due to altered
      regulation of the transporter. Total unidirectional K+ influx was equal to total
      unidirectional K+ efflux at 37-45 degrees C, but K+ influx exceeded K+ efflux at
      41 degrees C when K-Cl cotransport was inhibited by calyculin or prevented by
      hypertonic incubation. The net loss of K+ that results from the thermal
      activation of isosomotic K-Cl cotransport reported here would offset a tendency
      for cell swelling that could arise with warming through an imbalance of pump and
      leak for Na+ or for K+.

PMID- 9625777
TI  - Adrenergic stimulation of Na/K pump current in adult rat cardiac myocytes in
      short-term culture.
AB  - Passive membrane properties, steady-state Na/K pump current (Ip) and modulation
      of Ip by adrenergic agonists were studied with patch-clamp techniques in adult
      rat ventricular myocytes that were freshly isolated or maintained in culture for
      1-4 days. Freshly isolated (day 0) myocytes had a 1.7-1.8 times smaller specific
      membrane resistance compared with that of cells on any day in culture. From day 0
      to 4 there was a progressive decrease in cell capacitance (-17.6 +/- 0.8 pF/day)
      without a parallel decline in cell dimensions. The pump current density (1.55
      pA/pF) was stable over the 0-4 days in culture. In rod-shaped myocytes
      norepinephrine (NE) and isoproterenol (ISO) stimulated Ip in a dose-dependent
      manner, with an apparent affinity of 36 +/- 8 and 1.5 +/- 0.4 nM, and maximum
      stimulation of 0.65 +/- 0.02 and 0.57 +/- 0.02 pA/pF, respectively. Nadolol
      suppressed this effect, suggesting that it was mediated by beta-adrenergic
      receptor activation. An inverse relationship was found between steady-state Ip
      and the stimulation of Ip by NE. In contrast to what was shown in guinea pig
      cardiac myocytes, in rat myocytes isoproterenol stimulation of Ip was not
      increased by intracellular [Ca] and it did not change the Ip-membrane potential
      relation. These results show that in adult rat cardiac myocytes NE and ISO are
      potent stimulators of Na/K pump activity, and this effect may be studied using
      rat myocytes maintained in short-term culture.

PMID- 9625778
TI  - Chemical modification reveals involvement of different sites for nucleotide
      analogues in the phosphatase activity of the red cell calcium pump.
AB  - The calcium pump of plasma membranes catalyzes the hydrolysis of ATP and
      phosphoric esters like p-nitrophenyl phosphate (pNPP). The latter activity
      requires the presence of ATP and/or calmodulin, and Ca2+ [22, 25]. We have
      studied the effects of nucleotide-analogues and chemical modifications of
      nucleotide binding sites on Ca2+-pNPPase activity. Treatment with fluorescein
      isothiocyanate (FITC), abolished Ca2+-ATPase and ATP-dependent pNPPase, but
      affected only 45% of the calmodulin-dependent pNPPase activity. The nucleotide
      analogue eosin-Y had an inhibitory effect on calmodulin-dependent pNPPase
      (Kieosin-Y = 2 microM). FITC treatment increased Kieosin-Y 15 times. Acetylation
      of lysine residues with N-hydroxysuccinimidyl acetate inactivates Ca2+-ATPase by
      modifying the catalytic site, and impairs stimulation by modulators by modifying
      residues outside this site [9]. Acetylation suppressed the ATP-dependent pNPPase
      with biphasic kinetics. ATP or pNPP during acetylation cancels the fast component
      of inactivation. Acetylation inhibited only partially the calmodulin-dependent
      pNPPase, but neither ATP nor pNPP prevented this inactivation. From these results
      we conclude: (i) ATP-dependent pNPPase depends on binding of ATP to the catalytic
      site; (ii) the catalytic site plays no role in calmodulin-dependent pNPPase. The
      decreased affinity for eosin-Y of the FITC-modified enzyme, suggests that the
      sites for these two molecules are closely related but not overlapped.
      Acetimidation of the pump inhibited totally the calmodulin-dependent pNPPase, but
      only partially the ATP-pNPPase. Since calmodulin binds to E1, the E1 conformation
      or the E2 if E1 transition would be involved during calmodulin-dependent pNPPase
      activity.

PMID- 9625779
TI  - Evidence for negative charge in the conduction pathway of the cardiac ryanodine
      receptor channel provided by the interaction of K+ channel N-type inactivation
      peptides.
AB  - We have investigated the interaction of two peptides (ShB - net charge +3 and
      ShB:E12KD13K - net charge +7) derived from the NH2-terminal domain of the Shaker
      K+ channel with purified, ryanodine-modified, cardiac Ca2+-release channels
      (RyR). Both peptides produced well resolved blocking events from the cytosolic
      face of the channel. At a holding potential of +60 mV the relationship between
      the probability of block and peptide concentration was described by a single-site
      binding scheme with 50% saturation occurring at 5.92 +/- 1.06 microM for ShB and
      0.59 +/- 0. 14 nM for ShB:E12KD13K. The association rates of both peptides varied
      with concentration (4.0 +/- 0.4 sec-1 microM-1 for ShB and 2000 +/- 200 sec-1
      microM-1 for ShB:E12KD13K); dissociation rates were independent of concentration.
      The interaction of both peptides was influenced by applied potential with the
      bulk of the voltage-dependence residing in Koff. The effectiveness of the
      inactivation peptides as blockers of RyR is enhanced by an increase in net
      positive charge. As is the case with inactivation and block of K+ channels, this
      is mediated by a large increase in Kon. These observations are consistent with
      the proposal that the conduction pathway of RyR contains negatively charged sites
      which will contribute to the ion handling properties of this channel.

PMID- 9625780
TI  - The effect of electrical deformation forces on the electropermeabilization of
      erythrocyte membranes in low- and high-conductivity media.
AB  - Electrical breakdown of erythrocytes induces hemoglobin release which increases
      markedly with decreasing conductivity of the pulse medium. This effect presumably
      results from the transient, conductivity-dependent deformation forces (elongation
      or compression) on the cell caused by Maxwell stress. The deformation force is
      exerted on the plasma membrane of the cell, which can be viewed as a transient
      dipole induced by an applied DC electric field pulse. The induced dipole arises
      from the free charges that accumulate at the cell interfaces via the Maxwell
      Wagner polarization mechanism. The polarization response of erythrocytes to a DC
      field pulse was estimated from the experimental data obtained by using two
      complementary frequency-domain techniques. The response is very rapid, due to the
      highly conductive cytosol. Measurements of the electrorotation and
      electrodeformation spectra over a wide conductivity range yielded the information
      and data required for the calculation of the deformation force as a function of
      frequency and external conductivity and for the calculation of the transient
      development of the deformation forces during the application of a DC-field pulse.
      These calculations showed that (i) electric force precedes and accompanies
      membrane charging (up to the breakdown voltage) and (ii) that under low
      conductivity conditions, the electric stretching force contributes significantly
      to the enlargement of "electroleaks" in the plasma membrane generated by electric
      breakdown.

PMID- 9625781
TI  - High-frequency DNA rearrangements in the chromosomes of clinically isolated
      Mycoplasma fermentans.
AB  - Mycoplasma fermentans is currently being examined as an agent potentially
      associated with human disease. Several strains of M. fermentans were isolated
      from patients with respiratory tract disease and AIDS. Two of these clinical
      strains, M64 and SK6, were triple-filter-cloned and designated as the parental
      clones in this study. Genomic DNA of randomly picked subclones in four and five
      subsequent generations passed from the parental M64 and SK6 clones were analyzed
      by using a radiolabeled M. fermentans-specific insertion sequence (IS)-like
      element as the probe. The hybridization patterns of DNA restriction fragments
      revealed high frequencies of chromosomal changes accompanied with excision or new
      insertion of the IS-like element in M. fermentans chromosome. The findings
      indicate M. fermentans has an effective mechanism(s) to produce a rapid gene
      rearrangement that may be mediated by one or more copies of the IS-like element.

PMID- 9625782
TI  - Target range of zwittermicin A, an aminopolyol antibiotic from Bacillus cereus.
AB  - Zwittermicin A is a novel antibiotic produced by Bacillus cereus UW85, which
      suppresses certain plant diseases in the laboratory and in the field. We
      developed a rapid method for large-scale purification of zwittermicin A and then
      studied the in vitro activity of zwittermicin A against bacteria, fungi, and
      protists. Zwittermicin A was highly active against the Oomycetes and their
      relatives, the algal protists, and had moderate activity against diverse Gram
      negative bacteria and certain Gram-positive bacteria as well as against a wide
      range of plant pathogenic fungi. Zwittermicin A was more active against bacteria
      and fungi at pH 7-8 than at pH 5-6. When zwittermicin A was combined with
      kanosamine, another antibiotic produced by B. cereus, the two acted
      synergistically against Escherichia coli and additively against Phytophthora
      medicaginis, an Oomycete. The results indicate that there are diverse potential
      applications of this new class of antibiotic.

PMID- 9625783
TI  - Calcium transport by Frankia sp. strain EAN1pec.
AB  - When incubated at 25 degrees C, N2-grown cells of Frankia strain EAN1pec actively
      accumulated calcium, while NH4Cl-grown cells did not accumulate calcium. When
      incubated at 0 degrees C, both N2-grown and NH4Cl-grown cells did not actively
      accumulate calcium. Inhibitors of respiration inhibited calcium accumulation by
      N2-grown cells at 25 degrees C. Isolated vesicles also accumulated calcium in an
      energy- and temperature-dependent manner. Two lines of evidence show that Frankia
      strain EAN1pec has an active calcium extrusion mechanism. First, NH4Cl-grown
      cells incubated under deenergizing conditions accumulated calcium. Second,
      calcium efflux from calcium-loaded cells required an energy source and was
      blocked by inhibitors. The results of this study indicate that Frankia strain
      EAN1pec has two systems for calcium transport: a calcium extrusion system and a
      developmentally regulated calcium uptake system.

PMID- 9625784
TI  - Cloning, sequence, and expression of the phosphofructokinase gene of Clostridium
      acetobutylicum ATCC 824 in Escherichia coli.
AB  - The pfk gene encoding phosphofructokinase (Pfk) from the anaerobic bacterium
      Clostridium acetobutylicum ATCC 824 was cloned and sequenced. The gene was
      identified in a plasmid library by complementation of an E. coli pfk mutant and
      by the ability to amplify a fragment by PCR using primers based on homologous
      regions of Pfk from other microorganisms. Nucleotide sequence analysis revealed a
      coding region for a 319-aa protein homologous to Pfks from other organisms.
      Enzyme assay and ability to complement the growth defects of E. coli pfk mutants
      confirmed the expression of the clostridial pfk gene. The pyruvate kinase (pyk)
      gene was identified adjacent to pfk. Such an arrangement for the genes encoding
      key regulators of glycolytic flux had not yet been described in a strict
      anaerobe. This gene arrangement has been found in other Gram-positive organisms,
      but not in Gram-negative organisms.

PMID- 9625785
TI  - Removal of waterborne human enteric viruses and coliphages with oxidized coal.
AB  - Human enteric viruses and coliphages have been detected in water that has
      undergone what is generally considered adequate treatment, including
      chlorination. Because small numbers of virus particles are needed for the
      initiation of a productive virus infection, the presence of any number of virus
      particles in water resources will always be of concern. In this investigation the
      ability of oxidized coal to remove viruses from water was investigated. The
      oxicoal product was found to be able to remove not only coliphages, but also
      various pathogenic human viruses from seeded water sources. Removal was dependent
      upon the type of virus, the period of exposure, and the concentration of oxidized
      coal.

PMID- 9625786
TI  - Incidence of non-01 Vibrio cholerae and Aeromonas spp. in fresh water in
      Araraquara, Brazil.
AB  - The occurrence of Aeromonas spp., Vibrio cholerae, and Plesiomonas shigelloides
      in fresh water from various sources in Araraquara, State of Sao Paulo, Brazil was
      determined. Samples from ten distinct irrigation systems used in vegetable
      cultivation, from five distinct streams, from two reservoirs, from one artificial
      lake, and from three distinct springs were analyzed. All isolates were serotyped
      and tested for hemolysin, cytotoxin, heat-stable (ST) and heat-labile (LT)
      enterotoxins production; presence of plasmid; autoagglutination and drug
      resistance. V. cholerae isolates were also tested for cholera enterotoxin (CT)
      production, and Aeromonas isolates for suicide phenomenon. No P. shigelloides was
      found. V. cholerae non 01 was found in five irrigation water samples and in three
      stream samples. Aeromonas sp. were isolated in two samples of irrigation water,
      in three streams, and in one reservoir. All the V. cholerae and Aeromonas
      isolates were positive for beta-hemolysin production, and all Aeromonas isolates
      were positive for suicide phenomenon; cytotoxic activities were observed in two
      Aeromonas strains. Cholera enterotoxin was not found in eight V. cholerae non-01
      isolates tested by the Y-1 mouse adrenal cell. All isolates were also negative
      for the other virulence markers. V. cholerae isolates were found to be sensitive
      to the majority of drugs tested, while Aeromonas strains presented multiple drug
      resistance.

PMID- 9625787
TI  - The phosphorylation of light-harvesting polypeptides LHIalpha (B870) and
      LHIIalpha (B800-850) of Rhodobacter capsulatus B10 was higher under chemotrophic
      oxic than under phototrophic anoxic growth conditions.
AB  - In Rhodobacter capsulatus B10 (wild type) both alpha subunits of the light
      harvesting complexes are phosphorylated during photosynthetic membrane synthesis.
      During the process of insertion of these polypeptides, there is a
      dephosphorylation resulting in intracytoplasmic membranes in which no radioactive
      phosphate could be detected. Moreover, we show that their phosphate-specific
      contents depends on the growth conditions, the highest being observed under oxic
      conditions. When photosynthetic membrane synthesis was induced under light and
      anaerobiosis, a decrease in the phosphate-specific contents ensued. An inverse
      relationship exists between specific phosphorylation levels and the degree of
      membrane differentiation. The phosphorylation is thus a transient phenomenon
      characteristic of the photosynthetic membrane synthesis governed by the external
      redox conditions constituting an additional post-transcriptional level of
      regulation.

PMID- 9625788
TI  - Isolation of a beta-galactosidase-encoding gene from Bacillus licheniformis:
      purification and characterization of the recombinant enzyme expressed in
      Escherichia coli.
AB  - The Bacillus licheniformis beta-galactosidase gene, lacBl, was cloned on a 5.8-kb
      HindIII fragment into pBR322 and expressed by its own promoter in Escherichia
      coli. Deletion and complementation analysis showed that the enzyme-encoding
      region was located on a 4. 1-kb HindIII-ClaI fragment. The transcription region
      for the lacBl was identified on this fragment with promoter- and terminator-probe
      plasmids. The deduced sequence of 149 aa of the N-terminal part of lacBl showed
      aa sequence homology with beta-Gal from B. stearothermophilus, B. circulans,
      Haloferax alicantei, Clostridium perfringens, Arthrobacter sp.. No significant
      homology was shared with those found in the lacZ and lacS families. The
      recombinant beta-galactosidase (LacB1) was purified by FPLC. The molecular mass
      of the enzyme (80 kDa) and its optimal pH (5.7) and temperature (45 degrees C)
      were determined.

PMID- 9625789
TI  - Isolation and characterization of Helicobacter species from the stomach of the
      house musk shrew (Suncus murinus) with chronic gastritis.
AB  - A Gram-negative, motile bacterium with bipolar sheathed flagella (one at each
      end) was isolated from the stomach of house musk shrews (Suncus murinus) with
      chronic gastritis. The isolates grew at 37 degrees C under microaerophilic
      conditions, but not under aerobic conditions; rapidly hydrolyzed urea; were
      catalase, oxidase, alkaline phosphatase, and arginine aminopeptidase positive;
      reduced nitrate to nitrite; and were resistant to cephalothin and nalidixic acid,
      but sensitive to tetracycline, erythromycin, and chloramphenicol. This bacterium
      was found on gastric epithelial cells by electron microscopy. In addition, a
      coccoid form of the bacteria was found in vacuoles formed in the epithelial cells
      of some of the house musk shrews tested. These results, including 16S rRNA gene
      sequence analysis, strongly suggested that this bacterium should be classified as
      a novel Helicobacter species. It is proposed that this bacterium should be called
      "Helicobacter suncus."

PMID- 9625790
TI  - Biological, immunological, and genetic analysis of Bacillus thuringiensis
      isolated from granary in Korea.
AB  - To isolate a naturally occurring novel Bacillus thuringiensis strain, we
      investigated the distribution, toxicity, morphology, H serotype, and gene type of
      B. thuringiensis from residue samples of granary in Korea. A total of 163 B.
      thuringiensis isolates out of 411 samples producing spore and crystal were
      obtained. In toxicity tests, 80% of all isolates were toxic to lepidoptera, and
      12% were not toxic to any of tested insects. And dipteran-active and
      lepidopteran/dipteran-active isolates were rare (2% and 6%, respectively). 152 B.
      thuringiensis isolates produced typical rhomboidal crystals, and the remainder
      produced parasporal inclusions with various morphologies. Serological test showed
      that B. thuringiensis isolates in granary represented 12 H serotypes, indicating
      varied distribution of B. thuringiensis. Of these, the serotype 3ab predominated,
      followed by the serotype 7 and 4ac. B. thuringiensis isolates of the serotype
      3ab, 4ac, 5ab, 7, 8ab, 9, and 23 were toxic to lepidoptera, and the serotype 8bd,
      12, 18, and 20ac were nontoxic, while 14 isolates were untypable by 33 B.
      thuringiensis H antisera. The frequency of toxicity against lepidoptera and
      diptera was primarily highly toxic. PCR analysis using cryI gene type-specific
      primers showed that cryIA(b) genes are frequently found and cryIE gene exists in
      only one isolate. Analysis of B. thuringiensis crystals and plasmid DNAs
      indicated a diversity of crystal and gene types.

PMID- 9625791
TI  - The endosymbiont (Buchnera) of the aphid Diuraphis noxia contains all the genes
      of the tryptophan biosynthetic pathway.
AB  - Previously it has been shown that the prokaryotic endosymbiont (Buchnera) of the
      aphid Diuraphis noxia contains a plasmid consisting of one copy of the gene for
      anthranilate synthase (trpEG) and seven trpEG pseudogenes. In the present
      communication we show that this endosymbiont contains the remaining genes of the
      tryptophan biosynthetic pathway [trpDC(F)BA] which appear to be functional in
      that they code for the complete enzyme proteins and are not pseudogenes. As in
      the case of Buchnera from other endosymbionts, these genes appear to be organized
      as one transcription unit and are located on the endosymbiont chromosome.

PMID- 9625792
TI  - Purification and characteristics of membrane-bound chitinase of anaerobic ruminal
      fungus Piromyces communis OTS1.
AB  - A membrane-bound chitinase from cell wall fractions of the anaerobic ruminal
      fungus, Piromyces communis OTS1, was purified by affinity chromatography, gel
      filtration, and chromatofocusing. The molecular size of the chitinase was
      estimated by gel filtration to be 42.4 kDa and by SDS-PAGE to be 44.8 kDa, and
      its pI was 4.4. Activity was inhibited by Hg2+ and allosamidin. The activity at
      39 degrees C was greatest at pH 6.0. It had an 'endo' type action. Solubilization
      tests indicated that plasmalemma-bound chitinase was held in place by an
      electrostatic type interaction. Characterization of the membrane-bound chitinase
      was more similar to that of extracellular chitinase than cytosolic chitinase.
      This suggested that membrane-bound chitinase was the origin of extracellular
      chitinase.

PMID- 9625793
TI  - On the iron requirement of lactobacilli grown in chemically defined medium.
AB  - The iron requirement of four strains of lactobacilli (L. acidophilus, L.
      delbrueckii subsp. bulgaricus, L. plantarum, and L. pentosus) was studied in a
      synthetic medium under aerobic or anaerobic conditions. Effects of iron salt and
      iron-chelated compounds were tested on bacterial growth in manganese-free or 
      supplemented media. No significant growth stimulation was observed in any
      condition. These results support the absolute manganese requirement for optimum
      growth of lactobacilli and the needless incorporation of iron in growth media.

PMID- 9625794
TI  - Fungitoxicity of chemical analogs with heartwood toxins.
AB  - Trans-stilbene and tropolone as chemical analogs with naturally occurring
      fungitoxic heartwood compounds were studied with respect to their fungitoxic
      potency. While stilbene showed no fungitoxic activity towards the fungi
      Aureobasidium pullulans var. melanogenum, Penicillium glabrum, and Trichoderma
      harzianum in the concentrations tested, the minimal inhibiting concentration of
      tropolone was 10(-3) M for Penicillium glabrum and Trichoderma harzianum, and 10(
      5) M for Aureobasidium pullulans var. melanogenum. In all cases, the effect of
      tropolone was a fungistatic one. Using chemical analogs for assessing the
      chemical basis of the fungitoxicity of tropolone, this substance proved to be the
      only compound tested which possesses fungitoxic properties.

PMID- 9625795
TI  - Purification and characterization of an arylamine N-acetyltransferase from the
      bacteria Aeromonas hydrophilia.
AB  - N-acetyltransferase from Aeromonas hydrophilia was purified by ultrafiltration,
      DEAE-Sephacel, gel filtration chromatography on Sephadex G-100, and DEAE-5pw on
      high performance liquid chromatography, as judged by sodium dodecyl sulfate
      polyacrylamine gel electrophoresis (SDS-PAGE) on a 12.% (wt/vol) slab gel. The
      enzyme had a molecular mass 44.9 kDa. The purified enzyme was thermostable at 37
      degrees C for 1 h with a half-life 28 min at 37 degrees C, and displayed optimum
      activity at 37 degrees C and pH 7.0. The Km and Vmax values for 2-aminofluorene
      were determined to be 0. 896 mM and 2.456 nmol/min/mg protein, respectively.
      Among a series of divalent cations and salts, Zn2+, Ca2+, and Fe2+ were
      demonstrated to be the most potent inhibitors.

PMID- 9625796
TI  - p73beta, unlike p53, suppresses growth and induces apoptosis of human
      papillomavirus E6-expressing cancer cells.
AB  - Human papillomavirus (HPV) is the major cause of cervical cancer worldwide. HPV
      E6 protein targets the p53 tumor suppressor protein for degradation by ubiquitin
      mediated proteolysis making such cancers resistant to p53-gene therapy. Here we
      show that infection of human cancer cells by E6-expressing adenovirus (Ad-E6)
      leads to degradation of both wild-type or mutant p53 protein. Interestingly, the
      p53-homologue candidate tumor suppressor p73 is not degraded in Ad-E6 infected
      cancer cells. Wild-type p73beta and not wild-type p53 or mutant p73 is a potent
      inhibitor of cancer colony growth and inducer of apoptosis, despite HPV-E6
      overexpression. The results suggest a novel strategy using p73beta in gene
      therapy of HPV-E6 expressing cancers.

PMID- 9625798
TI  - Angiogenesis in hepatocellular carcinoma: an experimental study in the chick
      embryo chorioallantoic membrane.
AB  - Ten samples of human hepatocellular carcinoma and three of a laceration injure of
      the liver (controls) were grafted onto the chick embryo chorioallantoic membrane
      (CAM) to investigate their possible angiogenic activity. The angiogenic response
      in pathological and control implants was assessed on histologic sections by a
      morphometric method, 4 days after grafting. The vascular count in the CAMs
      treated with the pathological implants was significantly higher compared to
      control ones and the angiogenic response induced by pathological implants was
      comparable to that of a well known angiogenic molecule, namely basic fibroblast
      growth factor. The role played in vasoproliferative response by angio-genic
      cytokines released by tumor cells, by CAM extracellular matrix and by the
      perivascular mononuclear cells was supported by this study.

PMID- 9625797
TI  - Potentiation of tumor necrosis factor induced apoptosis by onconase.
AB  - Onconase (ONC) a ribonuclease from amphibian oocytes is cytostatic and cytotoxic
      to many human tumor lines, shows in vivo antitumor activity in mouse tumor models
      and is in Phase III clinical trials. The mechanism of antitumor activity of ONC
      is presumed to be due to its internalization, degradation of intracellular RNA
      and suppression of protein synthesis. Since apoptosis triggered by TNF-alpha is
      known to be potentiated by inhibitors of protein synthesis, we have hypothesized
      that it also may be potentiated by ONC. Indeed, preincubation of U-937 or HL-60
      leukemic cells with 0.17 microM ONC rendered them more sensitive to induction of
      apoptosis by TNF-alpha or antibody to CD95 (Fas). The mechanism by which ONC
      amplifies the effect of TNF-alpha may involve suppression of induction of the
      survival genes whose expression is triggered by activation of NFkB by this
      factor.

PMID- 9625799
TI  - Microsatellite instability in an animal model of mammary carcinogenesis.
AB  - Alterations in the length of simple repetitive genomic sequences (microsatellite
      instability, MSI) may characterize a distinct mechanism of mammary
      carcinogenesis. In order to investigate whether MSI is associated with chemically
      induced mammary carcinogenesis in the rat, 30 microdissected mammary carcinomas
      were analyzed using 27 different microsatellite markers from chromosomes 1, 3, 5,
      7 and 8. DNA was extracted from rat mammary cancer and adjoining microscopically
      normal tissues from the same slide, amplified by PCR, using different polymorphic
      DNA markers and the reaction products were analyzed for microsatellite
      instability. The results of this study indicate that 30% of cases (9 out of 30)
      showed microsatellite instability at a minimum of 1 locus. Three cases (out of
      30) showed microsatellite instability at only three loci or less, called MSI-L
      (low frequency MSI). Six cases (out of 30) showed MSI at four loci or more,
      called MSI-H (high frequency MSI). Six cases showed MSI at D5Mit11 and D5Mgh3
      loci, five cases showed MSI at D1Mit14, D1Mgh6, D5Mgh5 and D8Mgh10 loci, four
      cases had MSI at D1Mgh2, and D3Mgh7 loci, three cases had MSI at D3Mit3, D3Mgh5,
      D7Mgh1 loci, two cases had MSI at D7Mit11 locus and one case had MSI at D3Mgh9
      locus. The results of these experiments suggest that MSI may be an important
      etiological event in the pathophysiology of mammary carcinogenesis.

PMID- 9625800
TI  - Evaluation of benzyl selenocyanate glutathione conjugate for potential
      chemopreventive properties in colon carcinogenesis.
AB  - Observational, clinical and experimental studies have suggested that dietary
      supplementation with selenium can inhibit the development of colon cancer. Since
      toxicity and chemopreventive efficacy of selenium compounds depend to a large
      extent, on the form of selenium the development of efficacious organoselenium
      compounds with low toxicity is being pursued in our laboratory. We have assessed
      the chemopreventive properties of a newly synthesized organoselenium compound,
      benzyl selenocyanate glutathione conjugate (BSeSG), and of benzyl selenocyanate
      (BSC), as a positive control, using azoxymethane (AOM)-induced colonic aberrant
      crypt foci (ACF) as a measure of efficacy. Five-week-old male F344 rats were fed
      the control diet (modified AIN-76A) or experimental diets containing 10 or 20 ppm
      BSeSG (1.7 and 3.4 ppm as Se, respectively), or 10 ppm BSC (4.1 ppm as Se). One
      week later, all animals except those in vehicle (normal saline)-treated groups
      were s.c. injected with AOM (15 mg/kg of body weight, once weekly for 2 weeks).
      All animals were sacrificed 7 weeks after the last AOM injection, and the ACF,
      levels of prostaglandin E2 (PGE2), cyclooxygenase protein expression (COX-1 and 
      2), and glutathione S-transferase type mu (GST-mu) were determined in the colon.
      As expected, dietary administration of BSC suppressed ACF development by about
      37%. In rats administered 10 or 20 ppm BSeSG, the frequencies of AOM-induced
      colonic ACF were significantly decreased compared to those of rats given AOM and
      control diet by about 41% (P<0.01) and 61% (P<0.001), respectively.
      Administration of BSeSG inhibited PGE2 production (81-88% inhibition) via COX-2
      synthesis in the colonic mucosa (18-60% inhibition). Also, BSeSG increased GST-mu
      protein activity in colonic mucosa (30-32% increase). These data suggest that a
      newly synthesized organoselenium compound, BSeSG might be a promising
      chemopreventive agent against colon carcinogenesis.

PMID- 9625801
TI  - Genetic and epigenetic influences in prostatic carcinogenesis (review).
AB  - Prostatic carcinogenesis is a multistep process with well-documented stages.
      Although prostate cancer is a major cause of mortality many small tumor foci
      never progress to form clinically significant disease, indicating that the
      disease process may be regulated at more than one level. Carcinogenesis is
      accompanied by increasing genetic damage to prostatic epithelial cells, however
      the pattern of genetic lesions is inconsistent. The differentiation of stromal
      cells surrounding tumors is more fibroblastic and less muscular than in normal
      prostate. The present communication reviews the roles of both genetic and,
      stromally derived, epigenetic effects on prostatic tumorigenesis.

PMID- 9625802
TI  - Unusual potentiation by vinca alkaloids of the cytostatic and cytocidal action of
      methyl-3,5-diiodo-4-(4'-methoxyphenoxy) benzoate (DIME) and its nonhydrolyzable
      ethanone analog (DIPE) on MDA-MB-231 human mammary cancer cells.
AB  - Drug interaction between DIME or DIPE ?1-[3, 5-diiodo-4-(4'-methoxyphenoxy)
      phenyl]-ethanone? with vincristine and vinblastine on the growth rate of MDA-MB
      231 human mammary cancer cells was determined by the median effect kinetic
      method. Mutually exclusive cellular binding sites were identified kinetically and
      isobologram analyses showed potentiation. The combind effect of 0.75 MICROM DIME
      and 2 nM vincristine demonstrated a nearly type of mutual activation. It was
      shown that the nonhydrolyzable DIME derivative DIPE is equivalent to DIME, but
      because of its biological stability is a preferred drug candidate. Vinblastine
      DIME cooperative action is similar to that of vincristine-DIME (or DIPE).
      Activation of caspase 3 by both DIME and vincristine is greatly potentiated when
      both drugs are added simultaneously in a given proportion. We propose that
      following a primary binding of DIME and vinca alkaloids to microtubules, an as
      yet unrecognized mutual activation of caspase 3 apoptotic path is initiated,
      explaining DNA fragmentation and cell death. A subpopulation of cancer cells,
      capable of slow growth at 1.5 microM DIME was identified. This cell type was also
      killed by the DIME-vincristine drug combination.

PMID- 9625803
TI  - Disease-adapted relapse therapy for ovarian cancer: results of a prospective
      study.
AB  - Primary therapy of advanced ovarian cancer is standardized, the therapy in
      relapsed ovarian cancer however is still controversial. In a prospective study
      the benefit of secondary surgery and/or second-line chemotherapy were evaluated.
      139 patients with relapsed ovarian cancer were stratified according to a
      treatment plan: patients with early relapse (recurrence-free interval 12 months)
      or primary progression during chemotherapy (n=43) were treated
      chemotherapeutically with etoposide (p.o. vs. i.v.). Patients with late relapse
      (recurrence-free interval >12 months, n=96) were referred, if possible, to a
      secondary debulking operation, followed by a platinum-based chemotherapy.
      Remission-rate, toxicity and survival time were analyzed. Median survival time in
      the <early relapse> group was 15 months compared to 30 months in patients with
      late relapse (p=0.0004). Within the <late relapse> group patients with secondary
      debulking and chemotherapy (n=59) had a statistically significant survival
      advantage compared to patients who had only chemotherapy (n=37) (38 vs. 12
      months, p<0.0001). The unfavorable group of patients with early relapse should be
      treated chemotherapeutically, whereas in patients with late relapse a secondary
      debulking seems to improve prognosis.

PMID- 9625804
TI  - Correlation between cell cycle regulators and the immortalization and
      transformation of human breast epithelial cell lines.
AB  - Cellular proliferation, essential for normal development, may result in
      neoplastic growth when the cell cycle clock is disrupted. In order to determine
      whether the protein expression of cell cycle regulators differs among normal,
      immortalized non-tumorigenic and malignant human breast epithelial cells (HBECs),
      we analyzed the protein expression of cyclins D1, D3, A and E, cyclin-dependent
      kinase (cdk) 4 and c-fos in exponentially growing MCF-10M, MCF-10F, and MCF-7
      cells. The tumorigenicity of HBECs in vivo correlated with both cell cycle
      regulators and early-gene protein expression in vitro. The differential
      expression of cyclin E- and cyclin A-related proteins and their putative
      relevance in the tumorigenic properties of HBECs are also discussed.

PMID- 9625805
TI  - Antitumor vaccine effect of irradiated murine neuroblastoma cells producing
      interleukin-2 or granulocyte macrophage-colony stimulating factor.
AB  - We have examined vaccination effects of cytokine-producing murine neuroblastoma
      cells (C1300). C1300 cells retrovirally transduced with interleukin-2 (IL-2) or
      granulocyte macrophage-colony stimulation factor (GM-CSF) gene were established.
      Their in vitro proliferation rates and the class I expression of major
      histocompatibility complex were not different from those of wild-type cells. Five
      Gy irradiation of the respective cytokine producers slightly reduced the in vitro
      cell growth but treatment with 15 Gy significantly impaired the proliferation. In
      contrast, the secretion of both cytokines from the respective transduced cells
      was retained compared with the cell growth. We immunized syngeneic mice with
      irradiated wild-type cells as a control or cytokine-producing cells and
      challenged the mice with unirradiated wild-type cells. The control mice developed
      tumors of the challenged wild-type cells, on the contrary, the mice which had
      received irradiated IL-2 or GM-CSF producers did not. Thus, IL-2- or GM-CSF
      expressing syngeneic tumor cells can be potentially used as a tumor vaccine by
      inducing protective immunity against low immunogenic neuroblastomas in the
      inoculated hosts.

PMID- 9625807
TI  - Identification of genes differentially expressed in nasopharyngeal carcinoma by
      messenger RNA differential display.
AB  - We have applied the mRNA differential display method to compare and analyze mRNAs
      prepared from five normal nasopharyngeal epithelial cell cultures and five
      nasopharyngeal carcinoma cell lines. A total of 24 differential display
      experiments was performed using different combinations of PCR primers. Sixty-nine
      cDNA fragments differentially expressed in either normal or malignant
      nasopharyngeal epithelial cells were identified. Subsequent cloning and
      sequencing of these differentially expressed cDNA fragments resulted in the
      identification of seventeen distinct sequences. Seven of these sequences were
      shown to be novel cDNA sequences not previously reported. Ten of the remaining
      cDNA fragments showed sequence homology to previously reported genes.
      Differential expression of four of these seventeen cDNA fragments in normal
      nasopharyngeal epithelial cells was confirmed by reverse Northern hybridization.
      One of these cloned cDNA fragments is a novel cDNA sequence while the other three
      matched to previously reported cDNA sequences involved in cell growth and
      migration. Homologous sequences identified to be differentially expressed in
      normal nasopharyngeal epithelial cells in this study are: human 26 kDa cell
      surface protein (TAPA-1) mRNA, NF-E2 like basic leucine zipper transcriptional
      activator and the human bullous pemphigoid antigen. The mRNA differential display
      is a useful tool to identify candidate genes involved in the pathogenesis of
      nasopharyngeal carcinoma.

PMID- 9625806
TI  - Differential expression and activity of phosphatases and protein kinases in
      adriamycin sensitive and resistant human breast cancer MCF-7 cells.
AB  - Multidrug resistance is one of the major obstacles in cancer chemotherapy. In
      tumor cells, overexpression of the transmembrane P-glycoprotein 170 (P-gp) is
      associated with the multidrug resistance phenotype and serves as a drug efflux
      pump. The activation of P-gp has been suggested to occur at the post
      translational level. Protein kinase C mediated phosphorylation may be associated
      with the drug effux mechanism but the overall phosphorylation pathway has not
      been completely defined. we report the novel finding of an increase in
      phosphatase 1B (a tyrosine phosphatase) and a decrease in PP1 and PP2A
      (serine/threonine phosphatases) expression and activity in our series of early
      (R65) and late (R500) stage adriamycin resistant MCF-7 cells. In addition, we
      show a decrease in protein kinase A (PKA) activity and an increase in protein
      kinase C (PKC) in our drug resistant cells. Analyses of PKC isoforms alpha
      through epsilon revealed that PKCbeta was not expressed and that all other
      isoforms increased with increasing resistance, except PKCgamma which was detected
      only in R65 cells. Our findings suggest that in drug resistant cells, there is a
      pattern consistant with the maintenance of serine and threonine residues in a
      phosphorylated state.

PMID- 9625808
TI  - Therapy-related leukemia and myelodysplasia following oral administration of
      etoposide for recurrent breast cancer.
AB  - We report a high risk of therapy-related acute myeloid leukemia and
      myelodysplastic syndrome (t-AML/MDS) in patients receiving oral administration of
      etoposide for recurrent breast cancer. We examined 119 patients with recurrent
      disease. Patients were initially treated with anthracyclines, cyclophosphamide,
      or cisplatin with or without radiation before etoposide treatment. Etoposide was
      used as the final drug in most cases. Twenty-four patients were treated with the
      oral administration of etoposide (50 or 100 mg/day for 5-7 days at 4-week
      intervals). Three cases of t-AML/MDS developed among those 24 patients exposed to
      etoposide. In contrast, the development of t-AML/MDS was not observed in the
      other 95 patients not treated with etoposide. Our data suggest that there is a
      substantial risk of secondary leukemia with oral administration of etoposide for
      a prolonged period as well as i.v. schedules.

PMID- 9625809
TI  - Fas and Fas ligand system may mediate antiproliferative activity of gonadotropin
      releasing hormone receptor in endometrial cancer cells.
AB  - Gonadotropin-releasing hormone (GnRH) receptor-bearing tumors undergo apoptosis
      in vivo and in vitro with GnRH analogs. We recently showed that GnRH stimulation
      induces intratumoral expression of the apoptosis-inducing Fas ligand in human
      reproductive tract tumors. To provide a potential association of Fas/Fas ligand
      system with the antiproliferative signaling process of GnRH receptor, we
      evaluated a correlation between the Fas ligand expression and the number of
      viable cells in two types of GnRH receptor-bearing endometrial carcinomas that
      differ in Fas content. Surgically removed uterine endometrial carcinomas had been
      screened for the presence of GnRH receptor and Fas before analyses. Fas ligand
      protein was characterized by immunoblotting of membrane proteins with the
      specific antibody. After a lag time of 2 days, incubation with a GnRH analog
      leuprolide (10 microM) induced significant growth inhibition of the Fas- and GnRH
      receptor-bearing cells (p<0.01). Time course analysis showed that Fas ligand
      production, which was already observed at day 2 (p<0.01), precedes the onset of
      reduction in viable cell number. The stimulatory effect of GnRH on Fas ligand
      expression and reduction of viable cells revealed dose-dependency. The analog at
      concentration of 10 microM induced up to 90% reduction in cell number. In
      contrast, the growth of Fas-negative cells was not affected by the analog,
      although Fas ligand appeared in response to the GnRH analog (p<0.01). These data
      demonstrate that the co-presence of Fas could be essential for GnRH to promote
      antiproliferative action in endometrial cancer cells carrying GnRH receptor. The
      hormone may act through intratumor Fas and Fas ligand system to induced growth
      inhibition in GnRH-sensitive tumors.

PMID- 9625810
TI  - Mutation analysis of the putative tumor suppressor PTEN/MMAC1 in human ovarian
      cancer.
AB  - A putative tumor suppressor, PTEN/MMAC1 gene was recently identified at 10q23 and
      was found to be frequently altered in several types of human tumors. To determine
      the possible role of this gene in human ovarian tumors, we screened 31 unselected
      primary epithelial ovarian cancers with matched normal tissues and 7 ovarian
      cancer cell lines. Two homozygous deletions (4.8%) were detected in primary
      ovarian tumors by a semi-quantitative multiplex polymerase chain reaction.
      However, no point mutations were observed in any of the PTEN/MMAC1 coding
      sequences as determined by denaturing high-performance liquid chromatography and
      DNA sequencing. These data indicate that PTEN/MMAC1 mutations are rare in ovarian
      cancers.

PMID- 9625811
TI  - Role of a mutant p53 protein in apoptosis: characterization of a function
      independent of transcriptional trans-activation.
AB  - Wild-type (wt) tumor suppressor p53 has been implicated in cellular
      radiosensitivity, mediated by its role in apoptosis and growth arrest.
      Intriguingly, it was observed that the temperature sensitive (ts) mutant
      p53val135 protein functions as a positive modulator of cellular radiosensitivity,
      as evident from acceleration of irradiation-induced apoptosis of M1p53ts
      (p53val135) cells at the non-permissive temperature; this effect was correlated
      with acceleration of exit from the G2 checkpoint of the cell cycle. In this work
      it is shown that the ability of mutant p53val135 to accelerate irradiation
      induced apoptosis, at the non-permissive temperature, was devoid of
      transcriptional trans-activation of p53 target genes. In contrast, the apoptotic
      function of wt p53val135 was observed to include components which are both
      dependent and independent of transcriptional trans-activation. Taken together,
      these observations suggest that mutant p53val135 protein retains the apoptotic
      component of wt p53 that is devoid of transcriptional trans-activation, and that,
      although this activity is insufficient to induce apoptosis on its own, it can
      cooperate to accelerate DNA damage-induced cell death. The results of this work
      contribute to a better understanding of the complexity of the apoptotic response
      elicited by wt p53, and highlight the potential role of mutant p53 proteins, as
      well as trans-activation independent apoptosis, in tumor suppression by
      irradiation therapy.

PMID- 9625812
TI  - Construction of phosphorylatable chimeric monoclonal antibody CC49.
AB  - Phosphorylation sites were introduced into chimeric monoclonal antibody CC49 (MAb
      chCC49) by inserting synthetic fragments encoding two and six phosphorylation
      sites into an expression vector, pdHL7. The phosphorylation sites were created by
      using the predicted consensus sequences for phosphorylation by the cAMP-dependent
      protein kinase to the carboxyl terminus of the heavy chain constant region of the
      MAb-chCC49. The resultant modified antibodies (MAb-chCC49K1 and MAb-chCC49-6P)
      were expressed in NS0 cells and purified. The MAb-chCC49K1 protein contains two
      phosphorylation sites per heavy chain whereas the MAb-chCC49-6P protein contains
      six sites per heavy chain. Both MAb-chCC49K1 and MAb-chCC49-6P proteins can be
      phosphorylated by the catalytic subunit of cAMP-dependent protein kinase with
      [gamma-32P]ATP to high specific activity. The 32P-labeled MAb-chCC49K1 and MAb
      chCC49-6P proteins bind to cells expressing TAG-72 antigens. The introduction of
      phosphorylation sites into a monoclonal antibody provides a reagent for the
      diagnosis and treatment of cancer. The use of multiple phosphorylation sites
      provides antibodies with very high specific radioactivity and demonstrates that
      cassettes of phosphorylation sites can be introduced into proteins without
      altering their functional activity.

PMID- 9625813
TI  - Tailored therapy for aggressive non-Hodgkin's lymphoma: results of a phase II
      study with a long-term follow-up.
AB  - Aim of the study was to improve cure rate and survival of aggressive non
      Hodgkin's lymphoma (NHL) with a tailored program of therapy based on histologic
      type, prognostic characteristics of patients and response to therapy, and with
      the use of differentiating or cytostatic agents such as Ara-C at low doses and
      alphaIFN. Fifty-four consecutive patients with aggressive NHL were treated in the
      induction phase with 4 sequential courses of a third generation regimen (modified
      CODBLAM IV), followed in responsive patients by 1 cycle of doxorubicin and
      cyclophosphamide and 1 cycle of high dose methotrexate with folinic acid rescue
      (AC-MTX). Patients who achieved partial response (PR) were treated with the
      combination of CCNU + vinblastine if affected by high grade NHL, or with low dose
      Ara-C plus alphaIFN if affected by intermediate grade NHL. Patients who obtained
      complete response (CR) with basal adverse prognostic factors were treated with
      alphaIFN as maintenance therapy for two years. Radiotherapy and surgery were
      effected in selected cases. Thirty-four patients (62.9%) achieved CR and 12
      patients (22.2%) showed PR after induction therapy. Among the 12 patients who
      achieved PR, 6 prolonged CRs were obtained in 7 patients treated with Ara-C at
      low doses plus alphaIFN and 4 CRs were obtained in 5 patients treated with CCNU +
      vinblastine. After completion of treatment, 44 patients (81.5%) obtained CR, 2
      patients (3.7%) showed PR and 8 patients (14.8%) presented progression of disease
      (PD). Fifteen patients received alphaIFN as maintenance therapy. The overall
      survival and failure-free survival rates are 53.7% and 50% respectively, with a
      median follow-up of 82 months: 27 patients remain alive, disease-free without
      relapses, and can be considered cured. This tailored program of therapy resulted
      effective and moderately toxic and may improve the outcome in aggressive NHL.

PMID- 9625814
TI  - Does a relationship exist between trends in estrogen receptor levels and breast
      cancer incidence and mortality?
AB  - Estrogen receptor data from 4,049 patients with primary breast cancer treated at
      the National Cancer Institute of Naples between 1984 and 1996, have been
      evaluated to analyze temporal trend of this tumor marker. The prevalence rate of
      estrogen receptor levels falls from >75% in women older than 60 years to <70% in
      younger patients. The analysis of these data by birth cohort shows a trend very
      similar to that of breast cancer incidence in Italy, suggesting that the breast
      cancer appearance could be modulated in different period of life.

PMID- 9625815
TI  - Regulation of insulin-like growth factor (IGF) II and IGF binding protein 3
      autocrine loop in human PC-3 prostate cancer cells by vitamin D metabolite
      1,25(OH)2D3 and its analog EB1089.
AB  - Prostate cancer and benign prostate hyperplasia (BPH) are major public health
      problems. Prostate epithelial cell proliferation is regulated by insulin-like
      growth factor I (IGF-I) which is mitogenic and anti-apoptotic, and IGF binding
      protein 3 (IGFBP-3) which is an apoptotic agent in these cells. We demonstrate
      that the 1,25(OH)2D3 and its analog EB1089-induced growth inhibition was
      associated with increased IGFBP-3 mRNA abundance, IGFBP-3 mRNA stability, IGFBP-3
      protein accumulation, and decreased IGF-II gene expression. Anti-IGF-II antibody
      and exogenous recombinant human IGFBP-3 inhibit PC-3 cell proliferation. The
      results document the inhibitory effects of 1,25(OH)2D3 and EB1089 on the IGF
      system of mitogens in prostate cancer cells, and suggest a potential therapeutic
      use of EB1089 in treatment of BPH and prostate cancer.

PMID- 9625816
TI  - Synergistic anti-tumor effect of 13-cRA and IFN-alpha/beta in mouse renal cell
      carcinoma.
AB  - The synergistic anti-tumor effect of 13-cis retinoic acid (13-cRA) and interferon
      alpha/beta (IFN-alpha/beta) was investigated using a highly metastatic mouse
      renal cell carcinoma cell subline (RenCa/F). Although 13-cRA inhibited tumor
      growth in vivo as well as in vitro, IFN-alpha/beta did not. Combined
      administration of 13-cRA and IFN-alpha/beta significantly enhanced the anti-tumor
      effect of 13-cRA. The retinoic acid receptor (RAR)-alpha and RAR-gamma were
      expressed in RenCa/F cells. Treatment with IFN-alpha/beta did not influence the
      expression level of these receptors at the mRNA level, which suggests that the
      synergism of 13-cRA and IFN-alpha/beta is not mediated through the RAR.

PMID- 9625817
TI  - DNA methylation in urological malignancies (review).
AB  - Three different kinds of alterations in DNA methylation have been observed in
      urological malignancies. DNA hypermethylation of CpG-rich promoter regions is an
      important mechanism involved in the inactivation of tumor suppressor and other
      genes in prostate, renal cell, and bladder carcinoma. Genome-wide hypomethylation
      is most pronounced in urothelial carcinoma, but also occurs in prostatic cancer.
      Loss of imprinting may be a primary event in the aetiogenesis of Wilms' tumor and
      probably contributes to testicular cancer. With respect to alterations in DNA
      methylation three tumor categories are distinguished: in the development of
      embryonic tumors, e.g. Wilms' tumor, loss of imprinting is important probably by
      upsetting the balance between genes promoting or inhibiting proliferation. In
      tumors with faulty DNA methylation, e.g. renal cell carcinoma, occasional errors
      in DNA methylation are selected for during tumor development. In tumors with
      deranged methylation, e. g. in most bladder and prostate carcinomas, the
      mechanisms establishing methylation patterns are fundamentally disturbed and
      multiple alterations in DNA methylation are observed. At least one of the enzymes
      establishing methylation patterns, viz. DNA methyltransferases and demethylases,
      may be deregulated. Moreover, changes in methyl group metabolism need to be
      considered. DNA hypermethylation and loss of imprinting act by altering the
      expression of selected genes, whereas hypomethylation may facilitate
      transcription and recombination throughout the genome by its effect on the
      chromatin structure. The combination of all three types of alterations may create
      genomic instability in tumors with deranged DNA methylation. Regarding a
      potential clinical use, detection of hypermethylation appears most promising in
      cancer diagnosis, while parameters reflecting genome-wide hypomethylation may
      prove useful in the prediction of prognosis. Inhibitors of DNA methylation are
      being improved and will presumably first be employed against tumors with
      hypermethylated key tumor suppressor genes.

PMID- 9625818
TI  - Enhanced hepatocyte growth factor level in human prostate cancer treated with
      endocrine therapy.
AB  - Hepatocyte growth factor (HGF) has been revealed to have various functions such
      as regeneration, cancer invasion and tumor suppression in normal and cancer cells
      of different organs. To compare HGF expression in non-malignant prostate tissues
      and prostate cancers pretreated with or without neoadjuvant endocrine therapy
      (pretreated PC and non-treated PC), the amounts of HGF protein and mRNA were
      quantitated by Western blot analysis and reverse transcription-competitive
      polymerase chain reaction. The biologically active HGF (baHGF), which was
      converted by an HGF activator protein from secretory type proHGF, showed
      significantly higher expression in pretreated PC than in non-treated PC. The
      amounts of baHGF in pretreated PC were similar to those in non-malignant prostate
      tissues. There was no difference in the expression level of full-length HGF mRNA
      encoding secretory type HGF among the three groups. No variance of tissue content
      of short variant HGF mRNA encoding a competitive HGF antagonist among the three
      groups indicated that short variant HGF protein in prostate cancer seemed not to
      function similarly to a competitive HGF antagonist in benign prostate tissues.
      These results suggest that the tissue level of baHGF in non-treated and
      pretreated PC depends on activation of proHGF supplied from distal organs rather
      than de novo HGF mRNA synthesis in prostate glands. Increased baHGF in pretreated
      PC is expected to relate to tumor suppression in vivo.

PMID- 9625819
TI  - A region on the long arm of chromosome 16 is frequently deleted in metastatic
      node-negative breast cancer.
AB  - The aim of the present study was to define which region of chromosome 16q is most
      relevant for evaluation of the risk of metastatic recurrence in human breast
      cancer cases that are lymph node-negative at the time of diagnosis. For this
      purpose we examined 36 cases of sporadic breast carcinoma subdivided into 3
      groups: the first group: no metastatic progression after an average follow-up
      time of 15 years; including patients with and without lymph node metastases at
      the time of diagnosis; the second group: N+ (node-positive) patients only,
      developed metastasis in five years from surgical excision. The last group was
      composed of patients who developed metastasis but were N0 (node-negative) at
      diagnosis. A statistically significant association was found between LOH (loss of
      heterozygosity) at 16q and metastatic progression of the neoplastic disease. 16q
      LOH was identified as a new independent molecular marker of progression for tumor
      N0 at diagnosis.

PMID- 9625820
TI  - Adeno-associated virus vector mediated transduction of primary normal human
      breast epithelial cells.
AB  - Cultured human breast epithelial cells from reduction mammoplasty specimens were
      transduced using an adeno-associated virus vector encoding the marker gene E.
      coli -galactosidase. Subconfluent, growing, breast epithelial cells were more
      easily transduced than confluent, quiescent, cells. Transduction of non-dividing
      confluent cells could be greatly increased by ultraviolet light-induced DNA
      damage or by prior exposure to the DNA synthesis inhibitor hydroxyurea. The
      effects of ultraviolet light and hydroxyurea on transduction were additive when
      these agents were applied together.

PMID- 9625821
TI  - Immortalization of human oral keratinocytes is associated with elevation of
      telomerase activity and shortening of telomere length.
AB  - Telomerase is a ribonucleoprotein complex that synthesizes TTAGGG repeat
      sequences at the ends of mammalian chromosomes. Its activity is found in most
      cancer cells and few rare normal somatic cells. To investigate whether telomerase
      activity and telomere length of normal human oral keratinocytes (NHOK) are
      altered by <high risk> human papillomaviruses (HPV), we transfected primary NHOK
      with type 16 HPV (HPV-16) genome and determined the activity of telomerase. HPV
      transfection extended the life span of NHOK and eventually induced
      immortalization of cells. Moderate telomerase activity was consistently observed
      in rapidly proliferating NHOK, and activity was not changed in HPV-16 transfected
      cells with extended life span. However, the activity was sharply increased when
      cells passed the crisis stage. Telomere length, which remained constant at
      approximately 6.8 kb during serial passages of NHOK, progressively shortened in
      HPV DNA transfected cells during the period of extended life span and continued
      until crisis, after which it stabilized at approximately 5 kb. These results
      demonstrate that immortalization of NHOK with HPV-16 DNA is associated with the
      activation of telomerase.

PMID- 9625822
TI  - Immunohistochemical localization of metallothionein in hepatocellular carcinoma:
      preferential expression in non-cancerous cirrhotic nodules.
AB  - Metallothionein (MT), an oncofocal gene product was strongly expressed in 35%-95%
      of hepatocytes in hepatocellular carcinoma (HCC) and MT-positive hepatocytes were
      localized mainly in the non-cancerous cirrhotic nodules but not in malignant
      hepatocytes. On the other hand, <10% hepatocytes showed weak staining for MT in
      chronic hepatitis and cirrhosis of liver. Strong expressions of MT in non
      cancerous cirrhotic nodule in HCC and low expressions in liver cirrhosis without
      HCC indicate a relationship between malignant transformation of hepatocytes and
      the expression of MT.

PMID- 9625823
TI  - Clinicopathologic and immunohistochemical analyses in lung metastasis of
      colorectal carcinoma.
AB  - We compared the immunohistochemical staining patterns of carcinoembryogenic
      antigen (CEA), CA19-9 and proliferating cell nuclear antigen (PCNA) between
      specimens from 13 patients who had undergone surgery for colorectal carcinoma
      with lung metastasis (lung metastasis group) and specimens from 13 patients who
      had no evidence of recurrence or metastasis within at least 5 years after
      colorectal resection (no metastasis group). The PCNA labeling indices of primary
      and metastatic lesions were 53.29 8.88% and 63. 26 6.21% (p<0.001), respectively.
      The PCNA labeling index in the no metastasis group was 26 12.9% (p<0.001). There
      was no significant difference in the CA19-9 staining patterns between the two
      groups. The CEA distribution patterns in the primary and lung metastatic lesions
      were different even in the same case. The original tumor cells showed apical or
      C1 localization, whereas metastatic cells showed C2 localization. These findings
      indicate that patients having colorectal carcinoma with a high PCNA labeling
      index have a high probability of lung metastasis, and that the CEA distribution
      pattern would change after original tumor resection.

PMID- 9625824
TI  - Hepatocyte growth factor and Met/HGF receptors in patients with gastric
      adenocarcinoma.
AB  - Overexpression and amplification of Met/HGF receptor has been detected in gastric
      cancer tissues and cell lines. In this study hepatocyte growth factor (HGF) and
      Met/HGF receptors were localized in 32 gastric cancer and adjacent normal gastric
      tissues by the avidin-biotin-peroxidase complex technique. HGF (87.5%) and
      Met/HGF receptors (68.8%) were demonstrated in gastric cancer tissues. A high
      positive rate of HGF (87.0%) and Met/ HGF receptors (82.6%) presented in
      intestinal type gastric cancer. HGF immunoreactivity in gastric cancer tissues
      was a significant and powerful prognostic indicator (relative risk 15.9; p=0.01).
      These data suggest that HGF and Met/HGF receptors are involved in the
      morphogenesis of intestinal type gastric cancer. HGF may have other mechanism
      that favor gastric cancer spread and independently affect survival.

PMID- 9625825
TI  - Immunisation of colorectal cancer patients with autologous tumour cells.
AB  - Patients with colorectal cancer were entered into a clinical phase I trial of
      immunotherapy with an autologous tumour cell/bacillus Calmette-Guerin (BCG)
      vaccine. We attempted to describe the possible effects and side effects of the
      immunisation, and further to investigate whether expression of immune-response
      related surface molecules on the tumour cells in the vaccine correlated with
      survival. The first and second vaccine comprised of 107 irradiated tumour cells
      mixed with BCG, the third of irradiated tumour cells only. Thirty-nine patients
      were considered, but only 6 patients fulfilled the criteria for inclusion. No
      serious side effects were observed. With three years of observation time, two
      patients are healthy, while the rest have had recurrence, and two of them have
      died. In all vaccines, all tumour cells expressed HLA class I, some expressed HLA
      class II and none expressed CD80. There was an inverse relation between survival
      and HLA class II expression. This highlights an essential problem, in the absence
      of CD80 expression the expression of HLA class II may induce anergy. In future
      attempts to develop improved vaccines this problem should be addressed.

PMID- 9625826
TI  - Effect of the nitrosourea anti-tumor chemotherapeutical agent MCNU on five human
      myeloma cell lines.
AB  - We investigated the effects of MCNU (methyl-6)3-(2-chloroethyl)-3-nitrosoureido)
      6-deoxy- alpha-D-glucopyranoside), a nitrosourea anti-tumor agent developed in
      Japan, on cell growth and differentiation in five human myeloma cell lines and
      compared it with relative expression levels of MDR-1 gene. Although 10 microg/ml
      of MCNU inhibited cell growth in KMM-1 and KMS-5 lines, other three cell lines
      required 20-40 microg/ml of MCNU to obtain similar growth inhibition.
      Accumulation up to the G2 phase of the cell cycle was observed in KMM-1 and KMS-5
      lines and the cloning efficiency of KMS-5 cells was reduced by MCNU. On the other
      hand, expression of surface markers on these lines was not altered remarkably
      except for increased expression of CD38 on KMS-5 cells. However, the effect of
      MCNU on these cell lines did not correlate to relative expression levels of MDR-1
      gene analyzed by RT-PCR. MCNU may inhibit the growth of myeloma cells by the
      accumulation of these cells up to the G2 phase, but may not affect their
      differentiation.

PMID- 9625827
TI  - A case of biliary cystadenoma with obstructive jaundice.
AB  - Biliary cystadenoma is a rare cause of obstructive jaundice. We report a case of
      a 78-year-old Japanese man with biliary cystadenoma presenting repetitive
      abdominal pain and jaundice. Ultrasound sonography revealed a hyperechoic mass in
      the left lateral lobe of the liver. Histological examination revealed a biliary
      cystadenoma. Intracystic hemorrhage was assumed to be the cause of obstruction of
      the bile ducts.

PMID- 9625828
TI  - Effects of azoxymethane on X-ray induced intestinal metaplasia in Donryu rats.
AB  - The present study was undertaken to determine the effect of azoxymethane (AOM)
      administration on intestinal metaplasia induced by X-irradiation in male Donryu
      rats. Five-week-old animals were X-irradiated with two doses of 10 Gy each at a 3
      day interval or three X-ray doses of 10 Gy at a 2-day interval and then received
      AOM injections i.m. at a dose of 15 mg/kg body weight once weekly for 3 weeks, 6
      months after irradiation. Alkaline phosphatase positive foci were decreased after
      AOM treatments, but aberrant crypt like-foci appeared within areas of intestinal
      metaplasia. In contrast no induction was observed in normal-appearing gastric
      mucosa.

PMID- 9625829
TI  - Low-grade malignant tumors of the lung: is lymph node dissection necessary?
AB  - Low-grade malignant tumors (LGMT) of the lung were surgically treated in our
      institute between 1981 and 1997. Both the characteristics and prognosis were
      examined. We studied 10 cases with LGMT of the lung, male to female ratio 1:1,
      age range 15 to 71 years, mean 55 years, 6 central and 4 peripheral. Five
      patients had lobectomy, 3 had sleeve lobectomy and 2 had bilobectomy.
      Pathologically, 5 samples were typical carcinoid, 3 were mucoepidermoid carcinoma
      and 2 were adenoid cystic carcinoma. None of the patients had lymph node
      metastasis. Nine patients were stage I and one stage IIIA. Seven patients
      underwent absolutely curative resection; 2, relatively non-curative resection; 1,
      non-curative resection. In preoperative examination, only 4 patients was
      diagnosed correctly and the others were misdiagnosed. Mean survival time was
      167.5 months. One patient died from causes other than the primary cancer and the
      others are surviving (range 2-173 months). The LGMT group was significantly
      younger and had a significantly better prognosis compared with the control group
      (p=0.02). Mediastinal lymph node dissection is suggested to be omitted. However,
      further accumulation of cases is necessary regarding to the omission of lymph
      node dissection.

PMID- 9625830
TI  - The elevated mRNA content as a potential indicator of precancerous states of the
      gallbladder mucosa in patients with pancreaticobiliary maljunction.
AB  - Pancreaticobiliary maljunction (PBM) patients have a high incidence of cancer in
      the gallbladder. In the present study, we showed that precancerous lesions in the
      gallbladder of PBM such as hyperplasia or metaplasia, indicated high
      concentration of the amount of total mRNA. The mRNA content could be easily
      measured by our new technique utilizing a GenePlate, which is a poly (dT)
      oligonucleotide immobilized plastic plate, and Yoyo-1, a fluorescent DNA
      intercalator. To standardize the mRNA contents, we utilized <mRNA index> which
      was defined as the ratio of total mRNA contents to total nucleic acids in a same
      sample. The mRNA index of the proliferating cells was significantly higher than
      that of the resting cells, and the mRNA index of cancer cells, such as gastric
      cancer, colon cancer, bile duct cancer, and gallbladder cancer also showed
      significantly higher concentration than that of normal mucosa. In the study of
      precancerous lesion, PBM, the mRNA index was significantly higher than that of
      mild cholecystitis but less than that of gallbladder cancer, suggesting that in
      the gallbladder mucosa of PBM, a precancerous state was able to be diagnosed by
      the mRNA index.

PMID- 9625831
TI  - Relapse of pulmonary Mycobacterium kansasii disease associated with large-cell
      cancer of the lung: a case report.
AB  - A 43-year-old caucasian male diabetic presented with purulent cough and a history
      of weight-loss, elevated temperature, night-sweat and dyspnea. Four years
      previously, the patient had undergone a 12-month antimycobacterial regimen
      because of pulmonary mycobacterium kansasii (MK) disease of the left upper lobe
      (LUL). Treatment had led to complete recovery with the exception of minor fibrous
      residuals in the involved pulmonary segments. Chest radiograph and computed
      tomography (CT), performed on recent admission, revealed a dense infiltration of
      these residual-containing segments. Microbiological evaluation of bronchial
      brushings, aspirates and histology of the transbronchial biopsies indicated a
      relapse of pulmonary MK disease. Although antimycobacterial treatment was started
      immediately, therapeutic effects were only minimal and remained to be limited to
      the initial phase of the treatment. After four weeks of treatment, the patient's
      general condition worsened again. Follow-up CT of the lung showed a marked
      increase of the infiltration in the left apicoposterior lobe and re-bronchoscopy
      showed a tumorous protrusion of the bronchial wall involving the apicoposterior
      segment ostium, a finding which was not seen in the previous bronchoscopy.
      Histology of the transbronchial biopsies revealed a carcinoma mainly from large
      cell type.

PMID- 9625832
TI  - Anhydroretinol, a retinoid active in preventing mammary cancer induced in rats by
      N-methyl-N-nitrosourea.
AB  - As determined by in vitro tests, anhydroretinol, a metabolic product of retinol,
      was bound specifically by serum retinol-binding protein and by cellular retinol
      binding protein but not by cellular retinoic acid-binding protein or the nuclear
      receptors, RARs and RXRs. For rats dosed with the mammary carcinogen, N-methyl-N
      nitrosourea (45 mg/kg body weight) and given diets containing either the retinoid
      vehicle, anhydroretinol (67, 134, 268, or 536 mg/kg of diet), or retinyl acetate
      (328 mg/kg of diet), there were, over a 90-day observation period, no significant
      differences in body weights. The compound did not accumulate in liver tissue or
      cause an increase in hepatic levels of retinyl palmitate (potential problems
      observed with other retinoids). The numbers of mammary cancers were as follows:
      no retinoid, 4.5/rat; retinyl acetate, 2.1/rat; and increasing doses of
      anhydroretinol, 2.9, 3.3, 3.0, and 1.7/rat, respectively. Thus, anhydroretinol,
      at non-toxic levels, was effective as a preventive agent in this experimental
      model of breast cancer.

PMID- 9625833
TI  - A clinicopathologic study of the resected cases of adenosquamous carcinoma of the
      lung.
AB  - Ten cases of surgically resected adenosquamous carcinoma of the lung were studied
      clinicopathologically, and their outcome was compared with that of
      adenocarcinomas and squamous cell carcinomas of the lung. The frequency rate of
      adenosquamous carcinoma was 1.5% of 668 primary lung cancers resected in our
      hospital. The survival curves of patients with adenosquamous carcinomas,
      adenocarcinomas, and squamous cell carcinomas indicated that the outcome of
      adenosquamous carcinoma was statistically poorer than that of adenocarcinoma
      (p=0. 01), and tended to be poorer than that of squamous cell carcinoma
      (p=0.051). The amount of adenocarcinoma component did not affect the survival
      rate. Five-year survival was not obtained in this series. Although our series is
      small, this study suggests that adenosquamous carcinoma of the lung is an
      aggressive tumor with poor prognosis.

PMID- 9625834
TI  - Ki-67 antigen expression in relation to clinicopathological variables and
      prognosis in gastric cancer.
AB  - One hundred and thirty surgical specimens of gastric adenocarcinoma were obtained
      from patients who had undergone radical gastrectomy. The samples were formalin
      fixed, paraffin-embedded and used for immunostaining of Ki-67 antigen. Mean Ki-67
      index was 41.8% (SD 15. 7%, range 8.2-84.2%). Differentiated carcinomas had a
      higher Ki-67 index than undifferentiated tumors, although other
      clinicopathological variables, including lymph node metastasis and depth of
      invasion showed no correlation with Ki-67 index. In the undifferentiated tumors,
      Ki-67 index correlated with lymph node involvement. A high Ki-67 index ( 55%) was
      found to be an independent indicator of poor prognosis in patients with
      undifferentiated tumors.

PMID- 9625835
TI  - Detection of serum p53 antibodies in patients with esophageal squamous cell
      carcinoma: correlation with clinicopathologic features and tumor markers.
AB  - The significance of serum p53-Abs in patients with esophageal squamous cell
      carcinoma was determined. Examination of clinicopathological features and
      assessment of tumor marker sensitivities of carcinoembryonic antigen (CEA),
      squamous cell carcinoma antigen (SCC-Ag) and CYFRA21-1 were performed. Thirty
      three (58%) of 57 patients were positive for serum p53-Abs, however, no relation
      with cancer progression existed. Fourteen of the 33 sero-positive patients
      revealed normal levels of all tumor markers tested. Thus, serum p53-Abs appears
      to be a useful marker for the detection of esophageal squamous cell carcinoma.

PMID- 9625836
TI  - Different expression patterns of MMP-2 and MMP-9 in breast cancer.
AB  - Among the many biological characteristics of cancer, the matrix metalloproteinase
      (MMPs) is essential for tumor invasion and metastasis. The relationship between
      MMP-2 and MMP-9 according to tumor progression has not been studied yet. We
      evaluated the synchronous expression and activation rate of MMP-2 and MMP-9 in
      breast cancer tissues and compared them to the clinical parameters in order to
      determine the clinical significance of MMPs and the possibilities of using them
      as a therapeutic target. The activity of MMPs was evaluated in 121 breast cancer
      tissues using zymography and the area of activation was calculated by computer
      assisted densitometry in comparison to the activity of a positive control (HT
      1080). In 121 tumor tissues, 32 (26.4%) did not express any form of MMPs and 19
      (15.7%) showed both expression of MMP-2 and MMP-9. We observed that only one
      tissue expressed MMP-9 alone, while MMP-2 alone was expressed in 69 tissues. In
      88 patients with MMP-2 and/or MMP-9 expression, we were unable to observe any
      correlation between the activity of MMPs expression or activation rate and the
      clinical parameters. But MMP-2 and MMP-9 activity increased according to T
      factor. Rapid production of MMP-9 occurred from T2 (p=0.046), while that of MMP-2
      occurred from T3 (p=0.004). In conclusion, MMPs activity was organ specific. The
      major MMPs in breast cancer was MMP-2 and MMPs activity was different with tumor
      progression. When MMPs are a specific therapeutic target, we should use different
      inhibitors according to tumor size, in patients at the same stage.

PMID- 9625837
TI  - A pilot study of nedaplatin and etoposide for recurrent gynecological
      malignancies.
AB  - Nedaplatin is a new analogue of cisplatin with similar efficacy but less renal
      toxicity. We assessed the efficacy and toxicity of nedaplatin and etoposide for
      recurrent gynecological malignancies. Eight patients were treated with 100 mg/m2
      of nedaplatin (day 1) and 70 mg/m2 of etoposide (days 1, 3, and 5 ) every 4
      weeks. A total of 17 courses was given. Grade 3/4 leucopenia and thrombocytopenia
      occurred, but was manageable. The response rate was 37.5% (partial response n=3;
      no change n=4; progressive disease n=1). In conclusion, a phase II study of this
      regimen for recurrent gynecological malignancies is warranted.

PMID- 9625838
TI  - Time elapsing from cancer diagnosis and anxiety in women attending cancer genetic
      clinics.
AB  - The aim of this study was to investigate the effects of cancer genetic
      consultations on feelings of anxiety in women with breast/ovarian cancer. Among
      the 138 women attending six French clinics during a one-year period, 115 (83.3%)
      answered pre- and post-consultation questionnaires. The state anxiety score
      (Spielberger's STAI) was lower (paired t-test, p<0.001) after the consultation
      (34.7 9.4) than before (38.8 10.5). The time elapsing since cancer diagnosis (r=
      0.28, p=0.007) was the main predictor of the decrease in anxiety. The patients
      consulting earlier after their cancer was diagnosed were more anxious before the
      consultation than those consulting later: whereas their anxiety states after the
      consultation were similar. The consultation effectively decreased the anxiety
      observed and the anxiety felt by cancer patients before the consultation may
      constitute an anticipatory stress response that should be investigated.

PMID- 9625840
TI  - A phase II study of bromocriptine in patients with androgen-independent prostate
      cancer.
AB  - Prolactin is an important physiological regulator of prostate development and
      growth in preclinical models. In prostate cancer there is strong evidence that
      prolactin exerts a trophic effect independent of testosterone. In addition,
      patients with prostate cancer that have an elevated prolactin level correlated
      with a poorer prognosis. Based on these data, we evaluated the clinical effect of
      prolactin suppression using bromocriptine in patients with androgen-independent
      prostate cancer. We conducted an open-label phase II trial of bromocriptine in
      patients with progressive metastatic prostate cancer. Basal and thyrotropin
      releasing hormone (TRH)-stimulated prolactin levels were utilized as biological
      endpoints for determining the dose of bromocriptine. All patients continued to
      receive complete androgen blockade. Thirteen patients were enrolled (median age
      69.5 years). There were no complete or partial responses associated with
      bromocriptine in 11 of the evaluable patients. The mean duration of bromocriptine
      treatment was 8.2 weeks (2-14 weeks). One patient had a clinically insignificant
      decrease in prostate-specific antigen (PSA) and another patient had a 19.9%
      decrease in PSA with progression of a soft tissue mass. The vast majority of
      patients (10 of 11) had suppression of prolactin with a bromocriptine dose of 2.5
      mg three times a day. One patient required a dose adjustment due to inadequate
      suppression, with a final maintenance dose of bromocriptine 12.5 mg per day
      resulting in complete suppression. No serious treatment-related toxicities were
      observed. The most common complications noted were nausea, headaches, dizziness,
      and fatigue. Our data showed that 2.5 mg three times per day of bromocriptine
      suppressed prolactin in 90% of the patients. Furthermore, this dose appears to be
      well tolerated.

PMID- 9625839
TI  - The effect of amiloride on the metastatic properties of prostate cancer in the
      Dunning rat model.
AB  - Most deaths from cancer result from the metastatic spread of the disease. The
      antidiuretic amiloride has been shown to inhibit tumor growth and metastasis in
      several tumor systems. The object of these studies was to examine the effect on
      the in vitro and in vivo tumor growth and metastasis in the MatLyLu subline of
      the Dunning model of rat prostate cancer. In vitro, amiloride was found to have
      cytotoxic effects only at high concentrations, with an IC50 of 100 microg/ml. In
      vitro analysis of the ability of amiloride to inhibit invasion of MLL cells
      demonstrated that this drug was ineffective at all concentrations examined. In
      vivo, amiloride did not inhibit tumor growth or metastases development. Our
      studies demonstrate that amiloride does not have activity in this model of
      prostate cancer and suggest it may not be an appropriate therapy for the
      treatment of prostate cancer.

PMID- 9625841
TI  - First line chemotherapy in patients with brain metastases from non-small and
      small cell lung cancer.
AB  - In this study we evaluated the role of systemic chemotherapy in 23 previously
      untreated patients with brain metastases from both non-small cell lung cancer
      (NSCLC) and small cell lung cancer (SCLC). In NSCLC group, 2 patients out of 14
      had a brain response after treatment (1 complete and 1 partial response). In the
      group of 9 patients with SCLC, we observed 5 brain responses (3 complete and 2
      partial responses). Brain responses were in accordance with extracranial
      responses although this appeared more clearly in SCLC than in NSCLC patients.

PMID- 9625842
TI  - Variable levels of bcl-2, bcl-x and bax mRNA in bladder cancer progression.
AB  - We investigated the expression of the anti-apoptotic genes bcl-2 and bcl-X and
      the pro-apoptotic gene bax in bladder tumors and normal samples from urinary
      bladder, using RT-PCR analysis. Bcl-2 mRNA was not detected in any of the normal
      samples, while it was found expressed in 66% of the low stage tumors and in 100%
      of the high stage tumors. Bax expression had an inverse progress, being present
      in 62% of the normal tissues examined, in 16% of the low stage tumors and in 14%
      of the high stage. Bcl-X gene expression was quite variable among all samples
      (37% in normal tissues, 50% in the low stage tumors and 14% in the high stage).
      bcl-X mRNA was only found in the isoform bcl-XL, with anti-apoptotic functions,
      whereas no sample expressed the isoform bcl-XS, which is known to suppress bcl-2
      functions. Most samples expressing bcl-2 did not express bcl-X, and vice versa.
      These results, besides confirming the potential role of these genes in the
      pathogenesis of low stage bladder cancer strengthen the hypothesis concerning
      their possible interaction in the progression of disease.

PMID- 9625843
TI  - Epidemiological aspects of cutaneous malignant melanoma (review).
AB  - There is an increasing interest in the etiology of cutaneous malignant melanoma
      (CMM). Once considered a rare tumour, CMM is now the fourth commonest cancer in
      Australia and New Zeland, the tenth in the Usa, Canada and Scandinavia and the
      eighteenth in Great Britain. The growing scientific concern on the urgent need to
      highlight the cause/s of CMM is well documented by the large number of well
      designed and well-conducted epidemiological studies reported in the last two
      decades. Such studies facilitated testing of many etiological hypotheses derived
      from earlier descriptive investigations and contributed to significant progress
      in understanding the etiology of such disease. The quantification of the extent
      to which the increases in CMM incidence and mortality rates are related to new
      lifestyles and to new patterns of exposure to potential carcinogenetic agents is
      essential in order to establish an appropriate preventive strategy. In population
      of mainly European origin a substantial proportion of the increased incidence of
      CMM is attributable to steady change from predominantly occupational to
      predominantly recreational exposure to solar radiation. Therefore the present
      review puts particular emphasis on exposure to sunlight as well as to artificial
      ultraviolet light, as modifiable causes of CMM. Incidence and mortality data and
      other potential risk factors for the development of CMM will also be briefly
      reviewed.

PMID- 9625844
TI  - A methylenetetrahydrofolate reductase polymorphism is associated with expression
      of p16 in human lung cancer.
AB  - Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in the folate
      cycle. Reduced MTHFR activity induces DNA hypomethylation and stability, which
      may protect the tumor suppressor gene p16INK4. We examined the association
      between MTHFR polymorphism and expression of p16INK4. The frequency of the MTHFR
      genotypes were 21 Ala/Ala, 29 Ala/Aal, and 7 Val/Val. Expression of p16INK4 was
      26.2 +/- 26.8% in the Val/Val genotype and 11.2 +/- 16.6% in the other genotypes
      (p=0.46) as examined by immunostaining, and excluding four specimens that were
      overstained. These results suggest that folate metabolism can affect
      carcinogenesis through the expression of p16INK4.

PMID- 9625846
TI  - The effect of hydrazine sulfate on prostate cancer growth.
AB  - Prostate cancer remains the most commonly diagnosed cancer in American males and
      is the second leading cause of cancer death in this group. Hydrazine sulfate, an
      inhibitor of gluconeogenesis, has been proposed as a means to improve nutritional
      status and improve survival in patients with solid tumors. We investigated the
      effects of hydrazine sulfate on both in vitro and in vivo models of prostate
      cancer. We examined the cytotoxicity of hydrazine sulfate in both human (LNCaP
      and PC-3) and animal (MAT-LyLu) prostate cancer cell lines. No growth inhibition
      was observed. In vivo, hydrazine sulfate did not suppress the growth of implanted
      Dunning rat prostate MAT-LyLu cells. Hydrazine sulfate does not have activity in
      these models of prostate cancer and may not be an appropriate therapy for
      patients with prostate cancer.

PMID- 9625845
TI  - Paclitaxel in anthracycline-treated breast cancer patients.
AB  - Between May 1995 and July 1997, paclitaxel (TX) (175 mg/m2 by 3 h i. v. infusion
      every 21 days) was administered to 70 consecutive patients (median age: 57 years)
      previously treated with the FEC regimen (cyclophosphamide and 5-fluorouracil, 600
      mg/m2, plus epirubicin, 60 or 120 mg/m2) as an adjuvant setting or as a first
      line therapy for metastatic disease. Sixty-eight patients were evaluable for
      response, while two died early. Patients received a median of 4.7 (3-12 course)
      of TX for a total of 211 courses. The overall response and stable disease rate
      was 54% in 11 patients, who relapsed following adjuvant FEC, and 60% in 57
      patients, who received FEC as first treatment for their metastatic disease. No
      complete respose was obtained. In patients pretreated for metastatic disease,
      response and stable disease rates were similar irrespective of previous response
      to FEC. Main hematologic toxicity of TX was of short duration, grade II/III
      leukopenia (86% of patients) and non-hematologic toxicity was grade II/III
      peripheral neuropathy, related to the cumulative dose of TX. At this schedule, TX
      offers a significant rate of partial responses or disease stabilization in
      patients with metastatic breast cancer previously treated with FEC.

PMID- 9625847
TI  - Collecting duct carcinomas of the kidney: a comparative loss of heterozygosity
      study with clear cell renal cell carcinoma.
AB  - Origin of collecting duct carcinomas (CDC) of the kidney is not entirely known,
      although it is thought that they originate from the distal collecting duct
      system, whereas clear cell renal cell carcinoma (cRCC) may originate from the
      proximal tubular epithelium. In cRCC, the von Hippel Lindau gene (vHL) is damaged
      in almost 100% of cases; the frequency of vHL deletions in CDC is not known. Loss
      of heterozygosity (LOH) of CDC and cRCC of vHL (3p), p16 (9p), p53 (17p) and the
      retinoblastoma (RB) gene (13q) was studied to evaluate possible genetic
      differences between the two. LOH of the vHL was seen in 77.7% of cRCC and in 55%
      of CDC. P16 was lost in 33% of cRCC and in 50% of CDC. LOH in p53 was observed in
      0/8 cases of cRCC compared to 18.7% in CDC. LOH in 13q was seen in 25% of both
      CDC and cRCC. The high LOH rate of the vHL gene in CDC has not been observed
      previously. The findings indicate that CDC and cRCC share certain genetic
      alterations, including frequent deletion of the vHL gene. CDC is not clearly
      related to cRCC but may be of heterogeneous origin.

PMID- 9625848
TI  - Prognostic value of low density lipoprotein receptor expression in colorectal
      carcinoma.
AB  - Cancer cells require more cholesterol than normal cells. This requirement seems
      to be satisfied by a higher HMG-CoA reductase activity or a higher activity of
      low density lipoprotein receptor (LDLR). We investigated the prognostic value of
      LDLR in colorectal carcinoma (CRC) patients. The LDLR was evaluated in 90
      patients with CRC by ELISA. The survival time and the relative risk of prognostic
      factors were analyzed by Kaplan-Meier estimates and Cox proportional hazard
      model. Thirty three cases were LDLR positive (+), while 57 LDLR negative (-). The
      survival of LDLR(-) patients was shorter than that of LDLR(+). By Cox model, the
      absence of LDLR and time until metastasis resulted significantly associated with
      the CRC-related survival. The absence of LDLR in CRC predicts a shorter survival.

PMID- 9625849
TI  - Single-dose etoposide in advanced pancreatic and biliary cancer, a phase II
      study.
AB  - Palliative chemotherapy can add to the duration and quality of life in patients
      with advanced pancreatic and biliary cancer, albeit in a limited way. Between
      March 1995 and October 1997, 31 symptomatic patients were treated with etoposide
      in a phase II trial. Measurements of objective and subjective responses were
      performed, the latter by the treating physician and with the method of clinical
      benefit response (CBR). Quality of life was evaluated with the EORTC QLQ-C30
      questionnaire. A partial response was seen in 2 (6%) patients. Subjective
      responses/quality of life gains were seen in 6 (19%), 7 (23%) and 9 (29%)
      patients, respectively, with the different methods. Median survival was 4.5
      months. WHO grade 3 and 4 toxicity, alopecia excluded, was seen in 20% of the
      patients. The clinical activity of etoposide is limited, and in the same low
      range as other drugs in these diseases.

PMID- 9625850
TI  - Undiagnosed adult T-cell leukemia/lymphoma in central Brooklyn, NY.
AB  - We present a case, identified by surveillance for adult T-cell leukemia/lymphoma
      (ATL), who had initial symptoms not specifically related to ATL, and who would
      not have been identified as having ATL otherwise. A 51-year-old Trinidadian black
      woman was hospitalized for abdominal pain, nausea, and vomiting. Hematology and
      clinical chemistry revealed leukocytosis (19,600/mm3), an elevated lymphocyte
      percent (63%), and hypercalcemia (19.4 mg/dl). The patient was serologically
      confirmed with HTLV-I-associated ATL. Lymphoma was diagnosed at autopsy. This
      case is representative of ATL, which along with HTLV-I infection, may be emerging
      public health problems in urban communities of the northeast and southeast United
      States.

PMID- 9625851
TI  - Clinicopathologic analysis of mullerian adenosarcoma: the M.D. Anderson Cancer
      Center experience.
AB  - The records of 41 patients diagnosed with adenosarcoma of the female genital
      tract between 1982 and 1996 were reviewed. The median age at diagnosis is 51
      years (range, 14-84). The most common symptom is vaginal bleeding (71%). Clinical
      signs at presentation include pelvic mass (37%), uterine polyps (29%), and
      enlarged uterus (22%). In 71% of patients, the tumor originates from the uterus.
      Other sites include ovary (15%), pelvis (12%), cervix (2%). A history of thyroid
      cancer, benign ovarian cyst, and polycystic ovarian disease is found more
      frequently than expected in this patient population, whereas no relationship to
      endometriosis is observed. Surgery is the mainstay of treatment, but platin-based
      chemotherapy given upfront in inoperable patient has definite efficacy. An
      overall response rate of 92.5% was observed after primary therapy (surgery with
      or without radiotherapy, and/or chemotherapy), with a median survival of 48
      months (range, 1-174). Thirty-eight percent of patients had recurrent disease.
      The median time to recurrence is 12 months (range, 5-132). Although 60% of
      patients with recurrence achieved a complete remission after treatment, only 1
      (8%) is alive without disease, and 3 (22%), with disease at the time of this
      analysis. In our series, histologic sarcomatous overgrowth is a predictor of poor
      prognosis (p<0.03), however myometrial invasion and stage of disease seem to be
      of less prognostic significance. Adenosarcoma is a tumor with a fair prognosis.
      Most tumor can be cured with surgery, but recurrence carries a bad prognosis.

PMID- 9625852
TI  - Early gastric cancer in the province of Forli: follow-up of 337 patients in a
      high risk region for gastric cancer.
AB  - Long-term clinical outcome was analysed in a series of 337 patients with early
      gastric cancer (EGC) at a median follow-up of 8 years. Tumours were classified
      according to the macroscopic and microscopic criteria proposed by the Japanese
      society of gastroenterological endoscopy (JSGE) and Lauren, respectively. Type of
      penetration (PEN) was classified according to Kodama. Overall survival rate was
      92% at 5 years and 88% at 8 years and was significantly related to depth, type of
      penetration, lymph node status and tumour size. A significantly lower 5-year
      survival (p<0.05) was observed for patients with lymph node metastases and PEN A
      type EGC (55%) or for those with node-positive tumours and submucosal wall
      penetration (58%) than for the other pathologic subgroups. Therefore, these two
      subgroups should be considered as advanced gastric cancer patients from the
      prognostic point of view. Moreover, multivariate analysis by Cox regression model
      showed the degree of lymph node involvement and Kodama's type PEN A as the only
      independent prognostic factors.

PMID- 9625853
TI  - Bone tumor radiograph review by pathologists prior to pathologic diagnosis: a
      receiver operator curve analysis of diagnostic utility.
AB  - Radiologic-pathologic correlation has long been considered a prerequisite for the
      accurate diagnosis of bone lesions. We investigated using receiver-operating
      characteristic analysis the accuracy of histopathologic diagnoses with and
      without pathologist review of radiographs. While accuracy of diagnosis did
      improve when the radiographs were reviewed by the pathologist, this increase did
      not reach statistical significance (P=0.1311). Potential reasons for this finding
      including case selection and reviewer expertise are discussed. Based on our
      study, the review of radiographs did not result in a statistically significant
      difference in accuracy of the pathologic diagnosis of bone tumors. However, our
      data suggest that there may be a difference particularly in selected cases and
      among certain observers.

PMID- 9625854
TI  - Basic fibroblast growth factor in serum and urine of patients with head and neck
      cancer.
AB  - Between 1996 and 1997 serum and urine levels of basic fibroblast growth factor (b
      FGF) in patients with head and neck cancer were measured to answer the following
      questions: i) Are increased levels of b-FGF in serum and urine detectable in
      patients with malignant head and neck tumors? ii) Do these parameters correlate
      with tumor stage and differentiation of tumors? iii) Is there an association
      between growth behaviour (local or metastatic growth) and b-FGF levels in serum
      and/or urine? Eighty-nine patients with head and neck cancer as well as 45
      patients with diseases unrelated to cancer were investigated. Detectable levels
      of b-FGF were found in the serum and urine of patients with malignant head and
      neck tumors. In addition, there was a significant correlation between tumor size
      and b-FGF levels in either serum or urine. No association of b-FGF concentrations
      with degree of histologic differentiation and tumor growth behaviour was
      observed. The results of this study demonstrate that b-FGF levels are elevated in
      serum and urine of patients with head and neck cancer. These findings suggest an
      involvement of b-FGF in the formation of solid tumors.

PMID- 9625855
TI  - Effects of dietary anticarcinogens on rat gastrointestinal glutathione peroxidase
      activity.
AB  - Several naturally occurring and synthetic food components reduce gastrointestinal
      cancer. Many of these compounds are scavengers of free radicals, formed during
      oxidative stress. Glutathione peroxidases (GPxs) protect against free radicals by
      catalysing their inactivation, thereby consuming glutathione (GSH). This might be
      one of the mechanisms leading to cancer prevention. We studied the effect of
      several dietary anticarcinogens on gastrointestinal GPx enzyme activities in male
      Wistar rats. Total as well as selenium-dependent and non-selenium-dependent GPx
      (t-GPx, Se-GPx and nSe-GPx) enzyme activities were determined in cytosolic
      fractions of oesophagus, gastric and colonic mucosa and liver. d-Limonene induced
      all three types of GPx activities in the oesophagus. d-Limonene and PEITC induced
      colonic t-GPX and nSe-GPx activity. beta-Carotene induced all three colonic GPx
      activities and hepatic t-GPx and Se-GPx activity. Coumarin and alpha-tocopherol
      induced gastric t-GPx and colonic nSe-GPx activity. Oltipraz enhanced oesophageal
      and gastric t-GPx and oesophageal, gastric and colonic Se-GPx. All other
      anticarcinogens induced one type of GPx activity at one site. In conclusion, the
      specific enhancement of GPx enzyme activities by dietary anticarcinogens might
      lead to a more efficient reduction of organic hydroperoxides and hydrogen
      peroxide and thus add to prevention of carcinogenesis in these organs.

PMID- 9625856
TI  - Modifications in the carcinogen-metabolizing capacity of mouse liver treated with
      N-nitroso compounds.
AB  - One tenth of the LD50 as a single dose of various N-nitroso compounds (N
      nitrosodimethylamine; NDMA, N-nitrosodiethylamine; NDEA, N
      nitrosoethylpropylamine; NEPA, N-nitrosodipropylamine; NDPA, N
      nitrosomethylethylamine; NMEA, N-nitroso-methylbutylamine; NMBA and N
      nitrosoethylbutylamine; NEBA) was administrated into male mice. This dose
      markedly increased the hepatic contents of cytochrome P450 and cytochrome b5 and
      activities of NADPH-cytochrome c reductase and aryl hydrocarbon hydroxylase
      (AHH). The highest increase in the activity of cytochrome P450 (+142% relative to
      the control value) was shown in animals treated with either N
      nitrosoethylpropylamine or N-nitrosodiethylamine. On the other hand, the lowest
      increase in the activity (+16%) was revealed in animals treated with N
      nitrosodimethylamine (not significant compared to the control value). Cytochrome
      b5 content was increased by 190% of the control value in mice treated with N
      nitrosomethylbutylamine, while N-nitrosodibutylamine induced the lowest increase
      (+20%). The maximum increase (+182%) in the activity of aryl hydrocarbon
      hydroxylase was shown in animals which received N-nitrosomethylbutylamine, while
      the lowest increase (+23%) in animals which received N-nitrosodiethylamine. The
      activity of hepatic AHH was also increased above the control value in animals
      treated with NDMA, NEBA NDPA, NMEA and NDBA by 138, 98, 90, 89 and 69%,
      respectively. Identically, NADPH-cytochrome c reductase activity was increased in
      animals which received NEPA, NMBA, NDMA, NMEA, NDPA, NEBA and NDEA by 202, 150,
      110, 95, 94, 77 and 37%, respectively.

PMID- 9625857
TI  - Concomitant treatment with mild hyperthermia, cisplatin and low dose-rate
      irradiation in human ovarian cancer cells sensitive and resistant to cisplatin.
AB  - Hyperthermia has been shown to be an effective radiation sensitizer. Cisplatin
      has also been shown to cause radiosensitization. In part, the sensitization is
      through the inhibition of repair of radiation damage. In this study we have set
      out to combine low dose-rate irradiation (during which extensive repair occurs)
      with both cisplatin and hyperthermia to maximize the radiation sensitizing
      effect. Two human ovarian carcinoma cell lines, one parental (A2780S) and the
      other a cisplatin resistant derivative (A2780CP) cell line were used in these
      experiments. Long duration hyperthermia at 40 degrees C was combined with low
      concentrations of cisplatin (0.5-3 microg/ml) and low dose-rate irradiation
      (LDRI). The responses to the individual treatments showed that there was cross
      resistance in the two cell lines for cisplatin and radiation, but for
      hyperthermia the opposite effect was found. When all treatments were given
      concurrently the response was greater than the calculated response of all three
      individual treatments, indicating a synergistic interaction. The effect was
      greater in the cisplatin resistant cell line. The combination of mild
      hyperthermia, low dose cisplatin and LDRI are a good combination for potential
      clinical application. In addition, this could be a good approach to deal with
      cisplatin resistance.

PMID- 9625858
TI  - nm23 protein expression in renal cell tumors: the role of the cell type.
AB  - This study investigated nm23 protein expression in renal cell carcinomas to
      determine the relationship between nm23 protein expression and grade, stage,
      prognosis and the cell type. 89 cases were examined by immunohistochemistry.
      Tubular epithelia were homogeneously stained. Cytoplasmic nm23 protein levels
      were reduced in renal cell carcinoma. nm23 protein levels persisted in
      oncocytomas, which are accepted to be benign. Cytoplasmic nm23 staining intensity
      did not show any correlation with stage and grade of tumor nor prognosis.
      Reduction in nm23 protein levels may have a role during renal cell carcinoma
      pathogenesis but not in progression or metastasis suppression.

PMID- 9625859
TI  - Vascular invasion in high grade sarcoma of the extremity is associated with short
      overall survival.
AB  - Intravascular sarcoma thrombi were histologically evident in 2% of 470 patients
      with soft tissue or bone sarcoma treated during the last 3 years. Vascular
      invasion by sarcoma in our series was associated with an aggressive disease and
      short-term overall survival. In all the cases there was a large or locally
      advanced primary high grade sarcoma, and in all but one case, where preoperative
      chemotherapy was administered, the response was far from satisfactory. The post
      operative course in 70% of the patients was characterized by early systemic
      spread, and a median overall survival of 9.5 months. The gloomy prognosis of our
      patients does not necessarily stem only from the presence of vascular invasion,
      but may also be related to other factors as histologic grade and tumor size.
      However, as compared to similar cases in our patient population, which did not
      show vascular invasion, the course here was more violent and short.

PMID- 9625860
TI  - Evidence for selective use of bone scans in early stage breast cancer.
AB  - To determine the usefulness of bone scans in detecting metastatic disease in
      women with early stage breast cancer, records of 193 patients who had bone scans
      preformed and underwent breast conservation therapy at a single institution were
      reviewed. Patients with invasive T1 or T2 breast carcinomas were eligible for
      this study; patients with a true positive bone scan were excluded from
      conservation therapy and, thus, were excluded from this study. The incidence of
      false positive bone scans in this study population was 32.6% (63/193 patients).
      Patients over 50 years of age had a significantly greater incidence of false
      positive bone scans (p<0. 05). In the 63 patients with false positive bone scans,
      101 radiographs were performed to exclude metastatic disease in areas of
      increased uptake identified on bone scan. No significant difference in the rate
      of false positive bone scans was seen in relation to tumor size, pathologic or
      clinical nodal status or hormone receptor activity of the primary tumor. Thus,
      selective use of bone scans is advocated in patients with early stage (T1 or T2)
      breast cancer.

PMID- 9625861
TI  - Electrophoresis of BRCA1 oncosuppressor.
AB  - BRCA1 is a familial breast and ovarian cancer susceptibility gene and encodes
      proteins that function as tumor suppressors in human breast cancer cells. To
      elucidate the biological function of BRCA1, knowledge of cellular localization is
      needed. This can be achieved by using specific antibodies, so in a first step, we
      characterized by Western blot analysis the rabbit polyclonal antibodies (K-18)
      and (D-20) raised against the amino-terminus of human BRCA1 protein, and the
      polyclonal antibodies (C-20) and (I-20) raised against the carboxy terminus of
      human BRCA1 protein. The 220-kDa band corresponding to BRCA1 protein was
      recognized by the four tested antibodies in two mammary carcinoma cell lines
      (HBL100 and MCF7).

PMID- 9625862
TI  - Single-channel activations and concentration jumps: comparison of recombinant
      NR1a/NR2A and NR1a/NR2D NMDA receptors.
AB  - 1. We have expressed recombinant NR1a/NR2A and NR1a/NR2D N-methyl-D-aspartate
      (NMDA) receptor channels in Xenopus oocytes and made recordings of single-channel
      and macroscopic currents in outside-out membrane patches. For each receptor type
      we measured (a) the individual single-channel activations evoked by low glutamate
      concentrations in steady-state recordings, and (b) the macroscopic responses
      elicited by brief concentration jumps with high agonist concentrations, and we
      explore the relationship between these two sorts of observation. 2. Low
      concentration (5-100 nM) steady-state recordings of NR1a/NR2A and NR1a/NR2D
      single-channel activity generated shut-time distributions that were best fitted
      with a mixture of five and six exponential components, respectively. Individual
      activations of either receptor type were resolved as bursts of openings, which we
      refer to as 'super-clusters'. 3. During a single activation, NR1a/NR2A receptors
      were open for 36 % of the time, but NR1a/NR2D receptors were open for only 4 % of
      the time. For both, distributions of super-cluster durations were best fitted
      with a mixture of six exponential components. Their overall mean durations were
      35.8 and 1602 ms, respectively. 4. Steady-state super-clusters were aligned on
      their first openings and averaged. The average was well fitted by a sum of
      exponentials with time constants taken from fits to super-cluster length
      distributions. It is shown that this is what would be expected for a channel that
      shows simple Markovian behaviour. 5. The current through NR1a/NR2A channels
      following a concentration jump from zero to 1 mM glutamate for 1 ms was well
      fitted by three exponential components with time constants of 13 ms (rising
      phase), 70 ms and 350 ms (decaying phase). Similar concentration jumps on
      NR1a/NR2D channels were well fitted by two exponentials with means of 45 ms
      (rising phase) and 4408 ms (decaying phase) components. During prolonged exposure
      to glutamate, NR1a/NR2A channels desensitized with a time constant of 649 ms,
      while NR1a/NR2D channels exhibited no apparent desensitization. 6. We show that
      under certain conditions, the time constants for the macroscopic jump response
      should be the same as those for the distribution of super-cluster lengths, though
      the resolution of the latter is so much greater that it cannot be expected that
      all the components will be resolvable in a macroscopic current. Good agreement
      was found for jumps on NR1a/NR2D receptors, and for some jump experiments on
      NR1a/NR2A. However, the latter were rather variable and some were slower than
      predicted. Slow decays were associated with patches that had large currents.

PMID- 9625863
TI  - Modulation of ATP-gated non-selective cation channel (P2X1 receptor) activation
      and desensitization by the actin cytoskeleton.
AB  - 1. ATP-gated non-selective cation channels from the rat vas deferens (P2X1
      receptors) were stably expressed in HEK 293 cells, assayed by patch clamp on the
      first day after passage of the culture, and found to have whole-cell current
      kinetics markedly faster in both activation and desensitization than those found
      in the native vas deferens tissue, in agreement with previous reports. 2. By the
      second day after passage of the culture, however, the whole-cell current kinetics
      of the expressed receptors shifted, slowing in both activation and
      desensitization. The kinetic change correlated with a change in phenotype of the
      host cells from round to flat, and the slower kinetics were similar to native
      P2X1 currents recorded from dissociated rat vas deferens smooth muscle cells. Two
      point mutations in a pore-like domain near or within the second transmembrane
      domain of the P2X1 receptor appeared to confer on the receptor the inability to
      effect this change in kinetics over time. 3. Treatment of cells on day 3 after
      passage with cytochalasins B or D caused a reversion to the rapid kinetics
      phenotype, implicating the actin cytoskeleton in the development of the native
      kinetics. P2X1 receptors may therefore require interaction with an intact actin
      cytoskeleton for native kinetics, and the mutants may be defective either in
      interaction with the actin skeleton or in coupling the interaction to gating.

PMID- 9625864
TI  - Calcium permeability and block at homomeric and heteromeric P2X2 and P2X3
      receptors, and P2X receptors in rat nodose neurones.
AB  - 1. Whole-cell recordings were made from HEK 293 (human embryonic kidney) cells
      stably transfected with cDNAs encoding P2X2, P2X3 or both receptors (P2X2/3) and
      from cultured rat nodose neurones. Nodose neurones all showed immunoreactivity
      for both P2X2 and P2X3, but not P2X1, receptors. 2. Reversal potentials were
      measured in extracellular sodium, N-methyl-D-glucamine (NMDG) and NMDG containing
      5 mM Ca2+; the values were used to compute relative permeabilities (PNMDG/PNa and
      PCa/PNa). PNMDG/PNa was not different for P2X2, P2X2/3 and nodose neurones (0.03)
      but was significantly higher (0.07) for P2X3 receptors. PCa/PNa was not different
      among P2X3, P2X2/3 and nodose neurones (1.2-1.5) but was significantly higher
      (2.5) for P2X2 receptors. 3. External Ca2+ inhibited purinoceptor currents with
      half-maximal concentrations of 5 mM at the P2X2 receptor, 89 mM at the P2X3
      receptor and 15 mM at both the P2X2/3 heteromeric receptor and nodose neurones.
      In each case, the inhibition was voltage independent and was overcome by
      increasing concentrations of agonist. 4. These results may indicate that Ca2+
      permeability of the heteromeric (P2X2/3) channel is dominated by that of the P2X3
      subunit, while Ca2+ block of the receptor involves both P2X2 and P2X3 subunits.
      The correspondence in properties between P2X2/3 receptors and nodose ganglion
      neurones further supports the conclusion that the native alpha,beta-methylene ATP
      sensitive receptor is a P2X2/3 heteromultimer.

PMID- 9625865
TI  - Voltage-dependent inactivation of the human K+ channel KvLQT1 is eliminated by
      association with minimal K+ channel (minK) subunits.
AB  - 1. The time course and voltage dependence of inactivation of KvLQT1 channels
      expressed in Xenopus oocytes were studied using two-microelectrode voltage-clamp
      techniques. 2. Tail current analysis was used to characterize the kinetics of
      channel inactivation and deactivation. The time constant for recovery from
      channel inactivation was voltage dependent and varied from 30 +/- 2 ms at -90 mV
      to 36 +/- 1 ms at -30 mV. The time constant for deactivation varied from 186 +/-
      21 to 986 +/- 43 ms over the same voltage range. 3. Inactivation of KvLQT1
      channels was incomplete, reducing fully activated current by 35 % at +40 mV.
      Inactivation of KvLQT1 channels was half-maximal at -18 +/- 2 mV. 4. The onset of
      KvLQT1 channel inactivation during a single depolarization to +20 mV was
      exponential (tau = 130 +/- 10 ms), and developed after a delay of approximately
      75 ms. In contrast, when inactivation was reinduced following transient recovery
      of channels to the open state(s), the onset of inactivation was immediate and 10
      times faster. These findings suggest multiple open states, and a sequential
      gating model for KvLQT1 channel activation and inactivation (C1<==> Cn<==> O1<==>
      O2<==>I). 5. Delayed rectifier K+ (IKs) channels formed by heteromultimeric
      coassembly of KvLQT1 and minimal K+ channel (minK) subunits did not inactivate.
      Thus, minK subunits eliminate, or greatly slow, the gating associated with
      channel inactivation when coassembled with KvLQT1.

PMID- 9625866
TI  - Role of tyrosine phosphorylation in leptin activation of ATP-sensitive K+
      channels in the rat insulinoma cell line CRI-G1.
AB  - 1. Using whole-cell and cell-attached recording configurations, the role of
      phosphorylation in leptin activation of ATP-sensitive K+ (KATP) channels was
      examined in the rat CRI-G1 insulinoma cell line. 2. Whole-cell current clamp
      recordings demonstrated that, following dialysis with the non-hydrolysable ATP
      analogue 5'-adenylylimidodiphosphate (AMP-PNP; 3-5 mM), the leptin-induced
      hyperpolarization and increase in K+ conductance were completely inhibited. 3.
      Under current clamp conditions, application of the broad-spectrum protein kinase
      inhibitor H-7 (10 microM) had no effect on the resting membrane potential or
      slope conductance of CRI-G1 insulinoma cells and did not occlude the actions of
      leptin. 4. Application of the tyrosine kinase inhibitors genistein (10 microM),
      tyrphostin B42 (10 microM) and herbimycin A (500 nM) all resulted in activation
      of KATP channels. In cell-attached recordings, the presence of tyrphostin B42 (10
      microM) in the pipette solution activated tolbutamide-sensitive KATP channels in
      CRI-G1 cells. In contrast, the inactive analogues of genistein and tyrphostin B42
      were without effect. 5. The serine/threonine-specific protein phosphatase
      inhibitors okadaic acid (50 nM) and cyclosporin A (1 microM) did not prevent or
      reverse leptin activation of KATP channels. In contrast, whole-cell dialysis with
      the tyrosine phosphatase inhibitor orthovanadate (500 microM) prevented the
      actions of both leptin and tyrphostin B42. 6. In conclusion, leptin activation of
      KATP channels appears to require inhibition of tyrosine kinases and subsequent
      dephosphorylation. This process is likely to occur prior to activation of
      phosphoinositide 3-kinase (PI 3-kinase) as wortmannin prevented activation of
      KATP channels by tyrphostin B42.

PMID- 9625867
TI  - The erg inwardly rectifying K+ current and its modulation by thyrotrophin
      releasing hormone in giant clonal rat anterior pituitary cells.
AB  - 1. The voltage-dependent inwardly rectifying K+ current (IK,IR) of clonal rat
      anterior pituitary cells (GH3/B6) was investigated in solutions with
      physiological K+ gradient using giant polynuclear cells. 2. IK,IR was isolated by
      the use of the selective erg (ether-a-go-go-related gene) channel blocker E-4031.
      In external 5 mM K+ solution, IK,IR carried steady-state outward current in the
      potential range between -60 and 0 mV, with a maximum current amplitude at -40 mV.
      Negative to the K+ equilibrium potential, EK, large transient inward currents
      occurred. 3. A selective pharmacological block of IK,IR induced a sustained
      depolarization of the membrane potential when Ca2+ action potentials were
      blocked, confirming the contribution of IK,IR to the resting membrane potential
      of GH3/B6 cells. 4. Thyrotrophin-releasing hormone (TRH) reduced effectively the
      sustained outward and the transient inward IK,IR. The magnitude of a TRH-induced
      depolarization of the membrane potential was consistent with an almost complete
      reduction of IK,IR. 5. The results demonstrate that the TRH-induced reduction of
      IK,IR is able to mediate the resting potential depolarization, suggesting that
      the increase in the frequency of action potentials occurring during the second
      phase of the TRH response in GH cells should be sustained by IK,IR inhibition.
      Moreover, this is the first evidence of a ligand-induced physiological modulation
      of an erg-mediated current.

PMID- 9625868
TI  - Ca2+-inhibited non-inactivating K+ channels in cultured rat hippocampal pyramidal
      neurones.
AB  - 1. Whole-cell perforated-patch recording from cultured CA1-CA3 pyramidal neurones
      from neonatal rat hippocampus (20-22 C; [K+]o = 2.5 mM) revealed two previously
      recorded non-inactivating (sustained) K+ outward currents: a voltage-independent
      'leak' current (Ileak) operating at all negative potentials, and, at potentials
      >= -60 mV, a time- and voltage-dependent 'M-current' (IK(M)). Both were inhibited
      by 1 mM Ba2+ or 10 microM oxotremorine-M (Oxo-M). In ruptured-patch recording
      using Ca2+-free pipette solution, Ileak was strongly enhanced, and was inhibited
      by 1 mM Ba2+ but unaffected by 0.5 mM 4-aminopyridine (4-AP), 1 mM
      tetraethylammonium (TEA) or 1-10 nM margatoxin. 2. Single channels underlying
      these currents were sought in cell-attached patch recordings. A single class of
      channels of conductance approximately 7 pS showing sustained activity at resting
      potential and above was identified. These normally had a very low open
      probability (Po < 0. 1), which, however, showed a dramatic and reversible
      increase (to about 0.9 at approximately 0 mV) following the removal of Ca2+ from
      the bath. Under these (Ca2+-free) conditions, single-channel Po showed both
      voltage-dependent and voltage-independent components on patch depolarization from
      resting potential. The mean activation curve was fitted by a modified Boltzmann
      equation. When tested, all channels were reversibly inhibited by addition of 10
      microM Oxo-M to the bath solution. 3. The channels maintained their high Po in
      patches excised in inside-out mode into a Ca2+-free internal solution and were
      strongly inhibited by application of Ca2+ to the inner face of the membrane (IC50
      = 122 nM); this inhibition was observed in the absence of MgATP, and therefore
      was direct and unrelated to channel phosphorylation/dephosphorylation. 4.
      Channels in patches excised in outside-out mode were blocked by 1 mM Ba2+ but
      were unaffected by 4-AP or TEA. 5. Channels in cell-attached patches were
      inhibited after single spikes, yielding inward ensemble currents lasting several
      hundred milliseconds. This was prevented in Ca2+-free solution, implying that it
      was due to Ca2+ entry. 6. The properties of these channels (block by internal
      Ca2+ and external Oxo-M and Ba2+, and the presence of both voltage-dependent and
      voltage-independent components in their Po/V relationship) show points of
      resemblance to those expected for channels associated with both Ileak and IK(M)
      components of the sustained macroscopic currents. For this reason we designate
      them Ksust ('sustained current') channels. Inhibition of these channels by Ca2+
      entry during an action potential may account for some forms of Ca2+-dependent
      after-depolarization. Their high sensitivity to internal Ca2+ may provide a new,
      positive feedback mechanism for cell excitation operating at low (near-resting)
      [Ca2+]i.

PMID- 9625869
TI  - K+ channel block-induced mammalian neuroblastoma cell swelling: a possible
      mechanism to influence proliferation.
AB  - 1. A variety of studies have suggested that K+ channel activity is a key
      determinant for cell progression through the G1 phase of mitosis. We have
      previously proposed that K+ channels control the activity of cell cycle
      regulating proteins via regulation of cell volume. In order to test this
      hypothesis, we measured, with a Coulter counter and under different experimental
      conditions, the volume and rate of proliferation of neuroblastoma x glioma hybrid
      NG108-15 cells. 2. The K+ channel blockers TEA (1-10 mM), 4-aminopyridine (0.2-2
      mM) and Cs+ (2.5-10 mM) increased the cell volume and decreased the rate of cell
      proliferation. Proliferation was fully inhibited when cell volume was increased
      by 25 %. 3. A 40 % increase in the culture medium osmolarity with NaCl induced a
      25 % increase in cell volume and an 82 % decrease in the rate of cell
      proliferation. A 40 % increase in the culture medium osmolarity with mannitol
      induced a 9 % increase in cell volume and a 60 % decrease in the rate of cell
      proliferation. 4. The Cl- channel blocker NPPB (5-nitro-2-(3-phenylpropylamino)
      benzoic acid; 50 microM) induced a 12 % increase in cell volume and a 77 %
      decrease in the rate of cell proliferation. 5. A 24 % reduction in the culture
      medium osmolarity with H2O induced a 21 % decrease in cell volume and a 32 %
      increase in the rate of cell proliferation. 6. Under whole-cell patch-clamp
      conditions, antibiotics (penicillin plus streptomycin) decreased the voltage
      dependent K+ current. Omission of antibiotics from the culture medium induced a
      10 % decrease in the cell volume and a 32 % increase in the rate of cell
      proliferation. 7. These results suggest that the mechanisms controlling cell
      proliferation are strongly influenced by the factors which determine cell volume.
      This could take into account the role in mitogenesis of K+ channels and of other
      ionic pathways involved in cell volume regulation.

PMID- 9625870
TI  - Differential inhibition of N and P/Q Ca2+ currents by 5-HT1A and 5-HT1D receptors
      in spinal neurons of Xenopus larvae.
AB  - 1. In whole-cell patch clamp recordings made from non-sensory neurons acutely
      isolated from the spinal cord of Xenopus (stage 40-42) larvae, two forms of
      inhibition of the high voltage-activated (HVA) Ca2+ currents were produced by 5
      HT. One was voltage dependent and associated with both slowing of the activation
      kinetics and shifting of the voltage dependence of the HVA currents. This
      inhibition was relieved by strong depolarizing prepulses. A second form of
      inhibition was neither associated with slowing of the activation kinetics nor
      relieved by depolarizing prepulses and was thus voltage independent. 2. In all
      neurons examined, 5-HT (1 microM) reversibly reduced 34 +/- 1.6 % (n = 102) of
      the HVA Ca2+ currents. In about 40 % of neurons, the inhibition was totally
      voltage independent. In another 5 %, the inhibition was totally voltage
      dependent. In the remaining neurons, inhibition was only partially (by around 40
      %) relieved by a large depolarizing prepulse, suggesting that in these, the
      inhibition consisted of both voltage-dependent and -independent components. 3. By
      using selective channel blockers, we found that 5-HT acted on both N- and P/Q
      type channels. However, whereas the inhibition of P/Q-type currents was only
      voltage independent, the inhibition of N-type currents had both voltage-dependent
      and -independent components. 4. The effects of 5-HT on HVA Ca2+ currents were
      mediated by 5-HT1A and 5-HT1D receptors. The 5-HT1A receptors not only
      preferentially caused voltage-independent inhibition, but did so by acting mainly
      on the omega-agatoxin-IVA-sensitive Ca2+ channels. In contrast, the 5-HT1D
      receptor produced both voltage-dependent and -independent inhibition and was
      preferentially coupled to omega-conotoxin-GVIA sensitive channels. This
      complexity of modulation may allow fine tuning of transmitter release and calcium
      signalling in the spinal circuitry of Xenopus larvae.

PMID- 9625871
TI  - Presynaptic inhibition by 5-HT1B receptors of glutamatergic synaptic inputs onto
      serotonergic caudal raphe neurones in rat.
AB  - 1. Autonomous, pacemaker-like activity of serotonergic raphe neurones and its
      autoregulation by somatodendritic 5-HT1A receptors are well described, but little
      is known of synaptic inputs onto raphe neurones or their modulation. Therefore,
      we recorded unitary excitatory postsynaptic currents (EPSCs) in caudal raphe
      neurones (raphe obscurus and pallidus) following local electrical stimulation in
      a neonatal rat brainstem slice preparation; most neurones (79 %; n = 72/91)
      recovered following post hoc immunohistochemistry were tryptophan hydroxylase
      immunoreactive, indicating that they were serotonergic. 2. Evoked EPSCs occurred
      at relatively constant latency with variable amplitude and apparent 'failures' at
      fixed suprathreshold stimulus intensity. At -60 mV, EPSCs were wholly due to CNQX
      sensitive, non-NMDA glutamate receptors; at depolarized potentials, a small AP-5
      sensitive NMDA component was often observed. 3. EPSCs were potently and
      reversibly inhibited by 5-HT with an EC50 of 0.1 microM. This effect was mimicked
      by 5-HT1B agonists (CP-93,129 and anpirtoline), but not by a 5-HT1A agonist (8-OH
      DPAT), indicating that 5-HT1B receptors mediate the inhibition of EPSCs. 4.
      Multiple lines of evidence indicate that inhibition of EPSCs by 5-HT was mediated
      presynaptically. First, currents evoked by exogenous glutamate application were
      unaffected by 5-HT and/or 5-HT1B agonists. In addition, the frequency of
      spontaneous glutamatergic miniature EPSCs was diminished by CP-93,129 and paired
      pulse facilitation of EPSCs was enhanced by 5-HT. Finally, the 5-HT1B receptor
      agonists that blocked synaptic transmission had no effect on resting membrane
      properties of raphe neurones. 5. These data indicate that serotonergic caudal
      raphe neurones receive glutamatergic inputs that are inhibited by presynaptic 5
      HT1B receptors; inhibition of excitatory synapses onto raphe cells may represent
      a novel mechanism for autoregulation of serotonergic neuronal activity by 5-HT.

PMID- 9625872
TI  - Control of pulsatile 5-HT/insulin secretion from single mouse pancreatic islets
      by intracellular calcium dynamics.
AB  - 1. Glucose-induced insulin release from single islets of Langerhans is pulsatile.
      We have investigated the correlation between changes in cytosolic free calcium
      concentration ([Ca2+]i) and oscillatory insulin secretion from single mouse
      islets, in particular examining the basis for differences in secretory responses
      to intermediate and high glucose concentrations. Insulin release was monitored in
      real time through the amperometric detection of the surrogate insulin marker 5
      hydroxytryptamine (5-HT) via carbon fibre microelectrodes. The [Ca2+]i was
      simultaneously recorded by whole-islet fura-2 microfluorometry. 2. In 82 % of the
      experiments, exposure to 11 mM glucose evoked regular high-frequency (average,
      3.4 min-1) synchronous oscillations in amperometric current and [Ca2+]i. In the
      remaining experiments (18 %), 11 mM glucose induced an oscillatory pattern
      consisting of high-frequency [Ca2+]i oscillations that were superimposed on low
      frequency (average, 0.32 min-1) [Ca2+]i waves. Intermittent high-frequency
      [Ca2+]i oscillations gave rise to a similar pattern of pulsatile 5-HT release. 3.
      Raising the glucose concentration from 11 to 20 mM increased the duration of the
      steady-state [Ca2+]i oscillations without increasing their amplitude. In
      contrast, both the duration and amplitude of the associated 5-HT transients were
      increased by glucose stimulation. The amount of 5-HT released per secretion cycle
      was linearly related to the duration of the underlying [Ca2+]i oscillations in
      both 11 and 20 mM glucose. The slopes of the straight lines were identical,
      indicating that there is no significant difference between the ability of calcium
      oscillations to elicit 5-HT/insulin release in 11 and 20 mM glucose. 4. In situ 5
      HT microamperometry has the potential to resolve the high-frequency oscillatory
      component of the second phase of glucose-induced insulin secretion. This
      component appears to reflect primarily the duration of the underlying [Ca2+]i
      oscillations, suggesting that glucose metabolism and/or access to glucose
      metabolites is not rate limiting to fast pulsatile insulin release.

PMID- 9625873
TI  - The role of Ca2+ in volume regulation induced by Na+-coupled alanine uptake in
      single proximal tubule cells isolated from frog kidney.
AB  - 1. It has been suggested that epithelial cells maintain cell volume and function,
      in the face of changes in the rate of transepithelial transport, by activation of
      volume-regulatory pathways. 2. The aim of the following study was to examine
      directly the effect of an alteration in Na+-coupled alanine transport on cell
      length in single proximal tubule cells isolated from frog kidney. 3. An optical
      technique was used to examine the change in cell length induced by 5 mM L
      alanine. 4. On addition of L-alanine to the bath there was an initial increase in
      cell length to a peak value. This was followed by two types of response. In
      eighteen out of thirty-one cells a typical volume-regulatory response was
      observed. The remaining cells showed no volume regulation. 5. Volume regulation
      was not affected by the removal of extracellular Ca2+. The mean degrees of
      recovery were 159 +/- 21 % (n = 18) and 144 +/- 18 % (n = 8) in the presence and
      absence of Ca2+, respectively. 6. Volume regulation was inhibited by depletion of
      intracellular Ca2+ stores, or in the presence of either Gd3+ or DIDS. The mean
      degrees of regulation were 55.4 +/- 9.2 % (n = 7), 68.2 +/- 18.8 % (n = 7) and
      69.1 +/- 14.3 % (n = 7), respectively. 7. The alanine-induced increases in cell
      length were both stereospecific and Na+ dependent. 8. The evidence suggests that
      volume regulation induced by Na+-coupled alanine uptake may be dependent on the
      release of Ca2+ from intracellular stores. This is in contrast to volume
      regulation induced by hypotonic shock, which appears to require extracellular
      Ca2+. Results obtained using a hypotonic shock should, therefore, be viewed with
      caution.

PMID- 9625874
TI  - Detection and functional characterization of ryanodine receptors from sea urchin
      eggs.
AB  - 1. Immunoblot analysis, [3H]ryanodine binding, and planar lipid bilayer
      techniques were used to identify and characterize the functional properties of
      ryanodine receptors (RyRs) from Lytechinus pictus and Strongylocentrotus
      purpuratus sea urchin eggs. 2. An antibody against mammalian skeletal RyRs
      identified an approximately 400 kDa band in the cortical microsomes of sea urchin
      eggs while a cardiac-specific RyR antibody failed to recognize this protein.
      [3H]Ryanodine binding to cortical microsomes revealed the presence of a high
      affinity (Kd = 13 nM), saturable (maximal density of receptor sites, Bmax = 1.56
      pmol (mg protein)-1) binding site that exhibited a biphasic response to Ca2+. 3.
      Upon reconstitution of cortical microsomes into lipid bilayers, only sparse and
      unstable openings of a high-conductance cation channel were detected. Addition of
      crude sea urchin egg homogenate to the cytosolic (cis side) of the channel
      increased the frequency of openings and stabilized channel activity. The
      homogenate-activated channels were Ca2+ sensitive, selective for Ca2+ over Cs+,
      and driven by ryanodine into a long-lived subconductance state that represented
      approximately 40 % of the full conductance level. Homogenate dialysed in
      membranes with a molecular weight cut-off <= 2000 lacked the capacity to increase
      the frequency of RyR openings and to stabilize channel activity. 4. Direct
      application of cyclic adenosine diphosphoribose (cADPR) or photolysis of NPE
      cADPR ('caged' cADPR) by ultraviolet laser pulses produced transient activation
      of sea urchin egg RyRs. Calmodulin (CaM) failed to activate reconstituted RyRs;
      however, channel activity was inhibited by the CaM blocker trifluoroperazine,
      suggesting that CaM was necessary but not sufficient to sustain RyR activity. 5.
      These findings suggest that a functional Ca2+ release unit in sea urchin eggs is
      a complex of several molecules, one of which corresponds to a protein
      functionally similar to mammalian RyRs.

PMID- 9625875
TI  - Caesium blocks depolarizing after-potentials and phasic firing in rat supraoptic
      neurones.
AB  - 1. The effects of Cs+ on the action potential, post-train after-hyperpolarization
      (AHP), Ca2+-dependent post-spike depolarizing after-potential (DAP) and phasic
      firing were examined during intracellular recordings from magnocellular
      neurosecretory cells (MNCs) in superfused rat hypothalamic explants. 2.
      Extracellular Cs+ reversibly inhibited (IC50, approximately 1 mM) DAPs, and
      associated after-discharges, that followed brief spike trains in each of sixteen
      cells tested. Although bath application of Cs+ also provoked a small reversible
      depolarization, inhibition of the DAP was retained when membrane voltage was kept
      constant by current injection. 3. Application of Cs+ had no significant effects
      on spike duration (n = 8), frequency-dependent spike broadening (n = 8), spike
      hyperpolarizing after-potentials (n = 14), or the amplitude of the isolated AHP
      (n = 7). Caesium-evoked inhibition of the DAP, therefore, does not result from
      diminished spike-evoked Ca2+ influx, and may reflect direct blockade of the
      conductance underlying the DAP. 4. Inhibition of the DAP was associated with an
      enhancement of the amplitude and duration of the AHP, indicating that the
      currents underlying the AHP and the DAP overlap in time following a train of
      action potentials, and that the relative magnitude of these currents is an
      important factor in determining the shape and time course of post-train after
      potentials. 5. Bath application of Cs+ reversibly abolished phasic firing in each
      of seven cells tested. This effect was reversible and persisted at all
      subthreshold voltages tested. These results indicate that the current underlying
      the DAP is necessary for the genesis of plateau potentials and phasic firing in
      MNCs.

PMID- 9625876
TI  - Mathematical model of vertebrate gap junctions derived from electrical
      measurements on homotypic and heterotypic channels.
AB  - 1. A mathematical model has been developed which describes the conductive and
      kinetic properties of homotypic and heterotypic gap junction channels of
      vertebrates. 2. The model consists of two submodels connected in series. Each
      submodel simulates a hemichannel and consists of two conductances corresponding
      to a high (H) and low (L) conductance state and a switch, which simulates the
      voltage-dependent channel gating. 3. It has been assumed that the conductances of
      the high state and low state vary exponentially with the voltage across the
      hemichannel. 4. The parameters of the exponentials can be derived from data of
      heterotypic or homotypic channels. As a result, the behaviour of heterotypic
      channels can be predicted from homotypic channel data and vice versa. 5. The two
      switches of a channel are governed by the voltage drop across the respective
      hemichannel. The switches of a channel work independently, thus giving rise to
      four conformational states, i.e. HH, LH, HL and LL. 6. The computations show that
      the dogma of a constant conductance for homotypic channels results from the
      limited physiological range of transjunctional voltages (Vj) and the kinetic
      properties of the channel, so a new fitting procedure is presented. 7. Simulation
      of the kinetic properties at the multichannel level revealed current time courses
      which are consistent with a contingent gating. 8. The calculations have also
      shown that the channel state LL is rare and of short duration, and hence easy to
      miss experimentally. 9. The design of the model has been kept flexible. It can be
      easily expanded to include additional features, such as channel substates or a
      closed state.

PMID- 9625877
TI  - Properties of gamma-frequency oscillations initiated by propagating population
      bursts in retrohippocampal regions of rat brain slices.
AB  - 1. In the hippocampal formation in vivo, brief periods of gamma-frequency
      activity follow population bursts called sharp waves. The approximately 200 Hz
      activity of the sharp wave itself may serve to enhance synaptic connections and
      the approximately 40 Hz gamma activity has been offered as a mechanism for
      solving the 'binding' problem. We describe epochs of gamma-frequency activity
      which follow population spikes evoked by low frequency repetitive extracellular
      stimuli in retrohippocampal neurons of horizontal rat brain slices. 2. gamma
      Frequency activity recorded intracellularly from deep layer neurons of entorhinal
      cortex, presubiculum and parasubiculum consisted of one action potential
      correlated with each of the three to five gamma cycles recorded with a proximate
      field potential electrode. A minority of cells exhibited only sub-threshold gamma
      frequency membrane potential oscillations (ranging from 5 to 10 mV). No cells
      fired more than one spike per gamma cycle under any conditions. 3. The range of
      synchrony varied from individual cells which showed gamma-frequency firing
      without corresponding oscillations in close field recordings to field potential
      recordings of oscillations which were well correlated across regions. The lead or
      lag between any two retrohippocampal regions was in the direction of the
      conduction delay for the primary population spike, but typically was less, and
      approached zero milliseconds for some cycles in most cells. The level of
      synchrony was stable for particular stimulating conditions (intensity,
      stimulation rate, stimulus location). 4. The duration of the period of gamma
      activity had the duration of a slow depolarizing potential which was mediated by
      NMDA receptor activation. NMDA receptor antagonists or low concentrations of AMPA
      receptor antagonists reduced the duration of, or completely abolished the slow
      potential, thereby eliminating the gamma portion of the evoked response. 5. gamma
      Frequency firing was eliminated by the GABAA receptor antagonist picrotoxin but
      small (< 5 mV) membrane potential oscillations remained after focal picrotoxin
      applications, and these exhibited the voltage dependence of EPSPs. Bath
      application of thiopental lowered the frequency of gamma oscillations, confirming
      the involvement of GABAA receptors. 6. The GABAB receptor antagonist 2-hydroxy
      saclofen appeared to enhance the gamma activity by increasing the duration of the
      gamma epoch and increasing the amplitude of individual gamma cycles in field
      potential recordings. These saclofen-induced cycles were, however, less well
      synchronized across regions. 7. We show that synchronous gamma (40-100 Hz)
      activity follows population bursts by deep layer retrohippocampal neurons in
      undrugged slices from rat brain. Responses from medial entorhinal, parasubicular
      or presubicular cells were not distinguishable. These events can be initiated by
      a propagating population spike. We suggest that an NMDA receptor mediated
      depolarization enables the network of deep layer retrohippocampal neurons to
      oscillate by providing a sustained excitation, the duration of which determines
      the duration of the gamma episode. gamma-Frequency firing is primarily the result
      of GABAA receptor dependent inhibition during this period of sustained
      depolarization. Recurrent excitation appears to be inconsequential for principal
      cell firing, but may contribute to interneuron firing.

PMID- 9625878
TI  - Neuroeffector transmission in arterioles of the guinea-pig choroid.
AB  - 1. Using conventional microelectrode techniques, membrane potentials were
      recorded from smooth muscle cells of guinea-pig choroidal arterioles. 2.
      Transmural stimulation initiated excitatory junction potentials (EJPs) which were
      abolished by either guanethidine or alpha,beta-methylene-ATP but not by
      phentolamine, indicating that they resulted from activation of purinoceptors. 3.
      Trains of stimuli evoked EJPs which were followed by a slow depolarization, an
      inhibitory junction potential (IJP) or a biphasic membrane potential change which
      consisted of an IJP and a subsequent slow depolarization. 4. Slow depolarizations
      were abolished by either phentolamine or guanethidine, indicating that they
      resulted from activation of alpha-adrenoceptors. 5. IJPs were abolished by
      atropine but not by guanethidine, and were reduced by 50 % by apamin with the
      residual response being abolished by charybdotoxin, indicating that they resulted
      from the activation of muscarinic receptors which open two sets of Ca2+-activated
      K+ channels. 6. Most responses were followed by slow hyperpolarizations. These
      were almost abolished by L-nitroarginine, an effect which was partly overcome by
      L-arginine, and were abolished by glibenclamide, indicating that they resulted
      from the release of NO and activation of ATP-sensitive K+ channels. 7.
      Immunohistochemical analysis showed that arterioles were densely innervated by
      adrenergic nerve fibres. A population of fibres, likely to be cholinergic, was
      also identified. Furthermore, populations of nerve fibres immunoreactive to
      antibodies against either nitric oxide synthase (NOS) or substance P (SP) were
      also identified. 8. These findings indicate that choroidal arterioles of the
      guinea-pig are innervated by at least three different populations of nerves,
      adrenergic nerves which evoke excitatory responses, cholinergic nerves which
      evoke inhibitory responses and a population of nerves which cause the release of
      NO.

PMID- 9625879
TI  - Effects of membrane potential on the voltage dependence of motility-related
      charge in outer hair cells of the guinea-pig.
AB  - 1. Isolated outer hair cells (OHCs) from the guinea-pig were whole-cell voltage
      clamped to study the influence of initial voltage on the voltage dependence of
      motility-related gating current or, equivalently, on the voltage dependence of
      membrane capacitance. 2. Prepulse delivery caused changes in the magnitude of
      motility-related gating currents, which are due predominantly to shifts in the
      voltage at peak capacitance (VpkCmm). Depolarization shifts VpkCm in the
      hyperpolarizing direction, and hyperpolarization does the opposite. The mean
      shift between -120 and +40 mV prepulse states with long-term holding potentials
      (> 2 min) at -80 mV was 14. 67 +/- 0.95 mV (n = 10; mean +/- s.e.m.). 3. The
      effect of initial membrane potential is sigmoidal, with a voltage dependence of
      23 mV per e-fold change in VpkCm, and maximum slope within the physiological
      range of OHC resting potentials. This indicates that the cell is poised to
      respond maximally to changes in resting potential. 4. The kinetics of prepulse
      effects are slow compared with motility-related gating current kinetics. High
      resolution measurement of membrane capacitance (Cm) using two voltage sinusoids
      indicates that shifts in VpkCm induce Cm changes with time courses fitted by two
      exponentials (tau0, 0.070 +/- 0.003 s; tau1, 1.28 +/- 0.07 s; A0, 1.54 +/- 0.13
      pF; A1, 1.51 +/- 0.13 pF; means +/- s.e.m. ; n = 22; step from +50 to -80 mV).
      Recovery of prepulse effects exhibits a similar time course. 5. Prepulse effects
      are resistant to intracellular enzymatic digestion, to fast intracellular calcium
      buffers, and to intracellular pressure. Through modelling, we indicate how the
      effect may be explained by an intrinsic voltage-induced tension generated by the
      molecular motors residing in the lateral membrane.

PMID- 9625880
TI  - Importance of basolateral K+ conductance in maintaining Cl- secretion in murine
      nasal and colonic epithelia.
AB  - 1. Epithelia lining the nasal passages and descending colon of wild-type and
      cystic fibrosis (CF) mice were examined by the short-circuit current technique.
      Additionally, intracellular Ca2+ ion determinations were made in nasal epithelial
      cells. Forskolin produced anion secretory currents in wild-type and CF nasal
      epithelia. It produced similar effects in wild-type colonic epithelia, but not in
      colonic epithelia from CF mice. 2. After electrogenic Na+ transport was blocked
      with amiloride and electrogenic Cl- secretion was stimulated with forskolin, the
      ability of K+ channel blockers to inhibit the forskolin-induced Cl- current was
      determined. The order of efficiency for nasal epithelium was: Ba2+ > clofilium
      >>> TEA = azimilide >>> trans-6-cyano-4-(N-ethylsulphonyl-N-methylamino)-3
      hydroxy-2, 2-dimethyl-chromane (293B) = charybdotoxin, whereas for the colonic
      epithelium the order was: Ba2+ = 293B >>> azimilide = TEA >>> clofilium =
      charybdotoxin. 3. 1-Ethyl-2-benzimdazolinone (1-EBIO) was able to generate large
      Cl--secretory currents in colonic epithelia which were partially sensitive to
      charybdotoxin, with the remaining current being inhibited by 293B. In nasal
      epithelia 1-EBIO produced only a small transient effect on current. 4. Forskolin
      released intracellular Ca2+ in nasal epithelial cells; this activity was
      attenuated when more powerful Ca2+-releasing agents were applied first. 5. It is
      concluded that an action on basolateral cAMP-sensitive K+ channels is an
      important determinant of the maintained responses to forskolin in nasal and
      colonic epithelia, in addition to the effects on the cystic fibrosis
      transmembrane conductance regulator (CFTR) in the apical membrane. In CF nasal
      epithelia the activation of calcium-activated chloride channels (CACs)
      substitutes for the effect on CFTR. On the basis of the different orders of
      potency of the blocking agents and the differential response to 1-EBIO it is
      concluded that the cAMP-sensitive K+ channels are different in the airways and
      the gut.

PMID- 9625881
TI  - Inhibitory influence of the ipsilateral motor cortex on responses to stimulation
      of the human cortex and pyramidal tract.
AB  - 1. The ability of the primary motor cortex (M1) to modulate motor responses in
      ipsilateral hand muscles seems to be important for normal motor control and
      potentially also for recovery after brain lesions. It is not clear which pathways
      mediate this ipsilateral modulation. Transcallosal connections have been
      proposed, but are known to be sparse between cortical hand motor representations
      in primates. The present study was performed to determine whether descending
      ipsilateral modulation of motor responses might also be mediated below the
      cortical level in humans. 2. A paired-pulse protocol was used, in which motor
      evoked potentials (MEPs) were produced by cortical transcranial magnetic
      stimulation (cTMS) or by electrical stimulation of the pyramidal tract at the
      level of the pyramidal decussation (pdTES), in both preactivated and relaxed hand
      muscles. Paired stimuli were applied at various interstimulus intervals (ISIs)
      between 2 and 100 ms. The conditioning stimulus (CS) was always magnetic, and
      delivered to the M1 ipsilateral to the target hand, prior to the test stimulus
      (TS). The magnetic TS was delivered to the M1 contralateral to the target hand;
      the electrical TS was applied through electrodes placed over the mastoid process
      bilaterally. Further experiments included cortical electrical stimulation and H
      reflexes. The MEP amplitudes were averaged separately for each ISI and the
      control condition (no CS), and expressed as a percentage of the unconditioned
      response. 3. Conditioning stimulation of the ipsilateral M1 resulted in
      significant inhibition of magnetically evoked MEPs, and also of MEPs produced by
      pdTES. Inhibition occurred at ISIs between 6 and 50 ms, and was observed in
      preactivated and relaxed muscles. Higher CS intensities caused greater inhibition
      of both cTMS- and pdTES-evoked MEPs. 4. While the conditioning effects on
      magnetically evoked muscle responses could be explained by a transcallosal
      mechanism, the effects on pdTES-evoked MEPs cannot, because they are elicited
      subcortically and are therefore not susceptible to inhibitory mechanisms
      transmitted at the cortico-cortical level. 5. In conclusion, the present results
      provide novel evidence that the inhibitory influence of the human M1 on
      ipsilateral hand muscles is to a significant extent mediated below the cortical
      level, and not only through cortico-cortical transcallosal connections. They
      point to a concept of inhibitory interaction between the two primary motor
      cortices that is relayed at multiple levels along the neuroaxis, thus perhaps
      providing a structurally redundant system which may become important in case of
      lesions.

PMID- 9625882
TI  - Central projection of proprioceptive information from the wrist joint via a
      forearm 'muscle' nerve in the cat.
AB  - 1. Peripheral nerves arising in joint capsules are known to contain a
      'contaminating' contribution from muscle afferent fibres. In the present report
      we provide the first electrophysiological evidence that some joint afferent
      fibres may take an 'ectopic' path to the central nervous system via a nearby
      muscle nerve. 2. Experiments were conducted in anaesthetized cats in which a
      distal extension of the indicis proprius nerve was observed to project beyond its
      own muscle to the dorsal surface of the wrist joint capsule which is also
      supplied by the 'classic' wrist joint nerve, a branch of the dorsal interosseous
      nerve. Both the proximal and distal segments of the indicis proprius nerve were
      exposed for recording, by means of silver hook electrodes, while each segment
      remained in continuity. 3. Individual wrist joint afferent fibres with receptive
      fields on the dorsal surface of the joint capsule could be identified
      electrophysiologically within the distal segment of the indicis proprius nerve.
      In each of these cases the same fibre could also be identified at the proximal
      recording site. The identity of each of these simultaneously recorded units was
      established (1) by the short fixed interval between their times of spike
      occurrence, (2) from the exact correspondence of the capsular receptive field for
      the simultaneously recorded spikes, and (3) by the unfailing correlation in the
      presence, or absence, of the distally and proximally recorded spikes in
      association with either manual or controlled stimulation of the wrist joint
      capsule. Most joint afferent fibres identified with this projection path were in
      the group II range of conduction velocities and had conventional properties but
      group III fibres also appeared to be represented. 4. The present demonstration
      that some joint afferent fibres may be located within 'muscle' nerves emphasizes
      the importance of activating deep inputs, of joint or muscle origin, by adequate
      stimulation of the peripheral receptors in order to examine selectively the
      central actions of either source of input. Electrical stimulation of the
      peripheral nerves may lead to interpretative ambiguities.

PMID- 9625883
TI  - Mechanisms underlying reduced maximum shortening velocity during fatigue of
      intact, single fibres of mouse muscle.
AB  - 1. The mechanism behind the reduction in shortening velocity in skeletal muscle
      fatigue is unclear. In the present study we have measured the maximum shortening
      velocity (V0) with slack tests during fatigue produced by repeated, 350 ms tetani
      in intact, single muscle fibres from the mouse. We have focused on two possible
      mechanisms behind the reduction in V0: reduced tetanic Ca2+ and accumulation of
      ADP. 2. During fatigue V0 initially declined slowly, reaching 90 % of the control
      after about forty tetani. The rate of decline then increased and V0 fell to 70 %
      of the control in an additional twenty tetani. The reduction in isometric force
      followed a similar pattern. 3. Exposing unfatigued fibres to 10 microM
      dantrolene, which reduces tetanic Ca2+, lowered force by about 35 % but had no
      effect on V0. 4. In order to see if ADP might increase rapidly during ongoing
      contractions, we used a protocol with a tetanus of longer duration bracketed by
      standard-duration tetani. V0 in these three tetani were not significantly
      different in control, whereas V0 was markedly lower in the longer tetanus during
      fatigue and in unfatigued fibres where the creatine kinase reaction was inhibited
      by 10 microM dinitrofluorobenzene. 5. We conclude that the reduction in V0 during
      fatigue is mainly due to a transient accumulation of ADP, which develops during
      contractions in fibres with impaired phosphocreatine energy buffering.

PMID- 9625884
TI  - Mitochondrial oxidative function in human saponin-skinned muscle fibres: effects
      of prolonged exercise.
AB  - 1. The influence of prolonged exhaustive exercise on mitochondrial oxidative
      function was investigated in ten men. 2. Muscle biopsies were taken before and
      after exercise and mitochondrial respiration investigated in fibre bundles made
      permeable by pretreatment with saponin. 3. After exercise, respiration in the
      absence of ADP increased by 18 % (P < 0.01), but respiration at suboptimal ADP
      concentration (0.1 mM) and maximal ADP-stimulated respiration (1 mM ADP) remained
      unchanged. 4. In the presence of creatine (20 mM), mitochondrial affinity for ADP
      increased markedly and respiration at suboptimal ADP concentration (0.1 mM) was
      similar (pre-exercise) or higher (post-exercise; P < 0.05) than with 1 mM ADP
      alone. The increase in respiratory rate with creatine was correlated to the
      relative type I fibre area (r = 0.84). Creatine-stimulated respiration increased
      after prolonged exercise (P < 0.01). 5. The respiratory control index (6.8 +/-
      0.4, mean +/- s.e.m.) and the ratio between respiration at 0.1 and 1 mM ADP (ADP
      sensitivity index, 0.63 +/- 0.03) were not changed after exercise. The
      sensitivity index was negatively correlated to the relative type I fibre area (r
      = -0.86). 6. The influence of exercise on muscle oxidative function has for the
      first time been investigated with the skinned-fibre technique. It is concluded
      that maximal mitochondrial oxidative power is intact or improved after prolonged
      exercise, while uncoupled respiration is increased. The latter finding may
      contribute to the elevated post-exercise oxygen consumption. The finding that the
      sensitivity of mitochondrial respiration for ADP and creatine are related to
      fibre-type composition indicates intrinsic differences in the control of
      mitochondrial respiration between fibres.

PMID- 9625885
TI  - Electromyographic study of the contractile and electrical properties of the human
      triceps surae muscle in a simulated microgravity environment.
AB  - 1. The effects of 7 days of simulated space flight, achieved with the technique
      of 'dry' water immersion, on human triceps surae muscle function have been
      investigated. 2. The maximal voluntary contraction (MVC) was reduced by 33.8 % (P
      < 0.01) while the electrically evoked maximal tetanic contraction force (Po)
      decreased by 8.2 % (P > 0.05). This suggests that most of the force loss is due
      to a reduction in motor drive. 3. The decrease in Po was associated with a small
      increase in maximal rates of tension development (7.2 %). The twitch tension (Pt)
      was not significantly changed and the Pt : Po ratio was decreased by 8.7 % after
      immersion. 4. A standard fatigue test, consisting of sixty 1 s intermittent
      isometric contractions (50 impulses s-1) separated by 1 s rest decreased tetanic
      force to approximately 60 % of initial values, but force reduction was not
      significantly different before and after immersion: the fatigue index was 36.2 +/
      5.4 % before and 38.6 +/- 2.8 % after immersion (P > 0.05). Whilst there were
      similar changes in mechanical output between control and disused muscles, there
      were differences in the pattern of electrical activity.

PMID- 9625886
TI  - Bladder motility and efferent nerve activity during isotonic and isovolumic
      recording in the cat.
AB  - 1. Bladder motility and pelvic nerve efferent activity were recorded in
      anaesthetized cats under isotonic or isovolumic conditions. In isotonic
      conditions the bladder was connected to a reservoir and fluid entering or leaving
      the bladder was monitored for 8 min using different heads of pressure (isotonic
      recording). Under isovolumic conditions fixed volumes were injected into the
      bladder and pressure changes recorded (micturition contractions). 2. In isotonic
      conditions, at low pressures the bladder filled to a roughly constant level, and
      then developed small amplitude oscillatory contractions. At higher pressures,
      after the initial filling, the bladder contracted, expelling part of its volume.
      Depending on the pressure this contraction was either sustained or led to a
      gradual expansion of the bladder. In both cases transient periods of expansion
      were superimposed. In contrast after an initial slow build up, the efferent nerve
      activity increased reaching a sustained level of activity during which transient
      decreases in rate were seen. 3. The firing frequency of the efferent nerve
      activity during the sustained phase increased as the intravesical pressure was
      raised until a plateau was reached at high pressures. The plateau pressure
      (Pplateau) in a bladder was positively correlated with the peak pressure reached
      by the bladder during micturition contractions under isovolumic conditions,
      suggesting that micturition contractions were produced by the maximum output of
      the reflex pathway. 4. Section of the hypogastric nerves had relatively little
      effect, but additional section of the pelvic nerves abolished the contractile
      phase of the bladder response to filling, and resulted in continuous filling of
      the bladder. 5. The transient bladder expansions (duration, 3-33 s) seen when the
      innervation was intact were closely related to the transient decreases in
      efferent nerve activity, suggesting involvement of a central inhibitory
      mechanism. The threshold pressure for triggering transient expansions was similar
      to the pressure shown to activate myelinated afferent fibres. 6. Under isovolumic
      conditions the frequency of micturition contractions increased with increasing
      vesical volume, and the relaxed interval between contractions shortened. This
      response could also be evoked by stimulation of the central cut end of the pelvic
      nerves, suggesting that the central inhibitory mechanism could also be active
      during isovolumic conditions.

PMID- 9625887
TI  - Control of motility patterns in the human colonic circular muscle layer by
      pacemaker activity.
AB  - 1. This study characterized the electrical and mechanical activities of human
      colonic muscle strips obtained from either the ascending, descending or sigmoid
      colon of patient volunteers during elective colon resections. 2. Rhythmic
      contractile activity was observed in colonic circular muscle strips in the
      absence of external stimuli. This activity persisted in the presence of atropine,
      phentolamine, propranolol, tetrodotoxin and Nomega-nitro-L-arginine but was
      abolished by nifedipine. 3. The activity of whole circular muscle (WCM) was
      compared with that of the myenteric half (MCM), the submucosal half (SCM) and the
      interior (ICM) of the circular muscle layer. WCM exhibited a prominent 2-4
      contractions min-1 contractile pattern which was also present in strips of SCM.
      In contrast, MCM and ICM exhibited slow (0.3-0.6 contractions min-1), long
      duration contractions with superimposed higher frequency contractions (17-18
      contractions min-1). 4. Resting membrane potential (Vm), recorded at various
      positions through the thickness of WCM strips did not differ and averaged -50 mV.
      5. Slow waves were observed in 83 % of muscles. They averaged 12 mV in amplitude,
      9.4 s in duration and had a frequency of 2-4 contractions min-1. Slow waves were
      greatest in amplitude near the submucosal edge and decreased with distance away
      from this edge. Each slow wave was associated with a transient contraction. 6.
      Near the myenteric edge, rapid fluctuations of Vm with a mean frequency of 18
      contractions min-1 were recorded in 67 % of muscles. Spiking activity was common
      and was superimposed upon slow waves and rapid Vm fluctuations. 7. In summary,
      slow waves were identified in the human colonic circular muscle layer which arise
      at or near the submucosal edge. These electrical events give rise to a 2-4
      contractions min-1 contractile rhythm which is characteristic of the intact
      muscle layer. Thus, the nature and spatial organization of pacemaker activity in
      the human colon bears significant resemblance to other animal models, such as the
      dog and pig.

PMID- 9625888
TI  - Renal haemodynamic responses to exogenous and endogenous adenosine in conscious
      dogs.
AB  - 1. Adenosine has been suggested to be the mediator of a metabolic feedback
      mechanism which transfers acute changes in the tubular load into opposite changes
      in renal blood flow (RBF). The goal of the present experiments was to assess the
      importance of endogenously formed adenosine as a 'homeostatic metabolite' during
      short-term changes in metabolic demand. 2. In nine chronically instrumented
      conscious foxhounds, both the direct effects of adenosine injections (10, 30 and
      100 nmol) into the renal artery and the temporal changes of RBF after short renal
      artery occlusions (15, 30 and 60 s duration), the most widely used experimental
      model to study the metabolic feedback mechanism in vivo, were studied. 3.
      Intrarenal bolus injections of adenosine (10, 30 and 100 nmol) induced dose
      dependent decreases of RBF (RBF: -34 +/- 5, -59 +/- 4 and -74 +/- 4 %,
      respectively). This vasoconstrictor effect of adenosine was significantly larger
      (RBF: -51 +/- 4, -68 +/- 4 and -83 +/- 3 %, respectively) when the dogs received
      a low salt diet. 4. The post-occlusive responses were characterized by a
      transient hyperaemia with no detectable drop of RBF below the preocclusion level.
      The post-occlusive responses were affected neither by changes in local
      angiotensin II levels, nor by intrarenal infusions of hypertonic NaCl or blockade
      of A1 adenosine receptors. 5. When intrarenal adenosine levels were elevated by
      infusion of the adenosine uptake inhibitor dipyridamole, a transient, although
      weak, post-occlusive vasoconstriction was detected. 6. In summary, the present
      data demonstrate that adenosine acts as a potent renal vasoconstrictor in the
      conscious dog. The endogenous production of adenosine during short-lasting
      occlusions of the renal artery, however, appears to be too small to induce a post
      occlusive vasoconstrictor response of RBF. These results suggest that a metabolic
      feedback with adenosine as 'homeostatic metabolite' is of minor importance in the
      short-term regulation of RBF in the conscious, unstressed animal.

PMID- 9625889
TI  - Meeting the needs of those infected and affected by HIV/AIDS.

PMID- 9625890
TI  - Strategies for providing care and support to children orphaned by AIDS.
AB  - As a result of the severe HIV/AIDS epidemic in sub-Saharan countries such as
      Zimbabwe, where between 25-30% of the adult population are estimated to be
      infected, there are a growing number of orphans requiring care and support.
      Traditionally, orphans have been absorbed within the extended family but this is
      becoming more difficult because of the large number of young adults dying. The
      burden of care and support is falling on the very young and the very old. A
      number of strategies have been introduced to provide this care and support.
      Institutions, though popular, are very expensive to run, have limited capacity
      and only really cater for physical needs. Interventions which simply react to
      those who present to them may not reach the most needy and may encourage
      dependency. Community-based orphan care has been identified as the best and most
      cost-effective way of caring for orphans. An example of a community-based orphan
      visiting programme is presented. In the last six months of 1996, the FOCUS
      programme's 88 volunteers made a total of 9,634 visits to 3,192 orphans in 798
      families at an average cost of US+1.55 per visit. The key elements of such
      programmes have been identified. They need to be implemented by a community-based
      organization (CBO) within a defined community. Volunteers should be selected from
      within the community. They need to be trained and supported as they enumerate
      orphans, identify the most needy and carry out regular visits. The volunteers
      should keep records of all their activities. These records can then be used as a
      basis for monitoring the programme. In order to cope with the increasing number
      of orphans in resource-poor settings like Zimbabwe, it is essential that such
      programmes be replicated and scaled up. This not only an economic necessity but
      is also a way of providing appropriate and effective services to those who need
      them.

PMID- 9625891
TI  - Today's children--challenges to child health promotion in countries with severe
      AIDS epidemics.
AB  - Recent declines in infant and child mortality rates (IMR and CMR) are being
      reversed due to AIDS. Greatest impacts are in southern African countries with
      severe HIV epidemics and lower non-AIDS IMR/CMR. Zimbabwe and Zambia's IMR were
      estimated to be 40% and 30% higher in 1996; CMR by 2010 was projected to increase
      fourfold in Zimbabwe, threefold in Botswana and to double in Kenya and Zambia due
      to AIDS. HIV indirectly impacts children through orphanhood, TB and poverty. By
      1996, life expectancy fell to 36 in Zambia, 42 in Zimbabwe and 40 in Uganda. One
      third of children may become vulnerable after maternal orphanhood since elderly
      and juvenile caregivers are frequently uninformed about nutrition, oral
      rehydration, immunization and diagnosing serious illness. Resurgence of adult and
      paediatric TB affects children through increasing orphanhood and increased child
      mortality. AIDS-induced poverty among survivors leads to deterioration in
      children's health and increased vulnerability of adolescent survivors to HIV
      infection. The situation is set to worsen, especially in communities experiencing
      the cumulative impact of repeated parental deaths. Reducing the number and
      vulnerability of children and adolescents becoming HIV infected and increasing
      support to affected children are important strategies to improve child health in
      countries with severe epidemics.

PMID- 9625892
TI  - The impact of counselling on HIV-infected women in Zimbabwe.
AB  - The objective of this study was to examine the impact of counselling provided for
      HIV-infected women in Zimbabwe. Qualitative research was used for data
      collection. In total, 44 women were heard; most were members of an HIV support
      group. Doctors and nurses play an important role in the first counselling
      session, because tests to diagnose HIV-infection are done in the hospital.
      Interviewed women mention slow disclosure of status as the most comforting way to
      hear the news. The HIV-infected women experience strong emotions directly after
      diagnosis. Counselling at this moment is of major importance to reduce fear and
      can prevent suicide. Women should be prevented from discovering their status on
      their own. Counselling given once is found not to be effective. First, if only
      one counselling session is given, the women may not hear or remember all that is
      said. Second, in case of depression, access to counselling is important and it
      appears that periods of depression return frequently. Support groups play an
      important role in providing this continuous counselling. Another advantage of the
      counselling provided by HIV-positive women of a support group is that the
      counsellors function as examples.

PMID- 9625893
TI  - The socio-cultural contexts of sexually transmitted diseases in South Africa:
      implications for health education programmes.
AB  - Sexually transmitted diseases (STDs) are widespread in South Africa and
      contribute to the growing HIV epidemic. As an important step in curtailing the
      spread of STDs, this study explores STD patients' illness representations within
      its socio-cultural context, particularly gender relationships. In-depth
      interviews were conducted with Xhosa- and Zulu-speaking patients in clinics in
      Cape Town, Western Cape (N = 67) and in rural areas of Kabokweni, Mpumalanga (N =
      21) The findings suggest that STD patients' illness representations are
      reflections of their socio-cultural understanding of disease and of culturally
      defined gender relations. This, in turn, impacts on their general perceptions of
      the cause of STDs, their perceptions of the risk of contracting STDs, them
      entering and using formal and traditional medical treatment and on their ideas of
      prevention. Thus, healthy behaviours need to be facilitated through multiple
      educational strategies focusing on an improved understanding of the cause of the
      STD in its context of gender relations, the development of interpersonal and
      technical skills, as well as focusing on cues for action.

PMID- 9625894
TI  - Counselling gay men with multiple loss and survival problems: the bereavement
      group as a transitional object.
AB  - When AIDS is becoming a chronic disease, gay men with multiple loss experiences
      can easily turn into a forgotten group of widowers. Due to new medical treatment
      HIV-infected gay men are living longer and also have to deal with loss and
      surviving. This paper argues in favour of group grief therapy for multiple loss
      and survival problems, within the scope of peer support in the gay community
      during the AIDS era. In this group psychotherapy special attention is given to
      the influence of a low gay self-esteem on the grief process and surviving
      strategies.

PMID- 9625895
TI  - HIV/AIDS and the legislature: an international comparison.
AB  - This paper examines the legislative response to the AIDS epidemic. It goes beyond
      a mere overview and tries to give an insight into the chronology of the
      legislative reaction as well as its contents. For this, the legal instruments of
      217 jurisdictions were analyzed. A global chronological pattern of legislative
      reaction could be observed. Concerning the contents of legislation, legislatures
      seem to combine the public health interests with the interests, rights and
      responsibilities of individuals. This insight into the legislative reaction to
      AIDS can help us to predict and understand legislative responses to future
      epidemics.

PMID- 9625896
TI  - Adapting an effective primary care provider STD/HIV prevention training
      programme.
AB  - Sexually acquired human immunodeficiency virus (HIV) infection continues to be
      the major source of HIV infection in the USA. Preventing sexual transmission of
      HIV can be accomplished through patient behaviour change. Such behaviour change
      can also decrease risk of other sexually transmitted diseases (STDs) and unwanted
      pregnancies, both far more common problems than HIV infection. Primary care
      physicians and other providers can increase patients' safe sex practices by
      conducting effective sexual risk assessment (RA) and risk reduction (RR)
      counselling, but physicians both infrequently and incompletely do sexual RA and
      RR. A programme was developed to improve primary care physicians' prevention
      practice using Simulated Patient Instructors (SPIs) and mailed educational
      materials. Programme evaluations showed improved sexual RA and RR practice both
      by self-report as well as by observation by Simulated Patient Evaluators (SPEs).
      This paper briefly reviews these findings and then presents adaptations made to
      improve the programme's content, decrease its cost and increase its availability
      for training many other care providers. Evaluation of the adapted programme
      indicates that content and training methods are highly regarded by a diverse
      array of trainees. To disseminate the modified programme beyond the local area, a
      Train-the-Trainer programme and manual have been developed, including discussion
      of recruiting, training and using SPIs for sexual risk reduction. Wider use of
      this training, as well as more effective and more readily available STD/HIV
      prevention training, are needed to attain national goals of provider clinical
      prevention practice.

PMID- 9625897
TI  - A matter of methods: perspectives on the role of the British general practitioner
      in the care of people with HIV/AIDS.
AB  - This paper is a critique of, and a comment on, the debate about the role of
      British general practitioners (GPs) in HIV care. We argue that (1) this debate is
      conducted around arguments which leave significant aspects of GPs' contribution
      undocumented and unnoticed, and that (2) research has contributed to this
      omission. The paper reviews the history of the debate about GPs' involvement in
      HIV care and argues that social research using structured survey methods has
      reinforced the continuing negative image of GP care. The paper draws on an
      ethnographic research project in Lothian (Scotland) which found that many people
      with HIV strongly valued their ongoing personal relationship with their GP.
      People with HIV also valued the hospital-based outreach system which provided
      reliable and high quality care, but sometimes experienced the associated
      interprofessional information sharing and discussion as invasive and controlling.
      Their GP relationship was valued because it was outside this hospital-based
      system of care. The paper concludes by suggesting that future developments in GP
      care should build on this positive aspect of the GP-patient relationship.

PMID- 9625898
TI  - Non-use of condoms by prostitute women.
AB  - Ethnographic research among Glasgow female prostitutes working in street, sauna,
      flat, escort agency and "sugar daddy" sectors investigated prostitutes' accounts
      of the occasions in which condoms were not used for penetrative sexual
      encounters. Such occasions were a minority of commercial sex encounters and a
      majority of private sex encounters. Although prostitutes saw condom use as
      inappropriate in private sexual relationships this was not, as has been
      suggested, an aid to relationship interpretation as either private or commercial.
      Condoms in commercial sex were seen as routine tools of the trade, and hence
      emerged as emblems of prostitution. These emblematic qualities were found in turn
      to produce both challenges to condom use from customers and opportunities for
      prostitutes to manipulate customer relations by judicious suspension of condom
      application. Both norms of gendered role-play and prostitute status were
      highlighted as threatening condom use in some situations, while prostitute status
      could also be used as the basis of rational argument for condom use in others.
      Relational issues such as familiarity or a desire to communicate trust were at
      the forefront in explanations of condom non-use. Perceptions of physical power
      and the authority to permit or withhold sexual service or profit were determining
      influences crucial in condom use negotiation.

PMID- 9625899
TI  - Do nurses avoid AIDS patients? Avoidance behaviours and the quality of care of
      hospitalized AIDS patients.
AB  - To examine whether AIDS patients are stigmatized by nurses providing their care a
      study was conducted with 100 matched AIDS and general medical (GM) patients in
      two university and two community hospitals. Quality of care and avoidance
      behaviours were measured by direct, systematic observation during a concurrent 12
      hour period. Stigmatizing attitudes of nurses were measured using standardized
      instruments of homophobia, fear of AIDS and attitudes toward illicit drug use.
      Nurses made more eye contact and touched AIDS patients more frequently then GM
      patients, however these differences did not reach the level of statistical
      significance They spent significantly more time with AIDS patients (W = 3134.0, p
      = 0.012). Whether or not nurses were fearful of HIV infection, were homophobic or
      held negative feelings about drug use made no difference in the level of care
      provided to AIDS patients, but did for GM patients. However, avoidance behaviours
      were associated with lower quality of care across all patients regardless of
      diagnosis. Hierarchical regression models demonstrated that increased time spent
      with patients and higher percentage positive of verbal mannerisms were associated
      with an increase in the quality of patient care. Provision of physical care
      showed the least amount of variation between patients in general. It was
      concluded that nurses' attitudes had no impact on whether or not AIDS patients
      were shunned by nurses. The provision of psychosocial care showed the greatest
      variation and seemed more sensitive to individual nurses' attitudes. The quality
      of care received by the overwhelming majority of patients could only be termed
      adequate. Nurses exhibited the greatest caution when performing procedures with
      patients whose HIV status was unknown. The AIDS population studied were mostly
      well-educated, homosexual men. Whether these results would be replicated with a
      different population of patients is as yet unknown.

PMID- 9625900
TI  - HIV follow-up care at a London teaching hospital.
AB  - Counselling around all stages of HIV infection is important for those infected
      and affected with HIV disease. Partner notification may promote safer sexual
      practices and increase HIV-related social support which might in turn prompt the
      psychological adjustment to a terminal illness. This paper describes the
      counselling service used at the Royal Free Hospital's HIV Unit and explores the
      notification patterns of an HIV diagnosis to family, partners and significant
      others. Retrospective data was abstracted from counselling notes for 100 HIV
      positive patients attending the unit for the first time between November 1995 and
      March 1996. The majority of the sample were gay males who tested from 1995
      onwards. Most patients tested at the Same Day Testing Clinic (SDTC) were gay
      males. In contrast, patients who tested elsewhere were more likely to be females.
      Rates of pre- and post-test counselling were high and the majority (85%) of the
      patients had notified a family member, partner or significant other. Few
      significant differences in demographics were found between those who had notified
      others and those who had not, although patients who had been diagnosed more
      recently were less likely to have notified other family members. The implication
      of the results are discussed.

PMID- 9625901
TI  - Psychological distress and burnout among buddies: demographic, situational and
      motivational factors.
AB  - Work-related psychological distress (burnout) is a probable cause of drop-out
      among emotional support volunteers (buddies) who work with people living with
      AIDS. In addition to the emotional suffering and disruption to both the buddy and
      the buddied, burnout has significant cost implications for voluntary
      organizations in terms of training and recruitment. The aim of this study was to
      identify the demographic, situational and motivational factors associated with
      burnout among buddies with the intention of identifying individuals at risk at
      the recruitment stage. A cross-sectional single cohort postal questionnaire study
      design was used. All buddies registered with the Terrence Higgins Trust, a non
      profit making organization set up in the UK to provide education about HIV/AIDS
      and care for people affected by the virus, were invited to participate.
      Psychological morbidity was measured with the Hospital Anxiety and Depression
      Scale, burnout with the Maslach Burnout Inventory and motivation was assessed
      using the Calvert Motivation Checklist. Information on the buddy relationship and
      the demographic details of each buddy was also collected. Of 586 questionnaires
      distributed, 324 (55%) were returned. More than 24% of buddies were classified as
      probable cases of burnout on one or more of the MBI scales but this is lower than
      has been reported in medical and nursing staff working with people living with
      AIDS. Although a number of demographic, situational and motivational factors were
      associated with burnout, logistic regression models were unable to identify a
      useful proportion of individuals at risk. It was concluded that although burnout
      is an important psychological factor in retaining volunteers, it was not possible
      to identify individuals at risk of burning out either from their self-reported
      motivations or from demographic factors.

PMID- 9625902
TI  - Community support to families living with HIV in London: an agency overview.
AB  - In 1996 a structured questionnaire, relating to services provided, was completed
      by 12 agencies providing support to families with HIV in London. A wide range of
      information, practical and therapeutic services were available from these
      agencies but these usually had a primary focus on supporting the adults in these
      families. Only one agency had been set up specifically to offer a direct service
      for children within their own home or community. Services for children within
      most agencies consisted of organized child care or social activities, often
      provided to enable parents to access other services at the centre. Concern was
      frequently expressed that the normal and emotional needs, especially of older
      children, were not being met. Many children attending events at these agencies
      were unaware of the diagnosis or the reasons for attending these centres.
      Implications are discussed on how future development of services in the voluntary
      and statutory sector will need to address the specific and changing needs of
      infected and affected children.

PMID- 9625903
TI  - AIDS counselling for low-risk clients.
AB  - This study addresses the counselling of heterosexual men with low-risk behaviour
      who, voluntarily or involuntarily, take an HIV test. If such a man tests
      positive, the chance that he is infected can be as low as 50%. We study what
      information counsellors communicate to clients concerning the meaning of a
      positive test and whether they communicate this information in a way the client
      can understand. To get realistic data, one of us visited as a client 20 public
      health centres in Germany to take 20 counselling sessions and HIV tests. A
      majority of the counsellors explained that false positives do not occur, and half
      of the counsellors told the client that if he tests positive, it is 100% certain
      that he is infected with the virus. Counsellors communicated numerical
      information in terms of probabilities rather than absolute frequencies, became
      confused and were inconsistent. Based on experimental evidence, we propose a
      simple method that counsellors can learn to communicate risks in a more effective
      way.

PMID- 9625904
TI  - The effects of establishment practices, knowledge and attitudes on condom use
      among Filipina sex workers.
AB  - The findings for a baseline assessment for a community-based HIV/STD prevention
      intervention for commercial sex workers (CSWs) and managers of the establishments
      that employ them in the Philippines is presented in this study. CSW knowledge,
      attitudes, behaviours and establishment policies concerning HIV prevention were
      assessed. Baseline assessments are part of an iterative process that will be used
      to modify the planned intervention. The preliminary findings point to the
      importance of an intervention that stresses changes in establishment policies and
      expectations as a means of reducing risk behaviours associated with HIV/STD
      transmission.

PMID- 9625905
TI  - Co-infection with Mycobacterium tuberculosis and HIV in high risk clinical care
      setting in Rhode Island.
AB  - We assessed the extent to which co-infection with HIV and Mycobacterium
      tuberculosis (Mtb) was diagnosed at several high risk clinical care sites from
      1992 to 1994 to determine whether surveillance for co-infection was performed.
      Information on PPD skin testing, HIV status, and HIV risk exposures was extracted
      from records at HIV clinics in Rhode Island and a large database (HIV sites) and
      from records at the state TB clinic and the Rhode Island Health Department (TB
      sites). At the HIV sites, 34 of 1,408 HIV infected subjects were newly diagnosed
      with Mtb infection in the study period. At the TB sites, 16 of 1,389 subjects
      with newly diagnosed Mtb infection or disease were identified as HIV infected.
      Eighty per cent of the records reviewed for this study were incomplete. Hispanic
      subjects were at higher risk of being identified as co-infected at the HIV sites.
      At the TB sites, US-born subjects were at higher risk of being identified as co
      infected Recommendations for high risk individuals include yearly tuberculosis
      skin testing. Adherence to these guidelines in selected high-risk clinical care
      sites in Rhode Island was substandard during the study period; the importance of
      Mtb screening was demonstrated in this study. Identification of groups that are
      at higher risk of having HIV and Mtb co-infection identified may enable health
      care providers to improve testing and prevention of tuberculosis at high risk
      clinical care settings.

PMID- 9625907
TI  - Survey of food safety awareness among HIV positive individuals.
AB  - A survey was carried out by personal interview to assess the awareness of basic
      food hygiene and food safety amongst 77 HIV-positive individuals attending a
      single hospital. There was some confusion and lack of knowledge about aspects of
      food storage and despite the fact that 74% of subjects had modified their diet
      since learning their HIV status (mainly for nutritional reasons) only 25%
      reported receiving information on food safety. Of the subjects interviewed 96%,
      66% and 23% were aware of the risks of infection from Salmonella, Listeria
      monocytogenes and Cryptosporidium, respectively; although most were not aware of
      the UK Government's advice on the consumption of eggs, soft cheese, pate and cook
      chill foods. Over 40% of those interviewed reported that they did not drink tap
      water (most drank bottled water instead), but few were aware of infections
      potentially transmitted through water. Although pets represent a potential source
      of a wide variety of infectious agents, there was a high level of awareness of
      this problem. This study highlights the need for improving the availability of
      information on food hygiene and infections acquired through food and water to HIV
      positive individuals.

PMID- 9625906
TI  - The development of a community-based family HIV service.
AB  - This paper describes the development of a community-based family HIV clinic in
      south London, an area with one of the highest rates of HIV seroprevalence in the
      UK. The King's family clinic was developed by broadening existing
      interdisciplinary services for women with HIV, utilizing the strengths of
      community-based paediatric care as well as integrating paediatric support from
      acute hospital-based services. Different models of care for children infected or
      affected by HIV and problems encountered in developing the service, including
      ethical dilemmas, and current activity are discussed.

PMID- 9625908
TI  - Randomized comparison of intramuscular artemether and intravenous quinine in
      adult, Melanesian patients with severe or complicated, Plasmodium falciparum
      malaria in Papua New Guinea.
AB  - An open-label, randomized, controlled trial was used to compare the safety and
      efficacy of intramuscular artemether (a loading dose of 3.2 mg/kg, followed by
      1.6 mg/kg daily for 4 days) and intravenous quinine (a loading dose of 20 mg
      quinine dihydrochloride/kg, followed first by 10 mg/kg every 8 h, each injection
      taking 4 h, for at least 48 h, and then oral quinine for a total of 7 days) in
      the management of strictly defined severe/complicated malaria in Melanesian
      adults. Four (12%) of the 33 patients who enrolled and completed follow-up died
      (one of the 15 who received artemether and three of the 18 who received quinine).
      Overall, cerebral malaria was uncommon (6%) whilst jaundice was common (76%). The
      time taken to clear 50% of parasites was less in those treated with artemether
      (median = 8 h; range = 2-24 h) than in the patients given quinine (median = 14 h;
      range = 2-25 h; P = 0.05). Temperature defervescence was also quicker in those
      treated with artemether (median = 32 hours; range = 20-112 h) than in those in
      the quinine group (median = 48 h; range = 28-88 h; P = 0.034). Hypoglycaemia was
      not observed in any patient treated with artemether but complicated therapy in 11
      (79%) of the 14 patients given quinine who had not had pre-treatment spontaneous
      hypoglycaemia. No serious adverse effects were attributable to artemether. The
      Plasmodium falciparum infections observed during the 1 month of follow-up, in
      three patients who had received artemether and two who had been given quinine,
      were probably due to recrudescence. Plasmodium vivax parasitaemias were also
      observed during follow-up, in one or two patients in each treatment group.
      Artemether appears safe in Melanesian adults and is probably as effective as
      intravenous quinine in the treatment of severe or complicated falciparum malaria.

PMID- 9625909
TI  - An evaluation of the effects of intermittent sulfadoxine-pyrimethamine treatment
      in pregnancy on parasite clearance and risk of low birthweight in rural Malawi.
AB  - The prevalence of infection with malarial parasites and the incidence of anaemia
      and delivery of infants with low birthweight (LBW) were investigated in 575
      Malawian mothers who received one, two or three doses of sulfadoxine
      pyrimethamine (SP) during pregnancy. All the subjects were enrolled at their
      first antenatal visit and all delivered at hospital. The prevalence of Plasmodium
      falciparum infection at first antenatal visit was 35.3% in primigravidae and
      13.6% in multigravidae (P < 0.001). Mean haemoglobin concentration was
      significantly lower in primigravidae than in multigravidae (8.8 v. 9.5 g/dl; P <
      0.001). Of the 233 women tested for HIV infection, 18.8% of the primigravidae and
      23.7% of the multigravidae were seropositive. At delivery, there was no
      significant difference in parasite prevalence in peripheral or placental blood
      between women who had received one or two antenatal doses of SP. The
      multigravidae who had received two doses of SP had higher mean haemoglobin
      concentrations than those who had received just one (P = 0.009) [this difference
      was not seen in the primigravidae (P = 0.92)]. However, linear regression
      analysis indicated that the haematinic supplements given to the subjects
      contributed more to this increase in haemoglobin concentration than the SP. The
      mean birthweights were higher, and incidence of LBW lower in babies born to primi
      and multi-gravidae who had received two or three doses of SP treatment than those
      seen in babies born to women who had had just one dose (P < 0.03 for each). The
      odds ratio for LBW in primigravidae compared with multigravidae decreased from
      3.2 to 1.0 as the number of SP doses increased from one to three. The benefit of
      three doses (compared with none) was equivalent to the population-attributable
      risk of LBW in primigravidae being reduced from 34.6% to 0%. Subjects who were
      seropositive for HIV were twice as likely to give birth to LBW babies as the
      other subjects. The use of SP was not associated with maternal side-effects or
      perinatal complications. The present results indicate that multiple doses of SP
      taken during pregnancy will lead to a highly significant reduction in the
      incidence of LBW in infants born to primigravidae, even if the women have HIV
      infections. This reduction is observable even when parasite prevalence at
      delivery is high because of re-infections in late pregnancy; reduction in
      parasite prevalence earlier in pregnancy, as the result of SP treatment, leads to
      improved foetal growth.

PMID- 9625910
TI  - Treatment of visceral leishmaniasis with sodium stibogluconate in Sudan:
      management of those who do not respond.
AB  - Almost all (98%) of 1593 visceral leishmaniasis (VL) patients treated with sodium
      stibogluconate (Pentostam; Wellcome) in Sudan between 1989 and 1995 and follow-up
      responded well to treatment. However, the other 33 patients, all of whom were
      seronegative for HIV, showed partial or no response. The two main causes of
      unresponsiveness were primary drug resistance (39.3%) and low drug dosages given
      at peripheral dispensaries (30.3%). All of those who had been sub-optimal doses
      were cured when adequate doses of the drug were given. A third cause was
      concurrent disease, particularly pulmonary tuberculosis (18%). With treatment of
      the concurrent disease, patients responded well to Pentostam. Eight patients who
      failed to respond to repeated courses of Pentostam did not benefit from
      pentamidine or sterol inhibitors. Three of these patients responded to liposomal
      amphotericin B, two responded to splenectomy in association with Pentostam
      therapy, and three died. Pentostam, given in adequate doses, still appears to be
      the drug of choice for the treatment of VL in the Sudan Liposomal amphotericin B
      is a suitable second-line drug.

PMID- 9625911
TI  - The latex agglutination test: standardization and comparison with direct
      agglutination and dot-ELISA in the diagnosis of visceral leishmaniasis in India.
AB  - Laboratory diagnosis of visceral leishmaniasis (VL) is usually based on the
      detection of Leishmania amastigotes in samples of bone marrow or splenic aspirate
      obtained by invasive procedures. Serological tests serve as a useful adjunct and
      are especially valuable in early or highly immune cases where amastigotes may be
      too scanty to be seen easily. The direct agglutination test (DAT) is generally
      considered the most suitable of the four types of tests currently employed (IFAT,
      counter immuno-electrophoresis, ELISA and DAT). However, the latex agglutination
      test (LAT) was recently reported to be a rapid and sensitive screening tool for
      VL and one which could be carried out at the patient's bedside. Further
      standardization and evaluation of LAT has now revealed that although it is
      comparable with DAT and dot-ELISA in terms of sensitivity it is far inferior
      because of cross-reactivity with other infections. This lack of specificity makes
      LAT unsuitable for routine diagnosis of VL even though it is rapid and sensitive.
      DAT still appears to be the best choice as a diagnostic tool, as it is very
      specific and does not require expensive equipment or reagents or much technical
      competence and the result can be visually interpreted. These merits make DAT very
      suitable for the diagnosis of VL in endemic areas of India.

PMID- 9625912
TI  - Comparative efficacy of meglumine antimoniate and aminosidine sulphate, alone or
      in combination, in canine leishmaniasis.
AB  - Thirty-two domestic dogs naturally infected with Leishmania infantum and showing
      viscero-cutaneous signs of canine leishmaniasis were treated with aminosidine
      sulphate (11 dogs) meglumine antimoniate (10 dogs) or with a combination of the
      two drugs (11 dogs) for 21 consecutive days. Clinical and laboratory assessments,
      made on day 21 and at 2, 4 and 6 months after initiation of treatment, showed
      that the drug combination gave the best score in terms of clinical efficacy,
      incidences of early clinical relapse, any clinical relapse or apparent
      parasitological cure, and reduction in parasite densities in bone-marrow and
      lymphnode aspirates (even though a lower dose of antimonial was used in the
      combination than for antimonial monotherapy). For each of the above parameters,
      however, the higher efficacy of the drug combination was not statistically
      significant, probably because of the large variations caused by using naturally
      infected animals of various ages and breeds.

PMID- 9625913
TI  - A survey of amoebic infection in the Wonji area of central Ethiopia.
AB  - An epidemiological survey to characterize Entamoeba histolytica/E dispar isolates
      from 123 human subjects was carried out in the Wonji area of Central Ethiopia,
      where an increased incidence of amoebic infection has been reported. In a
      randomized, coproparasitological study, 93 (75.6%) of the subjects were found
      positive for at least one species of intestinal parasite: 14 (15.1%) harboured
      only one species and 79 (84.9%) were infected with at least two species. In-vitro
      culture in Robinson's medium revealed amoebic parasites in 52 (82.5%) of the 63
      cases tested. Of the 29 amoebic isolates successfully stabilized, cloned and
      characterized by Sargeaunt's electrophoretic technique, 27 (93.1%) were of E.
      dispar zymodemes (19 of zymodeme I, two each of zymodemes III, V and XI, and one
      each of zymodemes X and XV) and two (6.9%) were of E. histolytica (zymodeme
      XIII).

PMID- 9625914
TI  - The distribution of Schistosoma japonicum eggs in faeces and the effect of
      stirring faecal specimens.
AB  - Experiments were performed to determine whether Schistosoma japonicum eggs are
      randomly dispersed in faeces and the effect of stirring faecal specimens prior to
      sampling. For each of 13 patients infected with S. japonicum, eggs were counted
      in 150 subsamples from a single stool specimen, using the Kato-Katz smear
      technique. Eggs were non-randomly distributed in all 13 stools, and showed an
      aggregated distribution. In most patients there were significant differences in
      the distribution of eggs between the centre and the surface of the stool.
      Stirring of the stool prior to sampling decreased the variability of counts.

PMID- 9625915
TI  - Peri-portal fibrosis of the liver due to natural or experimental infection with
      Schistosoma mansoni occurs in the Kenyan baboon.
AB  - The chronic granulomatous inflammation that occurs during schistosomiasis mansoni
      and its reparative healing lead to hepatic fibrosis, with subsequent portal
      hypertension (a life-threatening sequela). In the murine model, granuloma
      modulation invariably leads to formation of fibrous tissue and disposition of
      extracellular matrix. Typically, < 10% of patients infected with Schistosoma
      mansoni progress to clay-pipe-stem fibrosis. Similar fibrosis occurs in
      chimpanzees during experimental infections. Although previous studies of
      schistosomiasis mansoni in Kenyan baboons have failed to demonstrate appreciable
      liver fibrosis, classical peri-portal fibrosis has now been observed in the
      livers of three yellow baboons (Papio cynocephalus cynocephalus) with natural S.
      mansoni infections and three olive baboons (P. c. anubis) with experimental
      infections after each was challenged with 1000 S mansoni cercariae. The peri
      portal fibrosis was indicated by marked fibroblast accumulation, increased
      collagen deposition, bile-duct hyperplasia and blood-vessel proliferation. The
      lesions were more severe in the naturally infected baboons than in those
      experimentally infected. No accompanying portal hypertension, ascites or
      portocaval anastomosis was noted in any of the animals. The development of the
      baboon as a model for chronic human schistosomiasis mansoni may be feasible.

PMID- 9625916
TI  - Onchocerciasis control in Uganda: how can self-sustaining, community-based
      treatment with ivermectin be achieved?
AB  - In Uganda, the control of onchocerciasis by mass treatment with ivermectin
      (Mectizan) began in 1990 and has expanded greatly since 1992. The parties
      involved in the programme are the Uganda Ministry of Health and its National
      Onchocerciasis Task Force, the Mectizan Donation Programme, the African Programme
      for Onchocerciasis Control, a number of non-governmental development
      organizations and the communities where the disease is endemic. Their aim is to
      make the programme self-sustaining, without further outside aid, within a period
      of 12 years. The methodology of the ivermectin-distribution programme, based on
      community-directed treatment, is outlined; the constraints under which the four
      co-operating parties have to work are described and the effects of the social
      changes produced by community-directed distribution are discussed, all in terms
      of influence on the achievement of a programme that will be able to sustain
      itself without the need for outside aid.

PMID- 9625917
TI  - Norwalk virus infection in Venezuela.
AB  - The presence of antibodies against Norwalk virus (NV) was studied in sera from
      different Venezuelan populations, using an enzyme immuno-assay (EIA) based on
      recombinant NV protein. Antibodies to NV were found in 47%-53% of urban subjects
      from Caracas, 83% of rural subjects from the west of the country, and 73%-93% of
      Amerindian subjects. The prevalences found in the rural and Amerindian groups
      were significantly higher than that in the urban group. Although about 50% of the
      children studied were seropositive for NV by the age of 5 years, only four (0.4%)
      of 1120 faecal samples from children with diarrhoea which were tested for the
      presence of NV antigen by sandwich EIA were found positive. An increase of at
      least 4-fold in the titre of anti-NV IgA was found in three (5%) of 61 pairs of
      sera taken during and 1 month after an acute episode of diarrhoea not due to
      rotavirus. NV was therefore not a predominant aetiological cause of gastro
      enteritis in young children in Venezuela between 1993 and 1995, although it can
      be the cause of diarrhoea in infants.

PMID- 9625918
TI  - Aeromonas hydrophila soft-tissue infection as a complication of snake bite:
      report of three cases.
AB  - Aeromonas hydrophila soft-tissue infection has been associated with fish and
      reptile bites. There have bee three recent cases from Brazil of abscesses
      complicating snake bites in which A. hydrophila was isolated from the purulent
      exudates. One of the snakes responsible for the bites was a specimen of Bothrops
      moojeni, and the others were most probably also lance-headed vipers. These snakes
      have a local necrotizing, myotoxic, oedema-inducing venom that must have favoured
      the multiplication in the injured tissue of A. hydrophila strains, which were
      probably present in the mouth, fangs or venom of the snakes. The use of a
      tourniquet by two of the patients probably worsened the local envenoming, and
      contributed to the occurrence of soft-tissue infection. The patients had a good
      outcome after the abscesses were incised and drained, and after being treated
      with chloramphenicol. Chloramphenicol appears to be a good alternative for the
      empirical treatment of soft-tissue infection complicating snake bite in Brazil,
      because: it is active against the majority of the anaerobic and aerobic bacteria
      found in these abscesses, including A. hydrophila; it can be administered by the
      oral route; and its is inexpensive. Suitable alternatives are cotrimoxazole or
      fluoroquinolones, to which aeromonads are usually susceptible in vitro,
      associated with antibiotics, such as clindamycin and metronidazole, with an anti
      anaerobic spectrum.

PMID- 9625919
TI  - Morphometrics of domestic Panstrongylus rufotuberculatus in Bolivia.
AB  - The trend to domesticity in Triatominae may represent a transitionary phase,
      towards increasing vectorial importance in the transmission of Chagas disease to
      humans, and requires sustained entomological surveillance. Although generally
      considered a sylvatic species, Panstrongylus rufotuberculatus has been recently
      captured inside human dwellings in the provinces of Nor Yungas and Munecas in the
      Department of La Paz, Bolivia, providing evidence of this species' ability to
      colonise domestic habitats. The results of previous research on domestic and
      sylvatic specimens of other species of Triatominae indicate that morphometrics
      could be used to monitor this adaptive process. The most likely cause of
      differences seen in the size and shape of bugs from domestic colonies of P.
      rufotuberculatus from two neighbouring villages in Bolivia is probably genetic
      drift rather than environmental influences. Comparison with allopatric sylvatic
      specimens, including the holotype of P. rufatuberculatus, showed a general
      reduction in size from sylvatic to domestic specimens.

PMID- 9625920
TI  - Infection rates of Leishmania donovani in Phlebotomus orientalis from a focus of
      visceral leishmaniasis in eastern Sudan.

PMID- 9625921
TI  - The differential identification of Blastocystis hominis cysts.

PMID- 9625922
TI  - Studies on falciparum malaria with atomic-force and surface-potential
      microscopes.
AB  - Atomic-force microscopy (AFM) was used to examine the structure of the knobs on
      unfixed erythrocytes infected with Plasmodium falciparum. Although each knob
      appears as a cone when chemically fixed and viewed by transmission electron
      microscopy, AFM revealed that each consisted of two subunits, and that, unlike
      the remainder of the erythrocytic surface, which was negatively charged, the knob
      surface has a positive electrical charge. Each of these factors might be central
      to the phenomenon of cyto-adherence in falciparum malaria.

PMID- 9625923
TI  - The leishmaniases as model zoonoses.
AB  - Of the 374 species of parasite recorded as naturally infecting Homo sapiens, all
      but some 40 are zoonotic. A classification of human parasites is proposed, based
      on the role of H. sapiens in the maintenance of suprapopulations. Categories
      range from 1, for which man is irrelevant to the persistence of the species, to
      4, which includes the small number of host-specific forms. The classification is
      illustrated by various species of Leishmania, and these are used to illustrate
      various host-parasite systems. The 'Wells effect' is proposed, to describe the
      protection of host populations by their parasites.

PMID- 9625925
TI  - Anaemia in malaria control: a practical approach.
AB  - Mortality from malarial anaemia and malarial infection in those who are already
      anaemic yet have some degree of compensation is now beginning to receive the
      attention it deserves. It is of particular concern in Africa and especially in
      young children and pregnant women. The asymptomatic parasitaemia remaining after
      poor response to full antimalarial treatment may lead to life-threatening
      anaemia; as drug-resistant strains of the malarial parasite proliferate this is
      becoming increasingly important. It is now possible to estimate haemoglobin
      levels, simply, cheaply, easily and safely, using a haemoglobin colour scale
      which is being developed by the World Health Organization. The potential and
      practical value of this scale in malaria-control programmes was demonstrated in a
      small, preliminary trial in 1995. Estimation of anaemia should become an
      additional parameter in the traditional malariometric survey. Haemoglobin
      concentrations should also be taken into consideration in the management of
      malaria patients at the primary-care level, particularly in deciding whether a
      patient should be referred to an appropriate treatment centre. The accurate
      prediction of clinical outcome of malaria and anaemia, and indication of the
      appropriate action (determined by a case-based reasoning device) should be
      possible in the near future.

PMID- 9625924
TI  - Research notes from the Onchocerciasis Chemotherapy Research Centre, Ghana.
AB  - Brief notes are given on drugs which have been tested at the Onchocerciasis
      Chemotherapy Research Centre at Tamale and Hohoe and found to have activity
      against Onchocerca volvulus. Ivermectin in single doses as high as 800
      micrograms/kg was found to be no more effective than the standard dose of 150
      micrograms/kg. The benzimidazole carbamates, mebendazole and albendazole, differ
      in their effects on O. volvulus. The former has microfilaricidal effects and is
      toxic to developing embryos surrounded by an egg shell but not the stretched
      microfilariae. Albendazole has no microfilaricidal activity but is toxic to all
      intra-uterine stages. The reasons for these differences are unclear. Early
      studies with amocarzine are described; the maximum tolerable dose is 20 mg/kg and
      the predominant activity, against the microfilariae, is marked only at doses
      greater than 12 mg/kg. None of the drugs tested has macrofilaricidal activity.

PMID- 9625926
TI  - Reclaiming the essentials of Akufo.
AB  - Herbert Gilles' study of disease and environment at Akufo in Nigeria around 1960
      was an early example of an integrated and detailed approach to understanding the
      health of a small group of people. Subsequent studies on a larger scale have
      focused on particular diseases or on the provision of medical care. The primary
      health-care movement has tended in practice to neglect the material environment.
      Medical anthropological work has returned to detailed studies of processes in
      small communities. There is a need to return to looking at the overall health and
      disease pattern of small communities, together with their environment and human
      behaviour, to get a coherent understanding. The formulation of interventions
      appropriate to this understanding will be more difficult.

PMID- 9625927
TI  - Clinical pharmacology and malaria.
AB  - The role of clinical pharmacology in improving the prevention and treatment of
      malaria is reviewed. A series of general and specific issues is discussed,
      concentrating on risk-benefit and cost-effectiveness. The techniques of clinical
      pharmacokinetics play an important role in the optimal use of drugs and this is
      illustrated by studies on quinine and proguanil. In discussing amodiaquine
      toxicity, the role of the pharmacologist and the chemist in designing out drug
      toxicity lends hope for producing a new generation of antimalarial drugs.

PMID- 9625928
TI  - Health and foreign policy: an American view.
AB  - Health and humanitarian complications of conflicts and disasters are,
      increasingly, the bases for international intervention. Concerns about widespread
      starvation, the spread of epidemic diseases, and a whole range of human-rights
      violations are now central factors in foreign affairs. Emphasising health issues
      can offer an innovative approach to the resolution of apparently intractable
      problems. Identifying the common concerns, of even the most bitter enemies, can
      provide an initial basis for dialogue and lead to diplomatic initiatives.
      Further, the methodology of public health and the metaphors of medicine provide a
      needed structure for a new era in post-Cold-War international relations; this
      would include an emphasis on preventive diplomacy that, the author argues, is as
      essential for the United States as it is for the United Nations.

PMID- 9625929
TI  - Teaching tropical medicine: a personal view in perspective.
AB  - Over the last few decades, European courses in which 'classical' tropical
      medicine (i.e. parasitology, entomology, and clinical aspects of tropical
      diseases) is taught have largely become anachronisms. Most countries in the
      tropics have their own medical schools and few have much need of expatriate
      doctors. There do, however, appear to be other ways in which Europeans may still
      help improve health in the tropics. One is to control the quality of the
      expatriate nurses who are still in demand in the tropics (often as cheaper,
      generally less demanding substitutes for doctors). This may be achieved by only
      training the best, insisting they spend some time after graduation gaining
      maturity before they leave for the tropics, ensuring they realise that their
      clinical skills will probably be inferior to their local counterparts in the
      tropics, and encouraging them to continue studying once abroad. The second way
      Europeans may help is to change the bias of their courses from teaching to
      training. There seems little doubt that the intellectual personalities of the
      brightest young men and women in the tropics often develop far better when they
      spend a period in a foreign environment, especially when they are allowed to
      function within a team, with trainees and trainers from other countries. Some
      'international' courses may offer such benefits, especially if closely tailored
      to the needs of the trainees and their home countries.

PMID- 9625930
TI  - Leishmaniasis in Malta and the Mediterranean basin.
AB  - Leishmaniasis is a public-health problem in most countries bordering the
      Mediterranean littoral. In Malta, where the disease has been recognized for many
      years, Phlebotomus perniciosus is the established vector and dogs act as
      reservoir hosts. Visceral leishmaniasis (VL) was the only form of the disease
      recorded in Malta until the early 1980s, when cutaneous leishmaniasis (CL) was
      recognized. Although the incidence of CL has recently increased, the overall
      numbers of cases of leishmaniasis have markedly decreased since the 1960s. Prior
      to 1963, almost all cases were aged < 10 years. Although leishmaniasis in Malta
      is still mainly a disease of children, adult cases are increasingly being
      recognized. HIV-VL co-infection is being seen more and more frequently in the
      Mediterranean basin, especially in Spain, France and Italy. During diagnosis,
      leishmaniasis should be suspected on the basis of the clinical picture in endemic
      areas and on the travel history of those patients from non-endemic areas. In
      Malta, VL and CL are generally confirmed by detection of the parasites in smears,
      of bone-marrow or, rarely, splenic aspirates and of lesions, respectively.
      Antimonials are the standard therapeutic agents for VL, although liposomal
      amphotericin B is a very effective but expensive alternative, with no significant
      adverse effects. In Malta, the treatment of choice for CL is cryotherapy.

PMID- 9625931
TI  - In pursuit of a better quality of life through the Basic Minimum Needs Programme:
      the Afghan experience.
AB  - This paper reports the outcome of work on integrated community development
      carried out in two villages in the Behsood district of Nangarhar province,
      Afghanistan, where the Basic Development Needs (BMN) model of community
      development was introduced in the last quarter of 1995. It describes the
      conceptual framework and the socio-political constraint under which the BMN
      development process evolved and was pursued. It also provides a detailed account
      of the methodology adopted, the results of the BMN survey, the socio-economic
      profile of the villages and the underlying causes of the problems. The paper
      gives an expose of the set of potential interventions and solutions chosen by the
      community to solve their problems.

PMID- 9625932
TI  - The epidemiology of malaria.
AB  - Epidemiologists have recently paid greater attention than in the past to the
      epidemiology of clinical malaria as opposed to the epidemiology of malarial
      infection. This change of emphasis has been stimulated in part by the need for
      better clinical definitions of malaria in the evaluation of control measures such
      as insecticide-treated materials and malaria vaccines. Methods of determining
      mortality from malaria and of defining severe and uncomplicated malaria have been
      devised. The limited data available indicate that malaria-attributable mortality
      and the incidence of severe malaria do not increase with an increase in the
      entomological inoculation rate above a threshold value, an observation that has
      important implications for the likely long-term effects of attempts to contain
      malaria through vector control. Study of the epidemiology of severe malaria in
      Africa has shown different epidemiological patterns for the two most frequent
      forms of this condition: cerebral malaria and severe malarial anaemia. Severe
      malarial anaemia is seen most frequently in areas of very high malaria
      transmission and most frequently in young children. In contrast, cerebral malaria
      predominates in areas of moderate transmission, especially where this is
      seasonal, and it is seen most frequently in older children. Study of patients
      with uncomplicated malaria has established the relationship between fever and
      parasite density and has demonstrated ways of defining fever thresholds.
      Algorithms have been developed to help in the diagnosis of malaria in the absence
      of parasitological confirmation but this approach has proved difficult because of
      the overlap in symptoms and signs between malaria and other acute febrile
      illnesses such as pneumonia.

PMID- 9625933
TI  - The scourge of HIV-related tuberculosis: a cohort study in a district general
      hospital in Malawi.
AB  - Malawi is similar to a number of other African countries in having an escalating,
      HIV-related, tuberculosis (TB) epidemic. A prospective study was carried out to
      determine the pattern of disease and HIV serostatus in unselected, adult, TB
      patients consecutively admitted to a large, district general hospital in Zomba
      (in the Southern region of Malawi). Clinical details were obtained, from the
      district TB register, for the 714, adult TB patients, aged > or = 15 years, who
      were registered with the district TB officer between 1 July and 31 December in
      1995. Patients were counselled, and offered HIV testing using an ELISA and
      particle agglutination test. Concordant HIV-test results were available for 686
      (96%) of the subjects: 547 (80%) of these were HIV-seropositive and 139
      seronegative. The HIV-positive patients were significantly younger than the HIV
      negative patients and significantly more HIV-positive patients were males (P <
      0.05 for each). The proportions of HIV-positive subjects who were new patients,
      had been previously treated for TB, had pulmonary TB (PTB), had smear-positive
      PTB or had different types of extrapulmonary TB were similar to those of the HIV
      negative. A high percentage of an unselected cohort of adult TB patients admitted
      to a district, general hospital in Malawi, particularly of the younger age groups
      was therefore HIV-positive. The pattern of disease was uninfluenced by the HIV
      serostatus. The large number of cases registered emphasises the severity of the
      current epidemic of TB in Malawi and its impact upon young adults.

PMID- 9625934
TI  - Meningococcal disease in Africa.
AB  - Neisseria meningitidis (the meningococcus) is responsible for endemic and
      meningococcal disease in Africa. Meningococci are placed into 12 serogroups based
      on their capsular polysaccharide antigens. Group-B meningococci are responsible
      for sporadic endemic disease. In the meningitis belt of sub-Saharan Africa, the
      large spreading epidemics which occur every 5-10 years are usually caused by
      group-A meningococci, with attack rates of 400-500/100,000 population. In the
      last epidemic, infection spread from the original meningitis belt to Kenya,
      Uganda, Rwanda, Zambia and Tanzania. Most cases of meningococcal disease are of
      meningitis and meningococcal septicaemia is a rare presentation except in South
      Africa. It is important to exclude meningococcal septicaemia since this carries
      the highest mortality (up to 75%). Treatment involves intravenous chloramphenicol
      (or intramuscular, oily chloramphenicol), a drug which is preferable to
      penicillin because penicillin-resistant meningococci have already emerged in
      Africa. Dexamethasone treatment of meningococcal meningitis is unproven and may
      even be deleterious in developing countries. Prevention of epidemic meningococcal
      disease could be achieved by mass vaccination with protein-conjugate, group-A and
      -C polysaccharides, but these new vaccines are likely to be expensive.

PMID- 9625935
TI  - Of sick turkeys, kwashiorkor, malaria, perinatal mortality, heroin addicts and
      food poisoning: research on the influence of aflatoxins on child health in the
      tropics.
AB  - Similarities between the geographical and climatic prevalences of kwashiorkor and
      of exposure to dietary aflatoxins, and between the biochemical, metabolic and
      immunological derangements in kwashiorkor and those in animals exposed to
      aflatoxins, prompted investigation of the associations between kwashiorkor and
      aflatoxins. Studies in Africa in the 1980s indicated a role for these toxins in
      the pathogenesis of the disease. Paediatric cases of kwashiorkor are less prone
      to severe Plasmodium falciparum malaria than normal children. In mice infected
      with P. berghei, aflatoxin exposure inhibits parasite growth and ameliorates
      morbidity. Aflatoxins occur in < or = 40% of samples of breast milk from tropical
      Africa, usually as low concentrations of the relatively non-toxic derivatives of
      aflatoxin B1 (AFB1) but sometimes as high concentrations of the very toxic AFB1.
      This could explain kwashiorkor in breast-fed babies. Aflatoxin exposure occurs in
      > or = 30% of pregnancies in tropical Africa and the toxins are often in cord
      blood, sometimes at extremely high concentrations. Aflatoxins are now
      incriminated in neonatal jaundice and there is circumstantial evidence that they
      cause perinatal death and reduced birthweight. Aflatoxin-induced immunosuppresion
      may explain the aggressive behaviour of HIV infection in Africa. There are
      similarities between observations on HIV cases in Africa and those on heroin
      addicts in Europe, where 'street' heroin is frequently contaminated with
      aflatoxin. Aflatoxins were found in 20% of random urine samples from heroin
      addicts in the U.K. and the Netherlands. Aflatoxins have also been incriminated
      in episodes of food poisoning which have been associated with serious morbidity
      and mortality, particularly among young children.

PMID- 9625936
TI  - The direct agglutination test: a non-specific test specific for the diagnosis of
      visceral leishmaniasis?
AB  - Serology has an important role to play in the diagnosis of the severe clinical
      syndrome of visceral leishmaniasis (VL). The direct agglutination test (DAT), a
      simple agglutination test which requires no laboratory facilities, has become the
      preferred test, particularly for field studies. The nature of the antigens
      responsible for the agglutination of leishmanial promastigotes by the serum of VL
      patients is not known. A series of experiments which provide some clues to the
      molecular basis for the test and which indicate that there might be more in DAT
      than meets the eye is reported.

PMID- 9625937
TI  - The placenta and malaria.
AB  - Placental malaria is recognized as a common complication of malaria in pregnancy
      in areas of stable transmission, and is particularly frequent and severe in
      primigravidae. Many hypotheses, based on a systemic or local failure of the
      immunological response to malaria, have been proposed to explain the 'preference'
      of the parasites for replication in the placenta. Some of the hypotheses are
      briefly reviewed here, with a particular focus on the discovery of an uncommon
      subpopulation of Plasmodium falciparum which can adhere and massively sequester
      in the placenta. Histologically, placental malaria is characterized by the
      presence of parasites and leucocytes within the intervillous spaces, pigment
      within macrophages, fibrin deposits and trophoblasts, proliferation of
      cytotrophoblastic cells and thickening of the trophoblastic basement membrane.
      The exact mechanisms leading to placental changes and determining the observed
      impairment of materno-foetal exchange are incompletely understood. Parasites are
      unlikely to be directly responsible for the placental pathology, but leucocytes,
      through the production of non-chemotactic cytokines, might be associated with the
      thickening of the trophoblastic basement membrane, and might cause a mechanical
      blockage of oxygen and nutrient transport across the placenta. There is sound
      epidemiological evidence that placental malaria determines low birthweight,
      mainly mediated by intrauterine growth retardation, and increases the risk of
      death and disease during the first year of life. Antimalarial chemoprophylaxis
      significantly reduces placental malaria and prevents the development of low
      birthweight. It is likely that, in areas of high endemicity, the placenta is
      where the drama of maternal malaria is mostly played. A deeper understanding of
      the mechanisms involved in this process is of key importance in the design of
      protective interventions which are effective and acceptable during the gestation
      period.

PMID- 9625938
TI  - Malaria and mortality: some epidemiological considerations.
AB  - Malaria can, a priori, kill on its own ('direct' malaria mortality) or in
      conjunction with some other cause(s) ('indirect' malaria mortality). There are
      three distinct approaches to the measurement of malaria mortality: (1)
      measurement of malaria-specific mortality (based on attributing each death to a
      single cause) or its surrogate, the admission rate for life-threatening malaria;
      (2) measurement of the reduction in all-cause mortality after removal (or near
      removal) of malaria; and (3) the estimation of the malaria mortality required to
      explain the observed frequency of the HbS gene. There is a strong indication that
      approaches (2) and (3) yield estimates of total (direct and indirect) malaria
      mortality which are at least twice as high as those obtained using approach (1),
      which probably measures mostly direct malaria mortality. There is currently a
      controversy about the long-term impact on mortality of reducing the intensity of
      malaria transmission from 'high' to 'intermediate', given the expected loss of
      immunity. Certain geographical comparisons (of the results of 'nature's
      experiment') indicate that, when the intensity of transmission is high, the
      incidence of life-threatening malaria falls. However, the seasonal variation in
      the intensity of transmission decreases with increases in the intensity; low
      seasonal variation is probably beneficial, allowing a smoother transition from
      passive to active immunity, but is unlikely to be reversed by preventive
      measures. It also seems likely that geographical comparisons produce estimates of
      predominantly direct mortality, which might not run in parallel with the indirect
      mortality. A tentative numerical exploration of the problem, using a simple
      demographic model, indicates that, if indirect malaria mortality is important and
      the other causes of death are concentrated in early life, the long-term impact on
      all-cause mortality of reducing exposure (although less than the short-term) will
      probably always be beneficial, even if there is some increase in direct malaria
      mortality.

PMID- 9625939
TI  - Patterns of change in vector-borne diseases.
AB  - The statuses of vector-borne diseases have changed over recent years. How a few
      such diseases have changed and the primary causes of change (urbanization,
      increased conflict, changes in water-resource management, ecological and
      environmental change, and reduced health service resourcing) are the subjects of
      the present review. The key impacts which these primary causes have on selected
      vectors and the infections they transmit are tabulated. The success of vector
      control programmes against onchocerciasis and Chagas disease is discussed, and
      the methods used to evaluate the epidemiological impact of such controls are
      described. Bednet programmes for control of malaria are recognized as a potential
      future means of reducing morbidity and mortality in children. In contrast to the
      success achieved in limiting Simulium and Triatoma populations through vertical
      programmes, control of tsetse, whilst successful in Uganda, has not been utilized
      to stem recent epidemics of sleeping sickness in resource-stressed settings in
      Central Africa. Vector-borne diseases will continue to be a problem because of
      the adaptability of vectors, the potential problems of managing effective vector
      controls within decentralized health systems, and the influence of activities
      outside the health sector itself. Changes beyond the health sector can increase
      the problem posed by a vector and increase the frequency of transmission.

PMID- 9625940
TI  - Tropical trials: the problems of research in the tropics.
AB  - Eleven scientists who, like Herbert Gilles, have spent many years in the study of
      tropical disease, responded to an inquiry about the most problematic aspects of
      conducting intervention trials in the tropics. Areas of challenge or difficulty
      that figured most frequently in the replies were: (1) the proper interests,
      involvement and perceptions of the studied community; (2) maintaining a research
      team's standards and motivation over long periods; (3) good study design; (4)
      communications; and (5) the provision of adequate remuneration and incentives to
      local scientists. Other problems mentioned included the need to translate results
      into policy, the importance of a long-term view, the correct use of controls, the
      attitudes of donors, and the influences of national and local politics. Careful
      attention must be given to these aspects in the planning and conduct of
      international research.

PMID- 9625941
TI  - Use of PCR on lymph-node sample as test of cure of visceral leishmaniasis.
AB  - When the polymerase chain reaction (PCR) was used to test lymph-node aspirates
      from 35 patients from eastern Sudan, who had had visceral leishmaniasis but were
      believed cured, leishmanial DNA was detected in samples from 14 of the patients.
      There were no significant differences between the PCR-positives and -negatives in
      terms of age, sex, spleen size, malaria status or presence of anti-Leishmania
      antibodies. However, PCR was more often positive in the patients who tested
      negative by the leishmanin skin test (LST) than in those who gave positive skin
      tests. Moreover, patients with a positive PCR and a negative LST converted more
      often to LST positivity than those with a negative PCR and a negative LST. The
      most important finding was that, during follow-up, eight (57%) of the PCR
      positives, but none of the 21 negatives, developed post-kala-azar dermal
      leishmaniasis (PKDL) In conclusion, PCR-based testing of lymph-node aspirates
      after treatment may be used as a prognostic marker for the future development of
      PKDL and may be useful in the follow-up of patients.

PMID- 9625942
TI  - Human African trypanosomiasis in south-eastern Uganda: clinical diversity and
      isoenzyme profiles.
AB  - The spectrum of clinical manifestations of trypanosomiasis in south-eastern
      Uganda is extremely wide. Isoenzyme characterization of trypanosome strains
      isolated in this area during recent epidemics of sleeping sickness has shown that
      particular clinical features of the disease can be related to the zymodeme of the
      causative parasite. For example, B17, part of the 'busoga' group of isolates and
      a zymodeme identified from central areas of Busoga during outbreaks of sleeping
      sickness, is associated with severe early features and a high frequency of
      presentation with a chancre. Isolates belonging to the 'zambezi' group, most of
      which came from areas close to the lake shores or close to the River Nile, were
      more heterogenous and were associated with significantly different clinical
      features: a more chronic, prolonged illness; more frequent presentation with
      meningo-encephalitis, and less frequent chancres. The clinical spectrum of
      infection associated with the parasites currently in circulation indicates that
      the previous endemicity and the early epidemics could be explained on the basis
      of existing zymodemes.

PMID- 9625943
TI  - An objective approach to antivenom therapy and assessment of first-aid measures
      in snake bite.
AB  - Treatment of systemic envenoming in snake-bite victims has, in the past, depended
      almost entirely on the individual clinician's experience in assessing the
      severity of envenoming. The efficacy of treatment is obviously related to the
      neutralizing potency of the antivenom used, the route by which it is administered
      and the dose. The development of enzyme immunoassays has permitted a more
      scientific appraisal, allowing estimation of circulating specific venom and
      antivenom concentrations at any time after the bite in the patient's blood. It is
      therefore possible to measure accurately the efficacy of antivenom in the
      neutralization and clearance of venom antigen. In Brazil, it appears that
      clinicians treat patients with excessive amounts of highly efficient antivenoms
      and this results in an unacceptably high incidence of reactions. In Sri Lanka,
      the use of imported, Indian antivenom is relatively ineffective in neutralizing
      the venoms of Sri Lankan snakes, demonstrating the real problem of venom
      variability within individual species. In West Africa, the improved clearance of
      venom following treatment of Echis victims with a monospecific as opposed to a
      polyspecific antivenom has been demonstrated, and new, smaller fragment, Fab
      antivenoms have been developed and are now under clinical assessment. Such
      clinically-based immunological studies should result in more efficient and
      controlled use of expensive antivenoms for treatment of systemic envenoming and
      the accurate assessment of newly designed products. Such studies also emphasise
      the importance of individual countries producing their own antivenoms for
      treatment of systemic envenoming. Likewise, the use of such objective systems now
      enables the use of first-aid measures such as tourniquets to be properly
      assessed.

PMID- 9625944
TI  - Is halofantrine still advisable in malaria attacks?
AB  - Halofantrine is an antimalarial drug which is widely prescribed for the treatment
      of infections with chloroquine-resistant strains of Plasmodium falciparum.
      Chemically, it is a phenanthrene methanol, belonging to the aryl-amino-alcohol
      family. It has recently been recognized that this drug may induce rare but
      serious, cardiotoxic effects, including lengthening of the QTc interval, 'torsade
      de pointes' and induction of late ventricular potentials. These events are
      thought to be related to a quinidine-like action of the drug. In addition, severe
      haemolytic accidents have been reported, mimicking blackwater fever and
      indicating an immunological process. As a result of these side-effects, new
      guidelines for prescription and more cautious use of halofantrine, particularly
      as a stand-by treatment for febrile access among travellers, are required.

PMID- 9625945
TI  - Cerebral malaria: clinical features, pathophysiology and treatment.
AB  - Herbert Gilles played an important role in the establishment of the Wellcome
      Mahidol University, Oxford Tropical Medicine Research Programme in Thailand in
      1979. The randomized, placebo-controlled trial of dexamethasone in cerebral
      malaria that was carried out in Chantaburi in 1980 yielded results which led to
      the abandonment of ancillary corticosteroid therapy in this disease and
      contributed to a rejection of the 'permeability hypothesis'. The clinical
      manifestations of strictly defined cerebral malaria have not been described both
      in non-immune adults in Thailand and Vietnam and in African children. Clinical
      and histopathological studies in human patients, together with laboratory studies
      of cyto-adherence, malaria 'toxin' and cytokine production have provided some
      evidence for both the 'mechanical' and 'toxin-cytokine' hypotheses to explain the
      pathophysiology of this condition. Chemotherapy is challenged by the continuing
      evolution of antimalarial resistance. Recently, the most powerful studies ever
      carried out with antimalarial drugs have demonstrated that artemether and quinine
      achieve similar case fatalities, in the range 11%-21%, and that both drugs have
      some advantages and disadvantages. Further studies are needed to define the
      efficacy and safety of prophylactic anticonvulsants and exchange transfusion in
      cerebral malaria. Cerebral malaria remains a major cause of mortality and, in
      African children, morbidity.

PMID- 9625946
TI  - Thalassaemia and malaria, revisited.
AB  - Haldane's attractive hypothesis that the high gene frequencies for thalassaemia
      in the Mediterranean population may have resulted from heterozygote advantage in
      regions where Plasmodium falciparum malaria was common in the past has been
      extremely difficult to verify at the population or experimental level. However,
      the molecular era has provided some powerful new tools to attack this old
      problem. It is now clear that the thalassaemias are the commonest monogenic
      diseases in man, with a broad distribution throughout the Mediterranean, Middle
      East, Indian sub-continent and South-east Asia. All these populations have
      specific types of thalassaemia mutations which, presumably, have arisen locally
      and been expanded by selection together with drift and founder effect. Recent
      work indicates that alpha thalassaemia provides protection against severe
      malaria. Quite unexpectedly at least some of this protection may be mediated by
      rendering very young children more susceptible to both P. vivax and P. falciparum
      malaria; such early immunization may provide some protection against the disease
      in later life.

PMID- 9625947
TI  - Artesunate suppositories: an effective treatment for severe falciparum malaria in
      rural areas.
AB  - Artesunate is a potent antimalarial agent available in oral, parenteral and
      rectal formulations. Artesunate suppositories rapidly reduce and quickly clear
      parasitaemias. The rapidity of effect, availability and convenient dosage regimen
      make artesunate in suppository form a promising treatment for severe falciparum
      malaria, particularly in rural areas where parenteral formulations are
      unavailable.

PMID- 9625948
TI  - As nurses considered the governments first year in power.

PMID- 9625949
TI  - Knowing the score.

PMID- 9625950
TI  - Centre of attention.

PMID- 9625951
TI  - Nutrition and pregnancy.

PMID- 9625952
TI  - Care in a cold climate.

PMID- 9625953
TI  - Is stress the new voodoo and stress consultants its high priests?

PMID- 9625956
TI  - The demon drink.

PMID- 9625957
TI  - Women under the influence.

PMID- 9625958
TI  - Sobering effect.

PMID- 9625959
TI  - Leading question.

PMID- 9625960
TI  - In our parents' shadow. Huntington disease.

PMID- 9625962
TI  - Face to face. Interview by Eileen Fursland.

PMID- 9625963
TI  - Rectal bleeding.

PMID- 9625964
TI  - The role of the nurse specialist in osteoporosis.

PMID- 9625965
TI  - The OK way to keep track of clients' health needs.

PMID- 9625966
TI  - Power-sharing brings greater satisfaction.

PMID- 9625967
TI  - Snapshots of the mind.

PMID- 9625968
TI  - Under pressure to update research.

PMID- 9625969
TI  - The hippo challenge.

PMID- 9625970
TI  - The management of a faecal fistula.

PMID- 9625971
TI  - A holistic approach to pressure area care.

PMID- 9625972
TI  - Short-stretch compression bandaging for lymphoedema.

PMID- 9625973
TI  - Methods of wound debridement.

PMID- 9625974
TI  - Fighting talk.

PMID- 9625975
TI  - Grace under fire.

PMID- 9625976
TI  - The paperchase.

PMID- 9625977
TI  - Skateboarding down the M1 so often seems easier than acting on sound health
      advice.

PMID- 9625978
TI  - Opportunities to reshape health policy.

PMID- 9625979
TI  - The future looks bright for health secretary Frank Dobson and health minister
      Alan Milburn.

PMID- 9625980
TI  - Caring for rape survivors.

PMID- 9625981
TI  - Wards of fear.

PMID- 9625982
TI  - Why women deserve privacy.

PMID- 9625983
TI  - Promising start but must try harder.

PMID- 9625984
TI  - Managing the airway: methods and techniques.

PMID- 9625985
TI  - Clinical risk assessment for mental health nurses.
AB  - This article proposes a risk management cycle for mental health nurses, it can be
      used as a guide to assessing and managing the risk of harm associated with people
      with mental health problems alongside systematic approaches to planning care.

PMID- 9625986
TI  - Proving that community nursing works.

PMID- 9625987
TI  - School nurses in the driving seat.

PMID- 9625988
TI  - The need for a clear policy on glove use.

PMID- 9625989
TI  - Past insights for present problems. Eileen Skellern Memorial Lecture.

PMID- 9625990
TI  - Delivery men.

PMID- 9625991
TI  - Birth of hope.

PMID- 9625992
TI  - Bullied to distraction.

PMID- 9625993
TI  - Learning together, working together.

PMID- 9625994
TI  - The non-healing diabetic foot wound: fact or fiction?
AB  - Wounds on the feet of diabetic patients are often labeled as "non-healing." This
      article discusses the basis for and the dangers of such a classification. The
      evidence suggests that if the foot has an adequate vascular supply and no
      significant infection, a plantar wound that does not heal is the result of poor
      treatment and/or poor compliance. Wounds that do not heal despite optimal
      treatment and compliance are extremely rare and need to be referred to the
      appropriate specialist for care.

PMID- 9625995
TI  - Skin tears in institutionalized elderly: an epidemiological study.
AB  - Skin tears in the elderly are a common alteration of aging skin integrity. Very
      little is found in the literature on the prevention, identification, and
      treatment of skin tears. During a six-month period, 154 skin tears were studied
      in a convenience sample of residents in a VA Nursing Home Care Unit and nine
      community nursing homes. Data were collected on demographics, medication use,
      laboratory tests, cognitive function, and activities of daily living (ADLs).
      Descriptive data on the skin tears were also collected and these tears were
      graded according to the Payne-Martin Classification System. Data analysis
      revealed an at-risk sample of very old, frail elderly who are predominantly
      women, dependent in ADLs, nutritionally compromised, and suffering from dementia.
      Risk factors associated with the occurrence of skin tears included stiffness and
      spasticity, sensory loss, limited mobility, poor appetite, polypharmacy, use of
      an assistive device, presence of ecchymosis, and a history of previous skin
      tears. Skin tears were small, occurred more frequently on the upper extremities,
      and half had no tissue loss. Most skin tears occurred in patient care bedrooms.
      The findings of this study provide an outline for the development of an at-risk
      profile, and establish the basis for educational programs for caregivers.

PMID- 9625996
TI  - The relationship between stress and pressure sore formation.
AB  - The purpose of this study was to explore the relationship between serum cortisol
      and pressure sore formation among persons over age 65 who recently relocated to a
      nursing home. Twenty-six subjects who exhibited risk for pressure sore formation
      and were free of pressure sores and diagnoses or medications known to affect
      cortisol were recruited from consecutive admissions to a nursing home. Morning
      and evening cortisol levels were assayed the first and second weeks following
      admission, and subject's skin and risk status were assessed twice weekly for five
      weeks. Subjects who developed pressure sores had significantly higher cortisol
      levels than those who did not (p < 0.02), with the greatest differences occurring
      in the second week (p < 0.002). The cortisol levels observed in subjects who
      developed pressure sores may be due to the stress of relocation, but other
      explanations are also possible. Furthermore, a causal relationship between
      cortisol and pressure sore development cannot be inferred.

PMID- 9625997
TI  - Validating the Braden Scale for the prediction of pressure ulcer risk in blacks
      and Latino/Hispanic elders: a pilot study.
AB  - The purpose of this pilot study was to examine the Braden Scale for Predicting
      Pressure Sore Risk and determine which variables predict pressure ulcer risk in
      Black and Latino/Hispanic elders. A prospective clinical design was used to
      conduct the study. Among 36 patients, 60 years of age or older, 14 (38%)
      developed a pressure ulcer. A Fisher Exact test (2-tail) revealed that, at a cut
      off score of 16, the Braden Scale significantly underpredicted those patients at
      risk for pressure ulcers (5.13 E-03). Sensitivity was 35 percent and specificity
      was 100 percent for a Braden Scale score of < or = 16.

PMID- 9625998
TI  - Beyond risk assessment: elements for pressure ulcer prevention.
AB  - Considerable emphasis has been placed on identifying individuals who are at risk
      for developing pressure ulcers. However, the generality of diagnostic
      discriminations and consequent intervention strategies may have resulted in less
      effective outcomes than otherwise would be possible. When such processes are
      carried out in a system devoid of the fundamental elements required for increased
      diagnostic/prescriptive precision and systematic improvement, practitioners are,
      at best, relegated to relying on external trial-based research to yield new "best
      practices." At worst, ineffective and costly practices continue without
      systematic evaluation and alteration. Several necessary elements of any
      empirically-based prevention system are addressed, and an attempt to integrate
      the elements into a system for field utilization is illustrated. If successful,
      the system will result in incremental improvements in the outcomes of prevention
      efforts over time.

PMID- 9625999
TI  - Soaps and detergents: understanding their composition and effect.
AB  - Soaps have been used for thousands of years as part of religious ceremonies and
      daily life. Derived from fatty acids or triglycerides (fats or oils) into their
      alkali derivatives through a process called saponification, soaps are important
      for healthcare professionals in preventing the spread of disease. Partly due to
      their alkaline nature, soaps are limited by their irritancy to the skin and their
      tendency to form insoluble and inactive salts when combined with either hard
      water or sea water. Therefore, soap alternatives or synthetic detergents have
      been developed. Detergents are classified into four groups: anionic, cationic,
      amphoteric, and non-ionic. These four groups are based on the hydrophilic
      qualities and surfactants they possess. Each group has characteristics that
      pertain to its main uses, irritancy, and toxicity. Understanding soaps and
      detergents may assist clinicians in making intelligent choices when using these
      agents on their patients as either skin cleansers or wound cleansers.
      Understanding the characteristics of soaps and detergents is especially important
      when dealing with at-risk patients such as the elderly.

PMID- 9626000
TI  - Education for health promotion and disease prevention: convince them, don't
      confuse them.
AB  - Promotion of health and prevention of disease have become some of the most
      emphasized issues of the 1990s. The government, health professionals, and private
      organizations have made the primary prevention of disease a priority. Quality
      education is a major intervention by which prevention is realized. However,
      superior quality educational offerings entail significant pre-preparation via the
      development of clear and realistic teaching/learning plans, faculty knowledge of
      educational psychology, metacognition and cognitive processing, understanding of
      cultural diversity, incorporation of adult learning principles, the use of varied
      teaching/learning strategies, and astute application of program evaluation
      skills. Educators, like nurses, physicians, and allied health professionals, must
      work with people to mutually decipher their healthcare needs and plan educational
      experiences that learners can merge with their own life experiences and
      ethnocultural perspectives. In addition, educators should use health education
      materials that match learners' literacy levels. Most importantly, such programs
      must be thoughtfully evaluated in light of the achievable goals that were
      outlined during preplanning stages. Without outcomes assessment as part of health
      promotion/disease prevention education programs, health educators are less likely
      to produce interventions that learners value and from which they truly benefit.
      Optimally, education programs about health promotion/disease prevention should
      generate long-term critical thinking processes that produce positive health
      choices, behavioral change, and healthy life styles.

PMID- 9626001
TI  - Sequential biannual prevalence studies of pressure ulcers at Allegheny-Hahnemann
      University Hospital.
AB  - To assess the prevalence, documentation and care of pressure ulcers, and the
      effect of teaching and prevention strategies in a 750-bed university hospital,
      one-day studies were conducted in 1993, 1995, and 1997. Data gathered was used to
      evaluate areas in need of improvement and find cost-effective ways to reduce the
      prevalence of pressure ulcers. The overall prevalence of ulcers decreased from 18
      percent in 1993 to 10 percent in 1995 and 1997. The prevalence of nosocomial
      ulcers decreased from 14 percent in 1993 to 8 percent in 1995 and 6 percent in
      1997. The number of nutritional consults increased from 54 percent in 1993 to 67
      percent in 1997, and more than half of all patients tested had serum albumin
      levels < 3.5 mg/dL. Skin assessments upon admission were completed in the
      majority of patients. While ulcer documentation was less than adequate for the
      majority of patients in 1993 and 1997, care measures, e.g., placement of patients
      on specialty beds or mattresses and use of dressings that provide a moist
      environment, improved considerably. The results of this study indicate that
      system-wide educational efforts aimed at all levels of patient care providers,
      and multi-specialty prevention and care efforts can reduce the prevalence of
      pressure ulcers.

PMID- 9626002
TI  - Outcomes: are clinicians read?

PMID- 9626003
TI  - The handmaidens require an adjustment in our attitudes.

PMID- 9626004
TI  - Exploring the relationship between ethics committees and the wound care
      clinician.
AB  - Ethics Committees have gained increasing popularity since the mid-1970s. This is
      likely due to the recognized need to more openly discuss the legal and ethical
      issues of clinicians and their patients. Wound care clinicians play an important
      role in the interdisciplinary care of the patient. The typical framework of a
      hospital-based Ethics Committee is described, Ethics Committees as a resource to
      the wound care clinician is presented, and the role of the wound care clinician
      as a consultant to the Ethics Committee, from an interdisciplinary perspective,
      is illustrated.

PMID- 9626005
TI  - Plantar pressures are higher in diabetic patients following partial foot
      amputation.
AB  - The purpose of this study was to compare peak plantar pressure in diabetic
      patients with and without foot-level amputation. This project was conducted as a
      case-control study. We enrolled 27 cases and 150 controls diagnosed with diabetes
      mellitus. Cases were defined as patients with a history of forefoot-level
      amputation (digit or ray amputations distal to the tarsometatarsal joint)
      secondary to an infected forefoot wound. Controls were defined as subjects that
      had never had a foot ulceration. We used a pressure platform system to evaluate
      dynamic barefoot pressure on the sole of the foot. There was no significant
      difference in vascular perfusion or body mass index between the case and control
      groups. Patients with a foot-level amputation were nearly ten times more likely
      to present with limited joint mobility or a rigid foot deformity than those
      without amputation (92.6% vs. 44.0%, p < 0.0001, X2 = 13.0, Odds Ratio = 9.8 CI =
      2.2 to 43.0). Peak plantar pressure was significantly higher for patients with
      amputations compared to controls (80.0 +/- 31.1 N/cm2, vs, 62.5 +/- 21.0 N/cm2, p
      < 0.001). Peak pressure and limited joint mobility have long been associated with
      ulceration. We conclude that increased pressure and contractures associated with
      biomechanical compensation following a partial foot amputation further increase
      plantar pressure, placing an already high-risk limb at further risk for tissue
      breakdown and reamputation.

PMID- 9626006
TI  - Microbiologic evaluation of cutaneous wounds in hospitalized dermatology
      patients.
AB  - The purpose of this study is to identify predictability of wound flora which may
      be helpful in the selection of empiric antibiotic therapy of wound infections
      while awaiting the results of bacterial cultures. Toward this end, results of an
      ongoing microbiologic surveillance of skin wound flora in hospitalized
      dermatology patients are presented. Bacterial isolates cultured from patients
      with skin wounds admitted to a tertiary care dermatology inpatient unit were
      evaluated and comparison was made to a previous survey of the same inpatient
      service done in 1992. Microbiologic evaluation of superficial skin wounds, leg
      ulcers, and pressure ulcers showed that Staphylococcus aureus was the principal
      isolate in superficial wounds (77%) compared to the equal prevalence of S. aureus
      (43%) and Pseudomonas aeruginosa (42%) cultured from leg ulcers. Cultures from
      pressure ulcers grew Proteus mirabilis as the dominant isolate. These data agree
      with previous surveillance data from the same inpatient base performed in 1992
      and support the relatively predictable wound flora cultured from skin wounds in
      our hospital inpatient unit over the 4 years surveillance period. This
      predictability can enhance empiric antibiotic selection for wound infections
      while awaiting the results of bacterial culture, and supports the value of local
      microbiologic surveillance programs in the management of wound infections.

PMID- 9626007
TI  - Use of a four-layer bandage system in the treatment of an i.v. drug abuser with
      chronic upper extremity ulcerations: a case study.
AB  - A patient with a ten-year history of heroin abuse presented to a wound healing
      clinic for treatment of multiple ulcerations to his upper arm. The largest
      measured 3.5 cm x 1.7 cm. The patient related that these wounds came from his
      i.v. heroin use. Previous treatments included iodine packed gauze, saline soaked
      fine mesh gauze, dakins solution, and wet-to-dry dressings; all treatments were
      unsuccessful. Treatment included cleansing the wound with normal saline, packing
      the ulcers with a calcium alginate rope, and wrapping the arm using a four-layer
      bandage. The dressing remained in place for 7-day time intervals. During the
      course of treatment, the patient remained heroin-free. No unscheduled dressing
      changes occurred, nor did the patient report discomfort with the dressing or
      during dressing changes. The patient was able to maintain complete range of
      motion throughout care. Complete healing was noted by day 42. The calcium
      alginate dressing combined with the 4-layer bandage system has proved successful
      in treating the patient.

PMID- 9626008
TI  - Compression bandaging effects on lower extremity peripheral and sub-bandage skin
      blood perfusion.
AB  - Laser-Doppler blood perfusion was simultaneously measured on both great toes and
      the lateral upper-calf before and during fore-foot-to-knee compression bandaging
      of one test-leg in ten vascularly healthy female volunteers. Two bandaging
      methods were sequentially used separated by a 30 minutes interval. Bandage A
      consisted of a layer of zinc impregnated gauze and an elastic wrap; bandage B had
      the elastic wrap only. Sub-bandage pressures of the test-leg were measured at
      distal and proximal lateral below-knee standardized sites. The study purpose was
      to determine the effects of moderate compression pressure achieved for bandages A
      under and distal to bandaged regions. Initial (mean +/- sem_ sub-bandage pressure
      achieved for bandages A and B were similar, being respectively 32.9 +/- 2.8 and
      28.4 +/- 3.9 mm Hg. Both bandages types were associated with significant
      reductions in test-leg toe blood perfusion amounting to 44.2 +/- 13.1 percent and
      27.5 +/- 10.5 percent for bandages A and B respectively. Contrastingly, test-leg
      sub-bandage blood perfusion did not differ from its pre-bandage baseline mean
      level for either bandage type. These findings show that a widely used bandaging
      method and a slight variant each significantly reduces distal (toe) blood
      perfusion without reducing sub-bandage skin perfusion. Absence of sub-bandage
      perfusion decreases may be related to a partially compensating reflex
      vasodilatory response, but such effects if present are inadequate to prevent
      reductions in distal perfusion. These results reinforce the need for due care and
      risk-benefit consideration with respect to therapeutic compression levels.

PMID- 9626009
TI  - Pain management in the elderly--what you should know.

PMID- 9626010
TI  - Can psych care lower cardiac costs?

PMID- 9626011
TI  - You can safely skip the LDH.

PMID- 9626012
TI  - Closing in on safer suctioning.

PMID- 9626013
TI  - A valentine in May.

PMID- 9626014
TI  - Ruptured varices! Act fast.

PMID- 9626015
TI  - Osteoporosis. When supports weaken.

PMID- 9626016
TI  - Preventing falls.

PMID- 9626017
TI  - Transmyocardial revascularization.

PMID- 9626018
TI  - Legal risks of alternative therapies.

PMID- 9626019
TI  - Extra hours don't always mean extra pay.

PMID- 9626020
TI  - Managing the aftermath of shingles.

PMID- 9626021
TI  - The right to say goodbye.

PMID- 9626022
TI  - The evolving role of the acting internship in the medical school curriculum.

PMID- 9626023
TI  - Cyclooxygenase-1 and cyclooxygenase-2 selectivity of widely used nonsteroidal
      anti-inflammatory drugs.
AB  - PURPOSE: Both isoforms of cyclo-oxygenase, COX-1 and COX-2, are inhibited to
      varying degrees by all of the available nonsteroidal anti-inflammatory drugs
      (NSAIDs). Because inhibition of COX-1 by NSAIDs is linked to gastrointestinal
      ulcer formation, those drugs that selectively inhibit COX-2 may have less
      gastrointestinal toxicity. We measured the extent to which NSAIDs and other anti
      inflammatory or analgesic drugs inhibit COX-1 and COX-2 in humans. SUBJECTS AND
      METHODS: Aliquots of whole blood from 16 healthy volunteers were incubated ex
      vivo with 25 antiinflammatory or analgesic drugs at six concentrations ranging
      from 0 (control) to 100 microM (n = 5 for each). Blood was assayed for serum
      generated thromboxane B2 synthesis (COX-1 assay) and for lipopolysaccharide
      stimulated prostaglandin E2 synthesis (COX-2 assay). In addition, gastric
      biopsies from the same volunteers were incubated with each drug ex vivo and
      mucosal prostaglandin E2 synthesis measured. RESULTS: Inhibitory potency and
      selectivity of NSAIDs for COX-1 and COX-2 activity in blood varied greatly. Some
      NSAIDs (eg, flurbiprofen, ketoprofen) were COX-1 selective, some (eg, ibuprofen,
      naproxen) were essentially nonselective, while others (eg, diclofenac, mefenamic
      acid) were COX-2 selective. Inhibitory effects of NSAIDs on gastric prostaglandin
      E2 synthesis correlated with COX-1 inhibitory potency in blood (P < 0.001) and
      with COX-1 selectivity (P < 0.01), but not with COX-2 inhibitory potency. Even
      COX-2 "selective" NSAIDs still had sufficient COX-1 activity to cause potent
      inhibitory effects on gastric prostaglandin E2 synthesis at concentrations
      achieved in vivo. CONCLUSION: No currently marketed NSAID, even those that are
      COX-2 selective, spare gastric COX activity at therapeutic concentrations. Thus,
      all NSAIDs should be used cautiously until safer agents are developed.

PMID- 9626024
TI  - Effect of long-term gastric acid suppressive therapy on serum vitamin B12 levels
      in patients with Zollinger-Ellison syndrome.
AB  - BACKGROUND AND AIMS: Long-term treatment with H(+)-K(+)-adenotriphosphatase
      (ATPase) inhibitors, such as omeprazole or lansoprazole, for severe
      gastroesophageal reflux disease is now widely used. Whether such treatment will
      result in vitamin B12 deficiency is controversial. We studied whether long-term
      treatment with omeprazole alters serum vitamin B12 levels in patients with
      Zollinger-Ellison syndrome. METHODS: In 131 consecutive patients treated with
      either omeprazole (n = 111) or histamine H2-receptor antagonists (n = 20), serum
      vitamin B12 and folate levels and complete blood counts were determined after
      acid secretion had been controlled for at least 6 months. These studies were
      repeated yearly. Serum vitamin B12 and folate levels were correlated with the
      type of antisecretory drug and the extent of inhibition of acid secretion.
      RESULTS: The mean duration of omeprazole treatment was 4.5 years, and for H2
      receptor antagonists 10 years. Vitamin B12 levels, but not serum folate levels or
      any hematological parameter, were significantly (P = 0.03) lower in patients
      treated with omeprazole, especially those with omeprazole-induced sustained
      hyposecretion (P = 0.0014) or complete achlorhydria (P < 0.0001). In 68 patients
      with two determinations at least 5 years apart, vitamin B12 levels decreased
      significantly (30%; P = 0.001) only in patients rendered achlorhydric. The
      duration of omeprazole treatment was inversely correlated with vitamin B12 levels
      (P = 0.013), but not folate levels. Eight patients (6%) developed subnormal B12
      levels during follow-up. CONCLUSIONS: Long-term omeprazole treatment leads to
      significant decreases in serum vitamin B12 but not folate levels. These results
      suggest patients with Zollinger-Ellison syndrome treated with H(+)-K(+)-ATPase
      inhibitors should have serum vitamin B12 levels monitored. Furthermore, these
      results raise the possibility that other patients treated chronically with H(+)
      K(+)-ATPase inhibitors may develop B12 deficiency.

PMID- 9626025
TI  - Effects of treatment with formoterol on bronchoprotection against methacholine.
AB  - PURPOSE: In addition to their bronchodilatory effects, beta(2)-agonists protect
      against bronchoconstriction, such as that caused by methacholine challenge.
      However, tachyphylaxis to this beneficial effect develops after chronic use of
      beta(2)-agonists. We studied whether the frequency or dose of treatment with a
      long-acting beta(2)-agonist (formoterol) affects the degree of bronchoprotection
      afforded against methacholine challenge and to compare this with the effects of a
      short-acting beta(2)-agonist (terbutaline). PATIENTS AND METHODS: In a
      randomized, parallel group, double-blind study at two centers, patients with
      stable asthma of mild to moderate severity who were treated with inhaled
      corticosteroids were treated with formoterol 6 micrograms twice daily, 24
      micrograms twice daily, 12 micrograms once daily; terbutaline 500 micrograms four
      times daily; or placebo. Treatments were given by dry powder inhaler for a period
      of 2 weeks. Of the 72 patients who were enrolled, 67 completed the study.
      Methacholine challenge was performed to calculate the provocative dose that
      caused a 20% fall in forced expiratory volume in 1 second at baseline
      (unprotected) after an initial 1-week run-in without beta(2)-agonists, 1 hour
      after the first dose of study treatment, and again 1 hour after 7 and 14 days of
      study treatment. RESULTS: Each of the four active treatments exhibited
      significant tachyphylaxis (P < 0.05) to protection against methacholine challenge
      when comparing first/last dose (as geometric mean protection ratio versus
      baseline): formoterol 24 micrograms twice daily (9.6-fold/1.6-fold), 12
      micrograms once daily (7.1-fold/2.2-fold), 6 micrograms twice daily (6.2-fold/2.3
      fold), and terbutaline 500 micrograms four times daily (2.9-fold/2.0-fold). There
      were no significant differences among treatments after 2 weeks in
      bronchoprotection against methacholine challenge. For all formoterol regimens,
      the bronchodilator response 1 hour after inhalation was maintained over the 2
      week treatment period. Diurnal control of morning and evening peak flow was
      significantly better with formoterol 24 micrograms twice daily than with
      terbutaline. CONCLUSIONS: Tachyphylaxis to bronchoprotection against methacholine
      challenge develops after 2 weeks of therapy with formoterol, a long-acting
      beta(2)-agonist, at all three dosage regimens that were tested. In contrast, the
      bronchodilator effects of formoterol were maintained during the 2 weeks of
      treatment.

PMID- 9626026
TI  - Racial differences in the prevalence of monoclonal gammopathy in a community
      based sample of the elderly.
AB  - PURPOSE: To determine if there is an increased prevalence of monoclonal
      gammopathy in elderly blacks compared with whites, analogous to the difference in
      incidence of multiple myeloma reported for the two racial groups and to confirm
      age and gender relationships. PATIENTS AND METHODS: Subjects were from the Duke
      Established Populations for the Epidemiologic Study of the Elderly, selected on
      the basis of stratified random household sampling. Blacks were oversampled to
      allow for increased statistical precision in racial comparisons. In all, 1,732
      subjects (aged > 70 years) consented to blood drawing and constitute the sample
      for this study. Monoclonal immunoglobulins were determined by agarose gel
      electrophoresis and immunofixation. RESULTS: One hundred six subjects (6.1%) had
      a monoclonal gammopathy. There was a greater than twofold difference in
      prevalence between blacks (8.4%) and whites (3.8%) (P < 0.001); monoclonal
      gammopathy prevalence increased with age, and was greater in men than women.
      Those with monoclonal gammopathy did not differ from those without in
      socioeconomic status, urban/rural residence, or education. The presence of
      monoclonal gammopathy was not associated with any specific diseases nor with
      impaired functional status. There was a slight increase in serum creatinine
      levels and decrease in hemoglobin and albumin levels in patients with monoclonal
      gammopathy, but no difference in interleukin-6 (IL-6) levels. Moreover, IL-6
      levels were not correlated significantly with the level of monoclonal protein.
      CONCLUSION: Prevalence of monoclonal gammopathy is significantly greater among
      blacks than whites in a community-based sample, in approximately the same ratio
      that multiple myeloma has been reported in the two groups. Given the absence of
      correlation with environmental factors, there may be a biological racial
      difference in susceptibility to an early event in the carcinogenic process
      leading to multiple myeloma.

PMID- 9626027
TI  - Remnant-like particle cholesterol levels in patients with dysbetalipoproteinemia
      or coronary artery disease.
AB  - PURPOSE: Several studies have provided support for a proatherogenic role for
      remnant lipoproteins. Thus, the aim of this study was to compare remnant-like
      particle (RLP) cholesterol levels in patients with coronary artery disease who
      were normolipidemic with those in controls of similar age and gender. We also
      assessed the usefulness of measuring RLP-cholesterol levels in patients with type
      III dyslipidemia. SUBJECTS AND METHODS: Remnant-like particle cholesterol levels
      were measured in 63 normolipidemic men with coronary artery disease and 23 male
      controls of similar age as well as in 15 patients with type III dyslipidemia and
      103 controls, using an immunoaffinity method. RESULTS: Remnant-like particle
      cholesterol levels were significantly increased in men with coronary artery
      disease compared with controls (7.6 +/- 3.8 mg/dL versus 5.7 +/- 1.9 mg/dL, P <
      0.01). In patients with coronary artery disease, RLP-cholesterol levels were
      correlated with total triglyceride and nonhigh-density-lipoprotein (HDL)
      cholesterol levels, but not with HDL-cholesterol levels. RLP-cholesterol levels
      were significantly elevated in patients with type III dyslipidemia (median 119,
      range 31 to 240 mg/dL) compared with controls (median 5.6, range 2.2 to 10.5
      mg/dL, P < 0.001). CONCLUSION: Normolipidemic men with coronary artery disease
      have increased levels of RLP-cholesterol that is not detected with conventional
      lipid screening. The RLP-cholesterol assay is a simple method for detecting high
      concentrations of remnant lipoproteins in patients with type III dyslipidemia.

PMID- 9626028
TI  - Blood thrombopoietin levels in clonal thrombocytosis and reactive thrombocytosis.
AB  - BACKGROUND: Although the distinction between clonal and reactive thrombocytosis
      is clinically relevant because clonal thrombocytosis has more thrombohemorragic
      complications, the differential diagnosis of these two entities can be difficult.
      Methods such as the detection of unstimulated erythroid or megakaryocyte colony
      growth are not readily available. Therefore, we measured blood thrombopoietin
      levels to determine whether these levels can be used to distinguish the two
      conditions. PATIENTS AND METHODS: Thrombopoietin levels were measured in 73
      patients with thrombocytosis (platelet count > 500,000/microL), including 39
      patients with clonal thrombocytosis (20 patients with essential thrombocythemia,
      15 with agnogenic myeloid metaplasia, 1 patient with polycythemia vera, and 3
      with undefined myeloproliferative disorders) and 34 patients with reactive
      thrombocytosis (17 with malignant tumors, 11 with inflammatory diseases, 4 with
      sickle cell disease, and 2 with iron deficiency anemia). Seventeen normal
      volunteers were used as controls. RESULTS: Thrombopoietin levels were
      significantly higher (P < 0.05) in patients with clonal thrombocytosis (mean +/-
      SD of 555 +/- 585 pg/mL), including the subgroup with essential thrombocythemia
      (505 +/- 459 pg/mL), than in patients with reactive thrombocytosis (290 +/- 133
      pg/mL) who had similar levels as controls (201 +/- 112 pg/mL). Thrombopoietin
      levels in patients with clonal thrombocytosis, including essential
      thrombocythemia, were not correlated with platelet counts. CONCLUSIONS:
      Thrombopoietin levels may be helpful in distinguishing between clonal
      thrombocytosis and reactive thrombocytosis. Thrombopoietin is probably
      responsible for the elevated platelet counts in clonal thrombocytosis including
      essential thrombocythemia, but not in reactive thrombocytosis. High
      thrombopoietin levels in patients with clonal thrombocytosis cannot be explained
      solely by platelet megakaryocyte mass.

PMID- 9626029
TI  - A pilot study of smokeless tobacco in smoking cessation.
AB  - PURPOSE: The substitution of smokeless tobacco for cigarette smoking is a harm
      reduction alternative for inveterate smokers and reduces others' passive exposure
      to smoke. Two million smokers have used smokeless tobacco to quit on their own,
      but no formal program has employed this method of smoking cessation. We conducted
      a pilot study to determine if smokeless tobacco could be successfully employed in
      a smoking cessation program. PATIENTS AND METHODS: Subjects attended a lecture
      about the health effects of all forms of tobacco use and about the use of
      smokeless tobacco as an aid to quit smoking. The study population consisted of 63
      evaluable subjects. Follow-up was accomplished by quarterly telephone interviews.
      Smoking abstinence was confirmed at 1 year by measurement of expired air carbon
      monoxide. RESULTS: At 1 year, 31% of men and 19% of women had attained smoking
      cessation, for an overall success rate of 25%. An additional 7% of subjects had
      reduced their cigarette consumption by at least 50%. CONCLUSION: This study
      suggests that the use of smokeless tobacco warrants evaluation as a potential
      smoking cessation strategy.

PMID- 9626030
TI  - Osteoporosis after organ transplantation.
AB  - Within the past 2 decades, organ transplantation has become established as
      effective therapy for endstage renal, hepatic, cardiac, and pulmonary disease.
      Regimens to prevent rejection after transplantation commonly include high-dose
      glucocorticoids and calcineurin-calmodulin phosphatase inhibitors (the
      cyclosporines and tacrolimus), which are detrimental to bone and mineral
      homeostasis, and are associated with rapid bone loss that is often superimposed
      upon an already compromised skeleton. The incidence of fracture ranges from 8% to
      65% during the first year after transplantation. In general, fracture rates are
      lowest in renal transplant recipients and highest in patients who receive a liver
      transplant for primary biliary cirrhosis. Rates of bone loss and fracture are
      greatest during the first 6 to 12 months after transplantation. Postmenopausal
      women and hypogonadal men appear to be at increased risk. Although no
      pretransplant densitometric or biochemical parameter has yet been identified that
      adequately predicts fracture risk in the individual patient, low pretransplant
      bone mineral density does tend to increase the risk of fracture, particularly in
      women. However, patients may sustain fractures despite normal pretransplant bone
      mineral density. Although the pathogenesis of the rapid bone loss is
      multifactorial, prospective biochemical data suggest that uncoupling of bone
      formation from resorption may be in part responsible, at least during the first 3
      to 6 months. Prevention of transplantation osteoporosis should begin well before
      transplantation. Patients awaiting transplantation should be evaluated with spine
      radiographs, bone densitometry, thyroid function tests, serum calcium, vitamin D,
      parathyroid hormone, and testosterone (in men). Therapy for osteoporosis, low
      bone mass, and potentially reversible biochemical causes of bone loss should be
      instituted during the waiting period before transplantation. In patients with
      normal pretransplant bone density, therapy to prevent early posttransplant bone
      loss should be instituted immediately following transplantation. Most
      pharmacologic agents available for therapy of osteoporosis have not been subject
      to prospective controlled studies in organ transplant recipients. However,
      antiresorptive drugs, such as biphosphonates, appear to hold therapeutic promise.

PMID- 9626031
TI  - Malignant hyperthermia and central core disease: disorders of Ca2+ release
      channels.

PMID- 9626032
TI  - The abrupt onset of Graves' disease: documentation in the setting of a controlled
      feeding study.

PMID- 9626033
TI  - Quinine hypersensitivity simulating sepsis.

PMID- 9626034
TI  - Metformin-induced acute hepatitis.

PMID- 9626035
TI  - Long-acting inhaled beta 2-agonists and the loss of "bronchoprotective" efficacy.

PMID- 9626036
TI  - Yet another smoke(less) screen?

PMID- 9626037
TI  - Treating cigarette smoking with smokeless tobacco: a flawed recommendation.

PMID- 9626038
TI  - Can smokeless tobacco rid us of tobacco smoke?

PMID- 9626039
TI  - Hyponatremic encephalopathy.

PMID- 9626040
TI  - Long-term survival in Waldenstrom's macroglobulinemia.

PMID- 9626041
TI  - Hyperparathyroidism in congestive heart failure.

PMID- 9626042
TI  - Impact of echocardiography on antibiotic prophylaxis with suspected mitral valve
      prolapse.

PMID- 9626043
TI  - Dysregulated expression of CD66a (BGP, C-CAM), an adhesion molecule of the CEA
      family, in endometrial cancer.
AB  - CD66a (BGP, C-CAM) is an adhesion molecule of the carcinoembryonic antigen family
      that has been shown to be down-regulated in colorectal, prostate, and breast
      cancers. The purpose of the present study was to determine its expression pattern
      in the normal human endometrium and in endometrial neoplasia. For this purpose,
      we performed immunohistochemistry using the 4D1/C2 monoclonal antibody on a
      series of 24 normal endometrial samples and 47 endometrial carcinomas. Strong
      CD66a expression was observed in glandular and luminal epithelial cells of the
      normal endometrium with a consistent localization at the apical poles of these
      cells throughout the cycle. In late secretory (premenstrual) phase, loss of
      cellular polarity resulted in a membranous expression pattern in some glandular
      cells. In the analyzed tumor samples increasing areas with a complete loss of
      expression were observed with increasing malignancy grade. The apical expression
      pattern of the normal epithelium was changed to a membranous all-around pattern
      in 55% of the tumors, mostly in solid areas. This change correlated with
      malignancy grade and could be observed in 3 of 15 G1 tumors, 4 of 12 G2 tumors,
      11 of 12 G3 tumors, and 8 of 8 serous-papillary carcinomas. Areas with membranous
      expression pattern could be observed along with areas with a normal apical
      expression pattern in lower grade carcinomas and with areas with complete loss of
      expression in high grade tumors. Northern blot analysis showed a loss of mRNA
      expression in tumor samples and HEC-1B endometrial adenocarcinoma cells. Loss of
      protein expression in the tumor samples was also observed by Western blot. In
      conclusion, CD66a protein expression is dysregulated in endometrial carcinomas,
      showing reduction or loss of expression with increasing malignancy grade and a
      change from the apical to a membranous localization.

PMID- 9626044
TI  - Bcl-2 and c-Myc, but not bax and p53, are expressed during human medullary
      thyroid tumorigenesis.
AB  - Medullary thyroid carcinoma (MTC) is a tumor of parafollicular cells of the
      thyroid gland. It has served as a useful experimental model for the study of
      tumor proliferation and differentiation. Although recent studies have identified
      the gene involved in familial forms of MTC, little is known about the molecular
      pathogenesis of the sporadic variants of this tumor. It has become increasingly
      clear that deregulation of programmed cell death is a critical component in
      multistep tumorigenesis. The present investigation was undertaken to determine
      whether similar molecular events occur in human MTC. Eighteen MTCs from 18
      patients (including 12 sporadic and six familial cases and one metastatic lymph
      gland) and a MTC cell line (TT cells) were used in this study for detecting the
      expression of apoptosis-regulatory genes bcl-2, bax, c-myc, and p53.
      Immunohistochemical results showed that all MTC tumor samples displayed Bcl-2 and
      c-Myc immunoreactivity, whereas only 4 and 2 tumors showed a minority of cells
      positive for Bax and p53, respectively. Western and Northern blotting showed high
      levels of 26-kd Bcl-2 protein and bcl-2 transcript. The co-expression of Bcl-2
      and c-Myc was also detected in the TT cells by indirect fluorescence
      immunohistochemistry and Western blotting. Moreover, Bcl-2 immunoreactivity was
      also found in C-cell hyperplasia from familial patients indicating that
      expression of this oncogene may represent an early event in the pathogenesis of
      MTC. The present study suggests that deregulation of programmed cell death may be
      a critical component in multistep tumorigenesis of MTC and that the frequent
      expression of the Bcl-2 oncoprotein in these tumors may contribute to their
      pathogenesis. The genetic complementation of simultaneously deregulated bcl-2 and
      c-myc may be implicated in the multistep tumorigenesis of human MTC.

PMID- 9626045
TI  - An antibody raised against a conserved sequence of the prion protein recognizes
      pathological isoforms in human and animal prion diseases, including Creutzfeldt
      Jakob disease and bovine spongiform encephalopathy.
AB  - Antibodies to the prion protein (PrP) have been critical to the neuropathological
      and biochemical characterization of PrP-related degenerative diseases in humans
      and animals. Although PrP is highly conserved evolutionarily, there is some
      sequence divergence among species; as a consequence, anti-PrP antibodies have a
      wide spectrum of reactivity (from strong immunopositivity to lack of reactivity)
      when challenged with PrP from diverse species. We have produced an antibody (anti
      PrP95-108) raised against a synthetic peptide corresponding to residues 95 to 108
      of human PrP and have characterized it by epitope mapping, Western immunoblot
      analysis, and immunohistochemistry. The antibody recognizes not only human PrP
      isoforms but also pathological PrP from all species tested (ie, cattle, sheep,
      hamsters, and mice). This is probably due to the fact that the epitope recognized
      by this antibody includes residues 100 to 108 of human PrP, a sequence that is
      also present in PrP of several other species. Thus, this reagent is valuable not
      only for the study of human prion diseases but also for analysis of the possible
      relationship between human and animal disorders.

PMID- 9626046
TI  - New monoclonal antibodies to the T cell antigens CD4 and CD8. Production and
      characterization in formalin-fixed paraffin-embedded tissue.
AB  - We have generated a recombinant protein representing part of the CD4 molecule and
      a peptide representing an epitope of predicted high antigenicity on the CD8
      molecule and employed these to generate mouse monoclonal antibodies using
      standard hybridoma protocols. The extracellular domain of the CD4 molecule was
      obtained by reverse transcription of mRNA from peripheral blood lymphocytes
      followed by polymerase chain reaction. The amplified gene fragment was cloned
      into an expression vector to allow a histidine-tagged fusion protein to be
      produced in Escherichia coli. Purified fusion protein was used to immunize mice.
      The CD8 monoclonal antibody was raised against a peptide consisting of 13 amino
      acids within the carboxyl-terminal region of the CD8 cytoplasmic domain. The
      antibodies showed appropriate reactivity on Western blotting. By heat
      pretreatment, these antibodies have been shown to be highly effective on paraffin
      embedded tissue. In normal lymphoid tissue, the expected distribution of CD4 and
      CD8 lymphocytes was observed. In a series of 16 T cell lymphomas and B cell
      lymphomas, immunostaining results were compared with those obtained using
      reagents effective only in frozen tissue. A high degree of correlation was
      observed. These results suggest that NCL-CD4 and NCL-CD8 may be of value in the
      characterization of T cell disorders.

PMID- 9626047
TI  - Cellular immuno-PCR. Detection of a carbohydrate tumor marker.
AB  - Carbohydrate tumor-antigens are important tumor markers for diagnosis and
      functional characteristics of human cancer cells. Detection of these carbohydrate
      tumor antigens on metastatic cancer cells in blood is a difficult task. We
      developed a highly sensitive method to detect a cell surface carbohydrate antigen
      using a hybrid technology referred to as cellular immuno-PCR. This technique uses
      the human monoclonal antibody (HumAb) L612, specific to a tumor-related antigen
      (ganglioside) GM3 that is expressed on the cell surface of human tumor cells and
      not normal cells. L612 coupled to a DNA oligonucleotide for exponential
      amplification by DNA polymerase chain reaction (PCR) can be used to enhance the
      detection signal. The DNA-HumAb conjugate was assessed for detection of a small
      number of human cancer cells after PCR amplification and Southern blot analysis.
      To assess the assay specificity human melanoma and other cancer cell lines, as
      well as healthy donor and melanoma patients, bloods were assessed. Cellular
      immuno-PCR requires < 1 ng/ml DNA-HumAb complex and was shown to have a detection
      level of < 10 cells in titration studies in which melanoma cells were diluted in
      2 million healthy donor peripheral blood lymphocytes. The assay was shown to be
      very sensitive and could detect low levels of GM3 antigen expression by tumor
      cells. This novel approach for detecting a carbohydrate tumor antigen on tumor
      cells in blood provides a potential useful clinicopathological assay.

PMID- 9626048
TI  - Vascular endothelial growth factor and basic fibroblast growth factor present in
      Kaposi's sarcoma (KS) are induced by inflammatory cytokines and synergize to
      promote vascular permeability and KS lesion development.
AB  - All forms of Kaposi's sarcoma (KS) are characterized by spindle cell
      proliferation, angiogenesis, inflammatory cell infiltration, and edema. We have
      previously reported that spindle cells of primary KS lesions and KS-derived
      spindle cell cultures express high levels of basic fibroblast growth factor
      (bFGF), which is promoted by the inflammatory cytokines identified in these
      lesions. These cytokines, namely, tumor necrosis factor, interleukin-1, and
      interferon-gamma, induce production and release of bFGF, which stimulates
      angiogenesis and spindle cell growth in an autocrine fashion. Here we show that
      both AIDS-KS and classical KS lesions co-express vascular endothelial growth
      factor (VEGF) and bFGF. VEGF production by KS cells is promoted synergistically
      by inflammatory cytokines present in conditioned media from activated T cells and
      in KS lesions. KS cells show synthesis of VEGF isoforms that are mitogenic to
      endothelial cells but not to KS spindle cells, suggesting a prevailing paracrine
      effect of this cytokine. This may be due to the level of expression of the flt-1
      VEGF receptor that is down-regulated in KS cells as compared with endothelial
      cells. KS-derived bFGF and VEGF synergize in inducing endothelial cell growth as
      shown by studies using both neutralizing antibodies and antisense
      oligodeoxynucleotides directed against these cytokines. In addition, VEGF and
      bFGF synergize to induce angiogenic KS-like lesions in nude mice and vascular
      permeability and edema in guinea pigs. These results indicate that inflammatory
      cytokines present in KS lesions stimulate the production of bFGF and VEGF, which,
      in turn, cooperate to induce angiogenesis, edema, and KS lesion formation.

PMID- 9626049
TI  - Vascular endothelial growth factor mediates angiogenic activity during the
      proliferative phase of wound healing.
AB  - Angiogenesis is an essential component of normal wound repair, yet the primary
      mediators of wound angiogenesis have not been well described. The current study
      characterizes the contribution of vascular endothelial cell growth factor (VEGF)
      to the angiogenic environment of human surgical wounds. Surgical wound fluid
      samples (n = 70) were collected daily for up to 7 postoperative days (POD) from
      14 patients undergoing mastectomy or neck dissection. VEGF levels in surgical
      wound fluid were lowest on POD 0, approximating values of serum, but increased
      steadily through POD 7. An opposite pattern was noted for basic fibroblast growth
      factor-2. Fibroblast growth factor-2, which has been previously described as a
      wound angiogenic factor, exhibited highest levels at POD 0, declining to near
      serum levels by POD 3. Surgical wound fluid form all time points stimulated
      marked endothelial cell chemotaxis and induced a brisk neovascular response in
      the rat corneal micropocket angiogenesis assay. Antibody neutralization of VEGF
      did not affect the in vitro chemotactic or the in vivo angiogenic activity early
      wound samples (POD 0). In contrast, VEGF neutralization significantly attenuated
      both chemotactic activity (mean decrease 76 +/- 13%, P < 0.01) and angiogenic
      activity (5 of 5 samples affected) of later wound samples (POD 3 and 6). The
      results suggest a model of wound angiogenesis in which an initial angiogenic
      stimulus is supplied by fibroblast growth factor-2, followed by a subsequent and
      more prolonged angiogenic stimulus mediated by VEGF.

PMID- 9626050
TI  - Expression of vascular endothelial growth factor in the human retina and in
      nonproliferative diabetic retinopathy.
AB  - Vascular endothelial growth factor (VEGF)/vascular permeability factor is a
      likely angiogenic mediator in proliferative diabetic retinopathy, and its role is
      under scrutiny in the pathogenesis of the capillary leakage characteristic of
      background diabetic retinopathy. To examine whether the diabetic milieu induces
      or increases retinal VEGF expression in humans, we examined retinas from
      nondiabetic eye donors and donors with 9 +/- 5 years of diabetes and documented
      microangiopathy. To identify possible confounding effects of the postmortem
      period, we also studied the postmortem stability of the VEGF transcript and the
      expression of the VEGF protein in rat retinas. In both human and rat retina we
      detected by Northern analysis a 4.2-kb VEGF mRNA species and by reverse
      transcriptase polymerase chain reaction the transcripts encoding VEGF165 (the
      most abundant), VEGF121, and VEGF189. By in situ hybridization and
      immunohistochemistry VEGF mRNA and protein co-localized at the ganglion cell,
      inner nuclear, and outer plexiform layers and in the walls of the blood vessels
      (where mRNA was scarce). The protein was additionally detected in photoreceptors.
      The abundance and distribution of VEGF mRNA and protein were not altered in the
      diabetic retinas, indicating that the diabetic environment is not sufficient to
      increase retinal VEGF expression. The demonstration that VEGF is constitutively
      expressed in the adult retina and is localized to discrete neural cells and their
      processes proposes a role for the cytokine in retinal homeostasis and/or
      function.

PMID- 9626051
TI  - Endothelial gaps and adherent leukocytes in allergen-induced early- and late
      phase plasma leakage in rat airways.
AB  - Exposure of sensitized individuals to antigen can induce allergic responses in
      the respiratory tract, manifested by early and late phases of vasodilatation,
      plasma leakage, leukocyte influx, and bronchoconstriction. Similar responses can
      occur in the skin, eye, and gastrointestinal tract. The early-phase response
      involves mast cell mediators and the late-phase response is leukocyte dependent,
      but the mechanism of leakage is not understood. We sought to identify the leaky
      blood vessels, to determine whether these vessels contained endothelial gaps, and
      to analyze the relationship of the gaps to adherent leukocytes, using
      biotinylated lectins or silver nitrate to stain the cells in situ and Monastral
      blue as a tracer to quantify plasma leakage. Most of the leakage occurred in
      postcapillary venules (< 40-microns diameter), whereas most of the leukocyte
      migration (predominantly neutrophils) occurred in collecting venules. Capillaries
      and arterioles did not leak. Endothelial gaps were found in the leaky venules,
      both by silver nitrate staining and by scanning electron microscopy, and 94% of
      the gaps were distinct from sites of leukocyte adhesion or migration. We conclude
      that endothelial gaps contribute to both early and late phases of plasma leakage
      induced by antigen, but most leakage occurs upstream to sites of leukocyte
      adhesion.

PMID- 9626052
TI  - Systemic endothelial activation occurs in both mild and severe malaria.
      Correlating dermal microvascular endothelial cell phenotype and soluble cell
      adhesion molecules with disease severity.
AB  - Fatal Plasmodium falciparum malaria is accompanied by systemic endothelial
      activation. To study endothelial activation directly during malaria and sepsis in
      vivo, the expression of cell adhesion molecules on dermal microvascular
      endothelium was examined in skin biopsies and correlated with plasma levels of
      soluble (circulating) ICAM-1, E-selectin, and VCAM-1 and the cytokine tumor
      necrosis factor (TNF)-alpha. Skin biopsies were obtained from 61 cases of severe
      malaria, 42 cases of uncomplicated malaria, 10 cases of severe systemic sepsis,
      and 17 uninfected controls. Systemic endothelial activation, represented by the
      up-regulation of inducible cell adhesion molecules (CAMs) on endothelium and
      increased levels of soluble CAMs (sCAMs), were seen in both severe and
      uncomplicated malaria and sepsis when compared with uninfected controls. Plasma
      levels of sICAM-1, sVCAM-1, and sE-selectin correlated positively with the
      severity of malaria whereas TNF-alpha was raised nonspecifically in malaria and
      sepsis. Immunohistochemical evidence of endothelial activation in skin biopsies
      did not correlate with sCAM levels or disease severity. This indicates a
      background of systemic endothelial activation, which occurs in both mild and
      severe malaria and sepsis. The levels of sCAMs in malaria are thus not an
      accurate reflection of endothelial cell expression of CAMs in a particular
      vascular bed, and other factors must influence their levels during disease.

PMID- 9626054
TI  - Pancreatic adenocarcinomas with DNA replication errors (RER+) are associated with
      wild-type K-ras and characteristic histopathology. Poor differentiation, a
      syncytial growth pattern, and pushing borders suggest RER+.
AB  - The clinical and pathological features of carcinomas of the pancreas with DNA
      replication errors (RER+) have not been characterized. Eighty-two xenografted
      carcinomas of the pancreas were screened for DNA replication errors using
      polymerase chain reaction amplification of microsatellite markers. Cases with
      microsatellite instability in at least two markers of a minimum of five tested
      were considered RER+. RER status was correlated with histological appearance,
      karyotype of the carcinomas when available, K-ras mutational status, and patient
      outcome. Three (3.7%) of the eighty-two carcinomas were RER+. In contrast to
      typical gland-forming adenocarcinomas of the pancreas, all three RER+ carcinomas
      were poorly differentiated and had expanding borders and a prominent syncytial
      growth pattern. Neither a Crohn's-like lymphoid infiltrate nor extracellular
      mucin production were prominent. Ductal adenocarcinomas of the pancreas typically
      contain a mutant K-ras gene, yet all three RER+ carcinomas had wild-type K-ras.
      One of the three RER+ carcinomas was karyotyped and showed a near diploid
      pattern. All three of the RER+ tumors were removed via Whipple resection. One of
      the three patients is free of disease 16 months after pancreaticoduodenectomy,
      one is alive and free of tumor at 52 months but developed two colon carcinomas
      during this period, and the third died of pancreatic cancer at 4 months. None of
      the three patients had a family history of colorectal carcinoma. A review of the
      K-ras wild-type carcinomas in a previously characterized series of pancreatic
      carcinomas with known K-ras mutational status identified two additional cancers
      with poor differentiation, a syncytial growth pattern, and pushing borders. Both
      of the cancers were diploid and both patients were longterm survivors (over 5
      years). The inclusion of such patients in previous prognostic studies of pancreas
      cancer may explain the failure of histological grade to be a predictor of
      prognosis. These data suggest that DNA replication errors occur in a small
      percentage of resected carcinomas of the pancreas and that wild-type K-ras gene
      status and a medullary phenotype characterized by poor differentiation, and
      expanding pattern of invasion, and syncytial growth should suggest the
      possibility of DNA replication errors in carcinomas of the pancreas.

PMID- 9626053
TI  - Collagenase-3 (matrix metalloproteinase-13) expression is induced in oral mucosal
      epithelium during chronic inflammation.
AB  - Increased proliferation of mucosal epithelium during inflammation is associated
      with degradation of subepithelial connective tissue matrix and local invasion of
      the epithelial cells. Here we have studied, whether collagenase-3 (MMP-13), a
      collagenolytic matrix metalloproteinase with an exceptionally wide substrate
      specificity, is expressed in the epithelium of chronically inflamed mucosa.
      Examination of human gingival tissue sections from subjects with chronic adult
      periodontitis with in situ hybridization revealed marked expression of MMP-13 in
      basal cells of some epithelial rete ridges expanding into connective tissue.
      Immunohistochemical staining demonstrated that these cells also expressed
      strongly laminin-5, suggesting that they are actively migrating cells. A strong
      signal for MMP-13 mRNA was occasionally also noted in the suprabasal epithelial
      cells facing the gingival pocket, whereas no collagenase-1 (MMP-1) mRNA was
      detected in any areas of the epithelium. MMP-13 expression was also detected in
      fibroblast-like cells associated with collagen fibers of the inflamed
      subepithelial connective tissue. In organ culture of human oral mucosa, MMP-13
      mRNA expression was observed in epithelial cells growing into connective tissue
      of the specimens. Regulation of MMP-13 expression was examined in cultured normal
      nonkeratinizing epithelial cells isolated from porcine periodontal ligament. In
      these cells, MMP-13 expression at the mRNA and protein level was potently
      enhanced (up to sixfold) by tumor necrosis factor-alpha, transforming growth
      factor-beta(1), and transforming growth factor-alpha and by keratinocyte growth
      factor in the presence of heparin. In addition, plating periodontal ligament
      epithelial cells on type I collagen stimulated MMP-13 expression (sevenfold) as
      compared with cells grown on tissue culture plastic. The results of this study
      show, that expression of MMP-13 is specifically induced in undifferentiated
      epithelial cells during chronic inflammation due to exposure to cytokines and
      collagen. Thus, it is likely that MMP-13 expression is instrumental in the
      subepithelial collagenolysis and local invasion of the activated mucosal
      epithelium into the connective tissue.

PMID- 9626055
TI  - Studies on the pathology, especially brain lesions, induced by R7, a spontaneous
      mutant of Moloney murine sarcoma virus 124.
AB  - We have recently isolated R7, a spontaneous Moloney murine sarcoma virus (MoMuSV)
      124 variant. Molecular cloning and sequence analysis showed that, relative to
      MoMuSV 124, R7 has an extra repeat in each enhancer and a truncated mos gene in
      frame with the truncated gag coding sequence. This report presents a detailed
      study on the pathology induced by R7. R7 induced not only sarcomas with well
      developed angiomatous components but also brain lesions. Brain lesions were
      observed in all less-than-48-hour-old BALB/c mice inoculated with greater than 2
      x 10(5) R7 focus-forming units (FFUs). R7 was detected in all brains examined by
      day 9 after inoculation, and brain lesions were observed in two of four mice
      examined by day 14 after inoculation. Light microscopy of brains revealed that
      approximately 15% of the lesions were unenclosed blood pools of varying sizes
      containing red blood cells and inflammatory cells spreading into surrounding
      brain tissues. The remainder of the brain lesions had tumor cells. These lesions
      ranged from a few enlarged vascular endothelial cells intermixed with blood cells
      to large circumscribed lesions consisting of well developed tangled masses of
      vessels surrounded by blood pools. Activated astrocytes surrounded and
      infiltrated the tumors. In addition, the thymus of R7-infected mice regressed
      significantly and precipitously due to apoptosis (especially of cortical
      thymocytes) at the end stage of the disease.

PMID- 9626056
TI  - Transduction of human trophoblastic cells by replication-deficient recombinant
      viral vectors. Promoting cellular differentiation affects virus entry.
AB  - We investigated the transfer of the lacZ reporter gene into human trophoblastic
      cells using herpes simplex virus and adeno-associated virus vectors. We used an
      established choriocarcinoma cell line (BeWo cells) that can be induced to
      terminally differentiate after treatment with cyclic-AMP. Our results demonstrate
      that transduction of trophoblastic cells by the herpes simplex virus vector,
      HSV.CMVlac, and the adeno-associated virus vector, AAV.CMVlac, is affected by
      cellular differentiation. Treatment of BeWo cells with cyclic-AMP reduced
      transduction by HSV.CMVlac but increased transduction by the AAV vector. In
      contrast, when BeWo cells were transfected with herpes simplex virus and adeno
      associated virus plasmids, lacZ expression was not affected by treatment with
      cyclic-AMP. Southern blot analysis demonstrated 2.75 times less herpes simplex
      virus DNA in cyclic-AMP treated BeWo cells, but 2.0 to 7.4 times more adeno
      associated virus DNA in treated cells. We conclude that inefficient transduction
      of differentiated trophoblastic cells with HSV.CMVlac is because of diminished
      viral entry, whereas cellular differentiation is associated with increased entry
      of AAV.CMVlac. These observations suggest that adeno-associated virus vectors may
      be used to modify trophoblast function and study placental physiology.
      Additionally, trophoblast differentiation leads to alterations in the mechanisms
      of virus uptake that may affect maternal-to-fetus transmission.

PMID- 9626057
TI  - Ferritin is associated with the aberrant tau filaments present in progressive
      supranuclear palsy.
AB  - Tau-containing filaments purified from the brain of progressive supranuclear
      palsy (PSP) patients were isolated and characterized. These filaments co-purify
      with regular particles that biophysical and biochemical methods identified as
      ferritin shells. In vivo, brain tau accumulation in PSP co-localized with
      ferritin. These results suggest that ferritin/iron could modulate the formation
      of tau aggregates in PSP.

PMID- 9626058
TI  - Crescentic glomerulonephritis in CD4- and CD8-deficient mice. Requirement for CD4
      but not CD8 cells.
AB  - The contribution of CD4 and CD8 cells to crescentic glomerulonephritis (GN) was
      studied in mice genetically deficient in CD4, CD8, and with combined CD4 and CD8
      (CD4/CD8) deficiency. Wild-type (C57BL/6) mice developed GN with mild
      proliferative changes 7 days after an intravenous dose of sheep anti-mouse
      glomerular basement membrane globulin. Crescents were observed in 12.5 +/- 6.1%
      of glomeruli on day 14. On day 21, 51.5 +/- 7.3% of glomeruli were affected by
      crescents, and mice had marked azotemia and proteinuria. CD4 and combined CD4/CD8
      deficient mice developed minimal evidence of GN. On day 21, their glomeruli
      showed only mild proliferative changes and crescents, azotemia, and proteinuria
      were absent. In contrast, CD8-deficient mice developed severe crescentic GN with
      three of five mice dying on day 20 with ascites and edema. The two mice surviving
      to day 21 had severe azotemia. Crescent development was accelerated (day 14, 51.6
      +/- 2.4% of glomeruli; day 20 or 21, 62.0 +/- 4.0% of glomeruli). These studies
      demonstrate that CD4 cells are crucial for the development of crescentic GN in
      mice and that genetic absence of CD8 cells accelerates disease. They support the
      hypothesis that crescent formation is a manifestation of CD4-dependent (and CD8
      independent) delayed type hypersensitivity in the glomerulus.

PMID- 9626059
TI  - TRAF-4 expression in epithelial progenitor cells. Analysis in normal adult,
      fetal, and tumor tissues.
AB  - TRAF-4 was discovered because of its expression in breast cancers and is a member
      of the tumor necrosis factor (TNF) receptor-associated factor (TRAF) family of
      putative signal-transducing proteins. In vitro binding assays demonstrated that
      TRAF-4 interacts with the cytosolic domain of the lymphotoxin-beta receptor (LT
      beta R) and weakly with the p75 nerve growth factor receptor (NGFR) but not with
      TNFR1, TNFR2, Fas, or CD40. Immunofluorescence analysis of TRAF-4 in transfected
      cells demonstrated localization to cytosol but not nucleus. Immunohistochemical
      assays of normal human adult tissues revealed prominent cytosolic immunostaining
      in thymic epithelial cells and lymph node dendritic cells but not in lymphocytes
      or thymocytes, paralleling the reported patterns of LT beta R expression. The
      basal cell layer of most epithelia in the body was very strongly TRAF-4
      immunopositive, including epidermis, nasopharynx, respiratory tract, salivary
      gland, and esophagus. Similar findings were obtained in 12- to 18-week human
      fetal tissue, indicating a highly restricted pattern of expression even during
      development in the mammary gland, epithelial cells of the terminal ducts were
      strongly TRAF-4 immunopositive whereas myoepithelial cells and most of the
      mammary epithelial cells lining the extralobular ducts were TRAF-4
      immunonegative. Of 84 primary breast cancers evaluated, only 7 expressed TRAF-4.
      Ductal carcinoma in situ (DCIS) lesions were uniformly TRAF-4 immunonegative (n =
      21). In the prostate, the basal cells were strongly immunostained for TRAF-4,
      whereas the secretory epithelial cells were TRAF-4 negative. Basal cells in
      prostate hypertrophy (n = 6) and prostatic intraepithelial neoplasia (PIN; n = 6)
      were strongly TRAF-4 positive, but none of the 32 primary and 16 metastatic
      prostate cancer specimens examined contained TRAF-4-positive malignant cells.
      Although also expressed in some types of mesenchymal cells, these findings
      suggest that TRAF-4 is a marker of normal epithelial stem cells, the expression
      of which often ceases on differentiation and malignant transformation.

PMID- 9626060
TI  - novH: differential expression in developing kidney and Wilm's tumors.
AB  - We previously established that the expression of the human nov gene (novH) was
      altered in Wilms' tumors and that levels of novH and WT1 mRNA were inversely
      correlated in individual Wilms' tumors. Insofar as novH has been shown to be a
      target for WT1 regulation, novH might play an important role during normal
      nephrogenesis and in the development of Wilms' tumors. We now show that during
      normal nephrogenesis novH protein is tightly associated with differentiation of
      glomerular podocytes. NovH expression is not restricted to renal differentiation
      but is also detected in endothelium and neural tissue of the kidney. Our results
      establish that alteration of novH expression in sporadic and heritable Wilms'
      tumors is associated with dysregulated expression of both novH mRNA and protein.
      In general, the highest novH expression was noted in the Wilms' tumor,
      genitourinary anomalies, aniridia, and mental retardation (WAGR)-associated
      Wilms' tumors. Expression in the Denys-Drash syndrome (DDS)-associated Wilms'
      tumors fell within the variable spectrum observed in sporadic Wilms' tumor cases.
      As in developing kidney podocytes, novH protein was also prominent in the
      abnormal hypoplastic podocytes from DDS cases and in kidney podocytes adjoining
      Wilms' tumors. In Wilms' tumors exhibiting heterotypic differentiation, novH
      protein was expressed at high levels in tumor-derived striated muscle and at
      lower levels in tumor-derived cartilage. These observations taken together
      indicate that novH may represent both a marker of podocytic differentiation in
      kidney and a marker of heterotypic mesenchymal differentiation in Wilms' tumors.
      In addition, absence or very low levels of WT1 are correlated with higher novH
      expression, and its variable expression in cases with mutant WT1 (sporadic and
      DDS) suggests that the potential activation and repression transcriptional
      functions possessed by WT1 are likely dependent on the specific mutation
      incurred.

PMID- 9626061
TI  - Deficient liver regeneration after carbon tetrachloride injury in mice lacking
      type 1 but not type 2 tumor necrosis factor receptor.
AB  - Signaling by tumor necrosis factor type 1 receptor (TNFR-1) is required for the
      initiation of liver regeneration after partial hepatectomy. Using knockout mice
      that lack either TNFR-1 or TNFR-2, we determined whether signaling through TNF
      receptors is important for liver injury and hepatocyte proliferation induced by
      carbon tetrachloride (CCl4). Lack of TNFR-1 inhibited hepatocyte DNA synthesis
      after CCl4 injection. At 44 hours after the injection, replication of hepatocytes
      in TNFR-1 was 50% to 90% lower than in wild-type (WT) animals, depending on the
      dose injected. In WT animals, hepatocyte replication was essentially completed by
      4 days after CCl4 injection, but replication at a low level persisted in TNFR-1
      mice for at least 2 weeks. TNFR-1 knockout mice had little detectable NF-kappa B
      and STAT3 binding during the first 5 hours after CCl4, high plasma TNF, and
      reduced levels of plasma interleukin (IL)-6 and liver IL-6 mRNA. Injection of IL
      6 30 minutes before CCl4 administration corrected the deficiency of hepatocyte
      replication at 44 hours and restored STAT3 binding to normal levels. In contrast,
      mice lacking TNFR-2 did not differ significantly from WT mice in NF-kappa B and
      STAT3 binding, IL-6 and TNF levels, or hepatocyte replication. Although AP-1
      binding was induced in WT TNFR-1 and TNFR-2 knockout mice, binding in TNFR-2
      knockouts was lower than in WT mice. C/EBP binding was much lower in TNFR-1 and
      TNFR-2 knockout mice than in WT mice. As assessed by morphological analysis and
      alanine aminotransferase levels, the acute injury caused by CCl4 appeared to be
      similar in the three groups of animals, but subsequent regeneration was impaired
      in mice lacking TNFR-1. We conclude that a TNFR-1 signaling pathway involving NF
      kappa B, IL-6, and STAT3 is an important component of the hepatocyte mitogenic
      response induced by CCl4 injury in mouse liver.

PMID- 9626062
TI  - Genetically abnormal clones in histologically normal breast tissue.
AB  - Breast cancer is believed to develop as multiple genetic abnormalities
      accumulate, each conferring some growth advantage, but the timing and nature of
      the earliest steps in this progression are not yet elucidated. Proliferative
      breast lesions, associated with an increased risk of breast cancer although
      considered benign, recently were shown to contain clonal genetic abnormalities.
      Therefore, we hypothesized that clonal genetic abnormalities might be detectable
      before any phenotypic abnormalities are evident, ie, in histologically normal
      breast tissue. We examined DNA extracted from 95 normal-appearing breast ducts or
      terminal ductal-lobular units from 20 individuals at varying degrees of risk
      (those undergoing reduction mammoplasties, those with atypical hyperplastic
      proliferative lesions, and those already diagnosed with breast cancer). Using
      nine microsatellite markers, we sought evidence of genetic instability or of
      allelic imbalance (most likely representing loss of heterozygosity). We found
      genetically abnormal clones in 21/95 (22%) seemingly normal samples from 10/20
      (50%) women from all three risk groups. In women under age 50, trends toward
      increased rates of abnormalities were noted with increased cancer risk. The
      abnormalities identified were more likely to be at sites of known or postulated
      tumor suppressor genes rather than at random or neutral loci. Our data indicate
      that genetic abnormalities potentially critical to breast tumorigenesis
      accumulate before pathological detection even of high-risk lesions and are
      detectable in tissue that is not only histologically benign but also completely
      normal.

PMID- 9626063
TI  - Fibronectin modulates the effects of HIV-1 Tat on the growth of murine Kaposi's
      sarcoma-like cells through the down-regulation of tyrosine phosphorylation.
AB  - HIV-1 Tat plays a role in the pathogenesis of Kaposi's sarcoma. We therefore
      investigated the effect of Tat on the growth of murine Kaposi's sarcoma-like
      spindle (TTB) cells derived from dermal lesions. We observed that Tat and a
      peptide corresponding to the carboxyl-terminal region (Tat65-80) containing an
      RGD sequence inhibit TTB cell proliferation only when cells are cultured on
      fibronectin. This inhibitory effect correlates with redistribution of the
      alpha(v) integrin subunit on the surface of TTB cells and with down-regulation of
      tyrosine phosphorylation of specific substrates due to an increased tyrosine
      phosphatase activity. Indeed, phenylarsine oxide, a potent inhibitor of
      phosphotyrosine phosphatases, prevented the effects of Tat on TTB cells. We
      therefore argue that the action of Tat on TTB cells is mediated by the RGD motif
      through an integrin-based cell signaling pathway involving the activity of
      phosphotyrosine phosphatase(s), which would lead to a decrease in the levels of
      phosphotyrosine-containing proteins, among which is erk-2/p42MAPK.

PMID- 9626064
TI  - Impact of fibroblast growth factor-2 on tumor microvascular architecture. A
      tridimensional morphometric study.
AB  - Three cell clones originated by transfection of human endometrial adenocarcinoma
      HEC-1-B cells with fibroblast growth factor-2 (FGF-2) cDNA and characterized by a
      different capacity to produce and secrete the growth factor were transplanted
      subcutaneously in nude mice. Corrosion casting of the tumor microvasculature of
      xenografts produced by injection of 2 x 10(6) or 10 x 10(6) FGF-2-B9 cells (which
      produce and secrete significant amounts of FGF-2), 10 x 10(6) FGF-2-A8 cells
      (which produce comparable amounts of FGF-2 but do not secrete it), or 10 x 10(6)
      control FGF-2-B8 cells (which produce only trace amounts of FGF-2) was performed
      after 14 days of growth. Interbranching distances, intervascular distances,
      branching angles, and vessel diameters were then determined using tridimensional
      stereo pairs of the casted tumor vascularity. When transplanted at the same
      concentration, FGF-2-B9 cells grew faster in nude mice compared with FGF-2-A8 and
      FGF-2-B8 clones. The total amount of new vessel formation was far higher in FGF-2
      B9 tumors than in FGF-2-B8 or FGF-2-A8 tumors. Also, vessel courses were more
      irregular and blind-ending vessels and evasates were more frequent in FGF-2-B9
      tumors. Moreover, FGF-2-B9 tumor microvasculature was characterized by a wider
      average vascular diameter and by an extreme variability of the diameter of each
      individual vessel along its course between two ramifications. No statistical
      differences were observed when the distribution curves of the values of
      intervascular distances, interbranching distances, and branching angles of the
      microvessel network were compared among the different experimental groups. The
      distinctive features of the microvasculature of FGF-2-B9 tumors were retained, at
      least in part, in the smaller lesions produced by injection of a limited number
      of cells. The data indicate that FGF-2 production and release confer to FGF-2-B9
      cells the ability to stimulate the formation of new blood vessels with
      distinctive architectural features. Neovascularization of FGF-2-B9 lesions
      parallels the faster rate of growth of the neoplastic parenchyma. This does not
      affect the overall architecture of the microvessel network that appears to be
      primed by characteristics of the HEC-1-B tumor cell line and/or by the
      microenvironment of the host. To our knowledge, this work represents the first
      attempt to define the influence of a single, defined growth factor on the
      tridimensional tumor vascular pattern.

PMID- 9626065
TI  - Helicobacter pylori culture supernatant interferes with epidermal growth factor
      activated signal transduction in human gastric KATO III cells.
AB  - The mechanisms by which Helicobacter pylori infection leads to gastroduodenal
      ulceration remain poorly understood. Previous studies have shown that H. pylori
      vacuolating cytotoxin (VacA) inhibits proliferation of gastric epithelial cells,
      which suggests that H pylori may interfere with gastric mucosal repair
      mechanisms. In this study, we investigated the effects of H. pylori broth culture
      supernatants on epidermal growth factor (EGF)-mediated signal transduction
      pathways in a gastric carcinoma cell line (KATO III). Exposure of these cells to
      EGF resulted in increased expression and phosphorylation of the EGF receptor (EGF
      R), increased ERK2 activity and phosphorylation, and increased c-fos protein
      levels. Preincubation of cells with broth culture supernatant from VacA (+) H.
      pylori strain 60190 inhibited the capacity of EGF to induce each of these
      effects. In contrast, preincubation of cells with broth culture supernatant from
      an isogenic VacA-mutant strain (H. pylori 60190-v1) failed to inhibit the effects
      of EGF. These results suggest that the H. pylori vacuolating cytotoxin interferes
      with EGF-activated signal transduction pathways, which are known to be essential
      for cell proliferation and ulcer healing.

PMID- 9626066
TI  - Antigen-dependent progression of mucosa-associated lymphoid tissue (MALT)-type
      lymphoma in the stomach. Effects of antimicrobial therapy on gastric MALT
      lymphoma in mice.
AB  - In humans, low-grade B-cell mucosa-associated lymphoid tissue (MALT) lymphomas of
      the stomach regress when Helicobacter pylori infection is cured by antimicrobial
      therapy. Using an animal model of human gastric MALT lymphoma, we observed the
      effects of Helicobacter felis eradication and the relationship between infection
      and disease progression. Antimicrobial therapy was given to one-half of the
      BALB/c mice infected with H. felis for 20 months. Groups of antibiotic-treated
      and untreated mice were killed 2, 3, and 4 months after antimicrobial therapy
      (ie, 22, 23, and 24 months after infection). The numbers of mice with MALT
      decreased after H. felis eradication with no lymphoid follicles seen 4 months
      after treatment. MALT lymphoma was present in a total of 23% (11/48) of
      antibiotic-treated infected mice compared with 75% (27/36) in untreated infected
      mice. These lymphomas were further graded into low-, intermediate-, and high
      grade lymphoma. In the untreated mice, lymphoma development was more advanced
      with 36% low-grade (13/36), 39% intermediate-grade (14/36), and 6% high-grade
      (large B-cell) lymphoma (2/36) whereas in the treated mice the incidence was 21%
      (10/48), 6% (3/48), and 0% (0/48), respectively. These observations suggest that
      antigenic stimulation by H. felis sustained growth and progression of low-grade
      MALT lymphoma and that primary high-grade gastric lymphomas can evolve from the
      transformation of these tumors. Eradication of the organism caused low-grade
      tumors to regress, with inhibition or slowing down of lymphoma development toward
      high-grade lymphoma. The H. felis mouse model of gastric MALT lymphoma presents
      an opportunity to address the issues arising from antimicrobial treatment of
      these tumors in humans.

PMID- 9626067
TI  - Quantitation of amyloid beta-protein (A beta) in the cortex during aging and in
      Alzheimer's disease.
AB  - In this study we sought to learn about when and how amyloid beta-protein (A beta)
      accumulates in the cortex of normal individuals and about the difference in the A
      beta accumulation between normal aged and Alzheimer's disease (AD) brains. From
      consecutive autopsy cases and AD cases, hippocampus CA1 and occipitotemporal
      cortex T4 were sampled for A beta quantitation by the well characterized two-site
      enzyme immunoassays (EIAs). There was a strong tendency toward A beta 42
      accumulation between the ages of 50 and 70 years in T4 and a little later in CA1.
      The A beta 42 levels were consistently higher in T4 than those in CA1 in any
      given case. The levels of A beta 42 in AD brains were significantly higher than
      those in control brains, and the extent of A beta 42 amino-terminal modification
      was also much greater in AD brains than that in control brains. Even in cases in
      which no senile plaques were immunocytochemically detected, EIAs clearly showed
      that significant amounts of A beta 42 already had accumulated. In contrast to A
      beta 42, A beta 40 showed no apparent age-dependent accumulation, and its high
      levels were found to be associated with AD.

PMID- 9626068
TI  - Effects of platelet-derived endothelial cell growth factor/thymidine
      phosphorylase, substrate, and products in a three-dimensional model of
      angiogenesis.
AB  - Platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD
      ECGF/TP) is associated with angiogenesis and the progression of human breast and
      ovarian cancers. The aim of this study was to obtain information about the
      possible mechanisms of PD-ECGF/TP activity in an established three-dimensional
      model of angiogenesis. The plan was to study the effects of the enzyme,
      substrate, products, and further metabolites on the formation and rate of
      microvessel growth from cultured segments of rat aorta in serum-free media. The
      end-points were the number and length of microvessels compared with controls
      after 4, 7, 11, and 14 days in culture. Thymidine (10 to 1000 mumol/L), thymidine
      5'-monophosphate (1000 mumol/L), and 2'-deoxy-D-ribose-1-phosphate (1000 mumol/L)
      inhibited the number of microvessels produced. Conversely PD-ECGF/TP (50 to 100
      ng/ml) and beta-amino-iso-butyric acid (1000 mumol/L--a metabolite of thymine)
      had a significant stimulatory effect (P < 0.05, P < 0.01, P < 0.001 respectively
      on culture day 11). PD-ECGF (10 ng/ml), beta-amino-iso-butyric acid (1000
      mumol/L), and 2-deoxy-D-ribose (100 to 1000 mumol/L) significantly (P < 0.001, P
      < 0.01, P < 0.01, respectively) stimulated microvessel elongation by day 11. We
      conclude that PD-ECGF/TP may affect angiogenesis by changing the relative
      concentrations of pyrimidine-based compounds and their metabolites in
      interstitial fluid surrounding endothelial cells. Drugs that inhibit PD-ECGF/TP
      activity may therefore delay abnormal angiogenesis and the progression of various
      cancers.

PMID- 9626069
TI  - Lipoproteins modulate expression of the macrophage scavenger receptor.
AB  - Macrophage scavenger receptors (MSR) bind and internalize oxidized low density
      lipoprotein (OxLDL), a modified lipoprotein that is thought to be the proximal
      source of lipids that accumulate within cells of atherosclerotic lesions. The
      role of lipoproteins in modulating MSR expression are undetermined. We studied
      the effect of lipoproteins, native and modified LDL (acetylated LDL (AcLDL) and
      OxLDL) on the expression of the MSR in RAW cells, a murine macrophage cell line.
      Exposure to lipoproteins resulted in a marked induction of MSR mRNA expression
      (12- to 17-fold) with OxLDL and AcLDL having the greatest effects. Maximum
      induction occurred 1 hour after treatment with OxLDL and LDL. AcLDL induced a
      fourfold increase at 1 hour followed by a return to baseline and peak expression
      (sixfold) at 14 hours. Scavenger receptor function, as measured by 125I-AcLDL
      binding, was only modestly increased in response to lipoproteins. Incubation of
      macrophages with a cholesterol acceptor particle resulted in a dose-dependent
      decrease in MSR mRNA expression, which paralleled cholesterol loss from the
      cells. OxLDL did not affect MSR mRNA stability, implying that MSR mRNA was
      transcriptionally regulated by lipoproteins. Finally, peritoneal macrophages were
      isolated from mice following intraperitoneal injection of lipoproteins.
      Macrophage expression of MSR mRNA was significantly (16-fold) increased by LDL,
      AcLDL, or OxLDL relative to mice infused with phosphate-buffered saline. This
      demonstration that exposure to lipoproteins increases expression of the
      macrophage scavenger receptor implies that lipoproteins can further contribute to
      foam cell development in atherosclerosis.

PMID- 9626070
TI  - Immunophenotypic characterization of plasma cells from monoclonal gammopathy of
      undetermined significance patients. Implications for the differential diagnosis
      between MGUS and multiple myeloma.
AB  - Although the immunophenotype of plasma cells (PCs) from multiple myeloma (MM)
      patients has been extensively explored, information on the phenotypic
      characteristics of PCs in monoclonal gammopathy of undetermined significance
      (MGUS) patients is scanty and frequently controversial. Thus, the question of
      whether or not PCs are phenotypically different in the two disorders and whether
      this criteria could be useful for the differential diagnosis between MGUS and MM
      remains to be explored. In the present study, the immunophenotypic profile of
      bone marrow PCs (BMPCs) from a group of 76 MGUS patients has been analyzed by
      flow cytometry and compared with that of BMPCs present in both MM patients (n =
      65) and control subjects (n = 10). For that purpose, a large panel of monoclonal
      antibodies against PC-related antigens was used together with a sensitive
      methodology in which a minimum of 10(3) PCs were studied. In all MGUS cases
      studied, two clearly defined and distinct PC subpopulations could be identified.
      One PC subpopulation, population A (33 +/- 31% of total PCs), constantly
      displayed a high CD38 expression with low forward light scatter (FSC)/side light
      scatter (SSC) and was positive for CD19 and negative for CD56 (only a small
      proportion of these PCs were weakly positive for CD56). The other PC
      subpopulation, population B (67 +/- 31% of total PCs), showed the opposite
      pattern; the antigen CD56 was strongly positive and CD19 was constantly negative,
      and it showed a lower CD38 expression and higher FSC/SSC values than population
      A. Clonality studies (cytoplasmic light chain restriction, DNA content studies,
      and polymerase chain reaction assessment) confirmed the clonal nature of PCs from
      population B and the polyclonal origin of PCs from population A. Moreover, the
      polyclonal PCs from MGUS displayed a phenotypic profile identical to that found
      in PCs from healthy individuals. By contrast, clonal PCs from all MGUS patients
      displayed a similar antigenic profile to myelomatous PCs, with clear phenotypic
      differences with respect to normal PCs: lower intensity of CD38 expression and a
      variable reactivity for markers that were not expressed in normal PCs, such as
      CD28, CD117, and sIg. Although the presence of residual polyclonal PCs was a
      constant finding in MGUS patients, it was a rare event in MM and, when present
      (only 22% of MM cases), its frequency was significantly lower than that observed
      in MGUS (0.25% versus 32.9%, respectively; P < 0.0001). Only 1.5% of patients
      with MM had more than 3% of normal PCs, whereas 98% of patients with MGUS had
      more than 3%. Moreover, as shown by multivariate analysis, the number of residual
      polyclonal PCs was the most powerful single parameter for the discrimination
      between MGUS and MM patients at diagnosis, even when only stage I MM cases were
      considered.

PMID- 9626073
TI  - The Association of Professors of Dermatology and their conference on
      undergraduate teaching.

PMID- 9626071
TI  - Mouse model of angiogenesis.
AB  - Neovascularization of ischemic muscle may be sufficient to preserve tissue
      integrity and/or function and may thus be considered to be therapeutic. The
      regulatory role of vascular endothelial growth factor (VEGF) in therapeutic
      angiogenesis was suggested by experiments in which exogenously administered VEGF
      was shown to augment collateral blood flow in animals and patients with
      experimentally induced hindlimb or myocardial ischemia. To address the possible
      contribution of postnatal endogenous VEGF expression to collateral vessel
      development in ischemia tissues, we developed a mouse model of hindlimb ischemia.
      The femoral artery of one hindlimb was ligated and excised. Laser Doppler
      perfusion imaging (LDPI) was employed to document the consequent reduction in
      hindlimb blood flow, which typically persisted for up to 7 days. Serial in vivo
      examinations by LDPI disclosed that hindlimb blood flow was progressively
      augmented over the course of 14 days, ultimately reaching a plateau between 21
      and 28 days. Morphometric analysis of capillary density performed at the same
      time points selected for in vivo analysis of blood flow by LDPI confirmed that
      the histological sequence of neovascularization corresponded temporally to blood
      flow recovery detected in vivo. Endothelial cell proliferation was documented by
      immunostaining for bromodeoxyuridine injected 24 hours before each of these time
      points, providing additional evidence that angiogenesis constitutes the basis for
      improved collateral-dependent flow in this animal model. Neovascularization was
      shown to develop in association with augmented expression of VEGF mRNA and
      protein from skeletal myocytes as well as endothelial cells in the ischemic
      hindlimb; that such reparative angiogenesis is indeed dependent upon VEGF up
      regulation was confirmed by impaired neovascularization after administration of a
      neutralizing VEGF antibody. Sequential characterization of the in vivo,
      histological, and molecular findings in this novel animal model thus document the
      role of VEGF as endogenous regulator of angiogenesis in the setting of tissue
      ischemia. Moreover, this murine model represents a potential means for studying
      the effects of gene targeting on nutrient angiogenesis in vivo.

PMID- 9626074
TI  - Problems of medical education.

PMID- 9626072
TI  - Tuberculin-induced delayed-type hypersensitivity reaction in a model of hu-PBMC
      SCID mice grafted with autologous skin.
AB  - We have developed an animal model to study human delayed-type hypersensitivity
      reactions. Previous studies in humans have shown after tuberculin injection the
      presence of a mononuclear cell infiltration, with almost no eosinophils,
      associated with a preferential Th-1-type cytokine profile. Human skin graft
      obtained from tuberculin-reactive donors was grafted onto the back of severe
      combined immunodeficient mice. After healing, mice were reconstituted
      intraperitoneally with peripheral mononuclear cells. Tuberculin and diluent were
      injected intradermally, and skin biopsies were performed 72 hours later. Skin
      grafts were divided into two parts, one for immunohistochemistry and one for in
      situ hybridization studies. Immunohistochemistry was performed on cryostat
      sections using the alkaline phosphatase anti-alkaline phosphatase technique. In
      the tuberculin-injected sites as compared with the diluent-injected sites, there
      were significant increases in the number of CD45+ pan leukocytes and CD4+, CD8+,
      CD45RO+ T cells but not in CD68+ monocytes/macrophages and EG2 or MBP+
      eosinophils. The activation markers CD25 and HLA-DR were up-regulated in the
      tuberculin-injected sites. In situ hybridization was performed using 35S-labeled
      riboprobes for interleukin (IL)-2, interferon (IFN)-gamma, IL-4, and IL-5. After
      tuberculin injection, a preferential Th-1-type cytokine profile was observed with
      significant increases in the numbers of IL-2 and IFN-gamma mRNA-expressing cells.
      These results are similar to those reported after tuberculin-induced delayed-type
      hypersensitivity in humans, suggesting that this model might be useful to study
      cutaneous inflammatory reaction.

PMID- 9626075
TI  - Goals of undergraduate teaching in dermatology.

PMID- 9626076
TI  - Evaluation in dermatology.

PMID- 9626077
TI  - What do we teach?

PMID- 9626078
TI  - Acanthosis nigricans and congenital total lipodystrophy. Associated anomalies
      observed in two siblings.

PMID- 9626079
TI  - Congenital lipodystrophic diabetes with acanthosis nigricans. The Seip-Lawrence
      syndrome.

PMID- 9626081
TI  - Seborrheic verruca and intraepidermal basal cell epithelioma of Jadassohn.

PMID- 9626080
TI  - Capillary aneurysms of the skin.

PMID- 9626082
TI  - Factitial scalp lesions resembling cylindroma. Report of two cases.

PMID- 9626083
TI  - Nail in lichen planus.

PMID- 9626084
TI  - Disseminated pruriginous angiodermatitis (itching purpura).

PMID- 9626085
TI  - Bilateral nevus Ota associated with nevus Ito. A case of pigmentation on the
      lips.

PMID- 9626086
TI  - An annular verruca.

PMID- 9626087
TI  - Peculiar nail dystrophy caused by an enchondroma.

PMID- 9626088
TI  - Photosensitivity reaction to chlordiazepoxide.

PMID- 9626089
TI  - Treatment of eyelid carcinoma.

PMID- 9626090
TI  - Tolnaftate, a potent topical antifungal agent.

PMID- 9626091
TI  - Histochemistry and cytochemistry of human skin. XXVI. alkaline phosphatase
      activity in the sensory nerve endings of the clitoris.

PMID- 9626092
TI  - Do treponemes survive adequate treatment of late syphilis?

PMID- 9626093
TI  - Physiologic changes in vitiligo.

PMID- 9626094
TI  - A study of the lesion of vitiligo.

PMID- 9626096
TI  - Reactive pseudolymphoma, nodular type.

PMID- 9626095
TI  - Carcinoma of areola and nipple of the breast: Paget's disease versus carcinoma in
      situ.

PMID- 9626097
TI  - Squamous cell epithelioma.

PMID- 9626098
TI  - For diagnosis: scleroderma? Idiopathic atrophoderma of Pacini and Pierini?

PMID- 9626099
TI  - Malignant acanthosis nigricans.

PMID- 9626100
TI  - Benign acanthosis nigricans.

PMID- 9626101
TI  - Purpura of unresolved cause.

PMID- 9626102
TI  - Cutaneous angiopathy and solitary renal cysts (coincidental or related?).

PMID- 9626103
TI  - Lichen nitidus.

PMID- 9626104
TI  - Clinical review 95: Acute and prolonged critical illness as different
      neuroendocrine paradigms.

PMID- 9626105
TI  - Clinical review 96: Differential control of gonadotropin secretion in the human:
      endocrine role of inhibin.
AB  - Although considerable strides have been made in charting the physiology and
      pathophysiology of inhibin in the human, further progress awaits the development
      of recombinant inhibin suitable for administration in human studies. Measurements
      of total serum inhibin, although inadequate to chart the dynamic changes
      associated with normal and disordered pituitary-gonadal function, have proven to
      be of value as indices of ovarian tumor activity. Although the roles of specific
      dimeric inhibin measurements in clinical practice have not been clearly
      established, advances in our understanding of inhibin physiology and
      pathophysiology in the human suggest that inhibin B may have value as a marker of
      Sertoli cell function in men with infertility and as a prognostic indicator in
      women undergoing ovulation induction therapy.

PMID- 9626106
TI  - A healthy body in a healthy mind--and vice versa--the damaging power of
      "uncontrollable" stress.

PMID- 9626107
TI  - Glucocorticoid receptor polymorphism, skin vasoconstriction, and other metabolic
      intermediate phenotypes in normal human subjects.
AB  - Genetic variation of the glucocorticoid receptor (GR) locus is associated with
      differences in blood pressure. To define the intermediate phenotypes associated
      with this variation, we investigated the biochemical and clinical significance of
      a BclI restriction fragment length polymorphism of the GR locus in 64 normal male
      volunteers. Blood samples were genotyped as either AA (homozygous large allele; n
      = 6), Aa (heterozygous; n = 51), or aa (homozygous small allele, n = 7). Four
      primary glucocorticoid variables were measured including GR binding
      characteristics and glucocorticoid-sensitive lysozyme release of leukocytes in
      vitro and the blanching response of forearm skin to budesonide. A large number of
      secondary variables (urinary and plasma steroid measurements, blood pressure and
      indices of body fat metabolism, and routine biochemical and hematological
      measurements) were also considered. In vivo sensitivity to budesonide was greater
      in AA than aa individuals (mean +/- SE EC50 values: 13 +/- 5 and 42 +/- 10 ng; P
      < 0.01). In contrast, leukocytes of AA subjects tended to have lower affinity and
      reduced sensitivity for dexamethasone, although these effects were not
      statistically significant. Based on urinary steroid measurements, 11 beta
      hydroxysteroid dehydrogenase activity [ratio of tetrahydrocortisol (THF) to
      tetrahydrocortisone (THE) metabolites] was not affected by genotype. The relative
      activities of 5 alpha- and 5 beta-reductase activity (allo-THF/THF + THE)
      appeared lower in AA than aa subjects (0.22 +/- 0.04 cf. 0.33 +/- 0.06; P <
      0.005) but were not judged to be significantly different when corrected for
      multiple comparisons. Single and multivariate analyses were carried out to
      determine which variables influence GR binding characteristics and glucocorticoid
      responsiveness and to see whether cardiovascular risk factors (blood pressure and
      body fat) were influenced by glucocorticoid-dependent functions. Only 15-20% of
      the variations in the dissociation constant (Kd) and maximum binding capacity
      (Bmax) were influenced by other variables; plasma cholesterol was the most
      important for affinity and plasma sodium concentration for binding capacity.
      Multivariate analysis showed that several factors including GR genotype and
      urinary cortisol account for 10% of the variation of in vivo responses to
      glucocorticoid hormones; plasma calcium concentration was the only variable that
      contributed to in vitro sensitivity of leukocytes to dexamethasone.
      Glucocorticoid-dependent responses were of negligible importance in determining
      blood pressure or percentage body fat within the narrow physiological ranges of
      the present study. We conclude that GR genotype affects steroid sensitivity in a
      tissue-specific manner because of altered GR function or possibly because of
      linkage to a locus that controls hormone access to the receptor by influencing
      steroid metabolism.

PMID- 9626108
TI  - Stress-related cortisol secretion in men: relationships with abdominal obesity
      and endocrine, metabolic and hemodynamic abnormalities.
AB  - Abdominal obesity has been suggested to be associated with perturbations of the
      regulation of the hypothalamic-pituitary-adrenal (HPA) axis. In a population of
      51-yr-old men (n = 284) salivary cortisol concentrations were determined on
      repeated (n = 7) occasions over a random working day, and perceived stress was
      reported in parallel. Cortisol values were then related to reported stress
      (stress-related cortisol). A standardized lunch was used as a physiological
      challenge. A low dose (0.5 mg) dexamethasone suppression test was also performed
      as well as determinations of testosterone and insulin-like growth factor I (IGF
      I). Body mass index [weight (kilograms)/height (meters)2]; waist/hip
      circumference ratio (WHR); sagittal trunk recumbent diameter (D); fasting
      insulin; blood glucose; triglycerides; and total, low density (LDL), and high
      density (HDL) lipoprotein cholesterol were also determined. Cortisol
      concentrations were highest in the morning, and lunch was followed by a peak (P =
      0.044). Two types of diurnal cortisol curves were identified, one characterized
      by a high variability with high morning values, and another with low variability
      and low morning values. Both correlated strongly with suppression of salivary
      cortisol by dexamethasone (P < 0.001). Stress-related cortisol secretion was
      associated with D (P = 0.051), low IGF-I (P = 0.006), and diastolic blood
      pressure (P = 0.078). When the type of diurnal cortisol curve was taken into
      consideration by statistical weighting, stress-related cortisol secretion in
      subjects with high variability showed associations with testosterone (P < 0.001),
      D, total and LDL cholesterol, diastolic blood pressure (P < 0.001), fasting
      insulin (P = 0.039), and glucose (P = 0.030) as well as, negatively,
      triglycerides (P < 0.001). When weighted for a low variability of diurnal
      cortisol secretion, stress-related cortisol secretion showed strong negative
      relationships with IGF-I, testosterone, and HDL. Furthermore, strong, consistent
      relationships (all P < 0.001) were found with obesity factors (body mass index,
      WHR, and D), and with metabolic (insulin, glucose, triglycerides, and total and
      LDL cholesterol) as well as hemodynamic variables (systolic and diastolic blood
      pressure and heart rate). These results clearly show interactions between diurnal
      cortisol secretion related to perceived stress and anthropometric, endocrine,
      metabolic, and hemodynamic variables. This seems to occur with apparently normal
      regulation of the HPA axis (high morning peaks and variability as well as
      dexamethasone suppression of cortisol), where other endocrine variables are not
      affected. With a low diurnal cortisol variation and blunted dexamethasone
      suppression, indicating abnormal regulation of the HPA axis, perceived stress
      dependent cortisol values were strongly related to perturbations of other
      endocrine axes as well as abdominal obesity with metabolic and hemodynamic
      abnormalities. Perturbations of the regulations of the HPA axis such as those
      described in combination with low dexamethasone suppressibility are known to
      follow long term overactivation of the axis by factors such as environmental
      stress.

PMID- 9626109
TI  - Glucocorticoid effects on bone.

PMID- 9626110
TI  - Alterations of bone turnover and bone mass at different skeletal sites due to
      pure glucocorticoid excess: study in eumenorrheic patients with Cushing's
      syndrome.
AB  - The aim of the present investigation was to study the effect of glucocorticoid
      excess on bone mass and turnover not influenced by other diseases known to affect
      skeleton and/or by different gonadal status and sex. We studied several markers
      of bone turnover and bone mineral density (BMD) by both quantitative computed
      tomography (at spine and forearm) and dual x-ray absorptiometry (at spine and
      three femoral sites) in 18 eugonadal female patients affected by Cushing's
      syndrome (CS) compared to 24 eugonadal healthy female subjects matched for age
      and body mass index. In CS patients, serum bone Gla protein, a marker of
      osteoblastic function, was reduced (3.28 +/- 2.3 vs. 6.47 +/- 2.5; P < 0.01), and
      bone resorption was increased, as indicated by increased urinary hydroxyproline
      (36.6 +/- 12 vs. 29.0 +/- 9.1, P < 0.05) and urinary deoxypyridinoline (22.1 +/-
      8.0 vs. 16.4 +/- 6.3; P < 0.05). BMD was significantly (P < 0.05 or P < 0.01)
      reduced at all sites, except cortical forearm, in CS patients compared to
      controls. By comparing z-scores of reduced BMD in CS patients, spinal trabecular
      BMD was found to be the most severely affected. Furthermore, disease activity, as
      measured by urinary free cortisol, was significantly correlated with bone Gla
      protein (r = -0.57; P < 0.02), urinary hydroxyproline (r = 0.57; P < 0.02),
      urinary deoxypyridinoline (r = 0.48, P < 0.05), and BMD measured at spine and
      femur. Our results show that compared to matched control subjects, female
      eumenorrheic CS patients have reduced osteoblastic function, increased bone
      resorption, and reduced BMD, and that the severity of these abnormalities is
      statistically related to the severity of disease activity, as indicated by
      urinary free cortisol. Moreover, our data suggest a site and tissue specificity
      of the effect of glucocorticoid excess on bone mass.

PMID- 9626111
TI  - Therapeutic controversy: Pancreas transplantation for type I diabetes.

PMID- 9626112
TI  - Genes control the cessation of a woman's reproductive life: a twin study of
      hysterectomy and age at menopause.
AB  - A classical twin study was performed to assess the extent to which genetic
      factors explain individual differences in age at menopause and (indications for)
      hysterectomy. It was further examined whether a genetic effect on the timing of
      the menopause was mediated through a genetic effect on age at menarche. The
      subjects were 275 monozygotic and 353 dizygotic female twin pairs. Maximum
      likelihood model fitting was used to estimate genetic and environmental variance
      components, Kaplan-Meier survival analysis was used to account for censored data,
      and the Cox proportional hazards model was used to adjust for potential
      confounders. A model specifying additive genetic and unique environmental factors
      showed the best fit to the data, yielding a heritability (h2) for age at
      menopause of 63%. The significance of the genetic effect was confirmed by the
      survival analysis and was not affected by adjustment for confounders. Both early
      and late menopause were found to be significantly influenced by genetic factors.
      Hysterectomy also showed considerable heritability (h2 = 59%), as did its two
      main indications: fibroids (h2 = 69%) and menorrhagia (h2 = 55%). The genetic
      contribution to the variance in age at menarche was estimated to be 45%, with the
      majority (37%) being due to dominant genetic effects. No correlation was found
      between age at menopause and age at menarche, suggesting different genetic
      mechanisms. This study provides convincing evidence for the importance of genetic
      factors in determining natural and surgical menopause. Understanding how genes
      control the timing of menopause and exploring whether these genes are indirectly
      associated with disease are important areas for future study.

PMID- 9626113
TI  - Intense sympathetic nerve activity in adults with hypopituitarism and untreated
      growth hormone deficiency.
AB  - Perturbations in the sympathetic nervous system may be anticipated in adults with
      hypopituitarism and untreated GH deficiency, because the syndrome is associated
      with both peripheral and central factors known to modulate sympathetic traffic.
      The higher prevalence of hypertension and increased cardiovascular
      morbidity/mortality reported in GH-deficient patients may suggest increased
      activity of the sympathetic nervous system. We recorded muscle sympathetic nerve
      activity (MSNA) in 10 hypopituitary adults with adequate hormonal replacement
      therapy except GH and in 10 healthy controls matched for age, gender, and body
      mass index to test whether hormonal aberrations in hypopituitarism and untreated
      GH deficiency are associated with an increase in sympathetic nerve traffic. Blood
      samples for insulin-like growth factor I, free T4, and TSH were taken after an
      overnight fast, followed by an oral glucose tolerance test. Direct intraneural
      recordings of MSNA were performed with a tungsten microelectrode from the
      peroneal nerve. The hypopituitary subjects had markedly increased MSNA (54 +/- 4
      bursts/min vs. 34 +/- 4 in controls; P < 0.002), which was not related to
      abdominal obesity or altered glucose metabolism. When assessed for the whole
      study group, MSNA was inversely correlated to serum insulin-like growth factor I
      (r = -0.59; P < 0.006) and TSH (r = -0.46; P < 0.04). MSNA was positively
      correlated to diastolic blood pressure (r = 0.80; P < 0.0005) in patients, but
      not in controls. The intense sympathetic discharge is suggested to be of central
      origin and may be an important underlying mechanism for the secondary
      hypertension and increased cardiovascular morbidity/mortality in this patient
      group.

PMID- 9626114
TI  - Testosterone deficiency in young men: marked alterations in whole body protein
      kinetics, strength, and adiposity.
AB  - To investigate specific effects of androgens on whole body metabolism, we studied
      six healthy lean men (mean +/- SEM age, 23.2 +/- 0.5 yr) before and after gonadal
      steroid suppression with a GnRH analog (Lupron), given twice, 3 weeks apart.
      Primed infusions of [13C]leucine, indirect calorimetry, isokinetic dynamometry,
      growth factor measurements, and percutaneous muscle biopsies were performed at
      baseline (D1) and after 10 weeks of treatment (D2); each subject served as his
      own control. Testosterone concentrations were markedly suppressed after 10 weeks
      of treatment (D1, 535 +/- 141 ng/dL; D2, 31 +/- 9). Leucine's rate of appearance
      (index of proteolysis) was markedly suppressed after 10 weeks of hypogonadism (
      13%; P = 0.01) as well as the nonoxidative leucine disposal, an index of whole
      body protein synthesis (-13%; P = 0.01) without any changes in plasma amino acid
      concentrations. All subjects studied after 10 weeks showed a decrease in fat-free
      mass, as measured by skinfold calipers and dual emission x-ray absortiometry
      scans (D1, 56.5 +/- 2.9 kg; D2, 54.4 +/- 2.5; P = 0.005), and an increase in
      percent fat mass (D1, 19.2 +/- 2.5%; D2, 22.2 +/- 2.5; P = 0.001). Rates of lipid
      oxidation decreased (-31%; P = 0.05) after treatment, with parallel changes in
      resting energy expenditure (-9%; P = 0.05). Mean and peak GH concentrations
      (measured every 10 min for 6 h) and GH production rates did not decrease after
      testosterone deficiency, with an actual increase in basal secretion (P < 0.02).
      Plasma insulin-like growth factor I (IGF-I) concentrations did not change
      significantly after 10 weeks of treatment (D1, 227 +/- 44 micrograms/L; D2, 291
      +/- 60; P = 0.08). Isokinetic dynamometry of leg extensors at 60 degrees and 180
      degrees/s was also decreased after 10 weeks of hypogonadism. Total ribonucleic
      acid (RNA) was isolated from muscle biopsy samples, and ribonuclease protection
      assays were performed using human complementary DNA clones for IGF-I, IGF-binding
      protein-4, myosin, and actin. Ten weeks after Lupron treatment, messenger RNA
      (mRNA) concentrations of IGF-I decreased significantly, whereas there was a trend
      toward higher IGF-binding protein-4 concentrations, with no change in myosin or
      actin mRNA concentrations. In conclusion, testosterone deficiency in young men is
      associated with a marked decrease in measures of whole body protein anabolism,
      decreased strength, decreased fat oxidation, and increased adiposity. These
      effects of testosterone deficiency are independent of changes in peripheral GH
      production and IGF-I concentrations, even though im IGF-I mRNA concentrations
      decrease. These data suggest a direct effect of androgens on whole body lipid and
      protein metabolism.

PMID- 9626115
TI  - Circadian and ultradian variations of leptin in normal man under continuous
      enteral nutrition: relationship to sleep and body temperature.
AB  - To determine the influence of circadian rhythmicity and sleep on the 24-h leptin
      diurnal variations, plasma leptin levels were measured at 10-min intervals over
      24 h in seven normal subjects, once during nocturnal sleep, and once after an 8-h
      shift of sleep. The subjects were submitted to constant conditions (continuous
      enteral nutrition and bed rest in controlled chambers). Body temperature and
      plasma glucose and insulin levels were measured simultaneously. During nighttime
      sleep, leptin levels increased to a maximum (109.9 +/- 2.5% of the 24-h mean) and
      then decreased to reach a nadir in the late afternoon. The mean diurnal variation
      was 18.0 +/- 3.8% of the 24-h mean. In the daytime sleep condition, leptin levels
      rose during the night of deprivation to a maximum of 104.7 +/- 2.3% of the 24-h
      mean, decreased to a minimum around 0700 h, and then rose again during diurnal
      sleep (108.4 +/- 3.1% of the 24-h mean); the mean diurnal variation was 13.4 +/-
      3.6% of the 24-h mean. ANOVA revealed a significant interaction between time of
      day and sleep effects (P < 0.05). The diurnal and the sleep-related variations of
      plasma leptin mirrored those of body temperature and roughly paralleled those of
      plasma glucose and insulin; the amplitudes of the diurnal leptin variations were
      significantly correlated with the amplitudes of the diurnal body temperature
      variations (P < 0.05). Plasma leptin levels also displayed irregular pulses of
      low amplitude (mean duration, 70 min) that were not affected by sleep, but were
      associated with a significant decrease in glucose and insulin levels (P < 0.01).
      These results demonstrate that under continuous enteral nutrition, plasma leptin
      levels are modulated by both a slight circadian component and sleep, which
      interact under normal conditions, and suggest that leptin is implicated in
      circadian thermoregulatory adjustments.

PMID- 9626116
TI  - Ovarian hyperandrogenism is associated with insulin resistance to both peripheral
      carbohydrate and whole-body protein metabolism in postpubertal young females: a
      metabolic study.
AB  - The role of endogenous androgens in enhancing the body's protein anabolic
      capacity has been controversial. To examine this question we chose to study whole
      body protein and glucose kinetics in a group of 21 young, postpubertal females
      (16.3 +/- 0.6 yr), 8 of whom had clinical and laboratory evidence of ovarian
      hyperandrogenism (OH) (BMI = 37.8 +/- 1.3 kg/m2). We used L-[1-13C]leucine and
      [6,6,2H2]glucose tracer infusions before and after suppression of their
      endogenous androgens with estrogen/progesterone supplementation in the form of
      Triphasil for 4 weeks. Their baseline data were also compared with those of
      similar aged girls, 7 obese (OB) (BMI = 36.4 +/- 1.5) and 6 lean (LN) (BMI = 20.9
      +/- 0.7) who were normally menstruating and had no evidence of androgen excess.
      Despite comparable glucose concentrations, both OH and OB groups had significant
      hyperinsulinemia (OH > OB), both basally and after iv glucose stimulation, as
      compared to LN controls (basal insulin: OH, 252 +/- 52 pmol/L; OB, 145 +/- 41;
      LN, 60 +/- 9, P = 0.009 OH vs. LN; peak insulin: OH, 2052 +/- 417; OB, 1109 +/-
      127, LN, 480 +/- 120, P = 0.0009 OH vs. LN). The rate of appearance (Ra) of
      glucose, a measure of glucose production, was greater in the LN controls than in
      the OH or OB groups (OH, 2.0 +/- 0.1 mg/kg.fat free mass.min; OB, 1.9 +/- 0.1;
      LN, 3.3 +/- 0.1, P < 0.004 vs. LN). Calculated total rates of whole-body protein
      breakdown (leucine Ra), oxidation, and protein synthesis (nonoxidative leucine
      disposal) were substantially higher in the OH and OB groups as compared with LN
      controls (P < 0.04 vs. LN); however, when data are expressed on a per kilogram of
      fat free mass basis, the OH group had higher rates of proteolysis than the OB and
      LN, with indistinguishable rates between the latter two groups. None of the above
      mentioned parameters changed after 1 month of administration of Triphasil,
      despite marked improvement in circulating testosterone and free testosterone
      concentrations after treatment (testosterone, -50%, P = 0.003; free testosterone,
      -70%, P = 0.02). We conclude that obesity in young postpubertal females is
      associated with insulin resistance for both peripheral carbohydrate and protein
      metabolism, and that patients with the OH syndrome have even greater insulin
      resistance as compared with simple obesity, regardless of treatment for the
      androgen excess. Carefully designed studies targeting interventions to improve
      both the hyperandrogenic and hyperinsulinemic state may prove useful even in the
      early juvenile stages of this disease.

PMID- 9626117
TI  - Risedronate, a highly effective oral agent in the treatment of patients with
      severe Paget's disease.
AB  - Thirteen patients with severe Paget's disease of bone [mean serum alkaline
      phosphatase (SAP) level 17 times the upper limit of normal] were treated with 30
      mg oral risedronate daily for 8 weeks. Patients were followed for 16 weeks
      without treatment. The change from baseline SAP was the primary end point. Those
      patients whose SAP levels did not reach the normal range were retreated with 30
      mg for another 8 weeks. There was a mean percent decrease in SAP of 77% after the
      first course of risedronate treatment and 87% after the second course of
      treatment. All patients who completed the study had a decrease in SAP of at least
      77% from the baseline. The urinary hydroxyproline/creatinine level was decreased
      by 64% and 79%, respectively, during the first and second treatment courses.
      There were transient asymptomatic decreases in serum calcium and phosphorus
      levels. The urinary calcium/creatinine ratio also decreased in these patients.
      Serum intact PTH and 1,25-dihydroxyvitamin D levels increased transiently during
      risedronate treatment. Oral risedronate was well tolerated by the patients. Only
      one patient discontinued treatment because of an adverse event (diarrhea) thought
      to be related to risedronate therapy.

PMID- 9626118
TI  - Beneficial effect of diazoxide in obese hyperinsulinemic adults.
AB  - Hyperinsulinemia, insulin resistance, and increased adipose tissue are hallmarks
      of the obesity state in both humans and experimental animals. The role of
      hyperinsulinemia as a possible preceding event in the development of obesity has
      been proposed. We previously demonstrated that administration of diazoxide (DZ),
      an inhibitor of insulin secretion, to obese hyperinsulinemic Zucker rats resulted
      in less weight gain, enhanced insulin sensitivity, and improved glucose
      tolerance. Assuming that hyperinsulinemia plays a major role in the development
      of human obesity, then its reversal should have therapeutic potential. To test
      this hypothesis, we conducted a randomized placebo-controlled trial in 24
      hyperinsulinemic adults [body mass index (BMI) > 30 kg/m2]. All subjects were
      placed on a low-calorie (1260 for females and 1570 for males) Optifast (Sandoz,
      Minneapolis, MN) diet. After an initial 1-week lead-in period, 12 subjects (mean
      +/- SE for age and BMI, 31 +/- 1 and 40 +/- 2, respectively) received DZ (2 mg/kg
      BW.day; maximum, 200 mg/day, divided into 3 doses) for 8 weeks; and 12 subjects
      (mean +/- SE for age an BMI, 28 +/- 1 and 43 +/- 1, respectively) received
      placebo. Compared with the placebo group, DZ subjects had greater weight loss
      (9.5 +/- 0.69% vs. 4.6 +/- 0.61%, P < 0.001), greater decrease in body fat (P <
      0.01), greater increase in fat-free mass to body fat ratio (P < 0.01), and
      greater attenuation of acute insulin response to glucose (P < 0.01). However,
      there was no significant difference in insulin sensitivity and glucose
      effectiveness, as determined by the insulin-modified i.v. glucose tolerance test
      (Bergman's minimal model) and no significant difference in glycohemoglobin
      values. CONCLUSION: 8 weeks treatment with DZ had a significant antiobesity
      effect in hyperinsulinemic obese adults without inducing hyperglycemia.

PMID- 9626119
TI  - A defect in renal calcium conservation may contribute to the pathogenesis of
      postmenopausal osteoporosis.
AB  - Although all postmenopausal women are estrogen deficient, women who have
      postmenopausal osteoporosis may have a defect, in addition to estrogen
      deficiency, that accounts for their higher rates of bone resorption and greater
      bone loss, relative to those who do not. To test the hypothesis that one defect
      is an impairment in renal calcium conservation, we measured renal calcium
      transport in 19 osteoporotic and 19 normal postmenopausal women, whose ages
      (median and 25th-75th percentile range) were 70 yr (range, 67-72) and 72 yr
      (range, 69-74), respectively. There was no difference between groups in values
      for serum ionized calcium and PTH concentrations or in renal filtered load of
      calcium. However, before PTH infusion, the osteoporotic women had lower (P =
      0.0046) values for tubular reabsorption of calcium (TRCa) of 96.8% (range, 96.0
      97.1) vs. 98.0% (range, 97.2-98.3) and higher (P = 0.0154) urinary calcium
      excretion of 0.194 mg/dL of glomerular filtrate (GF) (0.154-0.239) vs. 0.125
      mg/dL of GF (0.103-0.173) than the normal women. After infusion of 200 U of
      synthetic PTH (synthetic 1-34 analog of human PTH), TRCa increased and calcium
      excretion decreased comparably in both groups, so that the differences between
      groups after intervention remained: for TRCa, 98.3% (97.7-98.6) vs. 98.9% (98.4
      99.3; P = 0.0042); and for calcium excretion, 0.099 mg/dL of GF (0.080-0.138) vs.
      0.066 mg/dL of GF, (0.045-0.097, P = 0.0180). In conclusion, postmenopausal women
      with osteoporosis have a PTH-independent defect in renal calcium conservation.
      This defect is of sufficient magnitude to contribute to the greater negative
      calcium balance in post-menopausal women with osteoporosis vs. their
      postmenopausal peers.

PMID- 9626120
TI  - Effects of short-term calcium depletion and repletion on biochemical markers of
      bone turnover in young adult women.
AB  - The skeletal responses to calcium depletion and repletion in rodents have been
      well characterized, but those in humans are poorly understood. The present study
      sought to evaluate the effects of short term dietary calcium depletion and
      repletion on biochemical markers of bone turnover in 15 young Caucasian women
      (age, 21-30 yr). The study contained 3 phases: 1) 5 days of a regular diet
      containing more than 800 mg/day calcium to establish baseline values (baseline
      phase), 2) 22 days of a restricted diet containing less than 300 mg/day calcium
      (depletion phase), and 3) 7 days of a normal diet containing more than 800 mg/day
      calcium (repletion phase). Serum and urine samples were obtained from each
      subject during the baseline phase; on the first, second, and last days of the
      depletion phase; and on the third and last days of the repletion phase. Serum
      levels of calcium, PTH, 1,25-dihydroxyvitamin D3, osteocalcin, and C-terminal
      type I procollagen peptide (PICP) and urinary levels of calcium and
      deoxypyridinoline were determined. Serum and urinary calcium levels were
      significantly reduced, and serum PTH and 1,25-dihydroxyvitamin D3 levels were
      markedly increased during depletion. These changes were completely reversed after
      1 week of repletion. Depletion also rapidly and significantly increased the
      urinary deoxypyridinoline level, indicating increased bone resorption. The
      increase also returned rapidly to baseline upon repletion. Calcium depletion had
      contrasting effects on bone formation markers; whereas depletion significantly
      reduced the serum PICP level, it significantly increased serum osteocalcin level.
      Past histomorphometric studies in rodents indicated that the number of mature but
      inactive osteoblasts was increased during depletion despite an inhibition of bone
      formation. Thus, it is speculated that although the reduction in serum PICP
      reflected the depletion-associated inhibition of bone formation, the increase in
      serum osteocalcin could represent this depletion-related increase in osteoblast
      number. During repletion, serum osteocalcin remained elevated above baseline.
      PICP recovered from its depressed level and increased above baseline, a finding
      consistent with past histomorphometric findings of increased bone formation
      during repletion. In summary, this study confirms that 1) a short calcium
      depletion period produces calcium stress in young women, which leads to rapid
      stimulation of bone resorption and inhibition of bone formation; and 2) a
      subsequent calcium repletion period could lead to a compensatory increase in bone
      formation. In conclusion, the skeletal responses to calcium depletion/ repletion
      in young women may be similar to those in rodents.

PMID- 9626121
TI  - Oral dehydroepiandrosterone for adrenal androgen replacement: pharmacokinetics
      and peripheral conversion to androgens and estrogens in young healthy females
      after dexamethasone suppression.
AB  - Women with adrenal insufficiency suffer from chronic dehydroepiandrosterone
      (sulfate) [DHEA(S)] deficiency. To define a suitable dose for DHEA replacement,
      we studied the pharmacokinetics and biotransformation of orally administered DHEA
      in nine healthy female volunteers (mean age 23.3 +/- 4.1 yr, mean body mass index
      22.5 +/- 1.8 kg/m2) with transient suppression of adrenal androgen secretion
      because of dexamethasone (dex) administration (4 x 0.5 mg/day for 4 days).
      Diurnal blood sampling was performed during the early follicular phase of four
      subsequent menstrual cycles (study period 1: baseline; study periods 2-4: dex +
      placebo, dex + 50 mg DHEA or dex + 100 mg DHEA in a randomized cross-over
      design). Dex induced not only a significant suppression of serum cortisol (to 8%
      of baseline) but also of DHEA (18%), DHEA(S) (16%), and androstenedione (26%), as
      well as of testosterone (28%), dihydrotestosterone (43%), and estrone (54%). Oral
      administration of 50 mg DHEA led to restoration of DHEA(S) baseline levels,
      whereas 100 mg induced supraphysiological concentrations [baseline vs. 50 mg DHEA
      vs. 100 mg DHEA: area under the concentration-time curve (AUC) 0-12 h DHEA: 280
      +/- 85 vs. 241 +/- 73 vs. 383 +/- 106 nmol/L x h; AUC 0-12 h DHEA(S): 89.1 +/-
      48.4 vs. 139.6 +/- 43.5 vs. 213.3 +/- 21.6 mumol/L x h). Serum concentrations of
      dihydrotestosterone and estrone were restored to baseline after 50 mg DHEA,
      whereas baseline testosterone and androstenedione levels were only achieved by
      administration of 100 mg DHEA. In conclusion, 50 mg DHEA seems to be a suitable
      replacement dose in females with adrenal insufficiency. Furthermore, the rapid
      and lasting conversion to potent androgens demonstrates a potential role of DHEA
      for androgen replacement in females in general.

PMID- 9626122
TI  - Insulin-like growth factor binding protein-I levels are strongly associated with
      insulin sensitivity and obesity in early pubertal children.
AB  - In conditions associated with insulin resistance, insulin-like growth factor
      binding protein-I (IGFBP-I) levels have been shown to correlate inversely with
      insulin levels. Puberty is associated with insulin resistance and thus provides a
      model for comparing the relationship of IGFBP-I to both insulin levels and
      measures of insulin sensitivity. Our study population consisted of 104 healthy
      pubertal children, age 9.8-14.6 yr. Each subject had his/her insulin sensitivity
      (Si) assessed by the modified minimal model of Bergman, which employs a
      frequently sampled i.v. glucose tolerance test. Results showed that IGFBP-I
      levels were significantly higher in boys than in pubertally matched girls (P <
      0.01). There was a strong positive correlation between IGFBP-I levels and Si (r =
      0.65, P < 0.0001) and a weaker negative correlation with fasting insulin levels
      (r = -0.38, P < 0.0001). An inverse relationship was also found between IGFBP-I
      levels and body mass index (r = -0.46, P < 0.0001) and with IGF-I levels (girls
      only, r = -0.41, P < 0.003). Consequently, insulin sensitivity, obesity, and IGF
      I are important predictors of IGFBP-I levels in pubertal children. It is possible
      that insulin-mediated suppression of IGFBP-I in obese children may increase free
      IGF-I levels and thus contribute to somatic growth. The same mechanism may
      operate in pubertal children, where insulin resistance and growth acceleration
      occur simultaneously.

PMID- 9626123
TI  - Study of a kindred with classic congenital adrenal hyperplasia: diagnostic
      challenge due to phenotypic variance.
AB  - We sought to determine the concordance of the phenotype and genotype in a kindred
      with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency. The
      variation in phenotypic expression within this family underscores the difficulty
      of establishing the diagnosis in the absence of newborn screening, even with a
      heightened index of suspicion. Steroidogenic profiles were obtained for the three
      affected siblings. The available clinical history of the two affected aunts was
      retrieved. Genotyping was performed on several members of the kindred. Detailed
      sequencing of the entire CYP21 gene of two clinically dissimilar subjects in this
      family was undertaken to explore the possibility of other mutations or
      polymorphisms. PCR with ligase detection reaction analysis of CYP21 revealed that
      the affected family members III-2, III-3, III-4, II-3, and II-4, all were
      compound heterozygotes carrying the intron 2 point mutation known to interfere
      with splicing (nucleotide 656 A to G) and the exon 4 point mutation causing a
      nonconservative substitution of asparagine for isoleucine at codon 172 (I172N).
      Detailed sequencing of the gene was performed for the two most phenotypically
      dissimilar subjects. A single silent polymorphism was found in the third
      nucleotide for codon 248 in patient II-4, but not in patient III-4, and no
      additional mutations were found. Classic congenital adrenal hyperplasia remains a
      difficult diagnosis to make in the absence of newborn screening because of the
      variability of phenotypic expression. Likewise, the variable degree of genital
      ambiguity in affected females in this family serves to question universal
      advocacy of prenatal steroid treatment in pregnancies at risk for congenital
      adrenal hyperplasia. Extensive molecular exploration did not provide an
      explanation of the phenotypic heterogeneity and supports the possibility of
      influences other than the CYP21 gene for the observed divergence.

PMID- 9626124
TI  - Specific impairment of endothelium-dependent vasodilation in subjects with type 2
      diabetes independent of obesity.
AB  - In subjects with type 2 diabetes in whom an impaired response to an endothelial
      dependent vasodilator has been characterized, the populations have also been at
      least moderately obese. Obesity has been characterized as an independent
      predictor of endothelial dysfunction in nondiabetic subjects. We hypothesized
      that in normotensive subjects with type 2 diabetes compared with age-matched
      control subjects, 1) endothelium-dependent vasodilation, as demonstrated by the
      forearm blood flow (FABF) response to intraarterial acetylcholine, would be
      decreased; 2) endothelium-independent vasodilation, as demonstrated by the FABF
      response to intraarterial nitroprusside, would be similar; 3) the degree of
      insulin resistance, as measured by the insulin sensitivity index (SI), would
      predict greater impairment in the FABF response to acetylcholine; and 4) these
      relationships would be independent of obesity. We measured FABF by venous
      occlusion plethysmography during brachial arterial infusions of the endothelium
      dependent vasodilator acetylcholine and the endothelium-independent vasodilator
      nitroprusside in 20 control and 17 subjects with type 2 diabetes. We measured SI
      using the frequently sampled i.v. glucose tolerance test. Among the diabetic
      relative to the control subjects we identified a decrease in the acetylcholine
      mediated percent increase in FABF (P = 0.02). Using the absolute FABF response to
      acetylcholine and including adjustments for body mass index and other covariates,
      the overall group difference remained and was noted to be greatest in those
      subjects who had lower baseline FABFs. In contrast, no significant difference in
      the nitroprusside-mediated increase in the percent change FABF was identified
      between groups (P = 0.30). Finally, the degree of insulin resistance, as measured
      by SI, did not independently predict greater impairment of the FABF response to
      acetylcholine. This study is the first to identify specific endothelial cell
      dysfunction that remains significant after adjustment for obesity in a population
      of normotensive subjects with type 2 diabetes.

PMID- 9626125
TI  - Normal intelligence with severe insulin-like growth factor I deficiency due to
      growth hormone receptor deficiency: a controlled study in a genetically
      homogeneous population.
AB  - Superior school performance was reported for 52 Ecuadorian probands with severe
      deficiency of insulin-like growth factor I (IGF-I) due to GH receptor deficiency
      (GHRD) resulting from homozygosity for the E180 splice mutation of the GHR. In
      contrast, subnormal intelligence was reported in a study of 18 genetically
      heterogeneous Israeli patients, attributed to frequent hypoglycemia or IGF-I
      dependence of brain development. This study is the first controlled evaluation of
      the intellectual ability of patients with GHRD. We compared the intelligence of
      18 patients of school age (mean +/- SD age, 11.5 +/- 2.8 yr), 42 of their
      relatives (11.5 +/- 2.8 yr), and 28 community controls (10.0 +/- 0.8 yr), using a
      battery of intelligence tests that have been validated in cross-cultural
      research, designed to minimize the effects of physical size, motor coordination,
      and cultural background. Because all patients had the same GHR mutation, for
      which the carrier state could be determined, this study also investigated whether
      heterozygosity for mutation of the GHR among unaffected relatives is associated
      with intelligence. The intellectual ability of the patients with GHRD was not
      significantly different from that of their relatives (P > 0.05) on the
      psychometric tests of intelligence and was comparable to that of the community
      controls on the chronometric tests. Homozygosity or heterozygosity for the
      mutation in the GHR gene common to Ecuadorian patients was unrelated to
      intelligence (P > 0.05). These results indicate that the gene defect causing GHRD
      is not related to intelligence in the Ecuadorian population. They also indicate
      that GH-induced IGF-I production is not required for normal brain growth in utero
      or for postnatal intellectual development.

PMID- 9626126
TI  - Cell-mediated immunity and postpartum thyroid dysfunction: a possibility for the
      prediction of disease?
AB  - Postpartum (pp) thyroid dysfunction (PPTD) is thought to be caused by an
      autoimmune (AI) destruction of thyroid follicles during the pp period. The
      chronic thyroid AI process [already present in pregnancy, as shown by the
      positivity for thyroid peroxidase antibodies (TPO-Ab)] becomes overt disease in
      the pp period, and one assumes that this exacerbation represents a rebound
      phenomenon after a general immunosuppression during pregnancy. The presence of
      TPO-Ab in pregnancy has been suggested as a predictor for later PPTD development.
      Apart from B cells, e.g. production of autoantibodies, various functions of the
      cell-mediated immune (CMI) system, including those of peripheral T cells,
      monocytes, and dendritic cells (DC), are also disturbed in AI states. The
      objectives of the present study were: determining alterations in various CMI
      parameters in pregnancies followed by PPTD vs. those not followed by PPTD; and
      determining the usefulness of these parameters in the prediction of PPTD. In a
      prospective study (region: Kempenland, southeast Netherlands), a random sample of
      291 women were tested at 12 and 32 weeks gestation and 4 weeks pp for TPO-Ab.
      Women were followed until 9 months pp, for developing PPTD. PPTD was defined as
      both: an abnormal TSH, and fT4 pp women developing PPTD and/or being positive for
      TPO-Ab (n = 26); and thyroidological uneventful control women of the same cohort,
      matched for age and parity (n = 21), were tested for thyroid-stimulating
      antibodies, percentages of peripheral blood lymphocyte subsets using fluorescence
      activated cell sorter analysis (CD3, CD4, CD8, CD16, CD56, major
      histocompatibility complex-class II), for monocyte polarization, and for cluster
      capability of monocyte-derived DC. Results were: 1) 31 women (10.7%) were
      positive for TPO-Ab (TPO-Ab+) in gestation (12 and/or 32 weeks); 2) 15 women
      (5.2%) developed PPTD, of whom 10 were TPO-Ab+ in gestation; 3) pregnancy-related
      CMI alterations consisted of low percentages of CD16+CD56+ natural killer (NK),
      cells and a low DC cluster capability at 12 weeks gestation (these functions were
      normalized at 32 weeks gestation); 4) the TPO-Ab+ PPTD+ women (4 hyper, 5 hypo,
      and 1 hyper/hypo) were characterized by a persistently low percentage of NK
      cells, a lowered monocyte polarization, and a raised percentage of major
      histocompatibility complex-class II+CD3+ T cells; 5) the TPO-Ab- PPTD+ women (all
      5 hyper) had neither thyroid-stimulating antibodies nor CMI alterations, apart
      from those normally seen in pregnancy; 6) 21 women were positive for TPO-Ab in
      pregnancy but did not develop PPTD (they had the same lowered NK cell percentages
      and monocyte polarization as the TPO-Ab+ PPTD+ cases, but they had normal
      percentages of activated peripheral T cells and a lower titer of TPO-Ab); 7)
      determination of the number of NK cells and monocyte polarization hardly
      contributed to the prediction of PPTD (as compared with TPO-Ab status), because
      of strong interindividual variation and close association with the presence of
      TPO-Ab; and 8) combining TPO-Ab assays with testing for activated T cells was the
      most optimal parameter for the prediction of TPO-Ab+ cases of PPTD in our small
      test set. We conclude that TPO-Ab+ pregnant women who develop PPTD show several
      CMI abnormalities other than those seen in normal pregnant women, such as
      persistently lower percentage of NK cells, a lowered monocyte polarization, and a
      raised percentage of activated T cells. The latter seems rather specific for the
      actual PPTD development and is not found in TPO-Ab+ (but PPTD) uncomplicated
      pregnancies. TPO-Ab- (but PPTD+) women had no signs of CMI abnormalities (apart
      from those specific for the pregnancy state). Although studied cases are low in
      number, our data are suggestive for the existence of two forms of PPTD: a TPO-Ab+
      (AI) form (two-thirds of patients, classical PPTD pattern); and a TPO-Ab- (non
      AI) form (one-third of patients, only hyper). Such assumption implies that, at
      best, two

PMID- 9626127
TI  - Fasting suppresses pulsatile luteinizing hormone (LH) secretion and enhances
      orderliness of LH release in young but not older men.
AB  - Pulsatile gonadotropin secretion and sex-steroid concentrations are suppressed
      reversibly in young fasted or malnourished human subjects. In this study, we
      investigated the impact of age on the dynamic neuroendocrine mechanisms
      underlying this stress response in healthy young (age, 28 +/- 3 yr, n = 8) vs.
      older (age 67 +/- 2 yr, n = 8) men with similar body mass indices (mean, 26 +/-
      0.6 vs. 26 +/- 1.3 kg/m2, respectively). Serum LH concentrations were measured by
      immunoradiometric assay (IRMA) in blood collected at 10-min intervals over 27 h
      on a control (fed) day and on the third day of a 3.5-day fast (water only)
      assigned in randomized order. After 24 h of basal sampling, GnRH (10 micrograms
      i.v. bolus) was administered to test gonadotrope responsiveness. Cortisol,
      dehydroepiandrosterone sulfate, androstenedione, testosterone, FSH, GH, and PRL
      were measured in 24-h pooled serum as positive and negative control hormones.
      Approximate entropy was used to quantitate the orderliness of LH release over 24
      h, and a multiple-parameter deconvolution method was applied to quantify
      pulsatile LH secretion and LH half-life. In the fed state, older men exhibited
      elevated mean (24-h pooled) serum FSH and cortisol concentrations compared with
      young controls but equivalent serum LH concentrations and reduced serum GH, free
      testosterone, androstenedione, and dehydroepiandrosterone sulfate concentrations.
      Fed older men also manifested a lower frequency and amplitude of 24-h pulsatile
      LH secretion, and, by approximate entropy calculations, a more disorderly pattern
      of basal LH release than younger individuals. Three- and one-half days of fasting
      evoked 40% and 47% increases in mean (24-h) serum cortisol concentrations in
      young and older men, respectively (P < 0.01 vs. fed, but P = not significant for
      percentage rise in older vs. young men). Concurrently, fasting induced a 2.1-fold
      fall in the 24-h endogenous LH production rate in young men (fed 36 +/- 9.7 vs.
      fasted 17 +/- 2.0 IU/L of distribution volume/day, P < 0.01), but did not
      significantly affect the daily LH secretion rate in older men (fed 27 +/- 4.5 vs.
      fasted 21 +/- 3.4 IU/day). The reduced LH production rate in fasting young men
      was accounted for by a 1.7-fold decline in the mass of LH secreted per burst (fed
      2.5 +/- 0.45 vs. fasted 1.5 +/- 0.16 IU/L, P < 0.05), whereas LH burst mass in
      older men remained unchanged (and low) during fasting. In addition, in young men,
      during the 3.5-day fast the number of computer-resolved LH secretory bursts per
      24 h decreased (fed 15 +/- 0.7 vs. fasted 11 +/- 0.7, P < 0.01), and the
      interburst interval increased (fed 94 +/- 4.2 vs. fasted 125 +/- 8.7 min, P <
      0.05). In contrast, in older men in the fed state, basal LH peak frequency and
      serum free testosterone concentrations were reduced compared with corresponding
      values in young men, and did not decline further with fasting. Whereas the
      orderliness of LH release patterns increased significantly during fasting in the
      young men, the approximate entropy measure failed to change significantly in
      unfed older subjects. By cosinor analysis, young men showed lower 24-h mesor
      (mean of nyctohemeral rhythm of) serum LH concentrations than older volunteers
      during fasting. Moreover, young but not older men manifested preserved 24-h
      variations in LH interpulse intervals when fasting. Exogenously stimulated LH
      release (mean 3-h serum LH concentration or calculated mass of LH secreted)
      following a single i.v. injection of 10 micrograms GnRH was independent of age
      and fasting status. We conclude that the metabolic stressor of short-term fasting
      unmasks specific age-related neuroendocrine contrasts in the stress-responsive
      control of both the pulsatile and nyctohemeral regulation of the male hypothalamo
      pituitary-gonadal-axis.

PMID- 9626128
TI  - Development of a health-related quality-of-life questionnaire (PCOSQ) for women
      with polycystic ovary syndrome (PCOS).
AB  - OBJECTIVE: To develop a self-administered questionnaire for measuring health
      related quality of life (HRQL) in women with polycystic ovary syndrome (PCOS).
      METHODS: We identified a pool of 182 items potentially relevant to women with
      PCOS through semistructured interviews with PCOS patients, a survey of health
      professionals who worked closely with PCOS women, and a literature review. One
      hundred women with PCOS completed a questionnaire in which they told us whether
      the 182 items were relevant to them and, if so, how important the issue was in
      their daily lives. We included items endorsed by at least 50% of women in the
      analysis plus additional items considered crucial by clinicians and an important
      subgroup of patients in a factor analysis. We chose items for the final
      questionnaire taking into account both item impact (the frequency and importance
      of the items) and the results of the factor analysis. RESULTS: Over 50% of the
      women with PCOS labelled 47 items as important to them. Clinicians chose 5
      additional items from the infertility domain, 4 of which were identified as
      important by women who were younger, less educated, married, and African
      American. The Cattell's Scree plot from a factor analysis of these 51 items
      suggested 5 factors that made intuitive sense: emotions, body hair, weight,
      infertility, and menstrual problems. We chose the highest impact items from these
      5 domains to construct a final questionnaire, the Polycystic Ovary Syndrome
      Questionnaire (PCOSQ), which includes a total of 26 items and takes 10-15 minutes
      to complete. CONCLUSIONS: We have used established principles to construct a
      questionnaire that promises to be useful in measuring health-related quality of
      life. The questionnaire should be tested prior to, or concurrent with, its use in
      randomized trials of new treatment approaches.

PMID- 9626129
TI  - Luteal-phase estradiol relates to symptom severity in patients with premenstrual
      syndrome.
AB  - Premenstrual syndrome (PMS) is characterized by distressing somatic and
      behavioral symptoms that develop after ovulation, reach a maximum during the
      premenstrual days, and disappear within 4 days after the onset of menstruation.
      Corpus luteum formation is necessary for the presence of symptoms, but the role
      of luteal hormones is unclear. The aim of this work was to investigate the
      relationship between sex hormone serum concentrations and premenstrual symptom
      severity in patients with PMS. Mental and physical symptoms were marked on a
      validated visual analog scale by 30 PMS patients every evening. Daily blood
      samples were taken in the luteal phase and in most of the follicular phase.
      Estradiol, progesterone, FSH, and LH were analyzed. Symptom severity was
      calculated as the number of negative symptoms expressed per day and as summarized
      scores of negative ratings. Based on premenstrual hormone concentrations and
      using the median split method, patients were divided into groups with high and
      low hormone levels. The pattern of expressed symptoms and summarized scores
      during the menstrual cycle was similar for the 2 groups. High concentration of
      luteal-phase estradiol and LH were related to the severity of negative
      premenstrual symptoms.

PMID- 9626130
TI  - Treatment of estrogen deficiency symptoms in women surviving breast cancer. The
      Hormone Foundation, Canadian Breast Cancer Research Initiative, National Cancer
      Institute of Canada, Endocrine Society, and the University of Virginia Cancer
      Center and Woman's Place.

PMID- 9626131
TI  - Insulin stimulates testosterone biosynthesis by human thecal cells from women
      with polycystic ovary syndrome by activating its own receptor and using
      inositolglycan mediators as the signal transduction system.
AB  - To determine whether insulin stimulates human ovarian testosterone production in
      the polycystic ovary syndrome by activating its own receptor and using
      inositolglycan mediators as the signal transduction system, thecal cells from
      polycystic ovary syndrome women were isolated and cultured. Insulin and insulin
      like growth factor I stimulated thecal testosterone biosynthesis. Antibody
      blockade of the insulin receptor abolished insulin's stimulatory action, whereas
      effective antibody blockade of the insulin-like growth factor I receptor did not
      alter insulin's stimulation of thecal testosterone biosynthesis. A chiro-inositol
      containing glycan (INS-2) increased thecal testosterone biosynthesis.
      Preincubation of cells with an antiinositolglycan antibody (A23939 or alpha IGP)
      abolished insulin's stimulatory effect, but not that of hCG. These findings
      suggest that inositolglycans serve as the signal transduction system for
      insulin's stimulation of human thecal testosterone biosynthesis.

PMID- 9626132
TI  - Growth hormone-binding protein directly depends on serum leptin levels in adults
      with different nutritional status.
AB  - The aim of this work was to assess the relationship between GH-binding protein
      (GHBP) and leptin. Both peptides are nutritionally regulated, but the recent
      implication of a role for leptin in the GH axis requires further study. To avoid
      the sexual dimorphism in leptin values, we performed leptin standardization
      according to gender (SD score-leptin). The relationship between SD score-leptin
      and GHBP was studied in 128 adults with different nutritional status [8 groups
      according to body mass index (BMI)], ranging from severely underweight anorexia
      nervosa to highly morbid obesity. Both GHBP and SD score-leptin significantly
      increased according to BMI within the range from 18-27 kg/m2, whereas no
      significant differences were found among underweight groups (BMI, < 18 kg/m2) or
      among obesity grades (BMI, > 27 kg/m2). We found a strong correlation between
      GHBP and SD score-leptin (r = 0.8; P < 0.0001). Multiple regression analysis
      revealed SD score-leptin to be a significant determinant of GHBP, accounting for
      64% of the variation, whereas BMI did not contribute further to explaining
      changes in GHBP. This suggests a physiological pathway involving both GHBP (the
      soluble fraction of GH receptor) and leptin. Thus, we might speculate that leptin
      could be the signal that induces the related nutritional changes observed in
      GHBP/GH receptor expression.

PMID- 9626133
TI  - Serum dehydroepiandrosterone (DHEA) and DHEA sulfate are negatively correlated
      with serum interleukin-6 (IL-6), and DHEA inhibits IL-6 secretion from
      mononuclear cells in man in vitro: possible link between endocrinosenescence and
      immunosenescence.
AB  - Interleukin-6 (IL-6) is one of the pathogenetic elements in inflammatory and age
      related diseases such as rheumatoid arthritis, osteoporosis, atherosclerosis, and
      late-onset B cell neoplasia. In these diseases or during aging, the decrease in
      production of sex hormones such as dehydroepiandrosterone (DHEA) is thought to
      play an important role in IL-6-mediated pathogenetic effects in mice. In humans,
      we investigated the correlation of serum levels of DHEA, DHEA sulfate (DHEAS), or
      androstenedione (ASD) and IL-6, tumor necrosis factor-alpha, or IL-2 with age in
      120 female and male healthy subjects (15-75 yr of age). Serum DHEA, DHEAS, and
      ASD levels significantly decreased with age (all P < 0.001), whereas serum IL-6
      levels significantly increased with age (P < 0.001). DHEA/DHEAS and IL-6 (but not
      tumor necrosis factor-alpha or IL-2) were inversely correlated (all patients: r =
      -0.242/-0.312; P = 0.010/0.001). In female and male subjects, DHEA and ASD
      concentration dependently inhibited IL-6 production from peripheral blood
      mononuclear cells (P = 0.001). The concentration-response curve for DHEA was U
      shaped (maximal effective concentration, 1-5 x 10(-8) mol/L), which may be the
      optimal range for immunomodulation. In summary, the data indicate a functional
      link between DHEA or ASD and IL-6. It is concluded that the increase in IL-6
      production during the process of aging might be due to diminished DHEA and ASD
      secretion. Immunosenescence may be directly related to endocrinosenescence,
      which, in turn, may be a significant cofactor for the manifestation of
      inflammatory and age-related diseases.

PMID- 9626134
TI  - Regulation of the growth hormone-insulin-like growth factor I axis in developing
      and adult monkeys is affected by estradiol replacement and supplementation with
      insulin-like growth factor I.
AB  - Developmental changes in the GH-insulin-like growth factor I (IGF-I) axis were
      evaluated in female rhesus monkeys to test the hypothesis that estradiol
      differentially regulates IGF-I secretion and molar ratios of IGF-I to IGF-binding
      protein-3 (IGFBP-3) from adolescence into adulthood and that estradiol can
      reestablish GH secretion in the face of enhanced IGF-I negative feedback
      inhibition of GH. Adult ovariectomized females were compared to ovariectomized
      adolescent females studied from 18-36 months of age, a period encompassing the
      juvenile phase through the expected age at first ovulation. A subgroup of adult
      (n = 5) and adolescent females (n = 5) was treated continuously with human IGF-I
      (110 micrograms/kg.day, s.c.) throughout the study period and were compared to
      age-matched, untreated adults (n = 5) and adolescent animals (n = 6). To further
      understand how IGF-I affects the GH-IGF-I axis, the acute response to IGF-I (100
      micrograms/kg, s.c.) was assessed in adults and at two ages in developing
      females. Furthermore, all females were treated periodically with estradiol (4
      micrograms/kg.day) to assess the effects on the parameters of the GH-IGF-I axis
      from adolescence into adulthood. Finally, the response to GHRH (1.0 microgram/kg,
      i.v.) was assessed in adult females and in adolescent females at 18 and 24 months
      during no estradiol and estradiol replacement. Serum IGF-I and IGFBP-3, in the
      absence of estradiol replacement, increased significantly throughout puberty
      before declining from late adolescence into adulthood. Supplementation with IGF-I
      resulted in a significant increase in both serum IGF-I and IGFBP-3 concentrations
      at all ages, although the effect was less in juvenile females. Nevertheless, the
      age-dependent increase and decline in IGF-I and IGFBP-3 were maintained in these
      supplemented animals. Estradiol replacement significantly increased both serum
      IGF-I and IGFBP-3 through adolescence, even in IGF-I-supplemented animals.
      However, with the transition from adolescence, estradiol suppressed serum IGF-I
      secretion, yet continued to increase IGFBP-3 in young adult and fully adult
      females. This change in proportionately less IGF-I compared with IGFBP-3 resulted
      in a significant age-dependent decrease in the molar ratio of IGF-I to IGFBP-3.
      Indeed, the molar ratio was highest during midadolescence, when both IGF-I and
      IGFBP-3 were at their zeniths. Serum IGFBP-1 was significantly higher in
      adolescent compared with adult females. However, estradiol replacement
      significantly elevated serum IGFBP-1 in adult, but not adolescent, females,
      abolishing the age differences observed under no estradiol conditions. Serum GH
      was significantly higher in adolescent compared with adult females; levels in
      juvenile animals were intermediate. Replacement with estradiol significantly
      elevated serum GH in adolescent and adult females, particularly in females
      supplemented with IGF-I. In contrast, estradiol had no effect on serum GH during
      the juvenile phase. Supplementation with IGF-I significantly dampened the
      response to GHRH in young and fully adult females, but not in juvenile animals.
      However, estradiol replacement restored the response to GHRH in these adult, IGF
      I-supplemented females. These data indicate that in the absence of any ovarian
      influence, the decline in serum IGF-I and IGFBP-3 begins in postpubertal, young
      adult females and is not necessarily a consequence of old age. Furthermore, there
      is an age-dependent uncoupling of estradiol regulation of the GH-IGF-I axis, as
      estradiol stimulates GH and IGFBP-3 at all ages but increases serum IGF-I only
      during adolescent and decreases IGF-I in postpubertal, young adult females.
      Furthermore, IGF-I has a greater suppressive effect on GH secretion with
      advancing age, an effect reversed by estradiol replacement. These data suggest
      that the deficits in the GH-IGF-I axis observed in aged individuals may reflect a
      continuation of the regulatory changes that begin in young adult females.

PMID- 9626135
TI  - Variable expression of the V1 vasopressin receptor modulates the phenotypic
      response of steroid-secreting adrenocortical tumors.
AB  - We studied the putative role of the vasopressin receptors in the phenotypic
      response of steroid-secreting adrenocortical tumors. A retrospective analysis of
      a series of 26 adrenocortical tumors responsible for Cushing's syndrome (19
      adenomas and 7 carcinomas) showed that vasopressin (10 IU, i.m., lysine
      vasopressin) induced an ACTH-independent cortisol response (arbitrarily defined
      as a cortisol rise above baseline of 30 ng/mL or more) in 7 cases (27%). In
      comparison, 68 of 90 patients with Cushing's disease (76%) had a positive
      cortisol response. We then prospectively examined the expression of vasopressin
      receptor genes in adrenocortical tumors of recently operated patients (20
      adenomas and 19 adrenocortical carcinomas). We used highly sensitive and specific
      quantitative RT-PCR techniques for each of the newly characterized human
      vasopressin receptors: V1, V2, and V3. The V1 messenger ribonucleic acid (mRNA)
      was detected in normal adrenal cortex and in all tumors. Its level varied widely
      between 2.0 x 10(2) and 4.4 x 10(5) copies/0.1 microgram total RNA, and adenomas
      had significantly higher levels than carcinomas, although there was a large
      overlap. Among the 6 recently operated patients who had been subjected to the
      vasopressin test in vivo, the tumor V1 mRNA levels were higher in the 4
      responders (9.5 x 10(3) to 5.0 x 10(4)) than in the 2 nonresponders (2.0 x 10(2)
      and 1.8 x 10(3)). One adenoma that had a brisk cortisol response in vivo, also
      had in vitro cortisol responses that were inhibited by a specific V1 antagonist.
      In situ hybridization showed the presence of V1 mRNA in the normal human adrenal
      cortex where the signal predominated in the compact cells of the zona
      reticularis. A positive signal was also present in the tumors with high RT-PCR V1
      mRNA levels; its distribution pattern was heterogeneous and showed preferential
      association with compact cells. RT-PCR studies for the other vasopressin
      receptors showed a much lower signal for V2 and no evidence for V3 mRNA. We could
      not establish whether the V2 mRNA signal observed in normal and tumoral specimens
      was present within adrenocortical cells or merely within tissue vessels. We
      conclude that the vasopressin V1 receptor gene is expressed in normal and tumoral
      adrenocortical cells. High, and not ectopic, expression occurs in a minority of
      tumors that become directly responsive to vasopressin stimulation tests.

PMID- 9626136
TI  - Polymerase chain reaction-based microsatellite polymorphism analysis of
      follicular and Hurthle cell neoplasms of the thyroid.
AB  - Follicular and Hurthle cell carcinomas of the thyroid cannot be differentiated
      from adenomas by either preoperative fine needle aspiration or intraoperative
      frozen section examination, and yet there exist potentially significant
      differences in the recommended surgical management. We examined, by PCR-based
      microsatellite polymorphism analysis, DNA obtained from 83 thyroid neoplasms [22
      follicular adenomas, 29 follicular carcinomas, 20 Hurthle cell adenomas (HA), and
      12 Hurthle cell carcinomas (HC)] to determine whether a pattern of allelic
      alteration exists that could help distinguish benign from malignant lesions.
      Alterations were found in only 7.5% of informative PCR reactions from follicular
      neoplasms, whereas they were found in 23.3% of reactions from Hurthle cell
      neoplasms. Although there were no significant differences between follicular
      adenoma and follicular carcinoma, HC demonstrated a significantly greater
      percentage of allelic alteration than HA on chromosomal arms 1q (P < 0.001) and
      2p (P < 0.05) by Fisher's exact test. The documentation of an alteration on
      either 1q or 2p was 100% sensitive and 65% specific in the detection of HC (P <
      0.0005, by McNemar's test). In conclusion, PCR-based microsatellite polymorphism
      analysis may be a useful technique in distinguishing HC from HA. Potentially, the
      application of this technique to aspirated material may allow this distinction
      preoperatively and thus facilitate more optimal surgical management. Consistent
      regions of allelic alteration may also indicate the locations of critical genes,
      such as tumor suppressor genes or oncogenes, that are important in the
      progression from adenoma to carcinoma. Finally, this study demonstrates that
      Hurthle cell neoplasms, now considered variants of follicular neoplasms, differ
      significantly from follicular neoplasms on a molecular level.

PMID- 9626137
TI  - In vitro secretion of cytokines by human bone marrow: effects of age and estrogen
      status.
AB  - It has been proposed that cytokines mediate the acceleration of bone loss
      following menopause. Because of the intimate relationship between bone marrow
      stromal cells and bone tissue, it is possible that marrow cells and their
      products contribute to the bone microenvironment and influence the regulation of
      bone cell differentiation and activity. We examined the production of cytokines
      by bone marrow stromal cells from a total of 37 women and 15 men undergoing total
      hip replacement for noninflammatory joint disease. Low-density mononuclear cells
      were isolated from bone marrow and were cultured in phenol red-free alpha MEM
      medium supplemented with 10% FBS and antibiotics. Constitutive secretion of
      interleukin-6 (IL-6) was positively correlated with age in a series of 8 women
      and 5 men measured by bioassay (r = 0.98; P < 0.01) and in a series of 18 women
      and 10 men measured by immunoassay (r = 0.56; P < 0.01). The pattern of cytokine
      production by bone marrow stromal cells was examined in detail in 23
      postmenopausal women, aged 49-88 yr. Basal secretion of immunoreactive IL-6 and
      IL-11, but not granulocyte-macrophage colony-stimulating factor, increased with
      time in culture. Exogenous IL-1 beta stimulated secretion of IL-6 and IL-11 in a
      saturable, dose-dependent manner. Secretion of soluble IL-6 receptor was not
      correlated with secretion of IL-6, either constitutively or in the presence of IL
      1 beta. In 4 of 14 samples, IL-1 beta also stimulated secretion of granulocyte
      macrophage colony-stimulating factor. IL-1 beta was undetectable in 7 of 9
      cultures during the 2-week culture period. IL-6 did not stimulate secretion of IL
      1 beta in the 7 cultures tested. Cells were dependent upon serum for viability
      and growth and were not sustained by a serum substitute (1% insulin-transferrin
      selenium-BSA). Cells grown in medium with 10% FBS and supplemented with 1%
      insulin-transferrin-selenium-BSA secreted 10-fold more IL-6 than cells grown in
      serum alone. Marrow from 7 women receiving estrogen replacement therapy showed
      lower constitutive secretion of IL-6 (75%; P < 0.006) and IL-11 (43%; P < 0.05)
      than marrow from age-matched controls and had blunted stimulation of IL-6 and IL
      11 secretion by exogenous IL-1 beta. These data indicate distinct patterns of
      cytokine production by human marrow stromal cultures dependent upon age and
      estrogen status.

PMID- 9626138
TI  - Identification of a 57-kilodalton selenoprotein in human thyrocytes as
      thioredoxin reductase and evidence that its expression is regulated through the
      calcium-phosphoinositol signaling pathway.
AB  - Human thyrocytes incubated with the phorbol ester, phorbol 12-myristate 13
      acetate (PMA; 10(-5)-10(-8) mol/L) and the calcium ionophore A23187 (10(-5)-10(
      8) mol/L) showed a marked increase in the expression of a 57-kDa selenoprotein
      identified as thioredoxin reductase (TR). After the addition of A23187 with PMA,
      a significant induction in TR expression was observed after 6 h, with maximal
      induction occurring by 24 h. The addition of 8-bromo-cAMP (10(-4) mol/L) or TSH
      (10 U/L) alone had no effect on TR expression, nor did these agents influence the
      induction of TR brought about by the addition of A23187 and PMA. These data show
      that the calcium-phosphoinositol second messenger cascade that controls hydrogen
      peroxide generation in the human thyrocyte is also an important stimulator of TR
      expression. The role of TR in the thyrocyte is unclear, but the selenoenzyme has
      a high capacity to detoxify compounds, such as hydrogen peroxide and lipid
      hydroperoxides, that are produced in high concentration during thyroid hormone
      synthesis.

PMID- 9626139
TI  - Linkage and molecular scanning analyses of MODY3/hepatocyte nuclear factor-1
      alpha gene in typical familial type 2 diabetes: evidence for novel mutations in
      exons 8 and 10.
AB  - Mutations of the hepatocyte nuclear factor-1 alpha (HNF1 alpha) gene are an
      important cause of autosomal dominant diabetes with onset before age 25 yr
      [maturity-onset diabetes of the young (MODY)], and some regions of the HNF1 alpha
      gene appear to be hot spots for mutations. To evaluate the role of HNF1 alpha in
      the more common familial type 2 diabetes, we studied 62 families of Northern
      European origin by linkage analysis and molecular screening. Linkage was rejected
      under dominant models consistent with either late-onset type 2 diabetes or early
      onset dominant diabetes. We used single strand conformation polymorphism analysis
      to screen 53 diabetic members of 36 families who reported diabetes diagnosed
      before age 40 yr, 9 members of 2 Utah families with typical MODY, and 24
      additional members of families with possible linkage. One MODY family showed the
      previously reported frameshift mutation (P291fsinsC) in exon 4. Among the
      individuals with more typical type 2 diabetes, we identified the previously
      reported common polymorphisms, a new intronic polymorphism, and 3 common amino
      acid variants. We also identified 2 novel missense mutations that segregated with
      type 2 diabetes in 1 family each: lysine for glutamic acid substitution at codon
      619 in exon 10 (E619K), and an arginine for threonine substitution at codon 537
      in exon 8 (R537T) in a second family. The exon 8 mutation showed relatively low
      penetrance, and the role in this family remains uncertain. No coding mutations
      were identified in the family members screened on the basis of linkage but
      without early-onset diabetes. Although HNF1 alpha mutations are not a common
      cause of familial type 2 diabetes, they may account for 5% of families in which
      at least 1 member has onset of type 2 diabetes before age 40 yr. Incomplete
      penetrance and a high sporadic frequency make linkage an inefficient screening
      tool.

PMID- 9626140
TI  - Glucocorticoids suppress corticotropin-releasing hormone and vasopressin
      expression in human hypothalamic neurons.
AB  - Glucocorticoids are widely used in clinical practice in a variety of immune
      mediated and neoplastic diseases, mostly for their immunosuppressive, leukopenic,
      antiedematous, or malignancy-suppressive actions. However, their usage is limited
      because of serious and sometimes life-threatening side-effects. Endogenous
      glucocorticoids are secreted by the adrenal cortex under the control of the
      hypothalamus and the pituitary gland. This hypothalamo-pituitary-adrenal axis, in
      turn, is under the negative feedback control of glucocorticoids. Although the
      suppression of adrenocortical and pituitary gland functions by glucocorticoids
      has been shown in humans, a feedback effect at the level of the hypothalamus, as
      shown in rat, has not been reported to date. The present study shows for the
      first time that glucocorticoids suppress both CRH and vasopressin (AVP) in the
      human hypothalamus. We studied immunocytochemically the postmortem hypothalami of
      nine corticosteroid-exposed subjects and eight controls. The number of CRH
      expressing cells in the hypothalamic paraventricular nucleus of glucocorticoid
      exposed patients was only 3.3% of that in the controls, and the total
      immunoreactivities for AVP were 31% and 33% of that in the controls in the
      supraoptic nucleus and the paraventricular nucleus, respectively, whereas the
      immunoreactivity for oxytocin did not differ between the two groups. Suppression
      of hypothalamic CRH and AVP neurons by glucocorticoids may have important
      consequences for neuroendocrinological mechanisms such as the disturbance of
      water balance during the treatment as well as the immunological processes in the
      brain and the pathogenesis of the withdrawal syndrome after discontinuation of
      corticosteroid treatment. In addition, as both AVP and CRH neurons also project
      to other brain structures and influence memory, mood, and behavior, their
      suppression by glucocorticoids may be responsible for at least part of the
      central nervous system side-effects of glucocorticoids.

PMID- 9626141
TI  - Activating mutation of the stimulatory G protein (gsp) as a putative cause of
      ovarian and testicular human stromal Leydig cell tumors.
AB  - Activating mutations of the G protein genes have been associated with the
      development of several endocrine neoplasms. Such activating mutations, gip2,
      affecting the alpha-subunit of the G alpha i2 protein were previously described
      by a single group in 30% of ovarian sex cord stromal tumors. Other activating
      mutations of the alpha-subunit of the Gs (gsp) have been identified in GH
      secreting and nonfunctioning pituitary tumors, autonomous thyroid adenomas, and
      all affected McCune-Albright tissues, but not in sex cord stromal tumors. In the
      present study, we investigated the presence of gip2 and gsp mutations in 14 human
      sex cord stromal tumors. Six Leydig cell tumors (4 ovaries and 2 testes), 2
      thecomas, 2 granulosa cell tumors, 3 androblastomas, and 1 gonadoblastoma (sex
      cord and germ cell) were included in this study. Genomic DNA was obtained from
      either fresh-frozen tumor tissues or paraffin-embedded sections and in some cases
      from blood samples. Using PCR, denaturing gradient gel electrophoresis, and
      direct sequencing, we detected 4 tumors (66.6%) with the gsp mutation (R201C) in
      our series of ovarian and testicular Leydig cell tumors. In contrast, no gip2
      mutations were found in any of the sex cord stromal tumors studied. In
      conclusion, our findings suggest that the putative oncogene gsp may play a
      significant role in the molecular mechanism of these tumors.

PMID- 9626142
TI  - Pro239Ser: a novel recessive mutation of the Pit-1 gene in seven Middle Eastern
      children with growth hormone, prolactin, and thyrotropin deficiency.
AB  - Pit-1, a member of the POU-homeo domain protein family, is one of the
      transcription factors responsible for anterior pituitary development and
      pituitary-specific gene expression. Here, we describe seven children with GH,
      PRL, and TSH deficiency from three, reportedly unrelated, Middle Eastern
      families, harboring a newly recognized Pro- > Ser recessive mutation in codon 239
      of the Pit-1 gene. The mutated residue is located at the beginning of the second
      alpha-helix of the POU-homeodomain and is strictly conserved among all POU
      proteins. The Pro239Ser mutant binds DNA normally but is unable to stimulate
      transcription.

PMID- 9626143
TI  - Autonomic and hemodynamic responses to insulin in lean and obese humans.
AB  - To study the acute effects of insulin on autonomic control of cardiac function,
      we performed spectral analysis of heart rate variability and measured cardiac
      dynamics (by two-dimensional echocardiography) in 18 obese (BMI = 35 +/- 1 kg.m
      2) and 14 lean (BMI = 24 +/- 1 kg.m-2) subjects in the basal state and in
      response to physiological hyperinsulinemia (1 mU.min-1.kg-1 insulin clamp). In
      the lean group, insulin promptly (within 20 min) and consistently depressed
      spectral powers, both in the low-frequency and high-frequency range. These
      changes were twice as large as accounted for by the concomitant changes in heart
      rate (68 +/- 2 to 70 +/- 2 beats/min). At the end of the 2-h clamp, stroke volume
      (67 +/- 4 to 76 +/- 9 ml.min-1) and cardiac output (4.45 +/- 0.21 to 5.06 +/-
      0.55 l.min-1) rose, whereas peripheral vascular resistance fell. The low-to-high
      frequency ratio increased from 1.7 +/- 0.2 to 2.3 +/- 0.3 (P < 0.01), indicating
      sympathetic shift of autonomic balance. In the obese group, all basal spectral
      powers were significantly lower (by 40% on average) than in the lean group, and
      were further reduced by insulin administration. The low-to-high frequency ratio
      was higher than in controls at baseline (2.4 +/- 0.4, P < 0.03), and failed to
      increase after insulin (2.2 +/- 0.3, P = ns). Furthermore, obesity was associated
      with higher resting stroke volume (89 +/- 5 vs. 67 +/- 4 ml.min-1, P < 0.01) and
      cardiac output (6.01 +/- 0.31 vs. 4.45 +/- 0.21 l.min-1, P = 0.001) but lower
      peripheral vascular resistance (15.1 +/- 0.8 vs. 19.2 +/- 1.1 mmHg.min.L-1, P =
      0.002), whereas mean arterial blood pressure was similar to control (90 +/- 2 vs.
      86 +/- 2 mmHg, P = not significant). We conclude that physiological
      hyperinsulinemia causes acute desensitization of sinus node activity to both
      sympathetic and para-sympathetic stimuli, sympathetic shift of autonomic balance,
      and a high-output, low-resistance hemodynamic state. In the obese, these changes
      are already present in the basal state, and may therefore be linked with chronic
      hyperinsulinemia.

PMID- 9626144
TI  - A novel mutation of the human luteinizing hormone receptor in 46XY and 46XX
      sisters.
AB  - We report a novel homozygous mutation of the LH receptor (LHR) gene in three
      siblings: two 46XY and one 46XX. The 46XY siblings presented with female external
      genitalia, primary amenorrhea, and lack of breast development. Hormonal
      evaluation revealed a markedly elevated LH level with a low testosterone level,
      which failed to increase after human CG stimulation. Enzymatic deficiencies of
      testosterone biosynthesis were eliminated as possible etiologies. Histologic
      analysis of the inguinal gonads in a 46XY sibling revealed no Leydig cells;
      Sertoli cells, spermatogonia, and primary spermatocytes were seen. The 46XX
      sibling had female external genitalia, normal breast development, and primary
      amenorrhea. Hormonal analyses showed markedly elevated LH levels and low plasma
      17 beta-estradiol levels. Genetic analysis of the LHR revealed a homozygous
      missense mutation at exon 11 of the LHR gene. Guanine was replaced by adenine
      (GAA-->AAA), resulting in a substitution of lysine for glutamic acid (glu) at
      amino acid position 354 of the receptor. This mutation is located in the
      extracellular domain adjacent to the first transmembrane helix of the LHR.
      Glutamic acid at position 354 of the LHR has been highly conserved throughout
      evolution. Functional analysis of the LHR mutation, using an in vitro mutagenesis
      transfection assay, demonstrated complete loss of function, indicated by the lack
      of cAMP production after human CG stimulation in transfected human embryonic
      kidney 293 cells. Screening of family members demonstrated heterozygosity for the
      mutation, indicating autosomal recessive inheritance. Delineation of the specific
      genetic defect in this family confirms recent reports that a single mutation in
      the LHR gene causes male pseudohermaphroditism in 46XY subjects and primary
      amenorrhea in 46XX subjects. More importantly, it also defines a new region of
      the LHR molecule that is critical for biologic activity.

PMID- 9626145
TI  - Circulating levels of allopregnanolone in humans: gender, age, and endocrine
      influences.
AB  - Allopregnanolone is a neuroactive steroid involved in modulating behavioral
      functions, stress, and neuroendocrine axes in rats. Changes in plasma
      allopregnanolone levels throughout the menstrual cycle have been reported in
      healthy women, but there exists no information on the possible gender or age
      related changes or on the source(s) of circulating allopregnanolone. The aim of
      the present study was to assess serum allopregnanolone concentrations according
      to gender, menstrual cycle, age, and menopause in normal men and women; serum
      progesterone (P) and dehydroepiandrosterone (DHEA) levels were evaluated in the
      same specimens. In addition, the possible source of circulating allopregnanolone
      in fertile women was investigated by using stimulatory and inhibitory endocrine
      tests acting on the ovary and/or adrenal cortex. The present study included 189
      fertile women, 112 postmenopausal women, and 46 men. Serum steroid levels were
      determined after extraction, using specific RIAs. Allopregnanolone levels in
      fertile women in the follicular phase were similar to those in age-matched men;
      no significant difference was found between fertile women in the follicular phase
      and postmenopausal women. The highest levels were found in fertile women during
      the luteal phase (P < 0.01). An age-related decrease was observed in men (P <
      0.01), but not in women. P and DHEA levels were significantly higher in women
      than in men and were higher in fertile women than in postmenopausal women (P <
      0.01). Both P and DHEA showed an age-related decrease in men and women (P <
      0.01). Serum allopregnanolone and P, but not DHEA, significantly increased in
      response to a GnRH test, whereas corticotropin-releasing factor and ACTH tests
      elicited a significant increase in allopregnanolone, P, and DHEA levels (P <
      0.01). The suppression of adrenal steroidogenesis by dexamethasone markedly
      reduced both allopregnanolone and DHEA serum levels (P < 0.01). In conclusion,
      the present study demonstrated that although men show an age-related decrease,
      serum allopregnanolone levels in women do not change with age and correlate with
      P levels during the menstrual cycle and in response to endocrine tests. Ovary and
      adrenal cortex may be major sources of circulating allopregnanolone in fertile
      women.

PMID- 9626146
TI  - Comparative rates of androgen production and metabolism in Caucasian and Chinese
      subjects.
AB  - Clinically apparent prostate cancer occurs more commonly among Caucasians living
      in Western countries than in Chinese in the Far East. Prior studies demonstrated
      diminished facial and body hair and lower levels of plasma 3 alpha-androstanediol
      glucuronide and androsterone glucuronide in Chinese than in Caucasian men. Based
      upon these findings, investigators postulated that Chinese men could have
      diminished 5 alpha-reductase activity with a resultant decrease in prostate
      tissue dihydrotestosterone levels and clinically apparent prostate cancer. An
      alternative hypothesis suggests that decreased 3 alpha-androstanediol glucuronide
      and androsterone glucuronide levels might reflect reduced production of
      androgenic ketosteroid precursors as a result of genetic or environmental
      factors. The present study examined 5 alpha-reductase activity, androgenic
      ketosteroid precursors, and the influence of genetic and environmental/dietary
      factors in groups of Chinese and Caucasian men. We found no significant
      differences in the ratios of 5 beta-:5 alpha-reduced urinary steroids (a marker
      of 5 alpha-reductase activity) between Chinese subjects living in Beijing, China,
      and Caucasians living in Pennsylvania. To enhance the sensitivity of detection,
      we used an isotopic kinetic method to directly measure 5 alpha-reductase activity
      and found no difference in testosterone to dihydrotestosterone conversion ratios
      between groups. Then, addressing the alternative hypothesis, we found that the
      Caucasian subjects excreted significantly higher levels of individual and total
      androgenic ketosteroids than did their Chinese counterparts. To distinguish
      genetic from environmental/dietary factors as a cause of these differences, we
      compared Chinese men living in Pennsylvania and a similar group living in
      Beijing, China. We detected a reduction in testosterone production rates and
      total plasma testosterone and sex hormone-binding levels, but not in testosterone
      MCRs in Beijing Chinese as a opposed to those living in Pennsylvania. Comparing
      Pennsylvania Chinese with their Caucasian counterparts, we detected no
      significant differences in total testosterone, free and weakly bound
      testosterone, sex hormone-binding globulin levels, and testosterone production
      rates. Taken together, these studies suggest that environmental/dietary, but not
      genetic, factors influence androgen production and explain the differences
      between Caucasian and Chinese men.

PMID- 9626147
TI  - Lysophosphatidyl choline, a chemotactic factor for monocytes/T-lymphocytes is
      elevated in endometriosis.
AB  - Inflammatory processes have been hypothesized to mediate some of the clinical
      sequelae associated with endometriosis. The peritoneal fluid (PF) of women with
      endometriosis is known to contain more inflammatory cells and their associated
      cytokines, chemokines, and growth factors. This work provides strong evidence for
      oxidative stress in the PF of women with endometriosis. 1) The low density
      lipoprotein (LDL) isolated from the PF of subjects with endometriosis shows a
      small but detectable increase in electrophoretic mobility compatible with mildly
      oxidized LDL compared with LDL isolated from the plasma of the same subjects and
      PF of controls. 2) Isolated PF-LDL of endometriosis subjects is more readily
      oxidized in vitro than PF-LDL of controls, or LDL isolated from plasma. 3)
      Vitamin E content is significantly lower in endometriosis PF compared with
      controls, and compared with plasma of women with endometriosis and controls. No
      difference is seen between plasma and PF of control subjects. 4) The ratio of
      phosphatidylcholine/lyso phosphatidylcholine (Ptd/lyso PtdCho) in the PF of
      endometriosis subjects is significantly lower compared with PF of controls. Taken
      together, these data provide strong evidence for a pro-oxidant environment in the
      peritoneal cavity of women with endometriosis. Lyso PtdCho, a product derived
      from phospholipase A2 action on peroxidized phosphatidylcholine and a potent
      chemotactic factor for monocytes and T-lymphocytes, is elevated in endometriosis.
      We hypothesize that the increased presence of lipid peroxidation products in the
      PF of endometriosis subjects may, at least partly, account for the recruitment of
      leukocytes, the increase in macrophage activation, the secretion of monocyte-
      macrophage-derived cytokines, and the endometrial growth-promoting activity
      associated with endometriosis.

PMID- 9626148
TI  - Familial isolated hyperparathyroidism maps to the hyperparathyroidism-jaw tumor
      locus in 1q21-q32 in a subset of families.
AB  - Approximately 70 families with familial isolated hyperparathyroidism (FIHP) have
      been reported. Whether it is a separate entity or a variant of multiple endocrine
      neoplasia type 1 (MEN1 at 11q13) or hyperparathyroidism-jaw tumor (HPT-JT or
      HRPT2 at 1q21-32) syndrome is not known. We describe here 3 unreported families
      with familial primary hyperparathyroidism and evaluate their clinical,
      pathological, and genetic profiles. Biochemical and radiological screenings for
      MEN1 were negative for all families. In 2 families with a total of 10 affected
      cases and 3 female obligate carriers, there is no evidence of jaw or renal
      lesions despite careful radiological investigations. In both families the disease
      was linked to the 1q21-q32 region with the maximum logarithm of the odds (lod)
      scores of 3.10 and 3.43 for markers D1S222 and D1S249 respectively, at
      recombination fraction of 0. In 1 family 2 types of parathyroid pathology were
      found: 3 of chief cell type and 1 of oxyphil/oncocytic cell type. Two chief cell
      tumors and 1 oxyphil tumor were found to have loss of heterozygosity (LOH)
      involving loss of the wild-type alleles for chromosome 1q markers. In the third
      family, with 4 affected siblings, a parathyroid carcinoma and 2 cases of
      polycystic kidney disease were found. The parathyroid carcinoma also showed loss
      of heterozygosity in the 1q region. In conclusion, we found that the
      hyperparathyroidism traits in a subset of FIHP families are linked to the 1q21-32
      markers in the HRPT2 region. We describe the spectrum of parathyroid disease in
      1q-linked families involving 3 different types of pathology and demonstrate for
      the first time loss of wild-type alleles in these parathyroid tumors. Taken
      together, the results suggest that some of the FIHP are a variant of HPT-JT and
      that the gene involved is a tumor suppressor gene.

PMID- 9626149
TI  - Reversibility of joint thickening in acromegalic patients: an ultrasonography
      study.
AB  - Axial and peripheral arthropathy affects the majority of patients with
      acromegaly, being a leading cause of morbidity and functional disability.
      Treatment with octreotide (OCT) improves symptoms and signs of acromegalic
      arthropathy, but objective detection of structural changes in bone and cartilage
      has not been reported to date. This open prospective study was designed to
      evaluate the effect of a long term treatment with OCT on acromegalic arthropathy
      assessed by ultrasonography examination. Articular cartilage thicknesses of
      shoulder, wrist, and knee as well as sizes of heel tendons were measured in 30
      acromegalic patients (18 with active and 12 with inactive disease) and 18 sex-,
      age-, and body mass index-matched healthy subjects. The thicknesses of shoulder,
      wrists and knees articular cartilages and that of heel tendons were significantly
      increased in patients with active acromegaly compared to those in healthy
      subjects (P < 0.01). With the exception of shoulder cartilage, significant
      increases in wrist and knee cartilages (P < 0.01) and right and left heel tendon
      sizes (P < 0.05) were found in patients with active compared to those with
      inactive disease. After 6 months of OCT treatment, a significant decrease in
      shoulder, wrist, and left knee articular cartilage was found (P < 0.001). No
      significant change was recorded in right knee cartilage or heel tendon size. The
      decrease in thickness of shoulder and wrist cartilages was more pronounced than
      that measured at the level of left knee (26.3 +/- 3.3% and 27.2 +/- 4.2% vs. 14.2
      +/- 4.2%, respectively; P < 0.05). Ultrasonography is able to reveal articular
      involvement in acromegalic patients and may be useful to monitor the effect of
      treatment.

PMID- 9626150
TI  - The vasodilating effect of insulin is dependent on local glucose uptake: a double
      blind, placebo-controlled study.
AB  - During systemic hyperinsulinemia in man, skeletal muscle vasodilation has
      consistently been demonstrated. However, most studies that have examined the
      vascular effect of local hyperinsulinemia have reported either no effect or only
      weak vasodilation, and all of these have been open in design. The present studies
      were designed in a double blind, placebo-controlled manner to evaluate the direct
      (local) vascular effect of insulin alone and in association with physiological
      concentrations of D-glucose. Forearm blood flow was measured in 17 healthy male
      volunteers by bilateral venous occlusion forearm plethysmography. Brachial artery
      infusions of 1 mU/min insulin, 5 mU/min insulin, or vehicle were administered for
      90 min on 3 separate study days in random order. The higher dose of insulin was
      associated with weak (20%) vasodilation compared with placebo (F = 5.75 and P <
      0.01, by ANOVA). When this protocol was repeated with intraarterial coinfusion of
      D-glucose, significant augmentation of the vascular effect was demonstrated (47%
      vasodilation). No augmentation of insulin-mediated vasodilation was observed with
      coinfusion of L-glucose, the metabolically inactive stereoisomer. These data
      suggest that local uptake of D-glucose by insulin-sensitive tissues is an
      important determinant of insulin-mediated vasodilation.

PMID- 9626151
TI  - Short-term impact of a lactovegetarian diet on adrenocortical activity and
      adrenal androgens.
AB  - The aim of this study was to determine whether definite diet changes affect
      adrenocortical activity and/or adrenal androgen metabolism. A controlled
      experimental diet study with four consecutive diet periods (repeated measure
      design) was carried out in six healthy adult volunteers. Four nearly isoenergetic
      diets, two normal (N) moderately protein-rich, one protein-rich (P), and one low
      protein lactovegetarian (L), were fed. At the end of each 5-day diet period a
      blood sample and two 24-h urine specimens were obtained from each subject. Plasma
      levels of dehydroepiandrosterone sulfate (DHEAS) were elevated with diet L (6.5
      +/- 1.4 vs. 5.3 +/- 1.1 mumol/L; P < 0.05) compared to diet N, whereas other
      plasma hormones, including cortisol and insulin-like growth factor I did not vary
      markedly. A marked increase of 60% was seen in the urinary 24-h output of 3 alpha
      androstanediol glucuronide with diet P. Urinary 24-h excretion rates for C
      peptide, free cortisol, DHEAS, and total 17-ketosteroid sulfates were clearly
      reduced with diet L compared to those with diet N or P. Our results show that a
      lactovegetarian diet can reduce adrenocortical activity (at least after a short
      term diet change). In addition, this vegetarian nutrition leads to a particular
      metabolic situation (elevated plasma DHEAS and reduced urinary DHEAS output) that
      usually is characteristic of fasting. Peripheral androgen metabolism as reflected
      by urinary 3 alpha-androstanediol glucuronide appears to be influenced only by
      high protein intake (diet P). Further research (controlled dietary long term
      investigation) is required 1) to validate whether the effects of diet on
      adrenocortical activity represent sustained endocrine changes and 2) to elucidate
      the underlying mechanism.

PMID- 9626152
TI  - Relationship between plasma adrenocorticotropin, hypothalamic opioid tone, and
      plasma leptin.
AB  - The purpose of the present study was to further the understanding of the
      relationship between plasma leptin concentrations, hypothalamic opioid tone, and
      plasma ACTH secretory dynamics. ACTH(1-24) challenges (250 micrograms) produced
      the expected increase in plasma cortisol levels but did not alter plasma leptin
      levels. Activation of the entire hypothalamic-pituitary-adrenal (HPA) axis was
      induced by employing the opioid receptor antagonist, naloxone. By blocking
      opioidergic inhibitory input to hypothalamic CRH neurons, naloxone induced the
      expected increase in plasma ACTH and cortisol. Plasma ACTH levels peaked 30 min
      after naloxone administration, whereas plasma cortisol levels peaked 60 min after
      opioid receptor blockade. Once again, plasma leptin concentrations were not
      altered by this manipulation. However, there was a positive correlation between
      fasting, integrated plasma leptin concentrations, and plasma ACTH responses to
      naloxone (peak r = 0.822, P < 0.0001; and area under curve r = 0.832, P <
      0.0001). The correlation was stronger when leptin was normalized to body mass
      index and expressed as the leptin/body mass index ratio (peak r = 0.878, P <
      0.00001; and area under curve r = 0.882, P < 0.00001). In summary, these findings
      indicate that activation of the HPA axis does not acutely alter plasma leptin
      concentrations. However, plasma leptin levels may influence hypothalamic
      opioidergic tone and thus modulate the magnitude of CRH release. The acute
      interaction of the HPA axis and leptin is unidirectional.

PMID- 9626153
TI  - Skeletal effects of two years of treatment with low physiological doses of
      recombinant human growth hormone (GH) in patients with adult-onset GH deficiency.
AB  - A low bone mass in adults with childhood-onset GH deficiency (GHD) is likely to
      be caused by deficient bone accretion during childhood and early adulthood,
      whereas a decreased bone mass in patients with adult-onset GHD is likely to be
      caused by an imbalance in bone remodeling. Data on bone mineral density (BMD) and
      biochemical parameters of bone metabolism and data on response of these
      parameters to treatment with GH are scarce in patients with adult-onset GHD. It
      has been suggested that in patients with GHD, GH at the relatively high dose
      originally used may have beneficial effects on the skeleton. To address the
      question as whether lower, more physiological doses would have similar effects on
      the skeleton, we studied 47 patients with adult-onset GHD (27 women and 20 men,
      range 26-70 yr) randomized to receive one of three recombinant human GH (rhGH)
      dose regimens: 0.6 IU/day, 1.2 IU/day, or 1.8 IU/day as part of a study examining
      optimal GH dose replacement therapy. After 24 weeks of treatment, the dose of
      rhGH was individually adjusted to maintain the concentration of serum insulin
      growth factor-I within the normal laboratory reference range. Biochemical
      parameters of bone metabolism were measured at baseline and after 24 and 52 weeks
      and 2 yr of treatment. BMD of the lumbar spine was measured at baseline and after
      52 weeks and 2 yr of treatment. Parameters of bone metabolism generally fell
      within the low-normal range and increased in a dose-dependent manner at 24 weeks
      of treatment. Between 24 and 52 weeks of rhGH treatment, mean serum osteocalcin
      levels and alkaline phosphatase activity further increased, whereas mean 24-h
      urine hydroxyproline/creatinine and N-telopeptide/creatinine excretion remained
      unchanged. After 52 weeks of treatment, serum alkaline phosphatase activity and
      24-h urine hydroxyproline/ creatinine excretion decreased, although not to
      pretreatment levels. Mean BMD at the lumbar spine (Z-score) was normal at
      baseline (-0.20 +/- 0.16) and increased during treatment (at 2 yr of treatment: 0
      +/- 0.20; P < 0.005). Our data suggest that a low physiological dose of rhGH,
      individually adjusted to maintain serum insulin-like growth factor I levels
      within the normal laboratory reference range, increased bone turnover in favor of
      bone formation, as suggested by the significant, albeit small increase in BMD
      observed after 2 yr of treatment. Further studies are required to establish
      whether in patients with adult-onset GHD the preservation and/or increase in bone
      mass observed with the use of physiological doses of rhGH could be maintained
      with longer-term treatment.

PMID- 9626154
TI  - Gender differences in both spontaneous and stimulated leptin secretion by human
      omental adipose tissue in vitro: dexamethasone and estradiol stimulate leptin
      release in women, but not in men.
AB  - Leptin is a hormone secreted by the adipocytes to serve as a signal to the
      central nervous system to regulate energy homeostasis. Circulating leptin mainly
      reflects both total fat mass and the size of constituent adipocytes, although
      other ancillary hormonal factors may contribute to its blood concentration.
      Relevant gender differences in leptin concentrations have been reported, but it
      is not clear whether the elevated leptin levels in women are an intrinsic
      property of their adipocytes or merely reflect a greater amount of fat reserves.
      To clarify these points, a systematic study with organ culture from human omental
      adipose tissue either stimulated or not with steroid hormones was undertaken in
      samples obtained at surgery from 67 nonobese donors (33 women and 34 men). The
      assay was standardized in periods of 24 h ending at 96 h, with no apparent tissue
      damage. Each adipose tissue sample from a single donor was incubated in
      triplicate, and leptin results are expressed as the mean +/- SEM of the
      integrated secretion to the medium (area under the curve; nanograms of leptin per
      g tissue/48 h). Control nonstimulated samples showed a steady leptin secretion
      along the 96 h studied, with the peak of secretory activity reached at 48 h;
      afterward, the in vitro secretion reached a plateau state. Spontaneous leptin
      secretion in samples from 33 women (3904 +/- 347) was significantly higher (P <
      0.05) than that in samples from 34 men (2940 +/- 323). Coincubation of adipose
      tissue with 1 mumol/L dexamethasone induced a clear-cut leptin increase (P <
      0.05) in samples from women (5848 +/- 624; n = 12), but did not change the
      spontaneous release of leptin in samples from men (3353 +/- 741; n = 6).
      Similarly, coincubation of adipose tissue with 1 mumol/L estradiol induced a
      notable leptin increase (P < 0.05) in samples from women (5698 +/- 688; n = 9),
      whereas it did not alter the secretion in the male samples (3373 +/- 444; n = 6).
      In samples from both sexes, coincubation with 1 mumol/L estrone or progesterone
      had no effect, whereas 1 mumol/L forskolin significantly (P < 0.05) reduced
      leptin release. In conclusion, leptin secretion from omental adipose tissue in
      vitro 1) is significantly higher in samples from women than in samples from men,
      2) is stimulated by dexamethasone and estradiol in women but not in men, 3) is
      not modified by progesterone or estrone in both sexes, and 4) is inhibited by
      forskolin in both genders. This different response to the stimulation of adipose
      tissue may be the biological basis for the gender differences observed in
      circulating levels of human leptin.

PMID- 9626155
TI  - Unique 24-hydroxylated metabolites represent a significant pathway of metabolism
      of vitamin D2 in humans: 24-hydroxyvitamin D2 and 1,24-dihydroxyvitamin D2
      detectable in human serum.
AB  - We have produced evidence for a new metabolic pathway for vitamin D2 in humans
      involving the production of 24-hydroxyvitamin D2 (24OHD2) and 1,24
      dihydroxyvitamin D2 [1,24-(OH)2D2]. These metabolites were produced after either
      a single large dose (10(6) IU) of vitamin D2 or repeated daily doses between
      10(3) and 5 x 10(4) IU. We developed assay systems for the metabolites in human
      serum and showed that in some chronically treated patients, the concentration of
      1,24-(OH)2D2 equalled that of 1,25-(OH)2D2 at about 100 pmol/L. The metabolites
      were identified by high performance liquid chromatography with diode array
      spectrophotometry for 24OHD2 and by high resolution gas chromatography-mass
      spectrometry for 1,24-(OH)2D2. We show that 1,24-(OH)2D2 synthesis can be
      stimulated by PTH, indicating a renal origin for this metabolite and postulate
      that it is formed from 24OHD2, which may be synthesized in liver. We conclude
      from this study that vitamin D2 gives rise to two biologically active products,
      1,24-(OH)2D2 and 1,25-(OH)2D2, and that 1,24-(OH)2D2 could be an attractive
      naturally occurring analog of 1,25-(OH)2D3 for clinical use.

PMID- 9626156
TI  - Delayed low density lipoprotein (LDL) catabolism despite a functional intact LDL
      apolipoprotein B particle and LDL-receptor in a subject with clinical homozygous
      familial hypercholesterolemia.
AB  - We identified a 38-yr-old male patient with the clinical expression of homozygous
      familial hypercholesterolemia presenting as severe coronary artery disease,
      tendon and skin xanthomas, arcus lipoides, and joint pain. The genetic trait
      seems to be autosomal recessive. Interestingly, serum concentrations of
      cholesterol responded well to diet and statins. We had no evidence of an abnormal
      low density lipoprotein (LDL)-apolipoprotein B (apoB) particle, which was
      isolated from the patient using the U937 proliferation assay as a functional test
      of the LDL-binding capacity. The apoB 3500 and apoB 3531 defects were ruled out
      by PCR. In addition, we found no evidence for a defect within the LDL-receptor by
      skin fibroblast analysis, linkage analysis, single-strand conformational
      polymorphism and Southern blot screening across the entire LDL-receptor gene. The
      in vivo kinetics of radioiodinated LDL-apoB were evaluated in the proband and
      three normal controls, subsequently. The LDL-apoB isolated from the patient
      showed a normal catabolism, confirming an intact LDL particle. In contrast the
      fractional catabolic rate (d-1) of autologous LDL in the subject and the normal
      controls revealed a remarkable delayed catabolism of the patient's LDL (0.15 vs.
      0.33-0.43 d-1). In addition, the elevation of LDL-cholesterol in the patient
      resulted from an increased production rate with 22.8 mg/kg per day vs. 12.7-15.7
      mg/kg per day. These data indicate that there is another catabolic defect beyond
      the apoB and LDL-receptor gene causing familial hypercholesterolemia.

PMID- 9626157
TI  - Plasma metanephrines are markers of pheochromocytoma produced by catechol-O
      methyltransferase within tumors.
AB  - This study examined whether the high sensitivity of plasma free metanephrines for
      diagnosis of pheochromocytoma may result from production of free metanephrines
      within tumors. Presence in pheochromocytomas of catechol-O-methyltransferase
      (COMT), the enzyme responsible for conversion of catecholamines to metanephrines,
      was confirmed by Western blot analysis, enzyme assay, and immunohistochemistry.
      Western blot analysis and enzyme assay indicated that membrane-bound and not
      soluble COMT was the predominant form of the enzyme in pheochromocytoma.
      Immunohistochemistry revealed colocalization of COMT in the same chromaffin cells
      where catecholamines are translocated into storage vesicles by the vesicular
      monoamine transporter. Levels of free metanephrines in pheochromocytoma over
      10,000 times higher than plasma concentrations in the same patients before
      removal of tumors indicated production of metanephrines within tumors.
      Comparisons of the production of metanephrines in patients with pheochromocytoma
      with production from catecholamines released or infused into the circulation
      indicated that more than 93% of the consistently elevated levels of circulating
      free metanephrines in patients with pheochromocytoma are derived from metabolism
      before and not after release of catecholamines into the circulation. The data
      indicate that the elevated plasma levels of free metanephrines in patients with
      pheochromocytoma are derived from catecholamines produced and metabolized within
      tumors. Some tumors do not secrete catecholamines, but all appear to metabolize
      catecholamines to free metanephrines, thus explaining the better sensitivity of
      plasma free metanephrines over other tests for diagnosis of pheochromocytoma.

PMID- 9626159
TI  - Up-regulation by progesterone of proliferating cell nuclear antigen and epidermal
      growth factor expression in human uterine leiomyoma.
AB  - Uterine leiomyoma is the most common smooth muscle cell tumor of the myometrium.
      Estrogen and progesterone (P4) are believed to be physiological regulators of
      leiomyoma growth. We recently showed that Bcl-2 protein, an apoptosis-inhibiting
      gene product, was abundantly expressed in leiomyoma relative to its expression in
      the normal myometrium and that Bcl-2 protein expression in cultured leiomyoma
      cells was up-regulated by P4, but down-regulated by 17 beta-estradiol (E2). To
      further characterize the molecular mechanism of sex steroidal regulation of
      leiomyoma growth, we examined the effect of menstrual phase on proliferating cell
      nuclear antigen (PCNA) expression in leiomyoma and investigated whether sex
      steroids could influence PCNA expression in leiomyoma cells cultured under serum
      free conditions by immunoblot and immunohistochemical analyses. As epidermal
      growth factor (EGF) has been shown to mediate estrogen action and to play a
      crucial role in regulating leiomyoma growth, we also investigated the effects of
      sex steroids on the expression of EGF and EGF receptor (EGF-R) in cultured
      leiomyoma cells. The PCNA labeling index in leiomyomas was much greater in the
      secretory, P4-dominated, phase than in the proliferative phase of the menstrual
      cycle and was significantly higher than that in the adjacent normal myometrium
      throughout the menstrual cycle. In monolayer cultures of leiomyoma cells, the
      addition of either E2 (10 ng/mL) or P4 (100 ng/mL) resulted in an increase in
      PCNA expression in the cells compared to that in control cultures, whereas in
      monolayer cultures of myometrial cells, the addition of E2 augmented PCNA
      expression in the cells, but P4 did not. Immunoblot analysis of proteins
      extracted from cultured leiomyoma cells revealed that leiomyoma cells contained
      immunoreactive EGF with a molecular mass of 133 kDa and that the addition of P4
      resulted in a remarkable increase in the expression of 133- and 71-kDa
      immunoreactive EGF in the cells compared to that in control cultures, whereas the
      addition of E2 resulted in a somewhat lower expression of immunoreactive EGF in
      the cells. Furthermore, immunocytochemical analysis with a monoclonal antibody to
      human EGF-R demonstrated that the treatment with E2 augmented EGF-R expression in
      the cells compared to that in untreated cells, but P4 did not. The concentrations
      of sex steroids used were within the physiological tissue concentrations found in
      leiomyomas and myometria. These results indicate that P4 up-regulates the
      expression of PCNA and immunoreactive EGF in leiomyoma cells, whereas E2 up
      regulates the expression of PCNA and EGF-R in those cells. As it is evident that
      EGF plays a crucial role as a local factor in regulating leiomyoma growth, the P4
      induced increase in PCNA expression in leiomyoma cells may be mediated by P4
      induced enhanced expression of EGF-like proteins in the cells, whereas the E2
      induced increase in PCNA expression in leiomyoma cells may be mediated by E2
      induced enhanced expression of EGF-R in those cells. It is, therefore,
      conceivable that P4 and E2 act in combination to stimulate the proliferative
      potential of leiomyoma cells through the induction of EGF-like proteins and EGF-R
      expression in uterine leiomyoma.

PMID- 9626158
TI  - Expression and cellular localization of keratinocyte growth factor and its
      receptor in human hyperplastic prostate tissue.
AB  - It is well recognized that the actions of androgens alone do not explain the
      hyperplastic development of the gland that occurs in elderly men. The increasing
      number of reports confirming the lack of mitogenic activity of androgens coupled
      with the powerful mitogenic activity of growth factors and the discovery of
      growth factor receptors led to an increased interest in the putative role of
      growth factors in prostate physiopathology. We have previously demonstrated the
      presence and the cellular localization of epidermal growth factor and of the
      related peptide, transforming growth factor-alpha, together with their common
      receptor in the epithelial compartment of the human hyperplastic prostate tissue
      (BPH). In the present study we examined the expression and cellular localization
      of messenger ribonucleic acid (RNA) encoding keratinocyte growth factor (KGF) and
      its receptor in human hyperplastic prostate tissue. RT-PCR of total RNA extracted
      from BPH tissues documented the presence of transcripts for KGF and its receptor.
      In situ hybridization with specific RNA probes synthesized from the respective
      complementary DNA demonstrated that KGF mRNA was mainly localized in the stromal
      cells, whereas its receptor was mainly localized in the prostate epithelium.
      Moreover, the mitogenic activity of KGF on cultured BPH cells compared to that of
      other growth factors has been tested. Our findings clearly indicate that KGF has
      the ability to function as a potent mitogen in BPH cells. Our data support the
      hypothesis that KGF plays an important role in prostate growth and that in human
      prostate it seems to act in a paracrine fashion.

PMID- 9626160
TI  - Fas/Fas ligand up-regulation and Bcl-2 down-regulation may be significant in the
      pathogenesis of Hashimoto's thyroiditis.
AB  - Hashimoto's thyroiditis (HT) is an autoimmune disorder characterized by diffuse
      thyroid lymphocytic infiltration and follicle destruction. Cross-linking of the
      Fas receptor with its own ligand (FasL) triggers apoptosis in various systems,
      whereas the Bcl-2 protooncogene inhibits apoptotic cell death. The involvement of
      Fas, FasL, and Bcl-2 in the apoptotic process in HT was evaluated in 15 thyroid
      tissue samples from patients with HT stained for apoptosis and for Fas, FasL, and
      Bcl-2 protein expression. Eight samples from healthy thyroid tissue were used for
      comparison. Thyroid follicles in HT samples exhibited strong staining for Fas and
      FasL and a high percentage of apoptosis (30.3 +/- 14.5%, mean +/- SD), in
      contrast to normal control follicles that exhibited moderate Fas, minimal or no
      FasL, and hardly any apoptosis. Immunostaining for Bcl-2 was high in normal, and
      weak in involved, thyroid follicles. Infiltrating lymphocytes stained weakly for
      FasL and strongly for Bcl-2. We conclude that follicular cells in HT undergo
      apoptosis by concomitant up-regulation of FasL and Fas and down-regulation of Bcl
      2 protein. The lymphocytes do not seem to be directly engaged in the process with
      their own FasL, but they may provide the appropriate cytokine milieu that, in
      turn, up-regulates Fas and/or FasL leading to apoptosis.

PMID- 9626161
TI  - Increased CD69 and human leukocyte antigen-DR expression on T lymphocytes in
      insulin-dependent diabetes mellitus of long standing.
AB  - To better define prevailing activation of circulating T cell subsets in insulin
      dependent diabetes mellitus (IDDM) of recent onset (DM; n = 31; median age +/-
      SD, 28 +/- 6.9 yr) and of long standing (DML; n = 27; age, 33 +/- 10.4 yr; median
      duration of disease, 105 months), CD4+ and CD8+ T cells were analyzed to
      determine their naive and memory subsets as well as their expression of human
      leukocyte antigen (HLA)-DR, interleukin-2 receptor alpha-chain (CD25), and CD69
      by three-color flow cytometry. Twenty-six healthy subjects (HS; age, 32.0 +/- 8.2
      yr) served as controls. No deviation was seen in either IDDM group compared to HS
      in CD25 expression on CD4+ or CD8+ cells or in their CD45RA+ or CD45RA- subsets.
      HLA-DR expression, however, was increased (P < 0.05) in total CD8+ cells and
      CD45RA+ cells, with CD45RA- CD8+ cells joining the prevailing pattern only in
      DML. Among CD4+ cells, increased expression of HLA-DR molecules was restricted to
      total and CD45RA- cells in DML. CD69 expression did not differ between IDDM and
      HS, but differed between DML (CD4+, CD8+, and CD45RA- CD4+) and DM only. In
      conclusion, our data demonstrate that HLA-DR expression in IDDM is restricted to
      memory cells (CD45RA-) among CD4+ cells in DML and is more markedly confined to
      naive (CD45RA+) than to memory CD8+ cells, whereas the early activation antigen
      CD69 is more readily expressed in DML than in DM. The observed activation of
      circulating T cells suggests an ongoing immune process in IDDM both at clinical
      manifestation and after long duration.

PMID- 9626162
TI  - A family with Liddle's syndrome caused by a new missense mutation in the beta
      subunit of the epithelial sodium channel.
AB  - Liddle's syndrome is an autosomal dominant form of salt sensitive hypertension
      caused by mutations in the beta or gamma subunit of the epithelial sodium
      channel. Systematic mutagenesis studies revealed that a conserved PPPXY sequence
      (PY motif) of the C-terminus of the alpha, beta, or gamma subunits might be
      involved in the regulation of the channel activity. However, only two missense
      mutations in the PY motif of the beta subunit have been reported to cause
      Liddle's syndrome. We sequenced the C-termini of the beta and gamma subunits of
      the epithelial sodium channel in a Japanese family clinically diagnosed as having
      Liddle's syndrome and found a new missense mutation in the PY motif of the beta
      subunit, P615S. Expression studies with P615S mutant in Xenopus oocytes resulted
      in an about 3-fold increase in the amiloride-sensitive sodium current compared to
      the wild type (p = 0.001). These findings provide further clinical evidence for
      the hypothesis that a conserved PY motif may be critically important for the
      regulation of the epithelial sodium channel.

PMID- 9626163
TI  - Why do the clinical sequelae of estrogen deficiency affect women more than men?

PMID- 9626164
TI  - Is insulin the only treatment for obese NIDDM patients poorly controlled by oral
      hypoglycemic agents?

PMID- 9626165
TI  - Further evidence for a dominant form of familial persistent hyperinsulinemic
      hypoglycemia of infancy: a family with documented hyperinsulinemia in two
      generations.

PMID- 9626166
TI  - Comment on human fetal pituitary expresses functional GHRP receptors.

PMID- 9626167
TI  - American Heart Association call to action: obesity as a major risk factor for
      coronary heart disease. AHA Nutrition Committee.

PMID- 9626168
TI  - Pathophysiology of sudden coronary death in women. Implications for prevention.

PMID- 9626169
TI  - Public locations of cardiac arrest. Implications for public access
      defibrillation.
AB  - BACKGROUND: The purpose of this study was to describe the public locations of
      cardiac arrest and to estimate the annual incidence of cardiac arrest per site to
      determine optimal placement of automatic external defibrillators (AEDs). This was
      a retrospective cohort study. METHODS AND RESULTS: Locations of cardiac arrest
      were abstracted from data collected by emergency medical service programs in
      Seattle and King County, Washington, from January 1, 1990, through December 31,
      1994. Types of commercial and civic establishments were tallied and grouped into
      23 location categories consistent with Standard Industrial Codes, and the number
      of sites within each location category was determined. With the addition of
      "public outdoors" and "automobiles" as categories, there were 25 location
      categories. During the study period, 7185 arrests occurred, 1130 (16%) of which
      were in public locations. An annual incidence of cardiac arrest per site was
      calculated. Ten location categories with 172 sites were identified as having a
      higher incidence of cardiac arrest (> or = .03 per year per site). Thirteen
      location categories had a lower incidence of arrest (< or = .01 per year per
      site). There were approximately 71,000 sites within these categories.
      CONCLUSIONS: Placement of 276 AEDs in the 172 higher-incidence sites would have
      provided treatment for 134 cardiac arrest patients in a 5-year period, 60% of
      whom were in ventricular fibrillation. We estimate between 8 and 32 lives could
      be saved in 5 years. To cover the remaining 347 arrests occurring in public in a
      5-year period, defibrillators would have to be placed in 71,000 sites, not
      including outdoors and automobiles. Placement of AEDs in public locations can be
      guided by the site-specific incidence of arrest.

PMID- 9626170
TI  - Effect of risk factors on the mechanism of acute thrombosis and sudden coronary
      death in women.
AB  - BACKGROUND: Traditional risk factors have been linked to atherosclerotic heart
      disease in women. However, the effect of risk factors and menopausal status on
      the mechanism of sudden coronary death is unknown. METHODS AND RESULTS: We
      examined 51 cases of sudden coronary death and 15 hearts from women who died of
      trauma. Coronary deaths were divided into four mechanisms of death: ruptured
      plaque with acute thrombus (n = 8), eroded plaque with acute thrombus (n = 18),
      stable plaque with healed infarct (n = 18), and stable plaque without infarction
      (n = 7). Vulnerable plaques prone to rupture were defined as those with a thin,
      fibrous cap infiltrated by macrophages and were quantitated in coronary deaths
      and control subjects. Total cholesterol (TC), HDL cholesterol, glycosylated
      hemoglobin, cigarette smoking, and hypertension were determined in each case.
      Compared with control subjects, women with plaque ruptures had elevated TC (270
      +/- 55 versus 194 +/- 44 mg/dL, P = 0.002), and those with erosions were more
      likely to be smokers (78% versus 33%, P = 0.01). Women with stable plaque and
      healed infarct had elevated glycosylated hemoglobin (10.2 +/- 5.0% versus 6.4 +/-
      0.4% in control subjects, P = 0.001) and were more likely to be hypertensive (50%
      versus 15% in control subjects, P = 0.03). By multivariate analysis, cigarette
      smoking was associated with plaque erosion (P = 0.03, odds ratio [OR] 21),
      glycoslyated hemoglobin with stable plaque and healed infarct (P = 0.03, OR 41),
      TC with plaque rupture (P = 0.02, OR 7), and hypertension with stable plaque with
      healed infarct (P = 0.02, OR 15). Seven of 8 plaque ruptures occurred in women >
      50 years of age versus 3 of 18 erosions (P = 0.001). In cases of coronary death,
      vulnerable plaques were associated with elevated cholesterol (P = 0.002) and age
      > 50 years (P = 0.002), independent of other risk factors. CONCLUSIONS: In women,
      traditional risk factors have distinct effects on the mechanisms of sudden
      coronary death, which vary by menopausal status. Effective risk factor
      modification may therefore differ between younger and older women and may be
      targeting different mechanisms of plaque instability.

PMID- 9626171
TI  - Independent prognostic significance of ischemic ST-segment response limited to
      recovery from treadmill exercise in asymptomatic subjects.
AB  - BACKGROUND: Although exercise-induced ST depression is an independent predictor
      of future coronary events in asymptomatic populations, the predictive value of ST
      depression beginning after exercise cessation is unknown. METHODS AND RESULTS: We
      analyzed the treadmill exercise tests of 825 healthy volunteers who were 22 to 89
      years of age from the Baltimore Longitudinal Study of Aging. All subjects were
      free from coronary heart disease by history, physical examination, and resting
      ECG. From 825 participants, 611 (group 0) had no ischemic ST-segment changes
      during or after treadmill exercise, while 214 subjects developed > or = 1-mm flat
      or downsloping ST depression: 151 (group 1) had ST changes starting during
      exercise, and 63 (group 2) had changes limited to recovery. Groups 1 and 2 were
      similar in age, sex, smoking status, hypertension prevalence, fasting plasma
      glucose, and serum cholesterol (CHOL). However, both groups were older and had
      higher CHOL and prevalence of hypertension than group 0. Treadmill exercise
      duration, peak oxygen consumption, and maximal heart rate were similar between
      groups 1 and 2 but were lower than in group 0 (each P < 0.05). During a mean
      follow-up time of 9 years, 55 subjects developed coronary events (angina
      pectoris, myocardial infarction, or coronary death): 21 of 611 (3.4%) in group 0,
      22 of 151 (14.6%) in group 1, and 12 of 63 (19%) in group 2 (P = 0.001). By
      survival analysis, the risk of coronary events was similar in groups 1 and 2 but
      significantly higher than in group 0 (P < 0.0001). Multiple logistic regression
      showed that age (odds ratio [OR] = 1.07 per year, P = 0.00001), CHOL (OR = 1.02
      per 1 mg, P = 0.0001), and presence of ST-segment depression (OR = 2.59, P =
      0.007 and OR = 2.38, P = 0.04 for groups 1 and 2, respectively) were independent
      predictors of events. CONCLUSIONS: Thus, ischemic ST-segment changes developing
      during recovery from treadmill exercise in apparently healthy individuals have
      adverse prognostic significance similar to those appearing during exercise.

PMID- 9626172
TI  - Long-term L-arginine supplementation improves small-vessel coronary endothelial
      function in humans.
AB  - BACKGROUND: Coronary endothelial dysfunction is characterized by an imbalance
      between endothelium-derived vasodilating and vasoconstricting factors and
      coronary vasoconstriction in response to the endothelium-dependent vasodilator
      acetylcholine. Thus, the present double-blind, randomized study was designed to
      test the hypothesis that long-term, 6-month supplementation of L-arginine, the
      precursor of the endothelium-derived vasodilator NO, reverses coronary
      endothelial dysfunction to acetylcholine in humans with nonobstructive coronary
      artery disease. METHODS AND RESULTS: Twenty-six patients without significant
      coronary artery disease on coronary angiography and intravascular ultrasound were
      blindly randomized to either oral L-arginine or placebo, 3 g TID. Endothelium
      dependent coronary blood flow reserve to acetylcholine (10(-6) to 10(-4) mol/L)
      was assessed at baseline and after 6 months of therapy. There was no difference
      between the two study groups in clinical characteristics or in the coronary blood
      flow in the response to acetylcholine at baseline. After 6 months, the coronary
      blood flow in response to acetylcholine in the subjects who were taking L
      arginine increased compared with the placebo group (149 +/- 20% versus 6 +/- 9%,
      P < 0.05). This was associated with a decrease in plasma endothelin
      concentrations and an improvement in patients' symptoms scores in the L-arginine
      treatment group compared with the placebo group. CONCLUSIONS: Long-term oral L
      arginine supplementation for 6 months in humans improves coronary small-vessel
      endothelial function in association with a significant improvement in symptoms
      and a decrease in plasma endothelin concentrations. This study proposes a role
      for L-arginine as a therapeutic option for patients with coronary endothelial
      dysfunction and nonobstructive coronary artery disease.

PMID- 9626173
TI  - The cost-effectiveness of automatic implantable cardiac defibrillators: results
      from MADIT. Multicenter Automatic Defibrillator Implantation Trial.
AB  - BACKGROUND: The recently reported Multicenter Automatic Defibrillator
      Implantation Trial (MADIT) showed improved survival in selected asymptomatic
      patients with coronary disease and nonsustained ventricular tachycardia. The
      economic consequences of defibrillator management in this patient population are
      unknown. METHODS AND RESULTS: Patients were followed up to quantify their use of
      healthcare services, including hospitalizations, physician visits, medications,
      laboratory tests, and procedures, during the trial. The costs of these services,
      including the costs of the defibrillator, were determined in patients randomized
      to defibrillator and nondefibrillator therapy. Incremental cost-effectiveness
      ratios were calculated by relating these costs to the increased survival
      associated with the use of the defibrillator. The average survival for the
      defibrillator group over a 4-year period was 3.66 years compared with 2.80 years
      for conventionally treated patients. Accumulated net costs were $97,560 for the
      defibrillator group compared with $75,980 for individuals treated with
      medications alone. The resulting incremental cost-effectiveness ratio of $27,000
      per life-year saved compares favorably with other cardiac interventions.
      Sensitivity analyses showed that the incremental cost-effectiveness ratio would
      be reduced to approximately $23,000 per life-year saved if transvenous
      defibrillators were used instead of the older devices, which required thoracic
      surgery for implantation. CONCLUSIONS: An implanted cardiac defibrillator is cost
      effective in selected individuals at high risk for ventricular arrhythmias.

PMID- 9626174
TI  - Atrial mapping and radiofrequency catheter ablation in patients with idiopathic
      atrial fibrillation. Electrophysiological findings and ablation results.
AB  - BACKGROUND: Knowledge of the electrophysiological substrates and the cure of
      atrial fibrillation (AF) is still unsatisfactory. The goal of this study was to
      evaluate the electrophysiological features of idiopathic AF and their
      relationship to the results of radiofrequency (RF) catheter ablation of AF and
      the safety and effectiveness of this procedure. METHODS AND RESULTS: Sixteen
      patients with idiopathic AF underwent atrial mapping during AF and then RF
      ablation in the right atrium. The atrial activation was simultaneously recorded
      in four regions in the right atrium: high lateral wall (HL), low lateral wall
      (LL), high septum (HS), and low septum (LS) and in the left atrium through the
      coronary sinus (CS). In these regions, we evaluated the atrial fibrillation
      intervals (FF) and the morphological features of AF recordings by Wells'
      classification. No complications occurred during RF ablation. Of the 16 patients,
      9 (56%) without AF recurrences during the follow-up (11 +/- 4 months) were
      considered successfully ablated. These patients showed a significantly shorter
      mean FF interval in the HS and the LS (122 +/- 32 and 126 +/- 28 ms,
      respectively), than in the HL and LL (159 +/- 24 and 156 +/- 28 ms,
      respectively). Moreover, the septum had more irregular electrical activity with
      greater beat-to-beat changes in FF and a higher prevalence of type III AF than
      the lateral region. The CS had similar behavior to the septum. Conversely,
      patients with unsuccessful ablation had an irregular atrial activity in the
      lateral wall, septum, and CS with no significant differences between the
      different sites. CONCLUSIONS: Right atrial endocardial catheter ablation of AF is
      a safe procedure and may be effective in some patients with idiopathic AF. The
      atrial mapping during AF showed a more disorganized right atrial activation in
      the septum than in the lateral wall in patients with successful ablation.

PMID- 9626175
TI  - Preserved relative dispersion but blunted stimulation of mean flow, absolute
      dispersion, and blood volume by insulin in skeletal muscle of patients with
      essential hypertension.
AB  - BACKGROUND: We examined the integrity of the effects of insulin on mean muscle
      blood flow, flow heterogeneity, and blood volume in essential hypertension.
      METHODS AND RESULTS: Positron emission tomography, combined with [15O]H2O and
      [15O]CO as tracers for direct measurement of blood flow and volume in skeletal
      muscle, and a new bayesian iterative reconstruction algorithm allowing pixel-by
      pixel quantitation of blood flow and flow dispersion, were used. Measurements
      were performed basally after an overnight fast and under normoglycemic
      hyperinsulinemic conditions in 11 newly diagnosed, untreated mildly hypertensive
      men (age, 35 +/- 1 years; body mass index, 25.2 +/- 0.4 kg/m2, blood pressure 141
      +/- 4/96 +/- 2 mm Hg, mean +/- SE) and 11 matched normotensive men. Insulin
      stimulated whole body glucose uptake was significantly decreased in the
      hypertensive men (41 +/- 4 mumol/kg per minute) compared with the normotensive
      (59 +/- 4 mumol/kg per minute, P < 0.005) men. Mean blood flow in skeletal muscle
      was significantly lower in the hypertensive than the normal subjects basally (1.7
      +/- 0.2 versus 2.7 +/- 0.4 mL/0.1 kg per minute, P < 0.05) and during
      hyperinsulinemia (2.3 +/- 0.2 versus 4.2 +/- 0.8, P < 0.05). The flow response to
      insulin (0.6 +/- 0.2 versus 1.9 +/- 0.5 mL/0.1 kg per minute, hypertensive versus
      normal subjects, P < 0.05) was also significantly blunted. Muscle blood volume
      was significantly lower in the hypertensive than in the normal subjects, both
      basally (3.0 +/- 0.2 versus 3.5 +/- 0.2 mL/0.1 kg, P < 0.05) and during
      hyperinsulinemia (3.1 +/- 0.2 versus 4.0 +/- 0.2 mL/0.1 kg muscle, P < 0.02). The
      increase in muscle blood volume by insulin was significant in the normal (P <
      0.05) but not the hypertensive subjects. Regional pixel-by-pixel analysis within
      femoral muscles revealed significant spatial heterogeneity of blood flow. Insulin
      increased absolute dispersion of blood flow significantly more in the normal
      subjects than in the hypertensive subjects (P < 0.05). CONCLUSIONS: True flow
      heterogeneity, as judged from the coefficients of variation (relative
      dispersion), was comparable between the groups basally and during
      hyperinsulinemia. We conclude that mean flow, its absolute dispersion, and blood
      volume exhibit insulin resistance in patients with essential hypertension.

PMID- 9626176
TI  - Sleep apnea in 81 ambulatory male patients with stable heart failure. Types and
      their prevalences, consequences, and presentations.
AB  - BACKGROUND: Heart failure is a highly prevalent disorder that continues to be
      associated with repeated hospitalizations, high morbidity, and high mortality.
      Sleep-related breathing disorders with repetitive episodes of asphyxia may
      adversely affect heart function. The main aims of this study were to determine
      the prevalence, consequences, and differences in various sleep-related breathing
      disorders in ambulatory male patients with stable heart failure. METHODS AND
      RESULTS: This article reports the results of a prospective study of 81 of 92
      eligible patients with heart failure and a left ventricular ejection fraction <
      45%. There were 40 patients without (hourly rate of apnea/hypopnea, 4 +/- 4;
      group 1) and 41 patients with (51% of all patients; hourly rate of
      apnea/hypopnea, 44 +/- 19; group 2) sleep apnea. Sleep disruption and arterial
      oxyhemoglobin desaturation were significantly more severe and the prevalence of
      atrial fibrillation (22% versus 5%) and ventricular arrhythmias were greater in
      group 2 than in group 1. Forty percent of all patients had central sleep apnea,
      and 11% had obstructive sleep apnea. The latter patients had significantly
      greater mean body weight (112 +/- 30 versus 75 +/- 16 kg) and prevalence of
      habitual snoring (78% versus 28%). However, the hourly rate of episodes of apnea
      and hypopnea (36 +/- 10 versus 47 +/- 21), episodes of arousal (20 +/- 14 versus
      23 +/- 11), and desaturation (lowest saturation, 72 +/- 11% versus 78 +/- 12%)
      were similar in patients with these different types of apnea. CONCLUSIONS: Fifty
      one percent of male patients with stable heart failure suffer from sleep-related
      breathing disorders: 40% from central and 11% from obstructive sleep apnea. Both
      obstructive and central types of sleep apnea result in sleep disruption and
      arterial oxyhemoglobin desaturation. Patients with sleep apnea have a high
      prevalence of atrial fibrillation and ventricular arrhythmias.

PMID- 9626177
TI  - Diabetes and dyslipidemia. A new model for transplant coronary artery disease.
AB  - BACKGROUND: Clinical observations suggest that transplant coronary artery disease
      (TxCAD) is immunologically mediated but may be accelerated by metabolic
      derangements. We developed a rat model of heterotopic heart transplantation in
      the presence of diabetes and dyslipidemia to further study their role in TxCAD
      development. METHODS AND RESULTS: Major histocompatibility complex-mismatched
      strains of inbred rats underwent heterotopic heart transplantation (ACI-to-Lewis
      allografts). Diabetes (DM) was induced by streptozotocin injection (80 mg/kg)
      after transplantation; dyslipidemia was worsened by feeding of a 60% high
      fructose diet (+F). Allograft transplants were divided into four groups: (1)
      +DM/+F; (2) +DM/-F; (3) -DM/+F; and (4) -DM/-F. Isograft transplants (Lewis to
      Lewis, +DM/+/-F) were controls. All animals received daily cyclosporine (5
      mg/kg). Grafts surviving > 30 days were evaluated for TxCAD on histological
      sections and graded 0 to 5 for intimal thickness. All streptozotocin-treated
      animals were diabetic within 2 weeks, with fourfold increases in plasma glucose
      concentrations versus nondiabetics. Severe TxCAD was observed in diabetic
      allografts only. The mean grade of TxCAD in diabetic allografts was 3.2 +/- 0.5
      versus 1.1 +/- 0.4 in diabetic isografts (P < 0.03) and zero TxCAD in nondiabetic
      allografts (P < or = 0.0001). Fructose feeding resulted in a 1.5-fold higher
      triglyceride and a 1.3-fold higher cholesterol level versus the regular diet (-F)
      but showed no independent contribution to the development of TxCAD. CONCLUSIONS:
      These findings suggest that metabolic derangements associated with diabetes play
      an important role in TxCAD development in heterotopic ACI-to-Lewis rat heart
      transplantation. In this model of TxCAD in major histocompatibility complex
      mismatched, diabetic, and dyslipidemic rats, immunologic and metabolic mechanisms
      that contribute to TxCAD can be further delineated and approaches to its
      prevention assessed.

PMID- 9626178
TI  - EndothelinA receptor blockade improves nitric oxide-mediated vasodilation in
      monocrotaline-induced pulmonary hypertension.
AB  - BACKGROUND: Nitric oxide (NO) and endothelin (ET) have been implicated in the
      pathogenesis of pulmonary hypertension (PH). Chronic ETA antagonist therapy
      reduces PH in monocrotaline (MCT)-treated rats. Interactions between the L
      arginine-NO pathway and the ET system have been described. We therefore studied
      the effect of long-term treatment with an oral ETA antagonist (LU 135252) on NO
      related vasodilation in isolated lungs from control rats and rats with MCT
      induced PH. METHODS AND RESULTS: Three weeks after MCT injection, PH was
      associated with an increase in right ventricular pressure (from 27.4 +/- 0.9 to
      66.6 +/- 4.1 mm Hg) and a decrease in endothelium-independent vasodilation in
      response to sodium nitroprusside (10(-10) to 10(-5) mol/L; delta Emax, from 11.1
      +/- 0.9 to 2.7 +/- 0.3 mm Hg). Endothelium-dependent vasodilation in response to
      acetylcholine (10(-9) to 10(-4) mol/L) and the calcium ionophore A23187 (10(-9)
      to 10(-7) mol/L) remained unaffected. Treatment with LU 135252 did not
      significantly affect the endothelium-dependent and -independent vasodilations in
      control rats. However, in MCT-treated rats, LU 135252 therapy significantly
      reduced right ventricular pressure (39.7 +/- 2.1 mm Hg), potentiated
      acetylcholine-induced vasodilatation (delta Emax, from 1.6 +/- 0.2 to 3.7 +/- 0.4
      mm Hg), and improved the responses to sodium nitroprusside (delta Emax, from 2.7
      +/- 0.3 to 5.6 +/- 0.6 mm Hg). LU 135252 did not significantly alter the non
      receptor-mediated endothelium-dependent vasodilation to A23187 or pulmonary
      constitutive NO synthase activity. CONCLUSIONS: MCT PH is associated with a
      reduced smooth muscle responsiveness to NO but a maintained endothelium-dependent
      vasodilatory potency. Long-term ETA antagonist therapy not only restores smooth
      muscle responsiveness to NO but also increases endothelium-dependent dilation in
      response to acetylcholine. This mechanism may contribute to the therapeutic
      benefit of ETA antagonists in PH.

PMID- 9626179
TI  - Induction of plasminogen activator inhibitor type 1 and type 1 collagen
      expression in rat cardiac microvascular endothelial cells by interleukin-1 and
      its dependence on oxygen-centered free radicals.
AB  - BACKGROUND: Ischemia with or without reperfusion induces the release of diverse
      products from monocytes, including cytokines such as interleukin-1 (IL-1). To
      determine whether these phenomena modulate fibrinolysis and potentially
      exacerbate impairment of the macrocirculation, microcirculation, or both, we
      characterized the effects of IL-1 on the expression of fibrinolytic system and
      matrix proteins in rat cardiac microvascular endothelial cells (CMECs). METHODS
      AND RESULTS: Confluent CMECs were exposed to IL-1 in serum-free medium for 24
      hours, and cell-conditioned medium was assayed for plasminogen activator
      inhibitor type 1 (PAI-1), the primary physiological inhibitor of plasminogen
      activators, and for type 1 collagen with Western blotting. IL-1 (2 ng/mL)
      specifically increased the accumulation of PAI-1 (4.4 +/- 0.6-fold; mean +/- SD;
      n = 9) without affecting tissue plasminogen activator (t-PA) or urokinase
      plasminogen activator (u-PA) levels, which remained unchanged. IL-1 increased the
      accumulation of collagen in conditioned media by 3.5 +/- 0.7-fold (n = 6).
      Conversely, the accumulation of both PAI-1 and collagen induced by IL-1 was
      inhibited with an IL-1 receptor antagonist (200 ng/mL; n = 6) and with
      cycloheximide (10 micrograms/mL; n = 6), implying that protein synthesis was a
      requirement for the effect. To determine whether the IL-1 effect was mediated by
      induction of oxygen-centered free radical production, known to be induced by IL
      1, we exposed the cells to the hydroxyl radical scavenger tetramethylthiourea (10
      mmol/L) and observed abolition of the IL-1-induced increase in the expression of
      PAI-1 and collagen (n = 6). Conversely, superoxides (generated with 10 mU/mL
      xanthine oxidase plus 0.6 mmol/L hypoxanthine, and 100 mumol/L hydrogen peroxide)
      induced the accumulation of PAI-1 and collagen (n = 6). IL-1 (1 microgram/kg body
      wt) and lipopolysaccharide (50 micrograms/kg body wt) administered in vivo
      increased PAI-1 protein in rat hearts as detected with Western blotting and PAI-1
      immunostaining of rat heart microvessels, indicating the effects delineated in
      vitro were paralleled by effects in vivo. CONCLUSIONS: These results indicate
      that IL-1-induced oxygen-centered free radicals stimulate elaboration of PAI-1
      and collagen by CMECs. Accordingly, microvascularly mediated inhibition of
      fibrinolysis may predispose to the persistence of microvascular thrombi, thereby
      contributing to impaired microcirculatory function, the no-reflow phenomenon, and
      cardiac dysfunction after ischemia and reperfusion.

PMID- 9626180
TI  - Colchicine treatment for recurrent pericarditis. A decade of experience.
AB  - BACKGROUND: The most troublesome complication of acute pericarditis is recurrent
      episodes of pericardial inflammation, occurring in 15% to 32% of cases. The cause
      of the recurrence is usually unknown, although in some cases it may be traced to
      viral infection or may be a consequence of coronary artery bypass grafting. The
      optimal method for prevention has not been fully established; accepted modalities
      include nonsteroidal anti-inflammatory drugs, corticosteroids, immunosuppressive
      agents, and pericardiectomy. METHODS AND RESULTS: Based on the proven efficacy of
      colchicine therapy for familial Mediterranean fever (recurrent polyserositis),
      several small studies have used colchicine successfully to prevent recurrence of
      acute pericarditis after failure of conventional treatment. Recently, we reported
      the results from the largest multicenter international study on 51 patients who
      were treated with colchicine to prevent further relapses and who were followed up
      for < or = 10 years. CONCLUSIONS: In light of new trial data that have
      accumulated in the past decade, we review the evidence for the efficacy and
      safety of colchicine for the prevention of recurrent episodes of pericarditis.
      Clinical and personal experience shows that colchicine may be an extremely
      promising adjunct to conventional treatment and may ultimately serve as the
      initial mode of treatment, especially in idiopathic cases.

PMID- 9626181
TI  - Images in cardiovascular medicine. Three-dimensional imaging of atrial myxoma.

PMID- 9626182
TI  - Image in cardiovascular medicine. Eustachian valve mimicking intracardiac mass.

PMID- 9626183
TI  - Magnetic resonance imaging of acute stroke.
AB  - In the investigation of ischemic stroke, conventional structural magnetic
      resonance (MR) techniques (e.g., T1-weighted imaging, T2-weighted imaging, and
      proton density-weighted imaging) are valuable for the assessment of infarct
      extent and location beyond the first 12 to 24 hours after onset, and can be
      combined with MR angiography to noninvasively assess the intracranial and
      extracranial vasculature. However, during the critical first 6 to 12 hours, the
      probable period of greatest therapeutic opportunity, these methods do not
      adequately assess the extent and severity of ischemia. Recent developments in
      functional MR imaging are showing great promise for the detection of developing
      focal cerebral ischemic lesions within the first hours. These include (1)
      diffusion-weighted imaging, which provides physiologic information about the self
      diffusion of water, thereby detecting one of the first elements in the
      pathophysiologic cascade leading to ischemic injury; and (2) perfusion imaging.
      The detection of acute intraparenchymal hemorrhagic stroke by susceptibility
      weighted MR has also been reported. In combination with MR angiography, these
      methods may allow the detection of the site, extent, mechanism, and tissue
      viability of acute stroke lesions in one imaging study. Imaging of cerebral
      metabolites with MR spectroscopy along with diffusion-weighted imaging and
      perfusion imaging may also provide new insights into ischemic stroke
      pathophysiology. In light of these advances in structural and functional MR,
      their potential uses in the study of the cerebral ischemic pathophysiology and in
      clinical practice are described, along with their advantages and limitations.

PMID- 9626184
TI  - Quinolinic acid is increased in CSF and associated with mortality after traumatic
      brain injury in humans.
AB  - We tested the hypothesis that quinolinic acid, a tryptophan-derived N-methyl-D
      aspartate agonist produced by macrophages and microglia, would be increased in
      CSF after severe traumatic brain injury (TBI) in humans, and that this increase
      would be associated with outcome. We also sought to determine whether therapeutic
      hypothermia reduced CSF quinolinic acid after injury. Samples of CSF (n = 230)
      were collected from ventricular catheters in 39 patients (16 to 73 years old)
      during the first week after TBI, (Glasgow Coma Scale [GCS] < 8). As part of an
      ongoing study, patients were randomized within 6 hours after injury to either
      hypothermia (32 degrees C) or normothermia (37 degrees C) treatments for 24
      hours. Otherwise, patients received standard neurointensive care. Quinolinic acid
      was measured by mass spectrometry. Univariate and multivariate analyses were used
      to compare CSF quinolinic acid concentrations with age, gender, GCS, time after
      injury, mortality, and treatment (hypothermia versus normothermia). Quinolinic
      acid concentration in CSF increased maximally to 463 +/- 128 nmol/L (mean +/-
      SEM) at 72 to 83 hours after TBI. Normal values for quinolinic acid concentration
      in CSF are less than 50 nmol/L. Quinolinic acid concentration was increased 5- to
      50-fold in many patients. There was a powerful association between time after TBI
      and increased quinolinic acid (P < 0.00001), and quinolinic acid was higher in
      patients who died than in survivors (P = 0.003). Age, gender, GCS, and treatment
      (32 degrees C versus 37 degrees C) did not correlate with CSF quinolinic acid.
      These data reveal a large increase in quinolinic acid concentration in CSF after
      TBI in humans and raise the possibility that this macrophage-derived excitotoxin
      may contribute to secondary damage.

PMID- 9626185
TI  - Involvement of thromboxane A2 in the mediation of the contractile effect induced
      by inhibition of nitric oxide synthesis in isolated rat middle cerebral arteries.
AB  - Inhibition of nitric oxide (NO) synthesis induces vasoconstriction and reduction
      of the blood flow in the brain, indicating that basal release of NO provides a
      resting vasorelaxant tone in the cerebral circulation. In the present study, the
      contractile effect of the NO synthase blocker NG-nitro-L-arginine (100 mumol/L)
      in isolated rat middle cerebral arteries was attenuated markedly in the presence
      of the cyclooxygenase inhibitor indomethacin (5 mumol/L), the thromboxane A2
      synthase inhibitor ridogrel (10 mumol/L), or the thromboxane receptor antagonist
      ICI 192605 (100 mumol/L). These results indicate that removal of the endogenous
      NO stimulates the release of thromboxane A2 in cerebral vessels and basal NO
      production regulates the resting cerebrovascular tone, at least in part, by
      suppressing thromboxane A2.

PMID- 9626186
TI  - Quantification of muscarinic cholinergic receptors with [11C]NMPB and positron
      emission tomography: method development and differentiation of tracer delivery
      from receptor binding.
AB  - Quantification of human brain muscarinic cholinergic receptors was investigated
      with the use of [11C]N-methyl-4-piperidyl benzylate (NMPB) and positron emission
      tomography (PET). Whole-brain uptake of NMPB at 90 to 110 minutes after
      intravenous injection was approximately 10% of the administered dose. The initial
      cerebral distribution of NMPB corresponded to the pattern of cerebral perfusion;
      however, at progressively longer postinjection intervals, regional distinctions
      consistent with muscarinic receptor binding were evident: activity at 90 to 110
      minutes postinjection was highest in the striatum and cerebral cortex,
      intermediate in the thalamus and pons, and lowest in the cerebellum. After the
      development of a chromatographic system for isolation of authentic [11C]NMPB in
      plasma, tracer kinetic modeling was used to estimate receptor binding from the
      cerebral and arterial plasma tracer time-courses. Ligand transport rate and
      receptor-binding estimates were obtained with the use of compartmental models and
      analytical methods of varying complexity, including a two-parameter pixel-by
      pixel-weighted integral approach and regional least-squares curve-fitting
      analyses employing both two- and three-compartment model configurations. In test
      retest experiments, precision of the methods and their abilities to distinguish
      altered ligand delivery from binding in occipital cortex during an audiovisual
      presentation were evaluated. Visual stimulation increased the occipital blood-to
      brain NMPB transport rate by 25% to 46% in estimates arising from the various
      approaches. Weighted integral analyses resulted in lowest apparent transport
      changes and in a concomitant trend toward apparent binding increases during
      visual activation. The regional least-squares procedures were superior to the
      pixel-by-pixel method in isolating the effects of altered tracer delivery from
      receptor-binding estimates, indicating larger transport effects and unaltered
      binding. Precision was best (less than 10% test-retest differences) for the
      weighted integral analyses and was somewhat lower in the least-squares analyses
      (10-25% differences). The authors conclude that pixel-by-pixel-weighted integral
      analyses of NMPB distribution introduce transport biases into receptor-binding
      estimates. Similar confounding effects also are predicted in noncompartmental
      analyses of delayed radiotracer distribution. The use of regional nonlinear least
      squares fitting to two- and three-compartment models, although more labor
      intensive, provides accurate distinction of receptor-binding estimates from
      tracer delivery with acceptable precision in both intra- and intersubject
      comparisons.

PMID- 9626187
TI  - Cerebral glucose transport and metabolism in preterm human infants.
AB  - Few data regarding early developmental changes in cerebral (blood-to-brain)
      glucose transport (CTXglc) and CMRglc are available for humans. We measured CBF,
      CTXglc, and CMRglc with positron emission tomography at 4 to 7 days of life in
      six preterm human infants whose estimated gestational age was 25 to 34 weeks. The
      Michaelis-Menten constants Kt and Tmax were estimated from CTXglc and the
      calculated cerebral capillary plasma glucose concentration. Mean CMRglc was 8.8
      mumol 100 g-1 min-1. The CMRglc did not correlate with plasma glucose
      concentration (r = .315, P = .543), whereas CTXglc showed a significant
      correlation with plasma glucose concentration (r = .836, P = .038). Estimation of
      the Michaelis-Menten constants from the best fit to the measured data produced
      values of Kt = 6.0 mumol mL-1 and Tmax = 32.6 mumol 100 g-1 min-1. These values
      for Kt in the developing human brain are similar to those that have been reported
      for the mature brain of adolescent and adult humans and adult nonhuman primates,
      indicating the affinity of the glucose transport protein for D-glucose is
      similar. However, Tmax is approximately one third to one half of the comparable
      values for mature brain, indicating a reduced number of available luminal
      transporters.

PMID- 9626188
TI  - Cerebral circulation in sleep: vasodilatory response to cerebral hypotension.
AB  - Little is known of the factors that regulate CBF in sleep. We therefore studied
      10 lambs to assess the vasodilatory processes that underlie cerebral
      autoregulation during sleep. Lambs, instrumented to measure CBF (flow probe on
      the superior sagittal sinus), sleep state, and cerebral perfusion pressure (CPP),
      were rapidly made hypotensive by inflating a cuff around the brachiocephalic
      artery to reduce CPP to 30 mm Hg in each state. During control periods, cerebral
      vascular resistance (CVR in mm Hg/mL/min) was lower in active sleep (2.8 +/- 0.3,
      mean +/- SD, P < or = 0.001) than in wakefulness (3.9 +/- 0.6) and quiet sleep
      (4.3 +/- 0.6). The CVR decreased promptly in each state as CPP was lowered. The
      time (seconds) required for maximal cerebral vasodilation to occur was longer in
      active sleep (35 +/- 11) than in quiet sleep (20 +/- 6, P < or = 0.001) and
      wakefulness (27 +/- 11, P < or = 0.05). The CVR decreased less in active sleep
      (0.6 +/- 0.3, P < or = 0.001) than in quiet sleep (1.5 +/- 0.3), although the
      changes in CPP induced with brachiocephalic occlusion were equal in each state.
      In conclusion, our studies provide the first evidence that the vasoactive
      mechanisms that underlie autoregulation of the cerebral circulation function
      during sleep. Moreover, our data reveal that the speed and the magnitude of the
      vasodilatory reserves available for autoregulation are significantly less in
      active sleep than in quiet sleep.

PMID- 9626189
TI  - Transient global ischemia triggers expression of the DNA damage-inducible gene
      GADD45 in the rat brain.
AB  - Using in situ hybridization, Northern blot analysis, Western blot analysis, and
      immunocytochemistry, mRNA and protein expression of the novel DNA damage
      inducible gene GADD45 was examined in the rat brain at 0.5, 2, 4, 8, 16, 24, 48,
      and 72 hours after 15 minutes of transient global ischemia. Transient ischemia
      produced by the four-vessel occlusion method resulted in DNA double-strand breaks
      and delayed neuronal cell death in vulnerable neurons of the hippocampal CA1
      sector, the hilus, dorsal caudate-putamen, and thalamus, as shown by in situ DNA
      nick end-labeling and histologic staining. GADD45 mRNA was transiently increased
      in less-vulnerable regions such as the parietal cortex (up to 8 hours after
      ischemia) and dentate granule cells (up to 24 hours after ischemia) but was
      persistently increased in vulnerable neurons such as CA1 pyramidal neurons (up to
      48 hours). GADD45 immunoreactivity was increased in both vulnerable and less
      vulnerable regions at earlier reperfusion periods (4 to 16 hours), but thereafter
      immunoreactivity was decreased below control levels in most vulnerable regions
      before delayed cell death and DNA double-strand breaks. At 72 hours after
      transient ischemia, a moderate increase in GADD45 immunoreactivity was still
      detectable in some CA3 neurons and in a few surviving neurons in the CA1 region.
      Double staining performed at 16 to 72 hours after ischemia revealed that GADD45
      immunoreactivity was persistently increased in neurons that did not develop DNA
      damage. Because GADD45 protein may participate in the DNA excision repair process
      and because it has been shown that this protein is also overexpressed in neurons
      that survive focal ischemia and kainate-induced epileptic seizures, the results
      reported here support the hypothesis that GADD45 could have a protective role in
      neuronal injury.

PMID- 9626190
TI  - Increased Mdm2 expression in rat brain after transient middle cerebral artery
      occlusion.
AB  - The negative regulator of p53 transactivation, Mdm2, increased in the ischemic
      territory after 90 minutes of transient middle cerebral artery occlusion in
      spontaneously hypertensive rats compared to sham controls. Increased mdm2 mRNA
      was detected by semiquantitative reverse transcriptase polymerase chain reaction
      by 6 hours of reperfusion in the ipsilateral hemisphere. In situ hybridization
      histochemistry was used to localize increases in mdm2 mRNA which occurred in
      neurons of ischemic cortex and dorsolateral striatum. The number of labeled
      neurons increased by approximately 20-fold and the cells displayed five-fold
      increases of mdm2 mRNA in the cortex. Immunohistochemical staining for Mdm2
      revealed that its mRNA was efficiently translated in the ischemic cortex, but not
      striatum, by 8 to 24 hours of reperfusion. Western blotting confirmed 30- to 40
      fold increases in the full-length protein of 90 kd at these time points without
      evidence of alternative splicing. Because Mdm2 is a negative regulator of the
      apoptosis promoting activity of p53, increased expression of Mdm2 may be a
      component of a repair response in injured neurons, and supports Mdm2 being an
      indicator of DNA damage in the brain early after an ischemic insult in a similar
      way to Gadd45.

PMID- 9626191
TI  - Reoxygenation increases the release of reactive oxygen intermediates in murine
      microglia.
AB  - Respiratory burst activity of murine microglial cells was investigated in vitro
      under normoxic and hypoxic conditions with a chemoluminometric assay. Hypoxia for
      24 hours reduced the release of extracellular reactive oxygen intermediates
      (ROIs), whereas reoxygenation increased the chemoluminescence more than
      sevenfold. Blockade of potassium channels inhibited the increase of oxidative
      burst after reoxygenation, indicating that potassium ions, which were increased
      in the supernatant of hypoxic microglial cells, were involved in this activation
      process. Also, blockade of voltage-gated calcium channels with nifedipine
      attenuated the increased release of ROIs. With fura-2 analysis, it was shown that
      the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase by
      potassium ions was mediated by calcium influx via voltage-gated calcium channels.
      Thus, influx of calcium ions through voltage-gated channels activates the NADPH
      oxidase in microglial cells during reoxygenation. By the increased production of
      ROIs, microglial cells may add to the reperfusion injury after ischemia in vivo.

PMID- 9626192
TI  - Restoring adenine nucleotides in a brain slice model of cerebral reperfusion.
AB  - Tissue adenine nucleotides are depleted during cerebral ischemia, impeding
      recovery after reperfusion. Although prior studies have attempted to prevent the
      initial loss of adenylates, the present study tests the hypothesis that
      stimulating synthesis of adenine nucleotides, through either adenosine kinase or
      adenine phosphoribosyltransferase, would result in significant cerebroprotection.
      To study the effects on neurons and glia directly while avoiding the influence of
      the cerebral vasculature, hippocampal brain slices were used for the model of
      transient ischemia with reperfusion. The standard brain slice insult of brief
      exposure to anoxia with aglycemia was modified based on studies which showed that
      a 30-minute exposure to air with 1 mmol/L glucose produced a stable, moderate
      reduction in ATP during the insult and that, 2 hours after return to normal
      conditions, there was moderate depletion of tissue adenine nucleotides and
      histologic injury. Treatments with 1 mmol/L adenosine, AMP, or adenine were
      equivalent in partially restoring adenine nucleotides. Despite this, only
      adenosine afforded histologic protection, suggesting a protective role for
      adenosine receptors. There also was evidence for metabolic cycling among adenine
      nucleotides, nucleosides, and purines. Adenosine may exert direct
      cerebroprotective effects on neural tissue as well as indirect effects through
      the cerebral vasculature.

PMID- 9626193
TI  - Changes in protein synthesis and calcium homeostasis in the thalamus of
      spontaneously hypertensive rats with focal cerebral ischemia.
AB  - The thalamus has been shown to undergo secondary degeneration after
      cerebrocortical ischemia. However, little is known about the time course of the
      retrograde thalamic degeneration. The present study was designed to investigate
      time-dependent changes in the morphology, protein synthesis and calcium
      metabolism of thalamic neurons in middle cerebral artery (MCA)-occluded
      spontaneously hypertensive stroke-prone rats that showed primary focal ischemia
      in the temporoparietal cortex after permanent occlusion of the left distal MCA.
      In the histologic study by light and electron microscopy, swelling of the nucleus
      and shrinkage of the perikarya were seen in some neurons of the ventroposterior
      (VP) thalamic nucleus on the lesioned side at 5 days after ischemia. At the same
      time, the incorporation of radiolabeled leucine in VP thalamic neurons began to
      decrease significantly with concomitant a decrease in the number of polyribosomes
      in the neurons. Conspicuous 45Ca accumulation was noted at 3 days after ischemia
      and persisted up to 1 month in the VP thalamic nucleus on the lesioned side.
      These findings suggest that the secondary thalamic degeneration after cortical
      infarction starts with disruption of calcium homeostasis in situ at the third day
      after MCA occlusion, followed by a decrease in polyribosomes but not by
      disaggregation of polyribosomes as seen in hippocampal CA1 neurons subjected to
      transient forebrain ischemia.

PMID- 9626194
TI  - Holmes and Watson on 'Sherlock'.

PMID- 9626195
TI  - Cerebral blood flow measurements by near infrared spectrophotometry in
      reflectance mode are valid in neonates.

PMID- 9626196
TI  - Stage 4S neuroblastoma: what makes it special?

PMID- 9626197
TI  - Prognostic significance of age, MYCN oncogene amplification, tumor cell ploidy,
      and histology in 110 infants with stage D(S) neuroblastoma: the pediatric
      oncology group experience--a pediatric oncology group study.
AB  - PURPOSE: Although a high rate of spontaneous regression is observed in infants
      with stage D(S) neuroblastoma (NB), survival is not uniform. To determine the
      prognostic relevance of age at diagnosis, therapy, and tumor biology in infants
      with stage D(S) NB, we reviewed the Pediatric Oncology Group (POG) experience.
      PATIENTS AND METHODS: A review of patients diagnosed with stage D(S) NB
      registered on POG protocols was performed. Survival according to age at
      diagnosis, treatment, and tumor biology was determined. RESULTS: Between 1987 and
      1996, 110 infants with stage D(S) NB had an estimated 3-year survival rate of 85%
      +/- 4%; survival rate was 71% +/- 8% for infants 2 months of age or younger, and
      68% +/- 12%, 44% +/- 33%, and 33% +/- 19% for patients with diploid, MYCN
      amplified, and unfavorable histology tumors, respectively. Survival rates were
      similar for patients who received adjuvant chemotherapy versus those who did not
      (82% +/- 5% v 93% +/- 6%, respectively; P = .187). Furthermore, there was no
      statistical difference in survival rate for patients who underwent complete
      resection of their primary tumor compared with those who underwent partial
      resection or biopsy only (90% +/- 5% v 78% +/- 7%, respectively; P = .083).
      CONCLUSION: Our review confirmed that the survival of infants with stage D(S) NB
      is excellent. However, subsets of patients with poor prognosis can be identified
      by young age and unfavorable biologic factors. More effective therapy is needed
      for the group of stage D(S) infants who show unfavorable clinical and biologic
      features.

PMID- 9626198
TI  - Survival impact of adjuvant tamoxifen on competing causes of mortality in breast
      cancer survivors, with analysis of mortality from contralateral breast cancer,
      cardiovascular events, endometrial cancer, and thromboembolic episodes.
AB  - PURPOSE: This study provides estimates of the effect of tamoxifen treatment on
      mortality from four conditions known to be affected by tamoxifen in women who
      survive their breast cancer: contralateral breast cancer, cardiovascular events,
      endometrial cancer, and thromboembolic events. These estimates are in addition to
      tamoxifen's impact on primary breast cancer mortality. METHODS: The effects of
      tamoxifen were calculated by the use of the published relative risk (RR) rates of
      the four conditions as affected by adjuvant tamoxifen and their application to
      the respective Canadian age-specific mortality rates for the same conditions. The
      final mortality impact of tamoxifen was expressed as net mortality difference
      between users and nonusers of tamoxifen. RESULTS: At 10 years of follow-up, the
      sum of avoided deaths (contralateral breast cancer, cardiovascular events) and
      excess deaths (uterine cancer, thromboembolic episodes) resulted in an overall
      (net) mortality reduction because of tamoxifen use, with 3 to 41 avoided deaths
      per 1,000 tamoxifen-treated patients who were 50 to 80 years of age. With the
      follow-up projected until the age of 90 years, the numbers of avoided late deaths
      attributed to tamoxifen ranged from 38 to 56 per 1,000 patients. CONCLUSION: Our
      calculations that pertain to late breast cancer survivors indicate that there is
      a more substantial mortality reduction as a result of deaths avoided from
      contralateral breast cancer and cardiovascular events, despite the moderately
      increased mortality from endometrial cancer and thromboembolic episodes. The
      overall tamoxifen-associated mortality reduction occurs, in different magnitudes,
      in patients of all ages from 50 to 80 years at diagnosis of the primary breast
      cancer.

PMID- 9626199
TI  - bcl-2 automated and quantitative immunocytochemical assays in breast carcinomas:
      correlation with 10-year follow-up.
AB  - PURPOSE: bcl-2 protein is detectable in human cancers and may be involved in the
      response to antineoplastic drugs or endocrine therapy in breast carcinomas. In a
      previous study, we had developed optimal technical conditions for bcl-2
      immunodetection. The aim of the present report was to determine the prognostic
      significance of bcl-2 expression in breast carinomas by the use of a similar
      immunocytochemical procedure. METHODS: bcl-2 immunocytochemical assays were
      performed on frozen sections by automated immunoperoxidase technique (Ventana)
      and computer-assisted analysis of digitized colored microscopic images (SAMBA) in
      a series of 170 breast carcinomas. The results of automated quantitative
      immunocytochemical assays were correlated with patient follow-up (120 months).
      RESULTS: Intense bcl-2 immunocytochemical expression in tumors (cutpoint, 15%)
      significantly correlated with longer disease-free survival and longer recurrence
      free survival in the entire cohort of patients (P = .028 and P = .035,
      respectively) and also in node-negative subgroups of patients (P = .028 and P =
      .01; Kaplan-Meier long-rank test; NCSS 6.0.1 software). But bcl-2 immunostained
      surfaces (cutpoint, 15%) did not correlate with overall survival. In multivariate
      analysis (proportional hazards regression, Cox model), bcl-2 prognostic
      significance in terms of disease-free survival was only independent of the tumor
      size and grade and histoprognostic index (Nottingham prognostic index [NPI]).
      CONCLUSION: bcl-2 immunohistochemical expression is a significant indicator of
      favorable outcome only in terms of disease-free and local recurrence-free
      survival. However, bcl-2 expression in tumors is an independent weakly prognostic
      indicator in breast carcinomas. bcl-2 immunodetection assessed in optimal
      technical conditions (frozen samples, automation, quantitative analysis, scatter
      diagram cutoffs) may have some limited practical clinical relevance for the
      management of patients with breast carcinomas.

PMID- 9626200
TI  - Phase II trial of paclitaxel and topotecan with granulocyte colony-stimulating
      factor support in stage IV breast cancer.
AB  - PURPOSE: This multicenter phase II trial investigated the efficacy and safety of
      a combination of paclitaxel and topotecan in patients with pretreated metastatic
      breast cancer. Plasma levels of paclitaxel and topotecan were obtained during
      cycle 1 to correlate pharmacokinetic parameters with toxicity. PATIENTS AND
      METHODS: Paclitaxel was administered intravenously (i.v.) at 230 mg/m2 over 3
      hours on day 1 followed by topotecan 1.0 mg/m2 i.v. over 30 minutes on days 1 to
      5. Patients received an abbreviated premedication regimen that consisted of
      ranitidine 50 mg, diphenhydramine 50 mg, and a single 20-mg dose of
      dexamethasone, all administered i.v. 30 minutes before paclitaxel. Granulocyte
      colony-stimulating factor (GCSF) was administered at 5 micrograms/kg/d
      subcutaneously starting on day 6 and continuing until the absolute granulocyte
      count (AGC) was greater than 10,000/microL. Plasma paclitaxel and topotecan
      concentrations were assessed during the first cycle using limited-sampling
      strategies. RESULTS: Seventeen patients were treated. The majority had visceral
      metastases. Four patients experienced neutropenic fever and one had mild
      bronchospasm. Only one partial response (PR) was observed. Nadir AGC correlated
      strongly with both duration of paclitaxel levels greater than 0.05 mumol/L and
      maximum concentration (Cmax) of paclitaxel. CONCLUSION: This regimen does not
      produce a response rate superior to that expected with single-agent paclitaxel at
      doses that do not require growth factor support.

PMID- 9626201
TI  - Long-term prevention of skeletal complications of metastatic breast cancer with
      pamidronate. Protocol 19 Aredia Breast Cancer Study Group.
AB  - PURPOSE: Pamidronate, an aminobisphosphonate, has been shown to lower the risk of
      skeletal complications associated with lytic bone lesions for up to 1 year in
      women with stage IV breast cancer who received chemotherapy. We studied the long
      term effectiveness and safety of continued treatment with intravenous pamidronate
      infusions for up to 2 years. PATIENTS AND METHODS: Three hundred eighty-two women
      with metastatic breast cancer and lytic bone lesions who received chemotherapy
      were randomly assigned to receive either 90 mg of pamidronate or placebo
      intravenously every 3 to 4 weeks in this double-blind, multicenter, parallel
      group trial. Patients were evaluated monthly for 2 years for skeletal
      complications, which included pathologic fractures, need for radiation or surgery
      to treat bone complications, spinal cord compression, and hypercalcemia. Bone
      pain, analgesic use, bone biochemical markers, performance status, quality of
      life, radiologic response in bone, and survival were also evaluated. RESULTS: As
      in the first year of treatment, the proportion of patients with any skeletal
      complication was significantly less for the pamidronate than the placebo group at
      15, 18, 21, and 24 months (P < .001). The proportions of patients with any
      pathologic fracture (i.e., vertebral and nonvertebral fractures), need for
      radiation or surgery to treat bone complications, and hypercalcemia were also
      statistically less for the pamidronate than the placebo group. The median time to
      the first skeletal complication was 13.9 months in the pamidronate-treated women
      and 7.0 months in the placebo group (P < .001). Long-term treatment did not
      result in any unexpected adverse events. Survival did not differ between the two
      groups. CONCLUSION: The risk for osteolytic bone lesion complications in
      metastatic breast cancer was significantly decreased with monthly infusions of 90
      mg of pamidronate, and this effect was maintained for at least 2 years.
      Pamidronate is a useful adjunct to standard chemotherapy in the palliative
      treatment of metastatic breast cancer.

PMID- 9626202
TI  - Family history and treatment outcome in young women after breast-conserving
      surgery and radiation therapy for early-stage breast cancer.
AB  - PURPOSE: To evaluate the safety and efficacy of breast-conserving therapy for
      young women with a family history (FH) suggestive of inherited breast cancer
      susceptibility. MATERIALS AND METHODS: A total of 201 patients aged 36 or younger
      at diagnosis treated with breast-conserving surgery and radiation therapy (> or =
      60 Gy) for early-stage breast cancer were categorized by FH. FH was considered
      positive in 29 patients who, at the time of diagnosis, had a mother or sister
      previously diagnosed with breast cancer before age 50 or ovarian cancer at any
      age. Clinical, pathologic, and demographic variables; sites of first failure;
      disease-free survival; and overall survival (OS) were compared between FH
      positive and -negative groups. Median follow-up time was 11 years. RESULTS:
      Patient and tumor features were similar between those with and without an FH.
      Regression analysis of sites of first failure at 5 years demonstrated a risk
      ratio (RR) of 5.7 for opposite breast cancer for FH-positive patients. Rates of
      local, regional, and distant failure and disease-free survival or OS did not
      differ between FH-positive and -negative patients. Age at diagnosis and Ashkenazi
      heritage were not significantly predictors of patterns of failure. CONCLUSION:
      Breast-conserving surgery combined with radiation therapy is not associated with
      a higher rate of local recurrence, distant failure, or second (non-breast)
      cancers in young women with an FH suggestive of inherited breast cancer
      susceptibility compared with young women without an FH. However, their increased
      risk of opposite breast cancer should be taken into account when considering
      breast conservation as a treatment option.

PMID- 9626204
TI  - Activity of fludarabine in previously treated Waldenstrom's macroglobulinemia: a
      report of 71 cases. Groupe Cooperatif Macroglobulinemie.
AB  - PURPOSE: There is no consensus on the treatment of patients with Waldenstrom's
      macroglobulinemia (WM) who develop primary or secondary resistance to frontline
      therapies. We report our experience on the activity and toxicity of fludarabine
      in 71 patients with WM resistant to prior chemotherapy regimens. PATIENTS AND
      METHODS: From January 1991 to June 1995, 71 patients were included in this
      retrospective study. The median age, median time from diagnosis to treatment,
      median immunoglobulin M (IgM) level, and median number of previous treatments
      were 68 years (range, 42 to 81), 5.9 years (range, 0.6 to 20), 35 g/L (range, 5
      to 126), and two (range, one to four), respectively. RESULTS: Seventy-one
      patients received a median of six courses of fludarabine. Twenty-one (30%)
      responded with a partial response and 50 (70%) were considered as treatment
      failures. Forty-six patients died: 10 in the responder group and 36 in the
      failure group. Twenty-five patients were alive with a median follow-up time of 34
      months. The overall median survival time of all treated patients was 23 months.
      The time to treatment failure was 32 months. The only factor that favorably
      influenced the response to fludarabine was a longer interval between the first
      treatment and the start of fludarabine. Pretreatment factors associated with
      shorter survival in the entire population were hemoglobin level less than 95 g/L
      (P = .02) and platelet count less than 75 x 10(9)/L (P = .02). CONCLUSION: The
      responses rate in this population with a poor prognosis is close to that reported
      in shorter series. Patients with WM who are resistant to alkylating agents should
      be identified early, so that salvage therapy with nucleoside analogs can be
      started without delay.

PMID- 9626203
TI  - Posttransplant lymphoproliferative disorders not associated with Epstein-Barr
      virus: a distinct entity?
AB  - PURPOSE: Organ recipients are at a high risk of posttransplant
      lymphoproliferative disorders (PTLD) as a result of immunosuppressive therapy.
      Most B-cell lymphomas are associated with Epstein-Barr virus (EBV) infection. We
      describe a morphologically and clinically distinct group of PTLD in 11 patients
      that occurred late after organ transplantation and were not associated with EBV.
      PATIENTS AND METHODS: There were seven kidney, three heart, and one liver
      transplant recipients (group I). The clinical manifestations, pathologic
      findings, treatment, and outcome were compared with those in 21 patients with EBV
      associated PTLD treated in our institution (group II). EBV was detected with at
      least two techniques: Epstein-Barr-encoded RNA (EBER) in situ hybridization with
      EBER 1 + 2 probes, Southern blotting, and detection of latent membrane protein 1
      (LMP1) expression by immunohistochemistry. RESULTS: The time between
      transplantation and the diagnosis of lymphoma ranged from 180 to 10,220 days in
      group I (mean, 2,234; median, 1,800) and from 60 to 2,100 days in group II (mean,
      546; median, 180), and was significantly shorter in group II (P = .02). Among 19
      tumors diagnosed within 2 years after the graft, 16 were associated with EBV;
      among 13 tumors diagnosed after more than 2 years, only five were associated with
      EBV. All of the B-cell PTLDs in group I were classified as monomorphic, meeting
      the criteria of B diffuse large-cell lymphoma (B-DLCL) with a component of
      immunoblasts, and genotyping confirmed their monoclonality. Three tumors were T
      cell pleomorphic lymphomas. Tumor sites were mainly bone marrow and lymph nodes.
      Overall median survival was 1 month in group I and 37 months in group II, with
      two patients still alive in group I and nine in group II. The survival time was
      significantly longer in group II (P < .01). CONCLUSION: EBV-negative PTLD may be
      a late serious complication of organ transplantation. Half the tumors observed
      after kidney transplantation in our center were not associated with EBV and
      emerged after more than 5 years, which suggests the number of EBV-negative PTLDs
      in organ recipients might increase with time.

PMID- 9626205
TI  - Risk factors for treatment-related death in elderly patients with aggressive non
      Hodgkin's lymphoma: results of a multivariate analysis.
AB  - PURPOSE: It has been suggested that age is associated with chemotherapy-related
      death in patients with non-Hodgkin's lymphoma (NHL) treated with doxorubicin
      containing chemotherapy. The purpose of this study was to evaluate the relative
      influence of increasing age and other clinical parameters on the occurrence of
      treatment-related death in elderly patients with intermediate- or high-grade NHL
      treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)
      chemotherapy. METHODS: A retrospective study of patients 60 years of age or older
      with intermediate- or high-grade NHL treated with CHOP chemotherapy in a single
      cancer center. The following variables were recorded: age (60 to 69, 70 to 79,
      and 80 to 94 years), histology (Working Formulation [WF] D, E, F, G, and H), Ann
      Arbor stage, B symptoms, extranodal involvement, bulky disease (> 7 cm),
      performance status (Eastern Cooperative Oncology Group [ECOG] scale),
      International Prognostic Index (IPI score), serum lactate dehydrogenase (LDH)
      level and doxorubicin relative dose-intensity (RDI). The relationship between
      these features and treatment-related death was assessed in univariate and
      multivariate logistic regression analysis. RESULTS: From 1982 to 1991, 267
      consecutive patients were treated. Median age was 70 years (range, 60 to 94
      years). There were 35 toxic deaths. Sixty-three percent of the deaths occurred
      after the first cycle. Infection accounted for 82% of the toxic deaths. In the
      univariate analysis, the features associated with an increased risk of toxic
      death were ECOG performance status 2 to 4 (relative risk [RR], 7.82), B symptoms
      (RR, 3.38), diffuse large-cell histology (RR, 3.06), bulky disease (RR, 2.58),
      serum levels of LDH (RR, 2.53), and IPI score (RR, 2.46). The age groups did not
      show significance. In the regression model, performance status 2 to 4 was the
      only independent predictor of treatment-related death (RR, 3.52; 95% confidence
      interval [CI], 2.98 to 4.06). CONCLUSION: Our results show that in elderly
      patients with NHL treated with doxorubicin-based chemotherapy the risk for
      treatment-related death is associated with poor performance status rather than
      with increasing chronologic age.

PMID- 9626206
TI  - Late effects in long-term survivors of high-grade non-Hodgkin's lymphomas.
AB  - PURPOSE: To evaluate long-term survivors of high-grade non-Hodgkin's lymphomas
      (NHLs) for late effects and to attempt to assess the relative contributions of
      the primary treatment modalities to these late effects. PATIENTS AND METHODS: Of
      103 young survivors followed up for 1 to 20 years, 74 patients were interviewed
      and underwent various investigations, and an additional 12 patients were
      interviewed only. Of the 86 patients, 65 had previously suffered from small non
      cleaved-cell lymphoma, 16 from lymphoblastic lymphoma, and five from large-cell
      lymphoma. RESULTS: Left ventricular dysfunction was identified in eight of 57
      (14.0%) patients who had received doxorubicin (DOX) in doses greater than 200
      mg/m2, of whom four were symptomatic and four were asymptomatic. A ninth patient
      required a pacemaker. Of the 86 patients, 23 (26.7%) reported pregnancies, 18 of
      whom had 30 children. Two of the 86 (2.3%) patients developed second cancers.
      Other major late effects included posttransfusion viral hepatitis, eight
      patients; CNS toxicity, two patients; endocrine impairment, 14 patients; vitamin
      B12 deficiency, two patients; esophageal stricture, one patient; urinary tract
      problems, two patients; and musculoskeletal defects, three patients. Major late
      effects occurred in 11 of 21 (52.4%) patients who had received radiation as well
      as chemotherapy, eight of 22 (36.4%) patients who had surgical resections as well
      as chemotherapy, and 17 of 74 (23.0%) patients who had received chemotherapy
      alone. CONCLUSION: The predominant major late effects observed were late cardiac
      toxicity related to DOX therapy and hepatitis C virus infection that presumably
      resulted from blood product transfusions administered before the introduction of
      screening for the hepatitis C virus. Fertility was not greatly impaired, and
      second malignancies were uncommon. No patient had clinically significant
      impairment of growth. Radiation appeared to increase the likelihood of late
      effects.

PMID- 9626207
TI  - bcl-2 protein expression in primary cutaneous large B-cell lymphoma is site
      related.
AB  - PURPOSE: Primary cutaneous large B-cell lymphoma (PCLBCL) that presents on the
      leg has recently been recognized as a distinct disease entity. These lymphomas
      have a reduced disease-free survival and a worse prognosis as compared with the
      more common, morphologically similar PCLBCL that present on the head or trunk.
      Studies in noncutaneous diffuse large B-cell lymphomas suggest a relationship
      between the expression of bcl-2 protein and clinical behavior. In the present
      study, we investigated whether these two groups of PCLBCL differ in the
      expression of bcl-2 protein and the presence of t(4;18), known as one of the
      causes of bcl-2 overexpression. PATIENTS AND METHODS: Paraffin sections from
      pretreatment biopsies of 14 PCLBCLs of the head or trunk and nine PCLBCLs of the
      legs were investigated for expression of bcl-2 protein using
      immunohistochemistry, and for the presence of the 14;18 translocation using
      polymerase chain reaction (PCR) amplification with primers against both the major
      breakpoint region (mbr) and the minor cluster region (mcr) of bcl-2. For reasons
      of comparison, nine secondary cutaneous large B-cell lymphomas (SCLBCLs) were
      also studied. RESULTS: Expression of bcl-2 protein was found in all nine PCLBCLs
      of the leg and in all nine SCLBCLs, but not in any of the 14 PCLBCLs on the head
      and trunk. The t(14;18) was only detected in two of seven SCLBCLs, but not in the
      five PCLBCLs of the leg or the eight PCLBCLs on the head or trunk studied.
      CONCLUSION: The striking differences in bcl-2 expression between PCLBCL of the
      head or trunk and PCLBCL on the leg suggest that bcl-2 expression is site-related
      and may contribute to the different clinical behavior between these two groups of
      lymphomas. In addition, they underscore that PCLBCL on the head and trunk and
      PCLBCL on the leg are distinct disease entities, as recently recognized in the
      European Organization for Research and Treatment of Cancer (EORTC) classification
      for primary cutaneous lymphomas.

PMID- 9626208
TI  - Role of daunorubicin in the induction therapy for adult acute myeloid leukemia.
AB  - PURPOSE: To evaluate the relationship of total-dose of daunorubicin (DNR) to the
      induction therapy and treatment outcome, we have administered individualized
      doses of DNR during induction treatment to patients with acute myelogenous
      leukemia (AML). PATIENTS AND METHODS: Ninety-two previously untreated adult
      patients with AML who entered our hospital were analyzed for the dose of DNR
      required to achieve complete remission (CR), the CR rate, disease-free survival
      (DFS), and overall survival (OS). Induction therapy consisted of DNR 40 mg/m2
      daily intravenously from day 1 until the marrow was hypoplastic, cytarabine (Ara
      C), prednisolone (PRD), and/or 6-thioguanine (6-TG). RESULTS: Eighty-three of 92
      patients with adult AML were assessable for this study. Sixty-three (76%)
      patients achieved CR. Fifty-two of 63 CR patients achieved the CR in the first
      course of induction therapy, and 11 patients required the second course of
      induction therapy. The 5-year and 10-year DFS rates were 31.2% and 5-year and 10
      year OS rates were 45.1% and 42.3%, respectively. The median total dose of DNR in
      the induction therapy was 280 mg/m2 (120 to 480 mg/m2). DNR dose did not
      influence the response to therapy and was not influenced by the initial WBC count
      or French-American-British (FAB) system classification. CONCLUSION: These results
      indicated that when the dose was linked to observed tumor response, the optimal
      dose of DNR in the induction therapy was approximately 280 mg/m2 (40 mg/m2 for 7
      days), which is greater than the conventional dose of 40 to 60 mg/m2 for 3 days.

PMID- 9626209
TI  - CD34+CD33- cells influence days to engraftment and transfusion requirements in
      autologous blood stem-cell recipients.
AB  - PURPOSE: To evaluate the reliability of CD34/CD33 subset enumeration as a
      predictor of hematopoietic repopulating potential in autologous blood stem-cell
      transplantation and to determine which patient and treatment-related factors
      affect the timing, quantity, and type of blood stem cells mobilized. PATIENTS AND
      METHODS: We analyzed blood stem-cell collections from 410 consecutive cancer
      patients who received mobilization therapy and evaluated factors, including CD34+
      subset quantities, that might influence engraftment kinetics and transfusion
      requirements in autologous blood stem-cell recipients. RESULTS: The majority of
      patients (97%) mobilized CD34+33- cells, which were usually collected in the
      greatest quantity on the first day of apheresis. Patients who received only
      growth factor mobilized the highest percentage of CD34+33- cells. Extensive prior
      chemotherapy limited the collection of CD34+33- cells. In addition to patient
      diagnosis (P < .006) and total CD34+ cell dose (P = .0001), CD34+33- cell dose (P
      < .005) and percentage of CD34+33- cells (P < .005) were identified as
      independent factors significantly predictive of engraftment kinetics. CD34+33-
      cell dose (R2 < or = .177; P < .0001) was a strong and the only significant
      predictor of RBC and platelet transfusion requirements. Furthermore, independent
      of the total CD34+ cell dose, as the CD34+33- cell dose increased, days to
      neutrophil recovery, days to platelet recovery, and transfusion requirements
      decreased. CONCLUSION: These findings show that CD34+33- cells are readily
      collected in most cancer patients and significantly influence engraftment
      kinetics and transfusion requirements in autologous blood stem-cell recipients.
      CD34+33- cell quantity of the blood stem-cell graft appears to be a more reliable
      predictor of hematopoietic recovery rates than total CD34+ cell quantity in this
      setting.

PMID- 9626210
TI  - Unknown primary tumors metastatic to liver.
AB  - PURPOSE: The objectives of this study were to identify prognostic factors for
      unknown primary tumor (UPT) patients with hepatic metastases, determine the
      common primary tumors identified, assess the yield of specific diagnostic
      studies, and evaluate the impact of therapy on survival. PATIENTS AND METHODS:
      The 1,522 patients analyzed were referred from January 1, 1987 through June 30,
      1995. Clinical data from these patients were entered into a computerized database
      for storage, retrieval, and analysis. Survival was measured from the time of
      diagnosis; survival distribution was estimated by the product limit method.
      Multivariate survival analyses were performed by proportional hazards regression.
      RESULTS: Five hundred UPT patients had liver metastases. Primary tumors, usually
      lung, colorectal, or pancreatic neoplasms, were identified in 135 patients (27%).
      The remaining 365 unknown primary carcinoma (UPC) patients with liver involvement
      had a higher death rate than those without liver involvement (hazards ratio,
      1.63; P < .0001). Neuroendocrine carcinoma patients had a lower death rate than
      patients without this histology (hazards ratio, 0.29; (P < .0001). Two hundred
      sixteen of 365 patients with UPC and liver metastases received chemotherapy.
      Chemotherapy-treated patients had a lower death rate than those who were not
      treated with chemotherapy (hazards ratio, 0.52; P < .0001). The effect of
      chemotherapy was most pronounced in patients with adenocarcinoma. CONCLUSION:
      Hepatic metastases in UPC patients portend a generally poor prognosis. However,
      subsets of patients with more favorable outcomes can be identified by available
      clinical and pathologic data. Chemotherapy may be beneficial for the large subset
      of UPC patients with adenocarcinoma that involves the liver.

PMID- 9626211
TI  - Analytical decision model for the cost-effective management of solitary pulmonary
      nodules.
AB  - PURPOSE AND METHODS: Multiple strategies are currently being used to manage
      patients who present with indeterminate solitary pulmonary nodules (SPN). We have
      used decision-analysis models to assess the cost-effectiveness of various
      strategies for the diagnosis and management of SPN. Four decision strategies were
      compared: a wait and watch strategy, a surgery strategy, a computed tomography
      (CT)-based strategy, and a CT-plus-positron emission tomography (PET) strategy.
      An incremental cost-effectiveness ratio (ICER) was used to compare all strategies
      to the wait and watch strategy. RESULTS: A CT-plus-PET strategy was the most cost
      effective over a large pretest likelihood (probability of having a malignant
      nodule), with a range of 0.12 to 0.69. Furthermore, within this likelihood range,
      the potential cost savings of using the CT-plus-PET strategy over the CT strategy
      ranged from $91 to $2,200 per patient. This translates to a yearly national
      savings of approximately $62.7 million. CONCLUSION: Decision-analysis modeling
      indicates the potential cost-effectiveness of [18F]2-fluoro-2-deoxy-D-glucose
      (FDG)-PET in the management of SPN. Furthermore, the decision trees developed can
      be used to model various features of the management of SPN, including modeling
      the cost-effectiveness of other newly emerging technologies.

PMID- 9626212
TI  - Phase III study of intensive weekly chemotherapy with recombinant human
      granulocyte colony-stimulating factor versus standard chemotherapy in extensive
      disease small-cell lung cancer. The Japan Clinical Oncology Group.
AB  - PURPOSE: To evaluate the therapeutic significance of cisplatin, vincristine,
      doxorubicin, and etoposide (CODE) plus granulocyte colony-stimulating factor (G
      CSF) compared with cyclophosphamide, doxorubicin, and vincristine, alternating
      with cisplatin and etoposide (CAV/PE) for extensive-disease (ED) small-cell lung
      cancer (SCLC). PATIENTS AND METHODS: Two hundred twenty-seven patients were
      randomized. CODE consisted of cisplatin 25 mg/m2 weekly for 9 weeks; vincristine
      1 mg/m2 on weeks 1, 2, 4, and 6; and doxorubicin 40 mg/m2 and etoposide 80 mg/m2
      for 3 days on weeks 1, 3, 5, 7, and 9. G-CSF 50 micrograms/m2 was administered on
      the days when chemotherapy was not administered. CAV/PE consisted of
      cyclophosphamide 800 mg/m2; doxorubicin 50 mg/m2; and vincristine 1.4 mg/m2 on
      day 1, which alternated every 3 weeks with cisplatin 80 mg/m2 on day 1 and
      etoposide 100 mg/m2 on days 1 to 3. RESULTS: Overall response rates were 77% for
      the CAV/PE arm and 84% for the CODE arm respectively (15% complete response in
      both arms). The median survival times were 10.9 months in the CAV/PE arm and 11.6
      months in the CODE arm (P = .1034). The achieved dose-intensity for CODE was
      approximately twice that for CAV/PE for those drugs common to both arms. The
      incidence of leukopenia did not differ between the two arms, but anemia and
      thrombocytopenia had a significantly higher incidence in the CODE arm. Four
      treatment-related deaths from neutropenic fever occurred in the CODE arm.
      CONCLUSION: The CODE group had a similar median survival to the CAV/PE group. It
      does not appear that CODE is a useful approach to improve survival in ED SCLC.

PMID- 9626213
TI  - Randomized study of paclitaxel-cisplatin versus cisplatin-teniposide in patients
      with advanced non-small-cell lung cancer. The European Organization for Research
      and Treatment of Cancer Lung Cancer Cooperative Group.
AB  - PURPOSE: To compare two cisplatin based chemotherapy schedules in patients with
      advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 332
      patients with advanced NSCLC were randomized to receive cisplatin 80 mg/m2 on day
      1 either in combination with teniposide 100 mg/m2 on days 1, 3, and 5 (arm A) or
      paclitaxel 175 mg/m2 by 3-hour infusion on day 1 (arm B); cycles were repeated
      every 3 weeks. RESULTS: Fifteen patients were ineligible; patient characteristics
      were well balanced between the two arms: 71% were male, 71% had less than 5%
      weight loss, 89% had a World Health Organization (WHO) performance status of 0 to
      1, 51% had adenocarcinoma, and 61% had stage IV disease. Hematologic toxicity was
      significantly more severe in arm A (leukopenia, neutropenia, and thrombocytopenia
      grade 3 or 4: 66% v 19%, 83% v 55%, 36% v 2% in arms A and B, respectively),
      which resulted in more febrile neutropenia (27% v 3% in arms A and B,
      respectively), dose reductions, and treatment delays. There were a total of nine
      toxic deaths, six due to neutropenic sepsis: five in arm A and one in arm B. In
      contrast, arthralgia/myalgia (grade 2 or 3, 4% v 17%), peripheral neurotoxicity
      (grade 2 or 3, 6% v 29%), and hypersensitivity reactions (1% v 7%, all grades)
      were significantly more frequent in arm B. The frequency and severity of other
      toxicities were comparable between the two arms. Responses were one complete and
      44 partial on arm A (28%) and two complete and 61 partial (41%) on arm B (P =
      .018). There was no significant difference in survival, with median and 1-year
      survivals 9.9 versus 9.7 months and 41% versus 43%, respectively in arm A and B.
      Progression-free survival was 4.9 and 5.4 months in arm A and B, respectively.
      Selected centers participated in a quality-of-life (QoL) assessment, which was
      performed by the European Organization for Research and Treatment of Cancer
      (EORTC) QLQ-C30 and LC-13 administered at baseline and every 6 weeks thereafter.
      Arm B achieved a better score at week 6 for emotional, cognitive and social
      functioning, global health status, fatigue, and appetite loss, which was lost at
      12 weeks. In conclusion, arm B appears superior to arm A with regard to response
      rate, side effects, and QoL. CONCLUSION: Although survival was not improved, arm
      B offers a better palliation for advanced NSCLC patients than arm A.

PMID- 9626214
TI  - Lymph node staging in non-small-cell lung cancer with FDG-PET scan: a prospective
      study on 690 lymph node stations from 68 patients.
AB  - PURPOSE: To compare the accuracy of computed tomography-(CT) scan and the
      radiolabeled glucose analog 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission
      tomography (PET) visually correlated with CT (PET + CT) in the locoregional lymph
      node (LN) staging of non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS:
      Sixty-eight patients with potentially operable NSCLC underwent thoracic CT, PET,
      and invasive surgical staging (ISS). Imaging studies were read prospectively and
      blinded to the surgical and pathologic data. A five-point visual scale was used
      for the interpretation of LNs on PET. Afterwards, with knowledge of the
      pathology, the relationship between standardized uptake values (SUVs) and the
      presence of metastasis in LNs was explored in a receiver operating characteristic
      (ROC) analysis, and the likelihood ratios (LRs) for SUVs of LNs were determined.
      RESULTS: ISS was available for 690 LN stations. CT correctly identified the nodal
      stage in 40 of 68 patients (59%), with understaging in 12 patients and
      overstaging in 16 patients. PET + CT was accurate in 59 patients (87%), with
      understaging in five patients and overstaging in four patients. In the detection
      of locally advanced disease (N2/N3), the sensitivity, specificity, and accuracy
      of CT were 75%, 63%, and 68%, respectively. For PET + CT, this was 93%, 95%, and
      94% (P = .0004). In the ROC curve, the best SUV threshold to distinguish benign
      from malignant LNs was 4.40. The analysis with this SUV threshold was not
      superior to the use of a five-point visual scale. The LR of a SUV less than 3.5
      in an LN was 0.152; for a SUV between 3.5 and 4.5, it was 3.157; and for a SUV
      greater than 4.5, it was 253.096. CONCLUSION: PET + CT is significantly more
      accurate than CT alone in LN staging of NSCLC. A five-point visual scale is as
      accurate as the use of an SUV threshold for LNs in the distinction between benign
      and malignant nodes. The very high negative predictive value of mediastinal PET
      could reduce the need for mediastinal ISS in NSCLC substantially.

PMID- 9626215
TI  - Phase I trial of Marimastat, a novel matrix metalloproteinase inhibitor,
      administered orally to patients with advanced lung cancer.
AB  - PURPOSE: This phase I study was performed to evaluate the safety and
      pharmacokinetics of escalating doses of Marimastat (British Biotech, Inc, Oxford,
      United Kingdom) in patients with advanced malignancies and to determine the phase
      II recommended dose to be used in subsequent studies. PATIENTS AND METHODS: A
      standard phase I design was used in this study, in which consecutive groups of
      three patients were treated with escalating doses of the study drug. Marimastat
      was administered orally at 25, 50, or 100 mg twice daily to consecutive groups of
      patients with advanced lung cancer. An additional three patients were added at
      the highest dose studied (100 mg orally twice daily) to assess whether the
      inflammatory polyarthitis observed at that dose level can be prevented by a
      concurrent administration of nonsteroidal antiinflammatory drugs (NSAIDS) and/or
      low-dose corticosteroids. Blood was drawn for safety monitoring, pharmacokinetic
      analysis, and plasma levels of metalloproteinase (MMP)-2 and MMP-9 (determined by
      zymography). A total of 12 patients were studied. RESULTS: The most significant
      toxicity at the highest dose studied (100 mg orally twice daily) was a
      symptomatic inflammatory polyarthritis that persisted for up to 8 weeks after
      discontinuation of the study drug and was dose-limiting. The estimated plasma
      elimination half-life of Marimastat was 4 to 5 hours. The mean maximum
      concentration (Cmax) at a reasonably well-tolerated dose (50 mg orally twice
      daily) was 196 ng/mL and was reached within 1 to 2 hours (Tmax) after
      administration. Areas under the curve (AUC) tended to correlate with the dose of
      Marimastat. Zymographic analysis of peripheral-blood ratios of activated
      proenzymatic forms of MMP-2 and -9 did not show any consistent patterns of change
      in MMP levels or in a degree of their activation during the course of treatment.
      CONCLUSION: Marimastat was well absorbed from the gastrointestinal tract, with
      high levels of the study drug detected in plasma within hours after drug
      administration. Plasma concentrations of Marimastat achieved at dose levels 2 and
      3 (50 mg and 100 mg orally twice daily) were substantially higher than those
      required for MMP inhibition in vitro. The dose-limiting toxicity (DLT) was severe
      inflammatory polyarthritis, which seemed to be a cumulative toxicity.

PMID- 9626216
TI  - Phase I study of vinorelbine, cisplatin, and concomitant thoracic radiation in
      the treatment of advanced chest malignancies.
AB  - PURPOSE: The cisplatin-vinorelbine regimen has superior activity in advanced non
      small-cell lung cancer (NSCLC). We conducted a phase I trial to identify the
      maximum-tolerated dose (MTD) and dose-limiting toxicities (DLTs) of this regimen
      with concomitant thoracic radiation (RT) in patients with advanced chest
      malignancies. PATIENTS AND METHODS: Patients with advanced chest malignancies
      that required RT were enrolled onto this phase I study of standard chest
      radiation (30 daily 2-Gy fractions for a total of 60 Gy) and concurrent
      chemotherapy with cisplatin starting at 100 mg/m2 every 3 weeks and vinorelbine
      starting at 20 mg/m2/wk. RESULTS: Thirty-seven patients were treated on this
      study. Two of three patients treated at the maximum-administered dose of
      cisplatin 100 mg/m2 per cycle and vinorelbine 25 mg/m2/wk experienced acute DLT
      (neutropenia), which required deescalation. The dose level of cisplatin 100 mg/m2
      and vinorelbine 20 mg/m2/wk, although tolerated acutely, produced delayed
      esophagitis, which proved dose-limiting. The recommended phase II dose was
      cisplatin 80 mg/m2 every 3 weeks and vinorelbine 15 mg/m2 given 2 of every 3
      weeks with concomitant chest RT. CONCLUSION: Concomitant chemoradiotherapy with
      cisplatin and vinorelbine is feasible. The recommended phase II dose is cisplatin
      80 mg/m2 every 3 weeks with vinorelbine 15 mg/m2 given twice over 3 weeks on a
      day 1/day 8 schedule. Esophagitis is the DLT, with neutropenia occurring at
      higher dose levels. A Cancer and Leukemia Group B (CALGB) phase II trial is
      currently underway to evaluate further the efficacy and toxicities of this
      regimen in unresectable stage III NSCLC.

PMID- 9626217
TI  - Phase I trial of docetaxel administered by weekly infusion in patients with
      advanced refractory cancer.
AB  - PURPOSE: Docetaxel is a highly active antineoplastic agent; however, grade IV
      leukopenia occurs in the large majority of patients treated with a dose of 100
      mg/m2 every 3 weeks. Recent experience with weekly paclitaxel has demonstrated a
      bone marrow-sparing effect when a weekly administration schedule is used. We
      investigated a weekly schedule of docetaxel in an attempt to alter the toxicity
      profile and improve the therapeutic index. PATIENTS AND METHODS: Thirty-eight
      patients with advanced, refractory malignancy entered this phase I trial between
      October 1996 and June 1997. Docetaxel was administered weekly for 6 consecutive
      weeks, followed by 2 weeks without treatment. Sequential cohorts of patients were
      treated at the following dose levels: 20, 25, 30, 36, 43, and 52 mg/m2. Patients
      were reevaluated after one course (8 weeks); patients with objective response or
      stable disease continued treatment for a maximum of four courses or until disease
      progression. RESULTS: Thirty-five patients completed at least one course of
      therapy. Myelosuppression was not a dose-limiting toxicity (DLT) at any of the
      doses tested. Only five episodes of grade III leukopenia occurred (14% of
      patients, 2% of doses), and no grade IV leukopenia was produced. No grade III or
      IV thrombocytopenia or anemia was observed. Grade III fatigue and asthenia were
      observed in all three patients treated at 52 mg/m2/wk and in two of 10 at 43
      mg/m2/wk. Other grade III toxicity included acral erythema (n = 1), neuropathy (n
      = 1), peripheral edema (n = 1), and diarrhea (n = 1). The DLTs of this docetaxel
      schedule are fatigue and asthenia. Although the maximum-tolerated dose by
      definition of this study was 43 mg/m2/wk, we selected 36 mg/m2/wk for ongoing
      phase II studies. CONCLUSION: The toxicity profile of docetaxel is markedly
      altered when the drug is administered by a weekly schedule. Myelosuppression is
      mild and uncommon. Fatigue and asthenia are the DLTs; other nonhematologic
      toxicities, which included peripheral edema and neuropathy, are uncommon, and the
      arthralgia/myalgia syndrome was not observed. Weekly administration of docetaxel
      may provide a better tolerated, efficacious use of this drug; further
      investigation of weekly docetaxel as a single agent and in combination regimens
      is warranted.

PMID- 9626218
TI  - Phase I trial of a human-mouse chimeric anti-disialoganglioside monoclonal
      antibody ch14.18 in patients with refractory neuroblastoma and osteosarcoma.
AB  - PURPOSE: To evaluate the toxicity, immunogenicity, and pharmacokinetics of a
      human-mouse chimeric monoclonal antibody (mAb) ch 14.18 directed against
      disialoganglioside (GD2) and to obtain preliminary information on its clinical
      efficacy, we conducted a phase I trial in 10 patients with refractory
      neuroblastoma and one patient with osteosarcoma. PATIENTS AND METHODS: Eleven
      patients were entered onto this phase I trial. They received 20 courses of mAb ch
      14.18 at dose levels of 10, 20, 50, 100, and 200 mg/m2. Dose escalation was
      performed in cohorts of three patients; intrapatient dose escalation was also
      permitted. RESULTS: The most prevalent toxicities were pain, tachycardia,
      hypertension, fever, and urticaria. Most of these toxicities were dose-dependent
      and rarely noted at dosages of 20 mg/m2 and less. Although the maximum-tolerated
      dose was not reached in this study, clinical responses were observed. These
      included one partial (PR) and four mixed responses (MRs) and one stable disease
      (SD) among 10 assessable patients. Biologic activity of ch 14.18 in vivo was
      shown by binding of ch 14.18 to tumor cells and complement-dependent cytotoxicity
      of posttreatment sera against tumor target cells. An anti-ch 14.18 immune
      response was detectable in seven of 10 patients studied. CONCLUSION: In summary,
      with the dose schedule used, ch 14.18 appears to be clinically safe and
      effective, and repeated mAb administration was not associated with increased
      toxicities. Further clinical trials of mAb ch 14.18 in patients with
      neuroblastoma are warranted.

PMID- 9626219
TI  - Phase I and pharmacokinetic study of KRN8602 alone and with filgrastim in
      patients with advanced cancer.
AB  - PURPOSE: To determine the recommended dose, toxicity profile, and
      pharmacokinetics of KRN8602 (MX2-hydrochloride), a novel morpholino anthracycline
      with potent cytotoxicity against anthracycline-sensitive and resistant
      experimental tumors in vitro and in vivo. PATIENTS AND METHODS: KRN8602 was
      administered alone in increasing doses to patients with advanced cancer or high
      grade gliomas until dose-limiting toxicity (DLT) was observed in three or more of
      five patients treated in a dose level. Because neutropenia was dose limiting,
      further escalation was investigated with filgrastim support. RESULTS: Fifty-six
      assessable patients completed at least one cycle of chemotherapy. The recommended
      dose of KRN8602 alone was 40 mg/m2. Dose escalation was limited by neutropenia.
      The recommended dose of KRN8602 with filgrastim was 70 mg/m2, and limiting
      toxicities were neutropenia, diarrhea, and vomiting. The most commonly
      experienced nonhematologic toxicity was nausea and vomiting. Alopecia and
      mucositis were infrequent and mild. Pharmacokinetic parameters showed substantial
      variation, although the area under the plasma concentration-time curve (AUC) and
      maximum concentration both increased with dose. There was no relationship between
      pharmacokinetic parameters and toxicity. CONCLUSION: KRN8602 at doses of 40 mg/m2
      when administered alone and 70 mg/m2 when administered with filgrastim appeared
      to be manageable. The major DLTs were neutropenia and, at higher doses, diarrhea
      and vomiting. The efficacy of this drug is currently being tested in phase II
      studies.

PMID- 9626220
TI  - Phase I study of paclitaxel in patients with recurrent malignant glioma: a North
      American Brain Tumor Consortium report.
AB  - PURPOSE: To determine the maximum-tolerated dose (MTD) of paclitaxel administered
      as a 3-hour infusion in patients with recurrent malignant glioma. PATIENTS AND
      METHODS: Patients were stratified by starting dose of paclitaxel and concurrent
      anticonvulsant (AC) use and were treated in cohorts of three patients. The
      starting dose was 240 mg/m2 administered intravenously with escalations of 30
      mg/m2 until the MTD was established. Pharmacokinetic data were obtained for each
      patient for the first infusion. Tumor response was assessed at 6-week intervals
      and treatment was continued until documented tumor progression, unacceptable
      toxicity, or a total of 12 paclitaxel infusions. RESULTS: From April 1995 to
      December 1996, 34 patients were treated; 27 patients in the AC group and seven
      patients in the non-AC group. The MTD for patients who received ACs was
      established at 360 mg/m2 and the dose-limiting toxicity (DLT) was central
      neurotoxicity, characterized as transient encephalopathy and seizures. In
      contrast, the MTD for patients who did not receive ACs was 240 mg/m2, and
      myelosuppression, gastrointestinal toxicity, and fatigue were the DLTs.
      Pharmacokinetic data confirmed that the plasma drug levels and clearance rates
      were similar for patients in both groups at the respective dose levels that
      produced DLTs. CONCLUSION: The pharmacokinetics of paclitaxel are altered by ACs,
      and significantly larger doses of the drug can be administered to patients with
      brain tumors on AC therapy. The toxicity profile is different for patients on AC
      therapy treated at these higher doses. A phase II study has been initiated that
      uses a dose of 330 mg/m2 for patients on AC therapy and 210 mg/m2 for patients
      not on AC therapy.

PMID- 9626221
TI  - Effects of radiation and chemotherapy on cognitive function in patients with high
      grade glioma.
AB  - PURPOSE: The effect of radiotherapy on the long-term cognitive performance of
      patients treated for intracranial neoplasm is a major concern to clinicians and
      patients, particularly as long-term survival or cure is possible for a small
      minority of patients. To assess the effects of cranial radiotherapy and
      chemotherapy on the cognitive performance of high-grade glioma patients, we
      analyzed cognitive performance data collected in a series of prospective clinical
      trials. METHODS: We studied 701 high-grade brain tumor patients entered onto two
      consecutive North Central Cancer Treatment Group (NCCTG) randomized treatment
      trials designed to compare radiotherapy and carmustine (BCNU) versus radiotherapy
      and 1-(2-chloroethyl)-3(2,6 dioxo-l-piperidyl)-1-nitrosource a (PCNU) (first
      trial) and radiotherapy and BCNU and interferon alfa (IFN) versus radiotherapy
      and BCNU (second trial). Folstein Mini-Mental Status Exam (MMSE) score and
      Eastern Cooperative Oncology Group (ECOG) performance score (PS) recorded at
      baseline and 6, 12, 18, and 24 months were analyzed to assess cognitive and
      physical function over time. Patients who did not demonstrate tumor progression
      within 60 days of the assessment time were considered nonprogressors at that
      evaluation. A loss of greater than 3 points on the MMSE was considered
      significant deterioration. RESULTS: The number of patients who experienced a
      greater than 3-point decrease in MMSE from baseline was 13 of 119 nonprogressors
      (10.9%; 95% confidence interval [CI], 6.3% to 18.9%) at 6 months, three of 54
      nonprogressors (5.5%; 95% CI, 0.5% to 12.8%) at 12 months, three of 30
      nonprogressors (10%; 95% CI, 2.1% to 26.5%) at 18 months, and four of 22
      nonprogressors (18.2%; 95% CI, 5.2% to 40.3%) at 24 months. The CIs at all times
      overlapped, which indicates no statistically significant increase in the
      percentage of patients who experienced a significant decrease in their MMSE
      score. Patients who demonstrated a significant decrease in their MMSE score were
      significantly older than those who did not (P = .0017) at 6 months and remained
      so throughout follow-up; moreover, they had a significantly shorter time to
      progression and death. ECOG PS was strongly negatively correlated with MMSE score
      throughout the study, and MMSE score at all time intervals was correlated with
      baseline PS. CONCLUSION: In this population of glioma patients who received
      radiotherapy, there is no clear trend to cognitive worsening. Factors such as
      older age, poorer PS, and subclinical tumor progression may be more significant
      factors in those patients who did demonstrate a significant cognitive decline.

PMID- 9626222
TI  - Iodine-131-labeled antitenascin monoclonal antibody 81C6 treatment of patients
      with recurrent malignant gliomas: phase I trial results.
AB  - PURPOSE: To determine the maximum-tolerated dose (MTD) of iodine 131 (131I)
      labeled 81C6 monoclonal antibody (mAb) in brain tumor patients with surgically
      created resection cavities (SCRCs) and to identify any objective responses to
      this treatment. METHODS: In this phase I trial, eligible patients were treated
      with a single injection of 131I-labeled 81C6. Cohorts of three to six patients
      were treated with escalating dosages of 131I (starting dose of 20 mCi with a 20
      mCi escalation in subsequent cohorts) administered through an Ommaya reservoir in
      the SCRC. Patients were followed up for toxicity and response until death or for
      a minimum of 1 year after treatment. The SCRC patients, who were previously
      irradiated, were followed up without additional treatment unless progressive
      disease was identified. RESULTS: We administered 36 treatments of 131I doses up
      to 120 mCi to 34 previously irradiated patients with recurrent or metastatic
      brain tumors. Dose-limiting toxicity was reached at 120 mCi and was limited to
      neurologic or hematologic toxicity. None of the patients treated with less than
      120 mCi developed significant neurologic toxicity; one patient developed major
      hematologic toxicity (MHT). The estimated median survival for patients with
      glioblastoma multiforme (GBM) and for all patients was 56 and 60 weeks,
      respectively. CONCLUSION: The MTD for administration of 131I-labeled 81C6 into
      the SCRCs of previously irradiated patients with recurrent primary or metastatic
      brain tumors was 100 mCi. The dose-limiting toxicity was neurologic toxicity. We
      are encouraged by the minimal toxicity and survival in this phase I trial.
      Radiolabeled mAbs may improve the current therapy for brain tumor patients.

PMID- 9626223
TI  - Fractionated high-dose-rate brachytherapy in primary carcinoma of the
      nasopharynx.
AB  - PURPOSE: A growing body of data suggests that local control in nasopharyngeal
      cancer (NPC) is related to the radiation dose administered. We conducted a single
      institution study of high-dose radiotherapy (RT), which incorporated high-dose
      rate (HDR) brachytherapy (BT). These results were analyzed together with data
      obtained from controls who did not receive BT. PATIENTS AND METHODS: The BT group
      comprised 42 consecutive patients of whom 29 patients were staged according to
      the tumor, node, metastasis system as T1 through 3, 13 patients were T4, and 34
      patients were N+ disease. BT was administered on an outpatient basis by means of
      a specially designed flexible nasopharyngeal applicator, and the dose
      distributions were optimized. Treatment for T1 through 3 tumors comprised 60 Gy
      of external-beam radiotherapy (ERT) followed by six fractions of 3 Gy BT (two
      fractions per day). Patients with parapharyngeal tumor extension and/or T4 tumors
      received 70 Gy ERT and four fractions of 3 Gy BT. The no-BT group consisted of
      all patients treated from 1965 to 1991 (n = 109), of whom 82 patients had stages
      T1 through 3, 27 patients had T4, and 80 patients had N+ disease. Multivariate
      Cox proportional hazards analyses were performed by using the end points time to
      local failure (TTLF), time to distant failure (TTDF), disease-free survival
      (DFS), cause-specific survival (CSS), and the prognostic factors age, tumor
      stage, node stage, and grade. Because the overall treatment time varied
      substantially in the no-BT group, the dependence of local failure (LF) on the
      physical dose as well as the biologic effective dose (BED) corrected for the
      overall treatment time (OTT) (BEDcor10) was studied. RESULTS: The BT group had a
      superior 3-year local relapse-free rate (86% v 60%; univariate analysis, P =
      .004). Multivariate analysis showed hazards ratios for BT versus no-BT of 0.24
      for TTLF (P = .003), 0.35 for TTDF (P = .038), 0.31 for DFS (P < .001), and 0.44
      for CSS (P = .01). The best prognostic group consisted of patients with T1
      through 3, N0 through 2b tumors treated with BT who attained a 5-year TTLF of 94%
      and CSS of 91%. In contrast, the worst prognostic group, i.e., 5-year TTLF of 47%
      and CSS of 24%, was composed of patients with T4 and/or N2c through 3 tumors who
      did not receive BT. CONCLUSION: High doses of radiation (73 to 95 Gy) can be
      administered to patients with NPC with minimal morbidity by means of optimized
      HDR-BT. The use of a BT boost proved to be of significant benefit, particularly
      in patients with T1 through 3, N0 through 2b disease. The steep dose-effect
      relationship seen for the physical dose and the BEDcor10 indicates that the
      results are dose related. The analysis has identified a poor prognostic group in
      whom treatment intensification with chemotherapy (CHT) is indicated.

PMID- 9626224
TI  - Adenovirus-mediated p53 gene transfer in patients with advanced recurrent head
      and neck squamous cell carcinoma.
AB  - PURPOSE: Standard therapies of head and neck squamous cell carcinoma (HNSCC)
      often cause profound morbidity and have not significantly improved survival over
      the last 30 years. Preclinical studies showed that adenoviral vector delivery of
      the wild-type p53 gene reduced tumor growth in mouse xenograft models. Our
      purpose was to ascertain the safety and therapeutic potential of adenoviral (Ad)
      p53 in advanced HNSCC. PATIENTS AND METHODS: Patients with incurable recurrent
      local or regionally metastatic HNSCC received multiple intratumoral injections of
      Ad-p53, either with or without tumor resection. Patients were monitored for
      adverse events and antiadenoviral antibodies, tumors were monitored for response
      and p53 expression, and body fluids were analyzed for Ad-p53. RESULTS: Tumors of
      33 patients were injected with doses of up to 1 x 10(11) plaque-forming units
      (pfu). No dose-limiting toxicity or serious adverse events were noted. p53
      expression was detected in tumor biopsies despite antibody responses after Ad-p53
      injections. Clinical efficacy could be evaluated in 17 patients with
      nonresectable tumors: two patients showed objective tumor regressions of greater
      than 50%, six patients showed stable disease for up to 3.5 months, and nine
      patients showed progressive disease. One resectable patient was considered a
      complete pathologic response. Ad-p53 was detected in blood and urine in a dose
      dependent fashion, and in sputum. CONCLUSION: Patients were safely injected
      intratumorally with Ad-p53. Objective antitumor activity was detected in several
      patients. The infectious Ad-p53 in body fluids was asymptomatic, and suggests
      that systemic or regional treatment may be tolerable. These results suggest the
      further investigation of Ad-p53 as a therapeutic agent for patients with HNSCC.

PMID- 9626225
TI  - Randomized phase II study of two schedules of topotecan in previously treated
      patients with ovarian cancer: a National Cancer Institute of Canada Clinical
      Trials Group study.
AB  - PURPOSE: As topotecan is S-phase-specific, its efficacy is likely schedule
      dependent. Therefore, a randomized study using a "pick the winner" design was
      undertaken to compare two schedules in patients with recurrent ovarian cancer.
      PATIENTS AND METHODS: Patients with recurrent epithelial ovarian cancer
      previously treated with no more than two separate regimens of chemotherapy, one
      of which had to be platinum-containing, were randomized to either topotecan 1.5
      mg/m2 intravenously (i.v.) over 30 minutes daily for 5 days repeated every 21
      days (arm A, the standard arm), or topotecan 1.75 mg/m2 as a 24-hour infusion
      once a week for 4 weeks repeated every 6 weeks (arm B, the experimental arm).
      RESULTS: Sixty-six patients were eligible and 63 were assessable for response.
      The response rate in arm A was 22.6% (95% confidence interval [CI], 9.6% to
      41.2%), which was significantly superior to that in arm B, 3.1% (95% CI, 0.1% to
      16%) (P = .026). The regimens were not equitoxic, with 94% of patients on arm A
      experiencing grade 3 or 4 granulocytopenia as opposed to 52% on arm B.
      CONCLUSION: The weekly 24 hour infusion of topotecan at 1.75 mg/m2 was
      ineffective in relapsed ovarian cancer. The daily-times-five schedule remains the
      schedule of choice. As the regimens were not equitoxic, one cannot differentiate
      between an ineffective schedule and an ineffective dose as the reason for the
      differing response rates. However, the degree of myelotoxicity that already
      occurs will preclude any substantially higher dosing with the weekly regimen.

PMID- 9626226
TI  - Telomerase activity as a biomarker for (pre)neoplastic cervical disease in
      scrapings and frozen sections from patients with abnormal cervical smear.
AB  - PURPOSE: To evaluate the diagnostic value of semi-quantitative telomerase
      activity assessment in cervical scrapings together with human papillomavirus
      (HPV) typing for detection of (pre)neoplastic cervical lesions and to compare
      telomerase activity in cervical scrapings and frozen specimens from the same
      patients. PATIENTS AND METHODS: A cross-sectional study was performed in 161
      patients referred for an abnormal cervical cytology report. In cervical
      scrapings, telomerase activity was determined by modified telomere repeat
      amplification protocol (TRAP) assay and HPV typing by polymerase chain reaction
      (PCR) with general and type-specific primers. Final diagnosis was made by
      pathologic examination of biopsy and/or loop excision specimens. RESULTS:
      Telomerase activity was detectable in assessable scrapings from one of nine (11%)
      patients without cervical intraepitheleal neoplasia (CIN), in three of 26 (12%)
      with CIN I, eight of 35 (22%) with CIN II, 18 of 62 (29%) with CIN III, and four
      of 13 (31%) with cancer. Sensitivity and negative predictive value of the TRAP
      assay for CIN II/III and cancer lesions were 25% and 28%, respectively, while
      specificity for no CIN or CIN I was 89%. In representative frozen sections,
      frequency of detectable telomerase activity was related to grade of CIN/cancer;
      none of 21 normal cervices, none of two CIN I, two of 12 (17%) CIN II, 10 of 31
      (32%) CIN III, and 18 of 21 (86%) cervical cancer lesions were telomerase
      positive (P < .0005). Telomerase activity levels in paired scrapings and frozen
      sections appeared to be only weakly related; telomerase-positive sections with
      negative scrapings and vice versa (only in CIN III) were observed. In oncogenic
      HPV-negative scrapings (n = 14), no telomerase activity was detected, but in
      frozen sections, telomerase activity levels appeared to be unrelated to presence
      of specific HPV types. CONCLUSION: Telomerase activity is more frequent in higher
      grade CIN/cervical cancer lesions. Telomerase activity assessment in cervical
      scrapings has a low sensitivity for CIN II/III and/or cervical cancer and does
      not appear to be useful in primary screening for cervical cancer. However,
      increased telomerase activity in frozen CIN sections may be a possible marker of
      progressive disease.

PMID- 9626227
TI  - Treatment of intrahepatic cancers with radiation doses based on a normal tissue
      complication probability model.
AB  - PURPOSE: To attempt to safely escalate the dose of radiation for patients with
      intrahepatic cancer, we designed a protocol in which each patient received the
      maximum possible dose while being subjected to a 10% risk of radiation-induced
      liver disease (RILD, or radiation hepatitis) based on a normal tissue
      complication probability (NTCP) model. We had two hypotheses: H1; with this
      approach, we could safely deliver higher doses of radiation than we would have
      prescribed based on our previous protocol, and H2; the model would predict the
      observed complication probability (10%). PATIENTS AND METHODS: Patients with
      either primary hepatobiliary cancer or colorectal cancer metastatic to the liver
      and normal liver function were eligible. We used an NTCP model with parameters
      calculated from our previous patient data to prescribe a dose that subjected each
      patient to a 10% complication risk within the model. Treatment was delivered with
      concurrent hepatic arterial fluorodeoxyuridine (HA FUdR). Patients were evaluated
      for RILD 2 and 4 months after the completion of treatment. RESULTS: Twenty-one
      patients completed treatment and were followed up for at least 3 months. The mean
      dose delivered by the current protocol was 56.6 +/- 2.31 Gy (range, 40.5 to 81
      Gy). This dose was significantly greater than the dose that would have been
      prescribed by the previous protocol (46.0 +/- 1.65 Gy; range, 33 to 66 Gy; P <
      .01). These data are consistent with H1. One of 21 patients developed RILD. The
      complication rate of 4.8% (95% confidence interval, 0% to 23.8%) did not differ
      significantly from the predicted 8.8% NTCP (based on dose delivered) and excluded
      a 25% true incidence rate (P < .05). This finding supports H2. CONCLUSION: Our
      results suggest that an NTCP model can be used prospectively to safely deliver
      far greater doses of radiation for patients with intrahepatic cancer than with
      previous approaches. Although the observed complication probability is within the
      confidence intervals of our model, it is possible that this model overestimates
      the risk of complication and that further dose escalation will be possible.
      Additional follow-up and accrual will be required to determine if these higher
      doses produce further improvements in response and survival.

PMID- 9626228
TI  - Patterns of recurrence following a negative sentinel lymph node biopsy in 243
      patients with stage I or II melanoma.
AB  - PURPOSE: To determine the patterns of recurrence and causes of regional nodal
      basin failure in stage I or II melanoma patients who had a histologically
      negative sentinel lymph node (SLN) and whose regional nodal basins were not
      dissected following lymphatic mapping and SLN biopsy. PATIENTS AND METHODS: The
      records of 344 patients with primary cutaneous melanoma who underwent lymphatic
      mapping and SLN biopsy between 1991 and 1995 at The University of Texas M.D.
      Anderson Cancer Center were reviewed. Of 322 patients who underwent successful
      lymphatic mapping procedures, 270 had histologically negative SLNs; mapped nodal
      basins were observed without further surgical intervention in 243 of these 270
      patients. Recurrence patterns were analyzed from this cohort and a histologic
      reevaluation of all previously identified SLNs on which a biopsy had been taken
      was performed in patients who developed recurrent disease. RESULTS: Of 243
      patients with a histologically negative SLN, 27 (11%) developed local, in
      transit, regional nodal, and/or distant metastases after a median follow-up time
      of 35 months. Ten patients (4.1%) developed a nodal recurrence in the previously
      mapped basin, either solely or as a component of the first site of recurrence.
      Detailed analysis of the SLNs in these 10 patients demonstrated evidence of
      occult metastases in 80% by serial sectioning or immunohistochemical staining.
      CONCLUSION: Regional nodal failures in melanoma patients following a negative SLN
      biopsy are infrequent and to date have most commonly occurred because
      conventional histologic evaluation was unable to identify occult metastatic
      disease. These data provide further evidence that lymphatic mapping and SLN
      biopsy accurately reflect the status of the regional nodal basin. Specialized
      pathologic techniques are necessary to reduce further the already low false
      negative rates and to improve disease staging.

PMID- 9626229
TI  - Resection of metastatic renal cell carcinoma.
AB  - PURPOSE: Resection of solitary metastases from renal cell carcinoma (RCC) is
      associated with a 5-year survival rate of 35% to 50%. Selection criteria are not
      well defined. PATIENTS AND METHODS: We retrospectively analyzed our experience
      with 278 patients with recurrent RCC from 1980 to 1993. RESULTS: One hundred
      forty-one of 278 patients underwent a curative metastectomy for their first
      recurrence (44% 5-year overall survival [OS] rate), 70 patients underwent
      noncurative surgery (14% 5-year OS rate), and 67 patients were treated
      nonsurgically (11% 5-year OS rate). Favorable features for survival were a
      disease-free interval (DFI) greater than 12 months versus 12 months or less (55%
      v 9% 5-year OS rate; P < .0001), solitary versus multiple sites of metastases
      (54% v 29% 5-year OS rate; P < .001), and age younger than 60 years (49% v 35% 5
      year OS rate; P < .05). Among 94 patients with a solitary metastasis, lung (n =
      50; 54% 5-year OS rate) was more favorable than brain (n = 11; 18% 5-year OS
      rate; P < .05). Survival rates after curative resection of second and third
      metastases were not different compared with initial metastectomy (46% and 44%,
      respectively, v 43% 5-year OS rates; P = nonsignificant). Favorable predictors of
      survival by multivariate analysis included a single site of first recurrence,
      curative resection of first metastasis, a long DFI, a solitary site of first
      metastasis, and a metachronous presentation with recurrence. CONCLUSION: Selected
      patients with recurrent RCC who can undergo a curative resection of their disease
      have a good opportunity for long-term survival, particularly those with a single
      site of recurrence and/or a long DFI.

PMID- 9626230
TI  - Prostate-specific antigen doubling times are similar in patients with recurrence
      after radical prostatectomy or radiotherapy: a novel analysis.
AB  - PURPOSE: Some investigators have analyzed the rate of growth of prostate cancer
      that has recurred after definitive radiotherapy or radical prostatectomy using
      serum prostate-specific antigen (PSA) doubling times (DT). We examined all PSA
      values in recurrent patients to determine the pattern and rate of increase in PSA
      after radiation therapy and radical prostatectomy. PATIENTS AND METHODS: Charts
      of 96 recurrent radical prostatectomy patients (mean age, 62.8 years; range, 47
      to 76) and 42 recurrent radiation therapy patients (mean age, 67.2 years; range,
      52 to 83) were reviewed. All available PSA values between the date of
      operation/radiation treatment and last follow-up evaluation or the initiation of
      second-line therapy are included. Rate of PSA DT was not assumed to be constant
      over time; it was instead allowed to vary. We use a piecewise linear random
      coefficients model in time for log (PSA), which allowed different mean models for
      both treatments. RESULTS: The PSA DT in the first year after radiation therapy
      was--1.17 years, which reflects the continuous decline in PSA in the average
      patients during the first year after radiotherapy despite eventual biochemical
      progression. In contrast, the PSA DT in the radical prostatectomy group was 0.66
      in the first year. In year 2, after radiation therapy, the PSA DT was lengthy at
      1.82 years, significantly longer (P = .0025) than in the radical prostatectomy
      group (0.76 years). After year 2, there were no significant differences between
      the two groups (P > .05). CONCLUSION: A piecewise linear random-coefficients
      model enables interval analysis of PSA DT. While the PSA DT after radiation
      therapy and radical prostatectomy are different in the first 2 years, the rate of
      increase in PSA appears to be similar in the two groups after year 2, which
      suggests the rate of growth of cancers that recur after radiation therapy and
      radical prostatectomy is similar.

PMID- 9626231
TI  - Economic evaluation of chemotherapy with mitoxantrone plus prednisone for
      symptomatic hormone-resistant prostate cancer: based on a Canadian randomized
      trial with palliative end points.
AB  - PURPOSE: To evaluate the economic consequences of the use of chemotherapy in
      patients with symptomatic hormone-resistant prostate cancer (HRPC) in the context
      of a previously published Canadian open-label, phase III, randomized trial with
      palliative end points. PATIENTS AND METHODS: The trial randomized 161 patients to
      initial treatment with mitoxantrone and prednisone (M + P) or to prednisone alone
      (P) and showed better palliation with M + P. There was no significant difference
      in survival. A detailed retrospective chart review was performed of resources
      used from randomization until death of 114 of 161 patients enrolled at the three
      largest centers: these included hospital admissions, outpatient visits,
      investigations, therapies (which included all chemotherapy and radiation), and
      palliative care. Cancer center and community hospital costs were calculated by
      using the hotel approximation method and case costing from the Ontario Case Cost
      Project, respectively. Cost-utility analysis was performed by transforming the
      European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 global
      quality-of-life item measured every 3 weeks on trial to an estimate of utility,
      and extending the last known value through to death or last follow-up. RESULTS:
      The mean total cost until death or last follow-up by intention-to-treat was M + P
      CDN $27,300; P CDN $29,000. The 95% confidence intervals on the observed cost
      difference ranged from a saving of $9,200 for M + P (with palliative benefit) to
      an increased cost of $5,800 for M + P. The major proportion of cost (M + P 53% v
      P 66%; CDN $14,500 v $19,100) was for inpatient care. Initial M + P was
      consistently less expensive in whichever time period was used to compare costs.
      Cost-utility analysis showed M + P to be the preferred strategy with an upper 95%
      confidence interval for the incremental cost-utility ratio of CDN $19,700 per
      quality-adjusted life-year (QALY). CONCLUSION: A treatment that reduces symptoms
      and improves quality of life has the potential to reduce costs in other areas.
      Economic factors should not influence the clinical decision as to whether to use
      M + P in a symptomatic patient.

PMID- 9626232
TI  - Breast cancer metastatic to the choroid.

PMID- 9626233
TI  - Sharing information with patients.

PMID- 9626234
TI  - Are ABVD and MOPP/ABV truly equivalent for treating Hodgkin's disease at advanced
      stages?

PMID- 9626235
TI  - Oral versus intravenous methotrexate: another opinion.

PMID- 9626236
TI  - Radiation-induced breast cancer after treatment for Hodgkin's disease.

PMID- 9626237
TI  - Late solid tumors after treatment for Hodgkin's disease.

PMID- 9626238
TI  - Radiotherapy error analysis older than yesterday.

PMID- 9626239
TI  - Paclitaxel for the treatment of lymphoma.

PMID- 9626240
TI  - Monitoring methotrexate levels in osteosarcoma.

PMID- 9626241
TI  - Refractory definitions of tumor response.

PMID- 9626242
TI  - Suicide among cancer patients.

PMID- 9626243
TI  - Longitudinal study of the contractile and electrical properties of single human
      thenar motor units.
AB  - Serial motor unit number estimates have shed important light on the extent and
      rates of motoneuron losses in aging and amyotrophic lateral sclerosis. However,
      the estimates alone provide few clues to the health and functional status of
      surviving motor units. A reliable means for assessing the functional status of
      the surviving motor units would therefore by a welcome addition to our present
      tools for studying motor units. Examining the physiological properties of samples
      of motor units drawn at intervals during the course of a motoneuronal disease
      suffers from the important limitation that the samples may not be representative
      of one another. The latter problem could be circumvented by serially studying the
      same motor units. This study describes a noninvasive technique capable of
      longitudinally tracking the contractile and electrical properties of specific
      single thenar motor units in healthy subjects, in some instances over several
      years. The technique proved to be reasonably reliable and provided information on
      a wide range of contractile and electrical properties of motor units. Such an
      approach could serve as a potentially powerful and sensitive means of studying
      the life histories of single motor units in aging, diseases of the motoneuron,
      and in the latter instances, the responses of the motoneurons to treatment.

PMID- 9626244
TI  - Paraneoplastic demyelinating neuropathy, subacute sensory neuropathy, and anti-Hu
      antibodies: clinicopathological study of an autopsy case.
AB  - A patient with anti-Hu antibodies, small-cell lung carcinoma, and autopsy-proven
      subacute sensory neuropathy had early slowing of motor and sensory conduction
      velocities. In the peripheral nerves, chronic demyelinating and remyelinating
      lesions with axonal degeneration were associated with an inflammatory reaction
      consisting of CD8+ T cells and CD68+ macrophages. On immunohistochemical testing,
      the patient's serum did not react with normal nerve, suggesting that the Hu
      proteins were not the target of the inflammatory reaction in the nerve.

PMID- 9626245
TI  - Different indentation velocities activate different populations of
      mechanoreceptors in humans.
AB  - We have examined whether different skin machanoreceptors are activated by
      different indentation velocities of a tactile probe. Indentations of 300 microns
      at velocities of 100 and 400 microns/ms were applied at the dorsolateral side of
      the foot and at the tip of digit III. Compound sensory action potentials (CSAPs)
      were recorded from the sural and median nerves, respectively. The amplitudes of
      the tactile CSAPs were < 1-2 muV, and less than 15% of the CSAPs evoked by
      electrical stimulation. The areas of the polyphasic tactile CSAPs were 35-38%
      smaller at 100 microns/ms than at 400 microns/ms. The maximal sensory nerve
      conduction velocities (SNCVs) were higher in the median than in the sural nerves.
      In both nerves, the SNCVs were similar at electrical and 400-micron/ms tactile
      stimulation but 11-17% lower at 100-micron/ms stimulation. Cocaine hydrochloride
      was applied iontophoretically at the dorsolateral side of the foot, causing a
      decrease of 50% of the CSAP evoked by 100 microns/ms but only 14% at 400
      microns/ms. These studies suggested that identation at 400 microns/ms activated
      mainly deeply placed (Pacini corpuscles) and to some extent superficial
      mechanoreceptors, whereas the 100-micron/ms indentation activated primarily
      superficially situated receptors (Meissner corpuscles, and some slowly adapting
      units).

PMID- 9626246
TI  - Clinical and pathological correlations in Charcot-Marie-Tooth neuropathy type 1A
      with the 17p11.2p12 duplication: a cross-sectional morphometric and
      immunohistochemical study in twenty cases.
AB  - In a cross-sectional, clinical, and morphometric analysis we assessed the
      correlation between the clinical and pathological evolution of disease in 20
      unrelated patients of various ages affected by Charcot-Marie-Tooth neuropathy
      type 1A (CMT1A) with the 17p11.2p12 (peripheral myelin protein 22, PMP22)
      duplication. The severity of neurologic deficits and slowing of motor conduction
      velocity at the median nerve did not vary significantly with the patients' age.
      The amount of demyelination was significantly higher below 15 years than in older
      age groups; in contrast, myelinated fiber and onion bulb densities were similar
      at all ages. The results indicate that in duplicated CMT1A, the pathological
      process develops early in life and progresses little during the course of the
      disease. Younger patients had lower g-ratio values, suggesting that the trigger
      of demyelination in early years could be a hypermyelination, resulting from PMP22
      overexpression. Yet none of the 20 patients examined had immunohistochemical
      evidence of altered PMP22 expression. The early onset and development of the
      disorder make it difficult to detect PMP22 overdosage in nerve biopsies.

PMID- 9626247
TI  - Motor unit size estimation of enlarged motor units with surface electromyography.
AB  - Surface EMG is hardly used to estimate motor unit (MU) characteristics, while its
      non-invasiveness is less stressful for patients and allows multi-electrode
      recordings to investigate different sites of the muscle and MU. The present study
      compares motor unit potentials (MUPs) obtained with surface EMG and macro EMG
      during voluntary contraction of the biceps brachii muscle of patients with
      enlarged MUs caused by prior poliomyelitis. Averaged surface MUPs were obtained
      by means of needle EMG (SMUP1) and surface EMG (SMUP2) triggering. The MUPs area
      and peak amplitudes correlated well when comparing the macro MUP and SMUP1 of the
      same MUs. When MU populations of different patients were compared, the SMUP1s and
      SMUP2s were equally sensitive to pathology as macro MUPs. In this, the late non
      propagating positive wave (only present in unipolar recordings) is more robust
      than the triphasic propagating wave. Therefore, surface EMG can be used for
      detecting enlarged MUs.

PMID- 9626248
TI  - Age-related remodeling of neuromuscular junctions on type-identified diaphragm
      fibers.
AB  - Previous studies have reported fiber-type differences in the morphological
      adaptations of neuromuscular junctions (NMJs) to aging by comparing limb muscles
      consisting of predominantly type I or II fibers. A confounding factor in these
      studies is age-related change in activity, which may differ between muscles. In
      the present study, we assessed age-related changes of the NMJ in type-identified
      fibers of the rat diaphragm muscle, which maintains consistent inspiratory
      related activation throughout life. In 6- and 24-month-old rats, a fluorescent
      triple-labeling technique was used to visualize phrenic axons, presynaptic nerve
      terminals, and postsynaptic acetylcholine receptors (end-plates) on type
      identified fibers. The NMJs were then imaged using three-dimensional (3D)
      confocal microscopy. On type IIx and IIb fibers, nerve terminal and end-plate 2D
      planar and 3D surface areas expanded, and the number of nerve terminal and end
      plate branches increased, indicating fragmentation of the NMJ with aging. On the
      other hand, NMJs on type I and IIa fibers displayed little adaptation. These
      morphological adaptations may be geared toward maintaining the efficacy of
      inspiratory-related activity of the diaphragm muscle, but may affect the
      functional reserve of the aging diaphragm.

PMID- 9626249
TI  - Mononeuropathies associated with liver transplantation.
AB  - Mononeuropathies associated with orthotopic liver transplantation were evaluated
      in a prospective manner. Ten percent of liver transplant recipients were noted to
      have focal peripheral nerve lesions in the postoperative period. The ulnar nerve
      was most commonly involved, with intraoperative compression or postoperative
      trauma as possible mechanisms of injury. Other upper extremity mononeuropathies
      were likely a result of vascular cannulations. No brachial plexus injuries
      occurred. Diabetes and alcoholism were not risk factors for the development of a
      mononeuropathy.

PMID- 9626251
TI  - Normal needle electromyographic insertional activity morphology: a clinical and
      simulation study.
AB  - Needle electromyographic insertional activity waveform morphology, and mechanisms
      of generation, have received little attention. This study analyzes the individual
      component waveforms that contribute to the burst of electrical activity known as
      insertional activity. One hundred monopolar needle insertions were slowly
      performed and high speed recorded to allow better separation of the contributing
      individual component waveforms. Analysis of the many waveforms recorded
      demonstrates several classes of potentials. All of these could be reconstructed
      by the summation of two basic or elementary waveform patterns: a biphasic
      initially negative spike with or without a "prepotential" similar to an end-plate
      spike, and the biphasic initially positive spike with a slowly declining negative
      phase, similar to a positive sharp wave, though shorter in duration. The
      relationship between these elementary waveforms and their hypothesized generator
      sources is discussed.

PMID- 9626250
TI  - Differences in both inositol 1,4,5-trisphosphate mass and inositol 1,4,5
      trisphosphate receptors between normal and dystrophic skeletal muscle cell lines.
AB  - Human normal (RCMH) and Duchenne muscular dystrophy (RCDMD) cell lines, as well
      as newly developed normal and dystrophic murine cell lines, were used for the
      study of both changes in inositol 1,4,5-trisphosphate (IP3) mass and IP3 binding
      to receptors. Basal levels of IP3 were increased two- to threefold in dystrophic
      human and murine cell lines compared to normal cell lines. Potassium
      depolarization induced a time-dependent IP3 rise in normal human cells and cells
      of the myogenic mouse cell line (129CB3), which returned to their basal levels
      after 60 s. However, in the human dystrophic cell line (RCDMD), IP3 levels
      remained high up to 200 s after potassium depolarization. Expression of IP3
      receptors was studied measuring specific binding of 3H-IP3 in the murine cell
      lines (normal 129CB3 and dystrophic mdx XLT 4-2). All the cell lines bind 3H-IP3
      with relatively high affinity (Kd: between 40 and 100 nmol/L). IP3 receptors are
      concentrated in the nuclear fraction, and their density is significantly higher
      in dystrophic cells compared to normal. These findings together with high basal
      levels of IP3 mass suggest a possible role for this system in the deficiency of
      intracellular calcium regulation in Duchenne muscular dystrophy.

PMID- 9626252
TI  - Activity of phasic motor neurons partially transforms the neuronal and muscle
      phenotype to a tonic-like state.
AB  - We present a model preparation, the crayfish, to investigate chronic stimulation
      effects in muscle fiber type and neuronal conversion from fast to slow. The
      results show a presynaptic alteration in transmitter release after 1 week of
      stimulation at 5 Hz for a 2-h daily regime. With the same stimulation paradigm,
      the muscle proteins displayed on a polyacrylamide gel only start to show changes
      after 3 weeks. The original phasic motoneurons within 1 week display an enhanced
      ability to resist synaptic depression, as do tonic motoneurons. The results show
      that identified phasic motoneurons and muscle fibers in the crayfish can be
      transformed to a toniclike state, and that the nerve terminals convert prior to
      the muscle fibers. Electrophysiological clinical measures indicating a change in
      transmitter release properties may not necessarily mean that the muscle fibers
      have fully adapted for long-lasting effects. This preparation allows stimulation
      conditions to be examined with ease.

PMID- 9626253
TI  - X-linked vacuolated myopathy: membrane attack complex deposition on the surface
      membrane of injured muscle fibers is not accompanied by S-protein.
AB  - We have studied the expression of S-protein on the muscle from patients with X
      linked vacuolated myopathy [characterized by the deposition of the complement C5b
      9 membrane attack complex (MAC) over abnormal muscle fibers] and controls by
      immunocytochemistry and immunoblotting. No expression was detected on muscle from
      controls and patients with X-linked vacuolated myopathy. These findings suggest
      that S-protein does not render the MAC inactive in X-linked vacuolated myopathy.
      This situation may be due to the fact that the pathways of MAC activation and the
      expression of S-protein in X-linked vacuolated myopathy are different from the
      ones observed in ischemic and/or necrotic, or immune diseases. These results
      emphasize the role of the membrane complement regulatory proteins (i.e., CD59) in
      X-linked vacuolated myopathy.

PMID- 9626254
TI  - Modulation of vastus medialis motoneuronal excitability by sciatic nerve
      afferents.
AB  - We activated the sciatic nerve afferents by either the discharge of a magnetic
      coil or a needle inserted near the nerve. Both types of stimulation induced
      facilitation of the vastus medialis (VM) H reflex, and of the VM response to
      transcranial magnetic stimulation, at the joint time of arrival of conditioning
      and test volleys, while a subsequent inhibition was induced only in the H reflex.
      We conclude that sciatic nerve afferents induce reciprocal inhibition of VM
      motoneurons presynaptically on the la afferent terminals.

PMID- 9626255
TI  - Abnormalities of cardiac repolarization in multiple sclerosis: relationship with
      a model of allergic encephalomyelitis in rat.
AB  - Ventricular repolarization was investigated for the first time in 48 multiple
      sclerosis (MS) patients using measurement of QTc interval on standard
      electrocardiographic recordings. The repolarization process was prolonged
      significantly in MS compared to control subjects (P = 0.0001). This result was
      confirmed with an animal model of MS, i.e., the experimental allergic
      encephalomyelitis in rat. The contribution of prolonged QT to syncopal attack or
      sudden cardiac death in MS patients need further investigation.

PMID- 9626256
TI  - Paraneoplastic motor neuron disease with type 1 Purkinje cell antibodies.
AB  - Autoimmune serological testing is a useful aid for identifying a paraneoplastic
      basis for sporadic motor neuron disease. A 67-year-old woman with ovarian
      carcinoma presented with progressive weakness. Neurological examination was
      suggestive of motor neuron disease with signs of upper motor neuron disorder.
      Electromyography revealed severe motor neuronopathy of the upper extremities.
      Characteristic type 1 Purkinje cell antibodies (anti-Yo antibody) was detected in
      the serum diluted at 1:61,400.

PMID- 9626257
TI  - An assessment of motor unit discharge patterns in stroke patients using a surface
      electromyographic technique.

PMID- 9626258
TI  - Normal postexercise facilitation and depression of motor evoked potentials in
      postpolio patients.
AB  - We studied the effects of exercise on motor evoked potentials (MEPs) elicited by
      transcranial magnetic stimulation in healthy subjects and postpolio patients.
      Subjects performed repeated sets of isometric exercise until the muscle fatigued.
      In both groups, the mean MEP amplitude immediately after each exercise set was
      approximately twice that of the baseline amplitude, indicating similar
      postexercise facilitation, and after fatigue was approximately half that of the
      baseline amplitude, indicating similar postexercise depression. We conclude that
      the intracortical component of central fatigue is normal in postpolio patients.

PMID- 9626259
TI  - Isolated superior gluteal nerve injury: two case reports.
AB  - Isolated superior gluteal nerve injury has been infrequently described in the
      literature, mainly from injections or hip surgery. Its course through the greater
      sciatic foramen renders it at risk in pelvic or hip trauma. We report 2 cases of
      electromyographically documented isolated superior gluteal nerve injury following
      pelvic trauma. These cases illustrate that weakness in hip abduction following
      pelvic trauma may indicate the presence of a superior gluteal nerve injury,
      warranting further clinical and electrodiagnostic evaluation.

PMID- 9626260
TI  - Electromyography of the diaphragm in neuromuscular disease.
AB  - We compared the diaphragmatic electromyographic (EMG) recordings from 32 patients
      with known neuromuscular disease and respiratory symptoms (23 neuropathies, 9
      myopathies) to recordings from 23 normal subjects. Turns analysis of 219-ms
      sections, or epochs, of the EMG demonstrated a significant overlap between
      diagnostic groups, although some epochs from neuromuscular patients were
      significantly different from normal. Empirical rules were derived to infer
      neuropathic and myopathic involvement of the diaphragmatic EMG.

PMID- 9626261
TI  - Effect of temperature on motor responses in organophosphate intoxication.
AB  - We studied the effect of temperature on median motor responses in a 41-year-old
      man with organophosphate intoxication. At 32 degrees C, a normal amplitude
      compound motor action potential (CMAP) and a smaller spontaneous repetitive
      discharge (SRMAP) were present. With warming to 39 degrees C, the CMAP amplitude
      decreased 20%, while the SRMAP amplitude decreased 33%. With cooling to 14
      degrees C, the CMAP amplitude decreased 9%, while the SRMAP became unobtainable.
      Possible mechanisms for these findings are discussed.

PMID- 9626262
TI  - Electromyogram activity and mean power frequency in exercise-damaged human
      muscle.
AB  - Eight volunteers performed two bouts of 50 voluntary maximal eccentric
      contractions of the knee extensors of one leg 3 weeks apart. During maximal
      voluntary isometric contractions performed at intervals after each bout,
      electromyogram (EMG) mean power frequency declined after bout one (P < 0.01
      Duncan's test), whereas integrated EMG did not change after either bout. These
      results suggest that unaccustomed eccentric contractions produce a temporary
      reduction in mean muscle activation frequency during subsequent maximal isometric
      contractions.

PMID- 9626263
TI  - Focal conduction block in n-hexane polyneuropathy.
AB  - A 19-year-old man with an asymptomatic history of recreational gasoline vapor
      inhalation presented with subacute progressive quadriparesis. For 2 weeks, he had
      intensely inhaled Coleman fuel oil vapor, which contains n-hexane. Nerve
      conduction studies including near-nerve needle stimulation showed focal
      conduction block in the bilateral median and ulnar nerves. Sural nerve biopsy was
      consistent with giant axonal neuropathy. Conduction block as seen in this case
      has not heretofore been described in n-hexane polyneuropathy.

PMID- 9626264
TI  - Influence of stimulus cross talk on results of the twitch-interpolation technique
      at the biceps brachii muscle.

PMID- 9626265
TI  - A case of neonatal tetanus with characteristic neurophysiological findings.

PMID- 9626266
TI  - Axonal polyneuropathy in Ehlers-Danlos syndrome.

PMID- 9626267
TI  - Demyelinating polyneuropathy in a patient with chronic myeloid leukemia.

PMID- 9626268
TI  - Individual differences, variability, and student research.

PMID- 9626269
TI  - Trunk muscle performance in early Parkinson's disease.
AB  - BACKGROUND AND PURPOSE: Altered trunk function has been observed in people with
      Parkinson's disease (PD). SUBJECTS: This study investigated the trunk function of
      people with PD, as compared with people without PD. METHODS: Range of motion
      (against 1 N.m of resistance), isometric torque, and isoinertial performance
      against moderate resistance were assessed using an Isostation B-200. RESULTS:
      Group effects between the subjects with PD and the subjects without PD were found
      for all variables. Range of motion into extension and maximum and average
      isometric torque in the directions of extension and right rotation showed group
      effects between subjects classified as being in Hoehn and Yahr stage I and
      subjects classified as being in Hoehn and Yahr stage II. CONCLUSION AND
      DISCUSSION: People with PD exhibit less axial range of motion and isometric and
      isoinertial ability compared with persons without PD. There is a loss of the
      ability to extend the trunk early in the disease. These findings suggest the
      importance of further investigation into the role of strengthening programs soon
      after a diagnosis of PD in order to potentially delay changes in trunk function
      and subsequent functional difficulties.

PMID- 9626270
TI  - Performance on clinical tests of balance in Parkinson's disease.
AB  - BACKGROUND AND PURPOSE: Due to the high incidence of falls in people with
      idiopathic Parkinson's disease (PD), the assessment of standing balance is a key
      component of physical therapist evaluation. This study investigated performance
      on clinical tests of standing balance in subjects with and without PD. SUBJECTS:
      The subjects were 10 persons with PD who had a history of falls (age range = 60
      80 years), 10 persons with PD who had no history of falls (age range = 63-79
      years), and 10 persons with no known neurological impairment (age range = 60-78
      years) who served as a comparison group. METHODS: Subjects were tested on their
      ability to maintain stability in 3 conditions: (1) steady standing (feet apart,
      feet together, tandem stance, step stance, and single-limb stance), (2) in
      response to perturbations generated by self-initiated movements (arm raise,
      functional reach, bend-reach, and step tests), and (3) in response to an external
      perturbation to upright stance (shoulder tug). Balance was measured at peak
      dosage in the levodopa medication cycle (in the morning) and 7 days later.
      RESULTS: The mean Hoehn and Yahr Disability Scale score was 3.0 for the fallers
      with PD and 2.5 for the nonfallers with PD. Performance on the tandem stance,
      single-limb stance, functional reach, and shoulder tug tests demonstrated
      differences between the subjects with PD and the comparison group and between the
      fallers and nonfallers with PD. The results of these tests were highly repeatable
      over 7 days (ICC = .61-.94). CONCLUSION AND DISCUSSION: Although there was a
      small sample size, performance was highly consistent across 7 days when testing
      occurred during peak dosage of levodopa. A small battery of tests were sensitive
      enough to discriminate between people with PD who fall and those with no history
      of falls.

PMID- 9626271
TI  - Movement diagram and "end-feel" reliability when measuring passive lateral
      rotation of the shoulder in patients with shoulder pathology.
AB  - BACKGROUND AND PURPOSE: Findings related to joint function can be recorded with
      movement diagrams or by characterizing the "end-feel" according to the procedure
      described by Cyriax. Because both methods are used to classify pain and
      resistance in relation to joint range of motion (ROM), the purpose of this study
      was to simultaneously evaluate the reliability of these categorizations in a
      patient sample. SUBJECTS: Two physical therapists performed 2 assessments of
      passive lateral rotation of the shoulder in 34 patients. METHODS: Pain and
      resistance findings were recorded using movement diagrams and end-feel
      categories. Intraclass correlation coefficients (ICC[2,1]) were used to analyze
      the ratio (movement diagram) data, and kappa statistics (kappa) were used to
      analyze the categorical (end-feel) data. RESULTS: Intrarater ICCs varied from .58
      to .89. Interrater ICCs for locating maximum pain and resistance in joint ROM
      varied from .85 to .91. Other interrater ICCs were lower (ICC = .34-.88).
      Intrarater kappa values for end-feel were moderate (kappa = .48-.59), and
      interrater kappa values were substantial (kappa = .62-.76). CONCLUSION AND
      DISCUSSION: Movement diagram measures conceptually related to the end of joint
      ROM and end-feel were highly reliable. This finding and the fact that additional
      end-feel categories were introduced in the study may partially explain the end
      feel reliability findings. Consideration of their use in future studies may help
      to determine their clinical utility.

PMID- 9626273
TI  - A new approach to measuring recovery in injured workers with acute low back pain:
      Resumption of Activities of Daily Living Scale.
AB  - BACKGROUND AND PURPOSE: Spontaneous recovery, job satisfaction, and multiple
      other factors make return to work a highly problematic indicator. Available
      client questionnaires fail to consider what was "normal" or "usual" prior to low
      back injury. Based on themes described by injured persons, we suggest a new
      approach to determining "recovery"--the Resumption of Activities of Daily Living
      (RADL) Scale. SUBJECTS: Injured persons and their therapists from 8 different
      clinics participated in the study. METHODS: Twenty subjects completed the RADL
      twice, about 2 days apart, for assessment of test-retest reliability. The RADL
      was administered, along with other questionnaires, to a separate group of 94
      subjects at clinic entry and at discharge or 3 weeks after clinic entry. Both
      subjects and clinicians made baseline predictions concerning return to work and
      global ratings of improvement and ability to return to work at follow-up.
      RESULTS: The RADL showed good psychometric properties (i.e., test-retest
      reliability, internal consistency, responsiveness to change, and discriminative
      abilities). CONCLUSION AND DISCUSSION: The RADL provides a new, standardized
      measure for assessing the extent of recovery from the time of injury to
      initiation of treatment, and concurrent with the course of treatment, using the
      individual's customary level of functioning as the benchmark.

PMID- 9626272
TI  - Determinants of paraspinal muscle cross-sectional area in male monozygotic twins.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to investigate the general
      magnitude and relative contributions of anthropometric, lifestyle, and medical
      history factors and familial aggregation (combined effects of genes and early
      environment) as determinants of paraspinal muscle cross-sectional area (CSA).
      SUBJECTS: The subjects were 65 pair of male monozygotic twins aged 35 to 65 years
      (mean = 49, SD = 8). METHODS: Study methods included magnetic resonance imaging,
      percentage body fat determination, and a detailed interview. RESULTS: Most of the
      anthropometric factors were associated with the CSAs. Familial aggregation was
      the strongest determinant, however, explaining 66% to 73% of the variance in the
      outcomes beyond what age alone predicted. Levels of occupational, sport, and
      leisure-time physical activities reported by the subjects had negligible effects.
      CONCLUSION AND DISCUSSION: The CSAs of the paraspinal muscles were influenced
      more by some combination of genes and early environmental factors than by
      anthropometric factors and lifestyle choices in adulthood.

PMID- 9626274
TI  - Functional Abilities Confidence Scale: a clinical measure for injured workers
      with acute low back pain.
AB  - BACKGROUND AND PURPOSE: The Functional Abilities Confidence Scale (FACS) measures
      self-confidence concerning various movements and postures affected by low back
      pain (LBP). This article describes the scale's development, based on qualitative
      themes suggested by clinicians and patients, and its psychometric properties.
      SUBJECTS: People with work-related LBP injuries and clinicians from 8 different
      rehabilitation clinics participated in the study. METHODS: A group of 20 subjects
      completed the FACS twice, about 2 days apart, for assessment of test-retest
      reliability. The FACS was also administered, together with other measures, to a
      separate group of 94 subjects at clinic entry and at discharge or 3 weeks after
      clinic entry for validity testing. Clinicians rated each subject's physical
      abilities at each point. RESULTS: The FACS showed good psychometric properties
      (i.e., test-retest reliability, internal consistency, responsiveness to change,
      discriminant abilities, and convergent validity). CONCLUSION AND DISCUSSION: The
      FACS is a measure that has potential use in guiding therapists in determining a
      person's initial level of confidence and in monitoring progress during the
      rehabilitation process.

PMID- 9626275
TI  - Personal, interpersonal, and organizational influences on student satisfaction
      with clinical education.
AB  - BACKGROUND AND PURPOSE: Understanding the factors that contribute to student
      satisfaction may lead to improved education in physical therapy. This study
      tested the extent to which variables in the personal, interpersonal, and
      organizational domains influence satisfaction with clinical experiences.
      SUBJECTS: Physical therapist students (N = 113) in 2 phases of their clinical
      experiences at one private school participated. METHODS: A nonexperimental design
      tested 3 models for predicting overall satisfaction. Students completed 3 surveys
      and weekly logs during 8-week-long clinical experiences. RESULTS: The survey
      return rate was 96%. Overall satisfaction with the clinical experience was
      predicted by life satisfaction, gender, off-site events, on-site events,
      interaction between negative events and gender, instructor teaching skills,
      interaction between education phase and gender, variety, and use of selected
      orientation methods. CONCLUSION AND DISCUSSION: Overall satisfaction is predicted
      by variables in all 3 domains. Overall satisfaction was best explained by factors
      in the interpersonal domain and student gender. Causal research is needed to
      confirm whether satisfaction can be improved and whether the results apply to
      other students at other schools. The relationships among satisfaction,
      performance, later job satisfaction, and career commitment need to be explored
      further.

PMID- 9626276
TI  - Cost-effectiveness of preference-based antithrombotic therapy for patients with
      nonvalvular atrial fibrillation.
AB  - BACKGROUND AND PURPOSE: Recent atrial fibrillation guidelines recommend the
      incorporation of patient preferences into the selection of antithrombotic
      therapy. However, no trial has examined how incorporating such preferences would
      affect quality-adjusted survival or medical expenditure. We compared 10-year
      projections of quality-adjusted survival and medical expenditure associated with
      two atrial fibrillation treatment strategies: warfarin-for-all therapy versus
      preference-based therapy. The preference-based strategy prescribed whichever
      antithrombotic therapy, warfarin or aspirin, had the greater projected quality
      adjusted survival. METHODS: We used decision analysis stratified by the number of
      stroke risk factors (history of stroke, transient ischemic attack, hypertension,
      diabetes, or heart disease). The base case focused on compliant 65-year-old
      patients who had nonvalvular atrial fibrillation and no contraindications to
      antithrombotic therapy. RESULTS: In patients whose only risk factor for stroke
      was atrial fibrillation, preference-based therapy improved projected quality
      adjusted survival by 0.05 quality-adjusted life year (QALY) and saved $670. For
      patients who had atrial fibrillation and one additional risk factor for stroke,
      preference-based therapy improved quality-adjusted survival by 0.02 QALY and
      saved $90. In patients who had atrial fibrillation and multiple additional risk
      factors for stroke, preference-based therapy increased medical expenditures and
      did not improve quality-adjusted survival substantially. The benefits of
      preference-flexible therapy arose from the minority of patients who would have
      had a longer quality-adjusted survival if they had been prescribed aspirin rather
      than warfarin. CONCLUSIONS: As do risks of stroke and of hemorrhage, patients'
      preferences help to determine which antithrombotic therapy is optimal. Preference
      based treatment should improve quality-adjusted survival and reduce medical
      expenditure in patients who have nonvalvular atrial fibrillation and not more
      than one additional risk factor for stroke.

PMID- 9626277
TI  - Clinical efficiency tools improve stroke management in a rural southern health
      system.
AB  - BACKGROUND AND PURPOSE: Ischemic stroke is a high-volume and financially draining
      diagnosis at this rural health system. The purpose of this clinical practice
      analysis was to identify resource utilization and clinical process inefficiencies
      and to promote clinically efficient, evidence-based improvements. METHODS: A
      retrospective analysis of medical record and financial databases of 356 patients
      with ischemic stroke was performed. The medical record data were adjusted for
      severity, and outliers were eliminated. The resources utilized by each physician
      were determined. Comparative graphs were prepared, presented, and discussed. The
      physicians implemented two types of changes: (1) alteration of resource
      utilization and consultation patterns and (2) support of clinical process
      improvement. In 1997, a follow-up analysis of 399 patients was performed.
      RESULTS: The initial comparison of internists' to neurologists' patient
      populations found the following: patient age (75 versus 65 years), patient
      severity ratings (2.8 versus 2.5), length of stay (10.7 versus 8.8 days), costs
      ($7360 versus $6862), mortality rates (12.5% versus 8.9%), and aspiration
      pneumonia rate (8.5% versus 3.8%). A comparison of the 1995 analysis to the 1997
      analysis revealed the following per patient resource utilization decreases (all P
      < 0.05): chemistry laboratory, 2.65 to 1.95 studies; intravenous fluids, 2.85 to
      1.85 L; oxygen use, 6.06 to 2.75 U; and nifedipine use, 1.62 to 0.33 capsules.
      The clinical process improvements resulted in the following overall outcomes (all
      P < 0.05 except mortality): length of stay (7.2 days), nonadjusted costs ($6246),
      mortality (6.5%), and rates of pneumonia (2.7%). CONCLUSIONS: Objective analysis
      of resource utilization resulted in physicians changing their individual
      management of stroke and collectively supporting clinical process changes that
      improved clinical and financial outcomes.

PMID- 9626278
TI  - Effect of the Asymptomatic Carotid Atherosclerosis Study on carotid
      endarterectomy in Florida.
AB  - BACKGROUND AND PURPOSE: The value of carotid endarterectomy (CEA) has been
      defined by several recent multicenter trials. The clinical effect of these trials
      remains undetermined since the Asymptomatic Carotid Atherosclerosis Study (ACAS)
      Clinical Advisory (dated September 28, 1994). METHODS: Patients undergoing CEA
      (ICD-9-CM 38.12) in nonfederal Florida hospitals were identified from the
      discharge database. Data were analyzed by federal fiscal year (FY, October 1
      through September 30), comparing the years following the Advisory (FY95-FY96) to
      the preceding 3 years (FY92-FY94). RESULTS: There was a 68.3% increase in the
      number of CEAs during FY95-FY96 (mean FY92-FY94, 7,343; mean FY95-FY96, 12,356).
      This exceeded increases in total hospital discharges (4.5%), surgical discharges
      (2.2%), and the state's population (4.7%). The increase in CEAs spanned all
      patient demographic groups (gender, race, and age), although the magnitude was
      not consistent (range, 57.8% increase for 55 to 64 age group; 92.9% increase for
      > 84 age group). Concomitantly, there was a significant decrease in mortality
      (1.2% versus 0.8%), cardiac complication rate (ICD-9-CM 997.1, 4.1% versus 3.0%)
      and percentage of patients discharged > 7 days postoperatively (8.9% versus
      4.9%). Mean length of stay declined 28% (5.8 versus 4.1 days), and mean adjusted
      charges declined 7% ($19,456 versus $18,055). Although the average case was less
      costly, the increased volume resulted in an estimated $56 million increase in
      annual hospital payments. CONCLUSIONS: The dramatic increase in the number of
      CEAs performed in the state of Florida after release of the ACAS Clinical
      Advisory suggests a causal relationship and mandates further cost-effectiveness
      analyses.

PMID- 9626279
TI  - Diagnosis of stroke by the nonneurologist. A validation study.
AB  - BACKGROUND AND PURPOSE: The first medical contact of an acute stroke victim is
      often a nonneurologist. Validation of stroke diagnosis made by these medical
      doctors is poorly known. The present study seeks to validate the stroke diagnoses
      made by general practitioners (GPs) and hospital emergency service physicians
      (ESPs). METHODS: Validation through direct interview and examination by a
      neurologist was performed for diagnoses of stroke made by GPs in patients under
      their care and doctors working at the emergency departments of 3 hospitals.
      RESULTS: Validation of the GP diagnosis was confirmed in 44 cases (85%); 3
      patients (6%) had transient ischemic attacks and 5 (9%) suffered from
      noncerebrovascular disorders. Validation of the ESP diagnosis was confirmed in
      169 patients (91%); 16 (9%) had a noncerebrovascular diagnosis. Overall, the most
      frequent conditions misdiagnosed as stroke were neurological in nature (cerebral
      tumor, 3; subdural hematoma, 1; seizure, 1; benign paroxysmal postural vertigo,
      1; peripheral facial palsy, 2; psychiatric condition, 6; and other medical
      disorders, 7). CONCLUSIONS: In the majority of cases, nonneurologists (either GPs
      or ESPs) can make a correct diagnosis of acute stroke. Treatment of acute stroke
      with drugs that do not cause serious side effects can be started before
      evaluation by a neurologist and CT scan.

PMID- 9626280
TI  - Neuropsychometric changes in patients after carotid endarterectomy.
AB  - BACKGROUND AND PURPOSE: One hundred twelve patients undergoing elective carotid
      endarterectomy for symptomatic and asymptomatic carotid artery stenosis were
      enrolled in a prospective study to evaluate the incidence of change in
      postoperative cerebral function. METHODS: Patients were evaluated preoperatively
      and postoperatively before hospital discharge and at follow-up 1 and 5 months
      later with a battery of neuropsychometric tests. The results were analyzed by
      both event-rate and group-rate analyses. For event-rate analysis, change was
      defined as either a decline or improvement in postoperative neuropsychometric
      performance by 25% or more compared with a preoperative baseline. RESULTS:
      Approximately 80% of patients showed decline in one or more test scores, and 60%
      had one or more improved test scores at the first follow-up examination. The
      percentage of declined test scores decreased and the percentage of improved test
      scores increased with subsequent follow-up examinations. Group-rate analysis was
      similar for group performance on individual tests. However, a decline in
      performance was seen most commonly on verbal memory tests, and improved
      performance was seen most commonly on executive and motor tests. CONCLUSIONS:
      Neuropsychometric evaluation of patients undergoing carotid endarterectomy for
      significant carotid artery stenosis demonstrates both declines and improvements
      in neuropsychometric performance. The test changes that showed decreased
      performance may be associated with ischemia from global hypoperfusion or embolic
      phenomena, and the improvement seen may be related to increased cerebral blood
      flow from removal of stenosis.

PMID- 9626281
TI  - Carotid atherosclerosis in premenopausal and postmenopausal women and its
      association with risk factors measured after menopause.
AB  - BACKGROUND AND PURPOSE: In women, symptoms of coronary artery disease are delayed
      by 10 to 15 years in comparison with men, most likely because of the protective
      effect of ovarian hormones. This report compares the prevalence and degree of
      carotid atherosclerosis between 292 premenopausal women and 294 women at 5 to 8
      years after menopause. METHODS: Scans were performed in the same laboratory over
      the same time period for both groups. Intima-media thickness (IMT) was averaged
      across the common, bulb, and internal carotids. The plaque index summarized
      degree of focal plaque based on the size and number of plaques throughout both
      carotid systems. RESULTS: Mean IMT was 0.69 mm for premenopausal women and 0.77
      mm for postmenopausal women (P < 0.001). Prevalence of plaque was 25% among
      premenopausal women and 54% among postmenopausal women (P < 0.001). In both
      premenopausal and postmenopausal women, risk factors measured before menopause
      were associated with carotid atherosclerosis. Premenopausal risk factors
      independently associated with IMT were higher pulse pressure (P < 0.001),
      triglycerides (P = 0.002), body mass index (P < 0.001), and study group (a
      surrogate for both age and menopausal status; P < 0.001). Premenopausal risk
      factors independently associated with focal plaque were ever smoking (P = 0.002),
      higher pulse pressure (P = 0.028), higher LDL (P = 0.003), age at baseline (P =
      0.050), and study group (P < 0.001). CONCLUSIONS: Subclinical carotid
      atherosclerosis can be observed in middle-aged women. Risk factors measured
      before menopause are clearly associated with subclinical disease measured both
      concurrently and at 5 to 8 years after menopause.

PMID- 9626282
TI  - A new approach to retrain gait in stroke patients through body weight support and
      treadmill stimulation.
AB  - BACKGROUND AND PURPOSE: A new gait training strategy for patients with stroke
      proposes to support a percentage of the patient's body weight while retraining
      gait on a treadmill. This research project intended to compare the effects of
      gait training with body weight support (BWS) and with no body weight support (no
      BWS) on clinical outcome measures for patients with stroke. METHODS: One hundred
      subjects with stroke were randomized to receive one of two treatments while
      walking on a treadmill: 50 subjects were trained to walk with up to 40% of their
      body weight supported by a BWS system with overhead harness (BWS group), and the
      other 50 subjects were trained to walk bearing full weight on their lower
      extremities (no-BWS group). Treatment outcomes were assessed on the basis of
      functional balance, motor recovery, overground walking speed, and overground
      walking endurance. RESULTS: After a 6-week training period, the BWS group scored
      significantly higher than the no-BWS group for functional balance (P = 0.001),
      motor recovery (P = 0.001), overground walking speed (P = 0.029), and overground
      w alking endurance (P = 0.018). The follow-up evaluation, 3 months after
      training, revealed that the BWS group continues to have significantly higher
      scores for overground walking speed (P = 0.006) and motor recovery (P = 0.039).
      CONCLUSIONS: Retraining gait in patients with stroke while a percentage of their
      body weight was supported resulted in better walking abilities than gait training
      while the patients were bearing their full weight. This novel gait training
      strategy provides a dynamic and integrative approach for the treatment of gait
      dysfunction after stroke.

PMID- 9626283
TI  - Temporal variability of asymptomatic embolization in carotid artery stenosis and
      optimal recording protocols.
AB  - BACKGROUND AND PURPOSE: Although asymptomatic embolization can be detected in
      patients with carotid artery stenosis, its temporal variability is unclear. An
      understanding of this is important in designing optimal recording protocols for
      future prospective studies of the predictive value of embolic signals (ES). We
      determined the effect of repeating and extending recording times in patients with
      symptomatic and asymptomatic carotid stenosis. METHODS: In 20 asymptomatic and 20
      symptomatic subjects with > 60% carotid stenosis, we used transcranial Doppler
      ultrasound to record for ES in the ipsilateral middle cerebral artery. Three 1
      hour recordings were performed on three separate days, and on one occasion (not
      necessarily the first) the recording was extended to 2 hours. The recordings were
      saved onto digital tape for subsequent blinded analysis. RESULTS: Marked temporal
      variability was seen in symptomatic patients in whom the cumulative proportion of
      subjects with ES increased from 10 (50%) after a single hour of recording to 12
      (60%) and 15 (75%) after two and three recordings, respectively. Extending the
      recording to 2 hours increased the yield of ES-positive patients from 6 (30%) to
      8 (40%). In symptomatic patients there was excellent agreement between whether
      patients were positive for ES during each of two consecutive 1-hour recordings
      (kappa = 0.78, P = 0.0003) but poor agreement between the results of two single
      hour recordings performed on different days (kappa = 0.22, P = 0.27). In
      asymptomatic patients, 4 (20%) were ES positive during the first hour; this
      increased to 5 (25%) after the recording was repeated once, with no further
      increase after the third recording. Extending the recording to 2 hours increased
      the yield from 3 (15%) to 7 (35%). In contrast to symptomatic stenoses, in
      patients with asymptomatic stenoses there was fair agreement between whether
      patients were ES positive on two consecutive 1-hour recordings (kappa = 0.49, P =
      0.01) or two single-hour recordings performed on different days (kappa = 0.48, P
      = 0.02). Symptomatic subjects were more likely to have ES (when all 1-hour
      recordings were considered, 24/60 versus 10/60; P = 0.0046). ES in symptomatic
      subjects had a higher relative intensity increase than in asymptomatic subjects
      (P = 0.01). CONCLUSIONS: The temporal variability of ES needs to be taken into
      account in the design of optimal recording protocols and comparisons of results
      from different studies. Extending the duration of recording beyond an hour in
      symptomatic stenoses is of less value, but repeating the recording on a different
      day will often identify additional subjects with ES. In intervention studies in
      symptomatic patients, the time since last symptoms must be considered. In
      asymptomatic stenosis, extending the duration of recording beyond an hour will
      increase the proportion of patients positive for ES.

PMID- 9626284
TI  - A comparison of four methods for distinguishing Doppler signals from gaseous and
      particulate emboli.
AB  - BACKGROUND AND PURPOSE: Many reports in the medical literature have proposed
      methods of differentiating between gaseous and particulate emboli detected with
      the use of transcranial Doppler ultrasound. The purpose of this study was to
      compare the previously published methods with our own sample volume length (SVL)
      parameter to assess the accuracy of each method in classifying emboli. METHODS: A
      pure source of gaseous and particulate emboli was obtained from in vitro and in
      vivo studies, respectively, and recorded onto digital audiotape for off-line
      analysis. In total, 100 gaseous emboli and 215 particulate emboli were analyzed
      to measure four embolic parameters, namely, embolic duration, embolic velocity,
      relative signal intensity increase (measured embolic power [MEP]), and SVL of the
      embolic signal (= Duration x Velocity). Receiver operator characteristic analysis
      was used to assess the optimum threshold for each parameter to differentiate
      between particulate and gaseous emboli, and levels of sensitivity and specificity
      were calculated. RESULTS: Embolic duration and velocity produced the poorest
      levels of sensitivity and specificity compared with the MEP and SVL parameters.
      The optimum thresholds for embolic duration and velocity were 35 ms and 1 m/s,
      respectively, which produced a sensitivity (specificity) of 85.1% (87%) and 87%
      (67%), respectively. The optimum MEP and SVL thresholds were 30 dB and 12.8 mm,
      respectively, which produced a sensitivity (specificity) of 86.5% (95%) and 93%
      (97%), respectively. The SVL and MEP parameters were compared statistically (chi
      2) at chosen specificity values of 90%, 95%, 97%, 99%, and 100%, which showed
      that the SVL sensitivities were statistically greater than MEP sensitivities (P <
      0.01). CONCLUSIONS: SVL is the best parameter for differentiating between gaseous
      and particulate emboli but needs to be calculated with the use of a high-temporal
      resolution spectral analyzer to measure embolic duration and velocity.

PMID- 9626285
TI  - Cerebral microembolism in patients with retinal ischemia.
AB  - BACKGROUND AND PURPOSE: We investigated the frequency of cerebral microembolism
      detected by transcranial Doppler ultrasonography in patients with clinical
      evidence of retinal ischemia, including transient monocular blindness, central
      and branch retinal artery infarction, and ischemic oculopathy, and assessed its
      correlation with carotid artery stenosis. METHODS: Records of 331 consecutive
      patients examined during a 47-month period at the Neurovascular Laboratory were
      reviewed. Of the original 453 intracranial arteries, 186 middle cerebral arteries
      (MCAs) satisfied qualifying criteria that excluded patients with cardiac embolic
      sources. Forty-five MCAs ipsilateral to the symptomatic eye constituted the study
      group. The control group consisted of 141 asymptomatic MCAs. Microembolus
      detection studies were performed on transcranial Doppler instruments equipped
      with special software, and the degree of carotid artery stenosis was measured by
      cerebral or MR angiography or by color duplex studies. RESULTS: Microembolism was
      detected in 40.0% of study MCAs and 9.2% of controls (P < 0.001). In the study
      group, microembolic signals were detected in 61.9% of MCAs tested within a week
      of symptom onset and 20.8% of those tested afterward (P < 0.001). Severe (> or =
      70%) carotid stenosis or occlusion was more frequent in the study group (P <
      0.001). Microembolic signals were detected in 25.3% and 11.2%, respectively, of
      MCAs distal to carotid arteries with 70% to 100% and 0% to 69% stenosis (P =
      0.013). CONCLUSIONS: In patients without cardiac embolic sources, cerebral
      microembolism is frequently present on the side of retinal ischemia, particularly
      during the week after onset of symptoms. It is often associated with severe
      stenosis or occlusion of the ipsilateral carotid artery.

PMID- 9626286
TI  - Early spontaneous improvement and deterioration of ischemic stroke patients. A
      serial study with transcranial Doppler ultrasonography.
AB  - BACKGROUND AND PURPOSE: The purpose of our study was to investigate whether
      emergency transcranial Doppler (TCD) findings and their modifications over the
      first 48 hours are related to early neurological changes in acute ischemic stroke
      patients. METHODS: Ninety-three patients underwent CT scan within 5 hours of a
      first-ever ischemic hemispheric stroke, and TCD serial examinations at 6, 24, and
      48 hours after stroke onset. We classified TCD findings as follows: normal;
      middle cerebral artery (MCA) asymmetry (asymmetry index between affected and
      contralateral MCAs below -21%); and MCA no-flow (absence of flow signal from the
      affected MCA in the presence of ipsilateral anterior and posterior cerebral
      artery signals through the same acoustic window). We considered early
      deterioration and early improvement to be a decrease or an increase of 1 or more
      points, respectively, in the Canadian Neurological Scale score over the same
      period. RESULTS: At 6-hour TCD examination, MCA asymmetry and MCA no-flow were
      present in 6 (22%) and 2 (7%), respectively, of 27 improving patients; in 20
      (43%) and 10 (22%) of 46 stable patients, and in 9 (45%) and 8 (40%) of 20
      deteriorating patients. TCD findings were normal in the remaining patients (P =
      0.001). At serial TCD, we detected early (within 24 hours) recanalization (from
      no-flow to asymmetry or normal and from asymmetry to normal) in 2 (25%) improving
      patients, in 7 (23%) stable patients, and in 5 (29%) deteriorating patients and
      late (between 24 and 48 hours) recanalization in 4 (50%) improving patients, in 6
      (20%) stable patients, and in none of the deteriorating patients (P = 0.03, chi 2
      for trend, improving versus nonimproving irrespective of the timing of
      recanalization). One deteriorating patient (5%) developed a non-flow from an
      initial MCA asymmetry. Logistic regression selected normal TCD (odds ratio [OR],
      0.17; 95% confidence interval [CI], 0.06 to 0.46) as an independent predictor of
      early improvement and abnormal TCD (asymmetry plus no-flow) (OR, 5.02; 95% CI,
      1.31 to 19.3) as an independent predictor of early deterioration. CONCLUSIONS:
      TCD examination within 6 hours after stroke can help to predict both early
      deterioration and early improvement. Serial TCD shows that propagation of
      arterial occlusion is rarely related to early deterioration, whereas the fact
      that it can detect early recanalization (within 24 hours) in deteriorating
      patients and both early and late recanalization (after 24 hours) in improving
      patients suggests the existence of individual time frames for tissue recovery.

PMID- 9626287
TI  - Cerebral blood flow velocity in acute schizophrenic patients. A transcranial
      Doppler ultrasonography study.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to determine whether acutely
      psychotic first-episode schizophrenics show an increased cerebral blood flow
      velocity and whether this condition is reversible on psychopathological
      improvement. METHODS: In the first of two examinations, transcranial Doppler
      ultrasonography and assessment with the Positive and Negative Syndrome Scale
      (PANSS) were performed on 28 acutely psychotic, neuroleptically naive, first
      episode schizophrenics. In the second examination, the same patients were
      assessed psychometrically (PANSS) as well as with Doppler ultrasonography after
      psychopathological improvement. RESULTS: Acutely psychotic first-episode
      schizophrenics showed a significant increase of the mean velocity on both sides
      in the middle and anterior cerebral arteries and in the right posterior cerebral
      artery. Blood flow showed significant correlations with productive psychotic
      symptoms. After psychopathological improvement there was a bilateral
      normalization of the mean velocity in the middle, anterior, and posterior
      cerebral arteries. CONCLUSIONS: Acutely psychotic first-episode schizophrenics
      show a significantly increased bilateral cerebral blood flow velocity, which
      normalizes on psychopathological improvement. There were significant correlations
      of cerebral blood flow velocity with psychopathology.

PMID- 9626288
TI  - Reproducibility of functional transcranial Doppler sonography in determining
      hemispheric language lateralization.
AB  - BACKGROUND AND PURPOSE: Since functional transcranial Doppler ultrasonography
      (fTCD) allows convenient and fully automated quantification of language
      lateralization, it seems ideal for longitudinal studies of perfusion changes
      during deterioration as well as recovery of language functions. However, during
      serial examinations, the technical, stochastic, and physiological variabilities
      of cerebral blood flow velocities (CBFV) have to be considered. Therefore, before
      fTCD is accepted as a tool for evaluation of changes in lateralization in the
      diseased state, its reliability in healthy subjects needs to be determined.
      METHODS: We performed fTCD during a word generation task based on a previously
      validated technique with automated calculation of the averaged CBFV differences
      in the middle cerebral arteries providing an index of lateralization (LI).
      RESULTS: (1) The accuracy of the LI as assessed by the confidence interval was
      better than 1% of the mean hemispheric difference. (2) On repeated examination,
      LIs obtained from 10 subjects showed a high test-retest reproducibility (Pearson
      product moment correlation coefficient r = 0.95, P < 0.0001). (3) On 10 repeated
      assessments of LI in the same subject, no practice effects were detected.
      CONCLUSIONS: Functional TCD is a suitable and very robust tool for the
      longitudinal quantitative measurement of cerebral language lateralization.

PMID- 9626289
TI  - Multivariate analysis of predictors of hematoma enlargement in spontaneous
      intracerebral hemorrhage.
AB  - BACKGROUND AND PURPOSE: We conducted this study to determine, through use of
      multivariate analyses, the independent predictors of hematoma enlargement
      occurring after hospital admission in patients with spontaneous intracerebral
      hemorrhage (i.c.h.). METHODS: We reviewed 627 patients with ICH admitted within
      24 hours of onset. The first CT was performed at admission and the second within
      24 hours of admission, and a blood sample was taken for laboratory examinations.
      Univariate and multivariate analyses were performed to assess the relationships
      between hematoma enlargement and time from onset, consciousness level, CT
      findings, amount of alcohol consumption, systolic blood pressure at and after
      admission, clinical outcome, and hematologic parameters. RESULTS: Eighty-eight
      patients (14.0%) showed enlarged hematomas after admission. Multivariate analyses
      revealed that the following five factors were independently associated with
      hematoma enlargement: the time from onset (odds ratio [OR], 0.26 for a 1-SD
      change; 4.9 hours; P < 0.001); the amount of alcohol consumption (OR, 1.50 for 1
      SD; 46.3 g/d; P = 0.002); the sharp of hematoma (OR, 1.40 for 1 SD; 0.45 round; P
      = 0.006); the presence of consciousness disturbance (OR, 1.38 for 1 SD; 0.50
      coma; P = 0.026); and the level of fibrinogen (OR, 0.74 for 1 SD; 87.1 mg/dL; P =
      0.042). Hematoma enlargement was an independent factor increasing the mortality
      rate in the ICH patients (OR, 1.57; P < 0.001). CONCLUSIONS: A particularly high
      likelihood of hematoma enlargement was observed in patients who (in order of
      importance) were admitted shortly after onset, who were heavy drinkers; who had
      an irregularly shaped hematoma, whose consciousness was disturbed, and who had a
      low level of fibrinogen.

PMID- 9626290
TI  - Feeding artery pressure and venous drainage pattern are primary determinants of
      hemorrhage from cerebral arteriovenous malformations.
AB  - PURPOSE: The purpose of this study was to define the influence of feeding mean
      arterial pressure (FMAP) in conjunction with other morphological or clinical risk
      factors in determining the probability of hemorrhagic presentation in patients
      with cerebral arteriovenous malformations (AVMs). METHODS: Clinical and
      angiographic data from 340 patients with cerebral AVMs from a prospective
      database were reviewed. Patients were identified in whom FMAP was measured during
      superselective angiography. Additional variables analyzed included AVM size,
      location, nidus border, presence of aneurysms, and arterial supply and venous
      drainage patterns. The presence of arterial aneurysms was also correlated with
      site of bleeding on imaging studies. RESULTS: By univariate analysis, exclusively
      deep venous drainage, periventricular venous drainage, posterior fossa location,
      and FMAP predicted hemorrhagic presentation. When we used stepwise multiple
      logistic regression analysis in the cohort that had FMAP measurements (n = 129),
      only exclusively deep venous drainage (odds ratio [OR], 3.7; 95% confidence
      interval [CI], 1.4 to 9.8) and FMAP (OR, 1.4 per 10 mm Hg increase; 95% CI, 1.1
      to 1.8) were independent predictors (P < 0.01) of hemorrhagic presentation; size,
      location, and the presence of aneurysms were not independent predictors. There
      was also no association (P = 0.23) between the presence of arterial aneurysms and
      subarachnoid hemorrhage. CONCLUSIONS: High arterial input pressure (FMAP) and
      venous outflow restriction (exclusively deep venous drainage) were the most
      powerful risk predictors for hemorrhagic AVM presentation. Our findings suggest
      that high intranidal pressure is more important than factors such as size,
      location, and the presence of arterial aneurysms in the pathophysiology of AVM
      hemorrhage.

PMID- 9626291
TI  - Evidence for genetic variance in white matter hyperintensity volume in normal
      elderly male twins.
AB  - BACKGROUND AND PURPOSE: White matter hyperintensities (WMHs), as detected by MRI,
      are common among the elderly and are frequently interpreted as representing a
      subclinical form of ischemic brain damage. We used volumetric MR techniques to
      investigate the contribution of genes and the environment to measures of brain
      morphology in a sample of community dwelling elderly male twins. METHODS: Brain
      MR (1.5 T) scans were obtained from 74 monozygotic (MZ) and 71 dizygotic (DZ),
      white, male, World War II veteran twins born in the United States and age 68 to
      79 when scanned. MR quantification used a previously published semiautomated
      segmentation algorithm to segment brain images into total brain, cerebrospinal
      fluid (CSF), and WMH volumes. Twin pair covariances were computed for each
      measure, and structural equation genetic models were fitted to these data.
      RESULTS: Total cranial, brain parenchyma, CSF, and WMH volumes were highly
      correlated in MZ pairs, and correlations in MZ pairs were significantly greater
      than those in DZ pairs. Structural equation modeling indicated heritabilities of
      91%, 92%, and 73%, respectively, for total cranial, brain parenchyma, and WMH
      volumes. Correction for age and head size reduced the heritability of brain
      parenchyma to 62% (95% confidence interval, 56% to 68%) and the heritability of
      WMH volume to 71% (95% confidence interval, 66% to 76%). Proband concordance
      rates for large amounts of WMH were 61% in MZ pairs and 38% in DZ pairs, compared
      with a prevalence of 15% in the entire sample. CONCLUSIONS: This study is the
      first to quantify the relative contribution of genetic and individual
      environmental influences to measures of brain morphology in the elderly.

PMID- 9626292
TI  - Quantitative assessment of mirror movements after stroke.
AB  - BACKGROUND AND PURPOSE: Mirror movements (MM) are involuntary synchronous
      movements of one limb during voluntary unilateral movements of the opposite limb.
      We measured MM in stroke and control subjects and evaluated whether MM after
      stroke are related to motor function. METHODS: Twenty-three patients and 16
      control subjects were studied. A computerized dynamometer was used during two
      squeezing tasks to measure intended movements from the active hand as well as MM
      from the opposite hand. Motor deficits were measured with the arm motor component
      of the Fugl-Meyer scale. RESULTS: During paretic hand squeezing, MM in the
      unaffected hand were detected in 70% (repetitive squeeze) to 78% (sustained
      squeeze) of stroke patients. For both tasks, this was significantly (P < 0.05)
      greater than the incidence of MM in the paretic hand or in either hand of control
      subjects (17% to 44%), except when compared with the incidence of MM in the
      dominant hand of control subjects (56%; P = 0.17). The incidence of MM in the
      paretic hand was not significantly different from that seen in either hand of
      control subjects. Patients with MM in the unaffected hand had significantly
      greater motor deficit than patients without MM. Patients with MM in the paretic
      hand had significantly better motor function than patients without MM.
      CONCLUSIONS: Simultaneously recording motor performances of both hands provides
      precise information to characterize MM. MM in the unaffected hand and in the
      paretic hand are associated with different degrees of motor deficit after stroke.
      Evaluation of MM may be useful for studying mechanisms of stroke recovery.

PMID- 9626293
TI  - Differences in cellular responses to mitogens in arterial smooth muscle cells
      derived from patients with moyamoya disease.
AB  - BACKGROUND AND PURPOSE: Moyamoya disease is a progressive cerebrovascular
      occlusive disease affecting primarily children. The etiology remains unknown. We
      examined the chemotactic and proliferative activities of inflammatory cell
      products from arterial smooth muscle cells (SMCs) derived from moyamoya patients
      and compared them with those from control subjects. METHODS: We used 12 SMC
      strains from moyamoya patients and eight from control subjects. SMC migration was
      examined in a micro chemotaxis chamber. DNA synthesis was measured by an
      immunoperoxidase technique. RESULTS: Platelet-derived growth factor (PDGF)-BB
      markedly stimulated cell migration and DNA synthesis in control SMCs. PDGF-AA
      stimulated only DNA synthesis in control SMCs. In moyamoya SMCs, PDGF-AA and PDGF
      BB stimulated cell migration but not DNA synthesis. Basic fibroblast growth
      factor had little migratory activity but stimulated DNA synthesis in moyamoya
      SMCs and control SMCs. Conversely, hepatocyte growth factor stimulated cell
      migration but not DNA synthesis in moyamoya SMCs and control SMCs. In contrast,
      interleukin-1 beta (IL-1 beta) significantly stimulated the migration and DNA
      synthesis of control SMCs, while it inhibited moyamoya SMC migration. The levels
      of IL-1 beta-induced nitric oxide production did not differ between moyamoya SMCs
      and control SMCs, suggesting that IL-1 beta inhibits the migration of moyamoya
      SMCs through a nitric oxide-independent pathway. CONCLUSIONS: The differences in
      responses to PDGF and IL-1 in moyamoya SMCs are involved in the mechanism by
      which intimal thickening develops in moyamoya disease.

PMID- 9626294
TI  - High levels of myogenic tone antagonize the dilator response to flow of small
      rabbit cerebral arteries.
AB  - BACKGROUND AND PURPOSE: Pressure and shear stress exerted by flowing blood are
      two mechanical forces that play a major role in the regulation of vascular tone.
      We sought to evaluate the interaction between pressure and flow in isolated
      rabbit cerebral arteries. METHODS: Responses to intraluminal flow of isolated
      pressurized rabbit posterior cerebral arteries were investigated at low, medium,
      and high levels of myogenic tone by setting the luminal pressure at 40, 60, and
      80 mm Hg, respectively. RESULTS: At both low and medium levels of myogenic tone,
      flow induced dilation. The response was significantly larger at 40 than at 60 mm
      Hg. At the high level of myogenic tone, the response to flow consisted of a
      combination of an initial transient dilation followed by sustained constriction.
      Flow-induced dilation but not flow-induced constriction response was endothelium
      dependent. Removal of the endothelium inhibited the dilator response by
      approximately 80%. Flow-induced dilation was inhibited (approximately 40%) by N
      omega-nitro-L-arginine (100 mumol/L) but not by indomethacin (10 mumol/L).
      Endothelium removal not only decreased the amplitude of flow-induced dilation but
      also promoted the appearance of flow-induced constriction at low and medium
      levels of myogenic tone. CONCLUSIONS: The intraluminal pressure and in
      consequence the level of myogenic tone at which flow is applied determine the
      nature of the response of the smooth muscle cells of the blood vessel wall.

PMID- 9626295
TI  - Plasminogen activators potentiate thrombin-induced brain injury.
AB  - BACKGROUND AND PURPOSE: Evidence suggests that cerebral edema following
      intracerebral hemorrhage (i.c.h.) results from a mass effect in combination with
      neurotoxic injury from clot-derived substrates such as thrombin. Thrombolytics
      can compete for thrombin inhibitors endogenous to the brain. This study examines
      the effect of intracerebral infusion of thrombolytics, tissue plasminogen
      activator (tPA), and urokinase (uPA), individually and in combination with
      thrombin. METHODS: Various 100 microL solutions were stereotactically infused
      into the right basal ganglia of adult male rats. Animals were euthanized 24 hours
      later, and brain sections were taken for measurement of water, sodium, and
      potassium content. RESULTS: Regardless of dose, when infused independently tPA (2
      micrograms) and uPA (2000 and 5000 Plough units) failed to produce any
      significant tissue edema compared with vehicle control tissues. However, when
      either thrombolytic was infused concomitantly with thrombin (1 or 5 U), brain
      water, sodium, and potassium content all demonstrated a potentiation of thrombin
      induced brain injury (P < 0.05). In addition, animal deaths were significantly
      greater than expected in animals receiving a combination of tPA (2 micrograms)
      and thrombin (5 U) compared with either drug alone (P < 0.001). CONCLUSIONS: This
      study indicates that brain edema caused by thrombin can be greatly amplified by
      the presence of plasminogen activators, perhaps because the latter compete for
      naturally occurring thrombin inhibitors. In the context of ICH, our results
      suggest that the use of tPA or uPA to lyse clotted blood in brain parenchyma may
      promote edema formation in surrounding tissue.

PMID- 9626297
TI  - Inducible cyclooxygenase expression in canine basilar artery after experimental
      subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: Inducible cyclooxygenase (COX-2) has been found to play a
      pathological role in cerebral insult. We investigated the expression of COX-2 in
      the basilar artery after experimental subarachnoid hemorrhage (SAH). METHODS: In
      a canine "two-hemorrhage" model of SAH, the basilar arteries were obtained on day
      2 after a cisternal injection of autologous blood or on days 4, 6, 7, or 9 after
      the second injection. Basilar arteries also were obtained 12 hours after
      intracisternal injection a cytokine: interleukin (IL)-1 beta (0.03 microgram), IL
      6 (3 micrograms), or IL-8 (10 micrograms). Western blotting with a polyclonal
      anti-COX-2 antibody was performed in these arteries. RESULTS: COX-2 protein was
      not demonstrated in the basilar artery in control animals without SAH. However,
      it was expressed in the basilar artery on days 2, 4, 6, and 7 after blood
      injection but not on day 9. Intracisternal injection of IL-1 beta, IL-6, or IL-8
      also induced COX-2 in the basilar artery. CONCLUSIONS: COX-2 expression was
      detected in basilar arterial tissue in both acute and chronic stages after SAH.
      Elevation of inflammatory cytokines after SAH may be involved in the induction of
      COX-2, which may produce sufficient quantities of eicosanoids to affect
      hemodynamics after SAH.

PMID- 9626296
TI  - Role of inducible nitric oxide synthase and cyclooxygenase-2 in endotoxin-induced
      cerebral hyperemia.
AB  - BACKGROUND AND PURPOSE: Bacterial lipopolysaccharide (LPS), an endotoxin, has
      been reported to induce the expression of inducible isoforms of both nitric oxide
      synthase (iNOS) and cyclooxygenase (COX-2) in various cell types. LPS is also
      known to dilate systemic vasculature, including cerebral vessels. This study
      aimed to determine to what extent LPS induces iNOS and COX-2 expression in the
      brain and whether NO and/or cyclooxygenase metabolites derived from iNOS and/or
      COX-2 contribute to the LPS-induced cerebral hyperemia. METHODS: Regional
      cerebral blood flow (rCBF) was measured by laser-Doppler flowmetry in halothane
      anesthetized, artificially ventilated rats for 4 hours after
      intracerebroventricular administration of LPS. RESULTS: LPS at doses of 0.01
      mg/kg to 1 mg/kg caused dose-dependent, progressive increases in rCBF at 1 to 4
      hours after administration. The increase in rCBF was attenuated by systemic
      administration of the selective iNOS inhibitor aminoguanidine (100 mg/kg IP) or
      the selective COX-2 inhibitor NS-398 (5 mg/kg IP), and it was abolished by
      preventing induction of these isoforms with dexamethasone (4 mg/kg IP). LPS
      significantly increased iNOS and COX-2 mRNA, iNOS protein, and iNOS and
      cyclooxygenase enzyme activity. The increases in iNOS and cyclooxygenase enzyme
      activity were eliminated by aminoguanidine and NS-398, respectively.
      Dexamethasone also prevented the increase in iNOS and cyclooxygenase activity.
      CONCLUSIONS: These results indicate that induction of iNOS and COX-2 expression
      and the increased production of NO and vasodilator prostanoids in the brain
      contribute to the elevation in CBF after intracerebroventricular administration
      of LPS.

PMID- 9626298
TI  - Vascular smooth muscle actin cytoskeleton in cerebral artery forced dilatation.
AB  - BACKGROUND AND PURPOSE: We investigated the role of actin polymerization in
      regulating arterial diameter in response to increasing pressure and modulating
      forced dilatation of cerebral arteries at pressures above the upper limit of
      autoregulation. METHODS: Posterior cerebral arteries (n = 12) were isolated and
      pressurized in a special arteriograph that allowed control of intravascular
      pressure and measurement of lumen diameter. Intact arteries in the absence
      (control) or presence of 3.0 mumol/L cytochalasin B (CB), an inhibitor of actin
      polymerization, were subjected to stepwise increases in pressure from 75 to 200
      mm Hg. Lumen diameter was continuously recorded, as was the pressure at which
      forced dilatation (loss of tone) occurred. After a period of time at 200 mm Hg,
      pressure was returned to 75 mm Hg and the extent of tone recovery was evaluated.
      RESULTS: Arteries with and without CB developed a similar amount of tone during
      equilibration at 75 mm Hg: percent tone = 27 +/- 3% for control versus 29 +/- 4%
      for CB arteries (P > 0.05). However, arteries in the presence of CB could not
      withstand pressure as well and underwent FD at significantly lower pressures: 168
      +/- 5 mm Hg for control versus 142 +/- 5 mm Hg for CB arteries (P < 0.01). The
      amount of tone that arteries regained after FD when pressure was returned to 75
      mm Hg was also less in CB arteries: percent tone = 34 +/- 3% for control versus
      11 +/- 2% for CB arteries (P < 0.01). CONCLUSIONS: Cytoskeletal integrity appears
      important for maintaining cerebral arterial diameter during changing
      intravascular pressure. In addition, the process of actin polymerization may be a
      significant contributor to development of myogenic tone after forced dilatation.

PMID- 9626299
TI  - A reproducible model of circulatory arrest and remote resuscitation in rats for
      NMR investigation.
AB  - BACKGROUND AND PURPOSE: Because noninvasive physiological monitoring of cerebral
      blood flow, metabolic integrity, and brain ion and water homeostasis can now be
      accomplished with new, state-of-the-art MR spectroscopy and imaging techniques,
      it is appropriate to develop controllable and reproducible animal models that
      permit prolonged circulatory arrest and resuscitation in the magnet and also
      allow for studies of long-term survival and outcome. We have developed such a
      model in rats that involves minimal surgical preparations and can achieve
      resuscitation remotely within precisely controlled time. METHODS: Cardiac arrest
      was induced by asphyxiation, the duration of which ranged from 8 to 24 minutes.
      Resuscitation was achieved remotely by a slow, intra-aortic infusion of
      oxygenated blood (withdrawn either from the same rat before asphyxia or from a
      healthy donor rat) along with a resuscitation cocktail containing heparin (50
      U/100 g), sodium bicarbonate (0.1 mEq/100 g), and epinephrine (4 micrograms/100
      g). The body temperature was measured by a tympanic thermocouple probe and was
      controlled either by a heating pad (constant tympanic temperature = 37 degrees C)
      or by warm ambient air (constant air temperature = 37 degrees C). Interleaved
      31P/1H nuclear magnetic resonance (NMR) spectroscopy was used in a selected group
      of rats to measure the cerebral metabolism before and during approximately 20
      minutes of circulatory arrest and after resuscitation. RESULTS: The overall
      success rate of resuscitation, irrespective of the duration of cardiac arrest,
      was 82% (51 of 62). With a programmed infusion pump, the success rate was even
      higher (95%). The survival time for rats subjected to 15 and 19 minutes of
      asphyxia with core temperature tightly controlled was significantly lower than
      that with ambient temperature control (P < 0.001 and P < 0.04, respectively).
      High-quality NMR spectra can be obtained continuously without interference from
      the resuscitation effort. Final histological examinations taken 5 days after
      resuscitation showed typical neuronal damages, similar to those found in other
      global ischemia models. CONCLUSIONS: Because the no-flow time and resuscitation
      time can be precisely controlled, this outcome model is ideally suited for
      studies of ischemic and reperfusion injuries in the brain and possibly in other
      critical organs, permitting continuous assessment of long-term recovery and
      follow-up in the same animals.

PMID- 9626300
TI  - Postischemic application of lipid peroxidation inhibitor U-101033E reduces
      neuronal damage after global cerebral ischemia in rats.
AB  - BACKGROUND AND PURPOSE: The lipid peroxidation inhibitor U-101033E was examined
      for effects on cerebral blood flow (CBF), cortical tissue hemoglobin oxygen
      saturation (HbSo2), and neuronal damage. METHODS: Fifteen minutes of global
      cerebral ischemia was induced by two-vessel occlusion and hypobaric hypotension.
      Wistar rats (n = 25) were randomized to receive vehicle (n = 9) or 40 mg/kg U
      101033E (n = 9) intraperitoneally during 2 hours of reperfusion. A sham group (n
      = 7) had neither ischemia nor therapy. Histology was evaluated 7 days after
      ischemia. RESULTS: During late hyperperfusion (at 17 minutes), vehicle-treated
      animals had a higher (P = 0.044) cortical tissue HbSo2 (72.0 +/- 1.4%) than did U
      101033E-treated animals (65.8 +/- 2.5%). Neuronal counts in the superficial
      cortex layer found after 7 days correlated negatively with rCBF (r = -0.76; P <
      0.001) or cortical tissue HbSo2 (r = -0.56; P = 0.028) assessed during the late
      hyperperfusion phase. U-101033E reduced neuronal damage in hippocampal CA1 from
      64.3 +/- 9.2% to 31.2 +/- 8.4% (P = 0.020), as well as in the superficial
      cortical layer from 53.5 +/- 14.6% to 12.8 +/- 11.7% (P = 0.046). While animals
      in the vehicle group had reduced counts in all four examined cortex layers (P <
      0.05 versus sham group), there was significant cortical neuron loss in the U
      101033E group in only one of four areas. U-101033E had no effect on resting CBF
      or CO2 reactivity. CONCLUSIONS: Postischemic application of U-101033E protects
      hippocampal CA1 and cortical neurons after 15 minutes of global cerebral
      ischemia. The results indicate that free radical-induced lipid peroxidation
      contributes to reperfusion injury, a process that can be inhibited by
      antioxidants such as U-101033E.

PMID- 9626301
TI  - The selective inhibitor of neuronal nitric oxide synthase, 7-nitroindazole,
      reduces the delayed neuronal damage due to forebrain ischemia in rats.
AB  - BACKGROUND AND PURPOSE: The present study was designed to investigate whether
      neuronally derived nitric oxide (NO) plays a toxic role in the cascade of
      cellular events triggered by global cerebral ischemia in rats. METHODS: 7
      Nitroindazole (7-NI) was used as a selective inhibitor of neuronal NO synthase.
      Global ischemia was induced for 20 minutes in anesthetized rats following the
      four-vessel occlusion model. Electroencephalogram and brain and body temperatures
      were continuously monitored. All rats were thermoregulated for the entire
      duration of anesthesia. 7-NI (25 mg/kg) or its vehicle was given
      intraperitoneally just after the carotid clamping and again 1 hour later. Rats
      were randomly divided into four groups: (1) vehicle (n = 7); (2) 7-NI (n = 7);
      (3) L-arginine (300 mg/kg IP) +7-NI (n = 7); and (4) 7-NI associated with warming
      to 37 degrees C for 7 hours after disruption of anesthesia to compensate for the
      decrease in temperature induced by 7-NI (n = 9). Seven days after ischemia,
      hippocampal CA1 damage was evaluated by classic histology. The lesion was scored
      with the use of a point scale, and the surviving neurons were counted. RESULTS:
      Lesion scores were significantly lower and neuron counts higher in the two
      (warmed and unwarmed) groups of rats in which 7-NI was given alone than in
      vehicle- and L-arginine +7-NI-treated rats. CONCLUSIONS: The results indicate
      that 7-NI was neuroprotective in 20-minute global ischemia in rats and that the
      neuroprotective effect of 7-NI was mostly due to the blockade of NO synthesis,
      suggesting that NO released from neurons in ischemic conditions has a deleterious
      influence on hippocampal pyramidal neurons.

PMID- 9626302
TI  - Intra-arterial pro-urokinase in ischemic stroke.

PMID- 9626303
TI  - Clinical trials and financial reimbursement.

PMID- 9626304
TI  - High-dose tirilazad for acute stroke (RANTTAS II). RANTTAS II Investigators.

PMID- 9626305
TI  - Endothelins in acute ischemic stroke.

PMID- 9626306
TI  - Training as a prerequisite for reliable use of NIH Stroke Scale.

PMID- 9626307
TI  - Fighting heart disease and stroke. Recommendations of the AHA Stroke Positioning
      Task Force.

PMID- 9626308
TI  - The American Heart Association Stroke Outcome Classification.

PMID- 9626309
TI  - Ethics in surgical research.

PMID- 9626310
TI  - The life and death of Professor Alexander P. Borodin: surgeon, chemist, and great
      musician.

PMID- 9626311
TI  - Management of continuous anastomosis of pancreatic duct and jejunal mucosa after
      pancreaticoduodenectomy: historical study of 300 patients.
AB  - BACKGROUND: Pancreaticojejunostomy is the most problematic anastomosis in the
      reconstruction after pancreaticoduodenectomy. In the past, much of the morbidity
      and mortality associated with this operation was related to problems with this
      anastomosis. Recent data, however, suggest that the use of duct-to-mucosa sutures
      has led to a marked drop in both morbidity and mortality associated with
      pancreaticojejunostomy. METHODS: Among the 300 patients who underwent
      pancreaticoduodenectomy, including pylorus-preserving pancreaticoduodenectomy, 87
      patients underwent traditional pancreaticojejunostomy by invagination of the end
      of the pancreas into the bowel (group B). Recently three-layer anastomosis was
      created in 213 patients. The outer layer was created between the pancreatic
      capsule and the serosa of jejunum. The middle layer was created between the
      pancreatic parenchyma and the seromuscular wall of jejunum. The inner layer was
      placed between the pancreatic duct and a small opening in the antimesenteric
      border of the jejunal mucosa. Among the 213 patients, the inner anastomosis was
      created with interrupted absorbable sutures (group A1) in 93 patients and
      continuous absorbable sutures (group A2) in 120 patients. RESULTS: The three
      groups were similar with respect to age, gender, and primary disease. In the
      anastomosis, the incidence of leakage in group A2 (4.2%) was significantly less
      than in groups B (17.2%, p < 0.01) and A1 (11.8%, p < 0.05). The operative
      mortality rates were 3.2% in group A1, 1.7% in group A2, and 5.7% in group B.
      CONCLUSIONS: We recommend continuous anastomosis of the pancreatic duct and
      jejunal mucosa as a safe procedure after pancreaticoduodenectomy.

PMID- 9626313
TI  - Twenty-five years of experience in the surgical treatment of perforation of the
      ileum caused by Salmonella typhi at the General Hospital of Mexico City, Mexico.
AB  - BACKGROUND: This work summarizes the experience obtained during 25 years in the
      management of intestinal perforations caused by Salmonella typhi with a directed
      resection and anastomosis at the General Hospital of Mexico City. METHODS: A
      total of 352 cases of perforation of the ileum caused by Salmonella typhi seen
      during the course of 25 years were studied. Patients were divided into two
      groups; group A had 236 patients and group B had 116 patients. All patients
      underwent either conventional resection and anastomosis or primary closure (group
      A) or directed intestinal resection of 10 cm at each side of the perforation on
      the basis of anatomopathologic studies with serial sections (group B). RESULTS:
      Morbidity and mortality for group B were each of 1.72%, significantly lower than
      the 33.47% morbidity and 7.20% mortality in group A. CONCLUSIONS: Primary closure
      should be discouraged, even for a single perforation. Instead directed intestinal
      resection is recommended as elective surgery for all cases of typhoid fever
      complicated with intestinal perforation, resecting 10 cm at each side of the
      distal and proximal perforation.

PMID- 9626312
TI  - First experience and technical aspects of isolated liver perfusion for extensive
      liver metastasis.
AB  - BACKGROUND: New drugs and modalities for locoregional tumor treatment in recent
      years may offer new potential for isolated liver perfusion in patients with
      nonresectable liver tumors. The purpose of this study was to prove the
      feasibility of arterial isolated liver perfusion and to assess the tolerance of
      perfusion with high-dose tumor necrosis factor (TNF). METHODS: Twelve patients
      with extensive liver metastases previously treated unsuccessfully with systemic
      chemotherapy underwent isolated hyperthermic liver perfusion using a heart-lung
      machine. High doses of mitomycin were administered in the first six and a
      combination of TNF and melphalan in the last six patients. RESULTS: No operative
      death occurred and no direct postoperative liver failure was observed in any
      patient. In cases of variations of the arterial hepatic blood supply, the
      perfusion was done through the splenic artery or an angiography catheter.
      Histologic analysis of tumor biopsy specimens obtained on the first postoperative
      day revealed major tumor necrosis in 8 of 12 patients. CONCLUSIONS: Isolated
      arterial perfusion of the liver is a complex surgical procedure that is feasible
      in patients with anatomic variations of the hepatic artery. The remarkable
      histologic response to perfusion in several pretreated patients, especially after
      application of high-dose TNF and melphalan, suggests that this modality is very
      effective in tumor killing.

PMID- 9626314
TI  - Saphenectomy in the presence of chronic venous obstruction.
AB  - BACKGROUND: The results of saphenectomy in patients with morphologic and
      functional obstruction were compared with those in patients without obstruction.
      Excision of secondary saphenous varices associated with deep venous obstruction
      has long been considered contraindicated for fear of compromising its collateral
      contribution. Recent advances in accurate functional assessment of venous
      obstruction make it possible to test this concept. METHODS: Saphenectomy was
      carried out in 51 limbs without morphologic or functional obstruction and 64
      limbs with varying grades of venous obstruction. Significant deep venous
      obstruction on ascending venography was present in the latter group. Functional
      assessment of obstruction was based on the arm/foot venous pressure differential
      technique, outflow fraction measurements, and outflow resistance calculations.
      Valve reconstruction was carried out in conjunction with saphenectomy in 81% of
      cases. RESULTS: Saphenectomy was clinically well tolerated in both groups, and
      there was no difference in outcome as measured by objective tests for
      obstruction; improvement in reflux and calf venous pump function was largely
      similar. Among seven limbs with severe preoperative venous obstruction (grade III
      or IV), five (70%) had significantly improved obstructive grading, presumably as
      a result of elimination of reflux flow. CONCLUSIONS: The traditional admonition
      against removal of secondary varices should be reexamined. Saphenectomy may be
      indicated in postthrombotic syndrome with mixed obstruction/reflux. The procedure
      is clinically well tolerated and without malsequelae. Improvement in reflux
      parameters without significant worsening of objective measures of obstruction is
      documented in this group.

PMID- 9626315
TI  - Long-term results of classic antireflux surgery in 152 patients with Barrett's
      esophagus: clinical, radiologic, endoscopic, manometric, and acid reflux test
      analysis before and late after operation.
AB  - BACKGROUND: The classic surgical procedure for patients with Barrett's esophagus
      (BE) has been either Nissen fundoplication or posterior gastropexy with
      calibration of the cardia. METHODS: The purpose of our study was to determine
      late subjective and objective results of these classic surgical techniques in a
      large number of patients with BE. A total of 152 patients were included in this
      prospective protocol. RESULTS: There was 1 death (0.7%) after operation. The late
      follow-up of 100 months demonstrated a high percentage of failures among patients
      with noncomplicated BE (54%) and an even higher figure in patients with
      complicated BE (64%). In 15 patients low grade dysplasia appeared at 8 years of
      follow-up and an adenocarcinoma in 4 patients. Twenty-four-hour pH monitoring
      demonstrated a decrease in acid reflux into the esophagus, and Bilitec studies
      also demonstrated a decrease of duodenoesophageal reflux, but in all cases with a
      higher value than the normal limit. CONCLUSIONS: Classic antireflux surgery in
      patients with BE results in a high percentage of failures at very late follow-up
      because it cannot completely avoid acid and duodenal reflux into the esophagus.

PMID- 9626316
TI  - Risk factors for restenosis after balloon angioplasty in focal iliac stenosis.
AB  - BACKGROUND: The risk factors for restenosis after angioplasty have not yet been
      established because of the inconsistencies among treated lesions, differences in
      the techniques used, and variable end points. We evaluated the predictive
      variables relating to postangioplasty restenosis. METHODS: One hundred sixty-one
      transluminal balloon angioplasties were studied in 138 consecutive patients with
      focal iliac arterial stenosis (< or = 4 cm) caused by arteriosclerosis between
      January 1981 and December 1995. Restenosis was diagnosed on the basis of
      recurrent symptoms associated with an apparent drop in the ankle-brachial
      pressure index and angiographic visualization of restenosis. RESULTS: Being
      younger than 60 years (risk ratio 2.585) and poor runoff (risk ratio 2.328) were
      found to be important variables predicting restenosis by the Cox regression
      model. The restenosis-free patency rates were significantly better in patients
      older than 60 years of age (p = 0.0242), with good distal runoff (p = 0.0487),
      and without diabetes (p = 0.0111). CONCLUSIONS: Being younger than 60 years of
      age and poor distal runoff are important predictors of restenosis after iliac
      balloon angioplasty.

PMID- 9626317
TI  - Locally recurrent soft tissue sarcoma of the extremities.
AB  - BACKGROUND: The management of locally recurrent extremity soft tissue sarcoma
      remains challenging. This study was undertaken to evaluate the long-term outcome
      after therapy for isolated locally recurrent soft tissue sarcoma (STS) of the
      extremity. METHODS: Between January 1, 1980, and December 31, 1990, 52 patients
      were treated at The University of Texas M. D. Anderson Cancer Center for locally
      recurrent extremity STS. The records of the subset of these patients (n = 36)
      with isolated local recurrence were examined to document clinicopathologic and
      treatment factors and to evaluate outcome using the end points of local
      recurrence-free, recurrence-free, and overall survival. RESULTS: Limb-sparing
      conservative surgery was possible in 24 patients (75%). Twelve (33%) of 36
      patients were treated by surgery alone, 23 patients (64%) were treated with
      combined modality therapy (surgery plus radiation and/or chemotherapy), and 1
      patient had radiotherapy only. Sixteen (44%) of 36 patients had no further
      recurrence of any type at a median follow-up of 58 months (range, 4 to 173
      months). The 5-year actuarial local recurrence-free, recurrence-free, and overall
      survival rates were 72%, 45%, and 77%, respectively. CONCLUSIONS: Limb-sparing
      conservative surgery is possible in the majority of patients with isolated
      locally recurrent STS. Durable local control can be established with
      individualized local treatment strategies. These results support aggressive
      multimodality limb-sparing treatment approaches for these patients.

PMID- 9626318
TI  - Pelvic nerve grafts restore bladder function in denervated rats.
AB  - BACKGROUND: Autonomic nerve preservation techniques for use during surgery for
      rectal cancer have improved. Nevertheless, in some patients pelvic nerves must be
      sacrificed to excise all tumor. For these patients, nerve reconstruction at the
      time of operation by using nerve grafting would be useful. A rat model of this
      type of nerve reconstruction is described. METHODS: Animals were divided into
      three groups. In the sham control group, a pelvic exploration was conducted
      without division of the pelvic nerves. In the nerve ablation group, both pelvic
      nerves were excised segmentally. In the graft group, both pelvic nerves were
      excised and genitofemoral nerves were interposed bilaterally. At 2-week intervals
      postoperatively, animals from each group underwent cystometry under urethane
      anesthesia and neuronal tracing using fragment C of tetanus toxin for
      demonstration of axonal transport via regenerated nerves. RESULTS: At 6 weeks
      postoperatively, 60% of the grafted animals produced rhythmic contractions of the
      bladder. In neuronal tracing studies at weeks 4 and 6, respectively, 40% and 100%
      of the nerve-grafted rats had labeled neurons in the sacral parasympathetic
      nucleus. CONCLUSIONS: These findings suggest that pelvic nerve grafting in rats
      can successfully restore bladder function after surgical injury. Clinical use of
      pelvic nerve grafting may be indicated for patients whose pelvic nerves must be
      sacrificed to excise all tumor.

PMID- 9626319
TI  - Transient inhibition of CD18-dependent leukocyte functions after hemorrhage and
      polymicrobial sepsis.
AB  - BACKGROUND: The goals were (1) to characterize physiologic changes after a
      combined insult of hemorrhage plus sepsis in a large animal model and (2) to
      determine whether transient inhibition of the neutrophil CD18 adherence receptor
      during fluid resuscitation impairs host defense during recovery from this injury.
      METHODS: Two series of experiments were performed in anesthetized swine. In the
      first series (n = 22), the cecum was ligated and incised immediately before 35%
      hemorrhage. After 1 hour, shed blood plus supplemental fluid was administered to
      restore and stabilize hemodynamics. On the basis of these results, a second
      series examined effects of anti-CD18 (2 mg/kg R15.7; n = 9) or its saline placebo
      (n = 10) administered during fluid resuscitation. RESULTS: In the first series
      the mortality rate was 41% (9 of 22). Early deaths occurred 3.0 +/- 0.8 days
      after injury and were distinguished by significantly lower neutrophil counts on
      resuscitation. Those alive a 7 days had intraabdominal abscesses and bacteremia.
      Alveoli and peribronchial spaces were congested, with edema and fibrin deposition
      in capillaries and alveoli. Livers were congested with biliary stasis. Despite
      these pathologic findings, hemodynamic, electrolyte, and serum enzyme changes
      were minimal. In the second series the mortality rate at 4 days was 30% with
      placebo (3 of 10) versus 33% with anti-CD18 (3 of 9). Lung changes (i.e.,
      pneumonia, pleuritis, thrombosis, and edema) were similar in both groups, but
      liver congestion and hemorrhage were attenuated by anti-CD18. Some aspects of
      host defense were altered by anti-CD18. At 24 and 48 hours the oxidative burst
      potential for circulating granulocytes was 208% +/- 57% and 383% +/- 73% with
      placebo versus 1273% +/- 351% and 762% +/- 226% in anti-CD18. At 72 hours the
      granularity of circulating neutrophils was unchanged from baseline with placebo
      but was reduced to 82% +/- 5% by anti-CD18. At 48 hours lipopolysaccharide-evoked
      tumor necrosis factor production in vitro was reduced to 62% +/- 22% with placebo
      but was increased to 148% +/- 16% with anti-CD18. CONCLUSIONS: Anti-CD18 during
      fluid resuscitation did not increase vulnerability to endogenous pathogens
      because the transient inhibition of neutrophil demargination was balanced by
      enhanced oxidative burst, degranulation, and production of tumor necrosis factor
      in circulating cells later during recovery. Thus a single administration of
      antiadhesion therapy does not worsen posttrauma outcome even if given during
      ongoing sepsis.

PMID- 9626320
TI  - Prolonged hepatic warm ischemia in non-heart-beating donors: protective effects
      of FK506 and a platelet activating factor antagonist in porcine liver
      transplantation.
AB  - BACKGROUND: Prolonged warm ischemic injury in non-heart-beating donors (NHBDs)
      significantly affects hepatic allograft function after liver transplantation
      (LTx). METHODS: The effects of FK506 and the platelet activating factor
      antagonist E5880 on postoperative function of hepatic allografts procured from
      NHBDs were evaluated in porcine orthotopic LTx. In donors, livers were subjected
      to 90 minutes of warm ischemia and a subsequent 4-hour cold preservation. Group 1
      (n = 6) was the untreated control group. In group 2 (n = 4), donors were
      pretreated with FK506 (0.3 mg/kg). In group 3 (n = 4), donors and recipients were
      treated with E5880 (0.3 mg/kg). In group 4 (n = 6), pigs were treated with both
      FK506 and E5880. RESULTS: All of the recipients in group 1 died within 12 hours.
      In groups 2 and 3, half of the recipients survived more than 12 hours. In group
      4, all of the recipients survived more than 2 days (p < 0.01 compared with group
      1). The improved survival seen in group 4 was associated with a reduction in the
      serum concentrations of glutamic oxaloacetic transaminase and lactate, and a
      restoration of hepatic energy charge. CONCLUSIONS: The present study suggests
      that FK506 and E5880 can improve the function of hepatic allografts subjected to
      prolonged warm ischemia in NHBDs, and that the protective effects of the two
      drugs seem to be synergistic.

PMID- 9626321
TI  - Unilateral breast enlargement: four case reports of an "unusual" presentation of
      central vein stenosis in patients undergoing hemodialysis.

PMID- 9626322
TI  - Successful primary repair of complete pancreatic disruption caused by blunt
      abdominal trauma: a report of two cases.

PMID- 9626323
TI  - Inspissated bile syndrome followed by choledochal cyst formation.

PMID- 9626324
TI  - Mediastinal parathyroid cyst causing persistent hyperparathyroidism: case report
      and review of the literature.

PMID- 9626325
TI  - Neuroendocrine tumor of the common hepatic duct: a rare cause of extrahepatic
      jaundice in adolescence.

PMID- 9626326
TI  - Emphysematous gastritis.

PMID- 9626327
TI  - Preoperative optimization of cardiac function using SvO2.

PMID- 9626328
TI  - Treatment of early onset atherosclerosis.

PMID- 9626329
TI  - The reaction of S-nitrosoglutathione with superoxide.
AB  - The nitric oxide (NO)-dependent S-nitrosation of thiols to generate S
      nitrosothiols has been proposed as an important pathway for the metabolism of NO
      in vivo. Although it has been suggested that these S-nitrosated compounds are
      resistant to decomposition by reactive oxygen metabolites (ROMs), very little
      information is available regarding the interaction between S-nitrosothiols and
      ROMs. We found that S-nitrosoglutathione (GSNO) rapidly reacted with O2- to
      generate glutathione disulfide and equimolar quantities of nitrite and nitrate.
      The reaction was second order with respect of GSNO and first order with respect
      of O2- with a rate equation of -d[GSNO]/dt = 2k3[GSNO]2[O2-], where k3 = 3 - 6 x
      10(8) M-2s-1. In addition, the reaction of GSNO with O2- generated a strong
      oxidant as an intermediate capable of oxidizing dihydrorhodamine in the absence
      of the apparent generation of NO. We conclude that O2- may act as a physiological
      modulator of S-nitrosation reactions by directly promoting the decomposition of S
      nitrosothiols.

PMID- 9626330
TI  - Signaling through the B cell antigen receptor regulates discrete steps in the
      antigen processing pathway.
AB  - Antigen processing in B cells is initiated by antigen binding to the surface B
      cell antigen receptor (BCR). The BCR is a signaling receptor which also functions
      to endocytose bound antigen for subsequent intracellular processing and
      presentation with class II molecules. Previously, using subcellular
      fractionation, we showed that although the surface BCR constitutively traffics
      from the cell surface to the class II peptide-loading compartment (IIPLC), cross
      linking the BCR regulates trafficking, resulting in a more rapid movement of the
      BCR to the IIPLC (Song et al., 1995, J. Immunol. 155, 4255). The rate of
      degradation of both the BCR and the bound antigen was also accelerated following
      BCR cross-linking. Here we provide evidence that the effect of cross-linking the
      BCR on antigen processing is in part dependent on signal cascades initiated by
      the BCR. We show that the protein kinase inhibitors Genistein and Chelerythrine,
      which block BCR signaling, reduce BCR-enhanced antigen processing in a dose
      dependent manner. The kinase inhibitors have a small effect on the rate of
      internalization of the BCR and antigen following BCR cross-linking and
      significantly decrease the accelerated trafficking to the IIPLC. The increased
      rate of degradation of the BCR and antigen induced by BCR cross-linking is also
      decreased by the kinase inhibitors. BCR signaling does not appear to have a
      global effect on intracellular membrane trafficking as cross-linking the BCR did
      not alter the rate of trafficking of newly synthesized class II molecules to the
      IIPLC. Thus, the signaling function of the BCR appears to play a significant role
      in regulating discrete steps in the intracellular antigen processing pathway.

PMID- 9626331
TI  - The immunomodulator AS101 restores T(H1) type of response suppressed by Babesia
      rodhaini in BALB/c mice.
AB  - The immunomodulator AS101 has been previously shown to confer protection upon
      BALB/c mice infected with the intraerythrocytic parasite Babesia rodhaini (B.
      rodhaini). The present study focuses on the effect of AS101 administration on the
      acute phase of babesial infection where T helper cell subset patterns-TH1/TH2
      were assessed in heavily infected mice. Secretion of cytokines of the TH1 subset
      (IL-2, IFN-gamma, IL-12) and of the TH2 subset (IL-10, IL-4) as well as TGF-beta
      was measured following the administration of AS101 2 weeks before parasite
      infection. Our results demonstrate that the parasites suppress IL-2 protein and
      IL-12 mRNA and that AS101 upregulates their secretion: IL-2, 8 u/ml vs 34 u/ml,
      respectively; IFN-gamma protein, 2370 pg/ml vs 4777 pg/ml, respectively.
      Conversely, babesial infection results in the upregulation of IL-10 and IL-4
      proteins and TGF-beta transcripts, whereas AS101 downregulates their production:
      IL-10, 1800 pg/ml vs 360 pg/ml, respectively; IL-4, 58.3 pg/ml vs 24.5 pg/ml,
      respectively. A possible escape mechanism induced by B. rodhaini is suggested,
      starting with IL-10 inhibition of macrophage activities leading to a suppression
      of the TH1 response and of IL-2 in particular. It is therefore possible that
      AS101 may protect infected mice by activating cellular-mediated immunity and
      concurrently balancing the TH subset responses. It is suggested that AS101 may be
      effective as an antiparasitic drug.

PMID- 9626332
TI  - Mechanism of gamma sigma T-cell-mediated inhibition of stem cell differentiation
      in vitro: possible relevance for myelosuppression in HIV-infected individuals.
AB  - We investigated whether gamma delta T cells contribute to the suppression of
      myelopoiesis in HIV infection. Freshly isolated gamma delta T cells from HIV
      seropositive patients suppressed CFU-GM growth in vitro. Preactivation of gamma
      delta T cells with IL-2 and/or IL-15 further reduced the number of CFU-GM.
      Natural killer cells and to a lower extent CD4+ and CD8+ cells also inhibited CFU
      GM growth. In contrast to gamma delta T cells, this effect was not dependent on
      IL-15 or IL-2 preactivation. Moreover, no enhanced inhibitory effect of CD56+ and
      CD4+ cells was observed in HIV+ subjects compared to HIV- donors. The
      myelosuppressive effect of supernatants of gamma delta T cells could be inhibited
      by antibodies against IFN-gamma or TNF-alpha. Accordingly, we found increased
      numbers of TNF-alpha or IFN-gamma-secreting CD8+ gamma delta T cells in HIV+
      patients. We conclude that the increased fraction of activated gamma delta T
      cells producing myelosuppressive cytokines might contribute to the
      dyshematopoiesis frequently observed in HIV-infected individuals.

PMID- 9626333
TI  - Cytokine regulation of RANTES production by human retinal pigment epithelial
      cells.
AB  - The mechanism whereby inflammatory cells gain access to the retina in posterior
      intraocular inflammatory disease remains unclear. The chemokine RANTES has the
      potential to influence the migration of memory T cells and monocytes across the
      blood-retinal barrier during inflammatory eye disease. We have therefore examined
      the production of RANTES by cultured human retinal pigment epithelial cells
      (RPE), which form a part of the blood-retinal barrier, in response to cytokines
      likely to be present in the microenvironment. IL-1 beta and TNF alpha stimulated
      RANTES production by these cells. IFN-gamma acted synergistically with TNF alpha
      to increase RANTES production. In contrast, IL-4 downregulated RANTES production
      stimulated by TNF alpha. RT-PCR studies showed that RANTES mRNA from RPE followed
      the same pattern of expression in response to cytokines as did RANTES production
      indicating that RANTES production was controlled at, or prior to, transcription.
      RANTES is produced in vitro by RPE in response to the proinflammatory cytokines
      IL-1 beta, TNF alpha, and IFN-gamma and is therefore likely to play a role in the
      development of the inflammatory eye disease endogenous posterior uveitis.

PMID- 9626334
TI  - Modulation by interferon-gamma of the production and gene expression of IL-1
      receptor antagonist in human neutrophils.
AB  - In this report, we show that interferon-gamma (IFN-gamma) modulates the
      production of IL-1ra in activated human neutrophils. In lipopolysaccharide
      stimulated cells, IFN-gamma increased the release of IL-1ra without modulating IL
      1ra mRNA accumulation; under these conditions, IFN-gamma only marginally enhanced
      IL-1ra de novo synthesis, while IL-1ra was more efficiently secreted. In response
      to the formylated peptide, fMLP, neutrophils released small but significant
      amounts of IL-1ra, yet without an increase in IL-1ra mRNA over constitutive
      levels. Following IFN-gamma treatment, however, the fMLP-elicited IL-1ra
      production was greatly potentiated, and this was accompanied by a transient
      increased accumulation of IL-1ra mRNA. Finally, opsonized yeast particles were
      found to induce IL-1ra formation at late incubation times, and prior treatment of
      neutrophils with IFN-gamma moderately enhanced this response. Collectively, our
      results demonstrate that in neutrophils activated by different classes of
      agonists, IFN-gamma modulates the release of IL-1ra by acting through distinct
      mechanisms.

PMID- 9626335
TI  - Lymphocytes expressing Fc gamma receptors suppress antigen-induced proliferation
      in cells from guinea pigs infected with virulent Mycobacterium tuberculosis.
AB  - The immunomodulatory role of T lymphocytes expressing receptors for the Fc
      portion of IgG (T gamma cells) in BCG-vaccinated guinea pigs following pulmonary
      infection with a low dose of virulent Mycobacterium tuberculosis H37Rv was
      studied. Compared to uninfected animals, guinea pigs infected 2 or 4 weeks
      previously harbored significantly increased percentages of T gamma cells in the
      peripheral blood (twofold increase) and the spleen (50% increase), and at 4 weeks
      had nearly fourfold increases in T gamma cells in bronchotracheal lymph nodes
      draining the infected lungs. Removal of T gamma cells by panning on plastic
      dishes coated with a monoclonal antibody specific for guinea pig Fc gamma R
      resulted in significant increases in proliferative responses of splenocytes to
      Con A and PPD in vitro. Removal of T gamma cells from peripheral blood
      lymphocytes resulted in significantly increased responses to PPD and to
      recombinant mycobacterial hsp 65 and hsp 70 antigens. The isolated T gamma cells
      themselves did not proliferate when stimulated with Con A, PPD, or either of the
      specific mycobacterial antigens, even in the presence of syngeneic accessory
      cells. These results suggest that FcR gamma-bearing T cells may play an important
      immunomodulatory role in pulmonary tuberculosis, principally by suppressing
      antigen-induced proliferation in the rest of the lymphocyte population.

PMID- 9626336
TI  - Adrenal hormone modulation of type 1 and type 2 cytokine production by spleen
      cells: dexamethasone and dehydroepiandrosterone suppress interleukin-2,
      interleukin-4, and interferon-gamma production in vitro.
AB  - Our previous work has documented that physical or psychological stress can alter
      interleukin (IL)-2, IL-4, and interferon (IFN)-gamma production by spleen or
      lymph node cells in vitro. To determine if adrenal hormones might be mediating
      these stress-induced changes in type 1 and type 2 cytokines and immune effector
      functions, we cultured spleen cells in vitro with either the synthetic
      glucocorticoid dexamethasone (DEX) or the putative restorative hormone
      dehydroepiandrosterone (DHEA). Spleen cells were obtained from either young (5-6
      weeks old) or mature (7-8 months old) BALB/c mice that were either unimmunized or
      immunized with the T-cell-dependent antigen keyhole limpet hemocyanin (KLH). We
      determined that DEX suppressed production of all three cytokines examined. DHEA
      was not associated with any enhancement of cytokine production. These data
      challenge the hypothesis that glucocorticoids can differentially regulate Th1
      like versus Th2-like cytokine production. Further, they suggest that in stress
      paradigms in which differential regulation of cytokine production and effector
      function has been observed, other neuroendocrine factors in addition to
      glucocorticoids must be relevant.

PMID- 9626337
TI  - The anagen hair cycle induces systemic immunosuppression of contact
      hypersensitivity in mice.
AB  - Contact hypersensitivity (CHS) to picryl chloride (PCl) is depressed in C57BL/6
      mice when CHS is induced via early anagen skin. We have now further dissected
      this phenomenon in vivo. The elicitation phase for CHS was suppressed when anagen
      was induced 4 days after PCl sensitization of telogen animals. Sensitization of
      mice via abdominal skin with all hair follicles in telogen, and back skin
      follicles in anagen, significantly reduced the magnitude of the ear swelling
      response. Consecutive applications of two sensitizing doses of hapten, first on
      induced anagen back skin and then on telogen abdominal skin 7 days later, failed
      to induce tolerance. Furthermore, spleen cell transfer of sensitized anagen mice
      into telogen mice did not inhibit CHS response in the recipients. The current
      study suggests that a temporary state of systemic hyporesponsiveness, mediated,
      e.g., by hair cycle-dependent production of immunosuppressive cytokines rather
      than hapten-specific T suppressor cell activities, plays a critical role.

PMID- 9626338
TI  - Differential regulation of rejection of small intestinal and skin allografts in
      rats by injection of antibodies to ICAM-1 or the integrins alpha 4, alpha L, or
      beta 2.
AB  - Female Lewis (LEW) rats received orthotopic small intestinal transplantation
      (SIT), or tail skin grafts from female (Lewis x Brown Norway)F1 (LBNF1) rats,
      along with peritransplant portal venous (pv) infusion of LBNF1 bone marrow
      derived dendritic cells derived from male donors. All animals received im
      injection with cyclosporin A (5 mg/kg) for 3 consecutive days following
      transplantation. In some cases rats received intravenous injections, at 2-day
      intervals, with 1 mg of monoclonal antibodies to ICAM-1 or the integrins alpha 4,
      alpha L, or beta 2, or combinations of these reagents. Cells were harvested from
      the recipient rats at different times posttransplantation, and single cell
      suspensions were analyzed by FACS for expression of CD3+, CD4+, CD8+, alpha beta
      TcR+, and gamma delta TcR+ cells. Other tissue samples were used for
      histopathological assessment of rejection. We also investigated donor-specific
      and third-party (Wistar-Furth, Wi) restimulation of host lymphocytes from MLN,
      PLN, and PP for production of different cytokines in vitro. Of the various
      antibodies tested, only anti-alpha 4, but not anti-alpha L, -beta 2, nor -ICAM-1
      led to further increased graft survival of LBNF1 SIT beyond that seen with pv
      infused cells alone (30 days vs 19 days), while the combination of anti-alpha L
      (or beta 2) and ICAM-1 produced further significantly increased survival of skin
      grafts (30 days vs 21 days). For both SIT and skin-grafted animals increased
      graft survival was associated with decreased production of IL-2 and IFN-gamma and
      increased production of IL-4 and IL-10 from tissues local to the graft (PP and
      draining LN, respectively), with less significant alterations in tissues distant
      to the graft (PLN for SIT, and MLN for skin grafts). While, as reported
      previously, pv-immunized SIT rats showed increased gamma delta TCR+ cells within
      the SIT in association with increased graft survival, treatment with anti-alpha 4
      diminished this increase in gamma delta TCR+ cells, while simultaneously
      increasing SIT survival. Nevertheless, the bias toward increased IL-10
      production, and decreased IFN-gamma production, from cells of animals showing
      increased survival was maintained. These data suggest that local graft
      infiltration with gamma delta TCR+ cells following pv immunization is not
      necessary for prolongation of survival in this model system, although functional
      changes in the local cytokines milieu may be important.

PMID- 9626339
TI  - Human papillomavirus DNA and p53 status in penile carcinomas.
AB  - Our study aimed at evaluating the presence of human papillomavirus (HPV) DNA in a
      series of 84 paraffin-embedded (PET) penile carcinomas. We have also investigated
      the presence of p53 mutations in these tumors by immunohistochemistry (IHC),
      single-stranded conformational polymorphism (SSCP) and DNA sequencing. Tissues
      were submitted to amplification of a 268 bp fragment from the beta-globin gene
      and a fragment of the E6 gene of HPV types 6, 11, 16 and 18. Twenty samples (18
      fixed in Bouin's solution and 2 in buffered formalin) were found inadequate and
      were excluded from the analysis. In the remaining 64 tumors, HPV DNA was found in
      26% of the samples. The prevalence of HPV in fresh samples of the same tumors was
      56%. The most prevalent type was HPV 16 in both fresh samples and PET. Isotopic
      in situ hybridization was performed in all PET samples, but only 2 cases were
      positive, 1 for HPV 16 and 1 for HPV 18. Immunohistochemistry with anti-p53 pAb
      1801 antibody showed a positive nuclear reaction over more than 5% of tumor cells
      in 26% of the cases. SSCP of exons 5-8 of the p53 gene was performed on 9 HPV
      positive and 12 HPV-negative specimens. Abnormal mobility was found in 26% of the
      tumors, of which 2 were HPV-positive and 5 HPV-negative. Point mutations were
      detected in p53 exons 6 (1 case), 7 (1 case) and 8 (5 cases), showing that high
      risk type HPVs and mutated p53 may coexist in these tumors. Our data indicate
      that a subset of penile carcinomas are etiologically related to HPV and that an
      overlapping subset may arise from mutational events in the p53 gene.

PMID- 9626340
TI  - Role of reproductive factors on the risk of endometrial cancer.
AB  - We analyzed the role of reproductive factors on the risk of endometrial cancer
      using data from a case-control study conducted in Italy. Cases were 752 women
      with histologically confirmed endometrial cancer < 75 years of age. Controls were
      2,606 patients < 75 years of age admitted for acute, non-gynecological non
      hormone-related, non-neoplastic conditions to the same network of hospitals where
      cases had been identified. In comparison with nulliparae, the risk of endometrial
      cancer tended to be lower in parous women, and the estimated multivariate odds
      ratios (ORs) were 0.9, 0.8 and 0.7, respectively, for women reporting 1, 2 and 3
      or more births (chi(2)(1) trend and 10.21). In comparison with women reporting no
      induced abortion, the ORs of endometrial cancer were 0.6 in women reporting 1 and
      0.4 in those reporting 2 or more induced abortions. When considering parous women
      only, in comparison with women reporting their last birth 20 years before or
      longer, the ORs of endometrial cancer were 0.6 in those reporting their last
      birth 10-19 years before and 0.3 in those reporting their last birth < 10 years
      before. Our results confirm and further quantify a protective role of pregnancy
      on the risk of endometrial cancer and provide insights on the time-risk
      relationship between pregnancy and cancer of corpus uteri.

PMID- 9626341
TI  - Effect of fenretinide on plasma IGF-I and IGFBP-3 in early breast cancer
      patients.
AB  - Growing evidence substantiates the role of the insulin-like growth factor I (IGF
      1) system in breast tumorigenesis. Retinoids have been shown to affect the IGF
      system several experimental models. We extended our previous data on plasma IGF-1
      modulation by the synthetic retinoid fenretinide (4-HPR) and investigated the
      effect of the retinoid on plasma IGF binding protein (BP)-3, the major protein
      binding IGFs. IGF-1 and IGFBP-3 were measured on plasma samples obtained at
      randomization and after an interval of approximately 1 year, from 39 and 33 stage
      1 breast cancer patients assigned to receive 4-HPR, and from 39 and 34 untreated
      controls, respectively. There was a significant decrease in plasma IGF-1 after 4
      HPR administration, whereas no significant change was observed in controls. The
      effect of 4-HPR on IGF-1 levels was modified by menopausal status, inasmuch as
      the decrease in IGF-1 was particularly pronounced in pre-menopausal women,
      whereas the reverse was observed in untreated controls. By contrast, treatment
      induced an increase of IGFBP-3 with respect to controls. As a result of this dual
      effect, the bioavailability of IGF-1 for interaction with receptors at target
      levels further decreased in pre-menopausal 4-HPR treated patients compared with
      controls, suggesting that retinoid administration may result in lower
      concentrations of biologically active IGF-1. Our findings may have important
      implications for the clinical preventive activity of this retinoid.

PMID- 9626342
TI  - A small deletion in the 3'-untranslated region of the cyclin D1/PRAD1/bcl-1
      oncogene in a patient with chronic lymphocytic leukemia.
AB  - The cyclin DI/PRAD1 oncogene, a key regulator of the G1 phase of the cell cycle,
      has been incriminated in the pathogenesis of human neoplasia. Cyclin D1 was also
      demonstrated to be identical to the long-sought bcl-1 oncogene in B-cell
      malignancies with the t(11;14)(q13;q32) translocation. We report here a small
      deletion in the 3'-untranslated portion of the cyclin D1 gene in leukemia cells
      of a patient diagnosed with B-chronic lymphocytic leukemia (CLL), associated with
      overexpression of the corresponding cyclin D1 mRNA. During a Northern blot survey
      of B-cell malignancies, we identified a patient whose CLL cells showed a marked
      increase in 1.5-1.6 kb cyclin D1 mRNA species. Subsequent Southern blot analysis
      showed that genomic DNA from the patient's cells contained an extra band in the
      EcoRI digest, suggesting that one allele of the cyclin D1 gene may be altered.
      Polymerase chain reaction (PCR) analysis of the genomic DNA and direct DNA
      sequencing clearly disclosed that one allele of the cyclin D1 gene was deleted in
      the 3'-untranslated region, which would contribute to an increased stability of
      its mRNA. Reverse transcription-polymerase chain reaction (RT-PCR) analysis and
      direct DNA sequencing revealed that the cyclin D1 mRNA was deleted at the
      corresponding region. This finding provides further evidence for a critical role
      of cyclin D1 in the pathogenesis of B-cell malignancies and highlights a novel
      mechanism, a small deletion in the 3'-untranslated region, responsible for
      deregulation of the cyclin D1 gene in oncogenesis.

PMID- 9626343
TI  - Absence of p53 gene mutations in a tumor panel representative of pilocytic
      astrocytoma diversity using a p53 functional assay.
AB  - Although p53-gene mutations occur with significant frequency in diffuse low-grade
      and high-grade astrocytomas, and are postulated to play an important role in
      tumorigenesis in these cases, the role of the p53 gene in pilocytic astrocytomas
      remains unclear. Published data using DNA-based assays for p53-gene analysis in
      these tumors have shown contradictory results in mutation frequency (0-14%). It
      is not known whether these heterogeneous results stem from the biological
      diversity of this tumor group or from technical problems. To re-evaluate p53-gene
      status in pilocytic tumors, we analyzed 18 tumors chosen to represent the
      clinical and biological heterogeneity of this tumor type with respect to
      anatomical location, patient age, gender, ethnic origin (Caucasian or Japanese)
      and the concomitant occurrence of neurofibromatosis type 1 (NF1). All primary
      tumors were histologically diagnosed as pilocytic astrocytoma (WHO grade I),
      except for one anaplastic pilocytic astrocytoma (WHO grade III) which developed
      in an NF1 patient and recurred as glioblastoma multiforme (WHO grade IV). p53
      mutations were detected using an assay in yeast which tests the transcriptional
      activity of p53 proteins synthesized from tumor mRNA-derived p53-cDNA templates.
      None of 18 tumors, including 3 NF1-related tumors, showed p53-gene mutations
      between and including exons 4 and 11. We conclude that p53-gene mutations are
      extremely rare findings in pilocytic astrocytomas, and are absent even in those
      exceptional cases in which malignant progression of such tumors has occurred.

PMID- 9626344
TI  - Family history and subsite of gastric cancer: data from a case-referent study in
      Japan.
AB  - A comparative case-referent study was conducted using data from the Hospital
      Based Epidemiologic Research Program at Aichi Cancer Center (HERPACC) (Nagoya,
      Japan), with the aim of clarifying the effect of family history on gastric cancer
      by subsite. Our study comprised 995 histologically confirmed gastric cancer cases
      (180 cardia, 430 middle, 365 antrum and 20 unclassified) and a total of 43,846
      non-cancer outpatients at Aichi Cancer Center Hospital between 1988 and 1995.
      Logistic regression was used to calculate odds ratios (ORs) for family history of
      gastric cancer and other cancers, adjusted for age, year and season at first
      hospital visit, habitual smoking, habitual alcohol drinking, regular physical
      exercise, preference for salty food and raw vegetable intake. In both genders, a
      positive family history of gastric cancer was associated with a moderate, but
      statistically significant increase in risk of gastric cancer [OR = 1.51, 95%
      confidence interval (95% CI) = 1.29-1.76], while no association was observed
      between the risk of gastric cancer and a family history of other cancers [OR =
      0.97, 95% CI = 0.84-1.13]. OR increased for the middle and antrum parts of
      gastric cancer, but an increment for the cardiac part was observed only in those
      with a maternal history of gastric cancer. Our results suggest that the risk of
      gastric cancer in relation to family history varies by subsite and, furthermore,
      that the subsite-specific risk of gastric cancer is linked to a maternal history
      of gastric cancer.

PMID- 9626345
TI  - Cyclin D1 and Cyclin E expression in malignant thyroid cells and in human thyroid
      carcinomas.
AB  - Evidence of the involvement of cyclin gene alterations in human cancer is
      growing. In this study, we sought to determine the pattern of expression of
      cyclin D1 and cyclin E in normal and malignant thyroid cells. Quiescent rat
      thyroid cells in culture, induced to synthesize DNA by thyrotropin (TSH),
      expressed cyclin D1 gene after 6 hr and cyclin E gene with a peak at 18 hr from
      the stimulus; K-ras-transformed rat thyroid cells, which grew without addition of
      hormones necessary for normal cell proliferation, expressed elevated levels of
      cyclin D1 and cyclin E, compared with normal differentiated thyroid cells. Human
      benign and malignant thyroid tumors and their relative normal tissues were then
      analyzed. Neither major genetic alterations nor amplifications for cyclin D1 and
      cyclin E genes were found by Southern blot analysis in genomic DNAs extracted
      from all types of thyroid tumors. Moreover, statistical analyses of densitometric
      values from Northern blots did not show increased levels of cyclin D1 and E mRNAs
      in the tumor samples, compared with normal thyroid. Immunohistochemical analyses
      of formalin-fixed paraffin-embedded sections of tissues with specific antibodies
      revealed a prevalent cytoplasmic cyclin E staining in the thyroid tissues
      analyzed. Cyclin D1, instead, was present in the cytoplasm of normal thyroids and
      adenomas, but in 31% of thyroid papillary carcinomas analysed, it was
      overexpressed, with a localization in the nucleus. Our in vivo observations
      suggest that unlike cyclin E, elevated nuclear cyclin D1 expression defines a
      subset of thyroid papillary carcinomas, and might be a contributory factor to
      thyroid tumorigenesis.

PMID- 9626346
TI  - Matrilysin-specific antisense oligonucleotide inhibits liver metastasis of human
      colon cancer cells in a nude mouse model.
AB  - Human colon cancer frequently develops liver metastasis. Matrilysin (MMP-7), the
      smallest member of the matrix metalloproteinase (MMP) family, is commonly
      produced by human colon carcinoma cells and has been suggested to be involved in
      the progression and metastasis of this type of cancer. In the present study, we
      tested the effect of a matrilysin-specific antisense phosphorothioate
      oligonucleotide on liver metastasis of the human colon carcinoma cell line WiDr
      in nude mice. In culture, the antisense oligonucleotide moderately inhibited the
      secretion of matrilysin by WiDr cells. Injection of WiDr cells into the spleen of
      nude mice produced many metastatic tumor nodules in the liver. When the antisense
      oligonucleotide was injected daily into the mice for 11 days, the formation of
      the metastatic tumor nodules was strongly inhibited in a dose-dependent manner.
      An inhibition of liver metastasis of over 70% was obtained at a dose of 120
      micrograms of the oligonucleotide per mouse. The antisense oligonucleotide did
      not inhibit tumor growth in spleen and in liver. A scrambled control
      oligonucleotide had no effect on liver metastasis of WiDr cells. Our results
      demonstrate an important role of matrilysin in liver metastasis of human colon
      cancer and the therapeutic potential of matrilysin antisense oligonucleotides for
      the prevention of metastasis.

PMID- 9626347
TI  - Anti-MUC1 class I restricted CTLs in metastatic breast cancer patients immunized
      with a synthetic MUC1 peptide.
AB  - Sixteen metastatic breast cancer patients were immunized with a low dose (5
      micrograms) of a 16 amino acid MUC1 peptide (GVTSAPDTRPAPGSTA) conjugated to KLH
      (BP16-KLH) plus DETOX adjuvant and evaluated for antibody titers against MUC1
      peptide and KLH and for cytotoxic lymphocyte (CTL) activity using class 1 HLA
      matched MUC1-positive tumor targets. All patients generated strong anti-KLH IgG
      responses. Only 3 patients developed an anti-MUC1 IgG response, which was weak in
      magnitude. As it is controversial whether human cancer patients generate class-1
      restricted CTL against MUC1, we examined anti-MUC1 CTL activity of PBLs following
      4 immunizations with BP16-KLH. The generation of MUC1-specific CTLs required only
      a 6-day in vitro stimulation of patients' T-cells with synthetic MUC1-peptide
      pulsed autologous APCs. The assay for CTL activity was a 4 hour 51Cr release from
      labeled adenocarcinoma target cells. Eleven of the 16 immunized patients were
      tested for CTL activity using class-1-matched adenocarcinoma target cell lines.
      Evidence for class-1-restricted killing of MUC1-expressing tumor cell lines was
      obtained in 7 of these 11 patients.

PMID- 9626348
TI  - Isolation of blood-borne epithelium-derived c-erbB-2 oncoprotein-positive
      clustered cells from the peripheral blood of breast cancer patients.
AB  - Clinical studies including thousands of breast cancer patients have shown that c
      erbB-2 is amplified and overexpressed in 20-30% of invasive human breast cancers
      and that it is associated with distant metastasis in specified patient subgroups.
      To isolate and characterize hematogeneously spreading c-erbB-2-positive
      epithelium-derived cells from the peripheral blood of breast cancer patients, a
      combined buoyant density gradient and immuno-magnetic separation method has been
      used. The method utilizes a biotinylated anti-cytokeratin monoclonal antibody
      (MAb) for capturing the epithelium-derived cells. The expression of c-erbB-2 by
      the captured cells was detected using an anti-c-erbB-2 rabbit antibody (21N)
      coupled to an anti-rabbit gold-labeled anti-body, whereby immunoenzymatic
      cytokeratin staining was performed using a silver-enhanced immunogold double
      staining protocol. In total, 29 of the 46 patients tested had either cytokeratin
      (24/29) or cytokeratin/c-erbB-2 (19/29) positive clustered cells in their
      peripheral blood. We thus report here the presence and the frequency of clone
      specifically stained clustered cells in the peripheral blood of breast cancer
      patients. The frequency of cytokeratin/c-erbB2 double-positive clustered cells in
      the peripheral blood was on average 10 times higher than that of double-positive
      single cells. The numbers of cytokeratin/c-erbB-2 double-positive clustered cells
      were positively correlated with the stage of tumors. Results of in vitro motility
      experiments using single and clustered cells from primary breast cancer tissue
      strongly support the assumption that cytokeratin/c-erbB-2 double-positive
      clustered cells have a high potential for locomotion. We suggest that blood-borne
      epithelium-derived c-erbB-2-positive clustered cells are the possible precursor
      cells responsible for the formation of distant metastases and bone marrow
      micrometastases.

PMID- 9626349
TI  - Urokinase-type-plasminogen-activator (uPA) production by human breast (myo)
      fibroblasts in vitro: influence of transforming growth factor-beta(1) (TGF
      beta(1)) compared with factor(s) released by human epithelial-carcinoma cells.
AB  - The urokinase-type plasminogen activator (uPA) may be considered as a key enzyme
      in the processes of cancer cell invasion and metastasis. Evidence has been
      presented that, in breast stroma, uPA is expressed predominantly by
      myofibroblasts located at the invasive areas of the tumor. To examine whether
      transforming growth factor type-1 (TGF beta(1)) produced by breast-carcinoma
      cells is a candidate responsible for the induction of uPA-producing
      myofibroblasts, we studied in vitro the capacity of normal and tumor-derived
      human breast fibroblasts to express uPA and the myofibroblast marker alpha-smooth
      muscle actin in response to TGF beta(1). Next, we compared these influences with
      those elicited by factor(s) released by epithelial-cancer cells. In all 8
      fibroblast strains tested, TGF beta(1) induced a similar concentration-dependent
      increase in the fraction of alpha-smooth-muscle-actin-positive fibroblasts. While
      uPA expression was decreased by TGF beta(1) in most of the fibroblast strains, 2
      strains were relatively insensitive to TGF beta(1) in this respect. Although
      factors present in media conditioned by non-uPA-producing epithelial-tumor cells
      could trigger fibroblasts to become potent producers of uPA, the TGF beta(1)
      content of the conditioned media were linked to the differential effects of
      externally added TGF beta(1) with respect to uPA expression. The data demonstrate
      that, although fibroblasts may utilize TGF beta(1) secreted by tumor cells to
      differentiate into myofibroblasts, tumor cells secrete factor(s) other than TGF
      beta(1) ultimately responsible for the generation of powerful uPA-producing
      fibroblasts.

PMID- 9626350
TI  - VEGF, bFGF and EGF in the angiogenesis of human melanoma xenografts.
AB  - Vascular endothelial growth factor (VEGF) is a major inducer of angiogenesis in
      tumors. Basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF)
      have both been shown to interact with VEGF. The involvement of VEGF, bFGF, and
      EGF in melanoma angiogenesis was investigated here. Four human melanoma cell
      lines (A-07, D-12, R-18, U-25) were included in the study. Angiogenesis was
      quantified by scoring of tumor-oriented capillaries following intradermal cell
      inoculation in BALB/c nu/nu mice. VEGF, bFGF and EGF expression and secretion
      were investigated by Western blotting and enzyme-linked immunosorbent assay,
      respectively. Immunohistochemistry of xenografts grown intradermally was used to
      reveal VEGF and bFGF localization in vivo. The rate of angiogenesis differed
      substantially among the melanoma lines; the sequence from a high to low rate of
      angiogenesis was: A-07, D-12, R-18, U-25. A-07, which induced the highest rate of
      angiogenesis, showed a higher rate of VEGF secretion, stronger VEGF staining by
      immunohistochemistry and higher bFGF expression than the other lines. U-25, which
      induced the lowest rate of angiogenesis, showed a higher rate of VEGF secretion
      than D-12 and R-18. A-07 was the only line that showed detectable bFGF secretion,
      and R-18 was the only line that showed detectable EGF secretion. VEGF is probably
      important in the angiogenesis of melanomas. However, heterogeneity in rate of
      angiogenesis among melanomas cannot be attributed to heterogeneity in rate of
      secretion of VEGF, bFGF and/or EGF only.

PMID- 9626351
TI  - Long circulating half-life and high tumor selectivity of the photosensitizer meta
      tetrahydroxyphenylchlorin conjugated to polyethylene glycol in nude mice grafted
      with a human colon carcinoma.
AB  - In a mode of nude mice bearing a human colon carcinoma xenograft, the
      biodistribution and tumor localization of metatetrahydroxyphenylchlorin (m-THPC)
      coupled to polyethylene glycol (PEG) were compared with those of the free form of
      this photosensitizer used in photodynamic therapy (PDT). At different times after
      i.v. injection of both forms of 125I-labeled photosensitizer, m-THPC-PEG gave on
      average a 2-fold higher tumor uptake than free m-THPC. In addition, at early
      times after injection, m-THPC-PEG showed a 2-fold longer blood circulating half
      life and a 4-fold lower liver uptake than free m-THPC. The tumor to normal tissue
      ratios of radioactivity concentrations were always higher for m-THPC-PEG than for
      free m-THPC at any time point studied from 2 to 96 hr post-injection. Significant
      coefficients of correlation between direct fluorescence measurements and
      radioactivity counting were obtained within each organ tested. Fluorescence
      microscopy studies showed that m-THPC-PEG was preferentially localized near the
      tumor vessels, whereas m-THPC was more diffusely distributed inside the tumor
      tissue. To verify whether m-THPC-PEG conjugate remained phototoxic in vivo, PDT
      experiments were performed 72 hr after injection and showed that m-THPC-PEG was
      as potent as free m-THPC in the induction of tumor regression provided that the
      irradiation does for m-THPC-PEG conjugate was adapted to a well-tolerated 2-fold
      higher level. The overall results demonstrate first the possibility of improving
      the in vivo tumor localization of a hydrophobic dye used for PDT by coupling it
      to PEG and second that a photosensitizer conjugated to a macromolecule can remain
      phototoxic in vivo.

PMID- 9626352
TI  - Stage and organ dependent effects of 1-O-hexyl-2,3,5-trimethylhydroquinone,
      ascorbic acid derivatives, n-heptadecane-8-10-dione and phenylethyl
      isothiocyanate in a rat multiorgan carcinogenesis model.
AB  - The effects of 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ),
      phenylethylisothiocyanate (PEITC), 3-O-ethylascorbic acid, 3-O
      dodecylcarbomethylascorbic acid and n-heptadecane-8, 10-dione were analyzed in a
      rat multiorgan carcinogenesis model. Groups of 15 animals were given a single
      intraperitoneal (i.p.) injection of diethylnitrosamine and 4 i.p. injections of N
      methylnitrosourea as well as N-butyl-N-(4-hydroxybutyl) nitrosamine in the
      drinking water during the first 2 weeks. Then 4 subcutaneous (s.c.) injections of
      dimethylhydrazine and 2,2'-dihydroxy-di-n-propylnitrosamine were given in the
      drinking water over the next 2 weeks for initiation. Test compounds were
      administered during the initiation or post-initiation periods. The dietary dose
      was 1% except for n-heptadecane-8, 10-dione and PEITC (0.1%). Complete autopsy
      was performed at the end of experimental week 28. All 5 compounds reduced the
      number of lung hyperplasia, particularly PEITC when given during the initiation
      period. In addition, HTHQ lowered the incidence of esophageal hyperplasia in the
      initiation period, and of small and large intestinal adenomas in the post
      initiation period. However, it also enhanced the development of hyperplasia and
      papilloma in the forestomach and tongue. PEITC lowered the induction of
      esophageal hyperplasia, kidney atypical tubules and liver glutathione S
      transferase placental form (GST-P)-positive foci when given during the initiation
      period but enhanced the development of liver GST-P positive foci and urinary
      bladder tumors in the post-initiation period. Moreover, it induced hyperplasia of
      the urinary bladder. Our results indicate minor adverse effects for HTHQ in the
      forestomach and tongue, and demonstrate that PEITC, which inhibits carcinogenesis
      at the initiation stage in several organs, also exhibits promotion potential in
      liver and urinary bladder in the post-initiation stage under the present
      experimental conditions.

PMID- 9626353
TI  - Functional intracellular P-glycoprotein.
AB  - Efflux of chemotherapy drugs by P-glycoprotein (P-gp) at the plasma membrane is
      thought to be a major cause of cancer multidrug resistance. In this report, we
      show by flow cytometry that P-gp also concentrates large amounts of 2 different
      drugs, Hoechst 33342 and daunorubicin, within a cytoplasmic compartment of
      multidrug resistant CHRC5 cells. A quantitative assay of Hoechst 33342 revealed
      that cytoplasmic sequestration by P-gp in CHRC5 cells accounted for about half of
      the amount of Hoechst 33342 accumulated by the drug-sensitive parental Aux BI
      cells. Daunorubicin sequestered in the cytoplasm of CHRC5 cells could be released
      by inhibiting P-gp function with cyclosporin A, resulting in cell death. A likely
      site of drug sequestration is P-gp-containing cytoplasmic vesicles, in which the
      P-gp is oriented so that drugs are transported and concentrated in the interior
      of the vesicles. P-gp was detected in the membranes of cytoplasmic vesicles of
      CHRC5 cells by confocal immunofluorescence microscopy and immunoelectron
      microscopy with anti-P-gp monoclonal antibodies (MAbs). Vesicular localization of
      daunorubicin was observed by epifluorescence microscopy. The origin and nature of
      the P-gp-containing vesicles are unknown, but they do not correspond to endocytic
      vesicles. Our results directly demonstrate that chemosensitizer-induced release
      of drugs sequestered in cytoplasmic vesicles by P-gp can be used to overcome
      multidrug resistance.

PMID- 9626354
TI  - Relationship of stable integration of herpes simplex virus-2 Bg/II N subfragment
      Xho2 to malignant transformation of human papillomavirus-immortalized cervical
      keratinocytes.
AB  - Transfection of the right end Xho2 subfragment of Bg/II N of herpes simplex virus
      2 (HSV-2) into human genital keratinocytes immortalized by human papillomavirus
      (HPV) type 16 or 18 resulted in invasive and noninvasive indolent cystic squamous
      carcinomas when cells were injected into immunocompromised mice. Retention and
      expression of the right end portion of the Bg/II N fragment correlated with
      malignancy, as the corresponding HSV-2 sequences were integrated and transcribed
      in the tumorigenic cell lines. HPV-immortalized cells alone were not tumorigenic.
      In contrast, previous results have shown that using the entire Bg/II N region can
      malignantly transform HPV-immortalized cells, although HSV2 DNA was not retained.
      Together, these observations localize the transforming activity of Bg/II N to
      Xho2 and suggest that the remaining sequences have an inhibitory effect on stable
      integration. The Xho2 sequence is 2480 bp long and contains an open reading frame
      (ORF) extending from nucleotides 559 to 1797. The ORF encodes a putative protein
      of 412-aa with a m.w. of 42-43 kDa and is highly homologous to UL43 of HSV-I. The
      correlation of tumorigenicity with stable integration and expression of Xho2 DNA
      in HPV-immortalized cells indicates that HSV-2 should be investigated further for
      a possible role in cervical cancer.

PMID- 9626355
TI  - Photosensitizing effects of m-tetrahydroxyphenylchlorin on human tumor
      xenografts: correlation with sensitizer uptake, tumor doubling time and tumor
      histology.
AB  - The photodynamic effects of m-tetrahydroxyphenylchlorin (mTHPC) were assessed on
      human malignant mesothelioma, squamous cell carcinoma and adenocarcinoma
      xenografts grown in nude mice and were correlated with mTHPC uptake, histology
      and doubling time of the tumors. Non-thermal laser light was delivered to the
      tumor as surface radiation 4 days after intraperitoneal administration of 0.1 and
      0.3 mg mTHPC/kg body weight, respectively. The extent of tumor necrosis was
      measured by histomorphometry. The mTHPC concentration in non-irradiated tumors
      was assessed by high-performance liquid chromatography (HPLC). The tumors were
      graded according to their doubling time and their vascular architecture as
      assessed by histology. The 0.1 mg/kg dose of mTHPC resulted in an equal uptake
      for all 3 tumor types but revealed a larger extent of photosensitized necrosis
      for adenocarcinoma, which displayed a delicate tumor stroma with numerous small
      capillary vessels, than for mesothelioma and squamous cell carcinoma, which were
      both poor in stroma and vessels. The 0.3 mg/kg dose of mTHPC resulted in a 2-fold
      higher tumor uptake for all 3 tumor types and in a larger extent of necrosis for
      mesothelioma and squamous cell carcinoma, but not for adenocarcinoma xenografts,
      compared with the lower drug dose. Our results demonstrate that different tumor
      xenografts respond differently to mTHPC-PDT for a given drug-light condition. In
      this setting, the photosensitizing effect was more closely related to the
      vascular architecture of the tumors than to the sensitizer uptake and doubling
      time of the different tumors

PMID- 9626356
TI  - Mouse mucin 1 (MUC1) defined by monoclonal antibodies.
AB  - Mucins are highly expressed in many different human cancers and numerous murine
      monoclonal antibodies (MAbs) to human mucins, particularly Mucin 1 (MUC1), have
      been produced. However, no such antibodies to murine mucin 1 (muc1) have been
      described and we now describe 6 different antibodies produced to murine muc1 and
      to human MUC1 cytoplasmic tail, either by immunising rats, or muc1 o/o mice with
      synthetic peptides or a fusion protein composed of glutathione-s-transferase
      (GST) linked to the tandem repeat region of muc1. The antibodies to both the
      extracellular tandem repeat region and to the cytoplasmic tail were found to
      react with mucin-containing murine tissues such as breast, stomach, colon, ovary,
      kidney and pancreas, and the staining patterns were similar to those found in
      humans. The reagents reacted specifically with muc1 peptides and tissues;
      however, some cross reactivity with other mucin-derived peptides was noted,
      particularly those containing the amino acid sequence TSS. Three different
      epitopes (TSS, TAVLSGTS and LSGTSSP) of the M30, M70 and MFP25 MAbs were
      detected. Of interest was the finding that some of the antibodies reacted with
      murine lymphocytes; it was not clear whether these reactions were due to mucin 1
      on mouse lymphocytes (MUC1 was considered to be absent from human lymphocyte), or
      due to cross reaction with a sialic adhesion molecule on lymphocytes. The
      antibodies should prove valuable reagents when studying differentiation and
      expression in murine glandular tissues and the ontogeny of mucin-secreting
      tumours.

PMID- 9626357
TI  - Antitumor activity of methotrexate-albumin conjugates in rats bearing a Walker
      256 carcinoma.
AB  - We have recently reported that albumin accumulates in solid tumors and serves
      there as a source of nitrogen and energy. Methotrexate-albumin conjugates [MTX(I)
      RSA] derivatized at a molar ratio of 1:1 differ favorably from original MTX in
      terms of plasma presence and tumor uptake. The purpose of this study was to
      evaluate the therapeutic efficacy of these novel conjugates in a comparative
      study with low m.w. MTX is Sprague-Dawley rats bearing a Walker-256 carcinoma.
      The maximum tolerated dose (MTD) for MTX and MTX(I)-RSA was determined (2 mg/kg
      based on MTX injected on days 1, 3 and 8). The tumor-bearing rats received
      injections of either the MTD or MTD/2 of MTX, MTX-albumin or mixtures containing
      the MTD/2 or MTD/4 of both MTX and MTX-albumin. No toxic side effects were
      observed. Cure rate and tumor growth retardation were slightly better for the
      conjugate compared with MTX alone in the MTD group (16 complete remissions vs. 14
      of 20 rats). The best results were achieved for the combination treatment with
      MTX and MTX-albumin, with complete remission in all 20 rats. In conclusion, MTX
      albumin conjugates show therapeutic activity in vivo without toxic side effects.
      Additive effects were observed for a combination of MTX-albumin and MTX. These
      effects might be caused by the much longer tumor exposition time of the conjugate
      in conjunction with a different route of uptake (pinocytosis for MTX-albumin vs.
      folate receptors for MTX).

PMID- 9626358
TI  - Increased level of p21 in human ovarian tumors is associated with increased
      expression of cdk2, cyclin A and PCNA.
AB  - We have demonstrated over-expression of the cyclin-dependent kinase inhibitor p21
      in various ovarian-cancer cell lines as well as in ovarian-tumor biopsies. This
      increase in p21 expression relative to that observed in normal ovarian epithelial
      cells is unrelated to proliferation index. In the present study, we found that
      p21 is functional, since the protein extracted from IGROVI cells is still able to
      inhibit cdk2-kinase activity. We then investigated how IGROVI cells overcome the
      growth-inhibitory function of p21. Immunofluorescence assays and subcellular
      fractionation showed that p21 is located in cytoplasm and nucleus both in normal
      and in tumoral cells. Compared with normal ovarian epithelial cells in culture,
      the increase in level of p21 in IGROVI cells was found to be associated with
      increased expression of cdk2, cyclin-A and PCNA proteins. In IGROVI cells, p21 is
      associated with inactive cdk2/cyclin-A complex, indicating that it acts as an
      inhibitory factor rather than an assembly factor. Over-expression of cdk2 and of
      cyclin A observed in IGROVI cells allows them to escape to p21-inhibitory
      activity. The fact that cells from ovarian-tumor biopsies exhibited a concomitant
      increase in p21 and in its partners cdk2 and PCNA suggest that ovarian-tumor
      cells can tolerate high levels of functional p21 via over-expression of other
      cell-cycle-regulatory proteins.

PMID- 9626359
TI  - Suppression of growth of hepatocellular carcinoma by sodium butyrate in vitro and
      in vivo.
AB  - Treatment of HuH-7 human hepatocellular carcinoma (HCC) cells with 1-10 mM sodium
      butyrate (SB) resulted in growth inhibition in a dose-dependent manner. At 3 mM
      and higher concentrations, SB caused nuclear fragmentation and DNA ladder
      formation characteristic of apoptosis. In the treated cells, the expression of
      p21 (WAFI/CIPI) increased and that of alpha-fetoprotein (AFP) decreased. These
      characteristic changes were also observed with 5 other human HCC cell lines with
      or without mutation of the p53 gene. The ability of these cells to form colonies
      in soft agar was suppressed by either pretreating the cells with SB prior to soft
      agar plating or incubating untreated cells in SB-containing soft agar. Direct
      injection of SB into tumors developed from HuH-7 cells in nude mice resulted in
      an increase in the p21 level, a decrease in the tumor size and an increase in the
      survival time of mice. When the inoculation of HuH-7 cells into nude mice was
      immediately followed by subcutaneous injection of SB, development of tumors was
      either significantly delayed or completely suppressed. These results suggest that
      SB induces cellular differentiation and suppresses growth and tumorigenicity of
      HCC cells in vitro and in viva by a mechanism independent of p53 but possibly
      dependent on p21.

PMID- 9626360
TI  - LAGE-1, a new gene with tumor specificity.
AB  - Representational difference analysis was used to identify genes that are
      expressed in a human melanoma cell line and not in normal skin. A cDNA clone that
      appeared to be specific for tumors was obtained and the corresponding gene was
      sequenced. This new gene was named LAGE-I. Using a LAGE-I probe to screen a cDNA
      library from the same melanoma cell line, we identified a closely related gene,
      which proved to be identical to NY-ESO-I, a gene recently reported to code for an
      antigen recognized by autologous antibodies in an esophageal squamous cell
      carcinoma. Gene LAGE-I maps to Xq28. It comprises 3 exons. Alternative splicing
      produces 2 major transcripts encoding polypeptides of 210 and 180 residues,
      respectively. Expression of LAGE-I was observed in 25-50% of tumor samples of
      melanomas, non-small-cell lung carcinomas, bladder, prostate and head and neck
      cancers. The only normal tissue that expressed the gene was testis. As for MAGE
      AI, expression of LAGE-I is induced by deoxy-azacytidine in lymphoblastoid cells,
      suggesting that tumoral expression is due to demethylation. The expression of
      LAGE-I is strongly correlated with that of NY-ESO-I. It is also clearly
      correlated with the expression of MAGE genes.

PMID- 9626361
TI  - bcl-2 rearrangement detected by pulsed-field gel electrophoresis (PFGF) in B
      chronic lymphocytic leukemia (CLL) cells.
AB  - B-chronic lymphocytic leukemia (CLL) is characterized by an accumulation of long
      lived, resting B cells expressing the Bcl-2 protein. However, less than 10% of
      the CLL patients shows bcl-2 gene rearrangement in blood cells, using traditional
      Southern blotting analysis. In the present study, rearrangement of the bcl-2 gene
      in CLL cells was studied by pulsed-field gel electrophoresis (PFGE). With this
      method, large DNA fragments (> 50-10,000 kb) could be analyzed. Blood CLL cells
      from 9 of 9 patients and 2 of 2 CLL cell lines showed rearranged bcl-2 gene. In
      comparison, healthy blood B cells and lymphoblastoid cell lines (LCLs)
      established from normal peripheral blood lymphocytes of the patients showed only
      germ line configuration. Thus, the possibility of restriction fragment length
      polymorphisms (RFLPs) in this gene could be excluded. The primary cell involved
      in CLL might be a progenitor B cell that has accidentally rearranged the bcl-2
      gene. As a consequence, such cells express stable amount of Bcl-2 protein and do
      not enter apoptosis. During prolonged survival, such cells may acquire secondary
      changes including chromosomal translocations and mutations.

PMID- 9626362
TI  - Multiple primary cancers to indicate associations between smoking and cancer
      incidence: Vaud and Neuchatel, Switzerland, 1974-1994.

PMID- 9626363
TI  - Rule revision puts patients at risk, ASHP and others tell HCFA.

PMID- 9626364
TI  - Study finds ADRs in 1 in 15 hospital patients.

PMID- 9626365
TI  - Most hospitals removing KCl concentrate from patient units, ISMP reports.

PMID- 9626366
TI  - Enzyme therapy approved for sucrase deficiency.

PMID- 9626367
TI  - Benefits of intensive antiretroviral therapy documented.

PMID- 9626369
TI  - Researchers report sustained suppression of HIV with nevirapine--didanosine-
      zidovudine.

PMID- 9626370
TI  - PHS report addresses antiretroviral drug use during pregnancy.

PMID- 9626372
TI  - The joint commission's revised sentinel-event policy.

PMID- 9626371
TI  - Study raises questions about corticosteroid use for lung maturation in premature
      infants.

PMID- 9626373
TI  - HCFA's challenge to improve the medication-use process.

PMID- 9626374
TI  - Survey of inpatient counseling by hospital pharmacists.
AB  - A survey was conducted to determine the inpatient-counseling practices of
      hospital pharmacists. A questionnaire about the frequency of inpatient
      counseling, barriers to counseling, and suggestions for increasing the level of
      inpatient counseling was mailed to 667 hospital pharmacists. Recipients were
      asked to rate six attitudinal statements about inpatient counseling. The response
      rate was 30%. The largest group of respondents worked in institutions where
      discharge counseling was provided to specific populations or as needed. Some 67%
      of respondents reported not counseling any patients. Barriers to counseling most
      often cited were lack of time and inadequate staff; facilitators most often cited
      were decentralization and resource availability. The most frequent suggestions
      for increasing the amount of counseling were making changes that provide more
      time, having adequate staff to provide counseling, and having a well-designed
      counseling program in place. Responses about barriers and facilitators varied
      with practice setting and frequency of counseling. On average, pharmacists
      reported a belief that they are the health care professionals most qualified to
      counsel inpatients about medications and that this is their responsibility. More
      than two thirds of the responding hospital pharmacists reported counseling no
      patients; the barrier to counseling most frequently reported was lack of time,
      and the facilitator most often reported was decentralization; on average,
      pharmacists reported that they believed they should have a role in inpatient
      counseling.

PMID- 9626375
TI  - Feasibility and pharmacokinetics of carbamazepine oral loading doses.
AB  - The pharmacokinetics and adverse effects of an oral loading dose of carbamazepine
      administered in tablet or suspension form were studied. Patients on a hospital
      epilepsy unit who were to receive carbamazepine as a discharge medication were
      randomly assigned to receive either an oral 8-mg/kg loading dose of the tablet
      formulation or the same dose of the suspension on an empty stomach. Blood samples
      were drawn before and at intervals up to 12 hours after the loading dose. Adverse
      effects were evaluated subjectively and objectively. Total and free serum
      carbamazepine and carbamazepine-10, 11-epoxide (CBZE) concentrations were
      determined by high-performance liquid chromatography. Six adult patients were
      enrolled in and completed the study. All the patients achieved therapeutic total
      carbamazepine levels; the suspension group did so within two hours and the tablet
      group within five hours. Maximum serum carbamazepine concentrations ranged from
      7.10 to 9.92 mg/L, area under the concentration-versus-time curve from 54.85 to
      82.23 micrograms.hr/L, and terminal elimination half-life from 14.05 to 15.71
      hours. Adverse effects were mild, few, and short-lived; none of the patients
      developed gastrointestinal toxicity. Adverse effects were not associated with
      total or free carbamazepine and CBZE concentrations or with total or free
      CBZE:carbamazepine ratios. An oral loading dose of carbamazepine 8 mg/kg achieved
      therapeutic levels within two hours when given as a suspension and within five
      hours when given as tablets and was well tolerated in all patients.

PMID- 9626376
TI  - Community pharmacist interventions in a capitated pharmacy benefit contract.
AB  - Documented interventions associated with processing prescriptions in a managed
      care environment were analyzed, and a bench-mark for interventions was proposed.
      A retrospective analysis of documented interventions by 31 pharmacies contracted
      by a managed care organization to serve 22,000 Medi-Cal patients was undertaken.
      An intervention consisted of identifying any problem related to a prescription,
      taking action, and recording the problem, action, and outcome on a form. Problems
      were categorized as drug selection issues, clinical issues, errors in
      prescription writing, and patient education issues. A similar process was
      followed for describing actions and outcomes. The data were used as an indicator
      of prescription-related problems in contemporary pharmacies in a managed care
      environment; data from another study were used as an indicator of "ideal"
      pharmacist performance in detecting and resolving problems. The estimated
      intervention rate when pharmacists meeting ideal performance expectations worked
      in a managed care environment was set as a benchmark. The economic impact of drug
      selection interventions was determined as well. Data were retrieved and compiled
      from 595 (93.4%) of 637 interventions performed in 1995, when 93,483 contract
      related prescriptions were processed by the 31 pharmacies. Fifty percent of
      problems related to drug selection issues. The most frequent action was
      contacting the presciber (56.1%). The overall intervention rate was 0.7% (range,
      0-4.1%). It was estimated that 4% of prescriptions would require an intervention;
      two pharmacies met this level. Interventions resulting in prescription change
      realized an average decrease in cost of 65.8%. Community pharmacies under
      contract with a managed care organization intervened on 0.7% of prescriptions,
      but the rate of intervention across pharmacies was inconsistent, ranging from 0%
      to 4.1%; a benchmark of 4% would be reasonable.

PMID- 9626377
TI  - Wide-area network connecting a hospital drug informatics center with a
      university.
AB  - A wide-area network (WAN) connecting a new drug informatics center in a
      university-affiliated hospital with the university's campus-based computer
      network is described. In 1994 a pharmacy school developed a drug informatics
      center in an affiliated hospital. The center was originally designed around a
      local-area network (LAN) to be located at the hospital and planned to provide
      clients with easy access to typical productivity software and various electronic
      information resources. Only occasional modem connections to the university
      network were envisioned. However, large price increases in information retrieval
      systems and decreases in the cost of a frame relay connection (T1 line) to the
      campus network led to the installation of a WAN when the drug informatics center
      was established. Technical, political, and legal problems were overcome, and the
      connection was made. The WAN gave faculty and students at the hospital access to
      many of the university's computing and Internet resources. In addition, the
      faculty and students have access to various files and programs available only on
      the drug informatics center's file server at the affiliated hospital. It cost
      about $6500 to install all WAN equipment and maintain the frame relay for the
      first year, or a third of what would have been necessary for information
      retrieval software had a separate LAN been established at the hospital. A WAN
      connecting a drug informatics center and a university's computer network gave the
      center access to more electronic information resources at lower cost than would
      have been possible with a separate LAN.

PMID- 9626378
TI  - Effect of pharmacist interventions on medication use and cost in hospitalized
      patients with or without HIV infection.
AB  - Pharmacotherapeutic interventions and drug acquisition costs in HIV-positive and
      HIV-negative patients on a hospital medical service were studied. In November and
      December 1995, HIV-positive and HIV-negative patients were randomly selected and
      matched on the basis of admission date. Pharmacotherapeutic interventions were
      recorded by a pharmacist until the time of discharge. Drug acquisition costs were
      obtained through records of medications ordered. The two patient groups were
      compared with respect to length of stay (LOS), number and cost of medications,
      and number of interventions. HIV-positive patients had significantly more
      medication orders and required more interventions than HIV-negative patients.
      Mean LOS was not significantly different. HIV status and number of medications
      were significantly associated with requiring five or more interventions. Drug
      acquisition costs were significantly higher in the HIV-positive group. The mean
      pharmacist-attributed cost saving per patient was $134 for HIV-positive patients
      and $27 for HIV-negative patients. HIV-positive patients required more
      interventions and consumed more medication resources than HIV-negative patients.
      Pharmacist interventions produced drug acquisition cost savings for both groups,
      with more savings being realized for positive patients.

PMID- 9626379
TI  - Stability of enalapril maleate in three extemporaneously prepared oral liquids.
AB  - The stability of enalapril 1 mg/mL (as the maleate) in deionized water, citrate
      buffer solution, and a sweetened suspending agent at two temperatures was
      studied. Twenty enalapril 10-mg tablets were crushed to a powder. Deionized
      water, citrate buffer solution, or sweetened vehicle was added to produce three
      200-mL batches of each liquid; the expected final concentration of enalapril in
      each was 1 mg/mL. Each formulation was stored in 10 60-mL bottles, 5 of which
      were stored at 4 degrees C and 5 at 25 degrees C. Samples were collected on days
      0, 7, 14, 28, 42, 56, 70, and 91 for visual inspection and analysis by high
      performance liquid chromatography; pH was measured at each sampling time as well.
      The mean concentration of enalapril in the three liquids at 4 degrees C was > 94%
      of the initial concentration throughout the 91-day study period. At 25 degrees C,
      the mean concentration of enalapril was > 90% for 56 days and > 92% for 91 days
      in both citrate buffer solution and sweetened vehicle. The pH of the liquid
      prepared with deionized water and stored at 25 degrees C decreased by 2.0 pH
      units. Enalapril 1 mg/mL (as the maleate) in three extemporaneously compounded
      oral liquids was stable for 91 days at 4 and 25 degrees C with the exception of
      enalapril in deionized water, which was stable for only 56 days at 25 degrees C.

PMID- 9626380
TI  - Drug-related-injury visits to hospital emergency departments.

PMID- 9626381
TI  - Stability of adenosine 6 micrograms/mL in 0.9% sodium chloride solution.

PMID- 9626382
TI  - Pharmacy-based drug information services in Hong Kong hospitals.

PMID- 9626383
TI  - Treatment of sexual dysfunction induced by selective serotonin-reuptake
      inhibitors.

PMID- 9626384
TI  - Visual compatibility of fentanyl citrate with parenteral nutrient solutions.

PMID- 9626385
TI  - Comparison of electronic drug information resources.

PMID- 9626386
TI  - Response manipulation on the Multiple Affect Adjective Check List-Revised.
AB  - The scoring pattern of the Multiple Affect Adjective Check List-Revised (MAACL-R)
      under both "simulate good" and "simulate bad" conditions and under two
      instructional sets, either "simulate" (Sample 1) or "simulate with caution"
      (Sample 2), was studied in an experiment in which the MAACL-R state form was
      administered to two groups of college students, each consisting of 160
      participants. Each participant was tested twice with both a baseline "actual"
      trial and either a "simulate bad" or "simulate good" trial with the "actual" and
      experimental "simulate" trials counterbalanced. Participants in Sample 2, but not
      Sample 1, received instructions to be "cautious so as not to be detected." As
      expected, the scoring pattern of the MAACL-R was susceptible to response
      manipulation in the predicted directions. However, instructions to "simulate with
      caution" did not produce significantly different scores than did instructions to
      "simulate" alone. In the second study, Receiver Operating Characteristics (ROC)
      was used to determine the utility of each MAACL-R scale to detect response
      simulation. For both "simulate bad" and "simulate good," the PA and PASS scales
      showed the highest correct classification rates. However, detection of simulating
      bad was more accurate than determination of simulating good.

PMID- 9626387
TI  - Bias in the use of standard American norms with Spanish translations of the
      Wechsler Memory Scale-Revised.
AB  - Although most clinicians would readily agree that there is a need for Spanish
      translations and normative samples of major psychological tests because of the
      large number of individuals within the United States whose primary language is
      Spanish, there are in fact few well normed tests applicable to the Spanish
      speaking client in the U.S. As a result, many clinicians administer cognitive
      tests normed on English-speaking American populations translated into Spanish,
      then interpret the test results using the standard American norms. The argument
      is generally made that such a procedure is a reasonable approximation and when
      cautiously interpreted can be useful. The present study investigated the impact
      of this practice by using the Wechsler Memory Scale-Revised (WMS-R) on Spanish
      speaking adults. A group of 50 normal Hispanic Americans aged 25 to 34 years were
      administered the WMS-R translated into Spanish. Results showed that using English
      language standard norms resulted in Spanish-speaking normal individuals getting
      scores an average of 1 standard deviation below "average." These findings were
      present not only for verbal but for nonverbal tests as well. Based on these
      results we strongly argue against the clinical practice of using translations of
      English language tests without renorming and running new validity tests.

PMID- 9626388
TI  - Specificity of the WAIS-R subtests with psychiatric inpatients.
AB  - Subtest specificities were determined for each of the 11 WAIS-R subtests for a
      sample of 200 psychiatric inpatients. The subtest's shared variance (defined as
      the multiple squared correlation between a subtest and all remaining subtests)
      was subtracted from reliable variance (defined as the subtest's reliability) to
      yield a measure of subtest specificity. The Information, Arithmetic, Vocabulary,
      f1p4rehension, Similarities, Picture Arrangement, and Digit Symbol subtests were
      judged to have adequate to ample specificity for ipsative interpretation. The
      Object Assembly, Digit Span, Picture Completion, and Block Design subtests were
      judged to have inadequate specificity for ipsative interpretation. Implications
      for the interpretation of WAIS-R results with psychiatric inpatients are
      discussed.

PMID- 9626389
TI  - Re-examining the factor structure of the Wide Range Assessment of Memory and
      Learning: implications for clinical interpretation.
AB  - The intercorrelation matrices of the standardization sample of the Wide Range
      Assessment of Memory and Learning (WRAML), a multi-component measure of memory
      functioning in children ages 5 to 17 years, were submitted to a hierarchical
      exploratory principal factor analysis (PFA). The PFA solutions were examined and
      compared with the published principal components analysis (PCA) solutions with
      the goal of examining the validity of the clinical scale configuration (Verbal
      Memory, Visual Memory, and Learning) proposed by the test authors. Results of the
      PFA differ from the PCA and do not provide statistical support for the existing
      three-scale structure nor the division between memory and learning. Specific
      factor loadings on the majority of sub-tests are higher than the common factor
      loadings indicating low shared variance. The low communalities together with the
      poor interpretability of the factor structure suggests that the subtests should
      be interpreted clinically as unique entities first and secondarily as factors.
      Theoretical and practical implications of the findings are discussed.

PMID- 9626390
TI  - Factor structure of the State-Trait Anger Expression Inventory for middle-aged
      men and women.
AB  - Recently, Forgays, Forgays, and Spielberger (in press) reported the first
      exploratory factor analysis of the total 44-item State-Trait Anger Expression
      Inventory (STAXI) by gender. The analyses were based on a sample of over 700 male
      and female university students and identified quite well six of the original
      STAXI scales and subscales. In addition, a seventh factor, "Feel-Like-Expressing
      Anger," emerged for women. In the present study, we examined the STAXI responses
      from a middle-aged adult population. Exploratory factor analyses replicated the
      majority of the original structure of the STAXI measure including a Feel-Like
      Expressing-Anger factor for men and women. In addition, we employed confirmatory
      factor analyses and cross-validation procedures to test the validity of
      Spielberger's (1988) AHA! model. Based on these procedures, we found (a) that a
      seven-factor model provided a better fit than a six-factor solution for each
      gender and (b) evidence of robust gender differences for two factors: Feel-Like
      Expressing-Anger and State Anger. These gender differences are consistent with
      the social costs for anger expression in women and the social benefits for men.

PMID- 9626391
TI  - Personality subtypes, coping styles, symptom correlates, and substances of choice
      among a cohort of substance abusers.
AB  - To explore the use of normal personality measures in clinical populations, we
      investigated the usefulness of the Five-Factor personality domains measured by
      the NEO Personality Inventory (NEO-PI) in identifying subtypes among a cohort of
      3,256 substance abusers. Three groups were reliably identified across clustering
      methods and the groups differed in reported coping style, psychopathological
      symptoms, and pattern of substance choice. The largest differences between group
      members' personality dimensions were found for measures of neuroticism,
      agreeableness, and conscientiousness. Members of groups characterized by elevated
      levels of neuroticism demonstrated low levels of conscientiousness and
      agreeableness. The more extreme the group members' levels on these personality
      dimensions, the higher their reported levels of depressive symptoms,
      aggressive/hostile cognitions, impulsiveness, maladaptive coping styles, and
      likelihood of abusing more than one substance. Results support the use of
      measures of normal domains of personality in identifying meaningful subtypes of
      substance abusers.

PMID- 9626392
TI  - Clinical utility of the impact of event scale: psychometrics in the general
      population.
AB  - The Impact of Event Scale (IES; Horowitz, Wilner, & Alvarez, 1979), Trauma
      Symptom Inventory (TSI; Briere, 1995), Los Angeles Symptom Checklist (LASC; Foy,
      Sipprelle, Rueger, & Carroll, 1984), and Traumatic Events Survey (TES; Elliott,
      1992) were administered to a sample of 505 participants from the general
      population. In this application of the IES, participants reported on "an
      upsetting event," as opposed to a specific stressor. The IES was found to be
      reliable and to have concurrent validity with respect to the TSI and LASC. IES
      scores varied as a function of race, but this relationship disappeared once race
      differences in exposure to potentially traumatic events (PTEs) were taken into
      account. Although the IES was predictive of PTEs, the traumatic stress scales of
      the TSI had more predictive and incremental validity than the IES. The current
      data suggest that an "upsetting event" version of the IES may be useful as a
      brief screen for nonarousal-related posttraumatic stress, but that its potential
      limitations should be taken into account. Normative data on this version of the
      IES are presented.

PMID- 9626393
TI  - Interrater reliability of the Ruff Figural Fluency Test.
AB  - To examine interrater reliability of the Ruff Figural Fluency Test (RFFT), 124
      college students completed the RFFT and scored RFFT test protocols. Three
      questions were examined: (a) What is the relationship between RFFT scores
      obtained by different raters? (b) Do participants improve in RFFT scoring
      accuracy with practice?, and (c) Are participants who perform better on the RFFT
      more accurate raters? Interrater reliabilities for unique designs, design
      perseverations, and error ratios were .93, .74, and .66, respectively.
      Participants benefitted from practice on scoring with increased accuracy over
      five protocols. Finally, results indicated a positive relationship between
      performance on the RFFT and scoring accuracy.

PMID- 9626394
TI  - Shipley institute for living scale and the Kaufman Brief Intelligence Test as
      screening instruments for intelligence.
AB  - This study assessed the comparability and acceptability of two tests used to
      screen for overall intelligence levels in adults. At issue is whether either of
      these two tests is preferable for a definable subject population. Participants
      drawn from college (n = 30) and forensic (n = 50) settings completed the Shipley
      Institute for Living Scale (SILS), the Kaufman Brief Intelligence Test (K-BIT),
      and the reading section of the Wide Range Achievement Test-Revised (WRAT-R). The
      correlation between the SILS IQ and the K-BIT IQ scores was .77 for the college
      sample and .83 for the forensic group, with no significant differences between
      SILS and K-BIT mean IQ scores within each sample. Reading level also was
      significantly correlated with SILS and K-BIT IQ scores for both groups. A
      preference for the SILS over the K-BIT was expressed by two overlapping groups:
      college students and above average readers, while a majority of the forensic
      sample and poorer readers chose the K-BIT. Although the SILS and K-BIT yield
      comparable IQ scores within a sample, clinicians may want to consider the
      subject's reading ability, educational history, and feelings and attitudes about
      the assessment situation in deciding which of these two IQ screening tests to
      utilize.

PMID- 9626395
TI  - Discriminant validity of the SCL-90 dimensions of anxiety and depression.
AB  - Although the SCL-90 and other self-report measures of anxiety and depression have
      long been criticized for inadequate factor structure and unacceptably high
      correlations with each other, recent evidence indicates the use of homogeneous
      samples results in greatly improved discriminant validity. This study utilized
      homogeneous samples of anxious (N = 54) or depressed (N = 120) outpatients and a
      factor analysis was conducted on their responses to the depression and anxiety
      items on the SCL-90. Clearly separate factors for anxiety and depression emerged.
      Results are discussed with respect to implication for measures of depression and
      anxiety.

PMID- 9626396
TI  - Fluoride: mode of action.

PMID- 9626397
TI  - Bone morphogenetic proteins: from basic studies to clinical approaches.

PMID- 9626398
TI  - Distinct and overlapping patterns of localization of bone morphogenetic protein
      (BMP) family members and a BMP type II receptor during fracture healing in rats.
AB  - Bone morphogenetic proteins (BMPs) and their receptors (BMPRs) are thought to
      play an important role in bone morphogenesis. The purpose of this study was to
      determine the locations of BMP-2/-4, osteogenic protein-1 (OP-1, also termed BMP
      7), and BMP type II receptor (BMPR-II) during rat fracture healing by
      immunostaining, and thereby elucidate the possible roles of the BMPs and BMPR-II
      in intramembranous ossification and endochondral ossification. In the early stage
      of fracture repair, the expression of BMP-2/-4 and OP-1 was strongly induced in
      the thickened periosteum near the fracture ends, and coincided with an enhanced
      expression of BMPR-II. On day 7 after fracture, staining for BMP-2/-4 and OP-1
      immunostaining was increased in various types of chondrocytes, and was strong in
      fibroblast-like spindle cells and proliferating chondrocytes in endochondral
      bone. On day 14 after fracture, staining with OP-1 antibody disappeared in
      proliferating and mature chondrocytes, while BMP-2/-4 staining continued in
      various types of chondrocytes until the late stage. In the newly formed
      trabecular bone, BMP-2/-4 and OP-1 were present at various levels. BMPR-II was
      actively expressed in both intramembranous ossification and endochondral
      ossification. Additionally, immunostaining for BMP-2/-4 and OP-1 was observed in
      multinucleated osteoclast-like cells on the newly formed trabecular bone, along
      with BMPR-II. In reference to our previous study of BMP type I receptors (BMPR-IA
      and BMPR-IB), BMPR-II was found to be co-localized with BMPR-IA and BMPR-IB. BMP
      2/-4 and OP-1 antibodies exhibited distinct and overlapping immunostaining
      patterns during fracture repair. OP-1 may act predominantly in the initial phase
      of endochondral ossification, while BMP-2/-4 acts throughout this process. Thus,
      these findings suggested that BMPs acting through their BMP receptors may play
      major roles in modulating the sequential events leading to bone formation.

PMID- 9626399
TI  - Opposite effects of recombinant human transforming growth factor-beta 1 on bone
      regeneration in vivo: effects of exclusion of periosteal cells by microporous
      membrane.
AB  - The efficacy of local delivery of recombinant human transforming growth factor
      beta 1 (rhTGF-beta 1) to promote bone regeneration, with or without cellular
      contribution from the periosteum, was evaluated in transosseous defects.
      Implantation of rhTGF-beta 1 into 5 mm in diameter "critical size defects" in the
      rat mandible resulted in a dose-dependent (0.1-20 micrograms/defect) bone
      bridging at both 12 and 24 days, independent of the type of delivery system [3%
      methyl cellulose gel, porous CaCO3 particles, or poly(lactide-co-glycolide)
      beads]. The bridging, however, never exceeded 24% at 12 days or 34% after 24
      days. In contrast, when access of cells from the periosteum to the defect was
      prevented by means of microporous expanded polytetrafluoroethylene barrier
      membranes (GORE-TEX membrane), rhTGF-beta 1 caused a dose-dependent inhibition of
      bone regeneration. The bioactivity of the growth factor was confirmed by
      implantation of 5 or 10 micrograms rhTGF-beta 1 in 12 mm in diameter bicortical
      defects in rabbit calvaria, which resulted in complete bone healing within 28
      days, whereas control defects displayed a bridging of 40%-50%. The findings
      support the concept, based on in vitro experiments by others, that TGF-beta 1
      primarily has a proliferative effect on cells already committed to the
      osteoblastic lineage, but also imply that TGF-beta 1 may be inhibitory to
      induction of osteogenic cells in vivo.

PMID- 9626400
TI  - Expression of bone microsomal casein kinase II, bone sialoprotein, and
      osteopontin during the repair of calvarial defects.
AB  - The temporal expression of bone microsomal casein kinase II, osteopontin, bone
      sialoprotein, alkaline phosphatase, and the accumulation of a solid calcium
      inorganic orthophosphate mineral phase, have been charted from day 2 to day 21
      during the repair of calvarial defects in rats induced by the implantation of
      decalcified rat bone matrix. Unlike the sequence of events that occur when the
      same decalcified bone matrix is implanted subcutaneously or intramuscularly, in
      which cases the first tissue to form in response to the implant is cartilage that
      subsequently calcifies and is later resorbed and replaced by bone, the repair of
      cranial defects is quite different. In the latter case, the first cells induced
      are undifferentiated mesenchymal cells and early fibroblasts followed by
      osteoblastic direct bone formation. Somewhat later a few small islands of
      cartilage are formed, widely separated and spatially distinct from the newly
      formed bone matrix. All of the cartilage and most of the implanted decalcified
      bone matrix are later resorbed and replaced by new bone by day 21. This in vivo
      model of the repair of a bone defect by direct bone formation has provided an
      excellent system to follow specific biochemical and physicochemical events. The
      total accumulation and rate of accumulation of the mineral and the two
      noncollagenous phosphoproteins (bone sialoprotein and osteopontin), as well as
      the activities of alkaline phosphatase, and for the first time either in vivo or
      in cell culture, the activity of microsomal casein kinase II, the major enzyme
      that phosphorylates the bone phosphoproteins, have been determined as a function
      of healing time in vivo. The overall general pattern of accumulation of the
      phosphoproteins and calcium-phosphate mineral phase and their relationships are
      similar to those reported in osteoblast cell cultures also monitored as a
      function of time.

PMID- 9626401
TI  - Morphological changes induced by prostaglandin E in cultured rat osteoblasts.
AB  - Prostaglandin E (PGE)-induced morphological changes of osteoblasts and its
      possible mechanisms were investigated in cultured calvaria and isolated
      osteoblasts from long bone fragments of neonatal rats. The control osteoblasts,
      either on the calvaria or isolated from the long bone fragments, were flat,
      polygonal in shape, and arranged in a monolayer under scanning electron
      microscopy (SEM) or phase contrast microscopy. Treatment with 1 mumol/L of
      prostaglandin E2 (PGE2, 2 h) caused these bone cells to contract a soma, whereas
      10 and 100 mumol/L PGE2 (2 h) caused 18%-30% of the bone cells to elongate and
      expose the undersurface. Incubation of the cultured osteoblasts with PGE2 at
      different time periods showed a bell-shaped pattern with the optimal response at
      2 h of incubation. A similar reaction can be induced by treatment with
      prostaglandin E1 (PGE1) or dibutyryl cyclic adenosine monophosphate (DBcAMP) in
      combination with 3-isobutyl-1-methylxanthine (IBMX). Furthermore, we assessed the
      percentage of responsive isolated bone cells to investigate interactions with
      other agents. The morphological changes induced by PGEs were inhibited by H-8, a
      protein kinase inhibitor. On the other hand, elevated intracellular calcium
      enhanced the PGE-induced morphological changes. Fluorescence labeling showed that
      PGEs caused the breakdown of the actin microfilaments, but spared the
      microtubules and vimentin filaments in the isolated osteoblast-like cells. These
      results suggest that the morphological changes of osteoblasts induced by PGEs may
      be related to the intracellular cAMP and calcium levels.

PMID- 9626402
TI  - Primary human osteoblast proliferation and prostaglandin E2 release in response
      to mechanical strain in vitro.
AB  - The application of mechanical loads to bone cells in vitro has been found to
      generate variable responses, which may in part be due to the source of the cell
      used and the characteristics of the strain applied. The aim of this study was to
      establish a system for applying well-defined physiological levels of mechanical
      strain to a well-defined population of human osteoblast-like cells. Human bone
      derived cells obtained from the greater trochanter of the femur during total hip
      arthroplasty for osteoarthritis were cultured in the presence of 10 nmol/L
      dexamethasone and 100 mumol/L L-ascorbate-2-phosphate. Replicates of cells from
      each patient were loaded on separate occasions using controlled cyclical strains
      of 4000 microstrain (mu epsilon) or less. Strain gauges recorded reliable,
      reproducible strains between 1000 and 6000 mu epsilon. To establish
      reproducibility, sequential explant cultures derived from two patients were
      studied. A consistent increase (p < 0.05) in proliferation between replicates and
      explants derived from one patient subjected to 1600 mu epsilon on separate
      occasions was observed. Cells derived from sequential explants of the second
      patient showed no consistent increase in proliferation between replicates and
      explants. Three of six patients showed a significant increase (p < 0.05) in PGE2
      production after 5 h in response to stretch (4000 mu epsilon) in all replicates
      on separate occasions, whereas, in the other three populations of cells, no
      increase in PGE2 was measured in any of the replicates. These results show that
      the application of highly controlled strains causes a significant effect on human
      bone cells, but only in a proportion of subjects. The response is consistent
      between sequential explants derived from the same patient. The implications of
      this study are that human osteoblast-like cells do respond to physiological
      strain in vitro, although some cells are more strain sensitive than others.

PMID- 9626403
TI  - Expression of an N-methyl-D-aspartate-type receptor by human and rat osteoblasts
      and osteoclasts suggests a novel glutamate signaling pathway in bone.
AB  - Signaling between the various types of cells found in bone is responsible for
      controlling the activity of osteoblasts and osteoclasts, and therefore the
      regulation of bone mass. Our identification of a neuronal glutamate transporter
      in osteoblasts and osteocytes suggests the possibility that bone cells may use
      the excitatory amino acid glutamate as a signaling molecule. In these studies we
      report the expression of different subtypes of glutamate receptors in osteoblasts
      and osteoclasts in vitro and in vivo. We have identified expression in human and
      rat bone cells of N-methyl-D-aspartate receptor-1 (NMDAR-1) and 2D subunits and
      PSD-95, the NMDA receptor clustering protein associated with signaling in the
      central nervous system. In situ hybridization and immunohistochemistry localized
      NMDAR-1 expression to osteoblasts and osteoclasts in human tissue sections. These
      findings strengthen the suggestion that glutamate is involved in signaling
      between bone cells.

PMID- 9626404
TI  - Mechanical properties of ewe vertebral cancellous bone compared with
      histomorphometry and high-resolution computed tomography parameters.
AB  - The goal of the present study was to determine if a high-resolution computed
      tomography (HRCT) system with 150 microns resolution was sufficient to predict
      mechanical properties in ewe lumbar vertebrae. To answer this question, we used a
      triangular comparison between: HRCT; biomechanics (compression and shear tests);
      and histomorphometry, which was the reference method for the measurements of
      morphometric parameters. Two dissected lumbar vertebrae (L-4 and L-5) from 32
      ewes were used. Both compressive and shear properties correlated significantly
      with amount of bone and structural parameters evaluated by histomorphometry (bone
      volume/tissue volume, trabecular thickness, trabecular separation), but no
      significant correlation was found with the trabecular number. With our shear test
      involving the trabecular architecture itself more significant correlations were
      found with the node-strut analysis parameters than from the compressive test.
      Significant correlations were also found between HRCT and histological parameters
      (bone volume/tissue volume, bone surface/bone volume, trabecular separation,
      trabecular number, total strut length, number of nodes, and number of termini).
      Correlations between HRCT structural parameters and mechanical properties on L-4
      were of the same magnitude as the correlations between the histomorphometric
      structural parameters and mechanical results on L-5 but with the remarkable
      advantage the HRCT is a noninvasive method. In spite of the resolution (150
      microns) of our HRCT system, which entailed mainly an enlargement of the thinnest
      trabeculae or their loss during the segmentation process, we obtained coherent
      relationships between mechanical and tomographic parameters. The thinnest
      trabeculae probably had little effect on the mechanical strength. Also, this type
      of resolution allows us to consider the possibility of perfecting an in vivo HRCT
      system. However, physical density and bone mineral density correlated much better
      with strength than either classical histomorphometric or tomographic parameters.
      The current conclusion is fairly negative with respect to the ability of HRCT to
      assess mechanical properties nondestructively as compared with dual-energy X-ray
      absorptiometry. But, the noninvasive nature of the imaging modality and the
      capacity for three-dimensional imaging at arbitrary orientation make HRCT a
      promising tool in the quantitative assessment of cancellous architecture.

PMID- 9626405
TI  - Diagnostic sensitivity of peripheral quantitative computed tomography
      measurements at ultradistal and proximal radius in postmenopausal women.
AB  - Peripheral quantitative computed tomography (pQCT) is a bone densitometry
      technique that is able to provide real volumetric bone density values not only of
      the total but also of trabecular and cortical bone separately. Normal reference
      curves were constructed with cross-sectional data obtained in 275 postmenopausal
      women (50-85 years), measured at 4% of the ulnar length (ultradistal region), and
      data for total, trabecular, and cortical bone density were obtained. In these
      postmenopausal subjects, continuously significant (p < 0.0001) age-dependent
      declines in bone density of 1.14%, 1.1%, and 0.57% for total, trabecular, and
      cortical bone, respectively, were observed while similar declines of 0.9%, 0.9%,
      and 0.4% per year since menopause, respectively, were found. The estimated
      mechanical stability index also showed linear dependencies with decreases of
      0.84%/year and 0.6%/year since menopause (p < 0.0001). A more proximal
      acquisition at 15% of the ulnar length, an almost pure cortical region, resulted
      in linear declines of 0.41%/year and 0.27%/year (p < 0.0001) for the cortical
      bone and the mechanical stability index with significant changes of -0.27% and 
      0.23% per year, respectively, since menopause. Covariance analysis showed similar
      age dependencies of the different bone indices obtained in both regions of
      interest except for the stability index. A significant size adaptation of the
      bone with age was also observed, which was seen in the relationships of the
      trabecular and cortical bone areas to age and to bone density. Diagnostic
      sensitivity of all parameters for established osteoporosis was assessed by
      receiver operating characteristic (ROC) curves, comparing 99 patients with at
      least one fracture to the reference population. The area under these curves was
      highest in the ultradistal pure trabecular density of the radius (75%), followed
      by stability index (72%) and the area of cortical bone (65%) of the proximal
      site. No distinguishing power was seen for the cortical bone density values
      obtained in either the ultradistal (51%) or proximal radius (52%).

PMID- 9626406
TI  - Comparison of ultrasound measurements at the heel between adults with mental
      retardation and control subjects.
AB  - Little is known about the prevalence of metabolic bone disease among adults with
      mental retardation (now known as learning disability), although they may be at
      increased risk of fractures. Broadband-ultrasound attenuation (BUA) and velocity
      of-sound (VOS) measurements were performed on the left heel of 170 patients in a
      large hospital for adults with mental retardation. For 108 of these patients, age
      and gender-matched control subjects were recruited from the local community, who
      also underwent BUA and VOS measurements. The mean age of matched pairs of
      patients and control subjects was 54 (range 32-83) years for men and 53 (range 27
      82) years for women. Mean +/- SEM BUA for male patients was 52 +/- 4 dB/MHz and
      89 +/- 2 for control subjects, whereas for female patients it was 34 +/- 3 dB/MHz
      and 68 +/- 2 for control subjects. VOS was 1603 +/- 7 m/sec for male patients and
      1649 +/- 5 for control subjects, and 1573 +/- 7 m/sec for female patients and
      1623 +/- 5 for control subjects. All differences between patients and control
      subjects were significant (p < 0.005). Dual-energy X-ray absorptiometry bone
      mineral density (BMD) measurements were also performed in seven patients with BUA
      less than 50 dB/MHz, four of whom were found to have a lumbar spine or femoral
      neck BMD more than 2.5 SD below the mean value for young adults. This study shows
      that patients with mental retardation have a marked reduction in BUA and VOS
      measurements at the heel, compared with age-matched control subjects. There is a
      need to identify the major causes of low bone mass in this group, as there may be
      potentially avoidable risk factors for osteoporosis, such as vitamin D deficiency
      and hypogonadism.

PMID- 9626407
TI  - Mechanics of avian fibrous periosteum: tensile and adhesion properties during
      growth.
AB  - We report the results of direct mechanical tests of the fibrous periosteum from
      the tibiotarsi of white leghorn chicks at 4, 6, 8, 9, 10, 11, 12, and 14 weeks of
      age using a newly developed sample isolation technique. Additionally, this
      technique allows the determination of the apparent in vivo load on the fibrous
      periosteum. The periosteum has a highly nonlinear stress-strain relationship at
      all ages. For loading below the in vivo level, the periosteum is pliant and mean
      tensile modulus is 3.35 MPa (+/- 1.84 SD, n = 75). For loading above the in vivo
      level, tensile stiffness is nearly two orders of magnitude greater. In the region
      of high stiffness, mean modulus is 229.5 MPa (+/- 89.6, n = 72). In vivo, the
      periosteum is loaded at the transition between these two stiffness regions. We
      interpret this as indicating that, in vivo, the collagen fibers of the periosteum
      are aligned, but subject to minimal loading. Stress levels in the periosteum
      corresponding to in vivo conditions indicate modest loading, and mean apparent in
      vivo stress levels are 0.92 MPa (+/- 0.37 SD, n = 67). A second technique
      demonstrated that the adhesion of the periosteum in the diaphyseal region (1-6
      weeks of age) is minimal, but is substantial in the metaphyseal region. The
      metaphyseal adhesion will affect the transmission of load between the physes.
      These studies suggest that growth of the fibrous periosteum follows the
      longitudinal growth of the bone, rather than the periosteum having a direct
      mechanical influence on growth plate activity. Comparison of tensile properties
      over the course of growth indicates a substantial increase in periosteal
      stiffness in the early portion of the growth period, which reaches a maximum at
      approximately 9 weeks posthatching. There is also a marked decline in periosteal
      stiffness as growth rate declines in the latest stages of growth (14 weeks). This
      suggests that the basic properties of periosteal collagen may undergo a
      transition during the course of this tissue's brief functional lifetime; that is,
      during long bone growth.

PMID- 9626408
TI  - Volume-referent bone turnover estimated from the interlabel area fraction after
      sequential labeling.
AB  - In the compact bony otic capsule remodeling is low, and bone remodeling units are
      distributed centrifugally in relation to inner ear tissues and spaces.
      Fluorochrome-labeled bone remodeling units are scarce, abortive, and tortuous
      with no uniform direction of movement. This study presents a method for the
      estimation of volume-referent bone turnover based on measurements of the
      fractional area between labels after sequential labeling with osteofluorochromes.
      The applicability of this method is tested against a classical quantification
      method in undecalcified cortical specimens from the canine humerus, where both
      methods can be used. The estimate of bone turnover derived from the new
      sequential labeling in eight dogs is 7.4% (SEM 2.1%) per year and the classic
      estimate derived from calculations of the formative osteonal area and the
      formative period yields 6.9% (SEM 2.1%) per year. Agreement is sufficient to
      justify future measurements of absolute bone turnover in sequentially labeled
      perilabyrinthine bone.

PMID- 9626409
TI  - Gender-related differences in the relationship between densitometric values of
      whole-body bone mineral content and lean body mass in humans between 2 and 87
      years of age.
AB  - The mineral, lean, and fat contents of the human body may be not only
      allometrically but also functionally associated. This report evaluates the
      influence of muscle mass on bone mass and its age-related changes by
      investigating these and other variables in both genders in the different stages
      of reproductive life. We have analyzed the dual-energy X-ray absorptiometry
      (DEXA)-determined whole-body mineral content (TBMC), lean body mass (LBM), and
      fat body mass data (FBM) of 778 children and adolescents of both genders, aged 2
      20 years [previously reported in Bone 16(Suppl.): 393S-399S; 1995], and of 672
      age-matched men and women, aged 20-87 years. Bone mass (as assessed by TBMC) was
      found to be closely and linearly associated with muscle mass (as reflected by
      LBM) throughout life. This relationship was similar in slope and intercept in
      prepubertal boys and girls. However, while keeping the same slope of that
      relationship (50-54 g increase in TBMC per kilogram LBM): (1) both men and women
      stored more mineral per unit of LBM within the reproductive period than before
      puberty (13%-29% and 33%-58%, respectively); (2) women stored more mineral than
      age-matched men with comparable LBM (17%-29%) until menopause; and (3)
      postmenopausal women had lower values of bone mineral than premenopausal women,
      similar to those of men with comparable LBM. Men showed no age effect on the
      TBMC/LBM relationship after puberty. Multiple regression analyses showed that not
      only the LBM, but also the FBM and body height (but not body weight), influenced
      the TBMC, in that decreasing order of determining power. However, neither the FBM
      nor body height could explain the pre/postpubertal and the gender-related
      differences in the TBMC/LBM relationship. Accordingly: (1) calculated TBMC/LBM
      and FBM-adjusted TBMC/LBM ratios were lower in girls and boys from 2-4 years of
      age until puberty; (2) thereafter, females rapidly reached significantly higher
      ratios than age-matched men until menopause; and (3) then, ratios for women and
      age-matched men tended to equalize. A biomechanical explanation of those
      differences is suggested. Sex hormones or related factors could affect the
      threshold of the feedback system that controls bone remodeling to adapt bone
      structure to the strains derived from customary mechanical usage in each region
      of the skeleton (bone "mechanostat"). Questions concerning whether the mineral
      accumulation in women during the reproductive period is related or not to an
      eventual role in pregnancy or lactation, or whether the new bone is stored in
      mechanically optimal or less optimal regions of the skeleton, are open to
      discussion.

PMID- 9626410
TI  - Adhesive capsulitis of the shoulder (frozen shoulder) produces bone loss in the
      affected humerus, but long-term bony recovery is good.
AB  - The objective of the study was to assess the short- and long-term effects of
      adhesive capsulitis (frozen shoulder) on the bone mineral density (BMD) of the
      affected extremity. BMD and clinical status of 22 patients (group A) with active
      phase unilateral adhesive capsulitis and 31 patients (group B) with a previous
      adhesive capsulitis (average 9 years before the examination) were determined. BMD
      was measured from the proximal humerus, humeral shaft, radial shaft, ulnar shaft,
      and distal forearm of both upper extremities using dual-energy X-ray
      absorptiometry (DXA). In group A, the mean BMD of the affected extremity, as
      compared with that of the unaffected side, was significantly lower in the
      proximal humerus (-5.6%; p = 0.001) and humeral shaft (-3.0%; p = 0.008). The
      radial shaft, ulnar shaft, and distal forearm showed no significant side-to-side
      differences. In contrast, in group B, the affected-to-unaffected side BMD
      differences were small and statistically insignificant. Compared with the 31
      patients in group B, the relative side-to-side BMD difference of the 22 patients
      with active-phase disease (group A) was significantly lower in the proximal
      humerus (-5.6% vs. -1.5%, p = 0.009). In the other sites, groups A and B showed
      no significant differences. In conclusion, this study indicates that adhesive
      capsulitis of the shoulder results in significant bone loss in the humerus of the
      affected extremity, but in the long term, capsulitis-induced bone loss shows good
      recovery.

PMID- 9626411
TI  - An interesting case of osteomalacia due to antacid use associated with stainable
      bone aluminum in a patient with normal renal function.
AB  - Antacids containing aluminum and magnesium hydroxide are widely used
      nonprescription agents for treatment of gastritis and peptic ulcer disease. One
      of the side effects of these antacids is that they bind phosphate in the gut,
      resulting in its malabsorption. Short-term use, consistent with the directions on
      the manufacturer's label, is safe and effective for most patients. Heavy chronic
      use, even when within label, can cause serious skeletal impairment. This report
      concerns the case of a 39-year-old pharmacist who self-mediated for peptic ulcer
      disease with high doses of a potent antacid containing aluminum and magnesium
      hydroxide. The patient consumed over 18 kg of elemental aluminum and 15 kg of
      elemental magnesium over 8 years of antacid use. This treatment resulted in the
      clinical syndrome of severe osteomalacia due to profound phosphate depletion.
      Bone biopsy revealed stainable aluminum deposits along 27.6% of the total bone
      surface, which is a unique observation in a patient with normal renal function.
      Treatment included withdrawing the antacid and supplementation with phosphate,
      calcium, and vitamin D. She experienced marked subjective and objective
      improvement with this regimen. This included a striking increase in her bone
      mineral density occurring over the 2-year follow-up period. This case documents
      that long-term antacid therapy, even when used by patients with normal renal
      function and within the manufacturer's label recommendations, can lead to severe
      phosphate depletion, osteomalacia, and toxic accumulation of aluminum and
      magnesium. This clinical syndrome was readily treated by withdrawal of the
      antacid and with calcium and phosphate supplementation. Physicians recommending
      treatment with these compounds or learning of their patient's self-medication
      with them should inform the patient of the potential serious side effects these
      agents can cause when used chronically at maximally recommended doses.

PMID- 9626412
TI  - Are wife abuse and HIV transmission connected?

PMID- 9626413
TI  - A new role model for maternity care.

PMID- 9626414
TI  - What we want. Part 6: Practice tips.

PMID- 9626415
TI  - Hospital care and family physicians.

PMID- 9626416
TI  - Scholarly error.

PMID- 9626417
TI  - Surviving without "McMedicine".

PMID- 9626418
TI  - Antihistamines are safe during the first trimester.

PMID- 9626419
TI  - Ophthaproblem. Glaucomatous damage.

PMID- 9626420
TI  - Dermacase. Herpes zoster.

PMID- 9626421
TI  - Radiology rounds. The appropriate next step would be fine needle aspiration
      biopsy of the nodule.

PMID- 9626422
TI  - Practice tips. Repair of lacerated earlobes.

PMID- 9626423
TI  - Influenza and tetanus immunization. Are adults up-to-date in rural Alberta?
AB  - PURPOSE: To discover what proportion of adults residing within the boundaries of
      a rural health district were up-to-date with influenza and tetanus vaccinations.
      METHODS: A directory-seeded, random digit dial telephone survey of health
      knowledge, attitudes, and practices was conducted in summer 1993. Eligible
      subjects were aged 16 or older, lived within health district boundaries, and
      spoke English. RESULTS: Just over half (57.5%) of people aged 65 and older had
      received influenza vaccine in the previous 12 months, and 55.4% of people 16
      years and older had received tetanus vaccine in the last 10 years (93% of people
      aged 16 to 24 were covered, but only 20.5% of people aged 65 or older). Most
      (89.8%) of those 65 and older knew that influenza vaccine was recommended for
      people their age. Only 59% of respondents knew that influenza vaccine was
      recommended for people with chronic health conditions, regardless of age.
      CONCLUSION: Among adults, coverage with influenza and tetanus vaccines varies
      with age, but is generally unsatisfactory. Rates in this rural area of Alberta
      were similar to Canadian rates for tetanus vaccine coverage but higher for
      influenza vaccine coverage.

PMID- 9626424
TI  - Innovative system to improve use of patient education materials.
AB  - OBJECTIVE: To evaluate a new storage system for patient education materials.
      DESIGN: Anonymous surveys before and after implementation of new storage system.
      SETTING: Family medicine residency teaching centre. PARTICIPANTS: All nurses,
      staff doctors, and first- and second-year residents in the unit. INTERVENTIONS:
      Implementation of a new storage system for patient education materials,
      orientation of all health professionals in the unit to the new system, and
      periodic distribution of patient education newsletters. MAIN OUTCOME MEASURES:
      Self-reported use of patient education materials. RESULTS: Response rates were
      73% (30 of 41 health professionals) in 1990 and 86% (36 of 42) in 1992. Responses
      to the first survey on use of 20 categories of patient education materials showed
      materials were seldom used by most respondents. Back Care, Nutrition, Diabetes,
      VD/Birth Control, and Pregnancy categories were the most frequently used. In the
      second survey, more respondents reported using these five categories of
      pamphlets. Rates of use varied only slightly for the remaining 15 categories.
      CONCLUSIONS: Health professionals reported more frequent use of certain patient
      education materials following implementation of a new storage system.

PMID- 9626425
TI  - Innovative low-risk maternity clinic. Family physicians provide care in Calgary.
AB  - PROBLEM BEING ADDRESSED: Because some family physicians choose to stop providing
      maternity care, many women and their physicians have to seek this care from other
      providers. These providers must respect family physicians' relationships with
      patients and the necessity of returning the family to the referring physician for
      primary care after appropriate maternity and newborn care has been provided.
      OBJECTIVE OF PROGRAM: To design a clinic to address this problem and to deal with
      the practical issues, such as preservation of lifestyle, adequate remuneration,
      and avoiding litigation, family physicians face when they choose to practise
      obstetrics. To provide role models and training opportunities for future family
      physicians. MAIN COMPONENTS OF PROGRAM: Compatibility and cooperation among
      member physicians is essential in order to provide care to a substantial number
      of patients using an established protocol. A well-organized call schedule allows
      clinic physicians to enjoy a reasonable lifestyle. CONCLUSIONS: The clinic,
      established and organized by family physicians, provides family-centred maternity
      care for women and their families when their family physicians choose not to
      practise obstetrics.

PMID- 9626426
TI  - How can second-stage management prevent perineal trauma? Critical review.
AB  - OBJECTIVE: To learn which factors influencing perineal integrity were modifiable
      by physicians and pregnant women. DATA SOURCES: Medical, nursing, and midwifery
      literature was searched mainly for randomized controlled trials. STUDY SELECTION:
      We chose articles on perineal trauma pattern, sexual dysfunction or satisfaction,
      urinary incontinence, and pelvic floor function. We identified 80 papers and
      studied 16 in detail. SYNTHESIS: Five factors affected perineal integrity:
      episiotomy, third-trimester perineal massage, mother's position in second-stage
      labour, method of pushing, and administration of epidural analgesia. Episiotomy
      does not improve perineal outcomes when used routinely. Third-trimester perineal
      massage was discussed only in inadequate studies. Studies comparing position in
      birth chairs and recumbent versus upright positions were inadequate for making
      firm recommendations. Studies of methods of pushing and use of epidural analgesia
      were limited and uncontrolled; no recommendations were possible. CONCLUSION: Only
      limiting episiotomy can be strongly recommended. In the absence of strong data to
      the contrary, women should be encouraged to engage in perineal massage if they
      wish and to adopt the birth positions of their choice. Caretakers should be aware
      of the possibility of interfering with placental function when women hold their
      breath for a long time when pushing.

PMID- 9626427
TI  - Gestational diabetes mellitus. Unresolved issues and future research directions.
AB  - OBJECTIVE: To summarize the controversial aspects of gestational diabetes (GDM)
      and introduce readers to possible relevant research questions that could be
      examined to provide clinicians with good-quality data on which to base decisions
      about this relatively common pregnancy-related issue. DATA SOURCES AND STUDY
      SELECTION: Ongoing review of the English literature related to GDM. Sources were
      not restricted to prospective, controlled trials, as these are severely limited
      in number. SYNTHESIS: Controversial issues include the relevance of GDM to
      clinically meaningful outcomes in the index pregnancy, the effectiveness of
      current therapy in altering these outcomes, and the resultant questionable
      relevance of routine screening and diagnosis of an entity with as yet uncertain
      significance in pregnancy. CONCLUSIONS: Suggested questions to be addressed in
      multicentre controlled trials include randomization with respect to screening and
      with respect to treatment. Until such trials are completed, continuing with a
      standard approach to screening, diagnosis, and treatment, such as that suggested
      by the third international workshop on GDM, is recommended.

PMID- 9626428
TI  - Exercise in pregnancy. Part 1: Update on pathophysiology.
AB  - OBJECTIVE: To review the current data regarding the safety of exercise in
      pregnancy. QUALITY OF EVIDENCE: MEDLINE search was limited to English literature
      between 1987 and 1995 with the key MeSH words exercise and pregnancy. Other
      sources included the Sports and Fitness Database between 1991 and 1995 and a
      manual search for relevant articles. Previous studies on the safety of exercise
      in pregnancy are limited in many ways and exhibit difficulties in controlling for
      confounding factors and in establishing associations while maintaining maternal
      and fetal safety. MAIN FINDINGS: Concerns about the effect of exercise on
      pregnancy include exercise-induced hyperthermia, birth weight changes, fetal
      heart rate responses, miscarriage, labour patterns, maternal injury, and maternal
      weight gain. Exercise during pregnancy also has many potential benefits.
      CONCLUSIONS: Important gaps in our knowledge of exercise and pregnancy remain.
      Available data suggest, however, that moderate exercise on a regular basis during
      a healthy pregnancy has minimal risk for women and their fetuses.

PMID- 9626429
TI  - Exercise in pregnancy. Part 2: Recommendations for individuals.
AB  - OBJECTIVE: To provide practical guidelines for family physicians advising
      exercise in pregnancy. QUALITY OF EVIDENCE: MEDLINE search was limited to the
      English literature between 1987 and 1995 with the key MeSH words exercise and
      pregnancy. Other sources included the Sports and Fitness Database between 1991
      and 1995 and a manual search for relevant articles. MAIN FINDINGS: After
      contraindications to exercise in pregnancy are excluded, the exercise
      prescription depends on the level of maternal fitness; the state of gestation;
      and the mode, intensity, duration, and frequency of exercise. Pregnant women must
      be closely monitored, particularly those who want to maintain vigorous exercise
      programs. CONCLUSIONS: The available data suggest that moderate exercise has
      minimal risk to a woman and her fetus, if the woman is in good health, the
      pregnancy is monitored, and the exercise program is modified as necessary.

PMID- 9626430
TI  - New directions. Escaping early detection is tragic.

PMID- 9626432
TI  - Shunt insufficiency after TIPSS.

PMID- 9626433
TI  - Determination of stent stenosis: an in vivo experimental comparison of
      intravascular ultrasound and angiography with histology.
AB  - PURPOSE: To compare intravascular ultrasound (IVUS) and angiography with
      histology in determining the degree of stent stenosis in an in vivo experiment.
      METHODS: In 16 sheep, a total of 64 stents were implanted into the external iliac
      arteries. Two stents were inserted on either side. Patency was followed by
      angiography and IVUS. Four types of stent were used: two Dacron-covered (Cragg
      Endopro and heparinized Cragg Endopro) and two noncovered (Cragg and Memotherm
      stents). Eight animals were killed after 1 month, eight others after 6 months.
      Histological sections were prepared from the stented vessels. Measurements of the
      patent and total stent diameters determined by IVUS, angiography, and histology
      were compared. RESULTS: Correlation between IVUS and angiography was 0.75,
      between IVUS and histology 0.77, and between angiography and histology 0.85. A
      mean stent stenosis of 17 +/- 11% (range 0-51%) was found on angiography, of 10
      +/- 11% (0-46%) on IVUS, and of 20 +/- 11% (4%-49%) on histology. In comparison
      with histology, IVUS underestimated the degree of stenosis by 10 +/- 8%, and
      angiography underestimated it by 3 +/- 6%. Resolution of IVUS was calculated to
      be about 0.35 mm and that of angiography to be about 0.15 mm. CONCLUSION: Under
      experimental conditions, IVUS was not superior to angiography in determining the
      degree of stent stenosis in long-segment stenoses of iliac artery stents, when
      measurements were correlated with histology. Angiography is sufficient for
      following the patency of iliac artery stents.

PMID- 9626434
TI  - Simulated flow pattern in massive pulmonary embolism: significance for selective
      intrapulmonary thrombolysis.
AB  - PURPOSE: The flow pattern in the central pulmonary arteries proximal to large
      pulmonary emboli was studied experimentally. The currents to which thrombolytic
      agents are exposed when administered via an intrapulmonary catheter were
      visualized in order to explain the lack of benefit of local versus systemic
      administration. METHODS: By illumination of suspended microspheres, the flow
      pattern proximal to an obstructing embolus was visualized in an in vitro
      pulmonary arterial flow model. In six dogs massive pulmonary embolism was
      created. A pigtail catheter was positioned in the pulmonary artery immediately
      proximal to the central edge of the occluding embolus. To allow visualization of
      the local flow pattern, a small amount of contrast material (4 ml) was injected
      through the catheter at a high flow rate (25 ml/sec). The course of the
      radiopaque spot that emerged from the catheter tip within 160 msec was monitored
      with digital subtraction angiography at a frame rate of 12.5 frames/sec. In two
      dogs, the study was repeated after embolus fragmentation with the same catheter
      position. RESULTS: The flow model study revealed formation of a vortex proximal
      to the occluding embolus. In vivo experiments showed that the radiopaque spot was
      whirled by the vortex proximal to the embolus and made only evanescent contact
      with the edge of the embolus. Regardless of the embolus location, the contrast
      spot was washed into the non-occluded ipsilateral and contralateral pulmonary
      arteries within 0.40-0.64 sec. After embolus fragmentation, the contrast spot was
      carried completely into the formerly occluded artery. CONCLUSION: Flow studies
      explain why thrombolytic agents administered via a catheter positioned adjacent
      to the embolus may have no more effect than systemically administered agents. An
      enhanced local effect is precluded by the rapid washout into the non-occluded
      pulmonary arteries and subsequent systemic dilution. These results support the
      practice of direct intrathrombic injection of thrombolytics or local thrombolysis
      as an adjunct to embolus fragmentation.

PMID- 9626435
TI  - Transcatheter arterial embolization for malignant osseous and soft-tissue
      sarcomas. I. A rabbit experimental model.
AB  - PURPOSE: To evaluate the effect of transcatheter arterial embolization (TAE) on
      metastatic bone tumors in an experimental study. METHODS: Fifteen Japanese white
      rabbits were transplanted with VX2 sarcoma cells into the iliac crest. In 10
      rabbits, the arterial supply to the iliac bone tumors, internal iliac artery and
      iliolumbar artery were then embolized with particles of gelatin sponge. The
      therapeutic effect was evaluated by comparison with the natural course of control
      tumors in the other five rabbits. RESULTS: After TAE, extensive necrosis,
      fibrosis, and vacuolization within the tumors were confirmed histologically. In
      the control rabbits, 19% +/- 7% of the entire tumor was found to be spontaneous
      tumor necrosis; in contrast, the tumors of the TAE group showed necrosis as 62%
      +/- 22% of the entire tumor. In one TAE group rabbit, no active tumor cell could
      be detected in the residual tumor. CONCLUSION: TAE was found to be an effective
      treatment for bone tumors in an experimental model.

PMID- 9626436
TI  - Transcatheter arterial embolization for malignant osseous and soft tissue
      sarcomas. II. Clinical results.
AB  - PURPOSE: To evaluate the clinical effects of transcatheter arterial embolization
      (TAE) on malignant bone and soft tissue tumors. METHODS: TAE was performed in 10
      patients with primary bone and soft tissue sarcomas and in 31 patients with
      metastatic bone tumors. The embolized arteries were the internal iliac artery in
      30 cases, the intercostal artery in six cases, the lumbar artery in five cases,
      the suprascapular artery in three cases, and the iliolumbar artery, the internal
      pudendal artery, and the lateral sacral artery in one case each. The embolized
      material was gelatin sponge particles. The chemotherapeutic drugs were usually 20
      40 mg of doxorubicin for primary and metastatic tumors and 50-100 mg of cisplatin
      only for primary tumors. In addition, 50-60 Gy of 10-MV radiotherapy with or
      without radiofrequency (RF)-capacitive hyperthermia in four sessions was
      administered before TAE for primary tumors only. RESULTS: Even though the pain
      score increased immediately after TAE, 30 of 38 (79%) patients with pain (8 of 9
      with primary tumors, and 22 of 29 with metastases) achieved pain control after
      TAE. A necrotic low-density area shown by computed tomography (CT) after TAE was
      found in 31 of 41 (76%) tumors [8 of 10 (80%) with primary tumors, and 23 of 31
      (74%) with metastatic tumors]. The tumor size decreased in 14 of 25 (56%) primary
      and metastatic tumors after 3 months. Osteosclerotic changes appeared in two
      cases of metastatic tumors after 6 months. In five tumors resected after TAE,
      large areas of necrosis within the tumor were confirmed histologically. Transient
      local pain and numbness appeared after TAE, but were relieved by drug treatment
      within 1 week. No severe complications except a case of gluteal muscle necrosis
      were encountered after TAE. The 1-year survival rate of the patients with primary
      tumors was 38.1%, and the median survival was 18 months. The longest survival was
      84 months. The 1-year survival rate of the patients with metastatic bone tumors
      was 38.9%; the median survival was 12 months. The longest survival was 24 months.
      CONCLUSION: TAE could be an effective treatment for pain control and local
      control of malignant bone and soft-tissue tumors.

PMID- 9626437
TI  - Arterial hepatic embolization of unresectable hepatocellular carcinoma using a
      cyanoacrylate/lipiodol mixture.
AB  - PURPOSE: A survival analysis in 16 patients with unresectable hepatocellular
      carcinoma (HCC) undergoing transcatheter arterial embolization (TAE) using a
      combination of lipiodol and N-butyl-2-cyanoacrylate (5:1) was performed in a
      retrospective study. METHODS: A combination of lipiodol and N-butyl-2
      cyanoacrylate (5:1) was used for TAE. All patients had disease compatible with
      Okuda stages I and II. RESULTS: Twenty-four embolizations were done; five
      patients had more than one embolization. Median alpha-fetoprotein levels declined
      from 116 to 48.6 ng/ml. A median of 0.3 ml cyanoacrylate was administered per
      patient. Median survival was 8.5 months (range 2-49 months). After a median
      follow-up of 4 years, 12 patients have died (75%). Okuda stage I and II patients
      had a median survival time of 34.4 and 5.5 months respectively. Few side effects
      (19%) were seen. CONCLUSION: We conclude that the TAE procedure used [lipiodol
      and N-butyl-2-cyanoacrylate (5:1)] is safe and produced only few side effects,
      thus constituting a valuable therapeutic option for patients with Okuda stage I
      and II HCC.

PMID- 9626438
TI  - Early and long-term results of subclavian angioplasty in aortoarteritis (Takayasu
      disease): comparison with atherosclerosis.
AB  - PURPOSE: To compare the early and long-term outcomes of subclavian artery
      angioplasty in patients with aortoarteritis and atherosclerosis. METHODS: Sixty
      one subclavian artery angioplasties were performed in 55 consecutive patients
      with aortoarteritis (n = 32) and atherosclerosis (n = 23) between 1986 and 1995.
      An arch aortogram followed by a selective subclavian artery angiogram was done to
      profile the site and extent of the lesion, its relation to the vertebral artery,
      and the distal circulation. Percutaneous transluminal angioplasty (PTA) was
      performed via the femoral route for 56 stenotic lesions and 5 total occlusions.
      RESULTS: PTA was successful in 52 (92.8%) stenotic lesions and 3 (60%) total
      occlusions. Three patients (5.4%) had complications, that could be effectively
      managed nonsurgically. Compared with atherosclerosis, patients with
      aortoarteritis were younger (27.4 +/- 9.3 years vs 54.5 +/- 10.5 years; p <
      0.001), more often female (75% vs 17.4%; p < 0.001), gangrene was uncommon (0% vs
      17.4%; p < 0.05), and diffuse involvement was seen more often (43.8% vs 4.4%; p <
      0.001). The luminal diameter stenoses were similar before PTA (88.6 +/- 9.7% vs
      89.0 +/- 9.1%; p = NS). Higher balloon inflation pressure was required to dilate
      the lesions of aortoarteritis (9.9 +/- 4.6 ATM vs 5.5 +/- 1.0 ATM; p < 0.001).
      This group had more residual stenosis (15.5 +/- 12.4% vs 8.3 +/- 9.4%; p < 0.05)
      after PTA. There were no neurological sequelae, even in PTA of prevertebral
      lesions. On 3-120 months (mean 43.3 +/- 28.9 months) follow-up of 40 patients,
      restenosis was more often observed in patients with aortoarteritis, particularly
      in those with diffuse arterial narrowing. These lesions could be effectively
      redilated. Clinical symptoms showed marked improvement after successful
      angioplasty. CONCLUSION: Subclavian PTA is safe and can be performed as
      effectively in aortoarteritis as in atherosclerosis, with good long-term results.
      Long-term follow-up shows that it provides good symptomatic relief.

PMID- 9626439
TI  - Long-term results of vena cava filters: experiences with the LGM and the Titanium
      Greenfield devices.
AB  - PURPOSE: Vena cava filter (VCF) application is the method of choice to prevent
      recurrent pulmonary embolism in patients with deep venous thrombosis. Because of
      the reported complications after VCF placement we summarize our long-term follow
      up results with the LGM and Titanium Greenfield (TG) devices. METHODS: Eighty
      seven LGM VCF and 17 TG VCF were placed in 104 patients (average age 64 years).
      The follow-up examinations were performed by color-coded duplex sonography, plain
      radiographs, cavography, and computed tomography (CT). The maximum observation
      time was 81 months. RESULTS: Filter migration occurred in 11% (8/76) of the LGM
      VCF and 15% (2/13) of the TG VCF. Vena cava thrombosis was seen in 17% (13/76) of
      the patients with an LGM VCF and in 31% (4/13) of those with a TG VCF. The
      patency rate was 95% (72/76) for the LGM VCF and 92% (12/13) for the TG VCF.
      Pulmonary embolism was noted in 3 patients after LGM VCF insertion and in no
      patient after TG VCF insertion. CONCLUSION: A VCF should only be inserted in a
      patient after pulmonary embolism and when there is strict proof of the
      indication.

PMID- 9626440
TI  - Peripheral insertion of a central venous access device under fluoroscopic
      guidance using a peripherally accessed system (PAS) port in the forearm.
AB  - PURPOSE: We describe the technique, efficacy, and complications of fluoroscopy
      guided implantation of a central venous access device using a peripherally
      accessed system (PAS) port via the forearm. METHODS: Beginning in July 1994, 105
      central venous access devices were implanted in 104 patients for the long-term
      infusion of antibiotics or antineoplasmic agents, blood products, or parenteral
      nutrition. The devices was inserted under fluoroscopic guidance with real-time
      venography from a peripheral route. RESULTS: All ports were successfully
      implanted. There were no procedure-related complications. No thrombosis or local
      infection was observed; however, in six patients catheter-related phlebitis
      occurred. CONCLUSION: Fluoroscopy-guided implantation of a central venous access
      device using a PAS port via the forearm is safe and efficacious, and injection of
      contrast medium through a peripheral IV catheter before introduction of the
      catheter helps to avoid catheter-related phlebitis.

PMID- 9626441
TI  - Patency and reintervention rates during routine TIPSS surveillance.
AB  - PURPOSE: To assess the medium-term outcome of transjugular intrahepatic
      portosystemic stent shunts (TIPSS) by measuring the incidence of shunt
      obstruction or failure during routine surveillance and the number of
      interventions performed. METHODS: This is a retrospective study covering a 4-year
      period, from 1992 to 1996, during which 102 TIPSS procedures were performed.
      Indications for treatment were variceal bleeding (76%) and refractory ascites
      (24%). Follow-up protocol after TIPSS included transfemoral or transjugular
      portal venography and measurement of portosystemic pressure gradient (PPG) at 3
      months, 12 months, and then at yearly intervals. The results of the first 155
      venograms on 62 patients (mean follow-up 14 months) have been reviewed and Kaplan
      Meier analysis performed. RESULTS: One hundred and thirty-seven of 155 (88%)
      examinations showed patent shunts. Fifty-six of 137 (41%) of the patent TIPSS had
      elevated PPG with signs of stenosis. The majority (41/56) of shunt stenoses with
      elevated pressure gradients were related to neointimal hyperplasia in the hepatic
      venous aspect of the shunt. Interventions used to reduce the pressure gradient or
      to restore patency included: angioplasty (62/102 interventions), additional
      stents (21/102), a second TIPSS procedure (2/102), and thrombolysis or
      thrombectomy (4/102). The primary patency rate was 66% at 1 year (52% at 2
      years). Primary assisted patency was 72% at 1 year (58% at 2 years). Secondary
      patency was 86% at 1 year (63% at 2 years). CONCLUSION: The majority of TIPSS
      shunts will remain patent when regular portal venography, with appropriate
      intervention, is undertaken. Although there is a high reintervention rate this
      mainly takes the form of balloon angioplasty.

PMID- 9626442
TI  - Radiation exposure to interventional radiologists during manual-injection digital
      subtraction angiography.
AB  - PURPOSE: We investigated the relationship between the amount of radiation
      exposure to the operator during table-side manual-injection angiographic
      procedures including digital subtraction angiography (DSA) and the operator's
      position, as well as a simple means to decrease radiation exposure. METHODS:
      Measurement of radiation exposure was carried out with thermoluminescent
      dosimeters (TLDs) in nine abdominal angiographies. In the first study, radiation
      exposure during DSA or during fluoroscopy was measured using TLDs placed near the
      angiographic table. In the second study, radiation exposure to the interventional
      radiologist was measured during manual-injection DSA at a near and a far operator
      position. RESULTS: Radiation exposure to the operator received during manual
      injection DSA accounted for more than 90% of the total procedural exposure. The
      exposure to the operator markedly decreased at the far position compared with
      that at the near position when performing DSA. CONCLUSION: Manual-injection DSA
      is the largest contributor to radiation exposure received by the interventional
      radiologist, therefore, the use of a power injector is always recommended when
      performing DSA. When manual-injection DSA is necessary, radiologists should
      position themselves as far away from the patient as possible.

PMID- 9626443
TI  - Aortoiliac aneurysm with arteriocaval fistula treated by a bifurcated
      endovascular stent-graft.
AB  - A 71-year-old patient with high-output cardiac failure was found to have an
      aneurysmal distal aorta with evidence of an arteriocaval fistula on ultrasound
      scanning. CT demonstrated an aneurysm of the distal aorta and right common iliac
      artery and an intraarterial digital subtraction angiogram confirmed an
      arteriocaval fistula. In view of the patient's cardiac failure and general
      condition an endovascular stent was considered. The right internal iliac artery
      was occluded with Tungsten coils prior to the insertion of a bifurcated stent
      graft. This resulted in total occlusion of the aneurysm and obliteration of the
      arteriocaval fistula. To our knowledge such a case has not been previously
      reported.

PMID- 9626444
TI  - Successful exclusion of subclavian aneurysms with covered nitinol stents.
AB  - Two cases of percutaneous endoluminal exclusion of a subclavian aneurysm with a
      Dacron-coated nitinol stent are presented. One subclavian aneurysm followed
      trauma; the other was due to thoracic outlet stenosis which was caused by a
      cervical rib. In both patients the aneurysm was excluded successfully. The follow
      up periods were 22 and 14 months, respectively. Stenoses at the stent graft
      occurred in both patients; one was treated by balloon angioplasty. In selected
      patients, endoluminal grafting could be an alternative to surgery; however, stent
      graft designs need to be improved and long-term follow-up is awaited.

PMID- 9626445
TI  - Persistence of recruitable coronary collaterals in the absence of coronary
      vasospasm in a patient with variant angina.
AB  - Recruitable coronary collaterals may appear when spasm suddenly occludes the
      coronary artery. We report a patient with variant angina who had visible
      collateral vessels on a control coronary angiogram, despite the presence of
      normally appearing coronary arteries. These collaterals disappeared after
      intracoronary administration of nitroglycerin. These findings suggest that
      recruitable collateral vessels can remain patent long after spontaneous attacks
      of angina have resolved, and become visible when there is a pressure difference
      between two small coronary arteries.

PMID- 9626446
TI  - Cholecystoduodenal fistula: a complication of inserted self-expandable metallic
      biliary stents.
AB  - We encountered a case of hepatic hilar cholangiocarcinoma resulting in
      cholecystoduodenal fistula after insertion of self-expandable metallic biliary
      stents (EMBSs). To our knowledge, there has been no report of cholecystoduodenal
      fistula after insertion of EMBSs. This case suggests that immediate gallbladder
      decompression may be necessary if acute cholecystitis occurs after insertion of
      EMBSs.

PMID- 9626447
TI  - Emergent Z stent placement for treatment of cor pulmonale due to pulmonary emboli
      after failed lytic treatment: technical considerations.
AB  - A patient with a pulmonary embolism due to deep vein thrombosis of a lower
      extremity developed hypotension and cor pulmonale despite prior placement of an
      inferior vena caval filter and treatment with a thrombolytic agent. After failure
      of percutaneous guidewire fragmentation and thrombosuction, self-expandable
      bilateral Z stents were positioned into the lower branches through the pulmonary
      arterial trunks. The patient experienced immediate relief of her cor pulmonale
      and successful recovery from hypotension.

PMID- 9626448
TI  - A triple coaxial catheter system for subselective visceral artery catheterization
      and embolization: preliminary clinical experience.
AB  - We developed a triple coaxial catheter system (TCCS) which consists of a 6.1 Fr
      outer, a 4.1 Fr intermediate, and a 3.0 Fr inner catheter, all coated with a
      lubricant. The TCCS was used in seven patients with hepatic tumors, after several
      attempts to access a targeted vessel with conventional catheters and guidewires
      failed to reach the targeted vessel. No complications were encountered with the
      use of this system. TCCS may be a useful device for selective abdominal
      arteriography.

PMID- 9626449
TI  - Effective treatment of hemospermia by liquid embolization of a small pelvic
      arteriovenous malformation.

PMID- 9626450
TI  - Re: Volleyball-related ischemia of the hand.

PMID- 9626451
TI  - Monitoring of p53 autoantibodies in lung cancer during therapy: relationship to
      response to treatment.
AB  - Alteration of the p53 gene is the most frequent genetic alteration in human
      cancer, and it leads to the accumulation of mutant p53 in the nucleus of tumor
      cells. In addition, it has been shown that patients with various types of
      neoplasias have p53 antibodies in their sera. ELISA was used to detect anti-p53
      antibodies in their sera of 167 patients with lung cancer. Among these, 32
      individuals (16 positive for p53 antibodies and 16 negative) were monitored over
      a period of 30 months for p53 antibodies. Twelve of 16 antibody positive patients
      had reduced titers during chemotherapy that led to partial or complete remissions
      of disease. The specificity of these antibodies was confirmed by two different
      ELISA procedures and by immunoprecipitation. The very rapid, specific decrease in
      these antibodies during therapy suggests that a constant level of tumoral cells
      with nuclear accumulating p53 protein is necessary for a detectable humoral anti
      p53 response. The good correlation found between the specific evolution of the
      p53 antibody titer and the response to therapy suggests that p53 antibodies could
      represent a useful tool for checking the response to therapy and for monitoring
      some relapses before they are clinically detectable.

PMID- 9626452
TI  - Improved targeting of brain tumors using dexrazoxane rescue of topoisomerase II
      combined with supralethal doses of etoposide and teniposide.
AB  - Dexrazoxane (ICRF-187) is a catalytic inhibitor of the nuclear enzyme DNA
      topoisomerase II (topo II). It protects cells against topo II poisons, such as
      etoposide and teniposide, by hindering the DNA cleavage reaction of the target
      enzyme. We have previously shown that this antagonism also extends to an in vivo
      model. Thus, ICRF-187 protected mice against supralethal doses of etoposide and
      amsacrine, and the etoposide LD10 dose increased as much as 3.6-fold when
      combined with ICRF-187 (B. Holm, Cancer Chemother. Pharmacol., 38: 203-209,
      1996). We describe here how scheduling of this drug combination can be optimized
      and used. Interestingly, ICRF-187 can protect when it is given after etoposide.
      Although timing is very critical here, ICRF-187 was able to completely protect
      when given 10 min after etoposide. This rescue principle resembles methotrexate
      rescue by folinic acid. We also found scheduling to be crucial because ICRF-187
      did not protect when etoposide was given once a day for five days, whereas
      effective protection was seen when etoposide was used three times, once every
      four days. Similar investigations were performed with teniposide in combination
      with ICRF-187. The combination with ICRF-187 allowed a 3.4-fold teniposide dose
      escalation. Such dose escalations could be advantageous in specific situations.
      One such case is when the tumor is situated in a pharmacological sanctuary, e.g.,
      in the brain. ICRF-187 is hydrophilic and does not cross the blood-brain barrier,
      whereas the lipophilic etoposide and teniposide do. Therefore, ICRF-187 would
      protect normal tissues and allow a cytotoxic dose of etoposide to reach the
      central nervous system (CNS). We therefore studied the combinations using L1210
      or EHR2 cells inoculated into the CNS of mice. L1210 presented a leukemic CNS
      model with leptomeningeal spread and infiltration of liver, spleen, and lymph
      nodes, whereas EHR2 cells acted as a solid tumor with no evidence of
      extracerebral disease. In all experiments, the combination of high-dose etoposide
      and ICRF-187 was significantly superior to an equitoxic dose of etoposide alone.
      Such superiority was also seen when treatment was given on days 4, 8, and 12
      after tumor inoculation. Here etoposide alone resulted in a mean increased life
      span of 12.3%, whereas the rescue regimen yielded an increase of 47% (P <
      0.0001). In conclusion, DNA topo II rescue by catalytic inhibitors is a new
      strategy enabling significant epipodophyllotoxin dose escalations; in this study,
      we have demonstrated the superiority of this strategy in two in vivo CNS tumor
      models. This concept is now being tested in a clinical trial.

PMID- 9626453
TI  - Overexpression of stromelysin-3, BM-40/SPARC, and MET genes in human esophageal
      carcinoma: implications for prognosis.
AB  - Molecular markers can improve staging and predict aggressive clinical behavior in
      esophageal cancer, thus helping to define appropriate therapeutic protocols and
      to identify patients who will benefit from surgery. We therefore characterized,
      by Northern blot and/or immunohistochemistry, the relative expression of three
      effectors involved in the invasion, angiogenesis, and dissemination of tumor
      cells in esophageal cancer versus nontumoral mucosae: (a) stromelysin-3 (ST3), a
      member of the metalloproteinase family; (b) basement membrane 40/secreted protein
      acidic and rich in cysteine (BM-40/SPARC), an extracellular matrix-associated
      protein involved in angiogenesis; and (c) the hepatocyte growth factor receptor
      MET, which triggers the scattering of epithelial cells. Results were analyzed in
      relation to clinicopathological parameters (cpTNE) including tumor size (T),
      lymph node status (N), periesophageal tissue invasion (E), disease recurrence,
      and overall survival. The ST3, BM-40/SPARC, and MET genes were found to be
      overexpressed in tumor samples compared to control mucosa. BM-40/SPARC and MET
      mRNA levels were not linked to any one of the cpTNE, indicating that this
      overexpression occurs at an early stage of neoplastic progression. In contrast,
      ST3 expression, identified by immunohistochemistry in fibroblastic cells
      surrounding neoplastic islets, correlated with tumor size and periesophageal
      tissue invasion. Of the 36 patients studied, those with high ST3 levels had
      shorter disease-free survival than those with low levels, but there was no
      relationship between the cpTNE and disease recurrence or survival. Our study
      demonstrates that ST3, BM-40/SPARC, and MET are involved in different steps of
      esophageal carcinogenesis and that ST3 overexpression is a marker of aggressive
      clinical behavior. We conclude that in esophageal cancer, ST3 might help to
      assess survival and the risk of recurrence after surgical resection.

PMID- 9626454
TI  - Epidermal growth factor receptor expression in cervical intraepithelial neoplasia
      and its modulation during an alpha-difluoromethylornithine chemoprevention trial.
AB  - Chemoprevention trials designed to prevent progression to invasive cervical
      cancer will benefit from the identification of biomarkers that assess the risk of
      developing tumors, predict likelihood of response to treatment, and measure
      biological response to intervention. The purpose of this study was to examine
      expression of epidermal growth factor receptor (EGFR) as a marker for progression
      of cervical intraepithelial neoplasia (CIN) and as a surrogate end point
      biomarker in a chemoprevention trial with alpha-difluoromethylornithine (DFMO),
      an inhibitor of ornithine decarboxylase. To evaluate quantitative and spatial
      changes in EGFR expression during cervical tumorigenesis, paraffin sections from
      42 archival cervical cone biopsies, each containing multiple stages of CIN, were
      immunohistochemically stained for EGFR, and the level and spatial expression of
      EGFR were quantitated by image analysis. In the progression from normal
      epithelium to CIN 1 to CIN 2 to CIN 3 to invasive cancer, EGFR expression showed
      two types of changes. Normal control epithelium showed EGFR expression
      predominantly confined to the basal layer, while histologically normal epithelium
      in specimens containing CIN showed relatively increased EGFR expression in the
      basal layer and the extension of EGFR expression away from the basal layer. The
      total EGFR relative staining intensity (RSI) of epithelium increased with the
      degree of CIN, predominantly due to a progressive expansion of EGFR-expressing
      cells away from the basal layer rather than an increase in the level of EGFR
      expression per cell. To determine whether EGFR expression would be modulated by a
      1-month chemopreventive intervention with DFMO, pretreatment and posttreatment
      cervical biopsy specimens from 25 patients (22 evaluable) were examined for EGFR
      expression. Although the overall levels of EGFR expression were not modulated in
      either histological responders or nonresponders, responders showed a prominent
      down-regulation of EGFR expression away from the basal layer after DFMO
      treatment. Interestingly, pretreatment EGFR expression levels predicted for DFMO
      response [i.e., eight responses (72.7%) for 11 cases with RSI levels below 0.35
      versus one response (9.1%) for 11 cases with RSI levels above 0.35 (P < 0.01)].
      These results suggest that CIN progression is associated with a spatial
      dysregulation of EGFR expression that can be reversed by DFMO treatment,
      especially in patients whose pretreatment CIN 3 lesions exhibit relatively low
      EGFR expression.

PMID- 9626455
TI  - The expression of drug resistance gene products during the progression of human
      prostate cancer.
AB  - Prostate cancer progresses from a localized disease to a widely disseminated
      malignancy. Each step along this progression pathway involves multiple genetic
      alterations that impart a survival advantage to the tumor cell over its normal
      counterparts and may confer resistance to therapy. Because metastatic prostate
      cancer is one of the most therapy-resistant human neoplasms, we studied the
      expression of certain molecular determinants of drug resistance in the context of
      tumor progression. Paraffin-embedded formalin-fixed resected prostates were
      chosen based on Gleason grade and surgical stage. Immunohistochemistry was used
      to detect the expression of multidrug resistance protein (MRP), topoisomerase II
      alpha, p53, glutathione S-transferase pi, Bcl-2, and P-glycoprotein in these
      specimens. We found that all of the proteins were expressed in resected prostate
      except for P-glycoprotein. The expression of MRP, topoisomerase II alpha, p53,
      and Bcl-2 increased with the Gleason grade. In addition, the expression of MRP,
      topoisomerase II alpha, and p53 increased with the surgical stage. In contrast,
      the glutathione S-transferase pi and Bcl-2 expression decreased with the
      increasing surgical stage. Stage was the strongest indicator of protein
      expression. These results suggest that drug resistance gene products are
      expressed in prostate cancer at the time of surgical resection. Thus, although
      the emergence of the "pan-resistance" phenotype in prostate cancer may partly be
      a function of the selection pressure exerted by therapeutic interventions,
      certain determinants of chemoresistance may be caused by genetic changes
      accompanying tumorigenesis.

PMID- 9626456
TI  - 4-(3'-Bromo-4'hydroxylphenyl)-amino-6,7-dimethoxyquinazoline: a novel quinazoline
      derivative with potent cytotoxic activity against human glioblastoma cells.
AB  - The novel quinazoline derivative 4-(3'-bromo-4'-hydroxylphenyl)-amino-6,7
      dimethoxyquinazoline (WHI-P154) exhibited significant cytotoxicity against U373
      and U87 human glioblastoma cell lines, causing apoptotic cell death at micromolar
      concentrations. The in vitro antiglioblastoma activity of WHI-P154 was amplified
      > 200-fold and rendered selective by conjugation to recombinant human epidermal
      growth factor (EGF). The EGF-P154 conjugate was able to bind to and enter target
      glioblastoma cells within 10-30 min via receptor (R)-mediated endocytosis by
      inducing internalization of the EGF-R molecules. In vitro treatment with EGF-P154
      resulted in killing of glioblastoma cells at nanomolar concentrations with an
      IC50 of 813 +/- 139 nM, whereas no cytotoxicity against EGF-R-negative leukemia
      cells was observed, even at concentrations as high as 100 microM. The in vivo
      administration of EGF-P154 resulted in delayed tumor progression and improved
      tumor-free survival in a severe combined immunodeficient mouse glioblastoma
      xenograft model. Whereas none of the control mice remained alive tumor-free
      beyond 33 days (median tumor-free survival, 19 days) and all control mice had
      tumors that rapidly progressed to reach an average size of > 500 mm3 by 58 days,
      40% of mice treated for 10 consecutive days with 1 mg/kg/day EGF-P154 remained
      alive and free of detectable tumors for more than 58 days with a median tumor
      free survival of 40 days. The tumors developing in the remaining 60% of the mice
      never reached a size > 50 mm3. Thus, targeting WHI-P154 to the EGF-R may be
      useful in the treatment of glioblastoma multiforme.

PMID- 9626457
TI  - Analysis of DNA mismatch repair proteins in human medulloblastoma.
AB  - During replication, the primary function of the eukaryotic DNA mismatch repair
      (MMR) system is to recognize and correct mismatched base pairs within the DNA
      helix. Deficiencies in MMR have been reported previously in cases of hereditary
      nonpolyposis colorectal cancer and sporadic tumors occurring in a variety of
      tissues including gliomas. Furthermore, recent evidence indicates that the MMR
      system may be involved in mediating therapeutic sensitivity to alkylating agents.
      In this study, 22 neoplastic tissue samples from 22 patients who underwent
      surgical resection for medulloblastoma, a common cerebellar tumor of childhood,
      were assayed for the presence or absence of MMR polypeptides using Western blot
      and immunohistochemical techniques. Results from these experiments indicate that
      the MMR system is not commonly deficient in medulloblastoma.

PMID- 9626458
TI  - Supersaturating infusional humanized anti-CD33 monoclonal antibody HuM195 in
      myelogenous leukemia.
AB  - Humanized anti-CD33 monoclonal antibody HuM195 specifically targets myeloid
      leukemias in vivo and has been shown to produce molecular remissions in patients
      with acute promyelocytic leukemia who are in clinical remission. Previous human
      trials have used low intermittent dosing of HuM195 at 3 mg/m2/day, which is
      adequate to saturate all available CD33 sites in vivo. In the current trial, we
      investigated supersaturating doses of HuM195. Ten patients with relapsed or
      refractory myelogenous leukemia (nine acute myelogenous leukemias and one chronic
      myelogenous leukemia) were treated on days 1-4 and 15-18 with a 4-h daily
      infusion of HuM195 at three different dose levels: 12, 24, and 36 mg/m2/day. The
      total maximum dose of HuM195 was 576 mg. The most common toxicities were grade II
      fever and rigors, seen more frequently at the highest dose. Interestingly, a
      transient and reversible drop in hemoglobin of 1-3 g/dl was seen during the
      infusion in several patients. Flow cytometric analysis showed that antigen sites
      in the peripheral blood and bone marrow (BM) remained saturated with HuM195
      during the entire 4-week trial period. At these high doses, the average plasma
      half-life of HuM195 was approximately 1 week, compared to 38 h, seen in previous
      studies. Human anti-HuM195 immune responses were not observed. One patient with
      acute myelogenous leukemia, whose disease was refractory to two rounds of
      chemotherapy, with < 10% blasts in his BM, achieved a complete remission, lasting
      > 32 months, at the first dose level. Another three patients showed a reduction
      in leukemic BM cells. These studies suggest that high doses of HuM195 achieve a
      long serum half-life, with tolerable toxicity and without immunogenicity. In
      addition, antileukemic activity was seen.

PMID- 9626459
TI  - Renal clearance, tissue distribution, and CA-125 responses in a phase I trial of
      suramin.
AB  - Suramin was administered to 49 patients in a Phase I cancer trial with real-time
      pharmacokinetic monitoring and dose individualization to achieve targeted mean
      plasma concentrations of 210 and 155 mg/liter during the 7-day period between
      days 15 and 22. Pharmacokinetic sampling after doses on days 1, 3, 5, and 8 was
      used to modify weekly suramin doses, beginning on day 15, in an attempt to
      achieve specific averaged plasma concentrations of 210 and 155 mg/liter. A 200-mg
      test dose was not effective in prospectively determining individual
      pharmacokinetic parameters and dosage requirements. Patients with peak plasma
      suramin concentrations in excess of 350 mg/liter may be more likely to experience
      neurotoxicity (P = 0.06), but there was no statistically significant effect of
      peak suramin concentration or of cumulative dose. Biopsy and autopsy tissue
      samples demonstrated low penetration of suramin into brain tissue and muscle but
      good penetration into prostate and other visceral organs. Prospective use of
      surrogate substrates for CYP1A2, CYP3A3/4, and CYP2D6 showed no consistent effect
      of suramin on these enzymes. Although a correlation between creatinine clearance
      and suramin renal clearance was found (r2 = 0.38; P < 0.00005), there was no
      correlation between creatinine clearance and total suramin clearance (P = 0.21).
      No suramin dose modification for renal or hepatic dysfunction can be supported at
      this time. Three of four ovarian cancer patients demonstrated a drop in CA-125
      serum concentrations during suramin treatment.

PMID- 9626460
TI  - Phase I study of 9-cis-retinoic acid (ALRT1057 capsules) in adults with advanced
      cancer.
AB  - 9-cis-Retinoic acid (9-cis-RA) and all-trans-RA (ATRA) are naturally occurring
      hormones. The nuclear receptors that mediate the effects of retinoids are the
      retinoic acid receptors (RARs) and the retinoid X receptors (RXRs). ATRA binds
      RAR with high affinity but does not bind to RXR, whereas 9-cis-RA, an isomer of
      ATRA, is a ligand that binds and transactivates both RARs and RXRs. The goals of
      this study were to determine the safety, tolerability, pharmacokinetics, and
      metabolic profile of 9-cis-RA in advanced cancer patients. Forty-one patients
      received oral 9-cis-RA (ALRT1057; Panretin capsules) at doses ranging from 5-140
      mg/m2/day. Twenty-six patients were treated once daily with up to 140 mg/m2; a
      subsequent cohort of 15 patients were treated twice daily (b.i.d.) at 100-140
      mg/m2/day (50, 60, and 70 mg/m2 b.i.d.) to evaluate a b.i.d. dosing regimen.
      Headache was the most frequent adverse event and was dose limiting in 3 of 41
      patients. Skin toxicity was the next most common toxicity and was seen in 11 of
      41 patients; it was typically mild and limited to skin dryness and erythema.
      Other toxicities included conjunctivitis, flushing, diarrhea, transaminitis,
      hypercalcemia, and asymptomatic hypertryglyceridemia. Toxicities were typically
      dose related, occurred primarily above 83 mg/m2/day, and were not ameliorated by
      b.i.d. dosing. No tumor responses were observed. The mean day 1 area under the
      plasma concentration-time curve and peak plasma concentration values were dose
      proportional over all dose levels, whereas day 15 area under the plasma
      concentration-time curve and peak plasma concentration values were nonlinear
      above 83 mg/m2/day, suggesting that 9-cis-RA induced its own metabolism at doses
      equal to and above 140 mg/m2/day. 9-cis-RA is a retinoid receptor pan agonist
      with a more favorable pharmacokinetic and toxicity profile than that observed
      with previously studied retinoids and merits further investigation.

PMID- 9626461
TI  - Dose escalation of the hypoxic cell sensitizer etanidazole combined with
      ifosfamide, carboplatin, etoposide, and autologous hematopoietic stem cell
      support.
AB  - Multiple mechanisms of drug resistance contribute to treatment failure. Although
      high-dose therapy attempts to overwhelm these defenses pharmacologically, this
      approach is only successful in a fraction of treated patients. Many drug
      resistance mechanisms are shared between malignant and normal cells, but the
      expression of various drug resistance mechanisms associated with hypoxia is
      largely confined to tumor tissue. Thus, reversal of this mechanism is likely to
      provide a therapeutic advantage to the host. This study was designed to define
      the dose-limiting toxicities and maximum tolerated dose of etanidazole when it is
      given concurrently with high-dose ifosfamide, carboplatin, and etoposide (ICE),
      with hematopoietic stem cell support. The maximum tolerated doses of high-dose
      ICE were administered concurrently with dose escalations of etanidazole, a
      hypoxic cell sensitizer. All agents were given by 96-h continuous i.v. infusion
      beginning on day -7. Mesna uroprotection was provided. Autologous marrow and
      cytokine mobilized peripheral blood progenitor cells were reinfused on day 0.
      Granulocyte colony-stimulating factor was administered following reinfusion until
      the granulocytes recovered to > 1000/microliter. Fifty-five adults with advanced
      malignancies were enrolled in cohorts of five to nine patients. Four dose levels
      of etanidazole between 3 and 5.5 g/m2/day (12, 16, 20, and 22 g/m2 total doses)
      and two doses of carboplatin (1600 and 1800 mg/m2 total doses) were evaluated.
      Seven patients died of organ toxicity (13%); two each from veno-occlusive disease
      of liver and sepsis; and one each from sudden death, renal failure, and
      refractory thrombocytopenic hemorrhage. Five deaths occurred at the top dose
      level. One additional patient suffered a witnessed cardiorespiratory arrest from
      ventricular fibrillation and was resuscitated. Dose-dependent and largely
      reversible peripheral neuropathy was observed consisting of two syndromes: severe
      cramping myalgic/neuralgic pain, predominantly in stocking glove distribution,
      occurring between day -3 and day 0, and a sensory peripheral neuropathy with
      similar distribution peaking around day +60. The maximal achievable dose of
      etanidazole (16 g/m2 dose level) resulted in a mean serum level of 38
      micrograms/ml (25-55 micrograms/ml). Etanidazole significantly enhanced host
      toxicity of high-dose ICE. Effective modulatory doses of etanidazole could not be
      given with acceptable toxicity using this schedule.

PMID- 9626462
TI  - Phase II study of dexverapamil plus anthracycline in patients with metastatic
      breast cancer who have progressed on the same anthracycline regimen.
AB  - The purpose of this study is to evaluate whether metastatic breast cancer that
      has progressed on an anthracycline-containing drug regimen will subsequently
      respond to that identical regimen if dexverapamil, a modulator of P-glycoprotein
      mediated drug resistance, is given concomitantly. Eligible patients received 180
      mg/m2 dexverapamil every 6 h for 15 doses with the anthracycline administered 30
      min after the seventh dose. Blood for dexverapamil levels was drawn before and 30
      min after this dose. When possible, biopsies were obtained to measure mdr-1
      expression by reverse transcription-PCR and by image cytometry. Of the 21
      patients entered onto the trial, 20 were evaluable for response. There were two
      partial responses (10%) that both lasted for 6 months, and two additional
      patients had stable disease. Seven patients had asymptomatic cardiotoxicity
      consisting of hypotension (24%), bradycardia (5%), or prolongation of the P-R
      interval (14%). Two patients developed acute congestive heart failure, one on
      dexverapamil and one 10 days after stopping it. Dexverapamil did not seem to
      increase anthracycline toxicity. The median trough dexverapamil plus norverapamil
      level on day 3 was 1110 ng/ml (range, 186-3385 ng/ml), and the median peak level
      was 2164 ng/ml (range, 964-8382 ng/ml). There was poor correlation between
      reverse transcription-PCR and image cytometry for the level of mdr-1 expression.
      Because dexverapamil has been shown to affect doxorubicin pharmacokinetics
      subsequent to the initiation of this trial, it cannot be concluded that the
      responses seen were necessarily due to P-glycoprotein inhibition. Additional
      studies are necessary to determine whether mdr-1 modulators can reverse clinical
      drug resistance in breast cancer patients. The intrinsic cardiotoxicity of
      dexverapamil makes it less suitable for such studies than several other available
      agents.

PMID- 9626463
TI  - A phase I and translational study of sequential administration of the
      topoisomerase I and II inhibitors topotecan and etoposide.
AB  - Because topoisomerase (topo) I- and topo II-targeting agents exert their
      principal effects on the two major classes of enzymes involved in regulating DNA
      topology in the cell, there has been considerable interest in evaluating
      combinations of these classes of agents. In preclinical studies of inhibitors of
      topo I and topo II in combination, drug scheduling and sequencing have been
      critical determinants of antitumor activity, with a greater magnitude of
      cytotoxicity generally occurring when treatment with the topo I inhibitor
      precedes treatment with the topo II-targeting agent. The underlying mechanism
      that has been proposed to explain this schedule dependency is compensatory up
      regulation of topo II and, therefore, enhanced cytotoxicity of topo II inhibitors
      in cells treated initially with topo I inhibitors. The feasibility of
      sequentially administering the topo I inhibitor topotecan (TPT) followed by the
      topo II inhibitor etoposide to patients with advanced solid malignancies was
      evaluated in this Phase I and translational laboratory study. Fifty patients with
      solid neoplasms were treated with TPT doses ranging from 0.17 to 1.05 mg/m2/day
      as a 72-h continuous (i.v.) infusion on days 1-3 followed by etoposide, 75 or 100
      mg/m2/day as a 2-h i.v. infusion daily on days 8-10. The combined rate of severe
      neutropenia and thrombocytopenia was unacceptably high above the TPT
      (mg/m2/day)/etoposide (mg/m2/day) dose levels of 0.68/100 and 0.68/75 in
      minimally and heavily pretreated patients, respectively, and these dose levels
      are recommended for further disease-directed evaluations of TPT/etoposide on this
      administration schedule. Successive biopsies of accessible tumors were obtained
      for quantitation of topo I and II levels prior to and immediately after treatment
      with TPT and prior to and immediately after treatment with etoposide in seven
      patients. The results of these limited studies in tumors did not fully support
      the proposed mechanistic rationale favoring the development of this particular
      sequential TPT/etoposide regimen, because only two of the six patients' tumors in
      whom topo I was successively measured had either modest or substantial decrements
      in topo I levels following treatment with TPT, and the principal effect of
      interest, up-regulation of topo II following treatment with TPT, was clearly
      documented in the tumors of only one of six subjects in whom successive
      measurements of topo I were performed. Even in view of the notable objective
      antitumor activity in three subjects, including a complete response in a patient
      with colorectal carcinoma and partial responses in one patient each with non
      small cell lung and gastric carcinomas, the toxicity and ancillary laboratory
      results do not provide substantial evidence that sequential treatment with TPT
      and etoposide might be more advantageous than either TPT or etoposide
      administered as a single agent.

PMID- 9626464
TI  - Biological markers as a predictor for response and prognosis of unresectable
      gastric cancer patients treated with 5-fluorouracil and cis-platinum.
AB  - We investigated the utility of examining biological markers to predict
      chemoresponse and survival. The subjects consisted of 39 unresectable gastric
      cancer patients treated with a combination of 5-fluorouracil and cis-platinum.
      The expression of p53, bcl-2, thymidylate synthase (TS), glutathione S
      transferase pi (GST-pi), and vascular endothelial growth factor (VEGF) in the
      formalin-fixed biopsy samples of primary tumors before chemotherapy was examined
      immunohistochemically. The positive rate for VEGF, bcl-2, TS, p53, and GST-pi was
      51, 10, 46, 38, and 69%, respectively. VEGF-positive cases showed a higher
      response rate than did negative cases (11 of 20 versus 2 of 19 cases; P =
      0.0057). The cases that were negative for p53, TS, bcl-2, and GST-pi were more
      likely to respond to chemotherapy than the cases that were positive for these
      markers. The 10 cases having 4 or 5 favorable phenotypes (VEGF positive, p53
      negative, bcl-2 negative, TS negative, and GST-pi negative) survived longer than
      the remaining 29 cases (P = 0.0069). Multivariate analysis revealed that the
      number of favorable phenotypes (> or = 4 versus < or = 3) had a greater impact on
      survival than performance status (0 versus 1 or 2), age (> 60 years versus < or =
      60 years), macroscopic type (scirrhous versus nonscirrhous), histological type
      (intestinal versus diffuse), or tumor extent (locally advanced versus
      metastatic). Immunohistochemical examination of biological markers in biopsy
      samples may be useful in predicting the clinical outcome of unresectable gastric
      cancer patients treated with 5-fluorouracil and cis-platinum.

PMID- 9626465
TI  - Assessment of the biological malignancy of hepatocellular carcinoma: relationship
      to clinicopathological factors and prognosis.
AB  - It is difficult to determine the prognosis of patients with hepatocellular
      carcinoma (HCC). Assessment of the clinicopathological and biological malignancy
      of HCC may help in determining treatment strategies and predicting outcome. The
      tumor DNA content, p53 protein expression, proliferating cell nuclear antigen
      labeling index, and argyrophilic proteins of nuclear organizer regions were used
      as markers of biological malignancy. A correlation between these biological
      parameters and clinicopathological factors was sought. DNA aneuploidy was
      observed in 31 of 80 tumors (38.8%). Aneuploidy increased as differentiation
      decreased. The overall survival rate of patients with aneuploid tumors was
      significantly poorer than that of patients with diploid tumors. p53
      overexpression was observed in 18 of 80 tumors (22.5%). The incidence of p53
      positivity increased significantly with increasing tumor size and poorer
      differentiation. The overall survival rate of p53-positive patients was
      significantly worse than that of p53-negative patients. The proliferating cell
      nuclear antigen labeling index and the mean number of argyrophilic proteins of
      nuclear organizer regions were higher in more poorly differentiated lesions. We
      conclude that DNA ploidy and p53 expression are useful prognostic indicators in
      HCC. Cell proliferation increases as HCC progresses. With progression, tumors
      tend to become more poorly differentiated.

PMID- 9626466
TI  - Tumor angiogenesis and vascular endothelial growth factor expression in stage I
      lung adenocarcinoma.
AB  - Vascular endothelial growth factor (VEGF) is one of the most important factors
      for angiogenesis in various malignant tumors. However, the biological
      significance of VEGF in lung adenocarcinoma remains unclear. We stained
      intratumoral microvessels immunohistochemically using anti-CD34 antibody and
      analyzed VEGF expression using anti-VEGF antibody in 44 cases of stage I lung
      adenocarcinoma. Of the 44 patients studied, 14 patients had a postoperative
      relapse, and 30 patients did not. The mean microvessel count (MVC) in stage I
      lung adenocarcinoma was 79.5 +/- 26.9 per x200 microscopic field.
      Immunohistochemical expression of VEGF was found in 27 of 44 cases of stage I
      lung adenocarcinoma. The mean MVC in cases of VEGF-positive lung adenocarcinoma
      (86.4 +/- 28.2) was significantly higher than that in cases of VEGF-negative lung
      adenocarcinoma (68.6 +/- 21.4; P < 0.05). The high-MVC group patients (MVC > 80)
      had significantly worse survival rates than those in the low-MVC group (MVC < or
      = 80; P < 0.01), and patients with VEGF-negative tumors had significantly better
      survival rates than those with VEGF-positive tumors (P < 0.05). We conclude that
      angiogenesis, as assessed by intratumoral MVCs, is a significant prognostic
      factor in stage I lung adenocarcinoma, and that VEGF is an important angiogenic
      factor in stage I lung adenocarcinoma.

PMID- 9626467
TI  - Prognostic value of prostate-specific antigen for women with breast cancer: a
      large United States cohort study.
AB  - Prostate-specific antigen (PSA) is a valuable tumor marker used for diagnosis and
      management of prostate cancer. Recently, PSA has been found in various female
      tissues and body fluids. Female breasts, both normal and abnormal, including
      cancerous tissues, can produce PSA, and this production is regulated by androgens
      and progestins. Preliminary data suggested that patients with breast tumors
      positive for PSA may have better prognosis compared to those with PSA-negative
      breast tumors. This study examines the prognostic value of PSA in a large cohort
      study of United States patients. Using a PSA assay that has a lower detection
      limit of 0.001 ng/ml, we measured PSA in tumor cytosolic extracts of 953 women
      with primary breast cancer. Other information available for this study included
      age, follow-up time, survival outcome, tumor size, nodal status, steroid hormone
      receptor levels, DNA analysis by flow cytometry, and postoperative treatment. The
      median follow-up time was 73 months. During the follow-up, 200 patients relapsed
      and 188 died. PSA presence was found to be significantly associated with smaller
      tumors, tumors with low S-phase fraction, diploid tumors, younger patient age,
      and tumors with lower cellularity. Survival analysis indicated that the relative
      risks (RRs) for relapse and death were both significantly lower [RR = 0.67 (P =
      0.01) for relapse; RR = 0.72 (P = 0.05) for death] in PSA-positive patients
      (levels higher than the 30th percentile of PSA values) than in PSA-negative
      patients. The reduced risks for relapse and death remained statistically
      significant after other clinical and pathological variables were adjusted in the
      multivariate analysis [RR = 0.68 (P = 0.02) for relapse; RR = 0.65 (P = 0.02) for
      death]. Our results suggest that the measurement of PSA in breast tumor extracts
      provides additional information on the prognosis of patients with primary breast
      cancer.

PMID- 9626468
TI  - p21waf1/cip1 and transforming growth factor beta 1 protein expression correlate
      with survival in non-small cell lung cancer.
AB  - p21waf1/cip1 encodes a cyclin-dependent kinase inhibitor that is
      transcriptionally activated by the p53 tumor suppressor gene, transforming growth
      factor beta 1 (TGF-beta 1), AP2, and other pathways. Because p21waf1/cip1, p53,
      and TGF-beta 1 all regulate apoptosis and the cell cycle, we tested the
      hypothesis that their relative protein levels would correlate with biological
      features including the survival of non-small cell lung cancer (NSCLC) patients.
      We conducted an immunohistochemical analysis of p21waf1/cip1 and TGF-beta 1 and
      identified four patient groups with distinct survival outcomes. Concordant
      p21waf1/cip1 and TGF-beta 1 expression (i.e., either high p21waf1/cip1 and high
      TGF-beta 1 expression or low p21waf1/cip1 and low TGF-beta 1 expression)
      predicted 70% disease-free survival at 2000 days of follow-up. Discordant
      p21waf1/cip1 and TGF-beta 1 expression (i.e., either high p21waf1/cip1 and low
      TGF-beta 1 expression or low p21waf1/cip1 and high TGF-beta 1 expression)
      predicted 35% disease-free survival (P = 0.0003; log-rank test). These survival
      relationships were not attributable to differences in grade, stage, or p53
      status. Although current models do not fully explain these complex interactions,
      most of these data fit a paradigm whereby TGF-beta 1 regulation determines NSCLC
      survival. In addition to the survival correlation, we found that high
      p21waf1/cip1 protein expression correlated with high tumor grade (P = 0.014).
      There is little evidence that p21waf1/cip1 protein levels accurately predict p53
      mutation status in NSCLC; specifically, 20 of 48 (42%) tumors with p53 mutations
      contained high levels of p21waf1/cip1 protein. These findings indicate that
      p21waf1/cip1 immunohistochemical analysis may provide useful information
      concerning the biological properties of NSCLC.

PMID- 9626469
TI  - Motility related protein 1 (MRP1/CD9) expression in colon cancer.
AB  - It is important to detect genes that may be good prognostic markers for colon
      cancer patients. With this in mind, we identified the motility related protein-1
      (MRP1/CD9) gene in human colon tissues. The aim of this study was to clarify the
      significance of MRP1/CD9 gene expression in human colon cancers. We performed the
      differential mRNA display technique between tumor/normal paired samples of the
      colon and identified MRP1/CD9. Eighty-two surgical specimens of primary
      colorectal cancer were analyzed by means of reverse transcription-PCR for the
      MRP1/CD9 gene. Its expression status and clinicopathological variables were
      analyzed univariately and multivariately. The MRP1/ CD9 mRNA expression was
      positive in 56 cases and negative in 26 cases. The MRP1/CD9 negative cases showed
      a significantly higher frequency of venous-vessel invasion and liver metastasis,
      or a worse prognosis than the MRP1/CD9 positive cases (P < 0.05). Multivariate
      analysis with the Cox regression model disclosed that MRP1/CD9 expression was an
      independent prognostic factor distinct from the lymph node status. The findings
      imply that the study of MRP1/CD9 expression may be useful for predicting
      prognosis of patients with colorectal cancer.

PMID- 9626470
TI  - Prognostic values of cathepsin B and carcinoembryonic antigen in sera of patients
      with colorectal cancer.
AB  - The level of cathepsin B (Cat B) was determined in sera obtained preoperatively
      from 325 patients with colorectal cancer using an ELISA. Control sera from 90
      healthy blood donors were analyzed. The levels of Cat B detected included all
      forms that were present in the sera, i.e., mature enzyme, precursor molecule, and
      enzyme-inhibitor complexes. The level of Cat B was significantly increased in
      sera of patients with colorectal cancer. The median level was 10.7 ng/ml versus
      2.1 ng/ml in controls (P < 0.0001). A correlation between Cat B serum level and
      advanced Dukes' stage (P < 0.003) was found, whereas no associations have been
      found with age, sex, or level of carcinoembryonic antigen (CEA). In survival
      analysis, the patients with high serum Cat B experienced significantly lower
      survival probability. At the optimal cutoff value of 9.4 ng/ml, the relative
      hazard ratio was 1.8 (95% confidence interval, 1.1-2.8; P = 0.016) in the
      univariate Cox proportional hazards model. The median observation time was 4.4
      years (range, 3.2-5.5 years). In multivariate analysis, Dukes' stage was the
      strongest prognostic variable, followed by age, whereas serum Cat B and CEA were
      not significant prognostic factors in this model, in accordance with their
      association with Dukes' stage. When the data for Cat B and CEA were combined, CEA
      positive patients were further separated by Cat B into high- and low-risk groups.
      Patients with high serum levels of both molecules had significantly shorter
      survival (relative hazard ratio of 2.2; 95% confidence interval, 1.5-3.2; P <
      0.0001), as compared with patients with low levels of both molecules.

PMID- 9626471
TI  - Tumor-associated antigen 22-1-1 expression in the uterine cervical squamous
      neoplasias.
AB  - We have reported that a novel tumor-associated antigen (Ag), 22-1-1, was
      expressed in cancer cells derived mainly from the uterus and ovary [K. Sonoda et
      al., Cancer (Phila.), 77: 1501-1509, 1996]. The 22-1-1 Ag existed not only in
      adenocarcinomas but also in squamous cell carcinomas in the uterine cervix. Here,
      a relationship between tumor progression and invasion and 22-1-1 Ag expression
      was investigated in squamous cell neoplasms of the uterine cervix using
      immunohistochemical staining. The 22-1-1 Ag was not detected in normal uterine
      cervix (0 of 10 total cases) and dysplasias (0 of 47 total cases). However, 20%
      of carcinoma in situ (4 of 20 total cases) and 16.7% of microinvasive carcinomas
      (2 of 12 total cases) stained positively for 22-1-1 Ag. Moreover, areas depicting
      microinvasion on histology in uterine cancers (stage Ia) were more strongly
      stained than carcinoma in situ lesions. 22-1-1 Ag expression was found to be more
      frequent in invasive squamous cell carcinomas (82.6%; 57 of 69 total cases). The
      22-1-1 Ag existed both in the cytoplasm and on the membrane of cancer cells.
      These findings suggest that 22-1-1 Ag expression might be related to tumor cell
      progression and invasion in the uterine cervical squamous cell epithelium.

PMID- 9626472
TI  - CD28, a marker associated with tumoral expansion in multiple myeloma.
AB  - CD28 expression was thoroughly investigated on plasma cells of monoclonal
      gammopathy of undetermined significance, multiple myeloma (MM), and human myeloma
      cell lines. CD28+ plasma cells were detected in 19% of 31 monoclonal gammopathy
      of undetermined significance, 41% of 116 MM, and 100% of 13 human myeloma cell
      lines. CD28+ myeloma cells were detected in 21 of 79 (26%) MM cases at diagnosis,
      13 of 22 (59%) at medullary relapse (P < 0.009), and 14 of 15 (93%) at
      extramedullary relapse (P = 0.05), including 10 of 10 (100%) secondary plasma
      cell leukemias (P = 0.05). Serial studies in individual patients confirmed the
      emergence of CD28+ myeloma cells with tumoral expansion and treatment failure.
      This was significantly correlated with the expression of CD28 ligand, i.e., CD86
      (but not CD80), and with an increase in the proliferative activity (labeling
      index) of myeloma cells in bone marrow. Whereas the expression of CD56 defines a
      particular subset of myeloma patients, CD28 is the only antigen for which
      expression correlates with tumor progression. Our data show that an aggressive
      compartment of CD28+ and CD86+ myeloma cells emerges during the course of MM in
      vivo, indicating that CD28 could be aberrantly expressed on highly malignant
      (possibly mutated) myeloma cells. Conversely, a subset of proliferative
      plasmablasts coexpressing CD28 and CD86 could be the normal counterpart of the
      clonogenic myeloma stem cell because a subset of CD28+ plasma cells was observed
      in 6 of 6 cases of reactive plasmocytosis.

PMID- 9626473
TI  - Detection of K-ras gene mutations in plasma DNA of patients with pancreatic
      adenocarcinoma: correlation with clinicopathological features.
AB  - We investigated the presence of K-ras gene mutation in plasma DNA and assessed
      its clinical value in patients with pancreatic adenocarcinoma. Mutations in codon
      12 of the K-ras gene were examined by mutant allele-specific amplification method
      using DNA extracted from surgical specimens and plasma samples of 21 patients
      with pancreatic adenocarcinoma. K-ras gene mutation was detected in 15 of 21
      (71%) primary tumors. In 9 of 15 (60%) patients with K-ras gene mutation-positive
      tumors, an identical mutation was detected in the plasma DNA. None of four
      patients with chronic pancreatitis or five healthy subjects had such mutations in
      plasma DNA. Tumors positive for K-ras gene mutation in plasma DNA were
      significantly larger (P = 0.04) and less likely to result in a curative cure
      after surgical resection (P = 0.09) than those negative for the mutation. Other
      clinicopathological features, including age, sex, histological type, mode of
      invasion, and metastasis, did not correlate with K-ras gene mutations in plasma
      DNA. Treatment resulted in disappearance of K-ras gene mutations in plasma DNA in
      six of nine (67%) patients. Three patients with a persistently positive K-ras
      gene mutation in pre- and post-treatment plasma samples were likely to show early
      recurrence or have a progressive disease. Our findings suggest that K-ras gene
      mutation can be detected in plasma DNA of patients with pancreatic
      adenocarcinoma. Detection of K-ras mutations in plasma may be clinically useful
      for evaluating tumor burden and efficacy of treatment.

PMID- 9626474
TI  - Quantitative reverse transcriptase-polymerase chain reaction measured expression
      of MDR1 and MRP in primary breast carcinoma.
AB  - To evaluate the clinical significance of drug resistance mechanisms in breast
      cancer, we examined the expression of MDR1 and MRP in primary breast carcinoma
      and normal adjacent tissue using a highly quantitative and reproducible reverse
      transcription-PCR assay. Expression of both genes was observed in all specimens
      examined, both tumor (n = 74) and normal adjacent tissue (n = 55). The expression
      of MDR1, however, was low, with the level of expression being 25 times less than
      the drug-resistant control cell line KB 8-5. Immunohistochemical analysis of P
      glycoprotein corroborated the PCR results; only 6% (2 of 31) were positive for
      JSB1 staining, and 0 of 32 were positive for for UIC2. MRP expression did not
      exceed control cell line levels, and immunohistochemistry detected moderate
      levels of expression. MDR1 expression was independent of grade, stage, tumor
      size, nodal status, metastasis, and estrogen receptor and progesterone receptor
      status. There was, however, a significant correlation of MDR1 expression with age
      and histology. Approximately twice the expression of MDR1 was observed in the <
      50 age group compared to the > 50 age group, and lobular carcinoma had 4 times
      the expression of MDR1 of other histological types. MRP expression was
      independent of all other clinical parameters. Thus, these results show that
      although MDR1 expression is detectable in primary breast carcinoma by PCR, this
      expression as measured by quantitative reverse transcriptase-PCR is extremely
      low. The significance of these low levels is yet to be determined. MDR1
      expression was higher in < 50 age group and lobular carcinoma, which may
      contribute to poor prognosis associated with young age and lobular histology.

PMID- 9626475
TI  - Flow cytometric DNA analyses of benign breast lesions detected by screening
      mammography.
AB  - There is little information regarding flow cytometric DNA analyses of benign
      breast lesions. This prospective study consists of mammographic and pathological
      correlation of DNA flow cytometric analyses of specimen mammography-guided fine
      needle aspirates (FNAs) of 189 consecutive benign breast lesions and 114 FNAs of
      adjacent normal tissue as a control. Clinical follow-up was also performed.
      Aneuploidy was detected in 14 of 189 (7%) benign lesion specimen mammography
      guided FNAs and in only 1 of 114 (0.9%) FNAs of adjacent normal tissue (P =
      0.01). Aneuploidy was detected in two (33%) benign intramammary lymph nodes
      compared with four (12%) benign lesions with atypia, one benign lesion (3%) with
      hyperplasia, four benign lesions (10%) with adenosis, and three (4%) other benign
      lesions (P = 0.01). There were no significant associations between DNA content
      and S-phase percentage and patient age, mammographic appearance, or extent.
      During a median follow-up of 40 months (range, 6-84 months), 2 of 13 (15%)
      patients with aneuploid benign lesions developed ipsilateral breast carcinoma
      compared with 5 of 175 (3%) patients with diploid benign lesions (odds ratio,
      6.18; 95% confidence interval, 1.08-35.56). Our data suggest that aneuploidy,
      which is detected in a variety of benign breast lesions, may be associated with a
      higher risk of development of breast carcinoma. The combined techniques of
      specimen mammography-guided fine-needle aspiration and flow cytometry provide a
      practical translational research method for the study of benign breast disease.

PMID- 9626476
TI  - Differential permeability of a human brain tumor xenograft in the nude rat:
      impact of tumor size and method of administration on optimizing delivery of
      biologically diverse agents.
AB  - To assess how to maximize drug delivery to intracerebral tumors and surrounding
      brain, this study examined the effects of route and method of administration and
      tumor size on the distribution of three agents in a nude rat intracerebral tumor
      xenograft model. Aminoisobutyric acid (M(r) 103), methotrexate (M(r) 454), and
      dextran 70 (M(r) 70,000) were administered i.v. or intra-arterially (i.a.) with
      or without osmotic blood-brain barrier disruption (BBBD) at 8, 12, or 16 days
      after tumor cell inoculation (n = 72). A 2.2- to 2.5-fold increase in delivery to
      tumor and surrounding brain was observed when i.a. was compared with i.v., and a
      2.5- to 7.6-fold increase was observed when BBBD was compared with the saline
      control. The combined effect of i.a. administration and BBBD was to increase
      delivery 6.3-16.7-fold. The greatest benefit of BBBD was seen in animals with 8
      day tumors, whereas BBBD had less benefit in improving delivery to intracerebral
      tumor and brain around tumor as the tumors grew larger. Regional delivery
      decreased as the molecular weight of the agent increased. Based on these results,
      we suggest that i.a. administration of antitumor agents may be adequate to obtain
      initial responses in large, very permeable, intracerebral tumors. However, in
      smaller, less permeable tumors or after an initial response to treatment, there
      may be a significant therapeutic advantage to i.a. agent administration and BBBD.

PMID- 9626477
TI  - The growth inhibitory effect of N1,N12-bis(ethyl)spermine in small cell lung
      cancer cells is maintained in cells expressing the c-myc and Ha-ras oncogenes.
AB  - The N',N"-bis(ethyl) polyamine analogues demonstrate great potential as
      chemotherapeutic agents for lung cancer. This study examines how the expression
      of two oncogenes frequently associated with a worsened prognosis in lung cancer,
      c-myc and mutated ras, as well as the phenotypic transition induced by these
      genes, affects the sensitivity of small cell lung cancer (SCLC) cells to these
      polyamine analogues. Treatment with N1,N12-bis(ethyl)spermine (BE-Spm), a
      representative analogue, depresses polyamine levels and is cytostatic for the NCI
      H209 classic SCLC cell line. Both the overexpression of c-myc and the expression
      of oncogenic v-Ha-ras in these cells produce phenotypes that retain sensitivity
      to this growth inhibition. This sensitivity to BESpm is mediated by distinct
      pathways in these oncogene-expressing cells. c-myc overexpression markedly
      increases the expression of ornithine decarboxylase, which is then down-regulated
      by BESpm. In contrast, v-Ha-ras expression highly induces the polyamine catabolic
      enzyme spermidine/spermine N1-acetyltransferase. These findings suggest that the
      bis(ethyl)polyamine compounds may have broad utility for the treatment of both
      SCLC and non-SCLC, including those expressing oncogenic c-myc and ras.

PMID- 9626478
TI  - Potential interactions between antitubulin agents and temperature: implications
      for modulation of multidrug resistance.
AB  - We analyzed the effect of high temperature (a 1-h incubation at 43 degrees C) on
      the accumulation and cytotoxicity of vinblastine and docetaxel in two model cell
      lines, K562 and MESSA, and their multidrug resistance (MDR) counterparts, K562/R7
      and MESSA/Dx5. High temperature increased the amount of intracellular vinblastine
      and docetaxel significantly in MESSA cell and, to a much lesser extent, in K562
      cells. MDR-positive cells retained a profound drug accumulation defect at 43
      degrees C. Hyperthermia enhanced the cytotoxic effect of vinblastine (but not
      docetaxel) in both K562 and MESSA cells, but not in the MDR-positive variants.
      PSC833, a potent modulator of P-glycoprotein, induced high levels of drug
      accumulation in the two MDR-positive cell lines at both 37 degrees C and at 43
      degrees C. PSC833 also significantly reduced the resistance levels of the two MDR
      positive lines at both 37 degrees C and at 43 degrees C. The effect of
      hyperthermia on drug accumulation thus seems to depend on the cell line, whereas
      the effect on cytotoxicity depends on the type of compound. The MDR phenotype
      remains a therapeutic obstacle at 43 degrees C but is accessible to modulation.

PMID- 9626479
TI  - Efficacy of pyridoxine to ameliorate the cutaneous toxicity associated with
      doxorubicin containing pegylated (Stealth) liposomes: a randomized, double-blind
      clinical trial using a canine model.
AB  - A cutaneous reaction termed palmar-plantar erythrodysesthesia (PPES) or hand-foot
      syndrome can be dose limiting for Doxil, a doxorubicin containing pegylated
      (Stealth) liposome. The objective of this study was to determine the ability of
      concomitant pyridoxine therapy to prevent the development of PPES during Doxil
      therapy. Forty-one dogs with non-Hodgkin's lymphoma were randomized in a double
      blind fashion to receive either oral pyridoxine or placebo daily during Doxil
      chemotherapy (1.0 mg/kg, i.v., every 3 weeks for a total of five treatments).
      Cutaneous toxicity was determined by clinical and histological scoring. No
      difference was observed in remission rates (71.4 versus 75%) achieved between
      groups. The likelihood of developing serious PPES and having to decrease or
      discontinue Doxil therapy was 4.2 times (relative risk) greater in placebo group
      dogs than in pyridoxine group dogs (P = 0.032). Pyridoxine did not completely
      abrogate PPES; however, it occurred later and less dramatically than in placebo
      treated dogs and resulted in fewer treatment delays or discontinuations, allowing
      a higher cumulative dose of Doxil to be received. Compared to the 5.0 mg/kg
      cumulative target dose, pyridoxine-treated dogs received a median cumulative dose
      of 4.7 mg/kg (mean, 4.1 mg/kg), and the placebo-treated dogs received a median of
      2.75 mg/kg (mean, 2.9 mg/kg; P < 0.028). A trend (P = 0.084) toward prolongation
      of remission length was observed in dogs receiving pyridoxine, which was likely
      attributable to their ability to receive more Doxil without delay or
      discontinuation. We conclude that pyridoxine is effective in delaying the onset
      and severity of PPES in this canine model.

PMID- 9626480
TI  - Telomerase activity of sarcoma cell lines and fibroblasts is independent of p53
      status.
AB  - Telomerase activity is necessary for the stabilization of telomeres, which
      function to overcome cellular senescence and are linked to unlimited cell
      proliferation. Activation of telomerase is characteristic of immortalized cell
      lines and most tumors. The p53 gene has been implicated as a crucial barrier to
      unlimited cell proliferation, and its absence has been shown to allow direct
      immortalization of cells by certain oncogenes. The p53 gene may have an
      additional function of signaling cell growth arrest in response to telomere
      shortening, which occurs with repeated cellular divisions and ultimately
      threatens chromosomal stability. This prompted us to consider whether the enzyme
      telomerase, responsible for adding new telomeres to chromosomal ends, may be
      affected by the p53 status of normal and malignant cells. We investigated whether
      a relationship between telomerase and p53 could be demonstrated in a human
      sarcoma cell line containing a missense p53 mutation and several stable
      transfectants that express the wild-type p53 gene or a temperature-sensitive
      mutant of p53. All cell lines had readily detectable telomerase activity
      regardless of p53 status. In addition, murine fibroblast cell strains established
      from tissues of p53+/+ and p53-/- (p53 knockout) mice expressed telomerase
      regardless of the p53 status of their tissue of origin. Levels of telomerase
      subunit mRNA (hEST2) were comparable among cell lines and tissues with different
      p53 status. These results imply that p53 status is not associated with telomerase
      activity per se and that activation of telomerase can occur either in cells
      completely devoid of p53 or in cells that have functional p53.

PMID- 9626481
TI  - Contraception in women with special medical needs.
AB  - Over 10% of women of reproductive age have experienced a serious chronic physical
      disorder. Reproductive health issues including contraception are frequently
      ignored in these individuals. Clinicians should have available current knowledge
      regarding interactions between contraception and these conditions.

PMID- 9626482
TI  - Avascular necrosis.
AB  - There are multiple conditions associated with the development of osteonecrosis
      including trauma, hemoglobinopathies, Caisson disease, local infiltrative
      lesions, hypercortisolism, alcohol consumption, chronic renal failure, and
      autoimmune disease.

PMID- 9626483
TI  - The female athlete.
AB  - Although there are many similarities between men and women involved in sport
      activities, certain issues are unique to the female athlete. This article
      presents and brings to light some of the more important concerns that are
      specific to women engaged in sports.

PMID- 9626484
TI  - Psychological stress, emotional behavior & coronary heart disease.
AB  - Psychological stress and chronic anxious behavior have a tremendous impact on our
      heart and biological rhythm of the body. Both are responsible for new development
      or promotion of coronary heart disease and may be associated with unpredictable
      adverse coronary events.

PMID- 9626485
TI  - New technology allows physicians to cleanse "bad" cholesterol from patient's
      blood without removing healthy elements.

PMID- 9626486
TI  - Prostate cancer switch may yield map of cancer machinery, targets for drugs.

PMID- 9626487
TI  - Butyric acid from the diet: actions at the level of gene expression.
AB  - A number of components present in the diet, although nutritionally nonessential,
      have been discovered to have beneficial effects toward both general health and
      disease prevention/protection. One such nutrient, butyric acid, can be derived in
      large quantities from bacterial fementation of dietary fiber in the bowel and is
      also a component of bovine milk. In gut fermentation, the production of butyric
      acid defines its delivery point; thus, the synthesis and site of action of
      butyric acid are in close proximity and have frustrated the investigation of its
      activities in vivo. Recent research has, however, revealed a number of activities
      of butyric acid toward isolated cells. In particular, its ability to modify
      nuclear architecture and induce death by apoptosis in colon cancer cells is
      arousing great interest. Butyric acid changes the structure of chromatin through
      its effects on posttranslational modifications, key modifications being
      acetylation and phosphorylation of the nuclear histones. Butyric acid can also
      modify the differentiation state of cells, and in the case of cancerous colonic
      cells overcomes their resistance to normal programmed death. Thus, the activities
      of this fermentation product of dietary fiber may contribute substantially to the
      decreased incidence of bowel cancer that has been associated with fiber intake.

PMID- 9626488
TI  - Edible films and coatings: tomorrow's packagings: a review.

PMID- 9626489
TI  - The thiobarbituric acid (TBA) reaction in foods: a review.
AB  - The wide diffusion of 2-thiobarbituric acid (TBA) in the scientific literature is
      due to the TBA assay, or TBA test, which has been employed in the determination
      of autoxidative alterations of fats and oils. Two processes occur in
      autoxidation, generally: the free radical and the photo-oxidation mechanisms. The
      better studied is the free radical mechanism. The hydroperoxiepidioxides and
      bicycloendoperoxides are malonaldehyde (MDA) precursors. The absorption spectrum
      obtained with oxidized fatty foods is like the spectrum obtained when TBA and MDA
      react. However, during the secondary phase of the autoxidation process other
      aldehydes (alkanals, 2-alkenals, dienals) are formed which react with TBA, and
      they are responsible for off-flavors. Three kinds of pigments (yellow, orange,
      red adducts) are involved. Also, aromatic aldehydes, which constitute the flavor
      profile of diverse fruits and essential oils, form with TBA the characteristic
      arylidene-2-TBA acids. Other substances, such as ketones, ketosteroids, acids,
      esters, sugars, imides and amides, amino acids, oxidized proteins, pyridines,
      pyrimidines, and vitamins can react with TBA; they are named TBARS (substances
      that react with TBA), and form principally in meats and meat derivatives. Several
      organic or bio-organic acids, as shikimic and sorbic acids, react photometrically
      with TBA if a Malaprade reaction takes place before. A structural study of the
      red adduct TBA-MDA has been carried out.

PMID- 9626490
TI  - The role of muscle proteases and lipases in flavor development during the
      processing of dry-cured ham.
AB  - The processing of dry-cured ham is very complex and involves numerous biochemical
      reactions that are reviewed in this article. Muscle proteins undergo an intense
      proteolysis, resulting in a great number of small peptides and high amounts of
      free amino acids. The enzymes responsible of these changes are proteinases
      (cathepsins B, D, H, and L and, to a less extent, calpains) and exopeptidases
      (peptidases and aminopeptidases). Muscle and adipose tissue lipids are also
      subject to intense lipolysis, generating free fatty acids by the action of
      lipases that, in a second stage, are transformed to volatiles as a result of
      oxidation. Sensory profiles of dry-cured ham are strongly affected by these
      enzymatic reactions. In addition, the activity levels of the muscle enzymes
      significantly depend on the properties of raw ham, such as age and crossbreeding
      as well as the process conditions such as temperature, time, water activity,
      redox potential, and salt content. Thus, the control of the muscle enzyme
      systems, mainly proteases and lipases, is essential for the standardization of
      the processing and/or enhancement of flavor quality of dry-cured ham.

PMID- 9626491
TI  - Peripheral vascular disease, Part 1.

PMID- 9626492
TI  - Gene trapping--a preface.

PMID- 9626493
TI  - Efficiency assessment of the gene trap approach.
AB  - The trapping of genes in murine embryonic stem (ES) cells offers three features
      in one experimental approach: 1) analysis of the expression patterns of unknown
      genes by using a simple staining method, 2) rapid cloning of unknown genes, and
      3) generation of mutant mouse lines. We performed a gene trap screen aimed at the
      discovery of new genes regulating embryonic development. We have processed 209
      gene trap events for expression patterns in chimeric murine embryos. Randomly
      tested, beta-galactosidase-positive ES cell clones resulted in vivo in 35% gene
      trap events showing no beta-galactosidase activity, 39% gene trap events with
      ubiquitous beta-galactosidase activity, and 26% gene trap events showing beta
      galactosidase activity restricted to specific cell types or organs. In vitro
      preselection reduced gene trap events with ubiquitous beta-galactosidase activity
      to 10% and increased the gene trap events with restricted beta-galactosidase
      activity to 64%, making the screening procedure for genes expressed in a
      restricted manner 2.5-fold more efficient. In five of the seven gene trap
      insertions into genes in which the expression pattern during embryogenesis was
      known, the beta-galactosidase marker gene reproduced faithfully the expression
      pattern of the trapped gene. 5'-Rapid amplification of cDNA ends (5'-RACE) of 28
      gene trap events revealed 19 novel mouse genes, 8 known mouse genes, and 1 random
      transsplicing event. Twelve of the 25 mouse lines that crossed to homozygosity
      showed overt abnormalities. The genomic structure was investigated in four of
      these gene trap events, which caused obvious abnormalities. In all four cases,
      the splice-acceptor gene trap construct was inserted into an exon. One of the 13
      gene trap events that did not result in overt abnormalities was examined for the
      presence of wild-type mRNA. Homozygous animals were found to produce normal
      levels of wild-type mRNA. Evidently, gene trapping does not always provide all
      three of the features mentioned above. In this paper, we discuss the efficiency
      of gene trapping and ways in which some problems may be overcome.

PMID- 9626494
TI  - Large-scale screening for developmental genes in embryonic stem cells and
      embryoid bodies using retroviral entrapment vectors.
AB  - Mammalian development is orchestrated by a variety of cellular proteins with
      expression that is regulated precisely. Although some of the genes encoding these
      factors have been identified, largely by homology to those of simpler organisms,
      the majority of them presumably remain unknown. We report here on the results of
      a large-scale genetic screen that can potentially lead to the identification of
      many of these unidentified genes in mice. The method we developed takes advantage
      of the fact that many of the factors that regulate early development are
      expressed at highly specific stages of early embryogenesis. We therefore
      established a method for tagging candidate developmental genes by virtue of their
      expression in a stage-specific manner during formation of embryoid bodies without
      a bias for their expression in undifferentiated embryonic stem (ES) cells. Of
      2,400 ES cell clones with random insertions of retroviral vectors carrying a
      human placental alkaline phosphatase reporter gene (AP), 41 clones exhibited
      stage-specific reporter gene expression during embryoid body formation. The
      majority of these insertions were in genes that are not expressed in
      undifferentiated ES cells. Eleven ES cell clones with characteristic patterns of
      AP reporter gene expression in vitro were chosen for further examination in vivo
      for AP expression in developing embryos. Ten ES cell clones exhibited AP
      expression between day 7.5 and day 10.5 of development. Clones that showed
      restricted reporter gene expression in vitro also exhibited similar temporally
      and spatially restricted AP expression in vivo. Sequence analysis of genomic DNA
      flanking several vector insertions and corresponding cDNAs suggested that several
      of the insertions identified a previously unidentified gene. Thus, screening for
      reporter gene expression during embryoid body formation provides an efficient
      means of enriching clones that contain vector insertions into potentially novel
      genes that are important for regulating different stages of early
      postimplantation development.

PMID- 9626495
TI  - Gene trap expression and mutational analysis for genes involved in the
      development of the mammalian nervous system.
AB  - We have used a large-scale gene trap approach for the isolation and mutation of
      genes that might play roles in the developing nervous system. After in vitro
      integration of two different gene trap vectors (pGT1.8geo: Skarnes et al. [1995]
      Proc. Natl. Acad. Sci. USA 92:6592-6596; IRES beta geo: Chowdhury et al. [1997]
      Nucleic Acids Res. 25:1531-1536) in mouse embryonic stem (ES) cell lines, we
      created 64 transgenic mouse lines. The expression analysis of the reporter gene
      during embryogenesis of heterozygous embryos revealed 47 lines with a variety of
      patterns. Around one-third (36%) of these gene trap lines showed spatiotemporal
      expression that was either restricted predominantly in the developing nervous
      system (11 lines; 17%) or widespread but with very high levels of expression in
      the nervous tissue (12 lines; 19%). In most cases, a correlation was found
      between the in vitro and the in vivo patterns of the reporter gene expression.
      Thus far, preliminary mutant analysis of 16 gene trap lines with potentially
      interesting expression patterns in the developing nervous system showed that mice
      homozygous for eight (50%) insertions were lethal, whereas the homozygous mice
      from five gene trap lines (31%) showed a lower than expected Mendelian ratio of
      live homozygous animals. Analysis of beta-galactosidase reporter gene expression
      during embryogenesis has shown that four transgenic lines are useful lacZ in situ
      markers for specific regions of the developing nervous system. Here, we discuss
      some in vivo and in vitro selection criteria that may increase the number of the
      trapped genes potentially involved in the control of neural development and some
      future strategies to improve further the efficiency of the gene trap approach.

PMID- 9626496
TI  - The mouse Gtl2 gene is differentially expressed during embryonic development,
      encodes multiple alternatively spliced transcripts, and may act as an RNA.
AB  - We have isolated a novel mouse gene (Gtl2) from the site of a gene trap
      integration (Gtl2lacZ) that gave rise to developmentally regulated lacZ
      expression, and a dominant parental-origin-dependent phenotype. Heterozygous
      Gtl2lacZ mice that inherited the transgene from the father showed a proportionate
      dwarfism phenotype, whereas the penetrance and expressivity of the phenotype was
      strongly reduced in Gtl2lacZ mice that inherited the transgene from the mother.
      Gtl2 expression is highly similar to the beta-galactosidase staining pattern, and
      is down-regulated but not abolished in mice carrying the Gtl2lacZ insertion. In
      early postimplantation embryos, Gtl2 is expressed in the visceral yolk sac and
      embryonic ectoderm. During subsequent development and organogenesis, Gtl2
      transcripts are abundant in the paraxial mesoderm closely correlated with
      myogenic differentiation, in parts of the central nervous system, and in the
      epithelial ducts of developing excretory organs. The Gtl2 gene gives rise to
      various differentially spliced transcripts, which contain multiple small open
      reading frames (ORF). However, none of the ATG codons of these ORFs is in the
      context of a strong Kozak consensus sequence for initiation of translation,
      suggesting that Gtl2 might function as an RNA. Nuclear Gtl2 RNA was detected in a
      temporally and spatially regulated manner, and partially processed Gtl2
      transcripts were readily detected in Northern blot hybridizations of
      polyadenylated RNA, suggesting that primary Gtl2 transcripts are differently
      processed in various cell types during development. Gtl2 transcript levels are
      present in parthenogenic embryos but may be reduced, consistent with the pattern
      of inheritance of the Gtl2lacZ phenotype.

PMID- 9626497
TI  - Dmd(mdx-beta geo): a new allele for the mouse dystrophin gene.
AB  - During a gene trap screen, an insertion of the gene trap vector into the
      dystrophin gene, creating a new allele for the Dmd gene, has been discovered.
      Because the ROSA beta geo vector was used, the new allele is called Dmd(mdx-beta
      geo). The insertion occurred 3' of exon 63 of the dystrophin gene, resulting in a
      mutation that affects all presently known dystrophin isoforms. In contrast to
      spontaneous or ENU-induced alleles, Dmd(mdx-beta geo) can be used to follow
      dystrophin expression by staining for beta-galactosidase activity. The high
      sensitivity of this method revealed additional and earlier expression of
      dystrophin during embryogenesis than that seen previously with other methods.
      Dystrophin promoters are active predominantly in the dermamyotome, limb buds,
      telencephalon, floor plate, eye, liver, pancreas anlagen, and cardiovascular
      system. Adult Dmd(mdx-beta geo) mice show reporter gene expression in brain, eye,
      liver, pancreas, and lung. In skeletal and heart muscle, beta-galactosidase
      activity is not detectable, confirming Western blot data that indicate the
      absence of the mutant full-length protein in these tissues. Hemizygous Dmd(mdx
      beta geo) mice show muscular dystrophy with degenerating muscle fibers, cellular
      infiltration, and regenerated muscle fibers that have centrally located nuclei.
      Some mutant animals develop a dilated esophagus, probably due to constriction by
      the hypertrophic crura of the diaphragm.

PMID- 9626498
TI  - Crouzon-like craniofacial dysmorphology in the mouse is caused by an insertional
      mutation at the Fgf3/Fgf4 locus.
AB  - Retroviral insertional mutagenesis by means of ES cells has resulted in a new
      autosomal dominant mutation causing craniofacial dysmorphology in the mouse
      (Bulgy-eye, Bey). Heterozygous Bey mice are viable and fertile but show facial
      shortening with increased interorbital distance and precocious closure of several
      cranial sutures (craniosynostosis). These features provide a murine phenocopy for
      a large class of human craniofacial dysmorphology syndromes associated with
      craniosynostosis, particularly Crouzon syndrome. The retroviral vector
      integration responsible for the Bey mutation is inserted in the intragenic region
      between Fgf3 and Fgf4. Transcript analysis demonstrates that expression of both
      Fgf3 and Fgf4 is up-regulated in the cranial sutures of Bey mice. Many of these
      human craniosynostosis syndromes are caused by mutations in the extracellular
      domain of receptors for fibroblast growth factors that result in constitutive
      receptor activation. Our data confirm that fibroblast growth factor signalling
      pathways are involved in craniofacial development and suggest that some human
      malformation pedigrees or sporadic craniosynostosis may be caused by mutations
      that deregulate expression of the Fgf ligands.

PMID- 9626499
TI  - Distribution of a murine protein tyrosine phosphatase BL-beta-galactosidase
      fusion protein suggests a role in neurite outgrowth.
AB  - We have generated a gene trap insertion into the protein tyrosine phosphatase-BL
      (PTP-BL) locus, which produces a fusion of the N-terminal half of PTP-BL with
      beta-galactosidase. During development, beta-galactosidase activity was seen in
      all epithelial cells: strong staining was observed in the stomach and kidney
      epithelium, the ependymal layer of the central nervous system, and the surface
      ectoderm. Particularly prominent beta-galactosidase activity was seen in the
      peripheral nervous system, which correlated with neurite outgrowth. In epithelial
      cells, staining was seen in the apical portion of the cells. In nerves, beta
      galactosidase activity was associated with growth cones as well as with Schwann
      cells. This suggests that the amino-terminal portion of PTP-BL contains sequences
      sufficient to target the fusion protein to specific subcellular compartments. In
      situ hybridization with a PTP-BL probe demonstrated that all tissues in which
      beta-galactosidase activity was seen were genuine sites of expression of the PTP
      BL gene, although differences in the stability of the PTP-BL protein and the PTP
      BL-beta-galactosidase fusion protein may exist. The distribution of beta
      galactosidase activity in the peripheral nervous system, together with the
      structure of the wild-type protein, suggests that this phosphatase may have a
      role in regulation of the cytoskeleton during the development of the peripheral
      nervous system.

PMID- 9626500
TI  - Compensation for a gene trap mutation in the murine microtubule-associated
      protein 4 locus by alternative polyadenylation and alternative splicing.
AB  - One of the features expected of the gene trap approach is the functional mutation
      of a gene, allowing its loss-of-function phenotype analysis. We have mutated the
      murine microtubule-associated protein 4 (MAP-4) locus by inserting a splice
      acceptor gene trap construct. Because the MAP-4 gene has been cloned, sufficient
      information is available to investigate the efficiency of the gene trap insertion
      in disrupting the protein-coding region. The fusion mRNA contains the first 905
      bases of the MAP-4 mRNA and is expected to code for a truncated, nonfunctional
      MAP-4 protein missing, among others, the microtubule-binding domain. Activity of
      the lacZ marker gene of the gene trap construct was observed in all tissues
      throughout development and in all cells examined in adult animals. However, some
      cells and tissues showed higher levels of activity than others: for example,
      blood vessel endothelium, heart, aspects of the developing nervous system,
      surface ectoderm of embryonic day 11.5 embryos, and the ependymal layer and blood
      vessel endothelium in adult brain. MAP-4 binds to microtubules and is thought to
      modulate their stability. It is expressed differentially in different tissues as
      5.5-kb, 6.5-kb, 8-kb, 9-kb, and 10-kb mRNA species from a single copy gene in
      mice. Northern hybridization with a 5', MAP-4-specific probe revealed a 3.3-kb
      splice variant, which has not been described previously, that was expressed as
      the most abundant MAP-4 mRNA species in the brain but not in other tissues. Mice
      homozygous for the reported gene trap insertion in the MAP-4 locus (MAP-4gt/gt)
      are viable and appear to be phenotypically normal. They exhibited normal levels
      of all MAP-4 mRNA species in brain and kidney, showing that the simian virus 40
      polyadenylation signal of the gene trap construct was ignored and also showing
      compensation for the gene trap insertion by splicing around the gene trap
      construct.

PMID- 9626501
TI  - Gene trap integrations expressed in the developing heart: insertion site affects
      splicing of the PT1-ATG vector.
AB  - We describe the characterisation of three gene trap integrations in embryonic
      stem cells in which the lacZ reporter gene is repressed by retinoic acid (RA) in
      vitro and is expressed in the developing heart in vivo. In one of these, the gene
      trap vector has integrated into a gene that is located on chromosome 17 and is
      homologous to the human transcription factor gene, TFEB. Embryonic and adult
      cardiac expression of both the fusion transcript and the endogenous gene was
      confirmed. However, we show that the integration has not resulted in a null
      allele, because wild type transcripts, possibly resulting from splicing around
      the vector, are observed in homozygous tissue. The other two cardiac-expressing
      gene trap integrations have occurred into exons on chromosomes 1 and 5 and have
      used cryptic donor sites within the vector to generate functional fusion
      transcripts. One of these exon integrations results in a lethal neonatal
      phenotype.

PMID- 9626502
TI  - Disruption of genes regulated during hematopoietic differentiation of mouse
      embryonic stem cells.
AB  - A retroviral gene trap vector (U3Tkneo) that selects for integrations in or near
      expressed 5' exons has been used to identify genes that are repressed during
      hematopoietic differentiation of mouse totipotent embryonic stem cells. The
      vector contains coding sequences for an HSV-thymidine kinase/neomycin
      phosphotransferase fusion protein in the U3 region of a Moloney murine leukemia
      virus LTR and allows selection for (G418) and against (Ganciclovir; GC) U3 gene
      expression. A total of 208 neomycin-resistant clones were isolated following
      infection with U3tkneo and screened for integrations into regulated genes by
      using a two-step, semisolid culture system that supports hematopoietic
      differentiation. Two clones contained U3Tkneo integrations in genes that were
      repressed selectively in hematopoietic cells. Analysis of upstream proviral
      flanking sequences indicated that both integrations occurred into unknown genes.
      One up-stream sequence identified a cellular transcript that was expressed
      differentially in the kidneys and liver of adult mice. When this fusion gene was
      passaged to the germ line, homozygous offspring with nearly null mutations were
      obtained. However, mutant mice were normal, suggesting that potential loss of
      function phenotypes are subtle and may be restricted to the kidneys and the
      liver.

PMID- 9626503
TI  - Disruption of murine alpha-enolase by a retroviral gene trap results in early
      embryonic lethality.
AB  - Gene trapping with the retroviral ROSA beta geo vector was used to generate lines
      of mice carrying disrupted genes. Both cDNA and genomic flanks have been cloned
      from a number of these lines. One mutation has been shown to disrupt the alpha
      enolase gene by insertion of the splice-trap vector into the first intron. In
      adult mice, lacZ expression was detected only in testes. Embryonic expression was
      detected from 10.5-day postcoitum embryos and was seen as a diffuse staining
      pattern over much of the embryo, consistent with the housekeeping gene function
      of alpha-enolase. This mutation results in an early recessive embryonic
      lethality. Mice heterozygous for the mutation have no obvious phenotype.
      Mutations of this gene in humans are reported to be associated with rare
      autosomal-dominant, non-spherocytic haemolytic anaemia. This phenotype is not
      reproduced in mice heterozygous for this mutation.

PMID- 9626504
TI  - Bodenin: a novel murine gene expressed in restricted areas of the brain.
AB  - A gene trap screen designed to isolate novel mouse genes involved in nervous
      system development was performed. Here, we describe the isolation and
      characterization of a novel gene, bodenin, which is expressed in restricted areas
      of the brain. beta-Galactosidase marker gene activity was detected in the embryo
      at the start of organogenesis (embryonic day 8.5; E8.5). Staining gradually
      became stronger until E12.5, when embryos exhibited widespread expression. In
      brains of newborn and adult mice, beta-galactosidase staining was confined
      predominantly to forebrain structures. Transcriptional activity was also observed
      in kidney, liver, lung, heart, skeletal muscle, and testes. Part of the trapped
      gene was isolated by 5'-rapid amplification of cDNA ends (5'-RACE). Isolation and
      sequencing of the complete cDNA revealed an unknown gene encoding a 200 amino
      acid protein. Comparison with published sequences showed 94% amino acid identity
      to a human integrin cytoplasmic domain-associated protein. Mice homozygous for
      the mutation were viable and did not exhibit any obvious abnormal phenotype.
      However, concealed phenotypic abnormalities cannot be excluded. The lack of
      readily visible abnormalities may also be due to functional compensation or to
      the production of low levels of wild-type protein in mice homozygous for the gene
      trap vector insertion. Nevertheless, the restricted expression of bodenin in the
      brain of newborn and adult mice suggests a role for this novel gene in the
      developing and mature central nervous system.

PMID- 9626505
TI  - Aquarius, a novel gene isolated by gene trapping with an RNA-dependent RNA
      polymerase motif.
AB  - In a retinoic acid (RA) gene trap screen of mouse embryonic stem (ES) cells, a
      novel gene, named Aquarius (Aqr), was identified and characterized. The
      promoterless lacZ marker was used to trap the genomic locus and to determine the
      expression pattern of the gene. Aqr transcripts are strongly induced in response
      to RA in vitro. During embryogenesis, Aqr is expressed in mesoderm, in the neural
      crest and its target tissues, and in neuroepithelium. Expression was first
      detected at 8.5 days postcoitum, when neural crest cells are visible at the
      lateral ridges of the neural plate. The gene-trapped Aqr locus was transmitted
      through the mouse germ line in three genetic backgrounds. In the F2 generation,
      the expected mendelian ratio of 1:2:1 was observed in all backgrounds, indicating
      that homozygous mice are viable. Homozygotes are normal in size and weight and
      breed normally. The gene trap insertion, however, does not seem to generate a
      null mutation, because Aqr transcripts are still present in the homozygous mutant
      animals. The Aqr open reading frame has weak homology to RNA-dependent RNA
      polymerases (RRPs) of the murine hepatitis viruses and contains an RRP motif. Aqr
      was mapped to mouse chromosome 2 between regions E5 through F2 by using
      fluorescence in situ hybridization analysis.

PMID- 9626506
TI  - Gene trap insertion into a novel gene expressed during mouse limb development.
AB  - Gene trapping is a useful method to identify new genes involved in development.
      Here we describe the spatiotemporal expression of a gene identified in a gene
      trap screen. This gene is first expressed at 9.5 days postcoitum (E9.5) in the
      forelimbs and in the branchial arches region. At E11.5, expression was detected
      in the stomach, genital bud, and pharyngeal epithelium. At later stages,
      expression includes the hair follicles, whereas the expression in the stomach and
      pharynx disappears. We performed 5'-rapid amplification of cDNA ends (RACE) to
      amplify and clone a partial cDNA of the endogenous sequence fused to the lacZ
      reporter gene. The sequence did not reveal any similarity to known sequences and
      was named paddy. The expression pattern suggests multiple roles during limb
      development. The early phase of expression, for instance, correlates with
      anteroposterior (A/P) regionalization. In contrast to other molecules involved in
      A/P polarization, paddy expression fades away distally as the bud elongates. This
      suggests that expression of paddy in late stages does not depend on apical
      ectodermal ridge (AER) and zone of polarizing activity (ZPA) signaling and is
      probably involved in posterior determination in more proximal regions of the
      limb.

PMID- 9626507
TI  - Efficient poly A trap approach allows the capture of genes specifically active in
      differentiated embryonic stem cells and in mouse embryos.
AB  - Special vectors have been constructed that allow the trapping of genes in mouse
      embryonic stem (ES) cells. These vectors generally contain the neomycin
      phosphotransferase (neo) gene for selection and the beta-galactosidase (beta-gal)
      gene as a marker. Promoterless vectors can be used to identify genes that are
      active in undifferentiated ES cells. To also have access to genes that are
      inactive in totipotent ES cells, we constructed a polyadenylation (poly A) trap
      vector in which the expression of a poly A less neo gene is driven by a
      constitutive promoter, whereas the expression of beta-gal depends on the trapped
      sequences. We demonstrate here that this vector integrates with a high frequency
      into transcription units and that it traps genes with very different expression
      patterns in vitro and in vivo. The vector integrates efficiently into
      transcription units that are inactive in undifferentiated ES cells and which can
      be activated through in vitro differentiation. Furthermore, in vivo expression
      patterns demonstrate that this vector integrates into genes that exhibit a highly
      specific temporal and spatial expression pattern during embryogenesis.

PMID- 9626508
TI  - Fine-needle aspiration cytology of tongue swellings: a study of 75 cases.
AB  - Tongue swellings and growths are traditionally evaluated by surgical biopsy. Most
      of them, however, are easily accessible by fine-needle aspiration (FNA). We
      reviewed 75 lesions presenting as tongue swellings, which were examined by fine
      needle aspiration cytology (FNAC) in our institutions over a period of 11 yr. The
      lesions included 17 malignant tumors: 12 cases of squamous carcinoma (SQC), 2
      metastases, and 3 non-Hodgkin's lymphomas (NHL). In addition, 15 benign tumors
      and 43 nonneoplastic benign conditions were found. Thirteen of the 17 malignant
      lesions were diagnosed cytologically as malignant, 3 as suspicious for
      malignancy, and 1 as atypical, with biopsy recommended. There were no false
      positive diagnoses. There were no clinical complications resulting from FNA. We
      conclude that FNAC of the tongue permits rapid and reliable diagnosis, and we
      recommend this method as the first diagnostic step in the evaluation of tongue
      swellings.

PMID- 9626509
TI  - Adenocarcinoma of the uterine cervix associated with pregnancy: a retrospective
      10-year investigative study.
AB  - We conducted chart reviews on 56 women of childbearing age (up to age 40)
      diagnosed with adenocarcinoma of the cervix. Of these, 16 (30%) were identified
      as having pregnancy-associated disease. Eleven of the 16 were diagnosed with
      invasive adenocarcinoma (i.a.) and 5 with adenocarcinoma in situ (AIS). Prior
      cervicovaginal smears were available on 12 of the 16 women; of these, only one
      was reported as showing cancer. Mean age at time of diagnosis of AIS and IA in
      the pregnant women was 33 and 30.3 yr and in the nonpregnant women, 30.6 and 32.8
      yr, respectively. We found an absolute increase in the number of cases of
      adenocarcinoma of the cervix over the past decade in both pregnant and age
      matched nonpregnant women of childbearing age (1984-1988: 6, pregnant; 12,
      nonpregnant; 1989-1994: 10, pregnant; 28, nonpregnant) but no significant
      difference in the percentages of the disease in pregnant vs. nonpregnant
      populations (Z = 0.95). We also found an overall increase in the number of
      diagnosed cases of adenocarcinoma of the cervix (especially in situ) in both
      study groups over the same time period (1984-1988: 3, AIS; 14, IA; 1989-1994: 15,
      AIS; 24, IA).

PMID- 9626510
TI  - Detection of apoptotic cells in cytology specimens: an application of TdT
      mediated dUTP-biotin nick end labeling to cell smears.
AB  - We applied TdT-mediated deoxyuridine triphosphate (dUTP)-biotin nick end labeling
      (TUNEL) to cytologic smears in order to detect the cells undergoing apoptosis.
      These smears were obtained by scraping the cut surface of 9 cases of carcinoma,
      including renal-cell carcinoma (3 cases), esophageal squamous-cell carcinoma (3
      cases), and gastric adenocarcinoma (3 cases), and were fixed and prepared by
      different methods. The results were also compared with those of tissue sections.
      TUNEL in smears was generally associated with higher background nuclear stain
      than in tissue sections. Smears that were fixed in 4% or 8% paraformaldehyde or
      absolute methanol exhibited results comparable with those of tissue sections,
      with minimum background in all cases examined. There were no significant
      differences in TUNEL labeling index among tissue sections and smears fixed in 4%
      or 8% paraformaldehyde or in absolute methanol. Smears treated in Carnoy's
      fixative (3:1 methanol:acetic acid) and air-dried smears demonstrated a higher
      background. TUNEL positivity could not be detected in slides decolorized from May
      Grunwald-Giemsa stain. Markedly high background, which may occur as a result of
      artifactural DNA breaks, was also observed in slides decolorized from
      Papanicolaou stain, in which TUNEL-positive cells could be evaluated only in 3/8
      cases. Application of the TUNEL method to cytology specimens has disadvantages or
      limitations compared to its application to histological sections, but the method
      is considered the most suitable one for detecting cells undergoing apoptosis in
      cytology materials.

PMID- 9626511
TI  - Basal-cell carcinoma: cytologic and immunocytochemical findings in fine-needle
      aspirates.
AB  - The smears of fine-needle aspirates corresponding to 137 histologically proven
      basal-cell carcinomas (BCCs) were reviewed. Satisfactory for evaluation were 127
      smears; the remaining 10 were unsatisfactory. In 124 cases (97.6%), the cytologic
      diagnoses coincided with the histologic ones. The remaining 3 were false
      negatives, and the subsequent histologic correlation demonstrated superficial BCC
      missed by the needle. The cytologic criteria that permitted a diagnosis of BCC
      were: variable-sized and irregular-shaped cohesive epithelial clusters, round to
      oval monomorphic nuclei, bland chromatin pattern, and sparse cytoplasm. In 35
      cases, a panel of antibodies was used in the smears and in the respective
      histologic sections. Epithelial clusters of BCC showed an intense and diffuse
      positivity for AE-3 and BerEP4, while UEAI and AE-1 were negative. Although HMB45
      and S100-A tested negative in the epithelial clusters, a faint and sparse focal
      positivity for HMB45 and S-100A was seen in some clusters. This positivity is
      believed to correspond to just a few normal melanocytes and Langerhans cells
      trapped in the neoplastic epithelial clusters. In the histologic correlates, the
      same results were obtained, although HMB45 positivity was more conspicuous at the
      periphery of the neoplastic nests.

PMID- 9626512
TI  - Needle aspiration cytology of metastatic high-grade transitional-cell carcinomas
      of the urinary tract.
AB  - We reviewed 4 cases of high-grade transitional-cell carcinoma (TCC) of the
      urinary tract with solitary pulmonary metastases that were studied by
      transthoracic needle aspiration biopsy cytology. There were two grade II and two
      grade III TCCs. The two grade II tumors yielded, in needle aspirates, syncytial
      tumor-cell clusters showing ill-defined, granular cytoplasm and slightly
      pleomorphic nuclei with inconspicuous nucleoli. In one case the tumor-cell
      cluster showed a focal acinar arrangement, mimicking cells of an adenocarcinoma.
      In both cases the electron microscopy (EM) study of aspirated tumor cells
      revealed epithelial cells with well-formed cell junctions, intracytoplasmic
      vesicles, apical short microvilli, and focal interdigitation of lateral cell
      membranes, suggesting a urothelial neoplasm. The two grade III TCCs yielded, in
      needle aspirates, pleomorphic malignant cells singly and in small clusters,
      showing well-defined, granular cytoplasm and pleomorphic nuclei containing
      prominent nucleoli, suggesting a poorly differentiated adenocarcinoma or an
      anaplastic large-cell carcinoma. By EM examination the aspirated tumor cells from
      one case revealed well-formed cell junctions, intracytoplasmic vesicles, poorly
      formed microvilli, and focal interdigitation of lateral cell membranes,
      suggesting a urothelial differentiation. In the other case the tumor cells were
      pleomorphic cells with occasional cell junctions and no ultrastructural features
      as seen in the other 3 cases of TCC. The tumor cells from the two grade II TCCs
      showed strong immunopositive reaction with keratin 7 antibody and weakly positive
      reaction with carcinoembryonic antigen antibody (CEAA), while those of the two
      grade III TCCs displayed only a weak and focal immunopositive staining with
      keratin 7 antibody and strong reaction with CEAA.

PMID- 9626513
TI  - Cytologic correlates of papillary immature metaplasia (immature condyloma) of the
      cervix.
AB  - Papillary immature metaplasia (PIM) of the cervix (immature condyloma) is a
      variant of low-grade squamous intraepithelial lesions (LSIL). It is frequently
      associated with human papillomavirus (HPV) types 6 and 11. The purpose of this
      study was to characterize the cytologic changes associated with this lesion. We
      analyzed 10 cases of PIM from our files and reviewed the Papanicolaou smears
      taken proximate to the time of the biopsy. Four cases had either reactive
      epithelial changes (2 cases) or cytologic findings typical of low-grade SIL, with
      koilocytosis (2 cases). Six cases displayed a spectrum of metaplastic cells with
      varying maturation that ranged from atypical reactive cells to atypical immature
      metaplastic cells. Binucleation was common. Some cells exhibited features
      characteristic of SIL, although the degree of nuclear atypia generally was less
      than that associated with high-grade SIL. Papanicolaou smears from all cases were
      interpreted as atypical (ASCUS) metaplasia or low-grade SIL. Follow-up biopsy in
      one case revealed a PIM in association with a high-grade SIL, the latter
      undiagnosed by smear alone. PIM is a distinct histologic entity that can present
      with a spectrum of cytologic findings. Its recognition histologically can resolve
      some cytologic/histologic discrepancies. Confusion with an immature HSIL or
      atypical immature metaplasia can occur in some instances and the diagnosis of PIM
      by cytology alone is not recommended, unless the diagnosis is qualified.

PMID- 9626514
TI  - Metastatic squamous-cell carcinoma in pericardial effusion: report of four cases,
      two with cardiac tamponade.
AB  - For reasons unknown, metastatic squamous-cell carcinoma is a rare cause of
      pleural effusions and is even less common in pericardial effusions. A review of
      all pericardial effusions examined in the Cytology Service at Montefiore Medical
      Center over a 15-year (1980-1994) period was undertaken (N = 251). Four cases
      with metastatic squamous-cell carcinoma were identified among 39 malignant
      effusions. Two patients with metastatic squamous-cell carcinoma presented with
      cardiac tamponade, and the other two cases had progressive cardiac failure. The
      diagnostic cells on cytology evaluation were scant in all four cases but
      exhibited classical features of metastatic squamous carcinoma, such as
      cytoplasmic keratinization, intercellular bridges, and occasional "pearl"
      formation. Pericardial biopsies available in three patients, two with cardiac
      failure and one with cardiac tamponade, were negative. In all four cases the
      primary tumor was a bronchogenic carcinoma. Metastatic squamous-cell carcinoma is
      an uncommon cause of pericardial effusion and usually indicates the presence of a
      bronchogenic carcinoma with a rapidly fatal outcome. Cytologic examination of
      pericardial fluid is essential in the evaluation of such patients.

PMID- 9626515
TI  - Utility of fine-needle aspiration in the diagnosis of panniculitis.
AB  - This is a retrospective reassessment of the most important cytopathologic
      features of 23 FNA smears with a cytologic diagnosis of panniculitis (PN).
      Patients were sent by clinicians. Clinical diagnoses were as follows: 16
      suspicious of PN; three cutaneous metastases of an extracutaneous primary
      neoplasm; four with no clinical diagnosis. Thirteen cases were subsequently
      submitted to histopathologic study. The following cytoarchitectural patterns were
      found to be very useful for the cytologic diagnosis of PN: adipocytes
      intermingled with foamy histiocytes, donut-like granulomas, aggregates of
      adipocytes intermingled with plump histiocytes, a granular basophilic background
      forming a lattice-like pattern, and well-formed granulomas with or without
      multinucleated giant cells. Inflammatory cells could be seen combined with any of
      these cytoarchitectural patterns. FNA does not pretend to replace excisional
      biopsy as the diagnostic procedure for these entities but it is a very useful
      diagnostic tool in certain cases: for confirming the recurrence of PN previously
      diagnosed by histology, for evaluating the onset of subcutaneous nodules in
      patients with a non-cutaneous malignant primary neoplasm, for evaluating
      cutaneous nodules with no clinical suspicion, and for confirming a clinical
      diagnosis of PN and differentiating it from other entities that mimic PN
      clinically.

PMID- 9626516
TI  - Detection of telomerase expression in fine-needle aspirations and fluids.
AB  - The cytologic examination of fine-needle aspirates and fluid specimens is plagued
      by a persistent false negative rate. The rate of false negative results will be
      decreased if sensitive molecular assays can be developed to detect cytologically
      malignant cells. The current study investigated telomerase expression as a
      potential marker of malignancy, using the telomeric repeat amplification protocol
      (TRAP) in fine-needle aspirates and fluid specimens. TRAP was performed on 24
      fine-needle aspirate and 24 fluid specimens from different body sites and of
      different histological diagnoses. We found that 6 of 12 fine-needle aspirate
      specimens that were cytologically positive for malignant cells expressed
      telomerase activity, while no specimens that were cytologically suspicious for
      malignancy, atypical, or negative tested positive for telomerase activity. Of the
      fluid specimens, 4 of 6 cytologically positive cases and 1 of 18 cytologically
      negative cases expressed telomerase. Seven of eight telomerase negative,
      cytologically positive specimens contained only rare malignant cells in a very
      bloody background. Peripheral blood contamination is a possible pitfall in the
      TRAP assay, as applied in the current study, because the assay is standardized to
      protein concentration that may be derived from lysed red blood cells. We conclude
      that with further technical refinement, the TRAP assay could become a useful
      adjunct in the cytologic examination of fine-needle aspirates and fluid samples.

PMID- 9626517
TI  - Fine-needle aspiration cytology and immunocytochemistry of Hodgkin's disease,
      suppurative type.
AB  - We describe 3 cases of Hodgkin's disease (HD) of unusual suppurative type, which
      were diagnosed on fine-needle aspirates. The smears were dominated by
      neutrophils, macrophages, and cellular debris. Only a few large, atypical cells
      of Hodgkin and Reed-Sternberg type were observed. The differential diagnoses of
      such smears include infectious mononucleosis, tuberculosis, metastatic lymph node
      involvement, non-Hodgkin's large-cell anaplastic Ki-1-positive lymphomas, T-cell
      rich B-cell lymphomas, and peripheral T-cell lymphomas of mixed type.
      Immunocytochemistry identified the large atypical cells as CD 30 (BerH2)-positive
      and negative for CD 45 (LCA) in cytospin material from 2 patients, which allowed
      a conclusive diagnosis of HD.

PMID- 9626518
TI  - Fine-needle aspiration cytology of a subareolar abscess of the male breast.
AB  - We report on the fine-needle aspiration (FNA) cytology of a subareolar abscess of
      the breast in a 45-yr-old man. The patient presented with a 1.5-cm mass in the
      subareolar region. FNA cytology demonstrated the presence of numerous anucleated
      squamous cells and a few small nucleated squamous cells as well as numerous
      neutrophils and some lymphocytes in the background. Histiocytes were also
      present, including some multinucleated foreign-body-type giant cells. No
      organisms were identified either with special stains or microbiologic cultures.
      The differential diagnosis of FNA of the male breast is presented, along with
      other lesions that can potentially contain either benign or malignant squamous
      cells in the aspirate. The correct FNA diagnosis of this unusual benign lesion
      involving the male breast should lead to the appropriate treatment. To the best
      of our knowledge, this is the first published report of FNA cytology of a
      subareolar abscess of the male breast.

PMID- 9626519
TI  - Infiltrating carcinoma arising in intraductal papillary-mucinous tumor of the
      pancreas.
AB  - A case of an infiltrating carcinoma arising in an intraductal papillary mucinous
      tumor (IPMT) of the pancreas was reported in a 60-yr-old man. Preoperative
      diagnosis of the carcinoma was established on the basis of fine-needle aspiration
      biopsy.

PMID- 9626520
TI  - Intraabdominal desmoplastic small round cell tumor: cytopathologic findings in
      two cases.
AB  - Intraabdominal desmoplastic small round cell tumor (DSRCT) is an extremely rare
      entity. This study describes fine-needle aspiration, ascitic fluid, and touch
      imprint cytomorphology of DSRCT in 2 patients with extensive abdomino-pelvic
      disease. Cytopathologic features were unique and showed good morphologic
      correlation with subsequent histology of the resected tumor. Immunocytochemical
      profile and differential diagnosis with other small round cell tumors in this age
      group are also discussed.

PMID- 9626521
TI  - Metastatic meningioma detected in pleural fluid.
AB  - Meningiomas with both malignant cytologic features and clinical behavior are
      rare. A 39-yr-old man with recurrent meningioma developed a pleural effusion
      which, on cytologic examination, contained metastatic meningioma. The diagnosis
      was subsequently confirmed histologically and ultrastructurally. In conclusion,
      metastatic meningiomas can retain meningotheliomatous cytologic features which
      may allow a diagnosis to be made of clinically unanticipated tumor spread.

PMID- 9626522
TI  - Entamoeba gingivalis identified in a left upper neck nodule by fine-needle
      aspiration: a case report.
AB  - We present a unique case of a 37-yr-old patient who underwent a left partial
      glossectomy, modified neck dissection, and radiation therapy in December 1990. In
      June 1991 the patient developed a 0.6 cm erythematous nodule in the left upper
      portion of her neck adjacent to the surgical scar. A fine-needle aspiration (FNA)
      of the nodule was performed. Cytologic examination revealed the presence of
      numerous organisms morphologically consistent with Entamoeba gingivalis. Although
      E. gingivalis can be found in specimens from the oral cavity, especially
      following radiation, it is rare to find these organisms within lesions of the
      head and neck region. In this case, it is believed that the patient had an
      increased number of organisms within her oral cavity secondary to radiation
      therapy. Radiation therapy also may have contributed to the formation of a
      fistula tract between the oral cavity and the surgical incision site which
      resulted in the formation of a small inflammatory nodule in the upper portion of
      the neck. The organisms could then travel from the oral cavity to the nodule in
      the neck thus explaining their presence in the FNA material.

PMID- 9626523
TI  - Role of fine-needle aspiration biopsy in breast lesions: analysis of a series of
      4,110 cases.
AB  - From January of 1990 to December of 1992, 6,954 consecutive cytologic breast fine
      needle aspiration biopsies (FNAB) were performed at the Laboratory of Pathology
      of Sant'Anna Hospital in Turin. Of these cases 62% were solid nodes, 35% were
      cystic nodes, and 2.7% were nonpalpable breast lesions (stereotaxic or ultrasound
      guided FNAB). We verified 4,110 cases: 913 cases underwent surgery and 3,197 were
      evaluated clinically, and/or cytologically, and/or with mammography at least 1 yr
      after the first diagnosis, or checked with the database of the Tumor Registry of
      Turin. In our series the FNAB sensitivity was 94.6%, specificity was 99.9%,
      accuracy was 98.8%, inadequate samples were 6.4%, false-negative rate was 1.4%,
      and false-positive rate was 0.3%. Our results indicate that the use of cell block
      improves sensitivity (from 85.2 to 94.6%) and strongly reduces false-negative
      results (from 3.9 to 1.4%). We conclude that FNAB is a discriminant procedure to
      the surgical biopsy in cases with clinical, ultrasound, or mammographic low or
      intermediate suspect, contributing to allow a high malignant/benign surgical
      biopsy rate and to reduce the need for frozen section diagnosis and medical
      costs.

PMID- 9626524
TI  - Immunocytochemical study in a case of adenomyoepithelioma of the breast.

PMID- 9626525
TI  - Cryptococcosis of the spleen: diagnosis by fine-needle aspiration cytology.

PMID- 9626526
TI  - Hyaluronate binding probe and CD44 in the differential diagnosis of malignant
      effusions: disappointing results in cytology material.

PMID- 9626527
TI  - Intranuclear cytoplasmic inclusions in gastric leiomyosarcoma.

PMID- 9626528
TI  - Environment and human health.
AB  - The great French surgeon Leriche once said, "To be in good health is to live in
      the silence of one's organs." For Nature it is exactly the contrary, but one must
      not forget that the environment may strike in silence, as demonstrated by the
      accidents at Jintsu and Minamata in Japan. Close to 10 years were necessary to
      understand the mechanisms of deadly cadmium and mercury intoxications in humans.
      Two kinds of stresses to humans may come from the environment: (i) infectious
      disease, and (ii) unexpected, more-or-less complex chemical reactions.

PMID- 9626529
TI  - Following sustainable development in relation to the north-south dialogue:
      ecosystem health and sustainability indicators.
AB  - The necessity for policy makers to follow the processes in relation to
      sustainability demands new tools for management, a major aspect of which is
      integrated attention to economic and sociocultural influences together with
      environmental issues. North and South have specific positions and
      responsibilities with regard to sustainable development, and management tools-
      such as indicators--should reflect them. Because the North-South dialogue is
      changing, different approaches to deal with the relationships are needed (e.g.,
      introduction of reciprocity, equity, and participation), while at the same time
      doing justice to the individual social, economic, and cultural characteristics of
      a country. Ecosystem health can be defined by requirements such as resilience,
      vigor, organization, and relations, which may be used for totally different
      systems as well. Because integration is a crucial aspect of the new tools, it is
      argued that integrating conceptual tools such as the environment-economy-society
      triangle, the PSIR-causality chain, and the Daly triangle in addition to other
      described integration tools is fundamental for decision makers. Crucial issues
      when dealing with indicators for sustainable development are integration and
      balance, attention to users, use of system characteristics, and understanding
      southern perspectives in this context.

PMID- 9626530
TI  - Ecological risk assessment: risk for what? How do we decide?
AB  - Ecological risk assessment is defined both in theory and in practice. To do it
      properly, we need to know what targets we are protecting, but these targets are
      not always obvious and clearly defined. The pragmatic approach, used most
      generally in the context of environmental protection legislation, is the risk
      quotient method. Two other approaches involving more transparency and ecological
      relevance are critically assessed. One is based on species sensitivity
      distributions; the other is based on generalized population dynamics. Challenges
      for the future are considered.

PMID- 9626531
TI  - Biodegradation: selection of suitable model.
AB  - Biodegradation of five herbicides, two acetanilides (propanil and propachlor),
      and three phenylureas (diuron, monuron, and fenuron) was analyzed in samples of
      river water during a period of 6-8 weeks. Concentrations of 0.2-5.0 mg/liter of
      the herbicides were used for biodegradation. Two types of river water samples
      with different numbers of microorganisms were collected from the Neris River:
      upstream and downstream of the city of Vilnius. The initial concentration of
      microorganisms varied from 4.7 x 10(5) to 2.7 x 10(6) cells/liter and from 1.4 x
      10(8) to 5.3 x 10(8) cells/liter in water samples from the Neris River upstream
      and downstream of Vilnius, respectively. Chemical analysis was performed by the
      HPLC technique, using standards of herbicides and likely degradation products.
      Chemical parameters of different river water samples used in biodegradation
      experiments were analyzed. A second-order reaction rate model was used for the
      analysis of biodegradation data. Values of the first-order rate constants (Ka)
      revealed the following decrease in the biodegradation rate of herbicides:
      propanil >> diuron > or = monuron = propachlor > fenuron. This sequence was
      constant for all water samples analyzed. The set of decreasing value of second
      order biodegradation rate constants (Kb) differed from the set of first-order
      constants (Ka) because the total number of bacteria in the water samples varied
      by up to two orders of magnitude, and this variation influenced the calculated
      values of Kb. Thus, different sets of Kb values were obtained for the water
      samples from the river upstream and downstream of the city. Schemes of a variety
      of biodegradation models are presented, and the suitability of the second-order
      reaction rate model for the description of biodegradation of xenobiotics is
      discussed.

PMID- 9626532
TI  - Interactions and biodegradation of the herbicide metolachlor with different
      surfaces.
AB  - Degradation of the herbicide metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N
      (2-methoxy-1-methylethyl) acetamide] was used as a model compound to study
      degradation in aqueous media with different biofilm carriers. Biofilm carriers
      used were naturally occurring minerals (NOMI), activated carbons (AC), and
      synthetic minerals combined with activated carbon (MIAC). No transformation was
      found without biofilm carriers or with NOMI as carriers. Degradation with AC was
      accompanied by consumption of oxygen but not by release of chloride. On MIAC
      carriers, release of chloride was observed. Results indicate that abiotic
      mechanisms play a major role in this type of degradation, which can be the basis
      for the development of a microbial community with the ability to degrade
      metolachlor.

PMID- 9626533
TI  - Chlorophyll a fluorescence: a tool for the investigation of toxic effects in the
      photosynthetic apparatus.
AB  - The effects of environmental pollutants, such as triazines, urea herbicides,
      phenols, nitro aromatic compounds, aldehydes, hydrogen sulfide, volatile
      halogenated aliphatic and aromatic compounds, and alkylbenzenes, the
      photosynthesis of green algae were investigated by using detailed analysis of
      chlorophyll a fluorescence. Application of quenching analysis by means of a pulse
      amplitude-modulated fluorometer allows the discrimination of different modes of
      action. Blocks of the electron-transport chain, the action of uncouplers, and
      fluorescence quenching by nitroaormatic compounds could be distinguished.
      Hydrogen sulfide and short-chain aldehydes seem to react in the same way,
      probably by reaction with components of the electron-transport chain. Nonreactive
      volatile compounds affect chlorophyll fluorescence in a strictly hydrophobicity
      dependent manner. The quenching analysis suggests an inhibition of utilization of
      proton-motive force for ATP synthesis. Detailed analysis of fluorescence patterns
      may be of great help for identification of toxic pollutants and their sources.

PMID- 9626534
TI  - Response of two populations of holm oak (Quercus rotundifolia Lam.) to sulfur
      dioxide.
AB  - Experiments were carried out with seedlings of Quercus rotundifolia Lam., an
      evergreen schlerophyllous tree typical of the Spanish Mediterranean climate
      environments. Fruits were collected in two distant (800 km) populations located
      in the center (southern Spain) and northern border (northern Spain) of the area
      of distribution of the species. One-month-old potted plants were grown for 130
      days in an enriched atmosphere of SO2 (0.23 ppm, 14 h/day) in controlled (growth
      chamber) conditions. Both northern and southern plants underwent a significant
      decrease in growth rate as a consequence of the treatment. Even so, plants appear
      to be quite resistant to SO2 compared with either more temperate or more
      productive species. The southern population was more sensitive to the treatment,
      as reflected by the bigger decrease in both growth and photosynthetic rates.
      Differences in resistance appear to be related to the biogeographic origin of the
      populations studied, which underlines the importance of biogeographic aspects in
      studies of resistance to air pollutants.

PMID- 9626535
TI  - Functional enzymes activity and gill histology of carp after copper sulfate
      exposure and recovery.
AB  - Copper sulfate is one of the most widely used algicides for the control of
      phytoplankton in lakes, reservoirs, and ponds. It is also used for aquatic weed
      control. To study the toxic effects of copper on carp (Cyprinus carpio L.),
      toxicity tests were carried out. Fish recovery in copper-free water was followed.
      After a 14-day period of exposure to five concentrations of copper sulfate (0.25
      4.0 mg/L CuSO4, values ranging from approximately 5 to 70% of the 96-h LC-50) and
      a recovery period of the same duration, activities of the functional enzymes
      alkaline phosphatase (AP), aspartate aminotransferase (AST), and alanine
      aminotransferase (ALT) in the blood serum and gills were determined. Because the
      gills are the known target organ for copper, changes in gill structure were
      investigated as well. In all exposure groups for all the enzymes studied, an
      increase in activity was noted after 14 days. The increase in AP activity was the
      most pronounced in both gills and serum of carp exposed to the highest
      concentration tested (4 mg/L). After a "recovery" period, compared with the end
      of treatment, a decrease in enzyme activities was recorded, indicating eventual
      recovery from the Cu-induced stress (the only exception being the ALT activity in
      gills in the highest CuSO4 concentration). The results of biochemical analysis
      were confirmed by histopathology. Lesions such as epithelial hyperplasia, curling
      of secondary lamellae, and changes in chloride cells were observed on the gills,
      and their severity increased with increased toxicant concentration. Most of the
      changes were reversible, as exhibited by gill histopathology after the recovery
      period.

PMID- 9626536
TI  - Characterization of RTG-2 fish cell line by random amplified polymorphic DNA.
AB  - The increasing presence of genotoxic chemicals in the aquatic environment has led
      to the development of both in vivo and in vitro assays for target species. The
      fish population represents an important level of aquatic ecosystems that can be
      threatened by increased environmental pollution. The authors have studied the DNA
      pattern of the RTG-2 fish cell line, a fibroblast-like cell line, derived from
      rainbow trout (Oncorhynchus mikyss), to use this cell line as an in vitro system
      to study genotoxicity by means of random amplified polymorphic DNA primers
      (RAPDs). A constant pattern in the DNA band is essential when an organism or cell
      line is used to detect DNA alterations produced by genotoxic environmental
      chemicals. DNA fingerprints with RAPDs were obtained for RTG-2 by testing 26
      single and 70 pairwise combinations of primers. Different methods of DNA
      extraction (chelating resin, salting out, and phenolization), the influence of
      spectrometric measures at 320 nm in the 260/280 quotient to quantify DNA
      extracts, genomic DNA and primer concentrations, annealing temperatures, and cell
      line passage were studied in the cell line characterization. RAPD products were
      identified by agarose gel electrophoresis. The good results obtained should allow
      the use of this system as a possible tool for detection of the genotoxicity of
      aquatic pollutants.

PMID- 9626537
TI  - The use of biomarkers to measure the interactive effects of chemicals.
AB  - Biomarker assays that provide measures of the toxic effects of chemicals on key
      organisms are of particular interest in ecotoxicology and environmental risk
      assessment. Typically, such assays provide measures of the molecular mechanisms
      that underlie toxicity (e.g., inhibition of brain acetylcholinesterase activity
      by organophosphorus insecticides and retardation of the vitamin K cycle by
      anticoagulant rodenticides). They are particularly valuable for detecting and
      quantifying toxicity where organisms are exposed to mixtures of compounds and for
      identifying cases of potentiation. In birds, inhibition of brain
      acetylcholinesterase activity can provide an index of potentiation of
      organophosphorus and carbamate insecticides by other pesticides. Inhibition of
      serum butyrylcholinesterase also is very useful as a nondestructive assay but is
      not simply related to inhibition of brain acetylcholinesterase. Assays for DNA
      damage can indicate where there is an increase in the rate of activation of
      carcinogens and mutagens due to induction of the cytochrome P450 system. Assays
      for blood levels of retinol (vitamin A) and thyroxine can establish thyroxine
      antagonism by metabolites of 3,3,4,4-tetrachlorobiphenyl. Assays for changes in
      levels of clotting protein in serum can give an indication of the effect of
      mixtures of anticoagulant rodenticides on the vitamin K cycle. The interactive
      effects of mixtures of pesticides in the field are starting to be investigated by
      this approach (e.g., a recent study of the combined action of malathion and
      prochloraz in the red-legged partridge).

PMID- 9626538
TI  - Induction of liver EROD and erythrocytic nuclear abnormalities by
      cyclophosphamide and PAHs in Anguilla anguilla L.
AB  - The induction of liver ethoxyresorufin O-deethylase (EROD) activity and
      erythrocytic nuclear abnormalities (NA) after treatment with two different
      polycyclic aromatic hydrocarbons (PAHs) and cyclophosphamide (CP) was
      investigated in the eel Anguilla anguilla L. EROD activity significantly
      increases either 3 days after one single i.p. injection or 6 days after two i.p.
      injections (on days 0 and 3) of 4 mg/kg beta-naphthoflavone (BNF). EROD activity
      was determined after different lengths of exposure to 4 mg/kg BNF (i.p.
      injection). The results indicated significant increases from 8-h to 12-day
      exposure, with a maximum increase at 4 days and a decline between 4 and 12 days.
      The induction of liver EROD activity and erythrocytic NA was studied, 3 days
      after one 14.7-mumol/kg treatment (i.p. injection) with BNF, benzo[a]pyrene
      (BaP), and CP, in three three different groups of eels. The EROD activity
      significantly increases after BNF and BaP treatment, whereas the erythrocytic NA
      frequency was kept constant; however, CP induces a significant increase in the
      erythrocytic NA frequency, but it does not induce a significant increase in liver
      EROD activity. The sensitivity of A. anguilla liver EROD assay was assessed 3
      days after one i.p. injection of BNF (0.0, 0.03, 0.06, 0.125, 0.25, 0.5, 1.0,
      2.0, and 4.0 mg/kg). This species exhibits a dose response to BNF at the
      concentration range 0-4 mg/kg. The NOEL is between 0.125 and 0.25 mg/kg. The eels
      3-day exposure to water containing BNF (0.0, 0.1, 0.3, 0.9, and 2.7 microM)
      induced a significant increase in liver EROD activity, specifically in
      concentrations of 0.9 and 2.7 microM. The NOEC for the eels external exposure to
      BNF is between 0.3 and 0.9 microM.

PMID- 9626539
TI  - Adaptations and resistance of zooplankton to stress: effects of genetic,
      environmental, and physiological factors.
AB  - The ability of a species to adapt to stress factors such as exposure to toxicants
      depends to a large extent on the presence of individuals that are able to respond
      to the exposure in a successful way. Several strategies can be employed to cope
      with different stress factors. Investments on growth and reproduction, for
      instance, can be varied to meet the requirements of the environment. Large
      individuals generally have a high resistance against stress, but a large body
      size is often achieved at the cost of other characteristics. In the present
      study, the resistance of several clones of Daphnia to different stress factors,
      such as toxic cyanobacteria, a predator released chemical, and starvation, was
      investigated. The focus was on interactions among different factors and whether
      observed responses can be regarded as evolved adaptations for the different
      conditions.

PMID- 9626540
TI  - Acute marine sediment toxicity: a potential new test with the amphipod Gammarus
      locusta.
AB  - Although amphipod toxicity tests have been successfully used in the United States
      to assess coastal sediment toxicity, few tests have been developed with European
      species. The authors have been working with the amphipod Gammarus locusta, a
      widely spread species along European coastal areas that is particularly abundant
      in the Portuguese Sado estuary. This amphipod fulfills the most important
      requirements of a test species. It can be easily reproduced in laboratory and it
      is tolerant to a broad range of sediment types. A series of tests demonstrated
      its sensitivity to copper and gamma-hexachlorocyclohexane (lindane) in the
      sediment (LC50 = 6.8 mg Cu/dry kg, 0.9% total volatile solids; LC50 = 60.5
      micrograms HCH/dry kg, 2% total volatile solids) and to some heavily contaminated
      field sediments. After assessment of the species sensitivity to several
      noncontaminant variables, an experimental protocol was designed to conduct acute
      sediment toxicity tests that are briefly described. Proposed is a 10-day static
      toxicity test at 15 degrees C and 33-34/1000 salinity, with laboratory-produced
      juveniles and mortality as the endpoint. General assay performance is identical
      to the American Society for Testing and Materials (ASTM) standard for sediment
      toxicity tests with marine and estuarine amphipods. The results previously
      obtained revealed a strong potential for this amphipod to be used in
      toxicological testing. Considering the wide geographic distribution of this
      species and its amenability for culturing, it may be an alternative or
      complementary test for ecotoxicological studies in other European coastal systems
      where the existing tests cannot be applied or do not offer a definitive solution.

PMID- 9626541
TI  - Assessing the environmental impact of wastewaters.
AB  - The conventional approach for assessing the environmental impact of wastewaters
      uses a set of global physicochemical and ecotoxicological parameters and is well
      adapted to the vast majority of wastewaters. When some chemicals may be
      particularly harmful for the environment, a specific approach based on a
      comparison between the predicted environmental concentration (PEC) and the
      predicted no-effect concentration (PNEC) may be used. The four steps of
      extrapolation required for PNEC evaluation are discussed and the importance of
      the interspecies extrapolation is highlighted. It may also be useful to use an
      integrated approach relating the characteristics of the wastewater to that of
      specific compounds. For physicochemical parameters, a simple addition is
      adequate, whereas, for ecotoxicity, the problem is more complex. The toxicity of
      a mixture of compounds acting by the same mechanism is often described by the
      concentration addition model. Although this model is very useful for practical
      applications owing to its simplicity, a statistical evaluation of its performance
      indicates that it slightly over-predicts the toxicity of mixtures. A new model
      derived from the statistically sound "independence action" principle and based on
      a precise mathematical description of the dose-response relationship is proposed.
      Applications of this model to mixtures tested with algae demonstrate the accuracy
      of this model with the experimental data.

PMID- 9626542
TI  - Selection of a pesticide with low environmental impact.
AB  - The conditions were analyzed for evaluation of a mean soil biodegradation of a
      pesticide within a certain region. Different soils from two Czech and two German
      regions were used for a highly sensitive analysis based on a laboratory
      incubation of each isolated active soil strain with a radiolabeled pesticide. It
      was proved for all analyzed soils that the biodegradation activity of the total
      biomass was caused by only a small part of the present microbial strains. Not
      only bacteria, but also fungi and yeast have to be taken into consideration in a
      pesticide biodegradation. The biodegradation products were quantified by radio
      high-performance liquid chromatography.

PMID- 9626543
TI  - Recent trends and developments in the EU in the environmental control and
      management of chemicals.
AB  - In the further development and implementation of European legislation on
      chemicals and related products the following aspects and trends can be
      identified: (1) refinement and adaptation of existing legislation and guidelines
      to technical progress (including extension of testing and risk assessment
      strategies), (2) preparation and implementation of new directives and
      regulations, (3) increasing application and further development of screening
      methods and model approaches, and (4) global harmonization of hazard and risk
      assessment criteria and procedures in the frame of the International Forum on
      Chemical Safety (chapter 19 of Agenda 21). The increasing use of evaluation and
      screening models can be illustrated by the further development and application of
      specific models such as EUSES and EASE to predict effect and exposure data. On
      the effects assessment side, models are available or under development to predict
      the phototoxicity and potential endocrine disruptors (estrogen/androgen binding
      affinity) of industrial chemicals. Finally, the emphasis that is given worldwide
      to the global harmonization procedures initiated under chapter 19 of Agenda 21,
      agreed at the UNCED conference for the environment and sustainable development in
      1992, cannot fail to influence further developments in Europe.

PMID- 9626544
TI  - Development of a field bioassay for the side effects of pesticides on
      decomposition.
AB  - A method has been developed for assessing the side effects of fungicides on
      decomposition using litterbags. Twenty dried leaf disks of Chinese cabbage,
      Brassica oleracea, were placed in litterbags (20 x 20 cm) made of nylon fabric
      (25 microns mesh). The litterbags were laid in a treated plot and 5, 10, 20, and
      > 200 m from the treated plot and covered with 1 cm of standard soil. After 1
      week, the dry weight of the leaf disks was determined. In an iterative procedure
      the method was optimized and significant differences of 5% in decomposition rate
      between litterbags were found using the final method presented here. In and
      around agriculturally managed plots, negative effects on decomposition of two
      fungicides could be traced. Effects on decomposition were found after application
      of captan (in fruit, 1.5 kg a.i./ha) and maneb (in potatoes, 3 kg a.i./ha) up to
      10 m from the treated plot, at moderate wind speeds (3-5 m/s). In one case the
      concentration of captan in the soil covering the litterbags was measured. A
      negative correlation was established between captan concentration and
      decomposition. These experiments were repeated in an experimental plot under more
      controlled conditions with respect to the amount and time of application. The
      results of the field experiments could not be reproduced on the experimental
      plot. Additional experiments with soil fungi in agar again demonstrated a
      significant effect of exposure to captan, however. Given the results, the method
      using litterbags requires further development before a standard field trial can
      be designed. Given the knowledge gained with respect to the key factors involved,
      a bioassay using soil fungi seems to have high potential, however.

PMID- 9626545
TI  - Microbiotesting: an expanding field in aquatic toxicology.
AB  - In terms of bioanalytical development and application, environmental evolution in
      this century can be perceived as having gone from the "dark ages" (time period
      preceding the 1960s and essentially characterized by nonuse of bioassays), to the
      "beginning of enlightenment" (use of fish bioassays during the 1960s as screening
      tools for effluents and specific chemicals), to the "regulatory 1970s," when
      newly created environment departments in developed countries began to sanction
      bioassays for regulatory purposes, to the "ecotoxicological 1980s," when suites
      of (micro) bioassays were incorporated in various hazard assessment schemes,
      right up to the present "microbiotesting 1990s," when an unprecedented upsurge in
      development and demand for cost-effective multilevel small-scale assays is
      manifest. This paper offers the view that microscale aquatic toxicology is a
      rapidly expanding field of ecotoxicology involving numerous bioanalytical
      techniques developed and applied at various levels of biological organization.
      This is demonstrated by recalling some of the major highlights that triggered the
      way for increased use of microbiotesting over the past decades. It is expected
      that the field of microbiotesting will sustain continuing growth in the future
      and contribute significant diagnostic power to environmental programs requiring
      ecotoxicology.

PMID- 9626546
TI  - Brown trout as biomonitor of heavy metal pollution: effect of age on the
      reliability of the assessment.
AB  - Brown trout (Salmo trutta L.) is a native fish of the rivers of northern Spain.
      It is the dominant fish species in these rivers, and it is widespread over all
      the range of freshwater ecosystems in the area, including ecosystems potentially
      polluted with heavy metals. In this study, the potential of brown trout as
      biomonitor of heavy metal pollution and the effect of fish age on the reliability
      of the assessment are analyzed. Copper, lead, and cadmium concentrations of both
      abiotic compartments (water and sediments) and brown trout (S. trutta) from three
      northern Spanish rivers were analyzed. Significant correlations were found
      between sediment lead content and lead concentration in trout liver. One-year-old
      juvenile trouts were demonstrated to be useful as a biomonitor of copper and lead
      pollution, revealing between-location differences. Older trouts do not seem
      adequate to properly monitor heavy metal pollution. The effect of aging on the
      reliability of this species as biomonitor is discussed.

PMID- 9626547
TI  - Correlation between on-line PAH detection in airborne particle samples and their
      bacterial genotoxicity.
AB  - The photoelectric aerosol sensor (PAS) is a technique suitable for on-line
      monitoring of particle-bound polycyclic aromatic hydrocarbons (PPAHs). Although
      this is a very fast and inexpensive technique, it does not measure individual PAH
      species but gives a measure of the total amount of PPAHs. Because of the
      suitability of this sensor for air-pollution screening, it is desirable to know
      whether a correlation exists between the PPAHs detected with this method and the
      biological relevance of the respective particle samples. To test the DNA damaging
      potential of the organic fraction of collected particles, the umuC test with
      Salmonella typhimurium TA1535/pSK1002 was used. The primary source for particle
      sampling was a stationary diesel engine, but samples from a parking garage and
      two locations in the city of Zurich have also been included. The total mass of
      PPAHs as determined by the PAS was plotted against the induced genotoxicity. This
      resulted in a linear correlation (r2 = 0.82), indicating that the PAS detects
      biologically relevant PPAHs.

PMID- 9626548
TI  - Laboratory and field-caging studies on hepatic enzymatic activities in European
      eel and rainbow trout.
AB  - Caging field experiments were conducted on young European eel (Anguilla anguilla)
      and on rainbow trout (Onchorynchus mykiss) for the determination of a
      biomonitoring protocol of freshwater streams. Hepatic monooxygenase and
      conjugation enzyme activities were measured as biomarkers of exposure to some
      organic pollutants. Laboratory studies were performed to compare the
      responsiveness of these two species concerning their enzymatic activities. The
      induction of monooxygenase activity, measured as the deethylation of 7
      ethoxyresorufin (EROD activity) was examined by beta-naphtoflavone (beta-NF)
      treatment. Dose-response study revealed that EROD activity increased
      significantly from 1 mg beta-NF/kg bw and was on a plateau at 50 mg beta-NF/kg bw
      for both species. No significant effect on glutathione S-transferase (GST)
      activity was observed. During a time-course study, EROD activity increased,
      starting from the second day for both species. In European eel, this enzymatic
      activity decreased significantly from the seventh day, whereas no significant
      decrease was observed for rainbow trout after 14 days. During a 2-week field
      study, EROD and GST activities were measured in fish held in cages upstream and
      downstream of a polluted area. For both species, the induction of EROD activity
      was observed in the polluted site after 14 days of caging; GST activity was not
      significantly affected. Monooxygenase activity appeared to be a sensitive tool
      for biomonitoring freshwater streams for both species.

PMID- 9626549
TI  - Statistical analysis of cyprinid ethoxyresorufin-O-deethylase data in a large
      French watershed.
AB  - A comparison of ethoxyresorufin-O-deethylase (EROD) data collected in 1995 in
      various sites in the Rhone watershed (France) was carried out to quantify the
      influence of factors such as contamination and biological parameters on EROD
      levels and within-group variabilities. Three species of cyprinids were collected
      and fish chemical contamination was measured. A log transformation of EROD data
      provided both normalization and homogeneity of variances. The influence of female
      sexual maturation on the variability and EROD dimorphism was quantified. A
      relationship with contaminant bioaccumulation was observed. A comparison with
      EROD data collected during previous studies by the same laboratory was made to
      validate the results.

PMID- 9626550
TI  - Impact of wastewater treatment plant discharge on enzyme activity in freshwater
      sediments.
AB  - The biological self-purification processes are a central point for the ecological
      states of rivers. The degradation efficiency of pollutants is mainly due to the
      microflora and can be detected with enzyme-activity tests. Extracellular-enzyme
      activity of freshwater sediments was measured, in a microcosm, versus different
      pollution levels caused by organic wastewater treatment plant (WTP) discharges.
      Biochemical evaluation of Vmax values for each exoenzyme appears to be a function
      of the organic matter content of the WTP effluent (Fig. 2). Glucosidase and
      peptidase reveal a significant negative correlation (respectively, r = 0.99, with
      P < 0.02; and r = 0.853, with P < 0.08) of Vmax versus DOC concentration (i.e.,
      an inhibition effect). The same relationships were observed with K(m) values,
      beta-Glucosidase and aminopeptidase activity are well described by the Michaelis
      Menten equation, but linearization with the Lineweaver-Burk equation does not fit
      with a simple type of inhibition. Two sediments (sand and silt) have been tested,
      and the differences in the exoenzyme activity of the two sediments after WTP
      effluent input could be explained by their physicochemical differences. The
      effects of WTP effluents on a freshwater sediment indicate that, in the current
      experiments, the microbial potential exoenzyme activity does not increase: this
      finding implies that, in rivers, the global hydrolytic potential could remain
      steady down-stream of a discharge point.

PMID- 9626551
TI  - Cytoskeleton alterations by tributyltin (TBT) in tunicate phagocytes.
AB  - The effects of tributyltin chloride (TBT) on cytoskeletal components, as possible
      cell targets of toxicity, were examined on cultured hemocytes of the colonial
      ascidian Botryllus schlosseri by means of indirect immunofluorescence. The
      immunotoxic effect of 10 microM TBT (sublethal concentration) consists of (1)
      inhibition of yeast phagocytosis, Ca2+ ATPase activity, and respiratory burst;
      (2) increase in intracellular Ca2+ concentration; and (3) alterations in cell
      morphology. After 60 min, TBT-exposed amebocytes become spherical, withdrawing
      their long pseudopodia, and lose motility. Their microfilaments assemble in
      clusters around the peripheric cytoplasm, indicating massive disassembly, with
      the exception of unaltered adhesion plaques. Analogously, their microtubules
      reveal extensive disaggregation, being scattered in the cytoplasm and not
      recognizable as single filaments, whereas the microtubule organizing center
      (MTOC) is still visible. Treatment together with 20 micrograms/ml calmodulin
      (CaM) can partially restore the cytoskeleton architecture. These results suggest
      a relationship between TBT and Ca2+ homeostasis in ascidian hemocytes. By
      interfering with Ca2+ ATPase activity through CaM inhibition, either directly or
      indirectly, TBT induces an excess of intracellular Ca2+ accumulation, which first
      causes internal disorganization of cytoskeletal proteins and consequently
      inhibition of phagocytosis, beginning from chemotaxis and particle adhesion.

PMID- 9626552
TI  - Ion regulation in whitefish (Coregonus lavaretus L.) yolk-sac fry exposed to low
      pH and aluminum at low and moderate ionic strength.
AB  - Anadromous whitefish [Coregonus lavaretus (L.)] were exposed during the yolk-sac
      phase to combinations of pH values of 6.0, 5.5, 5.0, 4.5, and 4.0 and nominal Al
      concentrations of 0, 100, 200, and 400 micrograms liter-1 for 4 days. The test
      waters were: (1) lake water diluted 1:1 with ion exchanged water (DLW) and (2)
      artificial water (AW). The major differences were: [Ca2+] 0.069 mmol liter-1 in
      DLW versus 0.034 mmol liter-1 in AW, [Na+] 1.5 and [Cl-] 1.8 times higher in DLW,
      with no dissolved organic material in AW. The fry were sampled daily for the
      analysis of exchangeable body Na+ and Cl- contents, and the swimming activity and
      mortality were registered. Aluminum initially protected yolk-sac fry against
      acidic water at pH 4.0 both in DLW and in AW. Generally, however, an increase in
      [Al] and a decrease in pH increased the adverse effects, seen as decreased
      exchangeable body Na+ and Cl- content, decreased swimming activity, and increased
      mortality. The effects of Al were more pronounced in AW compared with DLW. In AW,
      the Na+ and Cl- content of the fry already decreased after 1 day of exposure to a
      level that predicts mortalities. There was a time trend in DLW toward decreasing
      exchangeable body Na+ and Cl- concentrations as a function of increasing acidity
      and [Al]. In DLW, mortalities occurred primarily at pH 4.0; at that pH value in
      AW, the mortality rate was even higher, and mortalities also occurred after 2 to
      4 days at all other pH values. There was a threshold limit in exchangeable body
      Na+ and Cl- concentrations at which yolk-sac fry became passive; it was at
      approximately 0.3 mumol per fry in DLW and was slightly higher in AW. In the DLW
      control with moderate ionic strength, the Na+/Cl- ratio was above 1 from the
      second exposure day on but remained closer to 1 in soft AW control. The Na+/Cl-
      ratio was predominantly > 1 in AW when the fry were exposed to moderate acidities
      but approached 1 at pH values < 5.0. The Na+/Cl- ratio was mostly < or = 1 in
      DLW, irrespective of the exposure, indicating cation selectivity of ion leakage
      pathways in slightly harder water.

PMID- 9626553
TI  - Assessment of the ecotoxic potential of soil contaminants by using a soil-algae
      test.
AB  - To assess the ecotoxic potential of soil contaminants, a test with the soil alga
      Chlorococcum infusionum has been developed, enabling investigations of soil
      pollutions with soluble and fairly soluble chemicals. Three soil types
      artificially contaminated with Sb compounds and five soils from a historical
      mining area, which were highly polluted with Sb, As, Hg, and Cu, were used as
      test soils. For antimony, EC50 values from 125 mg/kg up to > 1000 mg/kg,
      depending on soil type, were determined. Two of five soils from the mining area
      caused toxic effects. Additionally, aqueous extracts of all soils were exposed in
      established tests (daphnid, alga, bacterium). In contrast with the soil-algae
      test, no toxic effects were found. Aquatic tests with SbO/K tartrate were
      performed to point out the toxicity of antimony. The following EC50 values in
      milligrams of Sb per liter were determined: Scenedesmus subspicatus, 59 mg/liter;
      Chlorococcum infusionum, 43 mg/liter; Daphnia magna, 8 mg/liter; and Vibrio
      fisheri, 7 mg/liter.

PMID- 9626554
TI  - Prolactin (PRL) and its receptor: actions, signal transduction pathways and
      phenotypes observed in PRL receptor knockout mice.
AB  - PRL is an anterior pituitary hormone that, along with GH and PLs, forms a family
      of hormones that probably resulted from the duplication of an ancestral gene. The
      PRLR is also a member of a larger family, known as the cytokine class-1 receptor
      superfamily, which currently has more than 20 different members. PRLRs or binding
      sites are widely distributed throughout the body. In fact, it is difficult to
      find a tissue that does not express any PRLR mRNA or protein. In agreement with
      this wide distribution of receptors is the fact that now more than 300 separate
      actions of PRL have been reported in various vertebrates, including effects on
      water and salt balance, growth and development, endocrinology and metabolism,
      brain and behavior, reproduction, and immune regulation and protection. Clearly,
      a large proportion of these actions are directly or indirectly associated with
      the process of reproduction, including many behavioral effects. PRL is also
      becoming well known as an important regulator of immune function. A number of
      disease states, including the growth of different forms of cancer as well as
      various autoimmune diseases, appear to be related to an overproduction of PRL,
      which may act in an endocrine, autocrine, or paracrine manner, or via an
      increased sensitivity to the hormone. The first step in the mechanism of action
      of PRL is the binding to a cell surface receptor. The ligand binds in a two-step
      process in which site 1 on PRL binds to one receptor molecule, after which a
      second receptor molecule binds to site 2 on the hormone, forming a homodimer
      consisting of one molecule of PRL and two molecules of receptor. The PRLR
      contains no intrinsic tyrosine kinase cytoplasmic domain but associates with a
      cytoplasmic tyrosine kinase, JAK2. Dimerization of the receptor induces tyrosine
      phosphorylation and activation of the JAK kinase followed by phosphorylation of
      the receptor. Other receptor-associated kinases of the Src family have also been
      shown to be activated by PRL. One major pathway of signaling involves
      phosphorylation of cytoplasmic State proteins, which themselves dimerize and
      translocate to nucleus and bind to specific promoter elements on PRL-responsive
      genes. In addition, the Ras/Raf/MAP kinase pathway is also activated by PRL and
      may be involved in the proliferative effects of the hormone. Finally, a number of
      other potential mediators have been identified, including IRS-1, PI-3 kinase, SHP
      2, PLC gamma, PKC, and intracellular Ca2+. The technique of gene targeting in
      mice has been used to develop the first experimental model in which the effect of
      the complete absence of any lactogen or PRL-mediated effects can be studied.
      Heterozygous (+/-) females show almost complete failure to lactate after the
      first, but not subsequent, pregnancies. Homozygous (-/-) females are infertile
      due to multiple reproductive abnormalities, including ovulation of premeiotic
      oocytes, reduced fertilization of oocytes, reduced preimplantation oocyte
      development, lack of embryo implantation, and the absence of pseudopregnancy.
      Twenty per cent of the homozygous males showed delayed fertility. Other
      phenotypes, including effects on the immune system and bone, are currently being
      examined. It is clear that there are multiple actions associated with PRL. It
      will be important to correlate known effects with local production of PRL to
      differentiate classic endocrine from autocrine/paracrine effects. The fact that
      extrapituitary PRL can, under some circumstances, compensate for pituitary PRL
      raises the interesting possibility that there may be effects of PRL other than
      those originally observed in hypophysectomized rats. The PRLR knockout mouse
      model should be an interesting system by which to look for effects activated only
      by PRL or other lactogenic hormones. On the other hand, many of the effects
      reported in this review may be shared with other hormones, cytokines, or growth
      factors and thus will be more difficult to study. (ABSTRACT TRUNCATED)

PMID- 9626555
TI  - Brain corticosteroid receptor balance in health and disease.
AB  - In this review, we have described the function of MR and GR in hippocampal
      neurons. The balance in actions mediated by the two corticosteroid receptor types
      in these neurons appears critical for neuronal excitability, stress
      responsiveness, and behavioral adaptation. Dysregulation of this MR/GR balance
      brings neurons in a vulnerable state with consequences for regulation of the
      stress response and enhanced vulnerability to disease in genetically predisposed
      individuals. The following specific inferences can be made on the basis of the
      currently available facts. 1. Corticosterone binds with high affinity to MRs
      predominantly localized in limbic brain (hippocampus) and with a 10-fold lower
      affinity to GRs that are widely distributed in brain. MRs are close to saturated
      with low basal concentrations of corticosterone, while high corticosterone
      concentrations during stress occupy both MRs and GRs. 2. The neuronal effects of
      corticosterone, mediated by MRs and GRs, are long-lasting, site-specific, and
      conditional. The action depends on cellular context, which is in part determined
      by other signals that can activate their own transcription factors interacting
      with MR and GR. These interactions provide an impressive diversity and complexity
      to corticosteroid modulation of gene expression. 3. Conditions of predominant MR
      activation, i.e., at the circadian trough at rest, are associated with the
      maintenance of excitability so that steady excitatory inputs to the hippocampal
      CA1 area result in considerable excitatory hippocampal output. By contrast,
      additional GR activation, e.g., after acute stress, generally depresses the CA1
      hippocampal output. A similar effect is seen after adrenalectomy, indicating a U
      shaped dose-response dependency of these cellular responses after the exposure to
      corticosterone. 4. Corticosterone through GR blocks the stress-induced HPA
      activation in hypothalamic CRH neurons and modulates the activity of the
      excitatory and inhibitory neural inputs to these neurons. Limbic (e.g.,
      hippocampal) MRs mediate the effect of corticosterone on the maintenance of basal
      HPA activity and are of relevance for the sensitivity or threshold of the central
      stress response system. How this control occurs is not known, but it probably
      involves a steady excitatory hippocampal output, which regulates a GABA-ergic
      inhibitory tone on PVN neurons. Colocalized hippocampal GRs mediate a
      counteracting (i.e., disinhibitory) influence. Through GRs in ascending aminergic
      pathways, corticosterone potentiates the effect of stressors and arousal on HPA
      activation. The functional interaction between these corticosteroid-responsive
      inputs at the level of the PVN is probably the key to understanding HPA
      dysregulation associated with stress-related brain disorders. 5. Fine-tuning of
      HPA regulation occurs through MR- and GR-mediated effects on the processing of
      information in higher brain structures. Under healthy conditions, hippocampal MRs
      are involved in processes underlying integration of sensory information,
      interpretation of environmental information, and execution of appropriate
      behavioral reactions. Activation of hippocampal GRs facilitates storage of
      information and promotes elimination of inadequate behavioral responses. These
      behavioral effects mediated by MR and GR are linked, but how they influence
      endocrine regulation is not well understood. 6. Dexamethasone preferentially
      targets the pituitary in the blockade of stress-induced HPA activation. The brain
      penetration of this synthetic glucocorticoid is hampered by the mdr1a P
      glycoprotein in the blood-brain barrier. Administration of moderate amounts of
      dexamethasone partially depletes the brain of corticosterone, and this has
      destabilizing consequences for excitability and information processing. 7. The
      set points of HPA regulation and MR/GR balance are genetically programmed, but
      can be reset by early life experiences involving mother-infant interaction. 8.
      (ABSTRACT TRUNCATED)

PMID- 9626556
TI  - Multimodal influence of estrogen upon gonadotropin-releasing hormone neurons.

PMID- 9626557
TI  - Biological esterification of steroids.

PMID- 9626558
TI  - Molecular mechanisms of transforming growth factor-beta signaling.

PMID- 9626559
TI  - Apparent role of hydroxyl radicals in oxidative brain injury induced by sodium
      nitroprusside.
AB  - Sodium nitroprusside (disodium nitroferricyanide) has been suggested to cause
      cytotoxicity through either the release of cyanide and/or nitric oxide. The
      present study investigated a possible mechanism that after a brief release of
      nitric oxide, iron moiety of breakdown products of sodium nitroprusside could
      cause a long lasting oxidative stress, such as hydroxyl radical generation, lipid
      peroxidation and cytotoxicity. Intranigral administration of sodium nitroprusside
      (0-16.8 nmol) to rats induced an acute increase in lipid peroxidation in the
      substantia nigra and a chronic dopamine depletion in the caudate nucleus.
      Photodegraded (nitric oxide-exhausted) sodium nitroprusside, however, still
      produced lipid peroxidation and neurotoxicity in the midbrain. Moreover, non-iron
      containing nitric oxide-donor compounds, such as S-nitroso-N-acetylpenicillamine,
      did not cause oxidative brain injury in vivo suggesting that nitric oxide may not
      mediate neurotoxicity induced by sodium nitroprusside. Additional in vitro
      studies demonstrated that both freshly prepared (nitric oxide donor) and
      photodegraded (nitric oxide-exhausted) sodium nitroprusside generated hydroxyl
      radicals in the presence of ascorbate and also increased lipid peroxidation in
      brain homogenates. These pro-oxidative effects of sodium nitroprusside were
      blocked by nitric oxide, S-nitroso-N-acetylpenicillamine, oxyhemoglobin, and
      deferoxamine (iron chelator). The present results suggest that iron moiety,
      rather than nitric oxide, may mediate the pro-oxidative properties of sodium
      nitroprusside. With this new information in mind, the misuse of sodium
      nitroprusside as a selective nitric oxide donor in both basic and clinical uses
      should be urgently addressed.

PMID- 9626560
TI  - Electronic spin resonance detection of superoxide and hydroxyl radicals during
      the reductive metabolism of drugs by rat brain preparations and isolated cerebral
      microvessels.
AB  - A spin trapping technique was used to analyze by electron spin resonance (ESR)
      the formation of oxygen-derived free radicals during the cerebral reductive
      metabolism of xenobiotics able to undergo a single electron reduction, i.e.
      quinones, pyridinium compounds and nitroheterocyclics. Paraquat, menadione and
      nitrofurazone were used as model compounds of these three classes of molecules.
      ESR spectra indicative of superoxide and hydroxyl radical formation were obtained
      by incubation of brain homogenates directly within the ESR cavity at 37 degrees C
      for each of the three molecules tested. These signals were dependent on
      nucleotide cofactors, and increased in a time-dependent manner. The NADPH and
      NADH dependent free radical production was further characterized in brain
      microsomal and mitochondrial fractions, respectively. By using various
      combinations of reactive species inactivating enzymes (superoxide dismutase,
      catalase), a metal chelator (deferoxamine), and an hydroxyl trapping agent
      (dimethylsulfoxide), it was shown that (1) the primary radical generated was the
      superoxide anion; and (2) a significant production of the hydroxyl radical also
      occurred, that was secondary to the superoxide anion production. Consistent
      signals indicative of the production of both oxygen-derived free radicals were
      obtained when isolated cerebral microvessels which constitute the blood-brain
      barrier were incubated with the model molecules. This is of particular
      toxicological relevance, because this barrier represents a key element in the
      protection of the brain, and is in close contact with blood-born exogenous
      molecules.

PMID- 9626561
TI  - Estimation of nitrite ions by the formation of aryl nitroanion radicals in the
      reaction with the aminoarene 3,5-dibromo-4-amino-benzenesulfonic acid by EPR
      spectroscopy. The use of 15N-nitrite as an internal standard.
AB  - The reaction between the aminoarene 3,5-dibromo-4-aminobenzenesulfonic acid (Na
      salt) and nitrite ions gives rise to the corresponding nitroanion radical. In the
      reaction the amino group of the parent substance was replaced by NO2 from the
      nitrite ions. This leads to two different EPR spectra when the reaction was made
      with 14N and 15N nitrite. Furthermore, the two spectra were completely separated
      with no overlaps, a property which was utilised for a quantitative evaluation of
      samples of 14N nitrite by means of the addition of a known amount of 15N nitrite
      as an internal standard. Variation of the concentration of the nitroanion
      radicals was eliminated since the variation will affect the 14N and 15N products
      to the same extent. The amplitudes of the spectral components M1 = +1 of the 14N
      spectrum and M1 = +1/2 of the 15N spectrum were used for the evaluation of the
      14N nitrite content of the sample.

PMID- 9626562
TI  - DNA single strand breaks and adenine nucleotide depletion as indices of oxidant
      effects on human lung cells.
AB  - The comet assay (single cell gel electrophoresis) is a novel method to assess DNA
      strand breaks in single cells. We studied the oxidant sensitivity of cultured
      primary and transformed (MeT-5A) human pleural mesothelial cells, as well as
      primary and transformed (BEAS 2B) human bronchial epithelial cells, and compared
      the results obtained with the Comet assay to other markers of oxidant effects on
      cells, such as depletion of intracellular high-energy nucleotides (ATP, ADP,
      AMP), accumulation of products of nucleotide catabolism (xanthine, hypoxanthine,
      uric acid), and release of lactate dehydrogenase (LDH). The cells were exposed
      for 5 min to 4 h to 50-500 microM H2O2 or to 5-50 microM menadione. Significant
      tail moment increase, which is a marker of DNA strand breaks in the Comet assay,
      and intracellular nucleotide depletion occurred simultaneously in MeT-5A and BEAS
      2B cells during the first 30-60 min of exposure to H2O2 and menadione. In the
      Comet assay variation between the individual cells could be detected. LDH
      release, a marker of cell injury, showed that mesothelial cells were far more
      sensitive than epithelial cells to oxidant-induced lytic cell injury. MeT-5A and
      BEAS 2B cells contained similar intracellular antioxidant enzyme activities,
      which may explain their similar oxidant sensitivity in the Comet assay. A
      significant increase (164%) in the tail moment was detectable in MeT-5A cells
      exposed to 50 microM H2O2 for 30 min. This returned to control level during the 4
      h of continuing exposure. A 30 min exposure of 25 microM menadione caused a 61%
      increase in the mean tail moment but, unlike with H2O2, the change was
      irreversible during the following 4 h incubation. We conclude that human pleural
      mesothelial cells and bronchial epithelial cells show similar oxidant sensitivity
      when assessed by the Comet assay, but various oxidants differ in their potency in
      causing DNA breaks in these cells.

PMID- 9626563
TI  - Localization of extracellular superoxide dismutase in rat lung: neutrophils and
      macrophages as carriers of the enzyme.
AB  - Immunohistochemistry (IHC) and in situ hybridization (ISH) was used to localize
      extracellular superoxide dismutase (EC-SOD) and its mRNA in rat lung before and
      after a lipopolysaccharide (LPS)- and hyperoxia-induced inflammation. In control
      rats, EC-SOD mRNA was synthesized in macrophages and in cells of the arterial
      vessel walls and the alveolar septa. The EC-SOD protein was mainly localized in
      plasma and on the apical side of the epithelial cells located near bronchus
      associated lymphoid tissue (BALT). ISH did not reveal major changes in the
      distribution of EC-SOD mRNA upon induction of inflammation. In contrast, IHC
      demonstrated a progressive staining of the epithelium of the larger bronchi for
      the protein. Neutrophils and macrophages invading the lung showed an intensive
      staining for the EC-SOD protein concomitantly with a decrease of the enzyme in
      the plasma. Twenty-four hours after LPS stimulation only a spotty positivity
      remained on neutrophils in and between the alveolar spaces. In the
      bronchoalveolar lavage fluid (BALF), only macrophages showed a strong positivity
      for EC-SOD mRNA while the protein was detected in macrophages and neutrophils.
      Exposure to hyperoxia did not affect the distribution of EC-SOD mRNA and protein.
      The presented data demonstrated that in lung tissue the EC-SOD enzyme may have a
      protective function for activated macrophages, neutrophils, and lympoid tissue
      associated epithelial cells.

PMID- 9626564
TI  - Blue light-induced singlet oxygen generation by retinal lipofuscin in non-polar
      media.
AB  - Accumulation of lipofuscin (LF) is a prominent feature of aging in the human
      retinal pigment epithelium (RPE) cells. This age pigment exhibits substantial
      photoreactivity, which may increase the risk of retinal photodamage and
      contribute to age-related maculopathy. In a previous study, we detected singlet
      oxygen generation by lipofuscin granules excited with blue light. In this paper
      we investigated the ability of hydrophobic components of lipofuscin to
      photogenerate singlet oxygen in non-polar environments. Singlet oxygen was
      detected directly by monitoring its characteristic phosphorescence at ca 1270 nm.
      The action spectrum of singlet oxygen formation indicated that this process was
      strongly wavelength-dependent and its efficiency decreased with increasing
      wavelength by a factor of ten, comparing 420 nm and 520 nm. The quantum yield of
      singlet oxygen increased with increasing concentration of oxygen. Using laser
      flash photolysis we studied the possible mechanism of singlet oxygen formation.
      The observed transient, with a broad absorption spectrum peaking at around 440
      nm, was identified as a triplet with lifetime ca 11 microseconds. It was quenched
      by both molecular oxygen and beta-carotene with concomitant formation of a beta
      carotene triplet state. These results indicate the potential role of hydrophobic
      components of lipofuscin in blue light-induced damage to the RPE.

PMID- 9626565
TI  - Effects of several agents on UVB- and UVA plus systemic fluoroquinolone-induced
      erythema of guinea pig skin evaluated by reflectance colorimetry.
AB  - The aim of this study was to clarify the mechanisms underlying the erythema of
      guinea pig skin induced by ultraviolet (UV) irradiation alone and in combination
      with a systemic fluoroquinolone (FQ). The effects of several drugs which may
      modify the actions of some inflammatory mediators and radicals possibly released
      in the inflamed site on the erythema were examined and compared in an objective
      and quantitative way by measuring the change in color of the irradiated skin,
      determined as the change in chroma (C*) with use of reflectance colorimetry.
      After confirming that the C* value increased in an irradiation dose-dependent
      manner and reached a plateau 1-2 h after irradiation of UVB alone or UVA
      coadministered with an FQ, Y-26611 (10 mg/kg, i.p.), guinea pigs were pretreated
      with indomethacin, butylated hydroxytoluene (BHT) or beta-carotene before, or
      treated with H1- or H2-receptor antagonist, superoxide dismutase or N omega-nitro
      L- arginine methyl ester after UV irradiation, and their inhibitory effects
      against erythema were evaluated. It was suggested that there are some substantial
      differences between UVB- and UVA plus FQ-induced erythemas. Although histamine
      makes little contribution to both types of erythema, metabolites of arachidonic
      acid catalyzed by cyclooxygenase contribute more to UVB-induced erythema, whereas
      superoxides take more part in UVA plus FQ-induced erythema. Furthermore, nitric
      oxide seems to participate in both types of erythema; however, the pretreatment
      with BHT or beta-carotene was ineffective against both erythemas. From these
      results, interventions should be directed to powerfully scavenging radicals for
      prevention and treatment of UV plus FQ-induced phototoxicity.

PMID- 9626566
TI  - Procyanidins extracted from Pinus maritima (Pycnogenol): scavengers of free
      radical species and modulators of nitrogen monoxide metabolism in activated
      murine RAW 264.7 macrophages.
AB  - Nitrogen monoxide (NO) has diverse physiological roles and also contributes to
      the immune defense against viruses, bacteria, and other parasites. However,
      excess production of NO is associated with various diseases such arthritis,
      diabetes, stroke, septic shock, autoimmune, chronic inflammatory diseases, and
      atheriosclerosis. Cells respond to activating or depressing stimuli by enhancing
      or inhibiting the expression of the enzymatic machinery that produce NO. Thus,
      maintenance of a tight regulation of NO production is important for human health.
      Phytochemicals have been traditionally utilized in ways to treat a family of
      pathologies that have in common the disregulation of NO production. Here we
      report the scavenging activity of Pycnogenol (the polyphenols containing extract
      of the bark from Pinus maritima) against reactive oxygen and nitrogen species,
      and its effects on NO metabolism in the murine macrophages cell line RAW 264.7.
      Macrophages were activated by the bacterial wall components lipopolysaccharide
      (LPS) and interferon (IFN-gamma), which induces the expression of large amounts
      of the enzyme nitric oxide synthase (iNOS). Preincubation of cells with
      physiological concentrations of Pycnogenol significantly decreased NO generation.
      It was found that this effect was due to the combination of several different
      biological activities, i.e., its ROS and NO scavenging activity, inhibition of
      iNOS activity, and inhibition of iNOS-mRNA expression. These data begin to
      provide the basis for the conceptual understanding of the biological activity of
      Pycnogenol and possibly other polyphenolic compounds as therapeutic agents in
      various human disorders.

PMID- 9626567
TI  - Effects of G6PD overexpression in NIH3T3 cells treated with tert-butyl
      hydroperoxide or paraquat.
AB  - The major physiological role of glucose-6-phosphate dehydrogenase (G6PD) is to
      provide NADPH, which is required for reductive biosynthesis and for
      detoxification of free radicals and peroxides in mature red blood cells. To study
      the function of G6PD in non-erythroid cells, we examined the sensitivity of
      NIH3T3 cells transfected with a plasmid containing human G6PD cDNA to tert-butyl
      hydroperoxide (TBH) and paraquat. Two transfected clones which had a sixteen-fold
      (H7 clone) and six-fold (H6 clone) increase in their intracellular G6PD activity
      were compared with control cells transfected with a vector alone. Cells with high
      level expression of human G6PD were 2.3 (H6) to 3.7 (H7) times more resistant to
      TBH than control cells. The antioxidant (anti-TBH) abilities in H6 and H7 cells
      were revealed by (1) a significant increase in the intracellular level of NADPH
      and glutathione, (2) a reduction of fluorescent intensity of the oxidant
      sensitive dye, 2',7'-dichlorofluorescin diacetate, and (3) a significant
      reduction in the production of oxidized adducts generated by lipid peroxidation.
      In contrast, cells overexpressing G6PD were very sensitive to paraquat, a
      superoxide-producing herbicide. The concentrations of paraquat required to
      produce a 50% decrease in cell viability of H7, H6 and control cells were 0.80
      mM, 1.14 mM, and 2.19 mM, respectively. The cytotoxicity of paraquat correlated
      with the expression level of NADPH in the cells. In this study, overexpression of
      human G6PD in NIH3T3 cells had different effects on the toxicity of TBH vs.
      paraquat. Reduction of NADP+ to NADPH by G6PD protects cells from oxidative
      damage by TBH, but appears to enhance the toxicity of paraquat.

PMID- 9626568
TI  - Human low density lipoprotein as a target of hypochlorite generated by
      myeloperoxidase.
AB  - The aim of this study was to further clarify which part of human low density
      lipoprotein (LDL) is attacked by the MPO/H2O2/Cl- -system and which reactive
      oxygen species is responsible for the attack. Therefore the influence of this
      system on the modification of the lipid and protein moiety of LDL was studied in
      vitro. Using the monochlorodimedone assay it was found that HOCl is produced in
      micromolar quantities in the absence of LDL and is rapidly consumed by LDL in a
      concentration dependent manner. The consumption of HOCl was reflected in the
      formation of HOCl-specific epitopes on apo B-100 as determined by an antibody
      raised against HOCl-modified LDL. The absorbency at 234 nm was applied to measure
      continuously the extent of modification of LDL. The general kinetic pattern of
      the absorbency measurement consisted of a lag phase where no LDL modification was
      observed, followed by a rapid increase of absorbency and a plateau phase. Finally
      the absorbency decreased due to LDL precipitation. Time dependent absorption
      spectra indicated that this kinetic pattern is mainly caused by light scattering
      due to particle aggregation rather than by a specific absorption at 234 nm due to
      conjugated diene formation. In agreement with this finding a low rate of
      thiobarbituric acid reactive substances (TBArS) formation was observed after a
      lag phase. The aggregation of LDL occurs most likely by modification of apo B
      100, which was determined fluorimetrically in terms of LDL-tryptophan destruction
      in presence of the MPO/H2O2/Cl(-)-system. The kinetic course of tryptophan
      fluorescence generally consisted of a rapid decrease leveling off into a low
      plateau phase. Gas chromatographic determinations of linoleic acid in LDL in
      presence of the MPO system showed that this polyunsaturated fatty acid (PUFA) is
      easily attacked by HOCl. Consistent with this finding NMR spectra of HOCl
      modified LDL indicated a complete disappearance of bis-allylic methylene groups.
      Since lipid peroxidation products only partially account for this loss of PUFAs,
      other reactions of HOCl with unsaturated lipids--probably chlorohydrin formation-
      must be involved. Summarizing, although the rate of lipid peroxidation is low,
      both the lipid and the protein moiety of LDL are readily modified by the MPO
      system. It appears that the immediate consequence of apo B-100 modification is
      its aggregation. It is concluded that MPO, which has been detected in
      atherosclerotic lesions, is able to contribute to the modification of LDL into a
      form recognizable for uncontrolled uptake by macrophages.

PMID- 9626569
TI  - Spatial learning and memory deficits induced by dopamine administration with
      decreased glutathione.
AB  - Administration of buthionine sulfoximine (BSO) selectively inhibits glutathione
      (GSH) biosynthesis and induces a GSH deficiency. Decreased GSH levels in the
      brain may result in less oxidative stress (OS) protection, because GSH
      contributes substantially to intracellular antioxidant defense. Under these
      conditions, administration of the pro-oxidant, dopamine (DA), which rapidly
      oxidizes to form reactive oxygen species, may increase OS. To test the cognitive
      behavioral consequences of decreased GSH, BSO (3.2 mg in 30 microliters,
      intracerebroventricularly) was administered to male Fischer 344 rats every other
      day for 4 days. In addition, DA (15 microliters of 500 microM) was administered
      every day [either 1 h after BSO (BSO + DA group) or 1 h before BSO (DA + BSO
      group), when given on the same day as BSO] and spatial learning and memory
      assessed (Morris water maze, six trials/day). BSO + DA rats, but not DA + BSO
      rats, demonstrated cognitive impairment compared to a vehicle group, as evidenced
      by increased latencies to find the hidden platform, particularly on the first
      trial each day. Also, the BSO + DA group utilized non-spatial strategies during
      the probe trials (swim with no platform): i.e., less time spent in the platform
      quadrant, fewer crossings and longer latencies to the previous platform location,
      and more time spent in the platform quadrant, fewer crossings and longer
      latencies to the previous platform location, and more time spent around the edge
      of the pool rather than in the platform zone. Therefore, the cognitive behavioral
      consequences of decreasing GSH brain levels with BSO in conjunction with DA
      administration depends on the order of administration. These findings are similar
      to those seen previously on rod and plank walking performance, as well as to
      those seen in aged rats, suggesting that the oxidation of DA coupled with a
      reduced capacity to respond to oxidative stress may be responsible for the
      induction of age-related cognitive deficits.

PMID- 9626570
TI  - Stress proteins and SH-groups in oxidant-induced cellular injury after chronic
      ethanol administration in rat.
AB  - It is generally agreed that lipid peroxides play an important role in the
      pathogenesis of ethanol-induced cellular injury and that free sulfhydryl groups
      are vital in cellular defense against endogenous or exogenous oxidants. It has
      been observed that oxidative stress induces the synthesis of the 70-kDa family of
      heat-shock proteins (HSPs). Induction of HSPs represents an essential and highly
      conserved cellular response to a variety of stressful stimuli. In the present
      study we measured in various brain areas and in liver the intracellular levels of
      HSP70 proteins, sulfhydryl groups and the antioxidant enzyme status after chronic
      administration of mild intoxicating doses of ethanol to rats. Expression of HSP70
      in response to alcohol administration was particularly high in the hippocampus
      and striatum. In these brain areas, the increase in HSP70 protein levels occurred
      in absence of significant changes of antioxidant enzyme activities and was
      correlated with a marked depletion of intracellular bound thiols and with a
      decreased susceptibility to lipid peroxidation. Lower levels of HSP70 induction
      were found in cortex and cerebellum and were associated to decreases in SOD and
      CAT enzyme activities, with a lower depletion of protein bound thiols and with an
      increased susceptibility to lipid peroxidation. This study agrees with our
      previous results performed on acute alcohol intoxication and supports the
      hypothesis that HSP70 induction protects the different brain areas against
      oxidative stress.

PMID- 9626571
TI  - Inhibitory effect of free radicals derived from organic hydroperoxide on
      progesterone synthesis in human term placental mitochondria.
AB  - Different natural and synthetic organic hydroperoxides have been found to
      stimulate TBARS formation in human term placental mitochondria. The levels of
      TBARS were lower than arising from NADPH-dependent lipid peroxidation. BHT, Mn2+
      and DMPO counteracted TBARS formation in the presence of cumene hydroperoxide
      implicating involvement of free radicals in this process. On the other hand
      superoxide dismutase, catalase and EDTA while being inhibitory in NADPH-dependent
      lipid peroxidation did not inhibit cumene hydroperoxide-dependent TBARS
      formation. Amphenone B and SKF-525A, inhibitors of cytochrome P-450, strongly
      inhibit both NADPH- and cumene hydroperoxide-dependent lipid peroxidation. These
      data provide evidence that cytochrome P-450SCC is involved in both these
      processes. However NADPH-dependent lipid peroxidation and the cumene
      hydroperoxide have been found to inactivate placental mitochondrial cytochrome P
      450SCC. The presence of cumene hydroperoxide resulted in a more rapid
      inactivation of cytochrome P-450SCC and consequently inhibited NADPH-dependent
      lipid peroxidation. It has been observed for the first time that progesterone
      biosynthesis can be inhibited by cumene hydroperoxide. Protective effect of Mn2+
      and DMPO on progesterone biosynthesis indicates the importance of free radicals
      as transient products of cytochrome P-450SCC-dependent cumene hydroperoxide
      metabolism. In contrast to progesterone formation from cholesterol, the
      conversion of pregnenolone to progesterone was not affected by cumene
      hydroperoxide. This suggests that inhibition of progesterone synthesis from
      cholesterol by hydroperoxide may be ascribed to its effect on the desmolase
      activity of cytochrome P-450SCC in placental mitochondria. On the basis of the
      results obtained, we propose that the inhibition of progesterone biosynthesis by
      naturally occurring hydroperoxides may contribute to the development of
      preeclampsia.

PMID- 9626572
TI  - Measurements of plasma glutaredoxin and thioredoxin in healthy volunteers and
      during open-heart surgery.
AB  - Thioredoxin (Trx) and glutaredoxin (Grx) are both multifunctional redox-active
      proteins. In this study, Grx was identified in human plasma by immunoaffinity
      purification. The affinity-purified material from human plasma displayed a band
      of 12 kDa identical to recombinant human Grx by Western blotting and its
      glutathione-dependent reducing activity of beta-hydroxyethyl disulfide.
      Competitive enzyme-linked immunosorbent assays (ELISA) showed that plasma levels
      (mean +/- SD) of Grx and Trx in healthy volunteers (n = 41) were 456 +/- 284
      ng/ml and 28.5 +/- 12.6 ng/ml, respectively. In cardiac surgical patients (n =
      17), plasma Grx levels did not significantly change during cardiopulmonary bypass
      (CPB). In contrast, Trx levels in arterial plasma measured by sandwich ELISA and
      corrected for hemolysis were elevated during reperfusion of the postcardioplegic
      heart (p = .0001 at maximum), whereas by competitive ELISA Trx increased during
      surgical preparation for CPB, but decreased during CPB. When recombinant Trx was
      oxidized, immunoreactive Trx levels were decreased by competitive ELISA but not
      changed by sandwich ELISA. These results suggest that oxidized Trx is released
      into plasma during CPB. There was no significant difference in Trx and Grx levels
      between arterial and intracoronarial plasma samples, indicating no specific
      release by the post-cardioplegic heart. Trx and Grx may be important components
      in the plasma defense against oxidative stress.

PMID- 9626573
TI  - Vitamin E consumption induced by oxidative stress in red blood cells is enhanced
      by melatonin and reduced by N-acetylserotonin.
AB  - The effect of melatonin and its precursor N-acetylserotonin was studied in a
      model of lipid peroxidation induced in human red blood cells by incubation with
      cumene hydroperoxide (CHP) and H2O2. The oxidative stress was expressed as
      vitamin E consumption in the presence of melatonin or N-acetylserotonin
      (concentration ranging from 0.3 to 400 microM): incubation with melatonin not
      only lacked any protective effect but it induced a dose-dependent extra vitamin E
      consumption with both CHP and H2O2. On the contrary, N-acetylserotonin showed a
      strong antioxidant effect at concentrations between 100 and 400 microM. The
      hydrogen-donating capacity of melatonin and N-acetylserotonin was also evaluated
      from the decay of the ESR signal of galvinoxyl radical used as hydrogen
      abstractor. Lack of hydrogen-donating capacity was observed with melatonin,
      whereas N-acetylserotonin showed a significant hydrogendonating capacity although
      inferior to vitamin E, thus suggesting that N-acetylserotonin acts by the
      classical antioxidant mechanism of hydrogen donation. The measurement of the
      oxidation potential and the specific molecular structure suggest that the vitamin
      E consumption effect observed with melatonin could be due to the interactions of
      its radical cation or derivatives on vitamin E.

PMID- 9626574
TI  - Mechanism of regulation of 8-hydroxyguanine endonuclease by oxidative stress:
      roles of FNR, ArcA, and Fur.
AB  - We found previously that 8-hydroxyguanine (oh8Gua) endonuclease in E. coli is
      induced in response to oxidative stress in a fashion similar to the oxidative
      response of the Mn-superoxide dismutase (MnSOD). In this study, attempts were
      made to identify the genes involved in the co-regulation of E. coli endonuclease
      and MnSOD (sodA). oh8Gua nuclease is induced by molecular oxygen and a superoxide
      radical generator (paraquat) but not by H2O2, suggesting that the regulation of
      this endonuclease is dependent on SoxRS but independent of OxyR. This enzyme was
      induced by paraquat in all of the soxRS mutant strains used (soxR-, soxS- and
      soxRc), whereas glucose-6-phosphate dehydrogenase (a member of the soxRS regulon)
      showed the expected responses; therefore, this possibility was excluded. The
      presence of metal chelators in the growth medium caused the induction of this
      enzyme, and this induction was suppressed by the addition of Fe++. Consistent
      with this finding, this enzyme was expressed under anaerobiosis in all of the
      mutant strains of fnr in particular, as well as fur, arcA, and combinations
      thereof. These findings suggest that the oxidative regulation of oh8Gua
      endonuclease is under control of fnr, fur, and arcA, where fnr plays a
      predominant role. The multiple involvement of regulatory genes as well as co
      regulation with antioxidant enzyme will enhance the efficiency of cellular growth
      and survival in the aerobic environment.

PMID- 9626575
TI  - Systemic oxidative stress and cognitive performance in the population-based EVA
      study. Etude du Vieillissement Arteriel.
AB  - The aim of this study was to examine the relationships between cognitive
      functioning and blood levels of antioxidants and lipoperoxidation products in an
      elderly population. In 1991-1992, 1389 volunteers (574 men and 815 women aged 59
      to 71 years) were recruited from the general population. Levels of selenium,
      carotenoids, and thiobarbituric-reactive substances in plasma and of vitamin E,
      glutathione peroxidase, and Cu-Zn superoxide dismutase in red blood cells were
      measured. Cognitive functioning was assessed with various psychometric tests. We
      used logistic regression to estimate the risk of poor cognitive functioning (<
      25th percentile of the score distribution) associated with low values of each
      antioxidants (< 25th percentile) including potential confounding factors. A low
      level of total carotenoids (< 1.86 mumol/l) was associated with poor cognitive
      performance in two tests assessing visual attention and logical reasoning: the
      Trail-Making Test part B [OR = 1.34 IC95% (0.99-1.81), p = .055] and the Digit
      Symbol Substitution from the WAIS-R [OR = 1.38 IC95% (1.02-1.89), p = .04]. Low
      levels of other antioxidants and high levels of thiobarbituric-reactive
      substances were not related to poor cognitive functioning. Results observed with
      plasma carotenoids are in accordance with previous data obtained mostly from
      dietary records.

PMID- 9626576
TI  - Enhancement of antioxidative ability of rat plasma by oral administration of (-)
      epicatechin.
AB  - To check whether ingestion of (-)-epicatechin (EC) affects the antioxidative
      defense in blood plasma, we studied the oxidizability of plasma from Wistar rats
      after intragastrical EC administration at 10 or 50 mg/rat. The plasma pool
      obtained from control or EC-administered rats was oxidized with copper sulfate or
      2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH). EC metabolites in plasma 1 h
      after EC administration contained glucuronide and glucuronide-sulfate conjugates
      in both the free and O-methylated form. After 6 h, the plasma concentration of
      total EC metabolites decreased and the remaining conjugates were mostly present
      as the O-methylated form. Compared to the control group, the plasma obtained from
      rats 1 and 6 h after EC administration was more resistant against copper sulfate
      induced oxidation on the basis of cholesteryl ester hydroperoxide (CE-OOH)
      accumulation. Also, the consumption of alpha-tocopherol during oxidation was
      suppressed in the plasma obtained from EC-treated rats. The content of CE-OOH and
      consumption of alpha-tocopherol in the plasma from EC-administered animals was
      much lower than those expected from the amount of nonmetabolized EC present in
      the plasma. Similar results were obtained from AAPH-induced oxidation of rat
      plasma after EC administration, except for the fact that CE-OOH accumulation was
      less suppressed in the plasma 6 h following administration. The O-methylated form
      was found to be more stable than the free form when EC-administered rat plasma
      was auto-oxidized at 37 degrees. These results suggest that EC metabolites,
      particularly conjugates in the free form, possess an effective antioxidative
      activity in blood plasma.

PMID- 9626577
TI  - Endothelial cells potentiate oxidant-mediated Kupffer cell phagocytic killing.
AB  - Phagocytosis and killing of circulating organisms by Kupffer cells (KCs) are
      discrete, important components of host defense. However, the killing mechanism(s)
      are not fully understood, and the potential role of adjacent nonparenchymal cells
      such as hepatic endothelial cells has not been defined. Rat KCs -/+ an hepatic
      endothelial cell enriched cellular fraction (HECEF) were incubated with Candida
      parapsilosis and assayed for phagocytosis and phagocytic killing by validated
      fluorochromatic vital staining. The role of reactive oxygen metabolites in KC
      phagocytic functions was examined by inhibition with superoxide dismutase and/or
      catalase. Diphenyleneiodonium and allopurinol were used to examine the potential
      roles of NADPH oxidase and xanthine oxidase, respectively, in generating these
      toxic oxidants. Coculture with HECEF increased KC phagocytic activity (from 75%
      to 88%) and candidacidal activity (from 20% to 31%). Superoxide dismutase,
      catalase, diphenyleneiodonium, or allopurinol caused inhibition of candidacidal
      activity, but did not affect phagocytosis, and did not block the potentiation of
      phagocytosis or of killing caused by coculture with HECEF. Reactive oxygen
      intermediates generated by both NADPH oxidase and xanthine oxidase-dependent
      pathways are important in KC killing of Candida parapsilosis. In vitro, KC
      phagocytosis and killing are potentiated (via a non-oxidant-mediated mechanism)
      by coculture with a preparation of hepatic non-parenchymal cells composed
      primarily of endothelial cells.

PMID- 9626578
TI  - Analysis of plasma antioxidant capacity by competition kinetics.
AB  - A competition kinetics procedure for measuring plasma antioxidant capacity is
      described. This procedure is based on the "crocin bleaching test" (Bors, W., et
      al. Biochim. Biophys. Acta 796:312-319; 1984) modified for analyzing the
      antioxidant capacity of complex mixtures (Tubaro, F., et al. J. Am. Oil Chem.
      Soc. 73:173-179; 1996). The information produced by this test is similar to that
      of the popular "total radical trapping antioxidant potential" (TRAP) analysis.
      However, the adopted kinetic approach is, in principle, more precise, taking into
      account both the concentration of antioxidants and their rate constant for the
      reaction with peroxy radical, which is overlooked in TRAP tests, as implied by
      the theory of the approach and confirmed by dynamic modeling. The kinetic
      analysis has also the advantage of accounting for the average between antioxidant
      effect (reduction of peroxy radicals) and possible prooxidant effect (oxidation
      by the radical of the antioxidant of the target supposed to be protected) if any.
      Thus, the result of this analysis provides a more precise evaluation of the
      efficiency of antioxidant defense. The intraassay variation resulted in less than
      8% and, in young healthy subjects, the plasma antioxidant capacity, expressed as
      mM equivalents of a reference antioxidant (Trolox C), gave 1.59 +/- 0.28. The
      validated procedure has been used to show that plasma antioxidant capacity is
      deeply influenced by the consumption of wine.

PMID- 9626579
TI  - Superoxide dismutase in patients with chronic hepatitis C virus infection.
AB  - It has been reported that hepatitis C virus (HCV) may cause oxidative stress in
      infected cells. Patients with chronic hepatitis C exhibit an increased production
      of tumor necrosis factor-alpha (TNF alpha), a cytokine that can produce oxidative
      stress by stimulating the generation of reactive oxygen species (ROS). Cell
      defense against ROS includes overexpression of Mn-superoxide dismutase (SOD), an
      inducible mitochondrial enzyme. To investigate cell defense against oxidative
      stress in HCV infection, we analyzed Mn-SOD mRNA in liver and in peripheral blood
      mononuclear cells (PBMC) from patients with chronic hepatitis C. Mn-SOD
      expression in PBMC was significantly increased in patients with HCV infection.
      Patients with sustained virological and biochemical response after therapy showed
      significantly lower Mn-SOD than patients with positive viremia. By contrast, Mn
      SOD expression was not enhanced in the liver of patients with chronic hepatitis
      C. The values of Mn-SOD mRNA did not correlate with TNF alpha mRNA expression,
      viral load, or liver disease activity. Our results indicate that in HCV infection
      an induction of Mn-SOD was present in PBMC but absent in the liver, suggesting
      that this organ could be less protected against oxidative damage. Oxidative
      stress could participate in the pathogenesis of HCV infection.

PMID- 9626580
TI  - Direct detection of radicals in intact soybean nodules: presence of nitric oxide
      leghemoglobin complexes.
AB  - Electron paramagnetic resonance spectroscopy has been employed to examine the
      nature of the metal ions and radicals present in intact root nodules of soybean
      plants grown in the absence of nitrate. The spectra obtained from nodules of
      different ages using this non-invasive technique show dramatic differences,
      suggesting that there are both qualitative and quantitative changes in the metal
      ion and radical species present. A major component of the spectra obtained from
      young nodules is assigned to a complex (Lb-NO) of nitric oxide (NO.) with the
      heme protein leghemoglobin (Lb). This Lb-NO species, which has not been
      previously detected in intact root nodules of plants grown in the absence of
      nitrate, is thought to be formed by reaction of nitric oxide with iron(II)
      leghemoglobin. The nitric oxide may be generated from arginine via a nitric oxide
      synthase-like activity present in the nodules of the soybean plants, in a manner
      analogous to that recently described for Lupinus albus. This Lb-NO complex is
      present at lower concentrations in older nodules, and is almost completely absent
      from senescent nodules. Exposure of young and mature nodules to oxidant stress,
      in the form of hydrogen peroxide, results in changes in the EPR spectra, with the
      loss of the signals from the Lb-NO complex and appearance of absorptions similar
      to those from untreated senescent nodules. These results suggest that there are
      characteristic changes in both the metal ion complexes and radicals present in
      intact root nodules of different ages, and support the theory that nitric oxide
      and other radicals play a significant role in determining the nitrogen fixing
      activity of root nodules; the modulatory activity of NO. may involve regulation
      of gene activity.

PMID- 9626581
TI  - Ionizing radiation and hydrogen peroxide induced oxidative DNA base damage in two
      L5178Y cell lines.
AB  - Seven oxidized DNA bases were quantified, by gas GC/MS-SIM, in chromatin from
      gamma-rays and H2O2 treated mouse lymphoma L5178Y (LY) cells, inversely cross
      sensitive to these agents. In H2O2 treated cells (2 mM, 1 h, 37 degrees C) we
      found more damage in LY-R cells than in LY-S cells. On the contrary, in gamma
      rays (400 Gy) treated cells we found more damaged DNA bases in LY-S cells. The
      yield of damaged bases in control cells was similar in both cell lines, with the
      exception of 8OHAde and FapyGua that were found at a much higher level in LY-S
      cells. The yields of damaged bases were related to cellular sensitivity to
      damaging agent; this observation points to a relationship between DNA base damage
      induction, antioxidant defense system in the intracellular milieu and cell
      sensitivity.

PMID- 9626582
TI  - Nuclear factor kappa B dependent induction of gamma glutamylcysteine synthetase
      by ionizing radiation in T98G human glioblastoma cells.
AB  - Glioblastoma is one of the most malignant of all neoplasms, and often shows
      resistance to chemotherapy and radiation therapy. Ionizing radiation activates
      transcriptional factors, such as nuclear factor kappa-B (NF-kappa B). Previously
      we found that glutathione (GSH) synthesis is induced by cytokines mediated by NF
      kappa B (Urata et al. J. Biol. Chem., 1996). Here, we present direct evidence
      that NF-kappa B activated by ionizing radiation induces the expression of gamma
      glutamylcysteine synthetase (gamma-GCS), the rate limiting enzyme of GSH
      synthesis, using T98G human glioblastoma cells. T98G cells have approximately 14
      times the level of intracellular GSH of NB9 cells, radiation-sensitive
      neuroblastoma cells. In T98G cells, 30-Gy of ionizing radiation was required for
      the activation of NF-kappa B on an electrophoretic mobility shift assay and the
      induction of gamma-GCS mRNA on Northern blots and a nuclear run-on assay.
      However, when T98G cells were treated with buthionine sulfoximine, 3-Gy of
      ionizing radiation stimulated the DNA-binding activity of NF-kappa B and the
      expression of gamma-GCS. We constructed chimeric genes containing various regions
      of gamma-GCS promoter gene and the coding region for Luciferase. T98G cells
      transiently transfected with a plasmid containing the gamma-GCS promoter
      luciferase construct showed increased luciferase activity when treated with
      ionizing radiation. The luciferase activity stimulated by ionizing radiation was
      found in the gamma-GCS promoter containing the NF-kappa B binding site, whereas
      not in that containing its mutated site. These results suggest that GSH synthesis
      is upregulated by ionizing radiation mediated by NF-kappa B and a high
      concentration of GSH in T98G cells causes downregulation of the NF-kappa B-DNA
      binding activity in response to ionizing radiation. The irresponsiveness of the
      intracellular signal transduction cascade to irradiation may be a factor in the
      resistance of T98G cells to radiation therapy.

PMID- 9626583
TI  - Dietary restriction augments protection against induction of the mitochondrial
      permeability transition.
AB  - Exposure to oxidants or phosphate, especially in the presence of calcium, has
      been long known to lead to mitochondrial structural alteration and damage. In the
      past 15 years, it has become increasingly appreciated that this damage is often
      the result of a cyclosporin A-sensitive event, the "permeability transition"
      (PT). Using liver mitochondria isolated from male Fischer 344 rats of 6-24 months
      of age, we now present evidence that long-term, life-prolonging, dietary
      restriction regimens greatly delay induction of a PT following challenge. Dietary
      restriction slowed induction by 25 microM calcium, or by calcium in conjunction
      with the strong oxidant t-butyl hydroperoxide, by approximately 50%. The
      increased resistance to PT induction was maintained through 24 months of age.
      Dietary restriction also protected against t-butyl hydroperoxide in the presence
      of high calcium challenges (250 microM), although the extent of this protection
      was age-dependent. Induction by 2.5 mM phosphate alone was blocked in most 6
      month-old dietary restricted animals and was slowed by 50-100% in animals 12-24
      months of age. Susceptibility to 25 microM calcium in conjunction with phosphate
      varied in an age-dependent manner, ranging from 4-12 times slower in the dietary
      restricted animals than in their ad lib fed counterparts. Together, these data
      provide evidence that the factors regulating PT induction are affected by long
      term physiological and environmental conditions such as age and diet. The
      observed effects represent one of the largest recognized dietary restriction
      mediated increases in a parameter related to antioxidant defenses. These data
      also suggest that the endogenous defense systems that protect mitochondria from
      calcium in conjunction with inorganic phosphate differ from those that protect
      against calcium in conjunction with an oxidant.

PMID- 9626584
TI  - Fluorescent lipid oxidation products and heme spectra index antioxidant efficacy
      in kidney tissue of hamsters.
AB  - Studies ranging from epidemiological to molecular suggest that dietary
      antioxidants protect against chronic diseases. The hypothesis was investigated
      that hamster kidney homogenate are better protected against induced oxidative
      damage after animals were fed a purified vitamin E deficient diet supplemented
      with 30 international units (IU) vitamin E/kg (30 IU diet) than fed the minimum
      required 3 IU vitamin E/kg (3 IU diet). The addition of 200 mg (+)-catechin to
      the 3 IU diet may offer protection. The effects of dietary (+)-catechin and alpha
      tocopherol on tissue oxidizability were investigated by measuring (i) fluorescent
      products in lipid extracts, (ii) heme protein oxidation and (iii) heme
      destruction. A rapid initial increase of oxidation markers was measured over the
      4 h incubation period for iron + ascorbate induced oxidation and a constant
      increase for lipoxygenase catalyzed products. Analysis of covariance over time
      and comparison at specific incubation times showed that iron + ascorbate induced
      homogenates from hamsters fed the 30 IU diet generated less fluorescent products
      and oxidized heme proteins than homogenates from the 3 IU or the 3 IU plus (+)
      catechin fed animals. Incubation with lipoxygenase produced more lipid
      fluorescent products and heme protein oxidation in the 3 IU than in the 30 IU
      vitamin E group. In conclusion, supplementary dietary vitamin E but not
      supplementary (+)-catechin in a diet containing the minimum requirement of
      vitamin E for the species enhances oxidative resistance of kidney tissue.

PMID- 9626586
TI  - LDL-associated phospholipase A does not protect LDL against lipid peroxidation in
      vitro.
AB  - The irreversible proteinase inhibitor Pefabloc (4-[2-aminoethyl] benzenesulfonyl
      fluoride) inactivates LDL-catalyzed hydrolysis of the short-chain fluorescent
      phospholipid C6-NBD-PC (1-acyl-2-(N-4-nitrobenzo-2-oxa-1,3-diazole)-aminocaproyl
      phosphatidylcholine). The dose-dependence of this inactivation is similar to that
      obtained previously for the inhibitory effect of Pefabloc on the hydrolysis of
      platelet activating factor (PAF) by the LDL-associated PAF acetylhydrolase (PAF
      AH), in agreement with the notion that the hydrolysis of C6-NBD-PC and PAF is
      catalyzed by the same enzyme (LDL-associated phospholipase A; LDL-PLA). This
      conclusion is also supported by the finding that hydrolysis of C6-NBD-PC by LDL
      becomes inactivated by LDL oxidation only at late stages of the oxidation,
      similar to the effect of oxidation on the hydrolysis of PAF by the LDL-associated
      PAF-AH. Under conditions of complete inactivation of this enzyme towards C6-NBD
      PC, the kinetics of lipid peroxidation, induced either by copper ions or by the
      free radical generator AAPH at varying doses of the prooxidant, was similar to
      that observed when the PLA was active (i.e., in the absence of Pefabloc). Hence,
      LDL-associated PLA (PAF-AH) does not protect LDL lipids from peroxidation.
      Similar results were obtained with fractionated LDL in albumin-containing buffer
      and for non-fractionated serum, in which copper-induced peroxidation was also not
      influenced by inactivation of the enzyme responsible for hydrolysis of C6-NBD-PC.
      Phospholipolysis of short chain phospholipids by LDL-PLA may still play a
      protective role against the toxic effects of oxidized phospholipids by reducing
      their internalization into cells (Schmitt et al. 1995).

PMID- 9626585
TI  - Involvement of free radicals and histamine in the potentiating action of
      cigarette smoke exposure on ethanol-induced gastric mucosal damage in rats.
AB  - Cigarette smoking has been associated with peptic ulcer diseases. We studied the
      effects of cigarette smoke exposure on ethanol-induced gastric mucosal damage and
      its relationship with vascular integrity and the possible role of free radicals
      and histamine. Male Sprague-Dawley rats were exposed to cigarette smoke followed
      by ethanol administration (70% v/v). Smoke exposure alone dose-dependently
      reduced basal blood flow and increased xanthine oxidase (XO) activity but
      superoxide dismutase (SOD) activity remained unaffected in gastric mucosa.
      Cigarette smoking followed by ethanol administration significantly potentiated
      mucosal lesion formation along with augmentation of the mucosal blood flow,
      vascular permeability and myeloperoxidase (MPO) activity. The potentiating effect
      of smoking on ethanol-induced gastric mucosal lesion and MPO activity was
      abolished by pretreatment with allopurinol, terfenadine or ranitidine.
      Terfenadine and ranitidine also reduced the increased mucosal blood flow and
      vascular permeability induced by smoking and ethanol combined. These findings
      suggested that cigarette smoke adversely affected the defense mechanisms of the
      gastric mucosa by reducing the mucosal blood flow which in turn led to ischemia
      and increased XO activity. Activation of XO together with histamine H1 and H2
      receptors stimulation could lead to neutrophil aggregation and vascular damage.
      However, the potentiating action of cigarette smoke on ethanol ulceration is
      unlikely through reduction of SOD activity in gastric mucosa.

PMID- 9626587
TI  - Direct, real-time sensing of free radical production by activated human
      glioblastoma cells.
AB  - Primary brain injury initiates a cascade of events which result in secondary
      brain damage. Although, at present, the biochemical and molecular mechanisms of
      nerve cell death are not well understood, sufficient evidence now exists to
      implicate free radicals in this brain injury response. In the light of the
      current understanding on the role of free radicals in cell mortality, we report
      on the use of two specific sensors, which we use to measure the direct,
      simultaneous and real time electrochemical detection of both superoxide (O2.-)
      and nitric oxide (NO), produced by activated glioblastoma cells. The development
      and application of these novel methods has enabled us to show that both the
      cytokine-mediated induction of the enzymes responsible for the generation of
      these radical species, and the metabolic requirements of the cell can modulate
      cell messenger release. Importantly, the data collected provides dynamic
      information on the time course of free radical production, as well as their
      interactions and their involvement in the process of cell death. In particular,
      one of the major advances afforded by this technology is the demonstration that
      suppression of one of either of the two cellular generated radical species (NO
      and O2.-) leads directly to a corresponding increase in the species that was not
      being deliberately inhibited or scavenged. This finding may indicate a mechanism
      involving inter-enzyme regulation of free radical production in glial cells (a
      phenomenon which may, in future, also be shown to operate in other relevant cell
      models).

PMID- 9626588
TI  - Detection of DNA damage in stressed trout nucleated erythrocytes using the comet
      assay: protection by nitroxide radicals.
AB  - Because previous literature reports have demonstrated that nucleated trout
      erythrocytes in conditions of oxidative stress are subjected to both membrane
      damage and a decrease in the enzymatic defense systems (glutathione peroxidase),
      which in turn lead to hemolysis, the present study was undertaken to determine
      whether DNA may be affected too, prior to the hemolytic event. Impairment of DNA
      in stressed trout erythrocytes was assessed using the comet assay--a rapid and
      sensitive, single-cell gel electrophoresis technique used to detect primary DNA
      damage in individual cells. In addition, indolinic and quinolinic nitroxide
      radicals were included in the study to determine their efficacy as antioxidants
      against free-radical-induced DNA damage. The parameters, tail length, tail
      intensity, and tail moment, used as an index of DNA damage, have shown that trout
      erythrocytes exposed to oxidative stress experience DNA damage prior to hemolysis
      and that the nitroxides significantly prevent this damage. This result provides
      further information about the potential use of these compounds as antioxidants in
      biological systems.

PMID- 9626589
TI  - Cold-induced release of reactive oxygen species as a decisive mediator of
      hypothermia injury to cultured liver cells.
AB  - The mechanisms of hypothermia-induced cell injury are still unclear. The present
      study provides experimental evidence for the involvement of reactive oxygen
      species in hypothermia injury: cultured rat hepatocytes incubated in cold (4
      degrees C) Krebs-Henseleit buffer or cell culture medium were injured under
      normoxic conditions and even more so under hyperoxic conditions, whereas the
      hepatocytes were protected under hypoxic conditions. During warm (37 degrees C)
      incubation in cell culture medium, on the other hand, cell injury was minimal
      under normoxic conditions, only slightly increased under hyperoxic conditions,
      but substantially increased under hypoxic conditions. The injury occurring during
      cold normoxic incubation was also largely decreased by the addition of the spin
      trap 5,5-dimethyl-1-pyrroline N-oxide, the hydroxyl radical scavenger dimethyl
      sulfoxide, the flavonoid silibinin, or the transition metal chelator 2,2'
      dipyridyl to the medium, or by preincubating the cells with the iron chelator
      deferoxamine or the lipophilic antioxidant alpha-tocopherol before the
      hypothermic incubation. In addition, marked lipid peroxidation was observed
      during cold incubations without inhibitors, but not during warm incubations.
      Similar results were obtained with cultured rat liver endothelial cells. These
      results suggest that in hepatocytes and in liver endothelial cells, cold-induced
      release of reactive oxygen species, most likely of hydroxyl radicals, is the main
      injurious factor under hypothermic conditions.

PMID- 9626590
TI  - Production of reactive oxygen species by microsomes enriched in specific human
      cytochrome P450 enzymes.
AB  - Few studies have evaluated the production of reactive oxygen intermediates by
      human microsomes, especially the influence of the specific form of cytochrome
      P450. Experiments were carried out to evaluate the ability of CYP1A1, 1A2, 2B6,
      and 3A4 to consume NADPH, reduce iron, and catalyze production of reactive oxygen
      species. Microsomes enriched in each of these CYPs were obtained from commercial
      +/- lymphoblast cells that had been transfected with cDNA encoding the specific
      human CYP. On a per nanomole cytochrome P450 basis, CYP3A4 was the most active
      P450 evaluated in catalyzing NADPH oxidation, production of superoxide anion
      radical, NADPH-dependent chemiluminescence, oxidation of dichlorofluorescein
      diacetate, and reduction of either ferric-EDTA or ferric-citrate. CYP1A1 was the
      next most reactive CYP, whereas CYP1A2 and 2B6 displayed a comparable, lower
      activity. Nitric oxide, which reacts with and inactivates hemoproteins, inhibited
      superoxide production by all the CYPs to a similar extent. Because CYP3A4 is
      present in high amounts in human liver microsomes and is active in catalyzing the
      formation of reactive oxygen species, this CYP may make an important contribution
      in the overall ability of human liver microsomes to generate active oxygen
      species.

PMID- 9626591
TI  - Slowing of peroxynitrite decomposition in the presence of mannitol and ethanol.
AB  - The kinetics of peroxynitrite decomposition in the presence of the hydroxyl
      radical scavengers mannitol and ethanol were studied by stopped-flow
      spectrophotometry. Mannitol and ethanol decreased the rate of peroxynitrite
      decomposition in a concentration-dependent manner, following a hyperbolic
      function. The decreases in peroxynitrite decay rates were observed all throughout
      the pH range 5.8 to 8.0. In the presence of 100 mM mannitol or ethanol, the first
      order rate constant for peroxynitrite decomposition changed from 1.25 +/- 0.01 s
      1 at 25 degrees C, to values of 0.83 +/- 0.01 s-1 and 0.95 +/- 0.01 s-1,
      respectively. One explanation for this decrease in the rate of peroxynitrite
      decay with mannitol and ethanol could be a stabilizing effect of the substrate by
      hydrogen bonding with peroxynitrite, analogous to what has been recently proposed
      for hydrogen peroxide (Alvarez, B., Denicola, A. and Radi, R. Chem. Res. Toxicol.
      8:859-869; 1995). In this sense, kinetic data fitted a mechanism implying fast
      equilibria between peroxynitrite anion and peroxynitrous acid with the substrates
      to form the corresponding complexes. The equilibrium constants of complex
      dissociation were estimated to be (6.7 +/- 0.9) x 10(-3) M and (9.6 +/- 1.5) x
      10(-3) M for mannitol and ethanol, respectively. When bonded to mannitol or
      ethanol, peroxynitrous acid could ionize, too, or decompose at a slower rate than
      in the absence of substrate, in part to a reactive intermediate which performs
      oxidations. While mannitol and ethanol inhibit oxidation and nitration processes
      that occur through the reaction of secondary reactive intermediates of
      peroxynitrite with target molecules, up to 0.5 M mannitol or ethanol failed to
      inhibit cysteine oxidation by peroxynitrite at pH 7.4 and 25 degrees C. Thus, the
      formation of stabilizing complexes would not divert the reaction yield of direct,
      second order reactions such as thiol oxidation, but highlights the importance of
      hydrogen bonding and solvent effects on peroxynitrite stability.

PMID- 9626592
TI  - The structure of heme proteins Compounds I and II: some misconceptions.
AB  - Many reactions catalyzed by heme proteins involve an oxidation of the heme to one
      or two equivalents above the ferric state. Such intermediates are often referred
      to as Compound II and Compound I, respectively. Several different notations are
      used in the literature to describe the chemical structures of these compounds,
      which has led to errors and misinterpretations. The main problems are: 1. For
      many biochemists the notations X - FeIV = O and X - Fe + = O are equivalent and
      are used interchangeably, whereas other biochemists interpret these notations to
      have quite different meanings. 2. It is inaccurate and misleading to illustrate
      the increased oxidation state of Compound I by just adding two positive charges
      to the structure. 3. The bond between the oxygen and iron is not a conventional
      double bond and illustrating it as such leads to misconceptions concerning its
      properties. 4. In several instances, including horseradish peroxidase Compound I,
      there is reason to doubt that the radical moiety of the porphyrin ring (or of the
      protein in other peroxidases) carries a positive charge. The purpose of this
      article is to promote the use of uniform, as well as chemically correct, formulae
      and equations in describing the structures and reactivities of Compounds I and
      II. To accomplish this, a new notation is proposed for the iron-oxygen bond in
      these compounds.

PMID- 9626593
TI  - Effect of stobadine on carbon tetrachloride-induced erythrocyte membrane changes
      in rats.
AB  - Our previous study showed that stobadine is effective against
      ischemia/reperfusion-induced gastric mucosal injury. The present study examined
      the ability of stobadine to protect erythrocyte membrane against free radical
      injury after long-term carbon tetrachloride (CCl4) application. The erythrocyte
      membrane changes were established using colloid-osmotic hemolysis. The
      significant increase of colloid-osmotic hemolysis was found in animals treated
      with CCl4. CCl4 also increased formation of thiobarbituric acid-reactive
      substances (TBARs) and decreased thiol group content. Stobadine in both doses
      (10.0 and 20.0 mg.kg-1) protected erythrocyte membrane against CCl4-induced
      injury. The membrane lipid bilayer is the most affected part of the erythrocyte
      membrane. In presence of stobadine, CCl4-induced lipid peroxidation was partially
      or totally prevented whereas the level of total membrane thiols was increased.
      Based on these results, it can be concluded that protective effect of stobadine
      on CCl4-induced erythrocyte membrane changes should be related to its antioxidant
      properties.

PMID- 9626594
TI  - Apomorphine does not influence olfactory thresholds in Parkinson's disease.
AB  - In order to verify the presumed dopaminergic basis of olfactory dysfunction in
      Parkinson's disease (PD), we studied olfactory functions in 12 PD patients (mean
      age 60.1 yrs, mean duration of PD 9.0 yrs, mean Hoehn and Yahr score 2.8) before
      and after apomorphine (APO) administration. Amylacetate (banana smell) in 12
      sequential dilutions (in 50% steps) was used for the examination of olfactory
      thresholds. The testing showed no significant differences in any olfactory
      parameters before and after APO. Furthermore, when analysing the subgroup of 7
      hyposmic PD patients, we also found no significant differences before and after
      APO. We therefore believe that olfactory dysfunction in PD is not dependent on
      dopamine deficiency.

PMID- 9626595
TI  - Pallidotomy improves quality of life in selected parkinsonian patients: an
      Italian report.
AB  - Pallidotomy has recently been reconfirmed as effective for otherwise intractable
      symptoms of Parkinson's disease. Nonetheless almost every aspect of its
      performance requires choices which are not fully established and may vary between
      centers. These include: 1) patient selection; 2) choice of imaging modality, 3)
      choice of anatomic landmarks for targeting the lesion, 4) choice of method for
      physiologic confirmation of location, 5) choice of lesion size and shape. We
      present two cases of pallidotomy procedures in Parkinsonian patients that in our
      knowledge are the first reported in Italy. Our experience and a careful review of
      the literature led to the following choices: 1) selection of Parkinsonian
      patients with dominant L-Dopa induced dyskinesia, akinetic and rigidity symptoms,
      2) use of CT due to the distortion effects of MRI, 3) use of standard (Laitinen)
      coordinates combined with an image fusion method using MRI, 4) use of stimulation
      to gauge distance to internal capsule and optic tract, 5) production of vertical
      lesion covering internal segment of pallidum. At a 1-year follow-up the results
      include a 45% drop in UPDRS (Unified Parkinson's Disease Rating Scale) motor
      score and almost complete resolution of contralateral dopa induced dyskinesias in
      both patients.

PMID- 9626596
TI  - Patient education and migraine: a pilot study.
AB  - Our study examines the effectiveness of an educational approach to migraine
      patients. A course in migraine education was set up for 30 patients suffering
      from this disease; meetings were structured taking into consideration specific
      educational aims, with parameters evaluated before the course, at the end of the
      course and at a 3-month follow-up. The results, particularly the increase in the
      migraineurs' knowledge of their disease and the decrease in the use of
      symptomatic drugs, suggest the effectiveness of the course. Furthermore, our
      study suggests that there is a need to build educational processes into
      therapeutic protocols, as they enable patients to manage their chronic diseases
      more correctly.

PMID- 9626597
TI  - The "skin roll" test: a diagnostic test for cervicogenic headache?
AB  - Skin roll tests were performed on 15 patients with cervicogenic headache, 15 with
      tension headache ("tension-type headache"; 6 with the acute ("episodic") and 9
      with the chronic form), and 43 migraine without aura patients (15 without and 28
      with sideshift). Three positions (trapezius, mandibular, supraorbital) were used.
      The results were compared with those obtained in a control series (no. = 95).
      Fourteen cervicogenic (93.3%), 8 tension headache (53.3%), and 8 migraine (18.6%)
      patients reported tenderness in the trapezius position during the procedure.
      Tenderness asymmetry of > or = 10 mm on the visual analogue scale (with the
      highest value on the symptomatic side; trapezius position) was found in 10 (67%)
      cervicogenic headache patients, vs 3 (20%) tension headache patients and no
      migraine patients. A clear tenderness asymmetry in this area may suggest a
      cervicogenic headache rather than a migraine without aura diagnosis. Thickness
      values were less helpful in distinguishing cervicogenic headache from other
      headaches. In the cervicogenic headache group, both tenderness and skinfold
      thickness showed significantly higher values on the symptomatic than on the non
      symptomatic side in the trapezius position, but not in the other positions. The
      differences between cervicogenic headache on the one hand and tension
      headache/migraine on the other were generally rather small, indeed, there was a
      considerable overlap between the groups. In single cases, therefore, the skin
      roll test will contribute little to the differential diagnosis of cervicogenic
      headache.

PMID- 9626598
TI  - Trigeminal evoked potentials in man: a new olfactory stimulation device.
AB  - The recording of olfactory evoked potentials in healthy humans, using a
      continuous flow olfactory stimulator, is described. A stimulator pushed inert gas
      (N2) in a continuous flow through the nose at a rate of 4 l/min. At fixed 30
      second intervals, (32 times) the flow was replaced by an equal amount of CO2, a
      trigeminal stimulant. Each pulse lasted 200 ms. An electronic timing circuit
      triggered both the stimulator and the recorder. Signal acquisition was performed
      using an Evoked Potential Recorder (Nicolet Compact Four by Nicolet Biomedical
      Instruments), triggered by the stimulator. Using this stimulator device reliable
      olfactory evoked potentials can be recorded in a clinical setting. Since this is
      a non invasive technique which can be used to test olfactory function whether or
      not the patient cooperates, it is expected to become widely used, particularly in
      non collaborating patients and in those suspected of malingering.

PMID- 9626599
TI  - Whole blood cytokine assays--a new generation of diagnostic tests for
      tuberculosis?

PMID- 9626600
TI  - Sensitivity and specificity of a gamma interferon blood test for tuberculosis
      infection.
AB  - SETTING: Victoria, Australia. OBJECTIVE: To determine the sensitivity and
      specificity of a gamma interferon (IFN-gamma) blood test for tuberculosis
      infection. DESIGN: Heparinised blood samples from 952 volunteers were analysed
      using the QuantiFERON-TB blood test. The levels of IFN-gamma in whole blood
      aliquots stimulated in vitro with human, avian or bovine purified protein
      derivative (PPD), or phytohaemagglutinin (PHA), were compared to tuberculin
      reactivity and clinical presentation. RESULTS: IFN-gamma (IU/ml) responses were
      expressed as % PPD/PHA response ratios. The proportion of responders detected by
      both the IFN-gamma assay and tuberculin skin test (TST) was not significantly
      different when the % human PPD response ratio was 15%. Using this threshold, the
      specificity of the IFN-gamma assay was 98% (407/417 individuals with no known
      exposure to tuberculosis were negative) and sensitivity was 90% (163/182
      untreated TST reactors were positive). The test detected positive responses in
      83% (10/12) of individuals with proven active disease, 59% (24/41) of those
      previously treated, 80% (134/168) of those with untreated inactive disease, and
      43% (55/128) of those exposed but TST-negative. CONCLUSION: The measurement of
      IFN-gamma released from PPD-stimulated blood lymphocytes is a specific, sensitive
      and rapid method of detecting Mycobacterium tuberculosis infection. The IFN-gamma
      assay may be a useful and practical tool for the early diagnosis of tuberculosis
      infection, especially in immunocompetent individuals.

PMID- 9626601
TI  - Comparison of three different primer pairs for the detection of Mycobacterium
      tuberculosis by polymerase chain reaction in paraffin-embedded tissues.
AB  - SETTING: More than five different primer pairs have been used for the detection
      of Mycobacterium tuberculosis deoxyribonucleic acid (DNA) with the polymerase
      chain reaction (PCR). OBJECTIVE: The sensitivity and specificity of PCR were
      evaluated using three different primer pairs in the detection of M. tuberculosis
      in paraffin-embedded tissues. DESIGN: Thirty-eight tissue specimens from 23
      patients were studied. Eighteen samples were obtained from 10 tuberculosis
      patients, and 20 samples obtained from 13 patients with other diseases were used
      as negative controls. DNA extracted from paraffin-embedded tissues was used
      directly for PCR amplification using primers IS1 and IS2 to amplify a 123 base
      pair (bp) region of IS6110, sjMT3 and sjMTr2 to amplify a 281 bp region of
      protein antigen b, and INS1 and INS2 to amplify a 245 bp region of IS986. Each
      amplification was performed double-blinded and repeated three times including
      positive and negative control samples. RESULTS: IS1 and IS2 gave a positive
      result in each of the double samples obtained from eight tuberculosis patients
      and in the single samples obtained in the two others, sjMT3 and sjMTr2 detected
      13 of the 18 tuberculosis samples, and INS1 and INS2 detected only three of the
      18. CONCLUSION: These results highlight the importance of selecting appropriate
      primers to obtain high sensitivity in detecting M. tuberculosis in paraffin
      embedded tissues by PCR.

PMID- 9626602
TI  - Role of antigen specific circulating immune complexes in diagnosis of
      tuberculosis.
AB  - SETTING: Tuberculosis is a public health problem worldwide. Early accurate
      diagnosis in patients with active disease is essential to reduce morbidity and
      mortality. Conventional methods for detection of Mycobacterium tuberculosis have
      given disappointing results. OBJECTIVE: To evaluate the utility of detection of
      M. tuberculosis antigen in circulating immune complexes (CIC) for the diagnosis
      of tuberculosis. METHOD: Eighty-four clinically diagnosed cases of mainly extra
      pulmonary tuberculosis, 85 patients with diseases other than tuberculosis and 30
      healthy controls, were evaluated for the presence of antigen of M. tuberculosis
      in CIC in serum using sandwich enzyme linked immunosorbent assay (ELISA).
      RESULTS: In total, 22 out of 84 cases were positive for culture on Lowenstein
      Jensen medium; 76.5% (n = 65) of the clinically diagnosed patients (including 20
      culture-positive cases) were found to be positive by ELISA. The difference in
      mean absorbance values of ELISA in cases of tuberculosis was significantly higher
      than in controls. The sensitivity of ELISA was 90.9% and the specificity was
      93.04%. CONCLUSION: Detection of M. tuberculosis antigen in CIC by ELISA has
      potential as a useful diagnostic tool for the rapid diagnosis of tuberculosis,
      especially extra-pulmonary forms where results of conventional methods of
      diagnosis are disappointing.

PMID- 9626603
TI  - Clarithromycin with minocycline and clofazimine for Mycobacterium avium
      intracellulare complex lung disease in patients without the acquired immune
      deficiency syndrome. GETIM. Groupe d'Etude et de Traitement des Infections a
      Mycobacteries.
AB  - SETTING: An open clinical trial for the treatment of Mycobacterium avium
      intracellulare complex (MAIC) lung disease in human immunodeficiency virus (HIV)
      seronegative patients. OBJECTIVE: To assess the efficacy and tolerance of
      clarithromycin (0.75-2 g/day) combined with minocycline (200 mg/day) and
      clofazimine (100 mg/day) for 15 months. DESIGN: The study was carried out from
      August 1992 to June 1994 by pulmonologists of various French medical centres. The
      patients to be enrolled were of either sex, over 18 years of age, HIV
      seronegative and suffering from MAIC lung disease, with a confirmed
      bacteriological and radiological diagnosis. Examinations were to be performed
      after 1, 2, 3, 6, 9, 12 and 15 months of treatment. RESULTS: Thirty patients were
      included, 16 males and 14 females. Eight did not complete the study due to
      deviations from protocol or adverse effects. The remainder completed the study
      with a post-treatment follow-up of 27 +/- 7 months. Among the 22 evaluable
      patients, 18 had a history of lung disease. Tolerance to the drugs was generally
      good, apart from three cases of hepatic disturbances and three cases of
      ototoxicity, which required a decrease in clarithromycin dosage after a short
      interruption of treatment. There were 14 treatment successes, seven treatment
      failures, defined by absence of bacteriologic conversion, and in one patient the
      disease evolution remains uncertain. CONCLUSION: The combination of
      clarithromycin with minocycline and clofazimine proved effective with
      persistently negative cultures in 64% of the patients, and an overall good drug
      tolerance.

PMID- 9626604
TI  - Towards a standardized approach to DNA fingerprinting of Mycobacterium bovis.
      International Union Against Tuberculosis and Lung Disease, Tuberculosis in
      Animals Subsection.
AB  - The Tuberculosis in Animals Subsection of the International Union Against
      Tuberculosis and Lung Disease (IUATLD) recently identified a need to standardize
      the deoxyribonucleic acid (DNA) strain typing of Mycobacterium bovis. The
      standard method for strain typing of M. tuberculosis isolates cannot be directly
      extrapolated to M. bovis due to the low copy number of IS6110 identified in the
      majority of M. bovis strains, particularly from cattle. To improve the resolution
      of M. bovis strains, alternative methods and additional DNA probes have been
      investigated. In combination with studies of published literature, laboratories
      performing M. bovis DNA fingerprinting were surveyed. Results of these surveys
      allowed us to reach consensus and to make recommendations for DNA typing of M.
      bovis isolates, which hopefully will lead towards a standardized approach to the
      DNA fingerprinting of this organism. This approach, in conjunction with
      conventional epidemiological traceback approaches, should facilitate more
      accurate and effective investigations into the epidemiology, maintenance and
      transmission of M. bovis within and between man and domesticated, feral and wild
      animals, both at a local and a global level.

PMID- 9626605
TI  - Determinants of tuberculosis in an immigrant population in Rome: a case-control
      study.
AB  - SETTING: An out-patient clinic for immigrants in Rome, Italy. OBJECTIVE: To
      determine risk factors for tuberculosis among immigrants in Italy. DESIGN: Case
      control study. Cases comprised 44 individuals aged 15-55 years who had a first
      diagnosis of tuberculosis between 1989 and 1994 at the clinic. Controls comprised
      264 individuals randomly recruited among immigrants who attended the clinic for
      other reasons within seven days before or after the case was diagnosed. Subject
      information included country of origin, date of first arrival in Italy, level of
      education, knowledge of the Italian language, and legal resident status. RESULTS:
      An increase of tuberculosis risk was observed with increasing tuberculosis
      incidence in the country of origin. Multivariate analysis showed an increased
      risk for those coming from Central and South America (odds ratio [OR] 5.5; 95%
      confidence interval [CI] 1.6-18.7). The adjusted odds ratio by time since entry
      in Italy increased during the second year of residence (OR 2.8; 95% CI 1.1-7.0),
      but decreased after that period. A trend toward increasing risk with decreasing
      educational level was observed. CONCLUSIONS: These results demonstrate the need
      for a public health policy in Italy for tuberculosis control among immigrants
      which includes screening, prophylaxis and treatment.

PMID- 9626606
TI  - Multidrug-resistant tuberculosis in the Florence province from 1992 to 1995.
AB  - SETTING: Epidemiological data on the frequency of drug-resistant tuberculosis is
      not available in Italy. OBJECTIVES: Evaluation of the rate of multidrug-resistant
      tuberculosis in the Province of Florence, Italy. DESIGN: Retrospective analysis
      of all sensitivity tests performed with the Bactec method on initial
      mycobacterial isolates, from 1 January 1992 to 31 December 1995, in the Province
      of Florence. RESULTS: The following rates of resistance were found in the 433
      samples tested: isoniazid + rifampicin 2.5%, at least one drug 13.8%, isoniazid
      10.6%, rifampicin 3.6%, streptomycin 3.6%, pyrazinamide 1.7% and ethambutol 0.6%.
      Resistance was higher in foreign-born individuals from high prevalence countries
      than in the Italian-born population, whereas resistance to streptomycin was more
      frequent in the latter. The yearly rates of resistance showed no significant
      variation in the period examined. Clinical data were available in 231 patients:
      the rate of resistance to at least one drug and to isoniazid + rifampicin were
      10.8% and 0%, respectively, in never treated patients, and 28.5% and 7.1%,
      respectively, in previously treated patients. CONCLUSION: These data show higher
      multidrug resistance rates than those found in other European countries such as
      England and Wales, France and Switzerland. This result suggests the need to
      establish official guidelines for the correct treatment of tuberculosis in Italy,
      in order to prevent the onset of drug resistance, and to establish a national
      surveillance system for mycobacterial resistance.

PMID- 9626607
TI  - Drug-resistant tuberculosis in the Dominican Republic: results of a nationwide
      survey.
AB  - SETTING: The Dominican Republic. OBJECTIVE: To assess the extent of drug
      resistant tuberculosis (TB) following the guidelines of the World Health
      Organization (WHO)/International Union Against Tuberculosis and Lung Disease
      (IUATLD) new global surveillance project on drug resistance in TB. METHODS: Using
      a multi-step proportional weighted approach, a sample of 688 sequential cases of
      smear positive pulmonary TB diagnosed between April 1994 and April 1995 was
      studied in six of the country's eight health regions. Pre-treatment sputum
      samples were cultured on Loewenstein-Jensen medium and drug susceptibility tests
      were performed using the economic variant of the proportion method. RESULTS: Of
      420 cases with drug susceptibility results, resistance to one or more drugs was
      observed in 43.8%; resistance was found in 52.1% of 117 TB cases with a history
      of previous antituberculosis treatment and in 40.6% of 303 new TB cases. In five
      of the six health regions surveyed, > or = 41% of strains were resistant to one
      or more drugs. Multidrug resistance (MDR) to isoniazid and rifampicin with or
      without resistance to other drugs was found in 43 (10.2%) of 420 cases, including
      6.6% of new TB cases. In five of the six health regions > or = 8% of strains were
      classified as MDR. Independent predictors of MDR-TB included being in the age
      group 25 to 44 years (odds ratio [OR] = 4.2, 95% confidence interval [Cl] 1.5,
      11.6; P = 0.005), being aged 45 years and over (OR = 4.5, 95% CI 1.4, 14.4; P =
      0.009), and having a prior history of TB (OR = 3.7, 95% CI 1.9, 7.4; P = 0.0001).
      CONCLUSION: The proportion of Mycobacterium tuberculosis strains resistant to one
      or more anti-TB drugs in the Dominican Republic is among the highest observed
      world-wide. The severity of the problem urgently requires the full implementation
      of TB control strategies endorsed by the WHO and the IUATID, which include
      political commitment to a National TB Program, case detection utilizing sputum
      smear microscopy, directly observed treatment, regular drug supply, and
      standardised recording and reporting systems. Also, the sale of TB drugs in the
      private market should be controlled.

PMID- 9626608
TI  - Antituberculosis drug resistance surveillance in Kenya, 1995.
AB  - SETTING: Twenty-two of the 42 administrative districts in Kenya. OBJECTIVE: To
      determine the prevalence of drug resistance in newly diagnosed patients with
      pulmonary tuberculosis, to determine possible risk factors associated with
      resistance, and to establish standard routine surveillance of drug resistance.
      DESIGN: Cross-sectional study. METHODS: Sputum samples from newly diagnosed
      patients with smear-positive pulmonary tuberculosis were analysed using standard
      procedures. RESULTS: Of 638 patients, 85% were culture positive for Mycobacterium
      tuberculosis. Of 491 patients tested for susceptibility to isoniazid,
      streptomycin, rifampicin and ethambutol, 90.8% had fully sensitive strains and
      9.2% had a strain resistant to one or more drugs. Of 445 patients with no history
      of previous chemotherapy, 6.3% had a resistant strain. Of 46 patients with a
      history of previous chemotherapy, 37% had a resistant strain. No resistance to
      either rifampicin or ethambutol was detected. There was a strong association
      between previous chemotherapy and resistance. Resistance was not associated with
      age or sex. High concordance between Kenya's results and those of the
      Mycobacterium Reference Unit in the UK on both drug-sensitive and drug-resistant
      strains indicates that clinically significant and comparable data can be obtained
      from laboratories employing unsophisticated and inexpensive standard procedures.
      CONCLUSION: Rates of initial drug resistance are still low in Kenya. The increase
      in acquired resistance to isoniazid requires monitoring.

PMID- 9626609
TI  - A clinical trial of a financial incentive to go to the tuberculosis clinic for
      isoniazid after release from jail.
AB  - SETTING: Screening for active tuberculosis (TB) and providing isoniazid (INH)
      preventive therapy in jails are important control measures. In San Francisco,
      however, historical data showed that 62% of inmates were released before
      completing preventive therapy, and of those only 3% attended the TB Clinic for
      follow-up. OBJECTIVE AND DESIGN: A randomized clinical trial to compare a $5 cash
      incentive plus standardized TB education with standardized TB education alone in
      encouraging released inmates to make a first visit to the clinic. RESULTS: Of 79
      persons enrolled in the trial, 77.2% were released before INH completion. Rates
      of first visit were not significantly different for those receiving +5 plus
      standardized education (25.8%) versus standardized education alone (23.3%), but
      were higher than rates seen in historical data for inmates not receiving
      standardized education. Age was an important predictor of completion of a first
      visit (odds ratio 1.09, 95% confidence interval 1.02-1.16, P = 0.017). Other
      variables predicting adherence included intent to adhere, more previous time in
      jail, stable housing, and being partnered versus alone, although these were not
      statistically significant. CONCLUSION: Standardized education may be important in
      improving follow-up after release. Further work on the role of a financial
      incentive in this population is needed.

PMID- 9626610
TI  - Tuberculous pleurisy with or without radiographic evidence of pulmonary disease.
      Is there any difference?
AB  - SETTING: A community teaching hospital in Alicante, Spain. OBJECTIVE: To assess
      the characteristics of tuberculous pleurisy (TP) in our hospital, and to evaluate
      the differences between primary and reactivation forms. DESIGN: Between January
      1984 and December 1993, all human immunodeficiency virus (HIV)-negative patients
      with TP were included in the study. From September 1987 onward, patients were
      prospectively studied. Charts, radiography, pleural fluid findings and diagnostic
      methods were evaluated. Two groups were distinguished according to chest
      radiographs: those patients with upper lobe lesions, calcified adenopathy and old
      pleural thickening were considered reactivation forms. RESULTS: Of the 129
      patients (mean age, 31 +/- 18 years), 76% had primary TP and 24% reactivation TP.
      Differences were found in age (28 +/- 17 vs 40 +/- 18 years, P < 0.01), smoking
      (43% vs 74%, P < 0.01) and alcohol abuse (23% vs 47%, P < 0.05), weight loss (29%
      vs 50%, P < 0.05), positive sputum smears and cultures (2% vs 16%, 7% vs 28%, P <
      0.01), and number of large effusions (46% vs 26%, P < 0.05), but not in
      tuberculin reactivity, pleural fluid findings, positive pleural cultures, or
      presence of pleural granuloma. CONCLUSION: In our setting, TP predominantly
      affects young adults. Clinical, immunological, and pleural findings are similar
      to those of patients with classic symptoms of TP. Older age, smoking and alcohol
      abuse, smaller effusions and sputum yield are differential characteristics of
      reactivation forms.

PMID- 9626611
TI  - Epidemiology of Mycobacterium tuberculosis strains in San Francisco that do not
      contain IS6110.
AB  - IS6110 is commonly used as the basis for molecular epidemiologic and diagnostic
      studies of Mycobacterium tuberculosis. However, strains that do not contain
      IS6110 have been reported. If common, such strains would pose a limitation for
      molecular studies of M. tuberculosis. Analysis of a population-based sample from
      San Francisco of 1569 specimens submitted for fingerprinting demonstrated that
      the proportion of strains that lack IS6110 is less than 1%. While this low
      percentage permits IS6110 fingerprinting in San Francisco, it may be problematic
      in other settings.

PMID- 9626612
TI  - Viability of mycobacteria in formalin-fixed tissues.

PMID- 9626613
TI  - Detection of anti-LAM antibodies for the diagnosis of active tuberculosis.

PMID- 9626614
TI  - Weight as a surrogate marker of treatment response in tuberculosis.

PMID- 9626615
TI  - Accreditation across borders: the introduction of Joint Commission accreditation
      in Spain.
AB  - BACKGROUND: Introducing accreditation as conducted by the Joint Commission on
      Accreditation of Healthcare Organizations (Oakbrook Terrace, III) into Spain has
      raised many issues regarding the internationalization of accreditation.
      CHARACTERISTICS OF ACCREDITATION: In recent years more and more countries have
      considered accreditation a useful tool for the improvement of health care
      quality. In spite of the differences in the health care systems of the countries
      where accreditation has been introduced, many of the original characteristics of
      accreditation as seen in the United States largely remain: peer review
      evaluation, support of professional associations, voluntary participation, and a
      national approach. These similarities reflect the fact that the majority of the
      programs are based on models created by the Joint Commission. THE EXPERIENCE OF
      THE AVEDIS DONABEDIAN FOUNDATION: In 1994 the Avedis Donabedian Foundation (FAD),
      a nonprofit organization founded in Barcelona in 1988, broadened its scope to
      include accreditation. Having rejected the idea of creating de novo its own
      standards and accreditation program, FAD worked out an agreement with the Joint
      Commission whereby FAD would become a Spanish accrediting body to accredit
      Spanish hospitals but would collaborate with Joint Commission International to
      adopt the Joint Commission's accreditation standards and processes. DISCUSSION:
      The development of accreditation continues. As of spring 1998, seven hospitals
      and two ambulatory care centers are preparing for accreditation. FAD's experience
      with adapting the Joint Commission model of accreditation should be instructive
      to other countries considering health care accreditation.

PMID- 9626616
TI  - The Polish experience of quality improvement in primary care.
AB  - THE POLISH HEALTH CARE SYSTEM: The health care system in Poland is based on a
      model typical of east-central European countries, with features such as state
      owned health care organizations, centralized management and administration, and
      primacy of access to care over quality. Poorly planned and uncoordinated reforms
      have been undertaken to transfer some of the authority for health service
      management to local governments. PRIMARY HEALTH CARE IN POLAND: The reform of the
      health care system entails substitution of family physician-based for medical
      specialist-based primary care. Newly trained family physicians, as the first to
      start private surgery clinics financed from public sources, are the forerunners
      of the comprehensive reform and property structure transformation. MAKING THE
      TRANSITION FROM QUALITY ASSURANCE TO QUALITY IMPROVEMENT: Since the early 1990s,
      more and more organizations, individuals, and professional groups have begun to
      perceive health care regulations and other external control mechanisms as
      ineffective. Attempts have been made to replace periodic, restrictive activities
      with systematic continuous quality improvement efforts. Systems of voluntary
      accreditation are being developed and fostered. Groups have started meeting to
      develop medical practice guidelines and conduct peer review. Concern about
      quality of health care services is now reflected in the Polish legislation for
      the first time, as well as in numerous local and nationwide projects and
      publications. CONCLUSION: Despite some successes, the pioneers of quality
      improvement (QI) still have a long way to go. Continuation of educational
      activities and creation of a system of motivation for the development, of QI in
      primary care should be prioritized and encouraged.

PMID- 9626617
TI  - Quality management in medical specialties: the use of channels and dikes in
      improving health care in The Netherlands.
AB  - BACKGROUND: In 1989 a Dutch national policy was instituted to ensure that quality
      management is the responsibility of both health care professionals and
      management, with input from insurers and patients. In turn, quality management of
      medical specialists remained to a large extent self-regulatory, with
      accountability toward third-party payers and patients. Three programs for quality
      management-peer review, guidelines, and visitation-have sufficiently persuaded
      patient organizations and care insurers about medical specialists' ability to
      ensure the quality of the care they provide. PEER REVIEW: Operational since 1976,
      the national program for peer review in hospitals has stressed the need for
      explicit evaluative mechanisms. This program led to the foundation of the
      National Organization for Quality Assurance in Hospitals (CBO), which conducts
      peer review activities but also support efforts aimed at quality assurance in
      hospitals. Once it is linked with the other two quality management programs, peer
      review will realize its full potential as a profession-based method for
      standardizing and rationalizing medical specialty practice. PRACTICE GUIDELINES:
      Since 1982, more than 60 consensus guidelines have been developed for and by
      medical professionals, with input from patient organizations and third-party
      payers. Medical specialty associations have also created their own guidelines.
      Although the guidelines' impact has not been evaluated systematically, studies
      have shown effects on behavioral change and health outcomes. Solid, credible
      guidelines continue to be developed, although the successful implementation of
      these guidelines needs to be studied. VISITATION PROGRAM: Visitation, or onsite
      assessment of specialty practice sites (in training and non-training hospitals),
      has been a hot issue in Dutch medical quality assurance. All 28 scientific
      societies have visitation programs, focusing on areas for improvement such as
      process management, use of guidelines, and evaluation of patient satisfaction and
      treatment outcomes. Closely linked to other medical quality assurance activities,
      visitation programs also incorporate clinical guidelines into evaluations.
      CONCLUSIONS: Profession-driven peer review, practice guidelines, and visitation
      programs have been effective support tools for quality management in The
      Netherlands. Future challenges involve creating more synergy among these programs
      and between the profession-based quality management approaches and recently
      introduced hospital-based quality systems and maintaining the trust between third
      party payers and patients.

PMID- 9626618
TI  - Health care reform and quality initiatives in Brazil.
AB  - BACKGROUND: The pursuit of equity in health care and universal entitlement to
      access of services, as health care reform concerns, were addressed at a Brazilian
      national health conference in 1986, in a new constitution in 1988, and in
      subsequent legislative and administrative actions. However, in the early 1990s,
      economic policies affected the federal government's ability to fund the necessary
      services. QUALITY IMPROVEMENT (QI): In 1994 the Ministry of Health introduced a
      formal QI program, whose main purpose was to disseminate a culture of QI among
      health care providers, payers, and users of health services. The minister of
      health then established a national commission on QI, which played an important
      role in making QI activities an important activity. A NATIONAL ACCREDITATION
      PROGRAM: Efforts to create an accreditation program began in 1986. Since 1994
      work has proceeded on organization of a nongovernmental accreditation agency,
      development of national standards and procedures for the accreditation of health
      services, and dissemination of methods and procedures for health care quality
      management. QI PROGRAMS: Examples of QI programs that have been successfully
      implemented include those at the State of Rio de Janeiro Blood Center and the
      National Institute of Cancer. Since 1996, many national societies have begun to
      produce consensus statements and guidelines. Progress has also been made in
      consumer rights and protection. CONCLUSIONS: The public, health care
      professionals, providers, and the government are increasingly aware of the need
      to strengthen and develop QI initiatives for health care in Brazil. Awareness of
      the opportunities for improvements in health care which outcomes trigger should
      help contribute to their application.

PMID- 9626619
TI  - Quality improvement and the integrated management of childhood illness: lessons
      from developed countries.
AB  - BACKGROUND: The World Health Organization (WHO) and the United Nations Children's
      Fund have launched a global initiative to reform the health care received by sick
      children in developing countries. The core of this initiative, known as
      Integrated Management of Childhood Illness (IMCI), is a clinical practice
      guideline. The guideline addresses the case management of clinically ill children
      under the conditions typical of peripheral facilities, focusing on the most
      common serious conditions, such as pneumonia and malaria. WHO estimates that up
      to 70% of childhood deaths in developing countries are attributable to conditions
      addressed by IMCI. About 40 developing countries have made commitments to
      implementing IMCI in public-sector programs. QI STRATEGIES AND GUIDELINES IN
      DEVELOPING COUNTRIES: Like other clinical guidelines, which are increasingly
      accepted in developing countries' health programs, IMCI raises difficult quality
      issues. High levels of guideline compliance are needed for IMCI to be effective.
      However, many developing countries have achieved relatively low levels of
      compliance with far simpler guidelines, such as those for diarrhea case
      management. Despite obvious differences, the experience of developed countries in
      quality improvement (QI) offers a wide range of promising strategies for IMCI,
      including (1) developing standards, (2) communicating those standards to
      providers, (3) monitoring quality and providing feedback, (4) team-based QI
      problem solving, (5) designing processes conducive to high levels of quality, and
      (6) regulating providers and institutions. MORE LESSONS FROM DEVELOPED COUNTRIES
      FOR IMCI: Only recently have QI strategies been adapted for use in developing
      countries, and virtually none of the early experience has dealt with IMCI.
      Indirect evidence suggests that a wide range of QI approaches will prove suitable
      for IMCI. However, it will be important to carefully evaluate the cost
      effectiveness of early applications. The experience of developed countries also
      provides useful models for important issues that have not yet been addressed by
      the IMCI initiative. These issues include (1) the review and possible
      modification of the current guideline, (2) extending IMCI into the private sector
      through regulatory strategies, and (3) institutionalizing QI.

PMID- 9626620
TI  - Can Western quality improvement methods transform the Russian health care system?
AB  - BACKGROUND: The Russian health care system largely remains the same system that
      was in place during the existence of the Soviet Union. It is almost entirely
      state owned and operated, although ownership and management have developed from
      the central government to the oblast (province). The ZdravReform (Health Reform)
      Program (ZRP) in Russia, which began in 1993, included the goal of improving the
      quality and cost-effectiveness of the health care system. Work on introducing
      continuous quality improvement (CQI), evidence-based practice guidelines, and
      indicators of quality was conducted in 1995-1996. INTRODUCING EVIDENCE-BASED
      MEDICINE: As a result of the poor quality of Russian-language medical journals
      and the inability to gain access to the knowledge available in Western medical
      literature, Russian medical practices have not kept up with the rapid evolution
      of evidence-based medical practice that has begun transforming Western medicine.
      A number of evidence-based clinical practice guidelines were translated and
      disseminated to Russian-speaking physicians working in facilities participating
      in ZRP in Russia and Central Asia. DEVELOPING INDICATORS OF QUALITY OF CARE:
      Given the limitations of existing measures of the quality of care, indicators
      were developed for participating ambulatory polyclinics in several oblasts in
      Siberia. Russian physicians responsible for quality of care for their respective
      oblasts formed a working group to develop the indicators. A clinical information
      system that would provide automated collection and analysis of the indicator data
      as well as additional patient record information-was also developed. EXAMPLES OF
      CLINICAL QI WORK IN SIBERIA: CQI activities, entailing a multidisciplinary,
      participatory team approach, were conducted in four oblasts in western Siberia.
      Projects addressed the management of community-acquired pneumonia and reduction
      of length of stay after myocardial infarction (MI). One of the oblasts provided
      an example of a home-grown evidence-based protocol for post-MI care, which was
      adopted in the other three oblasts. LESSONS FROM THE RUSSIAN EXPERIENCE: Evidence
      based medicine is critically needed to improve the quality of research and
      publications, medical education, and medical practice. Physicians everywhere are
      data driven; they change their practices when convinced by good data. The key to
      successful introduction of evidence-based medicine is understanding the
      fundamentals of good scientific method as applied to medicine. The Russian health
      care system's experience in reporting to higher authorities' process and outcomes
      data that resemble our modern indicators can provide the basis for accurate and
      valid measures of quality. CONCLUSIONS: In contrast with American expectations
      that a significant cultural change in an organization could take years, even with
      great effort, Russian physicians and other clinicians rapidly assimilated the new
      concepts of QI and put them to use. More on-site assistance by international
      medical consultants will still be needed for several years to hasten the process
      of change and ensure that it does not become stalled.

PMID- 9626621
TI  - Paget's disease of bone: evidence for a susceptibility locus on chromosome 18q
      and for genetic heterogeneity.
AB  - Paget's disease of bone is a common condition characterized by bone pain,
      deformity, pathological fracture, and an increased incidence of osteosarcoma.
      Genetic factors play a role in the pathogenesis of Paget's disease but the
      molecular basis of the disease remains unclear. Previous genetic linkage studies
      have mapped the rare Paget's disease-like bone dysplasia familial expansile
      osteolysis (FEO) to chromosome 18q21-22, and recent work has shown evidence of
      linkage between this locus and Paget's disease in one family. Here we studied the
      relationship between the 18q21-22 locus and Paget's disease in eight large
      multiplex families from diverse ethnic backgrounds with inherited Paget's
      disease. Paget's disease was inherited as an autosomal dominant trait in all
      families, with high penetrance by the sixth decade. Analysis of seven highly
      polymorphic markers from chromosome 18q21-22 showed positive summated two-point
      log10 odds ratio (lodscores) of +2.97 with the marker D18S42 at a recombination
      fraction (theta) = 0.05, and of +2.95 with the marker D18S60 at theta = 0.00,
      values which are close to the cut-off of +3.0, which is generally accepted as
      evidence of linkage. Segregation analysis of the haplotypes and formal
      statistical analysis using the HOMOG program provided evidence for genetic
      heterogeneity, however, with evidence for linkage in five families and against
      linkage in the remaining three families (chi square 8.82; df = 2; p < 0.025).
      Multipoint linkage analysis in the five linked families showed lodscores of above
      +3.5 across the whole susceptibility region and a maximum summated lodscore of
      3.89 at the marker D18S465. In the three nonlinked families, negative multipoint
      results were obtained for the whole region, with lodscores below -2.0 in one
      family, excluding this as a candidate locus for the disease. Our studies
      demonstrate the importance of hereditary factors in the pathogenesis of Paget's
      disease and confirm evidence of linkage between Paget's disease and chromosome
      18q21-22 in some families. This raises the possibility that Paget's disease and
      FEO may share a common molecular basis, perhaps due to different mutations in the
      same gene or family of genes. Data from three families did not support evidence
      of linkage to 18q21-22 however, indicating that Paget's disease is genetically
      heterogeneous and suggests the presence of at least one additional locus which
      remains to be discovered.

PMID- 9626622
TI  - Risk factors for hip fracture in white men: the NHANES I Epidemiologic Follow-up
      Study.
AB  - This prospective population-based study assessed predictors of hip fracture risk
      in white men. Participants were members of the Epidemiologic Follow-up Study
      cohort of the First National Health and Nutrition Examination Survey, a
      nationally representative sample of noninstitutionalized civilians who were
      followed for a maximum of 22 years. A cohort of 2879 white men (2249 in the
      nutrition and weight-loss subsample, 1437 in the bone density subsample) aged 45
      74 years at baseline (1971-1975) were observed through 1992. Ninety-four percent
      of the original cohort were successfully traced. Hospital records and death
      certificates were used to identify a total of 71 hip fracture cases (61 in the
      nutrition and weight-loss subsample, 26 in the bone-density subsample). Among the
      factors evaluated were age at baseline, previous fractures other than hip, body
      mass index, smoking status, alcohol consumption, nonrecreational physical
      activity, weight loss from maximum, calcium intake, number of calories, protein
      consumption, chronic disease prevalence, and phalangeal bone density. The risk
      adjusted relative risk (RR) of hip fracture was significantly associated with
      presence of one or more chronic conditions (RR = 1.91, 95% confidence interval
      [CI] = 1.19-3.06), weight loss from maximum > or = 10% (RR = 2.27, 95% CI 1.13
      4.59), and 1 SD change in phalangeal bone density (RR = 1.73, 95% CI 1.11-2.68).
      No other variables were significantly related to hip fracture risk. Although
      based on a small number of cases, this is one of the first prospective studies to
      relate weight loss and bone density to hip fracture risk in men.

PMID- 9626623
TI  - Vitamin D receptor gene start codon polymorphisms (FokI) and bone mineral
      density: interaction with age, dietary calcium, and 3'-end region polymorphisms.
AB  - Osteoporosis is a polygenic disease, whose determining loci have not yet been
      identified. Vitamin D receptor (VDR) gene polymorphisms in the 3'-end region (as
      determined by the enzymes BsmI and ApaI) have been inconsistently associated with
      bone mineral mass. More recently, VDR start codon polymorphisms (as determined by
      the enzyme FokI) have been found to be related to adult bone mineral density
      (BMD) in pre- and postmenopausal American women. We investigated the association
      between BMD and FokI genotypes in premenopausal European-Caucasian women as well
      as in prepubertal girls from the same genetic background and examined the
      interaction with VDR 3'-end region polymorphisms and with dietary calcium intake.
      Areal BMD (g/cm2) was measured by dual-energy X-ray absorptiometry at the level
      of the lumbar spine, femoral neck, and femoral shaft in 177 healthy premenopausal
      women (age range, 18.7-56.0 years) as well as in 155 prepubertal girls (age
      range, 6.6-11.4 years). Genotyping for FokI, BsmI, and ApaI VDR polymorphisms was
      performed using polymerase chain reaction methods. FokI genotype-dietary calcium
      interaction was cross-sectionally analyzed in all subjects and longitudinally in
      103 prepubertal girls enrolled in a calcium intervention trial. The prevalence of
      FokI VDR gene polymorphisms in this cohort was 15% for ff, 50% for Ff, and 35%
      for FF. In the whole cohort of premenopausal women or prepubertal girls, no
      significant association was found between FokI VDR gene polymorphisms and BMD,
      even adjusted for age (Z score), weight, height, and calcium intake. Further
      analysis of FokI VDR gene polymorphisms and dietary calcium intake suggested a
      possible interaction in BMD determination, since a trend for an association with
      FokI genotypes was more evident at high than low calcium intake in both cross
      sectional and longitudinal studies. Furthermore, cross-genotyping FokI and either
      BsmI or ApaI VDR polymorphisms suggested that the ff genotype was associated with
      a significantly lower lumbar spine BMD in bb and aa prepubertal girls. FokI VDR
      gene polymorphisms were not significantly associated with BMD in healthy European
      Caucasian females. However, cross-genotyping of the VDR 3'-end and start codon
      polymorphic regions may provide a further insight into the complex determination
      of BMD.

PMID- 9626624
TI  - Bone morphogenetic proteins and bFGF exert opposing regulatory effects on PTHrP
      expression and inorganic pyrophosphate elaboration in immortalized murine
      endochondral hypertrophic chondrocytes (MCT cells).
AB  - A fundamental question in endochondral development is why the expression of
      parathyroid hormone-related protein (PTHrP), which inhibits chondrocyte
      maturation and mineralization, becomes attenuated at the stage of chondrocyte
      hypertrophy. To address this question, we used clonal, phenotypically stable SV40
      immortalized murine endochondral chondrocytes that express a growth-arrested
      hypertrophic phenotype in culture (MCT cells). Addition of individual cytokines
      to the medium of MCT cells revealed that bone morphogenetic protein (BMP)-6,
      which commits chondrocytes to hypertrophy, markedly inhibited PTHrP production.
      This activity was shared by three other osteogenic bone morphogenetic proteins
      (BMP-2, BMP-4, and BMP-7) and by transforming growth factor beta (TGF-beta),
      which all inhibited the level of PTHrP mRNA. In contrast, basic fibroblast growth
      factor (bFGF), an inhibitor of chondrocyte maturation to hypertrophy, induced
      PTHrP in MCT cells and antagonized the effects of BMP-2, BMP-4, BMP-6, and BMP-7
      and TGF-beta on PTHrP expression. Opposing effects of bFGF and BMPs also were
      exerted on the elaboration of inorganic pyrophosphatase (PPi), which regulates
      the ability of hypertrophic chondrocytes to mineralize the matrix. Specifically,
      BMP-2 and BMP-4, but not BMP-6 and BMP-7, shared the ability of TGF-beta to
      induce PPi release, and this activity was inhibited by bFGF in MCT cells. Our
      results suggest that effects on PTHrP expression could contribute to the ability
      of BMP-6 to promote chondrocyte maturation. BMPs and bFGF exert opposing effects
      on more than one function in immortalized hypertrophic chondrocytes. Thus, the
      normal decrease in bFGF responsiveness that accompanies chondrocyte hypertrophy
      may function in part by removing the potential for bFGF to induce PTHrP
      expression and to oppose the effects of BMPs. MCT cells may be useful in further
      understanding the mechanisms regulating the differentiation and function of
      hypertrophic chondrocytes.

PMID- 9626625
TI  - Recombinant human basic fibroblast growth factor accelerates fracture healing by
      enhancing callus remodeling in experimental dog tibial fracture.
AB  - Effect of recombinant human basic fibroblast growth factor (bFGF) on fracture
      healing was investigated using a tibial fracture in beagle dogs. Transverse
      fractures in the middle of the diaphyses were created in the right tibiae and
      bFGF was injected into the fracture sites at a single dose of 200 micrograms. The
      time course of changes in callus volume and morphology of the fracture sites were
      evaluated at weeks 2, 4, 8, 16, and 32 after treatment, and the fracture strength
      was analyzed at weeks 16 and 32. At week 2, a radiogram of the fracture site
      showed obvious membranous ossification in the group injected with bFGF. Basic FGF
      extended the callus area at week 4 and increased the bone mineral content (BMC)
      in the callus at week 8. bFGF also increased the osteoclast number in the
      periosteal callus at weeks 2 and 4. In the bFGF group, a maximal increase in the
      osteoclast index was found at week 4, and an identical increase was recognized in
      the control group at weeks 8 and 16. These findings strongly suggested that bFGF
      stimulated not only callus formation but osteoclastic callus resorption. BMC in
      the bFGF group was followed by a rapid decrease from week 8, while that in the
      control group was identical from week 4. Fracture strength of the bFGF group
      showed significant recovery by week 16, and recovery was still evident by week
      32. We conclude that bFGF promotes the fracture healing in dogs by the
      stimulation of bone remodeling.

PMID- 9626626
TI  - Initiation of the bony epiphysis in long bones: chronology of interactions
      between the vascular system and the chondrocytes.
AB  - Many events occur concurrently during the initiation of the secondary
      ossification center in the cartilaginous epiphyses of long bones. We have
      investigated the chronology of interactions between the vascular system and
      epiphyseal chondrocytes by culturing explanted heads of femurs and humeri from
      pre- and neonatal rabbits on the chorioallantoic membrane (CAM) of growing chick
      embryos. We confirmed that, on the whole, the epiphyseal cartilage was resistant
      to vascular invasion, whereas the physeal growth plate was resorbed. However, new
      CAM-derived cartilage canals occasionally penetrated through the articular
      surface. This caused death of those chondrocytes in the immediate vicinity of the
      canal but no further reaction. If explants already contained a bony epiphysis and
      were halved prior to culture, CAM-derived vessels were attracted to the
      spongiosa. From there they pushed into the uncalcified cartilage, indicating that
      calcification was not a prerequisite for vascular invasion. Where at least two
      vessels were in apposition, a new pseudo-ossification center was initiated:
      chondrocytes became hypertrophic and the matrix calcified. This suggests that
      cumulative release of diffusible factors from more than one vessel was the
      trigger for chondrocyte hypertrophy, which, in turn, led to the initiation of the
      bony epiphysis. CAM cultures thus provide an experimental model for both the
      quiescent angiogenesis of cartilage canal formation and the reactionary
      angiogenesis associated with chondrocyte hypertrophy. By exploiting the different
      anatomy of CAM-derived vascularity, events that occur concurrently in vivo can be
      specially separated in CAM culture.

PMID- 9626627
TI  - Influence of aluminum on the regulation of PTH- and 1,25(OH)2D3-dependent
      pathways in the rat osteosarcoma cell line ROS 17/2.8.
AB  - The role of hormonal status in the development of aluminum (Al)-dependent renal
      osteodystrophy, which is characterized by reduced bone matrix deposition, still
      remains largely unknown. To address this question, we used the osteoblast-like
      osteosarcoma cell line ROS 17/2.8 to evaluate the role of Al on parathyroid
      hormone (PTH)- and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)-dependent activities in
      these cells. Al (1 microM) caused an inhibition of basal and 1,25(OH)2D3-induced
      alkaline phosphatase, but only at low doses (< 1 nM) of the steroid. Al partly
      inhibited basal osteocalcin (OC) secretion in ROS cells (p < 0.001), and the dose
      dependent increase in 1,25(OH)2D3-induced OC release by these cells was also
      reduced by 1 microM Al at low concentrations of the steroid (< or = 1 nM),
      whereas high doses of 1,25(OH)2D3 (> or = 5 nM) totally prevented the inhibiting
      effects of Al. Al also had strong inhibitory actions on PTH-dependent cAMP
      production by ROS cells over the concentration range tested (0.5-50 nM). This
      inhibitory action of Al was also observed for PTH-related peptide- (PTHrp, 50 nM)
      but not for Isoproterenol-dependent (100 nM) cAMP formation. To evaluate more
      fully the mechanism of this inhibition of cAMP formation, we investigated the
      effect of Al on toxin-modulated, G protein-dependent regulation of cAMP formation
      and on the activation of adenylate cyclase by Forskolin. Cholera toxin (CT, 10
      micrograms/ml), applied to cells for 4 h prior to PTH challenge, enhanced cAMP
      production about 2-fold above PTH alone (p < 0.001), a process that was further
      stimulated by Al. Pertussis toxin (PT, 1 microgram/ml, 4 h) did not modify basal
      PTH-dependent cAMP formation by ROS cells. However, PT treatment prevented the
      inhibitory effect of Al on cAMP formation by these cells (p < 0.025). The
      stimulation of adenylate cyclase by Forskolin (0.1 and 1 microM), which bypasses
      G protein regulation, was not modified by Al, indicating that Al does not affect
      adenylate cyclase directly. Northern blot analysis of PTH receptor mRNA levels
      showed that Al did not modify PTH receptor message in ROS cells. Likewise,
      Western blot analyses of G protein subunits showed that Al did not significantly
      alter Gs alpha subunit levels, in accordance with the results obtained for cAMP
      dependent formation in response to CT. In contrast, Gi alpha-1 and Gi alpha-2
      subunits were decreased by Al treatment, consistent with PT-restricted increases
      in cAMP formation in Al-treated ROS cells. Taken together, these results suggest
      that Al has multiple actions in osteoblast-like ROS cells. The effects of Al are
      modulated by hormonal control of the pathways investigated. Al affects
      1,25(OH)2D3-regulated functions only when this steroid is low. Al has large
      inhibitory effects on PTH- and PTHrp-dependent cAMP formation. This last feature
      is related to the ability of Al to alter the G protein transducing pathway for
      PTH/PTHrp-dependent formation of cAMP since it does not affect adenylate cyclase
      activity directly and does not affect the PTH receptor message level. Thus, Al
      has stronger deleterious effects in osteoblast-like cells with an already
      compromised 1,25(OH)2D3 status and can modulate specifically PTH/PTHrp-mediated
      cAMP formation at the postreceptor level.

PMID- 9626628
TI  - Osteoclast differentiation requires ascorbic acid.
AB  - Osteoclast differentiation assays are usually conducted in alpha minimal
      essential medium (alpha-MEM). We reasoned that determining which components of
      this media are critical for osteoclast differentiation might provide insight into
      the mechanisms that regulate osteoclast differentiation. This study demonstrates
      that ascorbic acid is the crucial component of alpha-MEM that stimulates
      differentiation of murine osteoclasts in cocultures with murine mesenchymal
      support cells. Thus, supplementation with ascorbic acid allows osteoclast
      differentiation to occur in basal MEM media as well as in RPMI-1640 and basal
      media Eagle (BME) media. The conclusion that osteoclast differentiation is
      stimulated by ascorbic acid was obtained whether osteoclast differentiation was
      induced by 1,25-dihydroxyvitamin D3 or parathyroid hormone, whether ST2 or CIMC-2
      cells were used as mesenchymal support cells, and whether osteoclast precursors
      were obtained from spleen or bone marrow. Time course studies revealed that
      although ascorbic acid only modestly increases the rate at which osteoclast
      precursors begin to express tartrate-resistant acid phosphatase, it strongly
      increases the rate at which precursors fuse into mature, multinucleated cells.
      Moreover, ascorbic acid strongly increases the life span of both osteoclasts and
      their precursors. The increases in precursor formation, fusion, and life span
      induced by ascorbic acid are together responsible for the stimulation of
      osteoclast differentiation by ascorbic acid. Given the known effects of ascorbic
      acid on differentiation of mesenchymal cells, it may stimulate osteoclast
      differentiation indirectly by regulating the differentiation state of the
      mesenchymal cells that support osteoclast differentiation.

PMID- 9626629
TI  - Fractal dimension as a measure of altered trabecular bone in experimental
      inflammatory arthritis.
AB  - Our previous studies in experimental inflammatory arthritis (EIA) and in human
      rheumatoid arthritis demonstrated rapid remodeling with a 5-fold increase in bone
      resorption and bone formation. Normal condylar trabecular bone is typically
      anisotropic, with its orientation along lines of stress; rapid remodeling in a
      pathological state could disturb the usual order of trabeculae. This study
      assessed change in the structure of trabecular bone of the distal femoral
      epiphysis after induction of EIA, using a measure of "fractal dimension," which
      may be considered a quantitative description of the degree of irregularity of
      complex surfaces. Data was obtained from specimens in which EIA had been induced
      in the rabbit knee by 10 injections of carrageenan over 49 days. Photographic
      enlargements of embedded undecalcified cross-sections of the distal femur were
      digitized, and software written on a Sun workstation was used to define
      repeatable regions of interest (ROIs) in the images. The ROIs were subjected to
      fractal analysis by a power law method. The fractal dimension of the trabecular
      bone pattern within the ROI was estimated by fitting an equation of the form A
      (epsilon) = lambda epsilon (2-D) to the data. In this equation, A (epsilon) is
      the area of the "surface" formed by modeling the ROI data as a three-dimensional
      structure with the grey-level magnitude providing the third dimension, lambda is
      a scaling constant, epsilon is the size of the measuring "tool" used to measure
      the area, and D is the fractal dimension. A Mann-Whitney U-test applied to the
      average of the data from all ROIs showed that the two distributions of fractal
      dimension were significantly different (p < 0.005). There were only two overlaps
      between data points for arthritis (with these values higher) and normal groups (n
      = 11 for each group). Since Howship's lacunae were too small to be resolved in
      the system utilized, we consider the difference in fractal dimension to be
      primarily related to trabecular surface orientation, rather than to the increased
      number of asperities (resorptive foci) occurring due to increased turnover in
      bone affected by inflammatory arthritis. The results suggest that fractal
      dimension may be a useful tool for assessing the degree of structural damage to
      trabeculae in conditions similar to EIA.

PMID- 9626630
TI  - A third-generation bisphosphonate, YM175, inhibits osteoclast formation in murine
      cocultures by inhibiting proliferation of precursor cells via supporting cell
      dependent mechanisms.
AB  - The theory that bisphosphonates inhibit osteoclast formation through their
      effects on osteoblastic cells remains controversial. To confirm the inhibitory
      effect of bisphosphonates on osteoclast formation and gain some insights into the
      underlying mechanisms, we examined the effect of disodium dihydrogen
      (cycloheptylamino)-methylene-bisphosphonate monohydrate (YM175) on osteoclast
      like multinucleated cell (OCL) formation in various mouse coculture systems. When
      different origins of osteoclast precursors (bone marrow, spleen, or nonspecific
      esterase-positive cells) were cocultured with the same supporting cells
      (calvarial osteoblasts), YM175 inhibited OCL formation similarly in all cultures.
      When the same osteoclast precursors (spleen cells) were cocultured with
      supporting cells of different origin, the results were variable. YM175 inhibited
      OCL formation almost completely in cocultures with calvarial osteoblasts or
      osteoblastic cell line KS4, while it did not, or only slightly, inhibit OCL
      formation in cocultures with stromal cell lines, ST2 or MC3T3-G2/PA6. Temporal
      addition of YM175 in cocultures of spleen cells with osteoblastic cells revealed
      that YM175 was effective when it was present at an early phase of the culture
      period. Consistent with this observation, YM175 in the presence of osteoblastic
      cells inhibited proliferation of preosteoclastic cells, but did not inhibit the
      fusion of mononuclear prefusion osteoclasts. In conclusion, the inhibitory effect
      of YM175 on OCL formation was confirmed in various murine coculture systems, but
      the effect was dependent on the types of bone-derived cells supporting
      osteoclastogenesis. The findings suggest that YM175 inhibits osteoclastogenesis
      by inhibiting the proliferation of osteoclast precursors through its action on
      supporting cells of osteoblast lineage rather than acting directly on osteoclast
      precursors.

PMID- 9626632
TI  - The preventive and interventional effects of raloxifene analog (LY117018 HCL) on
      osteopenia in ovariectomized rats.
AB  - The effects of LY117018 HCL (LY) treatment on bone metabolism, spine bone mineral
      density (BMD), bone mineral content (BMC), and serum cholesterol were studied in
      ovariectomized (OVX) rats. Experiment 1 was designed to observe the preventive
      effects of LY on bone loss due to ovariectomy (OVX; prevention study). The rats
      were divided into three groups: sham group, OVX + vehicle, and OVX + LY. LY was
      administrated at the same time of OVX. Experiment 2 was designed to investigate
      the interventional effects of LY on OVX rats with osteopenia (intervention
      study). The rats were divided into the sham and OVX groups, first. The OVX rats
      were allowed to lose bone for 6 weeks. At 6 weeks post-OVX, the OVX rats were
      divided into two groups: OVX + vehicle and OVX + LY. The longitudinal effects of
      LY on bone were studied by dual-energy X-ray absorptiometry and biochemical
      markers including urinary pyridinoline (Pyr), deoxypyridinoline (Dpyr), and serum
      osteocalcin. Urinary Pyr and Dpyr increased maximally at 6 weeks post-OVX,
      decreased at 12 and 18 weeks post-OVX, although the OVX rats had significantly
      higher levels of Pyr and Dpyr than the sham group during the experiment. LY was a
      very potent inhibitor of Pyr and Dpyr excretion while at the same time only
      partially reducing the bone loss in the high turnover phase at 6 weeks
      postovariectomy. However, at the later time points at 12 and 18 weeks, no further
      bone loss occurred in rats treated with LY, while the vehicle-treated group lost
      another 10% in spine BMD and BMC. LY also completely blocked further bone loss
      when used in an intervention protocol. LY significantly reduced serum cholesterol
      levels in OVX rats. The results suggest that LY is not fully protective during
      the early rapid bone loss phase, but the compound is fully protective during the
      later slow phase of bone loss in both the protocols.

PMID- 9626631
TI  - Characterization of aromatase and 17 beta-hydroxysteroid dehydrogenase expression
      in rat osteoblastic cells.
AB  - Postmenopausal loss of 17 beta-estradiol (E2) in women is associated with
      decreased bone mineral density and increased susceptibility to osteoporotic bone
      fracture. These changes in bone status are assumed to be due to circulating
      levels of the hormone; therapeutic replacement of E2 can alleviate the bone
      disease. However, recent reports have shown that human osteoblastic (OB) cells
      are able to synthesize estrogens locally, via expression of the enzyme aromatase.
      In this study, we have characterized the expression and activity of aromatase and
      17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) in rat OB cell lines.
      Aromatase activity in ROS 17/2.8, ROS 25/1, and UMR 106 cells was similar to that
      shown in human OB cells, with the highest levels of activity observed in the more
      differentiated ROS 17/2.8 cells (Vmax = 45 pmol/h/mg of protein). The rat OB
      cells also showed 17 beta-HSD activity, with the predominant metabolism in all
      three cell lines being estrone (E1) to E2. As with aromatase, the highest
      activity was observed in ROS 17/2.8 cells (Vmax = 800 pmol/h/mg of protein).
      Northern analyses indicated the variable presence of transcripts corresponding to
      the type 1, 2, 3, and 4 isoforms of 17 beta-HSD. Further analysis of
      androstenedione metabolism indicated that the net effect of aromatase and 17 beta
      HSD activity varied with cell type and culture treatment. All three OB cell lines
      were able to synthesize E1, E2, and testosterone from androstenedione, although
      activity varied between OB cell types. Regulatory effects were observed with 1,25
      dihydroxyvitamin D3 (positive) and dexamethasone (negative). These data suggest
      that local synthesis of sex hormones is an important function of OB cells and may
      play a key role in the modulation of bone turnover independent of circulating
      hormone concentrations.

PMID- 9626633
TI  - Responses of trabecular and cortical bone turnover and bone mass and strength to
      bisphosphonate YH529 in ovariohysterectomized beagles with calcium restriction.
AB  - Thirty-six beagles, 18 months of age, underwent ovariohysterectomy (OHX) or a
      sham operation. Sham-operated animals were given a diet with standard calcium
      (1.4%) (group 1, n = 6) or a restricted calcium diet (0.14%) (group 2, n = 6).
      The OHX animals were given the restricted calcium diet and YH529 orally with
      respective daily doses of 0, 0.02, 0.1, and 0.5 mg/kg of body weight (groups 3-6,
      n = 6 each) for 12 months. At the end of this period, the lumbar bone mineral
      densities (BMDs) in groups 2 and 3 and the load values for group 3 were
      significantly smaller than those for group 1. The midfemur BMD did not differ
      among the groups. The urinary deoxypyridinoline (U-Dpy) and bone formation rates
      (BFR/BS, BFR/BV) in groups 2 and 3 and the osteonal BFR/BS and trabecular
      osteoclast number (Oc.N/BS) in group 3 were significantly larger than the
      respective values for group 1. However, these parameters did not significantly
      differ between groups 2 and 3. The serum osteocalcin (OC) level, wall thickness
      (W.Th), and mineral apposition rate values for group 3 were significantly larger
      than those for group 2. In group 2, the trabecular activation frequency (Ac.F)
      increased by 3.11 times, and the percent values of the number of labeled osteons
      (L-Ot.N/T-Ot.N, %) in the tibia by 3.28 times over those for group 1. In group 3,
      the Ac.F increased by 3.20 times and the number of labeled osteons by 3.77 times
      over those for group 1. In groups 4-6, the U-Dpy and Oc.N/BS values were smaller,
      but their OC levels did not significantly differ from the level for group 3. The
      lumbar BMD, the load, and W.Th were dose-dependently significantly larger than
      those for group 3. The Ac.F values were significantly smaller, and the respective
      value in groups 4-6 was 67.9, 25.5, and 10.2% of that in group 3. The BMDs of the
      midfemur in groups 4-6 were significantly larger than those in group 3, but the
      ultimate load values did not significantly differ. The L-Ot.N/T-Ot.N values were
      also significantly smaller, and the respective value in groups 4-6 was 82.0,
      48.5, and 55.2% of that in group 3. The tibial endocortical and periosteal
      BFR/BSs did not differ significantly. These data demonstrate that the effects of
      OHX on bone mass and turnover were small in the beagles fed a restricted calcium
      diet. YH529 maintained the mass and strength of the lumbar bone by reducing the
      bone resorption. The cortical bone appeared to be less sensitive to the agent
      than the trabecular bone in this animal model.

PMID- 9626634
TI  - Differential effects of estrogen metabolites on bone and reproductive tissues of
      ovariectomized rats.
AB  - The effects of 17 beta-estradiol and the important estrogen metabolites, 2
      hydroxyestrone (2-OHE1) and 16 alpha-hydroxyestrone (16 alpha-OHE1) on bone,
      mammary gland, and uterine histology, and on blood cholesterol were investigated
      in ovariectomized growing rats. Rats were treated with 200 micrograms/kg of body
      weight/day of each of the test compounds for 3 weeks. Ovariectomy resulted in
      uterine and mammary gland atrophy, increased body weight, bone turnover and tibia
      growth, and hypercholesterolemia. 17 beta-estradiol treatment prevented these
      changes, with the exception that this high dose of estrogen did not prevent
      hypercholesterolemia. 2-OHE1 had no effect on any of the measurements. 16 alpha
      OHE1 resulted in bone measurements that did not differ from the 17 beta-estradiol
      treated rats and prevented the increase in serum cholesterol. In contrast, 16
      alpha-OHE1 resulted in increases in uterine weight, uterine epithelial cell
      height, and mammary gland cell proliferation that were significantly less than
      the 17 beta-estradiol treatment. These findings demonstrate that 16 alpha
      hydroxylation of estrone results in tissue-selective estrogen agonistic activity,
      whereas 2-hydroxylation resulted in no measured activity. Furthermore, they
      suggest that factors that modulate the synthesis of these metabolites could
      selectively influence estrogen target tissues.

PMID- 9626635
TI  - Risedronate in the treatment of Paget's disease of bone: an open label,
      multicenter study.
AB  - An open-label, multicenter study was conducted to determine the efficacy and
      safety of oral risedronate (a pyridinyl bisphosphonate) in 162 patients (102 men,
      60 postmenopausal women; mean age, 68 years) with moderate to severe Paget's
      disease of bone (mean serum alkaline phosphatase [ALP] approximately seven times
      the upper limit of normal). Patients were treated with oral risedronate, 30
      mg/day for 84 days, followed by 112 days without treatment. This 196-day cycle
      was repeated once if serum ALP did not normalize or increased from the nadir
      value by > or = 25%. At the end of the first and second cycles, the mean
      percentage decreases for serum ALP were 65.7% and 69.1%, and for urinary
      hydroxyproline/creatinine 50.4% and 66.9%, respectively. The decreases from
      baseline in ALP and urinary hydroxyproline/creatinine were significant (p <
      0.001). Normalization of serum ALP was observed in 86 patients (53.8%): 53 during
      the first treatment cycle and 33 during the second. There was a significant
      proportion of patients reporting a decrease in the pagetic bone pain at days 84
      and 196 (p < 0.001). Overall, risedronate was well tolerated. Five patients
      withdrew due to adverse events, none of which were considered to be drug related.
      In conclusion, 30 mg of oral risedronate administered daily for 84 days
      significantly reduced the biochemical indices of disease activity and was
      associated with pain reduction in patients with moderate to severe Paget's
      disease of bone. Normalization of ALP was observed in the majority of patients.
      Repeated administration of risedronate was shown to be beneficial. In general,
      risedronate was well tolerated and demonstrated a good safety profile.

PMID- 9626636
TI  - Role of nitric oxide and prostaglandins in mechanically induced bone formation.
AB  - We have previously shown that prostaglandins (PG) and nitric oxide (NO) are
      required in the induction of bone formation by mechanical stimulation. We
      therefore tested the ability of NO donors, S-nitroso-N-acetyl-D,L-penicillamine
      (SNAP), and S-nitroso-glutathione (GSNO) to mimic or augment the osteogenic
      response of bone to a minimal mechanical stimulus. In rats administered vehicle
      or the vasodilator hydralazine, stimulation of the 8th caudal vertebra increased
      bone formation. In animals treated with SNAP or GSNO, there was significant
      potentiation of this osteogenic response. The bone formation rate in nonloaded
      vertebrae was unaffected by administration of the NO donors. We also found that
      while inhibition of either PG or NO production at the time of loading caused a
      partial suppression of c-fos mRNA expression in the loaded vertebrae,
      administration of indomethacin and NG-monomethyl-L-arginine together markedly
      suppressed c-fos expression. This suggests that although both PG and NO are
      required in mechanically induced osteogenesis, they appear to be generated
      largely independently of each other. Moreover, while exogenous NO potentiates the
      stimulatory effect of mechanical loading on bone formation, the lack of effect in
      nonloaded vertebrae suggests that NO is necessary but not sufficient for
      induction of bone formation.

PMID- 9626637
TI  - Calcium supplementation suppresses bone turnover during weight reduction in
      postmenopausal women.
AB  - Bone mobilization, lowering of bone mineral density (BMD), and osteoporotic
      fractures are recognized in postmenopausal women with weight loss. Because a high
      calcium intake suppresses bone loss in peri- and postmenopausal women, the
      present randomized, double-blind, placebo-controlled study was designed to test
      the hypothesis that calcium supplementation prevents net bone mobilization and
      consequent bone mineral loss during voluntary weight reduction in obese
      postmenopausal women. Subjects were placed on a moderate energy-restricted diet
      and either calcium supplementation (1 g/day) or placebo for 6 months. Body
      weight, bone turnover markers (pyridinium cross-links), osteocalcin, and
      parathyroid hormone (PTH) were measured at treatment weeks 1-5, 7, 10, 13, 16,
      20, and 25. Total body BMD, insulin-like growth factor, 25-hydroxyvitamin D, and
      sex hormone binding globulin (SHBG) were measured at baseline and week 25. The
      calcium supplemented (n = 15; age 60.9 +/- 9.4 years, body mass index [BMI] 33.2
      +/- 4.6 kg/m2) and placebo (n = 16; age 55.8 +/- 8.3 years, BMI 32.9 +/- 4.5
      kg/m2) groups lost similar amounts of weight over the study interval (10.2 +/-
      5.3% vs. 10.0 +/- 5.2%) and both groups increased SHBG (p < 0.001). There was a
      statistical effect of calcium supplementation during weight loss to suppress
      pyridinium cross-links, osteocalcin, and PTH (p < 0.05, < 0.01, and < 0.05,
      respectively). Loss of BMD tended to be greater in the placebo group by 1.4% (p <
      0.08) after weight loss. One gram per day calcium supplementation normalizes the
      increased calcium-PTH axis activity and the elevated bone turnover rate observed
      during moderate voluntary energy restriction in postmenopausal women.

PMID- 9626638
TI  - Alendronate does not block the anabolic effect of PTH in postmenopausal
      osteoporotic women.
AB  - In rodent osteoporosis models, anabolic activity of parathyroid hormone (PTH) is
      preserved in the presence of antiresorptive agents. Anabolic activity is also
      preserved when PTH is administered to estrogenized postmenopausal women. In
      contrast, in the ewe treated with tiludronate, PTH-induced stimulation of bone
      turnover did not occur. To determine whether PTH in combination with alendronate
      could be a viable treatment for osteoporosis, we performed a short-term study of
      postmenopausal women with osteoporosis (n = 10) already on alendronate 10 mg/day
      to determine whether PTH could increase bone formation assessed biochemically.
      Patients continued alendronate alone (n = 5) or continued alendronate with 400
      IU/day subcutaneous human PTH (1-34) added for 6 weeks. Subjects receiving PTH
      had serum and urine sampling weekly during PTH treatment and for 5 weeks
      thereafter. Sampling was performed approximately biweekly for subjects who had
      been on alendronate alone for 11 weeks. Samples were analyzed for osteocalcin
      (OC), propeptide of type I procollagen (PICP), bone-specific alkaline phosphatase
      (BSAP), cross-linked urinary N-telopeptide (NTX), and free urinary pyridinoline
      (PYD). Markers of bone formation increased within 3 weeks in the PTH plus
      alendronate group, with mean peak levels at 5-7 weeks: OC 49%, p < 0.01; PICP
      61%, p < 0.01; and BSAP 24%, p = 0.12. Levels returned to baseline after
      discontinuing PTH, with PICP declining the most rapidly. There were no
      significant changes at any time in the alendronate alone group. There were no
      increments in either urinary NTX or PYD in either treatment group throughout the
      observation period. The bone turnover marker changes seen with PTH plus
      alendronate were similar to those seen with PTH plus hormone replacement. These
      data suggest that: PTH can stimulate bone formation, evidenced by elevations of
      bone formation markers, even in the presence of a potent bisphosphonate; in the
      presence of alendronate, PTH-stimulated bone formation precedes stimulation of
      bone resorption, suggesting that PTH stimulates bone formation de novo; and the
      combination of PTH and alendronate may be a viable treatment option for
      postmenopausal women with osteoporosis.

PMID- 9626639
TI  - Congenital linear sebaceous nevus syndrome.

PMID- 9626640
TI  - Do different funding mechanisms produce different results? The implications of
      family planning for fiscal federalism.
AB  - The 104th Congress considered massive structural changes in federal aid to the
      states. Not only would federal categorical grants be consolidated into block
      grants, but entitlement programs would be converted to block grants too. Using
      family planning as a case study, this article examines whether program impacts
      change if different grant mechanisms are employed. Findings from a pooled time
      series analysis of state family planning expenditures show that categorical
      funding (here, title X of the Public Health Service Act) is the most cost
      effective in producing desired outcomes, such as lowering infant mortality.
      Policies using entitlement grants are generally more cost effective than those
      that rely upon block grants. We discuss the implications of these findings for
      health policy more broadly and for fiscal federalism in general.

PMID- 9626641
TI  - Does removing certificate-of-need regulations lead to a surge in health care
      spending?
AB  - This study assesses the impact of certificate-of-need (CON) regulation for
      hospitals on various measures of health spending per capita, hospital supply,
      diffusion of technology, and hospital industry organization. Using a time series
      cross-sectional methodology, we estimate the net impact of CON policies on costs,
      supply, technology diffusion, and industry organization, controlling for area
      characteristics, the presence of other forms of regulation, such as hospital rate
      setting, and competition. Mature CON programs are associated with a modest (5
      percent) long-term reduction in acute care spending per capita, but not with a
      significant reduction in total per capita spending. There is no evidence of a
      surge in acquisition of facilities or in costs following removal of CON
      regulations. Mature CON programs also result in a slight (2 percent) reduction in
      bed supply but higher costs per day and per admission, along with higher hospital
      profits. CON regulations generally have no detectable effect on diffusion of
      various hospital-based technologies. It is doubtful that CON regulations have had
      much effect on quality of care, positive or negative. Such regulations may have
      improved access, but there is little empirical evidence to document this.

PMID- 9626642
TI  - The economic returns to hospital admitting privileges.
AB  - Legal suits contesting the denial or termination of hospital staff privileges are
      the most common antitrust cases involving medical markets. There is, however,
      very little evidence about the economic implications for the physicians of having
      staff privileges. Using a nationally representative sample of self-employed
      physicians from 1992, this article presents estimates of the effects of hospital
      admitting privileges on physician earnings. The results indicate that for
      nonprimary care specialists with few admitting privileges, gaining an additional
      privilege increase earnings. This effect diminishes as the number of admitting
      privileges increases, however, and there are no economic gains beyond having
      three to four admitting privileges. Among primary care physicians, we detect no
      statistically significant effect of hospital admitting privileges on earnings.
      With the growing emphasis on managed care, physicians are being scrutinized both
      in terms of the quality of care they deliver and their impact on the economic
      performance of hospitals and managed care organizations. This suggests that the
      frequency of lawsuits involving the denial or rescission of medical staff
      privileges may assume even greater importance.

PMID- 9626643
TI  - An in-depth look at congressional committee jurisdictions surrounding health
      issues.
AB  - Congress plays an important role in shaping U.S. health care policy, and within
      Congress, committees play the lead policy-making role. To determine the range and
      extent of committee involvement on health issues, I examine nine health issue
      categories over a fifteen-year period (1979-1993) to discover how both
      "legislative" and "nonlegislative" committee jurisdictions differ across three
      dimensions: congressional chambers, committees within those chambers, and
      specific health issue categories. Then, to capture differences across a fourth
      dimension, time, I also calculate annual measures of jurisdiction "concentration"
      for legislative and nonlegislative jurisdictions. Together, the jurisdiction
      differences across the four dimensions provide a comprehensive view of
      congressional committee jurisdiction arrangements surrounding health issues. I
      find that the differences in jurisdiction across each dimension follow general
      patterns resulting from institution-specific factors (e.g., rules, norms) and
      from issue-specific factors (e.g., salience, complexity). Recognizing these
      dimensions and their respective patterns helps us understand the power that
      committees exercise over health issues.

PMID- 9626644
TI  - Forecasting American health care: how we got here and where we might be going.
AB  - This article is a form of thinking about the future properly regarded as
      conditional forecasting. It begins by reminding readers of the enormous changes
      in American medicine since World War II. The second part revisits critically an
      earlier effort at conditional forecasting for 1995 that Paul Starr and I
      published in the early 1980s. Besides reviewing the prescience of our forecasts,
      the second part outlines the earlier trends in progress we identified and the
      four combinations of political and economic settings we explored. On that basis,
      the final part takes up the challenge of anticipating sensibly some possible
      medical futures in the America of the early twenty-first century, a task which
      excludes simple extrapolation.

PMID- 9626645
TI  - The Medicare reforms of 1997: headlines you didn't read.
AB  - The 1997 Medicare reforms were among the most important social and health policy
      legislation of the past three decades. The legislation was notable in
      reestablishing a viable health policy process; in disproving predictions that
      government-run insurance would restrict consumer freedoms more than employer
      based health insurance; and in ratifying market-oriented approaches as a national
      health paradigm. Most important, the legislation achieved a historic
      philosophical compromise between advocates of government health insurance and
      advocates of private health insurance. The political agreements came at the
      expense of greater regulatory capture of the Medicare program by health provider
      and health plan interests and at the expense of deficient consumer protections.

PMID- 9626646
TI  - A link-segment model of upright human posture for analysis of head-trunk
      coordination.
AB  - Sensory-motor control of upright human posture may be organized in a top-down
      fashion such that certain head-trunk coordination strategies are employed to
      optimize visual and/or vestibular sensory inputs. Previous quantitative models of
      the biomechanics of human posture control have examined the simple case of ankle
      sway strategy, in which an inverted pendulum model is used, and the somewhat more
      complicated case of hip sway strategy, in which multisegment, articulated models
      are used. While these models can be used to quantify the gross dynamics of
      posture control, they are not sufficiently detailed to analyze head-trunk
      coordination strategies that may be crucial to understanding its underlying
      mechanisms. In this paper, we present a biomechanical model of upright human
      posture that extends an existing four mass, sagittal plane, link-segment model to
      a five mass model including an independent head link. The new model was developed
      to analyze segmental body movements during dynamic posturography experiments in
      order to study head-trunk coordination strategies and their influence on sensory
      inputs to balance control. It was designed specifically to analyze data collected
      on the EquiTest (NeuroCom International, Clackamas, OR) computerized dynamic
      posturography system, where the task of maintaining postural equilibrium may be
      challenged under conditions in which the visual surround, support surface, or
      both are in motion. The performance of the model was tested by comparing its
      estimated ground reaction forces to those measured directly by support surface
      force transducers. We conclude that this model will be a valuable analytical tool
      in the search for mechanisms of balance control.

PMID- 9626647
TI  - The effects of steroids on vestibular compensation and vestibular nucleus
      neuronal activity in the guinea pig.
AB  - Recent studies have suggested that steroids such as dexamethasone and
      methylprednisolone might be useful in the treatment of vestibular disorders,
      irrespective of whether inflammatory processes are involved. The aim of this
      study was to investigate the effects of systemic administration of dexamethasone
      on vestibular compensation of spontaneous nystagmus (SN) in guinea pig, and the
      effects of dexamethasone and methylprednisolone on extracellularly recorded
      spontaneous activity of medial vestibular nucleus (MVN) neurons in brainstem
      slices in vitro. In the behavioral study, none of the 3 doses of dexamethasone
      (5, 10, or 40 mg/kg i.p., delivered at 0, 12, 24, and 36 h following a unilateral
      surgical labyrinthectomy (UL)) resulted in a significant change in the frequency
      or compensation of SN, relative to the vehicle control group. In the in vitro
      study, only a minority of MVN neurons showed any response to 1 microM
      dexamethasone (1 out of 9 neurons), or 10 nM (3 out of 13), or 0.1 microM
      methylprednisolone (3 out of 7). These results suggest, contrary to previous
      evidence, that dexamethasone may not accelerate compensation of SN following
      surgical UL and that dexamethasone and methylprednisolone may have a direct
      action only on a minority of MVN neurons.

PMID- 9626648
TI  - Immunocytochemical localization of calmodulin in the vestibular end-organs of the
      gerbil.
AB  - This study demonstrates the presence of calmodulin in the vestibular end-organs
      of the gerbil by use of immunocytochemistry. Using fluorescence microscopy,
      calmodulin was localized to the cytoplasm, cuticular plate, and stereocilia of
      both type I and type II hair cells in the sensory epithelia of the utricle and
      cristae ampullaris; no label was found in the supporting cells, the dark cells,
      or the nerve fibers. There was no immunoreactive distinction between the labeling
      of type I and type II hair cells in the striolar or extrastriolar regions. Thus,
      immunocytochemical labeling for calmodulin provides a good marker for hair cells
      in gerbil vestibular epithelium. The presence of calmodulin in the stereocilia
      was confirmed by immunoelectron microscopy using secondary antibodies coupled to
      colloidal gold.

PMID- 9626649
TI  - The effect of space missions on gravity-responsive torsional eye movements.
AB  - Three astronauts underwent preflight, inflight, and postflight testing of
      spontaneous ocular torsion and of ocular counterrolling (OCR), reflexes governed
      by the gravity-responsive otolith organs in the inner ear. One astronaut, A, had
      a 30-day space mission on Euromir '94 and was examined monocularly with
      SensoMotoric Instruments video-oculography (VOG). The other two astronauts, B and
      C, were studied with a binocular VOG and flew an 180-day mission on Euromir '95.
      In space, spontaneous eye torsion in the upright position was found to be
      substantially offset from baseline Earth-based recordings in all three subjects
      for the duration of the flights. In addition, the binocular studies showed a
      marked torsional disconjugacy. On return to Earth, offset and torsional
      disconjugacy persisted for many days. OCR in response to 30 degrees right and
      left tilt was examined preflight and postflight. Compared to preflight, Astronaut
      A showed reduced OCR immediately postflight, which increased over the next few
      days. Both Astronauts B and C had increased OCR postflight, which gradually
      approached but did not achieve the preflight values over 13 days postflight. The
      adaptation of ocular torsion in space in one astronaut and not in the other two,
      and slow adaptation postflight, may reflect the lack of visual feed-back and the
      open loop nature of the otolith-ocular torsion reflex.

PMID- 9626650
TI  - Central and peripheral components of short latency vestibular responses in the
      chicken.
AB  - Far-field recordings of short latency vestibular responses to pulsed cranial
      translation are composed of a series of positive and negative peaks occurring
      within 10 ms following stimulus onset. In the bird, these vestibular evoked
      potentials (VsEPs) can be recorded noninvasively and have been shown in the
      chicken and quail to depend strictly upon the activation of the vestibular
      component of the eighth nerve. The utility of the VsEP in the study of vestibular
      systems is dependent upon a clear understanding of the neural sources of response
      components. The primary aim of the current research in the chicken was to
      critically test the hypotheses that 1) responses are generated by both peripheral
      and central neurons and 2) peaks P1 and N1 originate from first order vestibular
      neurons, whereas later waves primarily depend on activity in higher order
      neurons. The principal strategy used here was to surgically isolate the eighth
      nerve as it enters the brainstem. Interruption of primary afferents of the eighth
      nerve in the brainstem substantially reduced or eliminated peaks beyond P2,
      whereas P1 and N1 were generally spared. Surgical sections that spared vestibular
      pathways had little effect on responses. The degree of change in response
      components beyond N1 was correlated with the extent of damage to central
      vestibular relays. These findings support the conclusion that responses are
      produced by both peripheral and central elements of the vestibular system.
      Further, response peaks later than N1 appear to be dependent upon central relays,
      whereas P1 and N1 reflect activity of the peripheral nerve. These findings
      clarify the roles of peripheral and central neurons in the generation of
      vestibular evoked potentials and provide the basis for a more useful and detailed
      interpretation of data from vestibular response testing.

PMID- 9626651
TI  - The adequate stimulus for avian short latency vestibular responses to linear
      translation.
AB  - Transient linear acceleration stimuli have been shown to elicit eighth nerve
      vestibular compound action potentials in birds and mammals. The present study was
      undertaken to better define the nature of the adequate stimulus for neurons
      generating the response in the chicken (Gallus domesticus). In particular, the
      study evaluated the question of whether the neurons studied are most sensitive to
      the maximum level of linear acceleration achieved or to the rate of change in
      acceleration (da/dt, or jerk). To do this, vestibular response thresholds were
      measured as a function of stimulus onset slope. Traditional computer signal
      averaging was used to record responses to pulsed linear acceleration stimuli.
      Stimulus onset slope was systematically varied. Acceleration thresholds decreased
      with increasing stimulus onset slope (decreasing stimulus rise time). When
      stimuli were expressed in units of jerk (g/ms), thresholds were virtually
      constant for all stimulus rise times. Moreover, stimuli having identical jerk
      magnitudes but widely varying peak acceleration levels produced virtually
      identical responses. Vestibular response thresholds, latencies and amplitudes
      appear to be determined strictly by stimulus jerk magnitudes. Stimulus attributes
      such as peak acceleration or rise time alone do not provide sufficient
      information to predict response parameter quantities. Indeed, the major response
      parameters were shown to be virtually independent of peak acceleration levels or
      rise time when these stimulus features were isolated and considered separately.
      It is concluded that the neurons generating short latency vestibular evoked
      potentials do so as "jerk encoders" in the chicken. Primary afferents classified
      as "irregular", and which traditionally fall into the broad category of "dynamic"
      or "phasic" neurons, would seem to be the most likely candidates for the neural
      generators of short latency vestibular compound action potentials.

PMID- 9626652
TI  - Comparison of manual whole-body and passive and active head-on-body rotational
      testing with conventional rotary chair testing.
AB  - New methods of rotational testing of the vestibulo-ocular reflex (VOR) using
      manually generated or patient-generated sinusoidal head movements have recently
      been advocated for clinical use in circumstances where conventional rotary chair
      testing methods are not feasible. However, studies seeking to provide evidence
      for the validity of these methods by comparing their results with an accepted
      "gold-standard" have been conspicuously absent in the literature. In this study,
      we compared results for VOR gain, phase, and asymmetry obtained using whole-body
      and head-on-body rotational stimuli with those obtained by conventional rotary
      chair testing in 35 subjects with either unilateral or bilateral vestibular
      deficits over the range of frequencies from 0.025 Hz to 1 Hz. Our results provide
      evidence for the validity of manual whole-body and active and passive head-on
      body rotational testing methods by demonstrating excellent agreement between each
      of these and conventional rotational chair testing for VOR gain, phase, and
      asymmetry within the frequency range studied. Small differences at specific
      paradigm datapoints are likely secondary to subtle limitations of our
      experimental design. With further refinement, we expect the new methods will be
      useful adjuncts for evaluating patients with vestibular complaints in selected
      clinical situations.

PMID- 9626653
TI  - A homozygous mutation in the luteinizing hormone receptor causes partial Leydig
      cell hypoplasia: correlation between receptor activity and phenotype.
AB  - Leydig cell hypoplasia (LCH) is characterized by a decreased response of the
      Leydig cells to LH. As a result, patients with this syndrome display aberrant
      male development ranging from complete pseudohermaphroditism to males with
      micropenis but with otherwise normal sex characteristics. We have evaluated three
      brothers with a mild form of LCH. Analysis of their LH receptor (LHR) gene
      revealed a homozygous missense mutation resulting in a substitution of a lysine
      residue for a isoleucine residue at position 625 of the receptor. In vitro
      analysis of this mutant LHR, LHR(I625K), in HEK293 cells indicated that the
      signaling efficiency was significantly impaired, which explains the partial
      phenotype. We have compared this mutant LHR to two other mutant LHRs, LHR(A593P)
      and LHR(S616Y), identified in a complete and partial LCH patient, respectively.
      Although the ligand-binding affinity for all three mutant receptors was normal,
      the hormonal response of LHR(A593P) was completely absent and that of LHR(S616Y)
      and LHR(I625K) was severely impaired. Low cell surface expression explained the
      reduced response of LHR(S616Y), while for LHR(I625K) this diminished response was
      due to a combination of low cell surface expression and decreased coupling
      efficiency. For LHR(A593P), the absence of a reduced response resulted from both
      poor cell surface expression and a complete deficiency in coupling. Our
      experiments further show a clear correlation between the severity of the clinical
      phenotype of patients and overall receptor signal capacity, which is a
      combination of cell surface expression and coupling efficiency.

PMID- 9626654
TI  - Gonadotropins regulate inducible cyclic adenosine 3',5'-monophosphate early
      repressor in the rat ovary: implications for inhibin alpha subunit gene
      expression.
AB  - Many hormones that stimulate intracellular signaling pathways utilizing the
      second messenger cAMP affect gene expression in target cells through the
      activation of cAMP-responsive transcriptional regulatory proteins. Two of the
      best characterized of these are the cAMP-response element (CRE)-binding protein
      (CREB) and the CRE-modulatory protein (CREM). CREB and CREM are expressed as a
      family of proteins that have diverse activities in either stimulating or
      repressing gene transcription. In this study we examined the expression and
      regulation of the CREM gene in the rat ovary and in granulosa cells, to determine
      whether repressor isoforms of CREM might have a role in the LH-mediated
      suppression of inhibin alpha-subunit gene expression that occurs just before
      ovulation. We found that the predominant CREM mRNAs in the ovary correspond to
      previously described internal transcripts of the CREM gene that encode the
      inducible cAMP early repressor (ICER). ICER mRNAs are strongly induced in the
      ovary by exogenous gonadotropins in immature rats and are transiently expressed
      in the ovary immediately after the preovulatory LH surge in adult cycling rats.
      Although ICER is expressed in multiple ovarian cell types, expression in
      granulosa cells is observed only in response to LH stimulation. ICER mRNAs are
      also induced by the activation of cAMP-signaling pathways in cultured primary
      granulosa cells. To determine whether ICER can act as a functional repressor to
      modulate potential target genes such as the inhibin alpha-subunit gene, an ICER
      expression construct was transiently co-transfected into a granulosa cell line
      along with an inhibin alpha-subunit promoter-luciferase reporter gene. Both basal
      and cAMP-induced expression of the inhibin alpha-subunit promoter were suppressed
      by ICER. These studies reveal that CREM, a tissue-specific factor, is expressed
      and regulated by gonadotropins in the ovary, that the predominant CREM
      transcripts encode the repressor protein ICER, and that ICER is capable of
      inhibiting cAMP-induced expression of the inhibin alpha-subunit gene. Our
      findings are consistent with a role for repressors such as ICER in mediating the
      suppression of inhibin alpha-subunit gene expression that occurs in the ovary at
      the time of the preovulatory LH surge.

PMID- 9626655
TI  - Direct luteinizing hormone action triggers adrenocortical tumorigenesis in
      castrated mice transgenic for the murine inhibin alpha-subunit promoter/simian
      virus 40 T-antigen fusion gene.
AB  - Transgenic (TG) mice, expressing the Simian Virus 40 T-antigen (Tag) under a 6-kb
      fragment of the murine inhibin alpha-subunit promoter (inh alpha p), develop
      gonadal tumors of granulosa/theca or Leydig cell origin. We showed previously
      that adrenocortical tumors develop if the TG mice are gonadectomized but never
      develop in intact animals. However, if functional gonadectomy was induced by GnRH
      antagonist treatment or by cross-breeding the TG mice into the hypogonadotropic
      hpg genetic background, neither gonadal nor adrenal tumors appeared. Since the
      most obvious difference between the gonadectomized and GnRH-antagonist-treated or
      Tag/hpg double mutant mice is the elevated gonadotropin secretion in the first
      group, we examined whether the adrenal tumorigenesis would be gonadotropin
      dependent. Surprisingly, both the adrenal tumors and a cell line (C alpha 1)
      derived from one of them expressed highly functional LH receptors (LHR), as
      assessed by Northern hybridization, immunocytochemistry, ligand binding, and
      human CG (hCG)-stimulated cAMP and steroid production. No FSH receptor expression
      was found in the adrenal tumors by RT-PCR. hCG treatment of the C alpha 1 cells
      stimulated their proliferation, as measured by [3H]thymidine incorporation. This
      effect was related to hCG-stimulated steroidogenesis since progesterone,
      testosterone, and estradiol, at physiological concentrations, also stimulated the
      C alpha 1 cell proliferation. Different adrenocortical cells expressed initially
      LHR and Tag, whereas both were highly expressed in the tumor cells. In
      conclusion, the high level of functional LHR in the adrenal tumors indicates that
      this receptor can function as tumor promoter when ectopically expressed and
      stimulated by the ligand hormone.

PMID- 9626656
TI  - Residues Val254, His256, and Phe259 of the angiotensin II AT1 receptor are not
      involved in ligand binding but participate in signal transduction.
AB  - The role of the external third of helix VI of the angiotensin II (AII) AT1
      receptor for the interaction with its ligand and for the subsequent signal
      transduction was investigated by individually replacing residues 252-256 by Ala,
      and residues 259 or 261 by Tyr, and permanently transfecting the resulting
      mutants to Chinese hamster ovary (CHO) cells. Binding experiments showed no great
      changes in affinity of any of the mutants for AII, [Sar1]-AII, or [Sar1, Leu8]
      AII, but the affinity for the nonpeptide antagonist DuP753 was significantly
      decreased. The inositol phosphate response to AII was remarkably decreased in
      mutants V254A, H256A, and F259Y. These results indicate that AT1 residues Val254,
      His256, and Phe259 are not involved in ligand binding but participate in signal
      transduction. Based in these results and in others from the literature, it is
      suggested that, in addition to the His256 imidazole ring, the Phe259 aromatic
      ring interacts with the AII's Phe8, thus contributing to the signal-triggering
      mechanism.

PMID- 9626657
TI  - Stimulation of Jun N-terminal kinase (JNK) by gonadotropin-releasing hormone in
      pituitary alpha T3-1 cell line is mediated by protein kinase C, c-Src, and CDC42.
AB  - The signaling of ligands operating via heterotrimeric G proteins is mediated by a
      complex network that involves sequential phosphorylation events. Signaling by the
      G protein-coupled receptor GnRH was shown to include elevation of Ca2+ and
      activation of phospholipases, protein kinase C (PKC) and extra-cellular signal
      regulated kinase (ERK). In this study, GnRH was shown to activate Jun N-Terminal
      Kinase (JNK)/SAPK in alpha T3-1 cells in a PKC- and tyrosine kinase-dependent
      manner. GnRH as well as tumor-promoting agent (TPA) also increased c-Src
      activity, which peaked at 2 min after GnRH stimulation and was sensitive both to
      PKC and to tyrosine kinase inhibitors. Coexpression of Csk, which serves as a Src
      dominant interfering kinase, and constitutively active forms of Src, together
      with JNK, confirmed the involvement of c-Src downstream of PKC in the GnRH-JNK
      pathway. Coexpression of dominant negative and constitutively active forms of
      CDC42, Rac1, Ras, MEKK1, and MEK1 with JNK indicated that JNK activation by GnRH
      and TPA is mediated by CDC42 and MEKK1. Ras and MEK1, which are involved in a
      related mitogen-activated protein kinase (MAPK) pathway, did not affect JNK
      activation in alpha T3-1 cells. Taken together, our results suggest that GnRH
      stimulation of JNK activity is mediated by a unique pathway that includes
      sequential activation of PKC, c-Src, CDC42, and probably also MEKK1.

PMID- 9626658
TI  - p42/p44 mitogen-activated protein kinases activation is required for the insulin
      like growth factor-I/insulin induced proliferation, but inhibits differentiation,
      in rat fetal brown adipocytes.
AB  - Insulin-like growth factor I (IGF-I)/insulin induced cytosolic p42/p44 mitogen
      activated protein kinase (MAPK) activation in a time-dependent manner in fetal
      brown adipocytes, reaching a maximum at 5 min. Concurrently, nuclear p42/p44
      MAPKs were also activated by IGF-I and insulin. This cytosolic and nuclear MAPK
      activation was totally prevented by pretreatment with the MAPK kinase (MEK1)
      inhibitor, PD98059. These results indicate that MEK mediates the IGF-I/insulin
      induced p42/ p44 MAPK activation. IGF-I and insulin also increased the number of
      cells in the S + G2/M phases of the cell cycle, PCNA levels, and DNA synthesis at
      24 h. This IGF-I/insulin-induced proliferation was completely blunted by the
      presence of MEK1 inhibitor. In contrast, inhibition of MEK1 potentiated the IGF-I
      induced uncoupling protein (UCP-1) and the insulin-induced fatty acid synthase
      mRNAs expression after short and long-term treatments. Moreover, transient
      expression of a transfected active MEK construct (R4F) decreased IGF-I-induced
      UCP-1 and insulin-induced fatty acid synthase mRNA expression. These results
      demonstrate that p42/p44 MAPKs are essential intermediates for the IGF-I/insulin
      induced mitogenesis, but may have a negative role in the regulation of adipocytic
      and thermogenic differentiation in brown adipocytes.

PMID- 9626659
TI  - Divergent pathways regulate ligand-independent activation of ER alpha in SK-N-BE
      neuroblastoma and COS-1 renal carcinoma cells.
AB  - The alpha-estrogen receptor (ER alpha) transcriptional activity can be regulated
      either by binding to the cognate ligand or by intracellular signaling pathways
      responsive to a variety of factors acting through cell membrane receptors.
      Studies carried out in HeLa and COS-1 cells demonstrated that the cross-coupling
      between estrogen and growth factor receptors is mediated by p21ras and requires
      phosphorylation of a specific serine residue (Ser 118 in the human ER alpha and
      Ser 122 in mouse ER alpha) located in the ER alpha N-terminal activation function
      1 (AF-1). Likewise, in the SK-N-BE neuroblastoma cell line p21ras is involved in
      the cross-coupling between insulin and ER alpha receptors. However, in this cell
      line Ser 122 is not necessary for insulin-dependent activation of unliganded ER
      alpha. In addition, after insulin activation, the electrophoretic mobility
      associated to serine hyperphosphorylation of ER alpha in SK-N-BE and in COS-1
      cells is different. Our study rules out the possibility of tyrosine
      phosphorylation in unliganded ER alpha activation by means of transactivation
      studies of ER alpha tyrosine mutants and analysis of Tyr phosphorylation
      immunoreactivity. The two cofactors for steroid receptors RIP 140 and SRC-1 do
      not seem to be specifically involved in the insulin-induced ER alpha
      transactivation. The present study demonstrates the possibility of an
      alternative, cell-specific pathway of cross-coupling between intracellular and
      membrane receptors, which might be of importance for the understanding of the
      physiological significance of this mode of activation in the nervous system.

PMID- 9626660
TI  - Interaction and dissociation by ligands of estrogen receptor and Hsp90: the
      antiestrogen RU 58668 induces a protein synthesis-dependent clustering of the
      receptor in the cytoplasm.
AB  - The in vivo interaction of estrogen receptor (ER) and Hsp90, demonstrated in the
      absence of hormone by a nuclear cotranslocation assay of the cytoplasmic Hsp90
      with the karyophilic receptor, was disrupted by agonist and antagonist ligands,
      which, after dissociating the Hsp90, allowed the chaperone protein to be
      relocalized in the cytoplasm. The pure antiestrogen RU 58668 (RU), which was
      unable to stimulate an estrogen-dependent reporter gene and completely inhibited
      its estradiol-induced activity, also profoundly modified the subcellular
      distribution of ER in a specific time- and dose-dependent manner; ER appeared as
      speckled fluorescent clusters mainly located in the perinuclear region of the
      cytoplasm. The kinetics of appearance and reversal of the RU-dependent ER
      mislocalization in the presence or absence of cycloheximide demonstrated 1) that
      this effect was reversed by RU withdrawal or estradiol (E2) treatment, and 2)
      that cycloheximide with RU inhibited and reversed the ER cytoplasmic
      mislocalization induced by RU alone. These results point to a protein synthesis
      dependent step in the mechanism of action of this antiestrogen. After RU
      treatment, a large portion of ER was found in the particulate fraction of the
      cytoplasm. However, confocal and electron microscopic analysis showed that ER
      clusters were not associated with specific cytoplasmic organelles or
      compartments. Using ER mutants, it was found that the ligand binding domain was
      sufficient for RU to produce receptor mislocalization, while the constitutive
      nuclear localization signals were dispensable. We propose that the antiestrogenic
      properties of RU are primarily due to the induction of an aggregation-prone
      receptor conformation that cannot undertake the constitutive and the ligand
      induced nuclear localization function of the receptor because it is sequestered
      in the cytoplasm by fast turning over protein(s). We predict that antiestrogens
      able to block ER nuclear localization will behave as pure antihormones and will
      inhibit all the nuclear action of ER elicited by agonistic ligands or by ligand
      independent mechanisms such as growth factor stimulation.

PMID- 9626661
TI  - Folding requirements of the ligand-binding domain of the human mineralocorticoid
      receptor.
AB  - The effects of aldosterone are mediated by the mineralocorticoid receptor (MR), a
      ligand-dependent transcription factor. We investigated the structural
      determinants for ligand binding to the receptor using a series of human MR (hMR)
      deletion mutants. These proteins were produced in vitro in rabbit reticulocyte
      lysate and analyzed for their ability to bind agonists, antagonists, and the heat
      shock protein hsp90, which is a prerequisite for ligand binding to hMR. Studies
      on N terminus-truncated hMRs showed that the ligand-binding domain (LBD: amino
      acids 734-984) has a lower affinity for aldosterone than the entire receptor
      [dissociation constant (Kd) 2.9 vs. 0.47 nM] and does not interact with hsp90.
      Addition of the five-amino acid sequence (729-733) upstream from the LBD is
      necessary for interaction with hsp90, but a larger region is needed for high
      aldosterone affinity. Deletions at the C-terminal end of the hMR greatly reduced
      both agonist and antagonist binding: deletion of the last three amino acids
      reduced the affinity for aldosterone to 1/20 that of the entire protein, and
      deletion of the last four amino acids completely abolished binding, although the
      interaction with hsp90 was not affected. These effects can be explained by
      misfolding of the receptor, since limited proteolysis assays showed that
      deletions at the C-terminal end of hMR affect the accessibility of the cleavage
      sites within the DNA-binding domain and the N-terminal part of the hinge region
      to trypsin. Thus, our results support the idea that a short sequence upstream of
      the LBD is essential for the interaction of hMR with hsp90 and that the C
      terminus of hMR and hsp90 are both essential for folding of the receptor in a
      high-affinity hormone-binding state.

PMID- 9626662
TI  - A regulatory role for RIP140 in nuclear receptor activation.
AB  - Transcriptional regulation of gene expression by nuclear receptors requires
      negatively and positively acting cofactors. Recent models for receptor activation
      propose that certain receptors in the absence of ligands can recruit corepressors
      while ligand binding results in conformational changes leading to the recruitment
      of coactivators. Previous work has established a coactivator role for the SRC-1
      family members as well as an involvement of the coactivators CBP/p300 in nuclear
      receptor signaling. However, in addition to coactivators, ligand-activated
      nuclear receptors bind a number of different proteins that possibly serve other
      functions. Using peroxisome proliferator-activated receptor-alpha (PPAR alpha) as
      bait in a yeast two-hybrid screening, we have isolated nuclear factor RIP140
      whose function in receptor activation is unclear. We now report a detailed
      characterization of RIP140 action with a focus on the retinoid X receptor (RXR)
      heterodimeric receptors PPAR and thyroid hormone receptor (TR). We show that
      putative PPAR ligands enhance the interaction of RIP140 with the rat PPAR
      subtypes alpha and gamma in solution but not with PPAR/RXR heterodimers on DNA.
      However, RIP140 forms ternary complexes in the presence of RXR ligands. Similar
      experiments with TR support the high affinity of RIP140 to the RXR subunit and
      also suggest that either partner in the TR/RXR heterodimer can independently
      respond to ligand. Coactivation experiments in yeast and mammalian cells confirm
      the coactivator role for SRC-1, but not for RIP140. We provide important evidence
      that the in vitro binding of RIP140 and SRC-1 to nuclear receptors is
      competitive. Since RIP140 generally down-regulates receptor activity in mammalian
      cells and specifically down-regulates coactivation mediated by SRC-1, we propose
      a model in which RIP140 indirectly regulates nuclear receptor AF-2 activity by
      competition for coactivators such as SRC-1.

PMID- 9626663
TI  - Estrogen-induced retinoic acid receptor alpha 1 gene expression: role of estrogen
      receptor-Sp1 complex.
AB  - Retinoic acid receptor alpha 1 (RAR alpha 1) gene expression is induced by 17
      beta-estradiol (E2) in estrogen receptor (ER)-positive breast cancer cells, and
      the -100 to -49 region of the RAR alpha 1 gene promoter was previously shown to
      be required for E2-responsiveness. This region of the RAR alpha 1 promoter was
      further analyzed using the following oligonucleotides: -100 to -49 (RAR4); -79 to
      -56 (RAR3); -79 to -49 (RAR2); -100 to -58 (RAR1); and their derived promoter
      reporter constructs (pRAR4, pRAR3, pRAR2, and pRAR1). In transient transfection
      studies in MCF-7 human breast cancer cells, pRAR2 and pRAR1 were E2-responsive;
      both of the RAR alpha 1 gene promoter inserts contained two GC-rich sites and
      bound Sp1 protein in gel mobility shift assays. Using wild-type [32P]RAR2 and
      oligonucleotides mutated in one or both GC-rich sites, it was shown that ER
      enhanced Sp1 binding to both sites, but a ternary ER-Sp1-DNA complex was not
      observed in gel mobility shift assays. In transient transfection assays, each of
      the GC-rich motifs were sufficient for E2-induced transactivation. In ER-negative
      MDA-MB-231 cells transiently transfected with pRAR2, E2 responsiveness was
      observed only in cells cotransfected with wild-type ER or 11C-ER containing a
      deletion of the DNA-binding domain but not with ER variants that express
      activation function-1 (AF-1) or AF-2. Using a similar approach, it was shown that
      the GC-rich sites in RAR1 were also sufficient for ER activation. These results
      demonstrate that interaction of a transcriptionally active ER/Sp1 complex with GC
      rich motifs is required for hormone inducibility of the downstream region of the
      RAR alpha 1 gene promoter.

PMID- 9626664
TI  - Extreme position dependence of a canonical hormone response element.
AB  - Hormone response elements (HREs) are considered enhancers, activating
      transcription in a relatively position- and orientation-independent fashion. Upon
      binding to an HRE, steroid receptors presumably contact coactivators and/or
      proteins associated with the transcription initiation complex. As a receptor
      target site is moved further from a fixed position such as the TATA box, not only
      will the spatial separation of the receptor with respect to its interaction
      partners change, so will the orientation due to the rotation of the DNA helix.
      Additional constraints may be imposed by the assembly of DNA into chromatin.
      Therefore, we have endeavored to test rigorously the assertion that HRE action is
      position independent. We have constructed a series of 42 chloramphenicol
      acetyltransferase expression vectors that contain a single
      progesterone/glucocorticoid receptor-binding site separated from a TATA box by 4
      to 286 bp. The enhancer activity of the HRE was assessed after transient
      transfection of progesterone receptor-expressing fibroblasts. We find that the
      position of the HRE has a dramatic influence on induction by progestins. When
      closely juxtaposed to the TATA box, the HRE was unable to support a hormone
      response, perhaps due to direct steric hindrance with the transcription
      initiation complex. Full activity was gained by moving the HRE 10 bp further from
      the TATA sequence. As the HRE was moved incrementally further, activity remained
      near maximal over the next 26 bp. HRE activity then declined over the subsequent
      26 bp and remained low for another 2.5 helical turns. Surprisingly, a narrow
      window of HRE activity occurred at an HRE-TATA box separation of 90-100 bp.
      Little or no hormone-induced transcriptional activity was observed when the HRE
      was positioned further from the TATA box. The addition of a second HRE or a basal
      (nuclear factor-1) element failed to relieve this constraint. A similar series of
      experiments was carried out in a mammary carcinoma cell line that expressed high
      levels of both glucocorticoid and progestin receptors. Data in these cells
      indicate that glucocorticoids and progestins supported a similar HRE position
      activity profile, but this pattern of HRE activity was quite distinct from that
      seen in fibroblasts. This may be indicative of cell type-specific interactions
      between steroid receptors and adapter/coactivator proteins or cell type-specific
      activities such as acetylases or deacetylases participating in the steroid
      response.

PMID- 9626666
TI  - 14-3-3 proteins in neuronal development and function.
AB  - The 14-3-3 proteins are small, cytosolic, evolutionarily conserved proteins
      expressed abundantly in the nervous system. Although they were discovered more
      than 30 yr ago, their function in the nervous system has remained enigmatic.
      Several recent studies have helped to clarify their biological function.
      Crystallographic investigations have revealed that 14-3-3 proteins exist as
      dimers and that they contain a specific region for binding to other proteins. The
      interacting proteins, in turn, contain a 14-3-3 binding motif; proteins that
      interact with 14-3-3 dimers include PKC and Raf, protein kinases with critical
      roles in neuronal signaling. These proteins are capable of activating Raf in
      vitro, and this role has been verified by in vivo studies in Drosophila. Most
      interestingly, mutations in the Drosophila 14-3-3 genes disrupt neuronal
      differentiation, synaptic plasticity, and behavioral plasticity, establishing a
      role for these proteins in the development and function of the nervous system.

PMID- 9626668
TI  - Fingertip representation in the human somatosensory cortex: an fMRI study.
AB  - Eight right-handed adult humans underwent functional magnetic resonance imaging
      (fMRI) of their brain while a vibratory stimulus was applied to an individual
      digit tip (digit 1, 2, or 5) on the right hand. Multislice echoplanar imaging
      techniques were utilized during digit stimulation to investigate the organization
      of the human primary somatosensory (SI) cortex, cortical regions located on the
      upper bank of the Sylvian fissure (SII region), insula, and posterior parietal
      cortices. The t test and cluster size analyses were performed to produce cortical
      activation maps, which exhibited significant regions of interest (ROIs) in all
      four cortical regions investigated. The frequency of significant ROIs was much
      higher in SI and the SII region than in the insula and posterior parietal region.
      Multiple digit representations were observed in the primary somatosensory cortex,
      corresponding to the four anatomic subdivisions of this cortex (areas 3a, 3b, 1,
      and 2), suggesting that the organization of the human somatosensory cortex
      resembles that described in other primates. Overall, there was no simple medial
      to lateral somatotopic representation in individual subject activity maps.
      However, the spatial distance between digit 1 and digit 5 cortical
      representations was the greatest in both SI and the SII region within the group.
      Statistical analyses of multiple activity parameters showed significant
      differences between cortical regions and between digits, indicating that
      vibrotactile activations of the cortex are dependent on both the stimulated digit
      and cortical region investigated.

PMID- 9626669
TI  - Localization of language-related cortex with 15O-labeled water PET in patients
      with gliomas.
AB  - Measurement of relative cerebral blood flow (CBF) with 15O-labeled water PET has
      been widely used for brain mapping experiments on language functions in normal
      volunteers and patients with epilepsy. We focused on the question of whether PET
      during speech activation is an appropriate method for noninvasive determination
      of language-related cortex in patients with brain tumors. Furthermore, the
      suitability of the method for determination of hemispheric language dominance was
      examined and compared to the results of the Edinburgh Handedness Inventory. Ten
      right-handed and six left-handed patients with gliomas were examined prior to
      surgery while repeatedly performing word repetition and verb generation tasks. A
      set of volumes of interest (VOIs) was drawn on coregistered MRI in order to
      account for anatomic variability as well as anatomical alterations due to tumor
      mass effect. Repetition of nouns did not produce significant hemispheric
      differences. During stimulation by verb generation, reliable lateralized
      activations of Broca's area and supplementary motor area were detected in all
      right-handed patients. Of the left-handed patients, two showed clear right
      lateralization, two activated Broca's area bilaterally, and two had a pattern
      similar to that of right-handers. Patients with bilateral activations showed the
      strongest tendency toward bihandedness according to the handedness inventory.
      Lateralization of supplementary motor area in left-handers corresponded to
      lateralized activity in Broca's area. Tumors in the vicinity of language-related
      regions did not alter activation responses. In conclusion, measurement of CBF
      changes during verb generation permits identification of language-related areas
      in patients with gliomas with strong lateralization related to hemispheric
      dominance. These findings may be of particular clinical interest for left-handed
      patients.

PMID- 9626670
TI  - Uncoupling cognitive workload and prefrontal cortical physiology: a PET rCBF
      study.
AB  - Working memory is a fundamental cognitive building block involved in the short
      term maintenance and transformation of information. In neuropsychological
      studies, working memory has been shown to be of limited capacity; however, the
      neurophysiological concomitants of this capacity limitation have not been
      explored. In this study we used the [15O] water PET rCBF technique and
      statistical parametric mapping to examine normal subjects while they performed
      two cognitive tasks, both individually and simultaneously. One task was the
      Wisconsin Card Sorting Test, a complex reasoning task involving working memory,
      and the other was a rapidly paced auditory verbal shadowing task. When both tasks
      were performed simultaneously, there were significant decrements in performance
      compared with the individual task performance scores, indicating that cognitive
      workload had been increased. Analysis of the rCBF maps showed that when the two
      tasks were performed together, in contrast to when they were performed
      separately, there was less prefrontal activation. These results suggest that
      increases in cognitive workload do not necessarily recruit and then sustain
      cortical neurophysiological resources to a maximum, but rather may actually be
      accompanied by a diminution in cortical activity.

PMID- 9626671
TI  - Contribution of T2 relaxation time mapping in the evaluation of cryptogenic
      temporal lobe epilepsy.
AB  - In this study we compared the results of visual analysis of MR imaging with T2
      relaxation time mapping of the mesial structures in a group of 97 patients with
      cryptogenic temporal lobe epilepsy. All patients underwent a clinical
      neurological examination, neuropsychological investigation, prolonged video-EEG
      monitoring, SPECT imaging, MR imaging, and T2 relaxation time mapping. T2
      relaxation times were estimated with a Carr-Purcell-Meiboom-Gill pulse sequence
      with 48 echoes (15 to 720 ms). The mean T2 relaxation time value was 118.5 +/- 2
      ms in the hippocampi and 120.3 +/- 1.9 ms in the amygdala of 21 healthy subjects
      used as controls. T2 relaxation mapping revealed mesial temporal sclerosis in
      91.8% of the patients (often involving both the hippocampus and the amygdala) and
      evidenced bilateral involvement in 44.6% of the patients against 72.2 and 6.2%,
      respectively, for MR imaging. The ipsilateral and contralateral hippocampal T2
      relaxation time values did significantly correlate with seizure frequency and the
      contralateral hippocampal T2 relaxation time value with the duration of epilepsy.
      In conclusion, this quantitative method is highly sensitive for the detection of
      mesial temporal sclerosis and permits a better evaluation of the apparently
      normal contralateral mesial structures.

PMID- 9626665
TI  - Drugs of abuse and immediate-early genes in the forebrain.
AB  - A diverse array of chemical agents have been self administered by humans to alter
      the psychological state. Such drugs of abuse include both stimulants and
      depressants of the central nervous system. However, some commonalties must
      underlie the neurobiological actions of these drugs, since the desire to take the
      drugs often crosses from one drug to another. Studies have emphasized a role of
      the ventral striatum, especially the nucleus accumbens, in the actions of all
      drugs of abuse, although more recent studies have implicated larger regions of
      the forebrain. Induction of immediate-early genes has been studied extensively as
      a marker for activation of neurons in the central nervous system. In this review,
      we survey the literature reporting activation of immediate-early gene expression
      in the forebrain, in response to administration of drugs of abuse. All drugs of
      abuse activate immediate-early gene expression in the striatum, although each
      drug induces a particular neuroanatomical signature of activation. Most drugs of
      abuse activate immediate-early gene expression in several additional forebrain
      regions, including portions of the extended amygdala, cerebral cortex, lateral
      septum, and midline/intralaminar thalamic nuclei, although regional variations
      are found depending on the particular drug administered. Common
      neuropharmacological mechanisms responsible for activation of immediate-early
      gene expression in the forebrain involve dopaminergic and glutamatergic systems.
      Speculations on the biological significance and clinical relevance of immediate
      early gene expression in response to drugs of abuse are presented.

PMID- 9626672
TI  - Task-independent effect of time on rCBF.
AB  - Positron emission tomography was used to identify brain regions that showed
      general increase or decrease in regional cerebral blood flow (rCBF) across time
      that was task-independent. Twelve male subjects were scanned eight times: the
      first and last scans were taken while subjects performed a baseline fixation task
      and the middle six scans were taken while subjects performed a visuomotor
      activation task. To determine whether there was a consistency across different
      studies in the regions that showed this time-related change in rCBF two
      additional datasets were analyzed. There were similarities across all three
      studies in the regions that showed a monotonic task-independent change in
      activity. In all three studies there was a general bilateral decrease in rCBF of
      occipital and temporal areas across scans that might be related to habituation in
      the visual domain. Increases in rCBF were found in anterior cingulate,
      postcentral gyrus, and precentral gyrus across studies. It is likely that these
      changes reflect motor learning and motor program retrieval. This implies that,
      unless the experimenter controls for time-dependent changes in brain activity,
      the interpretation of task-related changes in rCBF may be confounded by these
      monotonic changes in rCBF. We present analytic strategies to identify
      experimental effects that are independent of nonspecific time effects, which can
      be used when it is not possible to control these effects through counterbalancing
      the experimental design. Nonspecific confounds are particularly relevant in
      functional MRI studies in which the number of scans acquired per study is much
      larger.

PMID- 9626667
TI  - Tyrosine hydroxylase and Parkinson's disease.
AB  - A consistent neurochemical abnormality in Parkinson's disease (PD) is
      degeneration of dopaminergic neurons in substantia nigra, leading to a reduction
      of striatal dopamine (DA) levels. As tyrosine hydroxylase (TH) catalyses the
      formation of L-DOPA, the rate-limiting step in the biosynthesis of DA, the
      disease can be considered as a TH-deficiency syndrome of the striatum. Similarly,
      some patients with hereditary L-DOPA-responsive dystonia, a neurological disorder
      with clinical similarities to PD, have mutations in the TH gene and decreased TH
      activity and/or stability. Thus, a logical and efficient treatment strategy for
      PD is based on correcting or bypassing the enzyme deficiency by treatment with L
      DOPA, DA agonists, inhibitors of DA metabolism, or brain grafts with cells
      expressing TH. A direct pathogenetic role of TH has also been suggested, as the
      enzyme is a source of reactive oxygen species (ROS) in vitro and a target for
      radical-mediated oxidative injury. Recently, it has been demonstrated that L-DOPA
      is effectively oxidized by mammalian TH in vitro, possibly contributing to the
      cytotoxic effects of DOPA. This enzyme may therefore be involved in the
      pathogenesis of PD at several different levels, in addition to being a promising
      candidate for developing new treatments of this disease.

PMID- 9626673
TI  - Wavelength-dependent differences between optically determined functional maps
      from macaque striate cortex.
AB  - This study investigates the role of wavelength in determining the source and
      dynamic range of activity-driven reflectance changes in macaque striate cortex.
      By using short (600 nm) and long (720 nm) wavelengths to map ocular dominance,
      orientation, and position from the same region of cortex on alternate trials, we
      isolated wavelength-dependent differences in the contributions of different
      tissue compartments. In agreement with previous reports, 600-nm illumination was
      found to produce optical signals that were more than twice the size of those
      obtained with 720-nm illumination. In addition, 600- and 720-nm images were found
      to correlate everywhere except in regions occluded by blood vessels, where the
      images obtained at 600 nm correlated with the overlying vasculature. Since the
      720-nm images do not correlate with the vasculature, this difference suggests
      that differential images obtained under 600-nm illumination are
      disproportionately sensitive to vascular events (e.g., changes in blood flow,
      volume, etc.). This finding is supported by the absorption spectra of hemoglobin
      and its derivatives, which absorb 600-nm light 4-1000 times more strongly than
      720-nm light. Hence, for the 40% of cortex covered by blood vessels larger than
      50 microns, images obtained at 600 nm are dominated by the vascular compartment
      to the exclusion of signals from the neural compartment below.

PMID- 9626674
TI  - Anatomical congruence of metabolic and electromagnetic activation signals during
      a self-paced motor task: a combined PET-MEG study.
AB  - We have investigated the degree of spatial correlation between the cerebral blood
      flow variations measured by positron emission tomography (PET) and the
      electromagnetic sources as measured by magnetoencephalography (MEG) in five
      subjects while performing a self-paced right index finger tapping task. Data were
      processed independently for each technique using both single-case and
      intersubject analysis. PET and MEG were coregistered with anatomical magnetic
      resonance images for each subject. Both extension and flexion motor-related
      fields were extracted from the MEG signal. Using the single dipole model we
      identified the motor evoked field 1 (MEF1) in all subjects and the motor field
      (MF) in three subjects. Individual and intersubject averaged PET data showed
      consistent contralateral primary sensorimotor (PSM) hand area and bilateral
      supplementary motor area activation. MEG individual and intersubject averaged
      results demonstrated that both MEF1 and MF dipoles were localized within the PSM
      PET activated area. Individual PSM mass center to dipole distance was 12 and 15.3
      mm on average for the MEF1 and the MF component, respectively. For the same
      components, the intersubject averaged analysis shows distances between the PET Z
      score maximum and the dipole locations of 6.3 and 15.0 mm, respectively. These
      results show that PET and MEG MEF1 activation signals spatially coincide within
      instrumental, registration, and modeling errors.

PMID- 9626675
TI  - Biophysical linkage between MRI and EEG amplitude in closed head injury.
AB  - Nuclear magnetic resonance of brain water proton (1H) T2 relaxation times and
      measures of absolute amplitude of EEG were obtained from 19 closed head injured
      patients. The relationship between EEG and T2 relaxation time differed as a
      function of both EEG frequency and gray matter versus white matter. White matter
      T2 relaxation time was positively correlated with increased EEG amplitude in the
      delta frequency band (0.5-3.5 Hz). In contrast, lengthened gray matter T2
      relaxation time was inversely correlated with EEG amplitude in the alpha and beta
      frequency bands (7-22 Hz). These findings are consistent with clinical EEG
      studies in which white matter lesions are related to increased EEG delta
      amplitude and gray matter lesions are related to decreased EEG alpha and beta
      frequency amplitude. Estimates of the severity of injury were obtained by
      neuropsychological measurements, in which lengthened T2 relaxation times in both
      the neocortical gray and white matter were correlated with diminished cognitive
      function. Decreased EEG beta and alpha amplitude and increased EEG delta
      amplitude were also correlated with diminished cognitive function. The findings
      imply a biophysical linkage between the state of protein-lipid structures of the
      brain as measured by the MRI and the scalp-recorded EEG.

PMID- 9626676
TI  - Dissociation of frontal and cerebellar activity in a cognitive task: evidence for
      a distinction between selection and search.
AB  - Human brain imaging studies have found that increases in functional activation in
      left-frontal cortex during cognitive tasks are often accompanied by similar
      increases in right-cerebellar regions. The present study used functional magnetic
      resonance imaging (fMRI) to investigate the distinctive contributions of these
      regions using a word stem completion task. Stems with many possible completions
      (MANY condition) were alternately presented with stems that had few possible
      completions (FEW condition), and subjects were asked to covertly complete each
      stem with a word and press a response switch for each successful completion.
      Prominent increases in activation in the MANY, relative to the FEW, condition
      were observed in the left middle frontal gyrus (Brodmann areas 9/10) and left
      caudate nucleus. In contrast, portions of the right-cerebellar hemisphere
      (posterior quadrangular lobule and superior semilunar lobule) and cerebellar
      vermis exhibited increases in the FEW, relative to the MANY, condition. This
      double dissociation suggests that the frontal and cerebellar regions make
      distinctive contributions to cognitive performance, with left-frontal (and
      striatal) activations reflecting response selection, which increases in
      difficulty when there are many appropriate responses, and right-cerebellar
      activation reflecting the search for responses, which increases in difficulty
      when even a single appropriate response is hard to retrieve.

PMID- 9626677
TI  - Somatosensory homunculus as drawn by MEG.
AB  - We studied a detailed somatosensory representation map of the human primary
      somatosensory cortex using magnetoencephalography. Somatosensory-evoked magnetic
      fields following tactile stimulation of multiple points in the right hemibody
      (including the tongue, lips, fingers, arm, trunk, leg, and foot) were analyzed in
      five normal subjects. We were able to estimate equivalent current dipoles (ECDs)
      following stimulation of the tongue, lips, fingers, palm, forearm, elbow, upper
      arm, and toes in most subjects and those following the stimulation of the chest,
      ankle, and thigh in one subject. The ECDs were located in the postcentral gyrus
      and generally arranged in order along the central sulcus, which is compatible
      with the somatosensory "homunculus." Linear distances, averaged in five subjects,
      from the receptive area of the thumb to that of the tongue, little finger,
      forearm, upper arm, and toes were estimated to be 2.42 +/- 0.28, 1.25 +/- 0.28,
      2.21 +/- 0.72, 2.75 +/- 0.63, and 5.29 +/- 0.48 cm, respectively. The moment of
      each ECD, which suggested the size of the cortical areas responsive to the
      stimulation, was also compatible with the bizarre proportion of the homunculus
      with a large tongue, lips, and fingers. According to these results, we were able
      to reproduce a large part of the somatosensory homunculus quantitatively on an
      individual brain MRI.

PMID- 9626678
TI  - Non-invasive microwave radiometry thermometry.
AB  - Near-field microwave radiometry and radiometric imaging are non-invasive
      techniques that are able to provide temperature information at a depth of up to
      several centimetres in subcutaneous tissues. They are based on the measurement of
      microwave electromagnetic thermal noise. This paper describes the basic
      principles, measurement methods and limitations of the techniques and the results
      of clinical studies, and it reviews recent progress.

PMID- 9626679
TI  - System response of the sinoatrial node during vagal stimulation.
AB  - The SA node response to modulations in canine vagal tone was investigated by
      means of the heart rate variability power spectrum. A new algorithm that was
      developed for accurate power spectrum estimation of short R-R segments is
      described. The performance of the algorithm was assessed for ECG recordings
      obtained from a controlled experiment, in which a frequency modulated pulse train
      was applied to the vagal nerve after vagal transaction and blockade of the
      sympathetic system. The power spectrum calculated for 20-25 heartbeats showed
      conspicuous spectral peaks in accordance with the different modulating
      frequencies between 0.1 and 0.3 Hz. The presence of spurious peaks was negligible
      even when the analysed signal segment consisted of only 20-25 beats. These
      results imply that for a certain range of modulating frequencies the sinoatrial
      node responds linearly to fluctuations in the parasympathetic tone. System
      identification methods that include fitting a linear model to the heart rate
      variability signal and analysis of the residuals were used for confirming the
      hypothesis of linearity. For higher frequencies of the modulating signal, usually
      above 0.3 Hz, the system was found to deviate from linearity.

PMID- 9626680
TI  - Repeatability of body sway measurements; day-to-day variation measured by sway
      magnetometry.
AB  - The postural stability of 30 normal subjects in the age range 15 to 64 years was
      measured on five separate occasions, using the sway magnetometry technique, to
      determine the day-to-day repeatability of this measurement technique. On each
      occasion the pathlength and area enclosed by movement of the hips in a horizontal
      plane were measured over two 30 s periods with eyes open and eyes closed, with
      subjects standing on a firm base. Day-to-day repeatability had a standard
      deviation of 14% for pathlength and 42% for area. Neither the age nor the sex of
      the subject had any demonstrable effect on the results.

PMID- 9626681
TI  - Quantifying changes in retinal circulation: the generation of parametric images
      from fluorescein angiograms.
AB  - Fluorescein angiography is an established technique for examining the functional
      integrity of the retinal circulation. The ability to quantify this function
      offers the possibility of early detection of changes due to retinopathy. We have
      developed a technique to generate functional, parametric images of the retinal
      circulation. A given angiogram is first registered to align consecutive frames.
      At each point in the retina, a graph of fluorescein intensity versus time is then
      constructed and fitted with a gamma variate curve. Parameters are extracted from
      these curves and formed into parametric images showing the variation in
      fluorescein passage across the entire area of the angiogram. Parameters examined
      to date include time to maximum intensity, time of arrival and rise time. The
      technique has been demonstrated using photographic and scanning laser
      ophthalmoscopic angiograms of both normal subjects and patients with a variety of
      retinopathies. The time to maximum images of the normal subjects reveals a
      similar fillings pattern in each case, whilst the pathologies present in the
      abnormal angiograms are clearly identified. The generation of functional time to
      maximum images enables the health of the retinal circulation to be quantified
      with respect to the rate at which the vasculature fills with fluorescein. This
      offers a potential tool for detecting the onset of retinopathy and monitoring its
      progression.

PMID- 9626682
TI  - Within- and between-day variability in transcutaneous Doppler ultrasound
      measurements of superior mesenteric artery blood flow (SMABF) in the fasted
      state.
AB  - This study assessed within- and between-day variability of human superior
      mesenteric artery blood flow (SMABF) using transcutaneous Doppler ultrasound. Two
      groups of healthy volunteers were studied after fasting overnight; six subjects
      were studied for one visit of 90 min duration (group 1) and six other subjects
      attended the laboratory for three separate visits of 30 min duration (group 2).
      Measurements of SMABF were made by a single, trained observer every 15 min, the
      angle of insonation of the Doppler beam being set both < 30 degrees and > 30
      degrees each time. Within a day (group 1), the angle of insonation had little
      effect upon SMABF measurements (values differed by less than 6%) and variability
      was low (mean coefficient of variation below 5%). SMABF measurements between days
      (group 2) were consistent (mean coefficient of variation ranging from 6 to 12%),
      but measurements made at angles of < 30 degrees had slightly lower standard error
      of the mean (SEM) and coefficient of variation (CV) than those above 30 degrees.
      Thus, in fasted subjects there is small within-visit or between-visit variability
      in SMABF assessed by a single trained observer using Doppler ultrasound. Slightly
      less variability is observed when scanning at angles of < 30 degrees, but this
      effect was not substantial and the correction factor for angle contained within
      the software of the ultrasound machine appeared to be reliable.

PMID- 9626683
TI  - A model for ultrasonic scattering in cancellous bone based on velocity
      fluctuations in a binary mixture.
AB  - A scattering model based on velocity fluctuations in a binary mixture (marrow fat
      and cortical matrix) was used to estimate the ultrasonic attenuation in
      cancellous bone as a function of volume fraction. The calculation of velocity
      fluctuations alone seems to be suitable for the qualitative estimation of
      attenuation. The predicted values of the attenuation were of the same order of
      magnitude as experimentally determined values from the literature. This agreement
      was achieved with only a small number of variables (the velocities of the two
      components and the scatterer size) in the model, representing a major advantage
      compared with other theories. Hence the suggested approach appears to be a good
      starting point for further theoretical investigations using scattering theories.
      However, this has to be accompanied by accurate ultrasonic and microstructural
      measurements.

PMID- 9626684
TI  - Diffraction and interface losses in broadband ultrasound attenuation measurements
      of the calcaneum.
AB  - Ultrasonic investigation of bone disease most frequently involves measurements on
      the heel, and the parameter most often used for this is the broadband ultrasound
      attenuation (BUA) which is the slope of the attenuation as a function of
      frequency between 0.2 and 0.6 MHz. In this study, the possible losses in the BUA
      measurement due to diffraction and interfaces have been discussed and evaluated
      using existing data and a standard diffraction model. The loss due to diffraction
      was found to depend critically upon whether a contact or immersion technique is
      used. For a contact method, we estimate that the diffraction loss can be greater
      than 10 dB MHz-1, whereas insertion devices typically will have losses of up to
      0.6 dB MHz-1, and it not always clear whether or how manufacturers have attempted
      to correct for this. Dispersion which is found in the os calcis has only a small
      effect on the diffraction loss, but it can cause a frequency dependent interface
      loss of about 0.2 dB MHz-1. It may be impossible to correct for these
      discrepancies in vivo as the necessary data for the individual components of the
      heel are not known. However the losses should be borne in mind as factors
      limiting the accuracy of the measurements and, in the case of in vitro
      investigations, may merit further study.

PMID- 9626685
TI  - A new method for automated blood pressure measurement.
AB  - We propose a new technique for automated indirect blood pressure measurement
      based on the auscultatory method. Systolic, diastolic and blood mean pressure are
      identified by looking at trend changes in the spectral energy dispersion of
      Korotkoff sounds. The detection is solely based on patient measurements, not on
      population studies. By comparing the automatic detection with common auditory
      detection, in 286 measurements taken in 15 subjects there was agreement (+/- 1
      sound--400 Pa error) in 278 cases for the systole and 276 cases for the diastole.

PMID- 9626686
TI  - Three methods compared for detecting the onset of alpha wave synchronization
      following eye closure.
AB  - Recent work indicates that the variation in the occipital alpha wave component of
      the EEG spectrum, controlled through eye closure, can be used by an untrained
      person to effect reliable activation of electrical devices. Here we describe and
      compare three real-time strategies, based on analogue and digital signal
      processing methods, of detecting the onset of alpha wave synchronization during
      eye closure. The goal of this work is to establish a method which satisfies the
      condition of rapid detection of alpha wave enhancement, thereby allowing for the
      efficient activation of devices, while simultaneously registering few or no false
      positives due to the natural variation in the alpha signal with eyes open. This
      work, based on measurements on 15 subjects in the age range 12 to 40 years,
      indicates that renal-time analysis of the EEG power spectrum provides for rapid
      detection of the onset of alpha wave synchronization while maintaining low counts
      of false positives.

PMID- 9626687
TI  - Electronic light microscopy combined with spectrophotometry allows real-time
      analysis of structures at the subcellular level.
AB  - A combination of microscopy (video-enhanced contrast microscopy) and
      spectrophotometry (which analyses online the spectra from the microscopic
      picture) is presented. This set-up allows the in vivo microscopic observation of
      cellular and subcellular structures as well as simultaneous online determination
      of cellular chromophores. To test our equipment we measured spectra of isolated
      red blood cells and NG 108-15 cells and correlated these spectra with the
      corresponding video-enhanced microscopic picture. By labelling specific cell
      organelles of astrocytes with in vivo fluorescent dyes, we visualized
      mitochondria and captured the corresponding spectra.

PMID- 9626688
TI  - Sources of error in bioimpedance spectroscopy.
AB  - Two different makes of bioimpedance spectrometer (UniQuest-SEAC SFB-3 and Xitron
      4000B) were used for a series of measurements on volunteers and patients in
      intensive care. Although each machine was accurate over the frequency range 5 to
      500 kHz when bench tested on model resistor-capacitor circuits, significant
      differences in their recorded impedance parameters appeared when used in vivo,
      especially on intensive care patients. A series of laboratory tests was performed
      on each machine simulating the situation in vivo to identify possible reasons for
      these differences. Whilst stray capacitance in the environment was identified as
      the major contributor to variability in high-frequency performance, interaction
      between electrode impedance and lead positioning was also a factor. The observed
      phase shift with frequency or time delay (Td) used in the Xitron modeling
      software appears to be the result of a time constant caused by stray capacitance
      and so is unlikely to have any biological meaning. Significant differences in the
      in vivo numerical values produced by bioimpedance spectrometers may be attributed
      to instrument design, data processing and, in particular, the clinical
      environment.

PMID- 9626689
TI  - A model of artefacts produced by stray capacitance during whole body or segmental
      bioimpedance spectroscopy.
AB  - We have developed a novel model for the simulation of artefacts which are
      produced by stray capacitance during bioimpedance spectroscopy. We focused on
      whole body and segmental measurements in the frequency range 5-1000 kHz. The
      current source was assumed to by asymmetric with respect to ground as is the case
      for many commercial devices. We considered the following stray pathways: 1, cable
      capacitance; 2, capacitance between neighbouring electrode leads; 3. capacitance
      between different body segments and earth; 4, capacitance between signal ground
      of the device and earth. According to our results the pathways 3 and 4 cause a
      significant spurious dispersion in the measured impedance spectra at frequencies
      > 500 kHz. During segmental measurements the spectra have been found to be
      sensitive to an interchange of the electrode cable pairs. The sensitivity was
      also observed in vivo and is due to asymmetry of the potential distribution along
      the segment with respect to earth. In contrast to previously published
      approaches, our model renders possible the simulation of this effect. However, it
      is unable to fully explain the deviations of in vivo measured impedance spectra
      from a single Cole circle. We postulate that the remaining deviations are due to
      a physiologically caused superposition of two dispersions from two different
      tissues.

PMID- 9626690
TI  - Pulmonary perfusion measured by means of electrical impedance tomography.
AB  - Electrical impedance tomography (EIT) is a recent imaging technique based on
      electrical impedance, offering the possibility of measuring pulmonary perfusion.
      In the present study the influence of several pulmonary haemodynamical parameters
      on the EIT signal were investigated. First, the influence on the systolic wave of
      the EIT signal (delta Zsys) of stroke volume, large pulmonary artery
      distensibility (both assessed by means of MRI) and the extent of the pulmonary
      peripheral vascular bed in 11 emphysematous patients (reduced peripheral vascular
      bed) and 9 controls (normal peripheral vascular bed) was investigated. Second,
      the influence of hypoxic pulmonary vasoconstriction on delta Zsys was examined in
      14 healthy subjects. Finally, the origin of the diastolic wave was examined in
      three patients with atrioventricular dissociation. Multiple regression analysis
      showed that delta Zsys was only dependent on the variable emphysema (p < 0.02),
      but not dependent on stroke volume (p < 0.3) or pulmonary artery distensibility
      (p > 0.9). The mean value of delta Zsys for emphysematous patients (131 +/- 32
      arbitrary units (AU)) was significantly lower (p < 0.001) than in the control
      group (200 +/- 39). In the group of healthy subjects delta Zsys decreased
      significantly (p < 0.001) during hypoxia (193 +/- 38 AU) compared with rest
      measurements (260 +/- 62 AU). The absence of the diastolic wave in the
      cardiological patients suggests the influence of reverse venous blood flow on the
      EIT signal. It is concluded that volume changes in the small pulmonary vessels
      contribute significantly to the EIT signal. Moreover, the hypoxia induced
      decrease in delta Zsys indicates the potential of EIT for measuring pulmonary
      vascular responses to external stimuli.

PMID- 9626691
TI  - Data analysis in multiple-frequency bioelectrical impedance analysis.
AB  - The performance of three analytical methods for multiple-frequency bioelectrical
      impedance analysis (MFBIA) data was assessed. The methods were the established
      method of Cole and Cole, the newly proposed method of Siconolfi and co-workers
      and a modification of this procedure. Method performance was assessed from the
      adequacy of the curve fitting techniques, as judged by the correlation
      coefficient and standard error of the estimate, and the accuracy of the different
      methods in determining the theoretical values of impedance parameters describing
      a set of model electrical circuits. The experimental data were well fitted by all
      curve-fitting procedures (r = 0.9 with SEE 0.3 to 3.5% or better for most circuit
      procedure combinations). Cole-Cole modelling provided the most accurate estimates
      of circuit impedance values, generally within 1-2% of the theoretical values,
      followed by the Siconolfi procedure using a sixth-order polynomial regression (1
      6% variation). None of the methods, however, accurately estimated circuit
      parameters when the measured impedances were low (< 20 omega) reflecting the
      electronic limits of the impedance meter used. These data suggest that Cole-Cole
      modelling remains the preferred method for the analysis of MFBIA data.

PMID- 9626692
TI  - Patient-instrument connection errors in bioelectrical impedance measurement.
AB  - Bioelectrical impedance in vivo measurement errors due to the connection between
      instrument and patient are analysed theoretically and experimentally. Special
      attention is paid to the patient cable capacitances and to the reduction of
      unwanted common-mode signals at the voltage amplifier input. Experiments with
      single-ended and symmetrical current sources, with different simulated body
      impedance values, with five types of cable connection and with three types of
      cable screen driving are carried out. The use of a balanced voltage-to-current
      transverter with a floating common point is recommended. Four separate patient
      cables should be used with separately driven screens by high-quality unity-gain
      buffers. Thus the impedance module measurement error can be reduced to below 1%
      in the range of 20 to 1000 omega and the phase measurement error to less than 0.3
      degree, for frequencies from 1 kHz to 300 kHz.

PMID- 9626693
TI  - Comparison of mean skin temperature using 'covered' versus 'uncovered' contact
      thermistors.
AB  - The purpose of this study was to compare the mean skin temperature (Tsk) obtained
      using 'covered' versus 'uncovered' contact thermistors in a variety of
      environmental conditions. Ten male subjects walked on a treadmill at 6.4 kph for
      30 min in three different environments: thermoneutral (23 degrees C/50% RH), hot
      humid (35 degrees C/80%), and hot-dry (42 degrees C/20%). Tsk was measured using
      three 'uncovered' contact thermistors, and three 'covered' thermistors. The
      'uncovered' probes were attached using acrylic rings that allowed the outer
      surface of the thermistors to have free exchange with the environment. The
      'covered' probes were affixed to the skin using foam patches and tape. The latter
      procedure is commonly used in many research and clinical laboratories. The
      'covered' probes resulted in a significantly (p < 0.05) higher Tsk under all
      three environmental conditions. The largest difference occurred in the
      thermoneutral condition with the 'covered' Tsk being 1.3 degrees C higher than
      the 'uncovered' Tsk. These results suggest that covering a contact skin
      thermistor hinders heat loss and results in an artificially high Tsk. It is hoped
      that the results of this study will encourage the adoption of 'uncovered' contact
      skin thermistors in the future.

PMID- 9626694
TI  - Theory of kinetic partitioning in protein folding with possible applications to
      prions.
AB  - This study focuses of the phenomenon of kinetic partitioning when a polypeptide
      chain has two ground-state conformations, one of which is kinetically more
      reachable than the other. We designed sequences for lattice model proteins with
      two different conformations of equal energy corresponding to the global energy
      minimum. Folding simulations revealed that one of these conformations was indeed
      much more kinetically accessible than the other. We found that the number and
      strength of local contacts in the ground-state conformation are the major factors
      that determine which conformation is reached faster; the greater the number of
      local contacts, the more kinetically reachable a conformation is. We present
      simple statistical-mechanical arguments to explain these findings. Our results
      may be relevant in explaining the phenomenology of such proteins as human
      plasminogen activator inhibitor-1 (PAI-1), photosystem II, and prions.

PMID- 9626696
TI  - The role played by environmental residues on sidechain torsional angles within
      homologous families of proteins: a new method of sidechain modeling.
AB  - We investigated the conservation of sidechain conformation for each residue
      within a homologous family of proteins in the Protein Data Bank (PDB) and
      performed sidechain modeling using this information. The information was
      represented by the probability of conserved sidechain torsional angles obtained
      from many families of proteins, and these were calculated for a pair of residues
      at topologically equivalent positions as a result of structural alignment.
      Probabilities were obtained for a pair of same amino acids and for a pair of
      different amino acids. The correlation between environmental residues and the
      fluctuation of probability was examined for the pair of same amino acid residues,
      and the simple probability was calculated for the pair of different amino acids.
      From the results on the same amino acid pairs, 17 amino acids, except for Ala,
      Gly, and Pro, were divided into two types: those that were influenced and those
      that were not influenced by the environmental residues. From results on different
      amino acid pairs, a replacement between large residues, such as Trp, Phe, and
      Tyr, was performed assuming conservation of their torsional angles within a
      homologous family of proteins. We performed sidechain modeling for 11 known
      proteins from their native and modeled backbones, respectively. With the native
      backbones, the percentage of the chi 1 angle correct within 30 degrees was found
      to be 67% and 80% for all and core residues, respectively. With the modeled
      backbones, the percentage of the correct chi 1 angle was found to be 60% and 72%
      for all and core residues, respectively. To estimate an upper limit on the
      accuracy for predicting sidechain conformations, we investigated the probability
      of conserved sidechain torsional angles for highly similar proteins having > 90%
      sequence identity and < 2.5-A X-ray resolution. In those proteins, 83% of the
      sidechain conformations were conserved for the chi 1 angle.

PMID- 9626695
TI  - Structural model of Dex protein from Penicillium minioluteum and its implications
      in the mechanism of catalysis.
AB  - The DEX gene encodes an extracellular dextranase (EC 3.2.1.11); this enzyme
      hydrolyzes the alpha(1,6) glucosidic bond contained in dextran to release small
      isomaltosaccharides. Sequence analysis has revealed only one homologous sequence,
      CB-8 protein, from Arthrobacter sp., with 30% sequence identity. The secondary
      structure prediction for Dex was corroborated by circular dichroism measurements.
      To explore the possibility that Dex protein might adopt a fold similar to any
      known structure, we conducted a threading search of a three-dimensional structure
      database. This search revealed that the Dex sequence is compatible with the
      galactose oxidase/methanol dehydrogenase/sialidase fold. A structural model of
      Dex based on these results is physically and biologically plausible and leads to
      testable predictions, including the prediction that Asp246 and Glu299 might be
      catalytic residues. Also, according to this model the Dex enzyme has a mechanism
      of hydrolysis with net inversion of anomeric configuration.

PMID- 9626697
TI  - Essential spaces defined by NMR structure ensembles and molecular dynamics
      simulation show significant overlap.
AB  - Large concerted motions of proteins which span its "essential space," are an
      important component of protein dynamics. We investigate to what extent structure
      ensembles generated with standard structure calculation techniques such as
      simulated annealing can capture these motions by comparing them to long-time
      molecular dynamics (MD) trajectories. The motions are analyzed by principal
      component analysis and compared using inner products of eigenvectors of the
      respective covariance matrices. Two very different systems are studied, the beta
      spectrin PH domain and the single-stranded DNA binding protein (ssDBP) from the
      filamentous phage Pf3. A comparison of the ensembles from NMR and MD shows
      significant overlap of the essential spaces, which in the case of ssDBP is
      extraordinarily high. The influence of variations in the specifications of
      distance restraints is investigated. We also study the influence of the selection
      criterion for the final structure ensemble on the definition of mobility. The
      results suggest a modified criterion that improves conformational sampling in
      terms of amplitudes of correlated motion.

PMID- 9626698
TI  - Direct observation of an altered quaternary-structure transition in a mutant
      aspartate transcarbamoylase.
AB  - Time-resolved small-angle X-ray scattering (TR-SAXS) was used to monitor the
      structural changes that occur upon the binding of the natural substrates to a
      mutant version of the allosteric enzyme aspartate transcarbamoylase from
      Escherichia coli, in which the creation of a critical link stabilizing the R
      state of the enzyme is hindered. Previously, SAXS experiments at equilibrium
      showed that the structures of the unligated mutant enzyme and the mutant enzyme
      saturated with a bisubstrate analog are indistinguishable from the T and R state
      structures, respectively, of the wild-type enzyme (Tauc et al., Protein Sci.
      3:1998-2004, 1994). However, as opposed to the wild-type enzyme, the combination
      of one substrate, carbamoyl phosphate, and succinate, an analog of aspartate, did
      not convert the mutant enzyme into the R state. By using TR-SAXS we have been
      able to study the transient steady-state during catalysis using the natural
      substrates rather than the nonreactive substrate analogs. The steady-state in the
      presence of saturating amount of substrates is a mixture of 60% T and 40% R
      structures, which is further converted entirely to R in the additional presence
      of ATP. These results provide a structural explanation for the reduced
      cooperativity observed with the mutant enzyme as well as for the stimulation by
      ATP at saturating concentrations of substrates. They also illustrate the crucial
      role played by domain motions and quaternary-structure changes for both the
      homotropic and heterotropic aspects of allostery.

PMID- 9626699
TI  - Structural investigation of C4b-binding protein by molecular modeling:
      localization of putative binding sites.
AB  - C4b-binding protein (C4BP) contributes to the regulation of the classical pathway
      of the complement system and plays an important role in blood coagulation. The
      main human C4BP isoform is composed of one beta-chain and seven alpha-chains
      essentially built from three and eight complement control protein (CCP) modules,
      respectively, followed by a nonrepeat carboxy-terminal region involved in
      polymerization of the chains. C4BP is known to interact with heparin, C4b,
      complement factor I, serum amyloid P component, streptococcal Arp and Sir
      proteins, and factor VIII/VIIIa via its alpha-chains and with protein S through
      its beta-chain. The principal aim of the present study was to localize regions of
      C4BP involved in the interaction with C4b, Arp, and heparin. For this purpose, a
      computer model of the 8 CCP modules of C4BP alpha-chain was constructed, taking
      into account data from previous electron microscopy (EM) studies. This structure
      was investigated in the context of known and/or new experimental data. Analysis
      of the alpha-chain model, together with monoclonal antibody studies and heparin
      binding experiments, suggests that a patch of positively charged residues, at the
      interface between the first and second CCP modules, plays an important role in
      the interaction between C4BP and C4b/Arp/Sir/heparin. Putative binding sites,
      secondary-structure prediction for the central core, and an overall reevaluation
      of the size of the C4BP molecule are also presented. An understanding of these
      intermolecular interactions should contribute to the rational design of potential
      therapeutic agents aiming at interfering specifically some of these protein
      protein interactions.

PMID- 9626700
TI  - Species dependence of enzyme-substrate encounter rates for triose phosphate
      isomerases.
AB  - Triose phosphate isomerase (TIM) is a diffusion-controlled enzyme whose rate is
      limited by the diffusional encounter of the negatively charged substrate
      glyceraldehyde 3-phosphate (GAP) with the homodimeric enzyme's active sites.
      Translational and orientational steering of GAP toward the active sites by the
      electrostatic field of chicken muscle TIM has been observed in previous Brownian
      dynamics (BD) simulations. Here we report simulations of the association of GAP
      with TIMs from four species with net charges at pH 7 varying from -12e to +12e.
      Computed second-order rate constants are in good agreement with experimental
      data. The BD simulations and computation of average Boltzmann factors of
      substrate-protein interaction energies show that the protein electrostatic
      potential enhances the rates for all the enzymes. There is much less variation in
      the computed rates than might be expected on the basis of the net charges.
      Comparison of the electrostatic potentials by means of similarity indices shows
      that this is due to conservation of the local electrostatic potentials around the
      active sites which are the primary determinants of electrostatic steering of the
      substrate.

PMID- 9626701
TI  - Interaction of human SRY protein with DNA: a molecular dynamics study.
AB  - Molecular dynamics simulations have been conducted to study the interaction of
      human sex-determining region Y (hSRY) protein with DNA. For this purpose,
      simulations of the hSRY high mobility group (HMG) domain (hSRY-HMG) with and
      without its DNA target site, a DNA octamer, and the DNA octamer alone have been
      carried out, employing the NMR solution structure of hSRY-HMG-DNA complex as a
      starting model. Analyses of the simulation results demonstrated that the
      interaction between hSRY and DNA was hydrophobic, just a few hydrogen bonds and
      only one water molecule as hydrogen-bonding bridge were observed at the protein
      DNA interface. These two hydrophobic cores in the hSRY-HMG domain were the
      physical basis of hSRY-HMG-DNA specific interaction. They not only maintained the
      stability of the complex, but also primarily caused the DNA deformation. The salt
      bridges formed between the positive-charged residues of hSRY and phosphate groups
      of DNA made the phosphate electroneutral, which was advantageous for the
      deformation of DNA and the formation of a stable complex. We predicted the
      structure of hSRY-HMG domain in the free state and found that both hSRY and DNA
      changed their conformations to achieve greater complementarity of geometries and
      properties during the binding process; that is, the protein increased the angle
      between its long and short arms to accommodate the DNA, and the DNA became bent
      severely to adapt to the protein, although the conformational change of DNA was
      more severe than that of the hSRY-HMG domain. The sequence specificity and the
      role of residue Met9 are also discussed.

PMID- 9626702
TI  - Functional conformational changes of endo-1,4-xylanase II from Trichoderma
      reesei: a molecular dynamics study.
AB  - Recent crystallographic studies have revealed a range of structural changes in
      the three-dimensional structure of endo-1,4-xylanase (XYNII) from Trichoderma
      reesei. The observed conformational changes can be described as snapshots of an
      open-close movement of the active site of XYNII. These structures were further
      analyzed in this study. In addition, a total of four 1 ns molecular dynamics (MD)
      simulations were performed representing different states of the enzyme. A
      comparison of the global and local changes found in the X-ray structures and the
      MD runs suggested that the simulations reproduced a similar kind of active site
      opening and closing as predicted by the crystal structures. The open-close
      movement was characterized by the use of distance difference matrixes and the
      Hinge-find program (Wriggers and Schulten, Proteins 29:1-14, 1997) to be a 'hinge
      bending' motion involving two large rigidly-moving regions and an extended hinge.
      This conformational feature is probably inherent to this molecular architecture
      and probably plays a role in the function of XYNII.

PMID- 9626703
TI  - Electrostatics, allostery, and activity of the yeast chorismate mutase.
AB  - The predicted active site of chorismate mutase of baker's yeast Saccharomyces
      cerevisiae has been studied by continuum electrostatics, molecular surface/volume
      calculations, and molecular modeling. Our study shows that despite being subject
      to an allosteric transition, the enzyme's active-site pocket neither decreased in
      volume nor deformed significantly in shape between the active R state and the
      inactive T state. We find that the polar atmosphere in the pocket is responsible
      for the enzyme's affinity. A single amino acid, Glu23, can adequately account for
      the atmospheric variation. This residue swings into the active-site pocket from
      the R state to the T state. In the R state, Glu23 on helix H2 doubly pairs with
      Arg204 and Lys208 of H11, which is packed against H2. In the T state, a slide
      occurs between H11 and H2 such that Glu23 can no longer interact with Lys208 and
      competes with Asp24 for interacting with Arg204. Consequently, Glu23 is found in
      the T state to couple with Arg157, an active-site residue critical to substrate
      binding. The tandem sliding of H11 in both monomers profoundly changes the
      interactions in the dimer interface. The loop between H11 and H12 demonstrates
      the largest conformational change. Hence, we establish a connection between the
      allosteric transition and the activity of the enzyme. The conformational change
      in the transition is suggested to propagate into the active-site pocket via a
      series of polar interactions that result in polarity reversal in the active-site
      pocket, which regulates the enzyme's activity.

PMID- 9626704
TI  - Density functional studies on herpes simplex virus type 1 thymidine kinase
      substrate interactions: the role of Tyr-172 and Met-128 in thymine fixation.
AB  - The enzyme herpes simplex virus type 1 thymidine kinase (HSV1 TK) salvages
      thymidine into the DNA metabolism of the virus. In the active site, the thymine
      ring of the nucleoside binds in a pocket, formed by two residues, Tyr-172 and Met
      128, in a sandwich-type orientation. To investigate the nature of the thymine
      enzyme pocket interactions, we have carried out density functional theory
      calculations with gradient-corrected exchange-correlation functionals of models
      of the thymine-HSV1 TK adduct. Our calculations indicate that the role of Met-128
      in the substrate fixation is purely steric and hydrophobic, while the substrate
      Tyr-172 interaction is essentially electrostatic in nature. These findings are
      completely consistent with the available catalytic properties of mutants on the
      128 position.

PMID- 9626705
TI  - Dissecting alpha-helices: position-specific analysis of alpha-helices in globular
      proteins.
AB  - An analysis of the amino acid distributions at 15 positions, viz., N", N', Ncap,
      N1, N2, N3, N4, Mid, C4, C3, C2, C1, Ccap, C', and C" in 1,131 alpha-helices
      reveals that each position has its own unique characteristics. In general,
      natural helix sequences optimize by identifying the residues to be avoided at a
      given position and minimizing the occurrence of these avoided residues rather
      than by maximizing the preferred residues at various positions. Ncap is most
      selective in its choice of residues, with six amino acids (S, D, T, N, G, and P)
      being preferred at this position and another 11 (V, I, F, A, K, L, Y, R, E, M,
      and Q) being strongly avoided. Ser, Asp, and Thr are all more preferred at Ncap
      position than Asn, whose role at helix N-terminus has been highlighted by earlier
      analyses. Furthermore, Asn is also found to be almost equally preferred at helix
      C-terminus and a novel structural motif is identified, involving a hydrogen bond
      formed by N delta 2 of Asn at Ccap or C1 position, with the backbone carbonyl
      oxygen four residues inside the helix. His also forms a similar motif at the C
      terminus. Pro is the most avoided residue in the main body (N4 to C4 positions)
      and at C-terminus, including Ccap of an alpha-helix. In 1,131 alpha-helices, no
      helix contains Pro at C3 or C2 positions. However, Pro is highly favoured at N1
      and C'. The doublet X-Pro, with Pro at C' position and extended backbone
      conformation for the X residue at Ccap, appears to be a common structural motif
      for termination of alpha-helices, in addition to the Schellman motif. Main body
      of the helix shows a high preference for aliphatic residues Ala, Leu, Val, and
      Ile, while these are avoided at helix termini. A propensity scale for amino acids
      to occur in the middle of helices has been obtained. Comparison of this scale
      with several previously reported scales shows that this scale correlates best
      with the experimentally determined values.

PMID- 9626706
TI  - Evidence of new cadmium binding sites in recombinant horse L-chain ferritin by
      anomalous Fourier difference map calculation.
AB  - We refined the structure of the tetragonal form of recombinant horse L-chain
      apoferritin to 2.0 A and we compared it with that of the cubic form previously
      refined to the same resolution. The major differences between the two structures
      concern the cadmium ions bound to the residues E130 at the threefold axes of the
      molecule. Taking advantage of the significant anomalous signal (f" = 3.6 e-) of
      cadmium at 1.375 A, the wavelength used here, we performed anomalous Fourier
      difference maps with the refined model phases. These maps reveal the positions of
      anomalous scatterers at different locations in the structure. Among these, some
      are found near residues that were known previously to bind metal ions, C48, E57,
      C126, D127, E130, and H132. But new cadmium binding sites are evidenced near
      residues E53, E56, E57, E60, and H114, which were suggested to be involved in the
      iron loading process. The quality of the anomalous Fourier difference map
      increases significantly with noncrystallographic symmetry map averaging. Such
      maps reveal density peaks that fit the positions of Met and Cys sulfur atoms,
      which are weak anomalous scatterers (f" = 0.44 e-).

PMID- 9626707
TI  - A conceptual framework for mental health services: the matrix model.
AB  - BACKGROUND: The reform of mental health services needs to be guided by an overall
      conceptual framework. Such a framework is important to avoid many risks,
      including extrapolating from a specific service site to other services, without
      taking into account local and regional variables. METHODS: A conceptual
      framework, the 'matrix model', is proposed. This model has been developed using
      the most relevant information that is necessary for describing and interpreting
      mental health services data as well as patient-based information. RESULTS: The
      'matrix model' has two dimensions: the geographical, which refers to three levels
      (country, local and patient) and the temporal, which refers to three phases
      (inputs, processes and outcomes). Using these two dimensions a nine-cell matrix
      is constructed to bring into focus critical issues for mental health services.
      The relevance of each level and each phase is briefly presented. CONCLUSIONS: The
      matrix is intended to assist clinicians, planners and researchers to deal with
      clinical phenomena, organizational issues, and research questions that share a
      degree of complexity that render inadequate analyses and the interventions made
      only at one level. The matrix model applies particularly to mental health systems
      of care that are provided with a public health framework, and is less useful for
      contexts that consist of clinicians offering only one-to-one treatments, within
      fragmented programmes of care.

PMID- 9626708
TI  - Disability and psychiatric disorders in an urban community: measurement,
      prevalence and outcomes.
AB  - BACKGROUND: The purpose of this analysis was to examine: (1) the prevalence of
      psychiatric disorders among disabled people, using seven different measures of
      disability; (2) variation in disability between and within psychiatric diagnostic
      categories; and (3) relationship of diagnosis and disability to health service
      utilization. METHOD: Data were drawn from Phase I and Phase II of the Eastern
      Baltimore Mental Health Survey, part of the Epidemiologic Catchment Area Program
      (ECA) conducted in 1980-1 to survey mental morbidity within the adult population.
      A total of 810 individuals received both a household interview and a standardized
      clinical psychiatric evaluation. Estimated prevalence rates were computed using
      appropriate survey sampling weights. RESULTS: Prevalence of disability ranged
      from 2.5 to 19.5%, varying with specific disability measure. Among those
      classified as disabled by any of the measures examined, 56 to 92% had a
      psychiatric disorder and serious chronic medical conditions were present in the
      majority of these cases (54 to 78%). Disability was expressed differently among
      the various diagnostic groups. Diagnostic category and disability were
      significant independent predictors of medical service utilization and receipt of
      disability payments. CONCLUSIONS: The majority of disabled adults living in the
      community have diagnosable psychiatric disorders, with the majority of these
      individuals suffering from significant chronic medical conditions as well, thus
      making co-morbidity the norm.

PMID- 9626709
TI  - Use of formal and informal sources of mental health care among older African
      American public-housing residents.
AB  - BACKGROUND: Elderly residents of public housing have high rates of psychiatric
      disorders, but most of those in need of care do not use any mental health
      service. This study examines the use of formal and alternative informal sources
      of mental health care in a sample of elderly African-American public-housing
      residents. METHOD: Data from an epidemiological survey of six Baltimore public
      housing developments for the elderly (weighted N = 818) were analysed to examine
      the utilization of mental health services by older African-American residents.
      Logistic regression analyses were used to determine correlates of using formal
      and informal sources by those needing mental health care. RESULTS: Thirty-five
      per cent of subjects needed mental health care. Less than half (47%) of those in
      need received any mental health care in the previous 6 months. Residents in need
      were more likely to use formal (38.5%) than informal sources (18.6%) for care.
      The strongest correlates of using formal providers were substance use disorder
      (OR = 15.62), Medicare insurance (OR = 10.31) and psychological distress (OR =
      10.27). The strongest correlates of using informal sources were perceiving little
      or no support from religious/spiritual beliefs (OR = 21.65), cognitive disorder
      (OR = 19.71) and having a confidant (OR = 15.07). CONCLUSIONS: Contrary to
      elderly African-Americans in general, those in public housing rely more on formal
      than informal sources for mental health problems. Nevertheless, both sources fail
      to fill the gap between need and met need. Interventions to increase
      identification, referral and treatment of elderly public-housing residents in
      need should target general medical providers and clergy and include assertive
      outreach by mental health specialists.

PMID- 9626710
TI  - Assessing relatives' needs for psychosocial interventions in schizophrenia: a
      relatives' version of the Cardinal Needs Schedule (RCNS).
AB  - BACKGROUND: The methodology for measuring the needs of patients with severe
      mental illness is now well established through the MRC Needs for Care Assessment
      Schedule and its modification in the form of the Cardinal Needs Assessment. This
      paper reports the rationale and construction of a relatives' version of the
      Cardinal Needs Schedule and looks at preliminary data reporting on reliability
      and validity. METHODS: Potential problem areas for relatives were identified from
      the literature. The criteria determining Cardinal Needs for each problem included
      objective threshold, carer concern, and carer cooperation. The reliability of the
      Schedule was assessed in a study whereby 27 relatives of patients with
      established schizophrenic illness completed two Schedules administered by two
      independent raters within a short time period. RESULTS: The Schedule was
      acceptably reliable for most areas of need although there were some difficulties
      associated with the cooperation criteria. Concurrent measures of relatives and
      patients including EE, relative distress and patient psychopathology indicated
      that the Relatives' Cardinal Needs Schedule shows acceptable validity when used
      with a sample of 45 relatives. CONCLUSIONS: The paper suggests that the Schedule
      may prove to be a useful tool for both clinicians and researchers interested in
      establishing and evaluating family interventions.

PMID- 9626711
TI  - A comparison of needs assessed by staff and by an epidemiologically
      representative sample of patients with psychosis.
AB  - BACKGROUND: Staff and severely mentally ill patients differ in their assessments
      of need. This study compares staff and patient assessments of need for people
      suffering from psychotic disorders. METHOD: The needs of an epidemiologically
      representative sample of 137 patients from a catchment area psychiatric service
      in South London who had an ICD-10 diagnosis of a functional psychotic disorder
      were assessed cross-sectionally by patients and staff, using the Camberwell
      Assessment of Need. RESULTS: Staff rated patients to have on average 6.1 needs,
      and patients rated 6.7 needs (t = 2.58, df = 136, P = 0.011). This difference was
      accounted for by the staff rating of 1.2 unmet needs and the patient rating of
      1.8 unmet needs (t = 3.58, df = 136, P < 0.001). There was no difference in
      rating of total number of met needs. There was no difference in ratings in
      relation to any patient sociodemographic characteristics. There was moderate or
      better agreement on the presence of a need for 13 of the 22 domains in the
      Camberwell Assessment of Need. CONCLUSIONS: Staff and patients moderately agree
      about met needs, but agree less often on unmet needs.

PMID- 9626712
TI  - Development of the World Health Organization WHOQOL-BREF quality of life
      assessment. The WHOQOL Group.
AB  - BACKGROUND: The paper reports on the development of the WHOQOL-BREF, an
      abbreyiated version of the WHOQOL-100 quality of life assessment. METHOD: The
      WHOQOL-BREF was derived from data collected using the WHOQOL-100. It produces
      scores for four domains related to quality of life: physical health,
      psychological, social relationships and environment. It also includes one facet
      on overall quality of life and general health. RESULTS: Domain scores produced by
      the WHOQOL-BREF correlate highly (0.89 or above) with WHOQOL-100 domain scores
      (calculated on a four domain structure). WHOQOL-BREF domain scores demonstrated
      good discriminant validity, content validity, internal consistency and test
      retest reliability. CONCLUSION: These data suggest that the WHOQOL-BREF provides
      a valid and reliable alternative to the assessment of domain profiles using the
      WHOQOL-100. It is envisaged that the WHOQOL-BREF will be most useful in studies
      that require a brief assessment of quality of life, for example, in large
      epidemiological studies and clinical trials where quality of life is of interest.
      In addition, the WHOQOL-BREF may be of use to health professionals in the
      assessment and evaluation of treatment efficacy.

PMID- 9626713
TI  - Abnormal neural response to feedback on planning and guessing tasks in patients
      with unipolar depression.
AB  - BACKGROUND: It has been suggested that patients with unipolar depression show
      abnormal responses to negative feedback in the performance of cognitive tasks.
      Positron emission tomography (PET) has previously identified blood flow
      abnormalities in depressed patients during cognitive performance. We have also
      used PET to identify regions where there is differential neural response to
      performance feedback in normal volunteers. In this study we aimed to test the
      hypothesis that blood flow in these regions, the medial caudate and ventromedial
      prefrontal cortex, would be abnormal in depressed patients. METHODS: Six patients
      with unipolar depression and six matched controls were scanned using PET while
      performing cognitive tasks in the presence and absence of feedback. RESULTS:
      Compared with controls, depressed patients failed to show significant activation
      in the medial caudate and ventromedial orbitofrontal cortex. Blood flow was lower
      and a differential response, observed in normals, under different task and
      feedback conditions was not seen in the patients. DISCUSSION: The findings
      suggest that the behavioural response to feedback in depressed patients is
      associated with an abnormal neural response within the medial caudate and
      ventromedial orbitofrontal cortex, regions implicated in reward mechanisms. We
      argue that the observed abnormalities may depend on a combination of
      psychological factors, with both cognitive and emotive components.

PMID- 9626714
TI  - Mood and neuropsychological function in depression: the role of corticosteroids
      and serotonin.
AB  - BACKGROUND: Depressed patients show deficits on neuropsychological tests.
      However, the basis of these impairments and their relationship with mood
      disturbance remains unclear. METHODS: This paper reviews the literature regarding
      the relationship between mood disturbance and neuropsychological impairment in
      depression and the evidence for serotonergic and hypothalamic-pituitary-adrenal
      (HPA) axis involvement in these two domains. RESULTS: Mood disturbance and
      neuropsychological impairment both occur in depression, but have no clear
      relationship in time or degree. Impairment of post-synaptic 5-HT1A receptor
      function may result in the symptom of low mood in depression. Depressed patients
      demonstrate abnormalities in the functional control of the HPA axis with a
      resultant hypercortisolaemia, which may impair neuropsychological function. These
      processes may be related given the extensive interactions between the
      serotonergic system and the HPA axis. CONCLUSIONS: We argue that there is a
      neurobiological cause of impaired neuropsychological function in depression. The
      complex relationship between neuropsychological function and mood may be a result
      of interactions between the serotonergic system and the HPA axis, particularly in
      the hippocampus with involvement of serotonergic 5-HT1A and glucocorticoid
      receptors. A primary dysfunction in these receptors will produce a lowering of
      mood and neuropsychological impairment respectively. Either dysfunction will
      result in a secondary impairment of the alternate system. Thus, the effective and
      psychological changes of depressive illness are likely to have complex
      relationships in time and severity to one another and the illness as a whole may
      result from a range of primary aetio-pathologies.

PMID- 9626715
TI  - The role of defeat and entrapment (arrested flight) in depression: an exploration
      of an evolutionary view.
AB  - BACKGROUND: The social rank theory of psychopathology suggests that with the
      evolution of social hierarchies various psychobiological mechanisms became
      attuned to the success or failure in conflict situations. Specifically,
      subordinates and those who have lost status are at greater risk of pathology than
      winners and those of higher status. In this theory concepts of defeat and
      entrapment are seen to be of special relevance to the study of depression. We
      outline the role of defeat and entrapment within the social rank theory of
      depression. METHODS: New self-report measures of entrapment and defeat were
      developed and used to test predictions of the social rank theory of depression.
      Both a sample of students and depressed patients were assessed with these new
      scales and other social rank measures (e.g. social comparison and submissive
      behaviour). RESULTS: The entrapment and defeat measures were found to have good
      psychometric properties and significantly correlated with depression. They were
      also strongly associated with other rank variables. Defeat maintained a strong
      association with depression even after controlling for hopelessness (r = 0.62),
      whereas the relationship between hopelessness and depression was substantially
      reduced when controlling for defeat. Entrapment and defeat added substantially to
      the explained variance of depression after controlling for the other social rank
      variables. CONCLUSIONS: Defeat and entrapment appear to be promising variables
      for the study of depression. These variables may also help to develop linkages
      between human and animal models of psychopathology.

PMID- 9626716
TI  - The epidemiology and classification of bulimia nervosa.
AB  - BACKGROUND: We sought to determine whether there was empirical support for the
      diagnostic thresholds of DSM-IV bulimia nervosa (BN) and whether an empirically
      derived typology resembled the diagnostic categories of DSM-IV. METHODS: Detailed
      information about bulimic behaviours were assessed via personal interview in a
      population-based sample of 1897 Caucasian female twins. We assessed the lifetime
      prevalence of the component bulimic behaviours and DSM-IV and DSM-III-R BN.
      Latent class analysis of nine separate bulimic symptoms was used to develop an
      empirical typology of bulimic behaviour. RESULTS: Although the lifetime
      prevalences of bingeing (23.6%) and vomiting (4.8%) were relatively common, DSM
      IV BN was distinctly uncommon (0.5%). The criterion that specified the frequency
      and duration of bingeing and vomiting was an important limiting condition.
      Analysis of alternative thresholds found little support for the DSM-IV thresholds
      requiring an average of twice per week for 3 months. Latent class analysis
      yielded an interpretable four class solution that had little overlap with the DSM
      IV typology. CONCLUSIONS: As in other studies of unselected samples of women, the
      lifetime presence of bulimic behaviours are relatively high. Our results suggest
      that the DSM-IV approach to categorizing bulimic behaviour inadequately captures
      the spectrum of lifetime bulimic behaviours in the general population.

PMID- 9626717
TI  - The role of exposure with response prevention in the cognitive-behavioural
      therapy for bulimia nervosa.
AB  - BACKGROUND: One hundred and thirty-five women with bulimia nervosa participated
      in a randomized clinical trial designed to determine whether the addition of
      exposure with response prevention to a core of cognitive-behavioural therapy
      (CBT) leads to greater clinical improvement and lower risk of relapse. We present
      results from the end of treatment and 6- and 12-month follow-up. METHODS:
      Participants received eight sessions of CBT and were then randomized to either
      exposure to pre-binge cues (B-ERP), exposure to pre-purge cues (P-ERP), or a
      relaxation training control condition (RELAX). RESULTS: CBT produced significant
      clinical change. At the end of the behavioural treatments, there were no
      significant differences across the three groups on abstinence (66% in B-ERP, 45%
      in P-ERP and 47% in RELAX), or frequency of bingeing and purging. B-ERP, but not
      P-ERP, significantly reduced anxiety on the cue reactivity assessment, food
      restriction, body dissatisfaction and depression. These differences were not
      maintained at 6-month follow-up. At 12-months, B-ERP was independently associated
      with lower food restriction and better global functioning. CONCLUSIONS: CBT is a
      highly effective treatment for bulimia nervosa. B-ERP was modestly superior to P
      ERP at post-treatment; however, the advantage did not remain throughout the
      follow-up interval. ERP for bulimia nervosa is an expensive and logistically
      complicated treatment that does not appear to offer any significant additive
      benefits that are proportional to the amount of effort required to implement the
      treatment.

PMID- 9626718
TI  - Twin studies of adult psychiatric and substance dependence disorders: are they
      biased by differences in the environmental experiences of monozygotic and
      dizygotic twins in childhood and adolescence?
AB  - BACKGROUND: Twin studies have long been used to disentangle the role of genetic
      and environmental factors in the aetiology of psychiatric disorders. However, the
      validity of the twin method depends on the equal environment assumption--that
      monozygotic (MZ) and dizygotic (DZ) twins are equally correlated in their
      exposure to environmental factors of aetiological importance for the disorder
      under study. METHODS: Both members of 822 female-female twin pairs from a
      population-based registry previously assessed for a range of psychiatric and
      substance use disorders were asked 12 questions assessing the similarity of their
      environmental experiences in childhood and adolescence. We examined whether the
      similarity of environmental experiences predicted concordance for psychiatric and
      substance abuse disorders by both a 'pair-wise' and 'individual' method utilizing
      logistic regression. We also examined smoking initiation, where prior evidence
      suggested a role for adolescent social environment. RESULTS: Three factors were
      derived from these items: 'Childhood treatment', 'Co-socialization' and
      'Similitude'. Members of twin pairs agreed substantially in their recollections
      of these experiences. Compared with DZ twins, MZ twins reported comparable
      resemblance in their childhood treatment, but socialized together more frequently
      and reported that parents, teachers and friends more commonly emphasized their
      similarities. None of these three factors significantly predicted twin
      resemblance for major depression, generalized anxiety disorder, panic disorder,
      phobias, nicotine dependence or alcohol dependence. However, co-socialization
      significantly predicted twin resemblance for smoking initiation and perhaps for
      bulimia. CONCLUSION: Differential environmental experiences of MZ and DZ twins in
      childhood and adolescence are unlikely to represent a substantial bias in twin
      studies of most major psychiatric and substance dependence disorders but may
      influence twin similarity for the initiation of substance use.

PMID- 9626719
TI  - A twin study of mortality after spousal bereavement.
AB  - BACKGROUND: Previous research has shown an increased risk of mortality after
      spousal bereavement, with the highest risk in the first weeks or months closest
      to the loss. One difficult issue in these designs is appropriate covariates and
      control groups. METHOD: This study is based on 1993 pairs of twins discordant for
      marital status and on 35860 married individuals from the Swedish Twin Registry
      born between 1886 and 1958 and followed for marital and vital status between 1981
      and 1993. RESULTS: Spousal bereavement was a risk factor for mortality for both
      men and women using the still married co-twin as a control to the widowed
      proband, and controlling for earlier health status and health-related risk
      factors. The mortality risk was higher for young-old (under 70 years)
      individuals, and for recently widowed than for longer-term widowed. Young-old
      women had a pattern with increased mortality risk during the first years after
      bereavement, but also a markedly decreased risk if they survived 4 years after
      bereavement, as compared to married women. CONCLUSIONS: The results support a
      causal effect of bereavement on mortality. The decrease in risk for long-term
      young-old women is congruent with reports by widows of psychological growth after
      bereavement, involving increased sense of mastery and competence after learning
      to live in new sets of circumstances following the loss of their husband.

PMID- 9626720
TI  - Obstetric complications, treatment response and brain morphology in adult-onset
      and early-onset males with schizophrenia.
AB  - BACKGROUND: Substantial variability in age at onset of illness and course of
      illness exists between patients with schizophrenia. Recent studies suggest that
      age at illness onset may be useful in defining biologically and clinically
      distinct subgroups of patients. METHODS: Two hundred and ten males with
      schizophrenia were classified as early-onset or adult-onset according to their
      age at first hospitalization. Birth history, clinical functioning and treatment
      response was assessed in a subgroup of patients. Brain anatomy was assessed from
      CT scans in all patients and in 32 non-psychiatric control subjects. RESULTS:
      Patients with an early-onset were likely to have a history of obstetric
      complications, a poor response to neuroleptic treatment, and showed no
      relationship between ventricle size and duration of illness. Adult-onset patients
      were less likely to have obstetric complications, more likely to respond to
      treatment in the first years of illness, and showed an association between brain
      structure and duration of illness. CONCLUSIONS: The distinction between early-
      and adult-onset patients may have important aetiological and treatment
      implications.

PMID- 9626721
TI  - Morphometry in schizophrenia revisited: height and its relationship to pre-morbid
      function.
AB  - BACKGROUND: Morphometry, the measurement of forms, is an ancient practice. In
      particular, schizophrenic somatology was popular early in this century, but has
      been essentially absent from the literature for over 30 years. More recently,
      evidence has grown to support the notion that aberrant neurodevelopment may play
      a role in the pathophysiology of schizophrenia. Is the body, like the brain,
      affected by abnormal development in these patients? METHODS: To evaluate global
      deficit in development and its relationship to pre-morbid function, height was
      compared in a large group (N = 226) of male schizophrenics and a group of healthy
      male controls (N = 142) equivalent in parental socio-economic status. Patients in
      the lower quartile of height were compared to those in the upper quartile of
      height. RESULTS: The patient group had a mean height of 177.1 cm, which was
      significantly shorter than the mean height of the control group of 179.4 (P <
      0.003). Those in the lower quartile had significantly poorer pre-morbid function
      as measured by: (1) psychosocial adjustment using the pre-morbid adjustment
      scales for childhood and adolescence/young adulthood, and (2) cognitive function
      using measures of school performance such as grades and need for special
      education. In addition, these measures of pre-morbid function correlated
      significantly with height when analysed using the entire sample. CONCLUSIONS:
      These findings provide further support to the idea that abnormal development may
      play a key role in the pathophysiology of schizophrenia. Furthermore, this is
      manifested as a global deficit in growth and function resulting in smaller
      stature, poorer social skills, and deficits in cognitive abilities.

PMID- 9626722
TI  - Capacity limitations in short-term memory in schizophrenia: tests of competing
      hypotheses.
AB  - BACKGROUND: Capacity limitation theories have proved to be surprisingly resilient
      in characterizing some of the cognitive deficits in schizophrenia. However, this
      perspective has not generally been applied to short-term verbal memory tasks. We
      explored this issue by first attempting to ascertain if gross misallocations of
      processing resources might explain impairments in short-term memory in
      schizophrenia on a classic digit span task and in a second study by attempting to
      determine what effects delay and memory set size had on a divided attention short
      term verbal memory paradigm. METHODS: In the first study 16 patients with
      schizophrenia and 21 normal controls received 40 trials of a three digit task and
      20 trials of a six digit span task. As the absolute number of digits presented
      and duration of presentation in two conditions were identical, subjects thus had
      equivalent 'opportunities' to make errors if distraction, in the sense of
      misallocation of cognitive resources, were at the root of poor performance. In
      the second study 15 patients with schizophrenia and 15 normal controls were
      tested in conditions in which two, four or six words were presented and in which
      rehearsal was prevented by an interference task (colour naming) for delays of 5,
      10 or 15 s. RESULTS: Patients had disproportionate difficulty on the six digit
      rather than the three digit condition, suggesting that deficits in the verbal
      working memory short-term store may not be the result of attentional factors. In
      the second study, patients' performance was differentially worsened by the
      interference task, by memory set size (i.e. a capacity limitation) and by delay,
      a measure of decay rate. CONCLUSIONS: In concert, these studies demonstrate that
      schizophrenia patients have difficulties on verbal short-term memory span tasks
      not because of misallocation of resources, but rather because of limitations in
      'representational capacity' and maintenance of information over delays.

PMID- 9626723
TI  - Self-monitoring dysfunction and the schizophrenic symptoms of alien control.
AB  - BACKGROUND: Frith & Done (1988) have proposed that the experience of alien
      control symptoms in schizophrenia is related to a failure by such individuals to
      monitor effectively their own willed intentions, actions and thoughts. METHOD: To
      examine this hypothesis, a heterogeneous group of 35 patients, all carrying a DSM
      III-R diagnosis of schizophrenia (or schizophreniform psychosis) and 24 non
      patient controls, completed a battery of neuropsychological and cognitive tests,
      which inter alia, included four putative measures of self-monitoring. Patients
      took part in a detailed clinical interview to assess current levels of
      symptomatology. RESULTS: Patients generally performed at a lower level on most
      components of the test battery, including the four self-monitoring tests.
      Moreover, patients currently experiencing symptoms of alien control tended to
      experience greater difficulty with each of the self-monitoring tests; an effect
      that was relatively independent of neuropsychological or general cognitive
      function. CONCLUSIONS: The relationship between poor self-monitoring and the
      presence of alien control symptoms provides support for Frith & Done's account of
      the origins of these symptoms in schizophrenia.

PMID- 9626724
TI  - Smooth pursuit and saccadic abnormalities in first-episode schizophrenia.
AB  - BACKGROUND: Previous studies of oculomotor dysfunction in schizophrenia have
      tended to concentrate on abnormalities of smooth pursuit eye tracking in chronic
      medicated patients. We report the results of a study of smooth pursuit, reflexive
      and antisaccade performance in drug naive and antipsychotic treated first-episode
      schizophrenic patients. METHODS: Smooth pursuit and saccadic eye movements were
      recorded in 36 first-episode schizophrenic patients and 36 controls matched for
      age and estimated IQ. The schizophrenic patients were divided into drug-naive (N
      = 17) and antipsychotic treated groups (N = 19). RESULTS: Smooth pursuit velocity
      gain was significantly lower than controls only in the drug-naive patients. The
      treated patients did not differ significantly from either the controls or the
      untreated group. In an antisaccade paradigm both treated and drug-naive
      schizophrenic patients demonstrated an increased number of errors, but only drug
      naive patients also demonstrated an increased latency in initiating correct
      antisaccades. CONCLUSIONS: These impairments are unlikely to be due to a
      generalized deficit in oculomotor function in the schizophrenic groups, as there
      were no differences between the groups in saccadic metrics on a reflexive saccade
      task. The results show that both smooth pursuit and saccadic abnormalities are
      present at the onset of schizophrenia and are integral to the disorder.

PMID- 9626726
TI  - Clinical factors associated with short-term changes in outcome of patients with
      somatized mental disorder in primary care.
AB  - BACKGROUND: There is little research that examines demographic, clinical and
      treatment factors associated with changes in physical symptoms, psychiatric
      symptoms and functional outcome in patients with somatized depression or anxiety
      in primary care. METHOD: Factors associated with the outcome of psychologized or
      somatized depression or anxiety were derived from the literature. These factors
      were tested individually for their effects on changes in physical symptoms,
      psychiatric symptoms and functional outcome between baseline consultation with
      the general practitioner and 1 or 3 months later in 215 patients with somatized
      depression or anxiety. Individual factors associated with a particular outcome,
      demographic, DSM-IV diagnosis and treatment variables were entered into a
      multiple regression analysis. RESULTS: Factors associated with a better outcome
      on all three types of outcome measure were the absence of generalized anxiety
      disorder and/or simple or social phobias, absence of physical pathology, and the
      prescription of fewer drugs, especially hypnotics or benzodiazepines. In
      addition, a better psychiatric symptom outcome was associated with the patients'
      perceived satisfaction with the general practitioner's understanding or
      explanation of the patient's problems. A better functional outcome was associated
      with having a job, less distress over physical symptoms, not receiving invalidity
      benefit and no referral to hospital. CONCLUSION: There are clinical and
      demographic factors associated with all types of short-term outcome in patients
      with somatized depression or anxiety but there are additional factors that are
      associated only with either psychiatric or functional outcome.

PMID- 9626725
TI  - Impact of improved depression treatment in primary care on daily functioning and
      disability.
AB  - BACKGROUND: Few data are available regarding the impact of improved depression
      treatment on daily functioning and disability. METHODS: In two studies of more
      intensive depression treatment in primary care, patients initiating
      antidepressant treatment were randomly assigned to either usual care or to a
      collaborative management programme including patient education, on-site mental
      health treatment, adjustment of antidepressant medication, behavioural activation
      and monitoring of medication adherence. Assessments at baseline as well as 4 and
      7 months included several measures of impairment, daily functioning and
      disability: self-rated overall health, number of bodily pains, number of
      somatization symptoms, changes in work due to health, reduction in leisure
      activities due to health, number of disability days and number of restricted
      activity days. RESULTS: Average data from the 4- and 7-month assessments in both
      studies, intervention patients reported fewer somatic symptoms (OR 0.68, 95% CI
      0.46, 0.99) and more favourable overall health (OR 0.50, 95% CI 0.28, 0.91).
      While intervention patients fared better on other measures of functional
      impairment and disability, none of these differences reached statistical
      significance. CONCLUSIONS: More effective acute-phase depression treatment
      reduced somatic distress and improved self-rated overall health. The absence of a
      significant intervention effect on other disability measures may reflect the
      brief treatment and follow-up period and the influence of other individual and
      environmental factors on disability.

PMID- 9626727
TI  - The effect of personality on withdrawal severity and taper outcome in
      benzodiazepine dependent patients.
AB  - BACKGROUND: Personality psychopathology exerts a significant and independent
      effect on the course of benzodiazepine (BZ) discontinuation, worsening the
      subjective severity of withdrawal symptoms and significantly increasing the
      occurrence of early taper failures. METHOD: One hundred and seventy-one patients
      participating in a BZ discontinuation programme were administered several
      personality measures prior to taper. Patients were stabilized for 3 weeks at
      their baseline BZ dosage and then tapered off 25% per week over 4 weeks, with the
      option to extend up to 6 weeks if necessary. RESULTS: High levels of passivity
      and dependency as assessed by the MMPI Dependence subcluster, and at a trend
      level high Eysenck Neuroticism and high TPQ Harm Avoidance contributed
      significantly to the prediction of benzodiazepine withdrawal severity. Though
      there was a high correlation between personality measures, psychopathology and
      adjusted BZ dose, the effects of personality on withdrawal severity was
      significant, particularly in the initial phases of BZ taper, when taper severity
      was still relatively mild. CONCLUSIONS: These findings indicate that clinical
      decisions on how to manage BZ tapering should be guided by personality
      assessments, in addition to the usual considerations of BZ dosage, residual
      psychopathology, duration of treatment, etc. The potential for difficulty with
      discontinuation related to personality traits should be one of the factors
      weighted in the risk-benefit assessment made in the planning of benzodiazepine
      treatment for patients with anxious symptomatology.

PMID- 9626728
TI  - Patient treatment insistence and medication craving in long-term low-dosage
      benzodiazepine prescriptions.
AB  - BACKGROUND: Long-term low-dosage dependence on benzodiazepines in traditionally
      explained by withdrawal symptoms. Previous research has not given much attention
      to reports that suggest that many patients oppose stopping benzodiazepines long
      before withdrawal symptoms have developed. This study investigates the scope of
      and factors associated with this pre-withdrawal treatment insistence. METHODS:
      Patients receiving long-term low-dosage benzodiazepines in primary care were
      asked to take a drug-holiday of at least 3 weeks. Sociodemographic, medication,
      morbidity and attitudinal variables were assessed in addition to the GPs'
      perceptions of their patients. RESULTS: Two-thirds of the patients rejected the
      drug-holiday proposal. Patients who refused a drug-holiday were less educated and
      were using a higher percentage of long-acting benzodiazepines than patients who
      accepted the drug-holiday proposal. Those who refused were seen by their GPs as
      being more complaining, harder to satisfy and less co-operative. CONCLUSIONS:
      These results provide evidence for drug-seeking or craving behaviour of patients
      who receive low-dosage benzodiazepine prescriptions. A major problem in
      benzodiazepine withdrawal occurs before the withdrawal programme has even begun.
      These data show that benzodiazepine low-dosage dependence should be considered a
      real form of dependence.

PMID- 9626729
TI  - Three- to 5-year prospective follow-up of outcome in major depression.
AB  - BACKGROUND: A Dutch cohort of predominantly out-patient DSM-III-R major
      depressive patients was followed for 3 to 5 years after start of treatment in a
      psycho-neuro-endocrinological prediction study. The study design permitted
      description of the course of remissions, relapses and recurrences. METHODS:
      Pharmacological treatment was standardized, psychotherapy was tailored to the
      needs of the patient, follow-ups were done monthly until 3 years or more after
      the initial recruitment. RESULTS: After 9 months 49% of the patients had reached
      full remission and 45% were in partial remission. During the following 3 to 5
      years 82% of the patients had reached a period of full remission. Sixteen per
      cent of the patients needed 2 years or more before full remission. A relapse or
      recurrence rate of 41% within 5 years was found. Patients with residual symptoms
      relapsed particularly in the first 4 months after remission, while patients
      without residual symptoms recurred mainly after 12 months after remission.
      Previous depressive episodes and psychoticism predicted relapse. Psychomotor
      retardation at inception predicted a longer time to partial remission.
      CONCLUSION: In most cases, major depression is a seriously impairing episodic
      disease. This is also true for a sample of predominantly out-patients treated at
      a university clinic.

PMID- 9626731
TI  - [Synchronization between preverbal vocalizations and motor actions in early
      infancy. I: Pre-canonical babbling vocalizations synchronize with rhythmic body
      movements before the onset of canonical babbling].
AB  - This study reports the synchronization between vocal behaviors and motor actions
      in infants at the prelinguistic stage. Four Japanese infants were studied from
      the age of 4-6 months to 11 months. For all infants, a 40-min segment was
      selected from the 60-90 min observation recording taken on each month. All the
      vocalizations and motor actions recorded in the segment were transcribed. The
      results show that a behavioral synchronization occurred between vocalizations and
      rhythmic actions in infants at the prelinguistic stage. The synchronization was
      particularly obvious in the month immediately before the onset of canonical
      babbling. These findings suggest that the synchronization between vocalizations
      and rhythmic actions may have the function of promoting infants to produce
      canonical babbling, that is indispensable for the acquisition of spoken language.

PMID- 9626730
TI  - Dysfunctional parenting as a risk factor to lifetime depression in a sample of
      employed Japanese adults: evidence for the 'affectionless control' hypothesis.
AB  - BACKGROUND: Although many case-control studies have replicated an association
      between dysfunctional parenting and a lifetime diagnosis of depression, few
      epidemiological studies have explored the association. In addition, little is
      known about the association in non-western countries. METHODS: Using logistic
      regression analyses, additive and interactive contributions of parental child
      rearing behaviours, as measured by the Parental Bonding Instrument (PBI), toward
      the risk for having a lifetime diagnosis of major depressive disorder were
      explored in 418 employed Japanese adults. The diagnosis was provided by using the
      Inventory to Diagnose Depression, lifetime version. The analyses were conducted
      for male and female subjects separately. RESULTS: Parental care rather than
      parental protection was primary in predicting lifetime depression in both male
      and female subjects. An interactive combination of low care and high protection
      ('affectionless control') was a significant risk factor for lifetime depression
      in male respondents' reporting child-rearing behaviours of both parents and
      female respondents' reporting paternal child-rearing behaviours. Model
      improvements when entering the PBI scores were larger in male subjects than in
      female subjects. CONCLUSIONS: The results suggested that a combination of low
      care and over-protection increases a risk to lifetime depression even in a non
      clinical sample; that an association between dysfunctional parenting
      (particularly low care) and the development of depression is independent of
      culture; and that Japanese boys are more sensitive than Japanese girls to
      dysfunctional parenting as regards the development of depression.

PMID- 9626732
TI  - [Construction of a scale for college life anxiety and its reliability and
      validity].
AB  - The purpose of this study are to construct the College Life Anxiety Scale for
      measuring the level of college students' anxiety and to examine its reliability
      and validity. After collecting items about the anxiety in college life, factor
      analysis was performed on the data obtained from 2,782 college students. The
      result, firstly, showed that the College Life Anxiety Scale consisting of 30
      items had three factors, which were daily life anxiety, test anxiety and college
      maladjustment. Secondly, it was indicated that the Scale had both high test
      retest reliability and internal consistency (.82 and .84, respectively). It was
      also suggested that the Scale had high content, clinical, and criterion-related
      validities. In conclusion, the College Life Anxiety Scale is well able to measure
      the level of college students' anxiety in their usual life.

PMID- 9626733
TI  - [Temporal illusory conjunction in RSVP tasks: effects of target complexity].
AB  - We examined the complexity effects of stimuli and tasks on temporal illusory
      conjunction in the Rapid Serial Visual Presentation (RSVP) tasks. Subjects were
      asked to report the partially defined target. We found that error patterns
      greatly depended on the visual complexity of stimuli. In the case of visually
      complex stimuli such as Kanji characters consisting of many strokes, pre-target
      intrusion errors were dominant. In contrast, post-target intrusion errors mainly
      occurred for visually simple stimuli such as alphabetic letters. Moreover, when
      target letters were not defined by a specific feature, pre-target intrusion
      errors were dominant for alphabetic letters. These results were discussed in view
      of the limited capacity of visual attention.

PMID- 9626734
TI  - [Effects of negative-sentence suggestions under light hypnotic states on feelings
      and behaviors].
AB  - The purpose of this study was to examine the effects of negative-sentence
      suggestions on feelings and behaviors. Feelings and behaviors were classified
      under the axes of pleasant-unpleasant, and low-high activity. Sixteen subjects
      (six males and ten females) were induced into a light hypnotic state, and were
      given suggestions of feelings and behaviors in negative-sentence form. Aside of
      the above-mentioned suggestions, suggestions of neutral feeling and behavior in
      affirmative-sentence form was given as baseline. The subjects were then requested
      to rate the effect, which was stated in affirmative-sentence form. For example,
      if subject was given a negative-sentence suggestion that your feelings are not
      sad, then subject asked to rate his feelings of sadness. The results showed that
      negative-sentence suggestions had affirmative effects when the rated feeling was
      unpleasant, regardless of its activity level. They had negative effects when the
      rated feeling or behavior was pleasant and low in activity.

PMID- 9626735
TI  - [The effect of accuracy motivation on face function in person perception].
AB  - The present study investigated the effects of accuracy motivation and face
      attractiveness on person perception. Sixty-two female undergraduate and
      professional school students participated in an experiment. Half of them were
      motivated to form accurate impression by experimental manipulations of
      accountability (expecting to describe their impression later to a third party).
      After studying behavioral descriptions and photograph of target, they were asked
      to form impression and recall the descriptions. Main results were as follows: (1)
      On social desirability, accuracy motivation reduced the effect of positive face.
      (2) Accuracy motivation induced subjects to recall more behavioral descriptions.

PMID- 9626736
TI  - [Verbal short-term memory deficit in Alzheimer's disease: an examination with the
      free recall paradigm].
AB  - To examine the relationship between short-term memory deficit and severity of the
      dementia in Alzheimer's disease, free recall of word lists was investigated.
      Twenty-seven patients with diagnosis of probable Alzheimer's disease according to
      NINCDS ADRDA criteria, and twelve age-matched controls participated in the study.
      Patients were divided into two subgroups: fourteen mild and thirteen moderate
      dementia by Clinical Dementia Rating (CDR). To evaluate short-term and long-term
      memory components separately, two measures were used: recency effect in the
      serial-position free-recall curve, and intra-trial retention interval developed
      by Tulving and Colotla (1970). Mildly demented patients showed a long-term memory
      deficit with almost normal short-term memory, but moderate ones showed an overall
      reduction in both measures. These results suggest that memory disorder in
      Alzheimer's disease changes not only quantitatively but also qualitatively with
      the progress of dementia, and short-term memory is relatively preserved in the
      early stage of the disease.

PMID- 9626737
TI  - [A study on the individual differences of the experience of hypnagogic imagery].
AB  - Having defined the distinction between hypnagogic imagery and dreams, a
      preliminary study on the individual differences in the experience of visual
      hypnagogic imagery was conducted. (1) A questionnaire on visual hypnagogic
      experience was administered to 796 students. The results suggested that previous
      researches on the incidence of this experience might have suffered from ambiguous
      definitions. (2) The Scale of Mental Imagery (Hasegawa, 1992) was administered to
      330 of the same students, Eysenck Personality Questionnaire to 305 students, and
      S-A Creativity Test (Sozosei-shinri-kenkyukai, 1969) to 221 students. The
      frequency of hypnagogic experiences was significantly associated with the scores
      of "the vividness of mental imagery", "neuroticism", and "creativity". (3) Based
      on these results, a proposed research problem on hypnagogic imagery was
      discussed.

PMID- 9626738
TI  - [The multidimensional property of the self and self-reference effect].
AB  - It has been proposed that self-referent memory of verbal materials requires
      multidimensional processing that corresponds to the person's cognitive structure
      of the self (Horiuchi, 1996). In this study, two experiments were conducted to
      investigate the hypothesis that self-reference effect was due to information
      processing that was deeper and broader in self-referent than in semantic or other
      referent memory. In Experiment 1, recall under self-reference condition was
      better than semantic condition. However, six-dimension processing condition, with
      extroversion, emotional stability, etc., was not significantly better than the
      self-reference condition. In Experiment 2, with mother as the other, other
      referent memory was as good as that under three-dimension processing condition,
      using such dimensions of others as social desirability. However, recall under
      these conditions was inferior to that under self-reference condition. These
      results suggest that the self-reference effect is due to the multidimensional
      property of self cognition.

PMID- 9626739
TI  - [The history and current state of communication avoidance research].
AB  - The ability to communicate effectively has a profound impact on academic ability
      and social status in the United States. As such, communication avoidance may
      impart critical consequences on individuals who suffer from it. Within the
      communication discipline, communication avoidance is an extensive body of
      research with a relatively long history. Central to communication avoidance
      research is the concept of communication apprehension (CA). However, in
      comparison with research conducted in the United States, CA research in Japan
      remains in its genesis. This review thus focuses on communication apprehension
      and related constructs. Starting with an explanation of the magnitude of the
      problem of communication avoidance, a definition of CA is presented, and an
      overview of the related constructs of reticence, shyness, and other communication
      related fears is introduced. Basic CA treatment programs and personality
      correlates of CA are also covered. The review closes by offering suggestions for
      future CA research in Japan.

PMID- 9626740
TI  - [History of the Turkish angora goat with remarks on the wild ancestor of the
      domestic coat].
AB  - The study describes the ancient (3000 B.C.-15th/16th Century A.D.) and the more
      recent (16th-20th Century A.D.) history of the Turkish Angora goat as based on a
      broad and intensive evaluation of relevant literature. Moreover, important
      structural features of the typical biotope of this caprine breed are explained,
      essential basic information from a comparative zoological point of view is added
      with regard to the development of goat domestication, and specific details
      relating to the history of civilization are supplied. For a better understanding
      of all the different topics dealt with, selected and mostly original
      illustrations are included.

PMID- 9626741
TI  - [Case report. Three ostriches (Struthio camelus L., 1758), female, 18, 20 and 24
      months old].

PMID- 9626743
TI  - [Greenish discolorations of beef musculature and their assessment according the
      meat hygiene regulations. A case report].
AB  - In muscular tissue samples from two cows of different origin numerous greenish,
      spotlike tissue discolourations were diagnosed as eosinophilic myositis.
      Sarcosporidiosis is being suspected as the most likely cause. Factors leading to
      such cases of myositis due to sarcosporidiosis which is wide-spread in cattle and
      normally inapparent are largely unknown. According to Swiss and German meat
      inspection directives beef carcasses with these discolourations have to be
      declared as unfit for human consumption. However, during meat inspection such
      cases of myositis are problematic to diagnose, because the lesions are only
      visible on the cut end of muscle tissue. Hence, they can pass unnoticed through
      carcass inspection.

PMID- 9626742
TI  - [Utility of a CO2 micro-system for diagnosis of acid-base equilibrium disorders
      in cows with abomasal displacement].
AB  - The so-called Harleco apparatus, a micro-system for determination of total CO2,
      was tested on samples from 200 cows with abomasal displacements. Plasma
      bicarbonate concentration (pbc) determined with blood gas analysors were used as
      the reference method. RESULTS: (1) The pbc of 38.0% of the cows was considered
      normal (22-28 mmol/l), 51.5% of the cows had metabolic alkalosis (pbc > 20
      mmol/l), while 10.5% were acidotic (pbc < 22 mmol/l). (2) Values for pbc
      determined by the reference method correlated well with values obtained with the
      Harleco apparatus using plasma (coefficient of correlation 0.804) or whole blood
      (cc = 0.565). (3) On the basis of sensitivity and specificity, the Harleco
      apparatus diagnosed alkalosis as reliably as acidosis. (4) The values determined
      in whole blood were not accurate. (5) The amount of plasma required can be
      obtained in practice using a micro-centrifuge. (6) Results obtained using a self
      prepared reagent were not significantly different from those obtained using the
      commercially available reagent. (7) Use of a second standard with a bicarbonate
      concentration close to the sample value did not yield significantly different
      results than use of a single standard of 25 mmol/l. (8) Increasing the reaction
      time from 30 sec (according to instructions) to 60 or 90 sec did not yield
      significantly better results. It is concluded that the Harleco apparatus is a
      simple, quick, cheap, sufficiently reliable and practical alternative to
      convential methods for the determination of total CO2 in plasma of cattle.

PMID- 9626744
TI  - [Occurrence of white liver dis in lambs in Switzerland].
AB  - The white liver disease was first observed in the canton of Berne in 1985. Until
      1995 we could observe the outbreak of the disease in seven flocks. The first
      clinical signs were anorexia, then delayed growth, weight loss and finally
      cachexy. The animals showed photosensitivity on ears, eyelids and nose. A
      hematological and blood biochemical examination revealed a mild normochrome,
      normocytic anemia as well as a significant elevation of GGT and a mild elevation
      of AST values. By examining the swollen grey-white to yellow livers
      histologically we could find a mostly pronounced, primarily panacinar,
      degenerative fatty degeneration of the liver, ceroid pigment in the macrophages,
      biliary hyperplasia as well as a secondary periportal hepatitis.

PMID- 9626745
TI  - [Diagnostic value of total plasma levels of bile acids and ammonia in liver
      diseases in sheep].
AB  - For the estimation of the diagnostic value of plasma concentrations of total bile
      acids and ammonia in liver disease healthy controls (n = 23) as well as animals
      sick with different diseases were examined. The reference values for total bile
      acids and ammonia in the plasma of sheep range from 18-166 mumol/l and 15-64
      mumol/l, respectively. While animals with chronic copper poisoning (n = 18),
      vitamin E/selenium deficiency (n = 15) and with diseases not affecting the liver
      (n = 8) did not show significant differences in concentrations of total bile
      acids and ammonia from those of the healthy controls, this could be proven for
      animals with severe hepatopathy or hepatoencephalopathy. Furthermore, some of the
      latter group showed increased ammonia concentrations in the liquor
      cerebrospinalis and multifocal vacuolation of the central nervous system. The
      determination of total bile acids and ammonia in the diagnosis of liver disease
      in sheep would also be useful. The hepatoencephalic syndrome should therefore be
      considered as possible differential diagnosis in animals showing neurological
      signs.

PMID- 9626746
TI  - [Importance of oral iron supplementation in piglets in the first hours of life].
AB  - An early supply of iron is essential for newborn piglets due to the
      predisposition to anaemia in neonates of this species. The present study shows
      that iron can be given orally if a suitable preparation is used. After oral
      administration of iron within the first six hours of life, hemoglobin and packed
      cell volume are higher on the 10th day of life compared to the second. Also, the
      percentage of anaemia is significantly lower in piglets with oral iron
      supplementation than in piglets given iron injections on the third day of life.
      The oral iron preparation investigated in this study is therefore superior to
      other preparations. However, a second dose of iron on the 10th day of life is
      necessary independent from mode of administration of the first iron dose. The
      second dose is always given via injection due to insufficient intestinal
      absorption of iron in the 10-day-old piglet.

PMID- 9626747
TI  - [Equine Cushing syndrome (ECS). Case report, review of its diagnosis and therapy
      and substantial differences from Cushing syndrome in dogs].
AB  - Equine and canine Cushing's syndrome, both of which are the result of elevated
      cortisol levels, show some different pathogenetical and clinical features and
      require different therapeutical approaches. In older horses the equine Cushing's
      syndrome (ECS) is not uncommon. Nearly all cases result from excessive hormone
      production in cells of the pars intermedia of the pituitary. Besides elevated
      levels of adrenocorticotrope hormone (ACTH), high peripheral levels of pro
      opiomelanocortin, beta-endorphines and alpha-melanocyte-stimulating hormone can
      be measured. In middle-aged and geriatric dogs, Cushing's syndrome is the most
      frequently diagnosed endocrinologic abnormality. 80-85% of cases are pituitary
      dependent and 15-20% are caused by cortisol producing tumors of the adrenals. 90%
      of pituitary lesions can be identified as adenomas, which are localised in most
      cases in the pars distalis of the gland, but may occur rarely in the pars
      intermedia, too. Clinical symptoms in both species are characterised by wasting
      despite good appetite or polyphagia, reduction of muscle mass with altered fat
      deposition and lethargy. Whereas polydipsia/polyuria is a very common feature in
      dogs with Cushing's syndrome, in horses it is almost invariably a sign of
      concurrent secondary diabetes mellitus. A typical symptom in ECS is a
      continuously growing haircoat (hirsutism), whereas in canine Cushing's syndrome
      generalised alopecia may bring the owner to consult a veterinarian. The symptoms
      and diagnostic procedures in a 33-year-old mare are described. Useful diagnostic
      tests are reviewed with special attention to species differences in reacting to
      them. The therapeutic approach with dopamine-agonists such as bromocriptine and
      pergolide as well as cyproheptadine to ECS is reviewed.

PMID- 9626748
TI  - [Verotoxin production and adhesion genes of E. coli isolates from commercial
      poultry and psittacines: detection by PCR].
AB  - A total of 101 E. coli isolates from commercial poultry, companion psittacine
      birds and psittacine faecal samples were tested by the PCR technique for the
      presence of genes coding for verotoxin (slt I and slt II) production and adhesion
      to intestinal cells (eaeA gene). The O 157:H 7 strain EDL 933 served as positive
      control. Verotoxin production was assessed in Vero cell cultures. One E. coli
      isolate showed both alpha-haemolysis and enterohaemolysis (haemolysin production)
      but no gene for verotoxin production. All other isolates were negative for slt I,
      slt II and eaeA genes.

PMID- 9626749
TI  - Hepatic glutathione and glutathione S-conjugate transport mechanisms.
AB  - Glutathione (GSH) plays a critical role in many cellular processes, including the
      metabolism and detoxification of oxidants, metals, and other reactive
      electrophilic compounds of both endogenous and exogenous origin. Because the
      liver is a major site of GSH and glutathione S-conjugate biosynthesis and export,
      significant effort has been devoted to characterizing liver cell sinusoidal and
      canalicular membrane transporters for these compounds. Glutathione S-conjugates
      synthesized in the liver are secreted preferentially into bile, and recent
      studies in isolated canalicular membrane vesicles indicate that there are
      multiple transport mechanisms for these conjugates, including those that are
      energized by ATP hydrolysis and those that may be driven by the electrochemical
      gradient. Glutathione S-conjugates that are relatively hydrophobic or have a
      bulky S-substituent are good substrates for the canalicular ATP-dependent
      transporter mrp2 (multidrug resistance-associated protein 2, also called cMOAT,
      the canalicular multispecific organic anion transporter, or cMrp, the canalicular
      isoform of mrp). In contrast with the glutathione S-conjugates, hepatic GSH is
      released into both blood and bile. GSH transport across both of these membrane
      domains is of low affinity and is energized by the electrochemical potential.
      Recent reports describe two candidate GSH transport proteins for the canalicular
      and sinusoidal membranes (RcGshT and RsGshT, respectively); however, some
      concerns have been raised regarding these studies. Additional work is needed to
      characterize GSH transporters at the functional and molecular level.

PMID- 9626750
TI  - Functional re-evaluation of the putative glutathione transporters, RcGshT and
      RsGshT.
AB  - Transport systems that mediate glutathione (GSH) efflux from hepatocytes into
      blood plasma and bile have been characterized extensively in sinusoidal and
      canalicular membrane vesicles, and recent reports describe two candidate GSH
      transport proteins: the rat sinusoidal GSH transporter (RsGshT) and rat
      canalicular GSH transporter (RcGshT). However, studies in our laboratory have
      been unable to confirm the function of these gene products. Xenopus laevis
      oocytes injected with either rat liver mRNA, the cRNA for RcGshT or the cRNA for
      RsGshT did not transport GSH at a higher rate than water-injected oocytes, when
      measured either as 3H-GSH uptake or efflux, at low or high GSH concentrations, or
      in the presence or absence of acivicin to inhibit gamma-glutamyltransferase
      activity. In contrast, transport of 3H-taurocholate was markedly accelerated in
      oocytes injected with rat liver mRNA or the cRNA for the Na(+)-taurocholate
      cotransporting polypeptide (Ntcp), confirming the integrity of the mRNA and the
      viability of the oocytes. Northern blot analysis failed to detect an RcGshT
      transcript in rat liver total RNA or rat liver mRNA. Of significance, the RcGshT
      and RsGshT cDNA sequences are similar to those found in the Escherichia coli K-12
      genome, indicating possible cloning artifacts. Further studies are needed to
      resolve this discrepancy, and to isolate and characterize hepatic GSH transport
      proteins.

PMID- 9626751
TI  - Recent advances in the field of renal potassium excretion: what can we learn from
      potassium channels?
AB  - Potassium channels in the apical and basolateral membranes of tubule cells serve
      several important functions. They contribute to the generation of the cell
      negative potential, mediate volume reductions following cell swelling and play a
      key role in secretion of potassium in both the thick ascending limb of Henle's
      loop and principal tubule cells of the initial and cortical collecting tubules.
      Secretion of potassium occurs via a well-defined class of potassium channels
      distinguished by their low single channel conductance, mild inward rectification,
      high sensitivity to inhibition by low pH, millimolar concentrations of ATP,
      arachidonic acid and PKC, and stimulation by vasopressin and pretreatment with a
      high potassium diet. Genes encoding several isoforms of this channel have been
      cloned and the proteins located to the apical membranes of cells lining the thick
      ascending limb of Henle's loop and the collecting tubules, and progress made
      concerning their structure-function relationship.

PMID- 9626752
TI  - Hepatic protoporphyrin metabolism in patients with advanced protoporphyric liver
      disease.
AB  - Protoporphyria is a genetic disorder in which liver damage is caused by the toxic
      effect of protoporphyrin accumulation in the liver. In this study protoporphyrin
      was measured in the resected livers of 7 patients who had liver transplantation
      and an additional patient from whom liver tissue was obtained post mortem.
      Comparison of liver, erythrocyte and serum protoporphyrin levels demonstrated a
      marked gradient between these compartments: erythrocyte, 5781 +/- 655
      micrograms/dl; serum, 384 +/- 102 micrograms/dl; liver 377,238 +/- 55,568
      micrograms/100 gm wet weight, (mean +/- SE). Protoporphyrin levels in bile of 3
      patients were 55,559, and 1,153 micrograms/dl, indicating a gradient between
      liver and bile as well. Examination of the livers by polarization microscopy and
      electron microscopy demonstrated protoporphyrin pigment crystals. In one patient
      who had recurrent liver disease after transplantation, the protoporphyrin
      concentration in the graft at the time of death was similar to that in the
      resected liver. These data indicate that liver protoporphyrin levels in patients
      with advanced protoporphyric liver disease are much higher than levels in blood
      and bile, in part because protoporphyrin forms crystalline deposits in liver
      tissue. Thus, progressive hepatic accumulation of protoporphyrin occurs in the
      face of impaired biliary excretion. An intrinsic defect in hepatic excretion of
      protoporphyrin is probably not necessary for this condition to develop because
      liver disease can occur in the graft following transplantation.

PMID- 9626753
TI  - Electrogenicity of Na(+)-coupled bile acid transporters.
AB  - The Na(+)-bile acid cotransporters NTCP and ASBT are largely responsible for the
      Na(+)-dependent bile acid uptake in hepatocytes and intestinal epithelial cells,
      respectively. This review discusses the experimental methods available for
      demonstrating electrogenicity and examines the accumulating evidence that coupled
      transport by each of these bile acid transporters is electrogenic. The evidence
      includes measurements of transport-associated currents by patch clamp
      electrophysiological techniques, as well as direct measurement of fluorescent
      bile acid transport rates in whole cell patch clamped, voltage clamped cells. The
      results support a Na+:bile acid coupling stoichiometry of 2:1.

PMID- 9626754
TI  - Effects of bile acids on hepatocellular signaling and secretion.
AB  - Bile acids modulate hepatocellular signaling pathways in vitro at physiological
      concentrations. The present paper provides a brief overview of the effects of
      bile acids on three key messengers in liver cells: cytosolic free calcium,
      protein kinase A and protein kinase C.

PMID- 9626755
TI  - Endocrine and paracrine calcium signaling in bile duct cells.
AB  - Bile duct cells play an important role in maintaining, modifying and augmenting
      bile flow. It is well established that cyclic AMP (cAMP) is an important second
      messenger for secretion in these cells, but less is known about cytosolic Ca2+
      (Ca2+i). Here we review evidence that ATP and acetylcholine (ACh) are Ca2+i
      agonists for bile duct cells, and that these agonists increase Ca2+i through
      inositol 1,4,5-trisphosphate (InsP3). We also review data suggesting that
      hepatocytes have the ability to secrete ATP, so that they may serve as a
      paracrine source for this signaling molecule in vivo. Finally, we compare the
      effects of cAMP and Ca2+i on secretion, both in isolated bile duct units and
      isolated hepatocyte couplets. Implications and future directions for studying the
      role of Ca2+i in bile ductular secretion are discussed.

PMID- 9626756
TI  - Molecular regulation of sinusoidal liver bile acid transporters during
      cholestasis.
AB  - Impairment of the hepatic transport of bile acids and other organic anions will
      result in the clinically important syndrome of cholestasis. Cloning of a number
      of specific hepatic organic anion transporters has enabled studies of their
      molecular regulation during cholestasis. The best characterized transport system
      is a 50-51 kDa sodium-dependent taurocholate cotransporting polypeptide (ntcp),
      which mediates the sodium-dependent uptake of conjugated bile acids at the
      sinusoidal plasma membrane of hepatocytes. Under physiologic conditions and after
      depletion of biliary constituents, ntcp remains constitutively expressed
      throughout the liver acinus. However, both function and expression of ntcp are
      rapidly down-regulated in rat liver in various models of experimental
      cholestasis, such as cholestasis induced by common bile duct ligation, estrogen,
      endotoxin or cytokine treatment. In addition to ntcp, the sinusoidal organic
      anion transporting polypeptide oatp-1 is also down-regulated at the protein and
      steady-state mRNA levels in estrogen-cholestasis, but does not affect sodium
      independent uptake of taurocholate. The regulation of a recently cloned member of
      the organic anion transporter family (oatp-2), which is highly expressed in
      liver, remains to be studied under cholestatic conditions.

PMID- 9626758
TI  - Mechanisms of hepatic transport of cyclosporin A: an explanation for its
      cholestatic action?
AB  - The hepatic transport of the immunosuppressive Cyclosporin A (CyA) was studied
      using liposomal phospholipid membranes, freshly isolated rat hepatocytes and bile
      canalicular plasma membrane vesicles from rat liver. The Na(+)-dependent,
      saturable uptake of the bile acid 3H-taurocholate into isolated rat liver cells
      was apparently competitively inhibited by CyA. However, the uptake of CyA into
      the cells was neither saturable, nor temperature-dependent nor Na(+)-dependent,
      nor could it be inhibited by bile salts or CyA-derivatives, indicating passive
      diffusion. In steady state depolarization fluorescence studies, CyA caused a
      concentration-dependent decrease of anisotropy, indicating a membrane fluidizing
      effect. Ion flux experiments demonstrated that CyA dramatically increases the
      permeability of Na+ and Ca2+ across phospholipid membranes in a dose- and time
      dependent manner, suggesting a iontophoretic activity that might have a direct
      impact on cellular ion homeostasis and regulation of bile acid uptake.
      Photoaffinity labeling with a [3H]-labeled photolabile CyA-derivative resulted in
      the predominant incorporation of radioactivity into a membrane polypeptide with
      an apparent molecular weight of 160,000 and a minor labeling of polypeptides with
      molecular weights of 85,000-90,000. In contrast, use of a photolabile bile acid
      resulted in the labeling of a membrane polypeptide with an apparent molecular
      weight of 110,000, representing the bile canalicular bile acid carrier. The
      photoaffinity labeling as well as CyA transport by canalicular membrane vesicles
      were inhibited by CyA and the p-glycoprotein substrates daunomycin and PSC-833,
      but not by taurocholate, indicating that CyA is excreted by p-glycoprotein. CyA
      uptake by bile canalicular membrane vesicles was ATP-dependent and could not be
      inhibited by taurocholate. CyA caused a decrease in the maximum amount of bile
      salt accumulated by the vesicles with time. However, initial rates of [3H]
      taurocholate uptake within the first 2.5 min remained unchanged at increasing CyA
      concentrations. In summary, the data indicate that CyA does not directly interact
      with the hepatic bile acid transport systems. Its cholestatic action may rather
      be the result of alterations in membrane fluidity, intracellular effects and an
      interaction with p-glycoprotein.

PMID- 9626757
TI  - Molecular alterations of canalicular transport systems in experimental models of
      cholestasis: possible functional correlations.
AB  - The discovery of unidirectional, ATP-dependent canalicular transport systems
      (also termed "export pumps") for bile salts, amphiphilic anionic conjugates,
      lipophilic cations, and phospholipids has opened new opportunities for
      understanding biliary physiology and the pathophysiology of cholestasis. In
      addition, ATP-independent canalicular transport systems for glutathione and
      bicarbonate contribute to (bile acid-independent) bile formation. Canalicular
      excretion of bile salts and several non-bile acid organic anions is impaired in
      various experimental models of cholestasis. Recent cloning of several canalicular
      transport systems now facilitates studies on their molecular regulation in
      cholestasis. Although the picture is far from complete, experimental evidence now
      exists that decreased or even absent expression of canalicular transport proteins
      may explain impaired transport function resulting in hyperbilirubinemia and
      cholestasis. With the increasing availability of molecular probes for these
      transport systems in humans, new information on the molecular regulation of
      canalicular transport proteins in human cholestatic liver diseases is beginning
      to emerge and should bring new insights into their pathophysiology and treatment.
      This article gives an overview on molecular alterations of canalicular transport
      systems in experimental models of cholestasis and discusses the potential
      implications of these changes for the pathophysiology of cholestasis.

PMID- 9626759
TI  - The use of synthetic analogues of Arg-Gly-Asp (RGD) and soluble receptor of tumor
      necrosis factor to prevent acute and chronic experimental liver injury.
AB  - In chronic viral hepatitis, autoimmune hepatitis, and some chronic cholestatic
      liver diseases, T-lymphocytes serve as effector cells of the immunostimulatory
      processes. Cellular interactions of immune cells with extracellular matrix (ECM)
      components are regulated primarily via the beta 1 subfamily of integrin
      receptors. The target epitope of several such integrin receptors is the Arg-Gly
      Asp (RGD) sequence, a cell adhesion motif shared by several matrix-associated
      adhesive glycoproteins. We review the use of synthetic nonpeptidic analogues of
      RGD and of soluble receptor of tumor necrosis factor (TNF)-alpha in the
      prevention of immune-mediated, concanavalin A-induced liver damage in mice and of
      RGD analogues in inhibiting the development of liver cirrhosis in rats. The
      concanavalin A-induced elevation of serum transaminases and TNF-alpha, and the
      infiltration of liver tissue by inflammatory cells, were inhibited by
      pretreatment of the mice with the synthetic RGD mimetics and soluble TNF
      receptor. In rats, the progression of thioacetamide-induced liver cirrhosis was
      markedly inhibited by the coadministration of the RGD mimetic SF-6,5. The
      compounds described here may be examined therapeutically for pathological
      conditions in the liver, manifested as necroinflammation, cholestasis and
      fibrosis.

PMID- 9626760
TI  - Biliary secretion of endotoxin and pathogenesis of primary biliary cirrhosis.
AB  - Previous studies suggested endotoxin, derived from the intestine through the
      portal blood to the liver, was predominantly metabolized by Kupffer cells. In the
      present study, fluorescent-labeled endotoxin injected into the rat portal vein
      was demonstrated not only in Kupffer cells but also in hepatocytes. Furthermore a
      great amount of labeled endotoxin was recovered in bile. In the livers of
      patients with primary biliary cirrhosis (PBC), immunohistochemistry demonstrated
      significant retention of endotoxin in the biliary epithelial cells, and treatment
      with ursodeoxycholic acid significantly reduced the retention in those cells. The
      study for detection of apoptosis demonstrated increased rates of apoptosis in
      hepatocytes and biliary epithelial cells in PBC liver, and the rate of apoptosis
      in biliary epithelial cells was significantly reduced after treatment with
      ursodeoxycholic acid. Immunohistochemistry in PBC liver demonstrated significant
      reduction of fluorescence intensity for a 7H6 antigen in biliary epithelial
      cells, indicating the increased paracellular permeability of bile ducts, because
      cellular immunolocalization of that antigen has been shown to be inversely
      correlated with the paracellular permeability of the tight junction. These
      results suggest that, in biliary epithelial cells, retention of endotoxin,
      increased apoptosis, and increased permeability of tight junctions may be
      involved in the pathogenesis of PBC.

PMID- 9626761
TI  - Role of the neuropeptide, bombesin, in bile secretion.
AB  - Since ancient times, bile secretion has been considered vital for maintaining
      health. One of the main functions of bile secretion is gastric acid
      neutralization with biliary bicarbonate during a meal or Pavlovian response.
      Although the liver has many extrinsic and intrinsic nerve innervations, the
      functional role of these nerves in biliary physiology is poorly understood. To
      understand the role of neural regulation in bile secretion, our recent studies on
      the effect of bombesin, a neuropeptide, on bile secretion and its underlying
      mechanisms will be reviewed. Using isolated perfused rat livers (IPRL) from both
      normal and 2 week bile duct ligated rats, as well as hepatocyte couplets and
      isolated bile duct units (IBDU) from normal rat livers, bombesin was shown to
      stimulate biliary bicarbonate and fluid secretion from bile ducts. Detailed pH
      studies indicated that bombesin stimulated the activity of Cl-/HCO3- exchanger,
      which was counterbalanced by a secondary activation of electrogenic Na+/HCO3-
      symport. Quantitative videomicroscopic studies showed that bombesin-stimulated
      fluid secretion in IBDU was dependent on Cl- and HCO3- in the media, anion
      exchanger(s), Cl- and K+ channels, and carbonic anhydrase, but not on the
      microtubular system. Furthermore, this bombesin response is inhibited by
      somatostatin but not substance P. Finally, studies of secondary messengers in
      isolated cholangiocytes and IBDU indicated that bombesin had no effect on
      intracellular cAMP, cGMP, or Ca++ levels in cholangiocytes. These results provide
      evidence that neuropeptides such as bombesin can directly stimulate fluid and
      bicarbonate secretion from cholangiocytes by activating luminal Cl-/HCO3-
      exchange, but by different mechanisms from those established for secretin. These
      findings, in turn, suggest that neuropeptides may play an important regulatory
      role in biliary transport and secretion. Thus, this neuropeptidergic regulation
      of bile secretion may provide a plausible mechanism for the bicarbonate-rich
      choleresis seen with meals or Pavlovian response.

PMID- 9626762
TI  - Hormonal regulation of bicarbonate secretion in the biliary epithelium.
AB  - Bicarbonate excretion in bile is a major function of the biliary epithelium. It
      is driven by the apically located Cl-/HCO3- exchanger which is functionally
      coupled with a cAMP-dependent Cl- channel (CFTR). A number of hormones and/or
      neuropeptides with different mechanisms and at different intracellular levels
      regulate, in concert, the processes underlying bicarbonate excretion in the
      biliary epithelium. Secretin induces a bicarbonate rich choleresis by stimulating
      the activity of the Cl-/HCO3- exchanger by cAMP and protein kinase A mediated
      phosphorylation of CFTR regulatory domain. Protein phosphatase 1/2A are involved
      in the run-down of secretory stimulus after secretin removal. Acetylcholine
      potentiates secretin-choleresis by inducing a Ca(++)-calcineurin mediated
      "sensitization" of adenyl cyclase to secretin. Bombesin and vasoactive intestinal
      peptide also enhance the Cl-/HCO3- exchanger activity, but the intracellular
      signal transduction pathway has not yet been defined. Somatostatin and gastrin
      inhibit basal and/or secretin-stimulated bicarbonate excretion by down-regulating
      the secretin receptor and decreasing cAMP intracellular levels induced by
      secretin.

PMID- 9626763
TI  - Transport systems in cholangiocytes: their role in bile formation and
      cholestasis.
AB  - Formation of bile requires the coordinated function of two epithelial cell types:
      hepatocytes, that are responsible for secretion of the major osmolytes and
      biliary constituents and cholangiocytes that regulate the fluidity and alkalinity
      of bile through secretion of osmolytes such as Cl- and HCO3- Studies in isolated
      cholangiocyte preparations have elucidated the basic transport mechanisms
      involved in constitutive and stimulated secretory activities in the biliary
      epithelium. Basolateral Na+/H+ exchanger and Na+:HCO3- symporter mediate HCO3-
      uptake, while an apical cAMP-activated Cl-/HCO3- exchanger secretes bicarbonate
      into the lumen. Cholangiocytes also possess a cAMP-stimulated Cl- conductance
      (CFTR) and a Ca-activated Cl- channel, both likely located at the apical
      membrane. Cholangiocyte secretory functions are regulated by a complex network of
      hormones mainly acting via the cAMP system. In addition, recent data indicate
      that part of the regulation of ductular secretion may take place at the apical
      membrane of the cholangiocyte through factors present into the bile, such as ATP,
      bile acids and glutathione. Primary damage to the biliary epithelium is the cause
      of several chronic cholestatic disorders (cholangiopathies). From a
      pathophysiological point of view, common to all cholangiopathies is the
      coexistance of cholangiocyte death and proliferation and various degrees of
      portal inflammation and fibrosis. Cholestasis dominates the clinical picture and,
      pathophysiologically, may initiate or worsen the process. Alterations in biliary
      electrolyte transport could contribute to the pathogenesis of cholestasis in
      primary bile duct diseases. Cystic Fibrosis-related liver disease represents an
      example of biliary cirrhosis secondary to a derangement of cholangiocyte ion
      transport. Most primary cholangiopaties recognize an immune-mediated
      pathogenesis. Cytokines, chemokines, and proinflammatory mediators released in
      the portal spaces or produced by the cholangiocyte itself, likely activate
      fibrogenesis, stimulate apoptotic and proliferative responses, and alter the
      transport functions of the epithelium.

PMID- 9626764
TI  - Regulation of organic anion transport in the liver.
AB  - In several liver diseases the biliary transport is disturbed, resulting in, for
      example, jaundice and cholestasis. Many of these symptoms can be attributed to
      altered regulation of hepatic transporters. Organic anion transport, mediated by
      the canalicular multispecific organic anion transporter (cmoat), has been
      extensively studied. The regulation of intracellular vesicular sorting of cmoat
      by protein kinase C and protein kinase A, and the regulation of cmoat-mediated
      transport in endotoxemic liver disease, have been examined. The discovery that
      the multidrug resistance protein (MRP), responsible for multidrug resistance in
      cancers, transports similar substrates as cmoat led to the cloning of a MRP
      homologue from rat liver, named mrp2. Mrp2 turned out to be identical to cmoat.
      At present there is evidence that at least two mrp's are present in hepatocytes,
      the original mrp (mrp1) on the lateral membrane, and mrp2 (cmoat) on the
      canalicular membrane. The expression of mrp1 and mrp2 in hepatocytes appears to
      be cell-cycle-dependent and regulated in a reciprocal fashion. These findings
      show that biliary transport of organic anions and possibly other canalicular
      transport is influenced by the entry of hepatocytes into the cell cycle. The
      cloning of the gene for cmoat opens up new possibilities to study the regulation
      of hepatic organic anion transport.

PMID- 9626766
TI  - Is intracellular pH and/or intracellular bicarbonate a determinant of bile salt
      independent canalicular bile formation? The subject revisited.
AB  - Canalicular bile formation is a complex process that involves basolateral and
      apical cell membrane transport, paracellular transport and vesicular transport,
      all of which may be subject to regulation by pH. We review the concept that
      apical cell membrane bicarbonate secretion promotes bile salt independent
      canalicular bile formation. We show that the presence of paracellular electrolyte
      transport imposes a severe restriction in interpreting data from ion substitution
      experiments aimed at demonstrating pH or bicarbonate dependent bile formation.
      Furthermore, we report on experiments that all show stimulation of bile flow
      under three disparate experimental conditions: i) intracellular alkalinization in
      the absence of [HCO3-]i or associated with a decrease of [HCO3-]i, ii)
      intracellular alkalinization with an increase of [HCO3-]i, and iii) intracellular
      acidification with increase of [HCO3-]i. It is suggested that both, intracellular
      pH and intracellular bicarbonate may modulate canalicular bile salt independent
      bile formation, but it remains conjectural which mechanism is the prevailing one
      under a given experimental setting.

PMID- 9626765
TI  - Cholyllysyl fluroscein and related lysyl fluorescein conjugated bile acid
      analogues.
AB  - There have been attempts to couple bile acids to fluorescein to permit their
      visualization during studies of physiology and pathophysiology. Although
      conjugation has been achieved by many, the product differed in many respects from
      the parent bile acid congener. We describe lysylfluorescein conjugated bile acid
      analogues (LFCBAA) synthesized in our laboratory as model divalent "unipolar"
      molecules. We have determined LFCBAA properties including their water:octanol
      partition coefficient, HPLC retention time and critical micellar concentration
      and compared them with their parent bile acid congeners. Cholyl lysylfluorescein
      (CLF) and lithocholyl lysylfluoroscein (LLF) have properties similar to
      cholylglycine (CG) and glycolithocholate (GLC), respectively. In human and rat
      hepatocytes uptake of CLF follows Michaelis-Menten kinetics with K(m) and Vmax
      similar to CG. Biliary excretion rates of CLF and LLF closely resemble those of
      CG and GLC in both normal and mutant TR- rats which lack the multiorganic anion
      transporter (MOAT), strongly supporting the notion that CLF and LLF are
      substrates for the canalicular bile salt transporter (cBST). The close similarity
      of hepatocyte uptake and biliary secretion of these LFCBAA and their parent bile
      acid congeners makes them potentially useful probes for the intracellular
      visualization of bile salt movement and deposition in various models of bile
      formation and secretion.

PMID- 9626767
TI  - Recent insights into neurofibromatosis type 1: clear genetic progress.

PMID- 9626768
TI  - Complementary DNA libraries and neurological disease.

PMID- 9626769
TI  - The GTP cyclohydrolase I gene in Russian families with dopa-responsive dystonia.
AB  - OBJECTIVE: To search for mutations in the GTP cyclohydrolase I (GCH-I) gene in a
      set of Russian families with dopa-responsive dystonia (DRD). DESIGN: Six large
      families with 54 affected family members and 2 patients with sporadic DRD were
      examined. Mutation screening was performed using single-strand conformation
      polymorphism analysis followed by direct sequencing of the presumably mutated
      exons, in patients whose results showed a normal pattern on single-strand
      conformation polymorphism analysis, the entire coding region of the GCH-I gene
      was sequenced. RESULTS: Three new heterozygote point mutations located within
      exons 1, 2, and 4 of the GCH-I gene were identified in 3 families with autosomal
      dominant inheritance. All these mutations are predicted to cause amino acid
      changes in the highly conserved regions of the gene. In patients from 3 other
      families and in both patients with sporadic DRD, no alterations in the translated
      portion of the GCH-I gene were observed. CONCLUSIONS: Mutations in the coding
      region of the GCH-I gene account for a significant fraction (up to half) of the
      patients with a typical clinical picture of DRD. None of the mutations in the GCH
      I gene described so far were detected more than once, which precludes the
      possibility of creating simple DNA testing procedures for routine clinical
      practice.

PMID- 9626770
TI  - Increased production of tumor necrosis factor alpha, and not of interferon gamma,
      preceding disease activity in patients with multiple sclerosis.
AB  - OBJECTIVE: To study whether tumor necrosis factor (TNF) alpha or interferon (IFN)
      gamma production by stimulated white blood cells precedes or accompanies clinical
      and magnetic resonance imaging signs of disease activity in patients with
      multiple sclerosis. DESIGN: Prospective study with a follow-up of 9 months.
      SETTING: Patients visiting an outpatient university clinic. PATIENTS: The 30
      Amsterdam-based patients (28 completing all evaluations) participating in a
      multicenter, randomized, placebo-controlled, double-blind trial of a chimeric
      anti-CD4 antibody in the treatment of active relapsing-remitting and secondary
      progressive multiple sclerosis. Patients in both treatment arms were included,
      because for these patients anti-CD4 treatment in this study did not affect TNF
      alpha and IFN-gamma production and did not reduce signs of disease activity on
      magnetic resonance imaging. MAIN OUTCOME MEASURE: Distribution of classes of TNF
      alpha and IFN-gamma production (expressed as z scores) in patients with or
      without clinical or magnetic resonance imaging signs of disease activity.
      RESULTS: One month preceding exacerbations of multiple sclerosis, there was a
      shift toward higher z scores of TNF-alpha production (P<.05), but not of IFN
      gamma production. There was no statistically significant relationship between IFN
      gamma and TNF-alpha production and magnetic resonance imaging markers of multiple
      sclerosis activity. CONCLUSION: The production of TNF-alpha, and not of IFN
      gamma, is significantly higher in patients with multiple sclerosis before
      exacerbations than in patients with stable disease. Although present, this
      relationship is too weak to use TNF-alpha production as a surrogate marker of
      disease activity in multiple sclerosis.

PMID- 9626771
TI  - Awareness of involuntary movements in Huntington disease.
AB  - OBJECTIVE: To determine why patients with Huntington disease are apparently
      unaware of their involuntary movements. DESIGN: Correlative study using a
      subjective report questionnaire of physical symptoms and objective measures of
      neurologic and cognitive dysfunction. PATIENTS: Forty patients with Huntington
      disease attending a regional Huntington disease clinic. RESULTS: Patients were
      poor at reporting experiential symptoms of involuntary movements. There was no
      relationship between self-report of these symptoms and objective indices of motor
      dysfunction or severity of cognitive impairment. Patients could, however, report
      secondary consequences of their movement disorder, which correlated highly with
      nonchoreic indices of motor dysfunction. CONCLUSIONS: Patients with Huntington
      disease have impaired subjective experience of chorea. Denial of symptoms is
      likely to have a physiological basis and is not a secondary consequence of
      patients' cognitive impairment or a psychological defense against a debilitating
      disease.

PMID- 9626772
TI  - Apolipoprotein E epsilon4 allele and familial aggregation of Alzheimer disease.
AB  - OBJECTIVE: To investigate the relationship among risk for Alzheimer disease (AD),
      familial aggregation of AD, and the apolipoprotein E (apoE) epsilon4 allele in
      first-degree relatives of probands with AD and known apoE genotype. PATIENTS: Two
      hundred ninety subjects fulfilling the criteria of the National Institute of
      Neurological Communicative Disease and Stroke-Alzheimer's Disease and Related
      Disorders Association for probable AD were ascertained from March 1, 1992, to
      December 31, 1996, through consecutive admissions in several university
      hospitals. DESIGN AND METHODS: Family data were collected on 1176 first-degree
      relatives (parents and siblings), aged 40 to 90 years. Most living relatives
      underwent a clinical examination, whereas we relied on family history for
      clinical data for deceased or unavailable relatives. First, we conducted standard
      survival analyses to estimate cumulative lifetime risk (LTR) for AD among
      relatives and to investigate for sex and apoE genotype effects on LTR. Then, we
      assessed to what extent clustering of secondary AD could be explained by the apoE
      epsilon4 allele by deriving the expected proportions of relatives with 0, 1, or 2
      apoE epsilon4 alleles conditionally on the proband's genotype. RESULTS:
      Cumulative LTR for AD among first-degree relatives increased significantly with
      the number of epsilon4 alleles present in the proband. By 90 years of age, LTRs
      in relatives of probands with epsilon3/epsilon3, epsilon3/epsilon4, and
      epsilon4/epsilon4 genotypes were 29.2%, 46.1%, and 61.4%, respectively.
      Significant sex-by-apoE genotype interaction effects on LTR were observed. Women
      had about a 2-fold higher risk for AD than men among relatives of epsilon4
      carriers but not among relatives of non-epsilon4 carriers. The predicted
      proportion of epsilon4 carriers in relatives of probands with epsilon3/epsilon3
      genotype remains about 50% lower than the corresponding LTR for AD, indicating
      that familial clustering of AD is largely due to other factors than the apoE
      epsilon4 allele. Although aggregation of AD in families of probands with the
      epsilon4 allele is more prominent, we estimated that AD would not develop in
      about 30% of female and up to 60% of male relatives carrying at least 1 epsilon4
      allele, even by 90 years of age. CONCLUSION: Our results support the hypothesis
      that the apoE epsilon4 allele enhances AD susceptibility, but putative factors
      enhancing risk for AD remain to be found.

PMID- 9626773
TI  - Anticardiolipin antibodies are frequently present in patients with idiopathic
      intracranial hypertension.
AB  - BACKGROUND: Anticardiolipin antibodies (ACL-Ab) are associated with various
      neurologic syndromes, but idiopathic intracranial hypertension (IIH) has only
      rarely been reported in this context. OBJECTIVES: To delineate the frequency and
      clinical and radiological features of, as well as the cause-and-effect
      relationship between, ACL-Ab and IIH. METHODS: We analyzed the medical records of
      patients with IIH hospitalized between January 1989 and September 1995. All
      patients underwent magnetic resonance imaging or magnetic resonance venography or
      angiography. Excluded were patients with intracranial hypertension due to dural
      sinus thrombosis or traumatic, structural, neoplastic, or infectious disorders.
      Patients who were found on at least 2 separate occasions to have increased IgG
      titers of ACL-Ab were identified and compared with patients without ACL-Ab.
      RESULTS: Six (43%) of 14 patients with IIH had ACL-Ab. No differences in
      clinical, laboratory, or radiological variables could be found between patients
      with and without ACL-Ab. Only 3 of the 11 ACL-Ab-positive patients had previous
      systemic or neurologic abnormalities associated with ACL-Ab. CONCLUSIONS:
      Anticardiolipin antibodies may cause IIH through mechanisms unrelated to major
      venous thrombosis. Idiopathic intracranial hypertension is frequently associated
      with ACL-Ab and can be the presenting symptom of the antiphospholipid syndrome.
      There are no major clinical, laboratory, or radiological features that
      distinguish between patients with IIH with and without ACL-Ab.

PMID- 9626774
TI  - Diagnostic criteria for essential tremor: a population perspective.
AB  - BACKGROUND: Prevalence estimates vary 2750-fold among the 20 studies of essential
      tremor (ET). It is not clear how the choice of diagnostic criteria affects
      research results. OBJECTIVE: To determine the impact of alternative sets of
      diagnostic criteria on the diagnosis of ET. METHODS: As part of the Washington
      Heights-Inwood Genetic Study of ET (WHIGET), a population-based study of ET, 285
      subjects who include 36 case subjects with probable or definite ET, 34 case
      subjects with possible ET, and 215 normal subjects were interviewed and examined.
      All diagnoses in WHIGET were assigned by 2 neurologists. Ten of the 20 published
      prevalence studies of ET provided diagnostic criteria for ET. Criteria differed
      in terms of requirements for the distribution, duration, and severity of tremor.
      These 10 sets of criteria were then each separately applied to the subjects in
      the WHIGET cohort to determine their impact on the diagnosis of ET. RESULTS:
      Depending on which diagnostic criteria were applied to the WHIGET cohort, the
      proportion of WHIGET case subjects with definite or probable ET who would have
      been diagnosed as having ET was as low as 14% and the proportion of WHIGET normal
      subjects who would have been diagnosed as having ET was as high as 51%.
      Diagnostic criteria that included a positive family history of ET or a lengthy
      duration of tremor would have classified many WHIGET case subjects with ET as
      normal, whereas criteria that did not specify a minimal tremor severity would
      have classified many WHIGET normal subjects as having ET. CONCLUSIONS:
      Alternative sets of diagnostic criteria for ET greatly impact on the diagnosis of
      ET. For population-based studies, information on tremor type and severity rather
      than family history should be included in diagnostic criteria.

PMID- 9626775
TI  - Severity of cognitive impairment in juvenile and late-onset Huntington disease.
AB  - OBJECTIVES: To compare the severity of cognitive impairment among groups of
      patients with different age ranges at the onset of Huntington disease (HD) and to
      evaluate the variable influence of motor and cognitive deficits on functional
      disability across different ages at the onset of HD. DESIGN: Cross-sectional
      multidisciplinary evaluation of patients referred to our institution for care
      related to a possible diagnosis of HD. SETTING: The Huntington disease program in
      the Departments of Neurology and Genetics at the Fundacion Jimenez Diaz, Madrid,
      Spain. PARTICIPANTS: Seventy-one patients with Huntington disease were classified
      into 3 groups depending on age at onset of motor symptoms: juvenile onset, 25
      years of age or younger (group 1, n = 15); adult onset, from 26 to 50 years
      (group 2, n = 43); and late onset, 51 years or older (group 3, n = 13). Age- and
      education-matched controls (n=50) were included to compare cognitive performance
      with patients in groups 1 and 3. MEASURES: Cognitive evaluation encompassed a
      wide neuropsychological battery to assess global cognitive functioning and
      visuospatial, prefrontal, and memory functions. Clinical data included motor and
      functional variables measured by using the Unified Huntington's Disease Rating
      Scale. Genetic analysis determined the number of CAG trinucleotide repeats.
      RESULTS: Patients in group 1 scored 2.9 points and patients in group 3 scored 4.2
      points below their respective controls on the Mini-Mental State Examination.
      Patients in groups 1 and 3 were similarly impaired in verbal memory. Visual
      function was much more impaired in patients in group 3, and prefrontal functions
      were slightly worse in patients in group 1. Cognitive scores were correlated only
      with time of evolution for patients in group 2. Functional scores were not
      significantly different among the 3 groups, but 11 (85%) of the patients in group
      3 were in stage I or II vs 10 (67%) of the patients in group 1. Total functional
      capacity correlated better with the Mini-Mental State Examination score for
      patients in group 3 and with motor deficits (akinesia) and prefrontal dysfunction
      for patients in group 1. The mean+/-SD CAG repeat length decreased from 59.9+/
      12.6 for patients in group 1 to 46.2+/-3.5 for patients in group 2 and 41.7+/-2.6
      for patients in group 3. Longer CAG repeats in the HD study population correlated
      with akinetic features but not with cognitive performance. CONCLUSIONS: Despite
      the much greater genetic defect, cognitive status is slightly better preserved in
      patients with juvenile-onset HD. Cognitive impairment in patients with juvenile-
      and late-onset HD differs in the severity of visual and prefrontal deficits.
      Functional disability in patients with late-onset HD depends more on global
      cognitive status, while in patients with juvenile-onset HD, it is conditioned
      more by motor deficits and prefrontal dysfunction.

PMID- 9626776
TI  - Neuropsychological impairment from acute low-level exposure to carbon monoxide.
AB  - OBJECTIVE: To investigate the effects of acute low-level exposure to carbon
      monoxide on higher cognitive functions in healthy humans. DESIGN: An empirical
      study of the effects of low-level exposure to carbon monoxide on higher cognitive
      functions in young healthy volunteers and a matched nonexposed control group.
      SETTING: A dormitory at the Hebrew University campus in Jerusalem, Israel.
      PARTICIPANTS: Forty-five student volunteers who were exposed to carbon monoxide
      from residential kerosene stoves for 1.5 to 2.5 hours (air carbon monoxide
      concentrations of 17-100 ppm; mean +/- SD, 61 +/- 24 ppm) served as the
      experimental group and 47 nonexposed students served as the control group. MAIN
      OUTCOME MEASURES: A battery of neuropsychological tests was administered to each
      participant including digit span, the revised Wechsler Memory Scale for verbal
      and figural memory, Trail-Making Test parts A and B, digit symbol, block design,
      and the Rey Auditory Verbal Learning Test. RESULTS: Venous blood
      carboxyhemoglobin (Hbco) levels in participants of the study group ranged from
      0.01 to 0.11 (mean +/- SD, 0.04 +/- 0.03) and correlated with air carbon monoxide
      concentrations (r = 0.39; P = .01). The experimental group scored significantly
      lower than controls on the following tests: digit span forward (P = .02), short
      term (P = .008) and long-term semantic memory (P = .008), digit symbol (P =
      .004), block design (P = .009), recall of figural memory (P = .02), and Trail
      Making part A (P = .04). No significant differences were found between the
      experimental and control groups in other tests. CONCLUSIONS: The lower scores on
      neuropsychological tests indicate dysfunctions in memory, new learning ability,
      attention and concentration, tracking skills, visuomotor skills, abstract
      thinking, and visuospatial planing and processing. These dysfunctions correspond
      with previous reports of carbon monoxide neurotoxic effects in patients with
      moderate carbon monoxide poisoning. Low-level exposure to carbon monoxide results
      in impairment of higher cognitive functions. Neuropsychological testing appears
      to be sensitive in the detection of subtle neurologic dysfunctions resulting from
      carbon monoxide poisoning.

PMID- 9626777
TI  - Magnetic resonance spectroscopy: use in monitoring MELAS treatment.
AB  - BACKGROUND: Sodium dichloroacetate has been used to treat patients with
      mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes
      (MELAS). Magnetic resonance spectroscopy (MRS) has been used to assess cerebral
      metabolism in MELAS, but to our knowledge, the findings of serial MRS studies
      performed after therapeutic intervention of strokelike episodes have not been
      reported. METHODS: Proton MRS was serially used to measure brain metabolites in
      strokelike regions and in clinically uninvolved brain regions in a patient with
      MELAS. PATIENT: A patient with MELAS and a strokelike episode clinically improved
      after treatment with sodium dichloroacetate. An elevated lactate-creatine ratio
      in the "stroke" region decreased on MRS studies after treatment. After a second
      episode, the lactate-creatine ratio increased from baseline in a region of the
      brain that was normal on magnetic resonance imaging scans. CONCLUSIONS: To our
      knowledge, this is the first study to assess the response to treatment of a MELAS
      strokelike episode and the first to show an increase in the lactate-creatine
      ratio in a brain region that was associated with a clinical abnormality, even
      though it appeared normal on magnetic resonance imaging. We conclude that MRS may
      help to monitor therapeutic efficacy in mitochondrial encephalomyopathies.

PMID- 9626778
TI  - Familial idiopathic intracranial hypertension with spinal and radicular pain.
AB  - OBJECTIVE: To describe a mother and her 2 sons affected by idiopathic
      intracranial hypertension (IIH), associated in the sons with root irritation
      symptom. Unlike the other 4 families reported previously, obesity was not present
      in our patients. DESIGN: Case reports. SETTING: Department of pediatrics in a
      university school of Medicine, Naples, Italy. PATIENTS: A mother (aged 36 years)
      and her 2 sons (aged 14 and 9 years) developed IIH at different times.
      Neuroimaging showed an empty sella in the mother, while IIH was associated with
      spinal and radicular pain in her 2 sons. The mother and the younger son developed
      permanent visual loss. CONCLUSIONS: Ophthalmologic follow-up in our patients
      indicates that IIH is a chronic disease. Surgical treatment should be considered
      an option.

PMID- 9626779
TI  - Patients with epilepsy who die suddenly have cardiac disease.
AB  - BACKGROUND: Approximately 1 in 1000 patients with epilepsy dies suddenly and
      unexpectedly with no obvious medical cause. The purpose of this study was to
      determine if the hearts of such individuals harbor occult cardiac pathology.
      DESIGN: Following a comprehensive protocol, we performed careful pathologic
      evaluations of the hearts of 7 patients with epilepsy who died suddenly and 13
      previously healthy people who died by hanging or a drug overdose. Hearts were
      studied only when there was no history or gross anatomical evidence of heart
      disease or the use of adrenergic drugs. METHODS: Multiple sections of each heart
      were evaluated independently by 2 cardiac pathologists who were blinded to
      patient group. RESULTS: Pathologic conditions were found in 5 hearts in the group
      with epilepsy and in none of the hearts in the comparison group. Four of the 7
      hearts in the group with epilepsy had evidence of irreversible pathology in the
      form of perivascular and interstitial fibrosis. These 4 hearts plus a fifth had
      evidence of reversible pathology in the form of myocyte vacuolization. Lesions
      occurred predominantly in the subendocardium. CONCLUSION: Our results support the
      hypothesis that patients with epilepsy who die suddenly and unexpectedly have
      cardiac pathologic conditions that may be responsible for their deaths.

PMID- 9626780
TI  - Disc edema and retinal periphlebitis as the initial manifestation of sarcoidosis.

PMID- 9626781
TI  - Neurology was there in 1848.

PMID- 9626782
TI  - The central visual field in homonymous hemianopia: foveal or macular
      representation?

PMID- 9626783
TI  - Hemisphere-specific cognitive and motor changes after unilateral posteroventral
      pallidotomy.

PMID- 9626784
TI  - Management of carcinoma of the bladder.
AB  - Carcinoma of the bladder (CaB) is a common tumor of the genitourinary tract. In
      the United States in 1997, CaB was second in frequency of occurrence and third in
      mortality among genitourinary tumors. This tumor has a well-documented history of
      environmental and industrial causative factors. The strongest etiologic risk
      factors include the use of tobacco, which is thought to be responsible for half
      of the CaB diagnosed in men in the United States, and some arylamines. In the
      past 30 years, there has been major improvement in the survival of patients with
      this disease. Multiple factors were responsible for this accomplishment and they
      include: 1) better understanding of the natural history of CaB, 2) development of
      immunohistochemical analysis helpful in defining prognostic factors, 3) improved
      imaging and nonimaging diagnostic modalities helpful in making earlier diagnosis
      and better defining the true anatomical extent of the tumor, 4) development of
      more effective therapy for carcinoma in situ, 5) major improvement in surgical
      techniques resulting in better treatment outcomes, and 6) the wide use of
      adjuvant chemotherapy. Major stress has been placed on the quality of life of
      patients treated for CaB. Quality of life was improved by optimizing surgical,
      radiation, and medical treatment techniques. The two most important factors
      producing this quality-of-life improvement include: 1) the use of organ
      preserving therapy in properly selected patients that involves the use of a
      multimodality therapeutic approach with transurethral resection, radiation
      therapy, and chemotherapy; and 2) the ability to treat selected men and women
      with radical cystectomy followed by orthotopic reconstruction that allows
      patients nearly physiologic voiding. Current research efforts are directed toward
      better patient selection for appropriate therapy which is expected to increase
      patient survival and improve quality of life. Of particular importance in the
      selection of this optimal therapy in patients with CaB is a wide application in
      the clinical practice of important recent advances in molecular genetics.

PMID- 9626785
TI  - Fluorescence detection of flat transitional cell carcinoma after intravesical
      instillation of aminolevulinic acid.
AB  - Carcinoma in situ (CIS) of the bladder is a confounding disease that is difficult
      to recognize endoscopically because it is a flat cancer. Many studies have
      suggested its relationship with subsequent invasive disease. Early recognition of
      CIS therefore is essential in offering the patient the most appropriate treatment
      and the highest cure rate. Because white light cystoscopic examination is not
      sufficient to reveal areas of dysplasia or CIS, random biopsies are recommended.
      The authors evaluate whether amino levulinic acid (ALA) fluorescence detection
      could be helpful in diagnosing CIS and if the specificity could be enhanced by
      reducing the ALA dose. Sixteen patients with papillary bladder cancer, and CIS
      and dysplasia were given low-dose ALA. Fluorescence detection of the metabolized
      ALA was performed 3 hours later, with the naked eye, after blue light
      illumination. Carcinoma in situ or dysplasia was found in 50 biopsies. The
      sensitivity for detecting CIS was 94% with a specificity of 54%. Carcinoma in
      situ can be diagnosed with a very high accuracy through fluorescence detection
      after ALA instillation. Fluorescence detection can be achieved with the naked eye
      and does not necessitate either complex equipment or specially trained personnel.

PMID- 9626786
TI  - Salvage chemotherapy with paclitaxel, vinorelbine, and cisplatin (PVC) in
      anthracycline-resistant advanced breast cancer.
AB  - The tolerance and the efficacy of the paclitaxel-vinorelbine-cisplatin
      combination (PVC regimen) was evaluated in 33 patients with anthracycline
      resistant stage IV breast cancer, who had disease progression under anthracycline
      or mitoxantrone-based chemotherapy. Fourteen (42%) and 19 (58%) patients had
      primary and secondary resistance to anthracyclines, respectively; 70% had
      visceral metastases. Patients received vinorelbine (25 mg/m2) followed by
      paclitaxel (135 mg/m2) in a 3-hour infusion on day 1, and cisplatin (CDDP; 80
      mg/m2) on day 2, in a 3-week schedule. A total of 208 chemotherapy courses were
      administered (median six courses per patient). Grade 3/4 neutropenia occurred in
      13 patients (39%), seven of whom were hospitalized for neutropenic fever (5% of
      the courses). There was no toxic death. Grade 4 thrombocytopenia occurred in two
      patients (6%) and grade 3 anemia in three patients (9%). Grade 2 and 3
      neurosensory toxicity occurred in 11 patients (32%) and two patients (6%),
      respectively, and grade 3/4 fatigue was observed in four patients (12%). Two (6%)
      complete and 17 partial responses (52%) (total, 58%; 95% confidence interval, 42%
      75%) were documented. Stable disease was observed in eight patients (24%) and
      progression in six patients (18%). The median duration of response was 6.5+
      months. The median survival was 15+ months, and the 1-year survival was 67%. In
      conclusion, PVC regimen is an active and well-tolerated salvage chemotherapy in
      patients resistant to anthracycline.

PMID- 9626787
TI  - A prospective randomized study comparing high- and low-dose leucovorin combined
      with same-dose 5-fluorouracil in advanced colorectal cancer.
AB  - Although the efficacy of 5-fluorouracil (5-FU) modulated by leucovorin is well
      established for advanced colorectal cancer, the question of the most effective
      regimen and optimal dose of leucovorin remains unanswered. This prospective
      randomized trial compares low-dose (group 1) and high-dose (group 2) leucovorin,
      combined with the same dose of 5-FU to determine whether high-dose leucovorin was
      more beneficial than low-dose on overall survival. Inclusion criteria were:
      unresectable metastatic colorectal carcinoma, with or without evaluable tumor
      response; a performance status of less than grade 3 (World Health Organization
      classification); and no previous chemotherapy for metastases. Forty-two patients
      were randomized in group 1 (leucovorin, 20 mg/m2/day, days 1 through 5) and 41
      patients in group 2 (leucovorin, 200 mg/m2/day, days 1-5). All the patients in
      the two groups received a 1-hour infusion of 400 mg/m2/day 5-FU every 4 weeks.
      The two groups were matched with no statistically significant differences in
      gender ratio, site of primary tumor, performance status, and tumor extent.
      Toxicity in the two regimens was low and not significantly different between the
      two groups. Overall median survival was 346 days in group 1 and 323 days in group
      2 and was not significantly different between the two groups. At 1 year, the test
      of equivalence was significant (p < 0.01), demonstrating an absence of more than
      20% benefit in 1-year survival for the high-dose regimen. The use of high-dose
      leucovorin combined with 5-FU in the 5-day regimen does not significantly improve
      overall survival for patients who have metastatic colorectal cancer.

PMID- 9626788
TI  - Dacarbazine, fluorouracil, and leucovorin in patients with advanced
      neuroendocrine tumors: a phase II trial.
AB  - Chemotherapy of neuroendocrine tumors must be improved. The most widely used
      regimen, which combines streptozotocin with fluorouracil, commonly obtains poor
      results. The best response rate that has been reported for carcinoid tumors is
      33%. From July 1991 through September 1994, 18 patients who had advanced
      neuroendocrine tumors-including nine carcinoid tumors, seven neuroendocrine
      tumors of unknown primary site, one insulinoma, and one paraganglioma-were
      treated with a regimen of dacarbazine, 400 mg/m2/day, plus fluorouracil, 1
      g/m2/day, with leucovorin, 200 mg/m2/day, for 2 days every 21 days (DTIC-LVFU2
      protocol). The results were assessed according to the World Health Organization
      criteria of toxicity and response. Toxicity was moderate. The most severe side
      effects were grade 3 vomiting in two patients, grade 3 leukopenia in three
      patients, and grade 3 mucositis in one patient. The overall response rate was
      27%, with only one partial response for carcinoid tumors but one complete and
      three partial responses for the other tumor types. Efficacy was insufficient in
      patients who had carcinoid tumors but the combination of dacarbazine with
      fluorouracil and leucovorin could be an effective regimen for the treatment of
      neuroendocrine tumors of unknown primary site.

PMID- 9626789
TI  - Paclitaxel (Taxol) plus doxorubicin plus filgrastim in advanced sarcoma: a phase
      II study.
AB  - The authors evaluated the novel chemotherapeutic regimen of paclitaxel (Taxol,
      Bristol-Myers Squibb, Princeton, NJ, U.S.A.) plus doxorubicin plus filgrastim--a
      granulocyte colony-stimulating factor (G-CSF)--in advanced or metastatic sarcoma.
      Eligible patients must have had histologically confirmed advanced previously
      untreated soft-tissue sarcoma. All patients must have had bidimensionally
      measurable metastases. Treatment consisted of doxorubicin, 50 mg/m2 by
      intravenous push, followed 4 hours later by paclitaxel, 150 mg/m2 by continuous
      infusion over 24 hours every 3 weeks, plus G-CSF, 5 microg/kg, on days 3 through
      12 of each cycle. Cycles were repeated every 21 days. A one-time dose escalation
      for doxorubicin only (60 mg/m2) was allowed in all patients who experienced no
      significant toxicity after their first cycle of paclitaxel plus doxorubicin. From
      November 1993 through May 1996, 29 patients were entered in this study. Grade 3
      anemia occurred in three patients. Grade 3--4 neutropenia occurred in 20
      patients. Seven patients experienced at least one episode of neutropenic fever,
      including one death. Grade 3 thrombocytopenia occurred in four patients. There
      were six partial responses in 27 eligible patients, for a response rate of 22.2%
      (95% confidence interval, 7%-38%). Median time to progression was 4.5 months, and
      median overall survival was 10.2 months. The regimen of paclitaxel plus
      doxorubicin plus filgrastim as used in this study appears to have no more
      activity than single-agent doxorubicin.

PMID- 9626790
TI  - Carcinoid tumor regression with high-dose octreotide acetate: a patient report.
AB  - A patient who had carcinoid tumor of the ileum and liver and intraabdominal lymph
      node metastases sustained a substantial (more than 50%) reduction of metastatic
      tumor burden when treated with accelerated-dosage octreotide.

PMID- 9626791
TI  - A rare event of 5-fluorouracil-associated peripheral neuropathy: a report of two
      patients.
AB  - 5-Fluorouracil (5-FU) is known to cause multifocal cerebral demyelination, which
      is pathologically related to a central inflammatory demyelinating process. To
      date, no case of peripheral neuropathy has been described after the
      administration of 5-FU alone. The authors describe two patients who had
      peripheral neuropathy that developed while they were receiving 5-FU-based
      chemotherapy.

PMID- 9626792
TI  - Estrogen-receptor status of patients who underwent mastectomy for breast cancer
      with a disease-free interval of not less than 8 years.
AB  - The authors present a series of 1,226 patients who underwent total or partial
      mastectomy for breast cancer, who for a period of no less than 8 years from
      surgery did not have a relapse or relapsed only after 8 years. The patients were
      evaluated for estrogen-receptor (ER) content of the primary tumor. In the group
      of 237 patients who relapsed, only 8.8% (21 of 237) were ER negative; in the
      group of 989 patients without a relapse, 24.1% (239 of 989) were ER negative. The
      difference was significant (p < 0.001). Therefore, the absence of hormone
      receptors (ER negative) indicates a favorable prognosis after a period of 8
      years. For comparison, ER content in the group of patients who relapsed before 8
      years was evaluated; the results showed a different prognosis from the ER
      negative patients in this group. Because the behavior of ER-negative tumors in
      the cancer-affected breast is similar to that of non-hormone-dependent carcinomas
      arising in other parts of the body (which generally are considered cured after a
      long disease-free interval from surgery), we conclude that this repudiates the
      theory that confers to breast cancer the character of a systemic disease.

PMID- 9626793
TI  - Detection of trisomy 7 with fluorescence in situ hybridization and its
      correlation with DNA content and proliferating cell nuclear antigen-positivity in
      prostate cancer.
AB  - The authors applied fluorescence in situ hybridization (FISH), using specific DNA
      probes for chromosome 7, to routine paraffin-embedded tissue sections obtained
      from 35 radical-prostatectomy specimens. Proliferative activity was also
      evaluated using static cytometry to assess DNA content and immunohistochemistry
      for proliferating cell nuclear antigen (PCNA) positivity. These results were
      correlated with each other and with the morphologic parameters. The presence of
      three or more of chromosome 7 was observed in 71% of the cases, as was a high S
      phase, with a triploid prevalent DNA content and a PCNA index above mean value in
      66% of the cases. No correlation was detected between these findings and
      histologic grade; conversely, there was a significant correlation with stage (chi
      square = 5.33; p = 0.021). From these results, the authors maintain that the
      presence of an extra chromosome 7-correlated in most cases with an increase in
      cell kinetics and an advanced stage-may be an additional prognostic marker of
      aggressive behavior.

PMID- 9626794
TI  - Seromucoid fraction: a useful biomarker for patients with breast cancer.
AB  - Seromucoid fraction was measured in terms of mucoid proteins (MP) and hexose
      content from sera of 1) 47 healthy women, 2) 48 women who had benign breast
      diseases, 3) 151 untreated patients with breast cancer, and 4) 245 follow-up
      samples collected from the same breast cancer patients. Mucoid proteins and
      hexose levels were found to be significantly elevated in untreated patients with
      breast cancer when compared with the healthy participants (p < 0.001) and
      patients who had benign breast diseases (p < 0.02 and p < 0.05, respectively).
      Receiver operating characteristic (ROC) curve analysis revealed potential
      diagnostic application of both markers for breast cancer. A good correlation was
      observed between favorable treatment response and decline in serum-marker levels.
      The markers in patients who did not respond to anticancer therapy remained stable
      or increased during follow-up. These data indicate that seromucoid fraction can
      be an useful biochemical marker for breast cancer patients.

PMID- 9626795
TI  - Dose escalation study of carboplatin and cyclophosphamide with filgrastim
      support: a phase I study.
AB  - This clinical trial was designed to explore dose escalation of carboplatin and
      cyclophosphamide when supported with filgrastim. Twenty-seven patients who had
      advanced solid tumors received up to six cycles of treatment; a total of 92
      cycles of chemotherapy were delivered. Two control groups received standard-dose
      carboplatin (300 mg/m2) and cyclophosphamide (600 mg/m2), with and without
      filgrastim. Subsequently, the doses of both carboplatin and cyclophosphamide were
      increased simultaneously by 50% of the standard dose in sequential cohorts. Doses
      of up to 2.5 times the standard dose were explored. A final dose of carboplatin,
      600 mg/m2, and cyclophosphamide, 1,500 mg/m2, was tested in 4 patients. The
      duration of neutropenia was brief, even at the highest dose levels. The mean
      duration of grade 3 or 4 neutropenia was 5.8 days at standard dose without
      filgrastim and 5.4 days at 2.5 times standard dose with filgrastim. More severe
      neutropenia was more prolonged at higher doses but remained brief in duration.
      The mean duration of neutropenia of less than 100 x 10(6)/l was 0.4 days at
      standard dose without filgrastim and 1.3 days at 2.5 times standard dose. There
      was no evidence of cumulative neutropenia over repeated cycles of treatment. In
      contrast, thrombocytopenia was both dose limiting and cumulative. The mean
      duration of grade 3 or 4 thrombocytopenia was 1.6 days at standard dose and 9.6
      days at 2.5 times standard dose. An average of 2.3 platelet transfusions per
      cycle of treatment was required at the highest dose. Thrombocytopenia was worse
      with repetitive cycles of therapy. The mean duration of grade 3 or 4
      thrombocytopenia was 2.2 days after the first cycle of chemotherapy and 7.8 days
      after cycle four. The maximum tolerated dose, as defined prospectively, was not
      reached but further dose escalation was not thought to be warranted because of
      the severity of thrombocytopenia. When supported with filgrastim, carboplatin and
      cyclophosphamide can be administered safely with substantially increased dose and
      acceptable toxicity.

PMID- 9626796
TI  - Does a radiation dose-response relation exist concerning survival of patients who
      have soft-tissue sarcomas of the extremities? Radiation dose-response relation
      for soft-tissue sarcomas.
AB  - This study analyzes a single-institution experience by evaluating the impact on
      survival of increasing total dose of adjunctive irradiation in patients who had
      extremity soft-tissue sarcoma (ESTS). A retrospective review of the tumor
      registry at a university medical center from January 1984 through December 1992
      yielded a total of 59 surgical patients of ESTS. With follow-up ranging from 30
      to 135 months (median, 65 months), the 2-, 5-, and 8-year overall and disease
      free survival for all patients was 86%, 71%, 58% and 76%, 70%, 56%, respectively.
      Multivariate analyses using the Cox proportional hazards model revealed that
      total radiation dose (p = 0.02), American Joint Committee on Cancer stage (p =
      0.04), and tumor size (p = 0.006) were all significant prognostic factors of
      overall survival; however, only tumor size was predictive of disease-free
      survival (p = 0.02). When the effect of tumor size and disease stage were
      controlled in the Cox model, a dose-response curve between increasing total
      radiation dose and improved overall patient survival was indicated. This study
      demonstrates the significance of tumor size on predicting both overall and
      disease-free survival in patients who have soft-tissue sarcomas of the extremity.
      It also suggests, however, that a radiation dose-response relation may exist for
      overall survival. Future investigations should consider evaluating the minimal
      total radiation dose needed to optimize patient survival after limb-sparing
      surgery.

PMID- 9626797
TI  - Advanced carcinoma of the pancreas: phase II study of combined chemotherapy, beta
      interferon, and retinoids.
AB  - Because of the poor response of pancreatic cancer to conventional therapy, the
      authors performed a phase II pilot study to evaluate whether beta-interferon and
      retinoids, added to active chemotherapeutic agents, could increase response rate
      and survival in a group of patients who had metastatic disease. Twenty-three
      chemotherapy-naive patients were treated as follows: epirubicin, 60 mg/m2, and
      mitomycin C, 10 mg/m2, intravenously on day 1; folinic acid, 200 mg/m2, and 5
      fluorouracil (5-FU), 370 mg/m2, intravenously for 5 consecutive days. beta
      Interferon, 1 x 10(6) IU/m2, subcutaneously three times a week, and retinol
      palmitate, 50,000 IU orally twice a day, were given between chemotherapy cycles.
      Patients having responses and disease stabilization were maintained with the same
      dose of beta-interferon and retinol palmitate. Treatment was given every 4 weeks
      for four courses or until onset of progression. A median of three courses of
      chemotherapy was delivered to each patient. All patients were evaluable. Eight
      patients responded (35%) and 8 (35%) had stable disease. Median time to
      progression and survival for all patients were, respectively, 6.1 months and 11
      months. Toxicity was severe: 60% of patients had hematologic toxicity, 40% had
      gastrointestinal toxicity, 13% had cardiac toxicity, and 1 patient had a
      hemolitic-uremic syndrome. The combination of chemotherapy, beta-interferon, and
      retinoids shows activity in metastatic pancreatic carcinoma. Toxicity was high
      but patients who had responses and disease stabilization had prolonged symptom
      palliation.

PMID- 9626798
TI  - Synergistic activity of oxaliplatin and 5-fluorouracil in patients with
      metastatic colorectal cancer with progressive disease while on or after 5
      fluorouracil.
AB  - From February 1995 through October 1996, 25 patients with metastatic colorectal
      cancer showing a clinical resistance to 5-fluorouracil (5-FU) entered this study.
      Thirteen received oxaliplatin alone and 12 received it in combination with 5-FU.
      Oxaliplatin was administered at 130 mg/m2 over a 2-hour infusion every 3 weeks,
      alone or added either to 5-FU as a continuous infusion at 200 mg/m2 to 300 mg/m2
      (six patients) or to a 5-FU bolus, 375 mg/m2, plus leucovorin, 100 mg/m2, daily
      for 5 days every 3 weeks (6 patients). Eighty-six of 98 administered cycles were
      evaluable for toxicity (47 for oxaliplatin plus 5-FU and 39 for oxaliplatin
      alone). Hematologic toxicity was mild, occurring as grade 2 leukopenia in 23% of
      the cycles of 5-FU and oxaliplatin and in 5% of the cycles of oxaliplatin alone.
      The most common toxicity was neurologic (grade 1 to 2 in 60%-6% of the cycles of
      the combination, respectively, and 68%-10% of oxaliplatin given alone) as hand
      foot paresthesia or hypersensitivity to cold. No grade 4 toxicity was reported
      and only three patients in the 5-FU group developed grade 3 diarrhea. Grade 2
      nausea and vomiting occurred in 33% of the cycles when both drugs were given and
      in 15% when oxaliplatin was administered alone. The combination of oxaliplatin
      and 5-FU induced four partial remissions (33%; 95% confidence interval, 6%-60%),
      whereas eight patients of the whole group had stable disease. No response
      occurred when oxaliplatin was administered as a single agent. The results of this
      study confirm the antitumor activity of oxaliplatin when added to 5-FU in
      patients who have metastatic colorectal cancer previously refractory to 5-FU. The
      possible therapeutic synergy with 5-FU was not accompanied by increased toxicity.

PMID- 9626799
TI  - The usefulness of carcinoembryonic antigen testing in the overall management of
      patients with non-small-cell lung cancer.
AB  - Carcinoembryonic antigen (CEA) testing is a valuable adjunct in the overall
      management of patients who have non-small-cell lung cancer, especially when
      selecting surgical candidates for curative lung resection and in cases where the
      diagnosis is in doubt. Carcinoembryonic antigen levels above 50 strongly suggest
      advanced-stage cancer and should discourage lung resections in otherwise suitable
      cases. Carcinoembryonic antigen testing can enhance problem solving in difficult
      cases and help prevent needless invasive interventions.

PMID- 9626801
TI  - Monoclonal antibodies in the treatment of metastatic carcinoma to the liver:
      updated report of a pilot study including leukapheresis.
AB  - Twenty-two patients who had failed conventional treatment for advanced colorectal
      carcinoma metastatic to the liver were entered in this study. Survival from the
      date the hepatic disease was documented and ranged from 3 to 62 months, with an
      average of 20 months. Notably, 8 of the 22, or 36%, lived 24 months or more. Four
      patients, or 18%, survived 3 to 5 years after diagnosis of hepatic metastasis.

PMID- 9626800
TI  - Vinblastine, ifosfamide, gallium nitrate, and filgrastim in platinum- and
      paclitaxel-resistant ovarian cancer: a phase II study.
AB  - The authors performed a phase II trial of the VIG regimen (vinblastine,
      ifosfamide, and gallium nitrate) in patients who had advanced ovarian cancer who
      were refractory to cisplatin and/or carboplatin and whose disease had progressed
      after paclitaxel-based therapy. This was a heavily pretreated population, with
      five patients having received two to three prior chemotherapy regimens and six
      patients having received more than six prior chemotherapy regimens, with an
      average of 21 therapy cycles per patient. Fourteen patients were treated with
      vinblastine, 0.08 mg/kg intravenously on days 1 and 2; ifosfamide, 900 mg/m2
      intravenously on days 1 through 5 with standard mesna uroprotection; and gallium
      nitrate administered as a continuous intravenous infusion at 225 mg/m2 per 24
      hours x 120 hours. Granulocyte colony-stimulating factor (G-CSF) was administered
      subcutaneously at 5 microg/kg/day beginning on day 7 until day 13. Five of 14
      patients achieved a partial response for an overall response rate of 36% (95%
      confidence interval, 14%-68%). The median response duration was 14 weeks.
      Toxicity was primarily hematologic, with anemia and leukopenia being most
      significant. There were no treatment-related deaths. Further evaluation of this
      regimen in a less heavily pretreated population is warranted.

PMID- 9626802
TI  - CODE (cisplatin, vincristine, doxorubicin, etoposide) plus granulocyte colony
      stimulating factor in advanced non-small-cell lung cancer: a Hoosier Oncology
      Group phase II trial.
AB  - This phase II trial investigated the activity and toxicity of CODE (cisplatin,
      vincristine, doxorubicin, etoposide) chemotherapy with the addition of
      granulocyte colony-stimulating factor (G-CSF) in patients who had chemotherapy
      naive, advanced, or metastatic non-small-cell lung cancer. Treatment consisted of
      cisplatin, 25 mg/m2, administered weeks 1 through 9; vincristine, 1 mg/m2, weeks
      1, 2, 4, 6, and 8; doxorubicin, 40 mg/m2, weeks 1, 3, 5, 7, and 9; and etoposide,
      80 mg/m2 intravenously day 1 and 160 mg/m2 orally, days 2 and 3 on weeks 1, 3, 5,
      7, and 9. Granulocyte colony-stimulating factor, 5 microg/kg, was administered
      subcutaneously on all days that patients were not receiving chemotherapy. From
      April 1992 through April 1993, 42 patients were entered on study. The principal
      toxicities were hematologic. Grade 3-4 anemia was seen in 21 patients. Grade 3-4
      thrombocytopenia was seen in 9 patients. Grade 3-4 neutropenia occurred in 29
      patients. Eight patients experienced a neutropenic febrile episode requiring
      antibiotics. Nonhematologic toxicities included weight loss and fatigue.
      Responses were seen in 10 of 42 patients, for an overall response rate of 24%
      (95% confidence interval, 12%-39%) and a median survival of 7.1 months. The CODE
      chemotherapy regimen has activity similar to other previously described cisplatin
      based regimens, with a significant amount of both hematologic and nonhematologic
      toxicity. Its continued use in patients who have previously untreated non-small
      cell lung cancer cannot be recommended, based on the results of this study.

PMID- 9626803
TI  - The role of radiotherapy in the management of carcinoma in situ of the glottic
      larynx.
AB  - Carcinoma in situ of the glottic larynx is a rare malignancy, comprising only 1%
      to 2% of laryngeal biopsy. The management of these lesions remains controversial.
      In this article, the authors present results and analysis of the management of 20
      patients having these lesions treated by radiotherapy. A total of 20 patients who
      had carcinoma in situ of the glottis were treated with curative intent with
      radiotherapy at the Veterans Administration Medical Center, Minneapolis,
      Minnesota, U.S.A. from November 1972 through March 1993. Before radiotherapy,
      eight patients had only biopsies of the glottic larynx, five had one stripping
      procedure, and seven patients had two or three stripping procedures. Of the 20
      patients, 19 are available for retrospective analysis, with a minimum follow-up
      of 4 years and a median follow-up of 7.3 years. Treatment was given to all
      patients by megavoltage units (cobalt 60, 2; 4-mV linear accelerator, 18).
      Patients were treated using bilateral opposed wedged 6-cm x 6-cm fields, with a
      dose of 1.75 Gy per fraction to a total median dose of 68.4 Gy in 40 fractions
      over 56 elapsed treatment days. The Kaplan-Meier method was used for survival
      analysis. The 4-year disease-free survival was 95% after irradiation. The
      actuarial disease-free survival for 5 and 10 years was 95%. Surgical salvage
      failed in one patient who had a laryngectomy for recurrent invasive squamous cell
      carcinoma at 34 months after radiotherapy. Two patients developed severe
      shortness of breath because of laryngeal edema, which required tracheostomy.
      Sixteen patients reported subjective significant improvement of their voice
      quality, and four reported no change. Radiotherapy is an excellent choice for
      patients who have recurrent carcinoma in situ after undergoing stripping
      procedures or for those patients who live too far from a medical facility to
      allow close follow-up and repetitive surgical procedures. These results are
      comparable to those of other investigators who used radiotherapy with higher dose
      per fraction.

PMID- 9626804
TI  - Curative radiotherapy for stage II-III squamous cell carcinoma of the glottic
      larynx.
AB  - The authors report the analysis and outcome of curative radiotherapy for stage II
      and III squamous cell carcinoma of the glottic larynx. Thirty-nine men with
      invasive, previously untreated squamous cell carcinoma of the glottic larynx were
      referred for curative radiotherapy from May 1976 through June 1991, to the
      Veterans Administration Medical Center in Minneapolis, Minnesota, U.S.A. Thirty
      eight patients had T2N0 disease, and one had T2N1 disease. All patients were
      treated by megavoltage units (two by cobalt 60 and 37 by 4 mV-linear
      accelerator). The median fractional dose was 1.80 Gy, and the median total tumor
      dose was 70.20 Gy. Surgical salvage was reserved for irradiation failure. All
      patients had a minimum 5-year follow-up. The Kaplan-Meier method was used for
      survival analysis. The 5-year disease-free survival with voice preservation after
      radiotherapy was 70.2% (80% for T2a and 64% for T2b patients). The ultimate 5
      year disease-free survival for all T2 patients after surgical salvage was 91%. In
      nine patients, ten second primary malignancies were diagnosed during follow-up.
      Nine of these second lesions occurred in the aerodigestive tract. Curative
      radiotherapy using conventional fractionation regimen with surgical salvage for
      irradiation failure is an efficacious modality for T2N0 and T2N1 squamous cell
      carcinoma of the glottic larynx. A high incidence of second malignancy was noted
      in our series.

PMID- 9626805
TI  - A phase II trial of amonafide in patients with mixed mesodermal tumors of the
      uterus: a Gynecologic Oncology Group study.
AB  - Amonafide demonstrated a poor response rate and substantial toxicity in patients
      who had measurable, advanced mixed mesodermal tumors of the uterus. Amonafide-a
      drug that acts through intercalation of tumor DNA-was used to treat 16 patients
      who had measurable, advanced mixed mesodermal tumors of the uterus as part of a
      Gynecologic Oncology Group (GOG) Phase II study. The starting dose was 300 mg/m2
      intravenously over 1 hour for 5 consecutive days every 3 weeks. Severe or life
      threatening hematologic toxicity occurred in 50% of the patients. Two patients
      experienced vomiting requiring hospitalization. Other toxicities were not severe.
      One patient had a partial response and one had stable disease, each lasting 4
      months. This dose schedule was associated with poor response rate and substantial
      toxicity.

PMID- 9626806
TI  - Comparison of neutrophil and monocyte function by microbicidal cell-kill assay in
      patients with cancer receiving granulocyte colony-stimulating factor, granulocyte
      macrophage colony-stimulating factor, or no cytokine after cytotoxic
      chemotherapy: a phase II trial.
AB  - Functional effects of recombinant human granulocyte colony-stimulating factor
      (rhG-CSF) and recombinant human granulocyte-macrophage colony-stimulating factor
      (rhGM-CSF) were prospectively measured by harvesting blood samples from 51
      oncology patients (21 who were receiving no cytokines, 14 receiving rhGM-CSF, and
      16 who were receiving rhG-CSF) just before cytotoxic chemotherapy (baseline)
      immediately before the last cytokine dose (pre), 2 hours after the last cytokine
      dose (post), and 48 hours after the pre period (follow-up). Neutrophils and
      monocytes were separated and functional effects were measured by comparing cell
      kill percentages, as determined by a microbial cell-kill assay against
      Staphylococcus aureus and Candida albicans. Optimal cell concentrations (2 x
      10(6) monocytes/ml; 4 x 10(6) neutrophils/ml) and effector-to-cell ratios (1:50)
      were initially determined with blood samples harvested from 23 healthy
      volunteers. Results in oncology patients indicated that rhGM-CSF improved
      monocyte-killing activity against S. aureus at follow-up, compared with controls
      (p = 0.0094) and compared with monocytes from rhG-CSF-treated patients at the
      post period (p = 0.014). Cell-killing percentage of the rhGM-CSF-treated patients
      was also enhanced against C. albicans during the post period, compared with
      controls (p = 0.011) and rhG-CSF-treated patients (p = 0.067). Neutrophil
      activity was not altered by either cytokine. In conclusion, monocyte-induced
      microbial killing was enhanced in oncology patients receiving rhGM-CSF after
      cytotoxic chemotherapy, compared with patients receiving rhG-CSF or no cytokines.
      No differences in neutrophil activity were observed between patients receiving
      either cytokine.

PMID- 9626807
TI  - 5-Fluorouracil dose intensification and granulocyte-macrophage colony-stimulating
      factor in cisplatin-based chemotherapy for relapsed squamous cell carcinoma of
      the head and neck: a phase II study.
AB  - A previous phase I study showed that in a 5-day combination of cisplatin (CDDP)
      20 mg/m2/day and 5-fluorouracil (5-FU) intravenous bolus, the maximum tolerable
      dose of 5-FU is 200 mg/m2/day without the use of growth factors and 300 mg/m2/day
      with recombinant human granulocyte-monocyte colony-stimulating factor (rhGM-CSF)
      support. In the present phase II study, 26 patients with relapsed and/or
      metastatic squamous cell carcinoma of the head and neck (SCCHN) were treated with
      CDDP, 20 mg/m2/day, and 5-FU, 300 mg/m2/day intravenous bolus, for 5 consecutive
      days every 3 weeks. Granulocyte-macrophage colony-stimulating factor, 5 mg/kg/day
      subcutaneously, was administered from days 8 to 19. All patients had previously
      undergone surgery and/or radiation treatment. None had previously received
      chemotherapy. Mucositis (19% of the patients) and thrombocytopenia (42%) were the
      most frequent, but generally mild, toxicities. Relevant, GM-CSF-related side
      effects were detected in 12% of the patients. The median number of cycles
      delivered was four. Three complete and five partial responses were recorded (31%
      overall response rate). Further investigation of this regimen is unwarranted
      because of both its lack of improvement in antitumoral activity and the high
      costs incurred with the use of growth factors.

PMID- 9626808
TI  - Results of two consecutive trials of dose-intensive chemotherapy with doxorubicin
      and ifosfamide in patients with sarcomas.
AB  - The authors evaluate the efficacy and feasibility of dose-intensive doxorubicin
      and ifosfamide combination chemotherapy in patients with sarcomas. From January
      1995 to April 1996, 33 evaluable patients with either metastatic sarcoma or
      primary sarcomas with a high-risk for metastases (all except one was previously
      untreated with chemotherapy) were treated on two consecutive protocols. The
      median age was 45 years (range, 15-68 years). The first protocol included
      doxorubicin at 75 mg/m2 given as a 72-hour infusion on days 1 to 3 along with
      ifosfamide at 2 g/m2/d over 2 hours x 5, days 1 to 5 (protocol AI 75/10).
      Granulocyte colony-stimulating factor (G-CSF) was used only if indicated
      according to American Society of Clinical Oncology guidelines. The second
      protocol included doxorubicin at 90 mg/m2 as a 72-hour continuous infusion and
      ifosfamide at 2.5 g/m2/d for 4 days (protocol AI 90/10) with prophylactic G-CSF.
      A median of four cycles were administered (range, 1-6). Three patients achieved a
      pathologic complete response (CR) and 18 patients achieved a partial response
      (PR) for a response rate (RR) of 64% (95% confidence interval (CI), 45-80%).
      Response rate for the subset of patients with soft-tissue sarcomas was 66% (95%
      CI, 46-82%). Only three patients progressed on therapy. Febrile neutropenia was
      noted in 31% of cycles at AI 75/10 and in 56% of cycles at AI 90/10. One patient
      developed reversible grade 3 central nervous system (CNS) toxicity. There was one
      treatment-related death on AI 90/10 secondary to doxorubicin cardiac toxicity at
      a cumulative dose of 435 mg/m2. Dose-intensive doxorubicin plus ifosfamide is
      feasible in appropriately selected patients and appears to be a very active
      regimen in patients with sarcomas. The authors are currently testing this regimen
      with G-CSF and thrombopoietin.

PMID- 9626809
TI  - Melanoma x macrophage hybrids with enhanced metastatic potential.
AB  - Studies were conducted on the hypothesis that melanoma metastasis might be
      initiated through the generation of hybrids comprised of cells of the primary
      tumor and tumor-infiltrating leukocytes. Fusion hybrids were generated in vitro
      between weakly metastatic Cloudman S91 mouse melanoma cells and normal mouse or
      human macrophages. Hybrids were implanted s.c. in the tail and mice were
      monitored for metastases. Controls included parental S91 cells, autologous S91 x
      S91 hybrids, and B16F10 melanoma cells. Of 35 hybrids tested, most were more
      aggressive than the parental melanoma cells, producing metastases sooner and in
      more mice. A striking characteristic was heterogeneity amongst hybrids, with some
      lines producing no metastases and others producing metastases in up to 80% of
      mice. With few exceptions, hybrids with the highest metastatic potential also had
      the highest basal melanin content whereas those with the lowest metastatic
      potential were basally amelanotic, as were the parental melanoma cells. A
      spontaneous in vivo supermelanotic hybrid between an S91 tumor cell and DBA/2J
      host cell was one of the most metastatic lines. Hybrids with the highest
      metastatic potential also exhibited markedly higher chemotaxis to fibroblast
      conditioned media. Histologically, the metastatic hybrids demonstrated vascular
      invasion and spread to distant organs similar to that of metastatic melanomas in
      mice and humans. Thus previous findings of enhanced metastasis in leukocyte x
      lymphoma hybrids can now be extended to include leukocyte x melanoma hybrids.
      Whether such hybridization is a natural cause of metastasis in vivo remains to be
      determined; however the fusion hybrids with genetically-matched parents described
      herein so closely resembled naturally-occurring metastatic melanoma cells that
      they could serve as useful new models for studies of this complex and deadly
      phenomenon.

PMID- 9626810
TI  - Relation of matrilysin messenger RNA expression with invasive activity in human
      gastric cancer.
AB  - Matrilysin is a member of the matrix metalloproteinase gene family which is
      believed to play an important role in tumor progression. Expression of matrilysin
      mRNA was examined by reverse transcription-polymerase chain reaction combined
      with Southern blot analysis in 46 human primary gastric cancers. Overexpression
      of matrilysin was observed in 28 (61%) of gastric cancer tissues. The positive
      expression ratio of matrilysin was significantly higher in the gastric cancers of
      subserosa or beyond it than in those within the submucosal layer.
      Immunohistochemical study with anti-matrilysin monoclonal antibody revealed that
      matrilysin was mainly expressed on cancer cells but not or very weakly expressed
      on other cells. In addition, an activated form of matrilysin detected by
      zymographic analysis was observed in gastric cancer tissues whereas none was
      detected in non-cancerous tissues, suggesting that matrilysin may directly and
      powerfully contribute to the invasion step of human gastric cancer. In order to
      gain more insight into the relationship of this metalloproteinase to invasive
      activity, we also modulated the expression of matrilysin in gastric cancer cells
      by DNA transfection using gastric cancer cell lines. Overexpression of matrilysin
      rendered the gastric cancer cells more invasive in vitro. Concomitant with
      clinical investigations, matrilysin may be an important metalloproteinase in the
      progression of gastric cancer.

PMID- 9626812
TI  - Alendronate blocks TGF-beta1 stimulated collagen 1 degradation by human prostate
      PC-3 ML cells.
AB  - We have previously shown that alendronate can prevent human PC-3 ML tumor cell
      metastasis to the bone (Wang and Stearns, 1991, Differentiation, 48, 115-25). In
      this paper, ELISAs and Western blots showed that TGF-beta1 stimulated the
      secretion of a 72 kDa matrix metalloproteinase 2 (MMP-2) to enhance the
      solubilization of radiolabeled collagen 1 by metastatic human prostate PC-3 ML
      cells. A potent bisphosphonate compound, alendronate, inhibited MMP-2 secretion
      to block solubilization of collagen 1. Alendronate failed to inhibit MMP-2
      activity directly, but instead appeared to block cellular secretion of MMP-2.
      Alendronate failed to inhibit secretion of tissue inhibitor of metalloproteinase
      2 (TIMP-2; the inhibitor of MMP-2) and the decrease in collagen 1 solubilization
      observed may occur, in part, from changes in the molar stoichiometry of TIMP-2 to
      MMP-2. We conclude that alendronate may be a potent inhibitor of bone resorption
      based on its ability to block MMP-2 secretion by tumor cells.

PMID- 9626811
TI  - TAC-101, a benzoic acid derivative, inhibits liver metastasis of human
      gastrointestinal cancer and prolongs the life-span.
AB  - We examined the anti-tumor effect of a novel benzoic acid derivative, TAC-101 (4
      [3,5-bis(trimethylsilyl) benzamide] benzoic acid) on models with liver
      metastasis. Oral administration of TAC-101 significantly inhibited spontaneous
      liver metastasis of AZ-521 (human gastric cancer ) by orthotopic implantation to
      athymic nude mice. It also inhibited both the liver metastasis of AZ-521 induced
      by intrasplenic injection and the secondary lung metastasis from the liver. In
      addition, TAC-101 inhibited the proliferation of Co-3 (human colon
      adenocarcinoma) that formed a single nodule in the liver of athymic nude mice by
      intrahepatic implantation. The growth inhibitory effect of TAC-101 on AZ-521
      experimental liver metastasis was observed when treatment was started on day 7,
      14, or 21 which may correspond to the progressive stage of liver metastasis in
      clinical settings. Multiple administration of TAC-101 (8 mg/kg/day) significantly
      prolonged survival time of the animals with liver metastasis by intrasplenic
      injection of AZ-521 (T/C = 230%) and A549 (human lung adenocarcinoma; T/C =
      186%). These effects of TAC-101 were stronger than those of 5-FU, CDDP or ATRA.
      Furthermore, TAC-101 inhibited the binding of AP-1 to DNA on electrophoretic
      mobility shift assay using nuclear extract of AZ-521 cells, although ATRA did not
      inhibit. These findings suggested that TAC-101 may be a candidate for a new class
      of anti-cancer agents for liver metastasis.

PMID- 9626813
TI  - A unique allogenic model of metastatic pheochromocytoma: PC12 rat
      pheochromocytoma xenografts to nude mice and establishment of metastases-derived
      PC12 variants.
AB  - Local invasion and metastatic spread to distant sites are major causes of death
      in patients with malignant pheochromocytoma. Since appropriate in vivo models do
      not exist, little is known about the underlying mechanisms of tumor growth and
      invasion. We, therefore, developed an animal model of malignant pheochromocytoma
      and established organotropic metastatic variants of PC12 rat pheochromocytoma
      cells. PC12 cells were established as xenografts to BALB/c NCR-NU mice.
      Subsequent to development of tumors or metastases, primary cultures from local
      tumors, metastases to lymph nodes, lungs and liver were established. These were
      subcultured in vitro and reinjected for up to five successive in vivo/in vitro
      cycles. Xenografted PC12 cells grew tumors with a doubling time of 6.78 +/- 0.58
      days during log phase of tumor growth, killing hosts within 5-12 weeks depending
      on the experimental conditions. Tumors reproducibly metastasized to lymph nodes
      and the lung. Spontaneous metastases to the liver were not observed, but were
      achieved by intrasplenic injection of parent PC12 cells. In vitro, the metastatic
      cell lines displayed striking differences in morphology, overall growth patterns
      and nutritional requirements as well as binding to purified extracellular matrix
      proteins compared to the parent cell line. In vivo, the metastatic variants
      showed marked enhancement of metastatic ability. This is the first report of PC12
      rat pheochromocytoma cells to exhibit the malignant phenotype in vivo. We also
      established variant PC12 cell lines that preferentially metastasized to specific
      sites and that had acquired different in vitro behavior and ability to
      metastasize. This unique model system should be useful for further studies
      relating to the invasion and metastases of pheochromocytoma and may prove
      valuable for investigations of novel antineoplastic therapies in vitro and in
      vivo.

PMID- 9626814
TI  - Time and dose dependency of the suppression of pulmonary metastases of rat
      mammary cancer by amiloride.
AB  - Amiloride is an inhibitor of urokinase plasminogen activator (uPA), an essential
      component of the plasminogen/plasmin enzyme system. Inhibition of uPA prevents
      the conversion of plasminogen to tumor cell surface bound plasmin which is
      required for initiation of the metastatic process. MATB rat mammary cancer cells
      were introduced into the jugular venous system of 80 Fisher 344 female rats.
      Amiloride at high and low dosages was administered in the drinking water at the
      time of, prior to or several days following the tumor cell inoculation and
      continued daily for 10 days post inoculation. Control rats were maintained on
      water alone. The middle lobe of the right lung was examined microscopically for
      numbers of metastases. Suppression of metastases was significant at high
      amiloride dosages in all groups, and at low dosage when administered prior to
      inoculation. We conclude that amiloride suppresses induced metastases of rat
      mammary cancer, the effect being dose- and time-dependent.

PMID- 9626815
TI  - Inhibition of VLA-4 and up-regulation of TIMP-1 expression in B16BL6 melanoma
      cells transfected with MHC class I genes.
AB  - The effect of MHC class I gene transfection on the metastatic properties of
      B16BL6 melanoma cells was investigated. BL6-8 melanoma cells transfected with H
      2Kb or H-2Kd, but not H-2Dd or H-2Ld, genes showed a dramatic reduction in their
      ability to generate experimental metastases in immunosuppressed CB6F1 mice. This
      observation suggested that some changes in the metastatic phenotype may have been
      induced in the H-2K- transfected melanoma cells. Analyses of adhesive and
      invasive properties of BL6-8 melanoma cells transfected with H-2 class I genes
      have been performed. We found that the loss of metastatic properties in the H-2Kb
      or H-2Kd gene-transfected melanoma cells was associated with reduced adherence to
      endothelial cells, laminin and collagen IV, decreased ability to form homotypic
      cell aggregates and with a complete loss of VLA-4 integrin expression. In
      addition, BL6-8 melanoma cells transfected with H-2K genes demonstrated reduced
      ability to invade Matrigel that paralleled up-regulation of TIMP-1 expression.
      Incubation of untransfected BL6-8 clone or B16F1 cells with 5-azacytidine
      similarly resulted in up-regulation of TIMP-1, suggesting that the changes in
      methylation of TIMP-1 gene could be responsible for TIMP-1 expression in the H-2K
      transfected BL6-8 melanoma cells. Transfection of BL6-8 cells with the H-2Dd/Ld
      genes did not affect their adhesive and invasive properties. Previously we
      reported that reduction in the metastatic properties of the H-2Kb transfected
      cells was associated with alterations in cell surface carbohydrates with
      appearance of alpha-galactosyl epitopes and reduction in cell surface
      sialylation. The present data indicate that, in addition to changes in cell
      surface carbohydrates, reduction in adhesive properties and up-regulation of TIMP
      1 may be responsible for the observed loss of metastatic potential of BL6-8 cells
      transfected with the H-2K genes.

PMID- 9626816
TI  - Pharmacological control of lung metastases of solid tumours by a novel ruthenium
      complex.
AB  - Imidazolium trans-imidazoledimethylsulphoxidetetrachlororuthenate ImH[trans
      RuCl4(DMSO)Im] (NAMI-A), a ruthenium compound that replaces Na+ with ImH+ in the
      molecule of Na[trans-RuCl4(DMSO)Im] (NAMI), was studied for the anti-metastasis
      effects in models of solid metastasizing tumours of the mouse. NAMI-A, given i.p.
      at 35 mg/kg/day for six consecutive days, a dose equimolar to that of NAMI, to
      mice bearing Lewis lung carcinoma and MCa mammary carcinoma, markedly reduces
      lung metastasis weight by 80-90%, with an effect equal or even superior to that
      of NAMI, depending on the experimental system adopted. Correspondingly, NAMI-A
      increases the content of connective tissue in the tumour matrix, around blood
      vessels, and in the tumour capsule, augments the percentage of tumour cells in
      G2/M phase and reduces the amount of CD45+ cells infiltrating the tumour
      parenchyma. The effects of the same doses on spleen lymphocytes correspond to an
      increase of CD8+ subset without any change of the distribution of cells in G0/G1,
      S and G2/M phases. The study shows that NAMI-A behaves similarly to NAMI on the
      several parameters examined in comparison experiments and therefore we suggest to
      credit NAMI-A with all the biological actions already described for NAMI during
      the last 3 years. The replacement of Na+ with ImH+ therefore, besides the better
      chemical stability of the molecule, confers to [trans-RuCl4(DMSO)Im]- a closer
      similarity with a true drug to be used in humans, and suggests this molecule for
      future studies of preclinical toxicology and phase I and II clinical trials.

PMID- 9626817
TI  - Adhesion polypeptides are useful for the prevention of peritoneal dissemination
      of gastric cancer.
AB  - We examined the effect of adhesion polypeptides on the adhesion and invasiveness
      of gastric cancer cell lines. We previously reported the establishment of an
      extensively peritoneal-seeding cell line, OCUM-2MD3, from a poorly seeding human
      scirrhous gastric carcinoma cell line, OCUM-2M. Both alpha2beta1 and alpha3beta1
      integrin expression was markedly increased on OCUM-2MD3 cells compared with OCUM
      2M cells, and the ability of OCUM-2MD3 cells to bind to the extracellular matrix
      (ECM) was also significantly higher than that of OCUM-2M cells. The adhesion
      polypeptides, YIGSR and RGD, and two RGD derivatives significantly inhibited the
      adhesion of OCUM-2MD3 cells to the submesothelial ECM, while not inhibiting the
      adhesiveness of OCUM-2M cells and two well differentiated human gastric cell
      lines, MKN-28 and MKN-74. The YIGSR and RGD peptides also significantly inhibited
      the invasiveness of OCUM-2MD3 cells. The survival of nude mice with peritoneal
      dissemination given YIGSR sequence intraperitoneally was obviously longer than
      that of untreated mice. The survival of mice treated with RGD was also improved,
      and this effect was increased using the RGD derivatives, poly(CEMA-RGDS) and CM
      chitin RGDS. These polypeptides appear to block the binding of integrins, which
      are expressed on OCUM-2MD3 cells, to the submesothelial ECM, and consequently
      inhibit peritoneal implantation. The peritoneal injection of adhesion
      polypeptides may be a new therapy against the dissemination of scirrhous gastric
      cancer, and may be useful for the prevention of dissemination in high-risk
      patients.

PMID- 9626818
TI  - Establishment of lymph node metastatic model for human gastric cancer in nude
      mice and analysis of factors associated with metastasis.
AB  - The actual mechanisms responsible for lymph node metastasis in gastric cancer are
      still unclear. To investigate the mechanisms of lymph node metastasis in gastric
      cancer, we established a lymph node metastatic model for human scirrhous gastric
      carcinoma. Lymph node metastasis had frequently developed after orthotopic
      implantation of OCUM-2M LN derived from a scirrhous gastric cancer cell line,
      OCUM-2M, which had low capacity for lymph node metastasis. We elucidated the
      different characteristics including binding ability, migratory capacity and
      immunoresponses induced by the cell surface molecules of these two cell lines.
      The binding ability to Matrigel and migratory capacity of OCUM-2M LN cells were
      significantly greater than those of OCUM-2M cells. On flow cytometric analysis,
      both OCUM-2M and OCUM-2M LN cells strongly expressed HLA-I (99.5 and 97.1%) and
      LFA-3 (76.6 and 99.2%) in level of expression between the two cell lines, but
      neither cell line expressed HLA-II (0.0 and 0.0%), B7-1 (0.0 and 0.0%) or B7-2
      (0.4 and 0.3%). ICAM-1 expression in OCUM-2M LN cells was weaker (0.7%) than that
      in OCUM-2M cells (36.8%). Strong adhesiveness and cytotoxicity of mononuclear
      lymphocytes for OCUM-2M cells were observed in adhesion and cytotoxic assays,
      both of which were significantly decreased by the addition of anti-ICAM-1
      antibodies. On the other hand, the adhesiveness and cytotoxicity of OCUM-2M LN
      cells were significantly less than those of OCUM-2M cells, and were not affected
      by the addition of anti-ICAM-1 antibodies. These findings suggest that decreased
      ICAM-1 expression in a new gastric cancer cell line with a high rate of lymph
      node metastasis may in turn decrease immune responses mediated through LFA-1
      dependent effector cell adhesion, and that this escape from the
      immunosurveillance system may be one of the factors inducing lymph node
      metastasis. In conclusion, we established a gastric cancer cell line, OCUM-2M LN,
      with a high rate of lymph node metastasis. An in vivo lymph node-metastatic model
      with this cell line should be useful for analysing the mechanism and therapeutic
      approach of lymph node metastasis.

PMID- 9626819
TI  - Heparin-induced thrombocytopenia.
AB  - Heparin-induced thrombocytopenia (HIT) is a potentially serious complication of
      heparin therapy and is being encountered more frequently in patients with
      cardiovascular disease as use of anticoagulant therapy becomes more widespread.
      Our understanding of the pathophysiology of this immune-mediated condition has
      improved in recent years, with heparin-platelet factor 4 complex as the culprit
      antigen in most patients. New sensitive laboratory assays for the pathogenic
      antibody are now available and should permit an earlier, more reliable diagnosis,
      but their optimal application remains to be defined. For patients in whom HIT is
      diagnosed, immediate discontinuation of heparin infusions and elimination of
      heparin from all flushes and ports are mandatory. Further management of patients
      with HIT is problematic at present, as there are no readily available alternative
      anticoagulant agents in the United States with proven efficacy in acute coronary
      disease. The direct thrombin inhibitors appear to be the most promising
      alternatives to heparin, when continued use of heparin is contraindicated, and
      the results of several multicenter trials evaluating their application in
      patients with HIT are awaited.

PMID- 9626820
TI  - C-reactive protein is a potent predictor of mortality independently of and in
      combination with troponin T in acute coronary syndromes: a TIMI 11A substudy.
      Thrombolysis in Myocardial Infarction.
AB  - OBJECTIVES: We evaluated C-reactive protein (CRP) alone and in conjunction with a
      rapid qualitative assay for cardiac-specific troponin T (cTnT) for predicting 14
      day mortality in patients with unstable angina or non-Q wave myocardial
      infarction (NQMI). BACKGROUND: Elevated CRP has been found to correlate with
      higher risk for cardiac events in patients with coronary disease. METHODS: At
      enrollment into the Thrombolysis in Myocardial Infarction (TIMI) 11A trial, a
      dose-ranging trial of enoxaparin for unstable angina and NQMI, serum was obtained
      for CRP measurement and rapid cTnT assay. RESULTS: Quantitative CRP and rapid
      cTnT assays were performed in all patients. CRP was higher among patients who
      died than in survivors (7.2 vs. 13 mg/dl, p = 0.0038). The probability of a
      positive rapid cTnT assay rose with increasing CRP concentration (p < 0.0001).
      Among patients with a negative rapid cTnT assay, the mortality rate was higher
      among patients with CRP > or = 1.55 mg/dl (5.80% vs. 0.36%, p = 0.006). Patients
      with both an early positive rapid cTnT assay (< or = 10 min until assay positive)
      and CRP > or = 1.55 mg/dl had the highest mortality, followed by those with
      either CRP > or = 1.55 mg/dl or an early positive rapid cTnT assay, whereas
      patients with both a negative rapid cTnT assay and CRP < 1.55 mg/dl were at very
      low risk (9.10% vs. 4.65% vs. 0.36%, p = 0.0003). CONCLUSIONS: Elevated CRP at
      presentation in patients with unstable angina or NQMI is correlated with
      increased 14-day mortality, even in patients with a negative rapid cTnT assay.
      Quantitative CRP and a rapid cTnT assay provide complementary information for
      stratifying patients with regard to mortality risk.

PMID- 9626821
TI  - Effects of reteplase and alteplase on platelet aggregation and major receptor
      expression during the first 24 hours of acute myocardial infarction treatment.
      GUSTO-III Investigators. Global Use of Strategies to Open Occluded Coronary
      Arteries.
AB  - OBJECTIVES: We sought to compare platelet characteristics after reteplase and
      alteplase therapy in the setting of the Global Use of Strategies to Open Occluded
      Coronary Arteries (GUSTO)-III trial. BACKGROUND: Platelet function may be
      impaired during thrombolysis in patients with an acute myocardial infarction. The
      effects of reteplase and alteplase on platelet aggregation and major surface
      antigen expression during the first 24 h of infarction therapy are unknown.
      METHODS: Platelet aggregation and receptor expression by flow cytometry were
      determined in 23 patients before thrombolysis and thereafter at 3, 6, 12 and 24
      h. RESULTS: Aggregation was higher after reteplase at 24 h when induced by 5
      micromol/liter adenosine diphosphate (ADP) (p = 0.007), 10 micromol/liter ADP (p
      = 0.02), collagen (p = 0.003) and thrombin (p = 0.009) than after alteplase.
      Reteplase therapy exhibited greater glycoprotein (GP) IIb/IIIa (p = 0.04), very
      late antigen-2 (p = 0.04) and platelet/endothelial cell adhesion molecule-I (p =
      0.002) expression at 24 h. Trends toward decreased receptor expression early (3
      to 6 h), followed by a progressive increase at 12 h and especially at 24 h
      occurred after both agents. CONCLUSIONS: In this prospective clinical ex vivo
      platelet study, similar patterns of platelet aggregation and surface receptor
      expression occurred during the first 24 h of coronary thrombolysis with reteplase
      and alteplase. However, after reteplase, indicators of platelet activity were
      higher at 24 h after thrombolysis than after alteplase. These data suggest that
      GP IIb/IIIa inhibitors or other antiplatelet strategies may be particularly
      advantageous when used 12 to 24 h after thrombolysis, especially after reteplase
      therapy. It is at this time point during the first day of coronary thrombolysis
      that GP IIb/IIIa is markedly expressed and platelets are most active.

PMID- 9626822
TI  - Influence of payor on use of invasive cardiac procedures and patient outcome
      after myocardial infarction in the United States. Participants in the National
      Registry of Myocardial Infarction.
AB  - OBJECTIVES: We sought to determine the influence of payor status on the use and
      appropriateness of cardiac procedures. BACKGROUND: The use of invasive procedures
      affects the cost of cardiovascular care and may be influenced by payor status.
      METHODS: We compared treatment and outcomes of myocardial infarction among four
      payor groups: fee for service (FFS), health maintenance organization (HMO),
      Medicaid and uninsured. Multivariate comparison was performed on the use of
      invasive cardiac procedures, length of hospital stay and in-hospital mortality in
      17,600 patients <65 years old enrolled in the National Registry of Myocardial
      Infarction from June 1994 to October 1995. To determine the appropriateness of
      coronary angiography, we compared its use in patients at low and high risk for
      cardiac events. RESULTS: Angiography was performed in 86% of FFS, 80% of HMO, 61%
      of Medicaid and 75% of uninsured patients. FFS patients were more likely to
      undergo angiography than HMO (odds ratio [OR] 1.27, 95% confidence interval [CI]
      1.13 to 1.42), Medicaid (OR 2.43, 95% CI 2.11 to 2.81) and uninsured patients (OR
      1.99, 95% CI 1.76 to 2.25). Similar patterns for the use of coronary
      revascularization were found. Among those at low risk, FFS patients were as
      likely to undergo angiography as HMO patients but more likely than Medicaid and
      uninsured patients. For those at high risk, FFS patients were more likely to
      undergo angiography than patients in other payor groups. Adjusted mean length of
      stay (7.3 days) was similar among all payor groups, but adjusted mortality was
      higher in the Medicaid group (Medicaid vs. FFS: OR 1.55, 95% CI 1.19 to 2.01).
      CONCLUSIONS: Payor status is associated with the use and appropriateness of
      invasive cardiac procedures but not length of hospital stay after myocardial
      infarction. The higher in-hospital mortality in the Medicaid cohort merits
      further study.

PMID- 9626823
TI  - Cost-effectiveness analysis of invasive and noninvasive tests in high risk
      patients treated with amiodarone after acute myocardial infarction.
AB  - OBJECTIVES: We sought to evaluate 1) the cost-effectiveness of amiodarone therapy
      in postinfarction patients; and 2) the influence of alternative diagnostic
      strategies (noninvasive only vs. noninvasive and electrophysiologic testing) on
      survival benefit and cost-effectiveness ratio of amiodarone therapy. BACKGROUND:
      The cost-effectiveness of amiodarone therapy in postinfarction patients is still
      unknown, and no study has determined which diagnostic strategy should be used to
      maximize amiodarone survival benefit while improving its cost-effectiveness
      ratio. METHODS: We designed a postinfarction scenario wherein heart rate
      variability analysis on 24-h Holter monitoring was used as a screening test for 2
      year amiodarone therapy in a cohort of survivors (mean age 57 years) of a recent
      myocardial infarction. Three different therapeutic strategies were compared: 1)
      no amiodarone; 2) amiodarone in patients with depressed heart rate variability;
      3) amiodarone in patients with depressed heart rate variability and a positive
      programmed ventricular stimulation. Total variable costs and quality-adjusted
      life expectancy during a 20-year period were predicted with use of a Markov
      simulation model. Costs and charges were calculated with reference to an Italian
      and American hospital. RESULTS: Amiodarone therapy in patients with depressed
      heart rate variability and a positive programmed ventricular stimulation was
      dominated by a blend of the two alternatives. Compared with the no-treatment
      strategy, the incremental cost-effectiveness ratio of amiodarone therapy in
      patients with depressed heart rate variability was $10,633 and $39,422 per gained
      quality-adjusted life-year using Italian costs and American charges,
      respectively. CONCLUSIONS: Compared with a noninterventional option, amiodarone
      prescription in all patients with depressed heart rate variability seems to be a
      more appropriate approach than the alternative based on the combined use of heart
      rate variability and electrophysiologic study.

PMID- 9626824
TI  - Cost-effectiveness of tests to assess the risk of sudden death after acute
      myocardial infarction.

PMID- 9626825
TI  - Randomized comparison of direct thrombin inhibition versus heparin in conjunction
      with fibrinolytic therapy for acute myocardial infarction: results from the GUSTO
      IIb Trial. Global Use of Strategies to Open Occluded Coronary Arteries in Acute
      Coronary Syndromes (GUSTO-IIb) Investigators.
AB  - OBJECTIVES: We sought to show that hirudin might interact differently with
      streptokinase (SK) and tissue-type plasminogen activator (t-PA), which could
      reduce the incidence of death or reinfarction at 30 days. BACKGROUND: In a large
      scale trial of patients with acute coronary syndromes, hirudin provided modest
      benefit compared with heparin. However, the interaction with thrombolytic agents
      was not specifically assessed. METHODS: Patients with symptoms of acute
      myocardial infarction and electrocardiographic ST segment elevation were treated
      with thrombolytic therapy and randomly assigned to receive hirudin or heparin.
      RESULTS: A total of 2,274 patients received t-PA, and 1,015 received SK. Baseline
      characteristics were balanced by antithrombin assignment. Among SK-treated
      patients, death or reinfarction at 30 days occurred more often in those treated
      with adjunctive heparin (14.4%) rather than hirudin (8.6%, odds ratio [OR] 1.78,
      95% confidence interval [CI] 1.20 to 2.66, p = 0.004). Among t-PA-treated
      patients, the rates were 10.9% with heparin and 10.3% with hirudin (OR 1.06, 95%
      CI 0.81 to 1.38, p = 0.68; for treatment heterogeneity: chi-square 4.20, degrees
      of freedom [df] 1, p = 0.04). After adjustment for baseline differences between
      thrombolytic groups, the rates were 9.1% for SK with hirudin, 10.3% for t-PA with
      hirudin, 10.5% for t-PA with heparin and 14.9% for SK with heparin (for treatment
      heterogeneity: chi-square 4.5, df 1, p = 0.03), suggesting that the beneficial
      treatment effect of hirudin was limited to the SK-treated patients. CONCLUSIONS:
      Hirudin interacts favorably with SK but not t-PA, highlighting the importance of
      thrombin activity after SK therapy and the potential for simulating the effects
      of a more potent fibrinolytic agent through direct antithrombin therapy.

PMID- 9626826
TI  - Early noninvasive identification of failed reperfusion after intravenous
      thrombolytic therapy in acute myocardial infarction.
AB  - OBJECTIVES: This study sought to evaluate a biochemical approach to the early
      noninvasive assessment of reperfusion. BACKGROUND: In patients with an acute
      myocardial infarction, a rapid noninvasive method of detecting failure of
      intravenous thrombolytic therapy to restore early Thrombolysis in Myocardial
      Infarction (TIMI) grade 3 flow in the infarct-related artery (IRA) is needed.
      METHODS: Serial blood samples were collected to assay creatine kinase-MB fraction
      (CKMB mass), cardiac troponin T and myoglobin concentrations in 105 patients with
      a myocardial infarction who underwent early angiography after intravenous
      streptokinase. The ratios of the 60- and 90-min concentrations to prethrombolytic
      values were used to determine an index that could identify failure to achieve
      TIMI grade 3 flow in the IRA at 90 min. RESULTS: Significant increases in serum
      concentrations of markers at 60 min were more likely with TIMI grade 3 flow (59
      patients) than with TIMI grade 0 to 2 flow (46 patients). Ratios < or = 5 at 60
      min after thrombolysis detected failure to achieve 90-min TIMI grade 3 flow with
      92% to 97% sensitivity, 43% to 60% specificity and 63% to 76% positive and 86% to
      94% negative predictive values. Ratios < or = 10 at 90 min showed 88% to 95%
      sensitivity, 49% to 65% specificity and 61% to 69% positive and 86% to 94%
      negative predictive values for TIMI flow grade < 3. The overall predictive values
      were thus similar for all three markers. CONCLUSIONS: In acute myocardial
      infarction treated with intravenous streptokinase, a simple measurement of
      increased serum concentrations of CKMB mass, cardiac troponin T or myoglobin at
      60 and 90 min can accurately predict failure to achieve TIMI grade 3 flow in the
      IRA at 90 min.

PMID- 9626827
TI  - Association of the missense Glu298Asp variant of the endothelial nitric oxide
      synthase gene with myocardial infarction.
AB  - OBJECTIVES: We examined the possible association between the missense Glu298Asp
      variant of the endothelial nitric oxide synthase (eNOS) gene and myocardial
      infarction (MI). BACKGROUND: Endothelium-derived nitric oxide (NO) plays a key
      role in the regulation of vascular tone. Recently, we reported that a missense
      Glu298Asp variant in exon 7 of the eNOS gene is a possible genetic factor
      involved in the pathogenesis of coronary spasm. Endothelium-derived NO also has
      vasoprotective effects by suppressing platelet aggregation, leukocyte adhesion
      and smooth muscle cell proliferation. METHODS: We screened 285 patients with an
      MI and 607 control subjects in Kumamoto Prefecture, Japan. Genotypes were
      determined by polymerase chain reaction-restriction fragment-length polymorphism
      analysis. RESULTS: The frequency of the missense Glu298Asp variant was
      significantly higher in the MI group than in the control group (21.1% vs. 13.3%,
      p = 0.003, odds ratio 1.73 for the dominant effect of the eNOS T allele).
      Multiple logistic regression analysis showed that the missense Glu298Asp variant
      was an independent risk factor for MI, as was diabetes mellitus, hypertension,
      cigarette smoking, hypercholesterolemia and body mass index. CONCLUSIONS: There
      was a significant association of the missense Glu298Asp variant of the eNOS gene
      with MI. This marker-disease association may be due to the impaired effects of NO
      on the cardiovascular system: dysregulation of vascular tone, platelet
      aggregation and leukocyte adhesion and smooth muscle cell proliferation, all of
      which promote coronary atherosclerosis and thrombosis.

PMID- 9626828
TI  - Rescue angioplasty after failed thrombolysis: technical and clinical outcomes in
      a large thrombolysis trial. GUSTO-1 Angiographic Investigators. Global
      Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded
      Coronary Arteries.
AB  - OBJECTIVES: We sought to assess the angiographic outcome, complication rates and
      clinical features of percutaneous transluminal coronary angioplasty (PTCA) after
      failed thrombolysis for acute myocardial infarction. BACKGROUND: "Rescue
      angioplasty" refers to mechanical reopening of an occluded infarct-related artery
      (IRA) after failed intravenous thrombolysis. Although the procedure is commonly
      performed, data describing its technical and clinical outcome are sparse. Early
      reports suggested that rescue PTCA is less often successful and produces more
      complications than primary PTCA. Other reports have described beneficial effects
      of successful rescue PTCA but adverse outcomes when PTCA is unsuccessful.
      METHODS: Using data from the Global Utilization of Streptokinase and Tissue
      Plasminogen Activator for Occluded Coronary Arteries (GUSTO-1) angiographic
      substudy, we compared clinical and angiographic outcomes of 198 patients selected
      for a rescue PTCA attempt with those of 266 patients with failed thrombolysis but
      managed conservatively and, for reference, with those of 1,058 patients with
      successful thrombolysis. RESULTS: Patients offered rescue PTCA had more impaired
      left ventricular function than those in whom closed vessels were managed
      conservatively. Rescue successfully opened 88.4% of closed arteries, with 68%
      attaining Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow. The
      interventions did not increase catheterization laboratory or postprocedural
      complication rates. Multivariate analysis identified severe heart failure to be a
      determinant of a failed rescue attempt. Successful rescue PTCA resulted in
      superior left ventricular function and 30-day mortality outcomes, comparable to
      outcomes in patients with closed IRAs managed conservatively, but less favorable
      than in patients in whom thrombolytic therapy was initially successful. The
      mortality rate after a failed rescue attempt was 30.4%; however, five of the
      seven patients who died after failed rescue PTCA were in cardiogenic shock before
      the procedure. CONCLUSIONS: Rescue PTCA tends to be selected for patients with
      clinical predictors of a poor outcome. It is effective in restoring patency.
      Patients who die after a failed rescue attempt are often already in extremis
      before the angioplasty attempt.

PMID- 9626829
TI  - Modifiable risk factors for vascular access site complications in the IMPACT II
      Trial of angioplasty with versus without eptifibatide. Integrilin to Minimize
      Platelet Aggregation and Coronary Thrombosis.
AB  - OBJECTIVES: This study was designed to identify potential predictors of vascular
      access site (VAS) complications in the large-scale Integrilin to Minimize
      Platelet Aggregation and Coronary Thrombosis (IMPACT) II trial, which studied
      angioplasty with versus without a new glycoprotein (GP) IIb/IIIa receptor
      inhibitor (eptifibatide). BACKGROUND: GP IIb/IIIa receptor inhibition during
      coronary interventions has been associated with excess VAS complications. If
      other predictors of VAS complications could be identified, they might be
      manipulated to reduce complications. METHODS: A total of 4,010 patients
      undergoing percutaneous transluminal coronary revascularization (PTCR) were
      randomized into one of three bolus/20- to 24-h infusion arms: placebo
      bolus/placebo infusion; 135-microg/kg body weight eptifibatide bolus/0.5
      microg/kg per min eptifibatide infusion; or 135-microg/kg eptifibatide bolus/0.75
      microg/kg per min eptifibatide infusion. Heparin during the procedure was weight
      adjusted and stopped 4 h before sheaths were removed. Logistic regression
      modeling was used to identify independent predictors of VAS complications.
      RESULTS: VAS complications were more common in patients treated with eptifibatide
      (9.9% vs. 5.9% placebo-treated patients, p < 0.001). Multivariate analysis
      identified eptifibatide therapy (p < 0.0001), advanced age (p = 0.0001), longer
      time to sheath removal (p = 0.0002), stent placement (with intense post-stent
      anticoagulation) (p = 0.0004), female gender (p = 0.0006), PTCR within 24 h of
      thrombolytic therapy (p = 0.002), larger heparin doses during PTCR (p = 0.009),
      major coronary dissection (p = 0.03) and placement of a venous sheath (p = 0.04)
      as independent predictors of VAS complications. CONCLUSIONS: VAS complications
      may be reduced by early sheath removal, by avoiding placement of venous sheaths
      and by limiting heparin dosing to avoid excessive activated clotting times. Early
      sheath removal during inhibition of platelet aggregation by eptifibatide is
      feasible.

PMID- 9626830
TI  - Selective suction and pressure-regulated retroinfusion: an effective and safe
      approach to retrograde protection against myocardial ischemia in patients
      undergoing normal and high risk percutaneous transluminal coronary angioplasty.
AB  - OBJECTIVES: We sought to study the safety, feasibility and efficacy of selective
      suction and pressure-regulated retroinfusion to protect against myocardial
      ischemia in patients undergoing normal risk and high risk balloon angioplasty.
      BACKGROUND: In a pig model of acute myocardial ischemia it was previously shown
      that use of selective suction and pressure-regulated retroinfusion was able to
      substantially preserve regional myocardial function during ischemia with a higher
      efficacy than that obtained with unselective synchronized retroperfusion.
      METHODS: In 42 patients with normal risk (n = 27) or high risk (n = 15)
      percutaneous transluminal coronary angioplasty (PTCA), alternate balloon
      inflations of the left anterior descending coronary artery (60 s) were either
      supported or not supported by selective suction and pressure-regulated
      retroinfusion of the anterior interventricular vein. In an additional group of 10
      patients with normal risk, retroinfusion was directly compared with autoperfusion
      during 10 min of ischemia. RESULTS: Balloon inflations without retroinfusion
      resulted in a decrease of regional myocardial function in the ischemic zone to
      13% of baseline. In contrast, regional myocardial function was preserved at 76%
      of baseline (p < 0.05) during balloon inflation supported by retroinfusion. This
      preservation of regional myocardial function by retroinfusion was maintained
      during 10 min of ischemia with at least similar efficacy compared with
      autoperfusion. With retroinfusion, hemodynamic variables were stabilized in
      normal risk and high risk patients. No complications related to the
      catheterization of the anterior interventricular vein using a femoral approach
      (95% success rate) were observed, and clinical follow-up after 3 to 6 months was
      uneventful with regard to the coronary intervention. CONCLUSIONS: Use of
      selective suction and pressure-regulated retroinfusion was feasible and safe and
      had a high efficacy for preserving regional myocardial function and hemodynamic
      variables during PTCA in normal risk and selected high risk patients.

PMID- 9626831
TI  - Unstable angina: good long-term outcome after a complicated early course.
AB  - OBJECTIVES: This study was performed to investigate the long-term outcome of
      patients with unstable angina within subgroups of the Braunwald classification.
      BACKGROUND: Long-term follow-up studies of patients with unstable angina are rare
      and date from more than two decades ago. This study was performed to establish
      the prognosis of different subgroups of patients with unstable angina (Braunwald
      criteria) during a 7-year follow-up period. METHODS: We registered a well defined
      group of 417 consecutive patients, admitted to the hospital for suspected
      unstable angina. The definite diagnosis was unstable angina in 282 patients (68%)
      and evolving myocardial infarction in 26; in 109 patients (26%), the symptoms
      were attributed to other or nonspecific causes. Patients with definite unstable
      angina were subclassified according to the Braunwald classification. Survival,
      survival without infarction and survival without infarction or intervention were
      determined for each class. RESULTS: After a median follow-up period of 94 months,
      the mortality rate in the first year was 6% and 2% to 3% in the following years.
      The frequency of revascularization was 47% in the first year, and that for
      myocardial infarction was 11% in the first year and 1% to 3% thereafter. The
      Braunwald classification appeared to be appropriate for risk stratification in
      the first year. However, at 7 years the event rates in all classes were similar.
      In particular, the Braunwald classification had no long-term impact on mortality
      or infarction rates. However, patients with acute angina at rest or
      postinfarction angina and patients with extensive anginal treatment had high
      intervention rates. CONCLUSIONS: To our knowledge, this study is the first to
      demonstrate that despite a complicated course during the first year, current
      management results in good long-term outcome in patients with unstable angina.

PMID- 9626832
TI  - Underestimation of extent and severity of coronary artery disease by dipyridamole
      stress thallium-201 single-photon emission computed tomographic myocardial
      perfusion imaging in patients taking antianginal drugs.
AB  - OBJECTIVES: This study evaluated the diagnostic value of dipyridamole plus low
      level treadmill exercise (dipyridamole stress) thallium-201 single-photon
      emission computed tomography (SPECT) in patients taking antianginal drugs.
      BACKGROUND: Dipyridamole stress is the major substitute for maximal exercise in
      patients referred for myocardial perfusion imaging. Although antianginal drugs
      are commonly suspended before exercise, dipyridamole stress is usually performed
      without discontinuing these drugs. METHODS: Twenty-six patients underwent two
      dipyridamole perfusion studies: the first without (SPECT-1) and the second with
      (SPECT-2) antianginal treatment. Twenty-one patients (81%) received calcium
      antagonists, 19 (73%) received nitrates, and 8 (31%) received beta-blockers.
      Eighteen of the patients underwent coronary angiography. Data are presented as
      the mean value +/- SD. RESULTS: Visual scoring yielded significantly larger and
      more severe reversible perfusion defects for SPECT-1 than for SPECT-2.
      Quantitative analysis showed larger perfusion defects on stress images of SPECT-1
      in the left anterior descending coronary artery (LAD) (25 +/- 21% vs. 17 +/- 15%,
      p = 0.003), left circumflex coronary artery (LCx) (56 +/- 35% vs. 48 +/- 36%, p =
      0.03) and right coronary artery (RCA) (36 +/- 27% vs. 25 +/- 24%, p = 0.008)
      territories. Individual vessel sensitivities in the LAD, LCx and RCA territories
      were 93%, 79% and 100% for SPECT-1 and 64%, 50% and 70% for SPECT-2,
      respectively. These differences were highly significant for the LAD (p = 0.004)
      and LCx (p = 0.00004) territories. The overall individual vessel sensitivity of
      SPECT-1 was significantly higher than that of SPECT-2 (92% vs. 62%, p =
      0.000003). Specificity was not significantly different in SPECT-1 compared with
      SPECT-2 (80% and 93%, p = 0.33). CONCLUSIONS: Continued use of antianginal drugs
      before dipyridamole plus low level treadmill exercise thallium-201 SPECT may
      reduce the extent and severity of myocardial perfusion defects, resulting in
      underestimation of coronary artery disease.

PMID- 9626833
TI  - Intravenous electron-beam computed tomographic coronary angiography for segmental
      analysis of coronary artery stenoses.
AB  - OBJECTIVES: We sought to identify and localize significant coronary stenoses on a
      segmental basis by electron-beam computed tomography (EBCT) and intravenous
      administration of a contrast agent. BACKGROUND: The clinical applicability and
      limitations of intravenous EBCT coronary angiography have not been defined.
      METHODS: EBCT was performed within 24 h of selective coronary angiography (SCA)
      in 28 patients (19 men and 9 women, mean [+/-SD] age 60 +/- 10 years). After
      examination for coronary calcium, EBCT coronary angiography was performed using
      overlapping slices (in-plane resolution 0.34 to 0.41 mm) with a nominal slice
      thickness of 1 mm. Based on quantitative analysis of SCA, lumen diameter
      narrowing > or = 50% (i.e., significant stenoses) was evaluated in 8 (major) or
      12 (including side branches) coronary artery segments, using both two-dimensional
      (tomographic) and three-dimensional (volume) data sets. RESULTS: Of the 330
      segments assessable by SCA, 237 (72%) were visualized by EBCT. The sensitivity
      (+/-SE) for detection of significant stenoses was 82 +/- 6%; specificity was 88
      +/- 2%; positive and negative predictive values were 57 +/- 7% and 96 +/- 2%,
      respectively; and overall accuracy was 87 +/- 2%. If only eight (major) coronary
      artery segments were considered, 194 (88%) of 221 segments were visualized, and
      the overall accuracy was 90 +/- 2%. Seven (18%) of 38 significantly stenotic
      segments were classified as having < 50% stenoses by EBCT. Six of these segments
      (86%), but only 9 (29%) of the 31 correctly classified stenotic segments, were
      severely calcified (area > 20 mm2, p = 0.02). In 23 (12%) of 199 nonstenotic
      segments falsely classified as having > or = 50% stenosis by EBCT, the lumen
      diameter was significantly smaller than that of the segments correctly classified
      as negative (mean [+/-SD] 1.5 +/- 0.8 vs. 2.9 +/- 1.1 mm, p < 0.001).
      CONCLUSIONS: Intravenous EBCT coronary angiography allows for accurate segmental
      evaluation of significant disease in the major coronary arteries and may be of
      value for ruling out significant disease. The main determinant of false negative
      results is substantial segmental calcification, whereas the main determinant of
      false positive results is small vessel size.

PMID- 9626834
TI  - Modulation of circulating cellular adhesion molecules in postmenopausal women
      with coronary artery disease.
AB  - OBJECTIVES: The present study examined the association of estrogen (E2) and the
      inflammatory response of endothelium in coronary artery disease (CAD) by
      measuring circulating cellular adhesion molecules (cCAMs) in subjects with
      atherosclerosis. BACKGROUND: Atherosclerotic plaque demonstrates features similar
      to inflammation. Endothelial cell activation by inflammatory cytokines induces
      expression of cellular adhesion molecules (CAMs), thereby perhaps augmenting
      leukocyte adhesion and recruitment and subsequent development of atherosclerosis.
      The incidence of CAD is lower in women; this may be due to the cardioprotective
      effects of E2. METHODS: Consecutive eligible subjects with CAD admitted for
      cardiac catheterization were studied. The groups evaluated were men,
      postmenopausal women receiving E2 replacement therapy (ERT), postmenopausal women
      not receiving ERT and premenopausal women. Control groups included men and women
      without CAD. Preprocedural blood samples were drawn from all groups. Measurements
      of cCAMs, E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and
      intercellular adhesion molecule-1 were performed by enzyme-linked immunoabsorbant
      assay. E2 levels were assessed by radioimmunoassay. RESULTS: We observed a
      statistically significant increase in all cCAMs in men with CAD and
      postmenopausal women with CAD not receiving ERT compared with postmenopausal
      women with CAD receiving ERT. Premenopausal women with CAD and postmenopausal
      women with CAD receiving ERT had a significant increase in VCAM-1 alone compared
      with the female control group. CONCLUSIONS: A possible mechanism by which E2
      exerts one of its cardioprotective effects is by limiting the inflammatory
      response to injury by modulating the expression of CAMs from the endothelium.

PMID- 9626835
TI  - B-mode ultrasound assessment of pravastatin treatment effect on carotid and
      femoral artery walls and its correlations with coronary arteriographic findings:
      a report of the Regression Growth Evaluation Statin Study (REGRESS).
AB  - OBJECTIVES: In this B-mode ultrasound study we assessed pravastatin treatment
      effects on carotid and femoral artery walls and investigated the correlations
      between the state and evolution of peripheral and coronary atherosclerosis.
      BACKGROUND: The Regression Growth Evaluation Statin Study (REGRESS) was an 11
      center, 2-year, double-blind, placebo-controlled, prospective study of 885 men
      with coronary artery disease (CAD) (total cholesterol 4 to 8 mmol/liter). The
      study primarily investigated pravastatin treatment effects on the coronary lumen.
      This report focuses on the 255 patients who participated in the REGRESS
      ultrasound study. METHODS: Carotid and femoral artery walls were imaged at
      baseline and at 6, 12, 18 and 24 months. Pravastatin treatment effect was defined
      as the difference in progression of the combined intima-media thicknesses (IMT)
      between treatment groups. RESULTS: Pravastatin treatment effects were highly
      significant (combined IMT: p = 0.0085; combined far wall IMT: p < 0.0001; common
      femoral artery far wall IMT: p = 0.004). Correlations between the IMTs of the
      arterial wall segments ranged from -0.17 to 0.81. Baseline correlations between
      IMT and percent coronary lumen stenoses ranged from 0.23 to 0.36. Baseline IMT
      correlated with the mean coronary segment diameter (r = -0.32, p = 0.001) and
      minimal coronary obstruction diameter (r = -0.27, p = 0.005). There were no
      individual correlations between IMT and coronary lumen variables (p > 0.30).
      CONCLUSIONS: Pravastatin treatment effects on carotid and femoral artery walls
      were observed. B-mode ultrasound imaging studies of peripheral arterial walls
      could not describe the state and evolution of the coronary lumen in the
      individual patient, but proved to be a highly suitable tool for the assessment of
      antiatherosclerotic properties of agents.

PMID- 9626836
TI  - Impaired myocardial vasodilation during hyperemic stress with dipyridamole in
      hypertriglyceridemia.
AB  - OBJECTIVES: This study sought to investigate the specific role of
      hypertriglyceridemia in the myocardial hyperemic stress with dipyridamole/rest
      flow ratio (MDR). BACKGROUND: Reduced MDR has been reported in
      hypercholesterolemic patients without evidence of ischemia. However, the specific
      role of hypertriglyceridemia in MDR has not been studied. METHODS: Fifteen
      nondiabetic normocholesterolemic hypertriglyceridemic patients and 13 age-matched
      control subjects were studied. Myocardial blood flow (MBF) during dipyridamole
      administration and baseline MBF in hypertriglyceridemic patients and control
      subjects were measured using positron emission tomography and nitrogen-13
      ammonia, after which the MDR was calculated. RESULTS: Baseline MBF (ml/min per
      100 g heart weight) in hypertriglyceridemic patients (mean +/- SD 73.6 +/- 24.1)
      did not differ significantly from that in control subjects (81.6 +/- 37.2). MBF
      during dipyridamole loading in hypertriglyceridemic patients (198 +/- 106) was
      significantly reduced compared with that in control subjects (313 +/- 176, p <
      0.05), as was the MDR (2.71 +/- 1.07 vs. 3.73 +/- 1.14, respectively, p < 0.05).
      Spearman rank-order correlation analysis showed a significant relation between
      plasma triglyceride concentration and MDR (r = -0.466, asymptotic SE 0.157, p =
      0.0125); however, no such significant relation was seen between total plasma
      cholesterol concentration and MDR (r = -0.369, asymptotic SE 0.130, p = 0.059).
      CONCLUSIONS: Impaired myocardial vasodilation was suggested in
      hypertriglyceridemic patients without symptoms and signs of ischemia.

PMID- 9626837
TI  - Scintigraphic assessment of regionalized defects in myocardial sympathetic
      innervation and blood flow regulation in diabetic patients with autonomic
      neuropathy.
AB  - OBJECTIVES: This study sought to evaluate whether regional sympathetic myocardial
      denervation in diabetes is associated with abnormal myocardial blood flow under
      rest and adenosine-stimulated conditions. BACKGROUND: Diabetic autonomic
      neuropathy (DAN) has been invoked as a cause of unexplained sudden cardiac death,
      potentially by altering electrical stability or impairing myocardial blood flow,
      or both. The effects of denervation on cardiac blood flow in diabetes are
      unknown. METHODS: We studied 14 diabetic subjects (7 without DAN, 7 with advanced
      DAN) and 13 nondiabetic control subjects without known coronary artery disease.
      Positron emission tomography using carbon-11 hydroxyephedrine was used to
      characterize left ventricular cardiac sympathetic innervation and nitrogen-13
      ammonia to measure myocardial blood flow at rest and after intravenous
      administration of adenosine (140 microg/kg body weight per min). RESULTS:
      Persistent sympathetic left ventricular proximal wall innervation was observed,
      even in advanced neuropathy. Rest myocardial blood flow was higher in the
      neuropathic subjects (109 +/- 29 ml/100 g per min) than in either the nondiabetic
      (69 +/- 8 ml/100 g per min, p < 0.01) or the nonneuropathic diabetic subjects (79
      +/- 23 ml/100 g per min, p < 0.05). During adenosine infusion, global left
      ventricular myocardial blood flow was significantly less in the neuropathic
      subjects (204 +/- 73 ml/100 g per min) than in the nonneuropathic diabetic group
      (324 +/- 135 ml/100 g per min, p < 0.05). Coronary flow reserve was also
      decreased in the neuropathic subjects, who achieved only 46% (p < 0.01) and 44%
      (p < 0.01) of the values measured in nondiabetic and nonneuropathic diabetic
      subjects, respectively. Assessment of the myocardial innervation/blood flow
      relation during adenosine infusion showed that myocardial blood flow in
      neuropathic subjects was virtually identical to that in nonneuropathic diabetic
      subjects in the distal denervated myocardium but was 43% (p < 0.05) lower than
      that in the nonneuropathic diabetic subjects in the proximal innervated segments.
      CONCLUSIONS: DAN is associated with altered myocardial blood flow, with regions
      of persistent sympathetic innervation exhibiting the greatest deficits of
      vasodilator reserve. Future studies are required to evaluate the etiology of
      these abnormalities and to evaluate the contribution of the persistent islands of
      innervation to sudden cardiac death complicating diabetes.

PMID- 9626838
TI  - Reduced responsiveness to endothelin-1 in peripheral resistance vessels of
      patients with syndrome X.
AB  - OBJECTIVES: This study sought to assess the contribution and action of nitric
      oxide and endothelin-1 in peripheral resistance vessels of patients with syndrome
      X. BACKGROUND: Patients with syndrome X may have a generalized disorder of
      vascular and endothelial function, promoting vasospasm. METHODS: Changes in blood
      flow responses to intrabrachial infusion of the endothelium-dependent
      vasodilators substance P and acetylcholine, the endothelium-independent nitric
      oxide donor sodium nitroprusside and the endothelin type A (ET(A)) receptor
      antagonist BQ-123 were assessed using venous occlusion plethysmography in 10
      patients with syndrome X and 10 matched control subjects. Vasoconstrictor
      responses to the nitric oxide synthase inhibitor L-N(G)-monomethyl arginine (L
      NMMA) and endothelin-1 were also determined. RESULTS: There were no significant
      differences in the responses to acetylcholine, substance P, sodium nitroprusside
      or BQ-123 between patients and control subjects. However, despite similar degrees
      of vasoconstriction in response to L-NMMA in both groups, endothelin-1 caused a
      reduction in forearm blood flow of only 20 +/- 2% in patients with syndrome X
      compared with 35 +/- 3% in matched control subjects at 90 min (p < 0.001).
      Although plasma endothelin-1 concentrations were not significantly higher in
      patients with syndrome X (4.8 vs. 4.0 pg/ml, p = 0.17), the vasoconstriction
      caused by endothelin-1 infusion correlated inversely with plasma endothelin-1
      concentrations (r = -0.51, p = 0.04). CONCLUSIONS: Patients with syndrome X had
      normal basal and stimulated nitric oxide activity and basal endogenous ET(A)
      receptor-mediated vascular tone. However, despite otherwise normal vascular
      function, there was reduced responsiveness to exogenous endothelin-1, possibly
      reflecting overactivity of this system and ET(A) receptor downregulation.

PMID- 9626839
TI  - Reversible restrictive left ventricular diastolic filling with optimized oral
      therapy predicts a more favorable prognosis in patients with chronic heart
      failure.
AB  - OBJECTIVES: We sought to assess whether in clinically stable patients with
      chronic heart failure (CHF) the prolongation (i.e., increase) of an initially
      short (< or = 125 ms) Doppler transmitral deceleration time (DT) of early filling
      obtained with long-term optimal oral therapy predicts a more favorable prognosis.
      BACKGROUND: It has been recently demonstrated that transmitral early DT is a
      powerful independent predictor of poor prognosis in patients with left
      ventricular dysfunction. However, DT may change over time according to loading
      conditions and medical treatment. METHOD: One hundred forty-four patients with
      CHF and a short DT (< or = 125 ms) underwent repeat Doppler echocardiographic
      study 6 months after the initial examination, while clinically stable with
      optimal oral therapy, and were then followed up for a mean period of 26 +/- 7
      months. RESULTS: After 6 months, DT had not changed in 80 patients (group 1),
      whereas it was significantly prolonged (> 125 ms) in the remaining 64 patients
      (group 2). Baseline Doppler echocardiographic features were similar in the two
      groups. No changes were found after 6 months in group 1, whereas group 2 showed a
      slight but significant (p < 0.01) reduction in end-systolic volume, an
      improvement in left ventricular ejection fraction (p < 0.01) and a decrease (p <
      0.01) in the degree of tricuspid regurgitation. During follow-up, 37% of patients
      in group 1 experienced cardiac death versus 11% in group 2 (p < 0.0005). By Cox
      model analysis, prolongation of a short DT emerged as the single best predictor
      of survival (chi-square 15.70). CONCLUSIONS: The prolongation of an initially
      short DT obtained with long-term optimal oral therapy predicts a more favorable
      outcome in clinically stable patients with CHF.

PMID- 9626840
TI  - Use of color kinesis for evaluation of left ventricular filling in patients with
      dilated cardiomyopathy and mitral regurgitation.
AB  - OBJECTIVES: We tested the feasibility of using analysis of color kinesis images
      to objectively assess global and regional left ventricular (LV) diastolic
      function in patients with dilated cardiomyopathy (DCM). In addition, the ability
      of this technique to track drug-induced changes on LV diastolic properties was
      studied. BACKGROUND: Diastolic dysfunction contributes to symptomatology in
      patients with DCM. The assessment of LV diastolic function using conventional
      Doppler echocardiography is indirect and is confounded by multiple variables.
      Moreover, the noninvasive evaluation of regional diastolic properties is
      difficult. In contrast, color kinesis directly tracks and color-encodes regional
      diastolic endocardial motion. METHODS: We studied 24 patients with DCM and mitral
      regurgitation (MR) and 24 age-matched normal subjects. Transmitral and pulmonary
      vein flow velocities were measured using pulsed Doppler echocardiography.
      Diastolic color kinesis images were used to calculate indexes of magnitude and
      timing of global and regional diastolic function. Diastolic asynchrony was
      evaluated in different subgroups of patients with DCM. The effects of drug
      infusions (nitroprusside and dobutamine) were also studied. RESULTS: Color
      kinesis indexes of global diastolic function showed significant differences
      between patients with DCM and normal subjects. Compared with Doppler indexes,
      color kinesis was less confounded by MR and was capable of differentiating
      between drug-induced lusitropic and vasodilator effects. Diastolic asynchrony was
      increased in patients with DCM and severe MR. CONCLUSIONS: Quantitative analysis
      of global and regional LV diastolic function in patients with DCM using color
      kinesis is feasible.

PMID- 9626841
TI  - Dobutamine stress echocardiography early after heart transplantation predicts
      development of allograft coronary artery disease and outcome.
AB  - OBJECTIVES: This study sought to determine the prognostic significance of serial
      dobutamine stress echocardiography (DSE) in new heart transplant recipients and
      to examine the relation between persistent wall motion abnormalities and the
      eventual development of coronary artery disease (CAD) as assessed by angiography.
      BACKGROUND: Allograft CAD is a major cause of graft failure. However, clinical
      diagnosis of the early disease remains difficult. The reasons for this include
      the diffuse nature of the disease and its predilection for the microvasculature,
      which are not easily detected by coronary angiography. Identifying patients at
      risk for the development of angiographic CAD early after transplantation may
      allow such patients to be targeted for aggressive treatment options to prevent
      subsequent cardiac events and early graft failure. METHODS: Twenty-two new heart
      transplant recipients were selected to undergo serial DSE at the time of their
      regularly scheduled endomyocardial biopsy. In addition, patients underwent
      scheduled annual coronary angiography. DSE was performed in 5-min stages with
      infusion of intravenous dobutamine at 5, 10, 20, 30 and 40 microg/kg body weight
      per min. RESULTS: Twenty-two patients had 91 DSE studies and 45 coronary
      angiograms. The patients were categorized into three groups based on the
      echocardiographic results. Group 1 (n = 7) had normal serial stress
      echocardiographic studies. Group 2 (n = 4) had transient inducible wall motion
      abnormalities. Group 3 (n = 11) developed persistent wall motion abnormalities.
      During a mean follow-up time of 32 +/- 11 months (range 5 to 50), 8 (73%) of 11
      patients in Group 3 developed events. The events included angiographic CAD (n =
      7), myocardial infarction (MI) (n = 1) and cardiac death (n = 3). The patient who
      developed an MI had a normal coronary angiogram. No cardiac event or angiographic
      disease occurred in either Group 1 or 2 patients. CONCLUSIONS: These results
      suggest that dobutamine-induced wall motion abnormalities, which are persistent
      in new heart transplant recipients, are predictive of the development of
      angiographic CAD, MI or death.

PMID- 9626842
TI  - Demonstration of a posterior atrial input to the atrioventricular node during
      sustained anterograde slow pathway conduction.
AB  - OBJECTIVES: This study sought to demonstrate electrophysiologic evidence for the
      existence of different anatomic atrial input sites of fast and slow conduction
      pathways in patients with dual atrioventricular (AV) node physiology. BACKGROUND:
      Although a separate posterior exit site exists for a retrograde slow AV node
      pathway, it remains unresolved whether a separate atrial input site into the AV
      node actually exists in patients with dual anterograde AV node pathway
      physiology. METHODS: In 10 patients with dual AV node pathway physiology, atrial
      pacing at three chosen drive cycle lengths (DCL1, DCL2 and DCL3) was performed at
      an anterior site (A) just above the His bundle recording site and at a posterior
      atrial site (P) just below the coronary sinus ostium. DCL3 was chosen as the one
      cycle length that resulted in a long AH interval consistent with slow pathway
      conduction. The stimulus to His bundle conduction times (SH) at both sites (SH(P)
      and SH(A), respectively) and their differences (deltaSH = SH(P) - SH(A)) at each
      of the three drive cycle lengths were analyzed. RESULTS: The mean +/- SD deltaSH
      values for DCL1 and DCL2 measured 9 +/- 16 and 8 +/- 18 ms, respectively, and the
      mean deltaSH value at DCL3 measured -34 +/- 24 ms, which was significantly
      different from the mean deltaSH values at DCL1 and DCL2 (both p < 0.05).
      CONCLUSIONS: The significant change in the deltaSH (SH(P) - SH(A)) value during
      slow pathway conduction could be accounted for by a corresponding shift of
      anterograde input from an anterior to a posterior entry site to the AV node.
      These findings support the notion that a separate anterograde entry site of the
      slow pathway does exist in patients with dual AV node pathway physiology.

PMID- 9626843
TI  - Transesophageal echocardiographic correlates of clinical risk of thromboembolism
      in nonvalvular atrial fibrillation. Stroke Prevention in Atrial Fibrillation III
      Investigators.
AB  - OBJECTIVES: This study explored the mechanisms linking clinical and precordial
      echocardiographic predictors to thromboembolism in atrial fibrillation (AF) by
      assessing transesophageal echocardiographic (TEE) correlations. BACKGROUND:
      Clinical predictors of thromboembolism in patients with nonvalvular AF have been
      identified, but their mechanistic links remain unclear. TEE provides imaging of
      the left atrium, its appendage and the proximal thoracic aorta, potentially
      clarifying stroke mechanisms in patients with AF. METHODS: Cross-sectional
      analysis of TEE features correlated with low, moderate and high thromboembolic
      risk during aspirin therapy among 786 participants undergoing TEE on entry into
      the Stroke Prevention in Atrial Fibrillation III trial. RESULTS: TEE features
      independently associated with increased thromboembolic risk were appendage
      thrombi (relative risk [RR] 2.5, p = 0.04), dense spontaneous echo contrast (RR
      3.7, p < 0.001), left atrial appendage peak flow velocities < or = 20 cm/s (RR
      1.7, p = 0.008) and complex aortic plaque (RR 2.1, p < 0.001). Patients with AF
      with a history of hypertension (conferring moderate risk) more frequently had
      atrial appendage thrombi (RR 2.6, p < 0.001) and reduced flow velocity (RR 1.8, p
      = 0.003) than low risk patients. Among low risk patients, those with intermittent
      AF had similar TEE features to those with constant AF. CONCLUSIONS: TEE findings
      indicative of atrial stasis or thrombosis and of aortic atheroma were
      independently associated with high thromboembolic risk in patients with AF. The
      increased stroke risk associated with a history of hypertension in AF appears to
      be mediated primarily through left atrial stasis and thrombi. The presence of
      complex aortic plaque distinguished patients with AF at high risk from those at
      moderate risk of thromboembolism.

PMID- 9626845
TI  - Influence of left ventricular geometric patterns on prognosis in patients with or
      without coronary artery disease.
AB  - OBJECTIVES: We sought to examine patterns of left ventricular (LV) geometry as
      determined by echocardiography and their association with mortality in patients
      with or without coronary artery disease (CAD). BACKGROUND: The independent
      prognostic role of LV geometry remains uncertain. METHODS: We performed a cohort
      study based on 988 consecutive patients who underwent both coronary arteriography
      for presumed CAD and echocardiography and were followed up for a mean of 9 years
      (range 5 to 13). Patients were classified into four LV geometry patterns: normal,
      concentric remodeling, eccentric LV hypertrophy (LVH) and concentric LVH.
      RESULTS: Patients with concentric LVH consistently showed the largest increase in
      LV posterior wall and septal thickness and LV mass index, as well as relative
      wall thickness (RWT), regardless of status of the coronary arteries. This pattern
      conferred the highest risk of both all-cause and cardiac mortality. Eccentric LVH
      moderately increased the risk of death compared with normal geometry; no
      substantial increase in mortality was noted in patients with concentric
      remodeling. When LV index and RWT were analyzed as continuous measures and
      considered in the same Cox proportional hazards model, increases in LV mass were
      independently associated with risk, but this outcome was less clear for RWT.
      CONCLUSIONS: In this series of patients referred to coronary angiography for
      suspected CAD, LVH conferred most of the predictive information from
      echocardiography. Patients with both LVH and abnormal RWT--concentric LVH-
      represent a group with the greatest mortality risk. Concentric remodeling may not
      be associated with increased risk of death because the predictive value of RWT is
      not as strong as for LV mass.

PMID- 9626844
TI  - Circadian blood pressure changes and myocardial ischemia in hypertensive patients
      with coronary artery disease.
AB  - OBJECTIVES: We sought to evaluate whether different circadian blood pressure (BP)
      changes could influence the occurrence of ischemic episodes in untreated and
      treated hypertensive patients with stable coronary artery disease (CAD).
      BACKGROUND: In hypertensive patients with CAD the occurrence of myocardial
      ischemia could be influenced by either high or low BP values. Ambulatory
      monitoring has shown that circadian BP profile is not uniform in hypertensive
      patients. METHODS: Twenty-one patients with a nighttime BP fall < 10%
      ("nondippers"), 35 with a nighttime BP fall between > 10% and < 20% ("dippers")
      and 14 with a nighttime BP fall > 20% ("overdippers") with CAD underwent
      simultaneous ambulatory BP and electrocardiographic monitoring before and during
      drug therapy with nitrates and atenolol or verapamil in a prospective,
      randomized, open, blinded end point design. RESULTS: Daytime BP was not
      significantly different among the groups both before and during therapy.
      Nighttime BP was different by definition. Treatment significantly reduced BP
      values in each group (p < 0.05). Daytime ischemic episodes did not differ among
      the groups either before or during therapy. Drug therapy significantly reduced
      daytime ischemia (p < 0.05). In untreated patients, nighttime ischemia was more
      frequent in nondippers than in dippers and overdippers (p < 0.05). Drug therapy
      significantly reduced nocturnal ischemia in nondippers (p < 0.05), had no
      significant effect in dippers and significantly increased nighttime ischemia in
      overdippers (p < 0.05). During treatment, nighttime ischemia was more frequent in
      overdippers than in dippers and nondippers (p < 0.05). The same results were
      achieved when ischemic episodes were defined with more restrictive criteria (ST
      segment depression > or = 2 mm). CONCLUSIONS: Circadian BP changes can influence
      the occurrence of myocardial ischemia in untreated and treated hypertensive
      patients with CAD. Nocturnal ischemia was found to be more frequent in nondippers
      among untreated patients and in overdippers among treated patients, potentially
      suggesting different therapeutic approaches based on circadian BP profile.

PMID- 9626846
TI  - Quantitative assessment of the operative results after extended myectomy and
      surgical reconstruction of the subvalvular mitral apparatus in hypertrophic
      obstructive cardiomyopathy using dynamic three-dimensional transesophageal
      echocardiography.
AB  - OBJECTIVES: The aim of this study was to examine the value of dynamic three
      dimensional (3D) transesophageal echocardiography (TEE) for the postoperative
      evaluation after extended myectomy and surgical reconstruction of the subvalvular
      mitral valve apparatus in patients with hypertrophic obstructive cardiomyopathy
      (HOCM). BACKGROUND: Two-dimensional imaging techniques such as echocardiography,
      computed tomography and magnetic resonance imaging have not been able to
      precisely quantify the effects of surgical therapy on the morphology of the left
      ventricular outflow tract (LVOT). METHODS: Multiplane TEE with 3D reconstruction
      was performed in 11 patients before and after the operation and in 16 normal
      control subjects for comparison. The preoperative maximal systolic pressure
      gradient in the LVOT was 69 +/- 59 mm Hg. The following variables were measured
      within the dynamic 3D data set: depth, width, length and cross-sectional area
      (CSA) gain caused by the myectomy trough, minimal CSA of the LVOT at each time
      point and its cyclic changes and maximal mitral leaflet deviation during systole.
      RESULTS: Functional class improved from 3.0 +/- 0.2 before the operation to 1.5
      +/- 0.6 after it. The maximal systolic pressure gradient in the outflow tract
      decreased to 26 +/- 21 mm Hg postoperatively (p < 0.001). Minimal CSA of the
      outflow tract increased from 1.1 +/- 1.2 to 3.8 +/- 1.9 cm2 postoperatively (p <
      0.001), similar to the value of the control group (4.2 +/- 1.5 cm2, p = NS). The
      area gain due to the myectomy trough was 1.3 +/- 1.0 cm2, corresponding to 48 +/-
      12% of the total operative area difference. Maximal systolic depth of the
      myectomy was 7 +/- 2 mm, maximal width was 20 +/- 8 mm and length was 28 +/- 7
      mm. Maximal deviation of the mitral leaflets fell from 15 +/- 7 to 6 +/- 7 mm
      postoperatively (p < 0.01). In five patients mass measurements of the
      intracavitary portion of the papillary muscle (PM) revealed an increase from 7.3
      +/- 1.0 to 12.1 +/- 2.5 g due to surgical mobilization of PMs (p < 0.01).
      CONCLUSIONS: 3D TEE quantifies the differences in outflow tract morphology before
      and after surgery for HOCM. This technique may have an impact on the planning of
      operative interventions and allow for the evaluation of its results.

PMID- 9626847
TI  - Outcome of pulmonary vascular disease in pregnancy: a systematic overview from
      1978 through 1996.
AB  - OBJECTIVES: Published reports were reviewed to evaluate the characteristics of
      peripartal management and the late pregnancy outcome in women with pulmonary
      vascular disease (PVD). BACKGROUND: Pulmonary hypertension poses one of the
      highest risks for maternal mortality, but actual data on the maternal and
      neonatal prognosis in this group are lacking. METHODS: Reports published from
      1978 through 1996 of Eisenmenger's syndrome (n = 73), primary pulmonary
      hypertension (PPH) (n = 27) and secondary vascular pulmonary hypertension (SVPH)
      (n = 25) complicating late pregnancy were included and analyzed using logistic
      regression analysis. RESULTS: Maternal mortality was 36% in Eisenmenger's
      syndrome, 30% in PPH and 56% (p < 0.08 vs. other two groups) in SVPH. Except for
      three prepartal deaths due to Eisenmenger's syndrome, all fatalities occurred
      within 35 days after delivery. Neonatal survival ranging from 87% to 89% was
      similar in the three groups. Previous pregnancies, timing of the diagnosis and
      hospital admission, operative delivery and diastolic pulmonary artery pressure
      were significant univariate (p < 0.05) maternal risk factors. Late diagnosis (p =
      0.002, odds ratio 5.4) and late hospital admission (p = 0.01, odds ratio 1.1 per
      week of pregnancy) were independent predictive risk factors of maternal
      mortality. CONCLUSIONS: In the last two decades maternal mortality was comparable
      in patients with Eisenmenger's syndrome and PPH; however, it was relevantly
      higher in SVPH. Maternal prognosis depends on the early diagnosis of PVD, early
      hospital admission, individually tailored treatment during pregnancy and medical
      therapy and care focused on the postpartal period.

PMID- 9626848
TI  - Autoimmune-associated congenital heart block: demographics, mortality, morbidity
      and recurrence rates obtained from a national neonatal lupus registry.
AB  - OBJECTIVES: The present study describes the demographics, mortality, morbidity
      and recurrence rates of autoimmune-associated congenital heart block (CHB) using
      information from the Research Registry for Neonatal Lupus. BACKGROUND: Isolated
      CHB detected at or before birth is strongly associated with maternal
      autoantibodies to 48-kD SSB/La, 52-kD SSA/Ro and 60-kD SSA/Ro ribonucleoproteins
      and is a permanent manifestation of the neonatal lupus syndromes (NLS). Available
      data are limited by the rarity of the disease. RESULTS: The cohort includes 105
      mothers whose sera contain anti-SSA/Ro or anti-SSB/La antibodies, or both, and
      their 113 infants diagnosed with CHB between 1970 and 1997 (56 boys, 57 girls).
      Of 87 pregnancies in which sufficient medical records were available,
      bradyarrhythmia confirmed to be CHB was initially detected before 30 weeks of
      gestation in 71 (82%) (median time 23 weeks). There were no cases in which major
      congenital cardiac anatomic defects were considered causal for the development of
      CHB; in 14 there were minor abnormalities. Twenty-two (19%) of the 113 children
      died, 16 (73%) within 3 months after birth. Cumulative probability of 3-year
      survival was 79%. Sixty-seven (63%) of 107 live-born children required
      pacemakers: 35 within 9 days of life, 15 within 1 year, and 17 after 1 year.
      Forty-nine of the mothers had subsequent pregnancies: 8 (16%) had another infant
      with CHB and 3 (6%) had a child with an isolated rash consistent with NLS.
      CONCLUSIONS: Data from this large series substantiate that autoantibody
      associated CHB is not coincident with major structural abnormalities, is most
      often identified in the late second trimester, carries a substantial mortality in
      the neonatal period and frequently requires pacing. The recurrence rate of CHB is
      at least two- to three-fold higher than the rate for a mother with anti-SSA/Ro
      SSB/La antibodies who never had an affected child, supporting close
      echocardiographic monitoring in all subsequent pregnancies, with heightened
      surveillance between 18 and 24 weeks of gestation.

PMID- 9626849
TI  - Hypothermic, closed circuit pericardioperfusion: a potential cardioprotective
      technique in acute regional ischemia.
AB  - OBJECTIVES: This study sought to determine whether infarct size can be reduced by
      hypothermic pericardioperfusion. BACKGROUND: We have shown that myocardial
      infarct size can be reduced by topical cooling of the heart. The present study
      tests whether myocardial cooling and protection can be produced by hypothermic
      pericardioperfusion using a catheter. METHODS: The catheter was sutured into the
      pericardial space of anesthetized rabbits. Beginning 30 min before coronary
      artery occlusion, the space was perfused with either chilled (n = 10) or body
      temperature (n = 10) fluid. The artery was occluded for 30 min and reperfused for
      3 h. RESULTS: After 30 min of pericardioperfusion, myocardial temperature was
      reduced to 34.1 +/- 0.9 degrees C in chilled hearts compared with 38.9 +/- 0.4
      degrees C in control hearts, p < 0.001, a reduction in myocardial temperature of
      approximately 5 degrees C. Risk areas were similar in both groups (32 +/- 4% left
      ventricle in cooled and 31 +/- 3% in control hearts, p = NS). However, infarct
      size in cooled hearts was significantly reduced by 49% (18 +/- 3% of risk area
      vs. 35 +/- 6%, p = 0.025). Tamponade did not develop, and there were no
      significant differences in heart rate, arterial pressure or body temperature
      between groups. CONCLUSIONS: A significant reduction in myocardial temperature,
      without the development of cardiac tamponade, can be attained using a pericardial
      catheter to cool the pericardial space. This reduction in temperature causes a
      significant reduction in necrotic damage. This technique might be used to cool
      and protect the heart as an adjunct to thrombolysis or during minimally invasive
      cardiac surgery.

PMID- 9626850
TI  - Effects of amiodarone and its active metabolite desethylamiodarone on the
      ventricular defibrillation threshold.
AB  - OBJECTIVES: We evaluated whether the reported difference in the ventricular
      defibrillation threshold (DFT) between short-term intravenous and oral amiodarone
      is due to the effect of amiodarone's active metabolite desethylamiodarone (DEA).
      BACKGROUND: Amiodarone is frequently used in patients with implantable
      cardioverter-defibrillator devices (ICD). Long-term oral amiodarone raises the
      DFT, but intravenous amiodarone has not been shown to have this effect. DEA, an
      active metabolite of amiodarone, has different electrophysiologic properties than
      its parent compound and may be responsible for the observed different effects of
      intravenous and oral amiodarone on DFT. METHODS: We ascertained the DFT in 24
      pigs randomized to receive intravenous amiodarone, DEA or vehicle. Defibrillation
      was delivered through a transvenous lead system using a biphasic waveform. The
      DFT was determined using an up-down DFT algorithm and defined as the average
      minimal energies resulting in successful defibrillation delivered from ascending
      and descending serial shocks. RESULTS: Amiodarone caused a dose-response increase
      in DFT (mean +/- SD) from 22.7 +/- 4.1 (baseline) to 26.1 +/- 2.9 (10 mg/kg body
      weight), p = 0.11, to 34.9 +/- 8.2 J (after an additional 15 mg/kg), p = 0.035.
      DEA (10 mg/kg) caused an increase in DFT from 20.5 +/- 6.3 to 33.9 +/- 13.6 J, p
      < 0.01. Addition of 15 mg/kg of DEA resulted in hemodynamic instability and thus
      DFT was not obtained. In the control group, DFT decreased from 26.8 +/- 7.7 at
      baseline to 23.1 +/- 7.4 (dose 1), p = 0.19, to 22.8 +/- 6.2 J (dose 2), p =
      0.18. CONCLUSIONS: DEA increases DFT by a greater amount than its parent drug
      amiodarone. There is an effect of intravenous amiodarone on DFT that is dose
      dependent.

PMID- 9626851
TI  - Functional effects of endogenous bradykinin in congestive heart failure.
AB  - OBJECTIVES: The purpose of this study was to determine the level and functional
      effects of endogenous bradykinin in congestive heart failure (CHF). BACKGROUND:
      There is experimental evidence that bradykinin is increased in several cardiac
      disease states. However, it is unknown whether plasma levels of bradykinin are
      elevated in CHF. Further, the cardiac and vascular responses to bradykinin in CHF
      are unclear. METHODS: The circulating levels of bradykinin and the effects of
      endogenous bradykinin were assessed in eight instrumented, conscious dogs both
      before and after pacing-induced CHF. RESULTS: Before CHF, the plasma bradykinin
      level was 53.1 +/- 12.4 pg/ml. Blocking endogenous bradykinin with HOE-140 (0.3
      mg/kg), a specific bradykinin B2-receptor antagonist, produced no significant
      alterations in heart rate, left ventricular (LV) end-systolic pressure (Pes),
      total systemic resistance (TSR), the time constant of LV relaxation (tau) or the
      maximal rate of LV filling (dV/dt(max)). However, coronary blood flow was
      significantly reduced (p < 0.05). LV contractile performance measured by the
      slopes of pressure-volume relations was unaffected. After induction of CHF, the
      plasma bradykinin level increased to 234.2 +/- 19.4 pg/ml (p < 0.05). Blocking
      endogenous bradykinin with HOE-140 reduced coronary blood flow and produced
      significant increases in Pes and TSR, prolonged tau, decreased dV/dt(max) and
      elevated minimal LV pressure and mean left atrial pressure. Furthermore, the
      slopes of pressure-volume relations (p < 0.05) were decreased, indicating
      depressed contractility with HOE-140 after CHF. CONCLUSIONS: Before CHF,
      endogenous bradykinin results in coronary dilation but has no effect on systemic
      arterial vasodilation or cardiac performance. After CHF, endogenous bradykinin is
      significantly increased and, acting through B2-receptors, produces coronary and
      arterial vasodilation and improves LV relaxation and contractile performance.
      Thus, endogenous bradykinin may play an important role in preserving
      cardiovascular function in CHF.

PMID- 9626852
TI  - Cyclooxygenase inhibition aggravates ischemia-reperfusion injury in the perfused
      guinea pig heart: involvement of isoprostanes.
AB  - OBJECTIVES: Postischemic contractile dysfunction in the heart may be due, in
      part, to isoprostanes, thought to accumulate during myocardial reperfusion. This
      study tested whether cyclooxygenase (COX) inhibitors increase the amount of
      isoprostanes and, consequently, lead to deterioration of postischemic heart
      function. BACKGROUND: Isoprostanes are bioactive prostaglandin-like compounds
      that are formed in vivo directly by free radical-catalyzed peroxidation of
      arachidonic acid. In particular, 8-isoprostaglandin (PG) F2alpha is a potent
      vasoconstrictor. METHODS: Isolated working guinea pig hearts underwent 30-min low
      flow ischemia followed by reperfusion, 15 min in a nonworking mode and 20 min
      performing pressure-volume work. Hearts were perfused with or without 100
      micromol/liter acetylsalicylic acid (ASA), 3 or 10 micromol/liter indomethacin or
      1 micromol/liter SQ 29548, a thromboxane-A2 (TxA2) receptor antagonist able to
      abolish the vasoconstrictive actions of 8-iso-PGF2alpha. External heart work
      (EHW) and coronary resistance were compared before and after ischemia. Coronary
      release and tissue content of 8-iso-PGF2alpha were also determined. RESULTS:
      During reperfusion, 8-iso-PGF2alpha release increased tenfold compared with the
      preischemic value in all groups. However, in ASA- and indomethacin-treated
      hearts, 8-iso-PGF2alpha levels were approximately 15-fold higher than in control
      hearts (5.4 vs. 0.35 pg/ml, respectively). Postischemic tissue levels of 8-iso
      PGF2alpha were also markedly higher: 215 (indomethacin) and 301 (ASA) pg/ml g dry
      weight versus 43 pg/mg dry weight for control hearts (p < 0.05). Treatment of
      hearts with COX inhibitor led to a reduction in recovery of EHW (40% vs. 71%, p <
      0.05) and seemed to be due to impaired myocardial oxygenation: Coronary venous
      oxygen was lower (67% of control values), whereas anaerobic metabolism (lactate
      release vs. pyruvate consumption) was enhanced. Coronary resistance was
      correspondingly elevated (164% of control values). SQ 29548 caused all variables
      to revert to control values. CONCLUSIONS: These data demonstrate that in the
      guinea pig heart, COX-inhibiting drugs exacerbate loss of cardiac function after
      ischemia. The enhanced production of isoprostanes favors coronary
      vasoconstriction and leads to myocardial oxygen deprivation.

PMID- 9626853
TI  - President's page: convocation address.

PMID- 9626854
TI  - Do sulfonylurea drugs limit coronary vasodilator reserve?

PMID- 9626855
TI  - Role (of assessment) of the human collateral circulation in (characterizing)
      ischemic adaptation to repeated coronary occlusion.

PMID- 9626856
TI  - Angiographic findings and outcome in diabetic patients with myocardial infarction
      -the GUSTO-I experience.

PMID- 9626857
TI  - Protective effect of prodromal angina before myocardial infarction.

PMID- 9626858
TI  - Warfarin versus aspirin in paroxysmal atrial fibrillation.

PMID- 9626859
TI  - Speech intelligibility in noise with fast compression hearing aids.
AB  - The effect of fast (syllabic) compression with overshoot reduction was studied in
      moderately hearing-impaired and in severely hearing-impaired listeners in quiet
      and in noisy situations. A test battery of daily masking noises was selected
      using multidimensional scaling techniques. Four relevant noises were selected: a
      multi-talker babble, the noise in an industrial plant, in a printing office and a
      city-noise background. The speech measurements show that only selected patients
      benefit from syllabic compression, i.e. listeners with a poor speech
      discrimination score. The effect in noisy surroundings was tested at the critical
      signal-to-noise ratio of each patient, showing whether they benefited from
      compression in the most critical condition or not. It turns out that the effect
      depends largely on the speech discrimination score and the modulation of the
      noise signal. When the speech discrimination score is good, compression tends to
      impair the results. When the speech discrimination score is poor, compression
      helps if the noise is modulated.

PMID- 9626860
TI  - Aminoglycoside ototoxicity and the medial efferent system: I. Comparison of acute
      and chronic gentamicin treatments.
AB  - Recently our laboratory has demonstrated, in the guinea pig (GP), that an
      intramuscular (i.m.) injection of a high dose of gentamicin (GM) (150 mg/kg), can
      reversibly block the contralateral efferent suppression of ipsilateral cochlear
      activity. The aims of the present study were: (1) to investigate this effect with
      lower doses of GM; and (2) to find out whether this effect could constitute an
      anticipatory sign of ototoxicity during a chronic GM treatment (60 mg/kg i.m., 10
      days). The function of the medial olivocochlear efferent system (MOES) was tested
      by recording the VIIIth nerve ensemble background activity (EBA) without and with
      contralateral low level (55 dB SPL) broadband noise stimulation. The results show
      a dose-dependent effect of GM on contralateral suppression, as the dose of 120
      mg/kg induced a smaller blockade of the MOES, compared to 150 mg/kg, and no
      blockade was observed with lower doses. During the ten-day treatment no
      significant changes in the EBA without acoustic stimulation, nor in contralateral
      efferent suppression were detected. GPs monitored over several weeks after the
      treatment showed progressive reduction of the EBA without contralateral
      stimulation parallel to reduced suppression coefficients of the EBA, and CAP
      threshold elevations, denoting impaired cochlear function. Thus, this study
      demonstrated that a chronic treatment with 60 mg/kg of GM, although ototoxic,
      does not affect the contralateral efferent suppression, at least before the
      development of ototoxicity.

PMID- 9626861
TI  - Aminoglycoside ototoxicity and the medial efferent system: II. Comparison of
      acute effects of different antibiotics.
AB  - Gentamicin (GM) has been shown to reversibly reduce the ability of contralateral
      noise to suppress ipsilateral cochlear activity, in a dose-dependent manner.
      However, during chronic administration of lower doses (60 mg/kg) the involvement
      of medial efferents could not be demonstrated. The purposes of the present study
      were to determine whether other aminoglycosides would display the same acute
      effects as GM and whether there was any correlation between their specificity and
      degree of cochlear and vestibular toxicity and their potency of blockade of the
      medial efferent system. Thus, we observed changes in ipsilateral ensemble
      background activity (EBA) of the VIIIth nerve without and with contralateral low
      level (55 dB SPL) broadband noise stimulation, in awake guinea pigs (GPs), before
      and after one single high-dose intramuscular injection of different
      aminoglycoside antibiotics (AAs) (gentamicin, amikacin, neomycin, netilmicin,
      streptomycin, tobramycin). For comparison, the effects of strychnine, a known
      antagonist of the efferent transmission and of cisplatin, an antineoplastic agent
      with cochleotoxic properties were also studied. Netilmicin displayed blocking
      properties similar to GM, although less pronounced, while amikacin and neomycin
      had no effect on medial efferent function. With tobramycin and streptomycin a
      decrease in suppression was usually associated with a reduction of the EBA
      measured without acoustic stimulation. However, with cisplatin, suppression was
      still effective when EBA was severely decreased. We could not observe specific
      effects of strychnine on medial efferent function. In conclusion, no correlation
      was found between specificity and degree of AA ototoxicity and their action on
      the medial efferent system.

PMID- 9626862
TI  - Tinnitus masking and depression.
AB  - In this pilot study 30 patients with annoying tinnitus completed tinnitus
      matching and the Beck Depression Inventory (BDI). A cluster analysis revealed
      three clusters of patients. Cluster one had relatively low depression and average
      results on tinnitus parameters. Cluster two displayed high depression scores and
      lower results on tinnitus parameters. The last small cluster had high depression
      scores and high results on tinnitus and hearing parameters. A curvilinear
      regression showed a U-shaped relation between the BDI and minimal masking level.
      The results are interpreted according to a diathesis stress model, in which a
      vulnerable person might develop tinnitus distress following a comparatively low
      degree of tinnitus and a more stress-tolerant person might bear higher degrees of
      tinnitus before seeking help. As a conclusion this may have implications for what
      treatment to recommend and most certainly should be accounted for in the
      assessment of patients.

PMID- 9626863
TI  - Renal MR angiography: a comprehensive approach.
AB  - Renal artery MR angiography has now emerged as a safe, accurate approach to renal
      arteriography. A comprehensive examination, including both three-dimensional (3D)
      dynamic gadolinium-enhanced and 3D phase contrast MRA techniques, allows
      evaluation of both the aorta-renal and splanchnic arterial anatomy as well as the
      hemodynamic significance of any stenoses identified. The 3D gadolinium-enhanced
      MRA technique produces a contrast arteriogram but without risks of iodinated
      contrast or ionizing radiation. The 3D phase contrast technique is a flow-based
      technique, which may show dephasing in the presence of hemodynamically
      significant stenoses. A comprehensive examination should also include T1- and T2
      weighted imaging for the assessment of potential neoplastic masses and the
      ubiquitous renal cysts. Through trial and error over the course of over a
      thousand examinations, this comprehensive approach to the MR evaluation of renal
      vascular pathology has emerged.

PMID- 9626864
TI  - Can MRCP replace ERCP?
AB  - Magnetic resonance cholangiopancreatography (MRCP) has replaced direct
      cholangiography and pancreatography in many instances. Its complete
      noninvasiveness and flexibility are less onerous for patients. For the use of
      screening as well as scrutiny, MRCP has played an important role in diagnosing
      various pathologies in this field. The usefulness of MRCP is not limited to
      anatomical evaluations; it can also yield physiologic and functional information.
      From a cost-performance basis, MRCP is undoubtedly superior to direct methods.
      Coupled with a cutting-edge MR system, MRCP has the potential to limit the use of
      invasive transpapillary and percutaneous methods merely to interventional
      purposes. In the near future, the emergence of interventional MR scanners will
      make MRCP even more competitive, and the replacement will be accelerated.

PMID- 9626866
TI  - Implementation and evaluation of a new pulse sequence for rapid acquisition of
      double inversion recovery images for simultaneous suppression of white matter and
      CSF.
AB  - We describe a fast double inversion recovery (DIR) imaging sequence that
      effectively attenuates signal from both white matter and cerebrospinal fluid
      (CSF). The pulse sequence uses a novel inversion/excitation scheme and fast spin
      echo readout to maximize scan efficiency. The white matter/CSF suppressed images
      can be acquired from the entire brain in approximately 6 minutes. Evaluation of
      the fast DIR sequence on patients with multiple sclerosis (MS) demonstrates high
      lesion conspicuity.

PMID- 9626865
TI  - Quantitative MRI of the brain in children with sickle cell disease reveals
      abnormalities unseen by conventional MRI.
AB  - Conventional MRI (cMRI) has shown that brain abnormalities without clinical
      stroke can manifest in patients with sickle cell disease (SCD). We used
      quantitative MRI (qMRI) and psychometric testing to determine whether brain
      abnormalities can also be present in patients with SCD who appear normal on cMRI.
      Patients 4 years of age and older with no clinical evidence of stroke were
      stratified by cMRI as normal (n = 17) or abnormal (n = 13). Spin-lattice
      relaxation time (T1) of gray and white matter structures was measured by the
      precise and accurate inversion recovery (PAIR) qMRI method. Patient cognitive
      ability was assessed with a standard psychometric instrument (WISC-III or WISC
      R). In all 30 patients with SCD, qMRI T1 was lower than in 24 age- and race
      matched controls, in cortical gray matter (P < .0006) and caudate (P < .0009), as
      well as in the ratio of gray-to-white matter T1 (P < .008). In the 17 patients
      who were shown to be normal by cMRI, qMRI T1 was still lower than in controls, in
      both cortical gray matter (P < .02) and caudate (P < .004). Histograms of voxel
      T1 show that the proportion of voxels with T1 values intermediate between gray
      and white matter (ie, consistent with encephalomalacia) was 9% higher than
      controls in patients shown to be normal by cMRI (P < .05) and 15% higher than
      controls in patients shown to be abnormal by cMRI (P < .0005). The full scale
      intelligence quotient (FSIQ) of all patients with SCD was 75, compared to the
      FSIQ of 88 in a historical control group of patient siblings (P < .001). The FSIQ
      of patients shown to be normal by cMRI was 79, significantly lower than the FSIQ
      of patient siblings (P < .04). The FSIQ of 71 in patients shown to be abnormal by
      cMRI was significantly lower than both the patient siblings (P < .005) and the
      patients shown to be normal by cMRI (P < .04). Patients shown to be abnormal by
      cMRI scored lower than patients shown to be normal by cMRI, specifically on the
      subtests of vocabulary (P = .003) and information (P = .03). Cognitive impairment
      is thus significant, even in patients with SCD who were shown to be normal by
      cMRI, suggesting that cMRI may be insensitive to subtle neurologic damage that
      can be detected by qMRI. Because cognitive impairment can occur in children
      normal by cMRI, our findings imply that prophylactic therapy may be needed
      earlier in the course of SCD to mitigate neurologic damage.

PMID- 9626868
TI  - Patterns of lingual tissue deformation associated with bolus containment and
      propulsion during deglutition as determined by echo-planar MRI.
AB  - Disordered lingual function is a common clinical attribute of patients with
      oropharyngeal dysphagia. To determine physiologic patterns of lingual tissue
      motion during swallowing, we imaged the actively deforming tongue during water
      bolus swallows with sequential single-slice sagittal orientation echo-planar
      imaging. At rest, with the bolus contained in the oral cavity before swallow
      initiation, the tongue displayed a characteristic curved configuration consisting
      of a convex surface (anterior to the bolus) in continuity with a concave surface
      (containing the bolus) and a posterior-located convex surface (comprising the
      tongue base). With swallow initiation, the previously deformed tongue underwent
      rapid biphasic displacement: (a) superior displacement of the anterior tongue and
      deepening of the midposterior-located bolus-containing concavity, resulting in a
      laterally beveled surface encompassing the bolus; and (b) retrograde displacement
      of the configured tissue, resulting in clearance of the bolus from the oral
      cavity to the oropharynx. These findings indicate that deglutitive tongue action
      can be depicted by echo-planar imaging as a series of deformative surface
      modifications, which are related to the activity of intrinsic and extrinsic
      lingual muscles.

PMID- 9626867
TI  - Flip angle dependence of experimentally determined T1sat and apparent
      magnetization transfer rate constants.
AB  - The purpose of this work was to develop a method for determining the T1sat and
      magnetization transfer (MT) rate constants by analyzing the slice-select flip
      angle dependent MT behavior of normal white and gray matter. The technique uses a
      high MT power, three-dimensional (3D) gradient-recalled echo (GRE) sequence, with
      a well chosen MT pulse frequency offset, such that the experimental conditions
      closely satisfy requisite assumptions for invoking a first order rate process for
      MT. Integral to this method is that the T1sat and MT ratio values are obtained
      under explicitly identical MT saturation conditions. The T1sat of white matter
      was found to be approximately 300 msec, and the MT rate constant was
      approximately 2.0 sec(-1). The T1sat of gray matter was approximately 500 msec,
      and the MT rate constant was 1.1 sec(-1). We also found a strong dependence of
      the MT rate constant on the slice-select flip angle used for the imaging
      sequence, independent of the MT saturation parameters. Strongly T1-weighted
      imaging sequences can result in the underestimation of the MT rate constant by
      50%. Practical technical suggestions for quantitative MT experiments are put
      forth.

PMID- 9626869
TI  - Histologic confirmation of microvascular hyperpermeability to macromolecular MR
      contrast medium in reperfused myocardial infarction.
AB  - A macromolecular MR contrast medium (MMCM) designed to permit histochemical
      staining and specific tissue localization, albumin-(biotin)10-(Gd-DTPA)25 (Bio
      Alb-Gd), was used in a rat model of reperfused myocardial infarction to confirm
      the presence and distribution of microvascular hyperpermeability. T1-weighted
      spin-echo images were acquired before and after administration of Bio-Alb-Gd. An
      avidin-biotin-complex (ABC) stain, specific for the biotinylated MR contrast
      medium, was used to define the MMCM distribution and to detect any regional
      change in microvascular permeability related to infarction. Immediately after Bio
      Alb-Gd administration, the infarcted region was enhanced, with greatest signal
      intensity noted at the rim and less at the center. There was a gradual increase
      in signal intensity of the initially hypointense central region. The steady
      increase in signal intensity of the central region suggested convection transport
      of MMCM through the interstitial space and its influx into cellular compartment
      after leakage from the vascular compartment. Histologic findings confirmed
      regional microvascular hyperpermeability corresponding to the site of infarction
      and a predominant rim distribution of the MMCM. Bio-Alb-Gd was identified at high
      microscopic power in the intravascular, interstitial, and intracellular spaces at
      the periphery of reperfused infarcted myocardium. Bio-Alb-Gd can be used as an MR
      contrast medium in reperfused infarcted myocardium to confirm the existence and
      to localize altered microvascular permeability to macromolecules. Bio-Alb-Gd
      contrast technique removes all the ambiguity between the distribution of the MR
      or other imaging contrast agent and the distribution of the substrate for
      histochemical staining.

PMID- 9626871
TI  - Quantification of mitral regurgitation with MR phase-velocity mapping using a
      control volume method.
AB  - Reliable diagnosis and quantification of mitral regurgitation are important for
      patient management and for optimizing the time for surgery. Previous methods have
      often provided suboptimal results. The aim of this in vitro study was to evaluate
      MR phase-velocity mapping in quantifying the mitral regurgitant volume (MRV)
      using a control volume (CV) method. A number of contiguous slices were acquired
      with all three velocity components measured. A CV was then selected, encompassing
      the regurgitant orifice. Mass conservation dictates that the net inflow into the
      CV should be equal to the regurgitant flow. Results showed that a CV, the
      boundary voxels of which excluded the region of flow acceleration and aliasing at
      the orifice, provided accurate measurements of the regurgitant flow. A smaller CV
      provided erroneous results because of flow acceleration and velocity aliasing
      close to the orifice. A large CV generally provided inaccurate results because of
      reduced velocity sensitivity far from the orifice. Aortic outflow, orifice shape,
      and valve geometry did not affect the accuracy of the CV measurements. The CV
      method is a promising approach to the problem of quantification of the MRV.

PMID- 9626870
TI  - Quantification of in-plane motion of the coronary arteries during the cardiac
      cycle: implications for acquisition window duration for MR flow quantification.
AB  - Motion of the coronary arteries during the heart cycle can result in image
      blurring and inaccurate flow quantification by MR. This condition applies
      particularly for longer acquisition windows that are typical of breath-hold
      coronary flow measurements. To determine the sensitivity of the technique to in
      plane motion of different coronary arteries, the temporal variation in coronary
      position was measured in a plane perpendicular to the proximal portion of the
      vessel. The results indicated the presence of substantial displacement of the
      coronary arteries within the cardiac cycle, with a magnitude of motion
      approximately twice as large for the right as for the left coronary arteries. An
      estimation of the resulting vessel blurring was calculated, showing that the
      duration of the acquisition window for high spatial resolution coronary flow
      acquisitions should be less than 25 to 120 msec, depending on the specific
      coronary artery studied. In addition, these data specify optimal acquisition
      window placement for high resolution coronary angiography.

PMID- 9626872
TI  - Slice-selective fat saturation in MR angiography using spatial-spectral selective
      prepulses.
AB  - Presaturation of fat signals by frequency-selective radiofrequency (RF) pulses is
      often applied in MR angiography to improve the visualization of the blood
      vessels. Unfortunately, standard fat saturation methods might cause a
      considerable reduction of the blood signal in the measured slices. This effect is
      caused by an attenuation of blood magnetization in remote tissue regions with
      water protons showing a similar Larmor frequency as the fat protons in the
      recorded slice. The affected blood water protons subsequently flow into the
      recorded slice and provide low signal intensity. Suitable spatial-spectral
      selective methods for slice-selective fat saturation were developed to avoid this
      unwanted effect. A spatial-spectral fat saturation technique was compared with a
      corresponding only spectrally selective approach. Both saturation techniques were
      included in a standard two-dimensional (2D) cine sequence and applied in
      angiographic examinations of the thighs. The results indicate that spatial
      spectral saturation (acting slice selectively) leads to a clearly higher blood
      signal intensity in fat-suppressed MR angiography compared with standard
      techniques, especially in measurements performed during the systolic phase of the
      cardiac cycle.

PMID- 9626873
TI  - Variations in blood flow waveforms in stenotic renal arteries by 2D phase
      contrast cine MRI.
AB  - Waveform variations in blood flow measurements through stenotic renal arteries
      have been reported already with echo Doppler studies. We studied these variations
      with MRI in 14 patients (mean age, 60 years) with suspected renal arterial
      stenosis (24 patent arteries, four occluded). Flow measurements were successful
      in 15 arteries and unsuccessful in nine, due to practical limitations. Seven
      healthy younger volunteers (mean age, 28 years) and five healthy older volunteers
      (mean age, 58 years) were recruited for comparison purposes. In patients, the
      severity of stenoses was also assessed by digital subtraction angiography and
      intraarterially measured transstenotic pressure drops. We found flow patterns to
      be statistically significantly (P < 0.01) age-related. Younger healthy subjects
      showed shorter wave duration, higher diastolic flow, and total blood flow per
      minute. Also, with increasing stenosis severity, the systolic wave became more
      damped and the systolic wave duration became statistically significantly (P =
      .03) longer.

PMID- 9626874
TI  - Value of image subtraction in 3D gadolinium-enhanced MR angiography of the renal
      arteries.
AB  - The objective of this study was to evaluate quantitatively and qualitatively the
      effect of image subtraction on the image quality of three-dimensional (3D)
      gadolinium-enhanced MR angiograms of the renal arteries. Breath-hold 3D
      gadolinium MR angiography (MRA) as well as conventional contrast angiography of
      the renal arteries was performed on 20 patients with suspected renovascular
      hypertension. MR angiograms were acquired before and during dynamic infusion of
      gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA). Contrast-enhanced
      images were compared with images that had undergone voxel-by-voxel signal
      intensity subtraction of contrast-enhanced data from precontrast data. One false
      positive finding for significant renal artery stenosis was recorded with MRA
      using conventional angiography as the gold standard. Image subtraction did not
      alter the diagnosis at MRA in any case. The mean contrast-to-noise ratio (CNR)
      was significantly higher (P < .05) on the subtraction MR angiograms compared to
      the nonsubtracted MR angiograms. There was no significant difference in the
      signal-to-noise ratio (SNR). Qualitative analysis revealed a significant
      improvement in image quality after image subtraction with respect to
      visualization of the distal renal arteries. In conclusion, image subtraction
      improves the quality of renal MRA in terms of both CNR and visualization of the
      distal renal arteries.

PMID- 9626875
TI  - Contrast-enhanced 3D MRA with centric ordering in k space: a preliminary clinical
      experience in imaging the abdominal aorta and renal and peripheral arterial
      vasculature.
AB  - The objective of this study was to determine the clinical utility of a contrast
      enhanced, centric reordered, three-dimensional (3D) MR angiography (MRA) pulse
      sequence in imaging the abdominal aorta and renal and peripheral lower extremity
      arteries. Twenty-eight MRA studies were performed on 23 patients and four
      volunteers at 1.5 T using a 3D contrast-enhanced, centric reordered pulse
      sequence. In 20 patients, the abdominal aorta and renal arteries were imaged, and
      in seven patients, the lower extremity arteries were imaged. In 19 patients, a
      total of 51 renal vessels were evaluated (33 renal arteries using .1 mmol/kg of
      gadopentetate dimeglumine and 18 renal arteries using .2 mmol/kg of gadoteridol).
      A total of 70 peripheral arterial segments were assessed using .2 mmol/kg of
      gadoteridol. Correlation with conventional angiography was made for the following
      14 cases: renal artery stenosis (four cases), abdominal aortic stenosis (one
      case), arteriovenous fistula in a transplant kidney (one case), renal
      arteriovenous malformation (one case), common iliac artery aneurysms (one case),
      and peripheral lower extremity (six cases). Of the 70 peripheral arterial
      segments evaluated, in 35, there was correlation with x-ray angiography. The mean
      percent of aortic signal enhancement was significantly higher in the .2 mmol/kg
      dose group (370.8 +/- 190.3) than in the .1 mmol/kg dose group (184.5 +/- 128.9)
      (P = .02). However, there was no apparent difference between the two doses for
      visualization of the renal and accessory renal arteries. There was concordance
      between the contrast-enhanced 3D MRA studies and conventional angiography in all
      cases of renal artery and peripheral arterial stenoses and occlusions, including
      visualization of reconstituted peripheral arterial segments. There was no
      evidence of spin dephasing effects at sites of stenoses on the 3D contrast
      enhanced MRA studies. Contrast-enhanced, centric reordered, 3D MRA can rapidly
      image the abdominal aorta and renal and accessory renal arteries, as well as
      peripheral lower extremity arteries, with high resolution. Accurate depiction of
      the vascular lumen at sites of stenosis is made because of the lack of spin
      dephasing effects, even with hemodynamically significant stenoses. Additional
      larger clinical trials are required with this promising technique.

PMID- 9626877
TI  - Characterization of atherosclerotic plaque components by high resolution
      quantitative MR and US imaging.
AB  - High resolution MRI at 3 T and US imaging at 50 MHz were used for atherosclerotic
      plaque characterization. For 14 excised segments of human arteries, conventional
      MR and US images, quantitative MR T2 maps, US integrated attenuation (IA) maps,
      and histologic sections were produced and compared. The MR T2 and US attenuation
      mean values estimated in selected regions of interest were related with tissue
      type as identified on histologic sections. Significant distinction between media
      or collagen and lipid or collagen lipidic plaque was achieved with both
      techniques (MR: P < .001; US: P < .01). Significant distinction was obtained
      between media and collagen (P < .0001) and between iliac and aortic media (P <
      .05) with MR T2 but not with IA. MR and US native and parametric images, with
      different sensitivities to tissue type, provide complementary information useful
      for quantitative plaque characterization.

PMID- 9626876
TI  - Contrast-enhanced 3D-TOF MRA of peripheral vessels: intravascular versus
      extracellular MR contrast media.
AB  - MR contrast media have been used to improve MR angiography (MRA). Their effect
      has been particularly beneficial for extracranial MRA. This study evaluated the
      efficacy of a new formulation of ultrasmall superparamagnetic iron oxide
      particles (USPIO) on three-dimensional (3D) time of flight (TOF) MRA in the
      pelvis and lower limb circulation. Each of six dogs received 3 mg/kg of USPIO and
      .2 mmol/kg of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) bis
      methylamide (BMA) by intravenous infusion on separate examinations. Precontrast
      and postcontrast 3D-TOF MRA images of the lower extremities were acquired over
      the course of 45 minutes postinjection. Signal intensity (SI) was measured on
      axial views along the external iliac, femoral, and popliteal arteries. USPIO
      provided clear demarcation of the major primary, secondary, and tertiary vessels
      and the improved contrast-to-noise ratio (CNR) was maintained for 45 minutes. Gd
      DTPA-BMA provided less signal enhancement than USPIO. The increase in CNR with
      this agent had significantly declined by 15 minutes after injection. The major
      vessels could no longer be visualized at 30 and 45 minutes after injection of Gd
      DTPA-BMA This study demonstrates the efficacy of USPIO as a contrast medium for
      3D-TOF MRA. It was concluded that USPIO provided effective and persistent
      enhancement of the peripheral vessels.

PMID- 9626878
TI  - Three-dimensional low dose gadolinium-enhanced peripheral MR venography.
AB  - Our initial experience with low dose contrast-enhanced (LCE) peripheral MR
      venography (MRV) is presented. Five subjects were studied using three-dimensional
      (3D) fast imaging with a steady-state precession (FISP) sequence. A dose of 60 ml
      of gadopentetate dimeglumine diluted 1:20 was used. A tourniquet was applied
      during lower extremity MR venography. The venous anatomy was well depicted with
      the 3D LCE technique in all subjects. Compared to the two-dimensional (2D) time
      of-flight (TOF) technique, acquisition time of 3D LCE MRV was much shorter,
      images looked sharper, and more veins could be seen. It is not affected by in
      plane saturation and can be performed repeatedly because of the low dose of
      contrast. This technique holds promise for the detection of venous thrombosis and
      other disorders.

PMID- 9626879
TI  - High resolution MRI of MCF7 human breast tumors: complemented use of iron oxide
      microspheres and Gd-DTPA.
AB  - The differential capacity of iron oxide microspheres and of gadolinium
      diethylenetriamine pentaacetic acid (Gd-DTPA) to serve as contrast agents that
      can map the microcirculation of MCF7 human breast cancer implanted in nude mice
      has been examined by high resolution MRI. Modulation of signal intensity in T2*
      weighted, gradient-echo images after iron oxide administration and the temporal
      signal enhancement after Gd-DTPA administration were monitored and analyzed at a
      spatial resolution of 98 x 98 x 500 microm and 195 x 390 x 1,000 microm,
      respectively. The pathophysiologic features revealed in the contrast-enhanced
      images were analyzed in reference to those obtained from the corresponding high
      resolution T2-weighted, spin-echo images and from histologic sections stained
      with hematoxylin and eosin and with an endothelial cell marker. The results
      showed that iron oxide microspheres can aid in the characterization of gross
      histopathologic features and in the assessment of the distribution of the
      microvasculature, whereas Gd-DTPA estimates the permeability of the microvessels
      to this agent and determines the cellularity (cell volume fraction) in the
      vicinity of the vessels.

PMID- 9626880
TI  - Hepatic T2-weighted MRI: a prospective comparison of sequences, including breath
      hold, half-Fourier turbo spin echo (HASTE).
AB  - The purpose of this study was to quantitatively compare the hepatic contrast
      characteristics of conventional spin-echo (CSE) and fast spin-echo (FSE)
      sequences with breath-hold T2-weighted images acquired with half-Fourier turbo
      spin echo (HASTE). Forty-five patients were examined with a phased-array surface
      coil. Nineteen patients had focal hepatic lesions, including eight malignant
      tumors, 10 cavernous hemangiomas, and one hepatic adenoma. Twenty-six patients
      had no focal hepatic lesions. T2-weighted images with comparable TE were acquired
      with CSE, FSE, and HASTE pulse sequences. Signal-to-noise ratio (SNR) and
      contrast-to-noise ratio (CNR) for liver, spleen, and lesions were measured. FSE
      demonstrated significantly better quantitative performance than CSE for liver
      spleen CNR (P .0084). No statistically significant difference was demonstrated
      between FSE and CSE for liver or spleen SNR. FSE demonstrated clear scan time and
      resolution advantages over CSE. HASTE performed significantly poorer than CSE and
      FSE for liver-spleen CNR (P < .0001), liver SNR (P = .0002 for CSE and P < .0001
      for FSE), and spleen SNR (P < .0001). Optimized FSE images with a short echo
      train length performed comparably to CSE images of equivalent TE. Liver-lesion
      CNR was suppressed on HASTE images, suggesting that long echo train length FSE
      sequences could diminish solid lesion detection compared to CSE and short echo
      train length FSE.

PMID- 9626881
TI  - Assessment of hepatic portal perfusion using T2 measurements of Gd-DTPA.
AB  - Recently, perfusion imaging has been of increasing interest in MRI. We applied
      this method for semiquantitative evaluation of hepatic parenchymal portal blood
      flow in patients with diffuse liver damage. Twenty patients with diffuse hepatic
      damage were divided according to the Child's Classification and studied.
      Gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) was administered into
      the superior mesenteric artery (SMA), and a dynamic series of T2*-weighted fast
      low angle shot (FLASH) images was obtained. We evaluated relative regional portal
      blood volume (rrPBV), mean transit time (MTT), and relative regional portal blood
      flow (rrPBF). The relationship between the rrPBV, rrPBF, and plasma indocyanine
      green retention rate test at 15 minutes (ICGR15 was also evaluated in 12
      patients. Both rrPBF and rrPBV are significantly decreased in Child B & C
      patients compared with Child A patients. On the other hand, the MTT is
      significantly prolonged in Child B & C patients compared with Child A patients.
      Significant correlations were also noted between rrPBV and ICGR15 and between
      rrPBF and ICGR15. By means of selective catheterization into the SMA, we were
      able to estimate rrPBV, rrPBF, and MTT. This method may play a clinical role for
      assessment of regional portal perfusion in various diseases with diffuse liver
      damage.

PMID- 9626882
TI  - The value of respiratory triggered T2-weighted turbo spin-echo imaging of the
      liver using a phased array coil.
AB  - The purpose of this study was to evaluate the value of the respiratory triggered
      turbo spin-echo (TSE) technique for T2-weighted MRI of liver lesions. Fifty-nine
      patients (32 men, 27 women; mean age, 63.3 years) with focal hepatic lesions were
      prospectively studied with MRI at 1.5 T with use of a body phased array coil. In
      the first 15 patients, breath-hold TSE, respiratory triggered TSE, and
      conventional nonrespiratory triggered TSE T2-weighted imaging were compared.
      Because nonrespiratory triggered TSE imaging was significantly inferior (P < .01)
      to breath-hold or respiratory triggered images, breath-hold and respiratory
      triggered TSE T2-weighted images were compared in the remaining 44 patients.
      Images were analyzed quantitatively by measuring the liver signal-to-noise ratio
      and the lesion-liver and spleen-liver contrast-to-noise ratios and qualitatively
      by evaluating the lesion conspicuity, liver parenchymal homogeneity, and
      sharpness of intrahepatic vessels. The imaging time was 26 seconds for breath
      hold TSE imaging, 49 to 219 seconds (mean, 149 seconds) for the respiratory
      triggered TSE imaging, and 79 to 379 seconds (mean, 239 seconds) for the
      nonrespiratory triggered TSE imaging. Quantitatively, the signal-to-noise ratio
      of the liver for breath-hold imaging was comparable to that for respiratory
      triggered imaging. The lesion-liver and liver-spleen contrast-to-noise ratios for
      the respiratory triggered images were greater by 37% and 39%, respectively, than
      for the breath-hold T2-weighted TSE images. Qualitatively, the respiratory
      triggered images showed lower frequency of image artifact, better lesion
      conspicuity, and greatly superior depiction of intrahepatic structures compared
      with the breath-hold T2-weighted TSE images. The respiratory triggered T2
      weighted TSE technique provides better quality liver images than the breath-hold
      TSE technique or nonrespiratory triggered technique within a reasonable
      acquisition time.

PMID- 9626883
TI  - Dynamic evaluation of the hepatic uptake and clearance of manganese-based MRI
      contrast agents: a 31P NMR study on the isolated and perfused rat liver.
AB  - This spectroscopic study compares the mechanisms of the hepatic uptake of
      manganese chloride (MnCl2) and manganese dipyridoxyl diphosphate (MnDPDP).
      Alterations of the phosphorus-31 (31P)-NMR spectrum of the intracellular
      adenosine 5'-triphosphate (ATP) are used to monitor the internalization of
      manganese by the isolated and perfused rat liver. Mn2+ delivered as MnCl2 in the
      perfusate rapidly enters the hepatocytes, where it strongly interacts with ATP,
      inducing a broadening of the 31P lines. The inhibition of the process by
      nifedipine confirms that manganese ions cross the cellular membrane at least
      partly through Ca2+ channels. MnDPDP induces weaker but still significant changes
      of the ATP spectrum. The inability of pyridoxine to compete for the uptake of
      manganese confirms that the vitamin B6 carrier is not involved in the
      internalization process of the paramagnetic complex. Finally, preincubation of
      MnDPDP with blood does not increase the extent of the dissociation. The
      alterations of the 31P spectrum of the liver subsequent to the administration of
      MnDPDP are attributable to a fraction of free Mn2+ released by the chelate and
      delivered to the hepatocytes.

PMID- 9626885
TI  - Determination of sample time for T1 measurement.
AB  - In spin-lattice relaxation time measurements, the relaxation time T1 is estimated
      from measuring the longitudinal magnetization during its return to thermal
      equilibrium from an initial (nonequilibrium) state. T1 estimation error depends
      on a number of factors, including the sample spacing, number of sample points,
      target T1 range, etc. We describe here a sample-time determination method based
      on the principles of optimal experimental design. A two-parameter model and a
      more general three-parameter model of the general T1 measurement experiment are
      used in this study. Both linear and power-law sample spacing strategies are
      evaluated. The proposed method formulates the sample-time determination problem
      in closed form expressions that allow for easy calculation of optimum sample
      times, if a prior T1 estimate or a probable T1 distribution over the target range
      is given. Valuable insights can be gained from evaluation of these expressions
      concerning the relationship of T1 estimation error and the sample spacing, number
      of sample points, target T1 range, etc.

PMID- 9626884
TI  - Sequential use of ferumoxide particles and gadolinium chelate for the evaluation
      of focal liver lesions on MRI.
AB  - This study describes the sequential use of ferumoxide (superparamagnetic iron
      oxide) particles and nonspecific extracellular gadolinium chelate (Gd) for
      evaluation of focal liver lesions on MRI to evaluate order of contrast
      administration and imaging effect of the first contrast agent on sequences
      acquired after the second contrast agent. Thirteen patients underwent MR
      examinations that included ferumoxide and Gd. The order and timing of
      administration were as follows: separate sessions (three patients; Gd study 4-19
      days before ferumoxide study), same session, Gd first (seven patients; Gd study 1
      2 hours before ferumoxide study), and same session, ferumoxide first (three
      patients; ferumoxide administered less than 1 hour before Gd study). Postcontrast
      sequences were reviewed in a randomized, blinded fashion by two separate
      investigators. Determination was made regarding whether (a) the presence of the
      first agent administered could be detected on sequences obtained after the second
      agent and (b) the presence of the first agent interfered with the image quality
      of those sequences. No evidence for the presence of Gd was appreciated by either
      observer on postferumoxide sequences acquired in separate session studies. In
      same session, Gd first studies, the presence of Gd was observed in six of seven
      patients on T1-weighted spoiled gradient-echo (SGE) images obtained after
      ferumoxide administration. The presence of Gd was not apparent in seven of seven
      patients on T2-weighted fat-suppressed images obtained after ferumoxide. In same
      session, ferumoxide first studies, the presence of ferumoxide was appreciated on
      post-Gd sequences in two of three patients. The presence of ferumoxide did not
      appreciably diminish image quality on those sequences. Exact agreement was
      achieved by the independent investigators. Our results suggest that Gd and
      ferumoxide can be administered sequentially within one study session without
      substantial loss of diagnostic information obtained on sequences performed after
      administration of the second contrast agent. Administrating Gd first resulted in
      less of an effect of the visualization of the first agent on sequences acquired
      after the second agent.

PMID- 9626886
TI  - Uptake of mangafodipir trisodium in liver metastases from endocrine tumors.
AB  - The purpose of the study was to investigate retrospectively whether mangafodipir
      trisodium (MnDPDP) can enhance the liver metastases from endocrine tumors.
      Thirteen patients with endocrine tumors and liver metastases underwent T1
      weighted spin-echo (SE) and turbo gradient-echo (GRE) MRI conducted before and 20
      to 60 minutes after i.v. infusion of MnDPDP. Additional 24-hour-delay scans were
      performed in 8 of 13 patients. MR signal intensity (SI) was measured in liver
      parenchyma and metastases, which was then related to that of paraspinal muscle. A
      total of 30 lesions on precontrast and postcontrast images and 18 lesions on 24
      hour-delay images were measured. An enhancement by 49% in SE and 40% in GRE
      images (P = .0001) was observed in tumor tissues after MnDPDP infusion. In 24
      hour-delay images, the SI of the lesions remained relatively high, but in liver
      parenchyma, it decreased significantly, and the tumor-liver tissue contrast was
      reduced.

PMID- 9626887
TI  - Preclinical assessment of hepatocyte-targeted MR contrast agents in stable human
      liver cell cultures.
AB  - Much effort has been expended in the search for hepatocyte-specific MR contrast
      agents to improve the detection and characterization of liver tumors. The purpose
      of this study was to establish human hepatocyte cell cultures to preclinically
      assess hepatocyte-targeted magnetopharmaceuticals. Cultured human hepatocytes
      were sandwiched between two layers of collagen preserving both hepatocyte
      function and morphology over prolonged period of time. Cultures (n = 37) were
      subsequently used to test different fluorescinated MR contrast agents. Plain and
      rhodaminated monocrystalline iron oxide particles (MION and MION-rh) and
      asialoglycoprotein-receptor-specific rhodaminated asialofetuin coupled to MION
      (MION-ASF-rh) were prepared. Competition experiments of these agents were
      performed with D(+)-galactose to study the specificity of galactose-mediated cell
      uptake. To assess the impact of cell integrity on cell uptake, functional
      experiments with CCl4 were performed. Normal cell cultures showed significantly
      higher fluorescence light emission after incubation with hepatocyte-directed ASF
      MION-rh than after incubation with MION-rh. Competition experiments of ASF-MION
      rh with galactose showed a dose-dependent decrease of calibrated fluorescence
      light emission. Cell cultures treated with CCl4 demonstrated a dose-dependent
      significant reduction of calibrated fluorescence light emission, indicating
      reduced uptake of ASF-MION-rh. Our data demonstrate that stable human hepatocyte
      cell cultures can be used to preclinically assess novel magnetopharmaceuticals.
      Different contrast agents may be directly compared to each other and may
      accelerate their preclinical design. Because the assay can be applied to cells
      from any species, it may represent an ideal test system before clinical trials of
      new cell-directed MR contrast agents.

PMID- 9626888
TI  - Small renal cell carcinoma: MRI with pathologic correlation.
AB  - The MRI features of small renal cell carcinomas (RCCs) were retrospectively
      reviewed and correlated with histology in 24 patients. MRI features on both T1-
      and T2-weighted images were classified into hypointensity, isointensity, and
      hyperintensity. Each tumor was pathologically classified into four types:
      alveolar, papillary, tubular, and cystic. These findings were correlated with MR
      signal intensities. Alveolar tumors showed hypointensity to isointensity on T1
      weighted image and isointensity to hyperintensity on T2-weighted image. In
      contrast, all papillary tumors showed hypointensity on T2-weighted image. Four of
      six tumors with hypointensity on T2-weighted image were caused by hemosiderin
      deposition, hemorrhage, and necrosis. However, there were two papillary RCCs that
      showed hypointensity on T2-weighted image despite no hemosiderin deposition and
      no hemorrhage. We conclude that papillary RCC is associated with T2-hypointense
      appearance as well as hemosiderin deposition, hemorrhage, and necrosis.

PMID- 9626889
TI  - Structure-activity relationship of macrocyclic and linear gadolinium chelates:
      investigation of transmetallation effect on the zinc-dependent metallopeptidase
      angiotensin-converting enzyme.
AB  - Transmetallation between commercially available solutions of gadolinium (Gd)
      chelates and the zinc (Zn)-dependent angiotensin-converting enzyme (ACE) was
      investigated. In vitro, the strongest inhibitions were observed for the linear Gd
      complexes, Gd diethylenetriamine pentaacetic acid (DTPA) bis-methylamide (BMA)
      (IC50 = .016 +/- .006 mmol/l) and Gd-DTPA (IC50 = .350 +/- .034 mmol/l). The two
      macrocycles Gd tetraazacyclododecane tetraacetic acid (DOTA) and Gd-HP-DO3A were
      similar and 400 times less active than Gd-DTPA-BMA. These effects were mainly due
      to the presence of free ligand for DTPA and calcium (Ca) chelate in the case of
      DTPA-BMA because the addition of Zn2+ in the same quantities suppresses their
      inhibitory effects. In vivo, these two solutions of linear Gd chelates
      significantly inhibited ACE activity (Gd-DTPA: (67 +/- 9% versus baseline; and Gd
      DTPA-BMA: 73 +/- 2% versus baseline at the clinical dose of .1 mmol/kg), whereas
      no significant effect was observed for the two macrocyclic chelates Gd-DOTA and
      Gd-HP-DO3A. Formulating the Gd chelate solution with either an excess of free
      ligand or Ca chelate (to decrease Gd3+ release) in the case of linear Gd chelate
      may have deleterious biologic consequences.

PMID- 9626890
TI  - A three-point Dixon method for water and fat separation using 2D and 3D gradient
      echo techniques.
AB  - A water and fat separation technique based on a three-point Dixon method using
      two-dimensional (2D) and three-dimensional (3D) gradient-echo sequences and a new
      phase-unwrapping approach is presented. Using velocity-compensated sequences,
      three images, with water and fat protons in phase, opposed phase, and in phase,
      were acquired in an interleaved fashion for each phase-encoding line of the
      image. A fast 2D scan permitted acquisition of images within a single breath
      hold, eliminating respiratory motion artifacts. The 3D sequence allowed coverage
      of a large region of interest with thin, contiguous slices. To correct field
      inhomogeneity effects, phase unwrapping was required. This was accomplished by
      comparing the corresponding pixels in the two water and fat in-phase images on a
      pixel-by-pixel basis. This phase-unwrapping approach is faster, more reliable,
      and requires less user interfacing than other methods. The water and fat
      separation method performed well in various parts of the body.

PMID- 9626891
TI  - MRI of the foot and ankle: diagnostic performance and patient acceptance of a
      dedicated low field MR scanner.
AB  - The objective of this study was to compare image quality and patient acceptance
      of a dedicated .2-T MR system and a 1.0-T whole body system. Forty-one
      consecutive patients referred for MRI of the foot or ankle were prospectively
      examined with a dedicated .2-T low field system and a 1.0-T whole body system.
      Images were evaluated qualitatively by two observers and quantitatively using
      signal-difference-to-noise ratios. The patients were interviewed with respect to
      positioning, examination time, noise, claustrophobia, confidence in the
      diagnosis, and willingness to repeat the examination, using a questionnaire. The
      qualitative score was significantly higher for the 1.0-T system (2.6 vs 2.2 for
      reader 1 [P = .008] and 2.6 vs 1.7 for reader 2 [P < .0001]), respectively). The
      signal-difference-to-noise ratios were also superior for the 1.0-T MR system
      (2.96 vs .88, P < .0001). However, 96% of the lesions visualized at 1.0 T were
      also detected with the low field system. Patient acceptance was significantly
      better for the 1.0-T MR scanner (48.6 vs 43.9, P = .007). Image quality of the
      dedicated low field system was inferior to the 1.0-T system using objective
      parameters, and patients did not prefer the low field system. Although only 4% of
      lesions were missed in this series, the low field MR system can only be
      recommended when funding is limited and the available space is limited.

PMID- 9626892
TI  - MRI of the cartilaginous epiphysis of the femoral head in the piglet hip after
      ischemic damage.
AB  - MRI of the cartilaginous epiphysis (CE) of piglet femoral head was performed
      after ischemic damage to study the changes in the CE found on MRI and to
      correlate these changes with histologic findings. Avascular necrosis of the
      femoral head was induced with a suture ligature in nine piglets; one piglet was
      killed postoperatively on day 3 and on weeks 1, 2, 3, 4, 6, 7, and 8 (two piglets
      were killed on week 3). MRI of the ischemic and contralateral nonischemic hip
      joints were obtained with a 60-mm field of view (low resolution MRI). Biopsy
      cores of the femoral heads were imaged with a 15-mm field of view (high
      resolution MRI) and correlated with histologic sections. The CE for all operated
      hips, except for the 3-day postoperative specimen, showed evidence of ischemic
      changes on histologic assessment; the severity of damage increased with time. The
      MRI appearance of ischemic and nonischemic CE was clearly different by 2 weeks
      after the operation. No trilaminar signal pattern was evident in the high
      resolution T2-weighted (T2W) imaging of the ischemic CE from 2 weeks after the
      operation. In the 3- to 8-week postoperative specimens, focal areas of low signal
      intensity on high resolution T1-weighted (T1W) and T2W imaging corresponded to
      the areas of chondronecrosis found on histologic assessment. The regions of high
      signal intensity on T2W imaging corresponded to the areas of chondrocyte clusters
      with increased safranin-O staining. High resolution MRI can demonstrate changes
      in the CE associated with ischemic injury and may have a role in the assessment
      of the CE and its development after ischemic injury.

PMID- 9626893
TI  - Quantification of patellar tracking using kinematic MRI.
AB  - The purpose of this study was to describe a method to quantify dynamic patellar
      tracking using kinematic MRI (KMRI). Twelve normal females and three patients
      with patellofemoral pain participated. Imaging was performed with a 1.5-T/64-MHz
      MR system using a fast spoiled gradient-recalled acquisition in the steady state
      (GRASS) pulse sequence. A nonferromagnetic positioning device permitted active,
      bilateral knee extension against resistance (15% bwt) from 45 degrees knee
      flexion to full extension. Subjects were instructed to extend their knees at a
      rate of 9 degrees per second, which allowed images to be obtained at 45 degrees,
      36 degrees, 27 degrees, 18 degrees, 9 degrees, and 0 degrees. All images were
      assessed for medial/lateral patellar displacement, patellar tilt, and sulcus
      angle using a computer-aided system. Normal patellar motion was characterized by
      medial movement from 45 degrees to 18 degrees, followed by a reversal toward
      lateral displacement from 18 degrees to full extension. The results for patellar
      tilt revealed a tendency toward decreasing lateral tilt as the knee extended.
      Sulcus angle measurements indicated that the patella was moving to a more shallow
      portion of the trochlear groove (superiorly) during extension.

PMID- 9626895
TI  - An automated measurement system for characterization of RF and gradient coil
      parameters.
AB  - A fully automated laboratory-based measurement system for characterization of
      coil system parameters is presented. This method uses an inexpensive personal
      computer (PC)-controlled stepper motor positioning system in conjunction with a
      network/spectrum analyzer and an analog-to-digital converter (A/D) board that
      allows high resolution data acquisition in an unattended manner. A graphical
      interface was created for complete control of stepper motor movement,
      measurement, and data acquisition. The system is capable of performing a wide
      range of measurements that can, either individually or combined, characterize
      radiofrequency (RF) and gradient coils used in MRI. Measurement methods, theory,
      and results for conductor and shield current distributions, mutual impedance, and
      magnetic fields are given. Comparisons with theoretical calculations are included
      to validate the accuracy and utility of the system.

PMID- 9626894
TI  - Chronic lymphocytic leukemia: changes in bone marrow composition and distribution
      assessed with quantitative MRI.
AB  - The purposes of this study were (a) to determine the prevalence of bone marrow
      abnormalities in patients with chronic lymphocytic leukemia (CLL) using
      quantitative MR assessment of axial marrow composition and peripheral marrow
      distribution; (b) to assess the agreement between both quantitative MR methods
      and compare their sensitivities to detect marrow alterations; and (c) to
      correlate MR findings with clinical and laboratory parameters. Twenty-nine
      consecutive patients with biopsy-proven CLL were investigated on a .5-T MR imager
      to determine bulk T1 relaxation times of the vertebral bone marrow and proportion
      of proximal femur surface area occupied by nonfatty marrow on coronal T1-weighted
      MR images of one hip. Of the 29 patients, 12 (41%) had abnormal increase in
      lumbar marrow T1 values (>600 msec) and 16 (55%) had increased proportion of
      surface area occupied by nonfatty marrow in the proximal femur (>+1 SD compared
      to normal values determined in sex- and age-matched healthy subjects). The
      results of both quantitative MR methods were normal in 12 patients and abnormal
      in 11 patients (agreement, 79%). Patients with alterations in peripheral marrow
      distribution had significantly higher T1 relaxation times (P = .001) than those
      with normal peripheral marrow. Patients with abnormal marrow composition or
      distribution at MRI had significantly higher blood and marrow lymphocytosis than
      patients without these features. In conclusion, the agreement between both
      quantitative MR methods suggests a parallelism between changes in axial marrow
      composition and in peripheral marrow distribution in patients with CLL. The
      limits of quantitative MRI in CLL must be kept in mind, because quantitative MR
      methods failed to detect leukemic marrow infiltration in 41% of patients.

PMID- 9626896
TI  - Placenta accreta: MRI antenatal diagnosis and surgical correlation.
AB  - We describe a case of a placenta previa accreta that was diagnosed antenatally by
      MRI with subsequent surgical confirmation. We show the advantages of ultrafast
      MRI single shot (SS) fast spin echo (FSE) techniques for accurate diagnosis with
      minimal scan time and fetal motion artifacts.

PMID- 9626897
TI  - Whole body turbo STIR MRI in unknown primary tumor detection.

PMID- 9626898
TI  - New approaches to the management of acute and chronic cardiac allograft
      rejection.
AB  - There are still many problems to be faced in the field of heart transplantation.
      Acute and chronic rejection are still the major medical obstacles. In this
      review, we describe recent research in this field undertaken in our laboratory.
      The induced intercellular adhesion molecule-1 (ICAM-1) and MHC class II antigen
      resulting from rejection can be visualized in vivo by radioimmunoscintigraphy.
      This non-invasive method is sensitive for detecting early rejection and allows
      quantitative assessment of rejection. Short-term administration of monoclonal
      antibodies to ICAM-1 and leukocyte function-associated antigen-1 (LFA-1) results
      in an indefinite acceptance of cardiac allografts by induction of antigen
      specific tolerance, as evidenced by acceptance of the secondary skin allografts.
      The characteristics and possible mechanisms of this tolerance induction are
      discussed. Immunohistopathologic features of graft coronary arteriopathy are
      shown. Adhesion molecules, cytokines, and growth factors are associated with
      intimal hyperplasia and phenotypic transformation of smooth muscle cells in the
      allograft coronary arteries. Dramatic reduction in this intimal hyperplasia was
      demonstrated by antisense gene therapy targeting cyclin-dependent kinase 2
      kinase. We hope that these investigations will contribute to the improvement of
      the management of patients who undergo heart transplantation.

PMID- 9626899
TI  - Roles of plasma platelet-activating factor acetylhydrolase in allergic,
      inflammatory, and atherosclerotic diseases.
AB  - Platelet-activating factor (PAF) mediates a variety of physiologic and pathologic
      events by activating platelets, neutrophils, monocytes, macrophages, and smooth
      muscle cells. A strongly oxidizing environment induces fragmentation of the
      polyunsaturated fatty acids of membrane phospholipids, and the resulting oxidized
      phospholipids are structurally similar to PAF and mimic its biologic actions. The
      effects of PAF and oxidized phospholipids are abolished by hydrolysis of the sn-2
      residue, a reaction catalyzed by PAF acetylhydrolase. Plasma and intracellular
      forms of PAF acetylhydrolase have been purified and characterized. The plasma
      form binds with high affinity to lipoproteins in plasma. Furthermore, changes in
      the activity of this enzyme are associated with various human diseases and animal
      models of human pathology, suggesting that it may play important roles in their
      pathogenesis. Studies that have defined the properties of this enzyme and its
      roles in physiologic and pathologic processes are reviewed. Such studies have
      provided insight into the functions of PAF and oxidized phospholipids as well as
      into the etiology of allergic, inflammatory, and atherosclerotic diseases.

PMID- 9626900
TI  - Relative usefulness of measures of heart rate variability and neuroendocrine
      activity as indicators of autonomic nervous abnormality in patients with left
      ventricular dysfunction.
AB  - The aim of the study was to assess the relationship between changes in heart rate
      variability (HRV) and parameters of neuroendocrine activation in patients with
      various levels of left ventricular dysfunction. Measurements of HRV, plasma
      norepinephrine (PNE), and plasma atrial natriuretic peptide (ANP) were performed
      in 17 age- and gender-matched control subjects (group C) and in 39 patients with
      ischemic heart disease or cardiomyopathy who were subdivided into 3 equal groups
      according to their left ventricular ejection fraction: group N (normal); group M
      (mildly impaired); and group S (severely impaired). Spectral analysis of HRV
      (from 10-min electrocardiograms) was analyzed by the method of coarse-graining
      spectral analysis. PNE and ANP were significantly elevated in group S only
      (p<0.05). Log low-frequency power and log total power for group M were
      significantly lower than for group N (p<0.05). Log high-frequency power was
      significantly lower for group M than for group C (p<0.05). Thus, assessment of
      changes in HRV, which were observed earlier in the progress of left ventricular
      dysfunction than changes in neuroendocrine factors, may be a useful non-invasive
      method for the early detection of autonomic abnormality in patients with left
      ventricular dysfunction.

PMID- 9626901
TI  - Efficacy of oral magnesium administration on decreased exercise tolerance in a
      state of chronic sleep deprivation.
AB  - We have previously reported that chronic sleep deprivation causes a deficiency of
      intracellular magnesium (Mg) and decreased exercise tolerance. The aim of this
      study was to clarify whether oral administration of Mg could be effective in
      restoring the exercise tolerance that is decreased by chronic sleep deprivation.
      A bicycle ergometer cardiopulmonary exercise test was performed by 16 healthy
      volunteers (mean age 21.9 years). They were divided into 2 groups: 8 received
      doses of 100 mg of Mg orally per day for 1 month (Mg group) and the remaining 8
      received no Mg and served as the control group. The study conditions were
      designed as follows: (1) the usual state (good sleep); and (2) the sleep-deprived
      state (sleeping time up to 60% less than the usual state for 1 month). The ratio
      of intracellular Mg content of the sleep-deprived state to the usual sleep state
      was significantly higher in the Mg group (p<0.05) than the untreated control
      group. There was no difference between the sleep-deprived state and the usual
      state with regard to anaerobic threshold and peak oxygen uptake in the Mg group,
      whereas both of these decreased in the sleep-deprived state in the control group.
      These results indicate that decreased exercise tolerance observed in the sleep
      deprived state could be improved by oral Mg administration.

PMID- 9626902
TI  - The usefulness of Holter monitoring in selecting pharmacologic therapy for
      patients with sustained monomorphic ventricular tachycardia: studies in patients
      in whom no effective pharmacologic therapy could be determined by
      electrophysiologic study.
AB  - The usefulness of Holter monitoring (HM) in selecting pharmacologic therapy for
      patients with sustained monomorphic ventricular tachycardia (VT) was evaluated in
      patients in whom no effective pharmacologic therapy could be determined in an
      electrophysiologic study (EPS). The study population consisted of 49 consecutive
      patients with sustained VT who were receiving long-term pharmacologic therapy
      despite the fact that no pharmacologic therapy had been found to be effective in
      the EPS. The efficacy of the pharmacologic therapies was assessed by HM. A
      reduction in frequent (10/h) premature ventricular contractions (PVCs) was used
      as an index of treatment efficacy, with therapies achieving substantial PVC
      suppression (>70% of all PVCs) being considered to be effective (HM effective
      group). When no therapy was found to be effective when assessed by HM, a drug
      with any other beneficial effect, eg, reduction in VT rate, was chosen (HM
      ineffective group). VT recurrence and survival were compared between groups.
      During the follow-up period of 31+/-28 months, VT recurrence was observed in a
      total of 25/49 patients: 3/17 patients in the HM effective group, in 18/25 in the
      HM ineffective group, and in 4/7 in the HM undetermined group (p=0.0487). Sudden
      cardiac death occurred in a total 7/49 patients: 2/17 patients in the HM
      effective group, 4/25 patients in the HM ineffective group, and 1/7 patient in
      the HM undetermined group (p=0.2828). Among patients in whom no effective therapy
      could be determined by EPS, the VT recurrence rate was significantly lower in the
      group in whom treatment was effective as assessed by HM than among those in whom
      treatment was assessed by HM to be ineffective. Sudden cardiac death rate was
      also lowest in the HM effective group, although the difference was not
      statistically significant. HM assessment was considered useful in selection of
      pharmacologic therapy for patients in whom no effective therapy could be
      determined in the EPS.

PMID- 9626904
TI  - Angiographic evaluation of culprit lesions in acute coronary syndrome: relation
      to the original site on previous coronary angiography.
AB  - Culprit lesions in acute coronary syndrome [acute myocardial infarction (AMI) and
      unstable angina pectoris (UAP)] were examined angiographically in 222 patients
      who had previously undergone coronary angiography (CAG). The observation period
      lasted 5 years after primary CAG in medically treated patients (group M, 127
      cases) and after final follow-up CAG in patients treated by percutaneous
      transluminal coronary angioplasty (PTCA) (group B, 95 cases). There were 33 AMIs,
      including 5 deaths (22/127, 17.3%, in group M vs 11/95, 11.6%, in group B;
      p<0.01) and 189 UAPs (105/127, 82.7%, in group M vs 84/95, 88.4%, in group B;
      NS). High-grade stenoses (>75%) were found in 76 (59.8%) patients in group M, of
      which 41 lesions (54%) resulted in acute coronary syndromes (ACSs). In group M,
      ACSs resulted from insignificant stenosis (< or =50%) in 67 (53%) patients and
      from significant stenosis (>50%) in 60 (47%) patients. In group B, ACSs resulted
      from insignificant stenosis in 78 (82%) patients and from significant stenosis in
      17 (18%) patients. Out of 95 PTCA sites, high-grade restenosis occurred in 3
      lesions and ACSs (2 AMI, 14 UAP) in 16 (16.8%). We conclude that ACSs are more
      likely to develop from insignificant lesions than from significant lesions. High
      grade stenoses are prone to become occlusive lesions and PTCA reduces this
      potential risk. Most target sites of PTCA that escaped restenosis were stable in
      the long term.

PMID- 9626903
TI  - Preventive effects of angiotensin-converting enzyme inhibitors on nitrate
      tolerance during continuous transdermal application of nitroglycerin in patients
      with chronic heart failure.
AB  - This study was designed to investigate the effect of angiotensin-converting
      enzyme (ACE) inhibitors with and without a sulfhydryl group on intracellular
      production of cGMP, forearm blood flow, and neurohormonal factors during
      continuous transdermal application of nitroglycerin in patients with chronic
      heart failure. Platelet cGMP level and forearm blood flow were measured before
      and 5 min after sublingual administration of nitroglycerin (NTG) in 20 patients
      with chronic heart failure during the following 4 phases: (1) baseline phase; (2)
      NTG phase (1 week after NTG tape 10 mg/day); (3) CPT phase (1 week after both
      captopril 37.5 mg/day and NTG tape 10 mg/day); and (4) ENL phase (1 week after
      both enalapril 5 mg/day and NTG tape 10 mg/day). The platelet GMP level before
      sublingual NTG and forearm blood flow were significantly higher during the 3
      phases with NTG tape than during the control phase. The percent increases in
      platelet cGMP level and forearm blood flow after sublingual NTG were
      significantly lower during the NTG phase than during the baseline phase. In
      contrast, concomitant application of ACE inhibitors maintained the percent
      increase in platelet cGMP level and forearm blood flow. These results indicate
      that concomitant therapy with ACE inhibitors may be helpful in preventing the
      attenuation of intracellular cGMP production in patients with chronic heart
      failure during continuous transdermal application of NTG.

PMID- 9626905
TI  - Myocardial uptake of iodine-125-labeled 15-(p-iodophenyl)-3-(R,S)-methyl
      pentadecanoic acid is decreased in chronic diabetic rats with changes in
      subcellular distribution.
AB  - Iodine-123-labeled 15-(p-iodophenyl)-3-(R,S)-methyl pentadecanoic acid (123I
      BMIPP) is widely used to detect myocardial metabolic changes, but the preferred
      energy substrates in the myocardium would be expected to be altered in the
      presence of metabolic disorders such as diabetes mellitus (DM). We investigated
      the metabolism of branched-chain fatty acids in the myocardium of rats with DM.
      Streptozotocin-induced DM rats were examined 48 h (acute; AD) and 6 weeks
      (chronic; CD) after injection of streptozotocin. Hearts were excised 15 min or 60
      min after injection of 0.185 MBq of 125I-BMIPP, followed by homogenization in an
      EDTA-Tris buffer. The homogenates were subjected to differential centrifugation
      to obtain the mitochondrial (MF) and cytoplasmic (CF) fractions. Myocardial 125I
      uptake tended to increase in the AD group, but the change was not significant.
      Myocardial 125I uptake at 15 min was significantly lower in the CD group than in
      the control group, even in the insulin-treated rats [control (CC), 4.4+/-0.4; not
      treated (CDN), 3.3+/-0.5; insulin-treated (CDI), 3.4+/-0.4 x 10(4) cpm/g, p<0.05
      in each case]. The 125I count value corrected for the blood count (counts/min
      (cpm) per g of protein divided by blood cpm) in the MF decreased by 40% at 60 min
      in the CC group, but increased by 60% in the CDN group. The results of the
      present study suggest that the myocardial uptake of branched-chain fatty acids is
      decreased in rats with chronic diabetes, probably as a result of mitochondrial
      dysfunction.

PMID- 9626907
TI  - Primary pulmonary artery sarcoma.
AB  - A 66-year-old woman with a history of mitral valve replacement with a Starr
      Edwards ball valve 25 years ago was treated for refractory heart failure but died
      of right heart failure. At autopsy, primary pulmonary artery sarcoma was found in
      the right ventricular outflow tract, main pulmonary trunk, and bilateral
      pulmonary artery, and had invaded the aortic arch. The pathohistologic diagnosis
      was osteosarcoma. Echocardiography, chest computed tomography and right
      ventriculography performed 1 year before death did not reveal the presence of a
      tumor in the pulmonary artery. The history of this patient shows that primary
      pulmonary artery sarcoma grows rapidly, with, in this case, the patient dying
      within 1 year of its appearance.

PMID- 9626906
TI  - Influence of chronic nitric oxide inhibition of coronary blood flow regulation: a
      study of the role of endogenous adenosine in anesthetized, open-chested dogs.
AB  - The effect of chronic inhibition of endothelium-derived nitric oxide (NO)
      synthesis on the regulation of coronary blood flow (CBF) is yet to be elucidated.
      A chronic canine model of inhibited NO synthesis was created and the role of
      adenosine in the regulation of coronary blood flow in this model was examined.
      Dogs were fed a diet supplemented with 40 mg/kg per day N(G)-nitro-L-arginine
      methyl ester (L-NAME group, n=8) or a regular diet without L-NAME supplementation
      (control group, n=8) for 4 weeks. The experiments were performed in an
      anesthetized, open-chest state and the results were compared in the L-NAME and
      control groups. Chronic L-NAME treatment significantly increased arterial
      pressure. Neither basal CBF in the left anterior descending artery nor heart rate
      differed between the L-NAME and control groups. In the L-NAME group, the response
      of CBF to intracoronary acetylcholine and adenosine was blunted, but that to
      glyceryl trinitrate was not. In addition, myocardial reactive hyperemia following
      20 sec coronary occlusion was blunted in the L-NAME group. During atrial pacing
      at a rate 60 beats/min faster than the sinus rate, CBF increased to a similar
      degree in the L-NAME and control groups, and systolic wall thickening (SWT)
      changed similarly in both groups. Intracoronary 8-phenyltheophylline (8-PT), an
      adenosine receptor blocker, decreased basal CBF in the L-NAME group but not in
      the control group. In the L-NAME group, pacing-induced increase in CBF was
      abolished and SWT deteriorated after 8-PT administration. Basal myocardial
      adenosine release was significantly increased in the L-NAME group compared with
      the control group. It is concluded that in anesthetized, open-chest dogs with
      chronic inhibition of NO synthesis, adenosine may play a compensatory role in the
      regulation of coronary blood flow, as concomitant blockade of adenosine causes
      deterioration of coronary circulation and cardiac function.

PMID- 9626908
TI  - Saphenous vein graft shrinkage as a mechanism of stenosis soon after bypass
      surgery.
AB  - A 63-year-old man with left main coronary artery disease underwent aortocoronary
      bypass surgery using saphenous vein grafts. Less than 1 month later, severe
      narrowing occurred in the mid-portion of the vein graft to the left anterior
      descending coronary artery. Preintervention intravascular ultrasonography
      revealed prominent vein graft shrinkage. Percutaneous transluminal angioplasty
      failed because the stenotic lesion could not be dilated, even by high-pressure
      balloon inflation. Saphenous vein graft shrinkage appears to be one of the
      mechanisms of early saphenous vein graft stenosis, and balloon angioplasty to the
      vein graft stenosis with prominent shrinkage may be of only limited value.

PMID- 9626909
TI  - An early systolic sound associated with midventricular obstruction in a patient
      with hypertrophic cardiomyopathy.
AB  - A 57-year-old woman was admitted for examination because of chest discomfort.
      Transthoracic echocardiography was performed and she was diagnosed as having
      hypertrophic cardiomyopathy. An echocardiogram also revealed that she had
      midventricular obstruction with a pressure gradient of 125 mmHg determined by
      Doppler echocardiography. A phonocardiogram showed an early systolic sound and
      the beginning of the sound coincided with the time of septal-posterior wall
      contact. In addition, the timing also corresponded to the sudden obstruction of
      blood flow in the region of the midventricular narrowing. Furthermore, this sound
      markedly decreased with the reduction in pressure gradient caused by cibenzoline
      treatment. Thus, it was concluded that the early systolic sound was associated
      with midventricular obstruction and produced by a rapid deceleration of the
      interventricular flow caused by midventricular obstruction.

PMID- 9626911
TI  - Traditional remedies and the "test of time".

PMID- 9626910
TI  - Hepatitis C virus infection and heart diseases: a multicenter study in Japan.
AB  - As a collaborative research project of the Committees for the Study of Idiopathic
      Cardiomyopathy, a questionnaire was sent out to 19 medical institutions in Japan
      in order to examine the possible association between hepatitis C virus (HCV)
      infection and cardiomyopathies. Hepatitis C virus antibody was found in 74 of 697
      patients (10.6%) with hypertrophic cardiomyopathy (mean age, 57.7 years) and in
      42 of 663 patients (6.3%) with dilated cardiomyopathy (mean age, 56.5 years);
      these prevalences were significantly higher than that found in volunteer blood
      donors in Japan (2.4%, 50-59 years of age, each p<0.0001). The prevalence was
      significantly higher in patients suffering from hypertrophic cardiomyopathy as
      opposed to those with dilated cardiomyopathy (p<0.01). The presence of HCV
      antibody was detected in 650 of 11,967 patients (5.4%) patients seeking care in 5
      academic hospitals. Various cardiac abnormalities were found among these
      patients, arrhythmias being the most frequent. These observations suggest that
      HCV infection is an important cause of a variety of otherwise unexplained heart
      diseases.

PMID- 9626912
TI  - Use and abuse of placebo in phase III trials.

PMID- 9626913
TI  - Single-dose dextropropoxyphene in post-operative pain: a quantitative systematic
      review.
AB  - OBJECTIVE: To determine the analgesic efficacy and adverse effects of single-dose
      oral dextropropoxyphene alone and in combination with paracetamol for moderate to
      severe post-operative pain. METHODS: Published reports were identified from a
      variety of electronic databases including MEDLINE, Biological Abstracts, EMBASE,
      the Cochrane Library and the Oxford Pain Relief Database. Additional studies were
      identified from the reference lists of retrieved reports. Summed pain intensity
      and pain relief data were extracted and converted into dichotomous information to
      yield the number of patients with at least 50% pain relief. This was used to
      calculate the relative benefit and number-needed-to-treat for one patient to
      achieve at least 50% pain relief. Six reports (440 patients) compared
      dextropropoxyphene with placebo and five (963 patients) compared
      dextropropoxyphene plus paracetamol 650 mg with placebo. RESULTS: For a single
      dose of dextropropoxyphene 65 mg in post-operative pain the number-needed-to
      treat for at least 50% pain relief was 7.7 (95% confidence interval 4.6 to 22)
      when compared with placebo over 4-6 h. For the equivalent dose of
      dextropropoxyphene in combination with paracetamol 650 mg the number-needed-to
      treat was 4.4 (3.5 to 5.6) when compared with placebo. Pooled data showed
      increased incidence of central nervous system adverse effects for
      dextropropoxyphene plus paracetamol when compared with placebo. A rank order of
      single-dose analgesic effectiveness in post-operative pain of moderate to severe
      intensity obtained from similar systematic reviews is presented. CONCLUSION:
      Dextropropoxyphene 65 mg plus paracetamol 650 mg has a similar analgesic efficacy
      to that of tramadol 100 mg but with a lower incidence of adverse effects.
      Ibuprofen 400 mg has a lower (better) number-needed-to-treat than both
      dextropropoxyphene 65 mg plus paracetamol 650 mg and tramadol 100 mg.

PMID- 9626914
TI  - Drug utilization 90%--a simple method for assessing the quality of drug
      prescribing.
AB  - OBJECTIVES: To describe a simple method for assessing the quality of drug
      prescribing. METHODS: We tested the idea that the number of drugs accounting for
      90% of drug use--drug utilization 90% (DU90%)--may serve as an indicator of the
      quality of drug prescribing. We ranked the drugs by volume of defined daily doses
      (DDD) and determined how many drugs accounted for the DU90% segment. We also
      compared this segment with the pharmacotherapeutic guidelines issued by the
      Regional (local) Drug Committee to determine the adherence to its recommendations
      (index of adherence). The cost per DDD within the DU90% segment and for the
      remaining 10% was also calculated. The utilization of drugs based on
      prescriptions purchased during April 1995 was determined for 24 primary health
      care (PHC) centres in southwestern Stockholm. RESULTS: The number of different
      products, defined as all products marketed under a single brand name within an
      ATC (anatomic therapeutic chemical) category, in the DU90% segment varied twofold
      (81-164) between the 24 PHC centres. Differences in the number of GPs per PHC
      centre accounted for a third of this variation. The compliance with the Drug
      Committee recommendations varied between 54% and 78%. There was no relationship
      between the number of products accounting for the DU90% segment and the adherence
      to local prescription guidelines, i.e. prescribing more products did not increase
      the adherence. The costs for the DU90% drugs varied from 2.26 SEK/DDD in one PHC
      centre to 3.75 in another one, with an average cost of 2.87 SEK/DDD, while for
      the remaining 10% it was the double (6:54 SEK/DDD). In all, the DU90% drugs made
      up 80.8% of the total cost as compared with 19.2% for the remaining 10%. In the
      DU90% segment, there was no clear relationship between adherence to the
      guidelines and the cost/DDD, i.e. following the evidence-based guidelines
      appeared to provide a higher quality of prescribing rather than cheaper
      prescribing. CONCLUSIONS: The DU90% is an inexpensive, flexible, and simple
      method for assessing the quality of drug prescribing in routine health care. The
      number of products in the DU90% segment and adherence to prescription guidelines
      may serve as general quality indicators. The method may be adapted to provide
      comparative data between PHC centres, hospitals, regions etc. that may be cross
      sectional and longitudinal. Other quality criteria, specific for each class of
      drugs, should complement these general indicators.

PMID- 9626915
TI  - Drug use in Estonia in 1994-1995: a follow-up from 1989 and comparison with two
      Nordic countries.
AB  - OBJECTIVE: To determine the patterns of drug use in Estonia for the years 1989
      and 1994 1995, i.e. for the years before and after the pharmaceutical services in
      the country changed from a state monopoly to a competitive market. METHODS: The
      wholesale data from Estonia and the defined daily doses methodology were used.
      For comparison, national statistics on medicines from Finland and Sweden for the
      years 1994-1995 are shown. RESULTS: The general sales of drugs in Estonia
      decreased almost twofold in all major pharmacological groups from 1989 to 1994
      and subsequently increased by 10%-30% in 1995. Substantial differences in
      patterns of drug use between Estonia and the two Nordic countries were observed.
      The amount of prescription-only medicines used in Estonia was approximately 25%
      of that used in Finland and Sweden. The amount of over-the-counter drugs used was
      61% of that used in Finland and 58% of that used in Sweden. In the drug use
      patterns in Estonia, some common trends can be noted: (1) persistent traditions,
      such as the low use of diuretics, beta-blockers, antithrombotics and inhalant
      anti-asthmatic drugs; (2) changes in prescription preferences--central anti
      adrenergic drugs, pyrazolones, aminoglycosides and barbiturates are being
      replaced by calcium channel blockers and angiotensin-converting-enzyme
      inhibitors, propionic acid derivatives, cephalosporins and benzodiazepines,
      respectively; (3) rapidly increasing use of drugs not prescribed in the 1980s,
      such as hormonal contraceptives, opioids and antiulcer drugs, which strongly
      improves the quality of pharmacotherapy in Estonia. CONCLUSION: The general
      trends in Estonia and the two Nordic countries are similar--the use of newer and
      more effective drugs is increasing and that of older ones decreasing. The changes
      are more rapid in Estonia than in Finland and Sweden, but, because of a short
      observation period, the use of newer drugs not yet prevailing. The international
      differences in drug utilization observed in this study may possibly be related
      mainly to the prescription preferences (e.g. therapeutic traditions) and less
      dependent on the respective health care systems (e.g. reimbursement schemes) and
      economic state of the country.

PMID- 9626916
TI  - Efficacy and tolerability of orlistat in the treatment of obesity: a 6-month dose
      ranging study. Orlistat Dose-Ranging Study Group.
AB  - OBJECTIVE: To determine the weight-reducing efficacy of orlistat, a novel
      gastrointestinal lipase inhibitor, and to define the optimal dosage regimen and
      establish the tolerability of the drug when used for a 6-month treatment period.
      METHODS: The study was a multicentre randomised, double-blind, parallel group in
      design and involved 676 obese male and female subjects aged at least 18 years
      with a body mass index between 28 and 43 kg x m(-2) Following a 5-week placebo
      run-in period, subjects were randomised to receive orlistat 30 mg, 60 mg, 120 mg,
      240 mg or matching placebo three times a day (tid) for 24 weeks during meals.
      Patients were maintained on a mildly hypocaloric diet throughout the study
      period. The primary efficacy parameter was body weight change over time. RESULTS:
      Orlistat resulted in a significantly greater mean loss of body weight than
      observed in the placebo group. In absolute terms, mean weight loss was greatest
      in the 120 mg group (9.8%). More orlistat- than placebo-treated patients lost >
      10% of initial body weight (37% of the 120 mg group vs 19% of the placebo group).
      Orlistat was well tolerated. Predictably, in view of its known pharmacological
      effects, more orlistat-treated patients experienced gastrointestinal events. Mean
      levels of vitamins A, D and E, and beta-carotene remained within the clinical
      reference ranges in all treatment groups and rarely required supplementation.
      After 24 weeks, plasma concentrations of orlistat were either non-measurable or
      detected at the assay's limit of quantitation. CONCLUSION: Orlistat treatment
      results in a dose-dependent reduction in body weight in obese subjects and is
      well tolerated. Orlistat 120 mg tid represents the optimal dosage regimen.

PMID- 9626917
TI  - Desmin (a low molecular weight dermatan sulphate) versus heparin in the treatment
      of patients with deep venous thrombosis.
AB  - OBJECTIVE: There is theoretical and experimental evidence which indicates that
      Desmin, a low molecular weight dermatan sulphate, could be an attractive
      alternative to heparin in the treatment of deep venous thrombosis (DVT). The
      present study compares both compounds in patients with established DVT. METHODS:
      Seventeen consecutive patients admitted with DVT were included in a randomised
      open study comparing continuous intravenous administration of Desmin and
      continuous intravenous administration of heparin. Clinical, laboratory and
      imaging parameters were used to assess the efficacy and safety of both
      treatments. RESULTS: The results of the coagulation tests confirmed the published
      data on the antithrombotic profile of Desmin. A trend towards better biochemical
      tolerance was observed with Desmin. Repeated echo duplex examinations of the deep
      venous system could not document further thrombus extension in any patient. Pre-
      and post-treatment phlebographic Marder scores showed a non-significant trend
      towards superior efficacy of Desmin. Overall, the results regarding efficacy and
      safety were not significantly different in the two groups. CONCLUSION: Desmin can
      be safely studied as an alternative to conventional anticoagulation in the
      treatment of DVT.

PMID- 9626918
TI  - The extrapulmonary effects of increasing doses of formoterol in patients with
      asthma.
AB  - OBJECTIVE: To assess the cardiovascular and metabolic responses to increasing
      doses of formoterol administered from a dry powder inhaler. METHODS: Twenty
      patients with mild to moderate asthma were given 12, 24, 48 and 96 microg of
      formoterol or a matched placebo on separate days. The doses were administered
      using a randomised, cross-over, double-blind design. The effects on heart rate,
      blood pressure, electromechanical systole (QS2I), the electrocardiographic QTc
      interval, plasma potassium (K); blood glucose and FEV1 were assessed prior to,
      and for 9 h following each dose. RESULTS: There was no difference between the
      maximum effects of formoterol 12 microg and placebo; the 24 microg dose
      significantly decreased plasma K (-0.2 mmol x l(-1)) and increased blood glucose
      (1.8 mmol x l(-1)) compared to placebo. The two highest doses affected most of
      the variables with the 96 microg dose being significantly different from placebo
      for all indices, heart rate (9 beats x min(-1)), systol BP (4 mmHg), diastolic BP
      (-3 mmHg), QS2I (-11 ms), QTc (17 ms), plasma K (-0.5 mmol x l(-1)) and blood
      glucose (2.6 mmol x l(-1)). All doses of formoterol increased FEV1. CONCLUSION:
      Although there were dose-dependent effects on the extrapulmonary measurements,
      only the effects at the highest dose may be of clinical significance.

PMID- 9626919
TI  - Interaction between timolol eyedrops and oral nicardipine or oral diltiazem in
      healthy Japanese subjects.
AB  - OBJECTIVE: Timolol is widely used for the topical therapy of glaucoma. Adverse
      cardiovascular effects include slowing of the heart rate and weakening of
      myocardial contractility. We investigated pharmacodynamic interactions with
      respect to cardiovascular and ocular responses between timolol ophthalmic
      solution and either nicardipine, which does not directly inhibit cardiac
      conduction, or diltiazem, which does. METHODS: Two studies utilized a randomized,
      double-blind, Latin-square, placebo-controlled design involving four separate
      treatments given at least 1 week apart. Eight healthy male Japanese volunteers
      received a single drop of 0.5% timolol or artificial tears in each eye with or
      without a single oral dose of nicardipine (40 mg), and with or without a single
      oral dose of diltiazem (60 mg). Subjects exercised on a bicycle ergometer before
      and 1.5 and 3 h after dosing. At these times, heart rate and blood pressure were
      measured at rest and after exercise. The intraocular pressure was measured at
      rest. RESULTS: One drop of 0.5% timolol per eye significantly reduced the
      exercise-induced increase in heart rate and blood pressure, and intraocular
      pressure at rest. The timolol ophthalmic solution suppressed the reflex
      sympathetic cardiac stimulation that resulted from the primarily vasodilative
      action of nicardipine. No additional reduction in heart rate occurred when the
      ophthalmic timolol solution was administered in conjunction with diltiazem. The
      concomitant use of timolol and nicardipine or diltiazem did not induce an
      additional reduction in intraocular pressure. Oral nicardipine or diltiazem did
      not reduce intraocular pressure. Care should be taken when using topical timolol
      in patients with cardiovascular or respiratory diseases.

PMID- 9626920
TI  - Effect of rifampicin on the pharmacokinetics of itraconazole in normal volunteers
      and AIDS patients.
AB  - OBJECTIVE: To investigate the effects of rifampicin on the pharmacokinetics of
      itraconazole in humans. METHODS: Our study was conducted with six healthy normal
      volunteers and three AIDS patients. All subjects received a 200 mg single dose of
      oral itraconazole on day 1 and day 15 and 600 mg of oral rifampicin once daily
      from day 2 to day 15. Itraconazole pharmacokinetics studies were carried out on
      day 1 (phase 1) and day 15 (phase 2). The limit of detection for itraconazole
      concentration was 16 ng x ml(-1). RESULTS: Concentrations itraconazole were
      higher when it was administered alone than when it was administered with
      rifampicin. Coadministration of rifampicin resulted in undetectable levels of
      itraconazole in all subjects except one normal volunteer. The mean AUC0-24 was
      3.28 vs 0.39 microg x h x ml(-1) in phase 1 and 2, respectively, in healthy
      normal volunteers. Therefore, the estimated minimum decrease of the mean AUC0-24
      of itraconazole in phase 2 was approximately 88% compared with phase 1. The mean
      AUC0-24 was 1.07 vs 0.38 microg x h x ml(-1) in phase 1 and 2, respectively, in
      AIDS patients. Therefore, the estimated minimum decrease of the mean AUC0-24 of
      itraconazole in phase 2 was approximately 64% compared with phase 1. CONCLUSION:
      Rifampicin has a very strong inducing effect on the metabolism of itraconazole,
      so that these two drugs should not be administered concomitantly.

PMID- 9626921
TI  - Effect of omeprazole on the pharmacokinetics of itraconazole.
AB  - OBJECTIVE: To investigate the effect of omeprazole on the pharmacokinetics of
      itraconazole. METHODS: Eleven healthy volunteers received a single dose of oral
      itraconazole (200 mg) on days 1 and 15 and oral omeprazole (40 mg) once daily
      from day 2 to day 15. Itraconazole pharmacokinetics were studied on days 1 and
      15. RESULTS: Concentrations of itraconazole were higher when it was taken alone
      than when it was taken with omeprazole. With concomitant omeprazole treatment,
      the mean AUC0-24 and Cmax of itraconazole were significantly reduced by 64% and
      66%, respectively. CONCLUSION: Omeprazole affects itraconazole kinetics, leading
      to a reduction in bioavailability and Cmax. These two drugs should not be used
      together.

PMID- 9626922
TI  - Effect of itraconazole on the pharmacokinetics and pharmacodynamics of zolpidem.
AB  - OBJECTIVE: Zolpidem is a short-acting imidazopyridine hypnotic which is
      biotransformed in humans mainly by CYP3A4. Itraconazole strongly interacts with
      many substrates of CYP3A4 such as midazolam and triazolam. In this study, the
      effect of itraconazole on the pharmacokinetics and pharmacodynamics of zolpidem
      was investigated to uncover a possible clinically significant interaction.
      METHODS: In a randomized cross-over study with two phases, ten healthy volunteers
      took either 200 mg itraconazole or placebo once daily for 4 days. A single oral
      dose of 10 mg zolpidem was given on day 4. Plasma drug concentrations were
      measured up to 17 h and effects of zolpidem up to 9 h after the ingestion of
      zolpidem. RESULTS: Itraconazole had no marked effects on the pharmacokinetics of
      zolpidem; the total area under the plasma zolpidem concentration-time curve (AUC0
      infinity) was 34% larger during the itraconazole phase (759 ng x h x ml(-1)) than
      during the placebo phase (567 ng x h x ml(-1)). Exophoria of the eyes by the
      Maddox wing test was significantly increased by itraconazole, but the results of
      the digit symbol substitution test, critical flicker fusion test, postural sway
      tests and the visual analogue scale tests for subjective drowsiness and overall
      drug effect did not differ between the phases. CONCLUSION: The pharmacokinetics
      and pharmacodynamics of zolpidem were not remarkably affected by itraconazole in
      healthy volunteers. Therefore, unlike triazolam, for example, zolpidem can be
      used in normal or nearly normal doses together with itraconazole and probably
      also with other CYP3A4 inhibitors.

PMID- 9626923
TI  - Serum concentrations of clozapine and N-desmethylclozapine are unaffected by the
      potent CYP3A4 inhibitor itraconazole.
AB  - OBJECTIVE: We studied a possible pharmacokinetic interaction between clozapine
      and itraconazole, a potent CYP3A4 inhibitor. METHODS: A double-blind randomized
      study design was used. Seven schizophrenic inpatients volunteered to receive, in
      addition to their previous drug regimen, either 200 mg itraconazole or placebo
      for 7 days. For the next 7 days, itraconazole was changed to placebo and vice
      versa. Serum concentrations of clozapine and its main metabolite
      desmethylclozapine were measured on days 0, 3, 7, 10 and 14. RESULTS: Concomitant
      administration of itraconazole had no significant effect on serum concentrations
      of clozapine or desmethylclozapine. CONCLUSION: CYP3A4 seems to be of minor
      importance in clozapine metabolism in humans. Itraconazole, and probably also
      other inhibitors of CYP3A4, can be used concomitantly with clozapine.

PMID- 9626924
TI  - Bayesian pharmacokinetic estimation of vinorelbine in non-small-cell lung cancer
      patients.
AB  - OBJECTIVE: To develop a population pharmacokinetics of vinorelbine in a
      population of non-small-cell lung cancer (NSCLC) patients using a Bayesian
      estimation in order to calculate for any further patient, individual
      pharmacokinetic parameters from few blood samples. METHODS: Vinorelbine was given
      by a 15-min infusion (30 mg x m(-2)) to eight patients with NSCLC. Its serum
      concentration was determined by HPLC and its pharmacokinetics was described by a
      three-compartment open model with elimination from the central compartment.
      Volume of the central compartment (V1) and rate constants (k10, k12, k21, k13,
      k31) were selected as population pharmacokinetic parameters and computed by non
      linear regression (two-step approach) from 14 to 18 concentration measurements
      per course. Subsequently, these parameters were used by the Bayesian estimator to
      calculate individual pharmacokinetics from only 2 or 3 measured concentrations.
      RESULTS: The population mean values (CV%) of V1, k10, k12, k21, k13, k31, CL,
      t1/2gamma were respectively 21 l (55%), 3.2 h(-1) (29%), 7.7 h(-1) (74%), 1.3 h(
      1) (67%), 4.7 h(-1) (53%), 0.04 h(-1) (20%), 57 l x h(-1) (31%) and 43 h (36%).
      The comparison of results obtained from the Bayesian estimator and from the three
      compartment model showed that CL and t1/2gamma were well predicted (relative
      deviation: +/- 12 to 22%) by the Bayesian method using only two blood samples.
      CONCLUSION: We demonstrated that Bayesian estimation allows, at minimal cost and
      minimal disturbance for the patient, the determination of several vinorelbine
      pharmacokinetic parameters and therefore dose adaptation from as few as two drug
      concentrations, measured at 6 h and 24 h after infusion.

PMID- 9626925
TI  - Prediction of drug-drug interactions of zonisamide metabolism in humans from in
      vitro data.
AB  - OBJECTIVE: The purposes of this study were to identify the P450 enzyme (CYP)
      responsible for zonisamide metabolism in humans by using expressed human CYPs and
      to predict drug interaction of zonisamide in vivo from in vitro data. METHODS:
      Ten expressed human CYPs and human liver microsomes were used in the experiments
      for the identification of enzymes responsible for zonisamide metabolism and for
      the prediction of drug-drug interactions of zonisamide metabolism in humans from
      in vitro data, respectively. Two-sulfamoylacetyl phenol, a reductive metabolite
      of zonisamide, was measured by the HPLC method. RESULTS: From the experiments
      using ten expressed human CYPs, CYP2C19, CYP3A4 and CYP3A5 were shown to be
      capable of catalyzing zonisamide reduction. However, an intrinsic clearance,
      Vmax/kM, of CYP3A4 was much higher than those of CYP2C19 and CYP3A5. From the
      point of view of enzyme amount in human liver CYPs isoform and their intrinsic
      clearance, it was suggested that CYP3A4 is mainly responsible for zonisamide
      metabolism in human CYPs. Zonisamide metabolism in human liver microsomes was
      markedly inhibited by cyclosporin A, dihydroergotamine, ketoconazole,
      itraconazole, miconazole and triazolam. We estimated the possibility and degree
      of change of zonisamide clearance in vivo in clinical dose range from in vitro
      inhibition constant of other drugs against zonisamide metabolism (Ki) and unbound
      inhibitor concentration in blood (Iu) in clinical usage. Clearance of zonisamide
      was maximally estimated to decrease by 31%, 23% and 17% of the clearance without
      inhibitors i.e. ketoconazole, cyclospolin A and miconazole, respectively.
      Fluconazole and carbamazepine are estimated to decrease by 5-6% of the clearance
      of zonisamide. On the other hand, there may be lack of interaction of zonisamide
      metabolism by dihydroergotamine, itraconazole and triazolam in clinical dose
      range. CONCLUSION: We demonstrated that: (1) zonisamide is metabolized by
      recombinant CYP3A4, CYP2C19 and CYP3A5, (2) the metabolism is inhibited to a
      variable extent by known CYP3A4/5 substrates and/or inhibitors in human liver
      microsomes, and (3) in vitro-in vivo predictive calculations suggest that several
      compounds demonstrating CYP3A4-affinity might cause in vivo drug-drug
      interactions with zonisamide.

PMID- 9626926
TI  - Pharmacokinetics and cognitive effects of carbamazepine formulations with
      different dissolution rates.
AB  - OBJECTIVE: In this study our aim was to assess pharmacokinetic effects and
      adverse cognitive effects of switches between generic and branded formulations of
      carbamazepine (CBZ). METHOD: Twelve patients were included in a randomized open
      label, observer-blind, cross-over design with a double-baseline period, comparing
      three different formulations of carbamazepine in monotherapy--the innovatory
      branded form Tegretol and two generic forms, CBZ Pharmachemie and CBZ Pharbita.
      Cognitive assessment was carried out at baseline and 3 days after a cross-over.
      RESULTS: Area under the curve and a number of pharmacokinetic properties (serum
      concentration day curves, change in serum concentration (delta scores),
      peak/trough concentrations and peak time) did not differ among the three CBZ
      formulations. Therefore, the basic assumption for this study, i.e. to test
      pharmacokinetic-related differences in cognitive profile, was not met. In line
      with these findings, none of the cognitive variables showed statistically
      significant differences with respect to the cognitive profile during the day.
      CONCLUSION: Switches between the investigated generic CBZ formulations and the
      branded product did not result in any difference in cognitive profiles. These
      results are not necessarily valid, though, for other generic forms of CBZ, for
      other types of antiepileptic drugs or for CBZ treatment in higher doses or in
      polytherapy.

PMID- 9626927
TI  - Drug-induced systemic lupus erythematosus after 8 years of treatment with
      carbamazepine.
AB  - This is the report of a late-onset carbamazepine-induced systemic lupus
      erythematosus in a 34-year-old patient who had been treated with daily
      carbamazepine for 8 years because of complex partial seizures. When carbamazepine
      was discontinued, symptoms rapidly improved and antinuclear antibodies
      disappeared. So far, few cases have been reported of carbamazepine-induced lupus
      erythematosus within months after the start of treatment. This is the first case
      report about carbamazepine-induced systemic lupus erythematosus with serological
      confirmation after years of treatment without side effects.

PMID- 9626928
TI  - Suppression of macrophage activation by peritoneal fluid from patients with
      endometriosis.
AB  - To investigate the effects of peritoneal fluid from patients with endometriosis
      on mouse peritoneal macrophages (Mphi), peritoneal fluid from endometriosis
      patients (n = 15) were added to a monolayer of C3H/HeJ mouse peritoneal Mphi.
      Tumor necrosis factor-producing activity was measured by the L929 assay activated
      with FK-23 (a preparation of heat-killed Enterococcus faecalis). Tumor necrosis
      factor-producing activity of C3H/HeJ mouse peritoneal Mphi incubated with
      peritoneal fluid was suppressed in 14 endometriosis patients. Interestingly, in
      nine endometriosis patients, tumor necrosis factor-producing activity was much
      lower than seen with mouse peritoneal Mphi incubated with corticosterone.
      Peritoneal fluid contains suppressive properties for the activation of peritoneal
      Mphi, which might allow the implantation of free endometrial cells or the
      metaplastic phenomena stimulated by retrograde menstruation.

PMID- 9626929
TI  - Monoclonal antibodies with specificities for Streptococcus pneumoniae group 9
      capsular polysaccharides.
AB  - Streptococcus pneumoniae group 9 includes four capsular polysaccharide types: 9A,
      9L, 9N and 9V. We have generated four mouse monoclonal antibodies against group 9
      polysaccharide using heat-treated S. pneumoniae strains of different capsular
      polysaccharides types as immunogens. The specificities of the monoclonal
      antibodies were determined by ELISA using capsular polysaccharide directly coated
      to the wells as antigens and by dot blotting with heat-treated bacteria. Two
      groups of monoclonal antibodies were found. The first group included two
      monoclonal antibodies which were found to be capsular type specific. The second
      group was monoclonal antibodies that bound to epitopes shared by two or three
      pneumococcal group 9 types. The monoclonal antibody 204,A-4 (IgM) was found to be
      specific for S. pneumoniae type 9N. The binding of the type 9V specific
      monoclonal antibody 206,F-5 (IgG1) was found to be dependent upon O-acetyl
      groups. Monoclonal antibody 205,F-3 (IgM) reacted also with type 9V, but was
      found to cross-react with types 9A and 9L. The binding of this monoclonal
      antibody to polysaccharide 9V was not dependent upon O-acetyl moieties. The
      fourth monoclonal antibody (214,G-5, isotype IgM) did not show any correlation
      between reactivity with isolated polysaccharides and dot blotting with relevant
      bacteria. The monoclonal antibody reacted with polysaccharides 9A and 9L in
      ELISA, but not with the homologous bacteria.

PMID- 9626930
TI  - Effect of host Lewis and ABO blood group antigen expression on Helicobacter
      pylori colonisation density and the consequent inflammatory response.
AB  - The Lewis(b) blood group antigen has been implicated as a putative receptor for
      Helicobacter pylori in the gastric mucosa. Furthermore, an increased prevalence
      of duodenal ulcer was found in non-secretors and it has been suggested that
      secretor status may influence bacterial colonisation density. Other investigators
      have hypothesised that severity of antral gastritis may be related to
      colonisation density of the bacterium alone, and that a critical bacterial load
      is necessary for the development of duodenal ulcer. Our objectives were to
      investigate whether a relationship existed between host Lewis and ABO blood group
      phenotype and prevalence of H. pylori infection. In addition we investigated
      whether bacterial colonisation density and the ensuing inflammatory response was
      influenced by secretor status and ABO blood group phenotype. The Lewis and ABO
      blood group phenotype of 207 patients undergoing upper endoscopy was determined.
      Of these, 136 were secretors and 62 were nonsecretors. Forty-five percent of
      patients were infected with H. pylori. No significant association was found
      between H. pylori infection and expression of Lewis(a) or Lewis(b) blood group
      antigen. The mean histological density of H. pylori was 1.8 +/- 0.2 among non
      secretors and 1.51 +/- 0.13 among secretors (P = 0.209), with a mean grade of
      lymphocytic infiltration significantly greater in H. pylori-infected non
      secretors (2.23 +/- 0.123 vs 1.8 +/- 0.074; P = 0.003). In addition, blood group
      O non-secretors had a significantly higher grade of lymphocyte infiltration of
      their gastric mucosa compared to non-O non-secretors (2.53 +/- 0.133 vs 1.93 +/-
      0.181, P = 0.027). These results suggest that although no in vivo relationship
      exists between H. pylori and preferential adhesion to the putative Lewis(b)
      receptor, bacterial colonisation and the ensuing inflammatory response may be
      influenced at least in part by host expression of ABO and Lewisa blood group
      antigens.

PMID- 9626931
TI  - Antimycobacterial activity of chemically defined natural substances from the
      Caribbean flora in Guadeloupe.
AB  - Eight chemically defined, naturally occurring compounds were extracted from the
      tropical flora of the Caribbean island of Guadeloupe: pilocarpine, an alkaloid
      from Pilocarpus racemosus; heraclenol and isomeranzin, coumarins from Triphasia
      trifolia; lochnerin, an indole alkaloid from Rauwolfia biauriculata; ibogaine and
      voacangine, indole alkaloids from Tabernaemontana citrifolia; texalin, an oxazole
      from Amyris elemifera; and canellal, a sesquiterpene dialdehyde from Canella
      winterana. An essential oil fraction from Canella winterana was also tested. The
      antimycobacterial activity of these substances was tested against Mycobacterium
      tuberculosis, M. avium and M. kansasii using the Middlebrook 7H11 agar medium,
      the Bactec 460-TB radiometric methodology, and determination of bacterial viable
      counts. Three compounds, namely ibogaine, voacangine and texalin, showed
      antimycobacterial activity. Investigations on the structure-modification and
      structure-activity relationships of these compounds may help determine new
      targets for future drug development.

PMID- 9626932
TI  - Inhibition of Helicobacter pylori sialic acid-specific haemagglutination by human
      gastrointestinal mucins and milk glycoproteins.
AB  - Helicobacter pylori, a human gastric pathogen causing chronic gastritis and
      duodenal ulcer disease, has been found in large amounts in gastric mucous gel
      layer. Mucin preparations, separated from human gastric juices and isolated from
      different colon regions, were examined for their ability to inhibit
      haemagglutination of H. pylori with the emphasis on evaluating the role of sialic
      acid-dependent haemagglutinins of the bacteria in colonisation of the stomach.
      The mucins showed high inhibitory activity for H. pylori, which was significantly
      decreased after the removal of sialic acids from the mucins. The inhibitory
      potencies using high molecular mass mucin-like components from bovine milk were
      comparable with those obtained for gastric mucins, suggesting their possible role
      in the prevention of H. pylori infection.

PMID- 9626933
TI  - Extreme DNA sequence variation in isolates of Aspergillus fumigatus.
AB  - DNA sequence analysis of the alkaline protease gene was used to investigate two
      Aspergillus fumigatus strains isolated from ostriches (QLD1 and NSW3) and one
      environmental isolate (FRR 1266) that have shown genetic variation in previous
      analyses. The results showed that the QLD1 sequence was virtually identical to
      the published sequences for three human isolates but NSW3 differed in > 6% and
      FRR 1266 in > 10% of the nucleotides that were analysed. An RFLP assay was
      designed to determine the distribution of these (and other) genetic variants
      among environmental and clinical isolates of A. fumigatus.

PMID- 9626934
TI  - Suppression of major histocompatibility complex class I and class II gene
      expression in Listeria monocytogenes-infected murine macrophages.
AB  - Macrophage cells play a central role during infection with Listeria monocytogenes
      by both providing a major habitat for bacterial multiplication and presenting
      bacterial antigens to the immune system. In this study, we investigated the
      influence of L. monocytogenes infection on the expression of MHC class I and
      class II genes in two murine macrophage cell lines. Steady-state levels of I
      Abeta chain mRNA were decreased in both resting J774A.1 and P388D1 macrophages
      infected with L. monocytogenes whereas reduction of H-2K mRNA was only observed
      in P388D1 cells. In addition, L. monocytogenes suppressed induction of MHC class
      I and class II mRNAs in response to gamma-interferon as well as the maintenance
      of the induced state in activated P388D1 macrophages. Exposure to the non
      pathogenic species L. innocua or a deletion mutant of L. monocytogenes, which
      lacks the lecithinase operon, did not cause a reduction in H-2K and I-Abeta mRNA
      levels nor suppress expression of Ia antigens. Inhibition of MHC gene expression
      may represent an important part of the cross-talk between L. monocytogenes and
      the macrophage that probably influences the efficiency of a T cell-mediated
      immune response and thus the outcome of a listerial infection.

PMID- 9626935
TI  - Differentiation and distribution of three types of exfoliative toxin produced by
      Staphylococcus hyicus from pigs with exudative epidermitis.
AB  - Exfoliative toxins of approximately 30 kDa produced by Staphylococcus hyicus
      strains NCTC 10350, 1289D-88 and 842A-88 were purified and specific polyclonal
      antisera were raised against each of the toxins. It was shown by immunoblot
      analysis and ELISA that three exfoliative toxins from S. hyicus were
      antigenically distinct. The three toxins were designated ExhA, ExhB and ExhC.
      From 60 diseased pigs, each representing an outbreak of exudative epidermitis, a
      total of 584 isolates of S. hyicus were phage typed and tested for production of
      exfoliative toxin. ExhA-, ExhB- and ExhC-producing S. hyicus isolates were found
      in 12 (20%), 20 (33%) and 11 (18%), respectively, of the 60 pig herds
      investigated. Production of the different types of exfoliative toxin was
      predominantly associated with certain phage groups. However, toxin production was
      found in all of the six phage groups defined by the phage typing system. Some
      changes in the distribution of isolates between phage groups were observed when
      the results of this study were compared to previous investigations. In this study
      two new antigenically distinct exfoliative toxins were isolated and tools for in
      vitro detection of toxin producing S. hyicus isolates and for further studies on
      the exfoliative toxins from S. hyicus have been provided.

PMID- 9626936
TI  - Affinity purification of recombinant cholera toxin B subunit oligomer expressed
      in Bacillus brevis for potential human use as a mucosal adjuvant.
AB  - For use as a mucosal adjuvant for human vaccines, a simple method has been
      developed for the affinity purification of recombinant cholera toxin B subunit
      which had been expressed in a safe host, Bacillus brevis. Recombinant cholera
      toxin B subunit, adsorbed quantitatively to a D-galactose-agarose column, was
      eluted with an 0.1-0.4 M D-galactose gradient with a yield of > 90%. The cholera
      toxin B subunit preparation was similar to the native cholera toxin B subunit
      with respect to GM1 binding ability, remarkable stability of the pentamer, and
      the dissociation-reassociation property by shifting pHs. Cross-linking
      experiments with glutaraldehyde demonstrated that the pentameric form was
      predominant; tetrameric, trimeric, dimeric and monomeric forms were detected to a
      lesser extent, and additionally 10- and 15-mers were observed depending on the
      concentration of the cholera toxin B subunit.

PMID- 9626938
TI  - Inactivation of baroafferents leads to loss of barosensitivity without changes in
      nerve morphology.
AB  - Baroreceptors are stretch-sensitive mechanoreceptors, which are silenced by
      preventing distension of the receptor zone. Does chronic inactivation of these
      peripheral afferents alter their function or morphology? Compound action
      potentials and morphometry of carotid sinus nerves of 10 rabbits were
      investigated. The baroafferents were inactivated by embedding the pressure
      released carotid sinus into silicon gel. The success of this procedure was
      validated by the absence of spike activity of the sinus nerve during normal and
      elevated systemic blood pressure. The contralateral vessels of the same animals
      were sham-operated and also embedded into silicon, but without prevention of wall
      movements. After 5, 7, 14 or 28 days the nerves were functionally reinvestigated
      before and after release of the sinus wall. Afterwards, the morphology of the
      nerve cross-sections was analysed by morphometry of electron micrographs.
      Baroafferents did not regain spike activity during immobilisation of the sinus
      wall. After release of the carotid sinus wall only nerves inactivated for five
      days regained their pulse synchronous baroreceptor discharge. Following seven
      days of inactivation, baroreceptor discharge could be elicited by maximal
      pressure elevation in only one of three nerves. At any time later, the
      baroreceptor response to arterial pressure changes was lost completely. The
      activity of the control nerves was preserved after 28 days. No obvious
      differences in fibre size and myelin thickness were observed between inactivated
      and control nerves. Inactivation of baroafferents for more than one week leads to
      a loss of pressure-dependent spike activity. Since morphology did not differ
      between inactivated and control nerves, it is suggested that changes of
      baroreceptor endings are responsible for this loss of function.

PMID- 9626937
TI  - Mycobacterium tuberculosis reactive T cell clones from naturally converted PPD
      positive healthy subjects: recognition of the M. tuberculosis 16-kDa antigen.
AB  - Mycobacterium tuberculosis reactive T cell clones were established from naturally
      converted PPD-positive healthy subjects and screened for proliferative reactivity
      against defined M. tuberculosis protein antigens of 16, 19, 65 (HSP65), and 71
      (HSP70) kDa recombinantly expressed in Escherichia coli. Among the recombinant
      antigens tested, the M. tuberculosis 16-kDa protein antigen, as expressed from
      the lambda gt11 phage Y3155, was found to induce T cell proliferation.
      Crossreactivity studies showed that the epitope recognized was present in M.
      tuberculosis, M. africanum as well as the vaccine strain M. bovis BCG. The M.
      tuberculosis 16-kDa reactive T cell clone identified showed the CD4+, CD8-
      phenotype, secreted interferon-gamma upon antigen stimulation, and displayed
      major histocompatibility complex class II restricted cytotoxicity against M.
      tuberculosis pulsed macrophages. The results obtained suggest that the
      recombinant M. tuberculosis 16-kDa antigen can be recognized by human Th1 cells
      with potential relevance to protection.

PMID- 9626939
TI  - Sustained activation of muscle sympathetic outflow during static lung inflation
      depends on a high intrathoracic pressure.
AB  - Muscle sympathetic nerve activity is strongly activated during a static inflation
      of the lungs in awake human subjects. The purpose of the present study was to
      test the hypothesis that this sustained activation is due to the associated
      increase in intrathoracic pressure. In ten subjects microneurographic techniques
      were used to record muscle sympathetic activity from the peroneal nerve and
      arterial pressure was monitored continuously by finger-pulse
      photoplethysmography. Holding the breath at inspiratory capacity with the glottis
      closed and inspiratory muscles relaxed caused a sustained activation of muscle
      sympathetic nerve activity but not of skin sympathetic activity. Conversely, when
      subjects held the lungs maximally inflated by a constant inspiratory effort and
      an open glottis there was no sympathetic activation despite a similar initial
      fall in mean arterial pressure. Because intrathoracic pressure was below or close
      to atmospheric in the latter condition, it is concluded that a high intrathoracic
      pressure is required for the sympathetic response. Furthermore, the present
      results provide further support for the idea that unloading of cardiopulmonary
      baroreceptors is responsible for the sustained activation of muscle sympathetic
      nerve activity during static lung inflations in human subjects.

PMID- 9626940
TI  - Muscarinic receptor activation in guinea-pig chromaffin cells causes decreased
      membrane conductance and depolarization.
AB  - Membrane potentials were recorded with conventional intracellular microelectrodes
      from chromaffin cells in isolated, bisected adrenal glands from guinea-pigs. The
      local pressure ejection of muscarinic agonists, acetylcholine (in the presence of
      hexamethonium) or bethanecol, caused a transient depolarization that was
      relatively slow (1-2 s) in onset compared with the depolarization associated with
      the activation of nicotinic receptors. Muscarinic receptor-induced depolarization
      was associated with an increase in input resistance and the firing of action
      potentials. Repetitive stimulation of splanchnic nerve fibers within the gland,
      in the presence of hexamethonium, caused a maintained depolarization that was
      slow in both onset and decay and in many cells caused the repetitive firing of
      action potentials. It is suggested that, in this species, the exocytosis of
      catecholamines caused by the activation of muscarinic receptors, described by
      others, may be due to the initiation of tetrodotoxin-sensitive action potentials
      and consequent opening of voltage sensitive Ca2+ channels.

PMID- 9626941
TI  - Activation of A2a adenosine receptors in the nucleus tractus solitarius inhibits
      renal but not lumbar sympathetic nerve activity.
AB  - The activation of adenosine A2a receptors in the nucleus tractus solitarius (NTS)
      via microinjection of the selective agonist CGS 21680 elicits long-lasting, dose
      dependent decreases in mean arterial pressure (MAP) and heart rate (HR) and
      preferential dilation of the iliac vascular bed in comparison to the renal and
      mesenteric vascular beds. We investigated whether differential changes in
      regional sympathetic output occur with A2a receptor activation. In 24
      chloralose/urethane anesthetized male Sprague-Dawley rats MAP, HR, renal (RSNA)
      and lumbar sympathetic nerve activity (LSNA) were recorded simultaneously. Data
      were analyzed as both the maximum decrease and the integral of the decrease over
      the duration of the depressor response. Microinjection of CGS 21680 (2 and 20
      pmol in 50 nl volume) into the subpostremal NTS caused significant and dose
      dependent decreases in MAP, HR and RSNA, however, did not significantly decrease
      LSNA in comparison to the effect of vehicle. Maximum responses of RSNA vs. LSNA
      in delta% of control values were: -32 +/- 4 vs. -9 +/- 2, and -59 +/- 4 vs. -19
      +/- 5 for low (n = 9) and high (n = 8) doses of CGS 21680 respectively; integral
      responses of RSNA vs. LSNA in delta% x min were: -487 +/- 112 vs. -19 +/- 35 and 
      1258 +/- 164 vs. -175 +/- 126 for low and high doses of CGS 21680 respectively.
      Microinjections of vehicle (n = 7) did not alter integral hemodynamic or neural
      parameters. We conclude that activation of A2a adenosine receptors in the NTS
      evokes differential changes in visceral vs. somatic sympathetic nerve activity
      which cannot explain differential vascular responses in terms of simple
      sympathetic withdrawal. Lack of significant inhibition of LSNA combined with
      preferential vasodilation in hindquarter vascular bed suggests that active
      vasodilation may be triggered by activation of A2a adenosine receptors in the
      subpostremal NTS.

PMID- 9626942
TI  - Prejunctional facilitatory and inhibitory modulation of parasympathetic nerve
      transmission in the rabbit urinary bladder.
AB  - Release of [3H]choline and muscle contraction in response to electrical field
      stimulation were measured from rabbit detrusor muscle strips previously loaded
      with [3H]choline. The importance of different stimulation frequencies (1 and 10
      Hz) for activating either facilitatory or inhibitory prejunctional effects was
      examined in the presence of muscarinic and adrenergic (alpha2) receptor selective
      substances. At 1 Hz, neither [3H]choline overflow nor contraction was affected by
      the M1-selective receptor antagonist pirenzepine (10(-7) M), whereas overflow and
      contraction decreased at 10 Hz. The M1-selective receptor agonist McN-A-343 (10(
      6) M) caused no significant changes except for reducing contractions at 10 Hz.
      The M2-selective receptor antagonist methoctramine (10(-6) M), on the other hand,
      increased overflow as well as contraction at both frequencies, most conspicuously
      at 1 Hz. Atropine (10(-7) M) caused a significant increase with respect to
      overflow only at 1 Hz, while quite the opposite effect occurred with respect to
      contractions (reduced only at 10 Hz). Clonidine (10(-6) M) induced inhibition of
      [3H]choline overflow at 10 Hz only, but without significantly changing
      contractile responses. The results show that in the rabbit urinary bladder a
      muscarinic autoreceptor mediated inhibition (M2) of the transmitter release
      dominates during low frequency stimulation and that a facilitation (M1) may be
      present at stimulations with higher frequencies. However, this amplification may
      also be influenced by alpha2-adrenoceptor mediated inhibition.

PMID- 9626943
TI  - Baroreceptor-mediated reduction of jejunal mucosal perfusion, evaluated with
      endoluminal laser Doppler flowmetry in conscious humans.
AB  - Reduction of central blood volume elicits a peripheral vasoconstrictor reflex in
      various tissues including skin, skeletal muscle and the hepatomesenteric region.
      The aim of the present study was to investigate whether this reaction includes a
      decreased perfusion of the jejunal mucosa in man. Laser Doppler flowmetry (LDF)
      was used to monitor jejunal mucosal and skin perfusion simultaneously in eleven
      healthy volunteers. LDF recordings were performed during quiescent (phase 1)
      periods of the migrating motor complex. Seven subjects demonstrated cycling
      changes of jejunal mucosal perfusion (vasomotion). The average minimum jejunal
      flux value was 72 +/- 6 perfusion units. The average intraindividual coefficient
      of variation was 18 +/- 2%. Lower body negative pressure (LBNP) was used to
      elicit controlled reductions of central blood volume. LBNP of 10 mm Hg induced a
      12 +/- 4% (P < 0.05) decrease in jejunal perfusion and a 43 +/- 11 (P < 0.001)
      decrease in cutaneous perfusion. Corresponding responses to LBNP of 20 mm Hg were
      17 +/- 5% (P < 0.01) and 37 +/- 10% (P < 0.01) reductions in jejunal mucosal and
      skin perfusion, respectively. Cardiac index was significantly reduced by the LBNP
      procedure, whereas heart rate remained unchanged and blood pressure changes were
      minor and inconsistent. These findings indicate that the reflex vasoconstriction
      induced by mild central hypovolemia includes a significant reduction of jejunal
      mucosal perfusion in supine resting humans. This reflex may provide one mechanism
      for the intestinal ischemia often occurring in critically ill patients.

PMID- 9626944
TI  - The gain of the hepatorenal reflex in anesthetized dogs.
AB  - To determine the overall gain of the hepatorenal reflex, hypertonic NaCl
      solutions were infused into the portal vein or inferior vena cava of anesthetized
      dogs at a rate of 0.01 ml/kg/min for 30 min and the urinary Na excretion
      measured. Infusion of 2.25% NaCl into either the portal vein or inferior vena
      cava had no effect. Portal infusion of 4.5% or 9% NaCl produced an increase of 36
      +/- 16 or 40 +/- 17 microeq/kg/30 min, respectively, while inferior vena caval
      infusion had no effect. With 13.5% NaCl infusion, a significant increase in the
      natriuretic response was seen with portal venous infusion, with no significant
      difference between portal venous and inferior vena caval infusion. Thus, the
      difference in the natriuretic response between portal venous and inferior vena
      caval infusion was dependent on the degree of input; when an appropriate input
      was given, natriuresis was induced only by portal venous infusion, probably
      mediated by the hepatorenal reflex. The gain of the hepatorenal reflex was
      calculated from the output divided by the input. When 4.5% or 9% NaCl was infused
      into the portal vein, the 2-h gain of the hepatorenal reflex was 0.38 +/- 0.15 or
      0.34 +/- 0.14, respectively.

PMID- 9626945
TI  - Brainstem topology of the vagal motoneurons projecting to the esophagus and
      stomach in the house musk shrew, Suncus murinus.
AB  - The central origin of vagal efferents innervating the esophagus and stomach in
      the house musk shrew, Suncus murinus, was studied using the retrograde tracing
      technique. The animals were perfused with fixative 48-72 h after HRP injection
      and sections were processed by HRP histochemistry. HRP application into the
      gastroesophagus resulted in bilateral labelling of neurons in the dorsal motor
      nucleus of the vagus nerve (DMX) and ambiguous nucleus (AN). Labelled neurons in
      the DMX were observed from all regions except from the cervical esophagus, while
      ones in the AN were seen from the esophagus and cardia. The more labelled neurons
      were observed on the right DMX from subdiaphragmatic esophagus, cardia, lesser
      curvature and ventral corpus, while on the left DMX from the dorsal corpus
      labelled neurons in the longitudinal extent of the DMX were generally located at
      the dorsal and dorsomedial part, and those in the middle part were scattered.
      Labelled neurons in the AN were located restricted in the rostral part. Our
      results suggest that in the Suncus murinus the rostrocaudal site-specific
      localization within the DMX was not found, but it was prominent in the AN. In
      addition, while the majority of neurons which supply the esophagus and stomach
      were located in the DMX, only a small number was found in the AN.

PMID- 9626946
TI  - Immunohistochemical study of the c-kit expressing cells and connexin 43 in the
      guinea-pig digestive tract.
AB  - The distribution of the c-kit receptor expressing cells and gap junction protein,
      connexin (Cx) 43 in the guinea-pig stomach (antrum), small intestine (jejunum)
      and colon (ascending) was studied by immunohistochemistry. The anti-c-kit protein
      immunopositive cells were regularly observed in the myenteric region throughout
      all three organs. The immunopositive cells were also sparsely distributed in the
      circular muscle layer of both the stomach and the colon, but not in the small
      intestine. They were densely located in the regions of the deep muscular plexus
      (DMP) of the small intestine and submuscular plexus (SMP) of the colon. In
      contrast, strong immunoreactivity to anti-Cx 43 antibody was observed in almost
      the entire thickness of the circular muscle layer of the stomach and the small
      intestine, but not in the colon. Dense immunoreaction deposits were observed in
      the region of the DMP and SMP. However, only very weak immunoreactivity to anti
      Cx 43 antibody was detected in the myenteric region of all three organs. These
      results suggest that the c-kit receptor expressing cells or interstitial cells of
      Cajal (ICC) in the myenteric region of the three organs, and in the SMP of the
      colon, are poorly coupled with the bulk of circular muscle tissue by gap
      junctions, while ICC in the DMP and in the circular muscle layer of the stomach
      couple well with the surrounding muscle tissue.

PMID- 9626947
TI  - Single tube competitive PCR for quantitation of CMV DNA in the blood of HIV+ and
      solid organ transplant patients.
AB  - Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality in
      transplant and HIV-infected patients. However, CMV can also cause asymptomatic
      infection. An elevated blood viral load as assessed by various methods appears to
      be a predictor for symptomatic infections, and can be used to identify patients
      at the highest risk of developing CMV disease. We developed a single tube
      competitive quantitative PCR assay for CMV DNA, using as a competitor a plasmid
      carrying the target sequence for amplification with an internal deletion. The
      analysis of data from repeated extractions and amplifications of samples showed
      that the coefficient of variation of the assay was typically less than 20%.
      Clinical samples from 14 HIV-infected and 13 solid organ transplant patients were
      analyzed. Widely varying CMV DNA levels were found in leukocytes, with a positive
      correlation with the measure of infectivity in the leukocytes by quantitative
      culture on fibroblasts. The highest CMV DNA content in leukocytes was found in
      two patients with presumptive CMV disease. In HIV patients, the amount of DNA in
      leukocytes was much larger than in solid organ transplant recipients, when
      standardized for infectivity. Although based on a very limited number of
      patients, this observation probably points to a difference in the biology of CMV
      infection in these two categories of susceptible individuals. CMV DNA was also
      found in the plasma of some of the patients with a high CMV DNA leukocyte load.
      The present test should be useful for identifying patients at high risk of
      developing CMV disease, for monitoring therapeutic efficacy of antiviral regimens
      and to improve the understanding the pathogenesis of CMV infection.

PMID- 9626948
TI  - Biophysical characterization of GB virus C from human plasma.
AB  - Viral characterization studies were carried out on GB virus C (GBV-C) RNA
      positive plasma from normal human donors and from donors co-infected with GBV-C
      and hepatitis C virus (HCV). GBV-C RNA was detected by reverse-transcriptase
      polymerase chain reaction (RT-PCR) and probe hybridization in a single tube
      assay. Sequential filtration of GBV-C positive plasma indicated that GBV-C RNA is
      associated with a particle 50-100 nm in diameter. The peak of GBV-C RNA in
      sucrose gradients was observed at a buoyant density of 1.05-1.13 g/ml. GBV-C RNA
      titer was reduced following treatment with chloroform or with five detergents
      indicating that GBV-C has a lipid-containing envelope. Sucrose density gradients
      and self-forming cesium chloride gradients of detergent-treated GBV-C showed a
      shift in the RNA peak to heavier buoyant density only when RNase inhibitor
      (RNasin) and high detergent concentrations were present. The treated material was
      non-filterable and the RNA had a density of > 1.5 gm/ml.

PMID- 9626949
TI  - Endothelial cell monolayers as a model system to investigate dengue shock
      syndrome.
AB  - Monolayers of the human endothelial cell line ECV304 were compared with those
      from primary endothelial cells from human umbilical cord veins (HUVEC) for
      potential use as an assay system to investigate vasoactive mediator levels in
      dengue viral infections. Permeability increases were induced in ECV304 monolayers
      which were more easily reproduced than in primary cells. The cell line monolayers
      were considerably more stable which allowed multiple consecutive assays to be
      undertaken on the same monolayers. Permeability responsiveness was maximal at 2
      and 3 days postseeding and declined over a period of 7 days. The cell line formed
      monolayers which showed time- and concentration-dependent permeability increases
      in response to thrombin, tumour necrosis factor-alpha (TNF-alpha) or interleukin
      1alpha (IL-1alpha) in a manner similar to primary endothelial cells. Permeability
      increases induced by TNF-alpha were reversible and increased exposure time
      required a longer recovery period. The cell line, like primary endothelial cells,
      supported dengue viral replication. Direct infection of confluent monolayers on
      polycarbonate membranes was not cytolytic and did not increase the permeability
      of the monolayers over a 15-day period.

PMID- 9626950
TI  - Characterization and use of a recombinant retroviral system for the analysis of
      drug resistant HIV.
AB  - A recombinant retroviral system was used for the analysis of early HIV
      breakthrough infection in the presence of antiviral drugs. The use of replication
      defective HIV allowed a quantitative analysis of a single cycle of infection.
      This report characterizes this recombinant HIV system and demonstrates it's
      validity in comparison to standard assays. It is demonstrated that the protease
      inhibitor XM323 inhibits both early and late events in the HIV life-cycle, while
      dextran sulphate inhibits only early events. In addition, it is shown that this
      system can be used for detecting and quantitating drug resistant HIV. Thus, the
      use of this system may provide both novel information about the stage of the
      viral life-cycle inhibited and a preliminary assessment of the mechanism(s)
      responsible for breakthrough infection in the presence of antiretroviral drugs.

PMID- 9626951
TI  - The use of flow cytometry to detect antiviral resistance in human
      cytomegalovirus.
AB  - A method for detecting the antiviral susceptibility of human cytomegalovirus
      (HCMV) isolates to antiviral agents using flow cytometry was developed. This
      method has been used to detect the resistance phenotype of HCMV isolates to
      ganciclovir (GCV). The procedure involves infecting MRC-5 cells with 10(4) pfu
      HCMV for 120 h, then fixing and permeabilising the cells to allow intracellular
      labelling of the HCMV early and late antigens. The percentage reduction in the
      fluorescence positive population of HCMV-infected MRC-5 cells treated with GCV at
      concentrations of 20 or 50 microM compared with control cultures without GCV was
      determined. The IC50 defined as a < 50% reduction in the fluorescence positive
      population in cells infected in the presence of 20 microM GCV or an IC90 defined
      as a < 90% reduction in the fluorescence-positive population in cells infected in
      the presence of 50 microM GCV, correlated with resistance determined by a plaque
      reduction assay. The FACS assay is a rapid and reproducible method for detecting
      antiviral resistance of HCMV.

PMID- 9626952
TI  - Rapid identification of subgenera of human adenovirus by serological and PCR
      assays.
AB  - Bacterially expressed recombinant protein IX (pIX) of human adenovirus serotype 2
      (Ad2) and 3 (Ad3) was evaluated for use as a subgenus-specific antigen by enzyme
      linked immunosorbent assay (ELISA) and Western blotting. Patients sera positive
      by ELISA for the genus-specific adenovirus hexon antigen recognized the
      recombinant pIX of Ad2 and Ad3 in a subgenus-specific manner by both assays.
      Polyclonal rabbit serum raised against the recombinant Ad2pIX reacted strongly by
      indirect immunofluorescence assay, with Adl, 2 and 5 (subgenus C) but not with
      serotypes representing other subgenera. In a similar way, anti-Ad3pIX reacted
      with Ad3, 7, 11 and 14 (subgenus B), but not with serotypes representing other
      subgenera. A polymerase chain reaction showed that the complete pIX gene could be
      amplified in a subgenus specific fashion using primers specific for Ad3 (subgenus
      B), Ad2 (subgenus C), or Ad40/41 (subgenus F). The pIX gene from the available
      isolates of subgenus A, D and E was not amplified with these primers. The use of
      pIX-based serological assays is useful for subgenotyping as a primary screen of
      anti-Ad sera. It is much more rapid than the currently used neutralization assay
      or hemagglutination inhibition test. The application of anti-pIX sera by
      immunofluorescence and a pIX gene-based PCR are rapid methods which will improve
      subgenus identification of adenoviruses.

PMID- 9626953
TI  - Development and application of a new method for amplification and detection of
      human rhinovirus RNA.
AB  - A method based on nucleic acid sequence based amplification (NASBA) was developed
      for detection of rhinovirus RNA. Appropriate collection and storage conditions
      for maintenance of rhinovirus RNA integrity in clinical samples was determined.
      Two silica-based extraction methods were evaluated for preparation of RNA from
      virus isolates and clinical samples. Primers and probes were selected from the
      non-translated region at the 5' end and from VP4 of sequenced rhinoviruses.
      Amplified products were detected by 'in-solution' hybridization, with analysis by
      polyacrylamide gel electrophoresis (enzyme linked gel assay or ELGA), and by a
      microtitre-based plate hybridization assay. Using propagated picornavirus
      isolates in vitro the rhinovirus NASBA, with detection of amplified sequences by
      ELGA or plate hybridization, was confirmed as sensitive and specific for
      detection of rhinovirus RNA. The method was applied successfully to analysis of
      rhinovirus sequences in clinical samples from individuals with respiratory-tract
      symptoms. Rhinovirus NASBA will be useful for studies of the molecular
      epidemiology of respiratory infections and monitoring of response to anti
      rhinovirus therapy.

PMID- 9626954
TI  - In situ amplification of the Epstein-Barr virus genome in cell suspensions.
AB  - Epstein-Barr virus (EBV) is distributed widely throughout the world. Apart from a
      association with two geographically-restricted malignancies (Burkitt's lymphoma
      and nasopharyngeal carcinoma), EBV is thought to be implicated in the etiology of
      B-cell lymphoma in immunocompromised individuals. In these patients, monitoring
      the viral load in serum can provide useful information on the timing of the
      instigation of antiviral therapy, i.e. as soon as a rise is detected. PCR
      technology, owing to its high sensitivity, is used frequently in such situations.
      In order to gain further insight into the nature of the peripheral blood cells
      carrying the viral genome on a cell-by-cell basis, an in situ amplification
      technique was developed as a model using two cell lines growing in suspension,
      with the aim of distinguishing between EBV-positive and EBV-negative cells.
      Preliminary experiments were undertaken subsequently on clinical samples from
      patients with infectious mononucleosis and patients with lymphoma indicating that
      this technique might be useful clinically.

PMID- 9626955
TI  - A mixture of synthetic oligonucleotide probes labeled with biotin for the
      sensitive detection of potato spindle tuber viroid.
AB  - Five kinds of synthetic oligonucleotide probes labeled with biotin (BIO) were
      designed for the detection of potato spindle tuber viroid (PSTVd), and their
      sensitivities were compared with that of a digoxigenin (DIG)- or BIO-labeled cDNA
      probe. Although each oligonucleotide probe alone was less sensitive than the DIG
      cDNA probe, sensitivity was increased by using a mixture of two or all of the
      five oligonucleotide probes. The sensitivity of a PSmix1-5 probe, which was a
      mixture of five oligonucleotides, was the same as that of a DIG-labeled cDNA
      probe, which can detect 7.8 pg of purified PSTVd and PSTVd in nucleic acids,
      equivalent to extracts from 20 microg of infected potato leaf and 310 microg of
      infected potato tuber. Using the PSmix1-5 probe, PSTVd in all leaves and tubers
      of seven potato cultivars could be detected without any background. Moreover,
      with the PSmix1-5 probe, the hybridization time could be shortened to 2 h without
      any decrease in sensitivity, whereas the sensitivity of the cDNA probes clearly
      decreased when the hybridization time was shortened. Hybridization using a
      mixture of several oligonucleotide probes may be applicable to the gene diagnosis
      of other viroids and viruses.

PMID- 9626956
TI  - Sensitivity and reproducibility of RT-PCR to detect Borna disease virus (BDV) RNA
      in blood: implications for BDV epidemiology.
AB  - Borna disease virus (BDV) infection of domestic animals and humans appears to
      have a worldwide distribution. There is evidence suggesting an association of BDV
      with certain psychiatric disorders. However, more comprehensive epidemiological
      studies are required to establish rigorously a link between BDV and human mental
      disorders, and to evaluate the role of carrier animals as potential source of BDV
      for human infection. The use of RT-PCR to detect BDV RNA in peripheral blood
      mononuclear cells (PBMCs) of infected individuals is a powerful tool to address
      these questions. The comparison of discrepant results reported by different
      investigators using this approach is hampered by the lack of controls to assess
      the sensitivity and reproducibility of the assays. Procedures are now described
      that allow the establishment of standardized controls to evaluate the performance
      of the RT-PCR assays. This RT-PCR assay detected reproducibly 100 copies of BDV
      p40 RNA in 5 microg of RNA. The data illustrate that the number of PBMCs used for
      RNA preparation, rather than the amount of RNA, has a critical influence on the
      outcome of the RT-PCR assay. Evidence is provided that levels of BDV in blood do
      not necessarily reflect viral load in brain.

PMID- 9626957
TI  - AI in medical education--another grand challenge for medical informatics.
AB  - The potential benefits of artificial intelligence in medicine (AIM) were never
      realized as anticipated. This paper addresses ways in which such potential can be
      achieved. Recent discussions of this topic have proposed a stronger integration
      between AIM applications and health information systems, and emphasize computer
      guidelines to support the new health care paradigms of evidence-based medicine
      and cost-effectiveness. These proposals, however, promote the initial definition
      of AIM applications as being AI systems that can perform or aid in diagnoses. We
      challenge this traditional philosophy of AIM and propose a new approach aiming at
      empowering health care workers to become independent self-sufficient problem
      solvers and decision makers. Our philosophy is based on findings from a review of
      empirical research that examines the relationship between the health care
      personnel's level of knowledge and skills, their job satisfaction, and the
      quality of the health care they provide. This review supports addressing the
      quality of health care by empowering health care workers to reach their full
      potential. As an aid in this empowerment process we argue for reviving a long
      forgotten AIM research area, namely, AI based applications for medical education
      and training. There is a growing body of research in artificial intelligence in
      education that demonstrates that the use of artificial intelligence can enhance
      learning in numerous domains. By examining the strengths of these educational
      applications and the results from previous AIM research we derive a framework for
      empowering medical personnel and consequently raising the quality of health care
      through the use of advanced AI based technology.

PMID- 9626958
TI  - Fundamentals of clinical methodology: 2. Etiology.
AB  - The concept of etiology is analyzed and the possibilities and limitations of
      deterministic, probabilistic, and fuzzy etiology are explored. Different kinds of
      formal structures for the relation of causation are introduced which enable us to
      explicate the notion of cause on qualitative, comparative, and quantitative
      levels. The conceptual framework developed is an approach to a theory of
      causality that may be useful in etiologic research, in building nosological
      systems, and in differential diagnosis, therapeutic decision-making, and
      controlled clinical trials. The bearings of the theory are exemplified by
      examining the current Chlamydia pneumoniae hypothesis on the incidence of
      myocardial infarction.

PMID- 9626959
TI  - Neural networks for recognizing patterns in cardiotocograms.
AB  - The cardiotocogram (CTG) is commonly used for routine fetal monitoring in the
      delivery room. A major problem is that the interpretation of the CTG trace
      requires experienced specialists. In order to avoid long gaps between the
      detection of a suspicious pattern and the intervention, the CTG has to be checked
      in short intervals. An automated monitoring system at the obstetric site can
      reduce such delays. Therefore, an alarm system immediately reporting suspicious
      events has been built. The focus of our study was put on the question whether AI
      techniques such as neural networks are suited to the task of recognizing patterns
      in the CTG trace. In a comparative study, their performance was evaluated against
      that of conventional methods. The neural networks turned out to provide
      significantly better results than the tested conventional methods.

PMID- 9626960
TI  - Identification of 'genotoxic' and 'non-genotoxic' alerts for cancer in mice: the
      carcinogenic potency database.
AB  - A set of chemicals tested for carcinogenicity in mice that have been analyzed by
      Gold et al. [L.S. Gold, C.B. Sawyer, R. Magaw, G.M. Backman, M. deVeciana, R.
      Levinson, N.K. Hooper, W.R. Havender, L. Bernstein, R. Peto, M.C. Pike, B.N.
      Ames, Environ. Health Perspect. 58 (1984) 9-319; L.S. Gold, M. deVeciana, G.M.
      Backman, M. Lopipero, M. Smith, R. Blumenthal, R. Levinson, L. Bernstein, B.N.
      Ames, Environ. Health Perspect. 67 (1986) 161-200; L.S. Gold, T.H. Slone, G.M.
      Backman, R. Magaw, M. DaCosta, P. Lopipero, M. Blumenthal, B.N. Ames, Environ.
      Health Perspect. 74 (1987) 237-329; L.S. Gold, T.H. Slone, G.M. Backman, S.
      Eisenberg, M. DaCosta, M. Wong, N.B. Manley, L. Rohrbach, B.N. Ames, Environ.
      Health Perspect. 84 (1990) 215-286; L.S. Gold, N.B. Manley, T.H. Slone, T.H.
      Garfinkle, L. Rohrbach, B.N. Ames, Environ. Health Perspect. 100 (1993) 65-135]
      in the first five plots of the carcinogenic potency database (CPDB) was subjected
      to CASE/MULTICASE analyses. Briefly, CASE/MULTICASE is a computer-automated
      structure evaluation system that is capable of identifying structural features of
      chemicals associated with a specified biological activity (e.g., carcinogenicity
      or mutagenicity). These features are then incorporated into a structure-activity
      relationship (SAR) model for the analyzed database. The mouse CPDB used in this
      study consists of 627 chemicals, 289 of which are carcinogens, 11 marginal or
      weak carcinogens (i.e., chemicals requiring high doses to induce cancer) and 327
      non-carcinogens. In an internal prediction analysis where the CASE/MULTICASE SAR
      model was used to predict the carcinogenicity of chemicals used to create the
      model, a concordance between experimental and predicted results of 96% was
      obtained. This indicates that the model is able to satisfactorily explain the
      chemicals in the learning set. In a drop-one cross-validation study where
      chemicals were removed one at a time and the remaining n - 1 chemicals were used
      in an iterative method to create a model to predict the removed chemical,
      CASE/MULTICASE was able to achieve a concordance between experimental and
      predicted results of 70%. Using a modified validation process designed to
      investigate the predictivity of a more focused SAR model, the system achieved a
      78% concordance between experimental and predicted results. Among the major
      biophores identified by CASE/MULTICASE associated with cancer causation in mice
      several are derived from electrophilic or potentially electrophilic compounds
      (e.g., hydrazines, N-mustards, N-nitrosamines, aromatic amines, reactive
      halogens, and quinones). Other biophores however are derived from chemicals
      seemingly devoid of actual or potential DNA-reactivity and as such may represent
      structural feature of non-genotoxic carcinogens.

PMID- 9626961
TI  - Mutagenesis, tumorigenicity, and apoptosis: are the mitochondria involved?
AB  - Early studies have shown mitochondrially-mediated oxidative phosphorylation is
      diminished in cancer cells, with glycolysis being the main source of energy
      production. More recent provocative reports have indicated that the mitochondria
      may be involved in a host of different aspects of tumorigenesis, including
      mutagenesis, maintenance of the malignant phenotype, and control of apoptosis.
      These studies have broadened the possible roles mitochondria may play in
      malignancy. Further studies to define the importance of mitochondria should
      revolve around the functional assessment of these changes in vitro and in vivo,
      and will be interesting for determining their significance in human cancer.

PMID- 9626962
TI  - Chromosomal aberrations induced by 12C6+ heavy ion irradiation in spermatogonia
      and spermatocytes of mice.
AB  - The testes of Kun-Ming strain mice were radiated with different doses of 12C6+
      ion or 60Co gamma-ray. Chromosomal aberrations induced in spermatogonia and
      spermatocytes were analyzed by the air-drying method. The relative biological
      effectiveness (RBE) of 12C6+ ion was calculated with respect to 60Co gamma-ray
      for the induction of chromosomal aberrations. The 12C6+ ion and 60Co gamma-ray
      dose-response relationships for chromosomal aberrations were plotted by linear
      quadratic models. The results showed that there was an increase in frequency of
      chromosomal aberrations in all the treated groups compared to controls. The RBE
      values were 1.67 for aberrations of spermatogonia and 1.66 for aberrations of
      spermatocytes for a dose of 2.0 Gy. Moreover, a different distribution of the
      various types of aberrations has been found for 12C6+ ion and 60Co gamma-ray
      irradiations. The dose-response relationships for 12C6+ ion and 60Co gamma-ray
      exhibited negative curvature in both spermatogonia and spermatocytes groups: the
      frequencies of aberrations increased sharply at low doses and exhibited less
      sharp increases for higher doses, which may be related to an interaction between
      the chromosomal damage and a block in cell cycle. Our results may provide useful
      information for the assessment of genetic risks of humans exposed to heavy ions.

PMID- 9626963
TI  - Roles of the mutagenesis proteins SamA'B and MucA'B in chemically induced
      frameshift mutagenesis in Salmonella typhimurium hisD3052.
AB  - The mutagenesis induced by ultraviolet light and many chemicals in Escherichia
      coli is largely dependent upon the proteins encoded by the umuDC operon and their
      analogs. In Salmonella typhimurium, there are two sets of umuDC-like operons: the
      umuDC(ST) operon in the chromosome and the samAB operon located on the 60-MDa
      cryptic plasmid. The former operon, but not the latter, confers UV mutability on
      S. typhimurium. Nevertheless, the samAB operon, when carried on high-copy-number
      plasmids, can efficiently promote UV mutagenesis. In order to characterize the
      function of samAB in greater detail, we have compared the abilities of MucA'B and
      a putative activated form of SamAB, i.e. SamA'B, to promote chemically induced
      frameshift mutagenesis in S. typhimurium hisD3052. MucAB is an activated form of
      the products of mucAB, which is the most potent umuDC analog characterized so
      far. We have used four plasmids, each carrying samA', samB, mucA' or mucB with a
      lac promoter instead of their own promoters. The results indicated that under the
      conditions of elevated expression, SamA'B can promote chemically induced
      frameshift mutagenesis by furylfuramide, aflatoxin B1, 1-nitropyrene, and 1,8
      dinitropyrene, with efficiencies comparable to, or even better than, MucA'B.
      Increase of the levels of expression enhanced the ability of SamA'B to promote
      the mutagenesis, while it decreased that of MucA'B. Surprisingly, the elevated
      expression of MucB alone significantly enhanced the frameshift mutagenesis
      induced by 1-nitropyrene and 1,8-dinitropyrene, whereas the elevated expression
      of SamB, MucA' and SamA' did not enhance it. These results suggest that the
      abilities of SamA'B and MucA'B to promote mutagenesis strongly depend on their
      levels of expression. The possible roles of these mutagenesis proteins in
      chemically induced frameshift mutagenesis are discussed.

PMID- 9626964
TI  - Association of the NAT1*10 genotype with increased chromosome aberrations and
      higher lung cancer risk in cigarette smokers.
AB  - The NAT1 gene exhibits polymorphisms in the non-coding polyadenylation region
      with a number of alleles. Of these alleles, NAT1*10 is responsible for increased
      NAT1 enzyme levels and is reported to be associated with increased risk for
      colorectal and bladder cancers. In view of the possible role of the NAT1 gene
      product in the metabolism of a number of cigarette smoke carcinogens, we tested
      the possibility that genetic variation in the NAT1 gene might also be associated
      with increased risk for lung cancer. Allelic variances of the NAT1 gene were
      analyzed in 45 lung cancer patients and 47 controls who were matched with respect
      to age, race and gender using restriction fragment length polymorphism (RFLP)
      analysis and allele-specific (AS)-PCR. Our results indicate that individuals who
      inherited the NAT1*10 allele had a 3.7-fold increased relative risk for lung
      cancer (95% CL = 1.2-16.0, p < 0.02). There was a 6.8-fold increase in relative
      risk for lung cancer associated with the inheritance of the NAT1*10 allele in
      younger individuals (< 60 years of age) compared to 2.2-fold increase in older
      individuals (> 60 years old) (OR = 6.8; 95% CL = 1.1-40.7, p < 0.01 and OR = 2.2;
      95% CL = 0.5-11.1, p = 0.2, respectively). We have also applied the sensitive
      fluorescence in situ hybridization (FISH) tandem probe assay to elucidate the
      frequency of chromosome breakage among a subgroup of the studied individuals
      harboring the NAT1*10 allele (17 lung cancer patients, 17 smoking controls and 7
      non-smoking controls). Our results indicate a significant increase (p < 0.001) in
      the frequency of chromosome breaks in lung cancer patients (mean +/- SE per 100
      cells = 1.45 +/- 0.11) and in smoking controls (1.30 +/- 0.13) compared to non
      smoking controls (0.47 +/- 0.07). Regression analysis indicated a highly
      significant positive correlation between the duration of smoking in years and the
      frequency of chromosome breaks in lung cancer patients (r = 0.62, p = 0.008), but
      not in smoking controls (r = 0.02; p = 0.91). These findings suggest that NAT1
      polymorphism may be an important genetic determinant of lung cancer risk. In
      addition, these data provide a mechanistic link between the inheritance of the
      NAT1*10 allele and smoking-induced lung cancer. Given that the NAT1 enzyme can
      mediate activation and detoxication pathways for numerous carcinogens and given
      that this polymorphism is prevalent in the general population (20-50% frequency),
      it may play a significant role in influencing the outcome of a variety of
      environmental cancers.

PMID- 9626965
TI  - Mutagenic action of 5-nitroimidazoles: in vivo induction of GC-->CG transversion
      in two Bacteroides fragilis reporter genes.
AB  - The in vivo mutagenic potential of two 5-nitroimidazoles, metronidazole and
      dimetridazole, was evaluated in Bacteroides fragilis, a strictly anaerobic
      bacterium. Two antibiotic resistance genes, tetA(Q)3 and nimA, were used as DNA
      targets. The forward and back mutations were identified by nucleotide sequence
      analysis. Both drugs induced GC-->CG transversion exclusively. The results
      suggest that the reactive molecules generated during the intracellular reduction
      of the 5-nitroimidazoles are responsible for both base pair substitutions and DNA
      strand breaks, although the mechanisms and targets may be different.

PMID- 9626966
TI  - A high yield of translocations parallels the high yield of sister chromatid
      exchanges in the CHO mutant EM9.
AB  - The fluorescence plus Giemsa (FPG) and fluorescence in situ hybridization (FISH)
      techniques have been used to determine, respectively, the frequencies of sister
      chromatid exchanges (SCEs) and stable chromosome aberrations (translocations)
      induced by different concentrations of BrdU in the Chinese hamster ovary cell
      mutant EM9 and its parental line AA8. The results indicate that BrdU induced a
      high frequency of SCEs and translocations in EM9 as compared with AA8, and that
      the translocation/dicentric ratio was also higher in the mutant cell line than in
      the parental cell line in both untreated and BrdU-treated cultures. These
      observations may indicate a possible relationship between the molecular
      mechanisms involved in the formation of SCEs and translocations.

PMID- 9626967
TI  - The effect of benzenediols and benzenetriols on the nitrosation of propranolol
      depends on the position of hydroxyl groups on the benzene ring.
AB  - Nitrosation of propranolol under the standard conditions recommended by the World
      Health Organization (10 mM propranolol hydrochloride, 40 mM sodium nitrite, pH
      3.5) was carried out in the absence and in the presence of phenol, benzenediols
      and benzenetriols added to the nitrosation mixture in concentrations ranging from
      2 to 40 mM. The yield of N-nitrosopropranolol (NOP) was reduced, with potency
      decreasing in the following order, by 1,2-benzenediol > 1,2,3-benzenetriol > 1,4
      benzediol; their inhibiting effect was dose-dependent. 1,2,4-Benzenetriol
      displayed a significant inhibitory activity only at 20-40 mM concentrations. The
      maximum reduction of NOP formation (7% of the yield obtained under control
      conditions) was produced at 120 min by 40 mM 1,2-benzenediol. In contrast, the
      yield of NOP was increased by 1,3-benzenediol and 1,3,5-benzenetriol, but this
      effect was inversely related to the concentration. The effect of the various
      phenols on the time course of propranolol nitrosation was dependent on both the
      test phenol and its concentration. 1,2-Benzenediol and 1,3-benzenediol displayed
      on the nitrosation of proline effects qualitatively of the same type, but
      quantitatively different, as compared with those observed on the nitrosation of
      propranolol. Taken as a whole, the results of this study indicate that depending
      on the positions of hydroxyl groups on the benzene ring benzenediols and
      benzenetriols may inhibit or hasten nitrosation reactions.

PMID- 9626968
TI  - Methyl methanesulfonate-induced hprt mutation spectra in the Chinese hamster cell
      line CHO9 and its xrcc1-deficient derivative EM-C11.
AB  - The Chinese hamster cell mutant EM-C11, which is hypersensitive to the cell
      killing effects of alkylating agents compared to its parental line CHO9, has been
      used to study the impact of base excision repair on the mutagenic effects of DNA
      methylation damage. This cell line has a defect in the xrcc1 gene. XRCC1 can
      interact with DNA polymerase-beta, thereby suppressing strand displacement, and
      DNA ligase III, both of which have been implicated in base excision repair. XRCC1
      may, therefore, allow efficient ligation of single-strand breaks generated during
      base excision repair. Both EM-C11 and CHO9 cells were treated with methyl
      methanesulfonate (MMS), a DNA-methylating agent reacting predominantly with
      nitrogen atoms generating adducts which are substrates for the base excision
      repair pathway. EM-C11 cells are much more sensitive to the cytotoxic effects of
      MMS than CHO9: for EM-C11, the dose of MMS inducing 10% survival is 6-fold lower
      than that for CHO9. In contrast, mutation induction at the hprt locus following
      MMS is similar in EM-C11 and CHO9. Molecular analysis of hprt gene mutations
      showed that although the largest class of hprt mutations, both in EM-C11 and CHO9
      cells, consisted of GC > AT transitions, most likely caused by O6-methylguanine,
      the size of this class was smaller in EM-C11. The fraction of deletion mutants in
      EM-C11, however, was twice as large as that found in CHO9 cells. These results
      suggest that reduced ligation efficiency of single-strand breaks generated during
      base excision repair, as result of a defect in XRCC1, may lead to the formation
      of deletions.

PMID- 9626969
TI  - Frequency of HPRT gene mutations induced by N-methyl-N'-nitro-N-nitrosoguanidine
      corresponds to replication error phenotypes of cell lines.
AB  - We have examined whether cells with replication error-positive (RER+) and 
      negative phenotype (RER ) respond differently to the mutagen MNNG, employing
      three RER+ and two RER- human cell lines. Cells were treated with several
      concentrations of MNNG, and HPRT mutants were selected phenotypically by their
      growth in the presence of 6-thioguanine. While the variation of the mutation
      frequency within each group was about an order of magnitude, it was found that
      MNNG induced a level of mutations in the HPRT gene some 100- to 1000-fold higher
      in RER+ cells than in cells with RER-phenotype. MNNG, at a concentration of 30
      microM, produced a mutation frequency 450-fold higher in HCT116 (RER+) cells than
      in SW480 (RER-) cells. Our findings suggest that the RER+ phenotype predisposes
      cells to MNNG-induced hypermutability.

PMID- 9626970
TI  - The distribution of the tail moments in single cell gel electrophoresis (comet
      assay) obeys a chi-square (chi2) not a gaussian distribution.
AB  - The parameter tail moment in single cell gel electrophoresis (comet assay) is
      calculated as the product of the two values: the percentage of DNA in the comet
      tail and the tail length in microm. Experiments were performed with cultured
      mammalian cells: B-Lymphoblasts, epithelial cells of a kidney tissue and a plate
      epithelial cell line of a human carcinoma. They were irradiated in suspension
      with UV A at lambda = 343 nm, generated by an excimer laser-pumped dye laser. DNA
      migration was assessed and analysed. It is demonstrated that the distribution of
      the tail moments can be fitted by a chi2 (chi-square) distribution, whereas the
      factors of the product tail moment tend to be normally distributed. From this
      result, consequences for the statistical evaluation of the results can arise,
      especially for the computation of the confidence limits and for the valuation of
      the parameter tail moment from other comet assay experiments.

PMID- 9626971
TI  - MOCA and some proposed substitutes (Cyanacure, Conacure, Polacure 740M and
      Ethacure 300) as two-stage skin carcinogens in HRA/Skh hairless mice.
AB  - 4,4'-Methylenebis(2-chlororaniline) (MOCA) is a suspect human carcinogen that has
      wide use as an industrial compound. Occupationally, exposure may occur through
      inhalation and ingestion, but skin absorption is the main route by which this
      compound gains entry into the body. Because of the justified concern about the
      continued use of MOCA, a number of substitutes have been proposed, including 1,2
      bis(2-aminophenylthio)ethane (Cyanacure), Conacure, trimethylene glycol di-p
      aminobenzoate (Polacure 740M) and 3,5-dimethylthio-2,4-toluenediamine/3,5
      dimethylthio-2,6-tol uenediamine (Ethacure 300). There is very little information
      available about these substances, but they share the property of belonging to the
      same class (aromatic amines) as MOCA. Furthermore, at least two (Ethacure 300 and
      Cyanacure) are mutagenic in Salmonella. This study was undertaken to investigate
      if MOCA and substitutes, Polacure 740M, Ethacure 300, Cyanacure and Conacure have
      the potential to cause papillomas in a two stage initiation/promotion protocol in
      HRA/Skh hairless mice. When a maximum dose of 100 mg of substance was applied to
      the dorsal skin of these mice, Ethacure 300 and Cyanacure were markedly toxic.
      All of the compounds had little or no effect on skin tumor initiating activity
      following 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion. One experiment
      with MOCA suggested that, at lower and less toxic dose, this substance may have
      promotional activity. Therefore, caution should still be exercised when using
      these compounds and it cannot be excluded that they may be active in other
      strains of mice or other laboratory animal species.

PMID- 9626972
TI  - Comparison between in vivo mutagenicity and carcinogenicity in multiple organs by
      benzo[a]pyrene in the lacZ transgenic mouse (Muta Mouse).
AB  - To evaluate whether the in vivo mutagenicity test system using the lacZ
      transgenic mice (Muta Mouse) may be applied to carcinogenesis studies, both the
      in vivo mutagenicity and carcinogenicity of benzo[a]pyrene (BP) was tested in
      mice under the same administration conditions. The eleven organs of the mice on
      the 14th day after the final oral administration of BP at a dose of 125 mg kg(-1)
      day(-1) or corn oil for 5 consecutive days were tested for in vivo mutation by
      the positive-selection method. The data show that the colon had the highest lacZ
      mutant frequency (37-fold increase over the spontaneous frequency), followed by
      the ileum > forestomach > bone marrow, spleen > glandular stomach > liver, lung >
      kidney and heart. No significant mutations were found in the brain. These results
      may suggest that, in general, the organs with rapidly proliferative tissues have
      a marked increase in vivo mutant frequencies under the conditions of this
      experimental design. The forestomach and lymphatic organs including the spleen
      (malignant lymphoma) were the main target organs for BP carcinogenesis by 5 daily
      oral doses of 75 and 125 mg kg(-1) day(-1). These results suggest that the
      mutation results from the transgenic assay with BP reflect the carcinogenicity of
      BP in the mouse. They also indicate, however, that the magnitude of the in vivo
      lacZ mutant frequencies induced by BP in different organs did not fully correlate
      with the target organs for carcinogenicity.

PMID- 9626973
TI  - Construction of a umuC'-luxAB plasmid for the detection of mutagenic DNA repair
      via luminescence.
AB  - This paper describes a novel system for the detection of mutagenic DNA repair in
      Escherichia coli. The DNA damage inducible umuC gene of Escherichia coli has been
      fused to the luxAB genes from Vibrio harvleyi that encode the enzyme luciferase.
      Mutagenicity has been assessed semi-quantitatively by the induction of
      bioluminescence. This system is simple, rapid and equivalent in sensitivity to
      other currently available test procedures. Its use in the detection of known SOS
      mutagens MMS, MNNG and UV is described.

PMID- 9626974
TI  - Hepatocarcinogenesis (Z#2)/mutagenesis during initiation stage.
AB  - Previously, we developed a model for high incidence, endogenously generated
      hepatocellular carcinoma (HCC), the human alpha-1-antitrypsin (alpha1AT) Z gene
      transgenic mouse (Z#2). We now examine the potential utility of a model for
      endogenous carcinogenesis utilizing the Z#2 mouse also transgenic for the lacI
      gene, a convenient target for in vivo mutagenesis studies. We crossed the Z#2
      line and mice transgenic for lambda/lacI shuttle vector (Big Blue), for
      determination of lacI mutant frequency during initiation of endogenous
      carcinogenesis. Five month old double transgenic mice (Z#2+/lacI+) successfully
      displayed: (1) the expected post-inflammatory stage of Z#2 carcinogenesis; and
      (2) hepatic lacI mutants measured at frequencies (10(-5)-10(-4)) useful to
      mutagenesis studies. In this study, hepatic lacI mutation frequencies in Z#2
      transgenic mice appeared to be only slightly increased (< 2x) when compared to
      age matched negative controls. In the future, it may be important to reconcile
      possibly limited lacI mutagenesis at the time of initiation and demonstrated high
      incidence of hepatocarcinogenesis.

PMID- 9626975
TI  - An examination of DNA strand breakage in the comet assay and antioxidant capacity
      in diabetic patients.
AB  - There are two forms of diabetes, insulin-dependent Diabetes mellitus (IDDM) and
      non-insulin dependent Diabetes mellitus (NIDDM). There is evidence to suggest
      that reactive oxygen is involved in the pathogenicity and complications arising
      from IDDM, but there is little to suggest a role of oxidative stress in the
      pathogenesis of NIDDM. In order to investigate this hypothesis further,
      peripheral blood samples were taken from control individuals and IDDM and NIDDM
      patients and examined for antioxidant capacity and in the Comet assay for DNA
      strand breakage. The individuals answered a questionnaire to provide information
      relating to lifestyle factors in case such factors might have a confounding
      effect. There were 20 controls, 22 IDDM patients and 23 NIDDM patients. No
      differences could be detected in control and diabetic patient groups in terms of
      creatinine levels and antioxidant capacity. DNA damage in the Comet assay was at
      a lower level than in the control in the IDDM patients and a slightly lower level
      in the NIDDM patients, which might indicate that these cells are handling more
      oxidative damage on a regular basis. As expected, there were differences in
      glycosylated haemoglobin (HbA(1C)) levels. The confounding factors (smoking,
      drinking and vitamin intakes, etc.) appeared to have no effect.

PMID- 9626976
TI  - Effect of vindesine sulfate on the radiation-induced alterations in mouse
      spermatogenesis: a flow cytometric evaluation.
AB  - The effect of 0.05 mg/kg body weight of vindesine sulfate was studied on the
      radiation-induced changes in mouse spermatogenesis at 1, 2, 7, 14, 21, 28, 35 and
      70 days post-irradiation. Vindesine administration before exposure to 0, 0.5, 1,
      2 and 3 Gy gamma-irradiation resulted in an increase in the radiation-induced
      perturbations of mouse spermatogenesis at various post-exposure time periods
      studied. A significant reduction in testicular weight was observed in both DDW +
      irradiated and VDS + irradiated groups at various post-irradiation time periods,
      depending on the exposure dose. Vindesine pretreatment resulted in an enhanced
      killing of spermatogonial cells at day 2 post-exposure at all the exposure doses,
      except 3 Gy when compared to DDW + irradiated controls. Consequently, the
      tetraploid (4C) population declined significantly by day 14 post-irradiation
      followed by a severe depletion in round spermatids (1C) by day 21 post
      irradiation. The dose-response relationship for 4C and 1C populations was linear
      quadratic at days 14 and 21, respectively. A significant elevation was observed
      in HC population from days 1 to 21 depending on the exposure dose. The germ cell
      ratios, viz. 4C:2C, 4C:S-phase, 1C:2C and 1C:4C, showed a significant decline in
      the VDS + irradiated group when compared to the DDW + irradiated group at various
      time periods, depending on the exposure dose.

PMID- 9626977
TI  - Catabolite repressors are potent antimutagens in Escherichia coli plate
      incorporation assays: experiments with glucose, glucose-6-phosphate and methyl
      alpha-D-glucopyranoside.
AB  - Having previously found that the yields of spontaneous valine-resistant (Val(r))
      Escherichia coli mutants which appeared on plates containing 40 microg/ml of
      valine were always much lower when glucose was present in the glycerol-containing
      defined medium normally used to select them, we now sought to determine whether
      or not the global regulatory mechanism known as catabolite repression (formerly
      also called glucose repression) might be involved. We therefore tested glucose
      (the archetypal catabolite repressor), glycerol (a non catabolite-repressing
      substrate), glucose-6-phosphate (G6P, an exceptionally powerful catabolite
      repressor) and methyl-alpha-D-glucopyranoside (alphaMG, a strongly catabolite
      repressing but non-utilisable glucose analogue), as potential inhibitors of
      spontaneous mutagenesis in plate incorporation assays, using three distinct
      mutation detection systems. We found that the numbers of spontaneous Val(r) and
      Lac+ mutations appearing on the selective plates tended to be highest when the
      medium contained only a non-repressing primary carbon source (glycerol in the
      Val(s) --> Val(r) system, lactose in the Lac- --> Lac+ system) and lowest when it
      had been supplemented with a strongly catabolite-repressing compound such as
      alphaMG, G6P or glucose. These results would seem to establish that catabolite
      repression is an important factor in determining the outcome of the spontaneous
      mutation generation process in E. coli and hence that the numbers of spontaneous
      mutations which can be expected to arise in any given set of mutation assay
      conditions may often be dependent upon the levels of catabolite repression which
      prevail during the course of the assay. The implications of these results for
      conventional plate-incorporation mutation assays are discussed.

PMID- 9626978
TI  - Inhibitory effects of ellagic acid on the direct-acting mutagenicity of aflatoxin
      B1 in the Salmonella microsuspension assay.
AB  - Ellagic acid (EA) is a phenolic compound that exhibits both antimutagenic and
      anticarcinogenic activity in a wide range of assays in vitro and in vivo. It
      occurs naturally in some foods such as strawberries, raspberries, and grapes. In
      the previous work, we used the Salmonella microsuspension assay to examine the
      antimutagenicity of EA against the potent mutagen aflatoxin B1 (AFB1) using
      tester strains TA98 and TA100. Briefly, the microsuspension assay was
      approximately 10 times more sensitive than the standard Salmonella/microsome
      (Ames) test in detecting AFB1 mutagenicity, and EA significantly inhibited
      mutagenicity of all AFB1 doses in both tester strains with the addition of S9.
      The greatest inhibitory effect of EA on AFB1 mutagenicity occurred when EA and
      AFB1 were incubated together (with metabolic enzymes). Lower inhibition was
      apparent when the cells were first incubated with EA followed by a second
      incubation with AFB1, or when the cells were first incubated with AFB1 followed
      by a second incubation with EA alone, all with metabolic enzymes. The result of
      these sequential incubation studies indicates that one mechanism of inhibition
      could involve the formation of an AFB1-EA chemical complex. In the present study,
      we further examine the effect of EA on AFB1 mutagenicity, but without the
      addition of exogenous metabolic enzymes. We report the mutagenicity of AFB1 in
      the microsuspension assay using TA98 and TA100 without the addition of S9.
      Neither the concentrations of AFB1 (0.6, 1.2, and 2.4 microg/tube) nor the
      concentrations of EA (0.3, 1.5, 3, 10, and 20 microg/tube) were toxic to the
      bacteria. The results indicate that AFB1 is a direct-acting mutagen, and that EA
      inhibits AFB1 direct-acting mutagenicity.

PMID- 9626979
TI  - Transgenic rodent mutation/cancer bioassays: cell cycle control, cell
      proliferation and apoptosis as modifiers of outcome.

PMID- 9626980
TI  - Cellular resistance and hypermutability in mismatch repair-deficient human cancer
      cell lines following treatment with methyl methanesulfonate.
AB  - Resistance to the cytotoxic effects of S(N)1 alkylating agents such as N-methyl
      N'-nitro-N-nitrosoguanidine (MNNG) and N-methyl-N-nitrosourea (MNU) is well
      established in mismatch repair-defective cells, however, little is known about
      the cellular response to S(N)2 alkylating agents in these cells. Here we describe
      the cytotoxic response and the mutagenic response at the hypoxanthine-guanine
      phosphoribosyl transferase (HPRT) locus to the S(N)2 alkylating agent methyl
      methanesultfonate (MMS) in human cancer cell lines defective in mismatch repair
      (MMR). Our findings suggest that cytotoxicity to MMS is mediated through MMR, as
      indicated by an increased resistance to MMS in MMR-deficient cells. Cells in
      which specific MMR-gene defects were complemented by chromosome transfer were
      generally more sensitive to the cytotoxic effects of MMS. Additionally, the
      induced mutant frequency at HPRT following exposure to MMS is significantly
      increased in MMR-deficient lines. These findings suggest that resistance to S(N)2
      alkylation damage is mediated by MMR genes, and that resistance to such damage in
      MMR-defective cells correlates with an increase in genomic mutations. The results
      are consistent with the hypothesis that abasic sites may be substrates for repair
      involving MMR-gene products in human cells.

PMID- 9626981
TI  - New insights into the regulation of megakaryocyte differentiation and platelet
      production derived from cloning of thrombopoietin and its receptor: surprises and
      unresolved questions as thrombopoietin proceeds through clinical trials.

PMID- 9626982
TI  - A recurrent theme with a new spin: ACE polymorphism and cardiovascular disease.

PMID- 9626983
TI  - Platelet kinetics in autosomal dominant macrothrombocytopenia.
AB  - A family with autosomal dominant macrothrombocytopenia is described. Despite
      severe thrombocytopenia, only a moderate hemorrhagic tendency was observed.
      Kinetic studies revealed a normal platelet survival, normal megakaryocytic
      numbers, and normal bone marrow responsiveness. The rate of platelet production
      was set low, despite moderately impaired hemostasis and thrombocytopenia; it
      apparently was set to maintain another platelet parameter at an optimal level.
      Measurements of total circulating platelet mass and platelet surface suggested
      that the platelet production was set to maintain the platelet surface rather than
      the platelet mass at a normal value.

PMID- 9626984
TI  - Regulation of megakaryocytopoiesis and platelet production: lessons from animal
      models.

PMID- 9626985
TI  - DD genotype of the angiotensin I-converting enzyme gene is a risk factor for
      early onset of essential hypertension in Japanese patients.
AB  - Although angiotensin-converting enzyme (ACE) plays an important role in blood
      pressure regulation, no relationship between the insertion/deletion (I/D)
      polymorphism of the ACE gene and essential hypertension has been observed.
      However, as the pathogenesis and genetic background of essential hypertension are
      heterogeneous, we investigated whether the ACE gene is a marker of subgroups of
      patients with essential hypertension. A group of 178 patients with essential
      hypertension (90 men/88 women; 53 +/- 13 years of age, mean age +/- SD ) and 101
      normotensive control subjects (54 men/47 women; 51 +/- 14 years of age, mean age
      +/- SD ) were included in the study. The allele frequencies of the two groups
      were similar. There were no differences in age, blood pressure, retinopathy
      grade, presence of proteinuria, or resting plasma renin activity (PRA) among the
      hypertensive patients with the II, ID, and DD genotypes. However, the age of
      onset of hypertension of patients with the DD genotype was lower (p < 20.05) and
      their left ventricular mass index was higher (p < 2 0.05) than those in patients
      with the non-DD genotype. These data suggest that the I/D polymorphism of the ACE
      gene is associated with an early onset of hypertension and left ventricular
      hypertrophy in Japanese patients with essential hypertension.

PMID- 9626986
TI  - Quantitative assessment of platelets, platelet microparticles, and platelet
      aggregates with flow cytometry.
AB  - With fluorescent beads it has become possible to determine absolute numbers of
      cells in a given sample instead of relative percentages on a standard flow
      cytometer. This study assesses the ability to count platelets, microparticles,
      and aggregates with a flow cytometer. Whole blood was stimulated with 0.1 U
      thrombin per milliliter. Platelet and microparticle counts decreased, while the
      number of aggregates increased. Unactivated whole blood was diluted with buffer
      and showed a corresponding decrease in the concentration of platelets,
      microparticles, and aggregates. The platelet count on the flow cytometer was
      always in good correlation with counts on an automated blood analyzer. Only the
      cytometer, and not the automated analyzer, was able to detect and count
      microparticles and aggregates. In highly diluted samples of unactivated whole
      blood there was a spurious relative increase in CD62p-positive platelets because
      of a surplus of anti-CD62p antibodies and a relative increase in microparticles.
      Flow cytometry is a valuable method for counting platelets, aggregates, and
      microparticles in unstimulated and activated blood samples. If the platelet count
      changes and drops to less than 50% of the count for which the amount of antibody
      and the cytometer settings have initially been adjusted, care has to be taken to
      avoid misinterpretation.

PMID- 9626987
TI  - The role of oxygen free radicals in cisplatin-induced acute renal failure in
      rats.
AB  - We examined the role of oxygen free radicals in cisplatin-induced acute renal
      failure (ARF). The intravenous injection of cisplatin (5 mg/kg body weight)
      induced an increase in serum creatinine and tubular damage in the outer stripe of
      the outer medulla in rats. The renal content of malondialdehyde (MDA) transiently
      increased. Treatment with the free radical scavengers dimethylthiourea (DMTU) or
      lecithinized superoxide dismutase (L-SOD) attenuated the increase in serum
      creatinine. The beneficial effect of DMTU, a hydroxyl radical scavenger, was
      associated with less accumulation of MDA, less tubular damage, and enhanced
      expression of proliferating cell nuclear antigen (PCNA) in the damaged tubular
      cells, but not with improvement of reduced renal blood flow (RBF). On the other
      hand, the beneficial effect of L-SOD, a superoxide anion scavenger, was
      associated with preservation of RBF and increased urinary guanosine 3',5'-cyclic
      monophosphate excretion but not with modification of tubular damage or PCNA
      expression. These results suggest that (1) cisplatin-induced nephrotoxicity was
      associated with lipid peroxidation, (2) the hydroxyl radical scavenger prevented
      ARF through both attenuation of tubular damage and enhanced regenerative response
      of the damaged tubular cells, and (3) the superoxide anion scavenger did the same
      through preservation of RBF. It follows that oxygen free radicals may play an
      important role in cisplatin-induced ARF by reducing RBF and inducing tubular
      damage.

PMID- 9626988
TI  - Effect of serotonin and thromboxane A2 on endothelial cell proliferation: effect
      of specific receptor antagonists.
AB  - Platelet aggregation at sites of vascular injury releases both peptide growth
      factors and vasoactive compounds. Although significant attention has been focused
      on peptide growth factors, very little is known about the mitogenic effect of
      vasoactive compounds. We evaluated the effect of serotonin (5-HT) and thromboxane
      A2 (TXA2) mimetic U46619 alone and in combination on aortic endothelial cells.
      Stimulation of endothelial cells by 5-HT resulted in an increase in tritiated
      thymidine uptake and an increase in cell number, whereas U46619 did not have any
      significant effect. However, when endothelial cells were exposed to both
      compounds, U46619 potentiated the mitogenic effect of 5-HT on endothelial cells.
      When endothelial cells were preincubated with LY281067 (a 5-HT2 receptor
      antagonist) or ridogrel (a combined TXA2 synthase inhibitor and receptor
      antagonist), LY281067 blocked the mitogenic effect of 5-HT and ridogrel blocked
      the potentiating effect of U46619 on 5-HT2-induced tritiated thymidine
      incorporation. When endothelial cells were preincubated with both antagonists,
      the effects of both 5-HT and U46619 were blocked. Recent studies have indicated
      that regenerating endothelial cells at sites of vascular injury may release
      growth factors for vascular smooth muscle cells, leading to smooth muscle cell
      proliferation and development of neointima. This study suggests that the combined
      use of 5-HT and TXA2 receptor antagonists may inhibit the growth of endothelial
      cells at sites of vascular injury and attenuate the formation of neointima.

PMID- 9626989
TI  - Rat gastric mucosal cells express ICAM-1 and proinflammatory cytokines during
      indomethacin-induced mucosal injury.
AB  - Adhesion molecules and cytokines are known to be involved in the formation of
      acute gastric mucosal injury. However, it is not clear whether the gastric
      mucosal cells express these molecules and modulate the inflammation. To clarify
      whether gastric mucosal cells express intercellular adhesion molecule-1 (ICAM-1)
      and proinflammatory cytokines (tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1-alpha (IL-1-alpha), and cytokine-induced neutrophil chemoattractant
      2-beta (CINC-2-beta)) in the formation of gastric mucosal injury, we have used
      rat indomethacin-induced gastric mucosal lesions as an in vivo model. The gene
      expression of all cytokines and ICAM-1 increases at the early stages of
      indomethacin-induced gastritis (TNF-alpha and IL-1-alpha gene expression began to
      increase earlier than that of ICAM-1 and CINC-2-beta) and can mainly be detected
      in the gastric epithelial layer. To further identify the source of those
      molecules, the epithelial cells were separated into seven fractions according to
      their sizes by a counterflow elution. ICAM-1 and CINC-2-beta gene expressions are
      particularly enhanced in the middle-sized cell fractions that are rich in gastric
      mucous-producing cells. The effect of TNF-alpha or IL-1-alpha on the gene
      expression of ICAM-1 and cytokines was examined by using RGM-1 cells as a model
      for gastric mucosal cells. RGM-1 cells show an augmented ICAM-1 and
      proinflammatory cytokine expression in response to TNF-alpha or IL-1-alpha
      stimulation. Moreover, immunohistochemical staining also reveals an increase in
      ICAM-1 and CINC protein production in RGM-1 cells in response to TNF-alpha
      stimulation. We conclude that gastric mucosal cells express various cytokines and
      an adhesion molecule during the formation of acute gastric mucosal injury and
      that they may modulate the inflammation.

PMID- 9626990
TI  - Reactivity patterns of antiphospholipid antibodies and endothelial cells: effect
      of antiendothelial antibodies on cell migration.
AB  - Antiphospholipid syndrome (APS) is characterized by the presence of a
      heterogeneous class of antibodies directed against phospholipids and associated
      with high occurrence of thrombotic complications. Antiendothelial cell antibodies
      (AECAs) have been identified in various autoimmune disorders including APS, but
      their reactivity patterns remain unclear. We used eluted endothelial membrane
      bound antibodies (EC eluates) to investigate possible cross-reactivity of AECAs
      and their pathogenic effects on endothelial cell integrity. The heterogeneous and
      nonspecific nature of AECAs was confirmed by our finding that they cross-react
      with fibroblasts and platelets and bind to cardiolipin. In addition, platelet
      bound antibodies from sera of patients with APS reacted with endothelial cells. A
      dose-dependent binding of human monoclonal anticardiolipin antibody was
      demonstrated, but this antibody did not compete with AECAs in EC eluates,
      indicating that only small portion of AECAs are directed against cardiolipin.
      Although sera from APS patients prolonged coagulation tests, EC eluates did not
      affect coagulation, suggesting that AECAs may belong to antiphospholipid
      antibodies subsets that does not interfere with coagulation. Vascular damage is a
      common feature of autoimmune disorders associated with AECAs. Possible effects of
      AECAs on vascular perturbance were investigated by cytotoxicity, attachment, and
      migration assays. Although AECAs were not shown to be cytotoxic or to affect cell
      attachment, sera from APS patients caused reduced cellular migration (by 30%),
      and EC eluates caused even more significant inhibition (by 50%). These findings
      suggest possible interference of AECAs in vascular repair mechanisms and provide
      an explanation for the thrombotic complications frequently seen in APS patients.

PMID- 9626991
TI  - The fortieth anniversary of thrombopoietin (or is it the fiftieth?).

PMID- 9626992
TI  - Synergistic neurotoxic effects of combined treatments with cytokines in murine
      primary mixed neuron/glia cultures.
AB  - Activation of brain glial cells with the bacterial endotoxin lipopolysaccharide
      (LPS), the HIV-1 coat protein gp120, or beta-amyloid-derived peptides, stimulates
      the expression of several cytokines, including tumor necrosis factor-alpha
      (TNFalpha), interleukin-1 (IL-1) and IL-6. and nitric oxide (NO) which have been
      proposed as causes of neurodegeneration in the brain. In the present study, the
      neurotoxic effects of several cytokines, alone or in various combinations, and
      the correlations of the release of lactate dehydrogenase, the loss of neurons,
      and the secretion of NO in brain neuronal cell injury were investigated in murine
      primary mixed neuronal/glial cell cultures. A specific combination of cytokines,
      i.e., IL-1 (1 ng/ml)+ TNFalpha (10 ng/ml)/interferon-gamma (IFNgamma) (200 u/ml),
      induced a dramatic neuronal cell injury in the neuron/glia cultures, and its
      cytotoxic profile was very similar to that seen with the LPS/IFNgamma-induced
      neuron injury. This indicates that among the many toxic immune mediators secreted
      in response to LPS, IL-1 and TNFalpha can mimic LPS as the triggering signals and
      primary mediators for glia-mediated neuron injury in the presence of IFNgamma.
      This study provides new insights about the cytotoxic mechanism(s) for cytokine
      mediated neuron injury.

PMID- 9626993
TI  - Expression of NGF receptors in normal and pathological human thymus.
AB  - The expression of NGF receptors was investigated in normal human thymus and in
      thymic hyperplasias, thymomas and thymic carcinomas. By RT-PCR, we detected TrkAI
      transcripts encoding for the high-affinity NGF receptor. Western blot analysis
      showed the presence of both TrkA and p75NGFR proteins. In normal thymuses,
      epithelial subcapsular and medullar cells were TrkA immunoreactive.
      Interdigitated medullar cells were stained for both TrkA and p75NGFR. While
      epithelial cells of normal thymuses or benign thymomas exhibited a TrkA positive
      p75NGFR negative phenotype, a switch to a TrkA negative-p75NGFR positive
      phenotype was observed in malignant epithelial cell tumours and was associated
      with cell proliferation-associated MIB1 expression. Our results argue for a local
      role of NGF and its receptors on thymic stromal cells both in normal and
      neoplastic conditions.

PMID- 9626994
TI  - Detection of skewed T-cell receptor V-beta gene usage in the peripheral blood of
      patients with multiple sclerosis.
AB  - The ex vivo analysis of the T-cell receptor V-beta (TCRBV) gene usage by
      circulating T lymphocytes in Multiple Sclerosis (MS) patients may contribute to
      understanding disease pathogenesis. In the present study, TCRBV gene usage was
      analyzed in freshly collected unstimulated peripheral blood mononuclear cells
      (PBMC) isolated from 40 MS patients and 20 healthy controls. Nine patients
      presented abnormal repertoires, with expansion of one or more TCRBV segments.
      Among these patients, six presented expansion of TCRBV9 chain expression, three
      also having an expansion of TCRBV1, TCRBV11 and TCRBV22 segments. The most
      frequently observed TCRBV chain expansion, TCRBV9, was further analyzed and
      identified as polyclonal. Evaluation of clinical variables showed that median
      disease duration was shorter in patients with TCRBV gene expression
      abnormalities. Longitudinal evaluation of five patients with a skewed repertoire
      showed regression of expanded TCRBV chains expression to normal values. These
      data indicate that certain MS patients have abnormal TCRBV gene expression. Such
      abnormalities are caused by polyclonal expansions of T lymphocyte subpopulations
      that use the same TCRBV gene families, are unstable and preferentially observed
      early in the course of the disease.

PMID- 9626995
TI  - Chemokines and chemotaxis of leukocytes in infectious meningitis.
AB  - Chemokines constitute a constantly growing family of small inflammatory
      cytokines. They have been implied in many different diseases of the CNS including
      trauma, stroke and inflammation, e.g., multiple sclerosis. In this review we
      focus on the role of chemokines in infectious meningitis of bacterial or viral
      origin. In experimental bacterial meningitis induced by Listeria monocytogeneses
      both CXC and CC chemokines namely MIP-1alpha, MIP-1beta and MIP-2 are produced
      intrathecally by meningeal macrophages and leukocytes which infiltrate into the
      CNS. In patients with bacterial meningitis, IL-8, GROalpha, MCP-1, MIP-1alpha and
      MIP-1beta are detectable in the CSF. These chemokines contribute to CSF mediated
      chemotaxis on neutrophils and PBMC in vitro. In viral meningitis IL-8, IP-10 and
      MCP-1 are identified in the CSF to be responsible for chemotactic activity on
      neutrophils, PBMC and activated T cells. Taken collectively these data indicate
      that the recruitment of leukocytes in infectious meningitis involves the
      intrathecal production of chemokines.

PMID- 9626996
TI  - Gender variations in early Theiler's virus induced demyelinating disease:
      differential susceptibility and effects of IL-4, IL-10 and combined IL-4 with IL
      10.
AB  - Theiler's murine encephalomyelitis virus (TMEV) induced demyelinating disease, is
      an animal model of multiple sclerosis (MS). The viral-induced encephalitis is
      followed by an inflammatory and demyelinating disease. We quantitated the
      response of female and male mice during the transition from encephalitis to early
      demyelination. CNS neuropathology and antiviral antibody production were
      evaluated. Parallel studies were done with anti-inflammatory cytokines IL-4, IL
      10 or a combination of IL-4 with IL-10. Results show female mice demonstrate an
      augmented susceptibility to the virus and a greater response to the cytokine
      therapies. Significant variation was noted during early demyelinating disease.
      The combination therapy of IL-4 with IL-10 produced striking decreases in
      antiviral antibody levels and virus-induced neuropathologic disease. Male mice
      are less susceptible to viral-induced disease and are less responsive to the
      cytokine treatments. Gender bias in TMEV-induced demyelinating disease appears to
      parallel the differences noted with other experimental immune diseases.

PMID- 9626997
TI  - The expression of co-stimulatory and accessory molecules on cultured human muscle
      cells is not dependent on stimulus by pro-inflammatory cytokines: relevance for
      the pathogenesis of inflammatory myopathy.
AB  - Specific activation of naive T cells requires TCR engagement plus interaction of
      CD28 on T cells with co-stimulatory B7-1/B7-2 on APCs. Since muscle cells may be
      directly involved in activating muscle-infiltrating T lymphocytes in polymyositis
      and inclusion body myositis, we analyzed B7 expression on myoblasts before and
      after treatment with pro-inflammatory cytokines. We found no expression of B7
      1/B7-2, either constitutively or after stimulus with cytokines. Furthermore,
      myoblasts failed to stimulate alloreactive peripheral blood lymphocytes in mixed
      lymphocyte reactions. Lack of B7 expression was confirmed by immunostaining of
      polymyositis patients' muscle: only T and the few B lymphocytes present in
      inflammation areas expressed B7-1.

PMID- 9626998
TI  - Anti-CD3 activation of human CD4+ T cells increases expression of the
      intracellular beta-endorphin endopeptidase (IDE/gamma-EpGE).
AB  - In this study, increased expression of an endopeptidase hydrolyzing beta
      endorphin (beta-Ep) to gamma-endorphin (gamma-Ep, beta-Ep1-17) was observed upon
      immobilized anti-CD3 stimulated activation of human peripheral blood CD4+ T cells
      (hCD4+ T cells). Although freshly isolated hCD4+ T cells are devoid of
      significant beta-Ep endopeptidase activity ( < 0.1 nmol h(-1) 10(6) cells (-1)),
      activation of these cells with immobilized anti-CD3 results in a time dependent
      appearance of beta-Ep endopeptidase activity which reaches a maximal value of
      17.4+/-0.48 nmol h(-1) 10(6) cells(-1) after 48 h of culture. Significant up
      regulation of both mRNA encoding IDE/gamma-EpGE and immunoreactive protein are
      observed in anti-CD3 stimulated hCD4+ T cells, indicating transcription and
      translation of IDE/gamma-EpGE may be elevated. No significant hydrolysis of
      exogenous beta-Ep is observed with intact hCD4+ T cells whether quiescent or
      activated or from preparations of hCD4+ T cell membranes. Therefore, this
      activity appears to be intracellular. Immunoreactive IDE/gamma-EpGE is detected
      inside activated hCD4+ T cells. Analysis of metabolites generated upon hydrolysis
      of beta-Ep with lysed activated hCD4+ T cell preparations identified the presence
      of: beta-Ep1-18, beta-Ep2-18, beta-Ep1-17, beta-Ep2-17, beta-Ep18-31, beta-Ep19
      31, beta-Ep1-13, beta-Ep2-13, beta-Ep18-26, and beta-Ep20-31 as major metabolites
      and the majority of these are consistent with beta-Ep hydrolytic activity
      attributable to IDE/gamma-EpGE.

PMID- 9626999
TI  - 5D4 keratan sulfate epitope identifies a subset of ramified microglia in normal
      central nervous system parenchyma.
AB  - Microglia expressing keratan sulfate (KS) was studied in normal central nervous
      system (CNS) and in rat neonatal brain cultures. The majority of KS+ cells are
      ramified microglia located in the brain parenchyma; positive cells were only
      exceptionally found in extraparenchymal structures. KS+ cells are ubiquitous, but
      their density is heterogeneous throughout the CNS. Serial sections incubated with
      anti-KS MAb and MAb against the complement receptor type 3 (CR3) revealed a
      higher number of CR3+ cells and double immunofluorescence showed the presence of
      two microglial populations: the first expressing both KS and CR3, the second
      expressing only CR3. Two sets of microglial cells were found also in neonatal rat
      microglial cultures where only a low percentage of microglial cells expressing
      CR3 was also KS+. KS was not induced by microglia activation.

PMID- 9627000
TI  - Single amino acid analogs of a myasthenogenic peptide modulate specific T cell
      responses and prevent the induction of experimental autoimmune myasthenia gravis.
AB  - Peptide p259-271 of the human acetylcholine receptor alpha-subunit,
      preferentially stimulates T cells of patients with myasthenia gravis (MG) and is
      an immunodominant epitope for T cells of BALB/c mice. A p259-271 specific T cell
      line of BALB/c origin was established and was shown to induce experimental MG in
      naive mice. Seven analogs of p259-271 were synthesized, and two of them were
      found to inhibit the p259-271 specific proliferative responses of the line and of
      p259-271 primed lymph node cells. Moreover, the most efficient inhibitor, analog
      262Lys, prevented the MG related manifestations in mice inoculated with the line,
      and might be of potential value for the treatment of MG.

PMID- 9627001
TI  - Interleukin-1 receptor antagonist suppresses experimental autoimmune
      encephalomyelitis (EAE) in rats by influencing the activation and proliferation
      of encephalitogenic cells.
AB  - Considering the role of pleiotropic interleukin-1 (IL-1) in inflammation and
      autoimmunity, studies were designed to examine whether specific blockade of IL-1
      may influence these processes in the CNS. Although the role of CD4+ T cells in
      eliciting clinical signs of experimental autoimmune encephalomyelitis (EAE) has
      been unequivocally demonstrated, the exact mechanism by which encephalitogenic
      cells initiate disease process and bring about clinical signs still remains to be
      defined. We have evaluated the effect of human recombinant interleukin-1 receptor
      antagonist (IL-1Ra) in vivo on the course of actively induced EAE in highly
      susceptible Dark Agouti (DA) rats. The rats which were treated during the
      induction phase of disease (days 0-6) with IL-1Ra (350 microg/rat/day) developed
      milder signs of EAE, when compared to saline-treated control animals immunized
      with encephalitogen, which developed severe single episode disease. The transfer
      of lymph node cells (LNC) isolated from MBP-primed DA rats and stimulated in
      vitro with MBP and ConA to naive syngeneic animals resulted in the development of
      EAE in all recipients. However, rats injected with LNC that have been stimulated
      in vitro in the presence of IL-1Ra (10 microg/ml) developed significantly milder
      disease. Diminished encephalitogenic capacity of LNC correlated with lower
      proliferative response to antigen and mitogen and decreased expression of IL-2
      receptors. These data provide further evidence that IL-1 is an important factor
      for activation of EAE inducing T lymphocytes.

PMID- 9627002
TI  - Synthetic peptides fail to induce nasal tolerance to experimental autoimmune
      myasthenia gravis.
AB  - Nasal administration of Torpedo acetylcholine receptor (AChR) to Lewis rats prior
      to induction of experimental autoimmune myasthenia gravis (EAMG) is highly
      efficient in prevention of clinical weakness, and suppression of AChR-specific T
      and B cell responses. To identify possible antigenic determinants within the
      receptor which can modulate EAMG and anti-AChR response, we evaluated the effects
      of nasal administration of alpha 61-76, alpha 100-116, alpha 146-162, delta 354
      367, and alpha 261-277 of Torpedo AChR at different doses on the tolerance
      induction against EAMG irrespective if given at lower, the same or higher doses
      than whole Torpedo AChR protein, that was confirmed to be highly efficient as
      tolerogen to EAMG. None of these peptides, neither administrated alone nor in
      combination, induced tolerance to EAMG. Peptide administration did not affect the
      levels or affinities of anti-AChR antibodies when compared with non-tolerized
      control EAMG rats, while administration of whole AChR protein affected both
      variables. The results may indicate that the T and B cell heterogeneity of AChR
      epitopes makes it difficult to induce tolerance using synthetic peptide.

PMID- 9627003
TI  - Structural differences between HLA-DQ molecules associated with myasthenia gravis
      characterized by molecular modeling.
AB  - Myasthenia gravis (MG) is characterized by muscle weakness due to autoimmunity
      against the nicotinic acetylcholine receptor (nAChR). MG is associated with
      polymorphisms in HLA-DQ genes and the aim of the present study was to
      characterize structural differences in the peptide binding groove of HLA-DQ
      molecules positively and negatively associated with MG. Three dimensional models
      of the positively associated DQ2 (DQB1*02) and negatively associated DQ6
      (DQB1*0603) molecules were constructed by homology modeling techniques. The
      differences in peptide binding properties were primarily localized to peptide
      anchor pockets P7 and P9, which might be of importance for the binding of disease
      associated peptides from the nAChR.

PMID- 9627004
TI  - Th1- and Th2-like cytokines in CD4+ and CD8+ T cells in autism.
AB  - Th1-like (IL-2, IFN-gamma) and Th2-like (IL-4, IL-6, and IL-10) cytokines were
      examined in CD4+ and CD8+ T cells in children with autism. Intracellular
      cytokines were measured using specific antibodies to various cytokines and anti
      CD4 or anti-CD8 monoclonal antibodies by FACScan. Proportions of IFN-gamma+CD4+ T
      cells and IL-2+CD4+ T cells (Th1), and IFN-gamma+CD8+ and IL-2+CD8+ T cells (TC1)
      were significantly lower in autistic children as compared to healthy controls. In
      contrast, IL-4+CD4+ T cells (Th2) and IL-4+CD8+ T cells (TC2) were significantly
      increased in autism. The proportions of IL-6+ CD4+, IL-6+CD8+ and IL-10+CD4+, IL
      10+CD8+ T cells were comparable in autism and control group. These data suggest
      that an imbalance of Th1- and Th2-like cytokines in autism may play a role in the
      pathogenesis of autism.

PMID- 9627005
TI  - Review: angiogenesis: implications for rheumatoid arthritis.

PMID- 9627006
TI  - Review: Magnetic resonance imaging of normal and osteoarthritic cartilage.

PMID- 9627007
TI  - Effect of intraarticular hyaluronan injection in experimental canine
      osteoarthritis.
AB  - OBJECTIVE: To determine if intraarticular injections of hyaluronan (HA) protect
      against the early stages of joint damage in a canine model of osteoarthritis
      (OA). METHODS: OA was induced in adult mongrel dogs by transection of the
      anterior cruciate ligament of the left knee. One group of dogs (n=7) was treated
      with 5 weekly injections of HA (MW 1,500,000) into the operated knee beginning 1
      day after ligament transection. The control group (n=6) was injected with saline
      on the same schedule. Twelve weeks after surgery, all dogs were killed, the
      severity of pathologic changes of OA was graded, and composition of the cartilage
      and extent of aggregation of proteoglycans (PGs) synthesized in vitro by
      cartilage slices were determined. RESULTS: All dogs showed gross morphologic
      changes typical of OA in the unstable knee. The severity of joint pathology in HA
      treated dogs was comparable with that in the saline-injected controls. In OA
      cartilage from the saline-treated group, the mean uronic acid concentration was
      30-60% greater than that in the contralateral knee. In sharp contrast, the uronic
      acid concentration in OA cartilage from the HA-treated dogs was 10-30% lower than
      that in cartilage from the contralateral knee (P=0.02 and P=0.03, respectively,
      for samples from the medial and lateral femoral condyle). The extent of
      aggregation of PG synthesized in vitro by cartilage from HA-injected animals was
      similar to that synthesized by cartilage from the saline-injected dogs.
      CONCLUSION: In this canine model of OA, the series of intraarticular injections
      of HA did not alter development of osteophytosis or fibrillation. However, the PG
      concentration of cartilage in the OA knee was significantly reduced by this
      treatment, suggesting that HA therapy might adversely affect the biomechanical
      properties of the cartilage.

PMID- 9627008
TI  - Severe disturbance of the distribution and expression of type VI collagen chains
      in osteoarthritic articular cartilage.
AB  - OBJECTIVE: The aim of this study was to evaluate the messenger RNA (mRNA)
      expression and distribution of the major pericellular type VI collagen in normal
      and osteoarthritic (OA) cartilage. METHODS: Conventional and confocal laser
      scanning immunohistochemistry, as well as in situ hybridization experiments, were
      performed for all 3 collagen type VI chains in sections of normal and OA
      articular cartilage. RESULTS: Normal adult articular chondrocytes were surrounded
      by a type VI collagen-positive pericellular matrix and showed significant levels
      of mRNA expression for all 3 type VI collagen chains. In OA cartilage, the
      expression and overall distribution of type VI collagen was largely increased in
      the lower middle and upper deep zones. In contrast, the upper zones showed a
      significant loss of pericellular type VI collagen staining. CONCLUSION: Our
      results suggest that there is a significant basic turnover of type VI collagen in
      normal articular cartilage. In OA cartilage, the chondrocytes of the lower middle
      and upper deep zones account for a net increase in type VI collagen synthesis.
      The loss of type VI collagen staining in the upper zones is most likely the
      result of increased protein degradation rather than reduced synthetic activity.

PMID- 9627009
TI  - Regulation of cartilage oligomeric matrix protein synthesis in human synovial
      cells and articular chondrocytes.
AB  - OBJECTIVE: Cartilage oligomeric matrix protein (COMP) is a component of the
      extracellular matrix of articular cartilage. Its increased presence in synovial
      fluid and serum has been associated with accelerated joint damage in patients
      with rheumatoid arthritis (RA) and osteoarthritis. To fully understand the
      reasons for fluctuations of COMP levels, we studied the biosynthesis of this
      molecule in cells derived from joint tissues. METHODS: Synovial cells were
      derived from synovial tissues of patients with RA, and human articular
      chondrocytes were prepared from normal articular cartilage. Analysis by Northern
      blotting was used to evaluate steady-state levels of COMP messenger RNA (mRNA),
      while secretion of the protein into culture media was analyzed by Western
      blotting. Expression of COMP in synovial tissues was studied by reverse
      transcriptase-polymerase chain reaction analysis and by in situ hybridization.
      RESULTS: COMP was synthesized and secreted by synovial cells as well as by
      articular chondrocytes in culture. The basal rate of synthesis was very low;
      however, COMP biosynthesis in both cell populations was induced very strongly by
      transforming growth factor beta1 (TGFbeta1). Interleukin-1beta counteracted COMP
      induction by TGF-beta1. COMP was not detected in culture media of skin or fetal
      lung fibroblasts, either in the absence or the presence of TGFbeta1. COMP mRNA
      was also present in fresh synovial tissue specimens obtained from patients with
      RA. CONCLUSION: COMP is synthesized and secreted not only by articular
      chondrocytes, but also by synovial fibroblasts. The demonstration of COMP
      expression in surgical specimens of synovial tissues suggests that the inflamed
      synovium may provide an additional source for the elevated levels of COMP
      observed in arthritis. Thus, increased COMP levels in body fluids may be
      indicative of active synovitis as well as of accelerated joint erosion.

PMID- 9627010
TI  - Progressive polyarthritis induced in BALB/c mice by aggrecan from normal and
      osteoarthritic human cartilage.
AB  - OBJECTIVE: To find an "unlimited" source of antigenic material (aggrecan) for
      arthritis induction in BALB/c mice; to analyze the specificities of immune
      reactions to aggrecan and type II collagen in 2 arthritis-susceptible murine
      strains, BALB/c mice for proteoglycan (aggrecan)-induced arthritis and DBA/1j
      mice for collagen-induced arthritis; to compare the histopathologic features of
      arthritis induced by purified aggrecans or total extracts of osteoarthritic (OA)
      cartilage; and to determine arthritis susceptibility in various BALB/c colonies.
      METHODS: Aggrecans from total extracts of human fetal, normal adult, OA, and
      rheumatoid cartilage samples and from osteophytes were isolated, purified by
      gradient centrifugation, deglycosylated, characterized, and tested for arthritis
      induction. Purified type II collagen and salt-soluble collagens from OA cartilage
      were denatured, stromelysin treated, and used for immunization and arthritis
      induction in arthritis-susceptible (DBA/1j and BALB/c) murine strains. RESULTS:
      Chondrocytes from OA cartilage synthesize predominantly fetal-type aggrecan,
      which is the most efficient antigenic material for arthritis induction in BALB/c
      mice. The critical autoimmune/arthritogenic T cell epitopes of aggrecan are
      located in the G1 domain. Although most of the aggrecan molecules are heavily
      degraded and lost from OA cartilage, the G1 domain-containing fragments
      accumulate in OA cartilage. The amount of G1-containing fragments is
      approximately twice as much in OA than in normal adult articular cartilage, and
      the arthritogenic epitope(s) remains intact in G1-containing fragments retained
      in cartilage. Thus, total extracts of OA cartilage (without additional
      purification), if deglycosylated appropriately, can be used as arthritogenic
      material in BALB/c mice. CONCLUSION: Predominantly G1 domain-containing fragments
      of aggrecan accumulate in OA cartilage, and these are the fragments which induce
      arthritis in BALB/c mice. Arthritis induction is highly specific for aggrecan
      epitopes and dictated by the genetic background of the BALB/c strain.

PMID- 9627011
TI  - Cellular immunity to the G1 domain of cartilage proteoglycan aggrecan is enhanced
      in patients with rheumatoid arthritis but only after removal of keratan sulfate.
AB  - OBJECTIVE: To determine whether patients with rheumatoid arthritis (RA) express
      cellular immunity to the purified G1 globular domain of cartilage proteoglycan
      (PG) aggrecan and whether it is influenced by the removal of keratan sulfate (KS)
      chains from the molecule. METHODS: The G1 globular domain of PG was purified from
      mature bovine articular cartilage, digested with keratanase, and used in
      proliferation assays with peripheral blood lymphocytes (PBL) isolated from 43
      patients with RA, 11 patients with nonarticular rheumatism (NAR), including soft
      tissue rheumatism and mechanical back pain, and 13 healthy age- and sex-matched
      control subjects. RESULTS: Removal of KS chains from the G1 globular domain
      resulted in significantly increased prevalence and values of cellular immune
      responses to G1 in RA patients compared with the control and NAR groups. In the
      majority of RA patients, KS chains on G1 significantly inhibited its immune
      recognition by PBL. There was no significant effect of KS removal on the immunity
      to G1 in patients with NAR and in the healthy control group. CONCLUSION: These
      results reveal that immune reactivity to the G1 globular domain of the cartilage
      PG aggrecan is enhanced in patients with RA but only when KS chains are removed.
      Thus, KS chains inhibit immune responses to this domain of aggrecan. Since
      immunity to the G1 globular domain of aggrecan induces an erosive polyarthritis
      in BALB/c mice after removal of KS chains, immunity to the G1 globular domain,
      cleaved by proteases to remove KS chains, may play a role in the pathogenesis of
      RA.

PMID- 9627012
TI  - Human anticardiolipin monoclonal autoantibodies cause placental necrosis and
      fetal loss in BALB/c mice.
AB  - OBJECTIVE: To analyze the structure, specificity, and in vivo pathogenetic
      potential of 2 human anticardiolipin (aCL) monoclonal antibodies (MAb). METHODS:
      Human aCL IgG MAb were generated from hybridized Epstein-Barr virus-induced B
      cell lines from a healthy subject (MAb 519) and from a patient with primary
      antiphospholipid syndrome (MAb 516). Studies of antigen-binding specificity and
      analysis of Ig V-gene mutations were carried out. The MAb were independently
      injected into mated female BALB/c mice, and their effect on pregnancy outcome was
      compared with that of MAb 57, a highly mutated and antigen-selected human
      IgG1lambda rabies virus antibody. RESULTS: Both MAb 519 and MAb 516 utilized
      minimally mutated V(H)DJ(H) and VkappaJkappa gene segments and bound cardiolipin
      and other anionic phospholipids in the absence of beta2-glycoprotein I (beta2
      GPI). The mice injected with aCL MAb displayed a significantly higher rate of
      fetal resorption and a significant reduction in fetal and placental weight as
      compared with those injected with MAb 57. These findings were accompanied by a
      finding of placental human IgG deposition and necrosis in the aCL MAb-treated
      animals. CONCLUSION: The results of this study indicate that human aCL IgG that
      are beta2-GPI independent can induce pathology.

PMID- 9627013
TI  - Anti-Sm autoantibodies cross-react with ribosomal protein S10: a common
      structural unit shared by the small nuclear RNP proteins and the ribosomal
      protein.
AB  - OBJECTIVE: Cross-reactivity of anti-Sm autoantibodies with a certain ribosomal
      protein has been reported previously. The present study was undertaken to
      identify the anti-Sm-reactive ribosomal protein, and to characterize the cross
      reactive epitope. METHODS: Two-dimensional gel electrophoresis followed by
      immunoblotting was used to identify the ribosomal protein (S10) which was
      reactive with the Y12 anti-Sm monoclonal antibody (MAb). Human anti-Sm antibodies
      were also tested for cross-reactivity with the Sm-B/B', Sm-D, and isolated S10
      proteins by immunoblotting. Epitope analysis was performed by immunoprecipitation
      of in vitro-translated products of the recombinant S10 and its various mutants.
      RESULTS: The Y12 MAb and the affinity-purified human anti-Sm autoantibodies cross
      reacted with ribosomal S10 protein. Reactivity of the Y12 MAb with S10 protein
      was abolished by deletion of 19 amino acids at the carboxyl-terminus of S10,
      containing the Gly-Arg-Gly sequence motif shared by Sm-B/B' and Sm-D (D1 and D3).
      Replacements of Arg-158 with Gly and of Arg-158/Arg-160 with Gly/Gly at the
      carboxyl-terminal 157-Gly-Arg-Gly-Arg-Gly region disrupted the Y12 MAb
      recognition. CONCLUSION: At least a part of human anti-Sm antibodies and Y12 MAb
      show cross-reactivity among Sm-B/B', Sm-D, and ribosomal protein S10. The
      carboxyl-terminal Gly-Arg-Gly region of S10 protein is involved in constructing
      the cross-reactive epitope. This demonstrates that a common structural feature is
      shared by the ribosomal protein and the small nuclear RNP proteins.

PMID- 9627014
TI  - Molecular characterization of a CD95 signaling mutant.
AB  - OBJECTIVE: To study the intracellular signaling events associated with ligation
      of the surface receptor CD95. METHODS: A mutant clone of Jurkat T cells, DD3,
      which fails to transmit apoptotic signals through CD95, was selected for study.
      Surface expression of CD95 and the primary nucleotide sequence of CD95, as well
      as the functional effects of a mutant CD95 molecule found in DD3, were examined.
      RESULTS: DD3, while exhibiting impaired ability to undergo apoptosis after CD95
      ligation, retained the ability to die after ultraviolet light stimulation. A CD95
      complementary DNA (cDNA) cloned from DD3 encoded a mutant transmembrane protein
      lacking the carboxy-terminal "death domain." Western blotting confirmed the
      presence of both wild-type and mutant CD95 protein in DD3. Transfection of the
      mutant CD95 cDNA into parental Jurkat cells conferred protection from CD95
      mediated apoptosis. CONCLUSION: A mutant CD95 receptor lacking the cytoplasmic
      "death domain" can interfere with wild-type receptor function in T cells.

PMID- 9627015
TI  - Increased synovial endothelium binding and transendothelial migration of
      mononuclear cells during Salmonella infection.
AB  - OBJECTIVE: To investigate the adhesion and extravasation capacity of peripheral
      blood mononuclear cells (PBMC) and the transport of bacterial antigens within
      these cells during Salmonella infection. METHODS: Thirteen patients who were part
      of 2 outbreaks of Salmonella enteritidis infection were included in this study.
      The capacity of PBMC from these patients to bind to vascular endothelium in
      inflamed synovium was tested using a Stamper-Woodruff-type frozen-section assay.
      The same cells were studied for the presence of Salmonella antigens by
      immunofluorescence staining. The transendothelial migration of mononuclear cells
      containing Salmonella or its components through unstimulated endothelial cell
      layer was quantified. RESULTS: The capacity of PBMC to adhere to synovial vessels
      was significantly increased during Salmonella infection (P=0.0003). Monocytes had
      a transiently high adhesive state between 2 and 5 weeks after the patients had
      eaten the contaminated food. The cells containing Salmonella antigens were
      concentrated in the transmigrated population. CONCLUSION: During acute Salmonella
      infection the increased binding of PBMC to vascular endothelium in inflamed
      synovium and enhanced transmigration of PBMC containing Salmonella may be the key
      factors leading to transport of bacterial antigens through the endothelial
      barrier and initiation of arthritis in susceptible individuals.

PMID- 9627016
TI  - Evidence for a Mendelian gene in a segregation analysis of generalized
      radiographic osteoarthritis: the Framingham Study.
AB  - OBJECTIVE: To investigate the inheritance of generalized osteoarthritis (OA).
      METHODS: OA was identified on hand and knee radiographs obtained from members of
      the Framingham Study cohort (the parents) in 1967-1970 and 1992-1993, and from
      their adult children in the Framingham Offspring Study in 1993-1994. All hand and
      knee radiographs evaluated for OA were graded using the Kellgren and Lawrence
      (K/L) scale. A measure of generalized OA was defined as the count of the number
      of hand and knee joints affected, as determined by the proportion of joints with
      a K/L grade > or =2. The OA count, treated as a continuous variable, was adjusted
      for age, body mass index, and a measure of physical activity for each joint area
      (hand or knee). Calculations were made separately for each generation and each
      sex, and correlations were analyzed against the standardized residual of OA.
      Segregation analysis was used to test whether OA aggregated in families, and if
      its transmission fit a Mendelian pattern. RESULTS: A total of 337 nuclear
      families with 2 parents and at least 1 biologic offspring were studied. In
      parents, the mean age was 61.2 years at the time of hand radiographs and 72.8
      years at the time of knee radiographs, which were mostly obtained at a later
      examination. The mean age at the time of radiographs in offspring was 53.9 years.
      Using standardized residuals, parent-offspring and sibling-sibling correlations
      ranged from 0.115 to 0.306. In segregation analyses, models testing the
      hypotheses of no familial aggregation, no familial transmission, or a Mendelian
      gene alone were all rejected (P < 0.001 for each of these models). The best
      fitting models were mixed models with a Mendelian mode of inheritance and a
      residual multifactorial component. The Mendelian recessive model provided the
      best fit. CONCLUSION: These analyses support a significant genetic contribution
      to OA, with evidence for a major recessive gene and a multifactorial component,
      representing either polygenic or environmental factors.

PMID- 9627017
TI  - The long-term outcomes of rheumatoid arthritis: a 23-year prospective,
      longitudinal study of total joint replacement and its predictors in 1,600
      patients with rheumatoid arthritis.
AB  - OBJECTIVE: Although total joint arthroplasty (TJA) is a common procedure and an
      important outcome in rheumatoid arthritis (RA), little is known about its
      prevalence, failure rate, or predictors over the course of the illness. The
      current study evaluated these factors in 1,600 consecutive RA patients seen
      during a period of observation that extended 23 years. METHODS: Beginning in
      1974, data from 34,040 RA patient visits were entered prospectively into a
      computer databank. Data consisted of laboratory, radiographic, physical
      examination, and self-report questionnaires. At each assessment, we also noted a
      complete surgical history. Patients were also followed up by questionnaires that
      were mailed at 6-month intervals. RESULTS: Kaplan-Meier life-table estimates
      indicated that 25% of RA patients will undergo total joint arthroplasty (TJA)
      within 21.8 years of disease onset. For patients with 1 TJA, 25% had a TJA in a
      different joint within 0.92 years and 50% within 7.0 years. Ten years after TJA,
      approximately 6% of implanted knees and 4% of implanted hips had been replaced
      with a second TJA, and 12% and 13% of the joints had either a second TJA or a TJA
      related operation, respectively. In Cox regressions, a large series of clinical
      and laboratory variables, which primarily reflected disease activity, predicted
      TJA. Smoking, either past or present, had a protective effect. Patients with
      highly abnormal values on the Health Assessment Questionnaire Disability Scale,
      global severity, and erythrocyte sedimentation rate had a 3-6 times increased
      risk of TJA. CONCLUSION: TJA, a marker of joint failure and of RA outcome, is
      predicted by self-report assessments of severity and function, and by a series of
      laboratory, radiographic, and clinical variables. Prediction improves with the
      extent of observation, and 2-year observations approach full-study observations
      in their accuracy. Most TJAs survive for a long time in RA.

PMID- 9627018
TI  - Elevated levels of soluble interleukin-1 receptor type II and interleukin-1
      receptor antagonist in patients with chronic arthritis: correlations with markers
      of inflammation and joint destruction.
AB  - OBJECTIVE: To compare plasma levels of interleukin-1 receptor antagonist (IL
      1Ra), soluble IL-1 receptor type I (sIL-1RI), and soluble IL-1 receptor type II
      (sIL-1RII) in patients with chronic polyarthritis, and to establish correlations
      between levels of these naturally occurring IL-1 inhibitors and indices of
      disease activity and joint destruction. METHODS: Levels of IL-1Ra, sIL-1RI, and
      sIL-1RII were measured in plasma samples from patients with chronic
      polyarthritis, using specific radioimmunoassays. Levels were correlated with
      indices of disease activity and joint destruction. RESULTS: Plasma levels of IL
      1Ra, sIL-1RI, and sIL-1RII were significantly higher in polyarthritis patients
      than in controls. IL-1Ra levels correlated positively with all indices of disease
      activity and joint destruction (P < 0.0001). In contrast, sIL-1RII levels
      correlated negatively with indices of joint destruction, such as the Larsen score
      in the wrist (P < 0.04). Interestingly, sIL-1RII levels were higher in patients
      with nondestructive arthritis (Larsen score < or =1) than in patients with
      destructive arthritis. Levels of sIL-1RI did not correlate with indices of
      disease activity or joint destruction. CONCLUSION: The present findings indicate
      that increased levels of IL-1Ra, a natural antiinflammatory acute-phase protein,
      may reflect increased production and activity of IL-1. In contrast, endogenous
      sIL-1RII, unlike sIL-1RI, may constitute a natural antiinflammatory factor in
      chronic polyarthritis. These differences should be taken into account when these
      antiinflammatory molecules are considered as prognostic markers or for
      therapeutic use.

PMID- 9627019
TI  - Interleukin-10 promoter polymorphisms in Southern Chinese patients with systemic
      lupus erythematosus.
AB  - OBJECTIVE: To study the genetic association of interleukin-10 (IL-10) promoter
      polymorphisms in Southern Chinese patients with systemic lupus erythematosus
      (SLE), and to investigate possible associations with clinical manifestations of
      the disease. METHODS: DNA was extracted from 88 Chinese patients with SLE and 83
      ethnically matched controls. The IL-10 promoter region between positions -533 and
      -1120 was amplified by polymerase chain reaction, and polymorphisms were detected
      by restriction-enzyme cleavage. RESULTS: No significant difference in the allele
      or haplotype frequencies between SLE patients and controls could be demonstrated.
      The *A and *C alleles at the -597 position were linked to the *T and *C alleles
      at the -824 position, respectively. However, when clinical features were
      examined, the *A allele at the -597 position and the *T allele at the -824
      position were significantly associated with lupus nephritis, by chi-square
      analysis (P < 0.001, odds ratio 4.19, 95% confidence interval 2.02-8.71).
      Similarly, the haplotype -1087*A/-824*T/-597*A was also associated with renal
      involvement (P < 0.001, odds ratio 3.62, 95% confidence interval 1.80-7.31).
      CONCLUSION: IL-10 promoter polymorphisms are not strong determinants of
      susceptibility to the development of SLE, per se, in Southern Chinese
      individuals. However, IL-10 genotypes are strongly associated with certain
      clinical manifestations of SLE and may have a role in predicting disease
      prognosis.

PMID- 9627020
TI  - Poststreptococcal reactive arthritis: clinical characteristics and association
      with HLA-DR alleles.
AB  - OBJECTIVE: To assess the relationship of poststreptococcal reactive arthritis
      (ReA) to other forms of ReA and rheumatic fever by comparing the frequency of HLA
      B27 and DRB1 alleles in these diseases. METHODS: The diagnosis of
      poststreptococcal ReA was established in 25 children seen in a pediatric
      rheumatology clinic. HLA-B27 and DRB1 genotyping was performed in 18 of the white
      American patients. The DRB1 genotyping results were compared with those in 33
      patients with rheumatic fever and 190 normal individuals. RESULTS: HLA-B27 was
      positive in 3 of the 18 poststreptococcal ReA patients, a frequency not different
      from that found in normal individuals. Compared with normal controls, the
      frequency of the DRB1*01 allele was higher in poststreptococcal ReA patients
      (odds ratio [OR] 2.7, P=0.044), while DRB1*16 was increased in patients with
      rheumatic fever (OR 4.3, P=0.028). CONCLUSION: The association of
      poststreptococcal ReA with HLA-DRB1*01, but not with HLA-B27, suggests that its
      pathogenesis may be more similar to that of rheumatic fever than to that of ReA
      associated with enteric pathogens.

PMID- 9627021
TI  - Mortality studies in psoriatic arthritis: results from a single outpatient
      center. II. Prognostic indicators for death.
AB  - OBJECTIVE: To investigate prognostic factors associated with mortality in
      patients with psoriatic arthritis (PsA). METHODS: Patients followed up at the
      Toronto PsA Clinic between 1978 and 1994 were included. Patients were reviewed at
      initial clinic entry and at 6-month intervals using a standard protocol. Data on
      deaths were collected in a prospective manner, and death certificates were used
      to identify the primary and antecedent cause(s) of death. All death information
      was recorded in the clinic's computerized database. Only factors that represented
      standard clinical measures of disease activity and progression were studied. The
      relationship between potential prognostic factors recorded at the time of the
      first clinic visit and the mortality rate was determined using the Cox relative
      risk regression model. RESULTS: There were 428 patients (234 men and 194 women),
      of whom 68% were known to be alive on September 1, 1994, 20% were lost to
      followup but assumed to be alive, and 12% had died. Multivariate analysis
      revealed that an erythrocyte sedimentation rate (ESR) > 15 mm/hour, medications
      used prior to initial clinic visit, radiologic damage, and the absence of nail
      lesions were associated with an increased overall mortality rate. There is some
      suggestion that prior medication use was least important for deaths associated
      with the circulatory system, while radiologic damage was particularly important
      for such deaths. A marked sex-associated effect was noted among deaths caused by
      injuries/poisoning, since 6 of the deaths occurred in men and only 1 was in a
      woman. CONCLUSION: Patients with PsA are at an increased risk of death compared
      with the general population. Evidence of previously active and severe disease, as
      manifested by the prior use of medications and by radiologic changes as well as
      an elevated ESR at presentation, are prognostic indicators for death. The
      presence of nail lesions appears to be a protective factor that has the most
      clinical importance in the context of previously active and severe disease.

PMID- 9627022
TI  - Is occupational organic solvent exposure a risk factor for scleroderma?
AB  - OBJECTIVE: The primary objective was to determine whether occupational exposure
      to organic solvents is related to an increased risk of systemic sclerosis (SSc;
      scleroderma). METHODS: Occupational histories were obtained from 178 SSc patients
      and 200 controls. Exposure scores were computed for each individual using job
      exposure matrices, which were validated by an industrial expert. RESULTS: Among
      men, those with SSc were more likely than controls to have a high cumulative
      intensity score (odds ratio [OR] 2.9, 95% confidence interval [95% CI] 1.1-7.6)
      and a high maximum intensity score (OR 2.9, 95% CI 1.2-7.1) for any solvent
      exposure. They were also more likely than controls to have a high maximum
      intensity score for trichloroethylene exposure (OR 3.3, 95% CI 1.0-10.3). Among
      men and women, significant solvent-disease associations were observed among SSc
      patients who tested positive for the anti-Scl-70 autoantibody; these trends were
      not observed among the men and women who tested negative for anti-Scl-70.
      CONCLUSION: These results provide evidence that occupational solvent exposure may
      be associated with an increased risk of SSc.

PMID- 9627023
TI  - Reference centile charts for measures of disease activity, functional impairment,
      and metrology in ankylosing spondylitis.
AB  - OBJECTIVE: To construct reference centile charts for validated measures of
      disease activity, functional impairment, and metrology (the Bath Ankylosing
      Spondylitis Disease Activity Index [BASDAI], Bath Ankylosing Spondylitis
      Functional Index [BASFI], and Bath Ankylosing Spondylitis Metrology Index
      [BASMI]) in a population of patients with AS, and to explore the potential
      application of these charts in patient care and clinical research. METHODS: We
      collected BASDAI and BASFI data on 2,979 patients with AS from the Royal National
      Hospital for Rheumatic Diseases (RNHRD) database and BASMI data on 393 patients
      at RNHRD. Data on age, sex, and duration of AS were also obtained. Centile charts
      were constructed for the BASDAI, BASFI, and BASMI in both males and females, with
      duration of AS as the time-dependant variable. Where necessary, BASDAI, BASFI,
      and BASMI raw scores were transformed to ensure that the indices were normally
      distributed over the range of disease duration, and allowance was made for change
      in variability of the indices. RESULTS: Linear models were fitted to the mean and
      standard deviations of BASDAI, BASFI, and BASMI scores in males and females as a
      function of disease duration. A standard deviation score plot confirmed goodness
      of fit of the models, and fitted centiles were derived. Charts showing the 5th,
      10th, 25th, 50th, 75th, 90th, and 95th centiles were constructed. The charts
      confirmed that AS remains active after 40 years' duration (mean BASDAI score 2.22
      and 2.99 in males and females, respectively). The charts also demonstrated that
      females have greater disease activity and more functional impairment than males,
      despite better metrology. CONCLUSION: The use of centile reference charts for
      disease activity, functional impairment, and metrology in AS will allow
      physicians and patients to interpret index scores relative to a reference
      population and will provide the opportunity to assess change over time and
      response to therapeutic interventions, to improve definition of disease status,
      and to enhance patients' involvement in their care.

PMID- 9627024
TI  - Intravascular lymphoma presenting as symmetric polyarthritis.
AB  - Intravascular lymphoma (IVL) is an uncommon neoplastic disorder characterized by
      monoclonal intravascular expansion of lymphoid cells. Occlusion of small vessels
      in various organ systems probably accounts for the broad clinical spectrum of
      this type of lymphoma, which can closely mimic a variety of diseases, especially
      vasculitic disorders, and thus lead to delayed clinical diagnosis. This is the
      first report of a patient who presented with a predominant symptom of symmetric
      polyarthritis accompanied by fever. While her initial systemic symptoms, such as
      fever, improved rapidly after initiation of corticosteroid therapy, the response
      of the polyarthritic joint manifestations was only transient. The patient died of
      progressive lung involvement and was diagnosed as having IVL by histologic
      analysis of tissue samples obtained postmortem.

PMID- 9627025
TI  - Rheumatoid arthritis of the robust-reaction type.

PMID- 9627026
TI  - Cutaneous vasculitis as a paraneoplastic syndrome in adults.

PMID- 9627027
TI  - The delta32 deletion of CCR5 receptor in rheumatoid arthritis.

PMID- 9627028
TI  - Purity of synthetic ribosomal P peptides in enzyme-linked immunosorbent assay:
      comment on the article by Yoshio et al.

PMID- 9627029
TI  - Fibromyalgia: more questions and implications.

PMID- 9627030
TI  - Leishmaniasis mimicking new-onset juvenile dermatomyositis: comment on the
      article by Pachman et al.

PMID- 9627031
TI  - Does the choice of renal replacement therapy adversely affect the
      hypercoagulability associated with renal disease?
AB  - Both a bleeding diathesis and a tendency to hypercoagulability occur in the
      course of renal disease. More common and consistent in occurrence during the
      progression of renal failure to end-stage renal disease is the hemostatic defect.
      The principal cause of this abnormality is the uremic state and, as a rule, it is
      reversible following the institution of adequate renal replacement therapy and
      correction of the anemia with epoietin. By contrast, the tendency to
      hypercoagulability is usually encountered in patients with the nephrotic syndrome
      and shows a correlation to the degree of hypoalbuminemia, being more evident at
      serum albumin levels of < 2 g/dl. Although the coagulopathy is complex in
      pathogenesis, a defect in the fibrinolytic process plays a critical role in its
      development. A tendency to pro-thrombosis due to abnormal fibrinolysis has been
      identified also in patients on renal replacement therapy with continuous
      ambulatory peritoneal dialysis (CAPD). The observed coagulation abnormalities
      resemble those of the nephrotic syndrome. Although its etiology remains
      undefined, a role for the albumin losses in the peritoneal dialysate has been
      implicated in the prothrombotic state that occurs in some CAPD patients.

PMID- 9627032
TI  - Proteinuria and renal tubular damage: urinary N-acetyl-beta-D-glucosaminidase and
      isoenzymes in dissimilar renal disease.
AB  - Markers of renal tubular injury are difficult to interpret in patients with
      proteinura. The 24-hour urinary N-acetyl-beta-D-glucosaminidase (NAG)
      concentration was measured in 167 patients with dissimilar renal disease,
      function, and proteinuria. NAG isoenzymes were also separated in 69 patients,
      using a modified fast protein liquid chromatography technique. The 'A2' isoenzyme
      predominated at all levels of renal function and in all diagnostic groups.
      Urinary NAG and proteinuria were well correlated at all levels of renal function,
      as was NAG 'A2' isoenzyme. Proteinuria and urinary NAG were similarly correlated
      in patients with different glomerulonephritides, hypertensive nephrosclerosis,
      and chronic pyelonephritis, but not in those with diabetic nephropathy.

PMID- 9627033
TI  - Tissue-type plasminogen activator (tPA) and its inhibitor (PAI-1) in patients
      treated with continuous ambulatory peritoneal dialysis.
AB  - AIM: To establish whether the values of two key enzymes of fibrinolysis, tissue
      type plasminogen activator (tPA) and its inhibitor (PAI-1), differ between
      patients treated with continuous ambulatory peritoneal dialysis (CAPD) and
      healthy volunteers and whether plasma and dialysate tPA and PAI-1 values vary
      during one exchange of dialysis solution. METHODS: A total of 11 patients with
      chronic renal failure, treated with CAPD during the peritoneal equilibration test
      (in addition with blood sampling at time 0), and a control group of 11 healthy
      volunteers were examined. To identify the factors involved in the changes in tPA
      and PAI-1, 9 CAPD patients were subsequently monitored, in a crossover manner,
      during dialysis with solutions of 1.36 and 3.86% dextrose and off dialysis.
      RESULTS: Compared with healthy individuals, CAPD-treated patients showed a
      significantly lower tPA activity (0.39 vs. 0.81 IU/ml, p < 0.05). Changes in
      plasma fibrinolysis during one exchange of dialysis solution were characterized
      mainly by a decrease in PAI-1 concentrations and activities caused by the
      circadian rhythm of fibrinolysis. To explain, in the crossover part of the study,
      the values of plasma PAI-1 antigen at time 0 (07.00 h) and at time 2 (09.00 h)
      were 9.4 versus 6.5 ng/ml with the 1.36% solution (p < 0.05), 8.2 versus 4.9 with
      the 3.86% solution (p < 0.05), and 14.1 versus 9.1 ng/ml off dialysis (p < 0.01).
      Compared to baseline (0 ng/ml with 1.36 as well as 3.86% solutions), the levels
      of PAI-1 antigen in dialysis solution rose, apparently due to local production in
      the peritoneal cavity, to 0.5 ng/ml (p < 0.05) with the 1.36% solution, to 0.7 (p
      < 0.05) with the 3.86% solution after a 2-hour dwell time, and to 1.6 (p < 0.05)
      and 1.3 ng/ml (p < 0.05) after a 4-hour dwell time, respectively. Hence, the
      different dextrose levels in the dialysis solutions had no effect on the
      monitored parameters of fibrinolysis. CONCLUSION: The lower activity of plasma
      tPA, and the increase in PAI-1 levels in dialysis solutions may contribute to the
      development of thromboses in CAPD patients and to fibrin formation on the
      peritoneal surface with consequences such as peritoneal fibrosis.

PMID- 9627034
TI  - Timing of initiation of uremia therapy and survival in patients with progressive
      renal disease.
AB  - We conducted a prospective cohort study to detect any relationships between
      specific clinical features and laboratory indices at initiation of hemodialysis
      and long-term survival. One hundred and thirty-nine consecutive patients with
      chronic renal failure hospitalized to start maintenance hemodialysis between
      January 1990 and December 1994 were enrolled, and follow-up was completed through
      December 1995. At baseline, subjects were assigned to one of five groups based on
      their major indication for initiation of hemodialysis. The indications were: (a)
      nausea and vomiting; (b) severe weakness; (c) no major symptom (dialysis started
      because of 'high' serum creatinine and blood urea nitrogen concentrations); (d)
      volume overload, and (e) miscellaneous (angina, pericarditis, seizure, pruritus,
      and hyperkalemia). Blood urea nitrogen, serum creatinine and serum albumin
      concentrations were measured once before the first dialysis. The main outcome
      measure was death. The 139 study subjects included 77 women and 62 men comprising
      116 Blacks (83%), 15 Hispanics (11%), and 8 Whites (6%) of mean age 54 +/- 15
      years. Mean length of follow-up was 39 months. At baseline, mean blood urea
      nitrogen concentration was 121 +/- 38 mg/dl, mean serum creatinine concentration
      was 12.6 +/- 5.2 mg/dl, and mean serum albumin concentration was 3.5 +/- 0.62
      g/dl. Forty-two subjects (30%) died during follow-up. Cox regression analysis
      showed that there was no significant association between mortality and any of the
      indicators evaluated (indication for initiation of dialysis (p = 0.2), serum
      creatinine concentration (< 10 vs. > or = 10 mg/dl) (p = 0.8), blood ure nitrogen
      concentration (< 100 vs. > or = 100 mg/dl) (p = 0.68) and serum albumin
      concentration (< 4 vs. > or = 4 g/dl) (p = 0.62). All analyses included
      adjustment for age and diabetes. We conclude that in patients with chronic renal
      failure, the clinical features and laboratory indices used as guidelines for
      initiation of renal replacement therapy do not correlate with survival. Objective
      parameters that will permit initiation of dialysis at a time that will maximize
      survival in patients with chronic renal failure are needed.

PMID- 9627035
TI  - Lack of effect of gemfibrozil on cyclosporine blood concentrations in kidney
      transplanted patients.
AB  - Forty kidney-transplanted patients with hypertriglyceridemia, under treatment
      with cyclosporine alone or associated with other immunosuppressive drugs, were
      treated with gemfibrozil. This drug, for a long-term treatment (ranging from 4 to
      6 months), was able to decrease hypertriglyceridemia and did not modify either
      polyclonal (P) and monoclonal (M) cyclosporine blood levels or P/M ratio. These
      data seem to exclude an effect of gemfibrozil on cyclosporine blood
      concentrations. Therefore, the use of gemfibrozil in kidney-transplanted patients
      does not require modifications of cyclosporine dose.

PMID- 9627036
TI  - Atrial natriuretic peptide increases urodilatin in the circulation.
AB  - BACKGROUND: Urodilatin is a 32-amino-acid (AA) peptide formed in the kidney.
      METHODS: High-performance gel permeation chromatography and high-pressure liquid
      chromatography evaluation of plasma followed by sensitive urodilatin and atrial
      natriuretic peptide (ANP) assays revealed that urodilatin does circulate
      distinctly from ANP. RESULTS: Urodilatin circulates at very low levels (i.e 9-12
      pg/ml). Infusion of ANP increased the circulating concentration of urodilatin 135
      fold (p < 0.001), suggesting that some of the effects of ANP may be mediated by
      urodilatin while long-acting natriuretic peptide, vessel dilator, and kaliuretic
      peptide did not affect urodilatin in healthy humans (n = 30). Only ANP decreased
      the renal clearance of urodilatin (60-75%, p < 0.01). Urodilatin was metabolized
      into peptides smaller than 5 AAs as well as excreted intact into urine.
      CONCLUSION: Urodilatin circulates and is increased by ANP in humans.

PMID- 9627037
TI  - Nephrotic syndrome associated with diffuse mesangial hypercellularity: is it a
      heterogeneous disease entity?
AB  - Diffuse mesangial hypercellularity (DMH) is a rare primary mesangial
      proliferative glomerulonephritis associated with idiopathic nephrotic syndrome
      (INS). We conducted this study on 15 patients, including 5 patients with repeated
      specimens, with a follow-up of 0.9-17.5 years and evaluated the clinical course
      and pathological findings. Seven patients were male. Ten patients were under 14
      years of age. All specimens had INS and were diagnosed morphologically with
      primary diffuse mesangial proliferative glomerulonephritis at initial biopsy; 4
      were diagnosed with focal segmental glomerulosclerosis (FSGS) within 3 years by
      the second biopsy. The remaining 11 patients included 8 initial responders and 3
      initial nonresponders to 8 weeks' steroid therapy and had the histologic variant
      of the minimal-change nephrotic syndrome (MCNS). Ten of the 11 patients had
      normal renal function during the investigation period. One patient with the MCNS
      variant who was refractory to steroid therapy developed end-stage renal disease
      (ESRD) within 6 years. Four patient with the histologic variant of FSGS included
      1 initial responder, 2 late responders, and 1 steroid-refractory case. One
      patient with the FSGS variant developed ESRD within 4 years. The follow-up
      biopsies documented that the severity of mesangial hypercellularity was
      associated with the severity of proteinuria or hematuria. We conclude that DMH
      may be divided into heterogeneous disease entities, whereas morphologic changes
      in initial biopsies were similar. Each variant as well as the degree of DMH
      should be recognized routinely by follow-up biopsy, because they are prognostic
      indicators.

PMID- 9627038
TI  - Ischemic nephropathy in an elderly nephrologic and hypertensive population.
AB  - BACKGROUND: Atherosclerotic renovascular disease is a frequent cause of end-stage
      renal failure leading to dialysis in the elderly population. Its prevalence is
      known from autopsy or retrospective arteriographic investigations. This
      prospective study was conducted in 133 subjects with the inclusion criteria of
      hypertension and/or chronic renal failure starting after 50 years of age. Renal
      failure was unrelated to other known causes of renal disease. METHODS: The
      patients were subjected to echo-color doppler ultrasonography of renal arteries
      (104) and/or to renal scintigraphy (112). Thirteen of 27 patients with positivity
      using one or both noninvasive techniques were subjected to digital selective
      angiography. RESULTS: All the patients with positivity of echo-color doppler
      technique were true positives, with a consequent predictive value reaching 100%.
      Renal scintigraphy was of markedly lower predictive value. Based on the echo
      color doppler investigation, percentage positivity for hemodynamically
      significant stenosis (> 50%) was 3.2 (16.3% had mild nonsignificant stenosis of
      renal arteries) in the 50- to 59-year-old group, 20% (plus 12.5% with
      nonsignificant stenosis) in the 60- to 69-year-old group and 25% (plus 17.8%
      nonsignificant stenosis) in the > 70-year age group. Patients with significant
      stenosis also had a significantly higher degree of renal insufficiency and
      received a higher number of hypotensive drugs (p < 0.013). The percentage of
      hypertensive patients was not different in the stenotic and nonstenotic groups.
      CONCLUSIONS: A large percentage of the elderly population is affected by renal
      vascular obstructive disease and is at risk of developing end-stage renal
      failure. Considering the wide number of cases with foreseeable renal arterial
      stenosis in the vast population meeting the selection criteria, it is possible to
      conclude that not all cases evolve to renal failure due to different rates of
      progression or to untimely nonrenal death.

PMID- 9627039
TI  - Removal of serum beta-2 microglobulin using high-performance membranes and
      analysis of changes in serum BMG levels after dialysis.
AB  - BACKGROUND/AIMS: The present study was undertaken to analyze the beta2
      microglobulin (BMG)-removing efficiency of high-performance membranes (HPMs) in
      relation to changes in serum BMG levels after dialysis. METHODS: In 10 stable
      dialysis patients, six different HPMs were used in a crossover method. Serum BMG
      levels were measured immediately before dialysis, immediately after, 4 h after,
      and immediately before the next dialysis. On the basis of these measurements, the
      BMG removal rate was calculated. RESULTS: The BMG removal rate as calculated on
      the basis of the BMG level immediately after dialysis was 11.29% higher than the
      rate calculated on the basis of the BMG level 4 h after dialysis. CONCLUSION: The
      BMG removal rate can be overestimated if it is calculated on the basis of the BMG
      level immediately after dialysis.

PMID- 9627040
TI  - Free circulating magnesium and renal magnesium handling during acute metabolic
      acidosis in humans.
AB  - Ion-selective electrodes have been designed for determining the ionized
      concentration of magnesium in blood, the biologically active form of this ion.
      The effect of acute acidosis induced by ammonium loading on circulating and
      urinary magnesium was investigated in 11 volunteers. No changes in plasma total
      and ionized magnesium were noted following administration of ammonium chloride.
      On the contrary, administration of ammonium chloride increased the plasma free
      magnesium fraction and the urinary magnesium excretion. The study demonstrates
      that the hypermagnesiuria induced by acute acidosis is not caused by ionized
      hypermagnesemia and supports the theory that acidosis decreases the circulating
      magnesium fraction that is bound to proteins.

PMID- 9627041
TI  - Unusual cause of early graft dysfunction after kidney transplantation.
AB  - BACKGROUND/AIMS: Transplant renal artery stenosis usually develops in the later
      period after renal transplantation and is usually due to atherosclerosis and
      fibrosis at the anastomosis. A kinking renal artery stenosis, however, is a rare
      cause of early graft dysfunction. METHODS: In a 34-year-old-man early graft
      failure developed within 1 week after kidney transplantation. In the presence of
      histologically proven ischemic damage an arterial kinking stenosis was diagnosed
      by color Doppler sonography. Selective arteriography confirmed the sharp kinking
      of the transplant renal artery; however, a significant stenosis could not be
      visualized by arteriography. RESULTS: Due to progressive loss of renal function
      surgical resection of scar tissue in the kink of the transplant artery and
      nephropexy was performed. Immediately thereafter graft function and blood
      pressure significantly improved so that the successful clinical outcome of this
      unusual case of early graft failure confirmed the relevance of the arterial
      kinking stenosis. CONCLUSIONS: In this unusual case of early graft dysfunction
      relevant kinking renal artery stenosis could not be adequately visualized by
      arteriography, although color Doppler sonography clearly demonstrated the
      stenosis. Therefore, both methods should be considered if parenchymal causes of
      graft dysfunction are excluded by biopsy and a kinking renal artery stenosis is
      suspected.

PMID- 9627042
TI  - Uremic optic neuropathy. A uremic manifestation mandating dialysis.
AB  - A 41-year-old male patient in end-stage renal failure presented on two occasions,
      over an 18-month period, with painless unilateral visual deterioration and optic
      disc edema. Clinical findings were compatible with a diagnosis of uremic optic
      neuropathy. On his initial presentation, the patient refused the onset of
      dialysis, resulting in a permanent visual deficit of the left eye. On his
      subsequent admission with a similar clinical picture, this time of the right eye,
      dialysis combined with corticosteroid therapy was promptly instituted. This led
      to a rapid improvement of the visual acuity and visual field defects of the right
      eye concomitant with subsidence of the edema of the optic nerve head.

PMID- 9627043
TI  - Immunoallergic granulomatous interstitial nephritis following treatment with
      omeprazole.
AB  - A 69-year-old male who had a long history of ocular myasthenia was treated with
      omeprazole for 3 months. Progressive renal insufficiency was discovered
      fortuitously. There were no clinical or laboratory manifestations of
      immunoallergy. Renal biopsy revealed severe granulomatous interstitial nephritis,
      tubular injury and fibrosis. Histology of a liver nodule disclosed hepatic
      granulomatous involvement. Withdrawal of omeprazole and a short course of
      corticosteroids were followed by improvement but not normalization of renal
      function. This is the eighth report of omeprazole-induced interstitial nephritis.
      In the present case as in 2 others in the literature, the patients had been
      followed up for an autoimmune disease previously, which suggests that in patients
      with such a background, patients should be examined regularly for renal
      functional impairment during treatment with omeprazole.

PMID- 9627044
TI  - A case of multicentric Castleman's disease associated with renal amyloidosis and
      pure red cell aplasia.
AB  - This is the first reported case of multicentric Castleman's disease (MCD)
      associated with renal amyloidosis and pure red cell aplasia (PRCA). Inguinal
      lymph node biopsy showed follicular hyperplasia with prominent germinal centers
      and plasma cell proliferation in the interfollicular areas. Renal biopsy
      specimens revealed intraglomerular amyloid deposits, defined as AA amyloidosis.
      Since amyloid deposits were not present in the gastric and rectal mucosal
      tissues, his renal disorder was found to be an unusual secondary amyloidosis
      associated with MCD. Following treatment by plasma exchange, there was
      progressive deterioration of anemia due to PRCA detected by bone marrow
      aspiration. Subsequently he was successfully treated with steroid pulse therapy
      not only for anemia but also for renal function.

PMID- 9627045
TI  - Hyporeninemic hypoaldosteronism in patients with nephrotic syndrome.
AB  - Five nephrotic patients, who did not present sodium retention when on sodium
      balance, have been studied. All had membranous nephropathy, were normotensive and
      renal function was normal in 2 and slightly reduced in 3. The following
      parameters were measured: 24-hour excretion of aldosterone, the response of
      plasma renin activity (PRA) and of plasma aldosterone to upright posture,
      postural changes of the fractional excretion of sodium and lithium, and
      natriuretic response to spironolactone. The resting values of plasma aldosterone
      were low in all patients, and after stimulation by upright posture they increased
      hardly to the low-normal limit only in 1 patient. Resting PRA was normal in all
      patients and increased slightly, after stimulation. The 24-hour urinary excretion
      of aldosterone was low in 4 patients and borderline in 1. No natriuretic response
      to spironolactone was observed in any patients. After upright posture the
      fractional excretions of sodium and lithium decreased significantly and to the
      same extent in all patients. Four nephrotic patients with fluctuating,
      spontaneous episodes of sodium retention and of sodium excretion have been
      studied as controls. These patients had normal values of urinary aldosterone and
      of resting PRA and aldosterone. After upright posture the changes of PRA and of
      aldosterone were clearly evident in 2, and exaggerated in the other 2 patients.
      In these patients, a significant increase of sodium excretion occurred after
      treatment with spironolactone. These results suggest that a not negligible number
      of patients with nephrotic syndrome have hyporeninemic hypoaldosteronism. This
      diagnosis should be taken into account when investigating the role of aldosterone
      in sodium retention in nephrotic syndrome.

PMID- 9627046
TI  - Crescentic glomerulonephritis in a patient with relapsing nodular panniculitis.

PMID- 9627047
TI  - Pasteurella multocida peritonitis following cat bite of peritoneal dialysis
      tubing. With a brief review of the literature.

PMID- 9627048
TI  - Aggressive treatment of HIV-associated microangiopathic haemolytic anaemia is
      associated with good outcome.

PMID- 9627049
TI  - Control of severe proteinuria with losartan after renal transplantation.

PMID- 9627051
TI  - Differential expression of alpha2,6-sialyltransferase in colon tumors recognized
      by a monoclonal antibody.
AB  - It has been reported that alpha2,6-sialyltransferase (alpha2,6-ST; E.C. 2.4.99.1)
      activity is associated with cellular differentiation. To define its role in colon
      carcinoma differentiation, we have generated murine monoclonal antibodies (MAb)
      against alpha2,6-sialyltransferase. The MAb, designated 6B9 of IgM isotype,
      showed strong reactivity with the purified and crude alpha2,6-ST by ELISA and dot
      blot assays. Western blotting with MAb 6B9 identified purified alpha2,6-ST of MW
      47 kDa and the same MW protein from rat and human liver extracts. The MAb also
      reacted with two other liver proteins of approximate MW 65 and 100 kDa.
      Immunoperoxidase studies with formalin-fixed paraffin-embedded tissues showed
      that MAb 6B9 reacts with liver tissues, the staining of hepatocytes was granular
      and cytoplasmic. There was a distinct pattern of zonal distribution of this
      enzyme in hepatocytes located particularly in the portal areas of the liver
      corresponding to zone 1. Normal colon (100%) and hyperplastic polyps (100%)
      showed very weak to no reactivity. Adenomas (100%) demonstrated moderate
      reactivity, while the poor (33%), moderate (100%) and well-differentiated (80%)
      colon adenocarcinomas showed strong reactivity. Results suggest that alpha2,6-ST
      is associated with the differentiation state of colon tumors.

PMID- 9627050
TI  - Expression analysis of the soluble and membrane-associated forms of the
      interleukin-1 receptor-related T1 protein in primary mast cells and fibroblasts.
AB  - The murine T1 gene encodes a membrane-bound glycoprotein (T1M) and a soluble
      variant (T1S) which represents the ectodomain of the receptor-type form. T1 is an
      orphan receptor belonging to the interleukin-1 receptor family. Its biological
      function is currently unknown. We analyze the expression of the two T1 proteins
      in mast cells and fibroblasts by using a set of monoclonal antibodies (MAb) that
      specifically recognize the extracellular portion of the T1 receptor. To generate
      anti-T1 MAbs, we immunized Lewis rats with a eukaryotically expressed chimeric
      protein consisting of the T1-receptor ectodomain fused to a human immunoglobulin
      domain. The two MAbs DJ4 and DJ8 were shown to specifically detect the murine T1M
      protein on the surface of primary IL-3-dependent bone marrow-derived mast cells
      as shown by flow cytometry and immunohistochemistry. Both antibodies were also
      capable of immunoprecipitating the membrane-associated 110-120 kDa T1M protein
      from mast cell lysates. In serum-stimulated but not in quiescent NIH3T3
      fibroblasts, DJ4 and DJ8 MAbs detected both the soluble T1S protein as a 45-65
      kDa band on SDS polyacrylamide gels as well as the membrane-bound 95 kDa T1M
      protein. The T1M protein in fibroblasts was less abundantly expressed and
      exhibited a lower molecular weight than the mast cell-produced T1M, probably as a
      consequence of different protein glycosylation. The MAbs described here represent
      highly specific reagents and valuable tools that should facilitate the
      establishment of the murine T1 protein expression pattern thus contributing to
      the solution of the question of its function.

PMID- 9627052
TI  - New anti-Cu-TETA and anti-Y-DOTA monoclonal antibodies for potential use in the
      pre-targeted delivery of radiopharmaceuticals to tumor.
AB  - Monoclonal antibodies were raised against yttrium(III)-1, 4, 7, 10
      tetraazacyclododecane-N,N',N''N'''--tetraacetic acid (Y-DOTA) and copper(II)-1,
      4, 8, 11-tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid (Cu-TETA). Four
      hybridomas with high Y-DOTA binding activity and one hybridoma with Cu-TETA
      activity were selected. MAbs were purified from mouse ascites by Protein A
      affinity chromatography and characterized. Affinity constants were determined by
      equilibrium dialysis and the highest affinity Y-DOTA MAb (K(aff) = 1.9 x 10(8) M(
      1)) was further characterized by competitive ELISA. Gd-DOTA competed as well as Y
      DOTA, whereas In-DOTA required 740x higher concentrations for 50% inhibition of
      this Y-DOTA MAb binding to human serum albumin-Y-DOTA-coated microtiter plates.
      These anti-metal chelate MAbs have potential use as vehicles for the pretargeted
      delivery of radiometal chelates to tumors.

PMID- 9627053
TI  - Characterization of human IgG1 monoclonal antibody against gangliosides expressed
      on tumor cells.
AB  - A human IgG1.k monoclonal antibody (MAb) designated GMA1 was developed by fusing
      pooled lymph node lymphocytes from cancer patients with the human lymphoblastoid
      cell line, SHFP-1. The GMA1 MAb reacted with several melanoma and neuroblastoma
      cell lines. Normal tissue derived from human brain and tumor-cell lines derived
      from colon, ovary, and breast were not reactive. FACS analysis performed using
      live cells demonstrated that the antibody recognizes a cell-surface antigen.
      Enzyme immunoassay (EIA) and thin layer chromatography (TLC) immunostaining with
      purified gangliosides indicated that the antibody has specificity for the major
      tumor associated gangliosides GD3, GM3, and GD2. GMA1 heavy and light chain genes
      were isolated by RT-PCR and a recombinant derivative of this human antibody was
      expressed in Chinese hamster ovary (CHO) cells. High-level antibody synthesis and
      secretion was achieved using a vector designed to maximize expression. FACS
      analysis and TLC immunostaining indicated recombinant GMA1 reacted with human
      tumor cell lines and gangliosides GD3, GM3, GD2 in a manner similar to the
      antibody produced by the hybridoma cell line, demonstrating that the specificity
      of the antibody was not altered during molecular cloning.

PMID- 9627054
TI  - Development and characterization of a murine monoclonal antibody reactive with a
      64 kDa somatic antigen of Burkholderia cepacia.
AB  - Monoclonal antibodies (MAbs) to Burkholderia cepacia were produced from mice
      immunized with inactivated whole-cell antigen. For screening of resulting MAbs an
      enzyme-linked immunosorbent assay (ELISA) was used. A stable hybridoma cell line
      (BC-2) producing specific antibodies to a 64 kDa somatic antigen from B. cepacia
      was established. In ELISA and immunoblotting analysis the MAb BC-2 recognized all
      tested strains of B. cepacia whereas no cross-reaction with 32 Pseudomonas
      aeruginosa strains was found. From a wide range of other bacteria only strains of
      the species Burkholderia mallei, Burkholderia pseudomallei, and Burkholderia
      gladioli showed cross-reactions. The MAb BC-2 will be used to develop a
      diagnostic assay for the identification of B. cepacia and B. gladioli, important
      agents of nosocomial infections in immunocompromised patients suffering
      especially from cystic fibrosis (CF).

PMID- 9627055
TI  - Generation of a recombinant bacteriophage antibody library to mycobacterium
      tuberculosis.
AB  - Monoclonal antibodies to Mycobacterium tuberculosis (Mtb) may be useful for
      laboratory diagnosis, antigenic characterization, and studying the immune
      response to infection and vaccination. To investigate the potential of the
      recombinant phage antibody technique for the isolation of single-chain fragments
      (ScFv) reactive with Mtb culture proteins, we generated a bacteriophage antibody
      library from splenic tissue of mice immunized with heat-killed Mtb. Heavy- and
      light-chain immunoglobulin genes were isolated and amplified by the polymerase
      chain reaction (PCR), and the products were assembled into ScFv gene fragments
      and cloned into the pCANTAB5-E phagemid. Phagemids were introduced into E. coli
      TG1 by electrotransformation, followed by rescue of antibody-expressing phage
      using M13K07 helper-phage superinfection. Immunoselection of the Mtb phage
      library against Mtb cell wall extract or culture filtrate proteins selected
      antigen-specific and cross-reactive phage antibodies, none of which demonstrated
      reactivity to the immunodominant 65-kDa Mtb antigen. These results suggest that
      the phage antibody system has the potential to generate a diverse population of
      the reactive phage that may prove useful for investigating the immune response to
      Mtb infection and vaccination.

PMID- 9627056
TI  - A monoclonal antibody against the X protein of hepatitis B virus: fine mapping of
      its epitope and application in a quantitative ELISA of the X protein in sera of
      hepatitis B patients.
AB  - A HBx-specific mouse monoclonal antibody was developed and its epitope mapped to
      a hydrophilic segment 94HKRTLGL100 using the multipin peptide synthesis
      technique. A sensitive ELISA with a threshold of 5 to 10 ng was developed to
      identify the HBx-positive hepatitis B cases and measure the levels of HBx in
      sera. The same patient sera were also analyzed for the presence of anti-HBx using
      the purified recombinant antigen. HBx was present in 23% of the cases (15/65)
      whereas only 14% of the cases (9/65) were positive for anti-HBx. The mean value
      of HBx in acute hepatitis sera was higher (522 ng/ml) than in cirrhosis cases (48
      ng/ml). PCR amplification of the S gene showed that all 15 HBx-positive cases
      were also positive for the viral DNA.

PMID- 9627057
TI  - Development and characterization of monoclonal antibody to T-antigen: (gal beta1
      3GalNAc-alpha-O).
AB  - The saccharide antigen, Gal beta1-3GalNAc or T antigen, is of biologic importance
      in many systems. It is a tumor-associated carbohydrate antigen, a temporally
      expressed antigen in germinal center B cells and cortical T cells, a parasite
      associated antigen, a spermatozoa vitality marker and an antigen on aged red
      blood cells. It may play a role in normal cellular adhesion and in tumor cell
      metastasis. Well characterized monoclonal antibodies (MAb) to Gal beta1-3GalNAc
      will be useful for further studies in these areas. We developed an IgG3 MAb to
      Gal beta1-3GalNAc by immunizing the mice with a synthetic Gal beta1-3GalNAc-BSA
      conjugate. The MAb was analyzed using inhibition enzyme immunoassays with related
      synthetically prepared sugars to determine the restrictions involved in the
      antibody binding. Use of synthetic sugars as competitors enabled us to delineate
      the epitope restrictions on the binding activity of this monoclonal and will
      enable use of this MAb in studies concerning the biologic importance of this
      disaccharide.

PMID- 9627058
TI  - Production and characterization of monoclonal antibodies to the catenin p120ctn.
AB  - This report describes the generation and characterization of a panel of
      monoclonal antibodies (MAb) to the catenin p120ctn. p120ctn (formerly p120cas) is
      a cadherin-binding protein with structural similarity to the classical catenins
      beta-catenin and plakoglobin. It was originally identified as a prominent Src
      substrate and subsequently as a substrate for the Platelet Derived Growth Factor
      (PDGF), Epidermal Growth Factor (EGF), and Colony Stimulating Factor-1 (CSF-1)
      receptor tyrosine kinases. To facilitate further study of p120 function, we have
      generated novel MAbs to both the N- and C-terminal ends of p120 and compared them
      to previously described antibodies to these regions.

PMID- 9627059
TI  - An anti-human VEGF monoclonal antibody, MV833, that exhibits potent anti-tumor
      activity in vivo.
AB  - Vascular endothelial growth factor (VEGF) is a potent angiogenic factor for tumor
      angiogenesis and growth. We previously established the immunoneutralizing
      monoclonal antibodies (MAbs) to human VEGF, and showed that MV101 (IgG1) and
      MV303 (IgG2a) inhibited the growth of human solid tumor xenografts in nude mice.
      Then, we tried to develop another immunoneutralizing anti-VEGF MAb that exhibited
      more potent antitumor activity than MV101 or MV303. We obtained more than 140
      clones of hybridomas that were producing anti-VEGF MAb from the mice immunized
      with recombinant human VEGF121. Among them, 26 clones showed the
      immunoneutralizing activity and MV833 possessed the most potent antitumor
      activity in vivo. A total of 9 i.p. administrations of 25 microg of MV833
      inhibited the growth of human fibrosarcoma HT-1080 solid tumor xenografted in
      nude mice more potently than MV101 or MV303. Moreover, only 1 i.v. administration
      of 100 microg of MV833 on Day 1 after tumor inoculation also significantly
      inhibited the growth of HT-1080 in vivo, whereas MV101 and MV303 did not. All
      three MAbs inhibited the growth of human umbilical vein endothelial cells (HUVEC)
      induced by VEGF121 and the binding of 125I-labeled VEGF121 to HUVEC to a similar
      extent. The binding of MV101 and MV303 to VEGF121 was cross-competitive; however,
      MV833 weakly competed with the binding of MV101 to VEGF121. These findings
      indicated that MV833 recognized the region(s) of VEGF differently than MV101 or
      MV303, and this difference contributed to the superiority of antitumor activity
      of MV833.

PMID- 9627061
TI  - Efficient purification of mouse anti-FGF receptor IgM monoclonal antibody by
      magnetic beads.
AB  - Affinity chromatography has been widely used for the purification of monoclonal
      antibodies (MAb). Traditionally, activated agarose beads conjugated with specific
      antisera have been used as a solid support in chromatographic protein
      purification. Magnetic beads conjugated with various antibodies have recently
      become an alternative method for the isolation of diverse proteins, nucleic
      acids, and cell types. In this study, murine anti-fibroblast growth factor
      receptor 1 (FGFR1) immunoglobulin M (IgM) was isolated from protein solutions to
      compare immunoaffinity column chromatography and magnetic bead IgM purification
      methods. Using immobilized rat anti-mouse IgM MAb, an UltraLink 1-ethyl-3-(3
      dimethylaminopropyl)carboiimide (EDC)/diaminodipropylamine (DADPA) immunoaffinity
      column and polystyrene-coated magnetic beads were used for the purification of
      mouse IgM from bovine serum albumin/phosphate-buffered saline (BSA/PBS) as well
      as from crude ascites. Protein quantitation and percent IgM yield were determined
      by reducing SDS-PAGE electrophoresis followed by silver staining, then IgM and
      protein contaminants were quantitated using densitometry analysis. IgM anti-FGFR1
      binding specificity and immunologic activity were determined by enzyme-linked
      immunosorbant assay (ELISA). This study demonstrates that magnetic bead isolation
      of IgM from ascites is more effective than traditional affinity chromatography
      purification as determined by greater IgM yield, purity, and immunologic
      activity.

PMID- 9627060
TI  - Characterization of monoclonal antibodies directed to the amino-terminus of the
      WT1, Wilms' tumor suppressor protein.
AB  - We have produced and characterized three monoclonal antibodies (MAbs) directed to
      the amino terminus of the WT1 Wilms' tumor suppressor transcription factor and
      compared their properties to rabbit polyclonal sera raised to the same immunogen.
      A recombinant protein consisting of amino acids 1-181 of human WT1 was
      overexpressed in E. coli, purified, and used as the immunogen. Three MAbs
      designated 6F-H2, 6F-H7, and 6F-HC-17--all of the IgG1 subclass--were selected
      and further characterized. Each recognized all isoforms of the full-length WT1
      protein in Western blot assays and immunoprecipitated WT1 in both physiologic
      buffers and under high detergent/high salt (RIPA) conditions. Preliminary epitope
      mapping suggests that all three MAbs recognize a region in the amino terminal 84
      amino acids of WT1 and that the MAbs do not recognize the polyglycine or
      polyproline regions of the protein. The WT1 antibodies do not recognize the
      structurally and functionally related early growth response (EGR)1, EGR2, EGR3,
      or EGR4 proteins. All WT1 MAbs recognize the murine WT1 protein and
      immunohistochemical staining of murine embryonic and newborn kidney sections show
      strong staining of condensing metanephric mesenchyme and primitive podocytes in
      developing glomeruli. These WT1-specific MAbs should be useful in characterizing
      the biochemical and developmental roles of WT1 and in defining the emerging role
      of WT1 as a diagnostic and/or prognostic marker in mesothelioma, leukemias, and
      breast cancer.

PMID- 9627062
TI  - Screening of hybridoma clones producing antibodies against plasma membrane
      associated materials.
AB  - We have developed a novel method for screening hybridoma clones producing
      antibodies against plasma membrane-associated materials. The method is based on
      the binding of cells by antigen-antibody complex formation to immobilized
      antibodies. The monoclonal antibodies (MAbs) were trapped by goat anti-mouse
      immunoglobulin antibodies, which were coated on the surface of 96-well plastic
      plates. Cells to be tested were then added to these plates and the number of
      bound cells was quantified by the activity of phosphatase of bound cells. This
      method allows quick and reliable screening of hybridoma clones without resorting
      to the use of expensive instruments such as a flow cytometer. We immunized mice
      with two different kinds of cells and obtained two interesting but contrasting
      MAbs reacting to cell-surface antigens: one interacts quite specifically with
      neuroblastoma cells and the other reacts equally with various cells with the
      exception of GOTO, a neuroblastoma cell.

PMID- 9627063
TI  - Utstein style--a suggestion for revision: a statement by the Helsinki Cardiac
      Arrest Research Team.

PMID- 9627064
TI  - Epidemiology and survival rate of out-of-hospital cardiac arrest in north-east
      Italy: The F.A.C.S. study. Friuli Venezia Giulia Cardiac Arrest Cooperative
      Study.
AB  - The results of the first epidemiological, prospective, multicentric study on
      cardiac arrest in a geographical Italian region are reported. On 708 consecutive
      cardiac arrests, 438 underwent cardiopulmonary resuscitation (CPR). Of these, 344
      were identified of cardiac aetiology. The underlying initial rhythm was: 166
      asystole (48.3%), 104 ventricular fibrillation (30.2%), 74 pulseless electrical
      activity (21.5%). The best outcome occurred in patients whose cardiac arrest was
      witnessed by the EMS (49% return of spontaneous circulation (ROSC), 21% hospital
      discharge). When cardiac arrest was witnessed by lay people, 20.5% had ROSC and
      4.4% were discharged alive from the hospital. When it was unwitnessed ROSC and
      hospital discharge were 8.6 and 1.7%, respectively. Ventricular fibrillation was
      highly predictive of outcome. Both ROSC and hospital discharge correlated
      inversely with the delay of the first defibrillation. Overall, the highest
      probability of survival was achieved when CPR interventions were started within
      the first minutes after collapse. Basic Life Support (BLS) manoeuvres began after
      9 min of untreated cardiac arrest were still followed by a ROSC, but none of
      these patients survived. The incidence of prehospital cardiac arrest in our
      population was estimated to be in proportion of 0.95/1000 per year with a
      survival rate of 6.7%.

PMID- 9627065
TI  - Theoretical calculation of maximum attainable benefit of public access
      defibrillation in Belgium. Belgian Cardio Pulmonary Cerebral Resuscitation Study
      Group.
AB  - OBJECTIVE: Assuming that a lay person performing cardiopulmonary resuscitation
      (CPR) will also use an automatic external defibrillator (AED) wherever available,
      we tried to estimate the maximal attainable benefit of public access
      defibrillation in some centres in Belgium. METHODS: We analysed retrospectively
      the data from the Belgian Cardio Pulmonary Cerebral Resuscitation Registry
      collected between 1991 and June 1996. The majority of these emergency medical
      service (EMS) systems are two-tiered with an early defibrillation program for the
      first tier and a physician-staffed second tier. RESULTS: The data show that, in
      5543 registered cases, there were 1001 (18%) adults with non-traumatic
      ventricular fibrillation/ventricular tachycardia (VF/VT) as the first monitored
      rhythm. In this subgroup there were 419 (42%) cases who had lay CPR. The duration
      of lay CPR before the first defibrillation either by the first or the second tier
      is known in 357 cases. This duration was more than 5 min and 10 min, in 80% and
      53% of the cases, respectively. The median (Q1, Q3) lay CPR duration was 11 (7,
      15) min. Survival to hospital discharge in this subgroup was achieved in 80/357
      (22%) patients. Using Weaver's linear model for survival after witnessed VF/VT,
      an estimated increase of more than 30% in survival rate was calculated.
      CONCLUSION: It is concluded that in our EMS system, laymen reach a substantial
      number of VF/VT victims many minutes before the arrival of the professional EMS
      teams. Therefore, a substantial increase in the number of survivors could be
      expected if lay responders were prepared to use an AED.

PMID- 9627066
TI  - Should a cancer patient be resuscitated following an in-hospital cardiac arrest?
AB  - OBJECTIVE: Previous reports from general hospitals and cancer centers have
      identified the presence of malignancy as a poor prognostic indicator for
      successful cardiopulmonary resuscitation (CPR) for an in-hospital cardiac arrest.
      The purpose of this study was to evaluate the initial success of CPR as
      determined by return of spontaneous circulation (ROSC), patient survival to
      hospital discharge, and 1-year survival of this group as compared to previous
      studies in non-oncological centers. In addition, the charges incurred in caring
      for these patients were analyzed. MATERIALS AND METHODS: All cardiac arrests
      occurring between 1 January 1993 and 31 December 1994 were identified from a
      centralized morbidity and mortality database and reviewed retrospectively.
      Cardiac arrest was defined as the absence of a palpable pulse and initiation of
      CPR. Patients suffering pure respiratory arrest or shock without loss of pulse
      were excluded. Age, gender, primary site of malignancy, initial and ultimate
      outcome, including Zubrod's functional status (ZFS), and total hospital charges
      following cardiac arrest were recorded. Computerized billing records were used to
      tabulate total charges. RESULTS: 83 cardiac arrests occurred during the study
      period (42 women, 41 men). Mean age was 56.2 years. Forty-two percent of the
      patients had hematologic malignancies, 19% lung, 15% gastrointestinal, 5% head
      and neck cancers and 19% other malignancies. Sixty-six percent of the patients
      had ROSC. Only eight (9.6%) patients survived to hospital discharge: three died
      within 6 weeks under hospice care, two died within 6 months of discharge and only
      three (3.6%) patients survived to 1 year. Functional status follow-up of these
      three patients revealed two with ZFS 1 and one with ZFS 2. Total hospital charges
      for these 83 patients were US$ 2,959,740. CONCLUSIONS: Although ROSC after
      cardiac arrest in our patients was better than that reported for most series in
      general hospitals, their ultimate survival and hospital discharge was extremely
      poor.

PMID- 9627067
TI  - The study of the effectiveness of chest compressions using the CPR-plus.
AB  - Effective cardiopulmonary resuscitation (CPR) requires a high level of skill from
      both healthcare professionals and the lay public. Inadequate chest compressions
      are a common cause of ineffective CPR. The CPR-plus is a non-invasive, hand-held,
      simple to use CPR adjunct designed to assist the rescuer to monitor and modify
      the compression technique during CPR, hopefully resulting in improved rescuer
      performance and more effective CPR. Forty qualified nurses were evaluated while
      they performed chest compressions on a training manikin. During simulated two
      rescuer CPR (compression/ventilation ratio 5:1) the participants performed 150
      compressions at a rate of 80-100 min. Compressions were performed with and
      without the CPR-plus and the results compared. The use of the CPR-plus was
      randomised with regard to whether the adjunct or the standard method was used
      first. The average number of correctly applied compressions was significantly
      better when the CPR-plus was used: 138.35/150 versus 110.70/150 (p = 0.0001).
      Improvements in techniques associated with the use of the CPR-plus also included
      a reduction in excessive application of pressure and incorrect hand position. The
      device provided reassurance of satisfactory compressions and an indication of
      impending fatigue in the rescuer.

PMID- 9627068
TI  - Effects of lidocaine and mexiletine on defibrillation energy requirements in
      animals treated with flecainide.
AB  - We previously reported that mexiletine alone did not increase the ventricular
      defibrillation threshold (DFT). However it has been stressed that the interaction
      of antiarrhythmic drugs may be one of the cause of sudden death in patients
      taking flecainide or encainide. In the present study, the effect of lidocaine and
      mexiletine combined with flecainide on DFT was investigated. Experiments were
      performed on 27 mongrel dogs. Flecainide 2 mg kg(-1) was administered i.v. as a
      loading dose and repeated for maintenance. Lidocaine (n = 10) or mexiletine (n =
      10), was cumulatively administered 15 min later. Saline was administered in
      control group (n = 7). In these groups, fibrillation/defibrillation trials were
      repeated. The flecainide concentration ranged from 0.84 to 1.02 microg ml(-1).
      The lidocaine and mexiletine concentrations increased up to 12.54 and 7.47 microg
      ml(-1), respectively. DFT15, 15 min after the administration of flecainide,
      increased from 2.0 to 3.2 J in lidocaine group (mean +/- S.E.M.; P < 0.05), from
      2.1 to 3.7 J in mexiletine group (mean +/- S.E.M.; P < 0.05). DFT increased with
      lidocaine concentrations of 3.42 microg ml(-1) or higher, and mexiletine of 3.60
      microg ml(-1) or higher (P < 0.05). In conclusion, both lidocaine and mexiletine
      elevated the DFT in the dog treated with flecainide, especially with lidocaine in
      a therapeutic concentration.

PMID- 9627069
TI  - Hemodynamic effects of repeated doses of epinephrine after prolonged cardiac
      arrest and CPR: preliminary observations in an animal model.
AB  - STUDY PURPOSE: To assess the hemodynamic response to repeated doses of
      epinephrine (EPI) in an animal model of prolonged cardiac arrest and CPR. DESIGN:
      Basic laboratory investigation. Fourteen canines were subjected to electrically
      induced ventricular fibrillation (VF) followed by 7.5 min of VF without CPR.
      INTERVENTIONS: After 7.5 min of VF, manual closed-chest CPR (80-100 compressions
      per minute, compression to ventilation ratio 8:1) was initiated. Countershocks
      were performed, recommended advanced cardiac life support drugs were given, and
      CPR was continued until restoration of spontaneous circulation (ROSC) or for 20
      min. Epinephrine, 1 mg (approximately 0.04 mg kg(-1)), was administered when
      indicated and at recommended time intervals. METHODS: Aortic and right atrial
      pressures were measured with micromanometer catheters before and after EPI, and
      CPR coronary perfusion pressure (CPP) was calculated (CPR diastolic aortic to
      right atrial pressure difference). Survival was defined as maintenance of ROSC
      for 30 min. RESULTS: Countershocks after 7.5 min resulted in asystole in ten
      animals and persistant VF in four. In those animals successfully resuscitated (n
      = 3), the change in CPP was 21 +/- 11 mm Hg after the first dose of EPI. Only one
      animal required a second dose of EPI. The majority of the study group (n = 11)
      could not be resuscitated. The increase in CPP after EPI averaged only 3 +/- 2 mm
      Hg and subsequent doses produced no significant effect on CPP (2 +/- 4 mm Hg).
      CONCLUSIONS: The hemodynamic response to the first dose of EPI determines if the
      critical CPP needed for ROSC and survival will occur. Repeat doses of EPI do not
      appear to improve CPP to a degree to affect clinically meaningful measures of
      outcome, i.e., successful countershock and survival.

PMID- 9627070
TI  - Plasma catecholamine levels following tracheal and intravenous epinephrine
      administration in swine.
AB  - We compared plasma epinephrine levels after three different tracheal epinephrine
      application techniques and intravenous injection in male and female anesthetized
      and paralyzed domestic pigs. Epinephrine was administered intravenously (10
      microg/kg) (group i.v.) or tracheally (100 microg/kg) either by direct injection
      into the upper end of the tracheal tube (group Tube), via a suction tube placed
      into the bronchial system (group Catheter) or using an EDGAR tube (group EDGAR),
      each group: n = 8. Arterial plasma samples were drawn before and 0.5, 1, 1.5, 2,
      2.5, 3, 4, 5, 6, 7 and 10 min after epinephrine administration. Plasma
      concentrations of epinephrine were measured with high pressure liquid
      chromatography using electrochemical detection. Analysis was performed by
      regression analysis for correlated data. Total plasma epinephrine concentrations
      showed a significant increase within 0.5 min in all groups. However, peak plasma
      epinephrine levels in group i.v. were significantly higher than in tracheal
      groups, while no differences between tracheal groups over the time were found. We
      conclude that in swine with spontaneous circulation tracheal instillation
      techniques using special devices such as suction tubes or EDGAR tubes result in
      onset and peak plasma epinephrine levels equivalent to those after direct
      injection into the upper end of the tracheal tube.

PMID- 9627071
TI  - Effect of DC shock on serum levels of total creatine kinase, MB-creatine kinase
      mass and troponin T.
AB  - After successful resuscitation from cardiac arrest, it is important to identify
      whether the event has been triggered by a myocardial infarction, since this
      determines subsequent investigations and management. Previous studies have shown
      that biochemical indices of infarction become elevated after resuscitation in
      patients without myocardial infarction. This can lead to overdiagnosis of
      myocardial infarction in the post-arrest setting. The cause of the elevated
      enzyme levels is not known, but may involve electrical or mechanical injury to
      the heart during resuscitation. In this study we aimed to identify the effects of
      isolated direct current shock on serum levels of creatine kinase (CK), MB
      creatine kinase mass (MB-CK), and troponin T, and examined the relationships
      between enzyme levels and the dose of electrical energy used. Thirteen patients
      were studied who underwent DC cardioversion for atrial fibrillation. Serum was
      obtained for CK, MB-CK and troponin T estimation before and 10 min after
      cardioversion, at hourly intervals for 8 h, and 18 h after cardioversion. Total
      serum CK became significantly elevated after only 3 h and rose to a peak of
      1294.4 IU l(-1) (P < 0.02) at 18 h. Post-shock CK levels were strongly correlated
      with total shock energy (r = 0.8, P < 0.01). Serum MB-CK was significantly
      elevated at 18 h among patients receiving total shock energies greater than 1000
      J than in those receiving lower doses, reflecting a positive correlation (r =
      0.64, P < 0.05) between shock energy and peak MB-CK level. Troponin T levels were
      not significantly elevated after cardioversion. In conclusion, total serum CK
      levels become significantly elevated early after cardioversion, suggesting rapid
      wash-out from injured skeletal muscle. MB-CK levels become significantly elevated
      in individuals receiving high energy shocks, probably due to release of small
      quantities of the CK-MB isoform from skeletal muscle. The negligible troponin T
      levels seen after high energy cardioversion indicate that significant myocardial
      injury does not occur. Electrical injury is not likely to account for the
      elevated troponin T levels seen after out-of-hospital resuscitation in patients
      without myocardial infarction.

PMID- 9627072
TI  - Logistic regression model to predict outcome after in-hospital cardiac arrest:
      validation, accuracy, sensitivity and specificity.
AB  - OBJECTIVE: To develop and validate a logistic regression model to identify
      predictors of death before hospital discharge after in-hospital cardiac arrest.
      DESIGN: Retrospective derivation and validation cohorts over two 1 year periods.
      Data from all in-hospital cardiac arrests in 1986-87 were used to derive a
      logistic regression model in which the estimated probability of death before
      hospital discharge was a function of patient and arrest descriptors, major
      underlying diagnosis, initial cardiac rhythm, and time of year. This model was
      validated in a separate data set from 1989-90 in the same hospital. Calculated
      for each case was 95% confidence limits (C.L.) about the estimated probability of
      death. In addition, accuracy, sensitivity, and specificity of estimated
      probability of death and lower 95% C.L. of the estimated probability of death in
      the derivation and validation data sets were calculated. SETTING: 560-bed
      university teaching hospital. PATIENTS: The derivation data set described 270
      cardiac arrests in 197 inpatients. The validation data set described 158 cardiac
      arrests in 120 inpatients. INTERVENTIONS: none. MEASUREMENTS AND RESULTS: Death
      before hospital discharge was the main outcome measure. Age, female gender,
      number of previous cardiac arrests, and electrical mechanical dissociation were
      significant variables associated with a higher probability of death. Underlying
      coronary artery disease or valvular heart disease, ventricular tachycardia, and
      cardiac arrest during the period July-September were significant variables
      associated with a lower probability of death. Optimal sensitivity and specificity
      in the validation set were achieved at a cut-off probability of 0.85.
      CONCLUSIONS: Performance of this logistic regression model depends on the cut-off
      probability chosen to discriminate between predicted survival and predicted death
      and on whether the estimated probability or the lower 95% C.L. of the estimated
      probability is used. This model may inform the development of clinical practice
      guidelines for patients who are at risk of or who experience in-hospital cardiac
      arrest.

PMID- 9627073
TI  - Quality of CPR during transport.

PMID- 9627074
TI  - Effects of hypokalaemia on arrhythmogenic risk of quinidine in rats.
AB  - Plasma potassium concentration plays an important role in the induction of
      arrhythmia and is closely related to the arrhythmogenicity of various drugs. We
      quantitatively analyzed the influence of plasma potassium concentration on QT
      intervals before drug administration and on drug-induced QT prolongation, to
      estimate the risk of drug-induced arrhythmia under hypokalaemic conditions. The
      hypokalaemic models were produced by intraperitoneal administration of furosemide
      and hydrochlorothiazide in male Sprague-Dawley rats. The relationship between the
      changes in QT intervals and time profiles of plasma quinidine (QND) concentration
      were analyzed during constant intravenous infusion of QND (10 or 30 mg/kg/h) and
      post infusion in normal and hypokalaemic rats. The plasma QND concentration
      reached the therapeutic range (3-7 microg/ml) at the high infusion rate (30
      mg/kg/h). No pharmacokinetic differences between normal and hypokalaemic rats
      were observed. QND induced QT prolongation in parallel with the plasma
      concentration without hysteresis. Although the potency of QND for QT prolongation
      was not affected by hypokalaemia, the QT intervals before drug administration
      were significantly prolonged in hypokalaemic rats (65.90 +/- 1.40 vs 56.60 +/-
      0.748 msec, mean +/- SEM, p < 0.0001). Thus, the prolongation of QT intervals
      before drug administration may act as a risk factor of arrhythmia under
      hypokalaemic conditions.

PMID- 9627075
TI  - Differential sensitivity to ATP-sensitive potassium channel openers of
      norepinephrine-induced contraction of guinea pig and rat aorta.
AB  - Vasorelaxant effects of ATP-sensitive potassium (K(ATP)) channel openers were
      examined on the tonic phase of vascular contraction induced by norepinephrine
      (NE) in guinea pig and rat aorta. K(ATP) channel openers, NIP-121 and cromakalim,
      produced glibenclamide-sensitive and concentration-dependent relaxations in
      guinea pig and rat aorta preconstricted with NE. However, the vascular
      relaxations induced by both K(ATP) channel openers were less pronounced in guinea
      pig aorta than in rat aorta. D-cis-Diltiazem, at the concentration up to 10(-5)
      M, did not appreciably inhibit the NE-induced contraction of guinea pig aorta,
      whereas the compound almost completely inhibited the NE-induced contraction of
      rat aorta at the same concentration. By contrast, sodium nitroprusside relaxed
      the NE-induced contractions in both guinea pig and rat aorta with similar
      potencies. These findings suggest that vasorelaxant effects of K(ATP) channel
      openers on the NE-induced sustained contraction in guinea pig aorta is not
      attributable to the subsequent inhibition of Ca2+ influx through L-type voltage
      gated Ca2+ channels. Lower sensitivity of guinea pig aortic smooth muscle to
      K(ATP) channel openers is most likely due to the low dependence of NE-induced
      contraction on the Ca2+ influx in this vascular smooth muscle.

PMID- 9627076
TI  - Neurotropin induces antinociceptive effect by enhancing descending pain
      inhibitory systems involving 5-HT3 and noradrenergic alpha2 receptors in spinal
      dorsal horn.
AB  - Neurotropin, a non-protein extract from the inflamed skin of rabbits inoculated
      with vaccinia virus, has been clinically used as an analgesic drug in Japan. Its
      analgesic effect has been demonstrated by reduced mechano-nociception in
      hyperalgesic rats exposed to SART-stress (a repeated cold stress) for 5 days. In
      order to clarify the mechanism of the analgesic effect of neurotropin at the
      spinal cord level, we examined the effects of several neurotransmitter receptor
      antagonists given by intrathecal (i.t.) injection on the antinociceptive effect
      of intraperitoneally (i.p.) injected neurotropin [100 and 200 Neurotropin Unit
      (NU)/kg]. The analgesic effect of neurotropin was significantly inhibited not
      only by methysergide (100 nmol/rat, i.t.), a non-selective antagonist against
      serotonin (5-HT), but also MDL 72222 (30 nmol/rat, i.t.), a selective 5-HT3
      antagonist, but not influenced by ketanserin (100 nmol/rat, i.t.), a 5-HT2A
      antagonist. The antinociceptive effect of neurotropin (200 NU/kg, i. p.) was
      significantly inhibited also by yohimbine (30 nmol/rat, i.t.), a noradrenergic
      alpha2 antagonist. However, the analgesic effect of neurotropin (100 and 200
      NU/kg, i.p.) was not influenced by naloxone (30 nmol/rat, i.t.), an opioid
      antagonist. These results suggest that the mechanism of the antinociceptive
      effect of neurotropin is via enhancement of endogenous descending pain inhibitory
      pathways of the serotonergic and noradrenergic systems, especially involving 5
      HT3 and noradrenergic alpha2 receptors in spinal dorsal horn in which these
      neurons terminate. No influence of opioid receptors at the spinal cord level is
      indicated.

PMID- 9627077
TI  - Effect of homocysteine and cholesterol in raising plasma homocysteine,
      cholesterol and triglyceride levels.
AB  - A high plasma homocysteine level is a newly regarded risk factor for coronary
      artery disease. We report a synergistic effect of homocysteine plus cholesterol
      feeding on further raising total plasma homocysteine, cholesterol and
      triglycerides levels than each agent alone, which further enhances the risk of
      coronary artery disease.

PMID- 9627078
TI  - Vascular endothelial growth factor upregulates constitutive cyclooxygenase 1 in
      primary bovine and human endothelial cells.
AB  - The effect of the angiogenic cytokine vascular endothelial growth factor (VEGF)
      on nitric oxide synthase (NOS) and cyclooxygenase (COX) expression was examined
      in human (HUVEC) and bovine (BAE) endothelial cells. VEGF (10 ng/ml) induced
      constitutive COX-1 expression in both HUVEC and BAE, but not the cytokine
      inducible isoform, COX-2, inducible NOS or endothelial NOS. In HUVEC, VEGF (10
      ng/ml) increased COX activity, but COX inhibitors had no effect on the
      proliferative response of endothelial cells to this cytokine. In conclusion the
      induction of COX-1 by VEGF is not involved in the mitogenic response of
      endothelial cells, but may be an important regulatory mechanism in the
      maintenance of vascular integrity.

PMID- 9627079
TI  - Inhibition of platelet serotonin uptake by cytochrome P450 inhibitors miconazole
      and econazole.
AB  - Serotonin uptake in human platelets was inhibited by cytochrome P450 inhibitors
      such as miconazole and econazole but not clotrimazole. There was a correlation
      between inhibition of serotonin uptake and inhibition of imipramine binding,
      suggesting that these P450 inhibitors may inhibit serotonin uptake via direct
      binding to the transporter. P450 inhibitor effects on serotonin uptake did not
      seem to be related to the effects of these compounds on intracellular calcium
      mobilization. Additionally, nitric oxide pathway stimulation does not appear to
      be involved.

PMID- 9627080
TI  - Low levels of eicosapentaenoic and docosahexaenoic acids mimic the effects of
      fish oil upon rat lymphocytes.
AB  - Fish oil is rich in the long chain n-3 polyunsaturated fatty acids
      eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA); typically these fatty
      acids constitute 20 to 25 g/100 g total fatty acids in fish oil. Feeding rodents
      diets rich in fish oil has been shown to decrease lymphocyte proliferation and
      natural killer cell activity. It is not known what level of EPA + DHA is required
      in the diet to exert these effects. This question was addressed in the current
      study. Weanling rats were fed on high fat (178 g/kg) diets which contained 4.4 g
      alpha-linolenic acid (control) or 4.4 g EPA + DHA (4.4 EPA + DHA) or 6.6 g EPA +
      DHA (6.6 EPA + DHA)/100 g total fatty acids. The n-6 to n-3 polyunsaturated fatty
      acid ratio was maintained at approximately 7. The fatty acid compositions of the
      serum and of spleen leukocytes were markedly influenced by that of the diet.
      Spleen lymphocyte proliferation in response to concanavalin A, spleen natural
      killer cell activity and PGE2 production by spleen leukocytes were reduced by
      feeding the EPA + DHA diets compared with feeding the control diet; the 4.4 and
      6.6 EPA + DHA diets caused very similar reductions. The 4.4 EPA + DHA diet
      reduced popliteal lymph node weight following a localised graft versus host
      response; this response was not investigated in rats fed the 6.6 EPA + DHA diet.
      The reductions in lymphocyte functions and in the in vivo graft versus host
      response caused by the EPA + DHA diets were similar to those previously reported
      following the feeding of diets rich in fish oil. Thus, this study shows that
      diets containing relatively low levels of EPA + DHA (20 to 25% of the level found
      in fish oil) exert immunomodulatory effects. Furthermore, this study suggests
      that the maximal effect of EPA + DHA is exerted when these fatty acids constitute
      a level of less than or equal to 4.4 g/100 g total dietary fatty acids.

PMID- 9627081
TI  - Enhanced hemodynamic response to [D-ALA2,D-MET5]-methionine enkephalin (DAME) in
      streptozotocin-induced diabetic rats is reversed by insulin replacement.
AB  - The present study examined the alterations of hemodynamic responses to [D-ala2,D
      Met5]-methionine enkephalin (DAME) in diabetic animals. Male Sprague-Dawley rats
      (12 weeks old) were used for this study. Diabetes was induced by a single
      injection of streptozotocin (65 mg/kg, i.v.). After 7 days, blood glucose levels
      were determined to confirm the diabetic state. Animals were anesthetized and
      instrumented to monitor mean arterial pressure, hindlimb bloodflow and hindlimb
      vascular resistance. Administration of DAME produced a significantly greater
      reduction in blood pressure, increase in hindlimb bloodflow and decrease in
      hindlimb vascular resistance in diabetic vs. control rats. These effects were
      blocked by naloxone. All hemodynamic changes were attenuated after pretreatment
      with the ganglionic blocker, hexamethonium, indicating that the responses were
      mediated either within the central nervous system or at the ganglia. Insulin
      reversed the exaggerated depressor effect of DAME on streptozotocin-treated rats.
      Collectively, these results suggest that diabetic rats have altered opioidergic
      hemodynamic responses to DAME due to mu receptor alterations in the CNS or in
      autonomic ganglia. These effects were reversed by replacement of insulin.

PMID- 9627082
TI  - Intralymphocyte free magnesium and plasma triglycerides.
AB  - To evaluate the relative effect of hypertension and plasma triglycerides on
      intralymphocyte magnesium we measured ionized intralymphocyte magnesium (Mg(i))
      concentration by means of a fluorimetric method based on the dye Furaptra in 4
      groups of subjects: 18 normotensive normotriglyceridemic controls (NTNC), 9
      hypertriglyceridemic normotensive patients (HTN), 8 hypertriglyceridemic
      essential hypertensive patients (HTEH), 17 normotriglyceridemic essential
      hypertensive patients (NTEH). Hypercholesterolemic, diabetic patients and
      alcoholics were excluded from the study. Mg(i) was found to be statistically
      reduced (ANOVA test F=10.41, P=0.0001) in both HTN and HTEH (M+/- SD, HTN: 0.235
      +/- 0.01, HTEH: 0.236 +/- 0.01 mmol/l) as compared to both NTNC and NTEH (M +/-
      SD, NTNC: 0.294 +/- 0.008, NTEH: 0.297 +/- 0.009 mmol/l). A statistically
      significant negative correlation was found in the population as a whole between
      Mg(i) and plasma triglycerides (n=52, R= -541, P=0.00004). Our data suggest that
      hypertriglyceridemia per se and possibly the so-called plurimetabolic syndrome is
      characterized by low intralymphocyte free magnesium.

PMID- 9627083
TI  - Down-regulation of interleukin-1beta production and PGE2 accumulation by an
      indomethacin-phenylalanine derivative in human monocytes.
AB  - This study was initiated to investigate the mechanism of action of a new
      indomethacin derivative, indomethacin-phenylalanine (indo-Phe) in human
      monocytes. We determined the effect of indo-Phe on the induction by LPS of
      prostaglandin-E2 (PGE2) and interleukin-1beta (IL-1beta) production in human
      monocytes. Indomethacin and indo-Phe inhibited the PGE2 synthesis in treated and
      untreated IL-1beta or LPS-treated monocytes. Furthermore, in IL-1beta and LPS
      treated monocytes, prostaglandin G/H synthase-1 (PGHS-1) protein expression was
      down-regulated with indomethacin or its indo-Phe analog whereas the level of the
      inducible protein (PGHS-2) was up-regulated. We analyzed the effect of
      indomethacin and indo-Phe on the expression of IL-1beta protein in LPS-treated
      monocytes and found that indo-Phe blocked the LPS-induction of IL-1beta synthesis
      while indomethacin did not. These differential effects of indomethacin and indo
      Phe suggest that two independent ways are involved in the stimulation of
      monocytes by LPS: the PGHS-2 protein induction and the IL-1beta secretion.

PMID- 9627084
TI  - Pontine cholinergic respiratory depression in neonatal and young rats.
AB  - We postulated that activation of pontine cholinergic mechanisms would cause
      respiratory depression in neonatal and young rats. Phrenic activity was recorded
      in decerebrate, paralyzed, ventilated and vagotomized rats of 4 to 22 days after
      birth. Small volumes (10-60 nl) of carbachol (44-88 mM) were injected into the
      medial portion of the rostral pons. The injection of carbachol, but not saline,
      decreased phrenic peak activity (83 +/- 6% of control) and respiratory frequency
      (64 +/- 9.5% of control) within 2 min following the injection in neonates and the
      depression lasted for less than 10 min. The site of injection in the pontine
      reticular formation was confirmed by histology. Results suggest that cholinergic
      mechanisms in the medial pons depress respiratory activity in the neonate.

PMID- 9627085
TI  - Cranberry extract inhibits low density lipoprotein oxidation.
AB  - Cranberry juice consumption is often used for the treatment of urinary tract
      infections, but the effect of cranberry juice on heart disease has not been
      investigated. We evaluated how a cranberry extract containing 1,548 mg gallic
      acid equivalents/liter (initial pH=2.50) affected low density lipoprotein (LDL)
      oxidation induced by 10 micromolar cupric sulfate. When LDL oxidation took place
      in the presence of diluted cranberry extracts, the formation of thiobarbituric
      acid reactive substances (TBARS) and LDL electrophoretic mobility were reduced.
      LDL electrophoretic migration was also reduced when the cranberry extract had a
      pH of 7.00 prior to dilution. This study suggests that cranberry extracts have
      the ability to inhibit the oxidative modification of LDL particles.

PMID- 9627086
TI  - Effects of methylenechloride-soluble fraction of Japanese angelica root extract,
      ligustilide and butylidenephthalide, on pentobarbital sleep in group-housed and
      socially isolated mice.
AB  - We previously showed that the extract of Japanese angelica root (JAR-E) reversed
      the decrease in pentobarbital (PB) sleep induced by isolation stress and
      yohimbine and methoxamine, stimulants of central noradrenergic systems, in mice.
      Here, we tested the effects of several fractions from JAR-E and ligustilide and
      butylidenephthalide, phthalide components of JAR-E, on PB sleep in isolated mice
      to elucidate the mechanism of the action of JAR-E. Methanol-soluble (Met-S) and 
      insoluble (Met-IS) fractions were obtained from JAR-E. Methylenechloride-soluble
      (MC-S) and -insoluble fractions (MC-IS) were prepared from Met-S. MC-S (11.4-76
      mg/kg, p.o.) reversed the isolation stress-induced decrease in PB sleep, but
      neither Met-IS (0.8-2.4 g/kg, p.o.) nor MC-IS (0.7-2 g/kg, p.o.) had the same
      effect. The i.p. administration of MC-S exhibited a similar activity to that
      observed after the p.o. administration of the same fraction. Ligustilide (5-20
      mg/kg, i.p.) and butylidenephthalide (10-30 mg/kg, i.p.) reversed PB sleep
      decrease in isolated mice. Both components (20 mg/kg, i.p.) attenuated the
      suppressive effects of yohimbine (30 nmol, i.c.v.), methoxamine (200 nmol,
      i.c.v.) and a benzodiazepine inverse agonist FG7142 (10 mg/kg, i.p.) on PB sleep
      in group-housed mice. These results suggest the contribution of ligustilide and
      butylidenephthalide to the effect of JAR-E on PB sleep in isolated mice, and
      implicate central noradrenergic and/or GABA(A) systems in the effects of these
      components.

PMID- 9627087
TI  - Tyrosine hydroxylase gene expression in the locus coeruleus of depression-model
      rats and rats exposed to short-and long-term forced walking stress.
AB  - Abnormal brain noradrenergic function is thought to cause depressive illnesses
      which are sometimes manifested or aggravated under stressful conditions. To
      investigate the effect of chronic stress on noradrenaline (NA) synthesis in the
      brain we used in situ hybridization to examine the expression of tyrosine
      hydroxylase (TH) mRNA in the locus coeruleus (LC) of "depression-model rats" that
      exhibit reduced activity following exposure to long-term (14 days) forced walking
      stress (FWS). We also examined TH mRNA expression in rats stressed for 30
      minutes, 3 hours and 1, 2 (short-term), 6 or 12 (long-term) days. The expression
      of TH mRNA increased markedly following 1 to 12 days of FWS, but not in rats
      exposed to FWS for 30 minutes or 3 hours. The expression also increased
      significantly in the depression-model rats, but not in the "spontaneous recovery
      rats" whose activity was restored after long-term stress. Our results suggest
      that NA synthesis remains high in the FWS-induced depression-model rats because
      of the high levels of TH mRNA expression in the LC. Our results also suggest that
      FWS is initially a mild stress but gradually becomes a severe form of unadaptable
      stress as reflected by delayed but persistent increases in TH mRNA expression.

PMID- 9627088
TI  - Characterization of nitric oxide synthase activity in rabbit uterus and vagina:
      downregulation by estrogen.
AB  - Nitric oxide synthase (NOS) was determined in the soluble (cytosolic) and
      particulate fractions of rabbit uterus, vagina and cerebellum and the influence
      of estrogen treatment on NOS activity was studied. NOS in both the cytosolic and
      particulate fractions was highly calcium dependent. The activity in cytosolic
      fraction was nearly 4-fold higher than the particulate fractions from all three
      organs. The concentration of NOS was highest in cerebellum followed by vagina and
      uterus. Vaginal NOS activity was 3-4-fold higher than the uterine NOS. After a
      continuous treatment of rabbits for one week with estrogen, cytosolic NOS was
      reduced by nearly 7 and 4-fold in the uterus and vagina, respectively, whereas
      there was no significant change in the particulate NOS. Estrogen treatment caused
      no change in cytosolic or particulate NOS from the cerebellum. Downregulation of
      cytosolic NOS by estrogen in the estrogen target tissues like uterus and vagina
      and absence of effect in the cerebellum strongly suggests a physiological
      significance.

PMID- 9627089
TI  - Effects of carbon monoxide exposure on serotonergic neuronal systems in rat
      brain.
AB  - It is well known that some psychiatric sequelae exist after CO poisoning, but few
      animal studies on serotonergic neuronal function after CO exposure have been
      carried out. We investigated the effects of successive carbon monoxide (CO)
      exposure (6000 ppm, 10 min, 3 repetitions) on serotonergic neuronal systems in
      rat brain. Serotonin (5-HT) concentrations were significantly decreased only in
      the frontal cortex from 1 hr to 7 days after CO exposure. 5-Hydroxyindoleacetic
      acid (5-HIAA) concentrations were significantly increased at 1 hr in all six
      brain regions measured (frontal cortex, striatum, hypothalamus, hippocampus,
      midbrain, and pons). 5-HT synthesis, measured by the accumulation of 5
      hydroxytryptophan (5-HTP) after the administration of m-hydroxybenzylhydrazine
      (NSD-1015), was significantly decreased in all regions from 1 hr to 7 days after
      CO exposure. [3H]Ketanserin (5-HT2A) binding sites in the frontal cortex were not
      affected by CO exposure. DOI-induced head shakes, a 5-HT2A receptor mediated
      behavior, were not changed after CO exposure. These findings indicated that CO
      exposure caused presynaptic serotonergic neuronal dysfunctions that consisted
      mainly of decreased concentration of 5-HT in the frontal cortex or a decrease of
      5-HT synthesis in all six regions, without compensatory hyperfunction of 5-HT2A
      receptors.

PMID- 9627090
TI  - Biosynthesis of digitalis-like compounds in rat adrenal cells: hydroxycholesterol
      as possible precursor.
AB  - The biosynthesis of digitalis-like compounds (DLC) was determined in bovine and
      rat adrenal homogenates, as well as in primary rat adrenal cells, by following
      changes in the concentration of DLC using three independent sensitive bioassays:
      inhibition of [3H]-ouabain binding to red blood cells and competitive ouabain and
      bufalin ELISA. The amounts of DLC in bovine and rat adrenal homogenates, as
      measured by the two first bioassays, increased with time when the mixtures were
      incubated under tissue culture conditions. Rat primary adrenal cells were
      incubated in the presence of [1,2-(3)H]-25-hydroxycholesterol, [26,27-(3)H]-25
      hydroxycholesterol or [7-(3)H]-pregnenolone. The radioactive products, as well as
      the digitalis-like activity, were fractionated by three sequential chromatography
      systems. When [1,2-(3)H]-25-hydroxycholesterol or [7-(3)H]-pregnenolone was added
      to the culture medium, the radioactivity was co-eluted with digitalis-like
      activity, suggesting that at least one of the DLC might originate in
      hydroxycholesterol. In contrast, when the culture medium was supplemented with
      [26,27-(3)H]-25-hydroxycholesterol, the radioactivity was not co-eluted with the
      digitalis-like activity, indicating that side chain cleavage is the first step in
      the synthesis of digitalis-like compounds by rat adrenal.

PMID- 9627091
TI  - Behavioral deficits in monosodium glutamate rats: specific changes in the
      structure of feeding behavior.
AB  - We studied the feeding rhythms and feeding patterns of adult Long-Evans rats
      treated with monosodium glutamate (MSG) in their early post-natal period. This
      treatment is known to induce neuronal degeneration in the arcuate nucleus (ARC),
      a major hypothalamic site implicated in the regulation of feeding. Neonatal rats
      were treated intraperitoneally with MSG or saline (controls) alone on the first
      days of life. At age of 6 months, male control and male MSG rats were placed in
      our automatic feeding system, and the structure of feeding behavior and diurnal
      feeding rhythms were analysed. On a 24 hours basis, MSG rats ate less than
      control rats (-24%). This hypophagia resulted from a mild diurnal hyperphagia
      (+6%) and a pronounced nocturnal hypophagia (-34%). This hypophagia was the main
      consequence of a decrease of meal size in MSG rats (-37%) and was associated with
      an increase in meal duration (+52%). It was also associated with a total
      disappearance of the two feeding peaks that normally occur at light and dark
      onset in the rat (-90% 2 h after dark onset and -49% 2 h before light onset).
      These results indicate that neonatal treatment with MSG induces important changes
      in feeding patterns and feeding rhythms in the adulthood. These changes might be
      related to the disappearance of neurotransmitters located in the arcuate nucleus.

PMID- 9627092
TI  - Cyclic AMP decreases the availability of 5-phosphoribosyl-1-pyrophosphate and
      decelerates de novo purine synthesis in rat hepatocytes.
AB  - Cyclic adenosine monophosphate (cAMP) was found to decrease the availability of 5
      phosphoribosyl-1-pyrophosphate (PRPP) and to decelerate the rate of de novo
      purine synthesis in suspensions of adult rat hepatocytes. Glucagon did not affect
      these parameters. The glucagon antagonist des-His1[Glu9]glucagon amide (DHGA),
      and the protein kinase C activator 1,2-dioctanoyl-sn-glycerol (DOG) were also
      found to lower PRPP availability. Incubation of the hepatocytes with dbcAMP or
      with DHGA, did not alter the activity of PRPP synthetase in the hepatocyte
      lysates, indicating that the above effects are not mediated through the activity
      of this enzyme. The possibility that the decrease in PRPP availability reflects
      increased consumption associated with accelerated pyrimidine synthesis is
      discussed. The decelerated rate of de novo purine synthesis is probably secondary
      to the decreased PRPP availability.

PMID- 9627093
TI  - Circulating advanced glycation peptides in streptozotocin-induced diabetic rats:
      evidence for preferential modification of IgG light chains.
AB  - As the glycation/glycoxidation hypothesis for the genesis of diabetic
      complications is achieving widespread acceptance, much attention is being paid to
      the role of low molecular weight advanced glycation (AGE) adducts, as second
      generation glycating agents. We set out a study with the objective of attesting
      the presence of increased amounts of AGE-peptides in the circulation of
      streptozotocin-induced diabetic rats and to determine the nature of the plasma
      proteins which are main targets for advanced glycation. AGE (Ex 370/Em 440 nm)
      and pentosidine fluorescence (Ex 335/Em 385 nm) were significantly higher in
      plasma from diabetic rats after only one month of hyperglycemia as compared to
      controls (35 +/- 7 vs 25 +/- 2 AU, p< 0.05 and 54 +/- 14 vs 27 +/- 3 AU, p< 0.01
      respectively). AGE-peptides (<10 kDa) were more than two-fold higher in diabetic
      animals. Immunoblots after SDS-PAGE of plasma proteins showed that AGE-IgG
      displayed a selective predominant increment in the same animals. When native rat
      IgG was incubated in the presence of AGE-peptides isolated from diabetic animals,
      AGE modification was already apparent after only 24 h of incubation, and was
      particularly important for light chains. AGE-immunoreactive light chains
      displayed an apparent increase in molecular weight. Aminoguanidine prevented,
      while copper enhanced AGE binding to IgG light chains. Our data validate the
      streptozotocin-induced diabetic rat as a model reproducing the presence of
      circulating AGE-peptides, give evidence that IgG are preferential targets for
      advanced glycation in plasma and suggest that this modification, mediated by AGE
      peptides, can be prevented by aminoguanidine.

PMID- 9627094
TI  - Effect of melatonin on chloride secretion by human colonic T84 cells.
AB  - The effect of melatonin on human colonic T84 cells was studied using the short
      circuit current (I(SC)) technique. Basolateral, as well as apical, addition of
      melatonin stimulated I(SC) in a concentration-dependent manner (EC50 at about 100
      microM). The I(SC) response to melatonin was nearly abolished when external Cl-
      was removed. The increase in I(SC) was also blocked by apical addition of two Cl-
      channel blockers, 4,4'-diisothiocyanatostibene-2,2'-disulfonic acid (DIDS) and
      diphenylamine-2-carboxylic acid (DPC), indicating that melatonin stimulated Cl-
      secretion. The effect of different melatonin analogs was compared and the order
      of potency appeared to be 2-iodomelatonin > melatonin > 6-hydroxymelatonin,
      indicating the involvement of melatonin receptors. However, inhibitors for Gi
      protein, adenylate cyclase or phospholipase C were found to be ineffective in
      inhibiting the melatonin-induced I(SC). Pretreatment of the cells with melatonin
      was also found to exert little effect on subsequent forskolin- or VIP-induced
      I(SC), further excluding its interaction with adenylate cyclase. Our data suggest
      that melatonin may play a role in regulating colonic Cl- secretion via melatonin
      receptors; however, the signal transduction pathway(s) involved remains to be
      elucidated.

PMID- 9627095
TI  - Cyclooxygenase-independent chemoprevention with an aspirin derivative in a rat
      model of colonic adenocarcinoma.
AB  - Aspirin decreases the risk of colorectal cancer, reportedly through suppression
      of cyclooxygenase (COX) activity. Using a rat model of colonic adenocarcinoma, we
      compared the chemopreventative effects of aspirin versus a nitric oxide-releasing
      derivative (NCX-4016) which does not inhibit COX. Beginning six weeks after
      intracolonic administration of trinitrobenzene sulfonic acid, the rats were given
      azoxymethane weekly (15 mg/kg i.p.) for 4 weeks. Over the same 4-week period, the
      rats were treated daily with vehicle, aspirin (10 mg/kg) or NCX-4016 (equimolar
      dose). Six weeks later, the number of aberrant crypt foci (an early preneoplastic
      lesion) were blindly counted by light microscopy. Effects of aspirin vs. NCX-4016
      on COX-1 and COX-2 activity were compared, as was their analgesic activity. Rats
      receiving vehicle developed a mean of 856 +/- 260 aberrant crypt foci in the
      colon. Aspirin reduced the number of aberrant crypt foci by 64%, while NCX-4016
      produced an 85% reduction. Aspirin, but not NCX-4016, markedly suppressed
      systemic COX-1 and COX-2 activity, and colonic prostaglandin synthesis. Despite
      not inhibiting COX, NCX-4016 exhibited comparable analgesic activity to aspirin.
      These results demonstrate that NCX-4016, a nitric oxide-releasing aspirin
      derivative, exhibited superior chemopreventative effects to aspirin in this model
      of colon cancer. This effect occurred independent of inhibition of COX-1 or COX
      2.

PMID- 9627096
TI  - Distinct functional characteristics of levocabastine sensitive rat neurotensin
      NT2 receptor expressed in Chinese hamster ovary cells.
AB  - Neurotensin has been shown to produce pharmacological effects both in brain and
      periphery. Several of these effects are mediated by a high-affinity neurotensin
      NT1 receptor. On the other hand, a low-affinity levocabastine-sensitive
      neurotensin NT2 receptor was molecularly cloned from rodent brain recently. In
      this study, in contrast to NT1 receptor, levocabastine (a histamine H1 receptor
      antagonist) and SR48692 (an antagonist for NT1 receptor) strongly stimulated
      intracellular Ca2+ mobilization in transfected Chinese hamster ovary cells
      expressing rat NT2 receptor, thus acting as potent NT2 receptor. Furthermore,
      despite of their affinities for NT2 receptor, the Ca2+ responses to potent NT1
      agonists, neurotensin or JMV449 ([Lys8-(CH2NH)-Lys9]Pro-Tyr-Ile-Leu, a peptidase
      resistant analogue of neurotensin) were much smaller than that observed with
      SR48692. These findings suggest that NT1 and NT2 receptors present distinct
      functional characteristics and that SR48692 may act as a potent agonist for NT2
      receptor.

PMID- 9627097
TI  - Vasopressin and the regulation of hypothalamic-pituitary-adrenal axis function:
      implications for the pathophysiology of depression.
AB  - The role of arginine vasopressin (AVPNP) in the control of adrenocorticotropic
      hormone (ACTH) secretion is explored, and in particular, its involvement in
      various stress response paradigms which may be of relevance in our understanding
      of the pathophysiology of depression. VP is released from two sites in the
      hypothalamus; the parvicellular division of the paraventricular nucleus (PVN),
      where corticotropin releasing hormone (CRH) is also formed, and from the
      magnocellular neurons of the supraoptic nucleus (SON) and the PVN. The intricate
      interaction with CRH, the other main ACTH secretagogue, and with glucocorticoids,
      the inhibitory feedback component of hypothalamic-pituitary-adrenal-axis (HPA)
      activity, is outlined. That VP plays an important role in the stress response is
      now beyond doubt. Examination of the impact of psychological stressors on the
      differential expression of VP and CRH at a hypothalamic and pituitary level has
      been facilitated by advances in molecular biological techniques. Of importance
      has been the cloning of the V1b receptor gene, the receptor at which AVP is
      active in the anterior pituitary. Chronic stress paradigms, associated with HPA
      hyperresponsiveness, and ACTH release following a novel superimposed stress, have
      been found with relative consistency to show a shift in the CRH:AVP ratio. This
      may relate to differing feedback sensitivity of AVP to glucocorticoid feedback
      restraint and the greater responsivity of AVP over CRH to chronic stimulatory
      stress input. Evidence for functionally distinct pools of ACTH releasing
      corticotropes, and the finding that AVP levels more closely correlate with ACTH
      levels than do CRH levels, suggest a more dynamic role for AVP in activity of the
      stress axis, and a primarily permissive function for CRH. The renewed interest in
      the role of VP in HPA axis activity may have important implications for
      furthering our understanding of psychiatric conditions such as depression, where
      significant dysregulation of this axis is seen. Elevated baseline cortisol,
      dexamethasone non-suppression and blunted CRH/ACTH release have been consistently
      documented. The possible contribution of VP to this hyperactivity, despite its
      known synergy with CRH, has been largely neglected. In animal models there is
      clear evidence that chronic psychological stressors increase the ratio of AVP to
      CRH production. Psychosocial stressors are intrinsically linked with depressive
      illness. The finding of elevated levels of AVP in postmortem studies of
      depressives and the lowering of CSF AVP levels by antidepressants, raises the
      question of the precise role of AVP in the overactivity of the HPA in depression,
      a finding that is currently attributed to overdrive of its HPA regulatory
      companion, CRH.

PMID- 9627098
TI  - Glucose stimulates renin secretion via adrenergic mechanisms in the rat.
AB  - To elucidate whether and why glucose directly influences renin secretion, the
      effect of glucose on renin secretion was investigated in the rat. In an in vivo
      study, renin activity significantly (p<0.01) increased from the basal value of
      7.6 +/- 1.4 to 14.2 +/- 3.2 ng Ang I/ml/hr (mean +/- SD) after intravenous
      glucose (1.0 g/kg, in 50% glucose solution ) injection. Propranolol (10.5 mg/kg)
      pretreatment partly abolished the increase in renin activity induced by glucose
      injection. In an in vitro study, the isolated kidneys of male Wistar rats (200
      250 g) were perfused with a basal perfusing medium containing 5.5 mM glucose for
      20 min, and then perfused with the medium containing 16.5 mM glucose, 27.5 mM
      glucose, 5.5 mM glucose + 22 mM mannitol, 27.5 mM glucose + 1 microM
      phentolamine, or 27.5 mM glucose + 1 microM propranolol for 10 min, respectively.
      Renin activity was significantly increased from a basal value of 8.1 +/- 4.5 to
      peak value of 17.9 +/- 3.0 ng Ang I/ml/hr (p<0.01) by 16.5 mM glucose, to 59.0 +/
      10.5 ng Ang I/ml/hr (p<0.005) by 27.5 mM glucose, and to 24.7 +/- 5.8 ng Ang
      I/ml/hr (p<0.01) by 5.5 mM glucose + 22 mM mannitol. The increase in renin
      activity in the kidney perfused with 27.5 mM glucose was significantly (p<0.005)
      higher than that with 16.5 mM glucose or that with 5.5 mM glucose + 22 mM
      mannitol. The 27.5 mM glucose-stimulated increase in renin activity was not
      changed by the addition of 1 microM phentolamine, while it was completely
      abolished by the addition of 1 microM propranolol. These results suggest that
      glucose has a direct stimulating effect on renin secretion probably through beta
      adrenergic mechanisms in the rat.

PMID- 9627099
TI  - The effect of LHRH and TRH on human interferon-gamma production in vivo and in
      vitro.
AB  - Accumulating evidence suggests that hypothalamic luteinizing hormone-releasing
      hormone (LHRH) and thyrotropin-releasing hormone (TRH) are two hypophysiotropic
      factors which modulate the immune response. The aim of the present study was to
      determine the in vivo effects of an intravenous bolus of LHRH and TRH on plasma
      interferon (IFN)-gamma production in five normoprolactinemic women with irregular
      menstrual cycles. We also determined prolactin (PRL), thyrotropin (TSH), follicle
      stimulating hormone (FSH), and luteinizing hormone (LH) levels before and after
      intravenous administration of LHRH and TRH. The results demonstrate that
      intravenous bolus of LHRH/TRH increases plasma IFN-gamma levels, with the maximum
      response 45 min after in vivo administration of hypothalamic peptides and after
      peak levels of adenohypophyseal hormones (PRL: 15 min; TSH: 30 min; FSH: 30 min;
      LH: 30 min). In order to investigate a possible direct action of hypothalamic
      hormones on immune cells, we also evaluated, in the same subjects, the influence
      of LHRH and TRH on IFN-gamma production by human peripheral blood mononuclear
      cells (PBMCs), collected before the intravenous administration of the peptides
      and stimulated in vitro with bacterial superantigen staphylococcal enterotoxin A
      (SEA) and concanavalin A (Con A). LHRH and TRH, separately and together,
      significantly enhanced in vitro IFN-gamma production by SEA- and ConA-activated
      PBMCs. The present results suggest that hypothalamic peptides (LHRH and TRH)
      directly, and/or indirectly pituitary hormones (PRL, TSH, FSH, and LH) or IL-2,
      have stimulatory effect on IFN-gamma producing cells and are further evidence of
      interactions between the neuroendocrine and immune systems.

PMID- 9627100
TI  - Expression of the messenger RNA for gonadotropin-releasing hormone and its
      receptor in human cancer cell lines.
AB  - The presence of gonadotropin-releasing hormone (GnRH) binding sites in biopsy
      samples of human epithelial ovarian cancer and ovarian tumor cell lines as well
      as the demonstration of the inhibitory effects of GnRH analogues on the growth of
      these cells raised the possibility that GnRH is produced locally by ovarian
      cancer cells. In order to investigate an autocrine/paracrine regulatory mechanism
      in human carcinomas, we have studied the expression of GnRH and GnRHR mRNA in
      human ovarian epithelial cell lines (OVCAR-3 and SKOV-3), human choriocarcinoma
      cell line (JEG-3) and human hepatocarcinoma cell line (HepG 2). Using primers
      corresponding to published human GnRH and GnRHR cDNA sequences, predicted PCR
      products were obtained from these cell lines by reverse transcription-polymerase
      chain reaction (RT-PCR) and confirmed by Southern hybridization. Sequencing
      analysis of GnRH PCR products showed that their sequences have 100% identity to
      the published human GnRH cDNA sequence. These results indicated that GnRH and
      GnRHR genes are expressed in all the cell lines tested in the present study, and
      strengthen the concept that GnRH may act as an autocrine regulator on the growth
      of cancer cells.

PMID- 9627101
TI  - Differential regulation of hepatic arterial and portal venous vascular resistance
      by nitric oxide and carbon monoxide in rats.
AB  - Nitric oxide (NO), a gaseous mediator that accounts for the biological activity
      of endothelium-derived relaxing factor, has been shown to play an important role
      in the reduction of basal vascular tone in multiple vascular beds, including the
      hepatic circulation. On the other hand, recent studies have provided first
      evidence that endogenously generated carbon monoxide (CO) may exert vasodilatory
      effects in the hepatic portal vein and within sinusoids. Thus, we defined the
      differential role of NO and CO in the regulation of vascular resistance in the
      two inflows to the liver in the normal rat in vivo. Male Sprague-Dawley rats were
      anesthetized with pentobarbital sodium and surgically instrumented in order to
      study the change in hepatic arterial (Rha) and portal venous vascular resistance
      (Rpv) in response to intravenous bolus administration of either the NO-synthase
      inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) (1 mg/kg; n = 7
      animals) or of tin protoporphyrin-IX (SnPP-IX) (50 micromol/kg), a specific
      inhibitor of the CO-generating enzyme heme oxygenase (n = 8 animals). While L
      NAME caused a substantial increase in Rha, Rpv increased only slightly under
      these conditions. In sharp contrast, SnPP-IX did not affect Rha, but caused a
      profound increase in Rpv. In conclusion, Rha and Rpv are differentially regulated
      by NO and CO in the normal rat liver in vivo, i.e., NO serves as a potent
      vasodilator in the hepatic arterial circulation, but exerts only a minor
      vasodilatory effect in the portal venous vascular bed. In contrast, while there
      is no intrinsic CO-mediated vasodilation in the hepatic artery, CO acts to
      maintain portal venous vascular tone in a relaxed state.

PMID- 9627102
TI  - Effect of testosterone propionate treatment on thyrotropin secretion of young and
      old rats in vitro.
AB  - The aim of this study was to evaluate the influence of androgens on TSH secretion
      during aging in Dutch rats. Male young (2 months) and old (16-21 months) rats
      were castrated (Cx) or sham-operated (C) and received testosterone propionate (TP
      -4 mg/Kg B.W., i.m., 7 days) or vehicle. Female adult (3 months) and old (12 and
      17 months) intact rats received TP or corn oil in the same dose. The rats were
      decapitated, trunk blood was collected and anterior pituitaries were dissected
      out for in vitro incubation. In Cx young male rats, only TSH pituitary content
      showed lower levels than in their controls. Cx TP-treated rats showed higher
      serum TSH and in vitro basal and TRH-induced TSH secretion, but TP only partially
      reversed the decrease in pituitary TSH promoted by castration. The old male rats
      showed lower basal in vitro TSH secretion and pituitary TSH content. In Cx old
      male rats, serum and basal in vitro TSH concentrations were higher than those of
      old controls and TP treatment further increased basal in vitro TSH secretion, as
      well as, stimulated TRH-induced TSH secretion. Interestingly, TP had no effect on
      intact young or old male rats. However, in intact old female rats, TP stimulated
      in vitro TSH secretion but, as observed in the intact male, TP had no effect on
      adult female rats. These results suggest a stimulatory role of testosterone on
      TSH secretion of young and old male rats. Thereafter, it seems that the testes of
      old rats secrete some testicular factor that inhibits TSH secretion. However, in
      male rats with normal testosterone levels TP treatment did not increase further
      TSH secretion, but in old female rats it had a stimulatory effect.

PMID- 9627103
TI  - Stimulated prostaglandin E2 release from rat skin, in vitro.
AB  - The excitatory effect of bradykinin (BK) and of low pH on nociceptors appears to
      partly depend on secondary release of prostaglandins from the surrounding tissue.
      Rat skin, in vitro, is introduced as a novel model to measure basal and
      stimulated release of PGE2 and, in future, other substances relevant to
      nociception, such as neuropeptides. Flaps of hairy skin (n=57) from the rat
      saphenous region of the hindpaw were subcutaneously excised and fixed on acrylic
      rods, the corium side exposed. The preparations were equilibrated in carbogen
      gassed "synthetic interstitial fluid" (SIF) for 30 minutes. The skin flaps were
      then immersed for 5 minutes each in 9 consecutive glass tubes, which were mounted
      in a shaking bath at 32 degrees C. Each tube was filled with 5 ml of gassed SIF,
      the third tube contained inflammatory mediator(s) dissolved in SIF or solutions
      of low pH. After passage of the skin flap, the eluates were deep frozen (-70
      degrees C) and the PGE2 content measured, off-line, using an enzyme immuno-assay.
      As stimulants, BK at 10(-5) M (n=9) and 10(-6) M (n=4) and BK in equimolar
      combination with histamine (HA) and serotonin (5-HT; 10(-5) M: n=8, 10(-6) M:
      n=6, 10(-7) M: n=6) dose-dependently increased PGE2 release. Considering the
      total amount of PGE2 secreted the combination of inflammatory mediators caused a
      significantly greater release of PGE2 at 10(-5) and 10(-6) M (p<0.01, Kruskal
      Wallis test) than BK stimulation alone. Racemic flurbiprofen caused a profound
      depression of basal and stimulated release. Solutions of high proton
      concentration are known to stimulate and sensitize nociceptors. However,
      phosphate buffered SIF at pH 6.1 and 6.4 caused a substantial and significant
      decrease of the PGE2 release, probably due to low-pH block of phospholipases.
      Thus, algogenic potency of mediators does not necessarily match their pro
      inflammatory action.

PMID- 9627104
TI  - Chronopharmacological study of KE-SI-TO components in mice.
AB  - Influence of dosing time on pharmacological effects and toxicity of KE-SI-TO
      (KST) components, as well as the role of each component in the circadian rhythms
      of KST, was investigated in ICR male mice under an LD (12:12) cycle. The mice
      given Cinnamomi Cortex (258 mg/kg, i.p.) or Paeoniae Radix (258 mg/kg, i.p.)
      showed a significant circadian rhythm in the time spent on the hot plate with the
      shortest latency at 0900 and the longest one at 0100 (p<0.01, respectively). The
      mice given Cinnamomi Cortex or Glycyrrhizae Radix (129 mg/kg, i.p.) showed a
      significant circadian rhythm with the lowest rectal temperature (RT) at 1700 and
      the highest one at 0500 (p<0.01, respectively). Cinnamomi Cortex (850 mg/kg,
      i.p.)- or Glycyrrhizae Radix (2500 mg/kg, i.p.)-induced toxicity showed a
      significant circadian rhythm with the highest mortality at 1700 and the lowest
      one at 0500 (p<0.05, respectively). The rhythmic patterns of the drug-induced
      analgesia, hypothermia and toxicity resembled the overall rhythms occurring after
      KST (1000 or 6000 mg/kg, i.p.) injection. These results suggest that the
      circadian rhythms in actions of Cinnamomi Cortex, Paeoniae Radix and Glycyrrhizae
      Radix are mainly responsible for the rhythm in the effects and toxicity of KST.

PMID- 9627105
TI  - Monosodium glutamate lesions inhibit the N-methyl-D-aspartate-induced growth
      hormone but not prolactin release in rats.
AB  - Large doses of glutamate administered to newborn rats damage permanently the
      neurones in the hypothalamic arcuate nucleus containing the growth hormone
      releasing hormone and the prolactin inhibiting dopamine neuron cell bodies. Since
      adult animals that underwent neonatal glutamate treatment still have a relatively
      well functioning growth hormone and prolactin system, we tested whether in the
      adults the excitatory amino acid sensibility is changed. After i.v. injection of
      different doses (10 or 30 mg/kg) of N-methyl-D-aspartate (excitatory amino acid
      receptor subtype agonist) growth hormone levels were significantly increased in
      the control groups but there was no rise in neonatally glutamate treated male and
      female rats. The level of prolactin was increased by N-methyl-D-aspartate, too,
      but the glutamate treatment had no effect on the rise. Our study suggests that
      systemic administration of N-methyl-D-aspartate increases plasma growth hormone
      level by activating the growth hormone releasing cells in the arcuate nucleus,
      but the intact tuberoinfundibular dopaminergic pathway is not essential for its
      prolactin stimulatory effect.

PMID- 9627106
TI  - Inhibition of nitric oxide synthase results in a suppression of interleukin-1beta
      induced fever in rats.
AB  - Pro-inflammatory cytokines such as interleukin-1beta (IL-1beta) induce nitric
      oxide synthase. The purpose of this study was to investigate the role of
      endogenous nitric oxide in IL-1beta-induced fever in rats. At a dose of 2.5
      microg per animal intraperitoneal (i.p.) injections of rat recombinant IL-1beta
      evoked a febrile response with a duration of 8 hours. Simultaneous i.p. injection
      of 50 mg/kg N-nitro-L-arginine methyl ester hydrochloride (L-NAME) resulted in a
      complete suppression of IL-1beta-induced fever in rats. I.p. injection of 50
      mg/kg L-NAME alone had no apparent influence on body core temperature. Endogenous
      formation of IL-6 in response to IL-1beta was not suppressed but rather enhanced
      by treatment with L-NAME during the early stage of IL-1beta-induced fever. This
      result indicates that activation of nitric oxide synthase and thereby endogenous
      NO-formation is essential for the generation of an IL-1beta-induced febrile
      response in rats and that the suppression of IL-1beta-induced fever by treatment
      with L-NAME seems not to be caused by an inhibition of IL-6 production.

PMID- 9627107
TI  - 5-[I-125/123]lodo-3(2(S)-azetidinylmethoxy)pyridine, a radioiodinated analog of A
      85380 for in vivo studies of central nicotinic acetylcholine receptors.
AB  - The in vivo biodistribution profile of the novel nicotinic acetylcholine receptor
      (nAChR) radioligand 5-[I-125/123]Iodo-3(2(S)-azetidinylmethoxy)pyridine, [I
      125/123]-5-IA, in mouse brain was examined. This radiotracer displayed good brain
      penetration (3.1% of the injected dose (ID) in whole brain at 15 min post
      radioligand injection). Radioligand distribution was consistent with the density
      of high affinity nAChRs with highest uptake observed in the nAChR-rich thalamus
      (14.9 %ID/g at 60 min), moderate uptake in cortex (8.5 %ID/g at 60 min), and
      lowest uptake in the cerebellum (2.4 %ID/g at 60 min). Pretreatment with several
      different nAChR agonists (A-85380, (-)-nicotine, cytisine) significantly
      inhibited [I-125]-5-IA binding in all brain regions studied (P < 0.01)
      demonstrating the high specificity of the radioligand for nAChRs. Blocking doses
      of the muscarinic antagonist scopolamine and the non-competitive nAChR channel
      blocker mecamylamine had no significant effect on radioactive uptake supporting
      the in vitro selectivity of [I-125]-5-IA for the nAChR component of the
      cholinergic system. [I-125]-5-IA binding sites were shown to be saturable with
      unlabeled 5-IA. With a relatively low acute toxicity (LD50 > 3 mg/kg via
      intravenous injection in mice) and high in vivo specificity and selectivity, 5-IA
      labeled with the imaging radionuclide I-123 may prove useful for single photon
      emission computed tomography (SPECT) studies of nAChRs in human subjects.

PMID- 9627108
TI  - Involvement of MMP-1 and MMP-3 in collagen degradation induced by IL-1 in rabbit
      cartilage explant culture.
AB  - To determine whether matrix metalloproteinase-1 (MMP-1) or MMP-3 is involved in
      cartilage collagen degradation, polyclonal antibodies were separately raised
      against MMP-1 and MMP-3 and their effects on collagen degradation were assessed
      in rabbit cartilage explant culture. We found that anti-MMP-1 antibodies
      completely inhibited collagen degradation induced by the combination of
      interleukin-1 (IL-1) and plasminogen. Anti-MMP-3 antibodies showed 40% inhibition
      at maximum concentration. These results indicate that MMP-1, and possibly MMP-3,
      are involved in collagen degradation in cartilage explant culture.

PMID- 9627109
TI  - Crk protein binds to PDGF receptor and insulin receptor substrate-1 with
      different modulating effects on PDGF- and insulin-dependent signaling pathways.
AB  - We have studied the involvement of murine c-Crk, an SH2/SH3 containing adaptor
      protein, in signaling pathways stimulated by different receptor tyrosine kinases.
      We show here that c-Crk is associated with components of insulin- and PDGF
      dependent signaling pathways. Insulin treatment of murine myoblast cells induces
      the formation of stable complex of endogenous c-Crk with insulin receptor
      substrate-1 (IRS-1) mediated via the SH2 domain of Crk. The ligand dependent
      physical association of c-Crk with IRS-1 is direct. However IRS-1 is also co
      precipitated with c-Crk from quiescent L6 cells. The association of IRS-1 with c
      Crk in quiescent cells is probably not direct since Far Western blot analysis did
      not reveal the binding of neither SH2 domain nor amino-terminal SH3 domain of c
      Crk to IRS-1 from unstimulated cells. We also show that PDGF treatment of murine
      myoblast cells induces association of c-Crk with the PDGF receptor and tyrosine
      phosphorylation of c-Crk. Overexpression of c-Crk enhanced insulin- but not PDGF
      induced activation of MAP kinases when compared to parental cell lines. Thus, the
      formation of the direct IRS-1/Crk complex appears to be crucial for Crk-mediated
      insulin-induced activation of MAP kinase, whereas Crk is probably involved in
      other PDGF-induced responses. These data provide support to the hypothesis that
      insulin and PDGF employ different mechanisms for activation of MAP kinase
      cascade.

PMID- 9627110
TI  - Signalling of the Ret receptor tyrosine kinase through the c-Jun NH2-terminal
      protein kinases (JNKS): evidence for a divergence of the ERKs and JNKs pathways
      induced by Ret.
AB  - The RET proto-oncogene encodes a functional receptor tyrosine kinase (Ret) for
      the Glial cell line Derived Neurotrophic Factor (GDNF). RET is involved in
      several neoplastic and non-neoplastic human diseases. Oncogenic activation of RET
      is detected in human papillary thyroid tumours and in multiple endocrine
      neoplasia type 2 syndromes. Inactivating mutations of RET have been associated to
      the congenital megacolon, i.e. Hirschprung's disease. In order to identify
      pathways that are relevant for Ret signalling to the nucleus, we have
      investigated its ability to induce the c-Jun NH2-terminal protein kinases (JNK).
      Here we show that triggering the endogenous Ret, expressed in PC12 cells, induces
      JNK activity; moreover, Ret is able to activate JNK either when transiently
      transfected in COS-1 cells or when stably expressed in NIH3T3 fibroblasts or in
      PC Cl 3 epithelial thyroid cells. JNK activation is dependent on the Ret kinase
      function, as a kinase-deficient RET mutant, associated with Hirschsprung's
      disease, fails to activate JNK. The pathway leading to the activation of JNK by
      RET is clearly divergent from that leading to the activation of ERK: substitution
      of the tyrosine 1062 of Ret, the Shc binding site, for phenylalanine abrogates
      ERK but not JNK activation. Experiments conducted with dominant negative mutants
      or with negative regulators demonstrate that JNK activation by Ret is mediated by
      Rho/Rac related small GTPases and, particularly, by Cdc42.

PMID- 9627111
TI  - Identification of novel molecular markers which correlate with HPV-induced tumor
      progression.
AB  - High risk HPVs (human papillomaviruses) are causally involved in the development
      of cervical cancer. However, other factors, such as somatic genetic alterations
      also play a decisive role in malignant conversion of cervical keratinocytes.
      Mutations and chromosomal aberrations are known to influence the pattern of gene
      expression. Therefore we used the recently developed RT-PCR based method of
      differential display of mRNAs to detect differences in gene expression which
      correlate with tumorigenicity. Non-tumorigenic HPV16-immortalized human foreskin
      keratinocytes (HPK IA) were compared with their tumorigenic counterparts and 49
      different genes were identified which were either up- or downregulated. The
      identified genes encode proteins of the cytoskeleton and the extracellular
      matrix, the nuclear splicing apparatus, transcription regulators and membrane
      associated proteins. The expression pattern of all genes was also examined by RNA
      RNA in situ hybridization in biopsies of normal cervical epithelium, precancerous
      lesions and cancers. Two genes, C4.8 and C21.7, are of particular interest
      because their expression is upregulated in a subset of high grade precancerous
      lesions and in over 58% of cancers. These two genes may therefore be considered
      as putative progression markers. C4.8 is a new member of the transmembrane 4 (TM
      4) protein family which includes tumor-associated antigens such as CD63 and TAPA
      1, whereas C21.7 shows no significant homologies to any known genes or proteins.

PMID- 9627112
TI  - Down-regulation of T1A12/mac25, a novel insulin-like growth factor binding
      protein related gene, is associated with disease progression in breast
      carcinomas.
AB  - To define genes that are essential to the initiation and progression of breast
      cancer we utilized subtractive hybridization and differential display cloning
      techniques and isolated over 950 cDNAs from breast cell-lines derived from
      matched normal and tumor tissue. Of these, 102 cDNAs were characterized by DNA
      sequencing and Northern blot analysis. GenBank searches showed that one of these
      genes, T1A12 is identical to mac25, an insulin-like growth factor-binding protein
      related gene. Antibodies generated against the C-terminal region of the
      T1A12/mac25 protein were used to investigate its expression in 60 primary breast
      tissues. Sections of 12 benign, 16 ductal carcinoma in situ and 32 infiltrating
      ductal carcinoma specimens were examined. Strong immunoperoxidase staining was
      observed in luminal epithelial cells of normal lobules and ducts, in apocrine
      cells of cysts and fibroadenomas. Moderate to weak protein expression was found
      in hyperplastic and DCIS cells, but no specific staining was detected in invasive
      carcinoma cells. FISH mapping using a PAC clone localized the T1A12/mac25 gene to
      4q12-13. Microsatellite length polymorphism was studied using markers for 4q in
      paired normal and tumor breast tissues. Thirty-three per cent (10/30) of the
      samples were found to be polymorphic with D4S189 and D4S231 microsatellite
      markers and LOH was detected in 50% (5/10) of these informative samples. Our data
      indicate that T1A12/mac25 expression is abrogated during breast cancer
      progression concomitant with loss of heterozygosity on chromosome 4q. T1A12/mac25
      may therefore have a tumor suppressor-like function and its expression could
      indicate a disease with a more favorable status, having a better prognosis.

PMID- 9627113
TI  - Mutations in exon 7 and 8 of p53 as poor prognostic factors in patients with non
      small cell lung cancer.
AB  - This study was performed to clarify the different effects of each mutant exon of
      p53 as indicators of a poor prognosis in patients with non-small cell lung cancer
      (NSCLC). Tumor tissues of 204 patients with NSCLC were analysed; 96 tumors were
      stage I, 22 stage II, and 86 stage III. DNA was extracted from frozen specimens
      and polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP)
      and direct sequencing were performed to investigate mutations of p53 from exon 5
      to exon 8. Seventy-five patients with NSCLC (36.8%) had mutations in p53 which
      included 72 cases of missense mutations and three cases of non-missense
      mutations. The overall survival rate of patients with mutant p53 adenocarcinomas
      was strikingly worse than that of patients whose tumors had wild-type p53 (35.7%
      vs 53.8%; P=0.041), but no significant difference in survival was found in the
      patients with NSCLC and squamous cell carcinoma. Mutations in exon 5 of p53
      occurred in 33 cases (16.2%), mutation in exon 6 was detected in only one case
      (0.5%), mutations in exon 7 in 20 cases (9.8%), and mutations in exon 8 in 18
      cases (8.8%). The overall survival rate of patients with mutations in exon 7 was
      worse than that of patients with wild-type p53 in NSCLCs and adenocarcinomas
      (42.9% vs 56.0%; P=0.025 and 33.3% vs 53.8%; P=0.048, respectively), whereas the
      overall survival of patients with mutations in exon 5 was almost the same as that
      of patients with wild-type p53. In addition, the overall survival rate of
      patients with mutations in exon 8 was strikingly worse than that of patients with
      wild-type p53 in NSCLCs, adenocarcinomas and squamous cell carcinomas (22.9% vs
      56.0%; P<0.001, 19.0% vs 53.8%; P=0.004 and 33.3% vs 62.5%; P=0.042,
      respectively). Multivariate analysis with the Cox regression model of patients
      with NSCLC, adenocarcinoma and squamous cell carcinoma indicated that mutations
      in exon 8 were best correlated with the overall survival rate, followed by lymph
      node status (P<0.001, P=0.015 and P=0.006, respectively), and mutations in exon 7
      of NSCLC were also revealed to have good correlation, followed by lymph node
      status and mutations in exon 8 (P=0.031). Mutation of p53 was a poor prognostic
      factor for adenocarcinoma as described previously. Moreover, mutations in exon 8
      were more useful indicators of prognosis not only for adenocarcinoma but also for
      NSCLC. Worse overall survival of the patients with mutations in exon 8 of p53 was
      suggested to be associated with codon 273 mutations as well as mutations between
      codon 280 and 285 included into the H2 alpha helix corresponding to residues 278
      286. These results suggested that abnormal conformation of H2 alpha helix might
      play an important role not only in the loss of normal function but also in the
      acquisition of tumorigenesis. Investigation of mutations in exon 8, especially
      codon 273 mutation and mutant H2 alpha helix was considered to be a clinically
      useful approach for determining the prognosis of patients with NSCLC.

PMID- 9627114
TI  - The proliferation-associated early response gene p22/PRG1 is a novel p53 target
      gene.
AB  - The novel early response gene p22/PRG1 is linked to cell cycle entry and the
      induction of proliferation in various cell types although its exact function is
      still unknown. The p22/PRG1 promoter region contains a 20 bp sequence matching
      the consensus binding motif for the tumor suppressor protein p53. Gel shift
      assays demonstrated that p53 specifically binds to an oligonucleotide derived
      from the p53 binding site of the p22/PRG1 promoter. Chloramphenicol
      acetyltransferase (CAT) reporter gene assays confirmed that this site confers p53
      dependent transcriptional activity to the p22/PRG1 promoter. In Hela cells,
      p22/PRG1 promoter constructs induced CAT expression only when cotransfected with
      an expression plasmid for wild-type, but not for mutant p53. Similarly, CAT
      expression was inducible at the permissive (31 degrees C) but not at the non
      permissive temperature (39 degrees C) in the rat embryo fibroblast-derived cell
      line clone-6 that expresses a temperature-sensitive mutant p53. Conversion of
      this mutant p53 to a functional p53 at the permissive temperature was accompanied
      by a significant increase of endogenous p22/PRG1 mRNA level in this cell line.
      Gamma-irradiation of rat splenocytes or doxorubicin-treatment of Hela cells
      increased p53 levels followed by transcriptional activation of p22/PRG1 and
      p21/Waf1 in parallel. Our data demonstrate that p22/PRG1 transcription is induced
      by p53 during p53-dependent cell cycle arrest and apoptosis. Therefore, p22/PRG1
      represents a novel target for transcriptional activation by p53.

PMID- 9627116
TI  - IL-15 is produced by a subset of human melanomas, and is involved in the
      regulation of markers of melanoma progression through juxtacrine loops.
AB  - IL-15 is a novel cytokine active through the IL-2R/betagamma. Since several human
      melanoma cell lines display functional IL-2Rs, we studied the IL-15/melanoma
      cells interactions. Ten out of 17 melanoma cell lines express the IL-15
      transcript and four of them express levels of IL-15 mRNA similar to those
      detected in control activated monocytes. Nine out of ten cell lines also express
      two transcripts for the IL-15R alpha originated by the alternative splicing of
      exon'3'. Two melanoma cell lines, MELP and MELREO, derived from patients with
      rapidly progressive primary melanomas, co-express the two IL-15 transcripts,
      originated by alternative splicing of exon 'A'. Intracellular IL-15 protein was
      only detected in these two cells lines and it is mainly retained in the
      Endoplasmic Reticulum (ER). However, a small amount of IL-15 is also found in the
      Golgi apparatus and in the early endosomes, suggesting production and
      intercellular trafficking of endogenous IL-15 protein. Nevertheless, no
      biologically active IL-15 could be detected in the supernatant of all melanoma
      cells. The anti IL-15 blocking mAb M111 causes the up regulation of HLA Class I
      in dense MELP and MELREO cultures. These data suggest that IL-15 is probably
      active through juxtacrine loops negatively controlling HLA Class I molecules
      expression. These data offer, for the first time, a likely explanation to the
      controversial issue of IL-15 secretion and constitute a natural model for
      understanding IL-15 routing. Moreover, we identify a subset of melanoma cells
      producing IL-15, possibly involved in tumor escape mechanisms.

PMID- 9627115
TI  - Release of cell cycle constraints in mouse melanocytes by overexpressed mutant
      E2F1E132, but not by deletion of p16INK4A or p21WAF1/CIP1.
AB  - Compared to normal melanocytes, melanoma cell lines exhibit overexpression of
      hyperphosphorylated retinoblastoma tumor suppressor protein (Rb) or a marked
      decrease in, or lack of, expression of Rb. Hyperphosphorylation of Rb results in
      increased E2F-mediated transactivation of target genes and cell cycle
      progression. Using a combination of gene disruption and ectopic expression in
      growth factor-dependent mouse melanocytes, we studied the roles of E2F1 and the
      p16INK4A and p21WAF1/CIP1 CKIs (cyclin dependent kinase inhibitors) in the
      acquisition of TPA (12-O-tetradecanoyl phorbol-13-acetate)-independent growth in
      culture, a hallmark of melanomas. Surprisingly, melanocytes from p16INK4A- or
      p21WAF1/CIP1-null mice remained TPA-dependent, and disruption of p21WAF1/CIP1
      accelerated cell death in the absence of this mitogen. Disruption of E2F1 had the
      most profound effect on melanocyte growth, resulting in a fourfold decrease in
      growth rate in the presence of TPA. Furthermore, enforced overexpression of the
      DNA-binding-defective E2F1E132 mutant conferred TPA-independence upon melanocytes
      and was associated with sequestration of Rb and constitutive expression of E2F1
      target genes, including p21WAF1/CIP1. We conclude that neutralization of Rb by
      E2F1E132, but not the disruption of p16INK4A or p21WAF1/CIP1, resulted in the
      accumulation of free E2F and cell cycle progression. Thus, mechanisms other than
      the loss of p16INK4A or p21WAF1/CIP1 that activate E2F may play an important role
      in melanomas.

PMID- 9627117
TI  - Characterization of Brx, a novel Dbl family member that modulates estrogen
      receptor action.
AB  - Regulation of gene activation by the estrogen receptor (ER) is complex and
      involves co-regulatory proteins, oncoproteins (such as Fos and Jun), and
      phosphorylation signaling pathways. Here we report the cloning and initial
      characterization of a novel protein, Brx, that contains a region of identity to
      the oncogenic Rho-guanine nucleotide exchange (Rho-GEF) protein Lbc, and a unique
      region capable of binding to nuclear hormone receptors, including the ER. Western
      and immunohistochemistry studies showed Brx to be expressed in estrogen
      responsive reproductive tissues, including breast ductal epithelium. Brx bound
      specifically to the ER via an interaction that required distinct regions of ER
      and Brx. Furthermore, overexpression of Brx in transfection experiments using an
      estrogen-responsive reporter revealed that Brx augmented gene activation by the
      ER in an element-specific and ligand-dependent manner. Moreover, activation of ER
      by Brx could be specifically inhibited by a dominant-negative mutant of Cdc42Hs,
      but not by dominant negative mutants of RhoA or Rac1. Taken together, these data
      suggest that Brx represents a novel modular protein that may integrate
      cytoplasmic signaling pathways involving Rho family GTPases and nuclear hormone
      receptors.

PMID- 9627118
TI  - Human tumor-derived p53 proteins exhibit binding site selectivity and temperature
      sensitivity for transactivation in a yeast-based assay.
AB  - p53 is a sequence-specific transcriptional activator with a number of known
      target genes which contain p53-responsive elements. Mutations in p53 have been
      identified within its sequence-specific DNA binding domain in more than half of
      all human tumors, although a subset of tumor-derived p53 mutants have retained
      the ability to bind DNA and activate transcription under certain conditions. In
      order to broaden our understanding of this transactivating ability, we examined
      the efficacy by which p53 mutants bind to and activate reporters in an
      Saccharomyces cerevisiae-based assay. Analysis of 19 human tumor-derived p53
      mutants, spanning the DNA binding domain of p53 and including the 'hot-spot'
      class, revealed a broad array of transcriptional transactivation abilities at 24
      degrees C, 30 degrees C and 37 degrees C, despite the fact that each mutant had
      originally been identified as being inactive for transactivation in yeast against
      a single p53-responsive RGC site-containing reporter. One class of mutants
      (P177L, R267W, C277Y and R283H) retained wild-type or near wild-type activity
      that is binding site-selective, even at physiological temperature (37 degrees C).
      Another class of mutants (V143A, M1601/A161T, H193R, Y220C and 1254F), all
      positioned for maintaining the beta-scaffold of p53, also retained selective
      activity, but preferentially at sub-physiological temperatures (24 degrees and 30
      degrees C). Strikingly, however, in contrast to the other tumor derived mutants,
      all of the previously identified 'hot-spot' mutants were completely inactive with
      all sites tested. Moreover, a double mutant, L22E/W23S, located within the
      activation region and previously shown to be transcriptionally inactive in
      fibroblasts, retained wild-type or near wild-type binding site-selective activity
      in yeast. Finally, we found that transcriptional activity in vivo does not
      necessarily correlate with DNA binding in vitro.

PMID- 9627119
TI  - The Bmi-1 oncoprotein interacts with dinG and MPh2: the role of RING finger
      domains.
AB  - Experimentally-induced mutations in the C3HC4 RING finger domain of the Bmi-1
      oncoprotein block its ability to induce lymphomas in mice. In this report, the
      role of the Bmi-1 RING finger in mediating protein-protein interactions is
      examined using the yeast two-hybrid system. Bmi-1 interacts directly with the
      RING finger protein dinG/RING1B. Heterodimerization of the two proteins requires
      the intact RING finger structures of both Bmi-1 and dinG. Although the RING
      finger domains are necessary for dimerization, they are not sufficient for this
      process as residues outside the C3HC4 motif are also required. Thus, binding
      specificity may be partly conferred by residues outside the RING motif. Both Bmi
      1 and dinG interact with the Polyhomeotic protein MPh2 through binding domains
      apart from the RING finger. The data suggest a model whereby Bmi-1, dinG, and
      MPh2 form a stable heterotrimeric complex in which each protein contributes to
      the binding of the others.

PMID- 9627120
TI  - Histone deacetylase associated with mSin3A mediates repression by the acute
      promyelocytic leukemia-associated PLZF protein.
AB  - The PLZF gene was identified first by its fusion with the retinoic acid receptor
      alpha gene in the t(11;17) translocation associated with a retinoic acid
      resistant form of acute promyelocytic leukemia (APL). It encodes a kruppel-like
      zinc finger protein with a POZ domain shared with a subset of regulatory proteins
      including the BCL6 leukemogenic protein. PLZF, like BCL6, strongly represses
      transcription initiated from different promoters. Here we show that PLZF
      associates in vitro and in vivo with the Mad co-repressor mSin3A and the histone
      deacetylase HDAC1. Two domains in PLZF and the PAH1 structure of mSin3A mediate
      these interactions. Trichostatin A, a specific inhibitor of histone deacetylases,
      significantly reduces PLZF repression. These data strongly suggest that, like
      nuclear receptors and Mad, PLZF represses transcription by recruiting a histone
      deacetylase through the SMRT-mSin3-HDAC co-repressor complex. We also show that
      BCL6 associates with HDAC1 indicating that this type of regulation might be
      common to POZ/Zinc finger proteins involved in human leukemias. This work
      supports a role for deregulated histone deacetylation in the development of both
      lymphoid and myeloid neoplasia in human and suggests that targeted histone
      deacetylase inhibitors may be useful for treatment of certain types of
      malignancies.

PMID- 9627121
TI  - Allelic deletion at 11q23.3-q25 is an early event in cervical neoplasia.
AB  - Twenty per cent of cervical intraepithelial neoplasias-III (CIN-III) progress to
      invasive cancer. Human papillomavirus (HPV) infection alone does not determine
      progression. CIN-III lesions were collected from 161 women. Each tissue was
      microdissected into a maximum of 32 contiguous units and assayed at multiple
      microsatellite loci on chromosome 11q, a region frequently deleted in invasive
      cervical and other cancers. Eight of 108 informative cases (7%) had 11q23.3-q25
      deletions; focally intra-lesional in six (one with focal loss of alternate
      alleles), and pan-lesional in two cases. Hence, 11q deletion can occur early in
      cervical neoplasia, and possibly predisposes to invasion.

PMID- 9627122
TI  - Induction of gut mucosal immune responses: importance of genetic background and
      Th1/Th2 cross-regulation.
AB  - The reciprocal regulation of T-helper cell (Th) subsets is widely documented in
      various animal models of infectious diseases. In this study IFN-gamma/IL-4 double
      knockout (DKO) mice were used to analyse the role of Th subsets in mucosal immune
      responses. We found that the DKO mice had normal IgA differentiation but impaired
      induction of specific gut mucosal antibody responses after oral immunization
      using cholera toxin adjuvant. Both Th1 and Th2 responses were reduced compared
      with wild-type mice. Despite the absence of both IFN-gamma and IL-4 in the DKO
      mice the overall results were similar to previous observations in IFN-gamma
      receptor-knockout (IFN-gammaR-/-) mice and did not suggest a strict cross
      regulation of the two Th subsets in the gut mucosa. To further examine the role
      of IFN-gamma in mucosal immunity we compared two different mouse strains lacking
      IFN-gamma, i.e. IFN-gamma-/- (C57BL/6) and IFN-gammaR-/- mice (129/Sv). We found
      that IFN-gammaR-/- mice exhibited reduced mucosal antibody responses and
      decreased Th1 and Th2 activity after oral immunization, while IFN-gamma-/- mice
      had intact antibody responses and increased Th2 responses. Thus, genetic
      differences were found to critically affect the development of a specific gut
      mucosal immune response. An enhanced Th2 activity in the Peyer's patches
      following oral immunization was associated with an ability to mount strong
      intestinal IgA immunity.

PMID- 9627123
TI  - Recurrent herpes simplex virus-induced erythema multiforme: different HLA-DQB1
      alleles associate with severe mucous membrane versus skin attacks.
AB  - In some individuals a local herpetic lesion precipitates a generalized
      inflammation of the skin, designated as erythema multiforme (EM). We determined
      the frequencies of the immune response genes of the HLA system by molecular HLA
      class II typing in 46 patients with EM and in many of their family members.
      Allele frequencies were correlated with disease form and disease-inducing
      factors. We found that specific complications of HSV infection occur
      preferentially in patients with certain HLA-DQB1 alleles. In 21 of the 46
      patients EM was induced by recurrent HSV infection. Thirteen of these patients
      showing only minor or no involvement of mucous membranes had the HLA allele
      DQB1*0302 (phenotype frequency 61.9% versus 18.8% in controls, p corr = 0.0008)
      and all three patients with major involvement of mucous membranes had the rare
      HLA allele DQB1*0402 (phenotype frequency in controls 6,4%, p corr = 0.017).

PMID- 9627124
TI  - Natural killer cells and recognition of MHC class I molecules: new perspectives
      and challenges in immunology.

PMID- 9627125
TI  - The simulation of density-dependent effects in the recirculation of T
      lymphocytes.
AB  - T-lymphocyte recirculation appears to be slower in nude or irradiated rats as
      compared with normal rats. A mathematical model of T-lymphocyte recirculation
      that incorporates interactions between T cells and dendritic cells in the
      lymphoid tissue is presented. It is shown that these interactions are able to
      explain the differences in recirculation times between normal and nude or
      irradiated rats, and also the time-scales seen in long-term thoracic duct
      cannulations.

PMID- 9627126
TI  - Immunobiological studies on experimental visceral Leishmaniasis. V. The I-A(Bm12)
      mutation specifies resistance to infection.
AB  - The I-A(Bm12) mutation of the I-A beta subunit converted Leishmania donovani
      susceptible C57BL/6 (B6) mice into the relatively resistant B6C-H-2 Bm12 (Bm12)
      strain. The relative resistance was reflected not only in the reduced splenic and
      hepatic parasite burden in Bm12 (compared with B6) but also by the ability of
      Bm12 mice to mount a T-cell proliferative response to parasite antigens. Assay of
      antileishmanial antibody (immunoglobulin G (IgG)2a and IgG1) in the sera of
      infected mice showed that in Bm12 mice the predominant isotype was IgG2a, rather
      than IgG1, whereas a similar level of both isotypes were found in B6 mice. From
      the serum immunoglobulin isotype titre it appeared that the antileishmanial T
      cell response was biased towards a T helper (Th) 1 response in Bm12 mice whereas
      it was a mixed Th1 and Th2 response in B6 mice. These observations provide
      credence to the notion that polymorphism in class II major histocompatibility
      complex (MHC) molecules is responsible for the difference in the disease
      phenotype.

PMID- 9627127
TI  - Acquisition of interleukin-5 secretion by human naive T-helper cells is regulated
      by distinct signals from both the T-cell receptor/CD3 complex and CD2.
AB  - We developed a human naive T-helper (Th) cell differentiation model with anti-CD3
      monoclonal antibody (MoAb), using a B-cell line as source of costimulation. In
      this system, we examined the contribution of the T-cell receptor (TCR)/CD3
      derived signals and that of lymphocyte function-associated antigen-1 (LFA-1) and
      CD2 in regulating Th-cell subset differentiation. We found that lowering the
      level of anti-CD3 MoAb decreased tumour necrosis factor-alpha (TNF-alpha)
      production, while increasing secretion of the Th2 cytokines, interleukin-5 (IL-5)
      and interleukin-13 (IL-13). Secretion of interferon-gamma (IFN-gamma) was not
      influenced by the strength of the anti-CD3 signal. Under conditions where Th0
      cells are generated, co-culture with anti-CD2 F(ab')2 MoAb led to the generation
      of Th cells that secreted 30-35% less IL-5, while not affecting secretion of IFN
      gamma or granulocyte-macrophage colony-stimulating factor (GM-CSF). By contrast,
      anti-CD18 MoAb F(ab')2 inhibited IFN-gamma and GM-CSF levels only in the primary
      stimulation, but did not affect cytokine levels after restimulation. Neither anti
      CD2 nor anti-CD18 F(ab')2 MoAbs could alter cytokine secretion profiles of
      peripheral blood-derived memory/effector Th cells. Our results indicate that
      acquisition of IL-5 secretion capability by Th cells is regulated mainly by
      signals transduced by the TCR/CD3 complex and by the presence of interleukin-4
      (IL-4), while the CD2/LFA-3 pathway plays an additional, but minor, role. These
      regulatory CD2-derived signals, however, are distinct from those generated by the
      TCR/CD3 complex.

PMID- 9627128
TI  - Adjuvant is the major parameter influencing the isotype profiles generated during
      immunization with a protein antigen, the Schistosoma mansoni Sm28-GST.
AB  - We have previously shown that immunization of mice with the vaccine candidate,
      the 28-kDa glutathione-S-transferase of Schistosoma mansoni (Sm28-GST), in alum
      or complete Freund's adjuvant, or with recombinant Salmonella typhimurium
      expressing Sm28-GST, induced type 2, mixed, or type 1 immune responses,
      respectively. In the present study we examined whether the genetic background,
      the dose and the route of antigen administration could modulate the profile of
      the immune response induced during these immunizations. Our results show that the
      nature of the adjuvant is the major factor that determines the profile of the
      response. Surprisingly, the genetic background did not influence the response,
      while the route of immunization, and to a lesser extent the dose of the antigen,
      weakly modulated the adjuvant-dependent orientation of the immune response.

PMID- 9627129
TI  - Internalization of Mycobacterium bovis Bacillus Calmette-Guerin into osteoblast
      like MC3T3-E1 cells and bone resorptive responses of the cells against the
      infection.
AB  - Mycobacterium bovis BCG (BCG) is a live vaccine used worldwide against
      tuberculosis. However, it has unfavourable side effects such as osteitis or
      osteomyelitis, and these sometimes lead to vertebral caries in some patients as a
      result of bone resorption. Osteoblasts might play a role in the bone resorption
      caused by BCG infection, because they are central cells in bone metabolism.
      Cultured osteoblast-like cell lines (MC3T3-E1) derived from C57BL mice
      susceptible to BCG infection cells were infected with BCG at several doses.
      Interestingly, internalization of BCG-enveloped phagosome-like membrane in
      osteoblast-like cells were observed by transmission electron microscopy (TEM).
      Owing to infection, the proliferation and alkaline phosphatase activity of the
      osteoblast-like cells were reduced in a dose-dependent manner. On the other hand,
      interleukin (IL)-6 production was considerably enhanced by infection. These
      results suggest that BCG infects osteoblasts, suppressing their proliferation and
      differentiation and inducing bone resorption, which may be related to
      osteitis/osteomyelitis and bone caries caused by BCG infection.

PMID- 9627130
TI  - Vaccine-induced Th1-type responses are dominant over Th2-type responses in the
      short term whereas pre-existing Th2 responses are dominant in the longer term.
AB  - The effect of adjuvant on induction of human papillomavirus type 16 E7 protein
      specific cytotoxic T lymphocytes (CTL) and immunoglobulin G (IgG)2a antibody was
      studied in C57BL/6 J mice immunized with various adjuvants and E7 protein. Quil-A
      adjuvant, but not complete Freund's adjuvant (CFA) or Algammulin, induced a T
      helper 1 (Th1)-type response to E7, which was characterized by CTL activity
      against a tumour cell line transfected with E7 protein and by E7-specific IgG2a.
      All tested adjuvants elicited comparable levels of E7-specific IgG1. The longest
      duration and greatest magnitude of CTL response was seen following two
      immunizations with the highest dose of E7 and Quil-A. Simultaneous immunization
      with a Th1 and a T helper 2 (Th2)-promoting adjuvant gave a Th1-type response.
      However, E7 and Quil-A were unable to induce a Th1-type response (as measured by
      the inability to generate anti-E7 IgG2a antibody) in animals with a pre-existing
      Th2-type response to E7. These results suggest that saponin adjuvants may be
      suitable for immunotherapy in humans where a Th1-type response is sought,
      provided that there is no pre-existing Th2-type response to the antigen.

PMID- 9627131
TI  - CD4-CD8-C.B-17 SCID thymocytes enter the CD4+CD8+ stage in the presence of
      neonatally grafted T cells.
AB  - The aim of this work was to study the selection of donor T cells and their
      influence on thymic development in C.B-17 scid/scid (severe combined
      immunodeficient; SCID) mice during chronic graft-versus-host disease (GVHD).
      Recipient SCID mice (H-2d), neonatally grafted with allogeneic peripheral T cells
      from CBA/J strain (H-2k) of mice, only developed a mild acute GVHD, and were, at
      the chronic stage, devoid of pathological symptoms. Thymic cell numbers of
      injected mice differed from 10(5) to 1.2 x 10(7) at 2-3 weeks post-injection
      (p.i.), and from 4 x 10(5) to 8.5 x 10(7) at 2 months p.i. In these mice, the
      thymus size was correlated to the CD4-CD8- (double negative; DN) to CD4+CD8+
      (double positive; DP) cell ratio, where at 2 months p.i., 8 out of 16 treated
      SCID mice contained 5 x 10(6) cells or more and also possessed the highest
      frequencies of endogenous DP cells (25-95%). In contrast to previous findings,
      peripheral donor T cells from allogeneic and syngeneic mice, infiltrating the
      host thymus, had a positive effect on the development of endogenous DP
      thymocytes. Furthermore, these thymocytes were developmentally blocked at the DP
      stage, occasionally in combination with the expression of CD25, CD44 and CD117
      but in the absence of T-cell receptor (TCR) expression. Also, at this time-point,
      the CBA/J donor TCR Vbeta repertoire was equal to that of normal CBA/J mice, but
      purified responding donor cells were proliferatively inhibited against H-2d
      stimulators in ex vivo mixed lymphocyte cultures. In contrast, the same
      responders showed a pronounced proliferation against syngeneic H-2Kk stimulators,
      suggesting either a reversion from anergy of autoreactive CBA/J T cells or a vast
      expansion of multiple self-reactive T-cell clones, when parked in a milieu with a
      lower concentration of self-antigens.

PMID- 9627132
TI  - Chemical denaturation of ovalbumin abrogates the induction of oral tolerance of
      mouse reaginic antibody responses.
AB  - The effect of chemical denaturation of ovalbumin (OVA) on the induction of oral
      tolerance of reaginic antibody responses was studied. Both urea-denatured OVA (UD
      OVA) and carboxymethylated UD-OVA (CM-OVA) were purified by centrifugation. When
      compared with OVA and UD-OVA, CM-OVA had the least sensitizing capacity and
      allergenicity in IgE responses to OVA. BALB/c IgE, IgG1 and IgG antibody
      responses were suppressed by OVA, but not by UD-OVA or CM-OVA, fed prior to
      sensitization with OVA, UD-OVA, or CM-OVA in alum, respectively. The priming
      effect of specific IgG and IgG1 antibody responses was induced by CM-OVA fed
      prior to sensitization with OVA or CM-OVA. The proliferation of BALB/c spleen
      cells and their secretion of T helper type 2 (Th2) cytokines interleukin-4 (IL-4)
      and IL-5 were also orally tolerized by OVA, but not by denatured OVA. Although
      denatured OVA is hypoallergenic, the present result indicates that denaturation
      of a soluble protein prevents the induction of oral tolerance of Th2 responses.

PMID- 9627133
TI  - Binding of properdin to solid-phase immune complexes: critical role of the
      classical activation pathway of complement.
AB  - The capacity of serum to support deposition of C3, properdin and factor B was
      studied by enzyme-linked immunosorbent assay using solid-phase immune complexes
      (IC) for activation of complement. Deposition of C3 and properdin occurred in
      fairly dilute normal human serum (NHS), but factor B uptake was hardly
      detectable. Alternative pathway-mediated deposition of C3 with slow kinetics was
      demonstrated in C2-deficient serum and in NHS depleted of C1q, factor D and
      properdin (C1qDP-depleted serum) after reconstitution with factor D and
      properdin. Efficient uptake of properdin required a functional classical pathway,
      in the presence of which C3 and properdin were rapidly deposited onto the IC.
      Judging from findings in C3-deficient serum, factor I-deficient serum, and C1qDPB
      depleted serum, the uptake of properdin was strictly C3-dependent, and did not
      require the presence of factors B and D. Thus, C3b fixed to IC was the principal
      ligand for properdin in the assay. The findings could have biological
      implications relating to complement-mediated modification of immune complexes in
      disease.

PMID- 9627134
TI  - Differential adhesion molecule expression on porcine mononuclear cell
      populations.
AB  - Adhesion molecule expression was analysed on porcine blood and lymphoid organ
      CD4+ CD8 naive T helper (Th) lymphocytes, CD4+CD8+ memory Th lymphocytes
      (particular to the pig), CD4-CD8high cytotoxic T (Tc) lymphocytes, CD4 CD8low NK
      cells (CD3- in the pig), CD4-CD8- T-cell receptor-gammadelta-positive
      (TCRgammadelta+) lymphocytes, B lymphocytes and monocytes. While CD44 expression
      was relatively homogeneous amongst mononuclear cells, differences were noted for
      the integrins. Blood naive Th lymphocytes were CD49d(low)CD11a(low), as were
      splenic naive Th cells; blood memory Th lymphocytes were CD49d(high)CD11a(low),
      splenic memory Th cells were CD49d(high)CD11a(high) with a CD49d(high)CD11a(low)
      subpopulation; blood Tc lymphocytes were mainly CD49d(low)CD11a(low), and splenic
      cells were CD49d(high) CD11a(high). Lymph node lymphocytes were more homogeneous
      in their integrin expression. These were relatively CD49d(low)CD11a(low), except
      the memory Th lymphocytes which had higher integrin expression. B lymphocytes
      related to the majority of integrin(low) T cells, while monocytes and NK cells
      were CD49d(high) CD11a(high); gammadelta T lymphocytes showed variable CD49d
      expression but a CD11a(high) phenotype. CD49d(high) CD11a(high) co-expression was
      found, and this phenotype was typical of, but not exclusive to, CD25+ (activated)
      lymphocytes. These results demonstrated that porcine memory Th lymphocytes and NK
      cells, as well as activated cells, would have increased integrin-dependent
      activities compared with naive Th lymphocytes, and integrin-dependent reactions
      would probably vary between blood and lymphoid organ cells.

PMID- 9627135
TI  - Characterization of local memory cells in stage-classified pulmonary
      tuberculosis: preliminary observations.
AB  - Immunophenotype analysis and proliferative responses were investigated in
      bronchoalveolar lavage (BAL) cells from 21 patients with stage-classified
      tuberculosis: six with localized pulmonary infiltrate (LPI); seven with diffuse
      pulmonary infiltrate (DPI); and eight with pleural effusions (PE).
      Bronchoalveolar lavage cells from these patients contained a high number of
      cells/ml. The macrophage number was significantly lower in the DPI group (P <
      0.05) compared to the LPI or PE groups. Conversely, neutrophils were markedly
      increased in DPI patients compared to LPI (P < 0.01) and PE (P < 0.01) patients.
      Lymphocyte infiltration (97.7 +/- 2.3% CD3+, > 83% alphabeta+ and CD4+ > CD8+)
      was observed in the three groups. A significant increase in the number of total
      lymphocytes (P < 0.01) and CD4+ cells (P < 0.05) was observed in the LPI group
      compared to the PE group. In the LPI group CD4+CD45RO+ cell infiltration was
      higher than CD4+CD45RA+ cells (P < 0.001), contrasting to similar numbers of
      these subpopulations in the DPI group. Lymphocytes from three out of three LPI
      patients (alphabeta+CD4+CD45RO+) responded against tuberculin purified protein
      derivative contrasting to the unresponsiveness of five patients with either DPI
      or PE. This impaired response was reverted in two out of five patients by using
      peripheral blood monocytes instead of alveolar macrophages. It is suggested that,
      in humans, alphabetaCD4+CD45RO cells are the main lymphocyte type involved in the
      initial local cell-mediated immune response against Mycobacterium tuberculosis.

PMID- 9627136
TI  - Immunomodulation of Chiclero's ulcer. Role of eosinophils, T cells, tumour
      necrosis factor and interleukin-2.
AB  - The progression of cutaneous leishmaniasis is controlled largely by cell-mediated
      immunity. Two subpopulations of CD4+ T cells exist that control healing or
      immunopathology of murine and, perhaps, human leishmaniasis. To better understand
      the immunological pathways controlling outcome of the human disease, we analysed
      the pattern of tumour necrosis factor (TNF) and interleukin-2 (IL-2), both of
      which were present in the sera of humans with active or healed chiclero's ulcer,
      in relation to the development of delayed-type hypersensitivity (DTH) responses
      and leucocyte counts in peripheral blood. Increased serum levels of IL-2 and TNF
      alpha were apparent only in individuals with active lesions. All individuals with
      localized cutaneous leishmaniasis developed a strong DTH. The number of T cells
      was lower in the blood of diseased individuals and the CD4/CD8 ratio was reduced
      (from 1.5 to 1.0) when compared with the control group. However, diseased and
      recently cured individuals developed eosinophilia. We conclude that important
      alterations of the immune response exists in humans suffering from this normally
      self-healing infection.

PMID- 9627137
TI  - An immunoaffinity-purified Trypanosoma cruzi antigen suppresses cellular
      proliferation through a TGF-beta-mediated mechanism.
AB  - Two subfractions with opposite immunological properties were obtained from the
      flagellar antigens (FF) of Trypanosoma cruzi epimastigotes by immunoaffinity
      chromatography. The ligand-bound material (Ag 123) contained four polypeptide
      bands of 97, 55, 38 and 14 kDa. The nonretained flow-through (FT), induced a
      potent proliferation of murine naive splenocytes. In contrast, Ag 123 inhibited
      the proliferative capacity of the FT as well as the proliferation mediated by the
      mitogen Concanavalin A (Con A). The suppressive effect of Ag 123 on the Con A
      mediated proliferation was neutralized by an anti-TGF-beta monoclonal antibody.
      Both Ag 123 and FF stimulated high serum levels of TGF-beta in injected mice. Ag
      123 also induced in vitro secretion of TGF-beta by murine splenocytes. These
      results demonstrate that Ag 123 is a potent stimulator of TGF-beta both in vivo
      and in vitro. Oligopeptides derived from the 38 kDa protein present in Ag 123
      showed homology with human and rat alpha-fetoproteins (AFP). Ag 123 seems to have
      a key role in the immunosuppression that develops during early stages in the
      infection with T. cruzi.

PMID- 9627138
TI  - Chlamydia pneumoniae-specific cell-mediated and humoral immunity in healthy
      people.
AB  - In this work, cell-mediated immunity to Chlamydia pneumoniae was studied in 157
      healthy individuals using lymphoproliferative assay and serum antibodies were
      analysed by microimmunofluorescence techniques. The C. pneumoniae-specific IgG
      antibodies were elevated more frequently and the geometric mean titres for IgG
      (67.5 versus 44.1; P = 0.05) and IgA (14.9 versus 11.3; P = 0.025) antibodies
      were significantly higher in males than in females. However, no gender-dependent
      differences were observed in cellular reactivity to C. pneumoniae, since the
      median cellular responses were similar (stimulation indices 7.5) in men and
      women. Although the cell-mediated and humoral responses to C. pneumoniae did not
      correlate clearly, elevated IgG antibodies were associated with slightly higher
      lymphocyte proliferation in comparison to all subjects (15.5 versus 7.5) and
      significantly stronger in comparison to those with persistently elevated IgA (>
      80) antibodies (15.5 versus 3.5; P = 0.023). Further studies are needed to
      evaluate a possible role of reduced cellular reactivity in the cause of chronic
      C. pneumoniae infection.

PMID- 9627139
TI  - Has hospital mortality from acute myocardial infarction been markedly reduced
      since the introduction of thrombolytics and aspirin? European Secondary
      Prevention Study Group.
AB  - OBJECTIVES: There are conflicting views on how hospital mortality with respect to
      acute myocardial infarction (AMI) has changed since the introduction of
      thrombolytics and aspirin. Our purpose therefore was to explain this by studying
      hospital mortality in a nonselected AMI population. and then assess how patients
      allocated to different treatment groups contribute to overall mortality. DESIGN:
      Extensive data were collected on all AMI patients admitted to the 10 hospitals in
      health region 1 (population 850,000) in Norway during a 2 month period. A
      protocol approved by the European Secondary Prevention Study Group was used.
      RESULTS: Of the 487 patients, 32% received thrombolytics, 72% aspirin and 22%)
      none of the treatments. Average in-hospital mortality was 18%. Mortality within
      the different groups was as follows: no thrombolytics nor aspirin group 35.0%
      (39/111), aspirin group 13.7%, (30/218), thrombolytics group 17.3% (4/23), and
      thrombolytics plus aspirin group 11.0% (15/135). The characteristics of the
      nontreated group compared to the aspirin and aspirin plus thrombolytics groups
      were more females, older, increased frequency of previous AMI, left ventricular
      failure, cardiopulmonary resuscitation, history of stroke and peptic ulcer, and
      electrocardiogram (ECG) findings other than ST elevation. CONCLUSION: In a
      nonselected AMI population, a patient group receiving neither thrombolytics nor
      aspirin contributed most significantly to an overall high mortality. This
      indicates a modest reduction in total AMI mortality after the new therapies were
      introduced, as the mortality for this group, with a high risk profile, has
      presumably remained unchanged.

PMID- 9627140
TI  - Abnormal metabolism of free fatty acids in hypertriglyceridaemic men: apparent
      insulin resistance of adipose tissue.
AB  - OBJECTIVE: There is growing evidence that endogenous hypertriglyceridaemia is
      frequently accompanied by a state of insulin resistance. The present study was
      performed to determine whether patients with primary endogenous
      hypertriglyceridaemia commonly have abnormalities in plasma concentrations and
      turnover rates of free fatty acids (FFA), which could reflect a state of insulin
      resistance in adipose tissue and could account for raised plasma triglycerides.
      DESIGN: Hypertriglyceridaemic and normotriglyceridemic control patients underwent
      measurements of plasma concentrations and turnover rates of FFA. Fat weights in
      both groups were determined by hydrodensitometry, and fat distribution was
      assessed by skin-folds and measurement of waist and hip circumferences. Other
      measurements included plasma glucose, insulin, lipids, and lipoproteins.
      SUBJECTS: Fifteen men with normal plasma triglycerides and 21 men with primary
      endogenous hypertriglyceridaemia were studied. Men in both groups varied in body
      weights and total fat weights, but total fat weights were entirely overlapping
      for the two groups. Waist-to-hip ratios and waist circumferences also were
      similar for the two groups. RESULTS: For any total body fat content or waist
      circumference, most hypertriglyceridaemia patients had higher mean plasma
      concentrations of FFA and higher turnover rates (flux) for FFA than did
      normotriglyceridemic patients. Hypertriglyceridaemic patients also had higher
      fasting insulin concentrations for a given body fat content. In general, both FFA
      flux and plasma insulin levels were positively correlated with plasma
      concentrations of triglyceride and inversely with high density lipoprotein (HDL)
      cholesterol. CONCLUSIONS: These studies indicate that many patients with primary
      endogenous hypertriglyceridaemia have increased flux of FFA and hyperinsulinemia
      that cannot be explained either by increased total body fat content or by greater
      waist circumferences than observed in normotriglyceridemic patients.

PMID- 9627141
TI  - Exercise-induced aortic flow parameters in early postmenopausal women and middle
      aged men.
AB  - OBJECTIVE: Exercise Doppler echocardiography has been recognised as an accurate
      method for the assessment of left ventricular function in patients with coronary
      artery disease. Gender differences in aortic flow parameters during exercise have
      not been well established. The aims of this study were to compare basal ejection
      Doppler indexes in healthy early postmenopausal women with those of men, and to
      assess the effects of both isometric and dynamic exercises on these parameters.
      DESIGN: Intergroup comparison between early postmenopausal women and middle-aged
      men. SUBJECTS: Fifteen healthy women with a mean age of 55 (SD 5) years and 15
      healthy men aged 52 (SD 4) were evaluated. SETTING: Women were recruited from a
      menopause clinic and men from a primary cardiovascular prevention program at a
      cardiac rehabilitation institute. INTERVENTIONS: Isometric exercise was performed
      with a 2-hand bar dynamometer, and dynamic exercise with a supine ergometer. Echo
      Doppler examination was performed at rest and at peak isometric and dynamic
      exercise with a pulsed Doppler transducer. RESULTS: Both types of exercise
      resulted in higher values of hemodynamic parameters in the women, with most
      figures reaching statistical significance. Most aortic flow parameters during
      rest and exercise were also significantly higher in the women. CONCLUSIONS: The
      unexpected higher values in hemodynamic and aortic flow parameters in early
      postmenopausal women as compared with middle aged men may shed light on a
      peculiar aspect of gender differences in cardiovascular function, perhaps
      specific to this age group and related to menopausal transition.

PMID- 9627142
TI  - Role of routine transthoracic echocardiography in evaluation and management of
      stroke.
AB  - OBJECTIVE: To determine the value of routine transthoracic echocardiography in
      patients with cerebral ischemia without known cardiac disease. DESIGN: The
      literature from 1990 to 1995 was searched and relevant bibliographies from these
      papers reviewed. Articles reporting the prevalence and/or risk of stroke for
      myxoma, vegetation, mitral stenosis, left atrial thrombus, left ventricular
      thrombus or cardiomyopathy, patent foramen ovale, and atrial septal aneurysm were
      used. Prevalences and recurrent stroke risk were examined for adult patients less
      than and greater than 45 years. RESULTS: Both the prevalence of transthoracic
      echocardiographic findings and recurrent risk of stroke differ by age. The
      finding of a patent foramen ovale can be expected in nearly half of younger
      patients with stroke, whilst transthoracic echo can be expected to yield no
      relevant lesion in three quarters of patients > 45 years. Warfarin
      anticoagulation appears beneficial in patients with mitral stenosis, left atrial
      thrombus, left ventricular thrombus, and left ventricular dysfunction, but is of
      unproven benefit for patent foramen ovale, atrial septal aneurysm, or in the
      absence of a risk-associated abnormality. CONCLUSION: For most transthoracic echo
      findings in stroke, optimal management strategies have not been well defined.
      Future research is needed to evaluate the appropriate therapeutic approaches.

PMID- 9627143
TI  - Individuals with high total cholesterol/HDL cholesterol ratios are insulin
      resistant.
AB  - OBJECTIVES: To define the pathophysiologic characteristics of patients at high
      risk for coronary heart disease due to an increased ratio of total cholesterol
      (TC) to high density lipoprotein-cholesterol (HDL-C). DESIGN: Cross-sectional.
      SETTING: Clinical Research Center. SUBJECTS: One hundred-20 healthy, non
      diabetic, normotensive, volunteers were screened for this study. From this pool,
      40 individuals (20 females and 20 males) with the highest and the lowest TC/HDL-C
      ratios were selected for comparison. MAIN OUTCOME MEASURES: Values for body mass
      index (BMI), ratio of waist to hip girth (WHR), and blood pressure were obtained
      on all patients. In addition, measurements were made of fasting lipid and
      lipoprotein concentrations, plasma glucose and insulin responses to an oral
      glucose challenge, and insulin resistance as assessed by the insulin suppression
      test. RESULTS: Age, BMI, and WHR were the same in the two groups. However, the
      group with a high TC/HDL-C ratio had higher (P < 0.05) systolic and diastolic
      blood pressures. In addition, patients with a high TC/HDL-C ratio had
      significantly higher (P < 0.001) very low density (VLDL) and low density
      lipoprotein (LDL)-cholesterol concentrations and lower HDL-cholesterol
      concentrations, with significant (P < 0.001) correlations between the TC/HDL-C
      ratio and VLDL (r = 0.60), LDL (r = 0.54), and HDL (r = -0.73) cholesterol
      concentrations. Patients with a high TC/HDL-C ratio were also significantly (P <
      0.05-0.001) more insulin resistant, glucose intolerant with a greater plasma
      insulin response to oral glucose, and hypertriglyceridemic. CONCLUSIONS: The
      results indicate that an increase in LDL-cholesterol concentration is not
      necessarily the major contributor to a high ratio of TC/HDL-C. Furthermore,
      individuals with this epidemiologic designation are insulin resistant, and liable
      to all the other abnormalities associated with this metabolic defect.

PMID- 9627144
TI  - Erythrocytic protein kinase C activity in primary hypertension.
AB  - OBJECTIVES: Increased protein kinase C activity has been reported in erythrocytes
      from patients with primary hypertension and also from hypertensive rats. In this
      phenomenological study, we investigated whether a possible increased activity was
      the result of an augmented amount of enzyme molecules or a more active enzyme.
      DESIGN: Collect blood samples, separate erythrocytes from other blood cells.
      After partial purification of protein kinase C in the erythrocyte lysate, assay
      the enzyme activity under optimal conditions using a specific peptide substrate.
      SETTING: Central Hospital in Eskilstuna and University Hospital in Uppsala,
      Sweden. SUBJECTS: Healthy individuals: 47 persons (20 women and 27 men). Ten
      patients with untreated primary hypertension. MAIN OUTCOME MEASURES: Erythrocytes
      were separated from leucocytes and platelets by passing through a cellulose
      column followed by repeated washings. Some proteins in the erythrocyte lysate
      interfering with protein kinase C assay were removed by chromatography on DEAE
      cellulose. RESULTS: The mean protein kinase C activity in erythrocytes from
      healthy individuals was 0.18 +/- 0.02 pmol [32P]phosphate min(-1) x 10(6) cells,
      regardless of sex and age. The corresponding value for patients with primary
      hypertension was 0.16 +/- 0.04 pmol [32P]phosphate min(-1) x 10(6) cells.
      CONCLUSIONS: The amount of protein kinase C, measured as the activity at optimal
      assay conditions, in erythrocytes from patients with primary hypertension is not
      critical for the development of moderate hypertension.

PMID- 9627145
TI  - Effect of 20 days' bed rest on the reverse cholesterol transport system in
      healthy young subjects.
AB  - OBJECTIVES: To study the effects of 20 days of bed rest on HDL cholesterol,
      lipoprotein lipase, hepatic triglyceride lipase, cholesterol ester transfer
      protein and lecithin-cholesterol acyltransferase. DESIGN: A 20-day intervention
      study. SETTING: Makita general hospital. SUBJECTS: Five male and five female
      healthy participants, mean age 20.4 years, range 19-24 years. INTERVENTIONS:
      Twenty days of bed rest. MAIN OUTCOME MEASURES: Lipid, lipoprotein, lipoprotein
      lipase, hepatic triglyceride lipase, cholesterol ester transfer protein and
      lecithin-cholesterol acyltransferase. RESULTS: Fasting HDL, HDL2 and HDL3
      cholesterol levels decreased from 1.748 to 1.404 mmol L(-1) (P < 0.01), from
      0.807 to 0.628 mmol L(-1) (P < 0.01) and from 0.939 to 0.784 mmol L(-1) (P <
      0.05), respectively, while VLDL triglyceride levels increased from 0.365 to 0.754
      mmol L(-1) (P < 0.05). Plasma post-heparin lipoprotein lipase activity decreased
      from 0.494 to 0.418 micromol mL(-1) h(-1) (P < 0.01), but plasma post-heparin
      hepatic triglyceride lipase activity and cholesterol ester transfer protein
      activity did not change during bed rest. Lecithin-cholesterol acyltransferase
      activity increased from 72.5 to 84.8 nmol mL(-1) h(-1) (P < 0.001). CONCLUSIONS:
      Twenty days of bed rest induced a decline in HDL cholesterol levels and an
      increase in VLDL triglyceride levels. When considering lipoprotein lipase,
      hepatic triglyceride lipase, cholesterol ester transfer protein and lecithin
      cholesterol acyltransferase as factors in the decreased HDL cholesterol, the
      contribution of lipoprotein lipase is suggested.

PMID- 9627146
TI  - Low molecular weight heparin-induced skin necrosis occurring distant from
      injection sites and without thrombocytopenia.
AB  - In this paper we report a case of 76-year-old white male patient with skin
      necrosis induced by subcutaneous prophylactic administration of low-molecular
      weight heparin (LMWH). Skin necrosis occurred distant from heparin injection
      sites and without concomitant thrombocytopenia. This is the first reported case
      presenting these clinical findings.

PMID- 9627147
TI  - Identification of homozygous lipoprotein lipase gene mutation in a woman with
      recurrent aggravation of hypertriglyceridaemia induced by pregnancy.
AB  - We herein report a case of a 40-year-old Japanese woman (patient IT) with a
      history of recurrent aggravation of hypertriglyceridaemia, pancreatitis and
      miscarriages in three previous pregnancies. However, strict dietary intervention
      was applied during a fourth pregnancy. As a result, acute pancreatitis was
      avoided, and the patient gave birth to a healthy infant. In patient IT, the
      underlying etiology of the recurrent aggravation of hypertriglyceridaemia during
      pregnancy was a lipoprotein lipase (LPL) gene aberration. She was homozygous for
      LPL deficiency due to a nonsense mutation (TGG1401 --> TGA/Trp382 --> Stop) in
      exon 8 of the LPL gene, which resulted in the absence of LPL activity and
      immunoreactive LPL mass. Our findings indicate that, in LPL deficiency, pregnancy
      seriously exacerbates hypertriglyceridaemia and increases the risk of acute
      pancreatitis, which endangers both the mother and fetus. Early diagnosis of LPL
      deficiency and appropriate management thereof are essential for normal
      childbirth.

PMID- 9627148
TI  - Cardiopathia fantastica exposed by rapid sequential serum creatine kinase
      analysis.
AB  - Rapid, sequential serum creatine kinase measurements may be used to exclude acute
      myocardial infarction in patients presenting with acute chest pain. Two cases of
      cardiopathia fantastica (the cardiac variant of Munchausen's syndrome) are
      described. Both patients presented with symptoms of acute myocardial infarction
      and had electrocardiographic changes consistent with this diagnosis. Both
      patients also had a raised serum creatine kinase level at the time of
      presentation but were unable to mimic the rise in serum creatine kinase
      associated with acute myocardial infarction. Munchausen's syndrome was suspected
      when both patients responded poorly to news that their enzyme results excluded
      acute myocardial infarction.

PMID- 9627150
TI  - Chlamydia pneumoniae.

PMID- 9627149
TI  - Congestive heart failure in old age.

PMID- 9627151
TI  - Unilateral breast oedema as a manifestation of congestive heart failure.

PMID- 9627152
TI  - Acute nutmeg intoxication.

PMID- 9627153
TI  - Rheumatoid pleural effusion with detectable level of interleukin-15.

PMID- 9627154
TI  - Pharmacological treatment of diabetic patients with cardiovascular complications.
AB  - Cardiovascular complications are frequently present in insulin-dependent (IDDM)
      and non-insulin dependent diabetes mellitus (NIDDM) patients and confer a very
      poor prognosis. In this overview we critically analyse the current literature
      with regard to the benefits and also the possible harms of the available
      pharmacological treatment strategies in these patients. To date, insulin is the
      only hypoglycaemic agent which has been proven both effective and safe in NIDDM
      patients with cardiovascular complications. Also, several trials indicate that
      treatment with oral hypoglycaemic agents may confer a substantial risk in such
      patients. Conventional antihypertensive treatment, including betablockers and
      diuretics, has been convincingly shown to reduce mortality and morbidity in
      diabetic nephropathy and in NIDDM patients. However, this may not be the case
      with newer antihypertensive agents, such as angiotensin-converting enzyme (ACE)
      inhibitors and calcium channel blockers. Likewise, convincing evidence is lacking
      that these newer antihypertensive agents provide meaningful clinical benefit when
      compared to the conventional treatment regarding slower progression of diabetic
      nephropathy or their impact on lipid and glucose metabolism. Cholesterol lowering
      therapy with statins and aspirin treatment have also been repeatedly shown to
      improve the prognosis of diabetic patients with coronary heart disease.

PMID- 9627155
TI  - Informing patients and relatives about do-not-resuscitate decisions. Attitudes of
      cardiologists and nurses in Sweden.
AB  - OBJECTIVES: To survey the attitudes of Swedish cardiologists and nurses regarding
      information given to patients and relatives concerning do-not-resuscitate (DNR)
      status. METHOD: Questionnaire. SETTING: Nationwide, 2 years after the publication
      of a proposal of guidelines on DNR. SUBJECTS: 10% random sample of members of the
      Swedish Cardiac Society, 104 physicians and 196 nurses. Response rate 73%.
      RESULTS: According to most Swedish cardiologists and cardiac nurses, patients and
      relatives should be honestly informed about a patient's DNR status if they ask
      for information. Almost all (97%) answered that the relatives of a noncompetent
      patient should be informed when they ask and (67%) believe that the relatives
      should be informed even if they do not ask. Most of the respondents (61%) stated
      that the patient, if mentally competent, should be informed about the DNR status
      first and decide if the information should be passed on to relatives. Only 12% of
      the respondents were of the opinion that if the relatives asked for this
      information to be withheld from the patient, this should be respected even if the
      patient asked for information, and 45% believed it should be respected if the
      patient did not ask. With reference to the latter, many (31%) were uncertain. The
      cardiologists and cardiac nurses expressed almost identical opinions in the
      matter of informing patients and relatives about DNR status. CONCLUSIONS: Current
      guidelines recommend honest answers to questions and that priority should be
      given to the autonomy of the patient. However the guidelines do not offer any
      assistance when no questions are asked. In such cases, there may be an ethical
      conflict between two requirements: respect for the person and do not harm. Many
      health care professionals believe that the information could, in some cases, harm
      the patient. This conflict can hardly be solved by referring to more basic
      ethical values. More training in informing patients and relatives about delicate
      matters is probably required, together with more knowledge about the wishes of
      very ill patients.

PMID- 9627156
TI  - Liposuction in Dercum's disease: impact on haemostatic factors associated with
      cardiovascular disease and insulin sensitivity.
AB  - OBJECTIVE: To study the impact of adipose tissue removal by liposuction on
      factors associated with increased risk of cardiovascular atherosclerotic disease
      within the coagulation and fibrinolytic system and glucose metabolism. DESIGN,
      SETTING AND SUBJECTS: Liposuction was performed in 53 patients with Dercum's
      disease. The levels of fibrinogen, von Willebrand factor antigen (VWF:Ag) and
      plasminogen activator inhibitor type 1 activity (PAI-1) were measured
      preoperatively, and 2 weeks, 4 weeks and 3 months postoperatively. In a subsample
      of 10 patients, insulin sensitivity was determined before and 2-4 weeks after
      surgery using the 2-h euglycaemic hyperinsulinaemic clamp technique. The study
      was performed as a single-centre study. MAIN OUTCOME MEASURE: Fibrinogen, PAI-1
      and VWF:Ag levels, and glucose uptake before and after removal of adipose tissue.
      RESULTS: Weight reduction was sustained throughout the follow-up period with a
      mean decrease from 90.7 to 86.6 kg (P < 0.0001). There was a slight increase in
      levels of coagulation factors 2 and 4 weeks postoperatively, probably in reaction
      to the surgical trauma. After 3 months the values had returned to preoperative
      levels except for PAI-1, which still showed a slight increase (P < 0.05). In the
      subsample of 10 patients, glucose uptake was improved (P < 0.05) from a short
      term perspective after surgery. CONCLUSION: Surgical removal of adipose tissue,
      without change in lifestyle, does not seem to improve the levels of coagulation
      and fibrinolytic factors associated with cardiovascular atherosclerotic disease,
      whereas glucose takeup may be facilitated and insulin sensitivity increases from
      a short-term perspective.

PMID- 9627157
TI  - HFE mutations in patients with hereditary haemochromatosis in Sweden.
AB  - OBJECTIVE: To determine the frequency of mutations (C282Y and H63D) in a newly
      identified gene HFE in patients with hereditary haemochromatosis (HH) in Sweden.
      DESIGN: Molecular genetic analyses of the HFE gene (polymerase chain reaction
      (PCR) followed by enzyme restriction) were performed in genomic DNA from
      unrelated patients with a clinical diagnosis of HH and in healthy subjects.
      SETTINGS: Patients with HH treated with phlebotomies at Karolinska Hospital and
      Huddinge Hospital were analyzed. SUBJECTS: Eighty-seven unrelated patients with
      HH and 117 healthy controls. RESULTS: It was found that the HFE C282Y mutation
      occurs in 94.2% of chromosomes from patients with HH. Eighty patients (92.0%)
      were homozygous for the C282Y mutation and one was heterozygous. Three patients
      were heterozygous for both C282Y and H63D mutations. One patient was homozygous
      and one was heterozygous for the H63D mutation. One patient carried normal
      alleles. In healthy controls, the C282Y mutation occurred in nine subjects
      (7.7%), all of which were heterozygous. The H63D mutation was found in 28 control
      subjects, one of which was homozygous. CONCLUSIONS: We found that the majority of
      patients with HH have the C282Y mutation in the HFE gene. The frequency of the
      H63D mutation was higher in controls than in patients with HH, although in
      chromosomes at risk the frequency of the H63D mutation was higher in patients.

PMID- 9627158
TI  - Sleep and cardiac symptoms amongst women aged 40-64 years.
AB  - OBJECTIVES: To determine whether the occurrence of cardiac symptoms is related to
      sleep disturbances. DESIGN: An epidemiological survey by means of a
      questionnaire. SETTING: The county of Jamtland in northern Sweden. SUBJECTS:
      Randomly selected women (6000) aged 40-64 years, with a similar number of women
      in each 5-year age group. A total of 3669 responded. MAIN OUTCOME MEASURES: Sleep
      disturbances and cardiac symptoms. RESULTS: In total, 81.9% of the women reported
      a good night's sleep. Amongst them, 0.4% stated that they were troubled by both
      spasmodic chest pain and a sensation of irregular heart beat, 0.8% spasmodic
      chest pain alone, 5.8% irregular heart beat and 93.0% neither of these
      conditions. The corresponding frequencies amongst the women who slept poorly were
      1.5, 1.8, 15.0 and 81.7%, respectively (P < 0.0001). Amongst the subjects with
      reported sleep complaints, there was an increase in heart symptoms, both in those
      with trouble falling asleep, frequent awakenings and difficulty in getting to
      sleep again, and in those who awoke too early in the morning. Spasmodic chest
      pain was 8.8 (1.9-40.3) times and irregular heart beat 7.7 (3.3-18.1) times more
      common in women with nightmares almost every night than in those who never
      experienced nightmares. Daytime sleepiness was also associated with increased
      heart symptoms. CONCLUSION: Poor sleep was associated with an increase in
      spasmodic chest pain and irregular heart beat.

PMID- 9627159
TI  - The importance of tubulointerstitial injury in the early phase of primary
      glomerular disease.
AB  - OBJECTIVES: As tubulointerstitial damage is regarded secondary to glomerular
      injury in primary glomerulopathies, we assessed lesions to renal
      tubulointerstitium in recently diagnosed primary glomerular diseases and
      evaluated their impact on progression of the disease during the first 2 years
      after diagnosis. DESIGN: A nonrandomized prospective study assessing
      tubulointerstitial morphometry at diagnosis, markers of tubular function within
      the next 6 months and progression of the disease (creatinine clearance) during 24
      months' follow-up. SETTING: Single tertiary referral centre. SUBJECTS: Forty-six
      patients with primary glomerular disease, the diagnostic oligobiopsy performed
      within 2 months of the onset of clinical symptoms. INTERVENTIONS: All patients
      were subjected to antiinflammatory/immunosuppressive treatment. MAIN OUTCOME
      MEASURES: Alterations in results of tubulointerstitial morphometry and tubular
      function tests, correlations between these variables and parameters of
      nephrosis/renal function, selection of the most accurate predictor of disease
      progression within 24 months after diagnostic biopsy. RESULTS: Function of
      proximal tubules, markedly deteriorated at the time of diagnosis, significantly
      improved 6 months later (urinary beta2-microglobulin: P < 0.0025), along with
      reduction in proteinuria (P < 0.00125). No appreciable alterations in function of
      distal tubules were noted. Morphometric indices revealing interstitial expansion
      and tubular atrophy significantly correlated with creatinine clearance at 6
      months (P = 0.032) and were the best predictors of deteriorating renal function
      at 24 months. Excretion of beta2-microglobulin at the time of diagnosis was the
      best marker for impairment of glomerular filtration 6 months later. CONCLUSIONS:
      Significant damage to cortical tubulointerstitium occurs concurrently with
      glomerular injury in primary glomerulopathies and may predict the clinical course
      of the disease already in its initial phase.

PMID- 9627160
TI  - Risk factor clustering in patients with hypertension and non-insulin-dependent
      diabetes mellitus. The Skaraborg Hypertension Project.
AB  - OBJECTIVES: To assess the coexistence of hypertension and diabetes, associations
      with cardiovascular risk factors and the achievement of current treatment goals.
      DESIGN: A community-based, cross-sectional, observational study. SETTING:
      Hypertension and diabetes outpatient clinics in primary health care, Skara,
      Sweden. SUBJECTS: All patients (n = 1116; 488 men, 628 women) who performed an
      annual follow-up from May 1992 to September 1993. MAIN OUTCOME MEASURES:
      Hypertension, non-insulin-dependent diabetes mellitus (NIDDM), blood pressure,
      fasting B-glucose, lipids, HbAlc, body mass index (BMI), waist hip ratio (WHR).
      RESULTS: Hypertension alone was found in 286 men and 430 women, hypertension and
      NIDDM combined in 102 men and 102 women, and NIDDM alone in 100 men and 96 women.
      Taking new cases into account, the proportion of hypertension among NIDDM
      patients was 57%, and the proportion of NIDDM among hypertensives was 26%. Men
      and women with both hypertension and NIDDM had a higher systolic blood pressure
      and women also had a higher diastolic blood pressure (men 168/88 mmHg, women
      165/86 mmHg) than those with hypertension alone (men 152/87 mmHg, women 156/82
      mmHg) (P < or = 0.001). Cardiovascular risk factors accumulated in patients with
      both hypertension and NIDDM (triglycerides, BMI and WHR). A diastolic blood
      pressure < or = 90 mmHg was achieved by 71% men and 84% women with hypertension.
      HbAlc < 7.5% was attained by 71% men and 70% women with NIDDM. CONCLUSIONS: A
      considerable coexistence of hypertension and NIDDM was demonstrated.
      Cardiovascular risk factors clustered in patients with both diseases and their
      blood pressure was less controlled. These patients thus comprised a clinically
      defined group at high risk. By current guidelines, control of hypertension and
      NIDDM seemed appropriate.

PMID- 9627161
TI  - The role of serum ferritin in the diagnosis of iron deficiency anaemia in
      patients with liver cirrhosis.
AB  - OBJECTIVES: To determine the diagnostic values of serum ferritin and other
      conventional laboratory tests in the diagnosis of iron deficiency anaemia in
      patients with liver cirrhosis. DESIGN: Cross-sectional study for diagnostic
      tests. SETTING: University hospital. SUBJECTS: Seventy-two consecutive patients
      with liver cirrhosis in whom the haemoglobin level was less than 13.0 g dL(-1)
      for men and 12.0 g dL(-1) for women. The diagnosis of liver cirrhosis was based
      on characteristic clinical and hepatic ultrasonographic findings. MAIN OUTCOME
      MEASURES: By using absence of bone marrow iron as the standard criterion, the
      diagnostic powers of mean corpuscular volume, transferrin saturation, serum
      ferritin and the presence of hypochromic red cells in the diagnosis of iron
      deficiency were compared by analysing the likelihood ratios, the area under the
      receiver operating curves (ROC) and the stepwise logistic regression associated
      with each test. RESULTS: Twenty-nine patients (40.3%) demonstrated no stainable
      iron in the bone marrow. The likelihood ratios, the area under the ROC and the
      stepwise logistic regression indicated that serum ferritin was the most powerful
      test predictive of iron deficiency. Other tests added little further diagnostic
      values. The likelihood ratios associated with the serum ferritin levels were as
      follows: <50 microg L(-1), 22.3; 51-200 microg L(-1), 1.5-1.8; 201-400 microg L(
      1), 1.0; >400 microg L(-1), <1. These results indicate that serum ferritin level
      <50 microg L(-1) depict a very high probability of iron deficiency anaemia (0.83
      0.99) irrespective of the patient's pre-test probability. CONCLUSION: Serum
      ferritin is the most powerful noninvasive test for the diagnosis of iron
      deficiency anaemia in patients with liver cirrhosis. It should be the primary
      test of choice in patients suspected of having the disease. When the level was
      less than 50 microg L(-1), iron supplement may be prescribed without
      necessitating bone marrow aspiration.

PMID- 9627162
TI  - Factors associated with pre-hospital and in-hospital delay time in acute
      myocardial infarction: a 6-year experience.
AB  - OBJECTIVES: To explore factors associated with delay time prior to hospital
      admission and in hospital amongst acute myocardial infarction (AMI) patients with
      particular emphasis on the delay time to the administration of thrombolytic
      therapy. METHODS: During a 6-year period we prospectively computerized pre
      hospital and in-hospital time intervals for AMI patients admitted to the coronary
      care unit (CCU) direct from the emergency department (ED) or via paramedics, at
      Sahlgrenska Hospital, Goteborg, Sweden. RESULTS: Pre-hospital delay: independent
      predictors of a prolonged delay were increased age (P = 0.0007), female sex (P =
      0.02) and a history of hypertension (P = 0.03). For AMI patients who received
      thrombolytic treatment and the only independent predictor of a prolonged delay
      was increased age (P = 0.005). In-hospital delay: for all AMI patients
      independent predictors of a prolonged delay were prolonged pre-hospital delay (P
      < 0.0001), increased age (P = 0.03) and a history of angina (P = 0.002),
      hypertension (P = 0.01) and diabetes (P = 0.01). For thrombolytic treated AMI
      patients independent predictors of a prolonged delay were prolonged pre-hospital
      delay (P < 0.0001), female sex (P = 0.02) and a history of diabetes (P = 0.02).
      CONCLUSION: Risk factors for both pre-hospital and hospital delay time could in
      AMI be defined although slightly different. Two factors appeared for both, i.e.
      increasing age and a history of hypertension.

PMID- 9627163
TI  - Clostridium difficile colitis associated with a 'triple' regimen, containing
      clarithromycin and metronidazole, to eradicate Helicobacter pylori.
AB  - We describe a 54-year-old man with Helicobacter pylori (+) duodenal ulcer who
      developed Clostridium difficile associated colitis, 5 days after commencing a
      'triple' regimen consisting of omeprazole 20 mg b.d., metronidazole 500 mg b.d.
      and clarithromycin 500 mg b.d., to eradicate H. pylori. Despite the fact that
      oral metronidazole did not prevent the disease, the patient did well after
      treatment with oral metronidazole plus a yeast preparation (Saccharomyces
      bulardii). No relapse occurred.

PMID- 9627164
TI  - Lethal pulmonary hypertension in a young woman caused by unrecognized
      haemangiosis carcinomatosa.
AB  - A 38-year-old female is described, who was admitted with increasing respiratory
      distress, cough and visible blood stasis in the jugular veins. The most likely
      diagnosis in this young women taking oral contraceptives was pulmonary embolism,
      however, a ventilation-perfusion lung scan was normal. Echocardiography showed a
      dilated right ventricle and increased systolic pulmonary pressure. Despite
      administration of oxygen and intravenous heparin the patient died in circulatory
      collapse before further investigations could be initiated. Post-mortem
      examination revealed diffuse adenocarcinoma of the stomach (linitis plastica)
      with metastasis to local lymphnodes, lymphangiosis carcinomatosa of the liver,
      pancreas and spleen and tumour cell masses within the lumen of small pulmonary
      arteries leading to variable occlusions of the vessels. Fibrocellular intimal
      proliferation was found, leading to further obstruction and increased resistance
      to flow through the pulmonary vascular bed and to subacute cor pulmonale.

PMID- 9627165
TI  - Molecular mechanisms of sepsis.
AB  - Today a great number of problems in the field of bacterial sepsis remain to be
      solved. Understanding the molecular mechanisms of one of the most important
      bacterial products in the pathogenesis of sepsis - endotoxin may contribute to
      innovative and more effective therapies. Therefore, this review focuses on the
      structural and functional elements of endotoxin, its interaction with immune
      cells, and its biological activity. Finally, other bacterial components and their
      impact on sepsis are discussed.

PMID- 9627166
TI  - Clinical relevance of sepsis scores.
AB  - In this article sepsis scoring systems commonly used are presented as regards
      their results and shortcomings. Furthermore, in a more general context, the
      direct and indirect effect on the individual patients is discussed and
      recommendations are given on how to use scoring systems.

PMID- 9627167
TI  - Scope and limitations of antimicrobial therapy of sepsis in surgery.
AB  - OBJECTIVE: The goal of antibiotic therapy for surgical sepsis is to kill bacteria
      that intermittently or continuously reach the bloodstream from the residue of an
      operatively treated focus. While sepsis and conditions leading to sepsis
      compromise the immune system, antibiotics may become a fundamental determinant of
      the host's defense. No data from sound prospective randomized clinical antibiotic
      trials dealing with sepsis are available. Therefore we tested the hypothesis that
      treatment recommendations can be based on pharmacodynamics comparing in vitro
      activity of commonly used antimicrobials with concentrations sustained in vivo to
      provide for full coverage for bacteria of concern. RESULTS: The application of
      strict criteria for antibiotic choice to avoid selection of primary resistant
      strains reveals that most commonly used antibiotics render insufficient activity
      to eliminate pathogens that commonly cause surgical sepsis. Antibiotics that
      sustain in vivo concentration exceeding fourfold the MIC100 (highest minimal
      inhibitory concentration for all (100%) species tested) of Escherichia coli, for
      example, are 400 mg ciprofloxacin IV (MIC100 of 1224 strains=0.06 mg/dl, in vivo
      concentration=1 mg/dl for 12 h), and 1000 mg imipenem/cilastatin (MIC100 of 3142
      strains=0.14 mg/dl, in vivo concentration=2 mg/dl for 6 h). The third choice is
      one of the fourth- or, less convincingly, third-generation cephalosporins.
      Similar data for most pathogens causing sepsis are provided. First- and second
      generation cephalosporins and penicillin beta-lactamase inhibitor combinations
      generally do not achieve sufficient concentrations to cover the most important
      pathogens of sepsis. CONCLUSION: Sepsis is defined as a whole body's inflammatory
      response that is characterized by systemic signs and symptoms secondary to a
      focal infection. While many antibiotic trials have dealt with a focal infection,
      no prospective randomized antibiotic trial has dealt with sepsis per se.
      Antibiotic trials on focal infections generally exclude patients when their focal
      infection has progressed to sepsis. To circumvent the lack of controlled clinical
      trials we show that pharmacodynamics may provide sound foundation for antibiotic
      choice for sepsis.

PMID- 9627168
TI  - Thirty years of anti-mediator treatment in sepsis and septic shock--what have we
      learned?
AB  - Sepsis, the systemic response (specific and non-specific) of the body to an
      infection, is an increasing clinical problem. During the last 30 years, nearly 50
      clinical trials involving more than 10,000 patients have failed to demonstrate
      improvement of patients' outcome with different "anti-mediator" strategies. The
      wrong conceptional approaches to interact with the complex mediator network and
      flaws in study design and conduct are the main reasons for this disappointing
      situation. We learned, however, that the systemic host response is more than
      persistent uncontrolled inflammation; it is also a stimulation of the counter
      regulatory network. Although it is important to analyse the complex picture, we
      have now reached a point where more sophisticated strategies for describing
      complexity and novel attempts for synthesis are needed. Along this line, improved
      study designs (decrease of "signal-to-noise ratio") are mandatory. In addition,
      secondary preventive strategies are emphasised.

PMID- 9627169
TI  - Management of abdominal sepsis.
AB  - INTRODUCTION: Today the management of the different forms of peritonitis is
      generally standardised. The classification of primary and secondary peritonitis
      is well accepted. From a pathophysiological point of view, postoperative and post
      traumatic peritonitis should be considered as independent entities. The
      bacteriological isolates from the inflamed peritoneal cavity do not correlate
      with the clinical course, and the occurrence of enterococci and bacteroides may
      be slightly related to ongoing infectious complications. CLASSIFICATION: Valuable
      scoring systems mainly rely on systemic signs of the septic disease and seem to
      better differentiate the prognosis of the disease than more surgically oriented
      scores do. Although the scoring systems did not allow any clinical decision, they
      should be used to help better compare patients treated in different institutions.
      The observation of the minor relevance of bacteriology and the superiority of
      general sepsis scores agrees with the fact that pre-existing septic organ
      dysfunction and pre-existing comorbidity are the main determinants of mortality.
      TREATMENT: Surgical therapy focuses on the control of the source of infection
      because it has been clearly shown that, without resolving the source of
      infection, the prognosis remains poor. Adjuvant surgical measures aim at the
      further reduction of the bacterial load in the peritoneal cavity. Planned
      relaparotomy, relaparotomy on demand, and continuous closed peritoneal lavage are
      used. RESULTS: Clinical results proved these methods to be equally effective
      although pathophysiological considerations favour closed peritoneal lavage.
      CONCLUSION: Summarising the available data, we need a more sophisticated
      understanding of the pathophysiology of the peritonitis, and well-designed
      clinical studies are necessary to define the optimal surgical treatment
      modalities.

PMID- 9627170
TI  - Outcome of patients with sepsis and septic shock after ICU treatment.
AB  - OBJECTIVE: Today, sepsis syndrome is the leading cause of death in adult, non
      coronary intensive care units (ICUs) and is of great clinical importance. The
      purpose of this review was to evaluate recent prospective studies concerning the
      short- and long-term prognosis of patients suffering from systemic inflammatory
      response syndrome (SIRS), sepsis, severe sepsis and septic shock. It has been
      shown in multicentre prospective surveys that 1% and 0.3% of all patients
      admitted to hospitals suffer, respectively, from bacteraemia alone and
      bacteraemia with severe sepsis. This rate increases, of course, when only
      admissions to the ICUs are considered: the above-mentioned rates increase then by
      a factor of 8 and 30, respectively. Thus, approximately 10% of patients in the
      ICU suffer from sepsis, 6% from severe sepsis and 2-3% from septic shock. SIRS
      occurs more frequently and its occurrence ranges from 40% to 70% of all patients
      admitted to ICUs. Thereby, 40-70% suffering from SIRS progress to a more severe
      septic-disease state. The overall prognosis is still poor, despite the recent
      advances in ICU treatment. The mortality rate of SIRS ranges from 6% to 7% and in
      septic shock amounts to over 50%. In particular, abdominal sepsis exhibits the
      highest mortality rate with 72%. The long-term prognosis is equally poor; only
      approximately 30% survived the first year after hospital admission. CONCLUSION:
      The prognosis of sepsis and septic shock remains poor, despite the advances in
      ICU treatment. Although prognostic factors have been identified for some
      patients, groups have not yet been able to identify the immediate or long-term
      prognosis for the majority of these septic patients.

PMID- 9627171
TI  - Laparoscopic versus conventional colorectal resection: a prospective randomised
      study of postoperative ileus and early postoperative feeding.
AB  - BACKGROUND: A shorter duration of postoperative ileus and earlier oral
      alimentation of patients may be a clinically relevant benefit of laparoscopic
      compared with conventional colorectal resection. PATIENTS/METHODS: A total of 60
      patients were randomised to either laparoscopic (n=30) or conventional (n=30)
      resection of colorectal tumours. Major endpoints were the postoperative time to
      the first bowel movement and the time until oral feeding without parenteral
      alimentation was tolerated. Minor endpoints were the postoperative interval to
      the first peristalsis and first passage of flatus, the distribution of radio
      opaque markers in abdominal radiographs on day 3 and day 5 and the incidence of
      postoperative vomiting. RESULTS: Age, gender. ASA-classification and type of
      resection were comparable in the two groups. Peristalsis was first noticed 26+/-9
      h after laparoscopic and 38+/-17 h after conventional colorectal resection
      (P<0.01). First flatus occurred 50+/-19 h after laparoscopic and 79+/-21 h after
      conventional surgery (P<0.01). The incidence of postoperative vomiting was
      similar in both groups. Three days after surgery radio-opaque markers were found
      more often in the right colon (P<0.01) and less often in the small intestine
      (P<0.05) in laparoscopic compared with conventional patients. Five days after
      laparoscopic surgery, more markers had reached the left colon (P<0.05). The first
      bowel movement occurred 70+/-32 h after laparoscopic and 91+/-22 h after
      conventional resection (P<0.01). Oral feeding without additional parenteral
      alimentation was tolerated 3.3+/-0.7 days after laparoscopic and 5.0+/-1.5 days
      after conventional surgery (P<0.01). CONCLUSION: The shorter duration of
      postoperative ileus allows earlier restoration of oral feeding after laparoscopic
      compared with conventional colorectal resection and therefore increases quality
      of life immediately after resection of colorectal tumours.

PMID- 9627172
TI  - Cystic tumours of the pancreas: diagnostic accuracy, pathologic observations and
      surgical consequences.
AB  - BACKGROUND: Cystic neoplasms of the pancreas account for only 1% of primary
      pancreatic lesions. However, patients with these tumors are diagnosed more
      frequently. Up to now, nonsurgical management is still the established form of
      treatment of benign cystic tumours of the pancreas. METHODS: Between 1987 and
      1996 we treated 51 patients with serous and mucinous cystadenoma and their
      malignant counterparts, serous and mucinous cystadenocarcinoma. RESULTS: Eighty
      five percent of the patients presented symptoms. Computed tomography and
      endoscopic cholangiopancreatography (ERCP) were the most sensitive diagnostic
      techniques; however, in three patients with serous cystadenoma and in one patient
      with serous cystadenocarcinoma, ERCP findings were completely normal. The tumour
      was resected in all but one patient. There was no perioperative mortality. After
      dismissal from the hospital, all patients in whom benign tumours had been
      resected are still alive; however, the late mortality of mucinous
      cystadenocarcinoma was 36% after a median follow-up of 6 years. CONCLUSION:
      Surgical resection is recommended in all cystic tumours, even in serous cystic
      tumours, because symptoms may develop and malignant transformation to serous
      cystadenocarcinoma is possible.

PMID- 9627173
TI  - Treatment of liver metastases in patients with neuroendocrine tumors.
AB  - BACKGROUND: Hepatic metastases of neuroendocrine tumors demand differentiated
      therapeutic management due to the unique natural course and hormone secretion of
      the tumors. AIM: The purpose of the prospective nonrandomized study was to review
      the institutional experience with surgical treatment of hepatic neuroendocrine
      metastases. PATIENTS AND METHODS: From September 1992 until March 1996 29
      consecutive patients with neuroendocrine tumors have been evaluated for surgical
      treatment of liver metastases. Of them, 11 (37.9%) fulfilled criteria for
      surgical treatment of hepatic secondary tumors. Extensive preoperative workup was
      carried out. Patients were divided in groups for curative or palliative
      resection. Liver transplantation was carried out in selected patients with
      disseminated liver metastases. RESULTS: Of 29 patients 4 (13.7%) underwent
      curative resection and in 3 patients (10.3%) palliative resection was performed.
      The patients who underwent curative resection are all biochemically and
      clinically tumor free at a mean postoperative follow-up of 22.3 months. Two
      patients who underwent palliative resection are alive at 40 and 29 months,
      respectively. From 12 patients evaluated for liver transplantation 4 were
      considered as suitable candidates. CONCLUSIONS: Liver resection can be
      recommended in patients with hepatic metastases of neuroendocrine tumors in terms
      of potential survival prolongation and palliation. Liver transplantation is
      generally acceptable treatment in highly selected group of these patients. Long
      term results have to be awaited before definitive proof of the beneficial effect
      of surgical treatment.

PMID- 9627174
TI  - Reduced TNFalpha and IL-6 production in patients who mount a preoperative acute
      phase response.
AB  - BACKGROUND/AIMS: In some patients postoperative infective complications are
      related to a reduced resistance to the operative trauma and the perioperative
      microbiological challenge. To investigate preoperative alterations in the immune
      responses in patients who had mounted an acute-phase response before the
      operation, we measured the capacity of tumor necrosis factor alpha and
      interleukin-6 production in whole blood. PATIENTS/METHODS: Serum concentrations
      of C-reactive protein, alpha1-antitrypsin, albumin, and prealbumin were measured
      in 89 patients submitted for major abdominal surgery on their admission to
      hospital. RESULTS: In 23 patients (26%) we found concentrations of at least one,
      and in 16 patients (18%) of two or more of these variables beyond the reference
      range. Patients who mounted an acute-phase response released 37% less TNFalpha
      (1339 vs. 848 pg/ml) and 31% less IL-6 (24293 vs. 16900 pg/ml) when whole blood
      was stimulated with lipopolysaccharide 0.5 microg/ml. CONCLUSION: Patients who
      mount an acute-phase response before operation may thus have a downregulated
      immune response at the level of proinflammatory cytokines. This is likely to
      alter their resistance to invasive micro-organisms in the perioperative period.

PMID- 9627175
TI  - Failure of Kupffer cell blockade to prevent disseminated intravascular
      coagulation in endotoxemic rats despite improved survival.
AB  - OBJECTIVE: Studies were conducted to evaluate the impact of gadolinium chloride
      (GdCl3), an agent which blocks the phagocytosis of liver macrophages (Kupffer
      cells, KC), on the coagulation system and on mortality in a model of rats
      subjected to a lethal dose of Escherichia coli lipopolysaccharide (LPS) (10 mg/kg
      body weight, intravenously). METHODS: Rats were either pretreated with GdCl3 (10
      mg/kg, i.v., 48 h and 24 h prior to LPS exposure) or saline vehicle. A variety of
      coagulation parameters such as activated partial prothrombin time (aPTT),
      fibrinogen, systemic platelet count, antithrombin III (AT III), and activities of
      factors V, VII, and XII were monitored in the early (1 h) and late time course
      (16 h) following administration of E.coli LPS. RESULTS: The administration of LPS
      resulted in the development of disseminated intravascular coagulation (DIC) and
      was associated with a mortality rate of 47% within 16 h. Blockade of KC by GdCl3
      completely abolished LPS-related mortality (0%). However, despite improved
      survival, GdCl3 failed to prevent laboratory and clinical signs of DIC. GdCl3 per
      se even contributed to coagulatory and fibrinolytic disorders. CONCLUSION: These
      results confirm reports on the protective potential of GdCl3 pretreatment in
      experimental endotoxemia. However, the present study does not support the concept
      of DIC as a strong prognostic criterion for the outcome of sepsis and septic
      shock. Furthermore, the results presented suggest a minor role for KC in LPS
      mediated activation of coagulation and indicate an involvement of KC in LPS
      associated lethality independent of the coagulation system.

PMID- 9627176
TI  - De novo expression of the cell adhesion molecule E-selectin on gastric cancer
      endothelium.
AB  - BACKGROUND AND AIMS: Angiogenesis and the molecular phenotype of the tumor
      vasculature determine tumor growth and metastasis. PATIENTS/METHODS: In a series
      of 58 gastric cancer patients, vascular density and the antigenic profile of
      endothelial cells in normal, inflamed and malignant gastric tissues were compared
      using immunohistochemistry. RESULTS: In both benign gastric mucosa and primary
      gastric cancer vascular density was inflammation-independent. However, increased
      vascularity in primary tumors was positively associated with a high tumor cell
      density suggesting tumor-induced angiogenesis (P=0.00001 ). P-selectin was
      expressed in most of the gastric mucosa samples on a small fraction of vessels
      and increased in the presence of moderate to strong leukocyte infiltrate. VCAM-1
      positive mucosal vessels were rare and showed no association with inflammation. E
      selectin and the EN 7/44 antigen defining budding vessels were absent on normal
      and inflamed endothelium. In contrast, in primary gastric cancer de novo
      expression of both E-selectin and the EN 7/44 antigen was observed. E-selectin
      positive vessels were preferentially found in vascular-rich tumor areas
      (P=0.0043) independently of leukocyte infiltration. Upregulation of VCAM-1 on
      tumor-associated endothelium was closely related to inflammation (P=0.019), while
      P-selectin expression resembled that in benign mucosa. CONCLUSIONS:
      Differentially expressed vascular molecules may influence the functional
      characteristics of extravasating leukocytes and represent new targets in anti
      gastric cancer therapy.

PMID- 9627177
TI  - Role of HLA antigens in liver transplantation with special reference to cellular
      immune reactions.
AB  - In previous statistical analyses we have demonstrated the importance of the
      dualistic effect of HLA on liver transplant survival: HLA compatibility decreases
      cellular rejection but also increases other immunologically mediated, HLA
      restricted mechanisms of allograft injury. More recently these results have been
      confirmed by other researchers, and several studies have shown higher recurrence
      rates of infectious diseases such as hepatitis B and C and CMV hepatitis for HLA
      compatible liver transplants. Although current practice does not consider HLA in
      liver transplantation, cellular in vitro studies show a significant role of HLA
      antigens in clinically relevant phenomena. While increasing the amount of
      infection-related immune damage, HLA compatibility also decreases the
      alloproliferative response of the recipient to the donor tissue. Further studies
      must examine whether non-HLA antigens such as tissue-specific antigens and heat
      shock-proteins participate in this process, and how target cells can present
      different peptides such as soluble HLA antigens or viral proteins to the
      recipient.

PMID- 9627178
TI  - The impact of donor organ quality on postoperative liver function after
      orthotopic rat liver transplantation.
AB  - The impact of donor factors for posttransplant liver function was evaluated in
      the model of orthotopic rearterialized liver transplantation in the rat. The
      effect of donor fasting, parenteral hyperalimentation, hypotension, warm ischemia
      and endotoxins on histology, clinical chemistry and MEGX test was analyzed in
      syngeneic and allogeneic recipients of livers stored for 4 hrs on ice. In
      syngeneic animals, 20 min of warm ischemia led to significantly elevated serum
      transaminase levels and degree 2 histological damage on POD 2. Endotoxins
      produced a grade 1 histological damage. All groups had a lower MEGX formation
      rate compared to controls. In allogeneic animals, warm ischemia was the single
      most detrimental parameter. The strength of the rejection response on POD 8 did
      not depend on the type of donor pretreatment. The major finding of this non
      survival study is the deleterious effect of warm ischemia and endotoxin on the
      functional and structural integrity of liver grafts after 4 hrs of cold ischemia.

PMID- 9627179
TI  - Significance of retinoblastoma and mdm2 gene expression as prognostic markers for
      soft-tissue sarcoma.
AB  - The growth regulatory function of the retinoblastoma protein (RB) can be
      suppressed by mdm2 via RB/mdm2 interaction by perturbation of the RB suppression
      of the E2F function. The goal of this study was to examine the clinical value of
      immunohistochemical (IHC) RB detection and its relationship to mdm2
      overexpression in a cohort of 198 adult primary soft-tissue sarcomas (STS). RB
      overexpression reveals, multivariately, a correlation with survival (RR=1.59,
      P=0.037) as well as mdm2 positivity (RR=2.32, P=0.0035). Stratification of RB
      results to mdm2 staining shows a prognostic graduation in four levels. Patients
      with positivity for both antibodies have the highest risk (RR=3.30, P=0.002) and
      the poorest prognosis (projected 5-year survival rate, 18.6%); those with
      negativity for both antibodies show the most favourable prognosis (projected 5
      year survival rate, 63.4%). Intermediately, an isolated RB overexpression
      (projected 5-year survival rate, 46.1%) is more favourable than an isolated mdm2
      positivity (projected 5-year survival rate, 33.5%). To sum up, this study proves
      that RB and mdm2 overexpression have an individual and also an additive effect on
      prognosis in STS.

PMID- 9627180
TI  - Motion evoked brain potentials parallel the consistency of coherent motion
      perception in humans.
AB  - The perception of global coherent motion perception in complex motion patterns
      containing different direction vectors was investigated. Random dot kinematograms
      (RDK), plaids and fragmented plaid pattern were presented in which direction
      vectors of the moving elements were varied. In order to elicit coherent motion
      perception, all elements were displaced in the same direction (delta0 degrees).
      In a second condition, fifty percent of the elements were moved diagonally
      downwards to the left, with the remaining elements moving orthogonally (delta 90
      degrees). Simultaneously with psychophysical judgements on the perceived motion
      direction, visual evoked potentials (VEPs) were recorded at occipital electrode
      positions. Onset of a global coherent motion was associated with a VEP negativity
      occurring at about 200 ms. The amplitude of this component was clearly reduced
      when local ambiguous signals could not be integrated to produce the perception of
      global coherent motion.

PMID- 9627181
TI  - Regionally specific neuronal expression of human APOE gene in transgenic mice.
AB  - Apolipoprotein E (APOE, gene; apoE, protein) is a susceptibility gene for late
      onset Alzheimer's disease (AD). To examine whether neurons can synthesize apoE,
      we performed in situ hybridization on brain tissue of transgenic mice carrying
      genomic constructs for the three major human APOE alleles. We find human APOE
      mRNA in glial cells of cerebellum, striatum and cerebral cortex and also in
      neurons of cerebral cortex, corresponding to apoE localization in humans.
      Synthesis of apoE by neurons implies that models of AD may need to consider
      intrinsic apoE production in addition to uptake. Inclusion of human regulatory
      sequences may result in more realistic transgenic models of human disease.

PMID- 9627182
TI  - Nefiracetam elevates extracellular acetylcholine level in the frontal cortex of
      rats with cerebral cholinergic dysfunctions: an in vivo microdialysis study.
AB  - We determined the effect of nefiracetam, a novel cognitive enhancer, on the
      extracellular acetylcholine (ACh) level in the frontal cortex of freely moving
      rats, using a microdialysis technique without an acetylcholinesterase inhibitor
      in the perfusate. Treatment with nefiracetam (10 mg/kg, p.o.) produced a
      significant increase in the level of ACh in the brain dialysate, compared with
      the vehicle-treated group. This enhancing effect was also observed when the ACh
      level was elevated by administration of scopolamine (1 mg/kg, i.p.) at 45 min
      after the treatment with nefiracetam. In addition, perfusion of nefiracetam at
      the concentration of 10 microM significantly increased the extracellular ACh
      level in the frontal cortex of basal forebrain (BF)-lesioned rats, in which a
      marked decrease of the basal ACh level was observed in this region. These results
      suggest that enhancement of cortical ACh release by nefiracetam may contribute to
      an anti-amnesic effect on the learning deficits induced by treatment of
      scopolamine or BF-lesion in rats.

PMID- 9627183
TI  - Uterine inflammation as a noxious visceral stimulus: behavioral characterization
      in the rat.
AB  - We have developed a model of uterine inflammation in the rat. The purpose of this
      study was to characterize the behavioral manifestations of uterine pain. Mustard
      oil was injected into one uterine horn to produce chemical inflammation. Control
      rats were sham-operated. Non-stop videotape recording was performed for 7 days to
      monitor rat behavior. Rats with uterine inflammation showed abnormal behavior
      during the first 4 days (hunching, hump-backed position, licking of the lower
      abdomen, repeated waves of contraction of the ipsilateral oblique musculature
      with inward turning of the ipsilateral hindlimb, stretching, squashing of the
      lower abdomen against the floor) suggestive of visceral pain and evidence of
      flank muscle hyperalgesia over 7 days indicative of referred visceral pain. This
      model resembles closely a state of inflammatory uterine pain and will allow to
      gain further insight into the neural processes which contribute to visceral
      nociception.

PMID- 9627184
TI  - In situ identification of neuronal nitric oxide synthase (NOS-I) mRNA in mouse
      and rat skeletal muscle.
AB  - Skeletal muscle provides a major source of the signaling molecule nitric oxide
      (NO) however in situ identification of NO-synthase (NOS) mRNA has not been
      verified. We have used NOS-I (neuronal NOS) probes prepared from plasmid DNA by
      reverse transcription-polymerase chain reaction (RT-PCR) to detect mRNA
      transcripts in skeletal muscle cells and myofibers of rat and mouse. Mouse C2C12
      myoblasts and myotubes reveal strong cytosolic in situ hybridization (ISH)
      signals in vitro. In adult animals, ISH signals are detectable in striated
      myofibers at subsarcolemmal and perinuclear regions whilst the myofibrillar
      compartment is devoid of signals. Expression of NOS-I mRNA in fusion-competent
      myoblasts suggests that the NOS/NO system is of relevance to myogenic
      differentiation. Compartmentalization of NOS-I mRNA may reflect spatiofunctional
      actions between NOS message and protein and the putative subcellular NO targets.

PMID- 9627185
TI  - Microtubule-associated protein 1a is involved in the early development of the rat
      spinal cord.
AB  - The expression of microtubule-associated protein 1a (MAP1a) in the developing rat
      spinal cord was studied using the monoclonal antibody BW6. Immunoblots of
      microtubule preparations revealed the presence of MAP1a in spinal cord tissue of
      rats aged embryonal day 16 and postnatal day 0. The spinal cord matrix layer,
      between embryonal days 12-17, displayed a pattern of MAP1a-positive processes,
      horizontally oriented in between the membrane limitans interna and externa. The
      mantle layer stained intensely for MAP1a between embryonal day 12 and postnatal
      day 2. MAP1a was found in neuronal cell bodies, axons and dendrites, located
      mainly in the ventral and intermediate mantle layer. In the marginal layer, MAP1a
      positive axons could be observed between embryonal days 14-18. During further
      development, the intensity of the MAP1a staining in the spinal columns gradually
      decreased. These expression patterns indicate an involvement of MAP1a in the
      proliferation and differentiation of neuroblasts, and the maturation of the long
      spinal fiber systems, i.e. early events in spinal cord development

PMID- 9627186
TI  - Medical amygdala-induced spike potentiation in the rat dentate gyrus is dependent
      on N-methyl-D-aspartate receptors and subcortical afferents.
AB  - We have previously found that high-frequency stimulation of the medial amygdala
      (MeA) produces a long-lasting potentiation of the population spike at medial
      perforant path-granule cell synapses in the dentate gyrus of anesthetized rats.
      The present study was performed to determine whether this novel form of
      potentiation requires activation of N-methyl-D-aspartate (NMDA) receptors and
      subcortical afferents. The MeA-induced spike potentiation was completely blocked
      by the NMDA receptor antagonist 3-((R,S)-2-carboxypiperazin-4-yl)-propyl-1
      phosphonic acid (3.5 mg/kg, i.p). When the fimbria-fornix, a major pathway of
      subcortical afferents, was lesioned, the early phase of MeA-induced spike
      potentiation remained intact, but the late phase of potentiation was abolished.
      These results suggest that the NMDA receptor is essentially required for the
      induction of MeA-induced spike potentiation, while subcortical afferents
      contribute to the establishment of potentiation.

PMID- 9627187
TI  - Unbiased number of vestibular ganglion neurons in the mouse.
AB  - Vestibular sensory information from the labyrinth and otolith organs is conducted
      to the central nervous system exclusively via primary vestibular afferents (PVA)
      originating from neurons located in the vestibular ganglion (VG). In the present
      study, the total number of VG neurons was determined in two different wild-type
      mouse strains using the principles of unbiased stereological counting methods by
      means of the physical disector. 3316 (+/-225 SD) neurons were present in the VG
      of the B6CBA-strain and 3551 (+/-239 SD) in C57BL/6J-mice. Since no statistical
      difference was detected between the two strains, the pooled mean number was 3433
      (+/-232 SD) neurons. This is the first unbiased estimate of VG neurons aimed at
      providing a numerical basis for comparative studies and for the impact of
      experimental, pharmacological and pathological conditions as well as ageing on
      the survival and maintenance of VG neurons.

PMID- 9627188
TI  - Retinoic acid reduces staurosporine-induced apoptotic damage in chick embryonic
      neurons by suppressing reactive oxygen species production.
AB  - The effect of all-trans retinoic acid (RA), which is known as a regulator of cell
      growth and differentiation, was studied during neuronal apoptosis. Apoptosis was
      induced in primary cultures of chick embryonic neurons by treatment with
      staurosporine (200 nM) for 24 h which led to a reduction of cellular viability to
      40% compared to 83% in untreated cultures as well as to an increase in the number
      of apoptotic neurons (determined by nuclear staining with Hoechst 33258) to 60%
      compared to 15% in untreated cultures. RA (1 nM-10 microM) reduced the number of
      non-viable and apoptotic cells in a concentration-dependent manner and the
      maximal response was seen at 1 microM RA with 60% cellular viability and 38%
      apoptotic neurons. The production of mitochondrial reactive oxygen species (ROS,
      determined by the fluorescent indicator dihydrorhodamine) was elevated 4.4-fold
      after 4 h of staurosporine-treatment which was reduced to a 2-fold increase in
      the presence of 10 microM RA. The results indicate that RA was able to reduce
      apoptotic damage in staurosporine-treated chick embryonic neurons by suppressing
      the production of ROS.

PMID- 9627189
TI  - Modulation of upper extremity motoneurone excitability following noxious finger
      tip stimulation in man: a study with transcranial magnetic stimulation.
AB  - Little is known about nociceptive reflex mechanisms in the upper limb in humans.
      To investigate nociceptive effects on spinal motoneurone excitability, a
      conditioning noxious stimulus was applied to the index finger of five healthy
      subjects. Motor evoked potentials (MEPs) following contralateral transcranial
      magnetic stimulation (TMS) were recorded from thenar eminence (TE) and biceps
      brachii (BB) muscles ipsilateral to finger stimulation. TMS was randomly applied
      alone or combined with preceding finger stimulation at an interstimulus interval
      of 100 ms. MEP amplitudes were profoundly suppressed in TE and augmented in BB.
      We conclude that nociception produces a differential effect on different spinal
      motoneurone pools, which may be part of a complex protective reflex mechanism in
      the upper limb of humans.

PMID- 9627190
TI  - Blockade of brain type II interleukin-1 receptors potentiates IL1beta-induced
      anorexia in mice.
AB  - Interleukin-1beta (IL1beta) peripheral activities are mediated by type I IL1
      receptors (IL1RI), whereas type II IL1 receptors (IL1RII) act as 'decoy' targets.
      To study the functionality of IL1RII in the brain, mice were treated with an
      intracerebroventricular injection of a neutralising MoAb directed against IL1RII
      (4E2, 1 microg) followed by recombinant rat IL1beta at a dose (2 ng) that
      produced a moderate but significant decrease of food intake 1 h 30 min after
      injection. The administration of 4E2 to IL-1beta treated mice significantly
      potentiated IL1beta-induced decrease in food intake without altering hypothermia.
      The effects of IL1beta were abrogated in the positive control group treated with
      IL1ra (2 microg, i.c.v). These results suggest that brain IL1RII down-regulate
      the effects of IL1beta on its cell targets in the brain.

PMID- 9627191
TI  - Effect of butanedione monoxime on the contractility of guinea pig ileum and on
      the electrophysiological activity of myenteric S-type neurones.
AB  - 2,3-Butanedione monoxime (BDM) has demonstrated protective effects on isolated
      cardiac tissues, and on smooth muscle but its mechanism of action is not fully
      understood. To simultaneously study the effect of BDM on muscle contractility and
      on neuronal activity, the effect of BDM was tested in the contractile force of
      myenteric plexus-longitudinal muscle strips and in electrophysiological activity
      of myenteric S-type neurones of guinea pig ileum. BDM reduces, in a dose
      dependent manner, the force of the spontaneous motility and the contractions
      induced by acetylcholine, bethanechol and electrical stimulation. The same BDM
      concentrations depolarize the neuronal membrane and reduce the rate of evoked
      firing. The effect of BDM can be attributed to a direct effect on the smooth
      muscle and to modifications of the neuronal activity.

PMID- 9627192
TI  - Potentiation of adenosine 5'-triphosphate calcium responses by diadenosine
      pentaphosphate in individual rat cerebellar astrocytes.
AB  - The calcium responses induced by adenosine 5'-triphosphate (ATP) were examined in
      single cerebellar type 1 astrocytes by fura-2 microfluorometry. ATP elicited fast
      and transient increases of intracellular calcium concentration ([Ca2+]i) even in
      the absence of extracellular calcium, indicating the involvement of metabotropic
      purinoceptors. The co-stimulation with P1P5-di(adenosine-5')pentaphosphate (Ap5A;
      0.1 microM) potentiated ATP-metabotropic calcium responses. After this
      preincubation ineffective concentrations of ATP triggered 40% of maximal
      response. Co-stimulation with Ap5A and ATP was mandatory. The potentiated
      response to ATP was also independent of extracellular Ca2+ and was maintained for
      long periods of time (h). These results show a relevant interaction of
      purinoceptors that may imply a novel mechanism of action for diadenosine
      polyphosphates.

PMID- 9627193
TI  - Influences of the bed nucleus of the stria terminalis and of the paraventricular
      nucleus of the hypothalamus on the excitability of hippocampal-lateral septal
      synapses in mice.
AB  - Previous experiments have shown that conditioning in aversive situations is
      associated with specific changes in excitability of hippocampal-septal synaptic
      transmission and that these changes might be related to a modulation of this
      synaptic transmission by afferents originating from the bed nucleus of the stria
      terminalis (BNST) and from the paraventricular nucleus (PVN) of the hypothalamus.
      Accordingly, the aim of the present experiment was to assess changes in
      excitability of hippocampal-septal synapses by varying the interval between the
      application of a conditioning pulse in either the BNST or the PVN, and a test
      pulse in fimbria fibers (FF). Electrical stimulation of FF, induces in the
      lateral septum (LS) a field potential characterized by two negative waves (N2 and
      N3) the magnitude of which is an index of excitability of two populations of
      target cells located in the ventral and dorsal lateral septum, respectively.
      Results showed that prestimulation of both the BNST and the PVN produced an
      increase in the amplitude of the N3 wave, although the optimal interpulse
      interval required for producing maximal increase was different as a function of
      the two structures. Only prestimulation of the BNST induced a significant
      increase in the amplitude of the N2 wave. These results suggest that the PVN
      projects mainly to the dorsal aspect of the LS, while the BNST projects to both
      dorsal and ventral parts of the LS. Together with results from previous
      experiments conducted in behaving mice exposed to conditioned aversive stimuli,
      it is concluded that these projections might play a role in the relief of
      contextual conditioned fear.

PMID- 9627194
TI  - Supraspinal involvement in the production of mechanical allodynia by spinal nerve
      injury in rats.
AB  - This study examined whether or not the production of mechanical allodynia in a
      rat model of neuropathic pain required an involvement of supraspinal site(s). To
      this aim, we assessed the effect of spinal cord section at the L1 segment level
      on the mechanical allodynia sign (i.e. tail flick/twitch response), which was
      elicited by innocuous von Frey hair stimulation of the tail after unilateral
      transection of the tail-innervating nerve superior caudal trunk (SCT) at the
      level between the S3 and S4 spinal nerves. Cord transection or hemisection of the
      cord ipsilateral to the injured SCT drastically (though not completely) blocked
      the behavioral sign of mechanical allodynia (leaving noxious pinprick-elicited
      tail withdrawal reflex intact), whereas sham section or contralateral hemisection
      of the cord was without effect. These results suggest that the generation of
      mechanical allodynia following partial peripheral nerve injury involves
      transmission of the triggering sensory signal to a site(s) rostral to the L1
      segment via an ipsilateral pathway(s).

PMID- 9627195
TI  - In vitro changes in capacitative Ca2+ entry in neuroblastoma X glioma NG108-15
      cells.
AB  - Changes in capacitative Ca2+ entry were studied in neuroblastoma x glioma NG108
      15 cells with fura-2 fluorescence measurements in the following three culture
      conditions. The application of thapsigargin (250 nM) with a Ca2+-free solution
      depleted intracellular Ca2+ stores and the capacitative Ca2+ entry was induced by
      the addition of extracellular Ca2+ in the cells cultured in the medium for
      proliferation. The capacitative Ca2+ entry decreased in the cells cultured in the
      medium for neuronal differentiation. When these cells resumed proliferation after
      changing the culture media to the initial medium for proliferation, the
      capacitative Ca2+ entry increased again and exceeded the level in the initial
      proliferation state. These results suggested that the capacitative Ca2+ entry
      occurred more intensely at the proliferation state than at the neuronally
      differentiated state.

PMID- 9627196
TI  - Serum prolactin levels are elevated also after pseudo-epileptic seizures.
AB  - The aim of the study was to evaluate the sensitivity, specificity and the
      predictive values of repeated serum prolactin measurements in relation to
      epileptic seizures versus pseudoseizures. The method used was prospective
      measuring of serum prolactin from blood samples drawn (1) 15 min after seizure
      and (2) 2 hr after the first sample. Two parameters were used: the absolute
      maximal level; and the relative rise in blood level. In the study 38 had epilepsy
      (simple or complex partial seizures with or without secondary generalisation);
      and 20 had pseudo-epileptic seizures. In all cases, the diagnoses were made
      independent of the prolactin levels. In 30/38 (79%) of epilepsy patients and
      17/20 (85%) of pseudoseizure patients, the diagnoses were corroborated by
      intensive EEG monitoring (video or cassette telemetry). There was a statistically
      significant rise in prolactin levels in both groups (p < 0.0001 and < 0.02,
      respectively), and also a significant difference between the two groups. However,
      repeated measurements in a number of patients (epilepsy: mean 1.5 measurements;
      pseudo; mean 2.1) showed also considerable intra-patient variations. The
      sensitivity for the maximal rise in pseudoseizures (5.5x) was only 20% and the
      negative predictive value 40%. For the cut-off in absolute level (1025
      microU/ml), the corresponding figures were 34% and 44%, respectively. The rather
      limited discriminative power of prolactin measurements makes it of questionable
      value in discerning between epileptic and pseudo-epileptic seizures.

PMID- 9627197
TI  - Electrophysiologic assessment of autonomic function in epilepsy.
AB  - Sudden unexpected death associated with epilepsy (SUDEP) is an important clinical
      problem. Peri-ictal autonomic dysfunction is thought to play a role in SUDEP and
      few means exist for clinical identification of patients at risk. Sympathetic
      function was assessed by measuring sympathetic skin responses (SSR) elicited in
      the hand by auditory or tactile stimulation or by inspiration. Parasympathetic
      function was assessed by recording the R-R interval (RRI) and determining its
      variability in subsequent heartbeats. Fifty epilepsy patients had significantly
      greater SSR amplitudes and latencies than controls. The RRI was shorter in
      patients than in controls and the mean successive difference (MSD) was less, but
      significance was not reached. Twenty patients at possible risk for SUDEP (male,
      generalized seizures, intermittent medication noncompliance, drug and alcohol
      abuse, traumatic or structural aetiology) differed significantly from controls in
      SSR and RRI. Epilepsy patients may differ in autonomic function from the general
      population, and these differences may be relevant to SUDEP. The SSR and the RRI
      may be a simple means of assessing autonomic function in epilepsy outpatients.

PMID- 9627198
TI  - Photosensitivity--better informing patients with epilepsy of their individual
      risk.
AB  - Photosensitive epilepsy is relatively rare. However, a large proportion of
      individuals with epilepsy perceive that they are at an increased risk of a
      seizure whilst exposed to specific photic material. The difference between
      perceived and real risk may be due to inadequate education and misinformation.
      One half of the participants in the present survey could not recall being
      informed of the result of the 'gold standard' test for photosensitivity-
      intermittent photic stimulation during an electroencephalogram. Furthermore,
      approximately one-third of our sample were apparently given inaccurate and
      overcautious advice about their everyday exposure to photic material. Better
      information and advice is crucial to improve this situation in the future. The
      majority of people with epilepsy (>95%) who are not photosensitive can pursue
      activities that involve flickering or patterned light, encompassing educational,
      employment and leisure opportunities, without undue concern.

PMID- 9627199
TI  - Fear of seizures: an investigation and treatment.
AB  - Despite the wealth of epidemiological evidence showing the comorbidity of
      epilepsy with various forms of psychopathology, there has been little systematic
      investigation of its relationship with affective disorders. This study aims to
      explore the phenomenon of seizure fear. Survey data have suggested that patients
      commonly fear death and/or brain damage as a result of their seizures, but
      documented cases of seizure phobia are rare and infrequently address issues of
      treatment. The study describes the exploration and successful cognitive
      behavioural treatment of a case of seizure phobia in a 26 year old woman with a 9
      year history of epilepsy following a subarachnoid haemorrhage. The findings
      represent an important development in the much-neglected study of seizure fear.
      The case highlights some of the factors which may contribute to the genesis and
      maintenance of epilepsy-related psychopathologies and consequently has important
      implications for theoretical modelling in this area. Furthermore, it provides
      encouraging evidence to support the use of cognitive-behavioural techniques in
      treatment of these disorders.

PMID- 9627200
TI  - Seizure recurrence and risk factors after withdrawal of chronic antiepileptic
      therapy in children.
AB  - The aim of this study was to identify the risk factors for seizure recurrence
      after withdrawal of chronic antiepileptic therapy in 226 children: 136 with
      partial epilepsies and 90 with generalized epilepsies. The influence on prognosis
      of the different variables was assessed retrospectively with univariate and
      multivariate analysis. With a mean observation period of 5.85+/-3.87 years,
      seizure recurrence occurred in 24.3% of all patients with partial and generalized
      epilepsies. In children with partial epilepsies, the following factors were found
      to significantly increase relapse risk after treatment withdrawal: neurological
      abnormalities; interval between seizures less than 1 month at onset of illness;
      the use of VPA in treating seizures; start of withdrawal after 6 years of age;
      frontal paroxysmal activity; and abnormal EEG before drug withdrawal. In children
      with generalized epilepsies the risk factors were found to be: abnormal neonatal
      period; first seizure after 10 years of age; mean duration of seizures greater
      than 1 minute; poor school progress and generalized spike-waves in EEG. The
      factors associated with the risk of recurrence in children with generalized
      epilepsy appear to differ from to those related to partial epilepsies, in which
      seizure treatment with VPA was associated with an increased recurrence risk after
      the withdrawal of antiepileptic drugs.

PMID- 9627201
TI  - Neuroimaging of children with partial seizures.
AB  - The predictive value of abnormal neurological findings on neuroimaging (NI) of
      children with partial seizures (PS) was studied. The sample comprised 143
      children and adolescents with PS from 1979 to 1996. Fifty patients had the
      following abnormal NI findings: diffuse atrophy and porencephalic cyst (5.6%
      each), hemiatrophy, tumors, neurocutaneous syndrome brain lesions, and dysgenesis
      (4.2% each), and arachnoid cyst and hydrocephalus (2.1% each). There were
      significantly more NI abnormalities among those with simple PS than among the
      other groups of complex PS or PS with secondary generalization. All cases of
      porencephalic cyst (n = 8), and hemiatrophy (n = 6) were in the hemiparetic
      group, all cases of tumor (n = 6) were in the normal group, while most cases of
      diffuse atrophy were in the mentally retarded group. Patients with abnormal NIs
      had a significantly earlier age of seizure onset than the others. The chance of
      finding a treatable abnormality in neuroimaging was 5% for tumors and 2% for
      arachnoid cysts in the group of patients with PS and normal neurological
      findings. Neither an abnormality detected in a neurological examination nor the
      type of seizure are predictive parameters for suggesting the presence of a
      resectable brain tumor. All patients with newly diagnosed PS should undergo an
      MRI.

PMID- 9627202
TI  - Economic analysis of epilepsy treatment: a cost minimization analysis comparing
      carbamazepine and lamotrigine in the UK.
AB  - New anti-epileptic drugs differ from existing standard therapies not in their
      clinical efficacy, but in their side-effects profiles. To determine the relative
      economic value of these agents, one must compare drug costs, costs of resources
      employed in the management of adverse events, and costs associated with
      therapeutic switching. In this economic analysis, carbamazepine (CBZ) and
      lamotrigine (LTG) are evaluated in monotherapy treatment of partial and/or
      general tonic-clonic seizures in the UK. Adverse event and tolerability data are
      obtained from a published randomized controlled trial of CBZ vs. LTG. A Delphi
      panel of clinicians advised treatment patterns for adverse events. Cost data are
      obtained from public sources. Results show that CBZ therapy costs about one-third
      of LTG therapy (pound sterling 179 for CBZ vs. pound sterling 522 for LTG) even
      after the costs associated with the management of adverse events and therapeutic
      switching are considered.

PMID- 9627203
TI  - Prescribing of anti-epileptic drugs in the northern and Yorkshire region: 1992
      1995.
AB  - Epilepsy is a condition for which regular drug treatment is normally prescribed.
      We have examined the primary care prescribing rates for anti-epileptic drugs
      (AEDs) in a region of northern England with a population of 6.8 million. Over the
      4-year period 1992-1995 the number of AED prescription items issued rose by 15%.
      A third of this rise is accounted for by increased prescribing of the new
      anticonvulsants, vigabatrin, lamotrigine and gabapentin, which are primarily
      indicated for adjunct use. Prescribing of phenytoin and barbiturates fell over
      the same period, but this reduction was more than compensated for by increased
      prescribing of carbamazepine and sodium valproate. There were notable differences
      in both the overall volume and the choice of AEDs used in different health
      authority areas and these are probably attributable to the influence of the local
      secondary-care sector on the therapeutic regimens adopted by general
      practitioners in the area.

PMID- 9627204
TI  - Knowledge, attitudes and practice of epilepsy: experience at a comprehensive
      rural health services project.
AB  - Beliefs regarding cause and preference of the treatment modality are important
      factors influencing any epilepsy programme. Patients own attitudes towards the on
      going treatment are equally important in ensuring success of any such programme.
      The study involved interviews of 80 patients with epilepsy attending a
      comprehensive rural health services project, and was conducted according to a
      structured questionnaire. The majority of the patients were well informed
      regarding the cause of epilepsy, but more than half had tried alternative
      treatment methods. Many patients had misconceptions regarding the goal of the
      treatment and the consequences of missing a prescribed drug dose. Surprisingly
      few patients avoided taking medicines on days of religious fast. It was also
      noted that most patients depended on free medical supplies from the clinic
      dispensary, and a small number of patients would stop the medicines if these were
      not given free of cost. We stress the need to understand patients' concepts about
      the cause and the treatment of epilepsy, the need to educate them and their
      families regarding principles of modern medical treatment of epilepsy and most
      importantly, the need to maintain a regular, uninterrupted supply of free
      medicines, to improve the effectiveness of similar epilepsy management programmes
      in the setting of rural India and other developing countries.

PMID- 9627205
TI  - Epilepsies among twins born in families of Indian probands with epilepsy.
AB  - Twins have a high frequency of adverse perinatal events and have been reported to
      have an increased risk of seizures. Contrary to popular belief, a recent study
      reported that twins do not have an increased risk of seizures. We studied the
      relationship of twinning and epilepsy in India. The frequency of twinning in
      families of probands with epilepsy was compared with the frequency of twinning
      among hospital births in the same region of India. We also compared consecutively
      ascertained probands with epilepsy for their twin status and the occurrence of
      epilepsies in their twin and non-twin relatives. The frequency of twin births in
      families of 524 probands with epilepsy was comparable to the twin births among
      consecutive deliveries over a 3-year period in another government hospital in the
      same catchment area (1:99 vs. 1:75). Every 1 in 58 of probands with epilepsy was
      a twin while a twin was born in these families every 1 in 71 live births. The
      frequency of epilepsy in non-proband twin relatives was 1.5% compared with 2%
      among non-proband, non-twin relatives. This data suggests that twin birth is not
      a major risk factor for seizures even in families of Indian probands with
      epilepsy. Family data such as ours can be used to study the contribution by
      genetic factors in the pathogenesis of complex genetic diseases such as human
      epilepsies.

PMID- 9627206
TI  - Automatic detection of epileptiform spikes in the electrocorticogram: a
      comparison of two algorithms.
AB  - The detection and analysis of epileptiform spikes is of major importance for the
      presurgical evaluation of epilepsy patients concerning the localization of the
      epileptogenic zone. To examine the reliability of automatic spike detection
      software for intracranial subdural strip and intrahippocampal depth recordings,
      the results of two algorithms were compared with those of two human reviewers.
      The first is a newly developed two-stage algorithm whose first stage uses the
      enhanced prediction error of an updating linear predictor of the
      electrocorticogram (ECoG) to select candidates for the following mimetic rule
      based system. The second system is the well-known rule-based algorithm developed
      by Gotman. Both systems achieved only a surprisingly small number of common
      detections (32 and 24%) accompanied by a high number of false detections (65 and
      78%). Though the results were better for the first system, the clinical use of
      the automatic spike detection systems should be limited to the following
      purposes. 1. To achieve data reduction before visual inspection of the spike
      candidates. 2. To get an overview of the spatial distribution of spike counts. 3.
      To obtain a data basis for the analysis of quantitative spike parameters.

PMID- 9627207
TI  - Clinical characteristics, seizure spread patterns and prognosis of seizures
      associated with a single small cerebral calcific CT lesion.
AB  - Clinical characteristics of 97 patients with epilepsy associated with a small
      single cerebral calcific CT lesion (SSCCCTL), measuring 20 mm or less were
      analysed. The mean age was 20 years and 60% were in the first and second decades.
      Eighteen (18.5%) patients had a previous history of unprovoked seizures, with
      complex partial seizures (61%) being the most common type. Seizures could be
      localized to a single ILAE site in 73% of patients. None had neurological deficit
      and electroencephalograph abnormalities were noted in 29% of patients. Fifty-one
      (53%) patients had breakthrough seizures and were more common with frontal
      location. By 7 years 71.5% (95% confidence intervals (CI) 53.7-85.4) of patients
      achieved 3-year remission and 66% (CI 32.4-88.2) had achieved 5-year remission.
      The clinical pattern of the seizures was clearly distinctive to allow it to be
      localized to the location of the lesion on computerized tomography (CT) scan in
      25 (26%) patients and in another 31 (31%) patients nearer to the anatomical site
      of the lesion on the CT scan. There was discordance between clinical localization
      and CT location of the lesion in 15 patients. Nine of the 10 patients with
      occipital or parieto-occipital location had focal tonic-clonic seizures with
      secondary generalization. Both patients with temporal location had motor
      seizures. The relevance of these findings to the seizure propagation was
      discussed.

PMID- 9627208
TI  - Cognitive effects of anticonvulsant monotherapy in elderly patients: a placebo
      controlled study.
AB  - Old age is recognized to be the commonest time in life to develop epilepsy. There
      is a perception that older patients are more sensitive to the deleterious
      cognitive effects of antiepileptic drugs (AEDs). Elderly patients (median age 70
      years, range 60-88 years) taking anticonvulsant monotherapy (10 carbamazepine
      [CBZ], 8 sodium valproate [VPA], 5 phenytoin [PHT]) took an extra dose of their
      usual medication (200mg CBZ, 500mg VPA, 100mg PHT) and matched placebo each for a
      month in random order. The concentrations of AEDs were higher after 7 and 28 days
      of active treatment compared with placebo (7 days: CBZ 9.5 vs. 7.8 mg L(-1), p <
      0.05; VPA 97 vs. 64 mg L(-1), p < 0.05; PHT 13 vs. 11 mg L(-1), p < 0.05; 28
      days: CBZ 9.4 vs. 7.7 mg L(-1); p < 0.01, VPA 85 vs. 60 mg L(-1), p < 0.05; PHT
      16 vs. 13 mg L(-1), p < 0.05). Despite these increases in concentration, there
      were no significant changes in attention, reaction time, finger tapping, memory,
      side-effect scale or sedation scoring during the active phases compared with
      placebo phases for the three drugs analysed together and separately. Elderly
      patients taking standard AEDs as monotherapy did not develop cognitive impairment
      when the dose was modestly increased within the target range for each drug.

PMID- 9627209
TI  - Lamotrigine toxicity secondary to sertraline.
AB  - Blood level monitoring helps to determine the therapeutic and toxic ranges for
      anticonvulsants and antidepressants. We investigated initial drug-drug
      interactions between lamotrigine and sertraline. We report on case histories of
      two epileptic patients who were initially on lamotrigine and to whom sertraline
      was added to control psychiatric features. In case 1, a total daily dose of 25 mg
      sertraline, with nondetectable sertraline and desmethylsertraline blood levels,
      resulted in a doubling of the lamotrigine blood level with symptoms of toxicity.
      In case 2, a 25 mg reduction in the total daily dose of sertraline resulted in
      halving of the lamotrigine blood level even though the lamotrigine dosage was
      increased by 33%. This shows that sertraline has potent interactions with
      lamotrigine metabolism. The authors hypothesize that inhibition of
      glucuronidation is responsible. Clinicians are advised to observe for symptoms of
      toxicity and to do serial blood levels to monitor this interaction.

PMID- 9627210
TI  - Hypothalamic hamartomas causing gelastic epilepsy: two cases and a review of the
      literature.
AB  - Two cases of hypothalamic hamartomas causing gelastic epilepsy are described. The
      clinical presentations and the radiological features are presented, and the
      mechanisms involved in laughing attacks are discussed. The literature is reviewed
      and it is suggested the complete extirpation of the hamartomas is the treatment
      of choice in gelastic epilepsy.

PMID- 9627211
TI  - Effect of autotransplantation of microvessel fragments on experimental random
      pattern flaps in the rat.
AB  - We examined whether autotransplantation of microvessel fragments (Mvf) and/or
      myofibroblasts (Mf) into an in vivo skin flap model might improve the survival of
      the ischemic flap. If so, this could improve blood perfusion, increase blood
      flow, and improve the survival of the flap. A skin flap was raised on the back of
      each rat (n = 15 in each group). In the control group, the flap was sutured to
      the original bed. In the other groups (1) phosphate-buffered saline; (2)
      autotransplanted Mvf, Mf, or Mvf plus Mf, and (3) a homogenized mixture of Mvf
      plus Mf was injected into the distal part of the flap. In a further group, Mvf
      labeled with DiI-acetylated low-density lipoprotein were autotransplanted with Mf
      into the distal part of the flap, and India ink was perfused through the
      abdominal aorta 7 days postoperatively. The transplanted Mvf plus Mf group showed
      better flap survival after 7 days than the other groups (p < 0.02). Labeling with
      DiI-acetylated low-density lipoprotein showed that transplanted Mvf sent
      arborizations into the nearby tissue. India ink was found in the lumina within
      such arborizations. Thus, autotransplanted Mvf may improve the survival of
      ischemic skin flaps by promoting the early formation of patent connections
      between Mvf and the host's microcirculatory system. This apparently requires the
      presence of Mf.

PMID- 9627212
TI  - Protection of xeno-hepatocytes from complement-mediated cytolysis by transduction
      with homologous restriction factor 20 gene using retroviral vector.
AB  - Xeno-hepatocyte transplantation has the possibility to substitute for clinical
      liver transplantation in certain restricted hepatic diseases such as inherited
      metabolic disorders. To overcome human complement-dependent cytotoxicity on xeno
      hepatocytes, the effectiveness of ex vivo transfer with the homologous
      restriction factor 20 (HRF20, CD59) gene was examined on primary-cultured xeno
      hepatocytes using a retroviral vector. Primary-cultured rat hepatocytes
      transduced with HRF20 cDNA expressed HRF20 antigen by flow cytometric analysis
      and showed the integration of HRF20 cDNA to the genomic DNA by the polymerase
      chain reaction. The viability of rat hepatocytes incubated with 50% human serum
      was decreased due to complement-dependent cytotoxicity, whereas that of the
      transfectant was significantly protected (77.2+/-9.4 vs. 97.8+/-5.2%, p < 0.01).
      It was concluded that primary-cultured xeno-hepatocytes transduced with HRF20
      cDNA using a retroviral vector could escape complement-dependent cytolysis by
      human serum.

PMID- 9627213
TI  - Bone morphogenetic protein in bone neoplasms: comparison of different detection
      methods.
AB  - The presence of bone morphogenetic proteins (BMPs) in 13 primary bone neoplasms
      was investigated with conventional bioassay method and immunohistochemically
      using antiserum against highly purified mixture of bovine BMPs as antibody. In
      conventional bioassay after implantation of lyophilized bone tumor tissues into
      mouse muscle pouches 9/13 samples turned out positive by radiography and 10/13
      histologically. By immunohistochemical staining, using the avidin-biotin
      peroxidase method, signs of BMPs could be verified in all cases investigated.
      Microscopical scoring showed the local concentration of BMPs to be especially
      high in sections from giant cell tumors when compared to other bone neoplasms.

PMID- 9627214
TI  - Exogenous L-arginine protects liver microcirculation from ischemia reperfusion
      injury.
AB  - Hepatic ischemia followed by reperfusion evokes an imbalance between the
      vasoregulatory compounds endothelin and nitric oxide (NO) followed by
      constriction of the vascular bed, leading to microcirculatory disturbances and
      reduced blood flow, thereby causing hypoxia and liver damage. The aim of this
      study was to protect the liver microcirculation by maintaining this delicate
      balance. MATERIAL AND METHODS: In an in vivo ischemia/reperfusion model with
      portal decompression by a splenocaval shunt, hepatic ischemia was induced for 30
      min by Pringle's maneuver. The effect of the NO donor L-arginine (400 mg/kg b.w.
      i.v.) was assessed by in vivo microscopy. Microhemodynamic studies, including the
      sinusoidal perfusion rate, diameters of hepatic sinusoids and postsinusoidal
      venules, leukocyte endothelium interactions and leukocyte velocity were
      performed. Microcirculatory data were compared with local tissue pO2 and serum
      transaminase levels. RESULTS: After ischemia the diameters of sinusoids and
      postsinusoidal venules were significantly reduced to 76+/-7 and 86+/-10%
      respectively in the nontreatment group, but dilated to 102+/-3 and 105+/-7% in
      the group treated with L-arginine (p < 0.001). The percentage of permanently
      adherent leukocytes in sinusoids and venules was increased by ischemia, but L
      arginine reversed this increase (p < 0.001). Perfusion rate was improved to 90+/
      2 compared with 83+/-5% in the untreated group (p < 0.01). Systemic arterial
      blood pressure was not affected by administration of the NO donor. The
      postischemic increase in serum transaminase levels was diminished in the
      treatment group (ASAT: p < 0.05). Local postischemic hepatic tissue pO2 was
      significantly decreased to 45% of basal values after 30 min and to 55% after 60
      min of reperfusion (p < 0.05). Administration of L-arginine results in a
      significant increase in local tissue pO2 to 86 and 106% of basal values
      respectively (p < 0.05). CONCLUSION: These data indicate that L-arginine improves
      hepatic microcirculation after warm ischemia by increasing sinusoidal perfusion
      rate and by diminishing leukocyte endothelium interactions. Maintained integrity
      of microcirculation is associated with sufficient oxygen supply and improved
      hepatocellular function.

PMID- 9627215
TI  - Influence of intermittent ischemia on thioacetamide-induced rat liver cirrhosis.
AB  - We studied the influence of intermittent ischemic injury on thioacetamide-induced
      liver cirrhosis in rats. Wistar rats were divided into group A, intermittent
      ischemic injury to liver cirrhosis, and group B, continuous ischemic injury to
      liver cirrhosis. Total ischemic time was 60 min in both groups. In group A,
      ischemic injury consisted of a repetition 4 times of 15 min ischemia and 5 min
      reperfusion. The ATP level of the liver was measured before ischemia, before
      reperfusion, and 60 min after reperfusion. Bile was collected to determine bile
      flow rate. The ATP level in the liver tissue 60 min after reperfusion was
      significantly (p < 0.05) higher in group A than in group B. The ATP level
      immediately before reperfusion was also significantly (p < 0.05) higher in group
      A than in group B. The survival rate 1 week after ischemic injury and bile flow
      rate 60 min after reperfusion were significantly (p < 0.01) higher in group A
      compared with those in group B. The energy level was much higher in intermittent
      ischemic injury than in continuous ischemic injury immediately before reperfusion
      and after reperfusion. Survival rate and bile flow rate were higher in
      intermittent ischemic injury than in continuous ischemic injury. Therefore it
      suggests that the viability of the liver was maintained better in intermittent
      ischemic injury than in continuous ischemic injury.

PMID- 9627216
TI  - Beneficial effects of verapamil on intestinal ischemia and reperfusion injury:
      pretreatment versus postischemic treatment.
AB  - We studied the effect of verapamil on intestinal ischemia and reperfusion (I/R)
      injury. Intestinal ischemia was induced by clamping the superior mesenteric
      artery for 30 min followed by reperfusion. Magnetic resonance spectroscopy was
      employed as a marker of the changes in the energy metabolism. Further,
      histological changes and the changes of water contents were evaluated. Recovery
      rates of energy metabolism after intestinal I/R were improved by verapamil,
      administered before and after ischemia, and tissue edema was significantly
      reduced with verapamil. These findings suggest that verapamil results in an
      improved recovery of the energy metabolism and cellular preservation, presumably
      by reducing the intracellular calcium influx.

PMID- 9627217
TI  - Surgical trauma evokes a rise in the frequency of hematopoietic progenitor cells
      and cytokine levels in blood circulation.
AB  - Alterations in the mononuclear cell populations in the blood circulation are
      among the most characteristic changes after surgical trauma. They reflect changes
      in the hematopoietic compartment which develop following surgery. The process of
      mobilization and differentiation of the hematopoietic population is regulated by
      cytokines known as growth factors for stem and progenitor cells (SCF, IL-1, IL-3,
      IL-6, IL-1L, TNF, CSFs). Our question was whether operative trauma resulted in
      the release of the hematopoietic progenitor cells to the blood circulation and an
      increase in the blood level of cytokines participating in hematopoiesis. The
      studies were carried out in patients with chronic cholelithiasis, undergoing
      elective open cholecystectomy under general anesthesia. An increase in the
      frequency of circulating CD34+ hematopoietic progenitor cells was seen between
      days 3 and 7 after surgery. Moreover, a significant increase in the percentage of
      immature cells of myeloid lineage (CD13+, CD14+, CD33+) was seen on the 1st and
      3rd postoperative days. This could be the result of an expansion of the total
      bone marrow cell number after surgery and a subsequent release of these cells
      into the blood circulation. The changes in blood cell populations were
      accompanied by an increase in IL-6 on days 1, 3, and 7 following surgery, in IL
      6sR on days 10 and 14 and in IL-8 on days 1 and 3. No significant changes in IL
      1alpha, IL-1beta, IL-3 and IL-11 were noted. A small rise in GM-CSF was noted in
      few patients on the 3rd and 7th postoperative days. It is known that IL6 is
      involved in hematopoiesis, that the IL6-IL-6sR complex may induce both
      proliferation and differentiation of hematopoietic progenitor cells and that IL8
      possesses progenitor cell mobilization properties. The appearance of
      hematopoietic progenitor cells in the blood following surgery may represent a
      process for the expansion of the immune cell pool after trauma and maintaining of
      the reserves at a certain level.

PMID- 9627218
TI  - Myocardial hemodynamic and metabolic changes during abdominal insufflation with
      carbon dioxide.
AB  - It is a well-known fact that laparoscopic procedures performed with carbon
      dioxide insufflation impair myocardial function. In this study, we aimed to
      determine the safety limitations of various intra-abdominal pressure values
      during abdominal insufflation with carbon dioxide. Of the 24 mongrel dogs, 6 were
      assigned to one of four different pressure groups (10, 15, 20 and 30 mm Hg),
      respectively. Cardiac output, right/left heart pressures, and the first
      derivative of ventricular pressure were monitored. Myocardial oxygen consumption,
      myocardial lactate/oxygen extraction, tissue lactate and adenosine triphosphate
      levels were determined. Measurements were performed initially as a control, at 15
      min intervals during 1 h of insufflation and 1 h after desufflation. At 10 mm Hg
      carbon dioxide pressure, hemodynamic and metabolic parameters were not
      significantly different. Cardiac output decreased significantly in the 20 and 30
      mm Hg groups (p < 0.05: 10, 15 vs. 20, 30 mm Hg). Although cardiac output did not
      change at 15 mm Hg, the dp/dt value was significantly reduced. Cardiac output at
      the 60th min was 1,960+/-75 ml/min in the 10 mm Hg group, 1,885+/-40 ml/min in
      the 15 mm Hg group, 1,770+/-45 ml/min in the 20 mm Hg group and 1,695+/-40 ml/min
      in the 30 mm Hg group. Myocardial oxygen consumption was reduced at 15, 20 and 30
      mm Hg (p < 0.05: 10 vs. 15, 20 and 30 mm Hg). In the myocardial tissue, ATP
      decreased from 19+/-2 to 12+/-1.2 micromol/g at 15 mm Hg, from 19+/-1.9 to 9.4+/
      1.3 micromol/g at 20 mm Hg and from 18+/-3.2 to 8.2+/-1.9 micromol/g at 30 mm Hg.
      Changes in hemodynamic and metabolic parameters of the heart are reversible and
      may not lead to any significant impairments in patients having normal
      cardiopulmonary function, but pose a risk in patients with respiratory disease
      and limited myocardial reserve.

PMID- 9627219
TI  - Histone H3 phosphorylation and expression of cyclins A and B1 measured in
      individual cells during their progression through G2 and mitosis.
AB  - Phosphorylation of histone H3 (H3) on Ser-10 correlates with chromatin
      condensation at mitosis. A new monoclonal antibody (anti-H3-P) was developed that
      recognizes phosphorylated H3 (H3-P). This antibody was used in multiparameter
      flow cytometric analysis to relate H3 phosphorylation in individual human
      leukemic cells to the cells' position in the cycle as well as their expression of
      cyclins A and B1. Mitotic cells, from prophase to telophase, reacted with anti-H3
      P; the binding of the antibody to chromatin of interphase cells was several times
      weaker. Cell growth in the presence of staurosporine, an inhibitor of the
      kinase(s) that phosphorylate H3, abolished the cells' reactivity with the
      antibody. The reactivity also was abolished by incubation of permeabilized
      mitotic cells with alkaline phosphatase. These data indicate that, within
      permeabilized cells, the antibody is indeed specific for H3-P and does not detect
      the unphosphorylated epitope. All cells reacting with anti-H3-P, with the
      exception of prophase and early prometaphase, were cyclin A negative; the
      expression of cyclin B1 in these cells was threefold higher than in G2 cells. The
      analysis of phosphorylation of H3 in individual cells when combined with
      multiparameter analysis of their cycle position and expression of other proteins
      offers new possibilities to study molecular mechanisms associated with the G2 to
      M transition and chromatin condensation. It also offers an assay to screen in
      vivo inhibitors of kinase(s) or phosphatase(s) involved in H3 phosphorylation or
      dephosphorylation, and it provides a valuable marker to identify mitotic cells by
      cytometry.

PMID- 9627220
TI  - Bivariate flow cytometric analysis of DNA content versus immunopositivity for
      ribonucleotide reductase M1 subunit in the cell cycle.
AB  - Ribonucleotide reductase (RR) is a cytoplasmatic enzyme catalyzing the reduction
      of all four ribonucleotides to their corresponding deoxyribonucleotides. Its
      activity strongly correlates to the rate of DNA synthesis. By using a specific
      monoclonal antibody against the large M1 subunit of RR, we assessed the
      expression of M1-RR versus DNA content by dual-parameter flow cytometry. The aim
      of this paper was to compare the variations in the immunopositivity for M1-RR
      during the cell cycle to the positivity for other cell cycle markers identifying
      either proliferating cells (Ki-67 and PCNA) or quiescent cells (statin). To do
      this, normal human embryonic fibroblasts in different growth conditions as well
      as several other mammalian cell lines (rat C6 glioma cells; mouse 3T3 fibroblasts
      and B16 melanoma cells; human epithelial EUE cells and mammary carcinoma MCF-7
      cells) were used. The expression of M1-RR antigen was found to correlate
      positively with the expression of Ki-67 and PCNA, and negatively with the
      expression of statin. During early G1 phase, M1-RR becomes detectable by specific
      antibodies relatively later compared to PCNA and Ki-67; therefore, the lack of
      immunopositivity for M1-RR cannot be taken as an absolute indication of cell
      quiescence in G0.

PMID- 9627221
TI  - Cytometric study of intracellular P-gp expression and reversal of drug
      resistance.
AB  - Expression of the multidrug resistance (MDR) phenotype is responsible for
      chemotherapy failure in numerous cancers. This phenotype is generally due to the
      expression of the mdr1 gene-encoded P-gp. Modulation of P-gp activity by
      chemotherapy has limited possibilities because of toxicity and poor specificity.
      In contrast, specific transcription blockage of the mdr1 gene can be obtained by
      oligonucleotides forming a triple helix structure at the DNA level. We used here
      immunofluorescence and both flow cytometry and image analysis to evaluate surface
      and total P-gp content in K562 MDR cells. The mdr1 mRNA content was measured by
      RT-PCR. We confirm the capacity of a 27-mer oligodeoxynucleotide, targeted to an
      mdr1 DNA fragment, to cause a 10-fold decrease in mdr1 mRNA level. However, this
      specific genetic inhibition was functionally limited because cellular growth was
      not modified in a cytotoxic environment. We found that total P-gp content was
      reduced in resistant cells treated with the mdr1-targeted oligonucleotide, while
      it remained in high levels on the cell surface, suggesting the existence of a
      large cytoplasmic pool of P-gp (approximately 50% of the total cellular P-gp).
      Moreover, when cycloheximide was used for 72 h to suppress protein synthesis,
      surface P-gp expression showed no decrease, whereas total P-gp was considerably
      lowered. A rapid 35% decrease in surface P-gp level was reached when resistant
      cells were treated for 24 h with brefeldin A, an inhibitor of intracellular
      protein trafficking. Simultaneously, the total P-gp level remained stable, thus
      indicating a probable accumulation of cytoplasmic P-gp, in agreement with the
      interruption of protein migration. We propose that the cytoplasmic P-gp pool
      could be a storage pool consumed for maintaining a steady-state level of surface
      P-gp. Cytometry could be a useful tool to study such a mechanism of P-gp
      trafficking and cellular distribution, which could explain the difficulties
      encountered in achieving stable and rapid effects of MDR reversal with
      oligonucleotides.

PMID- 9627222
TI  - Simple, fast method of detection apoptosis in lymphoid cells.
AB  - To facilitate the analysis of apoptotic cells, the present study proposes a new
      quantitative method based on the changes of light scatter properties of lymphoid
      cells undergoing apoptosis measured with a hematology analyzer. Peripheral blood
      lymphocytes from 40 chronic B-lymphocytic leukemia samples, five acute T
      lymphoblastic leukemia samples, three healthy donors and from T-cell lines
      Jurkat, SUB-T1 and SUP T8) were cultured during 72 hours in medium alone or in
      the presence of chlorambucil, fludarabine or theophylline, all compounds known to
      be apoptosis inducers, with or without adjunction of interleukin 4. Samples were
      run on a Bayer-H1 system and the percentage of apoptotic cells was evaluated by
      monitoring the lobularity index corresponding to the polymorphonuclear
      population. Results compared to the dUTP-fluorescein method by flow cytometry and
      dUTP-peroxidase labeling on slides (TUNEL) showed an excellent correlation (chi
      square test: P < 0.01). This method is reliable and simple and allows one to
      measure routinely the percentage of apoptotic lymphoid cells at short notice in a
      laboratory of hematology. This is especially valuable, particularly in testing
      the predictive value of in vitro drug-induced apoptosis before starting a
      chemotherapy protocol.

PMID- 9627223
TI  - 2,4 Dinitrophenol-uncoupling effect on delta psi in living hepatocytes depends on
      reducing-equivalent supply.
AB  - Mitochondrial uncouplers, such as 2,4 dinitrophenol (DNP), increase the cellular
      respiration by decreasing mitochondrial membrane potential (delta psi). We show
      that this respiratory effect can be transient or even prevented in isolated liver
      cells depending on the exogenous substrate used (dihydroxyacetone vs. octanoate
      or proline). Moreover the decrease in ATP/ADP ratio induced by DNP is partially
      restored by addition of octanoate or proline. By using rhodamine 123 (Rh123)
      monitored by flow cytometry in living hepatocytes, we were able to follow in time
      delta psi in such DNP-uncoupled cells incubated with various substrates. The
      ability of this method to evaluate delta psi changes was assessed by using
      myxothiazol (3.6 microM), an inhibitor of the b-c1 complex of the respiratory
      chain which decreased delta psi (65%), or oligomycin (6 microg/ml), an inhibitor
      of the F0F1-ATPase which increased it (50%). Although DNP induced a dose
      dependent decrease of delta psi, we found that octanoate or proline addition
      prevented such effect. We propose that octanoate or proline may counteract the
      uncoupling effect of DNP by providing a high supply of reducing equivalents to
      the respiratory chain.

PMID- 9627224
TI  - Impaired expression and function of signal-transducing zeta chains in peripheral
      T cells and natural killer cells in patients with prostate cancer.
AB  - Detection of functional, circulating T cells and NK cells may serve as a clinical
      test for the selection of individuals who can benefit from immunotherapy.
      Incidence of the T-cell receptor zeta (TCRdelta) chain within these populations
      appears to correlate with adequate effector cell function. In patients with
      advanced malignancy, the absence or reduced expression of delta chain has been
      documented. Flow cytometric analysis in the present study revealed a significant
      reduction in delta chain expression in peripheral blood lymphocytes (PBL) of 14
      of 22 prostate cancer patients (P < 0.000001) as compared to normal donors,
      apparent in both T cells (CD3+, CD4+, CD8+), and NK (CD16+) cells. Compared to
      normal donor PBL, patient PBL cultured in the presence of CD3 and CD28, also
      demonstrated reduced expression of CD69 and/or CD25, and in some cases, failed to
      activate at all. Furthermore, evidence of cell proliferation in activation
      stimulated patient PBL was muted: average PCNA positivity equaled 14%, a marked
      difference from what was observed in normal donors (P < 0.0002). In 8 of 16
      samples of PBL, where delta expression was originally low, delta levels returned
      to the normal range after 48 hour culture in serum-free medium, suggesting that
      the loss of delta is reversible and may be caused by a tumor-derived substance.
      These data support the premise that monitoring the expression of delta in a
      cancer patient may provide a unique insight into the immune status and
      functionality of the individual, with the potential to redirect or augment
      therapies and ultimately alter prognosis.

PMID- 9627225
TI  - EGF-induced redistribution of erbB2 on breast tumor cells: flow and image
      cytometric energy transfer measurements.
AB  - erbB2, a member of the epidermal growth factor (EGF) receptor-type tyrosine
      kinase receptor family, is overexpressed in breast carcinomas with poor
      prognosis. We examined the cell surface association of this receptor with itself
      and with other cell surface proteins by the Forster-type fluorescence resonance
      energy transfer using whole antibodies and Fab fragments. We found that erbB2
      molecules homoassociate in unstimulated SK-BR-3, BT474 and BT474-M (a metastatic
      version of the parent BT474 line) breast tumor cells, and that the interaction
      was enhanced by EGF treatment in suspensions of SK-BR-3 and BT474-M cells. BT474
      cells (with low EGF receptor expression) and attached SK-BR-3 cells do not
      respond to EGF. Image microscopic energy transfer measurements found considerable
      pixel-by-pixel heterogeneity in the homoassociation state of erbB2. In accordance
      with the EGF-induced redistribution of erbB2, EGF receptor was found to be in
      close proximity to erbB2 in FRET measurements. By labeling different epitopes on
      erbB2 and the lipid bilayer, we were able to prepare an epitope map of erbB2
      molecule. Our data suggest the existence of dynamic cell surface patterns of
      erbB2 and point to functions fulfilled by these molecular complexes.

PMID- 9627227
TI  - Heterogeneous photobleaching in confocal microscopy caused by differences in
      refractive index and excitation mode.
AB  - The photobleaching of fluorescence emission during confocal laser scanning was
      studied on well-defined, stained objects [microspheres of polystyrene or
      fluorescent gels of fluorescein isothiocyanate (FITC)-labeled dextran] and on
      biological samples. X,Y laser scanning with confocal microscopy induces
      fundamental differences in exposure rate and time in different z-planes
      orthogonal to the optical axis. A heterogeneous bleaching rate was observed at
      different focal levels in the polystyrene spheres and in the gels. This
      phenomenon can be caused by refractive index differences or is correlated with a
      photobleaching rate, which is dependent not only on the excitation light
      intensity but also on the photon flux (total intensity per unit of time).
      Heterogeneous excitation induced by refractive index differences results in
      photobleaching differences but will not necessarily cause heterogeneous emission
      intensity. Altered emission originating from altered excitation will be
      annihilated if the emitted light returns to the image plane along the same
      inverse path, compensating for the proportional increase or decrease in
      excitation intensity with an increased or decreased emission intensity. High
      numerical aperture or increased scanning speed increases the photobleaching rate.
      This leads to the conclusion that photobleaching in confocal scanning laser
      microscopy is dependent on photon energy flux density (joule/m2s).

PMID- 9627226
TI  - New technique for high resolution DNA sizing in epi-illumination.
AB  - We present a high-resolution DNA-sizing technique based on the principles of flow
      cytometry, using a high numerical aperture objective and epi-illumination. The
      new technique, designed for small fluorescing samples/particles (sub-micron
      diameter) suspended in a weakly fluorescent medium, makes use of an additional
      focus for high-precision particle localisation. This way, only those particles
      are considered that flow exactly through a well-defined volume. Results are
      presented for fluorescent beads, as well as for YOYO-stained plasmids containing
      5,500 basepairs. The latter were measured with 6.2% resolution, setting a new
      limit to flow-based sizing of DNA.

PMID- 9627228
TI  - Analysis of intracellular Th1 cytokine secretion data using parametric
      methodology.
AB  - Flow cytometric methods are widely used for analyzing cytokine release from
      immune cell populations. However, difficulties are frequently encountered in the
      analysis of flow cytometric data from intracellular cytokine staining because the
      cytokine positive and cytokine negative histograms overlap considerably. This
      study compares models containing Gaussian, Giddings, Haarhoff-van der Linde (HVL)
      and Weibull distributions for fitting flow cytometric intracellular cytokine
      histogram peaks. The results show that flow cytometric data for the Th1
      cytokines, interferon-gamma and interleukin-2, in peripheral blood are well
      described by a model consisting of the sum of two log-normal distributions but
      the other distributions tested also showed satisfactory fits. The model-based
      approach may potentially eliminate the need to use markers derived from isotype
      control staining. The results obtained using peak fitting were also compared to
      the widely practised 99% division line or marker method. The percent positive
      calculated using the 99% division line or marker methods correlates poorly with
      the percent area under the cytokine-positive peak. However, when the model is
      used to calculate a cytokine-positive percentage analogous to that determined by
      the 99% division line or marker method, the two methods correlate well.

PMID- 9627229
TI  - Surgical labyrinthectomy in the older patient.
AB  - OBJECTIVE: Ablation of vestibular function is a highly efficacious option in the
      treatment of disabling vertigo arising from unilateral labyrinthine dysfunction.
      Regardless of the method used to ablate vestibular function, permanent
      posttreatment impairment of the balance function will develop in a number of
      treated patients. Many physicians who are involved in the care of the older
      patient with episodic vertigo are reluctant to recommend or perform a vestibular
      ablation procedure, because this treatment may result in permanent
      disequilibrium, which may be more detrimental to the older patient than the
      episodic vertigo. This study evaluates the outcome in older patients who
      underwent unilateral surgical labyrinthine ablation. METHODS: A retrospective
      analysis was done of the cases of 30 patients, all more than 60 years old, who
      underwent unilateral vestibular ablation because of disabling episodic vertigo by
      either transmastoid labyrinthectomy (n=22) or transcanal labyrinthectomy (n=8).
      RESULTS: Episodic vertigo was controlled in 95.5% of the patients in the
      transmastoid labyrinthectomy group and in 100% of those in the transcanal
      labyrinthectomy group. Postoperative imbalance was present in 22.7% of patients
      in the transmastoid labyrinthectomy group and in 62.5% of those in the transcanal
      labyrinthectomy group. CONCLUSIONS: Vestibular ablation is a viable option in the
      treatment of disabling vertigo in the older patient. A transmastoid
      labyrinthectomy may be preferable to a transcanal labyrinthectomy because the
      incidence of permanent posttreatment imbalance is less with a transmastoid
      labyrinthectomy.

PMID- 9627230
TI  - Postauricular myocutaneous flap in otologic surgery.
AB  - Management of a large mastoid defect resulting from skull base operations or
      extensive surgical procedures because of chronic ear disease continues to
      challenge the otologic surgeon. Various local muscle or periosteal rotation flaps
      have been used to help reduce the size of the postoperative mastoid cavity. With
      these techniques there are problems with flap retraction and epithelization that
      may result in delayed healing or chronic drainage. Closure of the ear canal and
      tissue obliteration of the mastoid results in a maximal conductive hearing loss.
      A postauricular myocutaneous flap based on the occipital artery and
      sternocleidomastoid muscle has been used effectively to reconstruct mastoid
      defects after both surgical procedures for chronic ear disease and skull base
      operations. The skin muscle flap reduces the mastoid cavity and promotes rapid
      healing of the surgical defect. Although postauricular myocutaneous flaps have
      been found to be reliable, their viability may be compromised by arterial
      embolization used in larger glomus tumors. Indications for and creation of a
      postauricular myocutaneous flap, with results in 18 cases, are presented.

PMID- 9627231
TI  - Risk of progressive sensorineural hearing loss and Meniere's disease after breast
      implantation.
AB  - OBJECTIVE: The association of various immunologic abnormalities with the presence
      of silicone breast implants in women has been described. In addition, some
      studies report a correlation between autoimmune disorders and silicone breast
      implants, whereas other studies indicate no difference in the incidence of
      disease between women with silicone breast implants and control groups. Until
      recently, no reports had attempted to identify an association between silicone
      breast implants and hearing impairment. A recent study suggested a possible
      correlation between prior silicone breast implants and the development of various
      forms of hearing loss. This study tried to determine whether such a correlation
      could be duplicated. METHODS: To determine whether such a correlation could be
      established, we studied 119 female patients with either Meniere's disease or
      progressive sensorineural hearing loss and 100 age-matched healthy controls.
      Subjects completed questionnaires that provided various types of information,
      including the presence or absence of previous silicone breast implants. Serum
      from all 119 patients with Meniere's disease and progressive sensorineural
      hearing loss had been subjected to previous Western blot testing for reactivity
      to a 68 kD protein associated with certain forms of autoimmune hearing loss.
      RESULTS: Results indicated no significant difference in frequency of prior
      silicone breast implants among the patients with Meniere's disease, patients with
      sensorineural hearing loss, or controls. The presence or absence of the 68 kD
      protein also was not significantly relevant to the frequency of silicone breast
      implants. CONCLUSIONS: Our data did not show evidence of a significant
      relationship between the presence of silicone breast implants and later
      development of Meniere's disease, progressive sensorineural hearing loss, or
      positive 68 kD serum.

PMID- 9627232
TI  - Acoustic mechanisms: canal wall-up versus canal wall-down mastoidectomy.
AB  - The contribution of the middle ear air spaces to sound transmission through the
      middle ear in canal wall-up and canal wall-down mastoidectomy was studied in
      human temporal bones by measurements of middle ear input impedance and sound
      pressure difference across the tympanic membrane for the frequency range 50 Hz to
      5 kHz. These measurements indicate that, relative to canal wall-up procedures,
      canal wall-down mastoidectomy results in a 1 to 5 dB decrease in middle ear sound
      transmission below 1 kHz, a 0 to 10 dB increase between 1 and 3 kHz, and no
      change above 3 kHz. These results are consistent with those reported by Gyo et
      al. (Arch Otolaryngol Head Neck Surg 1986;112:1262-8), in which umbo displacement
      was used as a measure of sound transmission. A model analysis suggests that the
      reduction in sound transmission below 1 kHz can be explained by the smaller
      middle ear air space volume associated with the canal wall-down procedure. We
      conclude that as long as the middle ear air space is aerated and has a volume
      greater than 0.7 ml, canal wall-down mastoidectomy should generally cause less
      than 10 dB changes in middle ear sound transmission relative to the canal wall-up
      procedure.

PMID- 9627233
TI  - Aural symptoms and hearing loss in patients with lupus.
AB  - OBJECTIVE: Systemic lupus erythematosus causes widespread tissue injury from
      deposition of immune complexes. The prevalence of aural symptoms in this disease
      was evaluated. METHODS: The presence of tinnitus, hearing loss, and fluctuating
      hearing was evaluated by a self-directed questionnaire in patients aged 65 or
      less from a lupus clinic. Patients reporting aural symptoms were compared with
      those reporting none, by use of demographics and disease duration. Comparison was
      also made with historic serologic data. Audiometry was offered to all patients
      with lupus reporting aural symptoms and was completed in 10. RESULTS: Twenty-six
      (31%) of 84 patients with lupus reported aural symptoms. Patients reported a
      combination of symptoms: unilateral hearing loss with or without tinnitus in 13
      (15%) of 84 and bilateral hearing loss with or without tinnitus in 14 (17%) of
      84. No statistical difference was measured between symptomatic and asymptomatic
      patients when compared by average age, duration of disease, history of noise
      exposure, head trauma, and infectious ear diseases. Statistically significant
      differences were detected only when comparing average creatinine and C3 levels.
      Of those patients tested by audiometry, 7 of 10 had abnormal pure-tone
      thresholds. Asymmetric findings were present in 6 of these 7 patients tested.
      CONCLUSION: Aural symptoms are prevalent among patients with lupus. Asymmetric
      symptoms and hearing loss are most common. The cause may relate to immune-complex
      disease and/or vasculitis.

PMID- 9627234
TI  - Isolated cervical tuberculosis in patients with HIV infection.
AB  - OBJECTIVE: Tuberculosis isolated to the head and neck region is common in
      patients with HIV infection. However, the management of isolated head and neck
      tuberculosis has not been reported in the literature. This study was done to
      describe the characteristics of tuberculosis isolated to the head and neck region
      in patients infected with HIV and to detect differences in presentation and
      diagnostic management based on the status of HIV infection at presentation.
      METHODS: A retrospective study was performed including 38 patients infected with
      HIV who were seen with tuberculosis isolated to the head and neck region at two
      tertiary care centers during a 10-year period. These patients were divided into
      two groups on the basis of the HIV status at presentation, which indirectly
      reflects the level of immunosuppression. Group 1 included 11 patients (29%) with
      AIDS at presentation. Group 2 included 27 patients (71%) with HIV infection but
      not AIDS. RESULTS: The cervical lymphatics were the most common site for isolated
      head and neck tuberculosis (89%), with the supraclavicular nodes most often
      involved (53%). Extralymphatic involvement was less common (11%), but involved a
      variety of anatomic locations (skin, spinal cord, larynx, parotid). The
      presenting history and physical examination had a low sensitivity for
      tuberculosis in patients with HIV infection, mainly because of the presence of
      multiple confounding factors. Purified protein derivative testing was highly
      sensitive for tuberculosis in patients with HIV infection alone (61 %); however,
      its usefulness was diminished in patients with AIDS (14%; p=0.03). Fine-needle
      aspiration biopsy was 94% sensitive for diagnosing tuberculosis and was not
      affected by the status of HIV infection. Surgical biopsy was the gold standard
      for diagnosing tuberculosis but was associated with chronically draining fistulas
      in a significant number of cases (14%). CONCLUSIONS: These data suggest that
      tuberculosis should be considered in the differential diagnosis of all head and
      neck lesions in patients infected with HIV, even in the absence of pulmonary
      involvement. Purified protein derivative testing should be done liberally in
      these patients, with realization that the sensitivity of purified protein
      derivative testing is reduced in patients with AIDS. Fine-needle aspiration
      biopsy should be the key diagnostic test in this patient population, with open
      surgical biopsy reserved for highly suspicious cases in which other measures were
      not diagnostic.

PMID- 9627235
TI  - Quantitative and qualitative analysis of tracheoesophageal voice after pectoralis
      major flap reconstruction of the neopharynx.
AB  - Although tracheoesophageal voice restoration is accepted after reconstruction of
      the neopharynx with the pectoralis major myocutaneous flap, the character of such
      voice is not well described. Six patients reconstructed with the pectoralis major
      flap after laryngopharyngectomy underwent successful voice restoration with the
      Blom-Singer prosthesis. Voice was evaluated by a standardized protocol and
      compared with voices of control subjects treated with total laryngectomy and
      similar voice restoration. The patients with pectoralis major flaps produced
      similar intensity levels for soft voice (53.7 dB vs. 55.6 dB) and loud voice
      (61.3 dB vs. 65.3 dB) when compared with controls (p > 0.05). No significant
      differences (p > 0.05) were noted for fundamental frequency (F0) between patients
      with pectoralis major flaps and controls for soft (62.3 Hz vs. 85.4 Hz) and loud
      (109.8 Hz vs. 133.8 Hz) voice. Jitter was also comparable. Trained and naive
      listeners completed qualitative analyses for 10 parameters and judged that
      control patients had significantly better voice for most parameters. This finding
      demonstrates that dependable voice is attainable after pectoralis major flap
      reconstruction of the neopharynx. Although this voice does not differ
      significantly from voice after standard laryngectomy for acoustic parameters,
      perceptual analysis does reveal significant differences.

PMID- 9627236
TI  - Incidence of deep venous thrombosis and pulmonary embolism in otolaryngology-head
      and neck surgery.
AB  - OBJECTIVE: Postoperative deep venous thrombosis and pulmonary embolus are major
      causes of morbidity and mortality in patients undergoing surgical procedures. In
      contrast to other surgical fields, the incidence of these life-threatening
      conditions has not been studied in our specialty. The purposes of this study were
      to elucidate the incidence of deep venous thrombosis and pulmonary embolus in
      patients after otolaryngologic operations and to identify specific risk factors
      that may contribute to the development of these conditions. METHODS: A
      retrospective analysis was done of 12,805 total operations on adults done by the
      Department of Otolaryngology at our institution from January 1987 to December
      1994 to determine the number of patients in whom postoperative deep venous
      thrombosis and pulmonary embolus developed. Patients in whom a postoperative
      thromboembolic event developed after an otolaryngologic surgical procedure were
      identified by the medical records department with use of an abstracting database.
      This search cross-referenced disease-specific codes for otolaryngologic
      procedures with the codes for deep venous thrombosis and pulmonary embolus to
      identify the 34 patients in this report. Results (rounded to the nearest decimal
      point) were then categorized according to the different subspecialties within
      otolaryngology, and appropriate statistical analysis tests were performed on the
      resulting data. RESULTS: Thirty-four patients with postoperative deep vein
      thrombosis were identified during the study period, for an overall incidence of
      0.3%. Of these 34 patients, 24 also had a pulmonary embolus for an overall
      incidence of 0.2%. The incidence of deep venous thrombosis (and pulmonary
      embolus) in the subspecialties was as follows: head and neck surgery, 0.6%
      (0.4%); otology/neurotology, 0.3% (0.2%); head and neck trauma and plastic
      surgery, 0.1% (0.1%); and general otolaryngology, 0.1% (0.04%). Only the
      patient's age and the presence or absence of pneumatic compression devices were
      identified as independent risk factors for the development of a thromboembolic
      event. CONCLUSIONS: Postoperative pulmonary embolus is a rare occurrence in the
      field of otolaryngology-head and neck surgery. When it does occur, it causes
      significant morbidity and increases the cost of care for that patient. We discuss
      our approach to categorizing patients into low-, intermediate-, and high-risk
      groups, as well as prophylaxis against pulmonary embolus.

PMID- 9627237
TI  - Ondansetron versus droperidol or placebo to prevent nausea and vomiting after
      otologic surgery.
AB  - This study compares the preoperative administration of ondansetron with that of
      droperidol or saline solution for the prevention of nausea and vomiting in
      otologic surgery patients. A total of 120 otherwise healthy individuals were
      randomly assigned to receive either saline solution, ondansetron (4 mg
      intravenously), or droperidol (25 microg/kg intravenously) before anesthetic
      induction. Intraoperative and postanesthesia care unit times were recorded along
      with incidence of nausea, vomiting, pain, nausea and recovery scores, and the
      administration of rescue antiemetics. Similar assessments were made during the
      next 24 hours. Demographics were similar, but more males received ondansetron.
      Anesthetic recovery scores were lower after administration of droperidol than
      after ondansetron. Incidence of nausea was similar between groups, but severity
      was greater with placebo and droperidol than with ondansetron. More vomiting
      occurred with placebo than with ondansetron or droperidol. No intergroup
      differences in rescue antiemetic administration were noted, however. Twenty-four
      hours later, more patients receiving placebo had nausea or vomited than patients
      receiving droperidol or ondansetron. Fewer women in the ondansetron group vomited
      than in the other two groups. Ondansetron 4 mg intravenously is as effective as
      droperidol and better than saline solution in preventing nausea and vomiting in
      patients undergoing otologic surgery. No cost advantage as determined by lower
      use of rescue antiemetics or shorter postanesthesia care unit times was noted
      after ondansetron therapy.

PMID- 9627238
TI  - Psychological distress: linking impairment with disability in facial neuromotor
      disorders.
AB  - The relationship between facial neuromotor system impairment, disability, and
      psychological adjustment is not well understood. This study was designed to
      explore the relation between impairment and disability and the impact of
      psychological adjustment on the relation for individuals with disorders of the
      facial neuromotor system. We studied outpatients (n=48; mean age, 49.0; SD=16.3;
      range, 18 to 84 years) with a facial neuromotor disorder and acute or chronic
      facial paralysis. Measures of impairment (Facial Motion Assay, House-Brackmann
      scale, and Facial Grading System), disability (Facial Disability Index, physical
      and social well-being subscales), and psychological adjustment (Beck Anxiety
      Inventory, Beck Depression Inventory) were administered. Bivariate correlations
      between impairment and disability measures indicated impairment was positively
      correlated with physical and social disability (r=0.44, p < 0.01; r=0.39, p <
      0.05, respectively). Stepwise regression analysis to predict disability indicated
      physical disability was predicted by impairment and the interaction of impairment
      and psychological distress (R2=0.425; F=12.57; df=2, 34; p=0.002). Psychological
      distress, and not impairment and the interaction of impairment and distress, was
      the single predictor of social disability (R2=0.274; F=13.23; df=1, 35; p=0.001).
      Psychological distress was a moderator of the relation between impairment and
      physical disability and a mediator of the relation between impairment and social
      disability for individuals with facial neuromotor disorders. Assessment and
      interventions targeted for psychological distress in addition to interventions
      targeted for impairments appear warranted to effectively reduce the disability
      associated with facial neuromotor disorders.

PMID- 9627239
TI  - Comparison of Multi-Test device skin testing and modified RAST results.
AB  - The initial purpose of this study was to determine the potential correlation
      between allergy test results obtained with the Multi-Test skin testing method and
      the radioallergosorbent test (RAST) blood test (used as a "standard"). Twenty
      patients with a history and physical examination findings suggestive of inhalant
      allergy underwent both a Multi-Test system screen (14 antigens plus histamine and
      glycerine controls) and RAST testing. The relationship between wheal size and
      Multi-Test system grade for each antigen and the corresponding RAST class was
      studied. The correlation between positive Multi-Test system and RAST results was
      poor, with an average agreement by antigen of 56.26% and overall agreement of
      67.86%. However, the overall agreement between negative Multi-Test system results
      (< or =1+) and negative RAST results (< or =class 1) was 95.15%, with an average
      agreement by antigen of 83.99%. On the basis of results of this preliminary
      study, it appears that a negative Multi-Test system result indicates that
      significant inhalant allergy is unlikely, whereas a positive Multi-Test system
      result necessitates follow-up with more definitive testing by additional skin
      testing or RAST.

PMID- 9627240
TI  - Initial report on postoperative healing after endoscopic sinus surgery with the
      microdebrider.
AB  - Synechiae formation is a frequent occurrence after endoscopic sinus surgery and
      may cause symptomatic sinus outflow tract obstruction. Various means are used to
      reduce the incidence of synechiae formation. These include meticulous operative
      technique, partial middle turbinate resection, middle meatus spacers or stents,
      and postoperative debridement. The microdebrider is a powered rotary shaving
      device that precisely resects tissue, minimizing inadvertent mucosal trauma and
      stripping. We present 40 cases of endoscopic sinus surgery performed with the
      microdebrider. Patients had at least a 5-month follow-up and demonstrated rapid
      mucosal healing, minimal crust formation, and a low incidence of synechiae
      formation. These initial data suggest that the microdebrider may be advantageous
      in surgery for chronic sinusitis.

PMID- 9627241
TI  - Comparison of inflammatory cell profile and Th2 cytokine expression in the
      ethmoid sinuses, maxillary sinuses, and turbinates of atopic subjects with
      chronic sinusitis.
AB  - Chronic sinusitis is a common disease characterized by persistent inflammation of
      the sinus mucosa. This study was undertaken to investigate immunopathologic
      findings in biopsy specimens from the ethmoid sinuses, maxillary sinuses, and
      inferior nasal turbinates of 14 allergic subjects with chronic sinusitis. The
      composition of the inflammatory infiltrate in the three tissue sites was examined
      by immunocytochemistry with anti-CD3 (total T cells), anti-CD4 (helper T cells),
      anti-CD8 (suppressor T cells), anti-MBP (eosinophils), antitryptase (mast cells),
      and antichymase (mast cells) antibodies. These revealed a significant increase in
      the T-cell helper/suppressor ratio and eosinophils in the ethmoid sinus mucosa
      compared with those in the maxillary sinus mucosa and the inferior turbinate.
      Eosinophil numbers were also higher in the maxillary sinus than in the inferior
      turbinate. Mast cells were present in significantly higher numbers in the ethmoid
      sinus and inferior turbinate biopsy sections than in the maxillary sinus. With
      antisense, radiolabeled riboprobes, we used in situ hybridization to examine the
      expression of interleukin-4 and interleukin-5 transcripts. The density of cells
      expressing interleukin-4 transcripts was significantly higher in the inferior
      turbinate biopsy sections than in those from the ethmoid and maxillary sinuses.
      In addition, the number of interleukin-4 mRNA-positive cells was higher in the
      ethmoid than in the maxillary sinus mucosa. The density of interleukin-5 mRNA
      positive cells was significantly higher in the ethmoid and maxillary sinuses than
      in the inferior turbinate. The results of this study indicate (1) a more intense
      inflammatory response in the ethmoid sinus than in the maxillary sinus and
      inferior turbinate in allergic chronic sinusitis and (2) different inflammatory
      responses in the upper airways that are dependent on the anatomic site. These
      findings have potential implications in the design of new therapeutic
      interventions for allergic chronic sinusitis.

PMID- 9627242
TI  - Preliminary results of the use of indole-3-carbinol for recurrent respiratory
      papillomatosis.
AB  - OBJECTIVE: We report the preliminary results of a phase I trial using indole-3
      carbinol for the treatment of recurrent respiratory papillomatosis. Indole-3
      carbinol is a chemical that is found in high concentrations in cruciferous
      vegetables and has been shown to alter the growth pattern of recurrent
      respiratory papillomatosis cell cultures and to be effective in an in vivo animal
      model of recurrent respiratory papillomatosis. METHODS: Eighteen patients were
      treated with oral indole-3-carbinol and had a minimum follow-up of 8 months and a
      mean follow-up of 14.6 months. All patients received indole-3-carbinol, and
      outcome measures included a change in papilloma growth rate and the need for
      surgery during treatment compared with before treatment. All patients had serial
      examinations with videoendoscopy to document papilloma location and growth rate.
      RESULTS: Thirty-three percent (6 of 18) of the study patients had a cessation of
      their papilloma growth and have not required surgery since the start of the
      study. Six patients have had reduced papilloma growth rate, and 6 (33%) patients
      have shown no clinical response to indole-3-carbinol. Indole-3-carbinol affects
      the ratio of hydroxylation of estradiol; changes in the ratios of urinary 2
      hydroxylation and 16-hydroxylation of estradiol caused by indole-3-carbinol
      correlated well with clinical response. No major complications or changes in the
      children's growth curve were noted. CONCLUSIONS: The preliminary results of
      treating recurrent respiratory papillomatosis with indole-3-carbinol holds
      promise. Longer follow-up of this patient group and a blinded, controlled trial
      are required. We conclude that indole-3-carbinol appears to be safe and well
      tolerated and may be an efficacious treatment for recurrent respiratory
      papillomatosis.

PMID- 9627243
TI  - Transforming growth factor-alpha with insulin induces proliferation in rat
      utricular extrasensory epithelia.
AB  - Hair cell loss in the human inner ear leads to sensorineural hearing loss and
      vestibular dysfunction. Recent studies suggest that exogenous addition of growth
      factors, for example, transforming growth factor-alpha with insulin, may
      stimulate the production of new supporting cells and hair cells in the mature
      mammalian vestibular sensory epithelium. Before any growth factor can be
      seriously considered for the treatment of clinical problems related to hair cell
      loss, its effects on the extrasensory epithelia must also be fully explored. The
      aim of this study was to determine whether transforming growth factor-alpha and
      insulin stimulate cell proliferation in rodent vestibular extrasensory epithelia.
      The cell proliferation marker, tritiated thymidine, was infused along with
      transforming growth factor-alpha, insulin, or transforming growth factor-alpha
      plus insulin into the inner ears of adult rats via osmotic pumps. Effects of the
      test agents were assessed on normal and drug-damaged utricles. Drug damage was
      produced by delivering gentamicin directly into the inner ear before the infusion
      of test agent. Animals were killed 4 or 10 days after pump placement. Utricles
      were sectioned, processed for autoradiography, and examined for labeled cells
      within the extrasensory epithelia. In normal animals, transforming growth factor
      alpha plus insulin stimulated DNA synthesis in all regions of the extrasensory
      epithelia, suggesting that these agents are mitogenic for these tissues.

PMID- 9627244
TI  - Histopathology of human temporal bone after cis-platinum, radiation, or both.
AB  - Preserving organs by use of multiple modalities has become protocol in treating
      squamous cell carcinomas of the head and neck, but cis-platinum and radiation can
      impair hearing. To determine the effect of cis-platinum, radiation, or a
      combination of these treatments on the temporal bone, we studied histopathologic
      slides of 15 human temporal bones: four after cis-platinum, five after radiation,
      two after combined treatment, and four from normal controls. Hair cells and cells
      in spiral ganglia were counted in reconstructed organs of Corti. Lumen-to
      diameter indexes in arterioles near facial nerves were quantified for four normal
      controls and seven irradiated patients. Available audiograms were compared.
      Decreased spiral ganglion cells, loss of inner and outer hair cells, and atrophy
      of stria vascularis were demonstrated in groups receiving cis-platinum,
      radiation, and combinations, compared with age-matched controls. Arterioles
      around facial nerves demonstrated fibrinous clots within the intima, endothelial
      proliferation, and hypertrophy and fibrosis of vascular walls in smooth muscle.
      Fibrosis in connective tissue was clearly progressive after radiation. Cis
      platinum and radiation can contribute to otologic sequelae, including
      sensorineural hearing losses, vascular changes, serous effusion, or fibrosis.
      Prophylactic treatments and techniques to deliver them should be considered for
      protection of temporal bones and preservation of hearing after oncologic
      modalities.

PMID- 9627245
TI  - Obstructive sleep apnea treatment outcomes pilot study.
AB  - Approximately 40 million Americans have chronic sleep disorders, the most serious
      of which is obstructive sleep apnea. The goals of this research were to serve as
      a demonstration project for a multicenter treatment outcomes research project for
      patients with obstructive sleep apnea. A clinical-severity staging system was
      created to control for important differences in the severity of sleep apnea among
      the enrolled patients. A disease-specific quality-of-life measure was used in
      this project to measure, from the patient's perspective, important pretreatment
      and posttreatment physical, functional, and emotional aspects of obstructive
      sleep apnea. Adults with apnea indexes greater than 5 who had not previously
      undergone uvulopalatoplasty were eligible. In total 142 patients were enrolled
      from eight otolaryngology practices. The mean age was 48 years, 112 were men, and
      114 were white. The mean pretreatment apnea index was 40.0, and the mean
      respiratory distress index was 60.5. Seventy-one patients received continuous
      positive airway pressure, and 48 patients received surgery. Outcomes were
      assessed from scores on patient-based general and disease-specific health status
      measures 4 months after enrollment. The short duration of follow-up and limited
      number of patients undergoing posttreatment polysomnograms prohibit any analysis
      of treatment effectiveness. Nevertheless, this research represents a step forward
      for the support of future outcomes research projects by organized otolaryngology.

PMID- 9627246
TI  - Esophageal presentation of cicatrical pemphigoid.

PMID- 9627247
TI  - Angiolipoma presenting as a nasal mass.

PMID- 9627248
TI  - Intraductal papilloma of the minor salivary gland involving the nasal cavity: is
      it a distinct histopathologic entity?

PMID- 9627249
TI  - Escherichia coli osteomyelitis of the skull base.

PMID- 9627250
TI  - Surgical management of nasal and sinus sarcoidosis.

PMID- 9627251
TI  - Familial recurrent facial paresis: four generations.

PMID- 9627252
TI  - Necrotizing granulomatous inflammation of the superior vestibular nerve mimicking
      an acoustic neuroma.

PMID- 9627253
TI  - Susac syndrome.

PMID- 9627254
TI  - Isolated laryngeal sarcoidosis.

PMID- 9627256
TI  - Granular cell tumor of the larynx presenting with airway obstruction.

PMID- 9627255
TI  - Central giant cell granuloma of the hard palate.

PMID- 9627257
TI  - Endoscopic management of an inverted nasal papilloma in a child.

PMID- 9627258
TI  - The use of preoperative lidocaine to prevent stridor and laryngospasm after
      tonsillectomy and adenoidectomy.
AB  - The most important complications from tonsillectomy and adenoidectomy are
      bleeding, stridor, and laryngospasm. This controlled, double-blind study was
      designed to investigate the effects of topical and intravenous lidocaine on
      stridor and laryngospasm. A total of 134 patients scheduled for elective
      tonsillectomy and/or adenoidectomy were randomly separated into four groups. In
      the topical lidocaine group 4 mg/kg of 2% lidocaine was applied to subglottic,
      glottic, and supraglottic areas before endotracheal intubation. Normal saline
      solution was used topically for the first control group. In the intravenous
      lidocaine group, patients were given 1 mg/kg of 2% lidocaine before extubation,
      and the same amount of 0.9% NaCl was given to the second control group.
      Postoperative stridor, laryngospasm, cyanosis, bleeding, sedation degree, and
      respiratory depression were observed, and plasma lidocaine levels were measured.
      Both topical and intravenous lidocaine groups revealed less stridor and
      laryngospasm than the control groups, and no difference was found between the
      topical and intravenous lidocaine groups except the higher sedation scores in the
      early postoperative period for the intravenous lidocaine group.

PMID- 9627259
TI  - A new dosage regimen for topical application of ciprofloxacin in the management
      of chronic suppurative otitis media.
AB  - The clinical and bacteriologic efficacy of topically applied ciprofloxacin was
      studied in 60 patients with chronic suppurative otitis media. Two hundred fifty
      and 125 microg/ml concentrations of ciprofloxacin solutions were given to two
      groups of patients. The duration of therapy was determined according to the
      clinical cure at follow-up. More than 21 days of therapy was not needed in any
      patient. The clinical cure rate with 250 microg/ml ciprofloxacin was 78.1% at 14
      days and with 125 microg/ml it was 83.3%. However, a 100% clinical cure rate and
      complete bacteriologic eradication was obtained in 21 days in both groups. In
      each group only one patient had otomycosis by the fourteenth day of therapy,
      although ear discharge had ceased. It was concluded that 125 microg/ml
      ciprofloxacin could be applied as successfully as 250 microg/ml, and the duration
      of therapy had to be at least 14 days. This new dosage regimen can be adopted as
      an optimal dosage for ototopical application of ciprofloxacin in chronic
      suppurative otitis media. It will also obviously decrease the expense of therapy.

PMID- 9627260
TI  - Lectin histochemistry of laryngeal squamous cell carcinomas.
AB  - A panel of five biotinylated lectins was applied to study the presence and
      distribution of membrane carbohydrate residues in the normal laryngeal epithelium
      and in laryngeal squamous cell carcinomas (SCCs) of 86 patients with the avidin
      biotin peroxidase complex technique. The lectin-binding pattern of well
      differentiated SCCs was comparable to that of the spinous cells of the normal
      laryngeal epithelium. In the less differentiated SCCs, staining of the
      keratinocyte plasma membrane with lectins was either reduced or absent,
      indicating a decline in the glycosylation of cell surface glycoconjugates. The
      lectins applied here could be used in the rapid assessment of less-differentiated
      areas within a laryngeal SCC, but they cannot be regarded as reliable markers of
      laryngeal keratinocytes undergoing malignant transformation.

PMID- 9627261
TI  - Box and whisker plots for graphic presentation of audiometric results of
      conductive hearing loss treatment.
AB  - The Committee on Hearing and Equilibrium of the American Academy of
      Otolaryngology-Head and Neck Surgery has published guidelines for the reporting
      of audiometric results of middle ear interventions. It recommends the reporting
      of several audiometric variables by means of two summary parameters: means and
      standard deviation. This article advocates the use of other summary statistics,
      namely the median, quartiles, and extremes, because they do not require a normal
      distribution of the audiometric data and they are not sensitive to variations of
      the extreme values. On the basis of the exploratory data analysis, we propose a
      graphic method to present the Committee's variables in terms of their summary
      statistics. This "multiple box and whisker plot" offers a detailed and accurate
      overview of six variables in one graph.

PMID- 9627262
TI  - Completion thyroidectomy for differentiated thyroid carcinoma.
AB  - Completion thyroidectomy is performed because of a deferred diagnosis of
      differentiated carcinoma of the thyroid or a significant thyroid remnant after
      initial operation. During a period of 6 years, data from 40 patients with
      differentiated thyroid carcinoma undergoing completion thyroidectomy were
      retrospectively reviewed. There were 4 men and 36 women (1:9), and the average
      age was 39.6+/-1.9 years (range, 20 to 62 years). The indications for the initial
      surgery were a solitary thyroid nodule in 36 (90%) patients, multinodular goiter
      in 3 (7.5%) patients, and Graves' disease in 1 (2.5%) patient. Three patients
      underwent completion thyroidectomy during the same hospital stay. In the
      remaining 37 patients, completion thyroidectomy was performed 4 to 252 days
      (44.1+/-7.8 days) after the initial operation. The length of hospital stay for
      the initial operation was not different from that for completion thyroidectomy
      (5.1+/-0.3 days vs. 5.2+/-0.3 days). The length of time needed to accomplish the
      initial operation was not different from that required for the completion
      thyroidectomy (122+/-7.5 minutes vs. 110.8+/-5.9 minutes). There was no 30-day
      perioperative mortality. The postoperative morbidity in completion thyroidectomy
      consisted of transient hypoparathyroidism in 3 (7.5%) patients, permanent
      hypoparathyroidism in 1 (2.5%) patient, transient recurrent laryngeal nerve palsy
      in 1 (2.5%) patient, and permanent recurrent laryngeal nerve palsy in 1 (2.5%)
      patient. On the other hand, one transient recurrent laryngeal nerve palsy and one
      transient hypoparathyroidism occurred at the initial operation. Completion
      thyroidectomy is a safe procedure to remove the thyroid remnant.

PMID- 9627263
TI  - Influence of the multichannel cochlear implant on vestibular function.
AB  - Vestibular function was examined in 55 adult patients who underwent cochlear
      implant surgery. The percentages of the patients with normal results on an
      optokinetic nystagmus test and eye-tracking test before surgery were 85% and 82%,
      respectively. A caloric stimulation test was performed before surgery, and 67% of
      patients showed hypofunction or afunction. This same test was performed
      approximately 1 month after surgery, and 38% of patients showed functional
      deterioration. After surgery 47% of the patients reported some kind of subjective
      dizziness. The characteristics of dizziness were divided into three types: early,
      prolonged, and delayed. Fifty-eight percent of the patients had early type, 34%
      had prolonged type, and 8% had the delayed type. Eighteen percent of the patients
      felt dizziness when they used the implant device, indicating that electrical
      current spread from the implant device to the vestibular nerve. The other 82% of
      the patients did not report any relationship between the use of their cochlear
      implants and dizziness.

PMID- 9627264
TI  - Hyponasality caused by retronasopharyngeal air as a symptom of pneumomediastinum.

PMID- 9627265
TI  - A rare case of nasal glioma in adult age.

PMID- 9627266
TI  - Congenital granular cell tumor in the newborn.

PMID- 9627267
TI  - Battle's sign in temporal bone trauma.

PMID- 9627268
TI  - Electrocochleography in retrosigmoid vestibular nerve section for intractable
      vertigo.

PMID- 9627269
TI  - Primary peripheral T-cell lymphoma of the acoustic nerve.

PMID- 9627270
TI  - Gastric intramucosal PCO2 as a quantitative indicator of the degree of acute
      hemorrhage.
AB  - PURPOSE: Gastric intramucosal PCO2 (PiCO2) is a marker of splanchnic dysoxia and
      hypoperfusion that is increasingly used in intensive care medicine. We assessed
      two methods, saline-balloon tonometry versus continuous capnometric recirculating
      gas tonometry (CRGT), for detecting changes in PiCO2 in animals subjected to
      various degrees of hemorrhage and examined whether changes in PiCO2 would
      correlate with the degree of hemorrhage as assessed by blood loss volume.
      MATERIALS AND METHODS: Following a baseline equilibration period, 20 anesthetized
      dogs were subjected to bleeding of 0, 23, 35, 41, or 47 mL/kg. After 30 minutes,
      the shed blood was reinfused and the experiments continued for an additional 120
      minutes. RESULTS: Aggregate baseline PiCO2 was 43 mm Hg by both methods. PiCO2
      did not change significantly over time in the control animals by either method.
      PiCO2 by CRGT rose significantly in each of the other groups at the end of the
      hemorrhage period and after resuscitation. Similar trends were observed in PiCO2
      measured by saline tonometry but were significant only with the most severe
      hemorrhage. Strong correlation was observed between the degree of hemorrhage and
      change in PiCO2 by both methods. CONCLUSION: PiCO2 serves as a quantitative
      indicator of the severity of hypovolemic perfusion failure associated with
      hemorrhage. Compared with standard saline tonometry, CRGT may be a more sensitive
      method of monitoring the severity of hemorrhage.

PMID- 9627271
TI  - Feasibility of noninvasive mechanical ventilation in the treatment of acute
      respiratory failure in postoperative cancer patients.
AB  - PURPOSE: Patients with cancer who require mechanical ventilation have high
      mortality rates. Although oncological patients have multiple clinical problems,
      including nutritional and immunological deficiencies, added complications from
      mechanical ventilation by themselves may be life-threatening and may further
      compromise the ability of these patients to recover from an episode of acute
      respiratory failure (ARF). Noninvasive mechanical ventilatory support (NIMV)
      using positive-pressure-ventilation delivered through a mask has gained
      popularity for the treatment of ARF and may limit some mechanical ventilation
      complications. The purpose of this study was to prospectively evaluate NIMV in
      cancer patients with ARF. MATERIALS AND METHODS: All patients admitted to the
      surgical intensive care unit (SICU) at The University of Texas M.D. Anderson
      Cancer Center from August 1, 1994, to April 15, 1996, with hypoxemic or
      hypercapnic ARF were eligible for this study. NIMV was delivered with the BiPAP
      S/T-D (Respironics, Murrysville, PA) device. The initial settings were adjusted
      to achieve a tidal volume of 5 to 7 mL/kg and a SaO2 greater than 0.90.
      Demographic data, duration of therapy, and need for endotracheal intubation were
      recorded for each patient. RESULTS: Sixty patients were included in this study.
      There were 21 women (35%) and 39 men. The primary cancer sites of these patients
      were gastrointestinal (25 patients), genitourinary (15), hematological (8), lung
      (6), sarcoma (4), and skin (2). Fifty-three patients (88%) had hypoxemic ARF and
      7 had hypercapnic ARF. The mean duration of NIMV was 1.83 days (range, 1 to 5
      days) with a median of 2 days. Forty-two patients (70%) were weaned from NIMV and
      were spared endotracheal intubation. The remaining 18 patients deteriorated and
      ultimately required intubation and assisted mechanical ventilation. No
      complications related to the use of NIMV were seen in this study population.
      CONCLUSIONS: NIMV was effective in the treatment of ARF in cancer patients at our
      institution substantially decreasing the need for intubation. This ventilatory
      technique is a viable option for cancer patients with ARF.

PMID- 9627272
TI  - Pulmonary stress injury within physiological ranges of airway and vascular
      pressures.
AB  - PURPOSE: The aim of this study was to assess the respective role of a small
      elevation in pulmonary capillary pressure, airway pressure, or both on alveolar
      capillary barrier permeability in an isolated perfused rat lung model. MATERIALS
      AND METHODS: Four groups were studied with low or high airway pressure (LA: 10
      mL/kg (tidal volume); HA: 20 mL/kg), low or high pulmonary artery pressure (LP: 9
      mm Hg; HP: 12 mm Hg): LALP, HALP, LAHP, and HAHP. The lungs were ventilated and
      perfused ex vivo for 30 minutes. Quantification of fluorescein isothiocyanate
      labeled (FITC) dextran in bronchoalveolar lavage (BAL) fluid and radiolabeled
      tracers assessed alveolar capillary barrier permeability. RESULTS: BALF FITC
      dextran was similar in the three groups with either one or two low-pressure
      parameters (LALP, LAHP, HALP), but high amounts were found in the HAHP group
      (375.2 x 10(-6) mg/mL v, respectively, 21.4, 26.2, and 30 x 10(-6) mg/mL, P =
      .0001). These results were consistent with the albumin space and extravascular
      lung water: higher values only in the HAHP group statistically different from the
      other groups (P < .002). Interalveolar pore examined with scanning electron
      microscopy showed an increase in diameters between LALP and HAHP (P < .0001).
      CONCLUSIONS: We can conclude that elevation of either the pulmonary artery
      pressure from 8 to 11 mm Hg or the alveolar pressure from 10 to 15 mm Hg alone
      does not change the permeability of the alveolar capillary membrane; however,
      there is an additive effect of these pressures.

PMID- 9627273
TI  - A comparison of mini-bronchoalveolar lavage and blind-protected specimen brush
      sampling in ventilated patients with suspected pneumonia.
AB  - PURPOSE: Mini-bronchoalveolar lavage (m-BAL) and blind-protected brush sampling
      (b-PSB) are minimally invasive methods of diagnosing pneumonia in mechanically
      ventilated patients. The aim of this study was to compare these techniques in a
      prospective study at a medical and surgical intensive care unit in a university
      affiliated community teaching hospital. PATIENTS AND METHODS: One hundred and
      ninety episodes of pneumonia was suspected in 175 mechanically ventilated
      patients. Sequential b-PSB followed by m-BAL were performed by respiratory
      therapists who had undergone specialized training. A b-PSB quantitative culture
      greater than 1,000 cfu/mL and a m-BAL greater than 10(4) cfu/mL was considered
      diagnostic of pneumonia. Colony counts between 500 and 1,000 cfu/mL and 5,000 -
      10(4) cfu/mL, respectively, were considered borderline positive. RESULTS: One
      hundred and ninety paired specimens were obtained from 175 patients. The
      diagnostic agreement between the two techniques was 90%. Sixty-six patients (37%)
      were considered to have bacterial pneumonia. In 108 episodes, patients were
      receiving concurrent antibiotics; pneumonia was diagnosed in 30 (27%) of these
      cases compared with 36 of 82 (43%) episodes off antibiotics (P = .03). In 6
      episodes, m-BAL was negative and b-PSB was positive (1 patient receiving
      antibiotics). In 13 episodes, b-PSB was negative and m-BAL was positive (7
      patients were receiving antibiotics). The b-PSB took 30 +/- 8 seconds to perform
      and was complicated by minor bleeding in 3 cases. The m-BAL took 5 +/- 2 minutes
      to perform, was considered easy in 105 cases, difficult/very difficult in 63, and
      failed in 2 patients. Significant coughing occurred in 98 patients with other
      minor reversible complications occurring in a further 20 cases. CONCLUSIONS: In
      mechanically ventilated patients with suspected pneumonia both b-PSB and m-BAL
      can be performed safely by respiratory therapists. The tests complement each
      other and likely reduce the number of false-negative results.

PMID- 9627274
TI  - Angiotensin converting enzyme inhibition has no effect on blood pressure and
      splanchnic perfusion after cardiac surgery.
AB  - PURPOSE: The purpose of this study was to study the effect of the angiotensin
      converting enzyme inhibitor, enalaprilat, on blood pressure and splanchnic
      perfusion after cardiac surgery. MATERIALS AND METHODS: Sixteen patients were
      studied after coronary artery bypass grafting. After admission to the intensive
      care unit, a 30-minute baseline measurement of systemic hemodynamics, oxygen
      transport, and gastric tonometry was performed. In 6 of 10 patients receiving
      enalaprilat and in each of 6 control patients, regional (splanchnic and leg)
      blood flows were measured also. After the baseline measurement period, 10
      patients received a 0.5 mg bolus of enalaprilat and thereafter an incremental
      infusion of enalaprilat up to a total dose of 10 mg (mean 8.3; range 4 to 10 mg)
      was continued to reduce the mean arterial pressure (MAP) to 70 to 80 mm Hg. A 30
      minute measurement period was repeated 2 to 3 hours after the first measurement
      period. In the control group, the second measurement was performed at
      corresponding time points. RESULTS: Though MAP decreased in the enalaprilat group
      (enalaprilat 99 +/- 14 mm Hg v 89 +/- 21 mm Hg, P < .05; control 95 +/- 13 mm Hg
      v82 +/- 10 mm Hg, P = NS) in only 4 of 10 patients was the targeted MAP reduction
      achieved. No significant changes were observed either in systemic or regional
      blood flows. Systemic, pulmonary, and femoral vascular resistance indices
      decreased significantly in both groups. Gastric-arterial PCO2 difference did not
      change in either groups. Angiotensin-converting enzyme activity decreased in the
      enalaprilat group (10.0 +/- 2.3 v 1.3 +/- 0.3 U x l(-1), P < .01), but plasma
      renin and endothelin-1 concentrations did not change in either group.
      CONCLUSIONS: The effect of enalaprilat on blood pressure was poor and it had no
      beneficial effects on splanchnic circulation. Renin-angiotensin activation is not
      a major factor in hypertension and splanchnic perfusion after cardiac surgery.

PMID- 9627275
TI  - The platelet-activating factor antagonist BB-882 does not improve tissue oxygen
      extraction in endotoxic shock.
AB  - PURPOSE: We investigated whether BB-882, a novel potent PAF antagonist, could
      influence systemic and pulmonary hemodynamics and oxygen extraction capabilities
      during an acute reduction in blood flow induced by cardiac tamponade after
      endotoxin challenge. MATERIALS AND METHODS: Twenty-one anesthetized, ventilated,
      and endotoxin-shocked (2 mg/kg i.v. Escherichia coli endotoxin) dogs were
      randomly divided in three groups. One group (N = 7) served as control. A second
      group (N = 7) received BB-882 as a single bolus dose of 5 mg/kg, 30 minutes
      before endotoxin administration. A third group (N = 7) received BB-882 as a
      continuous infusion of 5 mg/kg x h, started 30 minutes after endotoxin.
      Hemodynamic and gazometric measurements were obtained in all dogs 30 minutes
      after endotoxin injection and repeated 30 minutes after cardiac filling pressures
      were restored to baseline by generous saline infusion. Saline infusion rate was
      then set at 20 mL/kg x h and tamponade was induced by repeated bolus injections
      of warm saline into the pericardial sac. RESULTS: Compared with controls,
      pretreatment with BB-882 attenuated the early endotoxin-induced decrease in
      arterial pressure (70 +/- 17 v 51 +/- 14 mm Hg, P < .05), cardiac index (118 +/-
      29 v 91 +/- 15 mL/ kg x min, P < .05), stroke index (1.0 +/- 0.2 v 0.7 +/- 0.3
      mL/kg, P < .05), and left ventricular stroke work index (0.9 +/- 0.3 v 0.4 +/-
      0.2 g x m/kg, P < .05), but these effects were not sustained after fluid
      resuscitation. In contrast, BB-882 post-treatment maintained arterial pressure
      and improved cardiac performance at lower filling pressures in the later phase of
      endotoxic shock. BB-882 did not influence pulmonary hemodynamics. Treatment with
      BB-882 did not influence oxygen extraction at critical oxygen delivery (51.5 +/-
      9.9% and 52.8 +/- 13.9% v 46.6 +/- 9.0%, respectively BB-882 pretreatment and
      post-treatment v control). CONCLUSIONS: We conclude that in this model of
      endotoxic shock the administration of BB-882, either before or after endotoxin
      challenge, has time-related beneficial hemodynamic and cardiac effects but does
      not improve global oxygen extraction capabilities. The potential benefit of
      adjunctive treatment with a platelet-activating factor antagonist in sepsis
      remains doubtful.

PMID- 9627276
TI  - Clinical evaluation of the Abbott Qvue-OptiQ continuous cardiac output system in
      critically ill medical patients.
AB  - PURPOSE: The aim of this study was to evaluate the reliability of a new
      continuous cardiac output (CCO) monitoring device (Qvue/OptiQ system; Abbott
      Critical Care Systems, Mountain View, CA) based on the pulsed warm thermodilution
      technique in critically ill medical patients. METHODS: Nineteen patients with
      cardiogenic or septic shock were included in the study. Pairs of CCO and
      intermittent bolus cardiac output (ICO) were noted at least every 6 hours for
      determination of bias, precision, and limits of agreement. Simultaneously, blood
      samples were collected, and arterial-venous oxygen content difference (C[a-v]O2)
      was determined. A multiple stepwise logistic regression was used to identify
      situations associated with a CCO-ICO difference exceeded 20%. A multiple linear
      regression was performed to analyze the respective accuracy of CCO and ICO to
      predict the variations of C[a-v]O2. RESULTS: A total of 203 pairs of cardiac
      output measurements was obtained. The bias was 0.12 L/min (1.2% of pairs mean)
      and the precision 1.0 L/min (13%). The 95% limits of agreement were between -1.7
      L/min (-25%) and 1.9 L/min (+26%). Low blood temperatures and heart rates above
      120 beats/min were significantly associated with a ICO-CCO difference higher than
      20%. In a multiple linear regression, CCO was significantly correlated with C[a
      v]O2, an independent reflection of the patient's cardiac output; by contrast, ICO
      did not. CONCLUSION: These results suggest that ICO and CCO measurement by the
      Qvue/OptiQ system are interchangeable, except for temperature or heart rate
      extreme values.

PMID- 9627277
TI  - Prevalence and impact of chronic joint symptoms--seven states, 1996.
AB  - Arthritis and other rheumatic conditions are the leading cause of disability the
      United States, affecting 42.7 million persons and costing 65 billion dollars in
      1992. These numbers will increase by 2020 as the population ages. Few surveys
      exist to directly determine the prevalence and impact of arthritis at the state
      level. To address this gap, in 1995 state health departments and CDC developed a
      standardized, optional arthritis module for the Behavioral Risk Factor
      Surveillance System (BRFSS). This report summarizes results of the analyses of
      1996 data in seven states. The findings indicate that the prevalence and impact
      of "chronic joint symptoms"-- a proposed indicator for true arthritis and other
      rheumatic conditions -- is high and variable among states and that a large
      proportion of persons with arthritis diagnosed by a doctor do not know the type
      of arthritis they have.

PMID- 9627278
TI  - Community needs assessment and morbidity surveillance following an ice storm-
      Maine, January 1998.
AB  - On January 7,1998, an ice storm struck the northeastern United States and
      southeastern Canada. In Maine, 3 consecutive days of rain combined with ground
      temperatures consistently below freezing resulted in heavy accumulations of ice
      on trees and electric power lines. Falling trees and branches and breaking
      utility poles resulted in the loss of electrical power to an estimated 600,000
      persons. Although the rain had stopped by January 11, temperatures declined to <
      10 F (<-12 C) over most of the state, exacerbating the danger. On January 16, an
      estimated 50,000 households, primarily in the interior portion of the state,
      remained without power. This report summarizes a community needs assessment and a
      study of emergency department (ED) visits conducted during the aftermath of this
      storm.

PMID- 9627279
TI  - Boat-propeller-related injuries--Texas, 1997.
AB  - Approximately 78 million persons engage in recreational boating annually in the
      United States. Several types of injury can occur during boating recreation,
      including drowning, falls, burns, and propeller-related injuries. Injuries from
      the propeller are typically multiple, deep, parallel lacerations that can result
      in permanent scarring, substantial blood loss, traumatic or surgical amputation,
      or death. Persons sustaining injuries from boat propellers can require long
      periods of hospitalization, recovery, and rehabilitation. In Texas, the extent of
      boat-propeller-related injuries is unknown; however, the existence of
      approximately 600,000 motorboats in the state exposes many Texans to the
      potential risk for propeller-related injury. To characterize the occurrence of
      boat-propeller-related injuries in Texas, the Texas Department of Health (TDH)
      and the Texas Parks and Wildlife Department (TPWD) investigated boat-propeller
      related injuries that occurred in four lakes in Texas during May 24 -September 1,
      1997, the time of year when boating activities are most common. This report
      summarizes the results of the investigation.

PMID- 9627280
TI  - Understanding the genes involved in spermatogenesis: a progress report.
AB  - OBJECTIVE: To review the current literature on genes known to affect fertility in
      the human and mouse. DESIGN: A literature review was performed and key articles
      were chosen for focus in the areas of genes with effects only on spermatogenesis
      and oogenesis, with an emphasis on Y-chromosome-encoded gene families and
      spermatogenesis. In addition, studies describing genes deleted in transgenic mice
      were incorporated. RESULT(S): Several gene families on the Y chromosome are
      implicated in spermatogenic failure, but the link between the genetic lesion and
      the resulting defect is unclear. Many mouse genes involved in repair and DNA
      damage monitoring have specific effects on gametogenesis in and around meiosis.
      CONCLUSION(S): Many genes are involved only in gametogenesis, and some of these
      are beginning to be understood in terms of their functions. An even larger number
      of genes is required for gametogenesis, and other functions and mouse models give
      insights important for human disease.

PMID- 9627281
TI  - Ovarian tissue banking in patients with Hodgkin's disease: is it safe?

PMID- 9627282
TI  - Ovarian tissue cryopreservation: the time is now. Transplantation or in vitro
      maturation: the time awaits.

PMID- 9627283
TI  - Young low responders protected from untoward effects of reduced ovarian response.
AB  - OBJECTIVE(S): To correlate fertilization and clinical pregnancy rates (PRs) in
      low responders with their E2 levels (<500, 500-800, >800-1,000 pg/mL), age (20
      30, 31-40, >40 years), number of follicles, and number of oocytes retrieved.
      DESIGN: A retrospective study. SETTING: The IVF unit of an academic hospital.
      PATIENT(S): One hundred forty-three women who failed to attain E2 levels of 1,000
      pg/mL on the day of hCG administration. INTERVENTION(S): Controlled ovarian
      hyperstimulation, blood E2 and progesterone measurements, ultrasonographic
      scanning of ovarian follicles, oocyte retrieval after hCG administration, and ET.
      MAIN OUTCOME MEASURE: Clinical PR. RESULT(S): Although E2 levels, fertilization
      rates, age, and number of oocytes did not differ significantly between the three
      age groups, the PR achieved in the youngest group was approximately three times
      as high (19.3%) as that achieved in the two older groups. CONCLUSION: Young low
      responders represent a unique subset in that their age protects them from the
      deleterious effects of poor ovarian response.

PMID- 9627284
TI  - Success rate with repeated cycles of in vitro fertilization-embryo transfer.
AB  - OBJECTIVE: To analyze data from a large multicenter study to determine whether
      pregnancy and delivery rates decrease with repeated IVF-ET cycles. DESIGN:
      Multicenter retrospective study. SETTING: Participating centers from the Society
      of Assisted Reproductive Technology. PATIENT(S): Fifty-four centers contributed
      4,043 cycles of oocyte retrieval for uterine transfer. INTERVENTION(S): Oocyte
      retrieval for uterine transfer. MAIN OUTCOME MEASURE(S): Pregnancy and delivery
      rates, analyzed according to age, program success rate, and whether the program
      was doing assisted hatching. RESULT(S): Pregnancy and delivery rates for cycles
      1, 2, 3, 4, and >4 were 33.7% and 27.0%, 33.9% and 27.4%, 28.9% and 23.4%. 25.9%
      and 16.1%, and 21.0% and 15.4%, respectively. The pregnancy rate decreased
      significantly for >4 cycle; delivery rate decreased significantly for cycles 4
      and >4. Assisted hatching was strongly related to better odds of pregnancy (OR,
      1.50) and delivery (OR, 1.44) in women under age 40, and for pregnancy (1.64) in
      women age 40-42 years. CONCLUSION(S): Success rates do not decrease markedly with
      repeated IVF attempts, and the decrease did not change with program success rate,
      suggesting the IVF population is not markedly heterogeneous. Uncontrolled studies
      of new treatments for cycle repeaters cannot assume that success rate is poor
      without a treatment change.

PMID- 9627285
TI  - Elevated levels of basal estradiol-17beta predict poor response in patients with
      normal basal levels of follicle-stimulating hormone undergoing in vitro
      fertilization.
AB  - OBJECTIVE: To evaluate whether the predictive ability of a normal FSH level on
      cycle day 3 can be enhanced by levels of estradiol-17beta (E2) on cycle day 3.
      DESIGN: Prospective cohort study. SETTING: University hospital-based, tertiary
      care infertility center. PATIENT(S): Two hundred thirty-one consecutively seen
      patients who attended the center for their first IVF attempt. INTERVENTION(S):
      Blood samples were collected on day 3 of the cycle preceding IVF; IVF was
      performed in all patients. MAIN OUTCOME MEASURE(S): Patient's age, number of
      ampules of hMG, cancellation rate, number of oocytes, fertilization rate, and
      clinical pregnancy rate. RESULT(S): In patients with elevated FSH levels on cycle
      day 3, a low oocyte yield was achieved (7 versus 11) and a high number of ampules
      of hMG was necessary (56 versus 33). Their cancellation rate was high (67% versus
      16%). In patients with normal basal FSH levels, high E2 levels predicted a high
      cancellation rate (56%, versus 13% in patients with low E2 levels) and a low
      oocyte yield (9, versus 11 in patients with low E2 levels). Patients with both
      normal FSH levels and low E2 levels on cycle day 3 fared best. CONCLUSION(S): The
      basal E2 level on cycle day 3 is a useful prognosticator of response to
      stimulation in IVF patients with normal basal FSH levels.

PMID- 9627286
TI  - Day 4 estradiol levels predict pregnancy success in women undergoing controlled
      ovarian hyperstimulation for IVF.
AB  - OBJECTIVE: To evaluate the usefulness of serum estradiol levels obtained on the
      fourth day of gonadotropin stimulation in predicting the likelihood of pregnancy
      during controlled ovarian hyperstimulation (COH) using luteal phase leuprolide
      acetate (LA). DESIGN: A 4-year retrospective analysis of day 4 estradiol levels
      and subsequent clinical pregnancy and delivery rates. SETTING: A university
      hospital tertiary referral center. PATIENT(S): Couples undergoing IVF treatment.
      MAIN OUTCOME MEASURE(S): Primary outcome measures included clinical pregnancy and
      delivery rates. Secondary outcome measures included the number of oocytes
      retrieved and the number of embryos available for transfer per COH cycle.
      RESULT(S): The clinical pregnancy and delivery rates for cycles with day 4
      estradiol levels of >75 pg/mL were 42.3% (30/71) and 32.4% (23/71), respectively.
      These rates differed significantly from those for cycles with day 4 estradiol
      levels of < or = 75 pg/mL, which were only 9.1% (4/44) and 6.8% (3/44),
      respectively. The number of oocytes retrieved and the number of embryos available
      for transfer for cycles with day 4 estradiol levels of >75 pg/mL also differed
      significantly from those for cycles with day 4 estradiol levels of < or = 75
      pg/mL (11.4 and 7.8 versus 6.8 and 4.3, respectively). CONCLUSION(S): Estradiol
      levels obtained on the fourth day of gonadotropin therapy are highly predictive
      of successful ovulation induction and pregnancy outcome in cycles using luteal
      phase LA.

PMID- 9627287
TI  - Does previous salpingectomy improve implantation and pregnancy rates in patients
      with severe tubal factor infertility who are undergoing in vitro fertilization? A
      pilot prospective randomized study.
AB  - OBJECTIVE: To evaluate the implantation rate and pregnancy rate (PR) in patients
      with severe tubal factor infertility who were undergoing IVF. Patients who had
      undergone salpingectomy were compared with those who had not. DESIGN: A
      prospective randomized study. SETTING: A department of obstetrics and gynecology
      at a university hospital. PATIENT(S): Thirty patients who previously had
      undergone salpingectomy and 30 patients who had not undergone salpingectomy
      before IVF treatment. INTERVENTION(S): Laparoscopy with or without salpingectomy
      followed by IVF with the use of combined GnRH agonist and hMG therapy in a long
      stimulation protocol. MAIN OUTCOME MEASURE(S): Embryo implantation rate and
      ongoing PR per transfer. The cumulative PRs were compared for the two groups of
      patients. RESULT(S): After the first IVF attempt, the implantation rate was 10.4%
      in the group with salpingectomy and 4.6% in the group without salpingectomy. For
      all IVF attempts, the respective embryo implantation rates in the two groups were
      13.4% and 8.6%. The ongoing PR per transfer was 34.2% in the group with
      salpingectomy compared with 18.7% in the group without salpingectomy. After four
      IVF attempts, the probability of becoming pregnant was greater in the group of
      patients with salpingectomy (75%) than in the group without salpingectomy (63%).
      CONCLUSION(S): Previous salpingectomy in patients with severe tubal factor
      infertility who are undergoing IVF seems to increase the embryo implantation rate
      and the PR per cycle of IVF. This monocentric study must be followed by other
      similar studies to allow for a metaanalysis and confirm this clear trend with
      definitive evidence.

PMID- 9627288
TI  - Coping style and depression level influence outcome in in vitro fertilization.
AB  - OBJECTIVE: To examine the influence of depression levels and coping on IVF
      outcome in women, taking into account the cause of infertility. DESIGN:
      Prospective clinical study. SETTING: A university hospital. PATIENT(S): Ninety
      eight women undergoing IVF treatment. INTERVENTION(S): Psychometric tests were
      administered at the first visit (day 3) of the investigated treatment cycle. MAIN
      OUTCOME MEASURE(S): Achievement of pregnancy. RESULTS: The nonpregnant group
      reported increased expression of negative emotions. In the subgroup with a female
      indication for IVF, increased depressive symptomatology (correlated with
      increased expression of negative emotions) was associated with lower pregnancy
      rates (PRs), whereas in the subgroup with a male indication for IVF, increased
      depressive symptomatology (correlated with decreased expression of negative
      emotions) was associated with higher PRs. CONCLUSION(S): Expression of negative
      emotions predicts depression levels and outcome in IVF. The cause of infertility
      should be taken into account when investigating the relation between psychologic
      functioning and outcome in IVF.

PMID- 9627289
TI  - Fecundity of infertile women with minimal or mild endometriosis and women with
      unexplained infertility. The Canadian Collaborative Group on Endometriosis.
AB  - OBJECTIVE: To assess whether infertile women with minimal or mild endometriosis
      have lower fecundity than women with unexplained infertility. DESIGN: Prospective
      cohort study. SETTING: Twenty-three infertility clinics across Canada.
      PATIENT(S): Three hundred thirty-one infertile women aged 20-39 years.
      INTERVENTION(S): Diagnostic laparoscopy for infertility. Infertile women with
      minimal or mild endometriosis (n = 168) were compared with women with unexplained
      infertility (n = 263). Both groups were managed expectantly. The women were
      followed up for 36 weeks after the laparoscopy or, for those who became pregnant,
      for up to 20 weeks of the pregnancy. MAIN OUTCOME MEASURE(S): Fecundity refers to
      the probability of becoming pregnant in the first 36 weeks after laparoscopy and
      carrying the pregnancy for > or = 20 weeks. The fecundity rate is the number of
      pregnancies per 100 person-months. RESULT(S): Fecundity was 18.2% in infertile
      women with minimal or mild endometriosis and 23.7% in women without endometriosis
      (log-rank test). The fecundity rate was 2.52 per 100 person-months in women with
      endometriosis and 3.48 per 100 person-months in women with unexplained
      infertility. The crude and adjusted fecundity rate ratios were 0.72 and 0.83 (95%
      confidence interval = 0.53-1.32), respectively. CONCLUSION(S): The fecundity of
      infertile women with minimal or mild endometriosis is not significantly lower
      than that of women with unexplained infertility.

PMID- 9627290
TI  - Spontaneous apoptosis of endometrial tissue is impaired in women with
      endometriosis.
AB  - OBJECTIVE: To evaluate spontaneous apoptosis in single-cell suspensions of
      eutopic and ectopic endometrium from women with endometriosis and in eutopic
      endometrium from fertile controls without endometriosis. DESIGN: Paired specimens
      of eutopic and ectopic endometrial tissue from patients with endometriosis and
      eutopic endometrium from controls were assessed for spontaneous apoptosis.
      SETTING: Institute for the Study and Treatment of Endometriosis and university
      based research laboratories. PATIENT(S): Fertile controls (n = 10) and women with
      untreated endometriosis (n = 16). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):
      Spontaneous apoptosis assessed with an ELISA-based cell death detection kit.
      RESULT(S): Spontaneous apoptosis (monitored by absorbance) of eutopic endometrium
      from patients with endometriosis and fertile controls was 0.63 +/- 0.1 and 1.43
      +/- 0.11, respectively. Among patients with endometriosis, spontaneous apoptosis
      of ectopic endometrium was 0.26 +/- 0.06. Decreased apoptosis of ectopic versus
      eutopic endometrium was observed independent of cycle phase. CONCLUSION(S): The
      susceptibility of endometrial tissue to spontaneous apoptosis is significantly
      lower in women with endometriosis than in fertile controls. We suggest that
      decreased susceptibility of endometrial tissue to apoptosis contributes to the
      etiology or pathogenesis of endometriosis.

PMID- 9627291
TI  - Laparoscopic surgical management of diaphragmatic endometriosis.
AB  - OBJECTIVE: To review the clinical presentations of and management options for
      diaphragmatic endometriosis. DESIGN: Retrospective review. SETTING: Referral
      center. PATIENT(S): Twenty-four women with endometriosis of the diaphragm.
      INTERVENTION(S): Surgical management. MAIN OUTCOME MEASURE(S): Diagnostic
      accuracy and therapeutic feasibility of operative laparoscopy. RESULT(S):
      Operative findings in 17 patients included 2-5 spots of endometriosis on the
      diaphragm measuring <1 cm. Seven women had numerous lesions scattered across the
      diaphragm. Lesions were bilateral in 8 patients, limited to the right
      hemidiaphragm in 14 patients, and limited to the left hemidiaphragm in 2
      patients. In 7 patients, six endometriosis lesions were directly in the line of
      the left ventricle and three lesions were adjacent to the phrenic nerve.
      Endometriosis was infiltrating into the muscular layer of the diaphragm in 7
      patients. The symptoms in all 7 symptomatic patients decreased significantly
      after treatment, with a minimum follow-up period of 12 months. No postoperative
      complications occurred. CONCLUSION(S): The abdominal diaphragm can be involved
      with endometriosis and can be diagnosed and treated effectively with the use of
      videolaparoscopy.

PMID- 9627292
TI  - Goserelin acetate (Zoladex) with or without hormone replacement therapy for the
      treatment of endometriosis.
AB  - OBJECTIVE: To determine whether hormone replacement therapy (HRT) plus goserelin
      (Zoladex) is as effective as goserelin alone for the relief of pelvic symptoms of
      endometriosis and to determine whether it reduces both the loss of bone mineral
      density (BMD) and the physiologic side effects associated with goserelin therapy.
      DESIGN: Prospective, placebo-controlled study, open label for goserelin therapy
      and double-blind for HRT. SETTING: Forty-two teaching or community hospitals.
      PATIENT(S): Premenopausal women with symptomatic endometriosis. RESULT(S):
      Statistically significant mean decreases from baseline in the total pelvic
      symptom score and total subjective score were observed by week 24 for all three
      groups. There were no statistically significant treatment differences for change
      in total symptom score. Some degree of BMD loss occurred in the three groups;
      however, the percentage loss was consistently greater in the HRT0 group than in
      the HRT1 or HRT2 groups. When analyzed separately, no overall age effect on BMD
      change was seen in women >30 years of age versus women < or = 30 years. The HRT1
      and HRT2 groups had fewer occurrences of hot flushes and vaginal dryness than did
      the HRT0 group. CONCLUSION(S): Goserelin plus HRT is as effective as goserelin
      alone in relieving pelvic symptoms of endometriosis and attenuates both the loss
      of BMD and the physiologic side effects of hot flushes and vaginal dryness
      associated with goserelin therapy.

PMID- 9627293
TI  - Why do women choose endometrial ablation rather than hysterectomy?
AB  - OBJECTIVE: To determine why women choose endometrial ablation rather than
      hysterectomy for the treatment of menorrhagia. DESIGN: Observational study based
      on postal questionnaires. SETTING: A university hospital. PATIENT(S): One hundred
      eighty randomly selected patients from a cohort of 658 patients who underwent
      endometrial ablation for the treatment of menorrhagia during the past 7 years.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Patient attitude about
      endometrial ablation. RESULT(S): One hundred six questionnaires (58.9%) were
      completed satisfactorily. The average postoperative follow-up period was 45.1
      months (range, 3-80 months). Eleven women (10.4%) had undergone repeated
      endometrial ablation and 8 (7.5%) had undergone hysterectomy. More than half the
      women indicated that they would find endometrial ablation acceptable even if
      there was no chance of amenorrhea, if the probability of menstruation becoming
      lighter was > or = 4:10, if the likelihood of menstrual pain decreasing was > or
      = 3:10, if the chance of requiring repeated endometrial ablation or hysterectomy
      was < or = 1:4, and if the risk of uterine cancer after surgery was < or = 1:200.
      The three most important advantages of endometrial ablation over hysterectomy
      were perceived to be the avoidance of major surgery, the fast return to normal
      functioning, and the short hospitalization. CONCLUSION(S): Most women who choose
      endometrial ablation rather than hysterectomy as therapy for menorrhagia are
      prepared to undergo hysteroscopic surgery even if the chance of success is
      relatively poor.

PMID- 9627294
TI  - Reduction of de novo postsurgical adhesions by intraoperative precoating with
      Sepracoat (HAL-C) solution: a prospective, randomized, blinded, placebo
      controlled multicenter study. The Sepracoat Adhesion Study Group.
AB  - OBJECTIVE: To assess the efficacy and safety of Sepracoat (HAL-C; Genzyme
      Corporation, Cambridge, MA) solution in reducing the incidence, severity, and
      extent of de novo adhesion formation at sites without direct surgical trauma or
      adhesiolysis at the time of gynecologic laparotomy. DESIGN: Prospective,
      randomized, blinded, placebo-controlled multicenter study. Patients underwent
      gynecologic procedures via laparotomy; approximately 40 days later, surgeons
      assessed their adhesions during second-look laparoscopy. SETTING: Twenty-three
      North American institutions. PATIENT(S): Two hundred seventy-seven women for
      safety evaluations; 245 women for efficacy studies. INTERVENTION(S):
      Intraoperative serosal coating with Sepracoat (treatment) or phosphate-buffered
      saline (placebo) after opening of the abdominal cavity, after irrigation or every
      30 minutes during surgery, and at the completion of surgery. MAIN OUTCOME
      MEASURE(S): Incidence, severity, and extent of de novo adhesions to 23
      intraabdominal sites. RESULT(S): The Sepracoat group had a significantly lower
      incidence of de novo adhesions than the placebo group as assessed by the
      proportion of sites involved (0.23 +/- 0.02 versus 0.30 +/- 0.02, respectively)
      and the percentage of patients without de novo adhesions (13.1% versus 4.6%,
      respectively), as well as significantly reduced adhesion extent and severity.
      Sepracoat was well tolerated, with a safety profile nearly identical to that of
      the placebo. CONCLUSION(S): Sepracoat was significantly more effective than
      placebo and was safe in reducing the incidence, extent, and severity of de novo
      adhesions to multiple sites indirectly traumatized by gynecologic surgery via
      laparotomy.

PMID- 9627295
TI  - The addition of dexamethasone to antiandrogen therapy for hirsutism prolongs the
      duration of remission.
AB  - OBJECTIVE: To determine whether the addition of dexamethasone to antiandrogen
      therapy prolongs the duration of remission in women with hirsutism. DESIGN:
      Follow-up study of patients treated with one of four regimens: spironolactone
      (100 mg/d) for 1 year, dexamethasone (0.37 mg/d) for 1 year, dexamethasone (0.37
      mg/d) plus spironolactone (100 mg/d) for 1 year, or dexamethasone (0.37 mg/d)
      plus spironolactone (100 mg/d) for 2 years. SETTING: Academic medical practice in
      reproductive endocrinology. PATIENT(S): Fifty-four women with hirsutism and
      hyperandrogenism. INTERVENTION(S): Ferriman-Gallwey-Lorenzo scores were obtained
      and serum levels of testosterone, unbound testosterone, and
      dehydroepiandrosterone sulfate were measured before therapy, every 6 months
      during therapy, and for 1 year after the withdrawal of therapy. MAIN OUTCOME
      MEASURE(S): Hirsutism scores and serum indices of hormonal changes were
      monitored. RESULT(S): Ferriman-Gallwey-Lorenzo scores and androgen levels
      remained low 1 year after the withdrawal of therapy in patients who were treated
      with dexamethasone, either alone or in combination with spironolactone. In
      patients who were treated with spironolactone alone, hirsutism scores had
      returned to baseline values after 1 year. CONCLUSION(S): The addition of an agent
      that suppresses androgen levels may be useful to prolong the duration of
      remission of hirsutism in women with hyperandrogenism who are treated with
      antiandrogens.

PMID- 9627296
TI  - Outcome of in vitro fertilization and intracytoplasmic injection of epididymal
      and testicular sperm extracted from patients with obstructive and nonobstructive
      azoospermia.
AB  - OBJECTIVE: To evaluate IVF outcome after epididymal and testicular sperm
      retrieval in patients with obstructive or nonobstructive azoospermia. DESIGN:
      Retrospective clinical analysis. SETTING: Public university-affiliated IVF unit.
      PATIENT(S): One hundred twenty-three azoospermic patients (178 cycles).
      INTERVENTION(S): Sixty-three patients (103 cycles) with obstructive azoospermia
      (group 1) underwent either epididymal or testicular sperm retrieval, and 60
      patients (75 cycles) with nonobstructive azoospermia (group 2) underwent
      testicular sperm retrieval combined with IVF treatment. Mature oocytes were
      fertilized using intracytoplasmic sperm injection. After sperm preparation,
      supernumerary spermatozoa were cryopreserved. MAIN OUTCOME MEASURE(S): Oocyte
      fertilization rate and clinical pregnancy rate (PR). RESULT(S): The oocyte
      fertilization rate was 48.4% (534/1,104) in group 1 and 41.5% (312/751) in group
      2 (not significant [NS] difference). A total of 100 cycles (97.1%) and 62 cycles
      (82.7%) in the obstructive and nonobstructive groups, respectively, had embryos
      for replacement (NS difference). The clinical PRs per ET cycle were 24% (24/100)
      and 17.7% (11/62) in the two groups, respectively. Oocyte fertilization rates,
      when fresh (46.4%) or frozen-thawed (41.8%) spermatozoa were used, were not
      significantly different in the two groups. The PR when fresh sperm were used was
      23.6% (30/127), versus 14.3% (5/35) when frozen sperm were used (NS difference).
      The PR for women aged < or = 35 years was similar to that for women >35 years of
      age (20.7% or 29/140 and 18.2% or 4/25, respectively). CONCLUSION(S): Epididymal
      and testicular sperm obtained in azoospermic patients can fertilize oocytes
      successfully and may lead to high fertilization rates and PRs. Freezing of these
      spermatozoa does not reduce the outcome of treatment significantly.

PMID- 9627298
TI  - Evidence for oxidatively modified lipid-protein complexes in endometrium and
      endometriosis.
AB  - OBJECTIVE: To evaluate for the presence of oxidatively modified lipid-protein
      complexes in endometriosis and endometrium of women with endometriosis and
      controls. DESIGN: Controlled clinical study. SETTING: Academic tertiary care
      center. PATIENT(S): Women undergoing surgery for pelvic pain, infertility,
      endometriosis, or tubal ligation controls. INTERVENTION(S): Biopsy of endometrium
      and endometriosis. MAIN OUTCOME MEASURE(S): Staining with antibodies to
      oxidatively modified lipid proteins (HNE-7, MDA2), macrophages (HAM-56), and
      muscle cell actin (HHF-35). RESULT(S): Both endometrium and endometriosis tissues
      contain stromal cells that immunostain with HAM-56 and show immunostaining (both
      intracellular and extracellular) with HNE-7 and MDA2. Some endometriotic implants
      show patchy staining with HHF-35. Endometrium was devoid of staining with HHF-35.
      Control staining with nonimmune sera in both tissues was also devoid of staining.
      CONCLUSION(S): These data strongly implicate the occurrence of oxidative stress
      in endometriosis tissue. These data also suggest that oxidative modification is a
      normal physiological process in endometrium.

PMID- 9627297
TI  - Macrophage scavenger receptor(s) and oxidatively modified proteins in
      endometriosis.
AB  - OBJECTIVE: To determine whether cultured human peritoneal macrophages have
      functional scavenger receptor(s) and whether activation of macrophages in
      endometriosis may involve an increase in scavenger receptor activity. DESIGN: A
      controlled clinical study comparing peritoneal fluid (PF) macrophages of women
      with endometriosis and controls without endometriosis. SETTING: Women undergoing
      laparoscopic evaluation and treatment in a tertiary medical center. PATIENT(S):
      Twenty-one women undergoing evaluation for pelvic pain or infertility and 10
      women undergoing elective laparoscopic tubal ligation. INTERVENTION(S): None.
      MAIN OUTCOME MEASURE(S): Evidence for functional macrophage scavenger receptor
      and evidence of ligands for the scavenger receptor in PF. RESULT(S): Peritoneal
      macrophages of women with endometriosis degrade significantly more endothelial
      cell-low density lipoprotein (EC-LDL) and copper-oxidized LDL (Cu-LDL) than
      native LDL. Macrophages of women with endometriosis also incorporate more labeled
      oleic acid into cholesteryl ester in the presence of oxidized LDL (Ox-LDL) than
      in the presence of native LDL. Western blot analysis demonstrates the presence of
      adducts between lipid peroxidation products and proteins in PF of patients with
      and without endometriosis. The PF of women with endometriosis competes with
      labeled Ox-LDL for uptake by mouse peritoneal macrophages in a dose-dependent
      manner. CONCLUSION(S): We demonstrate for the first time that human macrophages
      have functional scavenger receptor(s) and that activation of macrophages in
      endometriosis involves an increase in scavenger receptor activity. Two lines of
      evidence indicate the presence of ligands for the scavenger receptor in PF.

PMID- 9627299
TI  - Expression and hormonal regulation of monocyte chemotactic protein-1 in
      myometrium and leiomyomata.
AB  - OBJECTIVE: The pathogenesis of leiomyoma likely involves interactions of sex
      steroids with paracrine growth factors or cytokines resulting in modulation of
      local immunity. Monocyte chemotactic protein-1 (MCP-1) is a chemotactic and
      activating factor for monocytes and is produced by multiple tumors and has
      antitumor effects. We investigated the expression of MCP-I in leiomyoma and
      myometrium as well as the regulatory role of steroid hormones and cytokines on
      MCP-1 expression and the effect of MCP-1 on the proliferation of leiomyoma cells.
      DESIGN: Prospective study. SETTING: University medical center. PATIENT(S): Women
      with (n = 20) or without (n = 11) leiomyoma. INTERVENTION(S): First. MCP-1
      messenger RNA (mRNA) levels in myometrium and leiomyoma were measured, and then
      myometrial and leiomyoma cells in culture were treated with steroid hormones and
      cytokines. MAIN OUTCOME MEASURE(S): The MCP-1 mRNA was evaluated by Northern
      analysis. Immunoreactive MCP-1 in cell cultures was quantified by ELISA.
      Leiomyoma cell proliferation was assessed with [3H]thymidine incorporation.
      RESULT(S): The MCP-1 mRNA levels in myometrial samples were 4.7-fold higher than
      in the leiomyoma samples. Myometrial MCP-1 mRNA levels were 2.4-fold higher in
      secretory than in proliferative phase samples. The highest MCP-1 levels were
      observed in samples from women using GnRH analogues. Estradiol and progestins,
      alone or in combination, resulted in a decrease in MCP-1 protein production.
      There was an increase in the proliferation of leiomyoma cells treated with anti
      MCP-1 neutralizing antibody. CONCLUSION(S): These findings suggest that MCP-1 may
      have antineoplastic activity in leiomyomata and that sex steroids may be exerting
      their growth stimulatory effect in leiomyomata through down-regulation of MCP-1.

PMID- 9627300
TI  - Cytolysis of eutopic and ectopic endometrial cells by peripheral blood monocytes
      and peritoneal macrophages in women with endometriosis.
AB  - OBJECTIVE: To compare the ability of peripheral blood monocytes (PBM) and
      peritoneal macrophages (PM) to mediate the in vitro cytolysis of endometrial
      cells from eutopic and ectopic endometrium in women with endometriosis. DESIGN:
      Prospective study of immune function. SETTING: Institute for the Study and
      Treatment of Endometriosis and university-based research laboratories.
      PATIENT(S): Twenty-four women with endometriosis (15 in stage I/II, 9 in stage
      III/IV) and 4 patients treated with GnRH agonists. INTERVENTION(S): Peritoneal
      fluid and peripheral blood were sampled and eutopic and ectopic endometrium were
      biopsied during diagnostic laparoscopy. MAIN OUTCOME MEASURE(S): Lysis of
      autologous endometrial cells. RESULT(S): Peripheral blood monocytes were
      significantly more cytolytic than peritoneal macrophages against autologous
      uterine endometrial cells. However, PBM and PM displayed a similar degree of
      cytolysis against a hepatoma cell line. Ectopic endometrial cells were
      significantly more resistant to cytolysis by autologous PBMC than were matched
      eutopic endometrial cells, and were completely resistant to cytolysis by
      autologous PM. CONCLUSION(S): The reduced capacity of PM from women with
      endometriosis to mediate the destruction of endometrial cells coupled with the
      increased resistance of ectopic endometrial cells to macrophage-mediated
      cytolysis may facilitate the survival of these cells within the peritoneal cavity
      of women with endometriosis.

PMID- 9627301
TI  - Use of clomiphene citrate in the treatment of men with high sperm chromatin
      stability.
AB  - OBJECTIVE: To determine whether improvements of the seminal vesicle function
      after a 5-day course with clomiphene citrate (CC) may reduce the prevalence of
      men with high sperm chromatin stability under conditions of sodium dodecyl
      sulfate (SDS)-ethylenediaminetetraacetic acid (EDTA). DESIGN: A prospective
      study. SETTING: Andrology laboratory at the Instituto de Investigaciones de la
      Altura, Universidad Peruana Cayetano Heredia, Lima, Peru. PATIENT(S): Forty-one
      male partners of infertile couples attending the andrology laboratory.
      INTERVENTION(S): Clomiphene citrate was administered orally twice a day. Men were
      treated with CC at 100 mg daily for 5 days. Blood and semen samples were
      collected before treatment and 24 hours after the last administration. MAIN
      OUTCOME MEASURE(S): Serum testosterone, seminal fructose, sperm motility, sperm
      chromatin stability after SDS and EDTA, and prevalence of high sperm chromatin
      stability. RESULT(S): The percentage of stable sperm after SDS-EDTA correlated
      inversely with the basal corrected concentration of seminal fructose (-1.77 +/-
      0.89, beta +/- SE). High sperm chromatin stability was observed in 53.8% of the
      study population and in 66.7% of patients with hypofunction of the seminal
      vesicles. In those men whose seminal vesicle function improved after treatment
      with CC, the prevalence of high sperm chromatin stability was reduced from 67% to
      25% (chi2 = 5.34). Logistic regression analysis showed that the higher the basal
      corrected seminal fructose levels and the higher the basal serum testosterone
      levels, the lower the probability of nonresponse of the sperm chromatin stability
      to treatment with CC (0.54 +/- 0.15, odds ratio +/- SE for corrected fructose;
      and 0.50 +/- 0.15, odds ratio +/- SE for serum testosterone). CONCLUSION(S):
      Hypofunction of the seminal vesicles was associated with high sperm chromatin
      stability, and this high sperm chromatin stability under SDS-EDTA conditions may
      be reduced by treatment with CC.

PMID- 9627302
TI  - Regional distribution of 5alpha-reductase type 1 and type 2 mRNA along the human
      epididymis.
AB  - OBJECTIVE: To determine the regional distribution and relative expression of
      5alpha-reductase type 1 and type 2 mRNA within the human testis and regions of
      the epididymis. DESIGN: Prospective observational study. SETTING: University
      academic medical center. PATIENT(S): Two young adult male organ donors.
      INTERVENTION(S): None MAIN OUTCOME MEASURE(S): The distribution of 5alpha
      reductase type 1 and type 2 mRNA in the testis and regions of the epididymis was
      detected by Northern blot analysis. The relative abundance of each 5alpha
      reductase mRNA was evaluated using semiquantitative reverse transcriptase
      polymerase chain reaction (RT-PCR) in which cyclophilin mRNA, a house-keeping
      gene product, was coamplified as the reference standard. RESULT(S): Northern blot
      analysis revealed the 5alpha-reductase type 2 transcript in the midcaput, distal
      caput, corpus, and proximal cauda of the epididymis, but the transcript was
      undetectable in the testis, proximal caput, and distal cauda region. No
      transcript for the type 1 isozyme was detected by Northern blot. The more
      sensitive RT-PCR showed low levels of type 1 mRNA in the testis and epididymis,
      with the highest abundance in the proximal caput. Type 2 mRNA of 5alpha-reductase
      was most abundant in the midcaput, was decreased in the more distal regions, and
      was more abundant than type 1 mRNA in all epididymal regions except for the
      proximal caput. CONCLUSION(S): Both 5alpha-reductase type 1 and type 2 mRNAs are
      present in the human epididymis. The type 2 isozyme mRNA is predominant, being
      more highly expressed than the low-abundance type 1 mRNA.

PMID- 9627303
TI  - Interindividual variations in the disomy frequencies of human spermatozoa and
      their correlation with nuclear maturity as evaluated by aniline blue staining.
AB  - OBJECTIVE: To evaluate the importance of interindividual variations in the disomy
      frequencies of human sperm and their possible correlation with the principal
      semen parameters. DESIGN: Prospective randomized analysis of sperm nuclei by
      fluorescence in situ hybridization and analysis of semen parameters. SETTING:
      University-based laboratory for reproductive biology. PATIENT(S): Fifty-seven
      human ejaculates selected at random from a population of men undergoing semen
      analysis. INTERVENTION(S): Semen specimens were analyzed, and sperm samples were
      prepared for fluorescence in situ hybridization. MAIN OUTCOME MEASURE(S): Semen
      parameters, including necrozoospermia, global motility, sperm concentration,
      multiple abnormalities index, and teratozoospermia were evaluated, aniline blue
      staining was completed, and disomy frequencies for chromosomes 8, 15, 18, X, and
      Y were determined using fluorescence in situ hybridization. RESULT(S): Noticeable
      differences in disomy frequencies between individuals were observed, and these
      frequencies were correlated with the degree of nuclear maturity. CONCLUSION(S):
      We hypothesize that the positive correlation can be explained by an abnormality
      of chromosomal segregation at the time of meiosis that would cause disturbances
      during the transition of nucleoprotein or by one or several premeiotic
      abnormalities of chromatin that would perturb both the meiotic process and the
      construction of definitive proteins.

PMID- 9627304
TI  - Tissue inhibitor of metalloproteinase-1 concentrations are attenuated in
      peritoneal fluid and sera of women with endometriosis and restored in sera by
      gonadotropin-releasing hormone agonist therapy.
AB  - OBJECTIVE: To establish tissue inhibitor of metalloproteinase-1 (TIMP-1)
      concentrations in peritoneal fluid (PF) and sera of women with endometriosis and
      compare them to disease-free controls. DESIGN: Prospective randomized study.
      SETTING: Academic medical center. PATIENT(S): Women with laparoscopically
      documented endometriosis and disease-free women of reproductive age.
      INTERVENTION(S): Peritoneal fluid and sera were collected, and some women
      received gonadotropin-releasing hormone agonist (GnRH-a) therapy for
      endometriosis. MAIN OUTCOME MEASURE(S): Peritoneal fluid and sera TIMP-1
      concentrations were measured with a specific RIA. RESULT(S): The TIMP-1
      concentrations were significantly lower in PF and sera of women with
      endometriosis compared with disease-free women. The GnRH-a therapy restored serum
      TIMP-1 concentrations. CONCLUSION(S): Aberrant expression and localization of
      TIMP-1 may derange the proteolytic milieu of the peritoneal cavity and contribute
      to the etiology and underlying physiologic sequelae associated with
      endometriosis. Measurement of TIMP-1 in serum may aid in diagnosing endometriosis
      and assist with monitoring treatment efficacy in women with this disease.

PMID- 9627305
TI  - The follicular endocrine environment in stimulated cycles of women with
      endometriosis: steroid levels and embryo quality.
AB  - OBJECTIVE: To assess the endocrine milieu in follicles of stimulated cycles
      comparing women with and without endometriosis. Steroids were measured in
      follicular fluid (FF) and in in vitro culture of granulosa-luteal cells, and this
      status was related to the quality of the embryos obtained after IVF. DESIGN: Case
      control study. SETTING: IVF program at the Instituto Valenciano de Infertilidad.
      PATIENT(S): Twenty-four women with laparoscopically documented endometriosis and
      26 controls undergoing IVF. INTERVENTION(S): Individual follicular aspiration,
      oocyte isolation, FF storage, and preparation of luteinized granulosa cells for
      culture; oocyte insemination and embryo cleavage in standard IVF. MAIN OUTCOME
      MEASURE(S): Serum (day of ovum pickup) and FF measurements of estradiol,
      progesterone, testosterone, and androstenedione. Secretion of progesterone was
      measured in the cell-conditioned medium. Results were compared between patients
      with endometriosis and controls, as well as between oocytes that yielded embryos
      of different quality. RESULT(S): Levels of progesterone in the FF increased with
      the severity of the disease, whereas testosterone accumulation in the FF
      decreased with the severity of the disease. An increase in progesterone
      accumulation in vitro was observed in basal and hCG-induced granulosa cell
      cultures. No difference was observed in terms of embryo quality, and no steroid
      marker was able to identify follicles with oocytes that displayed embryos of good
      or bad quality under the inverted microscope. CONCLUSION(S): The data show
      differences in the steroidogenesis of follicles from stimulated women with and
      without endometriosis. These changes indicate good endocrine health but are not
      predictive of embryo quality.

PMID- 9627306
TI  - Acute changes in endometrial thickness after aspiration of functional ovarian
      cysts.
AB  - OBJECTIVE: To evaluate the influence of aspiration of functional ovarian cysts on
      endometrial thickness. DESIGN: Prospective study. SETTING: An IVF Unit of an
      academic medical center. PATIENT(S): Twenty-two patients from our IVF program, in
      whom administration of a gonadotropin-releasing hormone agonist preparation in
      the "long protocol" failed to induce pituitary desensitization, as evidenced by a
      serum E2 concentration of >55 pg/mL and the presence of an ovarian cyst of >20 mm
      in diameter. INTERVENTION(S): Transvaginal ultrasonographic-guided cyst
      aspiration was performed, and 2 days later, serum E2 concentration and
      endometrial thickness were reassessed. MAIN OUTCOME MEASURE(S): The values of
      serum E2 concentration and endometrial thickness before and after cyst aspiration
      were compared. RESULT(S): Two days after ovarian cyst aspiration, the serum E2
      concentration dropped from a mean (+/-SD) of 203 +/- 93 to 37 +/- 34 pg/mL. The
      mean (+/-SD) endometrial thickness was 9.6 +/- 2.0 mm before cyst aspiration and
      decreased to 5.9 +/- 2.4 mm after the procedure. CONCLUSION(S): Within 48 hours
      after ovarian cyst aspiration, a significant reduction in endometrial thickness
      occurs concomitant with a sharp decline in serum E2 levels. The phenomenon of
      acute reduction in endometrial thickness in response to acute estrogen withdrawal
      has not been described previously. The exact mechanism and endometrial component
      involved in the "shrinking" process should be further investigated.

PMID- 9627307
TI  - Basic fibroblast growth factor: peritoneal and follicular fluid levels and its
      effect on early embryonic development.
AB  - OBJECTIVE: To investigate the effect of basic fibroblast growth factor (FGF) on
      preimplantation embryos and to evaluate the levels of basic FGF in follicular and
      peritoneal fluid. DESIGN: Prospective study. SETTING: University-based
      laboratory. PATIENT(S): Follicular fluids (FFs) were obtained from women
      undergoing ovulation induction (n = 62) and peritoneal fluids were obtained from
      women with (n = 49) or without (n = 12) endometriosis. INTERVENTION(S): The
      effect of basic FGF on mouse embryos was assessed. Basic FGF concentrations were
      measured in pre-hCG and post-hCG FFs and in peritoneal fluids. MAIN OUTCOME
      MEASURE(S): Two-cell murine embryos were treated with basic FGF and followed for
      the rate of blastocyst formation and embryo hatching. Follicular and peritoneal
      fluid basic FGF levels were measured by ELISA. RESULT(S): Basic FGF (10 ng/mL)
      decreased the rate of blastocyst formation and embryo hatching. The level of
      basic FGF did not change in the FF around ovulation, and there was no correlation
      between FF basic FGF levels and reproductive parameters, with the exception of
      age. The levels of basic FGF in the peritoneal fluid of women with or without
      endometriosis were not different. CONCLUSION(S): Basic FGF is present in
      follicular and peritoneal fluids, but its concentration in these fluids does not
      change during the menstrual cycle or in the presence of endometriosis. Basic FGF
      inhibits murine preimplantation embryonic development at concentrations 10-100
      times higher than the levels detected in follicular and peritoneal fluids.

PMID- 9627308
TI  - Successful pregnancy with sperm retrieved from the bladder after the introduction
      of a low-electrolyte solution for retrograde ejaculation.
AB  - OBJECTIVE: To determine the safety and efficacy of the introduction of a low
      electrolyte solution into the bladder before masturbation for sperm recovery in
      patients with retrograde ejaculation. DESIGN: Two case reports. SETTING: Assisted
      reproduction practice at a university hospital. PATIENT(S): Two men with
      retrograde ejaculation. INTERVENTION(S): A 0.32-mol/L glucose solution or Ham's
      modified F-10 medium (GIBCO, Grand Island, NY) with 10% serum was introduced into
      the urinary bladder before masturbation. The retrieved sperm were used for IUI.
      MAIN OUTCOME MEASURE(S): The motility of retrieved sperm, achievement of
      pregnancy, and outcome of pregnancy. RESULT(S): In patient 1, the motility rate
      of sperm retrieved from the bladder after the introduction of Ham's modified F-10
      medium was higher than that after the introduction of a glucose solution. The
      patient's wife did not become pregnant during 10 IUI cycles after treatment with
      Ham's modified F-10 medium. However, she became pregnant during the first IUI
      cycle after treatment with a glucose solution and was delivered of healthy twin
      infants. The wife of patient 2 also became pregnant during the first IUI cycle
      after treatment with a glucose solution and was delivered of a healthy female
      infant. CONCLUSION(S): The introduction of a glucose solution appears to be a
      safe and simple method for sperm recovery in patients with retrograde
      ejaculation.

PMID- 9627309
TI  - The role of three-dimensional ultrasonographic images in ovarian measurement.
AB  - OBJECTIVE: To determine whether three-dimensional ultrasonography can increase
      the ability to evaluate the ovary and follicles, especially in women with
      polycystic ovary disease (PCOD). DESIGN: Prospective clinical study. SETTING:
      University hospital endocrine and infertility center. PATIENT(S): Sixty-six
      patients undergoing routine gynecologic evaluation were divided into two groups:
      the normal control group consisted of 22 patients, and there were 44 patients
      with PCOD. INTERVENTION(S): Three-dimensional ultrasonography was performed to
      store and document whole volumes of the ovaries for evaluation. MAIN OUTCOME
      MEASURE(S): Three perpendicular planes of bilateral ovaries are rotatable to
      obtain the largest dimensions. The three-dimensional volume was measured using
      the trapezoid formula. RESULT(S): The ovaries of the patients with PCOD were
      larger in size, area, and volume than those of normal controls. CONCLUSION(S):
      Stroma and volume determinations can be obtained more accurately by three
      dimensional images than by traditional ultrasonography. Three-dimensional
      ultrasonography not only facilitates noninvasive evaluation and volume
      calculation but also completes the examination in a short time without increasing
      patient discomfort.

PMID- 9627310
TI  - Numbers of embryos transferred or other factors?

PMID- 9627311
TI  - Clomid in unexplained infertility.

PMID- 9627312
TI  - Selection biases in semen study?

PMID- 9627313
TI  - Selection biases in semen study?

PMID- 9627314
TI  - Selection biases in semen study?

PMID- 9627315
TI  - Is IVF/ICSI always the first step to treat couples with infertility due to
      retrograde ejaculation?

PMID- 9627316
TI  - Technetium-99m-DTPA images of a renal cell carcinoma arising in a crossed-ectopic
      fused kidney.

PMID- 9627317
TI  - MURR--the world's most powerful university research reactor. University of
      Missouri Research Reactor.

PMID- 9627318
TI  - Explorer of the mysteries of the atom.

PMID- 9627319
TI  - Radiopharmaceutical Measurement Assurance Program provides significant cost
      savings.

PMID- 9627320
TI  - ACNP/SNM Government Relations Office midyear report: January-May 1998. American
      College of Nuclear Physicians/Society of Nuclear Medicine.

PMID- 9627321
TI  - Improved myocardial fatty acid metabolism after coronary angioplasty in chronic
      coronary artery disease.
AB  - This study assessed the utility of myocardial fatty acid imaging using 123I
      labeled 15-(beta-methyl-p-iodophenyl-pentadecanic acid (BMIPP) to evaluate
      improvement after percutaneous transluminal coronary angioplasty in patients with
      chronic coronary artery disease. METHODS: Thirty-eight patients (18 old
      myocardial infarction and 20 angina pectoris patients) with chronic coronary
      artery stenosis and 8 control subjects were enrolled in this study. All patients
      underwent successful angioplasty, and BMIPP SPECT was performed before and after
      angioplasty. SPECT images were divided into 13 segments and scored visually from
      0 (normal uptake) to 4 (defect). The defect score was calculated as the summation
      of the total scores in each patient. The regional washout rate was calculated in
      both the reperfused areas and normal uptake areas using a bull's-eye map.
      RESULTS: In nonrestenosis patients, BMIPP defect scores before and after
      angioplasty did not change on the initial image (9.6 +/- 9.3 compared to 9.0 +/-
      9.2, nonsignificant p value), whereas they improved significantly on the delayed
      image (9.9 +/- 8.8 compared to 8.2 +/- 8.7, p < 0.05). In nonrestenosis patients,
      BMIPP washout rate in reperfused areas after angioplasty was significantly lower
      than that before angioplasty and the washout rate in control subjects (22.9% +/-
      8.4% compared to 31.5% +/- 10.6% and 29.5% +/- 8.0%, p < 0.01 and p < 0.05,
      respectively). In restenosis patients, BMIPP washout rate in both reperfused
      areas and normal uptake areas did not change after angioplasty. CONCLUSION: These
      data suggest that decreased BMIPP washout rate after angioplasty indicates
      improved fatty acid utilization in patients with chronic coronary artery disease.

PMID- 9627322
TI  - First-pass radionuclide angiography using iodine-123 myocardial tracers and a
      multicrystal gamma camera.
AB  - The purpose of this study was to validate the accuracy of the assessment of
      ventricular function by first-pass radionuclide angiography (FPRNA) with 123I
      myocardial tracers and a multicrystal gamma camera. METHODS: Left ventricular
      ejection fraction (LVEF) and right ventricular ejection fraction were measured in
      69 patients by FPRNA using 123I myocardial tracers (126 +/- 7 MBq) and 99mTc
      tracers (541 +/- 141 MBq) on a multicrystal gamma camera with a high-sensitivity
      collimator. For 44 patients, ejection fraction values measured by 123I-FPRNA were
      compared to those estimated by equilibrium radionuclide angiography (ERNA).
      Visual wall-motion analysis was also performed to judge clinical acceptability of
      123I-FPRNA images for identification of wall-motion abnormality. RESULTS: Mean
      LVEFs (%) estimated by 123I-FPRNA and by 99mTc-FPRNA were 49.6 +/- 13.6 and 49.1
      +/- 14.1, respectively (nonsignificant p value). An excellent correlation was
      found between LVEFs estimated by 123I-FPRNA and 99mTc-FPRNA (r = 0.96, s.e.e. =
      1.9%). Values of LVEF measured by 123I-FPRNA also demonstrated excellent
      correlation with those measured by ERNA (r = 0.95, s.e.e. = 2.2%). A good
      correlation was also noted between right ventricular ejection fractions measured
      by 123I-FPRNA and 99mTc-FPRNA (r = 0.72, s.e.e. = 4.0%). The Spearman rank
      correlation coefficient between 123I-FPRNA and ERNA wall-motion scores was 0.87
      (n = 135, p < 0.001). CONCLUSION: Resting ventricular function can be reliably
      measured with 123I-FPRNA in combination with a multicrystal gamma camera. This
      indicates that the assessment of ventricular function is feasible in conjunction
      with 123I myocardial imaging without an increase in cost or radiation dose to
      patients.

PMID- 9627323
TI  - Adenosine receptor blockade enhances myocardial stunning without a sustained
      effect on fluorine-18-FDG uptake postreperfusion.
AB  - The aim of this study was to determine whether adenosine receptor blockade before
      ischemia would enhance the degree of stunning and induce a sustained decrease in
      glucose uptake after reperfusion. METHODS: Stunning was induced in 14
      anesthetized swine by partially occluding the left anterior descending artery
      (LAD) for 20 min (> 80% flow reduction). Seven animals were pretreated with the
      nonspecific adenosine receptor blocker 8-phenyltheophylline (8-PT; 5 mg/kg),
      which decreased reactive hyperemia by an average of 38%. Myocardial glucose
      uptake was assessed 1 hr following reperfusion with PET and the glucose analog
      18F-fluorodeoxyglucose (FDG). RESULTS: Before ischemia, systolic shortening in
      the LAD region was 15% +/- 6% in the control group and 16% +/- 4% in the 8-PT
      group and in both groups was reduced to - 1% +/- 2% during ischemia. After
      reperfusion, systolic shortening was 7% +/- 3% in the control group and 2% +/- 3%
      in the 8-PT group (p < 0.05). Myocardial oxygen consumption before ischemia was
      4.58 +/- 3.03 micromol/min/g in the control group and 4.44 +/- 1.83
      micromol/min/g in the 8-PT group (ns) and neither were different after
      reperfusion. In the postischemic LAD region, myocardial glucose uptake was 0.18
      +/- 0.15 micromol/min/g in the control group and was similar to that of the 8-PT
      group (0.17 +/- 0.08 micromol/min/g; ns). CONCLUSION: The nonspecific adenosine
      blocker 8-PT enhanced the degree of stunning when given before ischemia but did
      not induce a sustained effect on myocardial glucose uptake after reperfusion.

PMID- 9627324
TI  - Technetium-99m-HMPAO brain SPECT in Behcet's disease.
AB  - Behcet's disease (BD) is an idiopathic multisystem disorder. Involvement of the
      central nervous system (CNS) occurs in 4%-48% of cases. The aim of this study was
      to evaluate 99mTc-hexamethyl propyleneamine oxime (HMPAO) SPECT findings in BD
      patients and eventually to detect CNS involvement by depicting cerebral blood
      flow disturbances. METHODS: Technetium-99m-HMPAO brain SPECT was performed on 33
      consecutive BD patients. Qualitative and quantitative evaluation of the cortical
      uptake was done using an automatic program that generated 32 regions of interest
      (ROIs). An uptake index for each ROI was obtained. Reference values were obtained
      from a healthy control group (n = 20). Twenty-five patients also had an MRI
      study. RESULTS: Twelve of 32 patients (36%) presented with a clinical
      neurological disorder. SPECT and visual evaluation revealed that 17 patients
      (51.5%) had abnormalities; 9 of 25 MRI studies (36%) were abnormal. Using the
      quantitative approach for SPECT, 23 patients (69.7%) had abnormally low values.
      Six of 12 patients with neurological symptoms had a visually abnormal SPECT scan,
      whereas quantitative analysis showed abnormalities in 11 patients. Of the 21
      patients with no neurological findings, 9 had abnormal SPECT results, and 12 had
      low uptake indexes. CONCLUSION: HMPAO brain SPECT shows high rates of cerebral
      blood flow abnormalities in BD patients presenting with neuropsychiatric
      symptoms, and it also is frequently abnormal in asymptomatic BD patients who have
      no abnormalities on MR scans. Compared with visual analysis, quantitative
      analysis detects an even higher rate of SPECT changes in BD patients.

PMID- 9627325
TI  - Loss of dopamine-D2 receptor binding sites in Parkinsonian plus syndromes.
AB  - This study analyzed temporal changes of striatal dopamine-D2 receptor binding
      during the course of different extrapyramidal movement disorders using 123I
      iodobenzamide (IBZM) SPECT. METHODS: Eighteen patients (9 with Parkinson's
      disease, 9 with parkinsonian plus syndrome) were followed for 11-53 mo. Dopamine
      D2 receptor binding was assessed using 123I-IBZM SPECT at the beginning and at
      the end of the follow-up period. SPECT data were acquired 120 min postinjection
      of 3-5 mCi 123I-IBZM. A semiautomated algorithm was applied to the raw data for
      semiquantitative evaluation of regional cerebral receptor binding. RESULTS:
      Intraobserver (r = 0.992) and interobserver (r = 0.930) variance was low for the
      semiautomated interpretation of the SPECT examination of the dopaminergic D2
      receptor binding, reflecting a highly reproducible SPECT algorithm. Mean specific
      dopamine-D2 receptor binding was lower in patients with parkinsonian plus
      syndrome compared to patients with Parkinson's disease on the initial (p < 0.001)
      as well as the follow-up study (p < 0.001). In patients with Parkinson's disease,
      we observed an unaffected receptor binding compared to a reduced binding of
      radiotracer in patients with parkinsonian plus syndrome during the course of the
      disease (p < 0.001). CONCLUSION: During the follow-up, patients with Parkinson's
      disease showed a constant dopamine-D2 receptor binding. In contrast, patients
      with parkinsonian plus syndrome revealed a decline of the binding of dopamine-D2
      receptor. These findings are in agreement with histopathological data that
      demonstrated a preserved dopamine-D2 receptor status in patients with Parkinson's
      disease and a decline of the dopamine-D2 receptors in patients with parkinsonian
      plus syndrome. SPECT examinations using 123I-IBZM are useful for assessing
      dynamic changes of dopamine-D2 receptors in extrapyramidal movement disorders.
      Semiquantitative SPECT evaluations may provide valuable information for clinical
      management and prognosis of the patient with extrapyramidal movement disorders.

PMID- 9627326
TI  - SPECT findings in mitochondrial encephalomyopathy.
AB  - We investigated the alterations in regional cerebral blood flow (rCBF) in
      mitochondrial encephalomyopathy (MEM), using [123I]N-isopropyl-p-iodoamphetamine
      (IMP) or 99mTc-hexamethyl propyleneamine oxime SPECT in 10 MEM patients. METHODS:
      Four of the patients had MEM with lactic acidosis and strokelike episodes
      (MELAS), 2 had Kearns-Sayre syndrome (KSS), 1 had myoclonic epilepsy with ragged
      red fibers (MERRF) and 3 had cytochrome C oxidase deficiency (CCOD). Cerebral
      perfusion reserve was obtained from 6 patients (3 MELAS, 1 MERRF, 1 KSS, 1 CCOD)
      for a comparative analysis using the split-dose 123I-IMP SPECT method before and
      after the injection of acetazolamide. RESULTS: All patients with MELAS showed
      focal hypoperfusion in the parietal and/or occipital lobes. Follow-up studies (3
      MELAS patients) revealed extension or improvement in the abnormal perfusion. The
      hypoperfused lesions were correlated with abnormal CT/MRI findings. Perfusion was
      normal in 1 MERRF, 2 KSS and 3 CCOD patients, whereas CT/MRI findings in 1 MERRF,
      1 KSS and 1 CCOD patient were abnormal. The cerebral perfusion reserve in 3 MELAS
      patients was decreased significantly compared with that in patients with other
      types of MEM (MELAS 7.4%, other MEM 33.8%; p < 0.05). CONCLUSION: The rCBF was
      altered specifically in patients with MELAS, suggesting that brain perfusion
      SPECT will be useful in diagnosing and assessing such patients. The decreased
      cerebral perfusion reserve in patients with MELAS may represent an important
      feature of the pathogenesis of the strokelike episodes. The SPECT findings of
      patients with other types of MEM (MERRF, KSS and CCOD) were normal.

PMID- 9627327
TI  - Use of singular value decomposition to characterize age and gender differences in
      SPECT cerebral perfusion.
AB  - The main objective of this study was to characterize changes in brain perfusion
      associated with normal aging and gender. METHODS: Perfusion SPECT images using
      99mTc-hexamethyl propyleneamine oxime (HMPAO) were obtained from 152 healthy
      subjects (67 men, 85 women) aged 50-92 yr. An automated method was developed to
      objectively assess image data from a large number of brain regions. Image data
      were reduced with singular value decomposition (SVD), which produced 20
      eigenvectors capturing 97.05% of the total information content of 4320 regions
      from each subject. Subjects were scored individually on each vector. RESULTS:
      Multivariate analyses demonstrated that there were no significant differences in
      whole-brain HMPAO uptake with age, but age-related regional declines were seen in
      lateral ventricular regions. Women had higher HMPAO uptake than men in estimates
      of global perfusion and regional perfusion in the midcingulate/corpus callosum,
      inferior temporal and inferior parietal areas. CONCLUSION: These discriminations
      demonstrate that singular value deomposition of SPECT data may be used to assess
      differences in perfusion patterns between groups of subjects. They replicate
      several previous findings, both with respect to age-related changes in perfusion
      and with respect to gender differences. In addition, they identify a previously
      unreported gender difference in biparietal regions.

PMID- 9627328
TI  - Carbon-11-methionine PET in focal cortical dysplasia: a comparison with fluorine
      18-FDG PET and technetium-99m-ECD SPECT.
AB  - Focal cortical dysplasia is one of the known neuronal migration disorders and has
      recently been recognized as a cause of intractable epilepsy. In this study, we
      assessed the 11C-methionine (MET) uptake in focal cortical dysplasia by PET, and
      then compared the results with that of 18F-fluoro-2-deoxy-D-glucose (FDG) PET and
      99mTc-ethyl cysteinate dimer (ECD) SPECT. METHODS: Four patients (3 men, 1 woman;
      age range 16-68 yr) were examined by PET and SPECT for a presurgical examination
      of medically intractable seizures. In all 4 patients, 11C-MET PET was performed
      for 15 min, started 15 min after the administration of 511-662 MBq MET. In 3 of 4
      patients, FDG PET was performed for 15 min, and started 20 min after the
      administration of 185-370 MBq FDG. In all 4 patients, the cerebral blood flow was
      also evaluated by 99mTc-ECD SPECT for 15 min after the administration of 600 MBq
      ECD. RESULTS: In MET PET, all 4 lesions were visually recognized to have high MET
      uptake areas. The MET uptake of the lesions was 1.44 +/- 0.30 for the
      standardized uptake value (SUV) (ranging from 0.99-1.61). In FDG PET, 2 lesions
      were demonstrated to have low uptake areas (3.82 in SUV) while 1 had an ictal
      high uptake (4.74 in SUV). In ECD SPECT, 1 lesion demonstrated hypoperfusion and
      1 ictal hyperperfusion while 2 showed no abnormalities. All 4 patients underwent
      a cortical resection and the microscopic examinations were consistent with those
      of focal cortical dysplasia but no evidence of a tumor was found. CONCLUSION: MET
      PET is useful for identifying focal cortical dysplasia as a high uptake area.

PMID- 9627329
TI  - Preictal SPECT in temporal lobe epilepsy: regional cerebral blood flow is
      increased prior to electroencephalography-seizure onset.
AB  - Peri-ictal SPECT provides unique information on the dynamic changes in regional
      cerebral blood flow (rCBF) that occur during seizure evolution and, thus, could
      be useful in clarifying the poorly understood interplay of the interictal and
      ictal states in human focal epilepsy. The regional hyperperfusion observed on
      ictal SPECT is generally believed to be a consequence of electrical seizure
      activity. However, recent studies using invasive long-term cortical CBF
      monitoring have demonstrated that rCBF changes occur up to 20 min prior to ictal
      electroencephalography (EEG) onset. Because of apparent technical difficulties,
      no preictal SPECT studies have been reported so far. Therefore, we present our
      results on two patients with temporal lobe epilepsy in whom preictal SPECT scans
      were performed fortuitously under continuous video-EEG monitoring control.
      METHODS: Technetium-99m-hexamethyl propyleneamine oxime was injected 11 min
      (Patient 1) and 12 min (Patient 2) before clinical and EEG seizure onset, as
      documented from simultaneous video-EEG monitoring in two patients with temporal
      lobe epilepsy. We obtained accurate anatomical reference of CBF changes visible
      on SPECT by a special coregistration technique of MRI and SPECT. RESULTS: Whereas
      interictal SPECT showed a hypoperfusion of the temporal lobe ipsilateral to the
      seizure focus, on preictal SPECT, a significant increase in rCBF in the epileptic
      temporal lobe could be observed. These rCBF changes were not accompanied by any
      significant changes of the ongoing EEG. CONCLUSION: Our study provides evidence
      that rCBF is increased in the epileptic temporal lobe several minutes before EEG
      seizure onset. Thus, rCBF changes observed on peri-ictal SPECT scan cannot be
      considered a mere consequence of EEG seizure activity but may rather reflect a
      change in neuronal activity precipitating the transition from the interictal to
      the ictal state.

PMID- 9627330
TI  - In vitro and in vivo primate evaluation of carbon-11-etomidate and carbon-11
      metomidate as potential tracers for PET imaging of the adrenal cortex and its
      tumors.
AB  - METHODS: With the purpose of developing a PET imaging agent for tumors of the
      adrenal cortex, we developed syntheses for 11C-etomidate and its methyl analog,
      11C-metomidate. (R)-[O-ethyl-1-11C]Etomidate and (R)-[O-methyl-11C]metomidate
      were prepared by reaction of the appropriate respective 11C-labeled alkyl iodide
      and the tetrabutylammonium salt of the carboxylic acid derivative. The
      specificity of binding to the adrenal cortex was tested through the use of frozen
      section autoradiography of different tissues of the rat, pig and human.
      Inhibition of tracer binding was evaluated with etomidate, ketoconazole and
      metyrapone, well-known inhibitors of enzymes for steroid synthesis. Tracer
      binding to different human tumor samples was compared to immunohistochemical
      staining with antibodies for the steroid synthesis enzymes P450 11beta (11beta
      hydroxylase), P450 scc (cholesterol side-chain cleavage enzyme), P450 C21 (21 
      hydroxylase) and P450 17alpha (17alpha-hydroxylase). Three PET investigations,
      one with 11C-etomidate and two with 11C-metomidate, were performed in rhesus
      monkey sections, including the adrenals, liver and kidneys. Time-activity curves
      were generated from measured tracer uptake in these organs. RESULTS: In frozen
      section autoradiography of various tissues, high binding was seen in the adrenal
      cortex from all species, as well as in the tumors of adrenal cortical origin. The
      level of liver binding was about 50% of that in the adrenals, whereas that of all
      other organs was <10% of the adrenal binding. The adrenal binding was blocked by
      etomidate and ketoconazole at low doses but not by metyrapone. The binding in the
      adrenal tumor samples correlated with immunostaining for P450 11beta . PET
      studies in the monkey demonstrated high uptake in the adrenals with excellent
      visualization. The uptake increased with time without indication of washout.
      Slightly lower uptake was seen in the liver as compared to the adrenals, and in
      the late images, no organs other than adrenals and liver were seen. CONCLUSION:
      These investigations indicate that 11C-etomidate and 11C-metomidate have the
      potential to be useful specific agents for the visualization of the normal
      adrenal cortex and to provide positive identification of adrenal cortical tumors.

PMID- 9627331
TI  - PET imaging of prostate cancer using carbon-11-choline.
AB  - Prostate cancer is difficult to visualize using current techniques. Recently, 31P
      magnetic resonance spectroscopy has revealed that the tumor, in general, is
      characterized by an increased uptake of choline into the cell to meet increased
      synthesis of phosphatidylcholine, an important cell membrane phospholipid. We
      succeeded in using 11C-choline to visualize prostate cancer and its local
      metastasis in PET. METHODS: PET was performed on 10 prostate cancer patients from
      the level of pelvis to the lower abdomen. After transmission scanning, 370 MBq
      11C-choline were injected intravenously. The emission scan was performed 5-15 min
      postinjection. Finally, PET images were displayed so that each pixel was painted
      by a specified color representing the degree of the standardized uptake value
      (SUV). The 11C-choline image was compared with the 18F-fluorodeoxyglucose (FDG)
      image obtained from the same patient. RESULTS: Imaging of prostate cancer and its
      local metastasis was difficult when 18F-FDG was used because, within the pelvis,
      the areas of high uptake were concealed by the overwhelmingly abundant
      radioactivity in urine (in ureters and bladder). By contrast, it was easy when
      11C-choline was used because the urinary activity was negligible and tumor uptake
      was marked. The radioactivity concentration of 11C-choline in prostate cancer and
      metastatic sites was at an SUV of more than three in most cases. The SUV of 18F
      FDG was considerably lower than that of 11C-choline. CONCLUSION: Prostate cancer
      and its local metastasis were visualized clearly in PET using 11C-choline.

PMID- 9627332
TI  - Differential accumulation of iodine-123-iodobenzamide in melanotic and amelanotic
      melanoma metastases in vivo.
AB  - Iodine-123-iodobenzamide (IBZM) is a specific antagonist of dopamine D2 receptors
      and usually is used to study neuropsychiatric disorders. It also has a
      substantial affinity for malignant melanomas. This has been attributed to
      specific dopamine D2 receptor binding on melanoma cells because melanocytes and
      dopaminergic neurons share the same ectodermal origin and are both able to
      produce melanin. However, IBZM binding to melanoma metastases occurs
      predominantly 24 hr after injection, which is much later than maximal specific D2
      receptor binding is expected. Furthermore, IBZM binding is not consistent in
      melanoma patients. This points to another mechanism of IBZM binding to melanoma
      cells. The aim of this study was to characterize IBZM-binding metastatic melanoma
      patients clinically and histologically to shed light on the nature of this
      mechanism. METHODS: Twenty-one patients with proven or suspected metastases of a
      malignant melanoma entered this prospective study after surgical removal of the
      primary tumor. Whole-body scans, planar scintigrams and SPECT scans were
      performed 2-5 hr and 1 day after intravenous injection of 185 MBq IBZM. RESULTS:
      The suspected diagnosis of metastatic cancer was later confirmed in 17 patients
      by histology, clinical follow-up, x-ray, CT or other radiologic methods. Four
      patients were free of tumor tissue at the time of investigation and remained
      stable for 2 yr thereafter. Twelve of the 17 patients had a melanotic and 5 had
      an amelanotic subtype of the tumor. Iodine-123-IBZM accumulation occurred in the
      metastases of 10 of the 12 patients with melanotic melanoma and in 0 of the 5
      patients with the amelanotic tumor type (p < 0.01; chi-square test). Furthermore,
      IBZM accumulation occurred in 0 of the 11 amelanotic metastases but in 20 of the
      25 melanotic metastases (p < 0.001). The sensitivity is, thus, 83% for the
      detection of melanotic melanoma metastases on a patient basis and 80% on a lesion
      basis. Iodine-123-IBZM scintigraphy demonstrated one previously unknown
      metastasis. Six initially suspected lesions were not due to melanoma metastases
      and were IBZM-negative. No false-positive IBZM accumulations occurred in our
      patients. CONCLUSION: Iodine-123-IBZM binds to melanotic malignant melanomas with
      high specificity and moderate sensitivity but not to amelanotic melanomas. Our
      data suggest that the tracer does not bind to membrane dopamine receptors of the
      tumor but is built in or closely bound to intracellular melanin.

PMID- 9627333
TI  - Evaluation of esophageal cancers using fluorine-18-fluorodeoxyglucose PET.
AB  - To evaluate glucose metabolism in esophageal cancer, 48 patients were studied
      using PET with 18F-2-fluoro-2-deoxy-D-glucose (FDG). METHODS: After transmission
      scans were obtained, 18F-FDG (148 MBq) was administered intravenously. In 11
      patients, a dynamic study was performed to evaluate glucose metabolism. Using the
      changes of radioactivity in both plasma and tumor, rate constants (k1-k4) defined
      in the metabolic model for 18F-FDG were calculated. In 48 patients, static PET
      scans of the tumor (5-min scans) were obtained 60 min after administration.
      Fluorine-18-FDG activity within each tumor was corrected for physical decay and
      normalized by dose administration and patient weight to produce a standardized
      uptake value (SUV). RESULTS: Both the k3 value (n = 11) reflecting hexokinase
      activity and SUV (n = 13) were well correlated with hexokinase activity from the
      resected specimen (p < 0.05). Forty-seven of 48 patients before treatment
      revealed SUV greater than 2.0, but 10 normal control subjects and 1 esophageal
      benign tumor revealed less than 2.0 (accuracy rate 98.3%). Although
      clinicopathological findings did not correlate with SUV, except for two patients
      with carcinosarcoma, 23 patients with an SUV greater than 7.0 had a poor
      prognosis compared with 25 patients with SUVs less than 7.0. CONCLUSION: These
      findings suggest that 18F-FDG PET may be useful in distinguishing malignant
      tumors from benign lesions and in the preoperative evaluation of the prognostic
      factor.

PMID- 9627334
TI  - Iodine-131-MIBG scintigraphy in adults: interpretation revisited?
AB  - Iodine-131-metaiodobenzylguanidine (MIBG) scintigraphy is a reliable method used
      to diagnose pheochromocytoma. Although the adrenal medulla usually is not
      visualized, faint uptake can be observed in 16% of the patients 48-72 hr after
      injection of 18.5-37 MBq 131I-MIBG. We recently observed an increase in the
      frequency of visualization of the adrenal medulla in patients injected with 74
      MBq 131I-MIBG. Therefore, we retrospectively evaluated the pattern of uptake and
      potential changes between 1984 and 1994. METHODS: Scintigraphic data from 103
      patients referred for suspected pheochromocytoma were reviewed randomly. Data
      from 19 patients with medullary thyroid carcinoma were analyzed separately.
      Patients were injected with 74 MBq 131I-MIBG and imaged at 24 hr postinjection,
      48 hr postinjection, or both. Adrenal uptake was scored visually as 0 (no visible
      uptake) and 1 (uptake just visible) to 4 (most intense activity in the picture).
      Semiquantitative indicies were evaluated for discriminating between normal
      adrenal medullae and pheochromocytomas. Twenty-seven pheochromocytomas were
      surgically proven in 25 patients. RESULTS: A visual score > or =3 was noted in
      81% and 90% of the pheochromocytomas at 24 hr and 48 hr postinjection,
      respectively. From 1984 to 1988, 16% and 31% of adrenal medullae were seen at 24
      and 48 hr postinjection, respectively, whereas from 1989 to 1994, 56% and 73%
      were visualized at 24 and 48 hr postinjection, respectively. Before 1989, the
      best cutoff criterion to identify a pheochromocytoma, determined from receiver
      operating characteristic curve analysis, was a score > or =1 at 24 hr and > or =3
      at 48 hr postinjection, with a sensitivity and specificity of 92% and 84% at 24
      hr and 92% and 99% at 48 hr postinjection. From 1989, the best cutoff was a score
      > or =3 at both imaging sessions, with a sensitivity and specificity of 82% and
      100% at 24 hr and 100% and 97% at 48 hr postinjection. Among the semiquantitative
      indicies, the adrenal-to-liver and adrenal-to-heart ratios were the best
      discriminators between normal and pathological adrenals. They were, however, of
      little use because of the overlap between normal adrenal medullae and
      pheochromocytomas. CONCLUSION: The high rate of visualization of the normal
      adrenal medulla in this study was related to the larger-than-usual injected dose
      (74 MBq). Over recent years, however, this rate has been increasing, possibly
      because of the increased specific activity of 31I-MIBG. Adequate interpretation
      should take into account that a faint or definite uptake may be visible in more
      than 50% of normal adrenal medullae.

PMID- 9627335
TI  - Changes in radioiodine turnover in patients with autonomous thyroid adenoma
      treated with percutaneous ethanol injection.
AB  - In 24 patients with autonomous thyroid adenoma, we studied the hormonal pattern
      (free thyroxine, free triiodothyronine and thyroid stimulating hormone) and
      markers of radioiodine turnover before and after nodule ablation with
      percutaneous ethanol injection. METHODS: The hormonal pattern was studied before
      treatment and at various intervals after nodule ablation. Changes in radioiodine
      turnover were studied measuring 131I protein-bound iodine and the biologic half
      life of radioiodine in the thyroid (calculated from thyroid uptake at 24 and 48
      hr) before and after ethanol treatment. RESULTS: The hormonal pattern was
      normalized by treatment in all patients and remained normal for the follow-up
      period. Before treatment, protein-bound 131I was elevated in all patients but 4;
      after treatment, it normalized in 15 patients with the disappearance of the
      adenoma on scintigraphy. In the remaining 9 patients with only partial nodule
      destruction on scintigraphy, protein-bound 131I remained elevated although
      markedly reduced. Biologic half-life was shortened in 18 of 24 patients before
      treatment; after treatment, it was normal in 18 of 24 patients (13 of 15 with
      complete nodule ablation and 5 of 9 with partial ablation). CONCLUSION: Ethanol
      treatment normalized the hormonal pattern in all patients. Measures of
      radioiodine turnover were better markers of residual disease in that they
      normalized in almost all patients with complete nodule ablation, whereas they
      remained abnormal in a high proportion of patients with incomplete ablation.
      Thyroid hormones remained normal over a follow-up period of 3-7 yr in all
      patients.

PMID- 9627336
TI  - Fluorine-18-FDG PET imaging is negative in bronchioloalveolar lung carcinoma.
AB  - The goals of our study were to establish PET accuracy with 18F-fluorodeoxyglucose
      (FDG) in finding localized formations of bronchioloalveolar lung carcinoma (BAC)
      and to investigate the correlation between FDG uptake and the degree of cell
      differentiation in adenocarcinoma of the lung. MATERIALS: Twenty-nine patients
      with 30 adenocarcinomas of the lung (7 bronchioloalveolar lung carcinomas, 9 well
      differentiated, 2 well-moderately differentiated, 11 moderately differentiated
      and 1 poorly differentiated) were studied. All patients underwent thoracotomies
      within 4 wk after the FDG PET study. For qualitative analysis, the degree of FDG
      activity in the tumors was visually scored using a five-point grading system: 0 =
      same to background activity, 1 = less than mediastinal blood-pool activity, 2 =
      same to mediastinal blood-pool activity, 3 = slightly greater than mediastinal
      blood-pool activity and 4 = substantially greater than mediastinal blood-pool
      activity. Foci of activity with Grades 2-4 were considered tumors. For
      semiquantitative analysis, standardized uptake values (SUV) were calculated.
      RESULTS: In 7 BACs, 4 lesions (57%) showed negative results on FDG PET, while in
      23 non-BACs, only 1 lesion (4%), which was a well-differentiated adenocarcinoma
      showed a negative result. BACs' mean visual score (1.43 +/- 1.27) was
      significantly lower than that of non-BACs (3.17 +/- 1.03) (p = 0.001). The BACs'
      mean SUV (1.36 +/- 0.821) was significantly lower than that of well
      differentiated adenocarcinomas (2.92 +/- 1.28) (p = 0.014); the mean SUV of well
      differentiated adenocarcinomas was significantly lower than that of moderately
      differentiated adenocarcinomas (4.63 +/- 1.86) (p = 0.031). No significant
      differences were apparent in average size among these three histologic types.
      CONCLUSION: A correlation was observed between FDG uptake and the degree of cell
      differentiation in adenocarcinoma of the lung. FDG PET may show negative results
      for BAC.

PMID- 9627337
TI  - Influence of the heterogeneity of P-glycoprotein expression on technetium-99m
      MIBI uptake in breast cancer.
AB  - We prospectively studied a total of 30 patients with breast cancer to evaluate
      the relationship between the degree of accumulation of 99mTc-sestamibi (MIBI) and
      the heterogeneity of p-glycoprotein expression in tumor tissues. METHODS: Twenty
      patients during initial presentation and 10 patients during post-therapy
      evaluation underwent contemporaneous 99mTc-MIBI imaging and surgery or biopsy.
      Immunohistochemical studies were performed on multiple nonconsecutive sections of
      the same tumor using a p-glycoprotein-specific monoclonal antibody, JSB-1. Tumor
      to-background (T/B) ratios were correlated with the level and heterogeneity of p
      glycoprotein expression determined by immunohistochemical studies. RESULTS: The
      T/B ratios were lower for those tumors with strong p-glycoprotein expression
      (Group 1) than those with strong-to-weak expression (Group 2) or those with weak
      to-no expression (Group 3) (1.32 +/- 0.19 and 1.85 +/- 0.56 and 2.86 +/- 1.06,
      respectively). There was statistically significant difference in T/B ratios
      between all 3 groups (p < 0.005). Although T/B ratios for Group 1 and Group 3
      were clearly distinct from one another with no overlapping values, the values for
      Group 2 overlapped with those of Group 1 and Group 3. When we evaluated the
      entire patient group with excluding those with strong-to-weak expression,
      although the p value remained the same (p < 0.001), we obtained a stronger
      correlation between T/B ratios and p-glycoprotein expression (r = 0.808 versus
      0.735). CONCLUSION: Due to the heterogeneous expression of p-glycoprotein, both
      immunohistochemistry and 99mTc-MIBI scintigraphy may yield confounding results by
      contrasting with one another if the presence or absence of p-glycoprotein is not
      extensively explored. Although our data confirmed that 99mTc-MIBI imaging is
      useful in the determination of the presence of multidrug resistance in patients
      with breast cancer, the issue of heterogeneous expression of the antigen should
      be further investigated when unexpected results are obtained.

PMID- 9627338
TI  - L-[1-carbon-11]tyrosine imaging of metastatic testicular nonseminoma germ-cell
      tumors.
AB  - The aim of this study was to investigate whether PET with L-[1-11C]tyrosine
      C(TYR) can be used to visualize metastatic disease of nonseminoma testicular germ
      cell tumors and to monitor the effect of systemic cisplatinum-based
      polychemotherapy in a noninvasive fashion to reduce the number of operations in
      patients with a residual retroperitoneal tumor mass. METHODS: Ten patients with
      retroperitoneal nonseminoma testicular germ-cell tumors metastases were studied
      with TYR PET before the start of cisplatinum-based polychemotherapy. A dose of
      370 MBq of TYR was injected intravenously, and a 30-min TYR image was acquired 20
      min after injection. The standardized uptake value of TYR was calculated in
      visualized lesions. RESULTS: PET showed increased focal uptake of TYR in the
      retroperitoneum of 2 patients (20%). In 2 patients with large and inhomogeneous
      lesions on CT, PET showed decreased TYR uptake at the site of the lesion (20%).
      In the other 6 patients, the metastatic tumor masses were not depicted (60%).
      Because of these disappointing results, no posttreatment scans were obtained.
      Standardized uptake values of the visualized lesions varied from 1.05 to 2.87 for
      the lesions with increased metabolism and from 0.29 to 0.34 for lesions with
      decreased metabolism. CONCLUSION: PET with TYR is not suited to visualize the
      apparently slowly proliferating nonseminoma testicular germ-cell tumors or
      determine the nature of a residual retroperitoneal mass after chemotherapy.

PMID- 9627339
TI  - FDG PET: elevated plasma glucose reduces both uptake and detection rate of
      pancreatic malignancies.
AB  - The aim of the study was to evaluate the effects of elevated plasma glucose
      levels on tumor detection. METHODS: One-hundred and seventy-one fasted patients
      (100 malignant pancreatic tumors, 46 chronic pancreatitis and 25 patients with
      other benign pancreatic lesions) were studied with 18F-fluorodeoxyglucose (FDG)
      PET before planned resective pancreatic surgery. Nineteen of 171 patients had
      elevated plasma glucose levels above 130 mg/dl, and 24 of 171 had diabetes
      mellitus. Standard uptake values (SUVs) with and without glucose correction,
      tumor-to-muscle ratios and tumor-to-liver ratios were measured of the pancreatic
      lesion respective of the area with the highest uptake within the pancreas. The
      original qualitative PET reports concerning the dignity of the pancreatic lesion
      were translated into a five-point malignancy scale. Tumor detection rates and
      SUVs were compared according to plasma glucose levels above and below 130 mg/dl,
      the presence of diabetes and by using receiver operating characteristic (ROC)
      analysis. RESULTS: The detection rates (and mean SUVs) for pancreatic
      malignancies were 86% and 42% (4.2 and 2.3) if fasted plasma glucose levels were
      below and above 130 mg/dl, respectively. The sensitivities (and mean SUVs of
      malignant tumors) were 83% and 69% (3.3 and 2.5) for patients without and with
      known diabetes. Areas under ROC curves were nearly equal for glucose corrected
      SUV and visual qualitative results (0.86 and 0.85), followed by uncorrected SUV
      (0.83), tumor-to-liver ratios (0.80) and tumor-to-muscle ratios (0.79). SUVs for
      chronic pancreatitis, muscle and liver had a tendency to increase with elevated
      plasma glucose levels. CONCLUSION: Negative PET results of patients with elevated
      plasma glucose should be interpreted with caution.

PMID- 9627340
TI  - Bone marrow scintigraphy with technetium-99m anti-NCA-95 to monitor therapy in
      malignant osteopetrosis.
AB  - We report a case of a 2-mo-old girl with malignant osteopetrosis. Conventional
      radiological investigations of the skull and left hand showed the characteristic
      pattern of generalized sclerosis. Bone marrow immunoscintigraphy with 99mTc
      labeled antibodies against nonspecific cross-reactive antigen (NCA) 95 was
      performed before and after bone marrow transplantation. Before transplantation,
      whole-body images showed bone marrow stores exclusively in the base of the skull.
      The rest of the skeleton did not reveal any hematopoietic activity. The liver and
      spleen showed increased antibody uptake as expected in extramedullary
      hematopoiesis. Repeat scintigraphy after bone marrow transplantation from her
      haploidentical father demonstrated an almost completely normalized tracer
      distribution corresponding to her clinical and hematological improvement. Bone
      marrow immunoscintigraphy appears to be an ideal complement to radiograph
      diagnostics in malignant osteopetrosis. In primary diagnosis, scintigraphy
      demonstrates the quantitative extent of bone marrow displacement. It also proves
      an ideal tool in monitoring the effectiveness of therapy after bone marrow
      transplantation.

PMID- 9627341
TI  - Factors influencing the sensitivity of tumor imaging with a receptor-binding
      radiopharmaceutical.
AB  - The overexpression of cell surface receptors on cancer cells is a potential
      target for the design of receptor-binding radiopharmaceuticals for tumor imaging.
      The sensitivity of these agents depends on the interaction in vivo of factors
      such as the level and heterogeneity of receptor expression, the proportion of
      targeted cells, the tumor/ nontarget (T/NT) ratio and attenuation by overlying
      normal tissue. The relative importance of a single factor or combination of
      factors is unknown. Our objective was to evaluate, under controlled experimental
      conditions, the effect of these factors on the sensitivity for imaging breast
      cancer with a new receptor-binding radiopharmaceutical: human epidermal growth
      factor (HEGF)51 labeled with 111In. METHODS: MDA-MB-468, S1 or MCF-7 breast
      cancer cells expressing 1.3 x 10(6), 3.3 x 10(4) and 1.5 x 10(4) epidermal growth
      factor receptors (EGFR)/cell were targeted in vitro with 111In-HEGF51. Phantoms
      were constructed with an internal well to simulate a lesion and surrounded by an
      outer well to simulate normal tissue. The effect of the level of receptor
      expression was studied with phantoms containing targeted MDA-MB-468, S1 or MCF-7
      cells. The effect of the proportion of cells targeted was evaluated using
      phantoms containing mixed targeted or nontargeted MDA-MB-468 cells. Receptor
      heterogeneity was studied using phantoms containing mixed MDA-MB-468 and S1
      cells. The T/NT ratio was evaluated by varying the concentration of radioactivity
      in the outer well and tissue attenuation was simulated by overlaying the phantoms
      with water. Phantoms were imaged using a gamma camera fitted with a medium-energy
      collimator interfaced to a computer. RESULTS: The sensitivity for detection of a
      lesion was directly proportional to the level of receptor expression or to the
      proportion of cells targeted and inversely proportional to the level of receptor
      heterogeneity. A T/NT ratio > or = 2:1 was required for detection. Under ideal
      conditions with a single factor varied, as few as 5 x 10(4) to 10(5) MDA-MB-468
      cells with a high level of EGFR expression or 2.5 x 10(5) to 10(6) S1 or MCF-7
      cells with a low level of EGFR expression were detected. When the receptor
      heterogeneity, the proportion of targeted cells and tissue attenuation were
      varied in combination with a T/NT ratio of 3:1, the sensitivity for detection
      approached that observed clinically with receptor-binding radiopharmaceuticals
      (10(7) cells). CONCLUSION: Our results suggest that combinations of four factors
      may account for the relatively low sensitivity for tumor imaging observed
      clinically with receptor-binding radiopharmaceuticals and, in particular,
      strategies aimed at minimizing the effects of receptor heterogeneity; a low
      proportion of cells targeted and tissue attenuation would improve the detection
      of small lesions.

PMID- 9627342
TI  - Kinetic analysis of 2-[carbon-11]thymidine PET imaging studies: compartmental
      model and mathematical analysis.
AB  - Carbon-11-thymidine is a PET tracer of DNA synthesis and cellular proliferation.
      Quantitative analysis of [11C]thymidine images is complicated by the presence of
      significant quantities of labeled metabolites. Estimation of the rate of
      thymidine incorporation into DNA using [11C]thymidine requires a kinetic model
      that is capable of describing the behavior of thymidine and labeled metabolites.
      METHODS: Based on previous studies with labeled thymidine, we constructed a five
      compartment model describing the kinetic behavior of 2-[11C]thymidine and its
      labeled metabolites. In addition, we have performed a series of calculations and
      simulations to calculate the sensitivity and identifiability of model parameters
      to estimate the extent to which individual parameters can be estimated; to
      determine appropriate model constraints necessary for reproducible estimates of
      the constant describing flux of thymidine from the blood into DNA, i.e.,
      thymidine flux constant; and to determine the potential accuracy of model
      parameter and thymidine flux constant estimates from PET imaging data. RESULTS:
      The underlying assumptions in the thymidine compartmental model lead to a
      description of the thymidine flux constant for DNA incorporation in terms of
      model parameters. Sensitivity and identifiability analyses suggest that the model
      parameters pertaining to labeled metabolites will be difficult to estimate
      independently of the thymidine parameters. Exact evaluation of the kinetic
      parameters of the labeled metabolites is not the principal goal of this model.
      Simulations were performed that suggest that it is preferable to tightly
      constrain these parameters to preset values near the center of their expected
      ranges. Although it is difficult to estimate individual thymidine model
      parameters, the flux constant for incorporation into DNA can be accurately
      estimated (r > 0.9 for estimated versus true simulated flux constant). Flux
      constant estimates are not affected by modest levels of local degradation of
      thymidine that may occur in proliferating tissue. CONCLUSION: By using a kinetic
      model for thymidine and labeled metabolites, it is possible to estimate the flux
      of thymidine uptake and incorporation into DNA and, thereby, noninvasively
      estimate regional cellular proliferation using [11C]thymidine and PET.

PMID- 9627343
TI  - Assessing the limping child with skeletal scintigraphy.
AB  - Skeletal scintigraphy is frequently used in the clinical investigation of young
      children who present with limping as their only or predominant symptom. This
      article reviews techniques used for pediatric skeletal scintigraphy, skeletal
      tracer distribution in the immature skeleton and scintigraphic manifestations of
      relatively common conditions that can produce limping in children 1-6 yr old.
      Acute osteomyelitis, vertebral infections, transient synovitis, septic arthritis,
      Legg-Calve-Perthes disease, lower extremity injuries in toddlers and osteoid
      osteoma are emphasized.

PMID- 9627344
TI  - Differentiation of prolonged colonic transit using scintigraphy with indium-111
      labeled polystyrene pellets.
AB  - Prolonged colonic transit can be caused either by slow transit constipation or by
      pelvic outlet obstruction needing different therapeutic regimes. The aim of this
      study was to prove the value of scintigraphic assessment. METHODS: Colon
      scintigraphy was performed in 32 patients (28 women, 4 men; age range 8-68 yr)
      with idiopathic constipation at 8, 24 and 48 hr in ventral and dorsal projection
      after oral administration of a pH-sensitive, methacrylate-coated capsule of
      nonresorbable 111In-labeled polystyrene (cathion exchanger) micropellets (3.5
      MBq/capsule). The geometric center (GC) as the sum of products of colon segment
      activity and colon segment number (1 = colon ascendens; 2 = transverse colon; 3 =
      colon descendens; 4 = rectosigmoid colon; and 5 = stool) dividing by the total
      counts was used to determine the velocity of colonic transit at least at 24 hr as
      the proximal colonic emptying (PCE) rates. Stool activity was evaluated
      indirectly as decay-corrected colon activity loss between two examinations.
      Results were compared with data obtained from 22 healthy subjects. RESULTS:
      Twenty-six patients had a significant prolongation of colonic transit after 24
      and 48 hr (the 95% confidence interval of the patient's GC showed no overlap to
      the 95% confidence interval of GC calculated from 22 healthy controls as normal
      range) revealing slow transit constipation. Six patients had normal or
      accelerated transit (GCs and PCE rates) up to the rectum but delayed rectal
      emptying indicating pelvic outlet obstruction. CONCLUSION: By the help of this
      method it was possible to differentiate the two subtypes of colon transit
      prolongation by use of the reported scintigraphic technique, which leads to
      different therapeutic management of the patients. Compared with x-ray methods
      (Hinton test), this method has the capability of a continuous observation of
      colonic transit without increasing radiation exposure.

PMID- 9627345
TI  - Reproducibility of technetium-99m-MAG3 clearance using the Bubeck method.
AB  - The objective of this study was to estimate the reproducibility of 99mTc
      mercaptoacetyltriglycine (99mTc-MAG3) clearance calculated using a single-sample
      method. METHODS: One hundred forty-seven patients with urological or ear, nose
      and throat cancer were analyzed in a retrospective study. Each patient had at
      least two clearance studies with 99mTc-MAG3 before chemotherapy treatments to
      monitor renal function. Up to five clearance studies per patient were considered.
      The reproducibility was estimated by comparing two consecutive investigations.
      Pairs of investigations with a change in split renal function of more than 5% or
      an interval of more than 50 days were excluded. Clearance was determined using
      the Bubeck method. For each pair of consecutive clearance data, the difference
      between the first and the second measurements was expressed as a percentage of
      the mean value of the two measurements. The mean of these normalized differences
      represents the systematic deviation, and the s.d. represents the reproducibility
      of the compared clearances. RESULTS: After the selection, 242 pairs of
      consecutive clearance data remained for comparison. Significantly different
      clearances were observed only between investigations 0 and 1 and between 4 and 5.
      The systematic deviation of these comparisons totaled -3.8% and -5.7%,
      respectively. In the other comparisons, no significant deviation induced by the
      chemotherapy was found. The reproducibility calculated for all comparisons
      totaled 11.7%. CONCLUSION: The error of reproducibility of 99mTc-MAG3 clearance
      using the Bubeck method was < or =11.7%. This was an acceptable value, taking
      into account the greater fluctuation of tubular function compared with the
      glomerular filtration rate.

PMID- 9627346
TI  - Comparison of radionuclide scrotal blood-pool index versus gonadal venography in
      the diagnosis of varicocele.
AB  - The purpose of our study was to assess the value of a radionuclide scrotal blood
      pool index (SBPI) in diagnosing and grading clinical and subclinical varicocele.
      METHODS: Scrotal scans were performed on 1360 infertile patients. Thirty fertile
      patients with a normal scrotum on palpation served as controls. The patients' red
      blood cells were labeled in vivo by administration of stannous ions of
      pyrophosphate followed by the intravenous administration of 99Tc-pertechnetate.
      The scans initially were inspected visually and, when bilateral varicocele was
      excluded, a computerized analysis of the ratio of the blood-pool activity in each
      hemiscrotum (SBPI) permitted accurate grading of the varicocele. A subgroup of
      224 patients was selected randomly and had gonadal venography. The results of
      physical examination, scrotal scan, gonadal venography and semen analysis were
      compared. RESULTS: Normal values of SBPI (0.9-1.1) were derived from the control
      group. There was a 93.5% correlation between palpation and SBPI grade in
      diagnosing palpable varicocele. When compared to gonadal venography, subclinical
      varicocele was demonstrated by scrotal scan in 54.8% of infertile male patients
      with abnormal semen analysis, normal female partners and no other cause of
      infertility. Of these patients, 32.6% had, unexpectedly, Grade 2 or 3 varicocele.
      Right and bilateral varicocele were demonstrated three times as often by scrotal
      scan than by palpation. SBPI was accurate in diagnosing recurrent varicocele but
      there was a low correlation (61.1%) between SBPI and gonadal venography grade.
      There was a high correlation between SBPI grade and sperm analysis grade.
      CONCLUSION: SBPI grading of varicocele was validated as an accurate, quantitative
      and noninvasive method of grading varicocele, equivalent to the grading system by
      palpation in a large group of infertile patients. The main contribution of SBPI
      was in detecting and grading subclinical varicocele in infertile patients with no
      other cause of infertility. SBPI also was accurate in diagnosing but not in
      grading recurrent varicocele.

PMID- 9627347
TI  - Automatic three-dimensional matching of CT-SPECT and CT-CT to localize lung
      damage after radiotherapy.
AB  - The aim of this study was to develop a fast and clinically robust automatic
      method to register SPECT and CT scans of the lungs. METHODS: CT and SPECT scans
      were acquired in the supine position from 20 patients with healthy lungs. After
      partial irradiation of the lungs by radiotherapy, the scans were repeated. Two
      matching methods were compared: a conventional method with external skin markers
      and a new method using chamfer matching of the lung contours. In the latter
      method, a unique value for the SPECT threshold, needed for segmentation of the
      SPECT lungs, was determined by iteratively applying the chamfer matching
      algorithm. RESULTS: The new technique for CT-SPECT matching could be implemented
      in a fully automatic manner and required less than 2 min. No large systematic
      shifts or rotations were present between the matches obtained with the marker
      method and the lung contour method for healthy or partially irradiated lungs. For
      healthy lungs, the number of ventilation SPECT counts outside the CT-defined lung
      was taken as a measure for a good match. This number of outside counts was
      slightly lower for the new method than for the conventional method, which
      indicates that the accuracy of the new method is at least comparable to the
      conventional method. For ventilation, a systematic difference between the results
      of the matching methods, a small translation in the anterior --> posterior
      direction, could be attributed to an inconsistency of the marker positions (2
      mm). For perfusion, a somewhat larger anterior --> posterior shift was found,
      which was attributed to the gravity force. CT-CT correlation on the lung contours
      using chamfer matching was tested with the same dataset. For accurate matching,
      the CT slices encompassing the diaphragm had to be deleted. CONCLUSION: The new
      method based on lung contour matching is a fast, automatic procedure and allows
      accurate clinical follow-up.

PMID- 9627348
TI  - Scintigraphic screening prior to visceral arteriography in acute lower
      gastrointestinal bleeding.
AB  - We evaluated the effect on the diagnostic yield of visceral arteriography in
      patients with acute gastrointestinal bleeding of a protocol requiring a positive
      99mTc-red blood cell scintiscan before the performance of arteriography
      (scintigraphic screening). METHODS: A retrospective review was conducted of 249
      scintiscans and 271 arteriograms obtained over 99 mo, with scintigraphic
      screening implemented during the final 18 mo. RESULTS: Before the implementation
      of scintigraphic screening, arteriograms detected bleeding at a rate of 22%.
      After its implementation, 53% of the arteriograms detected bleeding. This
      represented a statistically significant increase (0.53 versus 0.22, p = 0.015).
      CONCLUSION: Scintigraphic screening appears to increase by a factor of 2.4 the
      diagnostic yield of arteriography by screening out patients who are not actively
      bleeding at the time of the examination, thus sparing them the risks and costs of
      a nondiagnostic invasive study.

PMID- 9627349
TI  - Epiphyseal photopenia associated with metaphyseal osteomyelitis and subperiosteal
      abscess.
AB  - We present a case of metaphyseal osteomyelitis in a child where bone scintigraphy
      demonstrated photopenia of the distal femoral epiphysis in the absence of
      infection of the epiphysis or the joint space. A subsequent bone scan
      demonstrated evolution of the vascular compromise of the epiphysis due to the
      metaphyseal osteomyelitis complicated by subperiosteal abscess. We discuss the
      mechanisms and implications of photopenia in the setting of acute bone and joint
      infection.

PMID- 9627350
TI  - Scintigraphic findings of fibular donor sites.
AB  - Vascularized fibulas are used for reconstruction of bony defects after surgical
      removal of malignant skeletal tumors. Here, we describe scintigraphic findings at
      fibular donor sites in three patients who underwent limb salvage procedures for
      primary malignant bone tumors.

PMID- 9627351
TI  - Imaging experimental osteomyelitis using radiolabeled liposomes.
AB  - We evaluated radiolabeled liposomes (liposomes labeled both with 99mTc and 111In)
      for the early detection of osteomyelitis in an experimental model. METHODS:
      Liposomes, containing 5% polyethylene glycol-distearoyl phosphatidylethanolamine
      with encapsulated glutathione and deferoxamine, were prepared and labeled with
      99mTc and 111In by a previously described method. Acute osteomyelitis was induced
      in male New Zealand rabbits by intramedullary injection of sodium-morrhuate and
      Staphylococcus aureus in the tibial bone marrow. Serial imaging studies,
      consisting of radiolabeled liposome imaging (2-4 mCi 99mTc and 75-125 microCi
      111In), 99mTc-methylene diphosphonate (MDP) (3-5 mCi) and 67Ga-citrate (500
      microCi), were performed starting at the third day after injection. Each
      radionuclide study was separated by at least 2 days. The animals also underwent
      radiography of the lower extremities. The animals were then killed and the
      infected tibia was excised for histopathology. RESULTS: For interpreting relative
      efficacy of individual radiopharmaceuticals, only animals showing positive
      histopathological findings (n = 9) were considered. Radiographs (Days 12, 13)
      were conclusive for osteomyelitis in only 3 rabbits. Radiolabeled liposome
      imaging (Days 4-6) showed positivity in 8 cases and was equivocal in 1. Though
      the lesion could be delineated as early as 8 hr postinjection in the 99MTc
      window, the best target-to-nontarget ratio (T/NT) of 1.86 +/- 0.19 was obtained
      at 48 hr in the 111In window. Three-phase 99mTc-MDP scan (Day 7) was positive in
      only 5 rabbits with 3 hr T/NT of 1.6 +/- 0.23. Galium-67-citrate images (Days 9
      11) were positive in 8 cases and equivocal in 1, the mean 48 hr T/NT being 1.74
      +/- 0.24. These results show liposomes are better than 99mTc-MDP for imaging bone
      infection. Given the early localization and better quality of the images,
      radiolabeled liposomes also exhibited advantages over 67Ga-citrate for detection
      of acute osteomyelitis.

PMID- 9627352
TI  - Enhanced accuracy and reproducibility in reporting of lung scintigrams by a
      segmental reference chart.
AB  - The diagnostic probability of pulmonary embolic disease is based on the
      recognition of unmatched segmental perfusion defects. Although interobserver and
      intraobserver reproducibility have been studied, accuracy has been an elusive
      goal due to the lack of a gold standard. We investigated the accuracy and
      reproducibility of reporting in a virtual scintigraphic model of the lungs, with
      and without the use of a lung segmental reference chart. METHODS: A Monte Carlo
      package was used to model lung scintigraphy from a digital phantom of the human
      lungs. An ideal lung segmental reference chart was created from the phantom. Five
      experienced nuclear medicine physicians reported a set of all possible defects
      involving 100% of a segment, without and with the chart. A further set of defects
      involving 45%-55% of a segment in the lower lobes was investigated using the
      chart. RESULTS: There was a significant improvement in accuracy (from 48% to 72%)
      and intraobserver agreement (from 61% to 77%) with the chart. The accuracy of
      reporting defects in the upper and middle lobes was consistently better than that
      in the lower lobes. There was no significant difference between the accuracy of
      reporting large defects and that of reporting moderate defects in the lower
      lobes. CONCLUSION: The lung segmental reference chart significantly improves both
      the accuracy and reproducibility of reporting lung scintigrams; however, although
      reporting in the lung bases is improved, absolute accuracy is substantially less
      than that in the upper and middle lobes. This emphasizes the need for caution
      because the lung bases are the most common site of embolic disease.

PMID- 9627353
TI  - Parathyroid imaging using simultaneous double-window recording of technetium-99m
      sestamibi and iodine-123.
AB  - Technetium-99m-sestamibi represents an important advance in the scintigraphic
      location of parathyroid neoplasms. However, the optimal procedure for 99mTc
      sestamibi parathyroid scanning has not been defined. The first objective of this
      work was to optimize the technical aspects of subtraction scanning, using
      simultaneous double-window recording of 99mTc-sestamibi and 1231 instead of
      successive image recording. The second objective was to compare two protocols for
      detecting abnormal parathyroid glands: subtraction scanning and single-tracer
      double-phase scanning. METHODS: Thirty patients referred for first surgery of
      primary hyperparathyroidism had both subtraction scanning and double-phase
      scanning in the same imaging session. Images of 99mTc-sestamibi and 123I were
      recorded simultaneously in nonoverlapping windows and then subtracted. For double
      phase scanning, images of 99mTc-sestamibi, acquired 15 min and 120 min after
      tracer injection, were visually compared. Surgery disclosed a solitary adenoma in
      27 patients, bilateral adenomata in 2 patients and 3 hyperplastic glands in the
      last patient. No patient had persistent hypercalcemia. RESULTS: Preoperative
      99mTc-sestamibi/123I subtraction scanning located 25 of 27 solitary adenomas, the
      bilateral adenomata and 3 of 3 hyperplastic glands. The overall sensitivity for
      enlarged parathyroids was 94%, and the false-positive image rate was 3%. The
      99mTc-sestamibi single-tracer technique located 22 of 27 solitary adenomas, the
      bilateral adenomata and 1 of 3 hyperplastic glands. Overall sensitivity was 79%
      and the false-positive image rate was 10%. The gamma camera imaging time was 30
      min for the subtraction technique and 50 min for the single-tracer double-phase
      study. An ectopic adenoma in the sheath of the right carotid artery was detected
      by both techniques. CONCLUSION: These results, together with other data in the
      literature, indicate that 99mTc-sestamibi/123I subtraction imaging is accurate in
      locating enlarged parathyroids. Classical difficulties of this technique (motion
      artifacts and prolonged immobilization) were avoided by using simultaneous
      recording of the two isotopes. In this series subtraction imaging was more rapid
      and more sensitive (p < 0.04) than the single-tracer technique.

PMID- 9627354
TI  - Transmission imaging for nonuniform attenuation correction using a three-headed
      SPECT camera.
AB  - Our objective was to build and test a new system for transmission CT (TCT)
      imaging on a three-headed SPECT camera. The TCT images are intended for use in
      nonuniform attenuation correction of cardiac SPECT data. METHODS: The system
      consists of a transmission line source mounted to the camera gantry at the focal
      line of a long focal length, asymmetric fanbeam collimator. The focal line is 114
      cm from the collimator surface and shifted 20 cm from the detector midline. This
      asymmetric fanbeam geometry is used to reduce truncation artifacts in the
      reconstructed TCT image. The line source fixture accommodates a 25-cm long source
      and contains removable, variable thickness attenuator plates (copper or lead) to
      modulate the photon flux density and a slat collimator to collimate the TCT
      source beam in the axial direction. For the TCT reconstruction, an iterative
      maximum likelihood-expectation maximization algorithm is used that models the
      asymmetric fanbeam geometry. Our initial studies with this system used a 1850 MBq
      (50 mCi) 123mTe line source. The evaluation included TCT scans of a resolution
      phantom, an anthropomorphic thorax phantom and a human subject. For the thorax
      phantom and human subject, short (2-min) and long (14-min) scans were performed.
      The SPECT imaging performance of the fanbeam collimator was also characterized.
      RESULTS: For both phantom and human data, high quality TCT reconstructions were
      obtained with linear attenuation coefficients closely matching narrow beam
      values. In the images of the resolution phantom, the smallest rods (4.8-mm diam)
      were resolved. The long scan images of the thorax phantom and human subject
      demonstrated the high resolution nature of the system and contained no evidence
      of truncation artifacts. With smoothing to control noise, the short scan images
      generally retained the attenuation features of the lung and of soft tissue and
      may provide a practical approach for clinical application. The fanbeam collimator
      demonstrated high resolution SPECT performance. CONCLUSION: These results suggest
      this system may provide an effective and practical approach to TCT imaging for
      nonuniform attenuation correction on a three-headed SPECT camera.

PMID- 9627355
TI  - Procedure guideline for parathyroid scintigraphy. Society of Nuclear Medicine.

PMID- 9627356
TI  - Procedure guideline for hepatic and splenic imaging. Society of Nuclear Medicine.

PMID- 9627357
TI  - Glucose-6-phosphatase activity in the hypothalamus of the ob/ob mouse.
AB  - The hypothalamus and cortex from ob/ob mice and their lean littermates were
      sonicated and then incubated with glucose-6-phosphate (glucose-6-P) and glycerol
      phosphate (glycerol-P). The difference between the rates of hydrolysis of glucose
      6-P and glycerol-P was taken as the measure of glucose-6-phosphatase activity.
      The activity was much higher in the hypothalamus from ob/ob mice versus their
      lean littermates. Activity was undetected in the cortex. These findings raise the
      possibility that a defect in the regulation of glucose-6-phosphatase activity in
      a portion of the hypothalamus may relate to the mechanism underlying obesity in
      the ob/ob mouse. However, obese gene product administration to ob/ob mice, while
      reducing the body weight, did not alter the glucose-6-phosphatase activity.

PMID- 9627358
TI  - Stimulation of 125I-transferrin binding and 59Fe uptake in rat adipocytes by
      vanadate: treatment time determines apparent tissue sensitivity.
AB  - Vanadium compounds have been documented to stimulate a number of insulin
      biological effects in vitro and in vivo. We previously demonstrated stimulation
      of glucose transport and insulin-like growth factor-II (IGF-II) binding in rat
      adipocytes. These actions are associated with translocation of glucose
      transporters and IGF-II receptors from an intracellular compartment to the plasma
      membrane. The transferrin receptor is also recruited to the plasma membrane in
      response to insulin. Freshly isolated rat adipocytes were incubated with vanadate
      and insulin at 37 degrees C, and after treating the cells with KCN to inhibit
      further receptor movement, diferric 125I-transferrin binding was assayed.
      Vanadate stimulated a dose- and time-dependent increase in 125I-transferrin
      binding, reaching maximum (approximately threefold) stimulation at 1 mmol/L after
      a 4-hour incubation. This was equivalent to the maximum insulin effect that was
      obtained with 10(-8) mol/L after 30 minutes. A similar degree of stimulation was
      achieved with 0.1 mmol/L vanadate after 8 hours of exposure. Dose-response data
      showed that the apparent sensitivity to vanadate was time-dependent and increased
      with the duration of exposure (EC50: 30 minutes, 1 mmol/L; 3 hours, 0.35 mmol/L).
      Scatchard analysis of 125I-transferrin binding showed that both insulin and
      vanadate increased receptor binding capacity with no effect on receptor affinity.
      Total cellular transferrin receptor content measured by immunoblotting with
      monoclonal anti-transferrin receptor antibody (OX-26) was not altered by insulin
      or vanadate, consistent with receptor translocation. Assessment of 59Fe uptake
      from 59Fe-labeled diferric transferrin showed that vanadate augmented 59Fe uptake
      in a dose-dependent manner to an extent similar to insulin, demonstrating the
      functional activity of the receptors (percent of control: 10(-8) mol/L insulin,
      175% +/- 23.8%, P < .02; 0.3 mmol/L vanadate, 188% +/- 17.3%, P < .01). We
      conclude that vanadate mimics insulin to augment cell surface transferrin
      receptors and increase Fe uptake in rat adipocytes. The time-dependent apparent
      increase in sensitivity is consistent with the effectiveness of very low
      concentrations of vanadate in vivo after several days of administration, and
      suggests a requirement for vanadate entry into cells to mediate this biological
      response.

PMID- 9627359
TI  - Effect of insulin versus sulfonylurea therapy on cardiovascular risk factors and
      fibrinolysis in type II diabetes.
AB  - In non-insulin-dependent diabetes mellitus (NIDDM), cardiovascular risk factors
      improve during treatment, but whether insulin (I) differs from sulfonylurea (SU)
      therapy is unclear. To separate the contributions of improved diabetic control
      versus treatment regimen to risk factors, we examined the effects of SU and I on
      insulin sensitivity, basal and post-glucose load levels of insulin-like
      molecules, fibrinolysis, and lipid concentrations. Twenty poorly controlled, diet
      treated NIDDM subjects were given I or SU each for a period of 16 weeks in a
      randomized crossover study, with a 4-week washout period between each treatment.
      Subjects were studied at the baselines (B1 and B2) and after each treatment.
      Treatment with I or SU produced similar improvements in glycemia (hemoglobin A1
      [HbA1] B1, 11.7% +/- 2.1%; SU, 8.5% +/- 0.9%; I, 8.6% +/- 1.2%) and the metabolic
      clearance rate of glucose ([MCR-G] B1, 1.86 x/divided by 1.4; SU, 2.36 x/divided
      by 1.4 (P = .005 vB1); I, 2.27 x/divided by 1.4 (P = .07 vB1) ml x kg(-1) x min(
      1)). On SU therapy, subjects had higher fasting and post-glucose load levels of
      intact proinsulin compared with B1 and I (fasting, 13.9 x/divided by 2.6 v 9.5
      x/divided by 2.2 (P = .004) and 9.1 x/divided by 2.4 pmol x L(-1) (P = .01),
      respectively). Plasminogen activator inhibitor-1 (PAI-1) activity and antigen
      were higher than at B1 on SU therapy (23.7 v 19.9 AU x mL(-1) (P = .02) and 47.6
      v 32.2 ng x mL(-1) (P = .006), respectively), but not on I. There were no changes
      compared with B1 and no differences between the two therapies in total, very-low
      density lipoprotein (VLDL), and intermediate-density lipoprotein (IDL)
      cholesterol and triglyceride, low-density lipoprotein (LDL), high-density
      lipoprotein 2 (HDL2) and HDL3 cholesterol, apolipoprotein (apo) A1, A2, and B1,
      or lipoprotein (a) [Lp(a)] levels. In conclusion, (1) treatment with SU or I
      resulted in equal improvement in glycemia and insulin sensitivity, (2) intact
      proinsulin and PAI-1 antigen and activity were higher on SU, and (3) there were
      no differences in lipid concentrations with improved glycemia or between
      therapies.

PMID- 9627360
TI  - Effects of Triton WR 1339 and orotic acid on biliary and serum dolichols in rats.
AB  - Two lysosomal storage diseases, aspartylglucosaminuria and mannosidosis, are
      associated with highly elevated serum dolichol concentrations. To elucidate
      possible mechanisms leading to elevated serum dolichols, we studied the effects
      of Triton WR 1339 (known to increase serum cholesterol) and orotic acid (known to
      decrease serum cholesterol) on blood and biliary dolichol and beta-hexosaminidase
      levels in rats. In Triton WR 1339-treated rats, serum dolichol was markedly
      increased compared with saline-treated controls 1 (400 +/- 70 ng/mL, n = 7 v 85
      +/- 11 ng/mL, n = 8, P < .001), 4 (789 +/- 70 ng/mL, n = 10 v 110 +/- 10 ng/mL, n
      = 7, P < .0001), and 8 (549 +/- 43 ng/mL, n = 8 v 87 +/- 8 ng/mL, n = 7, P <
      .001) days after administration of the drug. By contrast, serum dolichol was
      decreased (64 +/- 5 ng/mL, n = 8 v 119 +/- 7 ng/mL, n = 8, P < .0001) after a 7
      day orotic acid feeding compared with controls. Serum beta-hexosaminidase was
      unaffected by both treatments. Orotic acid also increased biliary dolichol (280
      +/- 47 ng/100 g body weight [BW]/h, n = 7 v 83 +/- 15 ng/100 g BW/h, n = 7, P <
      .01) and beta-hexosaminidase (21 +/- 3 mU/100 g BW/h, n = 7 v 8.3 +/- 2 mU/100 g
      BW/h, n = 9, P < .01) excretion compared with controls. Thus, both Triton WR 1339
      and orotic acid have an effect on dolichol metabolism, and it is conceivable-
      based on our results--that serum dolichol concentrations are regulated, at least
      in part, by a mechanism similar to that for serum cholesterol levels.

PMID- 9627361
TI  - Effects of the peptide HP228 on nerve disorders in diabetic rats.
AB  - Motor and sensory nerve conduction velocities (MNCV and SNCV) were reduced in the
      sciatic nerve of rats after 4 weeks of untreated streptozotocin-induced diabetes,
      and declined further during the following 4 weeks. Treating diabetic rats with
      the novel peptide HP228 had no effect on the decline of MNCV after the first 4
      weeks of diabetes but attenuated the decline in SNCV. HP228 treatment also
      prevented any further decline in MNCV or SNCV between weeks 4 and 8 of diabetes.
      Consequently, at the conclusion of the study, the nerve conduction velocities
      (NCVs) in treated rats were significantly (both P < .001) higher than in
      untreated diabetic rats. Reduced nerve homogenate Na+,K+-adenosine triphosphatase
      (ATPase) activity in diabetic rats was significantly (P < .05) increased by HP228
      but remained significantly (P < .05) lower than in untreated controls. HP228
      treatment also reduced nerve Na+,K+-ATPase activity of control rats compared with
      untreated controls (P < .05). There was no effect of HP228 on the hyperglycemia,
      nerve polyol accumulation, myo-inositol depletion, reduced nerve laser Doppler
      blood flow, thermal hypoalgesia, or reduced mean axonal caliber in diabetic rats
      or on any of these parameters in control rats. These data demonstrate that a
      novel peptide may protect against the slowing of nerve conduction in prolonged
      diabetes and that the mechanism of action is unrelated to aldose reductase
      inhibition, prevention of nerve ischemia, or axonal atrophy. HP228 may prove a
      potential therapeutic agent for the treatment of prolonged diabetic neuropathy.

PMID- 9627362
TI  - The glycolytic pathway to coronary heart disease: a hypothesis.
AB  - Coronary heart disease (CHD) is pathogenetically linked to numerous metabolic
      disturbances. These are inextricably interrelated, constituting identifiable
      clusters or syndromes of cardiovascular risk. Prominent among these is the
      insulin resistance syndrome, whose components, including hyperuricemia, have all
      been linked to CHD pathogenesis. Many mechanisms have been put forward to account
      for the emergence of this syndrome, but none offer a satisfactory explanation for
      the involvement of hyperuricemia. Possible explanations relate to the observation
      of glycolytic disturbances in insulin-resistant and hyperuricemic states. This
      might be expected from the fact that uric acid production is linked to glycolysis
      and that glycolysis is controlled by insulin. Phosphoribosylpyrophosphate (PPRP)
      is an important metabolite in this respect. Its availability depends on ribose-5
      phosphate (R-5-P), the production of which is governed by glycolytic flux.
      Diversion of glycolytic intermediates toward R-5-P, PPRP, and uric acid will
      follow if there is diminished activity of glyceraldehyde-3-phosphate
      dehydrogenase (GA3PDH), which is regulated by insulin. Serum triglyceride
      concentrations may also increase, as might be expected from accumulation of
      glycerol-3-phosphate. Thus, intrinsic defects in GA3PDH and a loss of its
      responsiveness to insulin, by causing accumulation of glycolytic intermediates,
      may explain the association between insulin resistance, hyperuricemia, and
      hypertriglyceridemia. This scenario raises the possibility that disturbances of a
      single glycolytic enzyme may be pivotal in the modulation of metabolic risk
      factors for CHD.

PMID- 9627363
TI  - Nongenetic mouse models of non-insulin-dependent diabetes mellitus.
AB  - The purpose of the study was to develop a mouse model of non-insulin-dependent
      diabetes mellitus (NIDDM) that closely simulates the metabolic abnormalities of
      the human disease and is also cost-effective compared with the genetic models
      currently available. For this purpose, insulin resistance was induced in male
      C57BL/6J or Institute of Cancer Research (ICR) mice by feeding diets enriched in
      either fructose or fat, and hyperglycemia was induced by injecting these mice
      with a dose of streptozotocin (STZ) that does not cause diabetes in chow-fed
      mice. In the case of C57BL/6J mice, insulin levels initially increased in
      response to the fructose- and fat-enriched diets and then decreased to levels
      comparable to or still higher than those in chow-fed mice following STZ
      injection. Associated with the decrease in insulin levels following STZ, fat-fed
      and fructose-fed C57BL/6J mice became significantly hyperglycemic, reaching
      values of 388 +/- 38 and 366 +/- 58 mg/dL, respectively. In contrast, neither
      plasma glucose nor insulin concentrations changed in chow-fed mice injected with
      an identical amount of STZ. Essentially identical findings were seen before and
      after STZ injection in fat-fed compared with chow-fed ICR mice. Although a direct
      comparison was not made, sensitivity to the diabetogenic effects of STZ appeared
      to be greater in fat-fed ICR compared with fat-fed C57BL/6J mice. Finally, plasma
      glucose decreased when mice with these experimental models of NIDDM were treated
      with either metformin or tolbutamide. Given these results, it seems reasonable to
      suggest that the combination of dietary-induced insulin resistance and relatively
      low-dose STZ results in mouse models that should be of use in studying the
      pathophysiology of NIDDM or in evaluating therapeutic compounds for the treatment
      of NIDDM.

PMID- 9627364
TI  - Relationships between phenylalanine hydroxylation and plasma aromatic amino acid
      concentrations in humans.
AB  - We investigated the relationships between phenylalanine hydroxylation (Phe Hy)
      and plasma concentrations of phenylalanine, tyrosine, and glucagon in healthy
      male volunteers (N = 13; age, 29 +/- 3 years). Phe Hy, as well as the Phe and Tyr
      rate of appearance (Ra), were measured during L-[2H5]-Phe and L-[2H2]-Tyr
      continuous intravenous (i.v.) infusions both under basal postabsorptive
      conditions (N = 13) and following divergent changes of plasma aromatic amino
      acids (AAA) concentrations. Namely, AAA were increased by administration of a
      balanced synthetic mixed meal (n = 6) or selectively decreased by i.v. infusion
      of insulin along with a Phe-deficient, Tyr and tryptophan-deprived amino acid
      mixture ([IAA] n = 7). Following the meal, plasma Phe (54 +/- 3 to 81 +/- 12
      micromol/L), plasma Tyr (54 +/- 4 to 91 +/- 7), Phe Hy (0.09 +/- 0.01 to 0.15 +/-
      0.02 micromol/kg x min), Phe Ra (0.65 +/- 0.04 to 0.96 +/- 0.07), and Tyr Ra
      (0.51 +/- 0.03 to 0.93 +/- 0.11) all significantly increased (P < or = .05 v
      basal). IAA infusion significantly decreased plasma Phe (to 47 +/- 3 micromol/L),
      plasma Tyr (to 25 +/- 4), Phe Hy (to 0.07 +/- 0.004 micromol/kg x min), and Tyr
      Ra (to 0.29 +/- 0.02; all P < or = .05 v sal), while Phe Ra did not change (0.64
      +/- 0.04, NS). Plasma glucagon did not change in the three experimental periods
      (basal, 85 +/- 7; meal, 72 +/- 10; IAA, 92 +/- 14 pg/mL; NS). Using linear
      regression analysis, plasma Phe was positively related to both Phe Hy (R2 = .76,
      P < .001) and plasma Tyr (R2 = .80, P < .001); Phe Hy and plasma Tyr were also
      significantly correlated (R2 = .60, P < .001). No correlation was found between
      Phe Hy and basal plasma glucagon (R2 = .04, NS). Using multiple regression
      analysis with plasma Tyr as the dependent variable, plasma Phe was still
      correlation with plasma Tyr (t = 4.29, P = .0002), while the relationship between
      Phe Hy and plasma Tyr was no longer significant (t = 0.69, P = .49). These data
      indicate that plasma Phe is closely associated with its own hydroxylative
      disposal in humans, and confirm that Phe conversion to Tyr may play a
      physiological role in maintaining balanced plasma phenylalanine and tyrosine
      concentrations.

PMID- 9627365
TI  - Estrogen replacement decreases the level of antibodies against oxidized low
      density lipoprotein in postmenopausal women with coronary heart disease.
AB  - The effect of estrogen replacement therapy (ERT) on plasma lipid concentrations
      and oxidation parameters was studied in 25 hypercholesterolemic women with
      coronary heart disease (CHD). During ERT, the low-density lipoprotein cholesterol
      (LDLc) concentration decreased from 4.31 +/- 0.72 to 3.85 +/- 0.62 mmol/L (P <
      .01) and high-density lipoprotein cholesterol (HDLc) increased from 1.42 +/- 0.30
      to 1.55 +/- 0.33 mmol/L (P < .01). The concentration of autoantibodies against
      oxidized LDL decreased from 25.9 +/- 22.0 to 22.7 +/- 19.9 mg/L (P < .05),
      indicating that ERT may have antioxidative effects in vivo. The lag time to
      oxidation and the LDL subclass pattern did not change. Analysis of the influence
      of smoking on the efficacy of ERT showed that ERT significantly affected LDLc and
      HDLc concentrations in 15 nonsmoking women. However, in 10 cigarette smokers, no
      significant changes in LDLc or HDLc levels were observed. Smoking did not affect
      the concentration of autoantibodies to oxidized LDL or the lag time.
      Medroxyprogesterone acetate ([MPA] 10 mg daily) added to ERT decreased HDLc by 9%
      (P < .01) but did not affect the LDLc level, LDL subclass pattern, or lag time.
      In conclusion, ERT may have antioxidative effects in vivo and favorably affects
      dyslipidemia in hypercholesterolemic women with CHD, especially when they refrain
      from smoking.

PMID- 9627366
TI  - Leucine metabolism in rat liver after a bolus injection of endotoxin.
AB  - To evaluate the contribution of hepatic tissue to alterations in the metabolism
      of proteins and the branched-chain amino acids (BCAA) leucine, isoleucine, and
      valine in systemic inflammatory response syndrome, we studied the changes of
      leucine metabolism in isolated perfused liver (IPL) of endotoxin-treated rats.
      Male albino rats were injected with the endotoxin of Salmonella enteritidis (5 mg
      x kg(-1)) or saline (control). Four hours later, leucine and ketoisocaproate
      (KIC) oxidation and incorporation into liver proteins were determined in IPL
      using the single-pass liver perfusion technique. L-[1-(14)C]leucine and alpha
      keto[1-(14)C]isocaproic acid were used as a tracer in two separate experiments.
      Endotoxin treatment resulted in a decrease of plasma BCAA levels, an increase of
      leucine oxidation, and a decrease of KIC oxidation by IPL. Leucine incorporation
      into liver proteins was lower in endotoxin-treated rats, and we did not find
      measurable incorporation of the labeled carbon of KIC in liver proteins in either
      group of animals. The sum of individual amino acid concentrations in the effluent
      perfusate was higher in endotoxin-treated animals, although only leucine and
      phenylalanine increased significantly. The decrease in KIC oxidation indicates a
      decreased capacity of hepatic tissue to oxidize branched-chain ketoacids (BCKA).
      The increase in leucine oxidation by IPL of endotoxin-treated rats indicates an
      increase in BCAA aminotransferase activity. These changes demonstrate an
      important response of the body that enables the resynthesis of essential BCAA
      from their ketoanalogs delivered to the liver from peripheral tissues,
      particularly muscle.

PMID- 9627367
TI  - Plasma homocysteine concentrations are regulated by acute hyperinsulinemia in
      nondiabetic but not type 2 diabetic subjects.
AB  - An association between hyperhomocysteinemia and premature atherosclerosis in
      patients with non-insulin-dependent diabetes mellitus (NIDDM) has recently been
      described. Little is known about the role of insulin in homocysteine [H(e)]
      metabolism. We measured plasma H(e) concentrations in the fasting state and
      during a hyperinsulinemic-euglycemic clamp in normal subjects and patients with
      NIDDM. Plasma H(e) decreased significantly from 7.2 +/- 2.6 to 6.0 +/- 2.7 mmol/L
      (P < .01) in normal subjects, but did not change in patients with NIDDM (6.0 +/-
      2.7 to 5.9 +/- 2.5 mmol/L, respectively). These data suggest that plasma H(e)
      concentrations are regulated by acute hyperinsulinemia in normal subjects, but
      not in insulin-resistant NIDDM subjects. These abnormalities may have
      implications for the pathogenesis of premature vascular disease associated with
      NIDDM.

PMID- 9627368
TI  - Twenty-four-hour urinary free cortisol in patients with acquired immunodeficiency
      syndrome.
AB  - Many patients with acquired immune deficiency syndrome (AIDS) have symptoms
      consistent with adrenal insufficiency, but only a small subset of these patients
      meet criteria for adrenal insufficiency during a short corticotropin (ACTH)
      stimulation test. We hypothesized that patients with AIDS and symptoms of adrenal
      insufficiency who produce normal amounts of cortisol in response to
      administration of 0.25 mg cosyntropin may nevertheless produce lower amounts of
      cortisol in a course of 24 hours than comparably sick AIDS patients without
      symptoms of adrenal insufficiency or comparably sick patients without AIDS. We
      studied four groups of male patients: AIDS patients with symptoms suggestive of
      adrenal insufficiency but with a normal response to cosyntropin (group I), AIDS
      patients without symptoms suggestive of adrenal insufficiency (group II), human
      immunodeficiency virus (HIV)-negative patients with serious acute or chronic
      illness (group III), and healthy subjects (group IV). The following variables
      were examined: age, CD4 cell count, Acute Physiologic and Chronic Health
      Evaluation (APACHE) score, serum cortisol and plasma ACTH at baseline; serum
      cortisol at 30 and 60 minutes after intravenous administration of 0.25 mg
      cosyntropin; and 24-hour urinary free cortisol. The four groups had a similar
      mean age and baseline plasma ACTH and serum cortisol levels. However, a change in
      cortisol from baseline to 30 and 60 minutes after administration of cosyntropin
      was significantly smaller in both groups of AIDS patients than in the sick
      patients without AIDS and normal subjects. There were also differences noted
      between the two groups of AIDS patients: both baseline and stimulated levels of
      cortisol tended to correlate directly with ACTH levels in patients without
      symptoms of adrenal insufficiency, while this relationship appeared to be inverse
      in patients with symptoms suggestive of adrenal insufficiency (r = -.57 to -.7, P
      < .05 to .14). The 24-hour urinary free cortisol levels were similar among all
      groups, but correlated strongly with baseline and stimulated serum cortisol
      levels only in patients with AIDS and symptoms of adrenal insufficiency (r = .8
      to .9, P < .002 to .015). We conclude that (1) AIDS patients with and without
      symptoms of adrenal insufficiency may have either normal adrenal function or
      somewhat suboptimal adrenal reserve as demonstrated by a blunted cortisol
      response during the short ACTH stimulation test in comparison to HIV-negative
      comparably sick patients or healthy subjects; and (2) 24-hour urinary free
      cortisol is not a useful test for detection of subtle abnormalities of adrenal
      function in patients with AIDS.

PMID- 9627369
TI  - Effect of glucagon on the plasma concentration of uridine.
AB  - To determine whether glucagon affects the plasma concentration of uridine, we
      administered 100 mL physiological saline containing 1 mg glucagon or 100 mL
      physiological saline alone intravenously over 1 hour to healthy subjects.
      Glucagon decreased the plasma concentration of uridine from 5.72 +/- 1.05 to 4.80
      +/- 0.60 micromol/L but increased the concentrations of cyclic adenosine
      monophosphate (cAMP) in plasma and pyruvic acid and lactic acid in blood 59-, 1.4
      , and 1.3-fold, respectively. Although glucagon increased urinary excretion of
      uric acid, it did not affect the plasma concentration of purine bases
      (hypoxanthine, xanthine, and uric acid) or urinary excretion of oxypurines and
      uridine, indicating that glucagon does not affect purine degradation and
      suggesting that glucagon does not affect adenosine triphosphate (ATP) consumption
      induced pyrimidine degradation. In contrast, physiological saline did not affect
      any of the measured variables. These results suggest that glucagon enhanced Na+
      dependent uridine uptake from the blood into the cells, since glucagon stimulates
      Na+-dependent uridine uptake into cells in vitro.

PMID- 9627370
TI  - A cross-sectional evaluation of spontaneous platelet aggregation in relation to
      complications in patients with type II diabetes mellitus.
AB  - To clarify the relationship between platelet function and diabetic complications,
      we investigated spontaneous platelet aggregation (SPA) and agonist-induced
      platelet aggregation by a particle counting method using light scattering (LS)
      and by a conventional light transmission method (LT) in 23 age- and sex-matched
      control subjects and 74 patients with type II diabetes mellitus. We also observed
      platelets using the FIC-2 (TOA Medical Electronics, Kobe, Japan) flow cytometer
      and imaging device. Observation by the FIC-2 device showed microaggregates of
      platelets in samples with increased SPA-LS. SPA-LS was significantly elevated in
      patients with type II diabetes mellitus as a whole compared with control
      subjects. SPA-LS also showed significant differences between control subjects and
      three diabetic patient subgroups with a varying severity of retinopathy,
      nephropathy, or neuropathy, and the mean values increased along with the
      increasing severity of complications. On the other hand, although SPA-LT also
      showed significant differences between these groups, the absolute values were all
      less than 10%, which we believe does not warrant quantitative analysis. Adenosine
      5'-diphosphate (ADP)-induced platelet aggregation failed to show significant
      differences between controls and subjects with a varying severity of retinopathy
      by either LS or LT, which indicates that SPA is more sensitive than agonist
      induced platelet aggregation in relation to diabetic complications. We observed
      significant correlations between SPA-LS and the patients' age, hemoglobin A1c
      (HbA1c) level, plasma fibrinogen level, or 6-keto-PGF1alpha (6KF) to 11-dehydro
      thromboxane B2 (TXB2) ratio. Our study demonstrated a close relationship between
      platelet hyperaggregability and diabetic complications, and a longitudinal
      prospective study of SPA-LS in diabetic patients is warranted to clarify cause
      and-effect relationships.

PMID- 9627371
TI  - Improved accuracy and precision of gas chromatography/mass spectrometry
      measurements for metabolic tracers.
AB  - The use of stable-isotope tracer methodology to study substrate metabolic
      kinetics requires accurate measurement of the tracer to tracee ratio (TTR), often
      by gas chromatography/mass spectrometry (GC/MS). Many approaches for measurement
      of the TTR by GC/MS do not use standards of known isotopic enrichment to control
      for variability in instrument response. In addition, most GC/MS applications
      exhibit some degree of concentration dependency whereby the measured ion
      abundance ratio varies with the quantity of sample analyzed, thereby placing a
      limitation on the accuracy of isotopic enrichment standard curves unless the
      quantities of standards and samples analyzed are closely matched. We document the
      degree to which day-to-day variability can affect the instrument response for
      several GC/MS analyses of metabolic tracers when isotopic enrichment standards
      are not used to control for variable instrument response. Furthermore, we report
      a new approach that incorporates concentration dependencies within a standard
      curve to improve the accuracy and precision of TTR measurements over a range of
      sample quantities analyzed. The new approach was applied to plasma samples
      obtained from experimental protocols performed in human subjects with three
      commonly used tracers: 2H2-palmitate, 15N2-urea, and 13C-leucine. Variability in
      the day-to-day instrument response was 84% and 26% for 2H2-palmitate and 15N2
      urea, respectively; in addition, up to 10% variability due to concentration
      dependency was noted for these applications. The new approach virtually
      eliminated these sources of variability. After controlling for concentration
      dependency, a threefold reduction in the standard error was noted when the
      enrichment of 13C-leucine measured by electron-impact (EI) ionization GC/MS was
      correlated against negative chemical ionization (NCI) GC/MS. These data
      demonstrate that our new approach decreases the errors in TTR determination
      caused by variations in instrument response and concentration dependency. This
      approach is generically applicable, and can improve the accuracy and precision of
      TTR determinations for most GC/MS analyses.

PMID- 9627372
TI  - Glucagon increases glutamine uptake without affecting glutamine release in
      humans.
AB  - Glucagon causes transient hyperglycemia and persistent hypoaminoacidemia, but the
      mechanisms of this action are unclear. To address this question, the present
      study measured the effects of glucagon on glucose, leucine, phenylalanine, and
      glutamine kinetics. Seven healthy subjects each underwent three pancreatic clamp
      studies (octreotide 30 ng/kg/min, insulin 0.15 mU/kg/min, and glucagon 1.4
      ng/kg/min) lasting 7 hours. During the last 3.5 hours of the studies, glucagon
      infusion was either unchanged (study 0) or increased to 4 and 7 ng/kg/min
      (studies 1 and 2). The higher glucagon infusion rates increased the glucagon
      concentration by 50% and 100%, respectively. [6,6-(2)H2]glucose, [2
      (15)N]glutamine, 2H5-phenylalanine, and 2H3-leucine were infused to quantify the
      respective fluxes. Glucagon transiently increased glucose concentrations by
      stimulating glucose production, which peaked in 15 minutes to 3.82 +/- 0.36 and
      4.21 +/- 0.33 mg/kg/min in studies 1 and 2 and then returned to the
      postabsorptive levels. Glucagon decreased the glutamine concentration (-10% +/-
      2% and -22% +/- 2% in studies 1 and 2 v study 0, P < .05), because glutamine
      uptake became greater than glutamine release (balance from -1.9 +/- 0.9 in study
      0 to -8.1 +/- 1.1 and -13.6 +/- 1.0 micromol/kg/h in studies 1 and 2, P < .01).
      Glucagon decreased the leucine concentration (-11% +/- 3% in study 2 v study 0, P
      < .02) and caused a small increment in proteolysis (+6% in study 2 v study 0, P <
      .01) that was related to the decrement in glutamine concentrations. Phenylalanine
      kinetics were not significantly affected. These results show that glucagon
      promotes the uptake of gluconeogenic substrates but does not increase their
      release, suggesting that glucagon-induced hyperglycemia is short-lived because
      glucagon fails to provide more fuel for gluconeogenesis. The small increase in
      proteolysis and the depletion of circulating glutamine prove that physiologic
      hyperglucagonemia can contribute to protein catabolism.

PMID- 9627373
TI  - High-monounsaturated fat diet-induced obesity and diabetes in C57BL/6J mice.
AB  - A high-monounsaturated fat diet has been proposed as a palatable alternative to a
      high-carbohydrate diet in diabetic patients, but it is unknown whether a higher
      intake of monounsaturated fat induces obesity and diabetes, as usually observed
      with other types of fat. To answer this question, C57BL/6J mice were divided into
      three groups: the first group was given a high-carbohydrate diet, and the other
      two groups were given a high-monounsaturated fat diet (60% of total energy) as
      olive oil or synthetic triolein for 4 months. It has been previously reported
      that the C57BL/6J mouse has a genetic predisposition for intraabdominal obesity
      and non-insulin-dependent diabetes mellitus (NIDDM) by high-polyunsaturated fat
      (n-6) feeding. Although there were no significant differences in energy intake
      and fat absorption among these three groups, compared with the high-carbohydrate
      diet, both high-monounsaturated fat diets produced hyperglycemia, obesity, and
      triglyceride accumulation in the liver and skeletal muscle. These data indicate
      that the recently recommended high-monounsaturated fat diet might induce obesity
      and diabetes.

PMID- 9627374
TI  - Effect of dietary lipids on hepatic and extrahepatic sterol 27-hydroxylase
      activity in high- and low-responding baboons.
AB  - Our previous studies found that low low-density lipoprotein (LDL)-responding
      baboons compared with high LDL-responding baboons have higher hepatic sterol 27
      hydroxylase activity when consuming a high-cholesterol and high-fat (HCHF) diet.
      The present studies were conducted to determine whether the extrahepatic activity
      of sterol 27-hydroxylase is also higher in low-responding baboons and to assess
      whether the enzyme is regulated at the protein level. We measured the hepatic
      sterol 27-hydroxylase activity and protein level and plasma 27-hydroxycholesterol
      concentration in six low- and six high-responding baboons on both the basal and
      the HCHF diet. We also compared the sterol 27-hydroxylase activity in the adrenal
      gland and 27-hydroxycholesterol concentration in blood lymphocytes from high- and
      low-responding baboons consuming the HCHF diet. With the HCHF diet, the plasma 27
      hydroxycholesterol concentration and hepatic sterol 27-hydroxylase activity and
      protein level increased rapidly in low responders, but not in high responders.
      Blood lymphocytes of low-responding baboons cultured in the presence of
      lipoprotein-deficient serum (LPDS) had lower cholesterol concentrations than
      those from high-responding baboons. Addition of exogenous 27-hydroxycholesterol
      to the culture medium of blood lymphocytes decreased the cellular cholesterol
      concentration. Plasma 27-hydroxycholesterol and hepatic sterol 27-hydroxylase
      activity and protein levels were negatively correlated with the plasma VLDL + LDL
      cholesterol concentration and VLDL + LDL/HDL cholesterol ratio after 6 weeks on
      the HCHF diet, but not on the chow diet. The results suggest that sterol 27
      hydroxylase activity in both hepatic and extrahepatic tissues attenuates the
      dietary responsiveness in baboons, and the enzyme activity is not regulated by
      the specific activity of the protein.

PMID- 9627375
TI  - Xylitol-induced increase in the plasma concentration and urinary excretion of
      uridine and purine bases.
AB  - To determine whether xylitol increases the plasma concentration and urinary
      excretion of uridine together with purine bases, we administered xylitol (0.6
      g/kg weight) intravenously to six normal subjects using a 10% xylitol solution.
      Xylitol infusion increased the plasma concentration and urinary excretion of
      uridine, as well as purine bases, while it decreased both the concentrations of
      inorganic phosphate in plasma and pyruvic acid in blood and increased the blood
      concentration of lactic acid. These results suggest that an increase in the
      plasma concentration and urinary excretion of uridine is ascribable to increased
      pyrimidine degradation following purine degradation induced by xylitol.

PMID- 9627376
TI  - Fat-modified diets influence serum concentrations of cholesterol precursors and
      plant sterols in hypercholesterolemic subjects.
AB  - Serum noncholesterol sterols, cholesterol precursors and plant sterols, are
      indicators of cholesterol absorption and synthesis. Serum plant sterol
      concentrations correlate positively with cholesterol absorption, but have also
      been found to correlate with dietary unsaturated to saturated fatty acid ratios.
      We studied the concentration of serum noncholesterol sterols during four
      different fat-modified diets, (1) high-fat, saturated fat-enriched (control), (2)
      reduced-fat, sunflower oil-enriched (SO-enriched), (3) rapeseed oil-enriched (RO
      enriched), and (4) reduced-fat, saturated fat-enriched (reduced-fat), followed
      for 6 months in hypercholesterolemic subjects in a parallel design. The
      proportion of lathosterol (micrograms per 100 mg cholesterol), a precursor of
      cholesterol synthesis, increased significantly (P < .05) in both SO-enriched
      (mean +/- SD 147 +/- 57 v 167 +/- 76, 0 v 6 months) and RO-enriched (147 +/- 54 v
      157 +/- 52) groups, where the reduction in low-density lipoprotein (LDL)
      cholesterol was also significant. The proportion of sitosterol, a plant sterol,
      decreased significantly in the control group (137 +/- 48 v 122 +/- 42), and the
      proportion of another plant sterol, campesterol, increased in the RO-enriched
      group (280 +/- 141 v 333 +/- 162), reflecting changes in the use of vegetable
      oils in these two groups rather than increased cholesterol absorption. In the
      whole study population, the proportion of linoleic and alpha-linolenic acid (a
      marker of the use of RO) in cholesterol esters (CEs) correlated (P < .001) with
      the proportion of sitosterol (r = .43) and campesterol (r = .36) in serum at the
      end of the study. In conclusion, serum cholesterol precursors were found to be
      useful indicators of cholesterol metabolism, but changes in serum plant sterols
      reflected dietary changes rather than cholesterol metabolism during long-term
      dietary intervention with fat-modified diets.

PMID- 9627377
TI  - Short-term administration of tall oil phytosterols improves plasma lipid profiles
      in subjects with different cholesterol levels.
AB  - To assess the short-term cholesterol-lowering potential of sitostanol-containing
      tall oil plant sterols, 22 subjects consumed fixed-food diets over two 10-day
      periods with or without 21.2 mg/kg body weight/d tall oil phytosterols
      (sitosterol 62%, sitostanol 21%, campesterol 16%, and campestanol 1%) in a
      randomized crossover study design. On day 10 of each diet, plasma lipoprotein
      cholesterol levels, plasma phytosterol concentrations, and cholesterol
      biosynthesis rates were determined. Total cholesterol (TC) and low-density
      lipoprotein (LDL) cholesterol levels were lower (P < .01) after administration of
      tall oil phytosterol (4.7 +/- 0.3 and 3.0 +/- 0.3 mmol/L, respectively) versus
      placebo (5.0 +/- 0.3 and 3.2 +/- 0.3 mmol/L, respectively). Tall oil treatment
      had no effect on the plasma high-density lipoprotein (HDL) cholesterol level (1.1
      +/- 0.1 mmol/L) versus placebo (1.1 +/- 0.1 mmol/L). Similarly, plasma
      triglyceride (TG) levels did not differ between tall oil (1.3 +/- 0.2 mmol/L) and
      placebo (1.4 +/- 0.2 mmol/L) treatments. Plasma campesterol (15.8 +/- 3.7
      mmol/mol cholesterol) and sitosterol (6.0 +/- 2.1 mmol/mol cholesterol) levels
      were not different after tall oil treatment versus placebo treatment (15.4 +/-
      2.3 and 6.4 +/- 2.0 mmol/mol cholesterol, respectively). Plasma sitostanol levels
      were essentially undetectable. No difference was observed in cholesterol
      biosynthesis between tall oil (0.045 +/- 0.004 pools/d) and placebo (0.034 +/-
      0.004 pools/d) treatments; however, the effect of treatments in subjects with
      different cholesterol levels varied. In subjects with lower cholesterol values,
      the red blood cell cholesterol fractional synthesis rate (FSR) increased from
      0.0291 +/- 0.0054 pools/d after placebo to 0.0509 +/- 0.0049 pools/d (P < .05)
      after phytosterol treatment. In subjects with higher cholesterol values, the red
      blood cell cholesterol FSR did not change significantly after treatment. These
      results demonstrate the short-term efficacy of tall oil plant sterols as
      cholesterol-lowering agents.

PMID- 9627378
TI  - Distribution and correlates of serum high-density lipoprotein subclasses (LpA-I
      and LpA-I:A-II) in children from a biracial community. The Bogalusa Heart Study.
AB  - High-density lipoprotein (HDL) subclasses are considered to differ in terms of
      antiatherogenic potential. Therefore, the distribution and correlates of serum
      lipoprotein A-I (LpA-I) and LpA-I:A-II were examined in a random community-based
      subsample of black (n = 1,021) and white (n = 1,087) children aged 5 to 17 years.
      Black children had significantly higher LpA-I levels than white children. With
      respect to LpA-I:A-II, prepubertal (age 5 to 10 years) black males and pubertal
      (age 11 to 17 years) white children showed significantly higher values than their
      counterparts. With the exception of the LpA-I:A-II difference among prepubertal
      males, the observed black-white difference was independent of the racial
      differential in serum triglycerides, a metabolic correlate of HDL. A significant
      sex differential (males > females) was noted among blacks and whites for both HDL
      subclasses, with the exception of LpA-I levels at the pubertal age. Among the
      pubertal age group, a male-female crossover trend (females > males) in LpA-I
      levels was apparent after age 14. Sexual maturation and age were the major
      factors (negative) contributing to the variability in the levels of HDL
      subclasses among race-sex groups; adiposity (negative), insulin (negative),
      alcohol intake (positive), and oral contraceptive use (positive) emerged as minor
      but significant predictor variables. In terms of a relation to other lipoprotein
      variables, LpA-I compared with LpA-I:A-II correlated much more strongly with HDL
      cholesterol. Unlike LpA-I, LpA-I:A-II was associated significantly (positively)
      with low-density lipoprotein (LDL) cholesterol. These findings are indicative of
      intrinsic metabolic differences among the race-sex groups early in life,
      resulting in variability in the HDL subclass pattern and attendant
      antiatherogenic potential.

PMID- 9627379
TI  - Yeast adaptation on softwood prehydrolysate.
AB  - Several strains and genera of yeast, including Saccharomyces cerevisiae D5A,
      Pachysolen tannophilus, S. cerevisiae K-1, Brettanomyces custersii, Candida
      shehatae, and Candida acidothermophilum, are screened for growth on dilute acid
      pretreated softwood prehydrolysate. Selected softwood species found in forest
      underbrush of the western United States, which contain predominantly hexosan
      hemicellulose, were studied. This phase of the work emphasized debarked Douglas
      fir. The two best initial isolates were gradually selected for improved growth by
      adaptation to increasing prehydrolysate concentrations in batch culture, with due
      consideration of nutrient requirements. Microaerophilic conditions were evaluated
      to encourage tolerance of pretreatment hydrolysate, as well as ethanol product.
      Adaptation and simultaneous saccharification and fermentation (SSF) results are
      used to illustrate improved performance with an adapted strain, compared to the
      wild type.

PMID- 9627380
TI  - Improving fermentation performance of recombinant Zymomonas in acetic acid
      containing media.
AB  - In the production of ethanol from lignocellulosic biomass, the hydrolysis of the
      acetylated pentosans in hemicellulose during pretreatment produces acetic acid in
      the prehydrolysate. The National Renewable Energy Laboratory (NREL) is currently
      investigating a simultaneous saccharification and cofermentation (SSCF) process
      that uses a proprietary metabolically engineered strain of Zymomonas mobilis that
      can coferment glucose and xylose. Acetic acid toxicity represents a major
      limitation to bioconversion, and cost-effective means of reducing the inhibitory
      effects of acetic acid represent an opportunity for significant increased
      productivity and reduced cost of producing fermentation fuel ethanol from
      biomass. In this study, the fermentation performance of recombinant Z. mobilis
      39676:pZB4L, using a synthetic hardwood prehydrolysate containing 1% (w/v) yeast
      extract, 0.2% KH2PO4, 4% (w/v) xylose, and 0.8% (w/v) glucose, with varying
      amounts of acetic acid was examine. To minimize the concentration of the
      inhibitory undissociated form of acetic acid, the pH was controlled at 6.0. The
      final cell mass concentration decreased linearly with increasing level of acetic
      acid over the range 0-0.75% (w/v), with a 50% reduction at about 0.5% (w/v)
      acetic acid. The conversion efficiency was relatively unaffected, decreasing from
      98 to 92%. In the absence of acetic acid, batch fermentations were complete at 24
      h. In a batch fermentation with 0.75% (w/v) acetic acid, about two-thirds of the
      xylose was not metabolized after 48 h. In batch fermentations with 0.75% (w/v)
      acetic acid, increasing the initial glucose concentration did not have an
      enhancing effect on the rate of xylose fermentation. However, nearly complete
      xylose fermentation was achieved in 48h when the bioreactor was fed glucose. In
      the fed-batch system, the rate of glucose feeding (0.5 g/h) was designed to
      simulate the rate of cellulolytic digestion that had been observed in a modeled
      SSCF process with recombinant Zymomonas. In the absence of acetic acid, this rate
      of glucose feeding did not inhibit xylose utilization. It is concluded that the
      inhibitory effect of acetic acid on xylose utilization in the SSCF biomass-to
      ethanol process will be partially ameliorated because of the simultaneous
      saccharification of the cellulose.

PMID- 9627381
TI  - Conditions that promote production of lactic acid by Zymomonas mobilis in batch
      and continuous culture.
AB  - This study documents the similar pH-dependent shift in pyruvate metabolism
      exhibited by Zymomonas mobilis ATCC 29191 and ATCC 39676 in response to
      controlled changes in their steady-state growth environments. The usual high
      degree of ethanol selectivity associated with glucose fermentation by Z. mobilis
      is associated with conditions that promote rapid and robust growth, with about
      95% of the substrate (5% w/v glucose) being converted to ethanol and C)2, and the
      remaining 5% being used for the synthesis of cell mass. Conditions that promote
      energetic uncoupling cause the conversion efficiency to increase to 98% as a
      result of the reduction in growth yield (cell mass production). Under conditions
      of glucose-limited growth in a chemostat, with the pH controlled at 6.0, the
      conversion efficiency was observed to decrease from 95% at a specific growth rate
      of 0.2/h to only 80% at 0.042/h. The decrease in ethanol yield was solely
      attributable to the pH-dependent shift in pyruvate metabolism, resulting in the
      production of lactic acid as a fermentation byproduct. At a dilution rate (D) of
      0.042/h, decreasing from pH 6.0 to 5.5 resulted in a decrease in lactic acid from
      10.8 to 7.5 g/L. Lactic acid synthesis depended on the presence of yeast extract
      (YE) or tryptone in the 5% (w/v) glucose-mineral salts medium. At D = 0.15/h,
      reduction in the level of YE from 3 to 1 g/L caused a threefold decrease in the
      steady-state concentration of lactic acid at pH 6. No lactic acid was produced
      with the same mineral salts medium, with ammonium chloride as the sole source of
      assimilable nitrogen. With the defined salts medium, the conversion efficiency
      was 98% of theoretical maximum. When chemostat cultures were used as seed for pH
      stat batch fermentations, the amount of lactic acid produced correlated well with
      the activity of the chemostat culture; however, the mechanism of this prolonged
      induction effect is unknown. The levels of lactic acid produced by Z. mobilis in
      this study have not been previously reported. Zymomonas is Gram-negative, and at
      no time did microscopic inspection of lactic-acid-producing cultures indicate the
      presence of Gram-positive organisms. Although these observations are very
      preliminary in nature, they have implications for the regulation of glycolytic
      flux in Zymomonas, and demonstrate the possibility of an alternative fate for
      pyruvate previously presumed not to exits.

PMID- 9627382
TI  - A novel fermentation pathway in an Escherichia coli mutant producing succinic
      acid, acetic acid, and ethanol.
AB  - Escherichia coli strain NZN111, which is unable to grow fermentatively because of
      insertional inactivation of the genes encoding pyruvate: formate lyase and the
      fermentative lactate dehydrogenase, gave rise spontaneously to a chromosomal
      mutation that restored its ability to ferment glucose. The mutant strain, named
      AFP111, fermented glucose more slowly than did its wild-type ancestor, strain
      W1485, and generated a very different spectrum of products. AFP111 produced
      succinic acid, acetic acid, and ethanol in proportions of approx 2:1:1.
      Calculations of carbon and electron balances accounted fully for the observed
      products; 1 mol of glucose was converted to 1 mol of succinic acid and 0.5 mol
      each of acetic acid and ethanol. The data support the emergence in E. coli of a
      novel succinic acid:acetic acid:ethanol fermentation pathway.

PMID- 9627383
TI  - Isolation, identification, and keratinolytic activity of several feather
      degrading bacterial isolates.
AB  - Several feather-degrading bacterial isolates were isolated from Egyptian soil.
      These isolates were able to degrade chicken feather, when grown on basal medium
      containing 1% native feather as a source of energy, carbon, and nitrogen. Feather
      waste, generated in large quantities as a byproduct of commercial poultry
      processing, is nearly pure keratin, which is not easily degradable by common
      proteolytic enzymes. The isolates were identified according to the morphological
      characteristics, biochemical tests, and API 50 CHB Bacillus system. Proteolytic
      and keratinolytic activities of these isolates were monitored throughout the
      cultivation of the bacterial isolates on feather. Resulting soluble proteins,
      which were released as a result of the biodegradation of feather, were
      demonstrated by SDS-PAGE.

PMID- 9627384
TI  - Use of hemicellulose hydrolysate for beta-glucosidase fermentation.
AB  - Hydrolysis of cellulose by Trichoderma cellulases often results in a mixture of
      glucose, cellobiose, and low-mol-wt cellodextrins. Cellobiose is nonfermentable
      for most yeasts, and therefore it has to be hydrolyzed to glucose by beta
      glucosidase prior to ethanol fermentation. In the present study, the beta
      glucosidase production of one Penicillium and three Aspergillus strains, which
      were previously selected out of 24 strains, was investigated on steam pretreated
      willow. Both steam-pretreated willow and hemicellulose hydrolysate, released
      during steam explosion of willow, were used as carbon sources. Reference
      cultivation runs were performed using prehydrolyzed Solka Floc and glucose. The
      four strains were compared with Trichoderma reesei regarding sugar consumption
      and beta-glucosidase production. Aspergillus niger and Aspergillus phoenicis
      proved to be the best enzyme producers on hemicellulose hydrolysate. The maximum
      beta-glucosidase activity, 4.60 IU/mL, was obtained when A. phoenicis was
      cultivated on the mixture of hemicellulose hydrolysate and steam-pretreated
      willow. The maximum yield of enzyme activity, 502 IU/g total carbohydrate, was
      obtained when Aspergillus foetidus was cultivated on the hemicellulose
      hydrolysate.

PMID- 9627385
TI  - Production of a novel pyranose 2-oxidase by basidiomycete Trametes multicolor.
AB  - During a screening for the enzyme pyranose 2-oxidase (P2O) which has a great
      potential as a biocatalyst for carbohydrate transformations, Trametes multicolor
      was identified as a promising, not-yet-described producer of this particular
      enzyme activity. Furthermore, it was found in this screening that the enzyme
      frequently occurs in basidiomycetes. Intracellular P2O was produced in a growth
      associated manner by T. multicolor during growth on various substrates, including
      mono-, oligo-, and polysaccharides. Highest levels of this enzyme activity were
      formed when lactose or whey were used as substrates. Peptones from casein and
      other casein hydrolysates were found to be the most favorable nitrogen sources
      for the formation of P2O. By applying an appropriate feeding strategy for the
      substrate lactose, which ensured an elevated concentration of the carbon source
      during the entire cultivation, levels of P2O activity obtained in laboratory
      fermentations, as well as the productivity of these bioprocess experiments, could
      be enhanced more than 2.5-fold.

PMID- 9627386
TI  - Broad spectrum and mode of action of an antibiotic produced by Scytonema sp.
      TISTR 8208 in a seaweed-type bioreactor.
AB  - A photobioreactor was constructed using anchored polyurethane foam strips (1 x 1
      x 40 cm) fixed onto a stainless-steel ring to prevent flotation, as a biomass
      support material (BSM). This type of reactor was named a seaweed-type bioreactor.
      A filamentous cyanobacterium, Scytonema sp. TISTR 8208, which produces a novel
      cyclic dodecapeptide antibiotic, was immobilized in seaweed-type photobioreactor
      and cultivated with air containing 5% CO2 sparged at a gas flow rate of 250
      mL/min under illumination at a light intensity of 200 mmol photon m-2 s-1. The
      antibiotic produced in the seaweed-type photobioreactor was purified by HPLC and
      examined regarding its spectrum and mode of action. The antibiotic effectively
      inhibited the growth of Gram-positive bacteria, pathogenic yeasts, and
      filamentous fungi, but it had only a weak effect on Gram-negative bacteria.
      Scanning electron micrograph analysis showed that the most characteristic change
      was swelling of the cells after exposure to the antibiotic. The antibiotic seems
      to alter the conformation of the microbial cell membrane, thereby changing its
      permeability, leading to osmotic shock.

PMID- 9627387
TI  - Effect of drying on bioremediation bacteria properties.
AB  - Bioremediation bacteria with drought-resistance characteristics were selected and
      compared to a collection of 10 strains selected only for their bioremediation
      properties. Twenty-six strains were selected from dried diesel-polluted soil, and
      they exhibit a better level of survival during drying, compared to collection
      bioremediation strains (two orders of magnitude difference). The lyophilization
      process does not affect the strains' ability to grow on xenobiotic compound when
      measured immediately after drying. However, collection bioremediation strains
      selected only for their bioremediation properties lose up to 80% of their
      properties when stored at 25 degrees C for 15 d, but the strains selected for
      their drought resistance lose their properties to a lesser extent during the same
      period. The maximal growth rate and the rate of xenobiotic degradation of the
      still-active cells are not affected by the drying process.

PMID- 9627388
TI  - Factors that affect the biosynthesis of xylitol by xylose-fermenting yeasts. A
      review.
AB  - Xylitol is a sweetener with important technological properties like
      anticariogenicity, low caloric value, and negative dissolution heat. Because it
      can be used successfully in food formulations and pharmaceutical industries, its
      production is in great demand. Xylitol can be obtained by microbiological
      process, since many yeasts and filamentous fungi synthesize the xylose reductase
      enzyme, which catalyses the xylose reduction into xylitol as the first step in
      the xylose metabolism. The xylitol production by biotechnological means has
      several economic advantages in comparison with the conventional process based on
      the chemical reduction of xylose. The efficiency and the productivity of this
      fermentation chiefly depends upon the microorganism and the process conditions
      employed. In this mini-review, the most significant upstream parameters on
      xylitol production by biotechnological process are described.

PMID- 9627389
TI  - Cloning and sequence analysis of the poly (3-hydroxyalkanoic acid)-synthesis
      genes of Pseudomonas acidophila.
AB  - Pseudomonas acidophila can grow with CO2 as a sole carbon source by the
      possession of a recombinant plasmid that clones genes that confer
      chemolithoautotrophic growth ability derived from the H2-oxidizing bacterium
      Alcaligenes hydrogenophilus. H2-oxidizing bacteria produce poly(3-hydroxybutyric
      acid) (PHB) from CO2, but recombinant P. acidophila can produce the more useful
      biopolymer poly(3-hydroxyalkanoic acid) (PHA). In this study, the pha genes of P.
      acidophila were cloned and a sequence analysis was carried out. A gene library
      was constructed using the cosmid vector pVK102. A recombinant cosmid carrying the
      pha genes was selected by the complementation of a PHB-negative mutant of
      Alcaligenes eutrophus H16. The resulting recombinant cosmid pIK7 contained a 14.8
      kb DNA insert. Subcloning was done. and the recombinant plasmid pEH74 was
      selected by hybridization with the A. eutrophus H16 pha genes. Escherichia coli
      possessing pEH74 produced PHB, indicating that pEH74 contained the pha genes of
      P. acidophila. The nucleotide sequences of the PHA-synthesis genes phaA (beta
      ketothiolase), phaB (acetoacetyl-CoA reductase), and phaC (PHA synthase) in pEH74
      were determined. The homologies of phaA, phaB, and phaC between P. acidophila and
      A. eutrophus H16 were 64.7, 76.1 and 56.6%, respectively.

PMID- 9627390
TI  - Thermal stability and energy of deactivation of free and immobilized
      amyloglucosidase in the saccharification of liquefied cassava starch.
AB  - Amyloglucosidase from Novo (Copenhagen, Denmark) was immobilized in controlled
      pore silica particles with the silane-glutaraldehyde covalent method. Thermal
      stability of the free and immobilized enzyme (IE) was determined with 30% (w/v)
      alpha-amylase liquefied cassava starch, pH 4.5, temperatures from 35 to 75
      degrees C. Free amyloglucosidase maintained its activity practically constant for
      240 min and temperatures up to 50 degree C. The IE has shown higher stability
      retaining its activity for the same period up to 60 degrees C. Half-life for free
      enzyme was 20.6, 6.44, 2.07, 0.69, and 0.24 h for 55, 60, 65, 70, and 75 degrees
      C, respectively, whereas the IE at the same temperatures had half-lives of 116.4,
      30.88, 8.52, 2.44, and 0.73 h. The energy of thermal deactivation was thus 50.6
      and 57.6 kcal/mol, respectively for the free and IE, confirming stabilization by
      immobilization.

PMID- 9627392
TI  - Ethanol production from AFEX-treated forages and agricultural residues.
AB  - Lignocellulosic materials derived from forages, namely timothy grass, alfalfa,
      reed canary grass, and agricultural residues, such as corn stalks and barley
      straw, were pretreated using ammonia fiber explosion (AFEX) process. The
      pretreated materials were directly saccharified by cellulolytic enzymes. Sixty to
      80% of theoretical yield of sugars were obtained from the pretreated biomasses.
      Subsequent ethanolic fermentation of the hydrolysates by Pachysolen tannophilus
      ATCC 32691 resulted in 40-60% of theoretical yield after 24 h, based on the
      sugars present in the hydrolysates. The uptake of sugars was not complete,
      indicating a possible inhibitory effect on P. tannophilus during the fermentation
      of these substrates.

PMID- 9627391
TI  - Hydrolysis of cellulose using ternary mixtures of purified cellulases.
AB  - The saccharification of microcrystalline cellulose by reconstituted ternary
      mixtures of purified cellulases (one endoglucanase and two cellobiohydrolases)
      has been studied over the entire range of mixture compositions. Ternary plots are
      used to compare the performance of five synthetic mixtures drawn from the
      cellulase systems of Acidothermus cellulolyticus, Trichoderma reesei,
      Thermomonospora fusca, and Thermotoga neapolitana. Results reveal that at least
      one synthetic mixture utilizing enzymes from three different organisms delivers
      performance competitive with that of a "native" (i.e., co-evolved) ternary system
      drawn exclusively from T. reesei. This heterologous system, consisting of the
      endoglucanase E1 from A. cellulolyticus and the exoglucanases CBHI from T. reesei
      and E3 from T. fusca, is forgiving from the system-design point of view, in that
      it delivers high saccharification rates over a wide range of mixture
      compositions.

PMID- 9627393
TI  - Nonisothermal simultaneous saccharification and fermentation for direct
      conversion of lignocellulosic biomass to ethanol.
AB  - The enzymatic reaction in the simultaneous saccharification and fermentation
      (SSF) is operated at a temperature much lower than its optimum level. This forces
      the enzyme activity to be far below its potential, consequently raising the
      enzyme requirement. To alleviate this problem, a nonisothermal simultaneous
      saccharification and fermentation process (NSSF) was investigated. The NSSF is
      devised so that saccharification and fermentation occur simultaneously, yet in
      two separate reactors that are maintained at different temperatures.
      Lignocellulosic biomass is retained inside a column reactor and hydrolyzed at the
      optimum temperature for the enzymatic reaction (50 degrees C). The effluent from
      the column reactor is recirculated through a fermenter, which runs at its optimum
      temperature (20-30 degrees C). The cellulase enzyme activity is increased by a
      factor of 2-3 when the hydrolysis temperature is raised from 30 to 50 degrees C.
      The NSSF process has improved the enzymatic reaction in the SSF to the extent
      that it reduces the overall enzyme requirement by 30-40%. The effect of
      temperature on beta-glucosidase activity was the most significant among the
      individual cellulase compounds. Both ethanol yield and productivity in the NSSF
      are substantially higher than those in the SSF at the enzyme loading of 5 IFPU/g
      glucan. With 10 IFPU/g glucan, improvement in productivity was more discernible
      for the NSSF. The terminal yield attainable in 4 d with the SSF was reachable in
      40 h with the NSSF.

PMID- 9627394
TI  - Batch foam recovery of sporamin from sweet potato.
AB  - The major sweet potato root protein, sporamin (which comprises about 80-90% of
      the total protein mass in the sweet potato) easily foams in a bubble/foam
      fractionation column using air as the carrier gas. Control of that foam
      fractionation process is readily achieved by adjusting two variables: bulk
      solution pH and gas superficial velocity. Varying these parameters has an
      important role in the recovery of sporamin in the foam. Changes in the pH of the
      bulk solution can control the partitioning of sporamin in the foam phase from
      that in the bulk phase. A change in pH will also affect the amount of foam
      generated. The pH varied between 2.0 and 10.0 and the air superficial velocities
      (V0) ranged between 1.5 and 4.3 cm/s. It was observed in these ranges that, as
      the pH increased, the total foamate volume decreased, but the foamate protein
      (mainly sporamin) concentration increased. On the other hand, the total foamate
      volume increased significantly as the air superficial velocity increased, but the
      foamate concentration decreased slightly. The minimum residual protein
      concentration occurred at pH 3.0 and V0 = 1.5 cm/s. On the other hand, the
      maximum protein mass recovery occurred at pH 3.0 and at V0 = 4.3 cm/s.

PMID- 9627395
TI  - Batch foam fractionation of kudzu (Pueraria lobata) vine retting solution.
AB  - The aqueous protein solution from kudzu (Pueraria lobata) vine retting broth,
      without the addition of other surfactants, was foam-fractionated in a vertical
      tubular column with multiple sampling ports. Time-varying trajectories of the
      total protein levels were determined to describe the protein behavior at six
      positions along the 1-m column. The lowest two trajectories of this batch process
      represented a loss of proteins from the bulk liquid and tended to merge and decay
      together in time; the other trajectories displayed a gain in proteins in the foam
      phase. These upper column port protein concentration trajectories generally
      increased in time up to 45 mm, followed by a decrease, reflecting the removal of
      proteins from the column ports. The foam became dryer as it passed up the column
      to the top port. The protein concentration was about 5-8x higher in the top port
      foam than in the initial bulk solution, mainly as a result of liquid drainage
      from the foam along the column axis. This concentration increase in the collected
      foam was dependent on the initial pH of the bulk solution. The mol-wt profile of
      the proteins in the concentrated foam effluent was determined by one-dimensional
      gel electrophoresis. An analysis of the gel electropherograms indicated that the
      most abundant proteins could be cellulases and pectinases.

PMID- 9627396
TI  - Biosorption of nickel using filamentous fungi.
AB  - Nickel (Ni) uptake capability from aqueous solutions was studied in a filamentous
      fungi strains group of Rhizopus sp., Penicillium sp. Aspergillus sp., Trichoderma
      sp., Byschoclamyss sp., and Mucor sp. The metal uptake of a Rhizopus sp. strain,
      which has the highest uptake capacity, was corroborated by electron microscopy;
      no Ni deposits were observed on the cell wall, but rather a homogeneous
      accumulation was seen on the cell surface. The influence on the capacity of metal
      uptake by environmental parameters such as pH, temperature, time, and the
      interference of other ions in the solution, was also studied. Nickel accumulation
      by the selected strains is fast, occurring in less than 30 min, and does not
      require a microorganism's active metabolism to take place. The sorption isotherms
      were established for the selected fungi, in order to determine the maximum metal
      uptake capacity. The sorption isotherms were fixed to the mathematical models of
      Freundlich and Langmuir, obtaining better performance on the Langmuir model.

PMID- 9627397
TI  - Recovery and refining of Au by gold-cyanide ion biosorption using animal fibrous
      proteins.
AB  - Animal fibrous proteins (AFPs) such as egg-shell membrane (ESM), chicken feather
      (CF), wool, silk, or elastin are an intricate network of stable and water
      insoluble fibers with high surface area and are abundant bioresources. Every AFP
      tested was found to accumulate gold-cyanide ion from aqueous solutions in high
      yield, depending on pH and some other parameters. Gold-cyanide ion is adsorbed by
      AFP at low pH range, with maximum binding observed at approx pH 2.0. Under the
      certain conditions, gold-cyanide ion was accumulated up to 8.6, 7.1, 9.8, 2.4,
      and 3.9% of dry weight on ESM, CF, wool, silk, and elastin, respectively. In the
      case of ESM, it was found that ESM removed gold-cyanide ion almost quantitatively
      and almost all the gold uptake by ESM was easily desorbed with 0.1 M NaOH. ESM
      can be used repeatedly for the process of gold adsorption-desorption. The gold
      biosorptive capacity of ESM that was chemically modified with glutaraldehyde was
      higher than that of control. In column procedure, ESM packed on column removed
      gold-cyanide ion from the dilute aqueous solution to extremely low concentrations
      (nondetectable concentration of below 1 ppb).

PMID- 9627399
TI  - beta-Cyclodextrin production by simultaneous fermentation and cyclization.
AB  - Production of beta-cyclodextrin (CD) with high-dextrose equivalent (DE) starch
      hydrolysates by simultaneous fermentation and cyclization (SFC) gives higher
      yields than using only the enzyme CGTase, because fermentation eliminates glucose
      and maltose that inhibit CD production, while at the same time, produces ethanol
      that increases yield. A 10% (w/v) solution of cassava starch, liquefied with
      alpha-amylase, was incubated with CGTase using: only the enzyme, added ethanol
      (from 1 to 5%), and added yeast S. cerevisiae (12% w/v), plus nutrients, the
      latter being the SFC process. Reaction conditions were: 38 degrees C, pH 6.0, DE
      from 2 to 25, and 3.3 mL of CGTase/L. The yield of beta-CD has decreased with an
      increase in DE, and maximum reaction yields were found for DE equal to 3.54,
      reaching 5.6, 14.7, and 11.5 mM beta-CD, respectively. For an increase of DE, of
      approx 6 times (from 3.54 to 23.79), beta-CD yield decreased 6 times for the
      first, and second reaction media with 3% (v/v) ethanol, and only approx 3 times
      for SFC (from 11.5 to 3.73 mM), showing that this process is less sensitive to
      variations in the DE.

PMID- 9627400
TI  - Production of L-malic acid via biocatalysis employing wild-type and respiratory
      deficient yeasts.
AB  - The yeast Saccharomyces cerevisiae has been used to efficiently produce L-malic
      acid from fumaric acid. Fumarase is responsible for the reversible conversion of
      fumaric and L-malic acids in the TCA cycle. To investigate the function of
      mitochondrial and cytoplasmic fumarase isoenzymes in L-malic acid bioconversion,
      a wild-type strain and a cytoplasmic respiratory-deficient mutant devoid of
      functional mitochondria were employed. The mutant strain, which only contained
      the cytoplasmic fumarase, was still functional in fumaric acid to L-malic acid
      bioconversion However, its specific conversion rate was much lower (0.20 g/g.h)
      than that of the wild-type strain (0.55 g/g.h).

PMID- 9627401
TI  - Biotechnological production of xylitol from agroindustrial residues. Evaluation
      of bioprocesses.
AB  - Batch, fed-batch, and semicontinuous fermentation processes were used for the
      production of xylitol from sugarcane bagasse hemicellulosic hydrolysate. The best
      results were achieved by the semicontinuous fermentation process: a xylitol yield
      of 0.79 g/g with an efficiency of 86% and a volumetric productivity of 0.66
      g/L/h.

PMID- 9627402
TI  - In situ mutagenesis and chemotactic selection of microorganisms in a diffusion
      gradient chamber.
AB  - A new method has been developed to rapidly generate and select microbial strains
      having increased resistance to an inhibitory compound. The method combines in
      situ mutagenesis with use of a continuous gradient of the inhibitor to sort cells
      according to their resistance levels. Microbial chemotaxis is induced to
      accelerate the selection process. The method was used to develop a strain of E.
      coli having a feedback-resistant DAHP synthase enzyme. An unsteady-state
      mathematical model of the process has been developed. The model, that can
      reproduce key trends observed experimentally, was used to explore the effects of
      chemotaxis on the efficiency of the selection process.

PMID- 9627403
TI  - Bioconversion of fumaric acid to succinic acid by recombinant E. coli.
AB  - Succinic acid was produced efficiently from fumaric acid by a recombinant E. coli
      strain DH5 alpha/pGC1002 containing multicopy fumarate reductase genes. The
      effects of initial fumaric acid and glucose concentration on the production of
      succinic acid were investigated. Succinic acid reached 41 to over 60 g/L in 48.5
      h starting with 50 to 64 g/L fumaric acid. Significant substrate inhibition was
      observed at initial fumaric acid concentration of 90 g/L. L-Malic acid became the
      major fermentation product under these conditions. Provision of glucose (5-30
      g/L) to the fermentation medium stimulated the initial succinic acid production
      rate over two folds.

PMID- 9627404
TI  - Accumulation of biodegradable copolyesters of 3-hydroxy-butyrate and 3
      hydroxyvalerate in Alcaligenes eutrophus.
AB  - Biodegradable copolyesters of 3-hydroxybutyrate-co-3-hydroxyvalerate (3HB-3HV)
      were produced by Alcaligenes eutrophus in a two-staged process, namely growth
      stage and nitrogen-deficient polyester-accumulation stage. When C5 was used as
      the sole carbon source, the copolyester contained 43 mol % of 3HV. A range of
      copolyesters with 0-43 mol % of 3HV could be produced by using a medium
      containing different concentration ratios of butyric acid C4 and C5. Tm of PHB
      homopolymer was 177.6 degrees C and that of copolyester with highest 3HV mol
      fraction of 43% was 99.0 degrees C. C5 concentration in the medium could be an
      effective means to control the polymeric composition and mechanical properties of
      the copolyesters accumulated in A. eutrophus.

PMID- 9627405
TI  - Efficient production of mannan-degrading enzymes by the basidiomycete Sclerotium
      rolfsii.
AB  - Sclerotium rolfsii CBS 191.62 was cultivated on a number of carbon (C) sources,
      including mono- and disaccharides, as well as on polysaccharides, to study the
      formation of different mannan-degrading enzyme activities. Highest levels of
      mannanase activity were obtained when alpha-cellulose-based media were used for
      growth, but formation of mannanase could not be enhanced by employing
      galactomannan as the only carbon source. Although both xylanase and cellulase
      formation was almost completely repressed when S. rolfsii was grown on more
      readily metabolizable carbohydrates, including glucose or mannose, considerable
      amounts of mannanase activity were secreted under these growth conditions.
      Enhanced mannanase production only commenced when glucose was depleted in the
      medium. The maximal mannanase activity of 240 IU/mL obtained in a laboratory
      fermentation is remarkable. Mannanase activity formed under these derepressed
      conditions could be mainly attributed to one major, acidic mannanase isoenzyme
      with a pI value of 2.75.

PMID- 9627406
TI  - Rapid purification and molecular modeling of AaIT peptides from venom of
      Androctonus australis.
AB  - As recombinant viruses expressing scorpion toxins are moving closer toward the
      market, it is important to obtain large amounts of pure toxin for biochemical
      characterization and the evaluation of biological activity in nontarget
      organisms. In the past, we purified a large amount of Androctonus australis anti
      insect toxin (AaIT) present in the venom of A. australis with an analytical
      reversed-phase column by repeated runs of crude sample. We now report 20 times
      improved efficiency and speed of the purification by employing a preparative
      reversed-phase column. In just two consecutive HPLC steps, almost 1 mg of AaIT
      was obtained from 70 mg crude venom. Furthermore, additional AaIT was obtained
      from side fractions in a second HPLC run. Recently discovered insect selective
      toxin, AaIT5, was isolated simultaneously from the same venom batch. It shows
      different biological toxicity symptoms than the known excitatory and depressant
      insect toxins. AaIT5 gave 100% mortality with a dose of less than 1.3 micrograms
      against fourth-instar tobacco budworms Heliothis virescens 24 h after injection.
      During the purification process, we implemented mass spectrometry in addition to
      bioassays to monitor the presence of AaIT and AaIT5 in the HPLC fractions. Mass
      spectrometric screening can unambiguously follow the purification process and can
      greatly facilitate and expedite the downstream purification of AaIT and AaIT5
      eliminating the number of bioassays required. Further, electrospray ionization
      was compared with matrix-assisted desorption/ionization and evaluated as a method
      of choice for mass spectrometric characterization of fractions from the venom
      purification for it provided higher mass accuracy and relative quantitation
      capability. Molecular models were built for AaIT5, excitatory toxin AaIT4, and
      depressant toxin LqhIT2. Three-dimensional structure of AaIT5 was compared with
      structures of the other two toxins, suggesting that AaIT5 is similar to
      depressant toxins.

PMID- 9627407
TI  - Drosophila acetylcholinesterase: effect of post-translational [correction of post
      traductional] modifications on the production in the baculovirus system and
      substrate metabolization.
AB  - Acetylcholinesterase cDNAs from Drosophila melanogaster modified on its primary
      sequence were cloned into baculovirus and were expressed in Sf9 cells with the
      aim to identify a mutant form that produces the enzyme at a high level. Directed
      mutagenesis was used in order to independently knockout different sites of post
      translational modifications: exchange of the C-terminal hydrophobic peptide for a
      glycolipid molecule, dimerization by disulfide bridge, N-linked glycosylation at
      the five accessible sites, and subunit formation by proteolytic cleavage of a
      hydrophilic peptide found in the precursor. Another mutation involved the
      elimination of a free cysteine in the mature protein. All mutations involving
      post-translational modifications resulted in lower recoveries, suggesting that
      they are useful for maintaining high amounts of protein in the synapse. By
      contrast, elimination of a free cysteine in the mature protein permitted an
      increase in the level of production of the enzyme. These mutations did not affect
      specific activity of the enzyme at substrate concentrations ranging from 3 microM
      to 200 mM, suggesting that activation and inhibition of the enzyme activity does
      not originate from a polymorphism in post-translational modifications.

PMID- 9627408
TI  - Mating in Heliothis virescens: transfer of juvenile hormone during copulation by
      male to female and stimulation of biosynthesis of endogenous juvenile hormone.
AB  - Studies were undertaken to determine whether adult males of Heliothis virescens
      transfer juvenile hormone (JH) to females during copulation, and an in vitro
      radiochemical assay was used to determine whether mating causes an allatotropic
      effect, i.e., stimulation of JH biosynthesis by corpora allata (CA). In vitro, CA
      from 3-day-old mated females synthesized and released approximately 2.5 times
      total JH as that of CA from comparably aged virgin females. Of the homologues, JH
      II exhibited significant increase in mated females; JH I also increased but not
      significantly. JH III remained similar to that of virgin females. This is the
      first demonstration of an allatotropic effect of mating in moths. In contrast to
      the female, CA of virgin males did not produce any JH, but accessory sex glands
      (ASG) in 3-day-old males synthesized small amounts of JH. Immediately after adult
      emergence, male ASG contained approximately 1.5 ng JH I and II, which increased
      by 12 h after emergence and remained at this high level up to 54 h after
      emergence. JH III was barely detected in ASG. JH in ASG of mated male immediately
      after uncoupling was depleted almost completely, and 24 h later recovered to
      levels comparable to that of 54-h-old virgin male. Virgin female bursa copulatrix
      did not contain any JH, but mated female bursa, immediately after uncoupling, had
      JH at levels comparable to that observed in virgin male ASG. By 6 h after
      uncoupling, JH levels decreased dramatically in mated female bursa. These data
      suggest the transfer of JH to females by the male.

PMID- 9627409
TI  - Stimulus-driven attentional capture is contingent on attentional set for
      displaywide visual features.
AB  - This research showed that the current criterion for stimulus-driven attentional
      capture is not sufficient to rule out goal-directed processes that are critical
      for producing attentional capture. This was shown by demonstrating a contingency
      between displaywide visual features (i.e., features that signal the appearance of
      the task-relevant target display as a whole) and the features that capture
      attention. In Experiment 1, the target display was signaled by both color and
      onset; in Experiment 2, the target display was signaled only by onset. As
      expected, Experiment 1 showed that task-irrelevant color and onset distractors
      both captured attention, whereas Experiment 2 showed that only onset distractors
      captured attention. These contingencies suggest that the strongest evidence
      currently available for stimulus-driven attentional capture may be caused by goal
      directed processes.

PMID- 9627410
TI  - Representation of orientation and spatial frequency in perception and memory: a
      choice reaction-time analysis.
AB  - Discrimination and short-term memory for the orientation of sinusoidal gratings
      that differed in spatial frequency, and for the spatial frequency of gratings
      that differed in orientation, were measured in a same-different task with 0-10 s
      interstimulus intervals (ISI) between test and reference stimuli. Introducing a
      difference between test and reference stimuli on a second dimension, or
      increasing ISI, did not impair spatial discrimination in terms of accuracy, but
      choice reaction times for correct decisions were prolonged by both manipulations.
      Results suggest that perceptual discrimination is based on representations in
      which orientation and spatial frequency are conjointly coded and that decisions
      are reached by a serial process scanning multiple-tuned, labeled channels; short
      term memory may involve reactivation of these channels.

PMID- 9627411
TI  - Effects of spatial separation in visual pattern matching: evidence on the role of
      mental translation.
AB  - Effects of the spatial separation between 2 simultaneously presented random
      patterns on the ability to determine whether the patterns are identical up to a
      translational displacement across the retina were investigated by using signal
      detection methods. The patterns to be compared were presented on the periphery of
      an imaginary circle centered on fixation. Exposures were brief and postmasked. In
      Experiments 1 and 2, sensitivity (d') varied with exposure duration but not with
      the spatial separation between the patterns. In Experiment 3, the task was
      changed so that members of a "same" pair could differ by both a translation and a
      rotation. When the rotational component was O, d' was a monotonic decreasing
      function of the spatial separation between the stimuli. Apparently, in the
      special case, performance was based on mental alignment by a process of gradual
      mental translation of one of the members of a stimulus pair to the location of
      the other one.

PMID- 9627412
TI  - The role of attention in priming for left-right reflections of object images:
      evidence for a dual representation of object shape.
AB  - Three experiments investigated the role of visual attention in priming for object
      images and their left-right reflections. Objects to which participants attended
      were visually primed in both the same view and in the left-right reflected view;
      ignored objects were primed only in the same view. The effects of attention
      (attended vs. ignored) and view (same vs. reflected) were strictly additive.
      These results suggest that 2 separate representations mediate human object
      recognition (J.E. Hummel & B.J. Stankiewicz, 1996): One requires attention but is
      invariant with left-right reflection, whereas the other can be activated
      automatically but is sensitive to left-right reflection. Both representations
      appear to be invariant with translation across the visual field.

PMID- 9627413
TI  - Effect of same- and different-modality spatial cues on auditory and visual target
      identification.
AB  - A target identification paradigm was used to study cross-modal spatial cuing
      effects on auditory and visual target identification. Each trial consisted of an
      auditory or visual spatial cue followed by an auditory or visual target. The cue
      and target could be either of the same modality (within-modality conditions) or
      of different modalities (between-modalities conditions). In 3 experiments, a
      larger cue validity effect was apparent on within-modality trials than on between
      modalities trials. In addition, the likelihood of identifying a significant cross
      modal cuing effect was observed to depend on the predictability of the cue-target
      relation. These effects are interpreted as evidence (a) of separate auditory and
      visual spatial attention mechanisms and (b) that target identification may be
      influenced by spatial cues of another modality but that this effect is primarily
      dependent on the engagement of endogenous attentional mechanisms.

PMID- 9627414
TI  - Language discrimination by newborns: toward an understanding of the role of
      rhythm.
AB  - Three experiments investigated the ability of French newborns to discriminate
      between sets of sentences in different foreign languages. The sentences were low
      pass filtered to reduce segmental information while sparing prosodic information.
      Infants discriminated between stress-timed English and mora-timed Japanese
      (Experiment 1) but failed to discriminate between stress-timed English and stress
      timed Dutch (Experiment 2). In Experiment 3, infants heard different combinations
      of sentences from English, Dutch, Spanish, and Italian. Discrimination was
      observed only when English and Dutch sentences were contrasted with Spanish and
      Italian sentences. These results suggest that newborns use prosodic and, more
      specifically, rhythmic information to classify utterances into broad language
      classes defined according to global rhythmic properties. Implications of this for
      the acquisition of the rhythmic properties of the native language are discussed.

PMID- 9627415
TI  - The effects of neighborhood frequency in reading and lexical decision.
AB  - To test the effect of the frequency of orthographic "neighbors" on the
      identification of a printed word, two sets of words were constructed (equated on
      the number of neighbors, word frequency, and number of letters); in one set, the
      words had no higher frequency neighbors and in the other set, they had at least
      one higher frequency neighbor. Identification was slower for the latter set. In
      Experiment 1, this was indexed by longer response times in a lexical decision
      task. In Experiment 2, the target words were embedded in sentences, and slower
      identification was indexed by disruptions in reading: more regressions back to
      the words with higher frequency neighbors and longer fixations on the text
      immediately following these words. The latter results indicate that a higher
      frequency neighbor affects relatively late stages of lexical access, an
      interpretation consistent with both activation-verification and interactive
      activation models.

PMID- 9627416
TI  - Rehearsal in spatial working memory.
AB  - This article reports 3 experiments that tested a hypothesis regarding the nature
      of rehearsal in spatial working memory, one in which discrete shifts of spatial
      selective attention mediate the maintenance of location-specific representations.
      Experiment 1 demonstrated increases in visual processing efficiency for locations
      held in working memory, which suggested that attention was oriented toward these
      locations. Experiment 2 eliminated key alternative explanations for Experiment 1
      by using an identical stimulus display with a nonspatial memory task, and little
      or no facilitation of processing at memorized locations was found under these
      conditions. Finally, Experiment 3 showed that spatial working memory was impaired
      when participants were hindered in their ability to attend to memorized
      locations. It is argued that these results implicate selective spatial attention
      as a rehearsal mechanism for spatial working memory.

PMID- 9627417
TI  - Variations on a theme by chopin: relations between perception and production of
      timing in music.
AB  - A note interonset interval (IOI) increment in mechanically timed music is more
      difficult to detect where expressive lengthening typically occurs in artistic
      performance. Experiment 1 showed this in an excerpt from a Chopin etude and
      extended the task to IOI decrement detection. A simple measure of variation in
      perceptual bias was derived that correlated highly with the average timing
      pattern of pianists' performances, more so than with acoustic surface properties
      of the music. Similar results, but decreasing correlations, were obtained in each
      of four subsequent experiments in which the music was simplified in stages.
      Although local psychoacoustic effects on time perception cannot be ruled out
      completely, the results suggest that musical structure (melodic-rhythmic grouping
      in particular) has temporal implications that are reflected not only in
      musicians' motor behavior but also in listeners' time-keeping abilities.

PMID- 9627418
TI  - Adaptive internal model of intrinsic kinematics involved in learning an aiming
      task.
AB  - The elbow-joint angle and the shoulder-joint angle of participants aiming at
      targets were multiplied in an experiment that used a position-recording system
      and a cathode-ray tube screen. The linear transformation in joint angles
      (intrinsic coordinates) corresponded to a nonlinear transformation between the
      hand coordinates and the screen coordinates (extrinsic coordinates). We examined
      whether participants could learn this transformation in the intrinsic coordinates
      or in the extrinsic coordinates by investigating intermanual (between-hands)
      transfer under an intrinsically consistent condition and an extrinsically
      consistent condition. Positive intermanual transfer was observed in the former
      condition but not in the latter condition. Results suggest that participants can
      learn the linear transformation in joint angles under the intrinsic coordinates
      and that the central nervous system adaptively represents the intrinsic
      kinematics.

PMID- 9627419
TI  - On the relations between seen objects and components of potential actions.
AB  - Accounts of visually directed actions usually assume that their planning begins
      with an intention to act. This article describes three experiments that
      challenged this view through the use of a stimulus-response compatibility
      paradigm with photographs of common graspable objects as stimuli. Participants
      had to decide as fast as possible whether each object was upright or inverted.
      Experiments 1 and 2 examined the effect of the irrelevant dimension of left-right
      object orientation on bimanual and unimanual keypress responses. Experiment 3
      examined wrist rotation responses to objects requiring either clockwise or
      anticlockwise wrist rotations when grasped. The results (a) are consistent with
      the view that seen objects automatically potentiate components of the actions
      they afford, (b) show that compatibility effects of an irrelevant stimulus
      dimension can be obtained across a wide variety of naturally occurring stimuli,
      and (c) support the view that intentions to act operate on already existing motor
      representations of the possible actions in a visual scene.

PMID- 9627420
TI  - Selectivity in distraction by irrelevant featural singletons: evidence for two
      forms of attentional capture.
AB  - Four experiments addressed the degree of top-down control over attentional
      capture in visual search for featural singletons. In a modified spatial cuing
      paradigm, the spatial relationship and featural similarity of target and
      distractor singletons were systematically varied. Contrary to previous studies,
      all 4 experiments showed that when searching for a singleton target, an
      irrelevant featural singleton captures spatial attention only when defined by the
      same feature value as the target. Experiments 2, 3 and 4 provided a potential
      explanation for the discrepancy with previous studies by showing that irrelevant
      singletons can produce distraction effects that are dissociable from shifts of
      spatial attention. The results suggest the existence of 2 distinct forms of
      attentional capture.

PMID- 9627421
TI  - A common mechanism for illusory and occluded object completion.
AB  - New phenomena and results are reported that implicate a common contour
      interpolation mechanism in illusory and occluded (modal and amodal) object
      completion. In 3 experiments, a speeded classification task was used to study
      novel quasimodal displays in which occluded and illusory contours join. Results
      showed the same advantages in speed and accuracy over control displays for
      quasimodal, illusory, and occluded displays. The implications of quasimodal
      displays, along with another new display type in which contour linkages must
      precede determination of modal or amodal appearance, are considered. These
      logical considerations and empirical results suggest that amodal and modal
      completion depend on a common underlying mechanism that connects edges across
      gaps.

PMID- 9627422
TI  - Effects of age on performance in a finger-precuing task.
AB  - This study investigated age-related precuing effects in the finger-precuing task
      (J. Miller, 1982). In this task, a spatial precue provides partial advance
      information about which fingers to use for responding. Results indicated a
      substantial age-related deficit in preparing 2 fingers on 2 hands, but not on 1
      hand. This disparate set of findings does not provide strong support for A. A.
      Hartley's (1993) hypothesis that anterior brain attention systems responsible for
      selection-for-action are compromised with advancing age. Finally, the authors
      report that advancing age increasingly slows reaction time more to the inner than
      to the outer stimulus-response positions. A possible mechanism of this age
      related bowed stimulus-response position effect is discussed.

PMID- 9627423
TI  - A comparison of intra- and interpersonal interlimb coordination: coordination
      breakdowns and coupling strength.
AB  - Intra- and interpersonal interlimb coordination of pendulums swung from the wrist
      was investigated. For both kinds of coordination, the steady state and breakdown
      of bimanual rhythmic coordination as indexed by the time series of the relative
      phase angle phi were studied under the manipulation of coordination mode,
      frequency of oscillation, and the difference in the eigenfrequencies (preferred
      tempos) of the individual oscillating limbs. The properties observed for both
      intra- and interpersonal coordination were those predicted by a dynamical model
      of rhythmic coordination that considers the coordinated limbs coupled to be
      nonlinear oscillators. Using a regression method, the coupling strengths of the
      coupled system were recovered. As predicted by the dynamical model, the strength
      of the dynamic was generally greater for the in-phase than the anti-phase mode
      and decreased with increasing frequency. Further, the strength of the
      interpersonal interlimb coupling was weaker than that of intrapersonal interlimb
      coupling.

PMID- 9627424
TI  - Cognitive motion extrapolation and cognitive clocking in prediction motion task.
AB  - An interruption paradigm was used to measure judgments that rely on cognitive
      extrapolation of approach and lateral motion. In some conditions the pattern of
      errors was consistent with that obtained with time-to-contact (TTC) judgments
      measured with a prediction motion (PM) task. Also, the slope of the relationship
      between estimated and actual TTC in judgments of approaching objects decreased
      when visual information about the environment between the observer and the
      display was minimized. Moreover, the accuracy of relative duration judgments of
      visual (but not auditory) stimuli decreased when a PM task was performed
      concurrently. Results are consistent with the notion that PM tasks involve
      cognitive motion extrapolation rather than solely a clocking process that counts
      down TTC.

PMID- 9627425
TI  - Effects of stimulus duration and intensity on simple reaction time and response
      force.
AB  - Previous research indicates that response force increases with stimulus intensity
      in simple reaction time (SRT) tasks. This result contradicts the common view that
      the perceptual system activates the motor system via a punctate go signal of
      fixed size. An elaborated view assumes that the size of the go signal depends on
      stimulus intensity so that more intense stimuli yield more forceful responses. In
      order to examine the latter hypothesis, the present experiments manipulated
      stimulus duration as well as intensity. Response force increased with duration
      even beyond a critical value of about 60 ms at which stimulus duration no longer
      affected SRT. In addition, increasing the duration of a stimulus also increased
      the duration of force output. These findings argue against models with punctate
      transmission of activation to the motor system. Certain continuous models and
      variable output models with prolonged go signals provide acceptable accounts of
      these effects.

PMID- 9627426
TI  - Probing the locus of confidence judgments: experiments on the time to determine
      confidence.
AB  - Three experiments investigated the properties of the time to determine confidence
      to determine the processing locus for the judgment of confidence. Results suggest
      that when the primary decision is made under speed stress, confidence is
      determined postdecisionally and involves a memory-based, computational algorithm.
      This strategy frees the primary decision of processing time and permits the
      accurate diagnosis of decision errors. When the primary decision is made under
      accuracy stress, however, the determination of confidence is initiated, or can
      even be completed, during the primary decision process. This strategy permits
      confidence to be used in the adaptive regulation of the decisional parameters
      during the decision process but yields poorer diagnosticity of errors when they
      occur. The latter finding also implies that primary decision latencies include
      time to determine confidence, rendering such data difficult, if not impossible,
      to model empirically. Implications for contemporary decision models that provide
      a basis for confidence in human judgment are discussed.

PMID- 9627427
TI  - Visual marking of moving objects: a role for top-down feature-based inhibition in
      selection.
AB  - Recently, the authors presented evidence that new items can be prioritized for
      selection by the top-down attentional inhibition of old stimuli already in the
      field (visual marking; D. G. Watson & G. W. Humphreys, 1997). In this article the
      authors assess whether this inhibition extends to moving old items and test an
      alternative account of visual marking. Six experiments showed that old moving
      items could be inhibited provided they did not undergo abrupt property changes.
      Further, and in contrast to effects with static stimuli, the marking of old
      moving stimuli was based on inhibition applied at the level of a whole feature
      map, rather than at their locations. The results also rule out an alternative
      account of visual marking based on the top-down weighting of dynamic or static
      processing pathways.

PMID- 9627428
TI  - How is body orientation controlled during somersaulting?
AB  - How body orientation is controlled during somersaulting was investigated in 2
      experiments that analyzed the kinematics of 223 backward standing somersaults. In
      Experiment 1, open-loop, initial-condition (flight duration), and prospective
      (time to contact, or TC1) control strategies were tested as candidates for the
      regulation of body moment of inertia during the jump. Decreasing between-trials
      variability of body orientation over time as well as a negative correlation
      between body angular velocity and TC1 suggested that the moment of inertia was
      regulated prospectively. In Experiment 2, the visual basis for this regulation
      was examined by asking experts and novices to execute somersaults either with
      eyes closed or open. Results showed that the prospective regulation observed in
      the vision condition disappeared in the no-vision condition with the experts,
      arguing in favor of a visual control during the jump. Such a coupling was absent
      with the novices, thus illustrating the role played by the perception-action
      cycle in the learning process.

PMID- 9627429
TI  - Where have all the nurses gone?

PMID- 9627430
TI  - Stepping as an exercise modality for improving fitness and function.
AB  - This article describes three stepping modes, summarizes research on stepping in
      healthy adults and patients with peripheral vascular disease, and discusses
      clinical implications and directions for future research. Stepping exercise has
      been shown to increase cardiorespiratory fitness in healthy adults and increase
      physical function in patients with peripheral vascular disease. Although further
      research is warranted, stepping exercise has potential value as a nursing
      intervention to correct alterations in physical mobility in selected populations.
      Stepping is proposed as an alternative exercise strategy; one which adds variety
      to exercise routines and may enhance long-term exercise adherence.

PMID- 9627431
TI  - Effect of comprehensive care on pregnancy outcomes.
AB  - The purpose of the study was to compare pregnancy outcomes of low socioeconomic
      pregnant women receiving prenatal care at a prototype, comprehensive,
      multidisciplinary tertiary clinic with outcomes of a matched sample who received
      prenatal care from a variety of area public health clinics. Multidisciplinary
      clinic subjects were matched by age, race, and parity to 175 control subjects
      selected from labor and delivery logs of the general hospital that services the
      entire community. There were significant differences between groups on the
      measures of gestational age (t[174] = 2.50, p < .01), maternal risk factors
      (t[174] = 11.12, p < .0), and infant complications (t[174] = 5.86, p < .01).
      Infant birthweight and APGAR scores were not significantly different between the
      multidisciplinary clinic subjects and the matched sample. This study showed the
      importance of comprehensive prenatal care for low socioeconomic women at high
      risk for obstetrical and medical complications.

PMID- 9627432
TI  - The process of infant pain assessment.
AB  - This study describes the process pediatric nurses used to assess pain in 0- to 12
      month-old infants. Qualitative analyses of open-ended interviews with 40
      pediatric nurses with from 1 to 20 years of experience produced an infant pain
      assessment model. This model explicates a "principle of consolability" and
      describes how nurses apply this principle, using comfort measures, in assessing
      pain of preverbal infants. Because this model makes processes involved in infant
      pain assessment explicit, it can be useful in teaching nursing students or novice
      pediatric nurses and in formulating hypotheses for further study.

PMID- 9627433
TI  - Triggers of overeating and related intervention strategies for women who weight
      cycle.
AB  - The purpose of this study was to describe overeating episodes of overweight women
      who weight cycle compared with women of normal weight. Repeated overeating can be
      a major source of excess calories that may lead to weight gain in women who have
      weight cycled. Interview transcripts about overeating episodes of 45 women were
      subjected to a content analysis in a qualitative secondary analysis of data. Four
      patterns emerged from the data: planned overeating, power/control, relationships
      with others, and unpleasant feelings. Three intervention strategies are described
      to assist women who have weight cycled to understand and deal with feelings that
      trigger overeating, including strategies to stop overeating, feel their feelings,
      and fight fairly.

PMID- 9627434
TI  - Behaviors in type II diabetes during contingency contracting.
AB  - The purpose of this study was to use existing data to describe the behaviors
      performed by 117 subjects with Type II diabetes who wrote contingency contracts
      with nurses. Data were analyzed from a larger, randomized clinical trial of
      contingency contracting to improve clinical outcomes. Subjects had a high rate of
      completion of behaviors in contingency contracts (M = 90.9%). Subjects performed
      a median of six behaviors overall and up to a median of three behaviors of each
      of the diabetic regimen behaviors. The majority performed diet (n = 68, 58.1%)
      and exercise (n = 69, 58.9%) behaviors, with only one third performing both
      behaviors (n = 40, 34.2%). The most frequent behavioral strategies used were
      breaking the behavior into steps and self-monitoring the behavior. The
      contingency contracting intervention should be modified to be more comprehensive
      with increased recognition of the time and effort required for concurrently
      changing diet and exercise.

PMID- 9627435
TI  - The Faces Pain Scale: reliability and validity with mature adults.

PMID- 9627436
TI  - Research peer review: a committee when none is required.
AB  - Good research does not occur in isolation. The researcher should choose one or
      more reviewers to serve as quality monitors of the process. The reviewer(s)
      should be carefully chosen, and the relationship should be nurtured. When the
      research is not enhanced by the relationship, new reviewers should be sought even
      if this delays the research process. A good study has enough glory to share with
      all reviewers, and a poor study is a heavy burden to bear alone.

PMID- 9627437
TI  - Administrative issues in the measurement and management of outcomes.

PMID- 9627438
TI  - [Liver transplantation in a child from living parents as donors].
AB  - The shortage of cadaveric liver grafts is very detrimental for young children
      because of the scarcity of small size-matched pediatric donors. Living related
      liver transplantation combined with innovative techniques using a partial
      cadaveric liver graft (reduced liver, split liver) gives excellent results and
      has a positive impact on the overall management of children needing a liver
      transplant.

PMID- 9627439
TI  - [Positron emission tomography using 18F-fluorodeoxyglucose in oncology].
AB  - The use of 18FDG highlights biochemical disturbations present in cancerous
      tissues, in particular the accelerated glycolysis related to increased glucose
      transporters and to the increased activity of the enzymes of glycolysis. The
      recent availability of whole-body PET tomographs has opened the way to a variety
      of oncological applications. The usefulness of 18FDG-PET at various stages of
      diagnosis, staging and therapy follow-up has now been demonstrated. We
      demonstrate some of these indications, in particular in lung cancers, lymphomas
      and colorectal carcinomas.

PMID- 9627440
TI  - [Supportive care in oncology].
AB  - At the present time, cancer can be cured in about 50% of the patients, mainly
      through surgical procedures associated or not with radiotherapy and/or
      chemotherapy. For the rest of these patients, therapy will only be palliative; in
      other words, these patients will not be cured but radiation therapy and/or
      chemotherapy will control the symptoms of the neoplastic disease and improve the
      survival in a substantial proportion of them. In those patients, it is essential
      to weight the benefits and the risks of such palliative therapies in order to
      maintain an optimal quality of life. Supportive care is aiming at the control of
      all the manifestations associated with specific treatment of cancer. The nature
      of supportive care changes as the neoplastic disease progresses; eventually, it
      will consist only of measures providing optimal comfort to the patients.

PMID- 9627441
TI  - [Antioxidant micronutrients and chronic degenerative pathology: the role of
      complementary nutritional doses].
AB  - Many epidemiologic studies based on an observational approach indicate that a
      high dietary intake or high blood concentrations of some antioxidant
      micronutrients are associated with a reduced risk of cardiovascular diseases and
      cancer at several common sites. Inconsistent results of intervention trials
      suggest that low risk of pathologies may be related to multiple nutrients
      consumed, at nutritional doses, and in combination. This hypothesis was the
      rationale of the SU.VI.MAX. study, a randomized double-blind, placebo-controlled,
      primary-prevention trial designed to test the efficacy of a daily supplementation
      with antioxidant vitamins and minerals at nutritional doses in reducing the major
      health problems in industrialized countries, and especially the main causes of
      premature death (cancers and cardiovascular diseases).

PMID- 9627442
TI  - [Recommendation of the introduction of salt fluoridation for caries prevention in
      Hungary].
AB  - The aim of the paper is to review the four decades' long history of salt
      fluoridation, and to report on experiments and activities in Hungary in the
      course of the last three decades, aiming the country-wide introduction of
      domestic salt fluoridation. Salt fluoridation, as a caries preventive method was
      first introduced in Switzerland, in 1955, later caries-reducing effects were
      studied in Columbia, Spain and Hungary. The results of the clinical experiments
      of K. Toth performed in Szeged, Hungary, showed after 17 years a caries reduction
      of about 66%. These results contributed significantly to the introduction of salt
      fluoridation in several (France, Costa Rica, Jamaica, Germany) countries. Leaders
      of Hungarian dentistry tried to introduce salt fluoridation since 1972, but due
      to the antifluoride lobby, and organisational difficulties, the authorization was
      delayed. However, in the last three years in the course of several discussions
      and debates within the top-commissions, a positive statement was issued recently
      by the Hungarian Academy of Sciences on the support for the country-wide
      introduction of domestic salt fluoridation at earliest possible convenience.

PMID- 9627443
TI  - [Taking position on the introduction of fluoridation for the prevention of dental
      caries].

PMID- 9627444
TI  - [Orthodontic principles in the management of congenital absence of tooth roots in
      permanent teeth].

PMID- 9627445
TI  - [Odontogenic necrotizing fasciitis of the neck].
AB  - A case of a patient, who has recovered from odontogen necrotising fascitis of the
      neck, is described. The pathophysiological and bacterial aspects are summarised.
      The following are important: definite and early surgical intervention, uncovered
      wound treatment, combined antibiotic therapy because of the aerobe and anaerobe
      bacterias and intensive care if necessary.

PMID- 9627446
TI  - Births, marriages, divorces, and deaths for October 1997.

PMID- 9627448
TI  - [The 'digital appendix'; an added value to published articles?].

PMID- 9627447
TI  - [Two cold legs].
AB  - Bilateral acute lower limb ischaemia is rare. Usually the diagnosis is based on
      clinical findings. In four patients, three women aged 51, 48, and 72 and a man
      aged 64 years, bilateral acute ischaemia of the lower limbs was diagnosed, due to
      different causes: arterial cardiac myxoma embolism, arterial thrombosis probably
      due to paraneoplastic coagulopathy, aortic dissection, and arterial thrombosis
      due to cardiac insufficiency, respectively. The management of these conditions
      includes restoring the circulation as soon as possible. Reperfusion can be
      achieved by thromboembolectomy or thrombolysis. In patients with underlying
      atherosclerosis angiography is useful, but time loss must be avoided. The outcome
      in patients with bilateral ischaemia of the lower limbs depends on the
      preoperative ischaemia time and the cardiac situation. The mortality varies
      between 20 and 50%.

PMID- 9627449
TI  - [The systolic heart murmur].
AB  - The abnormality most often found at physical examination of the heart is a
      systolic murmur. Aortic valve stenosis is a feared cause of systolic murmurs,
      which is also well evaluated with respect to the predictive value of physical
      diagnostic findings. Auscultatory characteristics of the murmur and palpatory
      findings of the carotid arteries show an acceptable predictive value and can be
      used by the general practitioner in the referral or reassurance of individuals
      with a systolic murmur. The different forms of the systolic murmur can be heard
      on the Internet address of this journal (http:@appendix.niwi. knaw.nl).

PMID- 9627450
TI  - [Digital imaging and robotics in endoscopic surgery].
AB  - The introduction of endoscopical surgery has among other things influenced
      technical developments in surgery. Owing to digitalisation, major progress will
      be made in imaging and in the sophisticated technology sometimes called robotics.
      Digital storage makes the results of imaging diagnostics (e.g. the results of
      radiological examination) suitable for transmission via video conference systems
      for telediagnostic purposes. The availability of digital video technique renders
      possible the processing, storage and retrieval of moving images as well. During
      endoscopical operations use may be made of a robot arm which replaces the camera
      man. The arm does not grow tired and provides a stable image. The surgeon himself
      can operate or address the arm and it can remember fixed image positions to which
      it can return if ordered to do so. The next step is to carry out surgical
      manipulations via a robot arm. This may make operations more patient-friendly. A
      robot arm can also have remote control: telerobotics. At the Internet site of
      this journal a number of supplements to this article can be found, for instance
      three-dimensional (3D) illustrations (which is the purpose of the 3D spectacles
      enclosed with this issue) and a quiz (http:@appendix.niwi. knaw.nl).

PMID- 9627451
TI  - [Drug treatment of Crohn's disease].
AB  - The medical management of Crohn's disease has changed in recent years, but the
      mainstay of treatment is still prednisone. A substantial fraction of steroid
      treated patients are refractory to therapy and addition of azathioprine or
      methotrexate has a corticosteroid-sparing effect and increases duration of
      remission. Controlled ileal release budesonide (9 mg daily) induces clinical
      remission in 60-70% of patients with Crohn's ileitis or right-sided colitis, and
      continued budesonide treatment has a finite effect on the duration of remission.
      The efficacy of mesalazine in active Crohn's disease is limited and high doses
      are required (4000 mg/day). The role of mesalazine in Crohn's disease in
      remission is disputed, and there is no evidence of a corticosteroid-sparing
      effect.

PMID- 9627452
TI  - [Clinical analysis of motion using multimedia technology].
AB  - In disabling orthopaedic and neurological disorders, in addition to clinical and
      imaging examination, observation of the motion is an important method of
      examination. It serves as a starting point for the motion analysis using digital
      video. In this way, muscle functions can be measured with the aid of a
      kinesiological EMG. Load on the joints of the lower extremities can be deduced
      from a projection of the foot reaction vector on the body. Combination of a video
      film of the motion (the gait) with measurement of the kinesiological EMG provides
      a motion analysis based on multimedia techniques. With modern personal computers,
      interactive examination of these digital data is simple. Three examples of this
      functionality can be viewed at the Internet site of this journal
      (http:@appendix.niwi.knaw.nl): the normal walking cycle, the active stabilization
      of the knee after an injury of the anterior cruciate ligament and the gait of a
      woman with cerebral palsy before and after orthopaedic surgery. Motion analysis
      using multimedia techniques makes it possible to analyse relationships between
      muscular and articular functions on the one hand and impaired motion on the other
      in a way that is meaningful to the clinician.

PMID- 9627453
TI  - [The organization and implementation of influenza vaccination in Groningen, 1993
      1996].
AB  - OBJECTIVE: To find out to what extent the recommendations from the standard
      'Influenza and influenza vaccination' of the Dutch association of general
      practitioners (NHG) were implemented by the GPs in the period 1993-1996. DESIGN:
      Descriptive questionnaire study. SETTING: Municipal Health Services Groningen,
      the Netherlands. METHOD: All GPs active in the province of Groningen were sent a
      questionnaire in the period 1993-1996. Practical support of GPs in organizing
      influenza vaccination was offered as a part of the project 'Preventie: maatwerk'
      (Prevention made to measure). RESULT: Automated selection of risk patients showed
      a distinct increase over the years. This increase was greatest in 1996,
      especially in rural practices. Inviting by personal letter, as recommended in the
      NHG standard increased to 48% in 1996. Not all GPs organized special vaccination
      office hours. An increasing number offered vaccination at other times as well. In
      urban municipalities, vaccine was available in the practice less often. Half the
      GPs reminded risk patients of the vaccination if they failed to appear. The
      recorded number of vaccinated patients in Groningen was 9.5% of the population in
      1994 (nation-wide: 10.8%), 10.8% in 1995 (nation-wide: 11.5%) and 15.4% in 1996
      (nation-wide: 15.2%). CONCLUSION: The attention for programmed prevention in
      general practice went together with an increase of activities regarding influenza
      vaccination. Regional monitoring of the influenza vaccination provides data with
      which the prevention programme can be improved.

PMID- 9627454
TI  - [Preconception counseling in family practice; a survey of 100 family physicians].
AB  - OBJECTIVE: To assess the awareness, opinions on desirability and preconditions
      such as special knowledge with regard to the concept of preconceptional health
      counselling among general practitioners. DESIGN: Descriptive. SETTING: General
      practices in the Groot Gelre district of the Dutch General Practitioners Society.
      METHOD: A representative sample of 100 general practitioners were asked by phone
      for permission to send a questionnaire; 89 out of the 94 general practitioners
      who were sent a questionnaire replied (response: 89%). RESULTS: Almost all
      general practitioners (88%) knew about the concept of preconceptional health
      counselling and most of them already gave some kind of preconceptional advice.
      93% considered preconceptional health counselling part of their job
      responsibility and 91% were prepared to give more preconceptional health care in
      the future. 53% of all general practitioners, however, indicated that they lacked
      sufficient knowledge to give adequate advice. The advantages of preconceptional
      health care were considered to outweigh possible disadvantages such as
      medicalization of pregnancy. CONCLUSION: The general practitioners knew about
      preconceptional health care and considered it part of their job. Many already
      provided preconceptional health care, although not in a structured way. General
      practitioners appeared to lack time and appropriate knowledge, which indicates a
      need for postgraduate training.

PMID- 9627455
TI  - [Compartment syndrome in both lower legs after prolonged surgery in the lithotomy
      position].
AB  - A 35-year-old man developed bilateral compartment syndrome in the lower legs
      after prolonged colorectal surgery in the lithotomy position. This complication
      of a prolonged non-physiological operation position is a rare event and the
      diagnosis is therefore often delayed, with sometimes serious irreversible
      neuromuscular damage. In this case the complication was successfully treated by
      four-compartment fasciotomy and forced diuresis (to prevent renal insufficiency
      caused by myoglobin nephrosis).

PMID- 9627456
TI  - ['Public health status and perspectives' 1997. I. Introduction].
AB  - The 'Public health status and forecasts' 1997 presents a comprehensive and
      integrated overview of health, disease and health care in the Netherlands, to
      which more than 250 experts contributed. On the basis of the findings, policy
      recommendations are formulated regarding target groups, planning, prevention,
      health care, monitoring and research.

PMID- 9627457
TI  - ['Public health status and perspectives' 1997. II. Developments in health
      status].
AB  - As a part of the report 'Public health status and forecasts' 1997 recent
      developments in the health status of the Dutch population and its determinants
      are described. Developments until the year 2015 are forecast on the basis of
      expected demographic and epidemiologic trends, according to expert opinions.
      Important findings are the unfavourable trends in lifestyle factors in
      adolescents and the expected increase by 25-60% in 2015 of the prevalence of
      diseases of old age like cancer, cardiovascular diseases, diabetes mellitus,
      dementia, chronic nonspecific lung diseases, visual and hearing impairments and
      diseases of the locomotor system.

PMID- 9627458
TI  - ['Public health status and perspectives' 1997. III. Health inequalities in the
      Netherlands].
AB  - The theme report 'Health inequalities' of the Dutch 'Public health status and
      forecasts' 1997 indicates that there are substantial health inequalities between
      population groups in the Netherlands, most notably with respect to socioeconomic
      status, but also in respect to other sociodemographic characteristics. It is
      expected that the numbers of people in several of these disadvantaged groups will
      increase. Improving the health status of disadvantaged groups can therefore
      theoretically produce great health gains.

PMID- 9627459
TI  - [Reference manager; a personal bibliography of references on the computer for
      consultation and word processing].

PMID- 9627460
TI  - [Iodine-125 implantation in localized prostate cancer].

PMID- 9627461
TI  - [Hormone replacement therapy after breast cancer].

PMID- 9627463
TI  - [The 102nd annual meeting of the Japanese Ophthalmological Society. Fukuoka,
      Japan. April 1-4, 1998. Abstracts].

PMID- 9627462
TI  - [The balance between health gains and effort exerted in population screening for
      breast cancer].

PMID- 9627464
TI  - [The 99th Congress of the Japanese Society of Otolaryngology. Sapporo, Japan. May
      21-23, 1998. Abstracts].

PMID- 9627465
TI  - [History and overview of neuro-immunology].

PMID- 9627466
TI  - [Etiology and physiopathology of multiple sclerosis].

PMID- 9627467
TI  - [Etiological mechanism and treatment of Guillain-Barre syndrome-- Campylobacter
      jejuni enteritis and the development of anti-ganglioside antibody preceding the
      syndrome].

PMID- 9627468
TI  - [Physiopathology and treatment of Fisher syndrome: participation of a specific
      antibody].

PMID- 9627470
TI  - [Physiopathology and treatment of vasculitic neuropathy].

PMID- 9627469
TI  - [Diagnosis and treatment of chronic inflammatory demyelinating polyneuropathy].

PMID- 9627471
TI  - [Physiopathology and treatment of myotonia and convulsion: Isaacs syndrome and
      stiff-man syndrome].

PMID- 9627472
TI  - [Physiopathology and clinical presentation of Crow-Fukase Syndrome].

PMID- 9627473
TI  - [Diagnosis and treatment of HAM].

PMID- 9627474
TI  - [Anti-ryanodine receptor antibody and the thymus gland in myasthenia gravis].

PMID- 9627475
TI  - [Immunopathology and treatment of polymyositis and dermatomyositis].

PMID- 9627476
TI  - [Paraneoplastic neurological syndromes. 1. Encephalopathy and peripheral
      neuropathy].

PMID- 9627477
TI  - [Paraneoplastic neurologic syndromes. 2. Lambert-Eaton myasthenic syndrome. 1)
      The molecular structure of calcium channel and immunology].

PMID- 9627478
TI  - [Paraneoplastic neurologic syndromes. 2. Lambert-Eaton myasthenic syndrome. 2)
      Anti-calcium channel antibody and clinical features].

PMID- 9627479
TI  - [Treatment of immunologic nervous system diseases by using anti-adhesion molecule
      antibodies].

PMID- 9627480
TI  - [Discussion: immunologic nervous system diseases investigated from the molecular
      level].

PMID- 9627481
TI  - [Case of malignant neuroleptic syndrome caused by an anti-depressive agent, later
      complicated by respiratory insufficiency and DIC].

PMID- 9627482
TI  - [Case of chronic tubulointerstitial nephropathy associated with idiopathic
      ductopenia].

PMID- 9627483
TI  - [Case of renal hypouricemia causing exercise-induced acute renal failure].

PMID- 9627484
TI  - [Case of familial amyloid polyneuropathy discovered at the development of
      hematemesis].

PMID- 9627485
TI  - [Recovery from septicemia caused by fecally identified Vibrio vulnificus and
      complicated by ulcerative colitis ].

PMID- 9627486
TI  - [Guanylin family, a new gastrointestinal peptide acting on the control of water
      NaCl metabolism].

PMID- 9627487
TI  - [Progress in imaging diagnosis of circulatory diseases].

PMID- 9627488
TI  - [Recurrence of ulcers and inflammation].

PMID- 9627489
TI  - [Quantitative PCR system].
AB  - We evaluated a real time quantitative PCR assay using dual-labeled fluorogenic
      probes for clinical application. Preliminary study using the house-keeping gene,
      beta-actin confirmed that this method was accurate and reproducible for the
      quantitative detection of the genes. The system also has merit with regard to the
      dynamic range of the starting target molecule determination. We then investigated
      DNA copies of cytomegalovirus (CMV) gene in vivo. The results demonstrated on
      association between the quantitation of CMV-DNA copies and clinical manifestation
      associated with CMV infection of immunodeficiency states or infantile hepatitis.
      It was also successful for quantitative estimation by RT-PCR. Namely, the assay
      made it possible to discriminate drug-sensitive leukemia cells from resistant
      cells based on the MDR1 gene and dCK gene. Real time quantitative PCR assay may
      be useful in a variety of clinical fields.

PMID- 9627490
TI  - [Analysis of genomic instability by fluorescence DNA sequencer].
AB  - Within the recent four years, there have been substantial advances in
      understanding the molecular pathogenesis of HNPCC. As one of the result of
      investigation, microsatellite instability has been observed in hereditary non
      polyposis colorectal cancer (HNPCC) and other sporadic cancers. Moreover, there
      is strong supporting evidence that mismatch repair genes play a role in HNPCC.
      Here, we present our investigational results and discuss possible molecular
      mechanisms governing DNA mutation and genomic instability, leading to the
      development of neoplasm. We investigated replication error (RER) of 4
      microsatellite markers (dinucleotide repeats) in 131 patients with colorectal
      cancer (10 met the criteria of HNPCC group B), using fluorescence-based DNA
      sequencer. We detected RER positivity (at more than two loci) in 12 of 131
      patients (9.2%). PCR-SSCP and direct sequencing of the mismatch repair genes,
      hMSH2 and hMLH1, revealed that two patients in HNPCC group B had germline
      mutations of hMSH2. The fluorescence-based techniques, such as the present RER
      analysis do not require radioactive materials and specialized rooms, and can
      easily be performed in a clinical laboratory.

PMID- 9627491
TI  - [Molecular diagnostics by automated systems].
AB  - Advent of molecular biology and biotechnology have realized and facilitated
      analyses for DNA or RNA sequences. New technological advances have led to the
      automation of major part of the assay process. Automated systems have been
      developed for amplification and detection of nucleic acid sequence for infectious
      agents, using polymerase chain reaction, ligase chain reaction, strand
      displacement amplification, transcription-associated amplification, and nucleic
      acid sequence-based amplification. Development of such automated systems are
      based on accumulation and integration of new molecular biotechnology. There has
      appeared a fully automated PCR system (COBAS AMPLICOR), which amplifies target
      nucleic acid sequence, captures the biotinylated and amplified products on
      oligonucleotide-coated paramagnetic microparticles, and detects the products with
      an avidin-horseradish peroxidase (HRP) conjugate. Automated systems provide
      improvement of not only labor efficiency but also assay accuracy. Contamination
      with the amplified products and difficulty in interpreting test results have been
      overcome with introduction of new technologies such as uracil N-glycosylase and
      positive internal control. Recently, the extraction of a specific sequence for
      hepatitis C virus (HCV) RNA has been automated, and the RNA can be specifically
      extracted from serum by hybridization with probe-coated paramagnetic
      microparticles, and then subjected to in vitro amplification. Automated systems
      for nucleic acid extraction from a variety of clinical specimens are now desired.
      To be practical, an automated system for each molecular diagnostic method must
      assure assay rapidity, quantification, quality control and cost effectiveness. It
      is also important to consider how to properly use or combine the molecular
      diagnostic methods for an efficient approach to the diagnosis of diseases.

PMID- 9627492
TI  - [Proliferation and differentiation of leukemic cells in acute myelocytic
      leukemia].
AB  - Acute myelocytic leukemia is characterized as a malignant disease with excessive
      accumulation of leukemic cells and deterioration of hematopoiesis. We studied the
      mechanism by which leukemic cells proliferated in patients. The indefinite growth
      of leukemic cells is supported by leukemic blast progenitors with a self-renewal
      capacity. Hematopoietic growth factors, such as granulocyte colony-stimulating
      factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF),
      interleukin-3 (IL-3) or stem cell factor (SCF), have been revealed to stimulate
      the growth of leukemic blast progenitors. Furthermore, leukemic cells themselves
      produce and secrete hematopoietic factors that stimulate leukemic blast
      progenitors. The so-called autocrine growth mechanism has been postulated to play
      an important role in the pathophysiology of acute myelocytic leukemia. Leukemic
      cells show terminal differentiation under certain circumstances. For example,
      leukemic cells differentiate to neutrophils or macrophages in suspension culture.
      Leukemic cells of erythroleukemia (FAB M6) differentiate to granulocytic and
      erythrocytic lineages. The mechanisms involved in the proliferation and
      differentiation of leukemic cells in acute myelocytic leukemia are discussed in
      the article.

PMID- 9627493
TI  - [Regulation of megakaryopoiesis and thrombopoiesis by thrombopoietin].
AB  - Thrombopoietin (TPO) is a major hematopoietic growth factor which regulates the
      production of megakaryocytes and platelets. Recent cloning of its c-DNA and
      availability of recombinant TPO have enabled us to examine the biological effects
      of TPO in various systems, including human platelets. In this review, we briefly
      describe the recent progresses made in the studies of TPO and its cognate
      receptor, c-Mp1.

PMID- 9627494
TI  - [Differentiation and maturation of erythroblasts].
AB  - Erythropoietin/receptor (EPO/EPOR) system is a pivotal regulator of
      erythropoiesis. Indeed, EPO-deficient and EPOR-deficient mice are embryonic
      lethal. The EPOR has two dominant forms, a full-length one (EPOR-F) and a
      truncated one (EPOR-T), by an alternative splicing mechanism of mRNA. The EPOR-T
      expresses abundantly in more immature erythroid progenitor cells. The EPOR-T acts
      as a dominant negative regulator of EPO-signals for proliferation and anti
      apoptosis in cell lines. Presumably, the EPOR-T forms a heterodimer with EPOR-F
      and results in inhibition of efficient EPO-signals. Transgenic mice over
      expressing the EPOR-T show an anemia and a severe defect in recovery from acute
      anemia. This result strongly suggests that the EPOR-T acts as a negative
      regulator for erythropoiesis also in vivo. It was reported that a large number of
      erythroid precursor cells die of apoptosis under physiological concentration of
      EPO in mouse. At higher EPO-concentration, these erythroid precursors escape from
      apoptosis and mature into erythrocytes. This mechanism might allow immediate
      supply of a large number of erythrocytes in case of acute anemia. In such
      mechanism, the EPOR-T might play an important role as a regulator of EPO-induced
      signals in erythroid cells.

PMID- 9627495
TI  - [Diagnosis of hemoglobinopathies].
AB  - The chemical identification of variant hemoglobins was largely overtaken by DNA
      analysis during the last decade, despite remarkable improvement and automation of
      individual procedures in conventional chemistry. DNA diagnosis has proved more
      versatile, covering both variant hemoglobin and thalassemia mutations, less labor
      demanding, and easier to learn. Protein chemistry is now reserved for some
      special problems such as post-translational modification (this problem would be
      covered much better by mass spectrometry), biosynthesis and stability, and
      pathologic physiology of selected abnormal hemoglobins. After introduction of DNA
      analysis during mid 1980's, the number of blood samples referred to our
      laboratory rapidly increased, mainly because of thalassemia traits in the
      differential diagnosis of microcytic anemia. Our experience during the past forty
      years and the present strategy for the rapid presumptive diagnosis of
      hemoglobinopathies and precise identification of mutations are briefly
      summarized.

PMID- 9627496
TI  - [Recent trends in protein structural studies].
AB  - Since the 1980's, structural studies of proteins have changed remarkably. It is
      currently possible to predict the entire amino acid sequence of a protein by the
      rapid and highly sensitive analysis of the nucleotide sequence of genomic DNA or
      cDNA encoding the protein. In the near future, the entire sequence of a protein
      may be predicted from a partial sequence just by searching a variety of databases
      now being constructed for many biological species. The predicted protein
      sequence, however, is the backbone structure of the precursor protein without
      post-translational modifications. Therefore, the major objectives of recent
      structural studies of proteins are directed to 1) rapid and sensitive
      confirmation of the predicted sequence and identification of those modifications
      present in mature proteins by newly developed mass spectrometry, 2) determination
      of the 3D structures of intact and mutant proteins isolated or expressed in
      cultured E. coli, yeast or animal cells using X-ray crystallography or NMR
      analysis, and 3) rapid prediction of the 3D structures of proteins utilizing
      protein databases. The "PROTEOME" project was proposed in 1998 to bring together
      all the data on the structure and function of mature proteins under international
      cooperation. The present paper summarizes such recent trends in protein
      structural studies.

PMID- 9627497
TI  - [Epitope analysis of anti-serum protein antibodies and its application for
      amyloidosis research].
AB  - To obtain antibodies specific to desired portions in proteins, synthetic peptides
      are widely used as immunogens, however, generated antibodies often react
      improperly with native proteins. Monoclonal antibodies (MoAb), epitopes of which
      are well defined, would be useful. In this review, we present epitope analysis
      and its application for immunohistochemical studies on four MoAbs against serum
      amyloid A(SAA), the serum precursor of fibrillar component in reactive amyloid
      deposits. Multipin-ELISA (enzyme-linked immunosorbent assay), the epitope mapping
      system which is based on reactivity with small amount of synthetic peptides
      immobilized on plastic pins, divided 13 clones of rat-mouse hybrid anti-SAA MoAbs
      into four. Two were determined epitopes as a portion around residue 18 and 30 of
      SAA while the other two could not be determined. These epitopes were analyzed
      using truncated recombinant SAA proteins, which were produced in E. coli, and
      determined as a portion around residue 90 and 100 (C-terminus), respectively.
      Negative immunohistochemistry of anti-SAA C-terminus MoAb for human reactive
      amyloid deposits suggests that SAA C-terminus is removed before or during amyloid
      deposition.

PMID- 9627498
TI  - [Detection and characterization of aberrant blood proteins and quantification of
      glycated hemoglobin by mass spectrometry].
AB  - Electrospray Ionization Mass Spectrometry can be applied to detect aberrant
      proteins using intact molecules. Direct examination of hemolysate might well
      facilitate rapid ascertainment of a variant hemoglobin (Hb) provided that the
      mass difference between normal and abnormal chains is larger than the resolution
      power of standard instruments (i.e. = 10 Da). We propose immunoprecipitation as a
      preparation method of plasma and cell proteins other than Hb prior to MS. Amino
      acid sequences of various variants detected by MS were determined by MS/MS. Some
      of these variants were new. These new variants were; 1: Hb Sagami[beta
      139(H17)Asn-->Thr]. 2: Hb Hokusetsu[beta 52(D3)Asp-->Gly]. 3: a variant
      transthyretin, amyloidogenic, [38Asp-->Ala]. 4: a variant transthyretin, non
      amyloidogenic, [101Gly-->Ser]. The abundance of ion peaks showed the approximate
      ratio of each component, which was in agreement with the ratio obtained by
      chromatography and by ESIMS in the analyses of glycated hemoglobin. Samples with
      low kidney function (BUN > 50 mg/dl, creatinine > 2.5 mg/dl) showed higher values
      of glycated Hb on routine HPLC than the MS method. Samples containing high
      carbamylated Hb might cause this discrepancy.

PMID- 9627499
TI  - [Sex and age distribution of patients with macroamylasemia found in the daily
      isoenzyme analysis].
AB  - We studied distributions of sex and age for 102 patients with macroamylasemia
      found in routine isoenzyme analysis. This study was based on a questionnaire to
      promote understanding of the clinical significance of macroamylase. More than
      half of the physicians received our report evaluated the information on
      macroamylase in the questionnaire. Macroamylasemia found in this study consisted
      of IgA type immunoglobulin in 92% and mostly had high activities in the serum.
      The back-ground of these patients with macroamylasemia were 10 cases of hepato
      biliary disease, 9 cases of diabetes mellitus, 8 cases of autoimmune disease and
      so on. The frequency of macroamylasemia in males was double than in females and
      age distribution was not significant in statistic analysis.

PMID- 9627500
TI  - [Determination of pyrazinamide susceptibility for Mycobacterium tuberculosis by
      use of Middlebrook culture media and comparison with results of pyrazinamidase
      test].
AB  - We developed a new test method to determine pyrazinamide (PZA) susceptibility for
      Mycobacterium tuberculosis in an acidified Middlebrook 7H9 broth (pH6.0), and
      evaluated in comparison with the agar proportion method of the National Committee
      for Clinical Laboratory Standards (NCCLS) M24-T and with pyrazinamidase assay.
      The test method is based on a culture in 4 ml of the modified Middlebrook 7H9
      broth containing 100, 200 and 400 micrograms PZA/ml, respectively. First, the
      cell suspension was adjusted to a McFarland #1 turbidity, and then diluted 1:10.
      After mixing, 0.1 ml of the diluted cell suspension was inoculated and incubated
      at 36 +/- 1 degrees C in an ambient air. After 7 day-incubation, the test broth
      was read in comparison with the growth control. When a significant growth at 100
      micrograms PZA/ml or an attenuated growth at 100 micrograms PZA/ml but a
      significant growth at 400 micrograms PZA/ml were observed, the test isolate was
      interpreted as being PZA-resistant. When PZA-susceptible and PZA-resistant ATCC
      reference strains were repeatedly tested, the results obtained were highly
      precise and accurate. A total of 65 clinical isolates were tested, the results
      indicating 95.4% of agreements with the agar proportion method and 90.8% with
      pyrazinamidase assay. There found six discrepant results of 13 resistant
      isolates; three were susceptible by the agar proportion and all the six were
      positive by pyrazinamidase assay. Accordingly, we can conclude that, in place of
      radiometric Bactec System, our newly developed test method is an accurate,
      practical, rapid and nonradiometric alternative to determine PZA susceptibility
      for M. tuberculosis in clinical mycobacteriology laboratories.

PMID- 9627501
TI  - [Identification of aneuploids in uncultured amniotic fluid cells by interphase
      fluorescence in situ hybridization].
AB  - We report the diagnosis of aneuploids in uncultured amniotic fluid cells by the
      use of interphase fluorescence in situ hybridization (FISH). About a dozen of
      cases was studied to detect chromosome aneuploids (trisomies 13, 18 and 21, and
      monosomy X), especially those in the perinatal period. Results of FISH
      experiments in each specimen were compared with those of conventional chromosome
      analysis, and showed no discrepancy between them in most cases. FISH analysis
      revealed that four 18-trisomies had two different cells, one of which showed two
      fluorescence signals and the other three signals, the result indicating a
      maternal cell contamination. Thus, special attention should be paid when FISH
      analysis is adopted to the diagnosis in uncultured amniotic fluid cells in order
      to avoid misdiagnosis that may originate in maternal cell contamination.

PMID- 9627502
TI  - [Treatment of HIV/AIDS. New possibilities result in new problems].

PMID- 9627503
TI  - [Effect of antibiotics on symptoms and complications of sore throat. Comments on
      a meta-analysis from the Cochrene database].

PMID- 9627504
TI  - [Non-invasive assessment of endothelial function].
AB  - Endothelial dysfunction is an early event in atherosclerosis preceding the
      formation of plaques. An important functional consequence of endothelial damage
      is reduced vasodilatory responses to a variety of pharmacological and
      physiological stimuli including reactive hyperaemia. Hitherto, endothelial
      function could only be assessed by invasive techniques, but a novel ultrasound
      based technique has recently been developed, which allows non-invasive evaluation
      of endothelial function in large systemic arteries such as the brachial artery.
      The technique is accurate, reproducible and able to differentiate between
      subjects with and without vascular dysfunction. Impaired endothelial function has
      been documented in young and adult individuals with various vascular risk factors
      including cigarette smoking, diabetes mellitus, hypercholesterolaemia, and
      homocystinuria. A good correlation has been found between both the presence of
      atherosclerotic lesions and endothelial function in the coronary arteries and the
      brachial artery. The method may help in identification of individuals with early
      vascular changes and thereby make risk factor modification possible at a very
      early stage of the atherosclerotic process. It may furthermore serve as a tool to
      monitor the impact of prevention and intervention on arterial damage.

PMID- 9627505
TI  - [Child psychiatric in-patient treatment].
AB  - This article describes the Danish part of a multinational epidemiological point
      prevalence study concerning child psychiatric in-patient treatment, which aims to
      describe different kinds of treatment methods used in child psychiatric in
      patient care. The study includes all 10 child psychiatric in-patient units in
      Denmark. Data on psychiatric treatment modalities were collected by means of a
      questionnaire in spring 1990 on 192 children, which included all of the actual in
      patients (100%). Primary caretaking was the main treatment method (100%),
      individual psychotherapy was offered to one third, as was family therapy. Eight
      percent were medicated, 6% with psychoactive drugs. The study showed that
      medication in child psychiatric in-patient care was rare, and was never the only
      treatment method. A range of psychotherapeutic methods were used.

PMID- 9627506
TI  - [Community psychiatry in Copenhagen. Adaptation to increased needs].
AB  - The purpose was to show the changes taking place in a community mental health
      centre where the need for treatment definitely increased compared to the
      available resources. The reason for this was an increase in size of the district
      covered. Data was recorded in a database. All patients in treatment and received
      during the years 1994 and 1995 were registered. The years 1990-92 were used for
      comparison. The necessary changes in organisation are described. The number of
      patients received decreased and the percentage with serious mental illness
      increased. After visitation the population which received treatment at the centre
      was dominated by patients with chronic psychosis. More consultations were given
      in the patients' homes. The retention of patients decreased. It is concluded that
      only half of the people in the district with serious mental illness were
      receiving treatment and only by increasing the amount of staff would it be
      possible to get the rest into treatment. The intake of other diagnostic groups
      should only be discussed after these steps are taken.

PMID- 9627507
TI  - [Skin symptoms on the hands of female house-cleaning personnel].
AB  - Skin symptoms on the hands were studied in questionnaire-based studies conducted
      in 1989 and 1991 among female cleaners employed at Danish nursing homes, schools
      and offices. Eleven hundred and sixty-six participated in 1989 and 1011 of them
      participated in 1991. The average age was 45 years and the average length of five
      employed as a cleaner was ten years. Forty-three percent reported to have had at
      least one out of four skin symptoms during a one year period. Seventy percent
      reported improvement during week-ends and holidays. A positive correlation was
      found between hours per week spent with wet hands and skin symptoms. During the
      follow-up period the risk of developing skin symptoms was higher in the group who
      remained cleaners compared with the group who left the cleaning job. Similarly,
      the prognosis was better in the group which left the cleaning job compared with
      the group which remained cleaners. There is a future need to develop and
      implement new work organisation and cleaning methods to reduce the time spent
      with wet hands.

PMID- 9627508
TI  - [Trade-specific occurrence of occupational hand injuries].
AB  - The purpose of the investigation was to estimate the trade-specific incidence of
      occupational hand injuries, to estimate the trade-specific cumulative incidence
      proportion and to investigate whether age, gender and trade each were independent
      risk-indicators for occupational hand injuries. In a retrospective design, 823
      patients with occupational hand injuries treated at Odense University Hospital
      were included in the investigation. The population at risk was 96,512 persons
      engaged in active employment within the municipality of Odense. The overall
      incidence of occupational hand injuries was estimated to 1.7 percent and 0.3
      percent for significant injuries. The incidences in the production- and building
      industries were significantly higher than the incidence in the service
      industries. Gender and occupation were both found to be independent risk
      indicators for occupational hand injuries, age only for the minor injuries.
      Occupational hand injuries seem to be so common, that prevention-trials should
      continuously be intensified. The target-groups should firstly be employees in the
      production industries, however prevention-trials directed against specific age-
      and gender behaviour patterns should also be considered.

PMID- 9627509
TI  - [Fatal accidents in house fires. The most significant causes, such as smoking and
      alcohol abuse, multiplied by four the incidence during the last 40 years].
AB  - A population-based descriptive investigation of housefire accidents in Denmark
      was carried out for the two five year periods 1953-58 and 1988-93, based on death
      certificates, police reports and autopsy reports. The number of deaths due to
      housefire accidents in Denmark has increased (1953-58: 136 (66 men and 70 women),
      1988-93: 363 (212 men and 150 women), mostly due to an increase in tobacco
      smoking related fire accidents. In 1988-93 the three common causes of housefire
      deaths were tobacco-smoking, often in combination with alcohol intoxication or
      handicap (51%), cooking-accidents (10%) and accidents with candles (9%). The
      largest risk groups were chronic alcoholics, handicapped and elderly people. In
      conclusion, warnings should be issued against smoking in bed and use of loose
      fitting clothing while cooking on an open fire. Protective aprons and devices for
      use while smoking, self-extinguishing cigarettes and use of fireproof materials
      in furniture and clothing may prevent ignition. Smoke-alarms may secure early
      warning.

PMID- 9627510
TI  - [Bile acid therapy vs. placebo before and after extracorporeal shock wave
      lithotripsy of gallbladder stones].
AB  - The aims of the project were to study the effects of bile acid therapy on the
      fragmentation rate of cholesterol gallbladder stones by extracorporeal shock wave
      lithotripsy (ESWL) and on the clearance of fragments after ESWL. One hundred and
      two patients with biliary pain, between one and five radiolucent gallbladder
      stones, and a gallbladder with a patent cystic duct were randomized to three
      weeks of double-blind treatment with bile acids (ursodeoxycholic acid 500 mg and
      chenodeoxycholic acid 500 mg per day) or placebo before ESWL. After successful
      fragmentation by ESWL (largest fragment (< or = 5 mm) the patients were re
      randomized to six months double-blind therapy with bile acids or placebo. The
      endpoint of pre-ESWL bile acid/placebo therapy was the proportion of patients
      having a successful fragmentation after < or = 3 sessions of ESWL. After post
      ESWL bile acid/placebo therapy success was defined as a gallbladder cleared of
      fragments. Ninety-nine patients carried out three weeks of pre-ESWL treatment.
      There was no statistically significant difference in fragmentation rate between
      the two groups. After six months of post-ESWL therapy, 12 of 49 patients (24%)
      receiving bile acids had cleared the fragments from their gallbladder compared to
      5 out of 50 patients (10%) who received placebo (p = 0.10). There was no
      significant difference in the occurrence of pain between the two groups. In
      conclusion, ESWL with or without adjuvant bile acid does not seem to be an
      attractive therapy for patients with uncomplicated symptomatic gallstone disease.

PMID- 9627511
TI  - [Resistance of Helicobacter pylori to clarithomycin].
AB  - Resistance to clarithromycin in H. pylori has emerged in a number of countries.
      We present the first documented case of H. pylori resistance to clarithromycin in
      Denmark. This follows an increase in the use of clarithromycin as part of the
      treatment of H. pylori in the most recent years in Denmark. The need for
      culturing and susceptibility testing in H. pylori is emphasized.

PMID- 9627513
TI  - [To scan--or not to scan?].

PMID- 9627514
TI  - [Significance of breast feeding after organ transplantation].

PMID- 9627512
TI  - [Anti-inflammatory treatment of sepsis--is it efficient?].

PMID- 9627515
TI  - [Reduced responsibility--but whose?].

PMID- 9627516
TI  - [White coat methods--simple, inaccurate and full of bias].

PMID- 9627518
TI  - Re: CJ Green, DC Hadorn, K Bassett, A Kazanjian. Anticoagulation in chronic
      nonvalvular atrial fibrillation: a critical appraisal and meta-analysis.
      1997;13:811-5.

PMID- 9627517
TI  - WHO Expert Committee on Leprosy.
AB  - Considerable progress has been made in the fight against leprosy during the past
      10-15 years, following the introduction of multidrug therapy (MDT) regimens and
      the establishment of the goal of eliminating leprosy as a public health problem
      by the year 2000. Current estimates indicate that there are about 1.15 million
      cases of leprosy in the world, compared with 10-12 million cases in the mid
      1980s. This report presents the conclusions of a WHO Expert Committee convened to
      review the global leprosy situation and the technology available for eliminating
      the disease, to identify the remaining obstacles to reaching the goal of
      eliminating leprosy as a public health problem, and to make appropriate
      recommendations for the future on technical and operational matters. The current
      status of leprosy elimination is discussed, and the various antileprosy drugs are
      reviewed, including the most recently available drugs. On the basis of field
      trials and clinical studies, the Committee concludes that a single dose of a
      combination of rifampicin, ofloxacin and minocycline is an acceptable and cost
      effective alternative regimen for the treatment of single-lesion paucibacillary
      leprosy, and that the duration of the current MDT regimen for multibacillary
      leprosy could possibly be shortened to 12 months. The Committee points out the
      need for improved management of reactions and neuritis and prevention of leprosy
      related disabilities and impairments, and recommends that antileprosy activities
      should become an integral part of general health services and should involve
      communities to the fullest extent possible.

PMID- 9627519
TI  - Re: CJ Green, DC Hadorn, K Bassett, A Kazanjian, Anticoagulation in chronic
      nonvalvular atrial fibrillation: a critical appraisal and meta-analysis.
      1997;13:811-5.

PMID- 9627520
TI  - Coverage of drug costs: reference-based pricing.
AB  - Since 1985, British Columbia has used reference-based pricing (RBP) as a basis
      for reimbursement of the cost of an increasing number of drugs. Under this policy
      the costs of certain drugs are reimbursed at a level determined by the price of
      the lowest priced drug of equal efficacy in the same category. A recent position
      paper of the Canadian Cardiovascular Society has roundly criticized this policy.
      The principal grounds for criticism are that the policy is not 'evidenced based',
      that it is ineffective in that it does not lower health care costs, and that it
      contravenes the principals of equity and accessibility. These claims were
      examined and determined to be ill founded. Because the British Columbia
      experiment seems to be a reasonable approach to restraining drug costs it should
      be continued and monitored closely. In this way, real evidence of the impact of
      RBP on health and health care costs in the context of the Canadian health care
      system can be obtained.

PMID- 9627521
TI  - The Canadian Cardiovascular Society and reference-based drug pricing.

PMID- 9627522
TI  - Histological and morphometric analyses of early and late aortocoronary vein
      grafts and distal anastomoses.
AB  - BACKGROUND: Aortocoronary vein grafts develop fibromuscular intimal hyperplasia
      within the first year of implantation. Tissue remodeling may promote development
      of graft atherosclerosis and thrombosis. Angiographic studies show that human
      aortocoronary vein grafts in situ for one or more years become stenosed,
      preferentially at the distal anastomosis versus the body or trunk of the graft or
      at the proximal anastomosis. Previous studies have not reported morphological
      data on the nature and distribution of intimal lesions around the distal
      graft/artery anastomoses. OBJECTIVE: To examine and quantify histological and
      morphometric changes within the intima of 27 aortocoronary vein grafts and their
      distal anastomoses. METHODS: Seventy-two hearts obtained at autopsy and one at
      heart transplantation were examined, photographed and fixed in 10% buffered
      formaldehyde solution. Three to seven 3 mm long segments of grafts and their
      distal anastomoses were sectioned, stained and examined by light microscopy.
      RESULTS: Eleven early grafts were implanted for six weeks or less, and they
      showed significant cellular hyperplasia mainly at the suture line. In 16 late
      grafts in situ 1.5 to 15 years, the degree of fibromuscular intimal thickening
      was greatest on the hood and at the suture line, whereas on the floor of the
      native artery and in the graft body the degree of thickening was approximately
      one-third and two-thirds, respectively, that seen on the hood. CONCLUSIONS:
      Stenosis of aortocoronary vein grafts at their distal anastomosis is likely
      related to the preferential development of intimal thickening on the hood of the
      graft and at the suture line. Because fibromuscular intimal hyperplasia has been
      reported to play a role in the development of atherosclerosis and thrombosis in
      the body of vein grafts, this focal hyperplasia at the distal anastomosis may
      also play a role in vein graft failure.

PMID- 9627523
TI  - Effects of short-term altitude training and tapering on left ventricular
      morphology in elite swimmers.
AB  - Short or long-term athletic training has been associated with left ventricular
      (LV) morphological adaptations, including increases in wall thickness, cavity
      dimension and estimated LV mass. A limitation of previous studies assessing the
      'athlete heart' was that exercise training was performed at sea level. Since the
      1968 Olympic summer games a popular method of maximizing athletic performance has
      been to use altitude training (AT) as a means of improving sea level performance.
      However, the effects of short term AT and taper training on LV morphology have
      not been well studied. Based on this limitation, the effects of three weeks of
      intense AT (1848 m) or low level control training (CT) (1050 m) followed by two
      weeks of taper training were investigated in 15 elite swimmers between 16 and 21
      years of age. Short term AT or CT training followed by two weeks of taper
      training was not associated with alterations in LV diastolic cavity dimension (AT
      pre 53.3 +/- 2.8 mm versus post 52.6 +/- 4.3 mm; CT pre 52.9 +/- 3.7 mm versus
      post 51.2 +/- 4.0 mm), ventricular septal wall thickness (AT pre 9.6 +/- 1.0 mm
      versus post 9.4 +/- 1.1 mm; CT pre 8.4 +/- 1.2 mm versus post 8.6 +/- 1.1 mm),
      estimated LV mass (AT pre 186.4 +/- 45.8 g versus post 190.0 +/- 48.2 g; CT pre
      159.1 +/- 35.8 g versus post 160.1 +/- 40.8 g) or fractional shortening (AT pre
      36.8 +/- 3.5% versus post 34.8 +/- 2.7%; CT pre 32.6 +/- 5.0% versus post 32.8 +/
      4.7%). However, a main time effect, independent of training intervention, was
      observed for posterior wall thickness (pre 8.7 +/- 1.4 mm versus post 9.3 +/- 1.1
      mm, P < 0.05). Therefore, with the exception of posterior wall thickness, short
      term AT followed by two weeks of taper training appears not to be associated with
      alterations in LV morphology or systolic function.

PMID- 9627524
TI  - Comparative effects of felodipine ER, amlodipine and nifedipine GITS on 24 h
      blood pressure control and trough to peak ratios in mild to moderate ambulatory
      hypertension: a forced titration study.
AB  - OBJECTIVE: To evaluate the 24 h antihypertensive efficacy and duration of action
      of felodipine extended release (ER) in comparison with two other long acting
      dihydropyridine calcium antagonists, amlodipine and nifedipine gastrointestinal
      therapeutic system (GITS), in patients with mild to moderate essential
      hypertension substantiated by ambulatory blood pressure (BP) monitoring. DESIGN:
      Randomized, forced titration, parallel group study. Clinic BP was measured at
      every patient's visit, and 24 h ambulatory BP was monitored at baseline and at
      the end of each dose-titration period. SETTING: Single centre: hypertension
      research unit in Quebec City, Quebec. PATIENTS: There were 89 patients enrolled
      into the study. Eighty-four eligible patients were randomized, and 83 completed
      the study and were included in the final efficacy analysis. INTERVENTIONS:
      Following a two-to four-week washout period (baseline), patients were randomly
      allocated to receive felodipine ER 5 mg, amlodipine 5 mg or nifedipine GITS 30 mg
      for four weeks (low dose). All study patients had their daily dose doubled to
      felodipine ER 10 mg, amlodipine 10 mg or nifedipine GITS 60 mg for a further four
      weeks (high dose). MAIN RESULTS: Significant (P < 0.001) and similar changes from
      baseline in clinic BP were observed in all treatment groups for low and high
      doses. Ambulatory BP profiles showed comparable blood pressure reductions with
      felodipine ER and amlodipine, and a trend towards a lesser reduction with
      nifedipine GITS during 24 h, daytime and night-time periods. BP loads were
      similarly reduced with the three treatments. Trough to peak ratios (T:Ps) were
      calculated from 24 h ambulatory BP curves according to two different approaches:
      for diastolic and systolic BP, respectively, the global approach produced T:Ps of
      0.49 and 0.50 with felodipine ER 5 mg; 0.50 and 0.34 with felodipine ER 10 mg;
      0.70 and 0.60 with amlodipine 5 mg; 0.88 and 0.82 with amlodipine 10 mg; 0.65 and
      0.55 with nifedipine GITS 30 mg; 0.68 and 0.53 with nifedipine GITS 60 mg. T:Ps
      in the individual approach were 0.07 and 0.10 with felodipine ER 5 mg; 0.23 and
      0.31 with felodipine ER 10 mg; 0.22 and 0.31 with amlodipine 5 mg; 0.45 and 0.58
      with amlodipine 10 mg; 0.27 and 0.31 with nifedipine GITS 30 mg; and 0.24 and
      0.40 with nifedipine GITS 60 mg. CONCLUSION: There was no evidence in this study
      of a difference among felodipine ER, amlodipine and nifedipine GITS in lowering
      ambulatory or clinic BP. Treatment based on ambulatory BP may be preferable to
      treatment guided by T:Ps because ambulatory BP is firmly established as a
      predictor of cardiovascular risk. Furthermore, there is no consensus on how to
      calculate T:Ps, and different methods of calculation may give divergent results.

PMID- 9627525
TI  - Resting muscle sympathetic nerve activity does not predict duration of symptom
      limited submaximal exercise in young patients with dilated cardiomyopathy.
AB  - OBJECTIVE: To determine whether increased sympathetic vasoconstrictor drive to
      the calf in heart failure is associated with reduced symptom-limited submaximal
      exercise performance. DESIGN: Blood pressure, heart rate and peroneal muscle
      sympathetic nerve activity (MSNA) were recorded during rest and before symptom
      limited treadmill exercise at 70% of resting heart rate reserve for up to 45
      mins. PATIENTS: Thirteen young patients with dilated cardiomyopathy (age 36 +/- 2
      years). RESULTS: MSNA (45 +/- 6 bursts/min) was more than double the level
      documented in an age-, sex- and weight-matched group of normal subjects studied
      under identical baseline conditions. Patients with ventricular dysfunction
      exercised for 30 +/- 3 mins on average, but exercise distance and duration were
      independent of resting MSNA. CONCLUSIONS: In young patients with dilated
      cardiomyopathy, sympathetic nerve traffic to the calf vascular bed, measured at
      rest, does not predict the distance or duration of symptom-limited submaximal
      treadmill exercise.

PMID- 9627526
TI  - Thromboembolic prophylaxis in 3575 hospitalized patients with atrial
      fibrillation. The Clinical Quality Improvement Network (CQIN) Investigators.
AB  - OBJECTIVE: To define contemporary utilization patterns of anticoagulant and
      antiplatelet therapy for thromboembolic prophylaxis in atrial fibrillation (AF).
      DESIGN: Retrospective medical records audit of patients admitted in 1993 and
      1994. SETTING: Twelve Canadian hospitals. PATIENTS: Three thousand, three hundred
      and seventy-five consecutive patients with AF; 1570 females and 2005 males. The
      mean age was 72 years; 1353 patients were younger than 70 years and 2222 were
      aged 70 years and older. MEASUREMENTS AND RESULTS: Overall, 1188 (33%) of the
      3575 patients received no prophylaxis, 852 (24%) were treated with warfarin
      alone, 1247 (35%) received acetylsalicylic acid (ASA) alone and 288 (8%) received
      both drugs. The pattern of medication use did not change appreciably when
      possible contraindications to warfarin or ASA therapy were considered. Among the
      331 AF patients with valvular heart disease and no contraindications to
      thromboembolic prophylaxis, 65 (20%) received neither treatment, 181 (55%)
      received warfarin therapy alone, 46 (14%) received ASA alone and 39 (12%)
      received both. Among the 2199 AF patients with nonvalvular heart disease and no
      contraindications, 823 (37%) did not receive either therapy, 677 (31%) received
      ASA alone, 504 (23%) received warfarin alone and 195 (9%) received both. Elderly
      and female patients were less likely to receive thromboembolic prophylaxis.
      CONCLUSIONS: Anticoagulation and antiplatelet prophylaxis in AF appears to be
      less than optimal. Although concerns about bleeding may be one reason
      thromboembolic prophylaxis is so unevenly and incompletely applied, it will be
      important to determine the reasons for this practice and to develop effective
      strategies in order to enhance the process of care and patient outcomes.

PMID- 9627527
TI  - Predictors of early mortality after heart transplantation: the Canadian
      transplant experience from 1981 to 1992. The CASCADE Investigators. Canadian
      Study of Cardiac Transplant Atherosclerosis Determinants.
AB  - OBJECTIVE: To determine risk factors for early death following transplantation in
      the Canadian heart transplant experience. METHODS: A retrospective multicentre
      study of the Canadian experience in heart transplantation was performed to
      evaluate the role of risk factors of early death within 30 days following
      transplantation. Eight hundred and thirty-three patients older than 15 years
      underwent cardiac transplantation between 1981 and 1992 in 10 centres across
      Canada. The association between risk factors and early mortality was analyzed
      with a multivariate logistic model to examine simultaneously the effect of all
      risk factors. RESULTS: Seventy-eight patients (9%) died during the first month
      following transplantation. Recipient age (P = 0.549), sex (P = 0.554) and body
      mass (P = 0.313) had no effect. Baseline pulmonary vascular resistance (P <
      0.001) and systolic pulmonary pressure (P = 0.021) before transplantation were
      related to early death. Older donors (P = 0.027) were associated with a higher
      rate of early death but there was no relation with donor sex (P = 0.597), body
      mass (P = 0.413), blood group (P = 0.227) and ischemic time (P = 0.309). Patients
      with pulmonary vascular resistance of 6 or greater (Wood units) and donors older
      than 50 years had relative risks of early death five and two times, respectively,
      those of patients without these risk factors. CONCLUSION: Patient survival
      averaged 91% one month following transplantation in the Canadian experience
      between 1981 and 1992. The two predictors most strongly correlated with early
      death were elevated pulmonary vascular resistance at baseline and older donors.

PMID- 9627528
TI  - Lipoprotein lipase gene mutations in coronary artery disease.
AB  - BACKGROUND: Genetic lipoprotein disorders are frequently associated with
      premature coronary artery disease (CAD). Functional mutations of the lipoprotein
      lipase (LPL) gene are associated with altered plasma lipoprotein profiles and are
      relatively common in French Canadians. OBJECTIVE: To investigate the prevalence
      of LPL gene mutations in a group of patients with premature CAD and in a healthy
      control group. METHODS: A total of 636 subjects (337 [82% men] with
      angiographically documented CAD and 299 controls [63% men]) were examined for the
      presence of mutations LPL(Gly188-->Glu), LPL(Pro207-->Leu), LPL(Asp250-->Asn) and
      LPL(Asn291-->Ser) of the LPL gene. These mutations represent over 97% of LPL
      mutations in familial hyperchylomicronemia in Quebec. RESULTS: The prevalence of
      heterozygosity for defective LPL alleles was eight of 337 (2.4%) in the CAD group
      and five of 299 (1.7%) in the control group (chi(2) = 0.118, P = 0.73; power [P]
      for alpha = 0.05, P = 0.60). In the six CAD patients heterozygous for LPL(Asn291-
      >Ser), fasting plasma lipoprotein lipid levels did not differ significantly from
      those of the rest of the CAD group or markedly from those of control subjects.
      The two CAD patients heterozygous for the LPL(Gly188-->Glu) mutation, however,
      had hypertriglyceridemia and low plasma high density lipoprotein levels. No CAD
      or control subjects were identified with the LPL(Pro207-->Leu) or LPL(Asp250-
      >Asn) alleles. CONCLUSIONS: In this selected population of premature CAD
      subjects, the prevalence of heterozygosity for defective LPL alleles was slightly
      higher (but not significantly so) than that in a group of healthy subjects. The
      LPL(Gly188-->Glu) and LPL(Asn291-->Ser) mutations may confer genetic
      susceptibility to premature CAD in a small number (approximately 2.4%) of
      patients; overall these four LPL alleles do not appear to contribute
      significantly to CAD risk in French Canadians.

PMID- 9627529
TI  - The efficacy and safety of combination warfarin and ASA therapy: a systematic
      review of the literature and update of guidelines.
AB  - The English-language literature was systematically reviewed to clarify the role
      of combination antithrombotic therapy with warfarin and acetylsalicylic acid
      (ASA) versus monotherapy with either agent, including data from several recently
      published trials. Sixteen published studies with evaluable efficacy and/or safety
      data were identified. For patients with prosthetic heart valves at high risk of
      thromboembolism, combined warfarin and ASA therapy may be beneficial compared
      with warfarin alone. Combination therapy may also be used for primary prevention
      in patients at high risk for ischemic heart disease, although the expected
      benefits are small. Evidence does not support the use of combined antithrombotic
      therapy in patients with established ischemic heart disease, ischemic stroke,
      coronary artery bypass grafts or atrial fibrillation. Combination therapy is
      associated with an increased risk of minor and major bleeding. The highest dose
      of ASA that can be recommended in combination with warfarin is 100 mg daily.

PMID- 9627530
TI  - The Canadian Cardiovascular Society--the first and the next 50 years.

PMID- 9627531
TI  - Cell therapy to repair broken hearts.
AB  - Current therapeutic options for myocardial infarction include medical therapy, of
      proven but limited benefit, and various surgical options, which have either
      restricted applicability or unproven benefit. New cellular-based therapeutic
      strategies are being developed in response to the shortcomings of available
      treatments. These include attempts to reinitiate cardiomyocyte proliferation in
      the adult, conversion of fibroblasts to contractile myocytes and transplantation
      of myocytes into injured myocardium. The development and current status of these
      techniques and their relative advantages, problems remaining to be solved and
      potential clinical applications are reviewed.

PMID- 9627532
TI  - Magnesium in acute myocardial infarction: still an open question.
AB  - Many activities of magnesium have justified randomized controlled trials of its
      role in acute myocardial infarction (AMI), which have shown reduction of short
      term mortality by 25% to over 50%. The Fourth International Study of Infarct
      Survival (ISIS-4) megastudy failed to confirm these findings, and, based on
      analysis of pooled findings, it was concluded that magnesium has no place in
      treatment of AMI. The fixed effects statistical model employed in ISIS-4 for
      evaluation of pooled data is inappropriate because the studies were not
      homogeneous. Among the differences between the earlier studies and the megatrial,
      the most significant was the time at which magnesium infusions were started
      relative to the time of reperfusion. Animal studies have shown that magnesium is
      protective only if present before or at the time of reperfusion. Unlike in
      earlier trials, in which magnesium infusions were started soon after the ischemic
      event or simultaneously with a lytic agent, in ISIS-4 magnesium treatment was
      withheld until after iatrogenic or spontaneous reperfusion occurred. This can
      explain poor therapeutic results in ISIS-4, but not the hypotension and
      bradycardia encountered in a minority of patients in that study. Dosage
      difference alone cannot explain this, even though the amounts given in the small
      studies were 40% to 25% less than that in ISIS-4, because the dose used in the
      Second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2) was only
      slightly lower than that used in ISIS-4. Administration of high dose magnesium
      with an angiotensin-converting enzyme inhibitor (which spares magnesium) or the
      vasodilating oral nitrate in arms of ISIS-4 may have contributed to adverse
      effects of hypermagnesemia. Also, the very low mortality rate of controls in ISIS
      4 suggests that the patients may have been at relatively low risk, and it is in
      high risk patients that magnesium has been shown to be most effective. A large
      scale study of magnesium in such patients is being started.

PMID- 9627533
TI  - Torsade de pointes with sotalol overdose treated successfully with lidocaine.
AB  - Torsade de pointes is a polymorphic ventricular tachyarrhythmia associated with a
      long QT interval. The prognosis is excellent if torsade is recognized early. In
      the acquired long QT syndrome, measures should be taken quickly to identify and
      correct all predisposing conditions and to treat or prevent torsade. Established
      treatments of acquired torsade are magnesium bolus, electrolyte replacement,
      isoproterenol infusion and cardiac pacing. Sotalol overdose causing torsade is
      reported in which lidocaine appears to have suppressed an episode of torsade as
      well as prevented further episodes. Current understanding of the
      electrophysiological mechanisms of torsade and lidocaine, a review of the
      literature and the author's experience indicate that lidocaine is a potentially
      useful therapy in torsade.

PMID- 9627534
TI  - Beyond LDL-cholesterol: can further reductions in CAD risk be achieved by
      considering triglycerides?

PMID- 9627535
TI  - LDL-cholesterol: a risk factor for coronary artery disease--from epidemiology to
      clinical trials.
AB  - Discussion of potential strategies to modify lipids and lipoproteins other than
      low density lipoproteins (LDLs) should first recognize the convincing evidence in
      favour of the identification and aggressive treatment of elevated LDL cholesterol
      (LDL-C) levels in patients with established cardiovascular disease. Elevated LDL
      C level is one of the few risk factors for which there is evidence of involvement
      in every pathophysiological step of the development of cardiovascular disease.
      Longitudinal studies have established the role of LDL-C as a risk factor for
      cardiovascular disease incidence, recurrence and fatal outcome. Clinical trials
      and economic analyses have proven that aggressive treatment of elevated LDL-C in
      patients at high risk can prevent cardiac events with excellent cost
      effectiveness.

PMID- 9627536
TI  - The unstable atheromatous plaque.
AB  - Because the consequences of ischemic vascular disease are projected to be the
      leading cause of morbidity in the next century, it is critical to continue to
      develop preventive strategies and therapies for unstable vascular syndromes. A
      great deal has been learned about the natural history of atherosclerosis in the
      past decade, and it is now widely accepted that unstable atheroma and subsequent
      plaque rupture is a leading cause of acute myocardial infarction. However, recent
      studies indicate that plaque rupture may be a common and important cause of many
      cardiovascular diseases in addition to acute myocardial infarction. Available
      data indicate that lipid-rich pools and thin fibrous caps combine to establish
      high mechanical stresses in the lesion. In addition, active extra-cellular matrix
      degradation at these locations causes the fibrous cap to rupture at these
      locations. The pathophysiology of plaque rupture causing myocardial infarction is
      reviewed. Also, recent exciting data that suggest that prevention of plaque
      rupture may have dramatic and unforeseen clinical benefits are discussed.

PMID- 9627537
TI  - Plasma triglyceride as a risk factor for cardiovascular disease.
AB  - OBJECTIVES: To determine whether cardiovascular disease can be predicted from
      plasma triglyceride levels independent of high density lipoprotein (HDL)
      cholesterol levels. DATA SOURCES AND STUDY SELECTION: Seventeen prospective
      population-based studies, ranging in publication date from 1965 to 1994, were
      selected based on uniform criteria. Among the studies, 16 were conducted in men,
      comprising data for more than 46,000 men, with an average follow-up period of
      more than eight years. The data from women came from five studies, including
      nearly 11,000 women with an 11-year average follow-up. DATA EXTRACTION: The meta
      analysis protocol comprised the following steps: estimating the relative risk of
      triglyceride for each individual study; standardizing the relative risks to a 1
      mmol/l increase; estimating the variance and weighting relative risks by the
      inverse of the variance, and estimating the summary relative risk by averaging
      the weighted relative risks. DATA SYNTHESIS: Among studies of men, relative risks
      ranged from 1.1 to 2.0, and the summary relative risk was 1.32 (P < 0.05). All
      five studies of women were statistically significant, with relative risks ranging
      from 1.7 to 2.0. The summary relative risk was 1.76, higher than that for men,
      indicating a 76% increase in risk for women. For the studies among men in which
      HDL cholesterol data were available, multivariate adjusted relative risk was
      attenuated to 1.14 but was still statistically significant. Although only two
      studies of women included HDL cholesterol adjustments, the summary relative risk
      for triglyceride remained statistically significant, with a value of 1.37.
      CONCLUSIONS: When all available data are taken into account, increased
      triglyceride level is a risk factor for cardiovascular disease, independent of
      HDL cholesterol level. Clinical trials are urgently needed to determine whether
      lowering plasma triglyceride levels reduces subsequent risk of cardiovascular
      disease.

PMID- 9627538
TI  - Postprandial lipemia: emerging evidence for atherogenicity of remnant
      lipoproteins.
AB  - Patients with coronary artery disease (CAD) often have increased postprandial
      triglyceride levels compared with healthy control subjects, and it has been
      demonstrated that plasma triglyceride concentration in the fed state is an
      independent predictor of CAD. Increased postprandial triglyceridemia is strongly
      associated with a constellation of potentially atherogenic and thrombogenic
      lipoprotein changes, including a) increase in the plasma concentration of
      intestinally derived chylomicrons and their remnants; b) increase in the level of
      hepatic very low density lipoproteins and their remnants; c) decrease in level of
      high density lipoprotein (HDL) cholesterol because of increase in cholesteryl
      transfer from HDL to postprandial triglyceride-rich lipoproteins (TRL); d)
      decrease in low density lipoprotein (LDL) size, associated with increased
      susceptibility of LDL to oxidation; and e) increase in the association of
      lipoprotein (a) with TRL. Postprandial TRL are potentially thrombogenic because
      they are associated with increased activated factor VII activity (a procoagulant
      effect) and increased levels of plasminogen activator inhibitor-1 (an
      antifibrinolytic effect). Experimental results and clinical trial data suggest
      that plasma accumulation of remnant lipoproteins (in the fed or fasted state) is
      not just an associated feature of an atherogenic lipoprotein profile but that TRL
      remnants themselves contribute to the pathogenesis of atherosclerosis. Diet
      and/or drug treatments that lower the level of TRL in the fasted state also tend
      to have a beneficial effect on postprandial lipoprotein levels. Thus, aerobic
      exercise, weight reduction and triglyceride-lowering medications all reduce
      postprandial triglyceridemia and have the potential to reduce the level of
      atherogenic remnant lipoproteins.

PMID- 9627539
TI  - Advances in drug treatment of dyslipidemia: focus on atorvastatin.
AB  - The focus of lipid-lowering therapy with drugs is prevention of complications of
      atherosclerosis. Landmark clinical trials have demonstrated that lowering low
      density lipoprotein cholesterol (LDL-C) may not only reduce coronary artery
      disease (CAD) risk but also may slow the progression and even induce regression
      of atherosclerosis in the coronary arteries. In addition, much attention has been
      given in recent years to the importance of triglyceride-rich lipoprotein (TRL) as
      a CAD risk factor, and the benefit of reducing plasma triglyceride levels and
      raising high density lipoprotein cholesterol (HDL-C) levels to prevent the
      recurrence of coronary events. Lipid-lowering drugs should be used within the
      framework of a systematic approach to treatment. Consideration must be given to
      the lipoprotein abnormality, the severity of disease, the role of combination
      therapy, and the spectrum of action of the drug and its pleiotropic effects (ie,
      effects beyond the expected action on lipoproteins). Five major agents have been
      used for the treatment of dyslipidemias. Three (resins, probucol and statins)
      target LDL-C, and two (fibrates and niacin) target primarily TRL and HDL-C.
      Fibrates and statins are the drugs of choice. Fibrates correct many abnormalities
      of lipoprotein metabolism in addition to having beneficial pleiotropic effects
      such as reducing fibrinogen and plasma viscosity. They inhibit the transcription
      of apolipoprotein (apo) CIII and enhance that of apoAI and lipoprotein lipase.
      Statins are safe and potent drugs for reducing LDL-C levels, and their efficacy
      in primary and secondary prevention of CAD has been amply demonstrated. They
      share a modes effect of raising HDL-C levels. Their pleiotropic effects, which
      include improvement of endothelial dysfunction, are numerous and may contribute
      to their spectacular beneficial effect of reducing CAD risk. They have effects
      that are complementary to those of fibrates, but the two drugs should be combined
      with caution because of the danger of myopathy. Atorvastatin is a major addition
      to this class of drugs because of its high efficacy and large spectrum of action.
      It lowers LDL-C levels effectively, not only in patients with severe forms of
      hypercholesterolemia but also in those with homozygous familial
      hypercholesterolemia. The effect of atorvastatin on LDL-C may be further enhanced
      by combining it with a resin. The ability of atorvastatin to lower triglyceride
      levels as well as LDL-C levels indicates that combined hyperlipidemia, a
      condition that, in the past, was best controlled with combination therapy, can
      now be treated with a single drug. It is also effective in patients with isolated
      hypertriglyceridemia and, although less potent than fenofibrate at reducing TRL
      and increasing HDL-C, it has a greater impact on the atherogenic risk ratios such
      as LDL-C:HDL-C. The profile of its pleiotropic effects is promising.

PMID- 9627540
TI  - Assessing outcomes of surgical procedures.

PMID- 9627541
TI  - Neoplastic pulmonary embolism.

PMID- 9627542
TI  - Radiology for the surgeon. Case 21. Enteroclysis--adhesion causing partial small
      bowel obstruction.

PMID- 9627544
TI  - General surgery in the year 2000: looking to the future.
AB  - The goal of the 1997 Canadian Association of General Surgeons presidential
      address was to predict the future for general surgery in Canada in an optimistic
      fashion. However, on the basis of its current status, the vision for general
      surgery also includes the reality of the problems that the specialty will face.
      General surgeons must become advocates so as to help resolve these problems for
      the community and for their patients.

PMID- 9627543
TI  - Patient characteristics that affect the outcome of total hip arthroplasty: a
      review.
AB  - OBJECTIVE: To review the literature regarding patient factors pertinent to the
      outcome of total hip arthroplasty (THA). DATA SOURCE: MEDLINE from 1966 onward
      (key words "hip prosthesis" and "treatment outcome") and literature previously
      known to the authors and cited in papers from all sources. STUDY SELECTION: All
      identified studies were included provided the methodology permitted assessment of
      the effect of patient factors and a clear outcome was defined (either prosthesis
      survival or specific functional outcomes). DATA EXTRACTION: The patient factors,
      methods and outcomes described in each paper were summarized on a data extraction
      form. DATA SYNTHESIS: All data were reviewed by one author. This process was
      repeated by a second author, and the findings were reviewed by the remaining 2
      authors to verify the findings. The best functional outcomes and prosthesis
      survival rates were reported among patients who were between 45 and 75 years of
      age, weighed less than 70 kg, had strong social support, had a higher educational
      level, had better preoperative functional status and had no comorbid disease.
      CONCLUSION: Important research remains to be done to examine the magnitude and
      interaction of patient factors on the the outcome of THA.

PMID- 9627545
TI  - Should patients be screened for asymptomatic carotid artery stenosis?
AB  - OBJECTIVE: To evaluate, against published guidelines, the potential role of
      screening to reduce the risk of stroke and death from asymptomatic carotid artery
      stenosis (ACAS). DATA SOURCES: Papers selected for review were identified through
      a GRATEFUL MED literature search, from personal files and from references
      documented in identified papers. STUDY SELECTION: Population studies concerning
      disease prevalence, natural history studies related to risk of stroke, randomized
      controlled trials related to carotid endarterectomy and natural history studies
      related to the risk of developing ACAS were considered for review. DATA
      EXTRACTION: An estimate was made of the potential for stroke resulting from ACAS
      in the general population. This was evaluated against the positive predictive
      value of duplex scanning, and the number of patients needing to be screened to
      prevent a stroke was estimated. DATA SYNTHESIS: The prevalence of ACAS in the
      general population was estimated to range from 2% to 8% for ACAS 50% or greater
      and to range form 1% to 2% for ACAS 80% or greater. The yearly risk of stroke or
      death from undetected ACAS was estimated to be 0.16% for ACAS 50% or greater and
      0.06% for ACAS 80% or greater. The estimated number of patients needing to be
      screened to prevent 1 stroke would range from 850 to 1700 (and potentially as
      high as 8500). CONCLUSIONS: General screening for ACAs to prevent stroke and
      death cannot be recommended when evaluated against guidelines. The decision to
      screen individual patients will require judgement, continued evaluation and
      surveillance of the results of such screening by the treating physician.

PMID- 9627546
TI  - Current indications for carotid endarterectomy.
AB  - Randomized, prospective trials examining the effectiveness of carotid
      endarterectomy have given distinct information into the mechanisms and prevention
      of embolic strokes. The North American Symptomatic Carotid Endarterectomy Trial
      (NASCET) and the Asymptomatic Carotid Atherosclerosis Study (ACAS) have
      demonstrated the benefits of carotid endarterectomy for patients who meet the
      precise selection criteria and are treated according to established study
      protocols. The existing challenge to clinicians lies in the application of trial
      results to the individual patient.

PMID- 9627547
TI  - Appropriate imaging before carotid endarterectomy.
AB  - The question of which imaging method to use before performing carotid
      endarterectomy is a common and practical issue confronted by vascular surgeons.
      The imaging modalities of duplex ultrasonography, angiography, computed
      tomography (CT) and magnetic resonance angiography (MRA) have all been used in
      the preoperative assessment of the patient scheduled for carotid endarterectomy.
      This article focuses on these 4 modalities, with particular emphasis on the
      advantages and disadvantages of duplex ultrasonography versus angiography. The
      emergence of duplex ultrasonography as the sole preoperative imaging test has
      generated controversy among vascular surgeons and other specialists who deal with
      patients with carotid artery disease. Angiography, which has been the "gold
      standard" imaging test in the past and has been the reference standard in the
      large, randomized controlled trials, imposes a small but definite risk of stroke
      and death. Duplex ultrasonography can be used as the sole preoperative imaging
      test on a selective basis, provided that there is institutional validation and
      ongoing quality assurance. Although MRA is not widely available, the combination
      of MRA and duplex ultrasonography can provide similar diagnostic accuracy to
      angiography in some institutions. Routine CT appears to be unnecessary but is
      useful in certain circumstances.

PMID- 9627548
TI  - Improving perioperative management of carotid endarterectomy.
AB  - Multiple components of the perioperative course of patients who undergo carotid
      endarterectomy must be tightly controlled in order to maintain an acceptably low
      complication rate. These factors include appropriate patient selection, routine
      assessment of cardiac risk factors, precise control of blood pressure
      intraoperatively and postoperatively, meticulous surgical technique and reliable
      monitoring for intraoperative cerebral ischemia. This discussion focuses on the
      vascular practice patterns at the University of Chicago and emphasizes
      intraoperative management and the safe utilization of intraluminal shunts.

PMID- 9627549
TI  - Mechanical integrity of subchondral bone in osteochondral autografts and
      allografts.
AB  - OBJECTIVE: To assess the influence of osteochondral graft preservation techniques
      on post-transplant biomechanics of graft and host subchondral bone in the knee
      joint. DESIGN: An experimental animal model (sheep), specifically the weight
      bearing articular surface of the medial femoral condyle of the knee joints.
      INTERVENTION: Each sheep received, in the ipsilateral knee, an allograft that was
      (a) frozen without dimethyl sulfoxide (DMSO), (b) snap-frozen in liquid nitrogen
      or (c) frozen with DMSO. The contralateral knee received an autograft that was
      (a) snap-frozen, (b) treated with DMSO or (c) left untreated (fresh). MAIN
      OUTCOME MEASURES: Mechanical and material properties of bone, including maximal
      compression stress, modulus of elasticity and bone cores (from the graft centre
      and surrounding host bone). RESULTS: No significant differences were found in the
      mechanical properties of the subchondral bone under the graft, but there were
      significant changes in surrounding bone. Bone surrounding the grafts that were
      snap-frozen or frozen without DMSO was significantly stronger than the normal
      control bone. However, bone surrounding fresh autografts and cryoprotected
      allografts was not significantly different from normal control bone. CONCLUSIONS;
      The changes in the mechanical behaviour of the host bone may be associated with
      graft cell viability. The great stiffness of the subchondral host bone may have
      consequences for long-term graft integrity and for the development of
      degenerative osteoarthritis.

PMID- 9627550
TI  - Bilateral femoral component breakage in total hip replacement: a case report.
AB  - Breakage of the femoral component of a total hip replacement prosthesis is an
      uncommon occurrence with modern prostheses. The authors report what appears to be
      the only case of bilateral prosthetic fracture. A 65-year-old man, who was
      physically active, suffered bilateral femoral stem fractures 3 and 5 years after
      total hip replacement. The bilateral cemented hip replacements remained
      asymptomatic until catastrophic failure of the femoral component occurred. Both
      prostheses were titanium (Biomet; Warsaw, Ind.) with chrome cobalt modular
      femoral heads. The authors stress the importance of maintaining an adequate
      cement mantle in Gruen zones 1 and 7 because failure to do so may result in
      micromotion and subsequent stem fracture.

PMID- 9627551
TI  - Ventriculoperitoneal shunt knot: a rare cause of bowel obstruction and ischemia.
AB  - Small-bowel obstruction caused by knotting of a peritoneal shunt catheter is an
      extremely rare and severe complication of a ventriculoperitoneal (VP) shunt. In
      the 1-week-old female infant reported here who had a VP shunt, inability to
      remove the peritoneal catheter was followed by small-bowel obstruction and
      necrosis due to intestinal strangulation in a tight loop of the catheter. An
      uncomplicated primary resection of the necrotic segment was followed by placement
      of a temporary ventriculoatrial shunt. The authors suggest that when withdrawal
      of the peritoneal part of a VP shunt meets with resistance, an intraoperative
      radiograph should be obtained to assess the position of the remaining catheter.
      If knotting is observed, an attempt to straighten the catheter with a guide wire
      is worthwhile. Should this fail, immediate laparoscopy or laparotomy is
      indicated.

PMID- 9627552
TI  - Surgical management of acquired rectourethral fistula, emphasizing the posterior
      approach.
AB  - Rectourethral fistula is an uncommon surgical entity having a variety of
      congenital and acquired causes. Although several surgical approaches have been
      proposed in the literature, successful repair is often difficult. The 2 patients
      described had rectourethral fistulas after radical prostatectomy. One patient
      failed previous transabdominal and perineal repairs. The authors propose a 3-step
      approach to management of acquired rectourethral fistulas. A diverting transverse
      colostomy with insertion of a suprapubic or indwelling silicone rubber Foley
      catheter for 3 to 6 months will allow for a decrease in the inflammatory response
      surrounding the involved area and possible spontaneous closure. If spontaneous
      closure does not occur within this time, the fistula should be closed operatively
      through a posterior approach (modified York-Mason procedure). This approach
      provides excellent exposure and allows the suture lines to be offset, which in
      turn allows for better healing, present a minimal risk of impotence or
      incontinence and allows for complete separation of urinary and fecal streams. The
      third step involves closure of the colostomy followed by removal of the Foley or
      suprapubic catheter if there is no recurrence. Timing of this step is crucial and
      should be individualized according to the postoperative course.

PMID- 9627553
TI  - Total joint replacement in multiplex congenita contractures: a case report.
AB  - A 34-year-old man with multiplex congenita contractures underwent replacement of
      2 hips and 1 knee. Even though a good range of movement was achieved at surgery
      and intensive physiotherapy, his joints returned to their preoperative status
      within 2 years. This outcome suggests that total joint replacement has little to
      offer the patient with multiplex congenita contractures who has immobile joints.

PMID- 9627554
TI  - Duplication cyst of the antrum: a case report.
AB  - Gastrointestinal duplication is a rare congenital anomaly. Although it usually
      presents within the first few years of life, it may appear much later as
      described in this report of a 19-year-old man who had symptoms of gastric outlet
      obstruction. He was found to have a noncommunicating antral duplication cyst. The
      cyst was managed by antrectomy with excision of the cyst and several centimetres
      of duodenum. Microscopically the duplication cyst contained a mucosa, submucosa
      and muscularis. There was no evidence of ulceration or malignant cells. His
      recovery was smooth. The etiology, presentation and management of antral
      duplication cysts causing gastric outlet obstruction are discussed.

PMID- 9627555
TI  - Choosing between SSRIs and TCAs.

PMID- 9627556
TI  - Antibacterial activity of fluorescein.

PMID- 9627557
TI  - The BSE advantage.

PMID- 9627558
TI  - The imaging of incidentalomas.

PMID- 9627559
TI  - The delay to thrombolysis: an analysis of hospital and patient characteristics.
      Quebec Acute Coronary Care Working Group.
AB  - OBJECTIVE: To describe the various components of the delay to thrombolytic
      treatment for patients with acute myocardial infarction (MI) and to identify the
      hospital and patient characteristics related to these delays. DESIGN: Cohort
      analysis from a hospital registry of patients receiving thrombolytic treatment.
      SETTING: Forty acute care hospitals in Quebec. SUBJECTS: All 1357 patients who
      received thrombolysis between January 1995 and May 1996. MAIN OUTCOME MEASURES:
      Time from onset of symptoms to arrival at hospital and the various components of
      the in-hospital delay. RESULTS: The median delay before presentation to hospital
      was 98 (interquartile range [IR] 56 to 180) minutes and was longer for women (p <
      0.001), patients over 65 years of age (p < 0.001) and patients with diabetes
      mellitus (p < 0.01). The median time from arrival at hospital to thrombolysis was
      59 (IR 41 to 89) minutes, the medical decision-making component taking a median
      of 12 (IR 4 to 27) minutes. Women (p < 0.005), older patients (p < 0.001) and
      patients with a past history of MI (p < 0.001) had increased in-hospital delays
      to thrombolysis. Delays were longer in community hospitals (p < 0.05) and low
      volume centres (p < 0.01) and when a cardiologist made the decision to administer
      thrombolysis (p < 0.001). Multivariate analysis showed that increased age (odds
      ratio 1.5, 95% confidence interval 1.3 to 1.7, p < 0.001) and having the medical
      decision made by a cardiologist (odds ratio 1.8, 95% confidence interval 1.6 to
      2.0, p < 0.001) were independently associated with an increased risk of being in
      the upper median of in-hospital delays. CONCLUSIONS: Despite certain
      improvements, there remain substantial delays between symptom onset and the
      administration of thrombolysis for patients with acute MI. A large part of the
      delay is due to the hesitation of patients (particularly women, older patients
      and patients with diabetes) to seek medical attention. Although the median time
      for medical decision-making appears reasonable, care must be taken to ensure that
      all patient groups receive timely evaluation and therapy. The delay associated
      with having the treatment decision made by a cardiologist probably represents a
      marker for more difficult, complex cases. Methods should be developed to permit
      specialty consultation, if needed, while minimizing treatment delays. Community
      and low-volume hospitals may require special attention.

PMID- 9627560
TI  - Common bile duct injury during laparoscopic cholecystectomy in Ontario: does ICD
      9 coding indicate true incidence?
AB  - BACKGROUND: Recent reports in the scientific and lay press have suggested that
      bile duct injuries during laparoscopic cholecystectomy are common in Ontario. The
      reports were based on administrative data collected by hospital medical records
      departments and the Canadian Institute for Health Information (CIHI). The current
      study involved a direct inspection of hospital records to determine if the CIHI
      data accurately captured the rate of clinically significant bile duct
      complications. METHODS: For the period 1991 to 1995, records of bile duct
      injuries after laparoscopic cholecystectomy were independently evaluated to
      clarify the clinical significance of the complications. Of 21 Ontario hospitals
      for which data on complications had been reported in the media, 18 provided
      detailed information on all patients reported to have suffered bile duct
      complications classified by the hospital as "major". In addition, each
      institution provided information on a random sample of one-sixth of the patients
      who had suffered complications classified as "minor". The reviewer then examined
      each relevant hospital chart to assess the grade and significance of the reported
      complications. RESULTS: All 24 bile duct injuries classified by the hospitals as
      "major" were confirmed as major (clinically relevant) injuries. Of the 80 bile
      duct complications classified by the hospitals as "minor", 76 (95%) were
      irrelevant to patient outcome. The discrepancy between data collected and
      reported frequency of injury lies in the use of nonspecific coding methods.
      INTERPRETATION: The rate of significant bile duct injuries cannot be inferred
      from nonspecific codes taken from the International Classification of Diseases,
      ninth revision, and presented in hospital discharge records. Therefore, such data
      must be interpreted with extreme caution.

PMID- 9627561
TI  - Administrative databases: fact or fiction?

PMID- 9627562
TI  - Cardiopulmonary resuscitation for patients in a persistent vegetative state:
      futile or acceptable?

PMID- 9627563
TI  - Guidelines for antiretroviral therapy for HIV infection. Canadian HIV Trials
      Network Antiretroviral Working Group.
AB  - OBJECTIVE: To develop guidelines for health care providers and their HIV-positive
      patients on the clinical use of antiretroviral agents for HIV infection. OPTIONS:
      Recommendations published in 1996 by an international panel. OUTCOMES:
      Improvement in clinical outcomes or in surrogate markers of disease activity.
      EVIDENCE AND VALUES: The Canadian HIV Trials Network held a workshop on Oct. 19
      20, 1996, to develop Canadian guidelines that incorporate information from recent
      basic and clinical research. RECOMMENDATIONS: Recommendations for the use of
      antiretroviral drugs in HIV infection are provided for initial therapy,
      continuing therapy, primary infection, vertical transmission, pediatric therapy
      and postexposure prophylaxis. VALIDATION: The guidelines are based on consensus
      of the participants attending the workshop: Canadian investigators, clinicians
      and invited representatives from the community, government and the pharmaceutical
      industry. They are subject to review and updating as new information on clinical
      benefits is published. SPONSORS: The workshop was organized by the National
      Centre of the Canadian HIV Trials Network. Unrestricted educational grants were
      provided by 8 pharmaceutical companies. Additional support was provided from the
      National AIDS Strategy of Health Canada.

PMID- 9627565
TI  - Suicide and life: the ultimate juxtaposition.

PMID- 9627564
TI  - Insulin lispro (Humalog), the first marketed insulin analogue: indications,
      contraindications and need for further study.
AB  - OBJECTIVE: To review the available literature on the new insulin analogue insulin
      lispro and provide information on its efficacy, indications for use and
      contraindications. DATA SOURCES: MEDLINE searches were made for articles
      published from 1966 to 1996 using the indexing term "lispro", "Humalog" and
      "insulin analogs". STUDY SELECTION: About 30 studies and review articles were
      selected based on their relevance to the stated objective. These were critically
      appraised for the purpose of writing the review article so that it would be
      relevant to general practitioners, internists and nurse educators. DATA
      SYNTHESIS: The therapeutic challenge when treating diabetic patients is to bring
      the blood glucose level into as normal a range as possible, with minimal
      hypoglycemia and hyperinsulinemia. Insulin lispro has a much faster, higher and
      shorter-lasting peak serum insulin level than regular human insulin, thus
      mimicking physiologic secretion of insulin more closely. As a result, there is
      improvement in postprandial blood glucose levels and decreased episodes of
      hypoglycemia, with no change in the hemoglobin A1c (HgbA1c) level. The ability to
      inject insulin lispro immediately before the meal allows greater flexibility of
      lifestyle. Compared with regular insulin, insulin lispro is associated with a
      lower risk of hypoglycemia with exercise several hours after a meal. It is
      therefore most useful for the motivated, compliant diabetic patient who would
      like to achieve a better hypoglycemia-HgbA1c ratio as well as for patients
      desiring further flexibility with premeal insulin injections. Use of insulin
      lispro has been shown to improve HgbA1c levels in patients using insulin pumps.
      It is well tolerated, and therapy is often continued after studies are completed.
      Further study is needed to establish optimal basal regimens.

PMID- 9627566
TI  - Rubella outbreaks on cruise ships.

PMID- 9627567
TI  - Quebec's ice storm '98: "all cards wild, all rules broken" in Quebec's shell
      shocked hospitals.
AB  - The remarkable ice storm that brought life to a standstill in most of Eastern
      Ontario and Quebec in January had a huge impact on medical services. Hospitals
      that lost power found themselves serving as shelters not only for patients but
      also for staff members and nearby residents. Doctors' offices were forced to
      close and a large number of operations were cancelled. The 2 articles that follow
      detail the huge impact the "ice storm of the century" had on health care.

PMID- 9627568
TI  - 7:10 am, Nov. 8, 1994. Interview by Anne Mullens.
AB  - Dr. Garson Romalis, a Vancouver physician who performed abortions, was shot and
      severely wounded by an unknown assailant 3 years ago. In this article he tells
      Anne Mullens about the incident and its aftermath. The shooting, which has since
      been linked with the attempted murder of 2 other abortion providers, has not
      changed Romalis' views on the importance of the procedure. Today his major
      concern is that young physicians will be too frightened to provide an essential
      and legal service. He is working to convince medical students of the need to
      continue providing abortions.

PMID- 9627569
TI  - [Research activities of medical students in Germany using as an example the
      Wurzburg University Clinic].
AB  - BACKGROUND AND OBJECTIVE: Many medical students in Germany take part in research
      at their university, as part of their work on a doctoral dissertation. There are
      alternatives to this model in other countries. To have a basis for comparison,
      the research activities of medical students at the University of Wurzburg were
      analysed. METHOD: A questionnaire was sent to all members of the teaching staff
      of the medical faculty of the University Wurzburg (n = 238). It contained 20
      questions about the number of students whose research had been supervised,
      duration of the research, number of uncompleted research studies, cost of
      materials, resulting publications and estimate of value of the research done.
      Among those questioned were two groups of professors (50 and 66 respectively, 122
      senior lecturers or titular professors). RESULTS: 106 faculty members answered
      the questionnaire sent to them (45%), 66 working clinically, 26 in a clinic
      related institute and 14 in basic research. The students' research usually
      started in their 4th year and on average took up 216 full-time days. The average
      training period had lasted for 3 months, 10% of student broke off their research,
      and each faculty member supervised a mean of 4.5 students. Nonexperimental work
      (48.3%) cost on average DM 2300, experimental work (51.7%) DM 15,000. Generally
      two publications resulted and one or two posters/oral communications per student.
      Two-thirds of the faculty members thought that research undertaken by medical
      students was important for maintaining a qualitatively and quantitatively high
      publication level at a university clinic. CONCLUSION: Work on a doctoral
      dissertation not only promotes scientific thinking of the future doctor but also
      contributes towards maintaining scientific standards.

PMID- 9627570
TI  - [Duplication cyst of the stomach antrum as the cause of an acute gastric emptying
      disorder in an adult].
AB  - HISTORY AND CLINICAL FINDINGS: A 35-year old woman without previous history of
      gastrointestinal complaints developed increasing upper abdominal pain with nausea
      and postprandial vomiting over 2 days during which she had been unable to take
      any food. She had no fever; her general physical condition was slightly reduced.
      While her abdomen felt soft on palpation, she had epigastric pain on pressure but
      no resistance to palpation. INVESTIGATIONS: Blood picture and routine laboratory
      tests were unremarkable. Plain film of the abdomen demonstrated marked gastric
      retention. Abdominal ultrasound showed an invagination in the gastric antrum
      suggesting a layering phenomenon. Gastroscopy revealed a submucosal tumour-like
      lesion with central ulceration which obstructed gastric exit. TREATMENT AND
      COURSE: After conclusion of the diagnostic tests on the first hospital day
      partial gastric resection (Billroth I) was performed as, in the absence of any
      surrounding reaction, a leiomyoma had been suspected. The further course was
      without complication and she was discharged on the 13th hospital day. The
      surgical specimen revealed a duplication cyst of the gastric antrum. CONCLUSION:
      (Endo)sonography, computed tomography and endoscopy make it possible to diagnose
      duplication cyst, as long as it is included in the differential diagnosis of
      acute abdomen in an adult. Emergency resection of the cyst is indicated because
      of the acute nature of the symptoms. But even in less urgent cases or as an
      incidental finding it is the treatment of choice.

PMID- 9627571
TI  - [Ocular toxocariasis in Austria].
AB  - HISTORY AND CLINICAL FINDINGS: Two women (aged 21 and 44 years) were referred
      because of a suspect retinal lesion. An ophthalmological examination in both
      revealed prominent retinal granulomatous foci, probably ocular toxocariasis. Both
      women were otherwise well; both reported close contact with dogs. INVESTIGATIONS:
      Among a full array of laboratory tests the only major pathologic findings were
      high antibody titres against Toxocara canis (patient 1: 70 antibody units [AU];
      patient 2: > 100 AU), specific antibodies in the ELISA and Western blot tests
      confirming the diagnosis of T. canis infection. DIAGNOSIS, TREATMENT AND COURSE:
      Both patients were treated with prednisolone (initially 75 mg/d, gradually
      decreasing over 4 months) and albendazole (2 x 800 mg/d for 6 days), with
      complete healing of the chorioretinal foci. CONCLUSION: General physicians as
      well as ophthalmologists should more often include Toxocara canis infection in
      the differential diagnosis, because the larvae, in their migration through the
      body, can infest various organs where they can cause inflammatory or allergic
      reactions.

PMID- 9627572
TI  - [Medical treatment of intestinal hemorrhage in portal hypertension].

PMID- 9627573
TI  - [Hepatitis C virus-associated cryoglobulinemic vasculitis. Physiopathology,
      diagnosis and therapy].

PMID- 9627574
TI  - [Learning without end. The medical guideline--an instrument for further education
      in the future?].

PMID- 9627575
TI  - [Therapy of obesity].

PMID- 9627576
TI  - SIDS and disorders of fatty acid oxidation: where do we go from here?

PMID- 9627577
TI  - Prophylaxis for hemophilia: state of the art or state of confusion?

PMID- 9627578
TI  - Haldane was right: de novo mutations in androgen insensitivity syndrome.

PMID- 9627579
TI  - Current perspectives on pyridoxine-dependent seizures.

PMID- 9627580
TI  - Retrospective biochemical screening of fatty acid oxidation disorders in
      postmortem livers of 418 cases of sudden death in the first year of life.
AB  - OBJECTIVE: Fatty acid oxidation (FAO) disorders are frequently reported as the
      cause of sudden and unexpected death, but their postmortem recognition remains
      difficult. We have devised a biochemical protocol in which informative findings
      in liver tissue are microvesicular steatosis, elevated concentrations of C8-C16
      fatty acids, glucose depletion, and low carnitine concentration. STUDY DESIGN: We
      analyzed 27 cases representing five FAO disorders and compared the results with
      those obtained in a retrospective blinded analysis of 418 cases of sudden infant
      death (313 SIDS, 45 infections, and 34 accidents and abuse). RESULTS: All cases
      of accidents and abuse correctly tested negative. Among the others, 25 (6%)
      showed at least two abnormal findings. Of these, 14 closely matched the
      biochemical profiles seen in specific FAO disorders. These included 2 cases with
      medium-chain acyl-CoA dehydrogenase deficiency, 4 cases consistent with glutaric
      acidemia type 2, 4 cases with either very long-chain acylcoenzyme A dehydrogenase
      deficiency or long-chain 3-hydroxy-acyl-coenzyme A dehydrogenase deficiency, and
      4 cases predicted to be affected with carnitine uptake defect. CONCLUSION: The
      results of this study support the view that approximately 5% of all cases of
      sudden infant death are likely caused by an FAO disorder.

PMID- 9627581
TI  - Implantable venous access devices in children with hemophilia: a report of low
      infection rates.
AB  - OBJECTIVE: The objective of this study was to define the efficacy and
      complications of implantable venous access devices (IVADs) in children with
      hemophilia. STUDY DESIGN: Records were reviewed on all patients with congenital
      blood coagulation disorders monitored at two children's hospitals in whom one or
      more central venous catheters had been placed. RESULTS: Since 1989 external and
      implantable central venous catheters have been inserted to enhance venous access
      for regular factor concentrate infusion in 45 patients with hemophilia ranging in
      age from 8 months to 19.5 years (median 7.4 years); 37 patients had factor VIII
      deficiency and 8 factor IX deficiency. Hemorrhagic complications of catheter
      placement were infrequent and minor. In the 41 patients having one or more IVADs
      in place for a median of 31 months, only six episodes of bacteremia occurred in 5
      patients during 44,070 days of follow-up. The overall rate of bacteremia
      complicating IVADs in these patients was 0.14 episodes per 1000 catheter days.
      Other catheter-related complications were uncommon. Catheters are still in place
      in 33 patients for a median of 32 months. CONCLUSION: The low risk of infection
      and other complications associated with the use of IVADs makes the use of these
      devices attractive in the treatment of patients with hemophilia who require
      frequent venous access for factor concentrate infusions.

PMID- 9627582
TI  - Inherited and de novo androgen receptor gene mutations: investigation of single
      case families.
AB  - OBJECTIVE: The objective of this study was to assess somatic and inherited
      androgen receptor gene mutations in families with only one affected individual.
      METHODS: Molecular genetic analysis of the androgen receptor gene in DNA derived
      from blood leukocytes from 30 families with single-strand conformation analysis,
      direct sequencing, and restriction fragment analysis was performed. RESULTS: In
      22 families the mothers and all investigated grandmothers were heterozygous
      carriers. However, within the sisters and aunts, both heterozygous carriers and
      noncarriers were present. In eight families a de novo mutation was characterized.
      In three of these patients indication for somatic mosaicism was found.
      CONCLUSIONS: De novo mutations occur at a high rate within the androgen receptor
      gene (8 of 30 = 26.7%); a high proportion (3 of 8) arise after the zygote stage.
      Thus only direct analysis of the underlying mutation of the androgen receptor
      gene in the proband and his or her family can provide the basis for genetic
      counseling.

PMID- 9627583
TI  - Long-term glycemic control influences the onset of limited joint mobility in type
      1 diabetes.
AB  - BACKGROUND: Limited joint mobility (LJM) in childhood insulin-dependent (type 1)
      diabetes is associated with a substantially increased risk of microvascular
      complications. Cross-sectional studies have not demonstrated a relationship
      between LJM and metabolic control. This study was designed to determine whether
      glycemic control, as measured by glycohemoglobin (hgbA1C) levels from the onset
      of diabetes, is associated with the occurrence of LJM. METHOD: Probands (n = 18)
      had hgbA1C values and recorded observation of joint function from soon after
      onset of their diabetes. Controls (n = 40) were matched to probands for gender
      and age at diagnosis and had follow-up beyond the age at which the proband was
      found to have LJM. RESULTS: The odds ratio for occurrence of LJM for the mean
      hgbA1C from diabetes onset was 1.46, 95% confidence limits 1.07 to 2.00. Thus,
      for every unit increase in average hgbA1C, there was approximately a 46% increase
      in the risk of LJM. When hgbA1C was dichotomized, the OR for hgbA1C of more than
      8% was 2.55, and the OR was 4.54 if the hgbA1C was greater than 12%. Age at
      diagnosis and duration of diabetes were not independent prognostic factors for
      LJM. CONCLUSION: Glycemic control from onset of diabetes is strongly associated
      with occurrence of LJM.

PMID- 9627584
TI  - Exogenous insulin reduces proteolysis and protein synthesis in extremely low
      birth weight infants.
AB  - OBJECTIVE: To determine the effect of a continuous insulin infusion on protein
      and glucose metabolism in extremely low birth weight (ELBW) infants. STUDY
      DESIGN: We measured the rate of appearance (Ra) of the essential amino acids
      leucine and phenylalanine (reflecting proteolysis), utilization of phenylalanine
      for protein synthesis, and glucose Ra using stable isotope tracers during a basal
      infusion of glucose (6 mg/kg/min) and in response to a continuous infusion of
      insulin (0.05 U/kg/hr) by means of the euglycemic hyperinsulinemic clamp
      technique. Four clinically stable, euglycemic ELBW infants (26 +/- 0 weeks'
      gestation, 894 +/- 44 gm birth weight, 2.8 +/- 0.8 days of age) were studied.
      RESULTS: In response to a greater than tenfold increase in insulin concentration
      (from 7 +/- 2 to 79 +/- 13 microU/ml), there was a 20% decrease in leucine Ra
      (Basal: 272 +/- 27 mumol/kg/hr; Insulin: 226 +/- 29 mumol/kg/hr; p < 0.01) and in
      phenylalanine Ra (Basal: 91 +/- 5 mumol/kg/hr; Insulin: 72 +/- 2 mumol/kg/hr; p <
      0.05). Use of phenylalanine for protein synthesis also decreased by a similar
      magnitude (Basal: 77 +/- 4 mumol/kg/hr; Insulin: 62 +/- 1 mumol/kg/hr; p < 0.05).
      Glucose utilization doubled (from 8 +/- 0.9 to 15.7 +/- 1.1 mg/kg/min; p =
      0.0003) and plasma lactate concentrations tripled (from 2.1 +/- 0.5 to 5.7 +/-
      1.0 mmol/L; p < 0.05) during the insulin infusion. CONCLUSIONS: During an
      infusion of glucose alone, pharmacologic concentrations of insulin in ELBW
      infants produced no net protein anabolic effect. Furthermore, euglycemic
      hyperinsulinemia was accompanied by development of significant metabolic
      acidosis.

PMID- 9627585
TI  - Physiological, hormonal, and behavioral responses to a single fentanyl dose in
      intubated and ventilated preterm neonates.
AB  - OBJECTIVE: To study the responses of ventilated preterm neonates to a single dose
      of opioid. STUDY DESIGN: In a randomized, double-blind, controlled trial, 22
      mechanically ventilated preterm infants (< or = 32 weeks) were observed before
      medication and at 30 and 60 minutes after administration of fentanyl (3
      micrograms/kg) or placebo. Heart rate, blood pressure, arterial blood gases,
      ventilator settings, and behavioral measures (Neonatal Facial Coding System and
      Modified Postoperative Comfort Score) were recorded during each period. Blood
      cortisol, growth hormone, glucose, and lactate were measured before and at 60
      minutes after analgesia. Behavioral measures were assessed at the bedside and
      from video films recorded during each observation period. RESULTS: Patients
      presented high basal levels of cortisol, growth hormone, and lactate. Behavioral
      scales indicated the presence of pain before any medication. In the fentanyl
      group, the maximum and minimum heart rate decreased and growth hormone level
      increased after analgesia. At the video analysis of behavioral measures,
      postoperative comfort score increased and neonatal facial coding system score
      decreased in the fentanyl group. CONCLUSION: Single doses of fentanyl analgesia
      can reduce the physiologic/behavioral measures of pain and stress associated with
      mechanical ventilation in preterm infants.

PMID- 9627586
TI  - Persistence of the biphasic ventilatory response to hypoxia in preterm infants.
AB  - OBJECTIVE: To characterize postnatal maturation of the biphasic ventilatory
      response to hypoxia in order to determine whether it persists beyond the first
      weeks of life in preterm infants, and the contributions of respiratory frequency
      and tidal volume to this response. METHODS: Stable preterm infants were studied
      at two postnatal ages, 2 to 3 weeks (n = 12) and 4 to 8 weeks (n = 12), before
      hospital discharge at 35 weeks (range, 33 to 38 weeks) of postconceptional age.
      Infants were exposed to 5 minutes of 15% (or 13%) inspired oxygen; ventilation,
      oxygen saturation, end-tidal partial pressure of carbon dioxide, and heart rate
      were simultaneously recorded. RESULTS: Minute ventilation exhibited a
      characteristic biphasic response to hypoxia at both postnatal ages, regardless of
      the development of periodic breathing. At both ages there was a transient
      increase in tidal volume, which peaked at 1 minute, accompanied by a sustained
      decrease in respiratory frequency as a result of significant prolongation of
      expiratory time. CONCLUSION: The characteristic biphasic ventilatory response to
      hypoxia persists into the second month of postnatal life in preterm infants. We
      speculate that this finding is consistent with the prolonged vulnerability of
      such infants to neonatal apnea.

PMID- 9627587
TI  - Early increase in endothelin-1 in tracheal aspirates of preterm infants:
      correlation with bronchopulmonary dysplasia.
AB  - OBJECTIVES: To determine whether endothelin-1 (ET-1) in tracheal aspirates (TA)
      is a specific marker for acute lung injury in preterm infants with respiratory
      distress syndrome (RDS) who progress to bronchopulmonary dysplasia (BPD); and to
      investigate the relationship between TA ET-1 and the proinflammatory cytokines,
      interleukin-6 (IL-6) and IL-8, as early mediators of BPD. STUDY DESIGN: We
      measured TA ET-1, IL-6, and IL-8 levels in preterm infants whose lungs were
      mechanically ventilated for RDS, categorized into two groups, BPD or non-BPD, on
      the basis of oxygen requirement at 36 weeks' postconceptional age. RESULTS: A
      total of 106 TA samples were obtained from 34 infants with gestational ages
      ranging from 24 to 28 weeks on days 1, 3, 5, and 7 of life. There was a wide
      range of ET-1 concentration. TA ET-1 levels were significantly elevated on days
      1, 3, and 7 in infants in whom BPD developed, in comparison with the non-BPD
      group (Mann-Whitney U test: p < 0.01). TA IL-8 levels were elevated on days 1, 3,
      5, and 7 in the BPD group (p < 0.01); TA IL-6 levels were elevated (p < 0.05)
      only on day 5. There was a similarity in pattern of increase of TA ET-1 and TA IL
      8 levels in the BPD group, with both being elevated in the first 24 hours of life
      and through the first week. There was no correlation between ET-1 and IL-8
      values. CONCLUSION: Early significant increase in the TA ET-1 and IL-8
      concentrations in preterm infants with acute lung injury correlates with
      subsequent progression to BPD.

PMID- 9627588
TI  - Health care use of 3-year-old low birth weight premature children: effects of
      family and neighborhood poverty.
AB  - OBJECTIVE: The objective of this study was to examine the effect of family and
      neighborhood income on health care use of young children born prematurely and of
      low birth weight (N = 619). DESIGN: A birth cohort was enrolled in a clinical
      randomized trial of early childhood educational and family services.
      SETTINGS/PARTICIPANTS: Infant Health and Development Program provided a sample of
      low birth weight premature infants stratified by clinical site, birth weight, and
      treatment group. Maternal reports of health care use, family income, and heath
      insurance were obtained at 12, 24, and 36 months of corrected age. Neighborhood
      income was based on census tract residence at birth. MAIN OUTCOME MEASURES:
      Maternal reports of hospitalizations, doctor visits, and emergency department
      visits were used; data were averaged over the child's first 3 years of life.
      RESULTS: Children from poorer families were more likely to be hospitalized and to
      have more emergency department visits than were children from more affluent
      families. Residence in poor and middle-income neighborhoods was associated with
      more emergency department visits than residence in affluent neighborhoods.
      Families in middle-income neighborhoods reported more doctor visits than families
      in poor or affluent neighborhoods. CONCLUSION: Neighborhood residence influences
      health care use by poor and nonpoor families and by insured and uninsured
      families. The use of the emergency department for low birth weight premature
      children in middle-income and poor neighborhoods is discussed.

PMID- 9627589
TI  - Dose-related efficacy of budesonide administered via a dry powder inhaler in the
      treatment of children with moderate to severe persistent asthma.
AB  - OBJECTIVE: To determine the efficacy and safety of budesonide delivered by an
      inhalation-driven dry powder inhaler (Turbuhaler) in children with moderate to
      severe persistent asthma. STUDY DESIGN: In our randomized, double-blind, placebo
      controlled, parallel-group, multicenter study, a total of 404 children with
      asthma, who were aged 6 to 18 years and who had been receiving inhaled
      glucocorticosteroid therapy, were randomly assigned to receive either 100, 200,
      or 400 micrograms of budesonide or placebo twice daily for 12 weeks. At baseline,
      mean forced expiratory volume in 1 second (FEV1) was 74.6% (range, 30.7% to
      123.3%) of the predicted normal value. RESULTS: Patients in each of the three
      budesonide treatment groups showed significant dose-related improvements in lung
      function (morning peak expiratory flow and FEV1), in asthma symptoms, and with a
      significant decrease in inhaled beta 2-agonist use in comparison with placebo.
      Improvements were evident within 2 weeks and were maintained throughout the 12
      weeks. Budesonide treatment had no significant effect on hypothalamic-pituitary
      adrenal axis function, and the incidence of reported adverse events was similar
      in all treatment groups. CONCLUSION: Budesonide administered via a dry powder
      inhaler provided dose-related improvements in lung function and clinical status
      and was well tolerated by children (6 to 18 years of age) with moderate to severe
      persistent asthma.

PMID- 9627590
TI  - Antibody responses and persistence in the two years after immunization with two
      acellular vaccines and one whole-cell vaccine against pertussis.
AB  - OBJECTIVE: To evaluate the persistence of specific antibodies induced by primary
      immunization with three doses of two three-component acellular vaccines against
      pertussis with an observed efficacy of 84%, and one whole-cell vaccine with an
      observed efficacy of 36%. STUDY DESIGN: Serum samples were collected from a
      subsample of 1572 children from the Italian double-blind, placebo-controlled,
      randomized trial of vaccines used in 15,601 children at three time points: before
      administration of the first dose of vaccine, and 1 month and approximately 15
      months after administration of the third dose. Further evaluation included pooled
      cross-sectional analysis of serum specimens associated with episodes of cough
      (which were not laboratory confirmed as pertussis infection) occurring among the
      entire population enrolled in the trial. RESULTS: With both acellular vaccines
      there was a fast and steep decrease in geometric mean antibody titers to
      pertussis toxin, filamentous hemagglutinin, and pertactin after vaccination. Mean
      titers were close to the limit of detection 15 months after primary immunization.
      The immunogenicity of the whole-cell study vaccine was poor 1 month after the
      third dose, and no antibody was detected in nearly all children 15 months after
      whole-cell vaccination. CONCLUSIONS: Although the study acellular pertussis
      vaccines induced a strong primary specific antibody response in almost all
      recipients, the duration of the response was limited. Sustained high-level
      production of antibody to the antigens tested does not account for the observed
      efficacy of acellular pertussis vaccines.

PMID- 9627591
TI  - Hepatic function as assessed by lidocaine metabolism in sickle cell disease.
AB  - OBJECTIVE: To evaluate hepatic drug metabolism, as determined by the formation of
      monoethylglycinexylidide (MEGX) after lidocaine injection and indocyanine green
      (ICG) clearance, in patients with sickle cell disease. STUDY DESIGN: A case
      control study including 19 patients with homozygous hemoglobin S, and 13 age- and
      sex-matched black control subjects. Serum MEGX concentration was measured after
      intravenous injection of 1 mg/kg (maximum 50 mg) lidocaine. ICG (0.5 mg/kg) was
      injected concomitantly and absorbance (805 nm) of serum was measured over time to
      determine its volume of distribution, serum half-life, and hepatic blood flow.
      RESULTS: MEGX formation at 15 minutes was decreased in patients with sickle cell
      disease compared with formation in the control subjects (39.9 +/- 18.0 vs 65.6 +/
      50.0 micrograms/L, respectively, p < 0.02). The volume of distribution of ICG
      was increased in patients with sickle cell disease compared with that in the
      control subjects (0.21 +/- 0.09 vs 0.11 +/- 0.03 L/kg, p < 0.01). This partly
      accounts for the decreased MEGX formation. The ICG half-life was similar in both
      groups (3.8 +/- 1.5 vs 3.1 +/- 1.0 min). Hepatic blood flow, derived from ICG
      clearance, was increased in sickle cell patients compared with that of the
      control subjects (12.2 +/- 4.5 vs 8.1 +/- 2.1 ml/kg/min, p < 0.01). CONCLUSION:
      Hepatic drug metabolism, as assessed by MEGX formation after lidocaine injection,
      is impaired in patients with sickle cell disease. This impairment may have
      clinical implications when using hepatically metabolized medications in patients
      with sickle cell disease.

PMID- 9627592
TI  - Abnormalities of the central nervous system in very young children with sickle
      cell anemia.
AB  - OBJECTIVE: To determine whether abnormalities of the CNS are present in very
      young children with sickle cell anemia. STUDY DESIGN: Thirty-nine children with
      hemoglobin SS between the ages of 7 and 48 months were examined with magnetic
      resonance imaging (MRI) and magnetic resonance angiography (MRA). No child had a
      history of clinical stroke, although 3 had a history of seizures (2 neonatal).
      Twenty-one patients underwent developmental testing with the Bayley or McCarthy
      Scales. RESULTS: The overall prevalence of CNS abnormalities in asymptomatic
      children was 4 of 36 (11%, confidence interval 3, 26%). One patient had a silent
      infarct observed on MRI and a stenotic lesion on MRA; 3 other patients had
      stenotic lesions on MRA. The 3 patients who had a history of seizures all had
      lesions consistent with infarcts on MRI. Of the asymptomatic patients who had
      psychometric testing, 1 of 18 was developmentally delayed. One of 3 with a
      history of seizures had mild developmental delay. CONCLUSIONS: Very young
      children with sickle cell anemia (and no history of clinical stroke) have
      infarction in the brain and/or stenosis of major cerebral arteries, similar to
      those reported in older children. These findings indicate a need for larger
      studies to define the incidence of CNS lesions in this age group and to determine
      the need for early therapeutic intervention to prevent CNS sequelae of sickle
      cell disease.

PMID- 9627593
TI  - Efficacy of milk versus yogurt offered as part of a mixed diet in acute
      noncholera diarrhea among malnourished children.
AB  - We compared the clinical outcome of acute diarrhea in 96 malnourished boys (aged
      4 to 47 months) receiving full-strength milk compared with yogurt offered as part
      of a mixed diet. All had weight for height less than or equal to 80% of the
      National Centre for Health Statistics median. They were randomly assigned to
      receive milk formula (MF; 67 cal/100 ml) or yogurt formula (YF; prepared from the
      same milk formula) at the rate of 120 ml/kg body weight in seven divided
      feedings. Stool-reducing substances (> 1%) were detected more frequently in the
      MF group, and the differences were significant for day 3 of the study (p = 0.04).
      However, the geometric mean (95% confidence interval) of the total stool weights
      (gm/kg) during 0 to 72 hours (MF 128.8 [103, 161.4]; YF 110.9 [87, 142.2]) was
      comparable (p = 0.37) as was the median (range) duration of diarrhea (hours) (MF
      45 [4, 183]; YF 52 [7, 173] p = 0.94). The treatment failure rates in the MF
      (8.2%) and YF (6.3%) groups were also similar (p = 0.67). The children consuming
      milk had higher median percent weight gain at the end of 72 hours of the study (p
      = 0.04) and at recovery (p = 0.02). Routine substitution of yogurt as small
      frequent feedings as an addition for semisolid food to malnourished children with
      acute diarrhea does not achieve any significant clinical benefit versus milk.

PMID- 9627594
TI  - Elimination diet in cow's milk allergy: risk for impaired growth in young
      children.
AB  - OBJECTIVE: The objective of this study was to evaluate the nutritional impact of
      therapeutic elimination diets and to identify risk factors predisposing infants
      with food allergy to poor growth. STUDY DESIGN: We studied 100 children (mean age
      7 months) with atopic dermatitis and challenge-proven cow's milk allergy and
      evaluated their growth during the symptomatic period before diagnosis and during
      the therapeutic elimination diet. RESULTS: Clinical control of symptoms was
      achieved in all patients. The mean length SD score and weight-for-length index of
      patients decreased compared with those in healthy age-matched children, p <
      0.0001 and p = 0.03, respectively. Low serum albumin was present in 6% of the
      patients, 24% had an abnormal urea concentration, and 8% had a low serum
      phospholipid docosahexaenoic acid. The delay in growth was more pronounced in a
      subgroup of patients with early onset than in those with later of symptoms (F =
      6.665, p < 0.0001). The duration of breast-feeding correlated positively with the
      sum of n-3 polyunsaturated fatty acids (r = 0.39, p = 0.001) and with the
      relative amount of docosahexaenoic acid (r = 0.36, p = 0.002). CONCLUSION: A
      delicate balance exists between the benefits and the risks of elimination diets.

PMID- 9627595
TI  - Recurrent abdominal pain: a potential precursor of irritable bowel syndrome in
      adolescents and young adults.
AB  - OBJECTIVES: To assess symptoms of irritable bowel syndrome (IBS) in patients with
      recurrent abdominal pain (RAP) 5 years after their initial evaluation, to
      identify the relation of IBS symptoms to functional disability and health service
      use, and to determine the extent to which IBS symptoms are associated with life
      stress and poor psychosocial adjustment. METHODS: Patients with RAP (n = 76) and
      control subjects (n = 49) completed a telephone interview; measures included the
      Bowel Disease Questionnaire, the Functional Disability Inventory, the Life Events
      Questionnaire, the Family Inventory of Life Events, the Center for
      Epidemiological Studies Depression Scale, the Self-Perception Profile for
      Adolescents, and the Health Resources Inventory. RESULTS: Five years after the
      initial evaluation, patients with RAP reported significantly more episodes of
      abdominal pain than did control subjects, as well as significantly higher levels
      of functional disability, school absence, and clinic visits for abdominal
      distress. Female patients with RAP were more likely than female control subjects
      to meet the Manning criteria for IBS. Among patients with RAP, higher levels of
      IBS symptoms were associated with significantly greater functional disability,
      more clinic visits, more life stress, higher levels of depression, and lower
      academic and social competence. CONCLUSION: Female patients with a history of RAP
      may be at increased risk of IBS during adolescence and young adulthood. Among
      adolescents and young adults with a history of RAP, IBS symptoms are likely to be
      associated with high levels of disability and health service use.

PMID- 9627596
TI  - Diagnosis and management of stenotic aorto-arteriopathy in childhood.
AB  - Stenotic aorto-arteriopathy is an uncommon vascular lesion characterized by
      segmental arterial stenoses. We reviewed the experience with several management
      algorithms to define the most effective management course. The clinical records
      of 14 pediatric patients with acquired SAA who presented over a 16-year period
      were reviewed. Most patients presented with a mid-thoracoabdominal coarctation
      and were diagnosed with Takayasu arteritis. Differentiating between Takayasu
      arteritis and fibromuscular dysplasia was difficult on clinical grounds or by
      angiography. Medical management of the end-organ disease and renovascular
      hypertension was only palliative. Selective percutaneous transluminal balloon
      angioplasty of the stenotic renal arteries had only transient benefits; renal
      autotransplantation had slightly better success. Dilation of stenosed aortic
      segments with balloon-expandable endovascular stents and subsequent renal
      autotransplantation proved useful. Distinguishing SAA resulting from
      fibromuscular dysplasia caused by Takayasu arteritis in the chronic vaso
      occlusive phase may be unnecessary for effective treatment. Therapy should focus
      on interventions to minimize the end-organ damage caused by the vaso-occlusive
      manifestations of the disorders.

PMID- 9627597
TI  - Relations of body composition to left ventricular geometry and function in
      children.
AB  - OBJECTIVE: To determine whether body composition and fasting insulin levels
      explained variation in left ventricular (LV) function and geometry. PARTICIPANTS:
      Sixty-two children, 7 to 13 years of age. RESULTS: For LV mass/height the partial
      correlation (age controlled) with percentage of fat was r = 0.34 (p = 0.008) and
      the correlation with (Ln)insulin was r = 0.25 (p = 0.051); multiple regression
      showed that independent proportions of the variance were explained by gender
      (boys > girls), ethnicity (black > white subjects), and percentage of fat (p =
      0.015). Nonnormalized LV mass was correlated (age controlled) with fat-free mass
      (r = 0.76; p < 0.001), fat mass (r = 0.58; p < 0.001), and (Ln) insulin (r =
      0.27; p = 0.0359); multiple regression showed that fat-free mass and fat mass
      explained independent proportions of the variance. Percentage of fat was
      correlated (age controlled) with greater relative wall thickness (r = 0.34; p =
      0.008) and lower midwall fractional shortening (-0.37; p = 0.004). CONCLUSION:
      Body fatness was cross-sectionally associated with levels of LV function and
      geometry that in adults have been found to lead to morbidity and death. The
      relationship of fatness to LV mass may be due to the higher insulin
      concentrations in the fatter children. These cross-sectional results are
      consistent with the hypothesis that excess fatness may adversely influence
      cardiovascular health early in life.

PMID- 9627598
TI  - Asymmetric otolith vestibulo-ocular responses in children with idiopathic
      scoliosis.
AB  - OBJECTIVE: A suggested cause of idiopathic scoliosis (IS) in children is a
      disequilibrium in the vestibulospinal control of trunk muscles. We sought a
      correlation between otolith vestibular dysfunction and IS. METHODS: A recently
      developed test for evaluation of otolith vestibular function (off-vertical axis
      rotation, OVAR) was applied to 30 children with IS, 12 control subjects, and 3
      with congenital scoliosis as a result of spinal deformities. RESULTS: Of the
      patients with IS, 67% had significantly greater values of directional
      preponderance on the OVAR test (a measure of otolith system imbalance) compared
      with control subjects. Patients with congenital scoliosis showed normal responses
      on the OVAR test. No correlation was found between the direction of the
      preponderance and the side of the spine imbalance, or between the directional
      preponderance and the curve magnitude. The rate of progression of the scoliosis
      was not significantly correlated with the amplitude of the directional
      preponderance. CONCLUSION: These results support the hypothesis that central
      otolith vestibular system disorders lead to a vestibulospinal system imbalance,
      and may be a factor in the cause of IS.

PMID- 9627599
TI  - When they grow up: the growth of extremely low birth weight (< or = 1000 gm)
      infants at adolescence.
AB  - The growth of 32 extremely low birth weight infants (1000 gm or less) was
      determined at adolescence. Their height, weight, and head circumference were
      measured twice in the first year of life and then at ages 2, 3, 5, 8, 10 years,
      and during adolescence (12 to 18 years). The mean height, weight, and head
      circumference of the adolescents were at the 50th percentile. Female heights were
      > or = their mothers; male heights were in the same or greater percentile than
      those of their fathers. Extremely low birth weight infants experience "catch-up"
      growth up to and into adolescence and attain predicted biparental genetic height.

PMID- 9627600
TI  - Severe congenital hypopituitarism with low prolactin levels and age-dependent
      anterior pituitary hypoplasia: a clue to a PIT-1 mutation.
AB  - A 20-month-old boy presented with severe congenital growth hormone, thyrotropin,
      and prolactin deficiencies resulting from a de novo mutation of the PIT-1 gene.
      This form of congenital hypopituitarism should be suspected if pituitary anatomy
      is normal, especially if prolactin levels are low and, in boys, if the external
      genitalia are normal. Pituitary atrophy appears to be an age-dependent phenomenon
      in this condition.

PMID- 9627601
TI  - Treatment of hemoglobin Bart's hydrops with bone marrow transplantation.
AB  - A 21-month-old girl with hemoglobin Bart's hydrops received bone marrow
      transplantation (BMT) from a matched sibling. No major BMT-related complications
      developed. Hemoglobin levels remained greater than 10 gm/dl for 20 months without
      blood transfusion support despite the presence of residual host hemopoietic cells
      from 2 months after BMT. We suggest consideration of this therapeutic option for
      surviving patients.

PMID- 9627602
TI  - Combined liver-kidney transplantation in methylmalonic acidemia.
AB  - A 13-year-old boy with non-B12-responsive methylmalonic acidemia (MMA) had
      chronic renal failure. Hemodialysis led to symptomatic and biochemical
      improvement. He subsequently received a combined liver-kidney transplant. After
      16 months of follow-up he has a normal lifestyle and a marked reduction in plasma
      and urine methylmalonate.

PMID- 9627603
TI  - Gilbert syndrome caused by a homozygous missense mutation (Tyr486Asp) of
      bilirubin UDP-glucuronosyltransferase gene.
AB  - We report a case of Gilbert syndrome caused by a homozygous missense mutation
      (Tyr486Asp) of the bilirubin UDP-glucuronosyltransferase gene. Homozygous
      missense mutations of the gene have previously been recognized as responsible for
      Crigler-Najjar syndrome type II. We conclude that Gilbert syndrome in some
      patients results from homozygous missense mutations of the UDP
      glucuronosyltransferase gene.

PMID- 9627604
TI  - Antibody-negative chronic hepatitis C virus infection in immunocompetent
      children.
AB  - Antibody-negative hepatitis C virus (HCV) infection, defined by the presence of
      HCV viremia in the absence of a serologic response to HCV, was detected in two
      immunocompetent and symptom-free children; each had a history of exposure to
      blood products. HCV infection may occasionally explain cryptogenic elevation of
      aminotransferases, even in the absence of serum anti-HCV. HCV-RNA should be
      investigated in these cases, particularly in the presence of previous exposure to
      blood products.

PMID- 9627605
TI  - Culture-negative endocarditis caused by Bartonella henselae.
AB  - A 4-year-old girl presented with clinical evidence of infective endocarditis
      involving her aortic valve, but blood cultures were sterile. Serologic studies
      and analysis of resected valve by immunohistochemistry and polymerase chain
      reaction established the diagnosis of Bartonella henselae endocarditis.
      Clinicians should be aware that B. henselae can cause apparent culture-negative
      endocarditis in children.

PMID- 9627606
TI  - Perianal granuloma caused by Enterobius vermicularis: report of a new observation
      and review of the literature.
AB  - The literature reports 12 cases of enterobiasis presenting as perianal abscess or
      granuloma. We describe an additional case of a perianal granuloma containing
      Enterobius vermicularis eggs in a 5-year-old boy. We suggest routine parasite
      screening for all children presenting with this condition.

PMID- 9627607
TI  - Partial splenic embolization for treatment of disseminated intravascular
      coagulation in lymphangiomatosis.
AB  - A 1-year-old boy presented with pericardial effusion, pulmonary infiltrates, and
      disseminated intravascular coagulation; lung biopsy indicated pulmonary
      lymphangiomatosis. He did not respond to medical therapy and was a poor surgical
      candidate; therefore, he underwent partial splenic embolization. The procedure
      resulted in a complete disappearance of the DIC and marked improvement in his
      cardiorespiratory status. He continues to thrive and is transfusion-independent 2
      years after the procedure.

PMID- 9627608
TI  - Lidocaine iontophoresis for topical anesthesia before intravenous line placement
      in children.
AB  - In a double-blind randomized trial including 42 children aged 7 to 18 years, less
      pain occurred with intravenous placement after iontophoresis of 2% lidocaine with
      epinephrine, as reported by patients (p = 0.005), parents (p = 0.001),
      intravenous personnel (p = 0.009), and investigators (p = 0.0002) compared with
      placebo therapy. Lidocaine iontophoresis provides rapid and effective topical
      anesthesia for intravenous access in children.

PMID- 9627609
TI  - Chylothorax and chylopericardium: a complication of a central venous catheter.
AB  - This article describes a rare and severe complication of central venous
      catheterization, namely extensive thrombosis within the venous system of the
      chest resulting in bilateral chylothorax and chylopericardium. The complication
      resolved with drainage, catheter removal, and low molecular weight heparin
      therapy.

PMID- 9627610
TI  - A new tissue adhesive for laceration repair in children.
AB  - To determine the effectiveness of a new tissue adhesive, 2-Octylcyanoacrylate (2
      OCA), for laceration repair, 83 children presenting to T.C. Thompson Children's
      Hospital Emergency Department with lacerations meeting eligibility requirements
      between February and June 1996 were randomized to receive 2-OCA or nonabsorbable
      sutures/staples. The length of time for repair was recorded. The length of time
      for laceration repair was decreased (2.9 minutes 2-OCA vs 5.8 minutes
      suture/staple; p < 0.001), the parents' assessment of the pain felt by their
      children in the 2-OCA group was less, and the wounds closed with tissue adhesive
      had slightly lower cosmesis scores. 2-OCA is an acceptable alternative to
      conventional methods of wound repair with comparable cosmetic outcome.

PMID- 9627611
TI  - Mortality conference: twin-to-twin transfusion.

PMID- 9627612
TI  - Preoperative fasting: is the answer clear?

PMID- 9627613
TI  - Obstructive sleep apnea and growth in children with cleft palate.

PMID- 9627614
TI  - Potassium metabolism in extremely low birth weight infants.

PMID- 9627615
TI  - Outcome of acetaminophen overdose.

PMID- 9627616
TI  - Concern over the issue of WIC participant reenrollment.

PMID- 9627617
TI  - ADA testifies on value of nutrition education as Congress considers
      reauthorization of child nutrition programs.

PMID- 9627618
TI  - When the expert in residence is you. Wielding the tools the NCND dietitians use
      to answer questions about food and nutrition science.

PMID- 9627619
TI  - Improvements are needed in hospital diets to meet dietary guidelines for health
      promotion and disease prevention.

PMID- 9627620
TI  - Energy intake and glycemia in lactating women with type 1 diabetes.
AB  - OBJECTIVE: To describe glycemia and insulin administration in lactating women
      with type 1 diabetes and compare their energy intake, lactation onset, and
      postpartum weight to lactating women without diabetes. DESIGN: A prospective
      observational study conducted at 2, 3, 6, 14, 42, and 84 days postpartum. Insulin
      dosage and glucose levels after fasting and at 80 and 110 minutes after eating
      (by measuring capillary blood glucose concentrations and glycated hemoglobin
      [HbA1c] values) are described for women with type 1 diabetes. Dietary intake,
      weight, and lactation onset for women with type 1 diabetes are compared with
      those without the disease. SUBJECTS/SETTING: Fourteen lactating women with type 1
      diabetes and 25 women without diabetes (control subjects) were recruited from
      private obstetrician offices and high-risk prenatal clinics at 3 major medical
      centers. STATISTICAL ANALYSES: A repeated-measures 2-factor analysis of variance
      was used to determine group, time, and interaction effects between women with
      type 1 diabetes and the control group at 2, 3, 7, 14, 42, and 84 days postpartum.
      RESULTS: Seven women with type 1 diabetes breast-fed through 84 days postpartum,
      although they perceived later onset of milk and had fasting and postprandial
      hyperglycemia. Their HbA1c levels increased by 20%, confirming relative
      hyperglycemia. After adjustment for prepregnancy weight, women with type 1
      diabetes consumed 7 kcal fewer per kilogram per day than control subjects.
      Average insulin dose was returned to prepregnancy levels of 45.3 +/- 3.6 U/d
      (least square means +/- standard error of the mean) by 1 week. APPLICATION:
      Achieving desired metabolic control during the establishment of lactation is
      difficult. A better understanding of energy and insulin needs and their
      relationship to lactation in women with type 1 diabetes is needed.

PMID- 9627621
TI  - Preparing pregnant women with diabetes for special breast-feeding challenges.

PMID- 9627622
TI  - Nutrition and feeding in infants with bronchopulmonary dysplasia after initial
      hospital discharge: risk factors for growth failure.
AB  - OBJECTIVE: To identify nutritional risk factors for growth failure in infants
      with bronchopulmonary dysplasia (BPD) after initial hospital discharge, and to
      describe growth in and feeding concerns about these infants after discharge to
      the community. DESIGN: A cohort of 40 infants with BPD was followed up for 7
      monthly visits after initial hospital discharge. Data on potential risk factors
      were gathered prospectively. SUBJECTS/SETTING: Forty infants with BPD were
      recruited from all 4 tertiary-level neonatal intensive care units in the Puget
      Sound area of Washington. Exclusionary criteria included congenital or
      chromosomal anomalies, grade IV intraventricular hemorrhage, and drug or alcohol
      exposure in utero. MAIN OUTCOME MEASURES: Growth failure defined as weight less
      than the 5th percentile on National Center for Health Statistics growth curves at
      2 or more points in time and a decrease in weight-for-age z score during the
      study period. STATISTICAL ANALYSES PERFORMED: Relative risk of growth failure
      with exposure to each risk factor was determined. The chi 2 test was used to
      measure association between growth and development, and change in z scores was
      used to examine growth patterns. RESULTS: Growth failure occurred in 8 of 40
      infants. Twenty-nine of the infants experienced a drop in weight-for-age z score
      from the initial to the final study visit. Growth failure was associated with low
      socioeconomic status (relative risk = 4.0, 95% confidence interval = 1.3, 12.6),
      postdischarge days of illness (relative risk = 10.5, 95% confidence interval =
      1.4, 77.4) and "suspect" development (chi 2 = 7.12, P = .014). APPLICATIONS:
      Infants with BPD may benefit from comprehensive postdischarge nutrition and
      feeding therapy that includes ensuring adequate energy intake, parental support
      and education, and feeding evaluation and therapy.

PMID- 9627623
TI  - Prenatal and perinatal factors associated with breast-feeding initiation among
      inner-city Puerto Rican women.
AB  - OBJECTIVE: To identify factors associated with the initiation of breast-feeding
      in a predominantly Puerto Rican population living in inner-city Hartford, Conn.
      DESIGN: Retrospective study of 144 Latino women (mean +/- standard deviation age
      = 26.3 +/- 5.7 years) with children at least 1 year old but younger than 6 years
      old (mean +/- standard deviation age = 3.0 +/- 1.2 years) at the time of the
      survey. Women were recruited from agencies sponsoring health programs for mothers
      and children. They were interviewed in their homes (69%) or at the Hispanic
      Health Council, Hartford, Conn (31%). SUBJECTS/SETTING: Low-income Latino women
      who had at least 1 preschooler at the time of the interview. The women lived in
      inner-city Hartford, and the overwhelming majority were Puerto Rican and received
      welfare assistance and food stamps. Seventy-eight percent of the women chose to
      be interviewed in Spanish; the other 22% were interviewed in English. STATISTICAL
      ANALYSES: Explanatory variables that related to breast-feeding initiation (P < or
      = .2) in bivariate chi 2 analyses were entered into a multivariate logistic
      regression model that was reduced using backward stepwise elimination procedures.
      RESULTS: Multivariate analyses indicated that breast-feeding the previous child,
      shorter length of maternal residence in the United States, not receiving prenatal
      bottle-feeding advice, more recent birth, and higher birth weight were positively
      associated with breast-feeding initiation. A major reason for choosing not to
      breast-feed was that women felt socially uncomfortable doing it. APPLICATIONS:
      Breast-feeding initiation was more likely in Latino women who received prenatal
      breast-feeding counselling and postpartum support. Mothers of low-birth-weight
      infants and women breast-feeding for the first time may need additional help.
      These findings can be used by programs like the Special Supplemental Nutrition
      Program for Women, Infants, and Children to increase breast-feeding initiation.

PMID- 9627624
TI  - Profile of public health nutrition personnel: challenges for population/system
      focused roles and state-level monitoring.
AB  - OBJECTIVE: Our 3 objectives were to document the current public health nutrition
      workforce in the United States, identify top public health nutrition priorities
      for the next 5 years, and assess the capacity of public health nutrition
      personnel to address these priorities and the nutrition-related objectives of
      Healthy People 2000. DESIGN: A census survey was distributed to public health
      nutrition personnel in all state and local health agencies and nonprofit and for
      profit agencies funded by official health agencies throughout the United States
      and US territories. Also, state and territorial nutrition directors were sent a
      different questionnaire. SUBJECTS: Data were collected from 49 states, the
      District of Columbia, and 2 territories; 7,550 public health nutrition personnel
      were represented. STATISTICAL ANALYSIS: Data were analyzed using EpiInfo
      software. Descriptive statistics are presented. RESULTS: Almost half of the
      respondents worked in local or county health agencies and about two thirds were
      involved in direct care services. Only about 40% were registered dietitians and
      about one fourth had a master's degree. Almost 90% of all full-time equivalent
      positions were funded through federal dollars; 78% of all funding was from the
      Special Supplemental Nutrition Program for Women, Infants, and Children. Top
      health concerns identified were diet/nutrition to prevent chronic disease, low
      breast-feeding rates, low birth weight, iron deficiency anemia, and
      obesity/overweight. Public health nutrition personnel will be challenged to
      assume population/system-focused roles and state-level monitoring of Healthy
      People 2000 objectives. Only 2 of the 17 nutrition objectives of Healthy People
      2000 were monitored by more than 50% of the states. APPLICATIONS: If official
      health agencies are to shift to public health core functions, as recommended by
      an Institute of Medicine report, then a substantial proportion of the public
      health nutrition workforce must not only change how they practice but also obtain
      the knowledge and skills to do so. Strategies to improve workforce capacity are
      discussed, including continuing education interventions through professional
      organizations, distance and on-campus educational opportunities through approved
      public health nutrition programs, and advocacy for new funding streams focused on
      public health core functions.

PMID- 9627625
TI  - Allaying fears and fallacies about lactose intolerance.
AB  - Public awareness and misunderstandings of lactose intolerance are at an all-time
      high. Many people erroneously believe they are lactose intolerant or develop
      gastrointestinal symptoms after intake of lactose. Consequently, lactose
      containing foods such as milk and other dairy foods may be eliminated
      unnecessarily from the diet. Because these foods are a major source of calcium,
      low intake of them can compromise calcium nutriture. This, in turn, can increase
      the risk of major chronic diseases such as osteoporosis (porous bones) and
      hypertension. This review is intended to help dietetics professionals alleviate
      clients' fears about lactose intolerance and recommend dietary strategies to
      improve tolerance to lactose. Scientific findings indicate that the prevalence of
      lactose intolerance is grossly overestimated. Other physiologic and psychologic
      factors can contribute to gastrointestinal symptoms that mimic lactose
      intolerance. Scientific findings also indicate that people with laboratory
      confirmed low levels of the enzyme lactase can consume 1 serving of milk with a
      meal or 2 servings of milk per day in divided doses at breakfast and dinner
      without experiencing symptoms. Several dietary strategies are available to help
      lactose maldigesters include milk and other dairy foods in their diet without
      experiencing symptoms.

PMID- 9627626
TI  - Taxonomic classification helps identify flavonoid-containing foods on a
      semiquantitative food frequency questionnaire.
AB  - We describe foods on the National Cancer Institute (NCI) semiquantitative food
      frequency questionnaire with respect to their botanical taxonomic classification
      and the likely presence of flavonoids. Foods listed in the NCI questionnaire were
      classified for potential flavonoid content using information from Linnaean
      taxonomic classification and processing techniques known to modify flavonoid
      content. The outcome measure was flavonoid presence in foods as evidenced in the
      food composition analytical literature. We then verified the presence of 6
      classes of flavonoids in these foods by searching the chemical analytical
      literature (represented by Food Science and Technology Abstracts Service from
      January 1969 to June 1996). One hundred ninety foods were mentioned on the NCI
      questionnaire; after duplications were removed, 153 foods remained. Data obtained
      from literature searches indicated that 54 foods (35%) contained flavonoids. An
      additional 19 recipe foods (12%) had flavonoid-containing components or
      ingredients. Thirty-nine foods (25%) had flavonoids that had been reduced or
      removed during milling and other processing. Seven foods (5%) were stripped and
      judged to have no flavonoids. Thirty-four foods (22%), for example, dairy, meat,
      and sugar, were completely devoid of flavonoids. When food composition data are
      unavailable, botanical taxonomic classifications may be helpful in ascertaining
      the likely presence of flavonoids in foods. However, quantitative estimates are
      likely to be imprecise.

PMID- 9627627
TI  - Insulin misuse by women with type 1 diabetes mellitus complicated by eating
      disorders does not favorably change body weight, body composition, or body fat
      distribution.

PMID- 9627628
TI  - Who eats 5 a day?: intake of fruits and vegetables among Norwegians in relation
      to gender and lifestyle.

PMID- 9627629
TI  - Ratings of food courses and culinary training components in dietetics education.

PMID- 9627630
TI  - Dietary Reference Intakes: the new basis for recommendations for calcium and
      related nutrients, B vitamins, and choline.
AB  - Dietary Reference Intakes (DRIs) represent the new approach adopted by the Food
      and Nutrition Board to providing quantitative estimates of nutrient intakes for
      use in a variety of settings, replacing and expanding on the past 50 years of
      periodic updates and revisions of the Recommended Dietary Allowances (RDAs). The
      DRI activity is a comprehensive effort undertaken to include current concepts
      about the role of nutrients and food components in long-term health, going beyond
      deficiency diseases. The DRIs consist of 4 reference intakes: the RDA, which is
      to be used as a goal for the individual; the Tolerable Upper Intake Level (UL),
      which is given to assist in advising individuals what levels of intake may result
      in adverse effects if habitually exceeded; the Estimated Average Requirement
      (EAR), the intake level at which the data indicate that the needs for 50% of
      those consuming it will not be met; and the Adequate Intake (AI), a level judged
      by the experts developing the reference intakes to meet the needs of all
      individuals in a group, but which is based on much less data and substantially
      more judgment than that used in establishing an EAR and subsequently the RDA.
      When an RDA cannot be set, an AI is given. Both are to be used as goals for an
      individual. Two reports have been issued providing DRIs for nutrients and food
      components reviewed to date: these include calcium and its related nutrients:
      phosphorus, magnesium, vitamin D, and fluoride; and most recently, folate, the B
      vitamins, and choline. The approaches used to determine the DRIs, the reference
      values themselves, and the plans for future nutrients and food components are
      discussed.

PMID- 9627631
TI  - Eye injuries caused by bungee cords.

PMID- 9627632
TI  - Retinopathy of prematurity guidelines.

PMID- 9627633
TI  - Surgical treatment of parasitic cysts.

PMID- 9627634
TI  - Avoiding Tenon's capsule.

PMID- 9627635
TI  - Avoiding Tenon's capsule.

PMID- 9627636
TI  - Posterior capsule opacification after cataract surgery.

PMID- 9627637
TI  - Clear lensectomy and implantation of IOL for high myopia.

PMID- 9627638
TI  - Syphilis exposure and uveitis.

PMID- 9627639
TI  - Microsurgery for eyelid margin tumors.

PMID- 9627640
TI  - Prism Adaptation Study.

PMID- 9627641
TI  - Cataract surgery in patients with diabetes.

PMID- 9627642
TI  - Pseudoexfoliation syndrome for the comprehensive ophthalmologist. Intraocular and
      systemic manifestations.
AB  - BACKGROUND: Renewed interest in pseudoexfoliation syndrome (PEX) may be
      attributed to an increased awareness of many clinical risks not only for open
      angle glaucoma and its recent recognition as a generalized disorder. This review
      summarizes the range of intraocular and extraocular manifestations. Involvement
      of all tissues of the anterior segment of the eye results in a spectrum of
      intraocular complications that have management implication for all practicing
      ophthalmologists. DESIGN: The study design was a review. METHODS: Clinical
      diagnosis depends on biomicroscopy, biocytology, and laser-tyndallometry.
      Laboratory research methods range from light and electron microscopy, to
      immunohistochemical and molecular biologic approaches. OBSERVATIONS: Clinical
      histopathologic correlations focus on the involvement of lens (PEX-phacopathy),
      zonular apparatus (zonulopathy), ciliary body (cyclopathy), iris (iridopathy),
      trabecular meshwork (trabeculopathy), and cornea (corneal endotheliopathy)
      leading to the following complications: (1) open-angle glaucoma as well as angle
      closure glaucoma due to pupillary and ciliary block; (2) phacodonesis, lens
      dislocation, and increased incidence of vitreous loss in extracapsular cataract
      surgery caused by alterations of the zonular apparatus and its insertion into the
      ciliary body and lens; (3) blood-aqueous barrier breakdown (pseudouveitis),
      anterior chamber hypoxia, iris stromal hemorrhage, pigment epithelial melanin
      dispersion, poor or asymmetric pupillary dilatation, and formation of posterior
      synechiae due to involvement of all cell populations of the iris; and (4) early
      diffuse corneal endothelial decompensation explained by a damaged and numerically
      reduced endothelium. CONCLUSIONS: In view of the multitude of clinical
      complications, PEX is of relevance to comprehensive ophthalmologists, including
      specialists in glaucoma, cataract, cornea, neuro-ophthalmology, and retina.
      Special attention to the risks associated with PEX is advised before, during, and
      after surgery.

PMID- 9627643
TI  - Central corneal thickness and intraocular pressure in a Mongolian population.
AB  - OBJECTIVE: The purpose of the study was to quantify the variation of central
      corneal thickness (CCT) in an east Asian population and to examine its
      relationship to estimates of intraocular pressure (IOP) made with an applanation
      tonometer. DESIGN: The study design was a cross-sectional, population-based
      survey. PARTICIPANTS: One thousand two-hundred forty-two residents of Hovsgol
      Province, Mongolia, 10 to 87 years of age participated. MAIN OUTCOME MEASURES:
      The CCT was measured using an optical pachymeter in all subjects. The IOP was
      measured using a, Goldmann-type applanation tonometer in subjects 40 years of age
      and older. RESULTS: There was a highly significant decrease in CCT with age: 5
      microns/decade in men and 6 microns/decade in women (both, P < 0.0001). A highly
      significant positive correlation was identified between IOP and CCT. Linear
      regression analysis suggests that between the ages of 40 and 80 years, an
      increase in CCT of 10 microns is associated with an increase in IOP measurements
      of 0.18 mmHg in right eyes (95% confidence interval, 0.12-0.25) and 0.24 mmHg in
      left eyes (95% confidence interval, 0.17-0.31). The authors calculate that
      interindividual differences in CCT may produce a difference in measured IOP of
      between 2.3 and 3.1 mmHg. CONCLUSIONS: Variation in CCT is a significant source
      of variation in IOP measurements between individuals. The authors suggest that
      measurement of corneal thickness should be considered when assessing IOP as a
      risk factor for glaucoma in east Asians.

PMID- 9627644
TI  - Surgical results of combined trabeculotomy-trabeculectomy for developmental
      glaucoma.
AB  - OBJECTIVE: The purpose of the study was to evaluate the surgical outcome of
      combined trabeculotomy-trabeculectomy in different types of primary developmental
      glaucomas. DESIGN: A retrospective review of all cases of primary developmental
      glaucomas that underwent primary combined trabeculotomy-trabeculectomy between
      August 1990 and September 1995, with a minimum follow-up of 6 months, was
      performed. PARTICIPANTS: One hundred and eighty-two eyes of 120 patients were
      included in this study; 122 (67%) eyes had congenital glaucoma; 22 (12.1%) eyes
      had infantile glaucoma; and 38 (20.9%) eyes had juvenile glaucoma. INTERVENTION:
      Primary combined trabeculotomy-trabeculectomy was the chosen intervention. MAIN
      OUTCOME MEASURES: Preoperative and postoperative intraocular pressures, visual
      acuities, success rate, corneal clarity and diameters, bleb characteristics, time
      of surgical failure, and complications were the main outcome measures. RESULTS:
      Intraocular pressure (mean +/- SD) reduced from a preoperative level of 26.5 +/-
      8.3 mmHg; 30.3 +/- 9.9 mmHg; and 31.8 +/- 11.5 mmHg to 13.1 +/- 5.8 mmHg; 13.7 +/
      4.4 mmHg; and 13.3 +/- 6.0 mmHg in the congenital, infantile, and juvenile types
      of developmental glaucomas, respectively. Kaplan-Meier survival analysis showed
      that the success probability at 6 months was 94.4% +/- 2.3%; 90.9% +/- 6.1%; and
      81.0% +/- 7.3% in the three groups, respectively. The success probability of
      patients with juvenile glaucoma was significantly lower than it was for those
      with congenital glaucoma (P = 0.0393). Of 182 eyes, 105 (57.7%) eyes had corneal
      edema at presentation. Eighty-one (79%) of 105 eyes had complete clearance of
      corneal edema postoperatively (P < 0.0001). The follow-up period ranged from 6
      months to 48 months (mean, 10.7 +/- 12.0 months). There were no sight-threatening
      intraoperative and postoperative complications in any patient. CONCLUSIONS:
      Primary combined trabeculotomy-trabeculectomy is safe, effective, and
      sufficiently predictable to be considered the first choice of surgical treatment
      in primary congenital glaucoma with corneal edema. Juvenile glaucoma has the
      worst prognosis, and infantile glaucoma has a better prognosis than does juvenile
      glaucoma.

PMID- 9627645
TI  - Management of large, leaking, and inadvertent filtering blebs with the
      neodymium:YAG laser.
AB  - OBJECTIVE: The purpose of the study was to test the efficacy of the neodymium:YAG
      (Nd:YAG) laser for repairing filtering blebs. DESIGN: The study design was a
      prospective study. PARTICIPANTS: Five eyes of five patients with leaking blebs
      (group 1), five eyes of five patients with large irritating blebs (group 2), and
      four eyes of four patients with inadvertent filtering blebs in the surgical wound
      after cataract surgery (group 3) were studied. INTERVENTION: The thermal mode of
      the Lasag Microrupter II Nd:YAG laser was used to treat the filtering blebs. The
      area of the bleb targeted for treatment was "painted" with methylene blue and
      then exposed to Nd:YAG laser treatment with an energy level of 2.5 to 3.75 J in a
      grid pattern. The aiming beam was focused on the conjunctiva, but the laser beam
      was offset according to the height of the bleb (offset of 0.9-1.5 mm, 4-5 on the
      Lasag) to selectively treat the internal surface of the bleb. MAIN OUTCOME
      MEASURES: Symptomatology, intraocular pressure (IOP), and complications were
      measured. RESULTS: After the laser treatment, all the leaks in group 1 were
      healed, all the patients in group 2 reported relief of their symptoms, and all
      blebs in group 3 shrank considerably. The IOP increased significantly (P < 0.001)
      after laser treatment in all three groups. This elevation appeared to diminish
      over time, with the major increase in IOP being recorded within the first month
      after the laser treatment. However, satisfactory IOP control was maintained in
      nearly all patients (13 to 14) who received none or one antiglaucoma medication.
      The visual acuity of one patient decreased significantly because of cataract
      formation. Complications included transient pressure rise (1 eye), bleb failure
      (1 eye), pupillary retraction toward the bleb (6 eyes), iatrogenic bleb leak (6
      eyes), and cataract (1 eye). CONCLUSION: The continuous wave Nd:YAG laser is an
      effective tool for repairing bleb-related problems while maintaining successful
      filtration.

PMID- 9627646
TI  - Frequency of asymmetric visual field defects in normal-tension and high-tension
      glaucoma.
AB  - OBJECTIVE: The purpose of the study was to evaluate the frequency of asymmetric
      visual field loss at presentation in patients with normal-tension glaucoma (NTG)
      and high-tension glaucoma (HTG). DESIGN: A retrospective cross-sectional study
      design was used. PARTICIPANTS: Four hundred and three NTG patients and 337
      consecutive HTG patients (consecutive diagnoses between 1986 and 1996).
      INTERVENTION: Analysis of the frequency of unilateral field loss presentations in
      NTG and HTG. The visual fields of fellow eyes were compared to determine the side
      of more severe field loss. For the NTG patients, the relationship between the
      side with greater field loss and corresponding intraocular pressure (IOP) was
      investigated. MAIN OUTCOME MEASURES: Humphrey field analyzer mean defect (MD) and
      mean diurnal IOP. RESULTS: In the NTG group, 101 (25%) patients presented with
      unilateral field loss. The proportion of cases with unilateral field loss
      decreased with increasing age of presentation (chi-square test for trend = 26.9;
      P < 0.0001). Sixty-four percent of the patients had unilateral field loss in the
      left eye. Sixty-eight percent of the cases with bilateral field loss had a higher
      MD in the left eye. The diurnal IOP was estimated as 0.23 +/- 0.068 mmHg (mean +/
      SE) higher in the left eye (P = 0.001). In the HTG group, 104 (31%) patients
      presented with unilateral field loss. The proportion of cases with unilateral
      field loss decreased with increasing age of presentation (chi-square test for
      trend = 4.6; P = 0.03). Right and left eyes had an equal chance of having field
      loss in unilateral cases and of being the side of more advanced field damage in
      bilateral cases. CONCLUSIONS: The frequency of cases with unilateral field loss
      was similar in HTG and NTG patients. Patients with unilateral field loss at
      presentation were more likely to be at the younger end of the age range. In the
      NTG population we studied, the left eye was more frequently the side of onset of
      field loss and 2.1 times more likely to present with a greater field defect than
      the right eye. In HTG patients, right and left eyes showed an equal chance of
      being the side of onset of field damage and the more affected side.

PMID- 9627647
TI  - Long-term postoperative results of a consecutive series of stages 4 and 5
      retinopathy of prematurity.
AB  - OBJECTIVE: The purpose of the study was to assess the long-term, anatomic, and
      functional results of a consecutive series of stages 4 and 5 retinopathy of
      prematurity (ROP) eyes after surgical management. DESIGN: A retrospective
      analysis of 42 eyes of 21 children yielded 34 eyes of 19 children who were
      operated on for stages 4 and 5 ROP. PARTICIPANTS: In 33 of 34 eyes, it was
      possible to have age-appropriate vision testing. The children were followed for a
      mean of 44 months. RESULTS: Seventy-six percent of eyes (25 of 33) in which
      vision testing was possible had partial or complete attachment of the posterior
      pole. Fifteen percent of all eyes achieved 20/300 or better visual acuity. Thirty
      percent of all eyes achieved 20/800 or better visual acuity. Forty-eight percent
      of eyes achieved ambulatory vision of 20/ 1900 visual acuity or better, and 72%
      of eyes achieved light perception or better vision. All eyes were managed
      similarly for their preoperative screening, surgical therapy, and postoperative
      refractive correction by one vitreoretinal surgeon and one pediatric
      ophthalmologist. CONCLUSION: Timely surgical intervention and appropriate
      postoperative care can result in useful vision in stages 4 and 5 ROP.

PMID- 9627648
TI  - The 14-year incidence of visual loss in a diabetic population.
AB  - OBJECTIVE: The purpose of the study was to estimate the 14-year incidence of
      visual loss in a diabetic population and to examine its relationship to potential
      risk factors. DESIGN: Cohort study. PARTICIPANTS: A population-based sample of
      younger onset diabetic persons diagnosed younger than 30 years of age and taking
      insulin (n = 880) were examined at baseline, 4 years, 10 years, and 14 years.
      INTERVENTION: Visual acuity (VA) as measured by the Early Treatment Diabetic
      Retinopathy Study protocol was performed. MAIN OUTCOME MEASURES: Visual
      impairment (VI), defined as a VA of 20/40 or worse in the better eye; blindness,
      defined as a VA of 20/200 or worse in the better eye; and doubling of the visual
      angle were measured. RESULTS: Cumulative 14-year incidences of VI, doubling of
      the visual angle, and blindness were 12.7%, 14.2%, and 2.4%, respectively. In
      univariate analyses, loss of vision as measured by doubling of the visual angle
      is associated with older age, longer duration of diabetes, higher glycosylated
      hemoglobin, higher systolic and diastolic blood pressure, presence of
      proteinuria, more pack-years smoked, presence of macular edema, and more severe
      retinopathy. In logistic regression analyses, incidence of doubling of the visual
      angle is associated independently with retinopathy (odds ratio [OR], 1.07; 95%
      confidence interval [CI], 1.03, 1.11 for each level), glycosylated hemoglobin
      (OR, 1.46; 95% CI, 1.28, 1.66 for each 1%), proteinuria (OR, 2.32; 95% CI, 1.39,
      3.88 for presence), and age (OR, 1.45; 95% CI, 1.20, 1.75 for 10 years). In
      addition, a change in glycosylated hemoglobin from baseline to the 4-year
      examination is associated with loss of vision (OR, 1.15; 95% CI, 1.02, 1.30 for a
      1% increase). CONCLUSIONS: Loss of vision continues to be significant in persons
      with diabetes. These results suggest that prevention of retinopathy through
      control of glycemia will have a beneficial effect on visual outcome.

PMID- 9627649
TI  - Nosocomial acute-onset postoperative endophthalmitis survey. A 10-year review of
      incidence and outcomes.
AB  - OBJECTIVE: The purpose of the study was to evaluate the incidence of acute-onset
      (within 6 weeks after surgery) postoperative endophthalmitis and to assess the
      visual acuity outcomes after treatment over a 10-year period at one institution.
      PATIENTS AND METHODS: This retrospective study reviews all surgical cases
      performed between January 1, 1984 and December 30, 1994 at the Anne Bates Leach
      Eye Hospital, Bascom Palmer Eye Institute, University of Miami Medical Center,
      for the occurrence of nosocomial acute-onset postoperative endophthalmitis.
      RESULTS: The overall 10-year incidence of acute-onset postoperative
      endophthalmitis after intraocular surgery was 0.093% (54/58, 123). The incidences
      of culture-proven acute-onset postoperative endophthalmitis by surgical category
      were as follows: cataract surgery with or without intraocular lens (IOL) (0.082%,
      34/41, 654), pars plana vitrectomy (PPV) (0.046%, 3/6557), penetrating
      keratoplasty (0.178%, 5/2805), secondary IOL placement (0.366%, 5/1367), glaucoma
      surgeries (0.124%, 4/3233), combined trabeculectomy and cataract surgery (0.114%,
      2/1743), and combined penetrating keratoplasty and cataract surgery (0.194%,
      1/515). The median visual acuity after endophthalmitis treatment was 20/200. The
      median visual acuities after endophthalmitis treatment by procedure were as
      follows: cataract surgery with or without IOL (20/133), PPV (no light
      perception), penetrating keratoplasty (2/200), secondary IOL implantation
      (20/40), glaucoma surgery (20/80), and combined trabeculectomy and cataract
      surgery with or without IOL (20/150). CONCLUSIONS: The overall incidence of
      endophthalmitis after intraocular surgery was 0.093%. The incidence of
      endophthalmitis was higher after secondary IOL implantation than after cataract
      extraction (P = 0.008, Fisher's exact test). After treatment, the visual acuity
      outcomes were worse in the patients who developed endophthalmitis after PPV than
      after cataract extraction, glaucoma procedures, or secondary IOL implantation (P
      < 0.05, analysis of variance, Duncan's multiple range test). Acuity outcomes
      after treatment of endophthalmitis were better among the patients with secondary
      IOL implantation than after penetrating keratoplasty or PPV (P < 0.05, analysis
      of variance, Duncan's multiple range test). The results of this 10-year review
      from a large teaching center may serve as a source of comparison for other
      centers and future studies.

PMID- 9627650
TI  - Removal of dislocated intraocular lenses using pars plana vitrectomy with
      placement of an open-loop, flexible anterior chamber lens.
AB  - OBJECTIVE: There are many alternatives available to the vitreoretinal surgeon in
      the management of posteriorly dislocated intraocular lenses (IOL). The lens may
      be repositioned in the ciliary sulcus if there is adequate capsular support, but
      if this support is absent, it must either be sutured in place (to the sclera or
      iris) or exchanged for an anterior chamber (AC) IOL. Scleral-sutured IOLs can be
      associated with hemorrhage, cystoid macular edema, retinal detachment, and
      endophthalmitis (through the suture tract), and use sutures that must last for
      the lifetime of the patient. Anterior chamber IOLs (ACIOLs) are easier to implant
      but require a limbal incision for insertion. The authors sought to determine the
      safety and efficacy of combining removal of posteriorly dislocated IOLs with
      ACIOL placement. DESIGN: A retrospective chart review, in which all cases of
      dislocated IOLs managed at the authors' institution over the last 5 years were
      reviewed. Patient characteristics, pre-existing ocular conditions, preoperative
      visual acuity (VA), intraocular pressure (IOP), type of lens dislocated,
      operation performed, postoperative VA and IOP, and length of follow-up were
      recorded. RESULTS: A total of nine cases were identified. Seven of these
      underwent primary posterior chamber (PC) IOL removal with ACIOL implantation. One
      had an ACIOL placed after a sulcus-sutured PCIOL dislocated, and one had enough
      capsular support for placement of a PCIOL after removal of a plate haptic
      silicone lens. Of the seven primary ACIOL cases, the best-corrected VA improved
      in five cases, was unchanged in one (remained 20/20), and declined in another.
      The final postoperative VA (mean follow-up, 12 months) was 20/30 or better in
      five patients, and was limited by age-related macular degeneration and epiretinal
      membrane in the other two. A hyphema occurred in two patients and cleared in both
      without visual compromise. There was no evidence of corneal compromise or
      exacerbation of glaucoma in any of the patients. CONCLUSIONS: Given that the
      results and complication rates in this small series appear to be similar to those
      reported for sulcus-suture techniques, implantation of an ACIOL after removal of
      a posteriorly dislocated IOL appears to be a viable alternative to suture
      fixation in the absence of capsular support.

PMID- 9627651
TI  - Familial exudative vitreoretinopathy. Results of surgical management.
AB  - OBJECTIVE: The purpose of the study was to report the results of surgical
      management of familial exudative vitreoretinopathy (FEVR). DESIGN: The study
      design was a retrospective clinical study. PARTICIPANTS: A consecutive series of
      52 eyes of 26 patients with FEVR were studied. INTERVENTION: All eyes underwent a
      complete ocular examination and were graded using a new classification system.
      Depending on the severity of disease, eyes were treated with peripheral laser
      photocoagulation, scleral buckling, or vitrectomy. MAIN OUTCOME MEASURES:
      Preoperative and postoperative visual functions and anatomic status of the macula
      were the main parameters evaluated. RESULTS: A total of 40 eyes were treated.
      Seven eyes required no treatment and five eyes had inoperable retinal
      detachments. Fifteen eyes were treated with peripheral laser ablation initially
      and 25 eyes presenting with retinal detachments required vitreoretinal surgery.
      Of the 15 eyes treated initially with laser, 8 eyes required no further
      treatment, whereas 7 eyes progressed to retinal detachment requiring
      vitreoretinal surgery. A total of 32 eyes (including 7 previously lasered eyes)
      underwent vitreoretinal surgery. Twenty-nine of these 32 eyes had at least 6
      months of follow-up. At the last follow-up visit, the macula was attached
      completely in 18 eyes (62.1%). Visual acuity ranged from 20/25 to light
      perception, with 10 (34.5%) of the 29 eyes achieving Snellen acuities of 20/100
      or better. Two eyes (6.3%) progressed to no light perception. CONCLUSION: These
      data suggest that surgical intervention can be beneficial in selected cases of
      FEVR.

PMID- 9627652
TI  - Retinal and choroidal manifestations of cat-scratch disease.
AB  - OBJECTIVE: The ability to diagnose cat-scratch disease (CSD) has been facilitated
      greatly by the recent isolation and characterization of Bartonella henselae
      (formerly genus Rochalimaea) and Afipia felis and by the subsequent development
      of specific enzyme-linked immunosorbent assay (ELISA) serologic tests. This study
      will help define the patterns of posterior segment ocular involvement in patients
      with confirmed CSD. DESIGN: The study design is a retrospective case study and
      literature review. PARTICIPANTS: Two consecutive patients with acute visual loss
      from retinal manifestations of CSD participated. INTERVENTIONS: The diagnosis was
      confirmed by B. henselae ELISA testing. Patients underwent extensive medical and
      ophthalmic investigations to exclude other causes of retinal and choroidal
      disease. Ophthalmic investigation included fluorescein angiography and visual
      field testing. One patient received antibiotic therapy with cefotaxime, then with
      ciprofloxacin, and was treated with oral prednisone. The other patient was
      improving for several weeks before oral doxycycline was given. MAIN OUTCOME
      MEASURES: The clinical syndromes observed were studied over time using visual
      acuity, visual field, and clinical findings. Data were collated with cases from
      the literature. RESULTS: Unilateral neuroretinitis and an unusual macular
      retinitis developed in patient 1, as did bilateral small intraretinal white spots
      and a unilateral choroidal infiltrate that continued to develop while the patient
      received antibiotic treatment. Patient 2 had a branch arteriolar occlusion in
      relation to a perivascular retinal infiltrate and a few small, bilateral,
      intraretinal white spots. There was gradual resolution with visual improvement
      while the patient received the antibiotic treatment, although therapeutic
      efficacy could not be determined. Patient 1 also received oral corticosteroids. A
      detailed analysis of the literature placed these findings in context.
      CONCLUSIONS: An unusual, well-defined retinal opacification with features of both
      multiple retinal arteriolar occlusions and a low-grade retinitis was described.
      Several features also may occur in posterior segment CSD, including
      neuroretinitis, a retinal white spot syndrome, and focal choroiditis.

PMID- 9627653
TI  - Multiple cases of acquired toxoplasmosis retinitis presenting in an outbreak.
AB  - OBJECTIVE: The purpose of the study was to examine the variability in
      presentation and outcome of individuals presenting with acquired toxoplasmosis
      retinitis in the setting of an outbreak of the disease. DESIGN: The study design
      was a case series. PARTICIPANTS: Twenty-one eyes of 20 patients with equal gender
      distribution and a mean age of 54 years followed for 38 to 170 weeks (mean 113.7
      weeks) were studied. INTERVENTION: Systemic antimicrobials and corticosteroids
      when indicated were given. MAIN OUTCOME MEASURES: Visual acuity, media
      inflammation and clarity, resolution of active retinitis, and appearance of
      recurrence were observed. RESULTS: Fifteen of 21 lesions were active, and 7 of
      the total number of lesions fell within the macula-peripapillary region. Overall,
      vision improved with treatment except in cases of macular involvement (3 cases)
      and persistent vitritis (3 cases). Four recurrences have occurred to date.
      CONCLUSIONS: This is the largest reported outbreak of acquired toxoplasmosis
      retinitis occurring within a single outbreak. Twenty-one eyes of 20 patients
      presented with retinal lesions, and on average, those treated for active
      retinitis had improvement in vision.

PMID- 9627654
TI  - Microangiopathy of the brain, retina, and cochlea (Susac syndrome). A report of
      five cases and a review of the literature.
AB  - OBJECTIVE: This study reports five new cases of microangiopathy of the brain,
      retina, and cochlea (Susac syndrome) and reviews the world's literature. DESIGN:
      Five cases were systematically studied by the authors. The cases in the
      literature were identified through Medline searches for Susac syndrome;
      microangiopathy of the brain, retina, or ear; and cross-referencing the indexes
      of each retrieved article. PARTICIPANTS: The number of new patients studied in
      this report was five. An additional 41 patients were culled from the literature.
      INTERVENTION: Patients were treated with corticosteroids, antineoplastic agents,
      and other methods in a noncontrolled, nonrandomized fashion. MAIN OUTCOME
      MEASURES: With respect to therapeutic intervention, the main clinical outcome
      measures were return of vision, improvement of neurologic and psychiatric
      manifestations, and recovery of auditory function. Alterations of abnormalities
      observed by cranial magnetic resonance imaging also were monitored. RESULTS: Of
      46 identified patients, 39 were women. The mean age of the patients was 30 years.
      Forty-one patients (89%) had arterial occlusions, which were bilateral in 60%.
      Thirty-one patients (67%) reported hearing loss. Twenty patients (44%) had a
      global encephalopathy, but other neurologic manifestations were common. The mean
      duration of the illness was 46.7 months. CONCLUSION: This rare syndrome is more
      common than previously thought, has a strong female preponderance, and often can
      be identified at an early stage with a careful history and physical examination.
      Magnetic resonance imaging of the brain often shows lesions suggestive of
      multiple sclerosis. Fluorescein angiography may show arteriolar wall
      hyperfluorescence. Early treatment with corticosteroids often is, although not
      invariably, associated with a good prognosis. The disease appears to be self
      limited in most patients.

PMID- 9627655
TI  - What happens to untreated asymptomatic retinal breaks, and are they affected by
      posterior vitreous detachment?
AB  - OBJECTIVE: The purpose of the study was to ascertain the natural consequences of
      asymptomatic retinal breaks and to learn what effects, if any, the occurrence of
      posterior vitreous detachment (PVD) has on such breaks. DESIGN: This was a cohort
      study of consecutive asymptomatic phakic patients, all of whom had asymptomatic
      retinal breaks, observed without treatment over periods of 1 to 33 years
      (average, 11 years). PARTICIPANTS: There were 196 patients with 235 involved
      eyes. INTERVENTION: Periodic clinical examinations, including binocular indirect
      ophthalmoscopy with scleral indentation on all eyes and posterior vitreous
      examination on 50 eyes, were performed. RESULTS: In the total study period, one
      small peripheral retinal detachment developed, without symptoms, from a previous
      subclinical detachment over a period of 14 years. Nineteen eyes (8%) originally
      had or developed 22 areas of subclinical detachment, 2 of which were treated
      because of moderate extension, even though remaining subclinical and without
      symptoms. Ten eyes encountered acute PVDs, which caused symptomatic retinal tears
      in three eyes, one of which also had a clinical retinal detachment. Of the 50
      asymptomatic eyes examined with Goldmann lens and slit lamp, 12 (24%) were found
      to have an existing PVD, which had not led to any complication of the previous
      retinal breaks in any eye. CONCLUSIONS: Asymptomatic retinal breaks discovered in
      phakic primary eyes do not show any significant tendency toward clinical retinal
      detachment, with the exception of a few of those cases that progress to
      subclinical retinal detachment. It is only some of these, comprising 1% to 2% of
      the total group, that may justify treatment. Posterior vitreous detachment
      coexists safely with asymptomatic retinal breaks in phakic primary eyes and shows
      no tendency to provoke complications to pre-existing breaks at the time of its
      occurrence.

PMID- 9627656
TI  - Volumetric analysis of early macular edema with the Heidelberg Retina Tomograph
      in diabetic retinopathy.
AB  - OBJECTIVE: This study describes a new method for the quantification of diabetic
      macular edema by volumetric analysis with the Heidelberg Retina Tomograph (HRT)
      scanning laser ophthalmoscope. DESIGN: Topographic images of the macula were
      obtained in 25 consecutive patients who fitted the inclusion criteria. Twenty age
      matched control subjects were randomly selected for a similar examination.
      PARTICIPANTS: Twenty normal control eyes and 32 eyes of 25 patients with diabetes
      mellitus were studied. INTERVENTION: Patients with diabetes were examined by HRT
      and slit-lamp biomicroscopy with a contact lens. On HRT, the volumes above
      reference plane bound by three consecutive circles centered at the fovea
      (diameter, 1, 2, and 3 mm) were measured. Measurements were repeated three times
      in a masked fashion, and the mean measurements were used for the analysis. MAIN
      OUTCOME MEASURES: Visual acuity, macular edema, and volume above reference plane
      were measured. RESULTS: There were 19 diabetic eyes with clinical macular edema
      (deemed positives) and 13 without edema (deemed negatives). Diabetic eyes with
      macular edema had statistically greater volumes above reference plane than did
      diabetic eyes without edema (P < 0.001) and greater than the control eyes (P <
      0.001) for all three circles. There was no statistically significant difference
      between volumes measured in eyes without macular edema and control eyes (P = 0.42
      for the 1-mm diameter circle; P = 0.72 for the 2-mm diameter circle; and P = 0.19
      for the 3-mm diameter circle). For the two smallest circles only, the sensitivity
      of the HRT was 78.94%, and the specificity was 84.61%. None of the patients
      missed on the two smallest circles would have been positively identified on the 3
      mm diameter circle. CONCLUSION: The HRT can detect and quantify macular edema in
      diabetes by volumetric analysis with the method the authors have described. It is
      sufficient to measure the volumes above reference plane of two circles centered
      on the fovea and measuring 1 and 2 mm in diameter because the 3-mm diameter
      circle does not increase the system's sensitivity.

PMID- 9627657
TI  - Histologic localization of indocyanine green dye in aging primate and human
      ocular tissues with clinical angiographic correlation.
AB  - OBJECTIVE: This study aimed to histologically localize indocyanine green (ICG)
      dye in the geriatric primate and human eye and to correlate these findings with
      clinical ICG angiography. DESIGN: The study design was a clinicopathologic
      correlation. PARTICIPANTS: Six eyes of three geriatric monkeys (Maccaca mulatta)
      with macular drusen, 19 to 29 years of age, housed at the California Primate
      Research Center and an enucleated human eye from a 66-year-old patient with
      choroidal melanoma were examined. INTERVENTION: All six monkey eyes and the human
      eye underwent clinical ICG angiography. Five monkey eyes were enucleated at
      varying intervals after intravenous ICG dye injection for histologic examination.
      One monkey eye was removed without prior ICG injection as an age-matched control.
      The human eye was enucleated after intravenous injection of ICG dye. MAIN OUTCOME
      MEASURES: Infrared fluorescence microscopy of freeze-dried tissue sections was
      performed to detect ICG fluorescence. Histologic sections were stimulated with an
      810-nm diode laser, and the fluorescence emitted was detected with a Hamamatsu
      infrared camera. The images were digitally recorded. The distribution of
      fluorescence on histologic examination was correlated with the fluorescence of
      the clinical ICG angiogram. RESULTS: Infrared fluorescence microscopy of monkey
      sections localized fluorescence within retinal and choroidal vessels early after
      injection of ICG dye. The ICG fluorescence was seen in the extravascular
      choroidal stroma within 10 minutes after injection. The stromal fluorescence
      persisted in sections obtained 50 minutes after injection of ICG. The retinal
      pigment epithelium (RPE)-Bruch's membrane complex was brightly fluorescent in the
      middle- and late-stage histologic sections. Drusen deposits were brightly
      fluorescent at all timepoints examined. Similar findings were observed in freeze
      dried tissue sections of the human eye. The fluorescence detected on histologic
      sections correlated closely with the fluorescence of the clinical ICG angiograms
      for the same interval. CONCLUSIONS: The ICG dye does not remain solely within the
      choroidal intravascular space but extravasates into the choroidal stroma and
      accumulates within the RPE. Extravascular ICG binds to drusen material. These
      findings will enhance the interpretation of clinical ICG angiography.

PMID- 9627658
TI  - Patterns of visual field progression in patients with retinitis pigmentosa.
AB  - OBJECTIVE: The purpose of the study was to determine whether distinct patterns of
      visual field progression are present in patients with retinitis pigmentosa (RP)
      and to evaluate the correlation between these patterns, if present, and different
      genetic subtypes of RP. DESIGN: A retrospective analysis of patterns of visual
      field progression in RP was performed. PARTICIPANTS: Visual fields of 162
      patients with RP, including 55 with type 2 Usher syndrome, who had at least 3
      Goldmann visual field examinations during a period of at least 3 years were
      reviewed. MAIN OUTCOME MEASURES: Goldmann visual fields. RESULTS: Visual fields
      of 86 patients could be classified into one of three specific patterns of visual
      field progression. Pattern I included those patients with a progressive
      concentric loss of visual fields; pattern II included those with visual field
      loss that began superiorly and subsequently developed an arcuate scotoma that
      progressed either from the nasal (IIA) or the temporal (IIB and IIC) side; and
      pattern III included patients whose visual field loss was characterized initially
      by a complete or incomplete midperipheral "ring scotoma" that broke through into
      the periphery. The end stage of all these patterns was a residual central visual
      field, sometimes also associated with a small peripheral island. In 53 of the 162
      patients, the pattern of visual field loss could not be categorized because of an
      advanced stage of field loss at the time of the initial examination. CONCLUSIONS:
      Distinctive patterns of visual field progression can be observed in patients with
      retinitis pigmentosa and type 2 Usher syndrome. There were no intrafamilial
      variations in the pattern of visual field loss in our data on 24 patients from 11
      families. Within certain genetic subtypes, there was a predilection for a
      preponderance of a specific pattern of visual field progression. Future studies
      may be able to correlate these patterns of visual field loss with different
      genetic mutations. A greater understanding as to why certain patterns of field
      loss exist could potentially provide greater insight into the various
      pathogenetic mechanism(s) by which photoreceptor cells degenerate in this group
      of patients.

PMID- 9627659
TI  - Menkes disease. New ocular and electroretinographic findings.
AB  - OBJECTIVE: The authors describe new ocular and electroretinographic (ERG)
      features in Menkes disease. DESIGN: The study design is a case report.
      PARTICIPANTS: The authors studied two patients with Menkes disease. INTERVENTION:
      The authors performed complete ophthalmologic and ERG evaluations in both
      patients. MAIN OUTCOME MEASURES: The parameters used were slit-lamp biomicroscopy
      and ERG recordings. RESULTS: Aberrant lashes and anterior stromal hypoplasia of
      the iris are new findings, and profound delays in b-wave implicit time in well
      developed photopic responses may be added as new ERG features. CONCLUSIONS:
      Patients with Menkes disease may have aberrant lashes, anterior stromal
      hypoplasia, and retinal degeneration.

PMID- 9627660
TI  - Encapsulation of scleral buckling materials. A study of sixty specimens.
AB  - OBJECTIVE: The purpose of the study was to obtain information on the
      encapsulation of two nonabsorbable biomaterials (silicone and hydrogel) used as
      explants in scleral buckling in retinal detachment surgery. DESIGN: The study
      design was a histopathologic study on a cohort of capsule fractions and complete
      eyes. PARTICIPANTS: Fifty-nine patients participated in this study, in which 60
      specimens, including 37 hydrogel and 21 silicone capsule specimens as well as 2
      whole eyes, were gathered. There were no control subjects. INTERVENTION: The
      capsule specimens were obtained from eyes operated on previously for scleral
      buckling for retinal detachment. The two whole eyes were enucleated. All
      specimens were studied with routine optic microscopy. MAIN OUTCOME MEASURES:
      Patient characteristics, type of scleral buckling, and number of operations
      performed were analyzed. Histologically, the capsular structure, its interface
      with the explant, and its different components also were studied. Remnants of the
      buckling material also were investigated. RESULTS: There were 45 male and 14
      female patients, with a mean age of 49 years. Histologically, capsule specimens
      had a fibrous matrix with fibroblasts and few inflammatory cells. Eighteen
      (48.6%) of 37 hydrogel capsule specimens displayed hydrogel fragments surrounded
      by a foreign body giant cell granuloma in 16 cases. CONCLUSION: Nonabsorbable
      materials undergo encapsulation after implantation on the eye surface. Giant cell
      granuloma was observed in some hydrogel capsule specimens in relation to hydrogel
      fragmentation. The exact origin of this fragmentation remains unknown.

PMID- 9627661
TI  - Incidence of surgically treated uveal melanoma by race and ethnicity.
AB  - OBJECTIVE: The purpose of the study was to determine the race- and ethnicity
      specific incidence of histologically confirmed uveal melanoma. DESIGN: The study
      design was a retrospective study of histologically confirmed cases of primary
      uveal melanoma submitted to the Florida Cancer Data System (FCDS). MAIN OUTCOME
      MEASURES: Race-, gender-, and Hispanic-specific incidence rates of uveal melanoma
      were measured. Calculations are based on Florida census data and Hispanic
      population estimates from the University of Florida Bureau of Economic and
      Business Research. RESULTS: From 1981 through 1993, 873 histologically confirmed
      uveal melanomas were reported to the FCDS. Four melanomas occurred in black non
      Hispanics, 47 in white Hispanics, and none in black Hispanics. The relative risk
      of uveal melanoma for blacks compared to non-Hispanic whites was 0.03 (95%
      confidence interval, 0.01-0.08). Non-Hispanic white men had 72 times the risk of
      uveal melanoma compared to black men; non-Hispanic white women experienced a 22
      fold risk compared to black women. White Hispanics were less likely to develop
      uveal melanoma than white non-Hispanics (relative risk, 0.36; 95% confidence
      interval, 0.27-0.48). CONCLUSION: The risk of uveal melanoma in blacks is
      exceptionally low. The reason for lower risk of uveal melanoma in white Hispanics
      than in white non-Hispanics is not known but could be related to the protective
      effects associated with dark skin pigmentation or may be because of unknown
      cultural-environmental exposures or socioeconomic factors.

PMID- 9627662
TI  - Cavitary melanoma of the ciliary body. A study of eight cases.
AB  - PURPOSE: The authors present the unique clinical features of cavitary uveal
      melanoma. DESIGN: Retrospective chart review. PARTICIPANTS: Eight patients with
      cavitary uveal melanoma. MAIN OUTCOME MEASURES: The clinical, ultrasonographic,
      and histopathologic features of eight patients with cavitary melanoma of the
      ciliary body were studied. RESULTS: In all eyes there was a brown ciliary body
      mass that blocked transmission of light on trans-scleral transillumination.
      Ocular ultrasonography revealed a large, single hollow cavity (unilocular
      "pseudocyst") in five cases and multiple hollow cavities (multilocular
      "pseudocyst") in three cases. The cavity occupied a mean of 55% of the entire
      mass thickness (range, 31%-79%). In five cases, a basal uveal mass was noted on
      ultrasonography. Four patients underwent tumor resection; one had enucleation,
      and three had 125I radioactive plaque treatment. In the five cases confirmed
      histopathologically, the cavitation was empty, contained erythrocytes, serous
      fluid, and/or pigment-laden macrophages. In no case was the cavity lined by
      necrotic tumor, endothelial cells, or epithelial cells. CONCLUSION: Ciliary body
      melanoma can develop an intralesional cavity resembling an intraocular cyst. The
      presence of a solid mass at the base and a thick wall surrounding the cavity can
      assist in the differentiation of cavitary melanoma from benign cyst.

PMID- 9627663
TI  - Ocular abnormalities in the mucopolysaccharidoses after bone marrow
      transplantation. Longer follow-up.
AB  - OBJECTIVE: The purpose of the study was to provide longer follow-up of ocular
      findings in patients with mucopolysaccharidoses (MPS) after bone marrow
      transplantation (BMT). DESIGN: The study design was a retrospective 6-year cohort
      evaluation. PARTICIPANTS: Twenty-three patients with MPS (19 with MPS type I-H, 3
      with MPS type III, 1 with MPS type VI) were studied. INTERVENTION: Bone marrow
      transplantation was performed. MAIN OUTCOME MEASURES: The following outcome
      measures were considered: vision, slit-lamp biomicroscopic and funduscopic
      examinations, intraocular pressure, electroretinography (ERG), and retinoscopy.
      RESULTS: Thirteen (81%) of 16 patients showed ERG improvement in the first year.
      However, all patients showed slowly progressive decline of the ERG over longer
      follow-up. Other ocular findings included optic atrophy (n = 7 patients), disc
      edema (n = 6 patients), strabismus (n = 6 patients), nystagmus (n = 6 patients),
      cataract (n = 3 eyes), keratoconjunctivitis sicca (n = 4 eyes), ocular
      hypertension (n = 2 eyes), and glaucoma (n = 2 eyes). CONCLUSIONS: The MPS are
      rare and heterogeneous disorders characterized by progressive retinal
      degeneration and blindness. Ocular abnormalities can occur as a result of the
      disease or as a consequence of BMT. Successful BMT has been shown to improve
      systemic health, but this may not reflect continuing ocular status and retinal
      function. Despite early improvement in ERG function, longer follow-up suggests
      progressive retinal decline.

PMID- 9627664
TI  - Prospective randomized comparison of external dacryocystorhinostomy and endonasal
      laser dacryocystorhinostomy.
AB  - OBJECTIVE AND DESIGN: The introduction of endonasal laser dacryocystorhinostomy
      (ENL-DCR) in the early 1990s showed great promise of changing
      dacryocystorhinostomy into an elegant, minimally invasive procedure from the
      traditional external dacryocystorhinostomy (EXT-DCR). This prospective,
      randomized study compares these two operations, their success rates, surgical
      durations, and postoperative symptoms. PARTICIPANTS: A total of 64 cases in 61
      patients with primary acquired nasolacrimal sac or duct obstruction were divided
      into 2 subgroups by symptoms (simple epiphora and chronic dacryocystitis). These
      patients were randomized within both subgroups into 2 operation groups with 32
      cases in each group. INTERVENTION: Altogether, 32 EXT-DCRs and 32 ENL-DCRs were
      performed. The silicone tube was removed at 6 months after surgery. The final
      follow-up visit was at 1 year after surgery. The patency of the lacrimal passage
      was investigated by irrigation, and patients were questioned about their
      symptoms. MAIN OUTCOME MEASURES: The patency of the lacrimal passage to
      irrigation and the duration of surgery were measured. RESULTS: The success rate
      at 1 year after surgery was 91% for EXT-DCR and 63% for ENL-DCR after primary
      surgery. The difference was statistically significant (P = 0.016). The surgical
      duration for ENL-DCR was three times shorter than for EXT-DCR, the average
      duration being 23 minutes and 78 minutes, respectively (P < 0.0001). CONCLUSIONS:
      The EXT-DCR, when compared with ENL-DCR, seems to provide superior operation
      results in primary acquired nasolacrimal duct obstruction.

PMID- 9627665
TI  - The epidemiology of dry eye in Melbourne, Australia.
AB  - OBJECTIVE: To describe the epidemiology of dry eye in the adult population of
      Melbourne, Australia. DESIGN: A cross-sectional prevalence study. PARTICIPANTS:
      Participants were recruited by a household census from two of nine clusters of
      the Melbourne Visual Impairment Project, a population-based study of age-related
      eye disease in the 40 and older age group of Melbourne, Australia. Nine hundred
      and twenty-six (82.3% of eligible) people participated; 433 (46.8%) were male.
      They ranged in age from 40 to 97 years, with a mean of 59.2 years. MAIN OUTCOME
      MEASURES: Self-reported symptoms of dry eye were elicited by an interviewer
      administered questionnaire. Four objective assessments of dry eye were made:
      Schirmer's test, tear film breakup time, rose bengal staining, and fluorescein
      corneal staining. A standardized clinical slit-lamp examination was performed on
      all participants. Dry eye for the individual signs or symptoms was defined as:
      rose bengal > 3, Schirmers < 8, tear film breakup time < 8, > 1/3 fluorescein
      staining, and severe symptoms (3 on a scale of 0 to 3). RESULTS: Dry eye was
      diagnosed as follows: 10.8% by rose bengal, 16.3% by Schirmer's test, 8.6% by
      tear film breakup time, 1.5% by fluorescein staining, 7.4% with two or more
      signs, and 5.5% with any severe symptom not attributed to hay fever. Women were
      more likely to report severe symptoms of dry eye (odds ratio [OR] = 1.85; 95%
      confidence limits [CL] = 1.01, 3.41). Risk factors for two or more signs of dry
      eye include age (OR = 1.04; 95% CL = 1.01, 1.06), and self-report of arthritis
      (OR = 3.27; 95% CL = 1.74, 6.17). These results were not changed after excluding
      the 21 people (2.27%) who wore contact lenses. CONCLUSIONS: These are the first
      reported population-based data of dry eye in Australia. The prevalence of dry eye
      varies by sign and symptom.

PMID- 9627666
TI  - Conjunctival flaps.
AB  - PURPOSE: The authors reviewed their experience with total conjunctival flaps
      (TCF) and partial conjunctival flaps (PCF) for the past 5 years in 61 patients.
      METHODS: Forty-eight patients had TCF and 13 had PCF. Diagnoses for surgery
      included severe bullous keratopathy for chronic graft failure (not candidates for
      keratoplasty) (19), herpes zoster ophthalmicus (7), chronic ulcerative keratitis
      (14), neurotrophic keratitis (2), and herpes simplex keratitis (9). RESULTS:
      There were seven complications. Four flap retractions occurred in the TCF group,
      requiring resuturing in two. Three complications occurred in the PCF group. One
      patient had two flap retractions and recurrent ulceration, requiring
      tarsorrhaphy. One patient with PCF suffered a perforation after flap retraction,
      necessitating penetrating keratoplasty. CONCLUSION: The authors believe
      conjunctival flaps are underused and should be considered seriously for bullous
      keratopathy, neurotrophic keratitis, recalcitrant keratitis, and persistent
      nonhealing epithelial defects.

PMID- 9627667
TI  - Antineoplastic agents 365. Dolastatin 10 SAR probes.
AB  - The remarkable anticancer drug dolastatin 10 (1a) from the Indian Ocean sea hare
      Dolabella auricularia is currently undergoing phase I clinical trials. Thirty
      eight new structural modifications of this unusual peptide have been synthesized
      and evaluated against a variety of human and murine cancer cell lines, and for
      their ability to inhibit tubulin polymerization and vinblastine and GTP binding
      to tubulin. Dolastatin 10 and one structural modification was found to have
      antifungal activity, while one other structural modification of the parent
      compound exhibited antibacterial activity. Some of the new peptides approximated
      the antineoplastic potency of dolastatin 10, especially those based on
      replacement of the Doe unit with Met, Phe or an appropriately substituted
      phenylethylamide.

PMID- 9627668
TI  - Uptake of a boronated epidermal growth factor-dextran conjugate in CHO xenografts
      with and without human EGF-receptor expression.
AB  - An epidermal growth factor (EGF)-dextran-boron conjugate for targeting against
      EGF receptor-rich tumours was investigated regarding uptake and distribution in
      vivo. EGF served as the tumour-seeking part and dextran was the carrier for the
      potentially toxic boron. Nude mice carrying subcutaneous tumours on the flanks
      were injected with conjugate either i.v. or intratumorally. The xenografts were
      from Chinese hamster ovary cells transfected with the gene for the human EGF
      receptor (CHO-EGFR), and these cells expressed the EGFR. Non-transfected cells
      without EGF-receptors (CHO) were used as controls. No accumulations in tumours
      could be observed following the i.v. injections but there were, in both tumour
      types, high accumulations in the liver. Following intratumoral injections the
      accumulations were higher in the CHO-EGFR tumours than in the CHO tumours. The
      tumour over blood and liver ratios were also higher for the CHO-EGFR tumours than
      for the CHO tumours. Thyroid accumulations after the intratumoral injections
      indicate different degradation patterns of the conjugate in CHO-EGFR animals than
      in CHO animals. In conclusion, after intratumoral injections the conjugate showed
      receptor-dependent binding to EGFR-rich tumours, and the tumour-to-blood and
      tumour-to-liver ratios were promising.

PMID- 9627669
TI  - Toxicity of liposomal 3'-5'-O-dipalmitoyl-5-fluoro-2'-deoxyuridine in mice.
AB  - Toxicities of 5-fluoro-2'-deoxyuridine (FUdR) and its liposome incorporated
      dipalmitoyl derivative (FUdR-dipalmitate) to mouse bone marrow, spleen, liver and
      ileum were compared after treatment for 6 consecutive days. The applied doses of
      the two formulations, which were shown earlier to have equal antitumor activity
      in mouse tumor models, were 600 and 2 mumol/kg respectively. When applied in
      these doses, toxicity to the hemopoietic system, measured as a decreases in
      progenitor and precursor cells of the erythroid and granuloid/macrophage lineage
      in bone marrow and spleen, was more severe for FUdR than for liposomal FUdR
      dipalmitate. In the liver, mitotic figures, as indicators of cell division, were
      absent for both drugs while in control livers the number of cells in mitosis was
      approximately 2%. Toxicity to the ileum was more severe for liposomal FUdR
      dipalmitate than for FUdR and was manifested by granulocyte infiltration, the
      presence of cell debris, loss of columnar epithelial cells and enlarged nuclei
      with prominent nucleoli in these cells. Thus, by prolonging the retention time of
      FUdR in vivo, using liposomes as a vehicle and FUdR-dipalmitate as a lipophilic
      prodrug, the dose-limiting toxicity appears to shift from bone marrow to the
      gastrointestinal tract.

PMID- 9627670
TI  - Comparison of ternary crystal complexes of F31 variants of human dihydrofolate
      reductase with NADPH and a classical antitumor furopyrimidine.
AB  - The novel furopyrimidine, N-[4-[(2,4-diaminofuro[2,3-d]pyrimidin-5-yl)-methyl]
      methylamino] -benzoyl]-L-glutamate (MTXO), a classical antifolate with weak
      antitumor activity compared with methotrexate (MTX), has been studied as
      inhibitorcofactor ternary crystal complexes with recombinant Phe-31 to Ser (F31S)
      and Phe-31 to Gly (F31G) variant human dihydrofolate reductase (hDHFR). Kinetic
      data show that the binding affinity of MTXO is significantly weaker for the
      variant hDHFR enzyme than for the wild type enzyme. Structural data for the Phe
      31 variants, along with wild type hDHFR, provide the first direct comparison of
      the binding interactions of a single antifolate in a family of variant hDHFR.
      These ternary hDHFR complexes crystallize in the rhombohedral space group R3,
      isomorphous to that reported for wild type hDHFR MTXO-NADPH ternary complex. MTXO
      binds with its 2,4-diaminofuropyrimidine ring interacting with Glu-30 in hDHFR.
      The greatest change on modification of the side chain at position 31 is loss of
      hydrophobic contacts to the inhibitor, which results in the significant decrease
      in binding affinity of MTXO for the Phe-31 variants. The presence of the 6-5
      furopyrimidine ring instead of the 6-6 pteridine ring causes a different bridge
      conformation compared with MTX, and in the case of the wild type MTXO complex
      also results in weaker hydrophobic contacts to Phe-31 than observed for MTXT. For
      the design of antitumor agents related to MTXO, increasing the bridge of MTXO
      from two to three or four atoms should provide increased DHFR inhibitory potency
      and antitumor activity.

PMID- 9627671
TI  - Requirements for P-glycoprotein recognition based on structure-activity
      relationships in the podophyllotoxin series.
AB  - Podophyllotoxin and epipodophyllotoxin react with tubulin at the same binding
      site as colchicine, but in contrast to colchicine, do not appear to exert their
      cytotoxicities by mechanisms dependent on P-glycoprotein (Pgp) expression. To
      investigate structural requirements for Pgp recognition a series of
      podophyllotoxin and epipodophyllotoxin derivatives have been synthesized. Their
      interactions with the multidrug resistance-related protein Pgp have been studied
      by evaluating their relative cytotoxicities versus P388-sensitive murine leukemic
      cells and a classic multidrug-resistant (MDR) Pgp-overexpressing subline
      (P388/ADR), and their relative tubulin polymerization inhibitory activities
      against microtubular proteins have been determined. Based on tridimensional
      structure-activity relationships within this series of compounds, structural
      requirements for Pgp recognition have been identified. Moreover, proposals are
      made for extending these criteria to other chemical classes of anticancer drugs.

PMID- 9627672
TI  - Synthesis, DNA-binding properties and cytotoxic activity of flavin
      oligopyrrolecarboxamide and flavin-oligoimidazolecarboxamide conjugates.
AB  - The aim of this study was to develop novel series of photosensitizer-DNA minor
      groove binder hybrids composed of a flavin (isoalloxazine) chromophore linked to
      a moiety related to netropsin or distamycin. Three series (Fla-Pyr, Fla-Gly-Pyr
      and Fla-Gly-Im) were synthesized which differ by the number and the nature of the
      heterocyclic nuclei in the oligopeptide units, the nature of the linker and its
      anchoring position on the flavin. In terms of DNA binding and DNA specificity,
      satisfactory data are obtained in the Fla-Pyr and Fla-Gly-Pyr series; in terms of
      photo-induced cytotoxicity, the results are disappointing. The present study
      allows us to draw the following structure-activity relationships: (i)
      substitution of the flavin nucleus in either the N3 or the N10 position does not
      affect the activity; (ii) tris-pyrrolic hybrids are more efficient than bis- and
      tetra-pyrrolic analogs; (iii) the presence of a glycin in the linking chain does
      not suppress the DNA binding properties or the cytotoxic activities of the
      hybrids; and (iv) the replacement of the pyrrole nuclei by imidazoles has a
      drastic effect since it results in the loss of DNA affinity and cytotoxicity.

PMID- 9627673
TI  - 1-Amino-substituted 8-hydroxy-4,5-dimethyl-5H-pyrido[4,3-b]indoles with propyl-
      or methyl substituents at the 9-, and 7,9-positions: synthesis and biological
      evaluation.
AB  - The title compounds were synthesized in 9-10 steps in order to compare their
      cytotoxic properties to that for 1-(3-dimethylaminopropyl)-amino-4,5-dimethyl- 8
      hydroxy-5H-pyrido[4,3-b]indole. Whereas the latter is a potent cytotoxic agent,
      displaying significant antitumour activity, the corresponding 9-propyl (and 7,9
      dimethyl) derivatives were found to be > 10-fold less cytotoxic.

PMID- 9627674
TI  - Synthesis, properties and biological evaluation of substituted furo[3,2-e] and
      pyrano[3,2-e]pyrido[4,3-b]indoles.
AB  - Furo[3,2-e]- and pyrano[3,2-e]pyrido[4,3-b] indoles were synthesized from 1,4,5
      trisubstituted 8-hydroxy-5H-pyrido[4,3-b]indoles. The intermediates, 10-chloro-6H
      furo[3,2-e]pyrido[4,3-b]indole (11), 10-chloro-2,6-dihydro-1H-furo[3,2-e]pyrido
      [4,3-b]indole (10) and 11-chloro-2,3-dihydro-3H,7H-pyrano[3,2-e]pyrido[4,3
      b]indole (15), were substituted by diamines under thermal conditions (180 degrees
      C). In contrast, 11-chloro-3H,7H-pyrano[3,2-e]pyrido[4,3-b]indole (14), 9-allyl-1
      chloro-4,5-dimethyl-5H-pyrido[4,3-b]indole (9a) and 8-propargyloxy-4,5-dimethyl
      5H-pyrido[4,3-b]indole (8) led mainly to 1-aminosubstituted 8-hydroxy-5H
      pyrido[4,3-b]indole derivatives resulting from an unexpected C3 unit elimination.
      When examined in three tumour cell lines (L1210 leukaemia, the B16 melanoma and
      the MCF7 breast adenocarcinoma) the new amino substituted furo[3,2-e]-,
      dihydrofuro[3,2-e]- and dihydropyrano[3,2-e]-pyrido[4,3-b]indole derivatives
      revealed cytotoxic properties, especially important for the 2,6-dihydro-1H
      furo[3,2-e]pyrido[4,3-b]indole series. The most active compound (12b)
      significantly inhibits both DNA topoisomerases I and II, and is as potent as
      Adriamycin at inhibiting cell proliferation and inducing a massive accumulation
      of L1210 cells in the G2 + M phase of the cell cycle. However, 12b was less
      active than Adriamycin when tested in vivo against P388 leukaemia or the B16
      melanoma tumour models.

PMID- 9627675
TI  - Treatment of advanced refractory sarcomas with ifosfamide and etoposide
      combination chemotherapy.
AB  - Chemotherapy options for resistant advanced-stage sarcomas are limited and in
      most cases disappointing. In a phase II study, we treated 26 consecutive patients
      with refractory advanced sarcoma with ifosfamide and etoposide combination
      chemotherapy. All patients had received prior doxorubicin- and/or
      cyclophosphamide-based chemotherapies. Seventeen patients were male and 9 were
      female. The patients' median age was 35 years (range: 19-67 years). A total of 24
      patients were eligible for evaluation of responses. Seven patients had a complete
      response (CR) (29.1%), 3 had a partial response (PR) (12.5%), 3 had stable
      disease (SD) (12.5%), and 11 had progressive disease (PD) (45.9%). An overall
      41.6% objective response was achieved. Median time to treatment failure was 13.3
      months. A total of 108 cycles of therapy were evaluable for evaluation of
      toxicity. Myelosuppression, observed in 55.5% of the treatment courses, was the
      major dose-limiting toxicity. Nausea and vomiting, seen in 64% of the courses,
      were the most important nonhematological side effects. Alopecia was almost
      universal. Hemorrhagic cystitis was observed in only 1 patient. We have concluded
      that the combination of ifosfamide, mesna, and etoposide is effective in advanced
      refractory sarcomas, and has acceptable toxicity.

PMID- 9627676
TI  - In vitro screening model for the detection of agents active against myelogenous
      leukemia.
AB  - This study was directed at defining the optimal in vitro screening methodology
      for the selection of new anti-myelogenous leukemia agents. Using thousands of
      samples of synthetic compounds from the Eastman Pharmaceutical, Inc. and Sterling
      Research Corporation (Eastman/Sterling) inventory, a number of sequential
      combinations of 8 cell lines were employed to optimize the model. The cells in
      these lines were of either murine (L1210 lymphocytic leukemia, C1498 myelogenous
      leukemia, and colony-forming unit-granulocyte macrophage [CFU-GM]) or human (HL
      60, K-562, HEL, and THP-1 myelogenous leukemias, and CFU-GM) origin. The focus of
      the study was to find the most efficient and cost-effective manner in which to
      test compounds for both cytotoxicity against the tumor cells and for differential
      cytotoxicity against tumor as compared with normal cells.

PMID- 9627677
TI  - Ki-1 anaplastic large-cell lymphoma in the differential diagnosis of unknown
      primary cancer.
AB  - The importance of immunohistochemical analysis of anaplastic or undifferentiated
      carcinoma, especially in the setting of an unusual clinical presentation, is
      illustrated by two cases of metastatic undifferentiated carcinoma. Re-evaluation
      of pathological material resulted in a diagnosis of Ki-1 lymphoma and led to
      substantial alteration in therapeutic strategy and long-term outlook. The
      response to therapy was unusually favorable in both cases, and survival was
      prolonged in both. Archival pathological material was retrieved in order to
      perform special studies that were not originally available at the time of
      diagnosis, consisting of immunoperoxidase detection of hematological markers that
      are preserved in formalin-fixed, paraffin-embedded tissues. Both tumors were
      found in retrospect to actually represent anaplastic, Ki-1-positive, large-cell
      lymphoma. This neoplastic entity has been introduced to the oncologic literature
      only within the past decade. Because this neoplasm shows chemosensitivity and
      responsiveness similar to that of other large-cell lymphomas, we alert
      practitioners to consider this diagnosis in any patient who presents with an
      apparently metastatic undifferentiated tumor.

PMID- 9627678
TI  - Phase II trial of docetaxel (Taxotere) for untreated advanced colorectal
      carcinoma.
AB  - The antimicrotubule agent docetaxel (Taxotere), a semisynthetic taxoid, has
      demonstrated antitumor activity against colorectal cancer cell lines in vitro,
      and in murine tumor models. We sought to characterize its activity in a group of
      previously untreated patients with colorectal carcinoma. Eighteen previously
      untreated patients with advanced, measurable colorectal carcinoma were treated
      with a 60-min intravenous infusion of docetaxel with a dose of 100 mg/m2
      administered every 21 days. Routine premedication with diphenhydramine was given.
      Patients were required to have normal organ function and a Karnofsky performance
      status (KPS) > or = 60%. No complete response (CR) or partial responses (PR) were
      observed. Median survival was 13 months, despite a median time to progression of
      only 1.3 months. Neutropenia was the most common dose-limiting toxicity,
      resulting in 5 episodes of febrile neutropenia requiring hospitalization and
      intravenous antibiotics. One patient experienced a grade 4 hypersensitivity
      reaction (HSR) requiring treatment termination. No toxic deaths occurred. Despite
      encouraging preclinical data, docetaxel is an inactive drug in advanced
      colorectal cancer when given in the dose and on the schedule examined in the
      present study, and has significant, although reversible, toxicities.

PMID- 9627679
TI  - Thrombosis of the internal jugular vein: a rare manifestation of the
      hypercoagulability of malignancy.

PMID- 9627680
TI  - The involvement of selectins in cell adhesion, tumor progression, and metastasis.

PMID- 9627681
TI  - The role of integrins in tumorigenesis and metastasis.

PMID- 9627682
TI  - General principles of antibiotic therapy.

PMID- 9627683
TI  - Clinical cancer research in a managed-care environment.

PMID- 9627684
TI  - Clinical uses for calciotropic hormones 1,25-dihydroxyvitamin D3 and parathyroid
      hormone-related peptide in dermatology: a new perspective.
AB  - The skin is not only the organ for the photosynthesis of vitamin D3, but also a
      target tissue for its activated form 1,25-dihydroxyvitamin D3 (1,25(OH)2D3).
      Vitamin D3 is absolutely essential for the development and maintenance of a
      healthy skeleton. Without an adequate source of vitamin D, children develop
      rickets and the elderly develop osteomalacia and exacerbation of osteoporosis.
      1,25(OH)2D3 is a potent inhibitor of proliferation of epidermal cells and, with
      its analogs, it has been developed for the successful treatment of psoriasis. Not
      all psoriasis patients, however, respond to 1,25(OH)2D3 and its analogs. Evidence
      suggests that there may be a defect in the regulation of levels of mRNA for the
      vitamin D receptor in patients who have partial or no response to 1,25(OH)2D3
      therapy. The degree of responsiveness to 1,25(OH)2D3 therapy may also be related
      to the allelic variations in the vitamin D receptor gene. Parathyroid hormone
      related peptide is synthesized by the epidermis and is an endogenous
      antiproliferative factor. Parathyroid hormone-related peptide agonists and
      1,25(OH)2D3 inhibit in vitro and in vivo epidermal proliferation, whereas
      parathyroid hormone-related peptide antagonists stimulate both epidermal
      proliferation and hair growth in vivo. Therefore, the calciotropic hormones
      1,25(OH)2D3 and parathyroid hormone-related peptide have wide-ranging clinical
      applications in dermatology.

PMID- 9627685
TI  - The concept of multiple vitamin D signaling pathways.
AB  - Nuclear signaling by 1 alpha, 25-dihydroxyvitamin D3 (VD) is mediated by its
      nuclear receptor (VDR). It is widely accepted that VDR forms heterodimers with
      retinoid X receptors (RXRs) that bind in 5'-RXR-VDR-3' polarity to response
      elements formed by direct repeats of hexameric core binding motifs spaced by
      three nucleotides. This model, however, might be too simple to explain the
      multiplicity of nuclear signaling by VD. Recently, it was reported that VDR forms
      homodimers and heterodimers with the nuclear receptors for all-trans retinoic
      acid and thyroid hormone. All four different VDR complexes bind not only to
      direct repeats, but also to inverted palindromes; moreover, in heterodimeric
      complexes VDR can also take the 5' position. Taken together, this discriminates
      at least seven different types of VDR complexes binding each to two types of
      response elements. For half of these 14 cases, representative natural VD response
      elements have already been identified, which demonstrates that nature takes
      advantage of this concept of diversity. It is our hypothesis that the different
      physiological functions of VD can be related to different VD signaling pathways.
      Therefore, the identification of VD analogs that specifically trigger these
      pathways is the goal of our present and future investigations.

PMID- 9627686
TI  - Pharmacology and molecular action of retinoids and vitamin D in skin.
AB  - All-trans retinoic acid and 1,25-dihydroxyvitamin D3 are biologically active
      hormones derived from metabolism of vitamins A and D, respectively. Their
      cellular effects in physiology and pharmacology are mediated mainly through their
      nuclear receptors, retinoic acid receptors (RARs), and vitamin D receptor (VDR),
      which are members of the steroid/thyroid hormone receptor superfamily. The
      nuclear receptor superfamily is a group of hormone (ligand)-dependent
      transcription factors that bind to specific DNA recognition sequences located in
      the promotor region of target genes and modulate the gene transcription. Both
      RARs and VDR bind to DNA in the form of heterodimers with retinoid X receptor
      (RXR) as the key partner. In human skin epidermis, endogenous RAR and VDR bind to
      their respective enhancer elements as heterodimers (RAR-RXR, VDR-RXR) and not as
      homodimers. 9-cis retinoic acid is the natural ligand for RXRs. Because RXR
      heterodimerizes with either RARs or VDR, it functions as a key protein in the
      overall retinoid or vitamin D response of a given biological system. The
      contribution of RXRs in coregulating these signaling pathways is likely to depend
      on the abundance of the RXRs within target cells, the relative amounts of other
      receptors with which they can dimerize, and the availability of their ligands
      (hormones). Understanding each of these components in human skin in vivo will
      lead to practical applications in dermatologic therapeutics.

PMID- 9627687
TI  - 1,25(OH)2D3-modulated calcium induced keratinocyte differentiation.
AB  - Keratinocytes produce vitamin D3, metabolize it to its most biologically active
      form, 1,25-dihydroxyvitamin D3 (1,25[OH]2D3), and respond to the 1,25(OH)2D3 they
      produce with a decrease in proliferation and an increase in differentiation.
      1,25(OH)2D3 production by keratinocytes is tightly controlled and changes as the
      cells differentiate, increasing during the early stages of differentiation, then
      decreasing again as terminal differentiation ensues. The 1,25(OH)2D3 produced
      endogenously or supplied exogenously acts in concert with calcium to stimulate
      the transition from a proliferating basal cell to a terminally differentiated
      corneocyte. The mRNA levels for proteins involved in the differentiation process
      are controlled not only by calcium- and 1,25(OH)2D3-induced increase in gene
      transcription, but by subsequent calcium- and 1,25(OH)2D3-induced destabilization
      of the mRNA after adequate levels of the proteins have been produced. 1,25(OH)2D3
      increases intracellular calcium in part by inducing phospholipase C, which when
      activated by hormones, cleaves phosphoinositol bisphosphate into two important
      signaling molecules inositol tris phosphate and diacylglycerol. Inositol tris
      phosphate releases intracellular calcium from intracellular stores, and the
      increase in intracellular calcium opens up the nonspecific cation channel through
      which calcium enters the cell. Diacylglycerol and intracellular calcium promote
      protein kinase C activity that can further enhance the differentiation process.
      These actions of 1,25(OH)2D3 provide the rationale for the effectiveness of
      1,25(OH)2D3 and its analogs in psoriasis.

PMID- 9627688
TI  - Normal levels of the vitamin D receptor and its message in psoriatic skin.
AB  - Treatment with vitamin D3 analogs improves psoriasis. The vitamin D receptor
      (VDR) mediates most, if not all, the effects of vitamin D3. The purpose of this
      study was to determine the levels of the VDR mRNA and VDR protein in normal and
      in involved and uninvolved psoriatic skin. Although VDR mRNA was not detected by
      Northern analysis of human skin samples, it was readily detectable by use of the
      more sensitive ribonuclease protection assay. The VDR mRNA levels were normal in
      acute guttate as well as in chronic plaque lesions. There was also no difference
      in VDR mRNA levels between normal and uninvolved psoriatic skin. The VDR protein
      was detected by Western analysis using the monoclonal 9A7 gamma anti-VDR antibody
      and a polyclonal rabbit anti-VDR antibody. For comparison, VDR levels were
      analyzed in cultures of normal human keratinocytes and the epithelial cell line
      MCF-7. Studies of the extraction procedures for VDR showed that at least 60% of
      Escherichia coli-expressed VDR added to the skin biopsy specimens was recovered.
      The VDR concentration in normal human adult skin was approximately 50
      pg/microgram protein, and the concentrations of VDR in involved and uninvolved
      psoriatic skin were of the same order of magnitude. Using the 9A7 gamma anti-VDR
      antibody, the VDR (M(r) 53,000) was constantly present in lower amounts than a
      band of M(r) 80,000 in both skin specimens and keratinocyte cultures. This high
      molecular-weight band is most likely a cross-reacting protein not related to VDR,
      because it was absent when using the polyclonal anti-VDR antibody.

PMID- 9627689
TI  - Vitamin D3 regulation of transforming growth factor-beta system in epithelial and
      fibroblastic cells--relationships to plasminogen activation.
AB  - Vitamin D3 and its analogs are potent regulators of growth and differentiation of
      various cell types. A mechanism of action of vitamin D3 and other steroid
      hormones is to enhance the secretion of transforming growth factor-beta (TGF
      beta) in target cells. In epidermal keratinocytes, vitamin D3 induced the
      expression of both TGF-beta 1 and TGF-beta 2 with minor changes in mRNA levels,
      while in BT-20 breast carcinoma cells the increase in TGF-beta activity was
      preceded by an induction of mRNA. In both cell systems, the absolute amounts of
      active TGF-beta increased, and in keratinocytes the proportion of active TGF-beta
      was also enhanced. A concomitant enhancement of secretion of the latent TGF-beta
      binding protein by vitamin D3 was observed in BT-20 cells. Retinoic acid, which
      is known to interfere with vitamin D3 signaling, slightly decreased the levels of
      secreted TGF-beta 1 protein in BT-20 cells, but did not significantly affect the
      vitamin D3-induced increase. In addition to regulation of the TGF-beta system,
      vitamin D3 decreases pericellular plasminogen activator activity in
      keratinocytes. Plasmin-mediated proteolytic events are involved in the release
      from pericellular space and activation of TGF-beta. We analyzed vitamin D3
      regulation of fibroblast growth and the secretion of PA activity. Vitamin D3
      inhibited fibroblast growth in a concentration-dependent manner and downregulated
      plasminogen activator activity as in keratinocytes. In fibroblasts, vitamin D3
      did not induce notable alterations in TGF-beta 1 or latent TGF-beta-binding
      protein secretion, suggesting divergent growth inhibitory mechanisms. Our results
      indicate that vitamin D3 and its analogs are potent regulators of the TGF-beta
      and plasminogen activator systems in cells of epithelial and mesenchymal origin.

PMID- 9627690
TI  - Synergy between vitamin D precursor 25-hydroxyvitamin D and short chain ceramides
      on keratinocyte proliferation and differentiation.
AB  - The active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (1,25D), and its
      analogs induce normal human keratinocyte differentiation and are used for the
      treatment of psoriasis. Long-term topical use of 1,25D, however, causes
      hypercalcemia. The precursor of 1,25D, 25-hydroxyvitamin D3 (25D) is converted to
      1,25D in the keratinocyte in a regulated manner. The action of 1,25D is reported
      to be mediated, at least in part, by cellular ceramides in the leukemia cell
      line, HL-60 cells. Therefore, in this study we evaluated the synergy between 25D
      and short chain cell permeable ceramides (SCC) or synthetic analogs of ceramides
      on keratinocyte growth and differentiation in vitro. C2 ceramide (acetyl
      sphingosine) synergistically enhanced the growth inhibitory effect of 25D and
      1,25D in a concentration-dependent manner. Short chain analogs of ceramide-like
      compounds, neoceramides and pseudoceramides, also inhibited keratinocyte
      proliferation and acted in synergy with 25D and 1,25D. SCC alone increased
      transglutaminase and cornified envelope levels. 25D potentiated this
      prodifferentiating effect of SCC. Twenty-four-hour preincubation with SCC did not
      alter 25D or 1,25D uptake into keratinocytes. These studies demonstrate a synergy
      between vitamin D metabolites and ceramides in human keratinocytes and indicate
      the potential of using 25D as an effective and safer alternative to deliver 1,25D
      benefits to the epidermis.

PMID- 9627691
TI  - The anti-proliferative and differentiation-inducing effects of vitamin D analogs
      are not determined by the binding affinity for the vitamin D receptor alone.
AB  - Calcipotriol, a synthetic analog of 1 alpha,25-dihydroxyvitamin D3 (1
      alpha,25[OH]2D3), is used in the treatment of psoriasis. In this investigation,
      the biological profile of calcipotriol and of two new vitamin D analogs, EB 1213
      and GS 1500, has been studied and compared with the profile of 1 alpha,25(OH)2D3.
      Despite the fact that the affinity for the intracellular vitamin D receptor of
      the three analogs is comparable (EB 1213) or lower (GS 1500, calcipotriol) than
      that of 1 alpha,25(OH)2D3, they were all found to be more potent in inhibiting
      human skin cell proliferation in vitro. The anti-proliferative effect was
      accompanied by a change in the cytokeratin pattern of the skin cells, indicating
      a differentiation-inducing effect of the compounds similar to that of 1
      alpha,25(OH)2D3. Further investigations including ligand-induced vitamin D
      receptor transcription studies in chloramphenicol acetyl transferase assays
      showed that EB 1213 and GS 1500 were more efficient than 1 alpha,25(OH)2D3 in
      inducing vitamin D receptor transcription. This strongly indicates that not only
      the binding affinity for the receptor, but more importantly, the ability of the
      compounds to induce vitamin D receptor transcription, is a determinant of the
      biological activity of the compounds.

PMID- 9627692
TI  - Vitamin D analogs affect the uptake and metabolism of retinol by human epidermal
      keratinocytes in culture.
AB  - Human epidermis utilizes retinol as precursor for local production of a range of
      bioactive vitamin A metabolites including 3,4-didehydroretinol, retinoic acid,
      and 3,4-didehydroretinoic acid. These endogenously formed retinoids bind to
      nuclear retinoic acid receptors (RARs), thereby altering gene transcription.
      Because 9-cis-retinoic acid receptors (RXRs) form heterodimers both with RARs and
      the vitamin D3 receptor (VDR), it is plausible that vitamin D3 may affect retinol
      metabolism if altered transcription is involved in the regulation of vitamin A
      metabolizing enzymes. To investigate the potential effect of vitamin D on retinol
      metabolism in human skin keratinocytes, HaCaT cells were preincubated with
      various vitamin D3-analogs at 10(-7)M for 24 h followed by the addition of
      [3H]retinol for another 24 h period. The uptake and metabolism of the radioactive
      tracer was monitored by HPLC-radiochromatography. It was found that all synthetic
      vitamin D-analogs tested (MC903, KH1060, EB1089, and EB1213) reduced the amount
      of cell-associated [3H]retinoid activity by 35-50% as compared to the vehicle.
      More specifically, the appearance of the parent substrate and two of its main
      metabolites, e.g., 3,4-didehydroretinol (ddROH) and 3,4-didehydroretinoic acid
      (ddRA), was inhibited by the synthetic vitamin D-analogs. The effects on retinol
      metabolism were not potentiated by coincubation of cells with vitamin D-analogs
      plus retinoic acid (RA) or 9-cis-RA. This study demonstrates that synthetic
      vitamin D3 interferes with both the uptake and the metabolism of retinol by human
      epidermal keratinocytes. Whether the effects are due to direct inhibition of
      cellular retinol uptake and metabolism or involve VDR-mediated transcriptional
      alteration of vitamin A metabolizing enzymes remains to be clarified.

PMID- 9627693
TI  - Calcitriol and its analog KH 1060 induce similar changes in keratinocyte cell
      cycle progression after topical application to mouse skin. A bromodeoxyuridine
      pulse-chase flow cytometric study.
AB  - Calcitriol and its analogs are used in the treatment of psoriasis and may also
      induce epidermal proliferation, hyperplasia, and irritation in normal skin by an
      unknown mechanism. The effects of a single dose of calcitriol and the 20-epi
      vitamin D3 analog KH 1060 were therefore examined by performing 5-bromo-2'
      deoxyuridine (BrdU) pulse chase labeling experiments in unperturbed hairless
      mouse epidermis in vivo. One cohort of basal cells was exposed to calcitriol
      mainly during the S phase, whereas another cohort in G1/G0 phase was stimulated
      by calcitriol or KH 1060 into S phase 16 h before BrdU labeling. Basal
      keratinocytes were isolated from epidermis and analyzed by bivariate BrdU/DNA
      flow cytometry. Calcitriol and KH 1060 induced similar proliferative responses,
      with a peak of cells in S phase at about 16 h after drug applications. The
      cohorts in G1/G0 phase at the time of drug application displayed a reduced cell
      cycle, whereas the cohort of cells in S phase at the time of calcitriol
      application did not show a similar reduction. The proliferation kinetics observed
      are thus different from those seen after retinoic acid treatment, since retinoic
      acid did not reduce the cell cycle time under similar conditions. Reduction of
      cell cycle time may be a characteristic effect of calcitriol and KH 1060, similar
      to that seen after other hyperplasiogens. The results also indicate that the
      drugs exert differential effects on cells depending on the cells' position in the
      cell cycle during treatment.

PMID- 9627694
TI  - Toxicity of 1,25-dihydroxyvitamin D3, tacalcitol, and calcipotriol after topical
      treatment in rats.
AB  - To investigate and compare the effects on calcium metabolism of 1,25
      dihydroxyvitamin D3 (1,25(OH)2D3) and the synthetic vitamin D analogs tacalcitol
      and calcipotriol after topical treatment, we treated groups of rats topically
      once daily with three dose levels of each test compound in a vehicle of propylene
      glycol plus ethanol for 28 d. The urinary calcium excretion was measured after 14
      d, and serum calcium and parathyroid hormone were measured at termination. The
      rats were autopsied, and the kidneys were examined microscopically for
      mineralizations. Based on the urinary calcium excretion and the serum calcium
      level, calcipotriol was found to be 60 times less calcemic, and tacalcitol was
      slightly less calcemic, than 1,25(OH)2D3 after repeated topical application to
      rats. Serum parathyroid hormone was suppressed to a lower degree by calcipotriol
      and tacalcitol than by 1,25(OH)2D3, and the incidence and severity of renal
      corticomedullary mineralization were higher in rats treated with 1,25(OH)2D3 and
      tacalcitol than with calcipotriol. We conclude that calcipotriol is much less
      calcemic than 1,25(OH)2D3 or tacalcitol when applied topically to rats in a
      vehicle that enhances penetration into the skin. We attribute the lower calcemic
      effect of calcipotriol to the pharmacokinetic profile of the compound,
      particularly its rapid metabolization into inactive compounds.

PMID- 9627695
TI  - Toxicokinetics of topically applied calcitriol and calcipotriol in rats.
AB  - Two topically applied vitamin D analogs were investigated for their effects on
      calcium homeostasis in the rat. Calcitriol ointment (3 micrograms/g),
      calcipotriol ointment (50 micrograms/g), or vehicle were applied daily for 4 days
      on the shaven back of the rats (n = 5 per group) over an area of 75 cm2. Blood
      and urine samples were collected before and during treatment and for 7 days after
      the last dose. Application of calcipotriol ointment resulted in a significant
      increase in urinary calcium and phosphate excretion and severe down-regulation of
      endogenous calcitriol levels, up to 7 days after the last dose. Calcipotriol
      could still be detected in the last plasma sample. In contrast, calcitriol
      ointment had no significant effects relative to vehicle on any of the parameters
      studied. Calcitriol ointment (3 micrograms/g) does not appear to affect calcium
      homeostasis in rats, whereas calcipotriol ointment has a prolonged effect.

PMID- 9627696
TI  - 1,25-Dihydroxyvitamin D3 as a natural regulator of human immune functions.
AB  - 1,25-dihydroxyvitamin D3 (1,25-D3) modulates lymphocyte and macrophage functions
      in vitro. These effects are exerted through production of 1,25-D3 by antigen
      presenting monocytes/macrophages (MO) and binding to vitamin D receptors
      expressed in MO and in activated, but not in resting T-lymphocytes. 1,25-D3
      inhibits production of MO-derived cytokines such as interleukin-1 alpha,
      interleukin-6, and tumor necrosis factor alpha at the post-transcriptional level,
      most likely by reducing the half-life of specific mRNAs. The proliferation of T
      cells and their release of cytokines such as IL-2 and interferon gamma are also
      suppressed by 1,25-D3, partly as a result of the reduced production of T-cell
      activating cytokines (interleukin-1 alpha, tumor necrosis factor alpha), but also
      because of a direct effect on the T-cells. Although 1,25-D3 has no apparent
      effect on B-lymphocytes, the T-cell suppression indirectly inhibits antibody
      production by B-cells. The CD45R0+ subset of T-helper cells is relatively more
      sensitive than the CD45RA+ subset to the inhibitory effects of 1,25-D3. The
      CD45R0+ subset plays a key role in immune activation and in the pathogenesis of
      many autoimmune disease. 1,25-D3 acts as an important local regulator of T-cell
      functions and thus modulates several immunological effector functions. The
      actions of 1,25-D3 are distinct from those of commonly used immunosuppressants,
      and vitamin D3 analogs are therefore potentially useful as alternatives to
      conventional immunosuppressive therapies.

PMID- 9627697
TI  - The vitamin D3 analog calcipotriol suppresses the number and antigen-presenting
      function of Langerhans cells in normal human skin.
AB  - Local activation of T lymphocytes appears to play an important role in psoriasis
      and autoimmune skin disease. 1 alpha,25-dihydroxyvitamin D3 and the vitamin D3
      analog calcipotriol have been shown to inhibit immune induction in vitro. The
      purpose of the present study was to investigate the in vivo effect of
      calcipotriol on Langerhans cells in normal human skin and to determine the effect
      of 1,25-dihydroxyvitamin D3 and calcipotriol on isolated Langerhans cells to
      induce autologous T-cell proliferation. Using confocal laser scanning microscopy
      of epidermal suction blister roofs, it was found that application of calcipotriol
      cream to normal human skin for 4 d resulted in a dose-dependent decrease in the
      number of CD1a+ cells with a dendritic morphology and in the number of dendrites
      per cell. The suppressive effect of calcipotriol on Langerhans cells was as
      strong as that of the potent corticosteroid mometasonfuroate. In Langerhans cell
      enriched cell suspensions (60-97% pure) isolated from normal human skin, 1,25
      dihydroxyvitamin D3 and calcipotriol (10(-8)-10(-7) M) significantly suppressed
      their ability to stimulate antigen-dependent T-cell proliferation. Furthermore,
      the vitamin D receptor was detected by Western blot analysis in the isolated
      Langerhans cells. Neither immunohistochemical studies nor flow cytometry of
      Langerhans cells showed any change in the human leukocyte antigen-DR expression
      after 48 h culture with antigen with or without calcipotriol. It is proposed that
      the inhibitory effects of the vitamin D3 on Langerhans cells may induce
      immunosuppression in the skin.

PMID- 9627698
TI  - Reduction of epidermal abnormalities and inflammatory changes in psoriatic
      plaques during treatment with vitamin D3 analogs.
AB  - Vitamin D3 analogs interfere with various aspects of epidermal growth,
      inflammation, and cellular differentiation. Most data are derived from in vitro
      studies. In the present review, the in vivo effects of vitamin D3 analogues on
      the psoriatic plaque are discussed. Calcipotriol, tacalcitol, and calcitriol in
      ointment modulate aspects of epidermal growth, differentiation, and inflammation.
      Immunohistochemical studies suggest that the inflammatory changes might be more
      expressed after treatment with calcitriol and tacalcitol. Flow cytometric
      quantification of the percentage of cells in SG2M phase and of keratin 10
      positive cells revealed that calcipotriol reduced both indices significantly
      during treatment of psoriatic plaques. Flow cytometric analysis of epidermal cell
      suspensions using triple labeling for epidermal proliferation, expression of
      keratin 10, and vimentin permits a quantitative assessment of DNA synthesis
      selectively in the basal cells of the epidermis, an estimation of the
      distribution of the basal and suprabasal compartments, and a quantification of
      the distribution of mesenchymal and nonmesenchymal cells. Using this approach,
      the interference of tacalcitol with growth control of basal cells was
      demonstrated. Remarkably, recompartmentalization of basal and suprabasal cells
      and mesenchymal and nonmesenchymal cells proved to be inconspicuous during this
      treatment.

PMID- 9627699
TI  - Vitamin D-retinoid association: molecular basis and clinical applications.
AB  - The molecular structure of the biological active form of vitamin D, 1 alpha,25
      dihydroxyvitamin D3 (VD), and the vitamin A derivatives all-trans and 9-cis
      retinoic acid (RA) are not related. The nuclear receptors for VD (VDR) and
      retinoids (RAR and RXR), however, are members of the same superfamily of ligand
      activated transcription factors. We observed stable VDR-RXR and VDR-RAR
      heterodimers in solution and their transcriptional activity on different types of
      response elements. Both heterodimeric complexes are activated by VD, but,
      depending on the relative expression of the nuclear receptors, retinoids can have
      either co-stimulating or repressing effects. This demonstrates that VD and
      retinoid signaling are linked at the level of gene regulation and may explain the
      similar effects of both hormones on cell proliferation and differentiation. This
      concept may be applied for treating skin diseases, with the hope that a synergism
      will be observed, allowing better responses with lower doses of each compound.
      Preliminary observations suggest that psoriasis, cutaneous T-cell lymphomas, and
      actinic keratoses might be potential targets for VD-retinoid associations.

PMID- 9627700
TI  - 1,25-Dihydroxyvitamin D3 and its synthetic derivatives MC903 and EB1089 induce a
      partial tumoral phenotype reversal in a skin-equivalent system.
AB  - The antitumoral potency of 1,25-dihydroxyvitamin D3 and its synthetic derivatives
      MC903, EB1089, and KH1060 was investigated on a tumoral Bowen-like epidermis
      reconstructed from an immortalized human keratinocyte cell line transfected by
      expression vectors coding for E6 and E7 of human papillomavirus 16. Treatment of
      skin equivalents by vitamin D derivatives (10(-9) M or 10(-12) M) was performed
      during (from day 1 to day 15 of culture) or after tissue reconstruction (from day
      15 to day 30). Pharmacologic effects were evaluated by morphologic and
      immunohistologic analysis and compared with those of controls (vehicle alone) and
      with treatment of skin equivalents derived from normal keratinocytes. When
      performed during epidermal reconstruction, treatment of tumoral skin equivalents
      induced only minor morphologic and immunohistologic changes. Conversely, when
      performed after epidermal reconstruction, treatment with 1,25-dihydroxyvitamin
      D3, MC903, and EB1089 clearly improved the phenotype of treated tissues.
      Morphologic analysis showed reorganization of epidermal layers with the
      appearance of a distinct basal layer and of stratified orthokeratotic stratum
      corneum. Immunohistochemical analysis demonstrated that the terminal
      differentiation markers profilaggrin and cytokeratin 10 were re-expressed in the
      treated tissues while absent in controls. Overall, the results indicate that 1,25
      dihydroxyvitamin D3, MC903, and EB1089 can induce a partial reversion of the
      tumoral phenotype in this in vitro model.

PMID- 9627701
TI  - Anti-tumor effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in seborrheic
      keratosis.
AB  - 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is a drug with potent antiproliferative
      action on keratinocytes that have nuclear receptors for 1,25(OH)2D3. We
      investigated the effects of 1,25(OH)2D3 on widespread seborrheic keratoses in 51
      patients with these tumors. The data indicated that resolution of these tumors
      was dependent on both tumor size and dose of 1,25(OH)2D3. Among 15 patients
      treated with a high dose (0.5 microgram/d) of oral 1,25(OH)2D3, the lesions of
      widespread seborrheic keratoses changed from brown-black papules to brownish
      papules with erythema and/or crust as early as 2 wk after the start of treatment.
      The tumors finally developed into an atrophic scar or brownish pigmented macule.
      Histologically, vacuolation of the spinous cells, vesicle formation, and
      liquefaction degeneration of the basaloid cells were observed. Numerous
      lymphocytes had infiltrated in the papillary dermis. Among 36 patients treated
      with a low dose (0.25 microgram/d) of 1,25(OH)2D3, brownish papules became pale
      to normal in color and reduced in size, without erythematous change.
      Histologically, acanthosis of the epidermis was reduced, but degenerative change
      of the tumor cells was not observed. These data suggest that oral therapy of
      1,25(OH)2D3 is an acceptable method well suited to the removal of seborrheic
      keratoses, especially those that are predominantly small tumors.

PMID- 9627702
TI  - Vitamin D3 is a potent inhibitor of tumor cell-induced angiogenesis.
AB  - Vitamin D3 derivative 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) exerts various
      biological effects in cells that possess vitamin D3 receptor (VDR), including
      enhancement of cell differentiation and inhibition of cell proliferation. These
      activities of 1,25(OH)2D3 might be responsible for its anti-neoplastic effects,
      as shown in various experimental systems. The aim of this study was to compare
      the anti-angiogenic activity of 1,25(OH)2D3, retinoids, and interleukin-12 (IL
      12) in an experimental tumor cell-induced angiogenesis assay in mice. Tumor cell
      induced angiogenesis assay was performed in x-ray immunosuppressed BALB/c mice by
      intradermal injections of human tumor cell lines of different origin. The
      injections resulted within 3 d in a local formation of new blood vessels, and the
      intensity of angiogenesis correlated with the number of injected cells. Systemic
      treatment of the mouse recipients with 1,25(OH)2D3 significantly decreased
      angiogenesis, comparable to the effect of retinoids (all-trans retinoic acid
      [RA], 9-cis RA and 13-cis RA) and of IL-12. In vitro preincubation of the cells
      with all compounds (except IL-12) led to the inhibition of their angiogenic
      capability in vivo. Moreover, combination of 1,25(OH)2D3 and retinoids resulted
      in a synergistic inhibition of angiogenesis. The results strongly suggest that
      anti-angiogenic compounds with relatively low toxicity (e.g., 1,25(OH)2D3,
      retinoids, and IL-12) and their combinations could be beneficial in the treatment
      of some angiogenesis-associated malignancies.

PMID- 9627703
TI  - p53: at the crossroads of molecular carcinogenesis and molecular epidemiology.
AB  - The p53 tumor suppressor gene is frequently mutated in human cancer, including
      squamous cell carcinoma and basal cell carcinoma of the skin, but is rarely
      mutated in skin melanoma. The p53 mutation spectrum provides insight into both
      the etiology of human cancer and the functional regions of the encoded protein
      that lead to clonal expansion of the p53 mutant cell.

PMID- 9627704
TI  - Signal transduction and the regulation of cell growth.
AB  - The need to understand and characterize critical steps controlling mitogenesis is
      a problem being addressed in many laboratories today. Genetic damage in cancer
      cells is a universal characteristic, and the search for the targets of this
      damage has led to the study of numerous complex signal transduction pathways
      which are involved in regulating cellular proliferation and differentiation. One
      important signal transduction cascade involved in controlling mitogenesis is the
      mitogen-activated protein kinase pathway. It is now clear that both tyrosine
      kinase growth factor receptors and G protein-coupled receptors regulate this
      pathway. Recent work from many groups has resulted in the initial
      characterization of the events that lead to mitogen-activated protein kinase
      activation by these different receptors. This review will contain a brief
      background of G proteins and their potential role in controlling cell growth.

PMID- 9627705
TI  - Cell cycle control and cancer: lessons from lung cancer.
AB  - Recent developments in the study of the cell cycle have shed much light on the
      origins of human cancer. We summarize these developments with an emphasis on the
      molecular characterization and the functional role of the cyclin-dependent kinase
      family of protein kinases (CDK) and their associated regulatory subunits. The Rb
      tumor suppressor in the progression from the G1 to S phase of the cell cycle and
      in tumor development is used as a paradigm for illustrating the importance of
      understanding the molecular regulatory events in the etiology of cancer. Recent
      developments with cyclin-dependent kinase inhibitors, most notably, p16 (CDKN2),
      indicate that these molecules represent new tumor suppressors in both skin and
      lung cancers. Insights from these cell cycle studies can provide avenues for the
      diagnosis, prognosis, and potential gene and chemotherapies for many cancers,
      including non-small cell lung cancer.

PMID- 9627706
TI  - Functional interactions among members of the Myc superfamily and potential
      relevance to cutaneous growth and development.
AB  - Myc family oncoproteins function as sequence-specific transcription factors that
      are believed to regulate the expression of genes governing cellular growth,
      differentiation, and programmed cell death. Activities of Myc are countered by
      those of Mad and Mxi1, two related members of the Myc superfamily. Mad and Mxi1
      compete with Myc for common elements and interact with putative transcriptional
      repressors. While the precise role of the Myc superfamily in cutaneous biology
      remains to be determined, findings from a number of organ systems suggest that
      the regulated expression and function of its members are intimately correlated
      with proper development and physiology. Reviewed here are current data on Myc
      superfamily function with references where relevant to cutaneous processes with
      the ultimate goal of providing a framework upon which these proteins can be
      exploited in gene therapeutic approaches for diseases of the skin, including
      neoplasia.

PMID- 9627707
TI  - Sunlight and sunburn in human skin cancer: p53, apoptosis, and tumor promotion.
AB  - Sunlight is a carcinogen to which everyone is exposed. Epidemiology indicates
      that most carcinogenic sunlight exposure takes place several decades before the
      tumor arises. Some of the early events have been identified by searching for
      genes having ultraviolet (UV)-specific mutations. Over 90% of squamous cell
      carcinomas and more than 50% of basal cell carcinomas from New England patients
      contain UV-like mutations in the p53 tumor suppressor gene. From the mutation
      pattern, it can be concluded that the carcinogenic DNA lesions were pyrimidine
      cytosine photoproducts caused by the UVB portion of sunlight. Particular codons
      of the p53 gene are most susceptible, apparently because of slower DNA repair at
      specific sites. Sunlight is sufficiently mutagenic often to mutate both p53
      alleles. These mutations are also found in the precancer for squamous cell
      carcinoma, actinic keratosis, implying an early role. The function of p53 in
      normal skin is indicated by the observation that inactivating p53 in mouse skin
      reduces the appearance of sunburn cells, apoptotic keratinocytes generated by UV
      overexposure. Skin thus appears to possess a p53-dependent "cellular
      proofreading" response to DNA damage in which precancerous cells self-destruct.
      If this response is reduced in a single cell by a prior p53 mutation, sunburn can
      thereafter select for clonal expansion of the p53-mutated cell into an actinic
      keratosis. Sunlight appears to act twice: as tumor initiator and as tumor
      promoter.

PMID- 9627708
TI  - The immune system in ultraviolet carcinogenesis.
AB  - The immune system plays an important role in ultraviolet (UV) carcinogenesis by
      contributing to host resistance against skin cancer development. UV radiation,
      however, circumvents immune surveillance against skin cancers by modulating the
      immune response in a way that favors tumor development. Studies addressing the
      cellular mechanisms by which UV radiation modifies immune function are
      summarized. These studies demonstrate that UV irradiation of the skin produces
      both local, nonspecific immune suppression that inhibits immune effector
      functions within irradiated skin, as well as systemic, specific immune
      suppression against antigens introduced at a critical time after exposure to UV
      radiation. Evidence is presented suggesting that the production of cytokines by
      epidermal cells in response to UV-induced DNA damage is an important component of
      UV-induced specific immune suppression.

PMID- 9627709
TI  - Multistage carcinogenesis in the skin.
AB  - The multistage evolution of squamous cell cancer on mouse skin has provided a
      model to dissect the biological and genetic changes that contribute to specific
      stages of carcinogenesis. Keratinocyte cell culture models have been developed
      that reproduce the genetic and epigenetic events in multistage skin
      carcinogenesis, and these provide insights into the biochemistry of the process.
      When the v-rasHa oncogene is transduced into normal mouse keratinocytes, the
      resultant papilloma phenotype is characterized by a high rate of cell
      proliferation, an aberrant program of differentiation marker expression, and
      resistance to terminal differentiation. These changes are attributed to
      differential effects on isoforms of protein kinase C coupled to activation of the
      epidermal growth factor receptor. Premalignant progression requires additional
      genetic changes in the v-rasHa-transduced cells. The acquisition of these changes
      is suppressed by transforming growth factor beta (TGF beta), and the absence of
      TGF beta in premalignant tumors indicates a high risk for malignant progression.
      Keratinocytes that are genetically null for the TGF beta 1 gene rapidly progress
      to squamous cell carcinomas when transduced with the v-rasHa oncogene. In
      culture, TGF beta 1 null keratinocytes exhibit a high rate of gene amplification
      that can be suppressed by concentrations of exogenous TGF beta well below those
      required to inhibit proliferation. This model is well-suited to identifying
      critical genetic changes that contribute to premalignant progression.

PMID- 9627710
TI  - The mouse skin carcinogenesis model.
AB  - Skin carcinogenesis can be divided into at least three major stages: initiation,
      promotion, and progression. In the mouse skin model, the first stage is thought
      to involve the interaction of a tumor initiator with the genetic material of stem
      cells, leading to an irreversible alteration in growth control or
      differentiation, probably by activation of the Ha-ras oncogene. The major effect
      of all skin-tumor promoters seems to be the specific expansion of the initiated
      stem cells. The correlation between the abilities of tumor promoters to induce
      sustained hyperplasia and their tumor-promoting activities is very good. We found
      that the appearance of alpha-glutamyl transpeptidase (GGT) and keratin 13 and the
      lack of expression of keratins 1 and 10 are good markers for skin tumor
      progression. These alterations occur when papillomas change from a diploid to an
      aneuploid state, mainly as a result of developing trisomies 6 and 7. To evaluate
      the role of GGT in skin-tumor progression, we transfected a functional GGT cDNA
      into two cell lines that normally produce papillomas when grafted into the skin
      of nude mice. When injected subcutaneously, all of the GGT-transfected clones
      formed malignant tumors, whereas only 24% of vector-transfected cells did. When
      GGT-transfected clones were placed into grafts, the grafts had an average mass
      almost three times that of grafts of vector-transfected cells. Our recent studies
      also suggest that the ribonucleoprotein telomerase and the gap-junctional
      proteins connexins (Cxs) are also important in skin-tumor progression. A
      progressive increase in telomerase activity was associated with the increased
      level of genomic instability during tumor progression. In addition, the level and
      expression of Cx26, Cx43, and Cx31.1 were significantly altered during skin tumor
      promotion and progression. The differences of various mouse stocks and strains in
      susceptibility to multistage skin carcinogenesis seem to be related more to
      alterations in tumor promotion than to tumor initiation; however, the critical
      events have not been determined. Results with an inbred strain of SENCAR mice,
      which are very sensitive to papilloma formation by the two-stage protocol, also
      suggest that susceptibility is related to promotion. Despite the high incidence
      of papillomas in these inbred SENCAR mice, the number of malignant tumors was
      extremely low, suggesting that sensitivity to promotion and progression are
      independent in these mice.

PMID- 9627711
TI  - Differential regulation of integrins and extracellular matrix binding in
      epidermal differentiation and squamous tumor progression.
AB  - Cell surface receptors of the integrin family regulate physiological and
      pathological processes in skin, including proliferation, differentiation, and
      malignant transformation. In skin, integrins are compartmentalized. While alpha 6
      beta 4 is restricted to the basal surface of basal cells, beta 1 integrins are
      expressed in basal and suprabasal layers. In vivo and in Ca(2+)-induced
      differentiation of mouse keratinocytes in vitro, the loss of attachment to
      laminin via alpha 6 beta 4 integrin is an early event associated with initiation
      of spinous differentiation. The restricted expression of alpha 6 beta 4 to the
      basal cells in normal skin is disrupted early in the development of squamous
      cancer, where benign papillomas at high risk for malignant progression express
      alpha 6 beta 4 suprabasally in an expanded proliferative compartment. The
      aberrant suprabasal alpha 6 beta 4 is associated with reduced keratin 1
      expression and upregulation of keratin 13, keratin 8, and gamma
      glutamyltranspeptidase. During malignant conversion, the increase in alpha 6 beta
      4 protein and mRNA is associated with novel expression of an alternatively
      spliced form of the alpha 6 subunit, alpha 6B. The induction of alpha 6B both in
      vivo and in vitro is particularly high in malignant cells produced by
      transduction of both v-fos and v-rasHa oncogenes into normal keratinocytes where
      it was associated with increased attachment to laminin. Furthermore, binding to
      laminin is increased by introduction of alpha 6B into a papilloma cell line.
      These results establish a link between squamous tumor progression and the
      upregulation of the alpha 6 beta 4 integrin and suggest that expression of alpha
      6B could be functionally relevant to interaction of tumor cells with the laminin
      matrix during malignant conversion.

PMID- 9627712
TI  - Multistage epidermal carcinogenesis in transgenic mice: cooperativity and
      paradox.
AB  - Skin cancer is one of the most prevalent forms of human neoplasia with a
      frequency approaching that of all other neoplasms combined. Given this alarming
      statistic, which may be further exacerbated by increased ultraviolet B
      irradiation from ozone depletion, it is vital that realistic, relevant model
      systems are developed to increase our understanding of the underlying molecular
      mechanisms of carcinogenesis that result in or evaluate new treatment modalities.
      Toward this goal, the ability to stably introduce genes into the germline of mice
      has greatly enhanced prospects for generation of transgenic animal models of
      multistage molecular carcinogenesis. Moreover, when genes are combined with
      regulatory sequences that target their expression to specific tissues,
      investigators are able to study neoplasia both in the context of living organisms
      and in the tissues suspected of being the targets of these genes. The epidermis
      is an attractive tissue for targeted gene expression; not only is it a model for
      epithelial diseases in general, but the accessibility of the epidermis allows
      easy detection of progressive pathological changes that result from transgene
      expression and facilitates assessment of the potential role played by
      environmental factors. We have developed a targeting vector based on the human
      keratin gene (HK1), which is expressed exclusively in the epidermis of transgenic
      mice, at a late stage in development and in both basal and differentiated cells.
      Through the use of this targeting ability, rasHa, fos, and TGF alpha transgenic
      mice have been developed that exhibit preneoplastic epidermal hyperplasia and
      hyperkeratosis, and later benign, regression prone papillomas. Together,
      coexpression of two oncogenes cooperated to give autonomous papillomas, which
      possessed the phenotypic stability to allow assessment of a third genetic event,
      namely loss of the p53 tumor suppressor gene, via mating with p53 knockout mice.
      Loss of p53 expression, however, identified a paradoxical block of
      papillomatogenesis. This latter result suggests that the epidermis possesses
      several mechanisms that can effectively compensate for the loss of important
      tumor suppressor functions and may have evolved to render the skin relatively
      resistant to the effects of environmental carcinogens.

PMID- 9627713
TI  - Human melanoma genetics.
AB  - Melanoma is an important human cancer, the etiology of which has been the subject
      of much study. Recently a gene for familial melanoma, MLM, has been mapped and
      isolated. This gene encodes the cell-cycle regulator p16 and is mutated in a
      variety of sporadic human cancers in addition to melanoma. The isolation of MLM
      answers some questions in the area of melanoma biology, but raises others.
      Identification of p16 and other genes that contribute to melanoma development may
      be viewed as one step in the attempt to understand, diagnose, and treat this
      malignant disease.

PMID- 9627714
TI  - Analysis and significance of the malignant 'eclipse' during the progression of
      primary cutaneous human melanomas.
AB  - Why is it that primary melanomas which are less than 0.76 mm in thickness are
      almost always curable by surgery whereas thicker lesions are associated with a
      worse prognosis? Put in another way, why is it that such small increases in tumor
      thickness beyond 0.76 mm are often associated with the eventual formation of
      distant metastases and death? Part of the answer lies in the dramatic qualitative
      changes which can accompany small increases in the size of primary human
      melanomas. Thus, primary melanomas less than 0.76 mm in thickness usually contain
      very low proportions of metastatically competent tumor cells, whereas slightly
      thicker lesions can contain very high proportions of such cells, resulting from a
      selective growth advantage of the latter in the dermal mesenchyme. This
      overgrowth process is akin to a 'malignant eclipse' phenomenon (by analogy with a
      solar eclipse). We have been studying the causes of the malignant eclipse in
      melanoma, for which there are at least four possibilities: 1) an increase in
      autocrine, mitogenic growth factors by melanoma cells; 2) a decreased rate of
      apoptosis in the same population; 3) an acquired resistance to paracrine growth
      inhibitory factors; and 4) an increased ability to induce an angiogenic response.
      Evidence exists for all four possibilities. Our experimental approach to studying
      this problem has relied heavily on the use of cell lines obtained from early
      stage radial growth phase or vertical growth phase lesions which have a clinical
      like inability to grow progressively in nude mice, and variants obtained from
      such lines which are aggressively tumorigenic. Using such paired lines, and other
      experimental systems, we have obtained evidence that shows early stage melanoma
      cell lines may be deficient in inducing angiogenesis, are highly sensitive to the
      growth inhibitory effects of a plethora of cytokines, including transforming
      growth factor beta, interleukin-6, and oncostatin M, and are more sensitive to
      undergoing spontaneous apoptosis in several conditions including when growth in
      anchor-age-independent, 3-dimensional tissue culture. How this information may
      impact tumor prognosis and the design and effects of new strategies to treat
      melanoma, especially antiangiogenesis strategies, is discussed.

PMID- 9627715
TI  - Shifts in cadherin profiles between human normal melanocytes and melanomas.
AB  - Direct contacts between keratinocytes and melanocytes play an important role in
      conserving the characteristic phenotype and biologic behavior of melanocytic
      cells. Although the mechanisms involved remain unclear, given the role of
      adhesion molecules in controlling cellular interactions, disturbances in normal
      keratinocyte-melanocyte adhesion mediated by cadherin may contribute to malignant
      transformation by releasing melanocytes from a variety of contact-mediated
      regulatory controls. To determine the potential clinical relevance of cadherin
      profiles in melanomas and to study their possible involvement in the phenotypic
      plasticity of melanocytic cells, we used immunostaining, biochemical, and co
      culture techniques. Double immunofluorescence demonstrated expression of
      cadherins and their associating proteins, alpha- and beta-catenin, in melanocytes
      in situ. Melanomas were heterogeneous when evaluated immunohistochemically, with
      positive rates of four of 14, eight of 12, and 12 of 16 to anti-E-, anti-P-, and
      anti-N-cadherin monoclonal antibodies, respectively. Flow cytometry indicated
      abundant expression of E-cadherin but marginal P- and N-cadherin in cultured
      melanocytes. In contrast, only one (WM1232) of 16 melanoma cell lines tested was
      positive for E-cadherin, none was positive for P-cadherin, and all but one were
      positive for N-cadherin. Western blot confirmed E-cadherin expression in
      melanocytic cells. Immunoprecipitation further revealed complexes of E-cadherin
      with catenins in WM1232 melanoma cells. Co-culture studies indicated that only
      melanoma cells expressing E-cadherin (WM1232) were susceptible to keratinocyte
      mediated control of the expression of the melanoma cell adhesion molecule, Mel
      CAM. The results suggest downregulation of E-cadherin but upregulation of N
      cadherin in melanoma cells. Such a shift in cadherin profiles may endow
      melanocytic cells with new adhesive properties and altered spatial relations that
      favor uncontrolled proliferation, migration, and invasion.

PMID- 9627716
TI  - Induction of melanogenesis during the various melanoma growth phases and the role
      of tyrosinase, lysosome-associated membrane proteins, and p90 calnexin in the
      melanogenesis cascade.
AB  - Melanin biosynthesis (melanogenesis) is a metabolic pathway exclusively expressed
      by melanocytes and melanoma cells, and is often altered and/or markedly elevated
      in the latter cells. The changes in melanogenesis may be responsible for some of
      the clinical and histopathological features unique to melanoma. Melanogenesis may
      also contribute to the malignant transformation of melanoma precursors (i.e.,
      atypical moles [or dysplastic nevi]) to melanoma as seen in patients with the
      familial atypical multiple-mole-melanoma (FAMMM) syndrome. However, it does not
      appear to affect the multi-step growth phases of melanoma cells from radial to
      vertical and lastly metastatic growth phases. Within the melanosomal compartment,
      eu- and pheomelanin pigments are synthesized. Both tyrosinase and lysosome
      associated membrane protein (LAMP) gene products play important roles in this
      process. A coordinated interaction between these two gene family products is
      required for melanogenesis to occur properly. p90 calnexin is a new melanosome
      associated molecule that is presumed to function as a melanogenesis chaperone by
      controlling the assembly and folding of glycoprotein intermediates of tyrosinase
      and LAMP gene families.

PMID- 9627717
TI  - Critical determinants of melanoma metastasis.
AB  - The process of metastasis consists of a series of linked, sequential steps.
      Although some of the steps in this process contain stochastic elements,
      metastasis as a whole favors the survival and growth of a few subpopulations of
      cells that preexist within the parent neoplasm. Metastases can have a clonal
      origin, and different metastases can originate from the proliferation of single
      cells. The outcome of metastasis depends on the interaction of metastatic cells
      with various host factors. Organ-specific metastases have been demonstrated in a
      variety of tumors and may even be specific to a particular site within one organ.
      Studies from our laboratory and from others have shown that the implantation of
      human cancer cells derived from surgical specimens into correct anatomic sites of
      nude mice provides a suitable model of metastasis of human tumors. Clonal
      analysis of human melanomas revealed that these tumors are heterogeneous for
      metastatic properties and that growth in the environment of specific organs is
      selective. These data suggest that systemic physiologic signals can be recognized
      by neoplastic cells, presumably by mechanisms similar to those shared by their
      normal cell counterparts. Elucidation of the mechanisms that regulate metastasis
      should lead to better therapeutic interventions.

PMID- 9627718
TI  - Skin cancer chemoprevention.
AB  - Chemoprevention of cancer is a means of cancer control in which the occurrence of
      this disease, as a consequence of exposure to carcinogenic agents, can be
      entirely prevented, slowed, or reversed by the administration of one or several
      naturally occurring or synthetic agents. Thus, the chemoprevention of cancer
      differs from therapy in that the goal of prevention is to lower the rate of
      cancer incidence. Such chemopreventive agents are also known as anticarcinogens,
      and an ideal agent should have (i) little or no untoward or toxic effects, (ii)
      high efficacy against multiple sites, (iii) capability of oral administration,
      (iv) a known mechanism of action, (v) low cost, and (vi) human acceptance. With
      regard to naturally occurring agents, fruits, vegetables, and common beverages,
      as well as several herbs and plants, have been identified as rich sources of
      cancer chemopreventive agents. While a wide range of laboratory studies has
      identified many compounds, including several polyphenols, as cancer
      chemopreventive agents, in this article our main emphasis is on the cancer
      chemopreventive potential of a polyphenolic fraction isolated from green tea and
      silymarin, a flavonoid present in artichoke, against different stages of mouse
      skin multistage carcinogenesis. We also highlight studies related to retinoid
      effects on prevention of human skin cancers.

PMID- 9627719
TI  - Immunotherapy of melanoma.
AB  - Melanoma is one of the first tumors for which several types of immunotherapy have
      been applied extensively. It is becoming clear that although only a minority of
      patients respond to immunotherapy, those who do have a major clinical response
      experience an improvement in survival. Melanoma vaccines (active specific
      immunotherapy) have elicited clinical remissions in advanced disease, in some
      instances for years. They may have extended survival in resected stage II or III
      disease, although the results of controlled, randomized trials in these stages
      are still pending. Perhaps their major advantage is their nearly total lack of
      significant systemic toxicity. Gene-modified whole-cell vaccines, newer
      constructs involving cell membranes on synthetic beads, and purified immunogenic
      peptides are interesting second-generation vaccines. Cytokines such as interferon
      alpha and interleukin-2 also have had a beneficial effect in approximately 20% of
      patients with advanced disease, with a suggestion of higher rates of response
      when interferon is combined with a vaccine. A randomized, controlled Intergroup
      study has shown that interferon-alpha at 10 million U/m2/d three times weekly for
      2 y is superior to observation alone in prolonging relapse-free and overall
      survival in resected stage III patients. Other such trials are necessary to prove
      the usefulness of immunotherapy in melanoma, but its promise as a new approach to
      a difficult disease is already evident.

PMID- 9627720
TI  - Retinoids and interferons in non-melanoma skin cancer.
AB  - Retinoids alone and in combination with interferon-alpha are the best systemic
      agents to study in the reversal of skin carcinogenesis and in the treatment of
      advanced squamous cell carcinoma of the skin. This article reviews the major
      laboratory advances in the mechanistic study of retinoids and interferons alone
      and in combination. Recent data in several cancer cell lines suggest that
      retinoic acid can potentiate the interferon signal-transduction pathway. Also
      reviewed is the current status of clinical studies of systemic retinoids and
      interferon in (i) skin cancer prevention (as single agents) and (ii) treatment of
      advanced squamous cell carcinoma (as single agents and in combination). Future
      clinical studies with translational laboratory correlates are necessary to
      determine the roles of retinoids and interferons in the prevention and treatment
      of skin cancer.

PMID- 9627721
TI  - Forty years of control of the oestrous cycle in ruminants: progress made,
      unresolved problems and the potential impact of sperm encapsulation technology.
AB  - Pharmacological control of the oestrous cycle may, with or without sperm
      encapsulation, remain an indispensable part of any attempt to make artificial
      insemination available to the ranch-cattle industry. Of the current methods,
      those most likely to remain acceptable with regulatory agencies and to gain
      acceptance with industry are those involving the short-term use (7-10 days) of
      minimal effective doses of progestins (preferably progesterone) and the
      subsequent use of an analogue of prostaglandin F2 alpha. The use of
      microencapsulated sperm with a long lifespan would allow artificial insemination
      to be achieved without reference to the time when heat and ovulation may occur.

PMID- 9627722
TI  - Oviducal sperm storage in poultry: a review.

PMID- 9627723
TI  - Epididymal constituents and related substances in the storage of spermatozoa: a
      review.
AB  - In vertebrate animals, the duration of storage of viable spermatozoa in the
      epididymis varies from a few hours in birds to many months in reptiles and bats.
      The available information on the unusual composition of the epididymal luminal
      fluid is summarized, and the effect of the various constituents on sperm motility
      is described. Spermatozoa would probably be best stored in an immotile state and
      some constituents of epididymal luminal fluid may be able to inhibit the motility
      of mammalian spermatozoa during storage in vitro. If this effect can then be
      removed at the time of insemination, by changing the spermatozoa to a different
      medium, such a procedure may allow storage of spermatozoa at room or even body
      temperature for extended periods.

PMID- 9627724
TI  - Liquid storage of ram semen: a review.
AB  - Research from 1930 to 1992 is reviewed with regard to storage of semen at reduced
      (0-5 degrees C or 10-15 degrees C) and at ambient temperatures. Diluents
      investigated have included synthetic buffers combined with sugars and egg yolk or
      its fractions, milk from various sources, glycine, and other substances.
      Irrespective of the diluent, dilution rate, temperature or conditions of storage,
      the spermatozoa deteriorate with time of storage. Changes include reduction in
      motility and morphological integrity of spermatozoa, accompanied by a decline in
      their survival in the female reproductive tract, reduction in fertility and
      increased embryonic loss. In critical studies, fertility declined rapidly when
      semen stored for more than 24 h was used for cervical insemination, but after
      intrauterine insemination some spermatozoa maintained their fertilizing capacity
      up to 10 days. Laparoscopic intrauterine or transcervical inseminations could be
      the means of improvement of fertility. These methods may eliminate the problem of
      sperm transport through the cervix and ageing of spermatozoa in the reproductive
      tract, thereby improving fertilization of ova and reducing embryonic loss.

PMID- 9627725
TI  - Lipids and calcium uptake of sperm in relation to cold shock and preservation: a
      review.
AB  - When sperm of the ram, bull, boar and stallion are cold-shocked by rapid cooling
      to near freezing point, motility and metabolic activity are irreversibly
      depressed and the acrosome and plasma membrane disrupted. Ram sperm become
      susceptible to cold shock in the proximal corpus region of the epididymis when
      the cytoplasmic droplet has moved backwards to the distal portion of the sperm
      midpiece. The membrane constituents phospholipids and cholesterol are important
      in cold shock which causes loss of lipid from sperm. The susceptibility of sperm
      to cold shock is linked with a high ratio of unsaturated:saturated fatty acids in
      the phospholipids and a low cholesterol content. The high unsaturated fatty acid
      content of sperm also makes them susceptible to damage from peroxidation which
      adversely affects motility, metabolism, ultrastructure and fertility.
      Hydroxynonenal, a product of fatty acid peroxidation, depresses the motility and
      oxygen uptake of ram sperm in vitro and may react with the -SH groups of the
      axonemal microtubules. High calcium concentrations in the external medium may
      decrease the motility and metabolism of sperm and 'calcium intoxication' may be a
      factor in cold shock. Lowering the environmental temperature increases calcium
      uptake by sperm and the effect is aggravated if the rate of cooling is rapid.
      Phospholipids, particularly those in egg yolk, protect sperm to some extent from
      cold shock and also prevent increased calcium flux into the sperm. Suggestions
      are made for increasing the life span of sperm during preservation and
      microencapsulation by adding agents that may stabilize membranes, counter
      peroxidation and decrease calcium uptake.

PMID- 9627726
TI  - Site of semen deposition and its effect on fertility and sperm retention: a
      review.

PMID- 9627727
TI  - Factors affecting preservation and fertility of bull sperm: a brief review.
AB  - This paper is a brief review of the factors that determine the number of sperm
      required for insemination to obtain high fertility and ways that sperm viability
      might be prolonged. Damage to sperm during freezing results in a requirement,
      after thawing, of about 6 x 10(6) motile sperm (> 10 x 10(6) total) per
      insemination to achieve near-maximal fertility, whereas 2.5 x 10(6) motile fresh
      sperm result in high nonreturn rates. Multiple inseminations to bracket the time
      of ovulation are usually not economical except in superovulated cows. Earlier
      unpublished work on sperm packaging for slow release in the cow and methods for
      stabilizing membranes to increase sperm survival time in the cow are discussed.
      Current studies are directed towards reducing catabolic metabolism of sperm and
      studying membrane changes during freezing and thawing and during incubation with
      bovine oviduct epithelial cells. Studies with bull sperm indicate that the
      choline and ethanolamine phosphoglyceride components of their membranes represent
      an unstable configuration. Exposure of sperm to liposomes with the sterol
      cholesterol can alter the phospholipid bilayer and increase capacitation time.
      Similar approaches may produce sperm with a longer fertilizing life following
      insemination. New procedures in vitro permit low cost modelling of fertilization,
      which will facilitate research by reducing the cost of studies in vivo.

PMID- 9627728
TI  - Maintenance of bioenergetic balance in sperm and prevention of lipid
      peroxidation: a review of the effect on design of storage preservation systems.
AB  - Effective use of encapsulated sperm requires careful review of: (a) the
      conditions under which the procedure can be effectively used; (b) assessment of
      the effect of storage conditions on sperm survival; (c) description of the
      environment of the female tract before, during and after capsule deposition; and
      (d) economic evaluation of impact and costs of the putative technology. Sperm
      survival depends on successful sustenance over two periods of storage (at
      subambient temperatures after collection and extension, then at body temperature
      when placed in the female tract) and one period of action (after release and
      until fertilization). The bioenergetic requirements of cauda epididymal and
      ejaculated bull and ram sperm are reviewed in terms of absolute ATP needs and are
      discussed in terms of storage needs. In addition, sperm inactivation by lipid
      peroxidation is discussed and suggestions are provided to minimize the process.
      Two general types of containers are possible. An open porous form allows free
      passage of nutrients and metabolic products; the entrapped sperm are thus
      subjected to the changing environment in the female tract. The other form is a
      sealed capsule that opens to release sperm before ovulation; it provides a sperm
      storage environment independent of female tract chemistry but introduces problems
      of nutrient supply and metabolite release. Potential experimental approaches to
      evaluate each type of system are discussed.

PMID- 9627729
TI  - The potential impact of sperm encapsulation technology on the importance of
      timing of artificial insemination: a perspective in the light of published work.
AB  - To facilitate artificial insemination with encapsulated spermatozoa independently
      of oestrus, ways must be found to extend the life of spermatozoa at body
      temperature, and to devise encapsulation procedures which will allow progressive
      release of viable spermatozoa over several days. In the past, the most common
      approach to the preservation of semen has been the principle of reduced
      temperature. However, the research literature presents several promising clues to
      the resolution of these problems; these are reviewed, and new directions are
      identified and explored. The potential impact of a successful encapsulation
      technology is recognized as the driving force for implementing the novel research
      required.

PMID- 9627730
TI  - Microencapsulation of bovine spermatozoa for use in artificial insemination: a
      review.
AB  - A technique for microencapsulation of bovine spermatozoa has been developed with
      minimal spermatozoal injury and thus of potential use in artificial insemination.
      The polymers poly-l-lysine, polyvinylamine and protamine sulfate have proven best
      for membranes. Encapsulation has been successful with capsules ranging in size
      from 0.75 to 1.5 mm, and with sperm concentrations from 45 to 180 x 10(6) cells
      mL-1. Successful extenders include CUE, CAPROGEN, and egg yolk-citrate-glycerol
      (maximum 10% v/v egg yolk for normal capsular shape). Capsule fragility (ability
      to rupture under ageing and physical stress) is negatively related to membrane
      thickness which ranges from 1.92 to 5.32 microns (depending on the concentration
      of polymer used) and positively related to concentration of sperm encapsulated.
      Heterospermic studies have shown that encapsulated sperm are capable of
      fertilization in vivo, but are at a disadvantage to unencapsulated sperm when
      cows are inseminated at conventional times. Uterine retention of inseminates is
      favoured by capsules having a 'sticky' membrane. Using current procedures,
      preliminary homospermic fertility studies indicate that sperm encapsulated with
      poly-l-lysine or protamine sulfate may achieve normal fertility.

PMID- 9627731
TI  - Miss-'n-mix and mimics: a new rubrique in this journal.

PMID- 9627732
TI  - Effects of target-controlled anesthesia with propofol and sufentanil on the
      hemodynamic response to Mayfield head holder application.
AB  - The effects of target-controlled anesthesia with propofol and sufentanil on the
      hemodynamic response to Mayfield head holder (MH) application were evaluated in
      18 ASA I and II patients undergoing scheduled intracranial surgery. Premedication
      consisted of hydroxyzine, alprazolam and atropine given orally 1 h before
      surgery. Anesthesia was provided with propofol and sufentanil using a target
      controlled infusion device; constant calculated plasma concentrations of 4
      micrograms ml-1 propofol and 0.5 ng ml-1 sufentanil were maintained throughout
      the study. Muscle relaxation was obtained with atracurium and ventilation was
      controlled with air/oxygen. The MH was fixed 45 +/- 12 min (mean +/- SD) after
      induction of anesthesia. Heart rate and systolic, diastolic, and mean non
      invasive arterial pressure were monitored and recorded 5 min before induction of
      anesthesia (control), 1 min before MH application (MH-1), at MH application, and
      1 and 2 min after MH application. Systolic, diastolic, mean arterial pressure,
      and heart rate increased significantly during and after MH application when
      compared with MH-1 values, but remained constantly lower than control.
      Hemodynamic parameters measured 1 min before MH application were significantly
      lower than control. The results of the study indicate that target-controlled
      anesthesia maintained with constant calculated plasma concentrations of 4
      micrograms ml-1 propofol and 0.5 ng ml-1 sufentanil prevents the increase in
      arterial pressure and heart rate beyond control values following MH application
      but may induce some degree of arterial hypotension in the absence of nociceptive
      stimulation.

PMID- 9627733
TI  - Emergence from target-controlled anesthesia with propofol and sufentanil in
      patients undergoing intracranial surgery.
AB  - The study was designed to characterise the emergence from target-controlled
      anesthesia assessed by the recovery of spontaneous breathing, eye opening to
      command, and extubation in 18 adult patients undergoing intracranial surgery.
      Total intravenous anesthesia was induced and maintained with propofol and
      sufentanil. Target plasma concentration of propofol ranged between 3.0 and 5.5
      micrograms.ml-1 and infusion was stopped after head dressing. The initial target
      plasma sufentanil concentration of 0.50 ng.ml-1 was decreased to 0.15 ng.ml-1
      after craniotomy; sufentanil infusion was discontinued at the dura closure. The
      time from the end of surgery (head dressing) to recovery of spontaneous breathing
      was 8.3 +/- 6.5 min, and the time to eye opening and extubation was 14.7 +/- 10.0
      min. At the end of surgery, the calculated plasma propofol concentration was 3.42
      +/- 0.26 micrograms.ml-1. It significantly decreased to 2.11 +/- 0.51
      micrograms.ml-1 at recovery of spontaneous breathing and to 1.81 +/- 0.41
      micrograms.ml-1 at eye opening and extubation. The calculated plasma sufentanil
      concentration was 0.108 +/- 0.019 ng.ml-1 at the end of surgery but did not
      change significantly between recovery of spontaneous breathing (0.089 +/- 0.013
      ng.ml-1), eye opening and extubation (0.087 +/- 0.013 ng.ml-1). The calculated
      plasma propofol concentrations recorded at emergence were not correlated with
      patient age, total dose of propofol, and duration of infusion; corresponding
      calculated sufentanil concentrations were not correlated with age and total dose
      of sufentanil. An inverse relationship (p < 0.05) was found between the duration
      of sufentanil infusion and the calculated sufentanil concentrations at emergence.
      No correlation was observed between calculated concentrations of propofol and
      sufentanil at emergence.

PMID- 9627734
TI  - Jugular bulb oximetry: review on a cerebral monitoring technique.
AB  - Jugular bulb oximetry is the first available continuous monitoring method
      estimating the adequacy of cerebral perfusion. Despite its major technical as
      well as methodological shortcomings the information on the oxygen supply to
      demand balance of the brain seems most valuable. Especially the deleterious
      consequences of systemic variations (mainly concerning arterial blood pressure
      and CO2-tension) on the diseased brain are revealed by jugular bulb saturation
      values. The prevention and/or the early detection of these systemic secondary
      insults could have important implications as to final neurological outcome.
      Jugular bulb oximetry could also guide specific intracranial antihypertensive
      treatment, as it may reveal the pathophysiological mechanisms behind intracranial
      hypertension with regard to the status of cerebral perfusion (cerebral hyperemia
      or cerebral hypoperfusion). These insights might increase the efficacy of all
      treatments available for intracranial hypertension.

PMID- 9627735
TI  - Bilateral mydriasis during laparoscopic surgery.
AB  - Peritoneal insufflation with CO2 has been associated with profound
      cardiorespiratory disturbances, which may modify cerebral blood flow (CBF),
      particularly in hypertensive patients in whom CBF autoregulation is altered. We
      report a case of bilateral mydriasis during laparoscopic gastrectomy in a patient
      with chronic hypertension followed by a coma lasting several hours and we shortly
      discuss the possible mechanisms involved.

PMID- 9627736
TI  - Coronary artery spasm during anesthesia for liver resection.
AB  - Intraoperative coronary artery spasm (CAS) is rare, and most cases have been
      reported during cardiac surgery (4, 7, 12). The following is a case report of a
      patient undergoing liver resection developing CAS, resulting in well-documented
      ST-segment elevation in lead II and V5 of the electrocardiogram (ECG) and severe
      hemodynamic instability. The coronary spasm was successfully treated with
      intravenous nitroglycerin. Postoperatively, a coronary angiogram documented CAS
      in the absence of significant coronary artery disease, confirming the clinical
      diagnosis of CAS.

PMID- 9627737
TI  - Recommendations on pre-anesthetic evaluation of patients put forward jointly with
      the BSAR and the BPASAR. The Belgian Society of Anesthesia and Reanimation and
      the Belgian Professional Association of Specialists in Anesthesia and
      Reanimation.

PMID- 9627738
TI  - Whither vitamin E and tardive dyskinesia?

PMID- 9627739
TI  - Vitamin E, lipids, and lipid peroxidation products in tardive dyskinesia.
AB  - BACKGROUND: Lipid peroxidation has been postulated as a possible mechanism for
      neuronal damage in tardive dyskinesia, and this is supported by evidence of
      increased lipid peroxidation products in the cerebrospinal fluid of dyskinetic
      subjects. METHODS: In this study plasma levels of vitamin E and vitamin A,
      measured by high-performance liquid chromatography, and of thiobarbituric acid
      reactive substances (TBARS), were determined in 16 schizophrenic patients with
      tardive dyskinesia, 16 nondyskinetic patients all assessed by Abnormal
      Involuntary Movement Scale (AIMS), and 10 normal control subjects. Plasma
      cholesterol and triglyceride were also measured throughout. Vitamin E levels in
      plasma were corrected for total lipids. RESULTS: Multivariate analysis of
      covariance showed significant differences when vitamin E and TBARS were compared
      in the three groups. Univariate t tests showed a significantly lower lipid
      corrected vitamin E (p = .018) between the normal and dyskinetic group but not
      between the normal and the nondyskinetic schizophrenic patients. There was no
      difference in vitamin A levels between patients and normal controls. TBAR results
      showed a significant positive correlation between AIMS score and lipid-corrected
      TBARS. CONCLUSIONS: This study confirms an abnormality associating lipid
      peroxidation and tardive dyskinesia and extends this abnormality to measurements
      of lipid-corrected vitamin E in plasma.

PMID- 9627740
TI  - Long-term treatment effects of vitamin E for tardive dyskinesia.
AB  - BACKGROUND: Several studies have found that alpha-tocopherol (vitamin E) can
      effectively treat tardive dyskinesia (TD). A limitation of these trials is their
      short treatment durations (maximum of 12 weeks), which do not allow us to address
      the effects of long-term treatment. METHODS: To participate, patients had to have
      TD and be on stable oral medications. The study enrolled 40 patients who received
      up to 36 weeks of treatment with d-vitamin E (1600 IU per day) or placebo.
      RESULTS: Using the Abnormal Involuntary Movements Scale (AIMS) score (sum of
      items #1-7) to measure TD severity, the study found a significant difference (3
      points) in mean AIMS scores, in favor of vitamin E, starting at 10 weeks of
      treatment and continuing through the full 36 weeks. We used linear mixed-effects
      regression to quantify the impact of several covariates, and found that treatment
      assignment. TD duration, and chlorpromazine equivalents had significant effects
      on decreasing the AIMS score. CONCLUSIONS: The study's finding that vitamin E is
      effective in treating TD agrees with results from prior studies and provides
      evidence that the effect may extend to treatment of up to 36 weeks. These
      findings are in direct contrast to those of VA Cooperative Study #394, a much
      larger, long-term, multi-site study, conducted by many of the same investigators,
      in which Vitamin E was not superior to placebo.

PMID- 9627741
TI  - Is P50 suppression a measure of sensory gating in schizophrenia?
AB  - BACKGROUND: Abnormal P50 response has been hypothesized to reflect the sensory
      gating deficit in schizophrenia. Despite the extensive literature concerning the
      sensory filtering or gating deficit in schizophrenia, no evidence has been
      provided to test the relationship of the P50 phenomenon with patients'
      experiences of perceptual anomalies. METHODS: Sixteen drug-free DSM-IV diagnosed
      schizophrenic patients who reported moderate to severe perceptual anomalies in
      the auditory or visual modality were examined as compared to 16 schizophrenic
      patients who did not report perceptual anomalies, and 16 normal subjects. Both
      control groups were age- and gender-matched with the study group. RESULTS:
      Patients reporting perceptual anomalies exhibited P50 patterns that did not
      differ from normal subjects. In contrast, patients who did not report perceptual
      anomalies showed the abnormal P50 ratios previously found to be associated with
      schizophrenia. CONCLUSIONS: These paradoxical findings do not support the
      hypothetical relationship between the P50 and behavioral measures of sensory
      gating, suggesting that additional studies are needed to further explore the
      clinical correlates of the P50.

PMID- 9627742
TI  - Association between regional brain volumes and clozapine response in
      schizophrenia.
AB  - BACKGROUND: Clozapine has shown considerable therapeutic promise in the treatment
      of schizophrenia; however, the clinical risks and initial high treatment costs
      associated with its administration motivate the search to identify patients who
      will best respond. Neuroimaging studies have suggested that prefrontal sulcal
      prominence may be a predictor of nonresponsiveness. METHODS: We used magnetic
      resonance imaging (MRI) to test whether volumes in any cortical regions of the
      brain were associated with symptom improvement with clozapine treatment. The 21
      schizophrenic men studied were clinically evaluated during treatment with typical
      neuroleptics (baseline) and after a mean of 6.2 months treatment with clozapine
      (final dose 300-900, median = 562 mg/day). At least a 20% improvement on total
      Brief Psychiatric Rating Scale (BPRS) was seen in 47.6% of the schizophrenics.
      Clinical improvement was regressed on baseline differences in clinical severity,
      and the residual scores were related to MRI values. RESULTS: Patients with larger
      anterior superior temporal lobe cerebrospinal fluid volumes (primarily sylvian
      fissure) showed greater improvement on total BPRS and withdrawal/retardation
      symptoms. CONCLUSIONS: Even schizophrenics with significant brain dysmorphology
      can have a positive clinical response to clozapine.

PMID- 9627743
TI  - Leukocyte differentials predict short-term clinical outcome following
      antipsychotic treatment in schizophrenia.
AB  - BACKGROUND: The majority of patients with schizophrenia and many of their
      unaffected siblings exhibit a relative granulocytosis and lymphopenia. To
      characterize these abnormalities better, we examined leukocyte differentials and
      organ nonspecific autoantibodies in relationship to intake phenomenology and
      short-term clinical outcome. METHODS: We studied patients with schizophrenia (n =
      81) and their siblings (n = 18). At intake assessment, about one-half of the
      probands (n = 38) were neurolepticnaive first-episode patients; the remainder
      were medication-free for at least 2 weeks. Hematologic indices were obtained at
      intake assessment, and psychiatric symptomatology was assessed at baseline and
      following 6 months of clinically determined treatment. RESULTS: A relative
      granulocytosis and lymphopenia prospectively predicted poorer recovery in
      positive, but not negative, symptoms after 6 months of antipsychotic treatment.
      Abnormal leukocyte proportions were specific to patients who presented with
      clinically significant positive symptomatology at intake. In contrast, clinically
      significant negative symptoms were only evident in a small subgroup of patients
      who were positive for antinuclear autoantibodies and/or rheumatoid factor.
      CONCLUSIONS: Future research should further test the hypothesis that a relative
      granulocytosis and lymphopenia reflect genetic loading for the pathophysiologic
      determinants of positive symptoms. Future research also should determine the
      etiologic significance of organ nonspecific autoimmunity in predominantly
      negative symptom schizophrenia.

PMID- 9627744
TI  - Pituitary-adrenal hormones and testosterone across the menstrual cycle in women
      with premenstrual syndrome and controls.
AB  - BACKGROUND: Premenstrual syndrome (PMS) is a cyclic mood disorder, widely
      believed, yet not conclusively shown, to be of endocrine etiology. This study
      examines basal levels of several hormones reported, albeit inconsistently, to
      differ in women with PMS compared with controls. METHODS: Subjects (10 PMS
      patients and 10 controls) had their blood drawn for one full menstrual cycle.
      Subjects' mood and behavioral symptoms were assessed by daily self-ratings and
      objective ratings. Plasma was assayed for total and free testosterone (T), beta
      endorphin (beta-EP), adrenocorticotropic hormone (ACTH), and cortisol. RESULTS:
      No differences were observed between the PMS and control groups for beta-EP,
      ACTH, or cortisol. PMS subjects had significantly lower total and free T plasma
      levels with a blunting of the normal periovulatory peak, a finding that may be
      epiphenomenal to age. CONCLUSIONS: This study does not confirm previous reports
      of abnormalities in plasma levels of either ACTH or beta-EP in women with PMS; it
      also fails to replicate a previous observation of high free T levels in women
      with PMS. These results are not supportive of a primary endocrine abnormality in
      PMS patients.

PMID- 9627745
TI  - Serotonin reuptake antidepressant effects on sexual function in patients with
      anxiety disorders.
AB  - BACKGROUND: Serotonin reuptake inhibitor (SRI) antidepressants have been
      associated with sexual dysfunction, though there have been few prospective
      reports specifically examining this problem. The purpose of this study was to
      determine if three SRIs affected sexual function in anxiety disorder patients
      over a 3-month period. METHODS: Thirty-one patients were enrolled in a
      prospective study of the effect of three SRIs, fluoxetine, sertraline, and
      paroxetine, on five aspects of sexual function: libido, erection/lubrication,
      orgasm quality, orgasm delay, and sexual frequency. Measurements were made at
      baseline and at each month on visual analogue scales. RESULTS: For men and women,
      orgasm quality was lower and orgasm delay longer at months one, two, and three
      compared to baseline (p < .01). Erection scores were lower over time, but this
      change was not statistically significant. Lubrication, libido, and sexual
      frequency were not appreciably changed over 3 months. A higher rate of anorgasmia
      was noted in women at months one and two, but this did not achieve significance.
      CONCLUSIONS: Orgasm appears to be a primary sexual function affected by SRIs.

PMID- 9627746
TI  - Serotonin transporter gene variants in alcohol-dependent subjects with dissocial
      personality disorder.
AB  - BACKGROUND: We tested the hypothesis that a functional biallelic repetitive
      element in the 5' regulatory region of the human serotonin transporter gene
      (SLC6A4) confers susceptibility to serotonin-related personality traits
      underlying alcohol dependence with dissocial behavior. METHODS: The association
      study was focused on 64 alcohol-dependent subjects with a dissocial personality
      disorder (according to ICD-10) who were derived from 315 German alcohol-dependent
      subjects. The Tridimensional Personality Questionnaire (TPQ) was applied to
      assess personality dimensions in 101 alcohol-dependent men, including 39
      dissocial alcoholics. RESULTS: Our association analyses revealed a trend towards
      a higher frequency of the short (S) allele of the SLC6A4 polymorphism in
      dissocial alcoholics compared to 216 German controls (chi 2 = 2.81, df = 1, p =
      0.094). Dissocial alcoholics carrying the S/S genotype exhibited significant
      lower scores of harm avoidance compared to those lacking it (U-test, p = 0.015).
      Significantly higher novelty seeking scores were obtained in dissocial alcoholics
      carrying the S allele relative to those lacking it (U-test, p = 0.021).
      CONCLUSIONS: Our tentative association findings in dissocial alcoholics suggest
      that the S allele of the 5' regulatory SLC6A4 polymorphism confers susceptibility
      to a temperamental profile of high novelty seeking and low harm avoidance that
      has been postulated to underlie dissocial (type-2) alcoholism according to
      Cloninger's neurogenetic theory of personality.

PMID- 9627747
TI  - Depression in Parkinson's disease is not accompanied by more corticotropin
      releasing hormone expressing neurons in the hypothalamic paraventricular nucleus.
AB  - BACKGROUND: Depression is frequently encountered in Parkinson's disease (PD). In
      addition, more than half of the PD patients have a disturbed dexamethasone
      suppression test, which is associated with increased activity of corticotropin
      releasing hormone (CRH) neurons. We recently found an increase in CRH neuron
      number, CRH-messenger RNA, and vasopressin colocalization in CRH neurons in the
      paraventricular nucleus (PVN) of depressed patients, which may be involved in the
      pathogenesis of depression. METHODS: The number of neurons expressing CRH was
      determined in the PVN of 6 depressed PD patients with a high score (> or = 13) on
      the Hamilton Depression Rating Scale, 6 nondepressed PD patients, and 6 controls.
      RESULTS: The three groups did not differ in the number of neurons expressing CRH.
      CONCLUSIONS: We hypothesize that activation of CRH neurons in the PVN, as we
      recently observed in idiopathic depression, does not play an essential role in
      depression in PD.

PMID- 9627748
TI  - The "incredible shrinking" P50 event-related potential.
AB  - The P50 component of the auditory evoked response has been utilized in studies of
      sensory gating in schizophrenia for over 15 years. As P50 gating studies have had
      a greater impact in neuroscience research, investigators have refined several key
      variables (e.g., filtering) to enhance signal-to-noise ratios. A comprehensive
      review of P50 reports suggests P50 amplitude has been steadily decreasing over
      the years. Certain methodological "advances" are suggested as key reasons for
      this apparent reduction in P50 amplitude. Gating studies continue to yield
      interesting findings in neuropsychiatric research, especially when ratio vs.
      absolute difference scores are used.

PMID- 9627749
TI  - Selection of digital filtering parameters and P50 amplitude.

PMID- 9627750
TI  - Transient frontal hypoperfusion in Tc-99m hexamethylpropyleneamineoxime single
      photon emission computed tomography imaging during alcohol withdrawal.
AB  - BACKGROUND: Regional brain perfusion in patients during alcohol-withdrawal has
      been relatively less studied with brain SPECT technique. In this study, the
      hypothesis that possible regional cerebral blood flow (rCBF) alterations due to
      alcohol withdrawal might be transitory in a homogenous group of alcoholic
      patients in terms of their physical-nutritional and cognitive functional
      conditions was investigated. METHODS: Fifteen right-handed male inpatients with
      alcohol-withdrawal, diagnosed according to DSM-IIIR criteria, and 6 male
      physically-mentally healthy control subjects were included in the study. The
      first Technetium 99m-hexamethylpropyleneamineoxime (Tc-99m-HMPAO) brain SPECT
      investigation was performed on the day of admission in nonmedicated conditions
      and the second one was performed after all the withdrawal symptoms had subsided
      in the patients. As an indicator of the change in the brain perfusion, a relative
      perfusion index was used and the relative tracer activity was expressed as the
      ratio of mean cortical region of interest activity to mean the whole cortical
      brain activity. RESULTS: We found significantly reduced left frontal and right
      frontal, parietal and temporal rCBF values in the patients during the alcohol
      withdrawal compared to those of their remitted state while they were not
      different from in the control group (p < 0.05). CONCLUSIONS: Our data indicate
      that the alterations in rCBF during the alcohol-withdrawal are more pronounced
      both in the frontal cortex and in overall right hemisphere regions. Furthermore,
      the frontal hypoperfusion may be transitory with recovery from alcohol-withdrawal
      whereas temporal hypoperfusion may continue after recovery probably depending on
      the previously administered high-dose benzodiazepines.

PMID- 9627751
TI  - Interaction of serotonin reuptake inhibitor and 3,4
      methylenedioxymethamphetamine?

PMID- 9627752
TI  - Sertraline discontinuation syndrome presenting with severe depression and
      compulsions.

PMID- 9627753
TI  - Physics and technology of cardiovascular MR imaging.
AB  - MR imaging has made rapid progress and promises to be of great utility in the
      evaluation of the cardiovascular system. Some of the features that make it so
      promising are its safety (with appropriate guidelines); its ability to produce
      high-quality tomographic images in arbitrary orientations; and the possibility to
      obtain unique data, such as on regional myocardial function and metabolism.
      Ongoing technical developments in such areas as more rapid imaging and newer
      contrast agents should continue to increase the usefulness of cardiovascular MR
      imaging.

PMID- 9627754
TI  - Imaging cardiac structure and pump function.
AB  - This article describes magnetic resonance imaging approaches for assessing
      cardiac structure and myocardial pump function. The article is divided into
      cardiac structure and ventricular function. Throughout, representative images are
      included. There are numerous applications of magnetic resonance imaging for
      assessing cardiac structure and function, and magnetic resonance imaging compared
      favorably to other imaging modalities.

PMID- 9627755
TI  - MR blood flow measurement. Clinical application in the heart and circulation.
AB  - Several magnetic resonance imaging methods for measuring blood flow have greatly
      enhanced the capability of magnetic resonance imaging as a physiologic tool in
      cardiology. This article concentrates on phase-related techniques. Magnetic
      resonance velocity mapping is a flexible, robust, and accurate method of
      obtaining functional information in the cardiovascular system. It has the
      potential to contribute significantly to clinical decision making, and it should
      be a routine part of cardiovascular imaging whenever information on flow is
      required.

PMID- 9627756
TI  - Regional myocardial function.
AB  - Methods for noninvasive tissue tracking and quantification of myocardial
      shortening with magnetic resonance imaging have been developed using
      presaturation tagging and velocity encoded phase maps. The concurrent development
      of rapid scanning techniques, such that a complete cine loop of a slice can be
      obtained in a breath-hold, has made the measurement of myocardial wall motion in
      patients a simple and reproducible examination. These methods make it possible to
      quantify the severity and extent of regional heart wall motion abnormalities both
      at rest and during stress.

PMID- 9627757
TI  - Coronary MR angiography.
AB  - Coronary MR angiography is a new noninvasive diagnostic method in rapid
      evolution. It has the potential to combine structural information with functional
      assessment of coronary blood flow. Advances in technology will undoubtedly lead
      to enhanced resolution, improved accuracy, and shorter scan times. It is certain
      that coronary MR angiography will be a prominent diagnostic clinical tool in the
      years to come.

PMID- 9627758
TI  - Assessing myocardial perfusion in coronary artery disease with magnetic resonance
      first-pass imaging.
AB  - MRFP perfusion imaging can now be used clinically on most MR scanner systems (1.0
      to 1.5 T). The current experimental data demonstrate that MRFP imaging allows the
      quantitative assessment of myocardial blood flow changes and accurate
      measurements of collateral flow, including changes in the collateral dependent
      zones. Certain protocols, however, as outlined here have to be followed to obtain
      all the possible diagnostic information. Based on the current data on MRFP
      imaging, it is realistic to anticipate that MRFP imaging in combination with cine
      or tagging MR imaging will provide clinicians with better methods to distinguish
      stunned and hibernating, from nonviable myocardium and obtain better outcome
      data. Dedicated MR scanners are now being designed to meet the needs for MR
      imaging of patients with coronary artery disease. These scanners, small in size
      and with better patient access, make placement near the coronary care unit or
      catheterization laboratory feasible. This is a major step toward enhancing the
      utility of this new technique by providing the necessary infrastructure for
      scanning large numbers of patients. The main obstacle to wider use of these new
      diagnostic tools to assess perfusion is the lack of a large clinical database
      because there have not yet been major multicenter trials. With the development of
      novel intravascular contrast agents, however, larger trials are planned that
      should provide the clinical data mandatory for full integration of MRFP imaging
      into clinical practice. In particular, the development of dedicated and user
      friendly perfusion analysis software will create the means to evaluate MR
      perfusion data accurately in large patient populations. These studies need to be
      conducted in a collaborative fashion by cardiologists, heart surgeons, and
      radiologists to be fully accepted by health care providers in an increasingly
      cost-averse and competitive health care environment.

PMID- 9627760
TI  - Integrated approach to ischemic heart disease. The one-stop shop.
AB  - Magnetic resonance imaging is unique in its variety of applications for imaging
      the cardiovascular system. A thorough assessment of myocardial structure,
      function, and perfusion; assessment of coronary artery anatomy and flow; and
      spectroscopic evaluation of cardiac energetics can be readily performed by
      magnetic resonance imaging. One key to the advancement of cardiac magnetic
      resonance imaging as a clinical tool in the evaluation, the so called one stop
      shop. Improvements in magnetic resonance hardware, software, and imaging speed
      now permit this integrated examination. Cardiac magnetic resonance is a powerful
      technique with the potential to replace or complement other commonly used
      techniques in the diagnostic armamentarium of physicians caring for patients with
      ischemic heart disease.

PMID- 9627759
TI  - MR of the heart under pharmacologic stress.
AB  - Magnetic resonance imaging is one method for assessing cardiac function and
      perfusion at rest and under stress conditions. In this article, the potential of
      stress magnetic resonance imaging for evaluating ischemic heart disease is
      reviewed, and technical aspects of some developments that may contribute to
      comprehensive magnetic resonance imaging assessment of heart disease under rest
      and stress are discussed.

PMID- 9627761
TI  - Integrated MR imaging approach to valvular heart disease.
AB  - With development of cine and velocity encoded magnetic resonance imaging, it is
      now feasible to detect and quantify aortic and mitral stenosis and regurgitation
      accurately. In addition, magnetic resonance imaging has the capabilities to
      assess simultaneously left and right ventricular mass, volumes, and function
      precisely. The high accuracy and reproducibility of magnetic resonance imaging in
      quantification of regurgitation and ventricular function has the potential to
      provide improved monitoring of therapy and optimal timing of surgery in patients
      with valvular dysfunction. In comparison to echocardiography and angiography,
      some current limitations of magnetic resonance imaging to an integrated approach
      of valvular heart disease exist, which may be removed with future refinement of
      magnetic resonance imaging technology for cardiovascular imaging.

PMID- 9627762
TI  - Diseases of the aorta.
AB  - The medical community has begun to realize the complexity of aortic pathology in
      vivo and its often iridescent and ambiguous clinical presentation. Diagnostic
      modalities such as transesophageal echocardiography, magnetic resonance imaging,
      and computed tomography have all been shown to be useful to investigate the
      aorta, both in chronic disease and in acute aortic syndromes. This article
      focuses on the possibilities and emerging advantages of magnetic resonance
      imaging with respect to a spectrum of aortic pathologies.

PMID- 9627763
TI  - Cardiac MR imaging in congenital heart disease.
AB  - Magnetic resonance imaging is a unique and insightful tool for the assessment of
      structure and function in congenital heart disease. For anatomic assessment, the
      large field of view, lack of limitation by patient size, and ability to create
      three-dimensional surface displays from routine imaging acquisitions offer
      several advantages over other modalities. The ability of magnetic resonance
      imaging to assess the volume and mass of bizarre ventricular shapes accurately
      and myocardial tissue and blood tagging as well as phase encoded velocity mapping
      has enhanced research in pediatric cardiology. Newer techniques, such as oxygen
      sensitive magnetic resonance imaging and echo-planar magnetic resonance imaging,
      promise even further advances in research and in clinical applications.

PMID- 9627764
TI  - Assessment of the visceral afferent and autonomic pathways in response to
      esophageal stimulation in control subjects and in patients with diabetes.
AB  - OBJECTIVE: To examine the effects of esophageal stimulation on vagal afferent and
      efferent pathways in volunteers without diabetes and patients with diabetes.
      DESIGN: Prospective physiological study. PARTICIPANTS: Fourteen control subjects
      without diabetes and 6 patients with diabetes. INTERVENTIONS: Electrical and
      mechanical stimulation of the esophagus. OUTCOME MEASURES: Cortical evoked
      potentials and the power spectra of heart rate variability. RESULTS: For the
      control subjects, there was a significant decrease in the ratio of the low
      frequency to high frequency (LF:HF) power (i.e., increased vagal efferent
      modulation) during stimulation. Reproducible cortical evoked potentials were
      obtained from all control subjects. In the 6 patients with diabetes, who had
      viscerosensory and autonomic neuropathy, the cortical evoked potentials showed an
      erratic non-reproducible response to electrical esophageal stimulation; however,
      the LF:HF ratio decreased in these patients during stimulation, suggesting an
      intact subcortical reflex circuit. CONCLUSIONS: Vago-afferent fibres can be
      studied using minimally invasive techniques, and the power spectral analysis of
      heart rate variability permits study of autonomic vago-efferent pathways.

PMID- 9627765
TI  - Aspartylglucosaminuria in a Canadian family.
AB  - Aspartylglucosaminuria (McKusick 208400) is a lysosomopathy associated with
      aspartylglucosaminidase (L-aspartamido-beta-N-acetylglucosamine amidohydrolase,
      EC 3.5.1.26) deficiency. It has been most frequently encountered in Finland,
      where the regional incidence may be as high as 1 in 3600 births. In North America
      it is very rare, having been reported in only 8 patients. We encountered 4
      patients with aspartylglucosaminuria in a Canadian family of 12 siblings. The 4
      siblings affected--2 brothers and 2 sisters--were apparently normal at birth;
      however, their developmental milestones, particularly speech, were slow, and they
      acquired only a simple vocabulary. Throughout life, there was a progressive
      coarsening of facial features; 3 had inguinal hernia and recurrent diarrhea; all
      became severely retarded and by the 4th decade showed evident deterioration of
      both cognitive and motor skills; 2 exhibited cyclical behavioural changes. Three
      of the siblings have died, at 33, 39 and 44 years of age. Two died of
      bronchopneumonia and 1 of asphyxiation following aspiration. In the urine of all
      4 siblings, and in the 1 liver examined, we found 2-acetamido-1-N-(4-L-aspartyl)
      2-deoxy-beta-D-glucosamine (GlcNAc-Asn) and alpha-D-mannose-(1,6)-beta-D-mannose
      (1,4)-2-acetamido- 2-deoxy-beta-D-glucose-(1,4)-2-acetamido-1-N-(4-L-aspartyl)-2
      deoxy-beta - D-glucosamine (Man2-GlcNAc2-Asn). Compared with the level of
      activity in controls, aspartylglucosaminidase activity was less than 2% in
      fibroblasts from 3 of the siblings, less than 0.5% in leukocytes from 1 sibling,
      and less than 1% in the liver of 1 sibling, whereas other acid hydrolase
      activities in these tissues were normal. Ultrastructural studies of skin showed
      that fibroblasts, endothelial cells and pericytes contained vacuoles with fine
      reticulo-floccular material. Glial and neuronal cells of the central nervous
      system showed similar inclusions as well as others composed of concentric or
      parallel membranous arrays intermingled with lipid droplets.

PMID- 9627766
TI  - Radiotherapy for breast cancer in Ontario: rate variation associated with region,
      age and income.
AB  - OBJECTIVE: To describe the variation in the use of radiotherapy (RT) in women in
      Ontario within 1 year of diagnosis of breast cancer, from 1982 to 1991, and to
      identify factors associated with these variations. DESIGN: Retrospective,
      population-based cohort study. SETTING: Ontario. POPULATION: All women registered
      by the Ontario Cancer Registry (OCR) with a diagnosis of invasive breast cancer
      between Jan. 1, 1982, and Dec. 31, 1991. INTERVENTIONS: RT to any anatomic site
      within 1 year of the diagnosis of breast cancer. OUTCOME MEASURES: Odds of
      receiving RT within 1 year of diagnosis (from RT files from all radiotherapy
      departments in Ontario) associated with year and with geographic, age-related and
      socioeconomic factors. RESULTS: Use of RT within 1 year of diagnosis increased
      from 21.1% (95% confidence interval [CI] 19.8-22.4) in 1982 to 44.7% (95% CI 43.4
      46.0) in 1991 (p < 0.0001). Among the regions of Ontario, the use of RT varied
      from 24.5% (95% CI 23.5-25.6) to 44.4% (95% CI 43.0-45.9) (p < 0.0001).
      Increasing age was associated with decreasing likelihood of receiving RT (test
      for trend p < 0.0001), as was decreasing income (test for trend p < 0.0001).
      CONCLUSIONS: The use of RT within 1 year of the diagnosis of breast cancer in
      women in Ontario varies by region, age and income. Despite universal and
      comprehensive health insurance coverage, women with breast cancer in some
      populous regions of Ontario were less likely to receive RT within 1 year of their
      diagnosis than women in other populous regions.

PMID- 9627767
TI  - Postprandial dyspnea and malnutrition in patients with chronic obstructive
      pulmonary disease.
AB  - OBJECTIVE: To compare ventilatory response, oxygen uptake and sense of dyspnea of
      underweight versus normal-weight patients with chronic obstructive pulmonary
      disease (COPD) after a standard meal, in order to investigate whether an increase
      in dyspnea due to diet-induced thermogenesis might lead to altered eating habits.
      Weight loss in patients with COPD leads to adverse health effects, but the
      reasons for this loss are not well understood. DESIGN: Prospective study.
      PARTICIPANTS: A total of 18 patients (14 men, 4 women) aged 46 to 83 with severe,
      stable COPD. OUTCOME MEASURES: Minute ventilation (VE), tidal volume (VT),
      frequency of breathing, oxygen uptake (VO2), carbon dioxide excretion (VCO2) and
      sense of dyspnea (using the Borg scale) were measured 15 minutes before a 2.5-MJ
      (600-kcal) balanced liquid meal and at four 15-minute intervals after the meal.
      RESULTS: Increases in VE, VT, VO2 and VCO2 were observed for all subjects.
      Corrected for body surface area, the maximum postprandial changes in these
      indicators did not differ between the underweight and the normal-weight subjects
      with COPD. Work of breathing (measured in 11 subjects) did not differ between the
      2 groups, nor did the number of subjects reporting increased dyspnea.
      CONCLUSIONS: Since the increases in VE, VO2, VCO2 and perceived dyspnea did not
      differ between the normal-weight and underweight patients, this indicates that
      dyspnea at mealtimes is not likely to lead to decreased food intake.

PMID- 9627768
TI  - Felodipine extended release versus conventional diuretic therapy for the
      treatment of systolic hypertension in elderly patients. The National Trial Group.
AB  - OBJECTIVE: To compare 8 weeks of monotherapy using either felodipine extended
      release (ER) or a conventional diuretic therapy, triamterene/hydrochlorothiazide
      (HCTZ), in elderly patients with systolic hypertension. DESIGN: Prospective,
      randomized, single-blind screening, double-blind treatment, parallel group
      comparison. SETTING: Twenty-nine general and family practice sites across Canada.
      PARTICIPANTS: Men and post-menopausal women aged 60 to 85 years, with mild to
      moderate primary systolic hypertension (systolic blood pressure > 160 mm Hg or
      blood pressure > 140/ > 90 mm Hg). INTERVENTIONS: Daily doses of either
      felodipine ER (2.5 mg) or triamterene/HCTZ (25/12.5 mg) for 8 weeks. After the
      first 4 weeks, the patients who responded to the initial dosage (a reduction in
      systolic blood pressure of at least 15 mm Hg) or whose blood pressure was
      controlled on the dosage (systolic blood pressure < 140 mm Hg) continued to take
      the low dose. Among the others, the daily doses were doubled for the final 4
      weeks. OUTCOME MEASURES: Systolic blood pressure before beginning treatment and
      at the end of the study, as well as adverse events and results of heart rate
      measurement, clinical chemistry tests, electrocardiograms and physical
      examinations before and after therapy. RESULTS: Sufficient data for analysis were
      obtained from 216 patients (86 men and 130 women). Mean seated blood pressure was
      reduced significantly in both the felodipine group (from 168/91 to 151/84 mm Hg)
      and the diuretic group (from 168/92 to 147/84 mm Hg). The difference in mean
      reductions in systolic blood pressure between the groups was 2.2 mm Hg (with a
      95% confidence interval of-1.7 to 6.0 mm Hg), which was not significant. Clinical
      chemistry measurements taken before treatment and at the end of the study showed
      that more patients in the diuretic group developed abnormal values for blood urea
      nitrogen, uric acid and creatinine. Other changes were unremarkable. The
      incidence of adverse events was similar in both groups, but more patients in the
      felodipine group (9) than in the diuretic group (3) discontinued treatment owing
      to an adverse event. CONCLUSIONS: Felodipine ER (2.5 to 5 mg daily) is as
      effective in reducing systolic blood pressure as triamterene/HCTZ (25/12.5 mg to
      50/25 mg daily). More patients discontinued felodipine treatment than
      triamterene/HCTZ treatment owing to adverse events. However, patients receiving
      triamterene/HCTZ tended to have abnormal levels in clinical chemistry tests;
      these should be monitored.

PMID- 9627770
TI  - Funding biomedical, clinical and health research in Canada.

PMID- 9627769
TI  - Cobalamin metabolism in methionine-dependent human tumour and leukemia cell
      lines.
AB  - OBJECTIVE: To identify the defect in cobalamin metabolism in the human melanoma
      cell line MeWoLC1, and to determine how frequent this defect is in other
      methionine-dependent tumour cell lines. DESIGN: Biochemical and somatic cell
      genetics study. INTERVENTIONS: Aspects of cobalamin metabolism were measured in a
      panel of 14 human tumour cell lines that were unable to proliferate normally in
      medium in which methionine had been replaced by its metabolic precursor
      homocysteine (methionine-dependent cell lines). RESULTS: The human melanoma cell
      line MeWoLC1 was unique among these cell lines, in that it was characterized by
      decreased uptake of cobalamin, decreased synthesis of coenzyme derivatives, and
      decreased functional activity of the cobalamin-dependent enzymes methionine
      synthase and methylmalonylCoA mutase. This phenotype was identical to that
      observed in fibroblasts from patients with the cblC and cblD inborn errors of
      cobalamin metabolism. The defect in cobalamin metabolism in MeWoLC1 was
      complemented in somatic cell complementation analysis by cblA, cblB, cblD, cblE
      and cblG fibroblasts, but not by cblC fibroblasts, strongly suggesting that the
      defect in this cell line affects the cblC locus. Similar changes in cellular
      cobalamin metabolism were not seen in any other methionine-dependent cell line in
      the panel, suggesting that there may be multiple causes of methionine dependence,
      and that inactivation of the cblC locus may not be a common cause of this
      phenotype in transformed cells. CONCLUSIONS: The defect underlying methionine
      dependence in MeWoLC1 appears to involve the locus that is affected in patients
      with the cblC inborn error of metabolism. This defect does not seem to be common
      among other methionine-dependent cell lines.

PMID- 9627771
TI  - Why autologous tissue?
AB  - Breast reconstruction with autologous tissue achieves more natural results and a
      better simulation of a real breast than reconstruction based on prosthetic
      implants. Unlike implant-based reconstructions, which tend to develop capsular
      contractures, the results of autologous tissue reconstruction tend to improve
      with time. In the long run, the costs of autologous breast reconstruction with
      transverse rectus abdominis myocutaneous (TRAM) flaps are equal to or lower than
      those of reconstruction with tissue expansion and implants. Consequently,
      autologous tissue is preferable for most patients, provided they are suitable
      candidates for the surgery required by autologous reconstruction.

PMID- 9627772
TI  - Immediate breast reconstruction.

PMID- 9627773
TI  - Delayed breast reconstruction.
AB  - Immediate reconstruction is becoming increasingly popular because it gives a
      better aesthetic result for breast reconstruction, and is more economical and
      convenient for patients than delayed reconstruction. Delayed breast
      reconstructions are still needed in 80% of mastectomized patients under 40 years
      and in half the women under 54 years--at least in Finland. This article discusses
      the technique of and contraindications for the free transverse rectus abdominis
      myocutaneous (TRAM) flap technique based on the author's experience with over 300
      free TRAM operations. The pedicled TRAM and the deep inferior epigastric artery
      (DIEA) perforator flap are also discussed.

PMID- 9627774
TI  - Breast reconstruction with a pedicled TRAM flap.
AB  - Breast reconstruction with the pedicled transverse rectus abdominis myocutaneous
      (TRAM) flap remains a useful option for most patients seeking autogenous tissue
      reconstruction. This article emphasizes aesthetic analysis of the opposite breast
      and tissue requirements as important determinants of the preoperative
      reconstructive plan and guides for specific procedure selection (unipedicle
      versus bipedicle). This article succinctly reviews the techniques and tips for
      flap elevation and inset, designed to produce consistent aesthetic outcomes with
      pedicled TRAM flap breast reconstruction.

PMID- 9627776
TI  - The free TRAM flap.
AB  - The transverse rectus abdominis myocutaneous (TRAM) flap has become the well
      accepted method for breast reconstruction using autogenous tissue. The free TRAM
      flap allows one to perform this procedure with minimum complications because of
      the improved blood supply. The design of the flap, which is based on the deep
      inferior epigastric vessel, also avoids sacrifice to the abdominal wall. The flap
      is especially well suited for immediate reconstruction after mastectomy.

PMID- 9627775
TI  - The delayed TRAM flap.
AB  - As surgeons gain increased clinical experience with the transverse rectus
      abdominis myocutaneous (TRAM) flap, or autologous breast reconstruction,
      technical modifications aimed at improving flap reliability continue to evolve.
      These modifications have allowed the TRAM flap to be performed safely in a higher
      risk patient population. The delayed TRAM flap appears to have an augmented
      arterial supply and a lesser degree of venous congestion following division of
      the deep inferior epigastric vessels 2 weeks prior to reconstruction. Ischemia
      related complications have been reduced in high-risk patients with the use of the
      delayed TRAM.

PMID- 9627777
TI  - The deep inferior epigastric artery perforator flap.
AB  - This article describes the surgical technique of an autogenous breast
      reconstruction deep inferior epigastric artery (DIEA) perforator flap and
      presents clinical cases. Advantages of this technique in regard to donor site
      morbidity are discussed.

PMID- 9627778
TI  - Thoracodorsal vessels as a recipient site.
AB  - A variety of useful recipient vessel options exist for delayed breast
      reconstruction. The thoracodorsal vessels of the subscapular trunk, however,
      present the best option in immediate breast reconstruction, in particular for the
      transverse rectus abdominis myocutaneous (TRAM) flap, because of their consistent
      availability and reliability. One fundamental surgical advantage of the
      microvascular approach to breast reconstruction is the relative ease of obtaining
      consistently high-quality recipient vessels throughout the axilla and
      anterolateral chest wall to facilitate a predictably successful reconstructive
      outcome. This article discusses the process of selecting the best vessels and the
      techniques for their dissection.

PMID- 9627779
TI  - Internal mammary vessels as a recipient site.
AB  - In breast reconstruction with a free flap, the selection of suitable recipient
      vessels remains one of the most critical decisions for the surgeon. Most surgeons
      use one of the branches of the axillary vascular system, the thoracodorsal
      vessels. Because of a number of difficulties using this recipient site, the
      authors investigated the anatomy and availability of the internal mammary vessels
      for free flap breast reconstruction. This article describes the anatomic
      considerations, surgical technique, clinical experience, advantages, and
      limitations of using these vessels. In recent years, free autogenous tissue
      transfer for breast reconstruction has become increasingly common. The free
      transverse rectus abdominis myocutaneous (TRAM) flap and the more recently
      described deep inferior epigastric artery (DIEA) perforator flap are currently
      the methods of choice for postmastectomy breast reconstruction. For patients who
      cannot have a TRAM flap, free flaps from other donor sites (superior gluteal
      flap, inferior gluteal flap, Rubens flap, lateral transverse thigh flap) also
      have become important options.

PMID- 9627780
TI  - Shaping the autologous breast.
AB  - Autologous breast reconstruction has become increasingly popular in the past
      several years as more experience has been gained in the various techniques.
      Advantages to autologous reconstruction include improved shaping and symmetry,
      which also allow for a more natural reconstruction. The transverse rectus
      abdominis myocutaneous (TRAM) flap (free and pedicled) and latissimus flap are
      the predominant methods used although many newer donor sites have also been
      described. This article discusses techniques that allow the reconstructive
      surgeon to plan and execute the reconstruction of a natural breast reconstruction
      with autologous tissue.

PMID- 9627781
TI  - Abdominal wall complications. Prevention and treatment.

PMID- 9627782
TI  - Bilateral breast reconstruction.
AB  - For appropriate patients, who are aware of and accept the risks involved,
      contralateral prophylactic mastectomy and bilateral reconstruction can provide a
      good solution to an otherwise difficult problem. Bilateral reconstruction can
      produce exceptionally good aesthetic results and, because good symmetry is
      achieved in the initial surgery, it only costs about 5% more than unilateral
      reconstruction. This article discusses the techniques, advantages, and
      disadvantages of bilateral reconstruction.

PMID- 9627783
TI  - Autogenous latissimus breast reconstruction.
AB  - This article discusses the authors' experience with the reliable and easily
      shaped autogenous latissimus flap. The design and shaping of the flap are
      discussed as well as its use for both immediate and delayed reconstructions.

PMID- 9627784
TI  - Superior gluteal free flap breast reconstruction.
AB  - The authors substantial experience with the superior gluteal free flap for breast
      reconstruction indicates that this is a more difficult but important free flap
      for breast reconstruction. Compared with the standard transverse rectus abdominis
      myocutaneous (TRAM) free flap, it is a much less forgiving operation with many
      specific technical details. With careful attention to details on flap design,
      recipient vessel selection anastomsis, and flap insetting, the success rate and
      morbidity of the gluteal flap operation are highly acceptable. For patients
      unsuitable for the TRAM flap for autologous tissue reconstruction, this is a very
      valuable alternative. It can achieve some spectacular results in breast
      reconstruction in terms of volume, replacement, and projection--even in very thin
      patients.

PMID- 9627785
TI  - Inferior gluteal free flap breast reconstruction.
AB  - This article discusses the indications for and anatomy, technique, and results of
      breast reconstruction with the inferior gluteal free flap. The authors also
      present the results of their 25 inferior gluteal flap operations performed in the
      last decade.

PMID- 9627786
TI  - The Rubens flap. The deep circumflex iliac artery flap.
AB  - The Rubens free flap for breast reconstruction is another choice for autogenous
      tissue breast reconstruction. It uses the fatty area in the region generally
      described as the hip overlying or just above the iliac crest. It is based on the
      deep circumflex iliac artery and is indicated as a secondary choice in the
      presence of a previous abdominoplasty or transverse rectus abdominis myocutaneous
      (TRAM) flap breast reconstruction. Closure of the abdominal wall musculature
      along the iliac crest is the most exacting portion of this operation and is a key
      to its ultimate success.

PMID- 9627787
TI  - The superior gluteal artery perforator flap.
AB  - The gluteal region is an excellent donor site for autogenous breast
      reconstruction, particularly when the lower abdomen is not suitable. The superior
      gluteal perforator flap involves microsurgical transfer of skin and fat from the
      buttock without muscle sacrifice. Gluteal myocutaneous flaps have been described,
      but they have several problems, including a short vascular pedicle, exposure of
      the sciatic nerve, and recipient vessel size discrepancy needing vein grafts.

PMID- 9627788
TI  - Repair of partial mastectomy defects.
AB  - Deformities caused by partial mastectomy can often be helped by plastic surgical
      techniques. Immediate repair of partial mastectomy defects is especially useful
      when skin, as well as breast tissue, has been resected. Distant tissue can be
      used, but most partial mastectomy defects are best repaired with local flaps.
      Shifting the defect into the axilla, where it is less noticeable, is often
      helpful. Alternatively, the breast can be reshaped using techniques similar to
      those used in reduction mammaplasty. In that situation, reduction of the opposite
      breast often is indicated for symmetry.

PMID- 9627789
TI  - Choice of technique for reconstruction.
AB  - This article discusses the complex set of issues that go into choosing a
      technique for breast reconstruction. These factors include not only the technical
      aspects of breast restoration, but oncologic care, psychologic factors, and
      patient preference. The various flap options and indications for them are
      described.

PMID- 9627794
TI  - Adult X-linked immunodeficiency (XID) mice, IGM-/- single knockout and IGM-/- CD8
      /- double knockout mice do not clear polyomavirus infection.
AB  - The importance of antibodies for elimination of polyomavirus infection and the
      prevention of virus induced oncogenesis was studied, X-linked immunodeficiency
      (XID) mice, IgM-/- single knockout and IgMI-/- CD8-/- double knockout mice, all
      defective in antibody production, and normal control mice were infected with
      polyomavirus as adults. The mice were followed for presence of polyoma DNA with a
      polyoma specific polymerase chain reaction (PCR) over 6 weeks post infection
      (p.i.), a time point at which polyomavirus DNA is no longer detected in normal
      adult infected mice. As expected, virus DNA was not detected in normal mice 6
      weeks p.i. In both IgM-/- single knockout and IgM-/- CD8-/- double knockout mice
      a disseminated infection was still observed by 6 weeks p.i. and the latter group
      of mice succumbed around two months p.i. In XID mice, only one third of the mice
      were still positive for viral DNA 6 weeks p.i. No polyomavirus induced tumors
      were observed in any of the mice during the 2-4 month observation period.

PMID- 9627795
TI  - Leukemia inhibitory factor and steel factor regulate tie message stability in
      CD34+ cells from human umbilical cord blood.
AB  - The cell-surface receptor tyrosine kinase, Tie, is expressed in hematopoietic
      stem/progenitor cells. Leukemia Inhibitory Factor (LIF) and Steel Factor (SLF)
      have both been shown to up-regulate Tie gene expression in a population of CD34+
      cells derived from human umbilical cord blood (UCB) which is enriched for
      hematopoietic stem/progenitor cells. In the present study, we examined the
      possible mechanism of Tie gene up-regulation by LIF and SLF in CD34+ cells using
      semi-quantitative RT-PCR analysis. In the presence of Actinomycin D (Act D) alone
      for 24 hrs, Tie transcripts in CD34+ cells decreased. Tie mRNA was increased by
      an average of 2-4 fold and remained elevated level for 24 hours in CD34+ cells
      prestimulated with LIF or SLF followed by Act D, compared to that in CD34+ cells
      treated with Act D without prestimulation. After treatment of CD34+ cells with
      cycloheximide, Tie mRNA levels were decreased in the presence or absence of LIF
      or SLF at 24 hours. These findings suggest that LIF and SLF regulate Tie gene
      expression in UCB CD34+ cells at least in part through an increase in Tie message
      stability.

PMID- 9627796
TI  - Proteasomal RNase activity in human epidermis.
AB  - The proteasome is a cytoplasmic high-molecular-weight structure composed of
      several smaller protein and RNA subunits. It has been associated with non
      lysosomal pathways of intracellular degradation, expressing multicatalytic
      proteinase activities and specific RNase activity. By standard methods, we have
      isolated andpartially purified proteasomes from human epidermis. We obtained the
      expected multiple 24-32 kDa subunits by SDS-PAGE, and evidence of RNA.
      Proteasomes degraded casein, as well as chromogens for t-PA and trypsin but not
      for chymotrypsin, these proteolytic activities overlap, but do not coincide with
      those observed in other organs. We found that human epidermal 28 S and 18 S rRNAs
      were degraded, but yeast RNA was not. By means of zymography, we demonstrated,
      for the first time, that RNase activity persists after dissociation of the
      proteasome on the gel and that it co-localizes to the same range of molecular
      weight subunits as the proteinase activity.

PMID- 9627797
TI  - Inhibition of aberrant crypt foci by chemopreventive agents.
AB  - The colon carcinogenic process is believed to begin with both genetic and
      morphological alterations in a few individual crypts. These select crypts, called
      aberrant crypt foci (ACF), are widely agreed upon as precursors of colon cancer.
      The ACF assay involves testing potential chemopreventive agents by counting the
      number of ACF in a carcinogen-treated colon. This assay has the advantage of not
      only being less expensive and time-consuming than tumor-producing studies, but
      will also allow the elucidation of the colon carcinogenic process by letting the
      researcher explore the changes that occur at a pre-cancerous stage. The ACF assay
      has been used most frequently in rodent models. In the rodent colon, ACF are easy
      to distinguish due to their distinct morphological, histological, and biological
      characteristics. In addition, the ACF assay has been used to look at specific
      genetic alterations in the crypts such as K-ras, p53, and APC mutations. Our
      laboratory has consistently used the ACF assay to test many potential
      chemopreventive agents using rats induced by the colon carcinogen azoxymethane
      (AOM). Potential chemopreventive agents have been tested in both the initiation
      or the post-initiation period Research supports the notion that aberrant crypt
      foci represent a true neoplastic lesion for colon cancer. By studying these
      lesions both grossly and genetically it may be possible to learn more about the
      causes of colon carcinogenesis. In addition, by testing new compounds through the
      ACF assay, it is possible not only to discover potentially new chemopreventive
      compounds, but also to discover the mechanisms behind them. Because of this, the
      ACF assay is an invaluable method that will help reveal the process of colon
      carcinogenesis.

PMID- 9627799
TI  - The role of neutrophils as cytotoxic cells in lung metastasis: suppression of
      tumor cell metastasis by a biological response modifier (PSK).
AB  - We aimed to determine the role of neutrophils and the usefulness of a protein
      bound polysaccharide (PSK) in the suppression of tumor cell metastasis in the
      lung in vivo. Circulating neutrophils collected frm tumor-bearing animals (Line
      10 hepatocarcinoma) induced a marked decrease in the size and number of
      metastatic foci in the lung. Although pulmonary macrophages (PAMs), lymphocyte
      and eosinophil in bronchoalveolar lavage (BAL) fluid increased following tumor
      cell inoculation, in addition to these findings we found that PSK caused an
      increase in BAL neutrophil levels causing increased of target cell toxicity and a
      marked decrease in the size and the number of lung metastatic foci. Superoxide
      anion generation of blood neutrophils collected from PSK-treated animals with
      metastasis showed forward acceleration. The presence of neutrophil chemotactic
      factors was confirmed in the BAL fluid of PSK-treated animals with metastasis,
      but not leukotriene B4. The results suggest that modulation of the tumor cell
      microenvironment by activation of neutrophils may prove to be an additional
      modality in treatment strategy by combining PSK as a biological response modifier
      with conventional therapies for lung metastasis.

PMID- 9627798
TI  - Increased tissue oxygenation and enhanced radiation sensitivity of solid tumors
      in rodents following polyethylene glycol conjugated bovine hemoglobin
      administration.
AB  - BACKGROUND: Hypoxic tumors are frequently resistant to radiation therapy.
      Polyethylene glycol conjugated bovine hemoglobin (PEG-Hb) was tested for its
      ability to increase oxygen tension in the hypoxic rat osteogenic sarcoma UMR-106,
      murine Lewis lung carcinoma LL2 and rat gliosarcoma 9L. In addition, PEG-Hb was
      tested as an adjunct for radiotherapy in UMR-106 and human prostate carcinoma PC
      3 solid tumors. MATERIAL AND METHODS: Rodents bearing established subcutaneous
      tumors were intravenously administered PEG-Hb. Tumor surface tissue oxygen
      tension was measured by both OxySpot and OxyMap systems, which utilize the same
      phosphorescence quenching method. RESULTS: A time-dependent rise in oxygen
      tension was noted, and the maximum tissue oxygen tensions were observed two hours
      post PEG-Hb administration, and sustained for at least 2 hours. Following a
      single dose radiation of 4 Gray, osteogenic sarcoma tumors in the PEG-Hb treated
      group showed dramatic regression (complete remission occurred in 100% of the high
      dose PEG-Hb treated rats), as compared to control (Ringer's lactate) group tumors
      that showed continued aggressive growth. All PEG-Hb plus radiation treated
      animals bearing human prostate carcinoma (PC-3) showed significant tumor growth
      delay compared to both control (Ringer's lactate) and irradiation only treated
      animals. CONCLUSION: PEG-Hb increased tumor oxygen content and improved the
      effectiveness of radiotherapy in these rodent models.

PMID- 9627800
TI  - The detection of bile ducts in liver biopsies by cytokeratin 7.
AB  - In hematoxylin and eosin (H and E) stained sections from liver biopsies, the
      destruction of bile ducts in the portal triads is regarded as an important
      histologic parameter in the diagnosis of primary biliary cirrhosis (PBC). In
      contrast, the bile ducts are not destroyed by chronic inflammation in chronic
      active hepatitis (CAH). Nevertheless, the differential histologic diagnosis
      between PBC and virus or autoinmune-induced chronic active hepatitis (CAH), is
      very difficult in 15% of cases. That difficulty is mainly due to the
      impossibility of identifying bile ducts in the portal triads with marked
      lymphocytic infiltration. In this investigation we report that bile ducts may be
      specifically stained by anti-human cytokeratin 7 (CK7). Sections from 16 liver
      biopsies (PBC = 6, CAH = 6 and fatty liver (FL) = 4) were stained with H and E
      and CK7. The results in H and E stained sections indicated that the mean number
      of bile ducts found in PBC was was 0.56 (range 0-2), in CAH 0.67 (range 1-3), and
      in FL 0.56 (range 1-3). In parallel CK7 stained sections, the mean number of bile
      ducts in PBC was 5.33 (range 2-35), in CAH 3.44 (range 4-18), and in FL 1.39
      (range 2-6). The difference between H and E and CK7 stained sections was
      significant (p < 0.001) in all 3 groups. In the light of these preliminary
      results, it would appear that Cytokeratin 7 may be the stain of choice to detect
      bile ducts, an important parameter to histologically differentiate between PBC
      and CAH, as well as to classify PBC into its different stages.

PMID- 9627801
TI  - Effects of transferrin on the modulation of cytokine production on mouse spleen
      cells.
AB  - In order to investigate the the effects of transferrin(Tf) on the production of
      cytokines, mouse spleen cells were treated with various concentrations of apo-
      and holo-Tf, and then the production of IL-6, IFN gamma and the expression of
      mRNA for TNF alpha was determined. The distribution of Tf, macrophages and T
      cells in the mouse mammary glands was also examined. IL-6 and IFN gamma producing
      capabilities of the unstimulated spleen cells in the presence of apo and holo-Tf
      were increased in a dose dependent manner, while the cells stimulated with anti
      CD3 had no significant effects on production in thd presence of graded
      concentrations of Tf. The relative abundance of TNF alpha mRNA was significantly
      affected by the concentration of TF. During early involution almost all of the
      secretory epithelial cells and the secretion in the alveoli showed a very strong
      positive reaction to transferrin antibody, and macrophages and T cells were
      distributed in the lumen, alveolar epithelial layer and connective tissue area.
      These findings suggest that the upregulated patterns of these cytokines and
      distribution of immune cells may play a beneficial role in the augmentation of
      host's defense mechanisms during involution.

PMID- 9627802
TI  - Fetal cells in maternal blood: isolation by magnetic cell sorting and
      confirmation by immunophenotyping and FISH.
AB  - Fetal cells entering the maternal circulation during pregnancy constitute a
      potential source for safe and reliable non invasive prenatal diagnosis. However,
      selecting the appropriate fetal cell type and methods of enrichment are areas of
      paramount importance. Most investigators consider fetal nucleated red blood cells
      (NRBCs) to be the cell type of choice, since they are mononuclear, abundant in
      fetal blood, relatively well differentiated and have a limited life span. Twenty
      ml of peripheral blood samples were collected from 40 pregnant women in the 16th
      to 18th week of pregnancy. To enrich for NRBCs, found within an excess of
      maternal cells, negative magnetic cell sorting (MACS) was used. Leukocytes were
      depleted from maternal blood by treatment with anti CD45 monoclonal antibody, as
      this surface antigen is not expressed in NRBCs. NRBCs were detected in 35 of the
      40 maternal samples with May Grunwald-Giemsa staining. In 30 cases UCH gamma
      positive cells were identified after immunophenotyping with a monoclonal antibody
      directed against the gamma chain of fetal hemoglobin. The mean number of isolated
      NRBCs was 6 (range 1-15). In 5 cases we were able to successfully perform FISH on
      the immunophenotyped cells and determine correctly the fetal gender using X and Y
      chromosome specific probes.

PMID- 9627803
TI  - Early effect of cyclophosphamide on oncogene expression in vivo.
AB  - Cyclophosphamide (CP) is a widely used chemotherapeutic drug, with proven
      carcinogenic effects. Secondary tumours induced by CP are kidney tumours in
      humans and haemopoietic malignancies in rodents. Previous experiments have shown
      its effect on H-ras, c-myc and p53 gene expression in long term in vivo
      experiments. Our model was developed to analyse the events in the first 24 hours
      after the administration of CP in short term experiments. The expression of Ha 
      ras, c-myc and p53 was investigated in the target organs during and up to 24
      hours after the administration, at 0.25, 0.5, 1, 6, 12 and 24 h. Since the
      majority of CP-induced tumours are leukemias and lymphomas in the CBA/Ca mouse
      model, RNA was obtained from the thymus and the spleen. The results show that p53
      is strongly expressed in the thymus during the focused period. On the other hand,
      the samples were subjected to in situ hybridisation and compared with the results
      of in situ hybridisation of lung and liver samples. Comparing the results of
      total RNA and in situ hybridisation should prove useful if the total RNA signal
      is too weak or not detectable at all. The in situ hybridisation picture showed
      many positive cells without high expression of oncogenes. Further flow-cytometric
      studies are necessary to provide a full explanation of the mechanism of CP
      induced changes.

PMID- 9627804
TI  - Mouse trophoblastic cell lines: II--Relationship between invasive potential and
      proteases.
AB  - The specialized interaction between embryonic and maternal tissue is unique to
      mammalian development. This interaction begins with the invasion of the uterus by
      the first differentiated embryonic cells, the trophoblasts, and culminates in
      formation of the placenta. Because of their highly specialized behavior invasive
      cells must attach to the extracellular matrix proteins, secrete proteinases,
      capable of degrading matrix, and migrate through the degraded matrix; invasion is
      partially dependent on the proteinase activity of the cells. The objective,
      therefore, was to study a vitro system to examine the mechanism(s) of trophoblast
      cell invasion and its relationship to proteinases. Since little is known about
      the actual mechanism(s) involved. The mouse trophoblast cell lines established
      from placentas of different gestational ages were chosen to study their invasive
      properties in vitro. To begin to understand the biochemical basis of this
      behavior, the chromogenic assay and the substrate gel technique was used to
      analyze the cell associated and secreted plasminogen activators. All lines
      secrete and synthesize both urokinase-type (uPA) and tissue-type (tPA)
      plasminogen activators. The most invasive line SM9-2, derived from mid-gestation
      (day 9) placenta showed the highest enzymatic activity in the conditioned medium
      (CM), whereas in cell extract (CE) SM-10 line derived from late gestation
      placenta had the highest PAs activity. Four forms of secreted PAs in CM were of
      79, 72, 43 and 35 kDa molecular weights, whereas in CE only 79 kDa molecular
      weight form of PA was detected using substrate SDS-PAGE gels. Additional
      observations from cells cultured on Marrigel Invasion Chambers also showed
      secretion of PAs by noninvading and invading cells in a biphasic pattern suggest
      the involvement of these enzymes in the extracellular proteolysis. The expression
      of matrix metalloproteinase gelatinase B (MMP-9) and tissue inhibitor of
      metalloproteinase (TIMP-1) were examined by RT-PCR in all the lines, however MMP
      9 and TIMP-1 signals were strongly expressed in SM9-2 and SM-10 lines
      respectively. CM and CE were characterized by gelatin zymography, and the
      proteinases secreted by these cells in CM were confirmed to be metalloproteinases
      with approximate molecular masses between 52 to 92 kDa. Proteinases secreted by
      noninvading and invading cells cultured on Matrigel Invasion Chambers were not
      identical suggesting that specialized, temporally regulated metallopro-teinases
      are involved in trophoblast invasion. Trophoblast cell invasion in Matrigel
      Invasion Chambers was significantly inhibited in all the lines by using 1, 10
      phenanthroline, an inhibitor of metalloproteinases. The results indicated that
      mouse trophoblast cells have matrix--degrading capabilities through
      metalloproteinase activity. Similar metalloproteinase activity has been reported
      to be necessary for human trophoblast invasion, suggesting a similar mechanism of
      implantation. Trophoblast culture system described here should be useful in
      studying some of the early events in human placentation.

PMID- 9627805
TI  - Panax ginseng prevents apoptosis in hair follicles and accelerates recovery of
      hair medullary cells in irradiated mice.
AB  - We studied the effect of the water fraction of Panax ginseng, one of traditional
      oriental medicine herbs on apoptosis and the formation of medullary cell in the
      hair follicles of irradiated mice. The hair follicle or its differentiated
      product, the hair, which represents a linear historical record of follicular
      proliferative activity, could provide a biological indicator of the effect of
      radioprotective drugs. Adult N:GP(s) mice with hair follicles synchronously in
      the middle of the hair growth cycle received whole-body doses of gamma-radiation.
      The hair follicles were analysed either 12 hours after irradiation with 2 Gy in
      the experiment on the apoptosis, or 3 days after irradiation with 3 Gy in the
      experiment on the forming medulla. The number of medullary cells per unit length
      (100 microns) were measured by H and E staining. Apoptosis was detected by a
      nonisotopic in situ DNA end-labeling (ISEL) technique and H and E stain applied
      to the serial histologic sections. Ginseng administration before irradiation
      resulted in a suppression of apoptosis, as shown by a reduced number of cells
      stained with ISEL for fragmented DNA, both i.p. (0.3 mg/head, p < 0.05) and p.o.
      (2 mg/ml of drinking water, p < 0.05) treatment. In addition, ginseng treatment
      was associated with an increase in the number of medullary cell per unit length
      as compared with the vehicle treated mice (p < 0.001, i.p.; p < 0.05, p.o.).
      These results indicate that the water fraction of ginseng can exert a potent
      effect on the recovery of the hair follicles by its combined effects on
      proliferation and apoptosis of the cells in the hair follicle.

PMID- 9627806
TI  - Antitumor activity of creatine analogs produced by alterations in pancreatic
      hormones and glucose metabolism.
AB  - When rats bearing the 13,762 mammary carcinoma were treated with intravenously
      administered creatine analogs, cyclocreatine, beta-guanidinopropionic acid or
      creatine phosphate on days 4 through 8 and 14 through 18 post tumor implantation,
      the tumor growth delay produced varied with whether the animals were drinking
      water or sugar water over the course of the study. The tumor growth delays
      increased when the animals drank sugar water from 9.3, 1.6 and 7.6 days for
      cyclocreatine, beta-guanidinopropionic acid and creatine phosphate, respectively,
      to 15.0, 6.3 and 12.6 days. Blood glucose was decreased over the course of the
      creatine analog treatment regimen and the skeletal muscle transport protein GLUT
      4 increased 1.5 to 2-fold with the creatine analog treatments. Plasma insulin was
      profoundly decreased to 20-25% of normal by the creatine analog treatment while
      plasma glucagon levels were increased. Plasma somatostatin increased 3- to 4-fold
      during the administration of the creatine analogs. These results implicate
      alterations in pancreatic hormone balance in the antitumor activity of these
      creatine analogs.

PMID- 9627807
TI  - Cell-water transfer and stability of biological structures (resonance of
      biological structures).
AB  - A model is proposed according to which life is the totality of resonant
      thermodynamically open systems. The Earth's physical fields are the necessary
      condition of these systems existence and their dynamic stability. The size of the
      cell is a function of the magnetic field intensity according to the proposed
      equation. Thermodynamic equations are also proposed for the computation of the
      optimal oxidation stage and membrane potential, and for the water dielectric
      permeability. All equations result in values which correspond to experimental
      data without fitting coefficients. The proposed theory explains the structure of
      the biological system as result of the dynamic stability and least action
      principle. This theory also includes the explanation of the influence of Earth
      magnetic field and analysis of associated water properties.

PMID- 9627808
TI  - Carcinogenesis studies with the lyophilized mushroom Agaricus bisporus in mice.
AB  - Continuous administration of 10, 5, and 2.5% lyophilized Agaricus bisporus (AB)
      mushroom in the diet of six-week-old, randomly bred Swiss mice for life induced
      tumors in the lungs, forestomach, glandular stomach, and ovaries in certain
      groups. Some of the tumor incidences were found to be statistically significant,
      although no dose-response relationship was established. Histopathologically, the
      neoplasms were classified as adenomas and adenocarcinomas of lungs, glandular
      stomach, and ovaries and squamous cell papillomas and carcinomas of the
      forestomach. AB given in both raw and baked forms induced tumors in the same
      species in earlier experiments. Since this fungus is consumed in lyophilized form
      to a certain degree in the United States, the results may carry practical
      significance.

PMID- 9627809
TI  - Influence of the flow rate during flushing on porcine multivisceral preservation.
AB  - The effect of flushing flow rate during multiple organ procurement (MOP) on
      viability of the liver, pancreas, and intestine were investigated in porcine
      multivisceral transplantation. Splanchnic organs were flushed in situ with 50
      ml/kg of 4 degrees C UW solution via the aorta using a pump at a flow rate of 10,
      30, or 50 ml/kg/min. After storage and transplantation, we assessed the clearance
      of hyaluronic acid (CHA) for hepatic endothelial cells function, liver enzymes,
      amylase, and histology. Two-day survival was 17% in the 10 ml/kg/min group and
      67% in other groups. The former group had inadequate flushing out of the hepatic
      and intestinal grafts, resulting in aggravation of CHA and intestinal tissue
      injury. At the flow rate of 30 ml/kg/min, the viability and integrity of all
      organs were well maintained. We conclude that the optimal flushing flow rate
      would differ for each organ, therefore the common flow rate acceptable for any of
      the individual grafts should be applied in MOP.

PMID- 9627810
TI  - Thyroxine-induced production of superoxide anion by human alveolar neutrophils
      and macrophages: a possible mechanism for the exacerbation of bronchial asthma
      with the development of hyperthyroidism.
AB  - Bronchial asthma worsens after the development of hyperthyroidism. However, the
      biochemical mechanism of this phenomenon, which is induced by thyroxine (T4),
      remains obscure. In the present study, we showed that T4 directly stimulates
      production of superoxide anion by alveolar neutrophils and macrophages. These
      cells, when sensitized with a patient's serum and then treated with both the
      patient's specific allergen and T4, produced higher amounts of superoxide anion
      than did sensitized cells treated with the specific allergen or T4 alone. Our
      data suggest that T4 enhances production of reactive oxygen species by alveolar
      neutrophils and macrophages, which might play an important role in the
      exacerbation of bronchial asthma with the development of hyperthyroidism.

PMID- 9627811
TI  - Small bowel rejection in isolated small bowel transplantation and in
      multivisceral transplantation: a comparative study in a large animal model.
AB  - The proposition that a combined graft including the liver protects other organ
      allografts from the same donor is well known. However, it is not evident in the
      clinical results. The present experiments were undertaken to compare acute small
      bowel rejection in isolated small bowel transplantation with multivisceral
      transplantation. Using 36 outbred, male Large-White pigs, isolated small bowel
      transplantation (SBTX: n = 9) and abdominal multivisceral transplantation (MVTX:
      n = 9) were performed without immunosuppression. The survival rate and blood
      serum samples were monitored postoperatively. In order to compare acute small
      bowel rejection, sequential biopsy specimens from Thiry-Vella loops were also
      monitored daily beginning on me 3rd day after transplantation. The specimens were
      scored from 0 to 3 according to the severity of the rejection. The survival rate
      was not significantly different. However, significant differences were noted in
      the cause of the death and in the pathologic changes of the small bowel. In
      contrast to SBTX, the small bowel rejection of MVTX was significantly delayed and
      less severe. The rejection score of MVTX was significantly better than SBTX from
      5 postoperative days (POD) to 1 lPOD (P < 0.05). The present study demonstrated
      mat acute small bowel rejection of MVTX graft including the liver was delayed and
      less severe than that of SBTX in an outbred large animal model.

PMID- 9627812
TI  - Primary care physicians' screening of adolescent patients: a survey of California
      physicians.
AB  - PURPOSE: To determine how often primary care physicians screen adolescents for
      important risk factors and to determine how rates of screening vary by
      physicians' specialty and practice setting, patients' age, and type of risk
      factor. METHODS: A stratified random sample of 343 California physicians who are
      Board certified in pediatrics, family practice, or internal medicine, and
      physicians in these specialties who specialized in adolescent medicine were
      surveyed about their screening practices using a mailed questionnaire. Subjects
      were asked the percentage of routine comprehensive physical examination during
      which they personally queried or screened each age group of adolescents (11-14
      years old and 15-18 years old) for each of the following risk factors: high blood
      pressure, alcohol use, cigarette use, sexual activity, and drug use. RESULTS: The
      frequency with which primary care physicians reported actually screening younger
      and older adolescents for the various risks were approximately: 93% and 96% for
      high blood pressure, 70% and 84% for alcohol use, 74% and 82% for drug use, 67%
      and 83% for sexual activity, and 76% and 86% for smoking, respectively. For all
      risk factors, providers screened older adolescents more frequently than younger
      adolescents (p < 0.01). Finally, screening rates varied by specialty (p < 0.01)
      but not by practice setting. CONCLUSIONS: This study found that California
      physicians frequently screen adolescents for a variety of risk factors. However,
      the reported rates may not be consistent with published guidelines. Interventions
      may need to be developed which focus on improving primary care physicians'
      adolescent-specific screening practices.

PMID- 9627813
TI  - Knowledge of health insurance coverage by adolescents and young adults attending
      a hospital-based clinic.
AB  - PURPOSE: To describe adolescents' and young adults' knowledge about their health
      insurance, and to identify factors associated with correct knowledge of health
      insurance in this population. METHODS: Data were analyzed from a confidential
      questionnaire administered to 830 patients at a hospital-based adolescent
      medicine clinic. The questionnaire contained items pertaining to insurance type,
      demographics, health status, and health-risk behaviors. Actual health insurance
      data and information regarding utilization of health services were obtained from
      the hospital billing data-base. Predictors of health insurance knowledge were
      determined through bivariate analyses followed by stepwise logistic regression.
      RESULTS: A total of 50.7% of respondents correctly identified their type of
      health insurance. Those who correctly identified their insurance had a higher
      mean age. Only 48.5% of participants who were 11-18 years old could identify
      their insurance type, versus 53.1% of 19-21-year-olds and 64.7% of 22-24-year
      olds (p = 0.02). Sixty-five percent of Medicaid patients and 76.3% of hospital
      free care patients knew how their medical bills were paid, versus 17.9% of self
      pay patients and 47.3% of patients with private insurance (p < 0.01). Greater
      utilization of health services was associated with increased rates of insurance
      knowledge among 19-24-year-olds on bivariate analysis; however, this factor was
      not significant when controlling for other factors. Regression analysis revealed
      that older age and insurance type other than self-payment were independent
      predictors of health insurance knowledge in adolescents (11-18 years old), while
      female gender and insurance type other than self-payment were independent
      predictors of insurance knowledge in young adults (19-24 years old). CONCLUSIONS:
      Approximately half of adolescents and young adults do not know how their medical
      bills are paid. Validation of self-reported insurance data is, therefore,
      critical both in clinical practice and health services research.

PMID- 9627814
TI  - Adolescent satisfaction with postpartum contraception and body weight concerns.
AB  - PURPOSE: To explore factors that could be related to adolescents' satisfaction
      with postpartum contraceptives. METHODS: Three focus groups were conducted with a
      total of 22 adolescent mothers. The groups covered four content areas: feelings
      about birth control since becoming a mother, decision making about contraceptive
      use, factors that would influence contraceptive discontinuation, and the
      perceived side effects of the current contraceptive. Audiotapes from the groups
      were analyzed to identify major themes. RESULTS: Nineteen subjects received Depo
      Provera when they were discharged after delivery and the majority reported that
      menstrual irregularities and weight gain were side effects. Two body weight
      related themes were dominant: dissatisfaction with heavier than desired body
      weights and resignation about not returning to prepregnancy weights. CONCLUSIONS:
      Depo-Provera may be an effective contraceptive for adolescent mothers who are
      generally at high risk for rapid repeat pregnancy. This qualitative study
      suggests that contraceptive continuation may be enhanced with specific
      counselling to manage body weight concerns.

PMID- 9627815
TI  - Facing facts. Sexual health for American adolescents.

PMID- 9627816
TI  - Health risk behaviors of adolescent participants in organized sports.
AB  - PURPOSE: To assess differences in health-related behaviors between athletes and
      nonathletes. METHODS: In Grades 9-12 in seven high schools during the 1991-1992
      academic year, 7179 (82%) students were asked to complete a survey with six
      categories of health-related behaviors associated with adolescent morbidity and
      mortality. Of the 6849 students who completed the survey, 4036 (56%) were
      classified as athletes. Analyses of differences were controlled for age, race,
      and gender. RESULTS: Athletes and nonathletes differed in specific health-risk
      behaviors. Nonathletes were more likely than athletes ever to have smoked
      cigarettes (15% vs. 10%) or used marijuana (24% vs. 23%), and fewer ate breakfast
      daily (34% vs. 45%), never added salt to food (18% vs. 22%), consumed calcium
      (56% vs. 64%), or consumed fruit or vegetables (40% vs. 47%) daily. More
      nonathletes reported frequent feelings of hopelessness (15% vs. 10%) and rarely
      or never using seatbelts (24% vs. 20%), but more athletes reported exceeding the
      speed limit by 10 mph (39% vs. 35%) and riding bicycles (40% vs. 28%) and/or
      motorcycles (13% vs. 8%) without helmets. These differences were statistically
      significant. CONCLUSIONS: Because of their behaviors, adolescent athletes put
      themselves at significant risk for accidental injuries. However, athletes appear
      less likely to smoke cigarettes or marijuana, more likely to engage in healthy
      dietary behaviors, and less likely to feel bored or hopeless.

PMID- 9627817
TI  - Parental influences predict adolescent smoking in the United States, 1989-1993.
AB  - PURPOSE: To examine parental influences on two transitions in the adolescent
      smoking uptake process: from never having smoked to experimentation and from
      experimentation to established smoking. METHODS: Using data from the longitudinal
      Teenage Attitudes and Practices Survey of 1989-1993, we related perceived
      parental concern about their adolescents' future smoking, parental smoking
      status, problem-solving communication between parent and adolescent,
      demographics, and other factors at baseline to experimentation by follow-up among
      those who had never puffed on a cigarette (n = 4149). We also related these
      factors at baseline to reaching a lifetime level of smoking of at least 100
      cigarettes by follow up among those who had experimented but smoked < 100
      cigarettes (n = 2684) in univariate and multivariate analyses. RESULTS: Among
      never-smokers, baseline susceptibility to smoking and having male best friends
      who smoke predicted experimentation in the next 4 years. Among experimenters,
      susceptibility to smoking, having male or female best friends who smoked, and
      lack of parental concern about future smoking distinguished those who progressed
      to established smoking by follow-up. Furthermore, communicating with parents
      first about serious problems was protective against progression from
      experimentation to established smoking. CONCLUSION: Interventions aimed at
      reducing adolescent smoking should encourage cessation for parents who smoke and
      help parents communicate strong anti-smoking norms to children and adolescents
      and maintain strong lines of communication with them.

PMID- 9627818
TI  - Determinants of adolescents' satisfaction with health care providers and
      intentions to keep follow-up appointments.
AB  - OBJECTIVE: To better understand the determinants of adolescents' satisfaction
      with their health care providers and to examine the relationship among
      satisfaction, intention to return for follow-up, and appointment-keeping
      behavior. METHODS: One hundred and twenty-four adolescent patients attending a
      university-based general adolescent medicine clinic were surveyed prior to the
      visit about their attitudes regarding provider behavior. After the visit,
      subjects completed a questionnaire on provider behavior during the visit,
      satisfaction with the visit, and intention to keep their follow-up appointment.
      RESULTS: Multivariate regression analysis revealed that pre-visit attitudes about
      providers' style of behavior predicted satisfaction (beta = 0.252; p < 0.01).
      After controlling for pre-visit attitudes, perceptions about providers' style of
      behavior proved to be a strong predictor of visit satisfaction (beta = 0.512; p <
      0.01). Visit satisfaction was associated with intention to keep scheduled follow
      up appointments (r = 0.327; p < 0.01). However, subjects with greater intention
      to return were not more likely to keep their follow-up appointments. CONCLUSION:
      Provider behavior is an important determinant of adolescents' satisfaction with
      their health care.

PMID- 9627819
TI  - The prevalence of facial acne in Peruvian adolescents and its relation to their
      ethnicity.
AB  - PURPOSE: This article describes the prevalence of facial acne vulgaris in
      adolescents of Arequipa, Peru, in relation to ethnic characteristics. METHODS:
      This was a cross-sectional study of 2214 healthy adolescents, 55.83% male and
      44.17% female, 12-18 years old. Based on visual inspection, the severity of acne
      was classified into four grades. The adolescents studied were divided into three
      ethnic groups: whites, Mestizos, and Indians. RESULTS: Less than half of the
      adolescents (41.69%) had acne: 33.74% grade 1, 5.19% grade 2, 2.12% grade 3, and
      0.63% grade 4. The prevalence of acne varied from 16.33% at 12 years to 71.23% at
      17 years. At age 12 and 13 years, the prevalence of acne was higher in females,
      with the trend reversing over age 14 years. The overall prevalence of acne was
      significantly less in Indians (27.97%) than in Mestizos (43.08%) or whites
      (44.47%). More acne was found in postmenarche (39.90%) than in premenarche
      (20.99%). This trend was also true for the severity of acne. CONCLUSIONS: The
      prevalence of acne in the adolescents of Arequipa is significantly less than in
      Caucasians. Peruvian Indians have significantly less acne than Peruvian whites or
      Mestizos. It seems that ethnicity is an important predictor of not only the
      prevalence, but also the severity of juvenile acne vulgaris in this sample.

PMID- 9627820
TI  - Pulmonary function and dyspnea/suffocation theory of panic.
AB  - This article presents a brief discussion of pulmonary function and panic attacks
      in the context of respiratory psychophysiology. Ley's (Behaviour Research and
      Therapy, 27, 549-554, 1989) earlier dyspnea/suffocation theory of panic is
      contrasted with Klein's (Archives of General Psychiatry, 50, 306-316, 1993) later
      false suffocation alarm theory. The distinction between "dyspnea" (the sensation
      of difficulty in breathing) and "suffocation" (a condition that sometimes gives
      rise to dyspnea) is emphasized. The brief discussion is followed by a critical
      comparison of two recent studies on pulmonary function and panic. Asmundson and
      Stein (Journal of Anxiety Disorders, 8, 63-69, 1994) reported an association
      between forced expiratory flow rate (a measure of pulmonary function) in panic
      disorder patients and the severity of panic-related symptoms. They interpreted
      their findings as support for the dyspnea/suffocation theory of panic since
      severity of dyspnea is a consequence of pulmonary function. Spinhoven et al.
      (Behaviour Research and Therapy, 33, 457-460, 1995) failed to replicate the
      findings of Asmundson and Stein. The present paper provides a critical analysis
      of the study by Spinhoven et al. and concludes that the failed attempt to
      replicate may have been a consequence of a flawed methodology (the subjects of
      the two studies are not comparable on a crucial pulmonary test) and a statistical
      anomaly (disproportionately small differences between means that exceed
      predictions based on sampling error). A recommendation is made that future
      attempts to replicate should pay special care to avoid the possibility of
      experimenter-demand effects.

PMID- 9627821
TI  - Impact of a mandatory behavioral consultation on seclusion/restraint utilization
      in a psychiatric hospital.
AB  - Despite demonstrations of the utility and cost effectiveness of behavioral
      methods for improving care for people with psychiatric impairments, they are
      seldom employed effectively in inpatient settings. This study evaluated the
      impact of an administrative procedure to effect a behavioral consultation for
      cases of high seclusion/restraint utilization. Seclusion/restraint use for the 53
      cases was reviewed for a time period of 6 months before and 6 months after
      development of a behavioral treatment plan resulting from this procedure. The
      data revealed a 62% reduction in seclusion/restraint use after development of an
      approved plan. There was also a reversal in serial trend from increasing use
      during the months prior to plan development to decreasing use during months after
      plan development. The procedure is described and implications of the results for
      clinicians and administrators of psychiatric inpatient programs are discussed.

PMID- 9627822
TI  - Effectiveness of anxiety management training in the treatment of posttraumatic
      stress disorder: a preliminary report.
AB  - This preliminary study investigated the effectiveness of anxiety management
      training (AMT), a coping skills treatment similar to systematic desensitization,
      in comparison to implosive therapy (IT), an exposure-based treatment, for
      treating six Vietnam combat veterans with posttraumatic stress disorder (PTSD).
      The Clinician Administered PTSD Interview Scale (CAPS; Blake et al. (1988), The
      Behaviour Therapist, 18, 187-188) and a self-monitoring measure (Weathers et al.,
      1991) were used as dependent measures. A single-subject, multiple-baseline,
      crossover design (ABC/ACB) was employed. A new statistic for such designs (Mueser
      et al. (1991), Behaviour Modification, 15, 134-155), based on classical test
      theory, was used to assess treatment effects on intrusive war memories and
      avoidance of stimuli reminiscent of war. Within-subject results indicated that
      AMT and IT were similarly effective in reducing the frequency and intensity of
      intrusions and avoidance. This preliminary report therefore suggests that it may
      be productive to investigate multidimensional approaches (combining coping
      skills, exposure-based, and other approaches) to the treatment of combat-related
      PTSD as Foa et al. (1991), Journal of Consulting and Clinical Psychology, 59, 715
      723 and Nishith et al. (1995), Behaviour Therapy, 26, 319-335 have for rape
      related PTSD.

PMID- 9627823
TI  - Overview of the treatment of rumination disorder for adults in a residential
      setting.
AB  - Rumination, or the chewing and re-swallowing of regurgitated stomach contents,
      can be found in up to 10% of institutionalized individuals with severe or
      profound mental retardation. Serious physical consequences, including death, can
      result from the disorder. Unfortunately, rumination can be subtle and difficult
      to observe and often continues untreated. Additionally, the research literature
      has provided divergent results without clear treatment guidance for clinicians.
      We present an overview of the history of rumination, a review of the literature
      on its etiology and treatment, and recommendations for future research.

PMID- 9627824
TI  - Evaluating Spanish protocols for teaching bonding, home safety, and health care
      skills to a mother reported for child abuse.
AB  - A Spanish-speaking mother reported for child abuse of her 6-yr-old son and
      referred by child protective services received Spanish training protocols in
      their home provided by Project SafeCare. Treatment consisted of (1) child health
      care training, (2) planned activities training (PAT), and (3) home safety
      training. Following training, the mother met criterion in all training
      components. Although PAT was conducted with the mother and her youngest child
      only, the mother reported decreases in negative interactions between the oldest
      (untreated) child and his parents. Follow-up observations indicated that
      treatment gains were maintained. The mother rated the content and outcome of the
      training favorably on a social validation questionnaire.

PMID- 9627825
TI  - Non-aversive reduction of cigarette smoking in two adult men in a residential
      setting.
AB  - Two middle-aged men with mental retardation, addicted to smoking cigarettes,
      operated spinners that determined the probability with which they could obtain
      cigarettes and other items. Absence of several maladaptive behaviors permitted
      the operation of the spinners hourly (i.e., DRO 60 min), 16 h per day, 7 days per
      week. The actual frequencies of obtaining cigarettes followed the theoretical
      probabilities of obtaining cigarettes in all phases of the study. Presumed
      smoking frequencies were reduced by about 50% with associated medical benefits.
      Low frequencies of maladaptive behaviors were maintained throughout.

PMID- 9627826
TI  - The relationship between food refusal and self-injurious behavior: a case study.
AB  - Food refusal and self-injurious behavior often co-occur in children with
      developmental disabilities and mental retardation. The subject of the case study
      was a 3-yr-old boy with food refusal, self-injurious behavior and developmental
      delay. Using an alternating treatment design, positive reinforcement for
      acceptance combined with either nonremoval of the spoon or guidance for refusal
      increased food acceptance and resulted in a decrease in self-injurious behavior
      despite not being targeted. Although the contingencies for acceptance, refusal
      and self-injurious behavior remained constant, self-injurious behavior increased
      with an increase in grams consumed. A combined treatment of positive
      reinforcement for acceptance, guidance for refusal, position change and
      gastrojejunal feedings resulted in a decrease in self-injurious behavior and an
      increase in grams consumed.

PMID- 9627827
TI  - The use of exposure with response prevention in a male anorexic.
AB  - The present case study describes the use of exposure with response prevention
      (ERP) in a 24-yr-old male with anorexia nervosa. In this case, ERP offered an
      opportunity to address problematic cognitions and decrease the anxiety associated
      with consumption of high fat/high calorie foods. By the end of 34 treatment
      sessions, the client's distress decreased while eating high-fat/high-calorie
      foods and he integrated a greater variety of foods in his diet. Implication for
      conceptualizing anorexia nervosa within an anxiety reduction/avoidance cycle is
      discussed with reference to the recent literature.

PMID- 9627828
TI  - Functional assessment and treatment of sleeping problems with developmentally
      disabled children: six case studies.
AB  - Sleeping problems are common among developmentally disabled children of young age
      and they may have adverse effects on the well-being of both child and parents. In
      the present study, results from functional assessment with four children
      suggested that sleeping problems were reinforced by parental attention whilst an
      undiagnosed seizure disorder was associated with nighttime crying with one child.
      Conditioned anxiety resulted in problems in settling to sleep with a sixth child.
      Behavioral (i.e., extinction, desensitization) and pharmacological (i.e.,
      anticonvulsant) treatment resulted in a substantial reduction in sleeping
      problems with all children. Follow-up data indicate that effects were maintained.

PMID- 9627829
TI  - Dr. Bruce R. McCord.

PMID- 9627830
TI  - Capillary electrophoresis in court: the landmark decision of the People of
      Tennessee versus Ware.
AB  - Capillary electrophoresis is a versatile and emerging technique. In the fields of
      law and science, history has been made with the admissibility of CE as a method
      to evaluate evidence. The extremely low sample requirements, high separation
      efficiencies, and excellent resolution allow for quantitative techniques from
      extracted and amplified mitochondrial DNA (mtDNA), which was presented as
      evidence from hair shafts in the case of The People of Tennessee versus Paul Ware
      (Tennessee v. Ware). This paper discusses the history of the admissibility of
      scientific evidence. In 1993, the United States Supreme Court Justices rewrote
      the rules for admission of scientific evidence under the Federal Rules of
      Evidence (FRE) in Daubert v. Merrell Dow Pharmaceuticals, Inc. (Daubert) (509
      U.S. 597). After rejecting the longstanding requirements under Frye v. United
      States (Frye), 293 F.1013 (1923), which focused on the conclusions obtained
      rather than the methodologies employed, Daubert went further in establishing a
      liberal policy in the FRE favoring the District Court judges to act as
      gatekeepers, thus admitting well-grounded scientific evidence. Later this year,
      the Supreme Court will once again review the issue of how the decisions reached
      in trial courts should be treated by reviewing courts. CE has demonstrated its
      ability to meet the requisite scientific standards in the court system. The CE
      evidence presented in Ware led to a felony conviction.

PMID- 9627832
TI  - Phosphodiesterase susceptibility of modified oligonucleotides studied in an
      integrated capillary electrophoresis system.
AB  - A capillary electrophoresis system that integrated an enzymatic reaction and
      capillary polymer sieving electrophoresis was used to check the enzymatic
      stability of oligonucleotides. Phosphodiesterase I was employed to assess the
      susceptibility to 3'-exonucleolytic breakdown of some unmodified and modified
      oligonucleotides. Before degradation, the purity of the synthetic
      oligodeoxynucleotides was checked by capillary electrophoresis with a replaceable
      hydroxyethyl cellulose polymer solution. Enzymatic breakdown was achieved inside
      the capillary by merging substrate and enzyme zones based on their difference in
      electrophoretic mobility. After reaction, oligonucleotide fragments were swept to
      the detector, where they were individually detected and the remaining substrate
      was quantified. The results from the in-capillary degradation were compared to an
      off-line incubation and separation.

PMID- 9627831
TI  - Use of capillary electrophoresis in the characterization of sulfonated
      metallophthalocyanines: a comparative evaluation of purification procedures
      following synthesis by the condensation method.
AB  - Capillary electrophoresis has been presented as a resourceful technique for
      monitoring the purity of synthetic metallophthalocyanines and evaluating
      comparatively purification procedures. In this study, the tetrasulfonated
      cobalt(II) phthalocyanine was synthesized by the condensation method and
      submitted to several purification procedures such as continuous Soxhlet
      extraction with ethanol and dioxane, percolation through a gel-filled
      chromatographic column, and salting-out precipitation in acid medium followed by
      washing with alkaline solution. The efficiency of each procedure, or combined
      procedures, was then evaluated by capillary electrophoresis in citrate buffer
      solution under constant voltage conditions and direct UV-VIS detection at 630 nm
      and 260 nm. The inorganic anion and cation composition of the purified fractions
      was also investigated by indirect UV analysis in chromate/cetyltrimethylammonium
      bromide (CTAB) and imidazole/hydroxyisobutyric acid (HIBA) electrolyte systems,
      at 254 nm and 214 nm, respectively. The electropherograms obtained at 630 nm
      showed a high-intensity peak surrounded by satellite peaks of small intensity
      with migration time of approximately 5-6 min. This profile is indicative of the
      formation of positional isomers under the synthesis conditions. The
      electropherograms obtained at 260 nm were useful to monitor contaminants, such as
      reaction by-products or unreacted starting materials. The salting-out
      precipitation of the crude product led to a good-quality product with 80% purity
      (elemental analysis based on nitrogen content), which is comparable to the purity
      of commercially available tetrasulfonated derivatives. Both UV and infrared (IR)
      spectra of the purified product resemble that of standards. The capillary
      electrophoresis ion analysis of the treated product revealed the presence of
      sodium carbonate as the major contaminant. The combined treatment of salting-out
      precipitation followed by percolation in a Sephadex column (Pharmacia, Sao Paulo,
      Brazil) was successful for the removal of carbonate ion. However, the percolation
      procedure seemed to cause minor demetallation of the macrocycle ring, as
      confirmed by the presence of free cobalt(II) in the electropherogram of the
      column eluted fraction.

PMID- 9627833
TI  - Correlation of the intercept and slope of the retention equation ln k' = ln k'w -
      SC in MECC with the solvatochromic parameters of solutes.
AB  - The intercept (ln k'w) and slope (S) of the retention equation in k' = ln k'w -
      SC in micellar electrokinetic capillary chromatography (MECC) have been studied
      through linear solvation energy relationships (LSER). It has been observed that
      the ln k'w is dependent on the properties of micelle and solute but independent
      of the properties of organic modifier, while the slope (S) is related to the
      organic modifier and the solute. The LSER results show that the ln k'w of solute
      is primarily determined by its molecular size and hydrogen bond acceptor (HBA)
      basicity, whereas the S of solute is primarily determined by its properties in
      terms of the type of organic modifier, of which molecular size is the most
      important factor. Additionally, the LSER results show that the interactions of
      micelle-water and water-organic modifier are also important factors for the
      retention of solute.

PMID- 9627834
TI  - Chiral separations by capillary electrophoresis in process chemistry.
AB  - The utility of capillary electrophoresis in process chemistry to
      evaluate/optimize a synthetic organic process like classical resolution is
      demonstrated. Simultaneous monitoring of degradation products and optical purity
      is shown.

PMID- 9627835
TI  - Analysis of the transformation of nitroaromatic compounds in wastewater by
      bacteria using micellar electrokinetic capillary chromatography.
AB  - A rapid micellar electrokinetic capillary chromatographic method is described for
      the analysis of nitroaromatic and nitramine explosives using sodium dodecyl
      sulfate-borate buffer with application to analyze specifically the biodegradation
      products of trinitrotoluene. The method is fast, in expensive, offers better
      resolution, and saves on the consumption of organic solvents used in a comparable
      reversed-phase HPLC method.

PMID- 9627836
TI  - Capillary electrophoresis for meat species differentiation.
AB  - A sodium dodecyl sulfate (SDS) polymer-filled capillary gel electrophoresis (CE
      SDS) method was developed and optimized for the determination of meat proteins
      for species differentiation. Sarcoplasmic proteins were extracted with cold
      bidistilled deionized water and myofibrillar proteins with 0.6 M NaCl/0.01 M
      phosphate buffer with 0.5% polyphosphates at pH 6 from raw beef, turkey, and pork
      muscles. Samples were prepared for CE-SDS and the experimental conditions,
      including sample size, applied voltage, reducing agent, and its concentration,
      were obtained after a univariate optimization process. Separation of the
      sarcoplasmic and myofibrillar meat proteins was achieved with the optimized
      conditions of the CE-SDS method developed. The coefficient of variation was less
      than 1.15% in migration time for all peaks and less than 8.5% in area percentage.
      The CE-SDS sarcoplasmic protein profiles that resulted were specific for each
      species both qualitatively and quantitatively and could be employed for
      differentiation and identification purposes. This CE-SDS method can be used by
      regulatory agencies for rapid analysis of meat proteins to identify meat species.
      Automation, fast separation, and on-line data analysis are major advantages of
      this technique.

PMID- 9627837
TI  - Sole disorders in conventionally managed and organic dairy herds using different
      housing systems.
AB  - Records of claw trimmings were analysed in seven organic and six conventional
      Danish herds (a total of 974 cows). The housing systems represented were tie
      stall systems, loose housing system with slatted floor (one organic herd), and
      deep litter systems (deep straw bedding). Occurrence of sole disorders was
      analysed separately for cows in first lactation and for cows in later lactations.
      Three different responses (acute haemorrhage, sole ulcer in one leg and sole
      ulcer in two or more legs) were analysed using three binomial logistic regression
      analyses for each group. Herd analysed as a fixed effect was a strong risk factor
      for all kinds of sole ulcer. Lactation stage was a risk factor for acute
      haemorrhage in both groups of cows, and for sole ulcer in first parity cows. In
      general, there was a strong positive association between the period 61-120 d post
      partum and the presence of sole disorders. Breed was associated with acute
      haemorrhage in cows in second and later parities, and sole ulcer in one leg only
      in first parity cows in an interaction with lactation stage in both conditions.
      Danish Friesian cows were strongly associated with sole disorder, although the
      combination of lactation stage from 61 to 120 d post partum in cows of other dual
      purpose breeds was positively associated with the presence of sole ulcer in one
      leg only in first parity cows. The time of year for claw trimming was a risk
      factor for acute haemorrhage in first parity cows, with the period from December
      to January most strongly associated with acute haemorrhage. Previous disease
      treatment was a risk factor for sole ulcer in two or more legs in second and
      later parities. Udder related disorders and disorders other than reproductive
      problems were positively associated with the occurrence of sole ulcer. Body
      weight at calving was associated with acute haemorrhage in cows in second and
      subsequent parities. Body weight lower than the mean herd level by > 50 kg was
      negatively associated with acute haemorrhage.

PMID- 9627838
TI  - Changes in electrical conductivity and somatic cell count between milk fractions
      from quarters subclinically infected with particular mastitis pathogens.
AB  - Cows with subclinical intramammary infections were identified by milk
      bacteriology. The mastitis pathogens included Staphylococcus aureus (n = 9),
      Streptococcus uberis (n = 10) and coagulase-negative staphylococci (n = 10).
      Samples of first fore milk, main flow milk and strippings milk fractions were
      collected from each quarter and laboratory measurements were made of electrical
      conductivity, milk fat concentration and somatic cell count. Conductivity
      measurements were corrected for milk fat concentration and within-cow inter
      quarter conductivity ratios calculated. Repeatability estimates of all
      measurements between days were calculated. In the case of infected quarters, all
      conductivity values decreased markedly (P < 0.05) from first fore milk to main
      flow milk fractions. Conductivity differences between quarters of infected cows
      were substantially lower during the main milk flow phase. For quarters infected
      with Staph. aureus an increase in conductivity was observed (P < 0.05) from main
      flow to strippings fractions. For uninfected quarters, conductivity declined as
      milk fat concentration increased with successive milk fractions. Variation, both
      within and between milk fractions, was greater for somatic cell count than for
      conductivity. Differences in conductivity between milk fractions from individual
      infected quarters were not accounted for by changes in fat concentration and may
      result from the mixing of milk from infected and uninfected regions of the gland.
      Localized infection may produce a decrease in conductivity between fore milk and
      mid-flow fractions while differential drainage from an infection site in the
      secretory tissue may additionally produce an increase in conductivity from mid
      flow to strippings fractions. Such changes may thus provide information on the
      location and magnitude of an infection. The results clearly demonstrate the
      importance of the milk fraction when using conductivity as a diagnostic of
      intramammary infection, the highest diagnostic sensitivity being achieved by
      using first fore milk samples.

PMID- 9627839
TI  - Characteristics of L-glutamine transport by lactating mammary tissue.
AB  - The transport of L-glutamine by the lactating rat mammary gland has been
      investigated using rat mammary tissue explants and the in situ perfused rat
      mammary gland. L-glutamine uptake by both explants and the perfused mammary gland
      was via both Na(+)-dependent and Na(+)-independent pathways. It appeared that
      these pathways are situated on the blood-facing aspect of the mammary gland. L
      glutamine uptake by both mammary preparations was markedly inhibited by 2
      aminobicyclo[2,2,1]heptane-2-carboxylic acid in the absence of external Na+. This
      is consistent with L-glutamine uptake via system L. The Na(+)-dependent
      component(s) of L-glutamine uptake remains to be precisely identified. However,
      system A can be ruled out on the basis that L-glutamine was not inhibited by
      (methylamino)isobutyric acid. Mammary tissue concentrates L-glutamine with
      respect to both milk and plasma: we suggest that the Na(+)-dependent component(s)
      of L-glutamine uptake is responsible for generating the intracellular to
      extracellular concentration gradient.

PMID- 9627840
TI  - Sequence analysis of Camelus dromedarius milk caseins.
AB  - Alpha s1-, alpha s2-, beta- and kappa-caseins from Somali camels (Camelus
      dromedarius) were purified by acid precipitation at pH 4.4, crudely separated
      into an alpha-CN and a beta-CN fraction and further purified by reversed-phase
      HPLC. Fragments of tryptic digests were sequenced. Amino acid patterns obtained
      were used to screen a cDNA library constructed from mRNA from lactating udder
      tissue. Full length clones corresponding to the four caseins were sequenced. The
      numbers of residues in the sequences deduced were alpha s1-CN 207, alpha s2-CN
      178, beta-CN 217, kappa-CN 162. Percentage similarity to bovine proteins was
      alpha s1-CN A 39, alpha s2-CN 56, beta-CN 64, kappa-CN 56. Acid-precipitated
      casein of pooled milk was separated by reversed-phase HPLC and monitored at 220
      nm, and its composition, estimated from peak integration, was (g/kg total casein)
      alpha s1-CN 220, alpha s2-CN 95, beta-CN 650, kappa-CN 35. Degrees of
      phosphorylation and glycosylation were determined by laser ionization mass
      spectrometry and sequence pattern analysis. Molecular masses determined were
      (kDa) alpha s1-CN A, 24.755 and 24.668; alpha s1-CN B, 25.293; alpha s2-CN
      21.993; beta-CN, 24.900; kappa-CN 22.294-22.987. The pH values of the most
      probable isoelectric points were: alpha s1-CN A 6P 4.41, alpha s1-CN B 6P 4.40,
      alpha s2-CN 9P 4.58, beta-CN 4P 4.66, kappa-CN 1P, with ten sialic acid residues
      bound, 4.10.

PMID- 9627841
TI  - Biochemical characterization of bovine alpha s1-casein F and genotyping with
      sequence-specific primers.
AB  - Bovine alpha s1-casein F (alpha s1-CN F) was found in a genetic resource of
      Deutsches Schwarzbuntes Niederungsrind cows at a frequency of 0.009. Biochemical
      characterization of this new variant was obtained by automated sequencing of
      reversed-phase HPLC-separated tryptic peptides of alpha s1-CN F and alpha s1-CN
      B. alpha s1-CN F was found to be a subtype of alpha s1-CN B with a single amino
      acid substitution (SerP/Leu) in position 66. DNA sequencing revealed a C/T
      transition in position 8418 of the gene. Sequence-specific primers were designed
      to perform an allele-specific polymerase chain reaction for detection of alpha s1
      CnF. Typing of artificial insemination sperm samples included in the genetic
      resource sperm pool identified one sire heterozygous for alpha s1 CnF.

PMID- 9627842
TI  - Proteolytic specificity of chymosin on caprine alpha s1-caseins A and F.
AB  - From hydrolysis experiments carried out on alpha s1-caseins A and F at pH 5.2 in
      the presence of 30 g NaCl/l, i.e. the conditions encountered in many young goats'
      cheeses, it was found that minima of 19 and 9 bonds were sensitive to chymosin in
      variants A and F respectively. Variant A was hydrolysed faster than variant F and
      the proteolytic pattern (reversed-phase HPLC and polyacrylamide agarose gel
      electrophoresis) differed between the variants. Hydrolysates from both variants
      had a number of cleavage sites in common (Leu20-Leu21, Phe23-Ala24 and Phe32
      Arg33 in both variants, Leu101-Lys102 and Leu64-Lys65, Leu120-His121 and Leu83
      His84, Leu142-Ala143 and Leu105-Ala106, Leu149-Phe150 and Leu112-Phe113, Leu156
      Asp157 and Leu119-Asp120, Trp164-Tyr165 and Trp127-Tyr128 in variants A and F
      respectively), while other bonds were split only in variant A (Leu16-Asn17, Glu18
      Asn19, Phe28-Pro29, Ile44-Gly45, Tyr80-Ile81, Gln82-Lys83, Tyr91-Leu92, Tyr94
      Leu95, Leu109-Glu110 and Phe179-Ser180). Major cleavage sites appeared to be at
      Phe23-Val24, Leu142-Ala143 and Trp164-Tyr165 for variant A, and Phe23-Val24 and
      Leu64-Lys65 for variant F. Cleavage site Phe23-Val24 could be the origin of the
      first breakdown product from goat alpha s1-caseins A and F visible in
      polyacrylamide agarose gel electrophoresis.

PMID- 9627843
TI  - Identification of C-terminally truncated forms of beta-lactoglobulin in whey from
      Romagnola cows' milk by two dimensional electrophoresis coupled to mass
      spectrometry.
AB  - Four minor protein components were detected in whey from Romagnola cows' milk by
      polyacrylamide gel isoelectric focusing and two dimensional gel electrophoresis.
      Individual protein spots were transferred by electroblotting on to a
      polyvinylidene difluoride membrane and isolated by cutting out the relevant area.
      After in situ trypsinolysis, a portion of the digest was analysed directly by
      matrix-assisted laser desorption ionization-time of flight mass spectrometry. The
      mass profile allowed us to establish a correlation between beta-lactoglobulins A
      and B and the four minor whey protein components. They were identified as C
      terminally truncated beta-lactoglobulin A and B variants with missing N-terminal
      peptides, beyond residues in the range 100-123 and 136-147 respectively. Two of
      the minor components were related to beta-lactoglobulin A and two to beta
      lactoglobulin B.

PMID- 9627844
TI  - Influence of thermal and other manufacturing stresses on retinol isomerization in
      milk and dairy products.
AB  - An analytical procedure, based upon HPLC, has been used to determine the degree
      of isomerization of retinol (vitamin A) in various dairy products. In raw milks,
      which are not subjected to thermal processing, there was no conversion of the
      predominant all-trans-isomers to cis-isomers in samples from various species.
      Pasteurized milks with mild heat treatment (high quality milk) had an average 13
      cis: all-trans ratio of 2.6%, while pasteurized milk treated for 15 s at
      temperatures ranging from 72 to 76 degrees C had an average ratio of 6.4%. Milk
      subjected to more severe heat treatments had a higher degree of isomerization
      (UHT milk, 15.7%; sterilized milk, 33.5%), consistent with increased thermal
      conversion of the retinol isomers. In pasteurized and UHT cream, the increase in
      13-cis-isomer was also a consequence of heat treatment (pasteurized cream, 3.0%;
      UHT cream, 14.4%). The presence of cis isomers in fermented milk suggests that
      fermentation processes, directly or indirectly, can induce cis-trans
      isomerization. In the cheeses analysed, the extent of retinol isomerization
      ranged from 7.6 to 35.0%. Our results confirm the importance of individual
      isomers in evaluating the vitamin A status of dairy products.

PMID- 9627845
TI  - Mechanism and kinetics of inactivation at 40-70 degrees C of the extracellular
      proteinase from Pseudomonas fluorescens 22F.
AB  - HPLC size exclusion chromatography experiments showed that during inactivation at
      40-70 degrees C of the extracellular proteinase from Pseudomonas fluorescens 22F
      small molecular mass fragments were formed, indicating that autoproteolysis was
      at least one of the major causes of inactivation. The formation of small
      molecular mass fragments and the reaction order indicated that intermolecular
      autoproteolysis was more likely than intramolecular autodigestion. This was
      confirmed by computer simulations. The rate constants and the activation enthalpy
      (delta H++) and entropy (delta S++) for the reactions of the intermolecular
      autoproteolysis model were derived from computer simulations. delta H++ and delta
      S++ of the unfolding reaction were 504 kJ mol-1 and 1252 J mol K-1 respectively.
      delta H++ and delta S++ of the refolding reaction were strongly temperature
      dependent. The estimates for the enthalpy (delta H0) and entropy (delta S0)
      difference between the folded and unfolded state as derived from the reaction
      rate constants of unfolding and refolding were subject to large deviations, owing
      to accumulation of errors in the estimation of the kinetic characteristics.

PMID- 9627846
TI  - Behaviour and enterotoxin production by Staphylococcus aureus during the
      manufacture and ripening of raw goats' milk lactic cheeses.
AB  - To study the possible presence of staphylococcal enterotoxin A in raw goats' milk
      lactic cheese, milk was inoculated with an enterotoxigenic Staphylococcus aureus
      strain to a final concentration of 4, 5 and 6 log(cfu/ml). Cheese was prepared
      following industrial specifications and ripened for 42 d. Detection of the
      enterotoxins was by the Vidas Staph enterotoxin test (BioMerieux) and by an
      indirect double-sandwich ELISA technique using anti-enterotoxin monoclonal
      antibodies. Staphylococcal counts declined markedly after draining, and by the
      end of ripening they had disappeared from some cheeses. In contrast, aerobic
      mesophilic organisms grew well. The level of staphylococcal enterotoxin A
      recovered varied from 1 to 2.5 ng/g cheese made with an initial population of
      10(5) or 10(6) cfu/ml. Only traces of enterotoxin A (0.5 ng/g) were detected in
      cheeses made with the lowest Staph. aureus inoculum used in this study.
      Enterotoxin A was also detected in cheeses from which Staph. aureus had
      disappeared.

PMID- 9627847
TI  - Bovine lactoferrin induces both mucosal and systemic immune response in mice.
AB  - Lactoferrin (Lf) is a milk iron-binding glycoprotein that plays a role in iron
      transport and acts as both a bacteriostatic and a growth modulating agent. The
      aim of this study was to investigate the nature of immune responses induced by
      repeated oral administration of bovine milk Lf in mice. Groups of ten female
      BALB/c mice were fed daily for 4 weeks with two doses of protein antigen: a low
      (0.05 mg/g body weight per d) or high (1 mg/g body weight per d) dose of Lf, or
      water as a control. A fourth group was immunized intramuscularly with 0.01 mg Lf
      in complete Freund's adjuvant. Anti-Lf IgA and IgG were detected in the
      intestinal fluid and serum of mice given Lf. Total immunoglobulins were higher in
      the intestinal fluid in Lf groups than in the control group. No difference could
      be detected in the serum. IgA and IgG secretion was enhanced in Peyer's patches
      and spleen from Lf-fed mice, in comparison with controls. [3H]thymidine uptake
      into Peyer's patch and spleen cells from both control and Lf-fed mice was
      enhanced by 75 micrograms Lf/ml in vitro, but Lf groups had a greater
      proliferation rate than the control group. These findings suggested that Lf could
      act as an immunostimulating factor on the mucosal immune system and that
      activation of the mucosal immune system is dependent on the ability of Lf to bind
      to the intestinal mucosa.

PMID- 9627849
TI  - Effect of various milking machine systems and components on free fatty acid
      levels in milk.

PMID- 9627848
TI  - Effect of lactation stage on the cheesemaking properties of milk and the quality
      of Saint-Nectaire-type cheese.
AB  - Two groups of eight multiparous cows with different calving periods (November or
      February) were managed in the same way during lactation. During four 4 week
      experimental periods distributed over 12 months, the cows were fed on a diet
      composed of hay and concentrate (70:30) in a restricted and controlled amount
      which varied according to their lactation stage, so as to cover the animals'
      requirements correctly. The animals' average lactation stage varied according to
      period from 26 to 298 d. Milk from each group was processed on two occasions
      during each period to make Saint-Nectaire-type cheese; the cheesemaking
      conditions were the same throughout. Lactation stage had an important effect on
      milk fat, protein and calcium contents but not on the casein: protein ratio or
      phosphorus content. The milk pH and the urea content were higher in late
      lactation. The calcium concentration of milk was higher in late lactation but the
      soluble fraction was higher in early lactation. Despite higher protein contents,
      the maximal firmness of the coagulum of late-lactation milk was not different
      from that of early or mid-lactation milks. pH was higher in cheeses from late
      lactation milks compared with those from early and mid-lactation milks. Cheeses
      from early lactation milks were more yellow than the others and had a lower dry
      matter fat content. In sensory analysis the odour of cheeses from early and late
      lactation milks was less pleasant than that of those from mid-lactation milks.
      Cheeses from late-lactation milks were more melting and less firm than those from
      early or mid-lactation milks. Their taste was more intense and more persistent.
      At tasting, they were less appreciated than the others. These differences were
      linked to increased proteolysis in the cheeses made with late-lactation milks.

PMID- 9627850
TI  - Restriction fragment length polymorphisms at the ornithine decarboxylase locus
      associated with milk protein yield in Holsteins.

PMID- 9627851
TI  - Effect of protein content on low temperature inactivation of the extracellular
      proteinase from Pseudomonas fluorescens 22F.

PMID- 9627852
TI  - Glaucoma screening.

PMID- 9627853
TI  - Influence of acquisition parameters on hemodynamic measurements with the
      Heidelberg Retina Flowmeter at the optic disc.
AB  - PURPOSE: The Heidelberg Retina Flowmeter (HRF; Heidelberg Engineering GmbH,
      Heidelberg, Germany) is a new instrument that determines hemodynamic variables at
      discrete locations of the retina and the optic disc. The objective of this study
      was to evaluate the influence of various HRF recording settings on the long-term
      variability of the HRF parameter. "Flow," computed at the optic nerve head in
      healthy individuals. METHODS: The authors obtained 2 sets of 5 HRF recordings in
      10 healthy individuals (age range, 23-60 years). The HRF recordings were obtained
      within a scan area of 10 degrees x 2.5 degrees (set 1) and 20 degrees x 5 degrees
      (set 2). For each set, the HRF recordings were obtained on 5 consecutive days.
      Respective HRF recordings for both sets were obtained on the same days. On these
      recordings, the HRF parameter, "Flow," was computed at 3 different regions of
      interest (temporal superior, temporal inferior, and temporal rim of the optic
      disc). At all three locations, Flow was computed within windows of measurement of
      10 pixels x 10 pixels and 20 pixels x 20 pixels. The effect of larger windows (30
      pixels x 30 pixels, 40 pixels x 40 pixels, and 50 pixels x 50 pixels) was tested
      at the temporal rim of the optic disc. RESULTS: The highest reliability
      coefficient was reached with a scan area of 20 degrees x 5 degrees at the
      temporal superior rim of the optic disc (r = 0.93). Within a scan area of 20
      degrees x 5 degrees, the size of the user-defined measuring window did not
      influence the reliability. Two models of analysis of variance disclosed that the
      only effect on the computed value of Flow that reached statistical significance
      was that because of the scan area (F = 11.172; p = 0.001). The location of the
      window of measurement and its size had no statistically significant effect.
      CONCLUSION: The present results show that the location of the window of
      measurement has an important effect on the long-term variability of the HRF
      parameter, Flow. In addition, different scan areas influence significantly the
      computed values of this parameter.

PMID- 9627854
TI  - The efficacy of the dicon screening field to detect eyes with glaucomatous field
      loss by Humphrey threshold testing.
AB  - PURPOSE: The authors compare the results of the Dicon suprathreshold, kinetic
      fixation perimeter with multiple stimulus presentation to automated threshold
      perimetry (Humphrey) in the same eye. METHODS: A Dicon screening visual field
      test and a Humphrey threshold visual field test were performed in 148 eyes of 148
      persons with glaucoma or who were suspect for glaucoma. The number and pattern of
      missed points on the Dicon test were compared with Humphrey global indices in
      each eye. RESULTS: The median time to complete the 40-point, Dicon suprathreshold
      test was 2.7 minutes per eye. Regression analyses indicated that Dicon test
      parameters were modestly correlated with Humphrey corrected pattern standard
      deviation (CPSD) probability and mean deviation (R2 ranging from 0.21 to 0.46, p
      = 0.000). With glaucoma defined as a Humphrey Glaucoma Hemifield Test (GHT)
      result of outside normal limits, the best mix of sensitivity and specificity of
      Dicon results occurred at 2 or more missed points, with sensitivity of 64% and
      specificity of 83%. The specificity was maximum (90%) with a Dicon criterion of 3
      or more adjacent missed points, but sensitivity at this level was 55%. With
      glaucoma defined by CPSD probability value less than 1%, sensitivity and
      specificity for two adjacent missed Dicon points were 69% and 87%, respectively.
      CONCLUSION: Dicon suprathreshold testing is a practical means to differentiate
      between some persons with glaucomatous damage and glaucoma suspects.

PMID- 9627855
TI  - Changing definition of glaucoma.
AB  - OBJECTIVE: The authors assess whether there has been a change in the definition
      of open-angle glaucoma (OAG) in peer-reviewed articles during the past 15 years.
      METHODS: A literature review was conducted (via Medline) to identify all articles
      on OAG from the American Journal of Ophthalmology, Ophthalmology, and Archives of
      Ophthalmology for the years 1980, 1985, 1990, and 1995. One hundred eighty-two
      articles were reviewed to identify optic nerve, visual field, and intraocular
      pressure (IOP) criteria used to define glaucoma. Articles were classified and
      analyzed by study design, severity, and type of glaucoma. RESULTS: Of the 182
      articles, 120 (66%) included a definition of OAG. Among these, approximately 36%
      used both optic disc and visual field criteria, 13% used optic disc or visual
      field criteria, 26% used only visual field criteria, 20% used only IOP, and 5%
      used only optic disc criteria. In the 1980s, when both disc and/or field
      parameters were used in the definition, 74% of the publications used general
      qualitative statements such as "characteristic glaucomatous changes." In the
      1990s, 34% of articles provided specific descriptions of the optic disc and 61%
      provided specific visual field criteria. A similar proportion of reviewed
      articles published in the 1980s (20.4%) and 1990s (19.7%) used IOP as its sole
      criterion for defining glaucoma. A significantly larger proportion of prospective
      studies (38/46; 83%) provided specific criteria to define glaucoma compared to
      cross-sectional (67/111; 60%) and retrospective studies (15/25; 60%). CONCLUSION:
      There is a lack of consistency in how glaucoma is defined in current clinical
      research. Although recent studies provide more specific criteria, there is a need
      to obtain a consensus definition.

PMID- 9627856
TI  - The effect of paclitaxel powder on glaucoma filtration surgery in rabbits.
AB  - OBJECTIVE: The authors determine if the intraoperative placement of paclitaxel
      powder in the subconjunctival space improves the outcome of glaucoma filtration
      surgery in rabbits. METHODS: A posterior lip sclerectomy was performed in the
      right eye of 24 New Zealand white rabbits. Before the conjunctiva was fully
      sutured, 8 mg of mannitol powder alone, or 8 mg of mannitol powder containing
      either 10 micrograms or 250 micrograms of paclitaxel, was placed in the
      subconjunctival space of six eyes each in masked fashion. An additional six
      animals were treated with episcleral application of a sponge soaked in a solution
      of 0.5 mg/ml of mitomycin C (MMC) for 5 minutes before the sclerectomy was
      performed. Intraocular pressure and bleb size were measured until the operation
      had failed or until the 7 weeks of observation had concluded. RESULTS: Both
      paclitaxel powder and MMC solution improved the outcome of filtration surgery in
      this model as measured by magnitude of intraocular pressure (IOP) lowering and
      duration of surgical success. No toxic effect of either drug was observed,
      although endophthalmitis was observed in eight animals followed for more than 3
      weeks. CONCLUSION: The introduction of paclitaxel into the subconjunctival space
      at the conclusion of filtration surgery has an effect comparable to
      intraoperative MMC.

PMID- 9627857
TI  - Cataract and exfoliative glaucoma.

PMID- 9627858
TI  - Early detection of glaucoma.

PMID- 9627859
TI  - Comparative glaucomatology. I: The spontaneous glaucomas.

PMID- 9627860
TI  - Ophthalmic drug development: procedural considerations.

PMID- 9627861
TI  - Current and future approaches to glaucoma screening.

PMID- 9627863
TI  - Reliability of manual skinfold tests in a healthy male population.
AB  - OBJECTIVE: To assess the intra- and interexaminer agreement of a manual skinfold
      thickness test and a manual skinfold compliance test. The relation between the
      weekly routine of the examiners and the intraexaminer reliability was also
      assessed for both tests. DESIGN: This is a reliability study of a common
      palpatory procedure to assess skinfold thickness and skinfold compliance. Twelve
      healthy subjects were palpated twice in two sessions by 12 examiners. SETTING:
      The study was conducted at the Polytechnic of Utrecht (the Netherlands), Faculty
      of Health Care, Department of Physiotherapy. SUBJECTS: Healthy male subjects
      recruited from students of the Polytechnic of Utrecht (the Netherlands),
      Department of Physiotherapy. RESULTS: The intraexaminer agreement Intraclass
      Correlation Coefficient [ICC(3.1)] was .25 for skinfold thickness and .28 for
      skinfold compliance. The interexaminer agreement [ICC(2,1)] ranged from .01 to
      .24. The Pearson correlation coefficient between the examiners age and routine
      vs. intraexaminer agreement ranged from -.41 to .23 (nonsignificant).
      CONCLUSIONS: The intra- and interexaminer agreement of the manual skinfold test
      produced poor-to-fair reliability. The correlation between the examiners' weekly
      routine and the intraexaminer reliability ranged from low negative to little (if
      any). This study shows a lack of reliability of palpatory tests for skinfold
      thickness and skinfold compliance. This outcome agrees with results of previous
      studies found in the literature.

PMID- 9627862
TI  - Comparative efficacy of conservative medical and chiropractic treatments for
      carpal tunnel syndrome: a randomized clinical trail.
AB  - OBJECTIVE: To compare the efficacy of conservative medical care with chiropractic
      care in the treatment of carpal tunnel syndrome. DESIGN: Two-group, randomized,
      single-blind trial with 9 wk of treatment and a 1-month follow-up interview.
      SETTING: Wolfe-Harris Center for Clinical Studies at Northwestern College of
      Chiropractic in Bloomington, Minnesota. PATIENTS: Ninety-one of 96 eligible
      subjects who reported symptoms that were confirmed by clinical exam and nerve
      conduction studies. INTERVENTIONS: Interventions included ibuprofen (800 mg 3
      times a day for 1 wk, 800 mg twice a day for 1 wk and 800 mg as needed to a
      maximum daily dose of 2400 mg for 7 wk) and nocturnal wrist supports for medical
      treatment. Chiropractic treatment included manipulation of the soft tissues and
      bony joints of the upper extremities and spine (three treatments/week for 2 wk,
      two treatments/week for 3 wk and one treatment/week for 4 wk), ultrasound over
      the carpal tunnel and nocturnal wrist supports. MAIN OUTCOME MEASURES: Outcome
      measures were pre- and postassessments of self-reported physical and mental
      distress, nerve conduction studies and vibrometry. RESULTS: There was significant
      improvement in perceived comfort and function, nerve conduction and finger
      sensation overall, but no significant differences between groups in the efficacy
      of either treatment. CONCLUSIONS: Carpal tunnel syndrome associated with median
      nerve demyelination but not axonal degeneration may be treated with commonly used
      components of conservative medical or chiropractic care.

PMID- 9627864
TI  - The effects of x-axis vertebral translation on projected y-axis vertebral
      rotation.
AB  - BACKGROUND: Few studies have quantified the projection/distortion errors that
      occur in anteroposterior (AP) radiographs. OBJECTIVES: To quantify the
      projection/distortion errors on AP radiographs caused by lateral translation of
      the vertebrae. To demonstrate the effect of vertebral shape on projection errors.
      STUDY DESIGN: Three models of increasing complexity were constructed to document
      the distortion. Model 1 consisted of three metal pins embedded in a piece of
      metal tubing that was X-rayed in three positions. Model 2, a simple model of the
      X-ray beam mounted on a wooden platform, allowed for translation of a vertebral
      model in a simulated X-ray beam and the measurement of projected points of
      contact between the model and rays of the simulated beam. Model 3 is a computer
      simulation of the X-ray beam in which a vertebral model was translated laterally
      to varying locations. The projected points of contact between the simulated rays
      and the vertebral body margins and lamina junction were measured. Model 3 also
      showed that vertebral body shape has a large effect on the projected axial
      rotation. Two other simple models were created and discussed in relation to shape
      dependent projection errors. RESULTS: X-axis translation results in projected y
      axis rotation. Increasing magnitudes of x-axis vertebral translation results in
      increasing magnitudes of projected y-axis vertebral rotation. The projected
      rotation is also influenced by vertebral shape. CONCLUSION: We have shown that
      three-dimensional lateral translation projects as axial rotation on the AP
      radiograph. Projection error is largely influenced by the shape of the object and
      by the increasing obliquity of the rays of the X-ray beam. This would seemingly
      create confusion and invalidate spinal listings of vertebral position obtained
      from the AP radiographic image.

PMID- 9627865
TI  - The reliability of measuring active and passive cervical range of motion: an
      observer-blinded and randomized repeated-measures design.
AB  - PURPOSE: To study the intra- and interexaminer reliability of measuring active
      and passive cervical range of motion (ROM). STUDY DESIGN: Observer-blinded,
      randomized repeated measures of active or passive cervical ROM by two different
      examiners. SETTING: Institute of Medical Biology (Center of Biomechanic) at
      Odense University. PARTICIPANTS: Forty asymptomatic students, 20 of each gender,
      aged 20 to 30 yr, from the University of Odense. INTERVENTION: Measurements of
      either active or passive cervical ROM using the electrogoniometer CA-6000 Spine
      Motion Analyzer by two blinded examiners. Each subject was measured four times,
      twice by each examiner in random order, using a mean-of-three-measurements
      protocol. MAIN OUTCOME MEASURES: The reliability within and between examiners in
      active and passive ROM was assessed by the Intraclass Correlation Coefficient
      [ICC (2,k)]. Coefficient of variation (CV) was used to assess the reproducibility
      within and between examiners in active and passive ROM. RESULTS: Intraexaminer
      ICCs for active ROM ranged from .81 to .97 and for passive ROM from .85 to .98.
      The interexaminer ICCs for active ROM ranged from .76 to .98 and for passive ROM
      from .65 to .95. Intraexaminer CVs for active ROM ranged from 2.42 to 10.93 and
      for passive ROM, from 1.82 to 5.77. The interexaminer CVs for active ROM ranged
      from 2.30 to 14.43 and for passive ROM, from 2.58 to 10.93. CONCLUSION: Active
      and passive ROM could be measured reliably in six movement directions by the same
      examiner. Measurements were reliable when measured by different examiners for
      active cervical ROM in six movement directions and passive total ROM in three
      motion planes.

PMID- 9627866
TI  - Informed consent: an Australian case study.
AB  - OBJECTIVE: Informed consent, as practiced in Australian chiropractic practice,
      was explored by means of a collective case study. DESIGN: Twenty-one chiropractic
      practices were visited and 25 chiropractor-patient units explored. Purposive
      sampling of practitioners was undertaken using a maximum variation strategy.
      Convenience sampling of patients was performed within each participating
      practice. Data was gathered from each chiropractor-patient unit, consisting of
      one practitioner and usually five patients, by means of practitioner interview,
      patient questionnaire and interview and, in certain cases, practice observation.
      Thematic analysis of the interviews were correlated with information derived from
      the patient questionnaires and validated by selective practice observation. Data
      was compared within and across chiropractor-patient units. RESULTS: Consent for
      chiropractic care was usually implied. Chiropractors in this study seldom
      obtained formal verbal, and never written, informed consent. New chiropractic
      patients were nonetheless informed about the procedures that the chiropractor
      intended to perform, and their acquiescence was taken as consent. Participants
      seldom discussed the potentially serious consequences of chiropractic adjustment
      but did actively attempt to identify and avoid exposing at-risk patients.
      Patients were often counseled about potential muscle soreness after the
      chiropractic adjustment. The behavior of chiropractors in this study was
      consistent with their patients' expectations. CONCLUSION: This study suggests
      that chiropractic behavior in Australian clinical practice meets the moral, but
      not all of the legal, requirements for informed consent.

PMID- 9627867
TI  - Carpal tunnel syndrome: conservative and nonconservative treatment. A
      chiropractic physician's perspective.
AB  - OBJECTIVE: To discuss the treatment of carpal tunnel syndrome (CTS) including
      indications for referral to medical evaluation and/or comanagement. DATA SOURCE:
      More than 200 articles published in the health care literature from 1963 to 1997
      and indexed on Medline concerning conservative and surgical intervention for CTS.
      Indexing terms used were "Carpal Tunnel," combined with keywords "Conservative"
      and "Surgery." STUDY SELECTION: Reports involving either conservative or non
      conservative treatment for CTS or original descriptive reports of surgical
      techniques of carpal tunnel release. DATA EXTRACTION: Indications and
      contraindications for each conservative and surgical option. Concise and general
      descriptions of manual, medical and surgical interventions in current use,
      including summaries of the benefits and risks of each treatment. DATA SYNTHESIS:
      The review is presented as a discussion of diagnostic technique and conservative
      and surgical treatments for CTS currently used in North America. CONCLUSIONS:
      Recommendations are that CTS, accompanied by demyelination but without axonal
      degeneration, can be treated initially with conservative medical or manual
      procedures.

PMID- 9627868
TI  - A conservative approach for a patient with traumatically induced urinary
      incontinence.
AB  - OBJECTIVE: To consider a conservative management plan for a patient suffering
      from diurnal enuresis. CLINICAL FEATURES: A 12-yr-old girl complained of left
      flank pain and involuntary urine loss that apparently began a short time after
      she fell backwards and landed on her coccyx. She had to wear a sanitary pad
      prophylactically throughout each day for more than a year because of
      unpredictable urinary incontinence. INTERVENTION: Manual adjusting procedures and
      soft tissue therapy were applied initially. Procedures were modified later to
      include an intrarectal technique. The quantity of urine loss decreased slowly
      with the initial treatment approach but never resolved completely. The flank pain
      also decreased somewhat but never ceased altogether. After the introduction of
      the intrarectal technique, additional progress was reported and both the flank
      pain and urinary incontinence resolved completely. A 4-yr follow-up confirmed
      complete resolution. CONCLUSION: Conservative care helped an adolescent girl
      suffering from traumatically induced urinary incontinence.

PMID- 9627869
TI  - Shifts in approaches to continuing professional development: implications for the
      chiropractic profession.

PMID- 9627870
TI  - Side effects of chiropractic treatment: a prospective study.

PMID- 9627871
TI  - Movements of vertebrae during manipulative thrusts to unembalmed human cadavers.

PMID- 9627872
TI  - Unilateral vs bilateral strabismus surgery for exotropia.

PMID- 9627873
TI  - Clinical characteristics of surgically treated adult strabismus.
AB  - BACKGROUND: Strabismus is present in approximately 4% of the population with most
      forms becoming clinically evident in infancy and childhood. Adult strabismus,
      including that resulting from recurrent childhood deviations, varies in etiology,
      presentation, symptomatology, and response to treatment. This report is intended
      to prospectively characterize adults who required surgical correction of their
      strabismic deviation. METHODS: Beginning in 1991, a prospective computerized
      database was collected that contained all clinical, laboratory, and surgical
      information on the adult ocular motility service at the Scheie Eye Institute and
      The Children's Hospital of Philadelphia (Philadelphia, Pa). Analysis of those
      patients who underwent surgical correction of their strabismus is included in
      this report. Demography, clinical characteristics, and surgical procedures
      including results were analyzed separately in adults with their strabismus
      beginning before visual maturation (BVM) (9 years of age) and after visual
      maturation (AVM). RESULTS: A minimum of 6 months and average of 1.8 years follow
      up is reported on 262 procedures in 255 patients with an average age of 37
      between January 1991 and January 1996. Sixty-two percent of patients had their
      strabismus onset BVM. Fifty-one percent of BVM patients and 80% of AVM patients
      had incomitant deviations. Adjustable suture surgery was performed on 97% of all
      patients, with 28% of BVM and 57% of AVM patients having multiplanar surgery.
      Successful motor alignment was achieved in 85% of all patients after one surgical
      procedure. Sensory success was achieved in 81% of all AVM patients and 25% of all
      BVM patients. Subjective success was 94% in both groups of patients. CONCLUSIONS:
      Numerous differences exist between childhood and adult strabismus characteristics
      and response to surgery. Although strabismus surgery is effective, differences in
      results reflect the varied physiology regarding etiology, pathophysiology, and
      symptomology. Classification into AVM and BVM groups will provide continued
      clarity for future studies.

PMID- 9627874
TI  - Early and late postoperative alignment following unilateral lateral rectus
      recession for intermittent exotropia.
AB  - PURPOSE: Bilateral lateral rectus recession is useful in the treatment of
      intermittent exotropia. A unilateral recession may be used in the treatment of
      small-to-moderate angle intermittent exotropia as well. An early overcorrection
      following bilateral surgery has been shown to carry the best prognosis for future
      alignment. The relationship between the early and late postoperative alignment
      following unilateral surgery is unknown. The current study was designed to
      establish this relationship. METHODS: Thirty-seven patients undergoing a
      unilateral lateral rectus recession for intermittent exotropia were prospectively
      evaluated to determine the relationship between early and late postoperative
      alignment. Patients were evaluated 1 week and 6 months following surgery. A
      satisfactory result was considered to be alignment within 8 prism diopters
      (delta). RESULTS: Of the 37 patients who underwent surgery, 35 completed the
      study. Overall, 77% of patients achieved a satisfactory result at the 6-month
      exam (27/35). Satisfactory alignment at 6 months was obtained in all patients who
      were orthophoric (14/14), 77% (10/13) of patients with an exodeviation less than
      9 delta (10/13), and 60% (3/5) of patients with an exodeviation less than 9 delta
      at the 1-week postoperative exam. Twenty-nine percent of patients changed
      alignment status during this time period (10/35), and 29% of all patients became
      more divergent (10/35). The average divergent shift for the entire group was 1.6
      delta and was not significant. Among those patients who experienced a divergent
      shift, the average amount was 6 delta. CONCLUSIONS: There is not a significant
      difference in early versus late alignment following unilateral lateral rectus
      recession. Surgeons performing this procedure should not expect a significant
      divergent shift from the first postoperative week. Unlike bilateral recessions
      where an early overcorrection is desirable, acceptable alignment in the first
      week following surgery carries the best prognosis for later alignment.

PMID- 9627875
TI  - Treatment of congenital adduction palsy with synergistic divergence.
AB  - OBJECTIVE: To report on successful management of congenital adduction palsy with
      synergistic divergence by performing weakening surgery on the superior and
      inferior oblique muscles. METHODS: We performed a total tenotomy of the lateral
      rectus muscle, followed by resection of the medial rectus muscle and tenotomy of
      the superior oblique and myectomy of the inferior oblique muscles in a patient
      who had congenital adduction palsy with synergistic divergence. RESULTS: Total
      tenotomy of the lateral rectus muscle had no effect on synergistic divergence,
      resection of the medial rectus muscle reduced it to some extent and tenotomy of
      the superior oblique and myectomy of the inferior oblique muscles further reduced
      this phenomenon. The improvement in synergistic divergence was maintained at 2
      1/2 years later at follow up. CONCLUSIONS: Weakening surgery on the superior and
      inferior oblique muscles should be considered in the management of synergistic
      divergence.

PMID- 9627876
TI  - Reduction in binocular enhancement of the visual-evoked potential during
      development accompanies increasing stereoacuity.
AB  - PURPOSE: To study the maturation of normal binocular vision. METHODS: Binocular
      visual function has been studied and monocular and binocular pattern reversal
      visual-evoked potentials (VEP) recorded in 20 normal subjects aged 5 to 43 years.
      RESULTS: Stereoacuity improved significantly between the age of 5 and adulthood.
      Mean stereoacuity for eight children measured by the Titmus test was 61 seconds
      of arc and 56 seconds of arc by the TNO test. For the 12 adults in the study,
      corresponding mean stereoacuities were 45 and 31 seconds of arc. Over the same
      timespan, binocular enhancement of the VEP P100 amplitude decreased. For the
      children aged 5 to 10 years, the mean binocular VEP enhancement to 20' checks was
      1.60, whereas for young adults it was 1.19. There was no comparable change in the
      binocular enhancement to 40' checks, with mean binocular enhancement of 1.31 in
      the children and 1.26 in the young adults. Over the same age range, VEP latency
      also decreased. CONCLUSION: During visual maturation, improvement in stereoacuity
      is accompanied by a fall in binocular enhancement of the P100 amplitude of the
      VEP to small checks and a reduction in the P100 latency.

PMID- 9627877
TI  - Clinical features of pediatric Behcet's disease.
AB  - OBJECTIVE: The aim of this study is to determine the clinical features and
      outcome of Behcet's disease in the pediatric age group. METHOD: Twenty cases
      within a pediatric age group whose ages differ from 5 to 15 years were studied
      retrospectively to determine the age of onset, the initial signs, and the
      progress of the disease. RESULTS: In 18 of the patients whose average age were
      13.3 years (5 to 18 years), the initial symptoms associated with Behcet's disease
      were oral aphtous lesions or genital ulcers. Among them, 16 developed ocular
      symptoms in a later stage, at an average of 15.5 years of age (11 to 18 years).
      Posterior uveitis was the most common manifestation, detected in 75% of the
      cases. Three patients had neurobehcet's disease, and the neurologic
      manifestations were dural thrombosis, pseudotumor cerebri, and quadriparesis.
      CONCLUSIONS: In this study, after an average 4 years' follow up (6 months to 13
      years) the clinical progress of Behcet's disease in the pediatric age group was
      similar to that found in adult disease. Both the ocular signs (i.e., cataracts
      and glaucoma) and the systemic features (i.e., aphtous stomatitis, genital
      ulcers, erythema nodosum, arthritis, and neurologic signs) were manifested at the
      onset or during the progress of the disease.

PMID- 9627878
TI  - Characteristics of a pediatric low-vision population.
AB  - BACKGROUND: Assessment of the causes of childhood blindness is important to
      develop preventive and therapeutic strategies that can reduce the incidence of
      visual impairment. METHODS: A retrospective survey of the clinical records of 395
      consecutive children younger than 14 years of age who were attended by the Low
      Vision Service of State University of Campinas (UNICAMP) was conducted. Data on
      the age distribution, the causes of low vision, the types of low vision aids
      prescribed, the follow up of their use, and improvement in visual acuity were
      obtained. RESULTS: Congenital bilateral toxoplasmic macular scars, optic atrophy,
      and congenital cataracts were the major causes of low vision in this population.
      The optical aid most frequently prescribed was a telescope. The improvement of
      visual acuity with the use of aids was highly significant.

PMID- 9627879
TI  - Extraocular muscle surgery in myotonic dystrophy.

PMID- 9627880
TI  - A new and simple procedure for correction of congenital tarsal kink.

PMID- 9627881
TI  - Nemaline myopathy with severe neonatal hypotonia and total ophthalmoplegia: a
      case report.

PMID- 9627882
TI  - Bilateral lacrimal sac fistulas in a patient with nasopharyngeal non-Hodgkin's
      lymphoma.

PMID- 9627883
TI  - Optic atrophy induced by an intraorbital wooden foreign body: the role of CT and
      MRI.

PMID- 9627884
TI  - Application of cyclopentolate 1% to the medial canthus in children.

PMID- 9627885
TI  - Bilateral hyphemas and cataracts after diode laser retinal photoablation for
      retinopathy of prematurity.

PMID- 9627886
TI  - The provision of dental implants and a fixed prosthesis in the treatment of a
      patient with scleroderma: a clinical report.
AB  - This clinical report highlights some of the problems in providing a suitable
      prosthesis for a patient who suffers from systemic sclerosis. A conventional
      removable partial denture may not have been suitable because of the lack of
      denture bearing area, changing peripheral seal, and insufficient teeth to support
      and retain the denture. An implant-retained FPD overcame these difficulties. One
      would hope that, with regular maintenance and monitoring, quoted prosthesis
      success of 15 years can be achieved.

PMID- 9627887
TI  - Thermoplastic resin used to modify an alveolar orthopedic prosthesis in a patient
      with cleft lip before cheiloplasty: a clinical report.
AB  - Correction of cleft lip and cleft palate is a multidisciplinary team effort.
      Severe bilateral clefts with protruded and rotated premaxillae may complicate
      surgical correction. Prosthetic intervention to reposition segments before
      surgical correction may improve the bony base for tissue molding and avoid excess
      tension at the surgical site. A conventional bulb prosthesis with bonnet and
      straps is often used as an extraoral device to retract a protruded premaxilla for
      severe cleft patients before cheiloplasty. Sometimes, because of lack of
      retention, stability, patient compliance, and controllable forces from a bonnet
      and straps, movement of the premaxillae to a desirable position is difficult to
      achieve. The use of thermoplastic resin to modify a bulb prosthesis as described
      in this clinical report is a simple method to provide good retention for the bulb
      prosthesis and to move a laterally displaced premaxillae to the facial midline.
      The wedging effect created by the thermoplastic resin generated "compressive
      forces" to the premaxilla that was more controllable than the pulling forces
      created by the bonnet and straps therapy. Thermoplastic resin is also a better
      material than a conventional chemically polymerized acrylic resin in dealing with
      an infant's delicate mucosa before cheiloplasty.

PMID- 9627888
TI  - Total maxillary osteoradionecrosis after adjuvant neutron radiotherapy: a
      clinical report.

PMID- 9627889
TI  - In vivo retrospective study of cement thickness under crowns.
AB  - PURPOSE: This study evaluated the cement thickness under crowns cemented with
      zinc phosphate cement that had been in clinical use for at least 10 years.
      MATERIAL AND METHODS: A total of 97 teeth were extracted because of periodontal
      disease as part of a new treatment plan. Teeth were sectioned and the cement
      thickness measured at predetermined points on the occlusal and axial walls with a
      measuring microscope at x150 magnification. RESULTS: Mean cement thicknesses on
      buccal and lingual walls were similar (116 microns and 109 microns,
      respectively), but much smaller than on occlusal walls (310 microns). Cement
      thicknesses at occlusal locations were significantly thicker in molars than in
      premolars. Poor correlations existed between cement thicknesses on buccal and
      lingual walls (0.26) and between these and the occlusal walls (0.35) implying
      that incomplete seating is strongly related to tilting or oblique seating.
      CONCLUSION: Under clinical conditions where more inherent difficulties exist,
      special measures must be taken to alleviate the consequences of cement fluid
      dynamics.

PMID- 9627890
TI  - The effect of temperature changes on the dimensional stability of polyvinyl
      siloxane and polyether impression materials.
AB  - STATEMENT OF PROBLEM: Dental impressions are commonly mailed to remote dental
      laboratories and can be subjected to extreme temperature changes; however, the
      effects of these temperature changes on the accuracy of elastomeric impression
      materials are unknown. PURPOSE: This study evaluated the dimensional changes of
      polyether and polyvinyl siloxane impression materials as a function of storage
      temperature. MATERIAL AND METHODS: A total of 144 impressions were made of a
      stainless steel die similar to ADA Specification No. 19. Half of the impressions
      were made in perforated custom trays and the other half in solid trays.
      Measurements of the vertical and horizontal lines on the impressions were made at
      10 minutes, 1 hour, 24 hours, and 26 hours, and storage temperatures ranged from
      4 degrees C to 40 degrees C. RESULTS: Changes in storage temperature had a
      statistically significant effect on the dimensional stability of the horizontal
      and vertical lines. However, overall dimensional changes were extremely small.
      CONCLUSIONS: Storing both impression materials at 4 degrees C for 24 hours and
      then allowing the impressions to reach room temperature resulted in a slightly
      expanded impression that partially compensated for the contraction that occurred
      from polymerization shrinkage. Similar results occurred for polyether material
      only, when stored at 40 degrees C.

PMID- 9627891
TI  - A randomized clinical trial comparing the efficacy of mandibular implant
      supported overdentures and conventional dentures in diabetic patients. Part II.
      Comparisons of masticatory performance.
AB  - STATEMENT OF PROBLEM: Convincing evidence is lacking to demonstrate the
      functional superiority of mandibular implant-supported overdentures over
      conventional dentures. PURPOSE: This randomized clinical trial was conducted to
      compare masticatory functional effectiveness of mandibular implant-supported
      overdentures and conventional dentures in diabetic denture wearers with
      clinically acceptable metabolic control. METHODS: A total of 102 edentulous
      diabetic patients, treated with or without insulin, were randomized to receive a
      new maxillary and either a mandibular conventional denture or an implant
      supported overdenture. Treatment was completed in 89 patients, 37 with
      conventional dentures and 52 with Hader bar-clip attachment overdentures
      supported by two IMZ implants. Besides data from medical and dental histories,
      oromaxillofacial examinations, and questionnaires, masticatory tests were
      performed by patients before and at 6 and 24 months after treatment completion.
      Although 78 patients (28 in the conventional, 50 in the overdenture group)
      performed tests at 6 months after treatment, 68 (25 in the conventional, 43 in
      the overdenture) had performance data for both entry and 6-month posttreatment
      intervals. RESULTS: The two treatment groups were highly comparable in terms of
      general characteristics, quality of original dentures, tissue support, and past
      denture experience. No significant differences were found between patients
      treated for diabetes with or without insulin. All four masticatory performance
      scores with original dentures were higher in the conventional denture group than
      the overdenture group. The posttreatment performance scores for the two treatment
      groups became similar because of the higher gains in the overdenture group.
      Patients with low initial performance scores showed greater posttreatment gains
      with both conventional dentures and overdentures. CONCLUSIONS: The implant
      supported overdenture showed no significant advantage over the conventional
      denture for improving the ability to comminute food in this group of diabetic
      patients with higher than average initial functional levels observed for other
      groups of denture wearers in previous studies.

PMID- 9627892
TI  - Restoration of irradiated patients using osseointegrated implants: current
      perspectives.
AB  - STATEMENT OF PROBLEM: The success rates of osseointegrated implants used to
      restore patients who were irradiated for head and neck tumors are influenced by
      radiation-induced changes in the hard and soft tissues. PURPOSE: This article
      examined, by review of the literature, current perspectives on the restoration of
      irradiated patients using osseointegrated implants. RESULTS: In published reports
      that investigated both intraoral and extraoral applications, irradiation
      decreased implant success rates and the amount of reduction was dependent on the
      location within the craniofacial skeleton. The limited number of implants and
      patients in these studies precludes definitive conclusions regarding the efficacy
      of placing implants into irradiated tissues. The implants placed into the
      irradiated anterior mandible have demonstrated an acceptable implant success rate
      of 94% to 100% with a minimal risk of osteoradionecrosis. The efficacy of
      implants in the posterior mandible has not been examined. Implant success rates
      ranged from 69% to 95% in the irradiated maxilla for intraoral applications.
      Extraoral applications demonstrated excellent implant success rates in the
      temporal bone (91% to 100%). The rates in the anterior nasal floor have varied
      from 50% to 100%. The implant success rates in the frontal bone decreased as the
      length of the studies increased (96% to 33%). The long-term efficacy of implants
      in the irradiated frontal bone is poor.

PMID- 9627893
TI  - Periotest method: implant-supported framework fit evaluation in vivo.
AB  - STATEMENT OF PROBLEM: In implant prosthodontics an accurate fit of the framework
      to the supporting implants is paramount. However, microgaps occur, unknown to the
      clinician until complications arise that implicate errors in fit. Therefore
      prosthodontics would welcome a tool or instrument that provides an objective
      evaluation of the fit at the implant prosthodontic interface. PURPOSE: This
      clinical investigation determined whether a correlation existed between the
      laboratory laser measurement of the abutment analog-framework fit and the
      intraoral abutment-framework fit as measured by the Periotest method. MATERIAL
      AND METHODS: Fifteen subjects received implant-supported remote fixed partial
      denture supported by five (11 subjects) or six (4 subjects) implants in the
      mandibular jaw opposed by a complete maxillary denture. Laser videography was
      used to quantify the fit of the framework to its respective master cast with six
      measurements, while the fit of the framework in the mouth was quantified with the
      Periotest method. Data were statistically analyzed with correlation analyses and
      multiple regression. RESULTS: The overall correlation coefficient between the two
      methods was r = 0.51. Regression analysis of variance revealed that the intercept
      of the laser videography measurement was significant (p < or = 0.05). The mean
      Periotest values and standard deviation for the abutment-framework interface were
      negative (-7.3 +/- 1.2). The variance in part for the Periotest values was
      explained by the misfits in the vertical axis (delta Z, +0.471) and in the misfit
      direction of the centroids in the x-y plane (X-YVD, -0.244). CONCLUSION: There
      was no single variable among the six measurement variables that strongly
      correlated with the periotest method in the identification of mistfit at the
      bearing surface as indicated by the Periotest value measurements. The misfit
      laser variables that were weakly correlated to the Periotest values should be
      observable clinically with greater scrutiny.

PMID- 9627894
TI  - Association between dental occlusal variables and intraarticular
      temporomandibular joint disorders: horizontal and vertical overlap.
AB  - STATEMENT OF PROBLEM: It has been suggested that dental occlusion may play a role
      in the development of intraarticular temporomandibular joint disorders. PURPOSE:
      This study evaluated the relationship between horizontal and vertical overlap and
      intraarticular temporomandibular joint disorders. MATERIAL AND METHODS: Vertical
      and horizontal overlap of the anterior teeth of 82 asymptomatic volunteers and
      263 symptomatic patients were examined. RESULTS: Fifty-five (67%) of the
      asymptomatic volunteers had normal joints and 27 (33%) had disk displacement. Two
      hundred and twenty-one patients (84%) had disk displacement and 42 (16%) had
      bilateral symptomatic normal joints. Horizontal overlap equal to or greater than
      4 mm was more prevalent in the symptomatic patient group as compared with the
      asymptomatic volunteer group (p < 0.05). Vertical overlap equal to or greater
      than 4 mm demonstrated no significant differences. CONCLUSION: Horizontal overlap
      equal to or greater than 4 mm was greater in symptomatic patients with
      intraarticular temporomandibular joint disorders.

PMID- 9627895
TI  - Modulation of myofascial pain by the reproductive hormones: a preliminary report.
AB  - STATEMENT OF PROBLEM: The predominance of myofascial pain in women in
      childbearing years suggests that the reproductive hormones may play a role in
      this pain disorder. PURPOSE: The potential influence of these hormones on
      myofascial pain was evaluated. METHODS: Pain patterns were compared across three
      consecutive menstrual cycles in oral contraceptives users (OC group) and nonusers
      (Non-OC group). RESULTS: Preliminary results showed that within menstrual cycle
      variability of daily pain was higher than the nonusers group. In addition to
      their low variation, pain levels of oral contraceptives users remained positive
      across the hormonal cycle, whereas in nonusers, peaks of pain alternated
      frequently with pain-free periods. These data suggest that pain levels in oral
      contraceptives users may be more constant than those of nonusers. CONCLUSIONS:
      This potential hormonal influence on myofascial pain levels among oral
      contraceptives users may represent one of the various adverse effects induced by
      oral contraceptives at the trigeminal area in sensitive subjects. Evidence
      supporting the link between estrogen, nitric oxide, and inflammatory processes is
      presented.

PMID- 9627896
TI  - Crown retention with use of a 5% glutaraldehyde sealer on prepared dentin.
AB  - STATEMENT OF PROBLEM: A previous study showed that a resin sealer decreased
      casting retention with zinc phosphate cement. PURPOSE: This study determined
      whether a nonresin sealer applied to prepared dentin affected the retention of
      cemented castings. MATERIAL AND METHODS: Extracted molars were prepared with a
      flat occlusal, 20-degree taper and 4 mm axial length. The axial surface area of
      each preparation was determined and samples were distributed to achieve
      equivalent groups. Gluma Desensitizer sealer was used to seal the dentin before
      provisionalization and again before crown cementation. An Olympia alloy casting
      was produced for each preparation and cemented with a seating force of 20 Kg with
      either Mizzy's zinc phosphate, Ketac-Cem glass ionomer, or Resinomer material in
      combination with One Step adhesive. Castings were thermocycled, then removed
      along the path of insertion with an Instron testing machine. A two-factor
      analysis of variance was used with alpha = 0.05 and n = 9.10. RESULTS: Mean
      dislodgment stresses for unsealed and sealed conditions were 6.3 and 6.4 MPa for
      zinc phosphate, 9.1 and 10.1 MPa for glass ionomer, and 12.1 and 12.6 MPa for the
      resin cement. The means for the three cements were statistically different (p <
      0.001). The effect of sealer (p = 0.369) and cross product interactions (p =
      0.820) were not significant. CONCLUSIONS: The use of the glutaraldehyde-based
      system as a desensitizing treatment for prepared teeth had no effect on crown
      retention for any of the three cements evaluated and the modified resin cement
      produced the highest mean dislodgment stress that exceeded the strength of the
      tooth.

PMID- 9627897
TI  - Effects of three soldering techniques on the strength of high-palladium alloy
      solder joints.
AB  - STATEMENT OF PROBLEM: Little information is available on the optimum technique
      for soldering high-palladium alloys, which have gained considerable popularity
      for prosthodontic applications. PURPOSE: The objective of this study was to
      compare the flexural stress at the proportional limit of four noble dental alloy
      specimens soldered with torch, oven, and infrared-techniques. MATERIALS AND
      METHODS: The high-palladium alloys studied were Legacy XT (Jelenko), Freedom Plus
      (Jelenko), and IS 85 (Williams/Ivoclar). A gold-palladium alloy, Olympia
      (Jelenko), served as the control. Thirty round bars, 18 x 3 mm, were cast from
      each alloy, cut in half, aligned, and joined using Olympia Pre solder (Jelenko)
      for the gas-oxygen torch and the infrared technique and Alboro LF solder
      (Jelenko) for the oven technique. Each soldered bar was subjected to three-point
      bending, and the maximum elastic stress or strength of the solder joint was
      calculated at the proportional limit. Data were analyzed by two-way ANOVA and the
      Ryan-Einot-Gabriel-Welsch (REGW) multiple range test at the 0.05 level of
      significance. RESULTS: There was no significant difference between torch and oven
      soldering, but both were significantly different from the infrared technique.
      ANOVA showed a significant difference between alloys, but this difference could
      not be detected with the REGW test. SEM examination of the fracture surfaces
      revealed grooves associated with the path of crack propagation. X-ray energy
      dispersive spectroscopic analysis failed to detect copper in the solders, and
      there were no significant changes in the solder compositions after the melting
      procedures. CONCLUSIONS: All three techniques can yield satisfactory solder
      joints in high-palladium alloys. These joints should be well-polished to achieve
      optimal strength.

PMID- 9627898
TI  - The effect of aging and ovariectomy on mandibular condyle in rats.
AB  - STATEMENT OF PROBLEM: It is important for dentists to understand the effect of
      systemic hormonal change on the osseous oral structures. PURPOSE: This study
      examined the effect of aging and ovariectomy on rat mandibular condyle. MATERIAL
      AND METHODS: Seventy-two 120-day-old female Fischer rats were killed at 7, 14,
      30, and 60 days after bilateral ovariectomy or sham surgery. As the baseline
      control group, eight animals were killed on day 0 without surgeries. Changes in
      the bone mineral density and bone marrow area were detected through dual-energy x
      ray absorptiometry and soft x-ray photography, respectively. RESULTS: No
      significant difference of bone mineral density was found between the bilateral
      ovariectomy and sham surgery groups with dual-energy x-ray absorptiometry,
      probably because the thickness of cortical bone obscured any possible changes in
      trabecular bone. Age-related osteosclerotic changes were found in the sham group
      with soft x-ray photography. In contrast, the bilateral ovariectomy group showed
      little change in bone marrow area in relation to time course; on the other hand,
      the value of their bone marrow area became significantly larger than that of the
      sham surgery group from 14 days after ovariectomy onward. CONCLUSIONS: It was
      inferred that estrogen deficiency caused the significantly large marrow area
      found in the rat mandibular condyle. Although much more research is necessary,
      this study allowed us to speculate that osteoporotic changes may occur in the
      mandibular condyle of postmenopausal women.

PMID- 9627899
TI  - Organizational considerations for an electronic curriculum. Part II: A multimedia
      approach to dental education in general and to prosthodontics in particular.
AB  - STATEMENT OF PROBLEM: In using multimedia electronic knowledge-transfer as a tool
      in dental education, an overriding concern has centered on how to devise an
      organizational model that will accommodate the vast and diverse arrays of
      information involved, yet be sufficiently simple to provide students with a
      rational and consistent means of accessing the information they require. PURPOSE:
      This article presents a model that adopts the Natural History of Dental Diseases
      as the organizing principle. This article also encourages a mindset in
      prosthodontics that focuses on the dynamics of energy-dispersal through the
      supporting structures, in an attempt to provide learners with a deeper cognitive
      dimension for problem solving and to facilitate their empowerment as life-long
      learners.

PMID- 9627900
TI  - Long-term reinforced fixed provisional restorations.
AB  - Extensive prosthodontic treatment often requires fabrication of long-term
      provisional restorations. Numerous materials and techniques have been described
      for prolonged insertion of interim restorations. This article describes a
      procedure for fabrication of long-term reinforced heat-processed provisional
      restorations based on a diagnostic wax-up. Reinforced heat-processed provisional
      restorations reduced flexure, which minimizes progressive loss of cement and
      diminished the possibility of recurrent decay. Occlusal stability and vertical
      dimension were maintained because of greater wear resistance. Occlusion, tooth
      contours, and pontic design developed in the provisional restoration were
      duplicated in the definitive restoration. The use of a matrix from a diagnostic
      wax-up facilitated fabrication of the prosthesis, and made the procedure less
      time-consuming and more predictable.

PMID- 9627901
TI  - Esthetic considerations in restoring endodontically treated teeth with posts and
      cores.
AB  - Posts and cores are often required for the restoration of endodontically treated
      teeth. Many methods for making post-and-core reconstructions have been described.
      With the increased use of all-ceramic systems for esthetic tooth restorations,
      there is a need for esthetic core reconstructions. This article describes several
      methods for fabricating esthetic posts and cores.

PMID- 9627902
TI  - Cost-saving implant training aids.
AB  - This article describes a simple step-by-step procedure that uses inexpensive
      materials to enable those who wish to learn procedures used in the construction
      of a screw-type implant overdenture to practice these procedures before they use
      expensive precious metal components. The use of this procedure will result in
      considerable savings in training costs and affords a greater opportunity to
      provide practical experience before making this type of an overdenture for
      patients. It could also provide for a rapid expansion in the number of trained
      personnel who could make this form of treatment available to a larger number of
      patients.

PMID- 9627903
TI  - Vacuum-formed matrix as a guide for the fabrication of craniofacial implant
      tissue bar-retained auricular prostheses.
AB  - Craniofacial implant-retained auricular prostheses usually require a tissue bar
      and/or retentive elements in addition to the prosthetic ear. Complete coverage of
      the tissue bar and retentive elements in a given bulk of prosthetic material is
      sometimes difficult to achieve, but it is crucial to ensure that all the
      prosthetic components are kept within the contour of the auricular prosthesis to
      maintain esthetics and form. This article describes a method for fabrication of
      auricular prostheses with all the elements predictably confined within the
      anatomic contour of the prostheses.

PMID- 9627904
TI  - Carnitine as an ergogenic aid in health and disease.

PMID- 9627905
TI  - Does creatine supplementation enhance athletic performance?

PMID- 9627906
TI  - The role of carnitine and carnitine supplementation during exercise in man and in
      individuals with special needs.
AB  - Carnitine is critical for normal skeletal muscle bioenergetics. Carnitine has a
      dual role as it is required for long-chain fatty acid oxidation, and also
      shuttles accumulated acyl groups out of the mitochondria. Muscle requires
      optimization of both of these metabolic processes during peak exercise
      performance. Theoretically, carnitine availability may become limiting for either
      fatty acid oxidation or the removal of acyl-CoAs during exercise. Despite the
      theoretical basis for carnitine supplementation in otherwise healthy persons to
      improve exercise performance, clinical data have not demonstrated consistent
      benefits of carnitine administration. Additionally, most of the anticipated
      metabolic effects of carnitine supplementation have not been observed in healthy
      persons. The failure to demonstrate clinical efficacy of carnitine may reflect
      the complex pharmacokinetics and pharmacodynamics of carnitine supplementation,
      the challenges of clinical trial design for performance endpoints, or the
      adequacy of endogenous carnitine content to meet even extreme metabolic demands
      in the healthy state. In patients with end stage renal disease there is evidence
      of impaired cellular metabolism, the accumulation of metabolic intermediates and
      increased carnitine demands to support acylcarnitine production. Years of
      nutritional changes and dialysis therapy may also lower skeletal muscle carnitine
      content in these patients. Preliminary data have demonstrated beneficial effects
      of carnitine supplementation to improve muscle function and exercise capacity in
      these patients. Peripheral arterial disease (PAD) is also associated with altered
      muscle metabolic function and endogenous acylcarnitine accumulation. Therapy with
      either carnitine or propionylcarnitine has been shown to increase claudication
      limited exercise capacity in patients with PAD. Further clinical research is
      needed to define the optimal use of carnitine and acylcarnitines as therapeutic
      modalities to improve exercise performance in disease states, and any potential
      benefit in healthy individuals.

PMID- 9627907
TI  - Creatine supplementation and exercise performance: an update.
AB  - Creatine, a natural nutrient found in animal foods, is alleged to be an effective
      nutritional ergogenic aid to enhance sport or exercise performance. Research
      suggests that oral creatine monohydrate supplementation may increase total muscle
      creatine [TCr], including both free creatine [FCr] and phosphocreatine [PCr].
      Some, but not all, studies suggest that creatine supplementation may enhance
      performance in high-intensity, short-term exercise tasks that are dependent
      primarily on PCr (i.e., < 30 seconds), particularly laboratory tests involving
      repeated exercise bouts with limited recovery time between repetitions;
      additional corroborative research is needed regarding its ergogenic potential in
      actual field exercise performance tasks dependent on PCr. Creatine
      supplementation has not consistently been shown to enhance performance in
      exercise tasks dependent on anaerobic glycolysis, but additional laboratory and
      field research is merited. Additionally, creatine supplementation has not been
      shown to enhance performance in exercise tasks dependent on aerobic glycolysis,
      but additional research is warranted, particularly on the effect of chronic
      supplementation as an aid to training for improvement in competitive performance.
      Short-term creatine supplementation appears to increase body mass in males,
      although the initial increase is most likely water. Chronic creatine
      supplementation, in conjunction with physical training involving resistance
      exercise, may increase lean body mass. However, confirmatory research data are
      needed. Creatine supplementation up to 8 weeks has not been associated with major
      health risks, but the safety of more prolonged creatine supplementation has not
      been established. Creatine is currently legal and its use by athletes is not
      construed as doping.

PMID- 9627908
TI  - Cobalamin (vitamin B12) and holotranscobalamin changes in plasma and liver tissue
      in alcoholics with liver disease.
AB  - OBJECTIVE: We wanted to know if alterations in plasma cobalamin (B12)
      concentration and B12 carriers, e.g., holotranscobalamins (holo TC), occur in
      blood and liver tissue from patients with severe alcoholic liver disease. Our
      purpose was to test the hypothesis that liver disease may disrupt B12
      distribution. METHOD: Total B12, as well as B12 bound to transcobalamin I, II,
      III (holo TC), were measured to determine their concentration in plasma and in
      liver tissue; Poteriochromonas malhamensis--a protozoan reagent served to measure
      only metabolically active (true) B12. Total B12 as distributed in holo TC in
      plasma and liver tissue of healthy subjects (controls) were compared to patients
      with severe alcoholic liver disease. RESULTS: Severe liver disease initiates
      highly elevated B12 levels in plasma and a lowered liver tissue total B12
      concentration. The percent of B12 distributed to holo TC II is significantly
      depleted during liver disease. In contrast, holo TC I and III are elevated in
      plasma during liver disease and contain more B12 than controls. Total B12 and B12
      distributed to TC are lower in diseased liver tissue. CONCLUSION: Severe
      alcoholic liver disease involves leakage of total B12 from liver tissue into the
      plasma. Holo TC I and III concentration increases in plasma; this preserves the
      high plasma B12 from being excreted. However, plasma holo TC II B12 distribution
      is decreased, indicating that there is a depression of exogenous B12 entering the
      plasma and tissues. In severe liver disease, liver tissue B12 binding and storage
      by TC is disrupted and causes B12 to leak out of the liver into the circulation.
      Eventually liver disease could produce enough severe tissue B12 deficits to cause
      metabolic dysfunction despite elevated plasma total B12. Elevation of plasma B12,
      accompanied by a lowering of holo TC II distribution, seemed to be a useful index
      of liver disease severity suggesting preventive treatment.

PMID- 9627909
TI  - Anxiety and adipose essential fatty acid precursors for prostaglandin E1 and E2.
AB  - OBJECTIVE: The purpose of the present study was to investigate the relation state
      and trait anxiety and adipose tissue essential fatty acid precursors for
      prostaglandins E1 and E2. METHODS: The sample consisted of 144 male and female
      Cretan adults, 23 to 69 years of age. Anthropometric and arterial blood pressure
      measurements were taken, and adipose tissue samples as well as data concerning
      general health habits were collected. Dietary data were collected using the
      weekly food frequency questionnaire and the 24-hour dietary recall method, while
      state and trait anxiety was assessed through the use of the Spielberger State
      Trait Anxiety Inventory (STAI) and the Zung anxiety scale. RESULTS: State anxiety
      (STAI) related positively with sex (p < 0.0003) and negatively with adipose fat
      myristic acid (C14:0) (p < 0.004). Similarly, Zung trait anxiety related
      positively with sex (p < 0.0001) and negatively with adipose tissue myristic acid
      (C14:0) (p < 0.04). Spielberger trait anxiety related positively with adipose (LA
      + ALA)/(AA + EPA) ratio (p < 0.0002) and negatively with (C14:0) (p < 0.02) and
      dietary monounsaturated fat (p < 0.03). CONCLUSION: It appears that the positive
      relation between trait anxiety and adipose (LA + ALA)/(AA + EPA) ratio may stem
      from the inhibiting role of catecholamines on delta 6 and delta 5 desaturases.

PMID- 9627910
TI  - Effects of supplementation with a combination of antioxidant vitamins and trace
      elements, at nutritional doses, on biochemical indicators and markers of the
      antioxidant system in adult subjects.
AB  - OBJECTIVE: To test the impact of supplementation with nutritional doses of
      antioxidant nutrients on biochemical indicators of vitamin and trace element
      levels. DESIGN: A randomized double-blind trial was performed comparing two
      groups receiving daily either a combination of vitamins (beta-carotene, 6 mg;
      vitamin C, 120 mg; and vitamin E, 30 mg) and trace elements (zinc, 20 mg; and
      selenium, 100 micrograms); or a placebo. SUBJECTS: 401 subjects (166 males aged
      45 to 60 years and 235 females aged to 35 to 60 years). MEASURE OF OUTCOME:
      Biological markers of vitamin and trace element status and free radical
      parameters were measured initially, 3 months, and 6 months after supplemention.
      RESULTS: Mean serum concentrations of alpha-tocopherol, vitamin C, beta-carotene,
      zinc and selenium increased significantly after 3 months of supplementation in
      the group receiving multivitamins associated with minerals. At baseline, 18.2% of
      the men and 5.1% of the women had low concentrations of serum vitamin C (< 20
      mumol/l): 2.4% of the men and 17% of the women presented low concentrations of
      serum retinol (< 1.4 mumol/l): 18.7% of men and 10% of women had serum beta
      carotene < 0.30 mumol/l. None of the study subjects had serum alpha-tocopherol
      concentrations below the limit cut-off point (< 9.3 mumol/l). Low serum zinc
      concentrations (< 10.7 mumol/l) were found in 15.1% of men and 23.8% of women.
      Low serum selenium concentrations (< 0.75 mumol/l) were found in 6% of men and
      6.4% of women. A significant increase in plasma and red cell GPx activity was
      observed in groups receiving supplementation. No modifications were observed
      after 6 months of supplementation for malondyaldehyde. CONCLUSION: This study
      demonstrates the efficacy of an intake of antioxidant vitamins and trace
      elements, given at nutritional doses, on biochemical indicators of vitamin and
      trace elements status.

PMID- 9627911
TI  - Relation of serum ascorbic acid to serum lipids and lipoproteins in US adults.
AB  - OBJECTIVE: To examine the relation of serum ascorbic acid level to serum lipid
      and lipoprotein levels among a random sample of the US adult population. METHODS:
      Using linear regression, the relation of serum ascorbic acid level to serum lipid
      and lipoprotein levels was examined among 5,412 women and 5,116 men enrolled in
      the Second National Health and Nutrition Examination Survey (NHANES II), 1976
      1980. Age, race, body mass index, level of physical activity, level of education,
      alcohol intake, and dietary energy, cholesterol, and fat intakes, and other
      potential confounders were included in the multivariate models. RESULTS: Serum
      ascorbic acid level was independently associated with high-density lipoprotein
      cholesterol (HDL-C) among women; each 1 mg/dl increase in serum ascorbic acid
      level (range 0.1 to 2.7 mg/dl) was associated with a 2 mg/dl increase in HDL-C
      level (p = 0.001). Because other investigators have demonstrated an inverse
      relation between ascorbic acid intake or blood levels and total serum cholesterol
      in individuals with elevated total serum cholesterol levels, we analyzed four
      subgroups of NHANES II participants with total serum cholesterol levels > 200
      mg/dl. Among women with total serum cholesterol levels > or = 200 mg/dl, each 1
      mg/dl increase in serum ascorbic acid level was independently associated with an
      increase of 2 to 3 mg/dl in HDL-C level (p < or = 0.05). Serum ascorbic acid
      level was not significantly associated with other serum lipids or lipoproteins.
      CONCLUSIONS: If the observed associations are linked causally, they would suggest
      that ascorbic acid is a factor in cholesterol homeostasis among women and may be
      particularly important for women at increased risk for coronary heart disease.

PMID- 9627912
TI  - Implications of the weaning pattern on macronutrient intake, food volume and
      energy density in non-breastfed infants during the first year of life.
AB  - OBJECTIVES: To evaluate the implications of the patterns of weaning on the intake
      of macronutrients, energy intake, food volume and the energy density in healthy
      infants in the Mediterranean area of Spain. SUBJECTS AND STUDY DESIGN: Cross
      sectional study of 120 clinically-healthy, non-breastfed infants at the ages of
      4, 6, 9 and 12 months randomly recruited from three pediatric out-patient
      clinics. Nutrition data were obtained from the infant's food preparer using the
      24-hour dietary recall method. RESULTS: Energy intake/kg body weight was within
      the recommended daily allowance and did not vary significantly with age (423
      kJ/kg body weight at 4 months and 443.7 kJ/kg at 12 months). There was a
      progressive decrease in the intake volume (p < 0.001) in which carbohydrate-rich
      foodstuffs were the major factors, and an increase in the energy density (p <
      0.001) in which the protein-rich items were the principal contributors. Lipid
      intake diminished progressively (p < 0.01) to a nadir of 26.4% of energy intake
      at 9 months of age. In each of the meals there was a tendency towards a
      progressive increase in energy intake with age. This increase was achieved by a
      significant increase in energy density (p < 0.001 in all meals, except dinner p <
      0.05). Conversely, the intake volume of breakfast, lunch and dinner remained
      essentially unchanged between 6 and 12 months while that of the mid-evening meal
      decreased markedly. CONCLUSION: Increased energy requirements for growth is
      achieved, mainly, by an increase in the energy density rather than the intake
      volume during food-item diversification in the non-breastfed infant. Cereals were
      the central food item in the weaning diet in our study sample and which
      adequately compensates, in terms of energy requirement, for the early reliance on
      the lipids contained in milk.

PMID- 9627913
TI  - Prospective assessment of coronary heart disease risk factors: the NHANES I
      epidemiologic follow-up study (NHEFS) 16-year follow-up.
AB  - OBJECTIVE: Our specific aim in the 16 year prospective NHANES I epidemiologic
      follow-up study (NHEFS) was to assess the important roles of modifiable dietary
      and behavioral factors in causation and prevention of deaths and hospitalizations
      for coronary heart disease (CHD). METHODS: Using NHEFS 16 year follow-up data
      (1971 to 1987), we studied 5811 subjects, 1958 with and 3853 without CHD events,
      using logistic regression. RESULTS: In age groups 40 to 49, 50 to 59, 60 to 69,
      and 70 to 74 years (at study entry in 1971-4), the numbers of men and women were
      respectively 597 and 1019, 570 and 619, 932 and 1042, and 486 and 546. The
      following factors were independently positively associated (p < .05) with CHD:
      age, serum cholesterol, body mass index, cigarette use, and region (Midwest,
      Northeast). The following factors were independently negatively associated (p <
      .05) with CHD: gender (female), race (black), fish intake, alcohol, high school
      education, moderate exercise, and moderate and heavy habitual physical activity.
      Subjects with serum cholesterol > 249 mg/dl benefitted less (p = .04) from fish
      intake than those with 209 to 249 or < 209, and benefitted less (p = .03) from
      alcohol intake (CHD incidence [%]): [see text] CONCLUSIONS: These associations
      emphasize the important role of modifiable dietary and behavioral factors in the
      causation and prevention of CHD.

PMID- 9627914
TI  - Zinc may regulate serum leptin concentrations in humans.
AB  - OBJECTIVE: Leptin, the product of the ob gene, plays a key role in a feedback
      loop that maintains energy balance by signaling the state of energy stores to the
      brain and by influencing the regulation of appetite and energy metabolism. Zinc
      also plays an important role in appetite regulation. Thus, we evaluated the
      relationship between zinc status and the leptin system in humans. METHODS: We
      studied nine healthy men with marginal zinc deficiency, induced by dietary means,
      before and after zinc supplementation. RESULTS: Zinc restriction decreased leptin
      levels while zinc supplementation of zinc-depleted subjects increased circulating
      leptin levels. In addition, zinc supplementation increased IL-2 and TNF-alpha
      production that could be responsible for the observed increase in leptin
      concentrations. CONCLUSIONS: Zinc may influence serum leptin levels, possibly by
      increasing the production of IL-2 and TNF-alpha.

PMID- 9627915
TI  - Effects of exogenous recombinant human growth hormone on an animal model of
      suboptimal nutrition.
AB  - BACKGROUND: Nutritional dwarfing, a form of suboptimal nutrition, has been
      identified as a frequent cause of short stature and delayed sexual development in
      children. Retarded growth is an adaptive response to suboptimal nutrition.
      OBJECTIVE: To assess whether recombinant human growth hormone (rhGH) may promote
      growth during various levels of suboptimal nutrition. METHODS: Using a previously
      developed rat model of suboptimal nutrition, six groups of rats (six rats/group)
      were fed a balanced 1:1 carbohydrate:fat ratio diet for 4 weeks. Three of the
      groups were administered daily injections of rhGH (0.1 mg/100 g BW)
      subcutaneously in the back while the other three groups were kept as controls and
      were given similar dosages of normal saline solution (NSS). Restricted rats
      within each treatment group were pair fed 80 and 60% of the ad-libitum rats
      intake. Daily intake of the 80 and 60% fed groups were determined based on the
      intake of the ad-libitum fed groups. Serum IGF-I and insulin were determined
      after 4 weeks of dietary treatment by radioimmunoassay while IGFBP-3 was
      determined by an immunoradiometric assay. Body composition was assessed in all
      rats by carcass analysis. RESULTS: After 4 weeks, total weight gain and tail
      growth were higher (p < 0.05) in the rhGH treated group at 80 and 60% of-libitum
      energy intake. Serum levels of IGF-I and IGFBP-3 were higher (p < 0.05) in rhGH
      treated rats fed at 60% of ad-libitum. In comparison to the NSS groups,
      administration of rhGH in rats fed ad-libitum increased total body water. Energy
      restriction caused decreased fat percentage (p < 0.05) in both rhGH and NSS
      groups without differences among treated groups. CONCLUSION: These results
      suggest that the anabolic effects of rhGH may overcome mild to moderate energy
      restriction.

PMID- 9627916
TI  - The association of oral contraceptive use with plasma 25-hydroxyvitamin D levels.
AB  - OBJECTIVE: This analysis was conducted to compare wintertime 25-hydroxyvitamin D
      (25OHD) levels of young women who did and did not use oral contraceptives (OC).
      METHODS: The subjects were 66 Caucasian women aged 20 through 40 recruited from
      the Boston area. Plasma 25OHD was measured in February or March and again 1 year
      later. Other measurements included height, weight and vitamin D intake from diet
      and supplements. RESULTS: The initial mean 25OHD level of the 26 OC users was 41%
      higher than those of nonusers before adjustment for age and vitamin D intake (83
      +/- 40 (sd) nmol/L compared with 59 +/- 22), and 39% higher after adjustment (p =
      0.003). Five women who discontinued OC use during the year following their
      initial measurement all had decreases in their 25OHD levels (mean change was 
      25.5 +/- 17.7 (SD) nmol/L), whereas levels in women whose OC use or non-use was
      constant did not change. CONCLUSION: OC use increases circulating levels of
      25OHD, and should be considered when interpreting values obtained for clinical
      evaluation or nutrition research.

PMID- 9627917
TI  - Nuts and plasma lipids: an almond-based diet lowers LDL-C while preserving HDL-C.
AB  - OBJECTIVE: To compare lipid-altering effects of an almond-based diet with an
      olive oil-based diet, against a cheese and butter-based control diet. METHODS:
      Forty-five free-living hyperlipidemic men (n = 12) and women (n = 33) with a mean
      plasma total cholesterol (TC) of 251 +/- 30 mg/dL followed one of three diets;
      almond-based, olive oil-based, or dairy-based for 4 weeks. Total fat in each diet
      was matched, and the study-provided sources of fat comprised the major portion of
      fat intake. RESULTS: Reductions in TC and low-density lipoprotein-cholesterol
      (LDL-C) between the three groups were significantly different from the almond
      group (both p < 0.001). Within group analysis revealed that the almond-based diet
      induced significant reductions in TC (p < 0.05), LDL-C (p < 0.001), and the
      TC:HDL ratio (p < 0.001), while HDL-C levels were preserved. TC and HDL-C in the
      control diet were significantly increased from baseline (both p < 0.05), while
      the olive oil-based diet resulted in no significant changes over the study
      period. Weight did not change significantly. CONCLUSION: Results suggest that the
      more favorable lipid-altering effects induced by the almond group may be due to
      interactive or additive effects of the numerous bioactive constituents found in
      almonds.

PMID- 9627918
TI  - Zinc status relates to hematological deficits in middle-aged women.
AB  - OBJECTIVE: The objective of our study was to investigate zinc (Zn) status and the
      effects of Zn supplementation in relation to iron deficiency anemia in middle
      aged women. It is important to define the role of Zn in hematologic abnormalities
      and to determine the frequency of Zn deficiency. METHODS: Fifty-two Japanese
      women, selected from a health examination survey on 6200 women, had hemoglobin
      concentrations below 12.0 g/dl, total iron binding capacity (TIBC) below 390
      micrograms/dl and fairly normocytemia. These 52 were divided into three groups
      and we then compared the hematological status before and after iron (group A) or
      Zn (group B) or iron plus Zn (group C) supplementation. RESULTS: After treatment,
      concentrations of hemoglobin (Hb) increased slightly in groups A and B, but not
      statistically significant. In group C, Hb levels were significantly increased
      from 10.8 +/- 1.1 to 12.8 +/- 1.1 g/dl. Furthermore, numbers of RBC and
      reticulocytes, and concentrations of albumin were also increased significantly.
      Increased values over 1.0 g/dl of hemoglobin levels were noted in four women
      (26.6%) in group A, three women (14.2%) in group B and 13 women (81.2%) in group
      C. CONCLUSION: Zn status to some extent can account for hematological
      abnormalities in middle-aged women. At least 5.0% of middle-aged Japanese women
      may have Zn deficiency. Normocytic anemia with low TIBC levels may serve as a
      good indicator of a marginal Zn deficiency.

PMID- 9627919
TI  - Fibromyalgia--a hidden link?

PMID- 9627920
TI  - Objectified selves: an analysis of medicines in Andean sacrificial healing.
AB  - This analysis of medicines used in a Quechua soul-calling ritual in the southern
      Peruvian Andes demonstrates that the items in sacrificial bundles (despachos)
      embody the identity of patients. The manipulation of these medicinal objects
      gives insight into the meaning of the concept of embodiment in the Andean
      cultural context and expands Western conceptions of embodiment. An examination of
      the material representation of the body, the sacrificial object, illuminates the
      components of embodied identity in this particular cultural context. Analysis of
      the manipulation of medicines further illuminates the potency and efficacy of
      symbolic healing to transform the phenomenological world of the patient.

PMID- 9627921
TI  - Hospital trash: cleaners speak of their role in disease prevention.
AB  - Feminist researchers have contrasted the caring provided by women in hospitals
      with a more fragmented "curing" approach, which they identify with the
      predominantly male professions of medicine and surgery. The author spoke with
      hospital cleaners about their jobs and their health. Several themes emerged: the
      invisibility of the cleaning function, lack of respect for cleaners,
      representations of cleaning as undemanding, and assumptions that women's work in
      cleaning is particularly easy. Cleaners use various strategies to combat these
      stereotypes but receive little help from administrators or fellow employees.
      There is a hierarchy in the status of Quebec hospital workers with curing
      (doctors) at the top, followed by caring and healing (nurses, therapists, and
      attendants), and hygiene (cleaners, sterilizers, and launderers) at the bottom.
      Authority hierarchies in health care are not related to gender in a simple way,
      although there is discrimination against women cleaners. The fact that cleaning,
      especially cleaning performed by women, is invisible to managers, other hospital
      personnel, and patients has important consequences for cleaners' and for
      patients' health.

PMID- 9627922
TI  - Home care and prevention.
AB  - This article focuses on the practices and conceptions of prevention in home care
      that were prevalent among Quebec families during the first half of the 20th
      century. The analysis is based on an examination of 585 recipes in which
      prevention was an objective. The analysis finds that there are three prevention
      purposes in home care: strengthening, which includes caregiving acts that
      maintain good health and fortify the whole or particular parts of the body;
      cleansing and purifying, which include any care aimed at eliminating accumulated
      substances from the body; and finally, warding off illness. The discussion
      insists on the holistic nature of these practices and on their relationship to
      women's work.

PMID- 9627923
TI  - Science, nature, and tradition: the mass-marketing of natural medicine in urban
      Ecuador.
AB  - In the past 15 years, "natural" medicine has become increasingly popular in the
      southern Ecuadoran city of Cuenca. Natural medicine products, which are distinct
      from traditional herbal remedies, are commercially packaged and processed and
      sold in a number of retail outlets in the central shopping district. This article
      discusses the results of field research to determine the client base of natural
      medicine and the reasons for its growing popularity among the poorer classes in
      Ecuador. Using an interpretative framework that posits that medical products
      carry symbolic messages, I discuss the ways in which important themes of modern
      life in Ecuador are played out in the packaging and marketing of these products.
      This research supports the growing body of literature that argues against a
      medical-systems approach to analyzing medical plurality by highlighting the
      multiple ideologies found in Ecuadoran beliefs about commercial natural medicine.

PMID- 9627924
TI  - Globality and constructions of world health.
AB  - Explorations of the social construction of health and illness reveal that popular
      and professional discourses on health and disease implicitly contain underlying
      images of how societies can or should be structured. Globality, which is a notion
      that refers to the consciousness of the world as a single place, suggests that
      these images of world structure are now salient. This article describes four
      current discourses of "work health" and discusses them in terms of their
      underlying ideal images of world order. The four images of the world are defined
      in terms of four elemental points of reference: individuals, societies, the
      system of societies, and humankind. These ideal images have either a gemeinschaft
      (community) or gesellschaft (society) orientation. An anthropology of globality
      can refine and extend our understandings of discourses of world health.
      Sensitivity to these discourses and their world-oriented ideological roots should
      help to demystify the notion of world health.

PMID- 9627925
TI  - Caida de mollera among children of Mexican migrant workers: implications for the
      study of folk illnesses.
AB  - Information about the folk illness caida de mollera was collected from Mexican
      and Mexican American migrant mothers who had treated their children for the
      illness, and from physicians in a clinic that served this population. These
      physicians believed that the vast majority of the sets of symptoms were worthy of
      medical attention and could be life threatening if not treated. This research
      report concurs with other studies that suggest that although Mexican folk
      illnesses are conceptualized to have folk-social and psychological causes, they
      are also seen to have biological causes and physiological symptoms that can be
      treated by biomedical methods. This report outlines a model for understanding
      aspects of folk illnesses that includes folk vs. biomedical ideas about disease,
      causes vs. symptoms, and psychological vs. physiological aspects of sickness. It
      also suggests that the kinds of questions anthropologists ask about these
      illnesses may need to be modified--shifting away from questions about treatments
      of causes and refocusing on those about the treatment of physiological symptoms-
      if we are to more fully understand home approaches to the management of these
      illnesses.

PMID- 9627926
TI  - Characteristics of violent versus nonviolent patients with schizophrenia.
AB  - Recent research has demonstrated an associative link between some forms of mental
      illness and violence. While much of this violence is committed by persons with
      schizophrenia, the characteristics of violent versus nonviolent schizophrenic
      patients has received limited attention. Two studies with small sample sizes
      compared these groups on psychological dimensions in acute care settings, but
      there appears to be no study of continuing care inpatients. This study compared a
      statewide sample of violent and nonviolent inpatients with schizophrenia on
      several domains of social interpersonal behavior. In a between-group analysis,
      violent patients showed evidence of serious dysfunction in community self-care
      and community adjustment, whereas the nonviolent were more impaired in the areas
      of depression, restlessness, and internal confusion. A within-group analysis of
      patients with interpersonal violence and those with noninterpersonal violence
      yielded similar findings of serious community dysfunction versus internal
      confusion. The implications are discussed.

PMID- 9627927
TI  - Behavioral treatment of attentional dysfunction in chronic, treatment-refractory
      schizophrenia.
AB  - Attentional impairment is both a core characteristic of schizophrenia and a
      factor in producing poor outcomes in rehabilitative treatment. While cognitive
      rehabilitation interventions have demonstrated some success, the severity of some
      patients' attentional impairment is such that they cannot attend to material in
      these treatments, leading to unsatisfactory outcomes. In this paper, we report on
      the results of a behavioral intervention designed to increase attention span in
      the lowest functioning group of schizophrenia patients on a long-term inpatient
      unit. The treatment is based on social-learning procedures, especially the
      principle of shaping. Results indicate that chronic, treatment refractory
      patients with severe attentional impairment, including those with IQs near or
      within the mentally retarded range, can improve their attention spans to over 45
      minutes with this treatment.

PMID- 9627928
TI  - Training in community psychiatry: new opportunities.
AB  - The authors describe the impact on training that accompanied an assignment of
      senior (PGY-4) residents to work one-half day each week for a six month period at
      a community-based agency concerned with the care of persons with severe and
      persistent mental illness who were formerly homeless. As the goals and methods of
      psychiatric training are rethought and adapt to programmatic shifts and economic
      pressures, new opportunities open up to move treatment and training to the "front
      lines" in the community where an innovative therapeutic armamentarium for persons
      with severe and chronic mental illness is developing.

PMID- 9627929
TI  - Black and white patients response to antidepressant treatment for major
      depression.
AB  - Differences in response to psychopharmacologic agents according to race has so
      far primarily focused on investigations related to the response of Asian-American
      patients to neuroleptics and lithium. In this article, we present evidence which
      depicts that black patients need lower doses of tricyclic antidepressants (TCAs)
      than white patients to attain a similar response in the treatment of major
      depression. Likewise, we also advance that black patients might need lower doses
      of selective serotonin re-uptake inhibitor antidepressants (SSRIs) than white
      patients to attain a similar response in the treatment of major depression.
      Further studies are suggested to confirm these findings.

PMID- 9627931
TI  - The Assaulted Staff Action Program (ASAP): common issues in fielding a team.
AB  - Thirty-five years of empirical research have continuously documented the
      potential negative impact of patient assaults on staff. The Assaulted Staff
      Action Program (ASAP) is a voluntary, peer-help, systems-wide crisis intervention
      debriefing approach for employee victims of these assaults. ASAP has been
      associated with providing needed clinical support for victims, declines in
      violence, and cost-effectiveness in service delivery. A previous paper outlined
      the basic steps needed to field and ASAP team. This paper continues to address
      this need by outlining the most commonly encountered ASAP problems and solutions
      that have evolved in the first eight years of ASAP programs. The implications are
      discussed.

PMID- 9627930
TI  - An update on the impact of gun control legislation on suicide.
AB  - OBJECTIVE: The authors review recent literature examining the impact of gun
      control legislation on suicide rates. METHOD: MEDLINE and PsychLIT searches on
      gun ownership, gun control, and psychiatric firearm-related topics from 1982
      through March 1997 were examined for reports focusing on gun control legislation
      and suicide. RESULTS: Suicide rates typically decreased following implementation
      of a variety of firearm control laws. Suicide-prone individuals seldom substitute
      other means or go outside legal channels for suicide weapons. Firearm
      restrictions may decrease the ready accessibility of firearms enough to allow the
      peak period of suicidality to pass. CONCLUSION: The findings support gun control
      measures as a strategy for reducing suicide rates.

PMID- 9627933
TI  - Immunization with a plasmid DNA containing the gene of trans-sialidase reduces
      Trypanosoma cruzi infection in mice.
AB  - Trypanosoma cruzi, the protozoan parasite that causes Chagas' disease, does not
      synthesize sialic acid, but expresses a trans-sialidase that catalyses the
      transfer of sialic acid from host glycoconjugates to the parasite surface.
      Several lines of evidence suggest that this enzyme is a virulence factor
      implicated in the establishment of infection. Here we studied whether
      immunization with a plasmid DNA containing a gene encoding for the catalytic
      domain of the enzyme could elicit protective immunity against T. cruzi infection
      in mice. We observed that immunization with this plasmid DNA generated antibody
      and T-cell mediated immune responses. Antibodies recognized the native enzyme and
      inhibited its activity in vitro. Upon challenge with bloodstream trypomastigotes,
      immunized animals displayed reduced parasitemia and mortality.

PMID- 9627932
TI  - Comparison of the immunological and protective responses elicited by
      microencapsulated formulations of the F1 antigen from Yersinia pestis.
AB  - Purified native F1 antigen from Yersinia pestis was used to assess controlled
      release vaccine delivery systems in poly(lactide-co-glycolide) (PLG)
      microparticles and liposomes. Antigen encapsulated in PLG microparticles induced
      high serum titres when injected i.p. in mice: mucosal IgA was also detected. Mice
      immunized with F1 in Alhydrogel or PLGs were protected against subcutaneous
      challenge with Y. pestis. F1 antigen surface-labelled onto liposome vesicles
      stimulated high serum titres in Balb/c mice and also induced a mucosal response:
      F1-labelled liposomes protected mice against challenge with up to 1 x 10(5)
      organisms. These findings indicate that a significant immune response is induced
      by immunizing with F1 formulated in PLGs and liposomes and that protection was
      achieved after only one dose.

PMID- 9627934
TI  - Ad hoc survey of hepatitis B vaccination campaign in newborns of HBsAg positive
      mothers and in 12-year-old subjects in southern Italy.
AB  - The ongoing vaccination campaign against hepatitis B (HB) for newborns of
      hepatitis B surface antigen (HBsAg) positive mothers and for 12-year-old subjects
      was evaluated in Naples, Italy, an area of relatively high HB endemicity.
      Subjects were recruited by a random sampling procedure. Among 2060 pregnant women
      studied, 1887 (91.6%) were screened for HBsAg. HBsAg prevalence was 2.5%
      (47/1887). Immunoprophylaxis according to the protocol (immunoglobulins within 24
      h plus vaccine within 7 days after birth) was administered in 26 (55.3%) out of
      the 47 newborns of HBsAg positive mothers; vaccination was delayed (later than 7
      days after birth) for 14 (29.8%) infants; in the remaining seven newborns (14.9%)
      were not given immunoglobulins at birth. All infants were vaccinated. Out of the
      1000 adolescents sampled 130 (13%) were not found due to an inaccurate census
      list; 727 (83.3%) of the 870 investigated had received a three-dose HB vaccine
      series. Overall, the HB vaccination program in Italy is working well. However,
      further efforts should be made to improve the efficacy and effectiveness of the
      campaign.

PMID- 9627935
TI  - A simplified vaccinologists' vaccinology and the pursuit of a vaccine against
      AIDS.
AB  - Vaccinology is the science and engineering of developing vaccines to prevent
      infectious diseases. Guidelines come from knowledge of pathogenesis and from
      successful past vaccines. The vaccine enterprise relies on the evolution of
      appropriate science and technology. Governmental support and industrial
      participation are key to successful development of new vaccines. A large
      challenge for vaccinology is a vaccine which protects against AIDS. Though
      misguided in its first decade, current vaccine research is directed to use of any
      and all viral antigens and to elicit both cell-mediated and humoral immune
      responses that are resident, with memory, at the mucosal sites of viral entry.
      Recent seminal discoveries guiding the future include selective elicitation of
      both Type 1 and Type 2 immune responses, and prime-boosting using recombinant
      viral or DNA vectors and expressed antigens. Success in vaccinology depends on
      simplification of the complex and on iterative processes in a well-defined
      pathway. The present and future of vaccinology are discussed in depth.

PMID- 9627936
TI  - Modelling the incidence of measles in Canada: an assessment of the options for
      vaccination policy.
AB  - A range of vaccination policy options for improving the control of measles in
      Canada is investigated using a mathematical model to simulate transmission of the
      disease. Results suggest that a catch up campaign giving a second dose of vaccine
      to children aged up to 18 years would have an immediate impact on transmission,
      which could be maintained by the introduction of a routine second dose at either
      18 months or 5 years of age. Introducing a routine second dose of vaccine without
      a catch up campaign would allow continued endemic transmission of measles among
      older children for at least 10-15 years.

PMID- 9627937
TI  - Virulence, immunogenicity and reactivation of bovine herpesvirus 1 mutants with a
      deletion in the gC, gG, gI, gE, or in both the gI and gE gene.
AB  - Within the framework of developing a marker vaccine against bovine herpesvirus 1
      (BHV1), several mutants with deletions in non-essential glycoprotein genes were
      constructed. Glycoprotein gC, gG, gI and gE single deletion mutants, a gI/gE
      double deletion mutant and a gE frame-shift mutant were made. The virulence and
      immunogenicity of these mutants were evaluated in specific-pathogen-free calves.
      Except for the gC deletion mutant, all mutants were significantly less virulent
      than the parental wild-type (wt) BHV1 strain Lam. The virulence of the gI and the
      gI-/gE- mutants was almost completely reduced. Upon challenge infection, the
      calves of the control group became severely ill, whereas all other calves
      remained healthy. The reduction of the virus shedding after challenge infection
      was related to the virulence of the strain of primary inoculation. Virus shedding
      was almost completely reduced in calves first inoculated with Lam-wt or with gC-
      and the least reduced in calves inoculated with gI- or gI-/gE-. Six weeks after
      challenge, all calves were treated with dexamethasone to study whether mutant or
      challenge virus or both could be reactivated. The gC- and the gG- mutants were
      reactivated, whereas none of the other mutants were reisolated. Reactivation of
      challenge virus was reduced in all calves inoculated with mutant viruses. The gC
      deletion mutant was too virulent and the gI and the gI/gE deletion mutants were
      the least immunogenic, but based on residual virulence and immunogenicity, both
      the gG and the gE deletion mutants are candidates for incorporation in live BHV1
      vaccines. However, it also depends on the kinetics of the anti-gG and anti-gE
      antibody response after wild-type virus infection, whether these deletion mutants
      are really suitable to be incorporated in a marker vaccine.

PMID- 9627938
TI  - Protective efficacy of a recombinant protective antigen against Bacillus
      anthracis challenge and assessment of immunological markers.
AB  - The efficacy of recombinant Bacillus anthracis Protective Antigen (rPA) produced
      in Bacillus subtilis and formulated in Alhydrogel or MPL-TDM-CWS (Ribi adjuvant)
      has been tested and compared to the licensed UK human vaccine in guinea pigs
      challenged by the aerosol route with the Ames strain of B. anthracis. rPA
      combined with the Ribi adjuvant was found to be the only formulation to provide
      100% protection from challenge. Analysis of immunological parameters in the
      individual animals revealed significant differences between the rPA/Ribi vaccine
      group and rPA/Alhydrogel and human vaccine groups for antigen specific lymphocyte
      proliferation, PA neutralisation and antigen specific IgG2 levels, but indicated
      no significant differences in PA-specific IgG1 levels. rPA formulated in
      Alhydrogel induced a mainly IgG1 response whilst the rPA/Ribi vaccine produced a
      predominantly IgG2 response.

PMID- 9627939
TI  - Field evaluation of the clinical effectiveness of vaccines against pertussis,
      measles, rubella and mumps. The Benevento and Compobasso Pediatricians Network
      for the Control of Vaccine-Preventable Diseases.
AB  - Beginning in March 1995, in the adjacent provinces of Benevento and Campobasso in
      Southern Italy, we carried out a sentinel, paediatrician-based surveillance on
      pertussis, measles, rubella and mumps with the aim of evaluating the health
      impact of new vaccination programmes and the objectives of describing the time
      space trends and estimating the effectiveness of new vaccinations. The study
      population consisted of 16,500 children attended by 25 paediatricians. The
      estimated effectiveness of vaccines for pertussis, measles and rubella were close
      to the expected values, although a very low effectiveness was calculated for the
      mumps vaccine. The comparison among children vaccinated with various strains
      showed a diseases odds ratio of 2.5 for the children vaccinated with Rubini
      strain. The effectiveness of this strain has to be verified in more rigorous
      settings.

PMID- 9627940
TI  - Pools of lipidated HTL-CTL constructs prime for multiple HBV and HCV CTL epitope
      responses.
AB  - Various peptide-based approaches to simultaneous induction of multiple cytotoxic
      T lymphocyte (CTL) responses were evaluated as part of ongoing efforts to develop
      immunotherapeutic vaccines for use in humans. To this end, HLA (human
      histocompatibility leukocyte antigen)-A2-restricted epitopes from several
      specific viral proteins were tested in an HLA-A2 transgenic mouse model system,
      which mimics human CTL responses to these viral proteins. Multiple CTL responses
      were elicited by immunization with either peptides emulsified in incomplete
      Freund's adjuvant (IFA), or lipidated peptides administered in phosphate buffered
      saline (PBS). In the case of lipidated peptides, induction of CTL responses was
      crucially dependent on the presence of helper T lymphocyte (HTL) epitopes, and
      most efficient in the case of lipidated covalently linked HTL-CTL epitope
      constructs. CTL could also be induced by immunization with lipidated HTL epitopes
      simply mixed with CTL epitopes and formulated in PBS. However, this approach was
      highly dependent on the particular lipidated HTL/CTL combination utilized, and
      was marginally effective for simultaneous priming of multiple CTL responses. By
      contrast, all HTL/CTL combinations were potent immunogens when delivered as
      lipidated, covalently linked molecules. This was the most effective of the
      approaches analysed in terms of multi-epitope priming, as demonstrated by the
      induction of simultaneous CTL responses to a pool of five different epitopes.

PMID- 9627941
TI  - Immunisation with live attenuated Salmonella dublin expressing a sporozoite
      protein confers partial protection against Theileria parva.
AB  - Cattle immunised with a recombinant form of p67, the major surface antigen of
      Theileria parva sporozoites, have been shown to be protected against parasite
      challenge. In an attempt to simplify the immunisation procedure live attenuated
      Salmonella strains expressing p67 have been constructed and used to induce anti
      p67 immune responses in cattle. All animals immunised with these strains
      developed strong antibody responses to p67. Specific T cell responses could be
      detected in the majority of immunised cattle. Challenge with T. parva sporozoites
      revealed a significant level of protection in immunised calves compared to naive
      control animals or animals inoculated with non-recombinant attenuated Salmonella.

PMID- 9627943
TI  - Systemic immunization with urease protects mice against Helicobacter pylori
      infection.
AB  - The ability of systemic immunization to induce protection against Helicobacter
      pylori infection has been evaluated in a mouse model. It was observed that if
      appropriate formulations and adjuvants were used such immunization elicited in
      outbred Swiss mice levels of protection similar or better than those induced by
      the oral route in the presence of cholera toxin or Escherichia coli heat labile
      toxin. Recombinant urease mixed with adjuvants, which induced strong Th1 and Th2
      responses elicited better protection than urease mixed with adjuvants which
      induced a predominant Th2 type response only. These experiments demonstrate the
      feasibility of parenteral immunization against H. pylori and suggest that an
      appropriate balance between Th1 and Th2 type responses is required to achieve
      complete protection.

PMID- 9627942
TI  - Induction of Japanese encephalitis virus-specific cytotoxic T lymphocytes in
      humans by poxvirus-based JE vaccine candidates.
AB  - Poxvirus-based recombinant Japanese encephalitis (JE) vaccine candidates, NYVAC
      JEV and ALVAC-JEV, were examined for their ability to induce JE virus-specific
      cytotoxic T lymphocytes (CTLs) in a phase I clinical trial. These vaccine
      candidates encoded the JE virus premembrane (prM), envelope (E) and non
      structural 1 (NS1) proteins. The volunteers received subcutaneous inoculations
      with each of these candidates on days 0 and 28, and blood was drawn 2 days before
      vaccination and on day 58. Anti-E and anti-NS1 antibodies were elicited in most
      vaccinees inoculated with NYVAC-JEV and in some vaccinees inoculated with ALVAC
      JEV. Peripheral blood mononuclear cells (PBMCs) obtained from approximately one
      half of vaccines showed positive proliferation in response to stimulation with
      live JE virus. Cytotoxic assays demonstrated the presence of JE virus-specific
      CTLs in in vitro-stimulated PBMCs obtained from two NYVAC-JEV and two ALVAC-JEV
      vaccinees. Cell depletion tests using PBMCs from one NYVAC-JEV recipient
      indicated that the phenotype of CTLs was CD8+CD4-.

PMID- 9627944
TI  - Differential cellular and humoral immune responses to HCV core and HBV envelope
      proteins after genetic immunizations using chimeric constructs.
AB  - Development of a broad based cellular and humoral immune response to hepatitis C
      virus (HCV) structural proteins may be important for eradication of viral
      infection. In previous studies in mice we demonstrated that facilitated DNA-based
      immunization with an HCV core DNA-expression construct stimulated the generation
      of weak cytotoxic T lymphocyte (CTL), helper T cell (Th), and humoral immune
      responses against HCV core related epitopes. To enhance the immunogenicity of
      this non-secreted viral structural protein at both the B- and T-cell level,
      several chimeric HBV-HCV constructs were prepared which were designed to express
      and secrete HCV core protein along with various regions of the hepatitis B
      envelope protein. No secretion of the chimeric proteins into the culture
      supernatant was detected using sensitive radioimmunoassays. However, such
      chimeric proteins were capable of generating CD4+ inflammatory T cell and CD8+
      CTL activity against both HBV and HCV components of the fusion proteins. It was
      determined that the proliferative activity of T cells as well as the humoral
      immune responses to HCV core protein were substantially enhanced by some chimeric
      fusion proteins as compared to the HCV core protein alone. The strength of the
      immune responses appeared directly related to the level of Th1 cytokines produced
      by CD4+ T cells obtained from immunized animals. Further characterization of the
      immune responses stimulated by these DNA constructs studied helped to define some
      of the most immunogenic regions of the chimeric proteins that they encode.

PMID- 9627945
TI  - [Borrelia PCR: diagnostic Problems Constantly Remain? Why the molecular biology
      diagnosis cannot replace clinical examination].

PMID- 9627946
TI  - [Detection of Borrelia DNA in urine using polymerase chain reaction in
      rheumatologic laboratory diagnosis of Lyme borreliosis].
AB  - Borrelia burgdorferi specific DNA has been detected by polymerase chain reaction
      (PCR) in different specimens of patients with Lyme disease (LD). The aim of the
      present study is to evaluate PCR-diagnostic of urine specimens regarding
      rheumatologic diagnosis of Lyme disease. Urine specimens of 77 patients (LD, n =
      34; undifferentiated arthritis (UA), n = 25; arthralgia/myalgia (AM), n = 18) and
      15 controls were investigated. Flagellin gene (60 specimens) or OspA-plasmid (32
      specimens) were used as targets. Sensitivity of the flagellin-nested-PCR was 27%,
      by OspA-nested-PCR only one positive PCR result was found. Despite of low
      sensitivity PCR enabled the correct diagnosis of LD in two patients classified as
      UA. Therefore, PCR can give valuable hints in single cases if LD is clinically
      suspected.

PMID- 9627947
TI  - [Interdisciplinary group therapy for fibromyalgia].
AB  - Fibromyalgia is present in 2% of the general population and leads to impairment
      by chronic pain and fatigue. It does not improve without therapy directed at the
      symptoms of fibromyalgia. We describe our interdisciplinary group treatment for
      patients with fibromyalgia. They received a physical examination, ergometry and
      psychometric tests both at admission and before discharge, and they were
      questioned to the degree and localization of their pain, to fatigue, sleeping
      disorders and functional symptoms. Therapy included information about
      fibromyalgia, learning of coping strategies, relaxation and endurance training.
      Our results show that our interdisciplinary group treatment is effective for
      fibromyalgia and improves anxiety, depression and well being after a period of 5
      weeks of in-patient rehabilitation.

PMID- 9627948
TI  - Inhibition of interleukin-8 synthesis by intraarticular methotrexate therapy in
      patients with rheumatoid arthritis.
AB  - 5 Patients with definite RA and knee effusions under constant doses of DMARD
      therapy were treated with up to 6 intraarticular injections of 10 mg methotrexate
      (MTX) every 3 to 7 days. A matched randomized control group who received a single
      i.a. injection of 40 mg triamcinolone hexacetonide (TC) was monitored according
      to the same protocol. The intraarticular granulocyte counts and IL-8 levels
      decreased in all MTX treated patients on day 10-13 and stayed low in those
      patients who could be re-evaluated after 13 weeks. Compared to the IL-8 levels,
      the other tested cytokine levels showed only minor changes on day 10-13. There
      was no need for re-injection in the TC group during the 13 week study phase. We
      conclude that intraarticular MTX therapy results in a strong decrease of SF
      granulocyte counts. This effect may be due to the impairment of IL-8 mediated
      chemotaxis by decreased IL-8 synthesis in synovial fluid mononuclear cells.
      Clinically, repeated intraarticular MTX therapy results in a worse 13 week
      outcome than i.a. steroid treatment measured in an intention-to-treat analysis.

PMID- 9627949
TI  - Treatment of refractory rheumatoid arthritis with low-dose cyclophosphamide. Long
      term follow-up of 108 patients.
AB  - Although cyclophosphamide (CYC) is an effective drug in the treatment of
      refractory rheumatoid arthritis (RA), the application of this drug in RA has
      largely been abandoned, due to potentially life-threatening adverse events such
      as myelosuppression and cancer development. However, the question remains open,
      whether it is possible to balance the toxicity and the efficacy of CYC with low
      dose therapy. 108 patients with refractory RA or with vasculitic organ
      involvement were treated with 50 mg CYC per day. Joint indices and laboratory
      parameters were gathered prospectively and the occurrence of serious side effects
      was monitored over a median of 10 years. The efficacy was surveyed in six months
      intervals. A 50% improvement of the swollen joint count was required to continue
      therapy. A long-term follow-up was performed to survey the incidence of
      malignancies. 85 patients dropped out within the first year. Only four patients
      were treated for longer than 4 years. In the total cohort, 50 patients were
      withdrawn due to the lack of efficacy, 34 patients had to discontinue because of
      adverse events, and 9 patients dropped out for both reasons. Gastrointestinal
      intolerance was the most frequent adverse event that led to the discontinuation
      of the drug, followed by myelosuppression. Five patients suffered from 6
      malignancies occurring after a median of 4.5 years after cessation of treatment.
      Treatment of RA patients with 50 mg CYC per day resulted in a more favorable rate
      of serious adverse events and a markedly lower incidence of tumors compared to
      the treatment with 75 to 150 mg per day described in the literature. However, the
      long-term efficacy of this regimen was poor in our cohort.

PMID- 9627950
TI  - [Oxaprozin versus diclofenac retard in treated of activated arthrosis].
AB  - AIM: The present study should elucidate the efficacy, patient acceptability, and
      side effect profiles of Oxaprozin and Diclofenac retard when given to patients
      with active primary osteoarthrosis. METHODS: 80 outpatients with active primary
      osteoarthrosis with a radiological grade of II or III in the hip or knee joint
      (mean duration 4 years) were distributed randomly and equally to each treatment
      group. Patients age ranged from 40-66 years (mean age 51 years). After a washout
      period, they received one of the preparations for 6 weeks. Efficiency assessments
      consisted of pain, disturbance of sleep, individual and general functional
      impairment scales, laboratory determinations, and patients global evaluation. For
      statistical analyses Mann-Whitney-U-, Wilcoxon-, and chi 2-tests were applied.
      RESULTS: 74 Patients completed the study successfully, whereas 3 patients of each
      group withdrew due to adverse events. Significant differences favoring Oxaprozin
      were found for the individual and functional impairment scale and the patients'
      global evaluation of treatment at the final visit (6 weeks). Improvement compared
      to baseline visit was significant for both treatment groups. CONCLUSIONS: The
      results suggest that Oxaprozin is more effective than Diclofenac retard, a
      recognized standard therapy, when given for 6 weeks to patients with active
      osteoarthrosis.

PMID- 9627951
TI  - [Concomitant dermatitis herpetiformis Duhring, arthritis and Sjogren syndrome in
      a patient with celiac disease].
AB  - We report on a 26 year old woman with dermatitis herpetiformis Duhring, diagnosed
      at 10 years of age, who developed arthritis, symptoms of celiac disease, and
      Sjogren's syndrome 15 years later. Clinical symptoms, biopsies of duodenal mucosa
      and salivary glands as well as serological findings established the diagnoses. A
      coincidence of these pathologies has not been reported before. Gluten-free diet
      alleviated severity of clinical symptoms very quickly indicating the basic
      pathology of celiac enteropathy in the immunological disorders.

PMID- 9627952
TI  - [Iloprost administration over 21 days as an effective therapy in systemic
      scleroderma--case report and review of the literature].
AB  - A 57-years old female patient with systemic sclerosis underwent a prolonged
      intravenous therapy during 21 consecutive days with iloprost, a stable analogue
      of prostacyclin. Beginning with 0.5 ng/ kg/minute the dose was increased every 2
      days up to 2 ng/kg/minute. At the end of follow up, Iloprost was shown to enhance
      the perfusion of the finger and to improve pulmonary-function tests including the
      diffusion-capacity. Furthermore, the Erythrocyte Sedimentation Rate and the C
      reactive protein decreased. The case report shows the necessity of a controlled
      study of prolonged iloprost therapy.

PMID- 9627954
TI  - In vitro association between the virulence proteins, YopD and YopE, of Yersinia
      enterocolitica.
AB  - The virulence plasmid (pYV) of Y. enterocolitica encodes a set of anti-host
      proteins, known as Yops, which contribute to survival of the bacteria in the
      host. Several Yops directly influence the interaction of pathogenic bacteria with
      host cells which in the case of at least four Yops, YopE, YopH, YopM and YpkA
      (YopO), involves translocation of the Yop across the eukaryotic cell membrane
      into the cytoplasm of target cells. Translocation requires the presence of two
      other pYV-encoded proteins, YopB and YopD, but it is not clear how these proteins
      mediate translocation of the effector Yops. We have used an affinity blot
      technique (overlay) to examine potential binding between YopD and other Yops. The
      results indicated that under the in vitro conditions used in this study, YopD
      bound preferentially to YopE and YopB. To investigate the interaction of YopD and
      YopE in more detail we produced different regions of the YopD protein in
      Escherichia coli by creating fusions of YopD with glutathione S-transferase.
      These studies showed that YopE bound the central hydrophobic region of YopD. This
      is the first demonstration of protein interactions between an effector Yop and a
      putative Yop translocator.

PMID- 9627953
TI  - Novel metallo beta-lactamase mediated by a Shigella flexneri plasmid.
AB  - Novel carbapenem-hydrolyzing beta-lactamase (newly named MET-1) encoded on a
      transferable plasmid pMS390 from Shigella flexneri JS19622 was purified. The
      molecular weight was 28,000 by SDS-PAGE and the isoelectric point was higher than
      9.3. This beta-lactamase favorably hydrolyzed classical cephalosporins and
      oxyimino-cephalosporins rather than penicillins and carbapenems, but did not
      hydrolyze monobactams. The enzymatic activity was inhibited by EDTA, and the
      enzyme was found to contain two moles of zinc per mole of enzyme protein by means
      of atomic absorption spectrophotometry. These results indicated that the enzyme
      is a zinc beta-lactamase which differs from known metallo beta-lactamases,
      especially in its cephalosporinase-type substrate profile.

PMID- 9627955
TI  - False positive diagnosis of meningococcal infection by the IS1106 PCR ELISA.
AB  - At a time when optimal case ascertainment for meningococcal infection is a high
      priority, the need for non-culture case confirmation, in particular by DNA
      amplification, is seen as being of vital importance to assist contact management
      and cluster recognition. A solution hybridisation assay with colorimetric
      microtitre plate detection (polymerase chain reaction-enzyme-linked immunosorbent
      assay (PCR ELISA)? has been developed using the multicopy insertion sequence
      IS1106 which had reportedly achieved a specificity of 100% and was described as
      being meningococcal specific. This PCR ELISA assay was evaluated on specimens
      from over 5000 patients at the national Meningococcal Reference Unit (MRU)
      between late 1995 and early 1997 and was found to be highly sensitive. Insertion
      sequences, however, are genetically mobile with the ability to spread between
      species and even genera. During the evaluation period of the IS1106 PCR ELISA a
      number of false positives proved to be caused by organisms other than N.
      meningitidis were recorded resulting in the withdrawal of this assay as a front
      line screening assay for routine confirmation of meningococcal infection.

PMID- 9627956
TI  - A molecular view of microbial diversity in a dynamic landfill in Quebec.
AB  - An Aroclor 1260 (polychlorinated biphenyl, PCB)-laden soil and one heavily
      contaminated with polycyclic aromatic hydrocarbons (PAHs) from a secure,
      engineered landfill site in Quebec were analyzed for microbial diversity using a
      clone library of the 16S rDNA sequences. Phylogenetic analysis revealed that
      three phyla and their major subdivisions of the domain Bacteria were highly
      represented in these samples despite the high pollution, particularly by PAHs.
      None of the 16S rDNA sequences obtained matched known sequences from cultivated
      bacterial species or from 16S rDNA sequences amplified directly from other
      environmental samples.

PMID- 9627957
TI  - The binding and utilization of hemoglobin by Prevotella intermedia.
AB  - Prevotella intermedia, a putative periodontopathic microorganism, requires iron
      for growth. Hemoglobin can be a major source of iron for bacterial growth in vivo
      since it is present in the crevicular fluid collected from periodontitis sites.
      Experiments studying the growth of P. intermedia in iron-depleted Todd-Hewitt
      broth supplemented with human hemoglobin showed that the bacteria were able to
      utilize human hemoglobin as a source of iron. The uptake of iron from hemoglobin
      by P. intermedia appears to be initiated by the binding of hemoglobin to the
      bacteria as shown by direct binding studies using 125I-labeled human hemoglobin.
      Scatchard analysis of saturation binding data revealed that 125I-labeled human
      hemoglobin had a dissociation constant (Kd) of 2.53 x 10(-8) M for the receptor
      on P. intermedia. Binding of labeled hemoglobin to P. intermedia was
      competitively inhibited by unlabeled human hemoglobin showing that the binding
      was specific. The ability of bovine hemoglobin, but not hemin or non-hemoglobin
      heme-containing compounds, to inhibit binding competitively suggested that the
      globin moiety of the hemoglobin molecule is recognized by the hemoglobin binding
      receptors.

PMID- 9627958
TI  - Association of genes encoding P fimbriae, CS31A antigen and EAST 1 toxin among
      CNF1-producing Escherichia coli strains from cattle with septicemia and diarrhea.
AB  - Fifty-six CNF1-producing Escherichia coli strains isolated from cattle with
      diarrhea or septicemia were screened by PCR for the detection of pap, sfa, afa,
      clpG, or f17 adherence factor and EAST 1 toxin genes. All the isolates were pap
      positive, in accordance with the close association of pap, CNF1 and alpha
      hemolysin genes observed on human and porcine E. coli. Only the gene encoding the
      P adhesin of class III (PrsG) was detected. Genes encoding CS31A antigen (71%)
      and S fimbriae (34%) (but not Afa or F17) were detected among the bovine
      isolates. E. coli producing both CNF1 and plasmid-encoded CS31A is a new example
      of association between bacterial clones and plasmid-mediated virulence factors.
      The EAST 1 toxin-encoding gene was detected on 66% of the CNF1-producing isolates
      but was linked to CS31A rather than to CNF1. These results suggest a close
      association between EAST 1 toxin and the adherence factor CS31A among pathogenic
      bovine E. coli.

PMID- 9627959
TI  - Isolation and cloning of a Azospirillum lipoferum locus that complements
      Escherichia coli proU mutant.
AB  - Glycine betaine relieved sodium chloride-mediated inhibition of growth in
      Azospirillum lipoferum ATCC 29708. 35S-methionine labelling of proteins after
      salinity up-shock revealed strong induction of a 30 kDa protein which cross
      reacted with the anti-glycine betaine binding protein antibody from Escherichia
      coli. This suggested that A. lipoferum had a salinity-induced ProU-like high
      affinity glycine betaine transport system. A genomic library of A. lipoferum ATCC
      29708 was screened for the proU-like gene by complementation of a proU mutant of
      E. coli. Four recombinant cosmids, capable of restoring growth of the proU mutant
      on plates containing 600 mM NaCl and 1 mM glycine betaine were selected. Selected
      recombinant cosmids hybridized with a proU gene probe from E. coli.
      Complementation of E. coli proU mutant with the A. lipoferum genomic DNA was
      evident by the ability of proU mutant (containing selected recombinant cosmids)
      to grow on minimal medium supplemented with 600 mM NaCl and 1 mM glycine betaine.

PMID- 9627960
TI  - Green fluorescent protein-cell wall fusion proteins are covalently incorporated
      into the cell wall of Saccharomyces cerevisiae.
AB  - Tagging of two cell wall mannoproteins, Cwp1p and Cwp2p, in Saccharomyces
      cerevisiae with the green fluorescent protein from Aequorea victoria resulted in
      incorporation of fluorescent fusion proteins into the cell wall. Both living
      cells and isolated cell walls became brightly labeled. Intriguingly, the
      incorporation patterns of both fusion proteins differed. Western analysis of
      enzymatically released fusion proteins showed that they were covalently linked to
      the beta-1,6-glucan part of the cell wall. Removal of the glycosylphosphatidyl
      inositol anchor signal sequence of the green fluorescent protein-cell wall
      protein fusion proteins resulted in secretion of the proteins into the culture
      medium. These results indicate that green fluorescent protein-cell wall protein
      fusion proteins can be used as a convenient fluorescent marker to study the
      incorporation of specific cell wall proteins and the control mechanisms involved.

PMID- 9627961
TI  - Dissimilatory ATP sulfurylase from the hyperthermophilic sulfate reducer
      Archaeoglobus fulgidus belongs to the group of homo-oligomeric ATP sulfurylases.
AB  - In the hyperthermophilic sulfate reducer Archaeoglobus fulgidus DSM 4304T, two
      open reading frames (sat and ORF2) are located upstream of the aprBA genes
      encoding adenosine-5'-phosphosulfate (APS) reductase. sat-ORF2-aprBA probably
      form a transcriptional unit, since sat is preceded by putative promoter sequences
      and termination signals are found downstream of aprA. While the 117-residue ORF2
      product does not show significant similarity to known proteins, the 456-residue,
      52.78-kDa, sat-encoded polypeptide exhibits similarity to the homo-oligomeric
      adenosine triphosphate (ATP) sulfurylases from sulfur-oxidizing bacteria and from
      sulfate-assimilating bacteria and eukaryotes. Functional overexpression of sat in
      Escherichia coli proved that the encoded protein acts as an ATP sulfurylase. The
      recombinant protein was purified to homogeneity and found to be a homo-dimer.
      Comparison of sulfate and thiosulfate grown A. fulgidus revealed that ATP
      sulfurylase and APS reductase are constitutive enzymes. Distance matrix analyses
      allowed insights into the evolution of prokaryotic ATP sulfurylases.

PMID- 9627962
TI  - The two-component lysis system of Staphylococcus aureus bacteriophage Twort: a
      large TTG-start holin and an associated amidase endolysin.
AB  - The lysis genes of the virulent Staphylococcus aureus bacteriophage Twort were
      cloned and their nucleotide sequences determined. The endolysin gene plyTW
      encodes a 53.3-kDa protein, whose catalytic site is located in the amino-terminal
      domain. An enzymatically active fragment (N-terminal 271 amino acids) was
      overexpressed in Escherichia coli and partially purified. The enzyme rapidly
      cleaves staphylococcal peptidoglycan, and was shown to act as N-acetylmuramoyl-L
      alanine amidase (EC 3.5.1.28). Significant sequence homology to the specific cell
      wall targeting domain of lysostaphin was observed in a 101-amino acid C-terminal
      overlap. However, we found that the large C-terminal portion (63%, 295 aa) of
      PlyTW is not required for staphylolytic activity. Located upstream of and
      overlapping plyTW by 35 bp in a different reading frame (+1), we identified
      holTW, which starts with a single TTG triplet. The gene specifies a 185-amino
      acid (20.5 kDa) holin protein, which features two potential hydrophobic,
      antiparallel transmembrane domains, and a highly charged, acidic C-terminus.
      HolTW is the largest class II holin described to date. It can substitute for the
      defective allele in phase lambda S' amber mutants, both in trans from an
      expression plasmid, and from within gt11::holTW. The proposed function is the
      formation of unspecific membrane lesions to promote access of the endolysin to
      the bacterial peptidoglycan.

PMID- 9627963
TI  - A PCR-based method to distinguish fungi of the rice sheath-blight complex,
      Rhizoctonia solani, R. oryzae and R. oryzae-sativae.
AB  - Identification of Rhizoctonia solani, R. oryzae and R. oryzae-sativae, components
      of the rice sheath disease complex, is extremely difficult and often inaccurate
      and as a result may hinder the success of extensive breeding programmes
      throughout Asia. In this study, primers designed from unique regions within the
      rDNA internal transcribed spacers have been used to develop a rapid PCR-based
      diagnostic test to provide an accurate identification of the species on rice.
      Tests on the specificity of the primers concerned showed that they provide the
      means for accurate identification of the Rhizoctonia species responsible for
      sheath diseases in rice.

PMID- 9627964
TI  - Thin aggregative fimbriae enhance Salmonella enteritidis biofilm formation.
AB  - Salmonella enteritidis enteropathogens produce a variety of potentially adherent
      fimbrial types including SEF14, SEF17, SEF18 and SEF21 (type I). In a simplified,
      pure culture, biofilm generating system the virulent isolate, S. enteritidis 3b,
      readily adhered to Teflon (polytetrafluoroethylene) and stainless steel forming
      thick cell aggregates. The inability of an isogenic SEF17-deficient mutant to
      form thick biofilms suggested a role for SEF17 in stabilizing cell-cell
      interactions during biofilm formation. Epifluorescent detection of SEF17 in
      biofilms confirmed the association of these fimbriae with aggregated cells but
      not with adherent mutants unable to produce SEF17. The reduced adherence observed
      with an isogenic SEF14/SEF21-deficient strain implicated the involvement of
      additional cell surface adherence factors, possibly including SEF21 (type I)
      fimbriae in the adherence of S. enteritidis to stainless steel or Teflon. The
      role of SEF17 fimbriae in biofilm formation and the contributions of SEF17 to the
      persistence of Salmonellae on surfaces and in food are discussed.

PMID- 9627965
TI  - Two highly related regulatory proteins, Shigella flexneri VirF and
      enterotoxigenic Escherichia coli Rns, have common and distinct regulatory
      properties.
AB  - The Rns protein of enterotoxigenic Escherichia coli (ETEC) and the VirF protein
      of Shigella flexneri are members of the AraC family of transcription regulators.
      Rns is required for positive activation of the CS1 fimbrial genes, while VirF is
      a positive regulator of an invasion gene regulon. The amino acid sequences of the
      proteins are 36% identical, and both proteins activate transcription in response
      to increases in temperature. Here, we show that Rns is capable of complementing
      fully a null mutation in the S. flexneri virF gene. However, the VirF protein
      cannot replace Rns as an activator of CS1 gene expression in ETEC. This failure
      is not due to the absence from ETEC of a co-factor required by VirF since it also
      occurs when the CS1 system is moved into an S. flexneri genetic background. Nor
      is it a function of growth medium composition or a failure in virF gene
      expression. Instead, these findings point to important differences in the
      mechanisms by which these related transcription factors regulate gene expression
      in Gram-negative pathogens.

PMID- 9627966
TI  - Expression of the K54 and O4 specific antigen has opposite effects on the
      bactericidal activity of squalamine against an extraintestinal isolate of
      Escherichia coli.
AB  - Squalamine is a novel cationic steroid that possesses potent, broad spectrum,
      antimicrobial activity. Recent data suggests that squalamine or related compounds
      may be present and important in host resistance to infection in the urinary
      tract. Therefore, the role of the K54 capsule and the O4 specific antigen moiety
      of the lipopolysaccharide in protecting an extraintestinal isolate of Escherichia
      coli against the bactericidal activity of this novel antimicrobial compound was
      studied. The O4 specific antigen was important for protection against squalamine.
      Surprisingly, in contrast, the presence of the K54 antigen enhanced the
      bactericidal activity of squalamine. This is the first example, to our knowledge,
      in which an established virulence trait, the K54 capsule, may be detrimental to
      an infecting pathogen under certain circumstances.

PMID- 9627967
TI  - Analysis of plasmid pMZ1 from Micromonospora zionensis.
AB  - Plasmid pMZ1, isolated from Micromonospora zionensis, was also able to replicate
      by the rolling circle mechanism in Micromonospora melanosporea and Streptomyces
      lividans. Southern hybridisation experiments with probe prepared from pMZ1 and
      immobilised M. zionesis DNA fragments separated on pulsed-field gel
      electrophoresis, indicated that the plasmid is present in the progenitor strain
      in both integrated and autonomous states. Thiostrepton resistant derivatives of
      pMZ1 plasmid, pMZS25 and pMZS34, were used to study conjugal transfer in M.
      melanosporea and S. lividans. A 3.4 kb NcoI-MluI fragment from pMZ1 cloned in
      pIJ702 (plasmid pIJNM3) was shown to be sufficient to promote plasmid transfer
      and pock formation in S. lividans.

PMID- 9627968
TI  - Cloning, characterization, and expression of the CIP2 gene induced under cadmium
      stress in Candida sp.
AB  - We isolated, sequenced, and expressed a cadmium-induced gene, CIP2, that
      specifically hybridizes to a mRNA of approximately 950 nucleotides. The CIP2 mRNA
      was barely present in normal Candida cells, but accumulated at higher levels in
      cadmium-treated cells. Other heavy metals such as copper, mercury, lead, and
      manganese had no effect on the expression of the CIP2 gene. CIP2 contains an open
      reading frame encoding a protein of 203 amino acids. This gene was also activated
      by an oxidant, diamide. Our results suggest that CIP2 may play a crucial role in
      the specific cellular response to oxidative stress evolved by the cadmium
      treatment.

PMID- 9627969
TI  - Variation in Bordetella bronchiseptica lipopolysaccharide during human infection.
AB  - We previously reported the case of a human chronic Bordetella bronchiseptica
      respiratory infection, due to contact with infected rabbits. Lipopolysaccharides
      of the human isolates, of one rabbit isolate and of isolate from other origins
      were analyzed with sera from infected mice, rabbit and human. Antigenicity and
      length of the lipopolysaccharide molecules varied between isolates. We showed a
      progressive loss of O-chain during infection, associated with an enhanced
      susceptibility of the isolates to the bactericidal effect of normal serum. This
      observation suggests the existence of an intracellular niche which selects for
      strains with distinct lipopolysaccharide types.

PMID- 9627971
TI  - A comparison of the ability of experts and non-experts to differentiate between
      adult and child human bite marks using receiver operating characteristic (ROC)
      analysis.
AB  - Fifty colour prints of human bite marks were sent to 109 observers who were asked
      to decide using a six point rating scale, whether the marks had been produced by
      the teeth of an adult or a child. The observers consisted of accredited senior
      forensic dentists, accredited junior forensic dentists, general dental
      practitioners, final year dental students, police officers and social workers.
      The results were compared against a "gold standard" which was the actual verdict
      from the case. Comparison of the results between the groups of observers and the
      standard was made using Receiver Operating Characteristics (ROC) methodology. The
      best decisions were made by senior/junior experts or final year dental students.
      General dental practitioners and police officers were least able to differentiate
      correctly between adult and child bite marks. The effect of training is important
      and its effects need to be assessed in more detail in future studies.

PMID- 9627970
TI  - Body-packing as cause of unexpected sudden death.
AB  - Four fatalities related to smuggling of drugs by body-packing were investigated.
      The victims were examined at the Institute of Forensic Medicine of Hamburg
      University between 1983 and 1995, two of them due to "sudden" unknown cause of
      death. All victims were male. Two of them were found already dead in a backyard
      and in a hotel, two other were emergency cases and died at a hospital. Smuggled
      substances included cocaine (two cases), heroin and amphetamine/caffeine. In all
      cases, the cause of death was intoxication caused by torn packages which were
      detected at autopsy. The maximum weight of the packet's contents was 630 g
      divided in 90 packages. Only one victim was apparently an intravenous drug
      abuser. Hair analysis was performed in three cases and revealed in one case a
      difference between a concealed and a habitually consumed drug. Toxicological
      analysis revealed that the substances were quite pure and provided evidence that
      rather long survival was possible following intoxication in three cases, in two
      cases supported by hospital treatment in the final stage. The procedural regimen
      in cases of suspected body-packing is discussed.

PMID- 9627972
TI  - Study of rearrests for drunken driving in Norway.
AB  - The National Institute of Forensic Toxicology (NIFT) in Oslo receives blood
      samples from all Norwegian drivers suspected of driving under the influence of
      alcohol. It is well known that a large proportion of the arrested drunken drivers
      are repeat offenders. The purposes of this investigation was to find the arrest
      rates (the percentage of subjects arrested once or more) among drunken drivers
      followed retrospectively and prospectively during the 11-year period 1984-1994
      and the probability of 'abstaining' from becoming a recidivist during the 9 years
      subsequent to the year of selection. By examining the rearrest rates during the 3
      following years for drivers selected in 1986, 1989, 1991 and 1992 we tried to
      look for major effects due to the change in the Norwegian road traffic act of
      1988. Altogether 45% of the selected drunken drivers were arrested two or more
      times. Totally the '9-year survival rate' (i.e. not being rearrested) was 60% for
      drivers with blood alcohol concentration (BAC) selected from the interval 0.06
      0.09%; 56% from BAC 0.13-0.16% and 51% from 0.26-0.29%. The data were further
      evaluated with respect to frequency of rearrest during 3 years after selection,
      and was around 30% in 1986, while it was lower for drivers selected in 1992
      (19%). An explanation for the reduction in rearrest rate may be the changes in
      the road traffic act which took place in 1988.

PMID- 9627973
TI  - Incidence of opiates, amphetamines, and cocaine in hair and blood in fatal cases
      of heroin overdose.
AB  - The purpose of the present study was to investigate the occurrence in hair, of
      some drugs of abuse in deaths caused by heroin overdose, in comparison to
      findings in blood. Blood, urine and hair samples were obtained during routine
      post mortem examinations. Samples were analysed for amphetamines, opiates, and
      cocaine. Immunometric drug screening was performed in urine and positive results
      confirmed with gas chromatography-mass spectrometry (GC-MS) of blood samples. All
      hair samples were analyzed with GC-MS. Hair samples were either incubated with
      methanol for determination of opiates and cocaine, or dissolved in sodium
      hydroxide for determination of amphetamines. All 19 blood samples were positive
      for morphine (0.04-0.4 microgram g-1) and ten were also positive for 6
      acetylmorphine (0.003-0.02 microgram g-1). Thirteen of the hair samples were
      positive for 6-acetylmorphine and seven of which were positive also for morphine.
      Concentrations ranged from 0.3-7.4 and 0.3-1.3 (ng mg-), respectively.
      Amphetamine was found in three blood samples (0.04-1.2 micrograms g-1) and in
      eleven hair samples (0.4-18.3 ng mg-). Cocaine was determined in one blood sample
      (0.03 microgram g-1) and two hair samples (0.7-6.5 ng mg-). Out of the nineteen
      cases studied, eight showed chronic multi drug use on the basis of the results of
      hair analysis. In six subjects no opiates could be detected in hair, suggesting;
      "first" or occasional intake of heroin, which could be a contributing factor to
      the overdose death, because of lack of tolerance. We conclude that analysis of
      hair can be a useful complement to analysis of more conventional autopsy
      material, especially when investigating overdose deaths and previous histories of
      drug use and abuse.

PMID- 9627974
TI  - Medicolegal autopsies of violent deaths in northern Norway 1972-1992.
AB  - The aim of this paper is to describe the characteristics of medicolegal autopsies
      of violent deaths in northern Norway over a period of 20 years. On request by the
      police, 1446 violent deaths were examined--82.6% males and 17.4% females. The
      mean age was 40.2 years (range 0-98). The most frequent violent manners of death
      were suicides (24.9%), deaths caused by motor vehicle traffic accidents (18.6%),
      accidental poisoning (11.5%) and boating incidents (8.4%). Homicides and
      involuntary manslaughter came to 4.4% and 1.7%, respectively, whereas in 11.4% of
      cases the manner of death was unknown. The five most frequent causes of death
      were blunt injury (31.4%), drowning (17.4%), suffocation (11.8%), firearm (11.3%)
      and poisoning (10.5%). In 3.5% of the cases the cause of death was unknown. The
      spectrum of the manner of death and the cause of death in a subarctic population
      is discussed with reference to legislation, practise of request and information
      given by the police.

PMID- 9627975
TI  - Identification of 3,4-methylenedioxyamphetamine analogs encountered in
      clandestine tablets.
AB  - Recently, 3,4-methylenedioxyamphetamine derivatives have been encountered in the
      Italian illicit market, mainly in form of tablets. Among this class of substances
      small modifications of the molecule may result in a wide range of derivatives and
      analogs some of which are not yet listed as controlled substances in the Italian
      schedules. Due to the structural similarity some of these molecules have a gas
      chromatographic behavior and mass spectra that only slightly differ. In the
      present work, an analytical strategy is proposed to achieve the identification of
      analogs within this class of molecules. In seized material sent by the Court of
      Law of Rome to our laboratories a number of tablets engraved with different
      symbols (e.g., 'Dollar', 'Fido Dido' and 'Bomb') were submitted to analysis in
      order to establish whether they contained drugs of abuse. The analytical
      techniques employed for this purpose were UV spectrophotometry and thin-layer
      chromatography which provided information suggesting that the tablets contained a
      methylenedioxyamphetamine. Gas chromatography with flame ionization detection
      indicated that the main ingredient differed from the molecules of the same class
      already known. Finally, capillary gas chromatographic-mass spectrometric analysis
      of the native molecules and their pentafluoropropionic acid derivatives,
      performed with both, electron impact and chemical ionization, allowed the
      identification, in each tablet, of three molecules: the N-methyl-1-(3,4
      methylenedioxyphenyl)-2-butanamine (MDP-2-MB, MBDB), the 1-(3,4
      methylenedioxyphenyl)-2-butanamine (MDP-2-B) and the N,N-dimethyl-1-(3,4
      methylenedioxyphenyl)-2-butanamine (MDP-2-MMB).

PMID- 9627976
TI  - Validation of a high performance liquid chromatographic method for alpha amanitin
      determination in urine.
AB  - The objective of the present study was to develop and validate a liquid
      chromatographic method with electrochemical detection to measure alpha amanitin
      concentrations in urine after sample pretreatment with double mechanism (reversed
      phase/cation exchange) solid-phase extraction cartridges. The urine samples (10
      ml) were purified and concentrated to 1 ml with elimination of matrix
      contaminants. The extracts were then separated by isocratic reversed-phase
      chromatography using a C18 column (4.6 mm x 25 cm) with a mobile phase composed
      of 0.005 M phosphate buffer (pH 7.2) and acetonitrile (90:10). Coulometric
      detection was performed by applying an oxidation potential of +500 mV to a porous
      graphite electrode in a low-volume analytical cell. The limit of quantitation was
      10 ng/ml with a signal-to-noise ratio = 25. The linearity studied on spiked urine
      was satisfactory (r = 0.9966) from 10 ng/ml to 200 ng/ml. The average extraction
      recovery of alpha amanitin was 78%, determined using spiked urine samples ranging
      from 10-300 ng/ml. The intra-assay precision was checked at 10, 50 and 100 ng/ml
      levels (n = 10) in spiked urine samples, with resulting coefficients of variation
      of 3.6%, 2% and 1.5%, respectively.

PMID- 9627977
TI  - Advances in capillary electrophoresis.
AB  - This review summarizes the advancement in operational modes and selected
      applications of the title technique over the past five years. Regarding
      operational modes particular emphasis is put upon increasing selectivity and
      resolution, hyphenation of capillary electrophoresis with techniques based on
      other than electromigration principles, the so-called chip technology and new
      ways of detection. In applications selected examples of chiral separation and
      separation of biopolymers (proteins, nucleic acids) are emphasized. It is
      demonstrated that capillary electrophoresis represents a complementary technique
      to high-performance column chromatography and in a number of cases it offers
      better separations than standard chromatographic procedures.

PMID- 9627978
TI  - Capillary electrophoresis in clinical toxicology.
AB  - During the past decade, capillary electrophoresis (CE) emerged as a promising,
      effective and economic approach for separation of a large variety of substances,
      including those encountered in clinical toxicology. Reliable and automated CE
      instruments became commercially available and promoted the exploration of an
      increasing number of CE methods for illicit and licit drugs in body fluids. The
      widespread applicability of CE, its enormous separation power and high
      sensitivity detection schemes make this technology an attractive and promising
      tool. This review provides an overview of the key achievements encountered with
      CE in clinical toxicology, including (i) the rapid assessment of drug
      intoxications via direct sample injection, (ii) the screening for and
      determination of illicit and licit drugs in body fluids with drug extraction,
      drug concentration (stacking) and chiral discrimination, (iii) the application of
      immunological single and multianalyte assays in the capillary format to the
      screening for drugs in body fluids, and (iv) drug confirmation by on-column
      multiwavelength absorbance and fluorescence detection and/or CE coupled to mass
      spectrometry. With its distinct features (automation, small sample size, minimal
      sample preparation, requirement of almost no organic solvents, ease of buffer
      change and method development, speed of analysis, low cost of capillaries and
      chemicals) CE has a bright future and the twenty-first century will witness the
      widespread use of a large number of simple and reliable CE based assays for
      drugs, methods that will be employed in clinical toxicology, therapeutic drug
      monitoring and forensic science.

PMID- 9627979
TI  - Hair analysis for abused drugs by capillary zone electrophoresis with field
      amplified sample stacking.
AB  - The present paper describes the methodological optimisation and validation of a
      capillary zone electrophoresis method for the determination of morphine, cocaine
      and 3,4-methylenedioxymethamphetamine (MDMA) in hair, with injection based on
      field-amplified sample stacking. Diode array UV absorption detection was used to
      improve analytical selectivity and identification power. Analytical conditions:
      running buffer 100 mM potassium phosphate adjusted to pH 2.5 with phosphoric
      acid, applied potential 10 kV, temperature 20 degrees C, injection by
      electromigration at 10 kV for 10 s, detection by UV absorption at the fixed
      wavelength of 200 nm or by recording the full spectrum between 190 and 400 nm.
      Injection conditions: the dried hair extracts were reconstituted with a low
      conductivity solvent (0.1 mM formic acid), the injection end of the capillary was
      dipped in water for 5 s without applying pressure (external rinse step), then a
      plug of 0.1 mM phosphoric acid was loaded by applying 0.5 psi for 10 s and,
      finally, the sample was injected electrokinetically at 10 kV for 10 s. Under the
      described conditions, the limit of detection was 2 ng/ml for MDMA, 8 ng/ml for
      cocaine and 6 ng/ml for morphine (with a signal-to-noise ratio of 5). The lowest
      concentration suitable for recording interpretable spectra was about 10-20-times
      the limit of detection of each analyte. The intraday and day-to-day
      reproducibility of migration times (n = 6), with internal standardisation, was
      characterised by R.S.D. values < or = 0.6%; peak area R.S.D.s were better than
      10% in intraday and than 15% in day-to-day experiments. Analytical linearity was
      good with R2 better than 0.9990 for all the analytes.

PMID- 9627980
TI  - Analysis of lysergic acid diethylamide: comparison of capillary electrophoresis
      with laser-induced fluorescence (CE-LIF) with conventional techniques.
AB  - The increasing use of the potent hallucinogenic drug D-lysergic acid diethylamide
      (LSD) makes the application of highly sensitive analytical techniques necessary.
      For an effective analysis of biological specimens a limit of detection in the sub
      ng/ml range is required. Using capillary electrophoresis (CE), with laser-induced
      fluorescence detection it was possible to determine 0.1-0.2 ng LSD/ml blood. The
      conventionally used immunoassays and gas and high-performance liquid
      chromatographic methods have cut-off values and limit of detection, respectively,
      in the same range. Only tandem mass spectrometry techniques can be more
      sensitive. Therefore, CE can be considered a good complementary method to
      conventional immunological and chromatographic techniques for the forensic
      analysis of biofluids.

PMID- 9627981
TI  - Analysis of methaqualone in biological matrices by micellar electrokinetic
      capillary chromatography. Comparison with gas chromatography-mass spectrometry.
AB  - The analysis of methaqualone (MTQ) in biological matrices by capillary
      electrophoresis (CE) is described. This methods uses liquid-liquid extraction and
      micellar electrokinetic capillary chromatography (MECC), an operation mode of CE.
      Separations are made using a 25 cm long capillary and a borate/phosphate buffer
      at pH 8.2. Using gas chromatography with mass spectrometry detection (GC-MS) as
      reference method, MTQ has been analyzed in urine, blood, gastric content and
      hair. For hair analysis, supercritical fluid extraction was compared with liquid
      liquid extraction. Linearity was established in urine and blood between 0.25 and
      10.0 micrograms/ml. MTQ recovery from blood was estimated at 60%. The limit of
      detection of this method in urine is about 0.10 microgram/ml. Drawbacks and
      advantages of MECC over GC-MS are discussed.

PMID- 9627982
TI  - Recent advances in capillary zone electrophoresis of DNA.
AB  - The present minireview summarizes recent developments in the field of DNA
      separations by capillary zone electrophoresis (CZE), as developed by our group.
      Separation of antisense oligonucleotides in sieving liquid polymers in
      isoelectric buffers is discussed first. It is shown that the use of isoelectric
      buffers permits very high voltage gradients (up to 1000 V cm-1) with much reduced
      transit times and increased resolution of all truncated and failed sequences.
      Oligonucleotides can also be analysed by zone electrophoresis against a
      stationary pH gradient (typically a pH 6.5-10 range): if injected at the alkaline
      end, the sample components experience stacking and zone sharpening due to
      modulation of charge as the oligonucleotides move along the pH gradient.
      Oligonucleotides having the same length, but differing by one single nucleotide
      in the chain, can be separated in free solution (i.e. in the absence of a sieving
      matrix) at strongly acidic pH values (pH 3.0-3.3) where charge differences due to
      base protonation are maximized. By working in free solution, it has also been
      possible to measure accurately the free mobility of DNAs, shown to reach a
      constant value of 3.75 +/- 0.04 10(-4) cm2 V-1 s-1 at 25 degrees C and in Tris
      acetate-EDTA buffer, pH 8.3, above a critical length of ca. 400 base pairs.
      Finally, detection of point mutations in human genomic DNA is proven to be
      feasible in nonisocratic CZE, by running temperature-programmed CZE. The
      temperature gradient is activated within the capillary lumen by voltage ramps
      during the run, by exploiting joule effects. This technique has been proven to
      work for all point mutants, from low-, to intermediate-, to high-melters and has
      been applied to a number of point mutants in cystic fibrosis and thalassemia.

PMID- 9627983
TI  - Polymerase chain reaction typing of D21S11 short tandem repeat polymorphism by
      capillary electrophoresis. Allele frequencies and sequencing data in a population
      sample from central Italy.
AB  - Blood samples were collected from 100 individuals living in Central Italy and
      analysed for STR locus D21S11 by capillary electrophoresis on an ABI Prism 310
      genetic analyzer. For fragment sizing, PCR amplification products, obtained using
      a 6-FAM 5'-labeled reverse primer and an unlabeled forward primer, were run with
      an internal size standard labeled with TAMRA dye and typed using the local
      reciprocal method. An allele ladder consisting of a mix of sequenced amplified
      products was also prepared. An Italian population database was established. No
      deviation from Hardy-Weinberg equilibrium was observed. The result of statistical
      analysis were highly informative (PD = 0.94; mean exclusion change = 0.66). DNA
      sequencing was performed on a set of representative alleles by Taq cycle
      sequencing using dye terminator labeling chemistry. A new structural variant was
      found.

PMID- 9627984
TI  - Quantitation of absolute Pneumocystis carinii nuclear DNA content. Trophic and
      cystic forms isolated from infected rat lungs are haploid organisms.
AB  - The Pneumocystis carinii carinii DNA content in nuclei of trophic forms and cysts
      (spore cases) containing 2, 4, or 8 intracystic bodies, were compared using
      quantitative fluorescence image analysis. The nuclear DNA content was found to be
      lower than the theoretical limits of Feulgen cytophotometry. Several fluorescent
      DNA dyes provide brighter staining, but these techniques suffer from nonspecific
      binding to other cellular components, such as RNA. It was demonstrated that the
      thick glycocalyx surfaces of trophic forms and the cyst walls of P. carinii
      organisms, as well as the cell wall of S. cerevisiae, bound all fluorescent dyes
      tested to varying degrees. Hence in this study, measurements were performed on
      cells in which the outer surfaces of organisms were first removed with lyticase.
      Two stains that appeared most specific for DNA, DB181 and 4',6-diamidino-2
      phenylindole (DAPI), were used for quantitations; lower deviations of
      fluorescence intensities were observed with DB181. Haploid wild type
      Saccharomyces cerevisiae and cdc-28 temperature-sensitive mutant cells,
      accumulated at the restrictive temperature (37 degrees C), were used as
      quantitative internal standards for estimating the absolute nuclear DNA content
      of P. carinii. Haploid wild type and mutant nuclei stained with DAPI had the same
      relative fluorescence intensities. The P. carinii nuclear DNA content of trophic
      forms and individual intracystic bodies (spores), regardless of life cycle stage,
      were not different. The mean values obtained were 6.9 and 6.7 fg DNA/nucleus with
      DB181 and DAPI, respectively (approximately 9.26 and 8.99 Mbp nucleotides,
      respectively). Since these would include 2C (G-2 phase) and S-phase nuclei, a 1C
      population of nuclei was selected by histogram distributions of DB181-stained
      nuclei. Almost all nuclei analyzed in all life cycle stages fell within this
      population. The 1C mean of 6.55 fg DNA/nucleus (median, 6.62 fg DNA/nucleus) was
      estimated as representing 8.79 Mbp nucleotides, assuming only A-T binding of the
      dye and taking into account the G + C content of S. cerevisiae and P. carinii. A
      4C (G-2-phase diploid nuclei) population was not detected in histograms of DB181-
      or DAPI-stained nuclei. The P. carinii nuclear DNA content values obtained in
      this study were similar to those independently obtained by calculating the total
      DNA in the organism's chromosomes resolved by electrophoretic techniques.
      Together, the data on total chromosome numbers and the estimated DNA content of
      those chromosomes, with our quantitation of nuclear DNA content of different life
      cycle stages demonstrate that P. carini carinii isolated from infected rat lungs
      are haploid organisms.

PMID- 9627985
TI  - Brachiola vesicularum, n. g., n. sp., a new microsporidium associated with AIDS
      and myositis.
AB  - Brachiola vesicularum, n. g., n. sp., is a new microsporidum associated with AIDS
      and myositis. Biopsied muscle tissue, examined by light and electron microscopy,
      revealed the presence of organisms developing in direct contact with muscle cell
      cytoplasm and fibers. No other tissue types were infected. All parasite stages
      contain diplokaryotic nuclei and all cell division is by binary fission.
      Sporogony is disporoblastic, producing 2.9 x 2 microns diplokaryotic spores
      containing 8-10 coils of the polar filament arranged in one to three rows,
      usually two. Additionally, this microsporidium produces electron-dense
      extracellular secretions and vesiculotubular appendages similar to Nosema
      algerae. However, the production of protoplasmic extensions which may branch and
      terminate in extensive vesiculotubular structures is unique to this parasite.
      Additionally, unlike Nosema algerae, its development occurred at warm blooded
      host temperature (37-38 degrees C) and unlike Nosema connori, which disseminates
      to all tissue types, B. vesicularum infected only muscle cells. Thus, a new genus
      and species is proposed. Because of the similarities with the genus Nosema, this
      new genus is placed in the family Nosematidae. Successful clearing of this
      infection (both clinically and histologically) resulted from treatment with
      albendazole and itraconozole.

PMID- 9627986
TI  - A PCR screen identifies a novel, unconventional myosin heavy chain gene (MYO1) in
      Tetrahymena thermophila.
AB  - Degenerate primers for two regions of sequence homology in the myosin head domain
      were used in a polymerase chain reaction screen of Tetrahymena thermophila
      genomic DNA to amplify a 765 bp fragment that was cloned and sequenced. Based on
      the presence of conserved, myosin-specific sequences, the 765 bp PCR product was
      identified as a fragment of a myosin gene, the first to be discovered in ciliated
      protozoa and herein referred to as MYO1. An inverse polymerase chain reaction
      strategy was used to obtain additional sequence data that included the entire
      head domain of MYO1. Alignment of the predicted amino acid sequence of the MYO1
      head domain with known myosin sequences identified the ATP-binding site, a
      phosphorylation site, and other myosin-specific consensus regions. In a northern
      blot analysis, a 765 bp MYO1-specific probe detected a 6.6 kb transcript under
      highly stringent hybridization conditions. Phylogenetic analysis revealed that
      the predicted protein encoded by MYO1 is not a member of any of the previously
      defined myosin classes and therefore represents a presumptive new myosin class.

PMID- 9627987
TI  - Microsporidia of the genus Trachipleistophora--causative agents of human
      microsporidiosis: description of Trachipleistophora anthropophthera n. sp.
      (Protozoa: Microsporidia).
AB  - Trachipleistophora anthropophthera n. sp., was found at autopsy in the brain of
      one and in the brain, kidneys, pancreas, thyroid, parathyroid, heart, liver,
      spleen, lymph nodes, and bone marrow of a second patient with AIDS. The parasite
      is similar to the recently described T. hominis Hollister, Canning, Weidner,
      Field, Kench and Marriott, 1996, in having isolated nuclei, meronts with a thick
      layer of electron dense material on the outer face of their plasmalemma and
      sporogony during which spores are formed inside a thick-walled sporophorous
      vesicle. In contrast to T. hominis, this species is dimorphic as it forms two
      kinds of sporophorous vesicles and spores: Type I--round to oval polysporous
      sporophorous vesicle, 7-10 microns in size, usually with eight spores (3.7 x 2.0
      microns), thick endospores, subterminal anchoring disc and anisofilar polar
      filaments forming seven thicker and two thinner terminal coils. This type of
      sporophorous vesicle is associated with 25-30 nm filaments extending into the
      host cell cytoplasm. Type II--smaller, bisporous sporophorous vesicle (4-5 x 2.2
      2.5 microns) with two, nearly round, thin-walled spores, 2.2-2.5 x 1.8-2.0
      microns in size, having 4-5 isofilar coils. No outside filamentous elements are
      associated with the bisporous sporophorous vesicle. Both types of sporophorous
      vesicles were common in the infected brain tissue and could be found within the
      same cell. The newly described species, together with T. hominis and previously
      reported Pleistophora-like parasites from human muscle, likely represent a group
      of closely related human microsporidia.

PMID- 9627988
TI  - Zymolyase treatment exposes p55 antigen of Pneumocystis carinii.
AB  - Rats exposed to Pneumocystis carinii mount antibody responses to a broad band
      migrating on western blot with an apparent molecular weight of 45-55 kDa. One
      antigen within this band, designated p55, is uniformly recognized by P. carinii
      exposed rats. Although the gene encoding the p55 antigen had been previously
      cloned, the location of this antigen within the organism was unknown. Prior
      attempts to localize the protein were unsuccessful. A monospecific polyclonal
      antiserum raised against a carboxyl-terminal 15-oligomer peptide yielded specific
      reactivity with a single 55 kDa band on a western blot of P. carinii. Using this
      antiserum, little to no reactivity could be detected with P. carinii organisms by
      immunofluorescence assay (IFA). However, zymolyase treatment of P. carinii
      dramatically increased the intensity and proportion of organisms reactive by IFA.
      Zymolyase, an enzyme with beta-1,3 glucanase activity, has previously been shown
      to remove the electron dense outer layer of the P. carinii cell wall, exposing an
      electron lucent layer. Immunoelectron microscopy performed on zymolyase treated
      organisms showed the majority of labeling occurs within the cell wall.

PMID- 9627989
TI  - Verification of intermediate hosts in the life cycles of microsporidia by small
      subunit rDNA sequencing.
AB  - Small subunit rDNA sequences were obtained from field-collected Amblyospora
      connecticus (Microsporida: Amblyosporidae) spores isolated from the mosquito,
      Aedes cantator (Diptera: Culicidae), and from field collected spores isolated
      from the putative intermediate host, Acanthocyclops vernalis (Copepoda:
      Cyclopidae). The ribosomal DNA sequences of the spores isolated from the two
      hosts were identical. These findings corroborate previous laboratory transmission
      studies and validate the intermediary role of A. vernalis in the life cycle of
      this microsporidium. These data represent the first comparative sequence analysis
      of a microsporidium isolated from its definitive and intermediate hosts. The
      results demonstrate the effectiveness of using rDNA sequence data for screening
      potential intermediate hosts. Unlike laboratory transmission tests, which can
      take months or years to complete, this technique can be completed in days and can
      be performed on a single infected organism.

PMID- 9627990
TI  - Monophyly of endosymbiont containing trypanosomatids: phylogeny versus taxonomy.
AB  - To obtain additional information on the phylogenetic relationships within the
      family Trypanosomatidae (order Kinetoplastida), we have sequenced the small
      subunit ribosomal RNA genes from the endosymbiont containing species Herpetomonas
      roitmani TCC080, Herpetomonas sp. TCC263, Crithidia oncopelti ATCC 12982 and a
      partial large subunit rRNA gene from H. roitmani. The small subunit sequences in
      the two isolates of Herpetomonas are very similar but not identical, and so are
      their restriction digest profiles of kinetoplast DNA. The size of minicircles in
      both isolates is 4.2 kilobases. The inferred ribosomal RNA phylogenetic trees
      shows the genera Herpetomonas and Crithidia as polyphyletic. Endosymbiont-bearing
      herpetomonads cluster with the endosymbiont-bearing crithidias and a
      blastocrithidia to form a monophyletic clade, whereas the endosymbiont-free
      members of these genera are found elsewhere in the tree. These data support the
      hypothesis of a monophyletic origin of endosymbiosis in trypanosomatid evolution
      and also suggest that a taxonomic revision is needed in order to better describe
      the natural affinities in this family.

PMID- 9627991
TI  - Functional conservation of calreticulin in Euglena gracilis.
AB  - Calreticulin is the major high capacity, low affinity Ca2+ binding protein
      localized within the endoplasmic reticulum. It functions as a reservoir for
      triggered release of Ca2+ by the endoplasmic reticulum and is thus integral to
      eukaryotic signal transduction pathways involving Ca2+ as a second messenger. The
      early branching photosynthetic protist Euglena gracilis is shown to possess
      calreticulin as its major high capacity Ca2+ binding protein. The protein was
      purified, microsequenced and cloned. Like its homologues from higher eukaryotes,
      calreticulin from Euglena possesses a short signal peptide for endoplasmic
      reticulum import and the C-terminal retention signal KDEL, indicating that these
      components of the eukaryotic protein routing apparatus were functional in their
      present form prior to divergence of the euglenozoan lineage. A gene phylogeny for
      calreticulin and calnexin sequences in the context of eukaryotic homologues
      indicates i) that these Ca2+ binding endoplasmic reticulum proteins descend from
      a gene duplication that occurred in the earliest stages of eukaryotic evolution
      and furthermore ii) that Euglenozoa express the calreticulin protein of the
      kinetoplastid (trypanosomes and their relatives) lineage, rather than that of the
      eukaryotic chlorophyte which gave rise to Euglena's plastids. Evidence for
      conservation of endoplasmic reticulum routing and Ca2+ binding function of
      calreticulin from Euglena traces the functional history of Ca2+ second messenger
      signal transduction pathways deep into eukaryotic evolution.

PMID- 9627992
TI  - Heterogeneity and a coiled coil prediction of trypanosomatid-like flagellar rod
      proteins in Euglena.
AB  - The emergent flagellum of euglenoids and trypanosomatids contained in addition to
      microtubules a prominent filamentous structure--the flagellar rod
      (paraflagellar/paraxonemal rod). Immunoblots and immunofluorescence localization
      using three antibodies generated against gel-isolated proteins confirmed previous
      studies that the Euglena flagellar rod consisted of polypeptides migrating at 66
      , 69-, and 75-kD. Immunoblotting after two dimensional gel electrophoresis
      identified ten or more isoforms of these polypeptides. Differences in migration
      in acrylamide gels under nonreducing and reducing conditions suggested that the
      rod proteins contain intramolecular disulfide linkages. Comparative peptide
      mapping showed that the 66-, 69-, and 75-kD polypeptides were distinct, but
      related proteins, and also identified a fourth related protein migrating at 64
      kD. Using antibodies against rod proteins, two overlapping cDNAs were isolated
      and from their sequences the cDNAs were predicted to encode 334 amino acids of
      the 66-kD protein; the amino acid sequence had > 65% identity to the carboxyl
      terminus of the trypanosomatid flagellar rod proteins. Secondary structural
      prediction suggested that flagellar rod proteins contain an extended segmented
      coiled coil stalk and two nonhelical heads. Coiled coil appeared to be an
      important structural motif in the construction of flagellar rod filaments.

PMID- 9627994
TI  - Effect of conditioned media from chicken and turkey intestinal cell cultures on
      invasion by sporozoites of three species of avian coccidia.
AB  - The effect of conditioned media from cultures of turkey and chicken intestinal
      cells on cellular invasion by sporozoites of avian Eimeria species was examined
      in vitro. Media conditioned by the growth of cells from the ceca, mid-intestine
      (area of the yolk stalk diverticulum), and duodenal loop were examined for their
      ability to enhance invasion. Conditioned medium from cultures of turkey cecal
      cells significantly enhanced invasion by the turkey coccidia Eimeria adenoeides,
      by 2.4-fold, and E. meleagrimitis, by 2.2-fold, as compared with invasion in the
      presence of control medium. Conditioned medium from mid-intestinal cell cultures
      enhanced invasion by the two coccidial species by 2.0- and 2.1-fold,
      respectively. The enhancement occurred with conditioned media from early (1) as
      well as later (11) passages of cells. This suggests that the enhancing factor was
      produced by fibroblast-like cells, the predominant cell type at both early and
      late passages, and not by epithelial-like cells that had disappeared by the first
      or second passage. Additionally, conditioned media from cultures of chicken cecal
      and duodenal loop cells significantly enhanced invasion by the turkey cecal
      coccidium, E. adenoeides, (1.7- and 1.6-fold, respectively). This was less
      enhancement than was caused by the turkey cell conditioned media. Heat treatment
      (56 degrees C for 45 min) of conditioned media failed to alter the effect on
      invasion. Neither the turkey or chicken cecal cell media nor conditioned media
      from any other chicken intestinal cell cultures enhanced invasion by E. tenella,
      the chicken cecal coccidium. Although morphologically dissimilar when they were
      first plated, the gross appearance and growth of the turkey and chicken cells
      when conditioned media was collected was comparable.

PMID- 9627993
TI  - Cell wall antigens of Pneumocystis carinii trophozoites and cysts: purification
      and carbohydrate analysis of these glycoproteins.
AB  - We have purified and biochemically analyzed individual cell wall glycoproteins of
      Pneumocystis carinii. Our results show that corresponding core glycoproteins
      constitute the cell wall antigens in both trophozoites and cysts, and
      glycosylation of these glycoproteins does not appear to be significantly altered
      during development. Cysts and trophozoites in rat-derived organism preparations
      were separated from each other by counterflow centrifugal elutriation, then
      treated with Zymolyase to obtain the cell wall fractions. Gel electrophoresis
      patterns of these fractions from both life-cycle stages were qualitatively
      similar. Ten major antigenic glycoproteins in these fractions were purified by
      preparative continuous elution gel electrophoresis. All ten glycoproteins from
      cysts and trophozoites contained mannose, glucose, galactose, and N
      acetylglucosamine, and some contained traces of fucose. The glycoproteins of
      cysts had more mannose than their trophozoite counterparts. The trophozoite
      glycoproteins differed from those of the cyst by the presence of xylose. To
      examine the species-specificity of glycoprotein glycosylation, preparations of
      human-derived P. carinii (comprised of mixed life-cycle stages) were also
      examined and found to contain the same sugars as those found in rat-derived
      organisms. Most of the purified rat-derived glycoproteins bound Concanvalin A,
      which was abolished by treatment with N-glycanase. This suggested that the
      majority of the oligosaccharides were N-linked to the proteins, but attempts to
      identify carbohydrate linkage sites by amino acid sequencing were hampered by
      apparent modifications of residues. The peptides derived by cyanogen bromide
      cleavage revealed distinct size patterns for each glycoprotein, suggesting that
      they were distinct proteins. Most of the glycoproteins reacted with monoclonal
      antibodies which recognize a highly conserved epitope on rat P. carinii. Four of
      the individually purified glycoprotein preparations elicited in vitro cellular
      immune responses, implicating their involvement in the recognition of P. carinii
      by host T cells. The identification and characterization of P. carinii cell wall
      proteins will be helpful in analyzing the relationship of the organism to its
      mammalian host.

PMID- 9627995
TI  - Mechanisms of microsporidial cell division: ultrastructural study on
      Encephalitozoon hellem.
AB  - The mitotic process in microsporidian Encephalitozoon hellem, a known human
      pathogen, has been studied with the aim of elucidating some ultrastructural
      aspects of its nuclear division. The presence of a nuclear spindle, of
      "electrondense spindle plaques" associated with the nuclear envelope and of
      cytoplasmic double walled vesicles are reported. We suggest that these
      "electrondense spindle plaques" serve as foci for intranuclear and cytoplasmic
      microtubule arrangements, similar to the microtubule organizing centers within
      the centrosomes of animal cells. The extent to which the microsporidial division
      process is comparable with that of more familiar eukaryotes such as yeast cells
      is discussed.

PMID- 9627996
TI  - Insulin-like growth factor-I induces phosphorylation in Leishmania (Leishmania)
      mexicana promastigotes and amastigotes.
AB  - Protein phosphorylation controls major steps of proliferation and differentiation
      in eukaryotic cells. However there are few studies done in protozoa particularly
      when being triggered by external stimuli. In this paper we have examined the
      tyrosine- and serine/threonine-phosphorylated proteins in both promastigote and
      amastigote-like forms of Leishmania (Leishmania) mexicana stimulated with insulin
      like growth factor (IGF)-I. Stimulation with IGF-I induces major tyrosine
      phosphorylation of a 185-kDa protein in promastigotes and 60- and 40-kDa proteins
      in amastigotes. Analysis of total phosphorylation revealed additional sets of
      phosphorylated proteins: a 110-kDa protein band in promastigotes and two other
      proteins of 120 and 95 kDa in the amastigote-like forms. To further analyze the
      IGF-I-mediated response we compared it with the phosphorylation pattern obtained
      with a known inducer of protein kinase C, phorbol myristate acetate. This
      analysis showed overlapping phosphorylation of most of the proteins but mainly of
      the 185- and 110-kDa proteins in the promastigotes and the 95-, 60- and 40-kDa
      proteins in the amastigote-like forms. We thus conclude that there are
      phosphorylation-dependent pathways in Leishmania parasites induced by IGF-I that
      are stage-specific.

PMID- 9627997
TI  - Entamoeba histolytica contains a beta 1 integrin-like molecule similar to
      fibronectin receptors from eukaryotic cells.
AB  - Entamoeba histolytica trophozoites do interact with extracellular matrix
      components in order to invade and finally destroy tissue. An important step in
      this interaction involves the binding of a 140-kDa membrane protein that binds to
      fibronectin. The similarity of this amoebic receptor to fibronectin receptors
      from higher eukaryotic cells was defined by indirect immunofluorescence, western
      blot and immunohistochemistry, using polyclonal monospecific antibodies raised
      against the amoebic protein. These results suggest that lower eukaryotic cells
      have and use a beta 1 integrin-like molecule as well as mechanisms similar to
      those present in higher eukaryotic cells during interaction with extracellular
      matrix components.

PMID- 9627999
TI  - Nested clade analyses of phylogeographic data: testing hypotheses about gene flow
      and population history.
AB  - Since the 1920s, population geneticists have had measures that describe how
      genetic variation is distributed spatially within a species' geographical range.
      Modern genetic survey techniques frequently yield information on the evolutionary
      relationships among the alleles or haplotypes as well as information on allele
      frequencies and their spatial distributions. This evolutionary information is
      often expressed in the form of an estimated haplotype or allele tree. Traditional
      statistics of population structure, such as F statistics, do not make use of
      evolutionary genealogical information, so it is necessary to develop new
      statistical estimators and tests that explicitly incorporate information from the
      haplotype tree. One such technique is to use the haplotype tree to define a
      nested series of branches (clades), thereby allowing an evolutionary nested
      analysis of the spatial distribution of genetic variation. Such a nested analysis
      can be performed regarding the geographical sampling locations either as
      categorical or continuous variables (i.e. some measure of spatial distance). It
      is shown that such nested phylogeographical analyses have more power to detect
      geographical associations than traditional, nonhistorical analyses and, as a
      consequence, allow a broader range of gene-flow parameters to be estimated in a
      precise fashion. More importantly, such nested analyses can discriminate between
      phylogeographical associations due to recurrent but restricted gene flow vs.
      historical events operating at the population level (e.g. past fragmentation,
      colonization, or range expansion events). Restricted gene flow and historical
      events can be intertwined, and the cladistic analyses can reconstruct their
      temporal juxtapositions, thereby yielding great insight into both the
      evolutionary history and population structure of the species. Examples are given
      that illustrate these properties, concentrating on the detection of range
      expansion events.

PMID- 9628000
TI  - Comparative phylogeography and postglacial colonization routes in Europe.
AB  - The Quaternary cold periods in Europe are thought to have heavily influenced the
      amount and distribution of intraspecific genetic variation in both animals and
      plants. The phylogeographies of 10 taxa, including mammals (Ursus arctos, Sorex
      spp., Crocidura suaveolens, Arvicola spp.), amphibians (Triturus spp.),
      arthropods (Chorthippus parallelus), and plants (Abies alba, Picea abies, Fagus
      sylvatica, Quercus spp.), were analysed to elucidate general trends across
      Europe. Only a small degree of congruence was found amongst the phylogeographies
      of the 10 taxa, but the likely postglacial colonization routes exhibit some
      similarities. A Brooks parsimony analysis produced an unrooted area phylogram,
      showing that: (i) the northern regions were colonized generally from the Iberic
      and Balkanic refugia; and (ii) the Italian lineages were often isolated due to
      the presence of the Alpine barrier. The comparison of colonization routes
      highlighted four main suture-zones where lineages from the different refugia
      meet. Some of the intraspecific genetic distances among lineages indicated a
      prequaternary divergence that cannot be connected to any particular cold period,
      but are probably related mainly to the date of arrival of each taxon in the
      European continent. As a consequence, molecular genetics so far appears to be of
      limited use in dating Quaternary events.

PMID- 9628001
TI  - Molecular phylogeography and the evolution and conservation of Amazonian mammals.
AB  - The phylogeographic structure of 15 genera of Amazonian marsupials and rodents is
      summarized based on comparative sequence of the mitochondrial cytochrome b gene.
      The data are limited in geographical coverage, with samples widely scattered
      throughout Amazonia from the base of the Andes in Peru to the Guianan coast and
      eastern Brazil. We use this approach to define species boundaries, based
      minimally on the principle of reciprocal monophyly, in conjunction with
      morphological or other genetic discontinuities. The taxa so defined are older
      than previously appreciated, with many lineages dating from 1 to more than 3 Myr,
      and thus apparently predating the early Pleistocene. We relate patterns of
      concordant geographical shifts with underlying tectonic history and to current
      positions of major rivers. Finally, we provide comments on the utility of these
      data and patterns to conservation, articulating a need to incorporate
      phylogeographic information as part of the rationale in establishing conservation
      priorities at the organismal and geographical area levels.

PMID- 9628002
TI  - Comparative mtDNA phylogeography of neotropical freshwater fishes: testing shared
      history to infer the evolutionary landscape of lower Central America.
AB  - Historical biogeography seeks to explain contemporary distributions of taxa in
      the context of intrinsic biological and extrinsic geological and climatic
      factors. To decipher the relative importance of biological characteristics vs.
      environmental conditions, it is necessary to ask whether groups of taxa with
      similar distributions share the same history of diversification. Because all of
      the taxa will have shared the same climatic and geological history, evidence of
      shared history across multiple species provides an estimate of the role of
      extrinsic factors in shaping contemporary biogeographic patterns. Similarly,
      differences in the records of evolutionary history across species will probably
      be signatures of biological differences. In this study, we focus on inferring the
      evolutionary history for geographical populations and closely related species
      representing three genera of primary freshwater fishes that are widely
      distributed in lower Central America (LCA) and northwestern Colombia. Analysis of
      mitochondrial gene trees provides the opportunity for robust tests of shared
      history across taxa. Moreover, because mtDNA permits inference of the temporal
      scale of diversification we can test hypotheses regarding the chronological
      development of the Isthmian corridor linking North and South America. We have
      focused attention on two issues. First, we show that many of the distinct
      populations of LCA fishes diverged in a relatively brief period of time thus
      limiting the phylogenetic signal available for tests of shared history. Second,
      our results provide reduced evidence of shared history when all drainages are
      included in the analysis because of inferred dispersion events that obscure the
      evolutionary history among drainage basins. When we restrict the analysis to
      areas that harbour endemic mitochondrial lineages, there is evidence of shared
      history across taxa. We hypothesize that there were two to three distinct waves
      of invasion into LCA from putative source populations in northwestern Colombia.
      The first probably happened in the late Miocene, prior to the final emergence of
      the Isthmus in the mid-Pliocene; the second was probably coincident with the rise
      of the Isthmus in the mid-Pliocene, and the third event occurred more recently,
      perhaps in the Pleistocene. In each case the geographical scale of the dispersion
      of lineages was progressively more limited, a pattern we attribute to the
      continuing development of the landscape due to orogeny and the consequent
      increase in the insularization of drainage basins. Thus, the fisheye view of LCA
      suggests a complex biogeographic history of overlaid cycles of colonization,
      diversification, sorting and extinction of lineages.

PMID- 9628003
TI  - Speciation and phylogeography of Hawaiian terrestrial arthropods.
AB  - The Hawaiian archipelago is arguably the world's finest natural laboratory for
      the study of evolution and patterns of speciation. Arthropods comprise over 75%
      of the endemic biota of the Hawaiian Islands and a large proportion belongs to
      species radiations. We classify patterns of speciation within Hawaiian arthropod
      lineages into three categories: (i) single representatives of a lineage
      throughout the islands; (ii) species radiations with either (a) single endemic
      species on different volcanoes or islands, or (b) multiple species on each
      volcano or island; and (iii) single widespread species within a radiation of
      species that exhibits local endemism. A common pattern of phylogeography is that
      of repeated colonization of new island groups, such that lineages progress down
      the island chain, with the most ancestral groups (populations or species) on the
      oldest islands. While great dispersal ability and its subsequent loss are
      features of many of these taxa, there are a number of mechanisms that underlie
      diversification. These mechanisms may be genetic, including repeated founder
      events, hybridization, and sexual selection, or ecological, including shifts in
      habitat and/or host affiliation. The majority of studies reviewed suggest that
      natural selection is a primary force of change during the initial diversification
      of taxa.

PMID- 9628005
TI  - Molecular systematics of shrimp (Decapoda: Bresiliidae) from deep-sea
      hydrothermal vents, I: Enigmatic "small orange" shrimp from the Mid-Atlantic
      Ridge are juvenile Rimicaris exoculata.
AB  - Independent species descriptions of a "small orange" caridean shrimp found at
      deep-sea hydrothermal vents along the Mid-Atlantic Ridge have created the
      synonymous names Iorania concordia Vereshchaka 1996b and Rimicaris aurantiaca
      Martin et al. 1997. Our genetic analyses involving allozymes and mitochondrial
      DNA sequences reveal that the "small orange" shrimp described in these studies
      are a juvenile form of Rimicaris exoculata Williams and Rona, a species commonly
      found at these sites. In light of this result, we reconsider the life history and
      ecologic characteristics of juvenile and adult stages of Rimicaris exoculata.

PMID- 9628006
TI  - Purification and characterization of pancreatic elastase from North Atlantic
      salmon (Salmo salar).
AB  - An elastase I-like enzyme was purified to homogeneity from the pyloric caeca of
      North Atlantic salmon (Salmo salar) and compared with porcine elastase I. The
      molecular weight and isoelectric point were estimated to be 27 kDa and over 9.3,
      respectively. The pH optimum was between 8.0 and 9.5, and the enzyme was unstable
      at pH values below 4. Kinetic properties examined using Suc-(Ala)3-p-nitroanilide
      showed that the catalytic efficiency of salmon elastase was about 2.5 times
      higher than that of porcine elastase. Furthermore, the salmon enzyme was less
      stable at lower pH values and temperatures than the porcine enzyme. The
      preference for amino acids at the primary binding site was found to be different
      from that of the porcine elastase. The salmon elastase binding pocket seems to
      prefer more branched aliphatic residues than the porcine elastase.

PMID- 9628004
TI  - Evolution on a volcanic conveyor belt: using phylogeographic reconstructions and
      K-Ar-based ages of the Hawaiian Islands to estimate molecular evolutionary rates.
AB  - The Hawaiian Islands form as the Pacific Plate moves over a 'hot spot' in the
      earth's mantle where magma extrudes through the crust to build huge shield
      volcanos. The islands subside and erode as the plate carries them to the north
      west, eventually to become coral atolls and seamounts. Thus islands are ordered
      linearly by age, with the oldest islands in the north-west (e.g. Kauai at 5.1 Ma)
      and the youngest in the south-east (e.g. Hawaii at 0.43 Ma). K-Ar estimates of
      the date of an island's formation provide a maximum age for the taxa inhabiting
      the island. These ages can be used to calibrate rates of molecular change under
      the following assumptions: (i) K-Ar dates are accurate; (ii) tree topologies show
      that derivation of taxa parallels the timing of island formation; (iii)
      populations do not colonize long after island emergence; (iv) the coalescent
      point for sister taxa does not greatly predate the formation of the colonized
      younger island; (v) saturation effects and (vi) among-lineage rate variation are
      minimal or correctable; and (vii) unbiased standard errors of distances and
      regressions can be estimated from multiple pairwise comparisons. We use the
      approach to obtain overall corrected rate calibrations for: (i) part of the
      mitochondrial cytochrome b gene in Hawaiian drepanidines (0.016 sequence
      divergence/Myr); (ii) the Yp1 gene in Hawaiian Drosophila (0.019/Myr Kambysellis
      et al. 1995); and (iii) parts of the mitochondrial 12S and 16S rRNA and tRNAval
      in Laupala crickets (0.024-0.102/Myr, Shaw 1996). We discuss the reliability of
      the estimates given the assumptions (i-vii) above and contrast the results with
      previous calibrations of Adh in Hawaiian Drosophila and chloroplast DNA in
      lobeliods.

PMID- 9628007
TI  - Yeasts isolated from the intestine of rainbow trout adhere to and grow in
      intestinal mucus.
AB  - The yeast strains Saccharomyces cerevisiae CBS 7764 and Debaryomyces hansenii Hf1
      (CBS 8339), isolated from the intestine of rainbow trout, were studied with
      respect to adhesion to and growth in fish intestinal mucus. The level of adhesion
      was dependent on the physiologic state of the yeast culture. Growing cells of
      both strains adhered more strongly than nongrowing cells. This correlates with a
      previously shown shift in cell surface hydrophobicity of these yeasts. In
      addition, forces other than hydrophobic interactions may participate, as all
      strains tested adhered more strongly to the membrane lipid phosphatidylserine
      than to phosphatidylcholine and phosphatidylethanolamine. Debaryomyces hansenii
      Hf1 also adhered to the most hydrophobic of the neutral lipids present in mucus,
      while no adhesion was observed to the other neutral lipids or to the hydrophilic
      silica gel, again suggesting hydrophobic interactions. Finally, the fish-isolated
      yeasts grew rapidly in isolated fish intestinal mucus as the sole source of
      energy and nutrients.

PMID- 9628008
TI  - A DNA probe for identification of larvae of the commercial surfclam (Spisula
      solidissima).
AB  - A molecular DNA probe was developed for identification of larvae of the
      commercial surfclam Spisula solidissima (family Mactridae), to distinguish early
      stage veligers from larvae of other common bivalve species in a study of surfclam
      settlement and recruitment on the New Jersey continental shelf. For
      discrimination of S. solidissima from other common bivalve species at the study
      site (almost all of which belong to different families), an oligonucleotide
      designed from the nucleotide sequence of the 18S ribosomal RNA gene provides a
      useful and sensitive family-specific probe and primer. For discrimination between
      S. solidissima and Mulinia lateralis (both members of Mactridae), the 18S rRNA
      gene was examined by restriction fragment length polymorphism (RFLP) analysis. A
      combination of the DNA probe and RFLP analysis provides a positive identification
      of S. solidissima and M. lateralis larvae in coastal plankton samples.

PMID- 9628009
TI  - Molecular cloning of a novel interferon regulatory factor in Japanese flounder,
      Paralichthys olivaceus.
AB  - A complementary DNA library was constructed in lambda ZAP II using messenger RNA
      from the leukocytes of some heterocloned Japanese flounder, Paralichthys
      olivaceus, that had been artificially infected with Hirame rhabdovirus (HRV). A
      cloned flounder interferon regulatory factor (designated fIRF) cDNA was found to
      be 1746 bp in length, with an open reading frame of 297 amino acids. The overall
      amino acid sequence of fIRF had approximately 40% identity with the previously
      reported avian and mammalian IRF-1s and IRF-2s. The fIRF sequence was most
      similar to that recorded for the chicken IRF-1. Amino acid sequence identities
      between the DNA-binding domain of the fIRF and that of both chicken IRF-1 and
      chicken IRF-2 were 72.3%. The DNA-binding domain of fIRF contained the repeated
      tryptophan motif that is characteristic of members of the IRF family. The mRNA of
      fIRF was detected in various tissues by reverse transcription-polymerase chain
      reaction (RT-PCR). The fIRF was transcribed mainly in the intestine, ovary,
      muscle, liver, heart and spleen, while it was minimally transcribed in the brain
      and kidney. When Japanese flounder were injected with HRV, the relative
      expression of fIRF mRNA was found to increase and peak 3 days after injection.
      The quantities of the fIRF mRNA increased to levels that were 7.5-fold higher
      than those of noninjected fish. In addition, when Japanese flounder were injected
      with Edwardsiella tarda, the expression of fIRF mRNA showed increases 2, 3, and 4
      days after injection. The quantities of the fIRF mRNA on those days represented
      approximately 6-, 15-, and 14-fold increases, respectively, over the levels in
      noninjected fish.

PMID- 9628010
TI  - A monophyletic origin of heart-predominant lactate dehydrogenase (LDH) isozymes
      of gnathostome vertebrates: evidence from the cDNA sequence of the spiny dogfish
      (Squalus acanthias) LDH-B.
AB  - Duplication of a single lactate dehydrogenase locus early in vertebrate evolution
      has been proposed to have given rise to Ldh-A and Ldh-B, the encoded isozymes of
      which predominate in skeletal and heart muscle, respectively. This view has been
      challenged recently by phylogenetic analyses of LDH sequences. One question that
      has been raised is whether the heart-predominant isozyme (LDH-B) of cartilaginous
      fishes is orthologous to that of bony fishes and their derivatives. To address
      this issue, we determined the complementary DNA sequence of the LDH-B of the
      chondrichthyan Squalus acanthias. Phylogenetic analysis of this and other LDH
      isozyme sequences provided strong support for a single origin of LDH-Bs prior to
      the divergence of cartilaginous and bony fishes.

PMID- 9628011
TI  - Sensing trehalose biosynthesis in plants.
AB  - A most unexpected finding in research on plant carbohydrate metabolism is the
      recent discovery that angiosperms encode genes whose products are involved in
      trehalose metabolism. The presence and functionality of such genes has been
      elegantly shown by expressing Arabidopsis-derived trehalose phosphate synthase
      and trehalose phosphate phosphatase genes in yeast mutants lacking these
      enzymatic activities. Homologue sequences have now been cloned from a number of
      different plant species suggesting that the capacity to synthesise trehalose is
      ubiquitous in angiosperms. Except for Myrothamnus flabellifolius, trehalose
      biosynthesis has never been observed in tissues of higher plants, probably due to
      the presence of high levels of trehalase activity. The function of trehalose
      metabolism in plants is still a mystery. One of the postulated functions of
      trehalose metabolism in yeast is in the control of glucose repression and a
      similar function in sugar sensing can be proposed for plants as well.

PMID- 9628012
TI  - A moderate decrease of plastid aldolase activity inhibits photosynthesis, alters
      the levels of sugars and starch, and inhibits growth of potato plants.
AB  - Antisense expression of a full length cDNA encoding plastid aldolase led to
      decreased expression of aldolase at the transcript and protein level in several
      'antisense' potato transformants. To quantify the inhibition, activity was
      compared in corresponding leaves down a plant and in plants of different ages.
      Aldolase activity was decreased by 32-43%, 56-71%, 79-83% and 91-97% in A-70, A
      3, A-51 and A-2. Separation on a Q-Sepharose-FF column showed the decrease was
      due to inhibition of plastid aldolase. The transformants showed a small increase
      of Rubisco activity, a small decrease of phosphoribulokinase activity, and larger
      but subproportional decreases of sedoheptulose-1,7-biphosphatase and plastid
      fructose-1,6-bisphosphatase activity. Ambient photosynthesis was inhibited by
      10%, 40%, 66% and 85% in A-70, A-3, A-51 and A-2. The transformants contained
      increased triose phosphates, and very low ribulose-1,5-bisphosphate and glycerate
      3-phosphate. Chlorophyll fluorescence indicated that photosystem II was more
      reduced and thylakoid energization was increased. Starch synthesis was decreased
      by 16% and 36% in A-70 and A-3, whereas sucrose synthesis was less strongly
      inhibited. Plant growth was not significantly altered in A-70, was decreased by
      41% in A-3, and was severely inhibited in plants with under 20% of wild-type
      aldolase activity. Although plastid aldolase catalyses a readily reversible
      reaction, possesses no known regulatory properties, and would appear irrelevant
      for the control of metabolism and growth, small changes in its activity have
      marked consequences for photosynthesis, carbon partitioning and growth.

PMID- 9628013
TI  - N- and C-terminal peptide sequences are essential for enzyme assembly,
      allosteric, and/or catalytic properties of ADP-glucose pyrophosphorylase.
AB  - ADP-glucose pyrophosphorylase is a key regulatory enzyme in starch synthesis in
      most plant tissues. Unlike the allosteric regulatory dependent properties of the
      leaf enzyme, the enzymes from non-photosynthetic tissues exhibit varying levels
      of sensitivity to allosteric regulation, a behavior which may be an inherent
      property of the enzyme or a product of post-translational modification. As
      partial proteolysis of the holoenzyme may account for the wide variation of
      allosteric regulatory behavior exhibited by enzymes from non-photosynthetic
      tissues, small N- and C-terminal peptide deletions were made on either the potato
      large and small subunit and co-expressed with the counterpart wild-type subunit
      in Escherichia coli. Removal of the putative carboxy-terminal allosteric binding
      region from either subunit type results in an abolishment of enzyme formation
      indicating that the carboxy terminus of each subunit type is essential for proper
      subunit folding and/or enzyme assembly as well as its suggested role in
      allosteric regulation. Removal of a small 10 amino acid peptide from the N
      terminus of the small subunit increased its resistance to the allosteric
      inhibitor Pi as well as its sensitivity to heat treatment. Likewise, removal of
      the corresponding peptide (17 residues) at the N-terminus of the large subunit
      also increased its resistance towards Pi inhibition but, in addition, increased
      its sensitivity to 3-PGA activation. Deletion of an additional 11 residues
      reversed these changes in allosteric properties but at the expense of a reduced
      catalytic turnover rate. Combined, these results indicate that the N- and C
      terminal regions are essential for the proper catalytic and allosteric regulatory
      properties of the potato ADP-glucose pyrophosphorylase. The possible significance
      of these results on the observed insensitivity to effector molecules by ADP
      glucose pyrophosphorylases from other non-photosynthetic tissues is discussed.

PMID- 9628014
TI  - 5'- and 3'-sequences of satellite tobacco necrosis virus RNA promoting
      translation in tobacco.
AB  - The RNA of satellite tobacco necrosis virus (STNV) is a monocistronic messenger
      that lacks both a 5' cap and a 3' poly(A) tail. The STNV trailer contains an
      autonomous translational enhancer domain (TED) that promotes translation in vitro
      by more than one order of magnitude when combined with the 5'-terminal 173 nt of
      STNV RNA. We now show that the responsible sequence within the 5' region maps to
      the first 38 nt of the STNV RNA. Mutational analysis indicated that the primary
      sequence of the STNV 5' 38 nt and TED is important for translation stimulation in
      vitro, but did not reveal a role for the complementarity between the two.
      Translation of chimeric STNV-cat RNAs in tobacco protoplasts showed that TED
      promotes translation in vivo of RNAs lacking a cap and/or a poly(A) tail. Similar
      to in vitro, TED-dependent translation in tobacco was stimulated further by the
      STNV 5' 38 nt.

PMID- 9628015
TI  - Identification and characterization of a locus (RTM1) that restricts long
      distance movement of tobacco etch virus in Arabidopsis thaliana.
AB  - Screens of Arabidopsis thaliana for susceptibility to tobacco etch virus (TEV)
      revealed that each of 10 ecotypes were able to support genome replication and
      cell-to-cell movement in inoculated leaves. However, only four ecotypes,
      including C24 and La-er, supported complete infections in which TEV was able to
      replicate and move from cell to cell and long distances through the vasculature.
      The rates of cell-to-cell movement of a reporter-tagged TEV strain (TEV-GUS) in
      inoculated leaves of C24 and Columbia (Col-3) were similar, and infection foci
      continued to expand in both ecotypes through 10 days post-inoculation. No visible
      or microscopic hypersensitive or cell death responses were evident in inoculated
      leaves of Col-3 plants. Infection of neither C24 nor Col-3 plants with TEV-GUS
      resulted in induction of PR-1a gene expression, which is normally associated with
      active defence responses and systemic acquired resistance. The genetic basis for
      the restriction of long-distance movement of TEV-GUS in Columbia was investigated
      using C24 x Col-3 crosses and backcrosses and using La-er x Col-0 recombinant
      inbred lines. A dominant locus conditioning the restricted TEV infection
      phenotype was identified on chromosome 1 between markers ATEAT1 and NCC1 at
      approximately 14 cM in both genetic analyses. This locus was designated RTM1
      (restricted TEV movement 1). It is proposed that RTM1 mediates a restriction of
      long-distance movement through a mechanism that differs substantially from those
      conditioned by the dominant resistance genes normally associated with gene-for
      gene interactions.

PMID- 9628017
TI  - Cloning and functional expression of AtCOQ3, the Arabidopsis homologue of the
      yeast COQ3 gene, encoding a methyltransferase from plant mitochondria involved in
      ubiquinone biosynthesis.
AB  - A mutant of Saccharomyces cerevisiae deleted for the COQ3 gene was constructed.
      COQ3 encodes a 3,4-dihydroxy-5-hexaprenylbenzoate (DHHB) methyltransferase that
      catalyses the fourth step in the biosynthesis of ubiquinone from p-hydroxybenzoic
      acid. A full length cDNA encoding a homologue of DHHB-methyltransferase was
      cloned from an Arabidopsis thaliana cDNA library by functional complementation of
      a yeast coq3 deletion mutant. The Arabidopsis thaliana cDNA (AtCOQ3) was able to
      restore the respiration ability and ubiquinone synthesis of the mutant. The
      product of the 1372 bp cDNA contained 322 amino acids and had a molecular mass of
      35,360 Da. The predicted amino acid sequence contained all consensus regions for
      S-adenosyl methionine methyltransferases and presented 26% identity with
      Saccharomyces cerevisiae DHHB-methyltransferase and 38% identity with the rat
      protein, as well as with a bacterial (Escherichia coli and Salmonella
      typhimurium) methyltransferase encoded by the UBIG gene. Southern analysis showed
      that the Arabidopsis thaliana enzyme was encoded by a single nuclear gene. The
      NH2-terminal part of the cDNA product contained features consistent with a
      putative mitochondrial transit sequence. The cDNA in Escherichia coli was
      overexpressed and antibodies were raised against the recombinant protein. Western
      blot analysis of Arabidopsis thaliana and pea protein extracts indicated that the
      AtCOQ3 gene product is localized within mitochondrial membranes. This result
      suggests that at least this step of ubiquinone synthesis takes place in
      mitochondria.

PMID- 9628018
TI  - Substrate specificities of tobacco chitinases.
AB  - Ten tobacco chitinases (1,4-N-acetyl-beta-D-glucosaminide glycanhydrolase, EC
      3.2.1.14) were purified from tobacco leaves hypersensitively reacting to tobacco
      mosaic virus. The 10 enzymes, which belong to five distinct structural classes of
      plant chitinases, were incubated with several potential substrates such as
      chitin, a beta-1,4 N-acetyl-D-glucosamine (GlcNAc) polymer, chitosan (partially
      deacetylated chitin), chitin oligomers of variable length and bacterial cell
      wall. Tobacco chitinases are all endotype enzymes that liberate oligomers from
      chitin and are capable of processing the chito-oligomers further at differential
      rates. Chitin reaction products were separated and quantified by HPLC and
      differential kinetics of oligomer accumulation and degradation were observed with
      the distinct classes of chitinases. Depending on the substrate to be hydrolysed,
      each isoform displayed a different spectrum of activity. For example, class I
      isoforms were the most active on chitin and (GlcNAc)4-6 whereas class III basic
      isoforms were the most efficient in inducing bacterial lysis. Class V and class
      VI chitinases were shown to more readily hydrolyse chitin oligomers than the
      chitin polymer itself. Together, these data indicate that the 10 tobacco
      chitinases represent complementary enzymes which may have synergistic effects on
      their substrates. This paper discusses their implication in plant defense by
      attacking pathogen's structural components and in plant development by maturing
      signal molecules.

PMID- 9628019
TI  - Transcription pattern of a FIM homologue in Impatiens during floral development
      and reversion.
AB  - Flowering and reversion in Impatiens are characterised by gradual transitions of
      organ identity and constitute a unique system for the molecular and physiological
      study of floral organogenesis. The authors have isolated an Impatiens homologue
      of the FIM gene of Antirrhinum (UFO in Arabidopsis), Imp-FIM, and analysed its
      expression in three states of the terminal meristem: vegetative, floral, and
      reverted. In floral meristems, Imp-FIM transcription is associated with petal
      identity, as in Antirrhinum and Arabidopsis, but this is achieved through a novel
      transcription pattern, characterised by a high level of transcript within petal
      primordia. This novel transcription pattern could contribute to the more diffuse
      boundaries between organ types in Impatiens. In vegetative meristems, Imp-FIM is
      expressed in the axils of leaf primordia which are arranged in a spiral. A
      similar pattern is observed in reverted meristems in which leaf primordia are
      initiated in a whorled arrangement. This result indicates that the maintenance of
      floral phyllotaxis is not associated with a specific pattern of Imp-FIM
      transcription. Transcription of Imp-FIM in a non-reverting line is no different
      from that in the reverting line. Therefore, the lack of floral commitment in the
      reverting line does not seem to be responsible for Imp-FIM transcription within
      petals. The novel transcription pattern in petals, together with features of
      Impatiens that are reminiscent of fim and ufo mutant phenotypes suggest an
      evolutionary divergence for Imp-FIM regulation in this species.

PMID- 9628020
TI  - Glucocorticoid-inducible expression of a bacterial avirulence gene in transgenic
      Arabidopsis induces hypersensitive cell death.
AB  - Pathogenic strains of Pseudomonas syringae pv. tomato carrying the avrRpt2
      avirulence gene specifically induce a hypersensitive cell death response in
      Arabidopsis plants that contain the complementary RPS2 disease resistance gene.
      Transient expression of avrRpt2 in Arabidopsis plants having the RPS2 gene has
      been shown to induce hypersensitive cell death. In order to analyze the effects
      of conditional expression of avrRpt2 in Arabidopsis plants, transgenic lines were
      constructed that contained the avrRpt2 gene under the control of a tightly
      regulated, glucocorticoid-inducible promoter. Dexamethasone-induced expression of
      avrRpt2 in transgenic lines having the RPS2 gene resulted in a specific
      hypersensitive cell death response that resembled a Pseudomonas syringae-induced
      hypersensitive response and also induced the expression of a pathogenesis-related
      gene (PR1). Interestingly, high level expression of avrRpt2 in a mutant rps2-101C
      background resulted in plant stress and ultimately cell death, suggesting a
      possible role for avrRpt2 in Pseudomonas syringae virulence. Transgenic RPS2 and
      rps2 plants that contain the glucocorticoid-inducible avrRpt2 gene will provide a
      powerful new tool for the genetic, physiological, biochemical, and molecular
      dissection of an avirulence gene-specified cell death response in both resistant
      and susceptible plants.

PMID- 9628021
TI  - Development of an AFLP based linkage map of Ler, Col and Cvi Arabidopsis thaliana
      ecotypes and construction of a Ler/Cvi recombinant inbred line population.
AB  - An amplified fragment polymorphism (AFLP) based linkage map has been generated
      for a new Landsberg erecta/ Cape Verde Islands (Ler/Cvi) recombinant inbred line
      (RIL) population. A total of 321 molecular PCR based markers and the erecta
      mutation were mapped. AFLP markers were also analysed in the Landsberg
      erecta/Columbia (Ler/Col) RIL population (Lister and Dean, 1993) and 395 AFLP
      markers have been integrated into the previous Arabidopsis molecular map of 122
      RFLPs, CAPSs and SSLPs. This enabled the evaluation of the efficiency and
      robustness of AFLP technology for linkage analyses in Arabidopsis. AFLP markers
      were found throughout the linkage map. The two RIL maps could be integrated
      through 49 common markers which all mapped at similar positions. Comparison of
      both maps led to the conclusion that segregating bands from a common parent can
      be compared between different populations, and that AFLP bands of similar
      molecular size, amplified with the same primer combination in two different
      ecotypes, are likely to correspond to the same locus. AFLPs were found clustering
      around the centromeric regions, and the authors have established the map position
      of the centromere of chromosome 3 by a quantitative analysis of AFLP bands using
      trisomic plants. AFLP markers were also used to estimate the polymorphism rate
      among the three ecotypes. The larger polymorphism rate found between Ler and Cvi
      compared to Ler and Col will mean that the new RIL population will provide a
      useful material to map DNA polymorphisms and quantitative trait loci.

PMID- 9628022
TI  - More than 80R2R3-MYB regulatory genes in the genome of Arabidopsis thaliana.
AB  - Transcription factors belonging to the R2R3-MYB family contain the related helix
      turn-helix repeats R2 and R3. The authors isolated partial cDNA and/or genomic
      clones of 78 R2R3-MYB genes from Arabidopsis thaliana and found accessions
      corresponding to 31 Arabidopsis genes of this class in databanks, seven of which
      were not represented in the authors' collection. Therefore, there are at least
      85, and probably more than 100, R2R3-MYB genes present in the Arabidopsis
      thaliana genome, representing the largest regulatory gene family currently known
      in plants. In contrast, no more than three R2R3-MYB genes have been reported in
      any organism from other phyla. DNA-binding studies showed that there are
      differences but also frequent overlaps in binding specificity among plant R2R3
      MYB proteins, in line with the distinct but often related functions that are
      beginning to be recognized for these proteins. This large-sized gene family may
      contribute to the regulatory flexibility underlying the developmental and
      metabolic plasticity displayed by plants.

PMID- 9628023
TI  - Systemic and local induction of an Arabidopsis thionin gene by wounding and
      pathogens.
AB  - The Arabidopsis Thi2.1 thionin gene was cloned and sequenced. The promoter was
      fused to the uidA gene and stably transformed into Arabidopsis to study its
      regulation. GUS expression levels correlated with the steady-state levels of
      Thi2.1 mRNA, thus demonstrating that the promoter is sufficient for the
      regulation of the Thi2.1 gene. The sensitivity of the Thi2.1 gene to methyl
      jasmonate was found to be developmentally determined. Systemic and local
      expression could be induced by wounding and inoculation with Fusarium oxysporum f
      sp. matthiolae. A deletion analysis of the promoter identified a fragment of 325
      bp upstream of the start codon, which appears to contain all the elements
      necessary for the regulation of the Thi2.1 gene. These results support the view
      that thionins are defence proteins, and indicate the possibility that resistance
      of Arabidopsis plants to necrotrophic fungal pathogens is mediated through the
      octadecanoid pathway.

PMID- 9628024
TI  - Acetyl-CoA:benzylalcohol acetyltransferase--an enzyme involved in floral scent
      production in Clarkia breweri.
AB  - Volatile esters impart distinct characteristics to the floral scent of many
      plants, and are important in attracting insect pollinators. They are also
      important flavor compounds in fruits. The ester benzylacetate is a major
      constituent of the floral scent of Clarkia breweri, an annual plant native to
      California. The enzyme acetyl-CoA:benzylalcohol acetyltransferase (BEAT), which
      catalyzes the formation of benzylacetate, has been purified from C. breweri
      petals, and a cDNA encoding this enzyme has been isolated and characterized. The
      sequence of the 433-residue BEAT protein does not show high similarity to any
      previously characterized protein, but a 35-residue region from position 135-163
      has significant similarity (42-56% identity) to several proteins known or
      suspected to use an acyl-CoA substrate. E. coli cells expressing C. breweri BEAT
      produced enzymatically active protein, and also synthesized benzylacetate and
      secreted it into the medium. Of the different parts of the C. breweri flower,
      petals contained the majority of BEAT transcripts, and no BEAT mRNA was detected
      in leaves. The levels of BEAT mRNA in the petals increased as the bud matured,
      and peaked at anthesis, paralleling changes in BEAT activity. However, three days
      after anthesis, mRNA levels began a steep decline, whereas BEAT activity remained
      high for the next two days, suggesting that the BEAT protein is relatively
      stable.

PMID- 9628025
TI  - Functional integration of non-native carotenoids into chloroplasts by viral
      derived expression of capsanthin-capsorubin synthase in Nicotiana benthamiana.
AB  - The biosynthesis of leaf carotenoids in Nicotiana benthamiana was altered by
      forced re-routing of the pathway to the synthesis of capsanthin, a non-native
      chromoplast-specific xanthophyll, using an RNA viral vector containing capsanthin
      capsorubin synthase (Ccs) cDNA. The cDNA encoding Ccs was placed under the
      transcriptional control of a tobamovirus subgenomic promoter. Leaves from
      transfected plants expressing Ccs developed an orange phenotype and accumulated
      high levels of capsanthin (up to 36% of total carotenoids). This phenomenon was
      associated with thylakoid membrane distortion and reduction of grana stacking. In
      contrast to the situation prevailing in chromoplasts, capsanthin was not
      esterified and its increased level was balanced by a concomitant decrease of the
      major leaf xanthophylls, suggesting an autoregulatory control of chloroplast
      carotenoid composition. Capsanthin was exclusively recruited into the trimeric
      and monomeric light-harvesting complexes of photosystem II (PSII) and shown to
      significantly contribute to the light-harvesting capacity. On a chlorophyll
      basis, the concentrations of PSI and PSII reaction centres were not modified.
      This demonstration that higher plant antenna complexes can accommodate non-native
      carotenoids provides compelling evidence for functional remodelling of
      photosynthetic membranes toward a better photoreactivity by rational design of
      the incorporated carotenoid structures.

PMID- 9628026
TI  - A response-regulator homologue possibly involved in nitrogen signal transduction
      mediated by cytokinin in maize.
AB  - A cDNA clone, pZmCip1, encoding a maize (Zea mays) cytokinin-inducible protein 1
      was isolated utilizing the differential display technique, and studied using the
      expression of ZmCip1 in nitrogen-starved maize plants. The cloned cDNA contained
      an open reading frame consisting of 157 amino acids with a predicted molecular
      mass of 16.7 kDa, which possesses similarity with the response-regulators of
      bacterial two-component signalling systems. In detached leaves, accumulation of
      ZmCip1 transcript by t-zeatin was dose-dependent in a range of 10(-9) M to 10(-7)
      M, and occurred within 30 min after treatment. The effect of t-zeatin was
      replaceable by isopentenyl-adenosine or isopentenyl-adenosine-5'-monophosphate.
      Pretreatment of detached leaves with cycloheximide did not inhibit the
      accumulation of the transcript. In whole plants, ZmCip1 transcript was
      transiently accumulated exclusively in leaves by supply of nitrate or ammonium
      ions to the roots, whereas the transcript was not accumulated in detached leaves
      by supply of the nitrogen nutrients. Both the cytokinin- and nitrate-responsive
      accumulations of ZmCip1 transcript were accompanied by an increase in the
      immunotitratable protein. Isopentenyladenosine and/or its phosphorylated form(s)
      accumulated in roots 2 h after supply of nitrate to plants. These results, taken
      together, suggest that ZmCip1 is a primary response gene to cytokinins, and that
      it involves, at least in part, the nitrogen-signal transduction mediated by
      cytokinin in maize.

PMID- 9628027
TI  - Targeting and modification of prokaryotic cell-cell junctions by tobacco mosaic
      virus cell-to-cell movement protein.
AB  - The movement protein (MP) of tobacco mosaic virus (TMV) facilitates the cell-to
      cell spread of infection by altering the structure and function of plasmodesmata,
      the intercellular communication channels in plants. Because the protein was shown
      to interfere with intercellular communication when expressed in the
      cyanobacterium Anabaena sp. strain PCC 7120, whether the ability of the protein
      to target and to modify intercellular communication channels in plants is
      conserved in this prokaryote was investigated. It was found that the MP localizes
      to the cell junctions and induces the formation of filamentous structures that
      traverse the septa. It is proposed that the protein interacts with host
      components that are similar between plants and Anabaena and that may be
      evolutionarily related. The observations in Anabaena suggest that the MP modifies
      plasmodesmata by forming a filamentous aggregate within the pore.

PMID- 9628029
TI  - Magnesium ions promote assembly of channel-like structures from beticolin 0, a
      non-peptide fungal toxin purified from Cercospora beticola.
AB  - Beticolins are toxins produced by the fungus Cercospora beticola. Using beticolin
      0 (B0), we have produced a strong and Mg(2+)-dependent increase in the membrane
      conductance of Arabidopsis protoplasts and Xenopus oocytes. In protein-free
      artificial bilayers, discrete deflexions of current were observed (12 pS unitary
      conductance in symmetrical 100 mM KCl) in the presence of B0 (approximately 10
      microM) and in the presence of nominal Mg2+. Addition of 50 microM Mg2+ induced a
      macroscopic current which could be reversed to single channel current by
      chelating Mg2+ with EDTA. Both unitary and macroscopic currents were ohmic. The
      increase in conductance of biological membranes triggered by B0 is therefore
      likely to originate from the ability of this toxin to organize itself into
      transmembrane pores in the presence of Mg2+. The pore is poorly selective,
      displaying permeability ratios PCl/PK, PNa/PK and PCa/PK close to 0.3, 0.65 and
      0.4, respectively. Such channel-like activity could be involved in the
      deleterious biological activity of the toxin, by causing the collapse of ionic
      and electrical gradients through biological membranes together with Ca2+ influx
      and scrambling of cellular signals.

PMID- 9628030
TI  - Six Arabidopsis thaliana homologues of the human respiratory burst oxidase
      (gp91phox).
AB  - An NADPH oxidase analogous to that in mammalian phagocytes has been hypothesized
      to produce reactive oxygen species (ROS) in the plant defence response. A.
      thaliana contains at least six gp91phox homologues, designated AtrbohA-F (A.
      thaliana Respiratory Burst Oxidase Homologues), which map to different positions.
      Transcripts of three of these genes can be detected in healthy plants by RNA gel
      blot analyses. The Atrboh gene products are closely related to gp91phox and the
      intron locations suggest a common evolutionary origin. A putative EF-hand Ca(2+)
      binding motif in the extended N-terminal region of the Atrboh proteins suggests a
      direct regulatory effect of Ca2+ on the activity of the NADPH oxidase in plants.

PMID- 9628031
TI  - Phage display selection can differentiate insecticidal activity of soybean
      cystatins.
AB  - Plant cysteine proteinase inhibitors (phytocystatins) have been implicated as
      defensive molecules against Coleopteran and Hemipteran insect pests. Two soybean
      cystatins, soyacystatin N (scN) and soyacystatin L (scL), have 70% sequence
      identity but scN is a much more potent inhibitor of papain, vicilin
      peptidohydrolase and insect gut proteinases. When these cystatins were displayed
      on phage particles, papain-binding affinity and CPI activity of scN were
      substantially greater than those of scL, in direct correlation with their
      relative CPI activity as soluble recombinant proteins. Furthermore, scN
      substantially delayed cowpea weevil (Callosobruchus maculatus (F.)) growth and
      development in insect feeding bioassays, whereas scL was essentially inactive as
      an insecticide. Papain biopanning selection of phage-displayed soyacystatins
      resulted in a 200-1000-fold greater enrichment for scN relative to scL. These
      results establish that binding affinity of cystatins can be used in phage display
      biopanning procedures to select variants with greater insecticidal activity,
      illustrating the potential of phage display and biopanning selection for directed
      molecular evolution of biological activity of these plant defensive proteins.

PMID- 9628032
TI  - A robust method for detecting single-nucleotide changes as polymorphic markers by
      PCR.
AB  - Numerous techniques in plant molecular genetic analysis, such as mapping and
      positional cloning techniques, rely on the availability of molecular markers that
      can differentiate between alleles at a particular locus. PCR-based cleaved
      amplified polymorphic sequences (CAPS) markers have been widely used as a means
      of rapidly and reliably detecting a single-base change that creates a unique
      restriction site in one of a pair of alleles. However, the majority of single
      nucleotide changes do not create such sites and thus cannot be used to create
      CAPS markers. In this paper, a modification of the CAPS technique that allows
      detection of most single-nucleotide changes by utilizing mismatched PCR primers
      is described. The mismatches in the PCR primers, in combination with the single
      nucleotide change, create a unique restriction site in one of the alleles.

PMID- 9628033
TI  - dCAPS, a simple technique for the genetic analysis of single nucleotide
      polymorphisms: experimental applications in Arabidopsis thaliana genetics.
AB  - PCR-based detection of single nucleotide polymorphisms is a powerful tool for the
      plant geneticist. Cleaved amplified polymorphic sequence analysis is the most
      widely used approach for the detection of single nucleotide polymorphisms.
      However, this technique is limited to mutations which create or disrupt a
      restriction enzyme recognition site. This paper presents a modification of this
      technique where mismatches in a PCR primer are used to create a polymorphism
      based on the target mutation. This technique is useful for following known
      mutations in segregating populations and genetic mapping of isolated DNAs used
      for positional based cloning of new genes. In addition, a computer program has
      been developed that facilitates the design of these PCR primers.

PMID- 9628034
TI  - Patterns of density dependence in measles dynamics.
AB  - An important question in metapopulation dynamics is the influence of external
      perturbations on the population's long-term dynamic behaviour. In this paper we
      address the question of how spatiotemporal variations in demographic parameters
      affect the dynamics of measles populations in England and Wales. Specifically, we
      use nonparametric statistical methods to analyse how birth rate and population
      size modulate the negative density dependence between successive epidemics as
      well as their periodicity. For the observed spatiotemporal data from 60 cities,
      and for simulated model data, the demographic variables act as bifurcation
      parameters on the joint density of the trade-off between successive epidemics.
      For increasing population size, a transition occurs from an irregular
      unpredictable pattern in small communities towards a regular, predictable endemic
      pattern in large places. Variations in the birth rate parameter lead to a
      bifurcation from annual towards biennial cyclicity in both observed data and
      model data.

PMID- 9628035
TI  - The malaria parasite, Plasmodium falciparum, increases the frequency of multiple
      feeding of its mosquito vector, Anopheles gambiae.
AB  - It has often been suggested that vector-borne parasites alter their vector's
      feeding behaviour to increase their transmission, but these claims are often
      based on laboratory studies and lack rigorous testing in a natural situation. We
      show in this field study that the malaria parasite, Plasmodium falciparum, alters
      the blood-feeding behaviour of its mosquito vector, Anopheles gambiae s.l., in
      two ways. First, mosquitoes infected with sporozoited, the parasite stage that is
      transmitted from the mosquito to a human, took up larger blood meals than
      uninfected mosquitoes. Whereas 72% of the uninfected mosquitoes had obtained a
      full blood meal, 82% of the infected ones had engorged fully. Second, mosquitoes
      harbouring sporozoites were more likely to bite several people per night. Twenty
      two per cent of the infected mosquitoes, but only 10% of the uninfected
      mosquitoes, contained blood from at least two people. We conclude that the
      observed changes in blood-feeding behaviour allow the parasite to spread more
      rapidly among human hosts, and thus confirm that the parasite manipulates the
      mosquito to increase its own transmission.

PMID- 9628036
TI  - Phylogeography of Bufo marinus from its natural and introduced ranges.
AB  - The marine toad, Bufo marinus, has a broad natural distribution extending from
      the south-west of the USA to southern Peru and the central Amazon. It was
      introduced to several localities in the Caribbean and Pacific Oceans to control
      sugar cane pests. We sequenced 468 bp of mitochondrial DNA (mtDNA) containing the
      ND3 gene, and flanking tRNA genes from toads spanning the broad natural and
      introduced ranges. Consistent with the known history of introductions and
      expected effects of serial bottlenecks, mtDNA within introduced populations in
      Hawaii and Australia was uniform and most closely related to samples from eastern
      Venezuela and French Guiana. However, mtDNA nucleotide diversity in the
      geographic region spanning the source areas is also relative low (0.18-0.46%) and
      the absence of variation in the introduced populations precludes quantitative
      assessment of the reduction in genetic diversity. Unexpectedly, there was a large
      phylogeographic break (5.4% sequence divergence) within the natural range
      separating populations east and west of the Venezuelan Andes. We hypothesize that
      the two major lineages of B. marinus were isolated by the uplift of the eastern
      Andean cordillera which was completed approximately 2.7 Ma. Another species of
      the marinus group, B. paracnemis, had mtDNA paraphyletic, with marinus, being
      nested within the eastern lineage. Thus, at least one speciation event within the
      marinus group postdates the split within marinus. These findings suggest that the
      taxonomy of B. marinus should be re-evaluated and that the search for pathogens
      to control Australian populations should be conducted in populations from both
      lineages in the natural range.

PMID- 9628037
TI  - New phylogenetic perspectives on the Cervidae (Artiodactyla) are provided by the
      mitochondrial cytochrome b gene.
AB  - The entire mitochondrial cytochrome b (cyt b) gene was compared for 11 species of
      the artiodactyl family Cervidae, representing all living subfamilies, i.e., the
      antlered Cervinae (Cervus elaphus, C. nippon, Dama dama), Muntiacinae (Muntiacus
      reevesi), and Odocoileinae (Odocoileus hemionus, Mazama sp., Capreolus capreolus,
      C. pygargus, Rangifer tarandus, Alces alces); and the antlerless Hydropotinae
      (Hydropotes inermis). Phylogenetic analyses using Tragulidae, Antilocapridae,
      Giraffidae and Bovidae as outgroups provide evidence for three multifurcating
      principal clades within the monophyletic family Cervidae. First, Cervinae and
      Muntiacus are joined in a moderately-to-strongly supported clade of Eurasian
      species. Second, Old World Odocoileinae (Capreolus and Hydropotes) associate with
      the Holarctic Alces. Third, New World Odocoileinae (Mazama and Odocoileus)
      cluster with the Holarctic Rangifer. The combination of mitochondrial cyt b and
      nuclear k-casein sequences increases the robustness of these three clades. The
      Odocoileini + Rangiferini clade is unambiguously supported by a unique derived
      cranial feature, the expansion of the vomer which divides the choana. Contrasting
      with current taxonomy, Hydropotes is not the sister group of all the antlered
      deers, but it is nested within the Odocoileinae. Therefore, Hydropotes lost the
      antlers secondarily. Thus, the mitochondrial cyt b phylogeny splits Cervidae
      according to plesiometacarpal (Cervinae + Muntiacinae) versus telemetacarpal
      (Odocoileinae + Hydropotinae) conditions, and suggests paraphyly of antlered
      deer.

PMID- 9628038
TI  - Birth weight and neonatal survival of harbour seal pups are positively correlated
      with genetic variation measured by microsatellites.
AB  - We examined the relations between fitness-related traits of wild harbour seal
      (Phoca vitulina) pups with microsatellite heterozygosity, and with a measure of
      genomic diversity based on the mean squared distance between microsatellite
      alleles within an individual, mean d2. Birth weight was positively influenced by
      maternal age, pup sex, and either mean d2 or individual heterozygosity in
      separate multiple regression models. The association of birth weight with mean d2
      was stronger than that with heterozygosity, however. The factors maternal age,
      pup sex, and mean d2 combined to account for 36.8% of the variation in birth
      weight, with mean d2 accounting for the greatest explanatory power (52.3% of the
      variance explained). Pups which survived until weaning had significantly higher
      mean d2 than pups which died, independent of birth weight. These effects are
      consistent with heterosis resulting from recent population mixing, and/or
      inbreeding depression in this population. Mean d2 thus provides (i) a better
      measure of individual genetic variability than heterozygosity for microsatellite
      data; and (ii) a convenient tool for assessing the effects of inbreeding and
      outbreeding in natural populations.

PMID- 9628039
TI  - Paternal products and by-products in Drosophila development.
AB  - Tails of fertilizing spermatozoa persist throughout embryogenesis in Drosophila
      species and can be observed within the midguts of larvae after hatching.
      Throughout development, sperm proteins slowly diffuse or are stripped from the
      giant sperm tail residing within the embryo's anterior end. The shape and
      position of the sperm within the embryo are regulated such that, during organ
      formation, the unused portion of the sperm is enveloped by the developing midgut.
      This persistent, paternally derived structure is composed of the sperm's
      mitochondrial derivatives and appears to be defecated by the larva soon after
      hatching. These complex sperm-egg interactions may represent mechanisms to avoid
      intragenomic conflict by ensuring strictly maternal inheritance of mitochondrial
      DNA (mtDNA).

PMID- 9628040
TI  - Differential photohydrodehalogenation reactivity of bromobenzenes (1,2,4
      tribromobenzene, 1,2,3,5-tetrabromobenzene) and pentachlorobenzene: sunlight
      based remediation.
AB  - The photochemical dehalogenation of 1,2,4-tribromobenzene, 1,2,3,5
      tetrabromobenzene and pentachlorobenzene in open-air solutions of acetonitrile
      using natural and artificial sunlight as the irradiation source has been
      investigated. The regiochemistry of mono-dehalogenation has been determined for
      1,2,4-tribromobenzene and 1,2,3,5-tetrabromobenzene. Pentachlorobenzene did not
      react. 1,2,4-Tribromobenzene yielded three products, 1,4-dibromobenzene, 1,3
      dibromobenzene and 1,2-dibromobenzene with isomer percentages of 52 +/- 1%, 39 +/
      2% and 9 +/- 1%, respectively. 1,2,3,5-Tetrabromobenzene yielded 1,3,5
      tribromobenzene, 1,2,4-tribromobenzene and 1,2,3-tribromobenzene with relative
      product percentages of 60 +/- 2%, 29 +/- 2%, 11 +/- 1%.

PMID- 9628041
TI  - Synthesis of some novel 2-oxo-pyrano(2,3-b)- and 2-oxo-pyrido(2,3-b)quinoline
      derivatives as potential antimalarial, diuretic, clastogenic and antimicrobial
      agents.
AB  - The 2-chloro-3-formyl quinoline derivatives (1a-e) on treatment with acetic
      anhydride and sodium acetate, afforded the corresponding novel 2-oxopyrano(2,3-b)
      quinoline derivatives (2a-e), and these were subjected to ammonia treatment to
      yield the corresponding naphthyridine derivatives (3a-e). The prepared compounds
      (2a-e) were tested for their antimalarial, diuretic, clastogenic and
      antimicrobial properties. Not all the compounds showed a diuretic effect and the
      significant increase in the frequency of micronuclei shows that they are non
      clastogens, whereas the 7-chloro derivative (2e) was a very effective
      antimalarial agent against the mosquito species. All the compounds were found to
      have optimum antimicrobial activity against Staphylococcus aureus, Escherichia
      coli and Salmonella typhi. Compounds 2d and 2e were found to be most active
      against the bacteria tested.

PMID- 9628042
TI  - The perils of parity and privatization.

PMID- 9628044
TI  - Benefits and limitations of professional-family interactions: the family
      perspective.
AB  - Families of persons with severe mental illness often experience burden and stress
      related to the caregiving role. There is a paucity of research describing
      effective interventions for relieving this burden. This article reports the
      findings of a study that elicited families' perceptions of professional
      interventions. Two focus groups were conducted with relatives of persons with
      schizophrenia or bipolar disorder. Participants described their experiences of
      the illness, current concerns, and coping strategies. A major focus of the study
      was the families' evaluations of past and future interventions from health
      professionals. Content analysis of the data identified critical elements of
      supportive and nonsupportive behaviors from professionals. Recommendations for
      future interventions were identified.

PMID- 9628043
TI  - Invisible residents: the chronically mentally ill elderly in nursing homes.
AB  - This article presents results from a retrospective study of psychological
      assessments of elderly persons with chronic mental illness residing in nursing
      homes. All residents (N = 570) received this assessment as part of federally
      mandated screening for mentally ill persons residing in long-term care. The
      process, the Preadmission Screening and Resident Review, was mandated by the
      Omnibus Budget Reconciliation Act (OBRA 87). These assessments were the first
      stage in a process to determine if the nursing home was the most appropriate
      placement for each resident. If nursing home care was deemed appropriate, then a
      psychological treatment program was to be established within the nursing home
      setting. The sample ranged in age from 50 to 104 (mean of 70). The majority had a
      diagnosis of schizophrenia and a history of psychiatric hospitalization occurring
      early in their life. The assessments did not include any quantifiable data on
      activities of daily living, cognitive functioning, or level of psychiatric
      impairment. Therefore, the researchers coded the narrative data so that it could
      be interpreted. The majority functioned within the none-to-mild range of
      cognitive impairment, and very few were completely dependent in the need for
      physical care. The most recorded symptom was social withdrawal. Neuroleptic
      medications were administered to 64% of elderly persons with chronic mental
      illness. Importantly, there was no relationship between demographic or clinical
      information and treatment recommendations. Implications of these findings for
      psychiatric nurses are discussed.

PMID- 9628045
TI  - Development and testing the Elder Concerns about Memory Scale.
AB  - This article describes the development and testing of an instrument to measure
      elders' concerns about their memory. The content validity was assessed using a
      panel of experts. Internal consistency reliability and criterion-related and
      predictive validity were evaluated using three samples of community-based elders.
      This brief paper-and-pencil instrument should be helpful to nurse clinicians in
      numerous settings for assessing the magnitude of elder clients' concern and in
      planning appropriate interventions to address their distress.

PMID- 9628046
TI  - Genetics and alcoholism: implications for advanced practice psychiatric/mental
      health nursing.
AB  - This article uses the research findings on genetics and alcoholism as a basis for
      nursing practice. Alcoholism is a complex genetic disorder in which multiple
      genes and the environment interact and contribute to the disease process. Family,
      twin, and adoption studies have consistently shown the genetic influence on
      alcoholism. Animal and human studies are identifying biological and genetic
      markers for alcoholism. The results of these studies should direct nurses in
      assessing patients at risk, educating patients about the disease and the
      rationale for selected treatments, referring at-risk individuals to support
      groups, and using supportive therapy.

PMID- 9628047
TI  - Narrative therapy for women who have lived with violence.
AB  - Narrative therapy is proposed as a possible treatment approach for women who have
      had multiple experiences of sexual violence and abuse within the context of their
      intimate relationships. Narrative therapists elicit discussion of unique
      outcomes, which are moments of strength, autonomy, and emotional vitality hidden
      in life stories that are otherwise saturated with suffering and oppression, to
      open up possibilities for constructing new life narratives. Examples of such
      unique outcomes revealed to the author by individuals participating in a research
      project concerned with women's responses to sexual violence by male intimates are
      given.

PMID- 9628048
TI  - Inquiry-based learning and critical thinking in an advanced practice psychiatric
      nursing program.
AB  - The advanced practice psychiatric nurse must be prepared to meet the changing
      demands being placed on the nursing profession. Some changes are the product of
      health care reforms, especially managed care. Others are more fundamental,
      because continuing scientific advances drive rapid changes in the knowledge base
      required of mental health nurses. Curricular reforms initiated earlier this
      decade were intended to equip nurses with the problem-solving and critical
      thinking skills required to deal with novel and complex situations in a rapidly
      changing healthcare system. This article describes how the Inquiry-Based Learning
      tutorial method attends to the mental processes of graduate students and fosters
      critical-thinking skills.

PMID- 9628049
TI  - Psychiatry's Holy Grail: the search for the mechanisms of mental diseases.

PMID- 9628050
TI  - Teaching obstetrics at home: medical schools and home delivery services in the
      first half of the twentieth century.

PMID- 9628051
TI  - "Confusion's masterpiece": the development of the physician assistant profession.

PMID- 9628052
TI  - The development of the Office of Alternative Medicine in the National Institutes
      of Health, 1991-1996.

PMID- 9628053
TI  - Medical history from midcoast Maine.

PMID- 9628054
TI  - The diagnosis of infant psychopathology: current challenges and recent
      contributions.
AB  - In this paper we describe current difficulties in the diagnosis of infant
      psychopathology and two recent contributions to the assessment of infant
      psychopathology, "KIDDIES," and "Zero to Three." In order to accomplish this a
      literature review was completed regarding infant psychopathology and current
      diagnostic instruments. The literature supports the notion that there is a need
      for more empirical research in the area of infant psychopathologies and for more
      reliable and valid scales of infant psychopathology. Zero to Three and KIDDIES
      are useful tools in the assessment of psychopathology, and have complementary
      strengths.

PMID- 9628055
TI  - Parental perceptions of child vulnerability, overprotection, and parental
      psychological characteristics.
AB  - While a parental perception of child vulnerability to illness/injury is often
      used interchangeably with parental overprotection, research suggests that these
      constructs are independent. Distinct parental psychological characteristics were
      hypothesized for each construct. The parents of 871 children, ages 22-72 months,
      completed a four-part protocol (clinical background data, Child Vulnerability
      Scale, Parent Protection Scale, and Brief Symptom Inventory). A distinct parent
      symptom profile was found for perceived child vulnerability (somatization,
      obsessive-compulsiveness, and anxiety). Overprotection was associated with phobic
      anxiety, psychoticism, and paranoid ideation. These findings provide further
      support for the differentiation of these constructs.

PMID- 9628056
TI  - Self-reported delinquent behavior and psychosocial functioning in inner-city
      teenagers: a brief report.
AB  - Evaluated psychosocial characteristics of inner-city ninth graders exceeding a
      cutoff for clinically significant delinquent behaviors (n = 27), as compared to
      youth whose self-reported delinquent behaviors fell below this cutoff (n = 136).
      Youth reporting high levels of delinquent behavior reported more life stress,
      depression and anxiety, lower self-concept, and less cohesive families than other
      students. Females reporting high levels of delinquent behavior were more likely
      to have poor classroom and school attendance than other females; this
      relationship did not hold for males.

PMID- 9628057
TI  - Reliability of the Terry: a mental health cartoon-like screener for African
      American children.
AB  - Test-retest reliability and internal consistency of the Terry, a cartoon-based
      child mental health screener developed for African-American children, were
      measured in 36 boys (age 5 1/2 to 13) in a test-retest design. Reliability of the
      diagnosis (0.70 < or = k < or = 0.75) was good for ADHD, ODD, CD, and OAD, and
      excellent for MDD and SAD. Because of low base-rate, no kappa value was
      calculated for SPh. Both test-retest agreement, and reliability of the symptom
      scale (0.75 < or = ICC < or = 0.80) were very good for all 7 diagnoses. Internal
      consistency according to symptom scale (0.78 < or = Cronbach alpha < or = 0.90),
      was moderate for OAD, good for SPh, MDD, SAD, CD, and ODD, and excellent for
      ADHD. The Terry is a culturally-sensitive questionnaire with good reliability.

PMID- 9628058
TI  - Differences in caloric utilization in eating disordered adolescents.
AB  - Caloric utilization is an important aspect of the clinical management of eating
      disorders. Caloric intake and body weight of 32 inpatient bulimic and anorectic
      girls and 30 normal adolescents were measured. Normal weight bulimics ate fewer
      calories while anorectics ate more calories per kilogram body weight compared
      with the control group. Anorectics have greater difficulty to eat sufficient
      calories to maintain their weight. These findings indicate that treatment should
      be extended beyond the point of time where normal weight is reached.

PMID- 9628059
TI  - A comparison between the Weinberger Adjustment Inventory and the Minnesota
      Multiphasic Personality Inventory with incarcerated adolescent males.
AB  - Empirical work on psychopathology and delinquency requires concise and specific
      instruments. The Weinberger Adjustment Inventory (WAI), was correlated with the
      Minnesota Multiphasic Personality Inventory (MMPI) using a sample of incarcerated
      adolescent males (N = 178). The distress dimension of the WAI was significantly
      and positively associated with scales 2, 4 and 7 of the MMPI. The restraint
      dimension was significantly and positively associated with the Lie and K scales
      of the MMPI. Distress and restraint were distinct dimensions. The WAI may be a
      brief and helpful personality measure, determining responses to conflict and
      subjective stress in delinquents with poor reading skills and other special
      education impairments. The length of the WAI makes it especially suitable for
      populations such as incarcerated adolescent males who exhibit short attention
      spans and frequent episodes of noncompliant and resistant behavior.

PMID- 9628060
TI  - [Necessary extended surgery in gastric cancer. Our experience].

PMID- 9628061
TI  - [Carotid endarterectomy in patients with neurological non-side related (NSRS)
      symptoms].
AB  - Out of 970 carotid endarterectomies (CE) performed for high-grade (> 80%)
      stenosis of the internal carotid artery (ICA) until 1995, 147 patients with
      neurological non side-related symptoms (NSRS) and without any cardiac, ocular or
      vestibular significant pathology have been evaluated, analyzing the medium and
      long-term functional results (mean follow-up 37.6 months) related to the
      morphological status of the ICA contralateral and the vertebral arteries. NSRS
      disappeared in 126 pts (85.71%): contralateral ICA was non-stenotic in 32 cases
      (25.39%), stenotic < 75% in 68 cases (53.96%), stenotic > 75% in 7 cases (5.55%)
      and occluded in 19 cases (15.09%); vertebral arteries were pathological in only 6
      cases (4.75%), among which 4 were on the same side and 2 on the opposite side of
      CE. NSRS persisted in 20 pts (13.6%): contralateral ICA was non-stenotic in 5
      cases (25%), with a stenosis < 75% in 11 cases (55%) and with stenosis > 75% in 4
      cases (20%); vertebral obliterative lesions were 3 (15.78%), among which 1 on the
      same and 2 on the opposite side of CE. No one statistical comparison among the
      groups of cases obtained on the ground of the status of ICA and vertebral
      arteries were significant (p always > 0.05 at chi-square analysis). Authors' data
      confirmed that high grade stenoses of ICA can cause NSRS and that CE--always
      performed at the aim to prevent major neurological attacks--can relieve also
      these functional disorders in the most of cases, independently from the status of
      the contralateral ICA and the vertebral arteries.

PMID- 9628062
TI  - [Production of PSA by breast adenocarcinoma cells: preliminary results].
AB  - PSA has been measured out with highly sensitive method both in liquid of mammary
      cysts and in cytosol of neoplastic cells. Our data point out that dysplastic,
      metaplastic and anaplastic breast epithelial cells produce PSA. Such production
      is, probably, related to expression of hormonal receptors.

PMID- 9628063
TI  - [Intracystic papillary carcinoma of the breast. Personal experience].
AB  - The Authors, on the base of three cases of intracystic papillary carcinoma of the
      breast, discuss about the diagnostic means and the modalities of treatment of
      such rare cancer. They stress the value of cytology by fine needle aspiration,
      which gives more detailed informations than mammography or ultrasonography. As
      far as the treatment concerns, the Authors, according to the data of the
      literature, suggest for this tumor, still at an "in situ" stage, a conservative
      surgical treatment such as a quadrantectomy or tumorectomy plus lymphadenectomy
      followed both by radiotherapy. Finally, they remark that the intracystic
      papillary carcinoma of the breast, mainly arising in old women (7th, 8th decade),
      was found within their series (two out of three) in young women in the 5th decade
      of life.

PMID- 9628064
TI  - [Esophageal perforations. Diagnosis and treatment].
AB  - Perforation of the esophagus was retrospectively analysed in six patients. The
      age span was 30 years to 81 years, and the male to female ratio was 2 to 1. Each
      case was studied with regard to presentation, etiology, treatment and
      complications. The diagnosis was made at postmortem examination only in 1
      patient. The perforation was iatrogenic in 1 of the patients and spontaneous in
      5. Management was nonoperative in 3 cases and primary repair with drainage was
      performed in 2 patients. Overall mortality rate for the series was 33%. This
      series accumulated from a review of the literature emphasizes the importance of
      the influence of different methods of treatment and time lapsed between
      occurrence and therapy.

PMID- 9628065
TI  - [Acute hepatic necrosis in a patient treated with cyproterone acetate].
AB  - The Authors report a case of prostatic carcinoma in a 84 year old male, treated
      with cyproterone acetate (CPA), complicated by a fatal fulminant hepatitis. He
      was admitted with a mixed jaundice followed by a derange of all liver function
      tests. Serological markers for hepatitis were negative. Ultrasonography and CT
      revealed no hepatic abnormality but gallstones and dilatation of principal bile
      duct with a terminal stricture. By the endoscopic retrograde cholangiography and
      sphincterotomy we put an external drain tube. He died 9 days after admission.
      Fatal hepatis due to CPA is a very rare complication but all patients on anti
      androgenic drugs should have liver function closely monitored. CPA must be
      discontinued immediately at the first derange of liver function tests.

PMID- 9628066
TI  - [Adenocarcinoid of the appendix: a case report and anatomo-pathological and
      clinico-therapeutic considerations].
AB  - The Authors underline the most important pathological, clinical and therapeutic
      aspects of appendiceal adenocarcinoid. Appendiceal adenocarcinoid is quite a rare
      tumor, presently considered as a single entity; it differs from typical carcinoid
      of the appendix because of its well definite histology, its aggressive behaviour
      and its poorer prognosis. There are no precise prognostic and therapeutic
      criteria to direct the operative choice between appendectomy and hemicolectomy.
      In particular the tumor diameter is of no use since the tumor often present
      diffuse rather than nodular growth. According to most Authors appendectomy is not
      sufficient in the following cases: liver lymph-node or retroperitoneal
      metastases; cecal meso-appendiceal or peritoneal spreading; histological poorly
      differentiated tumors, with nuclear atypia and high mitotic count. Some Authors
      performed hemicolectomy and bilateral oophorectomy in all case with peritoneal
      involvement since the ovaries are a frequent site of metastases.

PMID- 9628067
TI  - [Preoperative treatment with interleukin-2 in colorectal carcinoma].
AB  - Thirteen surgical patients affected by colorectal cancer have been evaluated to
      study the effectiveness of a short-term preoperative therapy with interleukin-2
      (IL-2). Seven patients have been treated for three days before surgery with
      subcutaneous administration of IL-2 (9.000.000 U.I. b.i.d.). Six patients have
      been treated with placebo and have been considered as control group. All the
      patients have been operated upon 36-48 hours after the last administration of IL
      2 or placebo. The assays of CD-3+, CD-4+, CD-8+ e CD-56+ lymphocytes, evaluated
      preoperatively and 7 days after the operation, have showed a postoperative
      increase of CD8+ and CD56+ and a decreased ratio of CD4+/CD8+. The results of
      this study, although not conclusive, suggest a positive antitumoral response in
      patients treated preoperatively with IL-2. Further studies could be performed to
      evaluate the survival after such a treatment.

PMID- 9628068
TI  - [Digestive anastomosis in general surgery].
AB  - Still today the digestive anastomoses are a subject very discuss and
      controversial in relation to the better technique. In fact the introduction of
      mechanical suture has placed the problem between this instrumentation and the
      classic technique. The Authors, comparing these two techniques, observe the
      peculiar aspects of each one and relate on the progresses, in last years, whether
      of the mechanical suture, with the improvement of the handy and the resistance of
      the anastomosis, or the threads of suture, ever more inert and resistant.
      Subsequently, the Authors relate your experience showing the form of realization
      of the anastomoses in the esophagogastric surgery, small intestine, colon-rectum,
      hepato-biliary and pancreatic surgery. In particularly, about the hand-sewn
      anastomosis, the Authors relate personal technique of reconstruction with
      extramucosal continuous suture, one-layer, with synthetic slow absorbable one
      filament (PDS). In conclusion, the Authors declare that the introduction of the
      mechanical suture has certainly influenced the development of the new therapeutic
      solutions and has allowed intestinal anastomosis in sites of difficult access
      (abdominal esophagus, low rectum), but they think that the surgeon must to learn
      to know when is useless or neoplastic mechanical suture and he can realize
      manually the same anastomosis with quickness and safety.

PMID- 9628069
TI  - The role of CT in the diagnosis of small bowel obstruction: a case and literature
      review.
AB  - In cases of suspected small bowel obstruction, CT may confirm the diagnosis and
      demonstrate the cause of obstruction, preventing a delay in surgical treatment.
      This article reviews several recent cases which demonstrate the utility of CT in
      this clinical scenario. Also, a review of literature suggests that CT may have a
      role in differentiating simple from strangulated small bowel obstruction.

PMID- 9628070
TI  - Jack Hough, M.D.

PMID- 9628071
TI  - Change and quality.

PMID- 9628072
TI  - Diagnosis and treatment of attention deficit hyperactivity disorder in school age
      children. AMA Council on Scientific Affairs.

PMID- 9628073
TI  - Age of onset for ADHD.

PMID- 9628074
TI  - Nightmares treated with cyproheptadine.

PMID- 9628075
TI  - Risperidone and refusal to eat.

PMID- 9628076
TI  - Intranasal abuse of prescribed methylphenidate.

PMID- 9628077
TI  - Psychological testing for child and adolescent psychiatrists: a review of the
      past 10 years.
AB  - OBJECTIVE: To provide a review of psychological tests often used with children
      and adolescents. METHOD: A description of how psychological tests are used and
      how to interpret various types of scores is provided. Subsequently, psychological
      tests used to assess intelligence, academic achievement, neuropsychological
      functions, and personality are reviewed. RESULTS: There are numerous well-normed,
      reliable, and valid instruments that are available for assessing intellectual and
      academic functioning in children and adolescents. Neuropsychological tests,
      designed to assess objectively a wide range of cognitive functions, are available
      and extremely useful for designing treatment plans for patients with cognitive
      difficulties. Despite their popularity, most projective tests have relatively
      weak psychometric data supporting their reliability and/or validity. CONCLUSIONS:
      Psychological testing provides objective measures of behavior that are of
      considerable utility for evaluating children and adolescents. However,
      psychological test data, in isolation, will rarely be adequate for providing a
      DSM diagnosis, and test scores are best interpreted in the context of other
      clinical data. Psychological test data can be very useful for developing a
      comprehensive treatment plan that addresses the patient's cognitive and emotional
      needs.

PMID- 9628078
TI  - Cognitive-behavioral psychotherapy for children and adolescents with
      posttraumatic stress disorder after a single-incident stressor.
AB  - OBJECTIVE: To test the efficacy of a group-administered cognitive-behavioral
      psychotherapy (CBT) protocol for pediatric posttraumatic stress disorder (PTSD)
      after a single-incident stressor. METHOD: After a school-wide selection-to
      treatment procedure conducted in two elementary and two junior high schools,
      children and adolescents with DSM-IV PTSD by structured interview were entered
      into an 18-week, group-administered CBT protocol using a single case across time
      and setting experimental design. Assessments of PTSD, anxiety, depression, trait
      anger, locus of control, and disruptive behavior were conducted at baseline,
      posttreatment, and at 6-month follow-up. RESULTS: Experimental control across
      time (staggered start date) and setting (school and age) was demonstrated.
      Fourteen of 17 subjects completed treatment. Of these, 8 (57%) no longer met DSM
      IV criteria for PTSD immediately after treatment; 12 (86%) of 14 were free of
      PTSD at 6-month follow-up. On intent-to-treat analyses, treatment produced a
      robust beneficial effect posttreatment on the Clinician-Administered PTSD Scale
      Child and Adolescent Version, with additional improvement accruing at follow-up
      (p < .001). Improvements of a similar magnitude were seen for depression (p <
      .001), anxiety (p < .001), and anger (p < .005). Locus of control remained
      external from pre- to posttreatment but became strongly internal at follow-up (p
      < .001). CONCLUSION: More clinical trials are required to confirm that CBT is a
      safe, acceptable, and effective treatment for PTSD in children and adolescents.

PMID- 9628079
TI  - Adult physical health outcomes of adolescent girls with conduct disorder,
      depression, and anxiety.
AB  - OBJECTIVE: To examine the young adult physical health outcomes of adolescent
      girls with behavior problems. METHOD: Girls with conduct disorder, girls with
      depression, girls with anxiety, and healthy girls (N = 459) who had been
      evaluated at age 15 years were followed up at age 21, when general physical
      health, substance dependence, and reproductive health were assessed. RESULTS:
      After control for potentially confounding variables including prior health,
      adolescent conduct disorder predicted more medical problems, poorer self-reported
      overall health, lower body mass index, alcohol and/or marijuana dependence,
      tobacco dependence, daily smoking, more lifetime sexual partners, sexually
      transmitted disease, and early pregnancy. Adolescent depression predicted only
      adult tobacco dependence and more medical problems; adolescent anxiety predicted
      more medical problems. CONCLUSIONS: The robust link between female adolescent
      conduct disorder and poor physical health in adulthood suggests that intervention
      with girls who have conduct disorder may be a strategy for preventing subsequent
      health problems.

PMID- 9628080
TI  - General medical problems among the offspring of depressed parents: a 10-year
      follow-up.
AB  - OBJECTIVE: To examine the association between both parental and offspring
      depression and the general medical problems of a sample of offspring at high and
      low risk for depression. METHOD: Offspring (n = 222) from families with either
      depressed or nondepressed parents were followed up for a period of 10 years. Data
      collected included psychiatric diagnoses derived from direct semistructured
      interviews and history of general medical problems and hospital visits. Rates of
      medical problems and hospitalizations were calculated, and offspring were
      stratified by depression status of both parent and offspring. RESULTS: In
      analyses controlled for sociodemographic factors, offspring depression status was
      associated with a history of genitourinary disorders, headaches, respiratory
      disorders, other disorders, and hospitalizations in the offspring, and parental
      depression was associated with a history of unconsciousness and hospitalization
      in the offspring. After subjects were stratified by parental depression,
      significant associations between offspring depression and medical problems were
      found for only those offspring with a depressed parent. CONCLUSIONS: These
      findings suggest that a history of parental depression increases the risk for
      medical problems and hospitalization among depressed offspring. The co-occurrence
      of general medical and psychological problems among offspring of depressed
      parents may have implications for the treatment of both depression and comorbid
      medical disorders.

PMID- 9628081
TI  - Incidence and predictors of suicidal behaviors in a longitudinal sample of young
      adolescents.
AB  - OBJECTIVE: This analysis examines 1-year transition probabilities and baseline
      predictors for suicidal behaviors in young adolescents. METHOD: Adolescents from
      a two-stage, community-based longitudinal study were classified into suicidal
      behavior categories (attempt, plan, ideation, and none) for baseline and follow
      up years. Transition probabilities for movement among categories were calculated,
      and polytomous logistic regression analysis was used to examine predictors of
      suicidal behaviors. RESULTS: Among those with no suicidal behaviors at baseline,
      1-year incidence rates were 1.3% for attempts and 1.7% each for plans and
      ideation. Increasing family cohesion was protective for suicide attempts (odds
      ratio [OR] = 0.9). Female subjects were more likely than males to report plans
      (OR = 8.9) and ideation (OR = 4.1). Increasing impulsivity (OR = 2.3), prior
      suicidal behavior (OR = 10.6), and undesirable life events (OR = 1.1) were
      significant predictors of plans. CONCLUSIONS: While there are a number of
      predictors of suicidal behaviors, the false-positive rate is high. Focusing on
      proximal risk factors, particularly stressors in adolescent development, may
      overlook the fundamental role of underlying mental disorder and familial factors-
      both biological and environmental. Suicide and suicidal behaviors are the result
      of a constellation of adverse factors requiring a range of interventions for
      prevention.

PMID- 9628082
TI  - Social role functioning by adolescents with psychiatric disorders.
AB  - OBJECTIVE: To identify aspects of social role functioning that are impaired in
      adolescents with specific psychiatric disorders in order to improve the
      psychiatric taxonomy and clinical knowledge base. METHOD: Adolescents in four
      urban public schools were screened for mental health problems. Structured
      psychiatric interviews (National Institute of Mental Health Diagnostic Interview
      Schedule for Children Version 2.2) with 288 adolescents and their mothers were
      used to identify youths with psychiatric disorders, and 10 aspects of social role
      functioning were assessed. Aspects of social role functioning that discriminated
      between youths with and without psychiatric disorders and between those with
      emotional disorders and those with disruptive disorders were identified for boys
      and for girls. RESULTS: Boys with any type of disorder and all youths with
      disruptive disorders had significant, consistent impairment in academic
      performance and several other areas of functioning. Youths with emotional
      disorders, especially girls, demonstrated impairment in social activity
      participation and peer acceptance, but girls with disorders were not as
      consistently different from those without as were the boys with emotional
      disorders. CONCLUSIONS: Role functioning differs in important ways between youths
      with and without psychiatric disorders and between girls and boys with disorders.
      The results underscore the importance of investigating observable aspects of role
      behavior in order to improve the timely detection and effective management of
      psychiatric disorders in youth.

PMID- 9628083
TI  - Parent-child agreement on refugee children's psychiatric symptoms: a
      transcultural perspective.
AB  - OBJECTIVE: To compare the types and rates of psychiatric symptoms of young
      Central American and Cambodian refugees, as reported by both parents and
      children, and to examine parent-child agreement in reporting symptoms. METHOD:
      Interviews were conducted with 123 children aged 8 to 12 years and 158
      adolescents aged 12 to 16 years and their parents. Parents assessed psychiatric
      symptoms via the Child Behavior Checklist, the 8- to 12-year-olds responded to
      the Dominic, and the adolescents answered the Youth Self-Report. Means of
      Internalizing and Externalizing scores were compared on the basis of ethnic
      origin, parent's sex, and child's sex, as were the Spearman correlation
      coefficients of parents' and children's ratings. RESULTS: The Cambodian parents
      reported few symptoms in their children, and the Central Americans reported
      almost as many symptoms as did parents in U.S. clinical samples. The Cambodian
      children reported less symptoms than the Central Americans, but the interethnic
      difference was not significant in the adolescents' self-reports. Parent-child
      agreement varied considerably by sex and ethnic origin of the informant.
      CONCLUSIONS: The results underscore the need to involve multiple informants in
      assessing psychiatric symptoms of refugee children in spite of the difficulties
      inherent in field research with this population. They also show that data on
      multiple informants gathered from Western samples are not universally valid.

PMID- 9628084
TI  - Sleep disturbances in children with attention-deficit/hyperactivity disorder.
AB  - OBJECTIVE: To evaluate the relationship between sleep disturbances and attention
      deficit/hyperactivity disorder (ADHD). METHOD: Empirical research published since
      1970 on sleep disturbances in children with ADHD was systematically reviewed. A
      "box-score" approach was used to examine consistency of findings across the
      studies, which used different outcome measures. RESULTS: Although subjective
      accounts of sleep disturbances in ADHD were prevalent, objective verification of
      these disturbances was less robust. The only consistent objective findings were
      that children with ADHD displayed more movements during sleep but did not differ
      from normal controls in total sleep time. An additional finding was that
      stimulant medication led to changes in the children's sleep (e.g., prolonged
      sleep latency, increased length of onset to first rapid eye movement cycle), but
      these changes were believed to be nonpathological. CONCLUSIONS: The exact nature
      of the sleep problems in children with ADHD remains to be determined. Many of the
      relevant issues have not been adequately addressed. Factors such as poorly
      defined diagnostic groups, small sample sizes, few studies, and methodological
      and procedural limitations make it difficult to determine the relationship
      between ADHD and sleep problems.

PMID- 9628085
TI  - Premorbid prevalence of ADHD and development of secondary ADHD after closed head
      injury.
AB  - OBJECTIVE: To determine premorbid prevalence of attention-deficit hyperactivity
      disorder (ADHD) in children with moderate and severe closed head injury (CHI), to
      determine incidence of ADHD 1 year after injury, and to characterize children who
      develop ADHD by demographic, neuropsychiatric, and outcome variables. METHOD:
      Ninety-nine children who had severe and moderate CHI were followed up for 1 year.
      Premorbid and 1-year postinjury psychiatric status were ascertained by parent and
      child structured interviews and questionnaires measuring affective lability,
      aggression, apathy, and social judgment. RESULTS: Premorbid prevalence of ADHD
      was 0.20, significantly higher than in a reference population (0.045). Fifteen of
      the remaining 80 children (0.19) developed full ADHD criteria (except for age of
      onset) by the end of the first year. Children who developed secondary ADHD (S
      ADHD) had significantly greater premorbid psychosocial adversity, posttraumatic
      affective lability and aggression, posttraumatic psychiatric comorbidity, and
      overall disability than children who did not develop S-ADHD. CONCLUSIONS: There
      is an excess prevalence of premorbid ADHD among children who present with
      moderate and severe CHI. Children with high psychosocial adversity are more
      likely to develop S-ADHD after CHI. S-ADHD has criteria in common with
      personality change due to CHI, a deficit in behavioral inhibition being the major
      overlapping feature.

PMID- 9628086
TI  - Clonidine challenge in childhood anxiety disorder.
AB  - OBJECTIVE: To evaluate the neurohormonal and subjective mood response of children
      with anxiety disorder to clonidine challenge METHOD: Children with DSM-IV
      diagnoses of anxiety disorder (ANX) (n = 24) and normal controls (n = 15) were
      given a challenge of intravenous clonidine (1.3 micrograms/kg) and provided
      neurohormonal and mood self-report assessment over a 180-minute period. RESULTS:
      The ANX group differed from normal controls in Hamilton Anxiety Rating, Revised
      Children's Manifest Anxiety Scale score, and maximum change from baseline (delta
      max) in growth hormone (GH). Clonidine-stimulated GH concentration of the ANX
      group was significantly elevated compared with that of controls but returned to
      baseline within 2 hours. A subgroup with obsessive-compulsive disorder (OCD) (n =
      9) had significantly higher delta max GH (17.5 +/- 10.1 ng/mL) than the group
      with other anxiety disorders (ANX-OCD) (9.1 +/- 5.8 ng/mL) and controls (5.7 +/-
      4.1 ng/mL). CONCLUSION: GH response to clonidine challenge is not blunted in ANX
      subjects. This finding is in contrast to adult disorder and suggests that
      adrenergic postsynaptic receptor down-regulation is not a feature of childhood
      anxiety. These findings suggest enhanced central adrenergic sensitivity in ANX
      which is most pronounced in OCD and argue against a neurobiological continuum
      from childhood to adult anxiety disorder.

PMID- 9628087
TI  - Case study: caudate glutamatergic changes with paroxetine therapy for pediatric
      obsessive-compulsive disorder.
AB  - Neurobiological models for obsessive-compulsive disorder (OCD) have consistently
      implicated the caudate nucleus in the pathophysiology of this disorder. OCD
      symptoms improved markedly in a 9-year-old boy treated with paroxetine, a
      selective serotonin reuptake inhibitor, for whom pre/posttreatment proton
      magnetic resonance spectroscopic examinations were acquired to assess the
      relationship between neurochemical profile in the caudate nucleus, symptom
      severity, and treatment with paroxetine. Striking changes of the glutamate
      resonance in the caudate were observed after 12 weeks of paroxetine treatment.
      These data provide further support for glutamatergic-serotonin pathway
      involvement in the caudate nucleus of OCD patients.

PMID- 9628088
TI  - Case study: cyproheptadine and aggression in a five-year-old boy.
AB  - Cyproheptadine is an antihistamine and serotonin antagonist given to children for
      allergies, migraine headaches, and growth problems. A 5-year-old boy began to
      have episodes of violent behavior after the initiation of cyproheptadine therapy.
      After cyproheptadine was discontinued, the aggression ceased over the course of a
      few weeks. Although there are other causal explanations possible in this case,
      cyproheptadine seems the most likely cause of the violent behavior, especially in
      view of the literature on the relation between serotonin and aggression.

PMID- 9628089
TI  - A primer on homophobia for the child and adolescent psychiatrist.

PMID- 9628090
TI  - Development of the cerebral cortex: VI. growth factors: I.

PMID- 9628091
TI  - Is there a microbiological rationale for single-dose treatment of leprosy?

PMID- 9628093
TI  - Impaired responses to Mycobacterium leprae antigens in rhesus monkeys
      experimentally inoculated with simian immunodeficiency virus and M. leprae.
AB  - Seven of eight rhesus monkeys (RM) coinfected with simian immunodeficiency virus
      (SIV) and Mycobacterium leprae harboured acid-fast bacilli (AFB) at sites of
      dermal inoculation and/or at disseminated sites at times of humane sacrifice (up
      to 270 days post-M. leprae inoculation) due to SIV-induced debilitation or, in
      one long term survivor's case, to date over 3 years post-M. leprae inoculation.
      Detectable AFB were cleared in biopsies of inoculation sites of RM inoculated
      with M. leprae alone after 63 days postinoculation; these sites have, so far,
      remained AFB-negative, thereafter. Compared to animals infected with M. leprae
      alone, RM coinfected with SIV plus M. leprae showed: 1, completely suppressed
      serum antibody responses to M. leprae-specific PGL-I antigen, but strong anti-SIV
      Gp120 antibody responses; 2, impaired sensitization of blood mononuclear cells
      (MNC) to in vitro recognition of M. leprae-specific antigens in blastogenic
      stimulation assays; 3, impaired in vitro responses of blood MNC to nonspecific
      (ConA) blastogenic stimuli; and 4, early post-M. leprae inoculation, there was a
      significant incremental diminution of percentages of blood CD4+CD29+ T-cells in
      addition to the existing SIV-induced diminished percentages of CD4+CD29+ T-cells.
      The results indicate that humoral and cellular immune responses to M. leprae
      antigens are compromised in M. leprae-inoculated RM previously infected with SIV.
      These results provide an immunologic basis for the demonstration of enhanced M.
      leprae persistence or leprosy susceptibility in SIV-M. leprae coinfected RM.

PMID- 9628092
TI  - Protective immunization of monkeys with BCG or BCG plus heat-killed Mycobacterium
      leprae: clinical results.
AB  - Rhesus and sooty mangabey monkeys (RM and SMM) were vaccinated and boosted with
      BCG or BCG + low dose (LD) or high dose (HD) heat-killed Mycobacterium leprae
      (HKML). One group was not vaccinated. Except for a group of controls, all monkeys
      were challenged with live M. leprae. All animals were studied longitudinally to
      determine antileprosy protective efficacy. BCG reduced the numbers of RM with
      histopathologically-diagnosed leprosy by 70% and slowed and ameliorated the
      appearance of symptoms. BCG + LDHKML reduced the number of RM with leprosy by 89%
      and BCG + HDHKML by 78%. BCG did not protect SMM from developing leprosy, but
      disease progress was slowed; disease in SMM was exacerbated by the addition of
      HKML to the vaccine. RM, as a species, are prone to paucibacillary (PB) forms of
      leprosy, whereas SMM are prone to multibacillary (MB) forms. Thus, BCG
      vaccination offers significant protection from clinical disease and
      slows/ameliorates the rate of progression/degree of disease at the PB end and
      appears to at least ameliorate symptoms at the MB end of the leprosy spectrum.
      BCG + HKML protects at the PB end and exacerbates disease progress at the MB end
      of the leprosy spectrum.

PMID- 9628094
TI  - Leprosy and renal transplantation.
AB  - Nine cases of leprosy in patients treated at a large renal transplant centre in
      South Asia are described. Three had leprosy diagnosed before transplantation and
      had either completed or were continuing chemotherapy at the time of
      transplantation. One showed exacerbation of undisclosed leprosy after
      transplantation. Five patients developed the disease for the first time 22 months
      to 12 years after transplantation. Immunosuppression did not adversely affect the
      treatment of leprosy in any of the patients though concurrent liver disease
      required cessation of rifampicin in one patient.

PMID- 9628095
TI  - The National Leprosy Control Programme of Zimbabwe a data analysis, 1983-1992.
AB  - Prevalence and detection rates of leprosy in Zimbabwe as well as patient
      characteristics were reported by the National Leprosy Control Programme over the
      10-year period 1983-1992. The control programme made a new start in 1983 when
      multidrug therapy was introduced. Prevalence per 10,000 population declined
      steeply from 3.78 in 1983 to 0.52 in 1987. Prevalence continued to decline to
      0.22 in 1992 and was highest in the north-eastern provinces. After an initial
      increase, the detection rate per 10,000 had declined from 0.19 in 1985 to 0.08 in
      1992. The proportion of refugees among new cases had gradually increased since
      1988 and amounted to one third in 1991 and 1992. An analysis of records of 802
      cases who were newly detected from 1983 to 1992 showed that 51% were of the
      multibacillary (MB) type, 33% had visible disabilities at detection, 5% were
      under 15 years of age while the average delay time was 2.6 years. Patients with
      disabilities reported a longer delay time, were more often men and had more often
      the MB type of leprosy. The data suggest that transmission of leprosy is low but
      that cases are not diagnosed early enough to prevent transmission altogether.

PMID- 9628096
TI  - Evaluation of a sustained 7-year health education campaign on leprosy in Rufiji
      District, Tanzania.
AB  - To assess the impact of a 7-year intensive health education campaign about
      leprosy delivered by workers of the Kindwitwi Leprosy Trust to schoolchildren and
      general public in Rufiji District. Knowledge, attitude and beliefs towards
      leprosy were measured in Rufiji and compared to neighbouring Kisarawe District as
      control. Lessons learned from this analysis may be useful for the planning and
      evaluating of health education campaigns. Interview of schoolchildren, general
      public, community leaders, traditional healers and medical staff in both
      districts. A stratified randomized sampling scheme was used, with stratification
      for urban and rural settings. A representative sample of schoolchildren, general
      public, community leaders, traditional healers and medical staff in Rufiji
      District and in the control area of Kisarawe District was interviewed. The
      interviews were partly structured and partly open. The results of the interviews
      were analysed in the context of epidemiological leprosy data from 1985 till 1995,
      and demographic data of both districts. Data entry and statistical analysis was
      done using FileMaker Pro, Stata and Excel computer packages. We did not observe
      positive effects of the health education campaign on the indicators regarding
      early diagnosis of leprosy with less disability. Leprosy case detection was
      declining in both districts. We found that the campaign had a favourable impact
      on the knowledge and the attitude of schoolchildren in Rufiji District. We could
      demonstrate a relationship between increased knowledge of leprosy and a positive,
      less stigmatizing attitude. Knowledge of leprosy was better in Rufiji as compared
      to Kisarawe, but only among schoolchildren. We found indications that low level
      of education, rural residence, older age, female gender and Moslem religion were
      associated with stigmatizing attitudes and beliefs towards leprosy. Knowledge
      about leprosy reactions among medical staff interviewed was not optimal. The
      exact outcome of the sustained campaign in Rufiji District was difficult to
      assess because no comparison could be made with the situation prior to the
      campaign. However, the health education campaign was associated with increased
      knowledge and diminished tendency to stigmatize leprosy among schoolchildren.
      Health education campaigns have to be sustained and have to cover a broad sector
      of the society in order to induce behavioural changes in the community. The focus
      of health education should be rural communities and schools, and pay special
      attention to women, religious leaders and traditional healers. Awareness of
      diagnosis and treatment of leprosy reactions among medical staff should be
      improved.

PMID- 9628097
TI  - Editorials, September 1997 by W. C. S. Smith and P. Fine & D. K. Warndorff.

PMID- 9628098
TI  - Single-dose rifampicin, oflaxicin and minocycline (ROM) therapy for single
      leprosy lesions.

PMID- 9628099
TI  - Uveitis in leprosy patients who got inactive condition in pre-WHO/MDT era.

PMID- 9628100
TI  - Comment: ulnar abscess--4 months after release from control with paucibacillary
      multidrug therapy.

PMID- 9628101
TI  - Criminal negligence in medical practice.

PMID- 9628102
TI  - Some curious stories about Guy's Hospital.

PMID- 9628103
TI  - The management and implications of drug abusers in custody.

PMID- 9628104
TI  - Why do the media get healthcare stories so wrong?

PMID- 9628105
TI  - Designating parents in surrogating pregnancies.

PMID- 9628106
TI  - Lecture on anaesthesia.

PMID- 9628107
TI  - Legal aid.

PMID- 9628108
TI  - Idiopathic hypersomnia.
AB  - Identification of idiopathic hypersomnia dates back 20 years only. It typically
      consists of prolonged nocturnal sleep, great difficulty waking up in the morning
      or at the end of a nap, and constant or recurrent excessive daytime sleepiness.
      Complete and incomplete forms are encountered. Twenty-three subjects fulfilling
      ICSD criteria are reported with clinical, polysomnographic and immunogenetic
      data. Considering differential diagnosis is an important step in the diagnosis of
      idiopathic hypersomnia. Idiopathic hypersomnia is much less frequent than
      narcolepsy. A strong genetic component is suggested by the high proportion of
      familial cases. No association with HLA has been evidenced to date.

PMID- 9628109
TI  - Effect of frequent brief awakenings from nonREM sleep on the nonREM-REM sleep
      cycle.
AB  - In the framework of a selective sleep deprivation study, eight young men were
      repeatedly awakened during 3 nights from nonREM sleep (nonREMS). The mean number
      of awakenings per night was 27.4, 29.5 and 32.8. In order to avoid excessive
      suppression of slow wave sleep, no awakening occurred in the first nonREMS
      episode. Compared to baseline, cycle 2 was significantly prolonged in all 3
      nights, and cycle 3 in night 3 only. However, after subtracting the waking
      intervals, the differences from baseline was eliminated. The results show that
      the mechanisms underlying sleep cycle control keep track of sleep time and
      disregard epochs of waking.

PMID- 9628110
TI  - Effects of daytime activity upon the timing of REM sleep periods during a night.
AB  - The effects of mental and physical daytime activities upon REM sleep cycle (REM
      cycle) during 1 night was studied in five university students (aged 19-25 years).
      Mental activity with high tension has effects upon the timing of REM sleep
      periods in the later part of the night. Physical activity has effects upon the
      timing of REM sleep in the early part of the night. The result suggests that
      mental and/or physical activities during daytime modulate REM cycle during the
      night.

PMID- 9628111
TI  - Bifurcation properties of the two process model.
AB  - Daan's two process model is known to be one of the most powerful models, covering
      various situations from free-running to sleep deprivation. In this study,
      bifurcation properties of the model dynamics as function of a gap, D, between the
      threshold processes are clarified using a circle map. As a function of D, we will
      show that the model has the different types of the mutual entrainment regions
      that are intervened by the tangent bifurcation. The variable behavior of human
      circadian rhythm is suggested to be systematically understood based on the
      bifurcation properties of the two process model.

PMID- 9628112
TI  - Influence of cedar essence on spontaneous activity and sleep of rats and human
      daytime nap.
AB  - We investigated whether exposure to the odor of extracted cedar essence (CE) has
      (i) an influence on spontaneous activity and sleep-wake states of rats and (ii) a
      sleep-promoting effect on human daytime nap after taking an ordinary night's
      sleep. In rats exposed to CE, spontaneous activities and amount of wake were
      significantly decreased, while the amount of non-rapid eye movement (NREM) sleep
      was significantly increased. In human daytime nap, NREM sleep stage 2 latency was
      significantly shortened after exposure to CE.

PMID- 9628113
TI  - Effects of Hemerocallis on sleep in mice.
AB  - Freeze-dried flowers of the Akinowasuregusa (Hemerocallis fulva L. var.
      sempervirona M. Hotta), a Hemerocallis genus of the lily family, were fed to
      C57BL strain mice. The slow wave sleep and paradoxical sleep of the Hemerocallis
      treated group increased during the dark period. The differences between the
      control group and the Hemerocallis-treated group were significant (P < 0.05). The
      Hemerocallis feeding did not cause a change in sleep time during the light
      period. As a result, there was no significant change in the sleep-time percentage
      over a 24-h period.

PMID- 9628114
TI  - Effect of night exercise on the following partially deprived sleep.
AB  - Six trained male athletes (aged 24.3+/-2.9 years) performed cycling exercise from
      23.00 to 23.50 h. From 00.30 to 07.00 h, the subjects followed a schedule that
      consisted of 30 min trying to fall asleep in bed and 60 min of being awake
      outside the bedroom. The control experiment was conducted without exercise under
      the same time schedule. An increase in rectal temperature induced by exercise was
      1.9+/-0.4. After exercise, prolongation of sleep onset latency was observed only
      in the sleep period fron 00.30 to 01.00 h compared with the control night. Time
      spent in slow wave sleep throughout the night was significantly longer after
      exercise.

PMID- 9628115
TI  - Effects of the timing of exercise on the night sleep.
AB  - The effects of physical exercises taken at different times in the day upon
      subjective sleep feeling were examined in five healthy university students (aged
      20-22 years); morning exercise, evening exercise, and late evening exercise. The
      late evening exercise with the strength of 50-60% VO2max of 1 h has the effect of
      getting better subjective sleep feeling in the morning and the effect of the
      decreased daytime sleepiness.

PMID- 9628116
TI  - Changes in sleep patterns during He-O2 saturation dives.
AB  - During simulated hyperbaric saturation diving experiments of He-O2 mixture at the
      depths of 150, 180 and 230 m the standard polysomnography of four divers, as well
      as their subjective feelings of fatigue, were recorded for 268 nights. In all
      three diving conditions, during the bottom period and the decompression period,
      wakes after sleep onset and Stage 1 sleep increased while Stage 4 sleep
      decreased. In deeper diving conditions stage 4 sleep tended to decrease and
      subjective feelings of fatigue increased. When the results are considered it can
      be assumed that the deeper the diving depths, the increased sleep disturbances
      and fatigue. However, it is believed that a fundamental sleep pattern will be
      maintained.

PMID- 9628117
TI  - How does the distention of urinary bladder cause arousal?
AB  - Under urethane anesthesia, the urinary bladder of male rats was distended by 0.3
      0.5 mL of saline. When the animals displayed large amplitude delta waves, the
      distention caused tonic excitation in 76% (19/25) of the noradrenergic neurons in
      the locus coeruleus and in 53% (16/30) of the cholinergic neurons in the
      laterodorsaltegmental nucleus. The response was followed by a shift of
      electroencephalogram (EEG) pattern to faster waves of smaller amplitude. When EEG
      amplitude was faster and smaller, the same stimuli caused no response. Neurons in
      Barrington's nucleus were excited by a small amount of bladder distention
      independent of EEG patterns. These results suggest that the transition of state,
      caused by bladder distention, from deep sleep to light sleep is mediated by
      noradrenergic and cholinergic neurons in the brainstem.

PMID- 9628118
TI  - Comparison of event related potentials with and without hypnagogic imagery.
AB  - It is hypothesized that when hypnagogic imagery occurs, an appropriate attention
      may allocate to the imagery, resulting in the allocation of attention to the
      external tone stimuli being diminished. N3 amplitude of event related potentials
      (ERP) obtained a significant difference between the conditions with and without
      imagery. Arousal level of behavior and electroencephalography were not different
      between the conditions, therefore it is interpreted that the decrease of the N3
      amplitude during imagining reflects the diminution of the allocation of attention
      to the external tone stimuli. Another late component of ERP, P3, did not make
      clear peaks in this study despite a large time constant (tau=3.2 s) used for EEG
      records.

PMID- 9628119
TI  - Topographic mapping of electroencephalography coherence in hypnagogic state.
AB  - The present study examined the topographic characteristics of hypnagogic
      electroencephalography (EEG), using topographic mapping of EEG power and
      coherence corresponding to nine EEG stages (Hori's hypnagogic EEG stages). EEG
      stages 1 and 2, the EEG stages 3-8, and the EEG stage 9 each correspond with
      standard sleep stage W, 1 and 2, respectively. The dominant topographic
      components of delta and theta activities increased clearly from the vertex sharp
      wave stage (the EEG stages 6 and 7) in the anterior-central areas. The dominant
      topographic component of alpha 3 activities increased clearly from the EEG stage
      9 in the anterior-central areas. The dominant topographic component of sigma
      activities increased clearly from the EEG stage 8 in the central-parietal area.
      These results suggested basic sleep process might start before the onset of sleep
      stage 2 or of the manually scored spindles.

PMID- 9628121
TI  - Some sensory stimuli generate spontaneous K-complexes.
AB  - The present study was performed in order to determine whether spontaneous K
      complex are induced by sensory stimuli. Electroencephalogram (EEG) segments in
      stage 2 sleep containing an evoked K-complex or spontaneous K-complex were
      separately averaged with respect to the peak of N300, one of the main components
      constituting the K-complex. Small negative and positive components were found
      immediately before the main components of spontaneous K-complex in averaged EEG.
      These two components were judged to correspond to N100 and P200 induced by the
      sound stimulus. The present findings suggest that the spontaneous K-complex is
      not a spontaneous phenomenon but that it is induced by sensory stimuli.

PMID- 9628120
TI  - A negative component on event related potential recorded in the drowsy state.
AB  - Behavior of event related potential (ERP) components in the drowsy state was
      examined in nine subjects using oddball paradigm. A component with peak latency
      of 300 msec, N300, was superimposed on ERP in the drowsy state. N300 appeared
      also in stage 1 of NREM sleep and closely resembled vertex sharp wave evoked by
      sound stimulation in both scalp distribution and peak latency. It was suggested
      that N300 recorded in the drowsy state and vertex sharp wave recorded in stage 1
      of NREM sleep are generated by the identical synchronizing mechanism in the
      brain.

PMID- 9628122
TI  - Cortical activity of REM sleep often occurs earlier than other physiological
      phenomena.
AB  - N300 appearing in response to sound stimulus was used as an index to determine
      the occurrence of cortical activity characterizing REM sleep. In 5/10 subjects,
      marked reduction of N300 amplitude occurred even in the period of 0.5-2.5 min
      immediately preceding the appearance of muscle atonia characterizing REM sleep.
      Neither muscle atonia nor rapid eye movements appeared prior to the marked
      reduction of N300 amplitude in any subject. This suggests that the cortical
      activity characterizing REM sleep sometimes occurs a few minutes (or less)
      earlier than other physiological phenomena.

PMID- 9628123
TI  - Alcohol effect on sleep electroencephalography by fast Fourier transformation.
AB  - The influence of alcohol (ethanol) on sleep was investigated in 10 men.
      Polysomnography (PS) was recorded on a baseline night (BL-N) and an ethanol (0.8
      g/kg) night (Et-N). On visual score rapid eye movement (REM) sleep was reduced,
      REM latency was prolonged on Et-N as compared to BL-N. Using the fast Fourier
      transformation method, electroencephalographic power density of REM sleep in
      delta frequencies band and in the 10-12 Hz range of non-REM sleep were enhanced.
      REM sleep and non-REM sleep changes were prominent in the second-half and first
      half of the night, respectively.

PMID- 9628124
TI  - Efficacy of L-846 in patients with insomnia: evaluation by polysomnography.
AB  - The effects of L-846, an ultra-short-acting pyrazolopyrimidine hypnotic, on sleep
      were studied in nine insomniacs and two neurotic patients with insomnia. The
      patients were randomly assigned to receive 5 mg (n=6) or 10 mg (n=5) L-846. The
      study schedule comprised of one adaptation night, two baseline nights, three drug
      nights, and two withdrawal nights. Sleep latency and slow wave sleep (SWS)
      latency was largely shortened and %SWS increased in the early phase of sleep. No
      clear evidence of rebound insomnia was noted.

PMID- 9628125
TI  - Evaluation of human activities and sleep-wake identification using wrist
      actigraphy.
AB  - The purpose of this study is to investigate the count-characteristics of wrist
      actigraphy in basic human activities and to discuss the agreement of sleep-wake
      identification between polysomnography (PSG) and wrist actigraphy during
      nocturnal sleep. There was a distinct distribution of actigraphy counts over the
      studied activities. The evaluation of sleep-wake scoring using the wrist
      actigraphy agreed 96.9% with the polysomnographic scoring during nocturnal sleep.

PMID- 9628126
TI  - Evaluation of the Actillume wrist actigraphy monitor in the detection of sleeping
      and waking.
AB  - This study evaluated the Actillume instrument and the modified Action 3 sleep
      wake scoring algorithm, in which the scoring factor (P) was set at 0.10, 0.14,
      0.20, 0.30, 0.40 and 0.50. Fifteen subjects, each of whom underwent
      polysomnography with simultaneous wrist actigraphy four times, yielded a total of
      60 sleep studies. The sleep data from each subject were divided into four groups.
      In the high sleep efficiency index groups of the calibration and validation
      samples, the accuracy of the algorithm significantly differed within six P-values
      and was highest at P=0.14. In the low sleep efficiency index groups of both
      samples, however, there were no significant differences in the accuracy. Thus,
      these results indicate that P=0.14 should be most appropriate for this actigraph
      and algorithm.

PMID- 9628127
TI  - Validity of sleep log compared with actigraphic sleep-wake state.
AB  - Seven women and 11 men, mean age 30.1 years, kept a sleep log for 5-7 days, and
      their wrist activity was monitored each minute. Sleep-wake state in the sleep log
      and actigraphic sleep-wake state were compared, and the sensitivity and
      specificity of the sleep log were calculated for each subject. The ratio of
      agreement between these two parameters was computed for each subject. The
      sensitivity and specificity of the sleep log were 72.73-97.56% (mean 86.71%) and
      92.85-99.68% (mean 97.04%), respectively. The agreement ratio was 87.30-97.85%
      (93.48%), but 1-h agreement ratios from midnight dropped during the sleep onset
      period.

PMID- 9628128
TI  - The effects of time constant on electrooculographic recording of slow eye
      movements during the wake-sleep transition.
AB  - This study examines distortions in electrooculogram (EOG) wave form of slow eye
      movements (SEM) during the wake-sleep transition. Distortions in AC-coupled EOG,
      which were evaluated by computing Pearson's product-moment correlation
      coefficient between DC- and AC-coupled EOG, decreased as a function of time
      constants (0.3, 3 and 6 s) and showed SEM-dependent changes. Time constants of
      longer than 3.0 s should be chosen to reliably recognize SEM.

PMID- 9628129
TI  - Observational assessment of patient's sleep complaints in the coronary care unit.
AB  - Sleep-wake disorders are common in patients who are treated in coronary care
      units (CCU). We report a clinical trial aimed at developing an observational
      assessment of patients sleep complaints in a CCU. Thirty-four inpatients with
      coronary heart diseases in the CCU (Tokyo Metropolitan Hiroo General Hospital)
      participated in the study. The patient's sleep state was assessed by nursing
      staff and classified as wakefulness, drowsy and asleep according to a semi
      structured observation. Subjective sleep feelings upon rising was also
      investigated. Sleep disruptions during the latter half of the night was found to
      be an important determining factor of sleep feeling upon rising.

PMID- 9628130
TI  - An attempt of radar chart expression of a self-rating scale for sleep
      disturbance.
AB  - We made an attempt to express a complaint of sleep disturbance by a self-rating
      scale of radar chart mode. The questionnaire for sleep disturbance is made up of
      eight items. Each item was scored from grade 1 to 4. The score of each item was
      projected to the MY radar chart, designed by us. It is noted that this method is
      useful in following the effect of hypnotics on sleep disturbance.

PMID- 9628131
TI  - Evaluation of sleep using ambulatory skin potential recording: differences
      between morning and evening type.
AB  - In order to validate the evaluation of sleep using cassette type ambulatory skin
      potential measurement system (C-SPA), sleep duration variables extracted from 24
      h recordings were compared between two groups (16 of the intermediate type and 16
      of the evening type) with different sleep-wake habits rated by Morningness and
      Eveningness Questionnaires (MEQ). Compared with the intermediate type, the
      evening type subjects go to bed and get up later, have difficulty in falling
      asleep and more frequently awaken during sleep. Thus, the sleep variables by C
      SPA provide valuable information about duration of sleep and differentiate the
      sleep-wake habits.

PMID- 9628132
TI  - Development of an analysis system for 24-hour blood pressure and heart rate
      variability in the rat.
AB  - We have developed a system to evaluate 24-h changes of heart rate (HR) and blood
      pressure variability (BPV) in free moving rat. As a sensor to monitor
      electrocardiogram, we used the telemetry system. Analog data were sent to an
      analog to digital converter directly. The data were digitized at a sampling
      frequency of 1250 Hz and digitally stored on a computer. RR-intervals (difference
      of successive RR in electrocardiogram) were calculated using custom designed
      programs. Circadian change of the blood pressure and heart rate variability were
      calculated. We suggest that the system is a powerful tool in the evaluation of
      circadian changes of hemodynamics and autonomic nervous function in free moving
      rats.

PMID- 9628133
TI  - Cerebral blood volume in the sleep measured by near-infrared spectroscopy.
AB  - We investigated the relationship between hemodynamic changes in the cortex
      measured by near-infrared spectroscopy (NIRS) and the polysomnographic changes
      during sleep. Four healthy male volunteers participated in the study. Near
      infrared spectroscopy measuring and polysomnographic recordings were done
      simultaneously during sleep. In many case, oxy-hemoglobin (oxy-Hb) decreased and
      deoxy-hemoglobin (deoxy-Hb) increased during the transition from wakefulness to
      sleep, and oxy-Hb increased toward deep sleep. Oxy-Hb and deoxy-Hb had larger
      fluctuations during REM sleep than those during non-REM sleep. During REM sleep,
      oxy-Hb often showed a lower level and deoxy-Hb showed a higher level than those
      during the preceding and following non-REM sleep.

PMID- 9628134
TI  - Diurnal variation in baseline heart rate of anencephalic fetuses.
AB  - The diurnal change in baseline fetal heart rate (FHR) of four anencephalic
      fetuses at 20, 23, 24 and 30 weeks of gestation were examined. The mean baseline
      FHR in 00.00-06.00 h, 06.00-12.00 h, 12.00-18.00 h and 18.00-24.00 h were
      compared by one-factor ANOVA and Scheffe's test in each case. The diurnal
      variations in baseline FHR were recognized in all subjects (P < 0.01). In 3/4
      subjects, the lowest values were at 00.00-06.00 h. The diurnal variation in
      baseline FHR might be caused by maternal factors because it was present even in
      the anencephalic fetuses that had no central nervous system having the
      oscillators of the circadian rhythm.

PMID- 9628135
TI  - Cross-correlation between 1/f-like fluctuations in heartbeat and diurnal changes
      in the sleep-waking stage.
AB  - The cross-correlation function between diurnal changes in 1/f-like fluctuations
      of the R-R interval and those of the sleep-waking stage was calculated based on
      the data from six normal subjects in order to investigate the interactions among
      circadian components. Sleep stage was scored according to the standard criteria
      and waking stage was scored with criteria developed for the present study.
      Polysomnography was performed for 11 h during the daytime. The equation for 1/f
      was approximated using the power spectra of the R-R interval every 10 min. Cross
      correlation analysis between sleep-waking stage and 1/f fluctuation of the R-R
      interval suggested that the neural network for 1/f fluctuation in heartbeat is
      influenced by the sleep-wake cycle with a time lag in the order of tens of
      minutes.

PMID- 9628137
TI  - A longitudinal study of the development of daytime sleepiness in children.
AB  - This study aims to (i) investigate longitudinally developmental changes of
      diurnal variations of body temperature and sleepiness in preschool and school-age
      children and (ii) investigate the effect of acute 2 h sleep reduction on daytime
      sleepiness over a 3 year period. Three subjects were evaluated over three
      consecutive days: two control days and one 2 h sleep reduction day. A sleep
      latency test was conducted five times each day at 2 h intervals from 10.00 h, and
      oral temperature measured every hour. The results showed that (i) daytime
      sleepiness was high and decreased with increasing age, (ii) an afternoon dip
      occurred with pubertal development, (iii) effects of sleep loss generally
      increased daytime sleepiness, in particular at 10.00 h, and (iv) temperature
      acrophase was delayed with age.

PMID- 9628136
TI  - Video analysis of gross body movements during sleep.
AB  - Gross body movements (GM) during sleep, classified into four GM types by the
      involved parts of body, were evaluated using two-dimensional video analysis in
      five normal children aged 4-12 years. The rate of occurrence of all GM types
      showed apparent sleep stage dependency. Among four GM types, GM-1 (GM with axial
      rotation) was the most frequent. Averaged duration of GM-1 was the longest. A
      total of 77.2% of GM-1 started with the contraction of chin muscle and 35% of
      total sleep changes (tSC) were related to GM. A total of 5.6% of tSC following GM
      shifted to the deeper stage. Further evaluation is necessary in order to
      understand the physiological mechanism of GM.

PMID- 9628138
TI  - Sleep-wake rhythm of autistic children.
AB  - Using a sleep log for 28 days in the summer vacation, 89 autistic children living
      in a suburb of Tokyo were examined. Only one girl of 13 years showed a tendency
      of non-24 h sleep-wake syndrome. Most autistic children showed a large variation
      of total sleep time. Forty per cent of subjects showed 10% or more on coefficient
      of variation of total sleep time. In the retiring and rising time, many subjects
      tended to show late retiring and early rising.

PMID- 9628139
TI  - Sleep disorder in children with autism.
AB  - Eighty-eight children with autism, living in a suburb of Tokyo, were examined by
      questionnaire from 21 July to 31 August. Experienced sleep disorders were
      observed in 56 children; 44 of whom had sleep disorders before 3 years old. The
      average age when sleep disorders were seen to have stopped was 5 years old. The
      most common problem was difficulty falling sleep (n=23), followed by frequent
      awakening during sleep time (n=19), then early morning awakening (n=11). Bed
      wetting was observed in 22 children.

PMID- 9628140
TI  - Effects of volitional lifestyle on sleep-life habits in the aged.
AB  - This study investigates the relationship between a volitional lifestyle and sleep
      life habits in the aged. High volitional group (HVG: n=45, 26 men and 19 women,
      mean age 73.0 years) and low-volitional group (LVG: n=45, 27 men and 18 women,
      mean age 72.2 years) were grouped using the scale of self-confidence. It was
      found that high volitional aged individuals had a relatively well structured
      sleep, and that most had become accustomed to taking an appetitive nap (an
      individual with a mean wake time shorter than the average) in the mid-afternoon
      without experiencing insomniac problems.

PMID- 9628141
TI  - Gender differences in self-evaluated sleep quality and activity of middle-aged
      and aged subjects.
AB  - In order to investigate the gender difference of sleep and activity in middle
      aged and aged individuals, home-based sleep was self-evaluated for sleep quality
      and activity for 5 nights in 20 healthy adults (50-76 years old; 11 women, nine
      men). There was no significant gender difference for subjective sleep quality.
      However, the activity level and movement index at night were significantly higher
      in men than in women, and the activity level during the day was significantly
      lower in men than in women. The objective sleep quality of men was significantly
      worse than that of women, however, subjective sleep quality does not differ.

PMID- 9628142
TI  - Gender differences in the sleep of middle-aged individuals.
AB  - The study was designed to investigate gender differences in the sleep-wake
      patterns of healthy middle-aged individuals in their home environment.
      Polysomnography showed that daytime napping was more common in men than in women.
      Men had lower sleep efficiency index and experienced more stage 1 sleep. Males
      had significantly less stages 3 + 4 sleep, less stage REM sleep, and more
      transitions to wake from REM sleep. Men could not maintain stage REM as well as
      women. This study indicates that the gender differences in the sleep-wake
      patterns have appeared in a group of middle-aged individuals.

PMID- 9628143
TI  - Correlation between daytime activities and night sleep of aged individuals
      estimated by wrist activity and sleep log.
AB  - The daytime and night-time activities in 15 aged subjects was studied using a
      wrist-worn activity device. A significant negative correlation between the amount
      of daytime and night-time activities was found (gamma=0.26, P < 0.01). There was
      a significant gender difference relating to the amount of daytime activity; women
      had significantly greater amount of daytime activity than did the men (P <
      0.001). These results suggest that aged people with higher daytime activity sleep
      better than those with lower daytime activity and that nocturnal sleep in women
      may be less disturbed.

PMID- 9628144
TI  - Relationship between nocturnal urinary frequency and sleep disturbances in aged
      men.
AB  - The relationship between nocturnal urinary frequency and sleep disturbances is
      investigated in aged men in 12 rural towns in Kyoto and Shiga Prefectures. The
      subjects were 178 men who did not have diseases or symptoms that were likely to
      affect urinary condition or sleep. There were no significant differences in sleep
      disturbances, except sleep maintenance, between the normal group (nocturnal
      urinary frequency below twice per night) and the abnormal group (nocturnal
      urinary frequency twice or more per night). In healthy aged men, nocturnal
      urinary frequency only caused disturbance in sleep maintenance, but did not cause
      any other sleep disturbance.

PMID- 9628145
TI  - Sleep problems in the aged in relation to senility.
AB  - As a part of an epidemiologic survey of dementia in a community of aged persons,
      correlation between sleep complaints and physical illness and senility were
      studied. A total of 3302 randomly sampled aged individuals(aged > or = 65 years)
      were studied using a questionnaire. In this sample the prevalence of poor sleep
      and habitual snoring did not increase with age. The prevalence of excessive
      daytime sleepiness showed an increase with age. Male predominance of habitual
      snoring and female predominance of poor sleep were observed. Female predominance
      of excessive daytime sleepiness was noted among the aged 70 and over. Age-related
      excessive daytime sleepiness was significantly correlated with senility.

PMID- 9628146
TI  - Periodic limb movements and sleep-wake disorder.
AB  - The relationship of periodic limb movements (PLM) and sleep-wake disorders in 11
      patients was investigated. Two patients complained of insomnia. A patient with
      cervical spinal canal stenosis had a complaint of difficulty in initiating sleep.
      Movement index (MI) was 51 and PLM arousal index was 8. A patient with chronic
      hemodialysis had a complaint of difficulty in initiating and maintaining sleep.
      MI was 79 and PLM arousal index was 51. One patient with myotonic dystrophy
      showed 79 in MI and 3 in PLM arousal index. It is suspected that myotonic
      dystrophy is less sensitive to stimuli during sleep (i.e. PLM). These results
      suggest that the sleep-wake disorders associated with PLM relate to the threshold
      of awakening.

PMID- 9628147
TI  - Sleep improvement by light in a demented aged individual.
AB  - We administered daily morning bright light exposure in two separate periods to a
      demented aged subject in a nursing home and analyzed the sleep pattern changes
      from the sleep diary over 6 months. In the first light exposure period, the ratio
      of sleep time in night hours increased and maintained a higher value throughout
      the period than the previous baseline. After stopping the light exposure, the
      sleep pattern of the subject deteriorated. Resuming the light exposure reproduced
      similar sleep pattern changes. These results suggest that morning bright light
      exposure provides a better environment for aged persons to maintain a regular
      sleep-wake pattern.

PMID- 9628148
TI  - Motor activity rhythm in dementia with delirium.
AB  - Using an actigraph, the activity patterns in 13 demented patients with delirium
      were examined. We analyzed the data of the eight patients, wearing the actigraphs
      for more than 10 days. They were classified into four types: type A, nocturnal
      delirium type; type B, wandering type; type C, hypobulia type; and type D, lying
      down type. The day to day activity variation was most prominent in type A and
      seemingly the least in type B. The dominant period of activity rhythm was nearly
      24 h in all cases. Additional 12-h period was observed in type C. Actigraphs
      might become useful in making therapeutic decisions regarding demented patients
      with delirium.

PMID- 9628149
TI  - Treatment of insomnia by concomitant therapy with Zopiclone and Aniracetam in
      patients with cerebral infarction, cerebroatrophy, Alzheimer's disease and
      Parkinson's disease.
AB  - For insomniac patients, sleeping drugs are used: in addition, concomitant therapy
      with other drugs has been tried in an effort to prevent a decrease in the effects
      due to long-term continuous use. This report presents the results of a study on
      the sleeping effects in nine aged patients with insomnia associated with
      cerebrovascular and noncerebrovascular disorders who received concomitant therapy
      with Zopiclone and Aniracetam. The treatment in 7/9 cases (78%) was found to be
      effective, showing more than 50% prolongation of sleeping time, and in two cases
      (22%) was found to be ineffective. We discuss the mechanism of action referring
      to the literature.

PMID- 9628150
TI  - A case of insufficient sleep syndrome.
AB  - All night polysomnographic evaluation (PSG) soon after admission and at the late
      period of admission revealed an atypically high sleep efficiency and a prolonged
      total sleep time. Sleep onset latency and distribution of REM and NREM sleep
      stages were like those of normal sleepers. On REM latency, while it was
      remarkably reduced (25.0 min) soon after admission and sleep onset REM period
      (SOREMP) was found, at the late period of admission it was prolonged and SOREMP
      was not found. Giving multiple sleep latency test with polysomnography, soon
      after admission subjective excessive daytime sleepiness had already improved and
      mean sleep latency (13.2 min) was within normal range. However, SOREMP appeared
      twice in five tests. We considered that the appearance at the early period of
      admission was the result of REM pressure growing.

PMID- 9628151
TI  - Sleep behavior of pregnant women using sleep log.
AB  - Sleep log study, which was designed to study sleep characteristics by
      questionnaire, was performed on 172 pregnant women about the relationship between
      their pregnancy and their night sleep. Sleep behavior by sleep log revealed that
      they woke more frequently during the course of their pregnancy and that their
      total sleep time decreased gradually toward the end of their pregnancy. According
      to their subjective evaluations, these shortages of night sleep could not be made
      up with the morning naps in the multiparas as was the case of the primiparas.
      These changes in sleep characteristics have been studied from biological,
      psychological and social factors view points.

PMID- 9628152
TI  - The effects of a 20-min nap before post-lunch dip.
AB  - The effects of a 20-min nap before post-lunch dip were studied. The subjects
      participated in nap and no-nap conditions at intervals of 1 week. Their
      electroencephalogram (EEG) recordings of relaxed wakefulness, mood, performance,
      and self-rating of performance level were measured every 20 min from 10.00 to
      18.00 h. For nap condition, the subjects went to bed at 12.20 h and were awakened
      after they slept for 20 min. The nap improved subjective sleepiness and self
      rating of task performance, and suppressed EEG alpha activity. The results
      suggest a positive effect of a 20-min nap upon the maintenance of daytime arousal
      level.

PMID- 9628153
TI  - Prolonged polysomnography in a case with recurrent hypersomnia.
AB  - An 18-year-old male patient with recurrent hypersomnia (RH) was evaluated using
      prolonged polysomnography (PSG). During symptomatic period (SMP), the patient
      showed both 'dissociated stage REM' (DREM), REM sleep without muscle atonia and
      'dissociated stage 1' (DSt-1), and stage 1 sleep with rapid eye movement. These
      stages were observed in the morning or following daytime record. They decreased
      during asymptomatic period (ASMP). It has been said that RH is caused by
      dysfunction of the hypothalamus and midbrain limbic system. The present result
      suggests also that RH involves dysfunction of the brain stem.

PMID- 9628154
TI  - A case of subwakefulness syndrome.
AB  - We report a patient, a 30-year-old male Japanese-Brazilian migrant construction
      worker, suffering from excessive daytime sleepiness for at least 6 months.
      Electroencephalogram recordings during his waking states showed that 10-Hz and 60
      microV alpha activity was present prominently in the occipital regions. From the
      multiple sleep latency test, it was found that stages 1-2 NREM sleep episodes
      appeared repetitively without any REM episodes, and that the mean sleep latency
      was 10.2 min. These findings support the diagnosis that this patient suffers from
      subwakefulness syndrome.

PMID- 9628155
TI  - Night-time hypnopompic visual hallucinations related to REM sleep disorder.
AB  - We encountered three patients who had experienced hypnopompic visual night-time
      hallucinations. Their clinical manifestations resembled Charles Bonnet's syndrome
      and the content of their experiences were understood as attempts at wish
      fulfillment. However, abnormal REM findings were recognized on polysomnogram at
      the occurrence of visual hallucination in two cases. We speculated that
      dysfunction of REM sleep mechanism might contribute to the night-time occurrence
      of such kind of visual hallucination and that their visual experiences might be
      reflected by dream content.

PMID- 9628156
TI  - An animal model for pregnancy-associated sleep disorder.
AB  - We studied basic sleep changes in pregnant rats in order to understand how
      pregnancy alters sleep. In the rat, pregnancy increased nocturnal nonREM sleep
      across the entire period but increased REM sleep only in the early period. By the
      end of pregnancy, diurnal sleep was decreased, showing that pregnancy in rats
      causes biphasic sleep changes as it does in humans. Termination of pregnancy
      returned the enhanced sleep to baseline as in the estrous cycle. Therefore,
      significant changes in the pattern of sleep occurred during pregnancy in rats,
      suggesting that the animal model may contribute to understanding the mechanism of
      sleep disorders related to human pregnancy.

PMID- 9628157
TI  - Usefulness of arousal for the diagnosis of sleep breathing disorder.
AB  - We hypothesize that breathing disorder related arousal index (B-ArI) can
      differentiate sleep breathing disorder from simple snorer when apnea hypopnea
      index (AHI) is low. We studied 54 patients using polysomnography. Breathing
      disorder related arousal (B-Ar) was defined as arousal accompanied by apnea,
      hypopnea, desaturation or snort. Mean AHI was 44.2+/-34.0/h, and B-ArI correlated
      significantly with AHI, desaturation index, percentage total sleep time with SpO2
      below 90%. Breathing disorder related arousal index was greater than AHI when AHI
      was below 20. In 11/54 patients, AHI was below 10, and B-ArI more than 10. Nasal
      continuous positive airway pressure was applied to six patients and showed
      reduced B-ArI. Breathing disorder related arousal index may be one of the useful
      indices for the diagnosis of sleep breathing disorder when AHI is less than 10.

PMID- 9628158
TI  - A case of Arnold-Chiari Type I malformation presenting with dysrhythmic breathing
      during sleep.
AB  - A 43-year-old woman presented with dull headache, left tinnitus and dizziness.
      Neurological examination revealed down-beat gaze nystagmus, left tinnitus,
      positive Romberg sign, poor standing on the left foot, poor tandem gait, left
      spastic gait and positive pathological reflexes in the bilateral upper and lower
      extremities. Plain X-ray of the skull and cervical vertebrae demonstrated basilar
      impression and atlantoaxial fusion. Magnetic resonance imaging of the brain and
      cervical spine showed cerebellar tonsil descent and syringomyelia located in the
      left side of the spine at the II-III vertebral level which communicated with the
      fourth ventricle. The patient was diagnosed as having cervical syringomyelia.
      Arnold-Chiari type I malformation and basilar impression. Preoperative
      polysomnography showed dysrhythmic breathing and bradypnea during sleep. Abnormal
      breathing improved after suboccipital decompression craniotomy and upper cervical
      laminectomy. It was suggested that dysrhythmic breathing was caused by a disorder
      of the medullary respiratory center. Herniation of the cerebellar tonsil and
      syringomyelia might have compressed the medulla.

PMID- 9628159
TI  - Alteration of esophageal pressure in sleep-disordered breathing.
AB  - We investigated the alteration of esophageal pressure (Pes) in 10 patients with
      upper-airway sleep-disordered breathing (UASDB) and the relationship among Pes,
      breathing patterns and EEG arousals. Increased negative Pes without apnea or
      hypopnea, appeared not only in upper airway resistance syndrome but also in
      obstructive sleep apnea syndrome. This phenomenon produced frequent EEG
      microarousals leading to sleep fragmentation and daytime sleepiness. Moreover,
      increased negative Pes occasionally continued for more than 20 min without an EEG
      arousal, which might be considered to be one of the factors to cause
      complications of UASDB.

PMID- 9628160
TI  - Differences in arousal response between aged and middle-aged patients with
      obstructive sleep apnea syndrome.
AB  - The aim of this study is to show the clinical significance of the differences in
      arousal response at a termination of apnea/hypopnea between aged and middle-aged
      patients with obstructive sleep apnea syndrome (OSAS). We polygraphically
      assessed electrocardiographic (ECG) and electroencephalographic (EEG) arousal.
      Electrocardiographic arousal was defined as an abrupt increase in heart rate at a
      termination of apnea/hypopnea. Our findings showed that EEG and ECG arousal at a
      termination of apnea/hypopnea were significantly suppressed in aged patients with
      OSAS, which might provide useful information on the pathophysiology, of OSAS.

PMID- 9628161
TI  - Prevalence of ischemic heart disease among patients with sleep apnea syndrome.
AB  - We investigated the prevalence of ischemic heart disease (IHD) in sleep apnea
      syndrome (SAS) and the presence of coronary risk factors involved in the onset of
      IHD in 386 subjects with suspected SAS due to heavy snoring. The prevalence of
      IHD among patients with untreated SAS was found to be 23.8%, and the percentage
      of patients having SAS complicated with IHD was high among those with moderate or
      severe SAS. Sleep apnea syndrome patients with IHD also showed high prevalences
      of hypertension and hyperlipidemia. It appears that sleep apnea aggravates the
      factors that cause coronary vascular disorders, and is involved in the onset of
      IHD.

PMID- 9628162
TI  - Daytime sleepiness and automobile accidents in patients with obstructive sleep
      apnea syndrome.
AB  - We evaluated the rate of automobile accidents and daytime sleepiness using the
      Epworth sleepiness scale (ESS) in 44 patients with obstructive sleep apnea
      syndrome (OSAS). We defined the automobile accident score as a sum of two points
      for every one automobile accident and one point for every near-miss accident.
      Automobile accidents and near-misses were found in 54.5% and 50.0% in patients
      with OSAS. Automobile accident score was significantly correlated with the ESS
      score (r=0.56, P < 0.01). Our findings suggest that ESS score may be useful in
      detecting patients with the potential risk of automobile accidents associated
      with daytime sleepiness.

PMID- 9628163
TI  - Effectiveness of tonsillectomy in adult sleep apnea syndrome.
AB  - Tonsillectomy was performed on 10 adult sleep apnea patients (five males, five
      females; average age, 39 years old; average body mass index, 24.8 kg/m2).
      Tonsillectomy alone was indicated if tonsillar hypertrophy was moderate to severe
      and the length of the soft palate was less than 35 mm according to cephalometry.
      Remarkable improvements were observed in all cases following surgery. The average
      weight of the resected tonsils was 11 g. The patients demonstrated a preoperative
      apnea + hypopnea index (AHI) of 14.4/h. This decreased to 2.9/h postoperatively.
      The intraesophageal pressure change improved from -36.6 to -15.7 cmH2O following
      surgery. A significant correlation between preoperative AHI and the degree of
      obesity (r=0.684, P < 0.05) was found. Although uvulopalatopharyngoplasty has
      been used extensively to treat sleep apnea, the present results suggests that
      certain subjects can be effectively treated through only tonsillectomy.

PMID- 9628164
TI  - Changes in work performances in obstructive sleep apnea patients after dental
      appliance therapy.
AB  - The effects of dental appliances on work performances of obstructive sleep apnea
      syndrome (OSAS) is not well examined. This study evaluated the polysomnographic
      and psychological findings before and after therapy. Nine patients were diagnosed
      OSAS by nocturnal polysomnography. The psychological batter, was performed from
      13:00 to 14:00, which consisted of Uchida-Kraepelin psychodiagnostic test (U-K's
      test) and Bourdon's cancellation test (Bourdon's test). Approximately 3 months
      after the treatment, the examinations were performed. Apnea and desaturation
      index decreased significantly after the therapy. In addition, sleep architecture
      improved after the therapy compared with that before the therapy. Dysfunction of
      task performances, such as mean level of work amounts in U-K's test, mean error,
      mean performance time and mean deviation in Bourdon's test improved after
      therapy. We conclude that dental appliances therapy is effective not only to
      apnea but also to work performance in OSAS.

PMID- 9628165
TI  - Effectiveness of prosthetic mandibular advancement for obstructive sleep apnea:
      analysis by sleep position.
AB  - Fifteen patients with obstructive sleep apnea were treated using prosthetic
      mandibular advancement (PMA). Each patient was evaluated in the supine and
      lateral decubitus positions with and without PMA. After PMA treatment, the mean
      intraesophageal pressure (Peso) in the supine position improved from -42.6 to 
      27.3 cmH2O and the mean apnea + hypopnea index (AHI) decreased from 48.8/h to
      23.7/h. The mean Peso in the lateral decubitus position improved from -27.9 to 
      18.6 cmH2O and the mean AHI decreased from 9.6/h to 6.6/h. With PMA, respiratory,
      disturbance during sleep further improved by changing the body position from the
      supine to lateral decubitus position.

PMID- 9628166
TI  - Mechanism of action and therapeutic indication of prosthetic mandibular
      advancement in obstructive sleep apnea syndrome.
AB  - Prosthetic mandibular advancement (PMA) was applied to nine patients with
      obstructive sleep apnea syndrome (OSAS) and its therapeutic usefulness, mechanism
      of action, and clinical indication were discussed based on polysomnographic
      findings and serial examination of upper airway before and during PMA treatment.
      Apnea hypopnea index significantly decreased during PMA treatment compared with
      the value before treatment (P < 0.01) and the rate of the treatment responder
      counted 78.1%. Cephalometric variables indicated forward and inferior advancement
      of mandible in our subjects. Magnetic resonance imaging of the upper airway
      during sleep revealed a marked improvement of velophanryngeal obstruction in most
      subjects. In addition, intraesophageal negative pressure during sleep decreased
      significantly. Our results confirmed the high therapeutic efficacy of PMA for
      OSAS and indicated forward advancement of the mandible and decrease of negative
      pressure loading on upper airway with PMA might suppress velopharyngeal collapse.
      Thus, PMA was regarded as one of the treatments of choice for OSAS occurring
      based on with velopharyngeal narrowing.

PMID- 9628167
TI  - Prevalence of sleep-related respiratory disorders in 101 schizophrenic
      inpatients.
AB  - We studied the prevalence of sleep-related respiratory disorders (SRRD) in 101
      schizophrenic inpatients (64 men and 37 women) and in 48 healthy volunteers
      (control group: 22 men and 26 women) using ambulatory pulse-oximetric devices.
      Those with a desaturation index (DI) > or = 5 were classified as having SRRD. The
      prevalence of SRRD in the schizophrenic patients (men 21.9%, women 13.5%) was not
      higher than that in the control group (men 30.7%, women 13.6%). Gender difference
      in the prevalence of SRRD was not observed in schizophrenic group. This was
      probably because the schizophrenic women took an increased amount of sleeping
      pills. Neuroleptics were shown to be least effected on SRRD.

PMID- 9628168
TI  - Two cases of sleep-disordered breathing in climacteric.
AB  - Two cases of sleep disordered-breathing in climacteric were reported.
      Polysomnography including esophageal pressure (Pes) measurement was performed.
      Case 1 was diagnosed as upper airway resistance syndrome. Case 2 was diagnosed as
      obstructive sleep apnea syndrome, while many episodes of upper airway resistance
      also existed. Hormone replacement therapy improved clinical symptoms, and in case
      1, Pes nadir was improved but incidence of arousals which was induced by
      breathing disturbances was not significantly changed. Sleep disordered-breathing
      should be suspected as a cause of sleep disorder even in females, especially in
      climacteric age. Pes measurement and evaluation of arousals is required. Hormone
      replacement therapy may release the upper airway resistance.

PMID- 9628169
TI  - Sleep-disordered breathing in a patient with congenital myopathy.
AB  - A case of adult onset myopathy who showed a peculiar sleep-related respiratory
      disorder (SRRD) is reported. She recovered from respiratory failure after
      tracheostomy and/or with the aid of the respirator used only during the night.
      Sleep study without the use of respirator revealed that her sleep was highly
      fragmented by frequent arousal responses due to inspiratory effort but not by
      apnea or hypopnea. To our knowledge this type of SRRD has not been described.

PMID- 9628170
TI  - Clinical characteristics of circadian rhythm sleep disorders.
AB  - From our practice at the sleep disorders clinic in Kohnodai Hospital, National
      Center of Neurology and Psychiatry (NCNP), we report the clinical characteristics
      of circadian sleep-wake rhythm disorders. Nearly 90% of circadian rhythm sleep
      disorders were diagnosed as delayed sleep phase syndrome (DSPS) or as non-24
      sleep-wake syndrome (non-24). While DSPS was equally common in males and females,
      non-24 was more frequently seen in men. It was of psychiatric interest that a
      considerable number of patients had depressive states in the course of their
      circadian rhythm sleep disorders. Difficulty in adapting to social life was more
      severe in patients with non-24 than in those with DSPS.

PMID- 9628171
TI  - Continuous measurement of temperature in non-24 hour sleep-wake syndrome.
AB  - The onset of the low temperature (LT) zone which was defined as a period when the
      rectal temperature was below its daily mean is a convenient circadian phase
      marker. In this study, we document three cases of non-24 h sleep-wake syndrome in
      which identification of the LT zone as an evening circadian phase marker
      contributed to clinical judgments. We found that the LT zone was correlated well
      with dim light melatonin onset. Moreover, calculating the LT zone was useful in
      determining phase position in irregular sleep pattern and in determining the
      timing of bright light therapy.

PMID- 9628172
TI  - Circadian rhythms of hormone concentrations in alcohol withdrawal.
AB  - We investigated the circadian rhythm of hormones (cortisol, melatonin) in
      alcoholic patients during and 1 month after alcohol withdrawal. Patients with
      delirium tremens had irregular serum hormone concentration rhythms during
      withdrawal, which normalized after the withdrawal period. Patients without
      delirium tremens had normal circadian rhythms even during the withdrawal period.
      We speculated that the disturbance of the biological oscillator, in terms of the
      decline of synchronizing function or the decrease in synchronizing factors,
      caused abnormal circadian rhythms of hormone release during delirium tremens.

PMID- 9628173
TI  - Human time production under constant routine.
AB  - Previous reports have suggested that human time production of several seconds
      fluctuates across the day. In order to test whether human time production was
      controlled by the circadian process or by the homeostatic process, we investigate
      diurnal fluctuation of human time production under constant routine conditions.
      We found a common circadian feature in time production tests of 10 s by
      calculating Z-score for each subject; afternoon troughs and morning peaks. These
      results may suggest that human time production was modulated by the circadian
      process.

PMID- 9628174
TI  - Twenty-four hour profiles of four hormones under constant routine.
AB  - We studied the circadian features of melatonin, cortisol, thyroid stimulating
      hormone (TSH), and growth hormone (GH) together with rectal temperature during 36
      h continuous forced wakefulness without physical exercise under dim light
      condition (constant routine). Subjects consisted of four healthy men aged 22-24
      years. Blood sampling was conducted hourly, and food and water were supplied bi
      hourly during the constant routine. Melatonin, TSH and cortisol displayed clear
      circadian rhythms under constant routine condition. While GH secretion was
      unlikely to be driven solely by the circadian pacemaker, its suppression round BT
      nadir may indicate that GH secretion was modulated to some extent by circadian
      rhythm.

PMID- 9628175
TI  - Core temperature pattern and self-rated lifestyle.
AB  - We investigated the relationship between a subject's self-rated lifestyle and
      their pattern of nocturnal rectal temperature. Fifty-five students participated
      in the study. Among several significant findings, irregularity and eveningness
      component of lifestyle (irregular and delayed sleep phase) showed a significant
      negative correlation with temperature at the morning rising time. Examination of
      the nocturnal temperature pattern revealed that rectal temperature stayed at its
      lowest level in the early morning hours in the subjects with irregular and
      eveningness-like lifestyles.

PMID- 9628176
TI  - Effects of aging on morningness-eveningness and sleep habits in Korean and
      Japanese workers.
AB  - The Morningness-Eveningness Questionnaire and Life Habits Inventory were given to
      Korean and Japanese workers. The distributions of scores on the questionnaire for
      these two groups were normal and its mean slightly moved to the Morning type with
      aging. It is noteworthy, however, that the mean scores of Korean workers was
      lower than those of the Japanese workers. The self-reported waking times and
      bedtimes for the two groups gradually became earlier with aging. From these
      results it could be said that aging was an factor that led to the difference of
      circadian phase.

PMID- 9628177
TI  - Effects of the gradually increasing dawn light stimulation on sleep feeling.
AB  - Effects of a new lighting stimulation system upon subjective sleep and waking
      feeling were psychophysiologically examined in 24 healthy students in order to
      develop a way of obtaining comfortable awakening. The subjects underwent three
      different experimental conditions: the light stimulation condition, non-light
      stimulation condition and the control condition. The satisfaction of sleep was
      higher and day sleepiness lower in the light condition compared with the other
      two conditions. Subjective fatigue related to mental functions at waking was also
      smaller in the light condition compared with the other two conditions. These
      results suggest that the improvement of sleep feeling and waking seems to be
      achieved by gradual increased dawn light stimulation.

PMID- 9628178
TI  - Effects of evening light on body temperature.
AB  - Six healthy male subjects aged 21-35 years participated in the present study. The
      subjects were exposed to dim light (150 lux) or bright light (3000 lux) at eye
      level, from 19.00 to 21.30 h for 5 days. Rectal temperature and wrist activity
      were monitored throughout the study period. Rectal temperature nadir was delayed
      significantly after the bright light exposure. Ease in sleep initiation and
      overall sleep quality, measured by questionnaire, were aggravated significantly
      by the evening bright light exposure. These results suggest that strong
      illumination at night may disturb nocturnal sleep.

PMID- 9628179
TI  - Effects of short duration morning bright light in healthy elderly subjects. I:
      subjective feeling and ophthalmological examinations.
AB  - Seven aged subjects aged 61-78 years were exposed to 6000 lx bright light for 30
      min during morning hours at their homes for 1 week. Visual analog scale was
      recorded before bedtime and after rising to assess subjective feelings.
      Ophthalmological examinations were made before and after light exposure, to
      exclude pre-existing ocular disorders and to detect ocular damage. Furthermore,
      ocular fatigue was self-evaluated immediately before and after exposure. Visual
      analog scale results indicated that alertness reduced significantly before
      bedtime. Ophthalmological abnormalities were not found after exposure. These
      findings suggest that short duration morning bright light exposure reduces night
      time vigilance.

PMID- 9628180
TI  - Effects of short duration morning bright light in healthy elderly. II: sleep and
      motor activity.
AB  - Subjective sleep feelings and motor activity were measured in seven healthy
      elderly subjects for 6 days. The subjects were exposed to bright light (6000 lux)
      for 30 min in the morning or instructed to sit in front of a desktop lighting
      device without light. The average level of motor activity during the night was
      significantly decreased in the bright light condition, compared with the
      controlled condition. However, daytime motor activity did not show significant
      differences between the two conditions. From these findings, even a short
      duration of morning bright light is effective in maintaining sleep without
      changing daytime activity.

PMID- 9628181
TI  - An activity monitor study on the sleep-wake rhythm of healthy aged people
      residing in their homes.
AB  - The aim of this preliminary study was to investigate sleep-wake rhythm in active,
      healthy elderly people residing in their usual habitat. The subjects were thirty
      five male volunteers within an age range of 65-95 for 3-4 days. We measured the
      sleep-wake rhythm of the subjects with an Actillume which is a combined wrist
      activity monitor and illumination recorder. Analysis of the Actillume recording
      showed that 24 of the 35 subjects (69%) kept continuous activity indicating good
      maintenance of wakefulness with high light exposure. The mean mesor of sleep-wake
      rhythm, however, significantly decreased in the older subjects (aged 80-95;
      n=15).

PMID- 9628182
TI  - Polysomnography and body temperature changes by phototherapy in a delayed sleep
      phase syndrome case.
AB  - We examined polysomnography (PSG) and body temperature in a patient with delayed
      sleep phase syndrome who responded to phototherapy. The patient was a 31-year-old
      woman whose condition had slightly improved by a vitamin B12 administration.
      Phototherapy was administered to her in combination with the vitamin B12
      medication, and this combined treatment successfully advanced her delayed sleep
      phase. On PSG, the regimen showed shortened sleep latency, decreased total sleep
      time and stages 1 and 2 sleep, and increased slow wave sleep. Phototherapy also
      improved temporal distribution of delta half-waves (0.5-2.0 Hz, > or = 31 microV)
      as well as phase relationship between sleep and body temperature.

PMID- 9628183
TI  - Wrist activity rhythm and sleep diary of delayed sleep phase syndrome.
AB  - Wrist activity rhythm and sleep diary data in a case of delayed sleep phase
      syndrome were investigated. The sleep self-estimation was nearly compatible with
      the activity levels of the actigraph. The actigraphic data were also analyzed.
      The subject's most fixed period of activity was 24.31 h, and acrophase (time of
      day) that fixed the data to a 24 h period was 03.25 h. The subject has had
      reversed night and day sleep patterns for more than 7 years. It was very
      difficult to advance the sleep phase when the delayed phase has been continuous
      long-term under the state of poor social cues.

PMID- 9628184
TI  - Melatonin treatment for circadian rhythm sleep disorders.
AB  - We administered 1-3 mg melatonin to 11 patients (eight men, three women, aged 16
      46 years) with circadian rhythm sleep disorders; nine with delayed sleep phase
      syndrome and two with non-24-hour sleep-wake syndrome. Sleep logs were recorded
      throughout the study periods and actigraph and rectal temperature were monitored
      during treatment periods. Melatonin was administered 1-2 h before the desirable
      bedtime for expected phase-shifting, or 0.5-1 h before habitual bedtime for
      gradual advance expecting an hypnotic effect of the melatonin. Melatonin
      treatments were successful in 6/11 patients. Timing and dose of melatonin
      administration, together with its pharmacological properties for circadian rhythm
      sleep disorders, should be further studied.

PMID- 9628185
TI  - Trials of bright light exposure and melatonin administration in a patient with
      non-24 hour sleep-wake syndrome.
AB  - We report a patient with non-24 h sleep-wake syndrome (non-24) whose free-running
      sleep-wake cycle was successfully treated with both scheduled bright light
      exposure and melatonin treatment. In the present study, morning bright light as
      well as evening melatonin phase-advanced sleep-wake cycles and melatonin rhythm.
      Both these procedures achieved appropriate entrainment to a 24 h day. However,
      the patient did not continue morning bright light therapy after the discharge.
      Rising at appropriate times in the morning for bright light therapy was difficult
      for him to continue. Melatonin treatment was better tolerated because of its ease
      of application.

PMID- 9628186
TI  - Melatonin treatment for rhythm disorder.
AB  - We tried melatonin treatment in two patients with non-24 h sleep-wake syndrome,
      who did not respond to treatments by vitamin B12, bright light therapy, or
      hypnotics. In one patient, melatonin 5-10 mg improved difficulty in falling
      asleep and in waking, although it failed to improve the sleep-wake rhythm. In
      another patient, melatonin 3 mg successfully changed the sleep-wake rhythm from
      free-running pattern to delayed sleep phase pattern. However, melatonin re
      administration after a 4-month drug-free interval failed to improve his free
      running sleep-wake rhythm. These results suggest that melatonin acted as a sleep
      inducer in one patient and as a phase setter in the other, although the effect on
      the latter patient was transient.

PMID- 9628187
TI  - Free-running of plasma melatonin rhythm prior to full manifestation of a non-24
      hour sleep-wake syndrome.
AB  - A long-term observation of a sighted man who developed a non-24 h sleep-wake
      syndrome is reported. A partial entrainment was observed first, whereby the sleep
      wake rhythm was entrained by the day-night alternation whereas the circadian
      rhythm in plasma melatonin was free-running. Two years later, the sleep-wake
      rhythm of this subject started to free-run together with the melatonin rhythm.
      Oral administration of melatonin for 2 weeks improved the entrainability of both
      rhythms but failed to entrain the rhythms completely. It is concluded that the
      free-running of the circadian pacemaker preceded a full manifestation of a non-24
      h sleep-wake syndrome in this particular subject.

PMID- 9628188
TI  - Time course of saliva and serum melatonin levels after ingestion of melatonin.
AB  - Salival and serum melatonin levels after melatonin ingestion were measured by gas
      chromatography-mass spectrometry. Ingestion of 3 mg melatonin caused a marked
      increase in serum melatonin (3561+/-1201 pg/mL) within 20 min, followed by a
      gradual decrease, but the level still remained higher than the basal level at 240
      min after the ingestion. The saliva melatonin 60 min after the ingestion showed
      the highest level (1177+/-403 pg/mL) which was one-third of the plasma level. The
      saliva melatonin level was highly correlated with the serum level throughout the
      experimental period (r=0.82, P=0.0001). These data indicate that the measurement
      of saliva melatonin level may be a suitable indicator for the melatonin secretion
      into general circulation.

PMID- 9628189
TI  - Temporal lobe epilepsy in infants and children.
AB  - Temporal lobe epilepsy in adults and adolescents is a fairly homogeneous
      syndrome, both in terms of seizure semiology and in terms of its pathology, and
      it has been studied extensively. Temporal lobe epilepsy in infants and young
      children has begun to receive increasing attention in recent years, and a
      different clinico-pathological picture has emerged. Clinically, the concept of
      complex partial seizures, which may be useful in adults, is difficult to apply to
      infants, since it is often not possible to assess impairment of consciousness in
      this age group. The main distinctive features of complex partial seizures of
      temporal lobe origin in infants are (1) a predominance of behavioral arrest with
      possible impairment of consciousness, (2) no identifiable aura, (3) automatisms
      that are discrete and mostly orofacial, (4) more prominent convulsive activity,
      and (5) a longer duration (more than 1 min). In addition, seizures of temporal
      lobe origin in infants may appear clinically generalized, such as infantile
      spasms or generalized tonic seizures, or can occasionally represent a benign
      syndrome. The neuropathological findings of temporal lobe epilepsy in infants
      differ even more than the clinical seizure semiology. In contrast to adult and
      adolescent patients, mesial temporal sclerosis is a rare finding in infants, in
      whom the pathological abnormalities associated with seizures of temporal lobe
      origin consist mostly of dysplasias, migrational disorders, hamartomas, and low
      grade tumors such as gangliogliomas. Mesial temporal sclerosis is seen more often
      in older children than in infants, and its pathogenesis remains a subject of
      controversy.

PMID- 9628190
TI  - Megalencephaly and leukodystrophy with mild clinical course: a report on 12 new
      cases.
AB  - Twelve patients with early infancy onset megalencephaly and leukodystrophy with a
      mild clinical course are reported. The neuroradiological, clinical, and genetic
      aspects of this recently recognized familial leukodystrophy syndrome were
      reviewed. Five were affected siblings, and all patients had consanguineous
      parents. Macrocephaly, a slowly progressive delay in motor development and mild
      mental deterioration constitute the clinical triad of the disease, showing
      characteristic age-related onset. The clinical findings outlined remarkably
      slight functional deterioration despite severe lesions on magnetic resonance
      imaging (MRI), especially in the initial period. Characteristically, mental
      function is preserved for years after onset of the motor deficit. The MRI lesions
      do not reflect the progress of disease. The disease probably has an autosomal
      recessive mode of inheritance even though no metabolic defect has been detected
      to date. In a more severe variant of the mentioned disease, there is more
      progressive and severe neurological dysfunction, including ataxia and spastic
      quadriparesis, leading to an inability to walk independently after 10 years of
      age. In mild variants, however, disease severity varies from macrocephaly with
      near-normal pyschomotor development to mild motor and/or mental dysfunction.
      Seizures were observed in both types but response to drugs was good. The 12
      patients reported here confirm the specific and distinguishing clinical and
      radiological features of the previously reported 51 cases with this new syndrome,
      while adding some information regarding identification of the disease.

PMID- 9628191
TI  - Study on surgical treatment of intractable childhood epilepsy.
AB  - We studied the clinical details of 14 children with intractable epilepsies, all
      of whom underwent epilepsy surgery before age 18 years. All 14 suffered
      catastrophic seizures, which were resistant to the full range of available
      medical treatments. The ages at operation ranged from 4 years 7 months to 17
      years 2 months, with a mean of 9 years 11 months. In nine patients, the age at
      onset of epilepsy was less than 2 years. The seizure disorders were classified as
      temporal lobe epilepsy in two patients, extratemporal lobe epilepsy in 10, and
      symptomatic generalized epilepsy in two. Eight patients had a hemicorporeal
      deficit (hemiparesis or hemiplegia) preoperatively. All 14 patients showed
      localized magnetic resonance imaging (MRI), single photon emission computer
      tomography (SPECT) and/or positron emission tomography (PET) abnormalities,
      providing crucial information regarding the epileptic focus. As to the surgical
      outcomes, four patients became seizure-free and the other 10 showed significant
      improvement during a mean follow-up period of 2 years 5 months. As to etiology,
      cortical dysplasia was identified in seven patients. Epilepsy surgery should be
      considered for intractable childhood epilepsy based on individual clinical
      characteristics, including seizure status, cognitive development, and evidence
      indicating location of the seizure focus, rather than age.

PMID- 9628192
TI  - Dystrophin gene analysis on 130 patients with Duchenne muscular dystrophy with a
      special reference to muscle mRNA analysis.
AB  - On dystrophin gene analysis by multiplex polymerase chain reaction (PCR), 76 of
      130 (58.5%) Japanese patients with Duchenne muscular dystrophy had a deletion or
      duplication in genomic DNA. Of the remaining 54 patients who had no identifiable
      gene mutations, muscle biopsy tissue was available in 16 for RNA extraction. The
      full length of the coding regions of dystrophin cDNA was amplified in 10
      fragments by reverse transcription nested PCR (RT-PCR). Five of 16 patients (31%)
      had dystrophin cDNA of abnormal size. One patient had a deletion, and two
      duplications that were not covered by multiplex PCR, one an exon-skipping of exon
      51 caused by a 5' consensus splice site mutation of intron 51, and one 172 bp or
      202 bp insertion in the cDNA between exon 25 and 26. Nested RT-PCR from the total
      RNA extracted from muscle biopsy was useful for screening patients who had no
      identifiable gene abnormality by multiplex PCR.

PMID- 9628193
TI  - Three siblings of fatal infantile encephalopathy with olivopontocerebellar
      hypoplasia and microcephaly.
AB  - We report three male siblings born with fatal encephalopathy comprising
      microcephaly, myoclonus and muscle hypertonia. All three patients died during
      infancy. Postmortem examination on the brain revealed that all infants had
      neuronal loss in the cerebellar cortex, inferior olivary and pontine nuclei,
      which were more pronounced in the older subject than the younger ones. In
      addition, they were associated with polymicrogyria in the cerebral cortex of the
      insula, olivary and dentate nuclear dysplasia, and a hypoplastic corticospinal
      tract. The clinical and neuropathological findings in our cases were identical to
      those in fatal infantile encephalopathy with olivopontocerebellar hypoplasia and
      microencephaly [Albrecht et al., Acta Neuropathol 1993;85:394-399], but an
      association of malformations suggests a new genetic factor in pathogenesis of
      olivopontocerebellar hypoplasia.

PMID- 9628194
TI  - Congenital ocular motor apraxia associated with myopathy, external hydrocephalus
      and NADH dehydrogenase deficiency.
AB  - Congenital ocular motor apraxia (COMA), first described by Cogan [Trans Am Acad
      Ophthalmol Otolaryngol 1952;56:853-862], is a rare disorder characterized by
      impairment of voluntary and optically induced horizontal eye movements and
      compensatory head thrust. The causes and pathogenesis of COMA are poorly
      understood. It frequently occurs in association with other neurologic
      abnormalities including non-progressive congenital disorders of the central
      nervous system (CNS), various systemic diseases and chromosomal alterations.
      Here, we report the case of a 6-month-old girl with psychomotor retardation,
      myopathy and clinical features of COMA, associated with external hydrocephalus
      and mitochondrial dysfunction (partial deficiency of the respiratory-chain enzyme
      NADH dehydrogenase). In view of this finding, we recommend that tests to
      characterize patients with COMA should include determination of blood levels of
      lactic and pyruvic acid.

PMID- 9628195
TI  - A case of parietal lobe epilepsy with distinctive clinical and neuroradiological
      features.
AB  - We present a case of parietal lobe epilepsy, the epileptogenic focus of which was
      conspicuously demonstrated on magnetoencephalography (MEG). The remarkable
      fluctuation in the seizure frequency and the presence of atonic seizures were
      suggestive of atypical partial benign epilepsy of childhood (APBEC). An
      interictal positron emission tomography (PET) scan performed during the cluster
      of fits revealed hypermetabolism around the epileptogenic focus, which might be
      related to the marked tendency of clustering of seizures in this patient.

PMID- 9628196
TI  - Three malformation complexes related to neural crest development.
AB  - We present an individual with three distinct malformation complexes, DiGeorge
      syndrome, CHARGE association and Dandy-Walker malformation. An extensive
      literature review has shown that DiGeorge syndrome and CHARGE association rarely
      occur simultaneously. The presence of both these malformation complexes with
      Dandy-Walker malformation has not been previously reported. These three
      malformation complexes may all be related by neural crest maldevelopment.

PMID- 9628197
TI  - Cyclic vomiting and elevation of creatine kinase associated with bitemporal
      hypoperfusion and EEG abnormalities: a migraine equivalent?
AB  - A 13-year-old mentally retarded boy suffered from repeated vomiting attacks since
      infancy. Each episode lasted 2 to 10 days, and was precipitated by respiratory
      infection, exercise or stress. During an attack he became irritated, agitated and
      amnesic, but did not have headaches or seizures. Associated findings were
      transient elevation of serum creatine kinase (CK) (331-3381 IU/l), and of plasma
      ACTH and cortisol. The raised CK level was the result of muscle hypertonicity.
      Ictal EEGs showed delta activity in the front-temporal areas, and inter-ictal IMP
      SPECT revealed hypoperfusion in both temporal regions. Unlike the periodic ACTH
      ADH discharge syndrome, neither hypertension nor depression developed. These
      attacks were diagnosed as a migraine equivalent and were suppressed with
      phenytoin. From the EEG and SPECT findings, we concluded that the vomiting and
      behavioural changes were related to the paroxysmal vascular abnormality in the
      temporal regions, but it was not easy to make the distinction between migraine
      and focal epilepsy. Before a diagnosis of the periodic ACTH-ADH discharge
      syndrome is made, the possibility of migraine equivalent should be considered.

PMID- 9628198
TI  - Isolated lissencephaly sequence with balanced chromosome translocation involving
      17p13.3.
AB  - We describe a patient with isolated lissencephaly sequence (ILS) who had a de
      novo balanced translocation with breakpoint at 8p11.23 and 17p13.3. She developed
      infantile spasms and had severe developmental delay. There was no apparent
      deletion of 17p13.3 on fluorescence in situ hybridization (FISH) analysis. The
      breakpoint was located centromeric to the Miller-Dieker syndrome (MDS) marker
      (D17S379), and telomeric to the marker D17S1566, which is located centromeric to
      the LIS1 gene. This is the second reported case of ILS with balanced
      translocation. It is suspected that the breakpoint of 17p13.3 in this patient is
      located in the responsible gene for ILS.

PMID- 9628199
TI  - Toward integrated healthcare: practical and philosophical issues at the heart of
      the integration of biomedical, complementary, and alternative medicines.

PMID- 9628200
TI  - Complementary healthcare policy.

PMID- 9628201
TI  - Chinese herb nephropathy is not a (dex)fenfluramine nephropathy but a serotonin
      nephropathy.

PMID- 9628202
TI  - Can physics and physical chemistry explain the workings of homeopathy? A
      clinician's view.

PMID- 9628203
TI  - An appraisal of the life and work of Dr. Josef Maria Issels 1907-1997.

PMID- 9628204
TI  - Emanuel Revici, M.D.: innovator in nontoxic cancer chemotherapy 1896-1997.

PMID- 9628205
TI  - The basic concepts of alternative medicine and their impact on our views of
      health.

PMID- 9628206
TI  - Methodological and ethical issues in clinical trials of acupuncture.
AB  - In this review, controlled clinical trials of acupuncture are placed into five
      categories on the basis of the treatment with which acupuncture is compared.
      Methodological and ethical issues relevant to each category are discussed. Wait
      list (or no treatment) controls, which are ethically acceptable for stable,
      chronic conditions, assess the efficacy of acupuncture relative to the natural
      history of the condition but do not control for nonspecific treatment effects.
      Placebo controls, defined here as noninvasive procedures such as inactive
      transcutaneous electrical nerve stimulation (TENS) or mock needling, assess
      whether acupuncture has an effect beyond that of the therapeutic milieu. Sham
      controls, defined as invasive but inappropriate procedures such as shallow
      needling at nonacupoint sites, assess whether acupuncture efficacy depends on the
      style and location of needling. Standard care comparisons assess whether
      acupuncture performs at least as well as a medication, medical device, or
      physiotherapy. Adjunctive care comparisons assess the efficacy of acupuncture
      plus standard care relative to standard care alone. From an ethical perspective,
      active debate surrounds placebo and sham controls. Those who argue against these
      procedures consider withholding treatment to be improper. They favor the wait
      list and both standard care designs in which all patients receive treatment.
      Others argue that testing a treatment prior to demonstrating its efficacy against
      a placebo is equally improper. From a methodological perspective, it should also
      be considered that most clinical trials of acupuncture have assessed its efficacy
      by administering a fixed course of treatment based on biomedical diagnosis. The
      challenge for future trials is to design conditions that more closely mimic the
      delivery of acupuncture in clinical practice, as individualized treatment
      informed by its own diagnostic traditions.

PMID- 9628207
TI  - Qigong Yangsheng as a complementary therapy in the management of asthma: a single
      case appraisal.
AB  - OBJECTIVES: Qigong Yangsheng, the health-promoting method of traditional Chinese
      medicine that combines movement, mental exercise, and breathing technique, is
      used in China for the therapy of bronchial asthma, and for some time now has been
      enjoying an ever-widening acceptance in the Western world as well. This pilot
      study investigates if Qigong Yangsheng could be used as a complementary
      therapeutic measure to treat asthma patients in a Western industrialized country.
      DESIGN: Thirty asthma patients, with varying degrees of illness severity, were
      taught Qigong Yangsheng under medical supervision. They were asked to exercise
      independently, if possible, on a daily basis and to keep a diary of their
      symptoms for half a year including peak-flow measurements three times daily, use
      of medication, frequency and length of exercise as well as five asthma-relevant
      symptoms (sleeping through the night, coughing, expectoration, dyspnea, and
      general well-being). The concept of this study was based on a single-case
      research design series with baseline, one teaching phase, a phase of self
      practice and a refresher teaching course. A 4-week follow-up period was carried
      out in the same season as the original baseline phase 52 weeks later. RESULTS: An
      improvement was indicated if subjects showed a decrease of at least 10 percent in
      peak-flow variability between the 1st and the 52nd week. This occurred more
      frequently in the group of the exercisers (n = 17) than in the group of
      nonexercisers (n = 13) (p < 0.01 chi-square with Yates correction). When
      comparing the study year with the year before the study, there was improvement
      also in reduced hospitalization rate, less sickness leave, reduced antibiotic use
      and fewer emergency consultations resulting in reduced treatment costs.
      CONCLUSION: Qigong Yangsheng is recommended for asthma patients with professional
      supervision. An improvement in airway capability and a decrease in illness
      severity can be achieved by regular self-conducted Qigong exercises.

PMID- 9628208
TI  - Health and disease in organizations.
AB  - This article introduces some concepts from complexity theory and examines
      organizations as living systems which experience both health and disease.
      Orthodox management practice is considered in this context, and the authors
      introduce their own approach called Conditioned Emergence as a form of
      alternative therapy for organizations. Parallels are identified between
      management research and research in a number of other disciplines and the paper
      concludes that complexity theory may offer a new scientific paradigm in which
      orthodox and alternative approaches may be reconciled.

PMID- 9628209
TI  - Chinese medicine users in the United States. Part II: Preferred aspects of care.
AB  - OBJECTIVES: While a limited amount of data describe who seeks Chinese medicine
      care and for what conditions, there have been few attempts to explain what users
      think the care does for them, or why they value and "like" the care. This article
      presents such data via an analysis of a sample of 460 handwritten stories
      collected as part of a mixed quantitative qualitative survey of 6 acupuncture
      clinics in 5 states. RESULTS: Quantitative data collected in this survey (Part I)
      showed that respondents were highly satisfied with their Chinese medicine care.
      The qualitative analysis found that respondents valued relief of presenting
      complaints as well as expanded effects of care including improvements in
      physiological and psychosocial adaptivity. In addition, respondents reported
      enjoying a close relationship with their Chinese medicine practitioner, learning
      new things, and feeling more able to guide their own lives and care for
      themselves. While these factors mesh well with Chinese medicine theory,
      respondents did not reveal familiarity with that theory. Instead, their language
      and experiences indicate familiarity with an holistic model of healthcare--and
      they seem to have experienced Chinese medicine care as holistic care.
      CONCLUSIONS: This finding matters because it shows that respondents are not
      seeking an 'exotic' kind of healthcare, but are utilizing a homegrown, if
      nonmainstream, model of healthcare. The finding also matters because it shows
      that an holistic health delivery model is not only feasible, but currently exists
      in the United States: how Chinese medicine practitioners are trained, and how
      they subsequently deliver their care, could serve as a model for American
      healthcare reform.

PMID- 9628210
TI  - On quantitative and qualitative research.

PMID- 9628211
TI  - Physical exercise in rehabilitation program for cancer patients?

PMID- 9628212
TI  - Integrated healthcare: a way forward for the next five years? A discussion
      document from the Prince of Wales's Initiative on Integrated Medicine.

PMID- 9628213
TI  - A critique of the limiting consequences of current thinking in healthcare and
      proposals for the next millenium: reflections on the catallactics for integrated
      healthcare delivery.

PMID- 9628214
TI  - One possible future.

PMID- 9628215
TI  - Simple one-tube reverse transcription-polymerase chain reaction protocol
      containing anticontamination procedure for detection of GB virus C/hepatitis G
      virus RNA.
AB  - A simple one-tube reverse transcription-polymerase chain reaction protocol for
      detection of GB virus C/hepatitis G virus (GBV-C/HGV) RNA in serum samples
      containing anticontamination uracil-N-glycosylase procedure was developed.
      Amplification products were detected in a standard microtiter plate format using
      a commercial PCR ELISA kit (Boehringer Mannheim, Germany). Complete agreement
      between the results of a novel method and the previously determined GBV-C/HGV RNA
      status was obtained on 131 serum samples (76 GBV-C/HGV RNA positive and 55 GBV
      C/HGV RNA negative samples). The novel method provides the potential for
      automated, simple, rapid and accurate routine detection of GBV-C/HGV RNA in
      diagnostic virological laboratories.

PMID- 9628216
TI  - An immunoassay with bovine serum albumin coupled peptides for the improved
      detection of anti V3 antibodies in HIV-1 positive human sera.
AB  - The V3 loop of the gp120 envelope glycoprotein contains the principal
      neutralizing determinant of HIV-1. Many serological studies have been carried out
      to assess the reactivity of HIV-1 infected individuals against V3 loop synthetic
      peptides from different HIV-1 subtypes. V3 directed serology has also been used
      to demonstrate the association between ELISA reactivity and progression to AIDS
      in HIV patients, and to study the reactivity against the V3 region in sera from
      vaccinated animals and human volunteers. The advantage of the use of bovine serum
      albumin (BSA) conjugated V3 peptides over free V3 peptides for ELISA is
      described. 15 meric V3 peptides representing several HIV-1 isolates were
      synthesized, chemically coupled to BSA, and used to coat ELISA microplates.
      Conjugated peptides were compared with free peptides for the detection of anti V3
      antibodies in the sera from rabbits immunized with V3 containing chimeric
      proteins and from HIV-1 infected individuals. No differences in reactivity
      against free or BSA-peptide were found for most rabbit sera, however human plasma
      recognized preferentially the BSA conjugated peptides. Although technically more
      complex, ELISA with BSA coupled V3 peptides is more sensitive and appropriate for
      serological studies of HIV-1 infected persons.

PMID- 9628217
TI  - Discrimination between different types of human adeno-associated viruses in
      clinical samples by PCR.
AB  - Persistent infection of human tissues with the helper virus-dependent parvovirus,
      adeno-associated virus (AAV) was detected by polymerase chain reaction (PCR)
      using primer pairs detecting AAV types 2, 3 or 5. In order to develop PCR
      protocols which discriminate between the different serotypes of AAV, the DNA of
      AAV-5 was sequenced partially and compared with the published sequences of AAV-2
      and -3. Type specific oligonucleotides and specific probes which allow the
      distinction between human AAV types by PCR are described.

PMID- 9628218
TI  - Characterization of rabbit hemorrhagic disease virus field isolates in Taiwan.
AB  - Liver tissues from animals that were suspected to have died of rabbit hemorrhagic
      disease (RHD) were used for isolation and characterization of the causative
      agent. Three strains of RHD virus were isolated as the supernatants of liver
      homogenates reacted positively by hemagglutination (HA) assays and were infective
      for rabbits after second passage in animals. Following extraction of liver
      homogenates from animals infected with each of three isolates, each virus strain
      was purified by CsCl density gradient ultracentrifugation for further
      characterization. In negative-stained preparations, the purified virions were
      icosahedral, measured approximately 40 nm in diameter, and were without an
      envelope. Morphologically, the three isolates were identical. By immunoblotting,
      a protein with a molecular weight of 60,000 was identified as the major
      structural protein in each isolate. Furthermore, two sets of primer framed two
      different regions within RHD virus genome and could amplify two fragments of the
      expected size, respectively, from each isolate, whereas, none were obtained from
      uninfected control samples. The identity of the amplified products was confirmed
      further using different restriction endonucleases. Among three isolates of RHD
      virus, neither protein migration patterns of the virions nor cleavage patterns of
      the amplified product by restriction enzymes were found to differ.

PMID- 9628219
TI  - Measles virus fusion protein- and hemagglutinin-transfected cell lines are a
      sensitive tool for the detection of specific antibodies by a FACS-measured
      immunofluorescence assay.
AB  - A FACS-measured immunofluorescence assay was developed for the detection of
      antibodies directed against the hemagglutinin (H) and fusion (F) glycoproteins of
      measles virus (MV). Human melanoma cell lines transfected with either the MV H or
      F genes, which showed a high surface expression of the respective proteins in
      their native conformation, were used as target cells. The cells were incubated
      with diluted plasma samples, and stained subsequently with FITC-conjugated
      secondary antibodies. The FACS-measured fluorescence signals correlated directly
      with the amount of specific immunoglobulins over a wide concentration range. The
      use of different conjugates enabled the separate detection of MV-specific IgG,
      IgM, IgA and IgG subclasses, with relatively low backgrounds. Hemagglutinin
      specific IgG, IgM and IgA fluorescence signals were shown to correlate well with
      MV-specific IgG ELISA titers and MV-specific IgM or IgA capture ELISA OD450
      values, respectively. The polyclonal conjugates with specificity for human
      immunoglobulins offered sufficient cross-reactivity to detect MV-specific IgG,
      IgM and IgA in plasma samples of cynomolgus macaques, making this technique a
      useful tool for studying serological responses in vaccination and challenge
      experiments in non-human primate models.

PMID- 9628220
TI  - A small-scale procedure for extracting nucleic acids from woody plants infected
      with various phytopathogens for PCR assay.
AB  - The complexity of most nucleic acid extraction procedures limits the number of
      samples that can be easily processed for analysis by polymerase chain reaction
      (PCR). A simple, small-scale procedure was developed which can be carried out
      entirely in 1.5-ml microfuge tubes whereby the container and contents are frozen
      with liquid nitrogen, tissue is pulverized, and targeted nucleic acids are
      extracted. DNA of bacterial and phytoplasmal plant pathogens was extracted in hot
      CTAB buffer followed by chloroform clarification. Following centrifugation, the
      DNA in the aqueous fraction was precipitated with isopropanol and resuspended in
      water. RNA originating from viruses and viroids was extracted from triturated
      tissue using STE buffer and phenol. The nucleic acid fraction was purified using
      CF-11 cellulose. All purified preparations were used as PCR or RT-PCR templates
      to detect DNA or RNA, respectively. These procedures were used to detect Xylella
      fastidiosa, peach yellow leaf roll phytoplasma, sour cherry green ring mottle
      virus, and peach latent mosaic viroid by agarose gel electrophoresis.

PMID- 9628221
TI  - A simple and sensitive method for detecting adenovirus in serum and urine.
AB  - A method to detect shed virus in patients' serum and urine was developed
      following Ad5CMV-p53 gene transfer via direct tumor injections. The procedure
      differs from those reported previously in that it first uses polyethylene glycol
      to precipitate adenoviral particles from patient serum or urine. Adenoviral DNA
      is then extracted following proteinase K digestion. Finally, polymerase chain
      reaction (PCR) amplification followed by Southern blot transfer are employed to
      enhance the limit of detection to less than ten viral particles. The detection
      limit in a 0.25-ml sample is five viral particles in serum and one viral particle
      in urine. This procedure is sensitive, reproducible, and can be completed in less
      than 2 days.

PMID- 9628222
TI  - Separation of Slovenian isolates of PVY(NTN) from the North American isolates of
      PVY(N) by a 3-primer PCR.
AB  - The potato tuber ringspot necrosis isolate of potato virus Y (PVY(NTN)) is a
      recently recognized and highly aggressive isolate of the PVY(N) group of strains.
      In order to screen specifically sources of resistance to PVY(NTN) a method to
      separate PVY(NTN) from PVY(N) is needed. To achieve this, 61 isolates from 13
      imported and locally developed potato cultivars in Slovenia were studied. On the
      basis of the reactions in indicator plants Nicotiana tabacum cv. Samsun and
      Solanum brachycarpum and with a PVY(N) specific monoclonal antibody (4E7), all
      Slovenian isolates (Sl-NTN) were identified as PVY(N). Using two primer pairs
      from the P1 gene of a Hungarian isolate of PVY(NTN) by a conventional single
      primer pair, reverse transcription polymerase chain reaction (RT-PCR) both
      PVY(NTN) and PVY(N) were amplified similarly. However, specific amplification of
      PVY(NTN) was achieved by a nested-PCR at an annealing temperature of 63 degrees
      C. A simplified form of the nested-PCR, termed 3-primer PCR was developed, which
      is applicable for large-scale testing of samples. Using the 3-primer PCR at
      annealing temperature of 63 degrees C, known mixtures of PVY(NTN) and PVY(N) were
      correctly separated. PVY(NTN) was detected in dormant tubers and leaves from all
      Sl-NTN isolates. The 3-primer PCR was specific to PVY(NTN) and did not react with
      nine isolates of PVY(N), 13 isolates of PVY(o), one isolate of PVY(C), six
      commonly occurring potato viruses and a viroid.

PMID- 9628223
TI  - A novel nested reverse transcription PCR detects bovine viral diarrhoea virus in
      fluids from aborted bovine fetuses.
AB  - A nested reverse transcription-PCR (RT-PCR) was developed to detect pestivirus
      nucleic acid in fetal fluids and to study the number of bovine abortions
      associated with BVDV infection. Three techniques for the extraction of viral RNA
      from fetal fluids were compared; phenol:chloroform method, treatment with
      Catrimox-14 followed by guanidium isothiocyanate buffer and the Qiagen total RNA
      kit. The Qiagen kit was the most sensitive and reproducible and therefore
      adopted. After cDNA synthesis, initial amplification of a 288-base pair product
      using existing primers derived from the highly conserved 5'-untranslated region
      of the BVDV genome was achieved. Newly designed internal primers yielded a 171
      base pair fragment which was visualised after electrophoresis on an ethidium
      bromide-stained gel. This assay detected 6.0 TCID50 of BVDV per 300 microl of
      artificially contaminated fetal fluid. One hundred fetal fluids were screened for
      the presence of BVDV RNA and the results compared with existing virus isolation
      methods. The BVDV antibody status of each fetus was determined. The nested RT-PCR
      detected BVDV RNA in eight of the hundred fetal fluids screened, whereas BVD
      virus was isolated from only one sample. The use of the nested RT-PCR will
      provide us with a more accurate picture of bovine embryonic infection due to
      BVDV.

PMID- 9628224
TI  - A rapid and sensitive bacterial assay to determine the inhibitory effect of
      'interface' peptides on HIV-1 protease co-expressed in Escherichia coli.
AB  - The HIV-1 protease is essential for maturation of virus particles and is,
      therefore, an attractive target for antiviral drugs. The function of this
      protease depends on the dimerization of two identical subunits. Commonly used
      protease inhibitors are directed mainly against the active site of the enzyme
      which often leads to viral resistance. To determine the inhibitory effect of
      peptides interfering with the dimerization site of the HIV-1 protease, a
      recombinant bacterial screening assay was established. Escherichia coli was co
      transformed with two different plasmids, expressing the 'interface' peptide and
      an active HIV-1 protease toxic for the bacteria. Co-expression of inhibitory
      peptides overcomes the incomplete membrane transmission of supplemented
      inhibitors and leads to a direct interaction of the inhibitory peptide and the
      HIV-1 protease. The inhibitory effect of co-expressed peptides was measured by an
      increased growth of co-transformed bacteria, compared with a slowly growing E.
      coli control culture only expressing the HIV-1 protease. Using this assay several
      penta- and hexa-peptides were screened for their ability to inhibit HIV-1
      protease activity. One of these peptides showed a significant inhibitory effect
      on co-expressed recombinant HIV-1 protease.

PMID- 9628225
TI  - Equine monocyte-derived macrophage cultures and their applications for
      infectivity and neutralization studies of equine infectious anemia virus.
AB  - Equine infectious anemia virus (EIAV) has been shown to infect cells of
      monocyte/macrophage lineage. These primary cells are intrinsically difficult to
      obtain, to purify and to culture in vitro for extended periods of time. As a
      result, most in vitro studies concerning this lentivirus make use of primary
      equine fibroblasts or transformed canine or feline cell lines. We describe
      methods that yield reproducibly pure cultures of equine blood monocytes from
      peripheral blood mononuclear cells. The in vitro differentiation of these cells
      into mature equine macrophage was verified using various cytochemical staining
      methods. The equine monocyte-derived macrophage (MDM) cultures were found to
      replicate cell-adapted and field strains of EIAV more efficiently than cultures
      of fully differentiated equine splenic macrophage. Having established
      reproducible and fully differentiated cultures of equine macrophage, in vitro
      assays of virus infectivity and serum neutralization were developed using the in
      vivo target cell of EIAV. These procedures, while developed for the EIAV system,
      should be equally useful for in vitro cultures of other macrophage-tropic
      pathogens of horses.

PMID- 9628226
TI  - A nested-PCR assay for the simultaneous amplification of HSV-1, HSV-2, and HCMV
      genomes in patients with presumed herpetic CNS infections.
AB  - To facilitate early diagnosis of herpes virus infection of the central nervous
      system (CNS), a nested polymerase chain reaction (nPCR) assay was developed to
      test simultaneously for the presence of HSV-1, HSV-2, and HCMV DNA in the
      cerebrospinal fluid (CSF) of patients with herpetic CNS disease suspected on
      clinical grounds. The virus type-specific PCR products were differentiated either
      by agarose gel electrophoresis or by DNA enzyme immunoassay. Using titrated viral
      stocks as standards, a sensitivity of at least 0.03 infectious units was obtained
      for HSV-1, HSV-2 and HCMV and no cross-reactions were recorded. Among 178 CSF
      specimens (171 patients), which were tested under routine conditions, three
      contained HSV-1 DNA, one contained HSV-2 DNA and one contained HCMV DNA. No
      double or triple infection was diagnosed. The presence of inhibitors of the Taq
      DNA polymerase was monitored by spiking aliquots of the above CSF samples with 3
      infectious units each of HSV-1 and HSV-2 or HCMV. Whereas none of 93 samples
      spiked with HSV-1 and HSV-2 contained inhibitors, the PCR reaction was inhibited
      in three out of 175 samples (1.7%) spiked with HCMV. The complete procedure which
      requires only 150 microl of CSF is easily completed within 8 h. Through its
      speed, reliability and sensitivity, this nPCR assay has met the specific criteria
      of the diagnostic laboratory.

PMID- 9628227
TI  - The in vivo production of Spodoptera littoralis nuclear polyhedrosis virus.
AB  - The in vivo production of the nucleopolyhedrovirus (NPV) of the Egyptian cotton
      leafworm Spodoptera littoralis was studied experimentally. Larvae (7 days old) of
      30-50 mg were experimentally infected with a range of NPV doses then harvested
      alive at various times after dosing to determine the effect of dose and
      incubation time on NPV productivity. Maximum NPV production achieved after 7 days
      incubation was 1.86 x 10(9) polyhedral inclusion bodies (PIBs) per larvae using
      an inoculum of 1 x 10(4) PIBs. Adjusting the inoculum dose had limited impact on
      NPV productivity but the correct selection of harvesting time was crucial in
      maximising the yield, both to achieve peak NPV production in individual larvae
      and to avoid losses from the death and disintegration of larvae if harvesting was
      delayed too long.

PMID- 9628228
TI  - Combination of whole blood culture and a rapid and sensitive cell assay for the
      determination of the cytopathogenicity of human immunodeficiency virus type-1
      isolates.
AB  - It has been reported that in vitro biological properties of human
      immunodeficiency virus type 1 (HIV-1) isolates from patients are correlated with
      the prognosis of HIV-1 infection. A rapid assay was developed to study the
      phenotype of HIV-1 isolates. The P4 cell line is a HIV-1 infectible Hela CD4 cell
      carrying the bacterial LacZ gene under the control of the HIV-1 LTR (long
      terminal repeat). Conventional peripheral blood mononuclear cells (PBMCs) co
      culture and heparinized whole blood (HWB) co-culture with normal PBMCs were used
      for HIV-1 isolated strains from 17 HIV-1-infected patients. The sensitivity of P4
      cells was higher than that of MT-2 cells for detecting syncytia induced by HIV
      1LAI (lymphadenopathy-associated virus). Like MT-2 cells, P4 cells enable the
      detection of syncytium inducing strains isolated in peripheral blood mononuclear
      cells (PBMCs) and HWB cultures. HIV-1 isolates with both culture methods from
      certain patients induced cytolysis without syncytium in P4 cells but had no
      cytopathic effect on MT-2 cells. The experiments are in favour of the direct
      effect of HIV-1 isolates of these patients in the lysis of P4 cells but its
      mechanism has not been elucidated. It was shown that the combination of whole
      blood culture for HIV-1 isolation and phenotype study with P4 cell assay is rapid
      and sensitive and could be used to monitor HIV-1-infected patients.

PMID- 9628229
TI  - Ventilatory response to asphyxia in conscious rats: effect of ambient and body
      temperatures.
AB  - In many mammals the ventilatory response to hypoxia depends on ambient
      temperature (Ta), largely because of the hypometabolic effects of hypoxia below
      thermoneutrality. We questioned whether the ventilatory response to asphyxia also
      depends upon Ta, and the role played by metabolism and body temperature (Tb).
      Oxygen consumption (VO2) and pulmonary ventilation (VE) were measured in
      conscious rats at Ta = 27 degrees C (warm) and 11 degrees C (cold), breathing air
      or two levels of asphyxic gases, moderate (10% O2-4% CO2), or severe (10% O2-8%
      CO2), for approximately 30 min each. In the cold, the pattern of the VE response
      to moderate asphyxia was qualitatively similar to that seen in hypoxia alone, i.e
      the attained VE/VO2 was similar in warm and cold conditions, with, in the latter,
      a major drop in VO2 and little or no hyperpnea. During severe asphyxia, however,
      the VE/VO2 attained in the cold was less than in the warm, and it was accompanied
      by a large drop in Tb (approximately 6 degrees C). Blood gases confirmed the
      lower asphyxic hyperventilation in the cold. By maintaining Tb at 38 degrees C
      with an implanted abdominal heat exchanger, the VE/VO2 levels attained during
      asphyxia were the same between cold and warm conditions. We conclude that (a) the
      VE response to asphyxia is Ta-dependent, largely because of the hypometabolic
      effect of the hypoxic component in the cold, (b) during moderate asphyxia the
      hypercapnic component is qualitatively unimportant, and (c) with severe asphyxia
      the hypercapnia becomes an important contributor to the Ta-sensitivity by
      aggravating the decrease in Tb in the cold and lowering VE sensitivity.

PMID- 9628230
TI  - Ventilatory and metabolic responses to cold and hypoxia in conscious rats with
      discrete hypothalamic lesions.
AB  - We tested the hypothesis that hypothalamic nuclei involved in thermoregulatory
      control could represent a site of integration of the metabolic and ventilatory
      response to cold and hypoxia. Electrolytic lesions were performed bilaterally
      under stereotaxic guide, either within the anterior or posterior hypothalamic
      areas of adult rats. One week later, oxygen consumption (VO2) and ventilation
      (VE) were measured in the conscious animals during warm (27 degrees C) or cold
      (12 degrees C) conditions, in normoxia (21% O2) or hypoxia (10% O2), and compared
      to measurements obtained in control rats, which were either intact or sham
      operated. VO2, VE, and body temperature did not differ between lesioned and
      control rats during warm normoxia. In cold and hypoxia, singly or combined,
      VE/VO2 was higher in the lesioned rats, because of higher VE. The differences in
      the cold were mostly confined to rats with anterior lesions, whereas differences
      in hypoxia were mostly in rats with posterior lesions. We conclude that the
      integrity of the anterior and posterior hypothalamic areas is important for the
      proper coupling of metabolism and ventilation during cold or hypoxic stimuli.

PMID- 9628231
TI  - Role of hypoxemia and hypercapnia in acute cardiovascular response to periodic
      apneas in sedated pigs.
AB  - The effects of hypoxemia and hypercapnia in acute cardiovascular response to
      periodic non-obstructive apneas were explored in seven preinstrumented, sedated
      paralyzed and ventilated pigs under three conditions: room air breathing (RA), O2
      supplementation (O2), and supplementation with O2 and CO2 (CO2). EEG monitoring
      showed no arousal under any conditions. RA apneas increased mean arterial
      pressure (MAP, from baseline 95.9 +/- 4.5 to late apnea 124.4 +/- 7.8 Torr, P <
      0.01), left ventricular end-diastolic pressure, end-diastolic and end-systolic
      myocardial fiber lengths and systemic vascular resistance, but decreased cardiac
      output (CO, 3.09 +/- 0.34-2.37 +/- 0.26 L/min, P < 0.01), heart rate (HR, 115.1
      +/- 7.5-102.0 +/- 7.8 bpm, P < 0.01), and stroke volume (SV, 29.6 +/- 0.7 21.1 +/
      1.8 ml, P < 0.01). 02 apneas produced similar decreases in HR (114.0 +/- 11.8
      105.4 +/- 8.7 bpm, P < 0.05) as with RA apneas, but smaller increases in MAP
      (94.5 +/- 1.8-103.4 +/- 2.8 Torr, P < 0.01) and in the variables of pre- and
      after-load. CO and SV remained unchanged with O2 apneas. CO2 was associated with
      higher MAP, CO, and HR at baseline relative to RA, but similar cardiovascular
      response during apneas in direction and magnitude to those of O2 apneas. We
      conclude that in this model hypoxemia is a major but not the sole determinant of
      the pressor response during apneas. Hypercapnia cannot explain the pressor
      response seen when hypoxemia is abolished. The HR fall during apneas is
      independent of hypoxemia, hypercapnia and the pressor response.

PMID- 9628232
TI  - The time course of pulmonary diffusing capacity for carbon monoxide following
      short duration high intensity exercise.
AB  - We investigated the time course of changes in post-exercise pulmonary diffusing
      capacity for carbon monoxide (DLCO), membrane diffusing capacity (DM), and
      pulmonary capillary blood volume (VC) in highly trained (HT), moderately trained
      (MT) and untrained (UT) male subjects (n = 8/group). Subjects were assigned to
      groups based on their aerobic capacity from a preliminary VO2max test (HT > or =
      65, MT = 50-60, UT < or = 50 ml x kg(-1) x min(-1)). Resting (BASE) DLCO, DM and
      VC were obtained, then subjects cycled to fatigue at the highest workrate
      attained during the preliminary tests. Diffusion measurements were then made at
      1, 2, 4, 6 and 24 h. DLCO was depressed at 1 h, lowest at 6 h and approached BASE
      values at 24 h in all groups. The DLCO change was paralleled by a change in VC.
      Alterations to VC were similar between groups except at 24 h where MT and HT
      subjects had returned to BASE while UT did not. DM was significantly lower than
      BASE at 1, 2, 4, and 6 h, and was similar between groups. The changes in DLCO
      post-exercise appear to be primarily due to a decrease in VC. Comparable
      diffusion decrements were observed in all subjects. The results of this study
      suggest that post-exercise alterations in DLCO, DM and VC are not related to
      aerobic capacity.

PMID- 9628233
TI  - Role of carotid body in pressure response of pulmonary circulation in rats.
AB  - We investigated how signals arising from peripheral chemoreceptors could affect
      pulmonary vasculature in rats. Effects of the hypoxic exposure (10%) on mean
      pulmonary arterial pressure (mPAP), abdominal aortic flow (Q) and the estimated
      total pulmonary vascular resistance (mPAP/Q) were determined in anesthetized,
      artificially ventilated, carotid sinus nerve intact or chemodenervated rats. The
      pressor response of PAP to hypoxia seen in intact rats changed to the depressor
      response after chemodenervation. Hypoxia elicited a decrease in Q and an increase
      in mPAP/Q in both intact and chemodenervated rats. Selective carotid body
      stimulation by the intra-carotid injection of sodium cyanide (NaCN) in normoxia
      elicited an immediate but transient increase in PAP and Q before and after
      bilateral vagotomy. The peak change in PAP slightly preceded that in Q. These
      responses to NaCN were completely abolished by chemodenervation. These results
      indicate that the immediate chemoreflex contributes to the short-term regulation
      of pulmonary vasculature in rats.

PMID- 9628234
TI  - Effects of breathing pathways on tracheal sound spectral features.
AB  - The spectra of sounds recorded over the trachea of adults typically reveal peaks
      near 700 and 1500 Hz. We assessed the anatomical determinants of these peaks and
      the conditions contributing to their presence. We studied five adult subjects
      with normal lung function, measuring sounds at the suprasternal notch and on the
      right cheek. The subjects breathed at target airflows of 15 and at 30 ml sec(-1)
      kg(-1) both through the mouth with nose clips and then through the mouth and nose
      using a cushioned face mask. The mouth breathing maneuvers were performed with
      three lengths (3.6, 21.1 and 38.6 cm) of 2.6 cm diameter tubing between the mouth
      and the pneumotachograph. The nose breathing maneuver was performed with the
      longest tube (between the mask and pneumotachograph). The signals occurring at
      the target flows +/- 20% were used to create averaged, spectral estimates. We
      found that all subjects had two predominant spectral peaks; a approximately 700
      Hz peak loudest over the cheek and a approximately 1500 Hz peak loudest over the
      trachea. The frequency of both peaks negatively correlated with body height (and
      presumably, airway length). There was no systematic effect of breathing phase,
      flow rate or length of the tube connecting the mouth to the pneumotachograph on
      the spectral peaks. Breathing into the mask and breathing through the nose did
      markedly alter the spectra. We conclude that the higher tracheal sound peak
      reflects resonance within the major airways and is relatively independent of
      extrathoracic influences during mouth breathing through a tube.

PMID- 9628235
TI  - Inflammatory cytokines in BAL fluid and pulmonary hemodynamics in high-altitude
      pulmonary edema.
AB  - To evaluate the pathogenesis of high-altitude pulmonary edema (HAPE), we
      performed bronchoalveolar lavage (BAL) and pulmonary hemodynamic studies in seven
      patients with HAPE at its early stage. We measured cell counts, biochemical
      contents, and concentrations of pro-inflammatory cytokines including interleukin
      (IL)-1, IL-6, IL-8 and tumor necrosis factor (TNF)-alpha and of anti-inflammatory
      cytokines including IL-1 receptor antagonist (ra) and IL-10 in the BAL fluid
      (BALF). All patients showed increased counts for total cells, alveolar
      macrophages, neutrophils and lymphocytes, and markedly elevated concentrations of
      proteins, lactate dehydrogenase, IL-1beta, IL-6, IL-8, TNF-alpha and IL-1ra. The
      levels of IL-1alpha and IL-10 were not increased. Patients also showed pulmonary
      hypertension with normal wedge pressure. Both the driving pressure obtained as
      pulmonary arterial pressure minus wedge pressure and the PaO2 under room air were
      significantly correlated with the concentrations of IL-6 and TNF-alpha in the
      BALF. These findings suggest that the inflammatory cytokines play a role at the
      early stage of HAPE and might be related to pulmonary hypertension.

PMID- 9628236
TI  - The ontogeny of cardio-respiratory function under chronically altered gas
      compositions in Xenopus laevis.
AB  - The importance of diffusion and perfusion in terms of oxygen transport was
      evaluated by chronically altering environmental O2 availability (hypoxia or
      hyperoxia) and blood O2 content (carbon monoxide) through development in Xenopus
      laevis. Oxygen consumption (MO2), individual wet mass, heart rate (fH), and
      stroke volume (SV) were measured in animals raised from eggs to pre-metamorphic
      climax while maintained at 11, 21 and 35 kPa O2, combined with and without 2 kPa
      carbon monoxide. Additionally, cardiac output (Q), and a recently defined O2
      consumption/transport quotient (MO2 x QO2(-1)) were calculated. Wet mass, MO2,
      and fH, were not significantly different between controls and experimental
      treatments at any developmental stage. However, with hemoglobin oxygen transport
      blocked by carbon monoxide, the exposed larvae showed an increased SV, Q and MO2
      x QO2(-1). Combined, these data suggest that in spite of impaired blood O2
      convection, normal aerobic metabolism was maintained, indicating that direct
      diffusion of O2 plays an important role in supplying oxygen during early
      development.

PMID- 9628237
TI  - The protective effects of metabolic rate depression in hypoxic cold submerged
      frogs.
AB  - Aerobic metabolic rates (MO2) and respiratory quotients (RQ = MCO2/MO2) were
      measured in hypoxic frogs, hibernating underwater for up to 90 days at 3 degrees
      C. After 3 months of submergence at a PO2 of 50 mmHg, MO2 levels were 25% of
      those seen prior to hibernation. In progressive hypoxia, a gradual shift in RQ
      from 0.85 to 1.0 signaled an increasing reliance upon carbohydrate metabolism.
      Moreover, the glycogen concentrations of skeletal muscle, liver and heart of
      hypoxic frogs were more rapidly depleted than in their normoxic counterparts. A
      plasma lactacidosis revealed that the hypoxic animals recruited anaerobiosis to
      fuel a large 'Pasteur effect'. Throughout all stages of hypoxia, cellular ATP
      levels were maintained homeostatic. The ability to depress metabolic rate such
      that ATP demands can be met by oxidative phosphorylation in an oxygen limited
      environment is the key to the frogs' overwintering survival.

PMID- 9628238
TI  - The role of amylin in the physiology of glycemic control.
AB  - Amylin is a 37-amino acid peptide hormone, discovered in 1987, which is co
      located and co-secreted with insulin by the pancreatic beta-cells in response to
      nutrient stimuli. Like insulin, there is a deficiency of amylin in people with
      type 1 diabetes, while the changes in plasma amylin concentrations in people with
      impaired glucose tolerance and type 2 diabetes parallel those of insulin. It is
      well established that insulin regulates glycemic control by promoting glucose
      disposal. This paper reviews evidence from studies in animals and people with
      diabetes that amylin regulates the inflow of glucose to the circulation by
      delaying nutrient delivery and, thus, the appearance of meal-derived glucose, and
      also suppresses glucagon secretion in the postprandial period. It is suggested,
      therefore, that the actions of amylin complement those of insulin, and that the
      problems of glycemic control which continue to exist in people with diabetes,
      despite insulin replacement therapy, may be attributable to a deficiency in
      amylin. Preclinical and clinical studies with pramlintide, a synthetic analogue
      of human amylin, are also included in this brief review.

PMID- 9628239
TI  - Overnight GLP-1 normalizes fasting but not daytime plasma glucose levels in NIDDM
      patients.
AB  - GLP-1 (7-36 amide) normalizes fasting plasma glucose in NIDDM patients. It was
      the aim to study the effect of overnight intravenous GLP-1 (7-36 amide) on the
      following 24 h-glucose profiles. Ten NIDDM patients (7 female, 3 male; age 62 +/-
      4 y., BMI (Body-Mass-Index) 29.6 +/- 3.9 kg/m2, duration 10 +/- 7 y., HbA1c 10.9
      +/- 1.3% (normal 4.0-6.1%), treated with glibenclamide and/or metformin) were
      studied on two occasions in random order: Either GLP-1 (7-36 amide) (Saxon
      Biochemicals, Hannover, FRG, 1 pmol x kg(-1) x min(-1)) or placebo (0.9% NaCl
      with 1% human serum albumin, Behringwerke, Marburg, FRG) were infused
      intravenously from 22:00 to 7:00 (9 h) and plasma glucose profiles were obtained
      during the GLP-1 infusion and the following 24 hours. GLP-1 (7-36 amide) (plasma
      concentration 110 +/- 12 pmol/l) raised plasma C-peptide concentrations (p =
      0.0005), suppressed glucagon (p = 0.01) and lowered plasma glucose to 5.5 +/- 0.6
      and 6.3 +/- 0.4 mmol/l at 3:00 and 7:00 a.m. (vs. 10.3 +/- 0.9 and 11.3 +/- 0.6
      mmol/l, p = 0.0003 and p < 0.0001, respectively, with placebo). Thereafter,
      starting 1 h after breakfast, no significant differences in plasma glucose,
      insulin, C-peptide or glucagon profiles were found between experiments with GLP-1
      (7-36 amide) and placebo. Average plasma glucose concentrations over the whole 24
      h period were reduced by 18% by GLP-1 administered overnight. In conclusion, (1)
      overnight GLP-1 (7-36 amide) normalizes fasting plasma glucose, but (2) has no
      sustained effect on meal-induced glucose, insulin or glucagon concentrations once
      its administration has been stopped. (3) Normalization of fasting plasma glucose
      alone does not improve daytime metabolic control in NIDDM patients on oral
      agents.

PMID- 9628241
TI  - Prevalence of diabetes-specific autoantibodies in patients at risk for adult
      onset diabetes mellitus.
AB  - To evaluate the potential of autoimmune markers in identifying patients with
      slowly progressive IDDM in the prediabetic state, we screened a population of 151
      patients aged 37-70 years with impaired glucose tolerance (IGT) for the presence
      of islet cell antibodies (ICA), insulin autoantibodies (IAA), antibodies to
      glutamic acid decarboxylase (GADA), and antibodies to tyrosine phosphatase IA-2
      (IA-2A). Autoantibodies were found in 5 (3.3%) patients with IGT suggesting the
      presence of an autoimmune-mediated beta cell destruction. All of them were
      positive for high level ICA (> 20 JDF-U) and 1 ICA positive subject had
      additional GADA (100 GADA-U). In contrast, none of the subjects had IA-2A or IAA.
      We here demonstrate a low prevalence of autoimmune diabetes among middle-aged
      subjects with IGT. ICA and GADA but not IA-2A or IAA may represent autoimmune
      markers for slowly progressive IDDM before the manifestation of the disease.

PMID- 9628240
TI  - Screening for variability in the ciliary neurotrophic factor (CNTF) gene: no
      evidence for association with human obesity.
AB  - Systemic administration of the neurocytokine ciliary neurotrophic factor (CNTF)
      normalizes the obese phenotype of ob/ob and db/db mice. CNTF exerts its multiple
      effects through a receptor complex whose sequence, localization in hypothalamic
      nuclei and mode of signal transduction share remarkable similarities with the
      leptin receptor. In the human CNTF gene, a mutation in the first intron creates a
      new splice acceptor site, with the resulting mRNA coding for an aberrant protein
      (Takahashi et al., 1994). Given the potential of CNTF to influence energy
      homeostasis, this study was undertaken to determine whether variability in the
      CNTF gene is associated with human obesity. The previously described mutation was
      found in 30.3% of obese children and adolescents, 7 of which were homozygous
      (allele frequency 0.163). 29.5% of lean subjects carried the mutation, none of
      which were homozygous (allele frequency 0.148; corrected p = 1 compared to
      obese). No further mutations were detected by single strand conformational
      polymorphism (SSCP) analysis. In conclusion, variants in the CNTF gene are
      unlikely to be associated with the development of early-onset obesity.

PMID- 9628242
TI  - The influences of insulin and food intake on intestinal ornithine
      transcarbamylase activity in diabetic rats.
AB  - Intestinal ornithine transcarbamylase (OTC) activity was studied in rats with
      experimentally-induced diabetes. After the injection of streptozotocin, OTC
      activity was approximately 75% that of age-matched controls. Then we investigated
      the influences of (a) insulin treatment and (b) limiting food-intake, which was
      adjusted to the control level, on OTC activities in the three segments of the
      small intestine. (a) Insulin treatment resulted in OTC activities being restored
      to control levels in all segments of the small intestine, with the disappearance
      of intestinal epithelial hyperplasia. (b) In limited food-intake rats, OTC
      activities of the middle and distal segments normalized with insulin treatment.
      In the proximal segment, however, which showed epithelial hyperplasia, OTC
      activity was as low as that in untreated STZ rats. These observations suggest
      that altered regulation of intestinal epithelial over-growth and immoderate food
      intake were normalized by insulin treatment, leading to the restoration of normal
      OTC activity in the small intestine.

PMID- 9628243
TI  - Endosonography of the adrenal glands: normal size--pathological findings.
AB  - Transabdominal sonography of the adrenal glands frequently is non-successful. It
      was the aim of this project to improve the imaging of the adrenal glands using
      high resolution sonography in order to obtain information about even small
      changes in these organs. Therefore, endosonographic imaging was investigated
      using an endosonoscope PENTAX FG32UA. The correct identification of the adrenal
      glands was examined in five human cadavers. A total of 58 patients with 113
      adrenal glands (in 3 cases history of unilateral adrenalectomy) were
      investigated. 109 adrenal glands (97%) were identified and evaluated. Healthy
      adrenal glands are slightly hyperechoich and regarding their echogeneity
      comparable to other endocrine organs such as the testes or the thyroid. Adrenal
      size can be determined as largest cross sectional area and was found to be 216 +/
      93 mm2 right and 231 +/- 98 mm2 left. In the adrenal glands which could be
      imaged by endosonography, all findings detected by CT (n = 33) or MRI (n = 19)
      could also be demonstrated endosonographically. Additional information as
      compared to CT/MRI was obtained in 7 out of 33 and in 6 out of 19 patients. This
      concerns in particular differentiation between tumor and hyperplasia and
      detection of small adrenal adenomas. High resolution endosonography of the
      adrenal glands can provide information about adrenal gland morphology which
      cannot be obtained by any other diagnostic approach.

PMID- 9628244
TI  - Insulin-like growth factor binding protein-3 levels during early and late follow
      up after surgery in acromegalic patients.
AB  - Disease activity in acromegaly is accurately reflected by growth hormone (GH)
      concentration during oral glucose tolerance test (OGTT) and insulin-like growth
      factor-I (IGF-I) levels, representing an integrated index of GH activity. This
      prospective study was performed to evaluate whether plasma IGF binding protein 3
      (IGFBP-3) might also reflect the hormonal disease activity in pituitary
      acromegaly after operative treatment during early and late follow-up. Twenty-two
      acromegalic patients were studied. Data were obtained pre-, intra- and post
      operatively in 13 cases. In 9 patients the acromegalic activity was studied only
      after treatment. The hormonal assessment included repeated blood samples for
      estimation of IGF-I, IGFBP-3 and repeated OGTTs. In each case 100 sigma g
      octreotide (Sandostatin lambda, Sandoz, Basel) was injected to test the acute
      response of GH, IGF-I and IGFBP-3. Intraoperatively, GH levels were estimated to
      examine acutely the influence of tumour reduction on GH levels. Patients were
      considered cured when GH levels (GH60min) were less than 2 ng/ml during OGTT 4
      weeks after surgery. The data outlined that in patients with normalized GH60min
      levels, normalized IGFBP-3 levels were noticed 4 weeks and 12 months post
      operatively. In non-cured patients normalized IGFBP-3 concentrations were found
      in 11 out of 15 cases in the late post-treatment phase. In contrast only 1 of 7
      cured patients had persistently elevated IGF-I levels within the first month post
      operatively, whereas no case of the non-cured patients had IGF-I values in the
      normal range. Despite these observations a strong correlation of IGF-I and IGFBP
      3 did not exist before one year post-operatively -- either in the cured or in the
      non-cured patients. Serum IGFBP-3 in patients with pituitary acromegaly does not
      provide a predictive value of appreciable magnitude concerning cure or non-cure
      from the disease- whether examined early or late in the post-operative period.
      Absolute levels of IGFBP-3 may thus cause misinterpretation concerning cure of
      acromegalics after surgery.

PMID- 9628245
TI  - Final height and weight of long-term survivors of childhood malignancies.
AB  - The aim of this study was to investigate growth and final height in young adults
      after therapy for malignant diseases. Final height and weight was studied in 50
      long-term survivors (LTS) of childhood cancer (aged 17-31 years; 30 men, 20
      women) 3-18 years after treatment for malignant diseases (7 acute lymphoblastic
      leukemia, 20 lymphoma, 8 sarcoma, 15 malignant central nervous system [CNS]
      tumours). None of the LTS had been treated with growth hormone (GH). A decrease
      in final height SDS (Standard deviation score) occurred in both LTS of malignant
      CNS tumours (median height SDS at diagnosis, 0.3; range, -0.9 to 2.2; median
      final height SDS, -1.3; range, -3.9 to 1.9; p < 0.01) and LTS of lymphoma (p <
      0.05) or leukemia (p < 0.05). However, only LTS who received cranial (p < 0.05)
      or craniospinal (p < 0.001) irradiation (XRT) exhibited reduced final heights.
      LTS who had received XRT not involving the CNS or had received no XRT at all
      presented no reduction in final height. LTS of CNS tumours treated with high
      craniospinal XRT doses (24 to 56 Gy) reached lower (p < 0.01) final heights when
      compared with LTS of leukemia who received lower cranial XRT doses (18 to 24 Gy).
      Final height SDS correlated with chronological age at initiation of therapy (p <
      0.05). No correlation was found between the cumulative doses of applied
      chemotherapeutic agents and the final height of LTS. During follow-up LTS
      developed an increase in weight for height index (WFH) which occurred independent
      of XRT. In conclusion, cranial and craniospinal XRT especially in young children
      with malignancies resulted in a decrease in final height SDS. As 6 of 15 LTS of
      malignant CNS tumours exhibited a final height SDS below -2 SD, analysis of
      pituitary function and substitution of GH after diagnosis of GH deficiency should
      be considered for these patients at a young age. Others factors not directly
      related to XRT are responsible for the increased risk for obesity in LTS of
      childhood cancer.

PMID- 9628246
TI  - Thyrotropin-releasing hormone and somatostatin inhibit each others release in
      vitro in the rat retina.
AB  - The effect of thyrotropin-releasing hormone (TRH), somatostatin (SS) or
      octreotide, an analogue of SS, on release of TRH or SS from the rat retina was
      studied in vitro. The retina was incubated in medium 199 (pH 7.4) with 1.0 mg/ml
      of bacitracin (medium) for 20 min. The amount of TRH or SS release into the
      medium was measured by individual radioimmunoassays. The TRH release from the rat
      retina was inhibited significantly in a dose-related manner by the addition of SS
      or octreotide. The SS release from the retina was inhibited by TRH, and the
      inhibitory effect of TRH on SS release from the rat retina was blocked by the
      addition of anti-TRH receptor antiserum immunoglobulin fraction. The findings
      suggest an interaction between TRH and SS in the rat retina by which the addition
      of one inhibits the release of the other.

PMID- 9628247
TI  - Automated and manual assays for urinary crosslinks of collagen: which assay to
      use?
AB  - With the increasing demand for clinically useful biomarkers of bone turnover, a
      number of assays for the measurement of bone resorption markers have been
      developed. In the present study, automated (ACS: 180 DPD, Chiron Diagnostics,
      USA) and manual (DPD-ELISA, Pyrilinks-D, Metra Biosystems, USA) immunoassays for
      free DPD, and a manual immunoassay for the aminoterminal telopeptide of type I
      collagen (NTX, Osteomark, Ostex International, USA) were compared to the
      automated HPLC method for free DPD. Urine samples from a total of 538 healthy and
      diseased subjects aged 20 to 80 years were analyzed. The age and sex stratified
      reference ranges were essentially identical for the HPLC, ACS: 180 and the DPD
      ELISA, but differed from the NTX assay. Individual values for free DPD as
      generated by HPLC and immunoassay techniques were highly correlated with each
      other, whereas correlations between assays measuring free and peptide-bound
      crosslink components were less pronounced. Precision of the automated techniques
      (HPLC and ACS: 180) was superior to that of the manual immunoassays. Disease
      specific changes in crosslink excretion were similar for all assays and most
      pronounced in metastatic osteopathy, primary hyperparathyroidism and untreated
      Paget's disease of bone. We conclude that the automated assays for free DPD in
      urine, i.e. the HPLC and the ACS: 180 assay, show better analytical performance
      than the manual immunoassays studied. All techniques used in the present study
      appear to provide similar or identical clinical information. Therefore, the
      decision which assay to use largely depends on the laboratory set-up, the number
      of samples to be analysed, the turn-around time required, and the application for
      which the test should be used.

PMID- 9628248
TI  - Carbutamide--the first oral antidiabetic. A retrospect.
AB  - This work describes the history of the first oral antidiabetic in East and West
      Germany. M. Janbon and A. Loubatieres reported experimental and clinical findings
      about a blood sugar-decreasing effect of a sulphonamide derivate, sulphoisopropyl
      thiodiazol (1942). These findings, however, did not prove to be useful in the
      treatment of diabetes. In 1952 the author found a series of hypoglycemic shocks
      with the sulfonamid-urea derivate carbutamdide during clinical tests of
      infectious diseases. These were reported to the pharmaceutical company Von Heyden
      in Dresden. The head chemist E. Haack went with my files from East to West
      Germany, to Boehringer Mannheim. Without mentioning the synthesis in Dresden, he
      synthesized carbutamide in Mannheim. The hypoglycemic effect was rediscovered by
      his friend H. Franke together with J. Fuchs. It took twenty years until the
      results of the author's research were officially acknowledged.

PMID- 9628249
TI  - Leucine-rich repeat glycoproteins of the extracellular matrix.
AB  - The extracellular matrix plays an integral role in the pivotal processes of
      development, tissue repair, and metastasis by regulating cell proliferation,
      differentiation, adhesion, and migration. This review is focused on a family of
      related glycoproteins represented by at least one member in all specialized
      extracellular matrices. This family currently comprises nine members grouped
      together on the basis of their presence in the extracellular matrix and by virtue
      of a leucine-rich repeat motif that dominates the structure of the core protein.
      It is likely that most, if not all the members of this group exist as
      proteoglycans in some tissues, and thus have been termed the Small Leucine-Rich
      Proteoglycan family, or SLRPs. The leucine-rich repeat (LRR) is usually present
      in tandem array and has been described in an increasing number of proteins,
      giving rise to a LRR-superfamily. The LRR domain of the SLRP family is unique
      within the superfamily in that it is flanked by cysteine clusters, and the 24
      amino acid consensus for SLRP members is x-x-I/V/L-x-x-x-x-F/P/L-x-x-L/P-x-x-L-x
      x-L/I-x-L-x-x-N-x-I/L, where x is any amino acid. Enormous progress has been made
      in describing the membership, structure and localization of this family, and
      recently new insight has emerged into the putative function of these molecules
      not just as modulators of matrix assembly but also on their intriguing role in
      regulating cell growth, adhesion, and migration. Determination of membership,
      structure and putative function of this fascinating class of molecules is
      summarized in this review.

PMID- 9628250
TI  - Pregnancy induces complex changes in the the pattern of mRNA expression in knee
      ligaments of the adolescent rabbit.
AB  - Knee laxity has been shown to increase during human pregnancy, and the laxity of
      the rabbit medial collateral ligament also increases during pregnancy. To
      determine whether the changes in tissue function could be related to alterations
      in the regulation of gene expression for a subset of relevant molecules in
      ligaments, RNA was isolated from the medial collateral(MCL) and anterior
      cruciate(ACL) ligaments of first time pregnant adolescent rabbits. Levels of mRNA
      for matrix molecules (collagen types I and III and the proteoglycans biglycan,
      decorin, versican and lumican), proteinases and inhibitors (collagenase,
      urokinase, PAI-1 and TIMP-1, -2 and -3), growth factors (bFGF, IGF-I, TGF-beta1
      and ET-1), cytokines (IL-1beta and TNF) and enzymes responsible for important
      tissue mediators (COX-2 and iNOS) were assessed by semi-quantitative RT-PCR. In
      the MCL, levels of transcripts for all of the matrix molecules, growth factors
      and TIMPs 1 and 2 were significantly depressed at 29 days of pregnancy compared
      to age-matched non-pregnant controls. In contrast, transcripts for PAI-1 were
      elevated during pregnancy, while those for collagenase (MMP-1), urokinase, TIMP
      3, IL-1beta, TNF, COX-2 and iNOS were not statistically altered. mRNA transcript
      levels rebounded by 7 days post-partum for most genes studied, indicating that
      the changes were rapidly reversible. For some molecules, transcript levels were
      again depressed at 18 days post-partum, indicating that regulatory mechanisms
      were still not stabilized. Analysis of mRNA from the ACL also revealed changes in
      the pattern of gene expression, with some similarities and differences from the
      MCL noted. These results indicate that pregnancy induces reversible changes in
      mRNA for matrix molecules in ligaments, but differences in responsiveness exist
      between different ligaments. The complexity of the changes observed indicates
      that there is probably no simple cause and effect relationship between laxity
      changes and the molecular alterations during pregnancy.

PMID- 9628251
TI  - Gelatinase A (MMP-2) and cysteine proteinases are essential for the degradation
      of collagen in soft connective tissue.
AB  - The degradation of soft connective tissue collagen is considered to depend on the
      activity of various proteolytic enzymes, particularly those belonging to the
      group of matrix metalloproteinases and cysteine proteinases. In the present
      study, we investigated the contribution of these enzymes to this process. Using a
      general inhibitor of MMPs (SC44463), collagen degradation was strongly inhibited,
      by about 40% after 24 h and up to 80% after 72 h of culturing. Blockage of
      cysteine proteinase activity (with leupeptin or E-64) reduced breakdown at these
      time intervals by 50% and 20%, respectively. Given the abundant presence of
      gelatinases--in particular gelatinase A (MMP-2)--in the tissue, the effect of an
      inhibitor selective for gelatinases (CT1166) was studied. Gelatinase inhibition
      resulted in a dose-dependent decrease of collagen breakdown up to 90% after 48 h.
      The ability of gelatinase A to degrade collagens was demonstrated by the
      induction of breakdown in devitalized explants by addition of activated
      gelatinase A, or by activation of endogenous enzyme with 4-aminophenylmercuric
      acetate. This latter effect was not found with plasmin, an activator of MMPs
      other than gelatinase A. Finally, the relevance of gelatinase A to the in vivo
      degradation of soft connective tissue collagen was implicated by the significant
      correlation found between its activity and the collagen turnover rates of four
      soft connective tissues (tooth pulp, periodontal ligament, molar gingiva and
      skin). We conclude that collagen degradation in soft connective tissue is
      mediated by MMPs and to a lesser extent by cysteine proteinases. Our data are the
      first to attach a key role to gelatinase A in this process.

PMID- 9628252
TI  - Mitogenic and adhesive effects of tenascin-C on human hematopoietic cells are
      mediated by various functional domains.
AB  - In the adult organism, the extracellular matrix molecule tenascin-C is
      prominently expressed in the bone marrow. Bone marrow mononuclear cells can
      adhere to plastic-immobilized tenascin-C, and in the present study we have used
      bacterial expression proteins to map the domains of tenascin-C responsible for
      binding of hematopoietic cells. A strong binding site was found to be located
      within the fibrinogen-like domain, and this binding could be inhibited by
      heparin, suggesting interactions with membrane-bound heparan sulfate
      proteoglycans. A second strong binding site was identified within the fibronectin
      type III-like repeats 6-8, and was also inhibitable by heparin. Adhesion to both
      attachment sites could not be blocked by various anti-integrin antibodies. A
      third hematopoietic cell binding site is located in the fibronectin type III-like
      repeats 1-5, which harbor an RGD sequence in the third fibronectin type III-like
      repeat. Binding to this domain, however, seems to be RGD-independent, since RGD
      containing peptides could not inhibit cell binding; the addition of heparin also
      did not block adhesion to this domain. Since contradictory results had been
      reported on a proliferative effect of soluble tenascin-C, we also analyzed its
      activity on hematopoietic cells. The heterogeneous bone marrow mononuclear cells
      show a striking proliferative response in the presence of tenascin-C which is
      concentration-dependent. This result indicates a strong mitogenic activity of
      tenascin-C on primary hematopoietic cells. Using recombinant fragments of human
      tenascin-C, we identified several mitogenic domains within the tenascin-C
      molecule. These adhesive and mitogenic effects of tenascin-C suggest a direct
      functional association with proliferation and differentiation of hematopoietic
      cells within the bone marrow microenvironment.

PMID- 9628253
TI  - Identification of types II, IX and X collagens at the insertion site of the
      bovine achilles tendon.
AB  - Achilles tendinous collagen fibrils insert into the calcaneus by first passing
      through a zone that is defined histologically as fibrocartilaginous. This zone
      consists of four regions: tendon proper, non-mineralized and mineralized
      fibrocartilage and bone. The function of this zone has not yet been clearly
      defined. To gain more insight into the role of this fibrocartilaginous zone,
      collagens present in the zone of the Achilles tendon-calcaneus interface were
      isolated and characterized. Types II, IX and X collagens were identified in the
      pepsin digests of the tissue harvested from the bovine Achilles tendon-calcaneus
      interface. Western blotting using specific antisera to types II, IX and X
      collagens confirmed the identity of these collagens. Immunofluorescence
      localization placed type X collagen predominantly in the mineralized zone of the
      tendon-calcaneus junction, while type IX collagen was distributed throughout the
      the insertion site. The presence of the cartilage-specific collagens at the
      Achilles tendon-calcaneus-interface suggests that this zone is cartilaginous in
      nature. The presence of type X collagen at this junction is not clear, but our
      present findings go along with the previous report which showed that type X
      collagen is present in the mineralized zone of the medial collateral ligament
      femoral insertion site. These data suggest that type X collagen may be a resident
      of mineralized fibrocartilaginous zones of tendon or ligament-bone junctions and
      may participate in anchoring ligament or tendon to bone.

PMID- 9628254
TI  - Study of elastic fiber organization by scanning force microscopy.
AB  - Elastic fibers of beef ligamentum nuchae were observed by atomic force microscopy
      and data compared with those obtained by conventional and freeze-fracture
      electron microscopy. Fresh isolated elastin fibers as well as thin sections of
      ligament fragments, which were fixed and embedded either in relaxed or in
      stretched conditions, were analysed. The results confirm that, at least in beef
      ligamentum nuchae, elastic fibers consist of beaded filaments which can be
      oriented by stretching in the direction of the force applied. Moreover, atomic
      force microscopy revealed that these beaded filaments are laterally connected by
      periodical bridges which become more pronounced upon stretching. The data clearly
      show that elastin molecules are organized in a rather ordered array, at least at
      the super-molecular level, and a depiction of the elastin organization in beef
      ligamentum nuchae is attempted.

PMID- 9628255
TI  - The complete cDNA coding sequence for the bovine proalpha2(I) chain of type I
      procollagen.
AB  - The complete sequence of the cDNA for the pro alpha2(I) chain of bovine type I
      procollagen is presented. The encoded amino acid sequence shows 92.0% identity to
      the human pro alpha2(I) collagen chain.

PMID- 9628256
TI  - Mechanisms of neuroinflammation: Inflammation Research Association meeting, New
      York Academy of Sciences, 16 October 1997.

PMID- 9628257
TI  - Methotrexate hepatotoxicity: what is the evidence?

PMID- 9628258
TI  - Involvement and dual effects of nitric oxide in septic shock.
AB  - Bacterial endotoxin (LPS) releases many mediators such as interleukins, tumour
      necrosis factor, oxygen free radicals, toxic eicosanoids, platelet activating
      factor, and nitric oxide (NO). LPS is a potent inducer of inducible nitric oxide
      synthase (iNOS). Large amounts of NO (made by iNOS) and peroxynitrite, among
      other factors, are responsible for the late phase of hypotension, vasoplegia,
      cellular suffocation, apoptosis, lactic acidosis and multiorgan failure in
      endotoxic shock. Indeed, experimental and clinical use of NOS inhibitors, which
      do not differentiate clearly between constitutive endothelial NOS (ceNOS) and
      iNOS, prevents LPS-induced hypotension. However, many detrimental effects of such
      NOS inhibitors are also reported, including increases in pulmonary resistance,
      decreases in cardiac output and organ perfusion, and even an increase in
      mortality of experimental animals. We believe that, in lungs, NO made by ceNOS
      plays a protective role against the pneumotoxic effects of LPS-released lipids
      such as thromboxane, leukotrienes and PAF. This is why selective iNOS inhibitors
      like aminoguanidine or thiourea derivatives might be preferred over nonselective
      NOS inhibitors for the treatment of septic shock. However, since iNOS-derived NO
      seems to have more than just a destructive action, the selective iNOS inhibition
      may be not as beneficial as expected. Accordingly, inhalation of NO gas or NO
      donors in septic shock might be a complementary treatment to the use of NOS
      inhibitors.

PMID- 9628259
TI  - Interleukin-13 increases prostaglandin E2 (PGE2) production by normal human
      polymorphonuclear neutrophils by enhancing cyclooxygenase 2 (COX-2) gene
      expression.
AB  - OBJECTIVE: To investigate whether interleukin-13 (IL-13) can affect arachidonic
      acid metabolism and phagocytic activity of normal human polymorphonuclear
      neutrophils (PMN). METHODS: Normal human PMN (1 x 10(6) cells/ml) were incubated
      with different concentrations of IL-13 (0.1-10 ng/ml) for a variety of times (30
      120 min). Phagocytosis and intracellular cyclooxygenase-2 (COX-2) were detected
      by flow cytometry. The expression of COX-1 and COX-2 mRNA was detected by RT-PCR.
      The concentration of PGE2 in the PMN cultured supernatants was determined by EIA.
      RESULTS: We found that IL-13 at an optimal concentration of 1 ng/ml significantly
      enhanced COX-2 gene expression and PGE2 production (121.57 +/- 22.17 pg/ml in IL
      13 stimulation vs. 73.16 +/- 11.72 pg/ml in controls) by PMN. In addition, IL-13
      stimulated PMN phagocytosis via increased complement receptor type 1 (CR1) and
      type 3 (CR3), but not IgG Fcgamma receptor type 3 (FcgammaRIII). The cytoplasmic
      neutral esterase activity of PMN was also enhanced by IL-13 stimulation for 24 h.
      CONCLUSIONS: These results suggest that IL-13 can stimulate PMN and modulates the
      inflammatory reactions via the cyclooxygenase pathway.

PMID- 9628260
TI  - Anthralin stimulates keratinocyte-derived proinflammatory cytokines via
      generation of reactive oxygen species.
AB  - OBJECTIVE AND DESIGN: Topical application of anthralin, used in the treatment of
      psoriasis, is often accompanied by severe skin inflammation, presumably due to
      free radical products of the drug. The role of inflammatory cytokines and their
      induction by anthralin-derived reactive oxygen species were studied in cultures
      of normal human keratinocytes (NHKs). MATERIALS AND METHODS: Anthralin was added
      to cultures of NHKs in the presence or absence of various antioxidants, including
      superoxide dismutase, tetramethylthiourea, N-acetylcysteine and vitamin E and
      relative changes in cytokine secretion and in the number of mRNA transcripts were
      examined. In addition, NHKs were either treated with neutralizing antibodies to
      tumor necrosis factor (TNF)-alpha or transfected with a CAT-linked IL-8 promoter
      to establish the direct effects of anthralin on chemokine synthesis. RESULTS:
      Anthralin, at concentrations between 5 microM and 25 microM, caused a marked
      increase in granulocyte macrophage-colony stimulating factor (GM-CSF),
      interleukin (IL)-6, IL-8 and TNFalpha synthesis that was selectively inhibited by
      specific antioxidants. Furthermore, anthralin induced chemokine secretion without
      the need of primary cytokines. CONCLUSIONS: Taken together, these studies suggest
      that oxygen radicals generated from anthralin are responsible for the induction
      of inflammatory cytokines which, in turn contributes to their dermal toxicity.

PMID- 9628261
TI  - Anti-inflammatory effect of YPE-01, a novel diarylheptanoid derivative, on dermal
      inflammation in mice.
AB  - OBJECTIVE AND DESIGN: We investigated the anti-inflammatory effect of YPE-01, a
      novel diarylheptanoid derivative in vitro and in vivo. MATERIAL: In the in vitro
      study, rat basophilic leukemia (RBL-1) cells were used. For the in vivo study,
      ICR and ddY mice (male, 7 weeks old) were used. TREATMENT: In the in vitro study,
      the supernatant of RBL-1 cells lysate was incubated with 50 microM arachidonic
      acid (AA) and 0.01-100 microM test drugs for 15 min. RBL-1 cells were
      preincubated with 0.01-100 microM test drugs for 10 min before incubation with
      0.5 microM calcium ionophore A23187 for 10 min. In the in vivo study, YPE-01 (0.1
      3 mg/ear) was applied to the ear of mice at the same time as a 12-O
      tetradecanoylphorbol 13-acetate (TPA) application or 1 h before an AA
      application. METHODS: In the in vitro study, the amounts of 5
      hydroxyeicosatetraenoic acid and leukotrienes were measured by high-performance
      liquid chromatography and an enzyme immunoassay, respectively. In the in vivo
      study, a circular tissue sample from the ear of the mice was weighed. Statistical
      analysis was done using Dunnett's test. RESULTS: YPE-01 inhibited the 5
      lipoxygenase activity (IC50, 0.28 microM) and the leukotriene B4 (IC50, 0.035
      microM) and C4 (IC50, 0.046 microM) production by RBL-1 cells without any
      inhibition of cyclooxygenase activity in vitro. The topical application of YPE-01
      significantly suppressed both the AA- and TPA-induced ear edemas in vivo.
      CONCLUSIONS: YPE-01 is a selective 5-lipoxygenase inhibitor with a suppressive
      effect against dermal inflammation.

PMID- 9628262
TI  - Inhibitory effects of JTE-522, a novel prostaglandin H synthase-2 inhibitor, on
      adjuvant-induced arthritis and bone changes in rats.
AB  - OBJECTIVE AND DESIGN: To investigate the effect of JTE-522, a novel selective
      prostaglandin H synthase (PGHS)-2 inhibitor, on adjuvant-induced arthritis and
      bone changes. SUBJECTS: Male Lewis rats at 8 weeks old were immunized with heat
      killed mycobacteria. TREATMENT: JTE-522 (0.1-30 mg/kg) and indomethacin (0.1-3
      mg/kg) were administered orally once-daily after immunization. METHODS: Paw
      swelling, bone changes in arthritic paws and vertebrae, urinary levels of
      deoxypyridinoline and pyridinium crosslinks, and the incidence of gastric lesions
      were determined in arthritic rats. RESULTS: JTE-522 (from 0.3 mg/kg) suppressed
      the development of paw swelling, and also reduced bone damage (score and bone
      mineral density) in arthritic paws and the urinary excretion of deoxypyridinoline
      and pyridinium crosslinks. However, JTE-522 did not cause gastric lesions even at
      30 mg/kg in arthritic rats. CONCLUSIONS: These results suggest that JTE-522
      possesses potent anti-arthritic activities and suppressive activity on
      inflammatory bone resorption without gastric side effects.

PMID- 9628263
TI  - Histamine, xanthine oxidase generated oxygen-derived free radicals and
      Helicobacter pylori in gastroduodenal inflammation and ulceration.
AB  - OBJECTIVE: The relationship between Helicobacter pylori (H. pylori), xanthine
      oxidase (XO)-induced oxygen derived free radicals (ODFR) and histamine in the
      induction of human gastroduodenal disorders was investigated. PATIENTS AND
      METHODS: Histamine concentration, XO and xanthine dehydrogenase (XD) activities
      were measured in endoscopically obtained biopsies from 66 symptomatic patients.
      RESULTS: H. pylori infection was associated with lower oxyntic and duodenal
      histamine in 'normal' controls (group N) (p < 0.002 and p < 0.05, respectively).
      Patients with gastroduodenal disease tended to have reduced mucosal concentration
      of histamine, but comparing H. pylori positive and negative patients, infection
      did not lead to a further fall in histamine concentration. H. pylori positive
      duodenal ulcer (DU) patients tended to have higher XO activity than group N (p =
      0.051) and had a significantly lowered activity of XD, the precursor of XO (p' <
      0.05). Histamine concentration at the ulcer-edge was lower while XO activity was
      higher than in the distant normal mucosa (p < 0.05, respectively). Gastritis
      (group GL) with H. pylori also had lower XD than H. pylori positive group N (p' <
      0.025) but no corresponding rise in XO activity. In group N, duodenal mucosal
      histamine and XD activity were inversely related (Rs = -0.51, p < 0.025).
      CONCLUSIONS: These findings support the hypothesis that histamine, xanthine
      oxidase related ODFR, and H. pylori may be closely associated in the
      manifestations of chronic duodenal ulcer.

PMID- 9628264
TI  - Inhibition of angiogenesis on glycated collagen lattices.
AB  - Advanced glycation endproduct (AGE) accumulation in extracellular matrix proteins
      has been demonstrated in diabetic patients with a significant correlation with
      the severity of diabetic complications. AGE accumulation induces matrix protein
      cross-link formation, resulting in an increased stiffness of matrix fibres and
      the reduction of the susceptibility of matrix proteins to proteolytic
      degradation. We examined whether glycation-induced collagen cross-linking may
      affect vascular endothelial cell behaviours such as invasion, proliferation and
      differentiation, using the in vitro angiogenesis model of capillary-like
      structure formation in three-dimensional matrices of collagen type I. Endothelial
      cells cultured on collagen gel with angiogenic factors (the combination of
      fibroblast growth factor-2 and vascular endothelial growth factor) invaded the
      underlying collagen matrix, and organized capillary-like cord structures in the
      gel. We found that endothelial cell invasion into glycated collagen gel was
      significantly attenuated without any effect on proteinase activity including cell
      associated plasminogen activator and matrix metalloproteinase in the conditioned
      medium. In addition, subsequent capillary-like cord formation was also inhibited
      in glycated collagen gel. In contrast, endothelial cell proliferation was
      enhanced on glycated collagen gel with or without angiogenic factors compared
      with control collagen gel. These results suggest that the structural alterations
      of extracellular matrix proteins through the glycation-induced cross-link
      formation affect the interaction between endothelial cell and extracellular
      matrix, resulting in the impairment of an adequate neovascularization in diabetic
      patients.

PMID- 9628265
TI  - Retrovirus-mediated gene transfer targeted to retinal photocoagulation sites.
AB  - Diabetic retinopathy is a major cause of acquired blindness due to the
      development of retinal neovascularization and associated traction retinal
      detachment. It is commonly treated with retinal photocoagulation therapy;
      however, progression to blindness remains a significant problem. To determine the
      feasibility of adjunctive anti-angiogenic gene therapy, we evaluated the
      capability of retroviral vectors, which transfer exogenous genes only into
      dividing cells, to transfer and express a beta-galactosidase gene selectively
      into photocoagulation sites. Thirty-five rabbits received 30 retinal
      photocoagulation burns in the right eye followed 2 days later by beta
      galactosidase (G1nBgSvNa) or control (G1XSvNa) vector injection into the
      subretinal space. Beta-galactosidase expression was observed in the
      photocoagulation sites from 5 days after vector administration (31.7+/-7.0%) to
      12 weeks (6.7+/-3.4%). Immunohistochemical studies of the treated retinas using
      antibody Ber-MAC3 and anti-cytokeratin antibodies revealed that transduced cells
      were macrophages and retinal pigment epithelial cells. To determine feasibility
      in a primate, two monkeys received 10 laser burns in the macula superior to the
      fovea followed 2 days later by G1nBgSvNa vector. beta-galactosidase expression
      was found in photocoagulation sites and foveal retina was well preserved. We
      conclude that gene transfer to retinal photocoagulation sites provides stable
      expression of the transduced gene with relatively high efficiency. This
      feasibility study suggests the possibility of transferring genes encoding for
      anti-angiogenic factors into photocoagulation sites to improve the efficacy of
      laser photocoagulation therapy.

PMID- 9628266
TI  - High glucose-induced mesangial cell altered contractility: role of the polyol
      pathway.
AB  - Glomerular mesangial cells cultured in high glucose conditions display impaired
      contractile responsiveness. It was postulated that glucose metabolism through the
      polyol pathway leads to altered mesangial cell contractility involving protein
      kinase C. Rat mesangial cells were growth-arrested for 24 h with 0.5% fetal
      bovine serum in either normal (5.6 mmol/l) or high (30 mmol/l) glucose
      concentrations or high glucose plus the aldose reductase inhibitor, ARI-509 (100
      micromol/l). The reduction of cell planar surface area (contraction) in response
      to endothelin-1 (0.1 micromol/l), or to phorbol 12-myristate 13-acetate (50
      pmol/l), was studied by videomicroscopy. In response to endothelin-1, mesangial
      cells in normal glucose contracted to 52+/-3% of initial planar area. In high
      glucose, the significantly (p < 0.05) smaller cell size and no contractile
      responsiveness to endothelin-1 were normalized with ARI-509. Membrane-associated
      diacylglycerol, measured by a kinase specific 32P-phosphorylation assay, in high
      glucose was unchanged after 3 h, but significantly increased (p < 0.05) after 24
      h which was normalized with ARI-509. Protein kinase C activity, measured by in
      situ 32P-phosphorylation of the epidermal growth factor receptor substrate was:
      increased by 32% at 3 h of high glucose, unchanged by ARI-509; and decreased
      significantly (p < 0.05) at 24 h compared to cells in normal glucose, normalized
      by ARI-509. Total cellular protein kinase C-alpha, -delta and -epsilon, analysed
      by immunoblotting, were unchanged in high glucose at 24 h. Only protein kinase C
      epsilon content was reduced by ARI-509 in both normal and high glucose.
      Therefore, high glucose-induced loss of mesangial cell contractility,
      diacylglycerol accumulation and altered protein kinase C activity are mediated
      through activation of the polyol-pathway, although no specific relationship
      between elevated diacylglycerol and protein kinase C activity was observed. In
      high glucose, altered protein kinase C function, or another mechanism related to
      the polyol pathway, contribute to loss of mesangial cell contractile
      responsiveness.

PMID- 9628267
TI  - Tissue ascorbic acid and polyol pathway metabolism in experimental diabetes.
AB  - Previous studies demonstrating reduced plasma concentrations of ascorbic acid
      (AA) in diabetes and interactions between this vitamin and biochemical mechanisms
      such as synthesis of structural proteins, oxidative stress, polyol pathway and
      nonenzymatic glycation of proteins suggest that disturbed AA metabolism may be
      important in the pathogenesis of diabetic microangiopathy. However, limited
      information is available on the concentration of AA in tissues which develop
      diabetic complications. This study demonstrates reduced renal but not sciatic
      nerve or plasma AA concentration in two animal models of insulin-dependent
      diabetes mellitus, namely the STZ-diabetic rat and the spontaneously diabetic BB
      rat. Decreased lens AA concentration was also observed in STZ-diabetic rats.
      Improvement of glycaemic control by insulin treatment (albeit insufficient to
      achieve normoglycaemia) partially corrected lens and renal AA concentration in
      STZ-diabetic rats. AA treatment increased kidney and lens AA concentrations of
      STZ-diabetic and non-diabetic rats and corrected the abnormalities observed for
      untreated diabetic rats. Sciatic nerve AA concentration was not increased by AA
      treatment in any group. Tissue ratios of dehydroascorbic acid (DHAA)/AA, one
      index of oxidative stress, were not different between the diabetic and non
      diabetic groups and were unaltered by AA supplementation. AA treatment of STZ
      diabetic rats had no effect on elevated tissue concentrations of glucose,
      sorbitol and fructose or reduced myo-inositol concentration. The effect of
      reduced tissue AA levels in diabetes on either collagen synthesis or ability to
      combat increased free radical production is not known. However, correction of
      abnormal kidney and lens AA concentrations in experimental diabetes by AA
      supplementation suggests that if AA does have a role in the development or
      progression of the renal and ocular complications of diabetes, this treatment
      could be beneficial.

PMID- 9628268
TI  - Failure of leptin to affect basal and insulin-stimulated glucose metabolism of
      rat skeletal muscle in vitro.
AB  - Studies on different isolated tissues have provided evidence that leptin may
      directly modulate cellular glucose handling. The present study was performed to
      elucidate leptin's action on basal and insulin-stimulated glucose metabolism in
      native muscle tissue, which under physiological circumstances is the
      quantitatively most important target tissue of insulin. Isolated rat soleus
      muscle strips were incubated for 1 h in the absence or presence of leptin (0, 1,
      10, or 100 nmol/l) under basal or insulin-stimulated conditions (10 nmol/l). No
      effects of leptin were found on the rates of 3H-2-deoxy-glucose transport (basal:
      control, 314+/-14; 1 nmol/l leptin, 320+/-17; 10 nmol/l leptin, 314+/-13; 100
      nmol/l leptin, 322+/-16; insulin-stimulated: control, 690+/-33; 1 nmol/l leptin,
      691+/-29; 10 nmol/l leptin, 665+/-26; 100 nmol/l leptin, 664+/-27; cpm x mg(-1) x
      h(-1); NS vs respective control) and on net glucose incorporation into glycogen
      (basal: control, 1.75+/-0.18; 1 nmol/l leptin, 2.01+/-0.13; 10 nmol/l leptin,
      1.92+/-0.11; 100 nmol/l leptin, 1.81+/-0.13; insulin-stimulated: control, 5.98+/
      0.40; 1 nmol/l leptin, 5.93+/-0.30; 10 nmol/l leptin, 5.46+/-0.25; 100 nmol/l
      leptin, 5.85+/-0.30; micromol x g(-1) x h(-1); NS vs respective control). In
      parallel, leptin failed to affect rates of aerobic and anaerobic glycolysis as
      well as muscle glycogen content. Further experiments revealed that the inability
      of leptin to directly affect muscle glucose handling prevailed independently of
      muscle fiber type (soleus and epitrochlearis muscle), of ambient insulin
      concentrations (0-30 nmol/l), and of leptin exposure time (1 h or 6 h). Thus, our
      findings fail to support speculations about a physiological role of direct
      insulin-mimetic or insulin-desensitizing effects of leptin on skeletal muscle
      tissue.

PMID- 9628269
TI  - Regulation of GAD expression in rat pancreatic islets and brain by gamma-vinyl
      GABA and glucose.
AB  - Glutamic acid decarboxylase (GAD) is an important autoantigen in insulin
      dependent diabetes mellitus (IDDM), but little is known about its regulation and
      function in islet cells. We investigated the effects of the GABA-transaminase
      inhibitor gamma-vinyl-GABA (GVG) on GAD expression in rat islets and brain in
      vitro and in vivo. In islets incubated in high glucose culture medium there was
      an increase in GAD activity, GAD65 and GAD67 protein levels compared to low
      glucose conditions; however, even in high glucose, GVG still significantly
      suppressed GAD activity and GAD67 expression. Our observations suggest that
      glucose and GVG act on GAD in islets through different mechanisms. Quantitative
      immunohistochemistry of pancreatic sections from rats treated with GVG in vivo
      using novel monoclonal antibodies specific for GAD65 and GAD67, showed a decrease
      in GAD67 expression (p < 0.005) relative to untreated rats. The effects of GVG on
      rat pancreatic islets were very similar to those observed in brain of rats
      treated with GVG in vivo. In homogenates of cerebral tissue from GVG treated rats
      containing both membrane-bound and soluble protein GAD67 levels were
      significantly decreased while GAD65 levels were not significantly changed
      compared to untreated rats. In contrast, in homogenates of cerebral tissues
      containing only soluble cytosolic protein, GVG-treatment was also significantly
      found to decrease GAD65 levels. Taken together, these results suggest that GVG
      potentially could be of use to decrease GAD expression in islet cells and
      consequently to deviate/inhibit the autoimmune response against the beta cells
      seen in IDDM.

PMID- 9628270
TI  - Delay of type I diabetes in high risk, first degree relatives by parenteral
      antigen administration: the Schwabing Insulin Prophylaxis Pilot Trial.
AB  - The Schwabing Insulin Prophylaxis Trial is a randomised, controlled pilot study
      designed to examine whether insulin therapy can delay or prevent the clinical
      onset of Type I diabetes in high risk first degree relatives of people with the
      disease. First degree relatives of patients with Type I diabetes, who were aged 4
      years or more, had an islet cell antibody (ICA) value more than 20 Juvenile
      Diabetes Foundation Units (JDF-U), a reduced first phase insulin response (FPI)
      to an i.v. glucose tolerance test less than the 5th centile, and a normal oral
      glucose tolerance test were eligible for the trial. Between January 1989 and
      October 1995, 1736 relatives of patients with Type I diabetes were screened for
      ICA. We identified 64 cases (3.7%) with ICA values more than 20 JDF-U. Of ICA
      positive relatives, 17 (27%) had a low FPI and were eligible for enrolment. Of
      these 14 agreed to participate, of whom 7 were randomised to the treatment group
      and 7 to the control group. In the treatment group, human insulin was
      administered i.v. by continuous infusion for 7 days, followed by daily s. c.
      injections for 6 months. Intravenous insulin infusions were repeated every 12
      months. In the treatment group 3 of the 7 individuals (follow-up from time of
      eligibility: 2.3 to 7.1 years) and in the control group 6 of the 7 untreated
      individuals (1.7 to 7.1 years) developed clinical diabetes. Life table analysis
      showed that clinical onset of Type I diabetes was delayed in insulin-treated
      subjects compared with control subjects (means+/-SEM diabetes-free survival:
      5.0+/-0.9 years vs 2.3+/-0.7 years, p < 0.03). Insulin levels after i.v. glucose
      increased in the first year of intervention therapy. Titres of ICA, and
      antibodies to glutamic acid decarboxylase, and tyrosine phosphatase-like protein
      IA2 remained unchanged. These data suggest that insulin prophylaxis can delay the
      onset of overt diabetes in high risk relatives. This is encouraging in view of 1)
      the continuing American Diabetes Prevention Trial, which is currently testing the
      effect of parenteral insulin in a large nation-wide study and 2) the initiation
      of pilot trials to determine whether new antigen-specific intervention is more
      effective in delaying the clinical onset of Type I diabetes.

PMID- 9628271
TI  - Contributions of age, gender and insulin administration to weight gain in
      subjects with IDDM.
AB  - Overweight in insulin-dependent diabetes mellitus (IDDM) has been repeatedly
      reported, especially in girls during adolescence. Potential pathophysiologic
      factors include tight metabolic control, insulin dose, treatment regimen, puberty
      and genetics. A standardized data-base from all IDDM patients treated at our
      institution was evaluated. IDDM patients with hypothyroidism or celiac's disease
      as well as all records from the first year of diabetes were excluded, resulting
      in a total of 427 patients (2454 patient-years) available for analysis. BMI and
      SD-score for BMI based on the Zurich longitudinal growth study were evaluated.
      Standardized BMI was higher in pubertal children ( + 1.07+/-0.06) compared to
      prepubertal children (+ 0.68+/-0.07; p < 0.002). This increase was present both
      for boys and girls. Increasing overweight during puberty was found irrespective
      of the age at diagnosis of diabetes (prepubertal or pubertal). The daily dose of
      insulin and the long-term metabolic control had only a minor impact on the
      development of overweight. In contrast, in pubertal children, SDS-BMI was
      significantly higher in patients on intensified insulin regimens (3 or 4 daily
      injections) compared to patients with 2 injections (p < 0.05). These data
      demonstrate that both boys as well as girls with IDDM develop overweight during
      puberty. Multiple injection therapy, not daily dose of insulin or the level of
      metabolic control achieved, was the main predictor of weight gain. This finding
      may be explained by increased caloric intake due to the flexibility allowed by
      intensified treatment.

PMID- 9628272
TI  - Measuring pre-hepatic insulin secretion using a population model of C-peptide
      kinetics: accuracy and required sampling schedule.
AB  - The accuracy of calculations of pre-hepatic insulin secretion were investigated,
      to provide independent validation of a population model of C-peptide kinetics.
      The effects of sampling frequency were also assessed. Five normal subjects (aged
      28 to 43 years; BMI (kg/m2) 20.5 to 24.5) and five subjects with non-insulin
      dependent diabetes mellitus (NIDDM) treated by diet alone (aged 34 to 57 years;
      BMI 22.6 to 25.6) were given a variable intravenous infusion of biosynthetic
      human C-peptide (BHCP) (t=-60 to 240 min) mimicking meal stimulated C-peptide
      secretion, with short-term oscillations (peak approximately every 12 min)
      superimposed on the infusion profile. Plasma C-peptide was measured every 5 min
      (t=0 to 240 min). The BHCP infusion was reconstructed from C-peptide measurements
      using a population model of C-peptide kinetics and a deconvolution method. Bias,
      defined as the percentage difference between the total amount of calculated BHCP
      and the total amount of infused BHCP (t=0 to 240 min), indicated that overall C
      peptide secretion can be measured with 14% [95% confidence interval (CI) -11 to
      39%] and 21% (95% CI -3 to 45%) accuracy in normal subjects and subjects with
      NIDDM respectively. Accuracy was not reduced by reducing the sampling frequency
      to every 30 min. The root mean square error, measuring the average deviation
      between the infused and normalised calculated BHCP profiles, was also independent
      of the sampling frequency [mean (95% CI) 0.9 (0.3 to 1.6) pmol/kg per min in
      normal subjects; 1.0 (0.9 to 1.1) pmol/kg per min in subjects with NIDDM].
      Deconvolution employing a population model of C-peptide kinetics can be used to
      estimate postprandial total C-peptide secretion with biases of 14% and 22%
      respectively in normal subjects and subjects with NIDDM. Plasma C-peptide samples
      need only be drawn every 30 minutes.

PMID- 9628273
TI  - Insulin resistance characterizes glucose uptake in skeletal muscle but not in the
      heart in NIDDM.
AB  - Skeletal muscle insulin resistance and coronary heart disease (CHD) often precede
      non-insulin-dependent diabetes mellitus (NIDDM). A recent study showed the
      myocardium of patients with CHD to be insulin resistant, independent of blood
      flow. We determined whether myocardial insulin resistance is a feature of NIDDM
      patients with no CHD. Skeletal muscle and myocardial glucose uptake were
      determined in 10 patients with NIDDM and 9 age- and weight-matched normal men of
      similar age and body mass index men using [18F]-2-fluoro-2-deoxy-D-glucose and
      positron emission tomography under normoglycaemic hyperinsulinaemic conditions.
      Whole body glucose uptake, as determined by the euglycaemic clamp technique, was
      significantly lower in the patients with NIDDM (35+/-3 micromol/kg body weight
      min) than the normal subjects (45+/-3 micromol/kg body weight x min, p < 0.02).
      Insulin-stimulated femoral muscle glucose uptake was significantly lower in the
      patients with NIDDM (71+/-6 micromol/kg muscle x min) than in the normal subjects
      (96+/-5 micromol/kg muscle x min, p < 0.01). Whole body glucose uptake was
      correlated with femoral muscle glucose uptake in the entire group (r=0.76, p <
      0.001), in patients with NIDDM and in normal subjects. Rates of insulin
      stimulated myocardial glucose uptake were comparable between the patients with
      NIDDM (814+/-76 micromol/kg muscle min) and the normal subjects (731+/-63
      micromol/kg muscle min, p > 0.4). Whole body or femoral muscle, and myocardial
      glucose uptake were not correlated in all subjects, patients with NIDDM or normal
      subjects. We conclude that insulin resistance of the myocardium is not a feature
      of uncomplicated NIDDM.

PMID- 9628274
TI  - Various phosphodiesterase subtypes mediate the in vivo antilipolytic effect of
      insulin on adipose tissue and skeletal muscle in man.
AB  - The antilipolytic effect of insulin on human abdominal subcutaneous adipose
      tissue and skeletal muscle during local inhibition of cAMP-phosphodiesterases
      (PDEs) was investigated in vivo, by combining microdialysis with a euglycaemic,
      hyperinsulinaemic clamp. During hyperinsulinaemia, the glycerol concentration
      decreased by 40% in fat and by 33% in muscle. Addition of the selective PDE3
      inhibitor amrinone abolished the insulin-induced decrease in adipose glycerol
      concentration, but did not influence the glycerol concentration in skeletal
      muscle. Nor did the PDE4-selective inhibitor rolipram or the PDE5-selective
      inhibitor dipyridamole influence the insulin-induced decrease in muscle tissue
      glycerol. However, the non-selective PDE-inhibitor theophylline counteracted the
      antilipolytic action of insulin at both sites. The specific activity of PDEs was
      also determined in both tissues. PDE3-activity was 36.8+/-6.4 pmol x min(-1) x
      mg(-1) in adipose tissue and 3.9+/-0.5 pmol x min(-1) x mg(-1) in muscle. PDE4
      activity in skeletal muscle was high, i.e., 60.7+/-10.2 pmol x min(-1) x mg(-1)
      but 8.5 pmol x min(-1) x mg(-1) or less in adipose tissue. In conclusion, insulin
      inhibits lipolysis in adipose tissue and skeletal muscle by activation of
      different PDEs, suggesting a unique metabolic role of muscle lipolysis.

PMID- 9628275
TI  - Insulin-induced vasodilatation and endothelial function in obesity/insulin
      resistance. Effects of troglitazone.
AB  - Insulin resistance is associated with a decreased vasodilator response to
      insulin. Because insulin's vasodilator effect is nitric oxide dependent, this
      impairment may reflect endothelial dysfunction. Troglitazone, an insulin
      sensitiser, might thus improve insulin-dependent and/or endothelium-dependent
      vascular function in insulin resistant obese subjects. For 8 weeks, fifteen obese
      subjects were treated with either 400 mg troglitazone once daily or placebo, in a
      randomised, double-blind, cross-over design. At the end of each treatment period,
      we measured forearm vasodilator responses (plethysmography) to intra-arterial
      administered acetylcholine and sodium nitroprusside; insulin sensitivity and
      insulin-induced vascular and neurohumoral responses (clamp); vasoconstrictor
      responses to NC-monomethyl-L-arginine (L-NMMA) during hyperinsulinaemia; and
      ambulatory 24-h blood pressure (ABPM). Baseline data (placebo) of obese subjects
      were compared with those obtained in lean control subjects. Obese subjects were
      insulin resistant compared with leans (whole-body glucose uptake: 26.8+/-3.0 vs.
      53.9+/-4.3 [tmol kgl min-, p < 0.001). Troglitazone improved whole-body glucose
      uptake (to 31.9+/-3.3 micromol x kg(-1) x min(-1) , p=0.028), and forearm glucose
      uptake (from 1.09+/-0.54 to 2.31+/-0.69 micromol dL(-1) x min(-1), p=0.006).
      Insulin-induced vasodilatation was blunted in obese subjects (percent increase in
      forearm blood flow (FBF) in lean 66.5+/-23.0%, vs. 10.1+/-11.3% in obese,
      p=0.04), but did not improve during troglitazone. Vascular responses to
      acetylcholine, sodium nitroprusside and L-NMMA did not differ between the obese
      and lean group, nor between both treatment periods in the obese individuals. In
      conclusion, in insulin resistant obese subjects, endothelial vascular function is
      normal despite impaired vasodilator responses to insulin. Troglitazone improved
      insulin sensitivity but it had no effects on endothelium-dependent and 
      independent vascular responses. These data do not support an association between
      insulin resistance and endothelial function.

PMID- 9628276
TI  - The effect of single doses of pramlintide on gastric emptying of two meals in men
      with IDDM.
AB  - In a previous study we have shown that an intravenous infusion of pramlintide (an
      analogue of human amylin) delayed gastric emptying, but the dose of pramlintide
      was supraphysiological in relation to the amylin response to food in non-diabetic
      subjects. The purpose of this study was to examine the dose response relationship
      of subcutaneous injections of pramlintide on gastric emptying and to determine
      whether administration of the drug before one meal has an impact on the
      subsequent meal. Eleven men with insulin-dependent diabetes mellitus were studied
      in a double-blind, randomised, four-way crossover design. None had autonomic
      neuropathy. Euglycaemia was maintained overnight before the study day. At -30 min
      the patients self-injected their usual morning insulin and at -15 min they
      injected the study drug (either placebo or 30, 60 or 90 microg pramlintide)
      subcutaneously. At 0 min they ate a standard meal consisting of a pancake,
      labelled with 99mTc, and a milkshake containing 3-ortho-methylglucose (3-OMG).
      Gastric emptying images were obtained for the next 8 h. At 240 min the subjects
      ate a similar meal, but on this occasion the pancake was labelled with (111)In.
      All three doses of pramlintide delayed emptying of the solid component of the
      first meal (p < 0.004) with no significant difference between the drug doses.
      There were no differences between placebo and pramlintide after the second meal.
      All three doses of pramlintide resulted in a prolongation in the time to peak
      plasma 3-OMG level (p < 0.0001) after the first meal but there was no difference
      after the second meal.

PMID- 9628278
TI  - Increased levels of circulating free insulin-like growth factors in patients with
      non-islet cell tumour hypoglycaemia.
AB  - Non-islet cell tumour hypoglycaemia (NICTH) is characterised by severe and
      recurrent fasting hypoglycaemia, and is usually caused by secretion of insulin
      like growth factor-II (IGF-II) by the tumour. This induces secondary changes in
      the circulating levels of insulin, growth hormone (GH), and the IGF-binding
      proteins (IGFBPs), resulting in an increased insulin-like hypoglycaemic activity
      of IGF-II. A participating role of IGF-I is not established. We measured serum
      levels of free IGF-I and free IGF-II, total IGF-I, total IGF-II, big IGF-II and
      IGFBP-1, IGFBP-2 and IGFBP-3 in patients with NICTH before (n=14) and after
      surgical removal of the tumour (n=3). A control group (n=20) was included for
      comparison. In NICTH patients, free IGF-II was 20-fold increased (26.8+/-8.1
      [mean+/-SEM] vs. 1.3+/-0.1 microg/l), and free IGF-I was four fold increased
      (2.8+/-0.4 vs. 0.7+/-0.1 microg/l), as compared to control subjects (p < 0.0001).
      In accordance with earlier observations levels of total IGF-I, total IGF-II, and
      IGFBP-3 were decreased, whereas IGFBP-1 and IGFBP-2 were increased in NICTH (all
      p-values < 0.05). The highly elevated levels of free IGF-I and free IGF-II most
      likely imply a considerable hypoglycaemic insulin-like activity, and may, by
      negative feedback explain the marked suppression of the GH/IGF-I axis observed in
      NICTH. Finally, free IGF-II seems to be a powerful biochemical marker in the
      diagnosis of NICTH.

PMID- 9628277
TI  - The effects of coenzyme Q10 treatment on maternally inherited diabetes mellitus
      and deafness, and mitochondrial DNA 3243 (A to G) mutation.
AB  - The characteristic clinical features of diabetes mellitus with mitochondrial DNA
      (mtDNA) 3243(A-G) mutation are progressive insulin secretory defect, neurosensory
      deafness and maternal inheritance, referred to as maternally inherited diabetes
      mellitus and deafness (MIDD). A treatment for MIDD to improve insulin secretory
      defects and reduce deafness has not been established. The effects of coenzyme Q10
      (CoQ10) treatment on insulin secretory response, hearing capacity and clinical
      symptoms of MIDD were investigated. 28 MIDD patients (CoQ10-DM), 7 mutant
      subjects with impaired glucose tolerance (IGT), and 15 mutant subjects with
      normal glucose tolerance (NGT) were treated daily with oral administration of 150
      mg of CoQ10 for 3 years. Insulin secretory response, blood lactate after
      exercise, hearing capacity and other laboratory examinations were investigated
      every year. In the same way we evaluated 16 MIDD patients (control-DM), 5 mutant
      IGT and 5 mutant NGT subjects in yearly examinations. The insulin secretory
      response assessed by glucagon-induced C-peptide secretion and 24 h urinary C
      peptide excretion after 3 years in the CoQ10-DM group was significantly higher
      than that in the control-DM group. CoQ10 therapy prevented progressive hearing
      loss and improved blood lactate after exercise in the MIDD patients. CoQ10
      treatment did not affect the diabetic complications or other clinical symptoms of
      MIDD patients. CoQ10 treatment did not affect the insulin secretory capacity of
      the mutant IGT and NGT subjects. There were no side effects during therapy. This
      is the first report demonstrating the therapeutic usefulness of CoQ10 on MIDD.

PMID- 9628279
TI  - ACE inhibitors, diabetes and cardiovascular disease.

PMID- 9628280
TI  - Do ACE inhibitors offer specific benefits in the antihypertensive treatment of
      diabetic patients? 17 years of unfulfilled promises.

PMID- 9628281
TI  - Identification of a single nucleotide insertion polymorphism in the upstream
      region of the insulin promoter factor-1 gene: an association study with diabetes
      mellitus.
AB  - Insulin promoter factor 1 (IPF1) is a key factor both for the regulation of
      insulin gene expression and for the development of the pancreas. In this study 88
      patients with non-insulin-dependent diabetes mellitus (NIDDM) who were diagnosed
      as diabetic at less than 40 years of age, 55 patients with insulin-dependent
      diabetes (IDDM), and 67 normal control subjects were analysed for variants in the
      upstream region of the IPF1 gene by direct sequencing. A novel single nucleotide
      insertion polymorphism was found in a guanine triplet at 108 bp upstream of the
      translation start site. The G insertion allele (G4 allele) was found to be common
      in the Japanese population, at a frequency of 0.50. The prevalence of G3
      homozygotes was higher in IDDM patients (35%) and lower in NIDDM patients (17%)
      than in normal control subjects (28%, p=0.049). In the NIDDM group, the ratio of
      insulin treatment tended to be higher in subjects homozygous for the G3 allele,
      although the genotype was not significantly associated with basal C-peptide
      levels. The polymorphism is unlikely to be a major contributor to the insulin
      deficiency of diabetes. However, the polymorphic locus, or an unknown mutation
      which is in linkage disequilibrium with the polymorphism, could be involved in
      the pathophysiology of diabetes. The high heterozygosity may be useful for
      genetic linkage studies of other mutations within and near the IPF1 gene.

PMID- 9628282
TI  - Despite similar rates of alanine release, fasting and diabetes affect de novo
      alanine synthesis differently.

PMID- 9628283
TI  - Hyperexcitability to sulphonylurea in MODY3.

PMID- 9628284
TI  - In search of the keys to the neonatal pulmonary vascular bed.

PMID- 9628285
TI  - Outcome of very low birthweight infants in a sub-Arctic population.

PMID- 9628286
TI  - Body fatness and serum lipids of 11-year-old Chinese children.
AB  - It has been suggested that distribution of body fat has a stronger bearing on
      health risk than total body fat. Magnetic resonance imaging (MRI) was used to
      examine the distribution of fat and correlated with body fat assessed by the
      usual clinical methods-weight, weight-for-height, body mass index (BMI), triceps
      and subscapular skinfold thickness in 11-y-old Chinese children. Lipid profiles
      were used as indicators for coronary risk. Eighty-eight subjects had body fat
      distribution estimated by MRI, while 49 had serum lipids measured. Anthropometric
      parameters correlated significantly with total fat at the umbilical level
      measured by MRI (weight: r = 0.90 in boys, 0.75 in girls; BMI: r = 0.94 in boys,
      0.87 in girls; percent median weight-for-height: r = 0.90 in boys, 0.79 in girls,
      triceps skinfold thickness: r = 0.89 in boys, 0.90 in girls; subscapular skinfold
      thickness: r = 0.93 in boys, 0.88 in girls). Obese subjects had proportionally
      less visceral fat than subcutaneous fat at umbilical level. Using stepwise
      multiple regression, predictive factors for high-density lipoprotein cholesterol
      were BMI in boys and breast-staging in girls. For triglycerides, it was genital
      staging in boys and for total cholesterol, it was breast-staging in girls.
      Visceral fat was not a significant determinant of serum lipids.

PMID- 9628287
TI  - Low immunoglobulin G3 levels in wheezy children.
AB  - This study aimed to investigate the prevalence of IgG subclass deficiency in
      wheezy children aged <3 y. Serum levels of IgA, IgE and IgG subclasses were
      measured in 310 children with recurrent wheezing and in 100 healthy controls.
      IgG3 levels were below the normal lower limit in 123 (39.6%) patients. This
      finding may reflect delayed maturation of the immune system, predisposing young
      children <3 y of age to wheezing.

PMID- 9628288
TI  - The coexistence of thyroid autoimmunity in children and adolescents with various
      allergic diseases.
AB  - The aim of our study was to investigate the coexistence of thyroid autoimmunity
      and allergic diseases. The prevalence of thyroid autoantibodies was studied in
      sera from 140 children with different kinds of allergic diseases, 370 11-13-y-old
      schoolchildren without allergic diseases serving as controls. The prevalence of
      thyroid peroxidase autoantibodies was found to be higher among the patients than
      in the control group, 11.4% vs 5.4% (p < 0.05). Ultrasound investigation
      identified autoimmune thyroiditis in 4.3% (6/140) of the series, which was later
      confirmed with fine needle aspiration in all six cases, four of which were
      unknown prior to the study. Our findings may be useful to alert clinicians that
      thyroid diseases may be superimposed on allergic children.

PMID- 9628289
TI  - Preoperative bacterial colonization of the upper airways does not predict
      postoperative airway infection in children.
AB  - The aim of this prospective non-interventional investigation was to study whether
      preoperative colonization of nasopharynx with potentially pathogenic airway
      bacteria carried an increased risk for the development of early postoperative
      bacterial airway infections after heart surgery in preschool children. Of the 91
      patients studied, 62 (68%) were colonized preoperatively in the nasopharynx with
      Moraxella catarrhalis, Streptococcus pneumoniae, Haemophilus influenzae and/or
      Staphylococcus aureus. Nine children developed postoperative airway infections
      (four pneumonia, three bacterial bronchitis and two acute otitis media).
      Preoperative colonization was not significantly associated with increased risk
      for postoperative airway infection: 6/62 (10%) in colonized vs 3/29 (10%) in non
      colonized children. Preoperative nasopharynx cultures in asymptomatic children
      should be avoided since it is unpleasant for the child, is not cost-effective,
      and may lead to unnecessary antibiotic treatment.

PMID- 9628290
TI  - Body mass index development during the first 6 months of life in infants born to
      human immunodeficiency virus-seropositive mothers.
AB  - The development of body mass index (BMI) was measured during the first 6 months
      of life in three groups of infants [human immunodeficiency virus (HIV) 
      uninfected, n = 92; later symptomatic HIV-infected, n = 18; early symptomatic HIV
      infected, n = 9] born to HIV-positive mothers and compared with a reference group
      (n = 65) born to healthy mothers. A trend towards lower values in the two groups
      of HIV-infected infants was already evident at birth. Among the four groups, HIV
      uninfected infants showed the highest BMI values while the early-infected infants
      showed the lowest BMI values at all measurements. The later-infected group had a
      value close to the reference at 1 month, and then increased at slower rates than
      the uninfected and the reference groups. Infants born to HIV-positive mothers may
      have higher energy and nutrient requirements after birth, either to sustain an
      increased BMI development (when uninfected) or to meet catabolic mechanisms (when
      infected).

PMID- 9628291
TI  - Benign intracranial hypertension and recombinant growth hormone therapy in
      Australia and New Zealand.
AB  - Benign intracranial hypertension (BIH) is reported in three children from
      Australia and one from New Zealand, who were being treated with recombinant human
      growth hormone (rhGH). Three males and one female, aged between 10.5 and 14.2 y,
      developed intracranial hypertension within 2 weeks to 3 months of starting
      treatment. A national database, OZGROW, has been prospectively collecting data on
      all 3332 children treated with rhGH in Australia and New Zealand from January
      1986 to 1996. The incidence of BIH in children treated with growth hormone (GH)
      is small, 1.2 per 1000 cases overall, but appears to be greater with biochemical
      GHD (<10 IU ml(-1)), i.e. 6.5/1000 (3 in 465 cases), relative risk 18.4, 95%
      confidence interval 1.9-176.1, than in all other children on the database. The
      incidence in patients with Turner's syndrome was 2.3/1000 (1 in 428 cases). No
      cases in patients with partial GHD (10-20 IU ml(-1)) or chronic renal failure
      were identified. Possible causative mechanisms are discussed. The authors'
      practice is now to start GH replacement at less than the usual recommended dose
      of 14 IU m(-2) week(-1) in those children considered to be at high risk of
      developing BIH. Ophthalmological evaluation is recommended for children before
      and during the first few months following commencement of rhGH therapy and is
      mandatory in the event of peripheral or facial oedema, persistent headaches,
      vomiting or visual symptoms. The absence of papilloedema does not exclude the
      diagnosis.

PMID- 9628292
TI  - Multicentre survey on compliance with growth hormone therapy: what can be
      improved?
AB  - A survey was undertaken to evaluate compliance in Spanish patients receiving
      growth hormone treatment. The 28-item structured questionnaire was designed to
      collect data on compliance, treatment schedule, device used and instruction
      received. In total, 473 questionnaires were completed in 17 paediatric endocrine
      units. Compliance was divided into four categories based on percentage of doses
      omitted, classified as excellent if 0%, good <5%, fair 5-10% and poor >10%. The
      level of compliance was excellent in 74.0%, good in 20.1%, fair in 3.4% and poor
      in 2.5%. Compliance was better in those who injected themselves (p < 0.01), were
      trained by hospital staff (p < 0.01) and used automatic pens (p < 0.05). Patients
      using conventional syringes were less likely to comply (p < 0.05). More
      information on growth hormone treatment was requested by 57.6% of patients. The
      results indicate that the specialist nurse should spend sufficient time with the
      patients and relatives to ensure a higher compliance rate.

PMID- 9628293
TI  - Infantile hydrocephalus: declining prevalence in preterm infants.
AB  - The prevalence and aetiological panorama of infantile hydrocephalus in western
      Sweden have been followed since the late 1960s. A significant increase in the
      live birth prevalence of very preterm infants with infantile hydrocephalus was
      found, from 6.99 per 1000 in the birth year period 1973-78 to 25.37 in 1983-86,
      and owing to an increased survival of very preterm infants with a high risk of
      hydrocephalus, secondary to an intraventricular haemorrhage occurring in the
      perinatal period. In the present study covering the birth years 1991-94, a
      declining prevalence to 13.69 per 1000 very preterm infants was found. In
      moderately preterm and term groups, mostly with prenatal aetiologies, the
      prevalence was unchanged. Outcome in surviving children with infantile
      hydrocephalus remained essentially the same as in previous studies, indicating
      that the underlying aetiology is the most decisive factor with respect to ensuing
      neuroimpairments.

PMID- 9628294
TI  - A review of cystic fibrosis children born to single mothers.
AB  - The purpose of this study was to examine the relationship between single parents
      and the health of their children with cystic fibrosis. Seventy-five children aged
      between 0.8 and 6.0 y were identified from our patient register; 20 of these
      children came from single parent families. Socioeconomic profiles were collated
      for each family. Retrospective medical data including, gene mutation analysis,
      were recorded from the hospital notes of all 75 patients. Maternal health was
      assessed by means of the General Health Questionnaire (28-item version). The
      results show that maternal age of < or = 19 y and lone parenthood were associated
      with higher morbidity in CF patients <6 y of age. Predicted values of the
      Shwachman score being lower by 4.1 and 4.3 points, respectively. A declining
      Shwachman score of 1.1 points/y was associated with increasing patient's age. In
      addition, analysis showed that the CF children of teenage mothers were 16 times
      more likely to have admission rates of > or = 1/y. Single mothers experienced
      more stress-related symptoms than those from the married group. We concluded that
      the young CF children of single or teenage mothers have a significantly worse
      clinical progress and consequently have a higher demand for hospital services.
      Clearly this population requires extra clinical vigilance and social support.

PMID- 9628295
TI  - The effects of endurance training on selected coronary risk factors in children.
AB  - The effects of regular aerobic exercise on blood concentrations on high-density
      lipoprotein cholesterol and prostacyclin were studied in 18 healthy sedentary
      boys who exercised on a bicycle ergometer for 1 h, four times per week, for 2
      months at 75% of their physical working capacity. The results were compared with
      those of 10 control boys who did not participate in any specific program. The
      exercise group revealed a significantly higher mean high-density lipoprotein
      cholesterol and 6-keto-PGF1a concentration at the end of the training program (p
      < 0.005 and p < 0.001, respectively). These results suggest that regular aerobic
      exercise has beneficial effects upon the high-density lipoprotein cholesterol and
      6-keto-PGF1a in healthy young boys and may be beneficial in the long term, by
      preventing atherosclerosis of coronary artery disease in adulthood.

PMID- 9628296
TI  - Long-term psychological outcome of children after surgery for transposition of
      the great arteries.
AB  - To assess the psychological consequences of a single congenital heart defect, we
      tested intellectual function, self-perception, "body image", child psychiatric
      symptoms and the family climate in 21 boys and 10 girls, at a mean age of 13.2 y,
      on average 11.5 y after surgery for transposition of the great arteries. Where
      applicable, test norms were used for comparison. WISC-R IQ tended to be slightly
      lower than that of the general population. Self-perception, as reflected on the
      "I think I am" test, was normal. "Body image" as measured by the "Draw-a-man"
      test was poor in the boys, but did not show a relationship with any other test
      tapping mental health. Six children (19%) had clinically significant child
      psychiatric symptoms, which is slightly more than expected, and were
      overrepresented in patients with poorer cardiac function. Five of these
      represented "internalizing" disorders. The patients' families scored higher than
      expected on the family climate "chaos" subscale, which has been demonstrated to
      be associated with the development of psychiatric symptoms. Overall, however, the
      children and their families were regarded as socially and psychologically well
      functioning.

PMID- 9628297
TI  - Randomized trial examining cerebral haemodynamics following artificial or animal
      surfactant.
AB  - To determine the effects of animal and artificial surfactants on cerebral
      haemodynamics, 20 premature babies receiving mechanical ventilation were
      randomized to receive Curosurf or Exosurf surfactant. Anterior cerebral artery
      blood flow velocity (CABFV) was measured using Doppler ultrasound before and up
      to 2 h after treatment. Following animal surfactant there was a rapid reduction
      in CABFV (median -36%, range -43% to +8%, p < 0.01), whereas artificial
      surfactant resulted in a slower rise which was less marked (median +20%, range 
      7% to +62%, p < 0.05). There were no significant changes in blood pressure. Two
      hours after administration, the oxygenation index (OI) improved significantly
      only in babies receiving animal surfactant. In this group there was a significant
      association between the change in CABFV at 1 min and the change in OI at 2h (r =
      0.66, p < 0.05). Animal surfactant produces rapid improvements in ventilation
      which are associated with marked alterations in cerebral haemodynamics.

PMID- 9628298
TI  - Changes in skin blood flow over the foot with warming of the contralateral heel.
AB  - Vasospasm in one leg is a common complication of umbilical artery catheterization
      in preterm infants. It is a common practice to wrap the contralateral leg in a
      warm washcloth. The rationale for this intervention is to induce reflex
      vasodilatation of the affected extremity, thereby avoiding the necessity to
      remove or replace the catheter. This study tested the hypothesis that heating the
      contralateral extremity in preterm infants would increase peripheral blood flow
      to the contralateral foot. Ten stable preterm infants who had had no umbilical
      catheter inserted for at least 2 weeks were studied. Skin perfusion was measured
      using the laser Doppler method in the distal leg after heating of the opposite
      foot to 40.5 degrees C. Blood flow to the skin of the contralateral foot was
      measured before and after warming the ipsilateral one. The skin blood flow
      measured with and without heat application to the contralateral foot was not
      significantly different. Direct heat does not induce contralateral reflex
      vasodilatation in the foot of preterm infants.

PMID- 9628299
TI  - Doppler echocardiographic assessment of pulmonary blood flow in healthy newborns.
AB  - The aim of this study was to determine interobserver variation in Doppler
      assessment of mean left pulmonary arterial flow velocity, and its normal values
      during the first 24h of life. The interobserver variation was determined by a
      Bland and Altman analysis of the values of mean velocity measured in 21 newborns
      by 2 observers. Then, normal values of mean velocity were measured in 15 newborns
      at 5, 10 and 15 min of life in the delivery room, and in 14 other newborns at 1,
      2, 6, 12 and 24h of life in the nursery unit. The interobserver variation was
      found to be acceptable. Mean velocity had a few variations within the first 24 h,
      but remained consistently above 20 cm s(-1). In conclusion, mean velocity values
      below 20 cm(-1) suggest low pulmonary blood flow.

PMID- 9628301
TI  - Local application of honey for treatment of neonatal postoperative wound
      infection.
AB  - Honey has been described in ancient and modern medicine as being effective in the
      healing of various infected wounds. In this report we present our experience in
      nine infants with large, open, infected wounds that failed to heal with
      conventional treatment. Conventional treatment was defined as having failed if
      after > or = 14 d of intravenous antibiotic and cleaning the wound with
      chlorhexidine 0.05% W/V in aqueous solution and fusidic acid ointment the wound
      was still open, oozing pus, and swab cultures were positive. All infants showed
      marked clinical improvement after 5 d of treatment with topical application of 5
      10 ml of fresh unprocessed honey twice daily. The wounds were closed, clean and
      sterile in all infants after 21 d of honey application. There were no adverse
      reactions to the treatment. We conclude that honey is useful in the treatment of
      post-surgical wounds that are infected and do not respond to conventional
      systemic and local antibiotic treatment.

PMID- 9628300
TI  - Endothelin-1, atrial natriuretic peptide and pathophysiology of pulmonary
      hypertension in porcine meconium aspiration.
AB  - To evaluate the role of endothelin-1 (ET-1) and atrial natriuretic peptide (ANP)
      in the development of meconium aspiration-induced pulmonary hypertension, plasma
      ET-1 and ANP levels were measured serially for 6h after meconium instillation in
      juvenile pigs. Eleven 10-week-old, anaesthetized and catheterized pigs received
      intratracheally a bolus of 3 ml kg(-1) 20% human meconium, and five of them were
      premedicated with 30 mg kg(-1) methylprednisolone i.v. Another six pigs served as
      controls and were given 3 ml kg(-1) sterile saline intratracheally. Meconium
      instillation resulted in an increase in plasma ET-1 levels with a significant
      correlation to the simultaneously increasing PVR (r = 0.72). Methylprednisolone
      had no effect on the early (0-1 h) ET-1 increase, but prevented significantly the
      second phase (1-6 h) rise with a concomitant attenuation of the progressive
      pulmonary hypertension. ANP concentrations were higher in the meconium than in
      the control group throughout the study and further increased after steroid
      treatment with a good correlation to ET-1 (r = 0.86). Thus, the postinjury rise
      in circulating vasoactive peptides, together with the pulmonary hypertensive
      response, and modulation of the peptide balance and pressor reaction by steroids,
      suggest a contributory role for ET-1 and ANP in the development of pulmonary
      hypertension after meconium aspiration.

PMID- 9628302
TI  - Impact of season and discharge weight on complications and growth of Kangaroo
      Mother Care treated low birthweight infants in Mozambique.
AB  - This study aimed to determine the impact of season and weight at discharge on
      growth rate and complications in low birthweight infants treated with Kangaroo
      Mother Care (KMC) in Maputo, Mozambique. The study population included 246
      infants of birthweight < 2000 g. Follow-up until 2400 g was obtained in 64%.
      There were no seasonal differences in weight gain and the risk of complications
      of infants treated with KMC in hospital. During the cold season after discharge,
      the risk of serious complications, including death, was higher (risk ratio 1.96;
      p = 0.02) and more readmissions occurred (risk ratio 2.77; p = 0.04). We
      postulate that after discharge mothers are unable to comply with the kangaroo
      position at all hours of the day and that exposure to low ambient temperatures
      may explain the more frequent occurrence of complications in the cold season. The
      weight at discharge did not affect complications or growth rate. We conclude that
      the current policy to discharge infants when having gained weight on 3
      consecutive days, regardless of the actual weight, or whether the weight at birth
      has been regained, is adequate. In the cold season particularly, more efforts may
      be needed to ensure compliance with kangaroo position after discharge and to
      educate mothers on early signs of complications such as bronchopneumonia to
      encourage timely care seeking. With this method, low birthweight infants can grow
      adequately.

PMID- 9628303
TI  - Recommendations for the implementation of Kangaroo Mother Care for low
      birthweight infants. International Network on Kangaroo Mother Care.
AB  - Good quality care of low birthweight infants could reduce neonatal mortality in
      low-income countries, but the technologies used in rich countries are
      inappropriate. Kangaroo Mother Care does not need expensive and sophisticated
      equipment, and for its simplicity it can be applied almost everywhere, including
      peripheral maternity units of very low-income countries. Kangaroo Mother Care
      (KMC) can also contribute to the humanization of neonatal care and to better
      bonding between mother and baby in both poor and rich countries. A group of
      health professionals with experience in KMC met in a workshop to discuss its
      effectiveness, safety, applicability and acceptability in different settings:
      from first and second level maternity units in settings with very limited
      resources, to second and third level units in settings with limited resources, to
      second and third level maternity and neonatal care units in settings with ample
      resources and infant mortality rates <15/1000. The paper summarizes the
      recommendations of this group of health professionals for the implementation of
      KMC in these various settings, together with suggested research priorities.

PMID- 9628304
TI  - Very low birthweight infants: outcome in a sub-Arctic population.
AB  - OBJECTIVE: To evaluate the outcome for very low birthweight (VLBW) infants in
      northern Norway. SUBJECTS AND METHODS: All live born infants (n = 536) with
      birthweight < or = 1500 g born during 1978-89 to women residing in the northern
      health region of Norway were studied retrospectively. Data were from the Medical
      Birth Registry (MBR), hospital records and from follow-up recordings to 4 y of
      age at maternal and child health centres. Stillborn infants (n = 269) with
      birthweight < or = 1500 g during the same period were also registered. RESULTS:
      The annual incidence of live born VLBW infants (7.1/1000 live births) did not
      change, but the proportion of infants born alive before 26 weeks' gestation
      increased and the stillborn part decreased significantly. The Caesarean section
      (CS) rate, antenatal transfer and the use of a neonatal transport team increased
      significantly. Four hundred and seventy-five infants (89%) were considered viable
      at birth, 347 (65%) survived to 1 y and 343 (64%) to 4 y. The likelihood of
      survival was independently related to female gender. The trend for survival to 4
      y of age did not increase significantly. Thirty children suffered from cerebral
      palsy (8.7% of survivors, 5.6% of live births) and the cerebral palsy rate for
      infants with birthweight 751-1000 g decreased. The proportion of survivors
      considered to be normal or mild disabled increased and the part suffering from
      moderate or severe disability decreased significantly. CONCLUSIONS: In spite of
      long distances and unfavourable climatic conditions VLBW infants can be
      adequately cared for in this sparsely populated region of Norway.

PMID- 9628305
TI  - Spinal cord compression--do we miss it?
AB  - Four children with spinal cord compression due to malignant tumours are
      presented. The severity of the condition was not initially recognized by parents,
      or the nature of the likely cause by the initial physicians. Lower limb
      asymmetrical weakness, clear-cut sensory levels, and marked pain indicate need
      for urgent imaging and exclusion of a space occupying lesion. In 1997 diagnosis
      of Guillain-Barre syndrome should not be made without careful prior spinal
      imaging.

PMID- 9628306
TI  - Combination of ABO blood group incompatibility and glucose-6-phosphate
      dehydrogenase deficiency: effect on hemolysis and neonatal hyperbilirubinemia.
AB  - The incidence (%) of hyperbilirubinemia (serum bilirubin > or = 257 micromol/l)
      was similar in neonates with a combination of ABO incompatibility and glucose-6
      phosphate dehydrogenase (G-6-PD) deficiency (45%), with ABO incompatibility (54%)
      or G-6-PD deficiency (37%), alone (ns). Carboxyhemoglobin values, corrected for
      inspired CO, were similarly elevated in all three groups (0.87 +/- 0.32%, 0.82 +/
      0.29%, 0.76 +/- 0.18%, respectively, ns), but correlated with bilirubin only in
      those with ABO incompatibility alone. ABO-incompatible/G-6-PD-deficient neonates,
      compared with those with either condition alone, are not at increased risk for
      hemolysis or hyperbilirubinemia.

PMID- 9628307
TI  - Routine vaccination and vaccine-preventable infections in children born to human
      immunodeficiency virus-infected mothers. European Collaborative Study.
AB  - Information on vaccinations and vaccine-preventable infections collected in a
      prospective study of children born to human immunodeficiency virus (HIV)-infected
      mothers was analysed for reports of adverse reactions and to estimate the
      clinical efficacy of vaccines. No vaccinated, HIV-infected child developed
      measles (56 child-years' follow-up), mumps (33), rubella (33) or pertussis (239),
      and only one adverse reaction - to Bacillus Calmette-Guerin (BCG) - was reported.
      These findings provide limited evidence of the safety and efficacy of routine
      vaccination of HIV-infected children.

PMID- 9628308
TI  - Relationship of apolipoprotein E phenotypes to serum lipid and lipoprotein levels
      in Japanese schoolchildren.
AB  - The distribution of apolipoprotein (apo) E phenotypes was investigated in
      Japanese schoolchildren and an attempt was made to determine whether the apoE
      phenotypes influence the serum levels of lipid and lipoprotein. The subjects were
      289 children from a junior high school (145 M, 144 F, aged 12-13 y). The E3/3
      phenotype was demonstrated in 69.9%, E4/3 in 18.7%, E2/3 in 9.0%, E4/2 in 1.4%,
      E4/4 in 0.7% and E5/4 in 0.3%. E2/2 was not detected. Serum levels of total
      cholesterol and low-density lipoprotein-cholesterol were progressively lower in
      the phenotypes E4/3, E3/3 and E2/3. The serum level of high-density lipoprotein
      cholesterol showed a progressive increase in the same order. In conclusion,
      Japanese schoolchildren with E4/3 already had an atherogenic serum lipid profile.

PMID- 9628309
TI  - Dietary treatment for regurgitation--recommendations from a working party.
AB  - Regurgitation is a common manifestation in infants below the age of 1 y, and is a
      frequent reason for counselling of general practitioners and paediatricians.
      Current recommended therapeutic management starts with parental reassurance and
      dietary measures, followed by prokinetics. In this paper, the efficacy, safety
      and nutritional implications of the dietary treatment of regurgitation are
      evaluated. Industrially prepared thickened feeds may contain cereals of fibres;
      some have a low lipid content and are casein-predominant. Milk-thickened agents
      can also be added to regular infant feeding. Formulae claimed as "anti
      regurgitation formulae", or positioned as such, should be considered as medical
      foods or therapeutic diets, and only be available on medical prescription. It is
      proposed to limit the "anti-regurgitation" (AR) label to those diets which have
      been proven clinically effective on regurgitation and which are nutritionally
      safe.

PMID- 9628310
TI  - Enterovirus-associated haemophagocytic syndrome in a neonate.
AB  - A 3-d-old neonate presented with fever, hepatosplenomegaly, coagulopathy,
      thrombopenia and anaemia. Secondary haemophagocytic lymphohistiocytosis was
      suspected, as persistent cytopenias were associated with hypofibrinogenaemia,
      haemophagocytosis in bone marrow and decreased NK cell. There was no positive
      family lymphohistiocytosis history or parental consanguinity. Bacterial
      investigation proved negative. The diagnosis of enterovirus maternofoetal
      infection was carried out. The infant's condition improved with symptomatic
      therapy from day 7. Follow up at 1 y was normal without relapse. This is the
      first report of a neonatal enteroviral infection that was responsible for
      excessive macrophage activation.

PMID- 9628311
TI  - Recurrent Pseudomonas bronchopneumonia and other symptoms as in cystic fibrosis
      in a child with type I pseudohypoaldosteronism.
AB  - We report a child with multiple target organ pseudohypoaldosteronism type 1 with
      frequent recurrent pulmonary infections caused by Pseudomonas aeruginosa and
      Pasteurella multocida and high levels of chloride in sweat, urine and nasal
      secretion. Repetitive faecal chymotrypsin samples have all shown pathological
      values in spite of no other sign of exocrine pancreas dysfunction. The
      similarities with cystic fibrosis and the importance of the salt content in
      bronchial fluid are discussed.

PMID- 9628313
TI  - Toys within chocolate eggs--an ingestion hazard.

PMID- 9628312
TI  - Multiple anomalies, hypokalaemic paralysis and partial symptomatic relief by
      terbutaline.
AB  - In this paper a follow-up is presented of a case report initially described by
      Andersen in 1971. The patient presented with a syndrome including elements of
      familial periodic paralysis with hypokalaemia, long QT syndrome, ventricular
      ectopy, myopathy with fibre-type disproportion and dysmorphic features resembling
      Treacher Collins' syndrome. The main symptom was hypokalaemic paralysis. The
      episodes were accompanied by a lowered intracellular potassium content and an
      increase in intracellular sodium. Treatment with terbutaline, a Na/K-ATPase
      stimulating drug, resulted in attack-free periods of approximately 9 months,
      after which the attacks reoccurred. The patient suffered severe attacks whenever
      treatment with terbutaline was stopped. The patient experienced two attacks of
      respiratory arrest, the second being fatal.

PMID- 9628314
TI  - Accurate means of measuring breastfeeding prevalence.

PMID- 9628315
TI  - No negative influence of EMLA application prior to BCG vaccination.

PMID- 9628316
TI  - Identification and characterization of a novel kind of nuclear protein occurring
      free in the nucleoplasm and in ribonucleoprotein structures of the "speckle"
      type.
AB  - We have identified, by cDNA cloning and immunodetection, a novel type of
      constitutive nuclear protein which occurs in diverse vertebrate species, from
      Xenopus laevis to man, in the form of two different gene products (79.1 kDa and
      82.1 kDa in Xenopus, 81.6 kDa and 84.6 kDa in man), remarkably differing in pI
      (5.4-7.2). This type of protein is characterized by a carboxyterminal domain
      extremely rich in hydroxyamino acid residues, notably Ser (S), and tetrapeptide
      repeats of the type XSRS, and hence is termed "domain rich in serines" (DRS)
      protein. It has been immunolocalized exclusively in the cell nucleus such as in
      blood cell smears, cultured cells of very different origins and tissue sections,
      and has also been identified in Xenopus oocyte nuclei, both in sections and by
      biochemical methods in manually isolated nuclei. In many cell types the protein
      appears in two different physical states: (i) nuclear granules, identified as
      ribonucleoprotein (RNP) structures of the "speckle" category by colocalization
      and cofractionation with certain splicing factors and Sm-proteins, and (ii) in
      molecules diffusible throughout the nucleoplasm. During mitosis and also in
      meiosis (Xenopus eggs) the protein is transiently dispersed throughout the
      cytoplasm but rapidly reaccumulates into the reforming daughter-nuclei. In
      agreement with this, biochemical experiments have shown that during meiosis
      (eggs) the protein is recovered in a approximately 11-13S complex of the fraction
      of soluble cell components. We discuss general constitutive nuclear functions of
      this apparently ubiquitous and evolutionarily conserved protein.

PMID- 9628317
TI  - Epithelial and fibroblastoid cells contain numerous cell-type specific putative
      microtubule-regulating proteins, among which are ezrin and fodrin.
AB  - Upon cell junction formation, the microtubules of polarizing epithelial cells
      become reorganized by unknown signaling mechanisms and regulating proteins.
      Microtubule-associated (MAPs) and other types of proteins are likely to be
      involved in this process, but most of these are unknown. Such proteins are called
      here collectively microtubule-regulating proteins (MRPs). As a first step towards
      their characterization, we used co-sedimentation of cytosolic proteins of MDCK
      cells and A72, a dog fibroblastoid line, with an excess of taxol-stabilized MTs,
      to obtain a cell fraction enriched in putative MRPs ("MRPs"). Additional tests
      have led to the inventory of around 40 "MRPs" among the 80 proteins present in
      the microtubule pellet. We also found that "MRPs" are recovered in higher amounts
      from MDCK cytosol, and that half of these are cell-type specific. These results
      corroborate data from yeast cells and insect eggs, and show that in mammalian
      somatic cells too, a large number of proteins seems to be involved in microtubule
      regulation, and that different cell types use a specific set of MRPs. "MRPs"
      found in both cell types are the intermediate chain of cytoplasmic dynein, Arp1,
      the major subunit of the dynactin complex, and CLIP-170. Two MDCK-specific "MRPs"
      were identified as the actin-binding proteins ezrin and alpha-fodrin. These
      results are discussed with regard to a possible involvement of ezrin and fodrin
      in morphogenetic interactions of microtubules with the membrane cytoskeleton in
      polarizing epithelia upon junction formation.

PMID- 9628318
TI  - The rat mucosal mast cell chymase, RMCP-II, alters epithelial cell monolayer
      permeability in association with altered distribution of the tight junction
      proteins ZO-1 and occludin.
AB  - Mucosal mast cells undergo hyperplasia in a variety of inflammatory bowel
      diseases including nematode infection in man and animals. The intra-epithelial
      localization of these cells make their soluble mediators prime candidates for
      modulators of epithelial function. In particular previous in vivo and ex vivo
      studies have established a link between the release of the highly soluble mast
      cell granule chymases and increased mucosal permeability. The hypothesis that the
      rat mast cell protease, RMCP-II, directly increases permeability to
      macromolecules via the paracellular route is tested in this study. Monolayers of
      epithelial cells (Madin-Darby canine kidney cell line) were exposed to varying
      concentrations of RMCP-II in vitro, in the absence of other cell types or
      mediators, and the effect on permeability and tight junction associated proteins
      was investigated. Basolateral, but not apical, exposure of polarized MDCK
      monolayers on porous supports to RMCP-II led to concentration- (> 100 microg/ml)
      and time-dependent increases in electrical conductance and permeability to
      mannitol (MW182) and inulin (MW5000), which was accompanied by decreases in the
      immunostaining of the tight junction-associated proteins occludin and ZO-1.
      Furthermore, prolonged exposure to RMCP-II (> 12 hours) resulted in the formation
      of identifiable gaps separating adjacent epithelial cells, in the absence of
      evidence of cytotoxicity. Inhibition of RMCP-II with Soya bean trypsin inhibitor
      completely abrogated the response, demonstrating that proteolysis was required.
      These data provide direct evidence that the rat mast cell chymase RMCP-II can, in
      the absence of other inflammatory mediators, increase epithelial permeability via
      an effect on the paracellular route.

PMID- 9628319
TI  - The transmembrane domain enhances granular targeting of P-selectin.
AB  - P-selectin is an integral membrane glycoprotein that is stored in granules of
      endothelial cells and platelets. The cytoplasmic domain of P-selectin is known to
      contain at least part of the signal that directs the protein to storage granules.
      In order to more fully understand how P-selectin is targeted to the regulated
      secretory pathway, we have expressed chimeric constructs between P- and E
      selectin, a protein which is expressed on the cell surface, in a rat insulinoma
      cell line. Immunofluorescence studies indicated that replacing the cytoplasmic
      domain of E-selectin with that of P-selectin resulted in low-level granular
      expression. In contrast, when both the transmembrane and cytoplasmic domains of E
      selectin were replaced with the analogous domains of P-selectin, the granular
      localization appeared greatly increased. This was confirmed by immunoelectron
      microscopy which demonstrated a three- to fourfold improvement in granular
      targeting, i.e. similar to wild-type P-selectin. The transmembrane domain had to
      be in the context of the P-selectin cytoplasmic domain as this membrane-spanning
      region could not induce granular targeting on its own. These results describe a
      novel function for the transmembrane domain of P-selectin in enhancing the
      efficiency of granular targeting and further implicate protein transmembrane
      domains in intracellular trafficking.

PMID- 9628320
TI  - At reduced temperature, endocytic membrane traffic is blocked in multivesicular
      carrier endosomes in rat cardiac myocytes.
AB  - Temperatures around 20 degrees C are known to block degradation of endocytosed
      material by preventing its transport to lysosomes, accordingly reduced
      temperature has been widely used to define endosomes. Newer studies have revealed
      that the low temperature block is proximal to perinuclear late endosomes, but it
      is not clear whether the block is already in early endosomes, or whether the
      traffic proceeds to multivesicular carrier endosomes which mediate transport from
      early to late compartments. We have now focused on this problem using rat cardiac
      myocytes. First, cell fractionation on Percoll gradients showed that at reduced
      temperatures (22 degrees C and 26 degrees C), with prolonged chase periods,
      endocytosed horseradish peroxidase was able to proceed from early endosomes to
      later compartments but not up to lysosomes. Further, microscopic experiments with
      fluorescent endocytic marker FITC-dextran showed that the marker did not
      accumulate in the perinuclear area, as was the case at 37 degrees C, but stayed
      in peripheral cytoplasm at reduced temperatures, even after 16-h chase. Second,
      electron microscopic pulse labeling showed that, at 22 degrees C, endocytosed
      gold particles (BSA-gold) are transported to compartments not accessible to HRP
      internalised later to early endosomes. Thus, these gold particles had reached a
      later compartment. Morphologically these vesicles were multivesicular bodies of
      0.5-1 microm in diameter. Third, we used fluorescence microscopy to study the
      effect of reduced temperature on transferrin uptake and recycling. At 17 degrees
      C and 22 degrees C, transferrin was internalized normally to peripheral (sorting)
      and perinuclear (recycling) vesicles. If transferrin was first taken up at 37
      degrees C, and the cells were then chased at various temperatures from 37 degrees
      C to 17 degrees C, the recycling was slowed down but not entirely blocked at the
      reduced temperatures. From these results we can conclude that (1) endocytic
      traffic is blocked in multivesicular carrier endosomes at and below 26 degrees C,
      and that (2) reduced temperature slows down transport in the recycling pathway,
      without a complete block.

PMID- 9628321
TI  - Polarized expression of heterologous membrane proteins transfected in a human
      endothelial-derived cell line.
AB  - The generation and maintenance of cell polarity in endothelial cells is poorly
      understood, partly because of a lack of a permanent endothelial in vitro model
      system. Here we evaluated the spontaneously immortalized human endothelial
      derived cell line ECV304 as an in vitro model system for the study of the
      polarized expression of heterologous membrane proteins. Several stable ECV304
      clones were generated by calcium phosphate transfection/G418 selection with cDNAs
      encoding membrane proteins of known cell surface distribution in the epithelial
      Madin Darby canine kidney (MDCK) cell line: influenza hemagglutinin and
      uvomorulin/E-cadherin were used as markers for the apical, respectively lateral
      cell membrane, the human lymphocyte surface marker CD7 served as an example of a
      circumferentially distributed membrane protein. Analysis of the transfected
      ECV304 clones using conventional and confocal immunofluorescence microscopy and
      immunoelectron microscopy revealed the same membrane distribution of the
      heterologous proteins in ECV304 cells as in MDCK cells. This polarized expression
      of heterologous membrane proteins in the endothelial-derived ECV304 cell line
      indicates efficient protein sorting/membrane trafficking mechanisms. The apical,
      lateral and basal cell membrane domains could be distinguished in ECV304 cells by
      confocal immunofluorescence microscopy. The permanent endothelial-derived ECV304
      cell line may be a useful in vitro model system for the study of endothelial cell
      polarity.

PMID- 9628322
TI  - PDGF and TGF-beta induce cell shape changes in invertebrate immunocytes via
      specific cell surface receptors.
AB  - The presence of PDGF receptor-alpha- and -beta- and TGF-beta-receptor (type II)
      like molecules on the plasma membranes of the immunocytes of the mollusc Mytilus
      galloprovincialis was demonstrated by an immunocytochemical procedure.
      Furthermore, the present study provides evidence that PDGF-AB and TGF-beta1
      provoke cell shape changes in immunocytes via interactions with the respective
      receptors and that these extracellular signals are transduced along the
      phosphoinositide signaling pathway.

PMID- 9628323
TI  - Expression of bcl-2 and bax in TGF-beta 1-induced apoptosis of L1210 leukemic
      cells.
AB  - TGF-beta1 is a multifunctional regulatory peptide (25 kDa) inducing growth arrest
      and apoptosis in many normal and neoplastic cells. In the present study, the
      involvement of proapoptotic (bax) and antiapoptotic (bcl-2) genes in the
      molecular mechanism of TGF-beta1-induced apoptosis of L1210 leukemic cells was
      investigated. Bax transcript was measured using the RT-PCR method with GAPDH as a
      "housekeeping gene" control, whereas Bcl-2 protein was determined using flow
      cytometry (FITC-conjugated monoclonal anti-Bcl-2 antibody and FITC-conjugated
      mouse anti-IgG1 antibody as a negative control). Apoptosis was evaluated using
      fluorescence microscopy and flow cytometry after cell staining with DAPI and
      sulforhodamine or propidium iodide and Hoechst 33342. ROS generation was assessed
      by flow cytometry using the oxidation-sensitive fluorescent marker C-DCDHF-DA.
      The response of L1210 leukemic cells to TGF-beta1 was two-directional: 1) partial
      arrest of the cell cycle at G1-S transition, and 2) induction of apoptotic cell
      death. TGF-beta1 increased the number of leukemic cells with typical
      morphological features of apoptosis: cell shrinkage, condensation of chromatin,
      pyknosis and fragmentation of nuclei, followed by secondary necrosis. DNA
      cleavage led to a decrease of the nuclear DNA content and the appearance of a
      hypodiploid peak sub-G1 in the DNA histogram. The extraction of low-molecular
      weight DNA fragments from apoptotic cells showed that TGF-beta1-induced apoptosis
      concerned first of all the cells from G1 phase. Two phases of intracellular ROS
      generation in TGF-beta1-treated cultures were observed: the first (rapid, 60 min
      after TGF-beta1 administration), and the second (slow, occurring between 24 and
      48h of experiment, respectively). The increase of apoptotic cell number in TGF
      beta1-treated cultures (2% FCS/RPMI 1640) was associated with the decrease of
      cell number expressing bcl-2, and with a significant drop of Bcl-2 level in the
      remaining cells after 24 h. The dose-dependent relationship between TGF-beta1
      concentration and Bcl-2 level was nonlinear and described by power series
      regression. The lowest Bcl-2 level was noted at 1 ng/ml of TGF-beta1
      concentration. The increase of Bax mRNA:GAPDH mRNA ratio was observed 3h after
      TGF-beta1 (1 ng/ml) administration to both the maintenance (2% FCS/RPMI) and
      growth promoting (10% FCS/RPMI) medium. Regardless of TGF-beta1 treatment, the
      quantity of Bax transcript was dependent on FCS concentration, being higher in
      the growth promoting medium. The results of this study indicate that bax may
      function as a primary response gene and together with lowered Bcl-2 level may
      determine the induction of apoptotic process in L1210 leukemic cells exposed to
      TGF-beta1.

PMID- 9628324
TI  - Rat yolk sac explants as a system for studying the regulation of endodermal
      genes: down-regulation of the alpha-fetoprotein gene by dexamethasone and phorbol
      ester.
AB  - The visceral yolk sac is a fetal membrane with essential placental functions. It
      is the major site of synthesis of alpha-fetoprotein (AFP), the most abundant
      plasma protein in the fetus. We developed a system of rat yolk sac explants in
      serum-free culture medium to study the regulation of endodermal gene expression
      in yolk sac. The explanted yolk sac tissues retained their double-sided
      morphology for up to 48 hours. The epithelial cells of both layers remained
      tightly joined on a basement membrane as seen by light and electron microscopy.
      This probably accounts for the continued expression of several endodermal cell
      specific markers. The levels of mRNA encoding AFP, vitamin D-binding protein
      (DBP), hepatocyte nuclear factor 1alpha and beta transcription factors did not
      change during the 48-hour culture period. This reflects the stability of the
      differentiation state of the yolk sac endodermal cells. Dexamethasone and phorbol
      ester (TPA) specifically reduced the AFP mRNA level without affecting that of
      DBP. This suggests that these transduction pathways are functional in the yolk
      sac during this period of gestation and could be involved in the physiological
      down-regulation of AFP gene expression before birth. All these results show that
      this serum-free culture of rat yolk sac explants is a valuable system for further
      investigating the action of natural compounds and pharmacological drugs on
      endodermal gene expression during the embryonic and fetal periods.

PMID- 9628325
TI  - Interleukin pattern of Apert fibroblasts in vitro.
AB  - The phenotype of cultured fibroblasts from patients affected by Apert's syndrome,
      a rare connective disorder, differs from that of normal cells in its
      extracellular matrix macromolecule composition (glycosaminoglycans, collagens and
      fibronectin) and is further modulated by treatment with interleukins (ILs). As
      the mechanisms responsible for the changes are unknown, we used our recently
      described model system for Apert periosteal fibroblasts to ascertain whether the
      pattern of ILs they secrete into the medium is comparable to that of normal
      fibroblasts. The results obtained by enzyme-linked immunosorbent assay (ELISA)
      show that the levels of interleukin-1 (IL-1) and interleukin-6 (IL-6) were lower
      in Apert than in normal media, whereas levels of IL-1 receptor antagonist (IL
      1ra), the natural inhibitor of IL-1, were markedly higher. IL-1 specific bio
      activity on thymocyte proliferation was also decreased in Apert supernatants. As
      we provided also evidence that active transforming growth factor beta (TGFbeta1),
      an IL-1 antagonist, was not secreted in greater amount in Apert media with
      respect to normals, the enhancement of IL-1ra appeared critical in down
      regulating IL-1. Northern blot analysis of cytokine mRNA revealed no detectable
      IL-1 or IL-6 gene expression in normal fibroblasts, but high amounts of IL-6 mRNA
      transcripts in Apert cells. As the increased IL-6 gene expression did not
      translate into a parallel increase of secreted IL-6, the control of IL-6
      secretion may be mainly post-transcriptional. Furthermore, the result that a
      treatment of the cultures with IL-1ra was able to induce a decrease of IL-6
      secretion, suggests that the observed decreased secretion of IL-6 may be due to
      the autocrine action of overproduction of IL-1ra. The observed imbalance in the
      production of ILs which we show for the first time suggests ILs may be the
      natural autocrine regulators of ECM production in Apert fibroblasts. We
      hypothesize that in vitro differences previously reported in fibroblast
      phenotypes and several clinical features of Apert's syndrome may correlate with
      different cytokine patterns.

PMID- 9628326
TI  - Heterogeneous carbamoylphosphate synthetase I expression in testicular
      transplants of fetal mouse liver.
AB  - Expression of carbamoylphosphate synthetase I (CPSI; EC 6.3.4.16) was examined
      immunohistochemically in normal development of the mouse liver, and in testicular
      transplants of fetal liver fragments. CPSI started to be expressed in all
      hepatocytes around 15 days of gestation, and became heterogeneous (i.e. absent
      from pericentral hepatocytes) around 2 weeks after birth. Most hepatocytes in
      fetal liver fragments placed for 2 months under the testicular capsule expressed
      this enzyme except for the pericentral ones, most of which were positively
      stained with anti-glutamine synthetase (GS; EC 6.3.1.2) antiserum. This
      distribution resembled that in the adult liver. The steep change in CPSI
      immunostaining in liver lobules suggests that the microenvironment tightly
      connected to the central veins plays an important role in the suppression of CPSI
      expression in the pericentral hepatocytes. Some pericentral hepatocytes were also
      negative for both enzymes. Thus, control mechanisms of CPSI expression may be
      different from those of GS expression in pericentral hepatocytes.

PMID- 9628327
TI  - Enzymatic methylation of DNA--roles and prospects.

PMID- 9628328
TI  - Involvement of DNA methylation in human carcinogenesis.
AB  - It is now generally accepted that the presence of 5-methylcytosine (5mC) in human
      DNA has both a genetic and an epigenetic effect on cellular development,
      differentiation and transformation. First, 5mC is more unstable than its
      unmethylated counterpart cytosine. Hydrolytic deamination of 5mC leads to a G/T
      mismatch and subsequently, if unrepaired, to a C-->T transition mutation. Sites
      of DNA methylation are mutational hotspots in many human tumors. Second, DNA
      methylation of promoter regions is often correlated with the down regulation of
      the corresponding gene. Both of these effects have fundamental consequences for
      basic functions of the cell like cellular differentiation, the development of
      cancer and possibly other diseases, and on the evolutionary process. Recent
      hypotheses also propose a role for methylation in the process of aging. In this
      review we will describe recent findings and hypotheses about the function of 5mC
      in DNA with the focus on its involvement in human carcinogenesis.

PMID- 9628329
TI  - M.TaqI: possible catalysis via cation-pi interactions in N-specific DNA
      methyltransferases.
AB  - The adenine-specific DNA methyltransferase M.TaqI transfers a methyl group from S
      adenosylmethionine to N6 of the adenine residue in the DNA sequence 5'-TCGA-3'.
      In the crystal structure of M.TaqI in complex with S-adenosylmethionine the
      enzyme is folded into two domains: An N-terminal catalytic domain, whose fold is
      conserved among S-adenosyl-methionine dependent methyltransferases, and a DNA
      recognition domain which possesses a unique fold. In the active site, two
      aromatic residues, Tyr 108 and Phe 196, are postulated to bind the flipped-out
      target DNA adenine which becomes methylated. By lowering the energy of the
      positively charged transition state via cationic-pi interactions, these two
      residues probably hold a key role in catalysis.

PMID- 9628330
TI  - DNA demethylation: turning genes on.
AB  - The regulation of eukaryotic gene expression is a complicated process involving
      the interaction of a large number of transacting factors with specific cis
      regulatory elements. DNA methylation plays a role in this scheme by acting in cis
      to modulate protein-DNA interactions. Several lines of evidence indicate that
      methylation serves to silence transcription, mainly through indirect mechanisms
      involving the assembly of repressive nucleoprotein complexes. DNA demethylation
      is mostly an active enzymatic process, controlled by cis regulatory elements
      which provide binding sites for trans demethylation factors. In the immune system
      DNA methylation plays multiple roles, such as regulating both gene expression and
      gene rearrangement

PMID- 9628331
TI  - The estrogen responsive element of the pS2 gene is recognized by a methylation
      sensitive DNA binding protein.
AB  - The human pS2 gene is specifically expressed is a subclass of estrogen receptor
      containing human breast cancer cells. In the MCF7 cell line, its induction by
      estradiol is a primary transcriptional event. The exact location of its estrogen
      responsive element has been determined using a chimeric recombinant transfected
      into HeLa cells and a transient expression assay. In this study we found, using
      electrophoretic mobility shift experiments, that in HeLa cells the estrogen
      responsive element (ERE) of the pS2 gene is recognized by a methylation sensitive
      DNA binding protein (MSDBP) different from the estrogen receptor. Competition
      experiments have shown that the binding of this protein requires at least one CpG
      in the center of the palindromic sequence and that imperfect palindromic
      sequences are also recognized. Although the presence of CpG is necessary, CpG
      rich oligonucleotides, containing consensus sequences for Sp1 or AP2, do not
      interfere with its binding to the pS2 oligonucleotide, indicating that the ERE
      sequence itself participates in the specificity of its binding. This protein
      binds the pS2 sequence with a relatively high affinity (apparent Kd = 10(-10) M)
      and its binding is strongly reduced by the methylation of the cytosines at CpG
      sites. UV cross-linking experiments and peptide mapping indicate that this
      protein has an apparent molecular weight of 46 kDa and is present in several cell
      lines, including non-human cell lines. Taken together, these data suggest that
      this protein might have a potential role in regulating gene activity or in
      chromatin structure of some genes possessing an ERE.

PMID- 9628332
TI  - Analysis of methylation patterns in the regulatory region of the latent Epstein
      Barr virus promoter BCR2 by automated fluorescent genomic sequencing.
AB  - We analyzed the methylation patterns of CpG dinucleotides in the regulatory
      region of the latent Epstein-Barrvirus (EBV) promoter BCR2 (also called C
      promoter, Cp) using automated fluorescent genomic sequencing after bisulfite
      induced modification of DNA. BCR2 is one of the alternative promoters for
      transcripts encoding the growth-transformation-associated nuclear antigens EBNA 1
      6 which are expressed in a host cell phenotype dependent manner. Well
      characterized clones isolated from the Burkitt's lymphoma (BL) line Mutu
      differing from each other as to their phenotype and EBV latent gene expression
      were used in the present study. We found that in Mutu BL III clone 99 which is
      actively using the BCR2 promoter the regulatory sequences are unmethylated with
      two exceptions (position 10702 and 10799). In contrast, there are 15 methylated
      cytosines in the same region in Mutu BL I clone 216 where the BCR2 promoter is
      silent. Cytosines which are potential targets of DNA methyltransferase in the
      immediate vicinity or within the attachment sites of cellular C promoter binding
      factors CBF1 and CBF2 remained hypomethylated in Mutu BL I clone 216. This
      suggests a role for a hypermethylated region (nucleotides 10666 -10865, -639 to 
      440 bases upstream from the beginning of the TATA box at position 11305) in
      silencing of the BCR2 promoter in these cells.

PMID- 9628333
TI  - Chlorella viruses encode multiple DNA methyltransferases.
AB  - The >320 kb dsDNA genomes of 16 viruses which infect Chlorella strain NC64A and 5
      viruses infecting Chlorella strain Pbi were tested for their
      sensitivity/resistance to more than 80 DNA restriction endonucleases. From the
      known methylation sensitivities of these enzymes to site-specific 5
      methylcytosine and N6-methyladenine DNA modifications, we deduce that the 16
      NC64A viruses encode at least 13 different sequence-specific DNA
      methyltransferases and the 5 Pbi viruses encode at least 7 sequence-specific DNA
      methyltransferases. Each DNA methyltransferase has a 2 to 4 base pair DNA
      recognition sequence. Some individual viruses encode as many as ten different DNA
      methyltransferases, making these chlorella virus genomes among the most
      concentrated sources of DNA methyltransferase genes known.

PMID- 9628334
TI  - Selfish restriction modification genes: resistance of a resident R/M plasmid to
      displacement by an incompatible plasmid mediated by host killing.
AB  - Previous work from this laboratory demonstrated that plasmids carrying a type II
      restriction-modification gene complex are not easily lost from their bacterial
      host because plasmid-free segregant cells are killed through chromosome cleavage.
      Here, we have followed the course of events that takes place when an Escherichia
      coli rec BC sbcA strain carrying a plasmid coding for the PaeR7I restriction
      modification (R/M) gene complex is transformed by a plasmid with an identical
      origin of replication. The number of transformants that appeared was far fewer
      than with the restriction-minus (r-) control. Most of the transformants were very
      small. After prolonged incubation, the number and the size of the colonies
      increased, but this increase never attained the level of the r- control. Most of
      the transformed colonies retained the drug-resistance of the resident, r+ m+
      plasmid. These results indicate that post-segregational host killing occurs when
      a plasmid bearing an R/M gene complex is displaced by an incompatible plasmid.
      Such cell killing eliminates the competitor plasmid along with the host and,
      thus, would allow persistence of the R/M plasmid in the neighboring, clonal host
      cells in nature. This phenomenon is reminiscent of mammalian apoptosis and other
      forms of altruistic cell death strategy against infection. This type of
      resistance to displacement was also studied in a wild type Escherichia coli
      strain that was normal for homologous recombination (rec+). A number of
      differences between the recBC sbcA strain and the rec+ strain were observed and
      these will be discussed.

PMID- 9628335
TI  - Sequence comparison of the EcoHK31I and EaeI restriction-modification systems
      suggests an intergenic transfer of genetic material.
AB  - The genes coding for the EcoHK31I and EaeI restriction-modification (R-M) systems
      from Escherichia coli strain HK31 and Enterobacter aerogenes, respectively, have
      been cloned and sequenced. Both ENases recognize and cleave Y/GGCCR leaving 4
      nucleotide 5'-protruding ends, while the MTases modify the internal cytosine. The
      systems were isolated on a 2.3kb AseI fragment for EcoHK31I, and a 4.6 kb HindIII
      fragment for EaeI. The R and M genes of both systems converge and overlap by 14
      nucleotides. Previously, we found that M.EcoHK31I consisted of two subunits,
      (alpha and beta), with the beta subunit being translated from an alternative open
      reading frame within the gene encoding the alpha subunit. Sequence comparison
      between the EcoHK31I and EaeI systems reveals striking similarity. The eaeIM gene
      also encodes alpha and beta polypeptides of 309 and 176 amino acids which share
      96% and 97% identity, respectively, with those of ecoHK31IM. ecoHK31IR and eaeIR
      encode proteins of 318 and 315 aa, respectively, which share 92% identity but are
      otherwise unique in the GenBank database. The EaeI and the EcoHK31I R-M systems
      were found to be flanked by genes coding for integrases. It is possible that
      these integrases have facilitated the transfer of this system among different
      bacterial species.

PMID- 9628336
TI  - Characterization of LlaCI, a new restriction-modification system from Lactococcus
      lactis subsp. cremoris W15.
AB  - The genes encoding the restriction-modification (R/M) system LlaCI have been
      found on the naturally occurring 7.0 kb plasmid pAW153 in L. lactis subsp.
      cremoris W15. The R/M system was isolated on a chloramphenicol resistant
      derivative of the wild type plasmid (pAW153cat). Plasmid pAW153cat and a 2.4 kb
      HincII-SphI fragment cloned into a high- and a low-copy vector conferred
      decreased sensitivity in L. lactis LM2301 and L. lactis SMQ86 against small
      isometric-headed phages of the 936 or P335 species, respectively. Increased
      plasmid copy number enhanced the level of phage restriction. Sequencing the 2.4
      kb HincII-SphI fragment revealed two open reading frames arranged convergently
      with a 94 bp separation. IlaCIM showed 66% identity to hindIIIM, and IlaCIR
      showed 45% identity to hindIIIR. The organization of the LlaCI operon differs
      from the HindIII operon, where the endonuclease and methylase genes overlap and
      are transcribed in the same direction. The LlaCI methylase is predicted to be 296
      amino acids long, with 63% identity to the HindIII methylase, while the LlaCI
      endonuclease is predicted to consist of 324 or 332 amino acids, depending on the
      position of the start codon. It shows 24% identity to the HindIII endonuclease.

PMID- 9628337
TI  - How is modification of the DNA substrate recognized by the PvuII restriction
      endonuclease?
AB  - In restriction-modification systems, cleavage of substrate sites in cellular DNA
      by the restriction endonuclease is prevented by the action of a cognate
      methyltransferase that acts on the same substrate sites. The PvuII restriction
      endonuclease (R.PvuII) has been structurally characterized in a complex with
      substrate DNA (Cheng et al., 1994) and as an apoenzyme (Athanasiadis et al.,
      1994). We report here a structure, determined to 1.9 A resolution by
      crystallography, of a complex between R.PvuII and iodinated DNA. The presence of
      an iodine at the 5-carbon of the methylatable cytosine results in the following
      changes in the protein: His84 moved away from the modified base; this movement
      was amplified in His85 and disrupts an intersubunit hydrogen bond; and the base
      modification disturbs the distribution of water molecules that associate with
      these histidine residues and the area of the scissile bond. Considering these
      observations, hypotheses are given as to why a similar oligonucleotide, where a
      methyl group resides on the 5-carbon of the methylatable cytosine, is slowly
      cleaved by R.PvuII (Rice et al., 1995).

PMID- 9628338
TI  - Mutational analysis of the function of Met137 and Ile197, two amino acids
      implicated in sequence-specific DNA recognition by the EcoRI endonuclease.
AB  - The gene encoding the EcoRI endonuclease was altered by site-directed mutagenesis
      to introduce multiple substitutions of M137 and 1197, two amino acids which were
      suggested by the revised crystal structure to mediate recognition of the
      cytosines in the 5'-GAATTC-3' target sequence. Eight substitutions of M137 and
      ten substitutions of 1197 were isolated. With the exception of M137W, M137P and
      M137K, all mutant enzymes retained enough activity to damage cellular DNA in the
      absence of the EcoRI methyltransferase. All M137 replacements abolished the
      ability of the enzyme to restrict phage growth. Conservative replacements at 1197
      (L, V) did not impair phage restriction, whereas non-conservative changes reduced
      (G, W) or abolished (D, P) restriction. In general, substitutions at M137 were
      more deleterious than substitutions at I197. Double mutants with combinations of
      M137G/A and I197G/A mutations exhibited a phenotype characteristic for the
      respective single M137 mutant. Double mutants carrying combinations of the
      M137G/A replacements and substitutions at R200 were viable even in the absence of
      the methyltransferase, suggesting that disrupting contacts to both bases of the
      GC base pair inactivates the enzyme. None of the replacements resulted in relaxed
      recognition specificity. In summary, our findings are consistent with a role for
      M137 but do not support such a role for I197 in substrate recognition by the
      EcoRI endonuclease.

PMID- 9628339
TI  - The mechanism of DNA cleavage by the type II restriction enzyme EcoRV: Asp36 is
      not directly involved in DNA cleavage but serves to couple indirect readout to
      catalysis.
AB  - Three different mechanisms have been proposed to describe DNA cleavage by the
      type II restriction endonuclease EcoRV, which differ in the number and function
      of metal ions directly involved in catalysis and the different roles assigned to
      amino acid residues in the active sites and a phosphate group of the substrate.
      There are only four acidic amino acid residues close to the scissile bond: the
      essential Asp74 and Asp90, the non-essential Glu45, and Asp36. We show here that
      Asp36 can be exchanged for alanine, with only minor effects on the cleavage rate
      of the nearby phosphodiester bond, excluding that Asp36 could be directly
      involved in catalysis. Hence, the two versions of the two-metal-ion mechanism are
      not compatible with the experimental data, because too few ligands for two metal
      ions are present near the active site of EcoRV. Our result, thus, supports the
      one-metal-ion mechanism for EcoRV. We suggest that Asp36 has an allosteric effect
      by which specific contacts between one strand of the DNA and one subunit of the
      enzyme trigger the activation of one catalytic center. Given the similar
      structures of the active sites of EcoRV, EcoRI, BamHI, PvuII and FokI, as well as
      the occurrence of a characteristic catalytic motif in several other restriction
      enzymes, we conclude that these enzymes most likely share a similar mechanism of
      DNA cleavage, whose characteristic feature is the involvement of only one Mg2+
      ion in catalysis.

PMID- 9628340
TI  - Functional mapping of the EcoRV DNA methyltransferase by random mutagenesis and
      screening for catalytically inactive mutants.
AB  - M.EcoRV is an alpha-adenine DNA methyltransferase. According to structure
      predictions, the enzyme consists of a catalytic domain, which has a structure
      similar to all other DNA-methyltransferases, and a smaller DNA-recognition
      domain. We have investigated this enzyme by random mutagenesis, using error-prone
      PCR, followed by selection for catalytically inactive mutants. 20 single mutants
      were identified that are completely inactive in vivo as His6- and GST-fusion
      proteins. 13 of them could be overexpressed and purified. All of these mutants
      are also inactive in vitro. 5 of the mutations are located near the putative
      binding site for a flipped adenine residue (C192R, D193G, E212G, W231R, N239H).
      All of these variants bind to DNA, demonstrating the importance of this region of
      the protein in catalysis. Only the W231R mutant could be purified with high
      yields. It binds to DNA and AdoMet and, thus, behaves like a bona fide active
      site mutant. According to the structure prediction Trp231 corresponds to Val121
      in M.HhaI, which forms a hydrophobic contact to the flipped target cytosine. 4 of
      the remaining purified variants are located within a small region of the putative
      DNA-recognition domain (F115S, F117L, S121P, C122Y). F117L, S121P and C122Y are
      unable to bind to DNA, suggesting a critical role of this region in DNA binding.
      Taken together, these results are in good agreement with the structural model of
      M.EcoRV.

PMID- 9628341
TI  - Phage T4 DNA [N6-adenine] methyltransferase: kinetic studies using
      oligonucleotides containing native or modified recognition sites.
AB  - The DNA-[N6-adenine] methyltransferase of T4 phage (T4 Dam MTase) catalyzes
      methyl group transfer from S-adenosyl-L-methionine (AdoMet) to the N6-position of
      adenine in the palindromic sequence, GATC. We have investigated the effect of
      eliminating different structural components of the recognition site on the
      ability of a substrate to be bound and methylated by T4 Dam. For this purpose,
      steady state binding (by gel shift assays) and kinetic parameters of methylation
      (using the methyl donor, [3H-CH3]-AdoMet, at 25 degrees C) were studied using
      various synthetic duplex oligonucleotides containing some defect in the DNA
      target site; e.g., the absence of an internucleotide phosphate or a nucleotide(s)
      within the recognition site, or a single stranded region. The salient results are
      summarized as follows: (1) Addition of T4 Dam to a complete reaction mixture
      (with a 20-mer duplex as substrate) resulted in a 'burst' of 3H-methylated
      product, followed by a constant rate of product formation that reflected
      establishment of steady-state conditions. This suggests that the rate-limiting
      step is release of product methylated DNA from the enzyme [and not the transfer
      of the methyl group]. (2) A number of the defects in duplex structure had only a
      weak influence on the binding and Km values, but strongly reduced the kcat. At
      the same time, several poorly bound duplexes retained good substrate
      characteristics, especially duplexes having uninterrupted GAT-sequences in both
      strands. Whereas having only one half of the recognition site element intact was
      sufficient for stable complex formation, the catalytic turnover process had a
      strict requirement for an uninterrupted GAT-sequence on both strands. (3) There
      was no correlation between Km and binding capability; the apparent Kd for some
      duplexes was 5-70 times higher than Km. This indicates that the T4 Dam
      methylation reaction can not be explained by a simple Michaelian scheme.

PMID- 9628342
TI  - Chimeric restriction enzyme: Gal4 fusion to FokI cleavage domain.
AB  - Gal4, a yeast protein, activates transcription of genes required for metabolism
      of galactose and melibiose. It binds as a dimer to a consensus palindromic 17
      base pair DNA sequence. It is a member of the third family of proteins that
      contain zinc-mediated peptide loops that interact specifically with nucleic
      acids. Gal4 has a very distinctive zinc coordination profile and mode of DNA
      binding. Here, we report the creation of a novel site-specific endonuclease by
      linking the N-terminal 147 amino acids of Gal4 to the cleavage domain of FokI
      endonuclease. The fusion protein is active and under optimal conditions, binds to
      a 17 bp consensus DNA site and cleaves near this site. As expected, the cleavage
      occurs on either side of the consensus binding site(s).

PMID- 9628343
TI  - Protein-protein and protein-DNA interactions in the type I restriction
      endonuclease R.EcoR124I.
AB  - The type I restriction-modification system EcoR124I recognizes and binds to the
      split DNA recognition sequence 5'-GAAN(6)RTCG-3'. The methyltransferase,
      consisting of HsdM and HsdS subunits with the composition M2S, can interact with
      one or more subunits of the HsdR subunit to form the endonuclease. The
      interaction of the methyltransferase with HsdR has been investigated by surface
      plasmon resonance, showing that there are two non-equivalent binding sites for
      HsdR which differ in binding affinity by at least two orders of magnitude. DNA
      footprinting experiments using Exonuclease III suggest that the addition of HsdR
      to the methyltransferase (at a stoichiometry of either 1:1 or 2:1) increases the
      stability of the resulting DNA-protein complex but does not increase the size of
      the footprint. More extensive in situ footprinting experiments using copper
      phenanthroline on the DNA-protein complexes formed by M2S, R1M2S and R2M2S also
      show no difference in the detailed cleavage pattern, with approximately 18
      nucleotides protected on both strands in each complex. Thus the HsdR subunit(s)
      of the endonuclease stabilise the interaction of the M2S complex with DNA, but do
      not directly contribute to DNA binding. In addition, the thymidine nucleotide in
      the tetranucleotide recognition sequence GTCG is hyper-reactive to cleavage in
      each case, suggesting that the DNA structure in this region is altered in these
      complexes.

PMID- 9628344
TI  - Expression and characterisation of the N-terminal fragment of the HsdS subunit of
      M.EcoR124I.
AB  - The type IC modification methyltransferase M.EcoR124I is a trimeric enzyme of 162
      kDa consisting of two copies of the modification subunit, HsdM, and a single DNA
      specificity subunit, HsdS. Studies to date have been largely restricted to the
      HsdM subunit or the intact methyltransferase, since the HsdS subunit is insoluble
      when expressed independently of HsdM. Using PCR, we have cloned and expressed 13
      fragments of the gene for the HsdS subunit, including the sequences encoding each
      of the variable and conserved domains and various combinations of these. Only two
      of these fragments were found to be soluble, a 8.6 kDa fragment (S11) comprising
      the central conserved domain and a 25 kDa N-terminal fragment (S3) containing the
      N-terminal variable domain and the central conserved domain. Analysis of the
      larger of these fragments by gel retardation shows that the protein binds DNA in
      the presence of HsdM at a subunit stoichiometry of 1:1. Gel filtration and CD
      spectroscopy indicate that the protein is monomeric and predominantly alpha
      helical.

PMID- 9628345
TI  - Functional analysis of conserved motifs in type III restriction-modification
      enzymes.
AB  - EcoP1I and EcoP15I are members of type III restriction-modification enzymes.
      EcoPI and EcoP15I DNA methyltransferases transfer a methyl group from S-adenosyl
      L-methionine (AdoMet) to the N6 position of the second adenine residues in their
      recognition sequences, 5'-AGACC-3' and 5'-CAGCAG-3' respectively. We have altered
      various residues in two highly conserved sequences, FxGxG (motif I) and DPPY
      (motif IV) in these proteins by site-directed mutagenesis. Using a mixture of in
      vivo and in vitro assays, our results on the mutational analysis of these
      methyltransferases demonstrate the universal role of motif I in AdoMet binding
      and a role for motif IV in catalysis. All six cysteine residues in EcoP15I DNA
      methyltransferase have been substituted with serine and the role of cysteine
      residues in EcoP15I DNA methyltransferase catalysed reaction assessed. The Res
      subunits of type III restriction enzymes share a distant sequence similarity with
      and contain the motifs characteristic of the DEAD box proteins. We have carried
      out site-directed mutagenesis of the conserved residues in two of the helicase
      motifs of the EcoP1I restriction enzyme in order to investigate the role of
      motifs in DNA cleavage by this enzyme. Our findings indicate that certain
      conserved residues in these motifs are involved in ATP hydrolysis while the other
      residues are involved in coupling restriction of DNA to ATP hydrolysis. Taken
      collectively, these results form the basis for a detailed structure-function
      analysis of EcoP1I and EcoP15I restriction enzymes.

PMID- 9628346
TI  - Sequence specific modulation of DNA restriction enzyme cleavage by minor groove
      binders.
AB  - The inhibition of restriction endonuclease cleavage by a series of bisquaternary
      ammonium derivatives (BQA-derivatives) which bind to the minor groove of DNA has
      been studied. The derivatives considered included six sequence-selective binders
      (SN 6570, SN 6999, SN 6050, SN 6132, SN 6131 and SN 18071) and four non-specific
      binders (SN 6113, SN 5754, SN 6324 and SN 4094) and can be distinguished by their
      activity on restriction endonucleases. Digestion experiments with pUC19 DNA were
      monitored electrophoretically using the transition of the covalently closed
      circular (ccc) DNA into the linear double stranded (lds) one. Only the sequence
      specific binders inhibit the cleavage activity of restriction endonucleases
      EcoRI, SspI and DraI with four and six dAdT-base pairs within their restriction
      sites, while the activity of SalI and BamHI with less than four dAdT-sequences
      was unaffected. In contrast, the non-specific binding ligands were incapable of
      suppressing enzyme digestion. The inhibition of the restriction endonuclease
      PvuII indicates that ligand binding in close vicinity to the cleavage sites is
      also involved in the enzyme inhibition. The dAdT-content in proximity to the
      palindromic sequences of three DraI cutting sites in pUC19 DNA explains why the
      derivative SN 6053 protects these sequences in different manners. Gel shift
      experiments indicated that BQA-derivatives inhibit the DNA-enzyme complex
      formation if the ligand was added to the DNA before the enzyme. In contrast,
      complex formation between DNA and enzyme remained unchanged when the enzyme was
      added first.

PMID- 9628347
TI  - Studies on the synthesis of oligonucleotides containing photoreactive
      nucleosides: 2-azido-2'-deoxyinosine and 8-azido-2'-deoxyadenosine.
AB  - Oligonucleotides containing the photoreactive nucleosides 2-azido-2'-deoxyinosine
      and 8-azido-2'-deoxyadenosine have been prepared using protected 2-fluoro-2'
      deoxyinosine and 8-bromo-2'-deoxyadenosine phosphoramidites. After the assembly
      of the oligonucleotides, the nucleoside derivatives are converted to the
      corresponding azido derivatives by treatment with lithium azide in dry DMF.
      Deprotection of oligonucleotides carrying these azidonucleosides is performed
      with concentrated ammonia at room temperature.

PMID- 9628348
TI  - Genomic structure of the human DNA methyltransferase gene.
AB  - We determined the genomic structure of the gene encoding human DNA
      methyltransferase (DNA MTase). Six overlapping human genomic DNA clones which
      include all of the known cDNA sequence were isolated. Analysis of these clones
      demonstrates that the human DNA MTase gene consists of at least 40 exons and 39
      introns spanning a distance of 60 kilobases. Elucidation of the chromosomal
      organization of the human DNA MTase gene provides the template for future
      structure-function analysis of the properties of mammalian DNA MTase.

PMID- 9628349
TI  - Analysis of methylation in the 5' region of the human alpha-galactosidase A gene
      containing a binding site for methylated DNA-binding protein/RFX1-4.
AB  - We examined methylation in the 5' untranslated region and surrounding sequences
      of the X-linked human alpha-galactosidase A gene. This region includes a
      methylation-dependent binding site for the MDBP/RFX1-4 transcription factor
      family. By bisulfite-based genomic sequencing, we determined the distribution of
      5-methylcytosine residues from position +28 to +143 relative to the major
      transcription start site of the gene in almost 500 molecular clones from
      different tissues and individuals. The CpG methylation patterns in DNA from
      females differed from molecule to molecule with no indication of tissue
      specificity or age-dependence. In contrast, the CG dinucleotides within this
      region were completely unmethylated in almost all of the DNA molecules cloned
      from male tissues. In female eutherian mammals, 50% of the molecules are expected
      to be methylated in an X-linked gene region in which methylation is coupled to
      gene silencing. Of the cloned DNA molecules from female tissues, 40% had 4 or
      more of the 9 CpG's methylated and the MDBP site was methylated in about one
      fifth of the female tissue-derived DNA molecules.

PMID- 9628350
TI  - Accumulating mutations of p53 in colon tumor and hairy cell leukemia do not arise
      from methylation/deamination processes, but rather from nucleotide deletions and
      insertions.
AB  - Mutations of the p53 gene may alter the specific regulatory domains of the
      protein. We examined the conserved domains III, IV and V by SSCP using PCR
      primers covering exons 5, 6, 7 and 8 from hairy cell leukemia (HCL), polyps,
      colorectal and gastric carcinomas. A low rate of p53 mutations was detected in
      HCL and polyps. These mutations may predict the risk of malignant development.
      However, multiple mutations were a frequent occurrence in tumors. Sequence
      analysis of our samples did not demonstrate the high frequency of transition
      mutations (C-->T) that would be predicted if the major course of p53 mutations is
      deamination of 5-methylcytosine (5mC). Rather, most mutations were found to be
      single base insertions or deletions.

PMID- 9628351
TI  - Correlation between transcription and C to T mutations in the non-transcribed DNA
      strand.
AB  - We recently showed that transcription can promote C to T mutations in the non
      transcribed strand in E. coli. To study the relationship between the level of
      transcription and mutant frequency, an inactive allele of the kanamycin
      resistance gene was expressed under the control of a hybrid promoter consisting
      of an UP element and the tac promoter. When this promoter is induced, the
      frequency of C to T mutations in the non-transcribed strand increases in rough
      proportion to the amount of mRNA. At the highest level of transcription at which
      cell growth is not affected, there is about a 10-fold increase in the frequency
      of mutations. This result is consistent with the hypothesis that transcription
      forces the non-transcribed strand to be in a single-stranded state and that this
      results in frequent C to T mutations.

PMID- 9628352
TI  - Chromosomal inactivation of Bacillus subtilis exfusants: a prokaryotic model of
      epigenetic regulation.
AB  - Epigenetic mechanisms are not exclusively reserved to eukaryotic organisms. They
      are also observed in prokaryotes. As described first by Hotchkiss and Gabor,
      protoplast fusion between strains of Bacillus subtilis produces heterodiploid
      cells. Heterodiploidy is associated with the inactivation of one of the
      chromosomes. To study the physical structure of the fusion product and the
      molecular mechanisms of inactivation, we constructed heterodiploid clones
      containing two chromosomes labeled by a NotI restriction fragment length
      polymorphism. In the progeny, we identified haploid recombinant clones that
      contain a chromosome carrying large regions of inactivated DNA. Studies of both
      recombinants of the latter kind and heterodiploid cells indicated that
      chromosomal inactivation was not determined by alteration of the inactivated
      nucleotide sequence, but was probably due to a modification in the structure of
      the bacterial chromatin.

PMID- 9628353
TI  - Analysis of DNA methylation processes related to the inhibition of DNA synthesis
      by 5-azacytidine in Streptomyces antibioticus ETH 7451.
AB  - 5-Azacytidine inhibits DNA synthesis and to a lesser proportion RNA synthesis in
      S. antibioticus. The biosynthesis of proteins is not affected. The main
      inhibitory effect of 5-azacytidine on DNA and RNA synthesis is probably caused by
      its incorporation into newly synthesized DNA or RNA and the formation of covalent
      complexes between cytosine-specific methyltransferases and the modified DNA or
      RNA templates. To analyze whether such effects could occur at the oriC region of
      S. antibioticus we analyzed the methylation status of this region using the
      bisulphite assisted genomic sequencing method. One of the cytosine residues found
      to be partially methylated was contained within an unique NaeI sequence (GCCGGC)
      in oriC. Subsequent analysis shows chromosomal DNA from S. antibioticus to be
      resistant to R.NaeI restriction indicating that this strain contains a NaeI
      specific cytosine C5-methyltransferase activity. Following 5-azacytidine
      treatment the NaeI site within the oriC region becomes partially demethylated.
      Our results suggest that some of the 5-azacytidine effects on DNA and RNA
      synthesis might indeed be related to the complex formation and inhibition of a
      cytosine-specific DNA methyltransferase.

PMID- 9628354
TI  - An experimental selection system to identify bacterial cells exhibiting a new DNA
      host specificity.
AB  - Restriction-modification enzymes interact with DNA sequences in a highly specific
      manner. Mutations within the DNA binding region of the enzymes could be expected
      to produce enzyme variants with changed DNA sequence specificities. We developed
      an efficient in vivo selection system that enabled us to detect one cell coding
      for a restriction-modification system with a new DNA sequence specificity in a
      background of more than 10(6) cells with the original DNA sequence specificity.

PMID- 9628355
TI  - Cloning and characterization of the gene encoding M.FauI DNA methyltransferase.
AB  - The enzymes of the FauI restriction-modification system from the Flavobacterium
      aquatile strain recognize the non-palindromic sequence 5'-CCCGC-3'/3'-GG-GCG-5'.
      We have cloned the gene encoding the DNA modifying component of this system and
      determined its nucleotide sequence. The deduced amino acid sequence contains ten
      conserved motifs characteristic for [cytosine-5] DNA methyltransferases. Part of
      the gene sequence that encodes the putative target recognizing domain of the
      M.FauI shows some homology with the downstream region, thus indicating that
      duplication of the DNA segment was probably involved in the gene evolution.

PMID- 9628356
TI  - A pair of single-strand and double-strand DNA cytosine-N4 methyltransferases from
      Bacillus centrosporus.
AB  - Sequence analysis of the BcnI restriction-modification system revealed the
      presence of an open reading frame encoding a second cytosine-N4
      methyltransferase, M.BcnIA, in the vicinity of the genes specifying the
      previously characterized cytosine-N4 methyltransferase M.BcnIB and restriction
      endonuclease R.BcnI. Both methyltransferases were purified from the E. coli cells
      expressing the individual genes, and their enzymatic efficiencies in vitro were
      compared with a variety of DNA substrates. Both enzymes act on 5'-CC(C/G)GG-3'
      sites in double-stranded DNA, however, M.BcnIA can also, with a comparable
      efficiency, modify the specific targets in single-stranded DNA. The biological
      significance of the presence of the tandem methyltransferases in the BcnI system
      is discussed.

PMID- 9628357
TI  - Actinobacillus and Streptococcus: producers of isoschizomers of the restriction
      endonucleases R.HphI, R.SauI, R.NheI, R.MboI and R.SwaI.
AB  - New restriction endonucleases have been found in microorganisms isolated from the
      microflora of human teeth. The strain-producers are Actinobacillus suis and
      Streptococcus milleri. The new enzymes are isoschizomers of the prototypes as
      follows: AsuHPI - HphI; AsuSAI - SauI; AsuNHI - NheI; AsuMBI and SmiMBI - MboI;
      SmiI - rare-cutter SwaI.

PMID- 9628358
TI  - Sequence similarities between the genes encoding the S.NgoI and HaeII
      restriction/modification systems.
AB  - The DNA sequence encoding the S.NgoI restriction/modification (R/M) system was
      identified from a gene bank made from Neisseria gonorrhoeae strain WR302 by
      identifying recombinant plasmids that induced the reporter system in a methylase
      detection strain AP1-200-9 (Piekarowicz et al., 1991) and were resistant to
      digestion with NgoI. The DNA sequence was determined from one of these (pUCP30).
      M.NgoI is a protein of 315 aa with a predicted MW of 35296 Da and R.NgoI is a
      protein of 350 aa with a predicted MW of 40650 Da. The termination codon of
      M.NgoI overlapped the start codon of R.NgoI. The same strategy was used to clone
      the R/M system encoding HaeII from Haemophilus aegyptius strain ATCC 11116. The
      DNA sequence from one clone representing this class (pAP704) was determined.
      HaeII methylase is a protein of 318 aa with a predicted MW of 35669 Da and
      R.HaeII contains 352 aa with a predicted MW of 40800 Da. aa alignments between
      the two methylases indicated that they were 74.3% identical and 79% similar. DNA
      sequence alignments revealed 68% identity. An aa alignment between the two
      restriction enzymes indicated that they were 60% identical and 68% similar. DNA
      sequence alignments revealed 61% identity. The DNA sequences flanking these two
      systems were identified and used to determine the genomic organization of the two
      systems. The S.NgoI genes were found between two genes, one with high homology to
      GTP binding proteins of unknown function and one with homology to genes involved
      in tRNA synthetase synthesis. The HaeII R/M genes were located between two genes,
      mucF and mucE. The DNA sequence of the HaeII R/M system was compared to the
      genomic DNA sequence of H. influenzae Rd. Although the DNA sequences flanking the
      HaeII system were > 99% identical to contiguous DNA fragments found in the genome
      of H. influenzae Rd, no homology was seen with the DNA sequences encoding the
      HaeII R/M system, indicating that it is not found in this strain. Given the vast
      difference in the GC content of S.NgoI and HaeII, their apparent insertion into
      polycistronic operons, and their difference in codon usage when compared to the
      species from which they were isolated, the data suggest that these R/M systems
      originated in an organism other than Neisseria or Haemophilus.

PMID- 9628359
TI  - Design of a novel regulatory circuit for expression of restriction endonucleases.
AB  - We have developed a new strategy with a very tight control for the expression of
      cloned genes. The system employed here is the T7 promoter-based expression system
      in which transcription activator protein C of bacteriophage Mu (Mu C) has been
      cloned to serve as a repressor in the regulatory circuit. The system also
      includes pLysE, which encodes T7 lysozyme, an inhibitor of T7 RNA polymerase.
      This ensures tight regulation of cloned genes in the uninduced state. Upon
      induction, the expressed Mu C protein binds to its cognate site thereby
      repressing lys transcription driven by the tet promoter. In order to evaluate the
      tight control achieved in the system, and to check leaky expression, if any, we
      have cloned the gene for the SmaI restriction endonuclease without its cognate
      methylase. For this purpose, a dicistronic unit was constructed by cloning the
      smaIR gene downstream of the Mu C gene. SmaI expression was observed only in the
      induced cell extracts, demonstrating a tight control. The system could be used to
      express the genes of other cloned restriction enzymes and has the potential for
      general applications.

PMID- 9628360
TI  - Establishment of a hybrid SalI-HgiDII type II restriction-modification system.
AB  - In the SalI system, endonuclease activity can be only achieved in the presence of
      a functional modification gene. Thus, the DNA methyltransferase is involved in
      the control of restriction. By fusion of the restriction gene of the SalI system
      to the modification gene of the isospecific HgiDII system a hybrid type II
      restriction-modification system was created. Although in the hybrid situation the
      level of endonuclease activity was significantly lower than in the natural
      system, the HgiDII modification enzyme clearly supports SalI restriction. The
      mechanism by which the two isospecific methyltransferases control restriction is
      currently under study.

PMID- 9628361
TI  - Isolation of a non-classical mutant of the DNA recognition subunit of the type I
      restriction endonuclease R.EcoR124I.
AB  - We have used deletion mutagenesis and PCR-based misincorporation mutagenesis to
      produce a collection of mutations in the central conserved region of the DNA
      binding subunit of the type IC restriction endonuclease EcoR124I. It has been
      proposed that this domain is involved in protein-protein interactions during the
      assembly of the endonuclease. While a large percentage of these mutations gave a
      classical Res- Mod- phenotype, one mutant was isolated with a nonclassical Res-
      Mod+ phenotype. The loss of restriction activity, but retention of the ability to
      modify indicates that this mutation cannot affect DNA binding and must alter the
      assembly of the endonuclease in such a way as to prevent DNA cleavage but allow
      methylation. This mutant resulted from a single amino acid change Trp212-->Arg.
      The location of the single amino acid change is at the border of the central
      conserved region and the second target recognition domain (TRD2) and suggests
      that this region is extremely important for the assembly of the methylase with
      the HsdR subunit into a functional restriction endonuclease.

PMID- 9628362
TI  - Substitution of the conserved phenylalanine in the S-adenosyl-L-methionine
      binding site of M.MspI with tyrosine modifies the kinetic properties of the
      enzyme.
AB  - Cytosine (C-5)-specific DNA methyltransferases share a set of ten conserved
      motifs distributed evenly throughout the entire polypeptide chain. The first
      conserved motif contains a Phe, which is intimately associated with cofactor
      recognition. In the pseudo-DNA methyltransferase M.SpoI, encoded by the pmt1 gene
      in Schizosaccharomyces pombe, a Tyr replaces this Phe residue. We describe the
      properties of a mutant form of M.MspI, a typical cytosine (C-5)-specific DNA
      methyltransferase, in which Tyr replaces the conserved Phe. This mutant shows
      differences in ternary complex formation and in the pattern of covalent complex
      formation with an inhibitory, fluorinated DNA duplex which may be due to
      anomalous hydrogen bonding between the mutant Tyr hydroxyl group and the
      catalytic loop of the enzyme or through interference with cofactor binding.

PMID- 9628363
TI  - Ca2+-ions stimulate DNA binding specificity of Cfr10I restriction enzyme.
AB  - The Cfr10I restriction enzyme recognizes the degenerate hexanucleotide sequence
      5'-Pu/CCGGPy-3' and cleaves it as indicated. DNA binding studies of Cfr10I
      endonuclease were performed using gel mobility shift assay. Analysis of Cfr10I
      binding to DNA revealed that in the absence of metal ions Cfr10I binds to DNA
      containing or lacking the recognition sequence with similar low affinity.
      Addition of Ca2+ to the binding buffer stimulated manifestation of DNA binding
      specificity of Cfr10I.

PMID- 9628364
TI  - Phosphorothioate substrates for the SfiI restriction endonuclease.
AB  - Oligodeoxynucleotides carrying the recognition sequence for the SfiI endonuclease
      were synthesised with phosphorothioates at the cleavage site. The Rp and Sp
      diastereoisomers of the oligonucleotides were separated by HPLC using a mobile
      phase containing L-cysteine. The duplex with Rp phosphorothioates was cleaved
      very slowly in the presence of Mg2+, though virtually complete cleavage was
      obtained with Mn2+. No significant cleavage of the duplex with Sp
      phosphorothioates occurred with either Mg2+ or Mn2+. When added to a plasmid with
      one SfiI site, the duplexes with either Rp or Sp phosphorothioates inhibited the
      rate at which SfiI cleaved the plasmid: a control duplex with oxyester linkages
      enhanced the rate of plasmid cleavage. In contrast to type IIe nucleases such as
      EcoRII and NaeI, which can be activated by non-hydrolysable analogues of their
      substrates, SfiI reactions require four susceptible phosphodiester bonds.

PMID- 9628365
TI  - Does BcgI, a unique restriction endonuclease, require two recognition sites for
      cleavage?
AB  - BcgI is a multi-subunit restriction-modification (R-M) complex. BcgI prefers
      pBR322 DNA over pUC19 in a DNA cleavage reaction. Linearized pBR322 contains two
      BcgI recognition sites and pUC19 has only one site. To test whether two target
      sites are required for BcgI cleavage, one of the two sites in pBR322 was deleted,
      and as a result pBR322-1 became a poor substrate for BcgI. Conversely, adding a
      BcgI site to pUC19 makes it a much better substrate for BcgI cleavage. In
      addition, the BcgI (R-M) complex forms a heterohexamer in solution that is
      capable of interacting with two recognition sites. Our results suggest that BcgI
      requires two recognition sites for cleavage.

PMID- 9628366
TI  - Dependence of McrBC cleavage on distance between recognition elements.
AB  - DNA cleavage by the modification-dependent restriction enzyme McrBC requires the
      presence of two suitably modified recognition elements appropriately spaced in
      the substrate. To characterize the spacing requirement in more detail, we have
      constructed a plasmid with a single McrBC cleavage site, in which the distance
      between recognition elements could be systematically varied while preserving the
      local sequence surrounding the recognition elements. Optimal separation between
      elements was 55-103 basepairs, with detectable cleavage observed at spacing of 32
      bp to 2 kb; no cleavage was seen with spacing of 22 bp or less or with 3 kb
      between elements. Changing the spacing by 4 basepairs within the optimal range
      had little effect on the efficiency of cleavage, suggesting that the recognition
      elements need not lie on the same face of the DNA helix.

PMID- 9628367
TI  - Mutual activation of two restriction endonucleases: interaction of EcoP1 and
      EcoP15.
AB  - Type III restriction endonucleases recognize nonsymmetric nucleotide sequences. A
      necessary condition for DNA cleavage is the presence of two unmethylated
      recognition sites which are inversely ('head-to-head') oriented in the DNA double
      strand. A DNA substrate possessing one EcoP1 and one EcoP15 site in the head-to
      head configuration could not be cleaved by the individual enzymes, however, it
      was specifically digested in the simultaneous presence of both enzymes. In
      agreement with the tracking-collision model for the DNA interaction of type III
      enzymes cleavage could be abolished by Lac repressor bound between the two sites.
      We conclude that two different type III enzymes can functionally cooperate in the
      cleavage of DNA.

PMID- 9628368
TI  - Escherichia coli bacteriophage T1 DNA methyltransferase appears to interact with
      Escherichia coli enolase.
AB  - Infection of Escherichia coli cells with bacteriophage T1 induces synthesis of a
      bacteriophage-specific DNA methyltransferase (M.EcoT1, EC No: 2.1.1.72) with a
      specificity for adenine residues in the sequence 5'-GATC-3'. Purification of
      M.EcoT1 allowed the determination of the coding sequence of the gene (Schneider
      Scherzer et al., 1990). The peptide of the entire coding sequence was over
      expressed as a histidine-hexapeptide tagged protein in E. coli. Affinity
      purification using a Ni2+ chelating (Ni-NTA) resin yielded a recombinant enzyme
      with almost the same enzymatic properties as the protein purified from T1
      infected E. coli cells. Interestingly, in both purification procedures, a protein
      with a molecular weight of 50000 was found to copurify with M.EcoT1. The N
      terminal amino acid sequence identified these proteins in both cases as E. coli
      enolase (EC No: 4.2.1.11).

PMID- 9628369
TI  - Restriction endonucleases can be used to confirm a structure of unusual DNA
      duplexes.
AB  - Cyclic and polycyclic oligonucleotides were synthesized using chemical ligation.
      Two types of catenanes with one and several intertwinings were produced. The
      yield of these molecules depended on the ligation conditions and nucleotide
      sequence of the ligated oligonucleotide and its template. Structure of ligation
      products was investigated and confirmed using restriction endonuclease MvaI.
      Interaction of the synthesized molecules with restriction endonucleases SsoII,
      EcoRII and HindIII was also studied.

PMID- 9628370
TI  - Deep hypothermia and circulatory arrest for surgery of complex intracranial
      aneurysms.
AB  - OBJECTIVE: Some intracranial aneurysms may not be operable by conventional
      neurosurgery due to their location or morphology. Cardiopulmonary bypass (CPB)
      and deep hypothermic circulatory arrest renders surgery of these complex
      aneurysms possible. Brain temperatures can be measured directly in this setting.
      METHODS: Eight patients with complex intracranial aneurysms were operated on with
      the aid of CPB. Femoro-femoral bypass with heparin-coated circuit components was
      used in all cases. Venous drainage was augmented by a centrifugal pump in six
      patients and by a newly developed vacuum technique in two patients. Temperatures
      were monitored by probes in brain, tympanum, nasopharynx, bladder, rectum,
      arterial and venous blood. These measurements were recorded on-line together with
      those of cerebral oxygen saturation, AP, CVP and PAP. Blood gas analyses and an
      EEG were also performed continuously. RESULTS: Outcome was excellent in seven
      patients, in one patient moderate neurological disability occurred. Mean time on
      cardiopulmonary bypass was 160 (117-215) min, for cooling to a brain temperature
      of 18 degrees C 33 (20-47) min, and for total circulatory arrest 27 (15-45) min.
      Additionally, terminal brain arteries were clamped for up to 68 min in four
      patients. No cardiac complications were observed. Actual brain temperatures were
      best reflected by the tympanum probes (max. deviation 2 degrees C), whereas
      temperatures measured in bladder or rectum exhibited deviations of up to 10
      degrees C. EEG activities were arrested between brain temperatures of 19 and 26
      degrees C. CONCLUSIONS: Complex intracranial aneurysms can be treated
      successfully using deep hypothermic circulatory arrest. Extensive monitoring adds
      to the speed and safety of the procedure. The resulting comparative measurements
      of temperatures at different body sites including brain, EEG, and other variables
      may be of general relevance for operations employing deep hypothermia and
      circulatory arrest.

PMID- 9628371
TI  - Intramural hematoma of the thoracic aorta.
AB  - OBJECTIVE: This study was designed to clarify the optimal treatment mode of
      patients with intramural hematoma (IMH) of the thoracic aorta. METHODS: From 1992
      through 1997, 51 patients underwent surgical repair or medical treatment of IMH
      of the thoracic aorta. There were 36 male and 15 female patients, aged between 49
      and 79 years with a mean of 67 years. The ascending aorta and/or aortic arch was
      involved in 18 patients (group I), whereas the descending thoracic aorta was
      affected in 33 (group II). The presence of intimal disruption in IMH was
      confirmed in 10 of group I and 13 of group II patients. RESULTS: For group I
      patients 13 required aortic arch repairs and the remaining 5 underwent
      conservative therapy including anti-hypertensive medication. Primary indications
      for immediate surgery were: cardiac tamponade in 5 patients, aortic dissection
      superimposed on IMH in 2, and persistent pain with an aortic arch aneurysm in 1,
      respectively. Early elective operations were done for enlarged ulcer in 3
      patients and aneurysmal dilatation in 2 of which 1 had a coexisting aortic arch
      aneurysm. The 2-year survival rate after diagnosis was 94% with an operation-free
      rate of 25%. Nine of the group II patients experienced surgical intervention of
      which 8 had intimal disruption, 4 patients received urgent replacement of the
      descending thoracic aorta for massive pleural effusion and 1 had the aortic arch
      replaced for a coexisting aneurysm with persistent pain. All other patients
      underwent conservative treatment and 4 of them had to be shifted to early surgery
      during the initial hospitalization because of an enlarged ulcer. The 5-year
      survival rate in group II patients was 63% with an operation-free survival rate
      of 66%. CONCLUSIONS: On the basis of our experience early operation is
      recommended for almost all patients with ascending aortic IMH, and medical
      therapy for those with descending aortic involvement unless complication
      developed. However, the presence of intimal disruption may require early surgical
      treatment even in the patients with descending thoracic IMH.

PMID- 9628372
TI  - The edge-to-edge technique: a simplified method to correct mitral insufficiency.
AB  - OBJECTIVE: Repair of mitral regurgitation (MR) is more demanding in case of
      prolapse of the anterior leaflet, posterior leaflet with calcified annulus, or
      prolapse of both leaflets. We evaluated a repair which consists of anchoring the
      free edge of the prolapsing leaflet to the corresponding free edge of the facing
      leaflet: the 'edge-to-edge' (E-to-E) technique. The correction results in a
      double orifice valve when the prolapse is in the middle portion of the leaflet
      and in a smaller valve orifice when the prolapse is close to a commissure.
      METHODS: Out of 432 patients with MR submitted to valve repair between January
      1991 and September 1997, 121 (mean age 56 +/- 15.8 years) underwent E-to-E
      correction. The most prevalent etiology was degenerative disease (82 patients,
      68%). The mechanism of MR was anterior leaflet prolapse (61 patients), posterior
      leaflet prolapse (24 patients), prolapse of both leaflets (28 patients) and other
      complex mechanisms (8 patients). In 72 patients, a double orifice was created,
      the paracommissural repair was done in 49 patients. RESULTS: Hospital mortality
      was 1.6%. Overall survival was 92 +/- 3.1% at 6 years with 95 +/- 4.8% freedom
      from reoperation. Mortality was unrelated to the type of repair. Mitral stenosis
      was never observed after the correction. At the follow-up (mean 2.2 +/- 1.5
      years), all patients but 15 are class I or II. Symptoms at the follow-up are not
      related to residual MR. CONCLUSIONS: Midterm results of this alternative repair
      technique are promising, considering the high prevalence of complex anatomical
      lesions. The technique is simple, easily reproducible and rapidly feasible also
      when mitral exposure is suboptimal.

PMID- 9628373
TI  - Improved success rate of the maze procedure in mitral valve disease by new
      criteria for patients' selection.
AB  - OBJECTIVE: We have carried out the maze procedure for atrial fibrillation (AF) as
      a combined operation with mitral valve surgery in a consecutive fashion until
      December 1994 (period 1). Therefore, the success rate in sinus rhythm conversion
      remained unsatisfactory. We have selected the patients according to arbitrarily
      decided new criteria since January 1995 (period 2), and examined the results
      prospectively. METHODS: Between May 1992 and February 1997, we carried out the
      maze procedure in 220 patients as a combined operation with mitral valve surgery.
      During period 2, we carried out the maze procedure in 63 cases who satisfied all
      the new criteria (voltage of f-wave in V1 lead > 0.1 mV, cardiothoracic ratio
      (CTR) < 70%, LA dimension < 70 mm), and 37 patients out of these criteria.
      Success was defined as sinus rhythm restoration without sick sinus syndrome.
      RESULTS: There were 4 hospital deaths (1.8%) and 4 late deaths (1.8%). Success
      rate was significantly (P = 0.0089) higher in period 2 (82%) than in period 1
      (65%). Success rate was significantly higher in patients within criteria than out
      of criteria both in period 1, period 2, and total (77 versus 48%, P = 0.018; 90
      versus 66%, P = 0.004, and 83 versus 55%, P = 0.0001). CONCLUSION: The maze
      procedure is highly reliable when combined with mitral valve surgery if patients
      are selected properly.

PMID- 9628374
TI  - Effect of lung volume reduction surgery on pulmonary hemodynamics in severe
      pulmonary emphysema.
AB  - OBJECTIVE: The presence of pulmonary hypertension in severe pulmonary emphysema
      has been considered a relative contraindication to lung volume reduction surgery
      (LVRS). There was concern that resection of lung tissue might further increase
      pulmonary artery pressure. To address this point, the prevalence of pulmonary
      hypertension in candidates for LVRS was investigated. The changes in pulmonary
      artery pressures after bilateral videoassisted thoracoscopic resection was
      studied in patients with homo- and heterogeneously destroyed emphysematous lungs.
      DESIGN: The pulmonary arterial pressures by right heart catheterization were
      prospectively assessed, before and 6 months after LVRS in 21 consecutive patients
      (15 males, six females, mean (+/- S.E.) age: 62 +/- 1.9, range 42-74 years). All
      were former smokers and three had ZZ-AT1 deficiency. The inclusion criteria were:
      (a) severe bronchial obstruction (FEV1 < 35% predicted); (b) pulmonary
      hyperinflation (RV/TLC > 0.60); and (c) absence of hypercapnia (PaCO2 < 50 mmHg).
      RESULTS: The FEV1 had increased from 28 +/- 2% to 35 +/- 3% of the predicted
      value (P < 0.05) 6 months after surgery. The RV/TLC had declined from 0.65 +/-
      0.02 to 0.55 +/- 0.02; PaO2 increased (66 +/- 1 versus 71 +/- 2 mmHg, P = 0.04),
      PaCO2 (38 +/- 2 versus 36 +/- 1 mmHg, P = 0.26) did not change. The pulmonary
      artery mean pressure (PAPmean) remained unchanged (18 +/- 1 versus 19 +/- 1 mmHg,
      P = 0.26). In six patients PAPmean was > or = 20 mmHg (up to 24 mmHg)
      preoperatively. After 6 months, six patients had a PAPmean > or = 20 mmHg (up to
      31 mmHg). CONCLUSIONS: In patients with severe emphysema who are candidates for
      LVRS (but have only mild to moderate hypoxemia and a PaCO2 < 50 mmHg) we found no
      relevant pulmonary hypertension and pulmonary artery pressure did not change
      significantly after surgery. Therefore, routine right heart catheterization is
      not mandatory for preoperative evaluation.

PMID- 9628375
TI  - Tissue response to biomaterials used for staple-line reinforcement in lung
      resection: a comparison between expanded polytetrafluoroethylene and bovine
      pericardium.
AB  - OBJECTIVE: A study in a canine model of lung-reduction surgery evaluated the
      tissue response to polytetrafluoroethylene (ePTFE) and bovine pericardium (BP)
      used for staple-line reinforcement. METHODS: In each of ten dogs, BP was placed
      in one lung and ePTFE in the other. The implants were retrieved at 30, 95, or 167
      days after implantation and studied histologically. The connective tissue
      covering the implants was measured and analysis of variance was used to compare
      results with the two materials. RESULTS: At 30 days, the BP specimens showed
      focal chronic inflammation and thin tissue coverage, whereas the ePTFE specimens
      had no focal inflammation and thick tissue coverage. At 95 and 167 days, the
      inflammation in the BP specimens had resolved, but tissue coverage remained
      minimal, and there was no resorption of the BP. In the ePTFE specimens, tissue
      coverage had increased. Analysis of variance comparing representative tissue
      specimens showed that the tissue encapsulating the ePTFE was significantly
      thicker than that surrounding the BP (P < 0.0001). No air leaks, staple-line
      disruptions, or infections occurred in the study. CONCLUSIONS: Neither ePTFE nor
      BP is resorbable. Both materials have been used successfully, without resultant
      infections, for clinical staple-line reinforcement. The more favorable tissue
      response to ePTFE observed in this study may have clinical ramifications.
      Comparative clinical studies of the two materials are needed.

PMID- 9628376
TI  - Clinical patterns and trends of outcome of elderly patients with bronchogenic
      carcinoma.
AB  - OBJECTIVE: To investigate the clinical characteristics and determinants of
      operative mortality and long-term survival of elderly patients submitted to
      pulmonary resection for intended cure of lung cancer. METHODS: Retrospective
      analysis of 500 consecutive pulmonary resections performed in patients aged over
      70 years from 1975 to 1996. Predictors of in-hospital mortality were identified
      by univariate and multivariate analyses. Determinants of long-term outcome were
      investigated in all survivors, with no patient being lost to follow-up. RESULTS:
      Mean age was 74 +/- 3 years (maximum: 90), and 36 patients were octogenarians.
      The sex-ratio M:F was 5:3. History of combined cardiovascular or previous
      neoplastic disease was noted in 193 and 63 patients, respectively. The
      predominant histology was squamous cell carcinoma (n = 243), with a significantly
      higher incidence in male than in female. Most patients received standard
      procedures, while 103 patients underwent extended resections for tumors involving
      the mediastinum (n = 44), the chest wall (n = 33), the carina (n = 2) or had a
      sleeve resection of the main bronchus (n = 24). Procedures were considered to be
      complete and curative in 459 patients, among whom 294 had a stage I disease.
      There were 37 (7.4%) in-hospital deaths. Mortality rates following pneumonectomy,
      bilobectomy, lobectomy and lesser resection were 11:136, 4:34, 22:291, and 0:39,
      respectively. Age, male gender, hypertension, low FEV1 and extended procedure
      were identified as independent predictors of early mortality. Overall survival
      rates were 33.7 and 12% at 5 and 10 years, respectively. Multivariate analysis
      demonstrated that the disease stage was the main prognosticator. During the
      follow-up period, cancer recurrence (n = 183; 39.5%) or second primary lung
      cancer (n = 20; 4.3%) occurred in 203 patients, among whom 18 (9%) had a second
      lung resection. Carcinoma in other systems occurred in 25 patients (5.3%), and
      major cardiovascular event in 51 (11%). CONCLUSIONS: Male and squamous cell
      carcinoma are characteristic of elderly patients with resected lung cancer.
      Operative mortality is acceptable for standard resection, and survival figures
      are concordant with those reported in other series which include younger
      patients.

PMID- 9628377
TI  - Cardiorespiratory function before and after operation for pectus excavatum:
      medium-term results.
AB  - OBJECTIVE: The study was undertaken in order to assess the degree of impairment
      of the cardiovascular system in patients with funnel chest and to investigate any
      changes caused by surgical correction. METHODS: Echocardiographic examinations
      with systolic, diastolic and ejection volume indices calculation as well as
      pulmonary function tests were performed before surgery and at medium-term follow
      up on 34 patients who were operated on for pectus excavatum between 1987 and
      1992. RESULTS: The mean age was 13.4 years. There were 70.6% males. Pulmonary
      function was found to be restricted preoperatively in 18 patients. Inspiratory
      vital capacity and forced expiratory volume were increased or did not change at
      follow-up (5 years) in these patients. In cases with normal or moderately
      restricted pulmonary function (inspiratory vital capacity, forced expiratory
      volume more than 75% predicted) the reduction of lung function was noted after
      surgery. Marked haemodynamic improvement was found with the increase of diastolic
      and ejection volume of both heart ventricles (mainly right one). The improvement
      was more evident in patients with severe deformations. CONCLUSION: Only in case
      of severe reduction of lung function in a patient with funnel chest can one
      expect improvement after surgery. Sternocostal elevation improves function of
      both heart ventricles at rest.

PMID- 9628378
TI  - Conversion of complex neonatal Ebstein's anomaly into functional tricuspid or
      pulmonary atresia.
AB  - BACKGROUND: Ebstein's anomaly, due to failure of delamination of one or more
      leaflets of the tricuspid valve (TV), is associated with varying degrees of
      tricuspid regurgitation (TR) and dysplasia of the right ventricle (RV). Although
      refinement of tricuspid valvuloplasty and plication techniques have opened the
      way to a satisfactory outlook for the majority of older children and adults,
      Ebstein's anomaly presenting at neonatal age, secondary to ineffective forward
      flow into the pulmonary and systemic circulation, has a reported mortality rate
      of as high as 75%. In order to improve the dismal outcome in neonatal Ebstein's
      anomaly, we have strived for early univentricular palliation. PATIENTS AND
      METHODS: Univentricular repair was performed in five neonates (median age 5 days;
      range 2-14 days) with Ebstein's anomaly, ductal dependent pulmonary blood flow,
      severe TR, absence of forward flow across the pulmonary valve, and small left
      ventricular (LV) area due to right-to-left bowing of the ventricular septum and
      ineffective LV loading (median indexed LV area 10.5 cm2/m2). In addition, two
      neonates had moderate pulmonary regurgitation (PR), one with additional pulmonary
      stenosis. In all patients, the indexed area of the combined right atrium and
      atrialized RV was greater than that of the combined functional RV, left atrium,
      and left ventricle (median 22.0 and 20.8 cm2/m2, respectively). The median
      preoperative systemic oxygen tension was 35 mmHg and the median pH 7.28. Repair
      consisted of TV closure with a pericardial patch (with the coronary sinus
      draining into the RV) (n = 3) or, in the presence of PR, resection of the
      dysplastic TV and division and oversewing of the main pulmonary artery (n = 2),
      as well as excision of the atrial septum, resection of redundant right atrial
      wall, and construction of an aortopulmonary shunt (n = 5). RESULTS: The median
      indexed LV area increased from 10.5 to 18.8 cm2/m2 as a result of more effective
      loading of the left ventricle. There was no intraoperative or late mortality. The
      patients were extubated at a median of 7 days postoperatively. At discharge, the
      median systemic oxygen tension was 46 mmHg. In all five patients, at 6, 7, 10, 12
      and 16 weeks of age, a bidirectional cavopulmonary anastomosis has been
      constructed. CONCLUSIONS: In neonates with Ebstein's anomaly and ductal dependent
      pulmonary blood flow, rational palliation consists of the surgical creation of
      tricuspid atresia or, in the additional presence of PR or pulmonary stenosis, the
      creation of pulmonary atresia. These procedures may result in effective LV
      decompression and more effective volume loading of the left ventricle with
      increase of systemic output and improved clinical outcome.

PMID- 9628379
TI  - Should coronary artery bypass grafting be performed at the same time as repair of
      a post-infarct ventricular septal defect?
AB  - OBJECTIVE: The value of coronary artery bypass grafting (CABG) at the time of
      repair of a post-infarct ventricular septal defect (VSD) remains controversial.
      The aim of this study was to analyse the effect of CABG on early mortality and
      survival following repair of an acquired VSD. METHODS: Over 23 years, 179
      patients, 118 male, 61 female, mean age 66 years (range 43-80), have undergone
      repair of a post-related VSD in our unit. A total of 29 patients, who
      predominantly form the earlier part of the series, were operated on greater than
      1 month after the infarct and are, therefore, excluded. Coronary angiography was
      performed in 98 (65.3%) of the remaining 150 patients. Of these, 41 had coronary
      artery disease (CAD) limited to the infarct-related vessel and 57 had additional
      significant CAD. Those with CAD limited to the infarct-related vessel were not
      grafted (Group A). Of those, 40 with significant CAD underwent CABG at the time
      of VSD repair (Group B) and 17 did not (Group C). In 52 patients the coronary
      anatomy was not documented (Group D). Risk factors for early mortality were
      evaluated using logistic regression. Actuarial survival was compared using log
      rank and Wilcoxon tests. Cox's proportional hazards method was used to determine
      factors affecting survival. RESULTS: Overall, 30 day mortality was 32%. CABG did
      not significantly decrease operative mortality (logistic regression). There was
      no statistically significant difference in early mortality or actuarial survival
      between the four groups. CABG was not associated with an increased survival
      (Cox's method). CONCLUSIONS: Concomitant CABG at the time of VSD repair does not
      affect early mortality nor confer survival benefits. There seems to be no
      demonstrable benefit in revascularisation at the time of repair and, therefore,
      it may be unnecessary to perform CABG or coronary angiography in these patients.

PMID- 9628380
TI  - Endothelial cell injury in cardiac surgery: salicylate may be protective by
      reducing expression of endothelial adhesion molecules.
AB  - OBJECTIVE: Cardiac surgery with cardiopulmonary bypass induces ischemia to the
      heart, hypoxemia to various tissues and release of endotoxins. The endothelial
      cell may suffer from hypoxia and trigger cascades of adverse reactions by
      activation of neutrophils through adhesion molecules. The authors measured
      expression of intercellular adhesion molecule-1 (ICAM-1), during hypoxia and
      normoxia and hypothesized that salicylate, which inhibits the nuclear factor
      kappaB (NFkappaB), an hypoxia-dependent transmission factor, could reduce this
      expression. METHODS: Human umbilical vein endothelial cells were cultured and
      exposed to normoxia and hypoxia in the presence of lipopolysaccharide (LPS). The
      endothelial cells were thereafter treated with salicylate or indomethacin under
      the same conditions. The surface expression of ICAM-1 was measured by whole cell
      enzyme-linked immunosorbent assay (ELISA) and the NFkappaB expression by Western
      blotting. RESULTS: In the presence of LPS and under hypoxic conditions, the
      endothelial cells produced a 300 +/- 41% increased expression of ICAM-1 compared
      with normoxia. The addition of salicylate (0.02-20 mM) completely inhibited the
      enhanced expression of ICAM-1, the addition of indomethacin at equivalent
      concentrations did not reduce ICAM-1 expression under either condition.
      CONCLUSION: ICAM-1 expression is greatly enhanced by the hypoxic endothelial cell
      in the presence of circulating endotoxin. Pre-treatment with salicylate
      completely abolishes the enhanced expression. The study suggests that salicylate
      administered before cardiopulmonary bypass might protect the heart against
      ischemic/reperfusion injuries and reduce the load of the overall inflammatory
      reaction.

PMID- 9628381
TI  - Sympathetic blockade blunts hypercapnic pulmonary arterial vasoconstriction in
      newborn piglets.
AB  - OBJECTIVE: Hypercapnia has been implicated in the pathophysiology of pulmonary
      hypertensive disease in newborns. However, little has been done to determine how
      its vasoconstrictive actions are mediated. The purpose of this study is to define
      the role of the sympathetic nervous system in modulating the response of the
      newborn pulmonary circulation to hypercapnia. Specifically, we studied the effect
      of sympathetic blockade on mean and pulsatile pulmonary arterial hemodynamics in
      48-h-old, intact, open-chest Yorkshire piglets during hypercapnic ventilation.
      METHODS: All animals were anesthetized and then instrumented for high fidelity
      measurement of pulmonary artery pressure (PAP), flow (PAF), aortic pressure and
      radius of the main pulmonary artery (Rmn). Baseline data were acquired in all
      animals. Control animals (n = 7) were subjected to 30 s intervals of hypercapnia
      (inspired CO2 fraction (FiCO2) = 0.20). Experimental animals (n = 7) were pre
      treated with an intravenous bolus of the adrenergic blocking agent guanethidine
      (20 mg/kg) before being subjected to the hypercapnic stress. Characteristic
      impedance (Zo) and input mean impedance (Zm) were determined through application
      of a Fourier analysis of the PAP and PAF waveforms. The modulus of elasticity
      (Ey) was calculated from Zo and Rmn. Pulmonary vascular resistance (PVR) was
      calculated as (PAP - LAP/PAF). RESULTS: Control animals underwent significant
      increases in PVR (4860 +/- 341 dyne cm s(-5) versus 8090 +/- 387 dyne cm s(-5), P
      < 0.01) and Zm (7215 +/- 495 dyne cm s(-5) versus 10228 +/- 993 dyne cm s(-5), P
      < 0.01) when exposed to hypercapnia. Pre-treatment with guanethidine attenuated
      this response (PVR, 5552 +/- 368 dyne cm s(-5) versus 7105 +/- 611 dyne cm s(-5),
      P = 0.31 and ZM, 7922 +/- 446 dyne cm s(-5) versus 9745 +/- 600 dyne cm s(-5), P
      = 0.31). Characteristic impedance, modulus of elasticity and the radius of the
      main pulmonary artery were unchanged in both groups. CONCLUSIONS: These data
      indicate that vasoconstriction secondary to hypercapnia in the neonatal pulmonary
      arterial circulation occurs at the level of the distal arteriolar bed, rather
      than the more proximal pulmonary arteries. In addition, this response is
      partially modulated by the sympathetic nervous system and may therefore respond
      clinically to manipulation of sympathetic input to the pulmonary arterial
      circulation.

PMID- 9628382
TI  - Successful reoperation for severe left bronchus compression after repair of
      persistent truncus arteriosus with interrupted aortic arch.
AB  - Signs of the left bronchus compression, caused by aneurysmatic dilatation of the
      aortic root with severe aortic regurgitation, occurred 5 months after repair of
      the truncus arteriosus with interrupted aortic arch in an 85-day-old infant. At
      reoperation the dilated ascending aorta was replaced with a 14-mm Dacron tube.
      The aortic valve was replaced with an 18-mm Carbomedics valve. Compression of the
      left bronchus and the right pulmonary artery were released. The right pulmonary
      artery was enlarged with a pericardial patch and the original homograft was
      replaced with a new one. The patient remains in good clinical condition 2 years
      later.

PMID- 9628383
TI  - Primary repair of transposition of the great arteries with interrupted aortic
      arch.
AB  - Primary repair of transposition of the great arteries with interrupted aortic
      arch was performed in a 2 day old neonate weighing 2.1 kg. The repair consisted
      of a direct anastomosis between the ascending and the descending aorta and an
      arterial switch repair without Lecompte procedure because of the side by side
      position of the great arteries and an anomaly of the coronary arteries. A total
      of 28 months after the repair, the patient remains in excellent clinical
      condition.

PMID- 9628384
TI  - Long-term survival after repeated resections of Askin tumor recurrences.
AB  - The case of a 16-year-old boy is reported who underwent surgery for the excision
      of an Askin tumor and has subsequently undergone six excisions of local Askin
      tumor recurrences, with follow-up postoperative chemo- and radiotherapy over a 7
      year period. The patient continues to survive. As far as can be determined, this
      patient appears to be the first reported case of long-term survival after
      repeated resections of local Askin tumor recurrences. It thus may be that
      postoperative chemo- and radiotherapy after repeated excisions of these local
      Askin tumor recurrences plays a role in prolonging survival.

PMID- 9628385
TI  - Dysphagia due to pancreatic pseudocyst with mediastinal extension.
AB  - This case report describes a patient who presented with severe dysphagia, found
      to be due to a large pancreatic pseudocyst extending into the mediastinum. The
      patient was successfully treated by cystgastrostomy.

PMID- 9628386
TI  - Obstructive right ventricular cardiac fibroma in an adult.

PMID- 9628387
TI  - Cardiac papillary fibroelastoma of the mitral valve chordae.
AB  - Papillary fibroelastomas are rare, benign, primary cardiac tumors, usually single
      and small. The neoplasm consists of a leafy, soft excrescence typically located
      on the cardiac valves. Although papillary fibroelastomas are usually an
      asymptomatic incidental finding at autopsy, or during cardiac operation, they are
      occasionally associated with embolic coronary or cerebral symptoms. A case of a
      patient is reported with papillary fibroelastoma of the mitral valve chordae, who
      presented several transitory ischemic attacks characterized by loss of
      conscience, visual bilateral deficit and right emiparesis. Because of their
      potential systemic embolization, we believe that these lesions should be always
      excised.

PMID- 9628388
TI  - Long survival after axillary metastasis from lung cancer.
AB  - Right axillary lymph node metastases was observed 4 months after a right lower
      lobectomy performed for a T2 NO lung adenocarcinoma. After surgical excision and
      subsequent radiotherapy follow-up was uneventful and the patient is still alive
      after a 6-year interval. Such isolated metastases are probably of systemic
      origin.

PMID- 9628389
TI  - Survival after resection of pulmonary metastases: a proposal of number-size (NS)
      score as a prediction.

PMID- 9628390
TI  - Diagnostic algorithm in secondary esophageal strictures.

PMID- 9628391
TI  - Temporary distal occlusion for non-pharmacological preconditioning of harvested
      internal mammary artery grafts.
AB  - Perioperative spasm of the internal mammary artery (IMA) may result in early
      restriction of bypass flow. Therefore, pharmacological pretreatment is usually
      suggested. We present a technique of temporary distal occlusion of the
      transsected IMA using a metal clip. After 1 hour of storage in normal saline
      (SAL) there were significantly better flow rates compared with proximal
      application of a bull-dog clamp. No further increase in flow was noticed after
      submersion of the IMA pedicle in verapamil (VER). This technique easily provides
      sufficient IMA flow at the time of anastomosis, probably due to continuous
      endoluminal dilatation of the IMA by blood pressure, and thus avoids
      pharmacological pretreatment with vasodilators.

PMID- 9628392
TI  - Long-term antibodies after an oral immunization with cholera toxin are
      synthesized in the bone marrow and may play a role in the regulation of memory B
      cell maintenance at systemic and mucosal sites.
AB  - To study the importance of the bone marrow in the long-term antibody response,
      IgG and IgA antitoxin antibody-forming cells were evaluated by ELISPOT in Peyer's
      patches, mesenteric lymph nodes, spleen, lamina propria of the small intestine
      and bone marrow at several times after oral immunization with cholera toxin. The
      mesenteric lymph node was the site having the major frequency of IgG antitoxin
      during the first two weeks after priming, whereas lamina propria was the site
      with a major number of IgA antitoxin antibody-forming cells. However, from 3
      weeks until 10 months after priming, bone marrow became the site with the major
      frequency of IgG, and especially IgA antitoxin antibody-forming cells (without
      taking into account the lamina propria). This result indicates that bone marrow
      was responsible for the long-term antibody response and raises questions
      concerning the mechanisms involved in the maintenance of antibody production. The
      importance of bone marrow as a site of antibody production was great when we
      analysed results as the true contribution of the total number of antitoxin
      antibody-forming cells, taking into account the number of cells recovered from
      each organ. When we analysed the anatomical location of memory B and T cells by
      adoptive transference, we found that cells from mesenteric lymph nodes and spleen
      were able to transfer a strong antibody response to naive syngeneic recipients,
      whereas bone marrow cells transferred a weak antibody response.

PMID- 9628393
TI  - Some new techniques for RNA or DNA analysis of interest for immunologists.
AB  - Technological advances in the field of nucleic acid analysis were the object of a
      recent meeting held in Lisbon. This report presents those techniques that may be
      most useful for immunologists as well as some of their potential applications.
      The topics covered include automation, quantitative PCR and its alternatives,
      oligonucleotide chips, and in situ hybridization and PCR.

PMID- 9628394
TI  - Does a peptide bound to a monoclonal antibody always adopt a unique conformation?
AB  - The conformation of a synthetic undecapeptide derived from the Escherichia coli
      tryptophan synthase beta2 subunit was studied by NMR spectroscopy when bound to a
      monoclonal antibody (mAb 164-2) Fab' fragment directed against the native
      protein. The peptide 1(H-G-R-V-G-I-Y-F-G-M-K)11, peptide 11, was recognized by
      the antibody and its corresponding Fab' fragments with high affinity (K(D) =
      1.1+/-0.2* 10(-8) M). Peptide 11 was labelled with 15N and its structure at the
      binding site of the Fab' 164-2 fragment was studied by isotope-editing
      techniques. 1H-15N heteronuclear spectra indicated the presence of two Fab'
      peptide 11 complexes with two different conformations in slow chemical exchange
      on the chemical shift time scale.

PMID- 9628395
TI  - Nitric oxide downregulates tumour necrosis factor in mRNA in RAW 264.7 cells.
AB  - Nitric oxide (NO) and tumour necrosis factor (TNF) are essential mediators in a
      number of biological processes, including the immune response. TNF stimulates NO
      production via expression of inducible NO synthase (iNOS), with L-arginine being
      the only substrate. Previously, we demonstrated that, inversely, NO inhibits
      lipopolysaccharide (LPS)-induced TNF synthesis. We have now investigated whether
      this reduction of TNF bioactivity is also reflected at the level of TNF mRNA in
      the murine macrophage cell line RAW 264.7. TNF mRNA was quantified by Northern
      analysis using an alpha[33P]dCTP-labelled probe. Cells stimulated with 10
      microg/ml LPS in the absence of L-arginine, in order to prevent endogenous NO
      formation, contained more TNF mRNA than cells supplied with 1 mM L-arginine at 14
      h and 20 h after stimulation. By contrast, no difference was observed at 4 h.
      This time course is compatible with the involvement of iNOS. The half-life of TNF
      mRNA in the presence of NO was roughly half that observed under L-arginine-free
      conditions (41 min versus 77 min, respectively). L-citrulline (1 mM), which has
      been shown to be recycled in RAW 264.7 cells to L-arginine, completely restored
      attenuation of TNF bioactivity and TNF message to control levels obtained with 1
      mM L-arginine. Together, these findings suggest that endogenous NO regulates TNF
      mRNA, mainly by reducing its half-life. In addition, a distinct additional band
      (approximately 1.4 kb) hybridizing with the TNF probe was consistently observed
      in non-stimulated cells. This may correspond to TNF mRNA specifically hydrolysed
      at the AU-rich region, possibly reflecting another control point for TNF
      expression.

PMID- 9628396
TI  - Genetics of immunological tolerance: I. Bidirectional selective breeding of mice
      for oral tolerance.
AB  - The polygenic nature of oral tolerance regulation was elucidated by the method of
      bidirectional selective breeding of mouse strains for tolerance susceptibility
      (TS) and resistance (TR) starting from a genetically heterogeneous population
      achieved by the equilibrated intercrossing of eight inbred mouse strains (A/J,
      DBA/2J, P/J, SWR/J, SJL/J, CBA/J, BALB/cJ and C57BL/6J). Seven days after
      intragastric administration of 5 mg OVA or BSA, mice were intraperitoneally
      immunized with 100 microg of the corresponding antigen. The individual antibody
      titres were measured by haemagglutination. The phenotypes at the highest and
      lowest extremes were selected for assortative mating, avoiding consanguinity. The
      second litter of each mating couple was intraperitoneally immunized only to
      evaluate the immunocompetence of the corresponding generation and to ascertain
      the non-selection of non-responder mice. A normal distribution of agglutinin
      titres ranging from 4 to 14 log2 was observed in the F0 population. In the F12
      generation, TR and TS strains showed highly significant differences for
      agglutinin titres (TR=15.06+/-1.80 and TS=8.35+/-2.44), and IgG responses by
      ELISA. Up to the F12 generation, the mean realized heritability was 0.14+/-0.02.
      The response to the selection was 0.43 log2 and the selection differential 3.10
      log2/generation. A provisional estimation indicated that oral tolerance may be
      influenced by eight or nine independent loci.

PMID- 9628397
TI  - The role of muscle spindles in ankle movement perception in human subjects with
      diabetic neuropathy.
AB  - The objective of this study was to develop a quantitative method to assess muscle
      spindle function. Three groups of subjects were studied: ten young and healthy
      subjects, 15 older subjects with diabetic neuropathy, and 15 age-matched
      controls. All subjects performed an ankle-movement matching task with and without
      muscle vibration. Input from the plantar cutaneous mechanoreceptors was minimized
      by using a foot-clamping device. The younger subjects tracked the movement very
      well, but vibration had a significant effect on their performance (P < 0.001).
      Similar results were seen in the older control subjects, but they were less
      successful in tracking movement and slightly less affected by vibration. The
      neuropathic subjects had the most difficulty tracking, and vibration had only a
      small but still significant effect on their performance. The interaction between
      the group and the vibration effect was highly significant (P < 0.001), indicating
      that the performance of the control subjects changed to a greater degree in the
      presence of vibration than the performance of the subjects with diabetic
      neuropathy. Muscle spindles are the primary receptors that are involved in the
      change in tracking performance when vibration is added during an ankle-movement
      matching task, and we therefore conclude that the procedure described provides a
      quantitative evaluation of muscle spindle function. The results demonstrate that
      diabetic neuropathy degrades muscle sensory function, which may contribute to the
      impaired balance and unsteadiness of gait that has been observed in diabetic
      neuropathy.

PMID- 9628398
TI  - The build-up of anticipatory behaviour. An analysis of the development of gait
      initiation in children.
AB  - This study analyses the anticipatory postural adjustments during the gait
      initiation process in children aged 2.5, 4, 6 and 8 years. In adults,
      anticipation during gait initiation includes a shift in the centre of foot
      pressure (CP) both backwards and towards the stepping foot. Backward displacement
      and the duration of the anticipation phase covary with the gait progression
      velocity reached by the subject at the end of the first step. In the present
      study, the children walked on a force plate that allowed us to calculate the
      acceleration of the centre of mass and the displacements of the CP. The results
      showed three main characteristics of the development of anticipatory behaviour:
      (1) The occurrence of anticipatory displacements of the CP increased
      progressively with age. Systematic backward anticipation was found for all
      children except one of the youngest, whereas the lateral displacement was
      systematically observed later, in the 6-year group; (2) the amplitude of the
      spatial parameters showed a significant increase with age; (3) contrary to the
      adult, the amplitude of the backward shift did not covary with the forthcoming
      velocity in the youngest groups. This covariation became significant at 6 years
      and remained significant at 8 years. The results showed that even if anticipatory
      behaviour was present in 2.5-year-old children it is only later that the child is
      able of more accurate tuning of feedforward control, probably due to better
      control of the overall postural adjustments.

PMID- 9628399
TI  - Opioidergic modulation of spinal reflexes activated by mechanical stimulation of
      the heel in the decerebrated, spinalized rabbit.
AB  - The effects of opioid receptor blockade on reflex responses elicited in medial
      gastrocnemius and semitendinosus motor nerves by controlled mechanical
      stimulation of the skin over the heel have been investigated in decerebrated,
      spinalized rabbits. Pinch forces of 173 mN, 561 mN (light touch), 1642 mN (firm
      pinch) and 4632 mN (firm to painful) were used. In the control state, background
      activity was absent from gastrocnemius motoneurones and low in semitendinosus.
      Pinches of 561 mN and above evoked brisk reflexes in gastrocnemius motoneurones,
      whereas delayed responses (median latency 1 s) were elicited in semitendinosus by
      pinches of 1642 mN and 4632 mN. Intravenous administration of the non-selective
      opioid receptor antagonist (-)-quadazocine (1-781 microg kg(-1)) dose-dependently
      and stereospecifically increased background activity and enhanced reflex
      responses to all pinch strengths in both medial gastrocnemius and semitendinosus
      muscle nerves. Pinches of 173 mN became reflexogenic and higher intensity stimuli
      evoked significantly larger responses than in the control state. These findings
      show that tonic opioidergic inhibition in rabbit spinal cord is wide-spread and
      non-selective, having a powerful influence on transmission of signals to
      motoneurones from high- and low-threshold cutaneous afferents.

PMID- 9628400
TI  - Effect of focal cerebellar lesions on procedural learning in the serial reaction
      time task.
AB  - Prior studies have shown that procedural learning is severely impaired in
      patients with diffuse cerebellar damage (cortical degeneration) as measured by
      the serial reaction time task (SRTT). We hypothesize that focal cerebellar
      lesions can also have lateralized effects on procedural learning. Our objective
      was to assess the effects of focal cerebellar lesions in procedural learning as
      measured by the SRTT. We studied 14 patients with single, unilateral vascular
      lesions in the territory of the posterior-inferior or superior cerebellar artery,
      who were compared with ten age- and sex-matched controls in a one-handed version
      of the SRTT. Patients with lesions at any other level of the brain or posterior
      fossa were excluded by cranial magnetic resonance imaging. Our results show that
      patients do not acquire procedural knowledge when performing the task with the
      hand ipsilateral to the lesion, but show normal learning with the contralateral
      hand. No correlation was found with the side, size, or vascular territory of the
      lesion. We conclude that procedural learning is impaired in hemispheric
      cerebellar lesions and involves only the hand ipsilateral to the lesion, which
      suggests a critical role for the cerebellum and/or crossed cerebellar-prefrontal
      connections in this type of learning.

PMID- 9628401
TI  - Reach to grasp: the response to a simultaneous perturbation of object position
      and size.
AB  - This study assessed the reach to grasp movement and its adaptive response to a
      simultaneous perturbation of object location and size. The aim was to clarify the
      means by which integration between the neural pathways modulating transport and
      manipulation is achieved. Participants (n = 11) were required to reach 30 cm to
      grasp a central illuminated cylinder of either small (0.7 cm) or large (8 cm)
      diameter. For a small percentage of trials (20/100) a visual perturbation was
      introduced unexpectedly at the onset of the reaching action. This consisted of a
      shift of illumination from the central cylinder to a cylinder of differing
      diameter (large in session A; small in session B) that was positioned 20 degrees
      to the left (n = 10 trials) or to the right (n = 10) of the central cylinder. The
      subject was required to grasp the newly illuminated cylinder. Movement duration
      for these "double" (position and size) perturbed trials was much longer than
      those of control trials to the central cylinder (session A: by an average of 250
      ms; session B: 180 ms), and the increased values were much greater than those
      reported previously in "single" perturbation studies where either size or
      location of the object was perturbed. Initial signs of a response to the "double"
      perturbation were seen almost simultaneously in the transport parameter of peak
      arm deceleration and in the manipulation parameter of maximum grip aperture, but
      these changes were not evident until more than 400 ms after movement onset, a
      response onset much later than that found in "single" perturbation studies. It is
      proposed that the visual change resultant from the double perturbation activates
      integration centres that at first gate the flow of information to the parallel
      channels of transport and manipulation. Following processing of this information,
      these centres act to instigate a synchronised and coordinated response in both
      components. These results add support to the existence of neural centres
      dedicated to the integration of parallel neural pathways, and which exercise
      flexibility in the degree to which these components are "coupled" functionally.

PMID- 9628402
TI  - Corrective loops involved in fast aiming movements: effect of task and
      environment.
AB  - In daily living, we continuously interact with our environment. This environment
      is rarely stable and living beings show remarkable adaptive capacities. When we
      reach for an object, it is necessary to localize the position of this object with
      respect to our own body before programming an adequate arm movement. If the
      target remains stable, the programmed movement brings the hand near the target.
      However, what happens when the target suddenly jumps to another position in
      space? The aim of this work was to investigate how rapid aiming movements are
      corrected when the target is displaced close to movement onset. Our results
      reveal that rapid movements can be modified and that the efficiency of trajectory
      amendments vary according to task (directional or direction/amplitude pointings)
      and environment (structured or darkness). We were most interested in the specific
      role played by peripheral and/or central feedback information (efferent copy) in
      the control of aiming movements. The results suggest that the two types of loops
      are complementary in movement regulation. However, their predominance varies
      according to the nature of the task at hand.

PMID- 9628403
TI  - Changes in the symmetry of rapid movements. Effects of velocity and viscosity.
AB  - Five subjects made rapid, discrete elbow flexion movements over different
      distances, against different inertial loads, as well as under distance and load
      combinations that kept movement time constant. The results demonstrated that an
      increase in peak movement velocity was associated with an increase in the
      temporal symmetry ratio of the movement (acceleration time divided by
      deceleration time), as well as with an increase in both agonist electromyographic
      (EMG) burst duration and antagonist EMG latency. Since an increase in peak
      movement velocity is associated with faster agonist muscle shortening, as well as
      with faster stretching of the antagonist muscle, we hypothesize that the velocity
      related changes in movement symmetry can be viewed as, at least partially, a
      consequence of muscle viscosity. Viscosity increasingly resists the shortening
      agonist and assists the lengthening antagonist when movement velocity increases.
      Therefore, the agonist muscles require more time to produce the required impulse,
      while the antagonist muscle can brake the movement in a shorter period of time.
      In order to test the hypothesis that viscosity is responsible for the velocity
      associated changes in the symmetry ratio, we performed a second experiment with
      distance and load combinations identical to those of the first experiment, but
      with different external viscous loads, which resisted the slower and assisted the
      faster movements. The results demonstrated that the movements became more
      symmetrical in the presence of the viscous load. There were also changes in
      agonist duration and antagonist latency. We conclude that changes in the symmetry
      associated with changes in movement velocity may be due to the effects of either
      muscle viscosity or changes in how muscles are activated to account for
      differences in viscous force.

PMID- 9628404
TI  - Spinal application of omega-conotoxin GVIA, an N-type calcium channel antagonist,
      attenuates enhancement of dorsal spinal neuronal responses caused by intra
      articular injection of mustard oil in the rat.
AB  - Administration of the N-type calcium channel antagonist omega-conotoxin GVIA to
      the spinal cord reduces spinal neuronal responses to innocuous and noxious
      pressure applied to the knee, both in rats with normal knees and in rats in which
      a knee inflammation has induced a state of hyperexcitability in spinal neurons
      (Neugebauer et al. 1996, J Neurophysiol 76: 3740-3749). In the present
      experiments we studied whether the development of hyperexcitability of spinal
      neurons induced by intra-articular injection of mustard oil, an excitant of C
      fibres, can be influenced by spinal pretreatment with omega-conotoxin GVIA. In
      anaesthetized rats, responses of wide-dynamic-range neurons were recorded in the
      spinal dorsal horn when standardized stimulation with innocuous and noxious
      pressure was applied to the knee and ankle joints. Injection of mustard oil into
      the knee joint cavity caused an initial neuronal discharge followed by an early
      (peaking at about 15 min) and a late (after 60 min) facilitation of responses to
      innocuous and noxious stimulation of the knee. Responses to ankle stimulation
      showed only the late facilitation. When omega-conotoxin GVIA (20 microl, 1
      microM) was applied into a small trough onto the spinal cord above the recording
      site the responses to articular stimulation were reduced. Furthermore, when
      mustard oil was injected while omega-conotoxin GVIA was on the spinal cord, the
      early increase in the neuronal responses to innocuous pressure on the knee and
      the late increase in responses to noxious pressure on the ankle were
      significantly smaller than those observed in rats not treated with omega
      conotoxin GVIA; the drop in the responses to noxious pressure on the knee was not
      significant. Thus the spinal application of omega-conotoxin GVIA reduced but did
      not completely prevent the fast and slow development of neuronal
      hyperexcitability of spinal cord neurons produced by a prompt and strong
      excitation of afferent C-fibres. This suggests that N-type calcium channels are
      important for the development of spinal cord hyperexcitability.

PMID- 9628406
TI  - Scaling anticipatory postural adjustments dependent on confidence of load
      estimation in a bi-manual whole-body lifting task.
AB  - Anticipatory control of motor output enables fast and fluent execution of
      movement. This applies also to motor tasks in which the performance of movement
      brings about a disturbance to balance that is not completely predictable. For
      example, in bi-manual lifting the pick-up of a load causes a forward shift of the
      centre of mass with consequent disturbance of posture. Anticipatory postural
      adjustments are scaled to the expected magnitude of the perturbation and are
      initiated well before the availability of sensory information characterising the
      full nature of the postural disturbance. However, when the postural disturbance
      unexpectedly changes, the anticipatory adjustment of joint torques is not
      equilibrated and may result in a disturbance to balance. In a previous study, it
      was demonstrated that apart from anticipatory postural adjustments, corrective
      responses after load pick-up are used to further compensate the postural
      disturbance. In this study it was examined whether the central nervous system
      (CNS) assembles a strategy that incorporates both anticipatory control and
      corrective responses, in which the magnitude of the anticipatory postural
      adjustments depends on the perceived level of predictability of the postural
      disturbance. Subjects performed series of lifts in which the magnitude of the
      load was never revealed to the subject. Two boxes equal in size and colour, but
      different in mass (6 and 16 kg), were used. Differences in expectation were
      created by several lifts with the 16-kg load before the 6-kg box was presented.
      It was observed that the number of strong corrective responses (stepping) varied
      with the number of 16-kg trials that formed the prior experience when the final 6
      kg trial was presented. The follow-up question was whether control relied more on
      anticipation in the stepping trials, compared with trials in which such gross
      signs of imbalance were absent. In this study it was shown that subjects when
      stepping (i) exhibited differential anticipatory postural adjustments in
      comparison with 6-kg trials in which expectation was not shaped by preceding 16
      kg trials, and (ii) scaled the anticipatory postural adjustments similar to those
      preceding lift-off of the 16-kg trial preceding it. These findings emphasise the
      programmed nature of the anticipatory postural adjustments and the ability of the
      CNS to selectively tune the anticipatory postural adjustments to stored
      information gained during the previous lift(s).

PMID- 9628405
TI  - Passive properties of neostriatal neurons during potassium conductance blockade.
AB  - Voltage recordings from neostriatal projection neurons were obtained using in
      vitro intracellular techniques before and during K+-conductance blockade. Neurons
      were stained with the biocytin technique. Somatic surface area (AS) was
      determined by both whole-cell recordings in isolated somata and by measuring
      stained somata recorded in slices. Dendritic measurements were done in
      reconstructed neurons. Average determinations of dendritic (AD) and neuronal (AN)
      surface areas coincided with previously reported anatomical data. Thus: As
      approximately 6.5 x 10(-6) cm2; AD approximately 1.9 x 10(-4) cm2; AN
      approximately AD + AS approximately 2 x 10(-4) cm2; AD/AS approximately 30.
      Measurements were done before and after superfusion with K+-conductance blockers
      (K+-blockers). Cells whose neuronal morphology was not obviously distorted by K+
      blockade were chosen for the present study. Electrotonic transients were matched
      to a somatic shunt equivalent cylinder model adjusted with the generalized
      correction factor (Fdga) that constrains the parameters for neuronal anatomy.
      Neuronal input resistance (RN; mean +/- SEM) increased when it was corrected for
      somatic shunt, from 49 +/- 2 Momega (n = 80) to 179 +/- 7 Momega (n = 32). A
      difference was also obtained between the slowest time constant, tau0 = 16 +/- 0.9
      ms (n = 49), and the dendritic membrane time constant, taumD = 33 +/- 1.6 ms (n =
      36). When these electrophysiological measurements were used to calculate AN, the
      value obtained was similar to the anatomical measurements. Combining anatomical
      and electrophysiological data, somatic and dendritic input resistances were
      determined: RD = 182 +/- 7 Momega; Rs (with shunt) = 74 +/- 4 Momega (n = 32).
      The generalized correction factor, Fdga = 0.91 +/- 0.007 (n = 10), implied a
      short effective electrotonic length for dendrites: LD = 0.46 +/- 0.014 (n = 32).
      Saturating concentrations of the K+-blockers tetraethylammonium, Cs+, and Ba2+
      increased RN and induced charging curves well fitted by single exponential
      functions in 56% of neostriatal neurons. Ba2+ greatly decreased the somatic shunt
      (n = 5): (RN = 216 +/- 21 Momega, tau0 = 46 +/- 2 ms, RD = 239 +/- 25 Momega, and
      RS = 3.2 +/- 0.5 Gomega), rendering values similar to those obtained with whole
      cell recordings (e.g., RN approximately 198 Momega, RS approximately 2.62 Gomega)
      (n = 52). Cs+ (n = 5) had less effect on the somatic shunt (RN = 115 +/- 19
      Momega, tau0 = 49 +/- 13 ms, RS = 161 +/- 8 Momega), although dendritic
      conductance was equally blocked (RD = 261 +/- 16 Momega). The Cs+-sensitive
      conductance exhibited inward rectifying properties not displayed by the Ba2+
      sensitive conductance, suggesting that Cs+ preferentially acted upon inward
      rectifier conductances. In contrast, Ba2+ significantly acted upon linear
      conductances making up the somatic shunt. This suggests a differential action of
      different K+-blockers on the somato-dendritic membrane, implying a differential
      distribution of membrane conductances. Another action of K+-blockers, in about
      40% of the cells, was to induce dye and probably electrical coupling between
      neighboring neurons.

PMID- 9628407
TI  - Effects of macrophage migration inhibitory factor and macrophage migration
      stimulatory factor on function and survival of foetal dopaminergic grafts in the
      6-hydroxydopamine rat model of Parkinson's disease.
AB  - Activated microglia play an important role in the rejection of intracerebral
      grafts and the degeneration of axotomized neurones. We studied the effect of
      macrophage migration stimulatory factor (MSF) or macrophage migration inhibitory
      factor (MIF) on allogeneic foetal mesencephalic dopaminergic grafts transplanted
      into the striatum of 6-hydroxydopamine-lesioned rats. Rotation testing revealed a
      significant compensation of lesion-induced motor asymmetry 3 weeks post-grafting
      in animals treated with MIF and vehicle-treated controls compared with pre-graft
      values (Student's t-test, P < or = 0.005) and MSF-treated animals (ANOVA, post
      hoc Fisher PLSD test, P < or = 0.05). The MSF group showed no significant
      compensation. Graft recipients with MIF application (1452.06 +/- 164.32 tyrosine
      hydroxylase-positive ventral mesencephalic cells) and controls (1753.21 +/-
      165.51 tyrosine hydroxylase-positive neurones) displayed good graft survival.
      Animals with MSF application showed a significant reduction of tyrosine
      hydroxylase-positive grafted cells (MSF 570.36 +/- 209.49 cells) and graft
      volumes compared with the MIF and the control group (ANOVA, post hoc Fisher PLSD
      test, P < or = 0.05). The proportional area of microglia was significantly
      reduced in MIF animals compared with control animals (ANOVA, post hoc Fisher PLSD
      test, P < or = 0.001). Activated microglia and macrophages were reduced by half
      in the MIF-treated group compared with MSF animals and controls. We conclude that
      intrastriatal injections of MSF result in impaired function and survival of
      allogeneic ventral mesencephalon (VM) grafts 3 weeks after transplantation. MIF
      can reduce the number of microglia and macrophages in allogeneic foetal VM
      grafts. A reduction of microglia via MIF application did not enhance graft
      function and survival.

PMID- 9628408
TI  - Somatosensory discrimination of shape: prediction of success in normal volunteers
      and parkinsonian patients.
AB  - Tactile discrimination of macrogeometric objects in a two-alternative forced
      choice procedure represents a complex task including somatosensory and higher
      order cognitive processing. The objects for somatosensory discrimination were
      rectangular parallelepipeds that differed in oblongness only. They were presented
      in sequential pairs to 12 normal volunteers and 13 parkinsonian patients. Owing
      to the dichotomy of the task, we calculated estimates of the probability of a
      correct answer by a binomial approach. The probability of a correct answer could
      be calculated on the basis of a logistic model ensuring that the probability
      values lie in the interval [0, 1]. The relationship between the probability of a
      correct answer and the difference in oblongness of the objects could be described
      solely by one coefficient determined by logistic regression. This coefficient
      summarized the effectiveness of the simultaneous and consecutive operations
      inherent in the task and allowed characterization of performances in groups and
      individuals.

PMID- 9628409
TI  - NOS-like immunoreactive neurons express GABA-like immunoreactivity in rabbit and
      rat retinae.
AB  - In rabbit and rat retinae, wholemounted preparations and 40 microm thick
      vibratome sections were processed for nitric oxide synthase (NOS)
      immunoreactivity and consecutive semithin sections were immunostained with anti
      NOS and anti-GABA antisera, respectively. Two types of NOS-labelled amacrine
      cells were identified: type 1 cells with larger somata were intensely stained,
      and type 2 cells with smaller somata were weakly stained. A few displaced
      amacrine cells also showed NOS-like immunoreactivity. All these NOS-like
      immunoreactive neurons also expressed GABA-like immunoreactivity. Thus, nitric
      oxide-containing neurons might constitute a subpopulation of GABAergic neurons in
      rabbit and rat retinae.

PMID- 9628410
TI  - Corticostriatal projections from the somatic motor areas of the frontal cortex in
      the macaque monkey: segregation versus overlap of input zones from the primary
      motor cortex, the supplementary motor area, and the premotor cortex.
AB  - It is an important issue to address the mode of information processing in the
      somatic motor circuit linking the frontal cortex and the basal ganglia. In the
      present study, we investigated the extent to which corticostriatal input zones
      from the primary motor cortex (MI), the supplementary motor area (SMA), and the
      premotor cortex (PM) of the macaque monkey might overlap in the putamen.
      Intracortical microstimulation was performed to map the MI, SMA, and dorsal (PMd)
      and ventral (PMv) divisions of the PM. Then, two different anterograde tracers
      were injected separately into somatotopically corresponding regions of two given
      areas of the MI, SMA, PMd, and PMv. With respect to the PMd and PMv, tracer
      injections were centered on their forelimb representations. Corticostriatal input
      zones from hindlimb, forelimb, and orofacial representations of the MI and SMA
      were, in this order, arranged from dorsal to ventral within the putamen. Dense
      input zones from the MI were located predominantly in the lateral aspect of the
      putamen, whereas those from the SMA were in the medial aspect of the putamen. On
      the other hand, corticostriatal inputs from forelimb representations of the PMd
      and PMv were distributed mainly in the dorsomedial sector of the putamen. Thus,
      the corticostriatal input zones from the MI and SMA were considerably segregated
      though partly overlapped in the mediolateral central aspect of the putamen, while
      the corticostriatal input zone from the PM largely overlapped that from the SMA,
      but not from the MI.

PMID- 9628411
TI  - Fast, anticipatory smooth-pursuit eye movements appear to depend on a short-term
      store.
AB  - Anticipatory smooth pursuit before the expected appearance of a moving target can
      reduce the initial retinal blur caused by the 100-ms delay of visual feedback.
      Humans, though, can only voluntarily generate smooth velocities up to about 5
      degrees/s without a moving target. However, previous experiments have shown that
      repetitive brief presentations of a moving target every few seconds appear to
      charge an internal store, the contents of which can later be released to generate
      higher velocity anticipatory movements. This store's longevity was assessed here
      by repetitively presenting a moving target for 500 ms at different known
      intervals up to 7.2 s. Target motion at 25 degrees/s or 50 degrees/s was tested,
      with presentations in alternate directions or the same direction. Anticipatory
      velocity, measured 100 ms after target onset, decreased with increasing interval
      for all target motion conditions. A decrease was still seen when accurate timing
      cues were given before each presentation, suggesting that the drive for
      anticipatory pursuit is held in a short-term store lasting a few seconds which
      can enhance the low velocities produced by volition alone. The results also
      demonstrate that high-velocity anticipatory pursuit helps to overcome the
      temporal delays in the system and allows target velocity to be matched at an
      earlier time.

PMID- 9628412
TI  - The role of head movements in the control of manual prehension.
AB  - Binocular information has been shown to be important for the programming and
      control of reaching and grasping. But even without binocular vision, people are
      still able to reach out and pick up objects accurately - albeit less efficiently.
      As part of a continuing investigation into the role that monocular cues play in
      visuomotor control, we examined whether or not subjects could use retinal motion
      information, derived from movements of the head, to help program and control
      reaching and grasping movements when binocular vision is denied. Subjects reached
      out in the dark to an illuminated sphere presented at eye-level, under both
      monocular and binocular viewing conditions with their head either free to move or
      restrained. When subjects viewed the display monocularly, they showed fewer on
      line corrections when they were allowed to move their head. No such difference in
      performance was seen when subjects were allowed a full binocular view. This
      study, combined with previous work with neurological patients, confirms that the
      visuomotor system "prefers" to use binocular vision but, when this information is
      not available, can fall back on other monocular depth cues, such as information
      produced by motion of the object (and the scene) on the retina, to help program
      and control manual prehension.

PMID- 9628413
TI  - Phase-dependent electromyographic activity of the lower-limb muscles of a patient
      with clinically complete spinal cord injury during orthotic gait.
AB  - We examined the lower-limb electromyographic (EMG) activity from a patient with
      clinically complete spinal cord injury during orthotic gait. A newly developed
      gait orthosis was used to obtain bipedal locomotion. The surface EMG data during
      the gait together with the biomechanical variables were collected by way of a
      radio EMG system. A cyclic EMG activation pattern corresponding to the gait
      cycles were observed in each of the paralyzed lower-limb muscles during the
      orthotic gait. Although the EMG activation did not seem to contribute toward
      generating the gait, it showed some similarities to that of the infant stepping
      or immature gait. These results might be regarded as one of the indirect pieces
      of evidence that suggest the existence of a spinally originating motor mechanism
      underlying human locomotion.

PMID- 9628414
TI  - Behavioral asymmetries and neurochemical changes after unilateral lesions of
      tuberomammillary nucleus or substantia nigra.
AB  - Previous studies in the rat have shown that the hypothalamic tuberomammillary
      nucleus, the major source of neuronal histamine, is related to mechanisms of
      learning, memory, reinforcement, and functional recovery. These functional
      relationships were found to be partly lateralized. Therefore, we decided to
      analyze whether unilateral ibotenic acid lesions aimed at this brain region would
      acutely lead to asymmetries in open-field behavior, and whether they would affect
      the biogenic amines dopamine and serotonin in the neostriatum, hippocampus, and
      tectum. We compared this manipulation with unilateral 6-hydroxydopamine lesions
      of the substantia nigra pars compacta and with unilateral ibotenic acid lesions
      of the substantia nigra pars reticulata. These lesions were investigated because
      all three brain areas are anatomically linked to the neostriatum, are related to
      the neurotransmitters dopamine and serotonin, and play a role in behavioral
      asymmetry and functional recovery. In support of previous findings, our data show
      that 6-hydroxydopamine lesions of the substantia nigra pars compacta led to an
      ipsiversive asymmetry in turning and scanning. Ibotenic acid lesions of the
      adjacent pars reticulata led to contraversive turning, whereas thigmotactic
      scanning was reduced bilaterally. In contrast, ibotenic acid lesions of the
      tuberomammillary nucleus did not affect turning, but led to an ipsilateral
      asymmetry in scanning. Neurochemically, the 6-hydroxydopamine lesion was mainly
      characterized by the well-known ipsilateral neostriatal dopamine depletion and
      increased residual dopamine activity. In hippocampus and tectum, these
      transmitters were not specifically affected, except for an asymmetry of serotonin
      in the superior colliculus. The ibotenic acid lesions of the pars reticulata did
      not deplete neostriatal dopamine, indicating that they spared the dopaminergic
      output of the substantia nigra. In contrast, they affected dopaminergic and
      serotonergic measures in the colliculi, which may be due to damage of the nigral
      GABAergic projection to this brain area. In animals with unilateral ibotenic acid
      lesions of the tuberomammillary nucleus, several markers of dopaminergic and
      serotonergic activity were increased in the neostriatum, tectum, and hippocampus.
      This effect may have been due to the loss of inhibition otherwise provided by the
      wide-ranging histaminergic output of the tuberomammillary nucleus. These results
      are discussed with respect to the major outputs of the three brain areas, their
      potential impacts on neurotransmitters in their projection sites, and their role
      in behavioral asymmetry.

PMID- 9628415
TI  - The collicular code of saccade direction depends on the roll orientation of the
      head relative to gravity.
AB  - This paper investigates the influence of static head tilt on the relation between
      activity in the motor layers of the superior colliculus (mSC) and saccadic
      oculomotor output. Based on single-unit recordings and electrical
      microstimulation in awake rhesus monkeys, we report that head roll changes the
      direction of the saccade vector generated by the mSC, with respect to a head
      fixed coordinate system. Typically, the vector rotates in a direction that is
      opposite to the head roll direction. This rotation exceeds the amount of ocular
      counterroll that is observed as a result of difference in static head roll
      positions. We find that the mSC works in an oculocentric coordinate system that
      is biased in the direction of gravity. It is argued that the modification is a
      result of processes that occur downstream of or parallel to the mSC.

PMID- 9628416
TI  - Tail and eye movements evoked by electrical microstimulation of the optic tectum
      in goldfish.
AB  - This work studies the tail and eye co-ordinated movements evoked by the focal
      electrical stimulation of the tectum in goldfish. The aim of the study is to
      understand better those tectal sites and mechanisms that either remain
      functionally unaltered or are adaptively modified across vertebrates. Stimulation
      was applied in various tectal zones, and the characteristics of evoked tail and
      eye movements were examined as a function of the stimulation site over tectal
      surface and the stimulus parameters. Two types of response were electrically
      evoked: the former turned the body and the eyes contraversively towards the
      source of natural stimulus; the second produced initial ipsiversive turning of
      the body and eyes, followed by several tail beats. Evoking one or other response
      depended on both the site and parameters of stimulation, and responses were
      interpreted as orienting- and escape-like, respectively. Depending on the
      stimulation site, four different zones in the tectum were distinguished: in the
      medial zone the stimulus elicited eye and tail movements whose size increased
      with the distance to the rostral pole. The stimulation of the antero-medial zone
      evoked contraversive or ipsiversive eye saccades but tail movements were similar,
      irrespective of eye movements. Stimulation within the extreme antero-medial zone
      evoked convergent eye movements, and tail displacements turning the body either
      ipsiversively or contraversively. Stimulation of the posterior zone often evoked
      complex tail movements and pure horizontal eye saccades. Both orienting- and
      escape-like responses were also dependent on the stimulus parameters. The
      relationships between stimulus parameters and tail- and eye-orienting movement
      characteristics suggest that the velocity and duration might be encoded in
      different aspects of the tectal activity. Current strength also modified the
      number of tail beats that appeared during escape-like response. In conclusion,
      the present data suggest the involvement of the optic tectum not only in
      orienting but also in escape responses and that movements of eye and tail
      mediating such responses depend on the tectal active locus together with its
      level of activity.

PMID- 9628417
TI  - Dipolar sources of the early scalp somatosensory evoked potentials to upper limb
      stimulation. Effect of increasing stimulus rates.
AB  - Brain electrical source analysis (BESA) of the scalp electroencephalographic
      activity is well adapted to distinguish neighbouring cerebral generators
      precisely. Therefore, we performed dipolar source modelling in scalp medium nerve
      somatosensory evoked potentials (SEPs) recorded at 1.5-Hz stimulation rate, where
      all the early components should be identifiable. We built a four-dipole model,
      which was issued from the grand average, and applied it also to recordings from
      single individuals. Our model included a dipole at the base of the skull and
      three other perirolandic dipoles. The first of the latter dipoles was
      tangentially oriented and was active at the same latencies as the N20/P20
      potential and, with opposite polarity, the P24/N24 response. The second
      perirolandic dipole showed an initial peak of activity slightly earlier than that
      of the N20/P20 dipolar source and, later, it was active at the same latency as
      the central P22 potential. Lastly, the third perirolandic dipole explaining the
      fronto-central N30 potential scalp distribution was constantly more posterior
      than the first one. In order to evaluate the effect of an increasing repetition
      frequency on the activity of SEP dipolar sources, we applied the model built from
      1.5-Hz SEPs to traces recorded at 3-Hz and 10-Hz repetition rates. We found that
      the 10-Hz stimulus frequency reduced selectively the later of the two activity
      phases of the first perirolandic dipole. The decrement in strength of this
      dipolar source can be explained if we assume that: (a) the later activity of the
      first perirolandic dipole can represent the inhibitory phase of a "primary
      response"; (b) two different clusters of cells generate the opposite activities
      of the tangential perirolandic dipole. An additional finding in our model was
      that two different perirolandic dipoles contribute to the centro-parietal N20
      potential generation.

PMID- 9628418
TI  - Target anticipation and impairment of smooth pursuit eye movements in
      schizophrenia.
AB  - A reduced gain of smooth pursuit eye velocity has frequently been reported in
      schizophrenic patients. With respect to predictable stimuli, this could be due to
      a deficit in predicting the target path. To determine this contribution to smooth
      pursuit eye movement performance, we analyzed the ocular smooth pursuit response
      to a sinusoidally moving target that was suddenly stopped after some cycles of
      regular movement. Horizontal eye movements were recorded with infrared reflection
      oculography in a group of 17 schizophrenic in-patients and 16 age-matched healthy
      subjects for controls. The patients exhibited a reduced gain of smooth pursuit
      velocity, but phase lag was not different from the control group. After the
      unpredictable stop of target movement, predictive sinusoidal smooth pursuit was
      maintained for 150 to 200 ms in both groups. The resulting maximal position and
      velocity error was larger in the patient group. In conclusion, schizophrenic
      patients were able to generate a normal anticipatory component of smooth pursuit
      and to switch it off in response to external demands. They showed, however, an
      increased velocity of anticipatory pursuit, which might be used to compensate for
      the primary deficit of smooth pursuit velocity frequently found in
      schizophrenics.

PMID- 9628419
TI  - Timing variability of repetitive saccadic eye movements.
AB  - We assessed the suitability of using the Wing and Kristofferson model for timing
      repetitive motor responses to analyse timing variability during repetitive
      saccadic eye movements. The model decomposes total timing variability (TV) into a
      central timing component (CV) and a peripheral motor delay component (MV). Eight
      normal subjects made voluntary horizontal saccades, in darkness, in synchrony
      with a regular auditory metronome. After 20 saccades had been produced, the
      metronome was switched off and subjects continued responding at the same
      frequency until 31 further saccades had been made. Inter-saccade intervals (ISIs)
      from the unpaced phase were used to calculate TV, CV and MV. Three different
      target intervals, paced by auditory cues, were used - 496 ms, 752 ms and 1000 ms.
      In the paced phase, subjects' ISIs closely matched the auditory cue intervals. In
      the unpaced phase, subjects were clearly able to respond at three different
      frequencies. As predicted by the Wing and Kristofferson model, the durations of
      successive ISIs tended to be negatively correlated. As expected, TV and CV
      increased with increasing ISI. Contrary to the expectation of the model that MV
      would remain constant, we found that it increased with increasing interval. Our
      results do not conclusively demonstrate the validity of applying the Wing and
      Kristofferson model to the analysis of timing variability during repetitive
      saccadic eye movements. However, comparison with previous studies shows that, at
      least in normal subjects, it is equally valid to apply the model to the analysis
      of repetitive saccadic eye movements as it is to apply it to the analysis of data
      from other effectors.

PMID- 9628420
TI  - Developmental changes in NMDA receptor-mediated visual activity in the rat
      superior colliculus, and the effect of dark rearing.
AB  - N-methyl-D-aspartate (NMDA) receptor-mediated activity is considered important
      for experience-dependent plasticity in the developing visual system. We
      investigated the influence of age and experience on the role of NMDA receptors in
      the visual transmission in the superficial grey layer of the superior colliculus
      (SGS) of the superior colliculus, where, in the adult, NMDA receptors mediate a
      substantial part of the visual response. In normally reared (postnatal day 14,
      P14, to adult) rats, visual responses were challenged with NMDA receptor
      selective iontophoretic applications of the antagonist D-2-amino-5
      phosphonovalerate (AP5). After eye opening (at P14), there was a significant
      increase in the number of neurones whose visual responses were reduced during AP5
      ejection, which peaked at P22 (85%; n = 21), and then declined to adult levels
      (66%; n = 47) at P25. The mean reduction of the response (from control levels) by
      AP5 was similar at all ages (approximately 40%). Dark rearing had striking
      effects on the role of NMDA receptors in visual transmission, especially when
      comparisons were made between age-matched subjects greater than P25. In these
      subjects, AP5 ejection reduced the visual responses of all neurones studied. In
      addition, AP5 ejection caused a significantly larger reduction of visual
      responses in dark-reared rats (mean reduction 62 +/- 4; n = 29) compared with age
      matched controls (mean reduction 44 +/- 8; n = 23). The D,L-alpha-amino-3-hydroxy
      5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX) reduced the visual responses of every neurone
      studied and there were no age- or experience-dependent effects. We conclude that
      NMDA receptors, but not AMPA receptors, assume greater importance for visual
      transmission in the SGS of dark-reared rats.

PMID- 9628421
TI  - Changes in excitability of the flexor carpi radialis H-reflex following tactile
      stimulation of the index fingertip.
AB  - Adequate stimulation of cutaneous afferents from the fingertip evokes a short
      latency inhibition followed by a long-lasting excitation in human flexor carpi
      radialis (FCR) motoneurones. Changes in excitability of flexor motoneurones were
      investigated in 11 subjects by means of the H-reflex conditioning technique. The
      index fingertip, immobilised on a flat table, was stimulated by a small probe
      mounted on an electromagnetic vibrator. Contact time and tactile perception
      threshold (PT) were monitored throughout the experiment. In all subjects, tactile
      stimulation of the skin covering the index pulp, with 10 ms long square pulses,
      at an intensity of 2-2.5 PT, produced an inhibition starting at a conditioning
      test interval of 15 ms and lasting about 2 ms. This was followed by a powerful
      facilitation lasting more than 10 ms. Excitation appeared just at tactile
      threshold, whereas threshold for inhibition was about 2 PT. Similar effects were
      observed after mechanical stimulation of the skin covering the dorsal aspect of
      the index, close to the nail. Local anaesthesia of the finger pulp drastically
      reduced both the inhibition and the facilitation of FCR H-reflex. By contrast,
      electrical stimulation of the index digital nerves, by means of ring electrodes,
      was always ineffective in modifying the excitability of the FCR H-reflex. It is
      proposed that inhibition and excitation of FCR H-reflex are caused by activation
      of oligosynaptic pathways fed by cutaneous afferents; however, it cannot be
      excluded that joint receptors and primary endings of small hand muscles may
      contribute in part to the late excitation. The pathways described might play an
      essential role in modulation and control of exploratory movements and object
      manipulation, actions that need tactile information to regulate muscle force.

PMID- 9628422
TI  - Attention in action or obstruction of movement? A kinematic analysis of avoidance
      behavior in prehension.
AB  - Obstacle avoidance strategies are of two basic but interrelated types: moving
      around an obstacle to that body parts do not come too close, and slowing down. In
      reaching-to-grasp, avoidance may involve the transport component, the grasp
      formation component, or both. There has been little research that has directly
      examined obstacle avoidance strategies during reaches-to-grasp. Several recent
      reports describe experiments in which reaches-to-grasp were made when nontarget
      objects were present in the workspace. The effects of these nontargets were
      interpreted as being due to their distracting effects rather than their
      obstructing effects. The results of these studies are reinterpreted as being due
      to the non-target's obstructing effects. The obstacle interpretation is more
      parsimonious and better predicts the pattern of results than the distractor
      interpretation. Predictions of the obstacle interpretation were examined in an
      experiment in which participants were required to reach to grasp a target in the
      presence of another object in various locations. The results were exactly in line
      with the interpretation of the object as an obstacle and the data show how grasp
      and transport movements are subtly adjusted so as to avoid potential obstacles.
      It is proposed that people move so as not to bring body parts within a minimum
      preferred distance from nontarget objects within the workspace. What constitutes
      the preferred distance in a particular context appears to depend upon the speed
      of movement and a variety of psychological factors related to the cost that a
      person attaches to a collision.

PMID- 9628423
TI  - A comparison of curvatures of left and right hand movements in a simple pointing
      task.
AB  - Human arm movements towards visual targets are remarkably reproducible in several
      tasks and conditions. Various authors have reported that trajectories of
      unconstrained point-to-point movements are slightly curved, smooth and have bell
      shaped velocity profiles. The hand paths of such movements show small - but
      significant - curvatures throughout the workspace. The cause of these curvatures
      is still obscure. Traditionally this curvature is explained as the result of an
      optimisation process or is ascribed to mechanical or dynamic properties of the
      effector system. Recently, however, it has been suggested that these curvatures
      are due at least partly, to the visual misperception of straight lines. To
      evaluate the latter hypothesis, we compared unconstrained, self-paced point-to
      point movements that subjects made with their right and left hand. We assume that
      the visual misperception may depend on the position in the workspace, subject,
      etc. but not on the hand used to make the movement. Therefore we argue that if
      curvature is caused by a visual misperception of straight lines, curvatures
      should be the same for movements made with the left and right hand. Our
      experiments cast strong doubt on the hypothesis that curvatures are the result of
      a visual distortion, because curvatures of the left hand trajectories, mirrored
      in the mid-sagittal plane, are found to be accurately described by trajectories
      of the right hand. Estimates of the effect of visual distortion on movement
      curvature show that, if present, this effect is very small compared with other
      sources that contribute to movement curvature. We found that curvatures depend
      strongly on the subject and on the direction and distance of the movement.
      Curvatures do not seem to be caused purely by the dynamic properties of the arm,
      since curvatures do not change significantly with increasing movement velocity.
      Therefore, we conclude that curvatures reflect an inherent property of the
      control of multi-joint arm movements.

PMID- 9628424
TI  - Motor learning in the "podokinetic" system and its role in spatial orientation
      during locomotion.
AB  - The present study characterizes a previously reported adaptive phenomenon in a
      somatosensory-motor system involved in directional control of locomotor
      trajectory through foot contact with the floor. We call this the "podokinetic"
      (PK) system. Podokinetic adaptation was induced in six subjects by stepping in
      place over the axis of a horizontally rotating disc over a range of disc angular
      velocities (11.25-90 degrees/s) and durations (7.5-60 min). After adaptation,
      subjects were blindfolded and attempted to step in-place on the floor without
      turning. Instead they all rotated relative to space. The rate of the "podokinetic
      afterrotation" (PKAR) was linearly related to stimulus amplitude up to 45
      degrees/s, and the ratio of initial PKAR velocity to that of the adaptive
      stimulus was approximately 1:3. PKAR exhibited exponential decay, which was
      composed of "short-" and "long-term" components with "discharging" time constants
      on the order of 6-12 min and 1-2 h, respectively. The effect of stimulus duration
      on PKAR revealed a "charging" time constant that approximated that of the short
      term component. A significant suppression of PKAR occurred during the 1 st min of
      the postadaptive response, suggesting functional interaction between the PK and
      vestibular systems during the period of vestibular stimulation. During PKAR
      subjects perceived no self-rotation, indicating that perception as well as
      locomotor control of spatial orientation were remodeled by adaptation of the PK
      system.

PMID- 9628425
TI  - The preparation, execution and suppression of copied movements in the human
      brain.
AB  - We used positron emission tomography (PET) to measure movement set-related
      changes in regional cerebral blood flow (rCBF) when human subjects were asked to
      copy hand movements. Movement set-related activity in the brain is thought to
      reflect the processes of movement selection, preparation and inhibition. Four
      conditions were used. In the first condition, prepare and execute (PE), the hand
      stimulus to be copied was shown to subjects 3 s before an auditory "go"-cue
      instructed subjects to execute the movement; a large part of the scanning time
      was therefore spent in preparing to move. In the immediate execution condition
      (E), the hand stimulus and the go cue were presented simultaneously. The prepare
      only condition (P) was similar to PE, except subjects only prepared to make the
      movement and did not actually execute any movement when they heard the auditory
      go-cue. The same stimuli were presented in a baseline condition (B), but the
      subjects were instructed to neither prepare nor execute movements. There were 5
      principle findings: (1) In contrast to a previous study of human set-related
      activity in which movements were instructed by an arbitrary pattern of LEDs,
      preparing to make a copied movement causes rCBF changes in area 44 in posterior
      Broca's area; (2) set-related activity can be recorded in the cerebellar
      hemispheres and midline; (3) we confirmed that the supramarginal gyrus has a
      general role in preparing movements - there was more rCBF in the P than the E
      condition; (4) the cerebellar nuclei and the basal ganglia may be particularly
      involved in the initiation and execution of a planned movement; these regions
      were more active in the PE condition than the P condition; (5) the ventrolateral
      prefrontal cortex and a left anterior cingulate area are part of a distributed
      system involved in the suppression of a motor response; these areas were
      significantly more active in the P than the PE condition.

PMID- 9628426
TI  - Hippocampal mossy fiber sprouting is not impaired in brain-derived neurotrophic
      factor-deficient mice.
AB  - In human temporal lobe epilepsy, a loss of hilar neurons followed by the
      sprouting of recurrent mossy fiber collaterals and the reinnervation of free
      synaptic sites on granule cell dendrites are discussed as possible mechanisms
      underlying hippocampal hyperexcitability. Dentate granule cells have been shown
      to upregulate brain-derived neurotrophic factor (BDNF) as well as TrkB, the high
      affinity receptor for BDNF, in response to limbic seizures. This raised the
      possibility that BDNF is an important factor in hippocampal mossy fiber
      sprouting. Here we have used slice cultures of hippocampus, in which mossy fibers
      sprout and form a supragranular plexus in response to granule cell
      deafferentation, and have compared cultures from early postnatal BDNF-deficient
      mice and wild-type mice. We demonstrate that there is sprouting of supragranular
      mossy fibers in cultured slices from both BDNF knock-out and wild-type mice. We
      conclude that BDNF is not an essential factor for mossy fiber sprouting. However,
      our data do not exclude a role for BDNF in mossy fiber sprouting in wild-type
      mice, as compensatory mechanisms might have become effective in the mutant.

PMID- 9628427
TI  - Recombinant human erythropoietin in children with cancer.

PMID- 9628429
TI  - Deficient in vitro megakaryocytopoiesis and decreased in vivo platelet turnover
      in children and young adults with chronic thrombocytopenia.
AB  - PURPOSE: Chronic thrombocytopenia is uncommon in children and frequently thought
      to be secondary to chronic idiopathic thrombocytopenic purpura (ITP), which is
      considered an immune disorder. However, not all children with chronic ITP respond
      to immunosuppressive therapy. Platelet survival and megakaryocyte growth were
      studied to determine if there is a failure of platelet production in children
      with chronic thrombocytopenia who carry a presumptive diagnosis of chronic ITP.
      PATIENTS AND METHODS: In vitro megakaryocyte growth using a plasma clot system
      and in vivo survival of 111In-labeled autologous platelets were studied in seven
      patients (aged 2 days to 17 years at diagnosis; aged 2 to 28 years at time of
      megakaryocyte study) with chronic isolated thrombocytopenia (range 1,000 to
      130,000/microl). RESULTS: All seven patients exhibited elevated platelet
      associated immunoglobulin G early in the course of their disease and showed
      normal marrow morphology with normal numbers of morphologically typical
      megakaryocytes on initial marrow biopsy. Occasional dysplastic-appearing
      megakaryocytes were noted in three of the seven patients at diagnosis and all
      patients were noted to have dysplastic megakaryocytes, reduced megakaryocytes, or
      both during follow-up (range 5 to 16 years). Either morphologic or karyotypic
      abnormalities indicative of myelodysplasia subsequently developed in three
      patients. No patient exhibited any significant megakaryocyte colony growth under
      basal conditions. In one patient, megakaryocytic colonies significantly increased
      when grown in the presence of serum from aplastic patients and growth factors
      (granulocyte-macrophage colony-simulating factor, interleukin-3, and interleukin
      6). Erythroid colony growth was markedly deficient in four of five patients
      studied and myeloid colonies were normal in two of three patients studied. Five
      of the seven patients underwent platelet survival studies. Platelet survival was
      < 6 days in the 4 patients with platelet counts < 100,000/microl (range 2 to
      60,000/microl; survival range 92 to 137 hours) and was normal in the patient
      whose platelet count was > 100,000/microl (platelets 132,000/microl; survival 253
      hours). All five patients had either overtly low or inappropriately low platelet
      turnovers (range 100 to 1423 platelets/microl per hour; normal range 1200 to 1600
      platelets/microl per hour). The patient with the lowest platelet count and
      platelet turnover had previously undergone a splenectomy without benefit.
      CONCLUSIONS: Megakaryocyte dysfunction resulting in subnormal production of
      platelets may play a significant role in the thrombocytopenia noted in some
      patients who have an isolated thrombocytopenia and a clinical picture that
      suggests ITP. Determination of platelet turnover may help to identify these
      patients. These data suggest the presence of a stem cell defect which may
      progress to myelodysplasia or overt marrow failure in these patients.

PMID- 9628428
TI  - Prognostic significance of TEL/AML1 fusion transcript in childhood B-precursor
      acute lymphoblastic leukemia.
AB  - PURPOSE: A retrospective study was conducted to investigate the prognostic
      significance of TEL/AML1 fusion resulting from a cryptic t(12;21) in Japanese
      patients with childhood B-precursor acute lymphoblastic leukemia (ALL). MATERIALS
      AND METHODS: Leukemic samples from 144 children with newly diagnosed ALL (104
      with CD10-positive B-precursor ALL, 11 with CD10-negative B-precursor ALL, 5 with
      B-ALL, and 24 with T-ALL) were analyzed by reverse-transcription polymerase chain
      reaction. RESULTS: The frequency of patients with TEL/AML1 was 16% (23 of 144)
      and all patients with TEL/AML1 also had CD10-positive B-precursor ALL. TEL/AML1
      was not found in any samples from the patients with T-ALL, B-ALL, or CD10
      negative B-precursor ALL. Among patients with CD10-positive B-precursor ALL, age,
      initial white blood cell count, and immunophenotype did not differ with TEL/AML1
      positivity, although the patients were predominantly male (p < 0.01). Clinical
      outcomes of 94 patients treated with recent protocols were analyzed. Five of the
      21 (23.8%) patients with TEL/AML1 relapsed and 4 of these relapsed > 24 months
      after diagnosis. Although the overall 5-year survival rate was better among
      patients with TEL/AML1 fusion transcript than among those without it (87.3 +/-
      8.7% versus 75.9 +/- 5.8%, respectively), the 5-year disease-free survival (DFS)
      rates of patients with TEL/AML1 fusion transcript and those without it were
      similar (64.0 +/- 13.5% versus 69.1 +/- 6.3%, respectively). However, for 57
      patients treated with the latest intensive protocol, the 4-year DFS rate was much
      higher for the patients with TEL/AML1 fusion transcript than for those without it
      (100.0% v.s. 69.6 +/- 8.4%, respectively, p = 0.1472). CONCLUSIONS: This study
      confirmed that TEL/AML1 gene fusion is the most common genetic event in pediatric
      ALL in Japan and is restricted to CD10-positive B-precursor ALL. Moreover, it was
      associated with an improved survival rate among patients treated with intensive
      therapy. Therefore, these data suggest that the patients with TEL/AML1 may not
      necessarily be candidates for less aggressive treatment.

PMID- 9628431
TI  - Heterogeneity of immune markers in hemophagocytic lymphohistiocytosis:
      comparative study of 9 familial and 14 familial inheritance-unproved cases.
AB  - PURPOSE: Although immune dysfunction is suspected in patients with hemophagocytic
      lymphohistiocytosis (HLH), the difference between immune dysfunction in patients
      with familial erythrophagocytic lymphohistiocytosis (FEL) and familial
      inheritance-unproved lymphohistiocytosis (FIU) remains unknown. The aim of this
      study was to determine useful markers to distinguish patients with FEL from those
      with FIU. PATIENTS AND METHODS: Clinical features and laboratory findings,
      especially natural killer (NK) cell activity and the relative frequencies of
      peripheral blood mononuclear cell (PBMC) subsets, and serum levels of interferon
      gamma and soluble interleukin-2 receptor were compared in 9 patients with FEL and
      14 age-matched patients with FIU. Twenty-seven healthy infants served as
      controls. The treatment and outcome were also compared for patients with FEL and
      FIU. RESULTS: Comparison between patients with FEL and FIU revealed significantly
      lower NK activity in those with FEL (p = 0.03) but failed to show any significant
      differences in PBMC subsets, except that the percentage of CD3+ T cells was
      higher in patients with FEL (p = 0.02). CD4- and CD8-dominant phenotypes were
      characteristic findings in both groups of patients, although increased CD19+ B
      cells were restricted to patients with FIU. NK activity was deficient (< 5%) in
      four of the seven patients with FEL tested but in only one of eight patients with
      FIU. By comparison to values for age-matched controls, the percentages of CD3+,
      CD3+DR+ and CD45RO+ PBMCs in patients with FEL were significantly high (p < 0.05)
      and those of CD19+ and CD45RA+ subsets were lower than normal. Among patients
      with FIU, PBMC subsets included significantly reduced CD3+, CD4+, CD45RA+, and
      CD4+CD45RA+. In this small series, the outcome of patients with FEL and FIU
      treated with chemotherapy was not significantly different at the time of
      evaluation. CONCLUSIONS: These results indicate considerable immune heterogeneity
      among patients with HLH younger than 2 years. Although NK activity was useful but
      not diagnostic, determination of PBMC subsets and patterns of cytokine expression
      was not helpful in distinguishing patients with FEL from those with FIU,
      suggesting that the immune responses characteristic of these diseases may reflect
      different triggering factors, including viruses. The impact of this immune
      heterogeneity on patients' outcome remains to be determined.

PMID- 9628430
TI  - BRa (HPA-5b) incompatibility may cause thrombocytopenia in neonates of mothers
      with immune thrombocytopenic purpura.
AB  - PURPOSE: The association of anti-Br(a) immunoglobulin G (IgG) platelet
      alloantibodies with the development of thrombocytopenia in neonates of mothers
      with autoimmune thrombocytopenic purpura (ITP) is reported. METHODS: Between
      March 1994 and July 1997, 28 consecutive pregnant women with ITP seen at New York
      Hospital were screened for platelet-reactive antiglycoprotein (glycoprotein [GP]
      IIb/IIIa, Ib/IX, and Ia/IIa) antibodies. RESULTS: The sera from 6 of these 28
      women contained IgG alloantibodies to GP Ia/IIa directed against the Br(a) (HPA
      5b) antigen. Only three families each had at least one Br(a)+ and at least one
      Br(a)- infant. Platelet typing in these families revealed that the mothers were
      Br(b/b) (Br(a)-) and the fathers were Br(a/b) (Br(a)+). Platelet counts <
      100,000/microl occurred only in 2 of the 3 infants who were Br(a)+. The platelet
      counts were significantly lower in the three Bra+ infants compared to the five
      Br(a)- infants (p = 0.038). CONCLUSION: Platelet alloimmunization with anti-Br(a)
      can cause neonatal thrombocytopenia in infants of mothers with ITP. Platelet
      antibody testing in the pregnant women with ITP is recommended.

PMID- 9628432
TI  - Septicemia and septic shock in pediatric patients: 140 consecutive cases on a
      pediatric hematology-oncology service.
AB  - PURPOSE: This report describes the incidence of septic shock in pediatric
      hematology-oncology patients with positive blood cultures and investigates
      parameters of potential use in early diagnosis of gram-negative (GN) bacteremia
      and septic shock. PATIENTS: In a 12-month period, 140 consecutive episodes of
      septicemia (135 bacterial and 5 fungal) were seen in 100 patients. The absolute
      neutrophil count (ANC) was > 500/microl in 89 episodes (65%). RESULTS: Septic
      shock developed in patients with positive blood cultures with an overall
      incidence of approximately 19%. Of the 12 bacteremic patients who required
      transfer to the intensive care unit, 83% had a GN isolate recovered. The
      incidence of septic shock was not significantly lower in the group of patients
      with ANC > 500/microl. Low serum bicarbonate correlated with GN infection in
      patients with bacteremia. CONCLUSIONS: GN organisms were the major cause of
      septic shock in a group of pediatric hematology-oncology patients with positive
      blood cultures although they were recovered less frequently than gram-positive
      organisms. In our study, non-neutropenic patients with indwelling catheters were
      at approximately the same risk for GN shock as neutropenic patients. Monitoring
      blood carbon dioxide content may be useful in the early diagnosis of GN
      infection.

PMID- 9628433
TI  - Multicolor flow-cytometric, morphologic, and clonogenic analysis of marrow CD10
      positive cells in children with leukemia in remission or nonmalignant diseases.
AB  - PURPOSE: To characterize nonleukemic CD10-positive cells in the marrows of
      children with leukemia in remission or benign conditions. PATIENTS AND METHODS:
      Seventeen children with acute leukemia in complete remission, 12 with solid
      tumors, and 17 with benign blood diseases were included in this study. Bone
      marrow cells were analyzed by multicolor flow-cytometry and polymerase chain
      reaction (PCR) to detect immunoglobulin gene rearrangement. The CD10-positive
      cells were purely sorted and examined by light microscopy and single cell
      hemopoietic progenitor assay. RESULTS: In patients with acute leukemia, CD10
      positive cells were present in higher proportion after completion of therapy than
      during chemotherapy. They were also higher in the patients of preschool age than
      in the older age group with benign blood diseases and solid tumors. These CD10
      positive cells were morphologically compatible with immature lymphocytes but some
      blast-like cells also occurred in this population. Most CD10-positive cells
      coexpressed CD19 and HLA-DR, although only 10 to 30% coexpressed CD20 and CD34.
      Although some CD10-positive cells expressed CD34, they did not make any colonies.
      PCR analysis did not show monoclonal bands in CD10-positive bone marrow cells in
      any patients in remission. CONCLUSION: Marrow CD10-positive cells possess
      immature B-lymphocyte phenotype and are present in higher proportion in the
      marrows of children with acute leukemia in continuous complete remission after
      completion of therapy and children of preschool age than school-age children with
      benign diseases or solid tumors without marrow involvement. The clonality of
      these cells was excluded by PCR, which is a distinct point from CD10-positive ALL
      blasts.

PMID- 9628434
TI  - Intensive alternating drug pairs after remission induction for treatment of
      infants with acute lymphoblastic leukemia: A Pediatric Oncology Group Pilot
      Study.
AB  - PURPOSE: Infants with acute lymphoblastic leukemia (ALL) often enter remission;
      however, they have a high rate of relapse. To prevent relapse, infants' tolerance
      of and benefits from early intensive rotating drug pairs as part of therapy were
      studied. METHODS: After prednisone, vincristine, asparaginase, and daunorubicin
      induction, 12 intensive treatments (ABACABACABAC) were administered in 30 weeks:
      A, intermediate dose methotrexate (MTX) and intermediate dose mercaptopurine
      (MP); B, cytosine arabinoside (Ara-C) and daunorubicin (DNR); C, Ara-C and
      teniposide (VM-26). Triple intrathecal chemotherapy (Ara-C, MTX, and
      hydrocortisone) was administered for central nervous system prophylaxis.
      Continuation therapy consisted of weekly MTX and daily MP for a total of 130
      weeks of continuous complete remission. RESULTS: Thirty-three infants (1 year old
      or younger) with newly diagnosed ALL were treated. Two infants did not respond to
      induction, 1 died from sepsis during continuation, 1 received a bone marrow
      transplant, and 24 relapsed. Median time to relapse was 39 weeks. The event-free
      survival rate at 5 years was 17% (standard error +/- 7.7%). The most significant
      toxicities occurred during intensification and included fever-neutropenia and
      bacterial sepsis. CONCLUSION: Although early intensive rotating therapy is
      tolerable, the relapse-free survival rate remains poor for infants treated with
      the schedule on this protocol.

PMID- 9628436
TI  - Bone mineral density in young adult survivors of childhood cancer.
AB  - PURPOSE: Childhood cancer and its treatment can affect normal bone accretion. In
      this study, bone mineral density (BMD) in young adult survivors of childhood
      cancer is assessed to determine what cancer-related factors, patient
      characteristics, or treatment-related complications correlate with reductions in
      BMD. PATIENTS AND METHODS: The study population consisted of 40 (24 women) long
      term survivors of childhood cancer treated at the Memorial Sloan-Kettering Cancer
      Center for a solid tumor (n = 16), lymphoma (n = 14), or acute leukemia (n = 10)
      at a mean age of 12.7 +/- 0.96 years and evaluated at a mean age of 25.8 +/- 0.7
      years. Dual energy X-ray absorptiometry was used to determine BMD of the lumbar
      spine, femoral neck, and total body and single photon absorptiometry was used to
      determine BMD of the distal radius. RESULTS: The mean BMD standard deviation
      score (SDS) for the patients was significantly reduced compared to controls at
      the distal radius (-1.57 +/- 0.18, p = 0.0001), femoral neck (-0.68 +/- 0.20, p =
      0.00014), and total body (-0.33 +/- 0.15, p = 0.03) but not at the lumbar spine (
      0.22 +/- 0.22, p = 0.33). Univariate analysis revealed that gonadal dysfunction
      (i.e., estrogen or testosterone insufficiency) (p = 0.018) was the only variable
      that correlated with a reduced BMD. CONCLUSION: Young adult survivors of
      childhood cancer have reduced BMD. Because age at study coincides with the normal
      age of attainment of peak bone mass and peak bone mass is a major determinant of
      BMD later in life, many of these patients are at increased risk for osteoporosis
      and fractures.

PMID- 9628438
TI  - Neonatal alloimmune thrombocytopenia associated with maternal anti-HLA antibody:
      a case report.
AB  - PURPOSE: Although neonatal alloimmune thrombocytopenia (NAIT) due to maternal
      sensitization to human platelet antigens is well described, the role of maternal
      anti-human lymphocyte antigen (HLA) antibodies in NAIT is not yet firmly
      established. PATIENT: A 31-week-old girl born prematurely to a G2POA1 mother was
      noted to have thrombocytopenia which lasted 18 days without any evidence of
      infection. MATERIALS AND METHODS: Platelet-associated IgG, anti-platelet
      antibody, and platelet PL(A1) antigen typing were determined using a commercial
      solid-phase red cell adherent test. Antibodies to platelet glycoproteins human
      platelet antigen (HPA) 1 to 5 were determined using a commercial ELISA. Anti-HLA
      antibodies were assayed using a standard lymphocytotoxicity test. Activities and
      IgG subclass of anti-HLA antibodies in plasma of the mother and other postpartum
      mothers were measured using purified HLA antigens in an enzyme linked
      immunoassay. RESULTS: Both mother and infant were positive for HPA-1 (PL(A1))
      antigens. The mother's HLA phenotype was A3, A31, B7, B27. The level of platelet
      associated IgG was not increased on maternal platelets; however, increased
      platelet-associated IgG was detected on the infant's platelets. Antibodies to
      platelet glycoproteins HPA1 to 5 were not detectable in the maternal plasma.
      Maternal serum was positive for anti-HLA antibodies, which reacted to 23 of 27
      panel cells. The presence of HLA antibodies was confirmed by enzyme-linked
      immunoassay. Of note, the maternal antibodies reacted positively to the infant's
      platelets and anti-IgG anti-HLA antibodies were detected in the serum sample from
      the infant collected at birth. When the activity and IgG subclass of the maternal
      anti-HLA antibodies were compared with those of other mothers known to have high
      anti-HLA antibody activity, no differences were noted. CONCLUSION: This report
      documents a patient with neonatal thrombocytopenia induced by maternal IgG anti
      HLA antibody. Neither activity nor IgG subclass could explain the occurrence of
      NAIT. The factors that contribute to NAIT induced by maternal anti-HLA antibodies
      remain to be identified.

PMID- 9628435
TI  - Reduced bone mineral density in long-term survivors of childhood acute
      lymphoblastic leukemia.
AB  - PURPOSE: Osteoporosis and pathologic fractures are occasionally found in patients
      with childhood acute lymphoblastic leukemia (ALL). This study was performed to
      determine the degree of possible osteopenia in long-term survivors of childhood
      ALL. PATIENTS AND METHODS: Lumbar spine (L2-L4) and femoral neck bone mineral
      densities (BMDs) (g/cm2) were measured in 29 survivors (aged 12 to 30 years,
      median 17) of childhood ALL 2 to 20 (median 8) years after discontinuation of
      chemotherapy. These results were compared with those from 273 healthy controls
      and expressed as a percentage of the age- and sex-matched control values (mean +/
      standard deviation). RESULTS: Lumbar and femoral BMDs were significantly reduced
      in survivors of childhood ALL. Particularly, male gender (lumbar: 91.7 +/- 10.4%,
      p = 0.008; femoral: 91.9 +/- 11.3%, p = 0.005) and a history of cranial
      irradiation (lumbar: 93.0 +/- 8.9%, p = 0.005; femoral: 94.4 +/- 13.3%, p = 0.03)
      were associated with low lumbar and femoral BMDs. CONCLUSIONS: The detected
      deficit in bone density in survivors of childhood ALL may predispose these
      patients to osteoporotic fractures later in adulthood. A follow-up of BMD in
      survivors of childhood ALL should facilitate the identification of patients who
      would require specific therapeutic interventions to prevent further decrease of
      their skeletal mass and preserve their BMD.

PMID- 9628439
TI  - Matched unrelated human umbilical cord blood transplantation for X-linked
      adrenoleukodystrophy.
AB  - PURPOSE: This report evaluates engraftment, immunologic reconstitution, and sera
      very-long-chain fatty acid levels after matched unrelated human umbilical cord
      blood transplantation (HUCBT) for adrenoleukodystrophy (ALD). PATIENT AND
      METHODS: A child with X-linked ALD underwent matched unrelated HUCBT and
      administration of granulocyte colony stimulating factor in combination with
      erythropoietin. RESULTS: Engraftment was complete and stable, with 100%
      chimerism. Natural killer cell numbers and function were normal more than 3
      months after HUCBT. T cell numbers normalized more than 9 months after HUCBT but
      T cell mitogenic response remained subnormal. Thirteen months after
      transplantation, the child is in very good clinical condition with normalization
      of his sera very-long-chain fatty acid levels. CONCLUSION: Unrelated cord blood
      transplantation may provide a good source of stem cells for patients with ALD
      when a matched sibling is not available.

PMID- 9628442
TI  - Spontaneous resolution of myelofibrosis and pancytopenia followed by the
      development of acute myeloid leukemia with an extramedullary mass.
AB  - PURPOSE: Spontaneous resolution of myelofibrosis is extremely rare. A patient
      with myelofibrosis and pancytopenia that spontaneously resolved with subsequent
      development of acute myelomonocytic leukemia and an extramedullary mass of the
      ovary is described. PATIENT AND METHODS: A 2-year-old girl had severe
      pancytopenia and myelofibrosis without signs of myeloid metaplasia. The patient
      was transfused with packed red blood cells and platelets and monitored. RESULTS:
      The pancytopenia and myelofibrosis resolved spontaneously within 1 month after
      initial presentation and her blood counts normalized. The patient developed a
      chloroma of the ovary and acute myelomonocytic leukemia 13 months later and
      eventually died from disease. CONCLUSIONS: This patient initially had acute
      myelofibrosis which was most likely secondary to occult acute myelomonocytic
      leukemia. The transfusions may have been a contributing factor in the spontaneous
      remission.

PMID- 9628440
TI  - Disseminated strongyloidiasis in a child with lymphoblastic lymphoma.
AB  - PURPOSE: This report describes a case of disseminated strongyloidiasis in a child
      receiving chemotherapy for T-cell lymphoblastic lymphoma. PATIENT AND METHODS: A
      10-year-old boy became severely ill with disseminated strongyloidiasis 4 weeks
      after starting chemotherapy for T-cell lymphoblastic lymphoma. He responded to
      treatment with supportive care, antibiotics, and albendazole but required
      ivermectin to eradicate the strongyloides infection. CONCLUSION: Disseminated
      strongyloidiasis is a severe, life-threatening complication of Strongyloides
      stercoralis infection that can occur in patients on immunosuppressive therapy,
      particularly when this therapy includes corticosteriods. In endemic areas,
      screening patients due to undergo immunosuppressive treatment and appropriate
      antistrongyloides treatment may be life saving. Ivermectin is the treatment of
      choice.

PMID- 9628437
TI  - Severe bleeding tendency in a patient with Bernard-Soulier syndrome associated
      with a homozygous single base pair deletion in the gene coding for the human
      platelet glycoprotein Ibalpha.
AB  - PURPOSE: The genetic basis of Bernard-Soulier syndrome (BSS) was studied to
      clarify a relationship between severe clinical manifestations and gene
      abnormality. PATIENT AND METHODS: A patient with BSS had a severe bleeding
      tendency that was sometimes life threatening. Flow cytometric analysis of the
      patient's and normal control platelets was performed to study which glycoprotein
      (GP) was impaired in glycoprotein Ib/V/IX complex. The genes encoding GPIbalpha
      from the patient's and control genomic DNA were amplified and directly sequenced.
      RESULTS: Flow cytometric analysis revealed a defect of GPIbalpha on the surface
      of the patient's platelets. A homozygous single base pair deletion was identified
      in seven repeats of adenine at positions 1932 to 1938 in the GPIbalpha gene. This
      mutation, which has been previously reported, results in a frameshift and
      predicts a premature stop codon leading to a truncated peptide that cannot fix on
      the platelet membrane. CONCLUSION: This patient's severe clinical phenotype would
      be explained by this mutation in the GPIbalpha gene.

PMID- 9628441
TI  - Identical cytogenetic clones and clonal evolution in pediatric monozygotic twins
      with acute myeloid leukemia: presymptomatic disease detection by interphase
      fluorescence in situ hybridization and review of the literature.
AB  - PURPOSE: Observation of identical acquired genetic changes in infant monozygotic
      (MZG) twins with acute leukemia has provided strong evidence for in utero twin
      twin transfusion as the cause of concordance. Documentation of similar phenomenon
      in older MZG twins offers insight into the latency period for leukemia and may
      provide the opportunity for presymptomatic disease detection in one twin. DESIGN:
      The literature describing leukemia in MZG twins is reviewed and the results of
      classical and molecular cytogenetic studies of one pair of MZG twins at 3 and 4
      years with acute nonlymphocytic leukemia-FAB type M1 are reported. RESULTS: The
      twins studied had cytogenetically identical neoplastic clones with identical
      clonal evolution. Retrospective fluorescence in situ hybridization studies
      demonstrated the presence of the abnormal clone in the asymptomatic twin at the
      time of bone marrow transplant of the first twin. CONCLUSIONS: These observations
      support in utero twin-twin transfer as the origin of leukemic clones in pediatric
      and infant leukemia, demonstrate that clonal evolution of a leukemic clone may
      occur years before onset of overt disease, and indicate that knowledge of
      acquired genetic change(s) in one twin may provide markers to assess disease in
      the asymptomatic twin.

PMID- 9628443
TI  - Abdominal recurrence of osteogenic sarcoma: a case report.
AB  - PURPOSE: Nonpulmonary metastases from osteogenic sarcoma are rare. A patient had
      a localized osteogenic sarcoma of the left femur which recurred in the abdomen, a
      previously unreported metastatic site. PATIENT AND METHODS: An 18-year-old boy
      was treated for osteosarcoma. He had abdominal pain, vomiting, weight loss, and
      symptoms of intestinal obstruction at the time of relapse. RESULTS: The patient
      had diffuse widespread intraabdominal osteogenic sarcoma as the only site of
      initial recurrence. Abdominal computerized tomography revealed ascites and
      calcified masses on the hepatic and peritoneal surfaces. Laparoscopic
      visualization of the abdomen showed hemorrhagic ascites and multiple calcified
      tumor on the peritoneum, diaphragm, and liver. A biopsy of a representative
      lesion confirmed the diagnosis of osteogenic sarcoma. The patient died from
      progressive disease. CONCLUSION: As the initial treatment for patients with
      osteogenic sarcoma is intensified, the pattern of metastases may change. Unusual
      sites of recurrence such as in this patient may become more prevalent. A clinical
      presentation of an acute abdomen in a patient previously treated for osteogenic
      sarcoma should prompt suspicion of intraabdominal recurrence.

PMID- 9628445
TI  - The emerging role of low-molecular-weight heparins in cardiology practice.
      Introduction.

PMID- 9628444
TI  - Hepatocellular carcinoma in children associated with Gardner syndrome or familial
      adenomatous polyposis.
AB  - PURPOSE: Gardner syndrome, a variant of familial adenomatous polyposis, is
      characterized by colonic polyps that undergo malignant change and benign and
      malignant extracolonic lesions. Tumors frequently associated with Gardner
      syndrome include carcinoma of the ampulla of Vater, papillary carcinoma of the
      thyroid, and, in children, hepatoblastoma. The childhood malignancies often
      precede the appearance of other manifestations by several years. PATIENTS AND
      METHODS: Two patients are described. Gardner syndrome was diagnosed in a 15-year
      old girl with fibrolamellar hepatocellular carcinoma after desmoid tumors and
      colonic polyposis developed. Classic hepatocellular carcinoma was also diagnosed
      in a 9 1/2-year-old boy with familial adenomatous polyposis. RESULTS: In patient
      1, the diagnosis of fibrolamellar hepatocellular carcinoma preceded the diagnosis
      of Gardner syndrome by almost 2 years. The diagnosis was confirmed by identifying
      a germline mutation of the adenomatous polyposis coli (APC) gene. This is the
      first patient reported with fibrolamellar hepatocellular carcinoma associated
      with Gardner syndrome. Patient 2 had a strong family history of familial
      adenomatous polyposis but no manifestations of Gardner syndrome. He was not
      tested for the APC mutation. The current literature and previously reported cases
      of hepatocellular carcinoma in patients with Gardner syndrome or familial
      adenomatous polyposis are reviewed. CONCLUSIONS: Because hepatocellular carcinoma
      is uncommon in the pediatric and adolescent population, it is important to
      consider the possibility of Gardner syndrome or familial adenomatous polyposis in
      these patients.

PMID- 9628446
TI  - Pharmacology of the low-molecular-weight heparins.
AB  - Unfractionated heparin (UFH) is widely used to both treat and prevent venous
      thromboembolism. More recently, UFH has been used to prevent death and myocardial
      infarction in patients with unstable angina or acute myocardial infarction and
      acute occlusion in those undergoing percutaneous coronary revascularization.
      However, its poor bioavailability (when administered in low doses
      subcutaneously), its mechanism of clearance, and its short half-life make its
      anticoagulant activity difficult to predict and maintain. To overcome these
      limitations, low-molecular-weight heparins (LMWHs) have been developed that have
      greater bioavailability and a longer half-life in plasma. Because LMWHs provide
      more predictable anticoagulant activity compared with subcutaneous UFH, it is not
      necessary to monitor the activated partial thromboplastin time during treatment.
      These newer agents are as effective as UFH in the prophylaxis and treatment of
      thromboembolic and cardiac disorders and, by allowing shorter hospital stays, are
      more cost effective. Thus LMWHs offer clear pharmacokinetic advantages over UFH.
      More studies are needed to determine the extent to which clinically available
      LMWHs can be used in place of UFH.

PMID- 9628447
TI  - Low-molecular-weight heparin for the treatment of venous thromboembolism.
AB  - Unfractionated heparin (UFH) binds to several plasma, platelet, and endothelial
      proteins, producing a highly variable anticoagulant response. For this reason,
      frequent anticoagulation monitoring and dosage adjustment are necessary during
      UFH administration. In contrast, low-molecular-weight heparins (LMWHs) exhibit
      less protein binding and provide more predictable anticoagulation with reduced
      need for patient monitoring and dosage adjustment. Therefore, LMWHs are
      potentially useful for anticoagulation therapy on an outpatient basis. Several
      recent clinical trials have compared LMWHs (administered primarily on an
      outpatient basis) and UFH for the treatment of venous thromboembolism. These
      trials have indicated that LMWHs possess efficacy and safety characteristics
      similar to intravenous heparin but are easier to administer. LMWH preparations
      vary considerably in their methods of preparation and pharmacological properties,
      and the relative efficacies of these various LMWHs remain to be determined by
      direct comparisons in randomized clinical trials.

PMID- 9628448
TI  - New therapies for unstable angina and non-Q-wave myocardial infarction: recent
      clinical trials.
AB  - Thrombosis after the rupture of an atherosclerotic plaque often precipitates the
      acute coronary syndromes of unstable angina and myocardial infarction. The
      combination of aspirin and heparin has been shown to reduce the occurrence of
      both symptomatic and asymptomatic ("silent") ischemia, myocardial infarction, and
      death in patients with these syndromes. However, heparin and aspirin each have
      significant limitations as antithrombotic drugs. Additionally, coagulation
      abnormalities may persist for several months after an acute ischemic event, and
      long-term anticoagulation may be beneficial. Because of the need for frequent
      anticoagulation monitoring and dosage adjustment, the use of heparin is limited
      to short-term treatment during the acute in-hospital phase. Recently several
      novel antithrombotic treatments have been developed. The benefits of direct
      thrombin inhibitors, platelet fibrinogen receptor antagonists, and low-molecular
      weight heparins in the treatment of acute coronary syndromes have been
      demonstrated in randomized clinical trials.

PMID- 9628449
TI  - TIMI 11B. Enoxaparin versus unfractionated heparin for unstable angina or non-Q
      wave myocardial infarction: a double-blind, placebo-controlled, parallel-group,
      multicenter trial. Rationale, study design, and methods. Thrombolysis in
      Myocardial Infarction (TIMI) 11B Trial Investigators.
AB  - Continuous intravenous (i.v.) heparin administered in the acute period after
      unstable coronary artery disease reduces the likelihood and severity of
      subsequent ischemic events. However, reactivation of the thrombotic process may
      occur when heparin therapy is withdrawn. Low-molecular-weight heparin provides
      more reliable anticoagulation and less need for patient monitoring and dosage
      adjustment than standard unfractionated heparin (UFH) and therefore is well
      suited for long-term anticoagulation on an outpatient basis. TIMI 11B is a
      randomized, double-blind, placebo-controlled clinical trial designed to compare
      the strategy of combined short-term and long-term administration of the low
      molecular-weight heparin enoxaparin for unstable angina/non-Q-wave myocardial
      infarction versus the standard strategy of UFH administration only during the
      acute phase. Patients are randomized to receive either enoxaparin (30 mg i.v.
      bolus followed by subcutaneous (s.c.) injections of 1.0 mg/kg every 12 hours) or
      UFH (70 U/kg bolus followed by an infusion of 15 U/kg per hour, titrated to an
      activated partial thromboplastin time of 1.5 to 2.5 times control). Infusion of
      i.v. UFH or placebo continues for a minimum of 72 hours. S.c. weight-adjusted
      enoxaparin or placebo continues until hospital discharge or day 8, whichever
      comes first, at which time the long-term phase of the study begins. Patients
      randomized to receive enoxaparin in the acute phase receive fixed-dose s.c.
      enoxaparin (60 mg every 12 hours for patients > or =65 kg, 40 mg every 12 hours
      for patients <65 kg). Patients randomized to receive UFH in the acute phase
      receive s.c. placebo injections during the chronic phase. The primary efficacy
      endpoint is the sum, through day 43, of the occurrence of death, nonfatal
      myocardial infarction not present at enrollment, or severe recurrent ischemia
      requiring urgent revascularization. The primary safety endpoint is the occurrence
      of either major bleeding or other serious adverse events.

PMID- 9628450
TI  - Mechanisms of arterial thrombosis: foundation for therapy.
AB  - Intravascular thrombus often occurs when the rupture or fissure of an
      atherosclerotic plaque exposes procoagulant elements lying below the plaque
      surface. This process of plaque rupture is the result both of passive mechanical
      forces and an active cell-mediated mechanism. Recently a number of investigators
      have developed imaging technologies based on magnetic resonance to characterize
      atherosclerotic lesions or the use of radioactively labeled platelets to
      dynamically visualize clot formation and lysis in vivo. These methods may permit
      early detection of developing thrombus, improve selection of treatment, and allow
      direct monitoring of the progression of antithrombotic therapy.

PMID- 9628452
TI  - Antibodies to chondroitin sulfate C: a new detection assay and correlations with
      neurological diseases.
AB  - Antibodies to chondroitin sulfate C (ChS C) have been previously associated with
      sensory axonal neuropathy. Investigation of these antibodies has, however, been
      limited by the lack of a sensitive and reliable test for their detection. We
      developed a new enzyme-linked immunoassorbent assay (ELISA), where biotinylated
      ChS C was made to adhere to avidin-coated microwells. The new ELISA showed a much
      greater sensitivity than other currently available ELISAs for detection of anti
      ChS C antibodies. A total of 480 sera (466 patients and 14 normal volunteers)
      were tested at increasing dilutions for anti-ChS C antibody activity. Normal
      subjects had IgM anti-ChS C antibody titers of up to 3,200 and mildly elevated
      titers of 6,400 were seen in a variety of diseases. Eleven patients had titers of
      12,800 or higher. These included seven patients with sensory axonal neuropathy,
      three with amyotrophic lateral sclerosis and one with corticobasal ganglionic
      degeneration. These studies indicate that anti-ChS antibodies do occur in
      patients with axonal sensory neuropathy, but are not limited to that disease.

PMID- 9628451
TI  - Sulfoglucuronosyl glycolipids as putative antigens for autoimmune inner ear
      disease.
AB  - Autoimmune inner ear disease is diagnosed based on clinical history of
      fluctuating but progressive sensorineural hearing loss (SNHL) with or without
      vestibular symptoms occurring over weeks to months. An initial response to
      steroids or immunosuppressive drugs usually reverses the hearing loss. In search
      of specific diagnostic and therapeutic markers for autoimmune inner ear diseases,
      we investigated serum anti-glycolipid antibody activities in these patients by
      two different methods, HPTLC-immunoblotting and ELISA. We found that 37 out of 74
      patients of clinically diagnosed autoimmune inner ear disease (30 of
      sensorineural hearing loss (SNHL) (group I), 14 of vestibular symptoms only
      (group II), 30 of Menieres symptoms (with both hearing loss and vestibular
      symptoms) (group III)) showed positive anti-sulfoglucuronosyl lactosaminyl
      paragloboside (SGLPG) antibody titers (p < 0.001). On the other hand, anti
      sulfoglucuronosyl paragloboside (SGPG) titers were not elevated in these
      conditions. In contrast, only 3 out of 56 pathological control and 2 out of 28
      healthy volunteers had measurable anti-SGLPG antibody titers. We further analyzed
      the localization of SGLPG in the auditory pathway and found that the antigens
      existed exclusively in inner ear and the eighth nerve, but not in pons,
      cerebellum, nor cerebrum. We conclude that the anti-SGLPG antibody represents a
      novel diagnostic marker for autoimmune inner ear disease and may participate in
      the pathogenesis of this disease.

PMID- 9628453
TI  - Gonadal hormones influence the immune response to PLP 139-151 and the clinical
      course of relapsing experimental autoimmune encephalomyelitis.
AB  - Females have an increased incidence of multiple sclerosis (2:1). This gender
      dimorphism can be studied effectively using a murine model of relapsing
      experimental autoimmune encephalomyelitis (R-EAE). We demonstrated previously
      that male SJL mice immunized with proteolipid protein (PLP) peptide 139-151
      developed an initial episode of paralysis, but failed to relapse. In the present
      study, clinical EAE relapses were induced by orchidectomy. Relapses in castrated
      mice were accompanied by an influx of activated CD4+, Th1 cells into the CNS
      which were absent in sham mice. Our data suggests an important regulatory role
      for androgens on the immune response to PLP 139-151 and the clinical course of R
      EAE.

PMID- 9628454
TI  - T-cell responses to myelin basic protein in normal and MBP-deficient mice.
AB  - BALB/c mice are resistant to the development of experimental autoimmune
      encephalomyelitis (EAE) after immunization with myelin basic protein (MBP).
      Previous studies of BALB/c mice suggest that MBP-specific T-cells can eventually
      be cloned from these mice, although they are either initially present in very low
      frequencies or are functionally anergic. To determine what role endogenous MBP
      expression plays in shaping the BALB/c T-cell repertoire, MBP-deficient BALB/c
      mice were constructed by breeding the shiverer (shi/shi) mutation onto the BALB/c
      background. These mice lack all conventional isoforms of MBP due to a deletion of
      MBP exons 3-7. Studies of the MBP-directed response of these mice suggest that
      endogenous MBP expression is directly responsible for EAE resistance in BALB/c
      mice, by quantitatively affecting expression of the T-cell repertoire. In
      contrast to wild-type BALB/c T-cells, uncloned T-cells from BALB/c shi/shi mice
      immunized with MBP proliferate in vitro to MBP and MBP peptides 59-76 and 89-101
      and are able to induce severe EAE upon transfer to BALB/c recipients expressing
      MBP.

PMID- 9628455
TI  - HLA allele distribution distinguishes sporadic inclusion body myositis from
      hereditary inclusion body myopathies.
AB  - We studied the HLA class II associations in patients with sporadic inclusion body
      myositis (s-IBM) and hereditary inclusion body myopathies (h-IBM) and attempted
      to distinguish these myopathies on the basis of HLA allele assignments. Forty
      five patients, 30 with s-IBM and 15 with h-IBM, underwent HLA class II allele
      specific typing using polymerase chain reaction sequence-specific primers for 71
      alleles contained in the DRbeta1, DRbeta3-5, and DQbeta1 loci. In s-IBM, we found
      a high (up to 77%) frequency of DRbeta1*0301, DRbeta3*0101 (or DRbeta3*0202) and
      DQbeta1*0201 alleles. No significant association with alleles in the DR and DQ
      haplotypes was found among the 15 h-IBM patients. The strong association of
      prominent alleles with s-IBM, but not h-IBM, suggests that s-IBM is a distinct
      disorder with an immunogenetic background that differs from h-IBM.

PMID- 9628456
TI  - Matrix metalloproteinases and tissue inhibitors of metalloproteinases in viral
      meningitis: upregulation of MMP-9 and TIMP-1 in cerebrospinal fluid.
AB  - A hallmark of viral meningitis is the invasion of monocytes, lymphocytes and, in
      the initial phase of the disease, neutrophils into the subarachnoidal space. By
      their degradation of different macromolecular components in the extracellular
      connective tissue, matrix metalloproteinases (MMPs) may be essential for the
      breakdown of the vessel wall in the meninges and the choroid plexus. In this
      study, the occurrence of MMP-1, MMP-2, MMP-3 and MMP-9 and the two tissue
      inhibitors of metalloproteinases, TIMP-1 and TIMP-2, was monitored in the
      cerebrospinal fluid (CSF) from patients with viral meningitis. Of the
      proteinases, MMP-9 was found in 13 of 39 (33%) patients, but not in controls; the
      levels being correlated with the neutrophil cell number in CSF. The CSF
      concentration of TIMP-1 was increased three-fold compared to the control group
      (median 233 ng/ml; range 9.4-1252.5 ng/ml) and was correlated to the levels of
      total protein in CSF. Of the other MMPs and TIMPs assayed, MMP-2 and TIMP-2 were
      constitutively expressed and not upregulated in viral meningitis. High levels of
      MMP-9 and MMP-2, as measured by ELISA, was associated with high proteolytic
      activity detected in CSF by zymography. In conclusion, invasion of the leukocytes
      into the CSF compartment in viral meningitis may involve MMP-9, its proteolytic
      effect likely being controlled by expression of TIMP-1.

PMID- 9628457
TI  - Depletion of radiosensitive leukocytes exacerbates the heart sympathetic
      denervation and parasitism in experimental Chagas' disease in rats.
AB  - The acute phase of the Trypanosoma cruzi infection induces damage of the heart
      sympathetic nerve terminals in rats. The participation of the radiosensitive
      leukocytes in this process was assessed in young rats submitted to gamma
      irradiation 1 day before infection with T. cruzi, Y strain. Gamma irradiation
      increased the heart noradrenergic denervation evaluated at day 12 of infection by
      histochemical and electron-microscopic methods. The presence of numerous
      macrophages with ultrastructural features of activation and a significant rise in
      the myocardial parasitism suggest the involvement of radioresistant macrophages
      or parasite factors, or both, on the damage of the nerve terminals.

PMID- 9628458
TI  - In vivo treatment with anti-alpha4 integrin suppresses clinical and pathological
      evidence of Borna disease virus infection.
AB  - Borna disease virus (BDV) infection of the rat brain induces a severe T
      lymphocyte mediated inflammatory response that parallels the course of clinical
      Borna disease. In other models of CNS inflammation, the recruitment of T
      lymphocytes from the circulation to sites of inflammation is believed to be
      directed, in part, by the cellular adhesion molecules alpha4 beta1 integrin
      (expressed on T-lymphocytes) and its ligand VCAM-1 (expressed on blood brain
      barrier endothelium). Since BDV-specific T-lymphocytes are known to express the
      alpha4 beta1 integrin, we examined the effect of in vivo treatment with an anti
      alpha4 integrin monoclonal antibody (GG5/3) on the development of BDV-specific
      encephalitis and Borna disease. Here, we report that the inhibition of alpha4
      integrin provided significant clinical benefit in slowing the progression of
      Borna disease. Antibody treatment greatly reduced the immune cell infiltrates in
      the CNS of BDV-infected animals, but we found that this inhibition of the immune
      response did not result in enhanced viral levels.

PMID- 9628459
TI  - Diminished monocytic HLA-DR expression and ex vivo cytokine secretion capacity in
      patients with glioblastoma: effect of tumor extirpation.
AB  - Severe immunodysregulation on lymphocyte level has been described in patients
      with glioblastoma and is likely involved into its unfavorable prognosis. Although
      the major importance of monocytic cells for immunoregulation is well established,
      only very limited data exist regarding the monocyte status in glioblastoma
      patients. Here we demonstrate a markedly diminished monocytic HLA-DR expression
      and ex vivo cytokine secretion capacity (TNF-alpha, IL-1beta, IL-10) as signs for
      monocyte deactivation in glioblastoma patients but not in patients with
      astrocytoma. As known in immunocompromised patients from other reasons, monocyte
      deactivation indicate global immunodepression associated with an enhanced risk of
      infectious complications. Interestingly, tumor resection resulted in partial
      recovery from the monocytic deactivation. This suggests that the glioblastoma
      itself contributed to this phenomenon. However, IL-10 and the active forms of
      transforming growth factor-beta2 and -beta1, which are produced by glioblastoma
      cells and known to inhibit monocyte function, were not detectable in plasma in
      our patients. Moreover, low levels of the adrenocorticotropic hormone and
      cortisol excluded hypothalamo-pituitary-adrenal axis involvement. So, further
      investigations are necessary to clarify the mechanism. The demonstrated severe
      glioblastoma-associated monocytic deactivation may contribute to its unfavorable
      prognosis. Therefore, monocytes may represent target cells for new adjuvant
      immunotherapies in glioblastoma.

PMID- 9628460
TI  - T cell recognition of myelin proteolipid protein and myelin proteolipid protein
      peptides in the peripheral blood of multiple sclerosis and control subjects.
AB  - Myelin proteolipid protein (PLP) is a prime candidate autoantigen for multiple
      sclerosis. In order to define potential immunodominant epitopes, T cell lines
      (TCL) from the peripheral blood of HLA-DR 15(2) MS patients were established
      which responded to the intact molecule of PLP. These TCL were then tested in
      individual proliferation assays with a variety of PLP peptides spanning most of
      the PLP molecule. Multiple peptides were recognized by TCL from the MS
      population, with more than one peptide often recognized by lines from the same
      individual. Three immunodominant peptides were identified which were recognized
      by the majority of MS patients. Estimated frequency analyses were then performed
      on the peripheral blood of HLA-DR15(2)-positive MS and control subjects using TCL
      initiated by the three immunodominant peptides, 40-60, 95-117, and 185-206. TCL
      from HLA-DR15 MS subjects recognized peptide 95-117 significantly more often than
      TCL from control subjects.

PMID- 9628461
TI  - Costimulatory CD80 (B7-1) and CD86 (B7-2) on cerebrospinal fluid cells in
      multiple sclerosis.
AB  - The costimulatory CD80 and CD86 molecules were measured by flow cytometry on
      cerebrospinal fluid (CSF) and blood lymphocytes from patients with possible first
      attacks of multiple sclerosis (MS, n = 25), clinically definite MS (n = 16), and
      noninflammatory neurological disease control subjects (n = 30). In patients with
      demyelinating diseases more CSF B cells expressed CD80 than in control subjects
      whereas the expression of CD86 by T cells in CSF was low in patients with
      demyelinating disease and highly variable in the control subjects. In patients
      with possible first attacks of MS the expression pattern of CD80 and CD86
      differed significantly between patients with or without intrathecal synthesis of
      IgG. Increased expression of the CD80 molecule on CSF B cells may be of
      importance in the pathogenesis of MS. In contrast, CSF T cell expression of CD86
      may be associated with protection from MS.

PMID- 9628462
TI  - Desferrioxamine suppresses experimental allergic encephalomyelitis induced by MBP
      in SJL mice.
AB  - Data from several studies indicate that free radicals have a pathogenic role in
      experimental allergic encephalomyelitis (EAE). Iron can contribute to free
      radical damage by catalyzing the formation of hydroxyl radical, inducing
      secondary initiation of lipid peroxidation and by promoting the oxidation of
      proteins. The iron chelator, desferrioxamine, can limit these oxidative reactions
      and it can scavenge peroxynitrite independent of iron chelation. Two previous
      studies have examined the therapeutic value of desferrioxamine in EAE. One study
      observed an effect when disease was induced by spinal cord homogenates (J. Exp.
      Med. 160, p. 1532, 1984), but a second study found no therapeutic value of
      desferrioxamine for myelin basic protein (MBP)-induced EAE (J. Neuroimmunol. 17,
      p. 127, 1988). In the second study, the drug was only administered during the
      preclinical stages of disease. Since desferrioxamine scavenges free radicals and
      prevents their formation, we hypothesized that the drug should be given during
      the active stage of disease to have therapeutic value. We first demonstrated that
      the drug enters the CNS around inflammatory cells in EAE animals. In animals
      treated during the active stage of MBP-induced EAE, the clinical signs were
      significantly reduced compared to vehicle-treated animals. The iron-bound form of
      this drug, ferrioxamine, was without therapeutic value. A derivative of
      desferrioxamine, hydroxylethyl starch (HES)-desferrioxamine, has a greater plasma
      half-life than desferrioxamine and it was also tested. Although there was a
      suggestion of improvement in these animals, the effects were less than that
      observed for desferrioxamine which may be related to the greater molecular size
      of HES-desferrioxamine. In summary, these data suggest that chelation of iron is
      an effective therapeutic target for EAE.

PMID- 9628463
TI  - Multiple sclerosis: the frequency of allelic forms of tumor necrosis factor and
      lymphotoxin-alpha.
AB  - The cytokines LTa and TNF have been implicated as major mediators of tissue
      injury in multiple sclerosis (MS). In this study we have assessed the frequency
      of specific polymorphisms for these genes in MS (n = 53) and controls (n = 81)
      using a highly sensitive, two stage nested polymerase chain reaction (PCR), with
      the second stage using mutation-specific primers. Genomic DNA was extracted from
      blood cells and the results confirmed by direct dideoxy chain termination
      sequencing. The frequency of the -308 G to A mutation in the TNF promoter region
      in normal controls was 15% and in MS was 24%. For LTa gene the exon 3
      polymorphism allele A was detected in 36% of controls and 34% of the MS patients.
      In MS, the combined genotype TNF G + A and LTa C + C was present 6 times more
      frequently (12%) than in controls (2%), and patients with this genotype showed
      the highest EDSS scores. We found the TNF and LTa polymorphisms to occur
      independently from the HLA class II DR2 allele distribution in MS. Whilst the G -
      A polymorphism in TNF gene promoter has been studied previously in MS, with
      conflicting results, this is the first study that has addressed the exon 3
      polymorphism in LTa in MS. The results indicate that this polymorphism is not
      linked with the higher genetic predisposition for MS, but that combined TNF G + A
      and LTa C + C genotype might contribute to development of the disease.

PMID- 9628464
TI  - Calcitonin gene-related peptide potentiates LPS-induced IL-6 release from mouse
      peritoneal macrophages.
AB  - The secretion of IL-6 after stimulation of macrophages has been found to play a
      central role in the regulation of defense mechanism, haematopoiesis, and acute
      phase reaction. It was reported that cAMP is involved in the regulation of IL-6
      production. Since calcitonin gene-related peptide (CGRP) is known to increase
      cAMP accumulation in mouse macrophages, we examined whether CGRP would induce IL
      6 release in macrophages. Macrophages were obtained from the peritoneal exudate
      of male Balb/c mouse. The cells were plated on culture dishes at a density of 2.5
      x 10(5) cells per well and allowed to adhere for 2 h. After incubation for 48 h
      with two changes of PRMI-1640, the macrophages were cultured with CGRP and LPS 1
      microg/ml for 12 h. The IL-6 level in medium was measured by ELISA kits. The
      results showed that CGRP had no direct effects on IL-6 production, but it
      potentiated LPS-induced IL-6 production in a concentration-dependent manner. When
      CGRP was at a concentration of 10(-10) M, the LPS-induced IL-6 production was
      increased from 5.16 +/- 0.48 to 8.88 +/- 0.48 ng/ml. The effect of CGRP 10(-10) M
      was reversed by hCGRP(8-37) 10(-8) M, an antagonist of CGRP1 receptor. The LPS
      induced IL-6 production from macrophages was also potentiated by forskolin 5
      microM, an activator of adenylate cyclase. Furthermore, pretreatment with H-89 1
      microM or Rp-cAMPS 100 microM, the inhibitors of cAMP-dependent protein kinase,
      inhibited the effect of CGRP by 31% and 98%, respectively. These results
      demonstrate that the LPS-induced IL-6 release is potentiated by CGRP via the
      activation of cAMP pathway in mouse resident peritoneal macrophages.

PMID- 9628465
TI  - Time-course of interleukin-2 receptor expression in interferon beta-treated
      multiple sclerosis patients.
AB  - The time-course of CD25 (the 55-kD/alpha subunit of the interleukin-2 (IL-2)
      receptor) expression on CD4+ T lymphocytes, and serum levels of soluble IL-2
      receptors (sIL-2R) and IL-2 were evaluated in relapsing-remitting multiple
      sclerosis (RRMS) patients treated with interferon beta-1b (IFNbeta1b). Peripheral
      blood samples were collected before therapy (T0), and 1 (T1), 2 (T2), 3 (T3), 6
      (T4), and 12 (T5) months after therapy initiation. While at T1 and T2, half the
      patients showed an increased number of circulating CD4+ CD25+ lymphocytes and an
      up-regulation of CD25 expression, at T3 this T-cell subset was significantly
      reduced in all the patients. From T4 to T5, however, the progressive return to
      pretreatment values was observed. Serum sIL-2R levels were not significantly
      affected by IFNbeta1b at any time point. IL-2 was detected in only a few patients
      at T0, and never at T1 to T5. The transient up-regulation of CD25+ expression
      that occurred in about 50% of the patients may explain the unchanged relapse rate
      observed during the first 2 to 3 months after starting IFNbeta1b therapy. Our
      study demonstrates that IFNbeta1b down-regulates CD25 expression in vivo. This
      effect, however, was observed only after 3 months of therapy, and was followed by
      the return to pretreatment values after 6 to 12 months. Taken all together, our
      findings suggest that IFNbeta1b only transiently affects CD25 expression in vivo,
      and that this effect cannot account for the reported long-lasting beneficial
      action of IFNbeta1b on RRMS.

PMID- 9628466
TI  - Antibodies to neuroblastoma cell line proteins in patients with schizophrenia.
AB  - The presence of antibodies against neural antigens was investigated in the serum
      of patients with schizophrenia, major depression and normal controls. Different
      immunological abnormalities, humoral and cellular, were reported in schizophrenia
      and major depression. The pathogenesis of schizophrenia is multifactorial. An
      autoimmune mechanism was suggested as a possible factor. We tested the serum of
      26 patients with schizophrenia, eight patients with major depression and 22
      normal controls. The serum samples were tested for antibody binding to protein
      extracts of IMR-32 neuroblastma cell line using Western blot analysis.
      Immunoglobulins of eight patients with schizophrenia (30.71%) reacted with a
      protein of 80-85 kDa. Serum samples from subjects of other groups did not react
      with this protein. Sera of all patients with major depression but one, and all
      normal controls reacted with HSP 60 kDa to different extent. This is an apparent
      discrepancy with the findings of Kilidireas et al. [Kilidireas, K., Latov, N.,
      Strauss, D.H., Gorig, A.D., Hashim, G.A., Gorman, J.M., Sadig, S.A., 1992.
      Antibodies to the human 60 kDa heat shock protein in patients with schizophrenia.
      Lancet 340, 569-572.] who demonstrated the presence of antibodies against HSP 60
      kDa in 44% of patients with schizophrenia tested and 8% of normal subjects. HSP
      60 kDa is an antigen of many pathogens and antibodies against it might be a
      result of an infection and cannot be a good indicator for an autoimmune process.
      The presence of antibodies against a protein of 80-85 kDa should be investigated
      as a possible specific indicator.

PMID- 9628467
TI  - The expression of cytokine mRNA in the cauda equina of Lewis rats with
      experimental allergic neuritis.
AB  - Autoreactive CD4+ T cells can transfer experimental allergic neuritis (EAN) to
      naive recipients. In order to further analyze the role of these T cells and their
      corresponding cytokines in EAN, we studied the expression of mRNA for IFN-gamma,
      IL-4, and IL-10 in the cauda equina of rats with EAN using a quantitative
      competitive reverse transcriptase PCR method. Nerves were studied on days 0 (pre
      immunization), 10 (disease onset), 13 (clinical progression), 16 (disease peak),
      as well as 20, 24, and 34 post immunization (recovery). IFN-gamma messages
      increased at disease onset and peaked at day 13 p.i. IL-10 message remained at a
      very low level at disease onset and surged at day 16. Both messages were low in
      recovery stage. IL-4 message was undetectable at any time point. These data
      suggest a pro-inflammatory role of IFN-gamma and anti-inflammatory role of IL-10
      in EAN lesions. It is also possible that a clonal switch from Th1 to Th2 occurs
      in EAN lesions during the disease course.

PMID- 9628468
TI  - Suppression of acute and protracted-relapsing experimental allergic
      encephalomyelitis by nasal administration of low-dose IL-10 in rats.
AB  - In this study we report for the first time that nasal administration of the Th2
      cell-related cytokine interleukin-10 (IL-10), at concentrations of 1.5 microg/rat
      and 15 microg/rat, suppressed clinical signs of acute experimental allergic
      encephalomyelitis (EAE) in Lewis rats and prevented the development and relapse
      of protracted-relapsing EAE (PR-EAE) in DA rats. In contrast, subcutaneous
      injection of IL-10 (15 microg/rat) did not inhibit acute EAE. The IL-10-mediated
      suppression of EAE was associated with decreased myelin antigen-specific T-cell
      proliferative responses and IFN-gamma secretion in both acute and PR-EAE. In
      sections of spinal cords derived from rats nasally pretreated with IL-10, there
      were no infiltrating CD4+ T cells or macrophages, which are considered as major
      encephalitogenic or inflammatory cells. Most interestingly, nasally administered
      IL-10 also inhibited MHC class II expression in microglia, indicating that IL-10
      administration by the nasal route prevents the activation of microglia.
      Administration of cytokines via the nasal route offers an exciting alternative in
      the prevention and treatment of autoimmune diseases.

PMID- 9628470
TI  - Structure coordinate straw poll.

PMID- 9628469
TI  - Expression of monocyte chemoattractant protein-1 and other beta-chemokines by
      resident glia and inflammatory cells in multiple sclerosis lesions.
AB  - Beta-chemokines induce the directional migration of monocytes and T lymphocytes
      and are thus associated with chronic inflammation. Using immunocytochemistry and
      in situ hybridisation (ISH) techniques, we have examined the expression of the
      beta-chemokines monocyte chemoattractant protein-1 (MCP-1), macrophage
      inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES (regulated upon
      activation, normal T cell expressed and secreted) in post-mortem human brain from
      multiple sclerosis (MS) cases, at different stages of lesion development. In
      actively demyelinating MS plaques RANTES expression was restricted to the blood
      vessel endothelium, perivascular cells and surrounding astrocytes, suggesting a
      role in the recruitment of inflammatory cells from the circulation. MCP-1 was
      expressed by astrocytes and macrophages within acute MS lesions, but was
      restricted to reactive astrocytes in the parenchyma surrounding the lesion. MIP
      1alpha was expressed by astrocytes and macrophages within the plaque, while MIP
      1beta was expressed by macrophages and microglia within the lesion, and by
      microglia in surrounding white matter. Glial cells may be stimulated to produce
      chemokines and continue the local inflammatory response by forming chemotactic
      gradients to attract T cells and mononuclear phagocytes from the circulation and
      surrounding tissue.

PMID- 9628471
TI  - Ion tamers.

PMID- 9628472
TI  - Imperfect interfaces.

PMID- 9628473
TI  - Sensing photons.

PMID- 9628474
TI  - K+ channel gating mechanism proposed using EPR.

PMID- 9628475
TI  - Picture story. Channels, channels everywhere.

PMID- 9628476
TI  - Premonitions of ion channel gating.

PMID- 9628477
TI  - Structural basis for the interaction of Ras with RalGDS.
AB  - The Ras protein signals to a number of distinct pathways by interacting with
      diverse downstream effectors. Among the effectors of Ras are the Raf kinase and
      RalGDS, a guanine nucleotide dissociation stimulator specific for Ral. Despite
      the absence of significant sequence similarities, both effectors bind directly to
      Ras, but with different specificities. We report here the 2.1 A crystal structure
      of the complex between Ras and the Ras-interacting domain (RID) of RalGDS. This
      structure reveals that the beta-sheet of the RID joins the switch I region of Ras
      to form an extended beta-sheet with a topology similar to that found in the Rap
      Raf complex. However, the side chain interactions at the joining junctions of the
      two interacting systems and the relative orientation of the two binding domains
      are distinctly different. Furthermore, in the case of the Ras-RID complex a
      second RID molecule also interacts with a different part of the Ras molecule, the
      switch II region. These findings account for the cross-talk between the Ras and
      Ral pathways and the specificity with which Ras distinguishes the two effectors.

PMID- 9628478
TI  - Solution structure of the thermostable sweet-tasting protein brazzein.
AB  - The fruit of Pentadiplandra brazzeana Baillon contains a small, sweet-tasting
      protein named brazzein. The structure of brazzein in solution was determined by
      proton nuclear magnetic resonance spectroscopy at pH 5.2 and 22 degrees C. The
      brazzein fold, which contains one alpha-helix and three strands of antiparallel
      beta-sheet, does not resemble that of either of the other two sweet-tasting
      proteins with known structures, monellin and thaumatin. Instead, the structure of
      brazzein resembles those of plant gamma-thionins and defensins and arthropod
      toxins. Sequence comparisons predict that members of a newly-identified family of
      serine proteinase inhibitors share the brazzein fold.

PMID- 9628479
TI  - Structure of the dimer initiation complex of HIV-1 genomic RNA.
AB  - Retroviral genomes must dimerize to be fully infectious. Dimerization is directed
      by a unique RNA hairpin structure with a palindrome in its loop: hairpins of two
      strands first associate transiently through their loops, and then refold to a
      more stable, linear duplex. The structure of the initial, kissing-loop dimer from
      HIV-1, solved using 2D NMR, is bent and metastable, its interface being formed
      not only by standard basepairing between palindromes, but also by a distinctive
      pattern of interstrand stacking among bases at the stem-loop junctions. This
      creates mechanical distortions that partially melt both stems, which may
      facilitate spontaneous refolding of this RNA complex into linear form.

PMID- 9628480
TI  - The structure of PurR mutant L54M shows an alternative route to DNA kinking.
AB  - The crystal structure of the purine repressor mutant L54M bound to hypoxanthine
      and to the purF operator provides a stereochemical understanding of the high DNA
      affinity of this hinge helix mutant. Comparison of the PurR L54M-DNA complex to
      that of the wild type PurR-DNA complex reveals that these purine repressors bind
      and kink DNA similarly despite significant differences in their minor groove
      contacts and routes to interdigitation of the central C.G:G.C base pair step.
      Modeling studies, supported by genetic and biochemical data, show that the
      stereochemistry of the backbone atoms of the abutting hinge helices combined with
      the rigidity of the kinked base pair step constrain the interdigitating residue
      to leucine or methionine for the LacI/GalR family of transcription regulators.

PMID- 9628481
TI  - Crystal structure of E.coli RuvA with bound DNA Holliday junction at 6 A
      resolution.
AB  - Here we present the crystal structure of the Escherichia coli protein RuvA bound
      to a key DNA intermediate in recombination, the Holliday junction. The structure,
      solved by isomorphous replacement and density modification at 6 A resolution,
      reveals the molecular architecture at the heart of the branch migration and
      resolution reactions required to process Holliday intermediates into recombinant
      DNA molecules. It also reveals directly for the first time the structure of the
      Holliday junction. A single RuvA tetramer is bound to one face of a junction
      whose four DNA duplex arms are arranged in an open and essentially four-fold
      symmetric conformation. Protein-DNA contacts are mediated by two copies of a
      helix-hairpin-helix motif per RuvA subunit that contact the phosphate backbone in
      a very similar manner. The open structure of the junction stabilized by RuvA
      binding exposes a DNA surface that could be bound by the RuvC endonuclease to
      promote resolution.

PMID- 9628482
TI  - Chemotaxis receptor recognition by protein methyltransferase CheR.
AB  - Signal transduction processes commonly involve reversible covalent modifications
      of receptors. Bacterial chemotaxis receptors are reversibly methylated at
      specific glutamate residues within coiled-coil regions of their cytoplasmic
      domains. Methylation is catalyzed by an S-adenosylmethionine-dependent protein
      methyltransferase, CheR, that binds to a specific sequence at the C-termini of
      some chemotaxis receptors. From this tethering point, CheR methylates neighboring
      receptor molecules. We report the crystal structure, determined to 2.2 A
      resolution, of a complex of the Salmonella typhimurium methyltransferase CheR
      bound to the methylation reaction product, S-adenosylhomocysteine (AdoHcy), and
      the C-terminal pentapeptide of the aspartate receptor, Tar. The structure
      indicates the basis for the specificity of interaction between the chemoreceptors
      and CheR and identifies a specific receptor binding motif incorporated in the
      CheR methyltransferase domain.

PMID- 9628483
TI  - Tubulin and FtsZ form a distinct family of GTPases.
AB  - Tubulin and FtsZ share a common fold of two domains connected by a central helix.
      Structure-based sequence alignment shows that common residues localize in the
      nucleotide-binding site and a region that interacts with the nucleotide of the
      next tubulin subunit in the protofilament, suggesting that tubulin and FtsZ use
      similar contacts to form filaments. Surfaces that would make lateral interactions
      between protofilaments or interact with motor proteins are, however, different.
      The highly conserved nucleotide-binding sites of tubulin and FtsZ clearly differ
      from those of EF-Tu and other GTPases, while resembling the nucleotide site of
      glyceraldehyde-3-phosphate dehydrogenase. Thus, tubulin and FtsZ form a distinct
      family of GTP-hydrolyzing proteins.

PMID- 9628484
TI  - Three-dimensional architecture and gating mechanism of a K+ channel studied by
      EPR spectroscopy.
AB  - The transmembrane organization of a potassium channel from Streptomyces lividans
      has been studied using site-directed spin labeling techniques and electron
      paramagnetic resonance spectroscopy. In the tetrameric channel complex, two alpha
      helices were identified per monomer and assigned to the amino acid sequence.
      Probe mobility and accessibility data clearly establish that the first helix
      (TM1) is located in the perimeter of the channel, showing extensive protein-lipid
      contacts, while the second helix (TM2) is closer to the four-fold symmetric axis
      of the channel, lining the intracellular vestibule. A large conformational change
      in the C-terminal end of TM2 was measured when comparing conditions that favor
      either the open or closed states. The present data suggest that the diameter of
      the internal vestibule increases with channel opening.

PMID- 9628485
TI  - Design, structure and stability of a hyperthermophilic protein variant.
AB  - Here we report the use of an objective computer algorithm in the design of a
      hyperstable variant of the Streptococcal protein Gbeta1 domain (Gbeta1). The
      designed seven-fold mutant, Gbeta1-c3b4, has a melting temperature in excess of
      100 degrees C and an enhancement in thermodynamic stability of 4.3 kcal mol(-1)
      at 50 degrees C over the wild-type protein. Gbeta1-c3b4 maintains the Gbeta1
      fold, as determined by nuclear magnetic resonance spectroscopy, and also retains
      a significant level of binding to human IgG in qualitative comparisons with wild
      type. The basis of the stability enhancement appears to have multiple components
      including optimized core packing, increased burial of hydrophobic surface area,
      more favorable helix dipole interactions, and improvement of secondary structure
      propensity. The design algorithm is able to model such complex contributions
      simultaneously using empirical physical/chemical potential functions and a
      combinatorial optimization algorithm based on the dead-end elimination theorem.
      Because the design methodology is based on general principles, there is the
      potential of applying the methodology to the stabilization of other unrelated
      protein folds.

PMID- 9628486
TI  - Crystal structure of calsequestrin from rabbit skeletal muscle sarcoplasmic
      reticulum.
AB  - Calsequestrin, the major Ca2+ storage protein of muscle, coordinately binds and
      releases 40-50 Ca2+ ions per molecule for each contraction-relaxation cycle by an
      uncertain mechanism. We have determined the structure of rabbit skeletal muscle
      calsequestrin. Three very negative thioredoxin-like domains surround a
      hydrophilic center. Each monomer makes two extensive dimerization contacts, both
      of which involve the approach of many negative groups. This structure suggests a
      mechanism by which calsequestrin may achieve high capacity Ca2+ binding. The
      suggested mechanism involves Ca2+-induced collapse of the three domains and
      polymerization of calsequestrin monomers arising from three factors: N-terminal
      arm exchange, helix-helix contacts and Ca2+ cross bridges. This proposed
      structure-based mechanism accounts for the observed coupling of high capacity
      Ca2+ binding with protein precipitation.

PMID- 9628488
TI  - Dr. Miller goes to Washington: you should, too.
AB  - Otolaryngologists, like most physicians, tend to avoid local, state, and national
      politics for a variety of reasons. Although physicians and their patients are
      frequently affected by policies made in these political arenas, physicians tend
      to avoid active participation because of inexperience, lack of time, lack of
      knowledge about ways to influence policy development, and a general distaste for
      the political process. Otolaryngologists need to participate in the process to
      ensure that their particular perspectives and concerns are heard. However,
      otolaryngologists also need to look beyond their personal or specialty interests
      to influence the broader health care debate. Before we are specialists, we are
      first physicians who have a fiduciary responsibility to mankind (our patients) to
      improve the health care system for all Americans. We have a moral and ethical
      obligation to address, influence, and support health care beyond the specialty
      level. Health policy developed in an absence of physician input is missing the
      insight of expertise and experience.

PMID- 9628487
TI  - A new DNA-binding motif in the Skn-1 binding domain-DNA complex.
AB  - The DNA-binding domain of Skn-1, a developmental transcription factor that
      specifies mesoderm in C. elegans, is shown by X-ray crystallography to have a
      novel fold in which a compact, monomeric, four-helix unit organizes two DNA
      contact elements. At the C-terminus, a helix extends from the domain to occupy
      the major groove of DNA in a manner similar to bZip proteins. Skn-1, however,
      lacks the leucine zipper found in all bZips. Additional contacts with the DNA are
      made by a short basic segment at the N-terminus of the domain, reminiscent of the
      'homeodomain arm'.

PMID- 9628489
TI  - Conservation of resources: indications for intensive care monitoring after upper
      airway surgery on patients with obstructive sleep apnea.
AB  - Although significant complications can result after upper airway surgery for
      obstructive sleep apnea (OSA), there is a lack of consensus regarding the most
      appropriate level of monitoring in the perioperative period. A retrospective
      analysis was performed on the operative records of 109 adult patients who
      underwent 125 surgical procedures from January 1, 1991, to May 31, 1996, with
      particular emphasis on complications that would have mandated intensive care
      monitoring and management. Airway complications occurred in one patient (0.8%),
      who became obstructed immediately after surgery; he responded to naloxone and
      suctioning. Five other patients (4%) suffered oxygen desaturation to levels below
      90% (none fell below 80%, and in only one case was it below the lowest
      preoperative oxygen saturation level). Cardiac complications, primarily
      significant hypertension, were the most common adverse events. Four (3.2%)
      bleeding complications were encountered; all occurred after discharge from the
      hospital. Routine postoperative intensive care monitoring for all adult patients
      undergoing upper airway surgery for OSA is unnecessary. Although high-risk
      patients cannot always be identified preoperatively, significant complications
      generally emerge within 2 hours after surgery. Therefore a decision regarding the
      level of postoperative monitoring needed may be made with confidence during the
      period of time that the patient is in the recovery room.

PMID- 9628490
TI  - Cephalometric parameters after multilevel pharyngeal surgery for patients with
      obstructive sleep apnea.
AB  - Cephalometric studies have shown narrowing in the upper airway at multiple levels
      in patients with obstructive sleep apnea. Uvulopalatopharyngoplasty (UPPP),
      mandibular osteotomy with genioglossus advancement, and hyoid myotomy with
      advancement address narrowing in the retropalatal and retrolingual regions. In an
      effort to relate postoperative clinical changes to anatomic changes,
      cephalometric studies were performed on 44 patients who underwent multilevel
      pharyngeal surgery (UPPP, genioglossus advancement, hyoid myotomy with
      advancement). Both pre- and postoperative radiographs were available for 23 of
      these patients. The posterior airway space (P = .09), minimal posterior airway
      space (P = .04), posterior uvular space (P = .06), mandibular plane-to-hyoid
      distance (MP-H) (P = .06) and central incisor-to-tongue base distance (P = .02)
      all improved after surgery. None of the measurements of the posterior airway were
      significantly different between responders and nonresponders. The degree of
      collapse of the palate on modified Muller maneuver was highly correlated with the
      severity of sleep apnea as measured by the respiratory disturbance index; the
      collapse of the lateral pharyngeal walls was moderately correlated; and collapse
      of the base of tongue was not correlated. Cephalometric radiographs may reflect
      the anatomic changes that result from upper airway surgery for sleep apnea, but
      these changes are not useful for assessing surgical efficacy. The modified Muller
      maneuver, however, may represent a more predictive evaluation.

PMID- 9628491
TI  - Meta-analysis of outcomes of pediatric functional endoscopic sinus surgery.
AB  - OBJECTIVE: To create a consensus of outcomes of pediatric functional endoscopic
      sinus surgery (FESS) and assess its effectiveness and safety. STUDY DESIGN: A
      meta-analysis of the literature on outcomes of pediatric FESS. METHODS: A meta
      analysis of the literature was performed focusing on the number of patients per
      study, length of follow-up, prospective versus retrospective, and the separation
      or exclusion of patients with significant underlying systemic diseases (cystic
      fibrosis and immunodeficiencies). A rating scale based on the above criteria was
      used to select articles for inclusion. RESULTS: Eight published articles (832
      patients) plus unpublished data from the authors' institution (50 patients) were
      included. The "positive" outcome rates for published, unpublished, and combined
      data were 88.4%, 92%, and 88.7%, respectively. No statistically significant
      differences in "positive" outcome existed between all published or unpublished
      series using a chi-squared test (power = .51, P = .38). The average combined
      follow-up was 3.7 years, with a major complication rate of 0.6%. CONCLUSION:
      Pediatric FESS is a safe and effective treatment for chronic sinusitis that is
      refractory to medical therapy.

PMID- 9628492
TI  - Observations on control of N2 and N3 neck disease in squamous cell carcinoma of
      the head and neck by intra-arterial chemoradiation.
AB  - Patients with head and neck squamous cell cancer with N2 and N3 neck disease have
      a poor prognosis and are at risk to fail regionally despite combined surgery and
      radiation. Twenty-two patients with N2 and N3 neck disease (and T3-4 primaries)
      were treated with intra-arterial, high-dose cisplatin (CDDP), 150 mg/m2 per week
      for 4 weeks, and concurrent radiation. All patients were followed for at least 2
      years or until death from any cause. Twenty patients had a complete response at
      the primary site. Two of the 20 with a complete response later had a neck
      recurrence and died. Five patients with palpable nodes after treatment underwent
      fine-needle aspiration (FNA), one of which was positive and two suggestive of
      cancer. Six neck dissections were performed in this group, only two of which had
      positive nodes. This chemoradiation protocol may offer reasonable control of N2
      and N3 neck disease in advanced head and neck squamous cell cancer. Neck
      dissection appeared to be necessary in only those patients with nodes 8 weeks
      after treatment in whom FNA was positive or suggestive of cancer. Because of the
      relatively small size of this series, additional accrual and monitoring of such
      patients is planned.

PMID- 9628493
TI  - Relationship between quality of life and depression in patients with head and
      neck cancer.
AB  - OBJECTIVE: This study describes the relationship between health-related quality
      of life (HRQOL) and depression in patients following major surgery for head and
      neck cancer. DESIGN: Cross-sectional study using medical chart review, patient
      interview, and test administration. METHOD: Fifty patients were evaluated 6
      months to 6 years following surgery using one global HRQOL measure (The
      Functional Assessment of Cancer Therapy-General [FACT-G]); three disease-specific
      measures of HRQOL (the HN module of the FACT [FACT-HNS], The University of
      Washington Quality of Life Scale [UWQOL], and The Performance Status Scale for
      Head and Neck Cancer); and one measure of depression (The Beck Depression
      Inventory [BDI]). RESULTS: The study population showed a high occurrence of
      depressive symptoms (22%). A negative correlation existed between the BDI and
      HRQOL as measured by the FACT-G (r = -0.49, P < .001) and the UWQOL (r = -0.44, P
      = .003). When somatic symptoms of depression were removed, the BDI remained
      correlated with HRQOL and was most highly correlated with the Emotional Well
      Being (EWB) subscale of the FACT-G (r = -0.42, P = .003). There was no
      correlation between clinician judgments of EWB and any patient-rated measures of
      HRQOL or depression. CONCLUSIONS: Results demonstrate an inverse relationship
      between patient-reported HRQOL and depression. The lack of correlation between
      physician and patient ratings of HRQOL and EWB stresses the importance of
      obtaining patient ratings in addition to traditional clinician ratings when
      assessing outcomes. Finally, the multidimensional construction of the FACT with
      its specific subscales may make it a useful clinical tool for assessing patient
      status and augmenting patient interviews.

PMID- 9628494
TI  - Significance of unilateral submandibular gland excision on salivary flow in
      noncancer patients.
AB  - OBJECTIVES/HYPOTHESIS: Normal salivary flow is important for maintaining good
      oral hygiene. Lack of normal flow predisposes to an increased incidence of dental
      caries and symptomatic xerostomia. The submandibular glands are responsible for
      70% of resting salivary flow. Removal of the submandibular gland is most commonly
      performed for sialolithiasis, chronic sialoadenitis, or as part of a neck
      dissection. The effect of unilateral gland resection for benign disease on
      resting salivary flow has not been well examined in the literature. STUDY DESIGN:
      Case controlled study involving patients who had undergone a unilateral
      submandibular gland resection matched with normal control subjects. METHOD:
      Stimulated and unstimulated salivary flow rates in surgical and control subjects
      were measured in a controlled setting. RESULTS: Unstimulated salivary flow rates
      were 0.805 mL/min in the control group and 0.405 mL/min in the surgical group (P
      = .01). Stimulated salivary flow rates were not significantly different between
      the two groups (P > .05). Fifty-seven percent of patients in the surgical group
      and 14% in the control group had xerostomia (P < .05). CONCLUSION: Unilateral
      submandibular gland excision results in a decreased rate of resting salivary flow
      and an increase in subjective xerostomia.

PMID- 9628495
TI  - Pediatric temporal bone fractures.
AB  - OBJECTIVE: To examine the etiology, presentation, and management of temporal bone
      fractures in children. STUDY DESIGN: Case control. METHOD: Retrospective review
      of a level I pediatric trauma center from July 1, 1990 to November 1, 1996
      identified 680 patients. Inclusion criteria of age less than 14 years and only
      blunt temporal bone trauma identified 122 patients, with 97 charts available for
      review. The criteria for temporal bone fracture consisted of both clinical and
      radiologic information. Only patients with temporal bone fractures confirmed by
      computed tomography, a complete otolaryngology examination, and audiometric
      evaluations were included in the study. The data were analyzed with the Kruskal
      Wallis analysis of variance (ANOVA) for examining the three separate age groups
      of fractures. Chi-squared analysis was used to compare these data with previously
      published adult and pediatric temporal bone fracture series and to examine the
      three separate age groups of fractures. RESULTS: The review identified 72
      children with 79 temporal bone fractures: 47 boys and 25 girls. The patients
      ranged from 6 months to 14 years of age, with a bimodal distribution of patients
      with peaks at 3 years and 12 years of age. The most common causes of fractures
      were motor vehicle accidents (47%), falls (40%), biking accidents (8%), and blows
      to the head (7%). Common presenting signs and symptoms included hearing loss
      (82%), hemotympanum (81%), loss of consciousness (63%), intracranial injuries
      (58%), bloody otorrhea (58%), extremity fractures (8%), and facial nerve weakness
      (3%). The most common causes of temporal bone fractures were falls and motor
      vehicle accidents. Forty-two patients were noted to have bloody otorrhea and
      possible cerebrospinal fluid leak. Twenty-four received intravenous antibiotics.
      No patient developed prolonged otorrhea or meningitis during hospitalization and
      the follow-up period. The classification of fracture patterns was longitudinal,
      54%; transverse, 6%; oblique, 10%; squamous, 27%; and other, 3%. Hearing loss was
      found in 59 patients, with conductive hearing loss being the most common finding
      in 56% of the patients, followed by sensorineural hearing loss in 17% and mixed
      hearing loss in 10%. CONCLUSIONS: Pediatric temporal bone fractures are
      associated with falls and motor vehicle accidents. There is a high incidence of
      associated intracranial injuries and hearing loss, but facial nerve injuries are
      uncommon. Timely management minimizes complications.

PMID- 9628496
TI  - Contemporary presentation and management of a spectrum of mastoid abscesses.
AB  - BACKGROUND: The incidence of complications resulting from suppurative otitis
      media has significantly decreased since the introduction of antibiotics. At the
      start of the 20th century 50% of all cases of otitis media developed a coalescent
      mastoiditis. By 1959, the incidence had fallen to 0.4%. Recent studies suggest a
      current incidence of only 0.24%. Additionally, during the time of Friedrich
      Bezold (1824-1908), 20% of patients with mastoiditis developed subperiosteal
      abscess. Interestingly, this has incidence increased; today nearly 50% of
      patients diagnosed with coalescent mastoiditis have subperiosteal abscess.
      OBJECTIVE: To review the contemporary presentation, diagnosis, and management of
      a spectrum of mastoid abscesses. DESIGN: Retrospective case series. SETTING:
      Hospitals associated with the Department of Otolaryngology/Head and Neck Surgery
      at the University of California, San Francisco. PATIENTS: Three patients with
      mastoid abscesses are reported. One patient displayed "classic" Bezold's abscess,
      with pus escaping the mastoid near the incisura digastrica and tracking along the
      digastric and sternocleidomastoid muscles into the neck. The second and third
      patients exhibited temporoparietal swelling secondary to mastoid abscess eroding
      the root of the zygomatic process, a complication noted by Bezold in 1908 as
      occurring "in only very rare cases." RESULTS AND CONCLUSIONS: Since only one
      third of patients show pathologic tympanic membrane changes, and since complaints
      of otalgia, fever, and tenderness are inconstant, subperiosteal mastoid abscess
      is frequently a delayed diagnosis. The clinical presentation, pathogenesis, and
      routes of abscess spread are presented with photographic and radiographic
      illustration. Medical and surgical management is reviewed, and methods for
      accurate diagnosis are emphasized.

PMID- 9628497
TI  - Bone cement reconstruction of the ossicular chain: a preliminary report.
AB  - OBJECTIVE: To determine the feasibility and efficacy of using a bone cement, Oto
      Cem, to reconstruct the ossicular chain. STUDY DESIGN: Prospective clinical trial
      on nine consecutively chosen adult patients with ossicular chain defects.
      PATIENTS AND SETTING: Nine patients with ossicular chain defects involving the
      long process of the incus were treated at the Carolina Ear and Hearing Clinic.
      The ossicular chain was reconstructed using bone cement by itself or in
      conjunction with a stapes prosthesis. MAIN OUTCOME MEASURES: Preoperative
      audiograms were compared with audiograms 3, 6, and 12 months after
      reconstruction. RESULTS: There was a mean pure-tone average (PTA) improvement of
      15 dB in patients undergoing incus to stapes suprastructure reconstruction with
      the bone cement. The incus to mobile footplate reconstruction (using a stapes
      prosthesis attached to the newly reconstructed incus) resulted in a 34-dB PTA
      postoperative improvement. Two of the three patients with incus to oval window
      repairs experienced a 10-dB improvement in PTA. One of the three patients
      experienced a loss in speech discrimination and a 2-dB loss in PTA. CONCLUSIONS:
      Despite the limited number of patients, this preliminary study demonstrates the
      effectiveness of Oto-Cem in reconstructing a foreshortened incus. There was a
      substantial hearing improvement in all but one patient in the incus to stapes or
      the incus to footplate categories.

PMID- 9628498
TI  - Distortion-product otoacoustic emission monitoring of cochlear blood flow.
AB  - Distortion-product otoacoustic emissions (DPOAEs) have been shown to be ideally
      sensitive to interruptions of the cochlear blood flow. However, a 15- to 30
      second latency typically occurs between cessation of circulation and measurable
      DPOAE level changes. DPOAEs can also be characterized by phase measures. The aim
      of the present study was to determine in 10 rabbits the effects on DPOAE phase of
      repetitively compressing the internal auditory artery. In contrast to the delays
      measured by DPOAE level, phase changes were detected 1 to 5 seconds after
      internal auditory artery compression. These data suggest that the essentially
      "real time" monitoring of cochlear function with DPOAE phase can be used to
      ensure hearing preservation during surgery involving the porus acousticus and
      skull base.

PMID- 9628499
TI  - Effect of pulse duration on wound healing using a CO2 laser.
AB  - The authors investigated wound healing of incisions in the buccal mucosa of a
      canine model created using a CO2 laser with a short pulse structure (60 micros,
      100 micros, and 120 micros) rather than a conventional continuous wave structure
      in a shuttered mode. The tissue from 10 animals was evaluated histologically and
      with tensiometry acutely and at postoperative days 3, 7, and 14. A Bonferroni
      Dunn corrected ANOVA analysis at a 95% significance level was used to compare the
      effect of pulse duration on histologic morphology and wound tensile strength. The
      data indicate that shorter laser pulse durations create less lateral thermal
      injury (P < .009) and wounds with greater tensile strength (P < .005), resulting
      in earlier wound healing. The results also show that heat, sufficient to damage
      tissue, was conducted to adjacent tissue during laser pulses of 100 micros and
      longer. These results demonstrate that surgical CO2 lasers with a short pulse
      structure of approximately 60 micros or less could offer more prompt wound
      healing while maintaining the advantages of a 10.6-microm wavelength laser.

PMID- 9628500
TI  - Tracheal transplantation: superior and inferior thyroid artery perfusion
      territory.
AB  - OBJECTIVE: To determine the perfusion territories of the superior and inferior
      thyroid arteries in humans. Tracheal transplantation is a potential option for
      management of long-segment tracheal stenosis. However, the maximum length of
      vascularized trachea that can be reliably transplanted has not been established.
      STUDY DESIGN: The tracheal vascular territory of individual superior and inferior
      thyroid arteries was determined separately in 10 humans postmortem. METHODS:
      India ink was infused unilaterally under controlled pressure into the superior (n
      = 5) and inferior (n = 5) thyroid arteries of cadaveric tracheas. Tracheas were
      sectioned longitudinally and the caudalmost extent of mucosal dye staining was
      determined via microscopic assessment. RESULTS: The tracheal perfusion territory
      of the superior thyroid artery was two to five rings (1.7 +/- 0.5 cm) and the
      inferior thyroid artery, nine to 13 rings (6.5 +/- 1.1 cm). In both cases, the
      tracheal mucosa on the contralateral side was stained to the same caudal level.
      CONCLUSIONS: The inferior thyroid artery was shown to perfuse the trachea
      maximally to the 13th ring (8.1 cm). As such, the unilateral inferior thyroid
      artery would serve as a suitable vascular component for long-segment tracheal
      transplantation in humans.

PMID- 9628501
TI  - Subglottic injury, gastric juice, corticosteroids, and peptide growth factors in
      a porcine model.
AB  - OBJECTIVES: To study the effects of mucosal injury, gastric juice, and
      corticosteroids and to determine the presence of peptide growth factors in the
      subglottic mucosa in a porcine model. STUDY DESIGN: Prospective cohort animal
      study. METHODS: In this model of subglottic injury, five groups (n = 5 each) of
      piglets were used. Injury was induced by electrocautery (acute), electrocautery
      plus repeated saline application (chronic), electrocautery plus repeated gastric
      juice application (chronic plus gastric juice), or repeated gastric juice
      application (gastric). Control piglets had normal saline applied repeatedly.
      RESULTS: Histopathologic findings for the gastric juice group included basal cell
      hyperplasia (80%), squamous metaplasia (80%), and mucosal ulceration (40%).
      Control piglets showed squamous metaplasia (80%) but no basilar hyperplasia or
      ulceration. Immunohistochemistry detected peptide growth factors and epidermal
      growth factor receptor (EGFR) in all groups. Decreased staining was most frequent
      in the acute injury group. Quantitative reverse transcriptase polymerase chain
      reaction (RT-PCR) documented lower expression of EGFR in the gastric juice group
      (P = .01). CONCLUSIONS: These findings suggest that peptide growth factors and
      EGFR are part of normal subglottic mucosal turnover. Noxious stimuli decrease
      production of these factors. Gastric juice had adverse effects documented by
      histopathology and molecular techniques.

PMID- 9628502
TI  - Correlation of laryngeal chemoreflex severity with laryngeal muscle response.
AB  - OBJECTIVES: To examine the relationship between the severity of the laryngeal
      chemoreflex (LCR) and the pattern of laryngeal muscle activity during an LCR
      induced apnea. METHODS: The laryngeal mucosa of 20 piglets aged 17 to 20 days was
      stimulated under both hypoxic and normoxic conditions. Respiration, blood
      pressure, and activity of the thyroarytenoid (TA) and posterior cricoarytenoid
      (PCA) muscles were monitored during the LCR-induced apnea. RESULTS: Hypoxemia
      resulted in a shorter average apnea duration but a greater degree of hypotension.
      All piglets recovered spontaneously following normoxic LCR stimulation. Hypoxic
      stimulation resulted in two divergent apneic responses: transient with a
      spontaneous recovery (17 piglets) or profound requiring resuscitation (three
      piglets). An increase in TA muscle activity and a decrease in PCA muscle activity
      was the most common response to LCR stimulation. The response of the TA and PCA
      muscles was maintained in piglets destined for spontaneous recovery. Decreasing
      TA activity and increasing PCA activity correlated with the development of a
      profound response. CONCLUSIONS: The piglet demonstrates two distinct responses to
      hypoxic laryngeal chemostimulation that correlate with the activity of the
      intrinsic laryngeal muscles. Failure to maintain the activity of the TA and PCA
      muscles during a profound response is associated with the development of severe
      cardiovascular instability. This study suggests that the critical event involving
      the LCR is the development of complications secondary to hypoxia.

PMID- 9628503
TI  - Endoscopic optic nerve decompression: the Graz experience.
AB  - Recommendations for management of traumatic injuries to the optic nerve in the
      literature include expectant management, medical therapy, surgical treatment, and
      medical therapy combined with surgical decompression. Traditional surgical
      approaches to optic nerve decompression (OND) are a neurosurgical or craniotomy
      approach, extranasal transethmoidal approach, transorbital approach, transantral
      approach, and intranasal microscopic approach. Recent advances in instrumentation
      and surgical techniques have made an endoscopic approach to OND possible. Since
      1991 endonasal endoscopic decompression of the optic nerve has been the surgical
      approach of choice in patients requiring OND in the authors' hospital. The
      endoscopic method offers many advantages over the traditional approaches.
      Decreased morbidity, preservation of olfaction, rapid recovery time, more
      acceptable cosmetic results with no external scars, no risk of injury to the
      developing teeth in children, and less operative stress in a patient who may have
      multisystem trauma are only some of the benefits associated with the endoscopic
      OND. The authors' technique of endonasal endoscopic approach to OND, medical
      management, and indications for surgery and the results in 22 patients undergoing
      this procedure are discussed.

PMID- 9628504
TI  - Sinus surgery: does mitomycin C reduce stenosis?
AB  - This experimental study investigates the effect of mitomycin C (MMC) on sinus
      mucosal healing. MMC has an antiproliferative action on fibroblasts. It is used
      in glaucoma surgery to prevent restenosis of fistulas. Antrostomies were drilled
      in rabbit maxillary sinuses. One side was used as a control and the other treated
      with MMC at a concentration of 0.04, 0.4, or 1 mg/mL. Two animals from each group
      were sacrificed at 1, 2, 4, and 12 weeks. The antrostomies in the control and
      0.04-mg/mL groups had closed by 1 week; in the 0.4-mg/mL group by 4 weeks, and in
      the 1.0-mg/mL group by 12 weeks. Ciliary function was initially impaired but
      normalized within 1 week. Both light and scanning electron microscopy showed no
      permanent damage to the cilia. These results suggest that MMC can be used to
      delay closure of antrostomies in sinus surgery.

PMID- 9628505
TI  - Supraselective embolization in intractable epistaxis: review of 45 cases.
AB  - Epistaxis is a common and in most cases benign event. Severe or recurrent
      epistaxis, however, can present therapeutic problems. Forty-five cases of
      supraselective embolization in intractable epistaxis are reported. The authors'
      success rate of 97%, similar to the success rates reported in the literature,
      confirms the effectiveness of this technique. Complications occurred in only 8%
      of the cases. One serious complication was neurologic. Percutaneous embolization
      is an effective option for managing intractable posterior nasal bleeding but is
      not recommended as an early form of treatment.

PMID- 9628506
TI  - Objective measures of laryngeal function after reinnervation of the anterior and
      posterior recurrent laryngeal nerve branches.
AB  - Previous research indicates that separate reinnervation of the anterior and
      posterior branches of the recurrent laryngeal nerve (RLN) can provide purposeful
      motion of the larynx, even after transplantation. This canine study was
      undertaken to better determine the results of RLN reinnervation after nerve
      transection distal to its bifurcation. This approximates ideal conditions for
      transplantation, because potential rejection and nerve branch mismatch are
      eliminated. Eight months after nerve repair, video, electromyographic,
      mechanical, and histologic data were collected on four canines. Results show
      return of appropriate motion without synkinesis, including purposeful abduction
      on endotracheal tube occlusion. Abductory function was weaker on the reinnervated
      side, but adduction was equal or stronger on the reinnervated vocal cord. These
      results indicate that this method of RLN reinnervation produces consistent,
      strong physiologic motion in the denervated larynx.

PMID- 9628507
TI  - Posterior laryngeal clefts: preliminary report of a new surgical procedure using
      tibial periosteum as an interposition graft.
AB  - OBJECTIVE: To present the preliminary results of a new surgical procedure for
      posterior laryngeal cleft repair. DESIGN: Retrospective study in an academic
      tertiary care center. METHOD: The study included three male patients (age at
      surgery, 2, 13, and 14 mo). One presented with severe aspiration and cyanotic
      attacks, the two others with aspiration and recurrent chest infections. The types
      of laryngeal clefts included complete cleft of the cricoid with varying degrees
      of tracheal involvement but not further than the first six tracheal rings.
      Associated malformations included one VATER syndrome, one esophageal atresia, and
      one tracheoesophageal fistula. Surgery was performed under general anesthesia
      with nasotracheal intubation. A vertical anterior laryngofissure was performed.
      The mucosal margins of the clefts were incised and then repaired in two layers
      with polyglactin sutures. The original feature of this procedure was the
      interposition of a small piece of tibial periosteum between the two layers. This
      fascia graft is known to be strong and resistant in cleft palate surgery. MAIN
      OUTCOME MEASURE: Clinical and endoscopic follow-up was used for evaluation of
      results. RESULTS: The three patients had successful laryngeal repair at a mean
      follow-up of 6 months (range, 4-14 mo). CONCLUSION: The anterior laryngofissure
      provides a good surgical access to the cleft. The interposition of tibial
      periosteum allows durability of the cleft repair. A longer follow-up is needed to
      confirm these preliminary results. A computed tomography scan study and a study
      on the rabbit are planned in order to evaluate the outcome of these periosteal
      grafts.

PMID- 9628508
TI  - Postinflammatory acquired atresia of the external auditory canal: treatment and
      results of surgery over 27 years.
AB  - Postinflammatory, acquired atresia of the external auditory meatus is a
      relatively rare consequence of chronic otitis media or recurrent external otitis
      with an annual incidence of 0.6 cases per 100,000 inhabitants. Primary and late
      results after operative treatment of this condition in 53 ears over 27 years are
      presented. Perioperative findings are described, and an outline of applied
      surgical technique is given. Six patients had bilateral involvement. The male-to
      female ratio was 1:2, median age at surgery was 46 years, and the median follow
      up period was 5 years (range, 4 mo to 13 y). In 11% of the cases, recurrent
      atresia developed. Early operation is recommended, because cholesteatoma behind
      the atresia was found in 9%. Hearing improvement has been considerable after
      removal of the atresia with primary closure of airbone gap within 20 dB in 90% of
      the cases.

PMID- 9628509
TI  - Surgical variables affecting speech in treated patients with oral and
      oropharyngeal cancer.
AB  - Postoperative speech function may be influenced by a number of treatment
      variables. The objective of this study was to examine the relationships among
      various treatment factors to determine the impact of these measures on speech
      function. Speech function was tested prospectively in 142 patients with
      surgically treated oral and oropharyngeal cancer 3 months after treatment. Each
      patient's speech was recorded during a 6- to 7-minute conversation and while
      performing a standard articulation test, producing speech outcome measures of
      percent correct consonant phonemes and percent conversational understandability.
      Correlational analyses were used to determine the relationships among the speech
      outcome measures and 14 treatment parameters. Speech function was mildly to
      moderately negatively correlated with most surgical resection variables,
      indicating that larger amounts of tissue resected were associated with worse
      speech function. Overall measures of conversational understandability and percent
      correct consonant phonemes were related to extent of oral tongue resection, floor
      of mouth resection, soft palate resection, and total volume of tissue resected.
      These relationships varied depending on the method of surgical closure. Method of
      surgical reconstruction had a profound impact on postoperative speech function 3
      months after treatment and was an important factor in determining how oral tongue
      resection influenced articulation and intelligibility. The combination of closure
      type, percent oral tongue resected, and percent soft palate resected had the
      strongest relationship with overall speech function for patients with surgically
      treated oral and oropharyngeal cancer 3 months after treatment.

PMID- 9628510
TI  - Oral leukoplakias show numerical chromosomal aberrations detected by fluorescence
      in situ hybridization.
AB  - To examine at which stage in the multistep process of head and neck tumorigenesis
      numerical chromosomal alterations can be detected by fluorescence in situ
      hybridization (FISH), biopsies and cell smear preparations of clinically healthy
      oral tissue, premalignant lesions (leukoplakias), and tumors were analyzed by
      FISH using chromosome-specific centromeric probes. Aberrations found in tumor
      biopsies and in tumor cell smears consisted of trisomy of chromosomes 1, 7, 10,
      and 17 and monosomy of chromosomes 1, 7, 9, 10, and 17. In five of eight
      dysplastic oral leukoplakia biopsies, aberrations were seen consisting of trisomy
      of chromosome 1, 7, and 17, and monosomy of chromosome 9. No aberrations were
      found in biopsies of hyperplastic lesions (n = 8), or in oral cell smears of
      persons at risk. Because numerical chromosomal aberrations seem to be highly
      specific for malignant cells, FISH may help to identify leukoplakias that have a
      high risk of malignant conversion.

PMID- 9628511
TI  - Frequent mutation of p16 in squamous cell carcinoma of the head and neck.
AB  - RNA was isolated from 22 squamous cell carcinomas (SCCs) obtained from diverse
      sites within the head and neck and from matched normal tissue where available.
      Tissue samples were then screened for expression of RNA from tumor suppressor
      gene p16 by utilizing semiquantitative reverse transcriptase polymerase chain
      reaction (RT-PCR) analysis. p16-Specific PCR amplification products generated
      from tumor samples were subject to further analysis by direct DNA sequencing to
      determine if any tumor sample harbored a p16 mutation. The results show the
      presence of mutations in 10 of 22 (45%) of the tumor samples. Mutations comprise
      two identical point mutations, two small deletions (1 bp and 2 bp), one single
      nucleotide insertion, four larger deletions, and an insertion/deletion. No
      mutations in p16 have been identified by analysis of PCR products generated from
      normal matched tissue, suggesting that p16 alterations are generated by somatic
      mutation and are not germline in origin. All 22 samples were analyzed
      additionally by immunohistochemistry for nuclear expression of the retinoblastoma
      (RB) tumor suppressor gene product. Results show lack of RB nuclear expression in
      only one sample, suggesting that mutation of RB is an infrequent event in the
      development of SCC of the head and neck (SCCHN).

PMID- 9628513
TI  - A staging system for assessing severity of disease and response to therapy in
      recurrent respiratory papillomatosis.

PMID- 9628512
TI  - Tracheal autotransplantation: a reliable reconstructive technique for extended
      hemilaryngectomy defects.
AB  - OBJECTIVES: Current surgical treatment for a glottic cancer with significant
      subglottic extension is a total laryngectomy. The objective of this study was to
      expand laryngeal conservation procedures by using a reconstructive technique that
      allows for the repair of hemicricolaryngectomy defects. STUDY DESIGN: After
      resection of the ipsilateral thyroid, cricoid, and arytenoid for advanced T3
      glottic cancer, the laryngeal defect was reconstructed by means of an
      autotransplanted segment of trachea in four patients. The reconstruction
      consisted of a transferable patch that was constructed from a segment of
      revascularized cervical trachea. METHODS: During a 14-day period, a 4-cm segment
      of cervical trachea was wrapped by a free radial forearm fascial flap. In the
      second stage, the glottic cancer was removed and the cervical trachea was
      isolated on its fascial blood supply and transformed into a patch that was used
      to repair the extended hemilaryngectomy defect. Two different patch designs were
      used. Two patients underwent reconstruction with a patch augmented at the glottic
      level (group A); two patients underwent reconstruction without glottic
      augmentation on the patch (group B). Tracheal continuity was restored by an end
      to-end reanastomosis. The postreconstruction morphology of the two patch designs
      was compared with the preoperative laryngeal morphology. RESULTS: The
      autotransplantation technique led to complete restoration of the subglottic
      airway lumen in all four patients. Although the anterior-posterior glottic
      diameter was reduced by 36% in group A patients and by 43.5% in group B patients,
      a sufficient glottic airway lumen was obtained. The glottic sphincteric function
      was restored in both groups. CONCLUSIONS: Tracheal autotransplantation may be
      used reliably to repair hemicricolaryngectomy defects. Augmentation of the patch
      at the level of the glottis is not essential for successful rehabilitation.

PMID- 9628515
TI  - Fold-down thyroplasty: a new approach for congenital lateral saccular cysts.

PMID- 9628514
TI  - Repair of a high-output chylous fistula with a free fat graft.

PMID- 9628516
TI  - Improved ergonomics for bedside tracheostomy.

PMID- 9628517
TI  - Osteosarcoma of the head and neck: meta-analysis of the nonrandomized studies.

PMID- 9628518
TI  - Molecular action of GnRH analogues on ectopic endometrial cells.
AB  - The mechanisms leading to the occurrence and progression of endometriosis are far
      from being completely understood. After implantation or differentiation of
      ectopic endometrium, further proliferation of the endometriosis implants will
      depend either on the endocrine status or on the local production of endocrine,
      immunological, growth and angiogenic factors. GnRH receptors as well as GnRH
      analogues binding to cell membranes have been detected on human breast, ovarian
      and endometrial cancer cells. Thus, along with an indirect effect due to
      hypoestrogenism, a direct effect of GnRH analogues on both breast, ovarian and
      endometrial cancer cells has been suggested as a possible mechanism of action.
      Likewise, we speculate whether GnRH analogues may also exert a direct modulatory
      effect on endometriosis cell growth.

PMID- 9628519
TI  - How should we approach the management of pelvic pain?
AB  - Pelvic pain is a common debilitating condition. Most investigations are invasive,
      expensive and usually negative. Although a positive diagnosis of endometriosis
      justifies a recognized treatment programme, the majority of women with negative
      investigations are left without a diagnosis and often accused of psychological
      abnormalities. The reasons for the negative investigations are just as likely to
      be due to the inadequate techniques of the operator as the lack of pathological
      signs. The early use of menstrual suppression with GnRH analogue allows pain
      relief sooner in the majority of sufferers and separates those with pain related
      to the menstrual cycle, from whatever cause, from those whose pain is not related
      to pelvic physiology and who would not benefit from further medication or
      operative therapy. The majority, who have obtained relief from the analogue
      therapy, then have time to discuss alternative long-term treatments without the
      feeling of desperation that chronic monthly pelvic pain can produce.

PMID- 9628520
TI  - Benefit of GnRH analogue pretreatment for hysteroscopic surgery in patients with
      bleeding disorders.
AB  - Hysteroscopic surgery is widely used for the treatment of patients suffering from
      menorrhagia. In different studies, pretreatment of the endometrium with GnRH
      analogues (GnRH-a) prior to endometrial ablation has been reported to increase
      the success rate, as well as to reduce the menstrual blood flow, accounting for a
      significantly higher postoperative amenorrhea rate (42% in pretreated patients
      vs. 24% in those receiving no pretreatment). The aim of pretreatment is not only
      to obtain a thin endometrium but also to reduce the size and vascularization of
      myomas being treated. In our study, GnRH-a administration prior to endometrial
      ablation was shown to have the following advantages: improved hysteroscopic view,
      reduced blood loss, absorption of uterine distending fluid and higher
      postoperative amenorrhea rates. Prior to hysteroscopic myoma resection,
      pretreatment with GnRH-a may be particularly indicated for all myomas with a
      diameter of more than 3 cm and/or with an intramural portion, or for patients
      suffering from secondary anemia. GnRH-a pretreatment is thus indicated before
      endometrial ablation, and in most cases, before hysteroscopic resection of
      submucous myomas, and combined medical and surgical therapy has clear benefits in
      the treatment of bleeding disorders.

PMID- 9628521
TI  - Steroidal 'add-back' therapy in patients treated with GnRH agonists.
AB  - GnRH analogues (GnRH-a) are well established in the treatment of endometriosis.
      However, due to hypooestrogenic effects, treatment is limited to 6 months. The
      aim of this randomized, double-blind, comparative study was to evaluate whether
      symptoms and signs of hypooestrogenism, e.g. hot flushes, sweating and
      sleeplessness, could be avoided by a steroidal add-back regimen, while the
      beneficial effect of a GnRH-a on endometriosis could be maintained. In group A,
      14 patients were treated with 3.75 mg leuprorelin acetate depot per month i.m. in
      combination with 20 mg ethinyloestradiol plus 0.15 mg desogestrel orally for 3
      weeks. In group P, 13 patients received leuprorelin acetate, following the same
      schedule as in group A, and placebo. Treatment duration was 6 months. At first
      look laparoscopy (postoperatively) group A had an r-AFS score of 23.57 and group
      P of 24.23. After 6 months of treatment with leuprorelin acetate depot r-AFS
      scores had dropped to 16.14 in group A and to 6.25 in group P at second-look
      laparoscopy, achieving statistical significance in both groups (p < 0.001).
      Hypooestrogenic adverse drug reactions (e.g. hot flushes, sweating and
      sleeplessness) were more frequently reported in group P, whereas the occurrence
      of headache was comparable in both groups. Dysmenorrhoea was significantly
      reduced in both groups, whereas dyspareunia was only decreased in group P.
      Variations in laboratory values were within normal ranges and did not give any
      concern about drug safety. Loss of bone mineral density caused by the GnRH-a was
      reduced by the combined oestrogen/progestin add-back therapy. In conclusion, this
      therapy can lead to a reduction in hypooestrogenic adverse drug reactions and
      mostly preserves agonist efficacy with the chance of treatment prolongation.

PMID- 9628522
TI  - Add-back therapy: extending safety and efficacy of GnRH analogues in the
      gynecologic patient.
AB  - GnRH analogues have been demonstrated to be effective medical therapy for
      symptomatic endometriosis. The use of these agents has been limited to 6 months
      due to hypoestrogenic side effects. A variety of steroidal and nonsteroidal add
      back regimens have been used in an effort to eliminate such side effects while
      maintaining efficacy in order to enhance compliance, safety and duration such
      side effects while maintaining efficacy in order to enhance compliance, safety
      and duration of administration of these agents. Only 3 regimens have been shown
      to be efficacious in prolonging analogue use beyond 6 months by reducing
      vasomotor symptoms as well as preventing significant bone mineral density loss.
      These include daily norethindrone acetate 5 mg alone or in conjunction with
      conjugated equine estrogens 0.625 mg daily, as well as norethindrone 2.5 mg daily
      in conjunction with an organic bisphosphonate. With further investigation, such
      regimens may allow safe prolongation of GnRH analogue use without sacrificing
      efficacy in those endometriosis patients with severe pelvic pain.

PMID- 9628523
TI  - Evaluation of genetic variability and genetic distances between eight chicken
      lines using microsatellite markers.
AB  - The genetic variability and divergence of eight chicken lines were evaluated
      using nine microsatellite markers. The chicken lines included three White Leghorn
      hybrids, three Finnish Landrace lines, a Rhode Island Red line, and a broiler
      hybrid line. All the microsatellite loci were found to be polymorphic, the number
      of alleles varying from 4 to 13 per locus and 1 to 10 per line, respectively.
      Observed heterozygosities ranged from 0.00 to 0.91. The highest (0.67) and lowest
      (0.29) mean heterozygosity per line was observed in the broiler and in White
      Leghorn of Makela, respectively. Three of the microsatellite loci deviated from
      the Hardy-Weinberg equilibrium in some populations. F statistics indicated
      clearly the subdivision of the total population into different lines. The genetic
      distances confirmed the classification of Finnish Landraces into different lines.
      A phylogenetic consensus tree was constructed from resampled data (1,000 times)
      using the neighbor-joining method. According to the phylogenetic tree, the lines
      were grouped into three clusters, in which the White Leghorns formed one group,
      two Landraces a second group, and a Landrace, the Rhode Island Red, and the
      broiler lines a third group. Allele distribution at the loci does not support
      either the stepwise or the infinite alleles mutation model, but the distribution
      pattern was quite irregular at different loci.

PMID- 9628524
TI  - Body weight and egg weight dynamics in layers.
AB  - The association between body weight-age and egg weight-age patterns was studied
      in a segregating population of laying hens belonging to the F3 generation of a
      Rhode Island Red x White Leghorn reciprocal cross. Body weight and egg weight
      were expressed as a function of time using the model developed by Weatherup and
      Foster. Each hen was characterized in terms of its asymptotic body weight (ABW),
      maturing rate for body weight (MBW), asymptotic egg weight (AEW), and maturing
      rate for egg weight (MEW) values. Four groups of hens were distinguished by means
      of a principal component analysis. Birds belonging to Groups 1 and 3 were
      discriminated for their egg weight-age pattern. Group 1 included hens laying the
      heaviest eggs (AEW = 66.1 g) at the lowest maturing rate (MEW = 0.922), the
      inverse being true for birds in Group 3 (AEW = 55.7 g and MEW = 0.737). Birds
      belonging to Groups 2 and 4 were distinguished for their body weight-age pattern.
      Hens in Group 2 showed the lowest ABW (1,893 g) and MBW (0.764) whereas the
      heaviest (ABW = 2,802 g) and less mature (MBW = 0.929) birds were found in Group
      4. The results confirm the partial pleiotropic basis of the body weight-egg
      weight correlation, evincing the feasibility of applying selective pressure not
      only on each character separately but also on maturing rate independently of
      asymptotic weight within each trait. This strategy could be implemented using a
      biological selection index based on principal component analysis equations.

PMID- 9628525
TI  - Estimated heritability of the resistance to cecal carrier state of Salmonella
      enteritidis in chickens.
AB  - Previously, we have shown differences in susceptibility to the cecal carrier
      state in chicks orally infected with Salmonella enteritidis (SE) at 1 wk of age
      for four outbred lines: L2, B13, PA12, and Y11. The egg-type line L2 was one of
      the most susceptible lines and presented a large variability in cecal SE
      colonization. The heritability (h2) of the resistance to SE colonization in ceca
      was estimated in L2 chickens to determine whether genetic factors might be
      involved in its control. In three independent trials, a total of 819 L2 chicks
      produced from 88 sires and 232 dams were challenged orally with SE at 1 wk of
      age. Each week after inoculation, the frequency of cecal colonization was
      estimated. When this value had fallen to 50%, all the remaining animals were
      killed. The extent of cecal colonization by SE was estimated directly by counting
      the viable organisms in organs and determining the numbers of positive ceca.
      Enrichment culture was used in Trials 2 and 3. The effects of trial, of room
      within trial, and of cage within room on the frequency of SE contaminated ceca
      were often significant. No significant effect of sex was observed. Estimation of
      h2 using the frequency of SE positive ceca was low, 0.06 +/- 0.07, when results
      of direct culture were considered. In contrast, when considering the frequency
      obtained after enrichment, the h2 was estimated at 0.20 +/- 0.12. This result
      suggests a genetic basis for the expression of the resistance to colonization. An
      experiment of selection for resistance to SE carrier state in the chicken ceca
      should definitively confirm the genetic origin of the resistance.

PMID- 9628526
TI  - Genetic diversity of commercial turkey primary breeding lines as estimated by DNA
      fingerprinting.
AB  - The genetic diversity of primary breeding sire and dam lines from the three
      largest turkey breeders was estimated by band sharing of DNA fingerprints and by
      genetic distance estimated from band sharing. For comparison, experimental lines
      selected for increased egg production (E line) or increased 16-wk body weight (F
      line) were also included in the analysis. Eighteen individual DNA samples per
      line were digested with HaeIII restriction enzyme and hybridized with Jeffreys'
      33.6 probe. The DNA fingerprints were analyzed with computer programs designed to
      measure band sharing. Within commercial lines, band sharing ranged from 0.370 to
      0.508 and was greater in commercial sire lines (average = 0.475) than in
      commercial dam lines (average = 0.393), indicating that accumulated inbreeding
      was greater in the sire lines. Band sharing in the F and E lines was 0.479 and
      0.522, respectively. The average band sharing among lines was higher for primary
      breeding sire lines (average = 0.267) than for primary breeding dam lines
      (0.207), suggesting more genetic diversity in the dam lines. Genetic distance
      estimated from band sharing was greater among commercial dam lines than
      commercial sire lines. Based on band sharing between lines and genetic distance
      estimates, it appears that the experimental E and F lines contain genetic
      variation not found in the commercial lines. The results of the present study,
      along with data published in the literature, suggest that commercial primary
      breeding turkey lines are as diverse, if not more diverse, than similar
      commercial chicken lines.

PMID- 9628527
TI  - Research notes: Prevalence of selected microbial pathogens in processed poultry
      waste used as dairy cattle feed.
AB  - Processed poultry litter intended for dairy cattle feed was collected on 13 dairy
      ranches in the San Joaquin Valley of California and analyzed for the presence of
      significant bacterial pathogens associated with clinical disease in cattle or
      foodborne disease in humans. Litter samples were collected from the surface and
      interior of the litter piles upon arrival on the dairies and 2 to 4 wk later.
      Litter samples were cultured for Salmonella, Escherichia coli, Campylobacter, and
      other bacteria. The temperature of the litter piles was obtained on the surface
      and interior at each sampling. Dry matter was determined for each sample. No
      Salmonella, E. coli O157, or Campylobacter was identified (n = 104). Other E.
      coli strains were found in 8 out of 52 samples on arrival and 4 out of 52 samples
      at 2 to 4 wk after arrival. Although the surface and interior temperatures of the
      litter pile were different (23 C vs 50 C, respectively), the mean temperatures
      did not significantly change with time on the ranches. Average dry matter content
      did not differ between samples. In conclusion, the pathogens under investigation
      were not detected in processed poultry litter on these California dairy ranches
      upon arrival at the dairy or 2 to 4 wk later.

PMID- 9628528
TI  - Dietary exposure of broiler breeders to aflatoxin results in immune dysfunction
      in progeny chicks.
AB  - Broiler breeder hens were fed diets amended with 0 and 10 mg/kg (Trial 1) or 0,
      0.2, 1, or 5 mg/kg (Trial 2) of aflatoxin (AF). Fertile eggs collected during 14
      d of AF feeding were examined for AF residues. Various immunological endpoints
      were examined in chicks hatched from these eggs. Eggs collected at 7 d of AF
      feeding (Trial 1) had 0.15 to 0.48 ng/g of AFB1 and 0.22 to 0.51 ng/g of
      aflatoxicol, whereas eggs collected at 14 d of AF feeding had 0.05 to 0.60 ng of
      AFB1/g and 0.19 to 1.20 ng of aflatoxicol/g. In both trials, AF dietary exposure
      resulted in embryonic mortality and reduction in hatchability compared to
      controls. The AF progeny chicks in Trial 2 had total anti-SRBC antibodies similar
      to the controls during the primary antibody response. However, at 5 and 7 d after
      secondary SRBC injection, the antibody levels in the 1 and 5 mg/kg AF groups were
      lower than those of controls. Depression in anti-Brucella abortus antibodies
      occurred only in chicks from the 5 mg/kg AF group. Furthermore, phagocytosis of
      SRBC and reactive oxygen intermediate production by macrophages from AF progeny
      chicks were reduced as compared with the control chicks. The findings of this
      study imply that the progeny chicks from hens consuming a AF-amended diet may be
      increasingly susceptible to disease owing to suppression of humoral and cellular
      immunity.

PMID- 9628529
TI  - Nutritional aspects of hydrogenated and regular soybean oil added to diets of
      broiler chickens.
AB  - The objective of the present study was to evaluate the effect of degree of
      saturation of fat incorporated into broiler diets on performance and body fatty
      acid (FA) profile. The various degrees of saturation were achieved by using
      regular soybean oil (SO) and hydrogenated soybean oil (HSO), mixed at different
      proportions. The work was carried out on commercial broilers (Experiment 1) and
      on lines of chickens divergently selected for high (HF) or low (LF) abdominal fat
      (Experiment 2). Daily BW gain and gain:feed ratio increased and the amount of
      feed intake decreased as the dietary fat saturation decreased. Digestibility of
      total fat and of each of the FA was lowest in the HSO group and reached maximal
      values when 23% or more of the added oil was SO. The AMEn values of the diets
      were almost parallel to fat digestibility. The performance of the HF and LF
      chickens was affected by the degree of saturation similarly to that observed for
      the commercial stock. The degree of dietary fat saturation had very little effect
      on saturated FA (C16:0 and C18:0) in body lipids, reduced the level of monoenoic
      FA (C16:1 and C18:1), and raised that of polyunsaturated FA (PUFA) (C18:2, C18:3,
      and C20:4). Monoenoic FA were higher, whereas PUFA were lower in the HF than in
      the LF line. The improved AMEn in diets containing unsaturated fat is probably
      due to higher fat digestibility, direct deposition of PUFA in body lipids, and
      lower lipogenesis, associated with lower heat production.

PMID- 9628530
TI  - Diphasic allometric growth of some skeletal bones and the digestive tract in
      White Leghorn pullets consuming ad libitum and restricted diets.
AB  - Growth data of some bones (shank, tibia, and keel) and the digestive tract in
      White Leghorn pullets, which consumed ad libitum and restricted diets, were
      analyzed by mono- and diphasic allometric functions. Fat-free plucked empty body
      mass (FFEBM) or a functional entity was used as the independent variable in the
      equations. Pullets had been fed a low-lysine diet or a daily restricted amount of
      an adequate diet, from 0 to 6 or 7 to 18 wk of age. An additional group of
      pullets consumed ad libitum a control starter and grower diet. Relative growth of
      the skeletal bones and parts of the digestive tract, vs FFEBM, was described most
      accurately by a diphasic model. For each constituent, allometric slopes of the
      first growth phase (beta1) vs FFEBM were smaller than 1 (beta1 varied from 0.39
      to 0.43 for shank and tibia, from 0.48 to 0.73 for the keel, from 0.89 to 0.98
      for the total digestive tract, and from 0.80 to 0.84 for the gizzard,
      separately). These results suggest that each of the assessed organs matured
      earlier than the FFEBM. Except for the keel, which grew relatively faster than
      FFEBM if an early nutrient restriction had been applied, beta1 of all other
      assessed structures was similar for all treatments. If the allometric slope of
      the second growth phase (beta2) was estimated to be not different from zero, then
      the breakpoint between both phases was defined as the moment of attainment of
      maturity for the respective constituent. The attainment of maturity of the
      different body structures confirmed the classical growth sequence studies of the
      Hammond School. No differences in mature weights for the assessed organs between
      the feeding regimens were observed. The results indicated that in studies in
      which a nutritional deficiency had been applied, the weights of several body
      structures, most often expressed in terms of weight per 100 g BW, are strongly
      related to the decrease in growth rate of the fat-free body. It was concluded
      that most of the reported effects on growth retardation as a result of nutrient
      restrictions are primarily a consequence of the mobilization of fat per se.

PMID- 9628531
TI  - Effect of raw material source, processing systems, and processing temperatures on
      amino acid digestibility of meat and bone meals.
AB  - Experiments were conducted to evaluate amino acid digestibility of 32 commercial
      meat and bone meals (MBM) varying in raw material source and produced in seven
      different commercial cooking systems and at two processing temperatures (low vs
      high) that differed by 15 to 20 C. Raw material sources included all beef, all
      pork, mixed species, and high bone MBM. True digestibilities of amino acids were
      determined using the precision-fed cecectomized rooster assay. Protein efficiency
      ratio (PER) of six MBM varying greatly in amino acid digestibility was determined
      with chicks fed 10% CP diets containing a MBM as the sole source of dietary
      protein. The 32 MBM samples averaged 53.2% CP, 2.73% Lys, 0.6% Cys, and 0.75% Met
      on a DM basis. True digestibility averaged 82% for Lys, 87% for Met, and 47% for
      Cys. True digestibilities of amino acids varied substantially among processing
      systems and temperatures, particularly for Lys and Cys. For example, Lys and Cys
      digestibility ranged from 68 to 92% and from 20 to 71%, respectively, among
      different MBM. The higher processing temperature generally yielded lower amino
      acid digestibility than did the low processing temperature. A smaller, less
      consistent, effect was observed for raw material source. The PER values of the
      six selected MBM varied from 0.97 to 2.68 and were highly correlated with amino
      acid digestibility. These results indicated that very high amino acid
      digestibility MBM can be produced in commercial rendering systems. However,
      differences in processing systems and temperatures can cause substantial
      variability in amino acid digestibilities.

PMID- 9628532
TI  - Vitamin D deficiency alters the immune responses of broiler chicks.
AB  - Three experiments were conducted to test the hypothesis that a vitamin D
      deficiency alters the immune responses of female broiler chicks. The control diet
      contained 800 IU of cholecalciferol (vitamin D3)/kg and the deficient diet was
      the same except without supplemental vitamin D3. The vitamin D deficiency status
      was established on the basis of a significantly lower blood ionized calcium or
      total serum calcium (75 to 85% of the control). Vitamin D-deficient chicks also
      had lower growth rate and bone ash. In Experiment 1 at 8 d of age, and Experiment
      2 at 23 d of age, the cutaneous basophil hypersensitivity response as determined
      by the increase in interdigital skin thickness 20 h after a single injection of
      100 microg phytohemagglutinin-P was significantly depressed in vitamin D
      deficient chicks (62 to 64% of the control). Thymus weight, adjusted for body
      weight, was significantly lower in the vitamin D-deficient chicks at 24 d of age
      (61% of the control). Primary and secondary antibody responses against SRBC in
      vitamin D-deficient chicks were not different from the control. In Experiment 3,
      in 17-d-old chicks, vitamin D deficiency decreased the number of abdominal
      macrophages phagocytizing SRBC in vitro within 45 min from 14.7 to 10.1%. These
      results indicate that vitamin D deficiency depresses the cellular immune
      responses in young broiler chicks.

PMID- 9628534
TI  - The relative energy requirement of male vs female broilers and turkeys.
AB  - Three models to estimate energy requirement as a function of growth curve pattern
      were applied to controlled experimental data of male vs female of broilers and
      turkeys. The share of maintenance out of total feed requirement was 55% for the
      average of the three models with major divergence due to age. Comparison of the
      ratio between actual and estimated feed consumption reveals that the relative
      energy requirement was always lower in females than in males in the range of 5 to
      10% for the three models, with an average of 7.7%. It appears, therefore, that in
      estimating the energy requirement for use in practical feeding, specific models
      should be assigned for males and females in both broilers and turkeys.

PMID- 9628533
TI  - The effects of 1,25-dihydroxycholecalciferol and phytase on the natural phytate
      phosphorus utilization by laying hens.
AB  - Two experiments were conducted to investigate the effects of supplementing a corn
      soybean layer diet with either phytase, 1,25-dihydroxycholecalciferol [1,25
      (OH)2D3], or their combination. The basal diet was formulated to contain 3.00% Ca
      and 0.33% total P. In Experiment 1, 160, 56-wk-old laying hens were randomly
      assigned to treatment groups fed either the basal diet alone or diets
      supplemented with either 600 phytase units (FTU) per kilogram feed, 5 microg 1,25
      (OH)2D3/kg feed, or their combination for an experimental period of 9 wk.
      Experiment 2 had the same design and treatment groups except that laying hens 24
      wk of age were used for 8 wk. In both experiments, phytase had a positive effect
      on BW and increased plasma dialyzable P, tibia bone ash, and phytate P retention.
      In the first experiment, the addition of phytase, 1,25-(OH)2D3, or their
      combination prevented a rapid decrease in egg production due to a Mycoplasma
      gallisepticum infection observed in hens fed the basal diet. However, no benefit
      in egg production was obtained in the second experiment. No effects on egg weight
      and egg specific gravity were observed in both experiments. These results clearly
      indicate that phytase, and to a lesser extent 1,25-(OH)2D3, can be used to
      increase the utilization of phytate P by laying hens.

PMID- 9628535
TI  - Dietary arginine and lysine ratios in Large White toms. 2. Lack of interaction
      between arginine:lysine ratios and electrolyte balance.
AB  - The effect of dietary Arg:Lys ratios and dietary electrolyte balance (DEB) on
      growth and carcass parameters of Large White toms was evaluated in one experiment
      from 8 to 20 wk of age. Growth, feed conversion, and carcass composition were
      measured. All toms received a common basal diet from 0 to 8 wk of age. At 8 wk of
      age, 600 toms were randomly placed into 40 pens (15 toms per pen). The corn
      soybean meal-based experimental diets were fed from 8 to 12, 12 to 16, and 16 to
      20 wk of age and evaluated two Arg:Lys ratios (0.98 vs 1.22) and two DEB levels
      (148 vs 202 mEq/kg of diet) in a complete factorial arrangement. All experimental
      diets were pelleted. Composite samples of protein-contributing ingredients and
      complete experimental diets were analyzed for all amino acids, CP, DM, Cl, Na,
      and K. High and low average house temperature for the 8 to 20 wk period were 19
      and 15 C, respectively. No interactions occurred between Arg:Lys ratios and DEB
      for any parameter measured except litter moisture. Increasing the Arg:Lys ratio
      improved 20-wk BW (P < or = 0.027) and 8 to 20 wk gain (P < or = 0.023).
      Feed:gain from 0 to 20 wk of age was decreased by increasing the Arg:Lys ratio
      (3.01 vs 2.94; P < or = 0.026) and by increasing the DEB (3.01 vs 2.95; P < or =
      0.045). Dietary treatments did not affect mortality. Increasing DEB decreased
      cold carcass yield (P < or = 0.020). Total breast meat yield was increased (P <
      or = 0.076) by 1% in toms fed the diets containing the 1.22 Arg:Lys ratio vs toms
      fed diets containing the 0.98 Arg:Lys ratio. Toms responded favorably to
      increasing the Arg:Lys ratio for growth, feed conversion, and breast meat yield
      independent of DEB level.

PMID- 9628536
TI  - Research notes: Effect of environmental temperature on broiler chickens subjected
      to growth restriction at an early age.
AB  - An experiment was carried out to evaluate the effect of early growth restriction
      (EGR) induced by feed restriction on the ability of male broiler chickens to
      withstand exposure to high environmental temperatures. A 2 x 4 factorial
      arrangement of treatments was employed to determine whether such an exposure
      affects the beneficial effect of EGR on performance and carcass quality. Chicks
      consumed feed ad libitum or were feed-restricted from 6 to 12 d of age (to
      achieve 60% growth of the ad libitum birds). From 4 to 8 wk of age, the chickens
      were kept in temperature-controlled chambers at 25, 30, 35 C and a diurnal cyclic
      temperature of 25:35 C. Weight gain, feed intake, and feed efficiency from 6 to 8
      wk of age (after acclimatization to the various temperatures) and BW at 8 wk of
      age were significantly (P < or = 0.05) depressed by the high temperatures (35 and
      25:35 C) compared with values observed at 25 and 30 C. Early growth restriction
      did not affect these variables. Relative heart, liver, and breast meat weights at
      8 wk of age were decreased significantly with increasing temperature. Relative
      liver weight was also decreased significantly in the EGR chicks, whereas breast
      yield was increased significantly in these birds. Relative abdominal fat pad size
      was not affected by increasing the temperature from 25 to 35 C, but it was
      significantly lower in chickens kept at 25:35 C than in those kept at 25 and 35
      C. Early growth restriction significantly reduced the size of abdominal fat.
      Because no significant interactions between EGR and ambient temperature on the
      above mentioned variables were observed during 4 to 8 wk of age, it is concluded
      that EGR can not alleviate the adverse effect of high ambient temperature on
      performance, nor can high ambient temperature obliterate the beneficial effect of
      EGR in improving feed efficiency and reducing fattening.

PMID- 9628537
TI  - Influence of guanidination on apparent ileal amino acid digestibility in some
      protein sources for broilers.
AB  - High pH employed during the guanidination process (conversion of lysine residues
      to homoarginine) and its possible effects on racemization of amino acid residues
      to D-forms and on amino acid digestibility are concerns often raised with the use
      of guanidinated proteins to estimate endogenous amino acid losses in monogastric
      animals. The objective of the present study was to investigate the influence of
      guanidination on apparent ileal amino acid digestibility of casein, soybean meal,
      cottonseed meal, and canola meal for broiler chickens. Apparent ileal
      digestibility of amino acids in guanidinated and unreacted proteins, with few
      exceptions, were found to be remarkably similar. These results suggest that the
      guanidination process has no influence on the susceptibility of proteins to
      proteolysis and that racemization is not a practical problem when the proteins
      are guanidinated at low temperatures.

PMID- 9628538
TI  - Soybeans transformed with a fungal phytase gene improve phosphorus availability
      for broilers.
AB  - Male broilers (n = 416) were used to compare the efficacy of providing dietary
      phytase either as a commercial supplement or as a recombinant protein in
      transformed soybean. From 7 to 21 d of age, broilers were fed a basal diet
      containing 0.20% nonphytate P (nP) with additional supplementation by fungal
      phytase as Natuphos or as raw transformed soybeans expressing recombinant phytase
      at 400, 800, or 1,200 U/kg. For comparison, broilers were also fed the basal diet
      containing 0.08, 0.16, or 0.24 added nP. The basal diet was fed as the negative
      control. Diets were consumed ad libitum as a mash. All excreta were collected
      from each pen from 18 through 20 d of age, and the birds were killed at 21 d of
      age. Supplementing the basal diet with nP linearly increased body weight gain,
      feed efficiency, feed intake, toe ash weight and percentage, and tibia shear
      force and energy. Phosphorus digestibility decreased linearly as nP level
      increased, but P excretion increased. Dietary phytase linearly increased growth
      rate, feed intake, toe ash weight and percentage, tibia shear force and energy,
      and P digestibility, whereas excretion was decreased. Except for P digestibility,
      there was no difference in efficacy of responses for performance, bone
      mineralization, and P excretion between the two sources of phytase. It appears
      from this study that phytase can improve growth performance of broilers fed low
      nP diets when provided either as a commercial supplement or in the form of
      transformed seeds.

PMID- 9628539
TI  - Plasma testosterone profiles, semen characteristics, and artificial insemination
      in yearling and adult captive Mallard ducks (Anas platyrhynchos).
AB  - Testosterone profiles and semen characteristics were determined using yearling
      and adult captive wild-strain Mallard (Anas platyrhynchos) drakes. Wild-strain
      Mallard hens were artificially inseminated by modifying a technique developed for
      domesticated poultry. In both adult and yearling drakes, there was a change in
      the concentration of circulating plasma testosterone during the reproductive
      season. Testosterone concentrations increased from basal levels in March, peaked
      in April, and decreased to basal levels in May. The decrease in testosterone
      concentration to basal level was 2 wk earlier in yearlings than in adults (P <
      0.05). The decrease in testosterone concentration was associated with the onset
      of postnuptial molt. Semen volume (0.04 to 0.08 mL) and semen concentration
      (approximately 1.32 x 10(9) spermatozoa per milliliter) were not different
      between adult and yearling drakes (P > 0.05). Overall mean fertility for yearling
      and adult drakes obtained with artificial insemination was 70.4%. These results
      suggest that artificial insemination may be used successfully in the propagation
      of captive wild-strain Mallard ducks.

PMID- 9628540
TI  - Use of a sperm analyzer for evaluating broiler breeder males. 1. Effects of
      altering sperm quality and quantity on the sperm motility index.
AB  - A new instrument for assessing mammalian semen attributes, the Sperm Quality
      Analyzer, was evaluated as a potential tool for determining rooster sperm
      quality. The Sperm Quality Analyzer measures the "activity" of sperm in a semen
      sample as the sperm motility index (SMI). The SMI is defined as the number and
      amplitude of deflections in a light path per second as a result of sperm movement
      within a capillary tube. In the present study, effects of sperm concentration,
      viability, and motility on the SMI were evaluated. Peterson broiler breeder males
      (n = 40) were used as semen donors. In the initial experiment, semen was diluted
      from 2- to 25-fold and SMI readings were obtained. The SMI was very low in neat
      semen samples but increased when semen was diluted up to threefold. However, at
      dilutions greater than fivefold, the SMI decreased. Apparently, sperm
      concentration in undiluted semen is so great that sperm are unable to move freely
      within the capillary tube. Maximum SMI values were obtained at sperm
      concentrations of approximately 1 billion sperm per milliliter. When thawed, dead
      sperm were mixed with incubated, live sperm, the SMI decreased with decreasing
      sperm viability even though sperm concentration was constant. Obviously, fewer
      sperm move across the light beam as sperm mortality increases. When motile,
      aerobically incubated sperm were mixed at different rates with immotile,
      anaerobically incubated sperm samples, the SMI increased with increasing
      concentrations of motile sperm, whereas total sperm concentration was static. In
      addition, the SMI was strongly correlated with motility scores obtained by
      microscopic analysis. The Sperm Quality Analyzer provides an estimate of the
      overall quality of sperm from broiler breeder males by reflecting sperm
      concentration, viability, and motility in a single value, the SMI.

PMID- 9628541
TI  - Active immunization of Japanese quail hens with a recombinant chicken inhibin
      fusion protein enhances production performance.
AB  - The effects of active immunization against inhibin on production performance in
      female Japanese quail (Coturnix coturnix japonica) were assessed in two separate
      trials using an MBP-cINA521 fusion protein as an immunogen. The fusion protein,
      MBP-cINA521, consisted of the bacterial maltose binding protein (MBP) and a
      truncated form of the mature alpha-subunit of chicken inhibin (cINA521). MBP
      cINA1521 was constructed by: 1) excising a 521-bp PstI fragment from a chicken
      inhibin alpha-subunit cDNA (cINA6; gift of P. A. Johnson), 2) cloning this
      fragment, which encodes all but the first 11 amino acid residues of the mature
      alpha-subunit, into the pMal-c2 vector of the MBP fusion expression system, and
      3) expressing the fusion protein (MBP-cINA521) from the Escherichia coli and
      purifying it using affinity chromatography. In each trial, quail were randomly
      and equally assigned to one of two injection treatments as follows: 1) MBP
      cINA521 in Freund's adjuvant, or 2) Freund's adjuvant (vehicular controls; CON).
      All immunizations were given subcutaneously and Freund's complete and incomplete
      adjuvant were used for primary and booster injections, respectively. In Trial 1,
      birds were given a primary challenge of 0.2 mg MBP-cINA521 per bird at 25 d of
      age, followed by booster immunizations (0.1 mg MBP-cINA521 per bird) at 33, 40,
      47, 54 and 61 d of age and every 35 d thereafter. The CON birds received
      vehicular immunizations at the same time intervals. In Trial 2, birds treated
      with MBP-cINA521 received a primary challenge of 0.2 mg MBP-cINA521 per bird at
      26 d of age, followed by booster immunizations (0.1 mg MBP-cINA521 per bird)
      using the same schedule as that used in Trial 1, with the exception that no
      boosters were given after 61 d of age. The CON birds received vehicular
      immunizations at the same time intervals. Collection of production performance
      data was initiated coincident with the laying of the first egg in each trial
      (i.e., beginning at 41 and 44 d of age for Trials 1 and 2, respectively) and
      continued for 30 1-wk periods of lay. Combined data from Trials 1 and 2 indicated
      that the mean +/- SE age at first egg lay was markedly decreased (P < 0.005) in
      MBP-cINA521-treated quail (53.4 +/- 0.9 d of age) when compared to the CON (57.6
      +/- 1.3 d of age). Likewise, the mean +/- SE age at 50% egg production was
      reduced (P < 0.03) in quail immunized against inhibin (65.4 +/- 2.1 d of age)
      when compared to the CON (77.6 +/- 4.7 d of age). Total hen-day egg production
      was also higher (P < 0.05, Trial 1; P < 0.01, Trial 2) in MBP-cINA521-treated
      quail (88.7 +/- 1.4%, Trial 1; 90.1 +/- 1.2%, Trial 2) than in the CON birds
      (81.9 +/- 2.9%, Trial 1; 73.6 +/- 6.5%, Trial 2). Collectively, these findings
      provide evidence that inhibin immunoneutralization accelerated puberty and
      enhanced hen-day egg production during a 30-wk period of egg lay in Japanese
      quail.

PMID- 9628542
TI  - Research notes: Fresh and frozen pools of chicken red blood cells as substrates
      for direct polymerase chain reaction.
AB  - A method is presented for reliable use of pooled chicken blood samples for
      estimation of microsatellite frequencies by direct polymerase chain reaction
      (PCR) amplification of DNA. This method overcomes the variability of hematocrit
      values in individual chickens and eliminates the step of DNA preparation. The
      estimated frequencies of polymorphic alleles in fresh and frozen pooled blood
      samples were similar to those obtained by calculating these frequencies from the
      individual genotyping. When frozen pooled blood samples are used, pools should be
      prepared prior to their freezing.

PMID- 9628543
TI  - Mortality, size of the gonads, and ultrastructure of primordial germ cell in
      chick embryos treated with gamma-irradiation or injected with donor cells.
AB  - The effects of injection and/or gamma-irradiation prior to injection on
      mortality, size of the gonads, and ultrastructure of primordial germ cell (PGC)
      were examined after 5 d of incubation. The mortality of embryos injected with
      donor cells was significantly higher than that of control and irradiated embryos.
      All irradiated embryos were alive, although their development was delayed
      compared to those not exposed to irradiation. The size of the gonads of embryos
      injected with donor cells were similar to those of control embryos, however, the
      size of the gonads in irradiated embryos was significantly smaller than those of
      control embryos. The number of PGC in the gonads was significantly decreased by
      irradiation. There was no notable effect of irradiation or injection on the
      nuclei and cytoplasmic organelles in PGC.

PMID- 9628544
TI  - Serum levels of interleukin-6, alpha1-acid glycoprotein, and corticosterone in
      two-week-old chickens inoculated with Escherichia coli lipopolysaccharide.
AB  - The concentration of interleukin-6 (IL-6), alpha1-acid glycoprotein (alpha1-AG),
      and corticosterone (CORT) was investigated chronologically (0 h to 14 d) in the
      sera of 2-wk-old specific-pathogen-free chicks inoculated with Escherichia coli
      lipopolysaccharide (LPS). In the LPS group the IL-6 level was elevated from 1 h
      to 2 d and was the highest at 3 h. From 4 to 14 d the IL-6 level was low in the
      LPS group. In the PBS group, IL-6 was not detected except a mild increase from 1
      h to 6 h. In the LPS group, the alpha1-AG level increased from 6 h to 4 d, and
      the peak was 2 d. In the PBS group the alpha1-AG level was always low. The CORT
      level in the LPS group was higher than that of PBS group at 1 h. This study
      suggests that E. coli LPS may elevate serum IL-6 and CORT, and that IL-6 and CORT
      may increase the alpha1-AG level in the chicks.

PMID- 9628545
TI  - Effects of dietary vitamin E supplementation on lipid oxidation and volatiles
      content of irradiated, cooked turkey meat patties with different packaging.
AB  - A study was conducted to determine the effects of dietary vitamin E
      supplementation on the storage stability and volatiles production in irradiated
      cooked turkey meat. Turkeys, raised with diets containing 25, 50, 75, or 100 IU
      of dl-alpha-tocopheryl acetate (TA)/kg diet from 1 to 105 d of age, were fed with
      diets containing 25, 200, 400, or 600 IU of TA/kg diet from 105 to 122 d of age.
      Breast and leg meat patties were prepared, irradiated at 0 or 2.5 kGy dose,
      cooked to an internal temperature of 78 C, and stored in either vacuum or aerobic
      packaging. Thiobarbituric acid reactive substance (TBARS) values gradually
      decreased as the dietary TA increased and > 200 IU TA/kg diet treatments were
      helpful in maintaining low TBARS values in irradiated breast and leg meat patties
      during the 7-d storage period. With vacuum-packaging, irradiated cooked breast
      patties developed more oxidation than nonirradiated patties but the prooxidant
      effect of irradiation in cooked leg meat patties was not consistent. In aerobic
      packaged cooked meat, irradiated patties had lower TBARS than nonirradiated
      patties in both breast and leg meat stored in oxygen permeable bags for 7 d.
      Propanal, pentanal, hexanal, 1-pentanol, and total volatiles were highly
      correlated with the TBARS values of meat. However, hexanal represented the lipid
      oxidation status of cooked meat better than any other volatiles component. The
      amount of hexanal and total volatiles in cooked breast and leg meat shows
      decreasing trends as dietary TA increased. In vacuum packaging, irradiated breast
      and leg meat had higher hexanal and total volatiles content than nonirradiated
      meat at both 0 and 7 d of storage. In aerobic packaging, the amount of hexanal
      and total volatiles greatly increased in both irradiated and nonirradiated meat
      patties during the 7-d storage periods. The results illustrated that the
      antioxidant effect of TA was not strong enough to control lipid oxidation and off
      odor generation in cooked meat stored under aerobic conditions because the
      progress of lipid oxidation in cooked meat under aerobic condition is very rapid.
      However, the combination of dietary TA and vacuum packaging of cooked meat
      immediately after cooking could be a good strategy to minimize oxidation and
      volatiles production in cooked meat.

PMID- 9628546
TI  - The selective estrogen receptor modulator, raloxifene: an overview of nonclinical
      pharmacology and reproductive and developmental testing.
AB  - Raloxifene is a nonsteroidal, selective estrogen receptor modulator being
      developed by Eli Lilly and Company as a therapeutic agent for postmenopausal
      osteoporosis. In the ovariectomized (OVX) rat, raloxifene prevents the loss of
      bone at the distal metaphysis of the femur, proximal tibia, and vertebrae;
      reduces cancellous bone resorption; and reduces serum cholesterol, but does not
      cause any significant changes in stromal eosinophilia or uterine epithelium. In
      estrogen-stimulated OVX rats, raloxifene prevents the morning lowering of serum
      luteinizing hormone levels, produces a reduction in afternoon serum prolactin
      levels, antagonizes pituitary weight increase, and antagonizes stimulation of
      mammary gland development. Raloxifene also has been shown to exhibit
      antiestrogenic activity in several in vivo and in vitro mammary tumor models.
      Raloxifene treatment results in regression of endometriosis in both a surgically
      prepared, rat uterine explant model and in Rhesus macaques diagnosed with
      spontaneous endometriosis before exposure. Also, uterine leiomyomas in estrogen
      stimulated OVX guinea pigs regress after the onset of raloxifene treatment.
      Raloxifene antagonizes testosterone-induced increases in prostate weight of
      castrated rats, but does not bind to androgen receptors or affect prostatic 5
      alpha-reductase or testicular steroid 17-alpha-hydroxylase activity. A series of
      preclinical toxicology studies was designed to characterize reproductive and
      developmental outcomes following various schedules of raloxifene treatment in
      rats or rabbits. Studies of female reproduction and developmental outcome were
      conducted primarily at pharmacologic doses (0.1, 1, or 10 mg/kg/d); male
      reproductive studies used higher doses (10, 30, or 100 mg/kg/d). In this series
      of studies, male reproductive end points were not affected, whereas embryo
      implantation, fetal rabbit morphology, and several aspects of offspring
      development were disrupted by the lowest dose of maternal raloxifene treatment, a
      profile consistent with estrogen antagonist activity.

PMID- 9628547
TI  - The selective estrogen receptor modulator, raloxifene: reproductive assessments
      in adult male rats.
AB  - Raloxifene HCl is a nonsteroidal, selective estrogen receptor modulator developed
      for postmenopausal osteoporosis. Reproductive toxicity of raloxifene was examined
      in adult male CD rats after the oral administration of doses of 0, 10, 30, or 100
      mg/kg/d. In the first study, males (12/group) were treated for 2 weeks followed
      by 2 weeks without treatment. After dose administration on Day 13, 6 males/group
      were cohabited with untreated females (1:2) for up to 7 d. Males were killed on
      Day 14 or 28 (6/group each day). Sperm were collected from the right cauda
      epididymis and evaluated for relative concentration, motion characteristics, and
      breakage. The kinetics of spermatogenesis were examined by DNA flow cytometry.
      The left testis and epididymis were preserved for histopathologic evaluation.
      Females were examined for reproductive status on Gestation Day 13. In a second
      study, males (20/group) were treated for 7 weeks (4 weeks prior to cohabitation
      during a 2-week cohabitation period, and for 1 additional week). Treated males
      were cohabited with untreated females (1:1). On Gestation Day 20, untreated
      females were examined for reproductive status and fetuses were examined for
      viability, weight, gender, and morphology. At necropsy, male reproductive tissues
      were collected, weighed, and preserved for histopathologic evaluation. In both
      studies, male body weight gain and food consumption were depressed at all dose
      levels. There was no indication in either study that raloxifene caused important
      changes in sperm production, sperm quality, or male reproductive performance at
      doses as high as 100 mg/kg/d.

PMID- 9628548
TI  - The selective estrogen receptor modulator, raloxifene: reproductive assessments
      following premating exposure in female rats.
AB  - Raloxifene HCl is a nonsteroidal, selective estrogen receptor modulator developed
      as a therapeutic agent for postmenopausal osteoporosis. Two studies were
      conducted that examined the effects of premating exposure to raloxifene HCl. In
      the first study, adult female CD rats (20/group) were given diets containing 0,
      0.01, or 0.1% raloxifene (providing an average of 0, 6, or 63 mg/kg/d,
      respectively) for 2 weeks, after which the treated diets were replaced with
      control diet. Following a 2-week period without treatment, each female that had
      displayed at least three conversions in vaginal cytology from cornified cells to
      leukocytes was cohabited for 1 to 2 d with an untreated male as she entered
      proestrus. Females were killed at midgestation and examined for evidence of
      pregnancy. In the second study, adult female CD rats (40/group) were given oral
      gavage doses of raloxifene (0, 0.1, 1, or 10 mg/kg/d) for 4 weeks. Immediately or
      following a 2-week period without treatment, 20 females/group were cohabited with
      untreated males (1:1) for up to 3 weeks. The females were allowed to deliver and
      rear their offspring until Postpartum Day 21. Progeny survival, growth, and
      development were evaluated. Maternal body weight, body weight gain, and food
      consumption were depressed in all raloxifene treatment groups. Doses > or =1
      mg/kg caused disruptions in estrous cycles. In Study 1, 90% of the females
      treated with raloxifene resumed normal cycling, and fertility was not
      significantly affected. Although there were no statistically significant
      differences in time-to-mating, fertility, or liveborn indices in Study 2, females
      in the 10-mg/kg immediate-cohabitation group had slightly increased gestation
      lengths and smaller litter sizes. Progeny from these litters were larger on
      Postpartum Day 1 and had advanced incisor eruption and eye opening. In addition,
      slight delays were seen in physical landmark appearance in the 0.1- and 1-mg/kg
      immediate-cohabitation groups and in the 1- and 10-mg/kg delayed-cohabitation
      groups. Progeny viability, growth, and negative geotactic performance were not
      adversely affected. In these studies of maternal premating exposure to
      raloxifene, findings were consistent with established pharmacologic activity of
      the test chemical. Reproductive effects (disrupted estrous cycles and decreased
      litter size) occurred at doses > or =1 mg/kg and were generally reversible.
      Effects on offspring were seen at doses > or =0.1 mg/kg, were of minor
      importance, and were resolved during the lactation period.

PMID- 9628549
TI  - The selective estrogen receptor modulator, raloxifene: reproductive assessments
      following preimplantation exposure in mated female rats.
AB  - Raloxifene is a nonsteroidal, selective estrogen receptor modulator being
      developed for postmenopausal osteoporosis. As part of an integrated reproductive
      toxicity assessment, two studies were conducted in which raloxifene was
      administered orally to CD rats during Gestation Days (GD) 0 through 5. In each
      study, animals received daily raloxifene doses of 0, 0.1, 1, or 10 mg/kg. In
      Study 1, GD 20 evaluations of maternal reproductive parameters identified dose
      related increases in pre- and postimplantation loss, reductions in the numbers of
      corpora lutea and live conceptuses, and reduced fetal weight. The low fetal
      weights were consistent with an extent of morphologic development that
      corresponded to developmental ages up to 8 d younger than GD 20. Study 2
      characterized the potential impact of this disrupted and apparently delayed
      implantation on gestation length, parturition, and progeny viability. Dams were
      allowed to deliver and rear their offspring through Postpartum Day 21. Gestation
      lengths were extended up to 1 week, and litter sizes were reduced in a dose
      dependent manner. Nevertheless, parturition occurred normally and pup morphology,
      survival, and physical and behavioral development were unaffected.

PMID- 9628550
TI  - The selective estrogen receptor modulator, raloxifene: segment II studies in rats
      and rabbits.
AB  - Raloxifene is a nonsteroidal, selective estrogen receptor modulator developed by
      Eli Lilly and Company primarily as a therapeutic agent for postmenopausal
      osteoporosis. Two Segment II studies were conducted that examined maternal
      reproductive parameters and fetal outcome following gestational exposure to
      raloxifene. Pregnant CD rats (25/group) and New Zealand white rabbits (20/group)
      were dosed once daily by oral gavage with 0, 0.1, 1, or 10 mg/kg on Gestation
      Days (GD) 6 through 17 and 7 through 19, respectively. Maternal body weight and
      food consumption were monitored throughout pregnancy. Caesarean sections were
      performed on GD 20 and GD 28 for rats and rabbits, respectively, to evaluate
      fetal viability, weight, and morphology. In rats, maternal body weight, body
      weight gain, and food consumption were reduced in all raloxifene treatment
      groups. Fetal viability was depressed in the 10-mg/kg group and was often
      associated with signs of hemorrhaging from the vagina. Fetal growth retardation
      was indicated in the 1- and/or 10-mg/kg groups by increased incidences of fetal
      runts and the developmental deviations, wavy ribs and kidney cavitation. There
      was no evidence of treatment-related malformations in rat fetuses. In rabbits,
      depressions in body weight gain and food consumption occurred in the 10-mg/kg
      group, and a single abortion occurred in the 1-mg/kg group. Fetal viability and
      weights were not affected in any of the raloxifene treatment groups. The overall
      proportions of fetuses with malformations, deviations, or variations were not
      affected by treatment with raloxifene; however, one fetus each from the 0.1-, 1-,
      and 10-mg/kg groups had incomplete closure of the interventricular septum.
      Therefore, maternal and fetal no-effect levels were not obtained in this study of
      raloxifene.

PMID- 9628551
TI  - The selective estrogen receptor modulator, raloxifene: a segment II/III delivery
      study in rats.
AB  - Raloxifene is a nonsteroidal, selective estrogen receptor modulator developed by
      Eli Lilly and Company as a therapeutic agent for postmenopausal osteoporosis.
      Raloxifene was administered orally by gavage at doses of 0, 0.1, 1, or 10 mg/kg/d
      to female CD rats (25/group) on Gestation Day 6 (GD 6) through Postpartum Day 20
      (PD 20). Females were allowed to deliver and maintain their progeny until PD 21.
      All dead pups and pups culled on PD 1 were given internal and external
      examinations. One pup/sex/litter was assigned to each of the following assessment
      groups: 1) the primary pair for the F1 generation study, in which survival,
      growth, development, behavior, indicators of sexual maturation, and reproductive
      performance were evaluated; 2) terminal necropsy evaluations at PD 21; 3)
      terminal necropsy evaluations at 60 d of age; and 4) assessments of immune
      function at 5 to 6 weeks of age. At termination on PD 21, 60, or approximately
      140, a necropsy was performed; crown rump and tibia lengths were measured;
      pituitary weights were taken; and a portion of the anterior pituitary was
      retained for growth hormone, luteinizing hormone, and prolactin content
      determinations (control and 10-mg/kg groups only). The remainder of the pituitary
      and reproductive tissues were retained for histologic evaluations. Dose-related
      depressions in maternal body weight and food consumption occurred during
      gestation. Mean gestation length was increased at 1 and 10 mg/kg. Delayed,
      extended, and/or disrupted parturition occurred in dams given 10 mg/kg, which
      resulted in a high incidence of maternal morbidity and/or death, increased
      numbers of dead pups, and the survival of only 66% of live pups to PD 21. Progeny
      body weights were not decreased at birth, but were depressed progressively in a
      dose-related manner during the 3-week lactation period. Negative geotaxis and
      incisor eruption were apparently accelerated in the 1- and 10-mg/kg groups, but
      eye opening was delayed at 10 mg/kg. Postweaning activity levels, auditory
      startle, and passive avoidance performance were not affected in the raloxifene
      groups. Dose-related decreases in spleen cellularity and thymus weights occurred
      in both sexes, but immune system function, as measured by splenic natural killer
      cell activity and antibody response to sheep red blood cells, was not affected.
      Postweaning body weights and growth parameters, as well as pituitary hormone
      content, were affected in both an age- and sex-specific manner. Preputial
      separation was not affected, but vaginal patency occurred ca 2 d earlier than
      controls in females from the 10-mg/kg group. Estrous cycles of the F1 females
      were not affected during the first two weeks after vaginal opening, but were
      disrupted at 12 to 14 weeks of age in the 10-mg/kg group. These females showed
      poorer mating and fertility indices, and litter size was reduced in the two
      females that were pregnant. Histologically, reproductive organs were not affected
      in males at any age or in females at PD 21. At PD 60, vaginal mucification
      occurred in females from the 0.1- and 1-mg/kg groups. At PD 140, the only finding
      was a high rate of uterine hypoplasia in the 10-mg/kg group, and this finding
      occurred in the absence of any concomitant ovarian or vaginal changes. These
      reproductive and developmental findings are consistent with estrogen antagonist
      activity of raloxifene.

PMID- 9628552
TI  - Caffeine intake and fecundability: a follow-up study among 430 Danish couples
      planning their first pregnancy.
AB  - Fecundability has been defined as the ability to achieve a recognized pregnancy.
      Several studies on caffeine and fecundability have been conducted but have been
      inconclusive. This may be explained partly by lack of stratification by smoking.
      Furthermore, few researchers have tried to separate the effect of caffeine from
      different sources (coffee, tea, cola, and chocolate). Clearly, the relationship
      between caffeine and fecundability needs further research, given the high
      prevalence of caffeine intake among women of childbearing age. We examined the
      independent and combined effects of smoking and caffeine intake from different
      sources on the probability of conception. From 1992 to 1995, a total of 430
      couples were recruited after a nationwide mailing of a personal letter to 52,255
      trade union members who were 20 to 35 years old, lived with a partner, and had no
      previous reproductive experience. At enrollment and in six cycles of follow-up,
      both partners filled out a questionnaire on different factors including smoking
      habits and their intake of coffee, tea, chocolate, cola beverages, and chocolate
      bars. In all, 1596 cycles and 423 couples were included in the analyses. The
      cycle-specific association between caffeine intake and fecundability was analyzed
      in a logistic regression model with the outcome at each cycle (pregnant or not
      pregnant) in a Cox discrete model calculating the fecundability odds-ratio (FR).
      Compared to nonsmoking women with caffeine intake less than 300 mg/d, nonsmoking
      women who consumed 300 to 700 mg/d caffeine had a FR of 0.88 [95% confidence
      interval (CI) 0.60-1.31], whereas women with a higher caffeine intake had a FR =
      0.63 (95% CI 0.25-1.60) after adjusting for female body mass index and alcohol
      intake, diseases of the female reproductive organs, semen quality, and duration
      of menstrual cycle. No dose-response relationship was found among smokers. Among
      males, the same decline in point estimates of the FR was present. Smoking women
      whose only source of caffeine was coffee (>300 mg/d) had a reduced fecundability
      odds-ratio (FR = 0.34; 95% CI 0.12-0.98). An interaction between caffeine and
      smoking is biologically plausible, and the lack of effect among smokers may be
      due to faster metabolism of caffeine. Our findings suggest that especially
      nonsmoking women who wish to achieve a pregnancy might benefit from a reduced
      caffeine intake.

PMID- 9628553
TI  - An assessment of fertility in boron-exposed Turkish subpopulations.
AB  - Relationships between elevated boron intake and fertility were sought by
      comparing reproduction in the residents of two Turkish villages with high levels
      of boron in their drinking water (one with 8.5 to 29 mg B/L and the other with
      2.05 to 2.5 mg B/L), with three nearby villages with more typical low boron
      levels (0.03 to 0.40 mg B/L). The two high boron villages were designated as
      Region I, and the three villages with low boron in the drinking water were
      designated Region II. In addition to exposure to elevated boron in drinking
      water, 28.3% of the probands in Region I were employed in borate mining or
      processing, whereas in Region II, 11.7% were so employed. An observational study
      was carried out in which the authors compared the reproductive history of
      families living in Region I with families living in Region II by identifying
      married adults (referred to as probands) who were able to provide information
      about their and their spouses' family pedigrees covering three generations.
      Probands were identified by home visits and, if ever married, accepted for
      ascertainment. Evidence of fertility was birth of a living child, and data were
      obtained about the fertility of the proband generation, their parents' and also
      their childrens' generations. In high-boron villages (Region I), 159 three
      generation kindreds containing 1068 families were ascertained and, in low-boron
      villages (Region II), 154 three-generation kindreds containing 610 families were
      ascertained. In Region 1, 96% of marriages produced at least one child, with
      primary infertility estimated at 2.34% compared with 96% and 2.62%, respectively,
      for Region II. There was no significant difference in fertility either between
      Region I and Region II or between the villages within the Regions. The fertility
      figures are not different from similar measures of fertility in other parts of
      Turkey. In Region I, the gender ratio (M:F) of offspring was 0.89, whereas in the
      Region II villages the gender ratio was 1.04 (NS, chi2 = 1.335, P > 0.05). It is
      concluded that at the elevated boron drinking water levels studied, a boron
      related effect on reproduction was not found.

PMID- 9628554
TI  - The effect of photomirex on the in vitro perfused ovary of the rat.
AB  - Photomirex, a photodegradation product of the insecticide mirex, is an
      environmental contaminant that has been identified in Great Lakes fish, soil, and
      human adipose tissue. Because of the potential for human exposure, the present
      study was designed to investigate the short-term effects of photomirex on the in
      vitro perfused ovary of the rat. Adult Sprague-Dawley rat ovaries were isolated
      and perfused for a total of 6 h with Medium 199. Following a 2-h baseline period,
      10(-4) M of photomirex was administered to the medium. Control ovaries received
      medium or DMSO (vehicle control). Significant effects of perfusion and chemical
      intervention were identified using lactate dehydrogenase enzyme, glucose
      utilization, lactate, pyruvate, and flow:pressure ratio as markers of toxicity (P
      < 0.05). Lactate:pyruvate ratio, glutathione, and oxygen consumption did not
      demonstrate significant effects. Post hoc tests showed that there were
      significant differences between the DMSO + photomirex group and the control group
      (M199) using lactate dehydrogenase as a marker of toxicity. Pyruvate
      concentration was also reduced significantly after perfusion with DMSO +
      photomirex compared to M199 only and DMSO only (P < 0.05). Histopathologic
      changes were not discernible by light microscopy. These results suggest that
      metabolic and respiratory processes of the ovary are acutely sensitive to
      perturbation with photomirex in the in vitro perfused rat ovary model.

PMID- 9628555
TI  - Formamide and dimethylformamide: reproductive assessment by continuous breeding
      in mice.
AB  - Reproductive toxicity in Swiss mice, during chronic exposure to formamide (FORM)
      or dimethylformamide (DMF), was evaluated using the Reproductive Assessment by
      Continuous Breeding Protocols. FORM administered in drinking water at 0, 100,
      350, and 750 ppm (approximately 20 to 200 mg/kg/d) reduced fertility and litter
      size in F0 animals without generalized toxicity at 750 ppm FORM. Crossover
      matings suggested that females were the affected sex. After F1 mating, FORM
      reduced F2 litter size, increased days to litter, reduced relative ovarian
      weight, and lengthened estrous cycles at 750 ppm. The No-Observed-Adverse-Effect
      Level for generalized toxicity was 750 ppm for the F0 and 350 ppm for the F1
      generation. Reproductive performance was normal at 350 ppm for both F0 and F1
      mice. Chronic exposure to DMF in drinking water at 0, 1000, 4000, and 7000 ppm
      (approximately 200 to 1300 mg/kg/d) reduced fertility by the first litter at 4000
      ppm, reduced body weight in F0 females at 7000 ppm, and increased liver weights
      at all doses in both sexes. A crossover mating at 7000 ppm identified F0 females
      as the affected sex. F1 postnatal survival was reduced at > or =4000 ppm DMF. F1
      mating reduced F2 litter size and live pup weight at > or =1000 ppm. At necropsy,
      body weight of F1 males and females was reduced at > or =4000 ppm. DMF-treated
      pups (both F1 and F2) and F1 adults had cranial and sternebral skeletal
      malformations. Only DMF caused overt developmental toxicity. A No-Observed
      Adverse-Effect-Level for DMF was not established.

PMID- 9628556
TI  - Male reproductive effects of lead, including species extrapolation for the rabbit
      model.
AB  - The effects of elevated blood lead on semen quality were evaluated in the rabbit
      model and compared to published effects in humans. Mature, male rabbits were
      given lead acetate by subcutaneous injection in the dose range of 0 to 3.85 mg/kg
      on a Monday-Wednesday-Friday basis. In each of eight treatment groups, a dosing
      regimen was developed to produce blood lead levels of 0, 20, 40, 50, 70, 80, 90,
      and 110 microg/dL. A 5-week pre-exposure period was followed by a 15-week
      exposure testing period allowing for response through six cycles of the
      seminiferous epithelium. Semen analyses revealed that increased blood lead levels
      were associated with adverse changes in the sperm count, ejaculate volume,
      percent motile sperm, swimming velocities, and morphology. Hormonal responses
      were minimal. Testicular pathology revealed a dose-dependent inhibition of
      spermiation. For six measures of semen quality, threshold estimates ranged from
      16 to 24 microg/dL. Using the species extrapolation factor derived in this study,
      a rabbit dose would have to be divided by 1.56 to obtain the equivalent human
      dose for an equal percentage decrease in sperm concentration; however, rabbits
      are 3.75 more sensitive in terms of absolute decrease in sperm count for a given
      blood lead level.

PMID- 9628557
TI  - Effects of lead exposure on GnRH and LH secretion in male rats: response to
      castration and alpha-methyl-p-tyrosine (AMPT) challenge.
AB  - Animal and clinical studies suggest that lead exposure disrupts the hypothalamic
      pituitary axis. To define more precisely the toxic action of lead on the
      hypothalamic-pituitary unit, a series of in vivo and in vitro experiments were
      performed. The first experiment was designed to determine whether lead exposure
      exerts an inhibitory effect on GnRH secretion as reflected by an enhanced
      inhibition of luteinizing hormone (LH) secretion in response to the tyrosine
      hydroxylase inhibitor methyl-p-tyrosine (AMPT). In the control animals, the AMPT
      dose had no significant effect on LH secretion, whereas LH fell significantly in
      the lead-treated animals. In experiments designed to evaluate the effects of lead
      exposure on the pattern of pulsatile release of gonadotropins castrated control
      and lead-dosed animals were cannulated, and serial blood sampling was performed.
      Baseline LH and follicle-stimulating hormone values were not statistically
      different between the control and lead-treated group. There were no significant
      differences noted in pulsatile patterns when the data were analyzed as groups.
      Pituitary cells harvested from lead-treated animals released significantly more
      LH that did the control animals. These data are consistent with the hypothesis
      that the signals between the hypothalamus and pituitary gland are disrupted by
      lead exposure in the intact animal. However, the lead-exposed castrated rat's
      hypothalamic-pituitary unit is able to adapt to the toxic effects of lead.

PMID- 9628559
TI  - Postcoital antifertility activity of aminoalcohols.
AB  - Previously, postcoital antifertility effects of a number of aminoalcohols,
      including 2-(isopropylamino)-ethanol, have been demonstrated in rodents. In this
      experiment, we compared the antifertility activity of 2-(isopropylamino)-ethanol
      to the following analogs: hydroxyethylpiperidine, hydroxyethylpiridine,
      hydroxyethylpirrolidine, and hydroxyethylpirrolidone. Female rats were gavaged on
      Days 0 through 5 of gestation with 0.7 mmol/kg/d of these substances. Only 2
      (isopropylamino)-ethanol and hydroxyethylpirrolidine showed a strong
      antifertility activity: females treated with 2-(isopropylamino)-ethanol had no
      signs of implantation, whereas those treated with hydroxyethylpirrolidine had
      100% early resorptions. Treatments with these two substances during the
      periimplantation period (Days 4 and 5) produced 100% early resorptions.
      Histologic examination of the implantation sites showed signs of embryonic
      degeneration starting from Day 6.5 of gestation. The flushing of the uteri of
      females treated with 2-(isopropylamino)-ethanol on Days 0 through 3 post coitum
      showed 78% of the embryos at the stage of 1 to 3 blastomeres, whereas the embryos
      of females treated during the same period with hydroxyethylpirrolidine were
      normal blastocysts. Therefore, 2-(isopropylamino)-ethanol and
      hydroxyethylpirrolidine are able to kill embryos during the early implantation
      stages, whereas 2-(isopropylamino)-ethanol is also able to stop the development
      of preimplantation embryos.

PMID- 9628558
TI  - Mechanisms of gender-specific TCDD-induced toxicity in guinea pig adipose tissue.
AB  - After treatment with TCDD, the activities of cytosolic AhR-associated c-Src
      kinase, microsomal protein kinase C (nPKC epsilon), microsomal c-Src kinase,
      nuclear p44/42 MAPK, c-Jun N terminus kinase, and the amount of microsomal pan
      Ras protein were different in males and females. TCDD did not decrease body or
      adipose tissue weights in transgenic src-deficient male mice as compared to their
      wild-type littermates, and the activity of AhR-associated c-Src kinase was not
      increased by TCDD in src-deficient male mice. Similar results were obtained when
      TCDD was given to male guinea pigs treated with the Src-kinase inhibitor,
      geldanamycin. Treatment with estradiol protected male guinea pigs from TCDD
      induced wasting. TCDD induced similar changes in protein tyrosine kinase activity
      in adipose tissues of castrated male and intact female guinea pigs. The gender
      specific mechanisms of TCDD-induced toxicity appear to involve c-Src kinase, nPKC
      epsilon, and pan-Ras, as well as overlap in the cytosolic signal transduction
      pathways of TCDD and sex steroids.

PMID- 9628560
TI  - Embryotoxic effects of SKI 2053R, a new potential anticancer agent, in rats.
AB  - SKI 2053R, cis-malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolan e]
      platinum(II), is a newly developed antitumor platinum complex derived from
      cisplatin. Preclinical studies suggest that it may have greater antitumor
      activity and lower toxicity than cisplatin. The potential of SKI 2053R to induce
      embryotoxicity was investigated in the Sprague-Dawley rat. One hundred mated rats
      (sperm in vaginal lavage = Day 0) were distributed among three treated groups and
      a control group. SKI 2053R was administered intravenously to pregnant rats from
      Days 6 to 16 of gestation at dose levels of 0, 0.75, 1.5, and 3.0 mg/kg/d. All
      dams were subjected to caesarean section on Day 20 of gestation. At 3 mg/kg,
      reduced food intake, reduced body weight, and decreased liver weight were
      observed in dams. An increase in the resorption rate and a reduction in the fetal
      weight were also found. In addition, various types of visceral and skeletal
      malformations occurred at an incidence of 18.5 and 6.0%, respectively.
      Characteristic malformations included dilated cerebral ventricle, anophthalmia,
      microphthalmia, fused or absent cervical arch, fused thoracic arch, fused
      thoracic centrum, and fused rib, among others. Delayed ossification of both
      sternebrae and metatarsals was also observed. There were no signs of maternal
      toxicity or embryotoxicity at 0.75 and 1.5 mg/kg. The results show that SKI 2053R
      is embryotoxic at a minimally maternally toxic dose in rats.

PMID- 9628561
TI  - Pregnancy outcome in women exposed to calcium channel blockers.

PMID- 9628563
TI  - Establishment of a concordant xenogeneic splenocyte injection model for the
      dynamic study of the marginal zone in the spleen.
AB  - BACKGROUND: This study was undertaken to establish a simple technique with which
      we could investigate the relationship between the marginal zone (MZ) in the
      spleen and antispecies antibody production, as well as to estimate the efficacy
      of various immunosuppressive treatments in xenotransplantation. METHODS: With a
      concordant xenogeneic combination (hamster-to-rat), the early phase reaction of
      the MZ was studied by use of quantitative histologic analysis, and complement
      dependent cytotoxic antibody titers were determined in both a heart
      transplantation model and the splenocyte injection model. Furthermore, changes in
      the MZ were examined with isogeneic and allogeneic combinations with the
      splenocyte injection model. Next, the effect of cyclophosphamide, a promising
      immunosuppressant for concordant xenotransplantation, was examined by use of the
      splenocyte injection model. RESULTS: With a concordant xenogeneic combination,
      the MZ enlarged, and antihamster immunoglobulin M antibody synthesis increased
      after immunization in both models. On the other hand, with an isogeneic
      combination, the MZ did not expand, and with an allogeneic combination the MZ
      enlargement was not as great as that with a concordant xenogeneic combination.
      Cyclophosphamide suppressed the MZ expansion in a dose-dependent manner and
      effectively diminished antibody production in the splenocyte injection model.
      CONCLUSION: Dynamic studies of the MZ in the spleen with the splenocyte injection
      model are useful for the elucidation of the mechanisms of reaction and for
      estimating the efficacy of various immunosuppressive treatments in concordant
      xenotransplantation.

PMID- 9628562
TI  - Enhancement of obliterative airway disease in rat tracheal allografts infected
      with recombinant rat cytomegalovirus.
AB  - BACKGROUND: Cytomegalovirus infection has been identified as a significant risk
      factor for the development of obliterative bronchiolitis in human lung transplant
      recipients. This study was designed to assess the influence of rat
      cytomegalovirus (RCMV) on the pathogenesis and development of obliterative
      bronchiolitis in an experimental model of obliterative airway disease, which
      occurs after allogenic heterotopic tracheal transplantation in rodents. METHODS:
      Sixty Lewis rats were infected intraperitoneally with 10(7) plaque-forming units
      of recombinant lac-Z-tagged RCMV expressing the gene for beta-galactosidase. Rats
      were either infected at the time of surgery (acute infection, n = 30) or 56 days
      before surgery (chronic infection, n = 30). Tracheae from Brown Norway
      (allograft) or Lewis (isograft) rats were implanted and wrapped in the greater
      omentum of infected Lewis rats. RCMV infection was verified in different
      recipient tissues by in vitro plaque-assays and by direct in situ staining for
      beta-galactosidase activity. The tracheal grafts were harvested on days 7, 14,
      and 21 after transplantation and stained with hematoxylin-eosin and Masson's
      trichrome. The peritracheal cellular inflammation was scored visually. The
      cellular density of the infiltrating cells and the extent of airway obliteration
      were analyzed by use of computer-digitized morphometry and compared with
      uninfected allografts as control. RESULTS: Both acute and chronic cytomegalovirus
      infection produced significantly higher mononuclear cell density values on days 7
      and 14 compared with noninfected controls, indicating a more intense immune
      response in the infected allografts. Tracheal allograft obliteration was also
      more extensive after acute and, in particular, after chronic cytomegalovirus
      infection (64% narrowing after 21 days compared with 36% in grafts from
      noninfected control animals). CONCLUSIONS: Our experimental results provide
      direct evidence that the tracheal grafts were infected with RCMV and that the
      development of obliterative airway disease was enhanced in the acutely and
      chronically infected allografts compared with grafts from noninfected control
      animals.

PMID- 9628564
TI  - Bidirectional blockade of CD4 and major histocompatibility complex class II
      molecules: an effective immunosuppressive treatment in the mouse heart
      transplantation model.
AB  - BACKGROUND: Anti-CD4 monoclonal antibodies (mabs) are powerful immunosuppressive
      agents. However, in experimental models anti-CD4 treatment alone is not always
      completely effective. Anti-major histocompatibility complex (MHC) class II mabs
      may have a synergistic effect with anti-CD4 mab therapy by blocking the function
      of both antigen-presenting cells and T cells. METHODS: C3H/He mice (H-2k: I-Ak, I
      Ek) received a vascularized cardiac graft from C57BL/10 (H-2b: I-Ab) or BALB/c (H
      2d: I-Ad, I-Ed) mice and were treated with a depleting anti-CD4 or a depleting
      anti-MHC class II antibody either alone or in combination. RESULTS: Anti-CD4
      treatment alone prolonged graft survival in both strain combinations but was only
      minimally effective when BALB/c donors were used. However, when anti-CD4 and anti
      MHC class II mabs were administered together, graft survival was significantly
      prolonged in both strain combinations. The ratio of interleukin-4 (IL
      4)/interferon-gamma (IFN-gamma) expressed in both C57BL/10- and BALB/c
      transplanted hearts 7 days after transplantation was significantly higher after
      combined treatment with anti-CD4 plus anti-MHC class II mabs compared with that
      found after either treatment alone. Twenty-one days after transplantation, the
      ratio of IL-4/IFN-gamma in BALB/c hearts after combined mab therapy was
      significantly lower than at 7 days after transplantation, but in contrast, the
      cytokine ratio in C57BL/10 hearts remained at an elevated level during the first
      21 days after transplantation. CONCLUSIONS: These data demonstrate that
      bidirectional blockade of the antigen-presenting cell and T-cell interaction by
      use of anti-CD4 and anti-MHC class II mabs in combination is more effective than
      either treatment alone. Graft survival in this model seems to correlate with a
      prolonged elevation of the IL-4/IFN-gamma ratio in the transplanted heart,
      suggesting that in this model the induction of unresponsiveness may be associated
      with a shift toward a Th2-type T-cell response.

PMID- 9628565
TI  - Complement contributes to the rejection of complete and class I major
      histocompatibility complex--incompatible cardiac allografts.
AB  - BACKGROUND: We have demonstrated previously that the terminal complement
      component C6 contributes to the acute rejection of ACI cardiac allografts by PVG
      recipients. ACI rats differ from PVG rats at major and minor histocompatibility
      antigens and ACI cardiac allografts stimulate vigorous alloantibody responses in
      PVG rats. We have now bred the C6 deficiency onto four PVG congenic rat strains
      to determine the effects of C6 on cardiac allograft survival across individual
      donor-recipient major histocompatibility complex (MHC) disparities. METHODS:
      Hearts from C6-deficient PVG.1A (RT1a) donors were transplanted heterotopically
      to fully MHC-incompatible C6-sufficient and C6-deficient PVG.1L (RT1(1))
      recipients, as well as from C6-deficient PVG.R8 (RT1.AaBu) donors to MHC class I
      incompatible C6-sufficient and C6-deficient PVG. 1U (RT1.AuBu) recipients.
      RESULTS: Hearts from PVG.1A (C6-) female donors were rejected acutely (7 to 9
      days; n = 5) by fully MHC disparate female PVG.1L (C6+) recipients, but they
      survived significantly longer in female PVG.1L (C6-) recipients (13 to >50 days;
      n = 6). Slightly better survival resulted in male PVG.1L (C6-) heart transplant
      recipients of male PVG.1A (C6-) hearts (19 to >50 days [n = 5] vs 6 to 9 days for
      C6+ male PVG.1L recipients [n = 10]). The C6 deficiency had an even greater
      effect in PVG.1U recipients of class I MHC disparate PVG.R8 hearts (>50 day
      survival in C6- PVG.1U recipients [n = 5] vs 6 to 7 days in C6+ recipients [n =
      8]). The cardiac allografts elicited similarly vigorous immunoglobulin M and G
      alloantibody responses in the C6- and C6+ recipients as measured by flow
      cytometry. At the time of acute rejection, the hearts in the C6+ recipients
      demonstrated extensive vascular endothelial destruction. In contrast, rejection
      of hearts by C6- recipients was characterized by endothelialitis, but there was
      little destruction of the endothelium and limited proliferation of smooth muscle
      cells in the intima. CONCLUSIONS: These results demonstrate that the terminal
      complement component C6 can contribute to the rejection of class I or complete
      MHC-incompatible hearts in rats that have been characterized as "high"
      alloantibody responders.

PMID- 9628566
TI  - Should endomyocardial biopsy be performed for detection of myocarditis? A
      decision analytic approach.
AB  - BACKGROUND: Performance of endomyocardial biopsy (EMB) to diagnose myocarditis in
      patients with dilated cardiomyopathy is controversial because of a lack of
      evidence favoring immunosuppressive therapy. In spite of advances in heart
      failure treatment, dilated cardiomyopathy carries a poor prognosis, and
      myocardial inflammation and viral infection are potential therapeutic targets.
      METHODS: We used decision analysis to determine the efficacy (5-year risk
      reduction in mortality or transplantation) that a treatment for myocarditis would
      require to favor a biopsy-guided approach over conventional therapy. Literature
      based estimates included prevalence of myocarditis among patients with dilated
      cardiomyopathy with or without borderline myocarditis (16% and 11%,
      respectively); probability of 5-year transplantation-free survival (55%);
      sensitivity (50% and 63%, respectively), specificity (95.4%), and mortality rate
      (0.4%) of EMB; side effects resulting in withdrawal of immunosuppressive
      treatment (4%); and a 6-month mortality rate for immunosuppressive treatment
      (0.1%). All estimates were varied to determine impact on model results
      (sensitivity analysis). RESULTS: A therapy that decreased the rate of death or
      transplantation by 12.7% and 7.1% for patients without or with borderline
      myocarditis, respectively, favored EMB. Sensitivity analysis indicated that
      therapeutic efficacy was influenced by myocarditis prevalence and biopsy-related
      death, but not by accuracy of biopsy or probability of immunosuppressive therapy
      side effects. Randomized trials powered to detect 7% and 25% reductions in death
      and transplantation would require 5790 and 380 end points, respectively.
      CONCLUSION: Decreasing the rate of death or transplantation by 7.1% offsets
      therapy side effects, EMB-related death, and inaccuracies in histologic
      diagnosis. Prospective randomized trials of treatments for myocarditis may be
      more feasible during periods of high prevalence or with more sensitive diagnostic
      techniques.

PMID- 9628567
TI  - Discordant epicardial and microvascular endothelial responses in heart transplant
      recipients early after transplantation.
AB  - BACKGROUND: Cardiac allograft vasculopathy represents the leading cause of death
      in heart transplant recipients who survive more than 1 year. Functional
      endothelial abnormalities are sensitive measures of the early development of
      cardiac allograft vasculopathy, but the relative importance of large and small
      coronary vessel abnormalities has not been evaluated. The purpose of the study
      was to distinguish between large and small coronary endothelial dysfunction in
      patients early after heart transplantation and to test the hypothesis that
      microvascular endothelial responses can be preserved in the presence of
      epicardial endothelial dysfunction. METHODS: Changes in epicardial lumen area and
      coronary artery blood flow in response to intracoronary administration of
      adenosine, acetylcholine, and nitroglycerin were measured simultaneously by use
      of an intravascular ultrasound catheter positioned over a Doppler flow wire in
      the left anterior descending coronary artery. The combination of these techniques
      allowed distinction between large and small coronary vascular responses. In 19
      patients studied early after transplantation, adenosine (16 and 32 microg),
      acetylcholine (5.4 and 54 microg), and nitroglycerin (200 microg) were infused,
      with continuous intravascular ultrasound imaging and Doppler velocity
      measurements. RESULTS: Acetylcholine induced paradoxical epicardial
      vasoconstriction in 12 of 19 patients (73% +/- 6% of baseline); vasodilation
      occurred in 7 (108% +/- 3%). In spite of this constriction, coronary artery flow
      increased in all 19 patients, to the same extent in patients with constriction
      and those with dilation (239 +/- 26 vs 193 +/- 20, p = 0.38). Adenosine and
      nitroglycerin increased area (107% +/- 1% and 112% +/- 3%) and flow (258% +/- 17%
      and 197% +/- 11%) in all patients. None of the area or flow responses correlated
      with the degree of intimal thickening. CONCLUSIONS: Acetylcholine increased
      coronary artery flow early after transplantation, indicating preserved
      microvascular responses in spite of epicardial vasoconstriction. Simultaneous
      measurement of area and velocity responses, by permitting evaluation of the
      relative contribution of epicardial and microvascular vessels, may offer unique
      insights into coronary endothelial function.

PMID- 9628568
TI  - Simultaneous evaluation of epicardial and microvascular function in human beings:
      a technical tour de force.

PMID- 9628569
TI  - Risk of death or incapacitation after heart transplantation, with particular
      reference to pilots.
AB  - Pilots who have received a heart transplant may subsequently want to resume
      flying. This study was undertaken to determine whether a group of heart
      transplant recipients who had a particularly low risk of sudden unexpected death
      could be identified from clinical data. An event, "rapid-onset death," was
      defined incorporating a number of possible causes of death that could result in a
      heart transplant recipient-pilot losing control of an airplane. The survival of
      3676 patients undergoing a first heart transplantation was 85% and 73% at 1 and 5
      years, respectively, the hazard function having a high early phase of risk. When
      time zero was moved to the beginning of the second year after transplantation,
      the freedom from "rapid-onset death" at posttransplantation year 2 and
      posttransplantation year 5 was 96.8% and 88%, respectively. For patients who had
      both a "normal" coronary angiogram and no episodes of acute heart rejection
      during the first year transplantation, the probability of "rapid onset death"
      during the second posttransplantation year was 1.4%, and given the same
      circumstances, during the third posttransplantation year the risk of "rapid-onset
      death" was 1.6%. This information is potentially useful to the Federal Aviation
      Administration for policy decisions regarding this issue.

PMID- 9628570
TI  - Application of solid-state pulsed-wave, mid-infrared laser for percutaneous
      revascularization in heart transplant recipients.
AB  - BACKGROUND: Severe allograft coronary artery disease is a significant cause of
      death in heart transplant recipients. Percutaneous revascularization has thus far
      been attempted with balloon angioplasty and, to a lesser extent, with directional
      atherectomy. The new, investigational, solid-state pulsed-wave mid-infrared laser
      (holmium:YAG) can vaporize and remove atheromatous and thrombotic plaques. This
      mechanism of plaque ablation may be useful for allograft coronary artery disease
      associated with focal stenoses deemed unsuitable for standard balloon
      angioplasty, especially thrombus-containing lesions. METHODS: Five adult heart
      transplant recipients with severe focal stenoses related to allograft coronary
      artery disease underwent six laser angioplasty procedures. Laser catheters (2.1
      microm, 250 to 600 mJ, 5 Hz) varying from 1.2 mm to 2.0 mm delivered 45 +/- 7.4
      pulses (mean +/- SD). Five laser procedures were completed with adjunct balloon
      angioplasty and one with directional atherectomy. RESULTS: Laser success (defined
      as stenosis reduction > 20%, no cardiac catheterization laboratory or in-hospital
      major complication) was achieved in six of seven lesions (85%), and the overall
      (laser and adjunct balloon) procedural success rate was 100%. No major
      complications occurred. Laser-assisted angioplasty reduced mean stenosis from 90%
      +/- 3% to 9% +/- 11%. All five patients recovered and were discharged.
      Angiographic follow-up demonstrated a 50% restenosis rate. CONCLUSIONS: In
      selected heart transplant recipients laser-assisted angioplasty can provide safe
      and successful acute revascularization. Focal lesions considered "nonideal" for
      balloon angioplasty and, in particular, thrombotic lesions can benefit from
      application of this device; however, long-term reduction of restenosis rates is
      not expected from this modality.

PMID- 9628571
TI  - Does lung transplantation prolong life? A comparison of survival with and without
      transplantation.
AB  - BACKGROUND: Because of the assumed beneficial effect of lung transplantation on
      survival, controlled trials to assess the therapeutic benefit of lung
      transplantation are considered to be unethical. Therefore other methods must be
      used to provide control data. In this study the effect of lung transplantation on
      survival for patients with end-stage pulmonary disease was analyzed, with waiting
      list survival rates used as control data. METHODS: The analysis was based on 157
      consecutive patients who were put on the waiting list of the Dutch lung
      transplantation program during the period November 1990 to January 31, 1996, of
      whom 76 underwent transplantation. Following the principles of control group
      estimation as set out in the context of heart transplantation, a stepwise
      approach was used to arrive at a multivariate time-dependent Cox regression
      model. The following prognostic variables were included in the analyses: age,
      forced expiratory volume in 1 second, partial pressure of carbon dioxide, partial
      pressure of oxygen, and diagnosis. RESULTS: The 1- and 2-year waiting list
      survival rates were 78% and 58%, respectively. The 1- and 2-year transplantation
      survival rates (i.e., survival from placement on the waiting list, including
      posttransplantation survival) were 79% and 64%, respectively. The multivariate
      time-dependent Cox analysis showed that lung transplantation reduced the risk of
      dying by 55% (95% confidence interval, 3% to 79%). For patients with emphysema
      the risk of dying was estimated to be 77% lower than for patients with other
      diagnoses (96% confidence interval, 50% to 89%). CONCLUSIONS: With Cox
      regression, adjusting for age, forced expiratory volume in 1 second, partial
      pressure of carbon dioxide, partial pressure of oxygen, and diagnosis, lung
      transplantation showed a statistically significant effect on survival in selected
      patients with end-stage pulmonary disease.

PMID- 9628572
TI  - Association between blood eosinophil counts and acute cardiac and pulmonary
      allograft rejection.
AB  - BACKGROUND: Peripheral blood eosinophilia is a particularly early and specific
      marker of both renal and hepatic allograft rejection. Therefore we evaluated the
      relationship between blood eosinophil counts and cardiac and pulmonary allograft
      rejection. METHODS: Differential blood counts were available within 3 days before
      383 endomyocardial biopsy specimens in 56 heart transplant recipients. Blood
      counts were also available before 84 treated rejection episodes and 28
      transbronchial biopsy specimens showing no rejection in 58 lung transplant
      recipients. RESULTS: Cardiac allograft rejection: There was a significant
      association between the mean maximum blood eosinophil count and treated acute
      rejection (p < 0.01) and a linear relationship between this eosinophil count and
      the histologic grade of rejection (p < 0.01). The first increase in eosinophils
      occurred at a median of 4 days before treated rejection. Pulmonary allograft
      rejection: The mean maximum blood eosinophil count was 0.14 x 10(9)/L (95%
      confidence interval = 0.10, 0.18) preceding treated rejection, and this was
      significantly greater than the mean maximum blood eosinophil count of 0.07 x
      10(9)/L (confidence interval = 0.05, 0.09) measured when there was no rejection
      or during infection (p = 0.01). The first increase in eosinophil occurred at a
      median of 5 days before treated rejection. There was no relationship between
      blood neutrophil counts and either cardiac or pulmonary allograft rejection.
      CONCLUSIONS: An increase in peripheral blood eosinophils but not neutrophils is a
      specific and early marker of clinically significant rejection of both cardiac and
      pulmonary allografts. Furthermore, the maximum blood eosinophil count measured in
      the 3 days before rejection is linearly related to the severity of cardiac
      allograft rejection.

PMID- 9628573
TI  - Pulmonary graft preservation: a worldwide survey of current clinical practice.
AB  - BACKGROUND: Flush perfusion of pulmonary grafts with cold modified EuroCollins
      solution supplemented by prostaglandin treatment was introduced clinically 10
      years ago. Primary graft failure remains a major cause of morbidity and death
      after lung transplantation. During the last decade, much experimental work has
      led to reports of alternative storage solutions, differing storage conditions,
      and pharmacologic interventions that improve pulmonary graft performance. It is
      unclear how these findings have influenced current clinical practice. METHODS: A
      worldwide survey of the 125 centers performing lung transplantation was conducted
      by questionnaire. RESULTS: One hundred twelve replies were received (90%). Most
      centers (n = 86) continue to use EuroCollins solution (77%), of whom 69% include
      prostaglandin therapy and 32% donor steroid treatment. University of Wisconsin
      solution (UW) is used by 15 centers (13.5%), of which 10 (67%) use prostaglandin
      and seven (47%) use donor steroids. Nine centers use Papworth solution and one
      uses donor core cooling. The volume of flush used varied widely, from 20 to 120
      ml/kg, with median volumes of 60, 60, and 30 ml/kg in centers using EuroCollins,
      UW, and Papworth solutions, respectively. Two thirds of centers using EuroCollins
      solution store grafts at 0 degrees to 5 degrees C, and one third at 5 degrees to
      10 degrees C. One center that uses EuroCollins solution stores grafts at 10
      degrees to 15 degrees C. Centers using UW solution are evenly split at 0 degrees
      to 5 degrees C and 5 degrees to 10 degrees C. Most centers that use Papworth
      solution store grafts at 5 degrees to 10 degrees C. Only six centers use
      superoxide radical scavengers. The maximum ischemic period accepted by centers
      varies from 4 to 12 hours, with median periods of 8, 7, 6, and 6 hours for the
      UW, EuroCollins, Papworth, and donor core cooling centers, respectively. All but
      one of the UW centers (93%) expressed satisfaction with the quality of graft
      preservation achieved by UW solution. Only 58 of the 86 centers using EuroCollins
      solution (67%) were satisfied. Six of nine centers using Papworth solution were
      satisfied. CONCLUSIONS: There has been a trend toward the use of UW solution and
      a slightly warmer storage temperature. However, for most centers, graft storage
      techniques have changed little over the last decade.

PMID- 9628574
TI  - Studies in a modified auxiliary abdominal rat heart transplantation model:
      preservation with colloid-free University of Wisconsin solution.
AB  - BACKGROUND: Current clinical heart preservation is still limited to 6 hours. A
      suitable heart transplantation model to rapidly screen the effectiveness of new
      solutions is essential. This study examines a new screening test-a modification
      of the conventional abdominal rat heart transplantation model that overcomes its
      serious limitation of lack of quantitative evaluation of function. METHODS: Rat
      hearts, with an externalized intraventricular balloon-tipped catheter, were
      transplanted immediately (controls) or flushed and stored in colloid-free
      University of Wisconsin solution in ice for 6, 9, or 12 hours before
      transplantation. One and 7 days later this catheter was connected to a pressure
      transducer and a calibrated syringe. Heart rate, maximum developed pressure, and
      maximum rate of left ventricular pressure rise were determined. Grafts were
      prepared for histologic study on day 7. RESULTS: All preserved hearts commenced
      beating within 2 minutes (controls beat within 20 seconds). On day 1 the heart
      rate and chamber stiffness (deltaP/deltat) were similar in all groups. The 9- and
      12-hour-preserved hearts had significantly (p < 0.05) diminished developed
      pressure and contractility. On day 7 contractility and developed pressure
      improved in 9- and 12-hour-preserved grafts. There was extensive muscular atrophy
      and necrosis, with extensive cellular infiltrate in the 9- and 12-hour-preserved
      grafts; other grafts showed no damage. CONCLUSION: This quantitative model
      provides an ischemia-related gradation of function and greater discrimination
      than conventional methods. It has refuted previous studies suggesting effective
      preservation for 20 hours and demonstrated that functional testing is essential
      in evaluating preservation regimens.

PMID- 9628575
TI  - Increased production of beta2-microglobulin after heart transplantation.
AB  - Serum beta2-microglobulin (beta2m) levels were measured to evaluate the state of
      immunoactivation in stable heart transplant recipients. Serum beta2m and renal
      function of 29 heart transplant recipients were compared with 16 control
      subjects, who were age and sex matched, and 11 patients with chronic kidney
      failure. Serum creatinine and 24-hour urine collection for albuminuria were used
      as markers of renal impairment. Heart transplant recipients with normal renal
      function (n = 7) had significantly elevated beta2m levels compared with control
      subjects: 2.6 +/- 0.9 vs 1.66 +/- 0.32 microg/ml, p < or = 0.05. Heart transplant
      recipients with impaired renal function (n = 22) had significantly elevated
      beta2m compared with the chronic kidney failure group: 4.42 +/- 1.3 vs 3.49 +/-
      0.66 microg/ml (p < or = 0.05); although there was no significant difference in
      serum creatinine levels. Albuminuria excretion was significantly elevated in the
      chronic kidney failure group compared with the heart transplant recipients with
      impaired renal function (p < or = 0.05). Elevated serum beta2m in heart
      transplant recipients suggests increased beta2m production, reflecting increased
      immunoactivation. This observation could be useful in monitoring long-term
      immunosuppressive therapy.

PMID- 9628576
TI  - Complete nucleotide sequences of 93-kb and 3.3-kb plasmids of an
      enterohemorrhagic Escherichia coli O157:H7 derived from Sakai outbreak.
AB  - Enterohemorrhagic Escherichia coli (EHEC) O157:H7, derived from an outbreak in
      Sakai city, Japan in 1996, possesses two kinds of plasmids: a 93-kb plasmid
      termed pO157, found in clinical EHEC isolates world-wide and a 3.3-kb plasmid
      termed pOSAK1, prevalent in EHEC strains isolated in Japan. Complete nucleotide
      sequences of both plasmids have been determined, and the putative functions of
      the encoded proteins and the cis-acting DNA sequences have been analyzed. pO157
      shares strikingly similar genes and DNA sequences with F-factor and the
      transmissible drug-resistant plasmid R100 for DNA replication, copy number
      control, plasmid segregation, conjugative functions and stable maintenance in the
      host, although it is defective in DNA transfer by conjugation due to the
      truncation and deletion of the required genes and DNA sequences. In addition, it
      encodes several proteins implicated in EHEC pathogenicity such as an EHEC
      hemolysin (HlyA), a catalase-peroxidase (KatP), a serine protease (EspP) and type
      II secretion system. pOSAK1 possesses a ColE1-like replication system, and the
      DNA sequence is extremely similar to that of a drug-resistant plasmid, NTP16,
      derived from Salmonella typhimurium except that it lacks drug resistance
      transposons.

PMID- 9628577
TI  - Identification of the region required for monomerization of the rolling circle
      plasmid pKYM.
AB  - Plasmid pKYM, isolated from the gram-negative bacterium Shigella sonnei, is a
      small multicopy plasmid which replicates by a rolling circle mechanism. The
      formation of multimers has been observed in a derivative of pKYM which lost a
      part of the origin region, and the loss of the monomerization mechanism would
      have led to these multimers. By analyzing the constructs of several mutants, we
      discovered that a DNA region required for monomerization was present upstream of
      the RepK binding site in the replication origin. As either of the T-rich sequence
      or the inverted repeat sequences which were seen in that region have been lost in
      the multimer-forming plasmids, these sequences may be necessary for
      monomerization.

PMID- 9628578
TI  - Mapping of rice Rf gene by bulked line analysis.
AB  - A method, bulked line analysis (BLA), was developed for identification of the
      RFLP markers associated with a target gene. Instead of segregating progenies,
      conventional lines sharing the same trait were bulked by the BLA method. This
      method is an alternative approach to the identification of DNA markers linked
      with a target gene. A major advantage of this method is time-saving for genetic
      stock development. The advantage is very significant for organisms having a long
      generation period. This method has been tested by using fertility restoration of
      rice cytoplasmic male sterility of wild abortive type as a target trait. A
      fertility-restoring gene was successfully identified by linkage with RFLP
      markers. This gene was mapped in the middle of the long arm of chromosome 10 of
      the rice genome.

PMID- 9628579
TI  - Contig map of the Parkinson's disease region on 4q21-q23.
AB  - We have constructed a yeast artificial chromosome contig (YAC) map of human
      chromosome 4q21-q23 across the Parkinson's disease region by combining molecular
      and fluorescence in situ hybridization techniques. This map contains 55 YACs and
      51 molecular markers, including 23 polymorphic markers. We have also isolated one
      P1 and 33 bacterial artificial chromosomes located within this contig. Plasmid
      libraries were generated from 11 of these BAC and P1 clones, and 614 random
      plasmid clones were sequenced for a total of about 200 kb. This contig allowed us
      to precisely determine the location of 18 transcripts within the D4S2460-D4S2986
      interval, including the alpha-synuclein gene found to be mutated in some families
      with Parkinson's disease.

PMID- 9628580
TI  - A novel superoxide dismutase gene encoding membrane-bound and extracellular
      isoforms by alternative splicing in Caenorhabditis elegans.
AB  - We have identified a novel Cu/Zn superoxide dismutase gene (termed SOD-4) in
      Caenorhabditis elegans. Characterization of its complementary DNA revealed that
      the gene encodes two isoforms by alternative splicing, SOD4-1 and SOD4-2 which
      differ in their C-terminal exons. Their predicted amino acid sequences include a
      consensus signal peptide at their N-termini and are homologous to the
      extracellular-types of Cu/Zn superoxide dismutase in mammals. In addition, SOD4-2
      possesses a putative transmembrane domain at the C-terminal region. When
      transiently expressed in Chinese hamster ovary cells, both types were found in
      the membranes and SOD4-1 also in the culture fluid. It is, therefore, indicated
      that SOD4-1 is an extracellular form and SOD4-2 a membrane-bound form, the latter
      representing a novel type of SOD. In C. elegans, SOD4-2 mRNA was found to be
      preferentially expressed in eggs.

PMID- 9628581
TI  - Prediction of the coding sequences of unidentified human genes. IX. The complete
      sequences of 100 new cDNA clones from brain which can code for large proteins in
      vitro.
AB  - As an extension of a series of projects for sequencing human cDNA clones derived
      from relatively long transcripts, we herein report the entire sequences of 100
      newly determined cDNA clones with the potential of coding for large proteins in
      vitro. The cDNA clones were isolated from size-fractionated human brain cDNA
      libraries with insert sizes between 4.5 and 8.3 kb. The sequencing of these
      clones revealed that the average size of the cDNA inserts and of their open
      reading frames was 5.3 kb and 2.8 kb (930 amino acid residues), respectively.
      Homology search against public databases indicated that the predicted coding
      sequences of 86 clones exhibited significant similarities to known genes; 51 of
      them (59%) were related to those for cell signaling/communication, nucleic acid
      management, and cell structure/motility. All the clones characterized in this
      study are accompanied by their expression profiles in 14 human tissues examined
      by reverse transcription-coupled polymerase chain reaction and the chromosomal
      mapping data.

PMID- 9628582
TI  - Structural analysis of Arabidopsis thaliana chromosome 5. IV. Sequence features
      of the regions of 1,456,315 bp covered by nineteen physically assigned P1 and TAC
      clones.
AB  - Nineteen P1 and TAC clones, which have been precisely localized to the fine
      physical map of Arabidopsis thaliana chromosome 5, were newly sequenced, and
      their sequence features were analysed. The total length of the clones sequenced
      was 1,456,315 bp. Together with the previously reported sequences, the regions of
      chromosome 5 that have been sequenced to date is now 5,310,105 bp. When the
      sequences determined in this study were subjected to similarity search against
      protein and expressed sequence tag (EST) databases and analysis with computer
      programs for gene modeling, a total of 354 potential protein-coding genes and/or
      gene segments were identified. The average density of the assigned genes and/or
      gene segments was one gene per 4,114 bp. Introns were identified in 75% of the
      potential protein genes, and the average number per gene and the average length
      of the introns were 3.7 and 194 bp, respectively. These sequence features are
      essentially identical to those in the previously reported sequences. The numbers
      of the Arabidopsis ESTs matched to each of the predicted genes have been counted
      to monitor the transcription level. The sequence data and gene information are
      available on the World Wide Web database KAOS (the Kazusa Arabidopsis data
      Opening Site) at http://www.kazusa.or.jp/arabi/.

PMID- 9628583
TI  - Induction of p53 without increase in p21WAF1 in betulinic acid-mediated cell
      death is preferential for human metastatic melanoma.
AB  - Because betulinic acid was recently described as a melanoma-specific inducer of
      apoptosis, we investigated whether this agent was comparably effective against
      metastatic tumors and those in which metastatic ability and 92-kD gelatinase
      activity had been decreased by introduction of a normal chromosome 6. Human
      metastatic C8161 melanoma cells showed greater DNA fragmentation and growth
      arrest and earlier loss of viability in response to betulinic acid than their non
      metastatic C8161/neo 6.3 counterpart. These effects involved induction of p53
      without activation of p21WAF1 and were synergized by bromodeoxyuridine in
      metastatic Mel Juso, with no comparable responses in non-metastatic Mel Juso/neo
      6 cells. Our data suggest that betulinic acid exerts its inhibitory effect partly
      by increasing p53 without a comparable effect on p21WAF1.

PMID- 9628584
TI  - Genomic structure and sequence analysis of human HOXA-9.
AB  - In order to understand the regulatory mechanisms establishing and maintaining
      HOXA-9 gene expression, structural information about the gene is a prerequisite.
      Therefore, we sequenced the 7.2-kb region of the human HOXA-9 gene and mapped the
      positions of two partial cDNAs consisting of one of two 5' exons, AB (358 bp) or
      CD (568 bp), and a common 3' exon (exon II), which are separated by 5.4- and 1.0
      kb introns, respectively. When the amino acid sequence homologies were compared
      with those of other Hox genes belonging to the same paralogous group, exon CD
      exhibited the strongest homology: 73% of 91 aa residues exactly matched those of
      chicken Hoxa-9. An intermediate exon (90 bp) was detected within exon CD. It was
      surrounded by a splice acceptor and a donor at both the 5' and 3' ends, and one
      branchpoint site was found near the splice-acceptor site. Nucleotide sequence
      analysis along this region revealed two TATA boxes, one CAAT box, one GC box, and
      one each of the following binding sites--engrailed, eve-stripe2-hb3, and Krox20-
      just upstream of exon CD. A CpG island and two RARE repeats were detected within
      intron I. Northern blot analysis showed that at least four main transcripts were
      generated along this region: all fetal tissues tested (brain, lung, liver, and
      kidney) produced a 1.8-kb homeobox-containing transcript (HA-9A); a 2.2- and a
      3.3-kb transcript were generated from exon CD and exon II (HA-9B), especially in
      fetal and adult kidneys as well as in adult skeletal muscle; the 1.0-kb
      transcript was likely to be generated by the intermediate exon in all adult and
      fetal tissues. Several weak bands without tissue specificity were likely to be
      contributed by the hybrid transcripts between HOXA-9 and the other HOXA gene(s).
      Together, these results may account for the unique degree of conservation of the
      HOX cluster in general.

PMID- 9628585
TI  - Characterization of hepatitis B virus integrant that results in chromosomal
      rearrangement.
AB  - A hepatitis B virus (HBV) integrant was cloned from the genomic DNA library of
      human hepatocellular carcinoma cell line, Hep3B. Sequence analysis of the
      restriction fragment bearing the virus-host junction revealed that its
      integration pattern was the common type, with the right junction located at the
      cohesive region. The open reading frame of the major viral surface antigen was
      intact with rearranged preS1 and core sequences. The X protein, although
      truncated, maintained the trans-activating activity to simian virus 40
      enhancer/promoter. S1 nuclease mapping showed that 4.0-, 2.9-, and 2.2-kb HBV
      RNAs detected in Hep3B cells were transcribed from this integrant using preS2/S
      promoter. By somatic-cell hybrid mapping, the left and right cellular flanking
      sequences were assigned to chromosomes 13 and 4, respectively. The results of
      this study support the notion that integrated hepatitis B virus, resulting in
      chromosomal rearrangement as well as the production of the carboxy-terminal
      truncated X protein with trans-activating activity, is important for viral
      hepatocarcinogenesis.

PMID- 9628586
TI  - Control of expression and methylation of a hepatitis B virus transgene by strain
      specific modifiers.
AB  - In transgenic animals, genotype-specific modifiers exert a control over transgene
      methylation and expression that may or may not be position dependent. These
      factors belong to different classes, some of them possibly related to modifiers
      of position-effect variegation in Drosophila. The study of hepatitis B virus
      (HBV) gene expression in transgenic mice has revealed the existence of many
      factors influencing transcription, including hormones and tissue-specific
      transcription factors. We now report the effect of genotype-specific modifiers on
      HBV surface antigen (HBsAg) expression and transgene methylation. Compared with
      the C57BL/6 background, the DBA/2 and 129sv backgrounds cause enhancement of
      HBsAg expression, with little or not effect on transgene methylation or
      transcription. In contrast, a single cross with a BALB/c mouse is responsible for
      de novo methylation and silencing of the transgene in all offspring. Several
      modifiers appear to segregate in the progeny of a transgenic E36 male mouse
      crossed with (C57BL/6 x BALB/c) F1 females, with the emergence of a high
      expressor group. Our observations suggest that different modifiers act
      cooperatively, at both the transcriptional and post-transcriptional levels, as
      part of a complex system regulating transgene expression. This transgenic model
      provides a system to genetically map new mouse strain-specific modifiers, some of
      them involved in epigenetic modification and transcription control.

PMID- 9628587
TI  - drp, a novel protein expressed at high cell density but not during growth arrest.
AB  - Contact is a vital mechanism used by cells to interact with their environment.
      Contact with living and nonliving elements adjacent to a cell is the basis for
      many common biological events ranging from growth regulation to metastasis to
      embryonic pattern formation. We describe the cloning and characterization of a
      novel density-regulated protein (drp) whose expression is increased in cultured
      cells at high density compared with cells at low density. A drp cDNA was isolated
      from the human teratocarcinoma cell line PA-1. Northern analysis with a drp probe
      revealed transcripts of 2.8 and 3.2 kb. The drp RNA was expressed in a variety of
      tissues, with the highest amounts in skeletal and cardiac muscle. Using
      antipeptide antisera, increasing amounts of a 70-kDa protein were detected using
      several experimental approaches in several cells lines as cell density is
      increased. Conditioned medium from high-density cells was unable to induce
      expression of drp in cells growing at low density. Similarly, growth arrest by
      serum starvation or transforming growth factor-beta (TGF-beta) treatment failed
      to elicit drp expression. We conclude that drp is a novel protein whose
      expression is increased at high cell density but not growth arrest.

PMID- 9628588
TI  - Identification of multiple forms of 180-kDa ribosome receptor in human cells.
AB  - Herein, we describe the analysis and mapping of cDNA clones encoding variant
      forms of the human homolog of the canine 180-kDa ribosome receptor (p180). One
      form, similar to the chicken ES/130 homolog, possesses a large uninterrupted C
      terminal region composed predominantly of heptad repeats predicted to form an
      alpha-helical double-stranded coiled-coil rod. Other forms contain in addition a
      10-amino acid consensus motif, NQGKKAEGAQ, repeated up to 54 times in tandem
      close to the N-terminus. Such repeats in canine p180 represent a ribosome-binding
      domain. The cDNA hybridized to a major 6-kb transcript in all tissues examined,
      where very high expression was observed in tissues that carry out a high level of
      secretion such as pancreas, liver, and placenta. The ES130/p180 gene was mapped
      to chromosome 20p12, and a potential pseudogene appears to reside on chromosome
      7. In summary, the data suggest that p180 exists in humans in different forms
      because of complete removal of tandem repeats, or partial intraexonic splicing,
      creating different repeat lengths with potentially novel ribosome-binding
      characteristics.

PMID- 9628589
TI  - Nuclear factor-1 motif and redundant regulatory elements comprise phenobarbital
      responsive enhancer in CYP2B1/2.
AB  - Although the induction of drug-metabolizing systems by phenobarbital has been
      recognized for about 40 years, the mechanism by which cytochrome P450 gene
      expression is increased is still not well understood. A 163-bp fragment at about 
      2.2 Kb in CYP2B2 has been shown to mediate phenobarbital induction in primary rat
      hepatocytes (Trottier, et al. [1995] Gene 158:263-268) and by an in situ
      transient transfection assay in rat liver (Park, Y., et al. [1996]. J. Biol.
      Chem. 271:23725-23728). Deletion mutations of this fragment indicated that the 88
      bp stretch from -2258 to -2170 was the minimal sequence that could mediate
      phenobarbital induction in the in situ system if single copies of the deleted
      fragments fused to the CYP2C1 proximal promoter were assayed. If three copies of
      the fragments were present, 5' and 3' deletions defined a minimal 37-bp core
      fragment, which, although necessary for phenobarbital responsiveness, was not
      sufficient unless additional sequence was present at either end, suggesting that
      redundant elements were present in the two flanking regions. Site-specific
      mutagenesis of an NF-1 site within the 88-bp fragment and linker scanning
      mutagenesis across the fragment indicated that the NF-1 site and a region to the
      5' side of the site contributed to the magnitude of the response, but neither the
      NF-1 mutations nor any of the linker scanning mutations eliminated the response
      to phenobarbital. Mutation in a region 3' of the NF-1 site resulted in elevated
      basal expression without substantial effects on phenobarbital-induced expression.
      Binding of NF-1 to the 37-bp core fragment was established by gel-shift
      competition studies and by supershifts of the protein-DNA complexes by antisera
      to NF-1. Additional protein-DNA complexes were detected in the regions flanking
      the NF-1 site. These studies indicate that the CYP2B2 phenobarbital-responsive
      enhancer contains multiple constitutive and phenobarbital-responsive elements.
      Binding of nuclear proteins from control or phenobarbital-treated animals in
      vitro to this region was very similar. The only difference detected was a complex
      that was substantially reduced by phenobarbital treatment and mapped to the 3'
      side of the NF-1 site.

PMID- 9628590
TI  - Sp family transcription factors regulate expression of rat D2 dopamine receptor
      gene.
AB  - The rat D2 dopamine receptor gene is transcribed from a TATA-less promoter that
      has an initiator-like sequence and several putative Sp1 binding sites. We
      previously reported that a negative modulator is located between nucleotides -116
      and -76 (D2Neg-B) in this gene and that Sp1 as well as another unknown factor
      bind to this region (Minowa et al., J. Biol. Chem. 269, 11656, 1994). In the
      present investigation employing the in situ filter detection method, we
      identified this factor as Sp3. Anti-Sp3 antiserum used in gel-shift assays also
      revealed that Sp3 binds to the D2Neg-B sequence. Cotransfection of Drosophila
      Schneider's SL2 cells with Sp3 or Sp1 expression plasmids in the presence of CAT
      reporter plasmids containing D2 promoter regions demonstrated that Sp1 increased
      CAT activity in a dose-dependent manner, whereas Sp3, either alone or in the
      presence of Sp1, failed to activate or repress transcription. On the other hand,
      using the TATA-containing reporter plasmid BCAT-2, Sp3 coexpression significantly
      repressed Sp1-induced trans-activation, although Sp3 alone was ineffective. Thus,
      the transcriptional activity of Sp3 is dependent on the promoter context, and the
      negative regulation of D2 gene expression appears quite complex and may not
      depend simply on known DNA-protein interactions involving only Sp1 and Sp3.

PMID- 9628591
TI  - Regulation of CCSP (PCB-BP/uteroglobin) expression in primary cultures of lung
      cells: involvement of C/EBP.
AB  - The Clara-cell secretory protein (CCSP) is a cell-specific differentiation marker
      for the bronchiolar Clara cell. Isolated rat Clara and alveolar type 2 cells kept
      in primary culture proliferate and dedifferentiate, providing the opportunity to
      study differentiation-dependent mechanisms. In freshly isolated Clara cells, high
      levels of CCSP and the corresponding mRNA were detected. During culture in vitro,
      these levels decreased. In the type 2 cell fraction, low levels of CCSP were
      detected, which decreased further during culture. A promoter fragment of the rat
      CCSP gene encompassing the sequence from -188 to +53 was able to drive high-level
      expression of reporter genes in transfected Clara cells. Reporter gene expression
      in transfected type 2 cells was markedly lower, and no expression could be
      detected in alveolar macrophages. Expression of transcription factors previously
      described to stimulate CCSP expression appeared not to parallel CCSP levels in
      the primary Clara cells. However, expression of the transcription factor C/EBP
      alpha correlated with the CCSP expression pattern. In electrophoretic mobility
      shift assays, we were able to demonstrate binding of C/EBP alpha from rat Clara
      cell nuclear extracts to an element located 85 bp upstream of the start site of
      transcription. Overexpression of C/EBP alpha increased expression from the CCSP 
      188 promoter fragment up to fivefold in NCI-H441-cells and 30-fold in A549-cells,
      establishing the functional importance of C/EBP alpha. Our results show that
      primary cultures of Clara cells constitute a useful model for investigating
      terminal airway differentiation and suggest a role for C/EBP-factor(s) in this
      process.

PMID- 9628592
TI  - Innovative therapies for human prostate cancer.

PMID- 9628593
TI  - Encrusted cystitis and pyelitis.
AB  - PURPOSE: Encrusted cystitis and pyelitis are chronic inflammations of the bladder
      and collecting system associated with mucosal encrustations induced by urea
      splitting bacteria. We review these infectious diseases. MATERIALS AND METHODS: A
      literature search was performed of the MEDLINE database from 1985 to 1997.
      Additional articles published before 1985 were also selectively included.
      RESULTS: Most of the articles were case reports or short series. During the last
      10 years increasing numbers of cases have been diagnosed, especially in
      immunodepressed patients, and particularly in renal transplant recipients. Many
      bacteria have been demonstrated in this infection but Corynebacterium group D2 is
      currently the most frequent. The development of encrusted cystitis or pyelitis
      requires the presence of specific bacteria with an alkaline urine, a preexisting
      urological procedure and a clinical context predisposing to infection. Clinical
      diagnosis can be difficult but the presence of alkaline urine containing abundant
      calcified mucopurulent debris is highly suggestive. Demonstration of the bacteria
      requires prolonged cultures in enriched media. Treatment is based on adapted
      antibiotic therapy, acidification of urine and excision of plaques of calcified
      encrustation. The consequences of treatment failure are serious and can result in
      graft nephrectomy in kidney transplant recipients. CONCLUSIONS: Early clinical
      and bacterial diagnosis of encrusted cystitis and pyelitis could improve the
      prognosis of these infectious diseases.

PMID- 9628594
TI  - The journal's journey.

PMID- 9628596
TI  - Laparoscopic nephrectomy: the experience of the laparoscopy working group of the
      German Urologic Association.
AB  - PURPOSE: The centers of the laparoscopy working group of the German Urologic
      Association collected data to prove the efficacy, safety and reproducibility of
      laparoscopic nephrectomy. MATERIALS AND METHODS: At 14 centers 482 laparoscopic
      nephrectomies have been performed until December 1996 via a transperitoneal
      approach in 344 (71%) and a retroperitoneal approach in 138 (29%). All 482
      laparoscopic nephrectomies were performed by a total of 20 surgeons with an
      average of 24 procedures per surgeon (range 4 to 105). The indications for
      nephrectomy were benign renal pathology in 444 patients (92%), including
      renovascular disease in 28%, hydronephrosis in 20%, reflux nephropathy in 15%,
      chronic pyelonephritis in 12%, end stage nephrolithiasis in 11%, renal dysplasia
      in 4% and renal tuberculosis in 1%. Of the remaining 38 patients (8%)
      laparoscopic radical nephrectomy was performed for renal cell carcinoma in 5% and
      for upper tract transitional cell carcinoma in 3%. RESULTS: Operating time
      depended mainly on the pathology of the kidney (that is small dysplastic organ
      versus large hydronephrosis) and the learning curve of the surgeon. However, the
      average operating time did not vary significantly among the different centers
      (maximum 277.6 and minimum 81.9 minutes). Intraoperative or perioperative
      complications were noted in 29 patients (6.0%), including bleeding in 22 (4.6%),
      bowel injury in 3, hypercarbia in 2 and pleura lesion in 1 and pulmonary embolism
      in 1. The conversion rate was 10.3% (bleeding, bowel injury, difficult
      dissection), including 4 patients with renal tuberculosis, 2 with
      xanthogranulomatous nephritis, and 1 each following renal trauma and
      embolization. The re-intervention rate was 3.4% due to bleeding in 6 cases,
      abscess formation in 3, intestinal stenosis in 2 and a pancreatic fistula and
      port hernia in 1. Mean hospital stay was 5.4 days. CONCLUSIONS: Laparoscopic
      nephrectomy has become a well established procedure in those urology departments
      focusing on laparoscopy. The indications and results are reproducible at these
      centers. However, for patients with severe perinephritis (that is renal
      tuberculosis, xanthogranulomatous nephritis, posttraumatic atrophy) a higher
      likelihood of open conversion must be considered.

PMID- 9628595
TI  - 5-year outcome of surgical resection and watchful waiting for men with moderately
      symptomatic benign prostatic hyperplasia: a Department of Veterans Affairs
      cooperative study.
AB  - PURPOSE: We determine outcomes after 5 years of followup for men who were
      randomized to receive transurethral resection or watchful waiting for moderate
      symptoms of benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 556
      patients were evaluated up to 60 months after randomization providing 966 patient
      years of followup for transurethral prostatic resection and 990 for watchful
      waiting. Patients randomized to watchful waiting were evaluated according to
      whether they remained on treatment or crossed over to surgery. Outcomes included
      treatment failure, a genitourinary symptom score, peak flow rate, post-void
      residual urine volume and the degree of bother from genitourinary symptoms.
      RESULTS: All outcomes were significantly better for transurethral prostatic
      resection than for watchful waiting. Treatment failure rates were 10% for
      transurethral prostatic resection versus 21% for watchful waiting (p = 0.0004).
      The crossover rate at 5 years was 36% and was positively associated with the
      degree of bother. Men with low pretreatment peak flow rates who were randomized
      to transurethral prostatic resection had 85% greater improvement in peak flow
      rate than comparable men who were randomized to watchful waiting and eventually
      crossed over to resection. However, after crossover, bother from genitourinary
      symptoms was similar to that of the resection group. CONCLUSIONS: For men with
      moderate symptoms of benign prostatic hyperplasia transurethral prostatic
      resection has more favorable outcomes up to 5 years of followup compared to
      watchful waiting. While many men do well on watchful waiting, those who undergo
      transurethral prostatic resection after a trial of watchful waiting have less
      improvement in measures of bladder function than men randomized to resection,
      although there is no difference in serious adverse outcomes or bother from
      genitourinary symptoms.

PMID- 9628597
TI  - Hand assisted laparoscopic nephrectomy: comparison to standard laparoscopic
      nephrectomy.
AB  - PURPOSE: We report our initial experience with hand assisted laparoscopic
      nephrectomy, and compare it to our results of standard laparoscopic nephrectomy.
      MATERIALS AND METHODS: The results of 21 hand assisted and standard laparoscopic
      nephrectomies (15 simple and 4 radical nephrectomies, and 2 nephroureterectomies)
      were reviewed. Hand assisted laparoscopic nephrectomy was performed with a hand
      placed intra-abdominally using the Pneumo Sleeve,* in addition to standard
      laparoscopic instruments manipulated through laparoscopic ports. Standard
      laparoscopic nephrectomy was performed using laparoscopic instruments alone.
      Perioperative data were recorded and questionnaires, including visual analog pain
      scales, were administered prospectively to 17 of 21 cases. RESULTS: The average
      operative time for 13 hand assisted laparoscopic nephrectomies was 240 minutes,
      which was significantly less than the 325-minute average for 8 standard
      laparoscopic nephrectomies (p = 0.04). Major complications tended to be more
      frequent in the standard group (38 versus 8%, p = 0.10). Hospital stay, return to
      normal activity and corrected 2-week abdominal/flank pain score in the hand
      assisted group (3.1 days, 14 days and 0.8, respectively) were not significantly
      different from the standard group (3.0 days, 10 days and 0.2, respectively).
      CONCLUSIONS: Compared to standard laparoscopic techniques, hand assistance
      appears to facilitate the operative speed and safety of laparoscopic nephrectomy
      without sacrificing the benefits of minimally invasive surgery. Hand assistance
      may make laparoscopic nephrectomy more appealing to urologists without advanced
      laparoscopic experience, may facilitate the laparoscopic management of demanding
      pathological conditions and is particularly useful when intact specimens are
      required. Hand assistance, by improving manipulative ability and tactile sense,
      is helpful for select cases of laparoscopic nephrectomy.

PMID- 9628598
TI  - Urological laparoscopy--why bother?

PMID- 9628599
TI  - Salvage radical cystoprostatectomy and orthotopic urinary diversion following
      radiation failure.
AB  - PURPOSE: Salvage surgery followed by lower urinary tract reconstruction is a
      viable therapeutic option for patients in whom definitive radiation therapy for
      localized bladder or prostate cancer has failed. Improvements in surgical
      technique and postoperative care have significantly improved overall outcome. An
      enhanced understanding of the rhabdoid sphincteric mechanism responsible for
      maintaining urinary continence following cystoprostatectomy has helped make the
      orthotopic neobladder the procedure of choice for patients requiring lower
      urinary tract reconstruction. We describe our experience with salvage surgery and
      orthotopic bladder substitution following failed radical radiation therapy.
      MATERIALS AND METHODS: We evaluated the complications of 18 patients in whom
      definitive radiation therapy (total minimum dose 60 Gy. or greater) for bladder
      or prostate cancer had failed. All patients underwent a salvage procedure with
      creation of an orthotopic neobladder. RESULTS: Operative characteristics,
      postoperative outcomes and postoperative complications related or unrelated to
      urinary reconstruction were similar between irradiated and nonirradiated
      patients. Good day and night continence following surgery was reported by 67 and
      56% of irradiated patients, respectively. Patients with poor postoperative
      continence were successfully treated with the placement of an artificial urinary
      sphincter. CONCLUSIONS: Salvage surgery with orthotopic urinary reconstruction is
      a safe, effective procedure that provides a functional lower urinary tract in
      patients in whom definitive pelvic radiation therapy has failed.

PMID- 9628600
TI  - The incidence of a positive ice water test in bladder outlet obstructed patients:
      evidence for bladder neural plasticity.
AB  - PURPOSE: The ice water test triggers a C fiber, capsaicin sensitive spinal
      micturition reflex. We postulated that the ice water test is positive in a high
      proportion of patients with compared to those without bladder outlet obstruction.
      MATERIALS AND METHODS: Prospective evaluation of 111 consecutive patients was
      undertaken. Symptoms of urgency, urge incontinence, nocturia and daytime
      frequency as well as the presence of neurological disease were obtained from
      history and physical examination. Fluorourodynamics, including ice water
      cystometry, and pressure-flow studies were done for all 111 subjects. Obstruction
      was defined using the Abrams-Griffith nomogram and urethral resistive index. A
      positive ice water test was defined as presence of uninhibited bladder
      contraction with instillation of 0C saline at 50 cc per minute up to a maximum of
      250 cc. Detrusor instability was defined according to the International
      Continence Society criteria using room temperature saline instillation. RESULTS:
      When patients with neurological disease were excluded, a positive ice water test
      was found in 71% of subjects with bladder outlet obstruction (12 of 17), which
      was significantly higher (p <0.0005, Yates corrected chi-square test) than the 7%
      positive ice water test rate in nonobstructed subjects (3 of 44). Conversely, the
      incidence of positive detrusor instability was not statistically different
      between the patients with or without bladder outlet obstruction. Of the subjects
      with neurological disease 85% (42 of 50) had a positive ice water test. The
      incidence of a positive ice water test was only 5 to 9% in patients with storage
      lower urinary tract symptoms. CONCLUSIONS: A positive ice water test has been
      previously described in infants and individuals with neurogenic bladders.
      However, subjects with bladder outlet obstruction had a significantly higher
      incidence of a positive ice water test compared to those without it, supporting
      the hypothesis of an enhanced spinal micturition reflex possibly due to
      plasticity of bladder afferents after bladder outlet obstruction. The ice water
      test may be useful in prognosticating bladder outlet obstruction treatment
      outcomes and determining the etiology of treatment failure.

PMID- 9628601
TI  - Photodynamic therapy using porfimer sodium as an alternative to cystectomy in
      patients with refractory transitional cell carcinoma in situ of the bladder.
      Bladder Photofrin Study Group.
AB  - PURPOSE: Photodynamic therapy combines a photosensitizer, such as porfimer sodium
      (Photofrin), with red laser light (630 nm.) to destroy cancer cells.
      Investigators have reported the effectiveness of photodynamic therapy in the
      treatment of patients with recurrent superficial bladder cancer. We assess the
      safety and efficacy of 1 or 2 photodynamic treatments using porfimer sodium and
      controlled uniform laser light (630 nm.) as an alternative to cystectomy in
      patients with refractory vesical carcinoma in situ of the bladder. MATERIALS AND
      METHODS: A total of 36 patients with carcinoma in situ were treated with whole
      bladder photodynamic therapy as an alternative to cystectomy. In all patients at
      least 1 course of bacillus Calmette-Guerin (BCG) had failed. Each patient
      received a single whole bladder photodynamic therapy treatment, consisting of 2
      mg./kg. porfimer sodium intravenously followed 40 to 50 hours later by
      intravesical red light (630 nm.) at 15 J./cm.2. Post-photodynamic therapy
      evaluations included weekly telephone contact to assess acute adverse reactions,
      and assessment of efficacy and bladder toxicity at 3 months and quarterly
      thereafter. RESULTS: At initial clinical evaluation at 3 months 58% of the
      patients had a complete response as indicated by negative cystoscopy, bladder
      biopsy and urine cytology but in 42% treatment failed. At a mean followup of 12
      months (range 9 to 48) 10 of the 21 complete responders had recurrence for an
      overall durable response rate of 31%. Fourteen patients subsequently underwent
      cystectomy for persistent carcinoma in situ (12) and carcinoma in situ recurrence
      (2). Of the 36 patients 7 experienced bladder contracture. CONCLUSIONS: The
      initial results are encouraging for a single whole bladder photodynamic treatment
      of patients in whom prior intravesical therapy for carcinoma in situ has failed.
      While followup is short, porfimer sodium photodynamic therapy appears potentially
      promising as an alternative to cystectomy in patients with refractory carcinoma
      in situ.

PMID- 9628602
TI  - Long-term followup of a bladder carcinoma cohort: routine followup urography is
      not necessary.
AB  - PURPOSE: We evaluate whether routine excretory urography is needed in the long
      term followup of patients with bladder carcinoma. MATERIALS AND METHODS: A total
      of 680 patients with an initial diagnosis of bladder carcinoma from 1987 to 1988
      in western Sweden were prospectively registered and followed for at least 5
      years. All carcinomas of the kidney, renal pelvis and ureter, and all surgically
      treated cases of ureteral stricture were registered. RESULTS: During followup
      renal pelvic or ureteral carcinoma developed in 16 patients, renal cell carcinoma
      was diagnosed in 2 and 6 underwent surgery for benign obstruction of the distal
      ureter. CONCLUSIONS: The low annual incidence of malignant upper urinary tract
      and renal tumors as well as ureteral strictures supports our opinion that routine
      imaging of the upper urinary tract is not indicated during followup of patients
      with bladder carcinoma. We recommend urography at initial diagnosis of bladder
      carcinoma, when tumor progression occurs and when symptoms or signs raise
      suspicion of upper urinary tract disease.

PMID- 9628603
TI  - The female urethral sphincter: a morphological and topographical study.
AB  - PURPOSE: We reassess the anatomy and topography of the female urethral sphincter
      system and its innervation in regard to urethra sparing anterior exenteration and
      other surgical procedures. MATERIALS AND METHODS: Anatomical and histological
      studies were performed on 9 fetal specimens and 4 adult cadavers. Using graphics
      software the anatomical structures of the true pelvis were reconstructed based on
      computerized tomography cross sections and digitized histological sections. On
      the adult cadavers anterior exenteration was performed to study the implications
      of the isolated urethra and its sphincter mechanism. RESULTS: Strata of
      connective tissue were found to divide the smooth muscles of the proximal two
      thirds of the female urethra into 3 layers. Computer guided 3-dimensional
      reconstruction of digitized histological sections showed that thin fibers of the
      pelvic plexus course to this part of the urethra. The majority of these fibers
      may be preserved by carefully dissecting the bladder neck and the proximal
      portion of the urethra, leaving the lateral vaginal walls intact. The striated
      rhabdosphincter, which is innervated by fibers of the pudendal nerve, was in the
      caudal third of the urethra. CONCLUSIONS: A well-defined sphincteric structure or
      sphincter could not be anatomically recognized in the bladder neck region. The
      majority of rhabdosphincter fibers were found in the middle and caudal thirds of
      the urethra. Thus, in patients undergoing removal of the bladder neck and part of
      the proximal portion of the urethra continence can be maintained by the remaining
      urethral sphincter system, provided that innervation remains essentially intact.

PMID- 9628604
TI  - Male epispadias: experience with 45 cases.
AB  - PURPOSE: We evaluate the long-term results of surgery for isolated (without
      exstrophy) male epispadias. MATERIALS AND METHODS: A total of 45 male patients
      with isolated epispadias were treated and followed at Debrousse Hospital between
      1971 and 1993, 8 in whom repairs performed elsewhere had failed and 14 had total
      urinary incontinence. Incontinence was treated with a modified Young-Dees
      reconstruction of the bladder neck and the ureters were reimplanted in all cases.
      Long-term followup was available in 18 cases of a Cantwell-Young-Gross, 4 Duplay,
      7 full thickness skin graft, 1 bladder graft and 10 Cantwell-Ransley
      urethroplasties. Penile reconstruction was performed using a 2-stage procedure in
      8 patients (freeing of the corpora followed by urethroplasty), and an isolated
      urethroplasty in 13. All other patients underwent a single stage repair combining
      dissection of the penis and urethroplasty. RESULTS: All patients were reassessed
      clinically. Of 13 incontinent patients followed for 1 to 20 years 11 acquired
      continence, 1 remains incontinent and 1 underwent a repeat procedure recently.
      Urethroplasty was immediately satisfactory in 66% of the cases, minor
      complications developed in 25% and serious complications (especially free graft
      urethroplasty) developed in 10%. Assessment of genital cosmesis is subjective but
      it was considered acceptable in most cases. All 29 patients with long-term
      followup had erections, 24 performed regular sexual intercourse, 17 had normal
      ejaculations and 4 fathered children. CONCLUSIONS: The principles described by
      Cantwell-Young and Gross, and modified by Ransley, have considerably improved
      penile reconstruction. Free graft and Duplay urethroplasties provided
      unacceptable results in our series. Our results of surgery for incontinence
      associated with isolated male epispadias (84%) were better than for male
      exstrophy (63%).

PMID- 9628605
TI  - Laser treatment of large cavernous hemangiomas of the penis.
AB  - PURPOSE: Cavernous hemangiomas of the penis are rare benign tumors commonly
      excised for cosmesis and bleeding. Reports of laser treatment of these lesions
      with the patient under local anesthesia indicate good functional and cosmetic
      results. We report our experience with 4 cavernous hemangiomas treated with the
      neodymium:YAG laser. MATERIALS AND METHODS: Four patients, 8, 16, 31 and 50 years
      old, had a total of 8 hemangiomas, which were treated with the neodymium:YAG
      laser at 5 to 15 watts of power for 3-second pulse durations. RESULTS: All
      patients had excellent cosmetic and functional results. These treatments were
      done with essentially no blood loss, on an outpatient basis and without
      complications. CONCLUSIONS: The treatment of choice for hemangiomas of the penis
      in the pediatric and adult population is neodymium:YAG laser coagulation.

PMID- 9628606
TI  - The correlation among cavernous pressure, penile rigidity and resistance index.
AB  - PURPOSE: We define the precise meaning and diagnostic significance of the
      resistance index generated by duplex scanning. MATERIALS AND METHODS: In 80
      patients penile rigidity was clinically evaluated and a penile duplex scan was
      performed after intracavernous injection of 10 microg. prostaglandin E1. The
      intracavernous equilibrium pressure was measured in 34 of these patients.
      RESULTS: We found a statistically highly significant linear relationship among
      cavernous pressure, resistance index and penile rigidity (p <0.001). CONCLUSIONS:
      The resistance index and clinical degree of penile rigidity are 2 expressions of
      intracavernous pressure. Clinical observation of erection is equivalent to the
      resistance index in screening for cavernous leakage.

PMID- 9628607
TI  - Buckling of cylinders may cause prolonged penile pain after prosthesis
      implantation: a case control study using magnetic resonance imaging of the penis.
AB  - PURPOSE: We identify risk factors associated with chronic postoperative penile
      pain after inflatable prosthesis insertion. MATERIALS AND METHODS: We performed a
      case control study to determine the incidence of prolonged penile pain in 65 men
      who underwent prosthesis insertion. The association of various potential risk
      factors, including diabetes mellitus, incision site, prosthesis type, patient age
      and history of pelvic surgery, was assessed. In addition, the penis was examined
      for physical findings, and penile magnetic resonance imaging (MRI) was done as an
      in situ evaluation of the anatomical position and functional status of the
      inflatable prosthesis. RESULTS: A total of 14 patients (21.5%) with prolonged
      pain were compared to the remaining 51 with no pain. All parameters evaluated
      were similar in both groups except for MRI findings. Of the 14 patients with pain
      12 (85.7%) had buckling of the cylinders in the flaccid state compared to only 1
      of the 51 controls (1.9%). Statistical analysis showed a highly significant
      association between buckling and penile pain (odds ratio 300, p <0.0001).
      Surgical correction of buckling resolved pain in 5 patients. CONCLUSIONS:
      Prolonged postoperative penile pain after prosthesis insertion is strongly
      associated with cylinder buckling. This buckling may be the consequence of an
      excessively long cylinder or an appropriate size cylinder that fails to reach the
      crural end. The method of accurately diagnosing these alterations is MRI of the
      penis.

PMID- 9628608
TI  - Management of benign prostatic hyperplasia in high risk patients: long-term
      experience with the Memotherm stent.
AB  - PURPOSE: Of all patients with benign prostatic hyperplasia (BPH) 10 to 15% cannot
      undergo surgery due to grave concomitant diseases. Successful treatment should
      avoid catheterization to maintain quality of life. We report on our long-term
      experience with the Memotherm* stent implanted in high risk patients with BPH.
      MATERIALS AND METHODS: The Memotherm stent is made of self expanding
      thermosensitive nitinol, and it is implanted into the prostatic urethra using
      endoscopic control. Due to its shape memory the stent reaches maximum size at
      body temperature. The method of implantation is minimally invasive and the
      treatment can be done with the patient under spinal or intravenous anesthesia.
      From March 1993 to December 1996 we implanted the Memotherm stent in 123 high
      risk patients. To assess the long-term effects we performed followups up to 48
      months after implantation. As a measure of the efficacy of the stent we
      documented urinary flow and residual urine. To assess voiding symptoms and
      quality of life we used the International Prostate Symptom Score. RESULTS:
      Implantation of the Memotherm stent led to a decrease of residual urine from a
      mean of 153.7 to 26.0 ml. and to an increase of urinary flow from 7.4 to 16.1 ml.
      per second. Patients had fewer voiding problems and noticed an increase in
      quality of life. The success of this therapy remained high during followup.
      CONCLUSIONS: Treatment with the Memotherm stent offers a good alternative therapy
      for high risk patients with BPH.

PMID- 9628609
TI  - Transition zone prostate specific antigen density: lack of use in prediction of
      prostatic carcinoma.
AB  - PURPOSE: Among the new approaches to enhance the performance of prostate specific
      antigen (PSA) testing in a biopsy population is the use of the free-to-total PSA
      as well as the transition zone density, which is calculated by dividing the PSA
      by the transition zone volume. We compare these manipulations of the PSA to PSA
      alone in a biopsy population. MATERIALS AND METHODS: We evaluated 917 consecutive
      men who underwent ultrasound guided biopsy for an elevation in serum PSA or
      abnormality on digital rectal examination. Total PSA was measured using the
      Tandem-E or Tandem-R method. Prostate gland volume and transition zone were
      measured with ultrasound and calculated using the prolate ellipsoid formula.
      RESULTS: In the overall PSA range 276 men had carcinoma (30.0% of the
      population), while in the PSA 4.0 to 10.0 ng./ml. range 141 of 477 had cancer
      (29.6%). Receiver operating characteristics analysis and analysis of variance
      were performed. In the overall PSA series the Tandem total PSA performed as well
      as any PSA index to predict carcinoma. In the restricted range of total PSA 4.0
      to 10.0 ng./ml. total PSA density as well as transition zone density were more
      predictive than PSA alone. In both PSA ranges the volume of benign glands was
      significantly larger than in the prostates exhibiting carcinoma. There was no
      statistically significant difference in outcomes of analyses between different
      investigators or different sites of investigation (Veterans Affairs versus
      university based hospitals). CONCLUSIONS: In this biopsy population transition
      zone PSA density did not add to the information available with total PSA and
      gland volume. Neither investigator nor site bias contributed to the failure of
      transition zone PSA density or PSA density to predict prostatic carcinoma.

PMID- 9628610
TI  - Serum levels of total and free prostate specific antigen in men on hemodialysis.
AB  - PURPOSE: The measurement of prostate specific antigen (PSA) is widely used in
      screening programs for early detection of prostate cancer. It has been recently
      shown that the ratio of free-to-total PSA in serum is lower in malignant than in
      nonmalignant prostatic disorders and, therefore, might be a parameter to improve
      screening specificity. We determine the influence of renal failure on serum
      levels of total and free PSA, and free-to-total PSA ratio. MATERIALS AND METHODS:
      Serum concentrations of total and free PSA, and free-to-total PSA ratio were
      measured in 93 men undergoing hemodialysis. The control group consisted of 2,298
      healthy blood donors. RESULTS: Serum levels of total PSA were not significantly
      different between control and hemodialysis patients. Serum free PSA and free-to
      total PSA ratio of hemodialysis patients were significantly higher than those of
      controls (p <0.01 to 0.001). However, these values did not change in uremic
      patients after hemodialysis. Although serum total and free PSA levels increased
      with each decade of age, they did not correlate with age in hemodialysis
      patients. CONCLUSIONS: Serum free PSA as well as total PSA is not eliminated by
      hemodialysis, and elevated levels of free PSA and free-to-total PSA ratio in
      hemodialysis patients may be caused by a concomitant decrease in binding
      proteins. The reference ranges for total and free PSA, and free-to-total PSA
      ratio may not be necessarily beneficial in hemodialysis patients.

PMID- 9628611
TI  - Predictive value of prostate specific antigen nadir after salvage cryotherapy.
AB  - PURPOSE: We determined nadir prostate specific antigen (PSA) after salvage
      cryotherapy to distinguish patients who are potentially cured from those at risk
      for subsequent biochemical and biopsy proved failure. MATERIALS AND METHODS: A
      total of 146 patients who underwent salvage cryotherapy were followed a median of
      21 months (range 3 to 47) with regular serum PSA analysis and digital rectal
      examination. Sextant biopsies were performed at 6 months or earlier when PSA
      increased greater than 2 ng./ml. from the nadir value (biochemical failure) or
      there was a palpable local recurrence. We compared the incidence of biochemical
      failure and biopsy specimens positive for cancer to pretreatment PSA and
      posttreatment nadir PSA. RESULTS: In 59 of the 146 patients (40%) PSA decreased
      to an undetectable level within a median of 3 months. In 85 of the 109 patients
      (78%) who underwent biopsy the specimens were negative for cancer. Low serum PSA
      nadir values were associated with low pretreatment PSA and a low incidence of
      biochemical failure. In 6 of 60 patients (10%) in whom PSA nadir was 0.5 ng./ml.
      or less and in 18 of 49 (37%) with a higher PSA nadir biopsy was positive for
      cancer. CONCLUSIONS: A PSA nadir of 0.5 ng./ml. or less should be achieved after
      salvage cryotherapy. Higher nadirs are more likely to be associated with
      increasing posttreatment PSA and positive biopsies. PSA nadir is a better
      prognostic indicator of biochemical and biopsy proved failure after salvage
      cryotherapy than pretreatment PSA.

PMID- 9628612
TI  - High dose combination radiotherapy for the treatment of localized prostate
      cancer.
AB  - PURPOSE: We evaluate the efficacy of high dose combination radiotherapy for the
      treatment of localized prostate cancer. MATERIALS AND METHODS: A total of 212
      patients with localized prostate cancer (T1-T3) were treated with transperineal
      radioactive seed implantation followed by 45 Gy. external beam radiation therapy.
      Patients with Gleason scores of 2-5 were treated with 125iodine at a minimum
      peripheral dose of 120 Gy., while 103palladium at a minimum peripheral dose of 90
      Gy. was used for those with Gleason scores of 7-10. Patients with Gleason 6
      diploid tumors were treated with 125iodine and those with aneuploid tumors were
      treated with 103palladium. Biochemical failure was defined as inability to
      achieve a prostate specific antigen nadir value of 0.5 ng./ml. or less. No
      patient was treated with androgen deprivation therapy. RESULTS: The 212 patients
      have a minimum of 24 months of followup (mean 33 months). Prostate specific
      antigen 0.5 ng./ml. or less was reached by 72% of the patients (152 of 212) and
      positive biopsies were detected in 13.9% (20 of 144). Using life table
      survivorship analysis the probability of initial biochemical success at 5 years
      was 91% (95% confidence interval, 83 to 97). The probability of subsequent
      failure following an initial success was 11% (95% confidence interval, 6 to 20)
      at 24 months. The complications of combination therapy included proctitis in
      21.4% (47 of 212 men), impotence in 38% (38 of 100), urinary retention in 1.5%,
      incontinence in 2.8%, rectoprostate fistula in 2.4%, rectal wall breakdown in
      0.5% and urethral stricture in 0.5%. Six patients (2.8%) required colostomy and
      urinary diversion. CONCLUSIONS: Short-term responses to high dose combination
      radiotherapy for localized prostate cancer are promising. The morbidity is
      acceptable. Further long-term followup is warranted to assess this treatment.

PMID- 9628613
TI  - Disease progression following radical prostatectomy in men with Gleason score 7
      tumor.
AB  - PURPOSE: The long-term prognosis of men with Gleason score 7 adenocarcinoma of
      the prostate is uncertain. MATERIALS AND METHODS: We studied 488 men whose
      radical prostatectomy specimen showed Gleason score 7 tumor without involvement
      of the seminal vesicles or lymph nodes. Of the 400 men without progression 318
      had been followed for 2 years or more and 93 for 7 years or more. RESULTS: Cases
      of organ confined disease and negative margins regardless of extent of
      extraprostatic extension had roughly similar and better prognoses than cases of
      focal and established extraprostatic extension with positive margins. The greater
      influence of margin status on progression (p <0.0001) compared to extent of
      extraprostatic extension (p = 0.023) was evidenced in the multivariate analysis.
      Of 30 men with established extraprostatic extension and positive margins 6 (20%)
      had progression to distant metastases, which was similar to 14 of 58 (24%)
      without established extraprostatic extension and positive margins. There was no
      difference in response to radiotherapy between men with established
      extraprostatic extension and positive margins compared to the other cases.
      CONCLUSIONS: Margins status greatly influences the risk of progression in men
      with Gleason score 7 tumors. Among men with Gleason score 7 tumors, except for
      those with established extraprostatic extension and positive margins, more than
      50% appear to be cured at long-term followup. Because of the high risk of
      progression in patients with positive margins, clinical studies of adjuvant
      therapy in this population appear warranted.

PMID- 9628614
TI  - Postoperative chronic pain and bladder dysfunction: windup and neuronal
      plasticity--do we need a more neurological approach in pelvic surgery?
AB  - PURPOSE: Cases of combined symptoms of dysfunctional voiding and associated
      pelvic discomfort are difficult diagnostic and therapeutic challenges. Surgical
      solutions not uncommonly fail to relieve those symptoms. We determine why these
      symptoms persist postoperatively. MATERIALS AND METHODS: Four cases of ureteral
      injury during gynecological laparoscopic procedures for pelvic/menstrual pain are
      presented. The cases are reviewed for their severity and similarity in presenting
      symptoms, complications and long-term consequences. RESULTS: In all cases light
      pain symptoms and/or dysfunctional voiding problems that existed before the
      initial surgery escalated severely after corrective pelvic surgery. CONCLUSIONS:
      There are established neurophysiological mechanisms that would explain the
      observed increase in pain after surgical manipulation of the pelvis. Windup and
      changes in neuronal plasticity are direct consequences of wounding and/or neural
      injury to the central nervous system. These principles are important for surgeons
      to appreciate due to the impact they can have on the outcomes of surgery.
      Blocking the sensory input into the spinal cord, inherent to every surgical
      procedure, through use of local anesthetics, that is preemptive anesthesia,
      before creation of a wound provides the greatest protection against escalation of
      symptoms. Thorough evaluation of all patients before pelvic surgery is
      recommended to identify high risk groups (preexisting pain, voiding syndromes).

PMID- 9628615
TI  - Vesicourethral dysfunction associated with multiple sclerosis: clinical and
      urodynamic perspectives.
AB  - PURPOSE: We investigate the association of clinical and urodynamic findings with
      corresponding clinical grade and possible predictors of clinical grade of
      multiple sclerosis (MS). MATERIALS AND METHODS: A total of 90 patients, 28 to 62
      years old (mean age 45.8 +/- 12.1), with the clinical syndrome of MS were
      consecutively and prospectively studied. All patients were subjected to detailed
      video urodynamic evaluation and electromyography of the external urethral
      sphincter. RESULTS: Urodynamic evaluation revealed detrusor hyperreflexia in 52
      patients (57.7%), detrusor external sphincter dyssynergia in 27 (30%) and
      hypocontractility or areflexia of the detrusor in 15 (16.6%). Residual urine
      varied widely from 50 to 900 ml. Decreased compliance with areflexia was seen in
      5 patients (5.5%) and nonrelaxing sphincter (but not contracting) with bladder
      hypercontractility was noted in 9 (10%). Statistical analysis followed comparison
      of 2 proportions. When patients with a less severe form (grades 1 and 2) were
      differentiated from those with a more severe form of MS (grade 3), we observed a
      significant difference only in incontinence, high post-void residual, leg
      spasticity, urinary stones, hydronephrosis, type 3 detrusor external sphincter
      dyssynergia, no electromyography activity and positive sharp waves. The variables
      with the highest predictive value between the groups were urinary stones, sepsis,
      type 3 detrusor external sphincter dyssynergia and no electromyography activity
      of the external urethral sphincter (100%). CONCLUSIONS: Proper identification of
      the bladder and external urethral sphincter status, especially exclusion of
      detrusor overactivity or a dyssynergic response of the external urethral
      sphincter, will prevent complications that may result in deterioration of quality
      of life.

PMID- 9628616
TI  - A serous lined antireflux valve: in vivo fluorourodynamic evaluation of
      antireflux continence mechanism.
AB  - PURPOSE: We evaluate the fluoroscopic and urodynamic performance of a new serosal
      lined antireflux continence valve (T pouch valve) using an in vivo animal model.
      MATERIALS AND METHODS: Intestinal reservoirs were constructed using an in vivo
      pig model. Multiple serosal lined valves of varying diameters and tunnel lengths
      were evaluated in the acute (immediately after construction) and chronic (4 weeks
      postoperatively) settings. Video fluorourodynamic evaluations were performed to
      identify valve leak point pressures and optimal tunnel length-to-luminal diameter
      ratios. RESULTS: Four serosal lined valves tapered to a diameter of 18 and 30F in
      1 and 2 cm. tunnels were evaluated. Immediately following construction of the
      valves no leakage was observed during reservoir filling (maximal pressure 50 cm.
      water) or external compression maneuvers to simulate a Valsalva maneuver (maximal
      intra-reservoir pressure 100 cm. water). Identical fluorourodynamic studies
      performed after a 4-week recuperation demonstrated leakage through the 30F, 1 cm.
      tunnel valve during reservoir filling (intra-reservoir pressure 19 cm. water).
      Increasing the tunnel length of the 30F system to 2 cm. (tunnel length-to-luminal
      diameter ratio 2:1) eliminated all evidence of valve leakage up to a maximal
      intra-reservoir pressure of 100 cm. water. CONCLUSIONS: These studies demonstrate
      the urodynamic characteristics of a new serosal lined valve. This easily
      constructed mechanism serves as a reliable antireflux (afferent) or continence
      (efferent) system.

PMID- 9628617
TI  - Unilateral adrenal heterotopia with renal-adrenal fusion.

PMID- 9628618
TI  - Focal xanthogranulomatous pyelonephritis presenting as a renal tumor with vena
      caval thrombus.

PMID- 9628620
TI  - Laparoscopic ureteroureterostomy for retrocaval ureter.

PMID- 9628619
TI  - Ureteropelvic junction obstruction presenting as acute pancreatitis.

PMID- 9628621
TI  - Sarcoidosis in a young woman with bladder carcinoma.

PMID- 9628622
TI  - Multifocal transitional cell cancer and p53 mutation analysis.

PMID- 9628623
TI  - Posterior urethral valves presenting as post-ejaculatory dysuria in a 29-year-old
      physician.

PMID- 9628624
TI  - Late appearance of Cowper's syringocele.

PMID- 9628625
TI  - Testicular infarction associated with sickle cell disease.

PMID- 9628626
TI  - Interstitial pneumonitis following bicalutamide treatment for prostate cancer.

PMID- 9628627
TI  - Re: Editorial: Data interpretation and integration of new tests into clinical
      practice.

PMID- 9628628
TI  - Re: Editorial: Data interpretation and integration of new tests into clinical
      practice.

PMID- 9628629
TI  - Re: Treatment results using pubovaginal slings in patients with large cystoceles
      and stress incontinence.

PMID- 9628630
TI  - Re: Prostate tissue composition and response to finasteride in men with
      symptomatic benign prostatic hyperplasia.

PMID- 9628631
TI  - Re: Advances in angiogenesis research: relevance to urological oncology.

PMID- 9628632
TI  - Re: Prostate cancer in Nigerians: facts and nonfacts.

PMID- 9628633
TI  - Re: The history of urology on postage stamps and cancellations.

PMID- 9628634
TI  - Are pediatric patients more susceptible to major renal injury from blunt trauma?
      A comparative study.
AB  - PURPOSE: We determine whether pediatric patients are more susceptible to major
      renal injury than adults. MATERIALS AND METHODS: We retrospectively reviewed the
      medical records of 34 consecutive children 2 to 17 years old (mean age 10) and 35
      consecutive adults 19 to 59 years old (mean age 32) with blunt renal trauma who
      presented to our 2 level I trauma centers between 1990 and 1996. Patients with
      incomplete charts were excluded from study. According to the organ injury scaling
      committee of the American Association for the Surgery of Trauma renal injuries
      were graded based on computerized tomography results or laparotomy findings (4
      adults) with major injuries classified as grade IV or V. Vascular injuries were
      excluded from study. Injury severity scores were calculated using the abbreviated
      injury scale. RESULTS: Injury severity scores ranged from 4 to 75 (mean 16) in
      the pediatric and 5 to 50 (mean 22) in the adult populations (p <0.01). Overall
      16 of the 34 children (47%) and 8 of the 35 adults (23%) sustained major renal
      injuries (p <0.04). In 4 children who required surgical exploration for
      hemodynamic instability injury severity score ranged from 17 to 42 (mean 26) and
      all had major renal injuries. In 7 of the 35 adults (20%) who underwent surgical
      exploration because of hemodynamic instability and/or positive diagnostic
      peritoneal lavage injury severity score ranged from 22 to 50 (mean 34). Three of
      these 7 adults (42%) had major renal injuries and all had other visceral injuries
      at exploration. CONCLUSIONS: Children are more likely than adults to sustain
      renal injury from blunt abdominal trauma.

PMID- 9628635
TI  - Renal lesion growth in children with tuberous sclerosis complex.
AB  - PURPOSE: Renal lesions, including angiomyolipoma, renal cysts (simple and
      polycystic kidney disease) and renal cell carcinoma, develop in patients with
      tuberous sclerosis complex. While there is limited information that these lesions
      may grow in adults with tuberous sclerosis complex, the incidence,
      characterization and growth rate in children have not been reported. Also, the
      age at which these lesions first appear, thus providing insight into their
      natural history, is unknown. We present our data from a longitudinal renal
      surveillance study of children with tuberous sclerosis complex. MATERIALS AND
      METHODS: Since 1985 children with tuberous sclerosis complex at our hospital have
      undergone periodic renal imaging by ultrasonography or computerized tomography to
      monitor renal lesions. A total of 35 girls and 25 boys 1 to 18 years old have
      undergone at least 2 or more annual renal ultrasounds. RESULTS: On initial
      evaluation 33 of 60 children (55%) (mean age 6.9 years) had an identifiable renal
      lesion, which increased to 48 of 60 (80%) at followup (mean age 10.5 years).
      Angiomyolipoma was the most frequent lesion (75%) followed by simple renal cysts
      (17%). Angiomyolipomas increased in size and/or number in 10 of 18 boys (56%) and
      18 of 27 girls (66%). The largest growth rate in 1 year was from 0 to 4 cm. and
      from 5 to 9 cm. in diameter. The youngest patient demonstrated lesions at age 2
      years. The average age at which a normal ultrasound became abnormal was 7.2
      years. While a total of 27 patients had a normal ultrasound on entering the
      study, lesions had developed in 15 at followup (11 with angiomyolipomas, 4 with
      cysts). Five patients had cysts that had disappeared at followup. A 7-year-old
      boy had a 9 cm. renal cell carcinoma removed. One patient has renal lesions
      characteristic of autosomal dominant polycystic kidney disease. CONCLUSIONS:
      Renal involvement in patients with tuberous sclerosis complex begins in infancy,
      and angiomyolipoma is the most common lesion (75%). Angiomyolipomas are more
      likely to grow than remain stable, although the rate of growth varies. Simple
      renal cysts may appear or disappear with time but angiomyolipomas do not
      disappear. An initially normal renal ultrasound does not rule out future
      development of lesions. Periodic surveillance is indicated in children with
      tuberous sclerosis complex.

PMID- 9628636
TI  - Compensatory renal growth in the solitary kidneys of Danforth mice with genetic
      renal agenesis.
AB  - PURPOSE: Previously the upper urinary tract anatomy has been characterized in
      Danforth mice spontaneous murine mutation. This mutation results in unilateral
      renal agenesis in 30% of the heterozygous offspring. Whether compensatory renal
      growth occurs in the remaining solitary kidney was assessed. MATERIALS AND
      METHODS: Heterozygous pairs of Danforth mice were mated. Of 99 kidneys recovered
      from adult offspring (8 weeks old) 41 were fixed in Bouin's solution, weighed,
      sectioned at 8 microm., stained and prepared for morphometry. An additional 6
      kidneys recovered near term (gestational day 18) were processed in the same
      fashion. The kidneys from the mice without the mutation served as controls.
      Morphometric analyses were performed using computer software. The size and the
      distribution of glomeruli were studied. RESULTS: The kidney-to-body weight ratio
      in the mice with 2 kidneys varied between 1.286 and 2.198 (mean 1.603 +/- 0.33).
      There were 9 solitary kidneys and their weight x 2/body weight ratio varied
      between 1.744 and 3.779 (mean 2.9583 +/- 0.724). The differences between these 2
      groups were statistically significant (p = 0.003). In addition, the mean cross
      sectional areas in solitary kidney glomeruli was 13.2% greater than those in
      bilateral kidneys. CONCLUSIONS: Previously described models of compensatory renal
      growth relied on surgically inducing varying degrees of renal ablation in intact
      animals with 2 kidneys, which introduced numerous variables in the study of a
      complex problem. The results demonstrate that the naturally occurring solitary
      kidneys of the Danforth mice undergo compensatory renal growth. Furthermore, this
      growth is initiated early in utero. The lack of anesthetic and surgical
      manipulation may make this an attractive, reliable and readily available model
      for the study of compensatory renal, including in utero, growth.

PMID- 9628637
TI  - The urodynamic relationship of renal pelvic and bladder pressures, and urinary
      flow rate in rats with congenital vesicoureteral reflux.
AB  - PURPOSE: We define the relationship of renal pelvic and bladder pressures with
      varying urinary flow rates and bladder fullness in unobstructed rats with and
      without vesicoureteral reflux. MATERIALS AND METHODS: Sprague-Dawley rats (180 to
      250 gm.) were evaluated for vesicoureteral reflux followed by simultaneous and
      continuous renal pelvic and bladder pressure monitoring during bladder filling
      cycles. RESULTS: The incidence of congenital right vesicoureteral reflux was 25%
      (14 of 57 rats, below bladder pressure of 40 cm. water). The renal pelvic
      pressure was significantly higher in rats with reflux compared to normal rats
      only at very low urine output when the bladder was 90% full or greater and when
      the urine output was moderate with the bladder 50% full or less. For all other
      urine outputs and degrees of bladder fullness, there were no significant
      differences in pelvic pressure between rats with and without reflux. CONCLUSIONS:
      Renal pelvic pressures in the refluxing and nonrefluxing collecting system of
      rats with mild to moderate reflux do not differ except under well-defined
      conditions. Reflux can be induced by raising the intravesical pressure when the
      urinary flow rate is very low. Furthermore, vesicoureteral reflux pressures
      decrease post mortem. Therefore, the observation of vesicoureteral reflux is a
      relative phenomenon defined by urinary flow rate, bladder pressure and in vivo
      conditions, and one must define the specific bladder pressure and urinary flow
      rate that are present when reflux occurs. These data help explain why the
      observation of reflux may be intermittent or transient during various imaging
      studies.

PMID- 9628638
TI  - Ureteral-sciatic hernia in a child demonstrated by voiding cystography.

PMID- 9628639
TI  - Risperidone associated hemorrhagic cystitis.

PMID- 9628640
TI  - Use of the perineal and perineal-abdominal (transpubic) approach for delayed
      management of pelvic fracture urethral obliterative strictures in children: long
      term outcome.
AB  - PURPOSE: The results of 2 surgical approaches to restore urethral continuity in
      children with pelvic fracture urethral obliterative strictures were
      retrospectively reviewed. MATERIALS AND METHODS: From 1980 to 1995, 30 boys 3.8
      to 15.4 years old (median age 8.4) with urethral distraction injuries associated
      with pelvic fracture were treated with delayed 1-stage anastomotic repair.
      Surgical access was perineal in 15 cases and perineal-abdominal (transpubic) in
      15. There were also associated injuries in 13 patients, including bladder neck
      laceration in 3. Overall postoperative followup ranged from 2 to 17 years (median
      8.5). RESULTS: The stricture-free rate of 1-stage anastomotic repair with
      perineal and perineal-transpubic access was 84 and 100%, respectively. Four
      recurrent strictures were treated successfully with additional perineal
      transpubic anastomotic urethroplasty in 3 patients and internal urethrotomy in 1.
      Urinary incontinence developed in 1 boy in the perineal group and in 3 in the
      transpubic group. Retrospectively associated bladder neck injury was related to
      the original trauma in 3 of the 4 incontinent boys. The remaining child had
      overflow incontinence due to an acontractile detrusor. On review 3 of the 4
      incontinent patients had severe, unstable type IV pelvic fractures. CONCLUSIONS:
      Children with urethral distraction injuries associated with pelvic fracture
      require perineal-transpubic exposure when urethral obliterations of 3 cm. or
      greater develop or local complications are present in the affected area, making
      it impossible to create a tension-free, spatulated epithelium-to-epithelium
      anastomosis to restore urethral continuity via the perineal route. This study
      also supports previous reports that suggest a relationship of urinary
      incontinence and associated bladder neck injury with severe pelvic fracture
      rather than with delayed urethral repair.

PMID- 9628641
TI  - Urethral metastasis in Wilms tumor.

PMID- 9628642
TI  - Changes in nocturnal bladder capacity during treatment with the bell and pad for
      monosymptomatic nocturnal enuresis.
AB  - PURPOSE: We examined changes in nocturnal urine production and bladder capacity
      in enuretic children during bell and pad treatment. MATERIALS AND METHODS: A
      total of 18 children 7 to 11 years old with severe nocturnal enuresis had
      nocturnal urine production measured for a 14-day baseline period, which included
      daytime voidings on weekends. Thereafter, a 6-week treatment with the bell and
      pad was initiated, and nocturnal urine production and bladder capacity were
      monitored. RESULTS: Of 18 patients 10 became dry. Maximum daytime bladder
      capacities before treatment were fairly normal with no indication of treatment
      outcome. At the beginning of treatment maximum nocturnal bladder capacity was
      smaller than maximum daytime bladder capacity and during treatment it increased
      gradually. An increase in bladder volume during the enuretic episode was noted as
      well. No overall changes were found for nocturnal urine production. CONCLUSIONS:
      Treatment with the bell and pad is associated with a significant increase in
      nocturnal bladder capacity, in children who became dry and in those who remained
      wet. This increase explains why after attaining dryness the children were able to
      sleep through the night instead of having nocturia.

PMID- 9628643
TI  - Management of urethral strictures after hypospadias repair.
AB  - PURPOSE: We conducted a retrospective study of patients with strictures after
      hypospadias repair to identify factors contributing to the development of
      strictures and to attempt to define an optimal strategy for management. MATERIALS
      AND METHODS: Patients with the diagnosis of hypospadias who had undergone direct
      vision internal urethrotomy, urethral dilation or urethroplasty were identified.
      The original location of the meatus, type of initial repair, subsequent
      procedures and outcome of the interventions were recorded. RESULTS: A total of 38
      patients were identified. Of the 29 patients who were initially treated with
      direct vision internal urethrotomy or urethral dilation 23 (79%) ultimately
      required open urethroplasty and did well. Of the 8 patients treated with initial
      urethroplasty 7 had successful outcomes. Overall success, defined as asymptomatic
      voiding without fistula or residual stricture, was 78% at a mean followup of 6.3
      years. CONCLUSIONS: Stricture disease continues to be a significant complication
      of hypospadias reconstruction. Initial therapy should be urethral dilation but it
      should be recognized that the majority of these patients will ultimately require
      open urethroplasty.

PMID- 9628644
TI  - Multicenter experience with the Mitchell technique for epispadias repair.
AB  - PURPOSE: We present a multicenter experience using the Mitchell epispadias
      technique to determine if satisfactory results could be obtained by various
      pediatric urologists at multiple centers using the same technique to repair
      epispadias. This particular technique involves complete disassembly of the penis
      into 2 separate hemicorporeal glandular bodies and a separate urethral plate, and
      relies on the unique blood supply to the epispadiac phallus. MATERIALS AND
      METHODS: A total of 17 boys 11 months to 21 years old underwent the Mitchell
      procedure for epispadias at 4 institutions by 6 different surgeons between 1994
      and 1996. One patient in this group had undergone prior epispadias repair, which
      had failed. RESULTS: At followup (mean 13.5 months) 3 boys had pinpoint penopubic
      fistulas, which resolved spontaneously in 2. The 21-year-old patient had a
      complete wound dehiscence. All boys with intact repairs have straight erections,
      orthotopic meatus and satisfactory appearances. There were 15 boys with a conical
      glans appearance and 1 exhibiting glandular disproportion. There was 1 episode of
      postoperative pyelonephritis. CONCLUSIONS: The Mitchell technique for repair of
      epispadias is reproducible and successful in the hands of pediatric urologists
      from different centers. Chordee is reliably corrected, erectile function
      preserved, the urethra ventrally situated in an anatomically precise fashion and
      satisfactory cosmesis achieved.

PMID- 9628645
TI  - Evolution of epispadias repair--timing, techniques and results.

PMID- 9628646
TI  - Microsurgical repair of the adolescent varicocele.
AB  - PURPOSE: Since clinically apparent varicoceles may affect testicular volume and
      sperm production, early repair has been advocated. However, repair of the
      pediatric varicocele with conventional nonmagnified techniques may result in
      persistence of the varicocele after up to 16% of these procedures. Also
      testicular artery injury and postoperative hydrocele formation can occur after
      nonmagnified repair. The microsurgical technique has been successfully completed
      in a large series of adults with a dramatic reduction in complication and
      recurrence rates. We report our experience with the microsurgical technique in
      boys. MATERIALS AND METHODS: A total of 30 boys (average age 15.9 years)
      underwent 42 microsurgical varicocelectomies (12 bilateral). All patients had a
      large left varicocele. Indications for repair included testicular atrophy (size
      difference between testicles of greater than 2 ml.) in 20 boys, pain in 5 and a
      large varicocele without pain or testicular atrophy in 5. Six boys were referred
      following failure of conventional nonmicrosurgical techniques. All boys were
      examined no sooner than 1 month postoperatively (mean followup 12). RESULTS:
      Preoperative volume of the affected testis averaged 13.0 ml., and an average size
      discrepancy between testicles of 2.8 ml. was noted before unilateral
      varicocelectomy. No cases of persistent or recurrent varicoceles were detected,
      and 1 postoperative hydrocele resolved spontaneously. After unilateral
      varicocelectomy the treated testes grew an average of 50.1%, while the
      contralateral testes grew only 23%. Overall, 89% of patients with testicular
      atrophy demonstrated reversal of testicular growth retardation after unilateral
      varicocelectomy. In contrast, both testes showed similar growth rates after
      bilateral varicocelectomy (45% left testis, 39% right testis). CONCLUSIONS: The
      meticulous dissection necessary to preserve arterial and lymphatic supply, and to
      ligate all spermatic veins in the pediatric patient is readily accomplished using
      a microsurgical approach, and results in low recurrence and complication rates.
      Rapid catch-up growth of the affected testis after microsurgical varicocelectomy
      suggests that intervention during adolescence is effective and warranted.

PMID- 9628647
TI  - Hemangioma presenting as an ulceration of the scrotum.

PMID- 9628648
TI  - Bilateral congenital cysts of the seminal vesicle with bilateral duplex kidneys.

PMID- 9628649
TI  - Vaginal construction in children.
AB  - PURPOSE: We evaluated outcomes in 20 patients 1 to 21 years old who underwent
      vaginal construction between 1980 and 1996. MATERIALS AND METHODS: A total of 21
      vaginal constructions was performed in 20 children using ileum in 13, sigmoid
      colon in 6, bladder mucosa from a diverticulum in 1 and scrotal skin in 1. The
      diagnoses included the Mayer-Rokitansky syndrome in 6 cases, micropenis in 5,
      cloacal exstrophy in 3, penile agenesis in 3, and testicular feminization,
      classic bladder exstrophy and true hermaphroditism in 1 each. RESULTS: Patients
      treated with intestinal vaginoplasty had excellent cosmetic results without
      excessive mucous production or the need for routine dilation. The bladder mucosa
      vagina achieved good results with periodic dilation. Loss of depth developed in
      the scrotal skin vagina and it was converted to an ileal vagina. Stenosis at the
      mucocutaneous junction in 1 patient with a sigmoid and 1 with an ileal vagina was
      treated with Y-V plasty. CONCLUSIONS: Vaginal construction may be performed using
      isolated bowel segments with excellent results and minimal morbidity. We have
      found ileum to be the segment of choice in younger patients, while sigmoid colon
      is preferred for vaginal construction in adolescents. Vaginal construction with
      isolated bowel segments provides a cosmetic, self-lubricating neovagina with low
      rates of failure and revision, and without the need for routine dilation.

PMID- 9628650
TI  - Characterization, localization and distribution of alpha1 adrenoceptor subtype in
      male rabbit urethra.
AB  - PURPOSE: The subtype specificity, localization and distribution of urethral
      alpha1-adrenoceptors were studied in the male rabbit urethra. MATERIALS AND
      METHODS: The properties of the urethral alpha1-adrenoceptors were investigated
      using radioligand receptor binding and light microscopic autoradiography with
      [125I]iodo-2-[b-(4-hydroxyphenyl)-ethylaminomethyl]tetralone (HEAT), and
      immunohistochemistry with monoclonal anti-alpha smooth muscle actin and anti
      alpha sarcomeric actin antibodies. RESULTS: Saturation experiments with
      [125I]HEAT demonstrated the presence of significant amounts of a single high
      affinity binding site for alpha1 adrenoceptors in the male rabbit urethra. The
      pharmacological profile of the alpha1 adrenoceptors in rabbit urethra, determined
      by inhibition experiments with subtype selective alpha1 adrenoceptor antagonists,
      was characterized by the following rank order of potency of inhibition constants
      (Ki values): prazosin < or = WB 4101 < spiperone < 5-methylurapidil < BMY 7378.
      The pKi values for the rabbit urethra were correlated with the pKi values for rat
      spleen, submaxillary glands, and vas deferens and for those reported for cloned
      alpha1d receptors with correlation coefficients of 0.68, 0.929, 0.909, and 0.523,
      respectively. CONCLUSIONS: The pharmacological characterization demonstrates the
      predominance of alpha1A or alpha1A + alpha1B adrenoceptor subtype(s) in male
      rabbit urethral smooth muscle. Furthermore, the autoradiographic and
      immunohistochemical studies show a heterogeneous distribution of alpha1
      adrenoceptors along the longitudinal axis of the urethra, within the smooth
      muscle fibers, with the receptors being localized more densely in the proximal
      than in the distal urethra.

PMID- 9628651
TI  - Effect of tachykinin NK2 receptor blockade on detrusor hyperreflexia induced by
      bacterial toxin in rats.
AB  - PURPOSE: To see whether a recently characterized model of bacterial toxin-induced
      urinary bladder inflammation (Stein et al., J. Urol. 155, 1133-1138, 1996) is
      associated with detrusor hyperreflexia, and whether endogenous tachykinins acting
      through NK2 or NK1 receptors were involved in this model. MATERIALS AND METHODS:
      The bladder of urethane-anesthetized male Wistar rats was cannulated through the
      dome. Intravesical administration of protamine sulfate (PS, 10 mg./ml./rat) or
      vehicle for 1 hour was followed by the intravesical administration of E. coli
      lipopolysaccharide (LPS, 1 mg./ml./rat) or vehicle for 1 hour. Cystometries (50
      microl./min.) were performed 3.5 hours after the exposure to LPS. MEN 11,420, a
      peptide tachykinin NK2 receptor antagonist, was administered before cystometries
      or, in a separate group of animals, during cystometries. The effect of SR
      140,333, a non-peptide NK1 receptor antagonist, was also assessed in the presence
      or absence of MEN 11,420. The urodynamic effects of PS + LPS were also tested in
      capsaicin-pretreated rats. RESULTS: Unlike PS or LPS alone, the intravesical
      administration of PS + LPS induced detrusor hyperreflexia. In PS + LPS treated
      animals during nonstop cystometries, the intermicturition interval was decreased
      by about 50% as compared to vehicle-pretreated rats. A quantitatively similar
      reduction in the bladder capacity was also observed. MEN 11,420 (100 nmol./kg.,
      i.v.) restored the intermicturition interval in PS + LPS-pretreated rats at the
      level of controls by increasing the bladder capacity, whereas it had no effect in
      vehicle-pretreated rats. SR 140,333 (1 micromol./kg., i.v.) neither modified
      urodynamic parameters in controls and in PS + LPS-treated rats nor altered the
      effect of MEN 11,420 in these groups. Capsaicin pretreatment (164 micromol./kg.,
      s.c., 4-5 days before) induced a two-fold increase of the bladder capacity in
      control rats and prevented PS + LPS-induced bladder hyperreflexia. CONCLUSIONS:
      The intravesical administration of PS + LPS produces the activation of capsaicin
      sensitive afferents. Endogenous tachykinins released from these fibers act
      through NK2 receptors to induce detrusor hyperreflexia.

PMID- 9628652
TI  - Angiogenesis inhibitor TNP-470 inhibits growth and metastasis of a hormone
      independent rat prostatic carcinoma cell line.
AB  - PURPOSE: Inhibitory effects of TNP-470, a synthetic analogue of the antibiotic
      fumagillin secreted by Aspergillus fumigatus, were studied with respect to growth
      and lung metastasis of the hormone-independent rat prostatic carcinoma cell line
      AT6.3. MATERIALS AND METHODS: Rat prostatic carcinoma AT6.3 cells were implanted
      in nude mice subcutaneously. Antimetastatic and growth-inhibitory effects of TNP
      470 in vivo were examined 3 weeks after inoculation of AT6.3 cells. Direct growth
      inhibitory effect was examined by MTT assay in vitro. RESULTS: TNP-470 inhibited
      the growth of AT6.3 cells in vitro. Subcutaneously injected TNP-470 markedly
      reduced numbers and individual size of lung metastases from AT6.3 cells
      inoculated percutaneously or intravenously into male BALB/c-nu/nu mice.
      CONCLUSION: This agent, which acts as an angiogenesis inhibitor, may prove to be
      clinically useful in preventing metastasis of hormone-independent prostatic
      cancer.

PMID- 9628653
TI  - Phenotypic characterisation of the dendritic cell infiltrate in prostate cancer.
AB  - PURPOSE: To investigate whether dendritic cells (DC), which as professional
      antigen presenting cells have the capacity to stimulate immune responses against
      tumour associated antigens, are recruited into and activated within prostate
      cancer. MATERIALS AND METHODS: Immunoenzyme and immunofluorescence labelling was
      used to identify leucocyte and DC subsets within 15 cases of prostate cancer.
      Cell numbers were compared with numbers in adjacent normal prostatic tissue.
      Total DC numbers were identified as CD45+ leucocytes not coexpressing any lineage
      specific markers. The Langerhans cell (LC) subset was detected using anti CD1a
      staining and activated DC were identified by their expression of either CD83,
      CD86 or CMRF44. RESULTS: DC were found to represent a small subset of leucocytes
      present in both benign and malignant prostatic tissue. Statistically there were
      significantly less DC and LC in prostate cancer compared with normal prostatic
      tissue. While only a small subset of DC expressed markers of activation in
      prostate cancer, this was significantly more than the virtual absence of
      activated DC in normal prostatic tissue. CONCLUSIONS: This is the first time that
      DC have been studied in prostate cancer using the relatively new DC specific
      monoclonal antibodies CD83 and CMRF-44. These findings suggest that there is no
      active recruitment of DC into prostate cancer and those DC present are only
      minimally activated.

PMID- 9628654
TI  - Development of prostate-specific antigen promoter-based gene therapy for androgen
      independent human prostate cancer.
AB  - PURPOSE: The goal of this study is to develop a tissue-specific toxic gene
      therapy utilizing the prostate specific antigen (PSA) promoter for both androgen
      dependent (AD) and androgen-independent (AI) PSA-secreting prostate cancer cells.
      Ideally this gene therapy would be effective without the necessity of exposing
      the target cells to circulating androgens. MATERIALS AND METHODS: An AI subline
      of LNCaP, an AD PSA-secreting human prostate cancer cell line, C4-2, was used in
      this study. Castrated mice bearing C4-2 tumors secrete PSA. A transient
      expression experiment was used to analyze the activity of two PSA promoters, a
      5837 bp long PSA promoter and a 642 bp short PSA promoter, in C4-2 cells. A
      recombinant adenovirus (Ad-PSA-TK) carrying thymidine kinase under control of the
      long PSA promoter was generated. The tissue-specific activity of Ad-PSA-TK was
      tested in vitro and in vivo. RESULTS: The long PSA promoter had superior activity
      over short PSA promoter, and higher activity in C4-2 cells than in LNCaP cells.
      High activity of Ad-PSA-TK was observed in C4-2 cells in an androgen deprived
      condition. In vitro, Ad-PSA-TK was further demonstrated to induce marked C4-2
      cell-kill by acyclovir in medium containing 5% FBS. No cell-kill was observed in
      control WH cells (a human bladder cancer cell line). In vivo, Ad-PSA-P-TK with
      acyclovir significantly inhibited subcutaneous C4-2 tumor growth and PSA
      production in castrated animals. CONCLUSION: The 5837 bp long PSA promoter was
      active in the androgen free environment and could be used to target both androgen
      dependent and independent PSA-producing prostate cancer cells in vitro, and
      prostate tumors in castrated hosts.

PMID- 9628655
TI  - Stable overexpression of TGFbeta1 in a transitional carcinoma cell line: impact
      on fibronectin production.
AB  - INTRODUCTION: TGFbeta1 is a potent modulator of the biology of both benign and
      neoplastic cells. Exocrine TGFbeta1 has been shown to alter fibronectin
      expression of bladder carcinoma cell lines. The present study describes the
      development of a stable TGFbeta1 overexpressing transitional carcinoma cell line,
      and evaluates the impact of autocrine TGFbeta1 production on fibronectin
      expression. MATERIALS AND METHODS: The human transitional carcinoma cell line
      253J was transfected using the pcDNA3/hTGFbeta1 expression vector under control
      of the CMV promoter. TGFbeta1 mRNA expression was determined by Northern
      analysis. TGFbeta1 protein levels were analyzed by biological assay.
      Subsequently, the effect of TGFbeta1 autocrine production on fibronectin
      expression at both the mRNA and protein level was determined. Results were
      compared to cells transfected with the pcDNA3/CAT and non-transfected 253J cells.
      RESULTS: Two 253J clones which uniformly expressed TGFbeta1 mRNA at 22 and four
      fold increases relative to controls were identified. mRNA overexpression
      correlated with marked increase in biologically active TGFbeta1 protein
      production. Autocrine production of cellular TGFbeta1 showed a positive
      correlation with fibronectin expression at both the mRNA and protein levels.
      CONCLUSIONS: Autocrine expression of TGFbeta1 increases cellular fibronectin
      production in a human transitional carcinoma cell line. Therapeutic strategies
      altering urothelial production of TGFbeta1 and fibronectin may be a potential
      strategy to potentiate intravesical BCG activity.

PMID- 9628656
TI  - Abolition of cystitis-induced bladder instability by local spinal cord cooling.
AB  - PURPOSE: The efficacy of lumbosacral spinal cord cooling for the suppression of
      reflex urinary incontinence was evaluated in a rat model of cystitis-induced
      bladder instability. MATERIALS AND METHODS: In female Sprague-Dawley rats,
      overactivity of the detrusor muscle was induced by inflammation of the urinary
      bladder. Isovolumetric intravesical pressure, urethral perfusion pressure and
      electromyographic (EMG) activity of the external urethral sphincter (EUS) were
      recorded simultaneously during repetitive local cooling (-2C or +15C) and
      rewarming (to 37C) of the dorsal L6/S1 spinal cord segments. RESULTS: Mustard oil
      induced inflammation led to a marked instability of the urinary bladder without
      affecting urethral outlet functions. Local cooling of the dorsal lumbosacral
      spinal cord with temperatures of -2C as well as +15C completely abolished bladder
      voiding contractions in rats with an inflamed bladder as well as in non-inflamed
      control animals. Cooling had little effect on the EMG activity of the EUS and
      increased the urethral perfusion pressure. The suppression of detrusor reflex
      contractions was reversed within 1-7 min. after rewarming of the spinal cord.
      CONCLUSIONS: Cooling of the dorsal spinal cord at the origin of the
      parasympathetic innervation of the bladder can be used for a reversible
      suppression of bladder instability without affecting the urethral outlet. Thus,
      local spinal cord cooling may offer a suitable method to restore continence in
      cases of reflex incontinence.

PMID- 9628657
TI  - Effect of the selective phosphodiesterase type 5 inhibitor sildenafil on erectile
      dysfunction in the anesthetized dog.
AB  - PURPOSE: The effects of sildenafil, a highly selective inhibitor of cyclic
      guanosine monophosphate-specific phosphodiesterase type 5, on erectile function
      in the anesthetized dog were evaluated. MATERIALS AND METHODS: In pentobarbital
      anesthetized dogs, increases in intracavernosal pressure in the corpus cavernosum
      and penile blood flow were induced by pelvic nerve stimulation over a frequency
      range of 1 to 16 hertz. The effects of increasing doses of sildenafil on
      electrically stimulated intracavernosal pressure, penile blood flow, blood
      pressure, and heart-rate were evaluated. In parallel experiments, the effects of
      the nitric oxide synthase inhibitor N omega-Nitro-L-Arginine (L-NOArg) on these
      same parameters also were assessed. RESULTS: The effects of nerve stimulation on
      intracavernosal pressure and blood flow to the penis were blocked by L-NOArg, 0.1
      3 mg./kg., in a dose-related manner, confirming the important role of nitric
      oxide in producing erections. Sildenafil, 1-100 microg./kg administered
      intravenously, had no direct effect on intracavernosal pressure but potentiated
      the increase in intracavernosal pressure induced by nerve stimulation. This
      potentiation occurred at sildenafil plasma concentrations consistent with its
      relaxation effect on isolated human cavernosal tissue and its inhibition of
      phosphodiesterase type 5 in vitro. Sildenafil had no significant effect on blood
      pressure or heart rate. CONCLUSIONS: By inhibiting cyclic guanosine monophosphate
      specific phosphodiesterase type 5, sildenafil augments the neuronal mechanism
      responsible for penile erection. This mechanism explains the significant
      improvements reported in the rigidity and duration of erections seen in patients
      with erectile dysfunction who have been treated with oral sildenafil.

PMID- 9628658
TI  - Inhibition of tumor growth and angiogenesis by vitamin D3 agents in murine renal
      cell carcinoma.
AB  - PURPOSE: To investigate the effect of active vitamin D3(VD) agents on tumor
      growth and metastasis. MATERIALS AND METHODS: BALB/c mice were inoculated with
      murine renal cancer Renca and graded doses of 1,25-dehydrovitamin D3 or 1-
      hydrovitamin D3 were given intraperitoneally every other day beginning on day 1,
      3, or 7 and ending on day 9, 11, or 15. Direct cytocidal activity and angiogenic
      activity were evaluated by 48-hour MTT assay and by the colorimetric method,
      respectively. RESULTS: Both VD agents inhibited tumor growth and prolonged the
      life span of Renca-bearing mice in a dose-dependent manner and both suppressed
      tumor growth in athymic mice and euthymic mice with eliminated NK activity.
      Marginal body-weight loss without appreciable hypercalcemia was observed in mice
      given VD agents. When treatment was delayed on day 7, the VD agents failed to
      inhibit tumor growth. The MTT assay showed no direct cytotoxicity of VD agents on
      Renca. Tumor angiogenesis was inhibited to 46 to 30% of the control level by VD
      agents. Furthermore, VD agents reduced pulmonary and hepatic foci in the
      metastatic models. CONCLUSIONS: These results suggest that VD agents may be
      effective as a treatment for renal cell carcinoma, especially when
      micrometastases are involved.

PMID- 9628659
TI  - Camptothecin analogues/cisplatin: an effective treatment of advanced bladder
      cancer in a preclinical in vivo model system.
AB  - OBJECTIVE: To evaluate the impact of the camptothecin analogs on human TCC
      xenograft, both as monotherapy and in combination with cisplatin (CDDP).
      MATERIALS AND METHODS: Human transitional cell carcinoma (TCC) xenograft tumor
      line (DU4184) tested by subrenal capsule assay in 112 nude mice(NM-SRCA). CDDP
      and the camptothecin analogs irinotecan (CPT-11) and 9-aminocamptothecin(9-AC)
      were evaluated. RESULTS: Both of the camptothecin analogs showed significant
      short term tumor inhibition which translated into enhanced survival. Maximal
      tumor inhibition (>95%) was achieved when either of the camptothecin analogs was
      combined with CDDP with minimal host toxicity. This translated into 400% increase
      in median survival. While all controls were dead 39 days following tumor
      implantation, none of the combination treated animals had died. CONCLUSION: The
      combination of CDDP with these camptothecin analogs is an effective therapy
      against this model of advanced TCC. These observations suggest potential clinical
      value.

PMID- 9628661
TI  - Early age at diagnosis in families providing evidence of linkage to the
      hereditary prostate cancer locus (HPC1) on chromosome 1.

PMID- 9628662
TI  - Intermittent androgen deprivation for clinically localized prostate cancer:
      initial experience.

PMID- 9628660
TI  - Sildenafil, a type-5 CGMP phosphodiesterase inhibitor, specifically amplifies
      endogenous cGMP-dependent relaxation in rabbit corpus cavernosum smooth muscle in
      vitro.
AB  - PURPOSE: The primary mechanism for relaxation of corpus cavernosum smooth muscle
      (CCSM) and penile erection depends upon nitric oxide (NO)-induced elevation of
      myoplasmic cyclic guanosine monophosphate (cGMP). Agents that enhance the NO-cGMP
      signal transduction pathway may prove beneficial in treating erectile
      dysfunction. Sildenafil, a selective type-5 cGMP phosphodiesterase inhibitor, was
      investigated to determine the specific mechanism(s) involved in the therapeutic
      use of this compound to treat impotence. MATERIALS AND METHODS: Isolated strips
      of rabbit corpus cavernosum were stimulated isometrically with phenylephrine.
      Graded relaxations were induced using various concentrations of sodium
      nitroprusside (SNP) alone and in combination with sildenafil. At fixed times, the
      tissues were rapidly frozen and processed for myosin light chain (MLC)
      phosphorylation using isoelectric focusing with Western blot analysis, and cGMP
      content using radioimmunoassay techniques. RESULTS: Sildenafil alone reduced
      spontaneous tone in unstimulated CCSM, but had little effect on phenylephrine
      induced isometric tension in the absence of a NO donor (SNP). Sildenafil
      sensitized the tissue to SNP for relaxation, but the relationship between
      relaxation and [cGMP] was unchanged by sildenafil. Relaxation from peak isometric
      force was correlated with [cGMP] but not MLC phosphorylation. CONCLUSIONS:
      Sildenafil relaxes CCSM by amplifying the effects of the normal, endogenous cGMP
      dependent relaxation mechanisms.

PMID- 9628663
TI  - Bacterial urinary tract infections in diabetes.

PMID- 9628664
TI  - Esophageal replacement for end-stage benign esophageal disease.
AB  - BACKGROUND: Benign esophageal diseases constitute a common group of disorders
      that are generally managed with medical therapy or surgery designed to improve
      foregut function. A small subset of patients, however, has advanced disease that
      requires esophageal replacement to achieve symptomatic relief. PATIENTS AND
      METHODS: One hundred four patients with benign esophageal disease who underwent
      esophageal reconstruction over a 21-year period (1975 to 1996) were reviewed
      retrospectively. Dysphagia was the major symptom driving surgery in 80% of the
      patients. Colon was used to reconstruct the esophagus in 85 patients; stomach, in
      10 patients; and jejunum, in 9 patients. Forty-two patients who had lived with
      their reconstruction for 1 year or more answered a postoperative questionnaire
      concerning their long-term functional outcome. RESULTS: In the 104 patients, the
      primary underlying abnormality leading to esophageal replacement was end-stage
      gastroesophageal reflux (37 patients), an advanced motility disorder (37
      patients), traumatic, iatrogenic or spontaneous perforation (15 patients),
      corrosive injury (8 patients), congenital abnormality (6 patients), or extensive
      leiomyoma (1 patient). Ninety-eight percent of patients reported that the
      operation had cured or improved the symptom driving surgery. Ninety-three percent
      were satisfied with the outcome of the operation. The overall hospital mortality
      rate was 2%, and the median hospital stay was 17 days. Graft necrosis occurred in
      3% of patients, and anastomotic leak occurred in 6% of patients (or 2% of the
      total number of anastomoses). CONCLUSIONS: Esophageal replacement for benign
      disease can be accomplished with a low mortality rate and a marked improvement in
      alimentation. Reconstruction restores the pleasure of eating and is viewed by the
      patient to be highly successful.

PMID- 9628665
TI  - The utility of the pectoralis myocutaneous flap in the management of select
      cervical esophageal anastomotic complications.
AB  - OBJECTIVE: The majority of cervical esophageal anastomotic complications can be
      successfully managed nonoperatively. A small group of patients may have
      anastomotic strictures or leakage and fistula formation that are chronic and
      resistant to nonoperative therapy. The purpose of this study was to review our
      experience with the use of the pectoralis myocutaneous flap to treat these
      patients. METHODS: Since April 1992, four patients have undergone pectoralis
      myocutaneous flap repair of cervical esophageal anastomotic complications at our
      institution. Two patients had chronic strictures, one patient underwent
      prophylactic repair with a pectoralis myocutaneous flap to prevent stricture
      formation, and one patient had a chronic anastomotic fistula. The pectoralis
      myocutaneous flap was harvested in the standard fashion. The technique of
      anastomotic repair is described. The medical records were retrospectively
      reviewed to determine patient characteristics and our results. RESULTS: Two
      suture line leaks developed: one small, contained leak required no intervention,
      and the other resolved with cervical drainage. Pneumonia, seroma at the site of
      the pectoralis myocutaneous flap donor, transient hoarseness, and partial skin
      graft loss occurred in one case each. There were no deaths. Hospital stay ranged
      from 12 to 22 days. A good functional result was obtained in three patients.
      CONCLUSION: Our results show that pectoralis myocutaneous flap repair of select
      cervical anastomotic complications is safe and well tolerated even in patients
      with complicated problems.

PMID- 9628666
TI  - Geometric mismatch of pulmonary and aortic anuli in children undergoing the Ross
      procedure: implications for surgical management and autograft valve function.
AB  - BACKGROUND: There is often substantial mismatch between the diameters of the
      pulmonary and aortic anuli in young patients with systemic outflow tract disease.
      To implant the autologous pulmonary valve in the aortic position under such
      circumstances, it is necessary to adapt the geometry of the systemic outflow
      tract. The effects of such adaptations on autograft function in children are not
      well known. METHODS: To determine factors predictive of autograft regurgitation,
      we analyzed 41 cases of children who have undergone the Ross procedure. The
      diameter of the pulmonary valve was greater (by at least 3 mm) than that of the
      aortic valve in 20 cases, equal (within 2 mm) in 12 cases, and less (by at least
      3 mm) in nine cases, with differences ranging from +10 to -12 mm. In 12 patients
      with a larger pulmonary anulus, aortoventriculoplasty was used to correct the
      mismatch. In patients with a larger aortic anulus, the mismatch was corrected by
      gradual adjustment along the circumference of the autograft, rather than by
      tailoring of the native aortic anulus. RESULTS: At follow-up (median 31 months),
      two patients had undergone reoperation on the neoaortic valve for moderate
      regurgitation. In the remaining 38 cases, autograft regurgitation was as follows:
      none or trivial in 30, mild in seven, and moderate in one. There was no
      correlation between regurgitation and age, geometric mismatch, or previous or
      concurrent procedures. CONCLUSIONS: Subtle technical factors that may result in
      distortion of the valve complex are probably more important determinants of
      autograft regurgitation than are indication for repair, geometric mismatch, or
      previous or concomitant outflow tract procedures. Significant mismatch of the
      semilunar anuli is not a contraindication to the Ross procedure in children.

PMID- 9628667
TI  - Disproportionate enlargement of the pulmonary autograft in the aortic position in
      the growing pig.
AB  - PURPOSE: This study was aimed to demonstrate growth in the pulmonary autograft
      after transplantation to the aortic position. METHODS AND MATERIALS: In 20
      piglets (weight 25.4 +/- 3.5 kg) (mean +/- standard deviation) a Ross operation
      was performed and in five piglets (weight 9.3 +/- 0.7 kg) (mean +/- standard
      deviation) the ascending aorta was replaced with a valveless pulmonary autograft.
      Animals were allowed to grow as much as possible. Postmortem explanted autografts
      were studied by direct measurements of the valve cusps in the Ross group and of
      the wall segments in the valveless autograft group. Measurements of the first
      group were compared with the values of a separate control group, and values of
      the second group were compared with values of samples taken at operation.
      RESULTS: In the Ross group, cuspal weight, height, and width increased
      significantly by comparison with body weight (p < or = 0.003). The rate of
      increase did not differ significantly from that of the control group with a
      native pulmonary valve. However, there was a rapid adaptation of the autograft
      valves resulting in a significantly higher mean cuspal weight, height, and width.
      In the valveless autograft group, wall circumference, thickness, and height
      increased significantly (p < or = 0.001). The circumference increased
      significantly more than that of the native pulmonary wall. Compared with the
      native aortic wall, the pulmonary autograft media showed retained pulmonary
      architecture on microscopic study. CONCLUSION: These data suggest that the
      dimensional increase of the pulmonary autograft in the aortic position in the
      growing pig is determined by growth and dilatation, that the valve mass increases
      more than that of the native pulmonary valve, and that the characteristic
      pulmonary microscopic architecture is retained.

PMID- 9628668
TI  - Seven-year follow-up of coronary artery bypasses performed with and without
      cardiopulmonary bypass.
AB  - BACKGROUND: There has been resurgent interest in coronary revascularization
      performed on the beating heart. Heretofore, there has been no long-term
      comparison of this technique to traditional coronary artery bypass with
      cardioplegia. OBJECTIVE: The purpose of this study was to provide a comparison of
      long-term survival and intervention-free outcome between patient groups subjected
      to coronary bypass accomplished with or without the use of cardiopulmonary
      bypass. METHOD: From June 1989 to July 1990, all patients treated for coronary
      revascularization by three surgeons were considered for coronary
      revascularization with the heart beating: 107 patients underwent coronary bypass
      on the beating heart, and 112 patients underwent revascularization with the aid
      of bypass with cardioplegia. Mean ages (65 +/- 10 years) and risk factors were
      identical. Patients operated on with the heart beating had 2.4 +/- 0.9 grafts
      versus 3.2 +/- 1.1 grafts for patients having cardiopulmonary bypass with
      cardioplegia. RESULTS: At 7-year follow-up, 86 of 107 (80%) patients operated on
      with the heart beating were alive versus 88 of 112 (79%) patients in whom
      cardiopulmonary bypass with cardioplegia was used. Cardiac deaths occurred in 13
      of 107 (12%) patients in the former group versus 10 of 112 (9%) patients in the
      latter group. However, 32 of 107 patients operated on with the heart beating
      (30%) needed catheterization for their symptoms versus 18 of 112 (16%) patients
      in the bypass with cardioplegia group (p = 0.01). This results in 21 of 107 (20%)
      patients in the beating heart group needing angioplasty or a second coronary
      bypass versus only 8 of 112 (7%) patients in the bypass with cardioplegia group.
      No patient in the bypass with cardioplegia group required reoperation. Most of
      the reinterventions for the beating heart group were percutaneous transluminal
      coronary angioplasty (15 of 21 [71%] patients). CONCLUSION: Despite one less
      graft per patient, survival and cardiac death rates were similar for the two
      groups. However, twice as many patients in the beating heart group required
      recatheterization (30% versus 16%), and 20% needed a second intervention. Only 7%
      of the bypass with cardioplegia group required reintervention. Limited
      revascularization of the beating heart provides long-term results comparable to
      full revascularization with cardiopulmonary bypass, but at the cost of a
      threefold increase in reinterventions.

PMID- 9628669
TI  - Long-term results of mitral valve repair for myxomatous disease with and without
      chordal replacement with expanded polytetrafluoroethylene sutures.
AB  - OBJECTIVE: This study was carried out to evaluate the long-term results of mitral
      valve repair for mitral regurgitation caused by myxomatous disease of the mitral
      valve and the late effects of chordal replacement with expanded
      polytetrafluoroethylene sutures in this operation. METHODS: A total of 324
      patients with mitral regurgitation caused by myxomatous disease underwent mitral
      valve repair from 1981 to 1995; the group comprised 241 men and 83 women whose
      mean age was 58 +/- 14 years. Chordal replacement with expanded
      polytetrafluoroethylene sutures has been performed in 165 patients since 1985.
      Most of the patients who had chordal replacement with expanded
      polytetrafluoroethylene sutures had prolapse of the anterior leaflet or prolapse
      of both leaflets, whereas most patients who had mitral valve repair without
      chordal replacement had prolapse of the posterior leaflet. Patients were followed
      up at annual intervals and had a Doppler echocardiographic study. The follow-up
      was complete and extended from 6 to 156 months (mean 36 +/- 30 months). RESULTS:
      Two operative and 21 late deaths occurred (14 cardiac and 7 noncardiac). At 10
      years the actuarial survival was 75% +/- 5%, the freedom from stroke was 94% +/-
      2%, the freedom from transient ischemic attacks was 92% +/- 4%, the freedom from
      endocarditis was 99% +/- 1%, the freedom from mitral valve reoperation was 96% +/
      1%, and the freedom from severe mitral regurgitation was 93% +/- 3%. Chordal
      replacement with expanded polytetrafluoroethylene sutures had no effect on any of
      these end points. CONCLUSIONS: Mitral valve repair was feasible in most patients
      with mitral regurgitation caused by myxomatous disease and it was associated with
      low rates of valve-related complications. Chordal replacement with expanded
      polytetrafluoroethylene had no adverse effect on the late outcome and was
      believed to have increased the probability of mitral valve repair.

PMID- 9628670
TI  - Midterm results after aortic valve replacement with freehand stentless
      xenografts: a comparison of three prostheses.
AB  - OBJECTIVE: The ideal substitute for the diseased aortic valve is yet to be found.
      For the assessment and comparison of the midterm results after aortic valve
      replacement with three different types of freehand stentless xenografts, all
      patients who underwent the operation between October 1992 and April 1997 were
      reviewed. METHODS: Of 231 patients undergoing aortic valve replacement, 106
      patients (group 1) were given the Biocor PSB (Biocor Industria e Pesquisa Ltda,
      Belo Horizonte, MG, Brazil); 76 patients (group 2) were given the Toronto SPV
      (St. Jude Medical, Inc., St. Paul, Minn.), and 49 patients (group 3) were given
      the O'Brien-Angell valve (Bravo Cardiovascular model 300, Cryolife, Inc.,
      Marietta, Ga.). The first two xenografts require inflow and outflow suturelines;
      the third xenograft needs a single-sutureline implantation. Mean age (70 +/- 6
      years; 70 +/- 7 years; 72 +/- 9 years; p = 0.6), prevalence of male sex (56
      patients, 53%; 37 patients, 49%; 22 patients, 45%; p = 0.7), of aortic stenosis
      (72 patients, 68%; 54 patients, 71%; 37 patients, 73%; p = 0.6), and need for
      associated procedures (51 patients, 48%; 30 patients, 40%; 21 patients, 43%; p =
      0.1) were comparable among groups. Mean aortic crossclamp time was shorter in
      group 3 (96 +/- 24 minutes; 100 +/- 23 minutes; 88 +/- 25 minutes;p = 0.01).
      RESULTS: Early deaths were 3 of 106 (3%) in group 1, 2 of 76 (3%) in group 2, and
      2 of 49 (4%) in group 3. Follow-up of survivors ranged from 1 to 54 months (mean
      32 +/- 13 months). Survival at 4 years was 90% +/- 3% in group 1, 95% +/- 3% in
      group 2, 85% +/- 8% in group 3 (p = 0.3). At 4 years, freedom from valve-related
      events was 95% +/- 6%, 100%, 70% +/- 8% (p = 0.004), while freedom from valve
      deterioration was 99% +/- 1%, 100%, 73% +/- 8% (p = 0.001), in group 1, 2, and 3,
      respectively (p = 0.001). At follow-up, reintervention on the xenograft was
      necessary in one patient (endocarditis) in group 1, none in group 2, and six in
      group 3 (technical cause, group 3; valve tear, group 2; pannus, group 1).
      Regression analysis showed O'Brien-Angell type of xenograft to be predictive of
      valve-related events (p = 0.02), valve deterioration (p = 0.001), and reoperation
      (p = 0.001) during follow-up. CONCLUSIONS: Midterm survival after stentless
      aortic valve replacement is good with all three xenografts. Freedom from valve
      related events, valve deterioration, and reoperation are excellent with the
      Biocor PSB or the Toronto SPV stentless valves but less satisfactory with the
      O'Brien-Angell valve.

PMID- 9628671
TI  - Long-term results of mitral-aortic valve operations.
AB  - OBJECTIVE: We analyzed the long-term morbidity and mortality of our experience
      with combined mitral-aortic surgery, as well as their determinants. METHODS:
      Among 2109 consecutive patients undergoing valve operations, 200 had mitral
      aortic valve procedures with at least implantation of a mechanical prosthesis:
      163 of 200 (81.5%) patients had double valve replacement and 37 of 200 (18.5%)
      had mitral valve repair and aortic valve replacement. All mechanical valves were
      bileaflet prostheses. Preoperatively, 171 of 200 (85.5%) patients were in New
      York Heart Association class III-IV. Event-free survivals were determined by
      means of the Kaplan-Meier method and determinants of survivals with the Cox
      proportional hazards model (p < 0.05) entering 39 preoperative and perioperative
      factors. Follow-up was complete for 96% of the patients (192/200). RESULTS:
      Overall survivals at 5, 10, and 15 years were 88.5% +/- 0.55%, 73.5% +/- 4%, and
      53.3% +/- 8.9%, and rates of freedom from valve-related mortality were 92.9% +/-
      1.5%, 85.8% +/- 3.5%, and 85.8% +/- 3.5%. The rates of freedom from permanent
      valve-related impairment were 91.5% +/- 1.7%, 85.4% +/- 3.5%, and 79.3% +/- 6.7%,
      and those from all valve-related mortality and morbidity were 74.1% +/- 2.3%,
      53.8% +/- 5%, and 49% +/- 5.6%. At last follow-up, 90% (139/154) of the survivors
      were in New York Heart Association class I-II. Left ventricular ejection fraction
      less than 50%, age older than 70 years, and preoperative ventricular arrhythmias
      were independent risk factors for valve-related late deaths. Diabetes, ejection
      fraction less than 50%, and coronary artery disease were independent determinants
      of all valve-related events. CONCLUSIONS: Functional results of survivors of
      combined mitral-aortic surgery are excellent. However long-term valve-related
      morbidity and mortality are substantial. In the patient population studied, the
      predictors are determined by patient-related factors, mainly myocardial factors,
      but not by valve-related factors.

PMID- 9628672
TI  - Delayed and selective motor neuron death after transient spinal cord ischemia: a
      role of apoptosis?
AB  - OBJECTIVE: The mechanism of spinal cord injury has been thought to be related to
      tissue ischemia, and spinal motor neuron cells are suggested to be vulnerable to
      ischemia. We hypothesized that delayed and selective motor neuron death is
      apoptosis. METHODS: Thirty-seven Japanese domesticated white rabbits weighing 2
      to 3 kg were used in this study and were divided into two subgroups: a 15-minute
      ischemia group and a sham control group. Animals were allowed to recover at
      ambient temperature and were killed at 8 hours, and 1, 2, 4, and 7 days after
      reperfusion (n = 3 at each time point). By means of this model, cell damage was
      histologically analyzed. Detection of ladders of oligonucleosomal DNA fragment
      was investigated with gel electrophoresis up to 7 days of the reperfusion.
      Immunocytochemistry, in situ terminal deoxynucleotidyl transferase-mediated
      deoxyuridine triphosphate-biotin nick-end labeling staining was also performed.
      RESULTS: After 15 minutes of ischemia, most of the motor neurons showed selective
      cell death at 7 days of reperfusion. Typical ladders of oligonucleosomal DNA
      fragments were detected at 2 days of reperfusion. Immunocytochemistry showed in
      situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate
      biotin nick-end staining was detected at 2 days of reperfusion selectively in the
      nuclei of motor neurons. CONCLUSION: These results suggest that delayed and
      selective death of the motor neuron cells after transient ischemia may not be
      necrotic but rather predominantly apoptotic.

PMID- 9628673
TI  - Feasibility of intraoperative balloon angioplasty and additional stent placement
      of isolated stenosis of the brachiocephalic trunk.
AB  - OBJECTIVE: We sought to evaluate the feasibility and results of intraoperative
      balloon angioplasty and additional stent placement of isolated stenosis of the
      brachiocephalic trunk. PATIENTS AND METHODS: Between May 1993 and October 1996,
      we treated eight patients with local stenosis of the innominate artery. Seven
      lesions were situated in the proximal and one in the middle third of the
      brachiocephalic trunk. Five patients were men and three were women, with ages
      ranging from 55 to 72 years (mean 59.5 years). All stenoses provoked severe blood
      flow reduction and caused clinical symptoms. Procedures were performed in an
      operating suite with fluoroscopic imaging capabilities. Through an anterolateral
      cervical approach the right common carotid artery was surgically exposed and then
      clamped to avoid atheroembolization during the subsequent procedure. Retrograde
      catheterization was performed to reach the stenosis of the brachiocephalic trunk.
      The lesion was dilated with a balloon catheter and successively stented. Follow
      up examinations (color-coded duplex sonography, accompanied by clinical
      inspection and systolic blood pressure) were scheduled every 6 months. RESULTS:
      In all patients the dilation of the stenosis of the innominate artery and the
      stent placement were successful without any side effects. No embolic events or
      other complications occurred. The postintervention angiography showed
      successfully dilated stenoses and patent stents in all cases. The technical
      success rate was 100%. CONCLUSIONS: On the basis of our preliminary data, we
      believe that, in selected patients, intraoperative balloon angioplasty of
      stenosis of the innominate artery with stent placement from the right common
      carotid artery approach is a safe and effective alternative to conventional
      operations.

PMID- 9628674
TI  - Verapamil plus nitroglycerin solution maximally preserves endothelial function of
      the radial artery: comparison with papaverine solution.
AB  - BACKGROUND: Endothelium plays a key role in graft patency. My colleagues and I
      have developed a verapamil+nitroglycerin solution (balanced to pH 7.4) to prepare
      the radial artery without mechanical distention or dilation and have reported the
      efficacy of its antispastic action. This study was designed to investigate
      whether using this solution as part of the University of Hong Kong protocol to
      prepare the radial artery is more efficacious than papaverine solution in
      preserving endothelial function. METHODS: Ring segments of the radial artery
      taken from 25 patients undergoing coronary artery bypass grafting were studied in
      organ chambers. The endothelium-dependent relaxation, as the index of endothelial
      function, was examined by two mechanisms-receptor-mediated relaxation (by
      acetylcholine) and non-receptor-mediated relaxation (by calcium ionophore A23187)
      in U46619-induced contraction (10 nmol/L). RESULTS: In the relaxation induced by
      either acetylcholine (27.3% +/- 5.0% [n = 7] vs 23.9% +/- 3.9% [n = 6],p = 0.6)
      or A23187 (62.9% +/- 6.0% [n = 13] vs 62.3% +/- 8.4% [n = 6],p = 0.96), there was
      no significant difference between the control radial arteries and those treated
      with the verapamil+nitroglycerin solution. In the papaverine-treated rings,
      acetylcholine-mediated relaxation was abolished (3.3% +/- 2.6% vs 23.9% +/-
      3.9%,p < 0.001) and A23187-mediated relaxation was significantly reduced (39.7%
      +/- 5.2% vs 62.3% +/- 8.4%, p = 0.02) compared with verapamil+nitroglycerin
      treatment. CONCLUSION: Use of verapamil+nitroglycerin solution to prepare the
      radial artery maximally preserves endothelial function. In contrast, papaverine
      impairs this function. Verapamil+nitroglycerin solution may be effectively and
      safely used to prepare the radial artery for coronary artery bypass grafting.

PMID- 9628676
TI  - Controlled reperfusion and pentoxifylline modulate reperfusion injury after
      single lung transplantation.
AB  - OBJECTIVE: Rodent models have suggested that initial low-pressure reperfusion of
      transplanted lungs reduces injury after ischemia. We investigated this phenomenon
      and the use of pentoxifylline in a porcine model of left single lung
      transplantation. METHODS: Donor lungs were preserved with Euro-Collins solution
      for a mean ischemic time of 18.4 hours. Neutrophil trapping in the graft,
      pulmonary artery pressure, and gas exchange were assessed over a 12-hour period.
      Partial occlusion of the contralateral pulmonary artery allowed manipulation of
      the pulmonary artery pressure in the transplanted lung. Group A (n = 5) was
      perfused at a mean pulmonary artery pressure of 20 mm Hg, group B was reperfused
      at a mean pulmonary artery pressure of 45 mm Hg for 10 minutes before reducing
      the pressure to the same as group A, and group C was reperfused at a mean
      pressure of 20 mm Hg for 10 minutes, then increased to a mean of 45 mm Hg for the
      remainder of the experiment. Group D was reperfused as in group A with the
      addition of intravenous pentoxifylline. RESULTS: Leukocyte sequestration was
      observed in the first 10 minutes after reperfusion in groups A, B, and C, with
      maximal sequestration at 2 minutes. Significantly more sequestration was observed
      in the first 6 minutes in group B than in groups A and C, which were similar.
      Pentoxifylline significantly reduced leukocyte sequestration. Pulmonary venous
      oxygen tension in the allograft lung was worst in group B. Groups A and C were
      similar, but group D was superior to all other groups (p < 0.001). CONCLUSIONS:
      Low-pressure reperfusion, even when limited to the first 10 minutes, modulates
      reperfusion injury possibly through a leukocyte-dependent mechanism. The addition
      of pentoxifylline in the recipient confers significant additional benefit.

PMID- 9628675
TI  - In elective coronary artery bypass grafting, preoperative troponin T level
      predicts the risk of myocardial infarction.
AB  - OBJECTIVE: Several combinations of risk factors for death or cardiac events after
      coronary artery bypass grafting have been described. We studied the prognostic
      value of the preoperative serum levels of cardiac troponin T. METHODS: We studied
      468 patients who underwent elective coronary artery bypass grafting. Preoperative
      and postoperative levels of cardiac troponin T and creatine kinase MB,
      electrocardiograms, clinical data, and events were recorded prospectively. No
      acute ischemic changes were present on the electrocardiogram before the
      operations, and preoperative creatine kinase MB serum levels were within normal
      limits in all patients. RESULTS: Ninety-seven (97/468, 21%) patients had serum
      levels of troponin T greater than 0.02 microg/L within 24 hours before coronary
      artery bypass grafting. Hospital mortality was similar in this group and in the
      patients with preoperative levels less than 0.02 microg/L (1% in each group).
      Nine patients (9/97, 9%) with elevated levels of troponin T before the operation
      had a perioperative myocardial infarction compared with 12 patients (12/371, 3%)
      among the group with lower troponin T levels (p = 0.015, RR = 2.9). Congestive
      heart failure occurred in 10 (10/97, 10%) and 8 (8/371,2%) patients, respectively
      (p = 0.0009, RR = 4.8). Intensive care unit (p = 0.002) and postoperative
      hospital length of stay (p = 0.09) were all longer in patients with the elevated
      preoperative troponin T level. In a logistic regression analysis, troponin T
      level before the operation was the variable most strongly correlated with
      postoperative myocardial infarction (p = 0.003). CONCLUSION: Preoperative
      troponin T stratification before coronary artery bypass grafting identifies a
      subgroup of patients with increased risk of postoperative cardiac complications.

PMID- 9628677
TI  - Prolonged discordant xenograft survival and delayed xenograft rejection in a pig
      to-baboon orthotopic cardiac xenograft model.
AB  - OBJECTIVE: Our objectives were to study delayed xenograft rejection and the
      effectiveness of pretransplantation total lymphoid irradiation combined with
      immunosuppression on rejection in a pig-to-baboon cardiac xenograft model.
      METHODS: Baboons were treated with pretransplantation total lymphoid irradiation,
      cyclosporine A (INN: ciclosporin), and methotrexate. Orthotopic pig-to-baboon
      cardiac transplantations were performed after depletion of circulating
      xenoreactive natural antibody by pretransplantation donor organ hemoperfusion.
      Tissue samples were collected for immunologic and immunopathologic evaluation.
      RESULTS: Pig cardiac xenografts survived more than 18 and 19 days without
      evidence of hyperacute rejection. Immunologic analysis of serum samples
      demonstrated that circulating xenoreactive natural antibody levels did not return
      to pretransplantation levels. The production of xenoreactive natural antibodies
      from the recipient's splenocytes was inhibited completely. Histologic examination
      of xenografts showed the feature of acute vascular rejection. Immunohistochemical
      studies demonstrated infiltration of cardiac xenografts by large numbers of
      macrophages, small numbers of natural killer cells, and a few T cells. The
      infiltrating macrophages also showed expression of interleukin-1 and tumor
      necrosis factor. Diffuse deposition of immunoglobulin G, C1Q, C3, and fibrin on
      xenograft vasculature was observed. Interleukin-2 expression was not found in
      rejected cardiac xenografts. Xenograft endothelial cells also showed evidence of
      activation (expression of cytokines interleukin-1 and tumor necrosis factor).
      CONCLUSIONS: This study demonstrates prolonged discordant cardiac xenograft
      survival and delayed xenograft rejection in a pig-to-baboon model. The delayed
      xenograft rejection is mediated by both humoral and cellular mechanisms.
      Pretransplantation total lymphoid irradiation combined with cyclosporine A and
      methotrexate can inhibit xenoreactive natural antibody production but not
      elicited antipig antibody production and the xenoreactivity of macrophages.

PMID- 9628678
TI  - Selective convective brain cooling during normothermic cardiopulmonary bypass in
      dogs.
AB  - OBJECTIVE: Although normothermic cardiopulmonary bypass results in improved
      cardiac outcome, patients do not benefit from hypothermia-mediated brain
      protection and thus may be at high risk for ischemic brain injury. The present
      study evaluated the efficacy of selective forced-air cerebral cooling. METHODS:
      Sixteen dogs were anesthetized with either intravenous pentobarbital or inhaled
      halothane (n = 8 for each group). Temperatures were monitored in the esophagus
      (i.e., core), parietal epidural space, and brain parenchyma. Normothermic atrial
      femoral cardiopulmonary bypass and forced-air pericranial cooling (to
      approximately 13 degrees C) were maintained for 150 minutes. Data between groups
      were compared by means of repeated-measures analysis of variance and two-sample t
      test. Within each group, brain-to-core temperature gradients were compared to
      zero by means of the one-sample t test. RESULTS: In pentobarbital-anesthetized
      dogs, after 30 minutes of cerebral cooling, temperatures in the parietal epidural
      space and 1 cm and 2 cm beneath the dura were 3.3 degrees +/- 1.4 degrees C (mean
      +/- standard deviation), 2.6 degrees +/- 1.3 degrees C, and 1.1 degrees +/- 0.6
      degrees C cooler than the core temperature, respectively. At the conclusion of
      the study (i.e., 150 minutes), these temperatures were 4.5 degrees +/- 1.8
      degrees C, 3.9 degrees +/- 1.6 degrees C, and 2.0 degrees +/- 0.9 degrees C
      cooler than the core temperature, respectively. Similar changes were observed in
      halothane-anesthetized dogs. CONCLUSIONS: Regardless of the background
      anesthetic, the magnitude of selective cerebral cooling observed in our study was
      larger than the 1 degree to 2 degrees C changes previously reported to modulate
      ischemic brain injury.

PMID- 9628679
TI  - Improved efficiency of energy transfer to external work in chronic
      cardiomyoplasty based on the pressure-volume relationship.
AB  - OBJECTIVE: Cardiomyoplasty is a surgical procedure to support the failing heart,
      in which a burst-stimulated latissimus dorsi muscle flap is transposed and
      wrapped around the ventricles. The effect of dynamic cardiac compression,
      implemented as cardiomyoplasty, on left ventricular performance remains
      controversial; the mechanism by which clinical symptoms are improved remains
      unclear. To investigate the mechanism for improvement of patients' symptoms, it
      is important to evaluate the effects of cardiomyoplasty on left ventricular
      energetics and on left ventricular systolic and diastolic function. We therefore
      evaluated the efficiency of energy transfer from the native pressure-volume area
      to external work under conditions of 1:3 skeletal muscle burst pacing in an
      animal model with chronic heart failure. METHODS: In seven Merino-Wether sheep,
      cardiomyoplasty was performed after stable heart failure was induced by staged
      coronary embolizations (ejection fraction < 35%). Hemodynamic assessment
      including the assessment of the pressure-volume relationship was performed 8
      weeks after cardiomyoplasty when the latissimus dorsi muscle was fully trained.
      Instantaneous left ventricular pressure and volume were measured with a catheter
      tipped manometer and a conductance catheter during steady-state conditions and
      after a transient inferior vena cava occlusion. The effect of dynamic cardiac
      compression on left ventricular systolic function was assessed by comparing pre
      assisted and assisted beats and on diastolic function by comparing assisted and
      post-assisted beats. RESULT: The slope of the end-systolic pressure-volume
      relationship decreased by 30.5% +/- 27.8% (p = 0.02) during assisted beats.
      However, left ventricular pump performance improved by increasing stroke volume
      and external work by 35.9% +/- 36.0% (p = 0.03) and 9.7% +/- 6.8% (p = 0.03),
      respectively, resulting in a reduction of the volume intercept. As a result, the
      end-systolic pressure-volume relationship shifted to the left. The efficiency of
      energy transfer from the native pressure-volume area to the overall external work
      improved by 7.6% +/- 8.2% (p = 0.04). Cardiomyoplasty did not affect the time
      constant of left ventricular isovolumic pressure decline or the maximal rate of
      pressure decay, which suggested that cardiomyoplasty did not affect left
      ventricular relaxation. CONCLUSIONS: Dynamic cardiac compression in the form of
      cardiomyoplasty enhanced left ventricular pump performance without interrupting
      left ventricular filling. The ratio of energy transfer from the native pressure
      volume area to the overall external work suggests a myocardial oxygen-sparing
      effect of cardiomyoplasty.

PMID- 9628680
TI  - A canine model of dilated cardiomyopathy induced by repetitive intracoronary
      doxorubicin administration.
AB  - OBJECTIVE: A simple and reproducible large animal model of dilated cardiomyopathy
      has yet to be developed. This study was performed to establish a canine model of
      dilated cardiomyopathy. METHODS: Six closed-chest pure-bred beagles weighing 8 to
      12 kg (10 +/- 1.9 kg) underwent intracoronary infusion of doxorubicin
      (Adriamycin). Low-dose (0.7 mg/kg) doxorubicin was infused into the left main
      coronary artery through a 5F Judkins catheter. Infusions were repeated weekly for
      5 weeks. We evaluated the effects on cardiac hemodynamics, chamber size, the
      neuroendocrine system, and cardiac ultrastructure before and 1 and 3 months after
      five intracoronary infusions of doxorubicin. RESULTS: Three months after
      treatment, fractional shortening (mean +/- standard error of the mean) had
      decreased from 36.5% +/- 0.8% to 21.7% +/- 1.4% (p = 0.0003), and left
      ventricular ejection fraction had decreased from 71.0% +/- 3.3% to 36.3% +/- 5.5%
      (p = 0.001). The left ventricular diastolic dimension had increased from 27.8 +/-
      0.9 to 35.5 +/- 0.6 mm (p = 0.003), and the left ventricular end-diastolic volume
      had increased from 27.5 +/- 1.8 to 38.3 +/- 1.9 ml (p = 0.015). Left ventricular
      end-diastolic pressure had increased from 8.5 +/- 0.9 to 14.5 +/- 1.1 mm Hg (p =
      0.01), and the stroke volume had decreased from 16.7 +/- 0.9 to 11.5 +/- 0.4 ml
      (p = 0.001). During the same period, the plasma norepinephrine concentration also
      increased from 114 +/- 27.4 to 423 +/- 88.9 pg/ml (p = 0.024), and plasma atrial
      natriuretic peptide levels increased from 33.8 +/- 7.0 to 76.5 +/- 14.8 pg/ml (p
      = 0.012). Histologic changes such as myofiber atrophy and cytoplasmic
      vacuolation, accompanied with interstitial fibrosis, were found predominantly in
      the left ventricle. CONCLUSION: Repeated intracoronary infusions of doxorubicin
      represent a simple and reliable technique to produce dilated cardiomyopathy in
      the dog. This model can be used to evaluate the effects of new therapies,
      especially surgical treatments such as dynamic cardiomyoplasty and reduction
      ventriculoplasty, on dilated cardiomyopathy.

PMID- 9628681
TI  - Intraoperative closure of muscular ventricular septal defect in a canine model
      and application of the technique in a baby.

PMID- 9628682
TI  - Failure of an implantable left ventricular assist device: a distinctive
      electrocardiographic pattern before malfunction.

PMID- 9628683
TI  - Correction of functional tricuspid insufficiency by means of a limited posterior
      crossed suture annuloplasty.

PMID- 9628684
TI  - Transmyocardial laser revascularization: three sequential autopsy cases.

PMID- 9628685
TI  - Transmyocardial revascularization for cardiac transplantation allograft
      vasculopathy.

PMID- 9628686
TI  - Late autograft and homograft endocarditis after the Ross operation.

PMID- 9628687
TI  - Resident training and minimally invasive cardiac surgery.

PMID- 9628688
TI  - Minimal-access redo aortic valve replacement.

PMID- 9628689
TI  - Regarding the surgical ablation of the sinus node.

PMID- 9628690
TI  - Transmyocardial revascularization: mechanism of action with carbon dioxide and
      holmium-yttrium-aluminum-garnet lasers.

PMID- 9628691
TI  - Minimally invasive coronary artery surgery--a word of caution.

PMID- 9628692
TI  - Air embolism with intraaortic balloon counterpulsation during cardiopulmonary
      bypass.

PMID- 9628693
TI  - A piece of my mind. On being eighty.

PMID- 9628694
TI  - "Teachable moments" provide a means for physicians to lower alcohol abuse.

PMID- 9628695
TI  - JCAHO, NCQA, and AMAP establish council to coordinate health care performance
      measurement. Joint Commission on Accreditation of Healthcare Organizations,
      National Committee for Quality Assurance, American Medical Accreditation Program.

PMID- 9628696
TI  - Guidelines for treating dementia-associated agitation.

PMID- 9628697
TI  - From the Centers for Disease Control and Prevention. Self-reported frequent
      mental distress among adults--United States, 1993-1996.

PMID- 9628698
TI  - From the Centers for Disease Control and Prevention. Varicella-related deaths
      among children--United States, 1997.

PMID- 9628700
TI  - Aerospace medicine.

PMID- 9628701
TI  - Controversies: treatment of acute otitis media.

PMID- 9628702
TI  - Controversies: treatment of acute otitis media.

PMID- 9628703
TI  - Controversies: treatment of acute otitis media.

PMID- 9628704
TI  - Controversies: treatment of acute otitis media.

PMID- 9628705
TI  - Rescreening of cervical Papanicolaou smears using PAPNET.

PMID- 9628706
TI  - Rescreening of cervical Papanicolaou smears using PAPNET.

PMID- 9628707
TI  - Rescreening of cervical Papanicolaou smears using PAPNET.

PMID- 9628708
TI  - Rescreening of cervical Papanicolaou smears using PAPNET.

PMID- 9628709
TI  - Lumbar supports and education for the prevention of low back pain in industry: a
      randomized controlled trial.
AB  - CONTEXT: Low back pain is a frequent and costly health problem. Prevention of low
      back pain is important both for the individual patient and from an economic
      perspective. OBJECTIVE: To assess the efficacy of lumbar supports and education
      in the prevention of low back pain in industry. DESIGN: A randomized controlled
      trial with a factorial design. SETTING: The cargo department of an airline
      company in the Netherlands. PARTICIPANTS: A total of 312 workers were randomized,
      of whom 282 were available for the 6-month follow-up. INTERVENTIONS: Subjects
      were randomly assigned to 4 groups: (1) education (lifting instructions) and
      lumbar support, (2) education, (3) lumbar support, and (4) no intervention.
      Education consisted of 3 group sessions on lifting techniques with a total
      duration of 5 hours. Lumbar supports were recommended to be used during working
      hours for 6 months. MAIN OUTCOME MEASURES: Low back pain incidence and sick leave
      because of back pain during the 6-month intervention period. RESULTS: Compliance
      with wearing the lumbar support at least half the time was 43%. In the 282
      subjects for whom data were available, no statistically significant differences
      in back pain incidence (48 [36%] of 134 with lumbar support vs 51 [34%] of 148
      without, P=.81) or in sick leave because of low back pain (mean, 0.4 days per
      month with lumbar support vs 0.4 days without, P=.52) were found among the
      intervention groups. In a subgroup of subjects with low back pain at baseline,
      lumbar supports reduced the number of days with low back pain per month (median,
      1.2 vs 6.5 days per month; P=.03). CONCLUSIONS: Overall, lumbar supports or
      education did not lead to a reduction in low back pain incidence or sick leave.
      The results of the subgroup analysis need to be confirmed by future research.
      Based on our results, the use of education or lumbar supports cannot be
      recommended in the prevention of low back pain in industry.

PMID- 9628710
TI  - Ambient temperature and mortality from unintentional cocaine overdose.
AB  - CONTEXT: Hot weather taxes cardiovascular function and is associated with
      increased deaths from heart disease. Cocaine can cause hypertension, tachycardia,
      coronary vasospasm, arrhythmias, and increased core temperature. OBJECTIVE: To
      determine the association between mortality from cocaine overdose and hot
      weather. SETTING: New York, NY. DESIGN: Retrospective review of medical examiner
      cases from 1990 through 1995. SUBJECTS: All fatal unintentional cocaine overdoses
      from 1990 through 1992 (n = 1382) and all hyperthermia deaths of cocaine users (n
      = 10) were used to identify a maximum daily temperature threshold above which
      mortality from cocaine intoxication increased. The study population consisted of
      all fatal unintentional cocaine overdoses from 1993 through 1995 (n = 2008) and 4
      contemporaneous comparison groups that included fatal unintentional opiate
      overdoses (n = 793), all other fatal unintentional overdoses (n = 85), and a
      subset of homicides (n = 4638) and fatalities from motor vehicle crashes (n =
      815). MAIN OUTCOME MEASURES: The number of overdose deaths and the proportion of
      homicides and traffic fatalities with a positive cocaine toxicology test result
      on days with a maximum temperature above or below the temperature threshold.
      RESULTS: A threshold temperature of 31.1 degrees C (88 degrees F) was identified,
      above which the mean daily number of fatal cocaine overdoses increased steadily.
      On days with a maximum daily temperature of 31.1 degrees C (88 degrees F) or
      higher ("hot days"), the mean daily number of cocaine overdose deaths was 2.34
      (SD = 1.68), which was 33% higher than the mean on days with a maximum
      temperature of less than 31.1 degrees C (88 degrees F) (mean = 1.76 [SD=1.37]
      (P<.001). In contrast, the mean number of opiate overdose deaths per day was 0.81
      (SD = 0.94) on hot days and 0.71 (SD = 0.86) on other days (P=.28). For other
      drug overdose deaths, the mean number of deaths per day was 0.08 (SD = 0.28) on
      hot days and 0.08 (SD = 0.28) on other days (P=.69). Among homicides, the
      proportion with a positive cocaine toxicology test result was 18.9% on hot days
      and 19.5% on other days (P=.69), and among traffic fatalities, the proportions
      with positive cocaine toxicology test results were 9.5% on hot days and 10.3% on
      other days (P=.91). CONCLUSIONS: High ambient temperature is associated with a
      significant increase in mortality from cocaine overdose. Based on our comparison
      groups, the increase is not explained by changes in cocaine use among the general
      population. Although cocaine use is dangerous on all days, it appears to be even
      more dangerous on hot days.

PMID- 9628711
TI  - Influence of socioeconomic and cultural factors on racial differences in late
      stage presentation of breast cancer.
AB  - CONTEXT: Breast cancer mortality is higher among African American women than
      among white women in the United States, but the reasons for the racial difference
      are not known. OBJECTIVE: To evaluate the influence of socioeconomic and cultural
      factors on the racial difference in breast cancer stage at diagnosis. DESIGN:
      Case-control study of patients diagnosed as having breast cancer at the
      University Medical Center of Eastern Carolina from 1985 through 1992. SETTING:
      The major health care facility for 2 rural counties in eastern North Carolina.
      SUBJECTS: Five hundred forty of 743 patients with newly diagnosed breast cancer
      and 414 control women from the community matched by age, race, and area of
      residence. MAIN OUTCOME MEASURES: Breast cancer stage at diagnosis. RESULTS: Of
      the 540 patients, 94 (17.4%) presented with TNM stage III or IV disease. The
      following demographic and socioeconomic factors were significant predictors of
      advanced stage: being African American (odds ratio [OR], 3.0; 95% confidence
      interval [CI], 1.9-4.7); having low income (OR, 3.7; 95% CI, 2.1-6.5); never
      having been married (OR, 2.9; 95% CI, 1.4-5.9); having no private health
      insurance (OR, 2.5; 95% CI, 1.6-4.0); delaying seeing a physician because of
      money (OR, 1.6; 95% CI, 1.1-2.5); or lacking transportation (OR, 2.0; 95% CI, 1.2
      3.6). Univariate analysis also revealed a large number of cultural beliefs to be
      significant predictors. Examples include the following beliefs: air causes a
      cancer to spread (OR, 2.8; 95% CI, 1.8-4.3); the devil can cause a person to get
      cancer (OR, 2.1; 95% CI, 1.2-3.5); women who have breast surgery are no longer
      attractive to men (OR, 1.9; 95% CI, 1.1-3.5); and chiropractic is an effective
      treatment for breast cancer (OR, 2.4; 95% CI, 1.4-4.4). When the demographic and
      socioeconomic variables were included in a multivariate logistic regression
      model, the OR for late stage among African Americans decreased to 1.8 (95% CI,
      1.1 -3.2) compared with 3.0 (95% CI, 1.9-4.7) for race alone. However, when the
      belief measures were included with the demographic and socioeconomic variables,
      the OR for late stage among African Americans decreased further to 1.2 (95% CI,
      0.6-2.5). CONCLUSIONS: Socioeconomic factors alone were not sufficient to explain
      the dramatic effect of race on breast cancer stage; however, socioeconomic
      variables in conjunction with cultural beliefs and attitudes could largely
      account for the observed effect.

PMID- 9628712
TI  - Privacy and confidentiality in the publication of pedigrees: a survey of
      investigators and biomedical journals.
AB  - CONTEXT: Pedigree diagrams efficiently communicate family information to genetics
      investigators; however, the publication of pedigrees poses a risk to the privacy
      and confidentiality of individuals depicted in the diagrams. Two sets of
      authoritative guidelines have been published to protect the privacy and
      confidentiality of subjects, but the influence of these guidelines on publication
      practices for pedigrees is unknown. OBJECTIVE: To determine the attitudes,
      practices, and experiences of investigators and journals with respect to privacy
      and confidentiality concerns in the publication of pedigrees. DESIGN:
      Investigators who have published pedigrees and editors of 26 biomedical journals
      were surveyed. Journals were reviewed for content in their "information for
      authors" sections and for documentation of informed consent in articles
      containing pedigrees. OUTCOME MEASURES: Practices regarding confidentiality and
      privacy reported by investigators and editors. RESULTS: Of 226 surveys sent to
      investigators, 177 were returned (78% response rate). Sixty-one investigators
      (36%) stated that family members were not informed that their pedigree would be
      published; 131 (78%) do not obtain informed consent specifically for pedigree
      publication and only 12 (28%) of the 43 who obtained consent obtained consent
      from all family members depicted. Thirty-two individuals (19%) reported having
      altered published pedigrees and 14 (45%) of 31 who had altered pedigrees stated
      that alterations were not disclosed to journals. Of the 14 journals that
      responded (54% response rate), only 3 reported written policies for managing
      potentially identifying information. Two journals reported having asked authors
      to alter pedigrees and 3 stated they had permitted alterations. A review of 5
      genetics journals over a 2-year period revealed no documentation of consent for
      pedigree publication. CONCLUSIONS: Current practices in the publication of
      pedigrees do not conform with established recommendations and risk the privacy
      and confidentiality of subjects, often without informed consent. Attempts to
      address this problem through the alteration of data are being used, although this
      practice impairs the integrity of scientific communication.

PMID- 9628713
TI  - Why are physicians not prescribing diuretics more frequently in the management of
      hypertension?
AB  - Diuretics have again been recommended by the Sixth Joint National Committee on
      Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI)
      as one of the first-choice medications in the management of hypertension. This
      recommendation is based on the results of numerous randomized, diuretic-based,
      long-term controlled clinical trials that have demonstrated a reduction in both
      cerebrovascular and cardiovascular morbidity. Despite this and other national
      recommendations, the use of diuretics has steadily decreased over the past 15
      years. Reasons include heavy promotion of other medications and the perception
      that diuretics produce adverse metabolic effects and do not reduce coronary heart
      disease events. Data, however, indicate that (1) changes in glucose and
      cholesterol metabolism are minor, especially with the smaller doses now being
      used; (2) cardiovascular morbidity and mortality have been reduced in
      hypertensive patients, even in those with hyperlipidemia or diabetes, when
      diuretics are used; and (3) concerns about hypokalemia-induced arrhythmias have
      been overstated. While special indications exist for other medications in the
      treatment of hypertension, for example, use of an angiotensin-converting enzyme
      inhibitor (usually in addition to a diuretic) for a patient with heart failure or
      diabetic nephropathy, most patients, including those with hyperlipidemia or
      glucose intolerance, can be effectively treated with a diuretic as initial
      therapy or as part of a combination regimen. Diuretics should be used more not
      less frequently; use of diuretics would reduce the number of resistant
      hypertensive patients.

PMID- 9628714
TI  - Profile of preparticipation cardiovascular screening for high school athletes.
AB  - CONTEXT: Sudden death in young competitive athletes due to unsuspected
      cardiovascular disease has heightened concern and interest in the
      preparticipation screening available to high school athletes in the United
      States. OBJECTIVE: To assess the potential adequacy of the preparticipation
      screening process for detecting or increasing the suspicion of cardiovascular
      abnormalities. DESIGN: Current guidelines and requirements for implementation of
      preparticipation screening from each of the high school jurisdictions in the 50
      states and the District of Columbia were analyzed and compared with the 1996
      American Heart Association (AHA) consensus panel guidelines on screening. OUTCOME
      MEASURES: Items contained on preparticipation screening questionnaires; the
      examiners designated to perform screening. RESULTS: Eight states (16%) have no
      approved history and physical examination questionnaires to guide examiners,
      including 1 state without a formal screening requirement. Of the remaining 43
      states, several items relevant to cardiac-related problems were frequently
      omitted from the questionnaires. Exertional dyspnea or chest pain, prior
      limitation from sports, family history of heart disease, or Marfan syndrome were
      included in 0% to 56% of the state forms. Specific cardiovascular items on
      physical examination were included in forms from only 5% to 37% of states,
      including documentation of a heart murmur, irregular heart rhythm, peripheral
      pulses, or stigmata of Marfan syndrome. Seventeen (40%) of 43 states had history
      and physical questionnaires judged to be most adequate with at least 9 of the 13
      AHA recommendations, whereas 12 states (28%) were least adequate with 4 or less
      of these recommended items. Therefore, a total of 20 (40%) of the 51 states have
      no approved history and physical examination questionnaires, or formal screening
      requirement, or forms that were judged to be inadequate. In addition to
      physicians, 21 states also permit nurses or physician assistants to administer
      examinations, and 11 states specifically provide for practitioners with limited
      cardiovascular training (such as chiropractors). CONCLUSIONS: Preparticipation
      athletic screening for cardiovascular disease with standard history and physical
      examination, as presently employed in US high schools, is highly dependent on the
      state-approved questionnaires, which frequently are abbreviated and may be
      inadequate; is implemented by a variety of health care workers with varying
      levels of expertise; and may be severely limited in its power to detect
      potentially lethal cardiovascular abnormalities. These observations should
      represent an impetus for change and improvement in the preparticipation
      cardiovascular screening process for high school athletes.

PMID- 9628715
TI  - Impact of a children's health insurance program on newly enrolled children.
AB  - CONTEXT: Although there is considerable interest in decreasing the number of US
      children who do not have health insurance, there is little information on the
      effect that health insurance has on children and their families. OBJECTIVE: To
      determine the impact of children's health insurance programs on access to health
      care and on other aspects of the lives of the children and their families.
      DESIGN: A before-after design with a control group. The families of newly
      enrolled children were interviewed by telephone using an identical survey
      instrument at baseline, at 6 months, and at 12 months after enrollment into the
      program. A second group of families of newly enrolled children were interviewed
      12 months after the initial interviews to form a comparison sample. SETTING: The
      29 counties of western Pennsylvania, an area with a population of 4.1 million
      people. SUBJECTS: A total of 887 families of newly enrolled children were
      randomly selected to be interviewed; 88.3% agreed to participate. Of these, 659
      (84%) responded to all 3 interviews. The study population consists of 1031 newly
      enrolled children. The children were further classified into those who were
      continuously enrolled in the programs. The 330 comparison families had 460 newly
      enrolled children. MAIN OUTCOME MEASURES: The following access measures were
      examined: whether the child had a usual source of medical or dental care; the
      number of physician visits, emergency department visits, and dentist visits; and
      whether the child had experienced unmet need, delayed care, or both for 6 types
      of care. Other indicators were restrictions on the child's usual activities and
      the impact of being insured or uninsured on the families. RESULTS: Access to
      health care services after enrollment in the program improved: at 12 months after
      enrollment, 99% of the children had a regular source of medical care, and 85% had
      a regular dentist, up from 89% and 60%, respectively, at baseline. The proportion
      of children reporting any unmet need or delayed care in the past 6 months
      decreased from 57% at baseline to 16% at 12 months. The proportion of children
      seeing a physician increased from 59% to 64%, while the proportion visiting an
      emergency department decreased from 22% to 17%. Since the comparison children
      were similar to the newly enrolled children at enrollment into the insurance
      programs, these findings can be attributed to the program. Restrictions on
      childhood activities because of lack of health insurance were eliminated. Parents
      reported that having health insurance reduced the amount of family stress,
      enabled children to get the care they needed, and eased family burdens.
      CONCLUSIONS: Extending health insurance to uninsured children had a major
      positive impact on children and their families. In western Pennsylvania, health
      insurance did not lead to excessive utilization but to more appropriate
      utilization.

PMID- 9628716
TI  - Lumbar supports for prevention of low back pain in the workplace.

PMID- 9628717
TI  - Cocaine use and death during heat waves.

PMID- 9628718
TI  - Preparticipation screening of athletes.

PMID- 9628719
TI  - Analysis of ritonavir for the treatment of HIV disease in children: abstract and
      commentary.

PMID- 9628720
TI  - Connie Adler, MD: living rural medicine.

PMID- 9628721
TI  - JAMA patient page: low back pain.

PMID- 9628722
TI  - One-third-the-sites transition-state inhibitors for purine nucleoside
      phosphorylase.
AB  - Genetic defects in human purine nucleoside phosphorylase cause T-cell deficiency
      as the major phenotype. It has been proposed that efficient inhibitors of the
      enzyme might intervene in disorders of T-cell function. Compounds with features
      of the transition-state structure of purine nucleoside phosphorylase were
      synthesized and tested as inhibitors. The transition-state structure for purine
      nucleoside phosphorylase is characterized by (1) an elevated pKa at N7 of the
      purine ring for protonation or favorable H-bond interaction with the enzyme and
      (2) oxocarbenium ion formation in the ribosyl ring (Kline, P. C., and Schramm, V.
      L. (1995) Biochemistry 34, 1153-1162). Both features have been incorporated into
      the stable transition-state analogues, (1S)-1-(9-deazahypoxanthin-9-yl)-1,4
      dideoxy-1,4-imino-D-ribitol (immucillin-H) and (1S)-1-(9-deazaguanin-9-yl)-1,4
      dideoxy-1, 4-imino-D-ribitol (immucillin-G). Both inhibitors exhibit slow-onset
      tight-binding inhibition of calf spleen and human erythrocyte purine nucleoside
      phosphorylase. The inhibitors exhibit equilibrium dissociation constants (Ki)
      from 23 to 72 pM and are the most powerful inhibitors reported for the enzyme.
      Complete inhibition of the homotrimeric enzyme occurs at one mole of inhibitor
      per mole of enzymic trimer. Binding of the transition-state inhibitor at one site
      per trimer prevents inhibitor binding at the remaining two sites of the
      homotrimer. A mechanism of sequential catalysis at each subunit, similar to that
      of F1 ATPase, is supported by these results. Slow inhibitor dissociation (e.g.,
      t1/2 of 4.8 h) suggests that these compounds will have favorable pharmacologic
      properties. Interaction of transition-state inhibitors with purine nucleoside
      phosphorylase is different from reactant-state (substrate and product analogue)
      inhibitors of the enzyme which bind equally to all subunits of the homotrimer.

PMID- 9628723
TI  - Linker DNA and H1-dependent reorganization of histone-DNA interactions within the
      nucleosome.
AB  - We have employed a site-directed photochemical cross-linking procedure to
      precisely map interactions between nucleosomal DNA and the C-terminal tail of
      core histone H2A. We find that this tail has the potential to contact multiple
      sites within the nucleosome and that these contacts are dependent upon the
      configuration of the complex. This tail contacts DNA near the dyad axis within
      nucleosome core particles but rearranges to a site near the edge of the
      nucleosomal DNA when linker DNA is present. Moreover, in the presence of linker
      histone H1 the contacts near the edge of the nucleosome but not at the dyad are
      further rearranged. In addition, we present further evidence for the suggestion
      that the binding of linker histone causes a subtle but global change in core
      histone-DNA interactions within the nucleosome [Usachenko, S. I., Gavin, I. M.,
      and Bavykin, S. G. (1996) J. Biol. Chem. 271, 3831-3836].

PMID- 9628724
TI  - Asymmetric linker histone association directs the asymmetric rearrangement of
      core histone interactions in a positioned nucleosome containing a thyroid hormone
      response element.
AB  - We describe histone-DNA cross-linking in a positioned nucleosome containing a
      thyroid hormone response element (TRE) from the Xenopus laevis thyroid hormone
      receptor betaA gene (TRbetaA). Histones H3 and H4 are cross-linked to DNA in the
      nucleosome core within 30 base pairs to either side of the dyad axis. Histone H2A
      cross-links to DNA in the core at the dyad axis, and histones H2A and H2B have
      extensive interactions with DNA 40-80 bp away from the dyad axis. Linker histone
      H5 and the globular domain of Xenopus H1(0) associate asymmetrically with DNA at
      one edge of the TRbetaA nucleosome. Nevertheless, the asymmetric association of
      H5 leads to a significant rearrangement of core histone-DNA contacts at the dyad
      axis of the nucleosome. In the presence of linker histone, cross-linkings of H4
      within 15 bp to one side of the dyad axis, of histone H2A at the dyad axis, and
      of H2A and H2B 40-80 bp to one side of the dyad axis are all reduced. This
      reduction in cross-linking occurs preferentially on the side of the nucleosome to
      which H5 is bound. Our results indicate that core histone contacts within
      mononucleosomes are conformationally dynamic and that linker histone
      incorporation at the edge of the nucleosome can influence core histone-DNA
      interactions in an asymmetric way including contacts at the dyad axis.

PMID- 9628725
TI  - Crystal structure of fragment double-D from human fibrin with two different bound
      ligands.
AB  - Factor XIII-cross-linked fragment D (double-D) from human fibrin was crystallized
      in the presence of two different peptide ligands and the X-ray structure
      determined at 2.3 A. The peptide Gly-Pro-Arg-Pro-amide, which is an analogue of
      the knob exposed by the thrombin-catalyzed removal of fibrinopeptide A, was found
      to reside in the gamma-chain holes, and the peptide Gly-His-Arg-Pro-amide, which
      corresponds to the beta-chain knob, was found in the homologous beta-chain holes.
      The structure shows for the first time that the beta-chain knob does indeed bind
      to a homologous hole on the beta-chain. The gamma- and beta-chain holes are
      structurally very similar, and it is remarkable they are able to distinguish
      between these two peptides that differ by a single amino acid. Additionally, we
      have found that the beta-chain domain, like its gamma-chain counterpart, binds
      calcium.

PMID- 9628726
TI  - Theoretical and experimental analysis of ionization equilibria in ovomucoid third
      domain.
AB  - 2D-NMR experiments were used to determine the pKa values ranging from 8.0 to
      >/=11.1 of seven basic residues in turkey ovomucoid third domain (OMTKY3) and
      were compared to values predicted as described by Antosiewicz et al. [(1996)
      Biochemistry 35, 7819-7833]. Lys 13, 29, and 34 were previously attributed with
      increasing the acidity of numerous acidic residues [Schaller, W., and Robertson,
      A. D. (1995) Biochemistry 34, 4714-4723]. These interactions were expected to
      raise the pKa values of those basic groups; however, the pKa values of Lys 13 and
      34 are less than the model compound values. The pKa values of the other basic
      residues are greater than the model compound values and, unlike the acidic
      residues, all are surprisingly insensitive to salt. While the calculations
      properly predict the direction of most of the pKa shifts and provide valuable
      insight into the possible molecular origins of the interactions that perturb pKa
      values, there is a tendency to overestimate the magnitude of the shifts and their
      salt dependence. Interestingly, the shapes of both the calculated and observed
      transitions are often more complex than expected for a simple titration,
      suggesting that pKa values at many sites are changing during the transition.
      Differences between predicted and experimental pKa values and titration profiles
      for some residues may be due to as yet uncharacterized structural changes at the
      extremes of pH.

PMID- 9628727
TI  - The influence of the regulatory chain amino acids Glu-62 and IIe-12 on the
      heterotropic properties of Escherichia coli aspartate transcarbamoylase.
AB  - In the structure of Escherichia coli aspartate transcarbamoylase with CTP bound
      [Kosman, R. P., Gouaux, J. E., and Lipscomb, W. N. (1993) Proteins, Struct.
      Funct. Genet. 15, 147-177] Lys-6 and Glu-62 form a salt-link between two
      regulatory chains. However, recent X-ray structural studies suggest that side
      chain and backbone interactions existed between Glu-62 and Ile-12. Thus the
      interaction between Glu-62 and Ile-12 may help to establish the correct
      conformation of the nucleotide binding site. The present study of two single-site
      mutant enzymes, Glu-62r-->Ala and Ile-12r-->Ala, was undertaken to investigate
      whether the role of Glu-62 is to maintain the stability of the interface between
      the regulatory chains in the dimer, or interacts with the side chain of Ile-12r
      to define the nucleotide binding site. For both the mutant enzymes, the maximal
      velocity, the aspartate saturation at half the maximal velocity, and Hill
      coefficient were close to wild-type values. The Glu-62r-->Ala enzyme showed
      enhanced regulatory effects with ATP, CTP, and UTP. As a result of this mutation
      the enzyme losses its ability to discriminate between CTP and UTP. For the Ile
      12r-->Ala enzyme, the heterotropic properties were reduced or eliminated. The
      enhanced regulatory effects observed with the Glu-62r-->Ala enzyme do not seem to
      be consistent with the presence of a salt-link between Glu-62r and Lys-6r.
      However, based upon kinetic data of the unique but completely opposite
      heterotropic properties of the two mutant enzymes, it is suggested that the side
      chain interaction between Glu-62r and Ile-12r helps to define the conformation of
      the effector binding pocket. In this study, we report the properties of both the
      Glu-62r-->Ala and Ile-12r-->Ala enzymes and their importance for the heterotropic
      activation and inhibition of aspartate transcarbamoylase.

PMID- 9628728
TI  - Determination of the magnetic axes of cobalt(II) and nickel(II) azurins from 1H
      NMR data: influence of the metal and axial ligands on the origin of magnetic
      anisotropy in blue copper proteins.
AB  - The orientation and the axial, Deltachiax, and rhombic, Deltachirh, components of
      the magnetic susceptibility tensor anisotropy for the cobalt(II) and nickel(II)
      derivatives of azurin from Pseudomonas aeruginosa have been determined from 1H
      NMR data. For both derivatives, the axial geometry of the system determines the
      orientation of the chi-tensor, whose z-axis forms an angle of 18.6 and 20.1
      degrees with the Cu-OGly45 axial bond in the cobalt(II) and nickel(II)
      derivatives, respectively. For protons close to this axis, large negative
      pseudocontact shifts are observed, while those close to the NNS plane of the
      equatorial ligands experience lower and positive pseudocontact shifts for the
      same distance. Dipolar shifts are larger in the cobalt derivative, not only
      because of the larger spin number but also due to its intrinsically higher
      anisotropy. The contact contribution to the hyperfine shifts for the coordinated
      residues has been evaluated and analyzed in terms of unpaired spin delocalization
      mechanisms and geometry considerations. The results are extended to other blue
      copper proteins whose cobalt derivatives have been studied by 1H NMR. The
      electronic structure and its implications in the redox properties of the native
      copper proteins are also commented.

PMID- 9628729
TI  - Interaction of the major epitope region of HIV protein gp41 with membrane model
      systems. A fluorescence spectroscopy study.
AB  - Fluorescence spectroscopy (both steady-state and time-resolved) was used to study
      the fragment 579-601 of gp41 ectodomain (HIV-1), a highly conserved sequence and
      major epitope, regarding (1) structural information, (2) interaction with
      membrane model systems, and (3) location in the phospholipid bilayer. The peptide
      was characterized both in its monomeric (after reduction of the disulfide bond
      between cysteine residues) and in the dimeric forms. The change of the
      fluorescence anisotropy between monomer and dimer was rationalized on the basis
      of energy migration, and a distance between the two tryptophan (Trp) residues of
      approximately 6 A was obtained. Using different fluorescence spectroscopy
      approaches, it was demonstrated that, despite the fact that monomeric gp41
      fragment incorporates in the membrane model systems studied, the dimeric form
      does not interact with these vesicles. A methodology based on the increase of the
      mean fluorescence lifetime averaged by the preexponentials was derived, to obtain
      the partition coefficient of the peptide in the different lipid systems.
      Fluorescence quenching using lipophilic probes and red edge excitation shift
      (REES) were used to study the location of the gp41 fragment in the membrane. It
      was concluded that the Trp residue is located in a shallow position, near the
      interface. The REES results show an uncommonly large wavelength shift (18 nm) for
      the gp41 fragment incorporated in the membrane. Our results are consistent with a
      "two steps" model for the gp41 fusion mechanism similar to the one proposed for
      influenza virus hemagglutinin.

PMID- 9628730
TI  - Insulin signaling in the yeast Saccharomyces cerevisiae. 1. Stimulation of
      glucose metabolism and Snf1 kinase by human insulin.
AB  - Effects of human insulin on glucose metabolism in the yeast Saccharomyces
      cerevisiae were studied in this report. Under two conditions of growth limitation
      (glucose-grown cells during transition to stationary phase or spheroplasts during
      incubation in synthetic glucose medium), human insulin (10 and 1 microM,
      respectively) enhanced glycogen accumulation and glycogen synthase activity by 40
      60% compared to control cells. Glycogen phosphorylase activity was also increased
      under the same conditions, but this stimulation was diminished by 35-45% in
      insulin-treated compared to control cells. Thus, under growth limitation, insulin
      causes glycogen phosphorylase and glycogen synthase to become more sensitive to
      inactivation and activation, respectively. In glucose-induced spheroplasts,
      insulin (1 microM), in addition to glycogen accumulation, led to about 2-fold
      increases of the rates of ethanol production and glucose oxidation compared to
      control cells, and the maximal concentration of hexose 6-phosphate was increased
      by 30-40%. In contrast, glucose transport as well as the levels of the allosteric
      regulators, fructose 2,6-bisphosphate and cAMP, were not altered at all. Snf1
      kinase is assumed to be involved in the regulation of glycogen metabolism in
      yeast, although it does not seem to be modulated directly by the glucose
      concentration. Snf1 kinase activity was elevated 5-10-fold in response to insulin
      both during glucose induction of yeast spheroplasts and during transition to
      stationary phase of glucose-grown cells. We conclude that Saccharomyces
      cerevisiae and insulin-sensitive mammalian cells share some parts of the
      signaling cascades regulating oxidative and nonoxidative glucose metabolism in
      response to glucose and insulin.

PMID- 9628731
TI  - Insulin signaling in the yeast Saccharomyces cerevisiae. 2. Interaction of human
      insulin with a putative binding protein.
AB  - A putative insulin-binding protein (Kd = 0.5 +/- 0.2 microM for human insulin)
      was partially purified from solubilized plasma membranes of Saccharomyces
      cerevisiaeby wheat germ agglutinin and insulin affinity chromatographies. The
      binding affinities of various mutant insulin analogues correlated well with their
      capacities to activate glycogen synthase and SNF1 kinase in glucose-induced yeast
      spheroplasts, the ranking of their relative efficacies in yeast and in isolated
      rat adipocytes being similar. Using a bifunctional cross-linker and two different
      experimental protocols, a 53-kDa polypeptide contained in the insulin-binding
      protein preparation was specifically affinity cross-linked to
      [125I]monoiodo[B26]insulin. The relative rankings of the insulin analogues with
      respect to inhibition of cross-linking and binding to the partially purified
      insulin-binding protein were identical. Incubation of intact yeast spheroplasts
      with [125I]monoiodo[AI4]insulin led to specific and time-dependent association of
      the radiolabeled insulin with the cell surface followed by its internalization
      and degradation. These processes were considerably delayed by low temperature and
      energy depletion of the spheroplasts, suggesting involvement of the ATP-dependent
      endosomal apparatus. These data provide evidence for the existence of a low
      affinity insulin-binding protein in the plasma membrane of Saccharomyces
      cerevisiae.

PMID- 9628732
TI  - Insulin signaling in the yeast Saccharomyces cerevisiae. 3. Induction of protein
      phosphorylation by human insulin.
AB  - A low affinity insulin-binding protein in the plasma membrane of Saccharomyces
      cerevisiae has been identified recently (Muller, G., Rouveyre, N., Upshon, C.,
      Gross, E., and Bandlow, W., preceding paper in this issue). Since the mammalian
      insulin receptor functions as a tyrosine kinase with autophosphorylation
      capacity, kinase studies were performed with the partially purified insulin
      binding protein preparation. Incubation with [gamma-32P]ATP in vitro led to
      phosphorylation of the 53-kDa insulin-binding protein on serine but not on
      tyrosine residues. In addition, a 70-kDa polypeptide, copurified with the insulin
      binding protein preparation, was tyrosine-phosphorylated under the same
      conditions. Phosphorylation of both proteins was enhanced by human insulin. These
      results obtained by immunoprecipitation and immunoblotting using specific anti
      phosphoserine/threonine/tyrosine antibodies were confirmed by phosphoamino acid
      analysis of the individual immunoprecipitated and gel-purified 32P-labeled
      phosphoproteins. During gel filtration, the 53-kDa protein coeluted as a 300-kDa
      complex together with the 70-kDa phosphotyrosine-containing protein and was
      coimmunoprecipitated with the latter using an anti-phosphotyrosine antibody,
      strongly arguing for complex formation between the two proteins. The data
      presented raise the possibility that stimulation of glycogen synthesis by insulin
      in yeast is mediated by a 53-kDa insulin-binding protein and a 70-kDa
      phosphotyrosine-containing protein which are organized in a large plasma membrane
      bound signaling complex. Elucidation of the function and molecular mode of
      interaction of these components in yeast may help to understand metabolic insulin
      signaling in mammalian cells.

PMID- 9628733
TI  - BglF, the sensor of the bgl system and the beta-glucosides permease of
      Escherichia coli: evidence for dimerization and intersubunit phosphotransfer.
AB  - The Escherichia coli BglF protein, also designated EIIbgl, is an enzyme II of the
      phosphoenolpyruvate-dependent phosphotransferase system (PTS) that catalyzes
      transport and phosphorylation of beta-glucosides. In addition, BglF has the
      ability, unusual for an EII, to regulate the activity of a transcriptional
      regulator, BglG, by phosphorylating and dephosphorylating it according to beta
      glucoside availability. Together, BglF and BglG constitute a novel sensory
      system. The membrane-bound sensor, BglF, has two phosphorylation sites: site 1
      accepts a phosphoryl group from HPr and delivers it to site 2; site 2 delivers
      the phosphoryl group either to beta-glucosides or to BglG. Here, we provide
      several lines of evidence for the dimerization of BglF and for the occurrence of
      productive intersubunit phosphotransfer within the BglF dimers. (1) Two inactive
      BglF mutant proteins, one lacking phosphorylation site 1 and the other lacking
      site 2, complement one another to allow beta-glucoside utilization by bglF
      strains. (2) The pairs of mutant proteins complement one another in regulating
      BglG activity as a transcriptional antiterminator in vivo. (3) Only when they are
      present in the same membrane preparation do the mutant protein pairs efficiently
      transfer the phosphoryl group from HPr to beta-glucosides and to BglG in vitro.
      (4) Gentle extraction of cellular proteins followed by SDS-PAGE reveals the
      existence of BglF homodimers. A portion of the phosphorylated form of BglF can
      also be extracted from the membrane as a dimer. Dimerization is mediated by the
      membrane-bound IICbgl domain, as indicated by the dimerization of IICbgl by
      itself and of BglF derivatives that contain this domain. Since dimers persist in
      the presence of a reducing agent, they are apparently not held together by
      disulfide bonds. Rather, BglF dimerization might involve hydrophobic interactions
      between residues in the membrane-spanning domain. In addition, we show that BglF
      dimerization is not modulated by beta-glucosides and is therefore not part of the
      mechanism that diverts the phosphoryl group away from BglG to the transported
      sugar upon addition of beta-glucosides to the growth medium.

PMID- 9628734
TI  - Separation of tubulin subunits under nondenaturing conditions.
AB  - The dissociation and separation of the tubulin alpha- and beta-subunits have been
      achieved by binding alpha-subunits to an immunoadsorbent gel and selectively
      inducing release of free beta-subunits. The immunoadsorbent gel was prepared by
      coupling the monoclonal antibody YL1/2 to Sepharose 4B which specifically
      recognizes the C-terminal end of tyrosinated alpha-subunits. Extensive tubulin
      subunit dissociation and separation occurred in Tris buffer at neutral pH but was
      greatly enhanced at basic pHs (8. 0-8.5). The binding of colchicine to
      heterodimeric tubulin resulted in a marked protection against dissociation. The
      dissociation of tubulin subunits was accompanied by loss of colchicine binding
      capacity, and ability to polymerize into microtubules. As shown by circular
      dichroism, loss of functional properties was not due to extensive denaturation of
      tubulin, as tubulin retained most of its secondary structure. Neither of the
      separated alpha- or beta-subunits was able to bind colchicine, but functional
      tubulin that was able to bind colchicine could be reconstituted from the
      dissociated subunits by changing the buffer to a neutral mixture of Tris and
      Pipes. The yield of reconstitution, as estimated from kinetic measurements of
      colchicine binding capacity, amounted to about 25%. Such a yield can probably be
      improved with minor changes in experimental conditions. The quantitative
      dissociation of tubulin into separated "native" alpha- and beta-subunits should
      provide a powerful tool for further studies on the properties of the individual
      tubulin subunits and the structure-function relationships of the tubulins.

PMID- 9628735
TI  - Resistance to HIV protease inhibitors: a comparison of enzyme inhibition and
      antiviral potency.
AB  - Resistance of HIV-1 to protease inhibitors has been associated with changes at
      residues Val82 and Ile84 of HIV-1 protease (HIV PR). Using both an enzyme assay
      with a peptide substrate and a cell-based infectivity assay, we examined the
      correlation between the inhibition constants for enzyme activity (Ki values) and
      viral replication (IC90 values) for 5 active site mutants and 19 protease
      inhibitors. Four of the five mutations studied (V82F, V82A, I84V, and V82F/I84V)
      had been identified as conferring resistance during in vitro selection using a
      protease inhibitor. The mutant protease genes were expressed in Escherichia coli
      for preparation of enzyme, and inserted into the HXB2 strain of HIV for test of
      antiviral activity. The inhibitors included saquinavir, indinavir, nelfinavir,
      141W94, ritonavir (all in clinical use), and 14 cyclic ureas with a constant core
      structure and varying P2, P2' and P3, P3' groups. The single mutations V82F and
      I84V caused changes with various inhibitors ranging from 0.3- to 86-fold in Ki
      and from 0.1- to 11-fold in IC90. Much larger changes compared to wild type were
      observed for the double mutation V82F/I84V both for Ki (10-2000-fold) and for
      IC90 (0.7-377-fold). However, there were low correlations (r2 = 0.017-0.53)
      between the mutant/wild-type ratio of Ki values (enzyme resistance) and the
      mutant/wild-type ratio of viral IC90 values (antiviral resistance) for each of
      the HIV proteases and the viruses containing the identical enzyme. Assessing
      enzyme resistance by "vitality values", which adjust the Ki values with the
      catalytic efficiencies (kcat/Km), caused no significant improvement in the
      correlation with antiviral resistance. Therefore, our data suggest that
      measurements of enzyme inhibition with mutant proteases may be poorly predictive
      of the antiviral effect in resistant viruses even when mutations are restricted
      to the protease gene.

PMID- 9628736
TI  - Identification of ligand binding sites on integrin alpha4beta1 through chemical
      cross-linking.
AB  - We have used chemical cross-linking to identify sequences in integrin alpha4beta1
      that are involved in its interactions with ligands. A recently described leucine
      aspartic acid-valine (LDV)-based small molecule inhibitor of alpha4beta1 (BIO
      1494), that contained a single reactive amino group for targeting the cross
      linking, was used for these studies. The specificity of the interaction was
      defined by (i) the ability to block the interaction with a competitive inhibitor
      lacking the reactive group, (ii) the absolute requirement of divalent cations for
      cross-linking, and (iii) the lack of cross-linking to the functionally related
      integrin alpha4beta7. With ANB-NOS as the cross-linker, only the beta1 chain was
      labeled with BIO-1494, while with the more flexible cross-linker DSS both the
      alpha4 and beta1 chains were modified. Similar results were obtained when cross
      linking was performed on K562 cells expressing alpha4beta1 but not on K562 cells
      expressing alpha2beta1. The site of cross-linking on the beta1 chain was
      localized by CNBr peptide mapping within residues 130-146, a region that contains
      the putative metal binding site DXSXS and for which analogous data had been
      generated with RGD binding to integrin alphaIIbbeta3. The striking similarity
      between the data we generated for an LDV ligand and published data for the RGD
      family supports the notion of a common ligand binding pocket formed by both
      integrin chains. The cross-linking strategy developed here should serve as a
      useful tool for studying alpha4beta1 function.

PMID- 9628737
TI  - Overproduction and characterization of a dimeric non-zinc glyoxalase I from
      Escherichia coli: evidence for optimal activation by nickel ions.
AB  - The ubiquitous glyoxalase system converts toxic alpha-keto aldehydes into their
      corresponding nontoxic 2-hydroxycarboxylic acids, utilizing glutathione (GSH) as
      a cofactor. The first enzyme in this system, glyoxalase I (GlxI), catalyzes the
      isomerization of the hemithioacetal formed nonenzymatically between GSH and
      cytotoxic alpha-keto aldehydes. To study the Escherichia coli GlxI enzyme, the
      DNA encoding this protein, gloA, was isolated and incorporated into the plasmid
      pTTQ18. Nucleotide sequencing of the gloA gene predicted a polypeptide of 135
      amino acids and Mr of 14 919. The gloA gene has been overexpressed in E. coli and
      shown to encode for GlxI. An effective two-step purification protocol was
      developed, yielding 150-200 mg of homogeneous protein per liter of culture.
      Electrospray mass spectrometry confirmed the monomeric weight of the purified
      protein, while gel filtration analysis indicated GlxI to be a homodimer of 30
      kDa. Zinc, the natural metal ion found in the Homo sapiens and Saccharomyces
      cerevisiae GlxI, had no effect on the activity of E. coli GlxI. In contrast, the
      addition of NiCl2 to the growth medium or to purified E. coli apo-GlxI greatly
      enhanced the enzymatic activity. Inductively coupled plasma and atomic absorption
      analyses indicated binding of only one nickel ion per dimeric enzyme, suggesting
      only one functional active site in this homodimeric enzyme. In addition, the
      apoprotein regained maximal activity with one molar equivalence of nickel
      chloride, indicative of tight metal binding. The effects of pH on the kinetics of
      the nickel-activated enzyme were also studied. This is the first example of a non
      zinc activated GlxI whose maximal activation is seen with Ni2+.

PMID- 9628739
TI  - Evaluation of the kinetic mechanism of Escherichia coli glycinamide
      ribonucleotide transformylase.
AB  - A kinetic scheme is presented for Escherichia coli glycinamide ribonucleotide
      transformylase (GAR transformylase, EC 2.1.2.2) based on a steady-state and pre
      steady-state kinetic analysis of the reaction in both directions employing
      stopped-flow absorbance and fluorescence spectroscopy. Steady-state parameters
      showed that kcat for the reverse direction is about 10 times lower than that for
      the forward direction although the Km values for formyl dideazafolate and
      dideazafolate or for glycinamide ribonucleotide and formyl glycinamide
      ribonucleotide are similar. No pre-steady-state transient was observed in either
      direction, and the single-turnover rate constant under saturating levels of
      substrates in each direction was found to be very close to the respective steady
      state kcat value. This indicates that steps involving ternary complexes are rate
      determining for steady-state turnover in each direction. By conducting the single
      turnover reactions under various preincubation and mixing conditions, a random
      sequential kinetic mechanism was implicated in which the enzyme binds glycinamide
      ribonucleotide or formyl dideazafolate productively in no obligatory order. The
      collective data provided a quantitative kinetic scheme to serve as a basis for
      the analysis of mutations.

PMID- 9628738
TI  - Structure elucidation of sphingolipids from the mycopathogen Paracoccidioides
      brasiliensis: an immunodominant beta-galactofuranose residue is carried by a
      novel glycosylinositol phosphorylceramide antigen.
AB  - Two major acidic glycolipid components (Pb-1 and Pb-2) have been extracted from
      the mycopathogen Paracoccidioides brasiliensis, a thermally dimorphic fungus
      endemic to rural areas of South and Central America. Sera of all patients
      exhibiting paracoccidioidomycosis were found to be reactive with Pb-1, but not
      with Pb-2; no reactivity was observed with sera of healthy patients or those with
      histoplasmosis [Toledo, M. S., Suzuki, S., Straus, A. H., and Takahashi, H. K.
      (1995) J. Med. Vet. Mycol. 33, 247-251]. We report here the complete structure
      elucidation of both P. brasiliensis glycolipids using monosaccharide, fatty acid,
      sphingosine, and inositol component analysis by GC-MS; 1H- and 31P NMR
      spectroscopy; ESI-MS and -MS/CID-MS, linkage analysis, and exoglycosidase
      digestion. The compounds were found to be glycosylinositol phosphorylceramides
      (GIPCs) with the following structures: Pb-2, Manpalpha1-->3Manpalpha1-->2Ins1-P
      1Cer; and Pb-1, Manpalpha1-->3[Galfbeta1-->6]Manpalpha1-->2Ins1- P-1Cer. The
      serologically nonreactive Pb-2 appears to be a biosynthetic intermediate between
      mannosylinositol phosphorylceramide (MIPC), which is widely distributed among
      fungi, and the antigenic Pb-1. Pb-1 is a novel glycosphingolipid, similar to a
      triglycosyl IPC (Hc-VI) reported from Histoplasma capsulatum [Barr, K., Laine,
      R.A, and Lester, R. L. (1984) Biochemistry 23, 5589-5596], but differing in the
      anomeric configuration of the terminal Galf1-->6 residue, which is
      immunodominant. The significance of these structures as serological and taxonomic
      markers, as well as their potential utility as targets for immunodiagnostic
      agents, is discussed.

PMID- 9628740
TI  - The catalytic mechanism of kynureninase from Pseudomonas fluorescens: evidence
      for transient quinonoid and ketimine intermediates from rapid-scanning stopped
      flow spectrophotometry.
AB  - The reaction of Pseudomonas fluorescens kynureninase with L-kynurenine and L
      alanine has been examined using rapid-scanning stopped-flow spectrophotometry.
      Mixing kynureninase with 0.5 mM L-kynurenine results in formation of a quinonoid
      intermediate, with lambdamax = 494 nm, within the dead time (ca. 2 ms) of the
      stopped-flow mixer. This intermediate then decays rapidly, with k = 743 s-1, and
      this rate constant is reduced to 347 s-1 in [2H]H2O, suggesting that protonation
      of this intermediate by a solvent exchangeable proton takes place. Rapid quench
      experiments demonstrate that covalent changes in the cofactor occur, as pyridoxal
      5'-phosphate is converted to pyridoxamine 5'-phosphate in about 30 mol % within 5
      ms after mixing. Under single turnover conditions in the reaction of kynureninase
      with l-kynurenine, a transient shoulder absorbing at 335 nm is observed that may
      be a pyruvate ketimine intermediate. In contrast, the reaction of kynureninase
      with 0.5 mM l-kynurenine in the presence of 10 mM benzaldehyde results in the
      formation of a quinonoid intermediate (k = 67.4 s-1) with a very strong
      absorbance peak at 496 nm. The reaction of L-alanine with kynureninase exhibits
      the rapid formation (386 s-1 at 0.1 M) of an external aldimine intermediate
      absorbing at 420 nm, followed by slower formation of a quinonoid intermediate
      with a peak at 500 nm (k = 2.5 s-1). The 420 nm peak then decays slowly with
      concomitant formation of a peak at 320 nm corresponding to a pyruvate ketimine.
      These data demonstrate that quinonoid and ketimine intermediates are
      catalytically competent in the reaction mechanism of kynureninase, and provide
      additional support for our proposed mechanism for kynureninase from steady-state
      kinetic studies [Koushik, S. V., Sundararaju, B., and Phillips, R. S.
      Biochemistry 1998, 37, 1376-1382].

PMID- 9628741
TI  - Oxygen reactivity of an NADH oxidase C42S mutant: evidence for a C(4a)
      peroxyflavin intermediate and a rate-limiting conformational change.
AB  - The flavoprotein NADH oxidase (O2 --> 2H2O) from Enterococcus faecalis 10C1
      contains a cysteinyl redox center, in addition to FAD. We have proposed a
      cysteine-sulfenic acid (Cys-SOH) structure for the oxidized form of Cys42; the
      presence of this redox center is consistent with the stoichiometries reported for
      earlier reductive titrations of wild-type oxidase, and we have proposed that
      Cys42-SH plays a key role in the overall four-electron reduction of O2 --> 2H2O.
      To test these proposals, we provide in this report an analysis of the oxidative
      half-reaction of an oxidase mutant in which Cys42 is replaced by Ser. NADH
      titrations lead to direct flavin reduction with 1.05 equiv of NADH/FAD and give
      rise to the formation of a very stable E-FADH2.NAD+ complex. Kinetic analyses
      indicate that this species is catalytically competent, and its reactivity with O2
      has been analyzed in detail by stopped-flow spectrophotometry using both single
      wavelength and diode-array modes of data acquisition. The combined results of
      this analysis demonstrate that replacement of Cys42 with Ser provides for an
      altered O2 reduction stoichiometry in which H2O2, not 2H2O, is the product. The
      two subunits of the reduced enzyme.NAD+ complex react with O2 in an asymmetric
      mechanism, consistent with an alternating sites cooperativity model such as that
      proposed [Miller, S. M., Massey, V., Williams, C. H., Jr., Ballou, D. P., and
      Walsh, C. T. (1991) Biochemistry 30, 2600-2612] for mercuric reductase. An FAD
      C(4a)-hydroperoxide is identified as the primary oxygenated intermediate in
      reoxidation of the complex, but the reaction of O2 with the complementary subunit
      does not proceed until full reoxidation has occurred at the primary subunit. To
      our knowledge, this is the first report of a C(4a)-peroxyflavin intermediate
      outside the flavoprotein monooxygenase class.

PMID- 9628742
TI  - Mutagenic specificity of model estrogen-DNA adducts in mammalian cells.
AB  - Site-specifically modified oligodeoxynucleotides were used to explore the
      mutagenic properties of the model estrogen-DNA adducts N2-[3-methoxyestra
      1,3,5(10)-trien-6(alpha, beta)-yl]-2'-deoxyguanosine (dG-N2-3MeE) and N6-[3
      methoxyestra-1,3, 5(10)-trien-6(alpha,beta)-yl]-2'-deoxyadenosine (dA-N6-3MeE) in
      simian kidney (COS-7) cells. Oligodeoxynucleotides (5'TCCTCCTCXCCTCTC; X = dG,
      dA, dG-N2-3MeE, or dA-N6-3MeE) containing an unmodified or model estrogen lesion
      were inserted into single-stranded (ss) phagemid vectors. These ss vectors were
      transfected into COS-7 cells. The progeny plasmid obtained were used to transform
      Escherichia coli DH10B. The transformants were analyzed by oligodeoxynucleotide
      hybridization and sequencing to determine the mutation frequency and spectrum.
      Preferential incorporation of dCMP, the correct base, was observed opposite the
      dG-N2-3MeE lesion. Targeted mutations showing G --> T transversions were
      detected, along with a small number of G --> C transversions. When a dA-N6-3MeE
      modified oligodeoxynucleotide was used, preferential incorporation of dTMP, the
      correct base, was also observed. Targeted mutations representing A --> T
      transversions were detected, accompanied by a small amount of A --> G
      transitions. The frequency of mutation observed opposite dA-N6-3MeE (17.5%) was
      2.3 times higher than that observed opposite dG-N2-3MeE (7.5%). These results
      indicate that estrogen DNA adducts have mutagenic potential in mammalian cells.

PMID- 9628743
TI  - Human replication protein A preferentially binds cisplatin-damaged duplex DNA in
      vitro.
AB  - Fractionation of human cell extracts by cisplatin-DNA affinity chromatography was
      employed to identify proteins capable of binding cisplatin-damaged DNA. A
      specific protein-DNA complex, termed DRP-3, was identified in an electrophoretic
      mobility shift assay (EMSA) using a cisplatin-damaged DNA probe. Using this assay
      we purified DRP-3 and the final fraction contained proteins of 70, 53, 46, 32,
      and 14 kDa. On the basis of subunit molecular weights, antibody reactivity, and
      DNA binding activities, DRP-3 was identified as human replication protein A
      (hRPA). Therefore, we assessed the binding of recombinant human RPA (rhRPA) to
      duplex cisplatin-damaged DNA in vitro. Global treatment of a highly purified
      completely duplex 44-bp DNA with cisplatin resulted in a 10-20-fold increase in
      rhRPA binding compared to the undamaged control. The stability of the RPA-DNA
      complexes was assessed, and NaCl and MgCl2 concentrations that completely
      inhibited rhRPA binding to undamaged DNA had only a minimal effect on binding to
      duplex platinated DNA. We assessed rhRPA binding to a duplex DNA containing a
      single site-specific 1,2-d(GpG) cisplatin adduct, and the results revealed a 4-6
      fold increase in binding to this DNA substrate compared to an undamaged control
      DNA of identical sequence. These results are consistent with RPA being involved
      in the initial recognition of cisplatin-damaged DNA, possibly mediating DNA
      repair events. Therefore, we assessed how another cisplatin DNA binding protein,
      HMG-1, affected the ability of rhRPA to bind damaged DNA. Competition binding
      assays show minimal dissociation of either protein from cisplatin-damaged DNA
      during the course of the reaction. Simultaneous addition experiments revealed
      that HMG-1 binding to cisplatin-damaged DNA was minimally affected by rhRPA,
      while HMG-1 inhibited the damaged-DNA binding activity of rhRPA. These data are
      consistent with HMG-1 blocking DNA repair and possibly having the capability to
      enhance the cytotoxic efficacy of the drug cisplatin.

PMID- 9628744
TI  - Kinetic and spectroscopic properties of the YZ* radical in Ca2+- and Cl--depleted
      photosystem II preparations 

PMID- 9628745
TI  - Induction of relational schemas: common processes in reasoning and complex
      learning.
AB  - Five experiments were performed to test whether participants induced a coherent
      representation of the structure of a task, called a relational schema, from
      specific instances. Properties of a relational schema include: An explicit symbol
      for a relation, a binding that preserves the truth of a relation, potential for
      higher-order relations, omnidirectional access, potential for transfer between
      isomorphs, and ability to predict unseen items in isomorphic problems. However
      relational schemas are not necessarily coded in abstract form. Predictions from
      relational schema theory were contrasted with predictions from configural
      learning and other nonstructural theories in five experiments in which
      participants were taught a structure comprised of a set of initial-state,operator
      ->end-state instances. The initial-state,operator pairs were presented and
      participants had to predict the correct end-state. Induction of a relational
      schema was achieved efficiently by adult participants as indicated by ability to
      predict items of a new isomorphic problem. The relational schemas induced showed
      the omnidirectional access property, there was efficient transfer to isomorphs,
      and structural coherence had a powerful effect on learning. The "learning to
      learn" effect traditionally associated with the learning set literature was
      observed, and the long-standing enigma of learning set acquisition is explained
      by a model composed of relational schema induction and structure mapping.
      Performance was better after reversal of operators than after shift to an
      alternate structure, even though the latter entailed more overlap with previously
      learned tasks in terms of the number of configural associations that were
      preserved. An explanation for the reversal shift phenomenon in terms of induction
      and mapping of a relational schema is proposed. The five experiments provided
      evidence supporting predictions from relational schema theory, and no evidence
      was found for configural or nonstructural learning theories.

PMID- 9628746
TI  - Verification of statements about story worlds that deviate from normal
      conceptions of time: what is true about Einstein's Dreams?
AB  - College students read chapters from a novel written by Alan Lightman (Einstein's
      Dreams) and later provided verification judgments on the truth/falsity of test
      statements. Each chapter described a different fictional village that
      incorporated assumptions about time that deviate from our normal TIME schema,
      e.g., citizens knowing exactly when the world will end, time flowing backward
      instead of forward. These novel assumptions about time provided interesting
      insights about life and reality. In two experiments, we examined whether readers
      could accurately incorporate these novel assumptions about time in the fictional
      story worlds, as manifested in the verification judgments for statements after
      story comprehension. The test statements included verbatim typical, verbatim
      atypical, inference typical, and inference atypical information from the
      perspective of mundane reality that meshes with a normal TIME schema.
      Verification ratings were collected on a 6-point scale in Experiment 1, whereas
      Experiment 2 used a signal-response technique in which binary true/false
      decisions were extracted at-.5, 1.5, 3.5, 5.5, and 10.0 s. The college students
      were measured on literary expertise, reading skill, working memory span, and
      reading time. Readers with comparatively high literary expertise showed truth
      discrimination scores that were compatible with a schema copy plus tag model,
      which assumes that readers are good at detecting and remembering atypical
      verbatim information; this model predicts better (and faster) truth
      discrimination for verbatim atypical statements than for verbatim typical
      statements. In contrast, fast readers with comparatively low literary expertise
      were compatible with a filtering model; this model predicts that readers gloss
      over (or suppress) atypical verbatim information and show advantages for verbatim
      typical information. All groups of readers had trouble inferentially propagating
      the novel assumptions about time in a fictional story world, but the slower
      readers were more accurate in their verification of the atypical inferences. A
      construction-integration model could explain the interactions among literary
      expertise, reading time, and the typicality of test statements.

PMID- 9628747
TI  - An AI approach to dynamic visual field testing.
AB  - Visual field test results are crucial to the accuracy and efficiency of
      diagnosing blinding diseases such as glaucoma. Herein, a method of integrating
      self-organizing neural networks and empirical heuristics is used to perform
      visual field tests via a dynamic test strategy, which can lead to a reduction in
      the number of trials in a perimetric test. Experiments performed using clinical
      test records show that we are able to reduce by 20% to 30% the number of trials
      per test without much adverse effect on the accuracy of the tests.

PMID- 9628748
TI  - An efficient procedure for permutation tests in imaging research.
AB  - Recent interest in hypothesis testing on functional imaging data has spurred the
      development of several statistical techniques. The purpose of this paper is to
      provide a method to reduce the computational intensity associated with
      randomization tests of positron emission tomography imaging data. We discuss the
      advantages and disadvantages of traditional distributional hypothesis testing
      versus the advantages and disadvantages of randomization tests. A method for
      reducing the computational intensity of randomization uses a conjunction of
      updating and sequenching and results in significantly reduced processing. The
      running times of randomization methods are compared.

PMID- 9628749
TI  - Tools for immunization guideline knowledge maintenance. I. Automated generation
      of the logic "kernel" for immunization forecasting.
AB  - IMM/Def is a prototype computer program designed to facilitate the building and
      maintenance of a rule-based program which performs childhood immunization
      forecasting. An immunization forecasting program takes as input a child's
      immunization history and produces recommendations as to which vaccinations are
      due and which should be scheduled next. A significant amount of the knowledge
      required for immunization forecasting can be expressed in tabular form, including
      the parameters that indicate the minimum age when each dose may be given and the
      minimum intervals between doses. The choice of which of these sets of parameters
      apply to a particular case depends upon additional clinical logic. To perform
      forecasting, this logic must be applied in three temporal contexts: (1) a dose is
      due now, (2) a dose is not yet due, and (3) a dose must be scheduled to follow a
      dose which is due now. Building and maintaining this logic by hand is a
      formidable challenge. IMM/Def demonstrates how this task can be simplified by
      first defining immunization "definition logic" which can be automatically
      translated into if-then rules for each of the three contexts. The approach has
      been applied successfully to the six childhood vaccination series which are
      routinely administered. A key advantage is that IMM/Def allows one to have two
      specifications of the logic that can be examined independently and that can be
      cross-checked to help assure completeness, consistency, and accuracy of the
      logic. The paper describes how IMM/Def performs its translation and discusses
      several design issues and lessons learned.

PMID- 9628750
TI  - Tools for immunization guideline knowledge maintenance. II. Automated Web-based
      generation of user-customized test cases.
AB  - IMM/Test is a prototype software tool built to generate test cases that can be
      used to help test and verify the internal logic of an immunization forecasting
      program. A forecasting program takes as input a child's immunization history and
      produces recommendations as to which vaccinations are due and which should be
      scheduled next. IMM/Test was developed to test a specific immunization
      forecasting program, IMM/Serve. In addition, IMM/Test has been incorporated into
      a broader Web-based tool, IMM/Web, which allows the user (e.g., a member of an
      immunization registry staff) to customize the parameters used for immunization
      forecasting (e.g., the minimum ages for each dose and the minimum wait intervals
      between doses) to reflect local practice. IMM/Web then generates a customized set
      of test cases that may be used to test the user's immunization forecasting
      program. The user may also request that the test cases be automatically passed to
      IMM/Serve to analyze using the newly defined parameters. The paper describes the
      internal design of IMM/Test and IMM/Web and discusses certain lessons learned in
      the implementation of the two programs.

PMID- 9628751
TI  - Joint time and time-frequency optimal detection of K-complexes in sleep EEG.
AB  - Automated detection of waveforms such as delta and K-complex in the EEG is an
      important component of sleep stage monitoring. The K-complex is a key feature
      that contributes to sleep stages assessment. However, its automated detection is
      still difficult due to the stochastic nature of the EEG. In this paper, we
      propose a detection structure which can be interpreted as joint linear filtering
      operations in time and time-frequency domains. We also introduce a method of
      obtaining the optimum detector from training data, and we show that the resulting
      receiver offers better performances than the one obtained via the Fisher
      criterion maximization. The efficiency of this approach for K-complexes detector
      design is explored. It results from this study that the obtained receiver is
      potentially the best one which can be found in the literature. Finally, it is
      emphasized that this methodology can be advantageously used to solve many other
      detection problems.

PMID- 9628752
TI  - Primary culture of adult mouse olfactory receptor neurons.
AB  - Olfactory receptor neurons (ORNs) are unique because they can be replaced by stem
      cells throughout life. Previous studies have demonstrated that adult mouse
      olfactory epithelium (OE) injured by exposure to ZnSO4 through nasal irrigation
      can stimulate stem cell mitotic activity in situ, which continues when placed in
      culture. We report on an improved ZnSO4 delivery method, mist inhalation, which
      produces more consistent and greater yields of OE cells. Cultures established
      following this method contained bipolar, nest, fusiform, and giant cells. The
      bipolar cells usually underwent asymmetric process development. Some bipolar
      cells reacted positively to neuron-specific antibodies and were immunonegative
      for keratin and glia-specific proteins, suggesting that they were ORNs. Those
      that were negative for the neuron-specific proteins may represent either neuron
      progenitors or olfactory ensheathing cells. The fusiform cells were relatively
      small and undifferentiated, exposure to brain-derived neurotrophic factor
      resulted in their decrease and an increase in bipolar cells. Therefore, they
      might be the stem cells. The nest cells had morphological characteristics of
      epithelia and bound keratin antibodies. The giant cells had the morphology of
      epithelial cells but were negative for keratin; they may represent a unique cell
      population induced by the ZnSO4. These results indicate that the major cell types
      of intact OE are present in our cultures, and each retains characteristics found
      in situ. The mist inhalation method provides an in vitro population of adult
      mitotically active neurons for study.

PMID- 9628753
TI  - Expression of brain-derived neurotrophic factor and its cognate receptor, TrkB,
      in the rat suprachiasmatic nucleus.
AB  - Photic entrainment of mammalian circadian rhythms occurs because the pacemaker in
      the suprachiasmatic nuclei (SCN) of the hypothalamus is endowed with a rhythmic
      sensitivity to photic signals conveyed by the retinohypothalamic tract. Since
      brain-derived neurotrophic factor (BDNF) has been implicated in the functional
      modulation of other retinal targets, the rat SCN was examined for expression and
      cellular distribution of this neurotrophin and TrkB, the tyrosine kinase receptor
      that preferentially binds BDNF. The rat SCN was found to express the mature BDNF
      peptide and mRNA by Western blotting, enzyme-linked immunosorbent assay (ELISA),
      and reverse transcription-polymerase chain reaction (RT-PCR) analyses. BDNF
      immunoreactivity and hybridization signal for its mRNA were coextensively
      localized within a number of SCN cells throughout the rostrocaudal axis of each
      nucleus. In addition, some cells intercalated within the optic chiasm were
      distinguished by expression of BDNF immunoreactivity or mRNA. Immunostaining for
      the TrkB receptor was also evident in the SCN within terminals or fibers
      predominantly located along the SCN/optic chiasm interface and within scattered
      perikarya near the medial border of each nucleus. Combined in situ hybridization
      and immunocytochemical analysis revealed that BDNF mRNA-expressing cells within
      the ventrolateral SCN were often closely apposed to TrkB-positive fibers
      extending from the optic chiasm. These findings raise the possibility that target
      derived interactions between BDNF and TrkB receptors could play a role in the
      circadian modulation of SCN pacemaker sensitivity to photic input transmitted by
      the retinohypothalamic tract.

PMID- 9628754
TI  - Fast and sensitive method for simultaneous measurement of cell proliferation rate
      and drug sensitivity in rat cerebral cortex.
AB  - A proliferation assay based on the production of mini-units of tissue was adopted
      and modified for the simultaneous determination of cell proliferation rate and
      the effect of genistein in rat cerebral cortex. Mini-units of tissue were
      produced from rat cerebral cortex immediately after killing the animal and
      incubated with culture medium containing 3H-methyl-thymidine during 90 min. The
      proliferation rate was assessed by measurement of 3H-methyl-thymidine
      incorporation into trichloroacetic acid insoluble material/mg of protein/min. The
      mini-unit method preserves the neural-cell topological relation existing in vivo
      and, in addition, has several additional advantages: (1) the short incubation
      time required limits the metabolic changes, (2) the sensitivity to drugs can be
      assessed simultaneously with the cell proliferation rate, (3) the complete
      procedure can be performed within 4-6 h, and (4) many experiments can be
      performed with the tissue from one animal. Genistein in doses from 10 to 100
      microM inhibited cell proliferation in a concentration-dependent manner. The
      percentage of inhibition was highest in young animals and decreased with
      increasing age. This method is a powerful tool for the study of drugs with short
      time onset mechanisms of action and can be useful for the screening of new drugs.

PMID- 9628755
TI  - Intrastriatal transplantation of rat adrenal chromaffin cells seeded on
      microcarrier beads promote long-term functional recovery in hemiparkinsonian
      rats.
AB  - Possible biologic treatments for Parkinson's disease, a disorder caused by the
      deterioration of dopaminergic neurons bridging the nigrostriatal system, have
      recently focused on fetal cell transplantation. Because of ethical and tissue
      availability issues concerning fetal cell transplantation, alternative cell
      sources are being developed. The adrenal medulla has been used as a cell
      transplant source because of the capacity of the cells to provide catecholamines
      and to transform into a neuronal phenotype. However, adrenal tissue transplants
      have shown limited success, primarily because of their lack of long-term
      viability. Recently, seeding adrenal chromaffin cells on microcarrier beads has
      been shown to enhance the cell viability following neural transplantation. In the
      present study, we further investigated whether transplantation of rat adrenal
      chromaffin cells seeded on microcarrier beads into the striatum of 6
      hydroxydopamine-induced hemiparkinsonian rats would result in a sustained
      functional recovery. Behavioral tests using the apomorphine-induced rotational
      and elevated body swing tests up to 12 months posttransplantation revealed a
      significant behavioral recovery in animals that received adrenal chromaffin cells
      seeded on microcarrier beads compared to animals that received adrenal chromaffin
      cells alone, medium alone, or beads alone. Histological examination of tissue at
      14 months posttransplantation revealed evidence of tyrosine hydroxylase-positive
      cells and an on-going glial response in animals transplanted with adrenal
      chromaffin cells seeded on microcarrier beads, in contrast to absence of such
      immunoreactive responses in the other groups. These findings support a
      facilitator role for microcarrier beads in transplantation of adrenal chromaffin
      cells or other cells that are easily rejected by the CNS.

PMID- 9628756
TI  - Therapeutic effects of aldose reductase inhibitor on experimental diabetic
      neuropathy through synthesis/secretion of nerve growth factor.
AB  - We investigated alterations in nerve growth factor (NGF) and ciliary neurotrophic
      factor (CNTF) contents during treatment with epalrestat, an aldose reductase
      inhibitor (ARI), on streptozotocin (STZ)-induced diabetic neuropathy in rats.
      Diabetic rats showed a statistically significant reduction in H-wave-related
      sensory nerve conduction velocity (HSNCV) and in NGF content in sciatic nerves
      during the experiment of 8 weeks. No reduction in the CNTF content in sciatic
      nerves was seen in the diabetic rats. The epalrestat treatment, which started 4
      weeks after STZ injection, resulted in a significantly greater NGF content and
      faster HSNCV than those in untreated diabetic rats. But no statistically
      significant alterations of motor nerve conduction velocity (MNCV) or CNTF content
      were seen during the treatment. ARI showed the stimulating effect for NGF
      synthesis/secretion in rat Schwann cell culture in vitro. These findings suggest
      that decreased levels of NGF in diabetic sciatic nerves may be involved in the
      pathogenesis of diabetic neuropathy in these rats and further show that
      epalrestat treatment can be useful for the treatment of diabetic neuropathy
      through NGF-induction in Schwann cells and/or inhibition of the polyol pathway.

PMID- 9628757
TI  - Degeneration of the dendritic arbor as an index of neurotoxicity in identified
      catecholamine neurons in rat brain slices.
AB  - Although catecholamine neurons are vulnerable targets for neurotoxins and
      degenerative disease, few in vitro studies have investigated the mechanisms of
      neurodegeneration in these cells. We therefore developed a brain slice
      preparation for this purpose. Rats were killed by cervical dislocation and 400
      microm-thick horizontal slices containing midbrain catecholamine neurons were
      incubated for 2 h in the presence or absence of kainic acid (KA, 50 microM).
      After fixation, the slices were recut by a technique that provided thin (40
      microm) sections in the same plane as the parent slice. Catecholamine neurons in
      these coplanar sections were labeled by immunostaining for tyrosine hydroxylase
      (TH) coupled with diaminobenzidine. The topographical organization of the
      horizontal plane of the brain was retained in the coplanar sections, enabling
      precise identification of catecholamine neurons in the thin sections, by
      reference to an atlas in the horizontal plane. In this study we examined neurons
      in the substantia nigra (SN). A key feature of the immunostaining was that it
      revealed both the cell body and also the extensive dendritic projections of SN
      neurons in the horizontal plane. After treatment with KA, cell bodies remained
      intact but the dendrites were truncated or fragmented. The loss of dendrites is a
      sensitive and readily quantifiable indicator of damage. KA caused significant
      reductions in the proportion of SN neurons with intact dendrites and in the total
      length of the dendrites, measured using a computer program. The sensitive index
      of damage and the facility to clearly distinguish catecholamine groups that are
      topographically close yet functionally distinct are the principal features of the
      experimental approach that we have developed. The preparation offers major
      advantages for investigating the selective vulnerability or resistance of
      particular types of catecholamine neurons to damage.

PMID- 9628758
TI  - Excitatory amino acid-induced degeneration of dendrites of catecholamine neurons
      in rat substantia nigra.
AB  - We have recently established a rat substantia nigra (SN) slice preparation in
      which a sensitive index of excitatory amino acid (EAA) toxicity was degeneration
      of the dendritic arbor of catecholamine neurons labelled by immunostaining for
      tyrosine hydroxylase (TH). The present study examined the pharmacological
      characteristics of EAA-induced neurotoxicity. Rats were anesthetised by halothane
      inhalation and killed, the brain was rapidly removed, and 400-microm-thick SN
      slices cut in the horizontal plane on a vibratome. Slices were incubated in
      saline buffer at 35 degreesC for 15 min to 6 h in the presence or absence or
      absence of kainic acid (KA) or N-methyl-D-aspartate (NMDA) in concentrations
      ranging from 10 to 500 microM. The slices were then fixed and resectioned into 40
      microm sections that were coplanar with the parent slice. Dopaminergic SN neurons
      were labeled using antibody to tyrosine hydroxylase (TH) coupled to
      diaminobenzidine. A feature of the immunostaining was that it labeled not only
      the cell body but also the prolific dendritic arborization of SN neurons.
      Dendritic damage was quantified by counting the proportion of neurons with intact
      dendrites after treatment with EAA. KA and NMDA caused loss of dendrites that was
      prevented by CNQX (20 microM) and MK-801 (20 microM), respectively, indicating
      that activation of either NMDA or non-NMDA receptors produces neurotoxicity. EAA
      induced dendritic damage was observed within 2 h of treatment with a low
      concentration (10 microM) of KA and within 15 min if the concentration was
      increased to 500 microM. Thus the loss of dendrites occurs rapidly and precedes
      disintegration of the cell bodies. Furthermore, brief (15 min) exposure to EAA
      initiated damage in the dendrites which progressed after the EAA was removed from
      its receptor. The observations are consistent with the postulated role of EAAs in
      neurodegenerative diseases. Labeling the dendritic arbor provides a sensitive
      approach to investigating the cellular mechanisms of neurodegeneration of
      catecholamine neurons.

PMID- 9628759
TI  - Absence of association of alpha1-antichymotrypsin polymorphisms with Alzheimer's
      disease: a report on autopsy-confirmed cases.
AB  - alpha1-Antichymotrypsin (ACT) polymorphisms were examined in 79 cases with
      autopsy-confirmed Alzheimer's disease (AD) as well as in 28 cases with autopsy
      confirmed nonneurological diseases to test the hypothesis that ACT polymorphisms
      confer a risk to an individual to develop AD. Neither ACT genotype frequency nor
      ACT allele frequency in the AD group was significantly different from the control
      group. The ACT polymorphic pattern was essentially the same among apolipoprotein
      E (apoE) epsilon4 carriers and noncarriers. The age at onset of AD was not
      significantly affected by the inherited dose of ACT/A allele. Taking together,
      our observations do not confirm the effect of the ACT/A allele as a risk factor
      for developing AD in addition to the ApoE epsilon4 allele.

PMID- 9628760
TI  - Endolymphatic hydrops reduces retrograde labeling of trigeminal innervation to
      the cochlea.
AB  - This paper reports that endolymphatic hydrops causes a significant reduction of
      retrogradely labeled cell bodies of the ipsilateral trigeminal ganglion following
      application of horseradish peroxidase in the cochlea. We previously showed that
      the trigeminal ganglion is a source of primary sensory innervation to the
      cochlear blood vessels. The innervation of the cochlea from the trigeminal
      ganglion may provide the basis of an alternative mechanism for Meniere's syndrome
      (imbalance, hearing loss, tinnitus, and a sensation of fullness in the ear) for
      which a central neural basis has been speculated. Innervation patterns of sensory
      nerves from the trigeminal ganglion to the cochlear blood vessels were studied
      using retrograde transport of wheat germ agglutinin conjugated to horseradish
      peroxidase (WGA-HRP). Healthy and hydropic guinea pigs were unilaterally
      implanted with an osmotic pump and a cannula for cochlear delivery of 2% WGA-HRP
      or vehicle alone. In other guinea pigs the cochlea was pretreated with 100
      micromol capsaicin before administering 2% WGA-HRP. Histological sections of the
      ipsi- and contralateral trigeminal ganglia were obtained 48 h after WGA-HRP
      infusion. In the hydropic guinea pig, the number of labeled nerve cell bodies
      observed in the anteriomedial portion of the trigeminal ganglion at the origin of
      the ophthalmic nerve was reduced by 70% relative to normal animals. Capsaicin
      pretreatment nearly eliminated the labeled sensory fibers as expected. These data
      indicate that the trigeminal innervation to the cochlea could be involved in
      inner ear homeostatic disturbances, including the hydrops that is symptomatic of
      Meniere's disease.

PMID- 9628762
TI  - Preoptic area grafts implanted in mammillary bodies of hypogonadal mice: patterns
      of GnRH neuronal projections.
AB  - Gonadotropin-releasing hormone (GnRH) axons project to the median eminence, where
      the peptide is released to stimulate pituitary gonadotrophs. Hypogonadal mice
      (hpg) do not synthesize GnRH due to a deletion in the gene. When neonatal
      preoptic area (POA) tissue from normal mice containing GnRH neurons is
      transplanted into the third ventricle of hpg mice, GnRH axons exit the graft and
      specifically project to the median eminence, where the release of GnRH in the
      portal circulation induces the stimulation of the pituitary-gonadal axis. To test
      the hypothesis that the median eminence region is critical to targeting, we
      placed POA grafts in the region of the mammillary bodies, which never contains
      GnRH cell bodies, but is nevertheless close to the median eminence. Control mice
      received bilateral grafts into the anterior hypothalamus. GnRH axons innervated
      the median eminence in animals with grafts in the mammillary bodies and posterior
      hypothalamus. Mice with such grafts for 4-5 months had gonadal development, while
      those with grafts for shorter periods did not. Anterior hypothalamic grafts
      merged into the third ventricle and, consistent with previous studies, this
      resulted in GnRH innervation of the median eminence and gonadal development.
      However, when grafts were located within dorsal regions such as the thalamus, no
      median eminence innervation was seen. In these cases, GnRH axons borrowed other
      bundles of fibers to travel within the host brain. The pattern of innervation
      from grafts within ventro-caudal regions of the hypothalamus vs. that from dorsal
      regions supported the hypothesis that the median eminence releases diffusible
      substances directing GnRH outgrowth.

PMID- 9628761
TI  - In vivo L-DOPA production by genetically modified primary rat fibroblast or 9L
      gliosarcoma cell grafts via coexpression of GTPcyclohydrolase I with tyrosine
      hydroxylase.
AB  - To investigate the biochemical requirements for in vivo L-DOPA production by
      cells genetically modified ex vivo in a rat model of Parkinson's disease (PD),
      rat syngeneic 9L gliosarcoma and primary Fischer dermal fibroblasts (FDFs) were
      transduced with retroviral vectors encoding the human tyrosine hydroxylase 2
      (hTH2) and human GTP cyclohydrolase I (hGTPCHI) cDNAs. As GTPCHI is a rate
      limiting enzyme in the pathway for synthesis of the essential TH cofactor,
      tetrahydrobiopterin (BH4), only hTH2 and GTPCHI cotransduced cultured cells
      produced L-DOPA in the absence of added BH4. As striatal BH4 levels in 6
      hydroxydopamine (6-OHDA)-lesioned rats are minimal, the effects of cotransduction
      with hTH2 and hGTPCHI on L-DOPA synthesis by striatal grafts of either 9L cells
      or FDFs in unilateral 6-OHDA-lesioned rats were tested. Microdialysis experiments
      showed that those subjects that received cells cotransduced with hTH2 and hGTPCHI
      produced significantly higher levels of L-DOPA than animals that received either
      hTH2 or untransduced cells. However, animals that received transduced FDF grafts
      showed a progressive loss of transgene expression until expression was
      undetectable 5 weeks after engraftment. In FDF-engrafted animals, no differential
      effect of hTH2 vs hTH2 + hGTPCHI transgene expression on apomorphine-induced
      rotation was observed. The differences in L-DOPA production found with cells
      transduced with hTH2 alone and those cotransduced with hTH2 and hGTPCHI show that
      BH4 is critical to the restoration of the capacity for L-DOPA production and that
      GTPCHI expression is an effective means of supplying BH4 in this rat model of PD.

PMID- 9628763
TI  - Plastic changes in glycine and GABA release and uptake in adult brain stem
      auditory nuclei after unilateral middle ear ossicle removal and cochlear
      ablation.
AB  - [i] In young adult guinea pigs, the effects of unilateral ossicle removal and
      unilateral cochlear ablation were determined on [14C]glycine or [14C]GABA release
      and uptake measured in subdivisions of the cochlear nucleus (CN), the superior
      olivary complex, and the auditory midbrain, after 2 or 5, 59, and 145 postlesion
      days. Activities were compared to those of age-matched, unlesioned controls. [ii]
      [14C]Glycine release declined bilaterally in the anteroventral and dorsal CN
      after ossicle removal and in the dorsal CN after cochlear ablation. [iii]
      Transient elevations of release occurred at 59 days in the ipsilateral
      posteroventral CN ([14C]glycine) and bilaterally in the ventral nucleus of the
      lateral lemniscus ([14C]GABA) after ossicle removal, and bilaterally in the
      medial superior olive ([14C]glycine) after cochlear ablation. [iv] In the medial
      nucleus of the trapezoid body, [14C]GABA release was depressed bilaterally 5 days
      after ossicle removal, but was elevated at 145 days contralaterally after ossicle
      removal and ipsilaterally after cochlear ablation. [v] In the contralateral
      central nucleus of the inferior colliculus, [14C]GABA release was elevated
      persistently after ossicle removal. After cochlear ablation, release was elevated
      at 5 days, near the control at 59 days, and elevated again at 145 days. [vi]
      After both lesions, [14C]glycine uptake was elevated bilaterally in the CN and
      medial superior olive. [14C]GABA uptake became depressed by 59 or 145 days
      bilaterally in the auditory midbrain. [vii] These changes may stem from
      regulation and may contribute to mechanisms that generate symptoms such as
      loudness recruitment and tinnitus, which often accompany hearing loss.

PMID- 9628764
TI  - Impairment of basal forebrain cholinergic neurons associated with aging and long
      term loss of ovarian function.
AB  - Recent studies suggest that women are at greater risk for Alzheimer's disease
      than men and that estrogen replacement can help to reduce the risk and severity
      of Alzheimer's-related dementia in postmenopausal women. We have hypothesized
      that the increased risk for Alzheimer's-related dementia is due, in part, to the
      loss of ovarian function in postmenopausal women and to the effects that
      decreased levels of ovarian hormones have on basal forebrain cholinergic
      function. In the present study, the effects of aging and ovariectomy on
      cholinergic neurons in the rat basal forebrain were examined to determine (1)
      whether aging differentially affects cholinergic neurons in the basal forebrain
      of males vs females, and (2) whether long-term loss of ovarian function produces
      deficits in basal forebrain cholinergic function beyond those associated with
      aging and sex. In part I of the study, gonadally intact male and female rats were
      sacrificed at 13, 19, and 25 months of age and the effects of aging on
      cholinergic neurons in the medial septum (MS) and nucleus basalis magnocellularis
      (NBM) were compared. In part II of the study, female rats were ovariectomized at
      13 months of age and then sacrificed 3 and 6 months later along with gonadally
      intact, age-matched controls. Adjacent sections through the MS and NBM were
      processed for either immunocytochemical detection of choline acetyltransferase
      (ChAT) and p75NTR-like immunoreactivity or for in situ hybridization detection
      and quantification of ChAT and trkA mRNA. Results from part I revealed no
      significant effects of age on the relative size or density of cholinergic neurons
      in the MS and NBM of gonadally intact animals. Likewise, no significant effects
      on the relative numbers of cholinergic neurons expressing p75NTR protein were
      detected. However, a significant decrease in trkA mRNA was detected in the MS of
      gonadally intact females, but not males, between 13 and 25 months of age. No
      significant effects of aging on ChAT mRNA were detected. Results from part II
      revealed significant decreases in both ChAT and trkA mRNA in the MS and NBM of
      female rats sacrificed 6 months, but not 3 months, following ovariectomy relative
      to age-matched, gonadally intact controls. Short-term estrogen replacement
      initiated 6 months following ovariectomy and administered for 3 days prior to
      sacrifice partially restored ChAT mRNA levels in the MS and trkA mRNA levels in
      the NBM. These findings suggest that ovarian hormones play a role in maintaining
      normal levels of ChAT and trkA expression in the MS and NBM. The fact that ChAT
      mRNA was decreased in the MS and NBM at 6 months following ovariectomy suggests
      that long-term loss of ovarian function produces a decrease in the functional
      status of basal forebrain cholinergic neurons projecting to the hippocampus and
      cortex. In addition, we hypothesize that the decreases in trkA mRNA detected both
      in the MS as a function of aging, and in the MS and NBM in response to
      ovariectomy, reflect decreases in the production of high affinity nerve growth
      factor (NGF) receptors, and a decrease in the responsiveness of the cholinergic
      neurons to endogenous NGF. This, in turn, may increase the susceptibility of the
      cholinergic neurons to the effects of aging and disease and thereby contribute to
      basal forebrain cholinergic decline. We conclude that long-term loss of ovarian
      function combined with aging has a negative impact on basal forebrain cholinergic
      neurons. These effects may contribute to the risk and severity of cognitive
      decline associated with aging and Alzheimer's disease in postmenopausal women.

PMID- 9628765
TI  - A quantifiable model of axonal regeneration in the demyelinated adult rat spinal
      cord.
AB  - Strategies to increase the extent of axonal regeneration in the adult CNS must
      address an array of intrinsic and environmental factors which influence neuritic
      outgrowth. In order to develop an in vivo model of axonal regeneration in which
      potential therapies may be assessed, we have quantified growth cones within
      demyelinated regions in the dorsal funiculus of the spinal cord, following a
      discrete axotomy. Demyelinated lesions were produced by the intraspinal injection
      of galactocerebroside antibodies plus serum complement proteins. Axonal integrity
      was not compromised by the demyelination protocol. Axonal injury was induced at
      the caudal extent of the demyelinated region using a micromanipulator-controlled
      Scouten knife. The severity of axonal injury was varied in different animals at
      the time of surgery and was quantified 8 days later by counting degenerate axons
      in transverse 1-microm resin sections. Evidence of axonal regeneration within
      these animals was assessed by an electron microscopic analysis of growth cone
      frequency and position relative to the site of axotomy. Growth cones were
      identified within the region of demyelination only; no growth cones were
      identified within the dorsal column white matter adjacent to the demyelinated
      region, or rostral or caudal to the region of demyelination, or in animals with
      an injury but no demyelination. Quantification of growth cones within regions of
      demyelination indicated a strong linear relationship (P < 0.001) between the
      number of growth cones and the number of axons severed. These findings indicate
      that demyelination facilitates axonal regeneration in the adult rat CNS and
      illustrate a quantifiable method of assessing axonal regeneration.

PMID- 9628766
TI  - Evidence for normal aging of the septo-hippocampal cholinergic system in apoE (-/
      ) mice but impaired clearance of axonal degeneration products following injury.
AB  - The association of the epsilon4 allele of apoE with increased risk for
      Alzheimer's disease (AD) and with poor clinical outcome after certain acute brain
      injuries has sparked interest in the neurobiology of apoE. ApoE (-/-) mice
      provide a tool to investigate the role of apoE in the nervous system in vivo.
      Since integrity of the basal forebrain cholinergic system is severely compromised
      in AD, with severity of dysfunction correlating with apoE4 gene dosage, the
      present study tested the hypothesis that apoE is required to maintain the normal
      integrity of basal forebrain cholinergic neurons (BFCNs). Histological and
      biochemical analyses of the septo-hippocampal cholinergic system were performed
      in apoE (-/-) mice during aging and following injury. Using unbiased quantitative
      methods, there was little or no evidence for defects in the septo-hippocampal
      cholinergic system, as assessed by p75(NTR)-immunoreactive neuron number and size
      in the medial septum, cholinergic fiber density in the hippocampus, and choline
      acetyltransferase activity in the hippocampus, cortex, and striatum in aged apoE
      (-/-) mice (up to 24 months of age) as compared to age-matched wild-type mice of
      the same strain. In addition, cholinergic neuronal survival and size following
      fimbria-fornix transection in apoE (-/-) mice did not differ from controls.
      However, following entorhinal cortex lesion, there was persistence of
      degeneration products in the deafferented hippocampus in apoE (-/-) mice. These
      data suggest that although apoE is not required for the maintenance of BFCNs in
      vivo, it may play a role in the clearance of cholesterol-laden neurodegeneration
      products following brain injury.

PMID- 9628767
TI  - Alterations in potassium currents may trigger neurodegeneration in murine
      scrapie.
AB  - Conventional electrophysiological intracellular recording techniques were used to
      test the hypothesis that enhanced calcium entry via voltage-gated calcium
      channels or the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor-channel
      complex may be a primary pathological mechanism triggering neurodegeneration in
      scrapie and related diseases. This study was carried out at a time when cell loss
      is known to occur and when hippocampal pyramidal cells in area CA1 are rendered
      hyperexcitable following scrapie infection. There was no change to the NMDA
      receptor-mediated component of the Schaffer collateral evoked excitatory
      postsynaptic potential (EPSP) or the level of spontaneous firing activity of CA1
      cells following addition of the specific NMDA receptor antagonist, 2-amino-5
      phosphonovaleric acid (APV, 20 microM), to the perfusate in scrapie-infected
      mice, indicating that the NMDA receptor-channel complex is not compromised by
      scrapie. There was also no change seen in the non-NMDA mediated component of the
      EPSP. The calcium spike of CA1 pyramidal cells was not significantly altered by
      scrapie infection, indicating that high threshold voltage-gated Ca2+ channel
      function is not compromised by scrapie. By contrast, cells from scrapie-infected
      mice fired calcium spikes repetitively and the long, slow AHP, which in control
      cells inhibited repetitive firing, was absent. Cells from scrapie-infected mice
      showed more depolarized membrane potentials than controls but this difference in
      potential was no longer observed after exposure to TEA. These data indicate a
      loss of TEA-insensitive and TEA-sensitive potassium conductances. We suggest that
      altered potassium currents rather than increased calcium entry via voltage
      sensitive calcium channels or the NMDA receptor complex may be the primary
      pathological mechanism triggering neurodegeneration in scrapie and related
      diseases.

PMID- 9628769
TI  - The effect of age and testosterone on the expression of glial fibrillary acidic
      protein in the rat cerebellum.
AB  - Testosterone reversed the age-related increase in glial fibrillary acidic protein
      (GFAP) in the male rat cerebellum, a brain region not generally associated with
      gonadal steroid hormone sensitivity. This supports the hypothesis that a decrease
      in circulating testosterone contributes to age-related increase in GFAP. These
      data also suggest that reductions in circulating gonadal steroids during aging
      could render the brain more susceptible to neurodegeneration and that hormone
      replacement therapy might have value in neurodegenerative disease intervention.

PMID- 9628768
TI  - Characterization of enhanced behavioral responses to L-DOPA following repeated
      administration in the 6-hydroxydopamine-lesioned rat model of Parkinson's
      disease.
AB  - Long-term treatment of Parkinson's disease with dopamine-replacing agents such as
      L-3,4-dihydroxyphenylalanine (L-DOPA) is compromised by many side-effects, most
      notably involuntary movements, L-DOPA-induced dyskinesia. Acute challenge with
      dopamine-replacing drugs elicits a rotational response in the 6-hydroxydopamine
      (6-OHDA)-lesioned rat model of Parkinson's disease. This rotation is
      contraversive to the lesion and is considered to represent an antiparkinsonian
      effect. More recently, it has become clear that the rotational response shows
      plasticity and that repeated L-DOPA or apomorphine therapy is accompanied by a
      marked enhancement in this response. In this study, we demonstrate that the
      enhanced behavioral response to repeated dopamine-replacement therapy seen in the
      6-OHDA-lesioned rat has pharmacological characteristics similar to L-DOPA-induced
      dyskinesia seen in MPTP-lesioned primates and man. Thus, the magnitude and rate
      of development of the enhanced response to L-DOPA treatment is related to both
      the number of doses and the size of the dose of L-DOPA administered. In contrast,
      de novo administration of dopaminergic drugs that are associated with a lower
      incidence of dyskinesia, e.g., bromocriptine or lisuride, does not lead to an
      enhanced behavioral response following repeated treatment. However, following a
      single "priming" administration of apomorphine, the rotational response elicited
      by subsequent bromocriptine administrations is enhanced with repeated treatment.
      Once established, the enhanced behavioral response to repeated L-DOPA
      administration (6.5 mg/kg, twice daily) can, like L-DOPA-induced dyskinesia in
      man and MPTP-treated monkeys, be selectively reduced by coadministration of L
      DOPA with the alpha2-adrenergic receptor antagonist yohimbine (10 mg/kg, -95%),
      the 5-HT uptake inhibitor 5-MDOT (2 mg/kg, -90%), or the beta-adrenergic receptor
      antagonist propranalol (10 mg/kg, -35%). While these rats do not exhibit symptoms
      of dyskinesia per se, this rodent model does exhibit behaviors, the underlying
      mechanism of which is likely to be similar to that underlying L-DOPA-induced
      dyskinesia and may prove useful in studying the molecular and cellular mechanisms
      of L-DOPA-induced dyskinesia in Parkinson's disease.

PMID- 9628770
TI  - Announcement 
AB  - Copyright

PMID- 9628798
TI  - Mucin-like glycoprotein secretion is mediated by cyclic-AMP and protein kinase C
      signal transduction pathways in rat corneal epithelium.
AB  - Ocular surface mucin is secreted from both goblet cells in the conjunctival
      epithelium and corneal epithelial cells. To clarify its mechanism of secretion in
      corneal epithelial cells, a rat cornea organ culture system was used to evaluate
      the second messenger roles of cyclic-AMP (cAMP), cyclic-GMP (cGMP) and protein
      kinase C (PKC) in modulating mucin-like glycoprotein secretion. Rat cornea
      sections (3 mm diameter) were cultured in TC-199 medium, and radiolabeled with
      sodium sulfate for 18 hr. After washing, the corneas were treated with various
      second messenger modulating agents for 30 min. The culture media were reacted
      with Dolichos biflorus (DBA)-lectin, and mucin-like glycoprotein was isolated.
      Then the radioactivity of DBA-binding mucin-like glycoprotein was isolated. Then
      the radioactivity of DBA-binding mucin-like glycoprotein was measured. There was
      a time-dependent increase in mucin-like glycoprotein was measured. There was a
      time-dependent increase in mucin-like glycoprotein secretion, whereas after
      corneal epithelial debridement the secretion was markedly inhibited by 81%. Mucin
      like glycoprotein secretion was stimulated in a dose-dependent manner following
      elevation of cAMP levels by exposure to either forskolin, dibutyryl cAMP or 3
      isobutyl-1-methylxanthine. Concomitant exposure to the cAMP dependent protein
      kinase inhibitor, KT5720 completely inhibited their stimulatory effects. Neither
      exposure to dibutyryl cGMP nor nitroprusside affected mucin-like glycoprotein
      secretion. Stimulation by PKC, phorbol 12, 13-dibutyrate (PDBu) also increased
      mucin-like glycoprotein secretion in a dose-dependent fashion. The PKC inhibitor,
      calphostin C completely inhibited the stimulation by PDBu of mucine-like
      glycoprotein secretion. These results demonstrate that corneal epithelial cells
      secrete mucin-like glycoprotein, which is mediated by cAMP and PKC signal
      transduction pathways.

PMID- 9628799
TI  - Apoptosis and morphologic changes in drug-treated trabecular meshwork cells in
      vitro.
AB  - Using an in vitro culture system, we investigated whether bovine trabecular
      meshwork cells undergo apoptosis (programmed cell death) following exposure to
      anti-glaucoma medications (timolol, pilocarpine and epinephrine) and known
      inducers of apoptosis (5-fluorouracil, mitomycin-C and dexamethasone). Third to
      fifth passage bovine trabecular meshwork cells were grown to confluence and
      incubated for 1-12 days in growth media with timolol (1-1000 microM), pilocarpine
      (15-15,000 microM), epinephrine (5-5000 microM), 5-fluorouracil (10-100
      micrograms ml-1), mitomycin-C (0.01-100 micrograms ml-1) and dexamethasone (0.01
      100 microM). The cultures were evaluated for apoptosis by phase-contrast
      microscopy, transmission electron microscopy and in situ apoptosis labeling. 5
      Fluorouracil (10-100 micrograms ml-1), mitomycin-C (0.1-100 micrograms ml-1) and
      epinephrine (500-5000 microM) induced apoptosis in a dose and time-dependent
      manner. Timolol, pilocarpine, and dexamethasone-treated specimens did not show
      evidence of apoptosis at any of the concentrations tested. Trabecular meshwork
      cells incubated in timolol (100-1000 microM) developed cytoplasmic granules, and
      specimens treated with pilocarpine (15,000 microM) developed cytoplasmic
      vacuoles. These granules and vacuoles have the appearance of secondary lysosomes.
      Dexamethasone-treated cells developed an increased number of mitochondria. This
      study suggests that the trabecular meshwork may undergo apoptosis following
      exposure to 5-fluorouracil, mitomycin-C and epinephrine. Timolol, pilocarpine and
      dexamethasone did not induce apoptosis. However, these drugs can incite
      characteristic morphologic changes in cultured trabecular meshwork cells.

PMID- 9628800
TI  - Novel inhibitors against the transglutaminase-catalysed crosslinking of lens
      proteins.
AB  - Post-translational modifications by transglutaminase may contribute to the
      remodeling of cellular architecture in the development of lens fiber cells, and
      there is evidence that the enzyme may also play a role in cataract formation. It
      catalyses hydrolytic deamidations as well as amide exchanges on select glutamine
      side chains at endo positions in a small subset of proteins of the lens. N
      epsilon(gamma-glutamyl)lysine crosslinks, the characteristic hallmarks of
      transglutaminase activity, were identified in polymers isolated from human
      cataract. Following up on our earlier studies relating to the inhibition of
      protein crosslinking by the Ca(2+)-activated transglutaminase in the lens, we
      have now examined the effects of 2-[(2-oxopropyl)thio]-imidazolium derivatives,
      recently described as active site-directed inhibitors for this family of enzymes.
      First, we have shown that the compounds at concentrations of 1-2 microM were
      effective in blocking the transamidating activities of partially purified lens
      transglutaminase. Then we focused on their efficacy in preventing the formation
      of the ca. 55 kDa beta crystallin dimers in the whole lens tissue. The production
      of these dimers, crosslinked by N epsilon(gamma-glutamyl)lysine isopeptide
      bridges, is an early sign of transglutaminase action in rabbit lens, and it can
      be readily documented by the SDS-PAGE analysis of proteins remaining in the
      soluble phase after brief exposure of the homogenate to Ca2+. The new compounds
      proved to be potent inhibitors of transglutaminase also in this preparation,
      preventing the crosslinking event at ca. 1 microM concentration. Moreover, even
      when applied at a 1,000-fold greater concentration (2 mM), they did not interfere
      with the action of calpain which, similarly to the activation of the
      transglutaminase system, is triggered by the addition of Ca2+. The high
      selectivity of the new compounds for differentially blocking only the
      transglutaminase and not the calpain of the lens, is all the more remarkable
      because these two enzymes share several mechanistic and structural similarities.

PMID- 9628801
TI  - Glutamine immunoreactivity in Muller cells of monkey eyes with experimental
      glaucoma.
AB  - The action of glutamate in retina is largely terminated through rapid uptake by
      Muller cells and subsequent conversion primarily to glutamine. Glutamine,
      transferred from Muller cells to neurons, serves as a precursor for the formation
      of glutamate in neurons completing the glutamate-glutamine cycle. In a monkey
      model of high-tension glaucoma, we have examined glutamine immunoreactivity in
      the Muller cell as well as the number of Muller cells to determine whether the
      activity of these cells in the glutamate-glutamine cycle is affected,
      particularly since high vitreal glutamate has been reported in glaucoma.
      Unilateral glaucoma was induced in three monkeys by argon laser application to
      the trabecular meshwork. LR White sections of retina from the temporal mid
      periphery (about 23 degrees) and the parafovea (central 3 degrees) were
      immunolabeled for glutamine using immunogold and silver intensification. The
      percentage difference in labeling intensity (darkness) in the glaucomatous retina
      was determined relative to the labeling found in the control retina by image
      analysis. Ganglion cell density was estimated from radial sections in the
      parafovea and from retinal whole mounts in the mid-periphery. The number of
      Muller cells was estimated from vibratome sections immunolabeled by vimentin
      antibodies in the temporal mid-periphery (about 30 degrees). Glutamine
      immunoreactivity was localized predominately in ganglion cells and Muller cells.
      However, the intensity of glutamine immunolabeling was greater in Muller cells of
      glaucomatous eyes than in control eyes. This increase in glutamine immunolabeling
      was 25-32% in the temporal mid-periphery and 27-48% in the parafovea. Muller cell
      number in the glaucomatous eye was similar to that of the control in the temporal
      mid-periphery. The data in this study indicate that the increase in glutamine in
      Muller cells is not a consequence of their loss and that Muller cell function in
      the glutamate-glutamine cycle continues in glaucomatous eyes. These findings are
      consistent with a previous report that extracellular/vitreal glutamate
      concentration is elevated in high-tension glaucoma.

PMID- 9628802
TI  - Involvement of TNF alpha, IL-1 beta and IL-1 receptor antagonist in LPS-induced
      rabbit uveitis.
AB  - The objective of the study was to investigate involvement of TNF alpha, IL-1 beta
      and IL-1 receptor antagonist (IL-1Ra) in lipopolysaccharide (LPS)-induced
      uveitis. Intravitreal injection of LPS (100 ng) to rabbits induced a massive
      leukocyte infiltration and protein leakage into the aqueous humor. Aqueous
      leukocyte counts and protein levels reached a peak 24 hr after this injection.
      The peak concentrations of aqueous TNF alpha (230 +/- 37 pg ml-1, at 9 hr) and IL
      1 beta (185 +/- 80 pg ml-1, at 18 hr) preceded peak levels of aqueous leukocyte
      counts and protein levels. In contrast, the levels of aqueous IL-1Ra peaked at 48
      hr (12,239 +/- 1964 pg ml-1) and a fairly high concentration of IL-1Ra remained
      when the inflammatory reactions subsided. Immunohistochemistry and leukocyte
      depletion studies showed that infiltrating leukocytes were the major cellular
      sources of aqueous TNF alpha, IL-1 beta and IL-1Ra. Intravitreal injection of
      homologous TNF alpha (0.1-1.5 micrograms) or IL-1 beta (0.5-5 ng) reproduced a
      rapid leukocyte infiltration and protein leakage. Administration of anti-TNF
      alpha mAb (10 micrograms) suppressed the number of LPS-induced infiltrating
      neutrophils by 50%, mononuclear cells by 58%, and protein leakage by 42%.
      Administration of rabbit IL-1Ra (10 micrograms) also suppressed neutrophil influx
      by 78%, however, neither mononuclear cell influx nor protein leakage was
      inhibited by rabbit IL-1Ra. Co-administration of the two inhibitors enhanced
      inhibition of neutrophil infiltration to 88%, and protein leakage to 64%. We
      conclude that TNF alpha and IL-1 beta are the principal mediators of LPS-induced
      uveitis. Our observations also suggest that endogenous IL-1Ra may down-regulate
      inflammatory reactions.

PMID- 9628803
TI  - Influence of cholesterol on the interaction of alpha-crystallin with
      phospholipids.
AB  - The influence of cholesterol on the binding of alpha-crystallin to pure
      phospholipid membranes was studied. The rationale of this investigation stems
      from two unique aspects of human lens cells: an unusually high level of
      cholesterol in the membranes and the specific binding of alpha-crystallin to
      membranes. In the absence of cholesterol, binding of alpha-crystallin liposomes
      composed of either sphingomyelin, disteroyl-phosphatidylcholine or egg
      phosphatidylcholine caused a decrease in the fluorescence intensity and
      anisotropy of the fluorophore NBD-PE. Since this fluorescence probe resides in
      the polar headgroup region of the membrane, the observed changes indicated that
      the binding of alpha-crystallin affected the structure of these membrane regions.
      The ability of alpha-crystallin to modulate membrane structure suggests yet
      another potential role for this lens protein. Addition of cholesterol markedly
      decreased the binding of alpha-crystallin to liposomes composed of either
      sphingomyelin or disteroylphosphatidylcholine and antagonized the capacity of
      bound alpha-crystallin to decrease membrane surface order. This antagonism could
      be explained by the ability of cholesterol to directly decrease the anisotropy of
      the fluorophore in sphingomyelin membranes unexposed to alpha-crystallin. Thus,
      with cholesterol present, a further decrease in membrane order upon subsequent
      binding of alpha-crystallin was less likely. The results obtained with the
      sphingomyelin liposomes are considered most meaningful, since sphingomyelins are
      the principal phospholipids in the human lens nuclear membrane and cholesterol
      preferentially interacts with sphingomyelin. We conclude that cholesterol in
      lipid membranes can antagonize the binding of alpha-crystallin and thus interfere
      with the capacity of bound alpha-crystallin to alter membrane order. We suggest
      that such actions of cholesterol might serve to preserve lens membrane structure
      in the physiological state where the concentration of soluble alpha-crystallin is
      great.

PMID- 9628804
TI  - The role of laminin-5 in TGF alpha/EGF-mediated corneal epithelial cell motility.
AB  - Transforming growth factor alpha (TGF alpha) and epidermal growth factor (EGF)
      stimulate corneal epithelial cell wound closure. However, the role of these
      growth factors in regulating corneal epithelial cell motility on basement
      membrane proteins such as laminin has not been elucidated. In the present study
      we demonstrate that in an in vitro model of corneal wound healing, TGF alpha has
      no deleterious effects on the deposition of the laminin-5 isoform into the
      extracellular matrix structure underlying epithelial cells resurfacing bare
      collagenous stroma. In primary culture, a population of corneal epithelial cells
      are stimulated by TGF alpha or EGF to become highly motile. These cells are
      associated with an endogenously secreted, and extracellularly deposited, 'trail'
      of laminin-5. The laminin-5 trail is specifically associated with motile cells,
      as non-motile corneal epithelium exhibiting numerous cell-cell contacts does not
      display a similar laminin-5 localization pattern. In contrast to these
      observations, a preparation of laminin-5 known to promote cell spreading,
      adhesion, and formation of hemidesmosomes, when presented exogenously to cultured
      corneal epithelial cells, does not stimulate motility. However, a commercially
      available preparation of laminin derived from human placenta which does not
      contain laminin-5 does significantly promote the migration of TGF alpha- or EGF
      stimulated corneal epithelial cells. From these results, it is hypothesized that
      endogenously secreted laminin-5 functions to promote migration in corneal
      epithelial cells which have been treated with TGF alpha or EGF. Exogenously
      presented laminin-5 does not function similarly, but functions to promote corneal
      epithelial cell adhesion.

PMID- 9628805
TI  - A c-myc antisense oligonucleotide inhibits human retinal pigment epithelial cell
      proliferation.
AB  - The purpose of this work was to investigate if MYC-dependent intracellular
      mitogenic pathway is active in cultures of human retinal pigment epithelial
      (hRPE) cells and whether myc antisense phosphorotioate oligonucleotides (c-myc-AS
      ODN) are useful tools for inhibiting the proliferation of hRPE cells. Cultures of
      hRPE cells were established from adult human corneal donors. These cells were
      positively stained for cytokeratins and vimentin. Myc mRNA expression was
      determined by Northern blot analysis and it was determined by means of
      immunofluorescence if MYC was expressed. C-myc-AS-ODN effect on cell
      proliferation was estimated by evaluating the incorporation of 5-bromo-2'-deoxy
      uridine into cellular DNA. Cell number was estimated by using a tetrazolium
      bromide based colorimetric method. Human RPE cells in culture expressed MYC and
      myc mRNA as well as prothymosin alpha mRNA--a gene whose transcription is under
      MYC control--indicating that MYC-dependent intracellular mitogenic pathway is
      active in these cells. In accordance with this, we found that blocking the
      expression of myc by the addition of c-myc-AS-ODN to the culture medium inhibited
      hRPE cell proliferation. The effect of the c-myc-AS-ODN was found to be sequence
      specific (the use of a control oligonucleotide with the same sequence but in an
      opposite direction had no effect) and dose-dependent (4 microM was the lowest
      effective dose tested). By using RT-PCR we found that the c-myc-AS-ODN inhibition
      of cell proliferation was related to a diminution in c-myc mRNA expression, and
      by immunofluorescence we detected a diminution in c-MYC protein staining in RPE
      cells after 48 hr of treatment with c-myc-AS-ODN. Furthermore, growth inhibition
      remained for at least 5 days after addition of a single dose of the c-myc-AS-ODN
      to the culture. We conclude that hRPE cell proliferation is under MYC control.
      Blocking the expression of myc by c-myc-AS-ODN inhibited hRPE cell proliferation.
      These findings establish a rationale for investigating the potential use of a c
      myc-AS-ODN as a novel therapeutical tool in the treatment of Proliferative
      Vitreoretinopathy.

PMID- 9628806
TI  - Monoamine oxidase-A-positive retinal ganglion cells projecting to the superior
      colliculus and dorsolateral geniculate nucleus of the rat brain.
AB  - Detailed morphology and distribution of monoamine oxidase type A (MAO-A) positive
      retinal ganglion cells, and their synaptic terminals in the superior colliculus
      and the lateral geniculate nucleus, were investigated by light and electron
      microscopy. In addition, the differences in various retinal ganglion cells with
      respect to the projection site were examined by the injection of colloidal gold
      into the superior colliculus and the lateral geniculate nucleus. The effects of
      unilateral enucleation were also examined. In the retina, small, medium and large
      sized MAO-A-positive ganglion cells were observed; the large sized cells were
      distributed evenly throughout the retina, while the small and medium sized cells
      were most numerous in a ring surrounding the central retina and decreased in
      density near the optic disc and the peripheral retina. The MAO-A-positive
      terminals in the superior colliculus were smaller in size than those in the
      lateral geniculate nucleus. From colloidal gold injection, it was apparent that
      the MAO-A-positive ganglion cells projecting to the superior colliculus were
      generally smaller in size than those projecting to the lateral geniculate
      nucleus. Fourteen days after unilateral enucleation, the MAO-A-positive terminals
      in the superior colliculus and lateral geniculate nucleus contralateral to the
      enucleated eye had almost disappeared, whereas those in the ipsilateral regions
      remained unaffected. These findings demonstrate the distribution and projections
      of the MAO-A-positive ganglion cells.

PMID- 9628807
TI  - Enhancement of opsin activity by all-trans-retinal.
AB  - The rod cell photoreceptor apoprotein, opsin, activates the G-protein,
      transducin, although at a much reduced level than light-activated rhodopsin. The
      ability of all-trans-retinal to enhance opsin apoprotein activity was
      investigated using a guanyl nucleotide exchange assay on transducin. All-trans
      retinal enhanced opsin activity in a concentration-dependent manner. At high
      concentrations of all-trans-retinal, the activity of the all-trans-retinal-opsin
      complex was comparable to that from an equimolar amount of metarhodopsin(II).
      However, in contrast to metarhodopsin(II), the active all-trans-retinalopsin
      complex did not require a stable Schiff base linkage between opsin and all-trans
      retinal. The lack of a stable Schiff base and differences in activity at high pH
      imply that opsin and all-trans-retinal form a complex that is distinct from
      metarhodopsin(II). The ability of all-trans-retinal to stimulate the transduction
      cascade may be a source of post-bleach noise in photoreceptors.

PMID- 9628809
TI  - Reduction in water permeability of the rabbit conjunctival epithelium by
      hypotonicity.
AB  - The effects of unilateral exposure to hypotonic media on the diffusional water
      permeability of the isolated rabbit conjunctiva were determined. For these
      experiments, a segment of the bulbar-palpebral conjunctiva was mounted between
      Ussing-type hemichambers under short-circuited conditions. Unidirectional
      diffusional water fluxes (Jdw) were measured in either direction by adding 3H2O
      to one hemichamber and sampling from the other. Electrical parameters were
      measured simultaneously. Jdw were determined in control isosmotic conditions and
      after dilution of one of the bathing solutions from 290 to 108 mOsMolar. This
      hypotonic condition reduced Jdw by 25-30% (n = 17) when applied basolaterally and
      by 25% (n = 6) apically. The effects were reversible and were also obtained when
      the opposite bathing solution contained amphotericin B, selectively
      permeabilizing the contralateral cell surface. From concomitant changes in
      transepithelial electrical resistance as well as 14C-mannitol fluxes completed
      under identical conditions, arguments are presented that the above effect is best
      explained as a cell regulated reduction in membrane water permeability.
      Presumably both apical and basolateral membranes can down-regulate their water
      permeabilities. This response, suggesting a protective mechanism to help maintain
      cell volume from hypotonicity, was also seen in other studies using the amphibian
      bladder and the frog cornea, in which the effect was only obtained basolaterally.
      Thus, regulation of epithelial water permeability appears to be a basic trait
      common to both amphibians and mammals, although tissue differences exist.

PMID- 9628808
TI  - Connexin50, a gap junction protein of macrogliaP6n the mammalian retina and
      visual pathway.
AB  - Reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting and
      immunocytochemistry were used to study the expression of gap junction proteins
      (connexins; Cx) in the rat and rabbit retina. RT-PCR of rabbit total retinal RNA
      using primers selected for the human Cx50 (alpha 8 Cx) DNA template yielded cDNA
      fragments of the predicted base pair size. Western blots of rat and rabbit
      retinal membrane preparations probed with a monoclonal antibody which recognizes
      Cx50 in the lens of several mammalian species revealed a single band (MW 50 kD),
      identical to that recognized in lens membrane extracts. In frozen retinal
      sections of both species, the same monoclonal antibody as well as two polyclonal
      antisera raised against a synthetic peptide from the C-terminal region of the
      human Cx50 polypeptide labeled Muller cells and astrocytes. In Muller cells,
      labeling was strongest in the endfeet and in the filamentous processes
      ensheathing the photoreceptors. Extending from the neural retina, Cx50-like
      immuno-reactivity was detected in astrocytes of the optic nerve and along retinal
      projections within the CNS. Our data indicate that Muller cells and astrocytes of
      mammalian retinas and throughout the visual pathway are coupled through gap
      junctions composed of connexin50.

PMID- 9628810
TI  - Primary sequence, secondary structure, gene structure, and assembly properties
      suggests that the lens-specific cytoskeletal protein filensin represents a novel
      class of intermediate filament protein.
AB  - The ocular lens fiber cell assembles a novel cytoskeletal element, the Beaded
      Filament, from CP49 and filensin, two proteins expressed only in the
      differentiated lens fiber cell. We report the primary sequence, secondary
      structural analysis, gene structure and Yeast Two Hybrid interaction data for
      human filensin, and develop a consensus model of filensin from the human and
      previously reported bovine and chicken filensin sequences. This consensus model,
      combined with gene structure and Yeast Two Hybrid studies establish that filensin
      is a member of the Intermediate Filament family of proteins. Specifically,
      filensin exhibits (1) divergence at amino acid sequence motifs otherwise highly
      conserved among intermediate filament proteins, (2) a loss of 29 amino acids from
      the central rod domain which is unique among cytoplasmic intermediate filament
      proteins, (3) an absence of sequence identity with any existing class of
      intermediate filament protein, (4) a gene structure unique among intermediate
      filament family, (5) an inability to dimerize with representatives of Type I, II,
      and III intermediate filament proteins. Thus, at each level of analysis, we find
      that filensin is similar to the consensus model of intermediate filament
      proteins, supporting our conclusion that filensin's relatedness to the IF family
      is not the consequence of convergent evolution. However, filensin also shows
      unique or extreme distinctions from the consensus intermediate filament protein
      at each level of analysis, indicating that filensin constitutes a novel class of
      IF protein. Some of filensin's unique features are incompatible with current
      models of IF assembly. Analysis of filensin gene structure suggests that the 29
      amino acid reduction in the central rod domain was not the result of a single
      splice site mutation, the mechanism suggested for the transition between nuclear
      lamins and cytoplasmic intermediate filament proteins.

PMID- 9628811
TI  - Cholesterol oxides accumulate in human cataracts.
AB  - Human lens membranes contain the highest cholesterol content of any known
      biological membrane. Although cholesterol is prone to oxidation, the presence of
      its oxidation products in human cataract has not been shown before. This study
      was designed to investigate the presence of cholesterol oxides in human
      cataractous lenses. Human clear lenses (n = 48) were obtained from Coimbra
      University Hospital Eye Bank. Human cataracts (n = 54) were obtained by routine
      extracapsular surgery. Cholesterol oxides were isolated by solid-phase extraction
      on a C18 cartridge and quantified as TMS-ether derivatives by gas chromatography.
      The extraction procedure allows for an efficient recovery of the major
      cholesterol oxides, while retaining virtually all cholesterol. Exposure of
      membranes isolated from transparent human lenses to the free radical generator
      2,2'-Azobis(2-amidinopropane) dihydrochloride (AAPH) produced 7 alpha
      hydroxycholesterol (6%), 7 beta-hydroxycholesterol (19%), 5 alpha, 6 alpha
      epoxycholestanol (1%) and 7-ketocholesterol (74%) as major oxidation products.
      Cataractous lenses contained quantifiable amounts of 7 beta-hydroxycholesterol
      (7.3 +/- 0.74 mmol mol-1 cholesterol), 7-ketocholesterol (4.2 +/- 0.32 mmol mol-1
      cholesterol), 5 alpha, 6 alpha-epoxycholestanol (0.9 +/- 0.16 mmol mol-1
      cholesterol), 20 alpha-hydroxycholesterol (0.6 +/- 0.13 mmol mol-1 cholesterol)
      and 25-hydroxycholesterol (0.1 +/- 0.02 mmol mol-1 cholesterol), whereas clear
      lenses contained no detectable amounts of cholesterol oxides. We have shown, for
      the first time, that oxysterols accumulate in human cataracts. Although the total
      amount of oxidized cholesterol in cataracts is not likely to be high it may
      account for much of the membrane damage associated with cataract formation.

PMID- 9628812
TI  - The effect of light deprivation on the mouse lens.
AB  - This work was undertaken to test the hypothesis that first exposure of the eye to
      light is responsible for the changes in lens protein expression patterns observed
      around the time of birth. The effect of light deprivation on lens properties was
      examined in Balb c mice which were bred, reared and maintained in complete
      darkness for up to 7 months. Data were collected on body weight, lens weight,
      lens protein contents and crystallin distributions. The data were compared with
      those obtained from age matched mice maintained in natural light/dark conditions.
      No significant differences were observed in body weight between animals
      maintained in the light and dark. However, animals kept in the dark had
      significantly smaller lenses. After 6 months in the dark, the lens represented
      0.02% of body weight compared with 0.031% in the light reared animals (P <
      0.001). Lens protein concentration, insoluble protein contents and crystallin
      synthesis patterns were indistinguishable for the two groups of animals. It is
      concluded that light stimulation of the eye is required for optimal lens growth
      but does not affect the production of specific crystallins.

PMID- 9628813
TI  - Relationship between orthogonal arrays of particles in the rat ciliary epithelium
      and maturation of the blood-aqueous barrier.

PMID- 9628814
TI  - Effects of light and dark environment on regeneration of carp optic nerves.

PMID- 9628816
TI  - Construction of a high-resolution physical and transcription map of chromosome
      16q24.3: a region of frequent loss of heterozygosity in sporadic breast cancer.
AB  - A breast cancer tumor suppressor gene has been localized to chromosome 16q24.3 by
      loss of heterozygosity (LOH) studies of breast tumor DNA. To identify candidate
      genes for this suppressor function, we have constructed a detailed physical map
      extending approximately 940 kb from the telomere of the long arm of chromosome 16
      that encompasses the minimum LOH interval. This contig consists of a minimum
      overlapping set of 35 cosmids and a single PAC clone that were aligned by
      restriction enzyme site mapping. Cosmids were initially identified by screening
      filters with markers localized to the region by physical mapping using
      mouse/human somatic cell hybrids, and subsequently cosmid ends were used to
      complete the contig. A total of seven known genes, including PRSM1, PISSLRE, and
      the recently cloned Fanconi anemia A (FAA) gene, and potential transcripts from
      exon-trapping experiments have been located to this contig. A minimum of 14 new
      transcripts have been identified based on homology of trapped exons with database
      sequences. This contig and expressed sequence map will form the basis for the
      identification of the breast cancer tumor suppressor gene in this region.

PMID- 9628817
TI  - Hotfoot mouse mutations affect the delta 2 glutamate receptor gene and are
      allelic to lurcher.
AB  - Hotfoot (ho) is a recessive mouse mutation characterized by cerebellar ataxia
      associated with relatively mild abnormalities of the cerebellum. It has been
      previously mapped to Chromosome 6, and at least eight independent alleles have
      been reported. Here we show that the hotfoot phenotype is associated with
      mutations in the glutamate receptor ionotropic delta2 gene (Grid2). We have
      identified a 510-bp deletion in the Grid2 coding sequence in the ho4J allele,
      resulting in a deletion of 170 amino acids of the extracellular domain of the
      receptor. Analysis of a second allele, hoTgN37INRA, revealed a 4-kb deletion in
      the Grid2 transcript. The GRID2 protein in these hotfoot mutants probably has a
      reduced (or null) activity since the phenotype of hotfoot bears similarities with
      the previously described phenotype of Grid2 knockout mice. The exceptionally high
      number of independent alleles at the ho locus is an invaluable tool for
      investigating the function of the glutamate receptor ionotropic delta2 protein,
      which so far remains largely unknown.

PMID- 9628818
TI  - Calcium channel beta 4 (CACNB4): human ortholog of the mouse epilepsy gene
      lethargic.
AB  - The mouse neurological mutant lethargic (lh) is characterized by ataxia, focal
      myoclonus, and absence epilepsy due to a loss-of-function mutation in the beta4
      subunit of the voltage-gated calcium channel. To evaluate the role of this
      channel subunit in human neurological disease, we determined the chromosomal
      location and intron/exon structure of the human CACNB4 gene. The 1560-bp open
      reading frame of the CACNB4 cDNA predicts a 58-kDa protein with an amino acid
      sequence that is 99% identical to the rat protein. The 13 coding exons of CACNB4
      span >55 kb of genomic DNA. Human cerebellar RNA contains one major CACNB4
      transcript that is 9 kb in length. Expression of CACNB4 was detected in
      cerebellum, kidney, testis, retina, lymphoblasts, and circulating lymphocytes.
      Retinal transcripts were localized by in situ hybridization to ganglion cells and
      the inner nuclear layer. Analysis of the GeneBridge 4 radiation hybrid mapping
      panel localized CACNB4 to position 791 cR on human chromosome 2, in a conserved
      linkage group on human 2q22-q31 and mouse chromosome 2. We localized CACNB4 to
      the 1.3-Mb YAC clone 952F10 in Whitehead contig WC861, along with the polymorphic
      markers D2S2236 and D2S2299. The chromosomal linkage of three of the four beta
      subunit genes to homeobox gene clusters associates the evolutionary origin of the
      beta gene family with the events that generated the four HOX clusters early in
      vertebrate evolution.

PMID- 9628819
TI  - The structures of the mouse and human urocortin genes (Ucn and UCN).
AB  - The mouse and human urocortin genes (Ucn and UCN, respectively) have been
      isolated, characterized, and found to have very similar structures. Each has two
      exons, and the entire coding region is located in the second exon, as is the case
      for the gene of the related peptide, corticotropin-releasing factor. Several
      putative transcription factor-binding sites were identified in each of the
      urocortin promoters, including a TATA box, a cyclic AMP response element (CRE),
      GATA-binding sites, and a C/EBP-binding site as well as a Brn-2-binding site(s).
      Sequence analyses of the mouse and human genes also revealed the presence of a
      previously identified gene, Mpv17, in the 5' region upstream of the urocortin
      gene. Functional studies following transient transfection of urocortin reporter
      plasmids in PC12 cells revealed that the urocortin promoter is controlled by both
      positive and negative elements; the CRE is important for basal activity as well
      as responsiveness to forskolin stimulation.

PMID- 9628820
TI  - The human homologue of the Drosophila tailless gene (TLX): characterization and
      mapping to a region of common deletion in human lymphoid leukemia on chromosome
      6q21.
AB  - Deletion of the long arm of chromosome 6 (6q) is one of the most common
      chromosomal abnormalities in human hematological malignancies. Two distinct
      regions of minimal deletion have been identified by loss of heterozygosity
      studies at 6q25 to 6q27 (RMD-1) and at 6q21 to 6q23 (RMD-2), suggesting the
      presence of one or more tumor suppressor genes. We have cloned sequences within
      RMD-2 and screened for novel genes using a combination of direct sequencing, cDNA
      library screening, and exon trapping. Sequences generated from a cosmid fragment,
      mapping within RMD-2, showed homology to the Drosophila tailless gene (tll). The
      human homologue of the Drosophila tailless gene (human tlx; MGMW-approved symbol,
      TLX) was subsequently cloned from a fetal brain cDNA library. The gene is a
      member of the steroid nuclear receptor superfamily and is homologous to tll genes
      from other species that are involved in brain development. TLX is predominately
      expressed in the brain and maps to RMD-2 at 6q21 between DNA markers FYN and
      D6S447, in a YAC clone that also contains marker D6S246. The contributions of
      this gene to human B-cell leukemia and to brain development are unknown at
      present.

PMID- 9628821
TI  - Identification of sequence-tagged transcripts differentially expressed within the
      human hematopoietic hierarchy.
AB  - Hematopoiesis is regulated by a complex gene expression program. To gain further
      insight into the molecular mechanisms underlying this process in humans, we
      sampled the transcriptional activity of the CD34+ hematopoietic progenitor line
      KG1a by single-pass sequencing the 5' ends of 1018 clones from a unidirectional
      cDNA library. Searches of public databases with the resulting expressed sequence
      tags (ESTs) identified 101 clones that showed no sequence similarity to any of
      the existing entries and that were therefore considered to derive from previously
      undescribed genes. Of the remaining 917 ESTs, 553 (a total of 485 distinct
      transcripts) corresponded to known genes. A further 279 KG1a ESTs matched or
      exhibited sequence similarity to ESTs or genomic sequences from humans and other
      species. Among the latter were putative human orthologs of developmental and cell
      cycle control genes from Caenorhabditis elegans, Drosophila, and yeast, as well
      as genes whose predicted amino acid sequences showed similarity to mammalian
      transcription factors. Hybridization of selected novel KG1a ESTs to globally
      amplified cDNAs prepared from single primary human hematopoietic precursors and
      homogeneous populations of terminally maturing hematopoietic cells revealed
      transcripts that are expressed preferentially at a specific stage or in a
      particular lineage within the hematopoietic hierarchy. Thus, included in the KG1a
      EST dataset are candidates for new human genes that may play roles in
      hematopoietic differentiative progression and lineage commitment.

PMID- 9628823
TI  - Cloning, characterization, and mapping of the mouse homeobox gene Hmx1.
AB  - Homeobox-containing genes play an important role in development, including
      positional specification of the body plan and organogenesis. We previously
      isolated the human HMX1 (H6) gene, a novel homeobox-containing gene of the HMX
      family, from a human embryonic craniofacial cDNA library. The closely related
      mouse genes Hmx3 (Nkx5.1) and Hmx2 (Nkx5.2) are in the same class as the HMX1
      gene and are expressed in the craniofacial region of the developing embryo. To
      provide a resource for further characterization of the human HMX1 gene, we
      isolated the mouse Hmx1 genomic clone. We show here the mouse Hmx1 genomic
      sequence, its gene mapping, and its expression pattern in the developing mouse
      embryo. Evidence is presented showing that the three known Hmx genes in the mouse
      likely play complementary roles in the development of the second arch, retina,
      sympathetic nerve ganglia, and cranial neural ganglia. Hmx1 may play an important
      role in the development of craniofacial structures and may interact with Hoxa-2
      and Dlx-2 in the second branchial arch.

PMID- 9628822
TI  - Isolation of human promoter regions by Alu repeat consensus-based polymerase
      chain reaction.
AB  - Knowledge of the promoter structure is critical for an understanding of the
      regulation of genes. We demonstrate by analysis of 405 human genes that human
      promoter regions are flanked by upstream Alu repeat elements, typically at a
      distance of 0.5-5 kb from their protein-coding areas. We identified common Alu
      repeat consensus sequences (ARC) among the different members of the Alu
      subfamilies that can be used as universal anchor sites for polymerase chain
      reaction (PCR) amplification. Utilizing ARC-specific primers and oligonucleotides
      specific for the 5' end of a selected target gene, we show that sequences
      spanning unknown human gene promoter regions can be directly amplified by PCR
      from genomic DNA. This novel technique, termed ARC-PCR, allowed us to
      characterize the proximal promoters of the human LTA4 hydrolase and SPARC genes,
      each within 1 day.

PMID- 9628824
TI  - Molecular cloning and characterization of the human p44 mitogen-activated protein
      kinase gene.
AB  - The complete genomic structure of the human p44(mapk) gene (HMGW-approved symbol
      PRKM3) has been determined. The gene covers 9 kb and is composed of nine exons
      and eight introns. This structure is identical to the previously reported mouse
      p44(mapk) gene, indicating a high degree of evolutionary conservation. A sequence
      differing by one nucleotide from the consensus TATA box is present 132 positions
      upstream of the main transcription initiation point. This point has been located
      415 nucleotides upstream of the translation initiation codon ATG and perfectly
      meets the consensus criteria for an initiator element (Inr). Multiple consensus
      sequences for factors that regulate either basal transcription or gene expression
      during cell differentiation and proliferation can be found in the putative
      promoter region. Some of them, such as several G/C boxes located downstream from
      the transcription initiation point, are also present in the homologous mouse
      gene, where they were shown to be functional.

PMID- 9628825
TI  - An alternative first exon in the distal end of the erythroid ankyrin gene leads
      to production of a small isoform containing an NH2-terminal membrane anchor.
AB  - Mouse erythroid ankyrin is encoded by the Ank1 gene on Chromosome 8. The best
      studied isoform is 210 kDa and contains three large functional domains. We have
      recently reported a small Ank1 isoform (relative mobility 25 kDa) that localizes
      to the M and Z lines in skeletal muscle. Analyses of cDNA and genomic clones show
      that three transcripts of 3.5, 2.0, and 1.6 kb code for this protein. The
      different transcript sizes are due to their 3'-untranslated regions. They are
      encoded by a new first exon located in intron 39 of the Ank1 gene and three
      previously described Ank1 exons (40, 41, and 42). The 5'-flanking region contains
      a putative muscle-specific promoter. The sequence of the first 72 amino acids is
      novel and is predicted to form a transmembrane helix at the NH2-terminus.
      Functional testing of the putative transmembrane segment indicates that it acts
      as a membrane anchor, suggesting that the new Ank1 isoform may play an important
      role in organizing the contractile apparatus within the cell.

PMID- 9628826
TI  - Cystic fibrosis Delta F508 heterozygotes, smoking, and reproduction: studies of
      9141 individuals from a general population sample.
AB  - Cystic fibrosis is the most common fatal autosomal recessive disease affecting
      Caucasian populations. It remains a puzzle how this disease is maintained at such
      a remarkably high incidence, however, it could be due to a reproductive advantage
      in cystic fibrosis heterozygotes. We tested this hypothesis. An adult Danish
      general population sample of 9141 individuals was screened for cystic fibrosis
      DeltaF508 heterozygotes; 250 carriers of this mutation were identified (2.7%). In
      the total sample DeltaF508 heterozygotes did not have more children than
      noncarriers; however, smoking interacted with genotype in predicting number of
      children (ANOVA: P < 0.001). Among nonsmokers, heterozygotes had more children
      than noncarriers (Wilcoxon: P = 0.03). Among smokers, the opposite was found:
      heterozygotes had fewer children than noncarriers (Wilcoxon: P = 0. 001). These
      findings remained significant after allowing for gender and the potential
      confounders of age, income, and education. Finally, after allowing for these
      covariates, number of children in DeltaF508 heterozygotes decreased with
      increasing extent of smoking (trend test: P = 0.003), while the opposite was true
      for noncarriers (trend test: P < 0.001). In conclusion, overall these results do
      not support a reproductive advantage for cystic fibrosis DeltaF508 heterozygotes.
      However, the data cannot totally exclude the possibility that nonsmoking
      DeltaF508 heterozygotes experience a reproductive advantage while smoking
      DeltaF508 heterozygotes experience the opposite, a reproductive disadvantage.
      Accordingly, the data suggest a previously undocumented role of smoking on
      fecundity among cystic fibrosis heterozygotes.

PMID- 9628827
TI  - Cloning, chromosomal mapping, and regulatory properties of the human type 9
      adenylyl cyclase (ADCY9).
AB  - The type 9 adenylyl cyclase (AC9) is a widely distributed adenylyl cyclase that
      was originally cloned from a mouse cDNA library. Here we report the cloning,
      chromosomal mapping, and regulatory properties of human AC9 (HGMW-approved symbol
      ADCY9). Although the human AC9 sequence shows 86% homology with mouse AC9,
      divergence at the C2a/C2b junction results in an alternative C2b amino acid
      sequence. In situ hybridization localized the human AC9 gene to both human and
      mouse chromosomes 16. AC9 mRNA is present in all tissues examined, with the
      highest levels found in skeletal muscle, heart, and brain. To characterize the
      regulatory properties of human AC9 in vivo, the enzyme was expressed in HEK-293
      cells. Human AC9 is stimulated by beta-adrenergic receptor activation but is
      insensitive to forskolin, Ca2+ and somatostatin. In contrast to mouse AC9, the
      activity of human AC9 is unaffected by inhibitors of calcineurin. These data
      emphasize the importance of determining the regulatory properties of human
      adenylyl cyclases.

PMID- 9628828
TI  - Chromosomal localization of the genes for human carboxypeptidase D (CPD) and the
      active 50-kilodalton subunit of human carboxypeptidase N (CPN1).
AB  - Human carboxypeptidase N is a 280-kDa tetrameric enzyme consisting of two 83-kDa
      regulatory subunits and two catalytic 50-kDa subunits. The 83-kDa subunit is a
      member of the leucine-rich repeat family of proteins and has been localized to
      chromosome 8p22-p23. The 50-kDa subunit is a member of the regulatory B-type
      carboxypeptidase family, which includes carboxypeptidases M, E/H, AEBP1, and a
      newly described member, carboxypeptidase D, which has three tandem active site
      domains. The human genes for carboxypeptidase D (HGMW-approved symbol CPD) and
      the 50-kDa subunit of carboxypeptidase N (HGMW-approved symbol CPN1) were
      localized to chromosomes 17 and 10, respectively, using the polymerase chain
      reaction with gene-specific primers and DNAs derived from somatic cell hybrids.
      The carboxypeptidase D gene was further localized to the centromeric region
      17p11.1-q11.1/11.2 by use of a regional mapping panel derived from somatic cell
      hybrids containing different portions of chromosome 17.

PMID- 9628829
TI  - Physical mapping of the evolutionary boundary between human chromosomes 21 and 22
      on mouse chromosome 10.
AB  - Adjacent regions of mouse Chromosome 10 (MMU10) show conserved synteny with human
      chromosome 22 (HSA22) and the telomeric region of HSA21. Physical mapping on
      MMU10 using YAC fragmentation and PAC contig analyses demonstrates that Prmt2 has
      a position consistent with its human homolog, HRMT1L1, being telomeric to S100B
      on HSA21. This result establishes Prmt2 as the new proximal boundary of the
      region of conserved synteny between MMU10 and HSA21 and predicts that it is the
      most telomeric gene known on HSA21. Physical mapping refines the positions and
      order of HSA22 homologs Mmp11, Mif, and Ddt, demonstrates the orientation of
      S100b on the mouse chromosome, and localizes the junction of conserved synteny
      between HSA21 and HSA22 on MMU10. Comparative mapping in this region is important
      for defining gene structure and dosage imbalance in Down syndrome (DS), for
      developing animal models of DS, and for understanding processes of chromosome
      evolution.

PMID- 9628830
TI  - Chromosomal localization of the human smoothened gene (SMOH) to 7q32. 3 by
      fluorescence in situ hybridization and radiation hybrid mapping.

PMID- 9628831
TI  - Assignment of the membrane-bound human aminopeptidase P gene (XPNPEP2) to
      chromosome Xq25.

PMID- 9628832
TI  - Cloning and molecular characterization of a cross-homologous zinc finger locus
      ZNF204.

PMID- 9628833
TI  - Mapping of Nakano cataract gene nct on mouse chromosome 16.

PMID- 9628834
TI  - Hypothesis: one cause of polydactyly.
AB  - The strongly male-biased sex ratios of probands with polydactyly and of their
      unaffected sibs suggests that abnormal maternal hormone levels may be involved in
      this malformation. This suspicion is supported by data relating polydactyly to
      maternal age and race. High maternal testosterone seems capable of explaining the
      (admittedly limited) epidemiological data on polydactyly. If this were so, one
      may predict that offspring risk would be higher in respect of affected mothers
      than affected fathers.

PMID- 9628835
TI  - Parental Optimism and Progeny Choice: When is Screening for Offspring Quality
      Affordable.
AB  - Three general classes of fitness incentives have been proposed for parental
      overproduction of offspring: (1) tracking environmental variation; (2)
      developmental facilitation; and (3) replacements for failed or defective members
      of the core brood. In one version of this last category, called the progeny
      choice hypothesis, parents are seen as creating an enlarged array of offspring
      from which a genetically superior subset is chosen for full investment. In the
      selection process, parents may eliminate the victims either through personal
      effort (filial infanticide) or by proxy (by allowing or even encouraging fatal
      sibling rivalry). Because the culling process is non-random, it can elevate
      average offspring quality. Progeny choice, however, is only cost-effective if the
      expenses of early overproduction (including elevated levels of sibling
      competition) do not outweigh the eventual upgrade in offspring quality. A fair
      competition within the offspring "arena" offers the greatest potential for
      discriminating on the basis of intrinsic quality, but may be overwhelmed by high
      costs of sibling rivalry. Conversely, while parentally managed competition
      (conferring handicaps to some and advantages to others) can discount those
      rivalry costs, it simultaneously diminishes the system's capacity for
      distinguishing good offspring from bad. Ceteris paribus, one would expect to find
      progeny choice mechanisms in species with cheap sibling rivalry, large cohorts of
      evenly matched offspring, and exaggerated variation in offspring genetic quality.
      Conversely, this class of incentives of parental overproduction seems least
      suited to taxa in which parents dole out marked advantages or handicaps to
      various concurrent offspring (e.g. asynchronously hatching birds).Copyright 1998
      Academic Press Limited

PMID- 9628836
TI  - Resonance effect in self-renewing tissues.
AB  - It was predicted previously that a depletion of cell population depends extremely
      on the period of periodic phase-specific killing of cells and at periods near the
      integer multiple of the mean cell-cycle time there is a considerable reduction in
      treatment-induced decrease of cell-population size (resonance effect). This paper
      is devoted to theoretical and experimental analysis of the resonance effect in
      self-renewing tissues. The main biological assumptions underlying the idea of the
      resonance effect are discussed and then reformulated in terms of a mathematical
      model. The model describes kinetics of cell populations under periodic treatment
      by high doses of a phase-specific cytotoxic agent with blocking effect. The
      dependence of cell survival on cell-cycle parameters and parameters of treatment
      is studied and the results are presented in a suitable form for experimental
      testing and practical usage. The obtained results give a theoretical basis for
      using the resonance effect in a self-renewing tissue control study and estimation
      of cell-cycle parameters of various cells including morphologically
      unrecognizable ones. The quantitative comparison of the theoretical predictions
      with experimental data obtained for mice spleen colony forming units (CFUs),
      cells of mice small intestine epithelium as well L1210 leukemic cells is carried
      out. The excellent agreement between theoretical and experimental results is
      demonstrated and the estimations of cycle parameters of CFUs, cryptogenic and
      transit cells of mice intestine epithelium are obtained. Biological consequences
      of the obtained results are discussed and the new hypothesis relative to self
      renewing tissue proliferative control is put forward.

PMID- 9628837
TI  - Induced potential model for muscular contraction mechanism, including two
      attached states of myosin head.
AB  - The model for myosin head motion along an actin filament as proposed by Mitsui &
      Chiba [(1996). J. theor. Biol. 182, 147-159] is here modified so that it can
      explain the isometric tension and isotonic velocity transients having the same
      parameter values as the stationary filament sliding. The modified model differs
      in that a myosin head forms a complex with two actin molecules in an actin
      filament and has two attached states in the complex instead of three. Thus an
      incremental step in the myosin head motion is equal to the F-actin monomer repeat
      (5.46 nm). Muscle properties concerning the stationary filament sliding are
      calculated with new parameters in a manner similar to that of Mitsui-Chiba, with
      the results being qualitatively similar to theirs. In studying the transient
      phenomena, a quantitative expression is given for the potential energy of the
      myosin head in the complex, and two rate constants are applied to the kinetics of
      the head. The time course of tension recovery after a quick length change is
      determined by calculating the statistical distribution of the head in the two
      attached states, which conforms to experimental observations by Ford et al.
      [(1977). J. Physiol. 269, 441-515]. The tension variations T1/T0 and T2/T0
      calculated with parameters determined from the analysis of stationary filament
      slidings are in fairly good agreement with the experimental data by Ford et al.
      The model suggests that a large fluctuation exists in the relative position
      between the actin and myosin filaments even when the load on a muscle is kept
      constant. Taking this fluctuation into account explains the characteristics of
      the isotonic velocity transient observed by Civan & Podolsky.

PMID- 9628838
TI  - The indirect verification of minimal two-generator model of homeostatic drinking
      by complexity examination.
AB  - In the course of previous examinations, it has been suggested that minimally two
      lick pattern generators have to take part in the formation of temporal patterns
      of homeostatic drinking. The drinking pattern of five rats was investigated,
      subsequently analysed and compared to simulated data. As the interaction of the
      two generators changes by the progress of satiation, the dynamics of drinking
      have to change too. In this experiment we demonstrated this nonlinear dynamical
      change by the examination of algorithmic complexity which reflects the nature of
      motivational changes and that the proportion of the change of complexity is in
      harmony with our model of homeostatic drinking.

PMID- 9628840
TI  - Nonlinear Variation in Simulated Complex Pattern Development.
AB  - Simulated spore walls manufactured from colloidal polystyrene latex, cyclohexane
      and water demonstrate a range of structure comparable with that occurring within
      the walls of Selaginella megaspores. Initial investigation of the relationship
      between the initiation parameters of the self-assembling simulation and its
      ultimate structure imply a nonlinear relationship. It is suggested that such self
      assembly processes result in structure that cannot be directly mapped onto an
      equivalent genetic coding and that phylogenetic analyses based on self-assembled
      structure may differ in its conclusions from that based on DNA
      sequences.Copyright 1998 Academic Press Limited

PMID- 9628839
TI  - Analysis of models involving enzymatic activities for the occurrence of C-->T
      transition mutations during repeat-induced point mutation (RIP) in Neurospora
      crassa.
AB  - The phenomenon of repeat-induced point mutation (RIP), acting during the sexual
      phase of the model eukaryote Neurospora crassa, is considered to study the
      putative in vivo relationships existing between cellular levels of S
      adenosylmethionine (SAM), cytosine methylation and the occurrence of C-->T
      transition mutations. We analyse the kinetic behaviour of the different enzymatic
      models proposed to explain the underlying mutagenic mechanisms of RIP. The
      dependence of the mutation rate on the cellular levels of the methyl group donor
      SAM was evaluated for the models of mutation catalysed by a DNA-cytosine
      deaminase, a DNA-(5-methylcytosine) deaminase, a DNA-(5-cytosine)
      methyltransferase, and for a model combining the activities of the last two
      enzymes. We propose that these models can be distinguished by studying the
      dependence of RIP on intracellular SAM levels.

PMID- 9628841
TI  - Mathematical analysis of antiretroviral therapy aimed at HIV-1 eradication or
      maintenance of low viral loads.
AB  - Motivated by the ability of combinations of antiretroviral agents to sustain
      viral suppression in HIV-1-infected individuals, we analyse the transient and
      steady-state behavior of a mathematical model of HIV-1 dynamics in vivo in order
      to predict whether these drug regimens can eradicate HIV-1 or maintain viral
      loads at low levels. The model incorporates two cell types (CD4+ T cells and a
      long-lived pool of cells), two strains of virus (drug-sensitive wild type and
      drug-resistant mutant) and two types of antiretroviral agents (reverse
      transcriptase and protease inhibitors). The transient behavior of the cells and
      virus and the eventual eradication of the virus are determined primarily by the
      strength of the combination therapy against the mutant strain and the maximum
      achievable increase in the uninfected CD4+ T cell concentration. We also predict,
      if the parameters of the model remain constant during therapy, that less
      intensive maintenance regimens will be unable to maintain low viral loads for
      extensive periods of time. However, if the reduction in viral load produced by
      therapy reduces the state of activation of the immune system, the number of cells
      susceptible for HIV-1 infection may decrease even though total CD4+ T cells
      increase. Our model predicts that if this occurs strong inductive therapy that
      reduces viral load followed by weaker maintenance regimes may succeed.

PMID- 9628842
TI  - Dynamics of cytonuclear disequilibria in subdivided populations.
AB  - The purpose of this report is to understand the effects of hybrid zone
      architecture and genetic drift on cytonuclear genotypic disequilibria. We also
      study the exact dynamics of the expected values of the cytonuclear genotypic
      disequilibria for both the homozygotes and heterozygotes in a finite population
      containing reproductively isolated subpopulations under random drift alone and
      random drift along with mutation, respectively. We study the dynamics of the
      between-population component of the disequilibrium for the homozygotes. The
      dynamics of the variances of these disequilibria under the random drift model are
      studied by Monte Carlo simulations. The asymptotic formulas for both the
      expectations and variances are obtained. The results are contrasted with those
      for a single undivided population and their biological significances are
      discussed. Approximate normality of the disequilibria measures are also
      demonstrated by Monte Carlo simulations.

PMID- 9628843
TI  - Hypotheses on mammalian sex ratio variation at birth.
AB  - Some comments are made on two hypotheses on the variation of mammalian sex ratios
      (proportions male) at birth viz. Krackow's developmental asynchrony hypothesis
      and my parental hormone hypothesis. It seems not unfair to characterise his
      hypothesis as functioning to support the conventional Mendelian paradigm. In
      contrast, if my hypothesis were true, some adjustment would have to be made to
      that paradigm. Here I suggest further ways of testing Krackow's hypothesis
      experimentally. In contrast, my own hypothesis seems to lend itself also to
      testing by epidemiological methods; here it is suggested that the offspring sex
      ratios of several specified categories of ill men should be low.

PMID- 9628844
TI  - Predicting temporal fluctuations in an intracellular signalling pathway.
AB  - We used a newly developed stochastic-based program to predict the fluctuations in
      numbers of molecules in a chemotactic signalling pathway of coliform bacteria.
      Specifically, we examined temporal changes in molecules of CheYp, a cytoplasmic
      protein known to influence the direction of rotation of the flagellar motor.
      Signalling molecules in the vicinity of a flagellar motor were represented as
      individual software objects interacting according to probabilities derived from
      experimentally-observed concentrations rate constants. The simulated CheYp
      molecules were found to undergo random fluctuations in number about an average
      corresponding to the deterministically calculated concentration. Both the
      relative amplitude of the fluctuations, as a proportion of the total number of
      molecules, and their average duration, increased as the simulated volume was
      reduced. In a simulation corresponding to 10% of the volume of a bacterium, the
      average duration of fluctuations was found to be 80.7 ms, which is much shorter
      than the observed alternations between clockwise and counter clockwise rotations
      of tethered bacteria (typically 2.6 s). Our results are therefore not in
      agreement with a simple threshold-crossing model for motor switching. However, it
      is possible to filter the CheYp fluctuations to produce temporal distributions
      closer to the observed swimming behaviour and we discuss the possible
      implications for the control of motor rotation.

PMID- 9628845
TI  - Diffusion and Direct Signaling Models are Numerically Equivalent.
AB  - Copyright 1998 Academic Press Limited

PMID- 9628847
TI  - Commentary: Involvement of Amino Acid Residues 423-429 of Human Protein S in
      Binding to C4b-Binding Protein.
AB  - Copyright

PMID- 9628846
TI  - Involvement of amino acid residues 423-429 of human protein S in binding to C4b
      binding protein.
AB  - Human protein S binds to C4b-binding protein (C4BP) both in plasma and in a
      system using purified proteins. Amino acid residues 420-434 of the first
      disulfide loop of the sex hormone binding globulinlike domain of protein S are
      involved in the interaction of protein S with C4BP. To define the involvement of
      specific polar amino acids within residues 420-434, we studied in parallel
      synthetic protein S peptides and recombinant protein S variants containing the
      same amino acid replacements, K423E, E424K, Q427E and K429E. Synthetic peptide
      analogs of peptide PSP-420 (residues 420-434) were assayed for binding C4BP and
      as inhibitors of complex formation. The PSP-420 peptide and the analogous peptide
      with the substitution E424K, but not the peptides containing the substitutions
      K423E and K429E, were able to bind C4BP. Recombinant proteins with mutations of
      K423E, Q427E and K429E showed reduced affinity for C4BP compared to plasma
      protein S, recombinant wild type protein S, or E424K-protein S. These results
      suggest that Lys-423, Gln-427 and Lys-429 of protein S are important for normal
      binding to C4BP. The anti-protein S monoclonal antibody LJ-56, raised against
      peptide PSP-420, recognizes only free protein S and inhibits complex formation
      with C4BP. Antibody LJ-56 recognized the E424K and Q427E peptides but not the
      K423E or K429E peptides. Similarly, the E424K and Q427E protein S mutants were
      recognized by LJ-56, whereas the K423E and K429E protein S mutants were not
      recognized. This suggests that both in the peptide PSP-420 and in protein S, Lys
      423 and Lys-429 significantly contribute to binding to antibody LJ-56. These
      results demonstrate that protein S residues 423, 427 and 429, but not residue
      424, are involved in binding to both the antibody LJ-56 and to C4BP. When
      peptides PSP 420 and SL-6 (residues 447-460) with carboxyterminal amide or
      carboxylate moieties were compared to their ability to inhibit C4BP-protein S
      complexation, PSP-420-amide was the most potent. This finding together with the
      other results described here supports the hypothesis that the residues 420 and
      434 in protein S provides a major binding site for C4BP.

PMID- 9628848
TI  - Arginine butyrate-induced susceptibility to ganciclovir in an Epstein-Barr-virus
      associated lymphoma.
AB  - Lymphoproliferative disorders associated with Epstein-Barr virus (EBV) infections
      can occur in the setting of immunosuppression. In some patients, the
      lymphoproliferative disorder can resemble an aggressive monoclonal non-Hodgkins
      lymphoma (NHL). These NHL are poorly responsive to conventional therapy.
      Similarly, antiviral therapy with synthetic nucleosides such as ganciclovir are
      ineffective because the genes that render the virus susceptible to therapy are
      not expressed in EBV+ lymphomas. Using a cell line derived from a lung transplant
      recipient with an EBV+ immunoblastic NHL, we studied the ability of arginine
      butyrate to induce the expression of EBV thymidine kinase. Arginine butyrate was
      not only effective in inducing EBV thymidine kinase transcription, but also acted
      synergistically with the antiviral agent ganciclovir to inhibit cell
      proliferation and decrease cell viability. Based on these findings, the patient
      from whom the cell line was derived was treated with arginine
      butyrate/ganciclovir as well as conventional cytotoxic chemotherapy. No
      additional toxicity was observed with the arginine butyrate/ganciclovir therapy.
      Histologic examination of the tumor showed substantial necrosis. These
      observations suggest the feasibility of arginine butyrate induction of
      ganciclovir susceptibility in patients with EBV-associated lymphomas.

PMID- 9628850
TI  - Commentary: Involvement of H-ras in Erythroid Differentiation of TF1 and Human
      Umbilical Cord Blood CD34+++ Cells.
AB  - Copyright

PMID- 9628849
TI  - Involvement of H-ras in erythroid differentiation of TF1 and human umbilical cord
      blood CD34 cells.
AB  - To investigate the role of the ras gene in erythroid differentiation, a human
      erythroleukemic cell line, TF1, was transduced with a selectable retroviral
      vector carrying a mammalian wild type H-ras gene or a cytoplasmic dominant
      negative RAS1 gene. Transduction of TF1 cells with the wild type H-ras gene
      resulted in changes of cell types and up-regulation of erythroid-specific gene
      expression similar to that seen in differentiating erythroid cells. The number of
      red blood cell containing colonies derived from TF1 cells transduced with wild
      type H-ras cDNA was significantly increased and the cells in the colonies were
      more hemoglobinized as estimated by a deeper red color compared to those colony
      cells from mock or dominant negative RAS1 gene transduced TF1 cells, suggesting
      increased erythroid differentiation of TF1 cells after transduction of wild type
      H-ras in vitro. The mRNA levels of beta- and gamma-, but not alpha-, globin genes
      were significantly higher in H-ras transduced TF1 cells than those in TF1 cells
      transduced with mock or dominant negative RAS1 gene. Moreover, a 4kb pre-mRNA of
      the Erythropoietin receptor (EpoR) was highly expressed only in H-ras transduced
      TF1 cells. Additionally, human umbilical cord blood (CB) CD34 cells which are
      highly enriched for hematopoietic stem/progenitor cells were transduced with the
      same retroviral vectors to evaluate in normal primary cells the activities of H
      ras in erythroid differentiation. Increased numbers of erythroid cell containing
      colonies (BFU-E and CFU-GEMM) were observed in CD34 cells transduced with the H
      ras cDNA, compared to that from mock transduced cells. These data suggest a
      possible role for ras in erythroid differentiation.

PMID- 9628851
TI  - A positive effect of p21cip1/waf1 in the colony formation from murine myeloid
      progenitor cells as assessed by retroviral-mediated gene transfer.
AB  - p21cip1/waf1 is a cyclin dependent kinase inhibitor. We have previously reported
      stimulation of p21cip1/waf1 by steel factor and GM-CSF in a factor dependent cell
      line and of p21cip1/waf1 involvement in hematopoiesis in vivo in p21cip1/waf1
      gene knockout (-/-) mice. To further assess a role for increased p21cip1/waf1 in
      hematopoietic progenitor cells, we developed the retroviral vector L(p21cip1)SN
      to transcriptionally regulate p21cip1/waf1 from the Mo-MLV LTR. L(p21cip1)SN and
      the control vector LXSN were used to transduce murine bone marrow progenitor
      cells from p21cip1/waf1 (-/-) and littermate control (+/+) mice, as well as from
      other mouse strains. Hematopoietic colony formation by transduced cells was
      assessed in semi-solid culture medium with multiple growth factors. Myeloid
      colony formation by bone marrow cells from p21cip1/waf1 (-/-) mice was
      significantly lower than that by (+/+) mouse cells. Transduction of cells with
      LXSN had no effect on colony formation: however, (-/-) cells transduced with
      L(p21cip1)SN formed significantly greater numbers of colonies than either LXSN
      transduced (-/-) or (+/-) cells. Moreover, L(p21cip1)SN-transduced (+/+) cells
      formed significantly more colonies than LXSN-transduced (+/+) cells. Increased
      cloning efficiency of progenitors from normal strains of mice induced by
      L(p21cip1)SN compared to LXSN-transduced cells was seen whether unseparated or
      highly purified populations of Sca1+ Lin- marrow cells were used. Gene transfer
      of L(p21cip1)SN increased the size and number of cells per colony, as well as the
      number of colonies compared to LXSN gene transfer. No colonies grew from non
      transduced, LXSN-, or L(p21cip1)SN-transduced cells when no growth factors were
      added to the cultures. These results document the positive effect of p21cip1/waf1
      in the proliferation and/or differentiation of the murine myeloid progenitor
      cells that lead to colony formation.

PMID- 9628852
TI  - Ribonuclease inhibitor protein of human erythrocytes: characterization, loss of
      activity in response to oxidative stress, and association with Heinz bodies.
AB  - Significant amounts of ribonuclease inhibitor protein are present in human and
      rat erythrocytes, cells that are essentially devoid of ribonuclease or functional
      RNA. The protein from human erythrocytes is indistinguishable from human
      placental ribonuclease inhibitor protein by immunological and biochemical
      criteria. Each inhibitor forms an equimolar complex with bovine pancreatic
      ribonuclease A and is inactivated by treatment with the sulfhydryl reagent p
      (hydroxymercuri)benzoate. Amino acid composition and several cycles of amino acid
      sequence analysis also showed apparent identify of the erythrocyte and placental
      proteins. We calculate a level of 1.5-3.5 x 10(4) molecules of active inhibitor
      per erythrocyte, most or all of which occurs in an uncomplexed form since
      inactivation of the inhibitor revealed barely detectable levels of RNase
      activity. Immunogold localization showed a high level of labeling and a uniform
      distribution of gold particles in the cytoplasm of erythrocytes, while little
      inhibitor activity was found in association with isolated red blood cell
      membranes. Oxidative stress on isolated red cells resulted in a decrease in the
      level of reduced glutathione and a gradual and irreversible loss of inhibitor
      activity; inhibitor disappeared from the cytosol and became associated with
      nascent Heinz bodies. We suggest a role for this protein in the metabolism and
      aging process of the erythrocyte.

PMID- 9628859
TI  - Crystal structures of Toxoplasma gondii uracil phosphoribosyltransferase reveal
      the atomic basis of pyrimidine discrimination and prodrug binding.
AB  - Uracil phosphoribosyltransferase (UPRTase) catalyzes the transfer of a ribosyl
      phosphate group from alpha-D-5-phosphoribosyl-1-pyrophosphate to the N1 nitrogen
      of uracil. The UPRTase from the opportunistic pathogen Toxoplasma gondii is a
      rational target for antiparasitic drug design. To aid in structure-based drug
      design studies against toxoplasmosis, the crystal structures of the T.gondii apo
      UPRTase (1.93 A resolution), the UPRTase bound to its substrate, uracil (2.2 A
      resolution), its product, UMP (2.5 A resolution), and the prodrug, 5-fluorouracil
      (2.3 A resolution), have been determined. These structures reveal that UPRTase
      recognizes uracil through polypeptide backbone hydrogen bonds to the uracil
      exocyclic O2 and endocyclic N3 atoms and a backbone-water-exocyclic O4 oxygen
      hydrogen bond. This stereochemical arrangement and the architecture of the uracil
      binding pocket reveal why cytosine and pyrimidines with exocyclic substituents at
      ring position 5 larger than fluorine, including thymine, cannot bind to the
      enzyme. Strikingly, the T. gondii UPRTase contains a 22 residue insertion within
      the conserved PRTase fold that forms an extended antiparallel beta-arm. Leu92, at
      the tip of this arm, functions to cap the active site of its dimer mate, thereby
      inhibiting the escape of the substrate-binding water molecule.

PMID- 9628860
TI  - Interaction of polyomavirus internal protein VP2 with the major capsid protein
      VP1 and implications for participation of VP2 in viral entry.
AB  - A complex of the polyomavirus internal protein VP2/VP3 with the pentameric major
      capsid protein VP1 has been prepared by co-expression in Escherichia coli. A C
      terminal segment of VP2/VP3 is required for tight association, and a crystal
      structure of this segment, complexed with a VP1 pentamer, has been determined at
      2.2 A resolution. The structure shows specific contacts between a single copy of
      the internal protein and a pentamer of VP1. These interactions were not detected
      in the previously described structure of the virion, but the location of VP2 in
      the recombinant complex is consistent with features in the virion electron
      density map. The C-terminus of VP2/VP3 inserts in an unusual, hairpin-like manner
      into the axial cavity of the VP1 pentamer, where it is anchored strongly by
      hydrophobic interactions. The remainder of the internal protein appears to have
      significant flexibility. This structure restricts possible models for exposure of
      the internal proteins during viral entry.

PMID- 9628861
TI  - UBPY: a growth-regulated human ubiquitin isopeptidase.
AB  - The ubiquitin pathway has been implicated in the regulation of the abundance of
      proteins that control cell growth and proliferation. We have identified and
      characterized a novel human ubiquitin isopeptidase, UBPY, which both as a
      recombinant protein and upon immunoprecipitation from cell extracts is able to
      cleave linear or isopeptide-linked ubiquitin chains. UBPY accumulates upon growth
      stimulation of starved human fibroblasts, and its levels decrease in response to
      growth arrest induced by cell-cell contact. Inhibition of UBPY accumulation by
      antisense plasmid microinjection prevents fibroblasts from entering S-phase in
      response to serum stimulation. By increasing or decreasing the cellular abundance
      of UBPY or by overexpressing a catalytic site mutant, we detect substantial
      changes in the total pattern of protein ubiquitination, which correlate
      stringently with cell proliferation. Our results suggest that UBPY plays a role
      in regulating the overall function of the ubiquitin-proteasome pathway. Affecting
      the function of a specific UBP in vivo could provide novel tools for controlling
      mammalian cell proliferation.

PMID- 9628862
TI  - Role of the proteasome in membrane extraction of a short-lived ER-transmembrane
      protein.
AB  - Selective degradation of proteins at the endoplasmic reticulum (ER-associated
      degradation) is thought to proceed largely via the cytosolic ubiquitin-proteasome
      pathway. Recent data have indicated that the dislocation of short-lived integral
      membrane proteins to the cytosolic proteolytic system may require components of
      the Sec61 translocon. Here we show that the proteasome itself can participate in
      the extraction of an ER-membrane protein from the lipid bilayer. In yeast mutants
      expressing functionally attenuated proteasomes, degradation of a short-lived
      doubly membrane-spanning protein proceeds rapidly through the N-terminal
      cytosolic domain of the substrate, but slows down considerably when continued
      degradation of the molecule requires membrane extraction. Thus, proteasomes
      engaged in ER degradation can directly process transmembrane proteins through a
      mechanism in which the dislocation of the substrate and its proteolysis are
      coupled. We therefore propose that the retrograde transport of short-lived
      substrates may be driven through the activity of the proteasome.

PMID- 9628863
TI  - Mapping the interaction between GRASP65 and GM130, components of a protein
      complex involved in the stacking of Golgi cisternae.
AB  - The nature of the complex containing GRASP65, a membrane protein involved in
      establishing the stacked structure of the Golgi apparatus, and GM130, a putative
      Golgi matrix protein and vesicle docking receptor, was investigated. Gel
      filtration revealed that GRASP65 and GM130 interact in detergent extracts of
      Golgi membranes under both interphase and mitotic conditions, and that this
      complex can bind to the vesicle docking protein p115. Using in vitro translation
      and site-directed mutagenesis in conjunction with immunoprecipitation, the
      binding site for GRASP65 on GM130 was mapped to the sequence xxNDxxxIMVI-COOH at
      the C-terminus of GM130, a region known to be required for its localization to
      the Golgi apparatus. The same approach was used to show that the binding site for
      GM130 on GRASP65 maps to amino acids 189-201, a region conserved in the mammalian
      and yeast proteins and reminiscent of PDZ domains. Using green fluorescent
      protein (GFP)-tagged reporter constructs, it was shown that one essential
      function of the interaction between GRASP65 and GM130 is in the correct targeting
      of the two proteins to the Golgi apparatus.

PMID- 9628864
TI  - Vam7p, a vacuolar SNAP-25 homolog, is required for SNARE complex integrity and
      vacuole docking and fusion.
AB  - The vacuole v-t-SNARE complex is disassembled by Sec17p/alpha-SNAP and Sec18p/NSF
      prior to vacuole docking and fusion. We now report a functional characterization
      of the vacuolar SNARE Vam7p, a SNAP-25 homolog. Although Vam7p has no hydrophobic
      domains, it is tightly associated with the vacuolar membrane. Vam7p is a
      constituent of the vacuole SNARE complex and is released from this complex by the
      Sec17p/Sec18p/ATP-mediated priming of the vacuoles. Even in the absence of the
      vacuolar v-SNARE Nyv1p, a subcomplex which includes Vam7p and the t-SNARE Vam3p
      is preserved. Vam7p is necessary for the stability of the vacuolar SNARE complex,
      since vacuoles from mutants deleted in VAM7 do not have a Vam3p-Nyv1p complex.
      Furthermore, Vam7p alone, in the absence of Nyv1p and Vam3p, cannot mediate
      fusion with wild-type vacuoles, whereas vacuoles with only Nyv1p or Vam3p alone
      can fuse with wild-type vacuoles in the absence of the other two SNAREs. Thus,
      Vam7p is important for the stable assembly and efficient function of the vacuolar
      SNARE complex and maintenance of the vacuolar morphology. This functional
      characterization of Vam7p suggests a general role for SNAP-25 homologs, not only
      on the plasma membrane but along the secretory pathway.

PMID- 9628865
TI  - Chromogranin B (secretogranin I), a neuroendocrine-regulated secretory protein,
      is sorted to exocrine secretory granules in transgenic mice.
AB  - Chromogranin B (CgB, secretogranin I) is a secretory granule matrix protein
      expressed in a wide variety of endocrine cells and neurons. Here we generated
      transgenic mice expressing CgB under the control of the human cytomegalovirus
      promoter. Northern and immunoblot analyses, in situ hybridization and
      immunocytochemistry revealed that the exocrine pancreas was the tissue with the
      highest level of ectopic CgB expression. Upon subcellular fractionation of the
      exocrine pancreas, the distribution of CgB in the various fractions was
      indistinguishable from that of amylase, an endogenous constituent of zymogen
      granules. Immunogold electron microscopy of pancreatic acinar cells showed co
      localization of CgB with zymogens in Golgi cisternae, condensing
      vacuoles/immature granules and mature zymogen granules; the ratio of
      immunoreactivity of CgB to zymogens being highest in condensing vacuoles/immature
      granules. CgB isolated from zymogen granules of the pancreas of the transgenic
      mice aggregated in a mildly acidic (pH 5.5) milieu in vitro, suggesting that low
      pH-induced aggregation contributed to the observed concentration of CgB in
      condensing vacuoles. Our results show that a neuroendocrine-regulated secretory
      protein can be sorted to exocrine secretory granules in vivo, and imply that a
      key feature of CgB sorting in the trans-Golgi network of neuroendocrine cells,
      i.e. its aggregation-mediated concentration in the course of immature secretory
      granule formation, also occurs in exocrine cells although secretory protein
      sorting in these cells is thought to occur largely in the course of secretory
      granule maturation.

PMID- 9628866
TI  - Molecular determinants of KATP channel inhibition by ATP.
AB  - ATP-sensitive K+ (KATP) channels are both inhibited and activated by
      intracellular nucleotides, such as ATP and ADP. The inhibitory effects of
      nucleotides are mediated via the pore-forming subunit, Kir6.2, whereas the
      potentiatory effects are conferred by the sulfonylurea receptor subunit, SUR. The
      stimulatory action of Mg-nucleotides complicates analysis of nucleotide
      inhibition of Kir6. 2/SUR1 channels. We therefore used a truncated isoform of
      Kir6.2, that expresses ATP-sensitive channels in the absence of SUR1, to explore
      the mechanism of nucleotide inhibition. We found that Kir6.2 is highly selective
      for ATP, and that both the adenine moiety and the beta-phosphate contribute to
      specificity. We also identified several mutations that significantly reduce ATP
      inhibition. These are located in two distinct regions of Kir6.2: the N-terminus
      preceding, and the C-terminus immediately following, the transmembrane domains.
      Some mutations in the C-terminus also markedly increased the channel open
      probability, which may account for the decrease in apparent ATP sensitivity.
      Other mutations did not affect the single-channel kinetics, and may reduce ATP
      inhibition by interfering with ATP binding and/or the link between ATP binding
      and pore closure. Our results also implicate the proximal C-terminus in KATP
      channel gating.

PMID- 9628868
TI  - Embryonic lethality and abnormal cardiac myocytes in mice lacking ryanodine
      receptor type 2.
AB  - The ryanodine receptor type 2 (RyR-2) functions as a Ca2+-induced Ca2+ release
      (CICR) channel on intracellular Ca2+ stores and is distributed in most excitable
      cells with the exception of skeletal muscle cells. RyR-2 is abundantly expressed
      in cardiac muscle cells and is thought to mediate Ca2+ release triggered by Ca2+
      influx through the voltage-gated Ca2+ channel to constitute the cardiac type of
      excitation-contraction (E-C) coupling. Here we report on mutant mice lacking RyR
      2. The mutant mice died at approximately embryonic day (E) 10 with morphological
      abnormalities in the heart tube. Prior to embryonic death, large vacuolate
      sarcoplasmic reticulum (SR) and structurally abnormal mitochondria began to
      develop in the mutant cardiac myocytes, and the vacuolate SR appeared to contain
      high concentrations of Ca2+. Fluorometric Ca2+ measurements showed that a Ca2+
      transient evoked by caffeine, an activator of RyRs, was abolished in the mutant
      cardiac myocytes. However, both mutant and control hearts showed spontaneous
      rhythmic contractions at E9.5. Moreover, treatment with ryanodine, which locks
      RyR channels in their open state, did not exert a major effect on spontaneous
      Ca2+ transients in control cardiac myocytes at E9.5-11.5. These results suggest
      no essential contribution of the RyR-2 to E-C coupling in cardiac myocytes during
      early embryonic stages. Our results from the mutant mice indicate that the major
      role of RyR-2 is not in E-C coupling as the CICR channel in embryonic cardiac
      myocytes but it is absolutely required for cellular Ca2+ homeostasis most
      probably as a major Ca2+ leak channel to maintain the developing SR.

PMID- 9628867
TI  - A neuronal two P domain K+ channel stimulated by arachidonic acid and
      polyunsaturated fatty acids.
AB  - TWIK-1, TREK-1 and TASK K+ channels comprise a class of pore-forming subunits
      with four membrane-spanning segments and two P domains. Here we report the
      cloning of TRAAK, a 398 amino acid protein which is a new member of this
      mammalian class of K+ channels. Unlike TWIK-1, TREK-1 and TASK which are widely
      distributed in many different mouse tissues, TRAAK is present exclusively in
      brain, spinal cord and retina. Expression of TRAAK in Xenopus oocytes and COS
      cells induces instantaneous and non-inactivating currents that are not gated by
      voltage. These currents are only partially inhibited by Ba2+ at high
      concentrations and are insensitive to the other classical K+ channel blockers
      tetraethylammonium, 4-aminopyridine and Cs+. A particularly salient feature of
      TRAAK is that they can be stimulated by arachidonic acid (AA) and other
      unsaturated fatty acids but not by saturated fatty acids. These channels probably
      correspond to the functional class of fatty acid-stimulated K+ currents that
      recently were identified in native neuronal cells but have not yet been cloned.
      These TRAAK channels might be essential in normal physiological processes in
      which AA is known to play an important role, such as synaptic transmission, and
      also in pathophysiological processes such as brain ischemia. TRAAK channels are
      stimulated by the neuroprotective drug riluzole.

PMID- 9628869
TI  - Antagonism in the human mineralocorticoid receptor.
AB  - Key residues of the human mineralocorticoid receptor (hMR) involved in the
      recognition of agonist and antagonist ligands were identified by alanine-scanning
      mutagenesis based on a homology model of the hMR ligand-binding domain. They were
      tested for their transactivation capacity and ability to bind agonists
      (aldosterone, cortisol) and antagonists (progesterone, RU26752). The three
      dimensional model reveals two polar sites located at the extremities of the
      elongated hydrophobic ligand-binding pocket. Mutations of Gln776 and Arg817 in
      site I reduce the affinity of hMR for both agonists and antagonists and affect
      the capacity of hMR to activate transcription, suggesting that the C3-ketone
      group, common to all ligands, is anchored by these two residues conserved within
      the nuclear steroid receptor family. In contrast, mutations of Asn770 and Thr945
      in the opposite site only affect the binding of agonists bearing the C21-hydroxyl
      group. The binding of hMR antagonists that exhibit a smaller size and faster off
      rate kinetics compared with agonists is not affected. In the light of the hMR
      homology model, a new mechanism of antagonism is proposed in which the AF2-AD
      core region is destabilized by the loss of contacts between the antagonist and
      the helix H12 region.

PMID- 9628870
TI  - Involvement of distinct G-proteins, Gpa2 and Ras, in glucose- and intracellular
      acidification-induced cAMP signalling in the yeast Saccharomyces cerevisiae.
AB  - Adenylate cyclase activity in Saccharomyces cerevisiae is dependent on Ras
      proteins. Both addition of glucose to glucose-deprived (derepressed) cells and
      intracellular acidification trigger an increase in the cAMP level in vivo. We
      show that intracellular acidification, but not glucose, causes an increase in the
      GTP/GDP ratio on the Ras proteins independent of Cdc25 and Sdc25. Deletion of the
      GTPase-activating proteins Ira1 and Ira2, or expression of the RAS2(val19)
      allele, causes an enhanced GTP/GDP basal ratio and abolishes the intracellular
      acidification-induced increase. In the ira1Delta ira2Delta strain, intracellular
      acidification still triggers a cAMP increase. Glucose also did not cause an
      increase in the GTP/GDP ratio in a strain with reduced feedback inhibition of
      cAMP synthesis. Further investigation indicated that feedback inhibition by cAPK
      on cAMP synthesis acts independently of changes in the GTP/GDP ratio on Ras.
      Stimulation by glucose was dependent on the Galpha-protein Gpa2, whose deletion
      confers the typical phenotype associated with a reduced cAMP level: higher heat
      resistance, a higher level of trehalose and glycogen and elevated expression of
      STRE-controlled genes. However, the typical fluctuation in these characteristics
      during diauxic growth on glucose was still present. Overexpression of Ras2(val19)
      inhibited both the acidification- and glucose-induced cAMP increase even in a
      protein kinase A-attenuated strain. Our results suggest that intracellular
      acidification stimulates cAMP synthesis in vivo at least through activation of
      the Ras proteins, while glucose acts through the Gpa2 protein. Interaction of
      Ras2(val19) with adenylate cyclase apparently prevents its activation by both
      agonists.

PMID- 9628871
TI  - How p53 binds DNA as a tetramer.
AB  - The p53 tumor suppressor protein is a tetramer that binds sequence-specifically
      to a DNA consensus sequence consisting of two consecutive half-sites, with each
      half-site being formed by two head-to-head quarter-sites (--><-- --><--). Each
      p53 subunit binds to one quarter-site, resulting in all four DNA quarter-sites
      being occupied by one p53 tetramer. The tetramerization domain forms a symmetric
      dimer of dimers, and two contrasting models have the two DNA-binding domains of
      each dimer bound to either consecutive or alternating quarter-sites. We show here
      that the two monomers within a dimer bind to a half-site (two consecutive quarter
      sites), but not to separated (alternating) quarter-sites. Tetramers bind
      similarly, with the two dimers within each tetramer binding to pairs of half
      sites. Although one dimer within the tetramer is sufficient for binding to one
      half-site in DNA, concurrent interaction of the second dimer with a second half
      site in DNA drastically enhances binding affinity (at least 50-fold). This
      cooperative dimer-dimer interaction occurs independently of tetramerization and
      is a primary mechanism responsible for the stabilization of p53 DNA binding.
      Based on these findings, we present a model of p53 binding to the consensus
      sequence, with the tetramer binding DNA as a pair of clamps.

PMID- 9628872
TI  - The molecular basis of viral oncolysis: usurpation of the Ras signaling pathway
      by reovirus.
AB  - NIH-3T3 cells, which are resistant to reovirus infection, became susceptible when
      transformed with activated Sos or Ras. Restriction of reovirus proliferation in
      untransformed NIH-3T3 cells was not at the level of viral gene transcription, but
      rather at the level of viral protein synthesis. An analysis of cell lysates
      revealed that a 65 kDa protein was phosphorylated in untransformed NIH-3T3 cells,
      but only after infection with reovirus. This protein was not phosphorylated in
      infected or uninfected transformed cells. The 65 kDa protein was determined to be
      the double-stranded RNA-activated protein kinase (PKR), whose phosphorylation
      leads to translation inhibition. Inhibition of PKR phosphorylation by 2
      aminopurine, or deletion of the Pkr gene, led to drastic enhancement of reovirus
      protein synthesis in untransformed cells. The emerging picture is one in which
      early viral transcripts trigger PKR phosphorylation in untransformed cells, which
      in turn leads to inhibition of translation of viral genes; this phosphorylation
      event is blocked by an element(s) in the Ras pathway in the transformed cells,
      allowing viral protein synthesis to ensue. The usurpation of the Ras signaling
      pathway therefore constitutes the basis of reovirus oncolysis.

PMID- 9628873
TI  - Leptomycin B-sensitive nuclear export of MAPKAP kinase 2 is regulated by
      phosphorylation.
AB  - To study the intracellular localization of MAPKAP kinase 2 (MK2), which carries a
      putative bipartite nuclear localization signal (NLS), we constructed a green
      fluorescent protein-MAPKAP kinase 2 fusion protein (GFP-MK2). In transfected
      cells, this protein is located predominantly in the nucleus; unexpectedly, upon
      stress, it rapidly translocates to the cytoplasm. This translocation can be
      blocked by the p38 MAP kinase inhibitor SB203580, indicating its regulation by
      phosphorylation. Molecular mimicry of MK2 phosphorylation at T317 in GFP-MK2 led
      to a mutant which is located almost exclusively in the cytoplasm of the cell,
      whereas the mutant T317A shows no stress-induced redistribution. Since leptomycin
      B, which inhibits the interaction of exportin 1 with the Rev-type leucine-rich
      nuclear export signal (NES), blocks stress-dependent translocation of GFP-MK2, it
      is supposed that phosphorylation-induced export of the protein causes the
      translocation. We have identified the region responsible for nuclear export in
      MK2 which is partially overlapping with and C-terminal to the autoinhibitory
      motif. This region contains a cluster of hydrophobic amino acids in the
      characteristic spacing of a leucine-rich Rev-type NES which is necessary to
      direct GFP-MK2 to the cytoplasm. However, unlike the Rev-type NES, this region
      alone is not sufficient for nuclear export. The data obtained indicate that MK2
      contains a constitutively active NLS and a stress-regulated signal for nuclear
      export. KEYWORDS: nuclear export/nuclear import/protein phosphorylation/signal
      transduction/stress response

PMID- 9628874
TI  - PRAK, a novel protein kinase regulated by the p38 MAP kinase.
AB  - We have identified and cloned a novel serine/ threonine kinase, p38
      regulated/activated protein kinase (PRAK). PRAK is a 471 amino acid protein with
      20-30% sequence identity to the known MAP kinase-regulated protein kinases
      RSK1/2/3, MNK1/2 and MAPKAP-K2/3. PRAK was found to be expressed in all human
      tissues and cell lines examined. In HeLa cells, PRAK was activated in response to
      cellular stress and proinflammatory cytokines. PRAK activity was regulated by
      p38alpha and p38beta both in vitro and in vivo and Thr182 was shown to be the
      regulatory phosphorylation site. Activated PRAK in turn phosphorylated small heat
      shock protein 27 (HSP27) at the physiologically relevant sites. An in-gel kinase
      assay demonstrated that PRAK is a major stress-activated kinase that can
      phosphorylate small heat shock protein, suggesting a potential role for PRAK in
      mediating stress-induced HSP27 phosphorylation in vivo.

PMID- 9628875
TI  - Differential endocytic routing of homo- and hetero-dimeric ErbB tyrosine kinases
      confers signaling superiority to receptor heterodimers.
AB  - Both homo- and hetero-dimers of ErbB receptor tyrosine kinases mediate signaling
      by a large group of epidermal growth factor (EGF)-like ligands. However, some
      ligands are more potent than others, although they bind to the same direct
      receptor. In addition, signaling by receptor heterodimers is superior to
      homodimers. We addressed the mechanism underlying these two features of signal
      tuning by using three ligands: EGF; transforming growth factor alpha (TGFalpha);
      and their chimera, denoted E4T, which act on cells singly expressing ErbB-1 as a
      weak, a strong, and a very strong agonist, respectively. Co-expression of ErbB-2,
      a developmentally important co-receptor whose expression is frequently elevated
      in human cancers, specifically potentiated EGF signaling to the level achieved by
      TGFalpha, an effect that was partially mimicked by ErbB-3. Analysis of the
      mechanism underlying this trans-potentiation implied that EGF-driven homodimers
      of ErbB-1 are destined for intracellular degradation, whereas the corresponding
      heterodimers with ErbB-2 or with ErbB-3, dissociate in the early endosome. As a
      consequence, in the presence of either co-receptor, ErbB-1 is recycled to the
      cell surface and its signaling is enhanced. This latter route is followed by
      TGFalpha-driven homodimers of ErbB-1, and also by E4T-bound receptors, whose
      signaling is further enhanced by repeated cycles of binding and dissociation from
      the receptors. We conclude that alternative endocytic routes of homo- and hetero
      dimeric receptor complexes may contribute to tuning and diversification of signal
      transduction. In addition, the ability of ErbB-2 to shunt ligand-activated
      receptors to recycling may explain, in part, its oncogenic potential.

PMID- 9628877
TI  - Regulation of Hox gene expression and posterior development by the Xenopus caudal
      homologue Xcad3.
AB  - The caudal gene codes for a homeodomain transcription factor that is required for
      normal posterior development in Drosophila. In this study the biological
      activities of the Xenopus caudal (Cdx) family member Xcad3 are examined. A series
      of domain-swapping experiments demonstrate that the N-terminus of Xcad3 is
      necessary for it to activate Hox gene expression and that this function can be
      replaced by the activation domain from the viral protein VP16. In addition,
      experiments using an Xcad3 repressor mutant (XcadEn-R), which potently blocks the
      activity of wild-type Xcad3, are reported. Overexpression of XcadEn-R in embryos
      inhibits the activation of the same subset of Hox genes that are activated by
      wild-type Xcad3 and leads to a dramatic disruption of posterior development. We
      show that Xcad3 is an immediate early target of the FGF signalling pathway and
      that Xcad3 posteriorizes anterior neural tissue in a similar way to FGF.
      Furthermore, Xcad3 is required for the activation of Hox genes by FGFs. These
      data provide strong evidence that Xcad3 is required for normal posterior
      development and that it regulates the expression of the Hox genes downstream of
      FGF signalling.

PMID- 9628876
TI  - Two distinct nuclear receptor interaction domains in NSD1, a novel SET protein
      that exhibits characteristics of both corepressors and coactivators.
AB  - NSD1, a novel 2588 amino acid mouse nuclear protein that interacts directly with
      the ligand-binding domain (LBD) of several nuclear receptors (NRs), has been
      identified and characterized. NSD1 contains a SET domain and multiple PHD
      fingers. In addition to these conserved domains found in both positive and
      negative Drosophila chromosomal regulators, NSD1 contains two distinct NR
      interaction domains, NID-L and NID+L, that exhibit binding properties of NIDs
      found in NR corepressors and coactivators, respectively. NID-L, but not NID+L,
      interacts with the unliganded LBDs of retinoic acid receptors (RAR) and thyroid
      hormone receptors (TR), and this interaction is severely impaired by mutations in
      the LBD alpha-helix 1 that prevent binding of corepressors and transcriptional
      silencing by apo-NRs. NID+L, but not NID-L, interacts with the liganded LBDs of
      RAR, TR, retinoid X receptor (RXR), and estrogen receptor (ER), and this
      interaction is abrogated by mutations in the LBD alpha-helix 12 that prevent
      binding of coactivators of the ligand-induced transcriptional activation function
      AF-2. A novel variant (FxxLL) of the NR box motif (LxxLL) is present in NID+L and
      is required for the binding of NSD1 to holo-LBDs. Interestingly, NSD1 contains
      separate repression and activation domains. Thus, NSD1 may define a novel class
      of bifunctional transcriptional intermediary factors playing distinct roles in
      both the presence and absence of ligand.

PMID- 9628878
TI  - In vitro chromatin remodelling by chromatin accessibility complex (CHRAC) at the
      SV40 origin of DNA replication.
AB  - DNA replication is initiated by binding of initiation factors to the origin of
      replication. Nucleosomes are known to inhibit the access of the replication
      machinery to origin sequences. Recently, nucleosome remodelling factors have been
      identified that increase the accessibility of nucleosomal DNA to transcription
      regulators. To test whether the initiation of DNA replication from an origin
      covered by nucleosomes would also benefit from the action of nucleosome
      remodelling factors, we reconstituted SV40 DNA into chromatin in Drosophila
      embryo extracts. In the presence of T-antigen and ATP, a chromatin-associated
      cofactor allowed efficient replication from a nucleosomal origin in vitro. In
      search of the energy-dependent cofactor responsible we found that purified
      'chromatin accessibility complex' (CHRAC) was able to alter the nucleosomal
      structure at the origin allowing the binding of T-antigen and efficient
      initiation of replication. These experiments provide evidence for the involvement
      of a nucleosome remodelling machine in structural changes at the SV40 origin of
      DNA replication in vitro.

PMID- 9628879
TI  - Transcription activation at Class II CRP-dependent promoters: identification of
      determinants in the C-terminal domain of the RNA polymerase alpha subunit.
AB  - Many transcription factors, including the Escherichia coli cyclic AMP receptor
      protein (CRP), act by making direct contacts with RNA polymerase. At Class II CRP
      dependent promoters, CRP activates transcription by making two such contacts: (i)
      an interaction with the RNA polymerase alpha subunit C-terminal domain (alphaCTD)
      that facilitates initial binding of RNA polymerase to promoter DNA; and (ii) an
      interaction with the RNA polymerase alpha subunit N-terminal domain that
      facilitates subsequent promoter opening. We have used random mutagenesis and
      alanine scanning to identify determinants within alphaCTD for transcription
      activation at a Class II CRP-dependent promoter. Our results indicate that Class
      II CRP-dependent transcription requires the side chains of residues 265, 271, 285
      288 and 317. Residues 285-288 and 317 comprise a discrete 20x10 A surface on
      alphaCTD, and substitutions within this determinant reduce or eliminate
      cooperative interactions between alpha subunits and CRP, but do not affect DNA
      binding by alpha subunits. We propose that, in the ternary complex of RNA
      polymerase, CRP and a Class II CRP-dependent promoter, this determinant in
      alphaCTD interacts directly with CRP, and is distinct from and on the opposite
      face to the proposed determinant for alphaCTD-CRP interaction in Class I CRP
      dependent transcription.

PMID- 9628881
TI  - RNA stabilization by the AU-rich element binding protein, HuR, an ELAV protein.
AB  - An important paradigm for post-transcriptional regulation is the control of
      cytoplasmic mRNA stability mediated by AU-rich elements (AREs) in the 3'
      untranslated region of transcripts encoding oncoproteins, cytokines and
      transcription factors. While many RNA-binding proteins have been shown to bind to
      AREs in vitro, neither the functional consequences nor the physiological
      significance of their interactions are known. Here we demonstrate a role for the
      embryonic lethal abnormal visual (ELAV) RNA-binding protein HuR in mRNA turnover
      in vivo. The ELAV family of RNA-binding proteins is highly conserved in
      vertebrates. In humans, there are four members; HuR is expressed in all
      proliferating cells, whereas Hel-N1, HuC and HuD are expressed in terminally
      differentiated neurons. We show that elevation of cytoplasmic HuR levels inhibits
      c-fos ARE-mediated RNA decay but has little effect on rapid decay directed by c
      jun ARE. It appears that HuR has little effect on deadenylation but delays onset
      of decay of the RNA body and slows down its subsequent decay. We also show that
      HuR can be induced to redistribute from the nucleus to the cytoplasm and that
      this redistribution is associated with an altered function. Modulation of the ARE
      mediated decay pathway through controlling distribution of the ELAV proteins
      between nucleus and cytoplasm may be a mechanism by which cell growth and
      differentiation is regulated.

PMID- 9628880
TI  - Overexpression of HuR, a nuclear-cytoplasmic shuttling protein, increases the in
      vivo stability of ARE-containing mRNAs.
AB  - The messenger RNAs of many proto-oncogenes, cytokines and lymphokines are
      targeted for rapid degradation through AU-rich elements (AREs) located in their
      3' untranslated regions (UTRs). HuR, a ubiquitously expressed member of the Elav
      family of RNA binding proteins, exhibits specific affinities for ARE-containing
      RNA sequences in vitro which correlate with their in vivo decay rates, thereby
      implicating HuR in the ARE-mediated degradation pathway. We have transiently
      transfected HuR into mouse L929 cells and observed that overexpression of HuR
      enhances the stability of beta-globin reporter mRNAs containing either class I or
      class II AREs. The increase in mRNA stability parallels the level of HuR
      overexpression, establishing an in vivo role for HuR in mRNA decay. Furthermore,
      overexpression of HuR deletion mutants lacking RNA recognition motif 3 (RRM 3)
      does not exert a stabilizing effect, indicating that RRM 3 is important for HuR
      function. We have also developed polyclonal anti-HuR antibodies.
      Immunofluorescent staining of HeLa and L929 cells using affinity-purified anti
      HuR antibody shows that both endogenous and overexpressed HuR proteins are
      localized in the nucleus. By forming HeLa-L929 cell heterokaryons, we demonstrate
      that HuR shuttles between the nucleus and cytoplasm. Thus, HuR may initially bind
      to ARE-containing mRNAs in the nucleus and provide protection during and after
      their export to the cytoplasmic compartment.

PMID- 9628882
TI  - The chaperonin of the archaeon Sulfolobus solfataricus is an RNA-binding protein
      that participates in ribosomal RNA processing.
AB  - The 60 kDa molecular chaperones (chaperonins) are high molecular weight protein
      complexes having a characteristic double-ring toroidal shape; they are thought to
      aid the folding of denatured or newly synthesized polypeptides. These proteins
      exist as two functionally similar, but distantly related families, one comprising
      the bacterial and organellar chaperonins and another (the so-called CCT-TRiC
      family) including the chaperonins of the archaea and the eukaryotes. Although
      some evidence exists that the archaeal chaperonins are implicated in protein
      folding, much remains to be learned about their precise cellular function. In
      this work, we report that the chaperonin of the thermophilic archaeon Sulfolobus
      solfataricus is an RNA-binding protein that interacts specifically in vivo with
      the 16S rRNA and participates in the maturation of its 5' extremity in vitro. We
      further show that the chaperonin binds RNA as the native heterooligomeric complex
      and that RNA binding and processing are inhibited by ATP. These results agree
      with previous reports indicating a role for the bacterial/organellar chaperonins
      in RNA protection or processing and suggest that all known chaperonin families
      share specific and evolutionarily ancient functions in RNA metabolism.

PMID- 9628883
TI  - EF-G-catalyzed translocation of anticodon stem-loop analogs of transfer RNA in
      the ribosome.
AB  - Translocation, catalyzed by elongation factor EF-G, is the precise movement of
      the tRNA-mRNA complex within the ribosome following peptide bond formation. Here
      we examine the structural requirement for A- and P-site tRNAs in EF-G-catalyzed
      translocation by substituting anticodon stem-loop (ASL) analogs for the
      respective tRNAs. Translocation of mRNA and tRNA was monitored independently;
      mRNA movement was assayed by toeprinting, while tRNA and ASL movement was
      monitored by hydroxyl radical probing by Fe(II) tethered to the ASLs and by
      chemical footprinting. Translocation depends on occupancy of both A and P sites
      by tRNA bound in a mRNA-dependent fashion. The requirement for an A-site tRNA can
      be satisfied by a 15 nucleotide ASL analog comprising only a 4 base pair (bp)
      stem and a 7 nucleotide anticodon loop. Translocation of the ASL is both EF-G-
      and GTP-dependent, and is inhibited by the translocational inhibitor
      thiostrepton. These findings show that the D, T and acceptor stem regions of A
      site tRNA are not essential for EF-G-dependent translocation. In contrast, no
      translocation occurs if the P-site tRNA is substituted with an ASL, indicating
      that other elements of P-site tRNA structure are required for translocation. We
      also tested the effect of increasing the A-site ASL stem length from 4 to 33 bp
      on translocation from A to P site. Translocation efficiency decreases as the ASL
      stem extends beyond 22 bp, corresponding approximately to the maximum dimension
      of tRNA along the anticodon-D arm axis. This result suggests that a structural
      feature of the ribosome between the A and P sites, interferes with movement of
      tRNA analogs that exceed the normal dimensions of the coaxial tRNA anticodon-D
      arm.

PMID- 9628885
TI  - Influences of array size and homogeneity on minisatellite mutation.
AB  - Unstable minisatellites display high frequencies of spontaneous gain and loss of
      repeats in the human germline. Most length changes arise through complex
      recombination events including intra-allelic duplications/deletions and inter
      allelic transfers of repeats. Definition of the factors modulating instability
      requires both measurement of mutation rate and detailed analysis of mutant
      structures at the level of individual alleles. We have measured mutation rates in
      sperm for a wide range of alleles of the highly unstable human minisatellite
      CEB1. Instability varies by three orders of magnitude between alleles and
      increases steadily with the size of the tandem array. Structural analysis of
      mutant molecules derived from six alleles revealed that it is the rate of intra
      allelic rearrangements which increases with array size and that intra-allelic
      duplication events tend to cluster within homogeneous segments of alleles; both
      phenomena resemble features of trinucleotide repeat instability. In contrast,
      inter-allelic transfers occur at a fairly constant rate, irrespective of array
      length, and show a mild polarity towards one end of the minisatellite, suggesting
      the possible influence of flanking DNA on these conversion-like events.

PMID- 9628884
TI  - Binary specification of nonsense codons by splicing and cytoplasmic translation.
AB  - Premature translation termination codons resulting from nonsense or frameshift
      mutations are common causes of genetic disorders. Complications arising from the
      synthesis of C-terminally truncated polypeptides can be avoided by 'nonsense
      mediated decay' of the mutant mRNAs. Premature termination codons in the beta
      globin mRNA cause the common recessive form of beta-thalassemia when the affected
      mRNA is degraded, but the more severe dominant form when the mRNA escapes
      nonsense-mediated decay. We demonstrate that cells distinguish a premature
      termination codon within the beta-globin mRNA from the physiological translation
      termination codon by a two-step specification mechanism. According to the binary
      specification model proposed here, the positions of splice junctions are first
      tagged during splicing in the nucleus, defining a stop codon operationally as a
      premature termination codon by the presence of a 3' splicing tag. In the second
      step, cytoplasmic translation is required to validate the 3' splicing tag for
      decay of the mRNA. This model explains nonsense-mediated decay on the basis of
      conventional molecular mechanisms and allows us to propose a common principle for
      nonsense-mediated decay from yeast to man.

PMID- 9628886
TI  - Different cis-regulatory DNA elements mediate developmental stage- and tissue
      specific expression of the human COL2A1 gene in transgenic mice.
AB  - Expression of the type II collagen gene (human COL2A1, mouse Col2a1) heralds the
      differentiation of chondrocytes. It is also expressed in progenitor cells of some
      nonchondrogenic tissues during embryogenesis. DNA sequences in the 5' flanking
      region and intron 1 are known to control tissue-specific expression in vitro, but
      the regulation of COL2A1 expression in vivo is not clearly understood. We have
      tested the regulatory activity of DNA sequences from COL2A1 on the expression of
      a lacZ reporter gene in transgenic mice. We have found that type II collagen
      characteristic expression of the transgene requires the enhancer activity of a
      309-bp fragment (+2, 388 to +2,696) in intron 1 in conjunction with 6.1-kb 5'
      sequences. Different regulatory elements were found in the 1.6-kb region (+701 to
      +2,387) of intron 1 which only needs 90-bp 5' sequences for tissue-specific
      expression in different components of the developing cartilaginous skeleton.
      Distinct positive and negative regulatory elements act together to control tissue
      specific transgene expression in the developing midbrain neuroepithelium.
      Positive elements affecting expression in the midbrain were found in the region
      from -90 to -1,500 and from +701 to +2,387, whereas negatively acting elements
      were detected in the regions from -1,500 to -6,100 and +2,388 to +2,855.

PMID- 9628887
TI  - Interaction of vault particles with estrogen receptor in the MCF-7 breast cancer
      cell.
AB  - A 104-kD protein was coimmunoprecipitated with the estrogen receptor from the
      flowtrough of a phosphocellulose chromatography of MCF-7 cell nuclear extract.
      mAbs to this protein identified several cDNA clones coding for the human 104-kD
      major vault protein. Vaults are large ribonucleoprotein particles of unknown
      function present in all eukaryotic cells. They have a complex morphology,
      including several small molecules of RNA, but a single protein species, the major
      vault protein, accounts for >70% of their mass. Their shape is reminiscent of the
      nucleopore central plug, but no proteins of known function have been described to
      interact with them. Western blot analysis of vaults purified on sucrose gradient
      showed the presence of estrogen receptor co-migrating with the vault peak. The
      AER317 antibody to estrogen receptor coimmunoprecipitated the major vault protein
      and the vault RNA also in the 20,000 g supernatant fraction. Reconstitution
      experiments of estrogen receptor fragments with the major vault protein mapped
      the site of the interaction between amino acids 241 and 280 of human estrogen
      receptor, where the nuclear localization signal sequences are located. Estradiol
      treatment of cells increased the amount of major vault protein present in the
      nuclear extract and coimmunoprecipitated with estrogen receptor, whereas the anti
      estrogen ICI182,780 had no effect. The hormone-dependent interaction of vaults
      with estrogen receptor was reproducible in vitro and was prevented by sodium
      molybdate. Antibodies to progesterone and glucocorticoid receptors were able to
      coimmunoprecipitate the major vault protein. The association of nuclear receptors
      with vaults could be related to their intracellular traffic.

PMID- 9628888
TI  - GalNAc-alpha-O-benzyl inhibits NeuAcalpha2-3 glycosylation and blocks the
      intracellular transport of apical glycoproteins and mucus in differentiated HT-29
      cells.
AB  - Exposure for 24 h of mucus-secreting HT-29 cells to the sugar analogue GalNAc
      alpha-O-benzyl results in inhibition of Galbeta1-3GalNAc:alpha2,3
      sialyltransferase, reduced mucin sialylation, and inhibition of their secretion
      (Huet, G., I. Kim, C. de Bolos, J.M. Loguidice, O. Moreau, B. Hemon, C. Richet,
      P. Delannoy, F.X. Real., and P. Degand. 1995. J. Cell Sci. 108:1275-1285). To
      determine the effects of prolonged inhibition of sialylation, differentiated HT
      29 populations were grown under permanent exposure to GalNAc-alpha-O-benzyl. This
      results in not only inhibition of mucus secretion, but also in a dramatic
      swelling of the cells and the accumulation in intracytoplasmic vesicles of brush
      border-associated glycoproteins like dipeptidylpeptidase-IV, the mucin-like
      glycoprotein MUC1, and carcinoembryonic antigen which are no longer expressed at
      the apical membrane. The block occurs beyond the cis-Golgi as substantiated by
      endoglycosidase treatment and biosynthesis analysis. In contrast, the polarized
      expression of the basolateral glycoprotein GP 120 is not modified. Underlying
      these effects we found that (a) like in mucins, NeuAcalpha2-3Gal-R is expressed
      in the terminal position of the oligosaccharide species associated with the
      apical, but not the basolateral glycoproteins of the cells, and (b) treatment
      with GalNAc-alpha-O-benzyl results in an impairment of their sialylation. These
      effects are reversible upon removal of the drug. It is suggested that alpha2-3
      sialylation is involved in apical targeting of brush border membrane
      glycoproteins and mucus secretion in HT-29 cells.

PMID- 9628889
TI  - The protozoan parasite Toxoplasma gondii targets proteins to dense granules and
      the vacuolar space using both conserved and unusual mechanisms.
AB  - All known proteins that accumulate in the vacuolar space surrounding the obligate
      intracellular protozoan parasite Toxoplasma gondii are derived from parasite
      dense granules. To determine if constitutive secretory vesicles could also
      mediate delivery to the vacuolar space, T. gondii was stably transfected with
      soluble Escherichia coli alkaline phosphatase and E. coli beta-lactamase.
      Surprisingly, both foreign secretory reporters were delivered quantitatively into
      parasite dense granules and efficiently secreted into the vacuolar space.
      Addition of a glycosylphosphatidylinositol membrane anchor rerouted alkaline
      phosphatase to the parasite surface. Alkaline phosphatase fused to the
      transmembrane domain and cytoplasmic tail from the endogenous dense granule
      protein GRA4 localized to dense granules. The protein was secreted into a
      tuboreticular network in the vacuolar space, in a fashion dependent upon the
      cytoplasmic tail, but not upon a tyrosine-based motif within the tail. Alkaline
      phosphatase fused to the vesicular stomatitis virus G protein transmembrane
      domain and cytoplasmic tail localized primarily to the Golgi, although staining
      of dense granules and the intravacuolar network was also detected; truncating the
      cytoplasmic tail decreased Golgi staining and increased delivery to dense
      granules but blocked delivery to the intravacuolar network. Targeting of secreted
      proteins to T. gondii dense granules and the plasma membrane uses general
      mechanisms identified in higher eukaryotic cells but is simplified and
      exaggerated in scope, while targeting of secreted proteins beyond the boundaries
      of the parasite involves unusual sorting events.

PMID- 9628890
TI  - Specific single or double proline substitutions in the "spring-loaded" coiled
      coil region of the influenza hemagglutinin impair or abolish membrane fusion
      activity.
AB  - We tested the role of the "spring-loaded" conformational change in the fusion
      mechanism of the influenza hemagglutinin (HA) by assessing the effects of 10
      point mutants in the region of high coiled-coil propensity, HA2 54-81. The
      mutants included proline substitutions at HA2 55, 71, and 80, as well as a double
      proline substitution at residues 55 and 71. Mutants were expressed in COS or 293T
      cells and assayed for cell surface expression and structural features as well as
      for their ability to change conformation and induce fusion at low pH. We found
      the following: Specific mutations affected the precise carbohydrate structure and
      folding of the HA trimer. All of the mutants, however, formed trimers that could
      be expressed at the cell surface in a form that could be proteolytically cleaved
      from the precursor, HA0, to the fusion-permissive form, HA1-S-S-HA2. All mutants
      reacted with an antibody against the major antigenic site and bound red blood
      cells. Seven out of ten mutants displayed a wild-type (wt) or moderately elevated
      pH dependence for the conformational change. V55P displayed a substantial
      reduction (approximately 60- 80%) in the initial rate of lipid mixing. The other
      single mutants displayed efficient fusion with the same pH dependence as wt-HA.
      The double proline mutant V55P/ S71P displayed no fusion activity despite being
      well expressed at the cell surface as a proteolytically cleaved trimer that could
      bind red blood cells and change conformation at low pH. The impairment in fusion
      for both V55P and V55P/S71P was at the level of outer leaflet lipid mixing. We
      interpret our results in support of the hypothesis that the spring-loaded
      conformational change is required for fusion. An alternate model is discussed.

PMID- 9628891
TI  - A calcium signaling cascade essential for myosin thick filament assembly in
      Xenopus myocytes.
AB  - Spontaneous calcium release from intracellular stores occurs during
      myofibrillogenesis, the process of sarcomeric protein assembly in striated
      muscle. Preventing these Ca2+ transients disrupts sarcomere formation, but the
      signal transduction cascade has not been identified. Here we report that specific
      blockade of Ca2+ release from the ryanodine receptor (RyR) activated Ca2+ store
      blocks transients and disrupts myosin thick filament (A band) assembly.
      Inhibition of an embryonic Ca2+/calmodulin-dependent myosin light chain kinase
      (MLCK) by blocking the ATP-binding site, by allosteric phosphorylation, or by
      intracellular delivery of a pseudosubstrate peptide, also disrupts sarcomeric
      organization. The results indicate that both RyRs and MLCK, which have well
      described calcium signaling roles in mature muscle contraction, have essential
      developmental roles during construction of the contractile apparatus.

PMID- 9628892
TI  - The Src homology domain 3 (SH3) of a yeast type I myosin, Myo5p, binds to
      verprolin and is required for targeting to sites of actin polarization.
AB  - The budding yeast contains two type I myosins, Myo3p and Myo5p, with redundant
      functions. Deletion of both myosins results in growth defects, loss of actin
      polarity and polarized cell surface growth, and accumulation of intracellular
      membranes. Expression of myc-tagged Myo5p in myo3Delta myo5Delta cells fully
      restores wild-type characteristics. Myo5p is localized as punctate, cortical
      structures enriched at sites of polarized cell growth. We find that latrunculin-A
      induced depolymerization of F-actin results in loss of Myo5p patches. Moreover,
      incubation of yeast cells at 37 degrees C results in transient depolarization of
      both Myo5p patches and the actin cytoskeleton. Mutant Myo5 proteins with
      deletions in nonmotor domains were expressed in myo3Delta myo5Delta cells and the
      resulting strains were analyzed for Myo5p function. Deletion of the tail homology
      2 (TH2) domain, previously implicated in ATP-insensitive actin binding, has no
      detectable effect on Myo5p function. In contrast, myo3Delta myo5Delta cells
      expressing mutant Myo5 proteins with deletions of the src homology domain 3 (SH3)
      or both TH2 and SH3 domains display defects including Myo5p patch depolarization,
      actin disorganization, and phenotypes associated with actin dysfunction. These
      findings support a role for the SH3 domain in Myo5p localization and function in
      budding yeast. The proline-rich protein verprolin (Vrp1p) binds to the SH3 domain
      of Myo3p or Myo5p in two-hybrid tests, coimmunoprecipitates with Myo5p, and
      colocalizes with Myo5p. Immunolocalization of the myc-tagged SH3 domain of Myo5p
      reveals diffuse cytoplasmic staining. Thus, the SH3 domain of Myo5p contributes
      to but is not sufficient for localization of Myo5p either to patches or to sites
      of polarized cell growth. Consistent with this, Myo5p patches assemble but do not
      localize to sites of polarized cell surface growth in a VRP1 deletion mutant. Our
      studies support a multistep model for Myo5p targeting in yeast. The first step,
      assembly of Myo5p patches, is dependent upon F-actin, and the second step,
      polarization of actin patches, requiresVrp1p and the SH3 domain of Myo5p.

PMID- 9628893
TI  - Interaction between mitochondria and the actin cytoskeleton in budding yeast
      requires two integral mitochondrial outer membrane proteins, Mmm1p and Mdm10p.
AB  - Transfer of mitochondria to daughter cells during yeast cell division is
      essential for viable progeny. The actin cytoskeleton is required for this
      process, potentially as a track to direct mitochondrial movement into the bud.
      Sedimentation assays reveal two different components required for mitochondria
      actin interactions: (1) mitochondrial actin binding protein(s) (mABP), a
      peripheral mitochondrial outer membrane protein(s) with ATP-sensitive actin
      binding activity, and (2) a salt-inextractable, presumably integral, membrane
      protein(s) required for docking of mABP on the organelle. mABP activity is
      abolished by treatment of mitochondria with high salt. Addition of either the
      salt-extracted mitochondrial peripheral membrane proteins (SE), or a protein
      fraction with ATP-sensitive actin-binding activity isolated from SE, to salt
      washed mitochondria restores this activity. mABP docking activity is saturable,
      resistant to high salt, and inhibited by pre-treatment of salt-washed
      mitochondria with papain. Two integral mitochondrial outer membrane proteins,
      Mmm1p (Burgess, S.M., M. Delannoy, and R.E. Jensen. 1994. J.Cell Biol. 126:1375
      1391) and Mdm10p, (Sogo, L.F., and M.P. Yaffe. 1994. J.Cell Biol. 126:1361- 1373)
      are required for these actin-mitochondria interactions. Mitochondria isolated
      from an mmm1-1 temperature-sensitive mutant or from an mdm10 deletion mutant show
      no mABP activity and no mABP docking activity. Consistent with this,
      mitochondrial motility in vivo in mmm1-1 and mdm10Delta mutants appears to be
      actin independent. Depolymerization of F-actin using latrunculin-A results in
      loss of long-distance, linear movement and a fivefold decrease in the velocity of
      mitochondrial movement. Mitochondrial motility in mmm1-1 and mdm10Delta mutants
      is indistinguishable from that in latrunculin-A-treated wild-type cells. We
      propose that Mmm1p and Mdm10p are required for docking of mABP on the surface of
      yeast mitochondria and coupling the organelle to the actin cytoskeleton.

PMID- 9628894
TI  - Spindle assembly and mitosis without centrosomes in parthenogenetic Sciara
      embryos.
AB  - In Sciara, unfertilized embryos initiate parthenogenetic development without
      centrosomes. By comparing these embryos with normal fertilized embryos, spindle
      assembly and other microtubule-based events can be examined in the presence and
      absence of centrosomes. In both cases, functional mitotic spindles are formed
      that successfully proceed through anaphase and telophase, forming two daughter
      nuclei separated by a midbody. The spindles assembled without centrosomes are
      anastral, and it is likely that their microtubules are nucleated at or near the
      chromosomes. These spindles undergo anaphase B and successfully segregate sister
      chromosomes. However, without centrosomes the distance between the daughter
      nuclei in the next interphase is greatly reduced. This suggests that centrosomes
      are required to maintain nuclear spacing during the telophase to interphase
      transition. As in Drosophila, the initial embryonic divisions of Sciara are
      synchronous and syncytial. The nuclei in fertilized centrosome-bearing embryos
      maintain an even distribution as they divide and migrate to the cortex. In
      contrast, as division proceeds in embryos lacking centrosomes, nuclei collide and
      form large irregularly shaped nuclear clusters. These nuclei are not evenly
      distributed and never successfully migrate to the cortex. This phenotype is
      probably a direct result of a failure to form astral microtubules in
      parthenogenetic embryos lacking centrosomes. These results indicate that the
      primary function of centrosomes is to provide astral microtubules for proper
      nuclear spacing and migration during the syncytial divisions. Fertilized Sciara
      embryos produce a large population of centrosomes not associated with nuclei.
      These free centrosomes do not form spindles or migrate to the cortex and
      replicate at a significantly reduced rate. This suggests that the centrosome must
      maintain a proper association with the nucleus for migration and normal
      replication to occur.

PMID- 9628895
TI  - Mammalian p55CDC mediates association of the spindle checkpoint protein Mad2 with
      the cyclosome/anaphase-promoting complex, and is involved in regulating anaphase
      onset and late mitotic events.
AB  - We have investigated the function of p55CDC, a mammalian protein related to Cdc20
      and Hct1/Cdh1 in Saccharomyces cerevisiae, and Fizzy and Fizzy-related in
      Drosophila. Immunofluorescence studies and expression of a p55CDC-GFP chimera
      demonstrate that p55CDC is concentrated at the kinetochores in M phase cells from
      late prophase to telophase. Some p55CDC is also associated with the spindle
      microtubules and spindle poles, and some is diffuse in the cytoplasm. At
      anaphase, the concentration of p55CDC at the kinetochores gradually diminishes,
      and is gone by late telophase. In extracts prepared from M phase, but not from
      interphase HeLa cells, p55CDC coimmunoprecipitates with three important elements
      of the M phase checkpoint machinery: Cdc27, Cdc16, and Mad2. p55CDC is required
      for binding Mad2 with the Cdc27 and Cdc16. Thus, it is likely that p55CDC
      mediates the association of Mad2 with the cyclosome/anaphase-promoting complex.
      Microinjection of anti-p55CDC antibody into mitotic mammalian cells induces
      arrest or delay at metaphase, and impairs progression of late mitotic events.
      These studies suggest that mammalian p55CDC may be part of a regulatory and
      targeting complex for the anaphase-promoting complex.

PMID- 9628896
TI  - OCI-5/GPC3, a glypican encoded by a gene that is mutated in the Simpson-Golabi
      Behmel overgrowth syndrome, induces apoptosis in a cell line-specific manner.
AB  - OCI-5/GPC3 is a member of the glypican family. Glypicans are heparan sulfate
      proteoglycans that are bound to the cell surface through a glycosyl
      phosphatidylinositol anchor. It has recently been shown that the OCI-5/GPC3 gene
      is mutated in patients with the Simpson-Golabi-Behmel Syndrome (SGBS), an X
      linked disorder characterized by pre- and postnatal overgrowth and various
      visceral and skeletal dysmorphisms. Some of these dysmorphisms could be the
      result of deficient growth inhibition or apoptosis in certain cell types during
      development. Here we present evidence indicating that OCI-5/GPC3 induces
      apoptosis in cell lines derived from mesothelioma (II14) and breast cancer (MCF
      7). This induction, however, is cell line specific since it is not observed in
      NIH 3T3 fibroblasts or HT-29 colorectal tumor cells. We also show that the
      apoptosis-inducing activity in II14 and MCF-7 cells requires the anchoring of OCI
      5/GPC3 to the cell membrane. The glycosaminoglycan chains, on the other hand, are
      not required. MCF-7 cells can be rescued from OCI-5/GPC3-induced cell death by
      insulin-like growth factor 2. This factor has been implicated in Beckwith
      Wiedemann, an overgrowth syndrome that has many similarities with SGBS. The
      discovery that OCI-5/GPC3 is able to induce apoptosis in a cell line- specific
      manner provides an insight into the mechanism that, at least in part, is
      responsible for the phenotype of SGBS patients.

PMID- 9628897
TI  - A giant ubiquitin-conjugating enzyme related to IAP apoptosis inhibitors.
AB  - Ubiquitin-conjugating enzymes (UBC) catalyze the covalent attachment of ubiquitin
      to target proteins and are distinguished by the presence of a UBC domain required
      for catalysis. Previously identified members of this enzyme family are small
      proteins and function primarily in selective proteolysis pathways. Here we
      describe BRUCE (BIR repeat containing ubiquitin-conjugating enzyme), a giant (528
      kD) ubiquitin-conjugating enzyme from mice. BRUCE is membrane associated and
      localizes to the Golgi compartment and the vesicular system. Remarkably, in
      addition to being an active ubiquitin-conjugating enzyme, BRUCE bears a
      baculovirus inhibitor of apoptosis repeat (BIR) motif, which to this date has
      been exclusively found in apoptosis inhibitors of the IAP-related protein family.
      The BIR motifs of IAP proteins are indispensable for their anti-cell death
      activity and are thought to function through protein-protein interaction. This
      suggests that BRUCE may combine properties of IAP-like proteins and ubiquitin
      conjugating enzymes and indicates that the family of IAP-like proteins is
      structurally and functionally more diverse than previously expected.

PMID- 9628898
TI  - The regulation of reactive oxygen species production during programmed cell
      death.
AB  - Reactive oxygen species (ROS) are thought to be involved in many forms of
      programmed cell death. The role of ROS in cell death caused by oxidative
      glutamate toxicity was studied in an immortalized mouse hippocampal cell line
      (HT22). The causal relationship between ROS production and glutathione (GSH)
      levels, gene expression, caspase activity, and cytosolic Ca2+ concentration was
      examined. An initial 5-10-fold increase in ROS after glutamate addition is
      temporally correlated with GSH depletion. This early increase is followed by an
      explosive burst of ROS production to 200-400-fold above control values. The
      source of this burst is the mitochondrial electron transport chain, while only 5
      10% of the maximum ROS production is caused by GSH depletion. Macromolecular
      synthesis inhibitors as well as Ac-YVAD-cmk, an interleukin 1beta-converting
      enzyme protease inhibitor, block the late burst of ROS production and protect
      HT22 cells from glutamate toxicity when added early in the death program.
      Inhibition of intracellular Ca2+ cycling and the influx of extracellular Ca2+
      also blocks maximum ROS production and protects the cells. The conclusion is that
      GSH depletion is not sufficient to cause the maximal mitochondrial ROS
      production, and that there is an early requirement for protease activation,
      changes in gene expression, and a late requirement for Ca2+ mobilization.

PMID- 9628899
TI  - Differential nuclear translocation and transactivation potential of beta-catenin
      and plakoglobin.
AB  - beta-Catenin and plakoglobin are homologous proteins that function in cell
      adhesion by linking cadherins to the cytoskeleton and in signaling by
      transactivation together with lymphoid-enhancing binding/T cell (LEF/TCF)
      transcription factors. Here we compared the nuclear translocation and
      transactivation abilities of beta-catenin and plakoglobin in mammalian cells.
      Overexpression of each of the two proteins in MDCK cells resulted in nuclear
      translocation and formation of nuclear aggregates. The beta-catenin-containing
      nuclear structures also contained LEF-1 and vinculin, while plakoglobin was
      inefficient in recruiting these molecules, suggesting that its interaction with
      LEF-1 and vinculin is significantly weaker. Moreover, transfection of LEF-1
      translocated endogenous beta-catenin, but not plakoglobin to the nucleus.
      Chimeras consisting of Gal4 DNA-binding domain and the transactivation domains of
      either plakoglobin or beta-catenin were equally potent in transactivating a Gal4
      responsive reporter, whereas activation of LEF-1- responsive transcription was
      significantly higher with beta-catenin. Overexpression of wild-type plakoglobin
      or mutant beta-catenin lacking the transactivation domain induced accumulation of
      the endogenous beta-catenin in the nucleus and LEF-1-responsive transactivation.
      It is further shown that the constitutive beta-catenin-dependent transactivation
      in SW480 colon carcinoma cells and its nuclear localization can be inhibited by
      overexpressing N-cadherin or alpha-catenin. The results indicate that (a)
      plakoglobin and beta-catenin differ in their nuclear translocation and complexing
      with LEF-1 and vinculin; (b) LEF-1-dependent transactivation is preferentially
      driven by beta-catenin; and (c) the cytoplasmic partners of beta-catenin,
      cadherin and alpha-catenin, can sequester it to the cytoplasm and inhibit its
      transcriptional activity.

PMID- 9628901
TI  - Cadherin-6 mediates the heterotypic interactions between the hemopoietic
      osteoclast cell lineage and stromal cells in a murine model of osteoclast
      differentiation.
AB  - Osteoclasts are multinucleated cells of hemopoietic origin that are responsible
      for bone resorption during physiological bone remodeling and in a variety of bone
      diseases. Osteoclast development requires direct heterotypic cell-cell
      interactions of the hemopoietic osteoclast precursors with the neighboring
      osteoblast/stromal cells. However, the molecular mechanisms underlying these
      heterotypic interactions are poorly understood. We isolated cadherin-6 isoform,
      denoted cadherin-6/2 from a cDNA library of human osteoclast-like cells. The
      isolated cadherin-6/2 is 3,423 bp in size consisting of an open reading frame of
      2,115 bp, which encodes 705 amino acids. This isoform lacks 85 amino acids
      between positions 333 and 418 and contains 9 different amino acids in the
      extracellular domain compared with the previously described cadherin-6. The human
      osteoclast-like cells also expressed another isoform denoted cadherin-6/1
      together with the cadherin-6. Introduction of cadherin-6/2 into L-cells that
      showed no cell-cell contact caused evident morphological changes accompanied with
      tight cell-cell association, indicating the cadherin-6/2 we isolated here is
      functional. Moreover, expression of dominant-negative or antisense cadherin-6/2
      construct in bone marrow-derived mouse stromal ST2 cells, which express only
      cadherin-6/2, markedly impaired their ability to support osteoclast formation in
      a mouse coculture model of osteoclastogenesis. Our results suggest that cadherin
      6 may be a contributory molecule to the heterotypic interactions between the
      hemopoietic osteoclast cell lineage and osteoblast/bone marrow stromal cells
      required for the osteoclast differentiation. Since both osteoclasts and
      osteoblasts/bone marrow stromal cells are the primary cells controlling
      physiological bone remodeling, expression of cadherin-6 isoforms in these two
      cell types of different origin suggests a critical role of these molecules in the
      relationship of osteoclast precursors and cells of osteoblastic lineage within
      the bone microenvironment.

PMID- 9628900
TI  - Tyrosine phosphorylation and src family kinases control keratinocyte cell-cell
      adhesion.
AB  - In their progression from the basal to upper differentiated layers of the
      epidermis, keratinocytes undergo significant structural changes, including
      establishment of close intercellular contacts. An important but so far unexplored
      question is how these early structural events are related to the biochemical
      pathways that trigger differentiation. We show here that beta-catenin, gamma
      catenin/plakoglobin, and p120-Cas are all significantly tyrosine phosphorylated
      in primary mouse keratinocytes induced to differentiate by calcium, with a time
      course similar to that of cell junction formation. Together with these changes,
      there is an increased association of alpha-catenin and p120-Cas with E-cadherin,
      which is prevented by tyrosine kinase inhibition. Treatment of E-cadherin
      complexes with tyrosine-specific phosphatase reveals that the strength of alpha
      catenin association is directly dependent on tyrosine phosphorylation. In
      parallel with the biochemical effects, tyrosine kinase inhibition suppresses
      formation of cell adhesive structures, and causes a significant reduction in
      adhesive strength of differentiating keratinocytes. The Fyn tyrosine kinase
      colocalizes with E-cadherin at the cell membrane in calcium-treated
      keratinocytes. Consistent with an involvement of this kinase, fyn-deficient
      keratinocytes have strongly decreased tyrosine phosphorylation levels of beta-
      and gamma-catenins and p120-Cas, and structural and functional abnormalities in
      cell adhesion similar to those caused by tyrosine kinase inhibitors. Whereas skin
      of fyn-/- mice appears normal, skin of mice with a disruption in both the fyn and
      src genes shows intrinsically reduced tyrosine phosphorylation of beta-catenin,
      strongly decreased p120-Cas levels, and important structural changes consistent
      with impaired keratinocyte cell adhesion. Thus, unlike what has been proposed for
      oncogene-transformed or mitogenically stimulated cells, in differentiating
      keratinocytes tyrosine phosphorylation plays a positive role in control of cell
      adhesion, and this regulatory function appears to be important both in vitro and
      in vivo.

PMID- 9628902
TI  - Saccharomyces cerevisiae exonuclease-1 plays a role in UV resistance that is
      distinct from nucleotide excision repair.
AB  - Two closely related genes, EXO1 and DIN 7, in the budding yeast Saccharomyces
      cerevisiae have been found to be sequence homologs of the exo1 gene from the
      fission yeast Schizosaccharomyces pombe . The proteins encoded by these genes
      belong to the Rad2/XPG and Rad27/FEN-1 families, which are structure-specific
      nucleases functioning in DNA repair. An XPG nuclease deficiency in humans is one
      cause of xeroderma pigmentosum and those afflicted display a hypersensitivity to
      UV light. Deletion of the RAD2 gene in S. cerevisiae also causes UV
      hypersensitivity, due to a defect in nucleotide excision repair (NER), but
      residual UV resistance remains. In this report, we describe evidence for the
      residual repair of UV damage to DNA that is dependent upon Exo1 nuclease.
      Expression of the EXO1 gene is UV inducible. Genetic analysis indicates that the
      EXO1 gene is involved in a NER-independent pathway for UV repair, as exo1 rad2
      double mutants are more sensitive to UV than either the rad2 or exo1 single
      mutants. Since the roles of EXO1 in mismatch repair and recombination have been
      established, double mutants were constructed to examine the possible relationship
      between the role of EXO1 in UV resistance and its roles in other pathways for
      repair of UV damaged DNA. The exo1 msh2 , exo1 rad51 , rad2 rad51 and rad2 msh2
      double mutants were all more sensitive to UV than their respective pairs of
      single mutants. This suggests that the observed UV sensitivity of the exo1
      deletion mutant is unlikely to be due to its functional deficiencies in MMR,
      recombination or NER. Further, it suggests that the EXO1 , RAD51 and MSH2 genes
      control independent mechanisms for the maintenance of UV resistance.

PMID- 9628903
TI  - The XRCC2 DNA repair gene from human and mouse encodes a novel member of the
      recA/RAD51 family.
AB  - We recently identified a positional candidate for the XRCC2 DNA repair gene at
      human chromosome 7q36.1. We have now cloned the cDNA for this gene from both
      human and mouse and show that it is a highly conserved novel member of the recA /
      RAD51 recombination repair gene family. The cDNA is able to complement
      significantly the phenotype of a unique cell line, irs1 , which shows extreme
      sensitivity to DNA cross-linking agents and genetic instability. Thisphenotype is
      consistent with a role for the XRCC2 gene in recombination repair in somatic
      cells, suggesting that in addition to RAD51 , other members of this gene family
      have an important function in high fidelity repair processes in mammals. Despite
      this function, the XRCC2 gene transcript is expressed at a very low level in
      somatic tissue, but is elevated in mouse testis, suggesting an additional role in
      meiosis.

PMID- 9628905
TI  - A single nucleotide change in the c-myc internal ribosome entry segment leads to
      enhanced binding of a group of protein factors.
AB  - A 340 nucleotide section of the c- myc 5' untranslated region (UTR) contains an
      internal ribosome entry segment. We have described previously a mutation in this
      region of RNA in cell lines derived from patients with multiple myeloma (MM)
      which exhibit increased expression of c- myc protein by an aberrant translational
      mechanism. In this study we show by electrophoretic mobility shift assays (EMSA),
      north-western blotting and UV cross-linking that radiolabelled c- myc 5' UTR RNA
      transcripts which harbour the mutation cause enhanced binding of cellular
      proteins. In addition, we also demonstrate that an MM derived cell line possesses
      an altered repertoire of RNA binding proteins. Our data suggest that the
      deregulated expression of c -myc in MM could result both from the effect of the
      mutation and the additional proteins which are present in these cell types.

PMID- 9628904
TI  - Expression, purification and characterization of the recombinant ribonuclease P
      protein component from Bacillus subtilis.
AB  - Ribonuclease P is a ribonucleoprotein complex that catalyzes the essential 5'
      maturation of all precursor tRNA molecules. The protein component both alters the
      conformation of the RNA component and enhances the substrate affinity and
      specificity. To facilitate biochemical and biophysical studies, the protein
      component of Bacillus subtilis ribonuclease P (RNase P) was overproduced in
      Escherichia coli using the native amino acid sequence with the initial 20 codons
      optimized for expression in E.coli . A simple purification procedure using
      consecutive cation exchange chromatography steps in the presence and absence of
      urea was developed to purify large quantities of P protein without contaminating
      nucleic acids. The identity of the recombinant protein as a cofactor of RNase P
      was established by its ability to stimulate the activity of the RNA component in
      low ionic strength buffer in a 1:1 stoichiometry. Circular dichroism studies
      indicate that P protein is a combination of alpha-helix and beta-sheet secondary
      structures and is quite stable, with a T m of 67 degrees C. The described methods
      facilitated the large scale purification of homogeneous, RNA-free P protein
      required for high resolution crystallographic analyses and may be useful for the
      preparation of other RNA binding proteins.

PMID- 9628906
TI  - The orientation and dynamics of the C2'-OH and hydration of RNA and DNA.RNA
      hybrids.
AB  - The stereochemical and dynamic properties of the C2' hydroxyl group in several
      DNA.RNA hybrids have been measured by NMR and compared with the homologous RNA
      duplex. The C2'-OH NMR signals of the RNA strands were identified, and numerous
      specific assignments were made. The rate constants for exchange of the hydroxyl
      protons with water were determined at 5 degrees C, and were found to depend on
      both the position within a particular sequence and the nature of the duplex. On
      average, the exchange rate constants were slowest for the hybrids of composition
      rR.dY, and fastest for the RNA duplex, with an overall range of approximately 10
      50/s. In the DNA.RNA hybrids, strong NOEs and ROEs were observed between the OH
      and the H1' of the same sugar, unambiguously showing that the OH proton points
      toward the H1' most of the time, and not toward the O3' of the same sugar.
      Evidence for significant hydration in both grooves of the DNA.RNA hybrids and the
      DNA duplex was found in ROESY and NOESY experiments. On average, the minor groove
      of the DNA.RNA hybrids showed more kinetically significant hydration than the
      DNA, which can be attributed to the hydrophilic lining of hydroxyl groups in RNA.

PMID- 9628907
TI  - Prothymosin alpha modulates the interaction of histone H1 with chromatin.
AB  - Prothymosin alpha (ProTalpha) is an abundant acidic nuclear protein that may be
      involved in cell proliferation. In our search for its cellular partners, we have
      recently found that ProTalpha binds to linker histone H1. We now provide further
      evidence for the physiological relevance of this interaction by immunoisolation
      of a histone H1-ProTalpha complex from NIH 3T3 cell extracts. A detailed analysis
      of the interaction between the two proteins suggests contacts between the acidic
      region of ProTalpha and histone H1. In the context of a physiological chromatin
      reconstitution reaction, the presence of ProTalpha does not affect incorporation
      of an amount of histone H1 sufficient to increase the nucleosome repeat length by
      20 bp, but prevents association of all further H1. Consistent with this finding,
      a fraction of histone H1 is released when H1-containing chromatin is challenged
      with ProTalpha. These results imply at least two different interaction modes of
      H1 with chromatin, which can be distinguished by their sensitivity to ProTalpha.
      The properties of ProTalpha suggest a role in fine tuning the stoichiometry
      and/or mode of interaction of H1 with chromatin.

PMID- 9628908
TI  - A highly specific terminal uridylyl transferase modifies the 3'-end of U6 small
      nuclear RNA.
AB  - HeLa cell extracts contain significant amounts of terminal uridylyl transferase
      (TUTase) activity. In a template-independent reaction with labeled UTP, these
      enzymes are capable of modifying a broad spectrum of cellular RNA molecules in
      vitro . However, fractionation of cell extracts by gel filtration clearly
      separated two independent activities. In addition to a non-specific enzyme, an
      additional terminal uridylyl transferase has been identified that is highly
      specific for cellular and in vitro synthesized U6 small nuclear RNA (snRNA)
      molecules. This novel TUTase enzyme was also able to select as an efficient
      substrate U6 snRNA species from higher eucaryotes. In contrast, no labeling was
      detectable with purified fission yeast RNA. Using synthetic RNAs containing
      different amounts of transcribed 3'-end UMP residues, high resolution gel
      electrophoresis revealed that U6 snRNA species with three terminal U nucleotides
      served as the optimal substrate for the transferase reaction. The 3'-end
      modification of the optimal synthetic substrate was identical to that observed
      with endogenous U6 snRNA isolated from HeLa cells. Therefore, we conclude that
      the specific addition of UMP residues to 3'-recessed U6 snRNA molecules reflects
      a recycling process, ensuring the functional regeneration for pre-mRNA splicing
      of this snRNA.

PMID- 9628909
TI  - A comparative study of the thermal stability of oligodeoxyribonucleotides
      containing 5-substituted 2'-deoxyuridines.
AB  - Two series of modified oligonucleotides based on the self-complementary dodecamer
      d(CGCTAATTAGCG) were synthesized. The first contained the -C identical withCCH2R
      linker at C5 of deoxyuridine at position 4 (T*) of d(CGCT*AATTAGCG) and the
      second contained the -SR linker. The goal of the study was to evaluate and
      compare these two types of side chains for suitability as tethers for linking
      reporter groups to oligonucleotides. Our primary concern was how these tethers
      would effect duplex stability. The modified nucleosides were synthesized by
      palladium-mediated coupling reactions between the substituted alkyne and 5'-(4,
      4'-dimethoxytrityl)-5-iodo-2'-deoxyuridine and between a disulfide and 5
      chloromercurio-2'-deoxyuridine. The C5 deoxyuridine side chains evaluated
      included C identical with CCH3, C identical with CCH2NHC(O)CH3, C identical with
      CCH2N(CH3)2, C identical with CCH2N-HC(O)C5H4N, C identical with
      CCH2NHC(O)C10H15, SCH3, SC6H5 and SCH2CH2NHC(O)CH3. The nucleosides containing
      these substituents were incorporated into oligo-deoxyribonucleotides by standard
      phosphoramidite methodology. Melting studies demonstrated that the sequence
      containing the C identical with CCH3side chain had the highest T m value (59.1
      degrees C) in comparison with the control sequence (T m = 55.2 degrees C) and
      that any additional substituent on C3 of the propynyl group lowered the T m value
      relative to propynyl. Nevertheless, even the most destabilizing substituent,
      adamantylcarbamoyl, yielded an oligodeoxyribonucleotide that dissociated with a T
      m of 54 degrees C, which is only 1.2 degrees C less than the control sequence. In
      contrast, the thioether substituents led to lower T m values, ranging from as low
      as 45.1 degrees C for SPh up to 52.2 degrees C for SMe. Replacing the methyl of
      the SMe substituent with a CH2CH2NHC(O)CH3 tether led to no further reduction in
      melting temperature. The T m value of the CH2CH2NHC(O)CH3-containing
      oligonucleotide was less than the natural sequence by 1.6 degrees C/substituent.
      This is sufficiently small that it is anticipated that the C5 thioether linkage
      may be as useful as the acetylenic linkage for tethering reporter groups to
      oligonucleotides. More importantly, the thioether linkage provides a means to
      position functional groups to interact specifically with opposing complementary
      (target) sequences.

PMID- 9628910
TI  - Synthesis and hybridization analysis of a small library of peptide
      oligonucleotide conjugates.
AB  - A small library of 49 peptide-oligonucleotide conjugates were synthesized to
      explore the influence of various peptide side chains on the hybridization
      properties of the DNA. An invariant 8mer oligonucleotide was coupled to a peptide
      portion that contained a five residue variable region composed of the cationic
      amino acids lysine, ornithine, histidine and arginine, the hydrophobic amino acid
      tryptophan, and alanine as a spacer. Melting temperature analysis indicated that
      T m depended principally on the number of cationic residues. The free energies of
      binding for polycationic peptide-oligonucleotides were enhanced compared with the
      unmodified 8mer. The origin of this stabilizing effect was found to be derived
      from a more exothermic enthalpic term. Improvement in Delta G vH was found to
      depend on the presence of positive charge and also the exact identity of the
      cationic amino acid, with the polyarginine peptide giving the most favourable
      Delta G vH value and the most exothermic Delta H vH. Further exploration
      suggested that the cationic peptide fragments interacted mainly with single
      stranded rather than duplex DNA. A study of pH dependence showed that the
      polyhistidine conjugate was particularly sensitive to pH changes near neutrality,
      as indicated by a significant rise in T m from 19.5 degrees C at pH 8.0 to 28.5
      degrees C at pH 6.0.

PMID- 9628911
TI  - XR-C1, a new CHO cell mutant which is defective in DNA-PKcs, is impaired in both
      V(D)J coding and signal joint formation.
AB  - DNA-dependent protein kinase (DNA-PK) plays an important role in DNA double
      strand break (DSB) repair and V(D)J recombination. We have isolated a new X-ray
      sensitive CHO cell line, XR-C1, which is impaired in DSB repair and which was
      assigned to complementation group 7, the group that is defective in the XRCC7 /
      SCID ( Prkdc ) gene encoding the catalytic subunit of DNA-PK (DNA-PKcs).
      Consistent with this complementation analysis, XR-C1 cells lackeddetectable DNA
      PKcs protein, did not display DNA-PK catalytic activity and were complemented by
      the introduction of a single human chromosome 8 (providing the Prkdc gene). The
      impact of the XR-C1 mutation on V(D)J recombination was quite different from that
      found in most rodent cells defective in DNA-PKcs, which are preferentially
      blocked in coding joint formation, whereas XR-C1 cells were defective in forming
      both coding and signal joints. These results suggest that DNA-PKcs is required
      for both coding and signal joint formation during V(D)J recombination and that
      the XR-C1 mutant cell line may prove to be a useful tool in understanding this
      pathway.

PMID- 9628912
TI  - Meiotic role of SWI6 in Saccharomyces cerevisiae.
AB  - The transcript levels of DNA replication genes and some recombination genes in
      Saccharomyces cerevisiae fluctuate and peak at the G1/S boundary in the mitotic
      cell cycle. This fluctuation is regulated by MCB (Mlu I cell cycle box) elements
      which are bound by the DSC1/MBF1 complex consisting of Swi6 and Mbp1. It is also
      known that some of the MCB-regulated genes are induced by treatment with DNA
      damaging agents and in meiosis. In this report, the function of SWI6 in meiosis
      was investigated. Delta swi6 cells underwent sporulation as did wild-type cells.
      However, the deletion mutant cells showed reduced spore viability and lower
      frequency of recombination. The transcript levels of the recombination genes
      RAD51 and RAD54 , which have MCB elements, were reduced in Delta swi6 cells. The
      transcript levels of SWI6 itself were also induced and declined in meiosis.
      Furthermore, an increased dosage of SWI6 enhanced the transcript level of the
      RAD51 gene and also the recombination frequency in meiosis. These results suggest
      that SWI6 enhances the expression level of the recombination genes in meiosis in
      a dosage-dependent manner, which results in an effect on the frequency of meiotic
      recombination.

PMID- 9628913
TI  - Chemical and enzymatic properties of bridging 5'-S-phosphorothioester linkages in
      DNA.
AB  - We describe physicochemical and enzymatic properties of 5' bridging
      phosphorothioester linkages at specific sites in DNA oligonucleotides. The
      susceptibility to hydrolysis at various pH values is examined and no measurable
      hydrolysis is observed at pH 5-9 after 4 days at 25 degrees C. The abilities of
      three 3'- and 5'-exonuclease enzymes to hydrolyze the DNA past this linkage are
      examined and it is found that the linkage causes significant pauses at the sulfur
      linkage for T4 DNA polymerase and calf spleen phosphodiesterase, but not for
      snake venom phosphodiesterase. Restriction endonuclease (Nsi I) cleavage is also
      attempted at a 5'-thioester junction and strong resistance to cleavage is
      observed. Also tested is the ability of polymerase enzymes to utilize templates
      containing single 5'-S-thioester linkages; both Klenow DNA polymerase and T7 RNA
      polymerase are found to synthesize complementary strands successfully without any
      apparent pause at the sulfur linkage. Finally, the thermal stabilities of
      duplexes containing such linkages are measured; results show that T m values are
      lowered by a small amount (2 degrees C) when one or two thioester linkages are
      present in an otherwise unmodified duplex. The chemical stability and
      surprisingly small perturbation by the 5' bridging sulfur make it a good
      candidate as a physical and mechanistic probe for specific protein or metal
      interactions involving this position in DNA.

PMID- 9628914
TI  - Identification and characterization of the RAD51 gene from the ciliate
      Tetrahymena thermophila.
AB  - The RAD51 gene is a eukaryotic homolog of rec A, a critical component in
      homologous recombination and DNA repair pathways in Escherichia coli . We have
      cloned the RAD51 homolog from Tetrahymena thermophila , a ciliated protozoan.
      Tetrahymena thermophila RAD51 encodes a 36.3 kDa protein whose amino acid
      sequence is highly similar to representative Rad51 homologs from other eukaryotic
      taxa. Recombinant Rad51 protein was purified to near homogeneity following
      overproduction in a bacterial expression system. The purified protein binds to
      both single- and double-stranded DNA, possesses a DNA-dependent ATPase activity
      and promotes intermolecular ligation of linearized plasmid DNA. While steady
      state levels of Rad51 mRNA are low in normally growing cells, treatment with UV
      light resulted in a >100-fold increase in mRNA levels. This increase in mRNA was
      time dependent, but relatively independent of UV dose over a range of 1400-5200
      J/m2. Western blot analysis confirmed that Rad51 protein levels increase upon UV
      irradiation. Exposure to the alkylating agent methyl methane sulfonate also
      resulted in substantially elevated Rad51 protein levels in treated cells, with
      pronounced localization in the macronucleus. These data are consistent with the
      hypothesis that ciliates such as T.thermophila utilize a Rad51-dependent pathway
      to repair damaged DNA.

PMID- 9628915
TI  - Caged RNA: photo-control of a ribozyme reaction.
AB  - We report here the first photo-chemical control of a ribozyme reaction by the
      site-specific modification of the 2'-hydroxyl nucleophile in the hammerhead
      system with a caging functionality. Rapid laser photolysis of the O-(2
      nitrobenzyl) caging group initiates an efficient and accurate hammerhead
      catalyzed cleavage of substrate RNA under native conditions. RNAs in which
      reactive functionalities or recognition elements are caged in this manner will be
      useful tools to probe RNA reactivity and dynamics.

PMID- 9628916
TI  - Functional analysis of the interaction between HCV 5'UTR and putative subunits of
      eukaryotic translation initiation factor eIF3.
AB  - Translation initiation in Hepatitis C Virus is controlled by the presence of an
      internal ribosome entry site element (IRES) principally located in its 5'
      untranslated region (UTR). Mutation/deletion analyses have shown that the
      integrity of this structure is essential for initiation of cap-independent
      protein synthesis. We have developed a strategy to swap the position of the two
      major domains (II and III) on the 5'UTR sequence. The aim was to further
      characterize this mechanism by preserving domain-specific interactions but
      possibly losing contacts that require any interdomain geometry. The expression of
      dicistronic mRNAs containing these different UTRs showed that the positioning of
      the different domains on the 5'UTR is essential for efficient IRES functioning.
      We then used these mutants to identify cellular factors implicated in IRES
      activity. Using UV crosslinking assays we found that domain III makes direct
      contact with two proteins (p170/p120) which can be associated with efficient IRES
      activity. In particular, we have mapped the binding sites of these proteins and
      shown that p120 binds to the apical loop segment of domain III, whilst p170 binds
      in the stem portion, independently of domain III position or context. Finally, we
      provide evidence showing that p170 and p120 represent two subunits of eukaryotic
      initiation factor eIF3: p170 and p116/p110.

PMID- 9628917
TI  - Gene length and codon usage bias in Drosophila melanogaster, Saccharomyces
      cerevisiae and Escherichia coli.
AB  - The relationship between gene length and synonymous codon usage bias was
      investigated in Drosophila melanogaster, Escherichia coli and Saccharomyces
      cerevisiae. Simulation studies indicate that the correlations observed in the
      three organisms are unlikely to be due to sampling errors or any potential bias
      in the methods used to measure codon usage bias. The correlation was
      significantly positive in E.coli genes, whereas negative correlations were
      obtained for D. melanogaster and S.cerevisiae genes. When only ribosomal protein
      genes were used, whose expression levels are assumed to be similar, E.coli and
      S.cerevisiae showed significantly positive correlations. For the two eukaryotes,
      the distribution of effective number of codons was different in short genes (300
      500 bp) compared with longer genes; this was not observed in E.coli. Both
      positive and negative correlations can be explained by translational selection.
      Energetically costly longer genes have higher codon usage bias to maximize
      translational efficiency. Selection may also be acting to reduce the size of
      highly expressed proteins, and the effect is particularly pronounced in
      eukaryotes. The different relationships between codon usage bias and gene length
      observed in prokaryotes and eukaryotes may be the consequence of these different
      types of selection.

PMID- 9628918
TI  - A novel assay of 8-oxo-2'-deoxyguanosine 5'-triphosphate pyrophosphohydrolase (8
      oxo-dGTPase) activity in cultured cells and its use for evaluation of cadmium(II)
      inhibition of this activity.
AB  - 8-Oxo-2'-deoxyguanosine 5'-triphosphate (8-oxo-dGTP) is a product of oxidative
      modification of dGTP, thatcan be misincorporated into DNA, causing AT-->CG
      mutations. Cells are protected against 8-oxo-dGTP by 8-oxo-dGTP 5'
      pyrophosphohydrolases (8-oxo-dGTP-ases) that convert it to 8-oxo-dGMP. Thus,
      inhibition of 8-oxo-dGTPases may lead to cancer. To elucidate the involvement of
      8-oxo-dGTPases in carcinogenesis, an assay of the 8-oxo-dGTPase activity is
      required. This paper presents such an assay developed for Chinese hamster ovary
      (CHO) cells that can be applied to any biological material. It includes: (i) a
      convenient method for preparing 8-oxo-2'-deoxyguanosine 5'-phosphates; (ii) an
      HPLC/UV quantification of 8-oxo-dGTP hydrolysis products and (iii) separation of
      8-oxo-dGTPase activity from interfering 8-oxo-dGTP phosphatase(s). The 8-oxo
      dGTPase activity of CHO cells depends on magnesium, has a pH optimum of 8.5, Km
      for 8-oxo-dGTP of 9.3 microM, and is inhibited by 8-oxo-dGDP, the product of
      interfering 8-oxo-dGTP phosphatases. The latter must be removed from the assayed
      samples by ultrafiltration through 30 kDa cut-off membranes. The method was used
      to test the inhibition by cadmium ions of the activity of 8-oxo-dGTPase in CHO
      cells. The cells cultured with 0.3-3 microM cadmium(II) acetate for up to 24 h
      had their 8-oxo-dGTPase activity suppressed in a Cd(II) concentration-dependent
      manner, down to 70% of the control value.

PMID- 9628919
TI  - U2 and U6 snRNA genes in the microsporidian Nosema locustae: evidence for a
      functional spliceosome.
AB  - The removal of introns from pre-messenger RNA is mediated by the spliceosome, a
      large complex composed of many proteins and five small nuclear RNAs (snRNAs). Of
      the snRNAs, the U6 and U2 snRNAs are the most conserved in sequence, as they
      interact extensively with each other and also with the intron, in several base
      pairings that are necessary for splicing. We have isolated and sequenced the
      genes encoding both U6 and U2 snRNAs from the intracellularly parasitic
      microsporidian Nosema locustae . Both genes are expressed. Both RNAs can be
      folded into secondary structures typical of other known U6 and U2 snRNAs. In
      addition, the N.locustae U6 and U2 snRNAs have the potential to base pair in the
      functional intermolecular interactions that have been characterized by extensive
      analyses in yeast and mammalian systems. These results indicate that the
      N.locustae U6 and U2 snRNAs may be functional components of an active
      spliceosome, even though introns have not yet been found in microsporidian genes.

PMID- 9628920
TI  - Cap ribose methylation of c-mos mRNA stimulates translation and oocyte maturation
      in Xenopus laevis.
AB  - In Xenopus oocytes, progesterone stimulates the cytoplasmic polyadenylation and
      resulting translational activation of c-mos mRNA, which is necessary for the
      induction of oocyte maturation. Although details of the biochemistry of
      polyadenylation are beginning to emerge, the mechanism by which 3' poly(A)
      addition stimulates translation initiation is enigmatic. A previous report showed
      that polyadenylation induced cap-specific 2'-O-methylation, and suggested that
      this 5' end modification was important for translational activation. Here, we
      demonstrate that injected c-mos RNA undergoes polyadenylation and cap ribose
      methylation. Inhibition of this methylation by S-isobutylthioadenosine (SIBA), a
      methyltransferase inhibitor, has little effect on progesterone-induced c-mos mRNA
      polyadenylation or general protein synthesis, but prevents the synthesis of Mos
      protein as well as oocyte maturation. Maturation can be rescued, however, by the
      injection of factors that act downstream of Mos, such as cyclin A and B mRNAs.
      Most importantly, we show that the translational efficiency of injected mRNAs
      containing cap-specific 2'-O-methylation (cap I) is significantly enhanced
      compared to RNAs that do not contain the methylated ribose (cap 0). These results
      suggest that cap ribose methylation of c-mos mRNA is important for translational
      recruitment and for the progression of oocytes through meiosis.

PMID- 9628921
TI  - Influence of promoter potency on the transcriptional effects of YY1, SRF and Msx
      1 in transient transfection analysis.
AB  - Potent viral promoters/enhancers are often used to achieve high level expression
      of ectopic genes in transient transfection analysis. By using a GAL4-responsive
      transcription assay system, we show that the use of potent eukaryotic expression
      vectors can lead to biased transcriptional effects. Three functionally diverse
      transcription factors, YY1, SRF and Msx-1, were examined and each was found to
      exhibit a strong transrepression function in the context of the DNA binding
      domain of GAL4 when expressed from the cytomegalovirus (pCMV) or simian virus 40
      (pSV) promoters/enhancers. An internal 15 amino acid domain of YY1 mediating
      transrepression in the viral promoter setting was identified. This GAL4-mediated
      transcriptional repression could, however, be completely relieved by using the
      yeast alcohol dehydrogenase promoter (pADH) to drive gene expression, which is
      approximately 100-fold weaker than canonical pCMV and pSV in cultured mammalian
      cells. In addition, low level expression achieved with the pADH vector unveiled
      the intrinsic transactivation functions of YY1 and SRF previously not observed
      with the GAL4 assay system. Our results highlight a potential pitfall in
      conventional pCMV- and pSV-based transfection assays and suggest that the use of
      a low level expression system may be preferable in most transcriptional analysis.

PMID- 9628922
TI  - Forum domain in Drosophila melanogaster cut locus possesses looped domains
      inside.
AB  - We have studied the relationship between chromosomal forum domains and looped
      domains in the cut locus of Drosophila melanogaster . Forum domains were earlier
      detected by separation in pulsed-field gels of 50-150 kb chromosomal DNA
      fragments obtained after spontaneous non-random degradation of chromosomes. We
      have localized the boundary region where cleavage sites are scattered between two
      forum domains in the regulatory region of the cut locus. We have sequenced a 13
      kb region spanning few kilobases from distal domain, the boundary region and part
      of the proximal forum domain where several scaffold associated regions (SARs)
      were observed. We conclude that forum domains and looped domains are physically
      different types of domains and belong to different levels of organization in
      eukaryotic chromosomes. The boundary region between the neighboring forum domains
      in the cut locus possesses the Doc element insertion and a micro-satellite
      stretch and thus might remind a small island of heterochromatin and correspond to
      so-called intercalary heterochromatin that is known to be located in the 7B1-2
      band where the major part of the cut locus is reside.

PMID- 9628923
TI  - The observation of the local ordering characteristics of spermidine-condensed
      DNA: atomic force microscopy and polarizing microscopy studies.
AB  - Condensation of DNA by multivalent cations can provide useful insights into the
      physical factors governing the folding and packaging of DNA in vivo. In this
      work, local ordered structures of spermidine-DNA complexes prepared from
      different DNA concentrations have been examined by using atomic force microscopy
      (AFM) and polarizing microscopy (PM). Two types (I and II) of DNA condensates,
      significantly different in sizes, were observed. It was found that for extremely
      dilute solutions (DNA concentrations around 1 ng/microl or below), the DNA
      molecules would collapse into toroidal structures with a volume equivalent to a
      single lambda-DNA (type I). In relatively dilute solutions (DNA concentrations
      between 1 and 10 ng/microll), a significantly larger structure of multimolecular
      toroids (circular and elliptical, type II) were formed, which were constructed by
      many fine particles. Measurements show that the average diameter of these fine
      particles was similar to the outer diameter of the monomolecular toroids observed
      in extremely dilute solutions, and the thickness of the multimolecular toroids
      had a distribution of multi-layers with height increments of 11 nm, indicating
      that the multimolecular toroidal structures have lamellar characteristics.
      Moreover, by enriching the DNA-spermidine complexes in very diluted solution,
      branch-like structures constructed by subunits were observed by using AFM. The
      analysis of the pellets in polarizing microscopy reveals a liquid-crystal-like
      pattern. These observations suggest that DNA-spermidine condensation could have
      multiple stages, which are very sensitive to the DNA and spermidine
      concentrations.

PMID- 9628925
TI  - Long-range translational coupling in single-stranded RNA bacteriophages: an
      evolutionary analysis.
AB  - In coliphage MS2 RNA a long-distance interaction (LDI) between an internal
      segment of the upstream coat gene and the start region of the replicase gene
      prevents initiation of replicase synthesis in the absence of coat gene
      translation. Elongating ribosomes break up the repressor LDI and thus activate
      the hidden initiation site. Expression studies on partial MS2 cDNA clones
      identified base pairing between 1427-1433 and 1738-1744, the so-called Min Jou
      (MJ) interaction, as the molecular basis for the long-range coupling mechanism.
      Here, we examine the biological significance of this interaction for the control
      of replicase gene translation. The LDI was disrupted by mutations in the 3'-side
      and the evolutionary adaptation was monitored upon phage passaging. Two
      categories of pseudorevertants emerged. The first type had restored the MJ
      interaction but not necessarily the native sequence. The pseudorevertants of the
      second type acquired a compensatory substitution some 80 nt downstream of the MJ
      interaction that stabilizes an adjacent LDI. In one examined case we confirmed
      that the second site mutations had restored coat-replicase translational
      coupling. Our results show the importance of translational control for fitness of
      the phage. They also reveal that the structure that buries the replicase start
      extends to structure elements bordering the MJ interaction.

PMID- 9628924
TI  - Generation of circular RNAs and trans-cleaving catalytic RNAs by rolling
      transcription of circular DNA oligonucleotides encoding hairpin ribozymes.
AB  - A simple new strategy for the in vitro synthesis of circular RNAs and hairpin
      ribozymes is described. Circular single-strand DNA oligonucleotides 67-79 nt in
      length are constructed to encode both hairpin ribozyme sequences and ribozyme
      cleavable sequences. In vitro transcription of these small circles by Escherichia
      coli RNA polymerase produces long repeating RNAs by a rolling circle mechanism.
      These repetitive RNAsundergo self-processing, eventually yielding unit length
      circular and linear RNAs as the chief products. The transcription is efficient
      despite the absence of promoter sequences, with RNA being produced in up to 400
      times the amount of DNA circle used. It is shown that the linear monomeric
      hairpin ribozymes are active in cleaving RNA targets in trans , including one
      from HIV-1. Several new findings are established: (i) that rolling circle
      transcription can be extended to the synthesis of catalytic RNAs outside the
      hammerhead ribozyme motif; (ii) that rolling circle transcription is potentially
      a very simple and useful strategy for the generation of circular RNAs in
      preparative amounts; and (iii) that self-processed hairpin ribozymes can be
      catalytically active in trans despite the presence of self-binding domains.

PMID- 9628927
TI  - Multilevel regulation of histone gene expression during the cell cycle in tobacco
      cells.
AB  - The respective involvement of transcriptional and post-transcriptional mechanisms
      in coupling H3 and H4 histone gene expression to the S phase of the cell cycle
      has been studied in synchronized tobacco cells. Induction of histone gene
      expression at the G1/S transition is shown to be essentially directed by an
      increase in the transcription rate in response to cellular signals occurring at
      the initiation step of DNA replication. Histone gene induction thus precedes the
      burst of DNA synthesis. However, when the elongation step of DNA replication is
      ineffective or artificially arrested, feedback mechanisms apparently act at the
      translation level to avoid overproduction of histone proteins from their mRNAs.
      At the end of S phase, post-transcriptional mechanisms ensure a rapid degradation
      of histone mRNAs. Transcription factors are bound to the cis -elements of histone
      promoters throughout the cell cycle, thus suggesting a post-translational
      modification of some of them to trigger promoter activation at the G1/S
      transition. Based on these results, a model is proposed for histone gene
      transcriptional induction in connection with the components of the cell cycle
      machinery.

PMID- 9628926
TI  - Genetic characterisation of hda1+, a putative fission yeast histone deacetylase
      gene.
AB  - hda1+ (histone deacetylase 1) is a fission yeast gene which is highly similar in
      sequence to known histone deacetylase genes in humans and budding yeast. We have
      investigated if this putative histone deacetylase contributes to transcriptional
      silencing in the fission yeast Schizosaccharomyces pombe. A precise deletion
      allele of the hda1+ open reading frame was created. Cells lacking the hda1+ gene
      are viable. However, genetic analysis reveals that cells without hda1 + display
      enhanced gene repression/silencing of marker genes, residing adjacent to
      telomeres, close to the silent mating-type loci and within centromere I. This
      phenotype is very similar to that recently reported for rpd3 mutants both in
      Drosophila and budding yeast. No defects in chromosome segregation or changes in
      telomere length were detected. Cells lacking the hda1+ gene display reduced
      sporulation. Growth of hda1 cells is partially inhibited by low concentrations of
      Trichostatin A (TSA), a known inhibitor of histone deacetylase enzymes. TSA
      treatment is also able to overcome the enhanced silencing found in
      heterochromatic regions of hda1 cells. These results indicate a genetic
      redundancy with respect to deacetylase genes and partially overlapping functions
      of these in fission yeast. The significance of these results is discussed in the
      light of recent discoveries from other eukaryotes.

PMID- 9628928
TI  - Inducible expression based on regulated recombination: a single vector strategy
      for stable expression in cultured cells.
AB  - When fused to the ligand binding domain (LBD) of steroid hormone nuclear
      receptors, site-specific recombinases (SSRs) acquire a ligand-dependent activity.
      Here, we describe the use of SSR-LBD fusion proteins in an inducible expression
      system, introduced into cells in a single step. A single transgene contains a
      constitutively active, bi-directional enhancer/promoter, which directs
      expression, on one side, of an SSR-LBD fusion protein gene and, on the other, a
      selectable marker/inducible gene cassette. The selectable marker, the puromycin
      acetyltransferase (pac) gene, is used for stable genomic integration of the
      transgene and is flanked by recombination target sites. The inducible gene is not
      expressed because the pac gene lies between it and the promoter. Activation of
      the SSR-LBD by a ligand induces recombination and the pac gene is excised. The
      inducible gene is thus positioned next to the promoter and so is expressed. This
      describes a ligand-inducible expression strategy that relies on regulated
      recombination rather than regulated transcription. By inducible expression of
      diptheria toxin, evidence that this system permits inducible expression of very
      toxic proteins is presented. The combination of the complete regulatory circuit
      and inducible gene in one transgene relates expression of the selectable marker
      gene to expression from the bi-directional enhancer/promoter. We exploit this
      relationship to show that graded increases in selection pressure can be used to
      select for clones with different induction properties.

PMID- 9628929
TI  - Co-packaging of sense and antisense RNAs: a novel strategy for blocking HIV-1
      replication.
AB  - Retroviral vectors were engineered to express either sense (MoTiN-TRPsie+) or
      sense and antisense (MoTN-TRPsie+/-) RNAs containing the human immunodeficiency
      virus type-1 (HIV-1) trans -activation response (TAR) element and the extended
      packaging (Psie) signal. The Psie signal includes the dimer linkage structure
      (DLS) and the Rev response element (RRE). Amphotropic vector particles were used
      to transduce a human CD4+ T-lymphoid (MT4) cell line. Stable transductants were
      then tested for sense and antisense RNA production and susceptibility to HIV-1
      infection. HIV-1 production was significantly decreased in cells transduced with
      MoTiN-TRPsie+ and MoTN-TRPsie+/-vectors. Efficient packaging of sense and most
      remarkably of antisense RNA was observed within the virus progeny. Infectivity of
      this virus was significantly decreased in both cases, suggesting that the
      interfering RNAs were co-packaged with HIV-1 RNA. Vector transduction was not
      expected to occur and was not observed. Inhibition of HIV-1 replication was also
      demonstrated in human peripheral blood lymphocytes transduced with retroviral
      vectors expressing antisense RNA. These results suggest that (i) both sense and
      antisense RNAs were co-packaged with HIV-1 RNA, (ii) the co-packaged sense and
      antisense RNAs inhibited virus infectivity and (iii) the co-packaged sense and
      antisense RNAs were not transduced. Sense and antisense RNA-based strategies may
      also be used to co-package other interfering RNAs (e.g. ribozymes) to cleave HIV
      1 virion RNA.

PMID- 9628930
TI  - Complete sequence of the amphioxus (Branchiostoma lanceolatum) mitochondrial
      genome: relations to vertebrates.
AB  - The complete nucleotide sequence of the mitochondrial DNA of the amphioxus
      Branchiostoma lanceolatum has been determined. This mitochondrial genome is small
      (15 076 bp) because of the short size of the two rRNA genes and the tRNA genes.
      In addition, this genome contains a very short non-coding region (57 bp) with no
      sequence reminiscent of a control region. The organisation of the coding genes,
      as well as of the two rRNA genes, is identical to that of the sea lamprey. Some
      differences in the repartition of the tRNA genes occur when compared to the
      lamprey. The mitochondrial codon usage of the amphioxus is reminiscent of that of
      urochordates since the AGA codon is read as a glycine and not as a stop codon as
      in vertebrates. Moreover, the base composition at the wobble positions of the
      codon is strongly biased toward guanine. Altogether, these data clearly emphasise
      the close relationships between amphioxus and vertebrates, and reinforce the
      notion that prochordates may be viewed as the brother group of vertebrates.

PMID- 9628931
TI  - A mutation in NPS1/STH1, an essential gene encoding a component of a novel
      chromatin-remodeling complex RSC, alters the chromatin structure of Saccharomyces
      cerevisiae centromeres.
AB  - The NPS1/STH1 gene encodes a nuclear protein essential for the progression of
      G2/M phase in Saccharomyces cerevisiae . Nps1p shares homology to Snf2/Swi2p, a
      subunit of a protein complex known as the SNF/SWI complex. Recently, Nps1p was
      found to be a component of a protein complex termed RSC (3) essential for mitotic
      growth, whereas its function is unknown. We isolated a temperature-sensitive
      mutant allele of NPS1 , nps1-105, and found that the mutation increases the
      sensitivity to thiabendazole (TBZ). At the restrictive temperature, nps1-105
      arrested at the G2/M phase in MAD1-dependent manner and missegregated the mini
      chromosome with higher frequency than the wild type cells. The nuclease digestion
      of the chromatin of the mutant cells revealed that the mutation causes the
      alteration of the chromatin structure around centromeres at the restrictive
      temperature. The results suggested that, in the nps1-105 mutant, impaired
      chromatin structure surrounding centromeres may lead to an impairment of
      kinetochore function and the cells arrest at G2/M phase through the spindle
      assembly checkpoint system.

PMID- 9628932
TI  - Regenerating livers of old rats contain high levels of C/EBPalpha that correlate
      with altered expression of cell cycle associated proteins.
AB  - The nuclear transcription factor, CCAAT/enhancer binding protein alpha
      (C/EBPalpha) is expressed at high levels in the liver and inhibits growth in
      cultured cells. We have tested the correlation between C/EBPalpha levels, cell
      cycle proteins and hepatocyte proliferation in old and young animals as an in
      vivo model system in which the proliferative response to partial hepatectomy (PH)
      has been shown to be reduced and delayed in old animals. Here we present evidence
      that the expression of C/EBPalpha in old rats (24 months) differs from its
      expression in young animals (6-10 months) during liver regeneration. Induction of
      proliferating cell nuclear antigen (PCNA), a marker of DNA synthesis, occurs at
      24 h after PH in young rats but is delayed and reduced in old animals. Induction
      of the mitotic-specific protein, cdc2 p34, is 3-4-fold less in regenerating liver
      of old rats than in the liver of young animals, confirming the reduced
      proliferative response in old animals. In young rats, the normal regenerative
      response involves a reduction of 3-4-fold in the levels of C/EBPalpha protein at
      3-24 h. In old animals, C/EBPalpha is not reduced within 24 h after PH, but a
      decrease of C/EBPalpha protein levels can be detected at 72 h after PH. Induction
      of C/EBPbeta, another member of the C/EBP family, is delayed in old animals.
      Changes in the expression of C/EBP proteins are accompanied by alteration of the
      CDK inhibitor, p21, which is also decreased in young rats after PH, but in old
      animals remains unchanged. High levels of p21 protein in older animals correlate
      with the lack of cdk2 activation. We suggest that the failure to reduce the
      amount of C/EBPalpha and p21 is a critical event in the dysregulation of
      hepatocyte proliferation in old animals following PH.

PMID- 9628933
TI  - Template-directed photoligation of oligodeoxyribonucleotides via 4-thiothymidine.
AB  - Non-enzymatic, template-directed ligation of oligonucleotides in aqueous solution
      has been of great interest because of its potential synthetic and biomedical
      utility and implications for the origin of life. Though there are many methods
      for template-directed chemical ligation of oligonucleotides, there are only three
      reported photochemical methods. In the first report, template-directed
      photoligation was effected by cyclobutane dimer formation between the 5'- and 3'
      terminal thymidines of two oligonucleotides with >290 nm light, which also
      damages DNA itself. To make the photochemistry of native DNA more selective, we
      have replaced the thymidine at the 5'-end of one oligonucleotide with 4
      thiothymidine (s4T) and show that it photoreacts at 366 nm with a T at the 3'
      endof another oligonucleotide in the presence of a complementary template. When a
      single mismatch is introduced opposite either the s4T or its adjoining T, the
      ligation efficiency drops by a factor of five or more. We also show that by
      linking the two ends of the oligonucleotides together, photoligation can be used
      to form circular DNA molecules and to 'photopadlock' circular DNA templates.
      Thus, s4T-mediated photo-ligation may have applications to phototriggered
      antisense-based or antigene-based genetic tools, diagnostic agents and drugs,
      especially for those situations in which chemical or enzyme-mediated ligation
      isundesirable or impossible, for example inside a cell.

PMID- 9628934
TI  - Biologically-generated primer for PCR: PCR primer of unknown sequence.
AB  - We describe a method for producing specific PCR primers directly from PCR
      product, bypassing the usual need to know the primer sequence. Lack of abundance
      of primers derived from a PCR product is compensated for by the incorporation of
      an arbitrary 5'TAG sequence which acts as a surrogate template target for the
      bulk amplification phase. We use the technique to amplify clonospecific
      rearranged immunoglobulin genes, which have applications as markers of lymphoid
      neoplasms for tracing the success of therapy. The principle may have wider
      application wherever conserved and variable regions of DNA are juxtaposed.

PMID- 9628935
TI  - Efficient removal of PCR inhibitors using agarose-embedded DNA preparations.
AB  - The use of agarose blocks containing embedded DNA improves the PCR amplification
      from templates naturally contaminated with polysaccharides or humic acids, two
      powerful PCR inhibitors. Presumably, the difference in size between the DNA
      macromolecules and these contaminants allows their effective removal from the
      agarose blocks by diffusion during the washing steps, whereas genomic DNA remains
      trapped within them. In addition, agarose-embedded DNA can be directly used for
      PCR since low melting point agarose does not interfere with the reaction. This
      simple and inexpensive method is also convenient for genomic DNAs extracted by
      other procedures, and it is potentially useful for samples containing other kinds
      of soluble inhibitors, overcoming this important problem of current amplification
      techniques.

PMID- 9628936
TI  - One-step affinity purification protocol for human telomerase.
AB  - Human telomerase is a ribonucleoprotein (RNP) enzyme, comprising protein
      components and an RNA template that catalyses telomere elongation through the
      addition of TTAGGG repeats. Telomerase function has been implicated in aging and
      cancer cell immortalization. We report a rapid and efficient one-step
      purification protocol to obtain highly active telomerase from human cells. The
      purification is based on affinity chromatography of nuclear extracts with
      antisense oligonucleotides complementary to the template region of the human
      telomerase RNA component. Bound telomerase is eluted with a displacement
      oligonucleotide under mild conditions. The resulting affinity-purified telomerase
      is active in PCR-amplified telomerase assays. The purified telomerase complex has
      a molecular mass of approximately 550 kDa compared to the approximately 1000 kDa
      determined for the telomerase RNP in unfractionated nuclear extracts. The
      purification protocol provides a rapid and efficient tool for functional and
      structural studies of human telomerase.

PMID- 9628937
TI  - Tailing cDNAs with terminal deoxynucleotidyl transferase in RT-PCR assays to
      identify ribozyme cleavage products.
AB  - Polytailing a cDNA with terminal deoxynucleotidyltransferase (TdT) results in the
      addition of a homopolymeric sequence at its 3'-end. Here we describe the use of
      tailing in competitive RT-PCR assays to evaluate cleavage efficiency of
      ribozymes. Using a system that perfectly mimics intracellular cleavage, we were
      able to detect as few as 1% of cleaved moieties. Furthermore, employing primers
      overlapping the junction between tails and the cleaved RNA moiety in non
      competitive assays, the sensitivity of the method could be improved to <10 fg.
      Using the latter protocol and reactions employing a trans -acting hairpin
      ribozyme targeting the nucleocapsid mRNA of the mumps virus, we were able to
      demonstrate ribozyme-induced cleavage.

PMID- 9628938
TI  - A rapid, small scale method for characterization of plasmid insertions in the
      Dictyostelium genome.
AB  - A rapid, simple method for characterization of plasmid insertions in the
      Dictyostelium discoideum genome was developed. It is based on the capability of
      linear plasmid multimers in the insertions to recircularize efficiently in
      Escherichia coli cells. This recombinational recircularization of plasmid
      multimers provides a highly sensitive and reliable tool for determining whether
      individual Dictyostelium transformants resulted from restriction enzyme-mediated
      integration (REMI) or from recombinational integration of plasmid (RIP). The
      method also reveals any rearrangements in RIP insertions and provides an estimate
      of the vector copy number in any particular transformant.

PMID- 9628939
TI  - Macrokines:invertebrate cytokine-like molecules?
AB  - My laboratory is applying contemporary techniques of biochemistry and molecular
      biology to an important emerging field in biomedicine: the evolution of the
      immune system. Our investigations will build upon the discoveries that key
      immunoregulatory molecules (i.e., cytokines), that function in the mammalian
      immune response appear to be present in phylogenetically distinct invertebrate
      species. Herein, we propose the term macrokine to describe invertebrate proteins
      that have vertebrate cytokine-like activities. The wide distribution of such
      basic elements of innate host defense responses demonstrates its antiquity in
      animal evolution. Through these studies we hope to identify the more ancient
      facets of the vertebrate innate immune response. In turn, these observations may
      help clarify host defense functions and responses not yet appreciated in the
      vertebrate immune system.

PMID- 9628940
TI  - Anatomy and physiology of pediatric swallowing disorders.
AB  - The anatomy and physiology of the act of swallowing is complex. Because the
      swallowing mechanism matures with age, it is important to understand this
      maturation process from neonate to older child to appreciate the impact of this
      changing physiology on pediatric swallowing disorders. This article reviews the
      relevant anatomy, neurologic control mechanism, and physiology of swallowing in
      neonates and children.

PMID- 9628941
TI  - Evaluation of swallowing disorders in children.
AB  - Congenital anomalies of the head and neck and congenital and acquired
      neuromuscular disorders in children are frequently associated with dysfunctional
      feeding and swallowing. Determination of the affected phase of swallowing and
      appropriate guidelines for feeding depend on detailed clinical assessment at the
      bedside and radiographic evaluation by videofluoroscopy. Fiberoptic and rigid
      endoscopic examination of the airway are useful in the diagnosis of subtle
      structural abnormalities that are not appreciated on physical and radiologic
      examination. Once a diagnosis is established, repeating the evaluation process
      helps to assess the outcome of therapeutic and surgical intervention.

PMID- 9628942
TI  - Gastroesophageal reflux in children.
AB  - Gastroesophageal reflux (GER) is a common disorder in infants and children with a
      high rate of spontaneous resolution. Some children, however, will continue to
      have problems and progress from functional GER to pathogenic GER. In children
      with functional GER, diagnostic testing and pharmacologic treatment is
      unnecessary. In more involved cases, there are a number of tests available that
      help to quantify and qualify the extent of disease. Treatment begins with
      conservative measures and progresses to acid neutralization/supression and
      medications to enhance motility. Should medical management fail to control the
      consequences of reflux disease, surgical intervention is warranted.

PMID- 9628943
TI  - Differential diagnosis of dysphagia in children.
AB  - Dysphagia in children often presents a difficult diagnostic challenge. A
      systematic approach in each individual can help with diagnosis and treatment. An
      overview of the differential diagnosis and the diagnostic and treatment options
      available is provided.

PMID- 9628944
TI  - Management of pediatric dysphagia.
AB  - Decisions for management of feeding and swallowing problems in infants and
      children are likely to be most effective in a professional team approach with
      caregivers. Optimal management relies on optimal assessment. This article focuses
      on management strategies that involve "food rules," the position and posture
      changes, alterations in food and liquid attributes, oral-motor and swallow
      function, utensil changes, adjustments in feeding schedules and pacing, and
      behavioral intervention with failure to thrive in the context of global issues
      for children who are oral and nonoral feeders.

PMID- 9628945
TI  - Anatomy and physiology of swallowing in adults and geriatrics.
AB  - Key anatomic and physiologic features that play an important role in normal and
      abnormal swallowing in the adult are described. Highlighted topics include the
      neurologic afferent and efferent control mechanisms, the effect of stroke on
      these mechanisms, and the upper and lower esophageal sphincters.

PMID- 9628946
TI  - Contemporary diagnosis of the dysphagic patient.
AB  - A variety of tests are available to aid in the diagnosis and management of
      dysphagia. In this article the advantages and disadvantages of many of these
      tests are described. Special attention is given to the videoendoscopic swallowing
      study (VESS). An overall treatment plan is described.

PMID- 9628947
TI  - Dysphagia caused by neurologic deficits.
AB  - This article provides a brief review of the neurophysiology behind the normal
      swallow. The examination and work-up of a patient with dysphagia is then
      detailed. Finally, the major neurologic conditions associated with dysphagia are
      considered.

PMID- 9628948
TI  - Systemic causes of dysphagia in adults.
AB  - Dysphagia is associated with many systemic disorders. This article presents
      information that can be used to assist with developing a differential diagnosis
      in patients who have dyshpagia without an obvious localized cause. The essentials
      of the history, physical examination, endoscopy, and special tests are outlined.

PMID- 9628949
TI  - Surgical therapy for swallowing disorders.
AB  - In a physiologic act as complex as swallowing, there are myriad causes of
      dysfunction that can disorder feeding and respiration with grave consequences.
      The appropriate diagnostic evaluation of dysphagia and aspiration along with a
      review of a range of surgical strategies to correct swallowing and aspiration
      disorders are presented in this article.

PMID- 9628950
TI  - Swallowing therapy in adults.
AB  - Swallowing therapy can in many cases eliminate, and in nearly all cases, improve
      swallowing difficulty in adults. A wide variety of faciliatory and compensatory
      techniques are available to therapists who must be specially trained in such
      methods. In addition, swallowing therapy cannot be thought of as a series of
      "lessons" for a patient, but rather a management strategy using a
      multidisciplinary team, including the family of the patient. Efficacy studies are
      becoming available to evaluate the effectiveness of the many therapy methods
      available, and new techniques are constantly being developed and tested. The
      outlook for most adults with swallowing problems is thus optimistic for
      improvement.

PMID- 9628951
TI  - Tobacco and lung cancer.
AB  - Cigarette smoking is responsible for enormous health consequences. Lung cancer is
      fatal in over 80% of cases, and effective treatment is limited. The medical
      impact of cigarette smoking will diminish with effective measures to prevent
      smoking and nicotine addiction and to promote smoking cessation. Efforts should
      focus on the teenage population, with a combination of social, economic, and
      legislative interventions.

PMID- 9628952
TI  - Screening for colorectal cancer.
AB  - Randomized, controlled trials have shown with certainty that screening for
      colorectal cancer reduces morbidity and is cost-effective. Factors that increase
      the risk of colorectal cancer include a personal or family history of adenomatous
      polyps or colorectal cancer, certain genetic syndromes and chronic inflammatory
      bowel disease.

PMID- 9628953
TI  - Breast cancer.
AB  - Infiltrating ductal carcinoma is the most common form of breast cancer, and major
      risk factors are nonmodifiable. Current screening recommendations offer the best
      chance of early diagnosis. Staging takes into account the size of primary tumor,
      number of positive lymph nodes at surgery, and location of distant metastases.
      Treatment options include various combinations of surgical procedures,
      radiotherapy, chemotherapy, and endocrine therapy.

PMID- 9628954
TI  - Pediatric brain tumors.
AB  - Brain tumors are the most common solid neoplasms in childhood. This article
      reviews the current classification, clinical presentations, diagnostic
      procedures, and principles of treatment of pediatric brain tumors. The specific
      presentation, treatment, and prognosis of the most common, individual types of
      pediatric brain tumors are discussed.

PMID- 9628955
TI  - Progress in nuclear medicine imaging of cancers.
AB  - Nuclear imaging is assuming an increasing role in the management of patients with
      cancer. A variety of new radiopharmaceuticals, several antibody or peptide based,
      as well as innovative uses of existing radiopharmaceuticals, mean that most
      nuclear medicine departments equipped with standard imaging devices can image the
      single photon imaging agents without difficulty.

PMID- 9628956
TI  - Cancer chemoprevention. A new way to treat cancer before it happens.
AB  - Cancer chemoprevention uses noncytotoxic drugs or nutrients to prevent, retard,
      or delay carcinogenesis. The future of cancer chemoprevention depends on
      understanding key cellular growth and proliferation-controlling events,
      developing markers of molecular carcinogenesis, surrogate endpoint biomarkers,
      and targeted chemopreventive approaches.

PMID- 9628957
TI  - Giving patients bad news.
AB  - Giving patients bad news involves the physician discussing the situation with the
      recipient and selected family members. Interview factors include knowledge of the
      medical facts and awareness of the patient and family dynamics. These can be
      altered as medical information is gained during the course of the illness, as
      well as a better understanding of the patient and the socio-cultural
      expectations. Despite the inevitability of death, no satisfactory uniform
      approach has been developed, because the interaction must be modulated into a
      sympathetic and humane interaction between medical provider and recipient.

PMID- 9628958
TI  - Using evidence-based medicine in clinical practice.
AB  - This article discusses the cognitive tendencies that lead to inaccurate appraisal
      of the value of tests or treatments, the role of evidence-based medicine in
      correcting them, and the need for the primary physician to provide an evidence
      based perspective. True clinical outcomes and levels of evidence are defined. The
      clinical epidemiology of testing is reviewed, with emphasis on sensitivity,
      specificity, and positive and negative predictive values. These are followed by
      criteria for usefulness in screening. Treatment evaluation is discussed in terms
      of absolute risk reduction and number needed to treat.

PMID- 9628959
TI  - Role of the primary care physician after the diagnosis of cancer. The importance
      of the team approach.
AB  - Teamwork is essential in the provision of cancer aftercare. The primary care
      physician is an important part of the aftercare team as a source of information,
      comfort and guidance to the patient.

PMID- 9628960
TI  - Management of cancer pain.
AB  - Primary care clinicians treat patients with cancer and cancer pain. It is
      essential that physicians know how to effectively manage pain including
      assessment and pharmacologic and nonpharmacologic treatment modalities. Barriers
      to adequate assessment of pain must be recognized and overcome. Pharmacologic
      regimens are based on the World Health Organization's "ladder of analgesia,"
      beginning with nonopioid medications and adding the opioid narcotics and adjuvant
      medications as necessary. Inclusion of nonpharmacologic treatments, physical and
      psychological are important for effective management.

PMID- 9628961
TI  - Considering advance directives for oncology patients.
AB  - Communication is an important cornerstone to the physician-patient relationship
      when considering advance directives. Discussing advance directives with patients
      is a process best initiated in routine, well-adult care that can be made more
      daunting when the patient is critically ill; yet, when patients are afflicted
      with cancer, communication on advance directives can be optimized when the
      primary care physician and oncologist together work with the patient. The need to
      counsel patients on advance directives regardless of the venue (whether inpatient
      or outpatient) highlights that an ongoing alliance between the oncologist and the
      primary care physician can help facilitate consent to, and allow periodic review
      of, advance directives by cancer patients. This process ensures that the
      patient's preferences are respected at life's end.

PMID- 9628962
TI  - Endometrial cancer, cervical cancer, and the adnexal mass.
AB  - Cancers of the endometrium, cervix, and ovaries account for nearly 25,000 annual
      deaths among women in the United States. In recent years, better understanding of
      the causes and risk factors associated with gynecologic malignancies has
      contributed to more effective screening and early diagnosis. Abnormal uterine
      bleeding, a palpable adnexal mass, or vague abdominal complaints in women older
      than 40 can be signs of cancer. Regular pelvic examination, combined with
      appropriate use of the Papanicolaou's smear, endometrial biopsy, transvaginal
      sonography, and other tests, is recommended.

PMID- 9628963
TI  - Male genital cancers.
AB  - Each type of male genital cancer has features that are unique in diagnosis and
      treatment. The incidences of these cancers are related to age, race, and
      environment. Early diagnosis and treatment are documented as important for all
      male genital cancers except prostate cancer, where this remains a subject of
      controversy.

PMID- 9628964
TI  - AIDS-Related malignancies.
AB  - Neoplasms are a common complication of HIV-infected individuals. The increased
      survival rates of those with HIV infection may allow the emergence of an
      increased number of cancers. The new therapeutic regimens may slow the rate of
      progression by partially restoring the integrity of the immune system.

PMID- 9628966
TI  - Cancer and depression.
AB  - There is strong evidence that depression can have profound negative effects on
      the functional status, psychologic outlook, and possibly the medical outcome of
      cancer patients. Its presence often is taken for granted by both patients and
      physicians as being either inevitable or easily explained by the grim prognosis
      and complex treatment regimens experienced by many cancer patients, and thereby
      less deserving of an aggressive approach to diagnosis and treatment. This view is
      inappropriate, and hinders an effective approach to the problem. Effective
      treatment, similar to that provided for any other depressed patient, can enhance
      the cancer patient's overall approach to life and the disease, irrespective of
      the eventual medical outcome.

PMID- 9628965
TI  - Triage of the abnormal Papanicolaou smear in pregnancy.
AB  - Triage of the abnormal Papanicolaou smear in pregnancy requires colposcopic
      evaluation and directed biopsy. If histologic cervical intraepithelial neoplasia
      is confirmed, the patient can be managed with observations and can be re
      evaluated in the postpartum period. If evidence of microinvasion is present,
      conization must be performed. For patients with invasive disease, a delay in
      therapy until fetal maturity is achieved does not compromise survival.

PMID- 9628968
TI  - [The "break" in Aristotle's presentation of genetic contributions of man and
      woman. Or: must he, who says a, always say b?].

PMID- 9628967
TI  - Physical activity and the primary prevention of cancer.
AB  - Evidence has been accumulating that suggests that physical activity may help
      reduce the risk of cancer. Physically active people have been shown to have a
      decreased rate of all-cancer mortality. The incidence of colon, breast, and
      perhaps prostate cancer are decreased in more active people when compared with
      their sedentary peers. Chronic physical activity may decrease tumor risk by its
      effect on natural immunity, antioxidant defenses, improved energy balance,
      hormonal changes, or by other unknown mechanisms.

PMID- 9628969
TI  - [Melanchthon's oration "De Hippocrate"].

PMID- 9628970
TI  - [Typhus and typhus control in German from the social history viewpoint].

PMID- 9628971
TI  - [Josef Breuer's "Damon Aber": a postscript].

PMID- 9628972
TI  - [Men, pathology, and mice].

PMID- 9628973
TI  - Medullary carcinoma of the thyroid glad: diagnostic cytopathological
      characteristics.
AB  - Sixty fine needle aspiration biopsy samples of the medullary carcinoma of the
      thyroid, 49 primary and 11 recurrent/metastatic, were reexamined in order to
      determine diagnostic features and value of auxiliary techniques. In the smears,
      tumor cells were present either as single cells or in loose cohesive groups; in
      about one third of cases, three-dimensional groups predominated. Cells were of
      different shapes round-to-oval, polyhedral and spindle. The aspirates contained
      one or all three cell types. Large mononucleated cells were present in 47/60
      cases and, in addition, in 34 of these multinucleated cells with nuclei arrayed
      in semicircular rows were present. Plasmacytoid and dendritic cells, observed in
      58/60 cases, appear to be an important diagnostic feature. Red cytoplasmic
      granules and amyloid deposits could serve as an additional diagnostic clue. Among
      the auxiliary techniques, the demonstration of calcitonin and CEA immunoreactive
      cells proved to be the most helpful.

PMID- 9628974
TI  - [Flow cytometry in prostate cancer. Evaluation of its feasibility for biopsy
      specimens and correlation with grading].
AB  - BACKGROUND: Pathologic staging and grading are the most important prognostic
      factors in prostatic cancer. Unfortunately, pathologic staging needs to be
      evaluated by surgical procedures; moreover, the proposed grading systems are
      largely based upon subjective histopathologic evaluations. In recent years, these
      problems have been approached with flow cytometry (FCM). The present study
      evaluates the significance of DNA ploidy of prostatic carcinoma assessed by FCM.
      MATERIALS AND METHODS: Microscopic slides from 132 core needle biopsies and 22
      surgical specimens of prostatic carcinoma were reviewed and classified according
      to Gleason's score modified by Epstein et al. Formalin-fixed, paraffin-embedded
      tissue samples were prepared for FCM evaluation using standard techniques.
      Adequate histograms were obtained from 113 biopsies (85.6%) and from all the
      surgical specimens (100%). RESULTS: Among the 113 biopsy specimens, a
      statistically significant correlation was found between DNA ploidy and Epstein's
      grading, since high-grade neoplasms accounted for 40.38% of non-diploid cases and
      only for 21.33% of diploid cases (chi square = 5.8; p = 0.05). Moreover,
      tetraploid tumors were defined as a separate FCM category with an absolute
      prevalence (65.52%) of non-high grade neoplasms (chi square = 5.9; p = 0.05).
      Although not submitted to statistical analysis, data collected from surgical
      specimens showed similar distribution. CONCLUSIONS: DNA ploidy assessment by FCM
      is a viable procedure in the majority of needle biopsy tissue samples of
      prostatic carcinoma; it may produce prognostic parameters with greater
      objectivity than conventional histologic grading.

PMID- 9628975
TI  - [Kikuchi's disease and proteinaceous lymphoadenopathy in 4 patients with HIV
      infection].
AB  - In the lymphadenopathy occurring in the acquired immunodeficiency syndrome (AIDS)
      and the AIDS related complex (ARC), consistent histologic patterns have been
      described with some variants thereof, such as angioimmunoblastic lymphadenopathy
      like or Castleman disease-like. In four such patients we have observed two other
      types of nodal lesions. Three patients had lymph node biopsies showing the
      characteristic histologic and immunophenotypic features of histiocytic
      necrotizing lymphadenitis (Kikuchi's disease). These were two males, 26 and 35
      year old, with bilateral axillary and cervical lymphadenopathy, respectively, and
      one female, 29-years old with peripheral and abdominal lymphadenopathy. One
      patient had proteinaceous lymphadenopathy. This was a 26-year old man with
      disseminated lymphadenopathy and a small monoclonal IgG/k peak in the serum.
      Whether these two processes are direct effects of the HIV virus on the immune
      system or due to intercurrent etiologic factors, has to be determined. These
      observations, however, indicate that the range of nodal lesions (that the
      pathologist may encounter) in AIDS/ARC is wider than previously reported.

PMID- 9628976
TI  - [Use of hydrogen peroxide to neutralize formalin vapors during tissue sampling].
AB  - The problem of formaldehyde exhalation during tissue sampling for histological
      examinations is deeply felt in each histological laboratory. Most of adoptable
      methods which are used for the safeguard of operators' health can't frequently
      avoid situations where formaldehyde rate in the air exceeds safety limits. This
      has led us to the search of an easy and quick method to neutralize this vapour
      during the tissue sampling. We have pursued our aim using hydrogen peroxide
      which, in force of its oxidizing action, transforms formaldehyde into carbonic
      anhydride and water, which are two innocuous products.

PMID- 9628977
TI  - Nerve biopsy in patients with AIDS.
AB  - Patients with AIDS can present clinical involvement of the peripheral nervous
      system due to different causes. In the present work, it was studied the
      histopathological changes in sural nerve biopsy of fifteen patients with AIDS
      with this clinical involvement. It was observed the presence of a polyarteritis
      nodosa-like vasculitis of small arteries with fibrinoid necrosis in the sural
      nerve of 3 patients, one of them associated to polyradiculitis due to
      cytomegalovirus infection (CMV). Six patients presented mild axonal loss by light
      microscopy. Three other patients had a more important axonal neuropathy with
      myelin ovoids by teasing. By the electron microscopy in these patients were
      observed some fibers with axonal damage. The other three patients had normal
      sural nerves. We concluded that sural nerve biopsy may be important in peripheral
      neuropathies or myelo-radiculo-polyneuropathies in AIDS especially to search for
      nerve vasculitis, because it can change the therapeutic approach.

PMID- 9628978
TI  - [Case report of a double ano-rectal neoplasia (adenocarcinoma and melanoma)].
AB  - The association in a single organ of two neoplasms with different, histogenensis
      is uncommon. A dual ano-rectal neoplasms, pigmented malignant melanoma in
      collision with adenocarcinoma is reported, along with a discussion concerning the
      problems related with primary origin of the melanocytic component.

PMID- 9628979
TI  - [Neural infiltration in benign gallbladder lesions. Description of a case].
AB  - Neural infiltration is considered a very useful marker of malignancy in the
      biliary tract. Aim of this study is to report a case of benign epithelium of the
      gallbladder with neural infiltration and to review the literature.

PMID- 9628980
TI  - [Multiple Fordyce-type angiokeratomas of the scrotum. An iatrogenic case].
AB  - BACKGROUND: Angiokeratoma is a wart-like vascular lesion of the skin. There are
      five types of angiokeratoma: the Mibelli-type, the Fordyce-type, the solitary and
      multiple (papular) types, the angiokeratoma circumscriptum, and the angiokeratoma
      corporis diffusum. The "Mibelli-type" occurs on the acral sites, mainly digits,
      of young people affected by repeated attacks of chilblain, which result in a
      deleterious effects on vessel walls. The "Fordyce-type" occurs on the scrotal
      skin of young and adults as a secondary effect to an increased blood pressure in
      scrotal veins. An equivalent form affecting adult females and occurring
      analogously on the skin of the vulva is also on record. The "solitary and
      multiple papular types" of young individuals affect the lower extremities and is
      considered a consequence of a congenital deficiency of elastic tissue in regional
      veins. We suggest the term "acquired angiokeratomas" for these three above
      mentioned clinical forms of angiokeratomas, leaving apart the other two types
      which are essentially congenital. In fact the "angiokeratoma circumscriptum" is a
      nevoid hamartomatous lesion arising early in life during infancy or childhood,
      sometimes in association with other congenital malformation of other sites, while
      the "angiokeratoma corporis diffusum" almost always occurs in association with
      enzyme disorders, usually alpha-galactosidase A enzyme deficiency (Anderson-Fabry
      disease), an X-linked recessive disorder affecting homozigous male patients in
      their adulthood. CASE REPORT: A case of multiple angiokeratomas of the scrotum
      (Fordyce-type) arisen in a 62-year old male patient following surgical amputation
      of the penis and bilateral inguino-crural lymphadenectomy for carcinoma of the
      penis is reported on. RESULTS AND CONCLUSION: Although they are well on record
      cases of angiokeratomas of the scrotum arising after surgical injuries to the
      outer vein pudenda (mainly following inguinocrural hernioplasty), based on a
      computerized search of the literature on theme this case represents the first
      iatrogenic example of such an occurrence. The pathogenetic mechanism leading to
      the the rise of angiokeratomas mediated by the increase of the blood pressure in
      the superficial scrotal veins is discussed. This example represents an additional
      case report of inevitable and sometimes unsuspected iatrogenic pathology in
      medicine.

PMID- 9628981
TI  - [Pulmonary neuroendocrine neoplasia: from molecular biology to the clinic, by way
      of immunohistochemistry].

PMID- 9628982
TI  - [Amyloidosis. Clinico-pathological profile. II. Diagnosis].

PMID- 9628983
TI  - [DCC changes and prognosis in colorectal carcinoma].

PMID- 9628984
TI  - [Bcl-6: a protooncogene co-involved in B-lymphocyte differentiation and in the
      pathogenesis of diffuse, large-cell non-Hodgkin's lymphomas of the B phenotype].

PMID- 9628985
TI  - [Conquerors and conquered].

PMID- 9628986
TI  - [Enigmatic pathology, a life of some mystery: Guido Banti].

PMID- 9628987
TI  - [Electronic memory and medical reports].

PMID- 9628988
TI  - Effects of token variability on our ability to distinguish between vowels.
AB  - Even when the speaker, context, and speaking style are held fixed, the physical
      properties of naturally spoken utterances of the same speech sound vary
      considerably. This variability imposes limits on our ability to distinguish
      between different speech sounds. We present a conceptual framework for relating
      the ability to distinguish between speech sounds in single-token experiments (in
      which each speech sound is represented by a single wave form) to resolution in
      multiple-token experiments. Experimental results indicate that this ability is
      substantially reduced by an increase in the number of tokens from 1 to 4, but
      that there is little further reduction when the number of tokens increases to 16.
      Furthermore, although there is little relation between the ability to distinguish
      between a given pair of tokens in the multiple- and the 1-token experiments,
      there is a modest correlation between the ability to distinguish specific vowel
      tokens in the 4- and 16-token experiments. These results suggest that while
      listeners use a multiplicity of cues to distinguish between single tokens of a
      pair of vowel sounds, so that performance is highly variable both across tokens
      and listeners, they use a smaller set when distinguishing between populations of
      naturally produced vowel tokens, so that variability is reduced. The
      effectiveness of the cues used in the latter case is limited more by internal
      noise than by the variability of the cues themselves.

PMID- 9628990
TI  - Opponent motion interactions in the perception of transparent motion.
AB  - Interactions in the perception of motion transparency were investigated using a
      signal-detection paradigm. The stimuli were the linear sum of two independent,
      moving, random-check "signal" textures and a third texture consisting of dynamic
      random "noise." Performance was measured as the ratio of squared signal and noise
      contrasts was varied (S2/N2). Motion detectability was poorest when the two
      signal textures moved in opposite directions (180 degrees), intermediate when
      they moved in the same direction (0 degrees), and best when the textures moved in
      directions separated by 90 degrees in the stimulus plane. This pattern of results
      held across substantial variations in velocity, field size, duration, and texture
      element size. Motion identification was also impaired, relative to 0 degrees, in
      the 180 degrees but not in the 90 degrees condition. These results are consistent
      with the idea that performance in the opponent-motion condition is limited by
      inhibitory (or suppressive) interactions. These interactions, however, appear to
      be direction specific: little, if any, inhibition was observed for perpendicular
      motion.

PMID- 9628989
TI  - Cross-modal links in exogenous covert spatial orienting between touch, audition,
      and vision.
AB  - Three experiments investigated cross-modal links between touch, audition, and
      vision in the control of covert exogenous orienting. In the first two
      experiments, participants made speeded discrimination responses (continuous vs.
      pulsed) for tactile targets presented randomly to the index finger of either
      hand. Targets were preceded at a variable stimulus onset asynchrony (150, 200, or
      300 msec) by a spatially uninformative cue that was either auditory (Experiment
      1) or visual (Experiment 2) on the same or opposite side as the tactile target.
      Tactile discriminations were more rapid and accurate when cue and target occurred
      on the same side, revealing cross-modal covert orienting. In Experiment 3,
      spatially uninformative tactile cues were presented prior to randomly
      intermingled auditory and visual targets requiring an elevation discrimination
      response (up vs. down). Responses were significantly faster for targets in both
      modalities when presented ipsilateral to the tactile cue. These findings
      demonstrate that the peripheral presentation of spatially uninformative auditory
      and visual cues produces cross-modal orienting that affects touch, and that
      tactile cues can also produce cross-modal covert orienting that affects audition
      and vision.

PMID- 9628991
TI  - Overestimation of base-rate differences in complex perceptual categories.
AB  - The optimality of multidimensional perceptual categorization performance was
      examined for several base-rate ratios, for both integral and separable dimension
      stimuli, and for complex category structures. In all cases, the optimal decision
      bound was highly nonlinear. Observers completed several experimental sessions,
      and all analyses were performed at the single-observer level using a series of
      nested models derived from decision-bound theory (Maddox, 1995; Maddox & Ashby,
      1993). In every condition, all observers were found to be sensitive to the base
      rate manipulations, but the majority of observers appeared to overestimate the
      base-rate difference. These findings converge with those for cases in which the
      optimal decision bound was linear (Maddox, 1995) and suggest that base-rates are
      learned in a similar fashion regardless of the complexity of the optimal decision
      bound. Possible explanations for the consistent overestimate of the base-rate
      difference are discussed. Several continuous-valued analogues of Kruschke's
      (1996) theory of base-rate learning with discrete-valued stimuli were tested.
      These models found some support, but in all cases were outperformed by a version
      of decision-bound theory that assumed accurate knowledge of the category
      structure and an overestimate of the base-rate difference.

PMID- 9628992
TI  - Sudden changes in spectrum of an echo cause a breakdown of the precedence effect.
AB  - The effect of changing the frequency components of an echo relative to the sound
      source was examined in a two-choice discrimination task. Subjects sat in an
      anechoic chamber and discriminated the direction of the lag noise burst within a
      lead-lag pair presented over loudspeakers. The leading noise burst was broadband,
      and the lagging burst was either high- or low-pass filtered. On some conditions,
      this test burst pair was preceded by a conditioning train of burst pairs, which
      also had a broadband lead and either a high- or low-frequency lag. When the
      frequency content of the echo was held constant across the conditioning train and
      test burst pair, echo suppression that was built up during the repeating train
      was maintained for the test burst pair, shown by the subjects' poor performance
      in detecting the location of the lagging burst. By comparison, subjects had
      little difficulty in localizing the lagging burst when the frequency content of
      the echo changed between the conditioning train and the test burst, indicating
      that any buildup of suppression during the train was broken when the lagging
      burst's spectrum shifted. The data are consistent with an interpretation in which
      echo suppression is temporarily broken when listeners' built-up expectations
      about room acoustics are violated.

PMID- 9628993
TI  - General contrast effects in speech perception: effect of preceding liquid on stop
      consonant identification.
AB  - When members of a series of synthesized stop consonants varying acoustically in
      F3 characteristics and varying perceptually from /da/ to /ga/ are preceded by
      /al/, subjects report hearing more /ga/ syllables relative to when each member is
      preceded by /ar/ (Mann, 1980). It has been suggested that this result
      demonstrates the existence of a mechanism that compensates for coarticulation via
      tacit knowledge of articulatory dynamics and constraints, or through perceptual
      recovery of vocal-tract dynamics. The present study was designed to assess the
      degree to which these perceptual effects are specific to qualities of human
      articulatory sources. In three experiments, series of consonant-vowel (CV)
      stimuli varying in F3-onset frequency (/da/-/ga/) were preceded by speech
      versions or nonspeech analogues of /al/ and /ar/. The effect of liquid identity
      on stop consonant labeling remained when the preceding VC was produced by a
      female speaker and the CV syllable was modeled after a male speaker's
      productions. Labeling boundaries also shifted when the CV was preceded by a sine
      wave glide modeled after F3 characteristics of /al/ and /ar/. Identifications
      shifted even when the preceding sine wave was of constant frequency equal to the
      offset frequency of F3 from a natural production. These results suggest an
      explanation in terms of general auditory processes as opposed to recovery of or
      knowledge of specific articulatory dynamics.

PMID- 9628995
TI  - The dispersions of estimates of sensitivity obtained from four psychophysical
      procedures: implications for experimental design.
AB  - The dispersions of estimates of sensitivity obtained from the yes-no, two
      alternative forced-choice (2AFC), matching-to-sample, and same-different tasks
      were examined to determine which task would be more appropriate to use in a given
      experimental context. Consideration was given to the effects of corrections for
      extreme sampled proportions. These corrections result in biased estimators, and
      hence the mean-square deviation of the sampled values about the population mean
      [MSD(d')], rather than that about the mean of the estimates [VAR(d')], indicates
      more completely the extent of the error in the estimator. For barely
      discriminable events (d' approximately equal to 0.5), the yes-no and 2AFC tasks
      had the lowest values of MSD(d'). However, for very discriminable events(d > 3),
      the same-different and matching-to-sample tasks had lower values of MSD(d').

PMID- 9628994
TI  - Response time distributions in multidimensional perceptual categorization.
AB  - Three speeded categorization experiments were conducted using separable dimension
      stimuli. The form of the category boundary was manipulated across experiments,
      and the distance from category exemplars to the category boundary was manipulated
      within each experiment. Observers completed several sessions in each experiment,
      yielding 300-400 repetitions of each stimulus. The large sample sizes permitted
      accurate estimates of the response time (RT) distributions and RT hazard
      functions. Analyses of these data indicated: (1) RT was faster for stimuli
      farther from the category boundary, and this stochastic dominance held at the
      level of the RT distributions; (2) RT was invariant for all stimuli the same
      distance from the category boundary; (3) when task difficulty was high, errors
      were slower than correct responses, whereas this difference disappeared when
      difficulty was low; (4) small, consistent response biases appeared to have a
      large effect on the relation between correct and error RT; (5) the shape of the
      RT hazard function was qualitatively affected by distance to the category
      boundary. These data establish a rich set of empirical constraints for testing
      developing models of categorization RT.

PMID- 9628996
TI  - The influence of chemical complexity on the perception of multicomponent odor
      mixtures.
AB  - The present study investigates the hypothesis that complex object odors (odors
      that emanate from flowers, foods, sewage, etc.) that consist of dozens of
      odorants are processed and encoded as discrete entities, as if each was a single
      chemical odor. To test this hypothesis, the capacity of trained subjects to
      discriminate and identify the components of stimuli consisting of one to eight
      object odors was determined. The results indicated that subjects could only
      identify up to four object odors in a mixture, which is similar to earlier
      findings with mixtures that contained only single chemical odors. The limited
      capacity was also reflected in the number of odors selected, regardless of
      whether the choices were correct or incorrect, in confidence ratings, and in
      decision times. The identification of a limited number of object odors in every
      mixture that was presented suggests that both associative (synthetic) and
      dissociative (analytic) processes are involved in the perceptual analysis of odor
      mixtures.

PMID- 9628997
TI  - Prehension movements and perceived object depth structure.
AB  - This study asked the question, "Will the motor pattern to a perceived two
      dimensional (2-D) object differ from that same object when it is perceived as
      three dimensional (3-D)?" Subjects were required to reach and grasp an apple that
      could appear to be 2-D or 3-D. Two experimental sessions were conducted. In
      Condition A, the apple was initially perceived to be 2-D, but, for 20% of trials,
      it suddenly shifted to a 3-D apple at movement onset. In Condition B, the apple
      was initially perceived to be 3-D, but, for 20% of trials, it suddenly shifted to
      a 2-D silhouette of the same apple. For control trials, subjects grasped the
      perceived 2-D apple as if it were a disc (82%), and they grasped the 3-D apple,
      as they would a normal apple, with a whole-hand grasp (86%). For Condition A
      perturbed trials, there was a rapid change from a 2-D precision grip to a 3-D
      whole-hand prehension, whereas the converse was true for the opposite
      perturbation. Peak acceleration was anticipated for Condition A perturbed trials
      but not for Condition B perturbed trials. These results indicate that the motor
      patterns we use in interacting with an object are strongly influenced by the way
      we perceive the object in real time, and that object affordances, such as
      dimension, can override the influence exerted by existing representations.

PMID- 9628998
TI  - Relative size perception at a distance is best at eye level.
AB  - Relative size judgments were collected for two objects at 30.5 m and 23.8 from
      the observer in order to assess how performance depends on the relationship
      between the size of the objects and the eye level of the observer. In three
      experiments in an indoor hallway and in one experiment outdoors, accuracy was
      higher for objects in the neighborhood of eye level. We consider these results in
      the light of two hypotheses. One proposes that observers localize the horizon as
      a reference for judging relative size, and the other proposes that observers
      perceive the general neighborhood of the horizon and then employ a height-in
      visual-field heuristic. The finding that relative size judgments are best around
      the horizon implies that information that is independent of distance perception
      is used in perceiving size.

PMID- 9628999
TI  - Localizing the first position of a moving stimulus: the Frohlich effect and an
      attention-shifting explanation.
AB  - When subjects are asked to determine where a fast-moving stimulus enters a
      window, they typically do not localize the stimulus at the edge, but at some
      later position within that window (Frohlich effect). We report five experiments
      that explored this illusion. An attentional account is tested, assuming that the
      entrance of the stimulus in the window initiates a focus shift toward it. While
      this shift is under way, the stimulus moves into the window. Because the first
      phenomenal (i.e., explicitly reportable) representation of the stimulus will not
      be available before the end of the focus shift, the stimulus is perceived at some
      later position. In Experiment 1, we established the Frohlich effect and showed
      that it size depends on stimulus parameters such as movement speed and movement
      direction. In Experiments 2 and 3, we examined the influence of eye movements and
      tested whether the effect changed when the stimuli were presented within a
      structural background or when they started from different eccentricities. In
      Experiments 4 and 5, specific predictions from the attentional model were tested:
      In Experiment 4 we showed that the processing of the moving stimulus benefits
      from a preceding peripheral cue indicating the starting position of the
      subsequent movement, which induces a preliminary focus shift to the position
      where the moving stimulus would appear. As a consequence the Frohlich effect was
      reduced. Using a detection task in Experiment 5, we showed that feature
      information about the moving stimulus is lost when it falls into the critical
      interval of the attention shift. In conclusion, the present attentional account
      shows that selection mechanisms are not exclusively space based; rather, they can
      establish a spatial representation that is also used for perceptual judgement-
      that is, selection mechanisms can be space establishing as well.

PMID- 9629000
TI  - What is learned about nontarget items in simple visual search?
AB  - Human sensitivity to correlational structure between nontargets and likelihood of
      target presence in a visual letter-search task were studied in two experiments.
      In each of these experiments, the performance of subjects for whom the nontarget
      information was altered in the final trial block was compared with the
      performance of subjects for whom the nontarget information did not change. When
      stimulus strings were presented individually on a computer screen and subjects
      were required to make a yes-no decision about target presence (Experiment 1), the
      change in nontarget structure resulted in increased reaction times for target
      absent trials. When subjects searched simultaneously for three possible targets
      (Experiment 2), the change in nontarget structure produced increased error rates
      and increased reaction times for both target-absent and target-present trials.
      Correlations between the amount of predictive information in individual stimulus
      strings and reaction times also showed that both switching and nonswitching
      subjects were sensitive to the nontarget context. However, neither self-reports
      of strategy nor postexperiment choices between context-consistent and
      inconsistent letter strings indicated any explicit knowledge of the predictive
      information in the nontarget stimuli. Subjects can thus acquire and benefit from,
      apparently without awareness, information about subtle correlational structure in
      nontarget elements in simple visual search.

PMID- 9629001
TI  - Size perception by vision and kinesthesia.
AB  - When two sizes, one perceived by vision and the other by kinesthesia, are
      apparently equal, the physical relationship between them varies: The sizes may be
      equal, or the visual size may be larger than the kinesthetic size, or vice versa.
      In this study, the method of cross-modal matching and the method of magnitude
      production were used to explore the relationship between apparently equal sizes
      (5-40 cm) perceived by vision and by kinesthesia. The sizes were linear or
      circular, and the mode of standard presentation was visual, kinesthetic, or
      verbal. The size and the direction of the intermodal mismatch varied with the
      size of the standard. It was also found that an apparent length of movement
      varied with the direction of movement. In all conditions, the relationship
      between apparently equal visual and kinesthetic sizes was well approximated by a
      power function.

PMID- 9629002
TI  - [Problems of public health reform in the Russian Federation].

PMID- 9629003
TI  - [Medical ethics, deontology and bioethics].

PMID- 9629004
TI  - [Physical development of children under conditions of formation of a new social
      structure of the population].

PMID- 9629005
TI  - [Social and hygienic conditions of family creation and birth of the first child].
AB  - Discusses the problems of public health reformation using the so-called new
      social contract, put forward in Russia by J. Rice, heading the ZdravReform
      program. Based on analysis of the socio-hygienic conditions of family creation
      and birth of the first child, the authors propose the following assumption:
      creation of a family and appearance of the first child is one factor occupying a
      special place within the framework of the new social contract and validate this
      assumption by the data of their sociomedical research.

PMID- 9629006
TI  - [Therapeutic and prophylactic care of disabled children under conditions of a
      pediatric outpatient clinic].
AB  - The volume and type of treatment and prophylactic care rendered on an outpatient
      basis to children during a year is assessed based on a sampling from files of
      2083 disabled children living in a large industrial city Ufa. In contrast to the
      entire population of children, each disabled child receives more visits from
      doctors at home and visits the health center more often. The majority of visits
      to the health center are for treatment and diagnosis and for consultations. Local
      doctors are visited mainly for prevention. The activity of local nurses
      responsible for follow-up of disabled children is low.

PMID- 9629007
TI  - [Evaluation of the dynamics of mortality over short time intervals].
AB  - Discusses the problem of assessing the time course of demographic values for
      short periods of time under conditions when stable long-term tendencies are
      absent. The author proposes to solve this problem by an extra analysis of
      alternative demographic models, e.g. Brass model. The method is illustrated by
      data for the Saratov district.

PMID- 9629008
TI  - [Population health and activities of a territorial fund of obligatory medical
      insurance].
AB  - The increasing relationship between the social status and disease incidence in
      the population of the Voronezh district makes it necessary that the territorial
      funds of obligatory medical insurance be rendered the role of the subject of the
      interdiscipline system of health protection, and the main trends in its activity
      are outlined.

PMID- 9629009
TI  - [Role of federal purposeful public health programs in the realization of the
      state research and technological policy].
AB  - Purposeful scientific and technological programs are an important component in
      organization and management of the research process. At present such programs are
      in the crisis, which prevents implementation of their normal function: scientific
      and technological progress in public health. Approaches to purposeful programs
      are to be altered, new effective means for realization of the state scientific
      and technologic policy searched for, and a novel economic mechanism stimulating
      the application of research findings created.

PMID- 9629010
TI  - [Essential measures of an organizational-medical character aimed atdecreasing the
      incidence of diseases of the circulatory system and mortality caused by them in
      modern Russia].
AB  - Mortality caused by diseases of the circulatory system is analyzed on the basis
      of files of the Ministry of Health and of the State Statistical Committee of
      Russia and the results are correlated to the objective parameters reflecting the
      potentialities of cardiological service in Russia and the actual status of
      prophylaxis, including regular check-ups. Conclusions are drawn and
      recommendations offered.

PMID- 9629011
TI  - [Current problems of the quality of medical care rendered in the outpatient
      clinic and approaches to their solution].

PMID- 9629012
TI  - [Essence and main features of marketing in the market place of services and goods
      of the medical-manufacturing complex].
AB  - The essence and specific features of marketing are disclosed, based on the
      results of studies of the drug market. The market of outpatient and hospital
      services is analyzed using the marketing means. The succession of compartments of
      the marketing programs applied is presented.

PMID- 9629013
TI  - [Conceptual and terminologic aspects of licensing-accreditation activity in
      public health].

PMID- 9629014
TI  - [History of the introduction of clinical training in the Medical Faculty of the
      Moscow University in the first half of the XIX century].

PMID- 9629015
TI  - [Russian medics in France in the XIX century].

PMID- 9629016
TI  - [Professor H. Zeiss (1888-1949) and the history of medicine in Russia (70th
      anniversary of one publication)].

PMID- 9629017
TI  - [Memorable dates and anniversaries in the history of medicine and public health
      in 1998].

PMID- 9629018
TI  - Appointment of medical officers of health (food safety) is essential for
      achieving food safety objectives in the UK. Response to food borne illness
      section (4.44-4.49) of the White Paper, the Food Standard Agency--a force for
      change, MAFF January 1998.
AB  - National surveys reveal that the public has lost confidence in the safety of
      food. There is lack of co-ordination and failure to overcome institutional
      barriers at many levels throughout the food chain. The abolition of the post of
      medical officer of health and the public health departments of local government
      over which it presided, in view of many, including members of parliament, has
      been the most damaging of all changes to the public health and many have asked
      for the restoration of this post. Health departments have no overall statutory
      responsibility for food safety. The medical expertise of medical officers of
      health provided the executive authority with the necessary support in managing
      and controlling outbreaks of food poisoning, a point emphasised in the
      recommendations made by an inquiry set up by the government following the worst
      ever outbreak of food poisoning in Lanarkshire, Scotland, UK. Only such an
      appointment at local level will restore public confidence in food safety.

PMID- 9629019
TI  - Hearing impairment among young Chinese in an urban area.
AB  - To evaluate hearing levels among young Chinese in an urban area, audiometry was
      carried out in Jinan city, Shandong Province, China. The subjects were 442
      healthy school children and students ranging in age from 6-19 y. All subjects
      were asked to complete a brief questionnaire on otological symptoms, personal
      histories and use of noisy playthings. Audiometric threshold testing was
      performed at the audiometric frequencies of 0.5, 1, 2, 4 and 8 kHz. Logistic
      regression analysis was used to analyse the items of personal histories related
      to hearing impairment. Forty-five subjects (10% of the subjects) were classified
      as abnormal. Nineteen ears of the abnormal subjects showed 4 kHz-dip and 38 ears
      showed high-frequency hearing impairment. Lower prevalence of hearing impairment
      was found when compared with young Chinese in a rural area (20%). The logistic
      regression analysis showed that head trauma may be the cause of hearing
      impairment among young Chinese in urban areas. Otological examinations for all
      children sustaining head trauma are recommended.

PMID- 9629020
TI  - Feasibility of community-based hearing screening using transient evoked
      otoacoustic emissions.
AB  - This study investigated the feasibility of obtaining transient evoked otoacoustic
      emissions for hearing screening purposes from infants and children at seven child
      health clinics. Factors affecting the outcomes of the community hearing screening
      program were examined. The subject group comprised 2305 children aged two weeks
      to 11 y 11 mon. Many children were attending the clinics for initial immunisation
      at two months of age. While there were no exclusion criteria for the 1305 young
      infants tested who were in this category, all other children were screened only
      upon receipt of a referral from clinic nurses. Results indicated that 182
      children (7.9%) did not complete the screening for both ears within the time
      constraint (usually 15 min) of a child health clinic visit. Three hundred and
      sixty-two children (15.7%) failed the first screening. Of the 226 children who
      returned for a second screening test, separated from the first by at least two
      weeks, 121 children failed. With parents' consent, 107 children (4.6% of all
      participants) were referred for diagnostic or medical assessment. Subsequently,
      77 out of 94 children who received audiological or medical assessment were found
      to have some degree of hearing impairment. The majority of positive screening
      results were associated with middle ear disorder. The results suggest that TEOAE
      screening has potential as a technique in the community health setting but
      improvements in instrumentation are required to reduce 'could not test' cases and
      to separate probable conductive hearing loss from cases likely to have other
      disorders.

PMID- 9629021
TI  - Reasons for non-compliance with screening for infection with Helicobacter pylori,
      in a multi-ethnic community in Leicester, UK.
AB  - In this study, we aimed to identify reasons for non-compliance with a screening
      programme for Helicobacter pylori (H pylori), in a multi-ethnic community and to
      assess the effectiveness of Asian language materials towards increasing
      compliance. A serological screening test for infection with H pylori was offered
      to 200 Asians and 200 non-Asians (mainly Europeans), aged 21-55 y, registered at
      a single general practice. Reasons for non-attendance for screening were
      identified by reply slip or interview. A second group of 200 Asians who were
      offered screening were sent information in Gujarati as well as English. When
      information was mailed in English only, 30% Asians and 22% non-Asians attended (P
      = 0.09, ns). Stated reasons for non-attendance in the Asian group were not
      generally language related; reasons were similar in the Asian and non-Asian
      groups and were most frequently related to other commitments. The use of
      materials in Gujarati did not improve compliance. Language problems should not be
      assumed to dominate reasons for non-compliance with screening in ethnic minority
      groups. In common with those of UK origin, subjects from ethnic minority groups
      may more generally have insufficient interest in preventive medicine for them to
      prioritise health screening above other commitments.

PMID- 9629022
TI  - Are women who have abortions different from those who do not? A secondary
      analysis of the 1990 national survey of sexual attitudes and lifestyles.
AB  - Studies of women undergoing termination of a pregnancy are often used to make
      recommendations about family planning and health education policy. However, it is
      not clear how similar the women in these studies are to the general population of
      women of childbearing age. Our secondary analysis of the National Sexual
      Attitudes and Lifestyles Survey allowed us to test the hypothesis that women who
      have undergone an abortion are the same as those who have not (in terms of socio
      demographic characteristics, lifestyles, and attitudes). Our findings show
      significant differences between these two groups of women, particularly regarding
      ethnicity, marital status, number of natural children, lifetime number of sexual
      partners, and attitudes to abortion. We conclude that family
      planning/reproductive health services and health education policies need to take
      these differences into account and that further research is required to explain
      why these differences arise.

PMID- 9629023
TI  - Tuberculosis mortality in notified cases from 1989-1995 in Birmingham.
AB  - This is a retrospective descriptive study examining medical records of notified
      cases of tuberculosis in Birmingham, UK, who died before completion of treatment,
      plus notified cases identified at postmortem. During the study period, 1989-1995,
      there were a total of 2088 notifications of tuberculosis of which 75 (3.6%) died.
      This case-fatality rate is lower than that reported from earlier studies, a
      finding which may be due to improved ascertainment, earlier diagnosis and
      improved treatment in recent years. Forty-five deaths (60%) were in males and 30
      (40%) in females. The median age at death was 66 y. Forty-five deaths (60%) were
      among the white ethnic group, 21 (28%) among persons of Indian sub-continent
      origin, 4 (5.3%) among Black Caribbeans and 5 (6.6%) among the other ethnic
      groups. Case-fatality rates were significantly higher (P < 0.01) in caucasians
      (9.4%) than in Asians (1.5%) and only half of this difference was explained by
      the age of those affected. Twenty-two (29%) cases were confirmed by a positive
      sputum smear and a further 23 (31%) by a positive sputum culture. Eighteen (24%)
      cases also had histological confirmation. Twelve (16%) cases were identified on
      autopsy. The case fatality rate in respiratory disease was significantly higher
      (RR = 1.19, P > 0.05) than in non-respiratory disease. As delay in diagnosis is
      likely to be the main contributing factor leading to death, a high index of
      suspicion of tuberculosis is needed when investigating elderly patients with
      general chronic illness, especially if there are prolonged respiratory symptoms.
      Early diagnosis will reduce mortality as the disease rapidly responds to
      treatment.

PMID- 9629024
TI  - The mental and physical health of miners following the 1992 national pit closure
      programme: a cross sectional survey using General Health Questionnaire GHQ-12 and
      Short Form SF-36.
AB  - BACKGROUND: In the twelve months following the announcement of the UK pit closure
      programme in October 1992, 22,500 miners were made redundant. In 1994 we
      undertook a cross-sectional survey to determine whether the mental and physical
      health of men who had been employed in the Nottinghamshire mining industry
      differed from that of the general population. METHODS: A postal questionnaire was
      designed incorporating the General Health Questionnaire (GHQ-12), and six domains
      from SF-36. Questionnaires were sent to 1064 miners and ex-miners and 2097 other
      men in Nottinghamshire. Non-responders were sent two reminders. RESULTS: The
      final response rate was 51%. The percentage of responders with GHQ-12 scores of
      three or more (suggesting psychological disorder) was 46% for those still
      employed in the mining industry, 52% for unemployed former miners and 22% for
      working non-miners (odds ratios: 3.0 [95% C.I. 2.2-4.1] for current miners and
      3.9 [95% C.I. 2.6-5.7] for unemployed miners compared with working non-miners).
      The miners and ex-miners also had lower scores (suggesting greater morbidity) for
      each of the SF-36 domains tested. When stratifying for age in respondents of
      social classes IIIM-V the scores of current miners were significantly lower than
      those of working non-miners (P < 0.01). CONCLUSIONS: This study suggests that
      when surveyed in 1994, men who had been employed in three Nottinghamshire
      collieries in 1992 were psychologically and physically disadvantaged compared
      with working non-miners. Whether these findings are a result of pit closures is
      uncertain. However, significant potential health needs have been demonstrated.

PMID- 9629025
TI  - Health needs assessment in primary care: the evolution of a practical public
      health approach.
AB  - The purpose of the paper is to place health needs assessment in its primary care
      context. This is a dynamic context where changes in policies, staff roles and
      patient expectations have all to be considered. Given this complexity and the
      variations between practices, it is necessary to help primary health care teams
      (PHCTs) to understand their stage of development and how this will directly
      affect any health needs assessment. The technical and methodological aspects of
      health needs assessment have been explored and described by others, and that work
      will not be duplicated here. This paper reviews the health needs assessment (HNA)
      work of the Ribblesdale Total Purchasing Project (RTPP) and then sets this review
      against the political, organisational, professional and practical pressures that
      currently confront primary care. Out of this analysis emerges a diagnostic and
      development tool which links together, and emphasises the intimate relationships
      between, five stages of development needed for effective primary care-oriented
      health needs assessment work. The emphasis is on understanding the place of
      health needs assessment within the general processes and systems of the primary
      health care team. The paper concludes by suggesting ways in which public health
      practitioners and specialists might approach the task of supporting and
      influencing the evolution of the recently proposed Primary Care Groups and
      Primary Care Trusts. The overall intention of the article is to stimulate debate
      and action.

PMID- 9629026
TI  - Alcohol-related mortality in Italy.
AB  - This study evaluated the impact of alcohol drinking habits on mortality in Italy
      during the 1980-1990 period. Alcohol Attributable Fractions for a list of Alcohol
      Related Diseases were assessed from national and international medical literature
      and then applied to national mortality data according to 5 y age groups, sex, and
      place of residence for each year of the 1980-1990 period. Mortality rates and 95%
      Confidence Intervals were standardized with the direct method. Years of potential
      life lost (YPLL) were calculated for 1990. 18,033 Italian residents died during
      1990 from causes related to alcohol drinking, representing 3.3% of general
      mortality (males 4.6%; females 2.0%) which corresponded to over 200,000 YPLL up
      to age 70 y. Chronic diseases account for 65% of alcohol-related mortality. Age
      adjusted death rates declined in both genders during 1980-1990. Geographic
      differences in death rates are well evident. Alcohol drinking is a strong
      determinant of mortality in Italy. The variability of alcohol-related death rates
      across the country and the comparison with the results from other populations
      suggest that health consequences, mainly liver damage, of alcohol intake in Italy
      may be affected by other factors than alcohol itself. The need for further
      methodological efforts to improve alcohol attributable fraction estimates is
      recommended.

PMID- 9629027
TI  - Predisposition to acute respiratory infections among overweight preadolescent
      children: an epidemiologic study in Poland.
AB  - This cross-sectional field health survey has as its subjects 1129 preadolescent
      children resident in Krakow. Trained health visitors interviewed the mothers at
      the children's schools or at the parents' homes in order to gather standardized
      information regarding the families' social background and the families' and
      children's respiratory health and episodes of respiratory infections.
      Predisposition to respiratory infections in children has been defined as frequent
      spells (3 or more) of acute respiratory infections experienced by a given child
      over the 12 months preceding the interview. Clinical examination of children
      consisted of anthropometric measurements and spirometric testing. Anthropometric
      measurements (weight and height) were used for calculation of the body mass index
      (kg/m2). A child whose BMI was 20 or higher was defined as overweight (90th
      percentile). Susceptibility to acute respiratory infections was related
      significantly to body mass index. The children with BMI > or = 20 experienced
      twice as high a risk for acute respiratory infections than children with low BMI
      (OR = 2.02, 95% CI: 1.13-3.59). Out of other potential factors possibly involved
      in the occurrence of respiratory infections only the presence of chronic
      respiratory symptoms (OR = 2.43, 95% CI: 1.64-3.59), allergy (OR = 1.89, 95% CI:
      1.34-2.66), and Environmental Tobacco Smoke (OR = 1.54; 95% CI: 1.05-2.25)
      increased the susceptibility of children to acute respiratory infections. Central
      heating in the household was shown to have a protective effect (OR = 0.65, 95%
      CI: 0.43-1.00) when compared with children from households where coal or gas was
      used for home heating.

PMID- 9629028
TI  - The change of attitude of Hungarian physicians towards the importance of risk
      factors of coronary heart disease over the period 1985-1996.
AB  - Cardiovascular mortality in Hungary is still increasing, while it shows a
      continual decrease in the developed Western world. The authors examined, by means
      of a questionnaire, the attitude of physicians, in a large county hospital, to
      prevention of cardiovascular diseases and promotion of a healthy way of life. The
      questionnaire was answered by 170 physicians, 107 (63%) males and 63 (37%)
      females. Eighty-six percent of them believed coronary heart disease to be
      preventable. Twenty-six percent of the physicians currently smoked, and 53% did
      not know their own cholesterol level. As a cardiovascular mortality risk factor
      smoking was considered the most important risk factor, with sedentary lifestyle
      the second, high cholesterol level the third, and hypertension being only the
      fourth. Hungarian hospital physicians' rating of the effect of reducing the risk
      factors for coronary heart disease was similar to those results published in 1986
      of American doctors, there being no significant difference in the importance
      attributed to smoking and elevated blood cholesterol. American doctors believed
      that hypertension had a more important effect on coronary heart disease than did
      Hungarian physicians, whilst the Hungarians attributed greater importance to a
      diet high in fat, being overweight, having a sedentary life-style, stress,
      elevated triglyceride level and type A behaviour. The results of this present
      study which related to the doctors attitudes towards health education for their
      patients were compared to results obtained from a study relating to physicians in
      the same hospital in 1985. Only in two aspects was a significant change observed.
      According to the authors' opinion greater efforts should be made regarding
      physician education on the subject of disease prevention. Additionally the
      employment of well educated nurses with specific training in preventive medicine
      could improve the effectiveness of the prevention of coronary heart disease.

PMID- 9629029
TI  - Communicating with the public: community-based nursing research and practice.
AB  - This paper presents examples of community-based nursing research in relation to
      selected health care trends that affect practice and considers ways the media can
      help community health nurses be more effective communicators with the public.
      Research provides evidence that community-based nursing practice includes quality
      services that can control costs; a focus on disease prevention and health
      promotion; the organization of services where people live, work, and learn;
      partnerships and coalitions; service to people across the life span; services to
      culturally diverse populations; access to services for at-risk populations;
      development of the community's capacity for health; work with policy makers for
      policy change; and efforts to make the environment healthier. Two approaches to
      communication with the public through the media, social marketing and media
      advocacy, are compared. It is recognized that community health nurses are well
      prepared and suited for media advocacy. Media advocacy can be used to not only
      communicate the effectiveness of community-based nursing practice but also to
      support the community's voice for public health.

PMID- 9629031
TI  - Benefits and barriers to well-child care: perceptions of mothers in a rural
      state.
AB  - Though preventive health care can be beneficial, many children do not receive
      regular well-child care. To gain insight into the reasons for the underuse of
      well-child care, this qualitative study elicited consumers' views by examining
      how mothers in a rural state perceive well-child care, its benefits, and barriers
      to obtaining it. Twenty-one women in two Wyoming counties were interviewed about
      their knowledge and beliefs about well-child care and the care their children had
      received. Five categories of responses for the definition of well-child care, 10
      categories of benefits, and seven categories of barriers were identified. Most of
      the informants valued well-child as providing maternal reassurance, information,
      identification of problems, developmental testing, preventive care, and health
      maintenance, and would obtain the recommended care if the barriers they
      perceived, such as financial limitations and inconvenience, were removed or
      reduced. Primary care providers can promote the use of well-child care in
      numerous ways, including educating consumers on the purposes, benefits, and
      schedule for preventive care, providing services that consumers value, providing
      high quality care, and providing cues-to-action to promote consumers to make and
      keep appointments.

PMID- 9629030
TI  - A qualitative assessment of inner city elementary school children's perceptions
      of their neighborhood.
AB  - Three hundred seventy-nine youths from an inner city elementary school were
      surveyed to determine their perceptions of their neighborhood. Using a
      qualitative, word association format, older students responded to 20 descriptive
      words (e.g., dirty, safe, quiet, dangerous) while younger youths drew pictures in
      response to three words (safe, sad, happy). Using content analysis techniques,
      findings indicated that the youths found neighborhood areas and residents that
      were perceived as safe, quiet, beautiful, friendly, fun/happy, and helpful.
      However, safety issues and a dirty, noisy neighborhood also emerged as major
      themes. Collaborative initiatives focusing on cleaning up the neighborhood and
      reducing violence are suggested, as are areas of intervention and further
      research.

PMID- 9629033
TI  - Depressive disorders among the Chinese elderly in a suburban community.
AB  - A community survey of depression among the Chinese > or = 65 years in age was
      performed in a suburban setting. One hundred and eighty-seven individuals
      comprised the survey group. Among them, 65 (34.8%) were scored > or = 11 on the
      Chinese version of the Geriatric Depression Scale. Compared with nondepressed
      individuals, those with depressive disorders were more likely to be older and
      with poor family support. Forward stepwise logistic regression analysis
      identified only age as significantly correlating with geriatric depression
      scores.

PMID- 9629032
TI  - Prostate cancer education in African American churches.
AB  - The use of churches as recruitment sites of African Americans into health
      promotion activities is a popular theme in the 1990s literature. This research
      measured the impact of previous exposure to cancer on participation in an
      educational program and a free prostate cancer screening. Cues to action from the
      Health Belief Model provided the conceptual framework. Over 500 men attended a
      prostate cancer educational program at their church. Men who participated in the
      educational program and completed the questionnaire were given a voucher that
      they could take to their doctor of choice for a free prostate cancer examination.
      Having a member of the congregation who was previously diagnosed with cancer was
      a significant cue to attendance at the educational program (P = 0.03).
      Recommendations for future cancer screening in churches are given.

PMID- 9629035
TI  - Population-based public health nursing interventions: a model from practice.
AB  - In a changing and complex health care system, public health nurses face
      challenges to explain their work and contributions to health outcomes. In
      response to this need, the Minnesota Department of Health, Section of Public
      Health Nursing, initiated a process to describe public health nursing
      interventions. The Public Health Nursing Interventions (PHI) Model was developed
      through a collaborative process by public health nurses at the state and local
      levels. The purpose of the model was to define more clearly the practice of
      public health nursing and to describe better the work of public health nurses at
      the community and systems levels. The PHI model identifies 17 interventions and
      provides practice examples at the systems, community and individual/family
      levels. The model defines a broader view of the mission and scope of public
      health nursing. Practice examples are given for agency staff, administrators,
      educators, and policy makers.

PMID- 9629034
TI  - Severity of abuse to pregnant women and associated gun access of the perpetrator.
AB  - To investigate the relationship between abuse to pregnant women and gun access by
      the abuser, an ethnically stratified cohort of 199 pregnant abused women (70
      African-Americans, 63 non-Hispanic Anglo-American, and 66 Hispanic women were
      interviewed using: (1) The Index of Spouse Abuse, a measure of the severity of
      physical and nonphysical abuse; (2) The Danger Assessment Scale, a measure of
      potential danger of homicide; and (3) The Severity of Violence Against Women
      Scale, a measure of threats of violence and actual violence. There were no
      significant differences by ethnicity among the 41.2% of the abused women who
      reported that their male partner had access to a gun. Among these same women
      reporting gun access, 17% reported the abuser kept the gun on his body. Women
      reporting gun access by the abuser reported higher level of abuse on all scaled
      instruments (P = < 0.01). To protect women's safety and prevent further trauma
      and potential homicide, routine assessment for abuse and gun access is
      recommended. Additionally, policy initiatives to remove firearms from abuse
      perpetrators may reduce the severity of violence experienced by abused women.

PMID- 9629036
TI  - Comox Valley Nursing Centre: from collaboration to empowerment.
AB  - The Comox Valley Nursing Centre was initiated as a two year demonstration project
      by the Registered Nurses Association of British Columbia (RNABC) and funded by
      the Ministry of Health. The purpose of the project was to demonstrate innovative
      nursing practice in a primary health care context. Findings from the project were
      expected to inform provincial health care planning, nursing scope of practice,
      and health and nursing policy development. A free standing nursing center was
      planned and implemented through a collaborative effort by RNABC, nurses and
      community residents. An external team of researchers evaluated the project using
      a variety of methods, including participatory action research. During the project
      an innovative nursing practice, based on principles of collaboration, developed
      and has continued during the extended provincial and regional funding of the
      Centre. Drawing from the evaluation findings, case studies and using Henneman,
      Lee and Cohen's (1995) concept analysis of collaboration, this paper describes
      how the principles of collaboration were actualized or suppressed. The paper
      examines how collaboration impacted empowerment for nurses, clients and the
      community. Lessons learned about the reciprocal relationships between
      collaboration and empowerment, implications for nursing practice, and how the
      approach can contribute to a better understanding of the impact of collaborative
      practice approaches on health care delivery are discussed.

PMID- 9629037
TI  - Home health nurses' initial experiences with wireless, pen-based computing.
AB  - Eight home health nurses from the Visiting Nurse Service of New York participated
      in a focus group discussion after their initial experiences using wireless, pen
      based computing in the inner-city, home care environment. Transcripts of the
      nurses' responses to open-ended questions were analyzed and central themes were
      found, following the method of concept analysis described by Strauss and Corbin
      (1990). The central concepts were "Readiness," "A thousand pounds on my back,"
      "Call for support," "Problems with transmission," "Using the computer as an
      assistant," "Nurses discovered glitches," and "Everybody has to have a computer."
      These themes reflected the nurses' initial experiences with the wireless
      computers and also revealed their concerns. This article will describe these
      themes and will discuss the implications of current improvements in wireless
      computing for health care. The focus group themes aided in understanding how this
      group of experienced home health nurses began to transition from handwriting on
      several different forms to checking-off items on a small, hand-held computer
      screen, from innovating methods to communicate when telephones were not
      available, to using a wireless computer to send and receive data involved in the
      patient admission process

PMID- 9629038
TI  - Doctors who smoke: can physician tobacco use constitute impairment?

PMID- 9629039
TI  - The choice is ours. Ethical actions under managed care.

PMID- 9629040
TI  - Hidden contract zingers. What you don't know about Medicare payment formulas can
      hurt you.

PMID- 9629041
TI  - Choice versus efficiency. OB/Gyn access bill raises questions about patient
      freedom.

PMID- 9629042
TI  - At loggerheads in Laredo.

PMID- 9629043
TI  - Suffering in silence. Victims of elder abuse rarely ask for help.

PMID- 9629044
TI  - The anatomy of success. Texans are generously donating their bodies to science.

PMID- 9629045
TI  - [Treatment strategy in first traumatic anterior dislocation of the shoulder. Plea
      for a multi-stage concept of preventive initial management].
AB  - The purpose of this paper is to outline the treatment protocol for the first time
      traumatic anterior shoulder dislocator, with options including conservative,
      arthroscopic and open surgical treatment. Regarding the subclassification of the
      first time traumatic anterior dislocater, it is imparitive to differentiate
      between the unidirectional dislocator with and without hyperlaxity. This
      subclassification takes into account the structural quality of the stabilizing
      ligamentous structures of the glenohumeral capsule. The patient with hyperelastic
      ligaments exhibit elastic deformation of the glenohumeral ligaments at the time
      of dislocation and thus, sustain less interstitial structural damage to the
      ligament. Therefore, these patients benefit from non-operative treatment. There
      are extrinsic and intrinsic factors which determine the outcome of the primary
      traumatic anterior shoulder dislocation. Extrinsic factors are those that are not
      related to changes in the shoulder morphology. The most important extrinsic
      factor is the age of the patient at the time of injury. The younger the patient
      at the time of injury the greater the risk of recurrence. As a rule, those
      patients 25 years of age or less, at the time of initial injury are less likely
      to spontaneously stabilize without surgical intervention, than they are to
      develop recurrence. Secondly, the type and level of sport participation is
      related to recurrence. Although the severity of the trauma can not be quantified,
      it certainly has an influence on recurrence. Immobilization remains
      controversial. A rehabilitation program is more likely to be successful in
      atraumatic instability. Patient compliance is important regardless of the type of
      treatment selected. Intrinsic factors include injury to the various anatomic
      structures about the shoulder, occurring at the time of primary anterior shoulder
      dislocation. A deep Hill Sachs lesion is more likely to result in recurrence
      secondary to both the impaction of the bone, as well as, the reduction of the
      area of articular surface. A displaced bony Bankart is a highly unstable
      situation secondary to the loss of the butress to retain the humeral head. In
      contrast to a Hill Sachs lesion or a bony Bankart, a concomittent fracture of the
      greater tuberosity is unlikely to result in recurrent dislocation. Isolated
      laberal detachment is not related to recurrence, but a complete disruption of the
      laberal ligament complex is highly correlated with recurrence. A rare subluxation
      erecta, as a special form of traumatic inferior instability, has a high
      recurrence rate. With increasing age there is a higher risk of concomittent
      rotator cuff tear. In most situations surgical repair of the rotator cuff tear
      results in resolution of the instability. The essential issue in determining the
      treatment protocol is to define concomittent hyperlaxity in the injured shoulder.
      Concomittent hyperlaxity precludes initial surgical treatment. The orthopedic
      surgeon treating the patient at the time of injury needs to design a concise
      treatment protocol for the patient based on the assessment of the extrinsic and
      intrinsic factors. An unreducable shoulder dislocation or associated vascular
      injury requires emergent intervention. Absolute indications for surgical
      treatment include: persistent dislocation, bony Bankart, a grossly displaced
      greater tuberosity fracture, and rupture of the subscapularis tendon. Surgical
      stabilization of primary anterior traumatic dislocation is indicated if the
      following strict criteria are met: adequate trauma, no self reduction,
      unidirectional instability without hyperlaxity, Hill Sachs lesion, age below 26
      years, high level of sport activity and the special situation of luxatio erecta.
      Post primary stabilization is indicated for persistent subluxation, subjective
      instability or demonstrated pathologic instability tests. Rotator cuff tears due
      to traumatic dislocation in the elderly population require surgical repair.

PMID- 9629046
TI  - [Retrograde nailing of humerus shaft fractures with the unreamed humerus nail. An
      international multicenter study].
AB  - Combined with the new unreamed humeral nail (UHN) (Synthes), the retrograde
      approach to the endomedullary canal of the humeral shaft promises careful
      reduction and fixation of humeral shaft fractures. This prospective multicenter
      study reports and analyses 102 retrograde nailings with the UHN and their
      operative procedures. Seven patients with pathological fractures have died
      meanwhile, but 75 patients could be followed up until bone healing. Seventy-three
      fresh humeral shaft fractures, 12 pseudarthrosis, 3 refractures and 14
      pathological fractures have been treated with the UHN. In 98 cases (96.1%) the
      surgeon estimated fracture stability well enough to initiate immediate
      postoperative elbow and shoulder mobilization. The difficulties involved with
      free-hand interlocking proximally at the nail tip in 5.9%, fissure or avulsion at
      the insertion point in 3.9% and radial nerve palsy also in 3.9% of the cases were
      the most important intraoperative complications. In all 75 patients followed up,
      bone healing occurred, but five fractures (6.7%) needed more than 8 months
      connected with a second operative procedure. In one case spongious bone
      transplantation and new locking bolts had been performed. In three cases a
      special compression device has been used, whereas in one case also a new nail and
      in the second spongious bone transplantation had been added. In the fifth case
      plate osteosynthesis had been performed. At the end of treatment 89.4% of the
      patients had excellent shoulder function and 88.0% excellent elbow function. Once
      the indication for surgery is established, the UHN can be considered a reliable
      and safe implant for stabilizing humeral shaft fractures.

PMID- 9629047
TI  - [Intraoperative ultrasound study of thoracolumbar spinal fractures with spinal
      canal fragments. Determining canal width and anatomic control of decompression:
      comparative analysis with CT].
AB  - Intraoperative ultrasonography is recommended for operations on the thoracolumbar
      spine to complement the information provided by standard X-ray, intensifier
      screen or myelography. There are no unanimates opinions concerning the impaction
      or exeresis of these fragments. The aim of this study was to show the advantages
      of intraoperative ultrasonography for anatomic determination and control of the
      maneuvers used. This study included 46 cases with fractures from T11 to L2.
      Ultrasonography was performed during the intraoperative reduction provided by the
      installation and the pedicular instruments. The authors stress the limits of the
      anatomic and geographic determination, as well as tilting of the fragments
      because of the size of the ultrasonographic head. The quality of the exeresis may
      be falsely interpreted in the presence of fragments with a section of less than 4
      mm, lateralized, double fragments or in the presence of massive intraoperative
      haemorrhage. Analysis of the impaction results is more complicated because all of
      these fragments displaced themselves secondarily. The ligamentum communis
      vertebralis posterior has no anatomical containing role. The tilting before the
      impaction and the state of the overlying intervertebral disk represent essential
      factors for failures. Ultrasonography is better than intraoperative myelography.
      Nevertheless, it still needs to be complemented by intraoperative profile X-rays
      and a very precise preoperative CT scan of the intervertebral disk lesions
      analysis of complicated cases (fragments with residual pedicular attachments-
      type A 3.1.2.; T-like fractures--type A 3.2.1.).

PMID- 9629048
TI  - [Amputation or reconstruction of IIIB and IIIC open tibial fracture. Decision
      criteria in the acute phase and late functional outcome].
AB  - In IIIB and IIIC type open tibial fractures (according to Gustilo) the primary
      decision that has to be made regarding therapy is wether or not the limb can be
      salvaged. To standardize the criteria for amputation different salvage scores
      have been established in recent years. In this study the Hannover Fracture Scale
      (HFS), the Predictive Salvage Index (PSI), the Mangled Extremity Severity Score
      (MESS) and the NISSSA score were evaluated regarding their clinical relevance.
      When ROC Analysis was performed for all these scores in our patients the HFS
      revealed the highest sensitivity (0.91), but low specificity (0.71). The highest
      specificity was noted for the MESS (0.97), which in parallel showed the lowest
      sensitivity (0.59). In general it seems to be essential to make the right
      decision initially in order to avoid secondary amputation. All the scores
      mentioned here appear to be helpful in decision making. Salvaged limbs in IIIB
      and IIIC fractures presented a comparable good outcome, whereas salvaged IIIC
      injuries with a high score presented an outcome which was as bad as in secondary
      amputations. Secondary amputated patients required not only significant longer
      hospitalization but also resulted in poor outcome compared with the patients
      having received reconstruction or primary amputation.

PMID- 9629049
TI  - [Callus distraction of femur and tibia. Experiences with the mono-fixateur-
      indications for procedural changes].
AB  - In a 4-year period, 18 patients underwent callus distraction of the femur or
      tibia with the use of a unilateral external fixator. Twelve patients had post
      traumatic bone loss resulting from complex lower-limb fractures. The bony defect
      was located in the tibia in 11 cases and in the femur in one case. All patients
      had major associated soft-tissue lesions. The length of the bony defect averaged
      6.25 cm. Eight fractures were infected at the beginning of treatment. Six other
      patients underwent callus distraction for reasons of limb shortening. Five femora
      and one tibia were lengthened. The average increase in length was 6.5 cm. There
      were no fixator-related complications during distraction. The rate for the
      lengthening and consolidation phase was 49 days for 1 cm of length. Complications
      consisted of angulatory deformities in 6 cases, infections in four cases,
      fractures at the docking site in four cases and a fracture of the callotasis in
      one case. Nine patients underwent reosteosynthesis: planned secondary nailing
      after callus distraction was carried out in six patients. Three patients
      underwent plating at the docking site. The follow-up examination after bone
      transport showed a good-to-excellent outcome in 7 out of 11 patients. The outcome
      was satisfactory in 4 cases. Results after limb lengthening were good to
      excellent in all cases. The unilateral external fixator is, in our opinion, a
      convenient stabilization device and permits appropriate bone transportation for
      distraction osteogenesis. Alignment control during distraction, however, was
      difficult to manage in some cases. At the time of docking, reosteosynthesis by
      intramedullary nailing represents a viable alternative for further external
      fixation if the limb is free of infection.

PMID- 9629050
TI  - [Resorbable rods and screws for fixation of ankle fractures. A randomized
      clinical prospective study].
AB  - A prospective randomized clinical trial was performed to evaluate the use of self
      reinforced absorbable composites (Biofix) in the fixation of ankle fractures. The
      aim of this study was to demonstrate that fixation with Biofix rods and screws is
      as good as the standard A.O. fixation. The benefits of Biofix rods and screws
      are: a reduction in costs since no secondary operation is needed, prevention of
      stress-shielding and thereby diminishing the risk of bone porosity. Patients aged
      between 16 and 75 years old with closed, non-comminuted fractures of the lateral
      and/or medial malleolus and dislocation of the fracture fragments greater than 2
      mm were included in the study. 22 patients were treated with Biofix rods and
      screws and the control group of 19 patients with a standard technique. After 3, 6
      and 12 months, rontgenograms were taken. At the same time functional results were
      evaluated following the criteria of Olerud and Molander. Two patients were
      withdrawn from the trial for non-medical reasons. 22 patients (12 from the Biofix
      group, 10 from the AO group) operated two or more years ago were contacted to see
      if any complications had occurred since they were last seen. In 4 cases a Biofix
      screw broke down just beneath the head during insertion. This did not result in
      an insufficient fixation of the fracture. There were no early post-operative
      complications. The functional and rontgenological results in both groups were
      equal. In three cases a sterile sinus developed at the site of screw insertion.
      Biofix rods and screws, made of polylactic acid, are a good alternative for the
      fixation of fractures of the ankle. The use of resorbable fracture fixation
      material has the advantage that a second operation to remove osteosynthesis
      material is not necessary. The long term results are good. There is, however, a
      possibility of development of tissue reaction to the resorbable material.

PMID- 9629051
TI  - [Changes in crystallinity by sterilization and processing of ultrahigh molecular
      polyethylene used in endoprosthetics].
AB  - PURPOSE OF THE STUDY: We wanted to analyze crystallinity changes during
      sterilization in raw and in UHMWPE components for total joint arthroplasty
      manufactured. MATERIALS AND METHODS: To analyze the crystallinity DSC
      measurements and to determine the relative crystallinity infrared spectroscopy
      was performed. The DSC measurements were based on a comparison between the
      melting enthalpy of one known material to the unknown material. RESULTS: The raw
      manufactured non-sterilized sample showed a value for the DSC-measured
      crystallinity of 55.5%; the sample after gamma-sterilization without air was
      56.0%, and with air 56.5%. The crystallinity after ethylene-oxide sterilization
      was 57.7% and after autoclavation 57.9%. The manufacturing time from the raw to
      the arthroplasty part showed some what different results. The average
      crystallinity of the samples differed between 55.4% and 61.6%. The best results
      were achieved in ETO-sterilized samples and one gamma-sterilized sample without
      air. The highest values were seen for the Hylamer. CONCLUSION: In summary, the
      best values for crystallinity were seen in both raw and completed arthroplasty
      products with ETO sterilization. For medical use cancerogenous factors must be
      excluded. Gamma-sterilization without air can be accepted as well. Increasing the
      crystallinity too much can lead to more wear debris.

PMID- 9629052
TI  - [Pediatric polytrauma. A retrospective comparison between pediatric, adolescent
      and adult polytrauma].
AB  - Numerous epidemiological studies about multiple trauma patients do not include an
      analysis of patients under the age of 18. To study this, the data of 682 patients
      with multiple traumata, treated between 1981 and 1991 at Hannover Medical School,
      Germany, were retrospectively analyzed. The patients were divided into four age
      related groups: preschool age (< 6 years), school age (< 13 years), teenagers (<
      18 years) and adults (> or = 18 years). Analyzed were the cause of trauma,
      localization of injuries and the cause of death. Children were less often injured
      as passengers in cars, but more often injured as pedestrians and bicyclists than
      adults. However, children showed a significant higher mortality than adults, with
      threefold increased risk of death when they injured as passengers in car
      accidents. In all groups injuries to the head and the legs were most common.
      Children showed a lower incidence of trauma to the thorax, abdomen, hip and arms
      than the adult group. Nevertheless, trauma to the thorax, abdomen and head was
      associated with the highest risk of death in all groups. Spinal cord injuries,
      especially injuries to the neck, also showed a high risk of death. Children
      younger than 6 years had the most severe head injuries. Safety improvements for
      children in cars, helmet usage on bicycles and early training in traffic safety
      for children might decrease the lethality in this group of trauma patients.

PMID- 9629053
TI  - [Tibial pilon fracture].

PMID- 9629054
TI  - [Unusual gunshot injuries].
AB  - When patients with gunshot injuries are medically treated, it is also important
      to examine the wound itself to achieve further information concerning the
      distance and direction from where the bullet was fired. Besides that, it must be
      remembered that the bullet does not necessarily penetrate the target in a linear
      direction, but there can be various curves and angles in the bullet channel and
      subsequently adjacent organs injured.

PMID- 9629055
TI  - [Bilateral dislocation fracture of the head of the humerus. Arthroplasty and/or
      arthrodesis].
AB  - Functional recovery after bilateral comminuted fractures of the humeral head with
      posterior dislocation is poor. When reposition and internal fixation fail, the
      remaining alternatives are (hemi)arthroplasty and/or arthrodesis. In a 50-year
      old patient, we treated the dominant shoulder by arthrodesis; a Neer prosthesis
      was inserted at the other side. Using this strategy, the advantages of both
      techniques were combined with an acceptable functional recovery, which ist
      especially important for young and active patients.

PMID- 9629056
TI  - [Osseous avulsion of the ischio-crural muscle group with concomitant sciatica].
AB  - Avulsion fractures of the ischial tuberosity are rare. They are often caused by a
      typical "splits"-like accident. In general the patients feel sudden severe pain
      in the buttock with localized tenderness in the region of the ischial tuberosity,
      rarely in combination with sciatic nerve irritation. According to the functional
      anatomy, flexion of the knee and extension of the hip may be impaired.
      Roentgenograms often reveal no abnormality and show no evidence of fracture.
      Therefore, inadequate therapy because of missed diagnosis can result in avoidable
      persistent pain. We report on a 42-year-old man with an avulsion fracture of the
      ischial tuberosity. The epidemiology, symptoms, including irritation of the
      sciatic nerve, differential diagnoses, diagnostic procedures and therapy are
      presented in detail.

PMID- 9629057
TI  - [Therapeutic effects of beclomethasone dipropionate enemas on colon damage of
      inflammatory bowel disease model rats].
AB  - The effects of beclomethasone dipropionate (BDP) enemas on ulcerative colitis
      were investigated by administrating BDP enemas to Fischer male rats with an
      inflammatory bowel disease induced by 2,4,6-trinitrobenzensulfonic acid (TNB).
      After administration of a TNB ethanol solution to rats, diarrhea and melena were
      found in all rats, and the wet tissue weights of the colons in the rats increased
      by erosion and thickness of epithelial mucous membranes with edema. BDP enemas
      were administered to the rats one time a day at a dose of 20 or 50 micrograms of
      BDP for 4 or 11 days from the day 3 after TNB treatment, respectively. After
      dosing of BDP, the rate of rats developing diarrhea and melena decreased more
      with time in comparison with that of BDP-free rats, and the symptoms of all rats
      developing the diseases were improved on the day 4 after administration of a dose
      of 50 micrograms of BDP. A dose dependent recovery in the wet tissue weights and
      scores of damages, and the myeloperoxidase (MPO) activity in the tissue were
      found at the early days (until the day 4). However, their measurements on the day
      11 at each dose of BDP were not different from those of control rats
      significantly, as the damages in the colons of the control rats were recovered
      naturally with time. In conclusion, the clinical usefulness of BDP enemas was
      supported by elucidating the dose dependent effect of BDP at the early days in
      the model rats with an inflammatory bowel disease induced by TNB.

PMID- 9629058
TI  - [Scavenging activity of furan derivatives against hydroxyl radical generated by
      Fenton system].
AB  - As the continuation of the work on the antioxidant properties of furan
      derivatives, we have studied hydroxyl radical (OH.) scavenging activity of
      dimethylfuran (DMF) and diphenylfuran (DPF), which are well-known as an effective
      scavenger of singlet oxygen, by an ESR spin trapping technique. The incubation
      mixture of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as a spin trapping agent with
      FE2+ and H202 in 50% acetonitrile aqueous solution gave 1:2:2:1 line signals
      characteristic of DMPO-OH spin adduct. The additions of furan derivatives to the
      incubation mixture decreased the intensity of the DMPO-OH spin adduct signal in a
      dose-dependent manner. The activities of furan derivatives were in the order of
      DMF > DPF > furan. The decrease in the intensity of the signals was not due to
      the inhibition of OH. generating system itself and the destruction of the spin
      adduct by furan derivatives. By comparison with the common OH. scavengers, DMF
      and DPF were found to scavenge OH. more effectively than dimethylsulfoxide and
      mannitol. These results indicate that DMF and DPF can act as a OH. scavenger as
      well as a singlet oxygen scavenger.

PMID- 9629059
TI  - [Study on the "signal" constituents for the evaluation of animal crude drugs. V.
      The "signal" constituents for the identification of Lumbricus in cold medicines].
AB  - Lumbricus has been widely used as an antifebrile agent in cold medicines. The
      identification of each agent, especially crude drugs in formulations, is very
      important from the viewpoint of quality control. In this paper, the contents of
      amino acids, organic acids, nucleic acid components and cholesterol were
      investigated to evaluate the "signal" constituents of Lumbricus and Lumbricus
      extracts in the medicines. It was found that the content pattern of these
      components of Lumbricus extracts was almost the same as those in Lumbricus
      itself. However, most of other crude drugs used in cold medicines, also contain
      some of these components. It was difficult to identify Lumbricus through the
      difference in the content pattern of these components. Therefore, we focused on
      such five constituents as cholesterol, lombricine, lactic acid, inosine and
      hypoxanthine, because lombricine is a characteristic amino acid of Lumbricus and
      the contents of other four components in Lumbricus are relatively high compared
      with those of other crude drugs. Lombricine and inosine were detected clearly in
      all seven commercial formulations investigated, and cholesterol and hypoxanthine
      were also detected except two commercial formulations. However, the detection of
      lactic acid was not successful in all formulations, because of the presence of
      interfering components. In the seven commercial cold medicines, lombricine and
      inosine were found to be useful as "signal" constituents for the identification
      of Lumbricus in cold medicines.

PMID- 9629061
TI  - [Preparation of optically active succinic acid derivatives. III. Regioselective
      condensation reactions of optically active 2-substituted succinic acids with
      diimidazolide].
AB  - We investigated the large scale synthesis of monocalcium bis [(2S)-2-benzyl-3
      (cis-hexahydroisoindolin-2-ylcarbonyl) propionate] dihydrate (KAD-1229), which
      has a potent hypoglycemic effect, in a single reaction vessel. (2S)-2-Benzyl-3
      (cis-hexahydroisoindolin-2-ylcarbonyl) propionic acid (7) was directly obtainable
      from (S)-2-benzylsuccinic acid (2) and cis-hexahydroisoindoline (4), without the
      isolation of intermediates by the method using thionyldiimidazole (9) and/or
      diimidazolide of the acid 2. Sequential reaction of imidazole with thionyl
      chloride, 2, and 4, followed by acid catalyzed hydrolysis gave amidecarboxylic
      acid 7 in 86% overall yield. The acid 7 was treated with 2 N NaOH, followed by
      the treatment with calcium chloride to give KAD-1229 in 91% yield.

PMID- 9629060
TI  - [Inhibitory effects of shimotsu-to, a traditional Chinese herbal prescription, on
      ultraviolet radiation-induced cell damage and prostaglandin E2 release in
      cultured Swiss 3T3 cells].
AB  - We have investigated the effects of Shimotsu-to, a traditional Chinese herbal
      prescription (Kampo medicine), on ultraviolet (UV) radiation-induced cell damage
      and prostaglandin E2 (PGE2) release in cultured Swiss 3T3 cells to examine the
      anti-inflammatory mechanism of Shimotsu-to. Short-term UV irradiation
      significantly induced cell damage and stimulated PGE2 release in Swiss 3T3 cells
      cultured for 4 h. The UV-radiation-induced cell damage and the stimulation of
      PGE2 release were significantly suppressed by the treatment with Shimotsu-to.
      Among the single crude drug components of Shimotsu-to, Rehmanniae Radix showed
      significant protective effects against UV-radiation-induced cell damage and PGE2
      release. Other synthetic anti-inflammatory agents, such as dexamethasone,
      dipotassium glycyrrhizinate and allantoin also protected against UV-induced cell
      damage and inhibited PGE2 release in cultured Swiss 3T3 cells. These results
      suggest that the anti-inflammatory mechanism of Shimotsu-to against UV-irradiated
      erythema (acute skin inflammation) in guinea pigs in vivo may be mediated by the
      inhibition of PGE2 release from cutaneous target cells.

PMID- 9629062
TI  - Pushing and pulling in relation to musculoskeletal disorders: a review of risk
      factors.
AB  - The objective was to review the literature on risk factors for musculoskeletal
      disorders related to pushing and pulling. The risk factors have been described
      and evaluated from four perspectives: epidemiology, psychophysics, physiology,
      and biomechanics. Epidemiological studies have shown, based on cross-sectional
      data, that pushing and pulling is associated with low back pain. Evidence with
      respect to complaints of other parts of the musculoskeletal system is lacking.
      Risk factors have been found to influence the maximum (acceptable) push or pull
      forces as well as the physiological and mechanical strain on the human body. The
      risk factors have been divided into: (a) work situation, such as distance,
      frequency, handle height, and cart weight, (b) actual working method and
      posture/movement/exerted forces, such as foot distance and velocity, and (c)
      worker's characteristics, such as body weight. Longitudinal epidemiological
      studies are needed to relate pushing and pulling to musculoskeletal disorders.

PMID- 9629063
TI  - The influence of exercise and dehydration on postural stability.
AB  - The aim of this study was to investigate the effects of exercise-induced and
      thermal dehydration on postural balance. Eight male subjects cycled for 2 h at a
      power output equal to 57-63% VO2max on two different occasions: once without
      drinking (NF) and once with intake of 1.9 l of a carbohydrate-electrolyte
      solution (FR). Before and after the exercise test, the velocity of the centre of
      pressure (COP) excursion was measured on a force platform during 30-s bipedal
      standing in normal position, feet side by side, and tandem position, feet heel to
      toe. On another occasion, eight subjects underwent seven consecutive sauna
      sessions (85 degrees C, 50% rh) of 15 min duration with no fluid replacement (S)
      to induce thermal dehydration. Mean fluid loss was 2.7 (+/- 0.4)%, 0.5 (+/- 0.5)%
      and 3.0 (+/- 0.6)% of body mass after NF, FR and S, respectively. Mean velocity
      of COP excursion after the exercise test was significantly higher in the NF than
      in the FR trial (p < 0.05). Postural stability was not influenced by S. In
      conclusion, prolonged exercise without fluid ingestion seems to negatively affect
      postural stability, whereas no effect is observed after exercise with fluid
      replacement or after thermal dehydration.

PMID- 9629064
TI  - Effect of semi-rigid lumbosacral orthosis use on oxygen consumption during
      repetitive stoop and squat lifting.
AB  - The use of back belts in industry has increased despite the lack of scientific
      evidence supporting their efficacy. The purpose of this study was to investigate
      the effect of a semi-rigid lumbosacral orthosis (SRLSO) on oxygen consumption
      during 6-min submaximal repetitive lifting bouts of 10 kg at a lifting frequency
      of 20 repetitions min-1. Fifteen healthy subjects (13 men, two women)
      participated in this study. Each subject performed squat and stoop lifting with
      and without an SRLSO for a total of four lifting bouts. Lifting bouts were
      performed in random order. Oxygen consumption during the final minute of each
      lifting bout was used for analysis. A two-way analysis of variance with repeated
      measures was used to analyse the effects of lift and belt conditions. The stoop
      and squat methods were significantly different, with the squat lift requiring 23%
      more oxygen on average than the stoop lift for equal bouts of work. No
      significant difference was found between the belt and no belt condition within
      the same lifting technique and no interaction was present. These data suggest
      that an SRLSO does not passively assist the paravertebral muscles (PVM) in
      stabilizing the spine during submaximal lifting bouts.

PMID- 9629065
TI  - Method and performance: two elements of work technique.
AB  - In the present study work technique was viewed in two basic elements: the method
      of carrying out a work task and the individual performance of the work task. The
      aim was to investigate how eight selected kinematic, kinetic, electromyographic
      and psychophysical variables can characterize the two elements of work technique.
      Twelve female subjects lifted a box using two methods, back and leg lifts, and
      two different simulated performances, fast and slow lifts. Motions, ground
      reaction forces, muscle activity in the lower back and perceived exertion were
      measured. A dynamic biomechanical model was applied. The trunk angular
      displacement and velocity clearly separated the lift methods. The trunk angular
      velocities and accelerations, the L5/S1 moments and the EMG variables were
      closely related to the performances. The work technique varied between the
      subjects to a greater extent than the individual variability over repetitions of
      a lift task. A larger inter-individual variability for kinematic variables was
      mostly shown in leg lifts compared with back lifts. The EMG patterns displayed
      differences in muscle activation that were not revealed by the kinematic or
      kinetic patterns. The results imply that separate variables should be used for
      descriptions of work methods and task performances; for method descriptions
      ranges of motion seem to be appropriate, for performance descriptions
      displacement time derivatives and load variables seem to be more useful.
      Moreover, the inter-individual differences suggest that work technique should be
      evaluated on an individual level.

PMID- 9629066
TI  - Spine loading during asymmetric lifting using one versus two hands.
AB  - This study documented three-dimensional spinal loading associated with asymmetric
      lifting while using either one or two hands to perform the task. Lift asymmetry
      was defined as a function of the load origin relative to the sagittal plane of
      the body. Lifts occurred at 0, 30, or 60 degrees off the sagittal plane on both
      sides of the body (lifting from the right and from the left relative to the
      sagittal plane). Ten subjects lifted a 13.7 kg box from one of these origins to a
      sagittally symmetric destination. Spinal loads were estimated through the use of
      a validated EMG-assisted model. Spine compression and lateral shear forces
      increased as the lift origin became more asymmetric. However, spinal compression
      and lateral shear increased by about twice the rate when lifting from origins to
      the left of the sagittal plane compared to lifting from origins to the right of
      the sagittal plane. Anterior-posterior spinal shear decreased as asymmetry
      increased with larger decreases occurring when lift origins occurred to the right
      of the sagittal plane. One-hand lifting changed the compression and shear
      profiles significantly. One-hand lifts using the hand on the same side of the
      body as the load resulted in compression forces that were approximately equal to
      those observed when lifting with two hands in a sagittally symmetric position.
      Anterior-posterior shear decreased and lateral shear increased under these
      conditions. These results reflect the trade-offs that must be considered among
      spinal forces during asymmetric lifting while using one or two hands. These
      findings have significant implications for task assessment interpretation and
      workplace design.

PMID- 9629067
TI  - Trunk strength in combined motions of rotation and flexion/extension in normal
      young adults.
AB  - Thirty-eight normal healthy young subjects (14 males, 24 females) with mean ages
      of 23 years (males) and 21 years (females), performed 36 functional rotational
      tasks of the trunk. The subject's lower extremities were stabilized in a
      stabilizing platform, allowing the entire motion of flexion-rotation and
      extension-rotation to take place in the trunk. Of these tasks, 18 were isometric
      and the other 18 were isokinetic. The isometric tasks consisted of flexion
      rotation and extension-rotation from a 20 degrees, 40 degrees and 60 degrees
      flexed trunk in 20 degrees, 40 degrees and 60 degrees of axial rotation. The
      isokinetic activity consisted of flexion-rotation and extension-rotation from
      upright and flexed postures respectively in 20 degrees, 40 degrees and 60 degrees
      rotation planes at 15 degrees, 30 degrees and 60 degrees/s angular velocities.
      The results revealed that the males were significantly stronger than females (p <
      0.01) and isometric activities produced significantly greater torque compared to
      isokinetic efforts (p < 0.01). The degree of trunk flexion was not significant;
      the angle of rotation, although significant, had only a small effect. The 60
      degrees trunk rotation was significantly different from 20 degrees and 40 degrees
      of trunk rotation. The multiple regressions were all significant (p < 0.01);
      however, they predicted only 40 to 60% of the variations. Based on the results
      and analysis, it is suggested that the motion involved rather than the torque may
      have a consequential effect in the precipitation of back injuries.

PMID- 9629068
TI  - Measurement variability and sincerity of effort: clinical utility of isokinetic
      strength coefficient of variation scores.
AB  - Although the use of measures of strength variability as a means of judging
      sincerity of effort is becoming common practice, the accuracy of doing so has
      been questioned. Coefficient of variation (CV) cut-off points, indicating the
      upper limit of variability for repeated maximal efforts, are routinely used to
      identify workers providing submaximal efforts during various strength tests.
      However, the stability of the CV itself has not been considered when comparing an
      individual's observed CV score to these cut-off points. The purpose of the
      present study was to examine the day-to-day variability of the CV calculated from
      maximal isokinetic knee extension efforts, and to describe how this measurement
      error affects the accuracy of the CV as a distinguishing criterion between
      maximal and submaximal efforts. Thirty-one healthy males (mean age 25 +/- 4.5
      years) completed three maximal and three submaximal isokinetic knee extension
      efforts on two separate occasions. Although submaximal CVs were significantly
      greater than maximal CVs (15.6 versus 3.7%; p < 0.01), there was considerable
      overlap between submaximal and maximal CV frequency distributions. More
      importantly, an individual observed CV could vary +/- 3.1% as a result of day-to
      day variation or measurement error. This range in possible CV scores should be
      considered when comparing an individual's score to proposed cut-off points. Since
      individual CVs vary considerably from day-to-day, and since precise cut-off
      values distinguishing between maximal and submaximal conditions cannot be
      identified, CV scores must be interpreted cautiously, and the potential errors in
      relying extensively on this approach to identifying insincere efforts should be
      recognised.

PMID- 9629069
TI  - Directional stimulus-response compatibility: a test of three alternative
      principles.
AB  - The basis of directional stimulus-response compatibility was studied using a task
      in which 128 participants moved a cursor into targets with a joystick, resembling
      the operation of certain industrial and construction equipment. Compatible and
      incompatible versions of three alternative compatibility principles were compared
      in all combinations. Visual Field (VF) compatibility was present if cursor and
      controlling limb movement were in the same direction in the visual field, Control
      Display (CD) compatibility meant that the control motion was in the same
      direction as, and parallel to, cursor motion, and Muscle Synergy (MS)
      compatibility was defined as use of the muscle synergy normally associated with
      the required direction as seen in the visual field. VF-compatible conditions had
      significantly shorter reaction, movement and homing times, and fewer reversal
      errors, for males and females, in two testing sites. These advantages were
      maintained over practice. VF compatibility was confirmed as a robust spatial
      compatibility principle that is affected by neither the orientation of the
      operator's limb or head nor the muscle synergy used in executing the task. It
      offers not only more rapid performance, but also a markedly reduced rate of
      potentially dangerous directional errors. The relationship between this finding
      and theoretical aspects of stimulus-response compatibility is discussed.

PMID- 9629070
TI  - Pulling force in lateral lifting and lowering.
AB  - This work investigated maximal voluntary lateral hand pulling force in 18
      healthy, habitually active men. Measurements were made in standing at different
      static angles of lateral trunk flexion, as well as at different constant lifting
      and lowering velocities. Movement was constrained to the frontal plane, velocity
      was controlled by an isokinetic dynamometer, pulling force was measured with a
      strain gauge and overall lateral angular displacement of the trunk by an
      electrogoniometer. Mean peak pulling force values ranged from 478 to 658 N
      (static), 291 to 528 N (lifting), and 801 to 911 N (lowering), respectively. The
      static pulling forces were the highest in flexed positions to the loaded side (10
      degrees and 20 degrees trunk angles). In lifting, peak and position-specific
      pulling force decreased with increasing velocity. Peak lifting force occurred in
      a flexed trunk position of 7 to 9 degrees to the loaded side. In lowering,
      pulling forces were significantly higher than during lifting at corresponding
      velocities and showed less changes with velocity. Peak lowering force occurred at
      a trunk angle of -7 to -11 degrees, that is towards the unloaded side. In
      conclusion, maximal voluntary pulling force in the frontal plane was found to be
      task dependent. Lowering was accompanied by higher forces and a different
      velocity and position dependency than lifting which, in addition to the fact that
      the trunk muscles act predominantly eccentrically during the lowering task, may
      impose an increased risk of injury.

PMID- 9629071
TI  - The self in transformation: the passage from a two- to a three-dimensional
      internal world.
AB  - This paper seeks to describe some of the steps in the process of transformation
      from a two-dimensional to a three-dimensional inner world as experienced by a
      patient who had essentially used up her remaining vital resources. An important
      hurdle had first to be crossed when the analyst was required to demonstrate her
      capacity to survive with her in a two-dimensional claustrum, in a solitary
      confinement. Here, an oppositional defensive system had been created in which
      positive and negative personifications of vital but withdrawn energies ensured
      that she was locked within an interior world that sought to bar entry to anyone
      else, and where the possibility of the transformation of her self was disallowed.
      The patient had to accept the risk of breaching the system of self-defence before
      the analyst was allowed a mutual position within her interior world. A series of
      dreams tracks this transformation internally and in relation to the analyst.

PMID- 9629072
TI  - The body in analysis: authentic movement and witnessing in analytic practice.
AB  - This paper will describe a form of active imagination called authentic movement,
      in which attention is given to the somatic unconscious. In authentic movement,
      patients are encouraged to focus inward and attend to any bodily sensations,
      images and feelings which may arise. In the process of focusing inward on one's
      bodily-felt experience, images, somatic memory and the accompanying feelings
      which arise are then available to be explored as a communication from the
      patient's unconscious. Authentic movement supports the individual in linking
      image with affect in that the individual re-experiences the somatic aspect of
      symbolization. What was previously conserved on the somatic level as unmentalized
      experience, can now begin to be taken up into the mind, thought about, and made
      available for analysis. In authentic movement, the analyst acts as a silent
      witness to the patient's explorations. The quiet focused attention of the witness
      helps to create a secure containing environment in which the person moving can
      experience a sense of feeling held and seen. The function of the witness is to
      hold the patient's experience in his own mind, particularly what is not yet
      mentalized. The witness utilizes his somatic countertransference, including any
      images, feelings and bodily responses which are generated by what is being
      communicated non-verbally, as a means of understanding and responding to the
      patient's material.

PMID- 9629073
TI  - States of identity: a perspective drawing upon Fordham's model and infant
      studies.
AB  - This paper examines the Jungian concept of identity and distinguishes it from
      projective identification and participation mystique, which also refer to
      nondifferentiation between self and object but involve projective mechanisms.
      Clinical work by Fordham and a psychoanalytic infant observation are used to
      illustrate early perceptual operations defined by experimental researches. These
      operations are understood to be expressions of the primary self which manifest
      themselves before the structuring necessary for normal projective identification.
      This paper attempts to describe an intersubjective experience between mother and
      baby that allows for their separate ways of relating, but does not depend on
      projective mechanisms that can exist only after there has been adequate
      development.

PMID- 9629074
TI  - The super-ego, the voice of the self and the depressive position.
AB  - The Freudian concept of the super-ego and Jung's idea of a primary moral reaction
      in the unconscious--the voice of the self--are compared. From its origin the
      superego is connected with human destructiveness, but for Jung individual
      conscience is based on a collision between the ego and the inner world of
      archetypes. With reference to Neumann's 'New Ethic', some implications of Jung's
      idea of the unconscious ambiguity of good and evil are discussed. Finally an
      attempt is made to relate the concept of the primary moral reaction to a
      developmental and clinical framework, notably Klein's depressive position, but
      only a partial integration is possible.

PMID- 9629075
TI  - International ties that bind.

PMID- 9629076
TI  - Cocaine exposure in utero.

PMID- 9629077
TI  - How aging affects pain management.

PMID- 9629078
TI  - It never hurts to check. Taking the time to read a label benefited this migraine
      sufferer.

PMID- 9629079
TI  - Ethics in the trenches. Decision making in practice.

PMID- 9629080
TI  - Asthmatic arrest.

PMID- 9629081
TI  - Microvascular complications of diabetes. Nursing assessment and intervention.

PMID- 9629082
TI  - Emergency! Cervical spine injury.

PMID- 9629083
TI  - Managed care: the value you bring.

PMID- 9629084
TI  - Clinical snapshot: trigeminal neuralgia.

PMID- 9629085
TI  - Holistic modalities & healing moments.

PMID- 9629086
TI  - Basic assessment series. A review of the adult musculoskeletal system.

PMID- 9629088
TI  - Quality managed care: a nursing perspective.

PMID- 9629087
TI  - Tears have no color. The medical world is not always prepared for the collision
      of cultures.

PMID- 9629089
TI  - Nursing presence in osteoporosis research.

PMID- 9629090
TI  - Making decisions about premature infants.

PMID- 9629091
TI  - Meeting Ben. Offering your presence can make a world of difference to even the
      most difficult patient.

PMID- 9629092
TI  - ANA examines privatization, for-profit conversions.

PMID- 9629094
TI  - More on breast cancer guidelines.

PMID- 9629093
TI  - Overcoming managed care's quick fix.

PMID- 9629095
TI  - More on breast cancer guidelines.

PMID- 9629096
TI  - More on breast cancer guidelines.

PMID- 9629097
TI  - More on breast cancer guidelines.

PMID- 9629098
TI  - More on breast cancer guidelines.

PMID- 9629099
TI  - More on breast cancer guidelines.

PMID- 9629100
TI  - More on breast cancer guidelines.

PMID- 9629101
TI  - This list works. Use it.

PMID- 9629102
TI  - Getting prepared for rural practice.

PMID- 9629103
TI  - Hospital bean-counting.

PMID- 9629104
TI  - Studying workplace health.

PMID- 9629105
TI  - Mercury levels in the Cree population of James Bay, Quebec, from 1988 to 1993/94.
AB  - BACKGROUND: High levels of mercury in the Cree population of James Bay, Que.,
      have been a cause of concern for several years. This study examines changes in
      mercury levels within the Cree population between 1988 and 1993/94 and identifies
      potential determinants of high mercury levels. METHODS: Data on mercury levels
      among the Cree were obtained through a surveillance program undertaken by the
      Cree Board of Health and Social Services of James Bay. In 1988 and again in
      1993/94 surveys were carried out in all 9 Cree communities of northern Quebec.
      Hair samples were obtained and analysed for mercury content. Analyses were
      carried out to determine the proportion of people who had mercury levels in
      excess of established norms. Changes in mercury levels between 1988 and 1993/94
      and determinants of high levels were estimated by means of regression methods.
      RESULTS: The proportion of the Cree population with mercury levels in excess of
      15.0 mg/kg declined from 14.2% in 1988 to 2.7% in 1993/94. Wide variations in
      mercury levels were observed between communities: 0.6% and 8.3% of the Eastmain
      and Whapmagoostui communities respectively had mercury levels of 15.0 mg/kg or
      greater in 1993/94. Logistic regression analyses showed that significantly higher
      levels of mercury were independently associated with male sex, increasing age and
      trapper status. There was a correlation between the mercury level of the head of
      the household and that of the spouse. INTERPRETATION: Mercury levels in the Cree
      of James Bay have decreased in the recent past. Nevertheless, this decrease in
      mercury levels may not be permanent and does not necessarily imply that the issue
      is definitively resolved.

PMID- 9629107
TI  - The hepatitis C disaster.

PMID- 9629106
TI  - Evidence-based guidelines for universal counselling and offering of HIV testing
      in pregnancy in Canada.
AB  - OBJECTIVE: To provide Canadian health care workers with evidence-based guidelines
      for universal counselling about HIV testing and the offering of such testing to
      all pregnant women. OPTIONS: Universal counselling and offering of HIV testing to
      all pregnant women versus targeted testing of only pregnant women at high risk
      for HIV infection. Antiretroviral treatment protocols for HIV-positive mothers
      and their infants are discussed as the intervention to reduce mother-to-child
      transmission rates. OUTCOMES: Main outcomes are mother-to-child HIV transmission
      rates and consequences of HIV testing on the mother and infant. EVIDENCE:
      Articles published from January 1985 to March 1997 identified through a MEDLINE
      search; articles published in pertinent medical journals in 1996 and 1997
      identified through a manual search; and abstracts presented at international
      HIV/AIDS conferences. BENEFITS, HARMS AND COSTS: Early diagnosis of HIV infection
      in a pregnant woman optimizes her medical and psychosocial care, decreases the
      incidence of mother-to-child transmission and decreases the risk of horizontal
      transmission to sexual partners. New, third-generation HIV tests have reduced
      false-positive rates and thus diminished the harm of screening. RECOMMENDATIONS:
      A screening strategy consisting of universal counselling and offering of HIV
      testing is recommended for all pregnant women in Canada (grade B recommendation).
      Targeted testing of only pregnant women at high risk for HIV infection fails to
      identify a substantial proportion of HIV-positive pregnant women and is therefore
      not recommended (grade D recommendation). Women who identify themselves as being
      at high risk and whose initial HIV test result is negative should be counselled
      about the reduction of high-risk behaviours and retested in 6 months (grade B
      recommendation). Treatment of seropositive women and infants with zidovudine to
      prevent mother-to-child transmission is recommended (grade A or B recommendation
      depending on gestational age and CD4 count). VALIDATION: These guidelines are
      endorsed by the Canadian Pediatric AIDS Research Group and are in agreement with
      the recommendations of the Canadian Paediatric Society and the US Public Health
      Service Task Force.

PMID- 9629108
TI  - Hepatitis C as medical misadventure.

PMID- 9629109
TI  - Methylmercury and fish consumption: weighing the risks.

PMID- 9629110
TI  - Determinants--and determination.

PMID- 9629111
TI  - Access to prenatal HIV testing.

PMID- 9629112
TI  - Defining the physician's duty to warn: consensus statement of Ontario's Medical
      Expert Panel on Duty to Inform.
AB  - Ontario's Medical Expert Panel on Duty to Inform was formed to consider the duty
      of Ontario physicians in circumstances where a patient threatens to kill or cause
      serious bodily harm to a third party. The panel was concerned about the
      implications of any duty to inform on the integrity of the physician-patient
      relationship, particularly with respect to confidentiality. The panel agreed that
      regulations safeguarding the confidentiality of patient information ought to be
      changed only if there is a critical reason for doing so, but, after deliberation,
      the panel members concluded that the need to protect the public from serious risk
      of harm is a paramount concern that should supersede the duty of confidentiality.
      The recommendations reported here were endorsed in principle by the panelists and
      the groups they represented (the Royal College of Physicians and Surgeons of
      Canada, the Canadian Medical Protective Association, the College of Physicians
      and Surgeons of Ontario, the Ontario College of Family Physicians and the Ontario
      Medical Association) and are being implemented by the College of Physicians and
      Surgeons of Ontario.

PMID- 9629113
TI  - Unconventional therapies for cancer: 5. Vitamins A, C and E. The Task Force on
      Alternative Therapies of the Canadian Breast Cancer Research Initiative.

PMID- 9629114
TI  - Injuries associated with the farm harvest in Canada.

PMID- 9629115
TI  - Concern mounts as transfusion medicine loses its lustre.
AB  - Transfusion medicine is in trouble. Several factors, ranging from the tainted
      blood scandal to changes in the way the system operates, mean that young
      physicians are avoiding the specialty. Dr. Antonio Giulivi of the Red Cross says
      the issue is serious because these specialists act as the system's overseers, and
      this fact won't change when the Red Cross gets out of the blood business in
      September.

PMID- 9629116
TI  - In your face: a new wave of militant doctors lashes out.
AB  - Doctors in 4 Canadian provinces have chosen to use job action and other militant
      approaches as leverage to encourage governments to improve health care and
      funding. CMAJ asked physicians why this is happening now.

PMID- 9629117
TI  - Dr. Luigi Di Bella and the politics of elixirs.
AB  - Health Canada and the Canadian-Italian Physicians Association recently spent
      $20,000 to send 4 Canadian cancer specialists to Italy to check out the "miracle"
      anticancer cocktail prepared by an Italian physician. Most doctors remain
      decidedly sceptical about this latest "cure," but Charlotte Gray says their
      suspicions count for little when an issue like this captures the imagination of
      the public and their politicians.

PMID- 9629118
TI  - A Marathon session: a town's MDs develop a philosophy to call their own.
AB  - Last June CMAJ described how Marathon--a remote town in Northern Ontario--had
      gone from medical rags to riches in just over a year (CMAJ 1997;156:1593-6). Once
      chronically underserviced in terms of physician services, this community of 5500
      people went from a single overworked doctor to a group practice of 7 physicians.
      The change involved far more than numbers, however. The Marathon solution was
      built on a philosophy of physician sustainability and long-term retention, not
      just recruitment. The change was designed to ensure that the town could finally
      get off the roller-coaster ride that saw more than 75 doctors come--and go-
      during the previous 10 years. A year after its initial report, CMAJ returned to
      see if the Marathon experiment was still working.

PMID- 9629119
TI  - With HIV prevalence among women increasing, more provinces encourage prenatal
      testing.
AB  - Testing of pregnant women for antibodies to HIV remains a thorny medical and
      ethical issue. On the one side are children who stand to benefit if their
      mothers' HIV status is determined. On the other is women's right to determine
      what tests they will receive. A majority of provinces now have counselling
      programs in place to encourage women to undergo testing. However, testing remains
      voluntary and informed consent is required before a test is done--policies that
      have CMA support.

PMID- 9629120
TI  - Little-publicized Manitoba case holds crucial lesson for doctors.

PMID- 9629121
TI  - Internet virology 101.

PMID- 9629122
TI  - Projected physician supply.

PMID- 9629123
TI  - Clopidogrel for reduction of atherosclerotic events.

PMID- 9629124
TI  - Tolcapone for Parkinson's disease.

PMID- 9629125
TI  - The Crystal Ear hearing aid.

PMID- 9629126
TI  - The kallikrein-kinin system: evolution of form and function.

PMID- 9629127
TI  - Precursor convertases: an evolutionary ancient, cell-specific, combinatorial
      mechanism yielding diverse bioactive peptides and proteins.

PMID- 9629128
TI  - Molecular evolution of ligand-binding specificity in the vasopressin/oxytocin
      receptor family.

PMID- 9629129
TI  - Evolution of the neuropeptide Y family and its receptors.

PMID- 9629130
TI  - Comparative aspects of dopaminergic neurotransmission in vertebrates.

PMID- 9629131
TI  - Neuropeptides in the lungfish brain: phylogenetic implication.

PMID- 9629132
TI  - Cholinergic regulation of the pituitary: autoexcitatory control by acetylcholine
      of melanotrope cell activity in Xenopus laevis.
AB  - In the studies on Xenopus laevis presented here, the role of acetylcholine (ACh)
      in the regulation of pituitary activity was examined. The results are discussed
      in connection with other results on cholinergic regulation of pituitary
      functioning in vertebrates. It is demonstrated that dissociated melanotropes can
      synthesize ACh in vitro. In addition, immunocytochemical studies show the
      presence of the ACh-synthesizing enzyme choline acetyltransferase (ChAT) in the
      cytoplasm of melanotrope cells. ACh concentration-dependently raises the
      intracellular free calcium concentration as well as the release of
      proopiomelanocortin (POMC)-derived peptides. Selective muscarinic receptor
      antagonists showed that the actions of ACh are mediated through an M1-subtype
      muscarinic receptor. Immunofluorescence cytochemistry visualized muscarinic
      receptors on the surface of melanotrope cells. It is concluded that ACh
      stimulates the release of POMC-derived peptides from the Xenopus melanotrope cell
      in an autocrine, excitatory way. Finally, the possible mechanism through which
      ACh is released from melanotrope cells and the physiological significance of ACh
      in the pituitary gland are discussed.

PMID- 9629134
TI  - Control of peripheral thyroid hormone levels by activating and inactivating
      deiodinases.

PMID- 9629133
TI  - A protein tyrosine kinase modulates GABAA receptor in frog pituitary melanotrope
      cells.

PMID- 9629135
TI  - Nonviral gene transfer for studying signaling in comparative developmental
      biology.

PMID- 9629136
TI  - Physiological importance of the T3 mitochondrial pathway.

PMID- 9629137
TI  - Identification of G protein-coupled receptors in insect cells.

PMID- 9629138
TI  - The control of expression of chicken and human estrogen receptor genes.

PMID- 9629139
TI  - Regulation of the progesterone receptor functions.

PMID- 9629140
TI  - Evolution and diversification of the nuclear receptor superfamily.

PMID- 9629141
TI  - Functional significance of ecdysteroid diversity in arthropods.

PMID- 9629142
TI  - Studying amphibian metamorphosis by in vivo gene transfer.

PMID- 9629143
TI  - Structure, function, and regulation of insulin-like growth factors in fish.

PMID- 9629145
TI  - Regulation of chicken muscle growth by insulin-like growth factors.

PMID- 9629144
TI  - Peculiarities of insulin secretion in chickens.

PMID- 9629146
TI  - Interaction of lactogenic hormones with prolactin receptors.

PMID- 9629147
TI  - Isolation and characterization of the chicken insulin receptor substrate 1 gene.

PMID- 9629148
TI  - Lipolytic effects of beta 1-, beta 2-, and beta 3-adrenergic agonists in white
      adipose tissue of mammals.

PMID- 9629149
TI  - Differential effects of retinoic acid on white and brown adipose tissues. An
      unexpected role for vitamin A derivatives on energy balance.

PMID- 9629150
TI  - Molecular and cellular guidance of neuronal migration in the developing olfactory
      system of rodents.

PMID- 9629151
TI  - Developmental origin of the olfactory system and GnRH neurons in the amphibia.

PMID- 9629152
TI  - The melanin-concentrating hormone system in fish.

PMID- 9629153
TI  - Characterization of the receptor for melanin-concentrating hormone on melanoma
      cells by photocrosslinking.

PMID- 9629154
TI  - Structure, expression, and evolution of the variant MCH gene in primates.

PMID- 9629155
TI  - Morphofunctional changes in melanin-concentrating hormone-producing neurons in
      relation to the control of food and water intake.

PMID- 9629156
TI  - Melanotrope cell heterogeneity in the pars intermedia of amphibians.

PMID- 9629157
TI  - The significance of multiple inhibitory mechanisms converging on the melanotrope
      cell of Xenopus laevis.

PMID- 9629158
TI  - Pregnane steroid modulation of GABAA receptor in frog pituitary melanotrophs.

PMID- 9629159
TI  - Paracrine interactions within the pituitary gland.

PMID- 9629160
TI  - Cell heterogeneity as a reflection of the secretory cell cycle.

PMID- 9629161
TI  - Characterization of somatostatin receptor subtypes in mammalian pituitary.

PMID- 9629162
TI  - Neuroendocrine and local control of the frog testis.

PMID- 9629163
TI  - Proopiomelanocortin gene expression in the ovary of the frog, Rana esculenta.

PMID- 9629164
TI  - Neuroendocrine control of adrenocortical cells by serotonin in amphibians and
      mammals.

PMID- 9629165
TI  - Toward a role for angiotensin-converting enzyme in insects.

PMID- 9629166
TI  - Ecdysiostatins and allatostatins in Schistocerca gregaria.

PMID- 9629167
TI  - Structure of neuropeptide precursors in cnidaria.

PMID- 9629168
TI  - Control of growth and differentiation in bivalve mollusc larvae. Molecular
      characterization of a new factor from the oyster Crassostrea gigas.

PMID- 9629169
TI  - Interacting mitogenic pathways during spermatogonial G1/S-phase traverse in the
      sea star, Asterias vulgaris.

PMID- 9629170
TI  - Post-source decay analysis of neuropeptides.

PMID- 9629171
TI  - Multiple measurements of gene expression in single, living cells enable molecular
      analysis of endocrine cell heterogeneity.

PMID- 9629172
TI  - Analysis of the projections to amphibian pars intermedia by combined tract
      tracing, immunohistochemistry and confocal microscopy.

PMID- 9629174
TI  - Distribution of vasoactive intestinal peptide in the brain and hypothalamo
      hypophysial system of the sea bream (Sparus aurata).

PMID- 9629173
TI  - Interactions between neuropeptide Y, cholecystokinin, galanin, and luteinizing
      hormone-releasing hormone-I in the chicken hypothalamus.

PMID- 9629175
TI  - Primary culture of GnRH neurons derived from the sheep embryo olfactory placode.

PMID- 9629176
TI  - Biochemical characterization and regional distribution of mGnRH and cGnRH-II in
      the spinal cord of the frog Rana ridibunda.

PMID- 9629177
TI  - The GnRH increase following progesterone withdrawal is associated with an
      increased glutamatergic tone in the preoptic area of the ovariectomized ewe.

PMID- 9629178
TI  - Neuropeptide-immunoreactive projections within the caudal area of contact in
      vertebrates as demonstrated by substance P.

PMID- 9629179
TI  - Effect of melatonin on the GnRH release by hypothalamic explants of male mink.

PMID- 9629180
TI  - Differences in second messengers (Ca2+ and cAMP) suggest a dual role for SRIF in
      regulating GH release from porcine somatotropes.

PMID- 9629181
TI  - Feedback inhibition of ovine GH on GH release from the pituitary of rainbow
      trout.

PMID- 9629182
TI  - Metabolic effects of ovine growth hormone in a teleost, Anabas testudineus.

PMID- 9629183
TI  - Neuroendocrine control of frog adrenocortical cells by calcitonin gene-related
      peptide.

PMID- 9629184
TI  - Involvement of pituitary adenylate cyclase-activating polypeptide in the
      regulation of frog adrenal steroidogenesis.

PMID- 9629185
TI  - Photoperiodic control of the seasonal variations in the daily pattern of
      melatonin synthesis in the European hamster, Cricetus cricetus.

PMID- 9629186
TI  - Molecular cloning of the pigment dispersing hormone in a crustacean.

PMID- 9629187
TI  - Biosynthesis of neuroandrogens in the frog brain.

PMID- 9629188
TI  - Changes in the activity of antioxidant enzymes in the rat brown adipose tissue
      induced by 6-OHDA and insulin.

PMID- 9629189
TI  - Comparative distribution of pituitary adenylate cyclase-activating polypeptide
      and vasoactive intestinal polypeptide immunoreactivity in the chicken forebrain.

PMID- 9629190
TI  - Relationship between melanotrope cell heterogeneity and background adaptation in
      the frog intermediate lobe.

PMID- 9629191
TI  - VGF-like immunoreactivity in amphibian hypothalamo-hypophysial system.

PMID- 9629192
TI  - BRCA1 gene expression in reproductive and endocrine tissues in adult cynomolgus
      monkey.

PMID- 9629193
TI  - Mesotocin gene expression and evidence of gene duplication in the tammar wallaby.

PMID- 9629194
TI  - Cosecretion of prolactin and growth hormone by the pituitary of the bullfrog.

PMID- 9629195
TI  - Inhibitory and stimulatory control of proopiomelanocortin biosynthesis in the
      intermediate pituitary of Xenopus laevis.

PMID- 9629196
TI  - Release of glycosylated and non-glycosylated forms of somatolactin by fish
      pituitary culture in vitro.

PMID- 9629197
TI  - A novel peptide generated from the C-terminal extension of trout
      proopiomelanocortin-A.

PMID- 9629198
TI  - Localization of amidating enzymes (PAM) in frog (Rana temporaria) endocrine
      pancreas.

PMID- 9629199
TI  - Partial identification of a new pheromonotropic peptide from Mamestra brassicae.

PMID- 9629200
TI  - Cloning of neuropeptide Y, peptide YY, and peptide Y from sea bass (Dicentrarchus
      labrax), a marine teleost.

PMID- 9629201
TI  - A second somatostatin gene is expressed in the brain of the frog Rana ridibunda.

PMID- 9629202
TI  - The leech angiotensin-converting enzyme.

PMID- 9629203
TI  - Urotensin II in the central nervous system of the frog Rana ridibunda.
      Biochemical characterization and immunohistochemical localization.

PMID- 9629204
TI  - Evidence for the presence of a secretogranin II-related protein in rainbow trout
      pituitary.

PMID- 9629205
TI  - Insulin-like growth factor-1 binding in the ovary of the domestic hen.

PMID- 9629206
TI  - Cloning of the IGF-1 receptor cDNA of turbot (Scophthalmus maximus). Messenger
      expression and polyadenylation status.

PMID- 9629207
TI  - beta-Endorphin binding sites in pars distalis of the frog, Rana esculenta.

PMID- 9629208
TI  - Pituitary adenylate cyclase-activating polypeptide: a key player in male
      reproduction?

PMID- 9629209
TI  - Mechanism of action of endothelin-1 in the frog adrenal gland.

PMID- 9629210
TI  - Intracellular growth hormone receptors in chicken liver.

PMID- 9629211
TI  - Comparative ACTH-stimulated responses in rat and human glomerulosa cells.

PMID- 9629212
TI  - Single cell secretion measurements by amperometry in Xenopus melanotropes.

PMID- 9629214
TI  - Insulin release by islets of Langerhans isolated from dorsal and ventral lobes of
      chicken pancreas.

PMID- 9629213
TI  - Activation of GABAA receptors increases cytosolic calcium concentration in frog
      pituitary melanotropes.

PMID- 9629215
TI  - Growth hormone and insulin-like growth factor-I in inducing vitellogenin
      synthesis by frog hepatocytes.

PMID- 9629216
TI  - Cyclic-AMP egress by the Xenopus neurointermediate lobe elicited by low Ca2+ is
      partly reversed by the phorbolester PMA.

PMID- 9629217
TI  - Detection of c-Myc, c-Fos, and c-Jun-like products in the lizard (Podarcis s.
      sicula) testis.

PMID- 9629218
TI  - Role of nitric oxide synthase and nitric oxide in background adaptation in
      Xenopus laevis.

PMID- 9629219
TI  - Mechanism of action of tachykinins in the frog adrenal gland.

PMID- 9629220
TI  - Neuroendocrine responses in background adaptation.

PMID- 9629221
TI  - Structure-function relationships for equine and human aromatases. A comparative
      study.

PMID- 9629222
TI  - In vitro effect of endozepines on frog adrenocortical cells.

PMID- 9629223
TI  - Androgen regulates expression of androgen receptors in the spinal motoneurons.

PMID- 9629224
TI  - alpha-MSH modulates Fos expression in the paraventricular nucleus and
      hyperalgesia induced by intracerebroventricular administration of interleukin-1
      beta in rats.

PMID- 9629225
TI  - The suprarenal ganglia: origin of the neuropeptide Y innervation of the upper
      part of the uterus in the rat.

PMID- 9629226
TI  - NPF immunolocalization in cockroaches and locusts. Comparison of antisera to
      beetle, tapeworm, and pig NPY/NPF-type peptides.

PMID- 9629227
TI  - Age-related changes in serotonergic and catecholaminergic brain systems in the
      lemurian primate Microcebus murinus.

PMID- 9629228
TI  - Melanin-concentrating hormone in the cock.

PMID- 9629229
TI  - Genomic DNA fragmentation in red blood cells of the bullfrog (Rana catesbeiana)
      during metamorphosis.

PMID- 9629230
TI  - Prolactin and stress response in frog Rana esculenta.

PMID- 9629231
TI  - Overview of the conference and the field.
AB  - The field of neuroimmune interactions is a prime example of interdisciplinary
      research spanning immunology, neurobiology, neuroendocrinology, and behavioral
      sciences. It also exemplifies research from the molecular to the clinical domain.
      The greatest challenge of the field, which this conference seeks to stimulate, is
      research that is at the same time precise, focused, and integrative. Several
      levels of interdisciplinary overlap will be highlighted. At the molecular level,
      neuro- and immune mediator molecules or their receptors may be members of the
      same superfamily or may regulate each other's expression or function. Most
      extensively studied are cytokine-neuropeptide/neurotransmitter interactions,
      including expression of cytokines within the central nervous system and
      production of neuropeptides by immune cells or at inflammatory sites. Advances
      relating cytokine-neurohormone interactions to mechanisms of apoptosis will
      ultimately shed light on the role of neuroimmune interactions in neuronal cell
      death and survival and immune cell selection, processes important in neuronal
      plasticity and immune specificity. At a systems level, advances have been made in
      cross-disciplinary application of modes of thinking. Incorporation of
      neurobiology's appreciation of anatomical organization, endocrinology's temporal
      dimension of neurohormonal secretion, and immunology's understanding of stimulus
      specificity all contribute to a more precise definition of how these complex
      systems interact at multiple levels. More precise understanding of effects of
      disruptions of these communications on disease susceptibility and expression will
      clarify how perturbations of one system, such as stimulation of the
      neuroendocrine stress response, might affect expression of disease in the other,
      such as autoimmune/inflammatory or infectious diseases.

PMID- 9629232
TI  - Opiate inhibition of chemokine-induced chemotaxis.
AB  - Chemokines consist of a family of 8-16-kDa cytokines that are generated very
      early in a wide variety of inflammatory responses and attract leukocytes to local
      sites. At nanomolar concentrations chemokines initiate signal transduction and
      activate leukocytes through seven transmembrane receptors (STM), but higher
      micromolar doses result in homologous desensitizing effects. On the basis of
      reports that opiates have anti-inflammatory effects and also use STM, we have
      investigated the possibility that they may cross-desensitize the response of
      leukocytes to chemokines. We have confirmed previous observations that met
      enkephalin (MET) is chemotactic for human peripheral blood monocytes.
      Furthermore, we observed that preincubation of monocytes or neutrophils with MET
      or morphine prevented their subsequent chemotaxis in response to chemokines (MIP1
      alpha or IL-8). However, MET did not inhibit the chemotactic response of PMN to
      NAP-2, a homologous chemokine that is less potent than IL-8 but cannot be
      desensitized. The inhibitory effect of opiates on chemokine-induced chemotaxis
      was antagonized by naloxone. Since MIP-1 alpha and IL-8, unlike NAP-2, have the
      capacity to desensitize leukocytes, it is possible that opiates, by desensitizing
      some chemokine responses, can suppress inflammatory reactions.

PMID- 9629233
TI  - Corticotropin-releasing hormone and inflammation.
AB  - Corticotropin-releasing hormone (CRH) is a major regulator of the hypothalamic
      pituitary-adrenal axis (HPA) and principal coordinator of the stress response. As
      in stress, intracerebroventricular administration of CRH suppresses the immune
      system indirectly, via glucocorticoid and/or sympathetic system-mediated
      mechanisms. Also, during inflammatory stress, the cytokines TNF alpha, IL-1, and
      IL-6 stimulate hypothalamic CRH and/or vasopressin secretion as a way of
      preventing the inflammatory reaction from overreacting. Recently, CRH receptors
      were described in peripheral sites of the immune system, and CRH was found to
      promote several immune functions in vitro. We demonstrated a direct role of CRH
      in the inflammatory immune process in vivo, by first studying the effect of
      systemic CRH immunoneutralization in an experimental model of carrageenin-induced
      aseptic inflammation in Spague-Dawley rats. We extended these observations to
      other forms of experimental inflammation, including streptococcal cell wall
      polysaccharide- and adjuvant-induced arthritides and peptide R16 (epitope of the
      interphotoreceptor retinoid-binding protein)-induced uveitis in Lewis rats. We
      also studied human disease states, including rheumatoid arthritis, Hashimoto
      thyroiditis, and ulcerative colitis. Inflamed tissues contained large amounts of
      IR CRH, reaching levels similar to those observed in the hypophyseal portal
      system. We also demonstrated the presence of CRH mRNA and CRH receptors in
      inflammatory cells and identified the mast cells as a major immune target for
      CRH. In addition to production by immune cells, the peripheral nervous system,
      including the postganglionic sympathetic neurons and the sensory fibers type C,
      appears to contribute to IR CRH production in inflammatory sites. The production
      of CRH from the postganglionic sympathetic neurons may be responsible for the
      stress-induced activation of allergic/autoimmune phenomena, such as asthma and
      eczema, via mast cell degranulation. Antalarmin, a novel nonpeptide CRH receptor
      antagonist, displaced 125I-labeled ovine CRH binding in rat pituitary, frontal
      cortex, and cerebellum, but not heart, consistent with antagonism at the CRHR1
      receptor. In vivo antalarmin significantly inhibited CRH-stimulated ACTH release
      and carrageenin-induced subcutaneous inflammation in rats. Thus, antalarmin and
      other related compounds that antagonize CRH at the level of its own receptor have
      therapeutic potential in some forms of inflammation directly mediated by type 1
      CRH receptors and promise to enhance our understanding of the many roles of CRH
      in immune/inflammatory reactions.

PMID- 9629234
TI  - Stress, adaptation, and disease. Allostasis and allostatic load.
AB  - Adaptation in the face of potentially stressful challenges involves activation of
      neural, neuroendocrine and neuroendocrine-immune mechanisms. This has been called
      "allostasis" or "stability through change" by Sterling and Eyer (Fisher S.,
      Reason J. (eds): Handbook of Life Stress, Cognition and Health. J. Wiley Ltd.
      1988, p. 631), and allostasis is an essential component of maintaining
      homeostasis. When these adaptive systems are turned on and turned off again
      efficiently and not too frequently, the body is able to cope effectively with
      challenges that it might not otherwise survive. However, there are a number of
      circumstances in which allostatic systems may either be overstimulated or not
      perform normally, and this condition has been termed "allostatic load" or the
      price of adaptation (McEwen and Stellar, Arch. Int. Med. 1993; 153: 2093.).
      Allostatic load can lead to disease over long periods. Types of allostatic load
      include (1) frequent activation of allostatic systems; (2) failure to shut off
      allostatic activity after stress; (3) inadequate response of allostatic systems
      leading to elevated activity of other, normally counter-regulated allostatic
      systems after stress. Examples will be given for each type of allostatic load
      from research pertaining to autonomic, CNS, neuroendocrine, and immune system
      activity. The relationship of allostatic load to genetic and developmental
      predispositions to disease is also considered.

PMID- 9629235
TI  - Hormones, pregnancy, and autoimmune diseases.
AB  - Hormonal factors linked to age, gender, and reproductive status are undoubtedly
      involved in regulating the onset of numerous autoimmune diseases. For example,
      systemic lupus erythematosus (SLE), a disease characterized by immune complex
      mediated pathology linked to excess Th2 cytokine production (e.g., IL-10)
      primarily affects women in the reproductive years. Rheumatoid arthritis (RA), a
      disease characterized primarily by cell-mediated joint immunopathology linked to
      deficient Th2 cytokine production, is also more common in women, but, in contrast
      to SLE, the highest incidence is at menopause. Pregnancy-associated changes in
      these diseases, however, provide the most compelling evidence that hormonal
      factors play a major role in modulating the expression of these diseases. SLE
      often flares during pregnancy, whereas RA commonly remits during pregnancy and
      flares or initially develops in the postpartum period. These observations appear
      to be explained by the accumulating data indicating that during pregnancy cell
      mediated immune function and Th1 cytokine production (e.g., IL-12, interferon
      gamma) are suppressed, and humoral immunity and Th2 cytokine production (e.g., IL
      4, IL-10) are enhanced. These patterns reverse in the postpartum period. In other
      words, antithetical Th1/Th2 cytokine profiles appear to characterize pregnancy
      and the postpartum period. Strong evidence now indicates that changes in the
      production of cortisol, progesterone, and estrogen play a major role in
      modulating Th1/Th2 cytokine balance.

PMID- 9629236
TI  - The interleukin-1 system: receptors, ligands, and ICE in the brain and their
      involvement in the fever response.
AB  - The ligands and the receptors of the interleukin 1 (IL-1) system constitute a
      highly inducible set of proteins whose expression in infection and inflammation
      is of key importance in the host defense. The IL-1 system participates in the
      stimulation of the immune system, the neuroendocrine system, and the neuroimmune
      system. The major soluble and secreted agonist of the system, IL-1 beta, has been
      studied by mutational and transgenic approaches. Furthermore, involvement of the
      signal-transducing type I IL-1 receptor (IL-1RI), in fever and other responses,
      has been studied by null mutation technique. We describe the inducible expression
      of the two agonists, IL-1 alpha (31 kDa and 17 kDa) and IL-1 beta (17 kDa) and of
      the IL-1 receptor subtypes IL-1RI and IL-1RII in the brain and in the adrenals
      (as well as in the pituitary cell line AtT20). We also describe an additional
      member of the IL-1 family: the IL-1 receptor antagonist (IL-1ra), an endogenous
      antagonist to IL-1 alpha and IL-1 beta. Furthermore, the IL-1 beta-converting
      enzyme (ICE) and its differential regulation and expression in brain and adrenals
      is also discussed. Fever is a systemic response to intraperitoneal (i.p.) or
      intracerebroventricular (i.c.v.) injection of IL-1 alpha or IL-1 beta. IL-1 beta
      induced fever can be blocked by IL-1ra pretreatment. The fever response seems to
      be mediated via the IL-1RI as inferred from studies with receptor subtype
      specific mutants of IL-1 beta and from studies in IL-1RI knock-out (IL-1RI KO)
      mice. IL-1 beta knock-out mice showed a hyperresponsive fever to both IL-1
      agonists, IL-1 alpha and IL-1 beta, as well as to LPS.

PMID- 9629237
TI  - Contribution of the ICE family to neurodegeneration.
AB  - The ICE family of cysteine proteases mediates necrotic or apoptotic events in the
      nervous system as well as in other tissues. This suggests that inhibitors may be
      of therapeutic value in acute and, perhaps, chronic neurodegenerative disease. In
      addition, some members of this family may respond to intercellular signals
      controlling proliferation or differentiation. This possibility should be kept in
      mind as therapeutics are pursued.

PMID- 9629238
TI  - Interleukin-1-induced plasticity of hypothalamic CRH neurons and long-term stress
      hyperresponsiveness.
AB  - Infections and endotoxin (LPS) can affect hypothalamic CRH neurons and activate
      the HPA system. This can be prevented by IL-1 receptor antagonist and mimicked by
      IL-1. Chronic activation of the HPA system by repeated or chronic administration
      of IL-1 (1 week) to rats is associated with plastic changes in hypothalamic CRH
      neurons. Single administration IL-1 beta (5 micrograms/kg i.p.) to male Wistar or
      Lewis rats induced a similar form of neuroplasticity 1-3 weeks later. This is
      characterized by a selective increase in coproduction, costorage, and cosecretion
      of AVP in hypothalamic CRH neurons. Exposure of IL-1-primed rats 1-2 weeks later
      to foot shocks or IL-1 resulted in exaggerated ACTH and CORT responses as
      compared to vehicle-primed controls. Thus, rats are hyperresponsive to stressors
      weeks after IL-1 exposure. In IL-1-primed animals, CRH binding and CRH- and V1b
      receptor mRNA levels in the pituitary glands are not altered by IL-1 exposure 2
      weeks earlier. We conclude that IL-1-induced, long-lasting hyperresponsiveness to
      stressors is primarily caused by functional alterations in the brain that may be
      directly related to observed plasticity of hypothalamic CRH neurons.

PMID- 9629239
TI  - Neuroimmunomodulation by macrophage migration inhibitory factor (MIF).
AB  - Recent studies have led to the discovery of a mediator that appears to act as an
      endogenous hormone to counterregulate glucocorticoid action within the immune
      system. Isolated as a product of anterior pituitary cells, the structure of this
      protein was found to be that of macrophage migration inhibitory factor (MIF)--one
      of the first cytokines to be identified and described originally as a T
      lymphocyte factor that inhibited the random migration of macrophages. Macrophages
      and T cells release MIF in response to glucocorticoids, as well as upon
      activation by various proinflammatory stimuli. Once secreted MIF "overrides" the
      immunosuppressive effects of steroids on macrophage and T-cell cytokine
      production. MIF appears to fill an important gap in our understanding of how the
      host initiates and controls the immune response. Because glucocorticoids are an
      integral part of the host's metabolic "stress" response to infection or tissue
      invasion, the role of MIF is to act at an inflammatory site or lymph node to
      counterbalance the inhibitory effects of steroids on the immune response. Anti
      MIF therapeutic strategies are under development and may prove to be a means to
      increase the immunosuppressive and anti-inflammatory properties of endogenously
      released glucocorticoids, thereby reducing the requirement for steroid therapy in
      a variety of autoimmune and inflammatory conditions.

PMID- 9629240
TI  - Structural and functional impact of the transgenic expression of cytokines in the
      CNS.
AB  - Cytokines are powerful mediators of biologic responses in the CNS and may
      contribute to cellular injury in pathophysiologic states. In order to better
      understand the actions of cytokines in the intact mammalian CNS, a transgenic
      approach was employed that targeted the expression of different cytokines to
      astrocytes in mice. Fusion gene constructs consisting of a GFAP expression vector
      into which was inserted the DNA encoding the cytokines interleukin-6 (IL-6), IL
      3, or TNF-alpha were used to generate transgenic mice. Expression of the
      transgene-encoded cytokines in astrocytes was confirmed at both the RNA and
      protein levels. Transgenic mice were subject to multilevel analysis to determine
      the extent of structural and functional CNS alterations. Transgenic mice
      exhibited distinct adult-onset, chronic-progressive neurological disorders that
      correlated with the level and anatomic distribution of transgene-encoded cytokine
      expression. The principal findings were neurodegeneration and cognitive decline
      due to IL-6 expression, macrophage/microglial-mediated primary demyelination with
      motor disease resulting from IL-3 expression, and lymphocytic
      meningoencephalomyelitis with paralysis induced by TNF-alpha expression. These
      transgenic models (1) indicate that expression of cytokines per se in the intact
      CNS is pathogenic, with cytokine-specific neural cell injury leading to unique
      functional deficits; (2) recapitulate many of the structural and functional
      changes seen in human inflammatory neurological disorders; (3) provide a valuable
      tool for advancing our understanding of the CNS pathobiology of cytokines; and
      (4) offer a unique resource for the development and testing of therapies aimed at
      abrogating the harmful actions of these important mediators.

PMID- 9629241
TI  - The neurotrophins and neuropoietic cytokines: two families of growth factors
      acting on neural and hematopoietic cells.
AB  - Recent progress has revealed similarities between the receptors and signaling
      systems used by neurotrophic factors as compared to other growth factors and
      cytokines. The neurotrophins use a family of receptor tyrosine kinases known as
      the Trk receptors, whereas ciliary neurotrophic factor (CNTF) uses a "cytokine
      receptor" system that shares receptor components with a number of distantly
      related cytokines. We have used a human embryonal carcinoma cell line and human
      leukemia cell lines to examine the actions of the neurotrophins and CNTF on
      cellular differentiation. Our findings demonstrate that specific combinations of
      neurotrophic factors are required to influence the neuronal progenitor cells to
      become postmitotic mature CNS neurons. Such synergistic interactions may play an
      important role in modulating the differentiation of a wide assortment of neuronal
      precursors in the developing nervous system. Furthermore, our studies with
      leukemia cells suggest that neurotrophic factors may play a similar role in
      hematopoietic differentiation and that these factors may have therapeutic
      application in leukemia differentiation.

PMID- 9629242
TI  - Interleukin-3 and interleukin-3 receptors in the brain.
AB  - We have previously demonstrated that interleukin 3 (IL-3) has a neurotrophic
      effect on central cholinergic neurons and have demonstrated the presence of IL-3
      receptor (IL-3R)beta subunits in septal cholinergic neurons by reverse
      transcribed polymerase chain reaction (RT-PCR) and immunohistochemistry. In order
      to confirm that the expressed IL-3R is functional, we conducted experiments to
      show an alpha subunit of IL-3R. The alpha subunit was clearly demonstrated by RT
      PCR in the central cholinergic neuronal hybrid cell line SN6, but not in its
      mother cell line N18TG2, and the expression was slightly upregulated after IL-3
      treatment. Choline acetyltransferase and vesicular acetylcholine transporter
      mRNAs were significantly increased in SN6 after treatment with IL-3.
      Immunohistochemically, IL-3R alpha-positive cells were mainly present in the
      medial septal and basal forebrain region, and the stained cells were similar to
      choline acetyltransferase-positive cells in shape and distribution. The IL-3R
      alpha-positive cells slightly increased two days after fimbria-fornix transection
      and decreased seven days after. These findings suggest that functional IL-3
      receptors are expressed in the central cholinergic neurons and contribute to some
      physiological roles such as the differentiation and maintenance of these neurons.

PMID- 9629243
TI  - Interleukin-1, but not stress, stimulates glucocorticoid output during early
      postnatal life in mice.
AB  - The development of neuroendocrine functions depends not only on genetically
      determined mechanisms but also on phenotypic signals. Some of these signals may
      derive from the immune system. For example, interleukin-1 beta (IL-1 beta)
      stimulates glucocorticoid output during the early postnatal period, and
      administration of this cytokine at birth induces permanent alterations in the HPA
      axis in adulthood. We have extended these studies and found that the
      glucocorticoid response elicited in 5-day-old mice by a low dose of IL-1 beta is
      not desensitized by previous exposure to the cytokine. We have also compared the
      magnitude of the increase in corticosterone levels induced by IL-1 in 3-day-old
      and adult mice to that caused by acute stress. IL-1 beta and acute stress caused
      a comparable increase in corticosterone levels in adult mice. In newborn mice,
      however, IL-1 beta, but not restraint or cold stress, stimulated corticosterone
      output. Thus, IL-1 beta can elicit a corticosterone response during the postnatal
      stress-hyporesponsive period. Furthermore, when the corticosterone levels
      attained following IL-1 beta administration were compared to the basal levels of
      the hormone at a given age, the increase in plasma corticosterone levels was
      several fold higher in newborn than in adult animals. These data, together with
      the long-lasting endocrine effects of cytokine exposure at birth, suggest an
      important role of immune cytokines in the programming of neuroendocrine functions
      during ontogeny.

PMID- 9629244
TI  - Administration of interleukin-1 at birth affects dopaminergic neurons in adult
      mice.
AB  - Interleukin-1 beta (IL-1 beta), a cytokine that plays a relevant role during
      inflammatory and immune processes, can also affect brain neurotransmitters and
      the activity of peripheral sympathetic nerves. Because both brain and peripheral
      catecholaminergic systems in mice are not fully developed at birth, we speculated
      that the development of these systems may be susceptible to modifications when
      mice are exposed to IL-1 beta early in life. Here we report that the
      administration to mice of a low dose of IL-1 beta during the first days of life
      results in a decreased dopamine content in the hypothalamus in adulthood. We also
      show that the dopamine content of the superior cervical sympathetic ganglia was
      reduced in adult mice that were treated with IL-1 beta at birth. No changes in
      noradrenaline content nor in its metabolite MHPG were detected in the brain and
      peripheral sympathetic ganglia of these animals. This indicates that central and
      probably also peripheral dopaminergic neurons are preferentially affected by IL-1
      beta treatment at birth. Collectively, these results indicate that an increased
      production of IL-1 beta during infectious or inflammatory processes in the
      perinatal period may induce long-lasting, probably permanent, alterations in
      central and peripheral neurotransmitter systems.

PMID- 9629245
TI  - Effects of peripheral administration of LPS on the expression of immunoreactive
      interleukin-1 alpha, beta, and receptor antagonist in rat brain.
AB  - The cytokine interleukin-1 (IL-1) appears to play a pivotal role in the
      orchestration of brain-mediated, nonspecific illness symptoms during an
      infection. In the present study, we examine the possibility that IL-1 is produced
      in the central nervous system itself, which may be responsible for the induction
      of brain-mediated responses. Using immunocytochemical techniques, we demonstrated
      that peripheral administration of bacterial endotoxin to rats caused a time- (1.5
      24 hr) and dose-dependent (4 micrograms/kg-2.5 mg/kg) induction of IL 1 beta
      immunoreactivity in cells identified as macrophages in meninges and choroid
      plexus and microglial cells in various brain regions. At 8 hr after endotoxin
      (2.5 mg/kg), immunoreactive IL-1 alpha was observed in the same areas and cell
      types as IL-1 beta. Although no quantitative measurements have been performed, it
      appears that fewer cells express immunoreactive IL-1 alpha than IL-1 beta.
      Furthermore, IL-1ra was found to be constitutively expressed in neurons in the
      paraventricular nucleus and supraoptic nucleus, which is in accordance with mRNA
      data. After administration of endotoxin, we observed no additional cells that
      expressed immunoreactive IL-1ra. We conclude that IL-1 alpha and IL-1 beta
      production in the brain is induced in the same cell types, whereas IL-1ra is
      expressed constitutively by a different cell type--probably neurons.

PMID- 9629246
TI  - Brain neurotransmission during peripheral inflammation.
AB  - It is now well established that an inflammatory challenge as evoked by bacterial
      endotoxin (LPS) induces autonomic, endocrine, and behavioral responses that are
      controlled by the brain. However, detailed information on the neuronal pathways
      and neurotransmitters involved is scarce. We used in vivo microdialysis and
      biotelemetry in rats to monitor hippocampal and preoptic serotonergic and
      noradrenergic neurotransmission, body temperature, and heart rate after an i.p.
      LPS injection. Moreover, free corticosterone levels were measured in the
      dialysates, and behavioral activity was scored by visual observation. Apart from
      a biphasic fever response, tachycardia, elevated free corticosterone levels, and
      sickness behavior, peripheral injection of LPS caused a dramatic increase in
      preoptic extracellular concentrations of noradrenaline, but no effect on
      serotonin in this structure. The increase in preoptic noradrenaline levels
      appears to underlie the first fever phase and may participate in hypothalamic
      pituitary-adrenocorticul axis activation. In contrast, whereas LPS had only a
      moderate effect on hippocampal noradrenaline, a marked increase in hippocampal
      extracellular serotonin levels was found. Use of the interleukin (IL)-1 receptor
      antagonist and the cyclooxygenase inhibitor indomethacine learned that IL-1 and
      prostaglandins are mediators in this response. Our data show that an endotoxin
      challenge results in highly differentiated changes in brain neurotransmission,
      probably subserving the coordinate processing of immune information in circuits
      involved in autonomic, neuroendocrine, and behavioral regulation.

PMID- 9629247
TI  - Central and peripheral mechanisms contribute to the hypoglycemia induced by
      interleukin-1.
AB  - The impact that neuroendocrine effects of cytokines have on general host
      homeostasis is reflected by the profound metabolic changes observed in parallel.
      The effect of interleukin-1 beta (IL-1 beta) on glucose blood levels serves as an
      example. Although IL-1 beta stimulates glucocorticoid output and decreases
      hepatic glycogen content, hypoglycemia is concomitantly detected in adult and
      newborn mice. This effect is observed even during fasting and is probably due to
      increased glucose transport into tissues. Even after a glucose load, IL-1-treated
      animals remain hypoglycemic, suggesting that central mechanisms that control the
      set point of glucose homeostasis are affected. Low doses of IL-1 beta injected
      i.c.v. can also induce hypoglycemia. Furthermore, central blockade of IL-1
      receptors partially inhibits the hypoglycemia induced by peripheral
      administration of IL-1 beta. On the other hand, central depletion of
      catecholamines exacerbates IL-1-induced hypoglycemia. IL-1-mediated effects on
      glucose levels might be directed at providing more energy supply to tissues
      during processes with high metabolic demands.

PMID- 9629248
TI  - Leukemia inhibitory factor regulates proopiomelanocortin transcription.
AB  - Leukemia inhibitory factor (LIF), a pleiotropic cytokine, is expressed in both
      fetal and adult pituitary tissue, and LIF immunoreactivity is found in functional
      human pituitary tumors. LIF induces basal, and augments CRH-induced, POMC mRNA
      and ACTH secretion from AtT20 cells. Therefore, we examined LIF signaling and LIF
      regulation of POMC expression in AtT20 cells. Immunoneutralization studies
      demonstrated the dependence of LIF action on both the specific LIF receptor (35%
      inhibition; p < 0.05) and also the gpl30 affinity converter (41% inhibition; p <
      0.05). These antisera also attenuate basal ACTH secretion without added LIF. LIF
      rapidly induced tyrosyl phosphorylation of both STAT 1 alpha, and STAT beta and
      also induced phosphorylation of a novel STAT 1 alpha related protein p115. LIF
      induced POMC transcription (-706/+64) and strikingly potentiated CRH action (up
      to 18-fold induction). This synergy involved cAMP-dependent pathways, as
      forskolin action was also potentiated by LIF. Deletion of the major CRH
      responsive region in POMC (-323/-166) abolished both CRH and LIF action on POMC
      transcription. Thus LIF action in pituitary corticotrophs is dependent on LIF
      receptor heterodimerisation with gpl30 and involves STAT protein tyrosyl
      phosphorylation. LIF enhances POMC transcription and strongly potentiates the
      well-documented action of CRH on the POMC gene. These results define a
      subcellular mechanism for an immuno-neuroendocrine interface between peripheral
      afferent signals and the HPA axis.

PMID- 9629250
TI  - Role of nitric oxide and alcohol on gonadotropin release in vitro and in vivo.
AB  - Alcohol suppresses reproduction in humans, monkeys, and small rodents by
      suppressing release of luteinizing hormone (LH). The major action is on the
      hypothalamus to decrease release of LH-releasing hormone (LHRH). The release of
      LHRH is controlled by nitric oxide (NO) as determined by in vivo and in vitro
      experiments. The hypothesized pathway is via norepinephrine (NE)-induced release
      of NO from NOergic neurons, which activates LHRH release. We have evaluated
      details of this process in male rats by incubating medial basal hypothalamic
      (MBH) explants in vitro and examining the release of NO and metabolites generated
      by NO that control LHRH release. NE increased release of NO as measured by
      determining the content of the enzyme at the end of the experiment (30 min) by
      adding [14C]arginine to the homogenate and measuring its conversion to
      [14C]citrulline since this is formed in equimolar quantities with NO by NO
      synthase (NOS). Because this increase in content, presumably caused by activation
      of the enzyme by NE, was blocked by the alpha 1 receptor blocker prazosin, it
      appears that alpha 1 receptors activate NOS by increasing intracellular free
      calcium in the NOergic neurons, which combines with calmodulin to activate NOS.
      The release of LHRH induced by nitroprusside (NP), a donor of NO, is accompanied
      by an increase in cyclic guanosine monophosphate (cGMP) in the medium supporting
      the activation of guanylate cyclase by NO. This activation is important in
      releasing LHRH since addition of 8-monobutyryl cGMP also released the peptide.
      Ethanol had no effect on the content of NOS or on the increase in content induced
      by NE, indicating that it did not act on NOS. Earlier experiments indicated that
      prostaglandin E2 (PGE2) was important in releasing LHRH. PGE2 is produced by
      activation of cyclooxygenase by NO since this occurred following addition of the
      NO donor, NP. Not only does NP increase PGE2 release, but it also increases the
      conversion of [14C]arachidonic acid to its metabolites, particularly PGE2, by
      activating cyclooxygenase. NP also activated lipoxygenase as indicated by
      increased release of leukotrienes, which also stimulate LHRH release. Ethanol
      acts at this step, because it completely blocked the release of PGE2,
      leukotrienes, and LHRH induced by NP. Therefore, the results support the theory
      that NE acts to stimulate NO release from NOergic neurons. This NO diffuses to
      the LHRH terminals, where it activates guanylate cyclase, leading to an increase
      in cGMP. At the same time, it also activates cyclooxygenase and lipoxygenase. The
      increase in cGMP increases intracellular free calcium, required for activation of
      phospholipase A2. Phospholipase A2 converts membrane phospholipids into
      arachidonic acid, the substrate for conversion by the activated cyclooxygenase
      and lipoxygenase to PGE2 and leukotrienes that activate the release of LHRH.
      Because alcohol inhibits conversion of labeled arachidonic acid to PGE2 and
      leukotrienes, it must act either directly to inhibit cyclooxygenase and
      lipoxygenase or by some other mechanism which, in turn, inhibits the enzyme. We
      initially believed that the action of alcohol was exerted directly on the LHRH
      terminals; however, our recent experiments indicate that alcohol suppresses LHRH
      release, at least in part, by stimulating beta-endorphinergic neurons that
      inhibit the release of NE, which drives the NOergic release of LHRH.

PMID- 9629249
TI  - Role of nitric oxide in the neuroendocrine responses to cytokines.
AB  - During infection, bacterial and viral products, such as bacterial
      lipopolysaccharide (LPS), cause the release of cytokines from immune cells. These
      cytokines can reach the brain by several routes. Furthermore, cytokines, such as
      interleukin-1 (IL-1), are induced in neurons within the brain by systemic
      injection of LPS. These cytokines determine the pattern of hypothalamic-pituitary
      secretion which characterizes infection. IL-2, by stimulation of cholinergic
      neurons, activates neural nitric oxide synthase (nNOS). The nitric oxide (NO)
      released diffuses into corticotropin-releasing hormone (CRH)-secreting neurons
      and releases CRH. IL-2 also acts in the pituitary to stimulate
      adrenocorticotropic hormone (ACTH) secretion. On the other hand, IL-1 alpha
      blocks the NO-induced release of luteinizing hormone-releasing hormone (LHRH)
      from LHRH neurons, thereby blocking pulsatile LH but not follicle-stimulating
      hormone (FSH) release and also inhibiting sex behavior that is induced by LHRH.
      IL-1 alpha and granulocyte macrophage colony-stimulating factor (GMCSF) block the
      response of the LHRH terminals to NO. The mechanism of action of GMCSF to inhibit
      LHRH release is as follows. It acts on its receptors on gamma-aminobutyric acid
      (GABA)ergic neurons to stimulate GABA release. GABA acts on GABAa receptors on
      the LHRH neuronal terminal to block NOergic stimulation of LHRH release. This
      concept is supported by blockade of GMCSF-induced suppression of LHRH release
      from medial basal hypothalamic explants by the GABAa receptor blocker,
      bicuculline. IL-1 alpha inhibits growth hormone (GH) release by inhibiting GH
      releasing hormone (GHRH) release, which is mediated by NO, and stimulating
      somatostatin release, also mediated by NO. IL-1 alpha-induced stimulation of
      prolactin release is also mediated by intrahypothalamic action of NO, which
      inhibits release of the prolactin-inhibiting hormone dopamine. The actions of NO
      are brought about by its combined activation of guanylate cyclase-liberating
      cyclic guanosine monophosphate (cGMP) and activation of cyclooxygenase and
      lipoxygenase with liberation of prostaglandin E2 and leukotrienes, respectively.
      Thus, NO plays a key role in inducing the changes in release of hypothalamic
      peptides induced in infection by cytokines. Cytokines, such as IL-1 beta, also
      act in the anterior pituitary gland, at least in part via induction of inducible
      NOS. The NO produced inhibits release of anterior pituitary hormones.

PMID- 9629252
TI  - Luteinizing hormone-releasing hormone is a primary signaling molecule in the
      neuroimmune network.
AB  - The brain-pituitary-reproductive axis and the brain thymus-lymphoid axis are
      linked by an array of internal mechanisms of communication that use similar
      signals (neurotransmitters, peptides, growth factors, hormones) acting on similar
      recognition targets. Moreover, such communication networks form the basis and
      control each step and every level of reproductive physiology. This presentation
      highlights the extent to which endocrine, neural, glial, or immunologically
      competent cells may achieve their specific functions using common mechanisms, but
      employing them to different degrees. In particular, this work will focus on LHRH,
      the chief hormone orchestrating reproductive events. Within the thymus LHRH plays
      a unique role of immunomodulator, contributing to the sex-dependent changes in
      immune responsiveness during the estrous-menstrual cycle as well as pregnancy.
      From the recent cloning and sequencing of lymphocyte LHRH, the expression of LHRH
      receptor mRNA in lymphocyte, the transduction mechanisms involved, and the
      steroidogenic sensitivity of the intralymphocyte LHRH system. It would appear
      that this peptide may act as an immunological response modifier in the brain
      pituitary-lymphoid-gonadal axis. The interplay between neuronal, endocrine, and
      immune compartments is further emphasized in the study of LHRH-astroglial
      interactions. Astrocytes are able to manufacture a wide variety of signaling
      agents and can secrete immunoregulatory molecules that influence immune cells, as
      well as the glial cells themselves. Astroglia and the immortalized hypothalamic
      LHRH (GT1-1) neurons communicate with an array of mechanisms, via soluble
      mediators as well as cell-to-cell contacts. Manipulation of astroglial-derived
      cytokines and nitric oxide (NO) in GT1-1 neuron-astroglia cocultures, underscores
      a potential cross-talk between different intra/inter-cellular mediators in the
      dynamic control of LHRH release. Further studies aimed to disclose at a
      biochemical and a molecular level such bidirectional, informative network will
      give us new insights into more general issues concerned with the malfunction of
      the neuroendocrine-immune axis.

PMID- 9629251
TI  - The role of IL-6 type cytokines and their receptors in bone.
AB  - Substantial evidence indicates that the IL-6 type of cytokines have profound
      effects on bone metabolism by regulating osteoclast and osteoblast development
      and function. In addition, there is evidence that the gp130 signal transduction
      pathway may be a critical site for the regulation of the rate of bone remodeling,
      and probably the coupling of bone resorption to bone formation. Sex steroids
      inhibit the expression of the genes encoding IL-6, gp80, and gp130, most likely
      by repressing the activity of transcription factors such as NF kappa B and NF-IL
      6. Considering this and the evidence that IL-6 autoregulates its own production
      and can upregulate the components of its receptor, removal of the direct
      inhibitory effects of sex steroids on IL-6, gp80, and gp130 could unleash a self
      amplifying cascade of events responsible for increasing not only the production
      of IL-6, but also the responsiveness of osteoclast progenitors, osteoblast
      progenitors, and stromal/osteoblastic cells that support osteoclastogenesis, or
      combinations of these cells, to IL-6 type cytokines. Such a scenario could
      explain both the increased osteoclastogenesis and osteoblastogenesis that follows
      loss of gonadal function and thereby the effect of such loss on the rate of bone
      remodeling and skeletal homeostasis. Manipulation of the effects of IL-6 type
      cytokines, by selectively targeting to specific bone cell precursors, may allow
      means of altering the balance between bone resorption and formation in favor of
      the latter.

PMID- 9629253
TI  - Acute and subacute effects of endotoxin on hypothalamic gaseous neuromodulators.
AB  - Although two-way communication between the hypothalamus and the immune system in
      now well established, particularly for the hypothalamo-pituitary-adrenal axis,
      the role of the gaseous neurotransmitters nitric oxide (NO) and carbon monoxide
      (CO) is much less well understood in terms of hypothalamic function. These agents
      are an important part of the peripheral inflammatory response; and their
      synthetic enzymes, NO synthase (NOS) and heme oxygenase (HO), respectively, have
      been localized to the hypothalamic PVN and SON. The induced generation of both NO
      and CO leads to the suppression of CRH and vasopressin, the major stimulators of
      the HPA. Thus, the addition of hemin to hypothalamic explants is maximally active
      at 1 microM in attenuating the release of CRH and vasopressin, and this dose is
      also most effective in generating biliverdin and associated CO. CO generation is
      also able to stimulate cyclooxygenase to produce prostaglandin E2, an established
      intermediary in the cytokine-stimulated activation of the HPA. Finally, inducible
      NOS mRNA is specifically induced in the hypothalalmus in response to endotoxin,
      in parallel to interleukin-1. These data provide increasing evidence in favor of
      NO and CO as counterregulatory agents in the HPA response to immune activation.

PMID- 9629255
TI  - Pain modulatory actions of cytokines and prostaglandin E2 in the brain.
AB  - Proinflammatory cytokines such as IL-1, IL-6, and TNF alpha are known to enhance
      nociception at peripheral inflammatory tissues. These cytokines are also produced
      in the brain. We found that an intracerebroventricular injection of IL-1 beta
      only at nonpyrogenic doses in rats reduced the paw-withdrawal latency on a hot
      plate and enhanced the responses of the wide dynamic range neurons in the
      trigeminal nucleus caudalis to noxious stimuli. This hyperalgesia, as assessed by
      behavioral and neuronal responses, was blocked by pretreatment with IL-1 receptor
      antagonist (IL-1Ra), Na salicylate, or alpha melanocyte-stimulating hormone,
      indicating the involvement of IL-1 receptors and the synthesis of prostanoids. IL
      6 and TNF alpha at nonpyrogenic doses also induced hyperalgesia in a prostanoid
      dependent way. Furthermore, the preoptic area (POA) was most sensitive to IL-1
      beta (5-50 pg/kg) in the induction of behavioral hyperalgesia. The maximal
      response was obtained 30 min after injection of IL-1 beta at 20 pg/kg. On the
      other hand, an injection of IL-1 beta (20-50 pg/kg) into the ventromedial
      hypothalamus (VMH) prolonged the paw-withdrawal latency maximally 10 min after
      injection. This analgesia, as well as the intraPOA IL-1 beta-induced
      hyperalgesia, was completely blocked by IL-1Ra or Na salicylate. Our previous
      study has revealed that i.c.v. injection of PGE2 induces hyperalgesia through EP3
      receptors and analgesia through EP1 receptors by its central action. The results,
      taken together, suggest (1) that IL-1 beta at lower doses in the brain induces
      hyperalgesia through EP3 receptors in the POA and (2) that the higher doses of
      brain IL-1 beta produces analgesia through EP1 receptors, probably, in the VMH.

PMID- 9629254
TI  - Alterations in sympathetic noradrenergic innervation in lymphoid organs with age.
AB  - Previous work in our laboratories has shown a selective age-related loss of
      sympathetic noradrenergic (NA) nerves from the spleen and lymph nodes of rats. In
      contrast, NA nerve fiber density is dramatically increased in the thymus of aged
      mice and rats. We hypothesize that the diminished splenic NA innervation in old
      rats is due to cumulative oxidative metabolic autodestruction of NA nerve
      terminals by high concentrations of norepinephrine released during specific time
      periods of immunologic reactivity. These old animals show a loss of NK cell
      activity, diminished T-cell proliferation, and diminished cell-mediated immunity.
      To assess the plasticity of NA nerve fibers in the aged rat spleen, male Fischer
      344 rats at 24 months of age were treated for 2 months with daily injections of
      0.25 or 1.0 mg/kg/day of L-deprenyl, followed by a 10-day drug washout period.
      The L-deprenyl-treated rats showed a remarkable sprouting of NA nerves into the
      splenic white pulp, with regrowth into appropriate vascular and parenchymal
      compartments. Rats with enhanced NA nerve regrowth showed increased IL-2 and IFN
      gamma production and NK cell activity compared with vehicle injected or
      uninjected age-matched control rats. We proposed that L-deprenyl stimulates NA
      nerve regrowth into secondary lymphoid organs, which leads to partial recovery of
      measures of immunosenescence.

PMID- 9629256
TI  - Endocrine and vagal controls of sympathetically dependent neurogenic
      inflammation.
AB  - Recently the very significant role of the postganglionic sympathetic neuron
      (PGSN) terminal in the production of neurogenic inflammation has been
      appreciated. An important model of this sympathetically dependent inflammation is
      venular plasma extravasation (PE) and neutrophil attraction produced by local
      intra-articular injection of the potent inflammatory mediator bradykinin (BK).
      Sympathetic-dependent PE in the synovium has been proposed as a protective
      mechanism in arthritis. In a recent series of studies, a novel mechanism has been
      discovered by which activation of primary afferent nociceptors exerts a potent
      feedback inhibition of PGSN-dependent PE. Activation of nociceptive afferents was
      shown to be involved in this feedback system. Such a negative feedback control of
      the acute inflammatory response would have survival value; the inflammatory
      response, as initiated by a high degree of positive feedback, and the
      inflammatory process itself when persisting can result in significant tissue
      injury. If indeed HPA axis activity plays a significant physiological role in the
      modulation of neurogenic inflammation, then physiological processes that modulate
      the HPA axis would be expected to influence neurogenic inflammation. A dramatic
      effect of this kind has been demonstrated, in the rat, for vagal afferent
      activity. In the presence of subdiaphragmatic (or celiac branch) vagotomy, the
      potency of nociceptive afferent activity to inhibit sympathetically dependent, BK
      induced PE was increased by four orders of magnitude compared to vagus-intact
      animal. Hypoactivity or hyperactivity of these vagally mediated mechanisms could
      contribute to diseases characterized by either an inadequate or an exaggerated
      inflammatory response.

PMID- 9629257
TI  - The role of the vagus nerve in cytokine-to-brain communication.
AB  - Peripheral interleukin-1 beta (IL-beta) and inflammatory stimuli that induce the
      synthesis and release of IL-1 beta produce a variety of central nervous system
      responses. Most proposals designed to explain how peripheral IL-1 beta influences
      the CNS have focused on blood-borne routes of communication. We will review data
      that indicate that at least some of the CNS response to peripheral IL-1 beta are
      instead mediated by a neural route of communication between the periphery and the
      CNS. IL-1 beta activates afferent vagal fibers that terminate in the nucleus
      tractus solitarius, and communication via the vagus is responsible for much of
      the hyperalgesia, fever, anorexia, taste aversions, increased levels of plasma
      corticosteroid, and brain norepinephrine changes produced by intraperitoneal
      injections of IL-1 beta and LPS. Data extending this analysis to TNF-alpha and
      intravenous routes will be described.

PMID- 9629258
TI  - Alternative pathways of neural control of the immune process.
AB  - Less well established alternative neuromodulatory pathways are neuropeptide
      mediated axon reflexes of sensory neurons, gut immunotrafficing, gut transmucosal
      transport of endogenous bacterial toxin, and the direct secretion of
      immunoregulatory cytokines by the brain. TNF-alpha and IL-1ra enter peripheral
      blood after their intracerebroventricular (i.c.v.) injection. Closed head injury
      or stroke increases blood IL-6 and the acute phase response; neuroblastomas
      immunosuppress by secreting TGF-beta. The IL-6 that appears in the blood after
      i.c.v. IL-1 in the rat is partly derived by secretion from the brain into the
      superior sagital sinus (Romero et al.; 1996. Am. J. Physiol. 270: R518) and is
      not dependent on peripheral sympathetic activation. Central endothelium and
      choroid plexus are potential sources of sagital sinus IL-6. TNF-alpha, which
      appears in blood after i.c.v. LPS, but not IL-1 beta, is due largely to toxin
      leaving the brain compartment and activating peripheral immunoreactive tissues.
      Antigens and cytokine immunoregulators drain into cervical lymph. Changes in
      glial milieu induced by intrinsic neuronal activity could by secretion from brain
      to blood modulate peripheral immunoreactivity.

PMID- 9629260
TI  - Cellular and molecular aspects of thymic T-cell education in neuroendocrine self
      principles. Implications for autoimmunity.
AB  - Thymic epithelial and nurse cells from different species express a repertoire of
      neuroendocrine polypeptide precursors. This repertoire exerts a dual role in T
      lymphocyte selection according to their status either as cryptocrine signals or
      as neuroendocrine self-antigens of the peptide sequences that are processed from
      those precursors then presented to pre-T cells. Thymic neuroendocrine self
      antigens correspond to peptide sequences highly conserved throughout evolution of
      their family. Though thymic MHC class I molecules are involved in the processing
      of thymic neuroendocrine self-antigens, preliminary data show that their
      presentation to pre-T cells is not allelically restricted. Thymic T-cell
      education in neuroendocrine families also implies that the structure of a given
      family may be presented to pre-T cells. Our studies have evidenced the homology
      between thymic neuroendocrine-related self-antigens and dominant T-cell epitopes
      of peripheral neuroendocrine signals (neuroendocrine autoantigens). The
      biochemical difference between neuroendocrine autoantigens and homologous thymic
      self-antigens might explain the opposite immune responses evoked by those two
      types of antigens (activation and memory induction vs. tolerogenic effect).
      Altogether, these studies support the therapeutic use of thymic neuroendocrine
      self-antigens in reprogramming the immunological self-tolerance that is broken in
      autoimmune endocrine diseases like insulin-dependent diabetes type I. As recently
      stated by P. M. Allen in an important review, the fate of developing T
      lymphocytes in the thymus is influenced by the numerous types of peptidic
      interactions within the thymic cellular environment. To define the precise nature
      of thymic cells and naturally occurring biochemical peptide signals involved in
      positive and negative selection of immature T cells has become a prominent
      objective for the future research efforts in thymic physiology. This paper will
      try to show how thymic neuroendocrine-related peptides synthesized and processed
      within the thymic microenvironment indeed can play a role both in the development
      of the peripheral T-cell repertoire and in the death of randomly rearranged, self
      reactive T cells.

PMID- 9629259
TI  - A positive role for thymus-derived steroids in formation of the T-cell
      repertoire.
AB  - T cells undergo rigorous selection processes in the thymus that are necessary to
      prevent T cells with either autoreactive or nonfunctional T-cell receptors (TCRs)
      from entering the periphery. Although both positive and negative selection depend
      on TCR-mediated signals, the means by which a thymocyte interprets these signals
      to result in survival or death is not understood. Glucocorticoids are known to
      induce thymocyte apoptosis at high concentrations, but at lower concentrations
      glucocorticoids can antagonize TCR-mediated deletional signals and allow survival
      of thymocytes and T cell hybridomas. Interestingly, transgenic mice in which the
      expression of the glucocorticoid receptor has been downmodulated specifically in
      thymocytes have abnormal thymocyte differentiation, indicating that
      glucocorticoids play a significant role in T-cell development. Furthermore, we
      have demonstrated the presence of steroidogenic enzymes in the thymic epithelium
      and can show that, in vitro, these cells readily synthesize pregnenolone, the
      first product in the steroidogenic pathway, and deoxycorticosterone. Inhibition
      of local glucocorticoid biosynthesis in thymi from TCR transgenic mice during
      fetal thymic organ culture (FTOC) revealed significant alterations in the process
      of thymocyte selection. These data suggest that glucocorticoids do not simply
      suppress the immune system but rather are necessary for thymocyte survival and
      differentiation.

PMID- 9629262
TI  - Thymic endocrinology.
AB  - The thymus involutes relatively early in life; cellular immune deficiencies of
      aging correspond to decline in function of the hypothalamic-pituitary-endocrine
      axis. Recent studies point to important roles for the pituitary, the pineal, and
      the autonomic nervous system as well as the thyroid, gonads and adrenals in the
      thymus integrity and function. Thymic function at the local level requires
      complex cellular interactions among thymic stromal cells and developing
      thymocytes involving paracrine and autocrine mediators including interleukins
      (ILs) 1, 2, 6, 7, 8, colony-stimulating factors (CSFs), interferon-gamma,
      thymosin alpha 1, and zinc-thymulin. An important endocrine function of the
      thymus is to package zinc in zinc-thymulin for delivery to the periphery. Thymic
      involution has been treated with interleukins, thymic hormones, growth hormone,
      prolactin, melatonin, zinc, and others. Our work to reverse thymic involution in
      hydrocortisone-treated, aged mice with interleukins, thymosin alpha 1, and zinc
      will be reviewed. Recent efforts to treat successfully immune deficiency in aged
      and cancer-bearing humans will be presented.

PMID- 9629261
TI  - Regulation of inhibitory pathways of the interleukin-1 system.
AB  - The IL-1 system includes two agonists, converting enzymes, antagonists, and two
      receptors (R). New elements and functions in the system will be discussed,
      including (a) cloning of a new isoform of the receptor antagonist; (b) further
      analysis of the type II IL-1-binding molecule as a decoy R. The modulation of IL
      1R by chemotactic signals was recently investigated. It was found that
      chemoattractants cause rapid release of the type II decoy R from myelomonocytic
      cells with a t1/2 of 30 sec. Induction of decoy R release represents an early
      event in the multistep process of recruitment. It may serve to block the systemic
      action of IL-1 leaking from sites of inflammation, while preserving
      responsiveness in situ. We recently cloned the first long pentraxin, PTX3 (human
      and mouse, cDNA and genomic) as an IL-1-inducible gene. The structural and
      functional features of this molecule as well as initial evidence of involvement
      in human pathology will be discussed.

PMID- 9629263
TI  - Stress-induced enhancement of cell-mediated immunity.
AB  - We have demonstrated that acute stress induces a large-magnitude, rapid, and
      reversible redistribution of leukocytes from the blood to other compartments
      within the body. These changes in leukocyte distribution are mediated by adrenal
      stress hormones. Because the skin is one of the target organs of a stress-induced
      redistribution of leukocyes, we hypothesized that such a leukocyte redistribution
      could be one of the factors by which acute stress may enhance cutaneous immune
      function. This hypothesis was tested by examining the effects of acute stress on
      cutaneous delayed-type hypersensitivity (DTH). DTH reactions are antigen
      specific, cell-mediated immune responses that, depending on the antigen involved,
      mediate beneficial (resistance to viruses, bacteria, and fungi) or harmful
      (allergic dermatitis, autoimmunity) aspects of immune function. DTH was induced
      by challenging the pinnae of previously sensitized rats with 2,4-dinitro-1
      fluorobenzene (DNFB). Experiments showed that acute stress administered
      immediately before the introduction of an antigenic challenge significantly
      enhances a cutaneous DTH response. In contrast, chronic stress suppresses
      cutaneous DTH. These results demonstrate a bidirectional relationship between
      stress and immune function, such that acute stress enhances, while chronic stress
      suppresses, an important class of immune responses in vivo. They also suggest
      that stress-induced alterations in lymphocyte redeployment within the body may
      play an important role in mediating these bidirectional effects of stress on cell
      mediated immunity.

PMID- 9629264
TI  - Mechanisms of antiinflammatory action of the neuroimmunomodulatory peptide alpha
      MSH.
AB  - The antiinflammatory effects of alpha-melanocyte-stimulating hormone (alpha-MSH)
      molecules, specifically alpha-MSH(1-13) and its COOH-terminal tripeptide alpha
      MSH(11-13), are well established. The peptides have been effective in tests of
      all major models of inflammation, and more recent tests have been extended to
      include experimental inflammatory bowel disease, CNS ischemia/reperfusion injury,
      and bacterial endotoxin-induced inflammation within the brain. The broad
      effectiveness of alpha-MSH molecules in all major types of inflammation indicates
      that the peptides exert actions that are very basic to the inflammatory process.
      Three general mechanisms of antiinflammatory action of alpha-MSH molecules have
      been identified: inhibition of production of inflammatory mediators by, or
      inhibition of inflammatory actions of, peripheral host cells; inhibition of
      peripheral inflammation induced by actions on melanocortin receptors within the
      brain; inhibition of CNS inflammation by local action of the peptides. It appears
      that alpha-MSH molecules have multiple actions that modulate the primitive
      inflammatory response.

PMID- 9629265
TI  - Cutaneous immunomodulation and coordination of skin stress responses by alpha
      melanocyte-stimulating hormone.
AB  - The capacity of the skin immune system to mount various types of immune responses
      is largely dependent on their ability to release and respond to different signals
      provided by immunoregulatory mediators such as cytokines. There is recent
      evidence that neuropeptides such as alpha-melanocyte-stimulating hormone (alpha
      MSH), upon stimulation, are released by epidermal cells including keratinocytes,
      Langerhans cells, and melanocytes as well as immunocompetent cells. Moreover,
      alpha MSH recently has been recognized as a potent immunomodulating agent, which
      inhibits the production and activity of immunoregulatory and proinflammatory
      cytokines such as IL-1, IL-2, interferon-gamma, downregulates the expression of
      costimulatory molecules (B7) on antigen-presenting cells; and recently turned out
      to be a potent inducer of inhibitory mediators such as cytokine synthesis
      inhibitory factor interleukin-10. Recently, it also was discovered that monocytes
      among the five known melanocortin (MC) receptors only express MC-1, which is
      specific for alpha MSH. The expression of MC-1 on monocytes is upregulated by
      mitogens, endotoxins, and proinflammatory cytokines. There is also recent
      evidence for the in vivo relevance of the immunosuppressing capacity of alpha
      MSH. Accordingly, in animals alpha MSH has been shown to inhibit the induction of
      contact hypersensitivity reactions and to induce hapten-specific tolerance. These
      findings indicate that, in addition to the cytokine network, neurohormones within
      the cutaneous microenvironment are a crucial element for the induction,
      elicitation, and regulation of cutaneous immune and inflammatory responses.

PMID- 9629266
TI  - Melatonin rhythms in mice: role in autoimmune and lymphoproliferative diseases.
AB  - Production of melatonin (MLT) in the pineal gland (PG) of inbred mice such as
      C57BI/6J, BALB/c, and AKR strains is still a matter of debate. In a recent study
      we validated the presence of MLT in the PG of these inbred mice. We found a short
      term MLT peak in the middle of the dark period with a pattern that mirrors that
      found previously in the serum. In another study, based on the known
      immunoregulatory role of MLT, we investigated the role of the PG and MLT in
      autoimmune diabetes mellitus type I using, as an experimental model, female
      nonobese diabetic (NOD) mice. Mice were pinealectomized or treated chronically
      with MLT (injected subcutaneously or administered via drinking water). We found
      that neonatal pinealectomy accelerates the development of disease in female NOD
      mice, whereas exogenous MLT protects animals. This is in spite of the fact that
      MLT increased the production of insulin autoantibodies (IAA). We conclude that PG
      and MLT influence the development of autoimmune diabetes, although the mechanism
      of action needs further investigation.

PMID- 9629267
TI  - kappa-Opioid receptors in marrow stroma mediate the hematopoietic effects of
      melatonin-induced opioid cytokines.
AB  - Melatonin exerts colony-stimulating activity and rescues myeloid progenitors from
      apoptosis, induced either in vivo or in vitro by cancer chemotherapy compounds in
      tumor-bearing mice. These effects are mediated mainly by T-helper cell-derived
      opioid cytokines with an apparent molecular mass of 15 kDa and 67 kDa that are
      recognized both by anti-interleukin-4 and anti-dynorphin B antibodies. These
      putative new cytokines were named melatonin-induced-opioid (MIO). The most active
      and naltrexone-sensitive MIO was the smaller molecule, which was called MIO15 and
      found to act on an opioid-binding site present in adherent bone marrow cells.
      However, the hematopoietic action of MIO15 was dependent on the presence of
      colony-stimulating factors (CSF). To investigate this point, we studied the
      ability of melatonin to rescue granulocyte/macrophage colony-forming units (GM
      CFU) in the bone marrow of tumor-free animals treated with cancer
      chemotherapeutic compounds. We found that melatonin not only is unable to protect
      bone marrow GM-CFU unless the mice are transplanted with Lewis lung carcinoma
      (LLC), but also that melatonin seems to increase the myelotoxicity of
      cyclophosphamide in tumor-free mice. In both tumor-bearing or healthy mice, the
      effect of melatonin is negated by naltrexone, indicating the involvement of
      MIO15. Competition studies classified the target opioid-binding site as a kappa
      opioid receptor with low affinity in tumor-free mice and high affinity in LLC
      implanted mice. LLC is known to release CSF. Consistently, addition of CSF in the
      form of lung-conditioned medium (LCM) to adherent bone marrow cells increased the
      affinity of the kappa-opioid receptor. Addition of antigranulocyte/macrophage
      colony-stimulating factor (GM-CSF) mAbs neutralized the effect of LCM. In
      conclusion, the affinity state of the kappa-opioid receptors in stromal bone
      marrow cells seems to modulate the hematopoietic effect of melatonin and/or
      MIO15.

PMID- 9629268
TI  - Signaling through delta opioid receptors on murine splenic T cells and stably
      transfected Jurkat cells.
AB  - beta-Endorphin (beta-EP) and delta opioid receptor (DOR) agonists affect immune
      functions such as lymphocyte chemotaxis, proliferation, and cytokine production.
      Recent studies indicate that both neuronal DOR and novel G-protein-coupled
      receptors with high affinity for beta-EP and DOR agonists are expressed by
      mononuclear cells. In addition, proenkephalin A mRNA and enkephalin-related
      peptides are expressed by lymphocytes. These investigations were conducted to
      identify signal transduction pathways that mediate the effects of beta-EP and DOR
      agonists on T cells. Calcium mobilization was studied because it is central to T
      cell activation initiated by antigen presentation to the T-cell receptor (TCR).
      Using the calcium-sensitive dye Fluo-3 and flow cytofluorometry to determine the
      concentration of free intracellular calcium, physiological concentrations of beta
      EP were shown to enhance concanvalin. A (con A)-stimulated calcium mobilization
      by murine splenic T cells (p < 0.01). The DOR antagonist, naltrindole, inhibited
      this, whereas CTAP, a selective mu OR antagonist, was ineffective. In addition, N
      Ac-beta-EP and the mu OR agonist DAMGO, failed to mimic the effects of beta-EP.
      Although it was less potent than beta-EP, DADLE, a DOR agonist, also enhanced Con
      A-induced calcium mobilization (p < 0.01). A DOR-transfected human T-cell line
      (DOR-Jul.1) was developed to study signal transduction. Both DADLE and the
      selective DOR agonist, deltorphin, rapidly increased intracellular free calcium
      concentrations; ED50s were 10(-9) M. Pertussis toxin prevented the response, and
      EGTA significantly reduced it. In addition, DADLE inhibited forskolin-stimulated
      cAMP production (ED50: 10(-11) M). These findings with normal splenic T cells and
      DOR-transfected T-cell line indicate that beta-EP and DOR agonists affect calcium
      mobilization. This is likely to modulate downstream pathways that regulate T-cell
      activation and function.

PMID- 9629269
TI  - KAT45 human pheochromocytoma cell line. A new model for the in vitro study of
      neuro-immuno-hormonal interactions.
AB  - Normal rodent adrenal chromaffin cells and the PC12 rat pheochromocytoma cell
      line produce IL-1 cytokines. The role, if any, of these cytokines is currently
      unknown. In PC12 cells, they induce the expression of the L-AA decarboxylase
      mRNA, a major step in the biosynthesis of catecholamines. Very little if any of
      these cytokines are detectable in normal human adrenal medulla, being confined
      mainly in the 17 alpha-hydroxylase-positive steroid cells of the zona
      reticularis. The aim of the present work was to find out if human
      pheochromocytomas produce IL-1 cytokines, in vitro, and to examine what local
      role they may exert. As a model, we have used the new KAT45 cell line, which
      emerged spontaneously from a primary human pheochromocytoma cell culture. We have
      found that the KAT45 cells secrete IL-1 beta at 47.8 +/- 9 pg/mg total cellular
      protein (n = 7, at 24 hours). IL-1 beta increased the concentration of
      norepinephrine in the KAT45 culture medium from 24.2 +/- 3.5 micrograms/mg
      protein (n = 6 controls, at 24 hours), to 33.2 +/- 3.5 (IL-1 beta 10 mg/ml) or to
      42.9 +/- 8 (IL-1 beta 30 mg/ml). This effect was blocked by IL-1ra. The KAT45
      cells also produce CRH and ACTH. IL-1 beta stimulated the secretion of CRH from
      19.2 +/- 4 pg/mg protein (n = 5 at 36 hours) to 38.7 +/- 4, an effect blocked by
      IL-1ra in excess. IL-1 beta had no effect on ACTH secretion.

PMID- 9629270
TI  - Mechanisms of hypothalamic-pituitary-adrenal axis stimulation by immune signals
      in the adult rat.
AB  - Immune stimulation increases the activity of the HPA axis, a phenomenon directly
      or indirectly mediated through cytokines. We have used two models, the peripheral
      administration of endotoxin (LPS) or turpentine-induced tissue injury to show
      that corticotropin-releasing factor (CRF) and vasopressin (VP), hypothalamic
      peptides released by cytokines, play a dominant role in the increased ACTH
      measured in these two paradigms. In turn, CRF and VP synthesis and/or release is
      modulated by catecholamines, prostaglandins (PGs), and nitric oxide (NO). These
      secretagogues are produced in the periphery and/or the central nervous system
      (CNS) in response to increased cytokine levels and act on CRF/VP neurons and
      nerve terminals. Finally, endotoxemia and local tissue inflammation may
      upregulate brain levels of tumor necrosis factor alpha, interleukin-1 beta,
      and/or interleukin-6, providing yet another mechanism through which the
      occurrence of systemic inflammation is conveyed to the brain. The relative
      importance of brain or peripheral intermediates appears to depend on the site at
      which cytokine levels are increased. We have shown, for example, that peripheral,
      but not brain, PGs are important in mediating the neuroendocrine influence of
      blood-borne cytokines, while PGs in the CNS play a role in situations
      characterized by elevated brain immune proteins. NO, on the other hand, restrains
      the response of the HPA axis to circulating, but not brain cytokines. These
      results illustrate the complexity of the mechanisms involved in the stimulation
      of the HPA axis and suggest that their specific involvement depends on the type,
      intensity, and duration of immune stimulation.

PMID- 9629271
TI  - Altered neuroimmunoendocrine communication during a condition of chronically
      increased brain corticotropin-releasing hormone drive.
AB  - Presently, it is clear that the brain, immune system, and endocrine system build
      a complex network of interactions at various levels. Inflammation, which may be
      regarded as a stressful challenge, initiates apart from immunological, autonomic,
      and neuroendocrine responses also profound behavioral (e.g., immobility, social
      disinterest) changes. Key mediators herein are corticotropin-releasing hormone
      (CRH) and cytokines, such as interleukin-1 beta (IL-1 beta). Currently, the
      behavioral changes, collectively termed sickness behavior, are thought to be
      adaptive responses to support the body's efforts to fight the infection. Using in
      vivo microdialysis and biotelemetry in freely moving animals, we have studied the
      monoaminergic circuits in the brain implicated in the regulation of physiological
      and behavioral responses to a peripheral inflammatory challenge (see also chapter
      of Linthorst and Reul in this volume). To expand our insight into the
      relationship between hypersecretion of CRH and physiological and behavioral
      abnormalities associated with stress-related disorders, a series of experiments
      was conducted with long-term centrally CRH-infused rats. These rats showed
      reduced body weight gain, decreased food intake, elevated plasma ACTH and
      corticosterone levels, thymus involution and immunosuppression, but,
      paradoxically, enhanced IL-1 beta mRNA expression in spleen macrophages. After a
      peripheral endotoxic challenge on the seventh day of treatment, the CRH-infused
      rats produced aberrant (i.e., blunted and/or delayed) HPA axis, fever,
      behavioral, and hippocampal serotonergic responses. However, endotoxin-induced
      plasma IL-1 and IL-6 bioactivities were significantly enhanced in these animals.
      The data show that chronically elevated central CRH levels as occurring during
      chronic stress result in defective central nervous system and immune system
      responses to an acute (inflammatory) challenge. These observations provide
      evidence that chronic CRH hypersecretion is an important factor in the etiology
      of stress-related disorders.

PMID- 9629272
TI  - A novel endogenous corticotropin release inhibiting factor.
AB  - ACTH is the major regulator of the body's adaptive response to stress and the
      physiological stimulus for glucocorticoid secretion. A hypothalamic corticotropin
      release inhibiting factor (CRIF) that inhibits ACTH synthesis and secretion has
      long been postulated but was not characterized until recently. We have recently
      identified a 22 amino acid peptide, prepro-thyrotropin releasing hormone (TRH)
      178-199 that inhibits basal and stimulated ACTH synthesis and secretion in vitro
      and stress-induced ACTH secretion in vivo. Prepro-TRH 178-199 is abundant in
      several brain regions, including the external zone of the median eminence, where
      its concentration changes in response to stress. We propose that this peptide is
      a physiological regulator of ACTH production: an endogenous CRIF. Because prepro
      TRH 178-199 is encoded within the same precursor as TRH, its expression is likely
      to be negatively regulated by thyroid hormones leading to changes in endogenous
      glucocorticoid levels. Streptococcal cell wall (SCW)-induced inflammation, a
      model of rheumatoid arthritis (RA), was alleviated after long-term thyroxine
      treatment. Inversely, a hypothyroid milieu led to decreased basal hypothalamic
      pituitary-adrenal activity, but increased expression of IL-1 beta and MIP-1
      alpha, specific markers for RA in humans. These results suggest that this
      putative CRIF may be an important component in the development of RA and that
      regulation of prepro TRH may be highly relevant to the development of other
      autoimmune diseases that are also exacerbated by low endogenous glucocorticoid
      levels.

PMID- 9629274
TI  - The hypothalamo-pituitary-adrenal axis of athymic Swiss nude mice. The
      implications of T lymphocytes in the ACTH release from immune cells.
AB  - Because of the well-known role of the thymus in the regulation of immune
      function, we investigated whether the lack of thymus may affect hypothalamo
      pituitary-adrenal (HPA) axis activity. Eight-week-old female Swiss nude (athymic)
      and BALB/c (normal) mice were used to study (a) the "in vivo" response of the HPA
      axis to various stresses and stimuli acting at either hypothalamic, pituitary, or
      adrenal levels and (b) the "in vitro" response of pituitary and adrenal cells to
      CRH and ACTH stimulation, respectively. The results indicate that (1) basal
      plasma ACTH levels were significantly (p < 0.05) higher in Swiss nude than in
      BALB/c mice, whereas basal corticosterone (B) levels were similar in both strains
      of mice; (2) the stress-induced release of ACTH and B in plasma was significantly
      (p < 0.05) lower in Swiss nude than in BALB/c mice, regardless of the stimulus
      applied; (3) the "in vitro" pituitary response to CRH and the adrenal response to
      ACTH were significantly (p < 0.05) lower in Swiss nude than in BALB/c mice; and
      (4) whereas hypothalamic CRH and pituitary ACTH contents were similar in both
      strains, adrenal B content was significantly (p < 0.05) lower in athymic mice.
      Immune reconstitution of the athymic nude mice by injecting splenocytes obtained
      from syngeneic heterozygous (i.e., immunologically fully competent) donors
      produced a significant increase in the B adrenal content of the nude mice. Among
      the splenocytes, CD4+ T-lymphocytes play a particularly important role in the
      release of ACTH from cells of the immune system. In conclusion, our results
      indicate that athymic nude mice have a blunted HPA axis response to various
      stresses and stimuli; this defect seems to reside at both the pituitary and
      adrenal levels. Immune reconstitution of the nude mice leads to a normalization
      of the adrenal B content.

PMID- 9629273
TI  - Neuroendocrine control of the thymus.
AB  - Thymocytes undergo a complex process of differentiation, largely dependent on
      interactions with the thymic microenvironment, a tridimensional cellular network
      formed by epithelial cells, macrophages, dendritic cells, and fibroblasts. One
      key cellular interaction involves the TCR-CD3 complex expressed by thymocytes
      with MHC-peptide complexes present on microenvironmental cells. Additionally,
      thymic epithelial cells (TEC) interact with thymocytes via soluble polypeptides
      such as thymic hormones and interleukins, as well as through extracellular matrix
      (ECM) ligands and receptors. Such types of heterotypic interactions are under
      neuroendocrine control. For example, thymic endocrine function, represented by
      thymulin production, is up-regulated, both in vivo and in vitro, by thyroid and
      pituitary hormones, including prolactin and growth hormone. We also showed that
      these peptides enhance the expression of ECM ligands and receptors, as well as
      the degree of TEC-thymocyte adhesion. In addition, we studied the thymic nurse
      cell complex, used herein as an in vitro model for ECM-mediated intrathymic T
      cell migration. We observed that T-cell migration is also hormonally regulated as
      ascertained by the thymocyte entrance into and exit from these lymphoepithelial
      complexes. Taken together these data clearly illustrate the concept that
      neuroendocrine circuits exert a pleiotropic control on thymus physiology. Lastly,
      the intrathymic production of classic hormones such as prolactin and growth
      hormone suggests that, in addition to endocrine circuits, paracrine and autocrine
      interactions mediated by these peptides and their respective receptors may exist
      in the thymus, thus influencing both lymphoid and microenvironmental compartments
      of the organ.

PMID- 9629275
TI  - Neuroimmunomodulation of aging. A program in the pineal gland.
AB  - We have investigated for 35 years the relationship between the neuroendocrine and
      the thymo-lymphatic, immune system. In the last decade we have shown that the
      pineal gland is a main adapter and fine synchronizer of environmental variables
      and endogenous messages into physiological modifications of basic functions. In
      particular the pineal gland itself seems to regulate, via circadian, night
      secretion of melatonin, all basic hormonal functions and also immunity. We have
      shown with several in vivo models that this fundamental role of the pineal gland
      decays during aging. Aging itself seems to be a strictly pineal-programmed event
      similar to growth and puberty. The continuation of our interventions with
      melatonin against the typical degenerative diseases of aging must be based on an
      accurate evaluation of its mechanisms of action. Melatonin being a ubiquitous
      molecule in nature, we suggest that it has acquired during evolution of the
      species numerous levels of activities. In fact, melatonin can be found in a large
      variety of cells and tissues, and bindings sites and "receptors" have been
      identified in many tissues and cells of the neuroendocrine and immune system.
      Therefore, the progressive understanding of the aging-programming role of the
      pineal gland also depends on studies of melatonin and its basic regulatory
      function. Our present studies will be described.

PMID- 9629276
TI  - Prolactin: a hormone at the crossroads of neuroimmunoendocrinology.
AB  - Prolactin (PRL), secreted by the pituitary, decidua, and lymphoid cells, has been
      shown to have a regulatory role in reproduction, immune function, and cell growth
      in mammals. The effects of PRL are mediated by a membrane-bound receptor that is
      a member of the superfamily of cytokine receptors. Formation of a trimer,
      consisting of one molecule of ligand and two molecules of receptor, appears to be
      a necessary prerequisite for biological activity. The function of these receptors
      is mediated, at least in part, by two families of signaling molecules: Janus
      tyrosine kinases (JAKs) and signal transducers and activators of transcription
      (STATs). To study these receptors, we have used two approaches: mutational
      analysis of their cytoplasmic domains coupled with functional tests and
      inactivation (knockout) of the receptor gene by homologous recombination in mice.
      We have produced mice by gene targeting in embryonic stem cells carrying a
      germline null mutation of the prolactin receptor gene. Heterozygous (+/-) females
      show almost complete failure to lactate, following their first, but not
      subsequent pregnancies. Homozygous (-/-) females are infertile as a result of
      multiple reproductive abnormalities, including ovulation of premiotic oocytes,
      reduced fertilization of oocytes, reduced preimplantation oocyte development,
      lack of embryo implantation, and the absence of pseudopregnancy. Half of the
      homozygous males are infertile or show reduced fertility. In view of the wide
      spread distribution of PRL receptors, other phenotypes including those on the
      immune system, are currently being evaluated in -/- animals. This study
      establishes the prolactin receptor as a key regulator of mammalian reproduction
      and provides the first total ablation model to further study the role of the
      prolactin receptor and its ligands.

PMID- 9629277
TI  - Growth hormone receptors and immunocompetent cells.
AB  - Growth hormone plays a significant role in regulation of the humoral and cellular
      immune responses in physiological as well as pathological situations. This role
      is exerted via the existence of specific receptors on cells of the immune system.
      Using flow cytofluorometry and biotinylated bovine GH, we have recently analyzed
      the expression of GH receptors (GHRs) in murine lymphoid organs. GHRs are widely
      expressed in all murine hematopoietic tissues and in fetuses, newborns, and 3-
      and 7-week-old animals. In the bone marrow, all hematopoietic lineages express
      variables levels of GH receptors, whereas in the thymus, this expression is
      mainly seen in CD4-, CD8-, CD4+CD8+, and CD8+ subpopulations. At the periphery,
      50% of splenocytes and peripheral blood lymphocytes and 20% of lymph node cells
      are GHR positive, with a wider receptor expression on B cells and macrophages
      (approximately 50%) than on T cells (approximately 20%), where the labeling is
      seen on both CD4+ and CD8+ cell subsets. Interestingly, the proportion of GHRs
      bearing CD4+ and CD8+ splenocytes is increased after T-cell activation with Con A
      or anti-CD3. Finally, all peripheral T cells expressing GHRs also express
      prolactin receptors. These data provide a molecular basis to study the factors
      controlling GHR expression and regulation of immune function.

PMID- 9629278
TI  - Insulin growth factor-I inhibits apoptosis in hematopoietic progenitor cells.
      Implications in thymic aging.
AB  - A decline in plasma concentrations of both growth hormone and IGF-I occurs during
      aging of humans and rodents, and this is accompanied by involution of the thymus
      gland. Exogenous growth hormone induces the synthesis of IGF-I, which acts on
      bone marrow-derived hematopoietic progenitors of the myeloid and lymphoid
      lineages to promote their replication and survival. The increase in survival of
      these cells is caused by the ability of IGF-I to inhibit their apoptotic death.
      In contrast to the multipotential colony-stimulating-factor IL-3, inhibition of
      apoptosis by IGF-I requires the activation of the critical intracellular effector
      PI 3-kinase. These data establish that hematopoietic progenitors can use more
      than one intracellular signaling pathway in order to maintain their survival. The
      data also extend the original hypothesis that IGF-I shares with the colony
      stimulating factors the properties of promoting DNA synthesis and inhibiting
      programmed cell death. Collectively, these data establish that hematopoietic
      progenitor cells are important targets for IGF-I, and this is likely to be
      important in understanding thymic aging.

PMID- 9629279
TI  - Cytokine expression and molecular mechanisms of their auto/paracrine regulation
      of anterior pituitary function and growth.
AB  - The pituitary gland expresses cytokines and their receptors. IL-2 receptor
      transcripts and protein products are co-localized in ACTH-, PRL-, and GH
      producing cells (double immunofluorescence). IL-2 and IL-6 (1-1000 IU/ml) are
      involved in the autocrine/paracrine regulation of normal and tumor (GH3
      mammosomatotroph cell line and adenoma cell cultures) anterior pituitary hormone
      producing cell growth (cell number, DNA synthesis, c-fos mRNA expression and
      autoradiography combined with hormone staining). IL-1 regulates the growth of
      normal pituitary cells but does not act on GH3 cells. IL-1ra, which blocks this
      action, is expressed in tumoral pituitary (mainly GH- and ACTH-) cells. In ACTH-
      cells, IL-1 enhances glucocorticoid feedback, stimulating glucocorticoid response
      element transcriptional activity. Cytokines, through specific functional
      receptors, act as inter/auto-cellular factors that regulate not only the function
      but also the growth of anterior pituitary cells.

PMID- 9629280
TI  - The substance P and somatostatin interferon-gamma immunoregulatory circuit.
AB  - Murine schistosomiasis mansoni is a parasitic disease in which flukes living in
      the portal vein of the host produce ova that deposit in the liver and intestines.
      In these organs, ova release antigens that induce chronic, focal granulomatous
      inflammation. IFN-gamma is an inflammatory cytokine important in macrophage
      activation and B-cell differentiation. A substance P (SP)/somatostatin (SOM)
      neurokine immunoregulatory circuit controls IFN-gamma production in schistosome
      granulomas. SP stimulates, while SOM inhibits IFN-gamma release, modulating IFN
      gamma-dependent circuitry. SP and SOM function through interaction with authentic
      SP and SOM receptors located on granuloma T cells. Also, the granulomas produce
      authentic SP and SOM14, as evidenced by the presence of mRNA and product. The
      granulomas have no nerves. This, and other data suggest that the inflammatory
      cells make these neurokines. Granuloma macrophages produce SOM. Macrophages from
      various sources express SOM mRNA in response to LPS, IFN-gamma, IL-10 or several
      other inflammatory mediators. Thus, the inflammation of murine schistosomiasis
      has a complete SP/SOM immunoregulatory circuit, which in turn is subject to
      immunoregulation.

PMID- 9629281
TI  - Selectivity of effects of vasoactive intestinal peptide on macrophages and
      lymphocytes in compartmental immune responses.
AB  - The major immunoregulatory effects of vasoactive intestinal peptide (VIP) are
      mediated by structurally distinct type I (VIPR1) and II (VIPR2) G protein
      associated receptors on many different types of immune cells. VIP is released in
      functionally relevant concentrations during many immunologic and inflammatory
      responses. Mast cells (VIPR1), macrophages (VIPR1 and VIPR2), B cells, and T
      cells (VIPR1, VIPR2, or VIPR1 and VIPR2) recognize and respond to VIP in patterns
      that are controlled by the relative levels of expression of VIPR1 and VIPR2.
      VIPR2 transduces human T-cell chemotaxis, expression of matrix metalloproteinases
      (MMPs) 2 and 9 and consequently basement membrane and connective tissue
      transmigration, while signaling suppression of proliferation and cytokine
      production. In contrast, VIPR1 fails to transduce T-cell chemotaxis but mediates
      suppression of chemotaxis and MMP expression elicited by some cytokines and
      chemokines. The relative representation of each type of VIPR, which is presumed
      to be under cytokine control, thus may determine T-cell responses to VIP and
      other immune mediators in tissue compartments innervated by VIPergic nerves.

PMID- 9629282
TI  - Selective regulation of T-cell development and function by calcitonin gene
      related peptide in thymus and spleen. An example of differential regional
      regulation of immunity by the neuroendocrine system.
AB  - In the course of our studies, we have shown the presence of calcitonin gene
      related peptide (CGRP) by immunocytochemistry in cell bodies and nerve fibers of
      the murine thymus and in a sparse innervation of the spleen. Receptors for CGRP
      have been characterized within these glands, and their activation by
      physiological levels of CGRP was found to suppress Con A-stimulated proliferation
      of thymocytes and splenic T cells as well as antigen-specific T-cell
      proliferation. This suppression is blocked by the antagonist for CGRP (CGRP 8
      37). Within the thymus cultures, the antagonist CGRP (8-37) alone enhanced
      proliferation of thymocytes during Con A stimulation, most likely by inhibiting
      the endogenous release of CGRP into the culture medium by resident thymocytes.
      Some of the CGRP-induced suppression of mitogenic stimulation of thymocytes, but
      not of splenocytes, was due to apoptosis. The antagonist, CGRP(8-37), did not
      block apoptosis caused by Con A or CGRP but rather enhanced it. Flow cytometric
      analysis of CGRP-treated cultures using antibodies to cluster determinates (CD)
      showed that the majority of thymocytes undergoing apoptosis induced by CGRP were
      of the CD4/CD8 double-positive type. These data indicate that apoptosis in the
      thymocytes is mediated by a CGRP receptor not sensitive to the antagonist CGRP(8
      37). Because proliferation of thymocytes and splenocytes induced by Con A is
      blocked by this antagonist and splenocytes are refractory to CGRP induced
      apoptosis, CGRP appears to mediate at least two separate functions on
      subpopulations of thymocytes and T cells via two different CGRP receptors within
      the gland. These effects of a neuropeptide exemplify the phenomenon of
      differential regional regulation of immunity by the autonomic and neuroendocrine
      systems.

PMID- 9629283
TI  - Levels of analysis in health science. A framework for integrating sociobehavioral
      and biomedical research.
AB  - One of the principal goals of the Office of Behavioral and Social Sciences
      Research at the National Institutes of Health is to facilitate interdisciplinary
      research between social, behavioral, and biomedical scientists. The purpose of
      this paper is to provide a framework for such interdisciplinary health research.
      The essence of this framework is the concept of levels of analysis in the health
      sciences. These levels include the social/environment, behavioral/psychological,
      organ systems, cellular, and molecular. The interdependence of these five levels
      of analysis suggests that advances in the health sciences may be accelerated by a
      more integrated, multilevel approach to research. The principles of integrated,
      multilevel research are outlined, and examples of research that support this
      approach are presented. Finally, some of the activities of the Office of
      Behavioral and Social Sciences Research that will further interdisciplinary
      research across levels of analysis are summarized.

PMID- 9629284
TI  - The role of cytokines in infection-related behavior.
AB  - Infections are associated with a specific behavioral pattern that includes
      hypomotility, hypophagia, increased sleep, decreased libido, and decreased
      exploration. This behavioral response is considered adaptive and important for
      the survival of the animal. A similar behavioral pattern was observed following
      treatment with endotoxin (lipopolysaccharide [LPS]) and cytokines, such as
      interleukin-1 (IL-1). Because the secretion of these cytokines is induced by LPS
      and infections, it is possible that they mediate the behavioral responses to
      infection. We have studied ingestive behavior and locomotor activity in mice
      following infection with influenza virus, or injection of LPS, IL-1, or IL-6. A
      lethal dose of influenza virus, LPS, IL-1a and IL-1b each decreased the intake of
      sweetened condensed milk and 24-hour food pellet intake and decreased locomotor
      activity. Mouse IL-6 was ineffective. A sublethal dose of influenza virus
      decreased food pellet intake and locomotor activity, but did not significantly
      alter milk intake. Indomethacin prevented the behavioral responses to IL-1, and
      attenuated those to LPS, but had only a very small effect on those to influenza
      virus. Similar results were obtained with the IL-1-receptor antagonist (IL-1ra);
      it completely prevented the responses to IL-1, attenuated those to LPS, but, even
      after chronic high dose administration, attenuated the effects of influenza virus
      infection only slightly. Our results suggest that while IL-1 may play an
      important role in the responses to infection, IL-6 does not. Moreover, IL-1
      cannot be the only factor contributing to the altered behavior of LPS-injected or
      influenza virus-infected mice.

PMID- 9629285
TI  - Cytokines and sickness behavior.
AB  - Peripheral and central injections of interleukin-1 (IL-1) and lipopolysaccharide
      (LPS) induce the expression of proinflammatory cytokines in the brain and have
      profound depressing effects on spontaneous and learned behaviors. These effects
      are mediated by vagal afferents, because they are abrogated by section of the
      vagus nerves at the subdiaphragmatic level in rats and mice. Vagotomy does not
      interfere with the synthesis and release of proinflammatory cytokines at the
      periphery, because plasma and tissue levels of interleukin-1 of vagotomized
      animals are similar to those of sham-operated animals. Furthermore, the
      consequences of vagotomy on the host behavioral response to peripheral cytokines
      are specific to the intraperitoneal route of administration of cytokines because
      vagotomized animals are still able to respond to IL-1 injected intravenously,
      subcutaneously, and into the lateral ventricle of the brain. Finally, substance P
      and cholecystokinin do not appear to play a key role in the transmission of the
      immune message to the brain because pretreatment by capsaicin or by specific
      antagonists of CCKA and CCKB receptors does not alter the behavioral effects of
      LPS and IL-1. All these findings point to the role of neural afferents for
      transmitting the immune message from the periphery to the brain.

PMID- 9629286
TI  - Neuroendocrine-immune disturbances in animal models with spontaneous autoimmune
      diseases.
AB  - According to our concept, the development of autoimmune disease depends on the
      presence of two sets of essential genes, one coding for an abnormal
      autoreactivity of the immune system, the other for a primary susceptibility of
      the target organ/structure for the immune attack. The final outcome of the
      disease in a given individual is then fine tuned by modulatory factors, such as
      diet or hormones. With regard to the latter, the immuno-endocrine interaction via
      the hypothalamo-pituitary-adrenal (HPA) axis has proven to be of special
      importance. Investigating the so-called Obese strain (OS) of chickens, an animal
      model with a spontaneously occurring Hashimoto-like autoimmune thyroiditis, we
      have first shown an impaired surge of glucocorticoid hormones after stimulation
      of the HPA axis by antigens or certain cytokines (glucocorticoid-increasing
      factors--GIFs). More recently, we have found a similar behavior in models with
      systemic autoimmune diseases, that is, murine lupus erythematosus and avian
      scleroderma. More detailed studies have, however, proven that the mechanisms
      underlying this altered immuno-endocrine communication via the HPA axis differs
      in different models. Finally, recent data point to the possibility that the
      classical pathways of glucocorticoid-T-cell interactions also take place in the
      thymus itself, which has been shown to be a site of steroid hormone production.

PMID- 9629287
TI  - Inflammatory disease as chronic stress.
AB  - It is now established that communication between the CNS and the immune system is
      bidirectional, that endocrine factors can alter immune function and that immune
      responses can alter both endocrine and CNS responses. In many respects CNS and
      endocrine responses to acute inflammation are similar to the changes associated
      with acute stress exposure. In contrast, during chronic inflammation associated
      with adjuvant induced arthritis (AA), although circulating levels of
      corticosterone are increased, the peptidergic regulation of the hypothalamus is
      different from that seen during acute stress. As the disease progresses, a
      paradoxical reduction occurs in CRH mRNA in the paraventricular nucleus (PVN),
      whereas PVN AVP mRNA increases. These data suggest that there is increased
      expression of AVP mRNA within the CRH cells of the PVN with an increased emphasis
      on AVP regulation of HPA output. Additionally, HPA function is altered during
      chronic inflammation such that responses to psychological stress (i.e. restraint)
      are significantly dampened, while responses to further inflammatory challenges
      are maintained. These data suggest that alterations in PVN peptide colocalization
      may be important in regulating the progression of peripheral inflammatory
      responses and that the effects of inflammation on the hypothalamus alter stress
      responsive systems. In addition to the AA model, we have similarly observed
      alterations in PVN peptide mRNA expression with disease onset in the murine MRL
      lpr/lpr and MRL +/+ model of SLE. Disease onset in murine SLE is spontaneous and
      does not rely on exogenous application of adjuvant; however, decreased levels of
      CRH in the PVN were observed from early disease onset in this animal model. It is
      suggested that alterations in CRH regulation in response to either acute or
      chronic inflammation may contribute as etiological factors to both psychiatric
      (i.e. neuropsychiatric SLE) and stress-related disease.

PMID- 9629288
TI  - Cytokines and fever.
AB  - Fever is induced in response to the entrance of pathogenic microorganisms into
      the body and is thought to be mediated by cytokines. Because these pathogens most
      commonly invade the body through its natural barriers and because body
      temperature is regulated centrally, these mediators are presumed to be produced
      peripherally and transported by the bloodstream to the brain, to act. It is
      generally considered that their febrigenic messages are further modulated there
      by prostaglandin E2 (PGE2). However, the detailed mechanism by which these
      cytokines signal the brain and activate the febrile response is not yet clear.
      Indeed, the specific role of each cytokine has been difficult to establish due to
      complex interactions among them. Furthermore, recent evidence suggests that
      different pyrogens may induce different cytokines; for example, i.v. LPS (a model
      of systemic bacterial infection) induces large increases in IL-6, but only small
      rises in IL-1 and TNF alpha plasma levels. Moreover, their appearance lags the
      fever onset. We recently found that subdiaphragmatic vagotomy, decomplementation,
      and blockade of Kupffer cells suppress the febrile response of guinea pigs to
      i.v. LPS, and that i.v. LPS rapidly stimulates the release of norepinephrine (NE)
      and, hence, of PGE2 in their preoptic-anterior hypothalamus (POA, the brain
      region containing the thermoregulatory controller). Based on these and other data
      in the literature, we hypothesize that LPS fever may be initiated as follows:
      i.v., LPS-->complement-->Kupffer cells-->cytokines?-->vagal afferents -->n.
      tractus solitarius?-->A1/A2 cell groups?-->ventral noradrenergic bundle? -->POA-
      >NE-->PGE2-->fever.

PMID- 9629290
TI  - Neuroimmune mechanisms of intestinal responses to stress. Role of corticotropin
      releasing factor and neurotensin.
AB  - Previous studies showed that exposure of experimental animals to immobilization
      stress increases colonic motility and that these effects are mediated by release
      of corticotropin-releasing factor (CRF), Studies from our laboratory showed that
      30-min immobilization stress of rats caused several not previously described
      colonic responses to stress, including increased colonic mucin and prostaglandin
      E2 (PGE2) secretion, increased colonic mucosal levels of cyclooxygenase-2 (COX-2)
      mRNA, and degranulation of colonic mast cells. These stress-associated colonic
      changes were reproduced by intravenous or intracerebral injection of CRF in
      conscious, nonstressed rats. Furthermore, pretreatment of rats with the CRF
      antagonist alpha-helical CRF9-41, hexamethonium, or the mast cell stabilizer
      lodoxamide inhibited our observed colon responses to immobilization stress. Our
      results indicate that CRF released during immobilization stress increases colonic
      transit via a neuronal pathway and stimulates colonic mucin release via
      activation of neurons and colonic mast cells. These results provide support for
      an important role for CRF in stress-mediated colonic responses and a link between
      the nervous and the immune systems.

PMID- 9629289
TI  - Interstitial cystitis: a neuroimmunoendocrine disorder.
AB  - Interstitial cystitis (IC) is a sterile bladder condition occurring primarily in
      females. It is characterized by frequency, nocturia, and suprapubic pain. IC
      symptoms are exacerbated during ovulation and under stress, thus implicating
      neurohormonal processes. The most prevalent theories to explain the
      pathophysiology of IC appear to be altered bladder lining and increased number of
      activated bladder mast cells. A defective bladder glycosaminoglycan (GAG) layer
      could allow penetration of allergic triggers, as well as chemicals, food
      preservatives, drugs, toxins, and adherent bacteria, all of which can activate
      bladder mast cells. Vasoactive, nociceptive, and proinflammatory molecules
      released can lead to immune cell infiltration and can sensitize neurons to
      secrete neurotransmitters or neuropeptides that can further activate mast cells.
      Mast cell-derived proteases can directly cause tissue damage, and it is
      noteworthy that urine tryptase is elevated in IC. Bladder mast cells are located
      close to neuronal processes, which are increased in IC, and they can be activated
      in situ by acetylcholine (ACh) and substance P (SP). Such activation is augmented
      by estradiol, which acquires significance in view of the fact that human bladder
      mast cells express estrogen receptors, but few progesterone receptors, which may
      explain the worsening of IC symptoms during ovulation. Finally, acute
      psychological stress in rats leads to mast cell activation that can be reduced by
      depletion of SP or neutralization of peripheral immune corticotropin-releasing
      hormone (CRH). These findings suggest that IC could be a syndrome with neural,
      immune, and endocrine components, in which activated mast cells play a central
      role.

PMID- 9629291
TI  - The influence of psychological stress on the immune response to vaccines.
AB  - We compared virus-specific antibody and T-cell responses to influenza virus
      vaccination in 32 caregivers of Alzheimer's disease (AD) patients and matched
      control subjects. Caregivers showed a poorer antibody response and virus-specific
      T-cell response following vaccination compared to the control subjects as
      measured by fourfold increases in antibody titers to the vaccine and lower levels
      of virus-induced IL-2 levels in vitro. We performed a second study in which forty
      eight medical students were inoculated with a series of three injections of the
      hepatitis-B (HEP-B) vaccine to coincide with the third day of three, three-day
      examination blocks. Twelve of the 48 medical students seroconverted after the
      first injection; these students were characterized by falling into the lower
      stressed/lower anxiety group of students. Students who reported greater social
      support and lower anxiety and stress demonstrated a higher antibody response to
      the vaccine and a more vigorous T-cell response to HEP-B surface antigen at the
      end of the third examination experience. The differences in antibody and T-cell
      responses to HEP-B and influenza virus vaccinations provide a demonstration of
      how stress may be able to alter both the cellular and humoral immune responses to
      vaccines and novel pathogens in both younger and older adults.

PMID- 9629292
TI  - Marital stress: immunologic, neuroendocrine, and autonomic correlates.
AB  - Ninety newlywed couples (mean age = 25), selected on the basis of extremely
      stringent mental and physical health criteria, were admitted to a hospital
      research unit for 24 hours to provide a detailed assessment of conflict
      resolution behaviors and changes in autonomic, endocrine, and immune function.
      Among these newlyweds, negative or hostile behaviors during marital conflict
      (coded from videotaped interactions) were associated with increased levels of
      epinephrine, norepinephrine, growth hormone, and ACTH as well as greater
      immunological change over the subsequent 24 hours. Wives demonstrated greater and
      more persistent physiological changes related to marital conflict than husbands.
      To assess the generalizability of these physiological changes, a similar
      laboratory paradigm was used with 31 older couples (mean age = 67) who had been
      married an average of 42 years. Consistent with the data from newlyweds, both
      endocrinological and immunological data showed significant relationships to
      negative behavior during marital conflict in these older couples. These findings
      suggest that abrasive marital interactions have important endocrinological and
      immunological correlates.

PMID- 9629293
TI  - Autonomic, neuroendocrine, and immune responses to psychological stress: the
      reactivity hypothesis.
AB  - We examined the effects of brief psychological stressors on cardiovascular,
      neuroendocrine, and cellular immune response in 22 older women to investigate the
      common effects of stress across systems. Results revealed that psychological
      stressors heightened cardiac sympathetic activation, elevated plasma
      catecholamine concentrations, and affected the cellular immune response (ps <
      0.05). In a replication and extension, 27 women caring for a spouse with a
      progressive dementia (high chronic stress) and 37 controls category matched for
      age and family income (low chronic stress) performed the 12-min laboratory
      stressor. Measures were taken before (low acute stress) and immediately following
      (high acute stress) exposure to the laboratory stressors as well as 30 min after
      termination of the stressor (recovery period). Acute stress again heightened
      cardiac sympathetic activation, elevated plasma catecholamine concentrations, and
      affected cellular immune responses (ps < 0.05), whereas chronic stress was
      associated with higher reports of negative affect, enhanced cardiac sympathetic
      activation, elevated blood pressure and plasma levels of ACTH, and diminished
      production of interleukin-1 beta (ps < 0.05). Correlational analyses in both
      studies further suggested that individuals who showed the greatest stress-related
      changes in HPA activation also exhibited the greatest diminution in cellular
      immune response.

PMID- 9629294
TI  - Effects of psychosocial treatment in prolonging cancer survival may be mediated
      by neuroimmune pathways.
AB  - Research has provided growing evidence of links between the social environment
      and cancer progression. Indeed, social support in the form of marriage, frequent
      daily contact with others, and the presence of a confidant may all have
      protective value against cancer progression. Furthermore, retrospective data
      suggest that major stressful life events are more prevalent in patients with
      relapse or malignancy, and thus may contribute to cancer morbidity. Initial
      studies of the effects of psychosocial intervention with cancer patients have
      provided some promising results. In three randomized prospective trials,
      protective effects of psychosocial interventions on cancer progression have been
      confirmed, while one matching and one randomized study showed no survival effect
      after psychosocial treatment. Though more research is clearly needed in this
      area, this body of evidence suggests that psychosocial factors have potentially
      powerful modulating effects on the course of disease. Here we review evidence of
      one possible mechanism whereby psychosocial factors may influence disease
      resistance capabilities: the neuroimmune connection. Suppressive effects of
      stress on immune function are well documented, and these effects have been shown
      to be modulated by social support. Thus, it is reasonable to hypothesize that
      supportive social relationships may buffer the effects of cancer-related stress
      on immunity, and thereby facilitate the recovery of immune mechanisms that may be
      important for cancer resistance. Data addressing this hypothesis are reviewed.

PMID- 9629295
TI  - Evidence for and pathophysiologic implications of hypothalamic-pituitary-adrenal
      axis dysregulation in fibromyalgia and chronic fatigue syndrome.
AB  - Chronic fatigue syndrome (CFS) is characterized by profound fatigue and an array
      of diffuse somatic symptoms. Our group has established that impaired activation
      of the hypothalamic-pituitary-adrenal (HPA) axis is an essential neuroendocrine
      feature of this condition. The relevance of this finding to the pathophysiology
      of CFS is supported by the observation that the onset and course of this illness
      is excerbated by physical and emotional stressors. It is also notable that this
      HPA dysregulation differs from that seen in melancholic depression, but shares
      features with other clinical syndromes (e.g., fibromyalgia). How the HPA axis
      dysfunction develops is unclear, though recent work suggests disturbances in
      serotonergic neurotransmission and alterations in the activity of AVP, an
      important co-secretagogue that, along with CRH, influences HPA axis function. In
      order to provide a more refined view of the nature of the HPA dusturbance in
      patients with CFS, we have studied the detailed, pulsatile characteristics of the
      HPA axis in a group of patients meeting the 1994 CDC case criteria for CFS.
      Results of that work are consistent with the view that patients with CFS have a
      reduction of HPA axis activity due, in part, to impaired central nervous system
      drive. These observations provide an important clue to the development of more
      effective treatment to this disabling condition.

PMID- 9629296
TI  - The reactivity of the cardiovascular system and immunomodulation by
      catecholamines in juvenile chronic arthritis.
AB  - Juvenile chronic arthritis is associated with clinical symptoms indicating that
      there is a dysregulation of the sympathetic nervous system (SNS). Our data show
      that patients with juvenile chronic arthritis have an altered function of the SNS
      associated with increased central noradrenergic outflow, presumably leading to
      increased vasoconstriction, resulting in a decreased response to an orthostatic
      stressor. We also investigated the consequences of the altered reactivity of SNS
      for the reactivity of the immune system to mediators of the sympathetic nervous
      system and to glucorticoids. It appeared that leukocytes of these patients have
      an altered response to catecholamines. Triggering of the beta 2-adrenergic
      receptor leads to reduced cAMP responses that are due to the higher rate of cAMP
      degradation. In addition, catecholamines induce the production of IL-6 by
      leukocytes of these patients, via triggering of alpha 1-adrenergic receptors.
      Healthy controls do not express functional alpha 1-adrenergic receptors.

PMID- 9629297
TI  - Neuroendocrine influences on experimental autoimmune encephalomyelitis.
AB  - Experimental autoimmune encephalomyelitis (EAE), a model for human multiple
      sclerosis, is an inflammatory disease of the CNS mediated by autoreactive T
      lymphocytes directed against the neuroantigen, myelin basic protein (MBP). EAE is
      inducible in the Lewis rat, which exhibits an acute monophasic disease, and in
      selected mouse strains, which show a remitting-relapsing or chronic course of
      paralysis. We examined the effects of neuroendocrine modulation by restraint
      stress on these models of EAE. In Lewis rats, daily cycles of restraint resulted
      in significant suppression of both clinical and histopathologic changes of EAE.
      Suppression of EAE was more pronounced in the female than in the male rat, which
      follows from the higher endogenous corticosterone levels in the female.
      Mechanistic studies suggested that stress affected the processing of MBP or the T
      cell idiotype. In the relapsing murine model of EAE, B10.PL mice were restrained
      beginning either before MBP challenge or after the establishment of relapsing
      disease. We observed a striking inhibition of EAE clinical signs in mice stressed
      before challenge relative to nonstressed controls. Interestingly, approximately
      10 days after termination of the stress period, clinical signs returned and were
      as severe or more severe than in control nonstressed animals. Stress administered
      after relapsing EAE was established had no protective effect. In vitro parameters
      revealed that only stress initiated before disease induction significantly
      reduced the frequency of MBP-specific lymphocytes in the spleen and lymph nodes.
      Both Th1 and Th2 cytokine responses were suppressed in stressed mice. T-cell
      receptor transgenic mice exposed to restraint showed a marked decreased in the
      number and functional activity of transgene-positive lymphocytes. In summary,
      elevated levels of endogenous neuroendocrine hormones exert a profoundly
      suppressive effect on both acute and chronic models of autoimmune CNS injury.

PMID- 9629298
TI  - Pathophysiologic and somatic investigations of hypothalamic-pituitary-adrenal
      axis activation in patients with depression.
AB  - Preclinical studies of inflammatory and autoimmune illnesses have demonstrated
      the importance of central components of the HPA axis in disease pathophysiology.
      The implications of these data for human illness are poorly understood. We have
      studied the pathophysiology of the hypercortisolism seen in two human illnesses
      involving the central nervous system, multiple sclerosis (MS) and depression, and
      looked for demonstrable somatic changes that may be associated with such
      hypercortisolism. Data from a study of medication-free patients with multiple
      sclerosis not in acute exacerbation suggest that compared with depression, MS is
      associated with increased prominence of hypothalamic vasopressin secretion (p <
      0.05). Data from studies of depressed patients with mild to moderate
      hypercorticolism (assessed by 24-hour urinary free cortisol excretion)
      demonstrate marked reductions in bone mineral density compared to healthy,
      carefully matched controls (p < 0.001), as well as changes in markers of bone
      metabolic activity similar to those seen in patients with Cushing's disease or
      exogenous glucocorticoid treatment (p < 0.05). Taken together, these studies
      suggest HPA axis dysregulations demonstrated in preclinical models of autoimmune
      and inflammatory illness also occur in human illness and may have important and
      lasting somatic sequelae.

PMID- 9629299
TI  - Neuroimmunomodulation in inflammatory bowel disease. How far from "bench" to
      "bedside"?
AB  - The chronic inflammatory bowel diseases (BID), Crohn's disease and ulcerative
      colitis, are characterized by recurrent periods of inflammation and tissue
      destruction. The clinical course is influenced by genetics, environmental
      factors, and the immune system. Recent insights (bench trials) benefiting from
      advances in genetic engineering and molecular biology have contributed to
      clinical care (bedside) in terms of actual or potential therapies. Does the
      neuroendocrine system significantly modify disease activity? Although
      conceptually appealing, evidence remains circumstantial. Compelling anecdotal
      reports exist that "stress" affects disease activity in terms of the frequency
      and severity of IBD flares (bedside), but the mechanisms underlying these
      observations are unknown. Evidence that neuroendocrine factors play a significant
      role in immunomodulation is progressing (bench). (i) Trinitrobenzene sulfonic
      acid (TNB)-induced colitis, although similar in unstressed Fisher and Lewis rats,
      shows marked worsening in stressed Lewis rats. (ii) Early studies of rectal pain
      perception suggest there are specific differences in neuroimaging studies (PET
      scans) in IBD patients compared to controls. (iii) Levels of substance P (SP) and
      its receptor are altered. (iv) Preliminary clinical studies with SP receptor
      antagonists show a trend toward improvement. (v) Importantly, the placebo
      response in clinical trials is as high as 45%. Evidence that neuroendocrine
      systems significantly modulate local inflammation is rapidly accumulating
      (bench), which will facilitate enhanced coordination of clinically relevant
      therapies (bedside).

PMID- 9629300
TI  - Mechanisms of glucocorticoid-resistant asthma.
AB  - The term "steroid- or glucocorticoid-resistant (GR) asthma" has been used to
      describe a group of asthmatics who demonstrate persistent airway obstruction and
      inflammation despite treatment with high doses of systemic glucocorticoids (GCs).
      There are at least two forms of GR asthma. The first group of patients has an
      acquired form of GC resistance. Analysis of their bronchoalveolar lavage (BAL)
      cells indicates an extremely high level of IL-2 and IL-4 gene expression as
      compared to BAL cells from GC-sensitive asthmatics. The incubation of T cells
      from normal individuals with the combination of IL-2 and IL-4 induces GC receptor
      binding defects, and concomitant GC receptor beta expression, in their cells.
      Similar abnormalities in GC receptor binding defects can be detected in freshly
      isolated cells from type 1 GR asthmatics, but this defect is reversible when
      their cells are cultured in the absence of IL-2 and IL-4. The second group
      involves patients with primary GC resistance who do not develop side effects on
      high-dose GCs and have very low numbers of GC receptors in their mononuclear
      cells. This defect is irreversible in culture and affects their T cells as well
      as non-T cells. The current studies provide new insights into mechanisms by which
      inflammation induces GC resistance and how defects in the GC receptor may
      contribute to chronic inflammation, creating the vicious cycle leading to chronic
      inflammatory diseases.

PMID- 9629301
TI  - Altered reactivity of the hypothalamus-pituitary-adrenal axis in patients with
      atopic dermatitis: pathologic factor or symptom?
AB  - Atopic dermatitis (AD) is a chronic inflammatory skin disease with the principal
      symptoms of dry skin, lichnification, eczematous inflammation, and an intense
      pruritus. Despite general acceptance that AD is a multifactorial skin disorder,
      dysregulation of immune functions (e.g., hypersecretion of immunoglobulin-E,
      altered cytokine profiles) is considered to be mainly involved in AD
      pathogenesis. Considerable evidence points to an immunoregulatory function for
      the hypothalamus-pituitary-adrenal (HPA) axis, suggesting that appropriate
      reactivity of the HPA axis is necessary to prevent the immune system from
      reaching a level that may be damaging for the host. It is further hypothesized
      that dysfunctional reactivity of the HPA axis may increase the vulnerability of
      the organism to immune-related disorders such as inflammatory diseases. In the
      present paper the role of the HPA axis for the development and chronification of
      allergic inflammation will be summarized and the potential pathological
      significance of a dysfunctional HPA axis in AD pathogenesis will be discussed.

PMID- 9629303
TI  - Effects of prolactin in stimulating disease activity in systemic lupus
      erythematosus.
AB  - Systemic lupus erythematosus (SLE), a chronic autoimmune illness, is influenced
      by hormones. High prolactin concentrations were associated with early death from
      autoimmune renal disease in NZB/NZW mice, an animal model of severe SLE. NZB/NZW
      mice that delivered and nursed pups and those that underwent pseudopregnancy had
      changes in serum IgG and autoantibodies. NZB/NZW mice treated with the prolactin
      suppressing drug bromocriptine had prolonged lives. Elevated serum prolactin
      concentrations are reported in SLE patients of both sexes. We found four women
      with long-standing hyper-prolactinemia who developed SLE. A survey of
      premenopausal women whose sera were submitted for autoantibody testing showed
      that 20% with anti-ds-DNA antibodies also had high prolactin levels. Many
      hyperprolactinemic patients whose sera were referred to an endocrinology
      laboratory had positive FANA tests (women 33%, men 53%) but did not have SLE.
      Disease activity was suppressed in six of seven SLE patients treated with
      bromocriptine. All had elevated disease activity and five became unexpectedly
      hyperprolactinemic after treatment stopped. Manipulating serum prolactin affords
      a means of treating clinical SLE activity.

PMID- 9629302
TI  - Interleukin-1 receptor defect in autoimmune NZB mouse brain.
AB  - Interleukin-1 receptors (IL-1R type I and II) have been characterized in murine
      nervous structures (hippocampus and frontal cortex), in vascular structures
      (vessels, choroid plexus), and in the anterior pituitary. Because interleukin-1
      (IL-1), injected or induced in the brain, is a powerful regulator of the stress
      axis and immune functions, it was of interest to investigate IL-1Rs and IL-1 in
      autoimmune mice. In control mice, bacterial lipopolysaccharide (LPS),
      administered i.p. or i.c.v., induces a sharp decrease in available brain IL-1
      receptors, in spite of a moderate increase in mRNAs for both receptor types. This
      is concomitant with an increase in IL-1 alpha, beta, and ra mRNA. Ligand
      production clearly overcomes receptor turnover. In autoimmune mice (NZB and
      NZB/NZW F1), a strong defect in IL-1R (type I) is demonstrated in the dentate
      gyrus. This tissue-specific defect cannot be explained by increased occupancy by
      endogeneous ligands as for LPS-treated mice. The transmission of the defect is
      Mendelian and suggests the involvement of a single gene. However patterns of IL
      1R mRNAs (evaluated by RT-PCR) are similar in NZB and in controls, suggesting a
      translational or post-translational abnormality. The contribution of this genetic
      disorder in the development of autoimmunity remains to be clarified. Because the
      brain IL-1 system sends inhibitory signals towards immune functions, this lack of
      functional IL-1 binding sites might participate in the disregulations observed in
      NZB autoimmune mice.

PMID- 9629304
TI  - Host resistance to mycobacteria is compromised by activation of the hypothalamic
      pituitary-adrenal axis.
AB  - Host resistance to the growth of Mycobacterium avium and Mycobacterium
      tuberculosis is controlled by a gene, termed Nramp1, that maps to chromosome 1 in
      mice. Activation of the HPA axis or treatment of macrophages from susceptible
      mice with corticosterone suppresses the expression of Nramp1 mRNA and results in
      an increased susceptibility to mycobacterial growth. In contrast, neither
      activation of the HPA axis nor treatment of macrophages from resistant mice with
      corticosterone results in an alteration in their resistance or suppression of
      Nramp1 expression. Investigation into the mechanism of the differential response
      of the macrophages to corticosterone indicated that differences were associated
      with the stability of the mRNA in macrophages from BCG-resistant mice. Thus,
      corticosterone induced the accelerated degradation of Nramp1 mRNA as well as mRNA
      of several other macrophage activation genes in macrophages from BCG-susceptible
      mice. Treatment of macrophages with corticosterone before the induction of Nramp1
      resulted in the accelerated degradation of mRNA in macrophages from both
      resistant and susceptible mice. The Nramp1 gene product appears to protect the
      mRNA of macrophage activation genes from degradation induced by corticosterone by
      an iron-dependent mechanism.

PMID- 9629305
TI  - Neurohormonal host defense in endotoxin shock.
AB  - Lipopolysaccharide (LPS) of gram-negative bacteria is capable of activating the
      immune system of higher animals, which may lead to cytokine-induced lethal shock
      and death. LPS has little toxicity for the frog and fish, but it kills the
      horseshoe crab instantly by causing intravascular blood coagulation. The response
      to LPS evolved from simple reactions in lower animals into an intense reaction in
      mammals that involves a massive immune activation leading to a profound
      neuroendocrine and metabolic response. This is now known as the acute-phase
      response (APR). During APR, LPS-binding proteins (LBP) are produced by the liver
      in rapidly increasing quantities under the influence of interleukin-6,
      glucocorticoids, and catecholamines. After combination with LPS, LPB is capable
      of activating monocyte-macrophages and granulocytes via the CD14 surface
      receptor. Other receptors (CD18, 80-kDa receptor) allow for direct action by LPS
      of phagocytes, B and T lymphocytes, and other cells. Numerous other acute-phase
      proteins are produced in the liver, including C-reactive protein, complement
      components, fibrinogen, enzyme inhibitors, and anti-inflammatory proteins.
      Similar responses may be stimulated by subtoxic doses of LPS or by detoxified
      LPS, which manifest in endotoxin tolerance. Tolerant animals and man show
      increased resistance to LPS, to infections, and to various noxious insults.
      Infection and various forms of tissue injury are also capable of causing APR.
      There is much evidence to indicate that APR, which manifests in febrile illness,
      is an efficient host defense reaction. It is an emergency response in cases where
      specific immunity fails to protect the host. Therefore, the neuroimmunoregulatory
      network converts the immune system to a less specific, but rapid and more
      efficient response, APR. The hypothesis is presented that intestinal LPS serves
      to amplify the APR in response to various insults, which contribute to host
      defense, regeneration, and healing.

PMID- 9629306
TI  - Stress-induced neuroendocrine modulation of viral pathogenesis and immunity.
AB  - Physical restraint (RST) was used to examine the interactions among the
      hypothalamic-pituitary-adrenal (HPA) axis, sympathetic nervous system, and the
      immune response to infection. In these studies, mice were infected with either
      herpes simplex virus (HSV) or influenza A/PR8 virus so that the impact of
      neuroendocrine activation could be assessed on disease pathophysiology and anti
      viral immunity. RST suppressed lymphadenopathy in draining lymph nodes, reduced
      mononuclear cellular infiltration in the lungs, and suppressed virus-specific
      cytokine and cytolytic T-cell responses. Blockade of type II glucocorticoid
      receptors (by RU486) restored cellularity and cytokine responses to both organs
      in restraint-stressed, infected mice. Thus, the HPA axis modulated cell
      trafficking and T-cell cytokine responses. However, RU486 treatment failed to
      restore cytolytic T-cell responses. Blockade of beta-adrenergic receptors (by
      nadolol), in combination with RU486 treatment, fully restored cytolytic T-cell
      responses, suggesting that catecholamines were involved in suppressing the virus
      specific CD8+ cytolytic T-cell response. RST also modulated the local development
      or expression of antibody-secreting cells (ASC) in the lungs draining lymph
      nodes, and spleen following infection of restrained mice. RST significantly
      suppressed the number of virus-specific ASC (IgM, IgG and subclasses IgG1 and
      IgG2a) in the lungs, mediastinal (MLN) lymph nodes and spleen, while it enhanced
      the responses in the superficial cervical (SCV) lymph nodes. This observation of
      differential modulation of ASC responses in the MLN and SCV lymph nodes supports
      the concept of tissue-specific immunoregulation in response to stress.

PMID- 9629307
TI  - Neuroendocrine dysfunction in African trypanosomiasis. The role of cytokines.
AB  - Sleeping sickness (SS; African trypanosomiasis) is an anthropozoonosis
      transmitted by the tsetse fly. Infection with Trypanosoma brucei in humans is
      associated with adynamia, lethargy, anorexia, and more specifically
      amenorrhea/infertility in women and loss of libido/impotence in men. Recent
      evidence suggests that experimental infection in animals with Trypanosoma brucei
      species causes polyglandular endocrine failure by local inflammation of the
      pituitary, thyroid, adrenal, and gonadal glands. In a cross-sectional study we
      investigated the prevalence and significance of neuroendocrine abnormalities in
      137 Ugandan patients with SS. In the untreated stage of the disease, there was a
      high prevalence of adrenal insufficiency (27%), hypothyroidism (50%) and
      hypogonadism (85%). Pituitary function tests suggested an unusual combined
      central (hypothalamic/pituitary) and peripheral defect in hormone secretion.
      Specific therapy resulted in a rapid recovery of adrenal/thyroid function,
      whereas hypogonadism persisted for years in a substantial portion of patients. We
      did not detect pituitary, thyroid, adrenal, and gonadal autoantibodies in
      patients with endocrine dysfunction, ruling out an autoimmune origin of the
      endocrine abnormalities. However, the presence of hypopituitarism correlated with
      high cytokine concentrations (TNF-alpha, IL-6) which--together with direct
      parasitic infiltration of the endocrine glands--are involved in the pathogenesis
      of SS-associated endocrine dysfunction.

PMID- 9629308
TI  - The encephalopathy associated with murine acquired immunodeficiency syndrome.
AB  - Mice infected with the LP-BM5 murine leukemia virus (MuLV) develop an immune
      deficiency syndrome together with an encephalopathy characterized by impairments
      in spatial learning and memory. These cognitive deficits are evident before the
      appearance of neuron loss and lymphoid cell invasion of the brain. Nonetheless, a
      prominent gliosis and a variety of neurochemical changes precede the development
      of cognitive deficits. The neurochemical abnormalities include significant
      decreases in striatal Met-enkephalin and substance P (but not somatostatin),
      increases in concentrations of quinolinic acid and platelet-activating factor,
      and alterations in brain fyn kinase. At this stage of the infection, some of
      these neurochemical changes can be reversed by glutamate receptor antagonists,
      cytokine inhibitors, and anti-retroviral agents. In later stages of the
      infection, however, the infected mice develop irreversible neuronal loss,
      invasion of hematopoietic cells, and increased viral burden in the CNS. In
      addition, motor-neuron dysfunction (hindlimb paralysis, weakness, and ataxia) and
      seizures are sometimes observed during the late stages of infection. Thus, the LP
      BM5 MuLV-infected mouse is a useful model for studying the chronology of
      neurodegenerative changes, ranging from reversible neuron dysfunction to
      irreversible neuron loss, that are associated with retrovirus-induced
      immunodeficiency.

PMID- 9629309
TI  - Glucocorticoid resistance and the immune function in the immunodeficiency
      syndrome.
AB  - Glucocorticoids, the final product of HPA axis, and their receptors (GRs) on
      mononuclear cells are crucial mediators in the endocrine-immune interaction. An
      alteration in GRs involving a lower receptor affinity (Kd) for glucocorticoids
      has been found in a group of advanced AIDS patients, who developed Addisonian
      symptoms (weakness, weight loss, hypotension, hyponatremia, and intense
      mucocutaneous melanosis) in spite of hypercortisolism and normal or slightly
      elevated values of ACTH (AIDS-GR). In these patients, data for the suppression
      test showed decreased cortisol and ACTH suppression in response to exogenous
      dexamethasone. The inhibitory effect of dexamethasone on radiolabeled-thymidine
      incorporation in mononuclear cells from these patients was also reduced.
      Monocytes of AIDS-GR patients had a receptor Kd of 10.5 +/- 4.2 nmol/l that was
      higher than that of other AIDS patients (AIDS-C) (2.9 +/- 0.8 nmol/l) and normal
      subjects (2.0 +/- 0.8 nmol/l: p < 0.01). Correlations were found between
      plasmatic IFN-alpha and receptor Kd on monocytes of AIDS-GR (r = 0.77). Poly (i)
      poly (c)-induced IFN-alpha production by monocytes was inhibited by
      glucocorticoids in the AIDS-C group and controls (approx. 80% in both groups):
      The effect was reversed by the receptor antagonist RU-486. By contrast,
      glucocorticoid did not inhibit IFN-alpha production in AIDS-GR group. In
      conclusion, levels of plasmatic IFN-alpha, a cytokine with antiviral properties,
      may be increased several times, and dexamethasone fails to inhibit monocytes' IFN
      alpha production only in AIDS with cortisol resistance, a disturbance that
      confirms an important immunoregulatory role of glucocorticoids in HIV disease.

PMID- 9629310
TI  - The neuropeptide alpha-MSH in HIV infection and other disorders in humans.
AB  - We measured plasma concentration of alpha-melanocyte-stimulating hormone (alpha
      MSH), a proopiomelanocortin derivative that modulates pyrogenic and
      proinflammatory effects of cytokines, in infectious and inflammatory disorders in
      humans to learn if changes in this peptide take place in naturally occurring
      disease. alpha-MSH was elevated in HIV-infected patients of the CDC groups III
      and IV. Although the peptide increased in the circulation of normal subjects
      injected with endotoxin, it was reduced in patients with septic syndrome. alpha
      MSH was found in the synovial fluid of arthritis patients, and its concentration
      was greater in the forms of arthritis marked by greater inflammation. We found
      that alpha-MSH is increased in the circulation of patients with acute myocardial
      infarction receiving thrombolytic therapy. Plasma concentrations of alpha-MSH is
      increased in the circulation of patients with acute myocardial infarction
      receiving thrombolytic therapy. Plasma concentrations of alpha-MSH were lower in
      healthy elderly subjects than in young controls. Because an excess of
      proinflammatory cytokines can have detrimental effects, we investigated the
      influences of alpha-MSH on the production of interleukin-1 (IL-1) and tumor
      necrosis factor (TNF) in HIV-infected patients and in patients with septic
      syndrome. Production of these cytokines in whole-blood samples stimulated with
      endotoxin was significantly reduced by treatment of blood with alpha-MSH. alpha
      MSH has been injected into at least 106 human subjects to study its effects on
      pituitary function, menstrual bleeding, and tanning. The peptide was always well
      tolerated. alpha-MSH administration could open new perspectives in treatment of
      inflammatory diseases in humans.

PMID- 9629311
TI  - Purification and characterization of a low-molecular-weight bovine kidney acid
      phosphatase.
AB  - A relative low molecular mass bovine kidney acid phosphatase was purified 1,640
      fold to homogeneity, with 7% recovery. The purified enzyme (specific activity 100
      mumol min-1 mg-1) was electrophoretically homogeneous with a relative molecular
      mass of 17.8 kDa, as determined by SDS-polyacrylamide gel electrophoresis. A
      broad pH optimum of 4.0-5.5 and a maximal enzyme activity at 60 degrees C were
      determined for the p-nitrophenyl phosphate hydrolysis. Apparent Km values of 0.14
      mM, 0.4 mM, 0.3 mM and 7.9 mM were obtained, at 37 degrees C and pH 5.0, for the
      best substrates p-nitrophenyl phosphate, beta-naphtyl-phosphate, flavin
      mononucleotide and tyrosine-phosphate, respectively. The enzyme activity was
      enhanced by guanosine but inhibited by ZnCl2 and CuSO4, p-cloromercuribenzoate
      and ammonium molybdate. Vanadate (Ki 0.47 microM), pyridoxal 5'-phosphate (Ki 2.2
      microM), inorganic phosphate (Ki 0.77 microM) are competitive inhibitors. Both
      glycerol and methanol increased significantly the acid phosphatase activity,
      acting as good phosphate acceptors in the transphosphorylation reaction.

PMID- 9629312
TI  - Carbonic anhydrase: a multigene-multifunctional enzyme.
AB  - Carbonic anhydrase is a zinc metalloenzyme that catalyzes the simple
      interconversion between carbon dioxide (CO2) and bicarbonate (HCO3-). Seven genes
      encode the CA isozymes in vertebrates. They are single chain peptides termed CAI
      VII. One CA isozyme is present in teleost fish. Three isozymes clearly appear
      together in birds. All seven types appear in mammals. Despite the great
      similarity among these isozymes, they present strong differences with respect to
      their kinetic properties. Many physiological and biochemical processes are
      related to the activity of CA isozymes.

PMID- 9629313
TI  - [Comparison between invasive tests for the diagnosis of Helicobacter pylori
      infections].
AB  - Helicobacter pylori is a Gram negative bacteria that colonizes gastric epithelial
      cells. It has been associated with several gastric disease including chronic
      gastritis and peptic ulcer. Helicobacter pylori infection diagnosis can be done
      with invasive and non-invasive methods. In invasive methods an endoscopic gastric
      mucosa biopsy specimen is used. In our study we compare the sensitivity,
      specificity, costs and applicability of four invasive diagnostic tests: culture,
      urease ultra-rapid test, histology (Giemsa and Hematoxilineosin stain) and
      fuchsin stained mucosal slides. Urease test was the easiest, fastest diagnostic
      test, with sensitivity of 86% and specificity of 100%, being also the cheapest
      test. We concluded that it should be the test of choice for Helicobacter pylori
      infection diagnosis.

PMID- 9629314
TI  - [Hepatic puncture biopsy in the outpatient clinic].
AB  - The authors present the results of a prospective study on percutaneous needle
      biopsy of the liver conducted at the Hepatology Outpatients' Ward of the
      Gastroenterology Unit of the University Hospital -" Universidade Federal de Juiz
      de Fora", MG, Brazil. In 16 months 61 biopsies were made in patients with chronic
      liver disease according to the technique described by menghini. The inclusion
      criteria were established by The Patient Care Committee of The American
      Gastroenterological Association. Abdominal ultrasound was done before and after
      the procedure. The patients stayed six hours under control (blood pressure and
      pulse rate) in the hospital. After 24 hours other clinical, laboratorial and
      ultrasonic control were performed. The main complication was local pain or in the
      right shoulder (32 patients--52.5%). Abdominal ultrasound after 24 hours revealed
      only one hematoma of the abdominal wall (1.8%). This study shows that the
      outpatient needle liver biopsy is a safe procedure with low complication rate
      when performed in a judicious way, by specialized personnel and under strict
      clinical control.

PMID- 9629315
TI  - [Cricopharyngeal dysfunction].
AB  - The idiopathic dysfunction of the cricopharyngeal muscle is a rare disease.
      Limited understanding of the pharyngoesophageal physiology and physiopathology
      make the management of this disease complex. We have studied three patients with
      idiopathic crycopharyngeal dysfunction submitted to cricomyotomy. One patient did
      not present improvement after surgery. The authors discuss the difficulties in
      making the diagnosis., the treatment and the selection of patients who will
      benefit from this surgical procedure.

PMID- 9629316
TI  - [Cholelithiasis in chronic Chageas' disease patients].
AB  - The studies on the occurrence of biliary lithiasis in patients with chronic
      Chagas' disease have shown conflicting results. Aiming at contributing to a
      better understanding of the topic was assessed, by ultrasonographic scan, the
      frequency of Colelithiasis in chagasic patients with different anatomo-clinical
      forms of the disease. A total of 128 patients were studied, 85 males (mean age:
      53 +/- 13 years) and 43 females (mean age: 53 +/_ 10 years) nineteen males and 18
      females had the cardiac form ; 32 males and 19 females the digestive form; 20
      males and 3 females the cardiac and digestive forms simultaneously; and 14 males
      and 3 females the indeterminate form. Controls were a series of 1139 individuals
      without Chagas' disease, 716 males and 423 females (mean age 46 +/_ 14 years for
      both sexes), who were submitted to postmortem examination. The frequency of
      cholelithiasis in chagasic males (14.1%) was significantly higher than in the
      controls (6%); by subgroup, it was significantly higher in the individuals with
      the cardiac and cardiac-digestive form (26.3% and 20% respectively), but not in
      those with the digestive form (9.4%). The frequency of colelithiasis was also
      significantly higher in chagasic females in the total (42%) and in the cardiac
      (50%) and digestive (31.6%) forms, when compared to the control group (14%). Male
      and female chronic chagasic patients have an increased frequency of
      colelithiasis, and therefore the preoccupation about this finding should not be
      restricted to the digestive form of the disease, as previous studies on this
      subject have suggested.

PMID- 9629317
TI  - Effect of tolerance to bacterial lipopolysaccharide on gastric emptying in rats.
AB  - This study examined whether pretreating rats with endotoxin (lipopolysaccharide,
      LPS) modifies the retardation of the gastric emptying of liquids induced by this
      same toxin. Male SPF Wistar rats (8-10 weeks old, 230-300 g) were divided into
      four groups of eight animals each that received either the vehicle solution
      sterile pyrogen free saline or LPS (50 mg/kg, intravenously), 96 and 5 hours
      before the measurement of gastric emptying. The four groups were defined on the
      basis of the sequence of intravenous injections namely saline + saline, saline +
      LPS, LPS + saline, and LPS + LPS. All the animals were fasted for 24 hours before
      and after the first injection and then received food ad libitum for the next 48
      hours, before being fasted again for 24 hours prior to the evaluation of gastric
      emptying. Throughout these periods, the rats had free access to water that was
      only withdrawn 1 h before the study. A saline solution containing red phenol was
      used as the test meal. Gastric retention (GR) was measured between 2 and 4 p.m.
      120 minutes after the orogastric administration of the meal. The results showed
      that in the saline + LPS group the GR (mean +/_ SEM = 61.1 +/_ 2.6%) was
      significantly greater (P < 0.05, Tukey test) than in relation to the saline +
      saline group (40.5 +/_ 2.6%). On the other hand, there were no significantly
      differences between the animals which received LPS + LPS (41.8 +/_ 2.5%) and
      those receiving LPS + saline (37.5 +/- 1.8%) or between these the groups and
      those receiving saline on both occasions. In conclusion the pretreatment with LPS
      suppressed the effect of endotoxin on gastric emptying by inducing early
      tolerance in the motor activity of the stomach in a manner similar to that
      described for other systems

PMID- 9629318
TI  - [Solid cystic tumor of the pancreas. Case report].
AB  - The solid and cystic tumour of the pancreas is a rare entity that occurs in young
      women. Clinically the patients are often asymptomatic, the tumor of variable size
      (2-10 cm) and show a fibrous encapsulation. In contrast to adenocarcinoma of
      pancreatic ductal cells, which is the most frequent tumor of the pancreas, this
      tumour have a slow growth, usually do not have metastases and have a favourable
      prognosis. The authors related the case and have done a revision of the illness.

PMID- 9629319
TI  - [Reversal of hepatorenal syndrome after liver transplantation. Considerations
      about 3 patients].
AB  - Hepatorenal syndrome was observed in 25% of the patients with end stage liver
      disease. In this situation they stayed longer time in intensive unit treatment,
      hemodialysis. This evolution was observed in 67% of them with this complication
      after surgery. In this report we describe three patients with hepatorenal
      syndrome reversible after liver transplant. We define the form of management of
      these patients after surgery, regard treatment with cyclosporine A, only 72 h
      after surgery, without administration of aminoglycosides and amphoterycin. This
      good evaluation also depends of absence of arterial hypotension or infection
      episodes during and after surgery. It also depends of the good conditions of the
      implanted liver.

PMID- 9629320
TI  - [Hepatic fascioliasis in children: uncommon clinical manifestations].
AB  - The present review has the objective to identify clinical epidemiologic
      characteristics and evolution for four children with Fasciola hepatica evaluated
      at the Pediatric Gastroenterology Unit at the Children's Health Institute, Lima,
      Peru, between 1988 and 1992. The first patient was a 9-year old girl who had
      fever, leg edema, collateral circulation and hepatomegaly, predominantly at the
      right lobe. The second was a 6-year old by who had upper gastrointestinal
      hemorrhage and fever; endoscopic diagnosis demonstrated hemobilia. The third case
      was a 12-year old boy who presented generalized edema. The fourth patient was a 9
      year old boy with jaundice, fever and upper gastrointestinal hemorrhage.
      Esophageal varices and cirrhosis were present. In the four patients the diagnosis
      was made by the identification of parasite eggs in the feces. The first three
      cases responded satisfactorily to treatment with bithionol; the fourth patient
      died because of systemic failure.

PMID- 9629321
TI  - [Evaluation of small intestine mucosal biopsies obtained simultaneously by
      suction capsule and endoscopic forceps in children with suspected enteropathy].
AB  - The aim of the study was to compare biopsy specimens obtained by suction with
      those obtained by endoscopy morphometrically and histologically in order to
      evaluate their adequacy for histological interpretation. For this, 23 children
      with suspected enteropathy underwent upper gastrointestinal endoscopy. For
      histological evaluation, biopsies were assessed for orientation, depth, length,
      presence of Brunner's glands and/or lymphoid follicles and presence of artifact.
      The mucosa total height and villi height were evaluated for morphometric
      assessment. The results of all the analysed parameters were not statistically
      significant, except for the presence of Brunner's glands that were most evident
      in endoscopic biopsies. Although, the suction capsule biopsies and the endoscopic
      ones were appropriate for histological interpretation in 91.3% respectively, the
      difference was not statistically significant. Based on the morphometric analysis,
      the mucosa total height and the villi height values in both biopsy techniques
      were not statistically significant different. The small intestine mucosal
      biopsies obtained by endoscopy compared with those obtained by suction capsule
      were adequate for histological interpretation.

PMID- 9629323
TI  - [Lactose intolerance in hospitalized infants with acute diarrhea due to classic
      enteropathogenic Escherichia coil (EPEC)].
AB  - Three hundred and eleven hospitalized weaned infants with acute diarrhea, all
      under 12 months of age, were studied in order to evaluate the development of
      lactose intolerance and its association with age, nutritional status, birth
      weight, dehydration and enteropathogenic agents identified in fecal samples.
      After been rehydrated the infants received whole cow' milk assuring the intake of
      100 kcal/kg per day. Lactose intolerance was defined according t the following
      criteria: 1) persistence of diarrhea associated with weight loss during 48 hours,
      2) development of vomiting and/or abdominal distention associated with excretion
      of carbohydrate in feces and/or acids tools, 3) metabolic acidosis associated
      with abdominal distention at anytime of refeeding period. Lactose intolerance was
      detected in 52.1% (162/311) of the patients and it was significantly associated
      with age under 6 months (P < 0.01), birth weight under 3000 grams (P < 0.01),
      development of dehydration (P < 0.01) and with enteropathogenic Escherichia coli
      (EPEC) serotypes infection (P < 0.01).

PMID- 9629322
TI  - [Study of serum antibody antigliadin of the immunoglobulin-A class in celiac
      disease].
AB  - Serum antigliadin IfA class antibodies (AAG-IgA) were measured by ELISA assay in
      65 children into three groups. Group I consisted of 20 control children; Group II
      of 31 celiac patients on different treatment periods (P1, on a normal diet; P2,
      after sixth month on gluten-free diet; P3, one three years of treatment and P4,
      three years and one month to nine years of treatment) and Group III of 14 food
      hypersensitivity patients. IgA-deficiency was ruled out in all patients.
      Positivity was considered for titers > 30.3 UA obtained from controls. The AAG
      IgA titer was positive in 9 of 10 celiac patients on P1. Nine of these 10
      patients were tested on P2; all cases showed a decrease in the AAG-IGA level and
      a significant difference was observed between the mean values for P1 and P2;
      although seven patients had maintained positive titers. On P3 and P4 all patients
      had AAG-IGa negative levels. On P1 the AAG-IGA liter levels were significantly
      higher than the values for P2, P3 and P4. The AAG-IgA values decreased towards
      control levels after one year of treatment. In Group III one out of 14 patients
      had a positive titer and the AAG-IgA values in this group were significantly
      lower than the celiac titers on P1 and P2 and no difference was found compared to
      patients titers on P3 and P4. The sensitivity of ELISA test was 90% and the
      specificity 93%. The AAG-IgA determination proved to be reliable for
      differentiating celiac disease from food hypersensitivity and useful in
      monitoring gluten-free diet compliance.

PMID- 9629324
TI  - Effects of misoprostol on pentylenetetrazol-induced seizures in mice.
AB  - The effects of prostaglandin E-analogue misoprostol on the susceptibility to
      pentilenetetrazol (PTZ)-induced seizures were examined in mice. Misoprostol (200
      800 micrograms/kg), given subcutaneously 45 min before the subconvulsive dose of
      PTZ (30 mg/kg, i.p) provoked dose-dependent clonic-tonic seizures (30 to 100%)
      and mortality in mice. At 300 g/kg, s.c., misoprostol pretreatment significantly
      (p < 0.05) lowered the onset latency to first convulsion as well as the latency
      to mortality induced by a convulsive dose of PTZ (60 mg/kg, i.p.). At this dose
      misoprostol was found to lower the CD50 and Ld50 values for PTZ by 21% and 36%
      respectively. The results suggest that prostaglandins are likely to lower the
      threshold for convulsions.

PMID- 9629325
TI  - Ultrastructure of cranial nerves of rats inoculated with rabies virus.
AB  - The V and VII cranial nerves of rats inoculated with rabies virus were studied by
      electron microscopy. The results were compared with the same cranial nerves of
      rats inoculated with rabies virus but vaccinated against the disease. The
      findings are those of axonal degeneration and intense demyelination of the nerves
      of the group of rats not vaccinated. The vaccinated rats showed some
      ultrastructural irrelevant alterations when compared with the other group. The
      degree of ultrastructural alterations found in the group of rats not vaccinated
      suggests that in rabies severe damage of the cranial nerves occurs and that this
      may be closely related to the clinical picture of the disease (hydrophobia).
      Furthermore, as far as the authors know, this has not been considered in the
      classic descriptions of rabies and it is possible that an immunologic process may
      take part in the demyelination observed in the present study.

PMID- 9629326
TI  - Morphological and quantitative study of the myenteric plexus of the ascending
      colon of rats subjected to proteic desnutrition.
AB  - We carried out this study with the purpose of contributing on the effects of the
      proteic desnutrition on the morphological aspects and quantitative analysis of
      the neurons in the myenteric plexus of the ascending colon of adult Rattus
      norvegicus. Twenty adult rats were divided into two groups: in one of them, we
      offered a normal ration with proteic level of 22% (control group) and in the
      other, a ration with a proteic level of 8% (experiment group) during 120 days. We
      did the whole-mount preparations for the ascending colon and stained them with
      the Giemsa technique and the histochemical technique of NADH-diaphorase. The rats
      with proteic desnutrition showed a body weight, on average, to be 35.1% less than
      those of the control group, and the colon was on average, 26.8% shorter and 6.7%
      narrower. Thus, it was to be expected that the colon of animals with proteic
      desnutrition had a neuronal density 31.62% greater than the rats of the control
      group. Nevertheless, the difference with the Giemsa technique was on average
      18.4%, demonstrating a mean neuronal loss of 13.25%.

PMID- 9629327
TI  - Morphological and quantitative analysis of the neurons of the myenteric plexus of
      the cecum of streptozotocin-induced diabetic rats.
AB  - The purpose of this work was to study the neurons of the myenteric plexus of the
      cecum of rats with chronic streptozotocin-induced diabetes. We used four
      experimental groups of animals. In groups D2 and D8 animals were killed two and
      eight months, respectively, after diabetes induction and groups C2 and C8 were
      used as controls. We carried out whole-mount preparations stained with Giemsa and
      NADH-diaphorase. We verified that the diabetes did not alter the shape and
      disposition of the myenteric ganglia; it provoked decrease on the neuronal
      density and increase on the incidence of weakly basophilic neurons. The effects
      of streptozotocin caused dilatation of the cecum still evidenced two months after
      induction, but no more observed on the eight months after induction. The smaller
      incidence of neurons in group D8 relative to group C8 was due to the early loss
      related to the drug toxicity and later to the aging in diabetic condition.

PMID- 9629328
TI  - [Autonomic neuropathy in patients with impaired glucose tolerance].
AB  - Impaired glucose tolerance (IGT) is a clinical situation characterized by mild
      hyperglycemia, which is estimated to afflict 7.8% of the Brazilian population.
      Diabetic neuropathy is the most common complication in diabetes mellitus and it
      is related to morbidity and lethality in this disease. The association between
      IGT and peripheral neuropathy is still a matter of great concern. PURPOSE AND
      METHOD: In order to determine if IGT is associated with autonomic neuropathy a
      cross-sectional study in 44 patients with impaired glucose tolerance test (Group
      1) was performed. The patients were compared to 43 control individuals (Group 2).
      Every patient in each group underwent anamnesis and standardized autonomic tests
      which consisted of heart frequency test, Valsalva maneuver, postural test and
      sinus arrhythmia. Routine hematologic exams as well as GTT were also made.
      RESULTS: Patients in group 1 had more systemic arterial hypertension, centripetal
      obesity, fasting and post-feeding hyperglycemia and dyslipidemia when compared
      with group 2. When we analysed the autonomic tests, the sinus arrhythmia test was
      abnormal in 54.5% of the patients in group 1 and in 32.5% in group 2 (p = 0.0039)
      and the Valsalva maneuver was abnormal in 34.1% of group 1 and in 7% of group 2
      (p = 0.004). The postural test was not different in both groups (p = 0.334).
      CONCLUSION: Our results show that the involvement of the autonomic nervous system
      was more frequent in patients with IGT when compared to controls. These findings
      can explain the increased lethality due to vasculopathies observed in this group
      of patients and also alert physicians to care for patients with impaired glucose
      tolerance test.

PMID- 9629330
TI  - Clusters of Bell's palsy.
AB  - The idiopathic facial paralysis or Bell's palsy installs abruptly or within a few
      hours, without any apparent cause. It corresponds to approximately 75% of all
      peripheral facial palsies. Three theories try to explain its pathogenecity:
      vascular-ischemic, viral and auto-immune. We reviewed the records of the EMG
      Sector, Hospital do Servidor Publico Estadual (Sao Paulo, Brazil), from 1985 to
      1995 and found 239 cases of Bell's palsy. Data were analysed according to age,
      gender, seasonal distribution of cases. There was a predominance of cases in the
      31-60 age bracket (40.59%). The female gender was responsible to 70.71% of cases.
      There was a predominance of cases in winter (31.38%) and autumn (30.13%), which
      was statistically significant. These findings let us to suppose that Bell's palsy
      predominates in females, in 41-60 years age bracket, and occurs predominantly in
      cold months. There are groups of clusters throughout temporal distribution of
      cases and cases are dependent on one each other or on factors affecting them all,
      which reinforces the infectious hypothesis (there is a rise in the incidence of
      viral upper respiratory tract infection during cold months).

PMID- 9629329
TI  - [Chronic inflammatory demyelinating polyradiculoneuropathy. Study of 18 cases].
AB  - This is a prospective study that describes 18 patients with chronic inflammatory
      demyelinating polyradiculoneuropathy (CIDP), idiopathic type. The patients have
      been followed for a period of 4 to 127 months. We evaluated the clinical
      characteristics, the evolution, and therapeutic response. Male patients
      outnumbered female patients in a proportion of 1.25:1. Symptoms first appeared at
      an age ranging from 6 to 85. Most of the patients denied the occurrence of
      preceding events and a progressive evolution prevailed over relapsing evolution.
      All patients had both motor and sensory dysfunction associated with loss of
      tendon reflexes, and only three patients (16.7%) had cranial nerve involvement.
      The cerebrospinal fluid protein levels were increased in 88.9% of the patients
      and mean level was 203.4 mg/dl. Electrophysiological studies revealed
      demyelination in all patients and axonal damage in 94.4%. Preponderant
      characteristics in the sural nerve biopsy of seven patients showed demyelination
      and remyelination, and changes indicative of axonal damage were often present.
      The anti-HLA Dr antibodies were found in the sural nerve of one patient and anti
      CD3 antibodies in the sural nerve of two. All patients were first treated with
      prednisone. The drug was maintained in reduced doses and given in alternate days
      to 72.2% of the patients with success. Two patients (11.1%) are asymptomatic even
      after the withdrawal of all medication. We administered azathioprine, associated
      or not with corticoid, to the four patients who had not had a satisfactory
      response to the prednisone treatment. By the time of the last evaluation 16
      patients (88.9%) had functional improvement.

PMID- 9629331
TI  - [Magnetic resonance in HTL-I associated myelopathy. Leukoencephalopathy and
      spinal cord atrophy].
AB  - Cerebral white matter lesions and spinal cord atrophy have been frequently
      reported in patients with HTLV-I associated myelopathy (HAM). The exact frequency
      and the clinical relevance of these findings still remain to be elucidated.
      Twenty-nine patients with HAM were studied by magnetic resonance imaging of the
      brain and spine. Cerebral white matter lesions equal or over 3 mm in diameter
      were considered abnormal. The spinal cord size was evaluated using an index we
      have called "spinal cord index". The radiological findings were correlated to the
      clinical features of the myelopathy. Cerebral white matter lesions occurred in
      52% of the patients, and spinal cord atrophy in 74%. There was no significant
      correlation between these abnormalities and the clinical features studied. These
      findings suggest that the resonance imaging is a useful method for detection of
      cerebral and spinal cord abnormalities in HAM patients. The absence of
      correlation between cerebral white matter lesions and either patient age or risk
      factors for cardiovascular disease suggests a possible association between the
      leukoencephalopathy and the infection.

PMID- 9629333
TI  - [Characteristics of epileptic seizures after ischemic stroke].
AB  - Cerebral infarctions are one of the most important causes of late onset epilepsy.
      We have studied 35 patients who presented epileptic seizures after ischemic
      stroke. All of them had the first seizure at least 24 hours after the stroke, and
      they had at least one recurrence of seizure. The objective was to determine the
      main characteristics of these seizures and to correlate them to clinical and
      laboratorial findings. The interval between the stroke and the first seizure was
      3 to 1650 days. Late onset seizures (> 14 days) were present in 89%, they
      occurred predominantly 6 to 12 months after stroke. Partial seizures (31/35) were
      more frequent than generalized ones. Status epilepticus occurred in only 3 cases.
      Most of the patients (30/35) had occasional seizures (< or = 1 seizure monthly).
      There were no association between seizure type and the time interval between the
      stroke and the first seizure, neither with the seizure frequency. The most
      frequent EEG finding was focal slowing of cerebral activity. Pharmacological
      control was easily obtained. No patient needed more than one drug for seizure
      control.

PMID- 9629332
TI  - [Fibrinogen as independent risk factor for ischemic stroke].
AB  - We have studied fibrinogen levels (Clauss technique) in atherothrombotic ischemic
      stroke patients, in order to determine its role as a thrombogenic risk factor.
      Twenty nine patients (20 men and 9 women) between 25 and 79 years old were
      studied; they all have had a atherothrombotic stroke. They were classified into
      two groups according to the result of their carotid doppler ultrasonography: gl
      without carotid flow reduction (n = 19) and g2-with carotid flow reduction (n =
      10). The fibrinogen mean value was 269 mg/dl in gl and 353 mg/dl in g2. There
      were 47% of patients in gl and 80% of patients in g2 who presented levels > 300
      mg/dl. The proportions of the groups were significantly different (p < 0.05).
      Considering the epidemiological value of 300 mg/dl, we conclude that the
      fibrinogen can be an independent risk factor for ischemic atherothrombotic
      stroke, specially in those whose carotid flow is reduced.

PMID- 9629334
TI  - Prognostic factors for recurrence of a first seizure during childhood.
AB  - This study was designed with the objective of evaluating the chance of recurrence
      in our area and to answer questions regarding prognostic factors capable of
      helping in the management of the first seizure in childhood. One hundred and
      thirty six children from 1 month to 12 years of age seen at the Pediatric
      Emergency Division of Hospital de Clinicas de Porto Alegre because of a first
      seizure with or without triggering factors were included in the study. The follow
      up included 121 children. We concluded that family history of seizures, presence
      of triggering factors at first event, seizure type, seizure duration and
      paroxysmal electroencephalographic abnormalities were predictive factors for
      seizure recurrence. The recurrence in this sample was 36.36% during the study.
      Cumulative recurrence risks were 14.88%, 23.14%, 28.93%, 33.06% and 35.54% to 3,
      6, 9, 12 and 15 months, respectively.

PMID- 9629335
TI  - Treatment of febrile seizures with intermittent clobazam.
AB  - Fifty children, 24 female and 26 male, with ages varying from 6 to 72 months
      (mean = 23.7 m.) that experienced at least one febrile seizure (FS) entered a
      prospective study of intermittent therapy with clobazam. Cases with severe
      neurological abnormalities, progressive neurological disease, afebrile seizures,
      symptomatic seizures of other nature, or seizures during a central nervous system
      infection were excluded. Seizures were of the simple type in 25 patients, complex
      in 20 and unclassified in 5. The mean follow-up period was 7.9 months (range = 1
      to 23 m.), and the age at the first seizure varied from 5 to 42 months (mean =
      16.8 m.). Clobazam was administered orally during the febrile episode according
      to the child's weight: up to 5 kg, 5 mg/day; from 5 to 10 kg, 10 mg/day; from 11
      to 15 kg, 15 mg/day, and over 15 kg, 20 mg/day. There were 219 febrile episodes,
      with temperature above 37.8 degrees C, in 40 children during the study period.
      Twelve children never received clobazam and 28 received the drug at least once.
      Drug efficacy was measured by comparing FS recurrence in the febrile episodes
      that were treated with clobazam with those in which only antipyretic measures
      were taken. Ten children (20%) experienced a FS during the study period. Of the
      171 febrile episodes treated with clobazam there were only 3 recurrences (1.7%),
      while of the 48 episodes treated only with antipyretic measures there were 11
      recurrences (22.9%), a difference highly significant (p < 0.0001). Adverse
      effects occurred in 10/28 patients (35.7%), consisting mainly in vomiting,
      somnolence and hyperactivity. Only one patient had recurrent vomiting which lead
      to drug interruption. These effects did not necessarily occurred in every
      instance the drug was administered, being present in one febrile episode and not
      in the others. We conclude that clonazepam is safe and efficacious in preventing
      FS recurrence. It may be an alternative to diazepam in the intermittent treatment
      of FS recurrence.

PMID- 9629336
TI  - [Continuous spike-wave activity during sleep. Electroencephalographic and
      clinical features].
AB  - Seventeen children were retrospectively evaluated. They exhibited continuous
      spike-wave activity during slow wave sleep (CSWS). Five of these had only speech
      problems and seizures (Landau-Kleffner syndrome) (group 1). The other cases had
      developmental milestones acquisition delay and/or mental retardation (group 2).
      Epileptic seizures were present in 11 of these, tetraparesis was observed in 5,
      hemiparesis in 2, microcephaly in 2 and behavior disturbances in 4 cases. The
      electroencephalogram showed in all cases diffuse CSWS. Group 1 showed diffuse
      activity, at times accentuated in the centrotemporal region (4/5). Group 2 had
      widespread discharges, including multifocal activity (5/12), sometimes with
      anterior predominance (7/12). We concluded that CSWS is a non specific
      electrographic pattern observed in some types of epilepsy in childhood that have
      different clinical presentation. It has however some topographic differentiation,
      depending upon the lesional sites.

PMID- 9629337
TI  - [Hypoxic-ischemic encephalopathy in newborn infants. Acute period and outcome].
AB  - Ninety four neonates with hypoxic ischemic encephalopathy HIE attended at the
      University of Ribeirao Preto since 1982 were studied in terms of the neurological
      alterations during the acute phase and outcome over a mean period of 47 months.
      From 43 newborns with HIE I, 40 recovered within 96 hours and 3 died. Among 40
      infants with HIE II, 37.5% recovered within the first week, and the others
      continued abnormal beyond the 7th day. All 11 infants with HIE III died before
      the second month of life. The HIE I group had no motor sequelae. Among the HIE II
      group, 34.5% showed cerebral palsy and 17.7% neuromotor retardation. 80.0% of
      those with sequelae persisted abnormal beyond 7th day of life, during the acute
      phase of the HIE. Epilepsy occurred in 17.5% of cases with HIE grade II, only
      among those with neuromotor sequelae. The IQ test did not show statistically
      significant difference between the HIE I, II without motor sequelae and the
      control groups. The authors reaffirm the value of the findings in the acute phase
      of HIE on the outcome of these patients.

PMID- 9629338
TI  - [Congenital muscular dystrophy and merosin deficiency].
AB  - Merosin alpha 2 chain, an extracellular matrix protein, is deficient in a
      proportion of patients with classical congenital muscular dystrophy (CMD). A
      study of clinical, laboratory and histopathological features of 18 patients with
      CMD was performed in relation to the merosin expression in muscle biopsy.
      Immunohistochemistry study showed that merosin was deficient in 11 patients and
      present in 7. None of the 9 merosin-deficient patients evaluated achieved
      walking. In contrast, 4 of 7 merosin-positive patients achieved independent
      ambulation. Creatine kinase levels were higher in merosin-deficient patients, but
      this difference was not statistically significant. Motor nerve conduction study
      was carried out on 12 children. All 4 merosin-positive patients had normal exams
      whereas 2 out 8 merosin-deficient patients presented decreased motor nerve
      conduction velocity. Among 69 histopathological features studied, we did not find
      any significant difference between merosin-deficient and merosin-positive
      patients. These results suggest that merosin status evaluation is important in
      the determination of the prognostic, since merosin-positive patients can achieve
      independent walking. This study also suggests that there is no relation between
      absence of merosin and histopathological features.

PMID- 9629339
TI  - [Electron microscopy study in neurodegenerative diseases in childhood].
AB  - Neurodegenerative diseases are a group of disorders in which there is storage of
      abnormal material in cells throughout the body due to an enzyme defect. The
      authors present the experience in the diagnosis of the neurodegenerative diseases
      in infancy by electron microscopical study of skin, conjunctival and rectum
      material of 89 patients and 2 necropsy cases. The age of the patients ranged from
      49 days to 13 years with speak age of incidence in first year of life (n = 28).
      Fifty patients were female and 39 were male. The most frequent sites of biopsy
      were the skin and conjunctival. Of the total 89 patients, 15 had a definitive
      diagnosis (16.8%) including 4 cases of gangliosidosis, 3 cases of
      mucopolysaccharidosis, a case of Gaucher's disease, a case of Niemann-Pick
      disease, 3 cases of neuronal ceroid lipofuscinosis and 3 cases of storage disease
      which could not be specified. The authors studied all these patients within
      clinic and ultrastructural aspects and concluded that electron microscopy is an
      important method in diagnosis of storage diseases but with a low sensitivity as a
      single "screening" test for patients with progressive encephalopathy.

PMID- 9629340
TI  - [Primary pediatric tumours of the central nervous system. Anatomopathological
      study of 623 cases].
AB  - Tumours of central nervous system (CNS) represent the second most frequent
      malignancy in children under 15 years of age but are the commonest cause of
      death. The authors present the epidemiologic and histopathologic analysis of 623
      primary tumours of CNS occurring during the period 1990 to 1996 in paediatric
      patients. In this period 3318 biopsies of CNS were analyzed. In this total were
      included 623 paediatric tumours (18 7%). The age of patients ranged from 5 months
      to 15 years, 325 tumours occurred in males and 298 in females. The majority
      affected the posterior fossa. The majority of paediatric neoplasias were of glial
      origin (n = 277). The most frequent tumours were: astrocytoma (27.9%),
      medulloblastoma (9.95%), craniopharyngioma (5.93%), ependymoma (4.97%) and
      glioblastoma (3.37%).

PMID- 9629341
TI  - [Intrathecal immunoglobulin synthesis evaluation in bone marrow transplantation].
AB  - The central nervous system involvement in chronic graft versus host disease
      (GVHD) has been suggested. Chronic GVHD resembles auto immune connective tissue
      disorders. In order to investigate the immunoglobulin intra blood brain barrier
      (BBB) synthesis during chronic GVHD, and contribute to understanding the
      pathophysiology of the disease, we studied 33 patients who underwent allogeneic
      bone marrow transplants (BMT) from HLA identical related donors. Immunoglobulin
      intra BBB synthesis was investigated quantitative and qualitatively. The samples
      were collected pre BMT, pos BMT and during chronic GVHD. There were no evidence
      of immunoglobulin intra BBB synthesis, and no oligoclonal bands were found. Only
      isolated cases suggested IgO and IgA intra BBB synthesis, and in one case IgM
      during GVHD.

PMID- 9629342
TI  - [Blood-brain barrier evaluation in bone marrow transplantation].
AB  - The blood-brain barrier (BBB) contributes to the central nervous system (CNS)
      immunological isolation. BBB has never been studied in patients who developed
      chronic graft-versus-host disease (GVHD) after allogeneic bone marrow transplants
      (BMT), from HLA identical related donors. BBB disruption was investigated through
      the cerebrospinal fluid (CSF) proteins, quantitative and graphically, in order to
      detect the incidence and possible pathophysiology of the CNS involvement in
      chronic GVHD. Thirty three CSF and matched serum samples from chronic myeloid
      leukemia patients were collected pre BMT pos BMT and during chronic GVHD. There
      was no evidence of BBB disruption in any patient studied.

PMID- 9629343
TI  - [Intra-adenomatous pituitary apoplexy].
AB  - The authors review the literature on intra-adenomatous pituitary apoplexy with
      special emphasis on pathophysiology, diagnosis and therapeutic approach. They
      present five cases, from a series of 86 patients with pituitary tumors, that
      developed this syndrome. The patients were diagnosed and followed by the
      Neurosurgery and Endocrinology Services of Hospital Universitario Clementino
      Fraga Filho, Universidade Federal do Rio de Janeiro. Diagnosis was confirmed by
      CT-Scan and MRI in all cases, and the treatment of choice was surgical.
      Conclusions point to the diagnostic difficulties and the urgency of treatment in
      this clinical setting.

PMID- 9629344
TI  - [Lipoma of the cerebellum. Case report].
AB  - Intracranial lipomas are rare. Usually they are incidental findings at autopsy.
      They occur in all the age groups and are often associated with hamartomatous
      lesions or neoplasms as cerebellum medulloblastomas. More frequently they are
      central and located at the midline. We report and discuss a case of lipoma of the
      cerebellum, an incidental finding at autopsy of a premature newborn.

PMID- 9629345
TI  - [Intraneural synovial cyst of the peroneal nerve. Case report].
AB  - The authors report the case of an intraneural synovial cyst of the peroneal
      nerve. The initial symptom was pain and weakness of dorsiflexion and eversion of
      the right foot. The patient was operated on and the cyst was totally resected.
      The authors discuss the pathogenesis, clinical diagnosis as well as the treatment
      of that uncommon lesion.

PMID- 9629346
TI  - [Persistent trigeminal artery associated with aneurysm of the middle cerebral
      artery. Case report and review of the literature].
AB  - The authors report a case of persistent primitive trigeminal artery
      angiographically demonstrated as an incidental finding. The persistent primitive
      trigeminal artery was associated with an aneurysm arising from the circle of
      Willis in the middle cerebral artery territory. The literature is reviewed and
      the embryology involved is related.

PMID- 9629347
TI  - Cervicogenic headache. Josey's cases revisited.
AB  - Before Sjaastad coined the term cervicogenic headache (CR) 15 years ago, neck
      related headaches have been considered by different authors for many years. Even
      after the publication of diagnostic criteria, dispute on the clinical picture,
      differential diagnosis, pathophysiology and treatment of CR still persists. A
      paper published in 1949 by Josey reports on 6 "illustrative" cases of cervical
      related headaches. Indeed, looked from a more recent perspective, those cases
      could eventually correspond to CH. Important topics such as the relatively high
      frequency, fixed unilaterality of the pain, relation to previous trauma,
      irradiation from the back to the forehead, normal or slightly abnormal
      roentgenograms, and the mechanical precipitation of attacks are some of the
      topics considered by Josey. The female gender was not prevalent in Josey's
      series. Traction and analgesics were basically the recommended treatment. CR is
      probably a common disorder, an idea already considered by a clinician in 1949.
      This syndrome was not adequately described before Sjaastad's group papers in the
      80's.

PMID- 9629348
TI  - Neurocysticercosos in South-Central America and the Indian subcontinent. A
      comparative evaluation.
AB  - Neurocysticercosis is an important public health problem in South-Central
      American and South Asia. A review of the differences in epidemiological and
      clinical attributes of cysticercosis and taeniasis in South Central America and
      India, respectively, is undertaken in the present communication. Intestinal
      taeniasis is hyperendemic in several American countries. In comparison, the
      prevalence of Taenia solium infestation is lower in India. The clinical
      manifestations in several American neurocysticercosis series comprise epilepsy,
      intracranial hypertension and meningeal-racemose cysticercosis, in roughly equal
      proportions. An overwhelming majority of the Indian subjects present with
      seizures. The commonest pathological substrate of the disorder in Indian patients
      is the solitary parenchymal degenerating cyst. The reasons for the predominance
      of solitary forms in India, and of multilesional forms in South Central America
      are discussed. The magnitude of Taenia solium infestation and the frequency of
      pork consumption in a given population appear to influence the quantum of cyst
      load in affected individuals.

PMID- 9629349
TI  - [Epidemiology of cerebrovascular disease in Joinville, Brazil. An institutional
      study].
AB  - The paucity of epidemiologic data, and the previous impression of high incidence
      of cerebrovascular disease in Brazil, made us elaborate a prospective
      institutional study in Joinville, Brazil, with objective of identifying first and
      recurrent episodes in stroke. This study occurred from March 1995 to March 1996.
      We evaluated during the first episode of stroke: incidence, mortality and
      fatality-case rate (in 30 days lethality), frequency of risk factor, time in
      hospital and distribution of cerebral infarcts by pathological subtypes. In this
      period, 429 patients with stroke were registered, 320 with the first episode. 98%
      of all the patients were submited to at least one computed tomography scanning.
      The episodes of cerebral infarcts were divided in pathological sub-types. Results
      showed that the annual incidence adjusted to the age of first stroke episode was
      156/100,000. The distribution by diagnosis was: 73.4% for cerebral infarct, 18.4%
      for cerebral hemorrhage and 7.5% for subarachnoid hemorrhage. The annual standard
      mortality rate was 25/100,000. The fatality case global rate in 30 days was 26%.
      Hypertension, previous stroke and diabetes were the most frequent risk factors.
      Only 25% of the patients were assisted within three hours of the onset of stroke.
      We concluded that the incidence rate of first episode of stroke is high in
      institutionalized patient in Joinville, Brazil. The mortality and fatality--case
      rates are similar to the ones of other populations.

PMID- 9629350
TI  - [Validation of a questionnaire for the diagnosis of headache in an outpatient
      clinic at a university hospital].
AB  - Headache is a common complaint with a high prevalence in ambulatory settings. The
      physical and neurological examinations are frequently normal. The use of
      questionnaires as a screening methods for patients with primary headache could
      facilitate the diagnosis in non-specialized medical centers. In the present
      study, we used a questionnaire, based on the IHS criteria and modified by the
      authors, applied to 204 patients from the outpatient clinic of the Hospital das
      Clinicas da Faculdade de Medicina da Universidade de Sao Paulo. Half of the
      patients were submitted to a clinical interview. We compared the results of the
      questionnaire with the results of the medical interview (gold standard). Most of
      the headaches we studied were primary headaches (89.6%). The questionnaire
      revealed a sensitivity of 90.2% and specificity of 57.9% for migraine detection
      with a chance corrected agreement (kappa) of 0.47 and a positive predictive (PPV)
      value of 65.7% and a negative predictive value (NPV) de 86.8%. The sensitivity
      for tension-type headache detection was 60.8% and the specificity 87.1% with a
      kappa value of 0.49 and a PPV of 77.8% and a NPV of 75.9%. We conclude that this
      questionnaire can be used as a screening method for diagnosing headache and that
      it can be applied by non-medical personnel. This questionnaire could also be used
      for population studies.

PMID- 9629351
TI  - [Pain, depression, and cultural concepts].
AB  - The influence of personal, cultural and affective factors and of the
      characteristics of the neoplastic diseases in the occurrence of pain and pain
      intensity in 92 patients presenting advanced cancer was evaluated. Pain usually
      moderate or severe during past week before the interview occurred in 62.0% of the
      patients. The duration of pain symptomatology lasted 10 months as an average.
      There was a higher proportion of patients with head and neck tumors in the group
      with pain than without pain. Cultural misconceptions about cancer pain control
      and the idea that doctors prescribe excessive amount of analgesics were
      correlated with higher intensities of pain (p < 0.05). Patients with pain
      presented higher depression scores than patient without pain (p < 0.05). Higher
      pain scores were correlated with higher depressive scores (p < 0.05).

PMID- 9629352
TI  - [Tremor: adaptation of a clinical scale].
AB  - The Fahn, Tolosa e Marin's clinical rating scale for tremor was adapted to our
      country for evaluation of tremor. This scale was applied to 123 patients with
      this movement disorder, selected from the Ambulatory of General Medicine at
      Hospital Universitario Pedro Ernesto da Universidade do Estado do Rio de Janeiro.
      These patients had been chosen no matter the etiology of their condition or their
      age. Although some variants may had influenced the scores of this particular
      scale, they did not seem to change its standardization and applicability.

PMID- 9629353
TI  - Somatotrophic and corticotrophic function outcome after transesphenoidal surgery
      in patients with sellar tumors and pre-operative endocrine deficits.
AB  - Sixteen patients with sellar tumors that were treated surgically and who had pre
      operative somatotrophic and corticotrophic function deficits were submitted to
      pre- and early post-operative insulin tolerance tests (ITTs). Seven patients had
      non-functioning adenomas, 5 had prolactinomas, 3 had craniopharyngioma and 1 had
      cordoma of the clivus. All patients had macro-tumors and none received
      radiotherapy within the studied period. Seven patients had GH, 4 had cortisol and
      5 had both GH/cortisol function pre-operative deficit. Five patients with
      isolated GH, 4 with isolated cortisol and 3 with both GH/cortisol deficiencies
      showed a postoperative functional recovery. New cortisol secretion deficits were
      observed in 2 patients postoperatively and both required long-term steroid
      replacement. These data suggest that preoperative endocrine deficits may be
      reversible after surgical decompression of the sellar region and that new
      endocrine deficits are rarely seen after surgery. All such patients should be
      tested postoperatively from an endocrinological point of view to reevaluate the
      need for replacement therapies.

PMID- 9629354
TI  - Acoustic neurinomas. Diagnosis and treatment.
AB  - We present our experience with 83 patients with acoustic neurinomas (January 1988
      to November 1996); 81 patients underwent surgery and 2 patients with
      intracanalicular neurinomas received conservative therapy due to their advanced
      age (1 case) and patient's option (1 case). The surgical approach was
      retrosigmoid/transmeatal and the goal was total removal in one procedure with
      preservation of facial and cochlear nerves. Radical removal of lesion was
      attempted in 79 cases and it was possible in 77 patients. Subtotal tumor
      resection was planned in 2 cases. Facial nerve function (grades I to III, House
      and Brackman) was preserved in 90% and hearing in 58% of those with preoperative
      hearing. Three patients died due to postoperative complications. Early diagnosis
      of acoustic neurinomas is the most important factor in the prognosis and is one
      of the most important conquest of neurophysiology and modern neuroimaging. The
      management of these patients still present many controversial points. This
      article presents the diagnostic procedures used for acoustic neurinomas, the
      advantages and disadvantages of the different surgical approaches and the
      alternative management of these lesions.

PMID- 9629355
TI  - Surgical treatment of premature sagittal synostosis.
AB  - A series of 50 consecutive children with premature sagittal synostosis is
      reported. All were treated surgically; 43 were male, 47 were leukodermic and two
      are siblings. In the pre-operative examination, the head shape, skull
      measurements and radiologic findings were evaluated; 38 children were operated on
      before six months of age and 12 of them, between six and 12 months of age. The
      surgical technique used was a wide biparietal craniectomy. Blood transfusions
      were occasional, being necessary for only six (12%) children. The children were
      admitted at the day of surgery and discharged between the second and third post
      operative day. No local or general complications were observed and no one died.
      The aesthetic result was considered good. The altered skull measurements before
      surgery reached normalization as far as the end of the first year after the
      treatment. It may be concluded that wide biparietal craniectomy is a procedure of
      great effectiveness in the treatment of the premature fusions of the sagittal
      suture.

PMID- 9629356
TI  - [Surgical treatment of cerebral vascular pathologies in epileptic patients].
AB  - Surgery of arteriovenous malformations (AVM) and of cavernous angiomas
      (cavernoma) in the majority of cases is indicated subsequently to episodes of
      bleeding. With the development of techniques for diagnosis and surgery for
      epilepsy of difficult control, indication for surgery of these vascular lesions
      has become greater. We present nine patients with cerebral vascular lesions and
      very frequent crises in spite of adequate clinical treatment. Ages ranged from 12
      to 42 years with an average of 25 years; there was a prevalence of the male sex
      (2:1). Surgery consisted of exercises of the lesion in all cases and in four
      there was also resection of the perilesional irritative area shown by
      electrocorticography. The pathologic study of lesions showed five cases of
      cavernoma, three cases of AVM, and one case of venous angioma. As to
      localization, we observed three lesions in the temporal lobe, four in the
      frontal, and two in the parietal region. Outpatient follow-up showed a reduction
      in crises in all of the patients, and seven evolved seizure free following
      surgery.

PMID- 9629357
TI  - [Subarachnoidal hemorrhage with cranial tomography without bleeding signals].
AB  - We observed 23 patients with clinical hypothesis of subarachnoidal hemorrhage
      (SAH) having cranial tomography (CT) without bleeding signals. The final
      diagnosis of SAH was made upon the cerebrospinal fluid (CSF) results. Twenty
      cases were submitted to brain angiography. They were focused under the clinical
      classification of Hunt & Hess. The main results were 1) 1/3 of patients had
      interval time between 24 and 48 hours after ictus and before CT and CSF making;
      this was the most sensitive CT time; 2) 55% of patients with brain angiography
      had aneurysm predominantly in the carotid and anterior cerebral artery territory;
      3) the dominant clinical degree was Hunt & Hess I e II. CONCLUSION: the results
      demonstrate the need of CSF test in case of SAH clinical diagnosis with CT
      showing no bleeding signals.

PMID- 9629359
TI  - Narcolepsy and depression.
AB  - Narcolepsy main symptoms include excessive daytime sleepiness and cataplexy. Its
      chronic course is accompanied by psychosocial impairment added to the
      difficulties and side effects of stimulants and tricyclics long term use.
      Depressive complaints are occasionally reported. The aim of this paper was to
      evaluate objectively the possibility of depression in a sample of 12 narcoleptics
      (7F; 5M), with mean age of 53 years (12 years SD), using the Beck Depression
      Inventory (BDI) and the Hamilton Rating Scale for Depression (HAM-D). The results
      showed absence of depressive disorder in 75.0% of the cases according to BDI (or
      58.3% according to HAM-D). The remaining patients had mild depression (only one
      patient presented major depression). The findings showed no correlation between
      narcolepsy and major depression.

PMID- 9629358
TI  - Fibrinolytic and factor XIII activity in subarachnoid hemorrhage.
AB  - The balance between fibrinolytic activity and coagulation mechanisms seems to
      play an important role in the rebleeding of a subarachnoid hemorrhage (SAH) due
      to aneurysmatic rupture. In the present paper we describe our findings in a group
      of patients (n 10) with SAH. The plasmatic levels of fibrinogen and their
      degradation products (FDP), APTT, prothrombin activity and factor XIII were
      determined within 72 hours of initial bleeding or of eventual rebleeding. Factor
      XIII activity in the first bleeding was 82.1 +/- 4%, while the levels of FDP were
      3.8 +/- 1 micrograms/ml. In patients presenting rebleeding (n 4), Factor XIII
      activity was 67.3 +/- 4.5% the day it manifested, which is significantly less
      than the values previously observed (p < 0.01), while the FDP level was 4.1 +/- 2
      micrograms/ml. The decrease of factor XIII activity suggests an important role as
      regards clot stability in rupture location. It is also possible to attribute a
      rebleeding predictive value to its activity reduction.

PMID- 9629360
TI  - The concept of nemesis in psychoneurosis.
AB  - A patient who has a nemesis fear as the basic process in his psychoneurosis feels
      that he is destined to repeat the life course of one of his parents to eventual
      long-term psychosis, or incapacitating physical illness or death by illness or
      accident. He feels that this will occur at about the same age as that at which
      his parent suffered his misfortune. The patient during his childhood and
      adolescence had a traumatic relationship with this parent, and is haunted by
      guilt feelings about it, and fears that avenging destiny, or nemesis, requires
      that he pay with a similar misfortune for that which he feels he caused. These
      patients improve much in psychotherapy, but the underlying nemesis fear, though
      much reduced in severity, is not entirely eliminated.

PMID- 9629361
TI  - [Meningiomas. Histopathological aspects and recurrence].
AB  - The authors assessed 246 cases of meningiomas that were classified as typical,
      atypical, anaplastic and papillary, according to previously defined criteria.
      Among the criteria used to define non-typical tumours, brain invasion was
      predominant in 62.3%. Meningiomas were typical in 75.22%, atypical in 19.1%,
      anaplastic in 5.68% of the cases. There was recurrence in 3.78% of typical,
      42.55% of atypical and 45.45% of anaplastic. The authors conclusion was that the
      criteria used to define typical and non-typical were adequate to predict a higher
      chance to tumour recurrences

PMID- 9629362
TI  - [Surgical anatomy of the nasal transphenoidal approach for pituitary tumors].
AB  - Different distances related to the nasal transphenoidal approach were measured on
      the hemiheads of eighteen cadavers in order to study its limits and advantages.
      The main mean measures obtained (mm) were: major diameter of the nostril 15.18:
      height of the nasal cavity 44.11, nostril-sella turcica distance 71.71. These
      results show that the nasal approach is wide and direct to the sella turcica. The
      present study demonstrate the possibility of preservation of the cartilaginous
      septum and other structures which are usually damaged when the sublabial approach
      is employed.

PMID- 9629363
TI  - Effects of epidermal growth factor on the [3H]-thymidine uptake in the SK-N-SH
      and SH-SY5Y human neuroblastoma cell lines.
AB  - The studies on the factors that regulate the biology of the neuroblastoma cell
      lines may offer important information on the development of tissues and organs
      that derive from the neural crest. In the present paper we study the action of
      epidermal growth factor (EGF) on two human neuroblastoma cell lines: SK-N-SH
      which is composed at least of two cellular phenotypes (neuroblastic and
      melanocytic/glial cells), and its pure neuroblastic subclone SH-SY5Y. The results
      show that EGF (10 ng/ml) significantly stimulates the incorporation of [3H]
      thymidine in the SK-N-SH cells only in the presence of fetal bovine serum (FBS)
      (control = 58,285 +/- 9327 cpm; EGF = 75,523 +/- 4457, p < 0.05). Such effect is
      not observed in the presence of a chemical defined medium, that is, in the
      absence of FBS (control = 100,997 +/- 4375; EGF = 95,268 +/- 4683; NS) In the SH
      SY5Y cells the EGF does not modify the incorporation of [3H]-thymidine either in
      the presence of 10% of BFS (control = 113,838 +/- 6978; EGF = 119,434 +/- 9441;
      NS) or in its absence (control = 46,197 +/- 3335; EGF = 44,472 +/- 3493; NS). The
      results here reported suggest that: a) EGF may affect the proliferation of cells
      derived from a primary human neuroblastoma; b) this is evident by the EGF-induced
      increase of [3H]-thymidine incorporation in SK-N-SH cells; c) it is required the
      presence of other growth factors, present in the FBS, for the mitogenic action to
      be accomplished; d) since the pure neuroblastic SH-SY5Y cell line are refractory
      to the EGF, the effects observed in SK-N-SH cells probably occur on the
      melanocytic/glial cell subpopulation.

PMID- 9629364
TI  - [Demyelination and remyelination after multiple intramedullary injections of
      ethidium bromide in Wistar rats].
AB  - The ethidium bromide model of demyelination has been employed to study the
      central nervous system response to several episodes of demyelination. Twenty
      seven Wistar rats received 2 to 4 intraspinal injections of 1 microliter of
      either 0.1% ethidium bromide in normal saline (19 rats) or saline 0.9% (8 rats)
      in different anatomical locations. The intervals between the injections ranged
      from 28 to 42 days. Ten days after the last injection all the rats were perfused
      with 2.5% glutaraldehyde. The spinal sections were evaluated macroscopically and
      by light and transmission electron microscopy. The lesions were typical of focal
      primary demyelination with preserved vascular structures and followed by
      remyelinization and varied in size and histological aspects. After multiple
      sequential ethidium bromide injections, the central nervous system seems to
      modify its response capacity to an inflammatory challenge although there is no
      change in its pattern of remyelination.

PMID- 9629365
TI  - Neuron number in the myenteric plexus of the ascending colon of rats. A
      comparative study using two staining techniques.
AB  - We carried out this study with the purpose of comparing the neuronal density in
      antimesocolic and intermediate regions of the colon of rats. We used the
      ascending colon of ten seven-months old Wistar rats. With the Giemsa method we
      found 29,046 neurons/cm2 on the antimesocolic region and 30,968 neurons/cm2 on
      the intermediate regions. With the NADH-diaphorase technique 12,308 neurons/cm2
      on the antimesocolic regions and 8798 neurons/cm2 on the intermediate regions
      were evidenced. The number of NADH-diaphorase positive neurons is significantly
      less than the number of Giemsa-stained neurons and that this difference is
      enhanced on the intermediate regions of the intestinal circumference. Therefore,
      to compare the number of neurons of an intestinal segment of a same species at
      the same age, it is necessary to take into consideration the technique employed
      and the region of the intestinal circumference from where the sample was
      obtained.

PMID- 9629366
TI  - [Extremely mild forms of multiple sclerosis with very long evolution].
AB  - The author presents the clinical history of three patients with a clinical
      picture of multiple sclerosis with a very long evolution and with a typical but
      mild symptomatology. In each case the diagnosis was corroborated by a MR
      imaginary. In the patient with a longer evolution the first symptoms, very
      smooth, appeared in 1943, when he was 19 years old, and the first clinical
      exploration was performed in 1945. We made the last control of this man in
      January, 1996. The other two patients were also controlled this same month. In
      conclusion, the author stressed the need of having always in mind the possibility
      of a "very benign" form of evolution of multiple sclerosis.

PMID- 9629367
TI  - [Progressive facial hemiatrophy (Parry-Romberg disease). Report of two cases
      associated with trigeminal neuralgia and cramps].
AB  - The authors report two cases of progressive facial hemiatrophy (PFH) associated
      with cranial nerves hyperexcitability. One of them (Case 1), a 41-year-old-woman
      noticed a slight atrophy on the left side of her face at age of ten. For the last
      three months, she has been suffering from fits of neuralgic pains on the left
      side of her face which have not ceased by drug treatment In view of this, a
      surgery procedure was planned for the patient. The other patient (Case 2), a 33
      year-old-woman has a 8 year history which started with cutaneous abnormalities
      (white and dark spots). Two years later she observed that her right cheek and
      right thigh had got a mild atrophy. Frequently, she has been complaining of
      cramps in the mandibular region which are precipitated, sometimes, by opening the
      mouth. A probable relation between neural excitability and PHF is discussed.

PMID- 9629368
TI  - [Secretory meningioma. Report of two cases].
AB  - Two surgically removed meningotheliomatous meningiomas with hyaline inclusions or
      pseudopsammoma bodies were studied. Both meningiomas showed expression of
      carcinoembryonic antigen and cytokeratin in the cells surrounding the hyaline
      bodies. There was widespread vimentin and epithelial membrane antigen except in
      the cells with hyaline inclusions. Clinically both had a severe cerebral edema.
      One of the cases showed multiple tumors, probably meningiomas. It is important
      not to misinterpret this variant of meningioma as metastatic neoplasm which may
      result in palliative treatment of a potentially curable tumor.

PMID- 9629369
TI  - [Dysembryoplastic neuroepithelial tumor. Case report].
AB  - Dysembryoplastic neuroepithelial tumor (DNT) is a relatively new neuroepithelial
      neoplasm that was first described by Daumas-Duport et al. in 1988. It was
      incorporated in the revised World Health Organization classification of brain
      tumors in 1993. The authors present the first case of DNT reported in the Latin
      American literature. A 16-year-old woman had been found at age of five years to
      have complex partial seizures accompanied by secondary generalization. She was
      treated with various anti-epileptic drugs but always with incomplete control of
      seizures activity. Neurological examination was normal. Magnetic resonance
      imaging demonstrated a lesion in the left temporal lobe. She underwent a
      craniotomy with complete resection of the tumor. Histological study showed
      atypical neuroglial proliferation characteristic of DNT. Monoclonal antibody
      immunostaining for glial fibrillary acidic protein and S-100 protein confirmed
      the glial component, and neuronal specific enolase and synaptophysin emphasized
      the neuronal component.

PMID- 9629370
TI  - "Gliomatosis cerebri" simulating an acute diffuse encephalomyelitis. Case report.
AB  - Neuroradiologic, neuropathologic and immunohistochemical features are reported in
      a young man with a impairment of the central nervous system mimicking an acute
      diffuse encephalomyelitis. A white male, 17 years old, healthy till 4 months
      before, when developed a right hemiparesis and after 2 months a bilateral
      hemiparesis with a progressive impairment of several cranial nerves. Magnetic
      resonance imaging showed multiple lesions without a mass effect that suggested
      myelin loss. He remained unconscious for almost one month before dying of
      pneumonia. The neuropathologic examination showed a heavy brain (1505 g) with
      herniations and a large right midbrain. There were several soft and pink areas
      mainly at the right midbrain, left cerebellum and in the white matter of the left
      cerebral hemisphere. The histopathologic sections showed diffuse blastomatous
      proliferation without total replacement or destruction of the original tissue.
      The tumor cells had astrocytic, oligodendrocytic and spongioblastic phenotypes,
      some of them with a GFAP-positive reactivity. There were focal anaplastic
      changes. The diagnosis of "gliomatosis cerebri" was only possible by the autopsy.

PMID- 9629371
TI  - Primary progressive freezing gait. Case report.
AB  - The clinical features of the primary progressive freezing gait, a rare and
      distinct neurological entity, have been described in some articles. This paper
      describes this gait disorder affecting one patient, whose condition's long course
      provoked no postural instability. As stated in the literature, the
      pathophysiology of the primary progressive freezing gait still remains unclear,
      although the lack of response to levodopa therapy suggests a possible involvement
      of nondopaminergic pathways. Alteration in the visual perception may be a
      potential cause for the condition.

PMID- 9629372
TI  - [Neurosurgical interventions and neuropsychological assessment. Case report].
AB  - The authors present the results from the neuropsychological examination of a boy
      suffering from refractory epilepsy due to a brain tumor. Cognitive deficits were
      subtle and were not disclosed during ordinary interview; there were few
      complaints also. Correlations between neuropsychological and neuroanatomical
      aspects are commented as well as the benefits from the neurosurgical
      intervention. The importance of neuropsychological testing in the setting of
      neurosurgical proceedings is emphasized.

PMID- 9629373
TI  - On the pathogenesis of headache following TIA.
AB  - Twelve out of 49 patients with single or multiple transient ischemic attacks
      (TIAs) had TIA-related headaches, mostly in close temporal relation to the
      ischemic onset. Headache predominated in patients taking vasodilators when TIA
      occurred or with orthostatic hypotension at the first clinical examination, but
      atrial hypertension or a personal history of migraine were not more frequent in
      patients with headache. The site of the pain did not correlate with the presumed
      territory of cerebral ischemia. Pain during TIA is conceivably due to an
      interaction between cerebral vessels and the surrounding nervous system. Blood
      vessels have a sturdy physiological role concerning blood flow regulation, with
      receptors and signaling molecules potentially involved with pain production.
      Reflex mechanisms should justify pain in other areas.

PMID- 9629374
TI  - The intracarotid amobarbital procedure (Wada test) with two protocols combined,
      Montreal and Seattle.
AB  - The intracarotid amobarbital procedure was carried out in 8 male and 7 female
      candidates to temporal lobectomy, and a female candidate to frontal lesionectomy,
      aged 18-50 (mean 32.5) years. Language and memory were tested after injection in
      each hemisphere. Both were measured by the Montreal procedure. In 9 patients
      language and memory were evaluated with the Seattle procedure too. In 12 patients
      the left hemisphere was dominant for language; three had bilateral dominance. In
      1 patient the Seattle procedure demonstrated the dominant hemisphere by
      relatively slowness of speech during the drug effect in the left hemisphere.
      Memory was defined to be in the left hemisphere in 12 patients, in the right in
      2, bilateral in 1 and in another lateralization was not possible. In 1 patient
      memory dominance was determined by the Montreal protocol alone because of lack of
      cooperation. These early results indicate that the methods may be complementary
      for determination of language and memory dominance in epilepsy surgery
      candidates.

PMID- 9629375
TI  - The predictive value of cerebrospinal fluid tap-test in normal pressure
      hydrocephalus.
AB  - Eighteen patients (mean age of 66.5 years) with normal pressure hydrocephalus
      (NPH) underwent a ventriculo-peritoneal shunt surgery. Prior to operation a
      cerebrospinal fluid tap-test (CSF-TT) was performed with measurements of gait
      pattern and psychometric functions (memory, visuo-motor speed and visuo
      constructive skills) before and after the removal of 50 ml CSF by lumbar puncture
      (LP). Fifteen patients improved and 3 were unchanged after surgery. Short
      duration of disease, gait disturbance preceding mental deterioration, wide
      temporal horns and small sulci on CT-scan were associated with good outcome after
      shunting. There was a good correlation between the results of CSF-TT and shunt
      surgery (chi 2 = 4.11, phi = 0.48, p < 0.05), with gait test showing highest
      correlation (r = 0.99, p = 0.01). In conclusion, this version of CSF-TT proved to
      be an effective test to predict improvement after shunting in patients with NPH.

PMID- 9629377
TI  - Alterations of cell-mediated immune response in children with febrile seizures.
AB  - The aim of the present investigation was to study the distribution of T-cell
      subsets in peripheral blood defined by monoclonal antibodies and by the
      lymphocyte proliferative response to phytohemagglutinin (PHA) in 30 children with
      febrile seizures and in 14 age-matched control subjects. Frequent respiratory,
      urinary and dermatologic infections were observed in 22 patients. The immunologic
      parameters showed that 64% of the patients presented an increased number of CD8+
      cells and a low helper/suppressor ratio was observed in 60% of the patients. In
      addition, the proliferative response of lymphocytes to PHA was impaired in the
      patients. It was observed the presence of inhibitory activity on lymphocyte
      function in the plasma of 33% of children with febrile seizures. These results
      suggest that patients with febrile seizures have an impairment of cellular
      immunity that may be connected with this epileptic syndrome and explain the
      infections observed.

PMID- 9629376
TI  - From the foot-mouth reflex to the hand-mouth reflex. A continuum of responses to
      appendicular compression.
AB  - We studied the mouth opening response to appendicular compression in two groups
      of children. This study was performed with the intention of testing the
      semiologic role of the act of mouth opening following stimulation of various
      regions, based on the hand mouth reflex of Babkin. Group I was formed by 33
      normal children who underwent monthly follow up assessments since birth; and
      group II consisted of 50 children older than 6 months of age, known to have a
      neurologic deficit and a neuro-psychomotor development equivalent to that of a
      child in the first trimester of life. We observed that the normal mouth opening
      response in group I was more pronounced following compression of the hand and
      forearm when compared to compression of the arm (p < 0.001). This response could
      persist for as long as the first 6 months of life. We were not able to elicit a
      mouth opening response following compression of the lower limb in this group.
      Among children from group II, we observed mouth opening responses to stimulation
      of all limb segments. Within the upper limb, the response was more pronounced
      following compression of the hand in comparison to the forearm (p < 0.01), and
      forearm in comparison to the proximal arm (p < 0.01). Stimulation of the foot was
      more effective in eliciting a mouth opening response when compared to equivalent
      stimulation of the lower leg (p < 0.05). However, there was no statistical
      difference when responses to stimulation of the lower leg and thigh were
      compared. The presence of the previously unreported foot-mouth response may serve
      as an indicator of central nervous system compromise and could be associated with
      a poorer prognosis. We believe that our observations of the specific foot-mouth
      response patterns may serve as a marker of early neuro-psychomotor development
      dysfunction during childhood.

PMID- 9629378
TI  - Clinical-neurologic, cytogenetic and molecular aspects of the Prader-Willi and
      Angelman syndromes.
AB  - The Prader-Willi syndrome (PWS) and the Angelman syndrome (AS) are human
      neurogenetic disorders involving the imprinting mechanism, at the 15q11-13
      chromosome region. The predominant genetic defects in PW are 15q11-13 deletions
      of paternal origin and maternal chromosome 15 uniparental disomy. In contrast,
      maternal deletions and paternal chromosome 15 uniparental disomy are associated
      with a different neurogenetic disorder, the AS. In both disorders, these
      mutations are associated with parent-of-origin specific methylation at several
      15q11-13 loci. We studied 5 patients suspect of PWS and 4 patients suspect of AS
      who were referred to the Medical Genetics Unit at the University Hospital of
      Medical School from Ribeirao Preto. Our objective was to establish the correct
      clinical and etiological diagnosis in these cases. We used conventional
      cytogenetics, methylation analysis with the probe KB17 (CpG island of the SNRPN
      gene) by Southern blotting after digestion with the Xba I and Not I restriction
      enzymes. We studied in patients and their parents the segregation of the (CA)***
      repeats polymorphisms by PCR, using the primers 196 and IR4-3R. All the patients
      had normal conventional cytogenetical analysis. We confirmed 3 cases of PWS: one
      by de novo deletion, one by maternal chromosome 15 uniparental disomy and one
      case with no defined cause determined by the used primers. We confirmed 2 cases
      of AS, caused by de novo deletion at the 15q11-13 region, and one case with
      normal molecular analysis but with strong clinical characteristics.

PMID- 9629379
TI  - Detection of metabolic disorders in high-risk patients. A pilot study in
      Salvador, Bahia.
AB  - The purpose of this pilot-study was to evaluate the applicability of a screening
      protocol for the detection of inborn errors of metabolism (IEM) in high-risk
      patients. The protocol was applied in 65 patients referred to the Medical
      Genetics Laboratory of the University Hospital Professor Edgard Santos due to the
      suspicion of an IEM. Eight of these patients (12.3%) displayed an abnormal result
      in the screening protocol. These patients, along with 22 who displayed normal
      results in the screening protocol but who presented clinical symptoms or signs
      suggestive of an IEM not detectable by the tests applied, were selected for a
      further diagnostic investigation. In 5 of these 30 patients (7.7% of the total
      sample) it was possible to establish the diagnosis of an specific IEM. The
      results indicate that the designed screening protocol was successfully applied,
      allowing the detection of affected patients in a frequency comparable to that
      observed in larger studies performed elsewhere. The continuation of this study
      and the enlargement of the sample will help to delineate the profile of IEM in
      northeast of Brazil and will allow the identification of a significative number
      of patients and families, who could benefit from the therapeutic and preventive
      measures available for these diseases.

PMID- 9629380
TI  - [Phasic activity of REM sleep in newborns and infants and its relationship with
      apnea episodes].
AB  - When the apnea hypothesis turned to be an explanation for sudden infant death
      syndrome (SIDS) many authors tried to find if near-miss or apparent life
      threatening events (ALTE) could be markers of SIDS. It was suggested that phasic
      REM activity is associated with increased respiratory neuron activity and
      prevents prolonged apnea in near-miss SIDS. In a previous retrospective study
      with newborns we did not confirm these results, nevertheless we had several
      babies with serious neurological disturbances. The aim of this study was to
      verify the relationship of phasic activity (rapid eyes movement and sucking
      bursts) with both apneic and non-apneic epochs during REM sleep. We studied 86
      children referred for evaluation because they presented an ALTE during sleep or
      apneas. The subjects were divided in three groups by age (newborns, n = 31; 1-6
      months, n = 48; and > 6 < 12 months, n = 7). They were all submitted to a
      clinical and neurological evaluation in order to detect possible etiological
      factors to the apneic episode. The polysomnograms (PS) consisted of EEG,
      submental EMG, electro-oculogram and cardiorespiratory monitoring. The records
      were made between 11 am and 15 pm for 2 or 3 hours. The electrodes were disposed
      in the 10-20 system. During one five-minutes epoch of REM sleep we verified the
      incidence of phasic activity (rapid eyes movement or sucking bursts) time locked
      to apneic episodes and compared with a similar duration non-apneic epoch. To
      evaluate the relationship of phasic activity with apneic and non-apneic eopchs we
      compared the incidence of rapid eyes movements and sucking bursts in each group.
      Our results showed that phasic activity of REM sleep (sucking bursts) seems to be
      more frequent in newborns in non-apneic epochs (p < 0.05). Between 1-6 months the
      number of rapid eyes movements were more frequent in non-apneic epochs (p =
      0.001). In conclusion our findings suggest that phasic activity of REM sleep
      seems to be more evident in nonapneic epochs during the first six months of life.
      Although central apneas may have their origin in an intrinsic disturb of the
      respiratory control center they may be influenced by the phasic activity of REM
      sleep. The rapid eyes movements and sucking bursts may have a protection effect
      against apneas at least in the first 6 months of life. which is the predominant
      period for SIDS. We suggest that the excitatory driving related to generation of
      phasic activity in REM sleep may block or atenuate tonic inhibition of
      respiratory motoneuron and avoid apnea. It is still open for discussion the
      possible relation between failure of this protective mechanism and SIDS.

PMID- 9629381
TI  - Epworth Sleepiness Scale outcome in 616 Brazilian medical students.
AB  - The Epworth Sleepiness Scale (ESS) measures daytime sleepiness in adults. This
      paper reports the following data in 616 medical students: 1-ESS scores, 2-its
      correlation with the declared night sleep time, 3-comparison with ESS values
      obtained from Australia, 4-comparison of ESS values in a sub-population of 111
      students tested early and late 1995. There were 387 males, 185 females and 4 not
      specified. Age = 20.16 +/- 2.23 (SD), ESS score = 10.00 +/- 3.69 (SD), declared
      sleep time = 7.04 +/- 1.03 (SD). ESS scores did not statistically correlate with
      sleep time. Average ESS score was statistically higher than in the Australian
      sample. Retesting of the medical students showed an increase in ESS values from
      March to November 1995. Sleep time difference was non-significant. Higher ESS
      scores in this sample seem to be related to shorter sleep time, but fatigue
      effects can not be ruled out.

PMID- 9629382
TI  - Cardiovascular autonomic tests in diabetic patients with gastroparesis.
AB  - The aim of this report was to study the cardiovascular autonomic tests in the
      evaluation of diabetic patients with gastroparesis. Forty diabetic subjects were
      divided into two groups: one group with gastroparesis (GP, n = 20) and another
      group paired by age and duration of diabetes without any complaint of autonomic
      neuropathy (DC, n = 20). They were evaluated clinically and submitted to a
      battery of five cardiovascular autonomic tests. The presence and severity of
      autonomic neuropathy were defined according to the number of normal
      cardiovascular tests. Each test had a score: zero (normal), one (borderline) and
      two (abnormal). The GP group showed a higher abnormal total score in the
      cardiovascular autonomic test than the group without any complaint (6.6 +/- 3.0
      vs. 2.7 +/- 1.4, p < 0.01). These data suggest that diabetic with gastroparesis
      presents more abnormal cardiovascular autonomic tests than diabetic without
      autonomic neuropathy and these tests should be included in the evaluation of
      diabetic patients with gastroparesis.

PMID- 9629383
TI  - [Postoperative mortality in infective endocarditis: determinant factors].
AB  - The factors leading to high postoperative mortality in active infectious
      endocarditis (IE) are poorly defined. We studied patients operated at an
      University Hospital between March 1978 and April 1992. We hypothesized that the
      summation of potential adverse factors would strongly increase mortality after
      surgery. We studied 39 patients (28 men), age range 13-70 years (mean +/- SD = 32
      +/- 16) operated during active IE (time from onset 52 +/- 48 days). Predisposing
      factor: rheumatic valvar disease in 14 cases, intravenous drug use in 5. Affected
      valves: aortic in 14, mitral in 10, tricuspid in 8, multiple structures in 7. In
      most cases, S aureus (12) or Streptococcus sp (10) was isolated in blood
      cultures. Surgery was indicated in most patients because of heart failure (30),
      multiple embolic complications (17) or treatment failure (14). The possible
      adverse influence of specific demographic characteristics, clinical features and
      surgical variables was assessed by the Student t test or the chi 2 test. Also,
      multiple regression analysis was performed in order to identify independent
      adverse factors for increased mortality. Positive correlations were further
      investigated with the chi 2 test to assess whether an increasing number of
      adverse factors could identify a special subset of patients with markedly
      elevated death risk. Fourteen patients (36%) died after surgery. Emergency
      surgery (p = 0.001), the presence of coma 6 hours after surgery (p = 0.0015) and
      S. aureus infection (p = 0.023) were all associated with increased mortality. The
      presence of neurological complications was correlated with a high mortality (54%
      vs. 27%). However this increase was of dubious statistical significance (p =
      0.097). Multiple regression analysis confirmed S. aureus and emergency surgery as
      independent adverse factors for increased mortality. When put together, an
      increasing number of adverse factors was highly predictive of a fatal outcome,
      even after exclusion of that evaluated after surgery (level of consciousness).
      Patients with two or three adverse factors had a very high mortality rate (>
      76.9%). Mortality following surgery for active IE is increased in patients
      operated on an emergency basis especially if the infection is caused by S.
      aureus. The presence of neurological complications may also be associated with
      worse outcome. Early consideration of surgery should reduce the high mortality in
      patients with active IE.

PMID- 9629384
TI  - [Etiological and clinical characteristics of infectious optic neuritis].
AB  - Fifty-one patients with infectious optic neuritis (ION) with no associated
      choroidal or retinal involvement were studied in relation to the etiologic
      agents, and to the epidemiological and clinical features to look up features
      which could be used to distinct them from the demyelinating optic neuritis (DON)
      which have a well-known tendency to convert to multiple sclerosis. Bilateral
      involvement was found in 23 patients (45.1%), simultaneously in 18 cases. Sex
      distribution was 2M:1F. The ages ranged from 1 to 82 years (median 34.8); 1/3 of
      the patients were younger than 20 and 1/3 were 50 years of age or older. Syphilis
      was found in 19 patients being the single most common etiology, whereas viral
      infections were found in 41.2% of the cases. Visual acuity was severely damaged
      in most patients and was worse than 20/200 in 57.3% of the involved eyes. Color
      vision was affected in 91.8%. Visual field defects were found in 92.2%, with
      predominance of the central defects (40.7%). The optic disc was abnormal in 90.5%
      of the eyes. This study clearly demonstrates that ION and DON have distinct
      epidemiological and clinical features. The awareness of these differences may
      help clinicians to follow different paths for the correct diagnosis and
      appropriate treatment and prognostic orientation of their patients.

PMID- 9629385
TI  - [Characterization of mitochondrial myopathies through the evaluation of the
      enzymatic activities involved in energy metabolism].
AB  - The activities of the enzymes NADH dehydrogenase, NADH cytochrome e reductase,
      succinate dehydrogenase, succinate cytochrome e reductase, cytochrome c oxidase
      and citrate synthase in normal and sick human skeletal muscle mitochondria were
      determined. A control group was formed by 13 normal people and without using
      continuous medication. The patient group was formed by 10 people whose
      pathological diagnosis indicated suspicion of mitochondrial myopathy. A decrease
      in the activity of the enzymes in all patient was observed: 7 with abnormality in
      all the tested enzymes; 2 with deficiencies in all the enzymes except cytochrome
      e oxidase; and 1 with dysfunction only in the activities of succinate
      dehydrogenase and succinate cytochrome e reductase. The results indicate multiple
      or combined deficiencies in the respiratory chain, besides dysfunction of citrate
      synthase in 9 patients. In one exceptional case, the enzymatic deficiency was
      restricted to complex II. It is possible to conclude that the methodology used
      herein is adequate and easily applicable to clinical objectives, and that the
      results obtained allow characterization of the deficient mitochondrial enzymatic
      complexes, thus showing that the origin of the diseases is an energetic metabolic
      dysfunction.

PMID- 9629386
TI  - [Evoked potentials in neurocysticercosis].
AB  - In 25 patients with cysticercosis of central nervous system, classified in two
      clinical forms, benign and malign, evoked potentials were obtained. Normal exam
      was found in 9 cases with the benign form. From 4 patients with malign clinical
      presentations, 2 had multiple abnormalities of the evoked potentials, and F wave
      alterations (mixed pattern). The authors suggest that this mixed pattern may be
      indicative of severe prognosis.

PMID- 9629387
TI  - [Subdural effusions in children. Pathophysiology and treatment].
AB  - Nine children harboring subdural effusions were treated by subduro peritoneal
      shunt. These patients were followed-up by CT scans. The area of the subdural
      effusions was measured by quantitative morphology with a planimeter. With the
      surgical treatment, the subdural effusion disappeared completely or near
      completely in 8 patients. The patient's functional state were excellent in 4,
      good in 3 and bad in 2 in the postoperative follow-up. We aldo reviewed the
      literature as far as the pathophysiology and the treatment of the subdural
      effusions are concerned.

PMID- 9629388
TI  - Hemangioblastoma of the posterior fossa. The role of multimodality treatment.
AB  - The authors made a review of a series of patients with hemangioblastomas of the
      posterior fossa treated between 1973 and 1993. A total of 32 patients were
      analyzed with 24 patients receiving resection, 8 patients receiving radiosurgery
      and 2 patients receiving conventional radiotherapy. The mortality in the patients
      with a resection was considered acceptable with 2 deaths (8%) and with a
      morbidity of 3 patients (12.5%). A review of the literature suggests that
      conventional radiotherapy with high doses (45-60 Gy) may have a role in the post
      operative control of hemangioblastomas and in some cases could be employed even
      before the resection in order to facilitate the surgery. The radiosurgical
      treatment is regarded like adjuvant. Poor results were obtained with radiosurgery
      in large tumors where low doses (less than 20 Gy) were used. Because of the
      rarity and complexity of these tumors, mainly when associated with von Hippel
      Lindau disease, a multicenter study could be useful with the assessment of the
      optimal utilization and combination of these treatment modalities.

PMID- 9629389
TI  - Cerebral aneurysms. Assessment of 50 cases operated on and comparison with
      previous series.
AB  - A retrospective analysis of 50 patients who suffered subarachnoid hemorrhage
      (SAH) treated at UNICAMP between April 1988 and March 1992 is made, distributed
      as 34% in Hunt & Hess grade I, 38% in grade II, 16% in grade III, and 12% in
      grade IV. Males were predominant (66.6%), and patients age varied around 47 +/-
      12.13 years old. Only 13 patients (26%) were admitted within the first 24 hours
      after bleeding, with an overall average of 20.45 days of delay. From all cases
      only one had a rebleeding, survived and was submitted to surgery. Four patients
      died after surgery (8%). Timing of operation and prognostic chances were
      available, being 27.30 days after SAH for Hunt & Hess group I. It is analyzed
      also the timing for diagnosis-which responded for the most delay, and treatment
      for the other groups, and a historical comparison with previous series since year
      1956 of the same Hospital were documented. Good results were observed in 38 cases
      (76%). The overall results in terms of mortality and morbidity is, in comparison,
      in accordance with the literature, and is ameliorated from the past series due to
      technical improvement, despite worsen difficulties in managing admittance,
      diagnosis and treatment faster, which is required to deal with the disease.

PMID- 9629390
TI  - [Brain metastasis of malignant melanoma. Analysis of 13 cases].
AB  - The authors present a retrospective review of 13 patients with the diagnostic of
      intracranial metastatic malignant melanoma. Their ages ranged from 28 to 84
      years. The time interval from diagnosis of primary tumor to development of
      cerebral metastases ranged from 6 to 60 months. There was preoperative evidence
      of extracranial disease in 9 patients. All patients underwent craniotomy, and the
      30-day mortality was zero. The patients survived 2 to 55 months after surgery.
      Medium survival time for all patients was 14 months. The excision of metastatic
      melanoma from the brain, although not curative, may increase survival in patients
      with this metastatic cancer. The criteria for consideration of surgery,
      radiotherapy and chemotherapy are discussed.

PMID- 9629391
TI  - [Changes found in the brain of people over 65 years old and their correlation
      with Alzheimer disease].
AB  - Twelve brains of individuals with more than sixty-five years were studied. These
      samples were submitted to three techniques, with the objective to detect senile
      plaques which the major component was the beta-amyloid; beta-amyloid
      immunohistochemistry; Glees technique; and haematoxilin-eosin technique. We
      detected significant differences between the number of senile plaques found in
      different techniques. beta-amyloid immunohistochemistry was more efficient. This
      is very important because we can underdiagnosis Alzheimer's disease when the most
      adequate technique is not used. The statistical analysis showed no significant
      differences neither between the number of cortical plaques and the hipocampal
      plaques, nor between the number of plaques in both hemispheres. A literature
      review about neuropathological findings and beta-amyloid importance was done.

PMID- 9629392
TI  - [Neurogenic pulmonary edema. Report of 2 cases].
AB  - Neurogenic pulmonary edema is a rare and serious complication in patients with
      head injury. It also may develop after a variety of cerebral insults such as
      subarachnoid hemorrhage, brain tumors and after epileptic seizures. Thirty six
      patients with severe head injury and four patients with cerebrovascular insults
      treated in Intensive Care Unit of HC-UNICAMP from January to September 1995 were
      evaluated. In this period there were two patients with neurogenic pulmonary
      edema, one with head injury and other with intracerebral hemorrhage. Diagnosis
      was made by rapid onset of pulmonary edema, severe hypoxemia, decrease of
      pulmonary complacence and diffuse pulmonary infiltrations, without previous
      history of tracheal aspiration or any other risk factor for development of adult
      respiratory distress syndrome. In the first case, with severe head trauma,
      neurogenic pulmonary edema was diagnosed at admission one hour after trauma,
      associated with severe systemic inflammatory reaction, and good outcome in three
      days. The second case, with hemorrhagic vascular insult, developed neurogenic
      pulmonary edema the fourth day after drainage of intracerebral hematoma and died.

PMID- 9629393
TI  - [Intracranial pressure monitoring as a complementary tests for diagnosing brain
      death. Preliminary observation through the report of 2 cases].
AB  - The clinical evolution of two patients with continuous intracranial pressure
      (ICP) monitoring, admitted to the Intensive Care Unit of Neurology, University
      Hospital of Botucatu, and followed until irreversible cardiac failure (ICF) was
      studied retrospectively. The evolution of ICP showed that it reached a maximum 5
      to 12 hours before a decrease in wave amplitude occurred (this was observed
      approximately 47 to 60 hours before ICF). The tracing became linear approximately
      30 hours before ICF in both cases. The clinical diagnosis of brain death (BD) was
      obtained 3 to 28 hours after the tracing had become linear. The authors suggest
      that, in absence of sedation, the diagnosis of BD may be made early with the use
      of ICP monitoring even before the clinical diagnosis, and emphasize the need for
      more observations in a larger number of patients.

PMID- 9629394
TI  - Guillain-Barre syndrome and head trauma. Case report.
AB  - The authors report the case of a 29 years old male patient presenting classical
      Guillain-Barre syndrome following head trauma. Only one other similar case is
      described in the literature. Head trauma as a precipitating event of the disease
      is discussed.

PMID- 9629395
TI  - [Intraspinal enterogenous cyst. Case report].
AB  - The authors report the case of a 7 years old boy with cervical pain and
      tetraparesis progressing by two months. He presented an intraspinal cystic lesion
      from C4 to C6. Exeresis of the lesion was undergone by anterior way through a
      corpectomy of C5-C6 followed by reconstruction with bone graft of the iliac crest
      and metallic plaque. Anatomic diagnosis of the lesion was enterogenous cyst.
      Aspects of clinical presentation, embryology and treatment of these cysts are
      discussed.

PMID- 9629396
TI  - Adult T-cell leukemia-lymphoma in a patient with HTLV-I/II associated myelopathy.
AB  - Chronic myelopathy associated with T-lymphotropic virus type I (HAM) has been
      described as an endemic disease in several areas of the world, meanwhile there
      are few papers describing the association between HAM and adult T cell leukemia
      lymphoma. We report the case of a man that, after four years of progressive
      spastic paraparesis and neurogenic bladder, developed a clinical picture of a
      lymphoproliferative disorder characterized by dermal and systemic involvement,
      mimicking mycosis fungoides/Sezary syndrome.

PMID- 9629397
TI  - [Angelman syndrome: a frequently undiagnosed cause of mental retardation and
      epilepsy. Case report].
AB  - The authors describe the case of a typical Angelman syndrome patient. The proband
      presents developmental delay, mental retardation, macrostomia, wide-spaced teeth,
      seizures, absent speech, jerky gait, and paroxysms of laughter. The cytogenetic
      and molecular studies showed a maternal deletion of 15q11q13. These results are
      in agreement with the clinical diagnosis of Angelman syndrome.

PMID- 9629398
TI  - [Auditory behavior monitoring after bacterial meningitis. Case report].
AB  - Bacterial meningitis is the main cause for acquired hearing loss. Nevertheless
      very little has been written about the development of the auditory behaviour
      either for improvement or for deterioration, after hospital release. The present
      study describes the case of a five month old boy with Haemophilus influenzae
      meningitis. Amongst various complications, a decrement in the auditory acuity was
      detected in the immediate evolution, with significant improvement later on by
      qualitative and quantitative tests.

PMID- 9629399
TI  - Frequency of the different mutations causing spinocerebellar ataxia (SCA1, SCA2,
      MJD/SCA3 and DRPLA) in a large group of Brazilian patients.
AB  - Spinocerebellar ataxia type 1 (SCA1), spinocerebellar ataxia type 2 (SCA2) and
      Machado-Joseph disease or spinocerebellar ataxia type 3 (MJD/SCA3) are three
      distinctive forms of autosomal dominant spinocerebellar ataxia (SCA) caused by
      expansions of an unstable CAG repeat localized in the coding region of the
      causative genes. Another related disease, dentatorubropallidoluysian atrophy
      (DRPLA) is also caused by an unstable triplet repeat and can present as SCA in
      late onset patients. We investigated the frequency of the SCA1, SCA2, MJD/SCA3
      and DRPLA mutations in 328 Brazilian patients with SCA, belonging to 90 unrelated
      families with various patterns of inheritance and originating in different
      geographic regions of Brazil. We found mutations in 35 families (39%), 32 of them
      with a clear autosomal dominant inheritance. The frequency of the SCA1 mutation
      was 3% of all patients; and 6% in the dominantly inherited SCAs. We identified
      the SCA2 mutation in 6% of all families and in 9% of the families with autosomal
      dominant inheritance. The MJD/SCA3 mutation was detected in 30% of all patients;
      and in the 44% of the dominantly inherited cases. We found no DRPLA mutation. In
      addition, we observed variability in the frequency of the different mutations
      according to geographic origin of the patients, which is probably related to the
      distinct colonization of different parts of Brazil. These results suggest that
      SCA may be occasionally caused by the SCA1 and SCA2 mutations in the Brazilian
      population, and that the MJD/SCA3 mutation is the most common cause of dominantly
      inherited SCA in Brazil.

PMID- 9629400
TI  - Discrepancy, coincidence or evidence in chronic idiopathic spastic paraparesis
      throughout the world. A meta-analysis on 2811 patients.
AB  - HTLV-I has been associated with a chronic idiopathic spastic paraparesis (CHISPA)
      in man; however, a complete understanding of this association is still debated.
      We selected the most comprehensible papers on this topic between 1985 and 1996,
      and found that 1261 out of 2811 patients (44.9%) reported, throughout the world,
      were HTLV-I positive. The mean age was 39.5 years and there was a female
      predominance of 1.9:1. These results do not exclude the causality of HTLV-I as a
      germen associated to CHISPA; however, other causes (e.g., toxic,
      immunosuppressors) must be considered as participating in the multistep
      neurodegeneration observed in CHISPA throughout the world.

PMID- 9629401
TI  - Propranolol vs flunarizine vs flunarizine plus propranolol in migraine without
      aura prophylaxis. A double-blind trial.
AB  - Fourty-five migraine without aura patients underwent a parallel double-blind
      trial aiming the comparison of the effects of propranolol 60 mg/day to
      flunarizine 10 mg/day and to propranolol 60 mg/day plus flunarizine 10 mg/day
      simultaneously. There were 3 groups, each one with 15 patients. After a 20-day
      baseline period, each group received one kind of treatment during 120 days.
      Migraine index on propranolol was 23.4*, on flunarizine 18.7* and on both drugs
      14.4*, mean frequency of attacks on propranolol was 1.26**, on flunarizine 1.2**
      and on both drugs 1.13** (*p < 0.05, **p < 0.01 compared to baseline) and global
      evaluation was reduced with all forms of treatment. It was not found statistical
      differences between groups, nevertheless there was a trend in the group using two
      drugs reaching lower values in migraine index, frequency of attacks and global
      evaluation. In individuals using flunarizine (alone or associated with
      propranolol) the therapeutic effect was largely maintained up to 45 days after
      drug withdrawal.

PMID- 9629402
TI  - Epilepsy surgery without invasive EEG. Early results of a new program.
AB  - A total of 42 patients were submitted to a clinical, behavioural and
      neuropsychological evaluation with the objective of eventual surgical treatment
      of epilepsy refractory to the usual clinical therapies. Prolonged video-EEG
      monitoring, MRI hippocampal volume measurement, lateralization of speech and
      memory using the amobarbital (Wada) test were used. Of 18 operated cases, 12 were
      submitted to temporal lobectomy, with a follow-up of 6-30 months; 8 patients had
      significant improvement in seizures control; 2 patients had partial improvement
      in seizure frequency and intensity; 2 patients had no improvement in seizure
      control. One patient underwent right frontal lobectomy with total remission of
      seizures and 5 had callosotomy with varying degrees of success. There was no
      mortality. Morbidity included one subdural hematoma, one transient hemiparesis,
      one episode of mania, one lobar pneumonia and frequent immediately post-operative
      muscular tension headaches. These early results indicate good results of temporal
      lobectomy patients investigated through a non-invasive presurgical evaluation.

PMID- 9629403
TI  - Comparison of MRI-guided and ventriculography-based stereotactic surgery for
      Parkinson's disease.
AB  - Stereotactic surgery for Parkinson's disease can be performed using different
      neuroimaging methods. Ventriculography has been used to locate the coordinates of
      the structures close to the third ventricle. Although it has several potential
      disadvantages related to the intraventricular injection of iodine contrast, it is
      considered a precise method. Computed tomography and magnetic resonance imaging
      have been used in some centers. In order to compare their efficacy, 50
      stereotactic thalamotomies for Parkinson's disease were performed using either
      ventriculography (VE) (25) or magnetic resonance imaging (MRI) (25). In 14 out of
      25 VE procedures, computed tomography (CT-scan) was also used and showed a
      significant mean difference of coordinate Y and Z. The clinical results employing
      either VE or MRI were similar, with 80% abolition of tremor in the VE group, and
      84% in the MRI group, after a follow up period of at least 3 months. Another 12%
      of VE and 16% of MRI group showed significant improvement of tremor. Complication
      rate was 4% in both groups. MRI-guided stereotactic thalamotomy in Parkinson's
      disease has shown good clinical results, comparable to VE-guided stereotaxis.

PMID- 9629404
TI  - [Botulinum toxin A: experience in the treatment of 115 patients].
AB  - Botulinum toxin A is the more efficient therapy of focal dystonias and hemifacial
      spasm. Our experience with botulinum toxin A injections in 115 patients is
      reported. Marked or total improvement was achieved in all 45 patients with
      hemifacial spasm, in 70% of 20 patients with essential blepharospasm and in 71.4%
      of 14 patients with Meige's syndrome. In 65.2% of 23 patients with cervical
      dystonia marked but no total improvement was obtained. The worse results were
      seen in the 6 patients with hand dystonia (writers cramp), in whom marked
      improvement was obtained in just two. Mild and transient complications occurred
      in up to 24.4%, eyelid ptosis and eyelid weakness being the most frequent. One
      patient with Meige's syndrome had an aspiration pneumonia following dysphagia.
      Our results are in agreement with others, showing that botulinun toxin A is a
      useful and safe treatment for these conditions.

PMID- 9629405
TI  - [Basilar ectasia and stroke: clinical aspects of 21 cases].
AB  - Ectasia of the basilar artery (EB) occurs when its diameter is greater than
      normal along all or part of its course, and/or when it is abnormally tortuous. EB
      may cause cranial nerve dysfunction, ischemic stroke or subarachnoid hemorrhage,
      pseudotumor or hydrocephalus. We tried to describe cases of stroke associated
      with EB, analyze its frequency, clinical aspects, and the mechanisms involved in
      different forms of its presentation. We found 21 patients with stroke and EB. The
      association between EB and stroke was more prevalent in males over the age of
      fifty. Main symptoms were hemiparesia, cranial nerves dysfunction, and cerebellar
      ataxia. Cerebral infarcts associated with EB were due to different mechanisms:
      arterial thrombosis, artery-to-artery embolism, mass effect with angulation and
      obstruction of the vertebral and basilar branches.

PMID- 9629406
TI  - [Basilar ectasia and stroke: imaging features in 21 cases].
AB  - Ectasia of the basilar artery (EB) may cause different clinical manifestations,
      and its analysis by imaging methods is fundamental. We tried to analyse
      radiological aspects in 21 patients with stroke and EB. In all of them, diagnosis
      could be done by computed tomography. However, magnetic resonance was the most
      complete diagnostic method for the evaluation of the relationship between EB an
      surrounding structures.

PMID- 9629407
TI  - [Causes of unjustified hospital stay following cerebral infarction].
AB  - The frequency and causes of prolonged length of stay (LOS) in patients with acute
      ischemic stroke were studied in 20 patients admitted to a university hospital
      participating in the International Stroke Trial (IST). The protocol for prolonged
      LOS study designed by R. S. Goldman et al. (1996) was reproduced. Mean (+/- SD)
      LOS was 13.1 +/- 11.5 days (median = 10 days). Prolonged LOS occurred in 12 (60%)
      patients. In these 12 patients, a total of 83 (62%) of 134 days were found to be
      unnecessary (6.9 +/- 4.6). Most of these patients remained hospitalized while
      awaiting for routinely performed tests, such as 2D echocardiogram or carotid
      Doppler. LOS was not influenced by patient characteristics (age or gender) or
      specific location in the hospital (emergency room or other). In conclusion, LOS
      and hospitalization costs can be markedly reduced in this hospital by rational
      use of already available diagnostic tests.

PMID- 9629408
TI  - [Knowledge and practices regarding stroke at a university hospital: Part 1.
      Education of the nursing staff: priorities for the treatment of cerebral
      infarction].
AB  - BACKGROUND AND PURPOSE: This study was undertaken to evaluate professionals
      working at a university hospital as to their knowledge and attitudes towards
      stroke. METHODS: Individuals working in the hospital were divided in two groups,
      health care workers (HCW) and non-health care workers (NHCW), and further
      subdivided according to level of schooling, resulting in seven strata. A closed
      questionnaire addressing epidemiology, risk factors, pathophysiology, typical
      symptoms, treatment, clinical course and personal attitudes towards smoking and
      blood pressure control, was applied to a random sample of each stratum (total n =
      309). Kruskal-Wallis test for multiple comparisons of non-parametric data was
      used. RESULTS: Significant differences between the seven groups were found.
      Knowledge was strongly associated with being a HCW and with level of formal
      education (p < 0.001), even after excluding physicians from the analysis (p <
      0.001). In NHCW groups, knowledge was not associated with level of education (p =
      0.421). In these groups, personal fear of suffering a stroke was the only
      variable predictive of knowledge. Smoking and poor monitoring of blood pressure
      levels were also more common in strata with the lowest levels of education and
      among NHCW. CONCLUSION: Poor knowledge and wrong attitudes towards stroke are
      frequent among individuals working in a Brazilian university hospital. Although
      these results are not necessarily applicable to the general population, they will
      certainly be useful for the development of educational programs on stroke.

PMID- 9629409
TI  - [Knowledge and practices regarding stroke at a university hospital: Part 2.
      Medical education in the new era of treatment of cerebral infarction].
AB  - BACKGROUND AND PURPOSE: This study was undertaken to evaluate professionals
      working at a University Hospital as to their knowledge and attitudes towards
      stroke. METHODS: Individuals working in the hospital were divided in two groups,
      Health care workers (HCW) and non-Health care workers (NHCW), and further
      subdivided according to level of schooling, resulting in seven strata. A closed
      questionnaire addressing epidemiology, risk factors, pathophysiology, typical
      symptoms, treatment, clinical course and personal attitudes towards smoking and
      blood pressure control, was applied to a random sample of each stratum (total n =
      309). The physicians group included 48 individuals. Kruskal-Wallis test for
      multiple comparisons of non-parametric data was used. Special attention was given
      to the wrong answers. RESULTS: Physicians correctly answered 92.6% of the
      questions. Their performance was superior to that of all other groups in all
      subgroups of questions. However, a large number of errors was found in questions
      addressing mortality and hospital mortality following stroke and the intimate
      relation between coronary and cerebral atherosclerosis. Treatment options in
      cerebral infarction are also poorly recognised. CONCLUSIONS: Although physicians
      general knowledge about stroke is good, they frequently do not perceive it as a
      critical disease requiring urgent hospital evaluation and care. The importance of
      a thorough cardiac evaluation following stroke and of the intimate relation
      between cardiac and cerebral ischemic disease is also unclear to this group. More
      hours of stroke teaching and practical training in stroke could possibly fill
      these gaps.

PMID- 9629410
TI  - [Clinical and laboratory characteristics of pyogenic meningitis in adults].
AB  - We reviewed the charts of 176 adult patients, admitted with a diagnosis of acute
      bacterial meningitis, in the Hospital Couto Maia, from January 1990 to December
      1992. All the patients had community-acquired meningitis. In 120 patients we
      could identify the causative agent on Gram's staining and culture. The most
      common pathogens were N. meningitidis (56.7%) S. pneumoniae (37.5%) and E. coli
      (3.3%). The overall lethality rate was 19.8% and the lethality was greater in the
      group with streptococcus meningitis (31.8%). The mean age and the leukocyte in
      the peripheral blood were greater in the group with S. pneumoniae meningitis than
      in the meningococal group. Cutaneous hemorrhagic lesions was and excellent
      predictor meningococcal meningitis.

PMID- 9629411
TI  - [Laboratory and clinical variables in the differential diagnosis of aseptic and
      pyogenic meningitis in children].
AB  - We reviewed the charts of 573 children with a final diagnosis of pyogenic or
      aseptic meningitis, who were hospitalized in a large reference hospital for the
      treatment of infectious disease, from January 1990 to December 1992. Seizures,
      decreased consciousness, nuchal rigidity were more frequent in bacterial than in
      aseptic meningitis. A cerebrospinal fluid (CSF) glucose level lower than 45
      mg/dL, a protein level equal or greater than 140 mg/dL and cell count greater
      than 600/mm3 were predictors of pyogenic meningitis. Receiver operating
      characteristic curve analysis was used to assess the best point in CSF measures
      of leukocytes, glucose and protein that could predict bacterial meningitis. These
      results suggest that clinicians should differentiate bacterial from aseptic
      meningitis in children with greater accuracy utilizing only clinical and simple
      CSF data.

PMID- 9629412
TI  - [Use of drugs in attention deficit hyperactivity disorders].
AB  - Attention deficit hyperactivity disorder (ADHD) is a neurological disorder which
      is common in the childhood and can be caused by exogenous and endogenous factors,
      that are responsible for cerebral disorder. This disorder presents a functional
      alteration of the motor, perceptive, cognition systems and conduct disorders
      compromising the learning of children with an adequate intellectual potential.
      The authors study the action of stimulants and antidepressive drugs in the ADHD,
      using as measure of efficacy the motor persistence tests.

PMID- 9629413
TI  - [Importance of nutritional aspects in attention deficit hyperactivity disorders].
AB  - The attention deficit hyperactivity disorder is a common childhood syndrome that
      is recognized as an important medical-social problem, being the object of an
      exhaustive investigation related to its etiology, diagnostic approach and
      prevention, and treatment forms. Among the factors that can alter the cerebral
      function, is the malnutrition. The authors discuss the association of the
      syndrome with the nutritional condition of students from elementary schools.

PMID- 9629414
TI  - Juvenile systemic lupus erythematosus. Neurological involvement.
AB  - With the purpose of analyzing the neurological involvement due to systemic lupus
      erythematosus (SLE), we evaluated 17 female patients who were seen regularly at
      the hospital and had been diagnosed as having SLE according to classification
      criteria proposed by the American College of Rheumatology revised in 1982, before
      the age of 16. Neurological involvement was detected in 12 patients (71%):
      headache (35%), extrapyramidal syndrome (35%), epileptic syndrome (24%) pyramidal
      syndrome (24%), peripheral neuropathy (12%) and optic neuritis (6%). The findings
      of CT scan (58%) and cerebrospinal fluid (50%) were most closely correlated to
      clinical neurological involvement.

PMID- 9629415
TI  - [The importance of mdx mouse in the physiopathology of Duchenne's muscular
      dystrophy].
AB  - The mdx mouse develop an X-linked recessive muscular dystrophy (locus Xp21.1) and
      lack dystrophin expression. Despite showing less intense myofibrosis and scarce
      deposition of fatty tissue, mdx mice are considered an adequate animal model for
      studies on the pathogenesis of Duchenne-type muscular dystrophy. Marked
      histological alterations in the muscular tissues associated to myonecrosis and
      inflammatory mononuclear cell infiltrate (lymphocytes, monocytes/macrophages)
      suggest a participation of the immune system in this myopathy. Modulation of the
      extracellular matrix (ECM) components in the muscular tissue during all phases
      (onset, myonecrosis and regeneration) of disease, indicate an important role for
      the ECM driving inflammatory cells to the foci of lesion. Therefore mdx mice
      should be regarded as an important tool for studies on pathogenetic mechanisms of
      Duchenne-type muscular dystrophy. Such experimental model would allow development
      of new therapeutic approaches for increasing survival and clinical amelioration.

PMID- 9629416
TI  - [Falx osteochondroma: case report and review of the literature].
AB  - One case of an intracranial osteochondroma originating from the falx is
      described. The tumor was partially removed. Surgical aspects and etiopathogenesis
      of falx chondromas are discussed. The values of computerized tomography and
      magnetic resonance are emphasized.

PMID- 9629417
TI  - [Neuroimage findings in hepatocerebral degeneration induced by hemochromatosis].
AB  - Transitory changes are shown through T1-weighted MRI bipallidal hyperintensity in
      a patient with acquired hepatocerebral degeneration induced by hemochromatosis.
      In addition we discuss about the possibility of this image associated with
      thalamic hyperintensity on T2-weighted also seen in this case, was just secondary
      to hepatocerebral degeneration, or if they could be caused by hemochromatosis
      itself.

PMID- 9629418
TI  - [Acute disseminated encephalomyelitis and meningococcal A and C vaccine: case
      report].
AB  - A 25-year-old women developed acute disseminated post-vaccinal encephalomyelitis
      (ADEM) following vaccination with A plus C meningococcal vaccine (Pasteur
      Merieux). Fast disappearance of symptoms and gradual resolution of MRI
      demyelinating lesions occurred after steroid treatment with high doses of
      intravenous methylprednisolone. To our knowledge, ADEM has not been previously
      described in association with meningococcal vaccine. Although most cases of ADEM
      occur following viral infections and vaccination, the syndrome has previously
      been related to leptospirosis and Mycoplasma pneumoniae infections. This suggests
      that it may also be related to exposure to polysaccharide-protein vaccines such
      as the Group A plus Group C meningococcal vaccine.

PMID- 9629419
TI  - [Binswanger's disease: clinicopathological study of a case].
AB  - The authors describe a case of Binswanger's disease in a female patient with
      arterial hypertension followed during 10 years, before and after the demential
      syndrome. The clinical diagnosis was established through history, clinical and
      neurological examination, and neuropsychologic evaluation. Computed tomography
      and particularly magnetic resonance imaging suggested the diagnosis, that was
      confirmed by the anatomo-pathological study. They discuss behavioral and clinical
      data, and radiological and histopathologic aspects, comparing them with data
      found in the literature.

PMID- 9629420
TI  - [De novo absence status: case report].
AB  - There are few descriptions about middle-aged patients who have nonconvulsive
      status epilepticus, absence status. We reported the clinical case of a woman, 52
      year-old, diabetic, referred to the emergency room in a confusional state.
      Initial electroencephalogram showed continuous typical, bilateral, symmetric and
      synchronous spike-and-wave discharges. Clinical and electroencephalogram
      normalization occurred immediately following intravenous injection of
      benzodiazepine. Computerized axial tomography was normal. The recognition of this
      entity is essential because of its similarity to psychiatric disturbance and its
      prompt response to proper treatment.

PMID- 9629421
TI  - Unilateral mesial temporal atrophy after a systemic insult as a possible etiology
      of refractory temporal lobe epilepsy. Case report.
AB  - Mesial temporal sclerosis is the main pathological substrate present in
      refractory temporal lobe epilepsy and its presence is often related to the
      occurrence of febrile seizures in infancy. There is an on-going discussion on the
      nature of mesial temporal sclerosis as it related to epilepsy: cause or
      consequence. A previously normal child developed hyperosmolar coma after
      abdominal surgery at the age of 6. Three months afterwards he developed simple
      and complex partial seizures with an increasing frequency and refractory to
      multiple mono- and polytherapic drug regimens. He was evaluated for surgery at
      the age of 13. Ictal and interictal recordings showed left temporal lobe
      abnormalities. Early CT scanning suggested left temporal atrophy. MRI showed
      mesial temporal sclerosis. Neuropsychological testing showed verbal memory
      deficits and he passed a left carotid artery amytal injection. He was submitted
      to a cortico-amygdalo-hippocampectomy and has been seizure-free since then. The
      clinical data obtained from this patient suggest that at least in this case
      mesial temporal sclerosis would be related to the cause of epilepsy and not
      resultant from repeated seizure activity.

PMID- 9629422
TI  - The relevance of patient individuality in the evaluation and treatment of
      aphasia. Case report.
AB  - The usual approach to language disorders relies on standardised evaluations in
      which pattern-tests characterise the subject's status according to the classical
      aphasiological typology. Those data are then analysed to support a traditional
      prevalent criterion for the distinction between "normal" and "pathological"
      linguistic performance, which is strictly focused on a quantitative approach. In
      the present study a method for evaluation and treatment of aphasia is proposed in
      which socio-cultural conditions are emphasised, in order to expand this
      conventional criterion as to encompass a qualitative (individualised) one.
      Although the methodology draws the attention, the results here obtained also
      point to the importance of re-evaluating what is presently considered as the most
      appropriate criterion for "normal" cognitive processes, particularly those
      related to language.

PMID- 9629423
TI  - [Non-hemorrhagic pituitary macroadenoma producing reversible internal carotid
      artery occlusion: case report].
AB  - The case of woman with diagnosis on non-hemorrhagic pituitary macroadenoma
      producing reversible occlusion of the internal carotid artery is presented. The
      obstruction of the internal carotid artery by a pituitary tumor is rare,
      particularly in the absence of hypophyseal apoplexy. The neuroradiological
      correlation becomes fundamentally important to demonstrate the complete occlusion
      or thrombosis of the affected vessel. The complete reestablishment of blood flow
      of the internal carotid artery after surgery becomes imperative for the complete
      symptomatological regression.

PMID- 9629424
TI  - [Neuropsychological aspects of oneiric activity: theoretical considerations
      suggested by clinical features].
AB  - Based on observations in five patients, we review the main theories concerning
      dreams and propose a comprehensive theory on their cognitive function. We
      classify dreams based on the role performed by them in inhibition, stimulation or
      creation of cognitive strategies around an emotional nucleus. These are stored in
      the memory bank and retrieved by an elicitation mechanism linking affective
      experiences on awareness and the strategies processed in previous dreams. We also
      propose that the changes in logical and emotional patterns in dreams are based on
      fronto-limbic dominance oscillations during each REM period. Preliminary
      observations we made show that awakening patients during most rapid frontal EEG
      activity REM sleep elicits more logical and less bizarre dreams. Contrariwise,
      when they are awakened during slower REM cortical EEG activity, mainly over the
      frontal lobes, their dreams are more bizarre and consequently less elaborated
      from a cognitive point of view.

PMID- 9629425
TI  - [Hereditary cerebellar ataxias: from hammer to genetics].
AB  - The hereditary ataxias comprise a complex group of neurological disorders
      involving the cerebellum and its connections. Several classifications based on
      clinical and/or pathological data have been only partially successful. Recent
      progress in molecular genetics has identified the genic loci of hereditary
      ataxias and has allowed a more precise diagnosis of distinct genetic diseases.
      Trinucleotide repeat expansions has been recognized as a mechanism of disease in
      some autosomal dominant spinocerebellar ataxias (ADCA) (SCA1 to SCA7), including
      Machado-Joseph disease/SCA3, probably the most common form of ADCA in South
      Brazil, and Friedreich ataxia (GAA expansion-chromosome 9p). Familial alpha
      tocopherol deficiency (chromosome 8q) may have a Friedreich ataxia phenotype and
      responds to the oral supplementation with vitamin E. Familial episodic ataxias
      with (EA1-chromosome 12p) and without (chromosome 19p-EA2) myokimia were
      identified, the first one caused by point mutations in the gene encoding the
      KCNA1 potassium voltage-gated channel. The gene responsible for ataxia
      teleangiectasia (chromosome 11q) was found to encode a putative DNA binding
      protein kinase (ATM), related to the cell cycle control. One to 3% of the
      population are heterozygotic ATM gen carry and pose a higher risk of cancer when
      exposed to ionizing radiation. Molecular biology has provided us with useful
      tools to diagnosis and genetic counseling and, hopefully, will provide us with a
      better understanding of the pathogenesis and eventual treatment of the several
      forms of hereditary ataxias.

PMID- 9629426
TI  - Modulation of Leydig cell testosterone production by secretory products of
      macrophages.
AB  - Unstimulated macrophages from testes inhibited the production of testosterone by
      Leydig cells from adult, but not immature, Sprague-Dawley rats (significant after
      48 h). Similar results were observed with unstimulated macrophage-conditioned
      media, suggesting that the observed effect was mediated by one or more secretory
      products. None of these substances was interleukin-1, since macrophage
      supernatants tested negative in an interleukin-1 alpha and interleukin-1 beta
      sensitive, thymocyte assay. Interleukin-6 was detected by a B cell proliferation
      assay. After stimulation by LPS, testicular macrophages enhanced testosterone
      production by Leydig cells from adult and immature rats. This enhancement was
      dose-dependent and required low concentrations (but over 2.5%) of conditioned
      media. Interleukin-1 and interleukin-6 activities were detected in LPS-stimulated
      macrophage supernatants. Supernatants of LPS-stimulated, human monocytes had
      similar effects on Leydig cells. They were rich in interleukin-1, interleukin-1
      receptor antagonist and interleukin-6. The present study suggests that, in adult
      rats, testicular macrophages modulate Leydig cell steroidogenesis by secretory
      products whose secretion depends on the physiological state of macrophages. The
      factor or factors responsible for stimulation are not species-specific. The
      effect cannot be accounted for by variations in the concentration of the above
      mentioned interleukins in macrophage supernatants.

PMID- 9629427
TI  - Evaluation of quality of spermatozoa prepared by SpermPrep method as compared to
      those prepared by MiniPercoll.
AB  - As it is quick and easy to prepare sperm with SpermPrep column, this method was
      assessed in the andrology laboratory for IUI preparations, as an alternative to
      Percoll, since Percoll is not available in market. This paper evaluates sperm
      prepared by SpermPrep method and compares them to those prepared by MiniPercoll
      for matched asthenozoospermic specimens. Spermatozoa prepared with MiniPercoll
      were of significantly higher quality, when compared with those prepared by
      SpermPrep, in terms of computer-assisted sperm motion parameters, recovery of
      motile fraction, morphology, hypoosmotic swelling and nuclear stability as
      assessed by sodium dodecyl sulphate exposure. SpermPrep did not appear to be
      equivalent to MiniPercoll and therefore could not be widely applied to
      asthenozoospermic specimens. It may be used on an individual basis, depending on
      the initial semen sample. Although other density gradient methods such as
      colloidal silica particles coated with silane appear to be equivalent to Percoll,
      they need to be critically evaluated with respect to their batches or different
      sources of vendors and be compared to Percoll as a standard method.

PMID- 9629428
TI  - Chromatin cytophotometric analysis of abnormal bovine spermatozoa.
AB  - Sperm head morphology is basically conditioned by the nuclear structure. The aim
      of the present work was to study the relation between nuclear morphological
      features, DNA content and chromatin distribution in morphologically normal vs.
      abnormal bovine spermatozoa. To this end, individual Feulgen-reacted spermatozoa
      were cytophotometrically studied. Chromatin compactation was evaluated by means
      of nuclear area, as well as mean and maximal absorbance of each nucleus.
      Morphological abnormality analysed included large, small, pear, narrow and round
      shapes, together with presumably 'diploid' sperms. Both large and small
      spermatozoa have a DNA content that does not differ significantly from normal
      values, but their area and mean and maximal absorbance are significantly
      different. Size variation seems basically due to altered chromatin compactation.
      The pear shapes have a narrower neck and a significant increase in maximal
      absorbance alone, which is invariably recorded in the neck zone whose increase
      would indicate a change in distribution and/or compactation. The narrow and round
      shapes fail to present significant variations in studied parameters. The possible
      'diploids' differ significantly from normal cells in all studied variables, with
      a little area increase.

PMID- 9629429
TI  - The outcome of clinical pregnancies following intracytoplasmic sperm injection is
      not affected by semen quality.
AB  - The objective of this study was to investigate the impact of severe
      oligoasthenoteratozoospermia (OAT) on pregnancy outcome. For this purpose 279
      consecutive intracytoplasmic sperm injection (i.c.s.i) cycles were
      retrospectively evaluated and compared to 436 consecutive IVF cycles performed
      during the same time frame. Group A (n = 62) included ICSI patients with severe
      OAT; group B (n = 217) included patients who underwent ICSI for other
      indications; and group C (n = 436) included couples who underwent standard IVF.
      The mean age of female patients and mean number of embryos transferred were
      comparable in all groups. No difference was observed regarding implantation,
      clinical pregnancy, delivery and miscarriage rates between all three groups, but
      fertilization rate was significantly lower in group A than in groups B and C. It
      is concluded that couples undergoing ICSI with severe male infertility (OAT) have
      a slightly reduced fertilization rate but their chances of delivery and pregnancy
      loss are similar to those of other patients undergoing clinical ICSI and IVF with
      non-male infertility.

PMID- 9629430
TI  - Electroejaculation and seminal parameters in bonnet monkeys (Macaca radiata).
AB  - In the present study, our experience in the collection of semen from adult bonnet
      monkeys and some of the characteristics of semen are reported. Semen samples were
      collected by penile stimulation every 15 days over a period of 3 years. The
      penile method of ejaculation was more consistent with an increased volume of
      semen. A distinct sesonality in the sperm count of the bonnet monkey was
      observed. Sperm counts were high during the months of August to October and
      started declining from November onwards. The sperm counts were significantly (P <
      0.05) higher during the mid and post-monsoon (July to November) periods than the
      pre- and early monsoon (March to June) periods.

PMID- 9629431
TI  - Effect of Percoll gradient and swim-up preparation on the chromomycin A3 staining
      of normal and abnormal semen samples.
AB  - The protamination of spermatozoa recovered by Percoll gradient and swim-up was
      investigated by means of chromomycin A3 (CMA3) staining. A total of 34 semen
      samples from patients undergoing IVF treatment were divided in two groups: normal
      (A) and oligoasthenozoospermic (B). Samples were divided in fractions, subjected
      to both techniques of preparation, and stained by CMA3. The percentage of CMA3
      positive spermatozoa recovered by Percoll was comparable to swim-up in the normal
      group. In the abnormal group Percoll resulted in significantly lower CMA3
      percentage. It is concluded that the degree of protamination in recovered
      spermatozoa is influenced by the technique of preparation.

PMID- 9629432
TI  - Effect of cold exposure on testicular delta 5-3 beta and 17 beta hydroxysteroid
      dehydrogenase activities and plasma levels of testosterone in toad (Bufo
      melanostictus) in breeding and hibernating season: duration-dependent response.
AB  - The purpose of this study was to show the effect of cold exposure on testicular
      activities in breeding and hibernating seasons in the toad. Adult male toads were
      placed in a cold chamber in both breeding and hibernating seasons for periods of
      7, 14 and 21 days. At the time of sacrifice on the 15th and 22nd days, cold
      exposed animals showed a decrease in testicular weight, testicular delta 5-3 beta
      and 17 beta-hydroxysteroid dehydrogenase activities and low levels of plasma
      testosterone both in breeding and hibernating seasons. There was no significant
      alteration in the above mentioned steroidogenic enzymes and plasma levels of
      testosterone after 7 days of cold exposure, both in breeding and hibernating
      seasons in respect to the control animals. The results of our present experiment
      suggest that environmental cold is an important modulator of breeding activities
      in the male toad. It also indicates that the breeding and hibernating cycle in
      the toad (seasonal breeders) may be asynchronous to each other.

PMID- 9629433
TI  - Electroorchidogram. A preliminary study of the electric activity of the testicles
      in dogs.
AB  - Since electric activity could be registered from various organs in the body, this
      study investigates the feasibility of recording such activity from the testicle.
      The testicles of 12 male dogs were exposed under anaesthesia and 3 electrodes
      were sutured to the tunica albuginea. In addition, transcutaneous recordings of
      the electric waves were performed. The effect of traumatic insult induced by
      testicular irradiation and by induction of hypogonadism on electric activity was
      studied. Spermatic cord clamping and orchidectomy was done to test their effect
      on the electric waves of the testicles. Electric waves were registered from the
      electrodes applied both directly and transcutaneously to the testicle. Each wave
      consisted of a negative followed by a positive deflection, with a mean frequency
      of 10.2 +/- 1.8 cycle s-1 and amplitude of 56.6 +/- 8.4 microV. The waves
      recorded from the 6 electrodes applied (3 directly and 3 transcutaneously) in the
      same animal had similar amplitude and frequency readings. No abnormal waves were
      registered. After testicular irradiation or induction of hypogonadism, a 'silent'
      or 'dysrhythmic' electroorchidogram was obtained. Spermatic cord clamping did not
      change the normal electroorchidographic pattern. No waves were recorded after
      orchidectomy (silent electroorchidogram). To conclude, an electroorchidogram was
      configurated for the normal testicle. It showed changes after testicular insult.
      It is assumed that the electroorchidogram might reveal changes in the pathologic
      conditions of the testicle and this requires further study.

PMID- 9629435
TI  - Urogenital infections and fertility.

PMID- 9629434
TI  - Influence of adenine-induced chronic renal failure on testicular function in the
      rat.
AB  - The influence of adenine-induced chronic renal failure on the male reproductive
      function was investigated using male Wistar rats. Adenine-induced chronic renal
      failure was performed in 22 rats (adenine-treated) by providing them with an
      adenine-excessive diet (150 mg adenine per day) for 10 days. An additional 22
      rats were fed without adenine-excessive diet and served as a control group. On
      days 30 and 60 after start of treatment, body weight ratio to the testis, serum
      levels of creatinine, urea nitrogen, luteinizing hormone (LH), follicle
      stimulating hormone (FSH), 17 alpha hydroxyprogesterone (17 alpha-OHP),
      androstenedione and testosterone were measured. During the experiment,
      progressive elevation of serum creatinine and urea nitrogen was found in adenine
      treated rats. Body weight ratio of the testes and serum level of LH in adenine
      treated rats were similar to those in the controls. On day 60, the FSH level in
      adenine-treated rats was significantly higher than that in the controls (P <
      0.001). While serum concentrations of 17 alpha-OHP and androstenedione in adenine
      treated rats were considerably elevated compared with those in the controls on
      day 30 (P < 0.05). These concentrations did not differ between the two groups at
      day 60. Serum testosterone level was reduced in adenine-treated rats (P < 0.001).
      This reduction was progressive with time (P < 0.05). These results suggest that
      adenine itself reduces testosterone synthesis by suppressing 17 beta
      hydroxysteroid oxidoreductase at the early stage of adenine-induced chronic renal
      failure, but that progressive renal insufficiency causes an elevation of FSH, a
      reduced synthesis of testosterone and its precursors at the late stage of adenine
      induced chronic renal failure. Thus, hormonal conditions in the male rat with
      adenine-induced chronic renal failure change with time after induction.

PMID- 9629436
TI  - Aetiopathology and pathogenesis of urogenital infections.

PMID- 9629437
TI  - Microbiology of male urethroadnexitis: diagnostic procedures and criteria for
      aetiologic classification.
AB  - Common pathogens and unconventional, fastidious bacteria, viruses, parasites, and
      fungi are causative agents in male urethroadnexitis. Uropathogens and sexually
      transmitted organisms must be considered. Diagnostic procedures and criteria for
      aetiologic classification in cases of balanitis, urethritis, prostatitis,
      epididymitis, and orchitis are described and evaluated.

PMID- 9629438
TI  - Effects of clinical stage and immunological status on semen analysis results in
      human immunodeficiency virus type 1-seropositive men.
AB  - Complete semen analyses including computer-assisted sperm motility and morphology
      assessments were performed to determine if semen and sperm differed between HIV
      seropositive men and fertile controls, or differed with symptoms, or CD4+
      peripheral cell count categories. Previous studies included small numbers of men
      and presented conflicting conclusions. Two hundred and fifty non-vasectomized HIV
      seropositive men and 38 fertile controls each provided one semen sample. Non
      parameteric statistics were used to analyse both continuous and nominal data.
      Fertile men had significantly greater semen volume, sperm concentration, percent
      motility, percent rapid and linear motility and total strictly normal spermatozoa
      than HIV seropositive men. Neither total number nor subtypes of leukocytes in
      semen differed between the two groups. Among the HIV seropositive men,
      significant differences in semen analyses were found between CD4+ cell count,
      clinical, and AIDS categories. Lower CD4+ cell counts (< 200 mm-3) were
      associated with significantly lower percent motility, percent normal sperm
      morphology by strict criteria, significantly more spermatids in semen, and higher
      percentages of teratozoospermia, oligoasthenoteratozoospermia and
      leukocytospermia. Healthier men, based on clinical categories, had significantly
      more normal shaped spermatozoa and fewer had azoospermia,
      oligoasthenoteratozoospermia or leukocytospermia. Many HIV-seropositive men have
      normal semen analyses, but as the disease progresses more defects are found,
      particularly in strict criteria sperm morphology.

PMID- 9629439
TI  - Investigations on the detection of Chlamydia trachomatis infections in infertile
      male outpatients.
AB  - The determination of Chlamydia antibodies in serum is unsuitable for diagnosing
      infertility in men. The determination of secretory IgA in seminal plasma would
      seem to be of greater relevance. Since antibodies against C. trachomatis and C.
      pneumoniae can be detected, a species-specific test for the diagnosis of
      infections of the male genital tract should be used. Only at relatively high
      titers (> or = 1:400) do genus-specific tests agree with the species-specific
      micro-immunofluorescence test. Whether such values can be taken as a true
      indicator of a local, chronic infection remains to be investigated.

PMID- 9629440
TI  - Mechanisms of sperm deficiency in male accessory gland infection.
AB  - The presence of 2 million or more peroxidase-positive white blood cells per ml of
      semen, or the diagnosis of male accessory gland infection, is associated with
      important biochemical and biological changes in semen plasma and in the
      spermatozoa, reducing their fertilizing potential in vitro and in vivo (e.g.,
      during intra-uterine insemination). In addition to the effects of reactive oxygen
      species, and its influence on the essential fatty acid composition of the sperm
      membrane, potentially unfavourable effects can occur through the intermediate of
      increased concentrations of certain cytokines, and decreased activity of enzymes
      such as alpha-glucosidase. In contrast, lower numbers of white blood cells may
      exert beneficial effects on spermatozoa thanks to the increased production of
      hepatocyte growth factor/scatter factor (a tissue repairing substance), and the
      stimulation of immuno-competent cells by particular cytokines (e.g., Interleukin
      6).

PMID- 9629441
TI  - Methods for the detection of male genital tract inflammation.
AB  - Male genital tract inflammation is reflected by increased numbers of white blood
      cells (WBC) in semen. An ejaculate containing more than 10(6) WBC ml-1 semen is
      termed leukocytospermic. Among male infertility patients, the frequency of
      leukocytospermia is between 10% and 20%. By conventional light microscopy or
      sperm staining techniques, it is not possible to reliably differentiate WBC from
      immature germ cells in semen. In contrast, the cytochemical peroxidase method
      reliably identifies granulocytes, the most prevalent WBC type in semen. The
      method is cheap, fast and easy to perform. The gold standard for the detection of
      all WBC populations in semen is immunocytology using monoclonal antibodies.
      However, it is expensive and time-consuming, thus remaining a research tool at
      present. The measurement of granulocyte elastase in semen provides information on
      the number of granulocytes and their inflammatory activation. However, commercial
      granulocyte elastase enzyme immunoassays are expensive and due to logistical
      reasons often delay the results for more than 1 week. Leukocyte esterase dipstick
      tests lack both sensitivity and specificity for the detection of inflammatory
      changes in semen. For clinical purposes, the peroxidase method is ideally suited
      to detect inflammatory changes in semen.

PMID- 9629443
TI  - Sperm morphology and male urogenital infections.
AB  - The aim of this study was to investigate the influence of urogenital infections
      as indicated by leukocytospermia on human sperm morphology, diagnosed
      cytologically and by means of a leukocyte peroxidase test. A basic semen
      analysis, including a leukocyte peroxidase test, was prospectively performed on
      150 consecutive semen samples. Cytology smears were microscopically investigated
      for the presence of WBC and the results expressed on a 4 point scale as +/- to +3
      WBCs/high power field (HPF). ROC curve analysis indicated that for cases with
      more than +/- WBC/HPF the peroxidase determined WBC count cut-off value was >
      0.25 x 10(6) WBC ml-1 with a sensitivity of 75% and specificity of 90%. The
      presence of more than +/- WBC/HPF was negatively correlated with sperm morphology
      characteristics studied. The mean (+/- SD) percentage of morphological normal
      spermatozoa was 7.0% (SD 4.4) in the WBC negative group (n = 134) compared to
      4.3% (SD 3.5) in the WBC positive (n = 16) group (P < 0.0001). There was also an
      associated increase, 15.3% (SD 13.3) to 23.6% (SD 13.8), in the percentage of
      spermatozoa with elongated head forms in the WBC positive group (P = 0.0218). No
      other effect on sperm and acrosome morphology could be found. With the peroxidase
      determinations there was also a tendency in the WBC positive group (n = 10)
      towards poorer sperm morphology characteristics, but these changes were not
      statistically significant. The presence of urogenital infections as diagnosed
      cytologically was associated with statistically poorer sperm morphology
      characteristics. This statistical relationship was not found in the peroxidase
      diagnosed leukocytospermia positive groups.

PMID- 9629442
TI  - Evaluation of seminal plasma parameters in patients with chronic prostatitis or
      leukocytospermia.
AB  - Though detailed cytological and microbiological diagnostic procedures are
      routinely carried out in male genital tract infection, the correct diagnosis and
      localization of inflammation or infection is often difficult. In this prospective
      study, the relevance of the seminal plasma markers PMN elastase, complement C3,
      CRP, fructose, PSP 94, PSA, and alpha-glucosidase was investigated in 13 patients
      with chronic prostatitis, 31 patients with significant leukocytospermia, and 58
      patients with non-inflammatory diseases (controls). Statistically relevant
      results were obtained for PMN elastase when comparing chronic prostatitis with
      controls, leukocytospermia with controls (P < 0.001) and chronic prostatitis with
      leukocytospermia (P < 0.05); for complement C3 chronic prostatitis and
      leukocytospermia vs. controls (P < 0.05) and for fructose/ejaculate
      leukocytospermia vs. controls (P < 0.05). No statistically relevant differences
      were found for C-reactive protein, alpha-glucosidase, PSA and prostatic secretory
      protein (PSP 94). To delimit genital tract inflammation from non-inflammatory
      patients, cutpoint levels for PMN elastase of 230 ng ml-1 and for C3c of 0.01 g l
      1 were suggested. PMN elastase was shown to possess the strongest discriminating
      power. The assessment of a cutpoint for fructose to indicate seminal vesicle
      dysfunction is not possible as the significance level is weak (P < 0.05).

PMID- 9629444
TI  - Influence of different uropathogenic microorganisms on human sperm motility
      parameters in an in vitro experiment.
AB  - The influence of different uropathogenic microorganisms (E. coli, enterococcus,
      Pseudomonas aeruginosa, Staphylococcus saprophyticus, Candida albicans) on human
      sperm motility was studied in vitro with a computer-assisted sperm analyser
      (CASA). Native ejaculates were prepared with the swim-up technique and adjusted
      to 22 x 10(6) spermatozoa ml-1. The sperm suspension was artificially infected
      with microorganisms in concentrations varying from 2 x 10(3) to 2 x 10(7). Sperm
      motility was examined directly after incubation, 2, 4 and 6 h later using the
      Mika motion analysis, a computer-based, automatic motility analysis. Former
      results with E. coli (serotype 06) could be confirmed that a significant
      inhibitory effect on sperm motility was associated with bacterial growth.
      Experiments with the enterococcus strain and Staphylococcus saprophyticus
      indicated no significant influence on sperm motility parameters. Tests with
      Pseudomonas aeruginosa showed a decrease of progressive motility according to
      time, but not to different bacterial concentrations. A significant inhibitory
      effect of Candida albicans was only detected in the samples with the initial
      bacterial concentration of 2 x 10(7) microorganisms ml-1.

PMID- 9629445
TI  - Antisperm antibodies and microorganisms in genital secretions--a clinically
      significant relationship?
AB  - In asymptomatic infertility patients, no significant relationship was found
      between the presence of antisperm antibodies (ASA) in serum and in semen samples
      (IgG and/or IgA ASA), differentiated with the mixed antiglobulin reaction (MAR),
      and the microbial colonization of ejaculates covering a broad spectrum of
      microorganisms. Likewise, there was no significant association of ASA with
      microbial findings in patients' female partners, who also presented without
      symptoms of genital tract infection and were screened at the same time.
      Furthermore, ASA in semen (IgG and IgA) were not significantly related to several
      potential markers of subclinical male sexual gland infection or inflammation
      (leukocytes, PMN elastase, albumin, C3c) evaluated in aliquots of the same
      ejaculates used for immunological testing.

PMID- 9629446
TI  - Influence of urogenital infections on sperm functions.
AB  - Many studies have examined the impact of genital tract infections on male
      fertility; however, the effect of bacteriospermia on sperm quality is still
      controversial. Bacterial infections are more frequently found in semen samples
      from asymptomatic infertile patients than in those from fertile men.
      Bacteriospermia is also a common problem of male partners from couples undergoing
      IVF. Therefore, the effects of microorganisms on human sperm acrosome reaction of
      oocytes have been studied in vitro and in vivo. Incubation of spermatozoa with
      Escherichia coli or Mycoplasma hominis in vitro resulted in reduced sperm
      motility and inducibility of acrosome reaction (delta AR) after exposure to
      calcium ionophore A23187. To show possible effects of E. coli and mycoplasma
      species on sperm functions in vivo, data from 488 patients were evaluated, in
      whose ejaculates microbiological examinations and determinations of acrosome
      reaction after exposure to low temperature had been performed. U. urealyticum and
      E. coli were found in semen samples from 52 and 31 men, respectively. M. hominis
      was only present in a minor number of samples and was not included in this study.
      Semen concentrations of E. coli and U. urealyticum ranged between 500-100,000 cfu
      x ml-1 and 100-80,000 cfu x ml-1. No correlation was found between delta AR and
      concentration of bacteria (Spearman rank correlation coefficient, E. coli: r
      0.081, P = 0.6644; U. urealyticum: r = -0.081, P = 0.5698). In 69% of cases with
      U. urealyticum infection and reduced inducibility of acrosome reaction, this
      sperm function was normal after antibiotic therapy. However, improvement of
      acrosomal function may only be due to intra-individual variations of acrosome
      reaction. While E. coli and mycoplasma species affect sperm functions in vitro,
      the present data and a review of the literature fail to demonstrate similar
      effects in vivo.

PMID- 9629447
TI  - Infection and reactive oxygen species.
AB  - In previous years the physiologic and pathophysiologic significance of reactive
      oxygen species (ROS) on sperm function has been recognized. The impact of ROS
      during the invasion, adhesion and multiplication of microorganisms in the male
      genital tract are largely unknown. However, it is known that the resulting
      activation of leukocytes leads to an increased generation of ROS. There is
      growing evidence that spermatozoa are protected from detrimental ROS effects by
      the powerful antioxidants in seminal plasma since disturbances of sperm function
      by ROS were demonstrated in the absence of seminal plasma, i.e., during
      epididymitis or after semen preparation. If seminal plasma is present, ROS
      generated by physiologic numbers of granulocytes (< 1 x 10(6) ml-1) apparently do
      not damage spermatozoa. Interestingly, ROS generated by leukocytes during male
      genital tract infections are critical for the techniques of semen preparation for
      assisted reproduction. These ROS impair sperm function if the protective effects
      of seminal plasma are not present. The relevance of ROS production by higher
      leukocyte numbers in human semen is presently unknown as is the relevance of ROS
      generated in the female reproductive tract.

PMID- 9629448
TI  - Therapy in male accessory gland infection--what is fact, what is fiction?

PMID- 9629449
TI  - Sperm separation in patients with urogenital infections.
AB  - A total of 196 patients attending the Center of Dermatology and Andrology,
      Giessen, Germany, were examined for fertility problems. Polymorphonuclear
      elastase, reactive oxygen species (ROS) and the number of round and peroxidase
      positive cells were investigated in addition to routine semen analysis. The
      ejaculates were also analysed before and after sperm separation by means of swim
      up or glass wool filtration. In 20 cases of leukocytospermia, sperm
      concentration, motility, viability, production of reactive oxygen species, and
      the number of peroxidase-positive cells were evaluated before and after glass
      wool filtration. The results show that ROS production by viable spermatozoa is
      highly correlated with the concentration of PMN elastase and the number of both
      peroxidase-positive and round cells. Multiple regression analysis with motility
      as dependent parameter showed the number of round cells (n = 91; r = -0.332; P =
      0.0030) to be the most important parameter affecting motility, while ROS mainly
      affects the viability of spermatozoa (n = 69; r = 0.250; P = 0.0107). In the case
      of leukocytospermia, glass wool filtration significantly reduced the number of
      peroxidase-positive cells and ROS production (P = 0.0098 and P = 0.0005,
      respectively). Receiver operating characteristic (ROC) curve analysis for ROS
      production in the ejaculate using a concentration of 1.000 ng ml-1 PMN elastase
      as decisive parameter resulted in a cut-off value of 49,489.9 counts 10(-7)
      viable spermatozoa. The statistical parameters were: Sensitivity: 63.2%,
      specificity: 100%, positive predictive value: 100%, negative predictive value:
      36.1%.

PMID- 9629450
TI  - Influence of bacteria and leukocytes on the outcome of in vitro fertilization
      (IVF) or intracytoplasmic sperm injection (ICSI).
AB  - The influence of bacteria and/or leukocytes on the outcome of IVF or ICSI is
      influenced by three factors which have little in common with in vivo conditions:
      1) The process of ejaculate preparation (swim-up, Percoll) with antibiotic
      buffered media; 2) The small amount of inseminated spermatozoa (100,000 per
      culture); 3) The short cultivation time. From the very beginning, these factors
      limit whatever the influence of bacteria and leukocytes on fertilization and
      embryonic development in vivo may be. Despite the contradictory results published
      so far, the influence of bacteria and/or leukocytes on the functional integrity
      of spermatozoa during the process of IVF or ICSI can be ignored. Furthermore,
      during IVF or ICSI the spermatozoon does not act as a vector for the
      transportation of bacteria into the ooplasm.

PMID- 9629451
TI  - Selling the benefit of education opportunities.

PMID- 9629452
TI  - Advanced practice nursing.

PMID- 9629453
TI  - Genetics in the OR--implications for perioperative nursing practice.
AB  - New developments in deoxyribonucleic acid (DNA) technology are increasing
      understanding of the role of genetics in health and disease. This kind of health
      information requires that perioperative nurses develop new skills and roles that
      will enhance the quality of genetic health care they provide to patients,
      particularly with regard to managing genetic information. Perioperative nurses
      expand their scope of practice to incorporate a genetic focus into health
      assessment, patient education, and patient support as they assimilate new genetic
      information into their daily lives. Perioperative nurses familiar with genetic
      counseling services--and how and when to refer patients for such services--will
      ensure that all patients have access to the most current and appropriate genetic
      information with which to make informed health choices.

PMID- 9629454
TI  - Minimizing patient risk during laparoscopic electrosurgery.
AB  - By the year 2000, many surgical procedures will be performed laparoscopically.
      When used appropriately, this technique is less disruptive to tissues than open
      surgery. It results in faster patient recovery time with less pain, fewer wound
      complications, and less scarring. As this technology is increasing, it is
      important to develop and implement perioperative safety precautions to reduce the
      risks associated with laparoscopic electrosurgery. Using the safety precautions
      outlined in this article may substantially reduce iatrogenic complications that
      can occur with these surgeries and result in better patient outcomes.

PMID- 9629455
TI  - Flashlamp-pumped pulsed dye laser treatment of vascular birthmarks.
AB  - Before the availability of the flashlamp-pumped pulsed dye laser (FPDL), patients
      with vascular birthmarks were treated with lasers that had a significant risk of
      scarring. For more than a decade, such patients have had the choice of being
      treated with the FPDL, which is safe, effective, and has a low risk of scarring;
      however, not all vascular birthmarks are amenable to treatment with the FPDL. The
      laser surgeon must understand the classification and natural history of the
      various vascular birthmarks to select the most appropriate therapy for a given
      patient. This article reviews FPDL treatment of port wine stains and hemangiomas,
      as well as the nursing care required for the laser procedure.

PMID- 9629456
TI  - Individual malpractice insurance decisions revisited.
AB  - Nurses' professional obligations to their patients include financial
      accountability. Whether nurses best provide this through self-insurance, coverage
      by an employer's insurance policy, or by purchase of an individual policy remains
      a personal decision. Changes in law and the health care market, however, should
      prompt a revisiting of this decision because the relative costs and benefits of
      each option may have changed. The pace of these changes, the unexpected
      consequences of some of the legal changes, and the individual differences in each
      nurse's situation may require seeking legal counsel to identify and evaluate the
      risk/benefits in that situation. The cost of that counsel may well exceed the
      cost of the policy premium.

PMID- 9629457
TI  - The ethical conduct of research.

PMID- 9629458
TI  - Occupational Safety and Health Administration acts on guidelines for
      electrosurgical smoke.

PMID- 9629459
TI  - Structure and function of the pertussis-toxin-insensitive Gz protein.
AB  - Gz is the only pertussis-toxin-insensitive member of the inhibitory G protein
      subfamily. The unique pattern of tissue distribution of Gz suggests it may carry
      out tissue-specific functions, albeit it appears to share the same profile of G
      protein-coupled receptors with Gi. The knowledge of the structural elements of
      alpha z for receptor coupling and specificity has been enriched by constructing
      chimeric molecules. Biochemical characteristics of alpha z are considerably
      different from other G protein alpha-subunits. The regulation of the GTP
      hydrolysis activity of alpha z by various GTPase-activating proteins and the
      functional impact of the PKC-mediated phosphorylation of alpha z are discussed.
      Different routes of signaling pathways that Gz could engage in have been
      explored. Furthermore, the possible involvement of Gz in retrograde axonal
      transport and various immune responses shed lights in understanding the
      physiological importance of Gz.

PMID- 9629460
TI  - G-protein-coupled receptors in vascular smooth muscle cells.
AB  - Vasoactive peptides like thrombin, angiotensin II and endothelin induce vascular
      smooth muscle cell (VSMC) contraction via activation of G-protein-coupled
      receptors. Recent studies have shown that they also induce VSMC migration and
      proliferation, processes which are important in the remodelling of the
      vasculature during embryogenesis and in the response to vascular injury. G
      protein-coupled receptor-mediated mitogenic signals appear to be transmitted via
      a number of intracellular mechanisms which include proto-oncogene gene
      expression, G-protein-mediated protein translocation and tyrosine phosphorylation
      of growth factor receptor proteins, and activation of autocrine growth factor
      pathways. The ability of vasoactive peptides to have an impact on signalling
      cascades mediated by growth factor tyrosine kinase receptors may be important in
      the pathogenesis of diseases in the vasculature.

PMID- 9629461
TI  - The evidence for G-protein-coupled receptors and heterotrimeric G proteins in
      protozoa and ancestral metazoa.
AB  - In higher eukaryotes G-protein-coupled signal transduction pathways are a common
      mechanism used to detect an extracellular message and transmit a signal, via a
      membrane-bound receptor and a heterotrimeric G protein, to second messenger
      producing enzymes and effector proteins. The techniques used to identify
      components of these pathways are increasingly being applied to protozoa and
      ancestral metazoa. Many of the organisms studied do seem to express functional
      homologues of those found in higher eukaryotes and increasingly genes encoding
      these proteins are being cloned. Sequence analysis of the isolated alpha-subunits
      of heterotrimeric G proteins shows that these proteins have extensive homology to
      their mammalian counterparts, and often show absolute sequence identity in
      functionally significant regions. The receptor clones isolated clearly establish
      that protozoa and early metazoa express proteins with seven transmembrane
      spanning domains. Comparisons with mammalian receptors indicate that these
      proteins are likely to be regulated by phosphorylation and dephosphorylation
      events, although the pathways which control these are yet to be identified. The
      postulated regulatory mechanisms and the number of homologous clones isolated
      from some protozoa suggest that a highly regulated system of transmembrane
      signalling appeared at a relatively early stage in evolution.

PMID- 9629462
TI  - G protein subunits and cell proliferation.
AB  - Heterotrimeric, guanine nucleotide binding proteins, known as G proteins, provide
      signaling mechanisms for the serpentine family of receptors. Recent studies
      indicate that the alpha- as well as the beta gamma-subunits of the G proteins are
      involved in the regulation of several cellular responses. Some of these responses
      proved to be critical for the regulation of cell growth and differentiation.
      Studies using the constitutively activated mutants of the G alpha subunits and
      the overexpression of G beta gamma subunits have indicated that these different
      subunits regulate cell proliferation through diverse signaling pathways involving
      distinct low molecular weight GTPases and specific protein kinases. The
      integrated networking between these different pathways finally defines the
      coordinated regulation of cell proliferation. This review briefly summarizes our
      present understanding of the different signaling mechanisms involved in the
      regulation of cell proliferation by the different G alpha and G beta gamma
      subunits.

PMID- 9629463
TI  - G proteins and Na+/H+ exchange.
AB  - The Na+/H+ exchangers are important regulators of intracellular pH, cell volume,
      and cell proliferation. They exist in all cells with a cell-specific pattern of
      isoform expression. Na+/H+ exchangers are regulated by a variety of extracellular
      stimuli which activate G-protein-coupled receptors and receptor tyrosine.
      Heterotrimeric G proteins regulated distinct signaling pathways, some of which in
      turn regulate the activity of Na+/H+ exchangers. This review describes the recent
      findings concerning the molecular mechanisms of the G-protein-dependent
      regulation of Na+/H+ exchangers.

PMID- 9629464
TI  - Lipid modifications and membrane targeting of G alpha.
AB  - G protein alpha-subunits (G alpha) undergo palmitoylation and/or myristoylation.
      This review will focus on new insights into the function and regulation of these
      fatty acid modifications of G alpha. Most importantly, I will examine lipid
      modifications of G alpha in the context of a two-signal model for membrane
      attachment, discuss recent advances in the identification of palmitoyl
      transferases, and highlight several controversial issues in this field.

PMID- 9629465
TI  - Exploration of the importance of the P2-P3-NHCO-moiety in a potent di- or
      tripeptide inhibitor of calpain I: insights into the development of nonpeptidic
      inhibitors of calpain I.
AB  - Calpain I, an intracellular cysteine protease, has been implicated in the
      neurodegeneration following an episode of cerebral ischemia. In this paper, we
      report on a series of peptidomimetic ketomethylene and carbamethylene inhibitors
      of recombinant human calpain I (rh calpain I). Our study reveals that the -NHCO
      moiety (possible hydrogen-bonding site) at the P2-P3 region of a potent
      tripeptide or a dipeptide inhibitor of calpain I is not a strict requirement for
      enzyme recognition. Compounds 7d ((R)-2-isobutyl-4-oxo-4-(9-xanthenyl)butanoic
      acid ((S)-1-formyl-3-methyl)butyl amide), 31 ((R)-2-isobutyl-4-(2
      sulfonylnaphthyl)butyric acid ((S)1-formyl-3-methyl)butyl amide) and 34 ((R)-2
      isobutyl-4-(2-sulfoxylnaphthyl)butyric acid ((S)-1-formyl-3-methyl)butyl amide)
      which exhibited good activity in the enzyme assay, also inhibited calpain I in a
      human cell line.

PMID- 9629466
TI  - New substituted 9-alkylpurines as adenosine receptor ligands.
AB  - In the present study an investigation of the structure-activity relationships in
      9-ethylpurine derivatives, aimed at preparing A1, A2A, A2B, and A3 selective
      adenosine receptor antagonists, was undertaken. Our synthetic approach was to
      introduce various substituents (amino, alkoxy and alkynyl groups) into the 2-, 6
      , or 8-positions of the purine ring. The starting compounds for each series of
      derivatives were respectively: 2-iodo-9-ethyladenine (9), obtained from 2-amino-6
      chloropurine (5); 9-ethyl-6-iodo-9H-purine (11), 8-bromo-9-ethyl-adenine (3) and
      8-bromo-9-ethyl-6-iodo-9H-purine (13), obtained from 9-ethyl-adenine (2). The
      synthesized compounds were tested in in vitro radioligand binding assays at A1,
      A2A, and A3 human adenosine receptor subtypes. Due to the lack of a suitable
      radioligand the affinity of the 9-ethyladenine derivatives at A2B adenosine
      receptors was determined in adenylyl cyclase experiments. In general, the series
      of 9-ethylpurine derivatives exhibited a similar pharmacological profile at A1
      and A2A receptors whereas some differences were found for the A3 and the A2B
      subtypes. 8-Bromo-9-ethyladenine (3) showed higher affinity for all receptors in
      comparison to the parent compound 2, and the highest affinity in the series for
      the A2A and A2B subtypes (Ki = 0.052 and 0.84 microM, respectively). Analyzing
      the different substituents, a phenethoxy group in 2-position (10a) gave the
      highest A2A versus A2B selectivity (near 400-fold), whereas a phenethylamino
      group in 2- and 6-position (10b and 12b, respectively) improved the affinity at
      A2B receptors, compared to the parent compound 2. The presence of a hexynyl
      substituent in 8-position led to a compound with good affinity at the A3 receptor
      (4d, Ki = 0.62 microM), whereas (ar)alkynyl groups are detrimental for the
      potency at the A2B subtype. These differences give raise to the hope that further
      modifications will result in the development of currently unavailable leads with
      good affinity and selectivity for A2B adenosine receptors.

PMID- 9629467
TI  - Theoretical descriptors in quantitative structure-affinity and selectivity
      relationship study of potent N4-substituted arylpiperazine 5-HT1A receptor
      antagonists.
AB  - The ability of ad hoc defined size and shape descriptors and theoretical
      descriptors derived on a single structure to give powerful interpretative and
      predictive QSAR models has been compared and evaluated with respect to the
      quality of the pharmacological data available for a series of structurally
      diverse 5-HT1A receptor antagonists, displaying selectivity towards the alpha 1
      adrenergic receptor.

PMID- 9629468
TI  - Camptothecin-20-PEG ester transport forms: the effect of spacer groups on
      antitumor activity.
AB  - An improved synthesis of the hindered PEG-camptothecin diester transport form has
      been achieved using the Mukaiyama reagent. We have also assessed the effect of
      changing the electronic configuration of the (d-position of PEG-camptothecin
      transport forms on the rates of hydrolysis of the pro-moiety, and attempted to
      correlate these differences to efficacy in two animal models. In addition to the
      simple substitution of N for O, other synthetic modifications of these atoms were
      accomplished by employing heterobifunctional linker groups. The half lives by
      disappearance (rates of hydrolysis) of the transport forms in buffer and rat
      plasma were determined. It was established that anchimeric assistance to
      hydrolytic breakdown of the pro-moiety occurs in a predictable manner for some of
      these compounds. Results for the new derivatives in a P388 murine leukemic model
      and HT-29 human colorectal xenograft study are also presented. The use of a
      glycine linker group was found to provide similar efficacy in rodent models to
      that of simple camptothecin 20-PEG ester, and displayed enhanced
      pharmacokinetics.

PMID- 9629469
TI  - Synthesis and radioprotective effects of adamantyl substituted 1,4
      dihydropyridine derivatives.
AB  - A series of 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid diesters
      substituted at the N-1 and/or C-4 positions of the dihydropyridine ring was
      synthesized. The in vitro cytotoxicity and in vitro and in vivo radioprotective
      efficacy of these agents were evaluated in Chinese hamster (V-79) cells and CD2F1
      male mice, respectively. Compounds with at least one adamantyl substituent
      afforded better radioprotection than those without this substituent. Substitution
      of an aromatic ring at the C-4 position of the dihydropyridine ring did not
      enhance the radioprotectant action of the compounds.

PMID- 9629470
TI  - Three new bioactive bis-adjacent THF-ring acetogenins from the bark of Annona
      squamosa.
AB  - Continuing work on the bioactivity-directed fractionation of the bark of Annona
      squamosa has resulted in the discovery of three new Annonaceous acetogenins, (2,4
      cis and trans)-squamolinone (1), (2,4-cis and trans)-9-oxoasimicinone (2), and
      bullacin B (3). Compounds 1-3 are all adjacent bis-THF ring acetogenins with 2
      representing the first bis-ring acetogenin to contain a carbonyl along its
      aliphatic chain. Compound 3 was selectively cytotoxic in a panel of six human
      tumor cell lines with a potency of nearly a million times that of adriamycin
      against the MCF-7 (human breast adenocarcinoma) cell line.

PMID- 9629471
TI  - Synthesis and antiviral activity of prodrugs of the nucleoside 1-[2',3'-dideoxy
      3'-C-(hydroxymethyl)-beta-D-erythropentofuranosyl] cytosine.
AB  - The synthesis and antiviral evaluation of 21 prodrugs of 1-[2',3'-dideoxy-3'-C
      (hydroxymethyl)-beta-D-erythropentofuranosyl ] cytosine 1 is reported. Cytosine
      N4-imine analogues were prepared by condensation of 1 with selected formamide
      dimethyl acetals. Amino acid substituted prodrugs were prepared from 1 or imine
      prodrug 2 by coupling with either N-tert-butoxycarbonyl (t-Boc)-L-valine or N-t
      Boc-L- phenylalanine in the presence of dicyclohexycarbodiimide (DCC) and 4
      dimethylaminopyridine (4-DMAP). Deprotection of the t-Boc protecting group was
      achieved with trifluoroacetic acid (TFAA) in methylene chloride. Cytosine N4
      amide analogues were prepared by reaction of 1 with appropriate anhydrides in
      aqueous dioxane. Triacylated analogue 22 was prepared by reaction of 1 with four
      equivalents of benzoyl chloride in pyridine. Prodrugs were evaluated for activity
      against duck hepatitis B virus, herpes simplex virus types 1 and 2, human
      cytomegalovirus, and human immunodeficiency virus. A number of analogues were
      found comparable in activity to 1 with the cytosine N4-imine series more active
      than the amino acid substituted and cytosine N4-amide prodrugs. Slight to
      moderate cellular toxicity was observed with some analogues.

PMID- 9629472
TI  - Synthesis of sialyl Lewis X pentasaccharide analogue for high-throughput
      screening of selectin blockers.
AB  - We have developed an effective synthesis of sLe(x) pentasaccharide glycolipid
      analogue 2. As a part of application of sLe(x) pentasaccharide glycolipid 2
      synthesized here, we have investigated the construction of a high-through-put
      screening system for discovery of selectin blockers. As a result, it was found
      that compound 2 was a useful ligand for in vitro ELISA assay and could be an
      important material for high-throughput screening of selectin blockers.

PMID- 9629473
TI  - Structure-activity relationship of HIV-1 protease inhibitors containing AHPBA.
      Part III: Modification of P2 site.
AB  - The structure-activity relationship of HIV-1 protease (HIV-1 PR) inhibitors
      containing AHPBA (3-amino-2-hydroxy-4-phenylbutanoic acid) is discussed. In order
      to solve the problem of poor oral bioavailability, small-sized dipeptide HIV-1
      protease inhibitors containing cyclic urethanes or benzamides at the P2 site were
      designed and prepared. The substitution patterns of the benzamides contributed
      significantly to their HIV-1 PR inhibitory activities, and it was shown that the
      choice of P2-residues was very important. Highly potent inhibitors possessing
      subnanomolar IC50 values and exhibiting good antiviral potency have been
      identified. In this class, inhibitor 18 was the most potent (IC90 (CEM/HIV-1
      IIIB) 0.11 microM) and showed good oral bioavailability in dogs.

PMID- 9629474
TI  - Studies on the profile of immunostimulant activities of modified iridoid
      glycosides.

PMID- 9629475
TI  - Development of agents for reinforcement of fluorescence on near-infrared ray
      excitation for immunohistological staining.
AB  - Fluorescence intensity of indocyanine green (ICG) derivative (ICG-sulfo-OSu) was
      too low for its use to detect microlesions. Therefore, we examined the effects of
      reinforcement agents on ICG-sulfo-OSu labeled antibodies. Solutions of
      distearoylphosphatic acid sodium salt (DSPA) and octylglucoside (OG) in
      physiological phosphate buffered saline (PBS) were found to increase the
      intensity of fluorescence of ICG-sulfo-OSu labeled antibodies, with shift in the
      fluorescence peak wavelength from 804 to 821 nm.

PMID- 9629476
TI  - Recovery cycles of neurons in the inferior colliculus, the pontine nuclei and the
      auditory cortex of the big brown bat, Eptesicus fuscus.
AB  - This study examines the recovery cycles of neurons in the inferior colliculus
      (IC), the pontine nuclei (PN) and the auditory cortex (AC) of the big brown bat,
      Eptesicus fuscus, using a pair of identical pulses at different interpulse
      intervals. Although the recovery cycle varies among neurons, on average, AC
      neurons have the longest recovery cycle and PN neurons have the shortest one. The
      recovery cycle of IC neurons is slightly longer than PN neurons. Neurons tend to
      have longer recovery cycles when determined with long pulse duration than short
      one. The minimum threshold of these neurons to the second pulse increases with
      decreasing interpulse interval. The difference in the recovery cycles of these
      neurons supports previous findings that IC and PN neurons can follow sound pulses
      at higher rates than AC neurons do.

PMID- 9629477
TI  - A methodological improvement and system validation to obtain precise behavioral
      parameters for schedule-induced polydipsia.
AB  - A Schedule-Induced Polydipsia (SIP) animal behaviors monitor system was devised.
      The system included a software package to acquire data and to format the data
      storage of the animal behavior in the experiment was designed. Data analysis
      software will also extract the necessary information from recorded data. The SIP
      experimental apparatus consists of a number of subsystems. They are operant
      chambers, event counters, signal acquisition and storage system. The operant
      chamber is equipped with hopper, pellet and lick sensor and locomotion detector.
      The data acquisition and storage subsystem are custom designed that run on IBM
      PC. The discrete time markers for pellet drop, bar pressing and licking water
      were recorded at 200 Hz. The image of rat locomotion was recorded at 10 Hz. A
      test of four different stages of animal to verify the accuracy of the system was
      reported in this article. The food-deprived rats that were exposed to the
      intermittent food schedule (1 per minute) exhibit an excess drinking behavior.
      The animal behaviors that were monitored during the scheduled events are
      adjunctive, facultative and terminal behavior. The volume of water intake was
      also recorded for reference. The real time data is stored chronologically into
      two types of data file. Therefore, a special data analysis procedure is designed
      to extract the results for off-line statistic analysis. The extracted parameters
      for animal behaviors analyzing including drinking efficiency, inter-lick
      intervals, number of drinking bursts, size of burst, temporal distribution of
      licking, temporal distribution of bar pressing and locomotion. The system can be
      employed in many different SIP studies such as investigating the effect of acute
      and chronic influence of amphetamine.

PMID- 9629478
TI  - Pharmacological properties of ACh receptors on the heart of the marine bivalve
      Meretrix lusoria.
AB  - The cholinergic receptors on the heart of the marine bivalve Meretrix lusoria
      were used as a model to investigate their pharmacological properties in bivalves.
      By recording method, we measured the contractile force (CF) and the heart rate
      (HR) of the heart to examine the characteristics of cholinergic receptors of a
      marine bivalve. The known ACh receptor agonists or antagonists in vertebrate
      nervous system were then introduced into the heart by perfusion, to monitor their
      effects upon heart activities. Of the six tested agonists, two mAChR agonists
      (OXA-22, bethanechol) and two nAChR agonists (methylcarbachol, nicotine) mimicked
      the response induced by ACh. Among the seven tested antagonists, three mAChR
      antagonists (trihexyphenidy1, atropine and scopolamine) and three nAChR
      antagonists (TEA, curare and hexamethonium bromide) showed the antagonistic
      effects on the inhibition induced by ACh. However, there was one mAChR agonist,
      metoclopramide, that behaved like an ACh antagonist. Both APE (mAChR agonist) and
      PTMA (nAChR antagonist) showed no significant effects. This differences suggest
      that the pharmacological characteristics of ACh receptors on the heart of bivalve
      are different from those in vertebrates. It may be a novel type of ACh receptors.

PMID- 9629479
TI  - Vascular expression of heat shock protein 72 in fructose-induced hypertensive
      rats.
AB  - Heat shock proteins (HSPs) have been implicated in protecting the cardiovascular
      system and in the pathogenesis of hypertension in stressed animals. In the
      present study, we used a fructose-induced hypertension model to explore the
      vascular expression of HSP72, the major inducible heat shock protein, in response
      to stress. Normal Sprague-Dawley rats gradually developed hypertension about 2
      weeks after feeding with fructose-enriched diet and the elevated blood pressure
      became stable 5 weeks following diet treatment. The in vivo expression of HSP72
      was absent in control rats but was transiently induced in the aorta of fructose
      fed rats during the development of hypertension. Aortic HSP72 was undetectable at
      the established phase of hypertension. The expression of HSP72 in responses to
      heat shock, or vasoactive agents were examined in cultured aortic smooth muscle
      cells. Heat shock induced the expression of HSP72 in cells from fructose-fed rats
      and age-matched control rats, and the expression levels were generally not
      significantly varied at different sampling time points in either cell source.
      Also, there was no apparent difference in the magnitude of HSP72 expression
      between two cell sources at each selected time point. Norepinephrine or
      angiotensin II induced a similar level of HSP72 expression in either cell source
      regardless of sampling time point. These data suggest that HSP72 is associated
      with the development of hypertension in this model and may exert protective
      effect on the vasculature in response to hemodynamic stress during the early
      stage of hypertension.

PMID- 9629480
TI  - Buspirone impaired acquisition and retention in avoidance tasks: involvement of
      the hippocampus.
AB  - This study investigated the effects of buspirone on acquisition as well as
      formation and expression of memory in three different types of avoidance tasks.
      Rats were trained and tested on a one-trial inhibitory avoidance task, an 8-trial
      active avoidance task or the Morris water maze. Buspirone (5.0 mg/kg) was
      administered subcutaneously 30 min before training, immediately after training or
      30 min before testing. Retention was tested at various times after training. In
      the inhibitory avoidance task, pretraining injections of buspirone produced a
      marked impairing effect on retention, posttraining injections of buspirone
      produced a moderate but time-dependent memory deficit. Pretest injections of
      buspirone suppressed retention performance. Such an effect was more pronounced in
      the 1-day test than in the 21-day test. Intra-hippocampal infusion of buspirone
      (5.0 micrograms) before testing suppressed expression of the 1-day, but not the
      21-day, memory. In the active avoidance task and the Morris water maze, an
      injection of buspirone before training or testing also impaired acquisition or
      suppressed retention performance. These findings suggest that buspirone given at
      various times could compromise acquisition, consolidation and retrieval of
      affective memory and the hippocampus was involved in the retrieval effect.

PMID- 9629481
TI  - Spike responses of sympathetic vertebral nerve activities during stimulation of
      the pressor dorsomedial and rostral ventrolateral medulla differ in cats.
AB  - In this study, we developed a differential integrator unit containing a window
      discriminator (WPI-121) and three integrators (sample/hold, Gould) to
      characterize the difference in spikes involved in sympathetic vertebral nerve
      activity (VNA) and integrated VNA (Int. VNA) during stimulation of the
      dorsomedial (DM) and rostral ventrolateral (RVLM) medullar. The upper level (UL)
      in the window discriminator was set at a value, 80% of the VNA amplitude above
      the zero. The low level (LL) was set at a value 10% above the zero. The number of
      VNA spikes above the UL in the window discriminator was defined as Fa, while the
      number of VNA spikes within the UL and LL as Fw. In 26 cats anesthetized with
      urethane and alpha-chloralose, results showed that electrical stimulation and
      microinjections of glutamate (Glu, 0.25 M, 50 nl) or glycine (Gly, 1.0 M, 50 nl)
      at the same point in DM or RVLM increased both systemic arterial pressure (SAP)
      and Int. VNA. However, the increase of Int.VNA on DM stimulation was contributed
      by increases of both Fa and Fw, while on RVLM stimulation the increase of Int.VNA
      was mainly contributed by the increase of Fa, against a decrease of Fw. As
      compared to Glu, stimulation of DM by Gly produced more increase in Fw, while
      stimulation of RVLM by Gly produced more decrease in Fw. During RVLM stimulation
      the VNA was usually transferred to a huge synchronized oscillation. These
      findings suggest that although stimulations of the sympathetic-pressor neurons in
      DM and RVLM produce similar increases in SAP and VNA, the nature of these neurons
      is different.

PMID- 9629482
TI  - The effects of methylphenidate and maturation on exploratory activity in rats.
AB  - Treatment of attention-deficit hyperactivity disorder with stimulants such as
      methylphenidate reduces motor activity and improves performance of tasks
      requiring attention, learning, and memory. The present study reports the patterns
      of behavioral activity of rats of different ages, and the effect of
      methylphenidate on the behavioral activity. The behavioral activity of Wistar
      male rats was measured on the nine hole-board apparatus. In experiment I, the
      behavioral activity of rats from three age groups (4, 8 and 12 weeks old) were
      measured in terms of the activity time, specific exploratory behavior, diverse
      exploratory behavior and defecation number. The rats were re-exposed to the hole
      board again every two weeks until they 14 weeks old. The younger rats showed
      higher activity level compared to the older rats. The activity level decreased as
      the rats grew older. The younger rats also showed more diverse exploratory
      behavior, but less specific exploratory behavior compared with the older rats.
      These suggested that the younger rats may be more hyperactive in nature, and less
      prone to focus on the specific targets. In experiment II, the methylphenidate (4
      mg/kg, i.p.) injected rats showed higher activity level than the controls across
      the three age groups. The exploratory behavioral patterns were not significantly
      different among the three age groups. This suggests that the methylphenidate
      injection raises the motor activity level without affecting the exploratory
      tendency of rats.

PMID- 9629483
TI  - La3+ inhibits the UTP-induced Ca2+ mobilization in MDCK cells.
AB  - We have studied the effects of La3+ on UTP-induced rises in intracellular calcium
      levels ([Ca2+]i) measured by fura-2 fluorimetry in Madin Darby canine kidney
      (MDCK) cells. UTP induced [Ca2+]i rises dose-dependently with an EC50 of 1 mM.
      The Ca2+ signal was triggered by a Ca2+ release from the inositol 1,4,5
      trisphosphate (IP3)-sensitive pool because the signal was completely blocked by
      pretreatment of the endoplasmic reticulum (ER) Ca2+ pump inhibitor thapsigargin
      (TG) or the phospholipase C (PLC) inhibitor U73,122. Both the peak height and
      under-curve area of 10 microM UTP-induced Ca2+ signal was reduced by
      approximately 40% by extracellular Ca2+ removal, suggesting that UTP induced
      capacitative Ca2+ entry. La3+ inhibited the UTP-induced Ca2+ signal dose
      dependently when added before or after UTP. Pretreatment of 0.1 mM La3+ inhibited
      the UTP response more than Ca2+ removal did. The mechanisms underlying the La3+
      inhibition appear to involve not only block of capacitative Ca2+ entry.

PMID- 9629484
TI  - On-line arterial blood gas analysis with optodes: current status.
AB  - OBJECTIVES: To summarize the rationale for and the principles of blood gas and pH
      measurement with photochemical sensors (optodes) placed in the arterial line-
      either intravascularly (in vivo) or extravascularly (ex vivo). To review the
      specific problems that occur with in vivo measurement; the clinical data that
      have been obtained with continuous intravascular and on-demand extravascular
      systems; and, the role of this technology in the intensive care unit. METHODS AND
      RESULTS: The principles of absorbance and fluorescent optical sensors are
      described. The accuracy of intravascular PO2 optodes can be affected by
      thrombosis, the wall effect (if the sensor touches the arterial wall it may read
      tissue values) and reduced blood flow past the sensor. Current optical pH, PCO2
      and PO2 probe/cannula designs, including hybrid probes with electrochemical PO2
      sensors, have not yet fully overcome these problems of the intravascular milieu.
      On-demand blood gas monitors that locate the optodes extravascularly, within the
      radial artery line, avoid these intravascular measurement problems. On-demand
      systems can have accuracy comparable to conventional laboratory blood gas
      analyzers. With either intravascular or extravascular measurement large patient
      studies are lacking and the relevant cost benefit ratios are not known.
      CONCLUSION: Before intravascular monitors can be used routinely for clinical
      care, reliability, consistency and accuracy will have to be demonstrated in large
      and widely divergent patient groups. Extravascular on-demand blood gas analysis
      is accurate, allows trend monitoring of blood gases and decreases the risk of
      infection, the therapeutic decision time and patient blood loss. As large patient
      studies are lacking the clinical role of on-line blood gas analysis cannot be
      clearly delineated.

PMID- 9629485
TI  - Effect of collection and preprocessing methods on neutrophil elastase plasma
      concentrations.
AB  - OBJECTIVES: Elevated plasma levels of the elastase alpha 1-proteinase inhibitor
      complex (E-alpha 1 PI) have been proposed as a marker of bacterial infection and
      neutrophil activation. Liberation of elastase from neutrophils after collection
      of blood may cause falsely elevated results. Collection methods have not been
      validated for critically ill neonates and children. We evaluated the influence of
      preanalytical methods on E-alpha 1 PI results including the recommended
      collection into EDTA tubes. DESIGN AND METHODS: First, we compared varying
      acceleration speeds and centrifugation times. Centrifugation at 1550 g for 3 min
      resulted in reliable preparation of leukocyte free plasma. Second, we evaluated
      all collection tubes under consideration for absorption of E-alpha 1 PI. Finally,
      12 sets of samples from healthy adults and 42 sets obtained from critically ill
      neonates and children were distributed into the various sampling tubes. Samples
      were centrifuged within 15 min of collection and analyzed with a new
      turbidimetric assay adapted to routine laboratory analyzers. RESULTS: One of the
      two tubes containing a plasma-cell separation gel absorbed 22.1% of the E-alpha 1
      PI content. In the remaining tubes without absorption of E-alpha 1 PI no
      differences were observed for samples from healthy adult patients. However, in
      samples from critically ill neonates or children, significantly higher results
      were obtained for plain Li-heparin tubes (mean = 183 micrograms/L), EDTA tubes
      (mean = 93 micrograms/L), and citrate tubes (mean = 88.5 micrograms/L) than for
      the Li-hep tube with cell-plasma separation gel and no absorption of E-alpha 1 PI
      (mean = 62.4 micrograms/L, p < 0.01). CONCLUSION: Contrary to healthy adults, E
      alpha 1 PI results in plasma samples from critically ill neonates and children
      depend on the type of collection tube.

PMID- 9629486
TI  - Distribution of the receptor for a novel peptide stimulating phosphoinositide
      hydrolysis in human leukocytes.
AB  - OBJECTIVES: Previously we reported that a synthetic peptide, WKYMVm, stimulates
      phosphoinositide (PI) hydrolysis in several hematopoietic cell lines and human
      neutrophils. In addition, the peptide induces superoxide generation in human
      neutrophils. The biochemical stimulation appeared to be mediated by specific
      receptors on leukocytes. In this report we try to find whether the specific
      receptor(s) exists on specific types of cells in human leukocytes. DESIGN AND
      METHODS: To study distribution of the peptide-specific receptors, we prepared a
      probe, biotin-labeled WKYMVm, and analyzed distribution of the peptide receptor
      using a biochemical study, cytochemical staining, and flow cytometric analysis.
      RESULTS: The peptide-specific receptors are expressed in several human leukocytes
      including granulocytes, monocytes, and B-lymphocytes but not T-lymphocytes and
      erythrocytes. CONCLUSIONS: These data suggest that the receptors for the peptide
      restricted to certain types of leukocytes and this specificity is probably
      related to the specific functions of the stimulated leukocytes.

PMID- 9629487
TI  - Measurement of glutamine and glutamate by capillary electrophoresis and laser
      induced fluorescence detection in cerebrospinal fluid of meningitis sick
      children.
AB  - OBJECTIVES: Cerebrospinal fluid glutamine and glutamate concentrations were
      measured by CZE-LIFD in normal and meningitis sick children. DESIGN AND METHODS:
      A derivatization procedure for glutamine was optimized using CZE-LIFD.
      Cytochemical and bacteriological analysis were made to 152 CSF from children
      suspicious of suffering meningitis. RESULTS: CSF-glutamine concentration was
      lower in children with viral and bacterial meningitis. In addition, the group
      infected with Haemophilus influenzae had the lowest concentrations. By contrast,
      glutamate concentration was higher in children with meningitis. Glutamine
      concentration increased as the clinical condition of the patient improved.
      CONCLUSIONS: Lower concentrations of glutamine in children with bacterial
      meningitis might be due to the use of this amino acid for bacterial growth while
      higher concentrations of glutamate might be due to cell destruction. The results
      indicate that CZE-LIFD is an alternative tool for the determination of amino
      acids in CSF.

PMID- 9629488
TI  - Novel hybridization assay configurations based on in vitro expression of DNA
      reporter molecules.
AB  - OBJECTIVES: To develop and study novel microtiter well based DNA hybridization
      assays in which the DNA serves as a reporter molecule. METHODS: Two hybridization
      assay configurations are proposed. In configuration A the target DNA is end
      labeled with biotin and captured to streptavidin-coated wells. The one strand is
      removed by NaOH treatment and the other is hybridized with a dATP-tailed
      oligonucleotide probe. Configuration B involves simultaneous hybridization of
      heat-denatured target DNA with a biotinylated capture probe (immobilized on
      streptavidin-coated wells) and a dATP-tailed detection probe. In both
      configurations the hybrids are reacted with dTTP-tailed luciferase-coding DNA
      fragment followed by in vitro expression of the DNA on the solid phase. This is
      accomplished either by a coupled transcription/translation or by sequential
      transcription and translation reactions optimized separately. RESULTS: The signal
      to-background ratios for configuration A at 0.93 fmoles target DNA were 2.6 and
      16.7 with the coupled and the separated transcription/translation protocols,
      respectively. As low as 0.1 fmoles target DNA can be detected with the separate
      transcription/translation protocol with a signal-to-background ratio of 2.7. The
      signal-to-background ratios obtained for 0.1 fmoles target DNA with configuration
      B using the coupled and the separate expression protocols were 2.2 and 4.6,
      respectively. The average CV was 10%. CONCLUSION: The expression yield is
      significantly improved with the separate transcription/translation protocol. Both
      assay configurations offer high sensitivity and are easily automatable.

PMID- 9629489
TI  - Cyclosporine metabolite cross-reactivity in different cyclosporine assays.
AB  - OBJECTIVES: There is a controversy regarding the role of cyclosporine (CsA)
      metabolites in both immunosuppression and toxicity, and measurement of the parent
      drug is commonly recommended. High performance liquid chromatography (HPLC) is
      the method commonly used for specific measurement of the parent drug, but is very
      time consuming. Antibody techniques are available but vary in specificity. Mixed
      lymphocyte culture assay (MLC) is a functional bioassay for the measurement of
      CsA which measures both parent drug and active metabolites. Because it is time
      consuming and labor intensive, it is not practical to use the MLC to monitor
      patient's CsA levels. The objective of this study is to evaluate the degree of
      cross-reactivity or interference among two different CsA immunoassays
      [(Immunoassay: CYCLO-Trac-RIA, Monoclonal-TDX; and two radioreceptor assays (RRA)
      (52 kDa immunophilin and cyclophilin)] with seven cyclosporine metabolites (AM19,
      AM1c9, AM4n9, AM1, AM9, AM1c, AM4n). The results are compared with a previously
      published MLC assay for the same metabolites. METHODS: 500 ng/mL of each of the
      CsA metabolites was assayed in spiked blood samples with both RRA using 52 kDa
      immunophilin and commercial cyclophilin and two commonly used commercial
      immunoassay procedures. The results were compared to those obtained with the
      previously published MLC assay. RESULTS AND CONCLUSION: The CYCLO-Trac
      radioimmunoassay showed minimal cross-reactivity with all of the seven CsA
      metabolites tested and is more specific to parent CsA than the current Abbott
      monoclonal procedure for the measurement of CsA. However the cross-reactivity of
      the seven metabolites using the Abbott monoclonal assay matched closely with
      their pharmacological potency as measured in the MLC assay. The RRAs showed
      greater cross-reactivity for most of the CsA metabolites tested than that found
      in the immunoassay procedures.

PMID- 9629490
TI  - Quantification of the variation due to lysing technique in immunophenotyping of
      healthy and HIV-infected individuals.
AB  - OBJECTIVE: We performed a side-by-side comparison between three stain-then-lyse
      commercially available methods (Ortho-mune Lysing solution, FACS lysing solution
      and ImmunoPrep reagent system) and a lyse-then-stain method using hypotonic
      NH4Cl. The major difference between these methods is that only in the latter the
      aliquots of sample to be distributed into diverse tubes for the various antibody
      combinations were obtained from a lysis step performed in the same tube. DESIGN
      AND METHODS: Lymphocytes from 20 healthy and 20 HIV+ subjects were phenotyped by
      dual color flow cytometry using a standard procedure that included the
      establishing of a lymphocyte gate on light scatter bit map and the use of the
      minimal acceptable antibody combinations, i.e., CD45/CD14, CD3/CD4 and CD3/CD8,
      according to CDC recommendations. All samples were processed in triplicate to
      assess tube-to-tube variability. RESULTS: In healthy subjects, erythrocytes pre
      lysing provided the highest purity and recovery in the lymphocyte gate, and
      allowed the best identification of CD4+ lymphocytes. Most remarkably,
      erythrocytes pre-lysing significantly outdid all other methods in reducing tube
      to-tube variability. This allowed the attainment of highest correlation between
      CD3+ cells identified by CD3/CD4 and CD3/CD8 antibody combinations and the
      minimum variability between the sum of the %CD3+CD4+ and %CD3+CD8+, and the total
      %CD3+. This higher reliability of the pre-lysis method was particularly evident
      with HIV+ patients in which the lymphocyte gate was often and unpredictably
      contaminated by debris and other cell types. CONCLUSIONS: The present study
      demonstrates that lysing erythrocytes in a single tube and distributing aliquots
      of lysed blood into different tubes for the various antibody combinations
      provides superior results for routine immunophenotyping.

PMID- 9629491
TI  - Structural characterization of two novel oxidative derivatives of cyclosporine
      generated by a chemical method.
AB  - OBJECTIVES: To study the generation of cyclosporine derivatives (CMs) by chemical
      oxidation of the parent compound using hydrogen peroxide. METHODS AND RESULTS:
      Hydrogen peroxide was added to cyclosporine (CsA), which was dissolved in ether.
      After liquid-liquid extraction, CMs were purified by high performance liquid
      chromatography (HPLC). Detailed structures of CMs were determined by fast atomic
      bombardment mass spectrometry (FABMS) and nuclear magnetic resonance spectroscopy
      (NMR). Our results indicated that the parent compound was modified at amino acid
      number 1 by hydroxylation of the carbon and the formation of a tetrahydrofuran
      five member ring structure. In addition, these two oxidative products of CsA were
      determined to be isomeric to each other, differing only in the configuration at
      one or more carbon atoms. This modification is in contrast to that observed for
      the formation of the cyclic metabolite of CsA, namely AM1c, by cytochrome P-450
      isoenzymes, where the addition of the hydroxyl group occurs on the carbon of
      amino acid 1. CONCLUSION: 3 to 4 mg of 2 oxidative derivatives could be produced
      from 5 mg of CsA by chemical modification of the parent compound. In comparison,
      biotransformation using the drug-induced hepatic microsomal enzyme system could
      only produce 0.5 to 1 mg of metabolites/derivatives from 5 mg of CsA.

PMID- 9629492
TI  - Glycosidases in the peritoneal fluid from infertile women with and without
      endometriosis.
AB  - OBJECTIVES: To investigate the activity and biochemical properties of
      glycosidases in the peritoneal fluid of infertile patients with or without
      endometriosis in comparison with fertile women. DESIGN AND METHODS: Peritoneal
      fluid was collected from 29 women undergoing a laparoscopy. The sample was
      separated into the following groups: fertile women (n = 11), infertile with
      endometriosis (n = 11), and infertile without endometriosis (n = 7). The activity
      of glycosidases was determined with specific p-nitrophenylglycosides as
      colorimetric substrates. RESULTS: The activity of alpha-fucosidase, alpha
      glucosidase, alpha-mannosidase, beta-galactosidase, beta-glucuronidase, and beta
      N-acetylhexosaminidase was investigated. Enzymatic activities of alpha-fucosidase
      and beta-N-acetylglucosaminidase were detected in higher amounts than other
      glycosidases. The activities of alpha-fucosidase and N-acetylglucosaminidase were
      increased in the case of infertile patients without endometriosis, while beta
      galactosidase was increased in endometriosis patients. Enzyme properties as pH
      optimum, pH stability, thermal stability and inhibition by specific carbohydrates
      were similar for both control and infertile samples. Analysis of kinetic
      parameters indicate that Vmax values of glycosidases were higher for infertile
      samples than their respective controls. CONCLUSIONS: The results indicate that
      higher amounts of glycosidases are present in the peritoneal fluid from infertile
      patients. The elevated activity of these hydrolytic enzymes suggest possible
      deleterious effect on gametes, and could explain some cases of infertility.

PMID- 9629493
TI  - Determination of salivary cortisol by nonisotopic immunoassay.

PMID- 9629494
TI  - Improved method for direct haplotyping at the vitamin D receptor gene locus.

PMID- 9629495
TI  - Genetic analysis of beta-thalassemia major and beta-thalassemia intermedia in
      Brazil.
AB  - The development of methodologies to identify the molecular lesions responsible
      for different types of beta-thalassemia has made it possible to correlate these
      data with clinical and hematological severity. We examined DNA from 35 patients
      with beta-thalassemia, residents of the State of Sao Paulo, Brazil, for some
      types of genetic modifying factors: beta-thalassemia mutations, the upstream Xmnl
      GY-globin gene polymorphisms, and alpha-globin gene deletions. Additionally, the
      beta-like gene cluster haplotypes and the presence of the AYT variant were
      studied. The following mutations were present in the 70 chromosomes studied:
      54.3% codon 39 (C-->T) (beta degree); 18.6% IVS-I-6 (T-->C) (beta+); 18.6% IVS-I
      110 (G-->A) (beta+), and 4.3% IVS-I-1 (G-->T) (beta degree). Haplotype II was
      associated with the nonsense mutation at codon 39, haplotype I with the IVS-I-110
      and codon 39 mutations, and haplotypes VI and VII with the IVS-I-6 mutation. The
      Xmnl polymorphism was detected in three out of 31 patients studied. No alpha
      thalassemia was detected among the thalassemia intermedia patients. The AYT
      variant was present in 87.1% of 31 thalassemia patients and was associated with
      the codon 39/haplotype II and IVS-I-6/haplotype VI mutations. This is the first
      study of the Brazilian population that has analyzed the beta-thalassemia
      mutations and other molecular variants, and has correlated them with the clinical
      manifestations.

PMID- 9629496
TI  - An alpha-thalassemic hemoglobinopathy: homozygosity for the HB Agrinio alpha 2
      globin chain variant.
AB  - This report describes the first case of homozygosity for the Hb Agrinio [alpha
      29(B10)Leu-->Pro] alpha 2-globin gene variant (codon 29, CTG-->CCG) in a Greek
      patient. At 12 months of age, the proband presented with a marked hypochromic,
      microcytic anemia, a very low level of Hb H (< 2.5%), rare Hb H inclusions, and a
      balanced alpha/non-alpha biosynthesis ratio. The mother had hematological
      findings and globin biosynthesis consistent with heterozygous beta-thalassemia,
      but paradoxically, red cell morphology demonstrated very rare Hb H inclusions.
      The father had mild microcytosis and hypochromia. Analysis of alpha- and beta
      globin genotypes demonstrated that the patient was homozygous for the highly
      unstable Hb Agrinio variant, caused by a T-->C mutation in codon 29 of the alpha
      2-globin gene. At the age of 13 years, the proband had a clinical phenotype
      compatible with mild thalassemia intermedia with moderate anemia (Hb 7-8 g/dL),
      normal growth and development, slight splenomegaly, and minimal bone changes,
      while Hb H and inclusion bodies were not detected.

PMID- 9629497
TI  - Alpha- and beta-globins of the anemic Belgrade laboratory rat. I. Status of alpha
      and beta-globins in bone marrow and spleen.
AB  - In this study we have demonstrated that the bone marrow of the anemic Belgrade
      laboratory (b/b) rat, as the primary site of erythropoiesis, has a decreased
      globin polypeptide synthesis in total protein cell extracts. Therefore, it is the
      source of red blood cells containing decreased amounts of globin mRNAs and
      polypeptides. In spite of the fact that the b/b rat shows a splenomegaly, the
      spleen is not capable of compensating for the anemic state. Spleen erythroid
      cells are defective in differentiation and contain a decreased share of globin
      polypeptides in total protein cell extracts compared to the control. Spleen cells
      are also characterized by a drastic imbalance of alpha- to beta-globin resulting
      in the beta-globin chains surplus.

PMID- 9629498
TI  - Alpha- and beta-globins of the anemic Belgrade laboratory rat. II. The effect of
      hemin and iron-dextran treatment.
AB  - We have studied the changes in bone marrow and spleen globin chain levels after
      in vivo hemin and iron-dextran treatment of hereditarily anemic Belgrade
      laboratory (b/b) rats. The increase of globin chains was detected in the bone
      marrow and in the spleen when b/b animals were treated with either iron or hemin.
      The analysis of changes in alpha- and beta-globin chain ratios revealed the
      distinctive role of these molecules in regulating globin chain status. Iron
      dextran, as expected, ameliorated the imbalance of alpha- and beta-globin chains
      in the b/b rat spleen. On the other hand, hemin, as we have hypothesized in the
      accompanying paper, leads to a surplus of beta-globin chains in the bone marrow,
      similar to the one detected in the b/b rat spleen. Therefore, an iron-rich
      microenvironment has a stimulatory effect, while a hemin-rich microenvironment
      has an inhibitory effect on erythropoiesis.

PMID- 9629499
TI  - Pharmacologic hemoglobin reversal: the importance of lipid intermediaries and the
      proposed involvement of the cAMP and phosphatidylinositol second messenger
      systems.
AB  - Humoral and microenvironmental influences have played a major role in recent
      research into reversing the Hb F to Hb A switch. Early research in this area
      focused on hormonal influences and showed both thyroid hormone and prolactin
      could induce small but statistically significant reversals in hemoglobin
      phenotype. Recent research has focused on the effect of certain lipids in this
      process. The current study shows a synergy between thyroid hormone and prolactin
      in inducing a significant switch in adult rat hemoglobin patterns toward the
      neonatal pattern. Further, it is hypothesized that this synergy is due to the
      hormones' effect on lipid intermediaries whose effect in turn are proposed to be
      mediated by the cAMP and phosphatidylinositol second messenger systems.

PMID- 9629500
TI  - Familial hemolytic anemia due to Hb Sabine [beta 91(F7)Leu-->Pro] identified by
      polymerase chain reaction.

PMID- 9629501
TI  - A note about the relative elution rates of various abnormal hemoglobins and
      abnormal globin chains in cation exchange and reversed phase high performance
      liquid chromatography.

PMID- 9629502
TI  - Coexistence of Hb Lepore-Boston-Washington (delta 87Gln-beta-IVS-II-8) with alpha
      thalassemia [alpha(-5NT)alpha/alpha alpha].

PMID- 9629503
TI  - Thalassemia and hemoglobinopathies in Argentina.

PMID- 9629504
TI  - Historical note: the beta-thalassemia allele in the noble Russian family
      Lermontov is identified as the ATG-->ACG change in the initiation codon.

PMID- 9629505
TI  - The thalassemia repository (Ninth Edition; Part II).

PMID- 9629507
TI  - Lexipafant fails to improve survival in severe necrotizing pancreatitis in rats.
AB  - CONCLUSION: Lexipafant administration fails to improve survival or lessen the
      disease severity in two experimental models of severe acute pancreatitis.
      BACKGROUND: The potent platelet activating factor antagonist Lexipafant has been
      shown to attenuate the biochemical and histologic changes associated with some
      animal models of acute pancreatitis, suggesting an important role for this
      cytokine in its pathogenesis. However, a survival advantage following Lexipafant
      administration has not been demonstrated. This study evaluates the effect of this
      platelet activating antagonist on survival in rat models of necrotizing and
      fulminant hemorrhagic pancreatitis. METHODS: Sprague-Dawley rats underwent
      induction of either acute necrotizing (n = 40) or hemorrhagic pancreatitis (n =
      36) with a time- and pressure-controlled bile duct infusion of 10 mM
      glycodeoxycholic acid (GDOC) or enterokinase 15 U/mL, in combination with
      supramaximal cerulein stimulation (5 micrograms/kg/h). Immediately after
      pancreatitis induction, rats were randomly divided into three groups and received
      Lexipafant (1 mg or 10 mg) or saline as a continuous intravenous infusion over 9
      h. Twenty-four-hour survival rates were determined and severity of pancreatitis
      was assessed by pancreatic histology scores. RESULTS: The survival rates for GDOC
      treated rats were 55% (saline), 50% (1 mg Lexipafant) and 50% (10 mg Lexipafant).
      As expected, all rats induced with enterokinase and treated with saline died with
      hemorrhagic pancreatitis within 24 h. The same was true of those treated with
      high- and low-dose Lexipafant, and there was no difference in survival time.
      Histology scores did not differ between Lexipafant-treated and control rats in
      either GDOC or enterokinase rats.

PMID- 9629508
TI  - Sphincter of Oddi manometry. Paradoxical response to secretin but not to CCK in
      alcoholic patients with no pancreatic disease.
AB  - CONCLUSION: In chronic alcohol abusers with no pancreatic disease, secretin was
      found to induce a paradoxical spasmodic response in the sphincter of Oddi (SO)
      instead of the relaxation observed in controls. Cerulein, on the contrary, had a
      normal relaxing effect on the SO. BACKGROUND: We previously reported SO
      dyskinesia in cases of chronic pancreatitis. Here we investigated whether chronic
      alcohol consumption may have contributed to the genesis of this dyskinesia.
      METHODS: SO and main pancreatic duct pressures were recorded endoscopically with
      a dual electronic pressure sensor in 27 chronic alcohol abusers and compared with
      the values obtained in 15 normal controls. These pressures were recorded both in
      the basal state and after applying hormonal stimulation by injecting either
      secretin (1 CU/kg) or cerulein (75 ng/kg). RESULTS: Cerulein relaxed the SO in
      both the controls and the chronic alcohol abusers, whereas it transiently
      enhanced the main pancreatic duct (MPD) pressure. Secretin induced a wave of MPD
      hyperpressure (+15.4 +/- 3.0 mm Hg) in both groups of subjects, but in the
      alcoholic group, instead of relaxing SO, it significantly enhanced the amplitude
      of phasic contractions (+32.6 +/- 8.4 mm Hg). The SO basal pressure was also
      paradoxically enhanced by secretin in the alcoholic patients (28.8 +/- 8.2 vs
      10.1 +/- 2.4 mm Hg).

PMID- 9629509
TI  - Influence of high-dose pancreatic enzyme treatment on pancreatic function in
      healthy volunteers.
AB  - CONCLUSIONS: Adaptive changes in exocrine and endocrine pancreatic function, as
      well as changes in pancreas size and morphology, were not observed after 4-wk of
      oral pancreatic enzyme application. These findings suggest that the normal
      pancreas does not significantly adapt--either morphologically or functionally--to
      a 4-wk oral application of high-dose pancreatic enzymes. BACKGROUND: The control
      of exocrine pancreatic enzyme secretion is not completely understood. Although it
      has been established that exocrine pancreatic secretion is mainly regulated in
      the short-term by the amount of pancreatic enzymes in the proximal small
      intestine, it is not known whether long-term application of pancreatic enzymes
      causes changes in exocrine pancreatic secretion in humans. METHODS: Twelve
      healthy male volunteers (median age 27 yr) participated in a prospective,
      randomized, placebo-controlled, double-blind study. Six were placed in the
      treatment group and six in the placebo group. Over a 4-wk period, the six
      subjects in the treatment group took 18 capsules of Panzytrat (20,000 units of
      lipase, 18,000 units of amylase, and 1000 units of protease per capsule) daily.
      Before (wk 0), 4 wk following pancreatic enzyme application and 2 wk afterward, a
      secretin-cerulein test was carried out in all subjects to study exocrine
      pancreatic function (trypsin, chymotrypsin, bicarbonate content, and total
      pancreatic fluid secretion in the duodenum). One day following the secretin
      cerulein test, a standard test meal was given to all subjects to analyze
      endocrine pancreatic function. Additionally, before starting the treatment, once
      per week during treatment and 2 wk afterward, an ultrasound examination of the
      pancreas was carried out to see whether there was any change in pancreas size and
      morphology. RESULTS: Trypsin content in the duodenal aspirates following
      simultaneous stimulation with secretin and cerulein after 4 wk of high-dose
      pancreatic enzyme application was 92% in the treatment group and 82% in the
      placebo group compared with the wk 0 test results (100%). Two weeks after enzyme
      application, the secretin/cerulein-stimulated trypsin content was 88% in the
      treatment group and 107% in the placebo group. None of these changes was
      statistically significant. The same results were seen for chymotrypsin content,
      amylase, and bicarbonate content as well as for total pancreatic fluid secretion.
      Additionally, no change in the endocrine pancreatic function could be observed
      after 4 wk of pancreatic enzyme treatment. Pancreas ultrasonography revealed no
      alteration in pancreas size or parenchymal structure during the 4 wk of treatment
      and the following 2 wk.

PMID- 9629510
TI  - Different dosages of acetylsalicylic acid lead to adverse modifications of the
      reaction of rat pancreas to ethanol.
AB  - CONCLUSION: Acetylsalicylic acid (aspirin, ASA) in a therapeutic dose prevents
      lipid peroxidation and damage of cell organelles in pancreatic tissue of rats
      chronically fed with ethanol. In contrast, higher ASA dosages lead to enhanced
      biochemical and morphological signs of pancreatic damage different from findings
      in rats fed by ethanol alone. METHODS: Two groups of rats received 20% alcohol as
      drinking fluid plus a diet containing either 6 (S6) or 10 g/kg (S10) ASA. Two
      control groups received no ASA (CA) and neither ASA nor alcohol (CW),
      respectively. Feeding was performed by the interrupted feeding regimen with four
      18-h periods of food and fluid withdrawal weekly. After 7 mo, pancreatic tissue
      was examined by light and electron microscopy. In pancreas homogenates, the
      contents of malondialdehyde (MDA), protein, trypsinogen, lipase, pancreatic
      secretory trypsin inhibitor, acid phosphatase (AcPh), cathepsin B, beta
      glucuronidase, and desoxyribonucleic acid were determined. RESULTS: In the
      pancreas of group CA, we found a 100% increase of MDA compared with group CW,
      increased fat deposition, as well as damaged mitochondria (Mito) and endoplasmic
      reticula (ER) in acinar cells, decreased protein content, decreased AcPh
      activity, and unchanged secretory parameters. The ASA-fed groups showed MDA
      contents indistinguishable from group CW. Protein and secretory parameters were
      decreased. Lysosomal enzymes were decreased in S6, but in S10, they were always
      higher than in group S6 and mostly as high as in group CW. Fat deposits were as
      frequent as in group CA. Mito and ER were mostly well preserved, but more
      autophagosomes and residual bodies occurred, particularly in group S10.

PMID- 9629506
TI  - The use of molecular technology in the differentiation of pancreatic cancer and
      chronic pancreatitis.
AB  - CONCLUSION: It is concluded that currently there are limitations in the use of
      some of the proposed tests, whereas in the future, further progress in our
      understanding of the molecular biology of pancreatic disease and the development
      and application of existing techniques should have a greater impact on clinical
      practice. BACKGROUND: Fifteen to 20% of patients with pancreatic cancer present
      with a resectable mass in the head of the pancreas, but there is a subgroup of
      patients for whom it is difficult to reach the correct diagnosis. METHOD: This
      article addresses how molecular technology can be used to aid in the diagnosis of
      this group of patients. The clinical and scientific literature is reviewed by
      accessing papers through the Medline database. RESULTS: This article reviews the
      limitations of conventional imaging techniques and the limitations of fine needle
      aspiration cytology and cytological examination of pancreatic duct secretions.
      The molecular biology of both pancreatic cancer and chronic pancreatitis is then
      reviewed with emphasis on the common molecular defects seen in these diseases.
      The current use of molecular techniques in the examination of cytological and
      histological specimens, stool, blood, and pancreatic duct secretions and how this
      helps discriminate between benign and malignant lesions of the pancreas is
      addressed. Finally, the use of novel serum screening tests in groups at high risk
      of pancreatic cancer is discussed.

PMID- 9629511
TI  - Near-infrared spectrometry analysis of fat, neutral sterols, bile acids, and
      short-chain fatty acids in the feces of patients with pancreatic maldigestion and
      malabsorption.
AB  - CONCLUSION: Near-infrared spectrometry is a new, rapid, and accurate method for
      measuring fecal fat that does not require a great deal of chemical knowledge and
      that can be used by anyone. This method is considered indispensable for the
      diagnosis of pancreatic steatorrhea and treatment follow-up. METHODS: Fecal fats
      (GLC method, van de Kamer method), neutral sterols (GLC method), bile acids (GLC
      method) and short-chain fatty acids (HPLC method) were assayed by the respective
      conventional methods in 120 subjects, including patients with pancreatic
      dysfunction, and the results were compared with the those obtained by near
      infrared spectrometry. The correlations between fecal fat excretion measured by
      the GLC method (x) and van de Kamer method (x) and by near-infrared spectrometry
      (y) were expressed by y = 1.10x - 0.16 (r = 0.949, P < 0.01) and y = 0.750x +
      1.654 (r = 0.930, p < 0.01), respectively. RESULTS: The sensitivity and
      specificity of near-infrared spectrometry for fecal fats were 94.9 and 98.2%,
      respectively, when compared with the GLC method, and 87.5 and 90.0%,
      respectively, when compared with the van de Kamer method. In contrast, near
      infrared spectrometry was not nearly as accurate as the conventional methods for
      determining neutral sterols, bile acids, and short-chain fatty acids.

PMID- 9629512
TI  - Endoscopic ductal drainage may avoid resective surgery in painful chronic
      pancreatitis without large ductal dilatation.
AB  - CONCLUSION: Endoscopic stenting treatment, in cases of chronic pancreatitis
      unsuitable for decompressive surgery, appears to be safe and efficient. Perfect
      anatomical results are only obtained if large stents are used after balloon
      dilatation. BACKGROUND: Decompressive surgery in cases of painful chronic
      pancreatitis is only feasible if the main pancreatic duct exceeds approx 8 mm
      over a sufficient length. When those anatomical changes are not present, surgery
      must be resective. This study evaluates the results of endoscopic stent drainage
      and decompression of painful chronic pancreatitis without large dilatation of the
      main pancreatic duct. METHODS: Sixteen of our chronic pancreatitis patients were
      included in this study. They presented a mean of 5.3 episodes of pain in the 6 mo
      before treatment. Decompressive surgery was not possible because of a mean
      pancreatic duct diameter of 5.8 mm. Stents were 7F in eight patients and 12F in
      the other eight. They were left in the duct after endoscopic dilation for 9.5 +/-
      1.0 mo. RESULTS: During stenting we observed two early obstructions and seven
      episodes of pain. All cysts disappeared and stenosis of the duct disappeared
      anatomically in six cases, was improved in four, but persisted in six. During
      follow-up, two episodes of mild pain were recorded. No cysts reappeared. Complete
      disappearance of stenosis was only observed in patients whose pancreatic duct was
      equipped with a 12F stent (p < 0.02).

PMID- 9629513
TI  - Carcinoid tumors of the pancreas. Status report based on two cases and review of
      the world's literature.
AB  - CONCLUSION: The diagnosis of a pancreatic carcinoid should be based on the
      measurement of serotonin in serum or its demonstration in the tumor and/or by the
      measurement of its derivative (5-HIAA) in urine. Carcinoid of the pancreas is a
      rare but definite entity; usually having metastasized by the time of diagnosis.
      The term "serotonin-producing tumor of the pancreas" has been suggested as an
      alternative designation for "pancreatic carcinoid." BACKGROUND: The literature on
      carcinoid tumors of the pancreas is confusing because much of it preceded the
      development of the more specific immunological, chemical and staining techniques
      currently available. METHODS: 43 case reports were collected from the world's
      literature, based on a demonstrable pancreatic neuroendocrine tumor plus a
      positive finding of at least one of the following without another dominant
      hormone being demonstrated: elevation of 5-Hydroxytryptamine (5-HT) (serotonin)
      in the serum or detected in tumor tissue, and/or elevation of 5-Hydroxyindole
      acetic acid (5-HIAA) in the urine. In addition to these two hormone-specific
      assays, information was collected on the silver-staining properties of the tumor;
      properties which have traditionally been associated with carcinoid tumors.
      Positive silver staining in tumor cells (argyrophilic and/or argentaffin
      reaction) is strongly indicative of the carcinoid tumor but the findings are less
      specific than the hormone assays and immunohistologic stains. RESULTS: In this
      review of 43 cases, including two current ones, the pancreatic carcinoid tumor
      has the following important features: 1. It is a rare tumor that is usually
      diagnosed late when the tumor is large and has metastasized. Thirty-eight (88.4%)
      have been malignant. They are, therefore, associated with a high incidence of the
      "carcinoid syndrome." 2. To date, prognosis in therapy is poor, based on delayed
      diagnosis, a resultant low incidence of resectability, and an uncertain duration
      of survival after resection. 3. Pancreatic carcinoid tumors remain difficult to
      differentiate from other endocrine tumors. The measurement of urinary 5-HIAA
      excretion or the demonstration of elevated serotonin level in the tumor or in
      serum is essential to its distinction. Silver staining of the tumor, although of
      historic importance, has been superceded by the hormone-specific studies. 4. To
      distinguish it from other endocrine tumors of the pancreas, the terms "pancreatic
      serotoninoma" or "serotonin-producing tumor of the pancreas" have been suggested
      as possible alternatives. Its growth characteristics may be related more to its
      cell of origin than to its extent of hormone secretion. Not all of the tumors
      result in recognizable hyperserotoninemia.

PMID- 9629514
TI  - Serous cystadenoma of the pancreas with atypical cells. Case report.
AB  - CONCLUSION: Serous cystadenomas of the pancreas may have the biologic ability to
      undergo malignant transformation. BACKGROUND: It is generally recognized that:
      serous cystadenomas of the pancreas are benign and that their malignant potential
      is low. METHODS: A serous cystadenoma of the pancreas was resected from a 53-yr
      old woman. In the central portion of the tumor, papillary structures were found
      on the cyst wall. Immunohistologic studies using antibodies to carbohydrate
      antigen 19-9, carcinoembryonic antigen, and proliferating cell nuclear antigen
      were performed to determine the malignant potential of this tumor. RESULTS: On
      histology, most tumor cells were positive for periodic acid-Schiff but were
      negative for periodic acid-Schiff after diastase digestion and Alcian blue, a
      staining pattern typical of serous cystadenomas. The cells found in the papillary
      structure of the cyst wall were mildly atypical. These cells were stained with
      antibodies to carbohydrate antigen 19-9, carcinoembryonic antigen, and
      proliferating cell nuclear antigen, indicating that the cells comprising the
      papillary structure were proliferating more rapidly than cells in other parts of
      the tumor and strongly suggesting that the cells are premalignant.

PMID- 9629515
TI  - Acute terminal pancreatitis occurring in jejunal heterotopic pancreas.
AB  - CONCLUSION: We report a unique case of acute terminal pancreatitis occurring in
      the jejunal heterotopic pancreas. Unlike previously reported cases, acute
      pancreatitis was not found histologically in the ordinary pancreas. BACKGROUND:
      Heterotopic pancreas may show the same inflammatory or neoplastic changes, such
      as acute pancreatitis and adenocarcinoma, as those that occur in the ordinary
      pancreas. However, histologically proven acute pancreatitis occurring in
      heterotopic pancreas is very rare and only three reports have been described.
      METHODS: A 53-yr-old Japanese man died of hepatic failure, and autopsy was
      performed. RESULTS: Autopsy incidentally revealed heterotopic pancreas of the
      jejunum. Microscopically, focal acute pancreatitis was observed in the jejunal
      heterotopic pancreas, whereas the pancreas of the normal location showed no
      abnormality. In addition, no clinical evidence of pancreatic disease was noted
      before death. Therefore, we diagnosed this case as acute terminal pancreatitis
      occurring in the jejunal heterotopic pancreas.

PMID- 9629516
TI  - Angiopathies in pancreatic diabetes resulting from chronic pancreatitis.
AB  - CONCLUSION: Marked diabetic micro- and macroangiopathies were recognized in three
      autopsy cases with pancreatic diabetes resulting from chronic pancreatitis.
      BACKGROUND: Recent reports have suggested that diabetic retinopathy occurs as one
      of the microangiopathies in patients with secondary diabetes following chronic
      pancreatitis. METHODS: We report three autopsy cases with pancreatic diabetes.
      Cases 1 and 2 showed alcoholic chronic pancreatitis. Case 3 was a patient with
      chronic pancreatitis resulting from hyperparathyroidism. All three cases had
      pancreatic calcification and markedly decreased exocrine pancreatic function.
      There was no family history of diabetes in these patients. The HbA1 values were
      elevated, with diminished secretion of both insulin and glucagon. RESULTS: The
      common features of the clinical courses were poor glycemic control, including
      insulin-induced hypoglycemic attacks in the early stage and microangiopathy,
      followed by difficulties in treatment for hypertension in the late stage of
      pancreatic diabetes. Autopsies, performed after 12-18 yr of diabetes, revealed
      fibrosis of the pancreas, disappearance of acinar cells in the exocrine pancreas,
      atrophy, a diminished number of islets of Langerhans, and diabetic
      glomerulosclerosis, with arteriosclerosis in the brain, heart, and kidneys.
      Cerebral hemorrhage, heart failure, and myocardial infarction were suggested to
      be the main causes of death. Although the serum lipid levels were rather low in
      cases 1 and 2, arteriosclerosis was marked by the age of 60, and serum protein
      levels were also low in all three cases.

PMID- 9629517
TI  - Celiac axis infusion chemotherapy in advanced nonresectable pancreatic cancer.
AB  - CONCLUSION: Based on these data we suggest that regional intra-arterial
      chemotherapy for advanced pancreatic cancer seems not to be superior to common
      treatment modalities, such as combined radiochemotherapy. BACKGROUND: The
      prognosis for advanced pancreatic cancer is very poor. No standard treatment is
      available. Recently, better survival and quality of life was reported from
      regional cancer treatment via celiac axis infusion. In an attempt to confirm
      these results we conducted a phase II study of intra-arterial chemotherapy for
      nonresectable pancreatic cancer. METHODS: From May 1994 to February 1995, 12
      consecutive patients with biopsy-proven advanced ductal carcinoma of the exocrine
      pancreas were given intra-arterial infusions consisting of Mitoxantrone, 5-FU +
      folinic acid, and Cisplatin via a transfemorally placed catheter in the celiac
      axis. Six patients were classified as UICC stage III and six as stage IV with the
      liver as the sole site of distant metastasis. Nine patients had primary and three
      had recurrent pancreatic carcinoma after a Whipple procedure. Nonresectability of
      primary tumors was assessed in all patients by laparotomy or laparoscopy.
      RESULTS: A total of 31 cycles of chemotherapy (mean 2.6 cycles/patient) was
      administered. Catheter placement was technically feasible in all cycles. A groin
      hematoma was the only catheter complication. The follow-up by CT scans at 2-mo
      intervals revealed partial remission in 1 patient (8%), temporary stable disease
      in 4 patients (33%), and disease progression in 7 patients (58%). The same
      response was obtained after analyzing the CA 19-9 course. Median survival in
      stage III patients was 8.5 mo (3-12 mo) and in stage IV patients 5 mo (2-11 mo).
      Toxicity according to WHO criteria consisted of grade III (4 events), grade II
      (10 events), and grade I (17 events), mainly resulting from leucopenia and
      diarrhea/vomiting. Nine of 11 patients experienced temporary relief of pain
      immediately after regional treatment.

PMID- 9629518
TI  - Prevention of hyperlipidemic acute pancreatitis during pregnancy with medium
      chain triglyceride nutritional support.
AB  - CONCLUSION: A combination of diet therapy, nutritional support with medium-chain
      triglycerides (MCT), and well-planned preterm Cesarean delivery on demand is an
      effective measure to prevent gestational hyperlipidemic pancreatitis and leads to
      successful childbirth. BACKGROUND: Prevention and therapy of gestational
      hyperlipidemic pancreatitis are important, although difficult, because the
      condition carries a high maternal and fetal morbidity and mortality. RESULTS: We
      describe a 32-yr-old female with lipoprotein lipase-deficient familial
      hypertriglyceridemia who had recurrent episodes of acute pancreatitis. The third
      episode occurred with worsened hyperlipidemia 7 yr earlier at 32 wk of her first
      pregnancy and resulted in fetal death. The fourth and fifth episodes were also
      accompanied by marked hyperlipidemia probably caused by drug discontinuance and
      dietary noncompliance. She became pregnant. Serum triglyceride levels were
      controlled below 2000 mg/dL by strict monitoring with low-fat, low-calorie diet
      and MCT nutritional support. A premature but healthy infant was born by Cesarean
      delivery at 36 wk of gestation when the mother presented with mild abdominal pain
      and was found to have uterine contractions. The ensuing clinical course has been
      uneventful.

PMID- 9629519
TI  - Apolipoprotein E and functional illness in the elderly.

PMID- 9629520
TI  - Mental health of the oldest old: the relevance of centenarian studies to
      psychogeriatric research.

PMID- 9629521
TI  - Neurochemical dissection of synaptic pathology in Alzheimer's disease.
AB  - Synaptic pathology has attained increasing attention as being central in the
      pathogenesis of Alzheimer's disease (AD). To address the question whether
      synaptic pathology in AD involves the whole synapse, or is limited to specific
      components thereof, we studied three different synaptic vesicle proteins (rab3a,
      synaptotagmin, synaptophysin) and also the presynaptic membrane protein GAP-43
      and the postsynaptic protein neurogranin. The material included postmortem brain
      tissue (frontal cortex, hippocampus, and cerebellum) from 8 patients with early
      onset AD (EAD), 11 patients with late-onset AD (LAD), 6 patients with vascular
      dementia (VAD), and 9 control subjects. A reduction of all synaptic proteins was
      found in AD, more pronounced in EAD than in LAD, in both the frontal cortex (EAD
      30% to 70% vs. LAD 82% to 88% of control value) and hippocampus (EAD 22% to 82%
      vs. LAD 76% to 89% of control value), whereas only minor changes were found in
      VAD. The finding that all synaptic proteins were reduced in AD suggests a
      degeneration and loss of whole synaptic elements that are more pronounced in EAD
      than in LAD.

PMID- 9629522
TI  - Unraveling the mystery of cognitive changes in old age: correlation of
      neuropsychological evaluation with neuropathological findings in the extreme old.
AB  - In order to understand what cognitive changes can be expected with aging versus
      those caused by disease, the New England Centenarian Study examined correlations
      between neuropsychological evaluation and neuropathological studies of
      centenarian subjects. Sixty-nine subjects were administered an extensive
      neuropsychological test battery designed for centenarians. Six brain donors from
      this group have subsequently died, and neuropathological studies of their brains
      have been performed to determine the presence of Alzheimer's disease (AD) and
      other pathological states. Of these six centenarians, three subjects had Clinical
      Dementia Rating scores of 0 and no dementia on neuropsychological testing, and
      subsequent neuropathology showed very limited AD changes. In fact, despite a
      range of neuropsychological findings, none of the subjects in this series met
      neuropathological criteria for a diagnosis of definite AD. Findings suggest that
      dementia is not inevitable with aging and that dementia in this age group is
      surprisingly often not attributable to AD.

PMID- 9629523
TI  - Adjusting Mini-Mental State Examination scores for age and educational level to
      screen for dementia: correcting bias or reducing validity?
AB  - The question of whether Mini-Mental State Examination scores should be adjusted
      for age and educational levels to screen for dementia in clinical populations is
      reexamined in the results of a recent study supporting adjustment. If the
      criterion is to identify the most accurate screening procedure for each
      sociodemographic subgroup, the evidence indicates that the unadjusted scores are
      preferable. Other criteria might lead to different conclusions. The validities of
      some of these criteria are questionable because they have the flaw that they are
      easily satisfied by using random decision procedures.

PMID- 9629524
TI  - Retrospective diagnosis of dementia using an informant interview based on the
      Brief Cognitive Rating Scale.
AB  - The accuracy of a dementia diagnosis by specialist physicians, as verified at an
      autopsy, is greater than 90% in many series. Donations of brains to the Maritime
      Brain Tissue Bank (MBTB) by individuals who did not have expert dementia
      diagnoses before death led us to investigate whether clinical features could also
      be detected retrospectively. Informants for 36 individuals whose brains were in
      the MBTB (18 women, mean age = 79 years; pathologic diagnoses: 75% Alzheimer's
      disease [AD]; 8.4% vascular or mixed dementia) were interviewed by specialist
      physicians using a semistructured retrospective interview based on the Brief
      Cognitive Rating Scale (BCRS) (range = 1 [no impairment] to 7 [terminal
      dementia]). The mean duration of dementia was 8.5 +/- 12.8 years based on proxy
      reports, and most cases suggested severe dementia--(stage 6 [severe] or 7
      [terminal])--on the retrospective BCRS (RetroBCRS) before death. A score of 4 or
      more on the RetroBCRS had 100% sensitivity and specificity in detecting dementia.
      The RetroBCRS score correlated moderately with duration (.51). In linear and
      logistic regression models adjusted for age and sex, RetroBCRS staging helped
      explain 93% of the variation in duration. The accuracy of the retrospective
      diagnosis of the cause of dementia, compared with autopsy, was 92%. The RetroBCRS
      used by an expert physician with a reliable informant is a valid method of
      detecting dementia and determining whether AD was present.

PMID- 9629525
TI  - Feasibility of retrospective assessments of behavioral symptoms in Alzheimer's
      disease: a preliminary study of postmortem caregiver reports.
AB  - Studies of the behavioral symptoms in Alzheimer's disease (AD) would be
      facilitated if reliable reports could be obtained retrospectively, especially
      about symptoms in the final months of life when concurrent assessment is often
      not feasible. To evaluate such a method, we compared results of a telephone
      interview conducted after the patient's death with information provided by the
      same informant earlier, while the patient was living. Agreement between in-life
      and retrospective assessments was higher for psychotic symptoms than for
      depressive behaviors, suggesting that retrospective assessment of specific
      behavioral symptoms in AD is not uniformly reliable. More symptoms were
      retrospectively reported as the length of time between the last in-life
      evaluation and date of death increased, suggesting that there may be increased
      variety of behavioral symptoms observed by caregivers in the final stages of the
      disease.

PMID- 9629526
TI  - Psychopathologic and functional outcome in the treatment of elderly inpatients
      with depressive disorders, dementia, delirium and psychoses.
AB  - The objectives of this report were to investigate the functional implications and
      the possible rehabilitation potentials of dementia, delirium, and psychosis in
      elderly inpatients, compared with that in depression. During 1 year, all patients
      in a psychogeriatric university clinic were assessed on admission and at
      discharge with a selection of rating scales and diagnosed according to ICD-10 by
      consultants with no knowledge of the results of the ratings. All patients who had
      a principal diagnosis of major depression, dementia, delirium, or a psychosis are
      discussed. Ratings were made for psychopathology, behavioral disorders,
      depressive statements, intellectual functioning, activities of daily living, and
      gait. Depressive and delirious patients improved their status significantly (p <
      or = .03) in all six assessments, and patients with dementia improved their
      psychopathology status (p = .002), but the other assessments were unchanged.
      Results from the small sample (n = 8) of psychotic patients were mainly
      inconclusive, but there was a tendency for improvement with respect to
      psychopathology and gait.

PMID- 9629528
TI  - Impact of geriatric home screening services on mental state: a systematic review.
AB  - The purpose of this report was to determine the impact of geriatric home
      screening services on mental state. Two computer databases, MEDLINE and
      HealthSTAR, were searched for relevant articles published from January 1975 to
      June 1997, and the bibliographies of retrieved articles were searched for
      additional references. Seven trials were located that met the four inclusion
      criteria: (a) original study; (b) published in English or French; (c) controlled
      trial (randomized or nonrandomized) of a geriatric home screening service; and
      (d) the trial included at least one measure of mental state. All trials met most
      of the validity criteria for intervention studies of the Evidence-Based Medicine
      Working Group. Two trials reported a small effect on morale or self-perceived
      health and five trials reported no effect. Thus, there was little evidence that
      geriatric home screening services had an impact on the mental state of aged
      subjects.

PMID- 9629527
TI  - Cognitive and noncognitive symptoms in dementia patients: relationship to
      cortisol and dehydroepiandrosterone.
AB  - We investigated the relationship between basal cortisol and
      dehydroepiandrosterone (DHEA) levels and impairment in different cognitive and
      noncognitive measures and the possible interaction of DHEA with hypercortisolemia
      in dementia in 27 patients diagnosed with Alzheimer's disease (AD). There were 17
      men and 10 women. Patients were mildly to moderately cognitively impaired at the
      time of the initial cortisol measures. Patients were administered the Alzheimer's
      Disease Assessment Scale (ADAS) and Folstein Mini-Mental State Examination (MMSE)
      at approximately 6-month intervals. Cortisol and DHEA were determined using
      conventional 125I radioimmunoassay procedures. Pearson product-moment
      correlations among cortisol and DHEA measures and both initial and longitudinal
      clinical measures were calculated. There was a relationship between baseline 8
      a.m. cortisol levels and cognitive function at the initial testing as measured by
      the ADAS cognitive measure, with higher cortisol levels being associated with a
      greater level of impairment. We did not document a relationship between cortisol
      or DHEA levels and noncognitive measures. There was a significant correlation
      between both the initial MMSE and ADAS cognitive measures and initial DHEA level,
      with lower DHEA levels unexpectedly being associated with better performance on
      these measures. The initial DHEA levels did not predict decline in cognitive
      function over time. These findings bring into question the potential usefulness
      of DHEA as a therapeutic agent.

PMID- 9629529
TI  - Effects of trihexyphenidyl on MMSE and CAMCOG scores of medicated elderly
      patients with schizophrenia.
AB  - The purpose of this study was to assess the effects of an anticholinergic
      (trihexyphenidyl) antiparkinsonian medication on the Mini-Mental State
      Examination (MMSE) and the Cambridge Cognitive Examination (CAMCOG) scores in
      long-term institutionalized elderly patients with schizophrenia. Seventeen
      schizophrenic (DSM-III-R) inpatients on long-term medication who had received
      trihexyphenidyl for at least 6 consecutive months were compared for MMSE scores,
      CAMCOG scores, and other demographic and clinical variables with 14 patients not
      receiving any anticholinergic agent for the same time period. Results showed that
      age, years of education, illness duration, length of current hospital stay, the
      Manchester Scale scores, and chlorpromazine daily equivalent dose in mg were not
      different in the two groups compared. Extrapyramidal signs such as tremor,
      rigidity, and bradykinesia were more frequent in trihexyphenidyl receivers. The
      scores of MMSE (p < .007) and CAMCOG (p < .005) and CAMCOG subscales of
      orientation (p < .03), language (p < .01), and memory (p < .002) were
      significantly lower among trihexyphenidyl receivers, as was the Social and
      Occupational Functioning Assessment Scale score (p < .05). In addition, the MMSE
      and CAMCOG scores were significantly lower for patients receiving 10 mg of
      trihexyphenidyl a day compared with those receiving 5 mg/day and nonusers. It is
      suggested that trihexyphenidyl in usual clinical doses may impair total MMSE and
      CAMCOG scores as well as some of the CAMCOG subscales in this patient population.
      However, only a prospective study, preferably double-blind and controlled, with
      measures of change will validate this conclusion.

PMID- 9629530
TI  - Matrix metalloproteinase inhibitors in arthritis.

PMID- 9629531
TI  - Carbonic anhydrase inhibitors: ureido and thioureido derivatives of aromatic
      sulfonamides possessing increased affinities for isozyme I. A novel route to 2,5
      disubstituted-1,3,4-thiadiazoles via thioureas, and their interaction with
      isozymes I, II and IV.
AB  - Reaction of 12 aromatic sulfonamides containing a free amino group with cyanate
      or thiocyanate in the presence of acid afforded the corresponding urea/thiourea
      derivatives which were assayed as inhibitors of three isozymes of carbonic
      anhydrase (CA), i.e., CA I, II and IV. Oxidation of the obtained thioureas with
      iodine in acidic medium afforded symmetrical 2,5-bis(substituted-phenyl)-1,3,4
      thiadiazole derivatives possessing sulfonamido groups on the aromatic ring, via a
      new synthesis of the heterocyclic moiety. Good inhibition of all these three CA
      isozymes was observed with the new compounds, but a novel finding was that the
      ureas/thioureas reported here had an increased affinity for the slow isozyme CA
      I, which generally is less sensitive to inhibition by sulfonamides when compared
      to the rapid isozymes CA II and IV. The disubstituted-1,3,4-thiadiazoles on the
      other hand were better inhibitors of CA II than CA IV and especially CA I,
      similarly to the large majority of aromatic/heterocyclic sulfonamides. Some of
      the new compounds could constitute good lead molecules for developing more
      selective CA I inhibitors.

PMID- 9629532
TI  - Inhibitors of the epidermal growth factor receptor protein tyrosine kinase: a
      quantitative structure-activity relationship analysis.
AB  - Hansch and Free-Wilson analyses are described on a data set, 4
      anilinoquinazolines [the analogues of 4-(3-bromo-anilino)-6,7-dimethoxy
      quinazoline: PD 153035], as inhibitors of the epidermal growth factor receptor
      protein tyrosine kinase. These analyses have helped to ascertain the role of
      different substituents in explaining the observed inhibitory activities. From
      both approaches, it is concluded that the combined electron-donating nature of R1
      and R2-substitutions of the quinazoline ring and the electron-withdrawing nature
      of the X-substitution of the anilino-ring are beneficial for increasing the
      inhibition activity of a compound. Further, the symmetrical alkoxy substituents
      present at the R1- and R2-positions are also engaged in a steric interaction
      which was determined quantitatively through the parabolic relationship between
      the activity and combined molar refraction parameter, sigma MR of the
      substituents.

PMID- 9629533
TI  - 1513-DMIa and 1513-DMIb, DNA methyltransferase inhibitors produced by
      Streptomyces sp. strain No. 1513.
AB  - Two new methyltransferase inhibitors were isolated from the culture filtrate of
      Streptomyces sp. strain No. 1513 and named 1513-DMIa and 1513-DMIb. 1513-DMIa and
      1513-DMIb were distinguished in certain properties from DMI-1, DMI-2, DMI-3 and
      DMI-4 previously reported. The molecular weight of 1513-DMIa and 1513-DMIb were
      estimated to be 576 and 8400 from the results of FAB-MS and gel filtration,
      respectively. The inhibitory activities of 1513-DMIa and 1513-DMIb were shown to
      be pH- and temperature-dependent and both inhibited M. EcoRI in an uncompetitive
      manner with respect to DNA or S-adenosylmethionine (SAM).

PMID- 9629534
TI  - Studies on the inactivation of Leuconostoc mesenteroides NRRL B-512F
      dextransucrase by o-phthalaldehyde: evidence for the presence of an essential
      lysine residue at the active site.
AB  - The kinetics of inactivation of Leuconostoc mesenteroides NRRL B-512F
      dextransucrase by o-phthalaldehyde showed that the reaction followed pseudo-first
      order reaction. The loss of enzyme activity was concomitant with an increase in
      fluorescence at 417 nm indicating that the inhibition involved the reaction of an
      epsilon-amino and a thiol group of the enzyme leading to the formation of an
      isoindole derivative. The stoichiometry of inactivation showed that one isoindole
      derivative was formed per enzyme molecule. The substrates sucrose and glucose
      provided protection against o-phthalaldehyde inactivation which was also
      corroborated by fluorescence studies. Dextransucrase was not inactivated by 5,5'
      dithiobis(2-nitrobenzoic acid), showing that the cysteine present in close
      proximity to the lysine is not essential for enzyme activity. Denaturation of
      dextransucrase by urea or heat treatment prior to o-phthalaldehyde addition
      resulted in a decrease of fluorescence intensity indicating that the native
      conformation of the enzyme is essential for isoindole derivative formation. These
      results established that a lysine residue is present at the active site and is
      essential for the activity of dextransucrase.

PMID- 9629535
TI  - Equations for progress curves of some kinetic models of enzyme-single substrate
      single slow binding modifier system.
AB  - A procedure is described by means of which the equations for progress curves for
      the kinetic models that include fast and slow reaction steps can be derived. It
      is based on combined assumptions of equilibrium and steady-state and uses Laplace
      transformation for solving the systems of differential equations. The progress
      curve equations and the significance of the corresponding parameters are given
      for some most frequently occurring models describing the influence of a slow
      binding modifier on a single substrate enzyme reaction.

PMID- 9629536
TI  - Carbonic anhydrase inhibitors: inhibition of isozymes I, II and IV with
      heterocyclic mercaptans, sulfenamides, sulfonamides and their metal complexes.
AB  - A series of sulfenamides, sulfonamides and sulfonamide metal complexes have been
      prepared starting from 4,5-disubstituted-3-mercapto-1,2,4-triazole derivatives.
      The heterocyclic mercaptans were oxidized to the corresponding sulfenamides by
      hypochlorite in the presence of ammonia. The sulfonamides were obtained by
      oxidation of sulfenamides with potassium permanganate. The Zn(II) and Cu(II)
      complexes of the new heterocyclic sulfonamides have been prepared via the sodium
      salt of the ligand. Inhibition of three carbonic anhydrase (CA) isozymes, hCA I,
      hCA II and bCA IV (h = human, b = bovine) with the prepared compounds has been
      investigated. Mercaptans were generally less inhibitory than sulfenamides, which
      in turn behaved as weaker inhibitors than the sulfonamides. The strongest
      inhibitors were the Zn(II) and Cu(II) complexes of the heterocyclic sulfonamides.
      Susceptibility to inhibition was generally: hCA II > bCA IV > hCA I. Although
      none of the obtained simple inhibitors (mercaptans, sulfenamides, sulfonamides)
      possessed antiglaucoma action when administered directly into the eye in
      experimental animals, the Zn(II) and Cu(II) complexes of some sulfonamides acted
      as more efficient intraocular pressure lowering agents as compared to the
      clinical drug dorzolamide. This constitutes an encouraging result for obtaining
      novel antiglaucoma drugs from this class of CA inhibitors.

PMID- 9629537
TI  - A beta-lactam inhibitor of cytosolic phospholipase A2 which acts in a
      competitive, reversible manner at the lipid/water interface.
AB  - Cytosolic phospholipase A2 (cPLA2) catalyzes the selective release of arachidonic
      acid from the sn-2 position of phospholipids and is believed to play a key
      cellular role in the generation of arachidonic acid. When assaying the human
      recombinant cPLA2 using membranes isolated from [3H]arachidonate-labeled U937
      cells as substrate, 3,3-Dimethyl-6-(3-lauroylureido)-7-oxo-4-thia-1
      azabicyclo[3,2,0] heptane-2-carboxylic acid (1) was found to inhibit the enzyme
      in a dose-dependent manner (IC50 = 72 microM). This beta-lactam did not inhibit
      other phospholipases, including the human nonpancreatic secreted phospholipase
      A2. The inhibition of cPLA2 was found not to be time-dependent. This, along with
      the observation that the degradation of the inhibitor was not catalyzed by the
      enzyme, demonstrates that the inhibition does not result from the formation of an
      acyl-enzyme intermediate with the active site serine residue. Moreover, the ring
      opened form of 1 is also able to inhibit cPLA2 with near-equal potency. To
      further characterize the mechanism of inhibition, an assay in which the enzyme is
      bound to vesicles of 1,2-dimyristoyl-sn-glycero-3-phosphomethanol containing 6-10
      mole percent of 1-palmitoyl-2-[1-14C]-arachidonoyl-sn-glycero-3-phosphocholine
      was employed. With this substrate system, the dose-dependent inhibition was
      defined by kinetic equations describing competitive inhibition at the lipid/water
      interface. The apparent dissociation constant for the inhibitor bound to the
      enzyme at the interface (KI*app) was determined to be 0.5 +/- 0.1 mole% versus an
      apparent dissociation constant for the arachidonate-containing phospholipid of
      0.4 +/- 0.1 mole%. Thus, 1 represents a novel structural class of inhibitors of
      cPLA2 which partitions into the phospholipid bilayer and competes with the
      phospholipid substrate for the active site.

PMID- 9629538
TI  - Inhibitory effect of 1,3,5-triphenyl-4,5-dihydro-(1H)-pyrazole derivatives on
      activity of amine oxidases.
AB  - A new series of 1,3,5-triphenyl-4,5-dihydro-(1H)-pyrazole derivatives was
      synthesized to ascertain the contribution of substituted phenyl rings present on
      the 4,5-dihydro-(1H)-pyrazole nucleus to the monoamine oxidases inhibition and
      bovine serum amine oxidase inhibition. All compounds were tested on bovine brain
      mitochondria preparation containing flavin-monoamine oxidases and on purified
      bovine serum amine oxidases, taken as a model of trihydroxyphenylalanine quinone
      copper-containing amine oxidases. The 1,3,5-triphenyl-4,5-dihydro-(1H)-pyrazole
      derivatives showed a good inhibitory activity and belonged to the third
      generation of monoamine oxidase inhibitors and bovine serum amine oxidase
      inhibitors which have the advantage of acting through a reversible mode.
      Furthermore, their activity showed a good degree of selectivity towards the
      bovine serum amine oxidase inhibition dependent on the substituents present on
      the phenyl ring at position 5 of the 4,5-dihydro-(1H)-pyrazole.

PMID- 9629539
TI  - Inactivation of enoyl-CoA reductase in pigeon liver fatty acid synthetase by
      pyridoxal 5'-phosphate: evidence for the presence of one lysine residue at the
      active site.
AB  - Pigeon liver fatty acid synthetase (FAS) was rapidly inactivated by pyridoxal 5'
      phosphate (PLP). Assays of the partial activities of the PLP-treated synthetase
      showed that only the enoyl-CoA reductase was decreased significantly. The
      inactivation of both the overall activity and enoyl-CoA reductase activity of FAS
      by PLP could be reversed by dialysis or dilution but not by reduction with sodium
      borohydride. Malonyl-CoA and acetyl-CoA did not protect the enzyme, whereas NADPH
      provided 68% protection against PLP-inactivation indicating that PLP modified
      lysine residues present at or near the co-enzyme binding site. PLP-treated enzyme
      after reduction with sodium borohydride exhibited fluorescence with a maximum at
      397 nm (irradiation at 325 nm). Stoichiometric analysis showed that modification
      of four lysine residues per enzyme molecule resulted in complete inactivation of
      the overall and enoyl-CoA reductase activities of FAS. NADPH prevented the
      inactivation by protecting two of these lysine residues from modification,
      suggesting the presence of two essential lysine residues per enzyme molecule.
      These results are consistent with the hypothesis that each subunit of the enzyme
      contains an enoyl-CoA reductase domain in which a lysine residue, at or near the
      active site, interacts with NADPH.

PMID- 9629540
TI  - Inhibition of camel lens zeta-crystallin/NADPH: quinone oxidoreductase activity
      by chlorophenols.
AB  - Chlorophenols comprise a major class of environmental contaminants. They are
      extensively used as insecticides, fungicides, mold inhibitors, antiseptics and
      disinfectants. We found some of these compounds to be strong inhibitors of zeta
      crystallin. This oxidoreductase enzyme was isolated from camel lens and its
      enzymatic activity was inhibited by the chlorophenols tested in a time
      independent but concentration-dependent manner. 2,4,5-Trichlorophenol was the
      most potent inhibitor (IC50 = 3 microM; Ki = 3.2 microM) whereas 4-chlorophenol
      was the least potent (IC50 = 4.1 mM). There appeared to be a relationship between
      the degree of chlorination of the phenols and inhibition of zeta-crystallin
      activity. The position of the chlorine substituent on the phenol may also
      influence the potency of these compounds.

PMID- 9629541
TI  - Melanotic neuroectodermal tumor of infancy.
AB  - A 6-month-old female presented with a swelling of the left superior maxillary
      bone. A radiograph revealed a radiolucent lesion in the left anterior maxilla,
      and CT, showed a solid mass. At surgery, the lesion was a cystic dental tumor of
      ectopic location which was treated by excision. The pathological diagnosis was
      melanotic neurorectodermal tumor. This is an uncommon benign tumor of the neural
      crest origin that occurs mainly in the maxilla (70% of cases) but can occur in
      other areas such as the skull and the mandible. CT reveals a hyperdense mass and
      MR shows a hypointense mass on T1-weighted images and an iso-intense mass on T2
      weighted images. The evolution is usually benign after surgical removal.

PMID- 9629542
TI  - [Heparin-induced type II thrombocytopenia within the scope of high dose
      chemotherapy with subsequent stem cell rescue].
AB  - We report on a 17-year-old young man with rhabdomyosarcoma in the right parotid
      area. Relapse therapy was performed with high dose chemotherapy and consecutive
      autologous stem cell rescue. During this therapy heparin-induced thrombocytopenia
      was diagnosed. Because of its proven antithrombotic activity Danaparoid-Sodium, a
      natural low molecular glycosaminoglycan preparation, was used for further
      antithrombotic prophylaxis. We discharged our patient from the laminar air flow
      unit six months ago. The alternative antithrombotic therapy was tolerated without
      any problems. No bleeding events occurred, thrombotic complications and veno
      occlusive disease of the liver were avoided.

PMID- 9629543
TI  - [Progress in prevention and therapy of infectious complications in children and
      adolescents with neoplastic diseases].
AB  - Due to the high dose-intensity of most current treatment protocols, the growing
      number of marrow transplantations, the routine use of aggressive supportive care
      and certain pathogen-related problems, infections remain an important cause for
      morbidity and mortality in children and adolescents with cancer. Over the last
      decade, however, considerable progress has been made in diagnosis, prevention and
      treatment of infectious complications in the immunocompromised host. This article
      first delineates both clinical approach and current treatment strategies in the
      pediatric cancer patient presenting with neutropenia and fever of unknown origin.
      It then reviews diagnosis and treatment of the most common specific infections
      and concludes with a discussion of preventive measures in the setting of
      anticancer treatment.

PMID- 9629544
TI  - [Effect of birth weight on hip maturation in the newborn infant].
AB  - In 2018 consecutive newborn ultrasound examination of the hip was performed
      according to the method of Graf within the first 14 days of life (average 4th
      day). Typ IIa was seen as normal in newborn child. Birth weight was classified
      according to standards of Lubchenco and Hohenauer. Newborn with high birth weight
      (LGA) revealed an incidence of CDH (Typ IIc according to Graf or worse) nearly
      twice as high as in normal weighted newborn (AGA) (6.11% vs 3.51% [Lubchenco] and
      7.95 vs 3.09 [Hohenauer]). Even in children with birth weight between 75th and
      90th percentile we found a CDH incidence of 5.54%. Ultrasound examination of the
      hip is suggested in newborn children with high birth weight because of a higher
      risk for development of a CDH. Other risk-factors like breech position or of CDH.

PMID- 9629545
TI  - [Spontaneous subdural hematoma in a 18-day-old male newborn infant with severe
      hemophilia A].
AB  - Most intracranial bleedings in hemophiliacs occur in patients more than 6 months
      of age. In the neonatal period, this complication is rare and almost always
      observed in the first week of life. Based on a review of the literature,
      intracranial hemorrhage is an exceedingly rare occurrence in infants with
      hemophilia aged 2 weeks-6 months. We report on a male infant with hemophilia A
      who was referred to our hospital on day 18 because of pallor and jaundice. The
      neurological examination was normal. A cerebral ultrasound showed a left sided
      subdural hematoma with a shift of the midline structures to the right. Packed red
      blood cells (10 ml/kg) and factor VIII replacement (250 IU) were rapidly
      instituted and a craniotomy with evacuation of the hematoma was performed. The
      postoperative course was uneventful. On discharge, the neurological examination
      was considered normal.

PMID- 9629546
TI  - [Acquired toxoplasmosis with cerebral involvement and subsequent hearing loss].
AB  - In immunocompetent patients the postnatally acquired toxoplasmosis is usually a
      mild or asymptomatic disease. CNS manifestations are rare, e.g. in patients with
      HIV infection or in patients with other types of immunosuppression. We report on
      a 9-year old healthy boy, who was hospitalized after one week with subfebrile
      temperatures and headache with clinical signs of encephalitis and unilateral
      deafness. We diagnosed a toxoplasmosis and treated the patient with pyrimethamine
      and sulfadiazine. While most of the signs and symptoms disappeared rapidly the
      deafness persisted.

PMID- 9629548
TI  - [Tuberculous meningitis in a 13-month-old boy: a case report].
AB  - We present the case of a 13-month old Turkish boy of Kurdish origin with
      tuberculous meningitis. Fever of unknown origin and neurologic symptoms (loss of
      ability of walking and free sitting, cerebral seizures, central paresis of the
      VII. cranial nerve, coma) led to the diagnosis. Cranial CT demonstrated
      hydrocephalus and enhancement of the basal meninges after contrast injection; the
      chest x-ray showed an infiltrate in the right upper lobe of the lung and the
      cerebrospinal fluid (CSF) mild pleocytosis with elevated protein and reduced
      glucose concentrations. Diagnosis was confirmed by detection of Mycobacterium
      tuberculosis in the CSF by polymerase chain reaction (PCR). Immediately, surgical
      and level-controlled tuberculostatic treatment was initiated. The patient
      recovered completely.

PMID- 9629547
TI  - [Toxocariasis in a 5-year-old boy--manifesting as bronchial asthma and behavioral
      disorder].
AB  - We report on a five year old boy who was admitted to hospital because of
      obstructive airway disease; initially, findings were interpreted to indicate
      bronchial asthma. In addition, the patient presented with a behavioural
      abnormality of aggressiveness and hyperactivity. Laboratory examinations showed
      an elevated IgE level and eosinophilia, chest x-ray revealed infiltrations in
      both lungs. After excluding a spectrum of chronic lung disorders by relevant
      investigations, serological testing for parasitosis revealed massively elevated
      toxocara IgG antibodies. The diagnosis of a "covert form" of toxocarosis was
      established and an antihelminthic therapy with albendazole was initiated. Chronic
      respiratory symptoms in childhood can also indicate the presence of a parasitic
      infestation.

PMID- 9629549
TI  - [Azathioprine ingestion with suicidal intent by an adolescent with chronic
      juvenile polyarthritis].
AB  - We report on a 13 years 7 months old boy who ingested 650 mg azathioprine in a
      suicide attempt. His baseline medication was azathioprine and methotrexate for
      control of juvenile chronic polyarthritis. After the induction of vomiting by
      ipecacuanha sirup and administration of charcoal (1 g/kg), he was closely
      followed for haematological, hepatic, and renal side effects. During the
      following days, no serious adverse events were noted except that the thrombocyte
      (from 403,000 down to 199,000/microliter) and total leukocyte count decreased
      moderately (from 12,000 down to 7100/microliter). On the basis of this case
      report and the available literature, the potential acute toxicity of azathioprine
      and possible treatment modalities are discussed.

PMID- 9629550
TI  - [Toxocariasis--a neglected ubiquitous helminthiasis in children and adolescents].
AB  - More than 40 years ago, Toxocara ssp. was identified as the cause of larva
      migrans visceralis and ocular larva migrans, which mainly affect infants and
      children. Although widespread in most parts of the world, the parasitic disease
      is rarely diagnosed in Germany. Focusing on clinical and pathophysiological
      similarities with allergic asthma of childhood, the main epidemiological,
      clinical, therapeutical, and pathophysiological aspects of toxocariasis will be
      reviewed in the following survey.

PMID- 9629552
TI  - [Normal and pathological cognitive aging].
AB  - The relation of age associated changes of cognitive functions to those of
      dementia diseases is not well investigated for very old age. Because aging as
      well as dementia diseases are associated with cognitive deficits, this leads to
      differential diagnostic problems in very old age. Relevant with respect to this
      differentiation are on the one hand the concepts of cognitive ageing, the
      dementia syndrome and dementia diseases, and on the other hand empirical findings
      with respect to 1. the neuropsychological crossectional pattern, 2. the premorbid
      intelligence or adult intelligence level, 3. the speed of decline. ad 1. The
      speed of cognitive processes shows a considerable reduction in normal aging.
      However, the reduction of learning and orientation as well as pronounced word
      finding problems seem to be characteristic of the development of a dementia
      syndrome. ad 2. The importance of the level of adult intelligence is demonstrated
      by the possibility that a very old person with low adult intelligence level is
      diagnosed as demented without suffering from one of the dementia diseases. In the
      opposite case of a slowly progressive dementia disease in a person with a
      superior level of adult intelligence a diagnosis of dementia according the
      standard criteria can be given only in an advanced stage of the disease. ad 3.
      The importance of the speed of decline of cognitive performance for the diagnosis
      of dementia is discussed (e.g. < 1 point of the MMSE vs > 3 MMSE points per
      year). An optimization of the time course criterion (change-sensitive tests and
      an empirically determined cut-off) could improve the early dementia diagnosis,
      which relies up to now mostly on crossectional features. The more precise
      assessment of the deterioration speed would be an opportunity to investigate the
      factors or processes which determine the deterioration speed, knowledge of which
      in turn would be a starting point for development of therapy.

PMID- 9629551
TI  - [Recommendations for treatment of amebiasis. German Society of Pediatric
      Infectiology e.V. (DGPI), "Parasitology" Working Group].

PMID- 9629553
TI  - [Tau protein. A potential biological indicator for early detection of Alzheimer
      disease].
AB  - In 40 patients with Alzheimer's disease (AD), in 5 patients with non-AD dementia
      and in 36 cognitively normal controls the concentration of protein tau was
      determined in the cerebrospinal fluid (CSF). Of the AD patients, 19 were very
      mildly demented (MMSE score from 25 to 28). Even in these patients, CSF tau was
      significantly more elevated than in controls. In the non-AD patients protein tau
      was less increased. Among the AD patients there was no association between CSF
      tau and severity of cognitive impairment or deficit in cerebral blood flow,
      determined by SPECT. Our findings suggest that CSF tau may be elevated even at
      the predementia stage of AD and be useful as a biological marker for the early
      recognition of the disease.

PMID- 9629554
TI  - [Explaining and understanding in psychiatry].
AB  - The philosophical debate on explanation and understanding also led to basic
      methodological reflections in psychiatry. Subsuming one fact under a general law
      is the characteristic feature of scientific explanations. In this way, deductive
      conclusions can be achieved with a high degree of objectivity. Hermeneutical
      understanding makes way for interpretations in front of a given theoretical
      matrix. On the other hand, sympathetic understanding is a matter of conceiving
      single-part items as a consequence of other singular aspects (e.g., tracing back
      an action to an intention). If one understands the growth of knowledge as a
      rational and critical process, it seems no more justified to insist on exclusive
      methodologically based positions.

PMID- 9629555
TI  - [Delusions and intuition].
AB  - Taking into account the different concepts of delusion and analysing rational and
      intuitive cognition, the present phenomenological-conceptual study aims at
      defining the essential nature of delusion. Intuitive cognition as a result of
      holistic processing is founded in the development of polysensoric-kinaesthetic
      basic pictures (eidetic matrices), which are recognized preverbally and
      prereflexively by subliminal perception of corresponding eidetic structures. A
      positive match between a matrix and a given phenomenon produces an eidetic
      feeling. This eidetic feeling encompasses three aspects. The first is a preverbal
      knowledge of something as something definite. As a direct self-reference, the
      second is the feeling of an object-inherent significance of the given phenomenon
      for the subject itself. Thirdly, a power vector is perceived to derive from the
      object. The application of this concept allows us to consider delusion as a
      disturbance in the system of holistic information processing. This disturbance is
      characterized by a disinhibition and actualization of eidetic matrices in
      different ways. The resulting eidetic feeling we call delusion; its expression in
      thoughts and words we call a delusional idea. All features of an eidetic feeling
      can be demonstrated in delusion. Owing to their special intensity and suspended
      reason, they mostly appear to be unique. The analysis of the eidetic structures
      of delusion allows a deeper understanding of delusion and facilitates both its
      diagnosis and its differentiation. Heterogeneous terms, such as delusional mood,
      idea of meaning, idea of reference, delusional notion and delusional perception
      emerge in an understandable context.

PMID- 9629556
TI  - [Artifactual disorders--between deception and self-mutilation. Experiences in
      consultation psychiatry at a university clinic].
AB  - During a 18-year-period 93 patients (f = 76, m = 17) with a factitious disorder
      were identified in the psychiatric consultation service of a university hospital
      (incidence: 0.62%). 50% of women were working in medical professions whereas only
      6% of men. Chronic courses of illness were prevailing, but at least one quarter
      of female patients showed an intermittent type. There was a classical Munchhausen
      syndrome in 11% of patients. Depressive and anxiety disorders (10%, 4%) were to
      be respected as psychiatric comorbidity. Ca 25% of the patients suffered from a
      somatic illness in addition to the factitious disorder, and one third of the
      women had symptoms of psychosomatic, especially of eating disorders. Previous
      somatoform disorders, deliberate self harm and attempts of suicide were to be
      noted in the psychiatric history of many patients. There were frequent
      traumatizing events (foster home, disturbing family disharmony, physical and
      sexual abuse, early losses, serious illnesses) in the early biography. Various
      psychosocial stressors could be identified in the actual eliciting situation. The
      results are discussed in respect of epidemiology, development and clinical
      phenomenology of factitious disorders, psychodynamics and psychopathology of
      deception and self harm, and therapeutic options in the psychiatric consultation
      service.

PMID- 9629557
TI  - [Experimental detection of inadequate affect regulation in patients with self
      mutilating behavior].
AB  - According to DSM-IV affective instability in borderline personality disorder is
      due to marked reactions to environmental events. The aim of this study was to
      investigate affective responsiveness of abnormal personalities with self-harming
      impulsive behaviors by means of an affect-stimulation design. The first
      experiment was based on the presentation of a short story that allowed affective
      responses to various stimuli to be assessed in regard to quality, intensity, and
      alterations over time. The second one presented a typical frustration design,
      which provoked specific feelings of anger and disappointment. Impulsive
      personalities showed an affective hyperreactivity that was characterized by a
      decreased threshold for affective responses, as well as by intensive, rapidly
      changing affects. Furthermore, affect experiences turned out to be qualitatively
      diffuse and undifferentiated. Results support that affective instability of
      patients with borderline personality disorder should be differentiated from the
      autonomous deviations of mood typical of affective disorders. Their affective
      hyperreactivity is a crucial part of impulsive personality functioning.

PMID- 9629558
TI  - [Male anorexia nervosa patients in long-term follow-up].
AB  - Despite an increasing number of studies on the long-term course of anorexia
      nervosa, male patients only play a subordinate role in the majority of
      investigations. Thus, one section of a more comprehensive study aimed at
      describing possible differences in the disease course of male and female
      patients. Total assessment after a mean of 12 years revealed a clearly increased
      mortality rate of more than 20% in 10 of the male patients examined (as well as 2
      male anorexia nervosa patients with an additional physical condition). The male
      survivors had a better prognosis than the females patients. Male anorectics were
      in better physical condition than their female counterparts at the time of follow
      up. On the Morgan Russell scale, food intake, psychosexual and social state
      showed a more favorable development in male than in female patients. Male
      patients had a more favorable course regarding psychosocial integration but a
      similar course as female patients regarding eating disorder symptoms. The results
      are discussed theoretically and clinically. Further studies with a larger random
      selection of patients should be carried out.

PMID- 9629559
TI  - [How effective and acceptable is a self-treatment manual with concomitant brief
      therapy in bulimia nervosa].
AB  - We compared 8 fortnightly sessions plus a self-care manual (guided self change,
      GSC) with 16 weekly individual sessions of cognitive behaviour therapy (CBT).
      There were 31 sufferers of DSM-III-R-bulimia nervosa (BN) in each group. Both
      treatments resulted in significant improvements regarding self and interviewer
      based measures of bulimia nervosa as well as depression, self-esteem, quality of
      life and knowledge about nutrition, weight and shape. There were no significant
      differences between therapies regarding drop-out rate, compliance with follow-up,
      and the number of patients receiving additional treatment. At none of the
      assessments was there a significant difference between GSC and CBT regarding
      severity of BN, Beck Depression Inventory-score, self-esteem, and quality of
      life. A significantly higher percentage of CBT-patients were abstinent from
      bingeing for at least one week at the end of treatment. Three months later, the
      GSC-group had caught up in this respect and knew more about nutition, weight and
      shape. Only the sum-scores on a BN self-rating scale were worse for GSC than CBT
      at the end of therapy and at follow-up. There were no significant differences
      between the two groups in general treatment satisfaction and judgement about the
      usefulness of the therapies. Thus, guided self change with a selfcare manual can
      save therapist time without impinging significantly on treatment satisfaction and
      effectiveness.

PMID- 9629560
TI  - [The young Heine. Case history of pseudologia phantastica].
AB  - The young Heinrich Heine showed signs of pseudologia phantastica. While studying
      the diaries of his greatuncle, he identified with the latter. The underlying
      factors of this psychopathological development are discussed in this paper.

PMID- 9629561
TI  - [Differential diagnosis of dissociative identity disorder (multiple personality
      disorder)].
AB  - Recently the concept of dissociative identity disorder (formerly known as
      multiple personality disorder) has attracted increasing public and scientific
      interest. However, it is rarely diagnosed in the clinical setting. the reported
      case of a 47-year-old woman with a history of child abuse demonstrates the
      problems of differential diagnosis. A number of psychopathologic symptoms pointed
      to a multiple personality disorder, but in the follow-up psychotic symptoms such
      as delusions, possible hallucinations and bizarre behavior clearly emerged. The
      differential diagnosis of dissociative identity disorder includes paranoid
      schizophrenia, as in the case described, borderline personality disorder,
      hysteria, simulation and the false memory syndrome. Finally, social and cultural
      factors have to be considered.

PMID- 9629562
TI  - [Dysmorphophobia. Becoming estranged with oneself as a disorder of
      communication].
AB  - Dysmorphophobia shall be described as an example for a communicative disorder and
      be deliminated from other syndromes under which it has been subsumed so far. On
      the background of available literature, the "fear of deformity" is to be
      elaborated as feeling ashamed of the contemptuous look of another person, whose
      look has turned into the own view. This results in a discrepancy with the ego and
      the own self conveyed by others, finally leading to depersonalisation. This basic
      interpersonal appearance shall be further illustrated by two individual examples.

PMID- 9629563
TI  - [Psychodynamics and therapy of trichotillomania].
AB  - After a short review of the literature, some aspects of the psychodynamics and
      therapy of trichotillomania with an adolescent patient are presented that up to
      now have not been described in great detail. Against the backdrop of previous
      fears of being abandoned, the patient feels threatened that while coping with the
      developmental tasks of sexuality and aggressiveness she will be dropped once
      again. This psychodynamically oriented therapy makes it possible for the patient
      to accept and verbalize the corresponding feelings in a relationship that gives a
      feeling of security. Therefore, the symptoms that previously served the purpose
      of regulating diffuse inner tensions and fears may be abandoned.

PMID- 9629564
TI  - Subchronic phencyclidine administration increases mesolimbic dopaminergic system
      responsivity and augments stress- and psychostimulant-induced hyperlocomotion.
AB  - Previous studies have shown that repeated exposures to phencyclidine (PCP)
      induces prefrontal cortical dopaminergic and cognitive deficits in rats and
      monkeys, producing a possible model of schizophrenic frontal cortical
      dysfunction. In the current study, the effects of subchronic PCP exposure on
      forebrain dopaminergic function and behavior were further explored. Prefrontal
      cortical dopamine utilization was reduced 3 weeks after subchronic PCP
      administration, and the cortical dopaminergic deficit was mimicked by repeated
      dizocilpine exposure. In contrast, stress- and amphetamine-induced
      hyperlocomotion, behavior believed to be mediated by activation of mesolimbic
      dopamine transmission, was enhanced after PCP exposures. Furthermore, haloperidol
      induced increases in nucleus accumbens dopamine utilization were larger in
      magnitude in PCP-treated rats relative to control subjects. These data are the
      first to demonstrate that repeated exposures to PCP causes prefrontal cortical
      dopaminergic hypoactivity and subcortical dopaminergic hyper-responsivity in
      rats, perhaps mimicking alterations in dopaminergic transmission that underlie
      the behavioral pathology of schizophrenia.

PMID- 9629565
TI  - Effects of clozapine on in vitro immune parameters: a longitudinal study in
      clozapine-treated schizophrenic patients.
AB  - Clozapine is an atypical antipsychotic agent with immunomodulatory properties. We
      hypothesized that in vitro immune parameters of peripheral blood mononuclear
      cells (PBMC) are affected in the course of clozapine treatment and that clozapine
      per se, added in vitro to PBMC cultures of clozapine-treated patients, exerts
      differential effects in the timecourse of treatment in vivo. We measured
      proliferation and cytokine secretion of PBMC, serum autoantibodies, and
      immunoglobulin levels in 17 patients before and during the first 6 weeks of
      clozapine treatment. Independent of clozapine dosage and rectal temperature,
      clozapine treatment in vivo suppressed proliferation and shedding of sIL-2r by
      PBMC, and the addition of clozapine in vitro induced, relative to unstimulated
      conditions, PBMC proliferation and secretion of IL-6 and sIL-2r. Serum IgG levels
      were increased; whereas, autoantibody pattern was unaffected. Thus, clozapine
      treatment and the addition of clozapine in vitro exert differential effects on
      various in vitro immune parameters independent of clozapine dosage and rectal
      temperature in the course of treatment.

PMID- 9629566
TI  - Serotonin subtype 2 receptor genes and clinical response to clozapine in
      schizophrenia patients.
AB  - Using a pharmacogenetic approach in 185 schizophrenics who have been
      prospectively assessed for clozapine response, we have examined the hypothesis
      that polymorphisms in the 5-HT2A (HTR2A), and 5-HT2C (HTR2C) genes are involved
      in its variable response. A-1438 A-->G polymorphism in the putative promoter and
      a silent T-->C 102 substitution in HTR2A were in almost complete linkage
      disequilibrium, and neither was associated with response (T-->C. 102 allele: chi
      2 = 0.02; 1 df, p = .90; genotype: chi 2 = 0.02, 2 df, p = .99). A his452tyr
      HTR2A polymorphism was found to be associated with clozapine response (his452tyr
      allele: chi 2 = 6.43, 1 df, p = .01 [p = .04, Bonferroni corrected]; genotype:
      chi 2 = 6.54, 2 df, p = .04 [p = .16, Bonferroni corrected]). No HTR2A haplotype
      was associated with response. Interethnic differences were observed in the
      frequencies of the cys23ser HTR2C polymorphism. This polymorphism was not
      significantly associated with response in either of the ethnic groups (Caucasian
      and African American genotype: chi 2 = 3.46, 2 df, p = .18; chi 2 = .31, 2 df, p
      = .86, respectively). Although replication is required, the overall results
      suggest that the his452tyr HTR2A polymorphism may be involved in clozapine
      response.

PMID- 9629567
TI  - Phenotypic characterization of neuroleptic-sensitive neurons in the forebrain:
      contrasting targets of haloperidol and clozapine.
AB  - The prototypical neuroleptic haloperidol and the atypical antipsychotic clozapine
      induce distinctly different patterns of c-fos expression in the forebrain. While
      haloperidol appears to increase c-fos expression via its D2 dopamine receptor
      antagonist properties, the receptor mechanisms by which clozapine produces its
      unique pattern of c-fos expression are not known. The present experiments sought
      to address this question by determining the phenotypes of neurons in which
      clozapine increases Fos-like immunoreactivity (FLI). Fos immunostaining combined
      with in situ hybridization histochemistry using a cDNA oligonucleotide probe for
      D3 receptor mRNA indicated that the great majority (95%) of clozapine-induced FLI
      neurons in the major island of Calleja (ICjM) express D3 receptors. Similarly, in
      the nucleus accumbens (NAc) and lateral septal nucleus (LSN), the majority of
      clozapine-induced FLI neurons express D3 receptor mRNA (NAc 69%; LS 73%). In
      marked contrast, haloperidol-induced FLI neurons failed to express D3 receptors
      in any brain region. Studies with oligonucleotide probes for enkephalin (ENK) and
      dynorphin (DYN) indicated that clozapine increases c-fos expression in both ENK
      and DYN containing neurons in the NAc (ENK 40%, DYN 53%) and LSN (ENK 32%, DYN
      59%). Haloperidol also increases c-fos expression in ENK and DYN containing
      neurons, albeit in a different pattern (striatum: ENK 93%, DYN 20%; nucleus
      accumbens: ENK 46%, DYN 36%; lateral septum: ENK 29%, DYN 18%). The present
      results demonstrate that haloperidol and clozapine target different populations
      of neurons even in regions such as the NAc and LSN, where they both increase c
      fos expression. In addition, the fact that the majority of clozapine-sensitive
      neurons in NAc, LSN, and ICjM express D3 receptors suggests that activity at
      these receptors may contribute to the unique clinical profile of this
      antipsychotic agent. These data indicate that D3 receptors may represent novel
      targets in the pharmacotherapy of schizophrenia.

PMID- 9629568
TI  - Sustained withdrawal allows normalization of in vivo [11C]N-methylspiperone
      dopamine D2 receptor binding after chronic binge cocaine: a positron emission
      tomography study in rats.
AB  - In our previous positron emission tomography studies striatal binding for both
      [11C]SCH23390 and [11C]N-methylspiperone (NMSP) were decreased in the rat brain
      on the last day of chronic (14 days) binge cocaine administration. We have found
      that [11C]SCH23390 binding to dopamine D1 receptors returns to saline control
      levels within ten days withdrawal from chronic binge cocaine and remains at
      control levels after 21 days withdrawal. An 18% decrease in [11C]NMSP binding to
      dopamine D2 receptors was observed after ten days withdrawal. However,
      importantly, after 21 days withdrawal [11C]NMSP binding was at saline control
      levels. Changes of in vivo [11C]NMSP binding required a longer abstinence period
      for normalization than [11C]SCH23390 binding. The apparent recovery of dopamine
      D2 receptors after prolonged abstinence from chronic cocaine and the different
      rates of normalization for dopamine D1 versus D2 receptors may be critical
      information for development of pharmacotherapies for cocaine dependent patients.

PMID- 9629569
TI  - Presence and characterization of the serotonin transporter in human resting
      lymphocytes.
AB  - Although evidence exists of the presence of a serotonin (5-HT) reuptake system in
      lymphocytes, no information is available on the pharmacological characterization
      of this structure. Our study aimed to investigate this matter, therefore, by
      means of the binding of [3H]-paroxetine ([3H]PAR), a selective 5-HT reuptake
      inhibitor (SSRI), which is considered the ligand of choice for binding studies.
      Lymphocytes were obtained from a pool of 20 healthy subjects who volunteered for
      the study. The results showed the presence of a specific and saturable [3H]PAR
      binding to lymphocyte membranes, with a Hill number close to unity indicative of
      the presence of one site only. The most potent drugs inhibiting [3H]PAR binding
      were SSRIs (paroxetine, fluoxetine, citalopram) followed by clomipramine,
      imipramine, and 5-HT, whereas haloperidol, mazindol, and nomifensine had a
      negligible effect. These findings suggest that [3H]-PAR in human resting
      lymphocytes specifically labels the 5-HT transporter.

PMID- 9629571
TI  - Diagnostic imaging modalities during pregnancy.
AB  - This article discusses how imaging of distant disease, and imaging in general,
      may affect the fetus. Imaging examples of primary disease will be presented of
      the most common malignancies for women of child bearing years who happen to be
      pregnant.

PMID- 9629570
TI  - Ethical challenges in treating mother and fetus when cancer complicates
      pregnancy.
AB  - This article evaluates the complicated scenario for physicians when they must
      advise pregnant oncology patients and their families. Included in this discussion
      are a review of literature that addresses both maternal and fetal rights and an
      analysis of metaphysical considerations unique to this situation. Additionally,
      there is a presentation of philosophical ideations, including an introduction to
      the ethical principles of autonomy, beneficence, and authenticity, which are
      offered in an attempt to increase the physician's comfort level with this very
      difficult task.

PMID- 9629572
TI  - Radiation therapy during pregnancy.
AB  - Malignant disease requiring radiation therapy during pregnancy presents an
      enormous challenge for the clinician. The optimal radiotherapeutic management of
      the patient and the optimal management of the pregnancy involve directly opposing
      demands. Ionizing radiation should be avoided during pregnancy whenever possible.
      Doses in excess of 0.1 Gy (10 rad) delivered during gestation have been
      associated with various detrimental effects, and therapeutic abortion has been
      recommended. If radiation is unavoidable, such as in the treatment of some
      gynecologic tumors, lymphomatous diseases, or other advanced solid tumors, it
      must be performed with extreme caution and maximal effort to reduce the dose to
      the fetus by special shielding techniques. Decisions regarding the use of
      radiation therapy during pregnancy, the delay of therapy, or pregnancy
      termination should be made by a multidisciplinary team and be guided by the
      prognosis of the disease, the stage of gestation, the risk to the fetus from the
      expected fetal radiation dose, and the patient's ethical and religious beliefs.

PMID- 9629573
TI  - Chemotherapy in pregnancy.
AB  - There is limited information concerning the effects of chemotherapy administered
      during pregnancy, which consists mostly of case reports and small series. The
      National Cancer Institute maintains a registry of neonates exposed to
      chemotherapy but there are currently only several hundred cases. When
      chemotherapy is used during embryogenesis, there is an increased rate of
      spontaneous abortions and major birth defects. The risk of fetal malformations
      when chemotherapy is administered during the second and third trimesters is
      probably not greater than the background rate. Use in the second and third
      trimesters may increase the risk of premature birth, fetal growth restriction,
      maternal and fetal myelosuppression, and still births.

PMID- 9629574
TI  - Noninvasive cervical cancer complicating pregnancy.
AB  - The management of abnormal cytology during pregnancy has changed dramatically
      during the last 3 decades. The goal has been and remains timely diagnosis of and
      treatment planning for invasive carcinoma of the cervix. Because therapy for
      preinvasive disease can safely be postponed until the postpartum period, the
      ability to distinguish CIN from invasive cancer without cone biopsy has been a
      major step forward in the management of cervical disease in pregnancy. The data
      presented herein demonstrate the safety and accuracy of the more conservative
      approach of colposcopy and biopsy. The use of cone biopsy during pregnancy,
      associated with substantial morbidity, has been significantly reduced by the
      diligent application of colposcopy. As is true in the nonpregnant state, cone
      biopsy is necessary when colposcopic examination is nonsatisfactory. Cone
      biopsies cannot be considered therapeutic during pregnancy owing to the high
      incidence of positive margins and residual disease on postpartum evaluation. For
      this reason, the importance of postpartum reevaluation cannot be overemphasized.

PMID- 9629576
TI  - Breast disease complicating pregnancy.
AB  - Cancer complicating pregnancy is uncommon, with an incidence of approximately 1
      in 1000 pregnancies. The obstetrician attending 250 deliveries per year would
      need to accumulate 40 years of clinical experience to encounter two to three
      cases of PABC. The increases in the size, weight, vascularity, and density of the
      breasts associated with pregnancy make the detection of mass lesions difficult
      both clinically and mammographically. Most of the benign lesions seen in
      pregnancy are the same ones seen in the nongravid state. Most cases of PABC
      present as painless masses, and as many as 90% of these masses are detected by
      breast self-examination. Women with PABC generally have more advanced disease
      with larger tumors, a higher percentage of inoperable lesions, and a higher
      percentage of nodal involvement. Because most PABC presents with a palpable mass,
      the role of imaging modalities in the evaluation of these patients remains
      limited. Fine-needle aspiration cytology is the initial procedure of choice for
      evaluating breast masses during pregnancy and lactation. Therapeutic abortion
      does not improve survival. The general principle is to treat the cancer and to
      allow the pregnancy to proceed. No studies have shown an adverse effect of a
      subsequent pregnancy even in patients with positive axillary nodes and patients
      in whom pregnancy occurs earlier than 2 years after treatment.

PMID- 9629575
TI  - Invasive cervical cancer complicating pregnancy. How to manage the dilemma.
AB  - Pregnancy presents an ideal time for cervical cancer screening, and all pregnant
      women presenting for prenatal care should be carefully examined. Most patients
      with pregnancy-associated cervical cancer present with early-stage disease. The
      prognosis for pregnant patients after stratification for stage is similar to that
      for nonpregnant patients. A management algorithm is presented in Figure 2.
      Patients with early-stage squamous cancers diagnosed in the late second and early
      third trimester may have cancer treatment delayed to increase the likelihood of
      fetal maturity without compromising maternal prognosis. Cesarean section in
      patients with pregnancy-associated cervical cancer should be the delivery method
      of choice. Early-stage cervical cancer should initially be treated surgically. In
      patients with advanced disease, primary radiation therapy is a safe and effective
      modality. In the first and second trimester, radiation therapy should be
      performed without hysterotomy.

PMID- 9629577
TI  - Lymphoma and leukemia complicating pregnancy.
AB  - The hematologic malignancies rarely complicate pregnancy. Pregnancy is not
      thought to affect the course of either Hodgkin's lymphoma, non-Hodgkin's
      lymphoma, or the leukemias. The prognosis worsens only if there is a delay in
      diagnosis or treatment. Both chemotherapy and radiotherapy have been administered
      during pregnancy with favorable results.

PMID- 9629579
TI  - Thyroid cancer complicating pregnancy.
AB  - Thyroid nodules and thyroid cancer are more common in women than in men. It is
      not uncommon to find a thyroid nodule during pregnancy that requires
      investigation. Fortunately, most cancers found during pregnancy are
      differentiated thyroid cancers with an excellent prognosis. Fine-needle
      aspiration is safe and accurate during pregnancy. Cancer discovered early in
      pregnancy can safely be operated on in the second trimester. Cancers or nodules
      discovered later in pregnancy can have work-up and treatment delayed until after
      delivery. No data support pregnancy termination or the proscription of future
      pregnancy in these patients.

PMID- 9629578
TI  - Ovarian cancer complicating pregnancy.
AB  - Ovarian cancer is the second most frequent gynecologic cancer complicating
      pregnancy. Although uncommon, this is a topic that encompasses multiple aspects
      of obstetrics and gynecology. The management of the adxenal mass in pregnancy,
      surgery for ovarian cancer, chemotherapy during gestation, and the use of tumor
      markers during pregnancy are discussed.

PMID- 9629580
TI  - Melanoma complicating pregnancy.
AB  - The incidence of malignant melanoma is rising, and this may be the most
      frequently encountered malignancy during pregnancy. Because effective treatment
      of advanced or metastatic disease remains elusive, the key to adequate therapy is
      surveillance for early disease with prompt diagnostic work-up and treatment.
      Review of the most prominent reports in the literature fails to yield a consensus
      on whether pregnancy contributes to a worse prognosis. It seems clear that after
      controlling for all known prognostic variables, prognosis is unchanged; however,
      groups of patients diagnosed during pregnancy may have a disproportionately high
      incidence of high-risk primary lesion sites and increased tumor thickness.
      Surgical treatment during pregnancy should be prompt, with appropriate avoidance
      of general anesthesia during the first trimester. There is as yet insufficient
      evidence to warrant the use of adjuvant chemotherapy or biologic therapy during
      pregnancy.

PMID- 9629581
TI  - Colorectal cancer complicating pregnancy.
AB  - Colorectal carcinoma complicating pregnancy is rare but associated with a high
      maternal mortality rate. Stage for stage the survival data are the same for
      pregnant patients and nonpregnant controls, however diagnosis is often delayed
      due to pregnancy-associated gastrointestinal symptoms masking cancer symptoms. A
      high degree of suspicion, especially in high-risk patients, is the key to early
      detection and improved prognosis. Digital rectal exams, occult fecal blood tests,
      and flexible sigmoidoscopy or colonoscopy are performed as indicated. Treatment
      primarily consists of en-bloc resection of the malignancy and regional lymph
      nodes; timing of colorectal surgery and delivery are based upon clinical
      presentation, fetal age, and maternal desires.

PMID- 9629582
TI  - Reproductive sequelae of cancer treatment.
AB  - Remarkable advances have been made in the treatment of cancers that afflict
      patients of the reproductive age. Many survivors must now face the effects on
      gonadal function and have concerns about reproductive capacity. The sequelae of
      different modalities of cancer therapy specifically addressing surgery,
      chemotherapy, and radiotherapy on reproductive system are reviewed. Assisted
      reproductive technologies, prenatal diagnosis methods, and contraception
      counseling are briefly summarized in conclusion.

PMID- 9629583
TI  - Pregnancy-related impairments and the Americans with Disabilities Act.
AB  - Congress passed the Americans with Disabilities Act (ADA) in 1990. The ADA's
      overriding purpose is to provide a national mandate for the elimination of
      discrimination against individuals with disabilities. This article addresses the
      emerging relationship between pregnancy-related disabilities and the employment
      provisions of the ADA, set forth in title I of the Act. In view of the high
      percentage of women who will become pregnant and their potential need for
      workplace accommodations during and after pregnancy, it is crucial that health
      professionals understand the impact of the ADA's employment provisions.

PMID- 9629584
TI  - Detection of African horsesickness virus and discrimination between two equine
      orbivirus serogroups by reverse transcription polymerase chain reaction.
AB  - A reverse transcription polymerase chain reaction (RT-PCR), based on the gene
      encoding the NS2 protein of African horsesickness virus (AHSV), was developed for
      rapid serogroup-specific detection of AHSV. The specificity of RT-PCR products
      was confirmed by Southern blot hybridization using a radioactively labelled cDNA
      probe specific for the NS2 gene. This RT-PCR could discriminate between all known
      members of the AHSV and equine encephalosis virus serogroups. AHSV RNA was
      detected in a sample representing 0.005 plaque forming units in a dilution series
      made of infected cell culture material. In an immune horse which had been
      vaccinated with a baculovirus expressed AHSV (serotype 4) VP2 subunit vaccine,
      viral RNA could be detected for up to 22 weeks post challenge. AHSV RNA was
      detected in various organs of an infected horse. Viral RNA was also detected by
      RT-PCR in nine suspected field cases of African horsesickness while virus
      isolation was successfully performed on eight of these cases.

PMID- 9629585
TI  - Morphological confirmation of the separate species status of Culicoides
      (Avaritia) nudipalpis Delfinado, 1961 and C. (A.) imicola Kieffer, 1913 (Diptera:
      Ceratopogonidae).
AB  - Ten character states were used to compare five females and two males of two
      populations of C. nudipalpis from the Philippines and Timor in south-east Asia
      with 121 females and 167 males of 11 populations of C. imicola collected
      throughout its Afro-Asiatic range. It is concluded that they are closely related
      but good species, and together form a subgroup, or species-pair, in the imicola
      group; currently this Old World group of the subgenus Avaritia comprises seven
      described species. Culicoides nudipalpis and C. imicola are most reliably
      separated on the ratio of the length of the proboscis to the height of the head
      (P/H ratio: 0.66-0.73 in nudipalpis, 0.82-1.02 in imicola). Compared to C.
      imicola very little is known of the life habits of C. nudipalpis. The latter's
      close taxonomic relationship to C. imicola, a proven vector of African horse
      sickness (AHS) and bluetongue (BT), indicates that the capacity of C. nudipalpis
      to vector these orbiviruses deserves to be investigated.

PMID- 9629587
TI  - Suspected cardiac glycoside intoxication in sheep and goats in Namibia due to
      Ornithogalum nanodes (Leighton).
AB  - The main clinical and necropsy features of field and experimental cases of
      suspected cardiac glycoside intoxication following ingestion and dosing of the
      plant Ornithogalum nanodes, are described. The distribution of intoxication in
      the area as well as a description of the plant are given. Plant samples tested
      for cardiac glycosides by fluorescence polarization immuno-assay (FPIA) gave a
      strong positive reaction. This is a new finding, as other toxic Ornithogalum
      species in southern Africa are devoid of cardiac glycoside activity and poisoning
      with them result only in a severe, often fatal diarrhoea, without obvious cardiac
      involvement. It is also the first record of toxicity of this particular plant.

PMID- 9629586
TI  - Krimpsiekte in a sheep following a single dose of Tylecodon ventricosus (Burm.
      f.) Toelken and the isolation of tyledoside D from this plant species.
AB  - Tylecodon ventricosus induced severe respiratory distress in two penned sheep
      without any electrocardiographic abnormalities being recorded. Based on the
      results it appears as if T. ventricosus predominantly induces the neuromuscular
      syndrome referred to as krimpsiekte. A single, relatively large intraruminal dose
      of 10.0 g/kg induced krimpsiekte in one sheep. Treatment with 5.0 g/kg activated
      charcoal on two consecutive days did not prevent the development of krimpsiekte.
      A bufadienolide, tyledoside D, was isolated from semi-dried plant material.

PMID- 9629588
TI  - Distribution of endocrine cells in the gut of the impala (Aepyceros melampus).
AB  - Immunocytochemical methods were employed to demonstrate endocrine cells,
      containing peptides and serotonin, in the gut of the impala. Cells immunoreactive
      to serotonin, somatostatin, gastrin, cholecystokinin, glucagon, neurotensin,
      secretin, glucose-dependent insulinotropic peptide and motilin were detected.
      Antisera raised to substance P and pancreatic polypeptide failed to stain any
      cells. The distribution of these peptide-containing cells is more in line with
      the situation in sheep than other ruminants. In contrast, the distribution and
      abundance of serotonin cells in the gut of the impala parallels the situation
      seen in game herbivores.

PMID- 9629589
TI  - Detection and characterization of foot-and-mouth disease virus in sub-Saharan
      Africa.
AB  - Genomic amplification of the VP1 gene of SAT-type foot-and-mouth disease virus
      (FMDV) was performed with published and novel oligonucleotide primers. The primer
      pair with the highest SAT-type recognition (67%) was identified and selected for
      optimization. Modifications to primers significantly improved SAT-type detection
      (100%), broadened the recognition range to European (A, O and C) and Asian (Asia
      1) serotypes and improved test sensitivity. In addition to being able to confirm
      the presence of FMDV in a clinical specimen within 6 h of receipt, the PCR
      product, which is amenable to nucleotide sequencing, enables genetic
      characterization of viruses into serotype and topotype within 48 h. VP1 gene
      sequence analysis of isolates from seven African countries and representative of
      five of the six serotypes occurring on the continent, revealed that SAT-types
      have the highest levels of intratypic variation. Intratypic variation for the SAT
      types ranged from 34-40.4% on nucleotide level, and from 24.1-27.5% on amino acid
      level. In addition, the methodology presented here was shown to be useful for
      determining the origin and tracing the course of epizootics in both wild and
      domestic cloven-hoofed animals.

PMID- 9629590
TI  - Dynamics of free-living ixodid ticks on a game ranch in the Central Province,
      Zambia.
AB  - Free-living ixodid ticks were collected at monthly intervals from January to
      December 1996 by dragsampling the vegetation of Mtendere Game Ranch in the
      Chisamba District of the Central Province, Zambia. Ticks belonging to 11 species
      were recovered. Rhipicephalus appendiculatus was most abundant, comprising 90% of
      the total number collected. All life stages of this tick showed a definite
      seasonal pattern of activity. The adults were present mainly during the rainy
      season (February and March), the larvae during the cool and dry season (May to
      August), and the nymphs during the hot and dry season (August to October). Adults
      were most abundant in the wooded areas and nymphs in the open grasslands. Larvae
      of Amblyomma variegatum were only found from May to September, while larvae of
      Boophilus decoloratus were present throughout the year with peaks of abundance
      from January to February and again from August to November. Rhipicephalus evertsi
      larvae occurred throughout the year. Recent burning of the vegetation did not
      seem to affect the number of ticks collected. A possible burning regime to
      achieve a degree of tick control is discussed.

PMID- 9629591
TI  - Follow-up to the study: A randomized, double-blind, placebo-controlled consumer
      rechallenge test of Olean salted snacks.

PMID- 9629592
TI  - Human variability and noncancer risk assessment--an analysis of the default
      uncertainty factor.
AB  - A 10-fold uncertainty factor is used for noncancer risk assessments to allow for
      possible interindividual differences between humans in the fate of the chemical
      in the body (kinetics) and target organ sensitivity (dynamics). Analysis of a
      database on the variability in each of these aspects is consistent with an even
      subdivision of the 10-fold factor into 10(0.5) (3.16) for kinetics and 10(0.5)
      (3.16) for dynamics. Analysis of the number of subjects in a normally and log
      normally distributed population which would not be covered by factors of 3.16
      supports this subdivision and also the use of a 10-fold factor to allow for both
      aspects. Analysis of kinetic data for subgroups of the population indicates that
      the standard default value of 3.16 for kinetics will not be adequate for all
      routes of elimination and all groups of the population. A scheme is proposed
      which would allow the selection of appropriate default uncertainty factors based
      on knowledge of the biological fate and effects of the chemical under review.

PMID- 9629593
TI  - Toxicological risk assessment in the courtroom: are available methodologies
      suitable for evaluating toxic tort and product liability claims?
AB  - Courts are increasingly faced with the need to resolve claims by individuals that
      they have been injured by chemical exposures or that they have been put at
      sufficient risk by such exposures that their health status must be monitored to
      ensure the earliest possible detection of developing injuries or diseases. This
      paper offers the view that the principles and methods developed and applied by
      toxicologists, epidemiologists, and risk assessors to support regulatory and
      public health decision-making are inadequate to evaluate the types of claims that
      courts are called upon to resolve in such cases. No well-described alternative
      methodology appears to be available, and as a result, courts are exposed to a
      wide range of expert opinions based on diverse, conflicting, and sometimes
      baseless methodologies. It is suggested that there may be value in an effort by
      the community of professionals in toxicology, epidemiology, and risk assessment
      to devote attention to the types of data and scientific methodologies that might
      be appropriate for evaluating the technical questions that such claims provoke.
      Such an effort might assist trial judges in the role they have been assigned in
      the Supreme Court's 1993 Daubert decision, wherein they are asked to make a
      preliminary assessment of the admissibility of the scientific methodologies
      relied upon by various experts. Such an assessment, if based on an understanding
      of the types of data and methodologies suitable for evaluating claims of injury,
      offers the possibility of limiting the range of expert opinion that ultimately is
      heard in courtrooms to that which conforms to scientifically valid standards.

PMID- 9629594
TI  - Validating new toxicology tests for regulatory acceptance.
AB  - Before a new or revised toxicology test is considered acceptable for safety
      evaluation of new substances, the test users and the industrial and regulatory
      decision makers must feel comfortable with it, and the decisions it supports.
      Comfort with, and the acceptance of, a new test comes after knowing that it has
      been validated for its proposed use. The validation process is designed to
      determine the operational characteristics of a test, that is, its reliability and
      relevance, in addition to its strengths and limitations. The reliability of a
      test is measured by its reproducibility. Its relevance is judged by its
      mechanistic relationship to the health effects of concern, and its ability to
      predict or identify those effects. The U.S. government has recently formed the
      Interagency Coordinating Committee on the Validation of Alternative Methods
      (ICCVAM) to work with federal agencies and test developers to coordinate the
      evaluation and adoption of new test methods. The ICCVAM will provide guidance to
      agencies and other stakeholders on criteria and processes for development,
      validation, and acceptance of tests; coordinate technical reviews of proposed new
      tests of interagency interest; facilitate information sharing among agencies; and
      serve as an interagency resource and communications link with parties outside of
      the federal government on matters of test method validation.

PMID- 9629595
TI  - Use of EC criteria for determining health and environmental hazards for
      classification of chemicals for environmental risk.

PMID- 9629596
TI  - Do peroxisome proliferating compounds pose a hepatocarcinogenic hazard to humans?
AB  - The purpose of the workshop "Do Peroxisome Proliferating Compounds Pose a
      Hepatocarcinogenic Hazard to Humans?" was to provide a review of the current
      state of the science on the relationship between peroxisome proliferation and
      hepatocarcinogenesis. There has been much debate regarding the mechanism by which
      peroxisome proliferators may induce liver tumors in rats and mice and whether
      these events occur in humans. A primary goal of the workshop was to determine
      where consensus might be reached regarding the interpretation of these data
      relative to the assessment of potential human risks. A core set of biochemical
      and cellular events has been identified in the rodent strains that are
      susceptible to the hepatocarcinogenic effects of peroxisome proliferators,
      including peroxisome proliferation, increases in fatty acyl-CoA oxidase levels,
      microsomal fatty acid oxidation, excess production of hydrogen peroxide,
      increases in rates of cell proliferation, and expression and activation of the
      alpha subtype of the peroxisome proliferator-activated receptor (PPAR-alpha).
      Such effects have not been identified clinically in liver biopsies from humans
      exposed to peroxisome proliferators or in in vitro studies with human
      hepatocytes, although PPAR-alpha is expressed at a very low level in human liver.
      Consensus was reached regarding the significant intermediary roles of cell
      proliferation and PPAR-alpha receptor expression and activation in tumor
      formation. Information considered necessary for characterizing a compound as a
      peroxisome proliferating hepatocarcinogen include hepatomegaly, enhanced cell
      proliferation, and an increase in hepatic acyl-CoA oxidase and/or palmitoyl-CoA
      oxidation levels. Given the lack of genotoxic potential of most peroxisome
      proliferating agents, and since humans appear likely to be refractive or
      insensitive to the tumorigenic response, risk assessments based on tumor data may
      not be appropriate. However, nontumor data on intermediate endpoints would
      provide appropriate toxicological endpoints to determine a point of departure
      such as the LED10 or NOAEL which would be the basis for a margin-of-exposure
      (MOE) risk assessment approach. Pertinent factors to be considered in the MOE
      evaluation would include the slope of the dose-response curve at the point of
      departure, the background exposure levels, and variability in the human response.

PMID- 9629597
TI  - The evaluation and hazard classification of toxicological information for
      Workplace Hazardous Materials Information System material safety data sheets.
AB  - Hazardous materials used occupationally in Canada are subject to the legislated
      requirements of the Workplace Hazardous Materials Information System (WHMIS).
      This paper describes the administrative framework of WHMIS and how toxicological
      data are evaluated to determine if a substance triggers WHMIS classification for
      the toxicological endpoints of acute toxicity, skin irritation, eye irritation,
      corrosion, dermal sensitization, respiratory sensitization, chronic toxicity,
      mutagenicity, teratogenicity/embryotoxicity, and carcinogenicity. Problems
      encountered with the information on material safety data sheets are also
      discussed for each of the toxicological endpoints.

PMID- 9629598
TI  - Granulomas in the livers of humans and Fischer rats associated with the ingestion
      of mineral hydrocarbons: a comparison.
AB  - Ninety-day feeding studies were conducted in Fischer 344 rats using a series of
      highly refined mineral hydrocarbons which included mineral oils and waxes
      representative of those used in consumer products and food applications. The
      series included materials which had been refined by oleum or hydrogenation. The
      materials tested were representative of the range of carbon chain lengths,
      molecular weights, and viscosities which are currently in use. Findings revealed
      the presence of granulomatous lesions in the liver and histiocytosis in the lymph
      nodes. Some mineral hydrocarbons did not induce any lesions; others induced
      relatively minor effects; and a low melting point wax induced the largest lesions
      in both liver and mesenteric lymph nodes, with inflammation and areas of focal
      necrosis in the livers. The majority of lesions reported were associated with the
      highest dose levels used. These studies are in contrast to studies in Sprague
      Dawley rats in which comparable doses did not induce similar lesions, indicating
      marked strain variability. Lipogranulomas associated with the ingestion of
      mineral oil have been reported in humans. The comparative morphology of the
      lesions seen in the Fischer rat study and those observed in the human are
      discussed and differences are highlighted. The lesions in the human are not
      believed to progress to lesions of clinical significance. The pathogenesis of the
      lesions induced in Fischer rats and in humans is discussed and it is concluded
      that the majority, if not all of the lesions, in the rats are of no significance
      for humans. The possibility that a small proportion of cases of granulomatous
      hepatitis in humans may represent an atypical response to mineral hydrocarbons
      may need further investigation.

PMID- 9629599
TI  - What's in a name: toxicokinetics, pharmacokinetics, or just kinetics?

PMID- 9629600
TI  - An atypical result: noncorrosivity to skin and eye at pH 0.7.

PMID- 9629601
TI  - [Detection of the viral load and its use as a virological marker in the follow-up
      of HIV-1-positive patients].
AB  - The evaluation of viral load as virological marker and its clinical and
      immunological correlation are presented. The first viral load studies were
      performed during 1996 at the National Reference Center for AIDS in Argentina in
      HIV-1 positive patients derived from different Hospitals in Buenos Aires. The
      study included 216 HIV-1 positive patients, 49 females and 167 males. Plasma was
      used for evaluating viral load and a second sample was obtained in 25 of the 216
      patients for their monitoring. Viral load was performed using bDNA technique
      (Quantiplex HIV RNA assay 2.0, Chiron Corporation, USA). Other parameters such as
      CD4 count determined by flow cytometry and clinical stages according to CDC
      classification were obtained in order to correlate clinical and immunological
      status of the patients. When CD4 count was compared with viral load, the results
      showed a trend of viral RNA increase in plasma along with a decrease in CD4+
      lymphocytes. This trend was also observed to correlate with the progression to
      AIDS disease. In all groups of patients, considering either CD4 counts or
      clinical status, ranges of viral load values were broad. Thus, as shown by
      percentiles 25 and 75, patients with CD4 counts < 200/ml, presented viral load
      values between 18,395 c/ml to 215,425 c/ml and patients with > 200/ml viral RNA
      showed values from < 10,000 to 35,180 c/ml. Patients with CDC's A and B stages
      presented values from < 10,000 to 45,160 c/ml and 87,000 c/ml respectively, while
      patients classified as C had 10,582 to 215,000 c/ml. Results of two consecutive
      samples in the 25 patients showed the usefulness of this technique for monitoring
      antiretroviral therapy. Nevertheless, despite the tendency of viral load to
      increase along with the progression of the disease, the broad range of values
      suggested the importance of using both virological and immunological parameters
      for the management of HIV infected patients.

PMID- 9629602
TI  - [Presence of fecal coliforms, Escherichia coli and DNAse- and coagulase-positive
      Staphylococcus aureus, in "colonial" cheese sold in the city of Blumenau, Estado
      de Santa Catarina, Brazil].
AB  - Twenty cheese samples were collected at Blumenau (SC) and were submitted to
      analysis in order to verify the presence of fecal coliforms, Escherichia coli and
      Staphylococcus aureus. Among the 20 samples of cheese, analysis revealed that 70%
      and 20% respectively, were not within present legal specifications (Norma 001/87
      DNVSA) for fecal coliforms and Escherichia coli. For Staphylococcus, 95% of the
      samples were not within present legal specifications.

PMID- 9629605
TI  - [Bacteriological quality of Bendetti Lake (Santo Tome, Santa Fe Province,
      Argentina) and associated environmental variables].
AB  - The main objective was to determine the bacteriological quality of a shallow lake
      in the lower Salado River Basin (Bedetti, 31 degrees 40' S and 60 degrees 45' W).
      Seventy samples were tested by the most probable number (MPN) method, throughout
      three years. The number of thermotolerant coliforms was very variable: from 20
      MPN/100 ml to 130,000 MPN/100 ml. These variations were mainly associated to the
      local rains (rs = 0.4853, p = 0.0001) and to the hydrometric level-h-(rs =
      0.3835, p = 0.008). Statistically significant correlations between coliform
      bacteria and other variables (temperature, oxygen, pH, conductivity and
      transparency) were not found. The increase of coliforms associated to the
      increase of the hydrometric level indicates the presence of diffuse contamination
      sources. It was found that the rains affected the bacteriological quality,
      specially during the low water periods (h < 3.60). During the high water periods
      (h > 4.70) one of the main coliform contributor was represented by the incoming
      floating islans and aquatic macrophyte, from allochthonous fluvial systems. The
      coliform concentrations between the Bedetti lake and the Salado river were
      compared. The results show a better bacteriological quality of the lake
      (geometric average = 1,990/100 ml vs. 420/100 ml, n = 56) so that, connecting
      them by the construction of an artificial channel is not advisable.

PMID- 9629604
TI  - Influence of different cultural conditions on cellulase production by Nectria
      catalinensis.
AB  - The production of the extracellular cellulolytic enzyme system (endoglucanase,
      exoglucanase and cellobiase) of N. catalinensis was tested with different
      nitrogen sources, inorganic and organic ones, in liquid culture medium with
      microcrystalline cellulose. The nitrogen compounds used were: potassium nitrate,
      sodium nitrate, ammonium nitrate, ammonium phosphate, ammonium sulphate, ammonium
      chloride, ammonium carbonate, ammonium acetate, ammonium tartrate, urea, casamino
      acids, glycine, L-alanine, L-leucine, L-proline, L-lysine, L-aspartic acid, L
      glutamic acid, L-asparagine, L-glutamine, L-phenylalanine, L-tyrosine, L
      tryptophan, L-methionine and L-cysteine. Among these, ammonium nitrate and
      ammonium tartrate gave the highest yields of cellulases in 20-day-old cultures at
      a concentration equivalent to 0.75 g N/l in both cases. Optimal temperature for
      cellulase production, growth and cellulose degradation was 23 degrees C. On the
      other hand, an initial pH of 6.5 gave the highest yields of endoglucanase and
      cellobiase. In the same way, at pH 6.5, maximal growth and cellulose degradation
      were achieved. However, maximal exoglucanase production and glycogen content were
      reached at pH 7.5.

PMID- 9629603
TI  - [Accumulation of actin and adhesion to HEp-2 cells of strains of Escherichia coli
      isolated from children with diarrhea in Mendoza, Argentina].
AB  - E. coli strains are the major bacterial cause of diarrhea among children under 2
      years of age residing in Mendoza, Argentina. Detection of diarrheogenic E. coli
      is made after coproculture, by agglutination tests using O-group antisera
      including most enteropathogenic E. coli (EPEC) serogroups and others often
      isolated in diarrhea. Although there are many O serogroups and H serotypes of E.
      coli strongly associated with infantile diarrhea, a number of studies have shown
      differences in the rate of isolation of EPEC between cases and controls using DNA
      probes. We compared the diagnosis of EPEC infections by traditional serogrouping
      tests with other detection methods using cell culture, involving the screening of
      isolates for adherence patterns to HEp-2 cells. A total of 140 isolates from
      children less than 24 months old with acute, persistent and chronic diarrhea and
      40 isolates from controls were recovered. Three distinct patterns of adherence,
      termed localised (LA), diffuse (DA) and aggregative (EAgg) adherence were found.
      The fluorescence actin staining assay was used as indicative of the ability of
      some EPEC strains that produce attaching-effacing (A/E) lesions. Positive
      serogrouping strains were strongly associated with adherence (P = 0.0001). LA
      adherence pattern occurred in 11% of cases with acute diarrhea associated with
      these serogroups (P = 0.001) and children under 12 months (P = 0.0001). The FAS
      test was positive in 80% of them. EAgg adherence was found only in patients (20%
      P = 0.0001) and DA occurred both in cases (29%) and controls (2.5% P = 0.0001).
      Diagnosis of EPEC infections has traditionally been performed by identifying
      organisms belonging to a number of serogroups or serotypes epidemiologically
      linked to diarrhea. Evidence is presented in this paper to show that
      pathogenicity is not restricted to serogroups. Isolation of many adherent strains
      not belonging to traditional EPEC O serogroups, shows the need for alternative
      methods to be used to detect and identify E. coli.

PMID- 9629606
TI  - [Candida dubliniensis: 1st isolation in Argentina].
AB  - We report the first isolation of Candida dubliniensis in Argentina. This strain
      was isolated from an oral lesion of an adult patient with AIDS during one
      recurrent episode of a previously treated oropharingeal candidosis. Phenotypic
      and genotypic characteristics coincided with those described by Sullivan et al.,
      who was the first to study this new species.

PMID- 9629607
TI  - [Methods for preserving bacterial cultures].
AB  - A wide variety of techniques are available for the preservation of bacteria and
      it may be difficult to choose a method for a particular strain, which not only
      assures survival, but which also makes certain that the genotype and hence the
      unique characteristics do not change. This paper provides a summary of the main
      features of various available methods with references to recent research and
      applications.

PMID- 9629610
TI  - Shoe-surface interaction and the reduction of injury in rugby union.
AB  - While it is quite clear that footwear can provide protection against lower limb
      injury in running and some court sports, the literature related to footwear
      design and injury prevention in most sports played on natural turf is limited.
      Nowhere is this more apparent than in the design of footwear for rugby union and
      rugby league. Therefore, in this article, information from other sporting codes
      will be applied to the design and performance characteristics of footwear and
      surfaces in an attempt to understand the causes of equipment-related injuries in
      rugby. A complete understanding of the complex interactions between the leg,
      foot, footwear and the surface has not yet been achieved and as a consequence,
      precise footwear design criteria to minimise injury, while not compromising the
      performance aspects of shoe design, have yet to be established. The variable
      surface conditions experienced by players makes it difficult to provide
      recommendations as to the ideal footwear for all (or any) conditions. Equally,
      the ground reaction loads experienced by each player (and playing position) vary
      sufficiently to make generalisations difficult. Also the foot-fall pattern during
      weight-bearing is highly individualised and further prohibits making general
      recommendations about selecting footwear for rugby.

PMID- 9629608
TI  - Effectiveness of external ankle support. Bracing and taping in rugby union.
AB  - Ankle inversion sprain is common in rugby. This review outlines research evidence
      relating to the effects of external ankle support by means of bracing and taping,
      on the incidence of ankle injuries, how performance is affected by support, how
      support may act at the joint (with respect to end range of motion, strength,
      resistive torque, muscle activation patterns and proprioception) to prevent
      injury, and how exercise changes the effectiveness of support. In addition, the
      implications of the laws of rugby for the use of external support are discussed.
      Prospective epidemiological studies have shown a decrease in the incidence of
      ankle injury with external ankle support use. The effectiveness of external ankle
      support was dependent upon the material properties and application method of the
      tape or brace, and on the athlete's status of ankle stability or previous injury.
      Experimental studies have indicated that the degree of ankle inversion
      restriction provided, and the degree of loss of restriction after exercise, were
      dependent upon the external support tested. External ankle support has been
      reported to have no effect on performance, or to have an adverse effect on
      performance in a variety of movement tasks. No prophylactic external ankle
      support has been shown to improve performance. If an external support is to
      provide mechanical support to a ligament it should exceed the strength of the
      ligament, which for the anterior fibular ligament is a force limit of between 6
      and 56 kg. Tape can provide only limited mechanical support of the ankle joint
      complex, but it may have proprioceptive effects. Taping may work as a
      psychological reminder, so that the athlete consciously moderates lower limb
      loading behaviour. There is equivocal evidence of the effect of brace use on
      ground reaction force excursions, balance ability and ankle strength. It is
      concluded that while there have been many investigations of the effects of tape
      and some forms of brace on ankle range of motion with and without exercise, there
      is equivocal evidence regarding the mechanism by which an external support acts.
      It is recommended that future research address the effects of external ankle
      support during dynamic exercise and that brace manufacturers utilise the
      information in the development of future brace designs to help reduce the risk of
      ankle inversion sprain injury. As external support can decrease the incidence of
      ankle inversion sprain the International Rugby Board should consider the use of
      ankle braces in rugby, allowing for stiff lateral components of the brace.

PMID- 9629609
TI  - External knee support in rugby union. Effectiveness of bracing and taping.
AB  - Rugby football is associated with a number of biomechanical stresses which are
      frequently associated with knee injury. Consequently, there has been a
      significant interest within the game regarding the techniques of knee surgery and
      accelerated rehabilitation and the prophylactic use of external knee support.
      Knee bracing and strapping techniques are widely practised by rugby players but
      their results vary and there are mixed opinions over their usefulness. This
      article discusses the current trends in external knee support, draws on the
      experiences of other professional football codes and extrapolates these to the
      rugby union setting. Widespread opinion confirms that improper or incomplete
      rehabilitation is linked to re-injury. There is also a general acceptance that
      external support for the knee in sport should never be used to mask an injury.
      There is no evidence that the prophylactic taping of the knee joint provides any
      significant external stabilisation for more than the first few minutes of play.
      This lack of lasting stabilisation is due to the vigorous physical activity
      associated with rugby which results in a rapid loss of the custom fit of the
      external support to the profile of the joint. The taping the patella to reduce
      the pain associated with poor patellar alignment is considered to be effective;
      however, the correction of other biomechanical influences is also important.
      Adhesive tape, when applied correctly, will reposition the patella but this
      technique is limited by factors such as sweating and movement. A number of knee
      braces are currently available and these are classified according to their
      prophylactic, rehabilitative or functional design. In this article, their use in
      rugby applies to external support as an aid to rehabilitation rather than injury
      prevention.

PMID- 9629611
TI  - The use of padding in rugby union. An overview.
AB  - In any contact sport where impact and collision are an accepted feature, the use
      of various forms of external padding has become more common. Rugby union players
      experience a combination of characteristic extrinsic forces through the acts of
      tackling and scrummaging. The laws which are part of the international regulation
      of rugby union only permit the wearing of certain, clearly delineated forms of
      padding. Only then is such padding permitted on medical recommendation, provided
      that this padding is attached to the body or sewn into the jersey. This article
      discusses the padding of the shoulders, shins and thighs of rugby union players
      and highlights the need to address these issues with respect to the increasing
      number of women who are now playing this sport, particularly in the Southern
      hemisphere. There is little evidence to show that shoulder pads decrease the
      incidence of severe shoulder injuries. However, well-fitting shoulder pads
      constructed of materials that effectively disperse the force of impact appear to
      reduce the effect of direct contact and reduce the potential for soft tissue
      damage. Shin guards that are made of light, soft, compliant materials are
      effective in reducing impact to the shin and thereby reduce the risk of bruising
      injuries which are common to the pretibial region. Similarly, thigh pads are
      considered to be able to modify the effects of direct contact forces to the
      anterior thigh where deep contusional injuries with the potential for myositis
      ossificans are well reported. Informed advice for women rugby players regarding
      the use of specific padding is unavailable at present. Current information is
      anecdotal and not confirmed by statistical studies or well-conducted research. In
      these circumstances, women rugby players should observe the same recommendations
      that apply to their male counterparts.

PMID- 9629612
TI  - Protective headgear in rugby union.
AB  - This article interprets the studies performed on the use of headgear in sport
      which relate to rugby. The design and testing of helmets and their effective use
      for protection in sport in general appears to be well documented. This is not the
      case for the use of protective headgear in rugby. Nevertheless, some conclusions
      and recommendations are warranted. Protection from the range of impacts that can
      arise through participation in contact sports does not seem to be attainable by
      using protective helmets or protective rugby headgear. However, the use of
      headgear is recommended for protection against lacerations and abrasions and to
      provide a limited protection from injury caused by impact. Referees should
      discourage the use of protective headgear, to manipulate an opponent by using the
      rules to eliminate such behaviour. Coaches, athletes and administrators must be
      committed to the practice of safe performance skills, for example, by not using
      the head as an implement and not targeting the headgear of the opposing player.
      Further research is required to determine the effectiveness of protective
      headgear in reducing the risk of injury in rugby, whether the use of headgear
      places a player at a greater risk of injury through altered behaviour and the
      reasons why players currently choose not to wear headgear.

PMID- 9629615
TI  - Weight and survival depression in rodent bioassays with and without tumor
      decreases.
AB  - It has been suggested that the decreased tumor rates (anticarcinogenicity)
      commonly observed in the National Toxicology Program (NTP) rodent bioassays may
      be caused by compound-induced decreases in body weight or decreases in survival
      of treated animals. In this study, weight decrement and survival depression
      following chemical treatment was studied for those chemicals which induce site
      specific decreases in tumor rates (anticarcinogens) and those which do not (non
      anticarcinogens) in a database of 312 chemicals tested in the NTP bioassay
      program prior to 1983. There is an evident difference in weight depression and
      animal survival between anticarcinogens and non-anticarcinogens but it is small
      relative to the variability between chemicals in the two groups. We argue that
      weight or survival depression cannot, in a simple way, explain the difference
      between anticarcinogenic and non-anticarcinogenic chemicals. In fact, there are a
      number of chemicals that are anticarcinogenic with no evidence of weight or
      survival depression and many chemicals that cause significant weight or survival
      decreases with no apparent anticarcinogenic effects. There is a small but
      statistically insignificant relationship between the degree of weight depression
      and the number of tumor sites found to have lower tumor rates in treated animals.
      These analyses suggest that biological factors other than weight and survival
      depression are involved in decreased tumor rates in rodent bioassays. These
      results, and those of the companion paper (I. Linkov et al., this issue), suggest
      that the anticarcinogenic responses observed in rodent cancer bioassays should be
      carefully considered in evaluations of the overall carcinogenic potential of
      chemicals.

PMID- 9629613
TI  - Mouthguards. Protection for the mouth in rugby union.
AB  - The mouthguard is a resilient device or appliance which is placed inside the
      mouth to protect against injuries to the teeth, lacerations to the mouth and
      fractures and dislocations of the jaw. There is clear support in the scientific
      literature for the use of mouthguards in contact sports such as rugby. Moreover,
      there is evidence that mouthguards are effective in protecting against concussion
      and injuries to the cervical spine. There is a high level of acceptance of
      mouthguards by players and an increasing number are regularly wearing
      mouthguards. This is especially true among the elite players, but acceptance and
      wearing rates are moderately high among club players as well. There is strong
      support among players and researchers for mouthguard wearing to be made
      compulsory. It is generally recommended that: (i) mouthguards be worn during both
      practice sessions and games; (ii) the habit of wearing a mouthguard begins at an
      early age; (iii) mouthguards be regularly replaced while children are still
      growing; and (iv) adult players replace their mouthguards at least every 2 years.
      The selection of a mouthguard will depend on a number of factors including the
      age of the individual, effectiveness and cost. The type I (stock), or 'off-the
      shelf', mouthguards are considered inferior when compared with the other
      available types, and their use is discouraged. Type II (mouth-formed) mouthguards
      come in 2 forms, the shell-liner version and the popular thermoplastic 'boil and
      bite' version. While the effectiveness of the shell-liner mouthguard was examined
      in one experimental study, no such research has been reported for the
      thermoplastic mouthguard. Type III (custom-fabricated) mouthguards are
      recommended for players playing in the more vulnerable positions and in the
      higher grades. Most experimental studies in which the effectiveness of
      mouthguards has been demonstrated have involved type III mouthguards.

PMID- 9629614
TI  - Anticarcinogenic responses in rodent cancer bioassays are not explained by random
      effects.
AB  - Anticarcinogenicity in a long-term rodent bioassay is defined as a statistically
      significant decrease of a specific tumor type in a dosed group following chemical
      exposure. About 92% of chemicals tested by the National Toxicology Program prior
      to 1983 reveal at least one site with a significant (p < or = 0.05) tumor rate
      decrease in one or more tested groups, a result consistent with those of J. K.
      Haseman and F. M. Johnson (1996, Mutat. Res. 350, 131-141) for a database of
      recently tested chemicals. Detection of tumor decreases in a specific site can be
      explained not only by biological effects, but also as a result of random
      variability in the background tumor rates, decreases in body weight, or decreases
      in survival of treated animals. This paper evaluates the rate of false-positive
      anticarcinogenic findings due to random effects (variations in tumor rates and
      the multiple comparisons undertaken in evaluating a bioassay), while a companion
      paper addresses the influence of weight and survival depression. Monte-Carlo
      simulation was conducted to assess the contribution of random effects. This
      contribution was found to be important even when a statistical significance
      cutoff of p0 < or = 0.05 was chosen. If a more stringent statistical criterion
      was used (p0 < or = 0.01 or p < or = 0.005), the proportion of false positive
      determinations diminishes. The number of anticarcinogens in the database remains
      substantially higher than predicted by the stimulations. An examination of the
      distribution of all p values (T. Schweder and E. Spjotvoll, 1982, Biometrika 69,
      493-502) also indicates that statistically significant anticarcinogenic responses
      are found in the database at a higher rate than would result from purely random
      responses. Finally, the cross-species prediction of anticarcinogenic responses
      was examined in a manner similar to a study of cross-species prediction of
      carcinogenic responses (G. M. Gray et al., 1995, Reg. Toxicol. Pharmacol. 20, 281
      301). The analyses show that anticarcinogenic effects in one rodent species
      predict well anticarcinogenic effect in another rodent species. It seems likely
      that biological factors are involved in anticarcinogenic responses observed in
      rodent cancer bioassays.

PMID- 9629616
TI  - Acrylic acid induces the glutathione-independent mitochondrial permeability
      transition in vitro.
AB  - Acrylic acid (AA) is used widely in the synthesis of esters essential in the
      production of paints, adhesives, plastics, and coatings. The minimal systemic
      toxicity of AA is attributed to its rapid oxidation to acetyl-CoA and CO2 via the
      vitamin B12-independent beta-oxidation pathway. This oxidation is localized to
      the mitochondria and preliminary evidence suggests a possible inhibition of
      mitochondrial metabolism by acrylic acid. The purpose of this investigation was
      to evaluate whether AA interferes with mitochondrial bioenergetics in vitro.
      Incubation of isolated rat liver mitochondrial with AA resulted in a dose
      dependent induction of the mitochondrial permeability transition (MPT). This was
      evidenced by an increased sensitivity to calcium-induced stimulation of state 4
      oxygen consumption, depolarization of membrane potential, and swelling, all of
      which were prevented by preincubating the mitochondrial with cyclosporine A, a
      potent and specific inhibitor of the mitochondrial permeability transition pore.
      Both N-ethylmaleimide (NEM) and dithiothreitol (DTT) showed only partial
      protection against induction of the MPT by AA. Associated with the induction of
      the MPT by AA was the loss of mitochondrial glutathione (GSH), which was due to
      efflux from the matrix rather than oxidation to GSSG. Cyclosporine A, by
      inhibiting the permeability transition, prevented the AA-induced loss of
      mitochondrial GSH. In conclusion, AA increases the sensitivity of isolated
      mitochondria in vitro to the calcium-dependent induction of the MPT. Although the
      molecular mechanism has yet to be defined, it does not appear to be related to
      the oxidation of critical thiols.

PMID- 9629617
TI  - Toxicology and humoral immunity assessment of decamethylcyclopentasiloxane (D5)
      following a 1-month whole body inhalation exposure in Fischer 344 rats.
AB  - D5 is a low-molecular-weight cyclic siloxane used for industrial and consumer
      product applications. The objective of the present study was to assess potential
      toxic and immunomodulatory consequences of inhalation exposure to D5. Male and
      female Fischer 344 rats (25/group) were exposed by whole body inhalation to 0,
      10, 25, 75, or 160 ppm D5 6 h/day, 7 days/week for 28 days. Clinical signs, body
      weights, and food consumption were recorded. On the day following the final
      exposure, 10 rats/group/sex were euthanized and a complete necropsy performed.
      Following a 14-day nonexposure recovery period, the remaining 5 rats/sex/group
      were necropsied. Body and organ weights were obtained and a complete set of
      tissues was taken for histopathology. Samples were also collected for serum
      chemistry, hematology, and urinalysis. Immunotoxicology-designated rats
      (10/sex/group) were immunized with sheep erythrocytes (sRBC) 4 days prior to
      euthanasia and cyclophosphamide (CYP) was administered i.p. to positive controls
      on days 24 through 28. The anti-sRBC antibody-forming cell (AFC) response was
      evaluated in a standard plaque assay. Blood was also collected for examination in
      the anti-sRBC enzyme-linked immunosorbant assay (ELISA). D5 exposure did not
      modulate humoral immunity, while the internal control, CYP, produced the expected
      suppression of the AFC response. D5 exposure caused no adverse effects on body
      weight, food consumption, or urinalysis parameters. Serum alkaline phosphatase
      (SAP) was significantly decreased in females at terminal (12%, 160 ppm) and
      recovery sacrifice. A significant increase in the liver-to-body weight ratio was
      observed in female animals at the end of exposures (13%, 160 ppm), but was not
      noted in recovery animals from the same exposure group. In males, significant
      increases in liver-to-body weight (5%) and thymus-to-body weight (14%) ratios
      were also noted at the high dose at terminal sacrifice and were not present at
      recovery. At recovery only, a significant increase in spleen-to-body weight
      ratios (14 and 17%; 25 and 160 ppm, respectively) was noted. At the end of
      exposure, histopathological analysis indicated an increased incidence and
      severity of nasal (Level 1) goblet cell proliferation. Focal macrophage
      accumulation in the lung was also observed to be increased in incidence in both
      sexes at 160 ppm. At the end of the recovery period, the effects in both of these
      organs appeared to be reversible. In summary, D5 inhalation exposure did not
      alter humoral immunity and caused only minor, transient changes in hematological,
      serum chemistry, and organ weight values. Histopathological changes were confined
      to the respiratory tract and appeared to be reversible. The no observed effect
      level for systemic toxicity, based primarily on the liver weight changes, was 75
      ppm.

PMID- 9629618
TI  - Use of the mouse intranasal test (MINT) to determine the allergenic potency of
      detergent enzymes: comparison to the guinea pig intratracheal (GPIT) test.
AB  - A mouse intranasal test (MINT) was developed to determine the relative
      allergenicity of detergent enzymes. In this simple method, various doses of the
      enzymes are administered in a detergent matrix, via intranasal instillation, on
      days 1, 3, and 10, with serum samples collected on day 15. The sera are then
      analyzed for enzyme specific IgG1 antibody by an antigen specific enzyme
      immunoassay. The protease enzyme Alcalase (protease Subtilisin Carlsberg) has
      been used as a benchmark enzyme for development and characterization of the
      model. The objective of the current studies was to obtain potency comparisons
      with other protease and nonprotease enzymes and to begin to assess the validity
      of the model by comparison with potency determinations obtained with the guinea
      pig intratracheal (GPIT) test. The range of potencies detected among several
      enzymes of different classes was approximately 60-fold (compared with Alcalase).
      Modification of the dosing regimen to permit slightly more extended dosing did
      not change the relative potency determination. Comparison of data from the MINT
      and GPIT methods indicate that both the mouse and the guinea pig recognize the
      bacterial amylase Termamyl and a fungal exocellulase as more potent than
      Alcalase, a serine protease (Subtilisin B) and a fungal alpha-amylase (Fungamyl)
      as less potent than Alcalase, and the serine protease, Savinase, as equivalent to
      Alcalase. Also, these data are in alignment with clinical data on the prevalence
      of occupational enzyme sensitization. Given the simplicity and low cost of the
      MINT method compared with the GPIT test, these results support continued
      development of the method as an alternative approach for assessing the
      allergenicity of enzymes.

PMID- 9629620
TI  - Exposure-based safety evaluation of recombinant human macrophage colony
      stimulating factor (M-CSF) in cynomolgus monkeys.
AB  - The safety of M-CSF was assessed in cynomolgus monkeys in an intravenous dosing
      regimen. Exposure (AUC0-24) multiples (monkey vs human) were calculated using the
      no observable adverse effect level (NOAEL) observed in this study and correlated
      with known M-CSF-induced toxicities in a previous continuous intravenous infusion
      (civ) study in monkeys. M-CSF was administered by daily intravenous infusion (2
      h) to cynomolgus monkeys (2/sex/ group) at 0.1, 0.3, 0.7, and 1.0 mg/kg/day, for
      28 consecutive days. Control animals (2/sex) received placebo. The 0.7 mg/kg/day
      group was held for an additional 4-week recovery period. Criteria evaluated
      included physical observations, ophthalmoscopy, electrocardiography, body weight,
      food consumption, clinical pathology, antibody formation, pharmacokinetics,
      necropsy, organ weights, and histopathology. The only effect previously seen in
      monkeys after intravenously administered M-CSF occurred in animals in the 0.7 and
      1.0 mg/kg/day groups. They exhibited a slight decrease in platelets between days
      4 and 12 with subsequent recovery. No effects related to M-CSF administration
      were evident in macroscopic or microscopic evaluations and there was no evidence
      of anti-M-CSF antibody production. M-CSF at all dose levels was completely
      eliminated within each dosing interval with no accumulation. Clearance of M-CSF
      was enhanced during the first week of dosing, but returned to baseline clearance
      levels by day 27. This dosing regimen was shown to be remarkably free of
      toxicities noted in a previous monkey study where M-CSF was given by civ at
      similar daily doses. At the high dose, which was considered to be the NOAEL, the
      AUC0-24 was 40-fold greater than the AUC0-24 in clinical trials where 2.0 mg/m2
      was administered by a daily 2-h infusion.

PMID- 9629619
TI  - Male reproductive tract malformations in rats following gestational and
      lactational exposure to Di(n-butyl) phthalate: an antiandrogenic mechanism?
AB  - Di(n-butyl) phthalate (DBP), a widely used plasticizer suspected of having
      estrogenic properties, was investigated for its effects on the prenatal and early
      neonatal development of the reproductive tract. Pregnant CD rats (n = 10) were
      given DBP at 0, 250, 500, or 750 mg/kg/day (p.o.) throughout pregnancy and
      lactation until their offspring were at postnatal day 20. Maternal body weights
      throughout the dosing period were comparable in all groups. At 750 mg/kg/day, the
      number of live pups per litter at birth was decreased and maternal effects on
      pregnancy and postimplantation loss are likely to have occurred. Anogenital
      distance was decreased at birth in the male offspring at 500 and 750 mg/kg/day.
      The epididymis was absent or underdeveloped in 9, 50, and 71% of adult offspring
      (100 days old) at 250, 500, and 750 mg/kg/day, respectively, and was associated
      with testicular atrophy and widespread germ cell loss. Hypospadias occurred in 3,
      21, and 43% of males and ectopic or absent testes in 3, 6, and 29% of males at
      250, 500, and 750 mg/kg/day, respectively. Absence of prostate gland and seminal
      vesicles as well as small testes and seminal vesicles were noted at 500 and 750
      mg/kg/day. Vaginal opening and estrous cyclicity, both estrogen-dependent events,
      were not affected in the female offspring, although low incidences of
      reproductive tract malformations were observed at 500 and 750 mg/kg/day. In the
      male offspring, DBP produced the same spectrum of effects elicited by the
      antiandrogen flutamide. Thus, DBP specifically impaired the androgen-dependent
      development of the male reproductive tract, suggesting that DBP is not estrogenic
      but antiandrogenic in the rat at these high dose levels. For human risk
      assessment, determining if this toxicity is metabolite-mediated will be critical,
      since marked species differences in metabolism exist.

PMID- 9629621
TI  - Chronic ingestion of uranium in drinking water: a study of kidney bioeffects in
      humans.
AB  - A study was conducted of the chemical effects on the human kidney induced by the
      chronic ingestion of uranium in drinking water. Subjects were divided into two
      groups: The low-exposure group, whose drinking water was obtained from a
      municipal water system and contained < 1 microgram uranium/L, and the high
      exposure group, whose drinking water was obtained from private drilled wells and
      contained uranium levels that varied from 2 to 781 micrograms/L. Years of
      residence varied from 1 to 33 years in the low-exposure group and from 3 to 59
      years in the high-exposure group. The indicators of kidney function measured in
      this study included glucose, creatinine, protein, and beta 2-microglobulin (BMG).
      The markers for cell toxicity studied were alkaline phosphatase (ALP), gamma
      glutamyl transferase (GGT), lactate dehydrogenase (LDH), and N-acetyl-beta-D
      glucosaminidase (NAG). Urinary glucose was found to be significantly different
      and positively correlated with uranium intake for males, females, and pooled
      data. Increases in ALP and BMG were also observed to be correlated with uranium
      intake for pooled data. In contrast, the indicators for glomerular injury,
      creatinine and protein, were not significantly different between the two groups
      nor was their urinary excretion correlated to uranium intake. These results
      suggest that at the intakes observed in this study (0.004 microgram/kg to 9
      micrograms/kg body wt), the chronic ingestion of uranium in drinking water
      affects kidney function and that the proximal tubule, rather than the glomerulus,
      is the site for this interference.

PMID- 9629622
TI  - [100 years radiotherapy. On the birth of a new specialty].
AB  - Radiotherapy was founded as a new scientific specialty by the Viennese physician
      Leopold Freund 100 years ago. Freund provided the world's first scientific proof
      of the biological effectiveness of x-rays and performed the first successful
      treatment with these new rays on a 5-year old girl suffering from a huge nevus
      pigmentosus pilosus (hairy nevus) on her back. Before Freund's historical three
      experimental x-ray treatments (the first of these began on November 24, 1896, in
      Vienna) there had been earlier attempts and suggestions to apply x-rays
      therapeutically during 1896. However, none of these previous therapeutic attempts
      was successful. Also, there was no scientific proof of the biological
      effectiveness of x-rays among the therapeutic attempts which preceded Freund's
      fundamental x-ray treatments. Modern radiotherapy and radiation oncology
      contribute towards nearly one half of all cancer cures. Two thirds of cancer
      patients need the help of radiation oncology, and this scientific specialty is,
      thus, the most frequently used treatment modality in the management of tumor
      patients.

PMID- 9629623
TI  - [Malaria therapy in the era of chloroquine resistance].
AB  - Despite few efforts to develop new antimalarial compounds by the major
      pharmaceutical companies, some promising new therapeutics have been developed and
      tested clinically by small groups and companies throughout the world. Really new
      substances are scarce but combinations of known medicarnents have been shown to
      be a rational and effective approach to overcome problems with single compounds.
      Additionally, combination regimens are more easily authorized and accepted for
      treatment than completely new substances. Some examples in this respect are
      combinations of either atovaquone, doxycycline or clindamycin with a 'classical'
      antimalarial. Artemisinin, benflumetol and pyronaridine were originally developed
      in China and disperse currently to the rest of the world. First independent and
      international clinical trials gave promising results and one should bear in mind
      those substances for future applications. Especially artemisinin and its
      derivatives are of great interest because they represent, besides quinine, the
      only other therapeutic option for the treatment of multidrug-resistant severe
      malaria.

PMID- 9629624
TI  - Biochemical parameters of bone turnover in kidney transplant recipients.
AB  - Impairment of bone remodelling due to chronic renal failure persists even after
      successful kidney transplantation. Bone turnover was assessed in 22 kidney
      transplant recipients by measurement of serum bone markers: total (tALP) and bone
      alkaline phosphatase (bALP), osteocalcin (OC), procollagen I C-terminal
      propeptide (PICP), collagen I C-terminal telopeptide (ICTP), and iPTH. The
      patients were on dialysis 56.6 +/- 43.1 months before transplantation (mean +/-
      SD) and 34.2 +/- 23.0 months had elapsed after transplantation. The bone markers
      were within the reference range in 23% of patients for iPTH, 73% for tALP and 82%
      for bALP, 41% for OC, 73% for PICP and 50% for ICTP. A positive correlation was
      found between dialysis duration and ICTP, and iPTH and bone formation markers
      (OC, bALP). The obtained results indicate that bone turnover was increased after
      kidney transplantation, with prevailing bone resorption, which seems to be
      influenced by dialysis duration.

PMID- 9629625
TI  - Cardiac effects of sumatriptan: findings of Holter monitoring and review of the
      literature.
AB  - The aim of this study was to elucidate possible electrocardiographic effects of
      sumatriptan in a selected group of patients with severe headache requiring in
      patient treatment. The patients (n = 21) were treated with sumatriptan in
      addition to various other compounds and were asked to record any symptoms
      following the administration of sumatriptan. In addition, Holter monitoring was
      performed in all subjects. In agreement with other studies, the adverse events
      reported by the patients were not related to ECG changes and, vice versa, ECG
      changes were not accompanied by clinical symptoms. The Holter findings before and
      after administration of sumatriptan were significantly different in three
      patients, i.e. recurrent episodes of ST depression and increase in extrasystoles.
      These changes occurred within a period of 1.45 to 18 hours and were not
      reproducible when Holter monitoring was repeated without sumatriptan. Even though
      the findings might be explained by spontaneous variability of Holter monitoring
      or other factors, this study does not definitely discount the possibility that
      sumatriptan may cause ST segment changes and increase pre-existing extrasystoles.
      Controlled studies are required to clarify this issue.

PMID- 9629626
TI  - The clinical significance of antinuclear antibodies in connective tissue disease.
AB  - Antinuclear antibodies (ANA) are often present in connective tissue diseases. In
      279 non-selected patients with connective tissue disease, inflammatory and
      degenerative joint disease, in some patients with chronic infectious diseases and
      malignancies and in the presence of some unclear pathologic conditions in
      patients whose serum reacted positively to ANA, we analyzed the type of
      immunofluorescence and the presence of extractable antinuclear antibodies (ENA).
      In systemic lupus erythematosus, the prevailing immunofluorescence is type H
      (homogenous) (60.6%), anti-Ro/SS-A appears in 24.2%, anti-Sm and anti-RNP in
      12.1%. In Sjogren's syndrome, type S prevails (47.6%), anti- Ro/SS-A and anti
      La/SS-B are present in 52.4%, only anti-Ro/SS-A in 28.6%. In systemic sclerosis,
      the prevailing immunofluorescence is type S (37.5%), in 75% a positive anti-Scl
      70 antibody is present. In mixed connective tissue disease, anti-RNP appears in
      85.7%. In dermatopolymyositis, the anti-Jo-1 antibody is present in 33.3%. In
      undifferentiated connective tissue disease, type S immunofluorescence appears in
      70%. In rheumatoid arthritis the prevailing immunofluorescence is type H
      (homogenous) (46.4%) and type S (speckled) (41.0%), while the presence of ENA is
      rare (anti-Ro/SS-A in 4.6%). In spondylarthritis, type S immunofluorescence
      appears most often (62.5%). Patients with chronic infectious disease,
      malignancies, undefined conditions and degenerative joint disease present with
      various types of immunofluorescence; the presence of ENA is extremely rare in
      these patients. The results of this study underline the significance of ANA and,
      particularly ENA, in the diagnosis of connective tissue disease. These antibodies
      however, can also be identified in various infectious and malignant diseases as
      well as in inflammatory and degenerative joint diseases.

PMID- 9629627
TI  - A case of visceral leishmaniasis in Austria.
AB  - We report a patient aged 41 years with fever of unknown origin. Notable aspects
      of his travel history were a trip to the Philippines and a sailing trip around
      Sicily. The patient presented with fever up to 40 degrees C since 4 weeks,
      weakness, headache, hepatosplenomegaly and night sweat. No specific cause could
      be found. Based on clinical findings tuberculosis was suspected and empirical
      tuberculostatic treatment was started. However, during the following 6 weeks the
      patient's condition deteriorated. A bone marrow biopsy performed to exclude a
      haematological malignancy revealed Leishmania sp. in macrophages. This
      histological diagnosis was confirmed retrospectively by re-examination of a
      previously performed liver biopsy and by an increased anti-leishmania serum
      antibody titer of 1:1280. The patient was treated with sodium stibogluconate
      (pentostam, 850 mg) for 30 days and recovered slowly.

PMID- 9629628
TI  - [Obesity--significance in adolescence and for reproduction].
AB  - According to the actual knowledge obesity is a serious, nutrition-dependent
      pathology with a high number of consequences. Endocrine sequence of obesity such
      as PCO-HAIR-syndrome (polycystic ovarian syndrome, hyperandrogenemia-insulin
      resistance) with its cycle disorders and sterility are beginning already in
      adolescent and women of young reproductive age. With ageing more serious risks
      such as non-insulin dependent diabetes mellitus (NIDDM), arteriosclerosis
      followed by coronary disease, stroke and hypertension, metabolic syndrome and a
      higher prevalence of malignant diseases will appear. Based on these five risks
      obesity should be treated early when therapeutic strategies are more successful
      than in older ages. The definition of a diagnosis and the beginning of a weight
      reduction programme combined with intense motivating treatment as well as medical
      and psychotherapeutic guidance is an important preventive contribution.

PMID- 9629629
TI  - Obesity in female life--from molecular to clinical aspects.
AB  - Obesity gains increasing prevalence world-wide. Multifactorially caused it
      presents itself in numerous heterogeneous phenotypes with a wide spectrum of
      clinical symptoms. The full-blown female obesity syndrome is initiated already in
      childhood, associated with ovarian hyperandrogenaemia (polycystic ovary syndrome)
      in the reproductive phase, and characterised by increasing co-morbidity (cancer;
      metabolic syndrome; arteriosclerosis) in the postmenopausal state leading to
      shortened longevity. Due to the complexity of psychic, somatic and endocrine
      metabolic disturbances a causal break-through in the treatment of the disease
      could not be achieved yet, but the enhanced basal understanding and recently
      investigated pharmaceutical principles might enable to improve the therapeutical
      approaches.

PMID- 9629630
TI  - [Obesity and risk of cancer in the woman].
AB  - Experimental studies in animals and investigations in human beings have
      demonstrated that an increase of body fat mass and the increase of the waist/hip
      ratio raises the risk of endometrial and breast cancer. There are also
      indications for an influence on ovarian and colon cancer. These effects by
      adipose tissue are created by endocrine changes such as an increase of total and
      free estradiol, changes in progesterone secretion, protein binding
      concentrations, growth factors and receptor action. Besides the increased risk
      for cancer there is also an effect on prognosis.

PMID- 9629632
TI  - [Obesity and bone density].

PMID- 9629631
TI  - [Obesity and pregnancy].
AB  - Generally, obesity represents a risk factor for pregnancy and birth. Already the
      conception rate is lowered. If pregnancy occurs, there is an increased abortion
      rate and an increase of neural tube defects. The efficiency of prenatal diagnosis
      is decreased by obesity. In obese women pregnancy is more frequently associated
      with complications such as chronic hypertension, gestosis, disturbances of
      carbohydrate metabolism, liver- and cardiac dysfunction. Central obesity has the
      highest risk probability. Also during birth the risk of complications is
      dependent upon the degree of obesity. This applies to the whole delivery process,
      operative deliveries and the perinatal mortality. Operative delivery by cesarean
      section is associated with a higher complication rate compared with pregnant
      women with normal weight. The postpartal course of body weight has to be
      controlled particularly in obese women.

PMID- 9629633
TI  - [Obesity and thrombotic vascular diseases].
AB  - Obesity may either be unspecific as indicated by an increased body mass index
      (BMI) or due to an abnormal fat-distribution as indicated by an increased waist
      to-hip ratio (WHR). The latter is frequently associated with deteriorations of
      glucose tolerance, hypertriglyceridaemia and hypertension (the metabolic
      syndrome), a syndrome which is among the strongest risk factors of ischemic heart
      disease. It is important to note that visceral obesity is a frequent feature of
      the polycystic ovary syndrome. Also, weight gain after menopause is often
      associated with a particular increase of the WHR. Obesity as indicated by an
      increased BMI (> 30 kg/m2) is a weak but easily detectable risk marker of venous
      thrombotic disease. This risk needs to be considered in clinical practice since
      obesity was shown to enhance the power of precipitating risk factors of venous
      disease such as pregnancy, surgery or estrogen treatment.

PMID- 9629634
TI  - [Psychosomatic aspects of obesity].
AB  - Obesity is characterised by an imbalance of caloric intake and energy
      expenditure. Increased caloric uptake and reduced physical activity are
      important. No specific psychopathology exists in obesity. Obese people view their
      body weight and form significantly more negative than lean controls and often
      experience depression and anxiety. Quality of life is often impaired. Obesity
      causes many disadvantages in interpersonal and social aspects. 30% of the obese
      subjects report binge eating. Whether binge eating should be considered as an
      independent syndrome is currently under discussion. The treatment of obesity is
      not satisfactory. Pharmacological approaches have so far failed. Behavioral
      therapy including dieting of different forms is not successful in long terms. 95%
      of the patients regain body weight within five years. Surgical therapy are very
      successful but should be only applied in severe obesity.

PMID- 9629635
TI  - Nonparametric estimation of covariance structure in longitudinal data.
AB  - In longitudinal studies, the effect of various treatments over time is usually of
      prime interest. However, observations on the same subject are usually correlated
      and any analysis should account for the underlying covariance structure. A
      nonparametric estimate of the covariance structure is useful, either as a guide
      to the formulation of a parametric model or as the basis for formal inference
      without imposing parametric assumptions. The sample covariance matrix provides
      such an estimate when the data consist of a short sequence of measurements at a
      common set of time points on each of many subjects but is impractical when the
      data are severely unbalanced or when the sequences of measurements on individual
      subjects are long relative to the number of subjects. The variogram of residuals
      from a saturated model for the mean response has previously been suggested as a
      nonparametric estimator for covariance structure assuming stationarity. In this
      paper, we consider kernel weighted local linear regression smoothing of sample
      variogram ordinates and of squared residuals to provide a nonparametric estimator
      for the covariance structure without assuming stationarity. The value of the
      estimator as a diagnostic tool is demonstrated in two applications, one to a set
      of data concerning the blood pressure of newborn babies in an intensive care unit
      and the other to data on the time evolution of CD4 cell numbers in HIV
      seroconverters. The use of the estimator in more formal statistical inferences
      concerning the mean profiles requires further study.

PMID- 9629636
TI  - Problems with determination of noncommunicating classes for Monte Carlo Markov
      chain applications in pedigree analysis.
AB  - Exact calculations for probabilities on complex pedigrees are computationally
      intensive and very often infeasible. Markov chain Monte Carlo methods are
      frequently used to approximate probabilities and likelihoods of interest.
      However, when a locus with more than two alleles is considered, the underlying
      Markov chain is not guaranteed to be irreducible and the results of such analyses
      are unreliable. A method for finding the noncommunicating classes of the Markov
      chain would be very useful in designing algorithms that can jump between these
      classes. In this paper, we will examine some existing work on this problem and
      point out its limitations. We will also comment on the difficulty of developing a
      useful algorithm.

PMID- 9629638
TI  - Regression modelling of diagnostic likelihood ratios for the evaluation of
      medical diagnostic tests.
AB  - The use of diagnostic likelihood ratios has been advocated in the epidemiologic
      literature for the past decade. Diagnostic likelihood ratios provide valuable
      information about the predictive properties of a diagnostic test while having the
      attractive feature of being independent of the prevalence of disease in the study
      population. We propose a new regression method that allows for direct assessment
      of covariate effects on likelihood ratios for binary diagnostic tests. This may
      be particularly useful in assessing how factors that are under the control of the
      clinician can be altered to maximize the predictive ability of the test.
      Similarly, patient characteristics that influence the ability of the test to
      discriminate between diseased and nondiseased subjects may be identified using
      the regression model. The regression method is flexible in that it can
      accommodate clustered data arising from a variety of study designs. We illustrate
      the method with data from an audiology study.

PMID- 9629637
TI  - Likelihood-based inference for the genetic relative risk based on affected
      sibling-pair marker data.
AB  - Using genetic marker data from affected sibling pairs, we study likelihood-based
      linkage analysis under quasi-recessive, quasi-dominant, and general single-locus
      models. We use an epidemiologic parameterization under a model where the marker
      locus is closely linked to the putative disease susceptibility gene. This model
      and parameterization allow inferences about the relative risk associated with the
      susceptible genotype. We base inferences on approximate likelihoods that focus on
      the affected siblings in the sibship and, using these likelihoods, we derive
      closed-form maximum likelihood estimators for model parameters and closed-form
      likelihood ratio statistics for tests that the relative risk associated with the
      susceptible genotype is one. Under the general single-locus model, our likelihood
      ratio test is the same as the iteratively computed triangle test proposed by
      Holmans (1993, American Journal of Human Genetics 52, 362-374) for the case where
      marker identity-by-descent is known; our derivation gives a closed form for the
      test statistic. We present quartiles of the distribution of parameter estimates
      and critical values for the exact null distribution of our likelihood ratio test
      statistics; we also give large-sample approximations to their null distributions.
      We show that the powers of our likelihood ratio tests exceed the powers of more
      commonly used nonparametric affected-sibling-pair tests when the data meet the
      inheritance model assumptions used to derive the test; we also show that our
      tests' powers are robust to violation of model assumptions. We conclude that our
      model-based inferences provide a practical alternative to more common affected
      sibling-pair tests when investigators have some knowledge about the mode of
      inheritance of a disease and that our methods may sometimes be useful for
      comparing the genetic relative risk with environmental relative risks.

PMID- 9629639
TI  - Comparing correlated areas under the ROC curves of two diagnostic tests in the
      presence of verification bias.
AB  - To assess relative accuracies of two diagnostic tests, we often compare the areas
      under the receiver operating characteristic (ROC) curves of these two tests in a
      paired design. Standard methods for analyzing data from a paired design require
      that every patient tested has the known disease status. In practice, however,
      some of the patients with test results may not have verified disease status. Any
      analysis using only verified cases may result in verification bias. In this
      paper, we propose a verification bias correction procedure for comparing areas
      under ROC curves under the missing-at-random (MAR) assumption. We also develop an
      approach for testing the validity of the MAR assumption. Finally, we use the
      proposed method to compare the relative accuracies of MRI and CT in evaluation of
      pancreatic cancer.

PMID- 9629640
TI  - A mixed model for repeated dilution assays.
AB  - We propose a generalized linear mixed model to estimate and test marginal effects
      on titers repeatedly measured by serial dilution assays. The link is log-log and
      the titer is assumed to follow a gamma distribution. The parameters are estimated
      by generalized estimating equations. The marginal effects are tested by means of
      Wald and score tests, using the robust estimator of the variance. This approach
      avoids the problems arising from assays leading to nonestimable individual
      titers. Simulations were used to compare the Wald and score tests to Wilcoxon and
      Student t-tests. This method is applied to the comparison of the antiviral
      efficiency of three treatments against HIV.

PMID- 9629641
TI  - Time series analysis of Aplysia total motion activity.
AB  - We rely on various nonparametric time series techniques to quantify several
      autocorrelated Aplysia total motion activity series. The effect of light on total
      motion activity has been removed. A general model will be proposed for total
      motion activity, which is found to display a circadian rhythm, and the toxic
      effect of PCBs on total motion activity will be assessed. No underlying
      assumptions are made about the form of the circadian rhythm. Several types of
      circadian total motion activity patterns are discovered. We form the hypothesis
      that different data series may be separated into three distinct groups of common
      patterns of circadian total motion activity. We also investigate if in fact only
      a single innate oscillator regulates total motion activity.

PMID- 9629642
TI  - Evaluating agreement with a gold standard in method comparison studies.
AB  - We develop a statistical model for method comparison studies where a gold
      standard is present and propose a measure of agreement. This measure can be
      interpreted as a population correlation coefficient in a constrained bivariate
      model. An estimator of this coefficient is proposed and its statistical
      properties explored. Applications of the new methodology to data from the medical
      literature are presented.

PMID- 9629643
TI  - Discrete distributions for use in twin studies.
AB  - We describe several new discrete distributions motivated by the study of
      longevity in twins. All individuals both living and dead at a given age are
      randomly paired. The univariate distribution models the number of these pairs
      where both individuals are alive. If there is a positive association to longevity
      in twins, then we would expect to see an excessive number of twin pairs both
      alive at older ages relative to the number of living individuals. We obtain
      Poisson and normal approximations to the exact distribution. Multivariate
      distributions are developed to allow for simultaneous and conditional inference
      at different ages. Odds-ratio parameter models provide a measure of the
      association of longevity within twin pairs. These models indicate an excessive
      number of identical twin pairs both alive after age 60 in a cohort of twins born
      between 1870 and 1880 in Denmark. Monozygotic twins are contrasted with dizygotic
      twins to separate the genetic and environmental contributions to the similarity
      in longevity among twins.

PMID- 9629644
TI  - Dose-dependent number of implants and implications in developmental toxicity.
AB  - This paper proposes a method for assessing risk in developmental toxicity studies
      with exposure prior to implantation. The method proposed in this paper was
      developed to account for a dose-dependent trend in the number of implantation
      sites per dam, which is a common problem in studies with exposure prior to
      implantation. Toxins may have the effect of interfering with the early
      reproductive process, which can prevent implantation in the uterine wall. An
      imputation procedure is presented for estimating the number of potential fetuses
      by sampling from the empirical distribution of the number of implants per litter
      in the control group. The marginal death outcomes and the joint malformation and
      survival outcomes for each potential fetus can be estimated using multiple
      imputation or the chained data augmentation algorithm. Logit models can then be
      fit and used to estimate the effect of dose on reducing the probability of a
      normal birth. These models accommodate multiple covariate effects and can be
      applied to low-dose extrapolation. A simulation study is done to evaluate the
      properties of model-based estimators of the mean response and the virtually safe
      dose level (VSD). It was found that both estimates were good approximations of
      the underlying dose effect. A dominant lethal assay data set (Luning et al.,
      1966, Mutation Research 3, 444-451) is analyzed, and the results are compared
      with those of Rai and Van Ryzin.

PMID- 9629645
TI  - Local influence in linear mixed models.
AB  - The linear mixed model has become an important tool in modelling, partially due
      to the introduction of the SAS procedure MIXED, which made the method widely
      available to practising statisticians. Its growing popularity calls for data
      analytic methods to check the underlying assumptions and robustness. Here, the
      problem of detecting influential subjects in the context of longitudinal data is
      considered, following the approach of local influence proposed by Cook.

PMID- 9629646
TI  - Bidirectional case-crossover designs for exposures with time trends.
AB  - In the case-crossover design (Maclure, 1991, American Journal of Epidemiology
      133, 144-153), only cases are sampled, and risk estimates are based on within
      subject comparisons of exposures at failure times with exposures at times prior
      to failure, using matched case-control methods. While the design provides
      considerable advantages, unidirectional retrospective control sampling (selecting
      control times only prior to failure) can cause risk estimates to be confounded by
      time trends in exposure. However, when subsequent exposures are not influenced by
      failures, as in studies of environmental exposures such as air pollutants, it is
      possible to determine at times postfailure what a subject's level of exposure
      would have been had the subject not failed. We describe a bidirectional case
      crossover design in which exposures at failure are compared with exposures both
      before and after failure. Simulation analyses show that relative risk estimates
      are resistant to confounding by time trend. We also extend the method to studies
      involving multiple failure times.

PMID- 9629647
TI  - Between- and within-cluster covariate effects in the analysis of clustered data.
AB  - Standard methods for the regression analysis of clustered data postulate models
      relating covariates to the response without regard to between- and within-cluster
      covariate effects. Implicit in these analyses is the assumption that these
      effects are identical. Example data show that this is frequently not the case and
      that analyses that ignore differential between- and within-cluster covariate
      effects can be misleading. Consideration of between- and within-cluster effects
      also helps to explain observed and theoretical differences between mixture model
      analyses and those based on conditional likelihood methods. In particular, we
      show that conditional likelihood methods estimate purely within-cluster covariate
      effects, whereas mixture model approaches estimate a weighted average of between-
      and within-cluster covariate effects.

PMID- 9629648
TI  - Clinical trial designs based on sequential conditional probability ratio tests
      and reverse stochastic curtailing.
AB  - We propose a group sequential method based on the sequential conditional
      probability ratio test and show that it has the conservatism desired in practice.
      We also propose calculating the discordant probability, that is, the probability
      that the sequential test concludes differently from a fixed-sample test at the
      planned end of the trial, recognizing that this probability could be substantial,
      even if the sequential test has the same size and power as the fixed-sample size
      test at the planned end of the study. In addition, we show that the proposed
      method can be used as a stochastic curtailing tool. Thus, the method accommodates
      unplanned interim analyses as well as those deemed necessary based on data
      trends, virtually without inflating the type I error, but it is less conservative
      than the usual stochastic curtailing. The method is implemented through an
      interactive computer program.

PMID- 9629650
TI  - Interval estimation of the risk ratio between a secondary infection, given a
      primary infection, and the primary infection.
AB  - This paper discusses interval estimation of the risk ratio (RR) between a
      secondary infection, given a primary infection, and the primary infection. Three
      asymptotic closed-form interval estimators are developed using Wald's test
      statistic, the logarithmic transformation, and Fieller's theorem. The performance
      of these interval estimators is compared with respect to the coverage probability
      and the expected length of the resulting confidence intervals. When the
      underlying probability of a primary infection is high (say, 0.80), all three
      estimators perform reasonably well. In fact, in this case, they are all
      essentially equivalent when the number of subjects n > or = 100. When the
      probability of a primary infection is small (say, 0.20) or moderate (say, 0.30 to
      0.50), the interval estimator using the logarithmic transformation outperforms
      the other two estimators when n < or = 100. In fact, the coverage probability of
      the former estimator is consistently greater than or equal to the desired
      confidence level in all the situations considered in this paper and hence is
      recommended for general use.

PMID- 9629649
TI  - A comparison of two methods for adaptive interim analyses in clinical trials.
AB  - Recently, two methods for planning and conducting two-stage procedures were
      proposed (Bauer and Kohne, 1994, Biometrics 50, 1029-1041; Proschan and
      Hunsberger, 1995, Biometrics 51, 1315-1324). Both procedures allow the
      termination of the trial with the early acceptance of H0 in the absence of a
      treatment effect after performing the first stage of the study. Furthermore, the
      observed treatment effect at stage I can be used for planning and redesigning the
      second stage of the study in a way that protects the Type I error rate. The exact
      Type I error rate of the Proschan and Hunsberger approach is derived. It is shown
      that the two methods lead to similar decision rules with negligibly small
      differences in power and expected sample size. In terms of providing design tools
      and practical applicability, however, they differ. The practical performance of
      the procedures is discussed and recommendations for their use are given.

PMID- 9629651
TI  - Modelling time-dependent interaction in a time-varying covariate and its
      application to rejection episodes and kidney transplant failure.
AB  - Acute rejection episodes are thought to be prognostic of eventual kidney graft
      failure. The influence of rejection events on the hazard of transplant failure
      appears to be a complex function of how long after transplantation the rejection
      event occurs as well as the time elapsed since the rejection event. To examine
      the nature of this relationship, we propose a penalized likelihood approach to
      estimate the parameters of a two-dimensional rectanglewise constant hazard model.
      The approach appears to be fairly successful at modelling time dependency in a
      time-varying covariate. The approach is equally applicable for modelling fixed
      covariates that act in a jointly nonproportional (non-log-linear) and time
      dependent manner.

PMID- 9629652
TI  - Goodness-of-fit tests for GEE modeling with binary responses.
AB  - Analysis of data with repeated measures is often accomplished through the use of
      generalized estimating equations (GEE) methodology. Although methods exist for
      assessing the adequacy of the fitted models for uncorrelated data with likelihood
      methods, it is not appropriate to use these methods for models fitted with GEE
      methodology. We propose model-based and robust (empirically corrected) goodness
      of-fit tests for GEE modeling with binary responses based on partitioning the
      space of covariates into distinct regions and forming score statistics that are
      asymptotically distributed as chi-square random variables with the appropriate
      degrees of freedom. The null distribution and the statistical power of the
      proposed goodness-of-fit tests were assessed using simulated data. The proposed
      goodness-of-fit tests are illustrated by two examples using data from clinical
      studies.

PMID- 9629653
TI  - Estimating the transmission rate for a highly infectious disease.
AB  - It is pointed out that estimates of disease transmission parameters based on the
      final size of an epidemic are unsatisfactory when all susceptibles are infected
      and that this is an event with a substantial probability for communities of
      practical interest. We propose a method for estimating the transmission rate for
      such highly infectious diseases under the assumptions that the removal process of
      the disease is fully observed and that the mean duration of the infectious period
      is known. The method uses smoothed differentiation of the removal process. A
      simulation study shows that the method performs satisfactorily.

PMID- 9629654
TI  - Investigations of the problems of assessing aflatoxin levels in peanuts.
AB  - In this study, a number of probability distributions that have been used to model
      the occurrence of aflatoxin in peanuts are compared. Two distributions, the
      compound gamma and the negative binomial, are shown to have special appeal in
      that both can be justified by reasoning from the fundamental biological and
      stochastic processes that generate the aflatoxin. Since method of moments and
      maximum likelihood give consistent estimates of parameters in both models,
      practical considerations suggest using the former. One hundred twenty data sets,
      each consisting of fifty observations, were not sufficient to provide goodness-of
      fit tests to establish either as superior to the other as a model. Both models
      fit the data well, appreciably better than other models examined. An attractive
      aspect of the compound gamma and the negative binomial distributions is that, as
      a consequence of their theoretical underpinnings, both involve parameters that
      have meaningful interpretations. In the compound gamma, the alpha parameter
      reflects the shape of the kernel-to-kernel aflatoxin content distribution, the
      lambda parameter reflects the number (or frequency) of contaminated kernels in
      the sample, and the beta parameter is a scale parameter. In the negative
      binomial, the two parameters can be used as measures of mean or location and
      shape.

PMID- 9629655
TI  - Testing for trend with count data.
AB  - Among the tests that can be used to detect dose-related trends in count data from
      toxicological studies are nonparametric tests such as the Jonckheere-Terpstra and
      likelihood-based tests, for example, based on a Poisson model. This paper was
      motivated by a data set of tumor counts in which conflicting conclusions were
      obtained using these two tests. To define situations where one test may be
      preferable, we compared the small and large sample performance of these two tests
      as well as a robust and conditional version of the likelihood-based test in the
      absence and presence of a dose-related trend for both Poisson and overdispersed
      Poisson data. Based on our results, we suggest using the Poisson test when little
      overdispersion is present in the data. For more overdispersed data, we recommend
      using the robust Poisson test for highly discrete data (response rate lower than
      2-3) and the robust Poisson test or the Jonckheere-Terpstra test for moderately
      discrete or continuous data (average responses larger than 2 or 3). We also
      studied the effects of dose metameter misspecification. A clear effect on
      efficiency was seen when the 'wrong' dose metameter was used to compute the test
      statistic. In general, unless there is strong reason to do otherwise, we
      recommend the use of equally spaced dose levels when applying the Poisson or
      robust Poisson test for trend.

PMID- 9629656
TI  - Adjustment of cancer incidence rates for ethnic misclassification.
AB  - Although ethnic population counts measured by the United States Census are based
      on self-identification, the same is not necessarily true of cases reported to
      cancer registries. The use of different ethnic classification methods for
      numerators and denominators may therefore lead to biased estimates of cancer
      incidence rates. The extent of such misclassification may be assessed by
      conducting an ethnicity survey of cancer patients and estimating the proportion
      misclassified using double sampling models that account for sample
      stratification. For two ethnic categories, logistic regression may be used to
      model self-identified ethnicity as a function of demographic variables and the
      fallible classification method. Incidence rates then may be adjusted for
      misclassification using regression results to estimate the number of cancer cases
      of a given age, sex, and site in each self-identified ethnic group. An example is
      given using this method to estimate ethnic misclassification of San Francisco Bay
      area Hispanic cancer patients diagnosed in 1990. Results suggest that the number
      of cancer cases reported as Hispanic is an underestimate of the number of cases
      self-identified as Hispanic, resulting in an underestimate of Hispanic cancer
      rates.

PMID- 9629657
TI  - A calnaktin-like inhibitor of Na,K-ATPase in rat brain: regulation of alpha 1 and
      alpha 2 isozymes.
AB  - This study was designed to determine if a Ca(2+)-dependent, calnaktin-like
      inhibitor of Na,K-ATPase existed in rat brain and to compare the inhibition of
      different Na,K-ATPase isozymes in brain, heart and kidney. Based on the size and
      characteristics of human red blood cell calnaktin, a soluble protein fraction was
      obtained from rat brain and subjected to ultrafiltration and gel filtration to
      restrict the proteins to an appropriate molecular range of 6-50 kDa (6/50
      fraction) for a crude calnaktin preparation. The 6/50 fraction was reconstituted
      with semipurified rat brain Na,K-ATPase and resulted in Ca(2+)-dependent
      inhibition of Na,K-ATPase activity. A 6/50 fraction was also prepared from rat
      heart ventricles, and, in its presence, Ca(2+)-dependent inhibition of cardiac
      Na,K-ATPase activity was observed. With brain preparations, the threshold for
      inhibition was approximately 100 nM free Ca2+, and inhibition was half maximal at
      3-10 microM free Ca2+. Different isozymes of Na,K-ATPase were examined using
      differential sensitivity to ouabain and differential tissue distribution in
      brain, heart and kidney. The alpha 1 activity was inhibited in all three tissues.
      The alpha 2 activity of heart and the alpha 2 and/or alpha 3 activity of brain
      were also inhibited by the brain 6/50 fraction. In synaptosomal preparations from
      rat forebrain, resting intracellular (intrasynaptosomal) free Ca2+ was close to
      the threshold for calnaktin-like inhibition. The results are consistent with the
      presence of a calnaktin-like inhibitor of Na,K-ATPase in rat brain and indicate
      that calnaktin could be a widespread regulator of the alpha 1 isozyme. In
      addition, this study provides the first evidence that calnaktin also inhibits the
      alpha 2 activity of heart and the alpha 2 and/or alpha 3 isozymes of brain.

PMID- 9629658
TI  - Effects of soy protein on plasma cholesterol and bile acid excretion in hamsters.
AB  - The effect of dietary casein and soy protein on lipoprotein metabolism was
      compared in the Golden Syrian hamster (Mesocricetus auratus). Total plasma
      cholesterol was similar in animals fed either protein, but significant
      differences were seen in lipoprotein profile. In animals fed soy protein,
      cholesterol concentrations were lower in very-low-density lipoproteins (VLDL) but
      higher in low-density and high-density lipoproteins, compared with those fed
      casein. Significant differences were also seen depending on the nutritional state
      of the animals. In casein-fed hamsters, total plasma triacylglycerol and
      chylomicron + VLDL cholesterol and triacylglycerol were significantly higher when
      blood was collected during feeding, compared with animals that had been fasted
      overnight. By contrast, no significant change was seen in animals on the soy
      protein diet. This suggests that either intestinally derived lipoproteins are
      more rapidly cleared on the soy protein diet or that soy inhibits feeding-induced
      VLDL secretion. Fecal bile acid excretion was higher in the soy protein group,
      and there was a significant correlation between soy intake and bile acid
      excretion. Hepatic cholesterol decreased as the amount of soy protein consumed
      increased, suggesting that it is this pool of cholesterol that is used to replace
      the excreted bile acids. No significant difference was seen in plasma insulin or
      glucagon between hamsters fed the two proteins. Plasma triiodothyronine
      concentrations were, however, significantly higher and thyroxine concentrations
      lower in the soy protein-fed animals. This study shows specific effects of
      dietary proteins on plasma lipoprotein concentrations dependent on nutritional
      status of the animal.

PMID- 9629659
TI  - Pregnancy-associated adaptations to hepatic phosphatidylcholine biosynthesis in
      the guinea-pig.
AB  - Pregnancy is associated with increased phosphatidylcholine (PC) 16:0/22:6 and
      PC16:0/20:4 concentrations in rat liver and plasma, guinea-pig liver, and in
      plasma in women. These changes may be related to supply of polyunsaturated fatty
      acids (PUFA) to the fetus. For the rat, these adaptations to hepatic PC
      composition are regulated by modifications to synthesis de novo from choline.
      However, it is not known whether these adaptations are applicable to other
      species. Consequently, we have determined biochemical mechanisms for regulation
      of hepatic PC synthesis in the pregnant guinea pig. The PUFA content of guinea
      pig liver PC synthesised de novo did not change significantly during pregnancy.
      [Methyl-14C]methionine incorporation into PC in vivo, however, showed increased
      PC16:0/22:6 and PC16:0/20:4 contents. [Methyl-14C]methionine incorporation into
      PC over 6 hr in vivo increased during early pregnancy, while PC synthesis de novo
      did not change. In contrast to the rat, modulation of PE N-methylation is a
      primary mechanism for regulating the PUFA content of hepatic PC in the pregnant
      guinea-pig. The use of distinct metabolic strategies to achieve comparable
      pregnancy-associated adaptations to hepatic PC composition between these animal
      species suggests both evolutionary convergence and a fundamental the role for
      PC16:0/22:6 and PC16:0/20:4 in PUFA metabolism during gestation.

PMID- 9629660
TI  - Purification and characterization of a new potential in vivo inhibitor of
      cathepsin L from bovine skeletal muscle.
AB  - Four papain-inhibiting peaks, labeled F-I, F-II, F-III, and F-IV, were
      fractionated from a crude bovine muscle extract by gel filtration chromatography
      on Sephadex G100, and the F-III fraction was analyzed. From F-III, a cysteine
      proteinase inhibitor was purified by two successive anionic exchange
      chromatography steps on Q-Sepharose and Mono-Q columns. This inhibitor has a
      molecular weight of about 30 kDa. Regarding its specificity toward different
      proteinases, the purified 30 kDa inhibitor was inactive against serine (trypsin
      and chymotrypsin) and aspartyl (pepsin) families. In contrast, cathepsin L, H, B,
      and papain, four enzymes of the cysteine class were strongly inhibited suggesting
      that this inhibitor was specific to the cysteine proteinase group. However, no
      inhibitory activity was shown against calpains. Kinetic parameters, including
      inhibition constants (Ki), rate constant for association (kass) and time required
      for almost complete inhibition of proteinase in vivo were determined. The values
      are consistent with a possible physiological function for this inhibitor protein
      in controlling in vivo cathepsin L activity.

PMID- 9629661
TI  - The CP-I subunit of adenosine deaminase complexing protein from calf kidney is
      identical to human, mouse, and rat dipeptidyl peptidase IV.
AB  - The CP-I subunit of calf kidney adenosine deaminase complexing protein (ADCP),
      isolated by affinity chromatography based on Sepharose-4B immobilized adenosine
      deaminase, is identical with dipeptidyl peptidase IV. This finding is based on
      the following results: (a) Its M(r) = 110 kD, as determined by sodium dodecyl
      sulphate polyacrylamide gel electrophoresis; (b) its catalytic activity toward
      Gly-Pro-p-nitroanilide; (c) its inhibition by serine protease inhibitor; and (d)
      by two peptide sequences resulting from its trypsin proteolysis. Accordingly, the
      CP-I subunit of ADCP isolated from bovine kidney is DPPIV (CD26). Thus, as
      anticipated, the high affinity between ADA subunits prevails even when they
      originate in different species.

PMID- 9629662
TI  - The occurrence of Iso 24:0 (22-methyltricosanoic acid) fatty acid in
      sphingomyelin of rat tissues.
AB  - The occurrence of an unusual fatty acid, iso 24:0 (22-methyltricosanoic acid),
      has been shown to be present in the sphingomyelin from rat liver by gas liquid
      chromatography-mass spectrometry. The fatty acid is also present in the
      sphingomyelin of rat tissues tested, except for brain and fetal serum.
      Supplementation of diets with L-valine elevated the content of iso 24:0 in rat
      liver, heart, and kidney sphingomyelin. The fatty acid appears to be present in
      sphingomyelin of the sera of mice, dogs, and cats, but not humans.

PMID- 9629664
TI  - Influence of lipid profile and fatty acid composition on the oxidation behavior
      of rat and guinea pig low density lipoprotein.
AB  - Low density lipoprotein (LDL) oxidation is one of the first steps proposed for
      the development of atherosclerosis. Since lipid profile and fatty acid
      composition may affect this process, we studied the influence of these factors on
      the oxidation behavior of rat and guinea pig LDL. Marked compositional
      differences were observed. Thus, the main lipid carried by rat LDL was
      triglyceride (TG) (35.8 +/- 5.8%, w/w) whereas total cholesterol (TC) represented
      23.8 +/- 3.0%. In contrast, guinea pig LDL contained 13.2 +/- 2% of TG and 44.8
      +/- 4.5% of TC. Rat LDL contained higher 20:4(n-6) molar percentages than guinea
      pig LDL. Thiobarbituric acid reactive substances (TBARS) production (255 +/- 26
      and 137 +/- 13 nmol malondialdehyde/mg prot. for rat and guinea pig LDL,
      respectively) and the maximum rate of conjugated dienes (CD) formation (485 +/-
      93 and 77 +/- 11 nmol CD/min/mg protein for rat and guinea pig LDL, respectively)
      showed that rat LDL are less resistant to oxidation in vitro than guinea pig LDL.
      The higher oxidation rate of rat LDL seems to be related to its lipid profile,
      mainly to the high proportion of TG, and to the high content of 20:4(n-6), which
      is one of the fatty acids most prone to oxidation.

PMID- 9629663
TI  - Alteration of redox stability of hemoglobins A and S by biological buffers.
AB  - Several organic and inorganic buffers, including Hepes, Tris and potassium
      phosphate, are often used for the maintenance of pH in hemoglobin solution work.
      It has often been assumed these buffers do not significantly affect the solution
      stability of these proteins. This investigation has focused on the effect these
      buffers have on the redox stability of the heme-iron, [Fe+2-->Fe+3], of
      hemoglobins A and sickle cell S (beta 6 glu-->val) over extended periods of time.
      Initial results indicate that: 1) the use of different buffers under similar
      ionic strength conditions at pH 7.0 affect conformational changes that produce
      substantial differences in redox stability between Hb A and Hb S; 2) spectral
      analysis of these hemoglobins in the visible region (700-500 nm) at 37 degrees C
      for extended periods of time indicated that a slower rate of autoxidation is
      observed with a Hepes buffered system over a wide ionic strength range than for
      either Tris or potassium phosphate buffers; 3) Hb S autoxidized at a faster rate
      in the presence of each of these buffers than Hb A; and 4) in contrast to Hb A,
      Hb S showed extensive hemichrome formation after 15 hr in the presence of
      potassium phosphate buffer.

PMID- 9629665
TI  - The catalytic subunits of Ser/Thr protein phosphatases from Caenorhabditis
      elegans.
AB  - The catalytic activities of protein phosphatase 1, 2A, 2B, and 2C were detected
      in crude extracts of Caenorhabditis elegans with different phosphoprotein
      substrates and specific inhibitors or activators. The enzymological properties of
      protein phosphatase 2B as well as those of the catalytic subunits of protein
      phosphatase 1 and protein phosphatase 2A were determined after partial
      purification. Gene fragments encoding the catalytic subunits of the protein
      phosphatase 1-2A-2B superfamily were amplified by polymerase chain reaction and
      were identified by DNA sequencing. Besides the homologs of protein phosphatase 1,
      2B, and X, five protein phosphatase 1-type sequences and four novel protein
      phosphatase sequences were found. Our data, together with the results of the C.
      elegans genome project, suggest that this nematode contains an extensive family
      of Ser/Thr specific protein phosphatases including several up to now
      biochemically uncharacterized members.

PMID- 9629666
TI  - The proton permeability of the inner membrane of liver mitochondria from
      ectothermic and endothermic vertebrates and from obese rats: correlations with
      standard metabolic rate and phospholipid fatty acid composition.
AB  - We measured the proton leak across the inner membrane of liver mitochondria
      isolated from six different vertebrate species and from obese and control Zucker
      rats. Proton leak at 37 degrees C was similar in rat and pigeon, and in obese and
      control Zucker rats. Compared to rat, it was lower in cane toad, shingleback
      lizard, and the Madeiran lizard Lacerta dugessi. Proton leak at 20 degrees C was
      similar in xenopus toad and higher in rainbow trout, compared to rat. In general,
      proton permeability and substrate oxidation activity were greater in liver
      mitochondria from endotherms than those from ectotherms. Analysis of this and
      previous data showed that proton leak per milligram of mitochondrial protein
      correlated with standard metabolic rate, and proton leak per milligram of inner
      membrane phospholipid correlated with 11 phospholipid fatty acid compositional
      parameters, including unsaturation index.

PMID- 9629667
TI  - Cross reactivities among some mammalian haptoglobins studied by a monoclonal
      antibody.
AB  - Mouse monoclonal antibody antihuman-Hp, product of clone 2.36.71.41 was found to
      recognize, however, with different affinities, the immunological determinant on
      haptoglobin of some mammals (goat, sheep, cow, horse, rabbit). The following
      differences in immunological cross reactivities were noticed: (i) haptoglobins
      present in sera of goat, sheep and cow (Artiodactyla, Bovidae) react in enzyme
      linked immunosorbent assay (ELISA) and form precipitates in agarose gel; (ii)
      horse (Perissodactyla) and rabbit (Lagomorpha) haptoglobins react in ELISA, but
      they do not form precipitates; and (iii) haptoglobins of dog, fox, cat
      (Carnivora) and pig (Artiodactyla, Suidae) are not recognized by the tested
      monoclonal antibody either in ELISA or in agarose gel. This study suggests that
      monoclonal antibody, clone 2.36.71.41, recognizes the structure on haptoglobin
      around the disulphide bond linking two alpha chains. Antigenic structure of
      Bovidae haptoglobins is rather similar to human haptoglobin 2-2 (circular
      polymers) than to 2-1 type (linear polymers). Monoclonal antibody 2.36.71.41
      could be used for classification of mammalian haptoglobins by epitope structure.
      It can distinguish polymeric haptoglobins similar to human type 2-2 from other
      mammalian haptoglobins.

PMID- 9629668
TI  - A new attempt to assess the effect of learning processes on the cholinergic
      system: studies on fruitflies and honeybees.
AB  - The effect of training on the functioning of the cholinergic system was
      investigated in fruitflies and in honeybees. Drosophila were submitted to a
      passive avoidance conditioning of the proboscis extension response (PER). Flies
      had to learn to suppress the sugar-induced PER to avoid an aversive quinine
      reinforcement. In a yoked control group, the punishment was administered with no
      relation to the response displayed. Honeybees underwent a five-trial olfactory
      conditioning of the PER elicited by an antennal gustatory stimulation. In the
      control group, olfactory and gustatory stimulations were unpaired to prevent a
      learning process from developing. Immediately at the end of the learning session,
      acetylcholinesterase (AChE) activity was individually measured on the whole
      animal for Drosophila and on the head for the honeybee in experimental and in
      control groups. In fruitflies and honeybees, the AChE rate did not differ between
      the experimental group and its respective control group. Moreover, no significant
      correlation could be found individually between the learning performance and the
      AChE rate in either Drosophila or in honeybees. This experiment did not reveal
      any modulatory effect of the learning acquisition level on the AChE activity in
      insects as was previously reported in honeybees.

PMID- 9629670
TI  - Cloning and sequencing of cDNA encoding haptoglobin, an acute phase protein in
      Syrian hamster, Mesacricetus auratus.
AB  - One of the most prominent acute phase proteins in Syrian hamster (Mesacricetus
      auratus) was identified as haptoglobin and cDNA encoding this protein was
      sequenced. The deduced amino acid sequence of the mature protein is 83.6, 80.5,
      79.6, and 76.1% identical to those of mouse, rat, human (1 s isoform), and dog
      homologues, respectively. As compared with six known members of this family,
      including human haptoglobin-related protein, hamster haptoglobin had 11 unique
      substitutions and one unique codon deletion, that is, the corresponding residues
      have been conserved in all other members. This indicates that hamster haptoglobin
      gene has accumulated these unique mutations after the time of cricetid-murid
      split while the ancestral sequence has been conserved in all other species
      examined. Hamster haptoglobin, however, contains nine cysteine residues, all of
      which are found in conserved positions in primate and rodent homologues.
      Molecular phylogenetic trees of alpha- and beta-chains show that the alpha-chain
      is more divergent than the beta-chain and that the difference in genetic distance
      between canine and hamster alpha-chains is much greater than that of
      corresponding beta-chains.

PMID- 9629669
TI  - The porcine acute phase response to infection with Actinobacillus
      pleuropneumoniae. Haptoglobin, C-reactive protein, major acute phase protein and
      serum amyloid A protein are sensitive indicators of infection.
AB  - In an experimental infection model mimicking acute Actinobacillus
      pleuropneumoniae (Ap) infection in swine (Sus scrofa) by aerosol inoculation, the
      development of a number of typical clinical signs was accompanied by a prototypic
      acute phase reaction encompassing fever and an acute phase protein response
      peaking at around 2 days after infection. Haptoglobin, C-reactive protein (CRP),
      and major acute phase protein (MAP) responded with large increases in serum
      levels, preceding the development of specific antibodies by 4-5 days. Serum
      amyloid A protein (SAA) was also strongly induced. The increase, kinetics of
      induction and normalization were different between these proteins. It is
      concluded that experimental Ap-infection by the aerosol route induces a typical
      acute phase reaction in the pig, and that pig Hp, CRP, MAP, and SAA are major
      acute phase reactants. These findings indicate the possibility of using one or
      more of these reactants for the nonspecific surveillance of pig health status.

PMID- 9629671
TI  - Heat-shock-induced assembly of Hsp30 family members into high molecular weight
      aggregates in Xenopus laevis cultured cells.
AB  - In this study, we have examined whether members of the small heat shock protein
      family, hsp 30, were capable of forming heat-induced aggregates in Xenopus laevis
      A6 kidney epithelial cells. Rate-zonal centrifugation coupled with immunoblot
      analysis demonstrated the presence of hsp30 aggregates with an estimated
      sedimentation coefficient of 10-16S. Also, pore exclusion limit electrophoretic
      analysis of labeled protein from heat-shocked A6 cells revealed four heat-induced
      aggregates, including a prominent 510 kDa aggregate, as well as weaker 350, 290,
      and 240 kDa aggregates. Immunoblot analysis of the aggregates employing an hsp30C
      antibody suggested that the 510 and 350 kDa aggregates were comprised of hsp30
      protein. One- and two-dimensional SDS-PAGE analysis of the proteins isolated from
      the 510 kDa region of the pore exclusion limit electrophoretic gel confirmed the
      presence of 30 kDa heat-induced protein. A total of eight small hsps were present
      in this aggregate, suggesting that virtually all of the major small hsps in
      Xenopus A6 cells were involved in aggregate formation. This study also detected
      the presence of heat-inducible hsp70 in the 510 kDa gel fraction containing the
      small hsps, but it could not be determined whether it was part of the multimer
      complex.

PMID- 9629673
TI  - Action of Al-ATP on the isolated working rat heart.
AB  - ATP is an important extracellular messenger in the coronary vasculature of the
      heart. To be effective its extracellular concentration must be tightly controlled
      and this is achieved via ectonucleotidases located in the luminal surface of the
      coronary endothelium. Al-ATP is a potent inhibitor of the hydrolysis of ATP and
      we speculated that Al-ATP released by cells into the blood would disrupt the
      signalling function of extracellular ATP. We tested this hypothesis by perfusing
      isolated working Wistar rat hearts with buffers containing either ATP or Al-ATP.
      The functional parameters measured were, coronary flow, heart rate and pulsatile
      power. A number of control perfusions including adenosine, ATP-gamma-S and Al
      were used to identify those effects which might be specific to ATP and Al-ATP. Al
      ATP did not appear to inhibit the function of the endothelial ectonucleotidases.
      Both ATP and Al-ATP produced a significant increase in coronary flow and this
      could be attributed to a coronary vasodilation. Interestingly, whilst the effect
      of ATP was reversible that of Al-ATP was not. ATP caused a reduction in heart
      rate which was potentiated by aluminium. The negatively chronotropic effect of Al
      ATP was mediated via a mechanism which was either distinct from or in addition to
      the similar response known to be caused by adenosine. We have demonstrated for
      the first time an influence of Al-ATP on heart function. Perhaps more pertinently
      we present the first evidence that Al-ATP may influence the function of ATP
      specific receptors.

PMID- 9629672
TI  - Metabolic evolution in alpha-amylases from Drosophila virilis and D. repleta, two
      species with different ecological niches.
AB  - alpha-Amylases from Drosophila virilis and D. repleta were partially purified by
      ion exchange chromatography. The two amylases share common characteristics for pH
      and cations effects, although with slight differences. D. virilis has optimal
      activity at pH 6.6 and D. repleta at pH 7.2. Calcium, sodium, and potassium
      cations activate amylolytic activity in both species but Ba2+ has an activation
      effect in D. repleta only. In contrast, there are major differences in thermal
      offbility and kinetics among amylases of the two species. D. virilis amylase is
      much more stable at high temperature and the optimal temperatures are very
      different between the two species, respectively, 45 degrees C and 30 degrees C
      for D. virilis and D. repleta. alpha-Amylase activity using different substrates
      is greater on starch than on glycogen in both species and still higher on amylose
      for D. virilis, the nonfungus feeder species. alpha-Amylase of D. repleta, the
      mycophagous species, has a better affinity to amylopectin and glycogen. Such
      differences in substrate specificity suggest adaptation to different resources in
      these species living in different habitats. Metabolic evolution seems to have
      occurred through a "tradeoff" between kinetic effectiveness and the nature of
      substrate, with a higher Vmax on amylose for D. virilis and a lower K(m) on
      glycogen for D. repleta.

PMID- 9629674
TI  - Specificity of an anti-aluminium monoclonal antibody toward free and protein
      bound aluminium.
AB  - Anti-aluminium monoclonal antibodies (mAbs) were prepared using aluminium
      chloride-bovine serum albumin complex (Al-BSA) as immunogen. Competitive enzyme
      linked immunosorbant assay (ELISA), using an Al-BSA coated immunoplate,
      demonstrated that mice immune sera showed stronger reactivity to AlCl3 than to
      BSA. Supernatants from hybridomas prepared from cloned anti-Al antibody-producing
      cells reacted in ELISA assays whether the metal was bound to proteins like
      calmodulin (CaM) and S100b protein or to immunogen BSA. Moreover, addition of
      citrate, a potent ligand for trivalent cations, resulted in a significant
      withdrawal in mAb recognition of aluminium which was previously bound to either
      CaM or S100b proteins. The anti-Al mAbs also reacted with aluminosilicate
      complexes formed from aluminium chloride and silicic acid. The results indicate
      that the monoclonal antibodies recognized aluminium alone, aluminium bound to
      silicate, or aluminium bound to a protein core and thus may be used as an
      immunologic tool for identifying aluminium in both in vitro and in vivo systems.

PMID- 9629675
TI  - Gastrointestinal absorption of aluminium and citrate in man.
AB  - Aluminium (Al) is an abundant terrestrial element, but toxic to tissues,
      including brain. The body is largely protected because systemic Al absorption is
      very low and in normal individuals almost all absorbed Al is excreted from the
      body. However gastrointestinal (Gl) absorption is enhanced by organic acids,
      including citrate. Aluminium and citrate Gl absorption was measured in three
      healthy males, aged 40-46. After overnight fast, subjects drank a 100 ml fruit
      drink containing 280 mg Al and 3.2 g citrate (104 and 167 mM, respectively). Al
      was measured in timed blood and urine samples by GFAAS and serum citrate by
      enzymatic assay. Blood Al peaked by an increase of 13 +/- 2.1 micrograms/l after
      87 +/- 19 min then fell slowly over 24 h. Plasma citrate peaked after 32 min,
      returning to baseline by 90 min. Al was excreted at a constant rate for the first
      24 h, 0.4% of the dose being excreted in urine by this time. It is unlikely that
      Al is absorbed as Al citrate because the blood citrate peak preceded the Al peak
      by 45-60 min.

PMID- 9629677
TI  - Kinetics of uptake and elimination of silicic acid by a human subject: a novel
      application of 32Si and accelerator mass spectrometry.
AB  - Silicon is possibly important in human physiology in protecting against the toxic
      effects of aluminium, but the kinetics of uptake and excretion of silicic acid,
      the bioavailable form, are not well characterised. We have used 32Si as a tracer
      in a human uptake experiment to determine a gastrointestinal uptake factor for
      silicic acid, and to elucidate the kinetics of renal elimination. Urine
      collections were made for extending intervals from 2 to 12 h over 2 days
      following ingestion by a single human subject of a neutral silicic acid solution
      containing tracer levels of 32Si (t1/2 approximately 150 y). Silicon was isolated
      as SiO2 and the 32Si content determined by accelerator mass spectrometry (AMS),
      using a gas-filled magnet technique to eliminate a prolific isobaric interference
      from 32S. Silicon uptake appears to have been essentially complete within 2 h of
      ingestion. Elimination occurred by two simultaneous first-order processes with
      half-lives of 2.7 and 11.3 h, representing around 90% and 10%, respectively, of
      the total output. The rapidly eliminated 32Si was probably retained in the
      extracellular fluid volume, whilst the slower component may represent
      intracellular uptake and release. Elimination of absorbed 32Si was essentially
      complete after 48 h and was equivalent to 36% of the ingested dose. This
      establishes only a lower limit for gastrointestinal absorption as, although there
      was no evidence for longer term retention of additional 32Si, the possibility
      could not be excluded by these results.

PMID- 9629676
TI  - Increased absorption of aluminium from a normal dietary intake in dementia.
AB  - Serum aluminium was significantly raised (p < 0.01) up to 2-3-fold, in patients
      with dementia including Alzheimers Disease (AD) 0.66 +/- 0.2 (mumol/l mean +/- 1
      s.d.) and patients on regular aluminium hydroxide therapy 0.54 +/- 0.17, compared
      with healthy volunteers 0.21 +/- 0.13, although not as high as in patients with
      end stage renal failure on regular dialysis 0.88 +/- 0.42. The urine outputs
      (mumol/l mean +/- 1 s.d.) of aluminium and silicon, respectively, were also
      significantly increased up to 5-fold in dementia 2.89 +/- 1.78 (n = 23) and 1587
      +/- 645 (n = 22) and patients on regular aluminium hydroxide therapy 5.03 +/-
      2.08 (n = 8) and 998 +/- 364 (n = 21) compared with healthy volunteers 0.95 +/-
      0.82 (n = 84) and 471 +/- 332 (n = 114). The increase in urine aluminium was thus
      associated with a similarly marked increase in the output of silicon. The
      increased absorption of aluminium in dementia patients is equivalent to the
      intestinal loading in Aludrox therapy. Also silicon appears to be important in
      the renal excretion of the absorbed aluminium. Whether this is a phenomenon
      related to the elderly or the process of dementia warrants further study.

PMID- 9629678
TI  - Aspects of the bioinorganic chemistry of silicon in conjunction with the
      biometals calcium, iron and aluminium.
AB  - Silicon, in its various forms (silicic acid (Si(OH)4) through to hydrated
      amorphous silica (SiOn(OH)4-2n, n = 2-4) is important in geological and
      biological processes. Silicon is considered to be an 'essential' element for some
      plants and higher animals and when present as silica imparts structural,
      defensive and photosynthetic advantages to many plants. For the majority of
      essential elements specific molecular binding sites have been identified, but
      this is not the case for silicon. This has lead to the proposal that silicon may
      not act directly on biological systems but may exert its influence via
      interactions with biometals. Metals for which this may be a viable option include
      aluminium, iron and calcium, all of which can be found co-located with silicon in
      both minerals and living organisms. This article briefly reviews the pertinent
      solution and solid state chemistry of silicon in relation to aluminium, iron and
      calcium. Examples where silicon and an additional metal are found in solid state
      phases are described. The biological systems where these deposits are found are
      extremely complex and preliminary results from a model system designed to study
      silicon-biometal interactions are described.

PMID- 9629679
TI  - Environmental degradation pathways for the breakdown of polydimethylsiloxanes.
AB  - The following paper describes how polydimethylsiloxane (PDMS) polymers, which are
      present in a wide range of consumer products may undergo environmental
      degradation in the environment. The mechanism involves a biological degradation
      by bacteria and/or fungi, which takes place after an initial abiotic reaction
      initiates depolymerisation. The available information indicates that ultimately
      PDMS is converted to its inorganic constituents, namely carbon dioxide and
      silicic acid.

PMID- 9629680
TI  - [Coronary arteriography with a very low profile catheter: efficacy and safety of
      the procedure and of the 60 minute hospital discharge].
AB  - PURPOSE: To evaluate the feasibility, efficacy and safety of the use of 4F
      Judkins catheters for coronary angiography. METHODS: From August/95 to
      January/96, 70 patients with suspected coronary artery disease underwent coronary
      cineangiography by the Judkins technique, with 4F catheters. Following puncture
      of the right femoral artery, 4F sheaths were introduced. At the end of the
      procedure, the sheath was removed and manual compression was applied for 15 min.
      Patients were oriented to walk under specialized supervision, 60 min after the
      procedure, and discharged after 4h. RESULTS: Thirty nine (56%) patients were
      male, the age ranged from 31 to 83 (mean 57) years and weight from 43 to 101
      (mean 69) kg. Optimal quality images were obtained in 62 patients (88%). It was
      necessary to use larger caliber catheters (6 and 8F) in 8 patients, due to
      femoral tortuosity or inadequate opacification of coronary arteries. There were
      no vascular complications nor major bleedings. In only 2 cases (3%) there was a
      minor bleeding, treated by new local compression. Sixty (85%) patients walked
      after 60 +/- 5 min and were discharged after 4h. CONCLUSION: The use of 4F
      catheters for coronary angiography by femoral approach allowed early deambulation
      with no major bleeding. Image quality was good, with little contrast used and
      short hospital stay. This technique may lead to a simpler less traumatic and less
      invasive coronary angiography.

PMID- 9629681
TI  - [Treatment for overdose of oral anticoagulants].
AB  - PURPOSE: To evaluate the response of 73 patients with antivitamin K (AVK)
      overdose to 3 different therapeutic regimens. METHODS: Seventy three patients
      were evaluated in 94 occasions: group A (N = 32), consisted of drug withdrawal
      for 2 days followed by reduced dosage; group B (N = 37), drug withdrawal and
      reassessment within 4 days; group C (N = 25), oral administration of vitamin K.
      Therapeutic range was set between INR-values of 2 and 4. RESULTS: Reversal
      regimens did not result in differences among 61 patients who had initial INR < 8
      (chi 2 = 2.352, p = 0.671). There were more patients bellow therapeutic range in
      group C (N = 14) than group B (N = 19) (chi 2 = 9.998, p = 0.007). After
      intervention, 7 patients in group B still had INR > 4, but 5 of them were bellow
      4.5, without increased bleeding risk. There were 10 patients in group C bellow
      therapeutic range, 6 of them with INR < 1.6, with risk of thromboembolism.
      Thirteen patients bled, but none required transfusion. CONCLUSION: Reversal of
      excessive oral anticoagulation can be safely performed by initial withdrawal of
      the drug, followed by lower doses. Vitamin K administration may lead to INR
      bellow the therapeutic range. This should be reserved for patients with high INR
      or in the presence of bleeding.

PMID- 9629682
TI  - [Cardiorespiratory response during exercise in heart transplant recipients.
      Comparative ergoespirometric analysis with normal health subjects].
AB  - PURPOSE: To evaluate the cardiorespiratory response of heart transplant (HT)
      recipients. METHODS: Nine HT recipients (GI) underwent ergospirometric tests and
      were compared to 9 apparently healthy, sedentary subjects with similar sex, age,
      weight and height (GII). All were male patients aging 48 +/- 12 years, in
      functional class I (NYHA) an average of 23 +/- 21 months after HT. They were
      receiving cyclosporin, azathioprine, prednisone, dipyridamole and
      antihypertensive drugs. The tests were symptom-limited and they were interrupted
      due to exhaustion. RESULTS: During peak exercise, GI had a significantly lower
      physical performance related to lower VO2, VE, VEO2, HR, endurance time and work
      load. At the anaerobic threshold, VO2, endurance time and work load levels were
      also significantly lower in GI. The physical performance was similar between the
      groups in the 40W load. CONCLUSION: The cardiorespiratory performance in GI was
      significantly lower at peak exercise and similar to GII in the 40W load, showing
      the HT benefits cardiac patients during usual activities.

PMID- 9629683
TI  - [Morphological changes in muscular arterial walls in hypertensive patients].
AB  - PURPOSE: To identify structural lesions in the wall of uterine arteries in
      hypertensive women. METHODS: Twenty six patients who underwent an elective
      hysterectomy were selected and separated in two groups. Group 1 was formed by
      women with normal blood pressure and group 2 consisted of hypertensive patients
      without regular treatment. Two segments of the uterine artery were obtained from
      every patient shortly after surgery. The fragments were fixed, sliced and
      stained. The morphological study was carried out using optical microscopy.
      RESULTS: Age was similar in both groups with means of 46.8 +/- 7.6 and 46.7 +/-
      6.4 years-old in groups 1 and 2, respectively. The average maximal systolic and
      diastolic blood pressure during hospital admission were 130.0 +/- 3.4 and 83.8 +/
      6.5 mmHg in the control group and 163.8 +/- 4.3 and 105.8 +/- 9.9 mmHg in the
      hypertensive group (p < 0.0001). Hypertensive women had larger intimal thickness
      (p < 0.05). Elastic fibers were also more numerous and homogeneous in group 2.
      Cellular hypertrophy was more common in this group than in control patients
      (53.8% vs 23.1%). CONCLUSION: Hypertension seems to accelerate the age-related
      increase in intima thickness. Hypertensive women have more numerous and
      homogeneous elastic fibers in the wall of the uterine artery. These findings
      indicate that hypertension may determine structural changes similar to vascular
      aging.

PMID- 9629684
TI  - [Treatment of membranous subaortic stenosis with balloon dilatation].
AB  - PURPOSE: This study sought to evaluate the immediate and follow-up results of
      percutaneous balloon dilatation for the treatment of membranous subaortic
      stenoses. METHODS: Fourteen patients with mean age 11.4 +/- 5.2 years, were
      submitted to the procedure. They were selected when the echocardiogram showed a
      thin subaortic membrane that was far from the aortic valve, no fibro-muscular
      obstruction and only mild or moderate aortic regurgitation. After measuring the
      pressure gradient and analysis of the angiographic features, the balloon
      dilatation was made by applying a fast manual inflation until the balloon waist
      disappeared. The balloon diameter was the same as that of the outflow tract of
      left ventricle, immediately bellow the aortic valve. Pressure measurement, left
      ventriculogram and aortogram were repeated. Doppler echocardiogram was repeated
      in the following day, after 3 months and every 6 months thereafter. RESULTS: All
      17 procedures were successful. The mean gradient was 76.1 +/- 21.2 mmHg before
      and 29.8 +/- 8.8 mmHg after dilatation (p < 0.01). There was no increase in
      aortic regurgitation or death after the procedure or during the follow-up. Twelve
      patients were discharged 24h after the procedure. Surgical treatment for femoral
      artery thrombosis was performed in 2 patients. In the follow-up of 33.3 +/- 23.6
      months, 4 patients developed restenosis and 3 of them were submitted to
      successful redilatation. CONCLUSION: We conclude that in selected cases, the
      procedure is safe and effective, and restenosis may be treated by percutaneous
      balloon redilatation.

PMID- 9629685
TI  - [Hemostatic changes in children treated with heart surgery with cardiopulmonary
      bypass].
AB  - PURPOSE: We evaluated hemostasic changes in children undergoing open heart
      surgery with cardiopulmonary bypass (CPB). METHODS: We studied 17 children
      before, during surgery, in the immediate, first and between the 4th and 7th
      postoperative days, measuring hematocrit, prothrombin time, activated partial
      thromboplastin time, fibrinogen, platelet count, factor V and euglobulin lysis
      time. Children were divided in those with and without excessive bleeding in the
      postoperative period. RESULTS: We observed significant prolongation of
      prothrombin time and activated partial thromboplastin time, reduction of
      fibrinogen and factor V, and shortening of euglobulin lysis time. Six (35%)
      children bled excessively. Platelet count reduction was greater in the intra
      operative period in these cases and the duration of CPB was longer in this group.
      CONCLUSION: Changes in hemostasis during open heart surgery are due to
      coagulation cascade disorders as well as fibrinolysis. The incidence of excessive
      bleeding is higher in the pediatric group. Prolonged CPB time and greater
      reduction in platelet count differentiated both groups.

PMID- 9629686
TI  - [Multicenter study of intracoronary stent implantation in Rio de Janeiro].
AB  - PURPOSE: To evaluate retrospectively stent implantation (SI) in patients with
      coronary artery disease (CAD) performed in 7 hospitals in Rio de Janeiro.
      METHODS: From June/94 to December/96 2,220 procedures were performed among which
      we analyzed 783 SI in 660 (29.7%) patients using coronary angiography without
      digital subtraction. Several types of stents were used: Palmaz-Schatz (40.9%),
      Gianturco-Roubin (29.1%) e NIR (22.0%). Indications for SI: 1--de novo lesion
      (67.9%); 2) restenotic lesion (16.0%); 3) sub-optimal results after PTCA (8.2%);
      4) abrupt or threatened closure after PTCA (4.9%); 5) chronic occlusion (3.0%).
      All stents were implanted using high pressure balloon inflation without
      intracoronary ultrasound guidance. Sub-acute stent thrombosis prevention, in the
      majority of patients (87.8%) was done with ticlopidine and aspirin. RESULTS:
      Early outcome: a) the success rate of SI in 770 lesions was 98.0% in 646 (97.9%)
      patients; b) the clinical success rate in 634 patients was 96.0%; c) the major
      complications were acute myocardial infarction (1.1%); coronary artery bypass
      graft (1.4%) and death (0.8%); d) vascular complications with surgical correction
      and/or bleeding occurred in 3.0%. Late outcome: a) the clinical follow-up of 399
      (60.4%) and the coronary angiographies of 121 patients (30.3%) showed in-stent
      lesion in 79 (19.8%); b) other event rates: myocardial infarction (1.5%);
      coronary bypass (2.3%); death: 1.0% and other PTCA or similar procedure (12.5%).
      CONCLUSION: This multicentric study showed that SI for CAD can be performed with
      safety, high early success rate, few complications and low rate of cardiac events
      during the late follow-up.

PMID- 9629687
TI  - [Analysis of atrial fibrillation recurrence during therapy with sotalol or
      quinidine. Researchers of +SOCESP].
AB  - PURPOSE: To analyze the recurrences of atrial fibrillation in patients treated
      with sotalol or quinidine. METHODS: After conversion to sinus rhythm, 121
      patients with paroxysmal atrial fibrillation were randomized to sotalol (58
      patients) or quinidine (63 patients) and followed-up during 6 months. Symptoms
      and ventricular rates on the 12 lead electrocardiogram of the arrhythmic events
      were compared between the two groups. Clinical and echocardiographic
      characteristics were analyzed as predictors of atrial fibrillation recurrence.
      RESULTS: Seventeen (14%) patients relapsed into atrial fibrillation; 7 (12%) were
      treated with sotalol and 10 (16%) with quinidine. Recurrence occurred later in
      the sotalol group (median 69 days) in comparison with the quinidine group (median
      10 days) (p = 0.04). Symptoms were present in 14 (82%) patients during the
      initial crisis and in 10 (47%) during recurrence. Recurrence was less symptomatic
      during antiarrhythmic therapy (p < 0.04), with no statistical differences between
      the two groups. Only patients treated with sotalol had ventricular rates during
      the recurrences lower than during initial crisis (p < 0.02). All variables failed
      to predict recurrence of atrial fibrillation. CONCLUSIONS: It was not possible
      demonstrate differences between sotalol and quinidine for the prevention of
      atrial fibrillation. Recurrence was less symptomatic during antiarrhythmic
      therapy. Patients treated with sotalol relapsed to atrial fibrillation later and
      had ventricular rates during recurrences significantly lower than during the
      initial crisis.

PMID- 9629688
TI  - [High output heart failure due to coronary fistula].
AB  - A 45 year-old woman complaining of heart failure symptoms (New York Heart
      Association--class III) and a non typical thoracic pain was submitted to a
      transthoracic echocardiogram which showed a very dilated coronary artery and a
      fistula to the right atrium. The angiograms confirmed the same findings. She
      underwent open heart surgery which confirmed the diagnosis. Fistula ligation was
      then undertaken. She remains symptom-free three years after the operation.

PMID- 9629689
TI  - [Stenting for iatrogenic coronary dissection treatment].
AB  - Catheter-induced coronary dissection is rare but has a significant mortality and
      morbidity. The ideal management of acute coronary occlusion, whatever the cause,
      is the prompt restoration of the vessel patency to limit the extent and duration
      of ischemia. In the setting of dissection during angiography the usual approach
      to myocardial salvage has been emergency aortocoronary bypass surgery preceded by
      insertion of an intra-aortic balloon. The main disadvantages of this approach is
      the delay in performing emergency surgery, mainly in centers without surgical
      back-up on site. The authors present a case of an elderly woman with left
      circumflex artery dissection caused by the catheter during coronary angiography.
      This problem was successfully managed using an intracoronary stent. This
      technique has potential advantages in terms of the speed of reperfusion and
      availability in centers performing diagnostic angiography without surgical back
      up on site.

PMID- 9629690
TI  - [Therapeutics for the chronic form of Chagas' disease. Is the etiological
      treatment effective?].

PMID- 9629691
TI  - [Therapeutics of the chronic form of Chagas' disease. Specific treatment of
      Trypanosoma cruzi infection].

PMID- 9629692
TI  - [Myocardial apoptosis. A new mechanism of cellular death].

PMID- 9629693
TI  - [Tetralogy of Fallot in the newborn: surgical correction or palliative
      technique].

PMID- 9629694
TI  - [Surgery for pulmonary emphysema: waiting for evidence].

PMID- 9629695
TI  - [Psychological aspects and essential arterial hypertension].
AB  - In addition to organic and hereditary factors, psychological variations among
      individuals are also known to play an important role in the etiology of essential
      arterial hypertension. OBJECTIVE: To investigate in detail the psychological
      processes possibly involved in the etiology of essential arterial hypertension.
      METHODS: A group of 20 subjects, all of whom where diagnosed as suffering from
      essential arterial hypertension, was studied using psychological interviews and
      the Rorschach Test. The results obtained were compared with those gathered from
      normal (non-hypertensive) individuals represented by the Rorschach Test for the
      Brazilian population. RESULTS: In terms of personality structure, the
      hypertensive group presented signs of subjective and immature mechanics which
      prevailed over more mature and adult traits. These characteristics lead the
      patients to emotional withdrawal as a defense inadequate affectivity. CONCLUSION:
      The blocking of emotional expression, as well as simultaneous anxiety, may affect
      the autonomic nervous system and lead to periodic transitory hypertensive crises
      which, with time assume a permanent nature.

PMID- 9629696
TI  - [Evolution of beta-hCG titers after systemic treatment of unruptured ectopic
      pregnancy].
AB  - OBJECTIVE: The follow-up of this treatment is done by monitorization of beta-hCG
      titers. The objective of this study is to evaluate the beta-hCG titers after
      treatment with MTX. METHODS: Twenty four women were included in the study. The
      inclusion criteria were: ectopic pregnancy < or = 4.5 cm, beta-hCG < or = 15.000
      mIU/mL, desire of future pregnancy and a written permission to participate in the
      study. All patients were treated with a single dose of methotrexate (50 mg/m2
      IM). Patients were monitored with beta-hCG titers on days 1, 4 and 7 after the
      MTX injection, and then weekly until the beta-hCG was less than 25 mIU/mL.
      RESULTS: The variation of the titers of beta-hCG between day 1 and day 4 after
      MTX was the following: increase 50.0%, decrease 33.3% and in levels less than 25
      mUI/mL in 16.7% of the cases. The variation of the titers of beta-hCG between day
      4 and day 7 after MTX was the following: decline > or = 15% in 85.7% of the
      cases, and decline < 15% in 14.3%. There was the necessity of a second dose of
      MTX in only two cases (8.4%), since the levels of beta-hCG declined less than
      15%, in this period. CONCLUSION: The titers of beta-hCG increase in 50.0% of the
      cases, so it is a frequent event. The understanding of this evolution of beta-hCG
      titers avoids surgery in the first week of the treatment.

PMID- 9629697
TI  - [Laboratory diagnosis of auto-immune hemolytic anemia: characteristics of the
      manual direct test of Polybrene].
AB  - The direct manual Polybrene test (DPT) and the direct antiglobulin tests (DAT)
      were employed to detect antibody sensitizing red blood cell (RCB) in patients
      with clinical and laboratorial findings of autoimmune hemolytic anemia (AIHA).
      PURPOSE: To compare the sensitivity and specificity of DPT and DAT in the
      diagnosis of AIHA. METHODS: Eighteen consecutive patients with diagnosis of AIHA
      were evaluated. The control group consisted of 20 normal volunteers blood donors
      and 20 patients with sickle cell anemia. All patients and controls were submitted
      to DPT and DAT. All DAT positive samples were further tested using monospecific
      reagents (anti-IgG heavy chain and anti-C3d). Positive samples for either DPT or
      DAT were evaluated by eluate technique using. The dichloromethane (DCM). RESULTS:
      The DAT was positive in 14 patients and negative in 4 subjects, while the DPT was
      positive in 17 patients and negative in 1 individual who had a positive DAT owing
      to complement (C3d). All positive eluates performed with DCM showed RBC
      autoantibodies with presumed "anti-Rh" specificity. The sensitivity rate of the
      DPT (94%) was significantly (p < 0.05) higher than the sensitivity rate of DAT
      (78%) to determine whether IgG was bound in vivo, but no difference was found
      regarding the specificity of the two tests. CONCLUSION: 1) The DPT is more
      sensitive than the DAT in detecting IgG autoantibody on the RBCs of patients with
      AIHA; 2) because of its simplicity and rapidity, the DPT is a useful additional
      screening test for the investigation of Coombs-negative AIHA.

PMID- 9629698
TI  - [The student, the physician, and the teacher of medicine facing death and
      terminal patients].
AB  - OBJECTIVE: The aim of this investigation was to study the feelings and attitudes
      of medical students, medical doctors and teachers of medicine facing death and
      terminal patients. METHOD: An inquiry about death and terminal patient was
      applied to 81 pre-clinical students, 139 clinical students, 52 medical doctors
      and 54 teachers of the Faculty of Health Sciences. RESULTS: 303 responders showed
      interest in this subject (93%); 179 had problems in dealing with it (55%). Only
      136 searched for information (41.7%) and 116 have difficulty in finding it
      (85.1%). Non-especialized sources of information were the most used ones (61.1%).
      Twenty medical doctors (38%) and 13 teachers (24%) discussed the subject more
      often with patients, 47 pre-clinical students (58%) did it with friends and 40
      with relatives (49.4%); 36 teachers did it with health professionals (66.6%). 263
      responders rarely think about their own death (80.7%), and 38 do it constantly
      (11.6%); 157 are afraid of thinking about their own death (52.2%). Eleven pre
      clinical students (13.8%), ten clinical students (7.2%) and 4 medical doctors
      (7.4%) never thought of their own death. Before entering medical school, 136
      responders had some kind of contact with corpses (41.8%). The interest about
      death did not change, after dealing with corpses in anatomy classes, to 321
      responders (98.5%), the same happening with 236 individuals (96.3%) after
      necroscopy. During the clinical year 111 students (79.9%) worked with terminal
      patients. CONCLUSIONS: The authors suggest that formal education about death and
      terminal patient in medical schools, starting early in the medical course, as
      well as permanent attention to the theme by professionals, could modify the
      attitudes of students and medical doctors toward a better way in dealing with
      this subject.

PMID- 9629699
TI  - [Stress nature and magnitude during medical residency training].
AB  - The stressful nature of Residency training has been largely discussed in the
      literature. The aim of this paper is to present some data about the stress of
      training and its effects on residents and on the quality of patient's care. The
      magnitude of stress results from the interaction of three categories of stresses:
      professional, situational and personal. The main behavioral disturbances and
      professional dysfunctions are described and the importance of these data for
      planning, organization and evaluation of Residency programs is emphasized.

PMID- 9629700
TI  - [The client-doctor interaction].
AB  - The author re-labels the traditional concept of "patient-doctor relationship" as
      "client-doctor interaction", which is reviewed as part of a larger group of
      phenomena called "health professional-client interactions". The main emotional
      reactions in this interaction are discussed, as well as the context in which
      happen. Some procedures in order to establish a good work alliance with the
      client, and make some remarks about the desirable personal attributes of the
      doctor are suggest.

PMID- 9629701
TI  - [Extraskeletal primary osteosarcoma of the frontal region].
AB  - BACKGROUND: Extraskeletal osteosarcoma (ESOS) in the head as a primary site has
      seldom been reported and none in the frontal region. METHODS: A 78-year-old
      Italian man presented with one month history of a frontal soft tissue mass. A CT
      scan showed a mass of uneven density occupying the subcutaneous soft tissue and
      involving fascial planes. No primary bone tumor was found. The entire mass was
      excised. The mass was solid measuring 0.8 x 0.6 x 0.5 cm. Extraskeletal
      osteoblastic osteosarcoma was diagnosed by light microscopy. The tumor recurred
      four months after the diagnosis. The tumor was again ressected. The patient was
      also submitted to low penetration radiation therapy. Nine months after the first
      biopsy the patient had symptoms due to infiltration to the base of the cranium.
      He died 10 months after the first biopsy. CONCLUSIONS: The first case with ESOS
      of the frontal region without a pre-existing condition or a history of
      irradiation is described.

PMID- 9629703
TI  - [Neurocutaneous melanosis. Case report of a malignant melanoma of the central
      nervous system].
AB  - The neurocutaneous melanosis is a rare syndrome in which the congenital
      melanocytic nevi and excessive melanosis are the main features. The syndrome
      seems to be a morphogenesis error of the embryonic neuroectoderm. A clinical case
      with necroscopy in a 19 year-old man who had developed malign melanoma in his
      central nervous system is reported.

PMID- 9629702
TI  - Anatomical and clinical aspects of the blood supply of the sinoatrial node.
AB  - BACKGROUND: The recent study of the variations of the origin of the sinoatrial
      node and on the "arterial network of the perinodal sinusal area" in normal hearts
      points out the importance of this network. PURPOSE: Report on a case of patient
      with syncope of ischemic etiology. CONCLUSION: In this patient the arterial
      network did not protect the node from the ischemia caused by the obstruction of
      the artery of the sinoatrial node.

PMID- 9629704
TI  - [Toxic epidermal necrolysis after the use of intermediate dose of cytosine
      arabinoside].
AB  - Toxic epidermal necrolysis is a drug-induced dermatologic disease related to
      Lyell syndrome, erythema multiforme and Stevens-Johnson syndrome. PURPOSE: To
      report a fatal case of toxic epidermal necrolysis owing to intermediate dose of
      cytarabine. CASE REPORT: A 16 year-old female patient with acute lymphocytic
      leukemia (LLA-L1) treated with the Protocol of the Brazilian Group for Treatment
      of Leukemia of Childwood (GBTLI-85-AR). On the second day after the
      administration of intermediate dose of cytarabine (1.5 g/m2 i.v. every 12 hours
      for 3 days), she presented bullous lesions in the left buttock that disseminated
      envolving to necrosis, sepsis, and death on the 13th day. CONCLUSION: Cytarabine
      is frequently associated with dermatologic toxicity but, until now, there is no
      other case of toxic epidermal necrolysis described.

PMID- 9629705
TI  - [Sedation and analgesia for children].

PMID- 9629706
TI  - [Evaluation of occupational deafness].

PMID- 9629707
TI  - [Systemic effects and withdrawal syndrome in chronic users of corticosteroids].

PMID- 9629708
TI  - [Inequality and public health].

PMID- 9629709
TI  - [Productivity of a breeding place of Aedes albopictus in an urban environment].
AB  - INTRODUCTION: Aedes albopictus has been found at Cananeia city in the
      Southeastern State of S. Paulo, Brazil. A study was carried out to evaluate the
      productivity of its breeding place. MATERIAL AND METHOD: A container classified
      as large and permanent was chosen. Water had accumulated at the bottom and was
      rich in organic matter, mainly of vegetal origin. From November 1996 until May
      1997, fortnightly observations were performed, sampling immature stages found in
      a seventh part of the container's total water volume (nearly 70 litres). Pupae
      were collected, identified and sexed. The productivity of the breeding place was
      estimated using Focks et al's. (1981) formula adapted for a single large
      container. At the same time adults were caught by using human bait and the
      aspiration of resting places. The first catch was performed at six meters from
      the breeding place studied. Williams' mean was calculated for the human bait and
      mean hourly density for the aspiration results of the resting places (Subbarao et
      al., 1988). RESULTS: Immature stages of Ae. albopictus represented 44.9% of the
      total collected through fifteen fortnightly regular samplings (November 1996 to
      May 1997). The pupae mean was 31.13 and so the emergence index was 2.1.
      Multiplied by seven the result was 14.7 as the estimated mean number of females
      per day produced in that container. Adult females caught on human bait gave a
      general Williams' mean of 30.7, while the mean hour by density was 9.2. According
      to the accumulated calculated adult number, 22.8 females per day were available
      to seek human bait, under the conditions of the observations performed.
      DISCUSSION: Counting pupae is an efficient method of estimating the productivity
      of the breeding place of Ae. albopictus. The richness of the organic matter in
      the water in the container made it quite inappropriate to establish comparisons
      with water reservoirs for domestic use. Nevertheless, a lack of or deficient
      maintenance approximate these containers to the one here studied. So cleaning is
      an important factor and it must be emphasized as necessary to prevent the
      installation of mosquito breeding. Though it is a distinct species it is
      reasonable to expect that the application of these study methods to Ae. aegypti
      would be useful in the attempt being made to eradicate this latter species from
      our country.

PMID- 9629710
TI  - [Proxy informant reliability and bias in epidemiological research: analysis of a
      screening questionnaire for mental disorders].
AB  - OBJECTIVES: To evaluate the reliability, magnitude and direction of the resulting
      bias in the application of a screening instrument for mental disorders by
      considering proxy informants in comparison to primary informants. METHODS: Data
      are taken from a general morbidity community-based survey carried out in 520
      randomly selected households of an industrial area of the Metropolitan Region of
      Salvador, the capital of Bahia state, Brazil. During the pilot phase, the first
      70 families of the total sample were asked to participate in the evaluation of
      research instruments. The Questionnaire of Adult Psychiatric Morbidity, QAPM,
      consists of 44 questions about psychiatric symptoms widely used in Brazil. The
      husbands and wives of the selected families answered QAPM questions regarding
      themselves and their respective partners. One family refused to participate. The
      Kappa index was estimated for each QAPM question. To assess the magnitude and
      direction of bias, the proportional variation of prevalence was estimated from
      proxy and primary respondents. Each informant was analyzed as a primary informant
      when answering about his/her own symptoms and as a proxy informant when answering
      those about his/her partner. RESULTS: Proxy informants as compared to primary
      informants show weak reliability, as measured by the Kappa Index, particularly
      when husbands reported on their wives' symptoms. An overall underestimation of
      prevalence estimates was found, which reveals the potential negative bias with
      the use of proxy informants for psychological symptoms. No bias was found for
      only two questions (lack of appetite and globus hystericus) when women were taken
      as proxy informants for their husbands. In addition, departures of proxy
      informants from primary informant-based estimates were greater among men than to
      women. CONCLUSIONS: Proxy informants underestimate the occurrence of
      psychological symptoms in this community-based study. When the feasibility of a
      research project, based on the QAPM depends on the use of proxies, wives may be
      recommended as better informants than their husbands.

PMID- 9629711
TI  - [Women's opinion on abortion legalization in a middle size county in southern
      Brazil].
AB  - INTRODUCTION: Induced abortion is the main cause of maternal death in Brazil.
      Question of its legalization has been the subject of frequent discussion.
      MATERIAL AND METHOD: In order to assess the influence of the variables affecting
      the opinion of women of reproductive age, a population-based systematic sample in
      the county of Rio Grande (Southern Brazil) was examined. RESULTS: Of a total of
      1,456 interviews 30% endorsed the legalization, whatever the circumstances; this
      percentage was directly associated with age, schooling, family income and
      previous induced abortion (p < 0.01). Adjusted analysis using logistic regression
      showed a significant effect of schooling and previous induced abortion on
      favourable opinion. CONCLUSION: Schooling and previous induced abortion were the
      main determinants of women's favorable opinions regarding abortion legalization.

PMID- 9629713
TI  - [Characterization of liveborn infants at hospitals in the first year of
      implementation of the Information Subsystem on Liveborn infants in a municipality
      of Minas Gerais, Brazil, 1996].
AB  - INTRODUCTION: The liveborn children were classified by birth weight, maternal
      age, maternal education level and type of delivery in the light of the importance
      of discovering the conditions of birth for the planning of mother-child actions.
      METHODOLOGY: The population studied consisted of 2,315 liveborn children from the
      municipality of Passos (MG), 2,311 of whom were born in hospitals and 4 at home,
      although these latter were immediately taken to hospital. The data refer to the
      set of children born alive in the municipality from April 12, 1995 to April 30,
      1996. Data collection was facilitated by the implantation of the Subsystem of
      Information about Liveborn Children (SINASC) during that period. The instrument
      used for data collection was the Declaration of Liveborn Children, an official
      document of SINASC. The data were fed into a computer and the variables of
      interest for the present study were surveyed. RESULTS: The data showed that: the
      incidence of low birth weight was 10%, 31.1% of the mothers were between 20 and
      24 years old and 19.5% were younger than 20. With respect to educational level,
      68.6% of the mothers had received incomplete primary schooling and 5.7% had
      higher education. The proportion of cesarean sections was 59.1% and the
      proportion of spontaneous delivery 40.9%.

PMID- 9629712
TI  - [Rooming-in and cesarean section in maternity hospitals in the State of Rio de
      Janeiro, Brazil].
AB  - OBJECTIVE: To disclose the existence of rooming-in (RI) in public and government
      contracted private hospitals that offer obstetric beds, in the State of Rio de
      Janeiro, Brazil, and to examine whether there is any association between RI and
      another quality care indicator which influences breastfeeding, namely the rate of
      cesarean section operations performed in these hospitals. METHODS: A survey was
      made of the existence of RI through a questionnaire sent to the Municipal Health
      Offices, the information collected being confirmed by telephone with each
      maternity hospital. The C-section rate data was obtained from the Rio de Janeiro
      State Health Office and divided into 2 groups: "below 40%" and "40% and above".
      The prevalence ratio was applied to the measurement of the association between
      the variables. RESULTS: A rooming-in rate of 65.2% was found for the State as a
      whole, with regional variations: a better situation in the capital (84.8%), an
      intermediate one in the interior (69.9%), and a worse one in the metropolitan
      belt (44.2%). The public maternity hospitals revealed a higher rate (89.7%) than
      that of the government contracted private hospitals (53.3%). A direct relation
      between the practice of RI and low C-section rates was found in the hospitals.
      However, this association did not present the same weight in all regions of the
      State. The lowest proportion of hospitals adopting RI was verified in the
      metropolitan belt, whereas the highest relative number of hospitals with high C
      section rates was observed in the interior. CONCLUSION: It is concluded that to
      reverse the observed status, government authorities must fulfil their gerencial
      role within their own health system, as well as in the government contracted
      private hospitals.

PMID- 9629714
TI  - [Oral hygiene habits among Brazilian adults in an urban area of southern Brazil].
AB  - AIMS: This study sought to analyse the oral hygiene habits (toothbrushing
      frequency, use of toothpick and dental floss), of a group of Brazilian adults, in
      relation to socio-demographic variables. The level of dental plaque and number of
      teeth with gums bleeding after probing were also investigated. METHODOLOGY: The
      sample was composed of 234 women and 237 men, from two socioeconomic status. The
      age range was from 24 to 44 years. Data was collected through structured
      interviews and clinical examinations. RESULTS: Daily toothbrushing was frequent.
      The median and mode were three, and it was associated with sex and socio-economic
      status. The majority of the sample population (67.5%), reported using dental
      floss and its use was associated with sex and socio-economic status. The use of
      toothpicks was frequent: 54.6% of the study group used them, and their use was
      also associated with sex, age and social class. The majority of the sample
      population had a moderate level of dental plaque (62.6%). The level of dental
      plaque was associated with social class. A quarter of the subjects did not have
      teeth with gums bleeding after probing. Bleeding gums were associated with age
      and social class. CONCLUSION: Oral hygiene habits were considered good for most
      of the participants of the study. However, improvements, are necessary among men
      and members of low social class.

PMID- 9629715
TI  - [Prevalence of dental caries in 12-year-old children in localities of the State
      of Sao Paulo, Brazil, in 1990-1995].
AB  - INTRODUCTION: Dental caries is the most prevalent disease of the oral cavity,
      leading to serious economic and social consequences. Studies on the prevalence of
      dental caries should be undertaken periodically for the adequate planning of oral
      health services and action. This research project sought to discover the
      prevalence of dental caries in the counties of S. Paulo State, Brazil, measured
      by means of the DMF-T rate on the 12 year-old bracket from 1990-1995. MATERIAL
      AND METHOD: Data originally produced by Municipal Health Departments, collected
      by means of an instrument devised for this purpose, sent to 625 counties in the
      state, were used. The counties concerned were grouped according to their size and
      geographical region. RESULTS: The total of 625 counties of S. Paulo State, 237
      (37.9%) provided the information required, and 125 (20.0%) had data on DMF-T
      corresponding to about 5,000 12 year-old children available examined. The study
      revealed that the prevalence of dental caries is low in only 4.0% of the
      counties, and is high or very high in approximately 80% of them. The DMF-T index
      values varied from 1.3 to 13.6, and the estimated average for all the counties
      was 4.8. Further, it was discovered that "large" counties recorded 54.6% of their
      population classified in the categories of low or moderate prevalence of caries;
      while in "small" counties 87.8% of the population corresponded to the high or
      very high caries prevalence range. CONCLUSIONS: This research project has shown
      that the country services for oral health in S. Paulo State have made little use
      of the basic resources that epidemiology can provide. This indicates the need for
      an appropriate professional background for oral health in epidemiology,
      especially for those who fulfil duties in the coordination of the services.

PMID- 9629716
TI  - [Service delivery and quality of hospital care in the State of Rio de Janeiro,
      Brazil--1992 to 1995].
AB  - INTRODUCTION: Recent trends in hospital care in the State of Rio de Janeiro,
      Brazil, are analysed. The data are taken from the Unified Health Care System
      (SUS) and cover monthly observations between January 1992 and October 1995 for
      the public, teaching and private hospital subsectors. METHODOLOGY: The data
      entries are based on hospital declarations on the AIH form, processed by the
      National Inpatient Information System (SIH-SUS). When comparing the three
      subsectors, production of services and outcome were examined particularly
      closely. Comparisons are made using structural models for time series based on
      the break-down of a time series into components of interest, such as trend,
      seasonal variation and irregularity. RESULTS: The analysis shows a significant
      downward trend in the frequency of hospital admissions in the State of Rio de
      Janeiro, probably reflecting the deliberate withdraw of financial investments in
      this sector, which began in 1993. This reduction was selective with regard to age
      group distribution--being greater in the adult and elderly groups. The analysis
      has also shown that the teaching sector has steadily raised its admissions. The
      quality of care was analysed through the sentinel event approach. For the State
      of Rio de Janeiro as a whole, the occurrence of avoidable deaths during the
      hospital admission process shows a weak overall tendency to decline as detected
      by the reduction of this kind of death in the private sub-sector. In public and
      teaching hospitals the frequency of avoidable deaths has remained stable. The
      frequency of maternal deaths has remained high and stable, while the number of
      caesarean sections shows a significant increase, despite the high figures
      observed at the beginning of the period. CONCLUSIONS: The results of this study
      indicate an overall decline in the quality of health care offered by the SUS
      within the Rio de Janeiro State. Regardless of the existing limitations in SIH
      SUS, this study has shown this to be a useful instrument for monitoring hospital
      care services.

PMID- 9629717
TI  - [Reference values for carboxyhemoglobin].
AB  - INTRODUCTION: The reference values (RV) of biological indicators are used in the
      interpretation of the results of such indicators in individuals occupationally
      exposed to chemical agents. The Brazilian Group for the Establishment of
      Reference Values has worked on these definitions for the purpose of establishing
      RVs for several bioindicators in various regions of the country. In the present
      study, the RV for carboxyhemoglobin (COHb) was determined for the South of Minas
      Gerais. MATERIAL AND METHOD: The COHb was analyzed by the Beutler and West (1984)
      spectrophotometric method, optimized in our laboratory. In all the samples,
      analyses of some biochemical and hematological parameters were made to evaluate
      the health condition of a population of 200 volunteer non-smokers occupationally
      not exposed to CO. Each individual answered a questionnaire to obtain data
      pertinent to the interpretation of the results. The reference values were
      expressed as mean values +/- standard deviation, with a 95% confidence interval,
      and an upper reference value. The statistical distribution of the results was
      made so as to enable comparisons between the results of groups of workers, rather
      than individual evaluations, to be made. RESULTS AND CONCLUSIONS: The mean value
      +/- standard deviation was 1.0% +/- 0.75; the 95% confidence interval was 0.9
      1.1% and the upper reference value was 2.5%. By the t Student test (p < or =
      0.05), no difference was detected between the values related to sex, age or
      ingestion of alcoholic beverages. The reference values obtained were close to
      those reported for others countries.

PMID- 9629718
TI  - [Defining priorities for the management of health science and technology].
AB  - INTRODUCTION: An urgent need for the management of science and technology
      production in the health field has been recognised in Brazil since 1994, when the
      Federal Government called a National Conference on the subject. The present study
      presents a methodology for the identification of items of priority in planning
      such management. MATERIAL AND METHOD: A survey was conducted in the research
      institutes belonging to the S. Paulo State Health Department among a sample of
      research professionals with a view to collecting data on two different scenarios:
      present and expected situation. Eighteen concepts, assembled in four different
      groups, were assessed is terms of an average percentage approval or disapproval,
      for each scenario. Consistency for the measurement of each of these groups was
      examined by the use of Cronbach's alpha coefficient and inconsistent concepts
      were disregarded in the analysis. The average percentage of approval/disapproval
      was further calculated as scenario co-ordinates for each concept and institute
      entering the study so that priority maps for concepts and institutes could be
      constructed. RESULTS: Results suggest that the present situation meets with
      disapproval, though not strongly so, while a high degree of expectation is
      expressed with significant emphasis as regards research infrastructure
      management. The main priorities are given as: acknowledgement of performance,
      support for publication, resource allocation by research project and
      methodological advice for research analysis. CONCLUSION: It is concluded that the
      study methodology was helpful in eliciting management priorities and could be
      applied elsewhere with due adjustment of content regarding selection of concept
      and their grouping.

PMID- 9629719
TI  - [Update on the geographical distribution and first record of Lutzomyia
      longipalpis in an urban area in Sao Paulo State, Brazil].

PMID- 9629720
TI  - Susceptibility of asthmatic children to respiratory infection.
AB  - OBJECTIVE: A case-control study of patients with pneumonia was conducted to
      investigate whether wheezing diseases could be a risk factor. METHODS: A random
      sample was taken from a general university hospital in S. Paulo City between
      March and August 1994 comprising 51 cases of pneumonia paired by age and sex to
      51 non-respiratory controls and 51 healthy controls. Data collection was carried
      out by two senior paediatricians. Diagnoses of pneumonia and presence of wheezing
      disease were independently established by each paediatrician for both cases and
      controls. Pneumonia was radiologically confirmed and repeatability of information
      on wheezing diseases was measured. Logistic regression analysis was used to
      identify risk factors. RESULTS: Wheezing diseases, interpreted as proxies of
      asthma, were found to be an important risk factor for pneumonia with an odds
      ratio of 7.07 (95% CI = 2.34-21.36), when the effects of bedroom crowding (odds
      ratio = 1.49 per person, 95% CI = 0.95-2.32) and of low family income (odds ratio
      = 5.59 against high family income, 95% CI = 1.38-22.63) were controlled. The risk
      of pneumonia attributable to wheezing diseases is tentatively calculated at
      51.42%. CONCLUSION: It is concluded that at practice level asthmatics should
      deserve proper surveillance for infection and that at public health level
      pneumonia incidence could be reduced if current World Health Organisation's
      guidelines were reviewed as to include comprehensive care for this illness.

PMID- 9629721
TI  - Cross-cultural differences in children's concepts of health and illness.
AB  - INTRODUCTION: In spite of general agreement that cross-cultural research is
      needed in the health area, most existing investigations of children's development
      of health and illness-related concepts have involved samples from developed
      countries. The study examined the development of the concepts of health and
      illness as a function of subject's age, socio-economic status (SES), gender and
      grade level in a Brazilian sample of 96 elementary and junior high school
      students. METHODS: Subjects were interviewed individually and their ideas of
      health and illness were assessed through open-ended questions. Participants'
      answers were transcribed verbatim and subjected to content analysis. RESULTS: Chi
      square analyses revealed significant age, school grade and SES-related
      differences in participants' concepts of health and illness. DISCUSSION AND
      CONCLUSION: The themes employed by subjects to define both health and illness
      were broadly consistent with those found by previous research. The study showed a
      predictable relationship between subject's age and school grade level and
      increasingly more highly differentiated and multidimensional concepts of health
      and illness. This investigation suggests that, for the most part, cross-cultural
      similarities in children's concepts of health and illness may be more striking
      than the differences.

PMID- 9629722
TI  - [Characteristics of neonatal mortality in the State of Rio de Janeiro, Brazil, in
      the 1980's: a spatio-temporal analysis].
AB  - OBJECTIVE: The spatial distribution of neonatal mortality by age-group (0-23
      hours, 1-6 days and 7-27 days) in the State of Rio de Janeiro, Brazil, for two
      periods of time 1979-81 and 1990-92, is analysed. METHODOLOGY: A methodology was
      used to perform the spatial analysis which took the counties of Rio de Janeiro as
      the spatial units and "first-nearest-neighbors" as the neighborhood criterion.
      For the purpose of detecting anisotropy, the connection matrix was defined
      through "first-nearest-neighbors" in a particular direction. To understand the
      spatial behavior of neonatal mortality, social and environmental indicators and
      indicators of medical assistance by county for both periods of time were
      constructed. RESULTS AND CONCLUSIONS: At the beginning of the 80's, the neonatal
      mortality for the age group 7-27 days showed the presence of clusters in the East
      and Southeast in direct association with the poorest conditions of life in the
      State, characteristics that had vanished by the next decade. Spatial dependence
      for the mortality rates for the first day of life, for 1991, was identified
      clusters in two different regions beings detected, followed by a positive
      correlation with "number of private hospital beds per inhabitant". Some of the
      cluster counties were, in particular, death receivers from neighboring counties
      and showed hospital case fatality rates much greater than the overall mean rate.

PMID- 9629725
TI  - [Hospital assistance as an indicator of social inequality].
AB  - OBJECTIVE: To test a model for the study of inequalities in hospitalizations in
      the city of Ribeirao Preto (SP), understanding them to be due both to the social
      position of inpatients and also to health care policies in Brazil. MATERIAL AND
      METHOD: Using a hospital information system in existence for more than 25 years
      in the city of Ribeirao Preto-SP, 56.293 hospitalizations of municipal
      inhabitants occurring in some of the 12 general hospitals in 1993, were studied.
      Using the Brazilian occupancy classification for mortality, these inpatients were
      grouped on 6 occupational levels, as in the British classification: professional,
      intermediate, qualified non manual, qualified manual, partially qualified and
      unqualified. RESULTS AND CONCLUSIONS: Two-thirds of the inpatients had no place
      in the i.e. did not belong to the economically active population--and consisted
      of housewives, pensioners, children and students--and one third had some economic
      activity and thus belonged to the economically the active population. A close
      association was found between social strata and the classification of the
      hospital financing system into private, private group clinic and public health
      system patients. There were differences in hospital parameters as well as in
      morbidity patterns between these groups. The inequalities relating to average
      age, average age of hospital deaths, mean lengths of stay, hospital mortality, re
      internment and frequency of diseases are discussed. This model allows the social
      position of the inpatient to be estimated using the hospital financing system,
      including also those patients with no economic activity, which covers the
      majority of the population. Social mechanisms created to compensate for
      inequalities in the welfare state do not cancel out the social differences.

PMID- 9629724
TI  - [Use of manual vacuum aspiration in reducing cost and duration of hospitalization
      due to incomplete abortion in an urban area of northeastern Brazil].
AB  - INTRODUCTION: In most developed countries vacuum aspiration has been shown to be
      safer and less costly than sharp curettage (SC) for uterine evacuation. In many
      of the developing countries, including Brazil, sharp curettage (SC) is the most
      commonly used technique for treating cases of incomplete abortion admitted to
      hospital. The procedure often involves light to heavy sedation for pain control
      and an overnight hospital stay for patient recuperation and monitoring. Two
      hypotheses are examined: the first, that the use of manual vacuum aspiration
      (MVA)--a variation of the vacuum aspiration, would be less costly than SC for the
      treatment of cases of incomplete abortion admitted to hospital; and the second,
      that the treatment of incomplete abortion with MVA would substantially reduce the
      length of hospital stay. METHODOLOGY: Thirty women with diagnosis of first
      trimester incomplete abortion were randomly allocated to the SC or MVA group.
      Rapid-assessment data collection techniques were used to identify factors that
      contributed to cost reduction and hospital stay. RESULTS AND CONCLUSION: The
      results of the study show that, overall, patients treated for incomplete abortion
      with MVA spent 77% less time in the hospital and consumed 41% fewer resources
      than similarly diagnosed patients treated with SC. Recommendations are made as to
      the need of certain changes in patient management. Particularly necessary is
      information regarding cultural perception and concepts of abortion treatment.

PMID- 9629723
TI  - [Atherosclerotic cardiovascular disease, lipemic disorders, hypertension, obesity
      and diabetes mellitus in the population of a metropolitan area of southeastern
      Brazil. III--Hypertension].
AB  - OBJECTIVE: The prevalencies of hypertension are analysed by sex and age group, in
      social groupings established in accord with social criteria. With a view better
      to understanding the social dimension of the disease, prevalencies were
      characterised by type of occupation. MATERIAL AND METHODS: The sample consisted
      of 1,041 people and corresponds to the sum of the samples representing the "study
      areas" established by the use of socio-economic and geographical criteria. Four
      social strata were defined in obedience to a socioeconomic gradient. Hypertension
      was defined by the Joint National Committee (JNC), 140/90 mmHg, and of the World
      Health Organization (WHO), 160/95 mmHg, standard references. RESULTS: According
      to the JNC and WHO standard references the prevalencies of hypertension, age
      adjusted, were of approximately the following: stratum (I + II) 60 and 37%;
      stratum III 50 and 39%; stratum IV 55 e 46%. Among women the prevalencies were 40
      and 38% (stratum I + II); 56 and 47% (stratum III) and 55 and 46% (stratum IV).
      For the men belonging to the economically active population, classified by
      occupation, it was showed that the freelance professionals, consisting of
      businessmen of small firms, small traders and liberal professionals, presented a
      prevalence of about 60 and 37%; the skilled workers, employed in factories of 35
      and 14%; the daily freelance workers, unskilled laborers and unemployed, of 59
      and 40%. The women were divided by occupation as belonging or not to the
      economically active population (EAP) and presented the following prevalencies: 39
      and 47%, respectively, according to the JNC standard, and 27 and 45%,
      respectively, according to the WHO standard. Thus it may be seen that these
      results run counter to the hypothesis that women integrated into the labour
      market are more exposed to the risk factors for non-transmissible diseases.
      CONCLUSION: Thus it may be concluded that the categories most affected by the
      present economic were those most affected by hypertension. On the other hand the
      possibility of there being and a intense social determination in the etiology of
      hypertension in this population is demonstrated.

PMID- 9629726
TI  - [Relationship between pathogenicity of Schistosoma mansoni in mice and the
      susceptibility of the vector mollusk. IV--Infectiousness of miracidia].
AB  - OBJECTIVE: The infection ability of miracidia of BH and SJ strains of S. mansoni,
      obtained from mice infected with cercariae taken from Biomphalaria glabrata and
      Biomphalaria tenagophila, genetically selected for susceptibility is compared
      with the infection ability of miracidia obtained from mice infected with larvae
      from non-selected mollusks. MATERIAL AND METHOD: Progeny of S. mansoni resulting
      from successive infections of selected mollusk sproduced various generations of
      selected miracidia. Selection of B. glabrata and B. tengophila was carried out by
      autofertilization of mollusks susceptible to the BH and SJ strains of S. mansoni.
      Five generations of mollusks (from parental down to F4), were used in the
      experiment. Tests for the infectiousness of the miracidia used 10 larvae:
      susceptibility was checked starting on day 30 after infection, for 90 days,
      through observation for the presence of cercariae. RESULTS: The results showed
      that susceptibility of the selected mollusks in the face of the respective
      sympatric strains was not altered by the selection process of S. mansoni. However
      F4 miracidia of the BH strain were more infectant for non-selected B. glabrate
      than parental miracidia of the same strain. Miracidia of BH and SJ strains,
      parental generation, and BH strain, F3 generation, showed the same infectiousness
      in selected B. glabrata. Nevertheless, these mollusks had distinct infection
      rates from allopatric selected miracidia (SJ strain, F4 generation). The
      generation of successive infections of S. mansoni SJ in selected B. tenagophila
      resulted in the adaptation of the worm strain to the species of mollusk. B.
      tenagophila was never susceptible to the BH strain, even when selected mollusks
      and trematodes were employed. The susceptibility/infectiousness of the pair B.
      tenagophila-SJ S. mansoni strain was only changed by the selection process of the
      mollusks. CONCLUSION: As non-selected B. glabrata were more intensively infected
      by selected BH miracidia than by non-selected BH miracidia, one is led to surmise
      that the greater pathogenicity of S. mansoni from susceptible mollusks implies
      the greater infection ability of these miracidia.

PMID- 9629727
TI  - [Speech-language idiopathic disorder prevalence in children from one to eleven
      years of age].
AB  - OBJECTIVE: The study of the epidemiological aspect of speech-language idiopathic
      disorders. The profile relates to the prevalence rate among children from 1 to 11
      years old. METHOD: The subjects were assessed with regard to speech, language and
      myofunctional oral aspects. After diagnosis, the subjects were classified
      according to their principal disorder. Then the disorders were placed in separate
      age groups. The prevalence rates were applied. RESULTS: The sample for this study
      included 2,980 children, 125 with primary communicative disorders (prevalence
      rate = 4.19). The highest general prevalence related to the 3 to 8 year old age
      group. The critical phase was that from 4 to 5 years of age. The most prevalent
      idiopathic speech-language disorders were: articulatory disorders; then oral
      language delays and myofunctional and neurovegetative disturbances. DISCUSSION:
      It is important to note that the communication disorder prevalence rate is very
      significant during childhood. It is a serious problem in Brazil, because although
      we have more critical cases there are no national preventive programs for these
      pathologies. It is, therefore, expected that this problem will increase rapidly
      in the near future if there isn't governmental action.

PMID- 9629729
TI  - [Reproducibility of data in a study of the risk factors for insulin-dependent
      diabetes mellitus].
AB  - The reliability of information about mothers' and fathers' education, weight and
      height at birth, history of diarrhoea, duration of exclusive breast feeding and
      age of introduction of cows' milk products, selected from a structured
      questionnaire used in home interviewers was examined in a sample of 38 cases and
      38 controls from a study related to the risk factors of insulin-dependent
      diabetes mellitus. The repetition of the questions was done by telephone. The
      agreement between the answers of both interviewers was verified using the kappa
      statistic (categorical variables) and the intra-class correlation coefficient
      (quantitative variables). The results enable one to conclude that the information
      is reproducible.

PMID- 9629728
TI  - [Humoral immune response of dogs to the inactivated suckling mouse brain vaccine
      used in anti-rabies campaigns in Brazil].
AB  - INTRODUCTION: An anti-rabies campaign is undertaken annually in Brazil with of
      the Fuenzalida & Palacios vaccine. The humoral immune response of dogs vaccinated
      during the campaigns was researched with the objective of evaluating whether the
      dogs presented a protective titer (0.5 UI/ml) 12 months after vaccination and how
      many of these achieved this titer 30 days after a buttressing vaccination.
      MATERIAL AND METHOD: Three hundred and forty-one specimens of serum of dogs
      domicilied, 259 in the S. Paulo and 82 in the Paulinia counties, were analyzed
      utilizing the Rapid Fluorescence Focus Inhibition Test. The immune response was
      evaluated taking into consideration the nutritional state of the animal and the
      number of previous vaccinations. RESULTS: The larger number of the dogs had not
      achieved the 0.5 UI/ml titer after 12 months, independently of the nutritional
      state and the response to the buttressing vaccination was more apparent in dogs
      with two or more previous vaccinations. DISCUSSION: The cut off of 0.5 UI/ml as
      protective titer in dogs and the influence of the nutritional state and health
      conditions of the animals as responsible for humoral immune response are
      discussed.

PMID- 9629730
TI  - [Phlebotomine sandflies and domestic animals interaction and Lutzomyia
      (Nyssomyia) intermedia (Lutz & Neiva, 1912) predominance in an area with a high
      level of anthropy, in southern Brazil].
AB  - Information on phlebotomine collections in an area with a high level of human
      interference, in S. Jorge do Ivai county, Parana State, Southern Brazil, is
      reported. Lutzomyia (Nyssomyia) intermedia (Lutz & Neiva, 1912) was the dominant
      species. The number of sandflies in domiciles decreased sharply in the second
      period of collection. This occurred because a pigsty was moved to a distance of
      approximately 100 meters from the houses by and because the basement of one the
      houses was cleaned out.

PMID- 9629731
TI  - [Aedes (Stegomyia) albopictus (Skuse) breeding in Bromeliaceae in the outskirts
      of an urban area of the city of Sao Paulo, Brazil].
AB  - Larvae of Aedes albopictus from a plant of the Bromeliaceae family on the
      outskirts of S. Paulo, SP, Brazil, were collected. This occurrence sheds new
      light on the attempt to determine the potential of this plants as a breeding site
      for this mosquito in Brazil.

PMID- 9629732
TI  - [Breeding places of Aedes scapularis (Diptera: Culicidae) in artificial
      containers].
AB  - Breeding places of Aedes scapularis were found in the Ilha Comprida and Pariquera
      Acu counties of S. Paulo State, Brazil. They included several types of artificial
      water container. As 270 (250 larvae and 20 pupae) immature forms were collected,
      the hypothesis is raised that behavioral change is occurring as a secondary
      adaptation, as a consequence of the anthropic environment. This tends toward a
      reduction in ground breeding places and, at the same time, to an increase in the
      number of artificial containers. So the synanthropic tendence of thus mosquito
      may be favored by or even be a result of the man-made environment. Reference is
      made to the epidemiological consequences of this phenomenon for encephalitis
      transmission specifically for the Southeastern region of Brazil.

PMID- 9629733
TI  - [Implications of spatial aggregation of parasites for the population dynamics in
      host-parasite interaction].
AB  - Some aspects of the widely observed over-dispersed pattern of the distribution of
      parasites within the host population are examined. It has been established in the
      parasitological literature that most hosts usually harbour few parasites, while
      only few hosts harbour a large proportion of the parasite population. Factors
      that may influence the pattern of distribution of parasites, the relation between
      the level of parasite aggregation and the prevalence of infection, and changes in
      this level of aggregation as a function of host age are analysed. Factors which
      determine the diversity of species in parasite communities are presented, and
      aspects of exploitative and interference competition among parasites and their
      relations with biological control procedures are also considered. Attention is
      also focused on the regulatory and destabilizing processes influencing the
      dynamic behaviour of host-parasite population interactions.

PMID- 9629734
TI  - [The challenge of emergent diseases and the return to descriptive epidemiology].
AB  - The definition of emergent and re-emergent diseases, patterns of occurrence
      during the last 25 years, and the determinants of this occurrence are presented.
      The importance of descriptive epidemiology and its use in the investigation of
      these health problems, especially in view of epidemiologists' tendency to give
      less attention to it, finally, is emphasized the challenges that the emergent
      diseases pose for public health practice and for the methodological development
      of descriptive epidemiology are also set out. These challenges are considered in
      three fields: biosecurity, surveillance systems and descriptive epidemiology
      techniques.

PMID- 9629735
TI  - [The concept of health].
AB  - Objections to the present WHO (World Health Organization) definition of HEALTH,
      as "the state of perfect physical, mental and social well-being", are expressed.
      It is considered to be anachronistic, first because it aims at perfection which
      is unaltainelle because of district personality characteristics. As the main
      support for this idea, the necessary renunciation of part of man's drive to
      liberty in exchange for the lesser insecurity provided by social life (Freud,
      Castoriadis and McDougall), is groted. The validity of distinguishing between
      "soma", "psyche" and "society" is questioned and the concept of the "integrated
      man", alluding to Pierre Marty and to Freud himself is adapted, and situations
      are recalled in which the interaction of the three aspects mentioned above is
      actually evident. Finally, the notion of the quality of life, in accordance with
      an antipositivistic taken from Bion, point of view, is discussed, and the concept
      that reality is that of each human being, is adapted. This priority and the
      proposal to rescue subjectivism which was also observed by Foucault when he
      studied mental disease, leads to a last criticism of the present definition of
      health, based exclusively on external, objective evaluations.

PMID- 9629736
TI  - [Results of the surgical treatment of non-complicated pilonidal disease].
AB  - In spite of the high incidence of pilonidal disease at young population and
      prolonged disabling period that it demands, colorectal surgeons have not reached
      consensus about etiology or best treatment for this condition. The authors intend
      to analyse results from 154 cases operated on at HCFMUSP through a retrospective
      chart analysis regarding patients' sex, age and race, operative technique,
      complications and recurrence. Half patients were male. Eighty-three percent were
      between 11 and 30 yr-old. Incision and curettage was offered to 74.7% of the
      patients. Excision technique was used in 25.3%. In patients who underwent
      excision technique, there were no recurrences and a cicatrization defect was
      diagnosed in 2 (5.1%) patients. For patients who underwent incision and
      curettage, recurrence was 3.5% and cicatrization defect was seen in 1 (0.9%)
      case. Excision or incision plus curettage techniques seem to be both effective
      for treatment of chronic pilonidal disease although the former may produce
      healing defect more commonly. Patients who present with complex lesions may
      benefit from excisional techniques associated to skin or myocutaneous flaps in a
      first attempt instead of conservative approaches.

PMID- 9629737
TI  - [Risk factors of stroke in carotid endarterectomy].
AB  - In order to find risk factors of carotid endarterectomy related stroke (CERS),
      102 consecutive carotid endarterectomies, performed within two years on 95
      patients were analyzed. Age, sex, diabetes, smoking, hypertension, degree of the
      operated and non operated carotid stenosis, previous neurological symptoms,
      anesthesia, protamine, cerebral monitoring, shunt, patch, post op. hypertensive
      crisis and clamping time were compared with the incidence of CERS. Four patients
      had major neurological deficits, two of which were fatal (3.92%). Six patients
      had minor transitory neurological deficit (5.8%). The use of patch and a long
      clamping time were the only identifiable statistically significant factors (p =
      0.016 and p = 0.0053 respectively) that increase the odds of a CERS.

PMID- 9629738
TI  - [Prevalence of fecal incontinence in diabetic patients: epidemiological study of
      patients assisted as outpatients at the Clinical Hospital of the Medical School
      at the University of Sao Paulo].
AB  - The object of this research was to establish the prevalence of fecal incontinence
      in those diabetics attended as outpatients at the Hospital das Clinicas da
      Faculdade de Medicina da Universidade de Sao Paulo. Individual verbal
      interviewing was the an adopted method. The classification of diabetes mellitus
      of World Health Organization was employed (1985). Data was aggregated relative
      sex, age, color, type of diabetes mellitus, fecal incontinence, duration of
      diabetes mellitus, peripheral neuropathy, intestinal habits (normal, constipation
      and diarrhea), urgency to evacuate, sensation of incomplete evacuation, urinary
      incontinence, vaginal deliveries and its characteristics. The study involved 258
      diabetics, 167 of female sex having an average age of 56.2 years (17 to 78 years
      of age) and 91 of the male sex having average age of 55.8 years (10 to 74 years
      of age). With relation to color, 57% were white, 28.7% mullato, 11.2% black and
      3.1% yellow. Fecal incontinence was prevalent in 18.6% of the cases studied. It
      occurred also in types I and II diabetics with predominance in the male sex. It
      also occurred in diabetics having an average history of 10.8 years to onset of
      illness. Peripheral neuropathy was observed in 8.5% of the diabetics investigated
      however no association was observed between the peripheral neuropathy and fecal
      incontinence. Constipation occurred in 29.5% of the patients and diarrhea in
      21.3%. Incomplete evacuation was apparent in 15.1% of diabetics and urgency to
      evacuate in 12.8%. A relationship was identified between fecal incontinence with
      diarrhea and incomplete evacuation in the group investigated. Total vaginal
      deliveries was 458 with 70 episiotomies and 25 by forceps. There was no
      statistical evidence of association between the average number of vaginal
      deliveries, episiotomies and forceps in diabetics demonstrating or not
      demonstrating fecal incontinence. Urinary incontinence was more prevalent that
      fecal incontinence. No relationship was determined between urinary and fecal
      incontinence for the purpose of the present study.

PMID- 9629739
TI  - [Videolaparoscopic treatment of hepatic single cysts].
AB  - We report a study of 6 patients with simple hepatic cyst. All were underwent
      laparoscopic surgical treatment. The median age of patients was 66 years, 5 women
      and 1 man were in the series. Cyst diameters varied from 3 to 15 cm. The
      treatment of choice is laparoscopic fenestration and resection of external part.
      There were no complications in postoperative period and the follow-up results are
      encouraging.

PMID- 9629740
TI  - [Complications of chronic pancreatitis in Sao Paulo (Brazil)].
AB  - Chronic Pancreatitis (CP) presents distinctive characteristics in different
      geographical areas. With the purpose of evaluating the clinical characteristics,
      particularly in relation to the frequency and etiopathogeny of the complications
      in Sao Paulo, in comparison to other centers, 545 patients with this disease were
      analyzed, retrospectively, 493 (90.5%) of these patients were males and 52 (9.5%)
      females, with ages ranging from 8 to 88 (38.2 +/- 9.3 years). The diagnosis of CP
      was based on criteria previously adopted by the Pancreas Group of
      Gastroenterology Studies of the Medical School of Sao Paulo. The principal
      etiologic factors were represented by: chronic alcoholism in 509 of the 545
      patients (93.4%), hereditary factors in four (0.7%), malnutrition in three
      (0.5%), metabolic alterations in three (0.5%) and obstruction to the pancreatic
      flow in two patients (0.3%). In 24 (4.4%) of the 545 patients, the etiologic
      factor could not be established, due to the idiopathic nature of the disease. Of
      the 509/545 patients (93.4%) presenting chronic ethylism, alcoholic consumption
      was characterized by: a) mean age alcoholic consumption was initiated: 19.5 +/-
      6.5 years; b) mean daily alcoholic consumption in grams of pure ethanol: 358.6 +/
      282.0 g/d; c) mean time of alcoholic consumption: 19.8 +/- 8.8 years, and d)
      mean age of the appearance of clinical symptoms: 34.9 +/- 9.8 years. The clinical
      complications were always investigated in accordance with the pre-established
      protocol; the principal complications observed were represented by:
      gastrointestinal compression (3.3%), jaundice (24%), cysts (35.9%), cavity
      effusions (13.3%), pancreatic necrosis (4.7%), abscesses (3.6%), digestive
      hemorrhage of pancreatic origin (2.3%) and fistulae (1.1%). The incidence of
      these complications, particularly cysts, cavity effusions and pancreatic
      necrosis, was greater in the patients studied than in those observed in other
      regions, probably due to the presence of more intense and frequent
      anatomopathologic lesions found in these patients, possibly resulting from the
      greater consumption of alcohol compared to patients with this disease in other
      centers. The etiopathogenic mechanisms for the complications were individually
      analyzed and interpreted.

PMID- 9629741
TI  - Experimental toxoplasmosis, and immunosuppression (parasite evaluation and
      histological alterations)
AB  - With the purpose of studying immunosuppressant drug action on parasites, the
      effect of Cyclosporine and cortisone in experimental toxoplasma evaluation, a
      highly virulent strain of Toxoplasma gondii (RH strain) was used. The animals
      were divided in two groups: control and immunosuppressed. Two animals from each
      group were sacrificed daily. Evaluation was based on parasitemia and parasitism
      of peritoneal exsudate and presence of the parasite in heart, lung, liver,
      spleen, small bowel, brain, cerebellum, spinal cord and eyes. Parasite
      infestation in peritoneal exsudate was 10 times greater than parasitemia. Red
      spots were observed after the second day; after the fourth day, focal necrosis
      with softening and fluidification of brain tissue spattered throughout the
      nervous tissue with enhanced vascularization. Capillaries obstructed by
      Toxoplasmas gondii were found, causing infarction and necrosis due to toxic or
      enzymatic substances. Images suggestive of cells an "owl-eye", Cytomegalovirus
      like were found, with T. gondii, both in the brain, as well as in the tear glands
      and small bowel. Blood stream parasite infestation was observed, no
      histopathological lesions were found in the remaining tissue, possibly due to
      lack of time, for all animals died within a week's observation. We conclude that
      immunosuppression has worsened the outcome, anticipating the disease in 24 hours.

PMID- 9629742
TI  - [Duodenal duplication in adult simulating pancreas pseudocyst].
AB  - An adult patient with clinical and radiologic evidence of pancreas pseudocyst was
      undergone at laparotomy and a diagnosis of duodenal duplication was made. Due to
      the rarity of this case, a review of the literature is presented and the authors
      discuss the treatment of duodenal duplication.

PMID- 9629743
TI  - [Videolaparoscopic cholecystectomy in a patient with Mirizzi's syndrome].
AB  - We present a case report of laparoscopic cholecystectomy in patient with
      Mirizzi's syndrome. A 48-year-old woman with symptomatic cholelithiasis underwent
      laparoscopic cholecystectomy. During the procedure we found an unexpected type I
      Mirizzi's syndrome. Meticulous dissection was needed to avoid injury to the
      biliary tract. The postoperative course was uncomplicated and she was discharged
      on the second postoperative day.

PMID- 9629744
TI  - [Captopril use in pregnancy and its effects on the fetus and the newborn: case
      report].
AB  - Angiotensin-converting enzyme (ACE) inhibitors have been widely used to control
      hypertension, but their use during gestation may result in fetal death, intra
      uterine growth retardation, oligoamnium sequence, hypotension, acute renal
      failure and ductus arteriosus patency in the newborn. The aim of this case report
      is to highlight the risks of using this drug during gestation. The authors
      present a case of captopril use during pregnancy, whose newborn developed acute
      renal failure and ductus arteriosus patency early in the newborn period. This
      presentation strengthens the importance of not only monitoring amniotic fluid
      volume and fetal growth, but also, during the newborn period, control the weight
      gain, diuresis, systemic arterial pressure and renal function, mainly in the
      first 72 hours of life.

PMID- 9629745
TI  - [Magnesium and myocardial infarction. Brazilian aspects].
AB  - Most of the brazilian's territory is poor in magnesium (Mg) and an evaluation of
      urinary Mg indicated very low concentration of this cation in a normal population
      sample. The study of the behavior of plasmatic Mg in the acute phase of
      uncomplicated myocardial infarction permitted the following conclusions; a)
      during the first three days of the clinical course there is significant
      hypomagnesemia; b) magnesemia rises progressively during the three days of
      infarction, without however reaching normal levels. The lymphocytic magnesium
      also show the same behavior. Mg infusion in patients with acute myocardial
      infarction (four grams of MgSO4 during the first three days) reduced the
      incidences of arrhythmias, death and the size of infarction, in Sao Paulo.
      Another study in Bahia also showed reduction of mortality with infusion of 10
      grams of MgSO4 in 24 hours. These studies about the protective role of Mg show
      potential limitations because the samples were small.

PMID- 9629746
TI  - [The teaching of anatomy: a student view].
AB  - This article contributes to the discussion of the Base Cycle discipline syllabus
      reformulation, specifically on the Anatomical field, at Sao Paulo University.
      Based on student board opinion poli, this article establishes objective
      indicators for teaching improvement of those disciplines, in a comparative manner
      to the faculty board conception.

PMID- 9629747
TI  - [Teacher's opinions regarding graduation programs at the University of Sao Paulo
      Medical School--PAC-II].
AB  - The authors show the results of the "Curricular Evaluation Program" of University
      of Sao Paulo Medical School pertaining to the year of 1996. This program (PAC-II)
      is based on teachers' opinions regarding the subjects taught (1st to 4th grades)
      and hospital intern courses. The opinions collected concerning such programs were
      definitely favorable. Most of the teachers considered the programs to be either
      good or very good. It was also identified that the hospital intern courses were a
      little more valued than the other courses taught in the first four grades.

PMID- 9629748
TI  - [Self-healing].
AB  - Based on the concept of: "Collective Unconscious", from C. G. Jung, the authors
      discuss the theme of the "Wounded-healer", as an archetype to enlighten the
      practice and the training of modern medicine. By the understanding of the deep
      meanings of the ancient myth of Asclepius (Esculapio) a solid help can be provide
      on the everyday problems of the relationship between doctors and theirs patients.

PMID- 9629749
TI  - [A tribute to professor Hector Croxatto Rezzio: setting up science in Chile.
      "Nature is always more amazing than our imagination can conceive"].
AB  - Hector R. Croxatto, M.D., has recently celebrated his 90th anniversary, fully
      active in scientific research and in other academic activities. Along his
      productive life, he has contributed with original observations on the role of
      certain peptides in the pathogenesis of arterial hypertension. Furthermore, he
      has been a leader in the development of biological research in Chile and the
      mentor or teacher of several prominent disciples who have had, or are having,
      their own brilliant careers in medicine and in science in Chile and other
      Latinamerican countries. Although most of his scientific productivity has been
      published in top journals in the international field, several of his papers have
      been published in Revista Medica de Chile. In this issue, the journal pays a
      tribute to this outstanding scholar, his exceptional personality and fruitful
      academic career. The tribute includes this Editorial, a Letter to the Editor and
      its reply, and his most recent manuscript, all testifying the exceptional virtues
      of a great man.

PMID- 9629751
TI  - [Association between maternal heterozygosity for five blood groups and
      reproductive success].
AB  - BACKGROUND: In man, blood groups are polymorphic genetic systems. Maternal fetal
      incompatibility phenomena should lead to an elimination rather than a maintenance
      of these polymorphisms. A possible mechanism that could explain the persistence
      of these polymorphisms in natural populations is a selective reproductive
      advantage of heterozygous individuals. AIM: To explore the relationship between
      maternal heterozygosity for five blood groups and some obstetrical variables
      related to gestational success. MATERIAL AND METHODS: Using a case control
      design, to every mother giving birth to a malformed child a consecutive mother,
      whose offspring was normal, was assigned as control. All women were typified for
      ABO, Rh, Kidd, MNSs and Duffy blood groups. RESULTS: Two hundred two women were
      studied. There was only one stillbirth, born from a heterozygous mother for all
      analyzed loci. Mothers that were heterozygous or homozygous for all loci had a
      higher frequency of malformed children. Women homozygous for all loci had a
      higher frequency of living offspring than the rest of the sample. CONCLUSIONS:
      Heterozygous mothers for these genetic systems have a reproductive disadvantage.

PMID- 9629750
TI  - [Resistance of human immunodeficiency virus (HIV) to zidovudine. Genotypic
      analysis in strains isolated from Chilean patients].
AB  - BACKGROUND: Resistance of HIV to AZT is the result of mutations in the pol gene
      that codifies the enzyme reverse transcriptase. AIM: To assess the resistance to
      antiretroviral drugs in Chilean patients infected with HIV. MATERIAL AND METHODS:
      The presence of mutations was searched in 22 patients infected with HIV. The
      emergence or persistence of these mutations was studied in sequential samples of
      19 patients. The presence of the mutation that confers resistance to didanosine
      (DDI) was studied in those subjects exposed to the drug. Polymerase chain
      reaction techniques were used to analyze mutations in codons 41, 70 and 215 of
      the pol gene (resistance to AZT) and the mutation in codon 71 (resistance to
      DDI). RESULTS: On admission, none of the patients without previous exposure to
      AZT had drug resistance mutations. Seven of 12 patients (58.3%) that had received
      AZT had mutations in codon 215. In two, they were associated to a mutation in
      codon 41 and in two, a mutation in codon 70. After a mean follow up of 14 months,
      13 of 15 patients (86%) that received AZT had viral strains genotypically
      resistant to the drug. In nine of these, the resistance was associated with
      disease progression. None of the 10 patients that received DDI had the mutation
      in codon 74 that confers resistance to the drug. However, in one of these
      patients, that never received AZT, a virus with a mutation in codon 215 was
      detected. CONCLUSIONS: A high percentage of patients that have received
      monotherapy with AZT have genotypic resistance to the drug. This resistance is
      associated with clinical and immunological derangement in 70% of these subjects.

PMID- 9629752
TI  - [Effects of bromocriptine in patients with active rheumatoid arthritis].
AB  - BACKGROUND: Neuroendocrine factors play an important role in the expression of
      autoimmune diseases. Prolactin (PRL) can induce T-cell proliferation and
      macrophage activation. Elevated PRL levels have been described in patients with
      rheumatoid arthritis (RA). AIM AND METHODS: We studied immunological and clinical
      effects of PRL suppression in 9 RA patients with active disease, treated for 3
      months with bromocriptine (BRC), an inhibitor of PRL secretion. RESULTS: BRC
      induced a significant depression of the peripheral blood mononuclear cells
      response to antigen (p = 0.008) and mitogen (p = 0.008) which was significantly
      correlated with improvements in the HAQ disability index (r = 0.68; p = 0.04) and
      grip strength (r = 0.7; p = 0.02). Also, the in-vitro production of IL-2, nitric
      oxide and poliamines--that are critical for the proliferative response of
      lymphoid cells--decreased significantly. The group experienced significant
      improvement of grip strength (p = 0.028) and the HAQ disability index (p =
      0.025), whereas 4 individuals achieved clinical improvement according to the
      American College of Rheumatology preliminary definition. We conclude that BRC
      treatment induces a significant depression of in-vitro immune function in RA
      patients and that these changes are related to parameters of disease activity.
      The effects of BRC on immune function and disease activity in RA patients warrant
      further investigation.

PMID- 9629753
TI  - [Tumor invasion in gallbladder cancer. Importance of blood vascular tumor
      infiltration diagnosis].
AB  - BACKGROUND: The infiltration of venous blood vessels in gallbladder carcinoma and
      its importance as a prognostic factor has not been well studied. Victoria blue
      stain has been used to identify vascular involvement in gastric and thyroidal
      carcinomas. AIM: To assess blood vessel infiltration using Victoria blue stain in
      gallbladder carcinomas. MATERIAL AND METHODS: One hundred forty eight samples of
      gallbladder carcinomas, coming from 24 men and 123 women aged 60.4 +/- 12.2 years
      old, were studied. They were stained with Victoria blue stain to quantify blood
      vessel invasion. RESULTS: Twenty nine percent of tumors had blood vessel
      infiltration, 61% had lymph vessel and 20% had perineural infiltration. Lymph
      vessel or perineural involvement was found in 81% and 31% of those tumors with
      blood vessel infiltration, respectively. Perineural infiltration was associated
      with lymph or vascular involvement in 93 and 40% of tumors, respectively. None of
      the early carcinomas had blood vessel infiltration, whereas 33% of advanced
      tumors had this type of infiltration (p < 0.001). No differences in vascular
      infiltration were observed according to the differentiation of the tumor.
      CONCLUSIONS: Blood vessel infiltration was observed only in advanced gallbladder
      carcinomas and was tightly related to the degree of gallbladder wall
      infiltration. The presence of perineural infiltration was the best marker of
      lymph or blood vessel infiltration.

PMID- 9629754
TI  - [Efficacy and tolerance of a five day course of ciprofloxacin in the treatment of
      urinary tract infection in women. Multicenter study].
AB  - BACKGROUND: There is no consensus about the ideal antimicrobial agent and
      duration of treatment for urinary tract infection in women. AIM: To assess the
      efficacy of a five days course of ciprofloxacin for the treatment of urinary
      tract infection in women. PATIENTS AND METHODS: Women with urinary tract
      infection were treated with ciprofloxacin (Baycip, Bayer) 250 mg bid during 5
      days. Patients were evaluated three to four days after treatment start, two to
      seven days and one month after treatment end. RESULTS: Of 101 eligible women, 96
      aged 18 to 65 years old, coming from three major Chilean cities, participated in
      the study and 80 completed the follow up period. There was a 95% clinical
      success, 2.5% partial improvement and 2.5% treatment failure. The causal
      microorganism was erradicated in 90% of cases, in 1.2% treatment failed and in
      8.7% a re-infection occurred. Adverse effects attributable to the drug were
      observed in 12 patients (headache in 3, gastrointestinal disturbances in 8,
      somnolence in 1 and irritability in 1). CONCLUSIONS: Ciprofloxacin is an useful
      antimicrobial for the treatment of lower urinary tract infection in women.

PMID- 9629755
TI  - [Quality control of bone densitometry: precision, reproducibility, and clinical
      application].
AB  - Dual energy x-ray absorptiometry (DEXA) is one of the most widely used methods
      for bone mineral density (BMD), total body mass (TBM), total body fat (TBF),
      percentage of total body fat (%TBF) and total body fat-free mass (TBFFM)
      measurements. We investigated the in vitro and in vivo accuracy and precision of
      DEXA in repeated measurements of a lumbar spine phantom and in 30 healthy
      volunteers. Based on precision, the minimal significant variability (MSV) at 95%
      confidence level between 2 measurements of the same object or subject was
      calculated. In vitro accuracy and MSV were 99.8 and 0.9% respectively. In vivo
      indexes were 99.4 and 0.9% for whole-body BMD, 98.6 and 2% for lumbar spine BMD,
      96.6 and 4.8% for femoral neck BMD, 98 and 2.8% for major trochanter BMD, 96 and
      5.7% for Ward's triangle BMD, 99.5 and 0.7% for TBM, 98 and 2.9% for TBF, 97.9
      and 3% for %TBF and 99 and 1.4% for TBFFM. Our findings indicate that DEXA is a
      very reliable instrument and in order to be 95% confident of a real change
      between 2 scans a difference of at least the calculated MSV must be measured.

PMID- 9629756
TI  - [Coronary surgery. 20 years of follow-up].
AB  - BACKGROUND: Since the first surgical coronary revascularization done in Chile in
      1971, 5000 such procedures have been performed. AIM: To assess the long term
      results of coronary revascularization surgery in our institution and to identify
      prognostic factors. PATIENTS AND METHODS: Five groups of 100 patients each,
      composed by the first consecutive patients subjected exclusively to coronary
      bypass surgery in the years 1975, 1980, 1985, 1990 and 1995 were retrospectively
      studied. RESULTS: Mean age of patients increased from a median of 52 years old in
      1975 to 62 years old in 1995. No changes in the frequency of diabetes,
      hypertension, high serum cholesterol or previous myocardial infarction were
      observed. There was an increase in the proportion of patients with a recent (< 30
      days) infarction that were operated along time. Seventy percent of patients had
      triple vessel disease or LMT and this proportion did not change. The number of
      grafts per patients increased form 1.9 to 3.4 and the use of arterial conduits
      from 0.18 to 0.81. Perioperative mortality remained constant and was 1.6%. Follow
      up information was obtained for 93% of 492 survivors. Actuarial survival at 5,
      10, 15 and 20 years was 93 +/- 1, 82 +/- 2, 62 +/- 3 and 41 +/- 4% respectively.
      Ninety eight +/- 0.7, 89 +/- 2, 73 +/- 4 and 65 +/- 5% of patients remained free
      of a new myocardial infarction in the same lapses, respectively. Ninety seven +/-
      1, 94 +/- 2, 76 +/- 4 and 47 +/- 7% of patients remained free of a new operation.
      Stepwise logistical regression analysis identified as bad prognostic factors, in
      decreasing order: cardiac failure, diabetes, smoking, hypercholesterolemia and
      age at the moment of operation. CONCLUSIONS: Coronary artery bypass surgery
      provides good and long lasting clinical improvement. The prognosis of patients is
      influenced by the presence of cardiac failure, some well known coronary risk
      factors and age at the moment of operation.

PMID- 9629757
TI  - [Negative appendectomy: experience at a university hospital].
AB  - BACKGROUND: Acute appendicitis still constitutes a difficult diagnostic problem.
      AIM: To assess the experience of an University Hospital in the diagnosis of acute
      appendicitis and to determine the rates of negative appendectomies. PATIENTS AND
      METHODS: The charts of 1,075 patients operated with the diagnosis of acute
      appendicitis, between 1993 and 1995, were retrospectively reviewed. All resected
      appendices were pathologically examined. Those cases in whom pathology did not
      confirm the clinical diagnosis were considered as a negative appendectomy.
      RESULTS: There was a 12.2% rate of negative appendectomies (18.9% in women and
      6.2% in men). The difference between sexes disappears in patients over 40 years
      old. In 49% of patients, no abnormality was detected during the laparotomy. The
      most frequent differential diagnosis were gynecological illnesses or diseases of
      the colon. DISCUSSION: The rate of negative appendectomies can be reduced with a
      close clinical observation of patients during their hospitalization and the
      judicious use of diagnostic laparoscopy.

PMID- 9629758
TI  - [Neuroradiological findings in 2 cases of Wilson disease with neurological
      involvement].
AB  - Wilson disease is an inborn error of copper metabolism that has neurological and
      hepatic manifestations. We report a 13 years old girl and a 12 years old boy with
      Wilson disease. In both patient, brain computed tomography and magnetic resonance
      imaging showed marked involvement of basal ganglia and other deep gray nuclei.
      Considering that this is a treatable disease, it should be included in the
      differential diagnosis of the so called "striatal necrosis of childhood".

PMID- 9629759
TI  - [Glucose in conjunction with peptides derived from kininogens might act from
      digestive tract as blockers of atrial natriuretic peptide mediated diuresis
      natriuresis].
AB  - This paper describes long term research efforts which have lead: 1) to the
      identification of peptides present in pepsanurin, a peptidic fraction obtained by
      pepsin hydrolysis of plasma globulins that inhibits the renal excretory action of
      atrial natriuretic peptide (ANP) and 2) to the discovery of an unexpected role of
      glucose, as a requisite for these inhibitory effects. The active peptides
      identified in pepsanurin are derived from plasma kininogens, substrates of the
      kallikrein-kinin system. Pro-kinins of 15, 16 and 18 amino acids, and bradykinin
      itself, block ANP-induced diuresis and natriuresis when injected i.v., i.p. or
      into the duodenal lumen of anesthetized rats in picomol doses. Furthermore, a
      novel 20 amino acids fragment derived from kininogen dominium-1, named PU-D1, is
      the most potent and longer lasting blocker of ANP renal effects. The anti-ANP
      effects of those peptides are prevented by B2-kinin receptor antagonists. The
      inhibition of ANP by kinins and PU-D1 was evident only in rats infused with
      isotonic glucose; whereas the excretory effect of ANP was not affected in fasted
      rats not infused, or infused with saline. These findings provide evidence that
      glucose facilitates liquid retention through a kinin-mediated inhibition of ANP
      excretory action that may be related to the prandial cycle.

PMID- 9629760
TI  - [Renal transplant and chronic rejection in pediatrics].
AB  - The rapid advances in immunobiology, pharmacology and molecular biology have made
      successful renal transplantation the optimal therapeutic modality for adults and
      children, reaching a near--90% of patient-graft survival among the first years of
      transplant. But this knowledge also presents clinicians and scientists with
      difficult challenges, one of the most important remaining is the chronic
      rejection of the graft. A critical review of the immunobiology, clinical
      evolution and histopathology of chronic rejection is presented. Immunosuppressive
      agents with emphasis in their mechanism of action is also detailed.

PMID- 9629761
TI  - [Laboratory surveillance of measles. Chile, 1992-1995].
AB  - BACKGROUND: The first massive national measles vaccination campaign in Chile was
      done in 1992. Since then a laboratory surveillance of the disease has been
      undertaken at the Instituto de Salud Publica. AIM: To report the results of
      laboratory surveillance of measles between 1992 and 1995. MATERIAL AND METHODS:
      Paired serum samples from suspected cases of measles were received at the
      Institute. Measles specific IgG was determined with indirect immunofluorescence
      methods. IgG and IgM immunoenzymatic methods were used as complementary
      techniques, and rubella infections were ruled out by hemmaglutination inhibition
      tests. RESULTS: Sera from 1087 presumptive cases (489 in 1992, 196 in 1993, 180
      in 1994 and 222 in 1995) were analyzed. Only two cases of wild imported measles
      were confirmed, one in Arica in 1992 and the other in Santiago in 1993. Five
      additional post vaccine cases were detected. Eighty eight percent of samples in
      1992 and 75% in 1994 were seropositive. A high percentage of cases were confirmed
      as rubella (55% in 1992 and 19% in 1994). CONCLUSIONS: Absence of wild measles
      virus circulation in Chile from 1992 to 1995 emphasizes the importance of
      laboratory surveillance of the disease.

PMID- 9629762
TI  - Drug-related biliary damage: a peculiar condition involving a genetic
      predisposition?

PMID- 9629763
TI  - The shift in prevalence of hepatitis A immunity in Flanders, Belgium.
AB  - The purpose of this study was to obtain data on the prevalence of hepatitis A in
      Flanders, Belgium, in order to analyse any change in the epidemiological pattern
      of hepatitis A virus (HAV) in the region, and to determine at which age pre
      vaccination testing would be useful. To meet these goals, a sero-epidemiological
      survey was conducted: 4058 serum samples were collected from a random sample of
      the general population in 1993-94. The overall age-standardised prevalence was
      51.3%. Among non-Belgians (N = 245), the age-standardised anti-HAV prevalence was
      66.4%, significantly higher than the 49.6% anti-HAV prevalence found in Belgians
      (N = 3186). Among Belgians, seroprevalence increased with age: from 5.4% in the
      youngest age group (0-14 years) to over 80% in the two oldest age groups (55-64
      years and > or = 65 years). Prevalence rates were as high as 31.7% in the 25-34
      year old age category, and 60.8% in the 35-44 year old age category. The age
      specific prevalence figures among Belgians and non-Belgians reflect two different
      epidemiological patterns: the epidemiological pattern of a low endemic region for
      Belgians and the epidemiological profile of an intermediate endemic region forn
      non-Belgians. The age-specific prevalence figures in Belgians were compared with
      the 1979 and 1989 anti-HAV prevalence figures in Belgian first-time blood donors.
      A clear epidemiological shift showing decreasing HAV prevalence in the youngest
      age groups was found. If we accept that pre-vaccination screening is useful at a
      35% prevalence rate, all persons over 35 years of age should be screened before
      vaccination.

PMID- 9629764
TI  - Follow-up of colon cancer: detection of liver metastases: benefit and
      periodicity.
AB  - The aim a follow-up programme in patients with cancer is to detect relapse or
      metastases in an early asymptomatic stage. This is only useful if the diagnosis
      of recurrence has implications for treatment and if early treatment of recurrence
      leads to an improved prognosis. This is certainly the case for liver metastases
      of colon cancer. Surgical resection of localised liver metastases has a 25-30% 5
      year survival. Early chemotherapy for non-resectable metastatic disease improves
      the survival and prolongs the symptom-free period in comparison with chemotherapy
      starting at the onset of symptoms. Follow-up for colorectal cancer should be
      offered to patients with the highest risk of recurrence and should consist of
      clinical examination, CEA monitoring, ultrasound of the liver, chest X-ray and
      periodic colonoscopy. Issues for further research are the determination of a
      follow-up programme with the highest sensitivity, the determination of the
      periodicity of follow-up, the search for prognostic factors for recurrence, cost
      issues and the final proof of a survival benefit in a large follow-up programme.
      CONCLUSIONS: Indirect evidence supports the need for a good follow-up programme
      for colorectal cancer focussing on the detection of liver metastases.

PMID- 9629765
TI  - Cost benefit of longterm follow-up of uncomplicated Crohn's disease.

PMID- 9629766
TI  - Mesenterico-left intrahepatic portal vein shunt: original technique to treat
      symptomatic extrahepatic portal hypertension.
AB  - MESENTERICO-LEFT INTRAHEPATIC PORTAL VEIN SHUNT: Original technique to treat
      symptomatic extrahepatic portal hypertension. OBJECTIVE: Revascularization of the
      intrahepatic portal system as decompressive surgery for chronic extrahepatic
      portal hypertension. SUMMARY BACKGROUND DATA: In patients with extrahepatic
      portal hypertension (portal trunk thrombosis in presence of a normal liver),
      shunt surgery is indicated when patient is bleeding from varices at a site not
      accessible for the endoscopist. Although surgical portal decompression is an
      efficient procedure, there is a risk of depriving the liver from the splanchnic
      venous flow and a risk of developing porto-systemic shunt related side effects.
      METHOD: A shunt was created between the superior mesenteric vein and the
      umbilical portion of the left portal vein. This technique allows to bypass the
      thrombosed portion of the portal vein but avoiding dissection of the cavernoma in
      the liver hilum and related risk of intraoperative hemorrhage. RESULTS: The
      procedure was successfully performed in one adult patient considered unshuntable
      in view of classic surgical procedures and in whom sclerotherapy was
      unsuccessful. This operation achieved an effective decompression of the
      splanchnic venous system. CONCLUSION: Rerouting the venous splanchnic flow
      through the liver was possible. It had the major physiological advantage of
      restoring the normal hepatic vascularization. It also avoided putting the patient
      at risk of developing porto-systemic shunt related side effects. This option
      should be considered when shunt procedures are indicated in patients with
      extrahepatic portal hypertension.

PMID- 9629767
TI  - [Cushing's syndrome].

PMID- 9629769
TI  - [Hepatic alterations in a model of alcoholism in the rat].
AB  - Today, there are a great number of investigations about alcoholism. The effects
      of alcohol had been studied in Medicine, Psychology, Biology, Biochemistry,
      Physiology or Pharmacology. Many investigations are carried out with humans,
      however, in most experiments is necessary to use animal models. Many experimental
      models of alcoholism in animals are usually used in the laboratories and they
      present several differences among them. In our investigation we have studied the
      hepatic alterations in an experimental model of alcoholism in the rat because the
      liver is a very sensitive organ which suffers the effects of alcohol and its
      metabolites. We try to demonstrate that there are hepatic lesions which allows
      the use of this experimental in the study of the behavioral and neural parameters
      in the rat. The experimental model of alcoholism that we propose has been
      considered appropriate to study the behavioral effects of alcohol, not only
      because the animals show the characteristic hepatic lesions, but also because
      they do not suffer manipulations that could alter them and as a consequence bias
      the behavioral data.

PMID- 9629768
TI  - [Cushing's syndrome: clinical study of fifteen cases].
AB  - OBJECTIVE: To study the epidemiological and clinical features and diagnostic
      tests of Cushing's syndrome (CS) of non-iatrogenic etiology, because of there are
      few similar studies in the last ten years. METHODS: Fifteen cases of CS were
      diagnosed from 1992 to 1997 at our hospital. We describe the epidemiological,
      clinical, biochemical, radiologic, therapeutic and evolutive characteristics.
      RESULTS: Both diabetes mellitus and hypertension were observed in 40% of
      patients. The frequency of etiologies was: Cushing's disease, 66.6%; ectopic ACTH
      syndrome, 13.3%; adrenal adenoma, 6.6%; adrenal carcinoma, 6.6%; and undiagnosed,
      6.6%. The 24-hour urine free cortisol (UFC) and the overnight 1 mg oral
      dexamethasone suppression test yielded 93.3 and 100% diagnostic sensitivity for
      CS, respectively. The overnight 8 mg oral dexamethasone suppression test, the
      metyrapone test and the 7 mg intravenous dexmethasone test had 75, 50 and 60%
      diagnostic sensitivity for Cushing's disease, respectively. Ketoconazole
      treatment had success in to normalize the 24-hour UFC in all patients, except for
      the case of adrenal carcinoma. CONCLUSIONS: The Cushing's disease was the most
      common form of CS. The 24-hour UFC and overnight 1 mg oral dexamethasone
      suppression test were good screening studies. Ketoconazole was successful in
      normalizing the adrenal cortex function.

PMID- 9629770
TI  - [Iatrogenic hyperthyroidism secondary to weight loss medication. Predictive
      factors for their precocious detention].
AB  - OBJECTIVE: To establish the differential clinical characteristics between the
      Iatrogenic hyperthyroidism for not conventional medication for obesity treatment
      (weight losers) and the endogenous by Graves Basedow disease. PATIENT AND
      METHODS: Observational and analytical study, populational based, in the one which
      prospectively were compared cases with Iatrogenic hyperthyroidism (secondary to
      weight losers) with those with endogenous hyperthyroidism (Graves Basedow
      disease) as controls. Consisted of the variable clinical record of 100
      correlative patients that consulted in specialized attention of endocrinology for
      Iatrogenic hyperthyroidism secondary to weight losers and for Graves Basedow
      disease. RESULTS: The differences observed between Iatrogenic hyperthyroidism
      (secondary to weight losers) (n = 43) as compared to endogenous hyperthyroidism
      (Graves Basedow disease) (n = 57) were: smaller age (31.8 +/- 10 as compared to
      37.8 +/- 12.6 years), greater body mass index (27.6 +/- 7.2 as compared to 23.4
      +/- 3.1), smaller goiter frequency (16.3% as compared to 84.2%) as well as
      absence of signs of ophthalmopathy (0% as compared to 57.9%). Both groups had low
      levels of TSH, and the difference rests in the values of free T4, low in the
      first group and increased in the endogenous hyperthyroidism. The odds ratio were:
      IMC > 27: 3.92 (0.91-16.72), age < 33 years: 5.58 (1.42-21.99), absence of
      goiter: 23.29 (6.39-84.85). The precedent of weight losers use was not selective
      of the first group, being detected in a 12.3% of cases of endogenous
      hyperthyroidism, though in periods of time remoter in relationship to the
      beginning of the clinic. CONCLUSIONS: In the differential diagnosis of a case of
      hyperthyroidism, it can be suspected Iatrogenic hyperthyroidism (secondary to
      weight losers) for medication for the obesity in patients of the feminine sex
      with overweight, without previous or familiar history of thyroid disease, and in
      those which in the physical exploration is not verified goiter neither
      ophthalmopathy.

PMID- 9629772
TI  - [Megestrol in the treatment of AIDS associated cachexia. Evaluation by
      bioelectric impedance analysis of body composition].
AB  - OBJECTIVE: To value the effects of megestrol acetate wer the weight and the body
      composition (fat, lean and body water) in patients with AIDS associated cachexia,
      by bioelectric impedance analysis. SUBJECTS: 25 patients between 23 and 57 years
      of age, with confirmed HIV infection and prior weight lost of 7.96 +/- 4.6 kg in
      relation to their habitual weight in the previous months. All the patients were
      under antiretroviral therapy. METHOD: Basal determination, before the beginning
      of the antianorexic treatment and at the end of it, using bioelectric impedance
      analysis by Maltron BF 905 analyzer, calculating fat, lean and total body water
      in relation to weight, height, age and sex. Oral administration of 320 mg/day
      megestrol acetate for three consecutive months. Statistical comparation (RSIGMA
      and SPSS) by paired t-test of the mean weight, body mass index, fat, lean and
      total body water. RESULTS: During the three months treatment the mean basal body
      weight of the patients increased 3.54 Kg (p < 0.001) at the expense of an
      increase of 2.24 kg in the total body lean (p < 0.01), while the increment of the
      body fat (1.2 kg) was not statistically significant. The total body water
      increased 1.48 L (p < 0.001) and the body mass index in 1.22 kg/m2 (p < 0.001).
      CONCLUSION: Treatment with megestrol acetate results in a substained and very
      significant increase of the weight and body mass index in patients with AIDS
      related cachexia. This increment in weight is at the expense of body lean.

PMID- 9629771
TI  - [Study of the secretion of P substance, neurotensin and somatostatin in healthy
      adults].
AB  - OBJECTIVE: A study in humans of the profile of physiologic secretion, basal and
      postprandial of three gastrointestinal peptides has been carried out. METHOD: 20
      healthy subjects were studied (9 women and 11 men); any previous digestive
      pathology has not been included. The study was carried out by determining P
      substance, neurotensin and somatostatin in plasma by means of RIA I125. The
      subjects were studied in basal conditions of fasting and the samples were taken
      at 30, 60 and 90 minutes intervals after the oral intake of a semi-liquid
      preparation made up of the three immediate principles. RESULTS: It shows the
      secretion curve of the three gastrointestinal peptides, in a global way and also
      in relation to sex, age and body weight.

PMID- 9629773
TI  - [Asymmetric oligoarthritis in Castleman's disease].
AB  - The angiofollicular lymph node hyperplasia (Castleman's disease) is an entity of
      unknown etiology. Its diagnosis is based on clinical and histological criteria.
      We present the case of a 20-year-old male patient with asymmetric oligoarthritis
      and fever which response to nonsteroidal antiinflammatory drugs as onset of
      abdominal Castleman's disease mixed type.

PMID- 9629774
TI  - [Extramedullary anaplastic plasmacytoma].
AB  - A case of extramedullary plasmacytoma of the maxillary sinus, locally aggressive,
      in a 65 years old man is presented. Clinical diagnosis of adenocarcinoma was
      suspected but the pathological study showed an anaplastic morphology, with little
      plasmacytic differentiation and lack of stain with cytokeratins and epithelial
      membrane antigen (EMA), immunohistochemical marker of plasmatic cells, among
      others. Definitive diagnosis was based on light chain restriction and lack of
      multiple myeloma.

PMID- 9629775
TI  - [Presence of Pneumocystis carinii in cerebrospinal fluid].
AB  - Pneumocistis carinii is a ubiquitous protozoan present in mammals which
      frequently causes pulmonary problems in immunodeficient patients, especially
      those infected with the Human Immunodeficiency Virus. Given its particular
      affinity with the lung area, it is rarely present in other tissues. It has on
      occasions been detected in the liver, spleen and lymphatic ganglia, external
      auditory canal, skin and to a lesser extent, other organs. It is extremely rare
      that the pathogen in question produces extra-pulmonary clinical conditions. The
      case presented is that of an ex-intravenous drug user diagnosed as a carrier of
      the HIV/C-3 virus, who presented indications of meningeal pathology and in whose
      cephalorachidian fluid samples were detected Pneumocistis carinii cysts.

PMID- 9629776
TI  - [Amiodarone pulmonary toxicity: radiological coexistence of nodules with
      interstitial and alveolar abnormalities].
AB  - We present a case of amiodarone pulmonary toxicity, special emphasis is given to
      the radiological features because the presence of pulmonary nodules with
      interstitial and alveolar abnormalities. Due to a treatment with amiodarone, the
      patient developed few symptoms, with a low maintenance dose of 200 mg/day.

PMID- 9629777
TI  - [Early biochemical indicators of renal damage in arterial hypertension].
AB  - Hypertensive nephropathy is an important complication of arterial hypertension,
      being a cause of chronic renal insufficiency in a considerable number of
      patients. For years it has been attempted to find an useful marker of nephropathy
      in the incipient phases of the disease. We revised the main biochemical
      indicators of renal damage, paying special attention to hyperuricemia,
      microalbuminuria, and urinary excretion of beta-2-microglobulin and N-acetyl-beta
      glucosaminidase. Each one of them expresses alterations in the glomerular
      filtrate, lesion of capillary endothelium or anomalies of the tubular function.
      None of them demonstrated to be specific to nephroangiosclerosis, but they guide
      us on the structural and functional alterations occurring in the first stages of
      hypertensive nephropathy.

PMID- 9629779
TI  - [Rounded atelectasis and abnormally positioned heart].

PMID- 9629778
TI  - [Silicone and autoimmune diseases].
AB  - There exists controversy surrounding the potential relationship between silicone
      implants and autoimmune diseases. Indeed, silicone is not an inert substance and
      microparticles from the prosthesis can migrate causing localised or generalised
      reactions. Most notably, silicone has been associated with sclerodermia and human
      adjuvant disease. Sclerodermia has been observed within 50% patients suffering
      from autoimmune diseases linked with silicone. For patients with symptoms, the
      removal of the prosthesis achieves a favourable response in 50% of the cases.
      Before a patient undergoes a silicone implant, it is essential that personal and
      family history of autoimmune disorders are ascertained and evaluated. Also, the
      patient should undergo regular check ups after having received the implant. In
      spite of the fact that certain epidemiological studies have not demonstrated a
      relationship between silicone implants and autoimmune disease, the continual
      appearance of new cases means that the physician should have an open attitude and
      be aware of the possibility.

PMID- 9629780
TI  - [Chronic eosinophilic pneumonia].

PMID- 9629781
TI  - [Hyporeninemic hypoaldosteronism: a new manifestation of POEMS syndrome?
      Description of a case].

PMID- 9629782
TI  - [About the language of our patients].

PMID- 9629783
TI  - [Bronchiolitis obliterans organizing pneumonia, biochemical cholestasis and late
      development of rheumatoid arthritis].

PMID- 9629784
TI  - [Composition of master formulas for the treatment of obesity].

PMID- 9629785
TI  - [Traveler's phlebitis].

PMID- 9629786
TI  - [Diagnostic imaging of intrahepatic lesions].

PMID- 9629787
TI  - [Treatment of acute otitis media. Old pathogens, new trends].

PMID- 9629788
TI  - [Molecular pathology of osteochondrodysplasias].

PMID- 9629789
TI  - [Protocols and basic clinical norms to follow in order to obtain the certificate
      of eradication of poliomyelitis in Spanish territory].

PMID- 9629790
TI  - [Vaccination against Haemophilus influenzae type b in the Valencia Community:
      efficacy and failure of vaccinations].
AB  - OBJECTIVE: To study Haemophilus influenzae type b (Hib) conjugate vaccine
      effectivity and vaccine failures in the Valencian Community of Spain where
      vaccine can be obtained, but is not scheduled as a routine immunization. PATIENTS
      AND METHODS: A prospective surveillance system where pediatricians and
      microbiologists of all public hospitals of the Valencian Community reported cases
      of invasive Hib disease in children (under 15 years of age). Vaccination status
      (number of doses, dates and type of vaccine) in each case was obtained. RESULTS:
      Of 23 cases reported from December 1, 1995 to November 30, 1996, two had received
      at least one dose of Hib vaccine. One was a true vaccine failure and the other an
      apparent vaccine failure. Estimating a vaccine coverage of 32.5% of the children
      less than 5 years old, the direct vaccine effectivity was 90.6% (IC 95%: 27.9
      98.8%). CONCLUSIONS: Hib conjugate vaccine is effective in the Valencian
      Community, however, there is still invasive disease due to the low vaccine
      coverage and some vaccine failures.

PMID- 9629791
TI  - [Biochemical, enzymatic and genetic study of hypoxanthine guanine phosphoribosyl
      transferase (HPRT) deficiency].
AB  - OBJECTIVE: The objective of this study was to analyze the diagnosis of HPRT
      deficiency, perform a thorough purine metabolism study and to establish the
      carrier and prenatal diagnosis in 16 HPRT deficient families. PATIENTS AND
      METHODS: Plasma and urinary concentrations of uric acid, creatinine and
      oxypurines, APRT and HPRT activities in hemolysates and HPRT in intact
      erythrocytes and adenine 8-C14 urinary excretion were analyzed. Carrier diagnosis
      was made by hair root enzyme analysis and genetic studies. RESULTS: These studies
      allowed the diagnosis of HPRT deficiency in 20 patients. Carrier diagnosis could
      be performed in 23 women at risk and in a 9 week old female fetus. CONCLUSIONS:
      The study results suggest that HPRT deficiency accounts for increased purine
      nucleotide degradation. This increase results in elevated urinary and plasma
      concentrations of hypoxanthine, xanthine and uric acid. The clinical severity of
      the disease is not related to the degree of urinary or plasma concentrations of
      oxypurines. Hair root analysis generally allows the diagnosis of carrier status,
      but the carrier state cannot be fully excluded in women at risk. When the
      familial mutation causing the defect in HPRT is known, analysis of the
      differences in the restriction pattern of the HPRT gene (natural or due to
      directed mutagenesis) allow a rapid and reliable diagnosis of carrier status and
      HPRT deficiency.

PMID- 9629792
TI  - [Urethrocystography in children. Practical considerations of irradiation doses].
AB  - OBJECTIVE: Rational use of voiding cystourethrography (VCUG) is imperative, as it
      is an invasive procedure exposing the child to ionizing radiation and other well
      documented risks. The objective of this study was to contribute to the
      achievement of a reduction in the irradiation dose in VCUG. PATIENTS AND METHODS:
      We reviewed the medical records of a consecutive sample of 125 children that
      underwent VCUG in our hospital between January 1995 and June 1996. RESULTS: Of
      the 125 VCUGs, 100 were normal, 13 showed vesicoureteric reflux grade II or
      higher, and 12 of them presented with other anomalies. The indication for VCUG
      was febrile UTI in 54 children, hydronephrosis detected prenatally in 12 and
      other causes in 60 children. It is important to note that children with
      vesicoureteric reflux presented as febrile UTI or fetal hydronephrosis. The age
      was significantly lower in the reflux group (p < 0.01). Eleven of the 13 children
      with vesicoureteric reflux were less than one year of age. Ultrasound anomalies
      and renal scarring in Tc99 DMSA were seen in a larger proportion in the reflux
      group. Preliminary X-rays showed anomalies in only 3 of 125 cases. CONCLUSIONS:
      1) Vesicoureteric reflux is related to febrile UTI and fetal hydronephrosis. The
      other indications are questionable. 2) VCGU is not recommended following the
      first UTI in the evaluation of children 6 years of age or older who have a normal
      ultrasound and Tc99 DMSA. 3) VCUG could be substituted by a nuclear cystogram in
      girls who do not have a history of voiding dysfunction. 4) A preliminary X-ray is
      not justified.

PMID- 9629793
TI  - [Complications of cerebrospinal fluid shunt].
AB  - OBJECTIVE: The objective of this study was to know the incidence, mode of
      presentation, clinical and microbiological aspects, as well as the management of
      ventriculo-peritoneal shunt malfunction. PATIENTS AND METHODS: A retrospective
      study was carried out where thirty-seven children with malfunctioning shunts were
      studied. The mechanical causes of shunt malfunction included disconnection,
      fracture and obstruction, while infection was considered as either a clinical or
      analytical change (blood and/or CSF). RESULTS: The mean age of the patients was
      5.5 years. The most common indication for the insertion of the
      ventriculoperitoneal shunt was congenital hydrocephalus. The average stay in the
      ICU was 8.2 days. Mechanical dysfunction was detected in 25 patients (68%) and
      infectious etiology in 12. The most common clinical manifestations were vomiting,
      fever and headache. CSF biochemical alteration was found in 8 of the infected
      group. Staphylococcus was isolated in six of the 8 cases. The
      ventriculoperitoneal shunt was changed during the first 24 hours in 17 of 25
      patients (68%) with mechanical malfunction, while 11 cases with an infective
      cause (92%) were managed with an external shunt. The interval between the
      insertion of the ventriculoperitoneal shunt and the malfunction was over 6 months
      in 20 cases (54%). CONCLUSIONS: Ventriculoperitoneal shunts are the main method
      for treating hydrocephaly, although they are not without complications which may
      require surgical procedures. Appropriate surgical technique, asepsis, as well as
      prophylactic antibiotics are essential to decrease the incidence of
      complications.

PMID- 9629794
TI  - [Effect of nucleotides as dietary supplement on diarrhea in healthy infants].
AB  - OBJECTIVE: The objective of this study was to evaluate the effect of nucleotide
      supplements on the incidence, duration and severity of diarrhea in healthy
      infants. PATIENTS AND METHODS: A total of 3,243 cases were studied. This was an
      observational cohort study with a 1:1 ratio between infants receiving a
      nucleotide supplemented/unsupplemented diet. From the start of the study until
      the infant reached 6 months of age, the infant's mother recorded the duration and
      severity of each episode of diarrhea. The infant's height and weight were
      measured at the beginning and at the end of the follow-up period and the
      nutritional index (NI) was calculated [NI = (actual weight/actual height)/(ideal
      weight/ideal height)/100]. Data collection was performed during the months of
      June through December 1996 at 340 pediatric clinics distributed throughout Spain.
      RESULTS: The study groups were found to be homogeneous and there were no
      significant differences in age, gender, duration of follow-up, referring
      pediatric offices, number of siblings, usual residence, habitat or nursery
      attendance. The incidence of diarrhea was significantly lower (p < 0.001) in the
      nucleotide supplemented group (11.1%) versus the unsupplemented group (17.4%).
      Similarly, both the maximum duration of diarrhea (p < 0.05) and the severity of
      episodes of diarrhea (p < 0.001) were significantly lower in the nucleotide
      supplemented group. No significant differences were found between the initial and
      final nutritional indexes within a group nor when comparing the two groups.
      CONCLUSIONS: Nucleotide supplemented starter formulas reduce the incidence,
      duration and severity of diarrhea in healthy infants, but weight and height were
      not affected.

PMID- 9629795
TI  - [The value of C-reactive protein in the diagnosis of acute appendicitis in
      children].
AB  - OBJECTIVE: The aim of this study was to evaluate the usefulness of C-reactive
      protein values in the diagnosis of acute appendicitis, either as a single test or
      in combination with total white cell count. PATIENTS AND METHODS: Two hundred and
      thirty-one children with suspected appendicitis were analyzed. C-reactive protein
      and total white cell counts were measured and compared with the duration of
      symptoms and histological diagnosis. Both tests were compared by receiver
      operating characteristic curves and the probability for the use of both tests
      together was calculated. RESULTS: Ninety out of 231 patients had abdominal pain
      that did not demand surgery. One hundred and forty-one children had
      histologically confirmed appendicitis (subgroups: 101 acute, 25 gangrenous and 15
      perforated appendices). Mean C-reactive protein levels at admission were 25.1, 55
      and 66.7 mg/L, respectively in these histological subgroups and 14.9 mg/L in the
      non-appendicitis group (p < 0.001). The total white cell count was also
      statistically significant. Both tests were equally valuable in patients whose
      symptoms had a duration of more than 12 hours. The total white cell count was
      more valuable in patients with less than 12 hours of symptoms. The likelihood
      ratio for appendicitis was 2.72 for a C-reactive protein greater than 20 mg/l and
      a total white cell count above 15,000/mm3. The likelihood ratio of not having
      appendicitis was 0.37 when both tests were below these values. CONCLUSIONS:
      Measurement of C-reactive protein is useful in the diagnosis of acute
      appendicitis, mainly in cases with more than 12 hours of evolution. The combined
      tests improved the predictive values.

PMID- 9629796
TI  - [Musculoskeletal pain in pediatric patients. Prevalence and etiology in Primary
      Care].
AB  - OBJECTIVE: 1) To determine the number of clinic visits in primary care due to
      musculoskeletal pain in children > or = 3 years. 2) To describe the demographic
      characteristics of the population assessed for limb/back pain. 3) To characterize
      the etiology of musculoskeletal pain in a general pediatric clinic. PATIENTS AND
      METHODS: A prospective lineal study was performed between October 30, 1996 and
      January 14, 1997 in two urban general pediatric clinics located in the city of
      Madrid (Spain). During the period of the study, all consultations related to
      musculoskeletal pain were registered in a protocol form. In addition, a registry
      of all clinic visits was maintained during the study. RESULTS: During the study
      period, 43 clinic visits were due to musculoskeletal pain, representing 6.2%
      (43/692) of the clinic visits in children > or = 3 years of age (95% confidence
      interval 4.4-7.9%). The mean age was 9.8 years (+/- 3.2 years). These complaints,
      although statistically non-significant, were more frequent in children > or = 10
      years old (53.4%) and in males (65.1%). The most frequent complaints were knee
      athralgias (30%), arthralgias of other joints (23%) and soft tissue pain (18%).
      These symptoms were usually due to overuse syndromes and normal skeletal growth
      variants. CONCLUSIONS: The increase of primary pediatric care age from 7 to 14
      years of age is associated with an increase in the number of consultations
      related to musculoskeletal pain. This information should be kept in mind at the
      time of designing continuing medical education and training programs in
      pediatrics.

PMID- 9629797
TI  - [Treatment of cardiac arrhythmia with radiofrequency in pediatrics].
AB  - OBJECTIVE: The use of radiofrequency ablation of cardiac arrhythmias in
      pediatrics requires demonstration that the technique is effective and devoid of
      significant complications. In this study we present our experience in the
      ablation of cardiac arrhythmias in children and adolescents. PATIENTS AND
      METHODS: Between January 1992 and January 1997 we performed a total of 1,543
      radiofrequency ablation procedures. Of these, 130 were performed in 117 patients
      younger than 18 years of age (58 were younger than 14 years old). Indication for
      ablation was the presence of drug refractory recurrent paroxysmal
      supraventricular tachycardia in 112 patients and permanent ventricular
      preexcitation in 5 asymptomatic patients. Final diagnosis in the 112 symptomatic
      patients was: 4 atrial tachycardias, 21 atrio-ventricular nodal reentrant
      tachycardias, 53 Wolff-Parkinson-White (WPW) syndromes, 33 orthodromic
      tachycardias using a concealed accessory pathway and 1 idiopathic left
      ventricular tachycardia. RESULTS: The initial ablation procedure was effective in
      109/117 patients (93%) with a total duration of 90 +/- 31 minutes, using 16 +/-
      11 minutes of radioscopy and a median of 4 radiofrequency applications. During
      follow-up, recurrence occurred in 9 patients (8%). In 7 of them and in 6 of those
      with an unsuccessful initial procedure, a second effective procedure was
      performed in 11/13 patients. Finally, radiofrequency ablation was effective in
      111/117 patients (95%). We observed a single complication in a 15 year old girl
      who presented a thrombosis of the right femoral artery requiring balloon
      recanalization. Comparison of these results with those in the adult population
      showed no difference in terms of effectiveness, recurrences or complications.
      CONCLUSIONS: Radiofrequency ablation of cardiac arrhythmias in pediatric and
      young patients can be safely and effectively done. Results are similar to those
      obtained in adults suggesting that indications for ablation can also be similar.

PMID- 9629798
TI  - [Effect of hyperbilirubinemia on biologic rhythms in healthy full-term neonates].
AB  - OBJECTIVE: The toxicity of bilirubin (BP) on the brain presents unknown aspects.
      Therefore, the treatment for neonatal hyperbilirubinemia is controversial. The
      aim of this study was to establish if moderate levels of BP produce toxicity in
      brain nuclei that regulate the biological rhythms (BR) of healthy full-term
      newborns. PATIENTS AND METHODS: We studied 17 jaundiced (BP 12.8-18.1 mg/dl) and
      36 non jaundiced newborns. Heart and respiratory rate, temperature and systolic
      blood pressure were recorded during 24 hours at 30 minute intervals. Cosinor
      analysis was used to calculate the incidence of BR. The Fisher exact test was
      carried out to compare both groups and the relative risks to determine the
      association between hyperbilirubinemia and the absence of BR. RESULTS:
      Differences in the BR parameters did not reach statistical significance.
      Differences in heart rate 12-h BR (p = 0.071) and systolic blood pressure 8-h BR
      (p = 0.076) approached a statistical significance. The 95% confidence intervals
      of the relative risks were all close to 1 and the lower limits in respiratory
      rate (0.40) and systolic blood pressure (0.35) 24-h BR indicate a negative
      association. CONCLUSIONS: The aim was to verify the relationship between moderate
      neonatal hyperbilirubinemia and the decrease in the incidence of BR. The results
      do not show the sought after relationship and provide evidence against
      neurotoxicity from moderate levels of bilirubin. The limited evidence for
      developing long term mental alterations permits us to make an optimistic
      prognosis for full-term newborns with moderately elevated levels of bilirubin.

PMID- 9629799
TI  - [Analysis of the risk of congenital defects in different ethnic groups in Spain].
AB  - OBJECTIVE: The frequency of congenital defects is not the same in different
      populations and ethnic groups. Genetic factors, as well as differences in socio
      cultural aspects (such as the frequency of consanguineous couples) between the
      groups could be responsible for some differences in the prevalence of congenital
      anomalies. However, some groups are made up of populations which live on the
      fringe of society in which several circumstances and related factors could
      increase the risk for congenital defects. PATIENTS AND METHODS: A total of 24,696
      malformed infants were studied together with a similar group of controls,
      separated into the following ethnic groups: Gypsies, black, orientals, Arabic
      people and whites. Using different models of logistic regression analysis,
      controlling several factors related to the social-cultural level and with genetic
      aspects (such as consanguinity), we estimated the risk for 20 different
      congenital defects in the ethnic groups compared to the white population.
      RESULTS: The analysis showed that some ethnic groups have an increased risk for
      some congenital defects and that this increased risk is due to their high level
      of consanguinity. Other defects are due to different factors related with the low
      socio-cultural level. However, in black and Arabic people there is a high risk
      for some congenital defects that is not attributable to those genetic or socio
      cultural factors studied. CONCLUSIONS: The results of the present study permit
      the estimation of the impact of congenital defects in these groups that have low
      socio-cultural level, as well as the need for health care. This is of great
      usefulness in establishing the necessary actions to provide proper assistance to
      prevent congenital defects in these populations.

PMID- 9629801
TI  - [Sexual precocity in a 7-year old girl, due to a tumor of the ovarian sex cord
      with annular tubules (SCTAT of Scully)].

PMID- 9629800
TI  - [Neonatal sepsis: epidemiologic indicators and relation to birth weight and
      length of hospitalization time].
AB  - OBJECTIVE: All cases of neonatal septicemia among neonates admitted to the
      neonatal unit in the pediatric department (CHUS) in Santiago de Compostela
      between 1992 and 1995 were studied. Our aims were: 1) To assess the incidence and
      microbial epidemiology. 2) To study the incidence of coagulase-negative
      staphylococci (CONS) sepsis stratified according to birth weight and gestational
      age. 3) To assess the incidence density of sepsis (IDS) and 4) To analyze the
      associated mortality. PATIENTS AND METHODS: One hundred eighteen episodes of
      sepsis in 103 neonates which fulfilled clinical and laboratory criteria with
      positive blood cultures were included in this study. Between the years of 1992
      and 1995 there were 318 neonates suspect of having sepsis among the 2,083 who
      were admitted to the unit during this period and which came from our own
      maternity department, as well as other centers. RESULTS: In this period there
      were 10,457 live births in our maternity department. The annual incidence of
      sepsis was 6/1000 live births. Early onset sepsis was observed in 2.5/1000 live
      births (26 cases) and the occurrence of late onset increased to 3.5/1000 live
      births (36 cases). Neonatal sepsis was confirmed in 103 neonates (4.9%)
      corresponding to 118 episodes of sepsis. S. epidermidis was the most frequent
      agent isolated in blood cultures (38.1%). The highest incidence of sepsis caused
      by S. epidermidis was observed in neonates below 1500 g (12.1%) and less than 32
      weeks gestational age (13.4%). The incidence was lower in those whose birth
      weights were more than 2500 g (1.9%) and > 37 weeks of gestational age (1.6%), p
      < 0.001. Overall mortality due to sepsis was 0.7% and increased to 5.0% among
      hospitalized newborns with birth weights below 1500 g. The average IDS stratified
      in three groups of birth weight and gestational age was 18 sepsis work-ups per
      1000 patient-days of hospitalization, the lowest IDS 12.9/1000 was found in
      neonates whose birth weights were between 1501 g and 2500 g in comparison with
      neonates who weighted more than 2500 g (21.5/1000), p < 0.05, and very similar to
      the IDS found in the intermediate group of gestational age (13.1/1000).
      CONCLUSIONS: S. epidermidis and other CONS are the main agents causing sepsis in
      hospitalized neonates, although there is a decreasing trend of incidence (-71.1%)
      between the years 1992 and 1995 (5.0% vs 1.5%). Gram-negative organisms and S.
      agalactiae played a minor role as agents causing sepsis even though S. agalactiae
      is the most important agent in early onset sepsis. Overall mortality associated
      with sepsis (7/1000 live births) is in or under the average range of
      international statistics. Indexes of IDS are more valuable as epidemiological
      tools in assessing septicemia than the simple attack rate because they have taken
      into consideration the length of stay, number of hospitalized newborns, as well
      as the number of positive sepsis work-ups in the calculating process.

PMID- 9629802
TI  - [Terminal 22q deletion: report of a case and review of the literature].

PMID- 9629803
TI  - [Suppurative parotitis in the neonatal period. Report of two cases and review of
      the literature].

PMID- 9629804
TI  - [Manifestations of congenital leukemia as non-immunologic hydrops fetalis].

PMID- 9629805
TI  - [Cardiac manifestations of AIDS in pediatric patients].

PMID- 9629806
TI  - [Ramsay-Hunt syndrome in infancy. Apropos of a case].

PMID- 9629807
TI  - [What is your diagnosis? Torticollis in infancy].

PMID- 9629808
TI  - [Acute pain, analgesia and sedation in children (IIIa): pharmacokinetics amd
      pharmacodynamics of analgesic opioids].

PMID- 9629809
TI  - [Rotavirus: vaccines].

PMID- 9629810
TI  - Emerging opportunities to fight breast cancer.

PMID- 9629811
TI  - Screening for colorectal cancer--the AHTAC report: where do we go from here?

PMID- 9629812
TI  - Promoting the health of Australians--how strong is our infrastructure support?

PMID- 9629813
TI  - Data for diagnosis, monitoring and treatment in indigenous health: the case of
      cervical cancer.
AB  - Deficiencies in the availability and quality of data on the health status of
      indigenous Australians have long been recognised. For cervical cancer, data
      demonstrate a 2-5 fold greater incidence rate and an 8-10 fold greater mortality
      rate for Indigenous women compared to non-Indigenous Australians. However,
      incidence and mortality data are only available for some states and there is
      little or no information available on the geographic or social distribution of
      risk, or the reasons for risk differentials. There are also little or no data on
      the utilisation of, or preferences for, screening services. Thus, while there is
      clearly a need for a cervical cancer control program specifically to target
      Indigenous women, current data are inadequate to inform planning and
      implementation, and current systems are inadequate to monitor effectiveness. This
      situation is the result of insufficient research and inadequate attention to
      recording of Indigenous status in routine data systems and applies to a greater
      or lesser extent across the spectrum of health of Indigenous Australians. Health
      workers across the spectrum in mainstream and Indigenous medical services have a
      shared responsibility for improving the availability and quality of data and
      ensuring the appropriate use of information necessary to achieve and monitor
      improvements in service delivery and health status of Indigenous people.

PMID- 9629814
TI  - Cervical cancer screening in rural NSW: Health Insurance Commission data compared
      to self-report.
AB  - There are several sources of data for estimates of community Pap test rates,
      including self-report, pathology laboratory records and Health Insurance
      Commission (HIC) data. Estimates of screening rates can vary considerably
      according to the sampling frame and data source. This study aimed to compare the
      self-reported estimates of cervical cancer screening with HIC estimates for women
      in rural NSW towns. Self-report of a Pap test in the past two years from 2,498
      women in 19 rural towns of NSW was compared to HIC-provided Pap test rates. Self
      report levels were adjusted for non-HIC providers and HIC levels included data
      from the Victorian Cytology Register. Self-report estimates were significantly
      higher than HIC estimates in 18 of the 19 towns, with discrepancies ranging from
      13% to 29%. HIC-recorded providers accounted for between 65% and 100% of Pap
      tests per town, according to self-report. The highest Pap test rate by self
      report was 70.1%, the highest by HIC was 49.2%. The lowest Pap test rate by self
      report was 45.2%, the lowest by HIC was 26.1%. There was significant variation in
      Pap test rates between towns for adjusted self-report estimates, but not for the
      crude self-report estimates. Researchers should always be aware of both the
      possible variations according to data source and the inherent biases for
      whichever data source is used. An extra caution is given to consider the
      public/private provider profile when exploring possible geographical differences
      in Pap test rates.

PMID- 9629815
TI  - Effects of a smoking cessation program for pregnant women and their partners
      attending a public hospital antenatal clinic.
AB  - This study aimed to assess the effect of a hospital-based smoking cessation
      intervention delivered by midwives during routine antenatal and postnatal care on
      the smoking habits of pregnant women and their partners. At the first antenatal
      visit, women in the intervention group (n = 110) were given a demonstration of
      the immediate effects of smoking on foetal heart rate, brief smoking cessation
      advice and smoking cessation booklets for themselves and their partners; at
      delivery, they were given brief advice and a booklet about postpartum cessation.
      Compared with an historical control group who received usual care (n = 110) and
      assuming those lost to follow-up continued to smoke, biochemically-verified
      maternal cessation sustained from at least 24 weeks gestation to late pregnancy
      was 6.4% in the intervention group and 1.8% in the comparison group. However,
      there was no difference between maternal quit rates at six months postpartum.
      Partners were more likely to try to quit in the intervention group, but quit
      rates did not differ. Exposure to the intervention was not associated with
      increased levels of psychological distress, as measured by the 12-item General
      Health Questionnaire. We conclude that this type of intervention, when
      implemented by staff during routine care, is probably associated with a small
      improvement in maternal cessation in pregnancy, similar to that produced by
      minimal advice to quit smoking.

PMID- 9629816
TI  - Smoking by adolescents: three years later, there's even larger revenue but little
      for prevention.
AB  - This research aimed to determine whether, between 1990 and 1993, there were any
      changes in the government revenue gained from sale of cigarettes to minors and
      the proportion of this revenue spent on attempting to prevent the uptake of this
      habit by adolescents. The methodology is consistent with the 1990 study, although
      some revisions have been necessary. From our analysis, it is estimated that state
      revenue from under-age smoking increased 97% from $9.37 million in 1990 to $18.45
      million in 1993. State expenditure on anti-smoking campaigns (for the entire
      population) increased 24% from $9.47 million in 1990 to an estimated $11.75
      million in 1993. When this expenditure is converted to a relative amount,
      relative state expenditure per under-age smoker fell an estimated 10%, from $4.40
      in 1990 to $3.98 in 1993. This is equivalent to approximately 7.7% and 5.1%, in
      1990 and 1993 respectively, of state revenue from cigarette smoking by those
      under the legal purchase age being spent on discouraging adolescents from taking
      up this habit. These results suggest a growing inequity in the expenditure on
      anti-smoking activities compared to revenues received from sales to minors.

PMID- 9629817
TI  - Screening for unhealthy lifestyle factors in the workplace.
AB  - OBJECTIVE: To examine (1) the prevalence of four lifestyle behaviours among
      Australia Post employees and (2) employees' perceptions of the role of the
      workplace in promotion of lifestyle change. DESIGN: A cross-sectional survey
      using a self-administered questionnaire involved 688 employees working in
      Australia Post throughout metropolitan Sydney. MAIN OUTCOME MEASURES: Prevalence
      related to age and sex of alcohol consumption, cigarette smoking, inadequate
      exercise, perception of excessive weight. RESULTS: 36% of men and 11% of women
      reported drinking alcohol at levels considered hazardous or harmful; 33% of men
      and 25% of women reported smoking; 51% of men and 62% of women thought they were
      overweight; 30% of men and 39% of women did not exercise regularly. Younger
      respondents were more likely to report drinking hazardously or harmfully, were
      smokers and had multiple risk factors. A majority of respondents thought that
      their employer should be interested in employee's lifestyle issues, particularly
      excessive drinking (63%). However, few considered seeking advice from the
      workplace regarding smoking (16%), weight (25%) and excessive alcohol consumption
      (12%). CONCLUSIONS: These results show that many of Australia Post employees have
      unhealthy lifestyle behaviours. While employees perceive that the workplace has
      an important role in promoting healthy lifestyles among staff, few are presently
      willing to seek advice from the workplace regarding these issues. Promotion of
      healthy lifestyles in Australian workplaces is a potentially important public
      health advance that could reduce the incidence of diseases associated with high
      risk lifestyle behaviours.

PMID- 9629818
TI  - Can non-prosecutory enforcement of public health legislation reduce smoking among
      high school students?
AB  - BACKGROUND: Smoking by adolescents has been identified as a major public health
      issue. Raising the legal age of cigarette purchase from 16 to 18 years has
      attempted to address the issue by restricting adolescents' access.
      METHODS/STRATEGY: A prospective study evaluating the impact of non-prosecutory
      enforcement of public health legislation involving 'beat police' was conducted in
      the Northern Sydney Health region. Secondary students, aged 12 to 17 years, from
      both intervention and control regions were surveyed about cigarette smoking
      habits by means of a self-completed questionnaire administered pre- and post
      intervention. RESULTS: 12,502 anonymous questionnaires were completed. At
      baseline, 19.3% of male students and 21.2% of female students indicated they were
      current smokers. Age and sex stratified chi-squared analysis revealed
      significantly lower post-intervention smoking prevalence for year 8 and 10
      females and year 7 males among the intervention group. Higher post-intervention
      smoking prevalences were demonstrated for year 7 and 9 females and year 8 males
      among the intervention group and in year 10 males and year 11 females among the
      control group. The analysis of combined baseline and follow-up data from
      coeducational schools with logistic regression techniques demonstrated that the
      intervention had a significant effect in reducing smoking prevalence among year 7
      students only (OR = 0.54). CONCLUSION: Our study demonstrates the difficulties in
      restricting high school students' access to cigarettes. Isolated non-prosecutory
      strategies are likely to only have a limited impact on reducing smoking
      prevalence among high school students.

PMID- 9629819
TI  - Impact in general practice of the policies of the organised approach to
      preventing cancer of the cervix.
AB  - This cross-sectional survey of cancer screening in May 1996 used a national
      random sample of a specified group of general practitioners (GPs). The survey
      included items to assess the impact of the Organised Approach to the Prevention
      of Cervical Cancer (OAPCC). Of the 1,271 GPs who satisfied the eligibility
      criteria, 855 (67%) returned a completed questionnaire. Fifty-two per cent
      indicated they would be 'highly' likely to introduce a discussion about cervical
      smears to a 58-year-old woman who was in good health and had come for a non
      gynaecological consultation. Female sex, RACGP affiliation, practising in a
      metropolitan area and awareness of the OAPCC booklet were independent predictors
      of an opportunistic orientation. By contrast, 91% indicated that they would be
      'highly' likely to include a Pap smear in a general health checkup. Thirty-eight
      per cent reported that they had found the booklet about the 1991 screening policy
      'very' useful, while 38% found the NHMRC guidelines for the management of women
      with screen detected abnormalities 'very' useful. Around one-fifth of the GPs
      were not aware of these documents. Overall, 19% still recommended annual or more
      frequent screening. GPs from NSW and Queensland were less likely to support
      biennial screening than GPs from other states. Overall, 26% of GPs did not
      indicate that they would refer a woman who had tested positive for any grade of
      CIN for colposcopic assessment. Female GPs were more likely to refer women with
      CIN for colposcopic assessment while older doctors were less likely to do so.

PMID- 9629820
TI  - Cancer incidence and mortality around a hazardous waste depot.
AB  - The Castlereagh Regional Waste Disposal Depot (CRWDD) has been the focus of
      community concerns regarding the impact of hazardous waste disposal on their
      health and that of their local environment. As part of a phased epidemiological
      approach to investigate the levels of illness in people living in the vicinity of
      the CRWDD, routinely collected data were used to determine the rates of cancer
      and mortality in the area around the site and whether these rates were higher
      than expected when compared with New South Wales (NSW). The area investigated was
      based on eight census collection districts around the boundary of the CRWDD.
      Cancer incidence and mortality in the study area were calculated and compared to
      NSW using the indirect method of age and sex standardisation. Over an 18-year
      period, brain cancer in males (six cases) was the only cancer where the incidence
      in the study area was significantly higher than expected (SIR 380, 95% CL 139.4,
      826.6). When this data were examined over smaller (arbitrary) time periods, there
      was an apparent cluster of brain cancer in males (three cases) between 1989 and
      1991 (SIR 905, 95% CL 187,2646). There was a significant concentration of cases
      of cancers of the breast in females and cancers of the uterus over the smaller
      time periods. Although continued surveillance of these cancers is recommended,
      there are several basic limitations associated with small area data analysis that
      prevent a clear interpretation of these results. This limits our ability
      categorically to resolve the concerns of those living in the vicinity of the
      CRWDD.

PMID- 9629821
TI  - The short-term financial costs of abnormal Pap smears to women and government in
      Australia.
AB  - Using data collected from a private Canberra colposcopy service, we examined the
      direct costs, to women and government, of the gynaecological care of women with
      cervical cytological abnormalities and determine the potential savings of
      implementing the Commonwealth recommendations for the clinical care of women with
      screen-detected abnormalities. We performed a case note audit of 502 women who
      first attended a gynaecologist because of an abnormal Pap smear between 1 January
      1989 and 30 April 1990. The smear resulting in their referral--their presenting
      smear--was categorised as No CIN (showing no evidence of cervical intraepithelial
      neoplasia), CIN 1, CIN 2 and CIN 3. The average costs to government (p for trend
      < 0.001) and women (p for trend = 0.006) increase as the presenting smear
      increases in severity; the median costs to government (p for trend < 0.001) and
      women (p for trend < 0.001) also rose with increasing cytological severity.
      Treatment of CIN 1 and No CIN accounted for half the costs incurred by government
      and women. Although costs increase with increasing severity of cytological
      abnormality, adherence to new Australian guidelines for the gynaecological care
      of women with screen-detected cervical abnormalities could result in substantial
      short-term savings to government and women.

PMID- 9629822
TI  - Exploring the possibility of sexual-behavioural primary prevention interventions
      for cervical cancer.
AB  - Consistent causal and risk factors for cervical cancer indicate that primary
      prevention may be beneficial for cervical cancer prevention. However, social or
      behavioural primary prevention strategies are seldom discussed in the prevention
      literature. This paper uses thematic analyses of interviews with key informants
      involved with cervical cancer prevention policy development in New Zealand to
      explore the possibility of sexual-behavioural primary prevention. While many
      informants perceived primary prevention to be important, others were cautiously
      accepting or opposed to it. Many concerns were raised that highlighting a
      preventable (sexually transmitted) causal factor might lead to blame and stigma
      around cervical cancer and reduce participation in cervical screening. Much of
      the support for primary prevention depended on it being conducted (indirectly) in
      the context of young people's sexual health education. Positions on primary
      prevention appeared to be informed by common presumptions about what happens in
      the 'real world' and the commonality of human papilloma virus in the general
      population. We contend that the possible health benefits from sexual-behavioural
      strategies for cervical cancer primary prevention need further exploration.

PMID- 9629823
TI  - Childhood incidence of acute lymphoblastic leukaemia and exposure to broadcast
      radiation in Sydney--a second look.
AB  - INTRODUCTION: Recent findings of an apparent association between incidence of
      childhood leukaemia and radio frequency radiation (RFR) from television
      transmission antennas in Sydney, NSW, are examined. METHODS: Incidence of
      childhood (0-14 years) acute lymphoblastic leukaemia (ALL) at the local
      government area (LGA) level is related to estimated exposure levels of RFR from
      television transmission antennas, using Poisson regression techniques. RESULTS:
      Most of the association between ALL incidence and television transmission RFR is
      shown to be the result of an influential observation: one of the highly exposed
      LGAs contributes all the excess, while in a similarly exposed LGA childhood ALL
      incidence was found to be no higher than the rate expected for NSW. With the
      influential observation excluded from the analysis, no positive correlation
      between exposure to RFR and leukaemia is evident. Conversely, under the
      assumption of an association with RFR, the low probability of the observed
      incident cases in LGAs under conditions of relatively high exposure to RFR
      conflicts with the assumption of an effect. CONCLUSION: The apparent association
      between childhood ALL incidence and RFR radiation from television towers is
      weaker when an LGA-level analysis is conducted.

PMID- 9629824
TI  - Older men's concerns about their urological health: a qualitative study.
AB  - While there has been widespread recent interest in men's health issues, and
      prostate cancer in particular, there have been few studies to determine which
      issues are important from the viewpoint of men themselves. This study was
      undertaken to identify genitourinary issues of concern to older men. A series of
      19 focus groups involved 137 men and 14 women from a broad demographic
      background. Men expressed consistent concern about urinary symptoms, prostate
      cancer and sexual function. They revealed misunderstanding and a desire for more
      information about all issues. Urinary symptoms had a high impact on quality of
      life that could be made worse by environmental constraints such as working
      conditions and availability of toilets. Prostate cancer was a concern in all
      groups, even those at low risk, and men believed that screening for prostate
      cancer should be offered. Men believed sexuality was not recognised as an issue
      of concern to older people. Potential barriers to health action included
      stoicism, not talking about health issues and poor relationships with doctors.
      The study suggests a substantial need for community and professional education
      and for health promotion focused on preventable morbidity.

PMID- 9629825
TI  - Australian general practitioners' views and use of tests to detect early prostate
      cancer.
AB  - To describe general practitioners' current beliefs, knowledge and self-reported
      practices in prostate cancer screening, we conducted a national survey of 1,271
      general practitioners, obtaining 855 completed questionnaires (67% response
      rate). Available tests for prostate cancer screening, namely DRE and PSA alone
      and in combination, were indicated to be effective by 49%, 43% and 68% of
      respondents respectively, with older GPs significantly more likely to hold these
      views. The effect of guidelines was mixed. Less than 8% of respondents indicated
      they did not recommend screening. Although the majority of GPs were unlikely to
      adopt an opportunistic approach to prostate cancer screening, 63%, 57% and 46%
      indicated they would recommend DRE, PSA or both respectively during a dedicated
      health check up. Awareness of relevant guidelines was low, with nearly half of
      respondents unable to recall publications from the RACGP or ACS. Counter
      intuitively, awareness of ACS guidelines for prostate cancer screening (which
      advise against screening) was significantly associated with the converse
      behaviour. Findings from this first national study behove proactive and highly
      targeted dissemination in general practice of the AHTAC policy announced by the
      Commonwealth Health Minister in August 1996.

PMID- 9629826
TI  - Nurses screening for skin cancer: an observation study.
AB  - Skin cancer rates in Australia are the highest in the world and it is an
      important cause of mortality and morbidity. Screening is a method of control for
      skin cancer/melanoma through early diagnosis and prompt referral and treatment.
      To date, there have been no controlled trials evaluating the impact of screening
      on morbidity and mortality, and hence insufficient evidence to recommend for or
      against routine screening for skin cancer/melanoma by primary care providers.
      Australian health authorities have called for studies that investigate the
      viability of using trained observers apart from medical practitioners--such as
      nurses, pharmacists and physiotherapists--in opportunistic screening for skin
      cancer in populations that have a high prevalence of these skin cancers, largely
      on the basis of cost arguments. We conducted a double blind observation screening
      study comparing the performance of nurses to those plastic surgeons participating
      in a skin cancer screening program. The role of the nurse in this program was not
      to diagnose skin cancer, but to not miss lesions that required further specialist
      examination. Measurements were recorded for 256 screenees. Plastic surgeons
      issued 77 (30%) individual referrals for lesions suspicious of being skin cancer.
      Nurse observations noted 73 (95%) of these 77 cases. The case for the pre
      screening of large populations for skin/cancer by trained nurses warrants further
      attention.

PMID- 9629827
TI  - Health care costs of a continuing epidemic of hepatitis C virus infection among
      injecting drug users.
AB  - OBJECTIVES: To estimate the direct health care costs of a continuing epidemic of
      hepatitis C virus (HCV) infection among injecting drug users (IDUs) in Australia
      from the formal health care system's perspective. DESIGN: A Markov cohort model
      is used to map the disease paths of successive hypothetical cohorts of 1,000
      patients as they develop the sequelae of HCV over an extended period of time.
      PATIENTS AND SETTING: IDUs becoming infected with HCV. OUTCOME MEASURES:
      Estimates of the number of persons in each of a limited number of disease states
      are used in conjunction with direct medical costs associated with ambulatory
      visits and inpatient hospital admissions over the course of the disease to
      estimate the long-term impact on the health care system of HCV infection among
      successive cohorts of IDUs. RESULTS: For every 1,000 IDUs newly infected with
      hepatitis C in a given year, there is an implied $14.32 million in health care
      spending over the years as sequelae become manifest, with cumulative total costs
      of some $0.5 billion (1994 dollars) after 60 years as the costs of successive
      cohorts of HCV-infected IDUs are added to the prevalence pool. If the estimated
      10,000 new HCV infections in IDUs in Australia per year continue for the next 60
      years, total direct health care costs will be around $4 billion over that period.
      CONCLUSIONS: Efforts to prevent HIV transmission among IDUs have been shown to be
      clearly cost-effective. These data imply that there is an even more pressing need
      to halt or slow the current epidemic of HCV infection among IDUs on fiscal
      grounds alone.

PMID- 9629828
TI  - Carbon monoxide exposures in Australian workplaces could precipitate myocardial
      ischaemia in smoking workers with coronary artery disease.
AB  - BACKGROUND: Quite low levels of carbon monoxide (CO) exposure have been shown
      experimentally to induce myocardial ischaemia in subjects with coronary artery
      disease. This study examines the actual exposure levels in Australian workplaces
      under normal operating conditions, to assess whether the resulting
      carboxyhaemoglobin (COHb) levels are high enough to present a risk of myocardial
      ischaemia in any workers who may have recognised or unrecognised coronary artery
      disease. METHODS: A total of 84 workers took part in the study, 60 of whom were
      working in an environment where a combustion process was taking place indoors and
      were therefore classified as exposed to CO. Ambient CO levels and end-expiratory
      CO levels (the latter as a predictor of COHb) were measured two-hourly and the
      number of cigarettes smoked over an eight-hour shift recorded. RESULTS: Mean
      workplace CO levels throughout the shift ranged between three and 12 ppm. Mean
      COHb ranged between 0.7% and 2.1% in non-smokers and 2.1%-7.6% in smokers, except
      for a single reading of 12.5% in forklift operations (one smoker). Exposed
      workers had significantly higher COHb levels than the non-exposed, both for
      smokers and non-smokers. Smoking also had an important independent effect on
      COHb. CONCLUSION: Under workplace conditions prevailing in industries where
      combustion processes are occurring indoors, CO exposures are unlikely to be high
      enough to cause myocardial ischaemia in non-smokers. However in a worker whose
      COHb is already raised from smoking, an increment from such occupational
      environments could be sufficient to induce myocardial ischaemia in workers with
      coronary artery disease.

PMID- 9629829
TI  - Labour-saving strategies to maintain survey response rates: a randomised trial.
AB  - To evaluate response-aiding strategies feasible in large surveys, we randomly
      allocated general practitioners (GPs) to one of four intervention groups: Group 1
      received 'exhaustive' telephone prompts by a medical peer in advance of a
      questionnaire; Group 2, inclusion of an embossed pen with the questionnaire;
      Group 3, an advance letter prompt; and Group 4, a 'single attempt' advance
      telephone prompt by a non-medical research assistant. Follow-up procedures were
      identical. Response rates by group were not significantly different overall (chi
      2 = 4.59, df = 3, p = 0.20) although advance prompts by a medical peer were
      significantly more effective than other strategies for male GPs. The difference
      in overall response rates between males (63%) and females (74%) was significant
      (chi 2 = 15.40, df = 1, p < 0.01). No other response bias was evident. Our
      demonstration of a significant interaction between respondent sex and response
      aiding strategy invites further research.

PMID- 9629830
TI  - Examination of skin naevi in Australian general practice: dissonance between care
      and need?
AB  - Over 26 months, 223 general practitioners recorded consultations involving the
      management of skin naevi and some demographic details of the patients. We used
      data from the Health Insurance Commission and the Australian Bureau of Statistics
      to estimate population consultation rates. Of 749,171 consultations, 9,729
      involved management of naevi. The annual rate per 1,000 of these consultation was
      11.3 (95% CI 11.0-11.6) for males and 17.0 (95% CI 16.6-17.5) for females. The
      rate was significantly higher in the 15-44 year age group, at 21.8 consultations
      per 1000 individuals annually, compared to 6.3 for younger ages and 16.0, 16.1
      and 8.6 for the 45-64, 65-74 and 75+ age groups respectively. There was a
      seasonal variation, with rates highest in the hot months (of about 16 annual
      consultations per 1,000 individuals) and lowest in the cooler months (14 for the
      two years' cooler seasons sampled). There was a significant variation between the
      rates of different states and territories, but this did not follow a latitude
      difference. There is a dissonance between the distribution of melanomas
      (relatively concentrated among older patients and males) and the general practice
      management of skin naevi (relatively concentrated among younger patients and
      females). Although melanomas (particularly those with the poorest prognosis) are
      relatively concentrated in older men, paradoxically, more skin naevi are managed
      in general practice among younger and female patients.

PMID- 9629831
TI  - Prostate cancer testing in SA men: influence of sociodemographic factors, health
      beliefs and LUTS.
AB  - This study investigates the prevalence and determinants of prostate cancer
      screening in the South Australian community. An interview-based survey of a
      probability sample of the SA population (N = 3,016) in 1995 addressed previous
      PSA testing, beliefs about vulnerability to prostate cancer and efficacy of
      screening, presence of uncomplicated lower urinary tract symptoms (LUTS) and
      sociodemographic variables. Of 736 men, 40 years and over with no history of
      prostate cancer, 24.7% (182/736) reported ever having had a test and 53.9% (397)
      reported an intention to test; 74% (547) agreed that prostate cancer could be
      cured if detected early, while only 14.9% (109) believed they were unlikely to
      suffer from prostate cancer. In a logistic regression model, visit to a doctor
      for (but not presence of) LUTS was a strong, independent predictor of
      participation in PSA testing (OR 9.0, 95% CI 5.0, 16.0). Beliefs, occupation and
      education were not. In a similar model examining intention to test, belief in
      vulnerability to prostate cancer was the strongest predictor (OR 3.32, 95% CI
      1.9, 5.9), followed by doctor visit for urinary symptoms. These data are
      consistent with widespread PSA testing and with seeking treatment for LUTS being
      a major determinant of previous testing. NHMRC Clinical Guidelines for LUTS
      recommend against PSA testing for investigation of uncomplicated LUTS.
      Implementation of those guidelines may therefore have a significant effect on PSA
      testing rates. Belief in personal vulnerability to prostate cancer remains a
      significant component of reported future testing, suggesting a focus for
      community education.

PMID- 9629832
TI  - Science's great tragedy.

PMID- 9629833
TI  - Postmodernism and public health.

PMID- 9629834
TI  - Community panics about mobile phone towers.

PMID- 9629835
TI  - First known outbreak of colonizing vancomycin-resistant enterococci in Quebec.

PMID- 9629836
TI  - Progress towards elimination of measles in the Americas. WHO expanded programme
      on immunization.

PMID- 9629837
TI  - What's in a name? Amyotrophic lateral sclerosis, motor neuron disease, and
      allelic heterogeneity.

PMID- 9629838
TI  - Neurological manifestations of falciparum malaria.
AB  - Plasmodium falciparum remains one of the most common causes of central nervous
      system infection worldwide. Recently, differences between the pathophysiology of
      cerebral malaria in African children and nonimmune adults have been discovered,
      new syndromes occurring after malaria infection described, and mechanisms for the
      pathogenesis proposed. In addition, new antimalarial agents have been examined
      worldwide and initial studies on supportive studies conducted. This paper reviews
      these new advances, putting them into the perspective of the more established
      knowledge.

PMID- 9629839
TI  - Limited corticospinal tract involvement in amyotrophic lateral sclerosis subjects
      with the A4V mutation in the copper/zinc superoxide dismutase gene.
AB  - We examined 11 subjects with inherited amyotrophic lateral sclerosis (familial
      amyotrophic lateral sclerosis, FALS) associated with the most common copper/zinc
      superoxide dismutase 1 (SOD1) mutation, an alanine for valine substitution in
      codon 4 (A4V). Autopsies were performed on 5 subjects. The clinical and
      pathological findings are described and compared with those of 9 sporadic ALS
      (SALS) subjects. There was no clinical evidence of upper motor neuron (UMN)
      involvement in 10 FALS A4V subjects. All subjects had lower motor neuron (LMN)
      signs and electrophysiological evidence of denervation in at least three limbs.
      All SALS subjects had signs of both UMN and LMN involvement. Pathological studies
      found severe abnormalities of LMNs in all FALS and SALS subjects. UMN involvement
      was either absent or mild in the A4V SOD1 FALS subjects and severe in the SALS
      subjects. Pathological abnormalities in systems other than the motor neurons were
      more frequent in the FALS A4V subjects. This information suggests that current
      diagnostic criteria for ALS, requiring dinical evidence for both upper and lower
      motor neuron involvement, should be modified; ie, the diagnosis should be deemed
      established when there is evidence of denervation in three or more limbs and a
      mutation in the gene for SOD1, even without dinical signs of UMN involvement.

PMID- 9629840
TI  - Serotonin inhibits trigeminal nucleus activity evoked by craniovascular
      stimulation through a 5HT1B/1D receptor: a central action in migraine?
AB  - The development of serotonin (5HT1B/1D) agonists as treatments for the acute
      attack of migraine has resulted in considerable interest in their mechanism of
      action and, to some extent, renewed interest in the role of serotonin (5
      hydroxytryptamine; 5HT) in the disorder. The initial synthesis of this class of
      compounds was predicated on the clinical observation that intravenous 5HT
      terminated acute attacks of migraine. In this study the superior sagittal sinus
      was isolated in the alpha-chloralose (60 mg/kg i.p. and 20 mg/kg i.v. injection
      supplementary 2 hourly) anesthetized cat. The sinus was stimulated electrically
      (120V, 250 microsec duration, 0.3 Hz), and neurons of the trigeminocervical
      complex in the dorsal C2 spinal cord were monitored using electrophysiological
      methods. After baseline recordings in each animal, 5HT (15 microg/kg/min) was
      infused for 5 minutes in the presence of either vehicle (group A) or the 5HT1B/1D
      antagonist GR127935 (100 microg/kg i.v. injection; group B). The baseline
      probability of cell firing after sagittal sinus stimulation was 0.61 +/- 0.1 at a
      latency to the fastest peak of 11.1 +/- 0.4 msec. In group A, 5HT infusion alone
      had a small effect of increasing mean blood pressure (12 +/- 3 mm Hg), which in
      itself did not alter cell firing. In group A, 5HT alone had an inhibitory effect
      on evoked trigeminal activity, which developed 15 to 20 minutes after
      commencement of the infusion. The inhibition of cell firing lasted for 20
      minutes, after which the activity returned to baseline. In group B, the
      combination of 5HT and GR127935 had no effect on trigeminal cell firing, although
      the small hypertensive effect was still present. These data indicate that 5HT
      inhibits evoked trigeminal nucleus firing via the 5HT1B/1D receptor at which
      GR127935 is an antagonist. It is likely that some part of the effect of 5HT in
      migraine relates to inhibition of trigeminal nucleus activity, just as it is
      likely that some part of the effect of the triptans is also mediated at this
      central site and may be complementary to their nonneuronal actions. Moreover, the
      data highlight the case for describing this class of headache as neurovascular
      headaches rather than vascular headaches, to recognize the implicit contribution
      of the trigeminovascular system to their pathophysiology.

PMID- 9629841
TI  - Amyloid myopathy: an underdiagnosed entity.
AB  - Amyloidosis can involve multiple organs, including kidney, heart, peripheral
      nerve, skin, joints, and skeletal muscle, but rarely presents as a myopathy. We
      studied 13 adults with muscle weakness for between 3 months and 4 years in whom
      the diagnosis of systemic amyloidosis was unsuspected before or until just before
      the time of the muscle biopsy. All muscle specimens demonstrated congophilic
      deposits around blood vessels and muscle fibers, some necrotic and regenerating
      fibers, and signs of mild denervation. Immunostains in 10 patients revealed
      immunoglobulin amyloidosis in 7 and gelsolin amyloidosis in 1. Apolipoprotein E
      co-localized with the congophilic deposits in all 10, and a C-terminal epitope of
      the beta-amyloid precursor protein was detected in 6. The frequency of the
      diagnosis of amyloid myopathy increased 10-fold when we adopted the fluorescent
      Congo red stain as a routine procedure in assessing muscle biopsy specimens.

PMID- 9629842
TI  - Fast eye movement initiation of ocular torsion in mesodiencephalic lesions.
AB  - Three patients with episodic ocular torsion and skew deviation due to
      mesodiencephalic lesions were studied by using binocular three-dimensional
      scleral search coils. The conjugate ocular torsion (upper pole of each eye
      rotating toward the side of the brainstem lesion) was initiated by a torsional
      fast eye movement. During prolonged episodes, torsional nystagmus was also
      present. Cessation of the ocular torsion and skew deviation occurred by slow eye
      movements with exponentially decreasing velocities in 2 patients, and by multiple
      fast torsional movements in 1 patient. In 1 patient, the abnormal eye movements
      were temporally linked to dystonic movements in the limbs on the side opposite
      the brainstem lesion. The occurrence of skew deviation with conjugate ocular
      torsion in brainstem lesions has been attributed to functional asymmetry in
      vestibular pathways responsible for the slow-phase compensatory eye movement
      response to roll. In comparison, the findings in our patients show that in
      mesodiencephalic lesions conjugate ocular torsion with skew deviation may be
      generated by torsional fast eye movements, indicating activation of the burst
      cells of the rostral interstitial nucleus of the medial longitudinal fasciculus.

PMID- 9629843
TI  - Cyclooxygenase-2 is induced globally in infarcted human brain.
AB  - Cyclooxygenase (COX) catalyzes synthesis of prostanoids after liberation of
      arachidonic acid, an important biochemical sequela of cerebral ischemia that
      aggravates brain injury. We investigated expression of inducible COX-2 in
      infarcted human brains (symptom duration, 15 hours to 18 days) and found that COX
      2 protein was present in both neuronal and glial cells throughout the brain in
      accord with infarct topography and duration. These results emphasize the global
      yet temporally regulated nature of COX-2 induction during focal ischemia in
      humans, clearly different from the circumscribed acute expression reported in
      experimental animal models. We speculate that early induction of COX-2 may fuel
      tissue damage through prostanoids and free radicals, and delayed induction in
      remote brain areas may promote reconstitutive processes in the face of tissue
      scarring and remodeling of the surviving neural networks.

PMID- 9629844
TI  - Temporal distribution of partial seizures: comparison of an animal model with
      human partial epilepsy.
AB  - Seizures do not often strike randomly but may occur in circadian patterns. We
      compared daily times of partial seizures determined by continuous
      electroencephalography among patients with mesial temporal lobe epilepsy (MTLE; n
      = 64), those with extratemporal lobe (XTLE; n = 26) or lesional temporal lobe
      epilepsy (LTLE; n = 8), and a rat model similar to MTLE in which rats become
      epileptic after electrically induced limbic status epilepticus (postlimbic status
      [PLS]; n = 20). Rats were maintained on a 12-hour light/dark cycle with lights on
      at 0700 hours. The distributions of seizures were fitted by cosinor analysis to
      determine time of peak seizure incidence +/- 95% confidence interval (95% CI).
      The mean fraction +/- SD of seizures recorded during light was 63 +/- 17% in PLS
      animals and 60 +/- 21% in humans. Peak incidence of seizures for PLS rats (547
      seizures) was 1645 (95% CI = 1448,1830) and for MTLE subjects (774 seizures) was
      1500 (95% CI = 1324,1636). Seizures from XTLE (465 seizures) and LTLE (48
      seizures) did not fit a cosinor model and occurred no more frequently during
      light than dark. In conclusion, limbic seizures in humans and PLS rats occur more
      often during light than dark and have similar cosinor daily distributions. The
      chronological similarity between human MTLE and PLS rat epilepsy suggests that
      limbic seizure occurrence has a relation to the circadian regulatory system.

PMID- 9629845
TI  - Temporal ictal electroencephalographic frequency correlates with hippocampal
      atrophy and sclerosis.
AB  - We studied 328 complex partial seizures (CPS) in 63 consecutive patients with
      temporal lobe epilepsy who underwent scalp electroencephalography/video
      monitoring, magnetic resonance imaging (MRI), and surgery. The initial ictal
      discharge (IID), defined as the first sustained electrical seizure pattern
      localized to the surgical site, was determined. If the IID was rhythmic waves,
      the median frequency was measured. To determine if IID frequency correlates with
      hippocampal atrophy (HA) or sclerosis (HS), hippocampal volume ratios (HVRs) were
      measured (n = 52) or assessed visually (n = 11) on MRI, and mesial temporal
      histopathology specimens (n = 22) were graded for HS. Sixteen patients (25%) had
      no or mild HA (HVR = 0.78-1.02), and 47 patients (75%) had moderate-to-marked
      unilateral (HVR = 0.33-0.76), or bilateral, HA. Theta frequency IIDs were
      significantly more commonly associated with moderate-to-marked HA than were delta
      IIDs. Theta frequency IIDs occurred in 19% of patients with mild or no HA, and
      79% of patients with moderate-to-marked HA; delta IIDs occurred in 63% of
      patients with little to no HA, and 13% of those with moderate-to-marked HA. In
      addition, the median IID frequency inversely correlated with HVR and directly
      correlated with HS severity. In conclusion, faster frequency rhythmic IIDs during
      temporal lobe CPS correlate with greater degrees of ipsilateral HA on MRI, and
      higher grades of HS.

PMID- 9629846
TI  - Descriptive epidemiology of Creutzfeldt-Jakob disease in six European countries,
      1993-1995. EU Collaborative Study Group for CJD.
AB  - After the occurrence of bovine spongiform encephalopathy (BSE), there has been
      concern that transmission of BSE to the human population might result in a change
      in the epidemiological characteristics of Creutzfeldt-Jakob disease (CJD). A
      collaborative study of CJD in the European Union was performed from 1993 to 1995,
      to compare data from national registries for CJD in France, Germany, Italy, The
      Netherlands, Slovakia, and the United Kingdom. Five hundred seventy-five patients
      with definite or probable CJD died in the study period with an overall annual
      mortality rate of 0.71 cases per million. The incidence rates for CJD were
      similar in all participating countries despite variations in postmortem rates,
      and age-specific incidence rates were also relatively consistent, with the
      exception of an increased incidence of CJD in patients younger than 39 years of
      age in the United Kingdom. In relation to etiological subtypes of CJD, 87% of
      cases were sporadic, 8% genetic, and 5% iatrogenic. Genetic forms of CJD
      comprised 80% of all cases in Slovakia, and iatrogenic forms of CJD occurred most
      frequently in France and the United Kingdom. The statistical data reported here
      do not provide evidence of a causal link between BSE and CJD in Europe as a
      whole. However, the study has established baseline epidemiological parameters for
      CJD in participating European countries, which may be important in the assessment
      of any future change in the characteristics of CJD as a result of the epidemic of
      BSE.

PMID- 9629847
TI  - Hereditary form of parkinsonism--dementia.
AB  - In four generations of a family, 13 members were afflicted with an autosomal
      dominant disorder characterized by young age at onset, early weight loss, and
      rapidly progressive dopa-responsive parkinsonism, followed later by dementia and,
      in some, by hypotension. Intellectual dysfunction began with subjective memory
      loss and objective visuospatial dysfunction and was followed later by decline of
      frontal lobe cognitive and memory functions. Neuropathological examination in 4
      autopsied cases showed neuronal loss in the substantia nigra and locus ceruleus
      and widespread Lewy bodies, many of them in the cerebral cortex; those in the
      hypothalamus and locus ceruleus were often of bizarre shapes. Other findings were
      vacuolation of the temporal cortex, unusual neuronal loss and gliosis in the
      hippocampus (CA 2/3), and neuronal loss in the nucleus basalis. There were no
      neuritic plaques, neurofibrillary tangles, or amyloid deposits. Positron emission
      tomography in 3 patients showed decreased striatal uptake of fluorodopa.
      Neurochemical analysis of an autopsied brain showed a pronounced decrease in
      choline acetyltransferase activity in the frontal and temporal cortices and
      hippocampus and a severe depletion of striatal dopamine with a pattern not
      typical of classic Parkinson's disease.

PMID- 9629848
TI  - Neuroanatomical and neurocognitive differences in a pair of monozygous twins
      discordant for strictly defined autism.
AB  - In this study, we investigated the neuroanatomical similarities and differences
      between a pair of monozygotic, 7.5-year-old twin boys discordant for strictly
      defined autism, to identify neuroanatomical pathways that are impaired in
      individuals with autism. Although the unaffected twin did not fulfill the
      traditional diagnostic criteria for autism, he displayed constrictions in social
      interaction and play that were consistent with the broader phenotype for autism
      that has been described in nonautistic co-twins. Magnetic resonance imaging scans
      were obtained for each brother and compared with the scans of 5 age- and sex
      matched unaffected peers. Quantitative analysis of brain anatomy revealed that
      the affected twin had markedly smaller caudate, amygdaloid, and hippocampal
      volumes, and smaller cerebellar vermis lobules VI and VII, in comparison with his
      brother. Both twins evidenced disproportionately reduced volumes of the superior
      temporal gyrus and the frontal lobe relative to the comparison sample. The
      results suggest the dysfunction of two separate but overlapping neuroanatomical
      pathways, ie, one subcortical network differentiating the twins from each other
      that may underlie the traditional neurobehavioral phenotype for strictly defined
      autism, and a second cortical network differentiating the twins from the
      comparison sample that may lead to the broader phenotype for autism.

PMID- 9629849
TI  - Dopamine transporter density measured by [123I]beta-CIT single-photon emission
      computed tomography is normal in dopa-responsive dystonia.
AB  - The clinical distinction between dopa-responsive dystonia (DRD) and juvenile
      Parkinson's disease JPD) can pose a diagnostic challenge. Both conditions are
      dopa responsive. However, long-term L-dopa benefit is very different between the
      two. The difference in the prognosis is due to presence or absence of nigral cell
      loss. In JPD, there is degenerative nigral cell loss, whereas there are enzymatic
      defects in dopamine synthesis without cell loss in DRD. Mutations have been found
      in the GTP cyclohydrolase I (GCH-I) and tyrosine hydroxylase genes in DRD. As the
      discovered mutations are multiple and more are expected to be found, it is
      difficult to confirm or exclude DRD by mutation studies. Measurement of
      cerebrospinal fluid (CSF) neopterin will detect DRD from mutations in the GCH-I
      gene but not from mutations in tyrosine hydroxylase. The dopamine transporter
      (DAT) is a protein in the dopaminergic nerve terminals. (1R)-2beta-Carbomethoxy
      3beta-(4-[123I]iodophenyl)tropane ([123I]beta-CIT) is a ligand for the DAT, and
      it was shown to be a useful nuclear imaging marker for neurons that degenerate in
      Parkinson's disease (PD). As DRD was shown to have a normal DAT without nigral
      cell loss in a postmortem study, we predicted that the DAT measured in vivo by
      nuclear imaging will be normal in DRD and will differentiate DRD from JPD.
      Therefore, we performed [123I]beta-CIT single-photon emission computed tomography
      ([123I]beta-CIT SPECT) in clinically diagnosed DRD, PD, and JPD, and examined
      whether DAT imaging can differentiate DRD from PD and JPD. We then examined
      whether DAT imaging can provide a screening tool for molecular genetic studies,
      by studying mutations in the candidate gene GCH-I and measuring CSF neopterin.
      Five females (4 from two families, and 1 sporadic) were diagnosed as DRD based on
      early-onset foot dystonia and progressive parkinsonism beginning at ages 7 to 12.
      All patients were functioning normally on L-dopa 100 to 250 mg/day for up to 8
      years. SPECT imaging was obtained after intravenous injection of [123I]beta-CIT;
      15 healthy volunteers served as normal control, and 6 PD and 1 JPD as disease
      controls. [123I]beta-CIT striatal binding was normal in DRD, whereas it was
      markedly decreased in PD and JPD. Gene analysis showed a novel nonsense mutation
      in the GCH-I gene in one family. No mutation was found in the other family or in
      the sporadic case. CSF neopterin was markedly decreased in the 4 tested patients.
      [123I]beta-CIT SPECT is a sensitive method for probing the integrity of
      nigrostriatal dopaminergic nerve terminals. A normal striatal DAT in a
      parkinsonian patient is evidence for a nondegenerative cause of parkinsonism and
      differentiates DRD from JPD. Finding a new mutation in one family and failure to
      demonstrate mutations in the putative gene in other cases supports the usefulness
      of DAT imaging in diagnosing DRD.

PMID- 9629850
TI  - Dynamic [18F]fluorodeoxyglucose positron emission tomography and hypometabolic
      zones in seizures: reduced capillary influx.
AB  - We performed dynamic [18F]fluorodeoxyglucose ([18F]FDG) positron emission
      tomographic (PET) analyses in 8 patients. Rate constants of influx (K1*), efflux
      (k2*), phosphorylation (k3*), and dephosphorylation (k4*) were derived for the
      regions of interest (ROIs), which included (1) the hypometabolic epileptogenic
      regions and (2) the homologous regions in the contralateral hemispheres. In
      addition, the four constants were determined from at least one clearly defined
      (control) ROI from the same plane and its homologous contralateral ROI. Influx
      (K1*) in the epileptogenic region was reduced in comparison with the
      contralateral ROI. Reductions in influx (K1*), which averaged 18 +/- 13% (mean +/
      SD), [18F]FDG phosphorylation (k3*) (25 +/- 20%), and brain glucose utilization
      rates (26 +/- 10%) were observed in the epileptogenic region. Reductions in
      efflux were not statistically significant (k2* = 13 +/- 28%) but were comparable
      in magnitude to the average reduction in K1*. No ipsilateral versus contralateral
      differences were seen for any rate constants measured outside the epileptogenic
      region. Influx correlated highly with phosphorylation in the epileptogenic
      region. Our data suggest that the hypometabolic epileptogenic focus seen in
      [18F]FDG-PET studies is also a region of reduced blood-brain barrier glucose
      transporter activity and that reductions in phosphorylation are proportional to
      reductions in [18]FDG influx.

PMID- 9629851
TI  - Magnetization transfer changes in the normal appearing white matter precede the
      appearance of enhancing lesions in patients with multiple sclerosis.
AB  - Serial monthly magnetization transfer (MT) imaging was performed to evaluate
      whether a change of the normal appearing white matter (NAWM), which precedes the
      appearance of enhancing lesions, is seen in patients with multiple sclerosis
      (MS). Every 4 weeks for 3 months, 10 patients with relapsing-remitting MS were
      scanned with a T1-weighted sequence, 20 minutes after injection with 0.3 mmol/kg
      gadolinium-DTPA (Gd-DTPA). During each of the monthly sessions, MT and dual echo
      scans were also performed before Gd-DTPA injection. On coregistered images, the
      MT ratio (MTR) was measured in NAWM subsequently involved by enhancing lesions,
      in NAWM areas on the same slices but outside any present or future MR
      abnormality, and in enhancing lesions at the time of their appearance. Forty
      eight new enhancing lesions with no corresponding abnormalities on previous scans
      were identified. Their average MTR was 33.1% (+/-8.4%). Three, 2, and 1 month
      before enhancement appearance, the mean MTR in NAWM, measured from areas
      corresponding to future enhancing lesions, was significantly lower than the mean
      MTR in NAWM outside enhancing areas; the MTR decreased steadily as the time when
      the enhanced lesion approached. These results suggest that changes in the NAWM of
      patients with MS occur before lesions become evident on conventional MRI scans.

PMID- 9629852
TI  - Tau is a candidate gene for chromosome 17 frontotemporal dementia.
AB  - Frontotemporal dementia with parkinsonism, chromosome 17 type (FTDP-17), a
      recently defined disease entity, is clinically characterized by personality
      changes sometimes associated with psychosis, hyperorality, and diminished speech
      output, disturbed executive function and nonfluent aphasia, bradykinesia, and
      rigidity. Neuropathological changes include frontotemporal atrophy often
      associated with atrophy of the basal ganglia, substantia nigra, and amygdala.
      Neurofibrillary tangles (NFTs) are seen in some but not all families. Inheritance
      is autosomal dominant and the gene has been regionally localized to 17q21-22 in a
      2- to 4-centimorgan (cM) region flanked by markers D17S800 and D17S791. The gene
      for tau, the primary component of NFTs, is located in the same region of
      chromosome 17. Tau was evaluated as a candidate gene. Physical mapping studies
      place tau within 2 megabases or less of D17S791, but it is probably outside the
      D17S800-D17S791 FTDP-17 interval. DNA sequence analysis of tau coding regions in
      affected subjects from two FTDP-17 families revealed nine DNA sequence variants,
      eight of which were also identified in controls and are thus polymorphisms. A
      ninth variant (Val279Met) was found in one FTDP-17 family but not in the second
      FTDP-17 family. Three lines of evidence indicate that the Val279Met change is an
      FTDP-17 causative mutation. First, the mutation site is highly conserved, and a
      normal valine is found at this position in all three tau interrepeat sequences
      and in other microtubule associated protein tau homologues. Second, the mutation
      co-segregates with the disease in family A. Third, the mutation is not found in
      normal controls.

PMID- 9629853
TI  - Codon 219 Lys allele of PRNP is not found in sporadic Creutzfeldt-Jakob disease.
AB  - The polymorphism at codon 219 of the prion protein gene (PRNP) was found in the
      general Japanese population with 6% allele frequency. Herein, we examined 85
      cases of sporadic Creutzfeldt-Jakob disease (CJD) for the codon 219 polymorphism.
      The codon 219Glu/Lys heterozygous polymorphism was not found in these CJD cases.
      In addition, we examined 43 patients with dementia of non-CJD origin, and 4 were
      found to have the codon 219Glu/Lys heterozygous polymorphism with a similar
      allele frequency as in the general population. Thus, the codon 219Glu/Lys
      heterozygous polymorphism might be uniquely excluded from sporadic CJD.

PMID- 9629854
TI  - N-glycolylneuraminic acid-containing GM1 is a new molecule for serum antibody in
      Guillain-Barre syndrome.
AB  - To clarify the pathogenesis of Guillain-Barre syndrome (GBS) after parenteral
      injections of bovine brain gangliosides, we searched for new molecules in bovine
      brain gangliosides recognized by sera from GBS patients. Gangliosides
      fractionated in a Q-Sepharose column were used as the antigens, and the binding
      of serum IgG or IgM was examined by thin-layer chromatography/immunostaining.
      Fourteen of 175 serum samples from the patients reacted with the
      monosialoganglioside fraction 2. In the neutral solvent system, a band in this
      fraction migrated with N-acetylneuraminic acid-containing GM1 [GM1(NeuAc)],
      whereas in the alkaline solvent system it migrated slower. This suggested that
      the band was N-glycolylneuraminic acid-containing GM1 [GM1(NeuGc)]. In both
      solvent systems, its mobility was almost the same as that of authentic GM1(NeuGc)
      from mouse liver. Secondary ion mass spectrometry showed that the ganglioside's
      structure was consistent with that of GM1(NeuGc). IgG anti-GM1(NeuGc) antibodies
      in sera from the GBS patients were significantly absorbed by GM1(NeuAc),
      indicative that the anti-GM1(NeuGc) antibodies cross-react with GM1(NeuAc). N
      Glycolylneuraminic acid-containing gangliosides are so highly immunogenic in
      humans that the injection of GM1(NeuGc) could induce the production of IgG anti
      GM1(NeuGc) antibody, which cross-reacts with GM1(NeuAc).

PMID- 9629855
TI  - MELAS exhibits dominant negative effects on mitochondrial RNA processing.

PMID- 9629856
TI  - Identical mitochondrial DNA in monozygotic twins with discordant
      adrenoleukodystrophy phenotype.

PMID- 9629857
TI  - Skin vasomotor reflex in a patient with brainstem dysfunction.

PMID- 9629858
TI  - Decreased nitrogen rates and irrigation effect on celery yield and internal
      quality.
AB  - The effect of decreased nitrogen rates (90, 60 and 30 kg N/ha) with and without
      irrigation on celery yield quantity and internal quality were studied in field
      experiments in 1993 and 1994. The decreased nitrogen rates reduced yields in both
      years. In the dry and warm conditions of 1994 nitrogen x irrigation interaction
      was clearly observed; irrigation increased yield more at higher nitrogen rates
      than at lower nitrogen rates. In the rainy conditions of 1993 irrigation did not
      effect the yield level. On the other hand, in both years, decreased nitrogen
      rates increased dry matter, vitamin C and dietary fiber contents, and nitrogen
      had a minor effect on total sugar content. In 1994 alpha- and beta carotene and
      thiamin were also analyzed but nitrogen had no effect on them. Irrigation
      increased dry matter and total sugar contents at the two lowest nitrogen rates in
      1994, but decreased vitamin C contents in both years. There was also slight
      evidence that irrigation might decrease alpha- and beta-carotene and thiamin
      contents.

PMID- 9629859
TI  - Effect of extrusion processing on the soluble and insoluble fiber, and phytic
      acid contents of cereal brans.
AB  - The health benefits associated with dietary fiber have resulted in it now being
      used in virtually all food product categories, including many products which are
      manufactured using extrusion processing. The objective of the present study was
      to determine if extrusion processing affected phytic acid, and soluble and
      insoluble fiber contents. The effect of screw speeds of 50, 70, and 100% of
      maximum rotations per minute (% MRPM) on these components was investigated. A BI
      EX Model DNDG-62/20D co-rotating intermeshing self-cleaning twin-screw extruder,
      manufactured by Buhlerag, CH-9240, Uzwil, Switzerland, was used to process wheat,
      oat and rice brans. It was found that extrusion did not affect the insoluble
      fiber content of wheat bran; however, a decrease in this component was observed
      in rice and oat brans. The effect on rice bran insoluble fiber was greatest at
      screw speeds of 50 and 70% MRPM. This occurred in oat bran at 50% MRPM. Soluble
      fiber content increased in all brans after extrusion, except ER100. For oat and
      rice bran soluble fibers, the greatest increase occurred at 50 and 70% MRPM,
      while for wheat bran this occurred at 70 and 100% MRPM. Extrusion did not affect
      the phytate content of the cereal brans.

PMID- 9629860
TI  - Soluble and insoluble fiber contents of some Cameroonian foodstuffs.
AB  - As a result of the lack of reliable data on the fiber content of African
      foodstuffs, a study to determine the dietary fiber contents (soluble, insoluble
      and total) on a dry weight basis of a selected variety of major Cameroonian foods
      was conducted. The influence of processing and preparation methods on the fiber
      content was also assessed. Vegetables were found to be the richest source of
      total dietary fiber (57%), followed by legumes and seeds (30%) and fruits
      (16.5%). Okro (Hibiscus esculenta), plantain (Musa paradisiaca) and beans
      (Phaseolus spp) showed varietal differences in their soluble and insoluble fiber
      content, while methods of processing and preparation significantly influenced the
      fiber content of cassava (Manihot esculenta), corn (Zea mays) and beans.

PMID- 9629861
TI  - Effect of processing on flatus producing oligosaccharides in cowpea (Vigna
      unguiculata) and the tropical African yam bean (Sphenostylis stenocarpa).
AB  - The effect of dehulling, soaking and soaking/cooking on sucrose, raffinose and
      stachyose in mature dry seeds of nine varieties of cowpea (Vigna unguiculata) and
      one variety of tropical African yam bean (Sphenostylis stenocarpa) were
      investigated. The results showed a progressive decrease in sucrose, raffinose,
      and stachyose contents. Soaking for 12 hours and cooking for 30 min eliminated
      most of the sucrose, raffinose and stachyose. The sugar contents in whole raw
      cowpea were sucrose 0.73-4.58%, raffinose 0.71-6.86% and stachyose 2.38-3.87%,
      and for tropical African yam bean sucrose 4.08%, raffinose 1.08% and stachyose
      4.14% while the seeds soaked for 12 hours and cooked for 30 min had for cowpea
      sucrose 0.03-0.81%, raffinose 0.04-0.20% and stachyose 0.12-0.72%, and tropical
      African yam bean sucrose 0.70%, raffinose 0.40% and stachyose 0.41%.

PMID- 9629862
TI  - Lipid profile of rats fed blends of rice bran oil in combination with sunflower
      and safflower oil.
AB  - This study was undertaken to assess the effect of blended oils, i.e.,
      polyunsaturated fatty acid (PUFA) rich vegetable oils like safflower oil (SFO)
      and sunflower oil (SNO) with the unconventional and hypocholesterolemic rice bran
      oil (RBO) on the serum lipid profile of rats. Rats fed RBO+SNO/SFO at 70:30 ratio
      for a period of 28 days showed significantly (p < 0.05) lower levels of total
      cholesterol (TC), triglycerides (TG) and low density lipoprotein (LDL)
      cholesterol and increased high density lipoprotein (HDL) cholesterol in animals
      fed a high cholesterol diet (HCD) and cholesterol free diet (CFD). Liver total
      cholesterol (TC) and triglycerides (TG) were also reduced. Fecal excretion of
      neutral sterols and bile acids was increased with use of RBO blends. RBO, which
      is rich in tocopherols and tocotrienols, may improve the oxidative stability of
      the blends. Tocotrienols are known to inhibit 3-hydroxy, 3-methyl, glutaryl CoA
      (HMG-COA) reductase (rate limiting enzyme in cholesterol biosynthesis), resulting
      in hypocholesterolemia. In addition to improving the lipid profile by lowering
      TC, TG and LDL-C and increasing HDL-C, blending of RBO with other oils can result
      in an economic advantage of lower prices.

PMID- 9629863
TI  - Recent advances in caffeine and theobromine toxicities: a review.
AB  - Caffeine and theobromine are purine alkaloids widely consumed as stimulants and
      snacks in coffee and cocoa based foods and most often as part of ingredients in
      drugs. Man has enjoyed a long history of consumption of caffeine and theobromine.
      Recent interest in these two alkaloids, however, is centered on their potential
      reproductive toxicities. Caffeine and theobromine are now known to cross the
      placental and blood brain barrier thus potentially inducing fetal malformation by
      affecting the expression of genes vital in development. The developing fetus may
      not have developed enzymes for detoxification of these methylxanthine alkaloids
      via demethylation. There is a need, therefore, to protect the conceptus against
      'insults' from teratogens of this nature. Apart from its reproductive toxicity,
      the presence of caffeine and theobromine in cocoa could limit its potentials as a
      nourishing food. This is an issue that needs to be addressed by nutritionists and
      the food industry at large. This paper discusses the natural sources, consumption
      and uses, toxicity and the major advances in the reproductive toxicology of
      caffeine and theobromine. The biosynthesis of these compounds in plants,
      metabolism in mammalian systems and the involvement of cytochrome P450 are
      reviewed and summarized. Evidence in favor of the toxicity of these compounds in
      experimental animals is presented with emphasis on the implications of these
      findings in humans. The paper concludes with a call for caution in the use of
      caffeine and theobromine pending further and more elaborate investigations.

PMID- 9629864
TI  - Emulsifying properties of three African food hydrocolloids: okra (Hibiscus
      esculentus), dika nut (Irvingia gabonensis), and khan (Belschmiedia sp.).
AB  - This study investigated the emulsifying properties of okra (Hibiscus esculentus),
      dika nut (Irvingia gabonensis) and khan (Belschmiedia sp.), three African food
      hydrocolloids used to thicken and flavor soups. Results showed that khan has an
      emulsion potential approximately 20 and 100 times higher than the second and the
      first, respectively. A kinetic study indicated that the mechanism involved
      formation of thick and strong interfacial gum films around the oil globules, in
      addition to a high Water Absorption Capacity and weak gelling behavior of khan
      gum in solution. These results indicated that, when used in soups, which are
      typical oil/water emulsions, khan contribute both to thickening and stabilizing
      of the emulsion, whereas okra and dika nut functioned more as thickeners than as
      emulsion stabilizers.

PMID- 9629865
TI  - Dietary secondary amines and liver hepatoma in Port Harcourt, Nigeria.
AB  - Dietary secondary amines of some Nigerian foodstuffs were analyzed by Soxhlet
      extraction, using petroleum ether (b.p. 60-80 degrees C); followed by thin layer
      chromatography developed in a solvent system; n-butanol: 95% ethanol: water
      (4:2:1) for the qualitative test. Each UV fluorescent band in the test
      chromatogram was scraped and eluted with distilled water, filtered and assayed
      for secondary amine content for the quantitative test. Quantitative estimations
      were by the colorimetric methods. The results show that Ugu--Telfairia
      occidentalo; millet--Panicum miliaceum; bitter leaf--Vernonia amygdalina;
      mushroom--Boletus spp; and Okro--Hibiscus esculentus contain diethylamine,
      dimethylamine, morpholine and ethylaniline. Garri--Manihot utilissima flour
      contains diethylamine and dimethylamine only; while fish (frozen) Tilapia
      malanopleura contains diethylamine, dimethylamine and piperidine and the smoked
      fish--Tilapia nilotica contains diethylamine, dimethylamine, ethylaniline,
      morpholine, piperidine and n-propylamine. Cocoyam--Xanthosoma sagittifolium
      contains diethylamine, dimethylamine, morpholine, ethylaniline and proline. The
      results also show that the secondary amine content of the various foodstuffs
      ranged between 0.80-0.91 microg N/kg. The public health implications of these
      findings are discussed.

PMID- 9629866
TI  - Chemical and sensory evaluation of vegetable milks from African yam bean
      Sphenostylis stenocarpa (Hochst ex A Rich) Harms and maize (Zea mays L.).
AB  - Vegetable milks were developed from fermented and unfermented African yam bean
      (AYB) flours and their maize blends. AYB was cleaned, dehulled, milled and
      fermented for 24 hours by the natural microflora present in the legume flour.
      Maize was fermented for 48 hours. A ratio of 70:30 (protein basis) of AYB: maize
      was used to formulate the blends. Vegetable milks were prepared from the AYB
      flours and their maize blends. Standard assay techniques were used to evaluate
      the milks for proximate, mineral, ascorbate and antinutrient composition. The
      protein contents of the milks (1.47-2.06 percent) was comparable to soymilk (2.04
      percent) and bambara groundnut milk (2.00 percent). The milks contained
      appreciable quantities of carbohydrate and minerals tested. The milk blends had
      traces of ascorbate and contained higher phosphorus than the milks from the AYB
      flours. The fermented milk blend had higher protein, ash and sugar levels and
      lower phytate and stachyose levels compared to non-fermented blend. Raffinose was
      reduced to trace levels in the fermented milks. The milks were appetizing. The
      fermented milk blend was more acceptable than others and was preferred in terms
      of flavor and color. It had greater advantages over the other vegetable milks
      evaluated in terms of zinc, phosphorus and stachyose levels.

PMID- 9629867
TI  - Effect of cooking on cowpea protein fractions.
AB  - Nine cowpea cultivars obtained from Wad Medani Research Station were used in this
      study. The variation in protein fraction was: albumins 4.0-12.0, globulins 65.6
      79.7, prolamins 1.4-2.2, G1-glutelins 0.9-3.0, G2-glutelins 1.4-2.9, G3-glutenins
      9.1-14.0 and insoluble protein 0.5-3.0%. Two cowpea cultivars, H8-14 and CB-46,
      selected for their high albumin content, were cooked in 150 ml of boiling
      distilled water under reflux for 45 minutes. The protein fractions in the cooked
      seeds were determined. Results indicated that albumin and globulin fractions
      decreased significantly (p < or = 0.05) for both cultivars after cooking. This
      decrease was accompanied by a significant increase in G3-glutelin fractions.

PMID- 9629868
TI  - Psycho-oncology and supportive care: an interview with Darius Razavi.

PMID- 9629869
TI  - Oncology Home Care Service.
AB  - The Oncology Home Care Service in Basel provides nursing support to let cancer
      sufferers choose where they receive palliative care. Most of the cost is borne by
      the patient's health insurance.

PMID- 9629870
TI  - Neuropharmacology of emesis and its relevance to anti-emetic therapy. Consensus
      and controversies.
AB  - Recent great advances in the neuropharmacology of the emetic pathways have led to
      better therapy and improved insight into pathophysiological processes in patients
      undergoing chemo- and radiotherapy. This article gives an overview of the area,
      outlines current controversies and makes recommendations for future clinical
      studies.

PMID- 9629871
TI  - Corticosteroids, dopamine antagonists and other drugs.
AB  - The literature on corticosteroids, dopamine antagonists and other antiemetics,
      such as cannabinoids and benzodiazepines. was reviewed and presented at a
      consensus conference on antiemetics. Based on the reviews and the discussion
      during the conference, guidelines for the use of these agents are given.

PMID- 9629872
TI  - Optimal selection of antiemetics in children receiving cancer chemotherapy.
AB  - Only a few studies have been carried out specifically on the prevention of nausea
      and vomiting in children receiving chemotherapy. In these patients older
      antiemetic drugs such as metoclopramide and phenothiazines had moderate efficacy
      and induced significant side effects, especially marked sedation and
      extrapyramidal reactions. In comparative trials the 5-HT3 receptor antagonists
      have shown better efficacy and tolerability than chlorpromazine or metoclopramide
      combined with dexamethasone. The combination of a 5-HT3 receptor antagonist plus
      dexamethasone is superior to a 5-HT3 receptor antagonist alone and should be the
      standard antiemetic prophylaxis in all paediatric patients receiving highly or
      moderately emetogenic chemotherapy. The optimal dose and scheduling of these
      antiemetic drugs need to be studied, as well as the antiemetic efficacy, in the
      prevention of chemotherapy-induced delayed and anticipatory emesis in children.

PMID- 9629873
TI  - Methodology of antiemetic trials: response assessment, evaluation of new agents
      and definition of chemotherapy emetogenicity.
AB  - Establishing appropriate and practical methodology is a key to progress in the
      investigation of chemotherapy-induced nausea and vomiting. Critical issues
      include patient response assessment, proper trial design for evaluating new
      agents, and the definition of chemotherapy emetogenicity. In assessing antiemetic
      response, the primary end-point should be complete control of emesis and nausea.
      Emesis and nausea should be independently assessed with the period of observation
      defined (acute, delayed, anticipatory). Emesis can be evaluated by measuring the
      number of emetic episodes either by direct observation or by patient self-report
      using patient-completed diaries. Nausea should be measured by patient self-report
      with the standard parameters, including frequency and intensity. New antiemetic
      drug development should proceed in an orderly progression from open-label phase I
      II trials defining tolerance and minimally fully effective dose to phase III
      comparative trials. A randomized, parallel, double-blind study is the preferred
      design for the latter, and the comparator arm should always include the current
      best available treatment. Antiemetic placebos are no longer acceptable with
      chemotherapy regimens known to produce emesis in a majority of patients. None of
      the emetogenic classifications proposed to date adequately accounts for all known
      important patient- and treatment-related prognostic variables. A modification of
      a recently reported schema is proposed for use in making antiemetic treatment
      recommendations and defining the emetogenic challenge in clinical trials.

PMID- 9629874
TI  - Delayed emesis following anticancer chemotherapy.
AB  - Delayed emesis is a distinct syndrome where vomiting begins or persists 24 or
      more hours after chemotherapy. It is more likely to occur when the stimulus for
      emesis is strong and/or acute vomiting is poorly controlled. The pathophysiology
      appears different than that which causes acute emesis. The literature reporting
      clinical trials to prevent delayed nausea and vomiting are presented. The best
      ways of preventing delayed emesis following anticancer chemotherapy are
      discussed.

PMID- 9629875
TI  - Antiemetic strategies for high-dose chemoradiotherapy-induced nausea and
      vomiting.
AB  - The treatment of nausea and vomiting in patients receiving high doses of
      irradiation and/or chemotherapeutic agents as preparation for hematopoietic stem
      cell transplantation is discussed. Such patients have very high rates of both
      early and delayed emesis. Based on the available evidence it is recommended that
      5-HT3 receptor antagonists be used to combat emesis in this setting. Continued
      research is also required to define the optimal antiemetic strategy for these
      patients.

PMID- 9629876
TI  - Consensus proposal for 5HT3 antagonists in the prevention of acute emesis related
      to highly emetogenic chemotherapy. Dose, schedule, and route of administration.
AB  - Selective antagonists to the Type 3 serotonin receptor (5HT3) in combination with
      corticosteroids are now considered the standard of care for the prevention of
      emesis from moderately to highly emetogenic chemotherapy. Here we address issues
      of optimal dose, schedule and route of administration of four currently available
      selectable 5HT3 antagonists. This paper utilizes an evidence based medicine
      approach to the literature regarding this class of drugs, emphasizing the results
      large, randomized, controlled trials to make formal recommendations concerning
      optimal use of this important new class of anti-emetic agents. We conclude that
      for each drug there is a plateau in therapeutic efficacy at a definable dose
      level above which further dose escalation does not improve outcome. Furthermore,
      a single dose is as effective as multiple doses or continuous infusion, and
      finally, emerging data demonstrate that the oral route is equally efficacious as
      the intravenous route of administration, even with highly emetogenic
      chemotherapy.

PMID- 9629877
TI  - Anticipatory nausea and vomiting in the era of 5-HT3 antiemetics.
AB  - Cancer chemotherapy is known to lead to nausea and vomiting in a large proportion
      of cases. If emesis is severe it can lead in its turn to anticipatory nausea and
      vomiting (ANV), which cannot be controlled by antiemetic medication. The etiology
      of ANV and various methods that have been used to counteract the condition are
      discussed.

PMID- 9629878
TI  - Consensus regarding multiple day and rescue antiemetic therapy.
AB  - Different forms of moderately and highly emetogenic cancer chemotherapy that are
      administered over several days per cycle are discussed with reference to the most
      efficacious antiemetic therapy. Both preventive and rescue antiemetic therapy are
      considered.

PMID- 9629880
TI  - Statistical considerations in the design, conduct and analyses of antiemetic
      clinical trials. An emerging consensus.
AB  - Various aspects of trial design and planning for clinical testing of antiemetic
      therapies administered to cancer patients are considered. It is generally felt
      that a randomized double-blind parallel-arm design is the best. Ways of achieving
      adequate power of such studies are discussed briefly, as is the need for previous
      identification of primary and secondary end-points. Finally, summary
      recommendations are given.

PMID- 9629879
TI  - Aetiology and prevention of emesis induced by radiotherapy.
AB  - The introduction of new antiemetics has resulted in renewed interest in the
      aetiology and control of radiation induced emesis. Studies both with fractionated
      treatment and with high-dose single exposures have clearly demonstrated the value
      of the 5HT3 receptor antagonist antiemetics. This paper reviews the selection of
      optimal antiemetics.

PMID- 9629881
TI  - Palliative care of cancer patients: audit of current hospital procedures.
AB  - The palliative care of cancer patients admitted for tumour-related symptoms to
      three different departments (medical oncology, radiotherapy, internal medicine)
      of a general hospital was prospectively audited. The physicians directly
      responsible for the patients provided prospective data by reporting both the
      diagnostic and therapeutic interventions performed and the degree of control
      achieved for each symptom. A patient form for evaluation of the control achieved
      in the case of each symptom by means of linear analogue scales was also provided.
      The appropriateness of all procedures was evaluated by two external auditors.
      Over 6 months, 125 such admissions were recorded: 24 patients entered the study
      and the management of 56 symptoms, the most common of which were pain and
      dyspnoea, was reviewed. A total of 72 diagnostic procedures were performed,
      deemed necessary for only 50% of symptoms, optional for 15%, and performed as
      part of a logical sequence for 38%. A total of 130 therapeutic interventions were
      undertaken, deemed necessary for 55% of symptoms, optional for 15% and carried
      out as part of a logical sequence for 44%. Re-evaluations of symptoms and
      physician and patient evaluations of the degree of control achieved could not be
      assessed because of lack of information. The audit could not be repeated owing to
      the low accrual of patients and incompleteness of the data collection. Reasons
      for failure of the study and proposals for feasible methods of auditing the
      management of symptoms in cancer patients are discussed.

PMID- 9629882
TI  - Prospective study of bacteraemia in cancer patients. Results of a French
      multicentre study.
AB  - We performed a prospective assessment of the current epidemiology of bacteraemia
      in cancer patients hospitalized in 70 different adult and paediatric haematology
      and oncology departments. Over a 1-month period, microbiologists from 54
      hospitals collected clinical data relating to patients with at least one positive
      blood culture. In addition, all strains isolated were assessed for their in vitro
      susceptibility to three broad-spectrum cephalosporins suitable for empirical
      treatment in cancer patients: cefpirome, cefepime and ceftazidime. A total of 494
      different strains were isolated from 1,038 blood cultures taken from 403
      different patients. Seventeen strains were isolated from 13 patients with various
      nonmalignant diseases, and these cases were excluded from analysis. Overall, 330
      (69.2%) of the strains were isolated in patients with haematological malignancy
      and 147 (30.8%), in patients with solid tumours. There was no difference in the
      distribution of the species involved in bacteraemia between patients with
      haematological malignancy and patients with solid tumours: coagulase-negative
      staphylococci were the leading pathogens (50.6% and 44.9%, respectively),
      followed by E. coli (11.2% and 12.2% respectively), S. aureus (6.3% vs 7.5%),
      streptococci (4.8% vs 5.4%) and P. aeruginosa (5.2% vs 4.8%). All other species
      accounted for less than 5% in both groups. There was no difference in the strain
      distribution with age (> or = 15 years vs < 15 years) or type of underlying
      disease. S. aureus and Enterobacteriaceae bacteraemia were more frequent in
      patients with end-stage disease, while oral streptococci, Enterobacteriaceae and
      P. aeruginosa infections were more frequent in patients who were severely
      neutropenic. Digestive tract decontamination was associated with increased
      frequency of oral streptococci and decreased frequency of Enterobacteriaceae
      infections. All three cephalosporins demonstrated similar activity against E.
      coli, while cefpirome and cefepime appeared to be more effective against other
      Enterobacteriaceae. Ceftazidime had better activity against P. aeruginosa.
      Cefpirome was the most effective against Gram-positive cocci, especially oral
      streptococci and methicillin-susceptible staphylococci.

PMID- 9629883
TI  - Predictive factors for psychological distress in ambulatory lung cancer patients.
AB  - Although there is a need for systematic research on the psychosocial issues faced
      by lung cancer patients, there have been few studies in this area. The objective
      of the present study was to investigate potential predictors of psychological
      distress among ambulatory lung cancer patients. The variables examined included
      the patients' characteristics, coping responses, and social support factors. Lung
      cancer patients completed the Profile of Mood States (POMS) and the Mental
      Adjustment to Cancer scale (MAC scale), and information pertaining to demographic
      variables and social support factors was obtained from them at a structured
      interview. Evaluable data were obtained from 87 patients. The results of multiple
      regression analysis indicated that female gender, living alone, no children in
      the role of confidant, nurses as confidants, and helplessness/hopelessness as a
      coping style were predictive for psychological distress. Information on patients'
      demographic variables and psychosocial correlates of psychological distress may
      later be useful in developing interventions to facilitate their adjustment to
      lung cancer.

PMID- 9629884
TI  - The antiemetic efficacy of granisetron plus dexamethasone, haloperidol and
      loracepam in breast cancer patients treated with high-dose chemotherapy with
      peripheral blood stem-cell support.
AB  - There has recently been a marked trend to increasing dose intensity in cancer
      chemotherapy, with or without peripheral blood stem-cell support, which has been
      associated with a higher frequency of nausea and vomiting. Antiemetic treatment
      in this setting has not been extensively analysed. From October 1995 to January
      1997, prevention of emesis with granisetron 3 mg/12 h i.v., dexamethasone 12
      mg/24 h i.v., haloperidol 0.5 mg/12 h p.o., and loracepam I mg/24 h p.o. was
      instituted in 30 breast cancer patients treated with high-dose chemotherapy (a 4
      day intravenous continuous infusion of cyclophosphamide 1500 mg/m2 per day, thio
      TEPA 125 mg/m2 per day and carboplatin 200 mg/m2 per day).A total of 30% of the
      patients (9/30) obtained complete or major protection on the 4 days of
      chemotherapy treatment (96.7% (29/30) on day 1, 86.7% (26/30) on day 2, 70%
      (21/30) on day 3, and 50% (15/30) on day 4). On the days following chemotherapy,
      46.7% (14/30) presented fewer than two emetic episodes on day 5, 70% (21/30) on
      day 6, 83.4% (25/30) on day 7 and, 93.3% (28/30) on day 8. This energic
      antiemetic combination treatment has hardly any effect in the prevention of
      emesis, providing complete or major protection of 30% for the 4 days of
      chemotherapy treatment. Further investigation aimed at improving antiemetic
      treatment results is necessary.

PMID- 9629885
TI  - Predictors of mortality in bacteremic cancer patients: retrospective analysis of
      64 deaths occurring among 262 bacteremic episodes.
AB  - A total of 262 bacteremic episodes were observed in cancer patients in a single
      cancer institution during the last 7 years, and the recorded outcome was death in
      65. The 65 patients who died (24.8% overall mortality) were divided
      retrospectively into two subgroups: (a) those who died of underlying disease with
      bacteremia (45 cases, 16.9% crude mortality) and (b) those who died of bacteremia
      (20 patients, 7.7% attributable mortality). Comparison of several risk factors in
      subgroups of patients who achieved a cure (197 cases) and of those who died and
      whose deaths were attributable (20 cases) revealed six risk factors that were
      associated with attributable mortality: (1) chemotherapy-induced neutropenia (P <
      0.03), (2) Acinetobacter/Stenotrophomonas spp. bacteremias (P < 0.001), (3) liver
      failure (P < 0.001), (4) inappropriate therapy (P < 0.0001), (5) organ
      complications (P < 0.003) and (6) multiresistant organisms (P < 0.001).
      Enterococci and Pseudomonas aeruginosa, surprisingly, were found more frequently
      in those who died of an underlying disease with bacteremia than among patients
      who were cured (17.6% vs 7.6%, P < 0.05 and 29.1% vs 13.8%, P < 0.02). Those who
      died of infection had higher numbers of positive blood cultures, with 2.05 per
      episode, than did those who died of underlying disease with bacteremia (1.82) or
      those who were cured (1.51). Other risk factors, such as underlying disease, type
      of chemotherapy, origin of bacteremia, age, and catheters did not predict either
      overall or attributable mortality within the study group.

PMID- 9629887
TI  - Prevention of Pneumocystis carinii pneumonia with cotrimoxazole 18 mg/kg.

PMID- 9629886
TI  - Epicutaneous breast forms. A new system promises to improve body image after
      mastectomy.
AB  - Mastectomies will remain a treatment alternative for breast cancer in spite of
      efforts to perform more breast-conserving treatment. Restoration of body symmetry
      may then be an important issue, which can be achieved by surgical breast
      reconstruction or with an epicutaneous breast prosthesis. A new improved system
      has recently been developed, which is self-adhesive to the thorax wall. In this
      study we investigated the advantages and disadvantages of the new system. The
      body image of 55 patients after unilateral mastectomy was assessed before they
      entered the study and after approximately 6 months of experience with the system.
      The "Frankfurter Korperkonzeptskalen" plus additional questions concerning
      problems after mastectomy and the handling of the new breast form were used for
      the assessment. About 50% of the patients had problems with the adhesiveness of
      the breast form, which remains a problem to be solved. Patients who suffered
      badly from mastectomy, have a smooth and plane mastectomy scar, and who were not
      suffering from hot flushes, which can impair the adhesiveness of the prosthesis,
      were more likely to profit from the new self-supporting breast forms. Significant
      differences were observed in the scales "self-acceptance of the body", acceptance
      of the body by others" for the subsets of patients mentioned above. The
      differences were less pronounced in patients who were already familiar with
      another type of epicutaneous breast form, which is attached to an adhesive plate
      on the thorax wall by nylon touch and close fasteners. Most (90.7%) of the
      patients would recommend this new type of breast prosthesis for other patients
      with mastectomy. The concept of self-supporting breast forms is an improvement
      with respect to social and psychological rehabilitation. According to the
      manufacturer, the problem with adhesion has meanwhile been solved.

PMID- 9629888
TI  - The gel edge electric field gradients in denaturing polyacrylamide gel
      electrophoresis.
AB  - It has previously been shown that zones of higher electric field form close to
      the loading end of the gel during denaturing polyacrylamide gel electrophoresis.
      Here we show that the field can reach up to three times its normal mean value a
      few cm in front of the loading wells when 44.5 mM Tris-44.5 mM boric acid-1 mM
      EDTA is used as the gel buffer. We also demonstrate that this electric field
      gradient is mostly due to the difference in ion transference numbers at the
      gel/buffer interface caused by the high viscosity of the urea solution contained
      in the gel. This field gradient leads to increased band widths and forces us to
      redefine both the electrophoretic mobility and the mean field intensity. We
      discuss some methods that can be used to minimize the effects of this gradient.

PMID- 9629889
TI  - Do DNA gel electrophoretic mobilities extrapolate to the free-solution mobility
      of DNA at zero gel concentration?
AB  - The electrophoresis of small DNA fragments has been measured in dilute agarose
      and polyacrylamide gels cast and run in Tris-acetate-EDTA (TAE) and Tris-borate
      EDTA (TBE) buffers. Ferguson plots were constructed to extrapolate the mobilities
      to zero gel concentration and estimate the free solution mobility of DNA. In
      polyacrylamide gels, in both TAE and TBE buffers, the extrapolated mobilities at
      zero gel concentration increased gradually with decreasing DNA molecular weight,
      went through a maximum at approximately 60 bp, and then decreased again. The
      increase in the extrapolated mobilities with decreasing molecular weight observed
      for DNA fragments > or = 60 bp can be attributed to transient interactions
      between the migrating DNA molecules and the polyacrylamide gel fibers. If such
      interactions are eliminated by extrapolating the mobilities to both zero gel
      concentration and zero DNA molecular weight, the apparent free solution mobility
      of DNA is found to be 3.1 x 10(-4) cm2 V(-1) s(-1) in TAE buffer and 4.2 x 10(-4)
      cm2 V(-1) s(-1) in TBE buffer at 20 degrees C, reasonably close to the actual
      free solution mobilities measured in the same two buffers by capillary
      electrophoresis (N. C. Stellwagen et al., Biopolymers 1997, 42, 687-703). The
      significantly larger electrophoretic mobility observed in TBE buffer is most
      likely due to the formation of nonspecific, highly charged deoxyribose-borate
      complexes in this buffer medium. For DNA molecules < or = 60 bp in size, the
      decrease in the extrapolated mobilities with decreasing molecular weight
      parallels the decrease in their free solution mobilities observed by capillary
      electrophoresis. In agarose gels, the extrapolated mobilities of small DNA
      molecules at zero gel concentration appear to be independent of molecular weight.
      The apparent free solution mobilities are found to be (3.0 +/- 0.1) x 10(-4) cm2
      V(-1) s(-1) in TAE buffer and (3.2 +/- 0.1) x 10(-4) cm2 V(-1) s(-1) in TBE
      buffer. The very similar mobilities observed in the two buffer media suggest that
      the borate ions in TBE buffer primarily form complexes with the galactose
      residues in the agarose gel fibers, rather than with the migrating DNA molecules,
      because of mass action effects. The formation of borate-agarose complexes,
      increasing the net negative charge of the agarose gel fibers, appears to be
      responsible for the markedly increased electroendosmotic flow observed in agarose
      gels cast and run in TBE buffer (N. C. Stellwagen, Electrophoresis 1992, 13, 601
      603).

PMID- 9629890
TI  - Enhanced hybridization labeling signals in Southern blotted DNAs fractionated
      with voltage gradient gel electrophoresis.
AB  - An enhancement of hybridization labeling signals is demonstrated in Southern
      blotted DNAs, fractionated by voltage gradient gel electrophoresis. This
      enhancement is due to a reduced thickness of each single nucleic acid band in the
      gel as a consequence of the gradient effect, corresponding to an increased
      concentration of DNA per unit area.

PMID- 9629891
TI  - Large scale isolation of genes as DNA fragment lengths by continuous elution
      electrophoresis through an agarose matrix.
AB  - A simple procedure for the isolation of genes as DNA fragment lengths is
      described. By using a commercial continuous elution protein electrophoresis
      apparatus and incorporating an agarose matrix, preparative scale amounts (300
      microg) of DNA can be purified by fragment lengths from a mixture of genomic
      fragment lengths with high recovery yields. Fractions corresponding to unique
      fragment length ranges are screened for individual genes by dot-blot analysis.
      Using this technique, we have isolated two genes: PGK1, a single copy
      housekeeping gene; and p53 (exons 3-11), a tumor suppressor gene, whose DNA
      fragment lengths elute at 4 and 7.5 kbp, respectively, from a single preparative
      run. As an example of the utility of the technique, we applied it to improving
      the sensitivity of the ligation-mediated polymerase chain reaction (LMPCR)--a
      nucleic acid amplification technique used for the detection and mapping of DNA
      damage along genes. By eliminating excess nontargeted genomic DNA, the agarose
      matrix continuous elution electrophoresis (CEE) procedure provided a 24-fold
      increase in signal strength attributable to base damage caused by exposing DNA to
      reactive oxygen species. Genomic DNA fragment length purification by agarose
      matrix CEE should also prove useful in other research areas requiring gene
      isolation, such as genomics and molecular biology.

PMID- 9629892
TI  - Detection of clonal T cells in cutaneous T cell lymphoma by polymerase chain
      reaction: comparison of mutation detection enhancement-polyacrylamide gel
      electrophoresis, temperature gradient gel electrophoresis and fragment analysis
      of sequencing gels.
AB  - Cutaneous T cell lymphomas (CTCL) can be differentiated from benign inflammatory
      dermatoses by the demonstration of clonal T cells in skin biopsy. As a marker of
      the T cell clonality, the rearrangement of the T cell receptor (TCR) genes is
      amplified by polymerase chain reaction (PCR) and subsequently analyzed by several
      electrophoresis techniques. Since the validity of this approach depends
      substantially on the separating capacity of the applied electrophoresis
      technique, we investigated in the present study the lower detection limit and the
      sensitivity of heteroduplex-loaded polyacrylamide gel electrophoresis on MDE
      (mutation detection enhancement) gels (HD-MDE PAGE), of heteroduplex-loaded
      temperature gradient gel electrophoresis (HD-TGGE) and fragment analysis (FA) on
      sequencing gels. Genomic DNA from formalin-fixed, paraffin-embedded skin biopsies
      of 53 CTCL specimens and 27 samples of benign dermatoses was analyzed by TCRy PCR
      followed by electrophoretic separation. Clonality was detected by HD-MDE PAGE in
      22, by HD-TGGE in 34, and by FA in 33 of the 53 CTCL cases. Additionally, FA
      revealed an oligoclonal fragment profile in seven CTCL specimens. In the 27
      samples from benign dermatoses, HD-MDE PAGE and HD-TGGE showed the expected
      polyclonal pattern in 26, and FA in 25 specimens. HD-TGGE and FA detected a
      clonal pattern down to a dilution of 10(3) monoclonal cells in 10(6) peripheral
      blood mononuclear cells (PBMC), while HD-MDE PAGE revealed a detection limit of
      10(4) monoclonal cells in 10(6) PBMC. In conclusion, HD-TGGE and FA possess a
      higher sensitivity and lower detection limit than HD-MDE PAGE. Therefore, both
      former techniques are useful tools for the routine diagnostic procedure. With
      regard to time and cost, we recommend HD-TGGE.

PMID- 9629893
TI  - Simultaneous genotyping of alcohol dehydrogenase 2 (ADH2) and aldehyde
      dehydrogenase 2 (ALDH2) loci by amplified product length polymorphism (APLP)
      analysis.
AB  - Genotyping of the alcohol dehydrogenase 2 (ADH2) and aldehyde dehydrogenase 2
      (ALDH2) loci is important in alcohol studies. We describe a method for
      simultaneous genotyping of ADH2 and ALDH2 based on amplified product length
      polymorphism (APLP) analysis. Two polymerase chain reaction (PCR) fragments for
      ADH2 (57 bp, 53 bp) and two for ALDH2 (78 bp, 73 bp) are simultaneously
      amplified. Nine banding patterns reflecting the genotypes of the ADH2 and ALDH2
      loci are clearly and unambiguously distinguished. The APLP method seems to be
      particularly suited for large-scale population studies of ADH2 and ALDH2 loci
      because it is simple and rapid.

PMID- 9629894
TI  - Population analysis of the collagen type IIalpha1 3' variable number of tandem
      repeat polymorphism by heteroduplex genotyping.
AB  - The AT-rich variable number of tandem repeat (VNTR) marker at the 3' end of the
      collagen type IIalpha1 (COL2A1) gene has been shown to have a complex structure
      with extensive sequence variations among repeat units. We analyzed this VNTR
      polymorphism in a large population of 972 Caucasian individuals with a genotyping
      procedure involving heteroduplex analysis of PCR products using polyacrylamide
      gel electrophoresis. Seven size alleles were identified, combining to 19
      different homoduplex genotypes (heterozygosity = 0.64). These could be further
      dissected by analysis of heteroduplexes into 85 different heteroduplex genotypes
      (heterozygosity = 0.84). By systematically heteroduplexing homozygous and
      heterozygous individuals in vitro, characteristic heteroduplex doublet bands were
      generated of known allelic composition. A comparison of these doublets with
      heteroduplex patterns observed in the population allowed us to identify 29
      alleles. The degree of correspondence with a different COL2A1 VNTR genotyping
      system, based on size separation of single-strand VNTR alleles [1], was
      investigated by the analysis of samples typed with both methods, including
      samples from reference CEPH pedigrees. This revealed improved genetic resolution
      by the heteroduplex method including discrimination of frequent alleles
      considered identical by the single-strand analysis. Our findings demonstrate
      heteroduplex analysis of the COL2A1 VNTR to be a robust and highly informative
      genetic marker system. The documented increased genetic variability has important
      implications in forensic and paternity testing, as well as in linkage and
      association studies relating genetic variation at this locus to disease
      endpoints.

PMID- 9629895
TI  - Screening of a highly polymorphic microsatellite for microheterogeneity in human
      identification.
AB  - Single-strand conformation polymorphism (SSCP) analysis combined with automated
      laser fluorescence detection is proposed as a comprehensive, rapid and sensitive
      method for screening sequence variation of the human beta-actin-related
      pseudogene (HUMACTBP2). Eleven sequenced alleles representing each type of known
      sequence variant of HUMACTBP2 locus were studied. Allelic variants of the same
      size but different sequence structures are easily resolved on the basis of their
      secondary conformation. Fifty ACTBP2 amplification products previously typed on a
      denaturing gel were repeatedly examined to determine the utility of SSCP analysis
      in terms of ease of interpretation and reproduction capabilities of the
      conformational patterns. Eleven sequenced ACTBP2 allelic variants were used as
      external conformation standards in polymerase chain reaction (PCR)-SSCP
      subtyping. This enabled identification of polymorphism in a particular length
      variant and therefore consistent discrimination between heterozygous samples
      appeared identical on denaturing gels. Of five "homozygous" samples, one was
      shown to be heterozygous for two distinct alleles of the same size but different
      sequences. Thus, the method provides a unique possibility for detecting false
      homozygotes. The technique complements both denaturing gel electrophoresis and
      DNA sequencing in studies on the overall variability of the ACTBP2 locus.

PMID- 9629896
TI  - Detection of sequence variation in parasite ribosomal DNA by electrophoresis in
      agarose gels supplemented with a DNA-intercalating agent.
AB  - This study evaluated the use of a commercially available DNA intercalating agent
      (Resolver Gold) in agarose gels for the direct detection of sequence variation in
      ribosomal DNA (rDNA). This agent binds preferentially to AT sequence motifs in
      DNA. Regions of nuclear rDNA, known to provide genetic markers for the
      identification of species of parasitic ascarid nematodes (order Ascaridida), were
      amplified by polymerase chain reaction (PCR) and subjected to electrophoresis in
      standard agarose gels versus gels supplemented with Resolver Gold. Individual
      taxa examined could not be distinguished reliably based on the size of their
      amplicons in standard agarose gels, whereas they could be readily delineated
      based on mobility using Resolver Gold-supplemented gels. The latter was achieved
      because of differences (approximately 0.1-8.2%) in the AT content of the
      fragments among different taxa, which were associated with significant
      interspecific differences (approximately 11-39%) in the rDNA sequences employed.
      There was a tendency for fragments with higher AT content to migrate slower in
      supplemented agarose gels compared with those of lower AT content. The results
      indicate the usefulness of this electrophoretic approach to rapidly screen for
      sequence variability within or among PCR-amplified rDNA fragments of similar
      sizes but differing AT contents. Although evaluated on rDNA of parasites, the
      approach has potential to be applied to a range of genes of different groups of
      infectious organisms.

PMID- 9629897
TI  - Preparative isoelectric focusing and preparative electrophoresis of hydrophobic
      Candida albicans cell wall proteins with in-line transfer to polyvinylidene
      difluoride membranes for sequencing.
AB  - Hydrophobic proteins in the cell wall of the opportunistic fungal pathogen
      Candida albicans are involved in adhesion of this organism to host tissue and
      thus play a role in its pathogenicity. The hydrophobic nature of these proteins
      results in their loss during purification due to adsorption to apparatus
      surfaces. This problem, combined with their low abundance, has made it
      problematic to purify the hydrophobic proteins in sufficient quantity for
      sequencing or biochemical analysis. We describe a system that combines
      preparative isoelectric focusing with continuous elution preparative
      electrophoresis. The system provides a two-dimensional protein separation while
      maintaining protein solubility and minimizing protein loss due to adsorption. In
      addition, we have added an in-line transfer of electrophoretic fractions directly
      to polyvinylidene difluoride (PVDF) membranes, which further reduces both
      exposure to apparatus surfaces and purification time.

PMID- 9629898
TI  - Electrophoresis-related protein modification: alkylation of carboxy residues
      revealed by mass spectrometry.
AB  - In recent years, the combination of gel electrophoresis and mass spectrometry has
      developed into one of the most powerful approaches for the analysis of proteins.
      However, a number of gel electrophoresis-induced protein modifications have been
      described. Cysteine is the most endangered amino acid readily reacting with
      mercaptoethanol or free acrylamide. In the course of studies on glucan
      phosphorylases (E.C.2.4.1.1) from white potato (Solanum tuberosum L.) and the T
      cell receptor, we noticed that proteolytic peptides from these proteins can
      undergo an unexpected modification, giving rise to a mass increment of 14 Da. By
      post-source decay (PSD) analysis the modification was identified as methylation
      of the glutamic acid side chain carboxyl group. The methylation takes place
      during Coomassie blue staining of proteins if both trichloroacetic acid and
      methanol are present in the staining solution. Replacement of methanol by ethanol
      under otherwise unchanged conditions results in ethylation of the peptides. The
      in vitro alkylation was further studied by using synthetic peptides which
      contain, at different positions: glutamic acid, aspartic acid or the
      corresponding amides. The kinetic analysis of the observed reactions revealed
      that glutamic acid is preferentially methylated. The three other amino acid
      residues can be methylated but with a velocity at least one order of magnitude
      lower. Although these modifications complicate the interpretation of the spectra,
      they provide valuable structural information.

PMID- 9629899
TI  - Affinity isoelectric focusing of human serum apolipoprotein B-containing
      lipoproteins on agarose gels with cyclodextrins.
AB  - In an attempt to subfractionate apolipoprotein B-containing lipoproteins (apoB
      Lp), agarose isoelectric focusing (IEF) of apoB-Lp in human sera was carried out
      in the presence of two kinds of cyclodextrins (CDs), which have different
      affinities for cholesterol. ApoB-Lp in the agarose gels was detected by
      immunofixation, followed by protein staining. In the presence of both 11.4 mg/mL
      alpha-CD and 3.51 mg/mL beta-CD, but not either one alone, IEF separated a
      maximum of six apoB-Lp bands. Electrophoresis failed to separate the apoB-Lp
      subfractions under similar conditions with CDs. The patterns of apoB-Lp in IEF
      with the CDs appeared to differ in some sera. Since the subfractions of apoB-Lp
      can be separated without ultracentrifugation of serum, the present method serves
      for the screening of apoB-Lp heterogeneity on native serum lipoproteins.

PMID- 9629900
TI  - Activity staining of pectinesterase on polyacrylamide gels after acidic or sodium
      dodecyl sulfate electrophoresis.
AB  - Pectinesterase (PE), from commercial orange peels or ammonium sulfate
      fractionation (50-80% saturation) of pea pods, was detected on polyacrylamide
      gels after native acidic polyacrylamide gel electrophoresis (PAGE) or sodium
      dodecyl sulfate (SDS)-PAGE by using the synthetic substrate beta-naphthyl acetate
      (beta-NA). The release of beta-naphthol (at 322 nm) from beta-NA was proportional
      to PE activity. The PE activity bands on polyacrylamide gels after native acidic
      PAGE or SDS-PAGE were stained with a combination of tetrazotized o-dianisidine
      and beta-NA. This fast and sensitive method can be used for enzyme purification
      and characterization.

PMID- 9629901
TI  - DNA cycle sequencing of a common restriction fragment of Staphylococcus aureus
      bacteriophages by capillary electrophoresis using replaceable linear
      polyacrylamide.
AB  - The nucleotide sequence of a part of a 4.9 kbp common restriction fragment
      isolated from Staphylococcus aureus bacteriophage (bacterial virus) 3A has been
      determined by capillary electrophoresis (CE). The fast separation of sequencing
      fragments in linear polyacrylamide solution at a temperature of 55 degrees C
      allowed the reading of more than 650 bases of sequence in 60 min. The single
      strand (ss)DNA fragments were prepared by cycle sequencing with fluorescently
      labeled dideoxy-terminators on the cloned bacteriophage DNA template. With
      respect to analysis speed, sequence read-length, low sample consumption and
      automation, CE offers a simple, labor-saving and inexpensive procedure for DNA
      sequencing. Operating the CE columns at elevated temperature proved to be a rapid
      procedure capable of extending sequence read-length. The resulting sequence of
      the common restriction fragment can be used for the preparation of specific
      primers and oligonucleotide hybridization probes for identification of
      Staphylococcus aureus bacteriophages and/or prophages belonging to the
      bacteriophage species 3A.

PMID- 9629902
TI  - "Schizophrenic" behavior of zones in capillary zone electrophoresis: explanation
      of an old problem.
AB  - Background electrolyte (BGE) systems with two coions are frequently used in
      capillary zone electrophoresis (CZE), especially in cases where indirect optical
      detection is employed. This study investigates the behavior of analytes, which
      possess mobilities intermediate to those of the BGE coions used. Besides the
      expected behavior, where the analytes provide either tailing or fronting zones,
      unusual behavior with extraordinary zone broadening is also observed in some
      cases. The explanation for this effect is that binary BGE systems involve, as a
      physico-chemical rule, a region where the analytes are forced by one coion to
      give tailing zones and simultaneously by the other coion to give fronting zones.
      The result of this "schizophrenic" situation is extraordinary zone broadening and
      deterioration of the detection record. A series of experiments is presented
      showing in a telling way the electromigration behavior of the discussed type of
      zones as well as the ways to remedy the deterioration of the peak shape by a mere
      slight changing of the quantitative composition of the BGE used.

PMID- 9629903
TI  - Detectability improvements in capillary zone electrophoresis by combining single
      capillary isotachophoretic preconcentration and frequency doubled argon ion laser
      induced fluorescence detection.
AB  - Due to the small path length and low injection volume the concentration limit of
      detection is comparatively poor in capillary electrophoresis (CZE) with UV
      detection. This limitation can be overcome by means of preconcentration methods
      and/or improved detection techniques. This paper describes a strategy where
      isotachophoresis (ITP) is used to preconcentrate a new cholinesterase inhibitor
      (NXX-066) prior to a capillary zone electrophoresis analysis in the same single
      capillary. A hydrodynamic backpressure is used to prevent the analyte from
      migrating out of the capillary. Laser-induced fluorescence (LIF) is used to
      further increase the detectability. The total gain in detectability with ITP-CZE
      LIF compared to CZE-UV was at least 5500-fold, and it is possible to determine
      NXX-066 at the 1 nM level. The ITP-CZE method was further evaluated for two beta
      blockers; the mean coefficient of variation of the peak areas was 3.4% and the
      linearity of the calibration plots was satisfying.

PMID- 9629904
TI  - Enhanced separation of antidepressant drugs using a polymerized nonionic
      surfactant as a transient capillary coating.
AB  - The separation of seven structurally similar antidepressant drugs (amitriptyline,
      nortriptyline, imipramine, desipramine, protriptyline, doxepin, and nordoxepin)
      was achieved in under 15 min using a novel nonionic micelle polymer, poly(n
      undecyl-alpha-D-glucopyranoside) (PUG) by use of capillary zone electrophoresis
      (CZE). Systematic studies with varying polymer concentration, pH, and percent
      organic modifier were conducted in order to find the optimum conditions for
      baseline separation of the seven tricyclic antidepressants. In addition,
      equations for capacity factor were used to estimate the extent of what was
      initially thought to be micelle analyte interaction. A series of calculations
      show that a modified CZE system (PUG-CZE) was the actual mode of separation.
      Thus, our study concluded that PUG functioned in a non-electrokinetic
      chromatography mode.

PMID- 9629905
TI  - Population genetic study of four short tandem repeat loci in the Belgian
      population, using capillary electrophoresis.
AB  - Allele frequencies of four short tandem repeat loci (HumCD4, HumTH01, HumD21S11
      and HumSE33) were investigated in a sample of 395 unrelated Belgian individuals
      using multiplex polymerase chain reaction and capillary electrophoresis.
      Automated laser fluorescence was used to detect four fluorescent dyes, enabling
      the use of an internal standard within each lane. With this method rapid typing
      with high resolution was obtained and the different alleles were grouped on a
      statistical base. All loci meet Hardy-Weinberg expectations. The allelic
      frequency data, together with the constructed allelic ladder, can be used in
      paternity testing and personal identification in the medical and forensic
      sciences.

PMID- 9629906
TI  - Mixed-mode separation of polycyclic aromatic hydrocarbons (PAHs) in
      electrokinetic chromatography.
AB  - A mixed-mode separation technique has been developed and optimized for the
      separation of the 16 Environmental Protection Agency (EPA) priority polycyclic
      aromatic hydrocarbons (PAHs). The procedure utilized two different buffer
      additives as pseudo-stationary phases with different selectivities towards the
      analytes. Sodium dioctyl sulfosuccinate (DOSS) displayed selectivities for PAHs
      which were somewhat similar to the C18 phase in reversed-phase high performance
      liquid chromatography (HPLC). High acetonitrile content required for an effective
      separation prevented the formation of micelles as confirmed by fluorescence
      spectroscopy. Consequently, the separation could be attributed to the solvophobic
      association of the PAH molecules with hydrophobic chains of the DOSS surfactant.
      In another mode of separation, sulfobutylether-beta-cyclodextrin (SB-beta-CD)
      separated the 16 PAHs on the formation of inclusion complexes with the PAHs, and
      exhibited different selectivities for the PAHs compared to DOSS. SB-beta-CD and
      DOSS were then combined in the running buffer to form a mixed pseudo-stationary
      phase for the separation of the 16 PAHs. Due to the different selectivities of SB
      beta-CD and DOSS for the PAHs, the separation of the 16 PAHs was appreciably
      improved compared to that using DOSS or SB-beta-CD alone. All the 16 PAHs were
      baseline-resolved using an optimized running buffer containing 22.5 mM DOSS, 15
      mM SB-beta-CD, 15% acetonitrile and 5 mM hydroxypropyl-beta-cyclodextrin in 6 mM
      borate at pH 9.

PMID- 9629907
TI  - Enantioseparation of anaesthetic drugs by capillary zone electrophoresis using
      cyclodextrin-containing background electrolytes.
AB  - The enantiomers of five racemic anaesthetic drugs were resolved with
      cyclodextrins using capillary zone electrophoresis. Parameters which affected the
      chiral resolution, such as type and concentration of cyclodextrin, temperature,
      and addition of organic modifier were investigated. The results show that the
      enantiomeric discrimination of the solutes is influenced by the structural shape
      of the solute molecules, separation temperature, and type of cyclodextrin. It was
      found that alpha-cyclodextrin was the best enantioselector for resolution of
      prilocaine and ketamine, while the enantiomers of mepivacaine, ropivacaine, and
      bupivacaine were resolved with beta-cyclodextrin and/or modified beta
      cyclodextrins, i.e., methyl- and 2-hydroxypropyl-beta-cyclodextrin, as chiral
      selectors. The length of the alkyl chain on the amino group of the drug molecule
      had a strong effect on the enantioresolution of mepivacaine, ropivacaine, and
      bupivacaine. Baseline separation of racemic ketamine was achieved with alpha- and
      methyl-beta-cyclodextrin at 15 degrees C. Addition of 5 M urea to the running
      buffer containing beta-cyclodextrin at high concentrations resulted in the
      enantioseparation of prilocaine, mepivacaine, and ketamine. Enantioresolution was
      improved upon the addition of 10% methanol to the buffer containing urea and beta
      cyclodextrin. Generally, the complex formed between the S-enantiomers and
      modified beta-cyclodextrins was stronger than the corresponding R-forms. An
      exception was prilocaine where the R-form gave a more stable complex both with
      alpha- and beta-cyclodextrin.

PMID- 9629908
TI  - Dual chiral recognition system involving cyclodextrin derivatives in capillary
      electrophoresis II. Enhancement of enantioselectivity.
AB  - The enantiomer separation of hexobarbital was investigated by open tubular
      electrochromatography (OTEC) using the chiral stationary phase (CSP) CHIRASIL-DEX
      (a permethylated beta-cyclodextrin covalently linked to a dimethylpolysiloxane)
      and by cyclodextrin-electrokinetic chromatogaphy (CD-EKC) using anionic beta
      cyclodextrin-sulfo-n-propyl ether (SPE-beta-CD) and cationic beta-cyclodextrin-2
      hydroxy-3-trimethylammoniumpropyl ether chloride (HTAP-beta-CD) added to the
      running buffer. By employing two chiral selectors, the enantiomer separation of
      hexobarbital was then studied simultaneously by OTEC with CHIRASIL-DEX and by CD
      EKC with either SPE-beta-CD or HTAP-beta-CD in the dual chiral recognition mode.
      In conjunction with CHIRASIL-DEX, anionic SPE-beta-CD decreased the chiral
      separation factor alpha due to compensation of enantioselectivity whereas the
      cationic additive HTAP-beta-CD increased the chiral separation factor alpha due
      to enhancement of enantioselectivity. It is concluded that CHIRASIL-DEX imparts
      an opposite enantioselectivity to the enantiomers of hexobarbital as compared to
      the charged CDs SPE-beta-CD and HTAP-beta-CD. Unusual peak broadening phenomena
      are observed in the dual chiral recognition system comprised of CHIRASIL-DEX and
      HTAP-beta-CD. The possible consequences of accidental dual chiral recognition
      systems caused by wall stacking effects of the mobile phase additives onto the
      inner surface of the capillary column are discussed.

PMID- 9629909
TI  - Molecular size and net charge of pathogenesis-related enzymes from barley
      (Hordeum vulgare L., v. Karat) infected with Drechslera teres f. teres (Sacch.)
      Shoem.
AB  - Molecular size and net charge of isoforms of pathogenesis-related (PR) chitinase,
      beta-1,3-glucanase and peroxidase were studied in uninfected barley (Hordeum
      vulgare L., v. Karat) leaves and in barley leaves infected with the pathogenic
      fungus Drechslera teres f. teres (Sacch.) Shoem. Molecular characteristics were
      determined by time-dependent polyacrylamide gradient gel electrophoresis under
      native conditions and by applying an extended version of the computer program MOL
      MASS (Rothe, G. M., Weidmann, H., Electrophoresis 1991, 12, 703-709). Uninfected
      barley leaves contained predominantly one peroxidase isozyme but also three very
      weak peroxidases. Activities of all of these three peroxidases increased
      considerably after infection with Drechslera teres. The molecular masses of
      peroxidases 1 and 3 were estimated to be 38 +/- 5 and 42 +/- 7 kDa and their
      apparent valences at pH 8.4 were Z = 3.13 and 3.20, respectively. Amongst the
      chitinase isoforms, chitinase 1 and chitinase 2 appeared after infection, while
      chitinase 3 was also observed in uninfected leaves of barley. The molecular mass
      of chitinase 3 (31 +/- 6 kDa; f/fo = 1.20) was larger than that of chitinase 1
      (20 +/- 2 kDa; f/fo = 1.04) and chitinase 2 (23 +/- 3 kDa; f/fo = 1.06). The
      valence of constitutive chitinase 3 (Z = 1.44 +/- 0.81) at pH 8.4 was lower than
      that of adaptive chitinase 1 (Z = 3.27 +/- 1.02) and chitinase 2 (Z = 2.96 +/-
      1.38). Infection of barley leaves with Drechslera teres also induced the
      hydrolytic enzyme beta-1,3-glucanase 1; beta-1,3-glucanase 2 appeared in
      uninfected and in infected leaves. Constitutive beta-1,3-glucanase 2 was smaller
      (molecular mass 19 +/- kDa; f/fo = 1.05) than adaptive beta-1,3-glucanase 1
      (molecular mass 26 +/- 4 kDa; f/fo = 1.07). The valence of adaptive beta-1,3
      glucanase 1 (Z = 9.58 +/- 4.17) was approximately threefold that of beta-1,3
      glucanase 2 (Z = 2.80 +/- 0.93).

PMID- 9629910
TI  - Two replica blotting methods for fast immunological analysis of common proteins
      in two-dimensional electrophoresis.
AB  - The combination of two-dimensional electrophoresis (2-DE) and subsequent Western
      blot analysis with antibodies directed against common cellular proteins is a
      straightforward and reliable method to quickly generate fix points in a protein
      map. In order to assure high accuracy in the allocation of protein spots, two
      different replica blotting methods for semidry blotting devices were established.
      The first of the two was described by Johansson (Electrophoresis 1987, 8, 379
      383). By systematically changing the direction of the blotting current, proteins
      were simultaneously transferred from one gel onto two membranes placed at both
      sides of the gel. However, several modifications of this method were necessary in
      order to use a semidry blotting device. The second method described here combines
      the standard blotting procedure with the generation of a 'contact copy' from the
      gel. Both systems offer the possibility to subject one membrane to antibody
      mediated imaging, while the second membrane can be stained with highly sensitive
      total protein detection procedures. Protein identification is then carried out by
      comparing the signals on both matrices.

PMID- 9629911
TI  - Use of thiourea to increase the solubility of membrane proteins in two
      dimensional electrophoresis.
AB  - The separation of membrane proteins by high-resolution two-dimensional
      electrophoresis was carried out. At high loads, these proteins are prone to
      precipitation, resulting in poor resolution. It is shown here that the use of
      thiourea, previously described for focusing in immobilized pH gradients, can be
      extended to conventional isoelectric focusing. As thiourea inhibits acrylamide
      polymerization, a modified photopolymerization system must be used. These
      modifications result in higher solubility of proteins during IEF, thereby
      increasing the resolution and capacity of the two-dimensional gels.

PMID- 9629912
TI  - Two-dimensional map of basic proteins of Haemophilus influenzae.
AB  - Haemophilus influenzae is a bacterium of medical interest of which the entire
      genome has been sequenced. The proteome of the microorganism has been analyzed by
      two-dimensional gel electrophoresis, during which immobilized pH 3-10 gradient
      strips were used and approximately 300 proteins were identified. In order to
      detect additional, basic proteins, we analyzed the soluble protein fraction of H.
      influenzae and the proteins of fractions collected from affinity chromatography
      on heparin, by two-dimensional gel electrophoresis, using for the first
      dimensional separation immobilized pH gradient strips comprising the pH region of
      6-11. The protein spots were analyzed by matrix-assisted laser desorption
      ionization-mass spectrometry. One hundred and two proteins were identified, of
      which 58 were identified for the first time. A large percentage of the basic
      proteins represent nucleic acid binding and, in particular, ribosomal proteins.
      The locations of the identified basic proteins of H. influenzae are indicated in
      a two-dimensional map.

PMID- 9629913
TI  - Evidence of intra- and extracellular modifications of monoclonal IgG polypeptide
      chains generating charge heterogeneity.
AB  - The heavy and light chains of IgG monoclonal antibodies (mAbs) can be shown to be
      heterogeneous, with respect to isoelectric points, when analyzed by two
      dimensional electrophoresis (2-DE). The molecular basis for this charge
      heterogeneity has not been clearly defined but it has been suggested that it
      could be due, in part, to differences in glycosylation. To investigate this
      possibility we have compared the 2-DE pattern of glycosylated and aglycosylated
      forms of the mouse IgG1 mAb (1B7-11), produced in vitro in the presence and
      absence of tunicamycin. Charge heterogeneity was shown not to be a consequence of
      glycosylation status. Intracellular and secreted IgG mAbs were also analyzed to
      investigate the time course of change in charge properties of the heavy and light
      chains. The charge heterogeneity was found to be generated intracellularly, and
      alterations in charge properties could be induced during incubation under
      physiological conditions. Semilogarithmic plots of the density of the principal
      heavy and light chain spots against incubation time showed linear relationships,
      suggesting that the charge shifts result from a first-order reaction. The
      semilogarithmic plot for the light chain correlated well with the time after IgG
      synthesis. These results suggest that the charge heterogeneity of an IgG mAb is
      due to intra- and extracellular modifications of the polypeptide chains which
      reflect "aging" of antibody molecules.

PMID- 9629914
TI  - A two-dimensional electrophoretic study of serum amyloid A and C-reactive protein
      in infants and children.
AB  - Two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) was used to analyze
      C-reactive - (CRP) and serum amyloid A protein (SAA) in infants and children.
      Five SAA isotypes were identified. CRP showed vertical streaking, and its optical
      density values correlated with immunoturbidimetric measurements. As evaluated by
      densitometry, both proteins showed an age-dependent variation. In more than 50%
      of the neonates, SAA was present in equal or higher amounts than CRP, and only
      SAA1alpha could be detected. In children, CRP was expressed in higher amounts
      than SAA, and both SAA1alpha and SAA2alpha were present. N-terminally modified
      forms of both isotypes were present regardless of age, including in premature
      infants. These results suggest that the overall synthesis of the gene products
      SAA1alpha and SAA2alpha is developmentally regulated, but at the same time that
      their N-terminal processing occurs independently of developmental factors. The
      presented data suggest that SAA has an important function in neonates, and that
      the role of SAA as an infection marker in this population should be investigated
      further.

PMID- 9629915
TI  - Two-dimensional zymography for analysis of proteolytic enzymes in human pure
      pancreatic juice.
AB  - Proteolytic enzymes in human pure pancreatic juice (PPJ), which was collected by
      cannulating the main pancreatic duct using endoscopy, were investigated by two
      dimensional zymography (2-DZ). 2-DZ was carried out by combining isoelectric
      focusing (IEF) in the first dimension with sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis (SDS-PAGE) in the second dimension, using gels containing
      casein or gelatin as a substrate for the proteolytic enzymes. After
      electrophoresis, the gels were incubated in Triton X-100 followed by incubation
      at 37 degrees C in Tris buffer (pH 8.5) containing CaCl2. By staining the gels
      with Coomassie Brilliant Blue (CBB R-250), proteolytic enzymes were detected as
      clear spots and zones against a blue background. Proteinase inhibitors, such as a
      cysteine proteinase inhibitor (E-64), a metalloproteinase inhibitor (EDTA), and a
      serine proteinase inhibitor (Pefabloc SC), were added to PPJ in order to
      determine the types of proteinases. In patients with pancreatic cancer, spots of
      molecular weight (Mr) 70,000 and isoelectric points (pI) 5.3-5.5 were clearly
      detected on the gels containing casein and gelatin, while these spots were not
      detected in the PPJ from healthy subjects. The proteolytic activities of these
      spots were strongly inhibited by EDTA and Pefabloc SC but not E-64. These results
      suggest that the spots of Mr 70,000 and pI 5.3-5.5 in PPJ of pancreatic cancer
      might be matrix metalloproteinase 2, which is a candidate for tumor-associated
      proteinase. 2-DZ proved to be a tool for analysis of proteolytic enzymes in PPJ
      and for the clinical diagnosis of pancreatic cancer.

PMID- 9629916
TI  - Divergent and common groups of proteins in glands of venomous snakes.
AB  - Protein contents of venom-producing glands from the sea-snake Laticauda colubrina
      (LC) and terrestrial Vipera Russelli (VR) were studied using high-resolution two
      dimensional gels: isoelectric focusing followed by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (IEF/SDS-PAGE) and nonequilibrium pH gradient
      electrophoresis (NEPHGE) followed by SDS-PAGE. Tentative identities of numerous
      proteins were established using their amino acid compositions and in certain
      cases the identities were verified by microsequencing of their N-terminals and
      internal fragments. As expected, we found several proteins known to be present in
      the venom of the respective snakes. These include numerous isoforms of
      phospholipase A2 (PLA2) in both snake glands, various neurotoxins in LC glands
      and factor IX/factor X-binding protein, hemorrhagic factor and coagulation factor
      X activating enzyme in Russell's viper glands (VR). Not unexpectedly, we also
      found a number of cell housekeeping proteins, cytoskeletal proteins, proteins
      that are necessary for folding, such as heat-shock proteins, protein disulfide
      isomerase and peptidyl-prolyl cis/trans isomerases. Unexpectedly, however, the
      glands of Laticauda colubrina and Russell's viper include a large quantity of
      antihemorrhagic factor and inhibitor of PLA2, respectively, that have been
      previously described in snake plasma. The possible reason associated with the
      presence of these components in venom glands is discussed.

PMID- 9629917
TI  - Two-dimensional polyacrylamide gel electrophoresis map of bull seminal plasma
      proteins.
AB  - A two-dimensional polyacrylamide gel electrophoresis map of bull seminal plasma
      proteins has been established. About 250 spots were detected after silver
      staining and polypeptides from 24 spots have been N-terminally sequenced. Major
      proteins already described in bull seminal plasma, like PDC-109 and aSFP, have
      been located on the map; proteins not yet reported in male reproductive tracts
      have been evidenced; for some polypeptides showing a previously unknown N
      terminal sequence, structural similarities with proteins described in other
      organisms have been found. A reference map of seminal plasma proteins could be
      useful in relating protein pattern changes to physiopathological events
      influencing the reproductive sphere.

PMID- 9629918
TI  - Two-dimensional gel electrophoresis separation and N-terminal sequence analysis
      of proteins from Clostridium pasteurianum W5.
AB  - Proteins from Clostridium pasteurianum were separated by two-dimensional gel
      electrophoresis. Amino-terminal sequence determination and sequence analysis
      allowed the identification of 20 proteins, while 11 protein sequences remained
      unidentified and one protein appeared to have a blocked amino terminus.

PMID- 9629919
TI  - Bright sparks in Australian 2-DE: report on the Fourth Annual Conference of the
      Australian Electrophoresis Society.

PMID- 9629920
TI  - Two-dimensional electrophoretic analysis of mixed lineage kinase 2 N-terminal
      domain binding proteins.
AB  - The mixed lineage kinase 2 (MLK2) protein contains several structurally distinct
      domains including an src homology (SH) 3 domain, a kinase catalytic domain, two
      leucine zippers, a basic motif and a cdc42/rac interactive binding motif. These
      domains have been recognized mainly for their involvement in protein-protein
      interactions in signal transduction networks. The SH3 domain in particular has
      been implicated in control of signaling events. To identify proteins that
      interact with MLK2, the N-terminal 100 amino acids, including the SH3 domain,
      were expressed as a glutathione S-transferase (GST) fusion protein. This fusion
      protein (MLK2N) was used as an affinity ligand to isolate binding proteins from
      lysates of 35S-radiolabeled MDA-MB231 breast carcinoma cells. When the
      radiolabeled binding proteins were subjected to 2-DE, proteins of Mr 55,000,
      31,500 and 34,000 bound consistently to the MLK2N domain fusion protein, but not
      to the GST control. Two of the binding proteins were isolated from whole cell
      lysates by preparative 2-DE and subjected to in-gel digestion and capillary or
      microbore reverse-phase high performance liquid chromatography (RP-HPLC).
      Resultant peptides were analyzed by peptide mass fingerprinting, N-terminal Edman
      degradation or tandem mass spectrometry. The 55,000 protein was identified as the
      cytoskeletal protein, beta-tubulin, and this was verified by immunoblotting of
      proteins in the MLK2N binding fraction with anti-tubulin antibodies. The 31,500
      protein has been identified as prohibitin, a protein that has been implicated in
      both signal transduction and cell cycle arrest.

PMID- 9629921
TI  - Two-dimensional gel database of human breast carcinoma cell expressed proteins:
      an update.
AB  - Previously, we reported a two-dimensional gel map and database with molecular
      weight/isoelectric point (Mr/pI) loci for 22 proteins expressed in the breast
      carcinoma cell line, MDA-MB231 (Rasmussen et al., Electrophoresis 1997, 18, 588
      598). Here we update this database with Mr/pI loci for a further nine cytoplasmic
      proteins and three Triton X-114 solubilised membrane proteins from MDA-MB231
      cells. In addition, a novel protein, previously represented only in expressed
      sequence tag (EST) databases, has been identified as a Triton X-114 soluble
      protein and assigned an Mr/pI locus. During the course of isolating proteins from
      the Triton X-114 fraction, we compared recoveries of proteins in sodium dodecyl
      sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) gels after isoelectric
      focusing (IEF) using either immobilised pH gradients or carrier ampholytes. In
      these experiments, a significantly higher proportion of membrane proteins were
      visible in SDS-polyacrylamide gels after the use of carrier ampholytes for the
      first dimension. We also report our mass spectrometric-based procedure for
      identifying two-dimensional electrophoresis (2-DE) gel-resolved proteins,
      combining in-gel enzymatic digestion, 0.2 mm internal diameter (ID) capillary
      column reversed-phase high-performance liquid chromatography (RP-HPLC) peptide
      mapping and electrospray ionisation--ion trap--mass spectrometry.

PMID- 9629922
TI  - Actin-binding proteins in mouse C2 myoblasts and myotubes: a combination of
      affinity chromatography and two-dimensional gel electrophoresis.
AB  - This paper analyzes proteins expressed in a mouse muscle precursor cell line (C2
      myoblasts) and compares them with those observed in differentiated myotubes from
      the same cell line. We observed hundreds of proteins in myoblasts using IPG two
      dimensional gel electrophoresis but this number is greatly reduced using Mini
      Leak (divinylsulfone-activated agarose) affinity chromatography. Two kinds of
      affinity columns were prepared. One contained a chemically modified monomeric
      actin bound to the affinity matrix. The second matrix contained a high-affinity
      actin-binding protein (DNase I) which was bound to the actin Mini-Leak column to
      block specific sites on actin. Actin-binding proteins in homogenates of myoblasts
      or myotubes were passed through the affinity columns and eluted under high salt
      conditions. The Mini-Leak affinity medium itself appeared to have little ability
      to bind proteins. Our two-dimensional (2-D) gels identified a small number of
      proteins and we are currently focusing our attention on a particular protein spot
      which could correspond to cofilin. Comparison of myoblast and myotube proteins
      using affinity chromatography shows no qualitative, clearly identifiable
      differences but the analysis is still in progress. These findings are discussed
      in relation to reports in which the myoblast-myotube transformation was
      associated with the up-regulation or de novo synthesis of more than ten proteins.

PMID- 9629923
TI  - Development of a two-dimensional gel electrophoresis database of human lysosomal
      proteins.
AB  - Two-dimensional gel electrophoresis databases have been generated for a range of
      tissue cell and fluid types, from a number of species. A major difficulty in the
      development of such databases is the large number of proteins present in even a
      single cell type (> 10,000) and the low levels of many of these proteins. One
      approach to overcome these difficulties is to fractionate the cell into its
      organelles and generate individual databases for each subcellular component. This
      has the added advantage of assigning a cellular location to each protein
      identified. Here we report the development of a two-dimensional gel
      electrophoresis database of lysosomal proteins.

PMID- 9629924
TI  - Extraction of membrane proteins by differential solubilization for separation
      using two-dimensional gel electrophoresis.
AB  - We describe the extraction and enrichment of membrane proteins for separation by
      two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) after differential
      solubilization of an Escherichia coli cell lysate. In a simple three-step
      sequential solubilization protocol applicable for whole cell lysates, membrane
      proteins are partitioned from other cellular proteins by their insolubility in
      solutions conventionally used for isoelectric focusing (IEF). As the first step,
      Tris-base was used to solubilize many cytosolic proteins. The resultant pellet
      was then subjected to conventional solubilizing solutions (urea, 3-[(3
      cholamidopropyl)dimethylammonio]-1-propanesulfonate, dithiothreitol, Tris,
      carrier ampholytes). Following the completion of this step, 89% of the initial E.
      coli sample mass was solubilized. Finally, the membrane protein rich pellet was
      partially solubilized using a combination of urea, thiourea, tributyl phosphine
      and multiple zwitterionic surfactants. Using N-terminal sequence tagging and
      peptide mass fingerprinting we have identified 11 membrane proteins from this
      pellet. Two of these outer membrane proteins (Omp), OmpW and OmpX, have
      previously been known only as an open reading frame in E. coli, while OmpC, OmpT
      and OmpTOLC have not previously been identified on a 2-D gel. The
      prefractionation of an entire cell lysate into multiple fractions, based on
      solubility, results in simplified protein patterns following 2-D PAGE using broad
      range pH 3.5-10 immobilized pH gradients (IPGs). Additional advantages of sample
      prefractionation are that protein identification and gel matching, for database
      construction, is a more manageable task, the procedure requires no specialized
      apparatus, and the sequential extraction is conducted in a single centrifuge
      tube, minimizing protein loss.

PMID- 9629925
TI  - Improved protein solubility in two-dimensional electrophoresis using tributyl
      phosphine as reducing agent.
AB  - In this study, dithiothreitol was replaced by tributyl phosphine as the reducing
      agent in both the sample solution for the first-dimensional isoelectric focusing
      and during the immobilised pH gradient (IPG) equilibration procedure. Tributyl
      phosphine improves protein solubility during isoelectric focusing, which results
      in shorter run times and increased resolution. Tributyl phosphine is nonionic and
      thus does not migrate in the IPG, therefore maintaining reducing conditions
      during the course of the first-dimensional separation. The increased solubility
      provided by the maintenance of reducing conditions gives improved focusing and
      decreased horizontal streaking on the subsequent second-dimension gel. The use of
      tributyl phosphine in the equilibration step allows the procedure to be
      simplified, incorporating reduction and alkylation in a single step. This is
      possible because, in direct contrast to dithiothreitol (DTT), tributyl phosphine
      does not contain a free thiol and therefore does not react with thiol-specific
      alkylating reagents.

PMID- 9629926
TI  - Development of mini-gel technology in two-dimensional electrophoresis for mass
      screening of samples: application to tears.
AB  - Despite the extensive literature available on tear proteins and lipids, very
      little has been reported on the tear fluid as a whole and it's changes in contact
      lens wear or ocular diseased patients. Initially a human reflex tear two
      dimensional map was created by Molloy et al. (Electrophoresis 1997, 18, 2811
      2815), using this information a process for mass-screening was established. The
      large format two-dimensional technique was evaluated, using a basal tear
      reference map, and modified to describe a fast, efficient and cost effective
      method of protein separation. The use of one pH 3-10 18 cm nonlinear immobilised
      pH gradient (IPG) strip and two mini-gels for the second-dimensional sodium
      dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) results in an
      effective separation of tear proteins which will be applied in diagnostic studies
      of tear samples.

PMID- 9629927
TI  - Alterations in the expression of P2X1 receptors in failing and nondiseased human
      atria.
AB  - This is the first report of the analysis of the ATP-specific P2X1 receptor
      subunit in human hearts. We have examined homogenate samples of human left atria
      for the presence of P2X1 receptors using Western blots. Anti-P2X1
      immunoreactivity was detected in populations of nondiseased atria as well as in
      atria from explanted hearts from patients with terminally failing heart
      conditions such as dilated cardiomyopathy. At least three groups of P2X1
      immunoreactive proteins were detected in the Western blots with approximate
      molecular mass values of 50, 70, and 160 kDa. We report changes in expression of
      their 50 and 70 kDa components. These changes may be related to the type of
      deficit in these hearts since the changes have been observed in hearts with
      decreased ejection fractions characteristic of dilated cardiomyopathy.

PMID- 9629928
TI  - Direct cloning of polymerase chain reaction products into the pinpoint Xa1-T
      vector protein expression system.
AB  - Expression of recombinant proteins is an important method for the
      characterisation of the structure and function of proteins. However, many
      expression methods can be difficult, time-consuming and lead to low protein
      yields. The Promega Pinpoint Xal-T vector system is a unique, one-step cloning
      method that allows the direct insertion of polymerase chain reaction (PCR)
      fragments into the expression vector. We describe our experience of the use of
      this system to clone and express three proteins (8-12 kDa) directly from their
      PCR products. The proteins are expressed as fusion proteins with a 13 kDa
      biotinylated tag that can be used for detection of the expressed protein and
      affinity purification. In our case, the yield was greater than 20 mg per litre of
      culture. Expressed proteins were purified by Q-Sepharose anion-exchange
      chromatography and reverse-phase high-performance liquid chromatography (HPLC)
      instead of the conventional method of avidin-biotin affinity chromatography. The
      Pinpoint vector proved to be a relatively simple and fast protein expression
      technique suitable for wide application for expressing recombinant proteins.

PMID- 9629929
TI  - Characterization of rat brain stathmin isoforms by two-dimensional gel
      electrophoresis-matrix assisted laser desorption/ionization and electrospray
      ionization-ion trap mass spectrometry.
AB  - Stathmin is a regulatory phosphoprotein that is a target for both cell cycle and
      cell surface receptor-regulated phosphorylation events. There are at least 14
      isoforms of stathmin that migrate on two-dimensional electrophoresis (2-DE): two
      unphosphorylated, and 12 increasingly phosphorylated proteins. Following
      extracellular stimuli, stathmin is phosphorylated on four serines (Ser16, Ser25,
      Ser38, and Ser63) by several kinases, such as mitogen-activated protein (MAP),
      cdc2 kinase, protein kinase A, and Ca2+/calmodulin-dependent kinase-Gr. While all
      forms of stathmin are derived from the same protein encoded by a single mRNA, the
      precise nature of the post-translational modifications has not been clear. In
      this study we have characterized three rat brain stathmin isoforms, #1, #3 and
      #4, which electrophorese on 2-DE with apparent molecular weight (Mr)/isoelectric
      point (pI) values of 15,500/6.2, 15,000/6.1, and 15,000/6.0, respectively. The
      phosphorylation status of these isoforms was determined using a combination of
      peptide mapping, matrix-assisted laser desorption/ionization mass spectrometry
      and electrospray-ionization ion trap mass spectrometry. Stathmin isoform #1 was
      not phosphorylated, stathmin isoform #3 was phosphorylated on Ser38 only, and
      stathmin isoform #4 was phosphorylated on Ser38; however, the phosphorylation
      status of Ser63 could not be determined. In addition, three proteins which
      electrophorese near stathmin were identified in order to more accurately define
      the Mr/pI locus of this region of the 2-DE gel map. These include: phosphatidyl
      ethanolamine binding protein (Mr approximately 18,000/pI 6.0), synuclein forms 2
      and 3 (Mr approximately 14,000/pI 5.4), and synuclein form 2 (Mr approximately
      15,000/pI 5.0).

PMID- 9629930
TI  - An algorithm for selection of instrumentation levels in scoliosis.
AB  - Appropriate levels for instrumentation and fusion in scoliosis have been a matter
      of debate among surgeons since the introduction of operative management of this
      deformity. We set out to examine the hypothesis that the amount of correction
      achieved in all planes during surgical instrumentation of a curve should be less
      than, or comparable to, the degree of correction attainable at any non
      instrumented adjacent curve. An algorithm was designed to facilitate preoperative
      planning and intraoperative performance of spinal fusion procedures in the
      management of scoliosis. To test the validity of the hypothesis and the proposed
      algorithm, measurements were taken from the preoperative radiographs of 200
      patients. The dimensions of the curves were obtained from an initial set of four
      X-ray films: (1) standing anteroposterior film of the whole spine, (2) standing
      lateral film of the whole spine, (3) two properly performed side-bending films
      including each curve of the spine. With this data, a plan was designed using the
      algorithm. The results of this plan were compared with the actual results of the
      surgery, which were revealed only at this stage. All patients in whom actual
      instrumentation levels fell within those predicted by the proposed algorithm had
      no imbalance at follow-up. All patients whose actual instrumentation levels were
      short of those recommended by the algorithm showed obvious imbalance on final
      postoperative standing radiograph.

PMID- 9629931
TI  - Gait asymmetries in patients with idiopathic scoliosis using vertical forces
      measurement only.
AB  - This study aimed at identifying measurable asymmetries during gait and relating
      them to the spinal deformity in subjects with idiopathic scoliosis. We
      investigated 21 patients aged between 10 and 26 years for gait asymmetries using
      force plates. All subjects completed five walking cycles over two force plates
      measuring vertical ground reaction forces. Among the parameters measured were
      contact time and magnitude of the two peaks of the vertical forces as well as the
      rate of application of those forces. Published gait data on normal subjects were
      used as a control group. In 20 subjects an asymmetry of at least one gait
      parameter was noted. Multiple regression analysis showed, however, that there was
      no relation between the noted gait asymmetry and the curve direction, curve
      magnitude or vertebral rotation. This suggests that although functional
      asymmetries of the central nervous system have been described in patients with
      idiopathic scoliosis, they do not appear to have a reproducible effect on gait.

PMID- 9629932
TI  - Pelvic incidence: a fundamental pelvic parameter for three-dimensional regulation
      of spinal sagittal curves.
AB  - This paper proposes an anatomical parameter, the pelvic incidence, as the key
      factor for managing the spinal balance. Pelvic and spinal sagittal parameters
      were investigated for normal and scoliotic adult subjects. The relation between
      pelvic orientation, and spinal sagittal balance was examined by statistical
      analysis. A close relationship was observed, for both normal and scoliotic
      subjects, between the anatomical parameter of pelvic incidence and the sacral
      slope, which strongly determines lumbar lordosis. Taking into account the Cobb
      angle and the apical vertebral rotation confers a three-dimensional aspect to
      this chain of relations between pelvis and spine. A predictive equation of
      lordosis is postulated. The pelvic incidence appears to be the main axis of the
      sagittal balance of the spine. It controls spinal curves in accordance with the
      adaptability of the other parameters.

PMID- 9629933
TI  - Polysegmental lumbar posterior wedge osteotomies for correction of kyphosis in
      ankylosing spondylitis.
AB  - Between 1984 and 1993 we treated 21 consecutive patients who had progressive
      thoracic kyphosis due to ankylosing spondylitis by polysegmental posterior lumbar
      wedge osteotomies. In 19 patients we used the Universal Spinal Instrumentation
      System and in the last 2 patients the H-frame. The average correction in 20 of 21
      patients at follow-up was 25.6 degrees (range 0 degrees-52 degrees), with a mean
      segmental correction of 9.5 degrees and a mean loss of correction after operation
      of 10.7 degrees (range 0 degrees-36 degrees). There were no fatal complications,
      but in one patient no correction could be obtained during surgery and another
      patient was reoperated due to lack of correction. Breaking out of screws through
      the pedicle during compressive correction was seen in seven patients. Implant
      failure, such as breakage of the threaded rods and/or loosening of the junction
      between the pedicle screw and the rod, occurred in 9 out of 21 patients. Two
      patients required reoperation at long-term follow-up. Five out of seven deep
      wound infections required removal of the implant. Polysegmental lumbar wedge
      osteotomies for correction of progressive thoracic kyphosis in ankylosing
      spondylitis is only recommended in patients at a mild stage of the disease with
      mobile discs and in combination with strong instrumentation.

PMID- 9629934
TI  - A prospective, randomized 5-year follow-up study of functional restoration in
      chronic low back pain patients.
AB  - A functional restoration (FR) program, dealing with a combination of intensive
      physical and ergonomic training, psychological pain management, and patient
      education, was tested in two randomized, parallel group studies. In one of these
      patients following the FR program were compared with a non-treated control group
      (project A), and in the other with patients on two less intensive treatment
      programs (project B). A total of 238 chronic low back pain patients participated
      in the two studies, 106 entering project A and 132 project B. Patients from the
      two projects were comparable except that the patients in project A were recruited
      from all over the country, whereas patients in project B all were living in and
      around Copenhagen. Thirteen patients never started any treatment, and 20 patients
      (9%) dropped out during the treatment period. Of the 207 who completed treatment,
      89% returned a mailed questionnaire 5 years later. This was the case for 55% of
      the drop-outs. The questions referred to work situation, pain level, activities
      of daily living, days of sick leave, contact with health care professionals,
      physical activity, use of medication, and a subjective overall assessment. The
      results show that in project A the treated group reported significantly fewer
      contacts with the health care system and significantly fewer days of sick leave
      over the 5-year follow-up period compared to the control group. In all other
      parameters, including work ability, there was no statistically significant
      difference between the two groups. In project B, patients treated in the FR
      program did significantly better in most measured parameters, except in leg pain,
      use of pain medication and sport activity, where no significant differences were
      found between groups. The overall result shows a positive long-term effect of the
      FR program, but it also shows the necessity of testing a given treatment in
      different projects and designs, among other things due to statistical variations.

PMID- 9629935
TI  - Significance of patient-controlled analgesia in combination with continuous
      epidural block for patients who underwent posterior lumbar surgery.
AB  - The purpose of the study was to evaluate the efficiency of patient-controlled
      analgesia (PCA) combined with continuous epidural block in patients who underwent
      lumbar spine surgery. In group 1 (postoperative PCA group), 23 patients were
      administered postoperative continuous epidural block in combination with
      analgesics, which was self-regulated by the patient using a device. In contrast,
      the 22 patients in group 2 (control group) received suppositories or
      intramuscular injections of analgesics on request. The following factors were
      compared between the two groups: pain relief according to the visual analog scale
      for pain assessment, the frequency of administration of analgesics, and side
      effects of the postoperative analgesia. The patients in group 1 had more
      satisfactory relief of pain according to the visual analog scale for pain
      assessment and needed suppositories and intramuscular injection of analgesics
      less frequently on the 1st, 2nd, and 3rd postoperative day. The time spent by
      nurses on pain management in group 1 was less than that in group 2. No patient
      had any serious complications in either group. In conclusion, the present patient
      controlled method combined with postoperative continuous epidural block could
      decrease the intensity of postoperative pain and the amount of time spent by
      nurses on the administration of postoperative analgesics after lumbar spine
      surgery.

PMID- 9629936
TI  - Simultaneous combined anterior and posterior lumbar fusion with femoral cortical
      allograft.
AB  - The radiographic fusion rates, graft behaviour and clinical outcome of 41 patient
      with simultaneous combined anterior lumbar interbody fusion and posterior
      arthrodesis with translaminar screws were reviewed independently. In all patients
      a femoral cortical allograft (FCA) ring filled with autologous iliac crest
      cancellous bone was used anteriorly to replace the disc and achieve interbody
      fusion. The follow-up averaged 30.6 months, with a minimum follow-up of 24
      months. All patients had disabling low-back pain with different degrees of
      radiating leg pain and either discogenic pain (n = 24) or a postdiscectomy
      syndrome (n = 15) respectively postfusion syndrome (n = 2). The overall fusion
      rate was 95.2% (59 of 62 segments). Time to radiographic fusion averaged 8.7
      months (range 2-34 months), and in 66.1% radiographic fusion occurred without
      significant subsidence. In 18.6% fusion with subsidence resulted from resorption
      of the FCA and in 15.3% the FCA had protruded into the vertebral body. The
      posterior intervertebral disc height (PIVDH) increased postoperatively by 2 mm on
      average. However, loss of PIVDH was the rule, and occurred within the first 12
      postoperative months, resulting in a negligible final gain in height of 0.3 mm on
      average. The segmental lordosis was increased by 3 degrees; however, loss of
      lordosis during the first 6 postoperative months led to a final gain in lordosis
      of 1.3 degrees on average. Graft incorporation occurred in 16 of 62 segments
      (25.8%) and was observed at an average of 21.9 months postoperatively.
      Subjectively, 82.4% of the patients were satisfied or highly satisfied with the
      clinical result of the fusion operation. In conclusion, the described technique
      has proven to be highly effective in achieving a high fusion rate with a good
      patient outcome.

PMID- 9629937
TI  - Compressive strength of interbody cages in the lumbar spine: the effect of cage
      shape, posterior instrumentation and bone density.
AB  - One goal of interbody fusion is to increase the height of the degenerated disc
      space. Interbody cages in particular have been promoted with the claim that they
      can maintain the disc space better than other methods. There are many factors
      that can affect the disc height maintenance, including graft or cage design, the
      quality of the surrounding bone and the presence of supplementary posterior
      fixation. The present study is an in vitro biomechanical investigation of the
      compressive behaviour of three different interbody cage designs in a human
      cadaveric model. The effect of bone density and posterior instrumentation were
      assessed. Thirty-six lumbar functional spinal units were instrumented with one of
      three interbody cages: (1) a porous titanium implant with endplate fit (Stratec),
      (2) a porous, rectangular carbon-fibre implant (Brantigan) and (3) a porous,
      cylindrical threaded implant (Ray). Posterior instrumentation (USS) was applied
      to half of the specimens. All specimens were subjected to axial compression
      displacement until failure. Correlations between both the failure load and the
      load at 3 mm displacement with the bone density measurements were observed.
      Neither the cage design nor the presence of posterior instrumentation had a
      significant effect on the failure load. The loads at 3 mm were slightly less for
      the Stratec cage, implying lower axial stiffness, but were not different with
      posterior instrumentation. The large range of observed failure loads overlaps the
      potential in vivo compressive loads, implying that failure of the bone-implant
      interface may occur clinically. Preoperative measurements of bone density may be
      an effective tool to predict settling around interbody cages.

PMID- 9629938
TI  - Intervertebral disc distraction with a laparoscopic anterior spinal fusion
      system.
AB  - The BAK spinal fusion system has been applied to laparoscopic anterior lumbar
      interbody fusion. The system, consisting of a pair of cylindrical implants with
      threads, placed symmetrically about the sagittal plane, functions by tensioning
      the annulus fibrosis. Cylindrical plugs of increasing size are inserted prior to
      the implant placement. As the procedure may affect spinal posture and disc
      height, we measured changes due to incremental plug insertion using human
      cadaveric spine specimens (L5-S1, n = 4). Multi-directional flexibility of the
      construct was also measured as a function of plug size. The disc height change
      was found to increase initially and then to level off at 13-mm diameter plugs. In
      the sagittal plane, the intervertebral posture first shifted towards kyphotic
      then came back to the initial lordotic posture with plugs of bigger size.
      However, changes in disc height and spine posture were not statistically
      significant. Comparing the neutral zone (NZ) flexibility after inserting the
      plugs to the intact values, neither the flexion/extension nor the axial rotation
      NZ showed any significant change. In lateral bending, the NZ decreased after the
      insertion of 13-mm plugs (p < 0.05). Insertion of plugs of increasing size from 9
      mm to 12 mm decreased the range of motion (ROM) in all directions (p < 0.05).
      Insertion of 13-mm and 14-mm plugs decreased the flexion/extension and lateral
      bending ROM, but not the axial rotation ROM, probably indicating some injury to
      the annulus fibers.

PMID- 9629939
TI  - Testing criteria for spinal implants: recommendations for the standardization of
      in vitro stability testing of spinal implants.
AB  - New implants and new surgical approaches should be tested in vitro for primary
      stability in standardized laboratory tests in order to decide the most
      appropriate approach before being accepted for clinical use. Due to the complex
      and still unknown loading of the spine in vivo a variety of different test
      loading conditions have been used, making comparison of the results from
      different groups almost impossible. This recommendation was developed in a series
      of workshops with research scientists, orthopedic and trauma surgeons, and
      research and development executives from spinal implant companies. The purpose
      was to agree on in vitro testing conditions that would allow results from various
      research groups to be compared. This paper describes the recommended loading
      methods, specimen conditions, and analysis parameters resulting from these
      workshops.

PMID- 9629940
TI  - Thoracic scoliosis and restricted neck motion: a new syndrome? A report of six
      cases.
AB  - The cases of six adolescent males with a mild thoracic scoliosis of unknown
      etiology and a marked limitation of neck flexion are reported. All six complained
      of mild thoracic spine pain and were 13-17 years old at the onset of their
      symptoms. In addition to the thoracic scoliosis, all were found to have a marked
      limitation of neck flexion. They were unable to touch their chest wall with their
      chin. None had a positive family history of scoliosis. Radiological examination
      revealed a thoracic scoliosis of 10 degrees-40 degrees, no abnormalities were
      detected on cervical spine plain radiographs. Extensive investigations, including
      MRI of the entire spine, failed to disclose the cause of the spinal deformity or
      the mechanism causing the limitation of neck motion. Apart from the limited
      cervical flexion and mild pain, this condition was found to be benign and the
      spine deformity to be mild or moderate in nature and with limited progression.
      Review of the literature failed to identify similar cases.

PMID- 9629941
TI  - Vertebral hydatid cyst infection (Echinococcus granulosus): a case report.
AB  - Spinal echinococcosis is a rare but serious condition. Within bone tissue hydatid
      cysts enlarge by daughter cyst formation. The value of drug treatment in bone
      echinococcosis is questionable. The aim of surgery is therefore removal of all
      the cysts. The best way to achieve this is at the first operation early in the
      progress of the disease. An anterior or circumferential approach is generally
      required to give the necessary accessibility. Owing to diffuse spread of the
      infection within the bone and the canal, recurrence is common. If neurological
      deterioration occurs, reintervention is necessary.

PMID- 9629942
TI  - Intradural spinal hydatid cysts.
AB  - Spinal hydatid cysts are very rare and comprise only 1% of all bony involvement.
      Intradural hydatid cysts are extremely rare compared to other types of spinal
      hydatid cysts. We report the case of a 19-year-old man with lumbar intradural
      hydatid cysts. He complained of paraparesis and urinary hesitancy. Myelography
      revealed a block of the contrast medium at the L4 level and multiple round
      radiolucent lesions rostrally. At surgery, multiple hydatid intradural cysts were
      extirpated. The patient's neurologic deficits improved postoperatively, but
      recurred 6 weeks later. Reoperation led to partial improvement of deficits.
      Primary intradural hydatid cysts are extremely rare. It is difficult to explain
      an isolated intradural location of multiple cysts. In our patient, the cysts were
      multiple and the patient's cerebral CT scan was normal; he had undergone no
      previous lumbar puncture. So we can hypothesize that intradural spinal cysts may
      be primarily multiple.

PMID- 9629943
TI  - Vertebral osteomyelitis as a complication of Crohn's disease.
AB  - Vertebral osteomyelitis arising from an enteric fistula in patients with
      inflammatory bowel disease is rare. We report on a patient with Crohn's disease
      who developed an enteric fistula, resulting in a presacral abscess and vertebral
      osteomyelitis involving the L4 and L5 vertebral bodies and related disc spaces.
      This was managed by a defunctioning colostomy with drainage of the pre-sacral
      abscess. The vertebral lesion was successfully managed non-operatively.

PMID- 9629944
TI  - Intramedullary spinal tuberculoma presenting as a conus tumor: a case report and
      review of the literature.
AB  - Intramedullary spinal tuberculoma is a rare form of central nervous system
      tuberculosis. Although tuberculosis is unusual in the west, it is still prevalent
      in Asia and Africa. We report a case in which the diagnosis was made
      histologically without evidence of symptoms of systemic tuberculosis. The lesion,
      located in the conus medullaris, mimicked a conus tumor. The patient was a 20
      year-old man who presented with a history of progressive leg weakness, urinary
      urgency, and impotence. There was no history of, or recent contact with,
      tuberculosis. A diagnosis of an intramedullary tumor in the conus medullaris was
      made by MRI. The patient underwent a T11-L1 laminectomy and total resection of
      the lesion with microsurgical technique. Histologic examination revealed a
      granulomatous lesion containing Langhans' giant cells, inflammatory cells, and
      caseating necrosis. Antituberculous medication was instituted as soon as the
      diagnosis was made. Neurologic symptoms and signs slowly improved
      postoperatively. A combination of microsurgical resection and antituberculous
      chemotherapy should be the choice of treatment for intramedullary tuberculomas.

PMID- 9629945
TI  - Ossification of the posterior longitudinal ligament in Down's syndrome.
AB  - Cervical myelopathy in patients with Down's syndrome is not uncommonly the result
      of atlanto-axial instability, a condition that is caused by ligamentous laxity
      and which may be associated with congenital osseous anomalies at the occipito
      atlanto-axial axis. Ossification of the posterior longitudinal ligament (OPLL) is
      well described, particularly in the Japanese population, and may be associated
      with diffuse idiopathic skeletal hyperostosis. This is the first case, to our
      knowledge, of OPLL occurring in a person with Down's syndrome presenting with
      myelopathy.

PMID- 9629946
TI  - Risk factors and predictive signs of postpartum depression.
AB  - BACKGROUND: Depressed new mothers usually do not seek and therefore do not
      receive any psychiatric help. METHODS: In order to assess predictive signs of
      postpartum depression (PPD), an unselected sample of 570 women were seen by
      midwives during their pregnancy, using a questionnaire elaborated by ourselves
      and Derogatis' Hopkins Symptom Checklist. Three months after delivery each new
      mother was examined again by the same midwife using Cox' Edinburgh Postnatal
      Depression Scale. The medical files were also examined. RESULTS: Of the new
      mothers, 58 (10.2%) suffered from PPD. Most significant factors were socio
      professional difficulties, multiparity, deleterious life events, depressive mood
      prior to delivery, early mother-child separation and negative birth experience.
      The coping abilities of the depressed mother were decreased and her vulnerability
      to new stress factors increased. CONCLUSION: It is possible to detect women at
      risk for PPD already during pregnancy. We therefore elaborated a very simple,
      short predictive scale which is in the process of validation. LIMITATION:
      Protective factors still have to be studied. CLINICAL RELEVANCE: Knowledge of
      these factors should help all caregivers to recognize, during pregnancy, women at
      risk for PPD, in order to initiate preventive and/or therapeutic measures.

PMID- 9629947
TI  - Does sleep EEG data distinguish between UP, BPI or BPII major depressions? An age
      and gender controlled study.
AB  - Clinical characteristics and sleep EEG data of 14 unipolar (UPR), 14 bipolar I
      (BPI) and 14 bipolar II (BPII) patients, matched for age and gender, were
      investigated during a major depressive episode. We observed a remarkable
      similarity in the clinical characteristics of the three samples and, concerning
      sleep EEG data, a trend to a higher percentage of awakening among BPI patients.
      Pairwise comparisons of the three subgroups showed that only the Newcastle rating
      scale score reached significant difference between BPI and UPR groups. We
      observed trends regarding the difference of awakening both between BPI and BPII
      groups and between BPI and UPR groups, difference of percentage of REM sleep
      between BPI and BPII groups and difference of Sleep Period Time between BPII and
      UPR groups. We also observed that the distribution of REM latencies in the BPI
      subgroup was different from the two others.

PMID- 9629948
TI  - Gender differences in patients with bipolar disorder influence outcome in the
      medical outcomes survey (SF-20) subscale scores.
AB  - BACKGROUND: The importance of gender on the course and outcome in bipolar
      disorder (BD) has been widely acknowledged. The limited data suggest that the
      prevalence is similar between sexes but that the course of illness may be
      different. This study investigated gender differences in a clinic sample of
      patients with BD including a measure of subjects' perception of well-being and
      functioning. METHODS: Euthymic outpatients attending a mood disorders clinic were
      systematically assessed. Measurements obtained included SADS-LV, Hamilton
      Depression Ratings scores, Young Mania Rating scores, and Medical Outcome Survey
      Short Form 20 items and Global Assessment of Functioning. RESULTS: Women with BD
      have a later onset of mania, are more likely to have a rapid cycling course,
      experience mixed episodes, experience more depressive episodes and report more
      overall impairment in all MOS subscale scores with significant impairment in
      physical health and pain. CONCLUSIONS: Further investigation and replication of
      these differences need to be addressed including non-euthymic patients and during
      a longer period of systematic follow-up.

PMID- 9629949
TI  - Comorbid depressive disorder increases vulnerability to the 35% carbon dioxide
      (CO2) challenge in panic disorder patients.
AB  - BACKGROUND: The hypothesis of this study was that panic disorder patients with a
      comorbid depressive disorder would be less vulnerable to the 35% CO2 panic
      provocation challenge than panic disorder patients without a comorbid depressive
      disorder. This hypothesis was based on findings from ventilatory response studies
      in depressive patients. METHODS: Twelve panic disorder patients with and 23 panic
      disorder patients without a comorbid depressive disorder were challenged.
      RESULTS: Panic disorder patients with a comorbid depressive disorder scored
      significantly higher on ratings of subjective anxiety and panic symptoms induced
      by the challenge. CONCLUSIONS: A comorbid depressive disorder appeared to
      increase the vulnerability of panic disorder patients to this panic provocation.
      LIMITATION: We did find significant differences, but these differences did not
      confirm the original hypothesis. CLINICAL RELEVANCE: Our results support clinical
      data that show that a comorbid depressive disorder correlates with an increased
      severity of panic disorder.

PMID- 9629950
TI  - A double-blind double-dummy study of citalopram comparing infusion versus oral
      administration.
AB  - BACKGROUND: This study compares antidepressant efficacy and tolerability of
      citalopram given either orally or as a slow drop infusion. METHODS: Citalopram
      (40 mg/day) was administered double-blindly as tablets or slow-drop infusion
      during the first 10 days and then open, orally, up to treatment Day 42. RESULTS:
      In 60 moderately to severely depressed patients, the Hamilton depression total
      score (17-items) at baseline was 23.9 and 23.6 in the active infusion (n = 30)
      and active tablet (n = 30) group, respectively. These scores dropped in both
      groups to 15.6 and 16.9 on Day 10, and to 10.3 and 10.2 on Day 42. Response rates
      (delta Hamilton > or = 50%) amounted to 33.3% and 17.9% on Day 10, and 66.2% and
      63.3% on Day 42, without a relevant group difference in citalopram plasma
      concentration. CONCLUSION: Slow-drop infusion with citalopram shows a similar
      risk/benefit relationship to oral citalopram. The design of this study allowed us
      to evaluate pharmacological but not psychological factors which may contribute to
      response to slow-drop infusion.

PMID- 9629951
TI  - The inflammatory response system and the availability of plasma tryptophan in
      patients with primary sleep disorders and major depression.
AB  - BACKGROUND: It is now well established that major depression is accompanied by an
      immune-inflammatory system response and that indicators of the latter are
      inversely correlated with lower availability of plasma tryptophan in depression.
      Inflammation and infection can alter sleep architecture, whereas sleep
      disturbances can impair immune functions. AIMS AND METHODS: The aims of the
      present study were to examine: (i) immune-inflammatory markers, i.e. serum
      interleukin-6 (IL-6), IL-8, IL-6 receptor (IL-6R), IL-1R antagonist (IL-1RA),
      gp130, and prostaglandin E2 (PGE2) production by mitogen-stimulated whole blood
      and the availability of plasma tryptophan in patients with primary sleep
      disorders, major depression and healthy volunteers; and (ii) the relationships
      between the availability of tryptophan and indicators of the immune-inflammatory
      response system. RESULTS: Mitogen-stimulated release of PGE2, and serum IL-6 and
      IL-8, were significantly increased in both depressed and sleep disordered
      patients compared to normal controls. Serum IL-1RA was significantly higher in
      depressed patients than in normal controls. Patients with depression and sleep
      disorders had a significantly lower availability of tryptophan than normal
      controls. There were significant and inverse relationships between the
      availability of plasma tryptophan and serum IL-1RA, IL-6 and IL-8. CONCLUSIONS:
      The results suggest that (i) there is an activation of the immune-inflammatory
      response system in primary sleep disorders and depression; and (ii) the decreased
      availability of plasma tryptophan may be related to the inflammatory system
      response.

PMID- 9629952
TI  - Sleep cluster arousal analysis and treatment response to heterocyclic
      antidepressants in patients with major depression.
AB  - BACKGROUND: A close link between sleep normalisation and antidepressant response
      in depressed patients has been reported. We attempt to separate early
      antidepressant treatment responders from nonresponders by the use of sleep EEG
      recordings. METHODS: Sleep EEG recordings were performed in 20 inpatients with a
      unipolar major depressive disorder during the first and third week of treatment
      with heterocyclic antidepressants. Acute treatment polygraphic measures with
      microarousal analysis were used to predict response. Response was defined as a
      minimum reduction of > or = 30% in the v. Zerssen Depression Scale after 3 weeks.
      RESULTS: Compared to the 11 nonresponders, the 9 responders initially showed a
      highly significant increase of arousals during sleep quantified with the cluster
      disturbed sleep (CDS), whereas the classical sleep parameters (REM, stage I-IV)
      had no predictive value. CONCLUSIONS: The validity of our results is limited by
      the small number of patients and the lacking randomised assignment. Nevertheless
      the results are still interesting. Because the CDS clearly separated responders
      from nonresponders at treatment onset. This could be due to a different
      reagibility of the catecholaminergic system. The data indicate that the CDS can
      be helpful for the prediction of early antidepressant treatment response.

PMID- 9629953
TI  - Clinical experience using gabapentin adjunctively in patients with a history of
      mania or hypomania.
AB  - BACKGROUND: Gabapentin is an anticonvulsant proposed to have mood-stabilizing
      properties. It has been effective in the add-on treatment of refractory partial
      seizures and secondary generalized tonic-clonic seizures. It has the advantage of
      a favorable side effect profile and lack of drug interactions. METHODS: Twelve
      consecutive outpatients with persistent, treatment-resistant bipolar spectrum
      disorders were treated with gabapentin in combination with other medications.
      Patients were started at 300 mg/day, which was titrated according to clinical
      response. Response was assessed every 3-4 weeks with a Clinical Global
      Improvement Scale. Dosage and side effects were noted. The median peak dose was
      2400 mg/day. RESULTS: One patient had a marked response to gabapentin; seven, a
      moderate response; two, mild; and two, no response to treatment. Six patients
      discontinued treatment due to somatic complaints (i.e., sedation or fatigue). The
      most frequently reported adverse effect was sedation. LIMITATIONS: Gabapentin was
      added openly, and rating was nonblind in this case series. The use of concomitant
      medications could have increased the amount of sedation experienced with
      gabapentin. CONCLUSION: Overall, gabapentin was associated with moderate
      improvement of mood symptoms. Given the severity and chronicity of these
      patients' illness, a moderate response must be considered a relative success.
      Controlled studies of gabapentin are needed to clarify its role in the treatment
      of bipolar disorder.

PMID- 9629954
TI  - Should thyroid augmentation precede lithium augmentation--a pilot study.
AB  - BACKGROUND: It has not been investigated whether thyroid augmentation should
      precede lithium augmentation or vice versa. METHODS: In 22 outpatients with major
      depression not responsive to 4 weeks of antidepressant treatment, the effect of
      subsequent 4 weeks of thyroxine administration followed by 4 weeks of lithium
      augmentation was compared with the effect of the same treatments in reverse
      order. RESULTS: The percentage reduction in MADRS score was significantly greater
      in patients who started on thyroxine. CONCLUSIONS: Thyroxine augmentation should
      precede lithium augmentation. LIMITATIONS: We used relatively small doses of
      lithium. CLINICAL RELEVANCE: Thyroxine is effective in augmenting antidepressant
      responses.

PMID- 9629955
TI  - Why Van der Does, Van Dyck and Spinhoven (1997) did not demonstrate that superior
      heartbeat perception in panic disorder is partly an artefact.

PMID- 9629956
TI  - Gating of somatosensory evoked potentials during voluntary movement of the lower
      limb in man.
AB  - Somatosensory evoked potentials (SEPs) evoked by stimulation of the tibial nerve
      (TN) in the popliteal fossa, the sural nerve (Sur) at the lateral malleole, and
      an Achilles tendon (Achilles) tap were recorded before and during voluntary
      plantarflexion, dorsiflexion, and cocontraction of the ipsi- and contralateral
      foot in normal subjects. Suppression (gating) of the TN-SEP began around 60 ms
      before the onset of electromyographic activity (EMG), and became maximal 50-100
      ms after the onset of EMG. Similar gating was observed for the SEP evoked by
      activation of muscle afferents (Achilles) and cutaneous afferents (Sur). The TN
      SEP was similarly depressed at the onset of a plantarflexion as at the onset of
      dorsiflexion. A depression, although much smaller, was also observed at the onset
      of movement of the contralateral limb. The depression of the TN-SEP after the
      onset of EMG decreased when fast-conducting afferents were blocked by ischemia
      below the knee joint. The TN-SEP was equally depressed during tonic dorsiflexion,
      plantar-flexion, and cocontraction of dorsi- and plantarflexors. The TN-SEP was
      depressed for up to 300 ms when preceded by stimulation of Sur or a biceps
      femoris tendon tap. Gating of lower limb SEPs thus appears to have both central
      and peripheral components of which neither seems to be specific for the muscle
      being contracted or the sensory afferents being stimulated. We encourage that
      caution is taken when drawing functional conclusions regarding movement-specific
      modulation of afferent inflow to the somatosensory cortex based on observations
      of gating of lower limb SEP.

PMID- 9629957
TI  - The corticostriatal system mediates the "paradoxical" contraversive rotation but
      not the striatal hyperexpression of Fos induced by amphetamine early after 6
      hydroxydopamine lesion of the nigrostriatal pathway.
AB  - In rats with unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal
      pathway, amphetamine produces ipsiversive rotational behavior and activation of
      Fos in the intact striatum, but practically no activation of Fos in the
      denervated striatum. However, a seemingly paradoxical contraversive rotation,
      accompanied by intense striatal Fos activation in the lesioned striatum, has been
      observed during the first few days postlesion. In the present work, behavioral
      tests and immunohistochemistry for Fos protein and tyrosine hydroxylase (TH) were
      combined to study striatal changes 36 h after 6-OHDA lesion and particularly the
      possible involvement of glutamatergic corticostriatal afferents. Injection of
      amphetamine (0.5 mg/kg or 5 mg/kg) induced contraversive rotation and strong and
      evenly distributed Fos expression in the lesioned striatum; in the contralateral
      striatum, however, Fos density was lower than in nonlesioned rats. Pretreatment
      with the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist MK-801 (either
      0.5 mg/kg or 5 mg/kg) did not significantly affect the hyperexpression of Fos in
      the lesioned striatum, but suppressed the contraversive rotation. Similarly, rats
      that were subjected to corticostriatal deafferentation (confirmed by sensory
      neglect tests) and 6-OHDA lesion (1 week or 3 weeks later) showed no significant
      reduction in the striatal Fos hyperexpression induced by amphetamine (0.5 mg/kg
      or 5 mg/kg) and no significant rotational asymmetry. In conclusion, the present
      results indicate that glutamatergic corticostriatal afferents are essential for
      the contraversive rotational behavior but not the striatal hyperexpression of Fos
      observed in response to amphetamine early after 6-OHDA lesion, and suggest that
      intense dopaminergic stimulation of striatal neurons is sufficient for induction
      of Fos, but that concurrent glutamatergic stimulation is necessary for the motor
      response.

PMID- 9629958
TI  - The paraventricular nucleus of the hypothalamus sends efferents to the spinal
      cord of the rat that closely appose sympathetic preganglionic neurones projecting
      to the stellate ganglion.
AB  - Using a combination of anterograde and retrograde neuronal tract-tracing
      techniques, the descending projections from the paraventricular nucleus of the
      hypothalamus (PVN) to the brain/spinal cord and in particular those axonal
      projections that appear to be contiguous with sympathetic preganglionic neurones
      (SPN) projecting to the stellate ganglion have been studied. Descending PVN
      pathways were located by the anterograde transport of biotinylated dextran amine
      (BDA), whilst SPN were retrogradely labelled with cholera B toxin subunit
      conjugated to horseradish peroxidase (CB-HRP). BDA-labelled PVN axons terminated
      in both hypothalamic and extrahypothalamic (including the midbrain, medulla and
      spinal cord) brain nuclei, with dense terminal labelling observed particularly in
      the arcuate hypothalamic nucleus and adjacent median eminence, in the solitary
      tract, vagal nuclei and in the intermediolateral region of the spinal cord (IML).
      Varicose descending PVN fibres in the IML were often observed to closely appose
      both the cell soma and dendrites of retrogradely labelled SPN (projecting to the
      stellate ganglion) in the spinal cord. In addition, it was shown that PVN
      descending axons crossing to the contralateral side of the spinal cord were
      closely associated with retrogradely labelled SPN projecting to the superior
      cervical ganglion. Such findings suggest that descending pathways from the PVN
      may exhibit a direct influence on cardiac sympathetic outflow and may also
      influence the behaviour of the contralateral population of SPN projecting to the
      superior cervical ganglion.

PMID- 9629959
TI  - Effects of anterior cingulate cortex lesions on ocular saccades in humans.
AB  - Cerebral blood flow studies in humans suggest that the anterior cingulate cortex
      (ACC) could be involved in eye movement control. In two patients with a small
      infarction affecting the posterior part of this area (on the right side) and in
      ten control subjects, we studied several paradigms of saccadic eye movements: gap
      task, overlap task, antisaccades (using either a 5 degrees or 25 degrees lateral
      target), memory-guided saccades with a short (1 s) or long (7 s) delay, and
      sequences of memory-guided saccades. Compared with controls, patients had normal
      latency in the gap task but increased latency in the other tasks. The gain of
      memory-guided saccades was markedly decreased, bilaterally, whatever the duration
      of the delay. Patients made more errors than controls in the antisaccade task
      when the 5 degrees lateral target was used, and a higher percentage of
      chronological errors in the sequences of saccades. These results show that the
      posterior part of the right ACC plays an important role in eye movement control
      and suggest that this area could correspond to a "cingulate eye field" (CEF). The
      role of this hypothetical CEF could be an early activation exerted on the frontal
      ocular motor areas involved in intentional saccades and also a direct action on
      brainstem ocular premotor structures.

PMID- 9629960
TI  - Context-specific short-term adaptation of the phase of the vestibulo-ocular
      reflex.
AB  - The phase of the angular vestibulo-ocular reflex (VOR) is subject to adaptive
      control. We had previously found that adapting the phase of the VOR also produced
      changes in drift on eccentric gaze-holding, implying a change in the time
      constant of the velocity-to-position neural integrator. Here we attempted to
      dissociate changes in gaze-holding drift from changes in the phase of the VOR. In
      normal human subjects, for 2 h, we alternated 5 min of VOR phase adaptation
      (sinusoids, 0.2 Hz) with 5 min of making saccades in the light with the head
      stationary. Afterwards, changes in VOR phase were the same (32% of requested) as
      those obtained with 1 h of phase adaptation alone, but changes in drift following
      saccades were much smaller than those found after phase adaptation alone (0.8
      degrees/s compared with 5 degrees/s). When measuring drift after VOR steps,
      however, the changes were closer to those found after phase adaptation alone (3.8
      degrees/s). To test the relationship between gaze-holding drift after VOR steps
      and adaptive changes in VOR phase, we alternated sinusoidal VOR phase adaptation
      with normal VOR steps in the light. In this paradigm, the adaptive change in VOR
      phase was about the same as with phase-adaptation alone (35%), but there was now
      little drift after saccades (1.9 degrees/s) or after VOR steps (0.7 degrees/s).
      We conclude that the state of the velocity-to-position neural integrator can be
      altered selectively and rapidly depending upon the task required. Such context
      specific adaptation is advantageous, because it allows adjustment of the phase of
      the VOR without degrading the ability to hold eccentric fixation.

PMID- 9629961
TI  - Time course of changes in EMG activity of fast muscles after partial denervation.
AB  - After partial denervation, the remaining motor units (MUs) of adult fast extensor
      digitorum longus muscle (EDL) expand their peripheral field. The time course of
      this event was studied using tension measurement and recordings of
      electromyographic (EMG) activity. The results show that after section of the L4
      spinal nerve, when only 5.3 +/- 0.63 of the 40 MUs normally supplying EDL muscle
      remain, the force of individual motor units starts to increase between the 1st
      and 2nd week after the operation and continues to do so for a further week. The
      drastic reduction of the number of motoneurones supplying the fast EDL leads to
      an increase in activity of the remaining MUs. In the 1st week after partial
      denervation, there was a sharp increase in the EMG activity of remaining motor
      units. During the next 12 days, this increase became less marked, but EMG
      activity remained nevertheless significantly higher than that of the unoperated
      EDL muscle. Many MUs became tonically active during posture. The EMG activity
      pattern during locomotion was also altered, so that the burst duration was
      positively correlated with the step cycle duration. Moreover, shortly after
      partial denervation, the interlimb coordination was disturbed but returned to its
      original symmetrical use 1-2 weeks later.

PMID- 9629962
TI  - Postural adjustments accompanying fast pointing movements in standing, sitting
      and lying adults.
AB  - The present study evaluated the effect of different positions, which varied in
      the amount of bodily support, on postural control during fast pointing movements.
      Fourteen adult subjects were studied in standing, various sitting and lying
      positions. Multiple surface electromyograms (EMGs) of arm, neck, trunk and upper
      leg muscles and kinematics were recorded during a standard series of unilateral
      arm movements. Two additional series, consisting of bilateral arm movements and
      unilateral arm movements with an additional weight, were performed to assess
      whether additional task-load affected postural adjustments differently in a
      sitting and standing position. Two pointing strategies were used--despite
      identical instructions. Seven subjects showed an elbow extension throughout the
      movements. They used the deltoid (DE) as the prime mover (DE group). The other
      seven subjects performed the movement with a slight elbow flexion and used the
      biceps brachii (BB) as the prime mover (BB group). The two strategies had a
      differential effect on the postural adjustments: postural activity was less and
      substantially later in the BB-group than in the DE group. Anticipatory postural
      muscle activity was only present in the DE group during stance. In all positions
      and task-load conditions the dorsal postural muscles were activated before their
      ventral antagonists. The activation rate, the timing and--to a lesser extent the
      amplitude of the dorsal muscle activity was position dependent. The position
      dependency was mainly found in the caudally located lumbar extensor (LE) and
      hamstrings (HAM) muscles. The EMG amplitude of LE and HAM was also affected by
      body geometry (trunk and pelvis position). Position and body geometry had only a
      minor effect on the activity of the neck and thoracic extensor muscles. This
      difference in behaviour of lower and upper postural muscles suggests that they
      could serve different postural tasks: the lower muscles being more involved in
      keeping the centre of mass within the limits of the support surface, and the
      upper ones in counteracting the reaction forces generated by movement onset.
      Increasing task-load by performing bilateral movements and--to a minor extent-
      during loaded unilateral movements affected the temporal and quantitative
      characteristics of the postural adjustments during standing and sitting in a
      similar way. The effect was present mainly during the early part of the response
      (within 100 ms after prime mover onset). This suggests that feedforward or
      anticipatory mechanisms play a major role in the task-specific modulation of
      postural adjustments.

PMID- 9629963
TI  - The influence of stimulus shape on orientation acuity.
AB  - Orientation acuity was estimated for vertical and oblique bar stimuli.
      Discrimination thresholds were affected by changes in the length and width of the
      targets, falling as bar length was increased and, conversely, rising as the bars
      were made wider. These changes are complimentary, in that overall discrimination
      performance can be predicted by a single measure of the orientation "entropy" of
      the target, namely the height-to-width ratio. The data provide support for a
      model of orientation coding where discrimination performance is not simply a
      reflection of the signal-to-noise ratio in single cells in the striate cortex.

PMID- 9629964
TI  - Intracortical connections between motor cortical zones controlling antagonistic
      muscles in the cat: a combined anatomical and physiological study.
AB  - Experiments were done on nine cats anaesthetized with pentobarbitone to determine
      whether motor cortical zones controlling antagonistic muscles are synaptically
      interconnected. Motor cortical zones controlling wrist flexors, or extensors,
      were identified by microstimulation and intramuscular electromyographic
      recordings (microstimulation: 11 pulses at 333 pulses/s, current 10-40 microA).
      The position of each zone of interest was marked by a small ink spot on the
      surface of the cortex and on a scaled drawing of the cortical surface (cruciate
      region). Following the identification of wrist flexor and extensor zones the
      anterograde tracer biocytin was injected into one, or two, wrist extensor zones
      at three depths (400, 800 and 1500 microm) from the cortical surface. A small
      injection of horseradish peroxidase (HRP)--producing a dark brown spot of
      approximately 300-500 microm--was made in layer II-III of one or more wrist
      flexor zones. Similar HRP injections were made in the deep layers of wrist
      extensor zones that were not labelled by biocytin. The HRP injections served to
      mark the position of potential targets of biocytin-labelled fibres. In some
      experiments the biocytin was injected into a wrist flexor zone and HRP was
      deposited in one or more wrist extensor zones. Biocytin-labelled fibres (blue)
      were found throughout the expanse of the forelimb representation zone, as has
      been previously reported. More specifically, in all animals biocytin-labelled
      fibres were found in identified cortical zones controlling the same muscle(s) as
      well as in zones controlling an antagonist(s). Club-like swellings, indicative of
      synaptic boutons, were observed on these fibres. The density of labelled fibres
      was greater in the upper cortical layers (II-III), but a large number of
      terminals were also present in the lower cortical layers (V-VI). We conclude that
      there exist intracortical circuits linking motor cortical zones controlling
      antagonistic muscles. Elucidating the nature and function of these circuits is
      likely to be important for understanding the mode of operation of the motor
      cortex.

PMID- 9629965
TI  - The representation of gravitational force during drawing movements of the arm.
AB  - The purpose of the present experiment was to study the way in which the central
      nervous system (CNS) represents gravitational force (GF) during vertical drawing
      movements of the arm. Movements in four different directions: (a) upward vertical
      (0 degrees), (b) upward oblique (45 degrees), (c) downward vertical (180 degrees)
      and (d) downward oblique (135 degrees), and at two different speeds, normal and
      fast, were executed by nine subjects. Data analysis focused upon arm movement
      kinematics in the frontal plane and gravitational torques (GTs) exerted around
      the shoulder joint. Regardless of movement direction, subjects showed straight
      line paths for both speed conditions. In addition, movement time and peak
      velocity were not affected by movement direction and consequently changes in GT,
      for both speeds tested. Movement timing (evaluated through the ratio of
      acceleration time to total time) changed significantly, however, as a function of
      movement direction and speed. Upward movements showed shorter acceleration times
      when compared with downward movements. Concerning the four directions, movements
      made at 0 degrees and 45 degrees differed significantly from those made at 135
      degrees and 180 degrees. Drawing movements executed at rapid speed presented
      similar acceleration and deceleration times compared with movements executed at
      normal speed, which showed greater acceleration than deceleration times. In
      addition, the form of velocity profiles (assessed through the ratio of maximum to
      mean velocities), was significantly modified only with movement speed. Results
      from the present study suggest that GF is efficiently incorporated into internal
      dynamic models that the brain builds up for the execution of arm movements.
      Furthermore, it seems that GF not only is a mechanical parameter to be overcome
      by the motor system but also constitutes a reference (vertical direction), both
      of which are represented by the CNS during inverse kinematic and dynamic
      processes.

PMID- 9629966
TI  - The effects of competition and motor reprogramming on visuomotor selection in
      unilateral neglect.
AB  - Patients with unilateral neglect following right hemisphere damage may have
      difficulty in moving towards contralesional targets. To test the hypothesis that
      this impairment arises from competing motor programs triggered by irrelevant
      ipsilesional stimuli, we examined 16 right hemisphere patients, eight with left
      visual neglect and eight without, in addition to eight healthy control subjects.
      In experiment 1 subjects performed sequences of movements using their right hand
      to targets on the contralesional or ipsilesional side of the responding limb. The
      locations of successive targets in each sequence were either predictable or
      unpredictable. In separate blocks of trials, targets appeared either alone or
      with a simultaneous distractor located at the immediately preceding target
      location. Neglect patients were significantly slower to execute movements to
      contralesional targets, but only for unpredictable movements and in the presence
      of a concurrent ipsilesional distractor. In contrast, healthy controls and right
      hemisphere patients without neglect showed no directional asymmetries of movement
      execution. In experiment 2 subjects were required to interrupt a predictable,
      reciprocating sequence of leftward and rightward movements in order to move to an
      occasional, unpredictable target that occurred either in the direction opposite
      to that expected, or in the same direction but twice the extent. Neglect patients
      were significantly slower in reprogramming the direction and extent of movements
      towards contralesional versus ipsilesional targets, and they also made
      significantly more errors when executing such movements. Right hemisphere
      patients without neglect showed a similar bias in reprogramming direction (but
      not extent) for contralesional targets, whereas healthy controls showed no
      directional asymmetry in either condition. On the basis of these findings we
      propose that neglect involves a competitive bias in favour of motor programs for
      actions directed towards ipsilesional versus contralesional events. We suggest
      that programming errors and increased latencies for contralesional movements
      arise because the damaged right hemisphere can no longer effectively inhibit the
      release of inappropriate motor programs towards ipsilesional events.

PMID- 9629967
TI  - Cooperative interaction among the various regulatory sites within the NMDA
      receptor-channel complex in modulating the evoked responses to noxious thermal
      stimuli of spinal dorsal horn neurons in the cat.
AB  - Interactions among antagonists acting at different regulatory sites within the N
      methyl-D-aspartate (NMDA) receptor-channel complex on the evoked responses to
      noxious thermal stimuli of wide dynamic range (WDR) neurons in spinal dorsal horn
      were studied on 21 adult anesthetized and spinalized cats. The responses of
      nociceptive spinal dorsal horn neurons to noxious heating (45-55 degrees C) of
      the glabrous skin of the unilateral hind paw were reduced markedly by
      iontophoretically applied antagonists. The specific recognition site antagonist,
      DL-2-amino-5-phosphonovaleratic acid (APV), the strychnine-insensitive glycine
      site antagonist 7-chlorokynurenic acid (7CKA), the polyamine site antagonist
      ifenprodil (IFEN), and the phencyclidine (PCP) site antagonists ketamine (KET)
      and MK-801 (40-100 nA) significantly reduced (t-tests, P < 0.01) the noxious
      thermal stimulus-evoked responses in about 70% of the neurons by (mean +/- SE)
      54.1 +/- 5.8% (n = 19), 80.8 +/- 4.7% (n = 16), 51.1 +/- 6.4% (n = 10), 77 +/-
      4.9% (n = 16) and 81.2 +/- 8.1% (n = 5), respectively. APV and IFEN were less
      effective in blocking noxious thermal stimuli-evoked responses than 7CKA, KET and
      MK-801 (ANOVA, P < 0.05). The responses were completely inhibited in some
      neurons. After co-administration of the antagonists, APV + 7CKA, APV + IFEN, 7CKA
      + IFEN, APV + KET and APV + MK-801, all at the subthreshold ejection current, the
      responses were reduced markedly in 13 of 16, 7 of 10, 5 of 10, 3 of 6 and 3 of 5
      neurons, respectively. The present study suggests that blockage of any component
      of the NMDA receptor-channel complex antagonizes the NMDA receptor-mediated
      response, and that there are the cooperative interactions among the various
      regulatory sites within the NMDA receptor-channel complex in the transmission or
      modulation of spinal nociceptive thermal information.

PMID- 9629968
TI  - The mode of movement selection. Movement-related cortical potentials prior to
      freely selected and repetitive movements.
AB  - In two previous studies, the readiness potential (RP) has been reported to be
      influenced by the mode of movement selection. Freely selected movements were
      found to have a higher RP amplitude than fixed repetitive movements. This was
      attributed to the higher demands on planning for the performance of freely
      selected movements. However, movements in the free mode are distinct from
      movements in the fixed mode in more than one respect. For example, they are also
      associated with a higher degree of alteration of the side and/or the finger of
      movement execution and hence serial "novelty" across blocks of trials. The aim of
      our study was to establish whether the greater novelty of movements in the free
      mode could also contribute to the enhanced RP amplitude of movements in the free
      mode of movement selection by comparing free versus fixed movements performed in
      long and short sequences that differ in terms of serial novelty. The RP was
      recorded in 31 healthy young subjects with electrodes placed over Fz, C3, Cz, C4
      and Pz. Two types of movement were studied: randomly chosen button presses with
      right or left index or middle finger (free mode), and repetitive pressing of a
      predetermined button (fixed mode). We found that: (1) in confirmation of previous
      studies, the amplitude of the RP was higher for freely selected than free
      movements; (2) the effect of the mode of movement selection was present over
      central electrodes but was most pronounced for parietal electrode Pz, with
      movements in the free mode showing the earliest and greatest increase in
      negativity at this site; (3) this parietally enhanced negativity in free compared
      with the fixed mode was absent after the subjects had performed a block of long
      movement sequences, suggesting that serial novelty of movements also contributed
      to the effect of mode on the RP amplitude; (4) both the latency and the magnitude
      of the lateralized readiness potential (LRP) were altered by the mode of movement
      selection. Movements in the free mode showed an earlier onset of the LRP, which
      had a higher peak than the LRP prior to movements in the fixed mode. This effect
      was mainly due to an increased amplitude of the RP over the electrode
      contralateral to the side of movement prior to freely selected movements. These
      findings are discussed in relation to previous RP and positron emission
      tomography studies.

PMID- 9629969
TI  - Acinetobacter species as nosocomial pathogens.

PMID- 9629970
TI  - Low specificity of the bacterial index for the diagnosis of bacterial pneumonia
      by bronchoalveolar lavage.
AB  - The bacterial index (BI) as defined by the sum of log10 colony-forming units
      (cfu) of microorganisms per milliliter of bronchoalveolar lavage (BAL) fluid,
      i.e., a multiplication of the single cfu/ml, has been used to distinguish between
      polymicrobial pneumonia (BI> or =5) and colonization (BI<5). Since many false
      positive results are to be expected using this parameter, the diagnostic value of
      the BI was studied prospectively by obtaining bacteriologic cultures of BAL fluid
      in 165 consecutive unselected patients. In 27 cases the diagnosis of bacterial
      pneumonia was established on clinical criteria. In 133 patients pneumonia could
      be excluded, and in five patients the diagnosis remained unclear. Using a cut-off
      of > or = 10(5) cfu/ml BAL fluid, sensitivity and specificity for the diagnosis
      of pneumonia were 33% (9/27) and 99% (132/133), respectively. Sensitivity was
      mainly influenced by prior treatment with antibiotics, being 70% (7/10) in
      untreated and 12% (2/17) in treated patients. Applying the BI methodology at a
      cut-off of > or =5, however, resulted in an unacceptably high rate of 16
      additional false-positive results, thus lowering the specificity to 87% (116/133;
      P<0.0001) while increasing the sensitivity to only 41% (11/27; P = 0.77). In
      conclusion, given the high rate of false-positive results, the methodology of the
      BI is of doubtful value for the diagnosis of bacterial pneumonia by BAL in an
      unselected patient group. By applying the absolute number of cfu/ml BAL fluid,
      however, positive bacteriologic cultures of BAL fluid are highly specific for the
      diagnosis of pneumonia. Their sensitivity is limited by previous antibiotic
      therapy.

PMID- 9629971
TI  - Increasing incidence of meningococcal disease in Spain associated with a new
      variant of serogroup C.
AB  - Serogroup B has been the main cause of meningococcal disease in Spain since at
      least 1979, but in recent years an increase in the prevalence of infection due to
      serogroup C meningococci has been detected. In 1996, for the first time, most
      cases of meningococcal disease were caused by serogroup C strains. The
      sero/subtype of all serogroup C meningococci received from 1993 to June 1996 was
      determined, and the results showed that C:2b:P1.2,5, the most common phenotype in
      1995 and 1996 (63% and 65%, respectively), represented only 4.8% of strains in
      1993. The C:2b: P1.2,5 epidemic strains appear to be responsible for the high
      prevalence of serogroup C in Spain. One hundred fifty-one randomly selected
      serogroup C strains were analyzed by multilocus enzyme electrophoresis,
      ribotyping, and pulsed-field gel electrophoresis. Pulsed-field gel
      electrophoresis provided the most accurate information: more than 80% of the
      C:2b:P1.2,5 and C:2b:P1.2 isolates exhibited one of two very closely related
      profiles, while most of the C:2b:NST and C:2b:P1.5 strains had a pattern located
      at a genetic distance of 0.24 from those two profiles. The results show that
      C:2b:P1.2,5 strains represent a subclone or a genetic variant of the previously
      identified Spanish epidemic clone C:2b:non-subtypable strains.

PMID- 9629972
TI  - Rate of infection of Ixodes ricinus ticks with Borrelia burgdorferi sensu
      stricto, Borrelia garinii, Borrelia afzelii and group VS116 in an endemic focus
      of Lyme disease in Italy.
AB  - A study to evaluate the natural rate of infection of Ixodes ricinus with Borrelia
      burgdorferi sensu lato was carried out in an endemic focus of Lyme disease in the
      Trieste area in northern Italy. Two-hundred and twenty-seven ticks collected in
      ten different stations were tested individually for the presence of the
      spirochetes using polymerase chain reaction techniques able to identify both
      Borrelia burgdorferi sensu lato and the four genospecies (Borrelia burgdorferi
      sensu stricto, Borrelia garinii. Borrelia afzelii and group VS116). Multiple
      infection of individual ticks was found. The infection rate ranged from 0-70%.
      Infection of Ixodes ricinus with Borrelia burgdorferi group VS116 was found for
      the first time in Italy in both a high and a low endemic focus of Lyme disease.

PMID- 9629973
TI  - First isolation of Rickettsia helvetica from Ixodes ricinus ticks in France.
AB  - Two rickettsial isolates recovered from Ixodes ricinus ticks in Puy-de-Dome
      (Central France) were characterized by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis, Western blot immunoassay, restriction fragment length
      polymorphism analysis, and sequencing of a portion of the citrate-synthase gene.
      By these methods, the isolates appeared to be identical to a member of the
      spotted fever group rickettsiae, Rickettsia helvetica. This first isolation of
      Rickettsia helvetica in France has epidemiologic importance; a serosurvey on
      Mediterranean spotted fever conducted previously in Puy-de-Dome, where the
      infection is not endemic, demonstrated a high seroprevalence of nonspecific
      antibodies directed against spotted fever group rickettsiae lipopolysaccharides,
      and thus the possibility of infection due to a rickettsia different from
      Rickettsia conorii was suggested. The isolation of Rickettsia helvetica in
      anthropophilic ticks in the same area further supports this hypothesis.

PMID- 9629974
TI  - Necrotizing fasciitis caused by Staphylococcus aureus.
AB  - Two patients with rapidly progressive necrotizing fasciitis of a lower extremity
      due to Staphylococcus aureus as a single pathogen are described. In both patients
      the portal of entry was attributed to needle puncture (intra-articular injection
      and intravenous catheter, respectively), followed by bacteremia. Necrotizing
      fasciitis occurred in a site remote from the needle puncture, suggesting
      metastatic infection. One patient developed toxic shock syndrome and the other a
      sunburn-like rash and erythematous mucosae with strawberry tongue. One patient
      died, and the other required above-knee amputation due to secondary infectious
      complications. Staphylococcus aureus may mimic the presentation of invasive group
      A streptococcal infections. A history of needle puncture should alert the
      physician to the possibility of Staphylococcus aureus infection.

PMID- 9629975
TI  - Endarteritis and mycotic aortic aneurysm caused by an oral strain of
      Actinobacillus actinomycetemcomitans.
AB  - Actinobacillus actinomycetemcomitans was isolated from blood cultures of a 33
      year-old febrile patient with a previously undiagnosed coarctation of the aorta.
      Subgingival samples from diseased periodontal pockets revealed the presence of A.
      actinomycetemcomitans. An infected (mycotic) aortic aneurysm and endarteritis
      were diagnosed and surgically treated. The identity of blood and oral clinical
      isolates of A. actinomycetemcomitans was supported by genetic analysis, including
      fingerprinting by restriction fragment length polymorphism, ribotyping, and
      random amplified polymorphic DNA; biotyping; and antibiogram typing. These data
      strongly suggest that the periodontal pockets were the primary source of A.
      actinomycetemcomitans endarteritis in this case.

PMID- 9629976
TI  - Use of pulsed field gel electrophoresis to determine the source of microbial
      contamination of central venous catheters.
AB  - Microorganisms detected in situ on the distal tip of central venous catheters
      (CVC) within 90 min of insertion were investigated using pulsed-field gel
      electrophoresis to analyse genomic fragments obtained with the SmaI restriction
      enzyme. Thirty patients received a triple lumen CVC, which was inserted directly
      through the skin using the Seldinger technique. In a further 30 patients a triple
      lumen CVC was inserted through a Swan sheath, thereby avoiding direct contact of
      the CVC with the skin. Staphylococci were isolated from the distal tips of the
      catheters in 6 patients (5 who had the CVC inserted directly through the skin and
      1 who had the CVC inserted via a Swan sheath.) Twenty-three staphylococcal
      isolates were also isolated from the insertion equipment and the skin swabs
      surrounding the insertion site of these six patients. All the isolates were
      genotyped. In one of the patients the organisms isolated from the skin were
      identical to those on the CVC tip. In two further patients similar organisms were
      isolated from the insertion equipment and the patients' skin. These results, in
      addition to the reduced colonisation rates observed when catheters were
      introduced through a Swan sheath, support the hypothesis that microorganisms from
      the skin are impacted onto the CVC tip and the CVC insertion equipment at
      catheter insertion.

PMID- 9629977
TI  - Use of simulated blood cultures to compare a specific fungal medium with a
      standard microorganism medium for yeast detection.
AB  - The aim of this study was to compare the performance of a specific blood culture
      medium recently developed to detect fungi on the Bactec 9240 system (Mycosis
      IC/F; Becton Dickinson Diagnostic Instrument Systems, USA) with that of the
      standard medium used for detection of bacteria (Aerobic Plus/F; Becton
      Dickinson). Simulated blood cultures were performed on 43 strains belonging to
      ten fungal species using the two media. The mean time to yeast detection using
      the Mycosis IC/F medium was 29.03+/-13.99 h, in contrast to a mean time of
      73.92+/-56.74 h using the Aerobic Plus/F medium. These results show that the
      Mycosis IC/F medium clearly reduces the time to yeast detection on the Bactec
      9240.

PMID- 9629978
TI  - Detection of human herpesviruses 6 and 7 in heart transplant recipients by a
      multiplex polymerase chain reaction method.
AB  - In order to evaluate the possible reactivation of human herpesviruses 6 (HHV-6)
      and 7 (HHV-7) after heart transplantation, buffy-coat and plasma specimens from
      21 transplant patients and 56 healthy blood donors were examined for HHV-6 and
      HHV-7 DNA by polymerase chain reaction. Human herpesvirus 6 and HHV-7 infection
      or reactivation has been suggested to play a role in cytomegalovirus disease
      progression in renal transplant recipients. In the present study, however, no
      significant difference in the prevalence of HHV-6 and HHV-7 was found between the
      immunosuppressed and the healthy population; moreover, no viral reactivation was
      found in the heart transplant recipients.

PMID- 9629979
TI  - Diagnosis of herpetic keratoconjunctivitis by nested polymerase chain reaction in
      human tear film.
AB  - A study was performed to evaluate nested PCR (nPCR) versus viral cultures as
      method and tear film versus corneal scrapings as specimen in the diagnosis of
      viral keratoconjunctivitis. Tear film specimens were taken from both eyes and
      corneal scrapings from the affected eye only in 17 patients with suspected viral
      keratoconjunctivitis. In 15 of the 17 patients the viral agent of the infection
      could be detected: 11 patients had herpes simplex virus type 1, two varicella
      zoster virus, one both herpes simplex virus type 1 and varicella-zoster virus,
      and one adenovirus. Overall there was no significant difference between the
      detection rate for corneal scrapings (85%) and tear film (75%). In both types of
      specimens nPCR showed a higher detection rate than viral cultures (corneal
      scrapings: 87.5% vs 31.25%; tear film: 75% vs 12.5%; P 0.05). For the diagnosis
      of keratoconjunctivitis nPCR is superior to viral culture and tear film is an
      adequate sample that is easier to collect, causing the patient less discomfort.

PMID- 9629980
TI  - Diagnosis of cytomegalovirus infection in kidney transplant recipients by a
      quantitative RNA-DNA hybrid capture assay for cytomegalovirus DNA in leukocytes.
AB  - The clinical value of a new RNA-DNA hybridization assay for quantification of
      cytomegalovirus (CMV) DNA in leukocytes [Hybrid Capture CMV DNA Assay (HCA);
      Murex Biotech, UK] was evaluated. The HCA was compared with an assay for CMV pp65
      antigen in leukocytes and an in-house CMV polymerase chain reaction PCR (CMV-PCR)
      on parallel blood samples. The HCA and the CMV-PCR were less sensitive than the
      CMV pp65 assay, but the positive predictive value of all three methods for CMV
      disease was 50% or less. However, when quantitation of viral load by HCA and CMV
      pp65 assay was taken into consideration, both assays were superior to CMV-PCR in
      predicting CMV disease.

PMID- 9629981
TI  - Influenza A outbreak among adolescents in a ski hostel.
AB  - An outbreak of influenza A H3N2 with a high attack rate (49%) and abrupt onset
      (69% became ill within 2 days) occurred among 81 ski school participants who
      stayed in a crowded hostel in Austria in early 1997. Two students were
      hospitalized with pneumonia; one of them died. Cultures of blood and/or
      respiratory secretions from the hospitalized students yielded toxin-producing
      Staphylococcus aureus. Influenza A H3N2 was confirmed serologically in four
      participants, including one surviving hospitalized student, and by polymerase
      chain reaction of lung tissue from the deceased student. This investigation
      demonstrates that influenza can cause an explosive outbreak among skiers in a
      crowded hostel, leading to severe complications among previously healthy
      adolescents.

PMID- 9629982
TI  - Septic shock and multiorganic failure in murine typhus.

PMID- 9629983
TI  - Persistent airway colonization with Alcaligenes xylosoxidans in two brothers with
      cystic fibrosis.

PMID- 9629984
TI  - Prevalence of Borrelia burgdorferi infection in Ixodes ricinus in central Italy.

PMID- 9629985
TI  - Diarrhoea as the first manifestation of brucellosis.

PMID- 9629986
TI  - Antibody reactivity and fecal recovery of bovine immunoglobulins following oral
      administration of a colostrum concentrate from cows (Lactobin) to healthy
      volunteers.
AB  - Using immunoblot techniques, we investigated the immunoglobulin G (IG) reactivity
      present in Lactobin, an immunoglobulin concentrate (prepared from colostrum pools
      from non-immunized cows) against potential pathogenicity factors from Yersinia
      enterocolitica and Campylobacter jejuni. A strong reactivity against Yersinia
      outer proteins (Yops), against the Yersinia adhesin A (Yad A) as well as a high
      reactivity against flagellin and the outer membrane proteins (OMP) of C. jejuni
      was demonstrated. The IgG antibody reactivity against these antigens was also
      assessed in vitro after incubation of IG with stools from healthy adults for
      different time intervals. Minimal loss occurred within 2 hours of incubation at
      37 degrees C and complete loss after 24 hours. In a clinical study stool
      specimens from 8 healthy volunteers were analyzed 1-4 days after oral
      administration of the drug for the presence of bovine IgG and its antibody
      reactivity against Yersinia antigens. Small amounts of the bovine immunoglobulins
      were detected in stools from 3 of the 8 subjects, however, without antibody
      reactivity. Additional pharmacokinetic investigations in patients with
      gastrointestinal diseases are necessary to determine the optimal therapeutic
      regimen for these patients.

PMID- 9629987
TI  - Excretion kinetics of ifosfamide side-chain metabolites in children on continuous
      and short-term infusion.
AB  - Ifosfamide (IFO) requires metabolic activation by hydroxylation of the ring
      system to exert cytotoxic activity. A second metabolic pathway produces the
      cytostatically inactive metabolites 2-dechloroethyl-ifosfamide (2-D-IFO) and 3
      dechloroethyl-ifosfamide (3-D-IFO) under release of chloroacetaldehyde. This side
      chain metabolism has been suggested to be involved in CNS- and renal toxicity.
      The total urinary excretion of ifosfamide and its metabolites was investigated
      during 23 cycles in 22 children at doses ranging from 400 mg/m2 to 3 g/m2. The
      kinetics of the excretion were compared following short-term and continuous
      ifosfamide infusion at a dosage of 3 g/m2. IFO and side-chain metabolites were
      analyzed by gas chromatography, the active metabolites by indirect determination
      of acrolein (ACR) and IFO mustard (IFO-M) with the NBP test. 59+/-15% of the
      applied dose could be recovered in the urine, 23+/-9% as unmetabolized IFO. The
      main metabolite was 3-D-IFO (14+/-4%) followed by isophosphoramide mustard (IFO
      M) (13+/-4%) and 2-D-IFO (8+/-3%). Neither the total amount recovered nor the
      excretion kinetics of ifosfamide and side-chain metabolites showed obvious
      schedule dependency. The excretion kinetics of side-chain metabolites as well as
      unmetabolized IFO were nearly superimposable on short-term and continuous
      infusion. Even after 1-hour infusion there was a lag of 3 - 6 hours until
      dechloroethylation became relevant. Therefore, differences in toxicity and
      efficacy cannot be explained by an influence of the application time on the
      metabolic profile of ifosfamide.

PMID- 9629988
TI  - Pharmacokinetics of ampicillin/sulbactam in patients undergoing spinal
      microneurosurgical procedures.
AB  - The fixed combination of ampicillin (2 g)/sulbactam (1 g) was administered as
      perioperative prophylaxis at induction of anesthesia in 20 patients undergoing
      spinal microneurosurgery. It was noteworthy that after the short infusion
      ampicillin and sulbactam penetrated rapidly from blood into the different tissues
      affected by the surgical procedures. The following mean concentrations were
      measured in tissues: muscle 32.3+/-6.5 mg/kg ampicillin and 18.6+/-2.9 mg/kg
      sulbactam (11.1 min), ligament 39.5+/-11.1 mg/kg ampicillin and 25+/-6.5 mg/kg
      sulbactam (13.8 min), bone 12+/-3.6 mg/kg ampicillin and 7+/-0.8 mg/kg sulbactam
      (20.6 min), disk 10.2+/-3.3 mg/kg ampicillin and 7.3+/-1.8 mg/kg sulbactam (44.2
      min). The mean time of sampling is given in brackets. For a period of at least 2
      h the levels of both drugs measured in serum and in the different tissues were
      above the MICs for bacteria involved in postoperative wound infections. The
      administration of ampicillin/sulbactam apparently achieved sufficiently, high
      antibiotic concentrations, even in bradytrophic tissues such as ligament, bone,
      and disk, and seemed to meet the pharmacological criteria for perioperative
      prophylaxis in spinal microneurosurgery.

PMID- 9629989
TI  - Creatine and caffeine in anaerobic and aerobic exercise: effects on physical
      performance and pharmacokinetic considerations.
AB  - The pharmacokinetics and effects of creatine and caffeine administration on
      anaerobic and aerobic performance of 7 trained athletes were studied in a
      randomized, placebo-controlled, double-blind crossover design. The treatments
      were: placebo (PLA), a single oral dose (7 mg x kg(-1)) of caffeine (CAF),
      repeated oral doses (3 x 100 mg x kg(-1) x day(-1)) of creatine for 3 days (CRE),
      or the combination of caffeine and creatine (CAF + CRE) before physical exercise.
      In one session CAF was administered without exercise. Drug administration was
      followed by 3 repetitive 1-minute exercise bouts on a bicycle ergometer at
      maximal speed (anaerobic exercise) starting 70 min after drug administration.
      Anaerobic exercise was followed by 45 min of cycling at constant pedalling speed
      and workload (aerobic exercise). CRE and CAF, alone or in combination, did not
      improve maximal pedalling speed (rpm), maintenance of maximal speed (rpm) or
      total work output (kJ) during the 1 -minute bouts, when compared with PLA. In
      addition, no statistically significant differences in heart rate or blood lactate
      were observed between the treatments either during anaerobic or aerobic exercise
      bouts. Creatine was rapidly and efficiently absorbed, as reflected by plasma
      concentrations. The mean +/-SEM value for creatine Cmax was 1.22+/-0.14 mmol x l(
      1), tmax 92+/-7 min and plasma half-life (t1/2beta) 172+/-21 min. Caffeine
      pharmacokinetics were not affected by concomitant administration of creatine or
      by physical exercise. In conclusion, neither maximal performance and subsequent
      recovery nor aerobic performance were enhanced by oral creatine supplementation
      in the study.

PMID- 9629991
TI  - Comparative bioavailability of two tablet formulations of ranitidine
      hydrochloride in healthy volunteers.
AB  - This investigation was carried out to evaluate the bioavailability of a new
      tablet formulation of ranitidine HCl (300 mg), Ranid, relative to the reference
      product, Zantac, (300 mg) tablets. The bioavailability was carried out on 24
      healthy male volunteers who received a single dose (300 mg) of the test (T) and
      the reference (R) products in the fasting state, in a randomized balanced 2-way
      crossover design. After dosing, serial blood samples were collected for a period
      of 16 hours. Plasma harvested from blood was analyzed for ranitidine by a
      sensitive and validated high-performance liquid chromatographic assay. The
      maximum plasma concentration (Cmax), area under the plasma concentration time
      curve up to the last measurable concentration (AUC0-t), and to infinity (AUC0
      infinity) and the absorption rate (Cmax/AUC0-infinity) were analyzed
      statistically under the assumption of a multiplicative model. The time to maximum
      concentration (Tmax) was analyzed assuming an additive model. The parametric
      confidence intervals (90%) of the mean values of the pharmacokinetic
      characteristics (AUC0-t, AUC0-infinity), Cmax and Cmax/AUC0-infinity) for T/R
      ratio were in each case well within the bioequivalence acceptable range of 80
      125%. The test formulation was found bioequivalent to the reference formulation
      by the Schuirmann's two one-sided t-tests and by Wilcoxon Mann Whitney two one
      sided tests procedure. Therefore, the 2 formulations were considered to be
      bioequivalent.

PMID- 9629990
TI  - Food interaction pharmacokinetic study of cordaflex 20 mg retard filmtablet in
      healthy volunteers.
AB  - The aim of the present study was to investigate the effect of food consumption on
      the pharmacokinetics of Cordaflex 20 mg retard filmtablet in healthy volunteers
      through measuring nifedipine plasma levels by an HPLC-ED method both after
      fasting and food ingestion. The food interaction pharmacokinetic study of
      Cordaflex 20 mg retard filmtablet was carried out in 12 healthy male volunteers
      treated with a single dose of the preparation both after fasting and after food
      ingestion, in a crossover design allowing 1 week of wash-out period between the 2
      treatments. Nifedipine concentration of plasma samples were determined by an
      isocratic HPLC-ED method [Horvai et al. 1994] with robotic sample processing
      [Horvath et al. 1995, 1996]. The pharmacokinetic parameters (AUC0-infinity, AUC0
      t, Cmax, MRT) were analyzed by calculating 90% confidence interval for
      logarithmic transformed test/reference ratio values, and Schuirmann's statistical
      tests, the tmax and HVD values were analyzed by Wilcoxon's nonparametric
      statistical test. The above statistical tests of the present food interaction
      study indicated significant differences for each one of the respective
      pharmacokinetic parameter pairs calculated for treatments after fasting and after
      food ingestion. On the basis of the above findings and also by comparing the mean
      pharmacokinetic curves, it was evident, that, in agreement with the data of
      literature [Kleinbloesem et al. 1993, Schall et al. 1994], food ingestion
      increased the relative bioavailability and maximum plasma concentration (Cmax).
      Considering the average of the parameter values and also the respective
      statistical tests, it was also apparent that the time to maximum plasma
      concentration (tmax), the mean residence time (MRT), and the half-value duration
      (HVD) all decreased significantly upon the effect of food ingestion.

PMID- 9629992
TI  - Comparative pharmacokinetics and pharmacodynamics of furosemide in Middle Eastern
      and in Asian subjects.
AB  - The pharmacokinetics and pharmacodynamics of a single oral dose of 40 mg
      furosemide has been compared in 11 healthy Middle Eastern Arabs with 12 Asian
      subjects under fasting conditions. There were no significant differences (p >
      0.05) between the 2 ethnic groups in either the area under the plasma
      concentration time curve (AUC) or the time to maximal plasma concentration
      (tmax). The elimination half-life was significantly higher (p < 0.05) in Middle
      Eastern subjects (2.9+/-0.7 h) than in Asian subjects (2.2+/-0.6 h), while the
      maximal plasma concentration (Cmax) in Asian subjects (1,087+/-262 ng/ml) was
      significantly higher (p < 0.05) compared with Middle Eastern Arabs (776+/-163
      ng/ml). The mean residence time (MRT) and the operative apparent volume of
      distribution (Vd/F) were significantly greater in Middle Eastern Arabs (4.5+/-0.9
      h and 54.1+/-14.91) than in Asian subjects (3.6+/-0.8 h and 38.6+/-16.51). The
      difference between them in (Vd/F) abolished (p > 0.05) when corrected for body
      weight. The mean cumulative urinary excretion of furosemide in 8 h was 5.6 mg
      (range 1.6-15.2 mg) for Arabs and 6.1 mg (range 2.1-15.9 mg) for Asians. The
      relationships between furosemide-induced diuresis and furosemide, sodium,
      potassium, calcium, magnesium and chloride excretion rates appeared as a
      clockwise hysteresis loop indicating the development of tolerance during the
      course of drug action in both ethnic groups. No statistically significant
      differences (p > 0.05) were observed in the cumulative amounts excreted in urine
      of these electrolytes or their excretion rates between Arabs and Asians. The
      relationships between urinary excretion rates of sodium, potassium, calcium,
      magnesium, and chloride were linear with almost identical slopes for Arabs and
      Asians in each relationship.

PMID- 9629993
TI  - Bioequivalence evaluation of 2 different oral formulations of ciprofloxacin in
      healthy volunteers.
AB  - A bioequivalence study of 2 oral formulations of 500 mg tablets of ciprofloxacin
      was carried out in 24 healthy volunteers according to a single dose, two
      sequence, crossover randomized design. Blood samples were taken prior to each
      administration and at 13 points within 32 hours after the dose, and plasma
      concentrations of ciprofloxacin were determined by HPLC. The pharmacokinetic
      parameters Cmax and tmax were obtained directly from plasma data, ke was
      estimated by log-linear regression, and AUC was calculated by the trapezoidal
      rule. The pharmacokinetic parameters AUC and Cmax were tested for bioequivalence
      after log-transformation of data, differences of tmax were evaluated
      nonparametrically. The 90% standard confidence intervals of the mean values for
      the test/reference ratios were 0.87-0.97 for AUC and 0.91-1.05 for Cmax, within
      the bioequivalence acceptable range of 0.80-1.25 limits. So, we conclude that
      both formulations were found bioequivalent and, therefore, interchangeable.

PMID- 9629994
TI  - Lack of effect of mizolastine on the safety and pharmacokinetics of digoxin
      administered orally in repeated doses to healthy volunteers.
AB  - The effects of mizolatine, a new H1 receptor antagonist, on safety and
      pharmacokinetics of digoxin were studied in a double-blind placebo-controlled
      crossover study. After administration of digoxine alone (0.25 mg o.d. for 7
      days), 12 healthy young male volunteers (23+/-2 years) received either placebo
      and digoxin (0.25 mg o.d.) or mizolastine (10 mg o.d.) and digoxin (0.25 mg o.d.)
      during 7 days. The assessment criteria consisted in hemodynamic and ECG
      parameters recordings and the pharmacokinetics of digoxin during the last day of
      coadministration (day 14). No difference between the 2 treatment groups was
      evidenced on ECG, hemodynamic, and clinical and laboratory safety parameters. No
      change in AUC and tmax was recorded. No clinically relevant effect of mizolastine
      on the digoxin pharmacokinetics was found. However, a statistically significant
      increase in digoxin Cmax (3.03+/-0.18 nmolxl(-1) vs 2.52+/-0.19 nmolxl(-1), p <
      0.05) and Cmin (0.99+/-0.08 nmolxl(-1) vs 0.87+/-0.07 nmolxl(-1), p=0.05)
      occurred after the coadministration vs digoxin alone. It can be concluded that
      mizolastine and digoxin at therapeutic dosages can be safely coadministered.

PMID- 9629995
TI  - Pharmacokinetic overview of oral second-generation H1 antihistamines.
AB  - Specific H1 antihistamines have become the standard of treatment for relief of
      symptoms associated with seasonal allergic rhinitis. First-generation
      antihistamines are small lipophilic molecules that are associated with numerous
      adverse events largely because of their propensity to cross the blood-brain
      barrier and their cholinergic activity. Second-generation antihistamines, being
      more lipophobic, offer the advantages of a lack of CNS and cholinergic effects
      such as sedation and dry mouth, which are commonly seen in first-generation
      antihistamines. Their longer duration of action also enables a more patient
      friendly dosing regimen which increases patient compliance. This paper reviews
      the pharmacokinetic properties of these second-generation agents and is intended
      to provide comparisons that help explain differences in dosing profiles and drug
      interactions for members of this class of drugs. With the announced withdrawal of
      terfenadine from the U.S. market in early 1997, 4 second-generation
      antihistamines are currently widely available: astemizole, loratadine,
      cetirizine, and fexofenadine. Terfenadine and astemizole both produce significant
      cardiac QT interval prolongation that may progress to a rare but fatal cardiac
      ventricular tachycardia known as torsades de pointes. While only terfenadine has
      been withdrawn due to its adverse effects profile, significant warnings were
      recently issued for astemizole. The pharmacokinetic profiles of loratadine and
      cetirizine are reflective of the advantages of these agents as non-cardiotoxic
      antihistamines. With respect to the newest agent fexofenadine, the major
      metabolite of terfenadine, published reports are minimal, but its
      pharmacokinetics differs from that of terfenadine.

PMID- 9629996
TI  - Mixture in the distribution of haloperidol-induced oral dyskinesias in the rat
      supports an animal model of tardive dyskinesia.
AB  - Spontaneous adventitious oral movements which are produced in rats by very
      chronic (6-month) neuroleptic treatment have some phenomenologic and
      pharmacologic characteristics in common with tardive dyskinesia in humans.
      However, since not all of the features match, this putative model has been
      questioned and further support is warranted. Data from several laboratories
      support dichotomizing these neuroleptic-induced rat oral movements into "low" or
      "not TD-like" movements and "high" or "TD-like" movements, similar to the
      division of neuroleptic-induced involuntary movements in humans. Here, we have
      used mixture analysis to test this proposal statistically in 185 haloperidol
      treated and 127 water-treated animals. Rats from several different studies were
      grouped together to form these two cohorts. The haloperidol dose, route of
      administration, rating technique, and balanced experimental groups were held
      constant across all experiments. Results show that two distinct groups of rat
      movements are induced by very chronic haloperidol treatment (1.5 mg/kg per day).
      The "low" vacuous chewing movement (VCM) group of rats had an average of 3.6
      VCMs/5 min, and the "high" VCM group had an average of 16.1 VCMs/5 min; the
      control group, with a median VCM rate of 2.0 VCMs/5 min, demonstrated a single
      distribution. These data suggest that rats, like humans, dichotomize into two
      groups either expressing or not expressing "high" VCM dyskinesias with very
      chronic haloperidol treatment.

PMID- 9629997
TI  - Effect of serotonergic agents on adenosine A2 receptor mediated catalepsy in
      mice.
AB  - The effect of serotonergic agents was studied on the adenosine A2 receptor
      agonist NECA-induced catalepsy in mice. The 5-HT releaser fenfluramine, the 5
      HT1A agonist 8-OH-DPAT, the 5-HT(2A/1C) receptor agonist DOI and the 5-HT(2A/1C)
      receptor antagonists ketanserin and mianserin reversed NECA-induced catalepsy. p
      MPPI and ketanserin reversed the anticataleptic actions of 8-OH-DPAT and DOI,
      respectively. Further, the 5-HT reuptake inhibitor fluoxetine, the 5-HT(1B/1C)
      receptor agonist TFMPP, the 5-HT synthesis inhibitor p-CPA, the selective 5-HT1A
      receptor antagonist p-MPPI, the 5-HT(1A/1B) receptor antagonist pindolol and the
      5-HT3 receptor antagonist LY 278, 584 had no effect on NECA-induced catalepsy.
      The anticataleptic action of fenfluramine was not affected by pretreatment with p
      CPA. In p-CPA treated rats, ketanserin did not affect the anticataleptic effect
      of fenfluramine, whereas p-MPPI partially reversed this effect. It is concluded
      that modulation of serotonergic neurotransmission at 5-HT1A and 5-HT(2A/1C)
      receptors affects the cataleptic action of experimental antipsychotic agents with
      adenosine A2 receptor agonistic activity.

PMID- 9629998
TI  - CCK(B) antagonists protect against anxiety-related behaviour produced by ethanol
      withdrawal, measured using the elevated plus maze.
AB  - The effects of the CCK(B) antagonists, CAM1028 and CI988 and a CCK(A) antagonist,
      CAM1481, were studied on the anxiety-related behaviour produced by withdrawal
      from chronic ethanol treatment, using the elevated plus maze. Cessation of
      chronic ethanol administration produced a profile, in both mice and rats,
      consistent with increase in anxiety-related behaviour. In mice, SC administration
      of CAM1028 or CI988 reduced the decrease in the time spent on the open arms, the
      number of entries into these arms and the increases in the latencies to first
      open arm entry, after withdrawal from the ethanol treatment. The increases in
      stretched attend postures and head dips from the closed arms and the central
      square seen during the withdrawal phase, were also decreased by the CCK(B)
      antagonists, but the decreases in the number of rears and in general activity
      were unaffected. The doses of CAM1028 and CI988 tested were 0.1 and 1 mg/kg; for
      some of the withdrawal-induced changes in behaviour only the 1 mg/kg dose was
      effective. In contrast, the CCK(A) antagonist, CAM1481, at the same doses, had
      little effect on the anxiety-related behaviour produced by withdrawal from
      chronic ethanol treatment, although it did decrease the changes in the number of
      rears and the head dipping behaviour. In rats, the majority of the changes
      produced by withdrawal from chronic ethanol treatment were decreased by CAM1028
      at 1 mg/kg, although the decreases in open arm entries, rearing behaviour and in
      overall activity were unaffected. CAM1028, CI988 and CAM1481 had no effects on
      the behaviour of control mice or rats in the plus-maze. The results show that
      CCK(B) antagonists were effective in decreasing the majority of the anxiogenic
      effects of withdrawal from chronic ethanol treatment.

PMID- 9629999
TI  - Acquisition of oral phencyclidine (PCP) self-administration in rhesus monkeys:
      effects of dose and an alternative non-drug reinforcer.
AB  - The effects of drug dose and a non-drug alternative reinforcer on acquisition of
      oral PCP self-administration in rhesus monkeys were examined. Acquisition was
      studied using three groups of monkeys (seven subjects per group). One group
      received a low PCP dose (0.0375 mg/delivery) and the other two received a high
      PCP dose (0.15 mg/delivery). One of the high dose groups had concurrent access to
      a saccharin solution (0.03% w/v) and water during the intersession (17.5-h)
      period. Food non-restricted monkeys were initially given access to water under a
      fixed-ratio (FR) 1 schedule during daily 3-h sessions. Water was then replaced
      with PCP during the session. The monkeys were then reduced to 85% of their free
      feeding body weights and fed before the session, and the FR value was increased
      from 1 to 2, 4 and 8. Subsequently, food was given post-session and water and PCP
      were available under concurrent FR 8 schedules. At this final step of the
      procedure, acquisition of PCP self-administration was considered to occur if PCP
      intake consistently exceeded water intake. When all three groups were given
      concurrent access to PCP and water, PCP intake was greater than water intake only
      in the group of monkeys receiving the high PCP dose. PCP intake increased when
      water replaced saccharin during intersession in the high PCP dose group. Within
      group data revealed that 85.7% of monkeys acquired PCP reinforcement in the group
      given access to the high PCP dose while only 42.8% acquired in the other two
      groups. These data suggest that drug dose and presence of alternative non-drug
      reinforcers affect acquisition of drug self administration in non-human primates.

PMID- 9630000
TI  - A comparison of bd and tid dose regimens of quetiapine (Seroquel) in the
      treatment of schizophrenia.
AB  - Quetiapine (Seroquel, ICI 204,636) is an atypical antipsychotic that is effective
      in the treatment of both positive and negative symptoms of schizophrenia, and has
      a low propensity to cause extrapyramidal symptoms. The compound has a relatively
      short plasma elimination half-life (approximately 7 h). However, since dopamine
      D2 receptor occupancies correlate poorly with plasma concentrations of
      antipsychotics, plasma elimination half-life may not predict either duration of
      clinical effect or dosing frequency. Accordingly, the efficacy and tolerability
      of three dosing regimens (450 mg/day given in two or three divided doses daily,
      and 50 mg/day given twice daily) were compared in a 6-week, double-blind,
      randomized, multicentre, parallel-group study. The study recruited hospitalized
      men and women aged 18-65 years meeting DSM-IIIR criteria for acute exacerbation
      of chronic or subchronic schizophrenia. Six hundred and eighteen patients were
      randomly assigned to treatment with quetiapine 150 mg tid (n = 209), 225 mg bd (n
      = 200), or a comparator dose of 25 mg bd (n = 209). At day 42, the last day of
      randomized treatment and the primary timepoint for efficacy, quetiapine 450
      mg/day was more effective than 50 mg/day: 225 mg bd was consistently superior to
      25 mg bd in all measures of efficacy (total BPRS, P = 0.006; CGI severity, CGI
      improvement and SANS, P < 0.03), and 150 mg tid was statistically significantly
      superior to 25 mg bd with respect to BPRS total score (P = 0.05). The 225 mg bd
      and 150 mg tid groups were not significantly different from each other with
      respect to any efficacy measure. Quetiapine was generally well tolerated.
      Extrapyramidal symptom (EPS) adverse events were generally rare, and occurred
      with similar frequencies in the two 450 mg/day groups. Quetiapine was not
      associated with sustained increases in plasma prolactin at any dose. These data
      support the atypical profile developed from preclinical studies and show that
      quetiapine is an effective, well tolerated antipsychotic that can be given twice
      daily.

PMID- 9630001
TI  - A detailed characterization of the effects of four cannabinoid agonists on
      operant lever pressing.
AB  - The present experiments were conducted to investigate the effects of four
      cannabimimetics on detailed temporal parameters of operant responding. In this
      study, the behavioral output during performance of a fixed ratio 5 schedule of
      reinforcement was recorded by a computer program that measured the response
      initiation time (IT; time interval between the offset of one lever press and the
      onset of the next) and the response duration (the amount of time that elapses
      from the onset to the offset of one lever press) of each lever press. ITs were
      further partitioned into fast responses (IT=0.0-1.0 s), short pauses (IT= 1.0-2.5
      s), and long pauses (IT>2.5 s). Four cannabimimetic agents were assessed in this
      study: (R)-methanandamide (AM 356), a hydrolytically stable analog of
      arachidonylethanolamide, an endogenous ligand for the CB1 receptor; CP-55,940, a
      potent non-classical synthetic ligand; (-)-delta8-tetrahydrocannabinol (delta8
      THC), an isomer of the naturally occurring delta9-THC; and WIN 55,212-2, a
      synthetic aminoalkylindole. All four of the cannabimimetic drugs tested
      significantly suppressed operant lever pressing in a dose dependent manner. The
      rank order of potencies observed in the present study was CP-55,940>>WIN-55,212
      2>delta8-THC>AM 356, which is consistent with the rank order of affinities for
      the CB1 receptor shown by these drugs. All of the cannabimimetics substantially
      increased average IT, and also increased duration time. There was a substantial
      increase in average length of long pauses, and statistically significant but very
      small changes in the local rate of responding as measured by the average length
      of fast ITs. Cannabinoid-treated rats were largely immobile during pauses in
      responding, and these animals showed several signs of ataxia and catalepsy at the
      doses that suppressed lever pressing. Together with other data, the present
      results suggest that CB1 stimulation leads to motor effects that are associated
      with a suppression of lever pressing.

PMID- 9630002
TI  - Effects of serotonin 5-HT(2A/2C) antagonists on associative learning in the
      rabbit.
AB  - The 5-HT(2A/2C) receptor antagonist, ritanserin, was reported to retard the
      acquisition of conditioned responses (CRs) during classical conditioning of the
      rabbit's nictitating membrane (NM) response. The present study compared the
      effects of ritanserin on acquisition of CRs to a tone conditioned stimulus (CS)
      with that of the 5-HT(2A/2C) receptor antagonist, LY-53,857 and the 5-HT2A
      selective antagonist, MDL-11,939. All three drugs were injected at equimolar
      doses of 0.067, 0.67 and 6.7 micromol/kg, SC, 1 h before behavioral testing.
      Ritanserin and MDL-11,939 retarded CR acquisition to a tone CS, while LY-53,857
      had no effect. Control experiments demonstrated that ritanserin (1 micromol/kg),
      MDL-11,939 (1 micromol/kg) and LY-53,857 (2 micromol/kg) had no effect on
      baseline responding or non-associative responding to the CS. However, both
      ritanserin and MDL-11,939 impaired the performance of the unconditioned NM
      reflex, as measured by a decrease in UR amplitudes on US alone trials, while LY
      53,857 had no effect. In previously trained animals, ritanserin robustly impaired
      the performance of CRs, as measured by a reduced ability of the CS to elicit CRs,
      while the effects of LY-53,857 and MDL-11,939 were marginal. The retardation of
      associative learning produced by ritanserin and MDL-11,939 may have been due, at
      least in part, to their impairment of the NM reflex arc. Since MDL-11,939 is a
      highly selective 5-HT2A antagonist, the retardation of learning and impairment of
      UR amplitudes produced by MDL-11,939 and ritanserin may have been due to blockade
      of the 5-HT2A receptor. The ability of ritanserin and MDL-11,939 to produce
      effects on learning and performance that were opposite to that of 5-HT(2A/2C)
      agonists suggests that they may be acting as inverse agonists at that receptor.
      These results stress the importance of the serotonergic system for optimal
      associative learning and motor function.

PMID- 9630003
TI  - Studies on benzodiazepines and opioids administered alone and in combination in
      rhesus monkeys: ventilation and drug discrimination.
AB  - Benzodiazepines and opioids are co-administered recreationally as well as
      clinically; in the current study, the ventilatory-depressant and discriminative
      stimulus effects of several benzodiazepines and opioids were examined alone and
      in combination in order to evaluate any interaction between agonists from these
      pharmacological classes. The benzodiazepines alprazolam, diazepam, flunitrazepam,
      lorazepam, midazolam and triazolam and the opioids morphine and fentanyl
      decreased ventilation (V(E)) in monkeys breathing either air or 5% CO2 in air,
      although decreases in ventilation produced by opioids were greater in magnitude
      than decreases produced by benzodiazepines. Flumazenil antagonized the
      ventilatory-depressant effects of flunitrazepam and triazolam and not those of
      fentanyl; naltrexone antagonized the ventilatory-depressant effects of fentanyl
      and not those of flunitrazepam or triazolam. Interactions between the ventilatory
      depressant effects of agonists from the two classes were less than additive. In
      monkeys receiving 3.2 mg/kg per day of morphine and discriminating 0.01 mg/kg
      naltrexone, neither flunitrazepam nor triazolam substituted for naltrexone; in
      morphine-deprived monkeys, morphine, and not flunitrazepam or triazolam, reversed
      naltrexone-lever responding. Moreover, benzodiazepines did not modify the
      discriminative stimulus effects of naltrexone in morphine-treated monkeys or of
      morphine in morphine-deprived monkeys. In contrast to studies showing synergism
      between benzodiazepines and opioids, the current study suggests that, under some
      conditions, combinations of these drugs can be administered without enhancing the
      ventilatory-depressant effects of either class of drugs or the discriminative
      stimulus effects of opioids.

PMID- 9630004
TI  - N-methyl-D-aspartate receptors in the nucleus accumbens are involved in detection
      of spatial novelty in mice.
AB  - The aim of this study was to investigate the role played by intra-accumbens N
      methyl-D-aspartate (NMDA) receptors in spatial information encoding. For this
      purpose, the effect of local administration of both competitive (AP-5) and non
      competitive (MK-801) NMDA antagonists was assessed in a task designed to estimate
      the ability of rodents to encode spatial relationships between discrete stimuli.
      The task consists of placing mice in an open field containing five objects and,
      after three sessions of habituation, examining their reactivity to object
      displacement (spatial novelty) and object substitution (object novelty). The
      results show that both doses of MK-801 (0.15 and 0.3 microg/side) induced a
      selective impairment in the capability of mice to detect spatial novelty. A
      similar effect was obtained by injecting the low dose of the competitive
      antagonist AP-5 (0.1 microg/side), whereas the high dose (0.15 microg/side)
      abolished detection of both spatial and object novelty. Taken together, these
      results show that intra-accumbens injections of low doses of competitive and non
      competitive NMDA antagonists can produce selective deficits in processing spatial
      information resembling those observed after hippocampal damage. Moreover, the
      fact that pharmacological treatments spare memory processes involved in
      habituation suggests that NMDA antagonists may interfere with the formation of
      spatial representations rather than producing memory deficits per se.

PMID- 9630005
TI  - CP-154,526, a selective, non-peptide antagonist of the corticotropin-releasing
      factor1 receptor attenuates stress-induced relapse to drug seeking in cocaine-
      and heroin-trained rats.
AB  - We have found that peptide antagonists of corticotropin-releasing factor (CRF)
      receptors attenuate reinstatement of heroin and cocaine seeking induced by
      footshock. Here we examined the effect of a nonpeptide, selective CRF1 receptor
      antagonist, CP-154,526, on reinstatement of heroin and cocaine seeking induced by
      footshock. Rats were trained to self-administer heroin or cocaine (0.1 and 1.0
      mg/kg per infusion, i.v., respectively) for 9-12 days. Extinction sessions were
      given for up to 14 days, during which saline was substituted for the drugs. Tests
      for reinstatement were then conducted after exposure to intermittent footshock
      (10 or 15 min, 0.5 mA). The footshock stressor reliably reinstated extinguished
      cocaine- and heroin-taking behavior. Pretreatment with CP-154,526 (15 and 30
      mg/kg, s.c.) significantly attenuated the reinstatement effect of the stressor in
      both heroin- and cocaine-trained rats. CP-154,526, administered in the absence of
      the footshock stressor, did not affect extinguished drug seeking. In addition, in
      a separate experiment, CP-154,526 was shown not to alter high rates of lever
      pressing for a 10% sucrose solution, suggesting that the suppression of lever
      pressing in stress-induced reinstatement is not caused by a performance deficit.
      These results extend previous reports on the role of CRF in reinstatement of drug
      seeking induced by stressors. The present data also suggest that, to the extent
      that exposure to environmental stressors provoke relapse to drug use in humans,
      systemically effective CRF receptor antagonists may be of use in the treatment of
      relapse to drug use.

PMID- 9630006
TI  - Microinjection of sigma ligands into cranial nerve nuclei produces vacuous
      chewing in rats.
AB  - Many typical neuroleptics carry a high risk for producing motor side effects in
      humans, and have significant affinities for sigma (sigma) receptors. Sigma
      receptors are densely concentrated in cranial nerve nuclei that comprise the
      final common pathways for lingual, facial and masticatory movements; thus, they
      may serve as important substrates for some of the unwanted movements that can
      accompany neuroleptic treatment. Therefore, the purpose of this study was to
      evaluate whether microinjection of sigma ligands into the facial nucleus or
      spinal trigeminal nucleus, oralis would cause orofacial dyskinesias, and whether
      these effects could be attenuated with sigma receptor antagonists. Microinjection
      of the high affinity sigma ligands, di-o-tolylguanidine or haloperidol (0-10
      nmol/0.5 microl), produced a marked increase in vacuous chewing and facial
      tremors in rats, while coadministration of the functional sigma antagonists,
      BD1047 or BD1063 (5 nmol), greatly attenuated these drug-induced movements.
      Sulpiride and clozapine (10 nmol/0.5 microl), sigma inactive/dopamine active
      atypical antipsychotic drugs with a much reduced risk for producing motor side
      effects in humans, were unable to elicit orofacial dyskinesias when microinjected
      into the facial or spinal trigeminal nucleus, oralis. These studies indicate that
      sigma receptors may contribute to some forms of motor side effects resulting from
      antipsychotic drug treatment.

PMID- 9630007
TI  - Sertraline treatment does not increase plasma prolactin levels in healthy
      subjects.

PMID- 9630008
TI  - Sumatriptan lowers plasma prolactin in healthy female volunteers.

PMID- 9630009
TI  - Involvement of reactive oxygen species, protein kinase C, and tyrosine kinase in
      prostaglandin E2 production in Balb/c 3T3 mouse fibroblast cells by quinolone
      phototoxicity.
AB  - We examined the effect of an antioxidant and protein kinase inhibitors on
      prostaglandin E2 (PGE2) release from Balb/c 3T3 mouse fibroblast cells induced by
      quinolone phototoxicity. Simultaneous administration of sparfloxacin (SPFX) or
      lomefloxacin (LFLX) at 12.5 to 100 microM and ultraviolet-A (UVA) irradiation for
      10 min markedly elevated PGE2 concentration in the incubation medium, whereas
      levofloxacin (LVFX) at concentrations up to 100 microM and UVA irradiation did
      not increase PGE2 concentration. Pretreatment with 100 microM pyrrolidine
      dithiocarbamate (PDTC), an antioxidant, or 1 microM calphostin C, a selective
      inhibitor of protein kinase C (PKC), completely inhibited the elevation of PGE2
      in the 24-h incubation medium; pretreatment with 10 microM H7, a cyclic
      nucleotide-dependent protein kinase, and PKC or 1 microM herbimycin A, a tyrosine
      kinase inhibitor, inhibited the PGE2 elevation by 29 to 39%. Conversely, 25 nM
      staurosporine significantly augmented the PGE2 elevation by quinolones plus UVA.
      Interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha) were not
      detected in the incubation medium of 3T3 cells after quinolone plus UVA,
      corresponding to the lack of effect of antibodies against IL-1alpha, IL-1beta,
      and TNFalpha on PGE2 release from 3T3 cells. These results suggest that PGE2
      production in 3T3 cells by quinolone phototoxicity is modulated by reactive
      oxygen species, PKC, and tyrosine kinase, but not by IL-1 or TNFalpha.

PMID- 9630011
TI  - Oxidative DNA damage and cell proliferation in kidneys of male and female rats
      during 13-weeks exposure to potassium bromate (KBrO3).
AB  - It has been assumed that oxidative damage, including formation of 8
      hydroxydeoxyguanosine (8-OHdG) adducts in kidney DNA due to potassium bromate
      (KBrO3), a renal carcinogen to both sexes of rats, is involved in its mechanisms
      of tumor induction. However, despite the presumed existence of a repair enzyme(s)
      for 8-OHdG, there have been no reports demonstrating the changes in adduct levels
      during medium- or long-term exposure. To elucidate the actual kinetics regarding
      this parameter during the early stages of KBrO3 carcinogenesis, we measured 8
      OHdG levels in kidney DNA together with cell proliferation in renal tubules in
      both sexes of rats receiving KBrO3 at a dose of 500 ppm in the drinking water for
      1, 2, 3, 4, and 13 weeks. Rapid elevation of 8-OHdG levels was noted in treated
      male rats which persisted until the end of the experiment. Increased cell
      proliferation in the proximal convoluted tubules was also observed throughout the
      experimental period, concomitant with alpha2mu-globulin accumulation. Increase in
      8-OHdG levels in treated females first became apparent 3 weeks after the start of
      exposure, with cell proliferation only elevated at the 13-week time point. The
      present study, employing the same route and dose of KBrO3 known to cause tumors,
      strongly suggested the requirement of persistent increase of 8-OHdG for
      neoplastic conversion. Moreover, a clear sex difference in susceptibility to
      generation of oxidative stress in kidney DNA was found, in addition to alpha2mu
      globulin-dependent variation in cell proliferation in the renal tubules.

PMID- 9630010
TI  - FK506 (Tacrolimus) decreases the cytotoxicity of cyclosporin A in rat hepatocytes
      in primary culture: implication of CYP3A induction.
AB  - Tacrolimus (FK506) and cyclosporin A (CsA) are two potent immunosuppressants
      mainly metabolized by hepatic cytochrome P-450 3A (CYP3A) monooxygenase. The aim
      of this study was to compare the toxic effects of the two drugs on hepatocytes in
      primary culture as a function of their metabolism and to explore the variations
      of cytotoxicity when both drugs are associated. The cytotoxicity of FK506 and
      CsA, as expressed by their IC50 values, was of the same order but with a switch
      according to whether hepatocytes were induced or uninduced by dexamethasone, CsA
      being more toxic in its native form and FK506 through its metabolism. Similar
      results were obtained with the intracellular calcium content. When both drugs
      were associated at their IC50 values, the expected additive cytotoxic effect was
      not observed. Moreover, when small quantities of FK506 were added to CsA at its
      IC50, cell viability improved in the induced cultures. It is hypothesized that
      the interaction between the two drugs relies on a mechanism involving both
      competition of FK506 and CsA for CYP3A and of their immunophilin complexes for a
      common site on the calcineurin-calmodulin complex.

PMID- 9630012
TI  - Oxidative effects in human erythrocytes caused by some oximes and hydroxylamine.
AB  - Both oximes and hydroxylamine (HYAM) are compounds with known oxidative capacity.
      We tested in vitro whether acetaldoxime (AAO), cyclohexanone oxime (CHO), methyl
      ethyl ketoxime (MEKO) or HYAM affect haemoglobin oxidation (into HbFe3+),
      formation of thiobarbituric acid reactive substances (TBARS), and glutathione
      (GT) depletion in human haemolysate, erythrocytes or blood. All these parameters
      are known to be related to oxidative stress. Glutathione S-transferase (GST)
      activity was measured as it may be affected by oxygen radicals. All three oximes
      caused a low degree of HbFe3+ accumulation in erythrocytes. This was higher in
      haemolysates indicating that membrane transport may be limiting or that
      protective mechanisms within erythrocytes are more effective. HbFe3+ accumulation
      was lower for the oximes than for HYAM. AAO and HYAM caused TBARS formation in
      blood. For HYAM this was expected as free radicals are known to be generated
      during HbFe3+ formation. Free radical generation by AAO and HYAM in erythrocytes
      was confirmed by the inhibition of GST. For the other two oximes (CHO and MEKO)
      some special effects were found. CHO did inhibit erythrocyte GST while it did not
      cause TBARS formation. MEKO was the least potent oxime as it caused no TBARS
      formation, little HbFe3+ accumulation and little GST inhibition in erythrocytes.
      However, GT depletion was more pronounced for MEKO than for the other oximes,
      indicating that glutathione conjugation occurs. TBARS formation, GT depletion and
      GST modulation caused by the oximes and HYAM were also tested in rat hepatocytes.
      However, no effects were found in hepatocytes. This suggests that a factor
      present in erythrocytes is necessary for free radical formation. Studies with
      proposed metabolites of the oximes (i.e. cyclohexanone, acetaldehyde or
      methylethyl ketone) and addition of rat liver preparations to the erythrocyte
      incubations with oximes, suggest that metabolism is not a limiting factor in
      erythrocyte toxicity.

PMID- 9630013
TI  - Computer-based bioassay for evaluation of sensory irritation of airborne
      chemicals and its limit of detection.
AB  - We expanded a previously described rule-based computerized method to recognize
      the sensory irritating effect of airborne chemicals. Using 2-chlorobenzylchloride
      (CBC) as a sensory irritant, characteristic modifications of the normal breathing
      pattern of exposed mice were evaluated by measuring the duration of braking (TB)
      after inspiration and the resulting decrease in breathing frequency. From the
      measurement of TB, each breath was then classified as normal (N) or sensory
      irritation (S). Using increasing exposure concentrations, the classification S
      increased from < or = 2% (equivalent to sham-exposure) to 100% within a narrow
      exposure concentration range. The potency of CBC was then evaluated by
      calculating the concentration necessary to produce 50% of the breaths classified
      as S, i.e., S50. This approach is easier to use than obtaining RD50 (decrease in
      respiratory frequency by 50%) when high exposure concentrations are difficult to
      achieve. Detection limits were also established for this bioassay and experiments
      were conducted to obtain a level of response just around these limits, in order
      to delineate the practicality of using this bioassay at low exposure
      concentrations. Using this approach, sensory irritation was the only effect
      induced by CBC at low exposure concentrations. However, bronchoconstriction and
      pulmonary irritation were superimposed on this effect at higher exposure
      concentrations.

PMID- 9630014
TI  - Assessment of early acute lung injury in rodents exposed to phosgene.
AB  - Phosgene is a highly reactive oxidant gas used in the chemical industry. Phosgene
      can cause life-threatening pulmonary edema by reacting with peripheral lung
      compartment tissue components. Clinical evidence of edema is not usually apparent
      until well after the initial exposure. This study was designed to investigate
      early signs of acute lung injury in rodents within 45-60 min after the start of
      exposure. Male mice, rats, or guinea pigs were exposed to 87 mg/m3 (22 ppm)
      phosgene or filtered room air for 20 min followed by room air washout for 5 min.
      This concentration-time exposure causes a doubling of lung wet weight within 5 h.
      After exposure, animals were immediately anesthetized i.p., with pentobarbital.
      Bronchoalveolar lavage (BAL) was performed and fluid analyzed for total
      glutathione (GSH), lipid peroxidation thiobarbituric acid reactive substances
      (TBARS), and protein concentration. Lungs were perfused with saline to remove
      blood, freeze-snapped in liquid N2, analyzed for tissue GSH, and TBARS. Lung
      edema was assessed gravimetrically by measuring tissue wet/dry (W/D) weight
      ratios and tissue wet weights (TWW). W/D and TWW were significantly higher in
      mice for phosgene vs air (P=0.001, P < 0.0001, respectively), but not in rats or
      guinea pigs. Tissue TBARS was significantly higher in phosgene-exposed guinea
      pigs, P=0.027; however, BAL TBARS was higher in both rats and guinea pigs,
      P=0.013 and P=0.006, respectively. Tissue GSH was significantly lower in phosgene
      exposed rats and guinea pigs but not mice, whereas BAL GSH was higher in rats, P
      < 0.0001. There were significantly higher BAL protein levels in all phosgene
      exposed species: mice, P < 0.0001; rats, P < 0.0001; and guinea pigs, P=0.002.
      Although there appears to be a species-specific biochemical effect of phosgene
      exposure for some biochemical indices, measurement of BAL protein in all three
      species is a better indicator of ensuing edema formation.

PMID- 9630015
TI  - Quinuclidinium-imidazolium compounds: synthesis, mode of interaction with
      acetylcholinesterase and effect upon Soman intoxicated mice.
AB  - Four compounds were prepared: 3-oxo-1-methylquinuclidinium iodide (I), 2
      hydroxyiminomethyl-1,3-dimethylimidazolium iodide (II) and two conjugates of I
      and II linked by -(CH2)3- (III) and -CH2-O-CH2- (IV). The aim was to evaluate
      separately the properties of I and II as opposed to III and IV, which contain
      both moieties in the same molecule. All four compounds were reversible inhibitors
      of acetylcholinesterase (AChE; EC 3.1.1.7). The enzyme/inhibitor dissociation
      constants for the catalytic site ranged from 0.073 mM (II) to 1.6 mM (I). The
      dissociation constant of I for the allosteric (substrate inhibition) site was 4.8
      mM. Possible binding of the other compounds to the allosteric site could not be
      measured because II, III and IV reacted with the substrate acetylthiocholine
      (ATCh) and at high ATCh concentrations the non-enzymic reaction interfered with
      the enzymic hydrolysis of ATCh. The rate constants for the non-enzymic ATCh
      hydrolysis were between 23 and 37 l/mol per min. All four compounds protected
      AChE against phosphorylation by Soman and VX. The protective index (PI) of I
      (calculated from binding of I to both, catalytic and allosteric sites in AChE)
      agreed with the measured PI; this confirms that allosteric binding contributes to
      the decrease of phosphorylation rates. The PI values obtained with III and IV
      were higher than those predicted by the assumption of their binding to the AChE
      catalytic site only. The toxicity (i.p. LD50) of compounds I, II, III and IV for
      mice was 0.21, 0.68, 0.49 and 0.77 mmol/kg body wt. respectively. All four
      compounds protected mice against Soman when given (i.p.) together with atropine 1
      min after Soman (s.c.). One-quarter of the LD50 dose fully protected mice
      (survival of all animals) against 2.52 (IV), 2.00 (I and III) and 1.58 (II) LD50
      doses of Soman.

PMID- 9630016
TI  - Involvement of apoptosis in the rat germ cell degeneration induced by
      nitrobenzene.
AB  - Nitrobenezene (NB) produces germ cell degeneration, especially of spermatocytes
      in rats. To examine the possible involvement of apoptosis in this process, the
      extent and nature of nuclear DNA fragmentation after NB dosing were assessed
      using both terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling
      (TUNEL) and DNA gel electrophoresis, in addition to conventional histological and
      electron microscopic procedures. Adult Sprague Dawley rats were treated with a
      single oral dose of NB (250 mg/kg) and euthanized subsequently at 6, 12, and 24 h
      and 2, 3, 5, and 7 days. The earliest morphological signs of germ cell
      degeneration in testes were found in pachytene spermatocytes 24 h after dosing.
      Electron micrographs of degenerating spermatocytes showed marked nuclear
      chromatin condensation at the nuclear periphery and crowding of cytoplasmic
      constituents, which are characteristic of apoptosis. Coincident with the
      appearance of such morphological changes, degenerating spermatocytes contained
      fragmented DNA as revealed by TUNEL. The presence of DNA laddering, a hallmark of
      apoptosis on gel electrophoresis, was first apparent and most prominent at 24 h,
      gradually becoming less detectable. No such changes were observed up to 12 h
      after dosing or in control animals. These results demonstrated unequivocal
      involvement of apoptosis in the induction of germ cell degeneration caused by NB.

PMID- 9630017
TI  - The disposition and metabolism of 1,3,5-[U-14C]trioxane in male Wistar albino
      rats.
AB  - The present study was designed to investigate 1,3,5-[U-14C]trioxane (TOX)
      distribution, excretion and metabolism. The experiments were performed on male
      Wistar albino rats after a single administration of TOX at doses of 40 mg/kg and
      400 mg/kg. The exhaled air proved to be the main route of 14C elimination, mainly
      as 14CO2. During the first 12 h following the administration of 40 mg/kg of TOX
      the exhalation of 14CO2 was monophasic, with a half-life of 3.5 h. After the
      administration of 400 mg/kg, TOX was eliminated mainly as 14CO2 with the exhaled
      air (77%) and unchanged TOX (8%). About 3% of 14C was excreted in the urine as
      unchanged 1,3,5-trioxane. With regards to TOX elimination from blood plasma for
      the lower dose, a biphasic process was observed, with half-lives of 4.5 and 72 h.
      The amount of 14C bound by the erythrocytes was minute compared with the amount
      in blood plasma. When the higher dose of TOX was administered the efficiency of
      14C binding to the erythrocytes was found to be 10 times higher than the
      respective value for blood plasma. Among the examined tissues the highest
      concentration of TOX-derived radioactivity was detected in the liver while the
      lowest was in fat tissue and brain. A subsequent decay of radioactivity occurred
      in the tissues. The results of the present study indicate that TOX belongs to the
      group of compounds, which are rapidly eliminated from the organism; hence TOX
      should not be expected to accumulate within the tissues. The data obtained
      confirm the assumed pattern of metabolic transformation, according to which 1,3,5
      trioxane undergoes enzymatic transformation to formaldehyde, with carbon dioxide
      and water being the final products.

PMID- 9630018
TI  - N-methylcarbamoyl adducts at the N-terminal valine of globin in workers exposed
      to N,N-dimethylformamide.
AB  - N,N-dimethylformamide (DMF) is a commonly used industrial solvent. The formation
      of some metabolites of DMF in humans occurs via N-methyl-carbamoylated species
      (e.g. N-methylcarbamoylated glutathione). The aim of our study was to investigate
      whether DMF leads to N-methylcarbamoylated adducts at the N-terminal valine of
      haemoglobin (Hb). Therefore, Hb adduct levels of ten DMF exposed workers and ten
      controls were analysed by a specific and sensitive detection method using
      capillary gas chromatography and a mass selective detector (GC/MS). Using this
      method we were able to show for the first time that Hb adducts are formed during
      the metabolism of DMF in humans. The general population, however, shows still
      unidentified background levels of this adduct which are on average lower by a
      factor of 50. The pathway for the formation of the investigated DMF-Hb adduct in
      workers exposed to DMF is still unknown. As identical adducts were also found
      after exposure to methylisocyanate (MIC), our work indicates the formation of MIC
      during the metabolism of DMF. The formation of Hb adducts with DMF and its
      relevance for occupational health is a subject of further research.

PMID- 9630019
TI  - The olfactory system as a portal of entry for airborne polychlorinated biphenyls
      (PCBs) to the brain?
AB  - Ferrets, mammalian carnivores, kept in an indoor enclosure were continuously
      exposed to low concentrations of polychlorinated biphenyls (PCBs) in the ambient
      air for 5 years. After that time PCB concentrations were quantified in the
      olfactory bulbs and in the remaining brain, adipose tissue and liver. The results
      revealed unexpectedly high PCB concentrations in the olfactory bulbs, surpassing
      those in the remaining brain and the peripheral tissues. The PCB congener pattern
      in the olfactory bulbs resembled that found in the ambient air and the less
      chlorinated volatile PCBs were found in higher concentrations. We, therefore,
      assume that airborne PCBs enter directly via the olfactory system and are
      transported through the axons to the olfactory bulbs where they accumulate.

PMID- 9630020
TI  - Acute and chronic over-exertion: do depressed immune responses provide useful
      markers?
AB  - There are ethical objections to inducing cumulative muscle damage and associated
      decrements of performance deliberately in a healthy athlete. Available data on
      acute and chronic over-exertion thus include the changes of immune response
      observed following a single bout of exhausting exercise, sequential observations
      made on top-level competitors as they approach peak training periods, and
      longitudinal laboratory studies of heavy (but not necessarily damaging) bouts of
      training. In all three of these situations, subclinical muscle damage initiates
      an acute inflammatory response, with a resulting deterioration in physical
      performance. Although much smaller in degree and shorter in duration, the
      associated changes in immune function are similar to those seen in sepsis. There
      have been major advances in immunological technique over the past decade, and
      significant changes in a number of elements of the immune response can be
      identified in athletes during periods of heavy training. The most promising
      immunological marker of excessive training seems a decrease in salivary IgA
      concentration. However, no single change occurs with sufficient consistency to
      identify the individual competitor who is at risk of overtraining. Mechanisms can
      be conceived that convert a sequence of excessive training bouts into an acute
      and then a chronic inflammatory process, but the syndrome of overtraining has a
      complex overlay of biological and psychological influences. It remains more
      easily detected by decreases in physical performance and alterations in mood
      state than by changes in immune function.

PMID- 9630021
TI  - Adrenal medulla responsiveness to the sympathetic nervous activity in sprinters
      and untrained subjects during a supramaximal exercise.
AB  - The purpose of this study was to compare the adrenal medullar responsiveness to
      the sympathetic nervous activity between sprinters and untrained subjects after a
      supramaximal exercise (Wingate-test). Thirteen subjects took part in this study:
      7 male athletes (20.3+/-1.8 years) competing in sprint running (S) and 6
      untrained men (UT) (21+/-1.3 years). They performed an incremental treadmill test
      to determine the maximal oxygen uptake (VO2max), a force-velocity test and a
      Wingate-test on 3 different days, separated by a maximal interval of 15 days. The
      maximal power (Wmax) and the mean power (W) were determined from the Wingate-test
      on a cycle ergometer. Plasma lactate, adrenaline and noradrenaline concentrations
      were determined at rest (La0, A0, NA0), immediately after the Wingate-test (Amax,
      NAmax) and after 5 minutes recovery (Lamax, A5 and NA5). S exhibited higher
      performances than UT during the Wingate-test as shown by their significantly
      higher values of Wmax (1111+/-38 w in S vs 886+/-148 w in UT), W (822+/-37 w in S
      vs 646+/-69 w in UT) and Lamax (16.8+/1.8 mmol x l(-1) in S vs 12.2+/-2.5 mmol x
      l(-1) in UT). At the end of the test the NAmax values were similar in both groups
      whereas the Amax were significantly higher in S (7.6 +/- 1.4 nmol x l(-1) in S vs
      3.6 +/- 3.2 nmol x l(-1) in UT). This leads to a higher Amax/NAmax ratio for
      sprinters compared to untrained subjects (0.7+/-0.2 in S vs 0.3+/-0.2 in UT, p <
      0.05). As the disappearance of A (estimated by the Amax-A5 difference) was not
      lower in S (6.4+/1.5 nmol x l(-1) in S vs 1.8+/-4 nmol x l(-1) in UT), the higher
      Amax values in S might be explained by a greater secretion level of A. Conversely
      the identical NAmax values in both groups suggested that this kind of exercise
      induced the same sympathetic input in S and UT. Consequently the higher
      Amax/NAmax ratio in S argued in favor of a higher responsiveness of the adrenal
      medulla of sprinters to the same sympathetic input.

PMID- 9630022
TI  - Plasma testosterone and cortisol responses to training-intensity exercise in mild
      and hot environments.
AB  - Seven endurance-trained and heat-nonacclimated men (Mean+/-SEM: 20+/-1 yr; VO2max
      = 67+/-2 ml x kg(-1) x min(-1)) ran in two environments (M: 23 degrees C, H: 38
      degrees C; 7 days apart) at two absolute training-intensity velocities (S1: 240 m
      x min(-1); followed by S2: 270 m x min(-1); 10 min each) during the winter
      months. Blood samples were taken via cannula before (pre) S1 and after S1 and S2.
      Plasma testosterone (TEST) concentrations increased (p<0.05) above pre levels
      after S1 in M (19+/-3 versus 24+/-3 nmol x L(-1)) and H (18+/-2 versus 23+/-3
      nmol x L(-1)), and after S2 in H (18+/-2 versus 24+/-1 nmol x L(-1)). Plasma
      cortisol (CORT) and the molar ratio of TEST/CORT were unchanged from pre levels
      after S1 and S2 during M and H. No differences were found in plasma TEST, CORT,
      or the molar ratio of TEST/CORT between M and H. These results indicated that
      circulating levels of TEST and CORT were not changed in endurance-trained, heat
      nonacclimated athletes in response to short-duration running performed at the
      same absolute intensity in the heat, compared to mild environmental conditions.
      The lack of significant differences in the molar ratio of TEST/CORT, between the
      23 degrees C and 38 degrees C trials, suggested that this short-duration exercise
      challenge performed in the heat was no more of an anabolic or catabolic stimulus
      for these athletes.

PMID- 9630024
TI  - Anxiolytic and blood pressure effects of acute static compared to dynamic
      exercise.
AB  - This experiment tested whether state anxiety and blood pressure responses to
      exercise were influenced by the type of muscular contraction performed. On
      testing day 1, 11 volunteers completed one-repetition maximums (1-RMs) separately
      for the right and left limbs: arm extension, arm flexion, leg extension and leg
      flexion (8 total exercises). On two subsequent days, which were randomly ordered,
      subjects completed 24 minutes of either static or dynamic exercise. Both the
      static and dynamic exercise conditions involved eight 3-min exercise periods
      performed at an intensity equal to 10% of 1-RM and separated by a 1-min rest
      period. In the dynamic exercise condition, exercise was performed at a rate of 20
      contractions x min(-1). State anxiety and blood pressure were assessed
      immediately before as well as 3, 13, and 23 minutes following exercise. Heart
      rate was assessed continuously during exercise, and overall ratings of perceived
      exertion were obtained during the last 15 seconds of each 3-min exercise period.
      Two-way repeated measures ANOVAs revealed that state anxiety and systolic blood
      pressure were reduced to a similar degree following both static and dynamic
      exercise. It is concluded that anxiety and systolic blood pressure responses to
      acute exercise are not mediated by the type of muscle contraction performed.

PMID- 9630023
TI  - Dynamic knee-extensor and cycle exercise: functional MRI of muscular activity.
AB  - Repeated studies using human dynamic knee-extensor exercise have reported high
      mass specific blood flows. These studies suggest that the high perfusion-to
      muscle mass ratio can approach 400 ml(-1) x min x 100 g(-1) in the human
      quadriceps. However, in these studies mass specific blood flows were calculated
      based on the assumption that the quadriceps are the only muscles involved in the
      knee-extensor exercise, which is difficult to verify in an in vivo human model.
      Previous validations of this assumption have been performed using
      electromyography (EMG) and assessments of strain gauge tracings, but neither has
      been able to completely assess the involvement of all thigh muscles in this
      exercise. To address this issue four subjects exercised at 90% of their work rate
      maximum for 2.0-2.5 minutes (45-100 watts) and then a transverse section of the
      thigh (20 cm proximal to the knee) was studied using proton (1H) transverse
      relaxation time (T2) weighted magnetic resonance (MR) imaging to distinguish
      active from non-active muscles by the increased signal intensity (SI). On a
      separate occasion, measurements following 2.0-2.5 minutes of conventional two
      legged cycle ergometry at 90% of maximum work rate (150-400 watts) were made in
      the same subjects to contrast this traditional "whole leg" exercise with the
      unique muscle recruitment in dynamic knee-extension. Following knee-extensor
      exercise there was a clearly visible change in SI and a significant increase in
      T2 only in the four muscles of the quadriceps (P<0.05). After bicycle exercise SI
      changes and T2 revealed a varied muscle use across all muscles. From these MR
      data it can be concluded that unlike cycle exercise, in which all muscles are
      recruited to varying extents, single leg knee-extensor exercise is limited to the
      four muscles of the quadriceps. Thus, the common practice of normalizing blood
      flow and metabolic data to the quadriceps muscle mass in human knee-extensor
      exercise studies appears appropriate.

PMID- 9630025
TI  - Respiratory and metabolic responses to endurance cycle exercise in pregnant and
      postpartum women.
AB  - This study was designed to determine whether endurance cycling responses in
      pregnancy differ from those postpartum. We studied 16 women longitudinally at
      approximately 32 wk pregnancy and approximately 10 wk postpartum. We measured
      heart rate (HR), O2 uptake (VO2), CO2 output (VCO2), minute ventilation VE and
      plasma concentrations of substrates and of catecholamines at rest, during maximal
      testing, and during approximately 35-40 min of cycling at approximately 70-75%
      VO2peak. Endurance exercise time and power were 37.6+/-1.0 min and 124+/-8 W in
      pregnancy, similar to values observed postpartum. HR and respiratory responses
      near the end of endurance exercise were also unaffected by gestation, with
      pregnancy values of 173+/-3 bpm, 1.87+/-0.07 L/min VO2, and 1.68+/-0.07 L/min
      VCO2, except that VE at 70.0+/-3.5 L/min was 14% higher than postpartum; plasma
      concentrations of free fatty acids (404+/-62 micromol/L), glucose (3.34+/-0.17
      mmol/L), and lactic acid (4.51+/-0.50 mmol/L) were lower than postpartum by 9,
      24, and 19%, respectively; catecholamine concentrations were not different from
      those determined postpartum. We conclude that pregnant women are equally capable
      as are postpartum women to perform approximately 40 min of cycling at 70-75%
      VO2peak, and that the physiologic responses to endurance exercise are largely
      independent of gestation.

PMID- 9630027
TI  - Symmetry and performance in middle distance runners.
AB  - Deviations from perfect symmetry in paired traits such as ear size and nostril
      width may indicate developmental instability and/or short-term fluctuations in
      hormones. In both cases symmetry is thought to be optimal and to indicate high
      phenotypic quality. The purpose of this work was to determine the relationship
      between symmetry and performance in middle-distance runners. Fifty male subjects
      participated in this study. Deviations from perfect bilateral symmetry were
      measured in seven traits; ear size, nostril width, 2nd to 5th digit length and
      wrist width. After measurements were made the subjects were ranked for athletic
      ability and they reported their best 800 metre and 1500 metre times. Symmetric
      subjects had higher rankings for athletic ability (nostrils, p<0.001 and ears, p<
      0.001), lower best 800 metre times (nostrils, p<0.05 and ears, p<0.01) and lower
      best 1500 metre times (3rd digit, p<0.01 and ears, p<0.05) than asymmetric
      subjects. This conclusion remained essentially the same after Bonferroni
      adjustment for multiple tests and when experience and age were controlled for in
      multiple regression tests. We conclude that symmetry in traits such as nostrils
      and ears indicates good running ability. It may therefore be useful in predicting
      the future potential of young athletes.

PMID- 9630026
TI  - Evaluation of the Accusport Lactate Analyser.
AB  - An investigation of the Accusport Lactate Analyser (ACC) was undertaken to assess
      its accuracy, linearity, reliability, and versatility. Accuracy was determined by
      comparing 32 blood assays on the ACC with those obtained using the Kodak Ektachem
      E250 (E250). Linearity was determined over the range 1.2-18.7 mmol/L. Reliability
      was measured at 1.7 (low) and 14.4 (high) mmol/L concentrations. Versatility
      involved determining the optimal sample volume, influence of haematocrit, and the
      effect of time delay from sampling to assay. Assays determined using the ACC
      confirm good agreement with the E250. The difference between the two methods
      compared for lactate determination does not exceed 1.1 mmol/L for concentrations
      up to approximately 20 mmol/L. Linearity is demonstrated by the regression
      equation y = 0.026 + 0.970x, r = 0.995. Reliability is expressed by the
      coefficient of variation of 7% (low) and 4.6% (high). The optimal sample size for
      accurate assay was determined to be between 20 microL and 50 microL. Mean lactate
      value did not vary significantly between a haematocrit of 35% and 45%. The
      Accusport is accurate, linear up to at least 18.7 mmol/L, has good reliability at
      high and low concentrations, and is able to analyse whole blood up to 15 minutes
      after sample application to the reagent strip.

PMID- 9630028
TI  - The relationship of strength and muscle balance to shoulder pain and impingement
      syndrome in elite quadriplegic wheelchair rugby players.
AB  - Wheelchair athletes are susceptible to injuries related to overuse of the
      shoulder, in particular shoulder impingement syndrome. The present study examined
      the relationship of shoulder pain to demographic details, isokinetic strength and
      muscle balance in 8 elite quadriplegic rugby players. Demographic data were
      collected using personal interviews and each subject was clinically examined for
      signs of impingement syndrome by a physician. In addition each subject underwent
      bilateral isokinetic strength testing of the shoulder at 60 and 180 deg/s for
      abduction/adduction and internal/external rotation. A series of step-wise
      multiple discriminant analysis successfully predicted clinical symptoms from
      demographic, muscular strength and balance data. In particular, there was a
      significant deficit in adductor strength and this was related to shoulder pain
      and wasting of the scapular muscles. This strength deficit may be due to the high
      level of spinal lesions in the quadriplegic population. The level of spinal
      lesion may contribute to the aetiology of shoulder pathology in quadriplegia, and
      differentiate it from that observed in able-bodied athletes who exhibit weak
      abductors.

PMID- 9630029
TI  - Sickle cell trait in Ivory Coast athletic throw and jump champions, 1956-1995.
AB  - In order to assess the performance of subjects with sickle cell trait (SCT)
      during brief and explosive exercise involving mainly alactic anaerobic
      metabolism, the percentage of athletes with SCT was determined in Ivory Coast
      track and field throw and jump champions, both men and women, for the period 1956
      1995. Thirty-four (27.8%) sickle cell trait carriers (SCTC) were identified among
      the 122 national champions that we were able to contact. These 34 SCTC had won 78
      national titles (24.5%) and established 37 national records (43.5%), distributed
      among the throw and jump events. These percentages were significantly higher than
      the prevalence of SCT in the general Ivory Coast population (12.0%). The women's
      high jump and men's shot put events had the highest percentages of SCTC record
      holders (90.9% and 87.5%, respectively). Moreover, the two top national record
      holders and title winners, one man and one woman, were SCTC athletes, and their
      hemoglobin S percentage (HbS: 39.1% and 39.4%, respectively) and mean corpuscular
      volume (MCV) excluded an associated alpha-thalassemia. We conclude that the
      significantly higher percentage of SCTCs among Ivory Coast track and field
      champions, as compared to the percentage in the general population suggests that
      SCT may be a determinant factor for success in brief and explosive track and
      field events involving mainly alactic anaerobic metabolism.

PMID- 9630031
TI  - The problems to study plasma lactate.

PMID- 9630030
TI  - Cough induced stress fracture and arthropathy of the ribs at extreme altitude.
AB  - Cough and chest wall pain at high altitude have only received passing mention in
      the medical literature. Increased minute ventilation of cold dry air at very high
      altitude is likely to cause airway irritation. This in turn may result in airway
      drying, mucus production, postnasal drip from vasomotor rhinitis, and
      bronchospasm acting individually or in combination to stimulate the vagal cough
      reflex. The cough is exacerbated further at extreme altitudes above 5500 m, and
      may result in intercostal muscle strain and single or multiple rib fractures. We
      present a case of multiple cough induced stress fractures and arthropathy
      documented by technetium-99 bone scan in a high altitude climber and suggest the
      addition of the term High Altitude Cough Syndrome (HACS) to the medical syntax to
      identify this discrete medical problem of exposure to very high altitude.

PMID- 9630032
TI  - Diffuse renal cystic disease in children: morphologic and genetic correlations.
AB  - During a 5-year period, we evaluated seven infants and two fetuses who presented
      with enlarged, hyperechoic kidneys. In each, the initial clinical diagnosis was
      autosomal recessive polycystic kidney disease (ARPKD). Among the seven unrelated
      infants were three Caucasian and four African-American infants. No syndromic
      stigmata were evident in any of these infants. At the time of the initial
      evaluation, the family data were incomplete for four infants. The two fetuses
      were presumed to be at-risk for ARPKD based on the diagnosis in previous
      siblings. Renal histopathology was evaluated in all nine cases and revealed a
      spectrum of cystic disease ranging from ARPKD to glomerulocystic kidney disease
      to autosomal dominant polycystic kidney disease to diffuse cystic dysplasia. In
      the eight cases for whom liver histopathology was available, varying degrees of
      biliary dysgenesis were evident. We present a detailed analysis of the key
      histopathological features in each case and discuss the histopathological
      findings in an embryological context. In addition, we address the current role of
      molecular genetics in the diagnostic evaluation.

PMID- 9630033
TI  - Pseudoxanthoma elasticum: a rare cause of hypertension in children.
AB  - We describe an 11-year-old girl with severe renin-dependent hypertension. She had
      characteristic cutaneous, ocular, and vascular signs of pseudoxanthoma elasticum
      (PXE), and the diagnosis was confirmed histologically. Because PXE is a
      heterogeneous heritable disorder, the family was evaluated for this condition.
      Since the patient's mother and brother showed some manifestations of PXE,
      autosomal dominant inheritance is the most likely inheritance pattern in this
      family.

PMID- 9630034
TI  - Neonatal Bartter syndrome: spontaneous resolution of all signs and symptoms.
AB  - This baby boy was born after a pregnancy complicated by severe polyhydramnios at
      a gestational age of 28 weeks. Analysis of the amniotic fluid had shown a high
      chloride content, but normal concentrations of sodium, potassium, and calcium.
      After birth he displayed extreme polyuria, severe renal sodium and chloride loss,
      and marked hypercalciuria. Five weeks after birth, his sodium chloride loss
      turned into renal potassium loss, along with a marked decrease in urine output.
      All these features are characteristic of the neonatal variant of Bartter
      syndrome. He was discharged after 11 weeks with oral supplements of sodium
      chloride, potassium gluconate, and 500 ml of fluid. The follow-up for a period of
      6 years showed a surprising evolution: he has no hypokalemic alkalosis, no
      polyuria, and no hypercalciuria; growth and development are within the normal
      ranges and, at the time of writing, he is a healthy boy needing no medication and
      with no medical problems whatsoever.

PMID- 9630035
TI  - A model of sterile vesicoureteric reflux in the sheep.
AB  - Eighteen Coopworth ewe lambs were divided into three groups based on the initial
      cystourethrogram and cystometry findings at 5-7 weeks of age: group 1, 6 lambs
      with spontaneous low-pressure bilateral vesicoureteric reflux (VUR) on bladder
      filling were used to study the natural history of reflux; group 2, 5 lambs with
      no VUR detected were used to establish an experimental model of bilateral VUR
      using an unroofing surgical procedure; group 3, 7 lambs with spontaneous VUR
      detected during micturition had the same surgical procedure to increase the
      degree of VUR. All three animal groups were followed for 4-10 months. Spontaneous
      VUR was demonstrated in 13 of 18 lambs (25/36 ureters). The presence and severity
      of spontaneously occurring reflux in group 1 lambs diminished with increasing
      age. VUR was created successfully in group 2 and increased in degree in group 3
      animals. The only significant histological finding in all three animal groups
      with grades II and III VUR was distal renal tubular dilatation. The sheep is a
      useful and readily available animal for studying VUR. During 4-10 months of
      follow-up, sterile reflux without bladder outflow obstruction resulted in distal
      renal tubular dilatation, but no renal parenchymal damage.

PMID- 9630036
TI  - The interaction of glomerular mesangial cells and epithelial cells.
AB  - The interaction of cells within the glomerulus plays an important role in the
      development and progression of glomerular disease. To investigate the interaction
      of glomerular mesangial cells (GMC) and epithelial cells (GEC), and mediator(s)
      of this interaction, we investigated the effect of Adriamycin (doxorubicin
      hydrochloride)-induced (ADR) rat GMC-conditioned medium (GMC-CM) on the
      incorporation of 35S, 3H-leucine, and 3H-thymidine in normal rat GEC, as well as
      3H-thymidine uptake by normal rat GMC in response to ADR-rat GEC-CM. In addition,
      changes in the responsiveness to interleukin-6 (IL-6) and the products of IL-6
      were assessed in ADR-rat GMC. The results showed that: (1) GMC-CM of ADR-rat with
      heavy proteinuria stimulated GEC proliferation and the synthesis of sulfated
      compounds and protein, while the GEC-CM of ADR-rat from the same nephrotic period
      increased GMC proliferation; (2) the ADR-rat GMC had altered responsiveness to IL
      6 and its products. The stimulation index results demonstrated the interaction of
      GMC and GEC in the ADR-induced rat model, and that this interaction related
      closely to the degree of proteinuria and was mediated by soluble products of the
      damaged glomerular cell.

PMID- 9630037
TI  - Rat models of normocalcemic hypercalciuria of different pathogenic mechanisms.
AB  - Hypercalciuria was induced in female Sprague-Dawley rats, aged 40+/-2 days, by 7
      day administration (mean+/-SEM) of calcitriol (5.4+/-0.1 ng/100 g per day,
      intraperitoneal), furosemide (14.9+/-1.9 mg/100 g per day, oral), or ammonium
      chloride (3.8+/-0.1 mEq/100 g per day, oral). Calciuria increased from 1.9+/-0.2,
      1.6+/-0.2, and 1.9+/-0.3 to 5.4+/-0.5, 4.0+/-0.9, and 5.4+/-0.5 mg/100 g per day
      in the calcitriol (VD, n = 9), furosemide (F, n = 6), and ammonium chloride (AC,
      n = 10) groups, respectively. Calciuria did not change (1.9+/-0.3 vs. 1.6+/-0.1
      mg/100 g per day) in control rats (n = 8). Ninety-six percent of treated rats
      became hypercalciuric as assessed by urine calcium excretion above the 90th
      percentile of normal values. Hypercalciuria was of similar degree in the three
      groups of rats and was not associated with hypercalcemia, metabolic acidosis,
      severe serum electrolyte imbalance, or growth impairment. VD rats had low serum
      parathyroid hormone (PTH) concentrations (3.0+/-0.5 pg/ml vs. 15.8+/-1.3 pg/ml in
      controls, P <0.05), whereas serum PTH was not significantly elevated in F rats
      (16.2+/-1.8 pg/ml). Thus, the protocol caused three forms of hypercalciuria that
      mimicked the clinical conditions of idiopathic hypercalciuria in humans and may
      clearly be differentiated according to their mechanism of production. This
      experimental model of normocalcemic hypercalciuria may be useful to clarify
      unknown aspects of pathogenesis and pathophysiology of idiopathic hypercalciuria
      in children.

PMID- 9630038
TI  - Asymptomatic vesicoureteral reflux detected by neonatal ultrasonographic
      screening.
AB  - Renal ultrasonography was performed in 2,384 healthy and asymptomatic neonates.
      The definition and grading of hydronephrosis was according to the system of the
      Society for Fetal Urology. Voiding cystourethrography was performed in the cases
      with moderate to severe hydronephrosis or persistent mild hydronephrosis. In
      cases with vesicoureteral reflux (VUR), a dimercaptosuccinic acid (DMSA) renal
      scan was arranged immediately to evaluate the renal parenchyma. VUR was diagnosed
      in 30 infants with a prevalence of 1.26%; 7 had bilateral VUR. The male/female
      ratio was 4:1 and the right/left ratio was 1.85:1. Comparing with the abnormal
      ultrasonographic findings, VUR appeared ipsilaterally in 23 ureters and
      contralaterally in 14 ureters. Using ultrasonography for diagnosing VUR, the
      sensitivity, specificity, positive predictive value, and negative predictive
      value were 62.2%, 36.1%, 11.0%, and 88.2%, respectively. DMSA renal scan was
      performed in 31 refluxing kidneys, and congenital renal scarring was found in 9
      (29.0%) kidneys. Six neonates underwent reimplantation surgery. We conclude that
      although ultrasonography is not a reliable tool for diagnosing VUR, it can detect
      many cases of VUR during the newborn stage using our screening program, which
      thus makes early treatment from the neonatal period possible. Whether our
      screening program can improve the outcome of VUR will require further follow-up.

PMID- 9630039
TI  - Urinary tract infections per se do not cause end-stage kidney disease.
AB  - The objective of this study was to determine the frequency with which urinary
      tract infection (UTI) in the absence of concomitant underlying abnormalities
      caused end-stage renal disease (ESRD). The records of 102 patients with ESRD
      (disease necessitating dialysis and/or transplant) seen at Children's Mercy
      Hospital during a 10-year period (1986- 1995) were reviewed. Obstructive
      uropathy, aplastic/hypoplastic/dysplastic kidneys, polycystic kidney disease,
      congenital nephrotic syndrome, acquired glomerulonephritis, idiopathic
      interstitial nephritis, hemolytic uremic syndrome, and a variety of systemic
      conditions were the cause of ESRD in 99 children; 3 children had reflux
      nephropathy, 1 of whom had no history of a UTI and another who had a single,
      afebrile UTI. A girl with a history of recurrent UTIs since 4 years of age had an
      elevated serum creatinine and grade II-III bilateral vesicoureteric reflux when
      evaluated at 8 years of age. She had ureteral reimplantations and control of the
      infections, but progressed to ESRD. This child appears to be the only 1 of 102
      children who developed ESRD because of acquired renal injury in which UTIs were
      an important contributing factor.

PMID- 9630040
TI  - Calyceal microlithiasis in children: report on 196 cases.
AB  - Recognition of children at greatest risk for urolithiasis may allow early
      detection or prevention of stone formation. We report clinical data from 196
      children aged 0.9-15.9 years in whom renal ultrasound examination revealed
      hyperechogenic spots in renal calyces less than 3 mm in diameter. We called this
      finding "calyceal microlithiasis" (CM). There was a history of urolithiasis in
      70.4% of patients in at least one first- or second-degree relative. Presenting
      symptoms were recurrent abdominal pain, dysuria, and hematuria, occurring alone
      or in combination. Hematuria was the presenting symptom in 41% of patients and
      was the only urinary finding in more than one-third. Hypercalciuria was present
      in about one-third and hyperuricuria in one-fifth of the patients. Of 29 patients
      who were followed for at least 2 years, 9 developed calculi 4-7 mm in diameter.
      CM possibly represents the first step in calculus formation. The finding of CM
      might explain a number of symptoms and signs that are often mild and non
      specific, thus reducing invasive diagnostic procedures.

PMID- 9630041
TI  - Aminoaciduria and glycosuria following severe childhood lead poisoning.
AB  - To determine the incidence of renal functional abnormalities after lead
      poisoning, we evaluated the parameters of renal tubular function in 134 children
      and young adults, 8-13 years after chelation therapy for severe lead poisoning.
      There was no evidence of hypertension or reduced kidney function as assessed by
      serum creatinine (Cr) concentrations. Urinary alpha-amino nitrogen (Uaan)
      concentrations were significantly increased compared with 19 healthy age-matched
      controls. Ninety-four children (70%) had aminoaciduria (Uaan/Cr >0.23). Urinary
      glucose excretion was also significantly higher than that of 2 historical
      controls. Thirty-two children (24%) had glycosuria (>125 mg/24 h). Fractional
      excretion of phosphate was normal in all children. We conclude that a partial
      Fanconi syndrome can persist up to 13 years after childhood lead poisoning.

PMID- 9630043
TI  - Low levels of serum erythropoietin in children with endemic hemolytic uremic
      syndrome.
AB  - Serum erythropoietin (EPO) levels were measured in ten previously non-transfused
      children with hemolytic uremic syndrome (HUS). Complete blood cell count, serum
      EPO, and renal function tests were carried out upon admission and weekly
      thereafter. Blood samples were obtained: (1) prior to the first transfusion; (2)
      after the first transfusion but before recovery from renal failure; (3) during
      the recovery stage. All patients required transfusions (mean 1.8+/-0.8 per
      child). Absolute values of EPO correlated positively with the hematocrit during
      the three stages (r = 0.53, 0.36, and 0.12, respectively) which is opposite to
      expected results. The observed EPO logarithm/predicted EPO logarithm upon
      admission was low (0.70+/-0.08), falling further during stage 2 (0.57+/-0.03),
      but increasing thereafter (0.78+/-0.07) without reaching normal values. The
      reticulocyte production rate followed a parallel course (0.74+/-0.14, 0.54+/
      0.11, and 0.60+/-0.10, respectively). On comparing the observed serum EPO levels
      with those expected, 9 of 11 pre-transfusion samples showed low values; in stage
      2, all samples were below normal; in the recovery phase most (77.8%) were still
      low. Our results show an inadequate EPO synthesis in children with HUS, which
      could play an important pathogenic role, since it aggravates the severity of the
      existing hemolytic anemia; the secondary inhibitory effect of repeated
      transfusions exacerbates this inadequate synthesis.

PMID- 9630042
TI  - Cholelithiasis following Escherichia coli O157:H7-associated hemolytic uremic
      syndrome.
AB  - Sequelae of Escherichia coli O157:H7-associated hemolytic uremic syndrome (HUS) 2
      3 years following an outbreak in Washington State have been prospectively studied
      to identify predictors of adverse sequelae. Logistic regression analysis was used
      to examine associations between findings in the acute course and long-term renal
      and gastrointestinal outcomes. Twenty-one percent of patients had
      gastrointestinal sequelae, which included cholelithiasis resulting in
      cholecystectomy (3/29), persistent pancreatitis (2/29), late colon stricture
      (1/29), and/or glucose intolerance (1/29). Logistic regression analysis found
      long-term gastrointestinal sequelae were higher in patients who, during HUS, had
      hypertension [odds ratio (OR) = 21.2, 95% confidence interval (CI) = 1.9-164.4, P
      = 0.01] or gastrointestinal complications (OR = 21.2, 95% CI = 1.9-164.4, P =
      0.01). Renal sequelae were seen in 35% of patients. One patient (4%) had
      persistent hypertension and 9 (31%) had minor urinary findings (hematuria or
      proteinuria). Thrombocytopenia lasting longer than 10 days during the acute
      illness was associated with a risk for subsequent renal sequelae (OR = 15.0, 95%
      CI = 1.98-1,703.0, P = 0.009). We conclude a high incidence of gastrointestinal
      sequelae, especially cholelithiasis presenting long after the acute illness, may
      be seen with HUS. The short follow-up period may underestimate the extent and
      severity of eventual renal sequelae.

PMID- 9630044
TI  - Hemolytic uremic syndrome and thymic dysplasia in an infant.
AB  - A 33-day-old male infant was admitted to the neonatal intensive care nursery
      because of respiratory distress, grunting, cyanosis, and radiological findings of
      bilateral bronchopneumonia. He responded well to intensive therapy, but 11 days
      later developed hemolytic uremic syndrome, which was treated conservatively with
      prednisone and plasma transfusions with good response. The hemolytic uremic
      syndrome resolved, but he subsequently developed severe recurrent infections of
      unknown etiology and died at the age of 78 days. Necropsy findings revealed
      necrotizing enterocolitis as well as dysplasia of the thymus and other lymphoid
      tissues, compatible with the diagnosis of immunodeficiency disorder.

PMID- 9630045
TI  - HLA-DQB1 and DRB1 alleles in Egyptian children with steroid-sensitive nephrotic
      syndrome.
AB  - Steroid-sensitive nephrotic syndrome (SSNS) of children has been associated with
      several HLA-DR and DQ alleles. To investigate this association in Egyptian
      children, 27 patients with SSNS were typed for HLA-DRB1 and DQB1 alleles using
      DNA polymerase chain-reverse hybridization technique. The results were compared
      with 121 healthy subjects for HLA-DRB1 and 59 subjects for DQB1 alleles. We found
      that: (1) patients have higher frequencies of both DQB1 *0601 (81.5% vs. 10.2% in
      controls, Pc=0.0001) and DRB1 *01 (44.4% vs. 3.3% in controls, Pc=0.00003). Their
      relative risks are significantly high [38.9, confidence interval (CI)=10.7-140.7,
      and 23.4, CI=6.7-81.9, respectively]; (2) the frequency of DRB1 *11 alleles was
      low in SSNS patients (3.75% vs. 32.2% in controls), but was not significant when
      P was corrected (P=0.005, Pc=NS). These findings suggest that DQB1 *0601 and DRBI
      *01 or closely associated unknown genes confer susceptibility to SSNS. However,
      further studies with larger numbers of patients are needed.

PMID- 9630046
TI  - Methylprednisolone pulse therapy in the treatment of severe forms of Schonlein
      Henoch purpura nephritis.
AB  - Between 1980 and 1994, 38 children with severe forms of Schonlein-Henoch purpura
      glomerulonephritis were entered into a prospective study to evaluate
      methylprednisolone pulse therapy on the outcome of nephropathy in terms of
      clinical symptoms and histopathological changes. The patients were considered at
      risk of developing chronic renal failure when they presented with a nephrotic
      syndrome and/or had 50% or more crescentic glomeruli. Initial renal biopsies were
      obtained from all patients and revealed diffuse proliferative endocapillary
      glomerulonephritis in 2, focal and segmental glomerulonephritis in 4, and endo-
      and extracapillary glomerulonephritis in 32, 21 of whom had 50% or more glomeruli
      with crescents. Patients were treated with intravenous pulse methylprednisolone
      (3 days) followed by oral prednisone (3.5 months). At the latest follow-up, 1-16
      years after initiation of therapy, 27 children had clinically recovered, 3 showed
      minimal urinary abnormalities, 4 persistent nephropathy, and 4 had progressed to
      end-stage renal failure. Sequential renal biopsies were obtained from 30
      patients, 7-25 months after initiation of therapy. The clinical outcome
      correlated well with of the activity (hypercellularity, cellular and
      fibrocellular crescents, and interstitial edema with mononuclear cell
      infiltrates) and the chronicity (fibrous crescents, glomerular sclerosis, tubular
      atrophy, and interstitial fibrosis) indexes of post-therapy biopsies. Of
      particular interest were the post-therapy biopsies of the 18 patients who
      clinically recovered. They showed a significant decrease of the activity index
      from 5.1+/-1.1 to 0.4+/-0.8 with a decrease or even a disappearance of IgA
      deposits, while the chronicity index remained low (0.4+/-0.8 compared with 1.4+/
      1). Although uncontrolled, our study suggests that methylprednisolone pulse
      therapy is effective in those patients at risk of progression of their
      nephropathy, especially if started early during the course of the disease before
      the crescents become fibrous.

PMID- 9630047
TI  - Multiple combined therapy for severe Henoch-Schonlein nephritis in children.
AB  - From 1980 through 1992, 14 children with Henoch-Schonlein nephritis (HSN) showing
      severe glomerular changes (grade IV or V) were given a multiple combined therapy
      with prednisolone, cyclophosphamide, heparin/warfarin, and dipyridamole, and were
      followed for 7.5+/-0.9 years. The period between the onset of nephritis and the
      start of therapy was 0.8+/-0.4 years. Ten patients underwent follow-up biopsy
      after therapy. The percentage of glomeruli having crescents/segmental lesions was
      significantly reduced after therapy (70%+/-5% vs. 42%+/-7%, P <0.01), due mainly
      to the resolution of crescents (51%+/-8% vs. 13%+/-5%, P <0.01). Thus,
      histological grade was significantly improved (5 grade IV and 5 grade V vs. 7
      grade III and 3 grade IV, P <0.01). After an average follow-up period of 7.5
      years, 9 patients showed normal urine and renal function, 4 showed minor urinary
      abnormalities, and 1 heavy proteinuria. No patient developed chronic renal
      insufficiency. These findings suggest that the multiple combined therapy could be
      effective. for histologically severe HSN, although a prospective controlled study
      should be performed.

PMID- 9630048
TI  - Primary vesicoureteral reflux: review of current concepts.
AB  - The well-known association between vesicoureteral reflux and urinary tract
      infection is the basis for pathophysiological and therapeutic implications which
      have dominated the literature on the subject for the last 2 decades. We
      critically review the following issues: (1) does urinary tract infection cause
      reflux? (2) does reflux predispose to infection? (3) does reflux predispose to
      pyelonephritis? (4) does reflux predispose to a renal parenchymal scar? (5) does
      long-term urinary antibiotic prophylaxis prevent renal damage in patients with
      reflux? We conclude that none of the reviewed issues have been rigorously proven
      or validated and that the role of vesicoureteral reflux in urinary tract
      infections needs to be redefined through well-designed, multicenter, prospective,
      randomized, controlled studies using state of the art renal imaging techniques.

PMID- 9630049
TI  - Clinical quiz. Trichomoniasis.

PMID- 9630050
TI  - A moratorium should be placed on the use of short-acting nifedipine for
      hypertensive crises.

PMID- 9630051
TI  - Conversion from Sandimmun to Neoral in stable pediatric renal transplant
      recipients.

PMID- 9630052
TI  - Renal tubular acidosis and osteopetrosis with carbonic anhydrase II deficiency.

PMID- 9630053
TI  - The growth pattern of transplanted children. Should I start this boy on growth
      hormone or can I wait?

PMID- 9630054
TI  - Bridging the generation gap.

PMID- 9630055
TI  - Health and productivity of older workers.
AB  - The purpose of this paper is to present a summary of a critical review of the
      literature on age, health, and work. The health of older workers is a concern to
      the extent that the productivity of older workers is considered to be a function
      of age-related health, the general conclusion being that age-related declines in
      health inevitably lead to decreased productivity. This paper investigates the
      implications of age-related physiological and psychological changes on the
      productivity of older workers, by focusing on a critical examination of the ways
      in which productivity has been conceptualized and operationalized. This paper
      concludes that the emerging concept of "work capacity" has the greatest potential
      for addressing the productivity issues of workforce aging. Implications for
      public and corporate policy and for further research are also examined.

PMID- 9630056
TI  - Ectopic pregnancy and occupational exposure of hospital personnel.
AB  - OBJECTIVES: An earlier study found a relationship between occupational exposure
      to antineoplastic drugs and ectopic pregnancy. The present investigation aimed at
      confirming this finding in a larger and specifically planned study and at
      analyzing the relationship between ectopic pregnancy and other chemical or
      physical agents in the hospital work environment. METHODS: A case-referent study
      (140 cases and 279 referents) was carried out in 1995 in a population of women
      working in hospitals throughout France. The sample size was computed to have an
      80% statistical power to detect a 2-fold increased risk of ectopic pregnancy
      (odds ratio 2). Information was collected about past and present work conditions
      (exposures to antineoplastic drugs, solvents, disinfectants, anesthetic gases and
      ionizing radiation), and known risk factors of ectopic pregnancy. Multivariate
      analysis was performed using logistic regression. RESULTS: No significant
      association between occupational exposure and ectopic pregnancy was found, either
      when past exposure was considered or when exposure was considered within the 3
      months before conception. The relationships remained nonsignificant after
      adjustment for job category and for the known risk factors of ectopic pregnancy.
      CONCLUSIONS: It was concluded that the results of this study should be
      interpreted as an absence of relationship between exposure to chemical or
      physical agents and ectopic pregnancy.

PMID- 9630057
TI  - Prevalence of antibodies specific to Puumala virus among farmers in Sweden.
AB  - OBJECTIVES: The Puumala virus is the causative agent of nephropathia epidemica, a
      European form of hemorrhagic fever with a renal syndrome. From its reservoir in
      bank voles, the virus is spread by airborne transmission to humans. Occupational
      risks for the acquisition of nephropathia epidemica are not well defined. The
      prevalence of serum antibodies to Puumala virus was determined for Swedish
      farmers. From a comparison of the prevalence among farmers from various parts of
      the country, the assumption that Puumala virus occurs endemically only in the
      northern and central parts of Sweden was also tested. METHODS: Serum samples from
      910 farmers and 663 referents living in various rural parts of Sweden were tested
      with an enzyme-linked immunosorbent assay, using a recombinant nucleocapsid
      protein of Puumala virus as the antigen. RESULTS: North of a latitude of 59
      degrees N, the prevalence of Puumala virus antibodies was significantly higher
      among farmers (12.9%) than among referents (6.8%). In the southern areas,
      antibodies to Puumala virus were rare, and altogether only 2 of 459 persons had
      antibodies. Seropositive persons did not differ from seronegative ones with
      regard to blood pressure, and they did not comprise cases of chronic renal
      disease. CONCLUSIONS: Serological evidence confirmed that the exposure of humans
      to Puumala virus is firmly restricted to the northern and central parts of
      Sweden. In addition the evidence indicated that, in this region, farming is
      associated with an increased risk of contracting hantavirus infection.

PMID- 9630058
TI  - Radiographic abnormalities among Finnish construction, shipyard and asbestos
      industry workers.
AB  - OBJECTIVES: The prevalence of asbestos-related radiographic abnormalities was
      surveyed among Finnish construction, shipyard, and asbestos industry workers.
      METHODS: The radiographic screening focused on active and retired workers who
      were under the age of 70 years and had been employed for at least 10 years in
      construction or for at least 1 year in shipyards or in the asbestos industry. In
      1990-1992, 18,943 people participated in an X-ray examination of the lungs and an
      interview on work history and exposure. The criteria for a positive radiological
      finding were (i) small irregular lung opacities clearly consistent with
      interstitial pulmonary fibrosis (ILO 1/1 or higher), (ii) lung opacities
      indicating mild pulmonary fibrosis (ILO 1/0) with unilateral or bilateral pleural
      plaques, (iii) marked adhesions with or without thickening of the visceral
      pleura, or (iv) findings consistent with bilateral pleural plaques. RESULTS:
      Fulfilling the criteria were 4133 workers (22%) (22% from construction, 16% from
      shipyards, and 24% from the asbestos industry). The radiological findings
      included signs of pulmonary fibrosis (3%), changes in the visceral pleura (7%),
      bilateral plaques (17%), and unilateral plaques (10%). Occupational disease was
      diagnosed according to the Finnish insurance regulations for three-fourths of
      those referred for further examinations, 96% being abnormalities in the pleura
      and 4% being asbestosis. CONCLUSIONS: Exposure to asbestos dust has been common
      in ordinary construction work, and, consequently, radiographic abnormalities
      (mostly pleural) occur frequently among active and retired construction workers.

PMID- 9630059
TI  - Occupational risk factors of lung cancer in Sao Paulo, Brazil.
AB  - OBJECTIVES: This study estimated the risk of occupational exposure for lung
      cancer in the metropolitan region of Sao Paulo, the largest urbanized and
      industrialized area in Brazil. METHODS: In this hospital-based case-referent
      study of 398 cases and 860 referents, the cases were matched to referents
      according to age, gender, and hospital and personally interviewed for information
      on lifetime job history, smoking habits, passive smoking exposure, cancer in
      relatives, socioeconomic status, and migratory history. The analysis concerned
      industrial titles and occupational categories. With the use of a job-exposure
      matrix, exposure to asbestos, polynuclear aromatic hydrocarbons, arsenic, dust,
      nickel and chromium was assessed. RESULTS: For the men in the 56 industrial and
      122 occupational categories examined, an excess risk of lung cancer was found in
      the machinery industry [odds ratio (OR) 1.62, 95% confidence interval (95% CI)
      1.02-2.55). In pottery manufacturing the risk (OR 2.21, 95% CI 1.00-4.87) was
      increased for workers exposed > or = 10 years (OR 6.43, 95% CI 1.12-37.01).
      Textile workers employed for > or = 10 years with a latency of > or = 40 years
      had an elevated risk (OR 21.93, 95% CI 1.96-245.0). In the analysis using the job
      exposure matrix no risk was detected for the specific lung cancer carcinogens
      examined. For the women, no significantly elevated risk was observed.
      CONCLUSIONS: The results of this study revealed risks of lung cancer for men in
      the machinery industry and for pottery and textile workers with long-term
      exposure.

PMID- 9630061
TI  - Duration of acute exposures to vibration and finger circulation.
AB  - OBJECTIVES: This study investigated changes in finger circulation after different
      durations of exposure to hand-transmitted vibration. METHODS: Finger skin
      temperature (FST), finger blood flow (FBF), and finger systolic blood pressure
      (FSBP) were measured in the middle fingers of both hands of 10 healthy men.
      Finger vascular resistance was also estimated. The right hand was exposed for
      7.5, 15, and 30 minutes (static load 10 N) to 125-Hz vibration (root-mean-square
      acceleration 87 m/s2). Static load only was used as a control. Finger circulation
      was measured before the vibration and static load exposure and at fixed intervals
      during exposure and a 45-minute recovery period. RESULTS: No significant changes
      were found with the static load. The FST and FSBP did not change significantly
      during vibration exposure, whereas vibration produced significant reductions in
      FBF and increases in vascular resistance at each duration when compared with
      preexposure and contralateral (non-vibrated) finger values. Temporary
      vasodilation occurred in the vibrated finger immediately after each vibration
      exposure. Recovery was complete for FBF and vascular resistance after the 7.5
      minute vibration, whereas a progressive FBF reduction occurred in both the
      vibrated and the nonvibrated fingers after 15- and 30-minute exposure. The longer
      the duration of vibration exposure, the stronger the vasoconstriction in the
      vibrated finger during recovery. CONCLUSIONS: Vasoregulatory mechanisms mediated
      by both intrinsic (local) and extrinsic (neural or endocrine) control systems
      seem to be related to digital circulatory changes during 125-Hz vibration. It is
      concluded that, not only the frequency and magnitude of vibration, but also its
      duration contributes to the reaction of the digital vessels to acute vibration.

PMID- 9630060
TI  - Variability in the skin exposure of machine operators exposed to cutting fluids.
AB  - OBJECTIVE: This study describes a new technique for measuring skin exposure to
      cutting fluids and evaluates the variability of skin exposure among machine
      operators performing cyclic (repetitive) work. METHODS: The technique is based on
      video recording and subsequent analysis of the video tape by means of computer
      synchronized video equipment. The time intervals at which the machine operator's
      hand was exposed to fluid were registered, and the total wet time of the skin was
      calculated by assuming different evaporation times for the fluid. The exposure of
      12 operators with different work methods was analyzed in 6 different workshops,
      which included a range of machine types, from highly automated metal cutting
      machines (ie, actual cutting and chip removal machines) requiring operator
      supervision to conventional metal cutting machines, where the operator was
      required to maneuver the machine and manually exchange products. RESULTS: The
      relative wet time varied between 0% and 100%. A significant association between
      short cycle time and high relative wet time was noted. However, there was no
      relationship between the degree of automatization of the metal cutting machines
      and wet time. CONCLUSIONS: The study shows that skin exposure to cutting fluids
      can vary considerably between machine operators involved in manufacturing
      processes using different types of metal cutting machines. The machine type was
      not associated with dermal wetness. The technique appears to give objective
      information about dermal wetness.

PMID- 9630062
TI  - Vibration-induced white finger and cold response of digital arterial vessels in
      occupational groups with various patterns of exposure to hand-transmitted
      vibration.
AB  - OBJECTIVE: This study investigated the relation between vibration exposure, the
      prevalence of white fingers, and the cold response of digital arterial vessels in
      workers using vibrating tools. METHODS: The change in finger systolic blood
      pressure (FSBP) at 15 and 10 degrees C as the percentage of the pressure at 30
      degrees C (FSBP%) was measured in 455 healthy referents and 822 workers exposed
      to hand-transmitted vibration. Exposure to hand-transmitted vibration was
      assessed in terms of 8-hour energy-equivalent frequency-weighted acceleration
      [A(8)] and total operating time with vibrating tools. RESULTS: The prevalence of
      white fingers was 1.1% for the referents and ranged from 9.0% to 51.6% for the
      vibration-exposed groups. The estimated mean value of A(8) ranged between 1.6
      (referents) and 8.3 (quarry drillers) m/s2. After adjustment for age, smoking,
      and drinking habits, the FSBP% was significantly lower in the vibration-exposed
      groups than in the reference group. Groupwise, the FSBP%(10 degrees) was
      inversely related to the prevalence of white fingers, the estimated A(8), and
      total operating time. With FSBP%(10 degrees) <70% or <60% as the lower normal
      limit, the sensitivity of the cold test varied from 86% to 100%, with a
      specificity of 90% to 94%, and a positive predictive value of 68% to 74%.
      CONCLUSIONS: FSBP measurement during cold provocation is a useful laboratory test
      for white fingers. A quantitative relationship between cold-induced digital
      arterial hyperresponsiveness and occupational exposure to hand-transmitted
      vibration was suggested.

PMID- 9630063
TI  - Occupational factors affecting sick leave attributed to low-back pain.
AB  - OBJECTIVES: The purpose of this study was to determine the occupational factors
      that cause workers to take sick leave attributed to low-back pain. METHODS:
      Twice, with a 24-month interval, 117 white- and 189 blue-collar employees from 2
      metal industry companies completed a questionnaire on recurrent low-back pain and
      exposure to potential risk factors (biomechanical loads, physical environment,
      psychosocial factors) at work. Sick leave was monitored for the period between
      the questionnaires. RESULTS: Low-back pain was predicted by exposure to harmful
      biomechanical loads among both white- and blue-collar workers [odds ratio (OR)
      4.1 and 4.7, respectively), stress among white-collar workers (OR 2.4), and draft
      among blue-collar workers (OR 2.3). The take-up of sick leave was predicted by
      exposure to harmful biomechanical loads [rate ratio (RR) 1.7]; for sick leaves
      attributed to low-back pain the rate ratio was 3.1. Lack of recognition and
      respect at work predicted sick leave attributed to low-back pain (RR 2.0), but
      not sick leave attributed to other disorders. CONCLUSIONS: Recurrent low-back
      pain is preceded by reports of harmful biomechanical loads at work among white-
      and blue-collar workers, by stress among white-collar workers and by draft among
      blue-collar workers. The environmental and psychosocial factors under study did
      not modify the relation between biomechanical loads and recurrent low-back pain.
      Sick leave attributed to back disorders is preceded by exposure to biomechanical
      loads at work and by a lack of recognition and respect at work among blue-collar
      workers. Biomechanical loading seems to be the most important occupational factor
      predicting both recurrent low-back pain and sick leave attributed to back
      disorders. Lack of recognition and respect at work appear to affect sick leave
      attributed to back disorders.

PMID- 9630064
TI  - Predictors of blood lead concentrations in the lead-free gasoline era.
AB  - OBJECTIVES: Blood lead concentrations in a Danish reference population were
      related to information from an extensive questionnaire on work, environment, and
      life-style. METHODS: Data were gathered for 209 persons by means of a
      questionnaire and blood lead analyses. RESULTS: The mean concentration of lead in
      blood was 0.167 micromol/l (ie, significantly lower than in previous studies).
      This finding is in accordance with the fact that less than 10% of the gasoline
      used in Denmark contains lead additives (up to 0.15 g/l). An important finding
      was that the well-documented predictors for lead in blood at higher concentration
      levels, such as age, gender, menopausal status, and intake of alcohol, are still
      valid in a low-level exposure situation. In addition, a strong and negative
      correlation was found between blood lead concentrations and dietary
      supplementation with vitamins and minerals. CONCLUSIONS: The present data
      indicate that lead exposure may still constitute a health risk in a small
      proportion of adult men and postmenopausal women.

PMID- 9630065
TI  - Holoprosencephaly: from Homer to Hedgehog.
AB  - Holoprosencephaly (HPE), a common developmental defect affecting the forebrain
      and face, is etiologically heterogeneous and exhibits wide phenotypic variation.
      Graded degrees of severity of the brain malformation are also reflected in the
      highly variable craniofacial malformations associated with HPE. In addition,
      individuals with microforms of HPE, who usually have normal cognition and normal
      brain imaging, are at risk for having children with HPE. Some obligate carriers
      for HPE may not have any phenotypic abnormalities. Recurrent chromosomal
      rearrangements in individuals with HPE suggest loci containing genes important
      for brain development, and abnormalities in these genes may result in HPE.
      Recently, Sonic Hedgehog (SHH) was the first gene identified as causing HPE in
      humans. Proper function of SHH depends on cholesterol modification. Other
      candidate genes that may be involved in HPE include components of the SHH
      pathway, elements involved in cholesterol metabolism, and genes expressed in the
      developing forebrain.

PMID- 9630066
TI  - Overgrowth syndromes and genomic imprinting: from mouse to man.
AB  - Beckwith-Wiedemann syndrome (BWS), a human overgrowth syndrome with a complex
      genetic basis, is caused by alterations to chromosome 11p15, a region subject to
      genomic imprinting. These alterations include translocations, duplications,
      single gene mutations of p57KIP2, and increased expression of insulin-like growth
      factor 2 (IGF2). A phenotypically related X-linked overgrowth syndrome, Simpson
      Golabi Behmel syndrome (SGBS), is caused by alterations in glypican-3 (GPC3), a
      molecule that may interact with the gene products identified to be important in
      generating the BWS phenotype, that is, IGF2 and p57KIP2. The crucial defect in
      these overgrowth syndromes is likely to be an imbalance in contributions of
      growth-promoting genes versus growth-inhibitory genes in critical tissues at
      specific developmental stages. Murine models have been used to study the effects
      of targeted deletions of the genes p57KIP2 and GPC3, as well as overexpression of
      IGF2. At this time, there are still many issues which remain to be explored
      before we can fully understand the molecular basis of BWS and SGBS.

PMID- 9630067
TI  - Duchenne mouse knocked out by two blows.

PMID- 9630068
TI  - The new face of an old villain--cholesterol.

PMID- 9630069
TI  - Defects in the human homolog of Drosophila diaphanous in non-syndromic deafness.

PMID- 9630070
TI  - Implications of genotyping of spouses to limit investigation of children in
      genetic hemochromatosis.
AB  - BACKGROUND: A genetic test for hemochromatosis has allowed for the first time,
      genotypic identification of heterozygotes. The purpose of this study is to
      determine whether genotyping of spouses of homozygotes results in fewer
      investigations of children and subsequent cost savings. METHODS: Two hundred and
      ninety one children of homozygotes were studied using HLA typing, transferrin
      saturation and serum ferritin. Ninety six percent of the probands were homozygous
      for the C282Y mutation of the HFE gene. Pedigrees were reviewed to determine cost
      savings incurred if the spouse had been genotyped to guide follow-up studies in
      the children. Paternity was confirmed by HLA studies. RESULTS: There were 13
      homozygotes identified. All homozygous children tested (10/10) were homozygous
      for the C282Y mutation. There were no iron loaded children identified in
      homozygotes negative for the C282Y mutation. Genotyping of the spouse eliminated
      the need for the investigation of 269 children. The cost savings of this strategy
      were modeled using the cost of the family studies (consultation, iron studies)
      minus the cost of spouse assessment (consultation, genotyping) plus the cost of
      assessment of children in families in which the spouse was a heterozygote. The
      spousal genotyping strategy resulted in a cost savings of 39%. CONCLUSION:
      Genotying the spouse of a homozygote is the best cost-efficient strategy in
      pedigree studies because it leads to more selective investigation of children for
      the hemochromatosis gene.

PMID- 9630071
TI  - DNA diagnosis of FRAXA and FRAXE in Chinese children with neurodevelopmental
      disorders and fragile X syndrome.
AB  - Fragile X (FraX) syndrome is the most common cause of inherited mental
      retardation. To see whether FRAXA or FRAXE can account for the etiology of some
      unexplained neurodevelopmental disorders in children, we screened for
      trinucleotide repeat expansion in a consecutive cohort of 73 Chinese children and
      their mothers seen in 1995 (group 1) referred for developmental assessment due to
      developmental delay, language delay, attention deficit hyperactivity disorder,
      autistic spectrum disorder, mental retardation and/or learning disability. We
      also screened DNA samples of all five previously diagnosed cytogenetically
      positive FraX boys, their mothers and sisters (group 2). A control group of
      unrelated teenagers and adults were recruited from the community (group 3). In
      group 1, 3 families (2 mothers and a mother and her son) were found to carry a
      small premutation allele at FRAXA (premutation frequency = 2%, 3/153 independent
      X chromosomes), but none had any expansion at FRAXE. In group 2, all 5 FraX boys
      had full mutation at FRAXA and normal repeat length at FRAXE. In group 3, 1 male
      has a premutation allele out of 18 males and 59 females tested (premutation
      frequency of control = 0.7%, 1 out of 136 X chromosomes). For FRAXE screening in
      group 3, 2 females were carriers (1.5%, 2 out of 136 X chromosomes). Thus, FRAXA
      and FRAXE cannot account for the etiology of neurodevelopmental disorders in our
      cohort of Chinese children, and the prevalence of FRAXE mutation in normal
      Chinese population appears to be higher than reported in the Caucasians.

PMID- 9630072
TI  - Glucose-6-phosphatase gene (727G-->T) splicing mutation is prevalent in Hong Kong
      Chinese patients with glycogen storage disease type 1a.
AB  - Glycogen storage disease type la (GSD1a) is an autosomal recessive metabolic
      disorder caused by a deficiency in glucose-6-phosphatase (G6Pase). We analyzed
      the G6Pase genes of two unrelated Chinese families with GSD1a. DNA sequencing of
      all five exons and the exon-intron boundaries revealed a G T transversion at
      nucleotide 727 (727G-->T) in exon 5, which has previously been reported to cause
      abnormal splicing. In one family, the subject and her affected sister were
      confirmed to be homozygous for this mutation and their parents to be
      heterozygotes. In the other family, the proband was identified to be heterozygous
      for this mutation, and a novel mutation, the 341delG in exon 2, was identified.
      This mutation alters the reading frame and creates a stop codon TAA 15 codons
      downstream from the mutation, resulting in a truncated protein. Family studies
      revealed that the father was heterozygous for the 727G-->T mutation and that the
      mother was heterozygous for the 341delG mutation. This is the first time that the
      727G T mutation has been found in Chinese patients or outside Japan. Since we
      only tested two GSD1a families and found 727G-->T in both, we believe that this
      mutation may also be prevalent in our local Chinese population. To investigate
      allele frequencies, we screened 385 Chinese healthy volunteers and found two
      asymptomatic carriers. Our findings suggest that the 727G-->T mutation is indeed
      prevalent in Hong Kong.

PMID- 9630073
TI  - Serum lipids and apolipoprotein E phenotypes in identical twins reared apart.
AB  - Lipid and lipoprotein metabolism is controlled by genes, the environment and the
      gene environment interaction. We studied monozygotic twin pairs reared apart
      (MZA) and an age sex matched group of twins reared together (MZT) to evaluate the
      effects of the genotype and the rearing environment on lipids. The intraclass
      correlations for low density lipoprotein (LDL) cholesterol were 0.21 and 0.50 for
      the MZA and MZT groups, respectively, suggesting that the rearing environment
      possibly had an impact on the variability in LDL cholesterol later in life. The
      intraclass correlations for total cholesterol (0.26 and 0.47 for the MZA and MZT
      groups, respectively) reflected those for LDL cholesterol. The intraclass
      correlations for high density lipoprotein (HDL) cholesterol did not show any
      difference between the twin groups, suggesting that the rearing environment does
      not have major long-term effects on the variability of HDL levels. The intrapair
      differences for LDL cholesterol were smallest in the twins heterozygous for the
      apolipoprotein E allele epsilon2 (E2/3 and E2/4 phenotypes), intermediate in the
      pairs with the common E3/3 phenotype and enhanced in the pairs with E4/3
      phenotype. To conclude, these data suggest that the rearing environment may play
      a role in the variability of LDL cholesterol levels, although variance difference
      between MZAs and MZTs, and the small number of available monozygotic twins reared
      apart limits the generalizability of the results.

PMID- 9630074
TI  - The intermediate alleles of the fragile X CGG repeat in patients with mental
      retardation.
AB  - We have analysed the size of the non-expanded FRAXA CGG repeat in 385 male
      patients affected by mental retardation and in 182 unrelated normal chromosomes
      as control. The results show that intermediate alleles with more than 40 repeats
      were not significantly more frequent in patients than in controls. These data do
      not corroborate previous findings supporting the idea that intermediate alleles
      may have a deleterious effect on mental retardation.

PMID- 9630075
TI  - Congenital bilateral absence of vas deferens with a new missense mutation (P499A)
      in the CFTR gene.
AB  - We describe a congenital bilateral absence of the vas deferens (CBAVD) patient
      with a compound heterozygosity in the cystic fibrosis transmembrane regulator
      (CFTR) gene for a stop mutation W1282X and a new missense mutation P499A. The
      P499A is interpreted as a mild mutation whose phenotypic effects, in this case
      limited to the development of wolffian duct derivatives, are revealed only in
      combination with a severe CFTR mutation.

PMID- 9630076
TI  - A novel missense mutation (402C-->T) in exon 1 in the EDA gene in a family with X
      linked hypohidrotic ectodermal dysplasia.
AB  - Hypohidrotic ectodermal dysplasia (EDA), or Christ-Siemens-Touraine syndrome, is
      clinically characterized by hypohidrosis, hypoodontia and hypotrichosis. The X
      linked form of the disease has been mapped to Xq12-q13.1, and a gene from this
      region has recently been cloned. This gene encodes a predicted transmembrane
      protein of 135 amino acids, which was found to be expressed in keratinocytes,
      hair follicles, and sweat glands. A variety of rearrangements in this gene have
      been found in patients with hypohidrotic ectodermal dysplasia. We have screened
      the probands from nine unrelated Danish families with hypohidrotic ectodermal
      dysplasia for mutation in exon 1 of the EDA-gene by polymerase chain reaction
      single strand conformation polymorphism (PCR-SSCP). In one large kindred we
      identified a novel missense mutation (402C-->T), which changes a histidine to
      tyrosine at position 54 in the protein. This mutation cosegregates with the
      disease in the family and is the first mutation described which affects the
      predicted transmembrane, hydrophobic domain of the protein.

PMID- 9630077
TI  - Detection of mtDNA deletion in Pearson syndrome by two independent PCR assays
      from Guthrie card.
AB  - Pearson syndrome is a multisystem juvenile condition associated with deletions in
      the mitochondrial genome. The most common 4977 bp deletion of mitochondrial DNA
      (mtDNA) can mainly be detected in the patients' peripheral blood. Here we report
      a child with a clinically unclarified diagnosis where molecular genetic results
      proved Pearson syndrome from stored dried blood sample 6 months after the
      patient's death. PCR amplification around the breakpoint of the most common mtDNA
      deletion could detect the presence of mutated mtDNA. Another polymerase chain
      reaction (PCR) assay indicated the low level of wild type mtDNA in patients'
      blood. We believe that this case shows the importance of storing Guthrie card and
      the availability of detection of Pearson syndrome from dried blood sample.

PMID- 9630078
TI  - Polymorphisms at the angiotensinogen (AGT) and angiotensin II type 1 receptor
      (AT1R) loci and normal blood pressure.
AB  - The M235T polymorphism at the angiotensinogen (AGT) locus and the A1166C
      polymorphism at the angiotensin II type 1 receptor (AT1R) locus have been
      reported to be associated with hypertension in several populations. We examined
      these polymorphisms in three samples of healthy Norwegians with respect to normal
      blood pressure (BP) levels. None of the genotypes defined by the polymorphisms or
      their combinations were associated with systolic (S) BP (SBP) or diastolic (D) BP
      (DBP) level. However, there was a trend in all three series that individuals
      carrying the C allele of the A1166C polymorphism at the AT1R locus (homozygotes
      as well as heterozygotes) had higher SBP, than AA homozygous individuals. The
      observation did not reach statistical significance in any of the series. When
      examining these two polymorphisms with respect to possible variability gene
      effects on BP in two series of monozygote (MZ) twin pairs, no such effect was
      detected. We could not detect any interaction between the loci studied with
      respect to BP level or variability. Thus, neither the AGT locus nor AT1R locus,
      separately analysed or together, seem to have variability gene effects or
      definite level gene effects on normal BP.

PMID- 9630079
TI  - Deletion of chromosome 3q proximal region gives rise to a variable phenotype.
AB  - We report two new cases with interstitial deletions of chromosome 3. Both had
      breakpoints established as q12q21. Despite an apparently identical abnormal
      karyotype, their phenotypes were different although hypotonia, severe
      developmental delay, lack of speech, high arched palate and pointed chin were
      common features. One patient had corpus callosum agenesis (ACC), also present in
      two of the only four previously reported cases with a deletion in this region.

PMID- 9630080
TI  - Normal growth in Angelman syndrome due to paternal UPD.
AB  - We describe 2 patients with Angelman syndrome (AS) due to paternal uniparental
      disomy (UPD). One patient is a female aged 30 years and the other a male aged 4
      1/2 years. Both have the characteristic wide mouth and big chin, moderate mental
      retardation, virtually no speech but some 30 words of sign language and a happy
      disposition with outbursts of laughter. Ataxia is minimal in both patients,
      manifesting mainly when they are excited or running. Both patients are tall
      (height around 90th percentile), have a head circumference around 75th percentile
      and are overweight (weight over the 97th percentile). These cases add to the
      knowledge of the possibility of normal or increased growth parameters,
      particularly weight, in AS when the genetic mechanism is paternal UPD.

PMID- 9630081
TI  - A highly polymorphic CA/GT repeat (LIMK1GT) within the Williams syndrome critical
      region.

PMID- 9630082
TI  - A novel point mutation associated with alkaptonuria.

PMID- 9630083
TI  - Chimerism detected by an unbalanced chromosome translocation: an alternative
      hypothesis.

PMID- 9630085
TI  - Managing the patient with advanced heart failure. Meeting proceedings of the
      Advanced Heart Failure Group.

PMID- 9630084
TI  - Centromeric alphoid DNA heteromorphisms of chromosome 22 revealed by FISH
      technique.

PMID- 9630086
TI  - Clinical definition and epidemiology of advanced heart failure.

PMID- 9630087
TI  - The pathophysiology of advanced heart failure.

PMID- 9630088
TI  - Current medical therapy for advanced heart failure.

PMID- 9630089
TI  - Current and novel pharmacologic approaches in advanced heart failure.

PMID- 9630090
TI  - Beyond drug therapy: nonpharmacologic care of the patient with advanced heart
      failure.

PMID- 9630091
TI  - Outcomes and costs within a disease management program for advanced congestive
      heart failure.

PMID- 9630092
TI  - Optimizing therapy for complex or refractory heart failure: a management
      algorithm.

PMID- 9630093
TI  - Heart failure associated with preserved systolic function: a common and costly
      clinical entity.

PMID- 9630094
TI  - Advanced congestive heart failure: What do patients want?

PMID- 9630095
TI  - Treatment of chronic mitral regurgitation.
AB  - BACKGROUND: Chronic, severe mitral regurgitation is a common clinical entity that
      can lead to progressive, irreversible left ventricular dysfunction. New
      information on the natural history of this condition, coupled with advances in
      surgical technique, have changed the roles of medical and surgical therapies.
      METHODS: The current medical and surgical literature regarding chronic mitral
      regurgitation is critically reviewed. RESULTS: There is no well-defined role for
      medical therapy in chronic mitral regurgitation. The goal of the treating
      physician is therefore to choose the optimal timing for surgical intervention.
      This process begins with noninvasive quantification of the degree of
      regurgitation. If severe, a careful search for signs or symptoms of impending
      left ventricular dysfunction should follow. Recent advances in surgical
      techniques for mitral valve repair allow for correction of the valvular defect
      with minimal mortality risk and improved preservation of ventricular function and
      are an impetus for early operative intervention. Mitral valve repair may also be
      beneficial in the setting of severe dilated cardiomyopathy. CONCLUSIONS: The
      development of techniques for mitral valve repair has altered the treatment
      paradigm for severe mitral regurgitation. Surgical intervention before the onset
      of left ventricular dysfunction is recommended.

PMID- 9630096
TI  - Sequential changes in cardiac structure and function in patients with Duchenne
      type muscular dystrophy: a two-dimensional echocardiographic study.
AB  - BACKGROUND: Most patients with progressive muscular dystrophy of the Duchenne
      type (DMD) die of respiratory failure at approximately 20 years of age. However,
      some patients with DMD die of heart failure in relatively short periods of time.
      We investigated the long-term progression of cardiac impairment in patients with
      DMD by two-dimensional echocardiography. METHODS: We monitored 74 patients for 4
      years with two-dimensional echocardiography. Patients were classified into four
      groups according to the 8-grade Swinyard-Dever system. We also evaluated the
      echocardiographic features of 22 other patients with DMD with studies performed
      within 1 year before their deaths. RESULTS: During the 4-year follow-up the left
      ventricle expanded, and regional left ventricular wall motion abnormalities
      developed in the posterior wall and apex. Almost all patients had myocardial
      dysfunction that progressed in parallel with their Swinyard-Dever stage. However,
      in a few patients who died of congestive heart failure, left ventricular dilation
      and circumferential left ventricular wall motion were severely impaired.
      CONCLUSIONS: Myocardial impairment is accelerated in patients with DMD who died
      of heart failure. Two-dimensional echocardiography is a useful tool for the early
      diagnosis of left ventricular dysfunction and provides useful information for the
      treatment of patients with DMD.

PMID- 9630097
TI  - Cardiac electrophysiologic effects of norepinephrine in human beings.
AB  - BACKGROUND: The electrophysiologic effects of norepinephrine (NE) in human beings
      have not been previously described. METHODS: The electrophysiologic effects of NE
      infused at a rate of 25 ng/kg/min were determined in 21 patients with a mean age
      of 41 +/- 11 years and without structural heart disease who underwent an
      electrophysiology procedure. In a subgroup of 10 patients electrophysiologic
      parameters were measured at baseline, after the infusion of NE, and after
      administration of beta-blockade while in continuous NE infusion. RESULTS: The
      baseline NE plasma concentration of 298 +/- 153 pg/ml increased to 708 +/- 419
      pg/ml after the infusion of NE. NE significantly increased the mean blood
      pressure, sinus cycle length, corrected sinus node recovery time,
      ventriculoatrial block cycle length, and the atrial and ventricular effective
      refractory periods. In a subset of 10 patients 0.2 mg/kg propranolol administered
      during continued infusion of NE resulted in a further increase in sinus cycle
      length, atrial-His interval, and ventricular refractoriness. CONCLUSION: A
      physiologic elevation in the plasma NE concentration results in a depression of
      sinus node function and atrioventricular conduction and in prolongation of atrial
      and ventricular refractoriness. Some of NE's effects are partially offset by beta
      adrenergic stimulation.

PMID- 9630098
TI  - Correlation of myocardial histologic changes in hibernating myocardium with
      dobutamine stress echocardiographic findings.
AB  - OBJECTIVE: The objective of this study was to correlate histologic changes in
      hibernating myocardium with dobutamine stress echocardiography (DSE). METHODS:
      Patients (n = 8) with anterior regional wall motion abnormalities in the seven
      echocardiographic segments representing the territory supplied by a significantly
      stenosed left anterior descending coronary artery had preoperative DSE performed
      (yielding 56 segments for analysis). Two transmural biopsy specimens were taken
      from the anterior wall of the left ventricle during coronary artery bypass
      grafting. RESULTS: Morphometric histologic analysis of biopsy specimens showed
      significantly less fibrosis in segments demonstrating inotropic reserve (p <
      0.05) and significantly less fibrosis in segments demonstrating improvement in
      wall motion on echocardiography 3 months after revascularization (p < 0.05). DSE
      had a sensitivity of 100% and a specificity of 62% for detection of hibernating
      myocardial segments. Percent fibrosis was inversely correlated with percent
      nucleated cells (r = 0.66, p < 0.01) and directly correlated with cytoplasmic
      clearance (r = 0.76, p < 0.01). CONCLUSION: Inotropic response during DSE
      correlates with histologic evidence of hibernating myocardium.

PMID- 9630099
TI  - Diversity of myocardial involvement in systemic sclerosis: an 8-year study of 95
      Japanese patients.
AB  - BACKGROUND: Myocardial fibrosis has been reported to be an important complication
      of systemic sclerosis (SSc). Left ventricular (LV) hypertrophy has also been
      reported, but its significance is unclear. Correlations between cardiac
      complications and clinical or serologic subsets of SSc have not been previously
      evaluated by long-term observational studies. METHODS: We correlated the findings
      of echocardiography, electrocardiography, and autopsy with clinical and serologic
      features in 95 patients with SSc who were monitored for up to 8 years. RESULTS:
      Septal thickness determined by echocardiography was significantly greater in
      patients with anti-nuclear ribonucleoprotein (nRNP) antibodies than in patients
      with anti-Scl70 or anticentromere antibodies. Fractional shortening was reduced
      in patients with diffuse cutaneous involvement or anti-Scl70 antibodies. Ten
      patients had cor pulmonale, which was confirmed by echocardiography. Four of them
      had diffuse cutaneous involvement and advanced pulmonary fibrosis, whereas four
      had anti-nRNP antibodies and mild or no fibrosis. Septal hypertrophy was detected
      in 12 patients, 10 of whom had limited cutaneous involvement and six had anti
      nRNP antibodies. Diffuse or regional LV wall hypokinesia was seen in seven
      patients, of whom six had anti-Scl70 antibodies and five had diffuse cutaneous
      involvement. Six patients with cor pulmonale, five with abnormal LV wall motion,
      and three with septal hypertrophy died during the follow-up period. Autopsy
      revealed LV hypertrophy in three with septal hypertrophy, disarray and irregular
      hypertrophy of myocytes in one of them, and extensive myocardial fibrosis in one
      with diffuse LV wall hypokinesia. CONCLUSIONS: Septal hypertrophy and cor
      pulmonale caused by pulmonary vasculopathy were associated with limited cutaneous
      involvement or anti-nRNP antibodies, whereas abnormal LV wall motion and cor
      pulmonale caused by advanced pulmonary fibrosis were mostly seen in patients with
      diffuse cutaneous involvement or anti-Scl70 antibodies.

PMID- 9630100
TI  - Three-dimensional echocardiographic evaluation of left ventricular volume:
      comparison of Doppler myocardial imaging and standard gray-scale imaging with
      cineventriculography--an in vitro and in vivo study.
AB  - BACKGROUND: Standard gray-scale imaging (GSI), three-dimensional (3D)
      echocardiography has been shown to be superior to two-dimensional
      echocardiography in measuring left ventricular volume. However, the often
      relatively poor quality of transthoracic gray-scale data can limit the potential
      application of this technique. Doppler myocardial imaging (DMI) is a new
      ultrasound technique that potentially offers higher-quality 3D images with a
      transthoracic approach than the 3D GSI technique. This study was designed to
      compare the accuracy of standard GSI and DMI 3D left ventricular volume
      measurements in vitro and in vivo. METHODS AND RESULTS: In vitro, the minimum and
      maximum volume of the contracting single-chamber, tissue-mimicking phantom was
      calculated by using both techniques. In vivo, GSI and DMI 3D left ventricular
      volume measurements were performed in 16 patients. End-diastolic and end-systolic
      left ventricular volumes were computed for both techniques and compared with
      those calculated by cineventriculography. In vitro, both methods tended to
      underestimate the true phantom volume, but the systematic error was smaller for
      DMI than for GSI (-1.2% +/- 1.5% vs. -4.3% +/- 3%; p < 0.01) and was more
      constant in the case of DMI over the range of different sizes of true volume. In
      vivo, for GSI the end-diastolic volume mean difference was -12.6 ml and the
      limits of agreement were +/-18 ml, and for DMI the corresponding values were -4.2
      and +/- 10.6 ml, respectively. The difference for end-systole was -6.5 +/- 10.6
      ml and -1.5 +/- 10 ml for GSI and DMI, respectively. The magnitude of the
      difference in volume measurement between 3D echocardiography and
      cineventriculography was significantly smaller when using the Doppler technique.
      CONCLUSIONS: The results of this in vitro and in vivo study indicate that DMI is
      superior to GSI as a transthoracic acquisition technique for 3 D volume
      computation.

PMID- 9630101
TI  - Noninvasive assessment of transplant-associated arteriosclerosis.
AB  - BACKGROUND: Transplant-associated arteriosclerosis is the major limitation to
      long-term survival in the cardiac transplant recipient, and annual surveillance
      angiography is used in many centers to monitor its progression. Noninvasive
      methods would be preferable because angiography is invasive, costly, and
      insensitive; however, the reliability of such methods has been questioned.
      METHODS: All publications relating to the assessment of the cardiac allograft by
      noninvasive testing were identified through MEDLINE and a review of references
      from the published literature on transplant-associated arteriosclerosis. RESULTS:
      Resting and stress ECG, radionuclide scintigraphy, echocardiography, and positron
      emission tomography have all been used in cardiac transplant recipients with
      variable results. Most techniques are insensitive, but this limitation may be
      improved with pharmacologic stress imaging like dobutamine echocardiography.
      Although insensitive, some methods have good specificity (i.e., radionuclide
      scintigraphy). The noninvasive measurement of absolute coronary blood flow is
      promising as a specific and sensitive technique but is limited by availability
      and cost. CONCLUSIONS: In general, noninvasive techniques to assess transplant
      associated coronary arteriosclerosis are limited by variable sensitivity and
      specificity. However, certain methods, such as dobutamine echocardiography and
      radionuclide scintigraphy, can provide important adjunctive physiologic
      information to angiography. Such techniques can therefore help to guide the care
      and treatment of the cardiac transplant recipient with allograft coronary
      arteriosclerosis.

PMID- 9630102
TI  - Relation between single tomographic intravascular ultrasound image parameters and
      intracoronary Doppler flow velocity in patients with intermediately severe
      coronary stenoses.
AB  - BACKGROUND: Intravascular ultrasound (IVUS) imaging parameters have been
      suggested as criteria to determine coronary lesion significance before
      intervention. However, there has not been a systematic examination of combined
      anatomic and physiologic data in the same patients with coronary artery disease.
      METHODS AND RESULTS: To examine the relation between coronary flow reserve and
      IVUS parameters, 41 patients with intermediately severe coronary artery stenoses
      had measurements of coronary flow velocity (0.014-inch Doppler flow wire),
      coronary flow velocity reserve (CVR) (hyperemic/basal mean flow), IVUS imaging
      (2.9F, Cardiovascular Imaging Systems, Inc.), and quantitative coronary
      angiography before intervention. Correlations between physiologic and anatomic
      parameters were performed by simple regression. Results were also examined by
      patient subgroups with CVR > 1.8 or < 1.8 to assess differences in IVUS
      parameters. The angiographic percent diameter stenosis was 52% +/- 17% (range 18%
      to 95%). Mean CVR was 1.88 +/- 0.56 (range 0.9 to 3.18). IVUS minimal luminal
      diameter (r = 0.312, p = 0.047) and angiographic percent stenosis (r = 3.05, p =
      0.052) were weakly related to poststenotic CVR. Comparing patients with CVR <
      1.8, IVUS reference segment area, IVUS lumen area, and angiographic percent
      diameter stenosis was higher (17.7 +/- 0.3 vs 12.9 +/- 4.4 mm2, p < 0.05; 6.20 +/
      3.76 vs 4.34 +/- 2.00 mm2, p < 0.05; and 60% +/- 14% vs 46% +/- 17%, p < 0.01,
      respectively) than in the group with CVR > 1.8. CONCLUSIONS: Despite a precise
      determination of cross-sectional vessel areas and absolute dimensions by IVUS,
      single tomographic measurements did not correlate well with coronary physiologic
      responses. These data suggest that the physiologic data may be complementary to
      anatomic quantitative IVUS, enhancing information for coronary interventional
      decision making.

PMID- 9630103
TI  - Quantification of the aortic valve area in three-dimensional echocardiographic
      data sets: analysis of orifice overestimation resulting from suboptimal cut-plane
      selection.
AB  - BACKGROUND: Our study was designed to determine the feasibility of three
      dimensional echocardiographic (3DE) aortic valve area planimetry and to evaluate
      potential errors resulting from suboptimal imaging plane position. METHODS AND
      RESULTS: Transesophageal echocardiography with acquisition of images for 3DE was
      performed in 27 patients. Aortic valve orifice was planimetered in two
      dimensional echocardiograms (2DE) and in two-dimensional views reconstructed from
      3DE data sets optimized for the level of the cusp tips. To evaluate the errors
      caused by suboptimal cut-plane selection, orifice was also measured in cut-planes
      angulated by 10, 20, and 30 degrees or shifted by 1.5 to 7.5 mm. Planimetered
      orifice areas was similar in 2DE and 3DE studies: 2.09 +/- 0.97 cm2 versus 2.07
      +/- 0.92 cm2. Significant overestimation was observed with cut-plane angulation
      (0.09, 0.19, and 0.34 cm2 at 10 degree increments) or parallel shift (0.11, 0.22,
      0.33, 0.43, and 0.63 cm2 at 1.5 mm increments). Three-dimensional
      echocardiographic measurement reproducibility was very low and superior to that
      of 2DE. CONCLUSIONS: Three-dimensional echocardiography allows accurate aortic
      valve area quantification with excellent reproducibility. Relatively small
      inaccuracy in cut-plane adjustment is a major source of errors in aortic valve
      area planimetry.

PMID- 9630104
TI  - Heart rate variability during the first month of smoking cessation.
AB  - BACKGROUND: Heart rate variability (HRV) is known to increase after smoking
      cessation. However, no work has been performed concerning HRV immediately after
      smoking cessation. METHODS AND RESULTS: We studied HRV before and from 1 day to 1
      month after smoking cessation and also determined whether there is a relation
      between HRV and the withdrawal syndrome immediately after smoking cessation. We
      determined HRV by using a two-channel 24-hour ambulatory ECG system before and 1,
      2, 3, 7, 14, 21, and 28 days after smoking cessation in 20 healthy male
      volunteers who had smoked one or more packs per day for 2 or more years. One day
      after smoking cessation, heart rate decreased significantly, and all 24-hour time
      and frequency domain indices of HRV increased except the standard deviations of
      the normal R-R intervals and the 5-minute mean R-R. The magnitude of increase in
      these indices peaked 2 to 7 days after smoking cessation and gradually decreased
      thereafter. The increase in HRV persisted 1 month after smoking cessation. In the
      16 subjects with signs of withdrawal syndrome and in the four subjects without
      evidence of withdrawal before and immediately and 1 month after smoking
      cessation, HRV increased immediately after smoking cessation and remained
      elevated after 1 month. CONCLUSIONS: HRV increases immediately after smoking
      cessation and gradually declines thereafter, which suggests that the effect of
      smoking on autonomic activity rapidly disappears immediately after smoking
      cessation. HRV remained unaffected by the presence or absence of the withdrawal
      syndrome.

PMID- 9630105
TI  - Analysis of the cardiac rhythm preceding episodes of paroxysmal atrial
      fibrillation.
AB  - AIMS: This study seeks to elucidate whether there was a common mode of initiation
      of paroxysmal atrial fibrillation (PAF) episodes that might suggest new
      therapies. METHODS: A library of 177 digitized and analyzed 24-hour Holter
      recordings from PAF pharmacotherapy trials was studied. All noise-free PAF
      episodes > or =0.5 minutes were identified. PAF episodes and the preceding 2
      minutes of sinus rhythm were printed as tachograms and visually inspected. Heart
      rate and ectopic beat behavior were used to characterize modes of PAF onset by
      comparing half-minute segments of the final 2 minutes of sinus rhythm. RESULTS:
      Thirty-four recordings (from 19 patients, aged 61.7 +/- 11.5 years) provided 231
      PAF episodes suitable for analysis. No patients had a consistent mode of PAF
      onset. This was confirmed by systematic analysis of the five patients with the
      most episodes. Overall, a highly significant increase in ectopic beats, from 1.34
      to 6.52 min(-1) (p < 0.001) was found, but heart rate did not significantly
      change (mean heart rate at onset = 64 beats/min). PAF was initiated by a solitary
      ectopic beat in more than half of the cases. No consistent evidence for short
      long-short sequences, seen in ventricular arrhythmias, was found. CONCLUSION: The
      mode of onset of atrial fibrillation is inconsistent, both across a population
      with PAF and within individuals. This has implications for understanding the
      mechanisms of atrial fibrillation onset in human beings and for the treatment of
      the disorder.

PMID- 9630106
TI  - Assessment of left atrial appendage function after cardioversion of atrial
      fibrillation: relation to left atrial mechanical function.
AB  - Although several flow patterns in the left atrial appendage have been described,
      mechanical determinants of its function have not been elucidated in human beings.
      We attempted to investigate changes in left atrial appendage function after
      cardioversion of atrial fibrillation and examine the potential relation between
      appendage function and left atrial mechanical function. Twenty patients without
      mitral valvular disease underwent transesophageal and transthoracic
      echocardiography at 24 hours and 1 week after cardioversion of atrial
      fibrillation. Left atrial appendage function was assessed by the pulsed Doppler
      measurements of left atrial appendage emptying and filling velocities
      corresponding to early and late ventricular diastole, respectively. Left atrial
      mechanical function was evaluated by the transmitral A-wave velocity, percent
      atrial contribution of the total left ventricular filling (percent atrial
      filling), and the pulmonary venous A-wave velocity. Left ventricular function was
      also estimated with conventional M-mode echocardiography. The late appendage
      emptying and filling velocities markedly increased during 1 week after
      cardioversion (p < 0.0001, respectively). This finding was associated with an
      increase in left atrial mechanical function. Changes in the late emptying and
      filling velocities significantly correlated with changes in the transmitral A
      wave velocity (r = 0.59, p < 0.01), percent atrial filling (r = 0.61, p < 0.005),
      and the pulmonary venous A-wave velocity (r = 0.56, p < 0.05). In contrast,
      little change was observed in the early emptying and filling velocities. There
      was no relation between the indexes of left ventricular function and those of
      appendage function. In conclusion, unless there was an alteration of the loading
      conditions, left atrial appendage function improved over several days after
      cardioversion, and its function was related to left atrial mechanical function.

PMID- 9630107
TI  - Multivariate associates of QT dispersion in patients with acute myocardial
      infarction: primacy of patency status of the infarct-related artery. TEAM-3
      Investigators. Third trial of Thrombolysis with Eminase in Acute Myocardial
      Infarction.
AB  - BACKGROUND: QT dispersion (QTd; QT interval maximum minus minimum) has been shown
      to reflect regional variations in ventricular repolarization and is increased in
      patients with life-threatening ventricular arrhythmias. METHODS: To determine
      correlates of QTd in patients who had had myocardial infarction (MI), 207
      patients (158 men, aged 57 +/- 11 years) with acute MI who were treated with
      alteplase or anistreplase within 2.7 +/- 0.9 hours of symptom onset were studied.
      Angiograms at a median of 27 hours after thrombolysis showed reperfusion
      (Thrombolysis in Myocardial Infarction grade > or =2) in 184 (88%) patients. QT
      was measured in 10 +/- 2 leads on discharge electrocardiograms with a
      computerized analysis program interfaced with a digitizer. Associations of QTd
      with 24 variables related to patient characteristics, acute MI, angiography,
      interventions, and radionuclide ventriculography were evaluated by univariate and
      multivariate regression. RESULTS: Univariate associations with QTd (p < or =
      0.10) were Thrombolysis in Myocardial Infarction flow grade 0/1 versus 2/3 (QTd =
      75 +/- 33 msec vs 53 +/- 22 msec, p < 0.0001), minimal luminal diameter (p =
      0.007), left ventricular ejection fraction at discharge (p = 0.007), reinfarction
      (p = 0.01), number of leads with ST elevation (p = 0.05), end-systolic volume at
      discharge (p = 0.04), time to peak creatine kinase (p = 0.06), and YST elevation
      (p = 0.10). Independent associates of QTd were Thrombolysis in Myocardial
      Infarction grade 0/1 versus 2/3 (p < 0.0001), reinfarction (p = 0.005), and
      ejection fraction (p = 0.02). CONCLUSIONS: Successful thrombolysis is associated
      with less QTd in patients after acute MI. Our results support the hypothesis that
      QTd after MI depends on reperfusion status, reinfarction, and left ventricular
      function. Reduction in QTd may be an additional mechanism by which the benefit of
      thrombolytic therapy is realized.

PMID- 9630108
TI  - Single-lead VDD pacing: long-term experience with four different systems.
AB  - BACKGROUND: Previous multicenter studies have shown that single-lead VDD pacing
      systems provide satisfactory atrial-triggered ventricular pacing at middle term
      for treatment of atrioventricular block without sinus dysfunction. However, we
      lack data on long-term results obtained with different VDD systems implanted in a
      large number of patients from a single center. METHODS: One hundred fifty
      patients (76 +/- 11 years) with second- or third-degree atrioventricular block (n
      = 147) or symptomatic hypertrophic cardiomyopathy (n = 3) without sinus
      dysfunction were paced with four different VDD pacing systems able to sense the
      atrium and to pace the ventricle. Atrioventricular synchronization was assessed
      during follow-up by ECG and Holter monitoring. RESULTS: Mean value of the atrial
      electrogram during implantation was 2.01 +/- 0.94 mV without any differences
      among the four systems. With a mean follow-up of 24 +/- 11 months, 95% of
      patients remain paced in VDD mode, whereas 5% have been reprogrammed in VVI or
      VVIR mode for permanent atrial fibrillation or loss of atrial sensing; 96% of
      patients with sinus atrium have atrioventricular synchronization >90% and 94% of
      patients have >95%, without significant difference between the four systems used.
      CONCLUSIONS: These different single-lead VDD systems can provide satisfactory
      long-term atrioventricular synchronization; results are comparable to those
      obtained with conventional DDD pacing systems with two leads.

PMID- 9630109
TI  - N-terminal proANF in acute atrial fibrillation: a biochemical marker of atrial
      pressures but not a predictor for conversion to sinus rhythm. Digitalis in Acute
      Atrial Fibrillation (DAAF) Trial group.
AB  - BACKGROUND: Atrial filling pressures are increased in acute atrial fibrillation,
      which stimulates the release of atrial natriuretic factor pro-hormone, proANF.
      METHODS: In a randomized trial comparing digoxin with placebo in 216 patients, we
      investigated whether the baseline plasma level of N-terminal proANF is a
      predictor for conversion to sinus rhythm and the relation among N-terminal
      proANF, conversion to sinus rhythm, and changes in heart rate. RESULTS: N
      terminal proANF was increased at baseline and decreased significantly in patients
      converting to sinus rhythm, whereas it was mainly unchanged in nonconverters. N
      terminal proANF was not a predictor of conversion to sinus rhythm. A relation was
      found between relative changes in heart rate and N-terminal proANF in
      nonconverters. CONCLUSION: The level of N-terminal proANF does not predict
      conversion to sinus rhythm, which indicates that hemodynamics per se is not
      important. There is a correlation between relative changes in heart rate and N
      terminal proANF in nonconverters.

PMID- 9630110
TI  - Suppression of inducible ventricular tachycardia by ibutilide in patients with
      coronary artery disease. Ibutilide Investigators.
AB  - BACKGROUND: Recent studies suggest that class III antiarrhythmic agents may have
      enhanced efficacy in the treatment of ventricular tachycardia. This study
      describes the first clinical assessment of the new class III agent ibutilide to
      suppress inducible monomorphic ventricular tachycardia (VT) in human beings.
      METHODS AND RESULTS: Fifty-five patients with coronary artery disease and
      inducible sustained monomorphic VT at baseline received either low (0.005 mg/kg +
      0.001 mg/kg, load and maintenance infusion, respectively), middle (0.01 mg/kg +
      0.002 mg/kg), or high dose (0.02 mg/kg + 0.004 mg/kg) infusions of ibutilide
      followed by repeat programmed ventricular stimulation. The mean age of the study
      group was 65.5 +/- 9.5 years and mean left ventricular ejection fraction was 36%
      +/- 11%. Of 48 evaluable patients, 21 (44%) were rendered noninducible after
      ibutilide, with no difference in efficacy among the three dosing groups (p =
      0.83). Ventricular effective refractory periods, QTc interval, and ventricular
      monophasic action potential duration were prolonged over baseline at all tested
      cycle lengths. The QTc and action potential prolongation were dose related.
      Serious drug-related adverse reactions included sustained polymorphic VT in two
      patients (3.6%), spontaneous monomorphic VT in one patient (1.8%), heart block in
      one patient (1.8%), and hypotension in one patient (1.8%). CONCLUSIONS: Ibutilide
      prolongs ventricular repolarization in human beings and demonstrates efficacy in
      suppressing inducible monomorphic VT. Significant cardiovascular side effects
      occurred in 12.7% of patients.

PMID- 9630111
TI  - Coronary artery disease in diabetic and nondiabetic patients with lower extremity
      arterial disease: A report from the Coronary Artery Surgery Study Registry.
AB  - OBJECTIVE: Patients with lower extremity arterial disease (LEAD) are at an
      increased risk of having coronary artery disease (CAD). Diabetics are at
      especially high risk for having LEAD with concomitant CAD. This study was
      undertaken (1) to define the clinical and arteriographic features associated with
      CAD among diabetics and nondiabetics with LEAD and (2) to determine the long-term
      survival and predictors of mortality of diabetics and nondiabetics with LEAD and
      CAD. RESEARCH DESIGN AND METHODS: Two hundred sixty-three diabetics and 1137
      nondiabetics from the Coronary Artery Surgery Study who had evidence of LEAD, who
      were 50 years and older, and who had arteriographically proven CAD were monitored
      for a mean of 12.8 years. RESULTS: Among all the subjects with LEAD there was a
      high prevalence of current and past smoking, history of previous myocardial
      infarction, systemic hypertension, congestive heart failure, high degrees of
      angina pectoris and unstable angina pectoris, and use of beta-blockers. On
      arteriographic evaluation a high prevalence of three-vessel epicardial coronary
      disease and involvement of multiple coronary segments with > or =50% diameter
      narrowing was found. Multivariate analysis showed the number of coronary segments
      with >50% occlusion, the presence of cerebrovascular disease, the use of
      digitalis, and elevated systolic blood pressure were independently associated
      with diabetes. On follow-up diabetics had a significantly higher mortality rate
      (mostly cardiac) than nondiabetics: median survival, 8.1 years and 12.7 years,
      respectively. At 15 years the mortality rates were 77.1% and 62.0%, respectively.
      On multivariate analysis, age, number of coronary occlusions, number of
      significantly narrowed epicardial arteries, diminished myocardial contractility,
      hypertension, and smoking were significant predictors of mortality in the total
      group and in each subgroup. Coronary artery bypass grafting surgery was
      protective. The presence of diabetes was an independent risk factor for
      mortality. CONCLUSIONS: The presence of LEAD is associated with multivessel
      epicardial and multiple coronary segment occlusion. On long-term follow-up there
      is a high mortality rate. In patients with LEAD and diabetes, CAD is especially
      severe and prognosis is poor.

PMID- 9630112
TI  - Enhancement of spatial orientation of intravascular ultrasound images with side
      holes in guiding catheters.
AB  - BACKGROUND: Intravascular ultrasound (IVUS) images are typically viewed and
      recorded in an arbitrary rotational orientation. This study was performed to
      validate a new method for improved orientation of sonographic vascular cross
      sections. METHODS AND RESULTS: We have tested a simple technique for rotational
      indexing of IVUS in cases in which guiding catheters with side holes are used.
      Although guiding catheters are opaque to ultrasonography, the side holes transmit
      the beam and therefore can be easily identified. The orientation of the side
      holes, which is characteristic for each make of guiding catheter, can be used to
      determine the anatomically appropriate rotational orientation of the IVUS image.
      In this study images of four commercially available side-hole guiding catheters
      were viewed in vitro to confirm the visibility of the side holes and to
      characterize their orientation for purposes of rotational orientation of images.
      Feasibility tests of rotational orientation based on side holes were then
      performed in canine coronary arteries (n = 3) and in six human coronary arteries.
      Three serial imaging runs in each clinical case yielded a mean variability in
      rotational orientation of 7.5 +/- 1.5 degrees. CONCLUSION: Validation testing of
      the side-hole technique demonstrates the potential for consistent and
      anatomically appropriate orientation of intravascular ultrasound images.

PMID- 9630113
TI  - Comparison of ionic and nonionic low osmolar contrast media in relation to
      thrombotic complications of angioplasty in patients with unstable angina.
AB  - BACKGROUND: Acute complications of percutaneous transluminal coronary angioplasty
      (PTCA) are more common in patients with unstable coronary syndromes. The
      objective of this study was to prospectively determine the differences between
      ionic and nonionic low osmolar contrast media (LOCM) on potential risk of acute
      complications, particularly abrupt vessel closure, in patients with unstable
      angina undergoing PTCA. METHODS: A total of 210 patients with 278 lesions were
      randomized to receive either ionic or nonionic LOCM during PTCA. Quantitative
      coronary angiographic measurements and assessment of filling defects were made by
      experienced observers who were blinded to the type of contrast media used.
      RESULTS: The baseline clinical and angiographic characteristics, the immediate
      postangioplasty results, and clinical outcome were similar in both groups.
      Subacute recoil, defined as the difference between minimal luminal diameter (in
      millimeters) at 0 and 15 minutes after angioplasty, was significantly greater in
      patients receiving nonionic LOCM (0.17 +/- 0.36 mm vs 0.07 +/- 0.18 mm, p =
      0.004). A filling defect abnormality attributable to dissection, thrombus, or a
      combination of the two was noted in similar proportions of the two groups.
      Although nonsignificant, more thrombus was noted in the nonionic group (21 of 129
      vs 15 of 141, p = NS). The abrupt vessel closure rate was similar in the two
      groups and was only 1.9% in the first 24 hours. However, 17 (8.3%) patients had a
      repeat PTCA at 15 minutes (9 ionic vs 8 nonionic). CONCLUSION: In patients with
      unstable angina the choice of ionic or nonionic LOCM does not appear to
      significantly affect the clinical outcome of PTCA.

PMID- 9630114
TI  - Long-term angiographic prognosis of lesions dilated by coronary angioplasty.
AB  - BACKGROUND: To examine the long-term outcome of coronary angioplasty, lesions
      that remained patent after 3 to 12 months were monitored angiographically at 3
      year intervals. There were 252 lesions successfully dilated (from 83% +/- 13%
      preprocedural stenosis to 19% +/- 14% residual stenosis) between 1983 and 1986
      that remained patent on follow-up angiography (23% +/- 15% stenosis) and were
      monitored further at our outpatient department. METHODS AND RESULTS: Repeat
      angiography was done for 186 lesions at 2 to 4 years and showed that 179 were
      patent (0% to 50% stenosis), one had mild stenosis (55% to 70% stenosis), and six
      had severe stenosis (75% to 100% stenosis). Angiography was repeated for 138
      lesions at 5 to 7 years, showing that 127 were patent, four had mild stenosis,
      and seven had severe stenosis. Finally, angiography was performed for 78 lesions
      at 8 to 10 years, showing that 63 were patent, four had mild stenosis, and 11 had
      severe stenosis. CONCLUSIONS: Although numerous lesions were lost to follow-up,
      most appeared to remain patent for 4 years, after which a significant number
      developed restenosis.

PMID- 9630115
TI  - Factors affecting the prognosis of Ebstein's anomaly during fetal life.
AB  - BACKGROUND: The echocardiographic criteria that have been used to evaluate
      severity of Ebstein's anomaly in utero are the same as those applied after birth.
      OBJECTIVE: The objective of this study was to establish prognostic criteria that
      take into account the peculiarities of the fetal hemodynamics. METHOD: The video
      recordings of eight fetuses with Ebstein's anomaly were retrospectively reviewed.
      RESULTS: The following indexes had no prognostic significance either on fetal or
      neonatal outcome: the ratio of functional tricuspid opening over the diameter of
      the annulus, the degree of displacement of the tricuspid valve opening, and the
      degree of tricuspid regurgitation. The index of severity (based on the surfaces
      of right atrium + atrialized right ventricle) and the cardiothoracic ratio had a
      significant impact only on neonatal survival. The smallest fossa ovalis were
      found in two fetuses who had hydrops. Fetuses who reached term without problems
      had higher left ventricular outputs. A positive linear correlation was found
      between the z score of the left ventricular output and the size of the fossa
      ovalis (r = 0.81, p < 0.05). CONCLUSION: The prognosis of Ebstein's anomaly
      during fetal life is not influenced by criteria described for postnatal life and
      may be related to factors that control the volume load of the left ventricle.

PMID- 9630116
TI  - Serial Doppler echocardiographic evaluation of Carpentier-Edwards pericardial
      valve dysfunction: comparison with Ionescu-Shiley valve.
AB  - BACKGROUND: Doppler echocardiography is a valuable noninvasive method for
      evaluating of the occurrence and degree of either prosthetic valve stenosis or
      regurgitation. By using serial Doppler echocardiographic examination, we
      evaluated the incidence and the mode of the Carpentier-Edwards pericardial valve
      (CEPX) dysfunction compared with that of the Ionescu-Shiley valve (IS). METHODS
      AND RESULTS: After aortic and/or mitral valve replacement, 80 patients with CEPX
      and 111 with IS underwent Doppler echocardiography at intervals of at least 2
      years after surgery. The average durations of follow-up were 6.1 +/- 2.9 years
      for patients with CEPX and 7.2 +/- 3.0 years for those with IS. Bioprosthetic
      valve stenosis was defined as reduced excursion of the bioprosthetic valve
      leaflets and peak gradient > or =60 mm Hg after aortic valve replacement and mean
      gradient > or =7 mm Hg after mitral valve replacement. Bioprosthetic valve
      regurgitation caused by bioprosthetic valve dysfunction was defined as grade > or
      =3 transvalvular regurgitation. In the aortic position, although there was no
      significant difference in the actuarial rate of freedom from bioprosthetic valve
      stenosis between patients with IS and those with CEPX (10 years after surgery,
      88% +/- 7% vs 90%, NS), bioprosthetic regurgitation caused by bioprosthetic valve
      dysfunction occurred less frequently in patients with CEPX than in those with IS
      (10 years after surgery, 86% vs 54% +/- 9%, p < 0.05). In the mitral position,
      bioprosthetic valve stenosis occurred more frequently in patients with CEPX than
      in those with IS (10 years after surgery, 54% +/- 11% vs 72% +/- 8%, p < 0.01).
      Although grade > or =3 transvalvular bioprosthetic regurgitation occurred later
      in patients with CEPX than in those with IS, there was no significant difference
      in the actuarial rate of freedom from that regurgitation between patients with
      CEPX and those with IS (10 years after surgery, 63% +/- 10% vs 54% +/- 7%, NS).
      CONCLUSIONS: For aortic valve replacement, CEPX has good long-term durability
      because of the low incidence of bioprosthetic regurgitation. For mitral valve
      replacement, long-term durability of CEPX is poor, although medium-term
      durability is satisfactory.

PMID- 9630117
TI  - Independent prognostic value of the extent and severity of systolic wall
      thickening abnormality at infarct site after thrombolytic therapy.
AB  - BACKGROUND: The prognostic value of systolic wall thickening abnormality after
      acute myocardial infarction in the thrombolytic era is not clearly known. METHODS
      AND RESULTS: Accordingly, 119 consecutive patients with acute myocardial
      infarction who underwent thrombolysis were investigated with exercise
      electrocardiography and rest echocardiography at predischarge evaluation and were
      followed up for cardiac events. During a mean follow-up period of 19 months, 43
      patients had cardiac events. Multivariate analysis with clinical, exercise
      electrocardiographic, and rest echocardiographic parameters showed that the
      independent predictors of cardiac events were systolic wall thickening score at
      the site of infarct (p = 0.02), end-systolic volume (p = 0.03), and exercise time
      (p = 0.02). The only independent predictor for both recurrent ischemic (death,
      unstable angina, and reinfarction) and nonischemic events (congestive heart
      failure and ventricular tachycardia) was systolic wall thickening score at the
      site of infarct (p = 0.02 and p = 0.007, respectively). CONCLUSIONS: Systolic
      wall thickening abnormality at rest is an important independent predictor of
      cardiac events in patients who have undergone thrombolysis after acute myocardial
      infarction.

PMID- 9630118
TI  - Session highlights from the American College of Cardiology Scientific Sessions:
      March 29 to April 1, 1998.

PMID- 9630119
TI  - A new tool for population-based quality-adjusted life years?

PMID- 9630120
TI  - Toward consistency in cost-utility analyses: using national measures to create
      condition-specific values.
AB  - OBJECTIVES: The authors developed an "off-the-shelf" source of health-related
      quality of life (HRQL) scores for cost-effectiveness analysts unable to collect
      primary data. METHODS: The authors derived and conducted preliminary validation
      on a set of health-related quality of life scores for chronic conditions using
      nationally representative data from the National Health Interview Survey (NHIS)
      and the Healthy People 2000 Years of Healthy Life measure developed to monitor
      the health (longevity and health-related quality of life) of Americans during
      this decade. The measure comprises two domains, role function and self-rated
      health, and is scaled from 0 (death) to 1 (best health state). Health-related
      quality of life scores for chronic conditions were calculated using the Years of
      Healthy Life scores associated with chronic conditions reported in the 1987-1992
      National Health Interview Survey. Preliminary validation was examined by
      comparing the health-related quality of life scores with those obtained in two
      other studies. RESULTS: Tables provide health-related quality of life scores for
      persons with and without conditions. The scores had reasonable face validity,
      ranging from 0.87 for allergic rhinitis to 0.27 for hemiplegia. Correlations of
      the health-related quality of life condition weight scores with those from two
      other studies were 0.78 and 0.86. CONCLUSIONS: These condition weights may prove
      useful to investigators conducting cost-effectiveness analyses using secondary
      data, where community ratings of health-related quality of life for chronic
      conditions are required. Use of a standard set of health-related quality of life
      weights gathered from a national sample can enhance the comparability of cost
      effectiveness analyses. Improvements in national data collection techniques, with
      empirical gathering of preferences, will further strengthen this measure.

PMID- 9630121
TI  - The Veterans Affairs medical care system: hospital and clinic utilization
      statistics for 1994.
AB  - OBJECTIVES: The authors describe the role the Veterans Affairs (VA) medical
      system plays as a provider of clinic and hospital services by examining
      utilization levels and users' characteristics. METHODS: The Veterans Affairs
      hospital discharge database, the Veterans Affairs outpatient clinic files, and
      the veteran population files were used to estimate the number of persons using
      the Veterans Affairs medical care system in 1994 and the intensity of their
      clinic and hospital use. Demographic and clinical characteristics of users were
      tabulated. RESULTS: In 1994, 2.7 million veterans, 10.3% of all US veterans, and
      approximately 23% of veterans who would have met the statutory eligibility
      requirements for Veterans Affairs care, used the hospital and/or clinic
      components of the Veterans Affairs medical system. Sixty-three percent of the
      system's users were younger than age 65, and 10.5% were women. These 2.7 million
      veterans had 901,665 Veterans Affairs hospital stays, 15.5 million bed-days, and
      31.2 million outpatient visits in fiscal year 1994. The average number of
      hospitalizations per hospital user was 1.71; the average number of visits per
      clinic user was 11.7. Medical, surgical, and psychiatric diagnosis-related groups
      (DRGs) accounted for 56%, 21%, and 23%, respectively, of hospitalizations, but
      psychiatric diagnosis-related groups accounted for 43% of all inpatient days.
      Principal medicine clinic visits and psychiatry clinic visits accounted for 21%
      and 16% of Veterans Affairs ambulatory care. CONCLUSIONS: Because the patient
      population served by the Veterans Affairs system is skewed in a number of ways,
      its contribution as a provider of health services in the United States varies by
      gender, age, socioeconomic status, and diagnosis.

PMID- 9630122
TI  - Factors related to potentially preventable hospitalizations among the elderly.
AB  - OBJECTIVES: The authors examine whether the odds of having a hospitalization
      associated with an ambulatory care sensitive condition can be explained by
      observed differences in a Medicare beneficiary's predisposing, enabling, and need
      characteristics. METHODS: A multivariate cross-sectional analysis of Medicare's
      administrative inpatient claims data and the Medicare Current Beneficiary Survey
      was conducted on a nationally representative sample of Medicare beneficiaries.
      Each Medicare beneficiary's hospital utilization was classified into one of three
      categories: (1) no hospital admissions; (2) hospitalized, but no hospitalizations
      for a potentially preventable condition; and (3) at least one potentially
      preventable hospitalization. RESULTS: The results suggest that being older,
      black, or living either in a core standard metropolitan statistical area (SMSA)
      county or a rural county significantly increases the odds of a preventable
      hospitalization, whereas having attended college, or having only Medicare
      insurance coverage reduces the odds of a preventable hospitalization. Further,
      those individuals who assess their health status as poor, have had coronary heart
      disease, a myocardial infarction, or diabetes, and required assistance with two
      or more of the six basic activities of daily living are at a greater risk of a
      preventable hospitalization. CONCLUSIONS: Policy efforts aimed at reducing the
      number of preventable hospitalizations among the elderly should address the
      complex health care delivery needs of those Medicare beneficiaries who have
      special health care needs because they are very old, black, live in core SMSA or
      rural counties, have poor overall health status, and have physical limitations.
      Efforts to reduce the number of Medicare beneficiaries who experience a
      preventable hospitalization may be cost-effective as these beneficiaries may
      account for up to 17.4% of Medicare's reimbursement for inpatient, outpatient,
      and physician services in our data set.

PMID- 9630123
TI  - Reducing random variation in reported rates of pressure ulcer development.
AB  - OBJECTIVES: The authors evaluated methods of reporting on rates of pressure ulcer
      development in long-term care to identify approaches that lead to more stable
      estimates of actual performance. METHODS: Performance measures for facilities
      that adequately adjust for both random variation and casemix should be relatively
      stable from one time period to the next. The authors calculated facility rates of
      pressure ulcer development over eight consecutive time periods and correlated
      measures over time using different reporting methods including z-scores,
      combining rates from several time periods, and limiting analyses to large
      facilities. Results were compared with a Monte Carlo simulation. RESULTS:
      Observed facility rates of pressure ulcer development varied considerably over
      time. The average correlation coefficient across seven time comparisons for
      observed rates was 0.17. Reporting performance as a z-score or limiting the
      analyses to large facilities increased the correlation. Combining two time
      periods was effective only when used with one of these other approaches. The
      correlation coefficient based on a simulation using only large facilities was
      0.51. CONCLUSIONS: Random variation affects reported rates of pressure ulcer
      development. Using only large facilities and combining two time periods limits
      the effects of random variation and results in more stable estimates of
      performance. When describing performance, management must consider tradeoffs
      between having more accurate data, the frequency with which data are provided,
      and whether it is given to all providers.

PMID- 9630124
TI  - The effects of clinical pathways for renal transplant on patient outcomes and
      length of stay.
AB  - OBJECTIVES: Clinical pathways have been implemented nationwide but little is
      understood about their effects on efficiency of care and patient outcomes. The
      present study examined the effects of both development and implementation of two
      renal transplant pathways. METHODS: Cohorts of patients at a university hospital
      were compared before, during, and after the development and implementation of two
      renal transplant clinical pathways: isolated renal transplant from cadaveric
      donors (n = 170) or from living donors (n = 178). Clinical pathways for cadaveric
      and living related donor renal transplants were developed and implemented.
      Hospital length of stay and complications and infections after renal transplant
      were determined. RESULTS: Mean length of hospital stay decreased after
      development and implementation of the cadaveric donor pathway (11.8 days after
      implementation versus 17.5 days before development). Cadaveric kidney recipients
      also had statistically fewer complications and infections after both guideline
      development and guideline implementation (57.1% before, 24.5% during, 18.5%
      after), but the greatest effect occurred during development. All of these
      findings persisted after control for demographic and comorbid factors. There were
      no changes in hospital stay, complications, or infections in the patients who
      received kidneys from living donors. CONCLUSIONS: The development and use of a
      clinical pathway for cadaveric donor renal transplant patients was associated
      with a significant decline in length of stay, complications, and infections, but
      much of the effect was seen during development rather than during implementation,
      and a closely related pathway for living related donor patients had no effect.
      Further understanding of what factors predict an effective pathway and what
      elements (ie, development or implementation) have an effect should be undertaken.

PMID- 9630125
TI  - Long-term patterns of service use and cost among patients with both psychiatric
      and substance abuse disorders.
AB  - OBJECTIVES: This is a longitudinal study designed to determine: (1) if patients
      dually diagnosed with psychiatric and substance abuse disorders incur higher
      health care costs than other psychiatric patients and (2) if higher costs can be
      attributed to particular subgroups of the dually diagnosed or types of care.
      METHODS: Two cohorts of veterans treated in Veterans Affairs mental health
      programs at the start of fiscal year 1991 were followed for 6 years: one cohort
      of inpatients (n = 9,813) and the other of outpatients (n = 58,001). Data were
      analyzed on utilization of all types of Veterans Affairs health care. Repeated
      measures analysis of variance was used to examine cost differentials between
      dually diagnosed patients and other patients. RESULTS: Dually diagnosed
      outpatients incurred consistently higher health care costs than other psychiatric
      outpatients, attributable to higher rates of inpatient psychiatric and substance
      abuse care; however, this difference decreased with time. Costs were
      substantially higher in the inpatient cohort overall, but there were no
      differences in cost between dually diagnosed and other patients. CONCLUSIONS: In
      an atmosphere of cost cutting and moves toward outpatient care, the dually
      diagnosed may lose access to needed mental health services. Possibilities of
      developing more intensive outpatient services for these patients should be
      explored.

PMID- 9630126
TI  - Do treatment restrictions imposed by utilization management increase the
      likelihood of readmission for psychiatric patients?
AB  - OBJECTIVES: The use of utilization management as a cost-containment strategy has
      led to debate and controversy within the field of mental health. Little is
      currently known about how this cost-containment approach affects patient care or
      quality. The aim of this investigation was to determine whether treatment
      restrictions imposed on privately insured psychiatric patients by a utilization
      management program affected the likelihood of readmission. METHODS: The
      utilization management program included three review activities: preadmission
      certification, concurrent review, and case management. During a 5-year period
      (1989-1993), 3,073 inpatient reviews were performed on 2,443 privately insured
      psychiatric patients. Using logistic regression, restrictions imposed by
      utilization management on length-of-stay in relation to 60-day readmission rates
      were investigated. RESULTS: The most common diagnoses among the psychiatric
      patients whose care was reviewed were alcohol dependence (22.9%), recurrent
      depression (22.5%), and single-event depression (20.8%). On average, 22.4 days of
      inpatient psychiatric treatment was requested through the review procedures, and
      15.5 days of care were approved by the utilization management program. Of the
      2,443 patients reviewed, 7.9% had a readmission within 60 days of their initial
      admission. Patients whose length-of-stay was restricted by utilization management
      were more likely to be readmitted. For each day that the requested length-of-stay
      was reduced, the adjusted odds of readmission within 60 days increased by 3.1% (P
      = 0.004). CONCLUSIONS: The utilization management program restricted access to
      inpatient psychiatric care by limiting length of stay. Although this approach may
      promote cost containment, it also appears to increase the risk of early
      readmission. Continuing attention should be paid to investigating the effects on
      quality of utilization management programs aimed at containing mental health
      costs.

PMID- 9630127
TI  - How valid are medical records and patient questionnaires for physician profiling
      and health services research? A comparison with direct observation of patients
      visits.
AB  - OBJECTIVES: This study was designed to determine the optimal nonobservational
      method of measuring the delivery of outpatient medical services. METHODS: As part
      of a multimethod study of the content of primary care practice, research nurses
      directly observed consecutive patient visits to 138 practicing family physicians.
      Data on services delivered were collected using a direct observation checklist,
      medical record review, and patient exit questionnaires. For each medical service,
      the sensitivity, specificity, and Kappa statistic were calculated for medical
      record review and patient exit questionnaires compared with direct observation.
      Interrater reliability among eight research nurses was calculated using the Kappa
      statistic for a separate sample of videotaped visits and medical records.
      RESULTS: Visits by 4,454 patients were observed. Exit questionnaires were
      returned by 74% of patients. Research nurse interrater reliabilities were
      generally high. The specificity of both the medical record and the patient exit
      questionnaire was high for most services. The sensitivity of the medical record
      was low for measuring health habit counseling and moderate for physical
      examination, laboratory testing, and immunization. The patient exit questionnaire
      showed moderate to high sensitivity for health habit counseling and immunization
      and variable sensitivity for physical examination and laboratory services.
      CONCLUSIONS: The validity of the medical record and patient questionnaire for
      measuring delivery of different health services varied with the service. This
      report can be used to choose the optimal nonobservational method of measuring the
      delivery of specific ambulatory medical services for research and physician
      profiling and to interpret existing health services research studies using these
      common measures.

PMID- 9630128
TI  - Cross-cultural differences in the reporting of global functional capacity: an
      example in cataract patients.
AB  - OBJECTIVES: Patient-based health status measures have an important role to play
      in the assessment of health care outcomes. Among these measures, global
      assessments increasingly have been used, although the understanding of the
      performance of these indicators and the determinants of patients responses is
      underdeveloped. In this study, the performance of a single-item global indicator
      of visual function in cataract patients of four international settings was
      compared. METHODS: Visual acuity and ocular comorbidity was assessed by patients'
      ophthalmologist using Snellen-type charts in patients referred for a first
      cataract surgery in the United States, Manitoba (Canada), Denmark, and Barcelona
      (Spain). Patients also were interviewed by telephone and asked to report overall
      trouble with vision on a single-item indicator ("great deal," "moderate," "a
      little," "none") and to complete the Visual Functioning Index (VF-14), a scale of
      visual function ranging from 0 (worst function) to 100 (best level of function),
      along with other questions including the degree the patient was bothered by
      symptoms as measured by the Cataract Symptom Score (CSS). A total of 1,407
      patients completed the clinical examination and the preoperative interview.
      RESULTS: Distribution of overall trouble with vision varied across the sites,
      with the proportion of patients reporting a great deal of trouble ranging from
      21.7% to 37.9%. In all sites, patients reporting more trouble with vision tended
      to show a poorer age-adjusted and sex-adjusted visual acuity. The proportion of
      patients reporting great deal of trouble with vision was higher in the groups
      with worse visual acuity (P < 0.001). In multivariate analysis, after controlling
      for clinical and sociodemographic factors, the patients from Manitoba (OR = 0.32,
      95% CI = 0.20, 0.51) and those from Barcelona (OR = 0.33, 95% CI = 0.20, 0.56)
      were less likely to report a great deal of trouble with their vision (P < 0.01)
      than the Danish and US patients. No such differences were found among the US
      patients from three sites. CONCLUSIONS: There is international variation in the
      self-reporting of global vision-related functional capacity that is not explained
      by clinical or sociodemographic factors, which may be because of cultural
      differences. International comparisons of patient-based health outcomes should
      not rely only on single-item indicators until there is convincing evidence of
      their cross-cultural equivalence.

PMID- 9630129
TI  - Physician practice styles and patient outcomes: differences between family
      practice and general internal medicine.
AB  - OBJECTIVES: This study compared patient health status, patient satisfaction, and
      physician practice style between family practice and internal medicine. METHODS:
      New adult patients (n = 509) were prospectively and randomly assigned to family
      practice or internal medicine clinics at a university medical center and followed
      for 1 year of care. Practice styles were characterized by the Davis Observation
      Code. Self-reported health status (Medical Outcomes Study, Short Form-36) and
      patient satisfaction also were measured. RESULTS: There were no significantly
      different changes in self-reported health status or patient satisfaction between
      family practice and internal medicine physicians during the course of the study.
      Family practice initial encounters, however, were characterized by a style
      placing greater relative emphasis on health behavior and counseling, whereas
      internists used a more technical style. Improved health status scores after
      treatment were predicted by a practice style emphasis on counseling, whereas
      improvements in patient satisfaction scores were predicted by a style of care
      stressing patient activation. Although this is the first known randomized trial
      studying this issue, the conclusions are limited by a 38% loss of patients from
      enrollment to care and a loss of 18% at the 1-year follow-up evaluation.
      CONCLUSIONS: There were significant differences in practice styles between family
      physicians and internists; however, it was the physician's behavior, not
      specialty per se, that affected patient outcomes. A practice style emphasizing
      psychosocial aspects of care was predictive of improvements in patient health
      status, whereas a practice style emphasizing patient activation was predictive of
      improvements in patient satisfaction.

PMID- 9630130
TI  - Does practice make perfect? Examining the relationship between hospital surgical
      volume and outcomes for hip fracture patients in Quebec.
AB  - OBJECTIVES: Most tests of the practice-makes-perfect hypothesis have used cross
      sectional data, which reveal that patients receiving surgery in high-volume
      hospitals tend to experience better postsurgery outcomes. This study uses
      longitudinal data to explicitly examine whether any given hospital's patient
      outcomes change as its surgery volume varies with time. METHODS: Longitudinal
      data from all hospitals conducting hip fracture surgery in Quebec between 1990
      and 1993 were used to examine the relationship between surgery volume and
      outcomes. The longitudinal data allowed volume to be measured using the actual
      number of surgeries performed by the admitting hospital in the 12 months before a
      patient's surgery. Determinants of postsurgery length of stay were assessed using
      ordinary least squares regression, and the explanators of inpatient mortality
      were identified using logistic regression. The regressions included fixed effects
      (hospital-specific dummy variables) to control for systematic differences in
      outcomes across hospitals that persist with time. Therefore, the coefficient on
      hip fracture surgery volume in the regression models captured differences in
      outcomes that were attributable to changes in surgery volume within hospitals
      with time. RESULTS: The fixed effects were significant explanators of both
      postsurgery length of stay and inpatient mortality, indicating that there were
      significant differences in outcomes across hospitals that persisted with time. In
      regressions that excluded the fixed effects, the coefficient on surgery volume
      was significant. In contrast, the coefficient on surgery volume was insignificant
      when the fixed effects were included. CONCLUSIONS: Longitudinal data revealed
      that after controlling for differences in hospital outcomes that were fixed with
      time, hospitals performing more surgeries in one period than in another
      experienced no significant improvement in outcomes. These results do not support
      the "practice makes perfect" hypothesis. The volume-outcome relationship for hip
      fracture patients thus appears to reflect fixed differences in quality between
      high-volume and low-volume hospitals.

PMID- 9630131
TI  - Compliance of frail elderly with health services prescribed at discharge from an
      acute-care geriatric ward.
AB  - OBJECTIVES: A model of compliance by frail elderly with prescribed healthcare
      services was developed and tested. The discrepancy between primary care,
      geriatric and community health center (CLSC) services prescribed at discharge
      after comprehensive geriatric evaluation and treatment was measured, as were
      those services actually used during a 6-week interval (compliance). In this
      model, compliance was directly related to elders' intention to adhere to
      prescribed services, but this relationship was modified by organizational
      factors, reinforcing factors, and changes in health status during the observation
      period. Intention to adhere resulted from individual and reinforcing factors
      existing before discharge. METHODS: This model was tested on 211 patients
      discharged to community settings from an acute-care hospital geriatrics ward.
      Information was obtained through interviews with the patients or care givers and
      from hospital, outpatient, and local community health center charts. RESULTS: On
      average, patients used 56.9% of services prescribed; 13% of patients did not use
      any of the services prescribed for them, whereas 22% used all the services
      prescribed. Intention to adhere was influenced by patients' perception of the
      benefits of prescribed services and by their perception of the ease of access to
      transportation. Intention itself was not found to be an important determinant of
      overall compliance. Among organizational factors, having the ward staff make a
      follow-up appointment with the patients' family doctor and with the geriatric
      clinic before discharge and communication with the local community health center
      increased overall compliance. Moreover, patients who perceived they had access to
      transportation and to an accompanying person were more likely to comply.
      CONCLUSIONS: The results suggest that when discharging patients to the community,
      steps taken for them by the discharging healthcare providers will improve
      compliance.

PMID- 9630132
TI  - Fitting the distributions of length of stay by parametric models.
AB  - OBJECTIVES: The purpose of this study was to assess the adequacy of three widely
      used models--Lognormal, Weibull, and Gamma--for describing the distribution of
      length of stay. This is a fundamental step in the development of outliers
      resistant (robust) methods for the statistical analysis of this kind of data,
      where the main objective is to determine measures of average and total resource
      consumption of groups of patients. Current practice uses several types of
      trimming rules, many of which are based on the Lognormal model, although
      theoretical and experimental bases are still insufficient. METHODS: The three
      models were adjusted using robust procedures based on M-estimators to
      approximately 5 million stays grouped by Diagnosis-Related Groups (DRGs). The
      resulting 3,279 samples were collected in five European countries during 3 years.
      RESULTS: Most of the distributions observed could be fitted with one of these
      models. The descriptions provided by the Gamma and the Weibull models were
      similar, and the Gamma model could be omitted. The casemix description provided
      by the Log-normal-Weibull family was, for certain countries, significantly better
      than the one provided by the single Lognormal model. Often, for a given DRG and a
      given country, length of stay distributions could be described with the same
      model during several years. A given DRG, however, usually had to be described by
      means of different models for different countries. CONCLUSIONS: Practical and
      conceptual consequences of the results are discussed. They can be extended to the
      analyses of other consumption variables used in health services. Statistical
      procedures for casemix description, including current rules of trimming, should
      be improved by means of more flexible families of models.

PMID- 9630133
TI  - Profiling outcomes of ambulatory care: casemix affects perceived performance.
AB  - OBJECTIVES: The authors explored the role of casemix adjustment when profiling
      outcomes of ambulatory care. METHODS: The authors reviewed the medical records of
      656 patients with hypertension, diabetes, or chronic obstructive pulmonary
      disease (COPD) receiving care at one of three Department of Veterans Affairs
      medical centers. Outcomes included measures of physiological control for
      hypertension and diabetes, and of exacerbations for COPD. Predictors of poor
      outcomes, including physical examination findings, symptoms, and comorbidities,
      were identified and entered into regression models. Observed minus expected
      performance was described for each site, both before and after casemix
      adjustment. RESULTS: Risk-adjustment models were developed that were clinically
      plausible and had good performance properties. Differences existed among the
      three sites in the severity of the patients being cared for. For example, the
      percentage of patients expected to have poor blood pressure control were 35% at
      site 1, 37% at site 2, and 44% at site 3 (P < 0.01). Casemix-adjusted measures of
      performance were different from unadjusted measures. Sites that were outliers (P
      < 0.05) with one approach had observed performance no different from expected
      with another approach. CONCLUSIONS: Casemix adjustment models can be developed
      for outpatient medical conditions. Sites differ in the severity of patients they
      treat, and adjusting for these differences can alter judgments of site
      performance. Casemix adjustment is necessary when profiling outpatient medical
      conditions.

PMID- 9630134
TI  - Recruiting physicians for office-based research.
AB  - OBJECTIVES: Research conducted in community outpatient offices can provide
      insight into the common experiences of patients and physicians. However,
      recruiting physicians to participate in office-based research is challenging and
      few descriptions of methods that have been used to successfully recruit random
      samples of physicians are available. This article describes recruitment
      strategies utilized in a project that achieved high rates of participation from
      community-based primary care physicians and surgeons. METHODS: Recruitment
      methods included the use of advisory boards to identify potential barriers to
      participation, use of respected members of the medical community as recruiters,
      and obtaining endorsements from physician organizations and prominent members of
      the medical community. RESULTS: Overall, 81% of physicians contacted from a
      sample frame agreed to participate in the project. Participating physicians most
      frequently reported that they participated because the project could provide them
      with feedback about their interviewing style. CONCLUSIONS: The recruitment
      methods described here can be generalized to other types of investigations.

PMID- 9630135
TI  - Sudden infant death syndrome rates subsequent to the American Academy of
      Pediatrics supine sleep position.
AB  - OBJECTIVES: In April 1992, the American Academy of Pediatrics (AAP) recommended
      that healthy infants be positioned for sleep on their side or back to reduce the
      risk of Sudden Infant Death Syndrome (SIDS). The authors hypothesized three
      different forms of the intervention to examine the impact of the recommendation
      according to theory such as technology diffusion. Seasonality was included in the
      models to control its effect when testing. METHODS: Box and Tiao time-series
      intervention methodology was used to examine the effect of the AAP recommendation
      on SIDS rates. Sudden Infant Death Syndrome mortality data from Philadelphia and
      Chicago were examined separately for white and nonwhite populations over 32
      quarters. RESULTS: Overall SIDS rates dropped significantly according to an
      abrupt effect from the intervention. However, the effect appeared to be gradually
      declining in Philadelphia but permanent in Chicago. In Philadelphia, a decline of
      62.3% was estimated in whites in the first quarter after the intervention but
      decreased to only 5% in the last quarter of 1994. A decline of 35.8% was
      estimated in nonwhites in the first quarter after the intervention but decreased
      to only 9.4% in the last quarter of 1994. An abrupt and permanent decrease of
      26.7% and 16.5% was found in Chicago for whites and nonwhites, respectively.
      CONCLUSIONS: Evidence of an abrupt adoption of the recommendation can be
      explained by the authority innovation decision made by the AAP. Some evidence was
      found that the effect is temporary, perhaps because physicians are reversing
      earlier decisions. The demonstrated methodology provides a powerful way to test
      naturally occurring interventions from quasiexperimental designs to test the
      impact of policy guidelines.

PMID- 9630136
TI  - Influenza vaccinations of Washington state Medicare beneficiaries seen by
      physiatrists in the outpatient setting in 1994.
AB  - OBJECTIVE: To compare influenza vaccination billing rates for patients seen by
      physiatrists with those of four other specialties: neurology, rheumatology,
      family practice, and internal medicine. DESIGN: Retrospective cohort analysis
      using Medicare billing data. PATIENTS: 234,164 Medicare outpatients seen in
      Washington state between September 1 and December 31, 1994. RESULTS: Based on
      Medicare's billing data, only 6 of 99 physiatrists ordered vaccinations, and they
      immunized only 159 (6%) of the patients seen. An additional 1,109 (42%) patients
      seen by physiatrists were vaccinated by other physicians. Physiatric patients
      were less likely to have been vaccinated than those seen by internists, family
      practitioners, or rheumatologists (p < .002), but equally likely as those seen by
      neurologists (p = .07). A significantly smaller percentage of physiatrists
      ordered vaccinations than all other specialties (p < .04). Utilizing pre-existing
      survey data, the misclassification rate (those immunized but not billed) was
      estimated at 22% of our original cohort. Thus, approximately 800 patients, one
      third of those seeing physiatrists, may not have been immunized. We estimated the
      increase in hospitalization costs to be $117 per nonvaccinated patient (total
      >$90,000). CONCLUSIONS: Missed opportunities for vaccination by physiatrists
      appear to be more frequent than in other specialties and have potentially large
      health and economic costs.

PMID- 9630137
TI  - Chronic pain in a community-based sample of men with spinal cord injury:
      prevalence, severity, and relationship with impairment, disability, handicap, and
      subjective well-being.
AB  - OBJECTIVE: To assess the prevalence, severity, and correlates of chronic pain in
      a community-based sample of men with spinal cord injury (SCI). DESIGN: Survey.
      SETTING: Community. PARTICIPANTS: Seventy-seven men with SCI randomly selected
      from a sampling frame solicited from the community. METHOD: Participants
      completed standardized questionnaires assessing many areas of life, were
      interviewed in their homes, and underwent a physical examination at a hospital.
      There they were interviewed by an anesthesiologist regarding chronic pain, and a
      nurse administered objective pain measures. RESULTS: Seventy-five percent of the
      men reported chronic pain. Chronic pain was associated with more depressive
      symptoms, more perceived stress, and poorer self-assessed health. Greater
      intensity of pain was related to less paralytic impairment, violent etiology, and
      more perceived stress. Area of the body affected by pain was related to
      independence and mobility. CONCLUSIONS: Because of the high prevalence of chronic
      pain in the population with SCI and its relation to disability, handicap, and
      quality of life, health care providers need to give this issue the same priority
      given to other SCI health issues. Analysis of individual pain components provides
      better information than assessing overall pain. It is futile to treat SCI pain
      without giving full attention to subjective factors.

PMID- 9630138
TI  - Employment after spinal cord injury: differences related to geographic region,
      gender, and race.
AB  - OBJECTIVE: To compare employment outcomes after spinal cord injury (SCI) as a
      function of several important participant characteristics. DESIGN: Field study
      survey of the employment history of two large samples of people with SCI.
      Outcomes were compared as a function of multiple participant characteristics.
      SETTING: A large rehabilitation hospital in the Southeast, with the collaboration
      of two Midwestern hospitals. PARTICIPANTS: One thousand thirty-two individuals
      with SCI, 597 from the Southeast and 435 from the Midwest. MAIN OUTCOME MEASURES:
      The Life Situation Questionnaire-revised (LSQ-R), a self-report measure, was used
      to identify biographic status and to document employment history. RESULTS: On the
      average, currently employed participants were Caucasian, were younger when
      injured, had paraplegia, and had completed more years of education. Geographic
      differences in employment rates disappeared when controlled for multiple factors,
      including years of education. However, even after controlling for years of
      education, Caucasian participants were 2.8 times more likely than minority
      participants to be working at the time of the study. CONCLUSIONS: Rehabilitation
      professionals need to find creative means to identify and neutralize barriers to
      employment among individuals from minority groups and to identify meaningful
      avocations for individuals who are injured when they are near retirement.

PMID- 9630139
TI  - Semen quality in spinal cord injured men: does it progressively decline
      postinjury?
AB  - OBJECTIVE: To determine if semen quality of men with spinal cord injury (SCI)
      undergoes a progressive decline as a function of years postinjury. DESIGN: A
      retrospective analysis of cross-sectional data. SETTING: University-based
      research center. SUBJECTS: Semen quality was examined in 638 specimens from 125
      men with SCI. INTERVENTION: Penile vibratory stimulation, electroejaculation, and
      masturbation were used as semen retrieval methods. Routine semen analysis was
      performed to evaluate semen quality. MAIN OUTCOME MEASURES: Sperm concentration,
      total sperm count, and percent sperm motility were examined at 2-year intervals
      from men whose injuries had occurred 6 weeks to 26 years earlier. RESULTS: No
      difference in any semen parameter was found as a function of time postinjury.
      CONCLUSIONS: Semen quality in men with SCI does not progressively decline after
      the SCI. Men with SCI who are considering biologic fatherhood should be advised
      that the number of years after injury need not be a determinant in deciding when
      to start a family.

PMID- 9630140
TI  - Executive functioning and predictors of falls in the rehabilitation setting.
AB  - OBJECTIVE: To examine the incremental utility of executive function tests in the
      prediction of inpatient falls. DESIGN: Evaluation of neuropsychologic and medical
      risk factors for fall was completed at admission. Inpatient falls were tabulated
      following discharge. SETTING: A freestanding, urban rehabilitation hospital.
      PATIENTS: Ninety consecutive admissions to traumatic brain injury, orthopedic,
      and spinal cord injury wards. Age of the participants ranged from 17 to 73 years
      old. MAIN OUTCOME MEASURE: Incident reports of inpatient falls. RESULTS: Standard
      multiple regression analyses indicated that measures of executive functioning
      sensitive to self-monitoring accounted for unique variance in falls beyond that
      explained by age and functional motor ability as assessed by the Functional
      Independence Measure. Visuospatial functioning, although not directly related to
      falls, was a significant predictor in combination with measures of executive
      functioning. Together, these variables accounted for 30.3% of the variance in
      inpatient falls (multiple r = .55; p < .001). CONCLUSION: The findings suggest
      that the influence of motor and sensory impairments on falls are moderated, in
      part, by executive functioning. Patients with intact executive functioning are
      less likely to act in ways that could result in a fall; thus, aggressive fall
      prevention measures may be unnecessary. In contrast, executive dysfunction may
      signal the need for intervention, even among patients whose profiles are
      unremarkable with regard to traditional risk factors for fall.

PMID- 9630141
TI  - Endplate spike morphology: a clinical and simulation study.
AB  - OBJECTIVE: To describe the various morphologic appearances of endplate spikes,
      define the theoretical volume conduction basis of these waveforms' morphologies,
      and simulate "atypical" endplate spike waveforms documented by other
      investigators. DESIGN: Endplate spikes were recorded from the biceps brachii in
      healthy individuals using a monopolar needle electrode. The morphologies of these
      waveforms were compared with those obtained from a computer simulation.
      Previously documented endplate waveforms were simulated using two fundamental
      types of biphasic initially negative and positive waveform morphologies. SETTING:
      University clinic outpatient electrodiagnostic medicine facility. SUBJECTS: Five
      subjects without history or physical evidence of neuromuscular disease. MAIN
      OUTCOME MEASURES: Endplate potential morphologies were assessed with respect to
      overall waveform shape and number of phases. Computer-generated waveforms for
      individual endplate spike waveforms were qualitatively compared with those
      recorded from the subjects. RESULTS: Three fundamental waveforms were documented
      to arise from the endplate regions of all subjects and were successfully
      simulated: (1) biphasic initially negative potential from the endplate itself and
      up to 0.2mm from the endplate, (2) triphasic initially positive potential from
      within 0.2mm of the endplate up to 0.5mm from the musculotendinous junction, and
      (3) biphasic initially positive potential from the last 0.4mm of the fiber or
      from impulse blocking. Two biphasic endplate spike waveforms could be summated to
      generate all other endplate waveforms described in previously documented
      literature. CONCLUSION: The combination of clinical and simulation studies
      suggests that endplate spike potentials can have quite varied morphologies.
      Triphasic initially positive and biphasic initially positive endplate spikes may
      be mistaken for fibrillation potentials and positive sharp waves, respectively.
      The triphasic waveforms most likely arise from an action potential propagating
      past the recording electrode adjacent to the endplate, while the biphasic
      initially positive potential is simulated to arise from the needle electrode
      blocking action potential propagation.

PMID- 9630142
TI  - Functional electrical stimulation effect on skeletal muscle blood flow measured
      with H2(15)O positron emission tomography.
AB  - OBJECTIVE: To test the hypothesis that the limitation in muscle power development
      with functional electrical stimulation (FES) results from an insufficient
      increase in muscle blood flow (MBF) in response to activity. SUBJECTS AND
      METHODS: Five subjects with neurologically complete spinal cord injury (SCI) were
      tested to measure the MBF response to FES-induced knee extension. The MBF
      response to voluntary knee extension was measured in five age-matched, able
      bodied controls. MBF was measured with positron emission tomography (PET) using
      H2(15)O as a tracer. Three scans were performed with muscle at rest (baseline),
      immediately after 16min of FES-induced or voluntary knee extension (activity),
      and 20min after the second scan (recovery). RESULTS: In SCI subjects, mean +/-SE
      MBF (mL/100g/min) values were: baseline = 1.85 +/- .48; post-FES = 31.9 +/- 5.65
      (p = .0058 vs baseline); recovery = 6.06 +/- 1.52 (p = .0027 vs baseline). In
      able-bodied controls, mean +/-SE MBF values were: baseline = 8.52 +/- 3.24, post
      voluntary exercise = 12.62 +/- 3.03 (p = .023 vs post-FES in SCI subjects);
      recovery = 10.7 +/- 6.01. CONCLUSIONS: MBF does not appear to be the limiting
      factor in muscle power generation with FES. The greater increase in MBF observed
      with FES in SCI subjects when compared with able-bodied subjects performing a
      similar task (unloaded knee extension against gravity) may relate to abnormal
      metabolism in FES-stimulated muscle.

PMID- 9630143
TI  - Goniometric assessment of shoulder range of motion: comparison of testing in
      supine and sitting positions.
AB  - OBJECTIVE: To examine intrarater reliability in measurements of active range of
      motion and passive range of motion of shoulder flexion and abduction when motions
      are assessed in sitting, as compared with supine. DESIGN: Thirty adult subjects
      were measured eight times, in random order, for each of the two shoulder motions:
      two passive and two active measurements while sitting, and two passive and two
      active measurements while supine. Data were analyzed to determine intraclass
      correlation coefficients (ICCs) and paired t values between trials 1 and 2 for
      measurements in the same position, and between sitting and supine trials for each
      type of measurement. SETTINGS: Rehabilitation facility and university. STUDY
      POPULATION: Volunteer sample: 11 rehabilitation inpatients; 19 university
      students. RESULTS: ICCs between trials 1 and 2 on comparable measurements in the
      same position indicated high intrarater reliability for active and passive
      measurements, regardless of testing position. ICCs between comparable
      measurements in the two testing positions indicated only a moderate level of
      agreement. Paired t tests between comparable readings taken in sitting versus
      supine revealed no significant differences for flexion, but significantly higher
      measurements of abduction when testing in the supine position. CONCLUSIONS:
      Measurements in sitting or supine yield similarly high intrarater reliability.
      Lowered reliability between measurements taken in different positions indicates
      that test position should be routinely recorded, and repeated clinical measures
      of individual subjects should be administered in a consistent position.

PMID- 9630144
TI  - Aerobic circuit exercise training: effect on adolescents with well-controlled
      insulin-dependent diabetes mellitus.
AB  - OBJECTIVES: To test the safety and effects of exercise conditioning on
      cardiorespiratory fitness, body composition, muscle strength, glucose regulation,
      and lipid/cholesterol levels. SUBJECTS: Ten male adolescents with insulin
      dependent diabetes mellitus (IDDM) and 10 adolescent nondiabetic (ND) subjects.
      DESIGN: Pretest, posttest intervention trial with control group. SETTING:
      University-based human performance laboratory. INTERVENTION: Mixed endurance and
      calisthenic/strength activities performed at a rapid pace three times weekly for
      12 weeks. RESULTS: Only one subject with IDDM experienced hypoglycemia after a
      single exercise session. Both subject groups improved their cardiorespiratory
      endurance (p < .05). Lean body mass of IDDM subjects increased by 3.5% (p < .05).
      Subjects with and without IDDM lowered their percent body fat (p < .05 and .001,
      respectively). Strength improvement of IDDM subjects ranged from 13.7% (p < .001)
      to 44.4% (p < .01), depending upon the maneuver. Fasting blood plasma glucose for
      all subjects was unchanged by training, but glycosylated hemoglobin A1c of IDDM
      subjects was reduced by .96 percentage point (p < .05). Reductions of HbA1c
      benefitted subjects exhibiting poor preconditioning glycemic control. Low-density
      lipoprotein cholesterol was decreased in subjects with IDDM (p < .05), but not
      total cholesterol or triglycerides. CONCLUSION: Adolescents with IDDM undergoing
      aerobic circuit training improve their cardiorespiratory endurance, muscle
      strength, lipid profile, and glucose regulation. Aerobic circuit training is safe
      for properly trained and monitored adolescent diabetics.

PMID- 9630146
TI  - Three-dimensional kinematics and trunk muscle myoelectric activity in the young
      lumbar spine: a database.
AB  - OBJECTIVE: To document the three-dimensional (3D) kinematics of the lumbar spine
      and the myoelectric activity of trunk muscles throughout the range of motion in
      selected tasks performed by healthy subjects. DESIGN: A survey of a single
      population. SETTING: A research laboratory in a university setting. PARTICIPANTS:
      Twenty-four men and women, university-age, with no history of chronic lower back
      pain volunteered for this study. INTERVENTIONS: The selected tasks consisted of
      lateral bend and axial twists to the right and left plus four different flexion
      extension tasks that varied a hand-held weight (10kg and 0kg), and flexion
      extension velocity (free-paced and 20 degrees/sec). MAIN OUTCOME MEASURE: 3D
      lumbar spine kinematics and normalized, linear enveloped electromyogram (EMG) of
      trunk muscles. RESULTS: The motion time histories were illustrated graphically.
      Consistent spinal kinematics and EMG activation patterns during each task across
      subjects were seen. Peak displacement values between tasks, using one-way
      analysis of variance, showed no significant difference. CONCLUSION: A database of
      healthy spine kinematics and normalized linear enveloped trunk muscle activation
      patterns were developed for future comparison of elderly and pathological
      subjects.

PMID- 9630145
TI  - The fiber-type-specific effect of inactivity and intermittent weight-bearing on
      the gastrocnemius muscle of 30-month-old rats.
AB  - OBJECTIVE: To characterize single skeletal muscle fiber contractile properties
      from the gastrocnemius muscle that occur during inactivity and intermittent
      weight-bearing in 30-month-old animals. DESIGN: Randomized control trial.
      SETTING: A controlled laboratory environment. SUBJECTS: Eighteen 30-month-old
      male Fisher 344 Brown Norway F1 Hybrid rats were randomly assigned to control
      (C), hindlimb unweighted (HU), and hindlimb unweighted with intermittent weight
      bearing (HU-X) groups. INTERVENTIONS: The HU and HU-X rats were suspended for 7
      days. The HU-X animals were unsuspended for four 15-minute bouts of weight
      bearing. MAIN OUTCOME MEASURES: Single skeletal muscle fiber contractile
      properties (diameter, peak active force [P0], peak specific tension [P0/CSA], and
      maximal shortening velocity [V0] by fiber type) were determined from the deep
      portion of the lateral head of the gastrocnemius muscle (RG). RESULTS: In
      comparison to C animals, the ratio of gastrocnemius weight to body weight
      decreased by 18% and 14% following HU and HU-X, respectively. Diameter and P0 of
      type I fibers from the RG were reduced after HU. Attenuation of the decline in
      diameter and P0 was observed in type I fibers from the RG with HU-X. P0 was
      reduced in type IIa fibers and type I-IIa fibers with HU. Attenuation of the
      decline in P0 by intermittent weight-bearing in type IIa fibers and type I-IIa
      fibers did not occur. CONCLUSIONS: Inactivity altered the contractile properties
      of single skeletal muscle fibers from the gastrocnemius muscle of 30-month-old
      animals. The inactivity-induced alterations were present in the three fiber
      types. Therapeutic intervention of weight-bearing attenuated the inactivity
      induced changes in the type I fibers from the gastrocnemius, but not the other
      fiber types.

PMID- 9630147
TI  - Nursing home rehabilitation after acute rehabilitation: predictors and outcomes.
AB  - OBJECTIVE: To determine the predictive factors and functional outcomes of
      patients who were discharged from an acute rehabilitation unit to a nursing home
      care unit (NHCU) at a Veterans Affairs (VA) hospital. DESIGN: Cohort descriptive
      study. SETTING: An academically affiliated urban VA Medical Center. PATIENTS: All
      patients (n = 81, median age 68 years) admitted to a VA rehabilitation unit over
      a 1-year period. OUTCOME MEASURES: Discharge locations, predictors for NHCU
      transfer, and functional status as determined by Functional Independence Measure
      (FIM) scores. RESULTS: Patients discharged to the NHCU (17%) were compared with
      those discharged to the community (80%). Multiple logistic regression analysis
      showed that acute rehabilitation length of stay (LOS), admission, and discharge
      FIM scores were the only independent variables that predicted discharge to the VA
      NHCU. Although overall FIM gains in both groups during acute rehabilitation were
      similar, the NHCU group had significantly lower admission FIM scores and lower
      LOS efficiency because of longer acute rehabilitation LOS. Postacute NHCU
      rehabilitation resulted in significant gains in FIM scores at a slower rate.
      Sixty-four percent of these nursing home patients eventually returned to the
      community. CONCLUSION: Nursing home rehabilitation can result in favorable
      functional and community outcomes for selected patients.

PMID- 9630148
TI  - Personal assistance for people with physical disabilities: consumer-direction and
      satisfaction with services.
AB  - OBJECTIVE: To determine whether people who receive consumer-directed personal
      assistance services (PAS) are more satisfied with the services they receive than
      those receiving PAS that are not consumer-directed. DESIGN: A quasi-experimental
      survey comparison of long-term outcomes among people receiving consumer-directed
      PAS in Virginia and persons on the waiting list to receive those services.
      Surveys were conducted by mail and telephone. SETTING: The general community in
      Virginia. PARTICIPANTS: Ninety-two Virginia residents with physical disabilities
      living in the community. Sixty individuals were receiving consumer-directed PAS,
      and 32 were on the waiting list for consumer-directed PAS and were receiving paid
      personal assistance that was not consumer-directed. MAIN OUTCOMES MEASURES: The
      Personal Assistance Satisfaction Index (PASI); chi2 and t tests were conducted.
      RESULTS: People receiving consumer-directed PAS scored significantly higher on
      the PASI than the waiting-list control group and were consistently more likely to
      report high levels of satisfaction on the majority of individual PASI items.
      CONCLUSION: Consumer-directed PAS are associated with high levels of satisfaction
      relative to PAS that are not consumer-directed. Individual PASI items related to
      control over PAS and flexibility of services showed the greatest differences in
      satisfaction.

PMID- 9630149
TI  - Traumatic brain injury: efficacy of multidisciplinary rehabilitation.
AB  - OBJECTIVE: To establish efficacy of a coordinated multidisciplinary
      rehabilitation service for severe head injury, provided at Hunters Moor Regional
      Rehabilitation Centre. DESIGN: A quasi-experimental design to compare treatment
      effects between two groups. The first group received a coordinated,
      multidisciplinary regional rehabilitation service; the other, a single discipline
      approach provided by local, district hospitals. Follow-up was for 2 years
      postinjury. PATIENTS OR OTHER PARTICIPANTS: Fifty-six consecutive severe head
      injury admissions, with an identified main caregiver, referred for rehabilitation
      within 4 weeks of their injury. MAIN OUTCOME MEASURES: The Barthel index, the
      Functional Independence Measure (FIM), and the Newcastle Independence Assessment
      Form (NIAF), a newly developed, real-life, comprehensive measure. In addition,
      caregivers completed the General Health Questionnaire. RESULTS: The group that
      received coordinated multidisciplinary rehabilitation not only demonstrated
      significant gains throughout the study period but also maintained treatment
      effect after input ended. Furthermore, caregivers of this group had significantly
      reduced levels of distress. The comparison group, despite initial lower injury
      severity and shorter hospital stay, did not demonstrate equivalent gains or any
      posttreatment effect. CONCLUSIONS: The results show the efficacy of a
      comprehensive, specialist multidisciplinary regional service. There are
      significant implications for service provision for people with severe traumatic
      head injury.

PMID- 9630150
TI  - Outcome assessment after milieu-oriented rehabilitation: new considerations.
AB  - OBJECTIVE: This study incorporated level of functional impairment ratings at
      program admission into rehabilitation outcome (return to work/school) at the time
      of program discharge. HYPOTHESES: (1) Patients and families with better working
      alliance ratings will show better adjusted outcome; (2) patients seeking
      compensation will have poorer outcome than those not seeking compensation or
      receiving benefits; (3) speed of information processing and memory will relate to
      the level of adjusted outcome. DESIGN: Consecutive neurorehabilitation admissions
      from March 1992 to May 1996. SETTING: Outpatient milieu-based interdisciplinary
      day treatment program. SUBJECTS: Sixty-four patients with heterogeneous brain
      injury etiologies. MAIN OUTCOME MEASURES: Adjusted outcome, defined as level of
      discharge productivity adjusted by staff ratings of functional severity of
      impairment at program admission; work readiness and work eagerness, based on
      average staff ratings. RESULTS: At discharge, 89.5% of patients showed fair or
      good adjusted outcome; 62% were gainfully employed/full-time students; 15.6%
      resumed preinjury status. Better working alliance predicted better adjusted
      outcome. Patients seeking compensation showed significantly lower work eagerness
      ratings. Poorer outcome was associated with better neuropsychological status.
      CONCLUSIONS: Efficacy of neurorehabilitation was demonstrated for patients with
      better working alliance who were not seeking compensation. Adjusted outcome
      demonstrated greater sensitivity and utility by incorporating the variable of
      functional severity of impairment at program admission. Inclusion of "process"
      variables addressing working alliance, motivation, and capacity to work provide
      important contributions to understanding rehabilitation outcome.

PMID- 9630151
TI  - Bolus aggregation in the oropharynx does not depend on gravity.
AB  - OBJECTIVE: To determine whether bolus aggregation in the oropharynx (before
      swallowing) depends on gravity. DESIGN: Before-during trial, with subjects
      serving as their own controls. SETTING: Hospital radiology suite. PARTICIPANTS:
      Five asymptomatic adult volunteers. INTERVENTIONS: Videofluorography was
      performed while subjects ate soft and hard foods containing barium, first seated
      upright and then kneeling face down (quadruped position). MAIN OUTCOME MEASURES:
      Duration of food processing in the oral cavity, bolus aggregation in the
      valleculae, and pharyngeal swallow. RESULTS: Transport of chewed solid food from
      the oral cavity to the oropharynx (stage II transport) typically started several
      seconds before onset of swallow, regardless of head position or initial food
      consistency. Bolus aggregation in the valleculae (between the epiglottis and the
      tongue) began an average of 1.7 +/- 2.5sec before the onset of the pharyngeal
      swallow (p < .001). Stage II transport was driven by tongue-palate contact.
      CONCLUSIONS: Transport of chewed solid food from the oral cavity to the pharynx
      is driven actively by tongue-palate contact and does not depend on gravity. A
      bolus may accumulate in the valleculae for several seconds before the swallow.

PMID- 9630152
TI  - Intractable hiccups during stroke rehabilitation.
AB  - OBJECTIVE: To study the frequency of intractable hiccups during stroke
      rehabilitation and the impact on rehabilitation management. DESIGN: Case series,
      retrospective chart review. SETTING: Inpatient stroke rehabilitation floor within
      a tertiary care teaching hospital. PATIENTS: Three patients admitted for stroke
      rehabilitation with hiccups of at least 48 hours out of 270 consecutive cases.
      INTERVENTIONS: None. MAIN OUTCOME MEASURE: Response to pharmacologic treatment.
      RESULTS: All three subjects had pontine infarcts and required gastrostomy tube
      feedings and lengthy rehabilitation stays. Subjects suffered from significant
      complications including aspiration pneumonia, respiratory arrest, and nutritional
      depletion. Chlorpromazine treatment was terminated in all three subjects because
      of sedation that interfered with therapies. Treatment with carbamazepine was
      successful in only one patient; in the other two subjects, their hiccups were
      controlled with haloperidol or baclofen. All subjects were ultimately managed
      with a single agent. CONCLUSIONS: Pharmacologic interventions for intractable
      hiccups must be tailored to the unique circumstances of the stroke rehabilitation
      patient. Intractable hiccups can be associated with potentially fatal
      consequences, and safe management may require an inpatient rehabilitation setting
      and multidisciplinary team approach to optimize the feeding management of this
      challenging population.

PMID- 9630153
TI  - Lumbar spinal stenosis: a review of current concepts in evaluation, management,
      and outcome measurements.
AB  - The purpose of this review is to present current information from the literature
      regarding the pathoanatomy, clinical presentation, differential diagnosis,
      treatment, and outcome assessment methods for patients with lumbar spinal
      stenosis. Lumbar spinal stenosis is a frequently encountered condition,
      particularly in the elderly. Treatment requires an accurate diagnosis, but
      differential diagnosis of lumbar stenosis can be difficult. The literature to
      date has focused primarily on surgical treatment. The long-term efficacy of
      surgery has been questioned, and surgical procedures are associated with
      increased costs and risks of morbidity in an elderly population. A trial of
      conservative care is recommended in most cases, but there are presently no
      randomized controlled studies in the literature comparing surgical versus
      conservative management, or evaluating the effectiveness of any specific
      conservative treatment approach. The existing literature has further been
      criticized for having poorly defined outcome measures. The assessment of
      treatment outcomes should be multifactorial, including measures of pathoanatomy
      and impairments, as well as patient-centered measures such as level of
      disability, patient expectations, and satisfaction. The present level of
      understanding of lumbar spinal stenosis is deficient in many areas, including
      differential diagnosis, treatment, and outcome assessment. Future research should
      address these deficits to improve the management of patients with this condition.

PMID- 9630154
TI  - Diagnosis and rehabilitation strategies for patients with hysterical hemiparesis:
      a report of four cases.
AB  - Conversion disorder is a psychological disturbance that produces subconscious
      alterations in sensorimotor function. Hysterical hemiparesis is a relatively
      rare, and difficult to diagnose, form of conversion disorder presenting as
      unilateral motor weakness with or without sensory deficits. We report four
      patients who required inpatient rehabilitation for hysterical hemiparesis, a
      diagnosis for which there is little information regarding rehabilitation
      management. In all cases, an extensive acute care evaluation including multiple
      imaging studies failed to identify a new neurologic lesion. All patients had
      rapid functional improvement using functional and behavioral therapies and
      extensive psychosocial support (mean length of stay of 11 days; mean Functional
      Independence Measure [FIM] gain of 22; mean discharge FIM of 112), consistent
      with other published reports of rehabilitation of conversion disorder. Evaluation
      of these cases reveals consistencies regarding presentation, psychosocial
      history, and rehabilitation course that can aid clinicians in making the
      diagnosis. Rehabilitation strategies for hysterical hemiparesis are reviewed.

PMID- 9630155
TI  - Treatment of detrusor sphincter dyssynergia by transperineal injection of
      botulinum toxin.
AB  - Detrusor-sphincter dyssynergia is an involuntary contraction of the external
      urethral sphincter during the detrusor contraction. It causes voiding dysfunction
      and can lead to urologic complications such as hydroureteronephrosis and renal
      failure. Patients with spinal cord injuries are particularly vulnerable.
      Botulinum toxin has been used via cystoscopy to decrease the activity of the
      external urethral sphincter. This report describes the treatment of 5 tetraplegic
      patients by single transperineal injections of botulinum toxin for detrusor
      sphincter dyssynergia, proved by a urodynamic study with electromyography. A
      total of 15 injections was given, resulting in improved bladder function in all
      patients. Urodynamic assessment after treatment showed an increase of the
      functional detrusor capacity and a decrease of the maximal detrusor pressure
      during voiding. These results confirm the consideration of botulinum toxin as a
      treatment for detrusor sphincter dyssynergia. A single transperineal injection is
      a valuable, less invasive treatment using a cystoscopic technique.

PMID- 9630157
TI  - Rear-end auto collisions.

PMID- 9630156
TI  - Effective serial measurement of cognitive orientation in rehabilitation: the
      Orientation Log.
AB  - OBJECTIVE: To introduce a brief quantitative measure of cognitive orientation (to
      place, time, and situation) developed for daily use at bedside with
      rehabilitation inpatients. The Orientation Log (O-Log) is a 10-item scale that
      allows for partial credit based on responsiveness to logical, multiple-choice, or
      phonemic cueing. It is formatted for rapid visual analysis of orientation trends
      that can be used to evaluate pharmacologic and cognitive-behavioral
      interventions. DESIGN: Descriptive study of the O-Log's reliability (interrater
      and internal consistency). SETTING: Inpatient rehabilitation center affiliated
      with a large university medical school. PATIENTS: Fifteen neurorehabilitation
      inpatients. RESULTS: For individual items, Spearman rho interrater reliability
      coefficients ranged from .851 to 1.00. The interrater reliability of the total
      score was .993. O-Log internal consistency (coefficient alpha) was .922.
      CONCLUSIONS: The O-Log is a reliable and easily administered scale that promises
      to be a useful tool in monitoring cognitive recovery during rehabilitation.

PMID- 9630158
TI  - Rear-end auto collisions.

PMID- 9630159
TI  - Cytokine and chemokine production in HSV-1 latently infected trigeminal ganglion
      cell cultures: effects of hyperthermic stress.
AB  - The establishment of a primary trigeminal ganglion (TG) cell culture latently
      infected with herpes simplex virus type 1 (HSV-1) has been useful in studying
      stress-induced reactivation of the latent virus. However, the immune profile of
      this culture system prior to and after stress has never been established. In the
      present manuscript, cytokine and chemokine production were measured in primary
      cultures of TG cells obtained from uninfected and HSV-1 latently infected mice.
      Supernates from TG cell cultures contained detectable interleukin (IL)-6 but not
      IL-1beta, IL-2, IL-10, interferon (IFN)-gamma or tumor necrosis factor (TNF)
      alpha as determined by ELISA. The basal level of IL-6 in uninfected TG cell
      cultures was 20.5 +/- 2.3 ng/ml, whereas latently infected TG cells produced
      significantly less IL-6 (12.1 +/- 1.9 ng/ml). Supernates from TG cell cultures
      also contained detectable levels of C-10, MCP-1 and eotaxin but little to no MIP
      1alpha, MIP-1beta, or MIP-2. While there were no differences in the basal level
      of MCP-1 and eotaxin in TG cell cultures from HSV-1-infected and uninfected mice,
      C10 levels were significantly higher in TG cultures originating from infected
      mice compared to uninfected ones (5.86 +/- 0.61 ng/ml compared to 1.18 +/- 0.16
      ng/ml). Hyperthermic stress (43 degrees C, 180 min), which induces reactivation
      of latent HSV-1 from TG cell cultures, significantly reduced IL-6 and C-10 levels
      from both uninfected and latently infected TG cell cultures. However, there was
      no correlation between cytokine/chemokine levels and HSV-1 reactivation.
      Immunofluorescent studies showed TG cell cultures contained 10% MAC-3+ staining
      cells (macrophage specific) but no dendritic cells. By comparison, cells from
      freshly isolated TG contained 6% positive dendritic cells but < 1% MAC-3 + cells.
      Both in vivo and in vitro TG consisted of a low percentage of CD3+ and CD8+
      cells. Hyperthermic stress (43 degrees C for 3 h) eliminated the lymphocyte
      population as determined by RT-PCR. Whereas no spontaneous reactivation has been
      reported in mice, spontaneous reactivation occurred in 4.5% (10/220) of TG cell
      cultures surveyed over a 20 day period. Collectively, the dichotomy between HSV-1
      replication and reactivation comparing the in vitro and in vivo HSV-1 latency
      models may reside, in part, to the differences in the levels of cytokines,
      chemokines and immune cell populations within the microenvironment of the in
      vitro and in vivo TG.

PMID- 9630160
TI  - Glucocorticoids increase IL-10 expression in multiple sclerosis patients with
      acute relapse.
AB  - High doses of glucocorticoids (GCs) are widely employed to treat acute attacks in
      relapsing-remitting multiple sclerosis (MS) patients. Their beneficial effects
      are partially due to their capacity to regulate the cytokine network. In the
      present work, we have examined the effect of GCs on the production of the
      immunosuppressor cytokine IL-10. Blood samples from MS patients suffering an
      acute relapse were obtained immediately before initiating therapy and after
      receiving a daily dose of 1 g intravenous methylprednisolone (MP) for four days.
      Levels of IL-10 mRNA in PBMC were semiquantified by RT-PCR, whereas protein
      concentration in serum and in cell culture supernatant was measured by ELISA. Our
      results show that 7 out of the 9 patients studied displayed increased IL-10 mRNA
      expression as well as higher serum IL-10 concentration following steroid
      treatment. In contrast, mRNA expression of two inflammatory cytokines, TNFalpha
      and IFNgamma, decreased following steroid therapy. In vitro experiments employing
      normal PBMC showed that methylprednisolone (MP) upregulated IL-10 expression as
      determined by measuring mRNA levels, flow cytometry of intracytoplasmic protein
      concentration, and the amount of secreted protein. Peak responses of secreted IL
      10 by PBMC cultured cells treated with MP were obtained at 48 h. The effect was
      steroid-specific as IL-10 expression reversed to baseline levels in the presence
      of the glucocorticoid receptor antagonist RU486. Contrary to the effect of MP on
      the spontaneous expression of IL-10, this drug downregulated LPS-induced IL-10
      synthesis. In fact, the concentration of IL-10 in LPS-induced IL-10 secretion
      from normal PBMC decreased upon addition of MP to cell cultures. Thus, it seems
      that MP exerts an opposite effect on the spontaneous and LPS-induced IL-10
      production. Our studies indicate that GCs may control inflammatory responses by
      upregulating production of the immunosuppressor cytokine IL-10.

PMID- 9630161
TI  - No increase in blood-brain barrier permeability after intraperitoneal injection
      of endotoxin in the rat.
AB  - Reactions mediated by the brain are part of the response to intraperitoneal
      administration of endotoxin, a model of gram-negative bacterial infection. To
      test the hypothesis that a compromised blood-brain barrier (BBB) may contribute
      to these reactions, the integrity of the BBB was measured following
      lipopolysaccharide administration. Rats received intraperitoneal injections of 50
      microg/kg or 2 mg/kg of endotoxin. Brain uptake of a macromolecular vascular
      marker, 3H-labelled rat serum albumin, and of a poorly permeable low molecular
      weight substance, [14C]sucrose, was then measured with the intravenous bolus
      injection method. Compared to controls, neither dose of endotoxin affected the
      BBB permeability for these tracers. This was true when brain uptake was measured
      5 min or 2 h after lipopolysaccharide injection. It is concluded that
      intraperitoneal endotoxin even at a high dose does not acutely disrupt the BBB.

PMID- 9630162
TI  - Treatment with P2 protein peptide 57-81 by nasal route is effective in Lewis rat
      experimental autoimmune neuritis.
AB  - Experimental autoimmune neuritis (EAN) is a CD4+ T cell-mediated autoimmune
      disorder of the peripheral nervous system (PNS) that can be actively induced in
      susceptible animal species and strains by active immunization with PNS myelin +
      Freund's complete adjuvant (FCA). EAN represents an animal model for studying the
      immunopathogenesis and treatment of Guillain-Barre syndrome (GBS), which is a
      major inflammatory demyelinating disease of the PNS in humans. Here, we report
      that treatment by nasal administration of the neuritogenic peptide 57-81 of the
      PNS myelin component, P2 protein, dose-dependently suppressed EAN severity and
      shortened clinical EAN. Clinical EAN relapse induced by rechallenge with BPM +
      FCA was also prevented in EAN rats receiving high dose P2 peptide. P2 peptide
      induced suppression of EAN was associated with PNS antigen specific T cell
      hyporesponsiveness reflected by lymphocyte proliferation, numbers of PNS antigen
      reactive IFN-gamma secreting and IFN-gamma mRNA expressing lymph node cells, but
      elevated levels of PNS antigen reactive TGF-beta mRNA secreting cells. Reduced
      CD4+ T cell and macrophage infiltrations within the PNS were also observed. Based
      on these observations, nasal autoantigen administration should be further
      evaluated, considering its possible future use in GBS.

PMID- 9630163
TI  - Linomide suppresses acute experimental autoimmune encephalomyelitis in Lewis rats
      by counter-acting the imbalance of pro-inflammatory versus anti-inflammatory
      cytokines.
AB  - Linomide (quinoline-3-carboxamide) is a synthetic immunomodulator that suppresses
      several experimental autoimmune diseases. Here we report the effects of Linomide
      on experimental autoimmune encephalomyelitis (EAE), a CD4+ T cell-mediated animal
      model of multiple sclerosis (MS). EAE induced in Lewis rats by inoculation with
      homogenized guinea pig spinal cord and Freund's complete adjuvant was strongly
      suppressed by Linomide administered daily subcutaneously from the day of
      inoculation. Linomide dose-dependently delayed the interval between immunization
      and onset of clinical EAE, and reduced severity of EAE symptoms. These clinical
      effects were associated with dose-dependent down-modulation of myelin antigens
      induced T cell responses and by suppression of the proinflammatory cytokines IFN
      gamma and TNF-alpha, and upregulation IL-4, IL-10 and TGF-beta as evaluated by in
      situ hybridization for mRNA expression in spleen mononuclear cells and spinal
      cord sections. These findings suggest that Linomide could be useful in certain T
      cell dependent autoimmune diseases.

PMID- 9630164
TI  - VIP and PACAP enhance IL-6 release and mRNA levels in resting peritoneal
      macrophages: in vitro and in vivo studies.
AB  - Vasoactive intestinal peptide (VIP), a neuropeptide produced by lymphocytes has
      been previously reported to modulate cytokine expression in T lymphocytes. In
      this study, we investigated the effects of VIP and of the structurally related
      neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP38) on the
      production of IL-6 in unstimulated murine peritoneal macrophages. Both
      neuropeptides stimulate rapidly, specifically, and similarly the production of IL
      6, exerting their action through two different receptor/signal transduction
      systems, i.e., primarily through the binding to VIP1/PACAP receptor followed by
      adenylate cyclase activation, and partially through the activation of protein
      kinase C following binding to PACAP-R. VIP and PACAP38 regulate the production of
      IL-6 at a transcriptional level, affecting the de novo synthesis of this
      cytokine. The stimulatory in vitro effect correlates with the stimulation of IL-6
      expression and release in vivo. These studies suggest that VIP/PACAP play a role
      in immune system homeostasis, participating in the intricate cytokine network and
      controlling local immune responses. In addition, the understanding of the factors
      that regulate the expression and release of IL-6 by macrophages is important for
      the elucidation of the role of IL-6 in health and disease.

PMID- 9630165
TI  - A host defense role for a natural antiviral substance in the nervous system.
AB  - The pathogenesis of virus infections of the nervous system (NS) is regulated by
      host defenses. The defensive role of a major constitutive antiviral substance was
      studied by determining its distribution in the human nervous system, its
      concentration and the ability of this viral inhibitor to protect mice against
      viral infection. The 4000 kDa inhibitor complex in the human nervous system was
      detected in brain gray and white matter, spinal cord, and sciatic nerve but not
      in human cerebrospinal fluid. The inhibitor was found in the extracellular medium
      incubated with minced murine brain. The inhibitory titer ranged from
      approximately 50 to 200 antiviral units per gram against polio 1, Semliki Forest,
      Banzi, mengo, Newcastle disease and herpes simplex 1 viruses. The inhibitor is
      composed of lipid and essential protein and carbohydrate moieties as determined
      by enzymatic inactivation. Protection of inhibitor-treated mice was demonstrated
      against both an alphavirus and a picornavirus. Thus a natural defensive role for
      the broadly antiviral inhibitor is suggested by its constitutively high
      concentration, wide distribution in nervous system tissues, presence in
      extracellular fluid and its ability to provide protection in infected mice.

PMID- 9630166
TI  - Kinase inhibitors abrogate IFN-gamma-induced class II transactivator and class II
      MHC gene expression in astroglioma cell lines.
AB  - Multiple kinase events, involving both tyrosine (tyr) kinase and serine/threonine
      (ser/thr) kinase activity, are required for IFN-gamma-induced class II MHC mRNA
      and protein expression in primary rat astrocytes. In this study, we examined the
      necessity of ser/thr and tyr kinase activity for IFN-gamma-induced stimulation of
      class II MHC gene expression in the human astroglioma cell lines CRT and CH235,
      as well as the involvement of these kinases in IFN-gamma-induced expression of
      the class II transactivator (CIITA), a protein critical for IFN-gamma-induced
      transcription of class II MHC genes. We show that general ser/thr kinase
      inhibitors, inhibitors of the ser/thr kinase mitogen-activated protein kinase
      (MAPK), and tyr kinase inhibitors reduce IFN-gamma-induced class II MHC mRNA and
      protein expression in a dose-dependent manner. As well, these inhibitors abrogate
      IFN-gamma-induced CIITA mRNA expression in the astroglioma cell lines. We have
      further demonstrated that cells constitutively expressing the CIITA protein
      (2fTGH.CIITA) show no decrease in CIITA or class II MHC mRNA expression in the
      presence of ser/thr and tyr kinase inhibitors. Collectively, these data indicate
      that ser/thr kinase activity, possibly MAPK, and tyr kinase activity are required
      for IFN-gamma-induced expression of CIITA mRNA, and the subsequent expression of
      class II MHC genes.

PMID- 9630167
TI  - Raised CSF levels of soluble adhesion molecules across the clinical spectrum of
      multiple sclerosis.
AB  - Endothelial activation is considered an important step in multiple sclerosis (MS)
      lesion formation, elevated cerebrospinal fluid (CSF) and serum levels of certain
      adhesion molecules being associated with varying stages of disease activity and
      clinical course. CSF and serum sVCAM-1, sICAM-1, sE-selectin and sL-selectin were
      measured by ELISA in 16 primary progressive (PPMS), 16 secondary progressive
      (SPMS) and 43 relapsing-remitting MS patients (RRMS) and compared with 20
      inflammatory (IND) and 46 non-inflammatory neurological disease (NIND) controls.
      CSF sVCAM-1 and sICAM-1 were increased in all MS groups vs. NIND with no
      significant differences between the MS groups. CSF sE-selectin (p = 0.007) and
      the sE-selectin index (p = 0.01) were elevated in PPMS vs. RRMS in relapse,
      whilst serum sE-selectin was significantly raised in PPMS compared to RRMS in
      remission (p = 0.005), RRMS in relapse (p = 0.004), NIND (p = 0.03) and IND (p =
      0.05). Adhesion molecule levels in both progressive MS groups were similar. These
      results provide evidence for a distinct inflammatory component in PPMS and for
      immunological heterogeneity between the clinical subgroups of MS.

PMID- 9630168
TI  - Behaviorally conditioned effects of Cyclosporine A on the immune system of rats:
      specific alterations of blood leukocyte numbers and decrease of granulocyte
      function.
AB  - Immunosuppression induced by Cyclosporine A (CsA) can be behaviorally
      conditioned. It is unknown, however, whether a taste aversion paradigm using CsA
      as an unconditioned stimulus (UCS) induces alterations of blood leukocyte numbers
      and function. Results obtained by three-colour flow cytometry and granulocyte
      chemiluminescence response demonstrate that in conditioned rats, absolute numbers
      of lymphocyte subsets, including B, CD8+ T cells and CD4+ naive and memory T
      cells, and granulocyte numbers and function were significantly decreased. In
      contrast to the conditioned response, CsA treatment alone increased lymphocyte
      numbers and did not affect granulocyte function. Thus, our data demonstrate that
      behaviorally conditioned CsA effects can be monitored in the blood. In addition,
      results indicate that the CNS mediates the behaviorally conditioned
      immunosuppression by reducing the availability and function of granulocytes and
      lymphocytes.

PMID- 9630169
TI  - The immune status of the myelin deficient rat and its immune responses to
      transplanted allogeneic glial cells.
AB  - This study examined the immunological responsiveness of the myelin deficient (md)
      rat, and its immune response to transplanted allogeneic glial cells, with and
      without immunosuppression therapy. Skin grafts from an ACI strain of rat were
      found to be acutely rejected by Wistar md rats. Anti-donor cytotoxic antibody was
      produced and alloreactive T helper cells were expanded in these mutants after
      skin sensitization. Equivalent high frequencies of precursor cytotoxic T
      lymphocytes (pCTLs) specific to the ACi MHC antigens were observed in both normal
      controls and mutants. An immune response was noted when allogeneic glial cells
      were transplanted into the spinal cords of md rats, which was effectively
      suppressed for 2 weeks post transplantation by treatment with either cyclosporin
      A (CsA) or a monoclonal antibody to the interleukin-2 receptor (IL-2R). These
      results demonstrate that md rats are immunocompetent, but that CNS allograft
      rejection can be prevented by immunosuppressive agents.

PMID- 9630170
TI  - ELI-spot of Th-1 cytokine secreting PBMC's in multiple sclerosis: correlation
      with MRI lesions.
AB  - The Th1-like cytokines, interleukin 2 (IL-2), interferon gamma (IFN-gamma), and
      lymphotoxin alpha (LT-alpha) have been implicated in the immunopathogenesis of
      multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE), an
      animal model of immune mediated demyelination. These cytokines have been
      associated with opening of the blood brain barrier (BBB) in EAE and in vitro, but
      not in MS. We used an enzyme-linked immunospot (ELI-spot) assay to measure
      relative numbers of cytokine-secreting peripheral blood mononuclear cells (PBMC)
      from eight MS patients who were followed with serial monthly contrast-enhanced
      head magnetic resonance imagings (MRI) and phlebotomy. We found a significant
      positive correlation between changes in IL-2 secreting cells and MRI lesions over
      a 6-month time period. There was a weaker association between contrast-enhancing
      MRI lesions and IFN-gamma or LT-alpha secreting cells. These data are the first
      to show a significant positive correlation between any cytokine and serial
      gadolinium (Gd-) MRI disease activity in MS patients. The association between IFN
      gamma and LT-alpha secretion and MRI lesions is less clear.

PMID- 9630172
TI  - Neoangiogenesis and sinusoidal "capillarization" in dysplastic nodules of the
      liver.
AB  - The blood supply of hepatocellular carcinoma (HCC) is primarily arterial. Recent
      studies reported differences of vascular, especially arterial, supply among low-
      and high-grade dysplastic nodules and HCC. We assessed arterialization using
      monoclonal antibody specific for smooth muscle actin as well as simultaneous
      changes in sinusoidal capillarization in cirrhotic nodules, dysplastic nodules,
      and HCC. We immunohistochemically stained 56 cirrhotic nodules, 20 low-grade
      dysplastic nodules, 27 high-grade dysplastic nodules, and 20 HCCs for alpha
      smooth muscle actin (to identify unpaired arteries (i.e., arteries not
      accompanied by bile ducts) and CD34 (indicating sinusoidal capillarization).
      Distribution and number of unpaired arteries and distribution of sinusoidal
      capillarization were graded semiquantitatively. Unpaired arteries were rare in
      cirrhotic nodules, significantly more common in dysplastic nodules of both types
      (p < 0.00001), and most common in HCC. Sinusoidal capillarization was least
      common in cirrhotic nodules, significantly more common in dysplastic nodules (p <
      0.0035), and most common in HCC. No topographic relationship between unpaired
      arteries and sinusoidal capillarization was identified. These findings showed
      that (1) distributions of sinusoidal capillarization and unpaired arteries in
      dysplastic nodules are intermediate between those in cirrhotic nodules and HCC,
      supporting dysplastic nodules as premalignant lesions; (2) unpaired arteries are
      histologically useful for distinguishing dysplastic nodules from large cirrhotic
      nodules; and (3) areas of sinusoidal capillarization within dysplastic nodules
      are unrelated to location of arterialization.

PMID- 9630171
TI  - Angioimmunoblastic lymphoma (AILD-type T-cell lymphoma) with hyperplastic
      germinal centers.
AB  - Angioimmunoblastic T-cell lymphoma (or angioimmunoblastic lymphadenopathy with
      dysgammaglobulinemia [AILD]) was originally considered to be an abnormal immune
      reaction in which reactive follicles with germinal centers (GCs) are usually
      absent. When hyperplastic GCs are present along with an angioimmunoblastic
      reaction, the lesion has been interpreted as a benign hyperimmune reaction. We
      report seven patients with angioimmunoblastic T-cell lymphoma (AITL) who
      initially had hyperplastic GCs, shown to be malignant lymphoma by further studies
      and clinical follow-up. Clonal T-cell populations were observed in all specimens
      evaluated, and sequential biopsies showed histologic progression to typical AITL
      in two patients. Clinical presentation was characterized by generalized
      lymphadenopathy of acute onset, constitutional symptoms, hepatosplenomegaly, skin
      rash, and polyclonal hypergammaglobulinemia in five patients; regional adenopathy
      preceded generalized adenopathy in two patients. Five patients had rapid
      progression of disease, and three patients whose treatment was delayed due to
      inadequate evidence to diagnose lymphoma died of infection. The initial biopsy
      findings of each patient were similar and showed angioimmunoblastic
      proliferation, hyperplastic GCs with ill-defined borders, and interfollicular
      tingible-body macrophages. These GCs differed from occasional residual follicles
      of typical AITL in that the GCs were enlarged and hyperplasia of follicular
      dendritic cells was not seen. Diagnostic clear cells were not observed. Apoptotic
      bodies were markedly increased and bcl-2+ lymphocytes were sparse compared with
      typical AITL. Results of in situ hybridization for Epstein-Barr virus were
      positive in each case. We conclude that hyperplastic germinal centers with ill
      defined borders and frequent interfollicular tingible-body macrophages occur in a
      histologic variant of AITL that is necessary to recognize for early diagnosis and
      treatment.

PMID- 9630173
TI  - Carcinomalike monotypic epithelioid angiomyolipoma in patients without evidence
      of tuberous sclerosis: a clinicopathologic and genetic study.
AB  - We report the clinicopathologic, immunohistochemical, ultrastructural, and
      genetic features of an unusual renal tumor composed of large, atypical, densely
      packed, clear/eosinophilic epithelioid cells. Three patients, two men and one
      woman (ages 31, 36, and 60 years of age, respectively), had abdominal pain.
      Morphologically, all cases showed aggressive features (largeness, atypical cells,
      sarcomatoid features, necrosis, and, in one case, invasion of the renal vein).
      Despite the marked morphologic resemblance of these tumors to high-grade
      sarcomatoid renal cell carcinoma, their phenotype (HMB45+, CD68+/-, actin+/-, and
      vimentin and keratin negative) is in contrast to that observed in epithelial
      tumors and parallels the phenotypic profile of angiomyolipoma. Ultrastructural
      analysis showed the presence of glycogen, mitochondria, and prominent electron
      dense, membrane-bound granules in the neoplastic cells, and the absence of
      melanosomes or premelanosomes. Genetic study, performed using polymerase chain
      reaction from paraffin sections, showed a loss of heterozygosity at the TSC2
      containing region on 16p in one case, and on 3p in two cases, showing that
      multiple genetic alterations are taking place in these tumors. Follow-up has
      shown local recurrence in one case after 6 years, and the patient died 1 year
      later of cardiorespiratory failure. The other two patients are well after 26 and
      10 months. All three patients were evaluated for signs of tuberous sclerosis, and
      findings were negative. We suggest that these tumors should be considered close
      relatives of the angiomyolipoma variants, composed purely of perivascular
      epithelioid cells. More cases and longer follow-up durations are needed to fully
      evaluate its prognostic implication.

PMID- 9630174
TI  - Poorly differentiated synovial sarcoma: immunohistochemical distinction from
      primitive neuroectodermal tumors and high-grade malignant peripheral nerve sheath
      tumors.
AB  - Synovial sarcoma is a relatively common sarcoma in adults, which in its classic
      bimorphic form infrequently poses a diagnostic problem. Monomorphic spindled
      variants, as well as the less common poorly differentiated variants, may be
      confused with other soft-tissue sarcomas; the poorly differentiated variant
      (PDSS), in particular, may be histologically indistinguishable from other small,
      blue, round cell tumors, including primitive neuroectodermal tumors (PNETs).
      Detection of the synovial sarcoma-associated t(X;18) by either cytogenetic or
      molecular genetic approaches may be necessary to confirm the diagnosis of
      synovial sarcoma in difficult cases. We evaluated 10 cases of PDSS from eight
      patients using a panel of antibodies (including those to intermediate filament
      proteins, nerve-sheath associated markers, and neuronal and neuroectodermal
      associated markers) in order to better establish the immunophenotype of this
      tumor and to help distinguish it from the tumors with which it may be confused,
      particularly PNETs and high-grade malignant peripheral nerve sheath tumors
      (MPNSTs). Our results showed PDSS to have significant immunophenotypic overlap
      with both PNETs and MPNSTs. In most instances these three entities may be
      differentiated by a panel of antibodies that should include those to both low and
      high molecular weight cytokeratins, epithelial membrane antigen, type IV
      collagen, CD99, CD56, and S-100 protein. Our results also suggest that synovial
      sarcoma may be a tumor showing combined neuroectodermal and nerve sheath
      differentiation--perhaps because of translocation-associated expression of
      specific proteins--rather than a carcinosarcoma of soft tissues or a tumor of
      specialized arthrogenous mesenchyme.

PMID- 9630175
TI  - Angiosarcoma of soft tissue: a study of 80 cases.
AB  - The clinicopathologic, immunohistochemical, and ultrastructural features of soft
      tissue angiosarcomas are not well defined. Eighty cases of angiosarcoma that
      involved the deep subcutis, skeletal muscle, retroperitoneum, mesentery, and
      mediastinum are reported. The lesions occurred in 50 male and 30 female patients
      who were 5-97 years of age; the peak incidence was in the seventh decade of life.
      A variety of associated conditions were documented in 20 of these cases,
      including a history of other neoplasms (some irradiated), synthetic vessel
      grafts, heritable conditions, and prior trauma or surgery. The angiosarcomas
      occurred in the extremities (n = 43 cases), trunk (n = 28), and the head and neck
      (n = 9) regions, with the thigh and the retroperitoneum being the most common
      sites. They often were characterized as enlarging, painful masses of several
      weeks' duration and were occasionally associated with acute hemorrhage, anemia,
      or a coagulopathy. The tumors measured 1-15 cm in diameter (median 5 cm) and
      frequently were hemorrhagic and multinodular. There was a wide morphologic
      spectrum within and between cases, including areas similar to cavernous and
      capillary hemangioma, Dabska tumor, spindle cell and epithelioid
      hemangioendothelioma, various spindle cell sarcomas, or carcinoma.
      Histologically, epithelioid angiosarcoma was the most frequently observed
      pattern; 70% of cases had epithelioid cells that were arranged in nests,
      clusters, papillae, and gaping vascular channels. Hemorrhage tended to obscure
      the diagnosis in several cases and often was associated with papillary
      endothelial hyperplasia-like areas. All 42 cases studied immunohistochemically
      stained at least focally for Factor VIII-related antigen, and nearly all stained
      strongly for vimentin, which accentuated the endothelial cells and vessel lumen
      formation. CD34 antigen was detected in 74% of cases, BNH9 in 72%, and
      cytokeratins in 35%. Epithelial membrane antigen, S-100 protein, and HMB45 were
      not detected. Fifty-five percent of the tumors had intracytoplasmic aggregates of
      laminin. Immunostains for alpha-smooth muscle actin demonstrated a prominent
      pericytic component in several tumors (24%). Ki67 immunostains with MIB1
      indicated high proliferative activity (> or =10%) in 72% of cases. p53
      immunoreactivity (>20% nuclear staining) was observed in 20% of cases.
      Ultrastructural studies performed on poorly differentiated areas of 12 cases
      showed groups of cells, which were frequently epithelioid, surrounded by basal
      lamina, and closely associated with pericytes, along with intercellular and
      intracellular lumina with or without red blood cells. Whorls of abundant
      intermediate filaments, occasional tonofilamentlike structures, and pinocytotic
      vesicles also were noted. In contrast to the findings of others, Weibel-Palade
      bodies were not seen. Follow-up in 49 cases (61%) showed that 53% of patients
      were dead of disease at a median interval of 11 months, whereas 31% had no
      evidence of disease at a median interval of 46 months. The remaining patients
      were either alive with disease (14%) or alive but disease status was unknown
      (2%). There were local recurrences in 20% of cases and distant metastases in 49%,
      most frequently to the lungs, followed by the lymph nodes, soft tissues, bone,
      liver, and other sites. These results indicate that angiosarcoma of soft tissue
      is a high-grade sarcoma. Older patient age, tumor location in the
      retroperitoneum, and larger tumor size as well as detection of MIB1 in > or =10%
      of the tumor cell population were all associated with a poorer prognosis.

PMID- 9630176
TI  - Mucinous cystadenocarcinoma of the breast.
AB  - Four unusual cases of primary mammary mucinous cystadenocarcinoma composed
      predominantly of tall columnar cells with abundant intracytoplasmic mucin are
      reported; they were multicystic and appeared virtually identical to mucinous
      cystadenocarcinomas of the ovary and pancreas. Three of the women were white and
      one was black, they ranged in age from 49 to 67 years (average 58), and they had
      tumors that ranged from 0.8 to 19 cm in diameter. Microscopically, the tumors
      were characterized by cystic spaces lined by predominantly bland-appearing
      columnar mucinous cells with stratification, tufting, and papillary formations.
      Varying degrees of cytologic atypia were focally evident, with gradual loss of
      the intracytoplasmic mucin and transformation to an eosinophilic squamoid cell
      population. Multifocal invasion generally emanated from these eosinophilic,
      squamoid areas in all cases. All four tumors displayed immunoreactivity for MIB-1
      (Ki-67) in a relatively high percentage of cells and failed to show
      immunoreactivity for estrogen receptors and progesterone receptors. All four
      stained positively with cytokeratin 7 (CK7) but were negative with cytokeratin 20
      (CK20). Mastectomy and axillary lymph node dissection were performed in three
      cases and lumpectomy with lymph node dissection in the remaining case. Lymph node
      metastases, identified in only one patient, retained the distinctive morphology.
      Three of the patients are alive without evidence of disease 11, 22, and 24 months
      after the diagnosis; the fourth is a recent case. These tumors are a rare,
      clinicopathologically distinct type of primary breast carcinoma that should be
      distinguished from typical mucinous (colloid) carcinomas of the breast and, more
      importantly, metastases from other sites.

PMID- 9630177
TI  - Epidermoid cyst of the spleen with CA19-9 or carcinoembryonic antigen
      productions: report of three cases.
AB  - True splenic cyst is a relatively rare disease, and the majority of the cases are
      classified as epidermoid cysts. Three cases of epidermoid cysts in the spleen or
      accessory spleen were studied using an immunohistochemical technique and staining
      for mucin. In case 1, serum carcinoembryonic antigen (CEA) and CA19-9, and in
      cases 2 and 3, serum CA19-9, before surgery were markedly elevated, and these
      levels decreased postoperatively. This strongly indicates the relationship
      between the increase of tumor marker levels and the presence of the epidermoid
      cyst. In addition, stratified squamous epithelium in the resected tissues of
      cases 1 and 2 was positive for anti-CEA antibody and anti-CA19-9 antibody, and
      that of case 3 was positive for anti-CA19-9 antibody. This strongly supports CEA
      or CA19-9 production in the squamous epithelium.

PMID- 9630178
TI  - Sertoli cell tumors of the testis, not otherwise specified: a clinicopathologic
      analysis of 60 cases.
AB  - Sixty Sertoli cell tumors of the testis, excluding large cell calcifying and
      sclerosing subtypes, are described. Patient age ranged from 15 to 80 years (mean,
      45 years). The initial manifestation was usually a testicular mass; in 14 cases
      it had been enlarging slowly for a period of up to 14 years (mean 3.7 years).
      Only five patients had testicular pain. Four patients had metastatic disease at
      the time of presentation. All the tumors were unilateral and ranged from 0.3 cm
      to 15 cm (mean 3.6 cm). They were typically well circumscribed. Sectioning
      usually disclosed firm, tan-gray, white, or yellow tissue with areas of
      hemorrhage and a minor cystic component in approximately one third. Microscopic
      evaluation usually revealed diffuse sheets or large, nodular aggregates of tumor
      cells, within which solid or hollow, sometimes dilated, tubules and, less often,
      cords were usually at least focally identifiable. A relatively acellular, often
      vascular, fibrous to hyalinized stroma was frequently conspicuous. The tumor
      cells typically had moderate amounts of pale to lightly eosinophilic cytoplasm,
      but 10 tumors had cells with abundant eosinophilic cytoplasm. Large cytoplasmic
      vacuoles were prominent in 26 tumors. Nuclear atypicality was absent or mild in
      54 cases, moderate in 4 cases, and marked in 2 cases. Mitotic rate ranged from
      less than 1 to 21 per 10 high power fields, with 50 tumors having no or only rare
      mitoses. Vascular space invasion was present in 11 cases and was prominent in 8.
      Follow-up of more than five years (average 8.4 years), or until evidence of
      metastasis was seen, was available for 16 patients. Nine were alive and well with
      no evidence of disease. Four were alive with disease and three died of disease.
      The pathologic features that best correlated with a clinically malignant course
      were as follows: a tumor diameter of 5.0 cm or greater, necrosis, moderate to
      severe nuclear atypia, vascular invasion and a mitotic rate of more than 5
      mitoses per 10 high power fields. Only one of nine benign tumors for which follow
      up data of 5 years or more were available had more than one of these features,
      whereas five of seven malignant tumors had at least three.

PMID- 9630179
TI  - C-cell hyperplasia and medullary thyroid carcinoma in patients routinely screened
      for serum calcitonin.
AB  - Routine screening of calcitonin serum levels in patients with nodular thyroid
      disorders has led to an increased rate of total thyroidectomies. We investigated
      prevalence and interrelationship of C-cell hyperplasia (CCH) and medullary
      thyroid carcinoma (MTC) in patients with thyroid and parathyroid disorders that
      showed increased calcitonin serum levels detected by routine screening. Within
      two years, 30 (mean age, 60 +/- 14 years) of 667 patients had a pentagastrin
      stimulated calcitonin level of more than 100 pg/mL. All 30 underwent total
      thyroidectomy and were tested for germ-line mutations of the ret protooncogene.
      Entire surgical specimens were blocked, and C-cell disorders were assessed using
      conventional histology and immunohistochemistry. C-cell hyperplasia was defined
      by the presence of more than 50 C cells/l low-power field in both lobes and was
      classified as focal, diffuse, nodular, or neoplastic. Nineteen patients
      (female/male = 14/5) had MTC, and 11 males but no females had CCH only. Six of 16
      patients with sporadic MTC had concomitant CCH. Three patients were index cases
      of new MTC families. We conclude that MTC with concomitant CCH is an unreliable
      marker for hereditary MTC risk and that CCH has a preneoplastic potential in the
      absence of germ-line mutations. In this series, CCH alone was not found in
      females.

PMID- 9630180
TI  - Development of gastrointestinal beta2-microglobulin amyloidosis correlates with
      time on dialysis.
AB  - Dialysis-associated beta2-microglobulin (beta2m) amyloidosis affects
      predominantly musculoskeletal tissue, but visceral involvement also occurs. To
      evaluate the clinical significance and prevalence of gastrointestinal beta2m
      amyloidosis, we studied hemodialysis patients admitted for gastrointestinal
      related complaints. Hemodialysis patients (excluding those with non-beta2m
      amyloidosis) who were admitted with gastrointestinal complaints from 1984 to 1994
      were identified. Gastrointestinal tissues from patients with available autopsy or
      surgical specimens were examined using hematoxylin and eosin stain, Congo red
      stain, and beta2m immunostain. Each case was evaluated independently by two
      pathologists and scored for quantity and location of beta2m amyloid and
      associated pathology. Of 24 patients, eight (four men and 4 women) had beta2m
      amyloid deposits within the gastrointestinal tract. Acute clinical presentation
      ranged from abdominal pain to gastrointestinal bleeding and was not significantly
      different for patients with or without gastrointestinal beta2m amyloid deposits.
      However, the mean time on dialysis of 15.3 +/- 5.7 years (range 6-24 years) for
      patients with gastrointestinal beta2m amyloidosis was significantly greater than
      that of patients without gastrointestinal beta2m amyloidosis (10.5 +/- 7.0 years,
      range <1 to 22 years, p < 0.05). Vascular histopathology ranged from mild focal
      thickening of vessel walls to massive vascular beta2m amyloid deposition with
      thrombosis. Extravascular beta2m amyloid ranged from mild to severe with marked
      expansion of the submucosa. Mucosal pathology ranged from none to severe
      ulceration. The degree of beta2m amyloid and the associated pathology tended to
      increase in severity with time on dialysis. Gastrointestinal beta2m amyloid
      deposition is an underappreciated complication of chronic hemodialysis that is
      significantly associated with increased time on dialysis. Gastrointestinal beta2m
      amyloidosis should be considered in any patient on hemodialysis 10 years or more
      who has gastrointestinal symptoms and can be identified in resection specimens as
      well as some biopsy specimens. Congo red stain and beta2m immunostains may be
      necessary for sensitive histopathologic evaluation of gastrointestinal beta2m
      amyloidosis.

PMID- 9630181
TI  - Xanthomatous hypophysitis.
AB  - Inflammatory lesions of the hypophysis include lymphocytic hypophysitis,
      pituitary abscess, and granulomatous inflammation, with or without specific
      infections (i.e., sarcoidosis, mycobacteria). These lesions are known to mimic
      pituitary neoplasms. We report the clinical and pathologic findings in three
      patients who underwent transsphenoidal resection for presumed pituitary adenoma.
      Two were women aged 30 years (one with a 5-month history of headache, the other
      with a 1-year history of menstrual irregularity) and one was a 12-year-old girl
      with headache, nausea, and diabetes insipidus. Preoperative endocrinologic
      studies showed increased prolactin in one patient and normal serum thyroid
      stimulating hormone and prolactin levels in another. By magnetic resonance
      imaging (MRI), the first case had a 1.2-cm mass with increased signal on T1 and
      isointensity on T2, ring enhancement after gadolinium, and lateral deviation of
      the pituitary stalk. The second patient had a 1.1-cm "cystic" mass seen during
      magnetic resonance imaging with adjacent bony changes seen during computed
      tomography. In the third, computed tomography showed a hypodense pituitary mass
      that enlarged during 1-month observation. At surgery, abnormal soft tissue
      surrounded liquefied material in the anterior pituitary in all cases. Histologic
      studies showed fragments of intact normal anterior pituitary with preserved
      vascular and reticulin network and regions of anterior pituitary infiltrated by
      foamy histiocytes. Other fragments resembled granulation tissue, and some
      consisted of acellular debris. Histiocytes were immunoreactive for the macrophage
      marker CD68 and negative for S-100 and CD1a. Ultrastructurally, the normal
      adenohypophysis was permeated by lipid-laden macrophages. There were no well
      formed granulomas or giant cells, hemosiderin, acid-fast bacilli, or fungi.
      Serial sections and keratin immunostains failed to identify an epithelial cyst
      lining or keratin among the debris. We propose the term "xanthomatous
      hypophysitis" for this lesion.

PMID- 9630182
TI  - Liver carcinoma in PiZ alpha-1-antitrypsin deficiency.
AB  - One hundred sixty-four consecutive cases of primary liver carcinoma were
      evaluated for tumor type, (i.e., hepatocellular carcinoma [HCC],
      cholangiocarcinoma [CC], and combined hepatocholangiocarcinoma [CHCC]), and for
      signs of alpha-1-antitrypsin deficiency (AATD) in the surrounding liver tissue.
      Hepatocellular globular alpha-1-antitrypsin deposits, as detected by a monoclonal
      antibody to the mutant PiZ alpha-1-antitrypsin (AAT), were seen in 13 cases
      (7.9%). With regard to tumor type, 4 of 111 HCC cases (3.5%), but 4 of 37 CC
      cases (10.5%), and even 5 of 16 CHCC cases (30%) were positive for this
      antitrypsin variant. In all but 1 of 13 cases of alpha-1-antitrypsin deficiency,
      the carcinoma developed in noncirrhotic liver tissue of elderly people (mean age,
      62.9 years). In three patients, a heterozygous state of ATT (PiMZ) could be
      revealed using isoelectric focusing or direct genetic analysis. We conclude from
      our findings that CHCC and CC especially might be associated with PiZ alpha-1
      antitrypsin deficiency. Primary liver carcinoma might develop even in a
      heterozygote state of PiZ alpha-1-antitrypsin deficiency without concurrent liver
      disease. Furthermore, liver cirrhosis is not a precondition for these tumors.

PMID- 9630184
TI  - Basaloid squamous cell carcinoma: a distinctive human papilloma virus-related
      penile neoplasm: a report of 20 cases.
AB  - Most penile neoplasms are squamous cell carcinomas (SCC), but there are subtypes
      that show morphologic and possibly etiologic differences. Clinicopathologic
      features of 20 patients with basaloid carcinoma (BC), an unusual variant of
      squamous cell carcinoma, are presented. Median age was 52 years, and all tumors
      were located in the glans, three confined to the perimeatal region. Average tumor
      size was 3.8 cm. Microscopically, nests of small, basophilic cells with numerous
      mitosis were present. Human papillomavirus DNA sequences (type 16), using the
      polymerase chain reaction (PCR), were found in 9 of 11 cases. Differential
      diagnosis included urethral transitional cell, basal cell, small cell
      neuroendocrine, and metastatic carcinoma. Factors more significantly associated
      with regional metastasis and mortality were tumor thickness greater than 10 mm
      and infiltration of the corpus cavernosum. A comparison with typical squamous
      cell carcinoma showed basaloid carcinoma to have a higher histologic grade, a
      deeper invasion of penile anatomic levels, and a higher mortality rate. Of 17
      patients observed, 10 were dead of disease (average time, 34 months), one was
      alive with disease 6 months after diagnosis, and 5 were alive and free of disease
      (average time, 71 months); the remaining patient died of other causes. Basaloid
      carcinoma is a distinctive morphologic subtype of squamous cell carcinoma
      frequently associated with the human papilloma virus.

PMID- 9630183
TI  - MIB-1 as a predictor of response in lung allografts with moderate acute cellular
      rejection.
AB  - The major obstacle that long-term lung transplant recipients face is
      bronchiolitis obliterans. Prior episodes of acute rejection, specifically their
      frequency, persistence, and severity, are important predictors of bronchiolitis
      obliterans. Many cells contribute to the damage of acute rejection, and there is
      no sole cell type that can predict persistent rejection or bronchiolitis
      obliterans. In this study we evaluated 48 transbronchial biopsy samples from
      various grades of acute rejection with the proliferation marker MIB-1 and
      attempted to retrospectively predict response to standard corticosteroid in a
      subpopulation of nine responders and nine nonresponders, all with grade A3
      rejection. We then characterized the proliferating cells by double labeling with
      MIB-1 and L26, CD3, OPD4, or KP1. Our results indicate that the proliferating
      cells in acute lung rejection are a heterogeneous pool of T- and B-lymphocytes, T
      helper cells, macrophages, endothelial cells, and possibly parenchymal cells, and
      that MIB-1 is a valuable tool in the evaluation of total cellular activity in
      this setting. In addition, the overall proliferation rate, defined as the most
      intense proliferation rate regardless of location in the biopsy, closely matches
      the grade of acute rejection. Finally, a low lesional proliferation rate, defined
      as the proliferation rate at the site of perivascular inflammation diagnostic of
      acute rejection, is an indicator of excellent response to therapy and may have
      potential clinical importance.

PMID- 9630185
TI  - Benign epithelioid schwannoma.
AB  - Benign schwannoma (neurilemoma) has various morphologic patterns that may cause
      problems in differential diagnosis. Although an epithelioid variant of malignant
      schwannoma simulating carcinoma and melanoma is well recognized, a benign
      counterpart has not yet been defined. In the current study, we describe five
      cases of benign epithelioid schwannoma that were in the subcutis (four cases) and
      the neck of the urinary bladder (one case). The tumors occurred in adults 28-73
      years of age, were 1-4.5 cm in diameter, were well circumscribed and cellular,
      and were composed of epithelioid cells arranged in cords and nests. The benign
      nature of the lesions was evident by a constellation of features, including small
      size, sharp circumscription, bland morphology, low proliferative activity (four
      of five had < or =1% Ki67 immunostaining), and a benign clinical course after
      either marginal or intralesional excision. All cases had some features of classic
      schwannoma light microscopically and a high degree of Schwann cell
      differentiation both ultrastructurally and immunohistochemically. The recognition
      of benign epithelioid schwannoma is important because it may be misinterpreted as
      a malignant neuroectodermal, mesenchymal, epithelioid, or melanocytic tumor.

PMID- 9630186
TI  - Pleomorphic adenoma.

PMID- 9630187
TI  - Differentiating ischemic colitis from other colitides.

PMID- 9630188
TI  - Traditional cell metaplasia of cervix: a misnomer.

PMID- 9630189
TI  - Tubulolobular carcinoma of the breast.

PMID- 9630190
TI  - Nuchal fibrocartilagenous pseudotumor.

PMID- 9630191
TI  - Pulmonary hypertension complicating mixed connective tissue disease.

PMID- 9630192
TI  - Evaluation of bronchoscopic findings in patients with metastatic pulmonary tumor.
AB  - To clarify the bronchoscopic findings in metastatic spread to the bronchi, we
      analyzed the records of 65 cases of metastatic pulmonary disease in which
      fiberoptic bronchoscopy had been done. Forty-five patients (69.2%) had abnormal
      bronchoscopic findings. These patients could be divided into three groups,
      according to bronchoscopic findings and route of metastatic spread to the
      bronchi: endobronchial metastasis (n=15), bronchial involvement (that is, direct
      extension to the bronchi from adjacent metastatic foci, n=15), and lymphangitis
      carcinomatosa (n=15). Breast cancer and colon cancer were common in cases of
      endobronchial metastasis, and the bronchial tumor often presented as a polypoid
      or nodular lesion covered with necrotic material. Submucosal swelling with an
      irregular margin and narrowing of the bronchial lumen were seen in cases of
      bronchial involvement. In conclusion, each type of primary extrapulmonary tumor
      is associated with characteristic endobronchial findings of pulmonary metastases
      such as endobronchial metastasis and bronchial involvement, which should be
      discriminated if possible, because of their different metastatic process.

PMID- 9630193
TI  - Nocturnal oxyhemoglobin desaturation and prognosis in chronic obstructive
      pulmonary disease and late sequelae of pulmonary tuberculosis. Respiratory
      Failure Research Group in Japan.
AB  - We prospectively examined the survival rate of 67 chronic obstructive pulmonary
      disease (COPD) and 74 late sequelae of pulmonary tuberculosis (TB seq) patients
      to clarify whether nocturnal oxyhemoglobin desaturation (NOD) could be one of the
      independent factors determining their mortality. The sleep monitoring of arterial
      oxygen saturation (SpO2) and pulmonary function tests were assessed in all
      patients at the time of registration. Forty % of COPD and 24% of TB seq died as
      the direct result of deterioration of chronic respiratory failure during the 7
      year observation period. Cox's proportional hazards analysis showed that NOD was
      an independent prognostic factor in both groups, and this was especially
      prominent when evaluated in terms of sleep lowest SpO2 in COPD and 85%
      desaturation time in TB seq. No significant prognostic factor was observed among
      age, vital capacity percent predicted (%VC), forced expiratory volume in one
      second (FEV(1.0)%) and partial pressure of carbon dioxide (PaCO2). We conclude
      that the degree of NOD can affect mortality in COPD and TB seq.

PMID- 9630194
TI  - Diffusion-weighted magnetic resonance and magnetization transfer imaging in the
      assessment of ischemic human stroke.
AB  - We compared characteristic features in ischemic stroke lesions from the
      hyperacute to the chronic stage on diffusion-weighted (DW) and magnetization
      transfer (MT) images with those on T2-weighted (T2W) images, and assessed changes
      in apparent diffusion coefficient (ADC), MT effect (MTe), and T2 ratios
      (infarct/normal) over time. DW images were particularly useful for detecting
      hyperacute infarcts within 6 hours of onset and in distinguishing acute lesions
      from chronic lesions. ADC ratios were lower within 7 days after onset and rose
      toward 1.0 in the subacute phase, becoming relatively isotense on ADC maps, but
      elevated thereafter. Although MTe ratios were unchanged or only subtly changed in
      the acute stage, they became significantly lower in the subacute and chronic
      stages. These combined magnetic resonance (MR) techniques were useful in the
      assessment of ischemic stroke and facilitated the determination of the age of
      cerebral infarct.

PMID- 9630195
TI  - A huge coronary aneurysm resulting from a coronary artery-to-left ventricle
      fistula.
AB  - A huge coronary aneurysm resulting from a coronary artery-to-left ventricle
      fistula is a rare condition. A 57-year-old male had severe recurrent angina
      attacks. The cause of angina pectoris was a right coronary artery-to-left
      ventricle fistula with a huge coronary aneurysm. The histological examination of
      surgically excised specimens revealed that two vertical smooth muscle layers of
      media of the aneurysm might be associated with dysplasia. Mucoid degeneration was
      also shown in the intima and around the vasa-vasorum. Abnormal hemodynamics
      related to the fistula might have induced these vessel wall changes resulting in
      the huge coronary aneurysm.

PMID- 9630196
TI  - Primary cardiac leiomyosarcoma growing rapidly and causing right ventricular
      outflow obstruction.
AB  - Leiomyosarcomas are extremely rare primary cardiac tumors. We report a rapidly
      growing primary leiomyosarcoma of the right ventricle, which obstructed the right
      ventricular outflow tract within one month after symptom onset in a 68-year-old
      man. Two-dimensional echocardiography was useful in diagnosing the extent and
      progression of the tumor. The tumor was surgically resected on an emergency
      basis, and the right ventricle and pulmonary artery were successfully
      reconstructed. Recurrence of the tumor on the right ventricle was observed, and
      the patient was overcome by sudden dyspnea and died three months after surgery.

PMID- 9630198
TI  - Lingual thyroid presenting as acquired hypothyroidism in the adulthood.
AB  - There are numerous reported cases of lingual thyroid with an obvious prevalence
      in pediatric age. Such ectopic thyroid glands are probably quantitatively
      deficient and thyroid function may be low or at a low normal level. Apparently,
      most cases of ectopic thyroid tissue develop congenital hypothyroidism, the so
      called cretinism. In this report, we describe a very rare adult male case of
      lingual thyroid who developed hypothyroidism in adulthood; the anomaly remained
      undiscovered, being without local common symptoms, and permitted a normal life.

PMID- 9630197
TI  - Retroperitoneal malignant fibrous histiocytoma causing variegated colonic
      lesions.
AB  - A 68-year-old man visited our hospital because of heartburn. A firm mass was
      palpated in the left upper abdominal quadrant. Ultrasonography and computed
      tomography revealed a large left sided retroperitoneal tumor. A barium enema
      examination showed shallow irregularly depressed or elevated lesions. Colonoscopy
      revealed an irregularly shaped ulcer and multiple submucosal masses suggesting
      invasion by an extrinsic malignant tumor. Although colonoscopic biopsy was
      negative, a resected tumor was histologically diagnosed as a malignant fibrous
      histiocytoma (MFH). When such varigated lesions are detected in the colon, MFH
      should be considered, and an attempt to sample the submucosal layer may be
      necessary.

PMID- 9630199
TI  - Cushing's syndrome due to unilateral adrenocortical hyperplasia.
AB  - A 49-year-old woman with Cushing's syndrome due to unilateral adrenal hyperplasia
      is presented. She had developed obesity and menopause for 2 years, but no
      hypertension or hypertrichosis was observed. Although plasma adrenocorticotropin
      and serum cortisol levels were within normal ranges, the circadian rhythm has
      completely disappeared. Free thyroxine and triiodothyronine levels were
      decreased. Adrenocorticotropin did not respond to corticotropin-releasing
      hormone, and urinary excretion of 17-hydroxycorticosteroids was not suppressed by
      dexamethasone. Abdominal computed tomography and 131I-Adosterol scintigraphy
      demonstrated a unilateral functioning mass in the left adrenal gland. The
      resected left adrenal mass was pathologically diagnosed as the rare condition of
      adrenocortical nodular hyperplasia.

PMID- 9630200
TI  - Liddle's syndrome in an elderly woman.
AB  - A 78-year-old woman with hypertension was hospitalized with acute bronchitis.
      However, she was also found to have hypernatremia, hypokalemia, and metabolic
      alkalosis. Detailed examination showed a low plasma renin activity and plasma
      aldosterone concentration. A provisional diagnosis of Liddle's syndrome was
      established and the patient was successfully treated with triamterene. Although
      Liddle's syndrome is generally considered an inherited hypertensive disease found
      in young people, a review of the literature indicated that muscle weakness is an
      important clinical finding in elderly patients with this disease. Liddle's
      syndrome should be considered in the differential diagnosis of hypertension even
      in elderly individuals.

PMID- 9630201
TI  - Symptomatic hypocalcemia in a patient with latent hypoparathyroidism and breast
      carcinoma with bone metastasis following administration of pamidronate.
AB  - Pamidronate is an effective drug used not only in patients with tumor-associated
      hypercalcemia, but also in normocalcemic patients with metastatic bone disease to
      relieve pains. We describe a 39-year-old normocalcemic patient with subclinical
      hypoparathyroidism and bone metastasis due to breast carcinoma. Following
      parenteral administration of 60 mg pamidronate, the corrected serum level of
      calcium decreased from 2.12 mmol/l (=8.9 mg/dl) to 1.42 mmol/l (5.7 mg/dl),
      accompanied with carpal pedal spasm. The present case indicates that the
      hypocalcemia due to latent hypoparathyroidism was compensated by extensive
      osteolysis due to bone metastasis, and that overt hypocalcemia may develop after
      intravenous administration of pamidronate in such a patient.

PMID- 9630202
TI  - Variant angina in isolated adrenocorticotropin deficiency, inappropriate
      vasopressin secretion and Hashimoto's thyroiditis.
AB  - We report a 62-year-old male patient who had variant angina and isolated
      adrenocorticotropic hormone (ACTH) deficiency. His serum sodium concentration was
      low and vasopressin was inappropriately high for the low plasma osmolality. Serum
      free thyroxine (FT4) was low and thyroid stimulating hormone (TSH) was high with
      positive anti-thyroperoxidase antibodies, compatible with Hashimoto's
      thyroiditis. Treatment with Amrodipine and hydrocortisone relieved chest symptoms
      and hyponatremia, and hypothyroidism was also normalized. It is suggested that
      coronary artery spasm may be related to cortisol deficiency and/or
      inappropriately high vasopressin secretion and that hypothyroidism was
      ameliorated because the reduced responsiveness to TSH returned to normal due to
      hydrocortisone supplement.

PMID- 9630203
TI  - Adrenocorticotropic hormone-secreting pheochromocytoma.
AB  - A 41-year-old female had pheochromocytoma which secreted adrenocorticotropic
      hormone (ACTH). She was admitted to our hospital because of weight loss and
      excessive sweating. Not only urinary metanephrine but also plasma ACTH was
      extremely high. An abdominal echogram showed a cystic tumor in the left adrenal
      gland. An abdominal magnetic resonance imaging scan showed a hyperintense T2
      weighted abnormality inside the tumor. Left adrenalectomy was done. The tumor
      consisted of benign pheochromocytoma cells diffusely stained with anti-ACTH
      antibody. The present case did not show any typical Cushingoid symptoms which are
      common in ACTH-secreting pheochromocytomas.

PMID- 9630204
TI  - Two familial mesothelioma cases with high concentrations of soluble cytokeratin
      19 fragment in pleural fluid.
AB  - We report two cases of diffuse malignant pleural mesothelioma occurring almost
      simultaneously in one family. Patient 1 was a 42-year-old Japanese man who had
      worked as an electrical engineer for 25 years. Patient 2, his mother, was 69
      years old. She lived for 10 years with patient 1 after he started his work, and
      also worked at a shipyard herself for 6 years. The concentrations of cytokeratin
      subunit 19 fragment (CYFRA 21-1) in pleural fluid of the two patients were 1,500
      ng/ml, and 1,200 ng/ml, respectively. Measurement of CYFRA 21-1 concentration in
      the pleural fluid may be a useful tool for a diagnosis of malignant mesothelioma.

PMID- 9630205
TI  - Adult T-cell leukemia-lymphoma successfully treated with 2-chlorodeoxyadenosine.
AB  - Adult T-cell leukemia-lymphoma (ATL) is resistant to currently available
      chemotherapy and has a poor prognosis. We describe here a patient with ATL
      successfully treated with 2-chlorodeoxyadenosine (2-CdA). A 75-year-old Japanese
      male with an acute type of ATL, who had become resistant to the initial cytotoxic
      chemotherapy, was treated with 2-CdA administered by continuous drip infusion of
      0.09 mg/kg/d for seven consecutive days in one month (one cycle). After three
      cycles of treatment, partial remission (PR) was achieved. Surprisingly, 249 days
      after the administration of 2-CdA, ATL cells completely disappeared from the
      peripheral blood. PR was maintained during 10 weeks until evidence of a new
      lymphadenopathy. No remarkable toxicity of 2-CdA occurred.

PMID- 9630206
TI  - Thymic carcinoma associated with a high serum level of interleukin 6 diagnosed
      through the evaluation for asymptomatic elevation of acute-phase reactants.
AB  - A case of thymic squamous cell carcinoma producing interleukin-6 (IL-6) is
      reported. C-reactive protein (CRP), white blood cell (WBC) count, and serum IL-6
      had been elevated, and normalized immediately after tumorectomy. IL-6 in the
      culture supernatant from the tumor was significantly elevated and the expression
      of IL-6 mRNA was demonstrated in the tumor by a reverse transcriptase polymerase
      chain reaction method. Immunohistochemical study demonstrated that tumor cells
      were stained positive with an anti-IL-6 antibody. IL-6 derived from the tumor
      cells reflected the increase CRP and WBC counts. This case suggested that
      asymptomatic elevation of acute-phase reactants might be clues for the diagnosis
      of an IL-6 producing tumor.

PMID- 9630207
TI  - Eosinophilic fasciitis complicated with peripheral polyneuropathy.
AB  - Peripheral polyneuropathy and the complication of eosinophilic fasciitis (EF) is
      rare; only 2 such cases have been described previously. A 40-year-old woman
      suffered from swelling of the extremities after strenuous exercise and complained
      of bilateral paresthesia on the soles of her feet. The diagnosis was EF according
      to clinical symptoms, peripheral eosinophilia, and histological examination of
      the fascia. Nerve conduction tests also revealed sensory disturbance as
      mononeuritis multiplex. After administration of prednisolone, the swelling and
      tenderness of the extremities improved immediately but the neuropathy lasted for
      6 months.

PMID- 9630208
TI  - Mixed connective tissue disease with severe pulmonary hypertension and extensive
      subcutaneous calcification.
AB  - The results of the autopsy of a 38-year-old female with mixed connective tissue
      disease who had suffered from painful subcutaneous calcification in her buttocks
      and extremities for 14 years and died from rapidly progressive pulmonary
      hypertension are reported. On autopsy, her heart and lungs revealed changes of
      severe pulmonary hypertension with intimal thickening and plexiform lesions in
      the small pulmonary arteries which had resulted in the collapse of both lungs and
      caused marked dilatation and hypertrophy of the right ventricle of the heart.
      Microscopic examinations of the subcutaneous calcified tissues indicated that the
      calcification may have been caused by repeated panniculitis.

PMID- 9630209
TI  - Vasculogenesis, angiogenesis, and growth factors: ephrins enter the fray at the
      border.

PMID- 9630210
TI  - Viral dynamics in HIV-1 infection.

PMID- 9630211
TI  - T cell responses and viral escape.

PMID- 9630212
TI  - Chemokine receptors: keys to AIDS pathogenesis?

PMID- 9630213
TI  - HIV entry and its inhibition.

PMID- 9630214
TI  - HIV-1 auxiliary proteins: making connections in a dying cell.

PMID- 9630215
TI  - Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear
      oxysterol receptor LXR alpha.
AB  - We demonstrate that mice lacking the oxysterol receptor, LXR alpha, lose their
      ability to respond normally to dietary cholesterol and are unable to tolerate any
      amount of cholesterol in excess of that which they synthesize de novo. When fed
      diets containing cholesterol, LXR alpha (-/-) mice fail to induce transcription
      of the gene encoding cholesterol 7alpha-hydroxylase (Cyp7a), the rate-limiting
      enzyme in bile acid synthesis. This defect is associated with a rapid
      accumulation of large amounts of cholesterol in the liver that eventually leads
      to impaired hepatic function. The regulation of several other crucial lipid
      metabolizing genes is also altered in LXR alpha (-/-) mice. These results
      demonstrate the existence of a physiologically significant feed-forward
      regulatory pathway for sterol metabolism and establish the role of LXR alpha as
      the major sensor of dietary cholesterol.

PMID- 9630216
TI  - Cyclooxygenase regulates angiogenesis induced by colon cancer cells.
AB  - To explore the role of cyclooxygenase (COX) in endothelial cell migration and
      angiogenesis, we have used two in vitro model systems involving coculture of
      endothelial cells with colon carcinoma cells. COX-2-overexpressing cells produce
      prostaglandins, proangiogenic factors, and stimulate both endothelial migration
      and tube formation, while control cells have little activity. The effect is
      inhibited by antibodies to combinations of angiogenic factors, by NS-398 (a
      selective COX-2 inhibitor), and by aspirin. NS-398 does not inhibit production of
      angiogenic factors or angiogenesis induced by COX-2-negative cells. Treatment of
      endothelial cells with aspirin or a COX-1 antisense oligonucleotide inhibits COX
      1 activity/expression and suppresses tube formation. Cyclooxygenase regulates
      colon carcinoma-induced angiogenesis by two mechanisms: COX-2 can modulate
      production of angiogenic factors by colon cancer cells, while COX-1 regulates
      angiogenesis in endothelial cells.

PMID- 9630217
TI  - Identification of a gene encoding a hyperpolarization-activated pacemaker channel
      of brain.
AB  - The generation of pacemaker activity in heart and brain is mediated by
      hyperpolarization-activated cation channels that are directly regulated by cyclic
      nucleotides. We previously cloned a novel member of the voltage-gated K channel
      family from mouse brain (mBCNG-1) that contained a carboxy-terminal cyclic
      nucleotide-binding domain (Santoro et al., 1997) and hence proposed it to be a
      candidate gene for pacemaker channels. Heterologous expression of mBCNG-1
      demonstrates that it does indeed code for a channel with properties
      indistinguishable from pacemaker channels in brain and similar to those in heart.
      Three additional mouse genes and two human genes closely related to mBCNG-1
      display unique patterns of mRNA expression in different tissues, including brain
      and heart, demonstrating that these channels constitute a widely expressed gene
      family.

PMID- 9630218
TI  - Sec6/8 complex is recruited to cell-cell contacts and specifies transport vesicle
      delivery to the basal-lateral membrane in epithelial cells.
AB  - In budding yeast, the Sec6/8p complex is essential for generating cell polarity
      by specifying vesicle delivery to the bud tip. We show that Sec6/8 homologs are
      components of a cytosolic, approximately 17S complex in nonpolarized MDCK
      epithelial cells. Upon initiation of calcium-dependent cell-cell adhesion,
      approximately 70% of Sec6/8 is rapidly (t(1/2) approximately 3-6 hr) recruited to
      sites of cell-cell contact. In streptolysin-O-permeabilized MDCK cells, Sec8
      antibodies inhibit delivery of LDL receptor to the basal-lateral membrane, but
      not p75NTR to the apical membrane. These results indicate that lateral membrane
      recruitment of the Sec6/8 complex is a consequence of cell-cell adhesion and is
      essential for the biogenesis of epithelial cell surface polarity.

PMID- 9630219
TI  - Molecular distinction and angiogenic interaction between embryonic arteries and
      veins revealed by ephrin-B2 and its receptor Eph-B4.
AB  - The vertebrate circulatory system is composed of arteries and veins. The
      functional and pathological differences between these vessels have been assumed
      to reflect physiological differences such as oxygenation and blood pressure. Here
      we show that ephrin-B2, an Eph family transmembrane ligand, marks arterial but
      not venous endothelial cells from the onset of angiogenesis. Conversely, Eph-B4,
      a receptor for ephrin-B2, marks veins but not arteries. ephrin-B2 knockout mice
      display defects in angiogenesis by both arteries and veins in the capillary
      networks of the head and yolk sac as well as in myocardial trabeculation. These
      results provide evidence that differences between arteries and veins are in part
      genetically determined and suggest that reciprocal signaling between these two
      types of vessels is crucial for morphogenesis of the capillary beds.

PMID- 9630220
TI  - FGF and Shh signals control dopaminergic and serotonergic cell fate in the
      anterior neural plate.
AB  - During development, distinct classes of neurons are specified in precise
      locations along the dorso-ventral and anterior-posterior axes of the neural tube.
      We provide evidence that intersections of Shh, which is expressed along the
      ventral neural tube, and FGF8, which is locally produced at the mid/hindbrain
      boundary and in the rostral forebrain, create induction sites for dopaminergic
      neurons in the midbrain and forebrain. The same intersection, when preceded by a
      third signal, FGF4, which is expressed in the primitive streak, defines an
      inductive center for hindbrain 5-HT neurons. These findings illustrate that cell
      patterning in the neural plate is a multistep process in which early inducers,
      which initially divide the neural plate into crude compartments, are replaced by
      multiple local organizing centers, which specify distinct neuronal cell types
      within these compartments.

PMID- 9630221
TI  - Wingless repression of Drosophila frizzled 2 expression shapes the Wingless
      morphogen gradient in the wing.
AB  - In Drosophila wing imaginal discs, the Wingless (Wg) protein acts as a morphogen,
      emanating from the dorsal/ventral (D/V) boundary of the disc to directly define
      cell identities along the D/V axis at short and long range. Here, we show that
      high levels of a Wg receptor, Drosophila frizzled 2 (Dfz2), stabilize Wg,
      allowing it to reach cells far from its site of synthesis. Wg signaling represses
      Dfz2 expression, creating a gradient of decreasing Wg stability moving toward the
      D/V boundary. This repression of Dfz2 is crucial for the normal shape of Wg
      morphogen gradient as well as the response of cells to the Wg signal. In contrast
      to other ligand-receptor relationships where the receptor limits diffusion of the
      ligand, Dfz2 broadens the range of Wg action by protecting it from degradation.

PMID- 9630222
TI  - The PHANTASTICA gene encodes a MYB transcription factor involved in growth and
      dorsoventrality of lateral organs in Antirrhinum.
AB  - The organs of a higher plant show two fundamental axes of asymmetry:
      proximodistal and dorsoventral. Dorsoventrality in leaves, bracts, and petal
      lobes of Antirrhinum majus requires activity of the PHANTASTICA (PHAN) gene.
      Conditional mutants revealed that PHAN is also required for earlier elaboration
      of the proximodistal axis. PHAN was isolated and shown to encode a MYB
      transcription factor homolog. PHAN mRNA is first detected in organ initials
      before primordium initiation. The structure and expression pattern of PHAN,
      together with its requirement in two key features of organ development, are
      consistent with a role in specifying lateral organ identity as distinct from that
      of the stem or meristem. PHAN also appears to maintain meristem activity in a non
      cell-autonomous manner.

PMID- 9630223
TI  - A mutant Drosophila homolog of mammalian Clock disrupts circadian rhythms and
      transcription of period and timeless.
AB  - We report the identification, characterization, and cloning of a novel Drosophila
      circadian rhythm gene, dClock. The mutant, initially called Jrk, manifests
      dominant effects: heterozygous flies have a period alteration and half are
      arrhythmic, while homozygous flies are uniformly arrhythmic. Furthermore, these
      flies express low levels of the two clock proteins, PERIOD (PER) and TIMELESS
      (TIM), due to low per and tim transcription. Mapping and cloning of the Jrk gene
      indicates that it encodes the Drosophila homolog of mouse Clock. The mutant
      phenotype results from a premature stop codon that eliminates much of the
      putative activation domain of this bHLH-PAS transcription factor, thus explaining
      the dominant features of Jrk. The remarkable sequence conservation strongly
      supports common clock components present in the common ancestor of Drosophila and
      mammals.

PMID- 9630224
TI  - CYCLE is a second bHLH-PAS clock protein essential for circadian rhythmicity and
      transcription of Drosophila period and timeless.
AB  - We report the identification, characterization, and cloning of another novel
      Drosophila clock gene, cycle (cyc). Homozygous cyc flies are completely
      arrhythmic. Heterozygous cyc/+ flies are rhythmic but have altered periods,
      indicating that the cyc locus has a dosage effect on period. The molecular
      circadian phenotype of homozygous cyc flies is like homozygous Clk flies
      presented in the accompanying paper: mutant flies have little or no transcription
      of the per and tim genes. Cloning of the gene indicates that it also encodes a
      bHLH-PAS transcription factor and is a Drosophila homolog of the human protein
      BMAL1. cyc is a nonsense mutation, consistent with its strong loss-of-function
      phenotype. We propose that the CYC:CLK heterodimer binds to per and tim E boxes
      and makes a major contribution to the circadian transcription of Drosophila clock
      genes.

PMID- 9630225
TI  - S. typhimurium encodes an activator of Rho GTPases that induces membrane ruffling
      and nuclear responses in host cells.
AB  - S. typhimurium stimulates signaling pathways leading to membrane ruffling, actin
      cytoskeleton rearrangements, and nuclear responses. The stimulation requires a
      protein secretion system (type III) that translocates bacterial proteins into the
      host cell. We show that SopE, a substrate of this secretion system, stimulates
      cytoskeletal reorganization and JNK activation in a CDC42- and Rac-1-dependent
      manner. A lambda gt11 cDNA library screen for proteins that interact with SopE
      identified Rac-1 and CDC42. Furthermore, purified SopE was shown to stimulate
      GDP/GTP nucleotide exchange in several Rho GTPases in vitro, including Rac-1 and
      CDC42. These findings establish a paradigm for microbial stimulation of cellular
      responses in which the pathogen induces signaling events by directly engaging the
      signaling machinery within the host cell.

PMID- 9630226
TI  - Crystal structure of a tyrosine phosphorylated STAT-1 dimer bound to DNA.
AB  - The crystal structure of the DNA complex of a STAT-1 homodimer has been
      determined at 2.9 A resolution. STAT-1 utilizes a DNA-binding domain with an
      immunoglobulin fold, similar to that of NFkappaB and the p53 tumor suppressor
      protein. The STAT-1 dimer forms a contiguous C-shaped clamp around DNA that is
      stabilized by reciprocal and highly specific interactions between the SH2 domain
      of one monomer and the C-terminal segment, phosphorylated on tyrosine, of the
      other. The phosphotyrosine-binding site of the SH2 domain in each monomer is
      coupled structurally to the DNA-binding domain, suggesting a potential role for
      the SH2-phosphotyrosine interaction in the stabilization of DNA interacting
      elements.

PMID- 9630227
TI  - Stat5a and Stat5b proteins have essential and nonessential, or redundant, roles
      in cytokine responses.
AB  - A variety of cytokines mediate the activation of Janus protein tyrosine kinases
      (Jaks). The Jaks then phosphorylate cellular substrates, including members of the
      signal transducers and activators of transcription (Stat) family of transcription
      factors. Among the Stats, the two highly related proteins, Stat5a and Stat5b, are
      activated by a variety of cytokines. To assess the role of the Stat5 proteins,
      mutant mice were derived that have the genes deleted individually or together.
      The phenotypes of the mice demonstrate an essential, and often redundant, role
      for the two Stat5 proteins in a spectrum of physiological responses associated
      with growth hormone and prolactin. Conversely, the responses to a variety of
      cytokines that activate the Stat5 proteins, including erythropoietin, are largely
      unaffected.

PMID- 9630228
TI  - Intramolecular masking of nuclear import signal on NF-AT4 by casein kinase I and
      MEKK1.
AB  - T cell activation requires the import of NF-AT transcription factors to the
      nucleus, a process promoted by calcineurin-dependent dephosphorylation and
      inhibited by poorly understood protein kinases. Here, we report the
      identification of two protein kinases that oppose NF-AT4 nuclear import. Casein
      kinase Ialpha directly binds and phosphorylates NF-AT4, resulting in the
      inhibiton of NF-AT4 nuclear translocation. MEKK1 indirectly suppresses NF-AT4
      nuclear import by stabilizing the interaction between NF-AT4 and CKIalpha.
      CKIalpha thus acts to establish an intramolecular masking of the nuclear location
      signal on NF-AT4, while MEKK1 augments this mechanism, and may further provide a
      link to signal transduction pathways regulating NF-AT4.

PMID- 9630229
TI  - Prefoldin, a chaperone that delivers unfolded proteins to cytosolic chaperonin.
AB  - We describe the discovery of a heterohexameric chaperone protein, prefoldin,
      based on its ability to capture unfolded actin. Prefoldin binds specifically to
      cytosolic chaperonin (c-cpn) and transfers target proteins to it. Deletion of the
      gene encoding a prefoldin subunit in S. cerevisiae results in a phenotype similar
      to those found when c-cpn is mutated, namely impaired functions of the actin and
      tubulin-based cytoskeleton. Consistent with prefoldin having a general role in
      chaperonin-mediated folding, we identify homologs in archaea, which have a class
      II chaperonin but contain neither actin nor tubulin. We show that by directing
      target proteins to chaperonin, prefoldin promotes folding in an environment in
      which there are many competing pathways for nonnative proteins.

PMID- 9630230
TI  - HTLV-I Tax protein binds to MEKK1 to stimulate IkappaB kinase activity and NF
      kappaB activation.
AB  - NF-kappaB, a key regulator of the cellular inflammatory and immune response, is
      activated by the HTLV-I transforming and transactivating protein Tax. We show
      that Tax binds to the amino terminus of the protein kinase MEKK1, a component of
      an IkappaB kinase complex, and stimulates MEKK1 kinase activity. Tax expression
      increases the activity of IkappaB kinase beta (IKKbeta) to enhance
      phosphorylation of serine residues in IkappaB alpha that lead to its degradation.
      Dominant negative mutants of both IKKbeta and MEKK1 prevent Tax activation of the
      NF-kappaB pathway. Furthermore, recombinant MEKK1 stimulates IKKbeta
      phosphorylation of IkappaB alpha. Thus, Tax-mediated increases in NF-kappaB
      nuclear translocation result from direct interactions of Tax and MEKK1 leading to
      enhanced IKKbeta phosphorylation of IkappaB alpha.

PMID- 9630231
TI  - Partial V(D)J recombination activity leads to Omenn syndrome.
AB  - Genomic rearrangement of the antigen receptor loci is initiated by the two
      lymphoid-specific proteins Rag-1 and Rag-2. Null mutations in either of the two
      proteins abrogate initiation of V(D)J recombination and cause severe combined
      immunodeficiency with complete absence of mature B and T lymphocytes. We report
      here that patients with Omenn syndrome, a severe immunodeficiency characterized
      by the presence of activated, anergic, oligoclonal T cells, hypereosinophilia,
      and high IgE levels, bear missense mutations in either the Rag-1 or Rag-2 genes
      that result in partial activity of the two proteins. Two of the amino acid
      substitutions map within the Rag-1 homeodomain and decrease DNA binding activity,
      while three others lower the efficiency of Rag-1/Rag-2 interaction. These
      findings provide evidence to indicate that the immunodeficiency manifested in
      patients with Omenn syndrome arises from mutations that decrease the efficiency
      of V(D)J recombination.

PMID- 9630232
TI  - IHF modulation of Tn10 transposition: sensory transduction of supercoiling status
      via a proposed protein/DNA molecular spring.
AB  - Architectural protein IHF modulates Tn10 transposition in vitro. IHF stimulates
      transposon excision. Also, separately, IHF forces transposon end/target DNA
      interactions into a constrained pathway, "channeling," that yields only unknotted
      intratransposon inversion circles. Negative supercoiling influences both effects,
      differently. We infer that IHF is an architectural catalyst: it promotes initial
      transpososome assembly and is then ejected from the transpososome. IHF then
      rebinds, altering transpososome conformation to promote channeling. We also infer
      that the developing transpososome is a molecular spring: DNA provides basic
      elasticity; a conformational change in transposase provides force; and IHF and/or
      supercoiling provide conformational inputs. In vivo, IHF is a sensory transducer
      of chromosomal supercoiling status: with supercoiling absent, IHF is
      "supercoiling relief factor"; with supercoiling present, stimulation and
      channeling comprise a homeostatic pair such that modest changes in chromosome
      condition strongly influence transpositional outcome.

PMID- 9630233
TI  - The hereditary ataxias.
AB  - Efforts to classify the hereditary ataxias by their clinical and
      neuropathological phenotypes are troubled by excessive heterogeneity. Linkage
      analysis opened the door to a new approach with the methods of molecular biology.
      The classic form of autosomal recessive ataxia, Friedreich's ataxia (FA), is now
      known to be due to an intronic expansion of a guanine-adenine-adenine (GAA)
      trinucleotide repeat. The autosomal dominant ataxias such as olivopontocerebellar
      atrophy (OPCA), familial cortical cerebellar atrophy (FCCA), and Machado-Joseph
      disease (MJD) have been renamed the spinocerebellar ataxias (SCA). Specific gene
      loci are indicated as SCA-1, SCA-2, SCA-3, SCA-4, SCA-5, SCA-6, and SCA-7. In 5
      of them (SCA-1, SCA-2, SCA-3, SCA-6, and SCA-7), expanded cytosine-adenine
      guanine (CAG)-trinucleotide repeats and their abnormal gene products cause the
      ataxic condition. The most common underlying loci for olivopontocerebellar
      atrophy (OPCA) are SCA-1 and SCA-2, although other genotypes may be added in the
      future. A major recent advance was the identification of the gene for SCA-3 and
      MJD, and the high prevalence of this form of autosomal dominant ataxia. In FA and
      the SCA with expanded CAG-trinucleotide repeats, clinical and neuropathological
      severity are inversely correlated with the lengths of the repeats. Anticipation
      in the dominant ataxias can now be explained by lengthening of the repeats in
      successive generations. Progress is being made in the understanding of the
      pathogenesis of FA and SCA as the absent or mutated gene products are studied by
      immunocytochemistry in human and transgenic murine brain tissue. In FA, frataxin
      is diminished or absent, and an excess of mitochondrial iron may cause the
      illness of the nervous system and the heart. In SCA-3, abnormal ataxin-3 is
      aggregated in neuronal nuclei, and in SCA-6, a mutated alpha1A-calcium channel
      protein is the likely cause of abnormal calcium channel function in Purkinje
      cells and in the death of these neurons.

PMID- 9630234
TI  - Sustained hypoxia-ischemia results in reactive nitrogen and oxygen species
      production and injury in the premature fetal rabbit brain.
AB  - Free radical-mediated injury is implicated in hypoxic-ischemic encephalopathy
      observed in neonates. We investigated in utero free radical production and injury
      following hypoxia-ischemia to premature fetal brain utilizing a rabbit model of
      acute placental insufficiency. Pregnant rabbits at 29 days gestation were
      randomized to uterine ischemia for 50 minutes (min) (hypoxia) or nonischemic
      controls. Fetal brains were obtained immediately after ischemia for oxidative and
      acute-injury markers or 24 hours (h) post-ischemia for histopathology.
      Nitrotyrosine formation, a marker of NO-derived species such as peroxynitrite,
      was observed only in hypoxic brains. Hypoxia resulted in a significant increase
      in nitrogen oxides, lipid peroxidation, and protein oxidation, with a concomitant
      decrease in total antioxidant capacity, compared with controls. Peroxynitrite
      addition to brain homogenate increased nitrogen oxides linearly (1:1), although
      protein carbonyls were unchanged. Concomitantly, in vitro cortical and
      hippocampal cell viability and ATP levels decreased, with an increase in brain
      edema in hypoxic brains. Fetuses delivered 24 h post-ischemia had increased
      hippocampal nuclear karyorrhexis on histology compared with controls. Antioxidant
      administration (ascorbic acid and Trolox) intraperitoneally ameliorated changes
      in cellular viability and brain edema. Acute fetal hypoxia-ischemia without
      reoxygenation results in increased nitrogen and oxygen free radical production
      that may cause brain injury. The merits of the described model are discussed.

PMID- 9630235
TI  - Expression of two glutamate transporters, GLAST and EAAT4, in the human
      cerebellum: their correlation in development and neonatal hypoxic-ischemic
      damage.
AB  - Normal development and hypoxic-ischemic changes of glutamate-aspartate
      transporters (GLAST) and excitatory amino acid transporter type 4 (EAAT4) were
      demonstrated in the human cerebellum. GLAST-immunoreactive Bergmann's glia and
      EAAT4-positive Purkinje cells showed a specific distribution and localization,
      and developed with age in the molecular and Purkinje cell layers. The dendrites
      and cell bodies of Purkinje cells, which showed EAAT4 immunoreactivity, were
      ensheathed by GLAST processes. In neonatal hypoxic-ischemic encephalopathy (HIE),
      GLAST immunoreactivity decreased in the molecular layer and increased in the
      inner granule cell layer at an early stage, and markedly increased in the
      Purkinje and inner granule cell layers at a late stage. EAAT4 immunoreactivity
      decreased with post-ischemic changes of Purkinje cells. GLAST reactivity changed
      more rapidly than EAAT4 in cases of HIE. These changes of GLAST and EAAT4 may be
      closely related to the vulnerability of Purkinje cells in hypoxia-ischemia. The
      glutamate transporter of Bergmann glia may play a more important role in the
      regulation of the extracellular glutamate concentration in hypoxia and/or
      ischemia.

PMID- 9630236
TI  - Intraventricular injection of human immunodeficiency virus type 1 (HIV-1) tat
      protein causes inflammation, gliosis, apoptosis, and ventricular enlargement.
AB  - To determine the role of the Tat protein of the human immunodeficiency virus type
      1 (HIV-1) in the pathogenesis of HIV-1 associated dementia, recombinant Tat was
      injected intraventricularly as a single or repeated dose into male Sprague-Dawley
      rats. Histopathological evaluation showed an initial infiltration of neutrophils
      one day after Tat injection, followed by macrophages and lymphocytes by 7 days.
      Tat-injected brains also exhibited astrocytosis, apoptotic cells, and ventricular
      enlargement 7 days following the last injection. Nuclear magnetic resonance
      spectroscopic analysis of tissue extracts of hippocampi from Tat-injected rats
      showed a decrease in the glutamate/g aminobutyric acid ratio. We conclude that
      the transient extracellular exposure of the central nervous system to Tat protein
      of HIV can cause a cascade of events leading to the influx of inflammatory cells,
      glial cell activation, and neurotoxicity.

PMID- 9630237
TI  - Intracellular calcium parallels motoneuron degeneration in SOD-1 mutant mice.
AB  - Transgenic mice with Cu,Zn superoxide dismutase (SOD-1) mutations provide a
      unique model to examine altered Ca homeostasis in selectively vulnerable and
      resistant motoneurons. In degenerating spinal motoneurons of G93 A SOD-1 mice,
      developing vacuoles were filled with calcium, while calcium was gradually
      depleted from the cytoplasm and intact mitochondria. In oculomotor neurons, no
      degenerative changes, vacuolization, or increased calcium were noted. Motor axon
      terminals of interosseus muscle gradually degenerated and intracellular calcium
      was depleted. Oculomotor terminals of mutant SOD-1 mice were smaller and
      exhibited no degenerative changes, but did exhibit unique membrane-enclosed
      organelles containing calcium. Spinal motoneurons of SOD-1 mice were shown to
      have fewer calcium binding proteins, such as parvalbumin, compared with
      oculomotor neurons. These data suggest that the SOD-1 mutation is associated with
      impaired calcium homeostasis in motoneurons in vivo, with increased likelihood of
      degeneration associated with higher levels of intracellular calcium and lower to
      absent levels of calbindin-D28K and/or parvalbumin, and decreased likelihood of
      degeneration associated with minimally changed calcium and ample calbindin-D28K
      and/or parvalbumin.

PMID- 9630238
TI  - The neuropathology of a chromosome 17-linked autosomal dominant parkinsonism and
      dementia ("pallido-ponto-nigral degeneration").
AB  - A group of similar autosomal dominant hereditary neurodegenerative disorders have
      been linked to chromosome 17 in thirteen kindreds. One of these disorders, known
      as pallido-ponto-nigral degeneration (PPND), is characterized by extensive
      degeneration of the globus pallidus and substantia nigra as well as accumulation
      of abnormally phosphorylated tau proteins. The authors now present comprehensive
      data on the cellular and molecular pathology of PPND, allowing its classification
      among chromosome 17-linked neurodegenerative disorders as well as its
      classification among sporadic and other familial tauopathies. First, we showed
      that PPND is characterized by abundant ballooned neurons in neocortical and
      subcortical regions as well as by tau-rich inclusions in the cytoplasm of neurons
      and oligodendroglia morphologically similar to those seen in corticobasal
      degeneration (CBD), but in a distribution pattern resembling progressive
      supranuclear palsy (PSP). Second, we demonstrated that antibodies to
      phosphorylation-independent (Alz50, 133, 304, Tau-2, T-46) as well as
      phosphorylation-dependent (AT8, PHF-6, 12E8, PHF-1, T3P, pS422) epitopes in human
      tau proteins stain these glial and neuronal inclusions as intensely as they stain
      CBD or PSP inclusions. Third, we probed PPND brain by Western blots using some of
      the same anti-tau antibodies to reveal 2 tau immunobands with molecular weights
      of 69 kD and 64 kD in gray and white matter extracts, as reported for both PSP
      and CBD. Finally, electron microscopy showed that these abnormal tau proteins
      formed flat twisted ribbons with a maximum diameter of 20 nanometers (nm) and a
      periodicity of about 200 nm, resembling those reported in CBD. Based on this, we
      conclude that PPND is a hereditary neurodegenerative disorder characterized by
      neuronal and glial tau-rich inclusions formed from aggregated filaments and
      hyperphosphorylated tau proteins and, hence, can be subcategorized into the
      tauopathy group of chromosome 17-linked neurodegenerative disorders. Further,
      since the morphologic and biochemical lesions of PPND overlap with those seen in
      sporadic CBD and PSP, we speculate that these disorders share common pathogenetic
      mechanisms.

PMID- 9630239
TI  - Apoptotic cells are present in the CNS throughout acute and chronic-progressive
      EAE in the absence of clinical recovery.
AB  - Experimental allergic encephalomyelitis (EAE) is an autoimmune, demyelinating
      disorder of the central nervous system induced in susceptible animals as a model
      for the human disease multiple sclerosis. Antibodies against the leukocyte
      adhesion molecule alpha4 integrin have been shown to prevent and reverse acute
      and chronic EAE of the guinea pig. The results presented in this paper implicate
      apoptosis as the mechanism of reversal of EAE following treatment with anti
      alpha4 integrin antibody. Apoptotic cells were observed in the central nervous
      system (CNS) throughout chronic-progressive EAE of the guinea pig in the absence
      of clinical recovery. Many of the apoptotic cells were identified as T cells
      using immunohistochemistry. Similarly, apoptotic cells were present in the CNS of
      animals during anti-alpha4 integrin-mediated recovery from acute and chronic
      disease. Therefore, anti-alpha4 integrin-mediated recovery from EAE is due to the
      prevention of the influx of new inflammatory cells into the CNS that are required
      to replace those undergoing apoptosis.

PMID- 9630240
TI  - Increased hippocampal AMPA and NMDA receptor subunit immunoreactivity in temporal
      lobe epilepsy patients.
AB  - This study determined if hippocampal AMPA and NMDA subunit immunoreactivity (IR)
      in temporal lobe epilepsy patients was increased compared with nonseizure
      autopsies. Hippocampi from hippocampal sclerosis patients (HS; n = 26) and
      nonsclerosis cases (non-HS: n = 12) were compared with autopsies (n = 6) and
      studied for GluR1, GluR2/3, NMDAR1, and NMDAR2 IR gray values (GV) along with
      fascia dentata and Ammon's horn neuron densities. Compared with autopsies, non-HS
      cases with similar neuron densities and HS patients with decreased neuron
      densities showed: (a) Increased GluR1 GVs in the fascia dentata molecular layer:
      (b) increased NMDAR1 GVs in the CA3-1 stratum radiatum and greater IR within
      pyramids; and (c) increased GluR2/3 and NMDAR2 GVs throughout all hippocampal
      subfields. Furthermore, HS patients showed that relative to the outer molecular
      layer: (a) GluR1 GV differences were decreased in the CA4/hilar region and CA1
      stratum radiatum compared with autopsies; and (b) NMDAR2 GV differences were
      increased in the inner molecular layer compared with non-HS cases. In temporal
      lobe seizure patients, these results indicate that AMPA and NMDA receptor subunit
      IR was increased in HS and non-HS hippocampi compared with nonseizure autopsies.
      In humans, these findings support the hypothesis that glutamate receptor subunits
      are increased in association with chronic temporal lobe seizures, which may
      enhance excitatory neurotransmission and seizure susceptibility.

PMID- 9630241
TI  - Fate of Schwann cells in CMT1A and HNPP: evidence for apoptosis.
AB  - The fate of Schwann cells in Charcot-Marie-Tooth (CMT) neuropathies was addressed
      in this study of nerve biopsies from patients with proven PMP22 duplications and
      deletions. In frozen sections, apoptotic nuclei were detected using the TUNEL
      method. In adjacent sections, anti-neurofilament 68kD antibody was used as an
      axonal marker, while the antibodies to NKH-1 and low-affinity nerve growth factor
      receptor P75NTR were used as Schwann cell markers. In addition, plastic sections
      were used to determine the densities of myelinated fibers and Schwann cell
      nuclei. In all biopsies from CMT1A, TUNEL-positive nuclei appeared in clusters.
      In adjacent sections, areas of TUNEL-positive nuclei matched with areas devoid of
      neurofilaments and NKH-1-positive Schwann cell silhouettes, suggesting that the
      apoptotic nuclei belonged to nonmyelinating Schwann cells. In addition,
      quantitative studies on plastic-embedded sections showed a significantly reduced
      number of total Schwann cells compared with controls, strongly favoring a loss of
      Schwann cell by apoptosis. In HNPP, the number of total Schwann cells was
      increased and a significant Schwann cell apoptosis was observed in only 2
      patients. Examination of plastic sections and teased nerve preparations from
      these cases suggested that the Schwann cell apoptosis might be related to the
      regenerative state of the nerve resulting from the process of sprout pruning. No
      strict correlation between p75NTR expression and apoptosis was found. These
      studies indicate that factors regulating Schwann cell number in early postnatal
      development continue to be important for Schwann cell survival throughout life.

PMID- 9630242
TI  - A new consensus report on biomarkers for the early antemortem diagnosis of
      Alzheimer disease: current status, relevance to drug discovery, and
      recommendations for future research.

PMID- 9630243
TI  - Transport of macromolecules between the nucleus and the cytoplasm.
AB  - Nuclear transport is an energy-dependent process mediated by saturable receptors.
      Import and export receptors are thought to recognize and bind to nuclear
      localization signals or nuclear export signals, respectively, in the transported
      molecules. The receptor-substrate interaction can be direct or mediated by an
      additional adapter protein. The transport receptors dock their cargoes to the
      nuclear pore complexes (NPC) and facilitate their translocation through the NPC.
      After delivering their cargoes, the receptors are recycled to initiate additional
      rounds of transport. Because a transport event for a cargo molecule is
      unidirectional, the transport receptors engage in asymmetric cycles of
      translocation across the NPC. The GTPase Ran acts as a molecular switch for
      receptor-cargo interaction and imparts directionality to the transport process.
      Recently, the combined use of different in vitro and in vivo approaches has led
      to the characterization of novel import and export signals and to the
      identification of the first nuclear import and export receptors.

PMID- 9630244
TI  - Modeling the tertiary interactions in the eukaryotic selenocysteine tRNA.
AB  - A novel three-dimensional model of tertiary interactions in the core region of
      the eukaryotic selenocysteine tRNA is proposed based on the analysis of available
      nucleotide sequences. The model features the 7/5 tRNA(Sec) secondary structure
      characterized by seven and five base pairs in the acceptor and T-stems,
      respectively, and four nucleotides in the connector region between the acceptor
      and D-stems. The model suggests a unique system of tertiary interactions in the
      area between the major groove of the D-stem and the first base pair of the extra
      arm that provides a rigid orientation of the extra arm and contributes to the
      overall stability of the molecule. The model is consistent with available
      experimental data on serylation, selenylation, and phosphorylation of different
      tRNA(Sec) mutants. The important similarity between the proposed model and the
      structure of the tRNA(Ser) is shown. Based on this similarity, the ability of
      some tRNA(Ser) mutants to be serylated, selenylated, and phosphorylated was
      evaluated and found to be in a good agreement with experimental data.

PMID- 9630246
TI  - Genetic analysis of the U5-PBS of a novel HIV-1 reveals multiple interactions
      between the tRNA and RNA genome required for initiation of reverse transcription.
AB  - A novel HIV-1 genome that stably utilizes tRNA(His) rather than tRNA(Lys,3) to
      initiate reverse transcription was used to study features for the interaction
      between the tRNA and viral RNA genome. In addition to a primer binding site (PBS)
      complementary to tRNA(His), this virus contains a six-nucleotide sequence in U5
      complementary to the anticodon-loop of tRNA(His) and three additional
      substitutions: U174-to-G, G181-to-A, and U200-to-C [HXB2(His-AC-GAC)]. Mutations
      in these three nucleotides resulted in viruses with three different genotypes:
      one group maintained a PBS complementary to tRNA(His) with restored G174A181C200
      or G174A181U200 configurations, one group reverted to a PBS complementary to
      tRNA(Lys,3), and one group contained two or more PBSs complementary to different
      tRNAs on the same viral genome. Characterization of a previously identified virus
      with additional C152-to-A and C160-to-U substitutions [HXB2(His-AC-A152U160-GAC)]
      revealed that this virus maintained a PBS complementary to tRNA(His), whereas a
      mutant HXB2(His-AC-U152A160-GAC) reverted after culture to contain dual PBS
      complementary to tRNA(Lys,3) and tRNA(His), respectively. Our results demonstrate
      that regions in U5 act in concert with the PBS to promote use of the tRNA primer
      for initiation of reverse transcription. These results are discussed with respect
      to structural models for the U5-PBS interactions with tRNA.

PMID- 9630245
TI  - A comprehensive biochemical and genetic analysis of the yeast U1 snRNP reveals
      five novel proteins.
AB  - The U1 snRNP is essential for recognition of the pre-mRNA 5'-splice site and the
      subsequent assembly of the spliceosome. Yeast U1 snRNP is considerably more
      complex than its metazoan counterpart, which suggests possible differences
      between yeast and metazoa in early splicing events. We have comprehensively
      analyzed the composition of yeast U1 snRNPs using a combination of biochemical,
      mass spectrometric, and genetic methods. We demonstrate the specific association
      of four novel U1 snRNP proteins, Snu71p, Snu65p, Nam8p, and Snu56p, that have no
      known metazoan homologues. A fifth protein, Npl3p, is an abundant cellular
      component that reproducibly co-purifies with the U1 snRNP, but its association is
      salt-sensitive. Therefore, we are unable to establish conclusively whether it
      binds specifically to the U1 snRNP. Interestingly, Nam8p and Npl3p were
      previously assigned functions in (pre-m)RNA-metabolism; however, so far, no
      association with U1 snRNP has been demonstrated or proposed. We also show that
      the yeast SmB protein is a U1 snRNP component. Yeast U1 snRNP therefore contains
      16 different proteins, including seven snRNP core proteins, three homologues of
      the metazoan U1 snRNP-specific proteins, and six yeast-specific U1 snRNP
      proteins. We have simultaneously continued the characterization of additional
      mutants isolated in a synthetic lethal (MUD) screen for genes that functionally
      cooperate with U1 snRNA. Consistent with the biochemical results, mud10, mud15,
      and mud16 are alleles of SNU56, NAM8, and SNU65, respectively. mud10 and mud15
      affect the in vivo splicing efficiency of noncanonical introns. Moreover, mud10p
      strongly affects the in vitro formation of splicing complexes, and extracts from
      the mud15 strain contain a U1 snRNP that migrates aberrantly on native gels.
      Finally, we show that Nam8p/Mud15p contributes to the stability of U1 snRNP.

PMID- 9630247
TI  - Autoantigenic properties of some protein subunits of catalytically active
      complexes of human ribonuclease P.
AB  - At least six proteins co-purify with human ribonuclease P (RNase P), a tRNA
      processing ribonucleoprotein. Two of these proteins, Rpp30 and Rpp38, are Th
      autoantigens. Recombinant Rpp30 and Rpp38 are also recognized by Th sera from
      systemic sclerosis patients. Two of the other proteins associated with RNase P,
      Rpp20 and Rpp40, do not cross-react with Th sera. Polyclonal antibodies raised
      against all four recombinant proteins recognize the corresponding proteins
      associated with RNase P and precipitate active holoenzyme. Catalytically active
      RNase P holoenzyme can be separated from the nucleolar and mitochondrial RNA
      processing endoribonuclease, RNase MRP, even though these two enzymes may share
      some subunits.

PMID- 9630248
TI  - Specific RNA self-cleavage in coconut cadang cadang viroid: potential for a role
      in rolling circle replication.
AB  - The rolling circle replication of the small, single-stranded viroid RNAs requires
      a specific processing reaction to produce monomeric RNAs that are ligated into
      the final circular form. For avocado sunblotch viroid, peach latent mosaic
      viroid, and chrysanthemum chlorotic mottle viroid, the hammerhead self-cleavage
      reaction is considered to provide this processing reaction. We have searched for
      a similar type of reaction in the 246-nt coconut cadang cadang viroid, the
      smallest viroid of the 24-member potato spindle tuber viroid (PSTV) group. RNA
      transcripts prepared from the cloned central or C domain of this viroid self
      cleaved specifically after denaturation with methylmercuric hydroxide followed by
      incubation in the presence of spermidine but in the absence of added magnesium
      ions. The unique cleavage site was located in the bottom strand of the C domain
      within a potential hairpin structure that is conserved within members of all
      three subgroups of the PSTV group of viroids.

PMID- 9630250
TI  - Human U19 intron-encoded snoRNA is processed from a long primary transcript that
      possesses little potential for protein coding.
AB  - While exons were originally defined as coding regions of split eukaryotic genes,
      introns have long been considered as mainly noncoding "genetic junk." However,
      recognition that a large number of small nucleolar RNAs (snoRNAs) are processed
      from introns of pre-mRNAs demonstrated that introns may also code for functional
      RNAs. Moreover, recent characterization of the mammalian UHG gene that encodes
      eight box C/D intronic snoRNAs suggested that some genes generate functional RNA
      products exclusively from their intron regions. In this study, we show that the
      human U19 box H/ACA snoRNA, which is encoded within the second intron of the U19H
      gene, represents the only functional RNA product generated from the long U19H
      primary transcript. Splicing of the U19H transcript, instead of giving rise to a
      defined RNA, produces a population of diverse U19H RNA molecules. Although the
      first three exons of the U19H gene are preserved in each processed U19H RNA, the
      3' half of the RNA is generated by a series of apparently random splicing events.
      Because the U19H RNA possesses limited potential for protein coding and shows a
      predominant nucleoplasmic localization, we suggest that the sole function of the
      U19H gene is to express the U19 intronic snoRNA. This suggests that, in marked
      contrast to our previous dogmatic view, genes generating functionally important
      RNAs exclusively from their intron regions are probably more frequent than has
      been anticipated.

PMID- 9630249
TI  - Regulated tissue-specific expression of antagonistic pre-mRNA splicing factors.
AB  - The SR proteins are essential metazoan pre-mRNA splicing factors that can also
      influence the selection of alternative 5' splice sites in a concentration
      dependent manner. Their activity in alternative splicing in vitro is antagonized
      by members of the hnRNP A/B family of proteins. The opposite effects of members
      of these two families of antagonistic splicing factors in vitro and upon
      overexpression in vivo suggest that changes in their relative levels may be a
      natural mechanism for the regulation of alternative splicing in vivo. One
      prediction of this model is that the ratios of these antagonists should vary in
      different cell types and in other situations in which cellular or viral
      transcripts are differentially spliced. We raised monoclonal antibodies specific
      for SF2/ASF and used them to measure the abundance of SF2/ASF protein and its
      isoforms, its phosphorylation state in vivo and during splicing in vitro, and its
      association with the spliceosome. SF2/ASF exists predominantly or exclusively in
      a highly phosphorylated state in vivo in all cell types examined, and
      unphosphorylated protein was not detectable. Unphosphorylated recombinant SF2/ASF
      becomes rapidly phosphorylated under splicing conditions in HeLa cell extracts
      and associates stably with one or more exons of beta-globin pre-mRNA. This
      interaction appears to persist through the splicing reaction and SF2/ASF remains
      bound to spliced mRNA. We compared the distribution of SF2/ASF to that of its
      antagonist, hnRNP A1, in different rat tissues and in immortal and transformed
      cell lines. We found that the protein levels of these antagonistic splicing
      factors vary naturally over a very wide range, supporting the notion that changes
      in the ratio of these proteins can affect alternative splicing of a variety of
      pre-mRNAs in vivo.

PMID- 9630251
TI  - Mechanistic analysis of RNA synthesis by RNA-dependent RNA polymerase from two
      promoters reveals similarities to DNA-dependent RNA polymerase.
AB  - The brome mosaic virus (BMV) RNA-dependent RNA polymerase (RdRp) directs template
      specific synthesis of (-)-strand genomic and (+)-strand subgenomic RNAs in vitro.
      Although the requirements for (-)-strand RNA synthesis have been characterized
      previously, the mechanism of subgenomic RNA synthesis has not. Mutational
      analysis of the subgenomic promoter revealed that the +1 cytidylate and the +2
      adenylate are important for RNA synthesis. Unlike (-)-strand RNA synthesis, which
      required only a high GTP concentration, subgenomic RNA synthesis required high
      concentrations of both GTP and UTP. Phylogenetic analysis of the sequences
      surrounding the initiation sites for subgenomic and genomic (+)-strand RNA
      synthesis in representative members of the alphavirus-like superfamily revealed
      that the +1 and +2 positions are highly conserved as a pyrimidine-adenylate. GDP
      and dinucleotide primers were able to more efficiently stimulate (-)-strand
      synthesis than subgenomic synthesis under conditions of limiting GTP.
      Oligonucleotide products of 6-, 7-, and 9-nt were synthesized and released by
      RdRp in 3-20-fold molar excess to full-length subgenomic RNA. Termination of RNA
      synthesis by RdRp was not induced by template sequence alone. Our
      characterization of the stepwise mechanism of subgenomic and (-)-strand RNA
      synthesis by RdRp permits comparisons to the mechanism of DNA-dependent RNA
      synthesis.

PMID- 9630252
TI  - Isoleucine:RNA sites with associated coding sequences.
AB  - An RNA family that binds isoleucine with Kd = 200-500 microM was repetitively
      isolated from a ribonucleotide transcript pool containing 50 randomized
      positions. The RNA site is specific, discriminating against branched side chains
      of different size (valine--one methylene smaller than isoleucine) by at least 1.3
      kcal/mol and against the shape (linear) of norleucine by 0.6 kcal/mol. The
      binding site was localized by sequence comparison, by synthesis of mutant and
      truncated active derivatives, and by chemical modification-interference. The
      binding site is small, no more than 10-12 nt, containing an asymmetric internal
      loop (6 over 2 nt) that includes the isoleucine codon AUU and a sequence of four
      G's, two of which are involved in G-U and G-C base pairs. Areas of U/G
      concentration like these may signal a hydrophobic RNA site.

PMID- 9630253
TI  - A dual-luciferase reporter system for studying recoding signals.
AB  - A new reporter system has been developed for measuring translation coupling
      efficiency of recoding mechanisms such as frameshifting or readthrough. A
      recoding test sequence is cloned in between the renilla and firefly luciferase
      reporter genes and the two luciferase activities are subsequently measured in the
      same tube. The normalized ratio of the two activities is proportional to the
      efficiency with which the ribosome "reads" the recoding signal making the
      transition from one open reading frame to the next. The internal control from
      measuring both activities provides a convenient and reliable assay of efficiency.
      This is the first enzymatic dual reporter assay suitable for in vitro
      translation. Translation signals can be tested in vivo and in vitro from a single
      construct, which allows an intimate comparison between the two systems. The assay
      is applicable for high throughput screening procedures. The dual-luciferase
      reporter system has been applied to in vivo and in vitro recoding of HIV-1 gag
      pol, MMTV gag-pro, MuLV gag-pol, and human antizyme.

PMID- 9630254
TI  - Models and need.

PMID- 9630255
TI  - The prevalence of Tourette syndrome in a mainstream school population.
AB  - The aim of this study was to ascertain accurately the prevalence of Tourette
      syndrome (TS) in a mainstream school population. All year 9 pupils (aged 13 to 14
      years) in a mainstream secondary school were investigated using a two-stage
      procedure. Standardized questionnaires were completed by parents, teachers, and
      pupils. Class observations were also carried out to identify tics. Those pupils
      identified as having tics underwent a semistructured interview to determine
      whether they had TS according to DSM-III-R criteria. Data were available from at
      least one source (parent, teacher, or self-reports) on 166 of the 167 pupils in
      the year. Five subjects were identified as having TS according to DSM-III-R
      criteria, yielding a prevalence estimate of 299 per 10,000 pupils in this age
      group. The results of this study suggest that TS in the community as a whole is
      more common and milder than those prevalence estimates and descriptions of the
      disorder based on TS encountered in secondary or tertiary health-care service
      settings.

PMID- 9630256
TI  - Relation between blindness due to retinopathy of prematurity and autistic
      spectrum disorders: a population-based study.
AB  - Children with blindness due to retinopathy of prematurity (ROP)--who are at
      greatly increased risk of cerebral damage--have been noted to have a high rate of
      autistic symptoms, but systematic controlled studies have been lacking. A
      controlled population-based study was performed; one group was blind due to ROP
      (N=27) and the other was congenitally blind due to hereditary retinal disease
      (N=14). Fifteen of the 27 children with ROP had autistic disorder. All these
      children were mentally retarded and about one-third of them had cerebral palsy.
      In the comparison group, two of the 14 children had autistic disorder. It is
      concluded that there is a strong association between ROP and autistic disorder.
      The association is most probably mediated by brain damage and is largely
      independent of the blindness per se.

PMID- 9630257
TI  - Visual outcome at 5 years of newborn infants at risk of cerebral visual
      impairment.
AB  - Visual development at 5 years of age was tested in a group of 39 children who had
      shown severe neonatal encephalopathy or perinatal brain lesions, documented by
      medical history, cranial ultrasound, or MRI. In all children, grating acuity was
      tested during the first 2 years of life. The assessment protocol at 5 years
      included various visual functions (grating and resolution acuity, visual field
      size, depth perception, optokinetic nystagmus, and ocular motility), and
      neurological and cognitive development. The majority of the children showed
      visual disorders of different type and degree, which were not due to
      ophthalmological abnormalities. Visual defects correlated well with the results
      of early visual assessment and of neuroimaging. Visual outcome could be predicted
      by grating acuity at 1 to 2 years in 27 of the 39 children, by neonatal cranial
      ultrasound in 26 of the 32 cases examined by this technique, and by later MRI in
      23 out of 27. Moreover, a significant correlation was found between visual,
      motor, and cognitive impairment.

PMID- 9630258
TI  - Assessment of preterm infants in the intensive-care unit to predict cerebral
      palsy and motor outcome at 6 years.
AB  - One hundred and fifty-three infants were assessed by a method specific to preterm
      infants and appropriate to the intensive-care nursery environment. The presence
      or absence of six atypical features (coarse jitters, dominant asymmetrical tonic
      neck reflex, paucity of movement, 'contradictory' development, hypotonia, or
      hypertonia) resulted in neonatal classification. There were 116 'usual' (an
      absence of atypical features with progressive development), 26 'unusual' (a
      transient occurrence of any atypical feature), and 11 'suspect' (dominance of one
      or more atypical features). At 6 years of age the motor subsystems of balance,
      coordination, fine and gross motor, and associated movements were assessed. Nine
      of 11 children with cerebral palsy had neonatal categories of 'suspect' (7) and
      'unusual' (2), of the remaining four other 'suspect' children, two failed two
      motor subsystems and two failed motor items. A 'usual' neonatal assessment
      predicted normal motor outcome for 72 of 116 (62%) whereas a 'suspect' assessment
      predicted major motor dysfunction for seven of 11 of the children.

PMID- 9630259
TI  - Effectiveness of speech intervention for phonological disorders: a randomized
      controlled trial.
AB  - Thirty children of preschool age with severe phonological disorders were randomly
      assigned to two treatment groups. Group 1 received treatment for 4 months
      followed by 4 months without treatment while group 2 underwent 4 months without
      treatment followed by 4 months of treatment. The outcome measures used were the
      Assessment of Phonological Processes-Revised (APP-R), the Goldman-Fristoe Test of
      Articulation (GFTA), the Percentage Consonants Correct (PCC), and Mean Length of
      Utterance (MLU). Group 1 showed significant differences on scores of phonological
      measures (APP-R, GFTA, and PCC) after the first 4 months of the study. At the 8
      month assessment point the measures for conversational speech intelligibility
      continued to be significantly different, with group 1 scores higher than those of
      group 2. The expressive language measure did not detect a difference between
      groups at any time; however group 1 scores were consistently higher than group 2
      scores.

PMID- 9630261
TI  - Are skinfold measurements suitable to compare body fat between children with
      spastic cerebral palsy and healthy controls?
AB  - The aim of this study was to assess whether percentage of body fat (BF) can be
      predicted adequately from skinfold measurements in comparative studies of
      children with spastic cerebral palsy (CP) and healthy control children. The
      deuterium dilution technique (D2O) was used as a reference method. In contrast
      with what was expected, %BF predicted from skinfold measurements was considerably
      lower than that determined by the D2O method in children with CP, whereas in the
      controls this was not seen. A proportionally large internal fat deposit and a
      different distribution of subcutaneous fat in children with CP may be responsible
      for this. It was concluded that skinfold measurements are not suitable for
      predicting %BF in comparative studies of children with CP and control children.
      For evaluation of diet- or exercise-related interventions in children with CP,
      the use of skinfold measurements seems to be justified. However, it may be more
      appropriate to use skinfold thicknesses without converting them to BF.

PMID- 9630260
TI  - MRI brain changes in subjects with Down syndrome with and without dementia.
AB  - Individuals with Down syndrome (DS), a disorder of known genetic etiology
      (trisomy of chromosome 21), exhibit several types of structural brain
      abnormalities that are detectable pathologically and by MRI. In addition, in
      middle age, individuals with DS develop histological and, in some cases, clinical
      features of Alzheimer's disease (AD). Abnormalities in MRI scans of 50 adults
      with DS, 11 of whom had clinical dementia, are described and compared with those
      of 23 cognitively normal, healthy subjects who were matched for age, sex, and
      race. Qualitative visual analogue scale (VAS) ratings on MRI hard copies for all
      subjects and computer-aided volume measures for a subsample of subjects were
      carried out. On VAS, subjects with DS had larger lateral ventricles, a higher
      frequency of posterior fossa arachnoid cysts/megacisterna magna and fewer scans
      rated as normal compared with controls. Quantitatively, total brain and gray
      matter volumes were reduced in DS, as were the volumes of the left hippocampus
      and amygdala; ventricle volumes were larger. Post hoc comparisons of subjects
      with DS with and without dementia revealed that on VAS the former had more
      generalized atrophy for age, mesial temporal shrinkage, and third ventricular
      enlargement. Similarly, total brain, left hippocampus, and left amygdala volumes
      were reduced quantitatively in subjects with DS with dementia, while ventricular
      volumes were increased.

PMID- 9630262
TI  - Behaviours caregivers use to determine pain in non-verbal, cognitively impaired
      individuals.
AB  - To create a checklist of behaviours that caregivers could use to determine pain
      in non-verbal individuals with mental retardation, primary caregivers were
      recruited by the Division of Neurology and interviewed using a semistructured
      interview. Caregivers of 20 individuals were asked to recall two instances of
      short, sharp pain and two of longer-lasting pain and describe the individual's
      behaviour. Transcribed interviews were reviewed by two of the authors and sets of
      non-overlapping items were developed. Average age of the 20 individuals was 14.5
      years (range 6 to 29 years) and language level averaged 10 months as scored by
      the MacArthur Communicative Development Inventory. All had mental retardation and
      18 had epilepsy and spastic quadriplegia or hemiparesis. Thirty-one behaviours
      were extracted from the interviews. The specific behaviours were often different
      from one child to another but the classes of behaviours (Vocal, Eating/Sleeping,
      Social/Personality, Facial expression of pain, Activity, Body and limbs, and
      Physiological) were common to almost all children. Reliability of using the
      checklist on interviews was very good (kappa=0.77). The checklist has excellent
      content validity and will be useful for caregivers of cognitively-impaired, non
      verbal individuals to report on pain behaviours. Further research is needed to
      additionally assess its validity and sensitivity.

PMID- 9630263
TI  - Development of perioral muscle activity during suckling in infants: a cross
      sectional and follow-up study.
AB  - The activity of the perioral muscles during breastfeeding in infants was
      investigated using EMGs. Fifty-six infants aged from 1 to 5 months were
      classified into five groups according to month of age in the cross-sectional
      study. Follow-up was carried out on 18 infants whose mean age was 2.5 months at
      the initial examination, and 4.8 months at the second. During suckling, EMGs were
      recorded unilaterally from the temporalis (TM), the masseter (MM), the
      orbicularis oris (OM), and the suprahyoid (SM) muscle groups. The activity of the
      SM increased significantly with age, while there was no appreciable increase in
      the activity of the TM, MM, and OM in either the cross-sectional study or the
      follow-up. However, total muscle activity was shown to increase significantly in
      both parts of the study. These findings suggest that the active tongue- and jaw
      lowering movement may play a primary role in increasing sucking strength during
      the suckle-feeding period in infants.

PMID- 9630264
TI  - Cerebral aqueduct stenosis presenting with limb pain.
AB  - Two children are reported with hydrocephalus and aqueduct stenosis who presented
      with back and limb pains. Neither had the classic symptoms of headache and
      vomiting. The children had enlarged heads and later developed ataxic gait and
      papilloedema. The cause of the pains is uncertain but similar symptoms have been
      reported in subjects with benign intracranial hypertension and may relate to
      spinal nerve root pouch distension. Operative ventricular drainage resulted in
      rapid improvement of all symptoms in both children.

PMID- 9630265
TI  - How much brain does a mind need? Scientific, clinical, and educational
      implications of ecological plasticity.

PMID- 9630266
TI  - 'Reflections on the hypothesis for the etiology of spastic cerebral palsy caused
      by the "vanishing twin" syndrome'.

PMID- 9630267
TI  - Imaging in liver transplantation.

PMID- 9630268
TI  - Pictorial review: Radiological diagnosis of duodenal abnormalities.
AB  - This article depicts the radiological findings of many common gastrointestinal
      entities. Specifically, examples of disease processes that affect the stomach,
      gall bladder, small intestine, pancreas and colon are shown. In most cases there
      is correlation between ultrasound, computed tomography (CT) and fluoroscopic
      imaging. The major emphasis of the article, however, is to demonstrate classic
      barium imaging of a large number of gastrointestinal disease processes.

PMID- 9630269
TI  - A phase contrast (PC) rephase/dephase sequence of magnetic resonance angiography
      (MRA): a new technique for imaging distal run-off in the pre-operative evaluation
      of peripheral vascular disease.
AB  - OBJECTIVE: To prospectively compare a 3-D phase contrast (PC) magnetic resonance
      angiography (MRA) sequence (rephase/dephase) with digital subtraction angiography
      (DSA) in pre-operative evaluation for femoropopliteal grafting in peripheral
      vascular disease. Assessment of distal run-off vessels and suggested siting of
      distal graft anastomosis to the above or below knee segment of the popliteal
      artery was made. METHODS: Twenty-two lower extremities booked for infra-inguinal
      vascular reconstruction were imaged pre-operatively using MRA and DSA. A PC
      rephase/dephase sequence which includes gradient motion refocusing (Siemens 1.0 T
      Magnetom Impact TR 50 ms, TE 14/14 ms and 15 degree flip angle) and 3-D MIP
      algorithm reconstruction was used to obtain the MR images. Standard techniques
      were used to obtain the DSA images, and the mean and median time between imaging
      modalities was one month. Blinded review by a consultant vascular radiologist
      scored nine vessel segments for each limb and assessed which popliteal arterial
      segment would be most suitable for distal anastomosis. RESULTS: The score from
      DSA and MRA agreed for 155/198 vessel segments (kappa 0.57) and the suggested
      siting for distal anastomosis agreed for 19/22 limbs (kappa 0.72). Eighteen limbs
      had surgery as planned (distal anastomosis to the above knee popliteal eight
      limbs, below knee popliteal 10 limbs). For three limbs the siting of the distal
      anastomosis suggested by DSA and MRA disagreed. The more accurate modality was
      proved for one of three limbs and showed MRA to be superior to DSA. CONCLUSION:
      Three-dimensional PC rephase/dephase MRA is a promising technique which compared
      well with DSA in the pre-operative assessment of distal run-off for
      femoropopliteal grafting.

PMID- 9630270
TI  - The role of hepatic arterial embolization in the treatment of spontaneous rupture
      of hepatocellular carcinoma.
AB  - Thirty-three patients presenting with spontaneous rupture of hepatocellular
      carcinomas (HCCs) were referred for emergency transcatheter arterial
      embolization. Blood was present in the ascitic fluid on abdominal paracentesis in
      all 33 patients. Seventeen patients underwent emergency computed tomography (CT).
      HCCs were demonstrated on CT in all 17 patients. Blood was detected in the
      peritoneal cavity or around the liver surface on CT in 15 patients (88.2%), one
      of whom also had active extravasation of the contrast medium into the peritoneal
      cavity. Vascular tumours were present in the hepatic angiograms prior to
      embolization in all 33 patients but extravasation of the contrast medium from the
      HCC was seen on angiography in only six patients (18.2%). Bleeding from the
      ruptured HCC was stopped at the end of the procedure in 32 patients who had
      undergone successful embolization. The overall median survival time was 9 weeks.
      The median survival time of patients with a serum total bilirubin level of 50
      micromol/l or below was 15 weeks, while that of patients with a serum total
      bilirubin level above 50 micromol/l was only 1 week, the difference being
      statistically significant. Embolization is therefore the treatment of choice in
      arresting life-threatening bleeding in ruptured HCC in patients with a serum
      total bilirubin level of 50 micromol/l or below, but the procedure is rarely
      effective in prolonging survival in patients with a serum total bilirubin above
      this critical level.

PMID- 9630271
TI  - Clinical risk associated with contrast angiography in metformin treated patients:
      a clinical review.
AB  - Recently, concern has been expressed about the hazards of lactic acidosis
      following the use of intravascular iodinated contrast agents in patients taking
      metformin. In response the Royal College of Radiologists have issued guidelines
      for the management of these patients. We have reviewed the reported cases of
      lactic acidosis and identified that in all cases underlying renal impairment
      existed. To examine this further we reviewed the notes of 33 in-patients
      receiving metformin who underwent contrast angiography in our hospital. Twenty
      nine patients had a normal serum creatinine prior to the procedure and none had a
      rise following angiography. Four patients had an abnormal serum creatinine prior
      to angiography, all four patients showed significant deterioration and all four
      patients died, two from unrelated causes and two from acute renal failure and
      acidosis. These data strongly highlight the hazards of intravascular contrast
      radiology in diabetic patients with pre-existing renal impairment. We have failed
      to find evidence in support of the Royal College of Radiologists recommendation;
      instead we recommend that in those patients taking metformin with evidence of
      renal impairment metformin should be stopped and diabetic control obtained using
      alternative therapy before proceeding with angiography. Patients with normal
      renal function taking metformin are not at risk of lactic acidosis following the
      use of iodinated contrast agents for angiography.

PMID- 9630272
TI  - The angiographic diagnosis of colonic carcinoma.
AB  - Carcinoma of the colon is a common cause of chronic iron deficiency anaemia in
      elderly patients and is conventionally diagnosed by either barium enema or
      colonoscopy. Occasionally these studies are inconclusive and individuals may
      proceed to further imaging, including angiography. Between December 1991 and
      October 1996, 337 patients were referred for visceral angiography to determine
      the cause of chronic gastrointestinal bleeding. In seven of these individuals
      (two males and five females with an age range of 65-74 years), all of whom had
      been investigated by barium enema and colonoscopy, both reported as showing no
      cause for bleeding, an arteriographic diagnosis of colonic carcinoma was made.
      Four of these demonstrated patchy areas of increased vascularity whilst three
      were predominantly hypovascular. Early venous drainage was seen in five. Marked
      irregularity and truncation of vasa rectae was present in six; more subtle
      irregularity was visible in one. The mural veins were irregular with or without
      truncation in five of the six patients in whom they were visualized. The marginal
      artery was angiographically involved in only two cases and in one of these the
      tumour was irresectable. It is important to recognize that a previous 'normal'
      colonoscopy and barium enema does not exclude a colonic neoplasm, even if
      advanced, and that this diagnosis may be made angiographically. Confusion with
      other pathologies, such as angiodysplasia, should be prevented by close scrutiny
      of vasa rectae at the site of arteriographic abnormality, which will usually
      demonstrate vascular irregularity and truncation highly suggestive of malignancy.

PMID- 9630273
TI  - Long-term follow-up of the antheor inferior vena cava filter.
AB  - The first long-term follow-up of the use of the Antheor inferior vena cava (IVC)
      filter is presented. Between December 1994 and December 1996, 20 Antheor IVC
      filters were inserted. Seven patients subsequently died and of the 13 patients
      remaining alive, 11 were available for long-term follow-up. One death was due to
      migration of the filter to the main pulmonary artery 6 weeks after insertion and
      because of this case, and other similar reports, the filter has now been
      withdrawn from clinical use. Of the 11 filters assessed at follow-up, three were
      fractured. One filter contained thrombus and one IVC was occluded. Our experience
      highlights the problem of central migration, but also shows a high incidence of
      filter fracture which has not previously been described with this design of
      filter.

PMID- 9630274
TI  - An evaluation of how MRI is used as a pre-operative screening investigation in
      patients with temporal lobe epilepsy.
AB  - AIMS: A retrospective analysis was carried out of how magnetic resonance imaging
      (MRI) is used as a pre-operative screening investigation in patients with a
      clinical diagnosis of medically intractable temporal lobe epilepsy (TLE). Up to
      65% of such patients are said to have hippocampal sclerosis (HS). MATERIALS AND
      METHODS: Forty-six patients in a 26-month period underwent MR examination on a
      1.5 T scanner according to a routine protocol. Each patient had coronal T1
      weighted and oblique coronal T2-weighted scans performed. Hippocampal volume was
      calculated from the T1-weighted images, the T2-weighted images being assessed for
      relative hippocampal signal intensity. Each individual patient's medical records
      were audited. RESULTS: Thirty per cent of patients in our study had a diagnosis
      of HS made on their MR scan. No patient had a diagnosis of HS made without prior
      clinical evidence of seizure lateralization. Sixty-eight per cent of patients
      with clinical evidence of a unilateral seizure focus had HS diagnosed by MR
      scanning. Forty-three per cent of patients did not have clinical evidence of an
      unilateral seizure focus. It was found that over 25% of patients referred to the
      unit did not fit the criteria of having medically intractable TLE. Nine per cent
      of patients had previously stated that they did not want epilepsy surgery.
      CONCLUSION: The lower than expected diagnostic rate of HS in this patient
      population reflects the broad criteria used in referring patients for imaging
      studies. This is likely to mirror the initial investigation of these patients
      outside specialist units where more extensive investigation prior to MRI is
      available. However, when MRI is used as an initial screening investigation, this
      study indicates that implementation of simple clinical criteria should
      significantly reduce the number of unnecessary scans.

PMID- 9630275
TI  - Orbital rhabdomyosarcoma--the radiological characteristics.
AB  - We reviewed computed tomography (CT) studies in 30 patients with histologically
      confirmed orbital rhabdomyosarcoma. There were 17 male and 13 female patients,
      mean age 8.8 years (median age 7 years, age range 1 month to 51 years). The
      tumour occupied the intra and extraconal compartments in 14 (47%) cases; it was
      solely extraconal in 11 (37%) and intraconal in five (16%). Within the orbit the
      upper inner quadrant was the most common site, 20 (67%) of the tumours lying in
      this region. More than one quadrant was involved in 16 (53%) cases. The epicentre
      of the tumour was in the eyelids of three (10%) patients. At presentation the
      mean size of the mass was 25 x 17 mm in long and short axis diameters,
      respectively. The tumours were of soft tissue density with moderately well
      defined margins and an irregular shape. They showed mild to moderate contrast
      enhancement. Calcification was seen in one case. Changes in the adjacent bone
      were seen in at least 12 (40%) patients. Intracranial extension was present in
      one (3%) patient and invasion of the paranasal sinuses was also seen in one (3%)
      patient. The intraorbital structures were displaced or encased by the tumour
      mass. The globe was displaced and distorted but not invaded by the tumour.
      Magnetic resonance imaging (MRI) studies were also reviewed in five patients. On
      T1-weighted images the tumour gave a similar signal to muscle but on T2-weighted
      images it gave a higher signal.

PMID- 9630276
TI  - Magnetic resonance imaging of acute intraosseous disc herniation.
AB  - Schmorl's nodes, the result of previous intraosseous disc herniation (IODH), are
      a common incidental finding on plain radiographs, computed tomography (CT) and
      magnetic resonance imaging (MRI). Acute IODH can, however, cause severe back
      pain, and the radiological features may also lead to inappropriate suspicion of
      malignancy or infection. We present eight cases of acute IODH in order to
      illustrate how the correct diagnosis can be made by MRI. In six cases isotope
      bone scintigraphy had been performed, demonstrating focal increased activity at
      the site of IODH. MRI can reinforce the concern about serious underlying
      pathology by the demonstration of marrow oedema, which may be localized around
      the disc herniation or extensive, extending throughout the vertebral body and
      into the pedicles. The key to the correct diagnosis is the recognition of the
      endplate defect and disc herniation. In three cases the diagnosis may have been
      possible from plain radiographs in which disc calcification visible on previous
      radiographs had migrated into an intraosseous location.

PMID- 9630277
TI  - Pyelocalyceal diverticula containing milk of calcium--CT diagnosis.
AB  - OBJECTIVE: To present the computed tomography (CT) findings of pyelocalyceal
      diverticula containing milk of calcium in seven patients. MATERIAL AND METHODS:
      Three patients were examined because of flank pain, one because a malignant
      lesion was suspected and the three others were examined for unrelated symptoms.
      Three repeated scans to the kidney area were performed in every patient: an
      unenhanced scan, post-contrast scan and a delayed scan. RESULTS: Unenhanced scans
      demonstrated an intraparenchymal round lesion with calcific material localized
      either at the inferior border or filling almost the entire cavity. On post
      contrast scans a contrast-fluid level appeared, with some enhancement of the
      clear fluid in the upper part of the cyst. A further rise in the contrast-fluid
      level or total opacification with a density identical to that of the collecting
      system was obtained on delayed scans. CONCLUSION: Pyelocalyceal diverticula
      containing milk of calcium present on CT as a partially calcified renal mass.
      Slight opacification soon after injection may be mistaken for enhancement
      arousing suspicion of a tumour. However, a delayed scan will demonstrate a
      densely opacified cyst filled with contrast from the collecting system which is
      virtually pathognomonic of the lesion.

PMID- 9630278
TI  - Radiographic detection of achalasia: diagnostic accuracy of videofluoroscopy.
AB  - AIMS: To retrospectively evaluate the accuracy of videofluoroscopy in the
      diagnosis of achalasia. MATERIALS AND METHODS: Videofluoroscopic studies of the
      oesophagus of 53 patients (25 males, 28 females; mean age, 49 years) with
      manometrically revealed diagnosis of achalasia were retrospectively evaluated.
      The videofluoroscopic examinations had been carried out with one swallow of low
      density barium suspension in the erect and up to three swallows in the prone
      oblique position. Videofluoroscopically, a diagnosis of achalasia was made in 31
      of the patients (58%) with manometrically proven achalasia, of whom only nine had
      oesophageal dilatation. Non-specific oesophageal motor abnormalities were
      diagnosed radiographically in 18 patients (34%) and a normal motility in four
      patients (8%). CONCLUSION: Videofluoroscopy is a valuable and sensitive technique
      for the detection of disordered oesophageal motility in achalasia.

PMID- 9630279
TI  - Isolated scaphotrapeziotrapezoid osteoarthritis: a possible radiographic marker
      of chronic scapholunate ligament disruption.
AB  - This study was undertaken to describe 'isolated' osteoarthritis of the
      scaphotrapeziotrapezoid articulation in six patients with chronic scapholunate
      ligament disruption. Each patient included for study had scapholunate ligament
      disruption with secondary dorsal intercalated segmental instability. Secondary
      volar tilt of the scaphoid appeared to be limited in each case by impaction and
      development of osteoarthritis at the scaphotrapeziotrapezoid articulation.
      Isolated osteoarthritis at the scaphotrapeziotrapezoid articulation may accompany
      chronic scapholunate ligament disruption, its identification should trigger a
      search for associated scapholunate ligament disruption in the absence of a known
      systemic arthropathy.

PMID- 9630280
TI  - Case report: CT appearance of capillary and cavernous lymphangiomatosis of the
      spleen in an adult.

PMID- 9630281
TI  - Case report: Percutaneous sialography.

PMID- 9630282
TI  - Case report: Magnetic resonance imaging in primary cervical lymphoma: the role in
      diagnosis and follow-up.

PMID- 9630283
TI  - Case report: A rare complication of Hickman line insertion.

PMID- 9630284
TI  - The radiological investigation of suspected lower limb deep vein thrombosis.

PMID- 9630286
TI  - MR of hepatic plexiform neurofibroma.

PMID- 9630285
TI  - Complications of sickle cell disease: intracranial aneurysms and their treatment.

PMID- 9630287
TI  - Current concepts in monitoring patients on antimalarials.

PMID- 9630288
TI  - Screening for diabetic retinopathy in rural and remote areas of Australia.

PMID- 9630289
TI  - The legal liability of health service providers. Final report: May 1997.

PMID- 9630290
TI  - Non-mydriatic fundus photography: a viable alternative to fundoscopy for
      identification of diabetic retinopathy in an Aboriginal population in rural
      Western Australia?
AB  - PURPOSE: To evaluate the Canon CR5-45NM non-mydriatic fundus camera (Canon,
      Kanagawa, Japan) for identifying retinopathy and the need for laser treatment in
      a population of Aboriginal patients with diabetes mellitus in rural Western
      Australia. METHODS: Diabetic Aboriginal patients were photographed through
      undilated pupils using a Canon CR5-45NM non-mydriatic fundus camera, after which
      ophthalmoscopy was performed using indirect ophthalmoscopy through dilated
      pupils. The examining ophthalmologist recorded the presence of retinopathy and
      the need for laser treatment. A proportion of patients were rephotographed
      through dilated pupils. Photographs were reviewed by a second ophthalmologist who
      evaluated the quality of the image, the presence of retinopathy and the need for
      laser treatment. Results of fundus photographs and ophthalmoscopy were compared.
      RESULTS: Three hundred and twenty-eight eyes in 164 Aboriginal patients were
      examined. The mean patient age was 48.2 years (range 16-81 years) and the mean
      duration of diabetes was 7.5 years (range 1-35 years). Seventy-four eyes (22.6%)
      were diagnosed with retinopathy using combined examination techniques, 44 (59.5%)
      of which were identified by ophthalmoscopy and 55 (74.3%) by photography. Thirty
      five eyes were deemed to need treatment, 18 (51.4%) of which were identified by
      ophthalmoscopy and 30 (85.7%) by photography. Kappa coefficient measurement for
      agreement for presence of retinopathy and need for referral was 0.41 and 0.53,
      respectively. Photograph quality was significantly improved following pupil
      dilation. CONCLUSIONS: The Canon CR5-45NM non-mydriatic fundus camera was
      relatively good at identifying diabetic retinopathy and could usefully be applied
      within a screening programme for treatable disease within this population.

PMID- 9630291
TI  - Screening for diabetic retinopathy using a non-mydriatic retinal camera in rural
      Victoria.
AB  - PURPOSE: To develop a screening programme for the early detection of diabetic
      retinopathy using non-mydriatic retinal photography. METHODS: A community based
      screening service was offered to all people with known diabetes mellitus in
      selected townships in the LaTrobe and Goulburn Valleys in Victoria. At the local
      examination centre, basic sociodemographic information was collected as well as
      details of previous use of eye care services for the early detection of diabetic
      retinopathy. The examination included visual acuity (VA), glycosylated
      haemoglobin level and Polaroid photographs of each fundus using a Canon CR5-45NM
      non-mydriatic retinal camera (Canon, Tochigiken, Japan). Dilating drops were not
      used. Photographs were subsequently reviewed and letters were sent to all
      participants (with copies to their general practitioners) with recommendations
      for appropriate follow up. RESULTS: A total of 1177 people with diabetes attended
      the screening service, which is estimated to be 40% of the total population with
      known diabetes in the study area. The mean age was 65 years (range 20-94 years);
      559 (48%) people reported not having a dilated fundus examination within the past
      2 years; 345 (29%) people had never had a dilated fundus examination. Of the 2354
      eyes, 2126 (90%) of the photographs were gradable. A total of 704 people (60%)
      had normal VA and no evidence of diabetic retinopathy, 209 people (18%) had
      diabetic retinopathy, 101 people (9%) had evidence of other fundus pathology, 42
      people (3%) had reduced acuity (< 6/18) in one or both eyes (with no fundus
      pathology evident) and 121 people (10%) had ungradable photographs in one or both
      eyes. CONCLUSIONS: The present study demonstrates the usefulness of a screening
      programme with non-mydriatic retinal photography as an adjunct to current eye
      care services for the early detection of diabetic retinopathy.

PMID- 9630292
TI  - Facial muscle spasms: an Australian study.
AB  - PURPOSE: A group of patients suffering from blepharospasm, hemifacial spasm and
      Meige's syndrome were surveyed to determine the delay from the onset of their
      condition until a correct diagnosis was reached, the attitudes of practitioners
      towards them and their condition, the effect of their condition on their
      lifestyle and the effects of different types of treatment on their conditions.
      METHODS: Questionnaires were offered to all patients with blepharospasm,
      hemifacial spasm and Meige's syndrome presenting to three ophthalmologists
      licensed to treat patients with botulinum toxin injections over a 12 month
      period. RESULTS: Patients consulted an average of 4.4 practitioners before a
      correct diagnosis was made and many waited a number of years before obtaining
      satisfactory treatment. Approximately two-thirds of all practitioners consulted
      were unaware of their condition. Ten per cent of patients reported a family
      history of similar conditions. Most patients received relief from their symptoms
      with treatment using injections of botulinum toxin. More than 55% of patients
      considered themselves to have psychological problems (usually relating to stress
      and trauma) that they associated with the onset of their condition. CONCLUSIONS:
      Facial muscle dystonias are rare and patient experiences suggest that they are
      poorly appreciated in the medical community. From the time they first see a
      practitioner with symptoms of facial dystonia, patients typically wait 2 years
      and see four practitioners before a correct diagnosis is made. Stress may be a
      factor in the symptomatic onset of this condition. Many patients describe pain as
      part of the presenting symptomatology. Botulinum toxin seems to be effective in
      the management of facial spasm.

PMID- 9630293
TI  - Visual outcome and progression of retinopathy after cataract surgery in diabetic
      patients.
AB  - PURPOSE: Diabetes mellitus is a major cause of visual impairment in developed
      countries through retinopathy and is frequently complicated by cataract
      formation. The present study examines the visual outcome of cataract surgery in
      diabetic pat ents. METHODS: A retrospective study was performed over a 26 month
      period in a general hospital eye clinic. Eighty-five consecutive diabetic
      patients who underwent cataract surgery were categorized according to their type
      of diabetes, duration and treatment, operative technique, pre-operative visual
      acuity (VA) and degree of retinopathy. Visual acuity and retinopathy status were
      recorded at a minimum of 4 months postoperatively. Factors affecting visual
      outcome and progression of retinopathy were then examined. RESULTS: Of the 107
      eyes of the 85 consecutive cases, 55 were without retinopathy (NR), 21 had
      background retinopathy (BDR), six had background retinopathy with macular oedema
      (BDR/MO), four had proliferative retinopathy and 12 cases had inadequate fundal
      view. In the NR and BDR groups, 90 and 81% of patients, respectively, had
      improved VA compared with 33% of patients with BDR/MO. Retinopathy progressed in
      50% of BDR/MO patients compared with progression in 9 and 19% of NR and BDR
      patients, respectively. CONCLUSION: The present study illustrates the poor visual
      outcome in patients with severe, untreated retinopathy, particularly maculopathy,
      following cataract surgery. Larger prospective studies are needed to better
      define risk groups and pre-operative treatment strategies.

PMID- 9630294
TI  - Diode laser cyclophotocoagulation: dose-standardized therapy in end-stage
      glaucoma.
AB  - BACKGROUND: Ciliary body ablation in end-stage glaucoma has been widely performed
      with cryotherapy and neodymium:yttrium aluminium garnet (Nd:YAG) laser, both
      techniques frequently involving considerable pain and postoperative inflammation,
      with an unpredictable final intraocular pressure (IOP) and a significant risk of
      phthisis. Diode laser cyclophotocoagulation (cyclodiode laser) has recently been
      introduced in an attempt to avoid some of these problems. METHODS: Thirty
      patients with uncontrolled IOP and advanced glaucoma were divided on clinical
      grounds into two groups and were treated with either a half or a full
      standardized dose of laser (40 x 1500 mW for 1500 ms) and monitored for IOP
      control, visual acuity, postoperative inflammation and phthisis. Success of IOP
      control was defined as IOP < 22 mmHg or a decrease in IOP of > 30%; preservation
      of visual acuity or control of pain in blind eyes was also assessed. RESULTS: A
      sustained lowering of IOP was achieved in 90% of patients, with a mean follow up
      of 10.4 months. For the full treatment cases (group A), mean (+/-SD) pre
      operative and postoperative IOP was 49.4 +/- 11.2 and 25.8 +/- 17.7 mmHg,
      respectively (a 48% reduction); 55% of patients achieved IOP < 22 mmHg and 68%
      gained an IOP reduction of > 30%. For the half-treatment cases (group B). the
      mean pre-operative and postoperative IOP was 29.4 +/- 4.3 and 18.9 +/- 5.7 mmHg,
      respectively (a 36% reduction); 63% of patients achieved IOP < 22 mmHg and 50%
      gained an IOP reduction of > 30%. Neovascular glaucoma was present in 60% of
      patients; the full-treatment subgroup of these patients achieved a mean lowering
      of IOP of 58%. Of 22 sighted eyes, 11 (50%) recorded no change in vision; seven
      (32%) eyes lost and four (18%) eyes gained vision; pain control was achieved in
      six of eight blind eyes (75%). There was no significant postoperative
      inflammation, one case of hypotony and no suggestion to date of sympathetic
      ophthalmia. CONCLUSION: Diode laser cyclophotocoagulation appears to be simple,
      safe and is frequently successful in the control of IOP in end-stage glaucoma.
      Optimum dosage parameters remain to be determined.

PMID- 9630295
TI  - Overview of studies on metabolic and vascular regulatory changes in early
      diabetic retinopathy.
AB  - The present review provides an overview of recent research describing functional
      changes to the retinal vasculature in very early diabetes. The research focuses
      on the streptozotocin rat model after 4-6 weeks of induced diabetes and describes
      functional changes to retinal blood flow, vascular control and retinal
      oxygenation, as well as a strong vasodilatory response to insulin in the retinal
      vasculature. The review raises the question of whether choroid dysfunction is
      also a feature of diabetic retinopathy.

PMID- 9630296
TI  - Complex motion stimuli localize higher-order visual processing in normal
      observers and in patients with parietal lesions.
AB  - The present paper illustrates how modern techniques applied in neuroscience can
      help us to understand the processing of visual information in the human brain
      and, in turn, how they can be helpful to characterize functional deficits in
      patients with cortical lesions. Based on theoretical considerations, motion
      stimuli are developed that require very specific operations to be performed by
      the visual system. Computational models explaining the processing of these
      'Fourier' and 'second-order' motion stimuli are characterized by increasing
      complexity. The same types of stimuli are used to map the distribution of
      cortical activity during motion perception by measuring the magnetic and
      electrical fields on the head surface. Clinical investigations of patients with
      lesions in the parietal cortex indicate specific deficits in the perception of
      such stimuli that can be related to the lesion sites.

PMID- 9630297
TI  - Allergic granulomas of the conjunctiva.

PMID- 9630298
TI  - Intravitreal cysticercosis: how did it get there?

PMID- 9630299
TI  - Congenital endophthalmitis following maternal shellfish ingestion.
AB  - PURPOSE: To highlight an unusual organism causing a unilateral endophthalmitis by
      transplacental spread. METHOD: We report a case of Plesiomonas shigelloides
      endophthalmitis, presenting in a newborn, with co-existing septicaemia and
      meningitis. There was a significant maternal history of diarrhoea associated with
      the ingestion of oysters 2 weeks prior to delivery. RESULT: The endophthalmitis
      was treated with parenteral antibiotics and topical mydriatics with complete
      resolution, although subsequent assessment of the affected eye suggests a poor
      visual outcome. CONCLUSION: Endophthalmitis in the newborn is an unusual clinical
      finding and usually presents with other manifestations of bacteraemia.
      Plesiomonas shigelloides is fortunately an infrequent cause of neonatal
      infection, but is associated with a high degree of morbidity and mortality. We
      postulate that this neonate acquired P. shigelloides via the transplacental
      route, and suggest that this organism be included in the list of 'other' causes
      of transplacental infection that has been abbreviated to 'O' in the acronym
      'TORCH'.

PMID- 9630300
TI  - Horner's syndrome resulting from a prolonged abnormal posture during a coma.
AB  - BACKGROUND: Horner's syndrome results from the impairment of the sympathetic
      nerve supply to the eye and orbit. Other nerve palsies from prolonged unchanged
      posture are well described, but Horner's syndrome following prolonged lateral
      flexion has only twice been seen previously and these cases were in association
      with anaesthesia. METHODS/RESULTS: A case is described of Horner's syndrome
      resulting from a prolonged period of unchanged posture from an alcohol-induced
      coma. A review of the anatomy of Horner's syndrome is presented. CONCLUSION: To
      my knowledge, this is the first reported case of Horner's syndrome resulting from
      a coma.

PMID- 9630301
TI  - Orbital osteoma in Gardner's syndrome.
AB  - PURPOSE: To report the association of an orbital osteoma with Gardner's syndrome
      (familial polyposis coli leading to carcinoma, multiple osteomas and skin and
      soft tissue tumours). METHOD: A review of patient records. RESULTS: A 29-year-old
      male with known Gardner's syndrome presented with long-standing right proptosis
      due to an osteoma of the medial wall and roof of the orbit. He had previously had
      prophylactic colectomy and one other osteoma of the skull excised. CONCLUSION:
      Although orbital osteoma in the setting of Gardner's syndrome is rare, it should
      be recognized as an association because of the importance of the intestinal
      polyposis, which leads to carcinoma if untreated.

PMID- 9630303
TI  - Bilateral arteritic central retinal artery occlusion in a Chinese patient.
AB  - PURPOSE: To report the first case of bilateral central retinal artery occlusion
      caused by giant cell arteritis in a Chinese patient. METHODS: We studied a
      Chinese patient who had a history of weight loss, calf claudication and
      sequential right and left central retinal artery occlusion. RESULTS: The
      erythrocyte sedimentation rate was greater than 150 mm/h. Temporal artery biopsy
      confirmed the diagnosis of giant cell arteritis. Systemic steroid prevented
      further visual loss in the second eye. CONCLUSIONS: We believe that this is the
      first report in literature on the ophthalmological presentation of giant cell
      arteritis in a Chinese patient. Giant cell arteritis as a cause of central
      retinal artery occlusion should always be on the list of differential diagnosis,
      as early diagnosis and treatment may help to salvage the first eye and prevent
      blindness from developing in the second eye.

PMID- 9630302
TI  - Inferior rectus rupture following blowout fracture.
AB  - BACKGROUND: Extra-ocular muscle rupture is uncommon, usually seen after
      penetrating trauma or surgery. It is a very rare cause of diplopia following
      blunt orbital trauma. METHODS: A patient who presented with no inferior rectus
      function after blunt orbital trauma is described. RESULTS: Computed tomography
      (CT) scans demonstrated a large orbital floor fracture and suggested that the
      inferior rectus muscle was ruptured. This was confirmed at operation. Despite
      anatomical repair, there was no postoperative improvement in ocular motility.
      CONCLUSIONS: Traumatic rupture of the inferior rectus is rare. Forced duction and
      force generation testing and CT are important in diagnosing ocular motility
      defects following orbital trauma.

PMID- 9630304
TI  - Immunoglobulin G crystalline keratopathy associated with monoclonal gammopathy.
AB  - PURPOSE: Two cases of corneal crystal deposition are reported, both caused by a
      benign monoclonal gammopathy METHODS: Similar corneal pathology is identified in
      these two patients, both of whom presented with visual acuities of 6/6 or better
      Consideration of possible causes involved biochemical and haematological testing
      and assessment. RESULTS: Potential for malignant transformation of monoclonal
      gammopathy was recognized, hence the need for ongoing haematological follow-up.
      CONCLUSION: Corneal crystals may be the initial presentation in a patient with
      monoclonal gammopathy, a rare, but significant, clinical finding.

PMID- 9630305
TI  - Association between anterior and posterior keratoconus.
AB  - BACKGROUND/METHODS: We studied a 53-year-old male patient, presenting with a
      history of reduced vision since childhood in the right eye and since birth in the
      left eye. RESULTS: Ocular examination revealed the presence of anterior
      keratoconus in the right eye and posterior keratoconus in the left eye.
      CONCLUSION: To our knowledge, co-occurrence of both varieties of keratoconus in
      the same patient has not been previously reported.

PMID- 9630306
TI  - Pyogenic granuloma of the cornea.
AB  - BACKGROUND: Ocular pyogenic granulomata are uncommon and are often associated
      with a chalazion or previous ocular and adnexal surgery The avascular nature of
      the cornea may explain the rarity of pyogenic granulomata at this site. We report
      on a case of corneal pyogenic granuloma following previous corneal surgery.
      METHODS: Ophthalmologists who had treated the patient previously were contacted
      and earlier clinical notes and histopathological examinations were reviewed. The
      clinical course following excision of the pyogenic granuloma is described, as are
      the histopathological findings. RESULTS: Histological examination confirmed the
      diagnosis of pyogenic granuloma. Excision was followed by a clinical recurrence
      at a different site with spontaneous resolution. CONCLUSIONS: Pyogenic
      granulomata of the cornea are rare. However, the present case illustrates the
      importance of considering benign inflammatory causes in the differential
      diagnosis of a corneal mass lesion so as to avoid unnecessarily aggressive
      intervention. To our knowledge, spontaneous resolution of a corneal pyogenic
      granuloma has not been previously described.

PMID- 9630307
TI  - Biotinylated platelets have an impaired response to agonists as evidenced by in
      vitro platelet aggregation tests.
AB  - Biotinylation of platelets, using a water soluble biotin analogue which reacts
      with primary amines, has been proposed to be a reliable technique for study of in
      vivo survival of platelets and their subpopulations. The information about the
      influence of this technique on platelet function has been limited. In the present
      work we studied the effect of in vitro biotinylation on platelet function and
      activation. Washed human platelets, at a concentration of 1 x 10(9)/L, were
      biotinylated with five different concentrations of sulfo-NHS-biotin or NHS-LC
      biotin, ranging from 0 to 5 mM. The degree of platelet activation during and
      after biotinylation was monitored by measuring the externalization of P-selectin,
      and the platelet function was evaluated by aggregometry. It was observed that
      biotinylated platelets, in a dose dependent manner, displayed an impaired
      aggregation response. A slight increase in platelet membrane P-selectin occurred
      during the labelling procedure.

PMID- 9630308
TI  - Degree of hypercoagulability and hyperfibrinolysis is related to organ failure
      and prognosis after burn trauma.
AB  - Severely burned patients often present a hypercoagulability situation. However,
      its magnitude, time course, and relationship with organ failure and outcome
      remains to be established. Forty-three patients were studied on the first and
      seventh day after burn for hypercoagulability and fibrinolysis parameters. A
      hypercoagulability and hyperfibrinolysis state was found the first day after burn
      demonstrated by high levels of activated factor VII (VIIa, p<0.01), thrombin
      antithrombin III complex (TAT, p<0.01), tissue plasminogen activator (t-PA,
      p<0.001) and D dimer (DD, p<0.01) and low levels of antithrombin III (ATIII,
      p<0.01), protein C (PC, p<0.01), plasminogen (PG, p<0.001) and alpha2 antiplasmin
      (AP, p<0.001). A paradoxical coexisting hypofibrinolysis was found as suggested
      by a low global fibrinolytic activity in the euglobulin plasma fraction fibrin
      plate assay (FA, p<0.01) and high levels of tissue plasminogen activator
      inhibitor type 1 (PAI-1, p<0.01). On day 7, a less marked hypercoagulability
      situation was found, with low ATIII (p<0.01) and PC (p<0.01), persisting the
      hypofibrinolytic situation observed on the first day. Non-survivors (NS) showed
      higher levels of VIIa (p<0.01), TAT (p<0.05) and t-PA (p<0.05), and lower levels
      of ATIII (p<0.05), PC (p<0.05) and AP (p<0.001) than survivors (S) on the first
      day. Also, there was a positive correlation of Marshall organ failure score with
      ATIII, (r2=0.49, p<0.001), PC, (r2=0.14, p<0.045) and PG levels, (r2=0.41,
      p<0.0003). Severely burned patients show a state of transient disseminated
      intravascular coagulation, related to the development of organ failure and
      outcome.

PMID- 9630309
TI  - Contribution of Pro212-Ile276 sequence of human protein C to its anticoagulant
      and profibrinolytic activity.
AB  - Activated protein C exhibits strong anticoagulant and profibrinolytic properties.
      The Pro212-Ile276 fragment of a heavy chain of the protein molecule is located in
      the nearest neighborhood of the catalytic domain. It was found that polyclonal
      antibodies against this fragment recognize the sequence in the native molecule.
      To determine the contribution of the fragment in the anticoagulant and
      profibrinolytic activities of the enzyme, competitive inhibition analyses were
      performed. We found that amidolytic activity of the enzyme was inhibited by the
      recombinant Pro212-Ile276 fragment in a dose-dependent manner. Also, the fusion
      protein prolonged the time of clot lysis in a micro-clot lysis assay. The
      presence of the recombinant protein fragment did not influence the reaction of
      activated protein C with factor Va, neither the reaction of the enzyme with its
      specific inhibitor. We conclude, that Pro212-Ile276 region of protein C can not
      be identified with the binding pocket of the enzyme, but might be a binding site
      for small, low molecular weight substrates like chromogenic substrate.

PMID- 9630310
TI  - Evaluation of clotting and fibrinolytic activation after protracted physical
      exercise.
AB  - The behavior of hemostatic system activation during protracted physical exercise
      is well known, but the duration of its modification is not yet defined. In order
      to evaluate the time of hemostatic system activation after prolonged strenuous
      endurance physical exercise (typical marathon race: 42.195 km, v=15.35 km/h; mean
      length of time run 2.45+/-0.15 hours) 12 well-trained long-distance male runners
      (mean age: 35+/-7, range 25-47 years) were investigated. Blood samples were drawn
      in the morning on the day before the performance, immediately after the race, and
      24 hours and 48 hours after the end of run. With respect of baseline, immediately
      after the race, a significant decrease of fibrinogen (-25%) and significant
      increases of prothrombin fragment 1+2 (+633%) and thrombin-antithrombin complex
      (+848%) were observed. A significant acceleration of euglobulin lysis time (
      41%), and rises of plasma levels of tissue plasminogen activator antigen (+361%),
      plasminogen activator inhibitor type 1 antigen (+235%), d-dimer (+215%), and
      plasma fibrinogen degradation products (+1200%) were also found. Only a slight,
      yet not significant, decrease in plasminogen activator inhibitor type 1 activity
      was observed. One day after the end of marathon different parameters were still
      unchanged. Forty-eight hours after the competition all parameters investigated
      returned to baseline values. These results indicate a persistence of clotting as
      well as fibrinolysis activation up to 24 hours after the end of the race.

PMID- 9630311
TI  - In-vitro and ex-vivo neutralizing effect of protamine sulphate on the
      anticoagulant activity of a new low molecular mass heparin.

PMID- 9630312
TI  - Lack of association between platelet glycoprotein IIb/IIIa receptor PlA
      polymorphism and coronary artery disease or carotid intima-media thickness.

PMID- 9630313
TI  - Possibility of checking compliance and efficacy of antiaggregatory treatment
      following femoro-popliteal vein bypass surgery.

PMID- 9630314
TI  - Bone marrow transplants using unrelated donors.
AB  - HLA matching is still most important factor in bone marrow transplantation in
      unrelated donors, however, with the use of different and modern HLA/DNA typing
      techniques, it is becoming clear that many transplants have been performed with a
      significant degree of HLA mismatching, in particular, for HLA class I. The impact
      of this is in the context of donor selection, HLA matching and potential
      implications in the outcome of bone marrow transplantation is discussed in this
      paper.

PMID- 9630315
TI  - Hematopoietic stem cells from different sources: biological and technical
      aspects.
AB  - Hematopoietic stem cell (HSC) enumeration is crucial to predict the engraftment
      potential of a given HSC collection, and currently involves the surrogate count
      of nucleated cells, CFU or CD34+ cells. However, there is raising evidence that
      CFU are HSC involved in short-term but not in long-term reconstitution, and that
      only a small fraction of all CD34+ cells have long term multilineage engraftment
      potential. In this regard, there is evidence that cord blood (CB), bone marrow
      (BM) and peripheral blood (PB) derived HSC are highly heterogeneous for a number
      of antigens useful for HSC enumeration by flow cytometry. Moreover, there is a
      raising evidence that a CD34 human HSC might exist. The CD34 HSC has been already
      described in animals and in human Hoechst 33342 negative HSC. This
      notwithstanding, clinical data have clearly demonstrated that purified allogeneic
      CD34+ cells can reconstitute the myeloid and the lymphoid lineages in
      myeloablated recipients. In the lack of a suitable marker for CD34 HSC
      enumeration, it is hard to predict the role of CD34 HSC in hematopoietic
      reconstitution after transplantation. On the other hand, these cells might be a
      better target for HSC expansion and gene transfer.

PMID- 9630316
TI  - Peripheral blood progenitor cells for autologous transplant in children.
AB  - Autologous peripheral blood progenitor cell transplantation has become an
      accepted procedure to support high dose chemotherapy in adults and children with
      cancer. The use of hematopoietic growth factors alone for mobilization of PBSC
      avoids the potential side effects of myelotoxic regimens and is as effective in
      reconstituting hematopoiesis as other mobilization methods. Many problems
      associated with apheresis procedures arise when PBPCs are harvested in small
      children. Large-volume-leukapheresis using a continuous flow blood cell separator
      allows us the collection of peripheral blood stem cells in children, even in the
      small ones. The speed of hematological recovery highly correlates with the number
      of CD34+ infused cells. We consider that a CD34+ cell dose of 5.0 x 10(6)/kg may
      be sufficient to ensure a rapid neutrophil and platelet recovery in pediatric
      patients mobilized by G-CSF.

PMID- 9630317
TI  - Haematopoietic progenitor cell transplant in acute leukaemias in children:
      indications, results and controversies.
AB  - The objective of this study was to update the role of different modalities of
      haematopoietic progenitor cell transplants (PCT) in the therapy of acute
      leukaemias in children emphasizing the points of agreement and controversy. In
      AML in first remission, allogeneic PCT from an HLA-identical sibling is the
      treatment of choice in most cases, DFS of 60-80% has been attained in paediatric
      series. Indications appear clear except in M3 subtype, M7 in children with Down
      syndrome and possibly in patients with M2 and t(8;21) and MS-Eo and inv(16) who
      have a good early response to induction treatment. In some paediatric series,
      results with autologous transplants (APCT) are similar to those obtained with
      allo-PCT and superior to those obtained with chemotherapy alone, but this point
      is controversial. Allo-PCT and APCT are indicated in children in second
      remission, yielding 40% DFS. In children with ALL in first remission, indications
      for PCT are limited to only 8-10% of patients with very-high risk of relapse,
      mainly those with certain chromosome abnormalities or with poor or late response
      to induction treatment; a favourable outcome has been registered in 60%. Allo-PCT
      is the best choice for patients in second remission after an early marrow relapse
      and who have an adequate related or unrelated donor; DFS of 40-50% has been
      described in several paediatric series. Indications of allo-PCT from related
      donors after late bone marrow relapses or early extramedullary relapses appears
      more controversial but there are data in its favour. The role of APCT appears
      even more controversial but some authors favour its use in these situations. In
      more advanced stages of the disease the results obtained with allo-PCT are poorer
      (DFS between 10 and 20%). In summary, although many controversial points with
      regards to indications and modalities of transplants in acute leukaemia in
      children remain, it must be emphasized that with advances in both fields,
      chemotherapy and transplants, today 80% of children with ALL and 60-70% of those
      with AML are cured and enjoy good-quality of life.

PMID- 9630318
TI  - Allogeneic transplantation of haematopoietic progenitors for myelodysplastic
      syndromes and myeloproliferative disorders.
AB  - Since children with myelodysplastic syndromes (MDS) and myeloproliferative
      disorders (MPD) have a poor prognosis and conventional chemotherapy did not prove
      to be effective in eradicating them, paediatric patients affected by these
      diseases and with an HLA-histocompatible donor are to be considered elective
      candidates for allogeneic transplantation of haematopoietic stem cells (HSC). For
      those patients with a compatible sibling relapse remains the most important
      problem, whereas in children transplanted from alternative donors graft rejection
      and transplant-related mortality significantly contribute to treatment failure. A
      detailed analysis on the different patient, disease and treatment factors
      correlated with transplant outcome in childhood MDS and MPD is discussed.

PMID- 9630319
TI  - Bone marrow transplantation in congenital immunodeficiency diseases.
AB  - Bone Marrow transplantation (BMT) is the treatment of choice in a large number of
      primary immunodeficiencies, for which this treatment is potentially curative. BMT
      needs to be considered as soon as possible after diagnosis because these
      disorders usually run an unpredictable course and may be rapidly fatal. Beside
      conventional HLA-matched donor BMT, there is growing and increasingly favourable
      experience with alternative, in particular HLA-haploidentical donors. In this
      review, current results of BMT are presented.

PMID- 9630320
TI  - Allogeneic stem cell transplantation for Fanconi Anaemia. Severe Aplastic Anaemia
      Working Party of the EBMT and EUFAR. European Group for Blood and Marrow
      Transplantation.
AB  - Fanconi anaemia is a hereditary disorder characterised by chromosomal breaks
      increased by cross-linking agents. Bone marrow transplantation is the treatment
      of choice when a HLA identical sibling donor has been identified. The use of low
      dose cyclophosphamide with thoraco-abdominal irradiation for the conditioning
      regimen of FA patients has lead to a dramatic improvement of survival, with a
      long-term survival of 75% at our institution. However, if most patients are
      completely cured of their haematological disease, there is concern about an
      increased frequency of secondary tumours, mostly head and neck squamous cell
      carcinomas of poor prognosis. Results of BMT using alternative donors (HLA
      mismatched related and unrelated donors) have also improved during the last
      decade. A better selection of the donor via high-resolution techniques for class
      II HLA matching, and more recently the use of T cell depleted grafts are probably
      the main explanations. Despite a short follow-up and the small number of patients
      analysed, transplants using HLA matched family cord blood give some promising
      results. On the other hand, first results with unrelated cord blood remind that
      this approach is clearly an experimental one that has to be evaluated through
      international registries and prospective studies. New approaches including
      autologous stem cell transplantations and gene therapy are currently explored.

PMID- 9630321
TI  - Indications and results of progenitor cell transplant in congenital haemopathies
      (except Fanconi anaemia).

PMID- 9630322
TI  - Bone marrow transplantation and gene therapy for lysosomal storage diseases.
AB  - Allogeneic bone marrow transplantation with marrow from HLA-identical donors has
      been used with increasing frequency to treat patients with lysosomal storage
      diseases. The effects of bone marrow transplantation largely depend on the type
      and stage of the disease. Generally, 'visceral symptoms' can be largely improved
      by transplantation, but skeletal lesions are relatively unaffected by
      transplantation. The effect on neurological symptoms varies.

PMID- 9630323
TI  - Unrelated donor marrow transplantation for inborn errors.
AB  - From December 1989 to December 1997 40 children aged 1 year to 19 years with
      inborn errors other than severe combined immunodeficiencies underwent unrelated
      donor (UD) bone marrow transplantation (BMT) in one of 10 institutions of the
      Italian Bone Marrow Transplant Group participating in this program. The diseases
      leading to BMT included Fanconi Anemia (10), Thalassemia (8), Wiskott Aldrich
      syndrome (5), haemophagocytic lymphohystiocytosis (6), osteopetrosis (3), storage
      diseases (6), Chediak Higashi syndrome (1), Schwachman syndrome (1). Thirty-three
      pairs were A, B, DRB1 matched. Three pairs were one antigen mismatched and one
      pair was two antigens mismatched. The remaining three pairs lacked information on
      molecular biology. Twelve children underwent a preparative regimen including
      radiotherapy. The remaining 28 children were conditioned with a chemotherapy
      regimen which included Busulfan. GvHD disease prophylaxis included CSA and MTX
      alone (9) or associated with ALG (17) or in vivo Campath 1G (12). The remaining
      two children received CSA alone. Thirty-five children showed donor engraftment;
      three children with thalassemia and one with osteopetrosis failed to engraft.
      Five children developed secondary graft failure. Actuarial 5 year disease-free
      survival was 62%; grade III-IV acute GvHD developed in seven of 38 evaluable
      children (18%); chronic GvHD developed in seven of 27 evaluable children (26%).
      We confirm that Wiskott Aldrich syndrome, HLH, and osteopetrosis represent an
      absolute indication for UD-BMT. Prognosis of UD-BMT for FA could improve in
      children grafted in an early phase, but a better preparative regimen has to be
      identified. UD-BMT in thalassemia is acceptable only in a restricted subset of
      patients selected for poor compliance to therapy.

PMID- 9630324
TI  - Haploidentical related transplants and unrelated donor transplants with T cell
      addback.
AB  - Only 30% of children have a matched family donor (MFD). Alternative donors can be
      found from volunteer unrelated donor (UD) panels, and almost every child has a
      haploidentical parental donor (Haplo). The outcome of alternative donor BMT has
      previously been inferior due to increased graft rejection and GVHD. The recent
      outcome of 121 consecutive children undergoing MFD, UD, and Haplo BMT between
      1994 and 1997 was analysed. [table in text] Preparative regimens for MFD/UD/Haplo
      BMT respectively included TBI in 30%/36%/11%, chemotherapy only in 59%/64%/89%,
      Campath 1G or none n 14%/ 0%/0%. The balance of GVHD and rejection was addressed
      by T-cell depletion (Campath 1M) in 2/71 MFD BMTs, T-cell depletion with addback
      of 5 x 10(4) T cells/kg on day zero in 33/41 UD BMTs, and T cell depletion of
      purified mobilised peripheral blood CD34+ cells and bone marrow in 9/9 Haplo
      BMTs. Stable engraftment was achieved in 68/71, and 35/41 (one patient after 2nd
      BMT) and 7/9 MFD, UD, and Haplo BMTs respectively. Median follow up, survival,
      disease free survival and, death rates for MFD/UD/Haplo BMT were 12/12/12 months,
      74%/77%/78%, 69%/67%/67%, and 27%/23%/23% respectively. Within a wide range of
      paediatric diseases the outcome of alternative donor BMT now parallels that of
      MFD BMT.

PMID- 9630325
TI  - GVHD: overview on pathophysiology, incidence, clinical and biological features.
AB  - Acute and chronic graft-versus-host disease (GVHD) develop in a significant
      proportion of transplant recipients and still represent one of the major causes
      of morbidity and mortality after allogeneic BMT. Prevention of GVHD does not only
      attempt to reduce acute toxicity and morbidity of transplantation but also to
      ameliorate long term outcome. GVHD is a T-cell mediated disease affecting
      multiple target organ systems. Recent research has tremendously improved our
      understanding of the pathophysiology of the disease. These new data are reviewed
      with main emphasis on their impact for children. The most important task for the
      future will be to make these new strategies fruitful for clinical application.

PMID- 9630326
TI  - Cyclosporine-A as GVHD prophylaxis in allogeneic BMT for childhood acute
      leukemia. AIEOP-BMT group.
AB  - We report the preliminary results of a prospective randomized study on the impact
      of two different dosages of Cyclosporine A (Cs-A) on probability of development
      of acute and chronic GVHD, transplant-related mortality (TRM), relapse rate (RR)
      and event-free survival (EFS). Fifty-nine pediatric patients given BMT from an
      HLA-identical sibling were centrally randomized to receive either Cs-A at a
      dosage of 1 mg/kg/die (CsA1) or at a dosage of 3 mg/kg/die (CsA3) intravenously
      for the first 21 days after BMT. Patients given Cs-A at a dosage of 1 mg/kg/die
      had a higher probability of developing acute GVHD, but a lower relapse rate,
      which translated into a better probability of EFS. These preliminary results to
      be confirmed with a longer follow-up suggest that the use of low doses of CsA is
      feasible even though associated with a higher incidence of GVHD, but without any
      increment in TRM. The reduction of immunosuppressive treatment after BMT favoured
      the development of a graft-versus-leukemia effect, which seems to play a relevant
      role in preventing leukemia recurrence and in improving the cure rate.

PMID- 9630327
TI  - CMV-viraemia during allogenic bone marrow transplantation in paediatric patients:
      association with survival and graft-versus-host disease.
AB  - Sixty-one consecutive paediatric patients undergoing allogenic bone marrow
      transplantation (BMT) were screened prospectively for cytomegalovirus (CMV)
      viraemia by PCR. Sixteen patients (26%) presented with single or recurrent CMV
      viraemia between day -7 and + 100. Although only four of them had evidence of CMV
      disease, there was a significant difference in the incidence of acute Graft
      versus Host Disease (GVHD) grade III-IV (75% vs 15.5%), liver-involvement (68% vs
      13%) and the incidence of chronic GVHD (83% vs 13.8%) between CMV-PCR-positive
      and CMV-PCR-negative patients. Transplant-related mortality (TRM) was 43.7% in
      the CMV-PCR-positive group versus 13% in patients which had no evidence for CMV
      viraemia. In all but one cases mortality in CMV-PCR positive patients was GVHD
      associated. Pre-emptive therapy with gancyclovir in case of CMV-viraemia seemed
      to have no impact on incidence and severity of GVHD.

PMID- 9630328
TI  - Proposal for standard recommendations for prophylaxis of graft-versus-host
      disease in children. European Group for Blood and Marrow Transplantation (EBMT)
      Working Party Paediatric Diseases and the International Study Committee of the
      BFM family-subcommittee Bone Marrow Transplantation (IBFM-STG).
AB  - Great variations exist in the practices of graft-versus-host disease prophylaxis
      for children undergoing allogeneic stem cell transplantation. It was the aim of
      the EBMT Working Party on Paediatric Diseases and the International Study Group
      of the BFM-Family, subcommittee bone marrow transplantation (IBFM-SG) to define
      standard recommendation for prevention of GVHD. Thus a survey was carried out
      among the local representatives of the EBMT WP and IBFM-SG members to define
      standards for GVHD prophylaxis basing on available literature data, discussion
      with colleagues and their own experience. Presently the majority of regimen for
      GVHD prophylaxis are centred on CsA and a short course of MTX with addition of
      some other immunosuppression (eg ATG or ALG) in patients with high risk for
      severe GVHD. The proposal defined different category of patients: patients with
      malignant disease who are either transplanted from HLA matched sibling donors or
      HLA mismatched family donors (or volunteer unrelated donors) and patients with
      non malignant disease who might not benefit from graft-versus-leukaemia effect
      having either an HLA matched sibling donor or an HLA mismatched family donor (or
      volunteer unrelated donor). Homogeneous GVHD prophylaxis for defined patient
      groups should provide better information to optimise strategies in reducing
      treatment related toxicity and incidence of relapse by increasing GVL effect.

PMID- 9630329
TI  - Long-term survivors: an overview on late effects, sequelae and second neoplasias.
AB  - A large number of haematological and oncological diseases as well as inborn
      errors can be cured today by stem cell transplantation. However, the chemotherapy
      and radiation used for the preparation of BMT can induce late effects which can
      be rather severe. Especially in malignant diseases the late toxicity of previous
      conventional therapy has an additional impact. The function of various organs can
      be impaired, such as the eyes, the central nervous system, the teeth, the legs,
      the heart, the kidneys, the liver, the endocrine functions and growth. Second
      neoplasias occur during various times after BMT: lymphoproliferative disease may
      occur during the first year, leukemias and myelodysplastic syndromes develop
      after several years, whereas solid tumours occur even later. The incidence of
      second neoplasias after BMT seems to be higher in children than in adults. Many
      late sequelae as well as psychological disturbances can impair the quality of
      life of the survivors of BMT. Paediatricians should take this fact into account
      when they think about stem cell transplantation in a child. This all means that a
      long-term observation in these persons is necessary and this is done best within
      a standardised follow-up programme. Meanwhile such programmes have been developed
      in some countries, and this should be promoted within the working party
      'Paediatric Diseases' of EBMT.

PMID- 9630330
TI  - Endocrine late effects in children who underwent bone marrow transplantation:
      review.
AB  - With the increasing use and success of BMT, larger numbers of children survive
      transplantation. Still, cancer treatment in children causes damage to the
      endocrine glands, often inducing growth deficiency, pubertal delay and thyroid
      dysfunction. This paper will deal with some of the most common endocrine
      disorders related to BMT in the pediatric population. Irradiation is the major
      contributor for growth impairment after BMT, acting through lesion to epiphyseal
      growth-plate, gonadal damage with delayed or precocious puberty, hypothyroidism,
      and growth hormone insufficiency. Gonadal dysfunction can be induced both by a
      direct injury to the gonads (irradiation, gonadotoxic agents) causing primary
      hypergonadotropic-hypogonadism, and with less frequency, by neuroendocrine injury
      to the hypothalamo-pituitary axis causing hypogonadotropic-hypogonadism. It seems
      that both doses of chemotherapy and of irradiation used by different regimens,
      fractionation of irradiation, and age at the time of BMT are the most important
      factors when we deal with toxic endocrine late-effects in long term survivors. In
      order to improve the quality of life of each single patient who receive BMT, and
      without inflicting the success-rate of this procedure, we recommend a life-long
      surveillance to prevent or to treat symptoms and disorders caused by hormone
      deficiencies, and we also advocate for a multidisciplinary team-approach that
      includes an endocrinologist consultant.

PMID- 9630331
TI  - Quality of life in young adults having received a BMT during childhood: a GETMON
      study. Grupo Espanol de Trasplante de Medula Osea en el Nino.
AB  - A quality-of-life questionnaire study was administered in a group of 98 disease
      free survivors more than 3 years after BMT. All participants were over the age of
      17 years at the time of the survey. The transplants were performed between 1981
      and 1993 in eight Spanish hospitals. Eighty-three percent of patients had
      undergone BMT for neoplastic disease. Seventy-three per cent received an
      allogeneic bone marrow transplantation. A modified version of a questionnaire
      applied in Stanford Hospital to evaluate quality of life in adults after BMT was
      used. A single investigator was responsible for interviewing all subjects by
      telephone. We compare these results with the same questionnaire applied in a
      control group of 58 healthy subjects of similar age. The most significant results
      were: BMT patients valued their quality of life more highly than the control
      group. The mean score for global quality of life was 8.19+/-0.17 in BMT group as
      compared to 7.54+/-0.13 in control group (P=0.0013). Studies were cited as the
      major concern in both groups: 24% in BMT group and in 69% in control group (C.I.
      95%=0.59 to 0.30). The patients in the BMT group considered they had fewer
      problems in comparison with the control group regarding interpersonal
      relationships with family members and friends, sleep, depression and leisure
      possibilities. However, they considered they had more problems concerning their
      physical appearance, studies and work possibilities than their peers.
      Considerations regarding weight, height, sexual functioning, anxiety, tendency to
      suffer illness and problems with insurance were similar in both groups.

PMID- 9630332
TI  - Immune reconstitution and viral infections after stem cell transplantation.
AB  - Viral infections are important in SCT patients. Different viruses are challenges
      for the physician at different times after transplantation due to changing
      defects in the immune status of the patients. Infections with respiratory viruses
      in particular respiratory syncytial virus are important early after transplant
      but the knowledge about epidemiology, risk factors, and treatment is still
      limited. Parainfluenza and influenza viruses can also cause severe and sometimes
      fatal infections after SCT. During the acute GVHD phase, CMV has been the most
      important viral infection during the entire history of allogeneic SCT. Recent
      developments with antiviral prophylaxis, new techniques for early diagnosis, and
      the strategy of preemptive antiviral therapy has reduced its importance in
      matched sibling transplants. Instead CMV disease occurring late after SCT has
      become an increasingly important problem in patients who have undergone unrelated
      or mis-matched SCT due to poor development of T-cell function. Other
      herpesviruses such as human herpesvirus type 6 and EBV are also becoming
      important causes of severe complications after unrelated and mismatched SCT. For
      this group of patients new innovative preventive and therapeutic strategies are
      needed.

PMID- 9630333
TI  - Infections with hepatotropic viruses in children treated with allogeneic bone
      marrow transplantation.
AB  - Patients treated with BMT are extremely susceptible to infection with blood-borne
      viruses that can cause liver disease of variable clinical severity, from minimal
      biochemical changes to fulminant hepatic failure. Facing a patient with liver
      disfunction after BMT, one must bear in mind that more than one cause of liver
      disease, of viral and/or non-viral origin, may coexist. Moreover, besides the
      most important hepatotropic viruses, other agents, like herpesviruses (including
      CMV, adenoviruses, Epstein-Barr virus) may also be implicated, sometimes causing
      a life-threatening fulminant hepatitis, due to their cytopatic effect. Liver
      disease history and viral markers before transplant, together with the accurate
      assessment of the timing and type of clinical and biochemical deterioration are
      useful tools for a differential diagnosis. Liver biopsy, if taken in the early
      posttransplant period, is often difficult to interpret, while in case of liver
      disease occurring during immunosuppression tapering, histologic examination may
      discriminate between an exacerbation of viral hepatitis and an acute onset of
      chronic liver GVHD. While it seems that hepatitis G virus does not cause liver
      disease, the presence of hepatitis B virus (HBV) or hepatitis C virus (HCV)
      infection is a matter of concern for its consequences both early after BMT and
      for long-term survivors. Despite screening for blood and marrow donors for HBV
      and, more recently, for HCV markers, the rate of post-transplant infection (4%
      and 4-15% respectively, confirmed in prospective studies) with those viruses
      indicates that viral hepatitis still remains an important clinical problem in
      this setting, although the prognosis of chronic HCV and HBV infection appears
      more benign than expected, especially in children.

PMID- 9630334
TI  - Bacterial and fungal infections in children undergoing bone marrow
      transplantation.
AB  - Bacterial and fungal infections in pediatric BMT recipients are major causes of
      morbidity and mortality, although less than those in the adult BMT population.
      Early in the post-BMT period, when patients are neutropenic, the predominant
      pathogens are Gram-negative bacteria, mainly E. coli, K. pneumoniae and P.
      aeruginosa; Gram-positive bacteria, mainly coagulase-negative staphylococcus, S.
      viridans and E. faecalis; and fungi, mainly Candida spp. and Aspergillus spp. The
      emerging resistance of a variety of pathogens is of major concern and limits the
      use of prophylactic antibiotics. Mortality from invasive fungal infections is
      much greater than that caused by bacterial pathogens. Many centers are currently
      using prophylactic fluconazole, which may lead to emergence of infections with C.
      krusei and T. glabrata. Patients with GvHD are at continuous risk from bacterial
      and fungal pathogens. Late in the post-BMT period, S. pneumoniae may cause
      septicemia, meningitis, pneumonia and other respiratory infections. This may
      occur months or years following transplantation, with a significant mortality
      rate in patients with chronic GvHD. Development of rapid and reliable diagnostic
      methods for identifying fungal pathogens and of new therapeutic approaches for
      treating invasive fungal infections are now our greatest future challenges.

PMID- 9630335
TI  - Competitive and selective antagonism of P2Y1 receptors by N6-methyl 2'
      deoxyadenosine 3',5'-bisphosphate.
AB  - The antagonist activity of N6-methyl 2'-deoxyadenosine 3',5'-bisphosphate
      (N6MABP) has been examined at the phospholipase C-coupled P2Y1 receptor of turkey
      erythrocyte membranes. N6MABP antagonized 2MeSATP-stimulated inositol phosphate
      hydrolysis with a potency approximately 20 fold greater than the previously
      studied parent molecule, adenosine 3',5'-bisphosphate. The P2Y1 receptor
      antagonism observed with N6MABP was competitive as revealed by Schild analysis
      (pK(B) = 6.99 +/- 0.13). Whereas N6MABP was an antagonist at the human P2Y1
      receptor, no antagonist effect of N6MABP was observed at the human P2Y2, human
      P2Y4 or rat P2Y6 receptors.

PMID- 9630336
TI  - Evidence that ATP acts at two sites to evoke contraction in the rat isolated tail
      artery.
AB  - 1. The site(s) at which P2-receptor agonists act to evoke contractions of the rat
      isolated tail artery was studied by use of P2-receptor antagonists and the
      extracellular ATPase inhibitor 6-N,N-diethyl-D-beta,gamma-dibromomethyleneATP
      (ARL 67156). 2. Suramin (1 microM(-1) mM) and pyridoxalphosphate-6-azophenyl
      2',4'-disulphonic acid (PPADS) (0.3-300 microM) inhibited contractions evoked by
      equi-effective concentrations of alpha,beta-methyleneATP (alpha,beta-meATP) (5
      microM), 2-methylthioATP (2-meSATP) (100 microM) and adenosine 5'-triphosphate
      (ATP) (1 mM) in a concentration-dependent manner. Responses to alpha,beta-meATP
      and 2-meSATP were abolished, but approximately one third of the peak response to
      ATP was resistant to suramin and PPADS. 3. Contractions evoked by uridine 5'
      triphosphate (UTP) (1 mM) were slightly inhibited by suramin (100 and 300 microM)
      and potentiated by PPADS (300 microM). 4. Desensitization of the P2X1-receptor by
      alpha,beta-meATP abolished contractions evoked by 2-meSATP (100 microM) and
      reduced those to ATP (1 mM) and UTP (1 mM) to 15+/-3% and 68+/-4% of control. 5.
      Responses to alpha,beta-meATP (5 microM) and 2-meSATP (100 microM) were abolished
      when tissues were bathed in nominally calcium-free solution, while the peak
      contractions to ATP (1 mM) and UTP (1 mM) were reduced to 24+/-6% and 61+/-13%,
      respectively, of their control response. 6. ARL 67156 (3-100 microM) potentiated
      contractions elicited by UTP (1 mM), but inhibited responses to alpha,beta-meATP
      (5 microM), 2-meSATP (100 microM) and ATP (1 mM) in a concentration-dependent
      manner. 7. These results suggest that two populations of P2-receptors are present
      in the rat tail artery; ligand-gated P2X1-receptors and G-protein-coupled P2Y
      receptors.

PMID- 9630337
TI  - The effect of a transmembrane amino acid on etomidate sensitivity of an
      invertebrate GABA receptor.
AB  - 1. The gamma-aminobutyric acid (GABA)-modulatory and GABA-mimetic actions of
      etomidate at mammalian GABA(A) receptors are favoured by beta2- or beta3- versus
      beta1-subunit containing receptors, a selectivity which resides with a single
      transmembrane amino acid (beta2 N290, beta3 N289, beta1 S290). Here, we have
      utilized the Xenopus laevis oocyte expression system in conjunction with the two
      point voltage clamp technique to determine the influence of the equivalent amino
      acid (M314) on the actions of this anaesthetic at an etomidate-insensitive
      invertebrate GABA receptor (Rdl) of Drosophila melanogaster. 2. Complementary RNA
      injected oocytes expressing the wild type Rdl GABA receptor and voltage-clamped
      at -60 mV responded to bath applied GABA with a concentration-dependent inward
      current response and a calculated EC50 for GABA of 20+/-0.4 microM. Receptors in
      which the transmembrane methionine residue (M314) had been exchanged for an
      asparagine (RdlM314N) or a serine (RdlM314S) also exhibited a concentration
      dependent inward current response to GABA, but in both cases with a reduced EC50
      of 4.8+/-0.2 microM. 3. Utilizing the appropriate GABA EC10, etomidate (300
      microM) had little effect on the agonist-evoked current of the wild type Rdl
      receptor. By contrast, at RdlM314N receptors, etomidate produced a clear
      concentration-dependent enhancement of GABA-evoked currents with a calculated
      EC50 of 64+/-3 microM and an Emax of 68+/-2% (of the maximum response to GABA).
      4. The actions of etomidate at RdlM314N receptors exhibited an enantioselectivity
      common to that found for mammalian receptors, with 100 microM R-(+)-etomidate and
      S-(-)-etomidate enhancing the current induced by GABA (EC10) to 52+/-6% and 12+/
      1% of the GABA maximum respectively. 5. The effects of this mutation were
      selective for etomidate as the GABA-modulatory actions of 1 mM pentobarbitone at
      wild type Rdl (49+/-4% of the GABA maximum) and RdlM314N receptors (53+/-2% of
      the GABA maximum) were similar. Additionally, the modest potentiation of GABA
      produced by the anaesthetic neurosteroid 5alpha-pregnan-3alpha-ol-20-one (Rdl =
      25+/-4% of the GABA maximum) was not altered by this mutation (RdlM314N = 18+/-3%
      of the GABA maximum). 6. Etomidate acting at beta1 (S290)-containing mammalian
      GABA(A) receptors is known to produce only a modest GABA-modulatory effect.
      Similarly, etomidate acting at RdlM314S receptors produced an enhancement of GABA
      but the magnitude of the effect was reduced compared to RdlM314N receptors. 7.
      Etomidate acting at human alpha6beta3gamma2L receptors is known to produce a
      large enhancement of GABA-evoked currents and at higher concentrations this
      anaesthetic directly activates the GABA(A) receptor complex. Mutation of the
      human beta3 subunit asparagine to methionine (beta3 N289M found in the equivalent
      position in Rdl completely inhibited both the GABA-modulatory and GABA-mimetic
      action of etomidate (10-300 microM) acting at alpha6beta3 N289Mgamma2L receptors.
      8. It was concluded that, although invertebrate and mammalian proteins exhibit
      limited sequence homology, allosteric modification of their function by etomidate
      can be influenced in a complementary manner by a single amino acid substitution.
      The results are discussed in relation to whether this amino acid contributes to
      the anaesthetic binding site, or is essential for transduction. Furthermore, this
      study provides a clear example of the specificity of anaesthetic action.

PMID- 9630338
TI  - Endogenous orphanin FQ: evidence for a role in the modulation of
      electroacupuncture analgesia and the development of tolerance to analgesia
      produced by morphine and electroacupuncture.
AB  - 1. Our previous work has demonstrated that exogenously administered orphanin FQ
      (OFQ) antagonizes morphine analgesia and electroacupuncture analgesia (EAA) in
      the brain and potentiates morphine analgesia and EAA in the spinal cord of the
      rat. In the present study we evaluated the role of endogenously released OFQ in
      the development of tolerance to morphine and electroacupuncture (EA) and the
      analgesia produced by electroacupuncture, by use of the IgG fraction of an anti
      OFQ antibody (OFQ-Ab) microinjected into the rat central nervous system (CNS). 2.
      EAA was produced by stimulating rats at a frequency of 100 Hz. Rats were
      classified as either high responders (HR) or low responders (LR) based on the
      analgesic effects of EA. LRs could be converted into HRs by the
      intracerebroventricular (i.c.v.) microinjection of OFQ-Ab at both 1:1 and 1:10
      dilutions but not 1:100. HRs could be changed into LRs by the intrathecal (i.t.)
      injection of OFQ-Ab at both 1:1 and 1:10 dilutions, but not 1:100. 3. Acute
      morphine tolerance was induced in rats by repeated subcutaneous (s.c.) injections
      of morphine (5 mg kg, every 2 h) for 16 h. When injected i.c.v. the OFQ-Ab (1:1
      dilution) had no effect on the development of acute morphine tolerance. 4.
      Chronic morphine tolerance was produced in rats by repeated injection of morphine
      (5-60 mg kg, s.c., 3 x a day) for 6 days. I.c.v. injection of OFQ-Ab (1:1
      dilution) reversed this type of morphine tolerance in rats by 50% (P < 0.01). 5.
      Acute tolerance to the analgesia produced by EA developed after 6 h of continuous
      (100 Hz, 3 mA) stimulation. This tolerance was almost completely reversed by the
      i.c.v. injection of OFQ-Ab (1:1 dilution) (P < 0.05). 6. Chronic tolerance to the
      analgesic effect of EA was produced by repeatedly administering increasing
      current (1, 2 and 3 mA, each lasting for 10 min, for a total of 30 min) at a
      frequency of 100 Hz once a day for 6 days. I.c.v. injection of OFQ-Ab (1:1
      dilution) reversed this kind of tolerance by 50% (P < 0.01). 7. Together these
      results suggest that 100 Hz EA may enhance the release of endogenous OFQ in the
      CNS of the rat, which in turn may act to antagonize EA-produced analgesia in the
      brain but potentiate EA produced analgesia in the spinal cord. Therefore, OFQ
      appears to play an important role in the development of tolerance to the
      analgesic effects produced by EA. 8. The mechanisms underlying the development of
      acute morphine tolerance and chronic morphine tolerance appear to be different.
      Central OFQ may play an important role in the development of tolerance after
      chronic morphine administration.

PMID- 9630339
TI  - The role of tachykinin NK1 and NK2 receptors in atropine-resistant colonic
      propulsion in anaesthetized guinea-pigs.
AB  - 1. The role of endogenous tachykinins on guinea-pig colonic propulsion was
      investigated by using potent and selective tachykinin NK1 and NK2 receptor
      antagonists. Colonic propulsion and contractions were determined by means of a
      balloon-catheter device, inserted into the rectum of guanethidine (68 micromol
      kg(-1), s.c., 18 and 2 h before)-pretreated, urethane-anaesthetized guinea-pigs.
      Propulsion of the device (dynamic model) was determined by measuring the length
      of the catheter expelled during 60 min filling of the balloon (flow rate 5 microl
      min(-1)). 2. In control conditions the tachykinin NK1 receptor antagonist SR
      140333 (1 micromol kg(-1), i.v.) did not affect either colonic propulsion or the
      amplitude of contractions. The tachykinin NK2 receptor antagonists MEN 10627 and
      MEN 11420 (1 micromol kg(-1), i.v.) increased colonic propulsion at 10 min (+120%
      and 150%, respectively) but at 60 min the effect was significant only for MEN
      10627 (+84%). SR 48968 (1 micromol kg(-1), i.v.) did not significantly enhance
      the colonic propulsion. None of these tachykinin NK2 receptor antagonists
      modified the amplitude of colonic contractions. In contrast, both atropine (6
      micromol kg(-1), i.v., plus infusion of 1.8 micromol h(-1)) and hexamethonium (55
      micromol kg(-1), i.v., plus infusion of 17 micromol h(-1)) abolished propulsion
      (81% and 87% inhibition, respectively) and decreased the amplitude of
      contractions (68% inhibition for either treatment). 3. In atropine-treated
      animals (6 micromol kg(-1), i.v., plus infusion of 1.8 micromol h(-1)), apamin
      (30 nmol kg(-1), i.v.) restored colonic propulsion (+416%) and increased the
      amplitude of contractions (+367% as compared to atropine alone). Hexamethonium
      (55 micromol kg(-1), i.v., plus infusion of 17 micromol h(-1)) abolished the
      apamin-induced, atropine-resistant colonic propulsion (97% inhibition) and
      reduced the amplitude of the atropine-resistant contractions (52% inhibition). 4.
      The apamin-induced, atropine-resistant colonic propulsion was inhibited by SR
      140333 (-69% at 1 micromol kg(-1)), SR 48968 (-78% at 1 micromol kg(-1)), MEN
      11420 (-59% at 1 micromol kg(-1)) and MEN 10627 (-50% at 1 micromol kg(-1)),
      although the latter effect was not statistically significant. The combined
      administration of SR 140,333 and MEN 10,627 (1 micromol kg(-1) for each
      antagonist) almost completely abolished colonic propulsion (90% inhibition). The
      amplitude of colonic contractions was also reduced by SR 140333 (-42%), SR 48968
      (-29%), MEN 11420 (-45%) but not by MEN 10627 (-16%). The combined administration
      of SR 140333 and MEN 10,627 reduced the amplitude of contractions by 47%. SR
      140603 (1 micromol kg(-1), i.v.), the less potent enantiomer of SR 140333, was
      inactive. 5. In control animals, apamin (30 nmol kg(-1), i.v.) enhanced colonic
      propulsion (+84%) and increased the amplitude of contractions (+68%), as compared
      to the vehicle. Hexamethonium (55 micromol kg(-1), i.v. plus infusion of 17
      micromol h(-1)) inhibited propulsion (86% inhibition) and decreased the amplitude
      of contractions (49% inhibition). SR 140333, SR 48968, MEN 11420, MEN 10627, or
      the coadministration of SR 140333 and MEN 10627 had no effect. 6. In a separate
      series of experiments, the mean amplitude of colonic contractions was also
      recorded under isovolumetric conditions through the balloon-catheter device kept
      in place at 75 mm from the anal sphincter (static model). In control conditions,
      neither SR 140333 nor MEN 11420 modified the amplitude of contractions. In
      atropine-pretreated guinea-pigs, SR 140333 and MEN 11420 (0.1-1 micromol kg(-1))
      dose-dependently decreased the amplitude of contractions. In apamin- and atropine
      pretreated animals, only the highest (1 micromol kg(-1)) dose of SR 140333 or MEN
      11420 significantly decreased the amplitude of contractions. The inhibitory
      potency of atropine (0.3-1 micromol kg(-1)) was similar in apamin-pretreated
      animals and in controls. 7. It was concluded that, in anaesthetized guinea-pigs,
      endogenous tachykinins, acting through both NK(1) and NK(2) receptors, act as non
      cholinergic excitatory neurotransmitters in promoting an apamin-evoked reflex
      propulsive activity of the distal colon.

PMID- 9630340
TI  - Further insights into the anti-aggregating activity of NMDA in human platelets.
AB  - 1. In the present study the effect of N-methyl-D-aspartate (NMDA) on thromboxane
      B2 synthesis and on [Ca2+]i was studied in human platelets. 2. NMDA (10(-7) M)
      completely inhibited the synthesis of thromboxane B2 from exogenous arachidonic
      acid (AA), while it did not interfere with the aggregating effect of the
      thromboxane A2 receptor agonist U-46619. 3. NMDA (0.1 microM - 10 microM) dose
      dependently increased intracellular calcium in washed platelets preloaded with
      fura 2 AM, and this effect was not additive with that of AA. 4. NMDA shifted the
      dose-response curve of AA to the right. At the highest AA concentrations platelet
      aggregation was not inhibited. 5. The antiaggregating effect of NMDA was not
      antagonized by N(G)-monomethyl-L-arginine (L-NMMA), a nitric oxide synthase (NOS)
      inhibitor. 6. Finally, NMDA (0.01 nM - 100 nM) associated with either aspirin or
      indomethacin significantly potentiated the antiaggregating activity of both cyclo
      oxygenase inhibitors. 7. It was concluded that NMDA is a potent inhibitor of
      platelet aggregation and thromboxane B2 synthesis in human platelet rich plasma
      (PRP).

PMID- 9630341
TI  - The receptor subtype mediating the action of angiotensin II on intracellular
      sodium in rat proximal tubules.
AB  - 1. An investigation was undertaken to explore the subtype of receptor involved in
      mediating the actions of angiotensin II on intracellular sodium content in
      suspensions of isolated proximal tubules of the rat. 2. Intracellular sodium
      content of the proximal tubules was measured with 23Na n.m.r. spectroscopy and
      under these conditions basal sodium content of the tubular cells was 69.04+/-1.73
      nmol mg(-1) dry weight and the ATP levels, at 8.3+/-0.9 nmol ATP mg(-1) protein,
      were consistent with active respiration by the tissue. 3. In the presence of 10(
      4) M PD123319, a selective non-peptide AT2 receptor antagonist, intracellular
      sodium levels rose from steady state by 30% (P < 0.01; n = 7) within 10 min of
      exposure to angiotensin II 10(-11) M. Over the subsequent 30 min steady state
      levels were re-established. Administration of angiotensin II 10(-11) M, in the
      presence of the selective AT1 receptor antagonist, losartan at either 10(-6) M (n
      = 5) or 10(-4) M (n = 6), was without effect on intracellular sodium levels,
      which were significantly different (P < 0.001) from those observed when PD 123319
      was present. 4. Angiotensin II 10(-5) M, administered to the tubular suspension
      in the presence of 10(-4) M PD123319, decreased (P < 0.01, n = 6) intracellular
      sodium content by 16% in the first 5 min, but in the following 25 min returned to
      steady state levels. However, in the presence of losartan 10(-4) M, angiotensin
      II 10(-5) M had no effect on intracellular sodium content which was markedly
      different (P < 0.001) from that obtained in the presence of PD123319. 5. These
      findings show that at both the high and low concentrations of angiotensin II, its
      modulation of intracellular sodium levels within the proximal tubule cells is
      mediated via the activation of AT1 receptors. The intracellular mechanism
      underlying this effect remain to be investigated.

PMID- 9630342
TI  - Modulation of spasmogen-stimulated Ins(1,4,5)P3 generation and functional
      responses by selective inhibitors of types 3 and 4 phosphodiesterase in airways
      smooth muscle.
AB  - 1. The effects of isoenzyme-selective inhibitors of phosphodiesterases PDE3 and
      PDE4 on cyclic AMP concentration, two indices of phosphoinositide hydrolysis, and
      contractile responses to spasmogens have been investigated in bovine tracheal
      smooth muscle (BTSM). 2. Neither the PDE3-selective inhibitor ORG 9935, nor the
      PDE4-selective inhibitor rolipram increased cyclic AMP levels in BTSM. However,
      rolipram addition in the presence of PDE3 inhibition (ORG 9935; 1 microM)
      concentration-dependently (-log EC50 (M), 6.55+/-0.15; n = 3) increased cyclic
      AMP levels to about 70% of the maximal response to the beta-adrenoceptor agonist
      isoprenaline. 3. Rolipram per se inhibited histamine-stimulated [3H]-inositol
      (poly)phosphate ([3H]-InsP(X)) accumulation by > 80% (-log EC50 (M), 6.92+/-0.11;
      n = 3). Although ORG 9935 (1 microM) had little effect on histamine-stimulated
      [3H]-InsP(X) accumulation alone it greatly facilitated the inhibitory action of
      rolipram (-log EC50 (M), 8.82+/-0.39; n = 3). The effects of PDE3 and/or PDE4
      inhibition on [3H]-InsP(X) accumulation stimulated by muscarinic acetylcholine
      (mACh) receptor activation were less marked. However, combined PDE3/4 inhibition
      significantly decreased this response at a submaximal concentration of mACh
      receptor agonist (carbachol; 1 microM). 4. The greater-than-additive effect of
      combined PDE3/4 inhibition was also observed at the level of contractile
      responses to histamine and carbachol. In experiments designed to investigate the
      effects of PDE3 and/or 4 inhibitors on the carbachol-mediated phasic contraction,
      additions of rolipram (10 microM) or ORG 9935 (1 microM) were without effect,
      whereas added together the inhibitors caused a significant (P < 0.01) 40%
      reduction in the peak phasic contractile response. 5. The effect on contraction
      correlated with a substantial inhibitory effect of PDE3/4 inhibition on the
      initial increase in inositol 1,4,5-trisphosphate (InsP3) accumulation stimulated
      by spasmogen. Thus, in the presence of ORG 9935 (1 microM) rolipram concentration
      dependently inhibited carbachol-stimulated InsP3 accumulation by > or = 50% (-log
      EC50 (M), 6.77+/-0.21; n = 4). 6. Carbachol (100 microM) addition caused a rapid
      decrease (by 67% at 10 s) in BTSM cyclic AMP level in the presence of PDE3/4
      inhibition. However, omission of Ca2+ from the incubation medium prevented the
      carbachol-evoked decrease in cyclic AMP and this coincided with a greater
      inhibition (> or = 80%) of the carbachol-stimulated InsP3 response. 7. These data
      indicate that combined PDE3 and PDE4 inhibition has greater-than-additive effects
      on second messenger and functional responses to spasmogens in BTSM. Furthermore,
      the ability of PDE3/4 inhibition significantly to attenuate mACh receptor
      mediated contractile responses, may be, at least in part, attributed to an effect
      exerted at the level of InsP3 generation.

PMID- 9630343
TI  - Differential mechanism for the cell surface sorting and agonist-promoted
      internalization of the alpha1B-adrenoceptor.
AB  - 1. Alpha1B-adrenoceptors are localized at a steady state in the plasma membrane
      in untreated cells, and internalize to intracellular vesicles when exposed to
      agonist. Flow cytometry analysis with an anti-N-terminus-antibody (1B-N1-C,
      (Hirasawa et al., 1996)) facilitated the quantification of cell surface alpha1B
      adrenoceptor. Also, the cellular distribution of alpha1B-adrenoceptors was
      visually monitored by immunocytochemical confocal microscopy. 2. Utilizing this
      combined approach, we have examined the molecular mechanism for cellular
      trafficking of alpha1B-adrenoceptors, including the process of sorting of the
      synthesized receptor protein to the cell surface, and the agonist-induced
      internalization. The two processes were separately examined by using alpha1B
      adrenoceptor inducible DDT1MF-2 cells for the sorting process and CHO cells
      stably expressing alpha1B-adrenoceptors for the agonist-promoted internalization.
      3. We examined the effects of cytochalasin D and mycalolide B (actin
      depolymerization agents), demecolcine (a microtubule disrupting agent), brefeldin
      A (an inhibitor of vesicular transport and Golgi function), bafilomycin A1 (a
      specific inhibitor of the vacuolar proton pump) or hyperosmotic sucrose treatment
      (that may inhibit clathrin-mediated endocytosis) on these processes. 4. We found
      that the agonist-promoted internalization was blocked by cytochalasin D and
      mycalolide B, while the cell surface sorting process was specifically blocked by
      brefeldin A, indicating that the two processes involve different components of
      the cellular endocytic machinery. 5. The experimental approach as exemplified in
      this study would provide a valuable system to study further the molecular
      mechanism(s) of cellular trafficking of G protein-coupled receptors.

PMID- 9630344
TI  - Nitric oxide regulation of monkey myometrial contractility.
AB  - 1. We evaluated the effect of the nitric oxide (NO) donor CysNO (S-nitroso-L
      cysteine) and endogenous NO upon spontaneous contractility in non-pregnant
      cynomolgus monkeys. We also assessed the role of intracellular guanosine 3',5'
      cyclic monophosphate ([cyclic GMP]i) as a second messenger for NO in monkey
      uterine smooth muscle. 2. CysNO reduced spontaneous contractility by 84% (P <
      0.05) at maximal concentrations, and significantly elevated [cyclic GMP]i (P <
      0.05). However, increases in [cyclic GMP]i were not required for CysNO-induced
      relaxations; CysNO inhibited contractile activity despite the complete inhibition
      of guanylyl cyclase by methylene blue or LY83,583. 3. Analogues of cyclic GMP had
      no significant effect upon spontaneous contractile activity. L-arginine produced
      a 62% reduction in spontaneous activity (P < 0.05) while D-arginine had no
      effect. The competitive nitric oxide synthase (NOS) inhibitor N(omega)-nitro-L
      arginine (L-NOARG) not only blocked L-arginine-induced relaxations, but also
      significantly increased spontaneous contractile activity when added alone (P <
      0.05); the inactive D-enantiomer of NOARG had no such effect. 4. While both
      endogenous NO and the NO donor CysNO relax monkey myometrium, this effect is not
      causally related to CysNO-induced elevations in [cyclic GMP]i. The failure of
      cyclic GMP analogues to alter monkey uterine smooth muscle tension also argues
      against a role for [cyclic GMP]i in the regulation of uterine contractility. Not
      only do these findings argue for the existence of a functionally-relevant NOS in
      the monkey uterus, but increases in contractile activity seen in the presence of
      NOS inhibitors suggest a role for NO in the moment-to-moment regulation of
      contractile activity in this organ.

PMID- 9630345
TI  - Carbachol stimulation of gastric acid secretion and its effects on the parietal
      cell.
AB  - 1. The acid secretagogue effect of gastrin is mainly mediated by the release of
      enterochromaffin-like (ECL) cell histamine, but the mechanism of muscarinic
      stimulation of acid secretion remains unclear. The results of studying
      aminopyrine uptake in isolated parietal cells, and histamine release in isolated
      ECL cells suggest that muscarinic agents may act both directly on the parietal
      cell and indirectly via histamine release from ECL cells. 2. We examined parietal
      and ECL cell responses to the muscarinic agent carbamylcholine (carbachol) in
      conscious rats and in rat isolated vascularly perfused stomachs. 3. Intravenous
      carbachol stimulated acid secretion in conscious gastric fistula rats and
      increased H+K+ ATPase mRNA abundance, indicating activation of parietal cells. In
      these experiments there was no increase in portal venous histamine, or in oxyntic
      mucosal histidine decarboxylase (HDC) enzyme activity and HDC mRNA abundance. 4.
      In rat isolated stomachs stimulated with carbachol in the dose range 10 nM(-1) mM
      only the 1 microM concentration increased venous histamine significantly. 5. We
      concluded that the muscarinic agent carbachol stimulates acid secretion and H+K+
      ATPase mRNA in vivo by a direct effect on the parietal cell, that does not depend
      on the release of ECL cell histamine.

PMID- 9630346
TI  - Discovery of novel melanocortin4 receptor selective MSH analogues.
AB  - 1. We synthesized a novel series of cyclic melanocyte stimulating hormone (MSH)
      analogues and tested their binding properties on cells transiently expressing the
      human melanocortin1 (MC1), MC3, MC4 and MC5 receptors. 2. We discovered that
      compounds with 26 membered rings of [Cys4,D-Nal7,Cys11]alpha-MSH(4-11) displayed
      specific MC4 receptor selectivity. The preference order of the different MC
      receptor subtypes for the novel [Cys4D-Nal7Cys11]alpha-MSH(4-11) analogues are
      distinct from all other known MSH analogues, particularly as they bind the MC4
      receptor with high and the MC1 receptor with low relative affinities. 3. HS964
      and HS014 have 12 and 17 fold MC4/MC3 receptor selectivity, respectively, which
      is much higher than for the previously described cyclic lactam and
      [Cys4,Cys10]alpha-MSH analogues SHU9119 and HS9510. 4. HS964 is the first
      substance showing higher affinity for the MC5 receptor than the MC1 receptor. 5.
      HS014, which was the most potent and selective MC4 receptor ligand (Ki 3.2 nM,
      which is approximately 300 fold higher affinity than for alpha-MSH), was also
      demonstrated to antagonize alpha-MSH stimulation of cyclic AMP in MC4 receptor
      transfected cells. 6. We found that a compound with a 29 membered ring of
      [Cys3,Nle10,D-Nal7,Cys11]alpha-MSH(3-11) (HS010) had the highest affinity for the
      MC3 receptor. 7. This is the first study to describe ligands that are truly MC4
      selective and a ligand having a high affinity for the MC3 receptor. The novel
      compounds may be of use in clarifying the physiological roles of the MC3, MC4 and
      MC5 receptors.

PMID- 9630347
TI  - Comparative, general pharmacology of SDZ NKT 343, a novel, selective NK1 receptor
      antagonist.
AB  - 1. The in vitro and in vivo pharmacology of SDZ NKT 343 (2-nitrophenyl-carbamoyl
      (S)-prolyl-(S)-3-(2-naphthyl)alanyl-N-benzyl-N- methylamide), a novel tachykinin
      NK1 receptor antagonist was investigated. 2. SDZ NKT 343 inhibited [3H]-substance
      P binding to the human NK1 receptor in transfected Cos-7 cell membranes (IC50 =
      0.62+/-0.11 nM). In comparison, in the same assay Ki values for FK888, CP 99,994,
      SR 140,333 and RPR 100,893 were 2.13+/-0.04 nM, 0.96+/-0.20 nM, 0.15+/-0.06 nM
      and 1.77+/-0.41 nM, respectively. SDZ NKT 343 showed a markedly lower affinity at
      rat NK1 receptors in whole forebrain membranes (IC50 = 451+/-139 nM). 3. SDZ NKT
      343 caused an increase in EC50 as well as reduction in the number of binding
      sites (Bmax) determined for [3H]-substance P, suggesting a non-competitive
      interaction at the human NK1 receptor. SDZ NKT 343 also caused a reduction in the
      maximum elevation of [Ca2+]i evoked by substance P (SP) in human U373MG cells and
      depressed the maximum [Sar9]SP sulphone-induced contraction of the guinea-pig
      isolated ileum. The antagonism of SP effects on U373MG cells by SDZ NKT 343 was
      reversible. 4. SDZ NKT 343 showed weak affinity to human NK2 and NK3 receptors in
      transfected Cos-7 cells (Ki of 0.52+/-0.04 microM and 3.4+/-1.2 microM,
      respectively). SDZ NKT 343 was inactive in a broad array of binding assays
      including the bradykinin B2 receptor the histamine H1 receptor, opiate receptors
      and adrenoceptors. SDZ NKT 343 only weakly inhibited the voltage-activated Ca2+
      and Na+ currents in guinea-pig dorsal root ganglion neurones. The enantiomer of
      SDZ NKT 343, (R,R)-SDZ NKT 343 was about 1000 times less active at human NK1
      receptors expressed in Cos-7 cell membranes. 5. Contractions of the guinea-pig
      ileum by [Sar9]SP sulphone were inhibited by SDZ NKT 343 in a concentration
      dependent manner, with an IC50 = 1.60+/-0.94 nM, while the enantiomer (R,R)-SDZ
      NKT 343 was 100 times less active (IC50 = 162+/-26 nM). In comparison, in the
      same assay IC50 values for other NK1 receptor antagonists CP 99,994, SR 140,333,
      RPR 100,893 and FK 888 were 2.90+/-07 nM, 0.14+/-0.02 nM, 11.4+/-2.9 nM and 2.4+/
      0.83 nM, respectively. 6. In anaesthetized guinea-pigs i.v. administered SDZ NKT
      343 antagonized [Sar9]SP sulphone-evoked bronchoconstriction (70% reduction at
      0.4 mg kg(-1), i.v.). Basal airway resistance, mean arterial blood pressure and
      heart rate were not affected. 7. In conclusion, SDZ NKT 343 is a highly selective
      NK1 receptor antagonist with high potency at the human and guinea-pig receptors.
      SDZ NKT 343 may be used as a potential novel therapeutic agent in human diseases
      where NK1 receptor hyperfunction is involved.

PMID- 9630348
TI  - Effect of the selective 5-HT1A receptor antagonist WAY 100635 on the inhibition
      of e.p.s.ps produced by 5-HT in the CA1 region of rat hippocampal slices.
AB  - 1. The actions of N-(2-(-4(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)
      cyclohexane carboxamide (WAY 100635), a novel and selective 5-hydroxytryptamine1A
      (5-HT1A) antagonist, on excitatory postsynaptic potentials (e.p.s.ps) were
      investigated by use of intracellular recordings in pyramidal cells of the CA1
      region of rat hippocampal slices. 2. WAY 100635 (10 nM) did not affect any of the
      investigated parameters of cell excitability such as membrane potential, total
      input resistance (Rin), firing threshold, action potential amplitude, action
      potential frequency adaptation, and slow afterhyperpolarization (sAHP) which
      follows repetitive firing of action potentials. WAY 100635 did not have any
      effect on either the slope or the amplitude of e.p.s.ps evoked by stimulation of
      the CA1 stratum radiatum. 3. Bath application of either 5-hydroxytryptamine (5
      HT, 10-30 microM) or 5-carboxamidotryptamine (5-CT, 300 nM) hyperpolarized the
      membrane potential (deltaVm = -4.1 +/- 0.9 and -6.0 +/- 0.9 mV, respectively),
      and reduced Rin (-25 +/- 8% and -18 +/- 1%, respectively). 5-HT blocked the
      action potential frequency adaptation and significantly reduced the amplitude of
      the sAHP that follows repetitive firing of action potentials. 4. 5-HT
      significantly decreased the amplitude of evoked e.p.s.ps (-14 +/- 6%). This
      effect was greater in the presence of the GABA(A) receptor antagonist bicuculline
      (10 microM, -45 +/- 12%) and was mimicked by 5-CT (-49 +/- 5%). Both AMPA and
      NMDA components of e.p.s.ps were significantly reduced in amplitude by 5-HT (-38
      +/- 8%, n = 6, and -29 +/- 12%, n = 3, respectively; P < 0.05). 5. WAY 100635
      fully antagonized the hyperpolarization, the reduction of Rin, and the decrease
      in amplitude of e.p.s.ps elicited by 5-HT, while it did not affect the action of
      5-HT on the action potential frequency adaptation. In the presence of WAY 100635,
      5-HT elicited a depolarization which was blocked by 10-30 microM RS 23597-190, a
      selective 5-HT4 receptor antagonist. 6. Our data demonstrate that WAY 100635 is
      devoid of direct effects on CA1 pyramidal cell excitability and on evoked
      e.p.s.ps, while it fully antagonizes the effects of 5-HT on excitatory synaptic
      transmission and on hyperpolarization, without affecting the 5-HT4 receptor
      mediated response. Since WAY 100635 selectively antagonizes 5-HT1A receptor
      mediated actions of 5-HT, our data also demonstrate that the inhibitory action of
      5-HT on excitatory synaptic transmission in CA1 is mediated by 5-HT1A receptors.

PMID- 9630349
TI  - Neuropeptide Y-induced potentiation of noradrenergic vasoconstriction in the
      human saphenous vein: involvement of endothelium generated thromboxane.
AB  - 1. We investigated the potentiating effect of low concentrations of neuropeptide
      Y (NPY) on the vasoconstriction induced by transmural nerve stimulation (TNS) and
      noradrenaline (NA) in human saphenous veins. The effects of (i) endothelium
      removal; (ii) the addition of the NO pathway precursor L-arginine; (iii) the
      ET(A)/ET(B) endothelin receptor antagonist Ro 47-0203; (iv) the cyclo-oxygenase
      inhibitor, indomethacin; (v) the selective thromboxane A2 (TxA2) receptor
      antagonists Bay u3405 and ifetroban, and (vi) the TxA2 synthase inhibitor, UK
      38485, were studied in order to gain information about the mechanisms of NPY
      induced potentiation. 2. Contractile response curves for TNS (0.5-8 Hz) and for
      exogenously administered NA (0.1-3 microM) were obtained in superfused saphenous
      vein rings. The contractions induced by both TNS and NA at all tested frequencies
      and concentrations, respectively, were significantly potentiated by 50 nM NPY in
      endothelium intact veins. Conversely, in endothelium-denuded vessel rings the
      contractile-response curves to TNS and NA overlapped both in the absence and
      presence of NPY, thus suggesting that a release of vasoactive substances from
      endothelial cells could account for the noradrenergic NPY-induced potentiation.
      3. In vessels with intact endothelium, the potentiating action of NPY on TNS and
      NA was unaffected by the presence of high concentrations of the NO precursor L
      arginine (3-10 mM) or the non-selective ET(A)/ET(B) endothelin receptor
      antagonist, Ro 47-0203 (10 microM). These data indicate that the NPY-induced
      effect does not involve either the endothelium-derived vasodilator nitric oxide
      or the vasoconstrictor endothelin. Conversely, in the presence of the cyclo
      oxygenase inhibitor, indomethacin (30 microM), NPY failed to potentiate the
      vasoconstrictions produced by either nerve stimulation or by exogenous NA, thus
      providing evidence that arachidonic acid metabolites through the cyclo-oxygenase
      pathway are mainly responsible for the potentiation evoked by NPY. 4. When the
      TxA2 receptor antagonists, Bay u 3405 (1 microM) and ifetroban (1 microM) were
      added to the superfusing medium, NPY did not alter either the frequency- or the
      concentration-response curves for either TNS or NA. Accordingly, both TNS- and NA
      induced contractions were not potentiated by NPY in the presence of the TxA2
      synthase inhibitor, UK 38485 (10 microM). This clearly demonstrates the pivotal
      role of TxA2 in NPY-induced potentiation. 5. In superfused vein rings with
      endothelium, a subthreshold concentration (0.2 nM) of the TxA2 mimetic U 46619
      potentiated both TNS- and NA-induced vasoconstrictions. This potentiation was
      higher at low stimulation frequencies and low NA concentrations, and resembled
      that produced by NPY. 6. Our results indicate that in the human saphenous vein
      NPY potentiates the contractions produced by sympathetic nerve stimulation acting
      at the postjunctional level, primarily on endothelial cells. In particular, the
      NPY-induced release of a cyclo-oxygenase metabolite, namely TxA2, may have a
      synergistic effect on the vasoconstriction induced by the noradrenergic mediator.
      Thus, such a mechanism may play a key role in the maintenance of the sympathetic
      tone of large human capacitance vessels.

PMID- 9630350
TI  - Inhibition of nitrergic neurotransmission in the bovine retractor penis muscle by
      an oxidant stress: effects of superoxide dismutase mimetics.
AB  - 1. A number of superoxide dismutase (SOD) mimetics were examined both
      biochemically for their ability to inhibit the superoxide-catalyzed reduction of
      cytochrome c and nitro blue tetrazolium, and functionally for their ability to
      mimic authentic Cu/Zn SOD in restoring nitrergic neurotransmission in bovine
      retractor penis (BRP) muscle following its inhibition by oxidant stress. 2. The
      SOD mimetics investigated were CuSO4, MnCl2, CuDIPS (copper [II]
      [diisopropylsalicylate]2), MnTBAP (manganese [III] tetrakis 4-benzoic acid
      porphyrin), MnTMPyP (manganese [III] tetrakis 1-methyl-4-pyridyl porphyrin
      pentachloride), tiron (4,5-dihydroxy-1,3-benzene disulphonic acid), PTIYO (4
      phenyl,2,2,5,5,-tetramethyl-3-imidazolin-1-yloxy-3-oxide) and tempol (4-hydroxy
      2,2,6,6-tetramethylpiperidine-N-oxyl). 3. The rank order of potency in inhibiting
      the reduction of cytochrome c was: CuSO4 > or = MnCl2 > or = CuDIPS > or =
      MnTMPyP > MnTBAP > tempol > or = tiron > PTIYO. 4. The requirement for EDTA (0.1
      mM) prevented assessment of the activity of CuSO4, MnCl2 and CuDIPS in the assay
      involving inhibition of reduction of nitro blue tetrazolium. However, the rank
      order of potency for those agents which could be examined (MnTMPyP > MnTBAP >
      tiron > or = tempol > PTIYO) was essentially similar to that seen in the
      cytochrome c assay. 5. Inhibition of endogenous Cu/Zn SOD with
      diethyldithiocarbamate (DETCA, 3 mM, 120 min) in BRP muscle strips, followed by
      addition of the superoxide anion generator, LY 83583 (1 microM), resulted in
      almost complete abolition of nitrergic relaxation (4 Hz, 10 s). 6. Authentic
      Cu/Zn SOD (1-300 u ml(-1)), CuSO4 (0.1-300 microM), MnCl2 (0.1-100 microM) and
      MnTMPyP (10-300 microM) each restored nitrergic transmission by around 50%.
      However, CuDIPS (0.1-30 microM), MnTBAP (0.1-100 microM), tempol (10 microM - 3
      mM), PTIYO (1-300 microM) and tiron (10 microM - 10 mM) all failed to restore
      nitrergic transmission. 7. The ability of MnTMPyP to restore nitrergic
      neurotransmission may therefore provide a lead in the development of SOD mimetics
      as therapeutic agents in the treatment of neuropathies associated with oxidant
      stress.

PMID- 9630351
TI  - Effects of calcium and potassium supplements on arterial tone in vitro in
      spontaneously hypertensive rats.
AB  - 1. Calcium and potassium intakes inversely correlate with blood pressure in
      experimental hypertension. Therefore, we examined the effects of calcium and
      potassium supplements alone and in combination on arterial tone in spontaneously
      hypertensive rats (SHR). Wistar-Kyoto (WKY) rats served as normotensive controls.
      Calcium and potassium contents in the control diet were both 1%, while those in
      supplemented chows were 3% and 3.5%, respectively. The sodium content of all
      diets was moderately elevated to 1.1%. 2. After 12 weeks of the study systolic
      blood pressures in SHR on high calcium and on high potassium diets were markedly
      lower (about 53 and 58 mmHg, respectively) than in hypertensive controls, while
      combined supplementation of these cations reduced blood pressure even further
      (about 69 mmHg). 3. Responses of mesenteric arterial rings in vitro were examined
      at the end of the study. Both high calcium and high potassium diets improved the
      impaired relaxation to acetylcholine (ACh) in SHR, while the combination of these
      supplements completely normalized this response. Cyclo-oxygenase inhibition by
      diclofenac augmented the relaxation to ACh in hypertensive controls but not in
      the other groups. Nevertheless, enhanced endothelium-mediated dilatation was
      still observed in the presence of diclofenac and the nitric oxide synthase
      inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) in all supplemented groups.
      Interestingly, additional blockade of Ca2+-activated K+ channels by
      tetraethylammonium abolished the improved relaxation to ACh in SHR on high
      calcium and on high potassium, but distinct responses were still observed in WKY
      rats and SHR on the combined supplement. 4. When hyperpolarization of smooth
      muscle was prevented by precontraction of the preparations with 50 mM KCl, only
      marginal differences were observed in the diclofenac and L-NAME-resistant
      relaxations to ACh between the study groups. Finally, endothelium-independent
      vasorelaxations of noradrenaline-precontracted rings to nitroprusside,
      isoprenaline and cromakalim were comparably augmented by all supplements. 5. In
      conclusion, the vascular mechanisms underlying the antihypertensive effect of
      high calcium and high potassium diets during moderately elevated sodium intake in
      SHR may involve enhanced arterial hyperpolarization, increased smooth muscle
      sensitivity to nitric oxide and decreased production of vasoconstrictor
      prostanoids. The administration of these cations in combination was more
      effective than either of them alone in reducing blood pressure and restoring
      arterial tone.

PMID- 9630352
TI  - Characterization of phosphodiesterase 4 in guinea-pig macrophages: multiple
      activities, association states and sensitivity to selective inhibitors.
AB  - 1. The cyclic AMP phosphodiesterases (PDE) in guinea-pig peritoneal macrophages
      were isolated, partially characterized and their role in regulating the cyclic
      AMP content in intact cells evaluated. 2. Differential centrifugation of
      macrophage lysates revealed that approximately 90% of the PDE activity was
      membrane-bound and exclusively hydrolyzed cyclic AMP. This activity was not
      removed by KCl (200 mM) but was readily solubilized by the non-ionic detergent,
      Triton X-100 (1% v/v). Greater than 80% of the hydrolytic activity was suppressed
      by the PDE4 inhibitors, R-rolipram and nitraquazone with IC50s of 240 and 540 nM,
      respectively. 3. Anion-exchange chromatography of the total protein extracted
      from macrophages resolved two major peaks of cyclic AMP PDE activity that were
      insensitive to cyclic GMP (10 microM), calmodulin (50 units plus 2 mM CaCl2) and
      a PDE3 inhibitor, SK&F 95654 (10 microM), but were markedly suppressed by RS
      rolipram (10 microM). The two peaks of PDE activity were arbitrarily designated
      CPPDE4alpha and CPPDE4beta with respect to the order from which they were eluted
      from the column where the prefix, CP, refers to the species, Cavia porcellus. 4.
      The hydrolysis of cyclic AMP catalyzed by CPPDE4alpha and CPPDE4beta conformed to
      Michaelis-Menten kinetic behaviour with similar K(m)s (13.4 and 6.4 microM,
      respectively). 5. Thermal denaturation of membrane-bound PDE4 at 50 degrees C
      followed bi-exponential kinetics with t1/2 values of 1.5 and 54.7 min for the
      first and second components, respectively. In contrast, CPPDE4alpha and
      CPPDE4beta each decayed mono-exponentially with significantly different
      thermostabilities (t1/2 = 2.77 and 1.15 min, respectively). 6. Gel filtration of
      CPPDE4beta separated two peaks of rolipram-sensitive PDE activity. The main peak
      eluted at a volume indicative of a approximately 180 kDa protein but was preceded
      by a much larger form of the enzyme that had an estimated weight of 750 kDa. Size
      exclusion chromatography of CPPDE4alpha resolved a broad peak of activity with
      molecular weights spanning 50 to 200 kDa. 7. Of ten PDE inhibitors examined, none
      distinguished CPPDE4alpha from CPPDE4beta with respect to their IC50 values or
      their rank order of potency. RS-rolipram acted as a purely competitive inhibitor
      of cyclic AMP hydrolysis with K(i)s of 2 microM and 1.5 microM for CPPDE4alpha
      and CPPDE4beta, respectively. In contrast to the membrane-associated enzyme(s), R
      rolipram and nitraquazone were 4 to 19 fold less potent as inhibitors of
      CPPDE4alpha and CPPDE4beta. 8. In intact macrophages, Ro 20-1724 and RS-rolipram
      potentiated isoprenaline-induced cyclic AMP accumulation under conditions where a
      PDE3 inhibitor, SK&F 94120, was essentially inactive. 9. These data demonstrate
      that the predominant cyclic AMP hydrolyzing activity in guinea-pig macrophages is
      a PDE4. Moreover, thermostability studies and size exclusion chromatography
      indicates the possible expression of two intrinsic, membrane-associated
      isoenzymes which can regulate the cyclic AMP content in intact cells. The finding
      that soluble and particulate forms of the same enzyme exhibit different
      sensitivities to rolipram and nitraquazone implies that PDE4 can change
      conformation. Finally, the identification of multiple molecular weight species of
      CPPDE4 suggests that this enzyme(s) might form multimeric complexes of variable
      association states.

PMID- 9630353
TI  - Evidence for a cyclic GMP-independent mechanism in the anti-platelet action of S
      nitrosoglutathione.
AB  - 1. We have measured the ability of a range of NO donor compounds to stimulate
      cyclic GMP accumulation and inhibit collagen-induced aggregation of human washed
      platelets. In addition, the rate of spontaneous release of NO from each donor has
      been measured spectrophotometrically by the oxidation of oxyhaemoglobin to
      methaemoglobin. The NO donors used were five s-nitrosothiol compounds: S
      nitrosoglutathione (GSNO), S-nitrosocysteine (cysNO), S-nitroso-N-acetyl-DL
      penicillamine (SNAP), S-nitroso-N-acetyl-cysteine (SNAC), S-nitrosohomocysteine
      (homocysNO), and two non-nitrosothiol compounds: diethylamine NONOate (DEANO) and
      sodium nitroprusside (SNP). 2. Using 10 microM of each donor compound, mean+/
      s.e.mean rate of NO release ranged from 0.04+/-0.001 nmol min(-1) (for SNP) to
      3.15+/-0.29 nmol min(-1) (for cysNO); cyclic GMP accumulation ranged from 0.43+/
      0.05 pmol per 10(8) platelets (for SNP) to 2.67+/-0.31 pmol per 10(8) platelets
      (for cysNO), and inhibition of platelet aggregation ranged from 40+/-6.4% (for
      SNP) to 90+/-3.8% (for SNAC). 3. There was a significant positive correlation
      between the rate of NO release and the ability of the different NO donors to
      stimulate intra-platelet cyclic GMP accumulation (r = 0.83; P = 0.02). However,
      no significant correlation was observed between the rate of NO release and the
      inhibition of platelet aggregation by the different NO donors (r= -0.17), nor was
      there a significant correlation between cyclic GMP accumulation and inhibition of
      aggregation by the different NO donor compounds (r = 0.34). 4. Comparison of the
      dose-response curves obtained with GSNO, DEANO and 8-bromo cyclic GMP showed
      DEANO to be the most potent stimulator of intraplatelet cyclic GMP accumulation
      (P < 0.001 vs both GSNO and 8-bromo cyclic GMP), but GSNO to be the most potent
      inhibitor of platelet aggregation (P < 0.01 vs DEANO, and P < 0.001 vs 8-bromo
      cyclic GMP). 5. The rate of NO release from GSNO, and its ability both to
      stimulate intra-platelet cyclic GMP accumulation and to inhibit platelet
      aggregation, were all significantly diminished by the copper (I) (Cu+) chelating
      agent bathocuproine disulphonic acid (BCS). In contrast, BCS had no effect on
      either the rate of NO release, or the anti-platelet action of the non
      nitrosothiol compound DEANO. 6. Cyclic GMP accumulation in response to GSNO (10(
      9) 10(-5) M) was undetectable following treatment of platelets with ODQ (100
      microM), a selective inhibitor of soluble guanylate cyclase. Despite this
      abolition of guanylate cyclase stimulation, GSNO retained some ability to inhibit
      aggregation, indicating the presence of a cyclic GMP-independent component in its
      anti-platelet action. However, this component was abolished following treatment
      of platelets with a combination of both ODQ and BCS, suggesting that Cu+ ions
      were required for the cyclic GMP-independent pathway to operate. 7. The cyclic
      GMP-independent action of GSNO, observed in ODQ-treated platelets, could not be
      explained by an increase in intra-platelet cyclic AMP. 8. The impermeable thiol
      modifying agent p-chloromercuriphenylsulphonic acid (CMPS) produced a
      concentration-dependent inhibition of aggregation of ODQ-treated platelets,
      accompanied by a progressive loss of detectable platelet surface thiol groups.
      Additional treatment with GSNO failed to increase the degree of aggregation
      inhibition, suggesting that a common pathway of thiol modification might be
      utilized by both GSNO and CMPS to elicit cyclic GMP-independent inhibition of
      platelet aggregation. 9. We conclude that NO donor compounds mediate inhibition
      of platelet aggregation by both cyclic GMP-dependent and -independent pathways.
      Cyclic GMP generation is related to the rate of spontaneous release of NO from
      the donor compound, but transfer of the NO signal to the cyclic GMP-independent
      pathway may depend upon a cellular system which involves both copper (I) (Cu+)
      ions and surface membrane thiol groups. The potent anti-platelet action of GSNO

PMID- 9630354
TI  - Involvement of K+ channel permeability changes in the L-NAME and indomethacin
      resistant part of adenosine-5'-O-(2-thiodiphosphate)-induced relaxation of
      pancreatic vascular bed.
AB  - 1. We have previously demonstrated that adenosine-5'-O-(2-thiodiphosphate)
      (ADPbetaS), a potent P2Y-purinoceptor agonist, relaxed pancreatic vasculature not
      only through prostacyclin (PGI2) and nitric oxide (NO) release from the
      endothelium but also through other mechanism(s). In this study, we investigated
      the effects of an inhibitor of the Na+/K+ pump, of ATP-sensitive K+ (K(ATP))
      channels and of small (SK(Ca)) or large (BK(Ca)) conductance Ca2+-activated K+
      channels. Experiments were performed at basal tone and during the inhibition of
      NO synthase and cyclo-oxygenase. 2. In control conditions, ADPbetaS (15 microM)
      induced an initial transient vasoconstriction followed by a progressive and
      sustained vasodilatation. In the presence of N(omega)-nitro-L-arginine methyl
      ester (L-NAME, 200 microM) the transient vasoconstriction was reversed into a one
      minute vasodilator effect, which was then followed by a progressive and sustained
      vasodilatation similar to that observed with ADPbetaS alone. The addition of
      indomethacin (10 microM) did not significantly modify the profile of ADPbetaS
      induced vasodilatation. 3. Ouabain (100 microM) decreased basal pancreatic flow
      rate and did not modify ADPbetaS-induced relaxation. This inhibitor of the Na+/K+
      pump increased the pancreatic vasoconstriction induced by L-NAME or by the co
      administration of L-NAME and indomethacin. Ouabain did not modify either the L
      NAME or the L-NAME/indomethacin resistant part of the ADPbetaS vasodilatation. 4.
      The K(ATP) inhibitor tolbutamide (185 microM) did not significantly modify basal
      pancreatic flow rate and ADPbetaS-induced relaxation. This inhibitor which did
      not change L-NAME-induced vasoconstriction, significantly diminished the L-NAME
      resistant part of ADPbetaS-induced vasodilatation. Tolbutamide intensified the
      vasoconstriction induced by the co-administration of L-NAME and indomethacin. In
      contrast, the L-NAME/indomethacin resistant part of ADPbetaS vasodilatation was
      not changed by the closure of K(ATP). 5. The SK(Ca) inhibitor apamin (0.1 microM)
      did not significantly change pancreatic vascular resistance whatever the
      experimental conditions (in the absence or in presence of L-NAME or L
      NAME/indomethacin). In the presence of L-NAME, the closure of SK(Ca) channels
      changed the one minute vasodilator effect of ADPbetaS into a potent
      vasoconstriction and thereafter modified only the beginning of the second part of
      the L-NAME-resistant part of the ADPbetaS-induced vasodilatation. In contrast,
      the L-NAME/indomethacin resistant part of ADPbetaS-induced relaxation remained
      unchanged in the presence of apamin. 6. Charybdotoxin (0.2 microM), an inhibitor
      of BK(Ca), increased pancreatic vascular resistance in the presence of L
      NAME/indomethacin. In the presence of L-NAME, the closure of BK(Ca) channels
      reversed the one minute vasodilator effect of ADPbetaS into a potent
      vasoconstriction and drastically diminished the sustained vasodilatation. In
      contrast the L-NAME/indomethacin resistant part of ADPbetaS-induced relaxation
      was not modified by the presence of charybdotoxin. Under L
      NAME/indomethacin/charybdotoxin/apamin infusions, ADPbetaS evoked a drastic and
      transient vasoconstriction reaching a maximum at the second minute, which was
      followed by a sustained increase in the flow rate throughout the ADPbetaS
      infusion. The maximal vasodilator effect of ADPbetaS observed was not modified by
      the addition of apamin. 7. The results suggest that the L-NAME-resistant
      relaxation induced by ADPbetaS in the pancreatic vascular bed involves activation
      of BK(Ca), K(ATP) and to a lesser extent of SK(Ca) channels, but the L
      NAME/indomethacin resistant part of ADPbetaS-induced relaxation is insensitive to
      the closure of K(ATP), SK(Ca) and BK(Ca) channels.

PMID- 9630355
TI  - P2Y1-receptors in human platelets which are pharmacologically distinct from
      P2Y(ADP)-receptors.
AB  - 1. In the present study we have classified the receptor(s) mediating increases in
      intracellular calcium concentration ([Ca2+]i) in human washed platelets and
      compared the pharmacological profile obtained with that observed in Jurkat cells,
      stably transfected with a bovine P2Y1-receptor. 2. The P2Y1-receptor antagonist,
      adenosine-3'-phosphate-5'-phosphate (A3P5P), competitively antagonized agonist
      responses in both Jurkat cells, and in platelets with similar affinities (pK(B)
      of 5.8 and 6.0, respectively). 3. The selective P2Y(ADP) antagonist, AR-C66096,
      exhibited partial agonism in the Jurkat cells with an affinity (pK(A)) of 4.9.
      This value is consistent with its known P2Y1-receptor activity. In platelets, AR
      C66096 at a concentration (0.1 microM) approximately 100 fold greater than its
      known P2Y(ADP) receptor affinity, had no effect on ADP-induced increases in
      [Ca2+]i. 4. The ability of adenine nucleotide analogues to elevate [Ca2+]i in the
      Jurkat cells was also determined. The rank order of agonist potency (p[A]50) was:
      2-MeSADP (8.3)>2-ClATP (7.8)>ADP (7.5)=2-MeSATP (7.4)>ATPgammaS (6.5)>ATP (6.2),
      with ATP appearing to be a partial agonist. 5. The same rank order of potency was
      observed when similar experiments were performed in platelets. However, the
      absolute potencies of all the agonists and the intrinsic activities of both
      ATPgammaS and ATP were lower in platelets. 6. The operational model of agonism
      was used to test whether the agonist concentration-effect profiles obtained in
      these two cell types could be explained on the basis of differences in receptor
      reserve. The analysis indicated that the data obtained in platelets closely
      resembled that predicted for a low density or poorly coupled P2Y1-receptor
      system. 7. The hypothesis that the observed partial agonist behaviour of ATP was
      the result of receptor activation by contaminating ADP with concomitant receptor
      blockade by ATP, was tested in the platelet system. This hypothesis was supported
      by a theoretical analysis, which yielded an affinity value for ATP similar to
      that obtained previously at P2Y1-receptors. 8. In summary, the results of this
      study indicate that human washed platelets contain P2Y1-receptors which mediate
      increases in [Ca2+]i and that this receptor population is pharmacologically
      distinct from P2Y(ADP)-receptors.

PMID- 9630356
TI  - Irreversible binding of a carbostyril-based agonist and antagonist to the beta
      adrenoceptor in DDT1 MF-2 cells and rat aorta.
AB  - 1. The chemoreactive ligands 5(2-(((1'-(4'
      isothiocyanatophenylamino)thiocarbonyl)-amino) -2-methylpropyl)amino-2
      hydroxypropoxy)-3,4-dihydrocarbostyril (DCITC) and 8-hydroxy-5(2-(((1'-(4'
      isothiocyanatophenylamino)thiocarbonyl+ ++)amino)-2-methylprop-2-yl)amino-1
      hydroxyethyl)-carbostyril++ + (HCITC) were synthesized and shown to be potent
      irreversible antagonist and agonist ligands, respectively, for the beta
      adrenoceptor in DDT1 MF-2 (DDT) cells and the rat isolated aorta. 2. In DDT cell
      membranes DCITC and HCITC inhibited (-)[125I]-iodocyanopindolol (CYP) binding to
      the beta-adrenoceptor with IC50 values of 1.1 and 18 nM, respectively. (-)
      Isoprenaline inhibited [125I]-CYP binding with an IC50 of 355 nM. Pretreatment of
      membranes with either chemoreactive ligand produced a time- and concentration
      dependent decrease in the beta-adrenoceptor content, indicating irreversible
      receptor binding. DCITC at concentrations up to 10 microM did not stimulate
      cyclic AMP accumulation in DDT cells nor did it amplify forskolin-stimulated
      cyclic AMP accumulation. 3. In the rat isolated aorta, DCITC (0.1 microM) did not
      affect either the phenylephrine-mediated tissue contraction or the acetylcholine
      mediated relaxation. DCITC attenuated the maximal (-)-isoprenaline-mediated
      relaxation of a phenylephrine contracted aorta in a concentration-dependent
      manner and shifted the dose-response curves for (-)-isoprenaline to the right.
      The DCITC-induced decrease in maximal response was not reversed by extensive
      tissue washing. By use of the operational model of agonism, the calculated
      dissociation constant for (-)-isoprenaline ws 286 nM and the estimated receptor
      reserve for this agonist was 23% at the maximal response. 4. HCITC and (-)
      isoprenaline stimulated cyclic AMP accumulation in DDT cells with pD2 values
      (negative logarithm to base 10 of EC50) of 7.95 and 7.97, respectively, and both
      mediated the same maximal stimulation. In the rat isolated aorta, HCITC produced
      a concentration-dependent relaxation of the tissue with a pD2 value of 6.62,
      whereas the pD2 for (-)-isoprenaline was 7.03. However, HCITC produced a greater
      maximal relaxation of the tissue than (-)-isoprenaline. The HCITC-mediated
      stimulation of cyclic AMP accumulation and relaxation of the isolated tissue were
      blocked when the beta-antagonist propranolol was added concurrently. In contrast,
      once the HCITC-mediated responses were established, the addition of propranolol
      did not result in any attenuation indicating that HCITC is an irreversible beta
      agonist.

PMID- 9630357
TI  - Pharmacological properties of P2X3-receptors present in neurones of the rat
      dorsal root ganglia.
AB  - 1. The electrophysiological actions of several agonists which may differentiate
      between P2X1- and P2X3-receptors were studied under concentration and voltage
      clamp conditions in dissociated neurones of 1-4 day old rat dorsal root ganglia.
      2. Beta,gamma-Methylene-D-ATP (beta,gamma-me-D-ATP) (1-300 microM), diadenosine
      5',5'''-P1,P5-pentaphosphate (AP5A) (100 nM - 300 microM), diadenosine 5',5'''
      P1,P4-tetraphosphate (AP4A) (300 nM - 300 microM) and uridine 5'-triphosphate
      (UTP) (1 microM - 1 mM) all activated concentration-dependent inward currents
      with a latency to onset of a few ms. 3. The concentration-response curves for
      beta,gamma-me-D-ATP and AP5A and ATP had similar maximum values, while that for
      AP4A had a lower maximum. The concentration-response curve to UTP was shallow and
      did not reach a maximum. Beta,gamma-Methylene-L-ATP was virtually inactive. The
      rank order of agonist potency was ATP > AP5A approximately AP4A > beta,gamma-me-D
      ATP > UTP > > beta,gamma-methylene-L-ATP. 4. The inward currents were inhibited
      by the P2-receptor antagonists suramin (100 microM) and pyridoxalphosphate-6
      azophenyl-2',4'-disulphonic acid (PPADS) (10 microM). PPADS also inhibited
      responses to ATP (800 nM) and alpha,beta-methylene ATP (2 microM) in a
      concentration-dependent manner. 5. This study shows that beta,gamma-me-D-ATP,
      AP5A, AP4A and UTP all act via a suramin- and PPADS-sensitive P2X-receptor to
      evoke rapid, transient inward currents in dissociated neurones of rat dorsal root
      ganglia. The very low activity of beta,gamma-methylene-L-ATP suggests that the
      agonists were acting at the P2X3-subtype to produce these effects.

PMID- 9630358
TI  - Endothelium-dependent relaxation and hyperpolarization in guinea-pig coronary
      artery: role of epoxyeicosatrienoic acid.
AB  - 1. Acetylcholine (ACh) elicits an endothelium-dependent relaxation and
      hyperpolarization in the absence of nitric oxide (NO) and prostaglandin synthesis
      in the guinea-pig coronary artery (GPCA). This response has been attributed to a
      factor termed endothelial-derived hyperpolarizing factor (EDHF). Recently it has
      been suggested that EDHF may be a cytochrome P450 product of arachidonic acid
      (AA) i.e., an epoxyeicosatrienoic acid (EET). The present study investigated
      whether this pathway could account for the response to ACh observed in the GPCA
      in the presence of 100 microM N(omega)-nitro-L-arginine and 10 microM
      indomethacin. 2. ACh, AA and 11,12-EET each produced concentration-dependent
      relaxations in arteries contracted with the H1-receptor agonist AEP (2,2
      aminoethylpyridine). The AA-induced relaxation was significantly enhanced in the
      presence of the cyclo-oxygenase/lipoxygenase inhibitor, eicosatetranynoic acid
      (30 microM). 3. The cytochrome P450 inhibitors proadifen (10 microM) and
      clotrimazole (10 microM) inhibited ACh, lemakalim (LEM) and AA-induced
      relaxation, whereas 17-octadecynoic acid (100 microM) and 7-ethoxyresorufin (10
      microM) were without effect on all three vasodilators. Proadifen and clotrimazole
      also inhibited ACh (1 microM) and LEM (1 microM)-induced hyperpolarization. 4.
      The ability of various potassium channel blockers to inhibit relaxation responses
      elicited with ACh, AA and 11,12-EET was also determined. Iberiotoxin (IBTX; 100
      nM) was without effect on responses to ACh but significantly reduced responses to
      both AA and 11,12-EET. In contrast, 4-aminopyridine (4-AP; 5 mM) significantly
      reduced response to ACh but not responses to AA and 11,12-EET. Combined IBTX plus
      (4-AP) inhibited the ACh-induced relaxation to a greater extent than 4-AP alone.
      Apamin (1 microM), glibenclamide (10 microM) and BaCl2 (50 microM) had no
      significant effect on responses to ACh, AA and 11,12-EET. 5. IBTX (100 nM)
      significantly reduced both 11,12-EET (33 microM) and AA (30 microM)
      hyperpolarization without affecting the ACh (1 microM)-induced hyperpolarization.
      In contrast, 4-AP significantly reduced the ACh-induced hyperpolarization without
      affecting either AA or 11,12-EET-induced hyperpolarizations. 6. In summary, our
      results suggest that the coronary endothelium releases a factor upon application
      of AA which hyperpolarizes the smooth muscle. The similarity of pharmacology
      between AA and 11,12-EET suggests that this factor is an EET. However, the
      disparity of pharmacology between responses to ACh versus responses to 11,12-EET
      do not support the hypothesis that EETs represent the predominant factor which
      ACh releases from the endothelium that leads to NO- and prostaglandin-independent
      hyperpolarization and relaxation in the GPCA.

PMID- 9630359
TI  - Ovalbumin-induced neurogenic inflammation in the bladder of sensitized rats.
AB  - 1. We have developed and characterized a model of immediate
      hypersensitivity/inflammation of the urinary bladder in vivo induced by local
      application of ovalbumin (OA) in OA- sensitive female rats. Two parameters of the
      inflammatory response were assessed following OA challenge: plasma protein
      extravasation (PPE) and changes in smooth muscle reactivity. The former was
      estimated by measurement of Evans blue extravasation at 0.5, 2, 4, 8 and 24 h
      time point following in vivo challenge. Changes in reactivity were determined by
      measurement of isotonic tension responses of urinary bladder strips following OA
      challenge in vitro. 2. Acute in vivo intravesical OA challenge (10 mg in 0.3 ml
      saline) in actively sensitized female Wistar rats caused a time-dependent PPE in
      the urinary bladder which was biphasic with peak responses at 2-4 and 24 h. 3.
      The PPE response to acute OA challenge, above base-line, at 2 h was abolished by
      systemic capsaicin pretreatment (50 mg kg(-1), s.c., 4 days before use) (P <
      0.05) whilst the response at 24 h was unaffected. The 2 h time point was then
      used for further studies. 4. Degranulation of mast cells, achieved by
      pretreatment with compound 48/80 (5 mg kg(-1), s.c. for 3 consecutive days),
      completely abolished the PPE response to OA challenge at the 2 h time point. 5.
      The tachykinin NK1 receptor antagonist, SR 140333 (0.1 micromol kg(-1), i.v.),
      abolished the 2 h PPE response whilst the tachykinin NK2 receptor antagonist MEN
      11420 (0.1 micromol kg(-1), i.v.) appeared to reduce the response by
      approximately 50% but this did not reach significance. The bradykinin B2 receptor
      antagonist, Hoe 140 (0.1 micromol kg(-1), i.v.), similarly to SR 140333, blocked
      the 2 h PPE response to OA, whereas the selective B1 receptor antagonist B 9858
      (0.1 micromol kg(-1), i.v.) had no significant effect. Inhibition of cyclo
      oxygenase (COX) achieved by pretreatment with the COX inhibitor dexketoprofen
      (5.3 micromol kg(-1), i.v.) also blocked the PPE response, whilst the leukotriene
      receptor antagonist ONO 1078 (1 micromol kg(-1), i.v.) significantly reduced PPE
      by about 80%. 6. In the rat isolated urinary bladder OA (1 mg ml(-1)) challenge
      produced a biphasic response with a rapidly achieved maximal contraction followed
      by a sustained contraction for approximately 25 min. In vitro capsaicin
      pretreatment (10 microM for 15 min) significantly attenuated the duration of the
      sustained contraction whilst having no effect on the maximum contractile response
      achieved. In vivo pretreatment of animals with compound 48/80 significantly
      attenuated (42%) the maximum contractile response. Combination of both treatments
      almost completely abolished the response. In vitro treatment with Hoe 140 (1
      microM) had no significant effect on the response to OA and neither did ONO 1078
      (1 microM). 7. These results show that both the early inflammatory response and
      alterations in smooth muscle reactivity to OA challenge in actively sensitized
      animals are dependent on mast cell degranulation and the activation of sensory C
      fibres. Furthermore this model of allergic cystitis may be useful for
      investigating both the processes involved and potential novel therapies in the
      treatment of interstitial cystitis.

PMID- 9630360
TI  - Effect of chronic bradykinin B2 receptor blockade on blood pressure of conscious
      Dahl salt-resistant rats.
AB  - 1. In this study 3 protocols were utilized to determine the role of endogenous
      kinins in the resistance of the inbred Dahl (Rapp) salt-resistant (SR/Jr) rats to
      high salt diet-induced blood pressure elevation. 2. The bradykinin B2 receptor
      antagonist, Hoe 140 (D-Arg[Hyp3, Thi5, D-Tic7, Oic8]-bradykinin) at doses of
      either 10-20 or 20-40 nmol day(-1) (subcutaneously (s.c), via osmotic minipumps,
      for either 1 or 3 weeks during a high (8%) salt diet) effectively blocked or
      attenuated the hypotensive responses to 100-1000 ng of bradykinin. 3. In the
      first protocol, 5 week old SR/Jr rats treated with Hoe 140 (10-20 nmol day(-1), n
      = 9, s.c., via osmotic minipumps) for 3 weeks and concomitantly fed high (8%)
      NaCl diet had significantly higher conscious tail cuff blood pressures (BPc) at 1
      and 3 weeks when compared with rats treated with vehicle (0.9% NaCl, n = 6). The
      differences in BPc between the 2 groups were 13 mmHg (P < 0.001) after 1 week and
      8 mmHg (P < 0.05) after 3 weeks of treatment. 4. In the second protocol, 5 week
      old SR/Jr rats were treated with Hoe 140 (20-40 nmol day(-1), n = 8, s.c., via
      osmotic minipumps) or vehicle (n = 8) for 3 weeks. During the first week of
      treatment the rats were fed normal (0.8%) NaCl diet. The rats were then switched
      to 8% NaCl for 2 remaining weeks of the protocol. The mean BPc of Hoe 140-treated
      rats was not significantly different from that of the vehicle-treated rats when
      fed 0.8% NaCl diet. In contrast, rats treated with Hoe 140 and concomitantly fed
      high (8%) NaCl diet had significantly increased BPc (123+/-2 vs 111 +/- 1 mmHg, P
      < 0.001 for the Hoe 140- and vehicle-treated rats, respectively). 5. In the third
      protocol, treatment with Hoe 140 (20 40 nmol day(-1), s.c., via osmotic
      minipumps) during high salt diet did not increase BPc in rats that were pre
      exposed to the high salt diet for 2 weeks. 6. At the end of 3 weeks of study,
      blood pressure was measured via an arterial catheter during pentobarbitone
      induced anaesthesia. Rats treated with Hoe 140 for 1 or 3 weeks had significantly
      lower mean arterial blood pressures than the vehicle-treated rats. 7. Our
      findings suggest that in SR/Jr rats, kinin activation of bradykinin B2 receptors
      at least partially contributes to early regulatory mechanisms that resist an
      increase in blood pressure following exposure to a high salt diet. The mechanism
      underlying the decreased blood pressure during pentobarbitone anaesthesia of
      SR/Jr rats chronically treated with Hoe 140 has yet to be elucidated.

PMID- 9630361
TI  - Electrophysiological and neurochemical evidence that pindolol has agonist
      properties at the 5-HT1A autoreceptor in vivo.
AB  - 1. It has been hypothesized that 5-HT1A autoreceptor antagonists may enhance the
      therapeutic efficacy of SSRIs and other antidepressants. Although early clinical
      trials with the beta-adrenoceptor/5-HT1 ligand, pindolol, were promising, the
      results of recent more extensive trials have been contradictory. Here we
      investigated the actions of pindolol at the 5-HT1A autoreceptor by measuring its
      effect on 5-HT neuronal activity and release in the anaesthetized rat. 2.
      Pindolol inhibited the electrical activity of 5-HT neurones in the dorsal raphe
      nucleus (DRN). This effect was observed in the majority of neurones tested
      (10/16), was dose-related (0.2-1.0 mg kg(-1), i.v.), and was reversed by the 5
      HT1A receptor antagonist, WAY 100635 (0.1 mg kg(-1), i.v.), in 6/7 cases tested.
      3. Pindolol also inhibited 5-HT neuronal activity when applied
      microiontophoretically into the DRN in 9/10 neurones tested. This effect of
      pindolol was current-dependent and blocked by co-application of WAY 100635 (3/3
      neurones tested). 4. In microdialysis experiments. pindolol caused a dose-related
      (0.8 and 4 mg kg(-1), i.v.) fall in 5-HT levels in dialysates from the frontal
      cortex (under conditions where the perfusion medium contained 1 microM
      citalopram). In rats pretreated with WAY 100635 (0.1 mg kg(-1), i.v.), pindolol
      (4 mg kg(-1), i.v.) did not decrease, but rather increased 5-HT levels. 5. We
      conclude that, under the experimental conditions used in this study, pindolol
      displays agonist effects at the 5-HT1A autoreceptor. These data are relevant to
      previous and ongoing clinical trials of pindolol in depression which are based on
      the rationale that the drug is an effective 5-HT1A autoreceptor antagonist.

PMID- 9630362
TI  - Molecular cloning, expression and characterization of cDNA encoding a mouse
      alpha1a-adrenoceptor.
AB  - 1. In this study, we have cloned, expressed, and characterized an alpha1a
      adrenoceptor gene from the mouse. We designed oligonucleotide PCR primers
      complementary to regions of the rat alpha1a-adrenoceptor sequence and amplified
      cDNA fragments from total RNA of mouse cerebral cortex, liver and kidney by
      reverse transcription-polymerase chain reaction (RT PCR). 2. Both the nucleotide
      and deduced peptide sequences of the cDNA showed high sequence identity with
      those of cloned alpha1a-adrenoceptors from other species. The cDNA clone had an
      open reading frame of 1398 nucleotides encoding a 466 amino acid peptide which
      had 97%, 92% and 90% identity with the deduced amino acid sequences of the rat,
      human and bovine alpha1a-adrenoceptor, respectively. 3. The amplified mouse cDNA
      was inserted into a mammalian expression vector pcDNA3.1(+) and expressed in COS
      1 cells. The pharmacological properties of the mouse cDNA clone were examined in
      radioligand binding studies and functional assays. The expressed mouse protein
      had a high affinity for [3H]-prazosin (Kd = 0.48 nM) and pattern of affinity for
      antagonists in competition studies that is similar to that of the rat alpha1a
      adrenoceptor. Chloroethylclonidine (CEC) could slowly alkylate the expressed
      protein, with a rate similar to that of the rat alpha1a-adrenoceptor. 4. The
      expressed receptors were able to mediate noradrenaline (NA) stimulation of the
      production of inositol phosphates in COS-1 cells, consistent with coupling to
      phospholipase C. This response to NA could be reversed by pretreatment of the
      transfected cells with prazosin. 5. Based on the above evidence, we concluded
      that the cloned cDNA is that of the mouse alpha1a-adrenoceptor.

PMID- 9630363
TI  - Responses to endothelium-dependent agonists in subcutaneous arteries excised from
      hypercholesterolaemic men.
AB  - 1. Vasomotor function of the vascular endothelium was examined in human
      subcutaneous arteries excised from 8 hypercholesterolaemic and 7 normolipidaemic
      subjects. 2. Left gluteal skin biopsies were performed under local anaesthesia.
      Subcutaneous arteries were isolated and two vessels from each subject mounted in
      separate myographs. A 20 ml fasting blood sample was taken at the time of the
      biopsy. 3. Hypercholesterolaemic subjects had either never been treated with
      lipid lowering therapy or therapy had been stopped at least two weeks before the
      study (n = 2). At the time of the study total plasma cholesterol levels (control:
      4.6+/-0.3 vs hypercholesterolaemic: 8.3+/-0.6 mmol l(-1): P < 0.01) were
      significantly elevated in hypercholesterolaemic subjects when compared with
      controls. 4. Full concentration-response curves to the vasoconstrictor
      noradrenaline and the vasodilators acetylcholine and substance P were
      constructed. A single point concentration-response to sodium nitroprusside (10
      microM) was also obtained. Dilator responses were obtained in vessels pre
      constricted with a submaximal concentration of noradrenaline. Vessels were then
      incubated for 30 min with either L- or D-arginine (10 microM) and the
      concentration-response curves to the three dilator agonists repeated in the
      presence of the amino acid. 5. Maximum relaxation responses to acetylcholine
      (control vs hypercholesterolaemic: 83.3+/-6.1% vs 47.4+/-13.5%; P < 0.05), but
      not to substance P or sodium nitroprusside, were dampened in the
      hypercholesterolaemic group when compared with controls. 6. Neither incubation
      with L-arginine nor D-arginine had any effect on maximum relaxation responses to
      acetylcholine in either the control group (pre L-arginine vs plus L-arginine:
      83.3+/-6.1 vs 82.3+/-5.5%, pre D-arginine vs plus D-arginine: 98.9+/-1.2 vs
      98.2+/-1.1%) or the hypercholesterolaemic group (pre L-arginine vs plus L
      arginine: 47.4+/-13.5 vs 55.3+/-14.3%, pre D-arginine vs plus D-arginine: 43.3+/
      13.6 vs 65.4+/-12.3%). 7. When results from the two study groups were pooled, the
      strongest predictor of maximum relaxation obtained to acetylcholine was
      apolipoprotein A1 (r = 0.67; P = 0.001). 8. In conclusion, relaxation responses
      mediated by the endothelium-dependent agonist acetylcholine, but not by substance
      P, are impaired in hypercholesterolaemic patients. L-Arginine did not improve the
      impaired relaxation responses to acetylcholine. We suggest that impaired
      endothelium-dependent relaxation is specific to acetylcholine and not to an
      abnormal L-arginine-nitric oxide pathway in subcutaneous arteries excised from
      this study group.

PMID- 9630365
TI  - Interaction between superoxide anion and nitric oxide in the regulation of
      vascular endothelial function.
AB  - 1. Nitric oxide (NO)-mediated, endothelium-dependent vasodilator function in rat
      aortic smooth muscle was investigated in an in vitro model of endogenous vascular
      superoxide anion stress, generated by pretreatment with the Cu/Zn superoxide
      dismutase (SOD, EC 1.15.1.1) inhibitor, diethyldithiocarbamate (DETCA). 2.
      Contraction to noradrenaline (NA, 1 nM - 1 microM) in endothelium-intact vessels
      was augmented after a 30 min pretreatment with DETCA (10 mM) followed by 30 min
      washout. This effect was abolished by N(G)-nitro-L-arginine methyl ester (L-NAME,
      0.3 mM) and removal of the endothelium and partially reversed by exogenous Cu/Zn
      SOD (200 u ml(-1)). 3. Endothelium- and basal NO-dependent vasorelaxation to the
      phosphodiesterase (PDE) type V inhibitor ONO- 1 505 (4-[2-(2
      hydroxyethoxy)ethylamino]-2-(1H-imidazol-1-yl)-6-methoxyquin azoline
      methanesulphonate) (0.1-10 microM) was inhibited after DETCA (10 mM)
      pretreatment. In addition, the ability of L-NAME (0.3 mM) to enhance established
      contractile tone was effectively absent. 4. In contrast, DETCA pretreatment did
      not significantly affect vasorelaxation to acetylcholine (ACh, 1 nM - 3 microM)
      or S-nitroso-N-acetyl penicillamine (SNAP, 0.03-30 microM). However, L-NAME (0.3
      mM) unmasked an inhibitory effect of DETCA pretreatment on vasorelaxation to SNAP
      in endothelium-intact vessels while markedly potentiating vasorelaxation to SNAP
      in control tissue. 5. L-NAME (0.3 mM)- and exogenous catalase (200 u ml(-1))
      sensitive vasorelaxation to exogenous Cu/ Zn SOD (200 u ml(-1)) was greater after
      DETCA (10 mM) pretreatment in endothelium-intact aortic rings. This difference
      was abolished by catalase (200 u ml(-1)). 6. In conclusion, tissue Cu/Zn SOD
      inhibition elicited a selective lesion in basal endothelial function in rat
      isolated aortic smooth muscle, consistent with the inactivation of basal NO by
      superoxide anion. The resulting leftward shift in nitrovasodilator reactivity,
      due to the loss of the tonic depression by basal NO, is likely to mask the
      inhibitory effect of superoxide anion on agonist-stimulated endothelial function
      and nitrovasodilator-derived NO, thereby accounting for the differential pattern
      of endothelial dysfunction after DETCA pretreatment.

PMID- 9630364
TI  - Modulation of cell adhesion molecule expression and function on human lung
      microvascular endothelial cells by inhibition of phosphodiesterases 3 and 4.
AB  - 1. Expression of cell adhesion molecules (CAM) on the lung microvascular
      endothelium is believed to play a key role in the recruitment of leukocytes in
      pulmonary inflammation. Moreover, regulation of CAM expression may be an
      important mechanism through which this inflammation may be controlled.
      Experimental evidence has suggested that combined phosphodiesterase (PDE) 3 and 4
      inhibitors increase cyclic AMP levels within cells greater than inhibition of
      either isoenzyme alone. In the present study we assessed the effect of
      combinations of rolipram (PDE4 inhibitor), ORG 9935 (PDE3 inhibitor) and
      salbutamol (beta-agonist) on CAM expression and neutrophil or eosinophil adhesion
      to human lung microvascular endothelial cells (HLMVEC). 2. Tumour necrosis factor
      alpha (TNF-alpha)-induced intercellular adhesion molecule (ICAM)-1, vascular cell
      adhesion molecule (VCAM)-1 and E-selectin expression were measured on HLMVEC
      monolayers at 6 h by a specific ELISA technique in the presence of different
      combinations of medium, rolipram, ORG 9935 and salbutamol. 3. Rolipram in
      combination with salbutamol, but neither agent alone, inhibited TNF-alpha-induced
      E-selectin expression, whilst ICAM-1 and VCAM-1 expression were not affected. ORG
      9935 had no significant effect on CAM expression alone. However, in combination
      with rolipram a syngergistic inhibition of VCAM-1 and E-selectin, but not ICAM-1,
      expression was observed. No further inhibition was seen in the additional
      presence of salbutamol. 4. Neutrophil adhesion to TNF-alpha-stimulated (6 h)
      HLMVEC was mainly E-selectin dependent in this model, as ENA2 an anti-E-selectin
      monoclonal antibody (mAb) abrogated neutrophil adhesion. Eosinophil adhesion was
      E-selectin-, ICAM-1- and VCAM-1-dependent, as assessed by the inhibitory activity
      of ENA2 and the ability of a mAb to the ICAM-1 ligand, CD18, and a mAb to the
      VCAM-1 ligand, VLA4, to attenuate adhesion. 5. Rolipram in the presence of
      salbutamol or ORG 9935 significantly inhibited neutrophil adherence to TNF-alpha
      stimulated HLMVEC. Eosinophil adherence to monolayers was inhibited only when
      HLMVEC were activated in the presence of rolipram and ORG 9935. 6. Collectively,
      the findings presented in this manuscript suggest that inhibition of PDE4 with
      appropriate activation of adenylate cyclase is sufficient to inhibit induction of
      E-selectin expression on HLMVEC to a level that has functional consequences for
      neutrophil adhesion. In contrast, combined inhibition of PDE3 and 4 isoenzymes is
      necessary to inhibit VCAM-1 and to have inhibitory effects on eosinophil adhesion
      to activated HLMVEC. Upregulation of ICAM-1 expression on HLMVEC does not appear
      to be modulated by PDE3 and 4 inhibition. These data may have implications for
      the use of selective PDE4 inhibitors in lung inflammation.

PMID- 9630366
TI  - Dual effects of dichloroacetate on cardiac ischaemic preconditioning in the rat
      isolated perfused heart.
AB  - 1. Ischaemic cardiac preconditioning represents an important cardioprotective
      mechanism which limits myocardial ischaemic damage. The aim of this investigation
      was to assess the impact of dichloroacetate (DCA), a pyruvate dehydrogenase
      complex activator, on preconditioning. 2. Rat isolated hearts were perfused by
      use of the Langendorff technique, and were subjected to either preconditioning (3
      x 4 or 3 x 6 min ischaemia) or continuous perfusion, followed by 30 min global
      ischaemia and 60 min reperfusion. DCA (3 mM) was either given throughout the
      protocol (pretreatment), during reperfusion only (post-treatment), or not at all.
      Throughout reperfusion mechanical performance was assessed as the rate-pressure
      product (RPP: left ventricular developed pressure x heart rate). 3. In non
      preconditioned control hearts, mechanical performance was substantially (P <
      0.001) depressed on reperfusion (the RPP after 60 min of reperfusion (RPP(t=60))
      was 4,246+/-974 mmHg beats min(-1) compared to baseline value of 21,297+/-1,728
      mmHg beats min(-1)). Preconditioning with either 3 x 4 min or 3 x 6 min cycles
      caused significant protection, as shown by enhanced recovery (RPP(t=60) = 7,818+/
      1,138, P < 0.05, and 11,123+/-587 mmHg beats min(-1), P < 0.001, respectively).
      4. Addition of DCA (3 mM) to hearts under baseline conditions significantly (P <
      0.001) enhanced systolic function with an increased left ventricular developed
      pressure of 108+/-5 mmHg compared to 88.3+/-3.0 mmHg in the controls. 5.
      Pretreatment with 3 mM DCA had no effect on recovery of mechanical performance in
      the non-preconditioned hearts (RPP(t=60) = 3,640+/-1,235 mmHg beats min(-1))
      while the beneficial effects of preconditioning were reduced in the
      preconditioned hearts (3 x 4 min: RPP(t=60) = 2,919+/-1,060 mmHg beats min(-1); 3
      x 6 min: RPP(t=60) = 8,032+/-1,367 mmHg beats min(-1)). Therefore, DCA had
      increased the threshold for preconditioning. 6. By contrast, post-treatment of
      hearts with 3 mM DCA substantially improved recovery on reperfusion in all groups
      (RPP(t=60) = 5,827+/-1,328 (non-preconditioned), 14,022+/-3,743 (3 x 4 min; P <
      0.01) and 23,219+/-1,374 (3 x 6 min; P < 0.001) mmHg beats min(-1)). 7. The
      results of the present investigation clearly show that pretreatment with DCA
      enhances baseline cardiac mechanical performance but increases the threshold for
      cardiac preconditioning. However, post-treatment with DCA substantially augments
      the beneficial effects of preconditioning.

PMID- 9630367
TI  - Outward current produced by somatostatin (SRIF) in rat anterior cingulate
      pyramidal cells in vitro.
AB  - 1. A high density of receptors for somatostatin (SRIF) exists in the anterior
      cingulate cortex but their function is unknown. Whole-cell patch clamp recordings
      were made from visualized deep layer pyramidal cells of the rat anterior
      cingulate cortex contained in isolated brain slices to investigate the putative
      effects of SRIF and to identify the receptor subtype(s) involved. 2. SRIF (1-1000
      nM) produced a concentration-dependent outward current which was associated with
      an increased membrane conductance, was sensitive to Ba2+ (300 microM - 1 mM), and
      was absent in the presence of a maximal concentration of the GABA(B) receptor
      agonist, baclofen (100 microM). These observations suggest the outward current
      was carried by K+ ions. 3. SRIF analogues also elicited outward currents with a
      rank potency order of (EC50, nM): octreotide (1.8)>BIM-23027 (3.7)>SRIF (20)=L
      362,855 (20). BIM-23056 was without agonist or antagonist activity. Responses to
      L-362,855 were unlike those to the other agonists since they were sustained for
      the duration of the application. 4. The sst2 receptor antagonist, L-Tyr8Cyanamid
      154806 (1 microM), had no effect alone but partially reversed responses to
      submaximal concentrations of SRIF (100 nM, 44+/-6% reversal) and L-362,855 (100
      nM, 70+/-6% reversal) and fully reversed the response to BIM-23027 (10 nM). In
      contrast, L-Tyr8Cyanamid 154806 did not antagonize the response to baclofen (10
      microM). 5. We conclude that SRIF activates a K+ conductance in anterior
      cingulate pyramidal neurones via an action predominantly at sst2 receptors.

PMID- 9630368
TI  - Clostridium difficile--setting the scene.

PMID- 9630369
TI  - Clinical impact and associated costs of Clostridium difficile-associated disease.
AB  - Toxin-producing Clostridium difficile is the commonest cause of nosocomial
      diarrhoea and, as such, poses a major problem in our hospitals. The main
      population susceptible to disease is the elderly, for reasons that remain
      unclear. By contrast, carriage rates in neonates are high, but disease is low.
      The organism also has a major clinical impact in the immunosuppressed host,
      patients undergoing surgery (especially gastrointestinal) and those with severe
      underlying disease and longer hospital stay. Other interventions with high-risk
      associations are enemas, nasogastric and gastrostomy tubes and anti-peristaltic
      drugs. Data on the associated costs of C. difficile diarrhoea are not freely
      available, but one estimate is that in an average-sized district general
      hospital, 100 cases of C. difficile infection can be expected each year with an
      extra annual cost of 400,000 pound sterling and 2100 lost bed days.

PMID- 9630370
TI  - Pathogenesis of Clostridium difficile infection.
AB  - Clostridium difficile produces two major toxins referred to as toxins A and B.
      These are thought to be primarily responsible for the virulence of the bacterium
      and the major contributors to the pathogenesis of antibiotic-associated
      gastrointestinal disease. The molecular organization and control of expression of
      toxins A and B is now starting to be understood, and the cellular mechanism of
      action of both toxins, glucosylation of Rho family proteins, has been discovered.
      Other factors, such as production of proteolytic and hydrolytic enzymes,
      expression of fimbriae and flagella, chemotaxis and adhesion to gut receptors,
      and production of capsule, may all play a part in pathogenesis by facilitating
      colonization or by directly contributing to tissue damage, or both. Differential
      expression between strains of various combinations of these colonization and
      virulence factors may explain the apparent variability in virulence of C.
      difficile strains.

PMID- 9630371
TI  - The role of antimicrobial agents in the aetiology of Clostridium difficile
      associated disease.
AB  - High Clostridium difficile disease rates were originally associated with
      clindamycin use, but this association has declined in recent years following the
      decline in the clinical use of clindamycin, and disease is now particularly
      associated with the use of broad-spectrum antibiotics, especially the
      cephalosporins. There are now sufficient reports in the literature to merit the
      discontinuation of the widespread use of cephalosporins, especially in the
      elderly, by the substitution, wherever possible, with antibiotics not associated
      with the promotion of C. difficile-associated disease. Such agents include
      benzylpenicillin, gentamicin, trimethoprim, ciprofloxacin and the ureido
      penicillins. Widespread education about the proper use of antibiotics in clinical
      practice remains essential.

PMID- 9630372
TI  - The diagnosis of Clostridium difficile-associated disease.
AB  - There are well-documented risk factors associated with the development of
      antibiotic-associated diarrhoea; knowledge of these and of the typical signs and
      symptoms should alert the clinician to the possibility of Clostridium difficile
      associated diarrhoea (CDAD). It is therefore common practice in large general
      hospitals for clinicians to request, and for laboratories to include,
      investigations for C. difficile on in-patient stool specimens to confirm a
      diagnosis of CDAD. The laboratory methods used to investigate for CDAD are
      divided into two main categories: those that are aimed at detecting the presence
      of C. difficile or its products, and those that detect either of its two major
      toxins, A (enterotoxin) and B (cytotoxin). Within each of these broad strategies
      there are various rationales which are reviewed here.

PMID- 9630373
TI  - Treatment of Clostridium difficile infection.
AB  - The treatment options for Clostridium difficile infection remain limited,
      although promising agents are currently being assessed. Metronidazole is the
      first-line drug of choice for those patients requiring specific anti-C. difficile
      treatment. Much of the interest in alternative therapies has centred on the
      difficult management issues posed by patients with multiple symptomatic
      recurrences of C. difficile infection. However, it is now clear that the majority
      of these episodes are due to reinfections with new C. difficile strains and not
      relapses caused by the original bacterium. Hence, the true efficacy of the
      alternative regimens remains unclear. Individuals susceptible to C. difficile
      reinfections need to be protected from exposure to C. difficile until their bowel
      flora recovers. While several biotherapeutic approaches to the treatment and
      prevention of C. difficile infection have been described, few controlled data are
      available. Preliminary studies with anti-C. difficile bovine immunoglobulin
      concentrates for treatment and prevention have produced promising results.
      Vaccination to prevent C. difficile infection, particularly in high-risk elderly
      patients managed within institutions where C. difficile is endemic, is a
      worthwhile therapeutic goal.

PMID- 9630374
TI  - The epidemiology and typing of Clostridium difficile.
AB  - Clostridium difficile is normally a harmless environmental bacterium but, under
      certain circumstances, it can cause hospital outbreaks of disease. To understand
      the disease epidemiology, outbreaks have been investigated by many different
      methods. The phenotypic and genotypic approaches to typing are reviewed here and
      the epidemiology of C. difficile-associated disease is elucidated in light of
      recent information.

PMID- 9630375
TI  - Infection control and prevention of Clostridium difficile infection.
AB  - Clostridium difficile has become a major problem as a nosocomial pathogen that is
      associated with the use of antibiotics. In the prevention and control of C.
      difficile disease it is important that programmes are directed at primary and
      secondary prevention. The three main elements of prevention are: (i) restricted
      use of antibiotics; (ii) strict enteric precautions when looking after patients
      with diarrhoea; and (iii) meticulous cleaning of clinical areas. Although poor
      handwashing is known to play a key role in the spread of infection, there is
      evidence that compliance with handwashing protocols is low in many hospitals.
      Infection control teams need to continue to develop creative education programmes
      to improve compliance with simple infection control procedures. Consideration
      needs to be given to ensure that patients have access to handwashing and are well
      informed about infection prevention. Further work needs to be carried out to
      establish the efficacy of disinfectants in the environment and the identification
      of a user-friendly, effective sporicide. The importance of both thorough cleaning
      with detergents to reduce the number of spores in the environment, and clean
      equipment for each patient should continue to be emphasized.

PMID- 9630376
TI  - Clostridium difficile infections of the gut: the unanswered questions.

PMID- 9630377
TI  - Clostridium difficile infection: appendix.

PMID- 9630378
TI  - Other men's (and women's) flowers.

PMID- 9630380
TI  - Swedish obese subjects (SOS): an obesity intervention study with a nutritional
      perspective.
AB  - OBJECTIVES: Swedish Obese Subjects (SOS) is a multidisciplinary project involving
      aspects of obesity ranging from description of the severely obese state to
      effects of surgical intervention on long-term mortality and morbidity. Dietary
      studies, which represent an integral part of SOS research activities, are the
      focus of this review. SUBJECTS AND METHODS: Due to the large number of obese
      subjects included in the SOS data bases ( > 5000), an early priority of the
      project was to develop a dietary assessment method which: (i) described usual
      intake patterns; (ii) could be self-administered by subjects and rapidly
      processed; and (iii) was equally valid in obese and non-obese individuals.
      RESULTS: The SOS method has met these requirements and is now being completed by
      all subjects at baseline and during the intervention, and by a non-obese
      reference population. A number of dietary features distinguishing obese subjects
      have emerged, including: elevated intakes of energy and energy-percent fat; low
      consumption of alcohol, fruits and vegetables; high dietary disinhibition;
      frequent consumption of light meals and snacks; and night eating. In the surgical
      intervention group, a relatively high consumption of sweet foods was associated
      with better weight loss and maintenance. CONCLUSIONS: The SOS method appears to
      be less susceptible to obesity-related under-reporting than traditional dietary
      methods, and if the distribution of foods and nutrients can be assumed to be as
      unbiased as the energy intakes, this method should make it possible to capture
      associations between diet and obesity-related diseases in the future.

PMID- 9630379
TI  - Monounsaturated oils do not all have the same effect on plasma cholesterol.
AB  - Evidence assembled here indicates that when olive oil forms a major part of
      dietary fat in controlled human experiments, total and LDL-cholesterols are
      somewhat higher than when the same amount of fat is one of the modern
      predominantly monounsaturated oils: low erucic rapeseed or high oleic sunflower
      oil. Oils rich in monounsaturated fatty acids thus do not all have the same
      effect on plasma cholesterol. This phenomenon is explicable by consideration of
      the content of other fatty acids and the non-saponifiable fractions of the
      different monounsaturated oils. It helps to explain the discrepancy that has
      existed between the classic experiments (using olive oil), which found
      monounsaturated oils 'neutral', and some of the more recent experiments which
      found them more cholesterol-lowering than carbohydrates. Four published meta
      analyses are reviewed. The three which included most of the published experiments
      show that monounsaturated fatty acids (MUFA) have less plasma cholesterol
      lowering effect than polyunsaturated fatty acids.

PMID- 9630381
TI  - Obesity and nutrition in children. The Belgian Luxembourg Child Study IV.
AB  - OBJECTIVE: To analyse the association between nutritional and familial factors
      and obesity in boys and girls. DESIGN: Randomized, cross-sectional population
      study. SETTING: Province de Luxembourg, Belgium. SUBJECTS: One thousand and
      twenty-eight boys and girls in age strata 6-8, 8-10 and 10-12 y, comprising 70.3%
      of primary cohort. METHODS: Examinations included anthropometric measurements and
      questionnaires covering familial, socioeconomic and psychosocial factors. A three
      day dietary record was obtained in 955 children. This was analysed in relation to
      the anthropometric data. RESULTS: In comparison with similar studies from other
      regions and recommended allowances, the intakes of total energy, fat,
      particularly saturated fat and cholesterol, were high, while consumption of
      carbohydrate and fiber was low, as well as the polyunsaturated/saturated ratio of
      fat. Total energy intake showed no or weakly significant correlations with
      anthropometric factors. However, total fat (P=0.045) and saturated fat (P=0.0005)
      intake showed consistent positive correlations with body mass index (BMI, kg/m2)
      and skinfold thickness, with corresponding negative relationships to carbohydrate
      intake (P=0.034) in boys. Such relationships were also found when calculated as
      energy density. These associations were not statistically significant in girls.
      The high fat, low carbohydrate pattern of the nutritional status seemed to be
      more pronounced in families where the father had a low level of education
      (lipids, boys, P=0.0007), and where both parents were obese (saturated fat, boys,
      P=0.023), suggesting involvement of socioeconomic and familial factors.
      CONCLUSION: The lack of correlation between factors indicating obesity and total
      energy intake suggests that the positive energy balance causing obesity is due
      mainly to a low energy output. However, since energy intake measurements are
      imprecise, overeating can not be excluded, particularly since elevated
      consumption of food with high contents of fat, found in these children seems to
      be poorly regulated.

PMID- 9630382
TI  - Sustained improvement in blood lipids, coagulation, and fibrinolysis after major
      weight loss in obese subjects.
AB  - OBJECTIVE: To study whether major weight loss causes sustained improvement in
      blood lipids and haemostatic profile in obese subjects, and to compare the
      influence of two different slimming and maintenance regimens. DESIGN: Two
      stranded randomized intervention study. SETTING: University Department. SUBJECTS:
      Thirty-six out of 43 obese patients recruited from out-patient waiting list
      completed the study. INTERVENTIONS: Weight loss was achieved by very low energy
      formula diet (2 MJ/d for 8 weeks, n=18), or low-energy conventional diet (5 MJ/d
      for 17 weeks, n=18), both combined with anorectic compound. Participants were re
      randomized to consume low fat diet ad libitum (n=16), or energy-restricted diet
      (n=20) for weight maintenance during 24 weeks. MAIN OUTCOME MEASURES: Plasma
      lipids, fibrinogen, factor VII coagulant activity (FVIIc), and plasminogen
      activator inhibitor type 1 (PAI-1) antigen. RESULTS: Weight loss averaged 13.6 kg
      (95% CI: 12.3-14.9 kg). After 24 weeks' weight maintenance, plasma total
      cholesterol was 9% lower, high density lipoprotein cholesterol 5% higher,
      triglycerides 30% lower, FVIIc 12% lower, fibrinogen 6% lower, and PAI-1 antigen
      34% lower than at baseline (all changes highly significant). There were no
      significant differences between slimming or maintenance regimens. CONCLUSIONS:
      Major weight loss is associated with sustained and marked improvements in blood
      lipids and hemostatic profile, irrespective of the tested slimming and
      maintenance regimens.

PMID- 9630383
TI  - Plant sterol-enriched margarines and reduction of plasma total- and LDL
      cholesterol concentrations in normocholesterolaemic and mildly
      hypercholesterolaemic subjects.
AB  - OBJECTIVES: To compare effects on plasma total-, LDL-, and HDL-cholesterol
      concentrations of margarines enriched with different vegetable oil sterols or
      sitostanol-ester. DESIGN: A randomized double-blind placebo-controlled balanced
      incomplete Latin square design with five treatments and four periods of 3.5
      weeks. Margarines enriched with sterols from soybean, sheanut or ricebran oil or
      with sitostanol-ester were compared to a non-enriched control margarine. Sterol
      intake was between 1.5-3.3 g/d. Two thirds of the soybean oil sterols were
      esterified to fatty acids. SETTING: Unilever Research Laboratory, Vlaardingen,
      The Netherlands. SUBJECTS: One hundred healthy non-obese normocholesterolaemic
      and mildly hypercholesterolaemic volunteers aged 45+/-12.8 y, with plasma total
      cholesterol levels below 8 mmol/L at entry. MAIN OUTCOME MEASURES: Plasma lipid,
      carotenoid and sterol concentrations, blood clinical chemistry and haematology,
      fatty acid composition of plasma cholesterylesters and food intake. RESULTS:
      Ninety-five volunteers completed the study. None of the margarines induced
      adverse changes in blood clinical chemistry, serum total bile acids or
      haematology. Plasma total- and LDL-cholesterol concentrations were significantly
      reduced by 8-13% (0.37-0.44 mmol/L) compared to control for margarines enriched
      in soybean oil sterol-esters or sitostanol-ester. No effect on HDL-cholesterol
      concentrations occurred. The LDL- to HDL-cholesterol ratio was reduced by 0.37
      and 0.33 units for these margarines, respectively. Effects on blood lipids did
      not differ between normocholesterolaemic and mildly hypercholesterolaemic
      subjects. Plasma sitosterol and campesterol levels were significantly higher for
      the soybean oil sterol margarine and significantly lower for the sitostanol-ester
      margarine compared to control. Dietary intake was very similar across treatments.
      The fatty acid composition of plasma cholesterylesters confirmed the good
      compliance to the treatment. All sterol enriched margarines reduced lipid
      standardized plasma alpha- plus beta-carotene levels. Plasma lycopene levels were
      also reduced but this effect was not significant for all products. CONCLUSIONS: A
      margarine with sterol-esters from soybean oil, mainly esters from sitosterol,
      campesterol and stigmasterol, is as effective as a margarine with sitostanol
      ester in lowering blood total- and LDL-cholesterol levels without affecting HDL
      cholesterol concentrations. Incorporation in edible fat containing products of
      such substances may substantially reduce the risk of cardiovascular disease in
      the population.

PMID- 9630384
TI  - Humoral and cell-mediated immunity in malnourished children in Ghana.
AB  - OBJECTIVE: To examine the relationship between immunological variables and the
      different types and severity of malnutrition in Ghanaian children. DESIGN: Case
      control study. SETTING: The study was done at Princess Marie Louise Hospital,
      Accra, Ghana. SUBJECTS: One hundred and seventy children, aged 8-36 months, were
      recruited at the clinical ward and public health service section of the hospital:
      61 normal children, 49 moderately malnourished (underweight) children and 60
      severely malnourished children (19 kwashiorkor, 30 marasmus, and 11 marasmic
      kwashiorkor children). METHOD: The children underwent clinical observations,
      anthropometric measurements and blood sampling for biochemical analysis to
      evaluate their nutritional and immunological status. Serum immunoglobulins (IgA
      subclasses, IgG subclasses and IgM), complements (C3 and C4) and lymphocyte
      subpopulations (T cells, B cells, CD4+, CD8+, NK cells and HLADR) were determined
      for the assessment of humoral and cell-mediated immunity. RESULTS: Serum levels
      of IgA1, IgA2 and C4 tended to be higher in severely malnourished children than
      in normal children, while serum level of C3 and the proportion of B cells were
      significantly lower in the severely malnourished children than in the normal
      children (P < 0.05). There were no notable differences in most immunological
      parameters among the three severely malnourished groups. No differences were
      observed in the immunological parameters except for the proportion of B cells
      between normal and moderately malnourished children. Factor analysis revealed
      that C3 levels were positively correlated with a factor which was strongly
      associated with weight-for-height z-score and biochemical indicators for
      evaluating protein nutrition. In addition, IgA2, IgG1 and IgM levels were
      positively correlated with a factor which was associated with C-reactive protein.
      CONCLUSION: Several immunological variables responded positively or negatively
      with the different levels of severity of malnutrition, but most variables did not
      on the different types of malnutrition. The changes of C3 level were more
      associated with the severity of malnutrition.

PMID- 9630385
TI  - Iodine status, thyroid function and pregnancy: study of Swedish and Sudanese
      women.
AB  - OBJECTIVE: To examine and compare the effects of pregnancy on the thyroid hormone
      homeostasis in two different populations with variable iodine supply. DESIGN: A
      longitudinal prospective cohort study throughout pregnancy involving Swedish and
      Sudanese pregnant women. SETTING: The subjects were enrolled consecutively during
      their antenatal follow-up at health centres at Nyby in Uppsala, Sweden and
      Omdurman in Sudan. SUBJECTS: Fifty-one apparently healthy women from Uppsala,
      Sweden and twenty-eight pregnant women from Omdurman, Sudan were recruited during
      pregnancy. The mean age and weight of the Swedish women at the beginning of
      pregnancy were 29.9+/-5.4 y and 66.3+/-12.9 kg respectively. The corresponding
      figures for the Sudanese women were 28.0+/-4.9 y and 64.8+/-9.4 kg respectively.
      METHODS: Blood samples were drawn on four occasions from the Swedish group at 11
      13, 24, 32, and 38 weeks of pregnancy, and on three occasions from the Sudanese
      group at 10-12, 20-24, and 36-39 weeks. Twenty-four hour urine samples were
      collected from the same subjects and on the same occasions as blood sampling. The
      urine samples were kept in a refrigerator until the volumes were measured, after
      which 20 mL aliquots were taken and kept frozen until analysed. MAIN OUTCOME
      MEASURES: Twenty-four hour urinary iodine output, TSH, FT4 and T3. RESULTS: The
      24 h urinary iodine output at the different times during gestation were higher
      among the Swedish women, with mean values (95% confidence interval) of 1.40 (1.19
      1.61), 1.33 (1.14-1.51), 1.45 (1.06-1.84) and 1.14 (0.88-1.39) micromol/d, than
      among the Sudanese cohort, with corresponding values of 0.49 (0.27-0.72), 0.29
      (0.19-0.39), 0.56 (0.25-0.88) micromol/d. No significant changes in daily urinary
      iodine loss were observed in the two groups with progression of pregnancy.
      However, in the Swedish women the mean free T4 concentration fell from 11.81
      pmol/l at the beginning of pregnancy to 8.82 pmol/l and the mean TSH rose from
      1.11-1.95 mU/I between the beginning and end of pregnancy. Such changes were not
      detected among the Sudanese women, who had significantly lower mean TSH values
      than the Swedish women in weeks 36-39 of pregnancy (P < 0.02), and significantly
      higher FT4 values than the Swedish women both in weeks 20-24 and in weeks 36-39
      (P < 0.005 and P < 0.001) respectively. CONCLUSIONS: The study suggests that
      determination of urinary iodine alone gives inadequate information about the
      capacity of an individual to utilize an available iodine supply and it also shows
      the existence of different patterns of thyroid response during pregnancy. The
      history of iodine availability prior to and during pregnancy seems to be an
      important determinant of the mechanism of thyroid gland response to ensure the
      extra iodine needed by the growing fetus.

PMID- 9630386
TI  - Bioavailability of catechins from tea: the effect of milk.
AB  - OBJECTIVES: To assess the blood concentration of catechins following green or
      black tea ingestion and the effect of addition of milk to black tea. DESIGN:
      Twelve volunteers received a single dose of green tea, black tea and black tea
      with milk in a randomized cross-over design with one-week intervals. Blood
      samples were drawn before and up to eight hours after tea consumption. SETTING:
      The study was performed at the Unilever Research Vlaardingen in The Netherlands.
      SUBJECTS: Twelve healthy adult volunteers (7 females, 5 males) participated in
      the study. They were recruited among employees of Unilever Research Vlaardingen.
      INTERVENTIONS: Green tea, black tea and black tea with semi-skimmed milk (3 g tea
      solids each). RESULTS: Consumption of green tea (0.9 g total catechins) or black
      tea (0.3 g total catechins) resulted in a rapid increase of catechin levels in
      blood with an average maximum change from baseline (CVM) of 0.46 micromol/l (13%)
      after ingestion of green tea and 0.10 micromol/l (13%) in case of black tea.
      These maximum changes were reached after (mean (s.e.m.)) t=2.3 h (0.2) and t=2.2
      h (0.2) for green and black tea respectively. Blood levels rapidly declined with
      an elimination rate (mean (CVM)) of t1/2=4.8 h (5%) for green tea and t1/2=6.9 h
      (8%) for black tea. Addition of milk to black tea (100 ml in 600 ml) did not
      significantly affect the blood catechin levels (areas under the curves (mean
      (CVM) of 0.53 h. micromol/l (11%) vs 0.60 h. micromol/l (9%) for black tea and
      black tea with milk respectively. CONCLUSION: Catechins from green tea and black
      tea are rapidly absorbed and milk does not impair the bioavailability of tea
      catechins.

PMID- 9630387
TI  - Respiratory quotient changes in full term newborn infants within 30 hours from
      birth before start of milk feeding.
AB  - OBJECTIVE: To evaluate substrate utilization in full-term newborn infants, fed
      every 3-4 h with glucose 10% solution, within 30 h from birth. DESIGN: Random.
      SETTING: Full term newborn infants at the Paediatric Division City Major
      Hospital, Chair of Paediatrics, Verona University. SUBJECTS: Forty-six newborn
      infants, 24 females and 22 males of 39+/-2 weeks gestational age. METHODS: Oxygen
      consumption (VO2) and CO2 production (VCO2) were measured. Permitting the
      computation of the respiratory quotient (RQ), which expresses substrate
      oxidation, at 6 and 30 h from birth. An indirect calorimeter (Deltratrac TMII-MBM
      200-DATEX) was used to measure components of energy-balance. RESULTS: Energy
      expenditure calculated at 6 h was 8.130 (+/-1.5757) kJ/kg/h. At 30 h the value
      changed to 8.858 (+/-1.483) kJ/kg/h. Statistical evaluation (t-student) showed a
      significant (P=0.000) variation in RQ values (6 h: RQ=0.94; 30 h: R=0.88).
      CONCLUSIONS: Respiratory quotient suggests an increase of energy derived from fat
      metabolism at 30 h from birth. Our data confirm that early breast feeding or
      formula milk feeding could represent a physiological approach to nutritional
      regimen of the newborn infant.

PMID- 9630388
TI  - Plasma selenoprotein P levels of healthy males in different selenium status after
      oral supplementation with different forms of selenium.
AB  - OBJECTIVE: To assess changes in selenoprotein P levels in plasma from subjects
      who had received oral supplements of different selenium forms. DESIGN: The same
      study group participated in two similar selenium supplementation trials, Trial I
      in 1981 (Levander et al, 1983) and Trial II in 1987 (Alfthan et al, 1991). During
      Trial II the mean baseline intake of selenium in Finland was higher compared to
      that during Trial I (100 and 40 microg/d, respectively), due to a nationwide
      supplementation of fertilisers which started in 1985. SUBJECTS: Fifty healthy
      Finnish men, 36-60 y old. INTERVENTION: The study group received daily placebo or
      oral supplements consisting of 200 microg selenium as selenium-enriched yeast,
      sodium selenate or selenium-enriched wheat (Trial I) or selenium-enriched yeast,
      sodium selenate or sodium selenite (Trial II). The duration of supplementation
      periods was 11 (Trial I) and 16 (Trial II) weeks. RESULTS: In Trial I the mean
      plasma selenoprotein P values in all the supplemented groups increased
      significantly, approaching a plateau at 2 weeks and reaching maxima at 4 weeks
      (mean increase 34%, P < 0.05). In Trial II the mean selenoprotein P levels of the
      supplemented groups were not significantly different from each other or from the
      placebo group at the start or at any time point of the supplementation period.
      CONCLUSIONS: At a low selenium status the selenoprotein P levels increased in a
      similar fashion after supplementation with different forms of selenium, but at a
      high selenium status no significant effects of supplementation with the same
      amount of selenium were observed. No differences in selenoprotein P levels were
      observed for inorganic and organic selenium supplements.

PMID- 9630389
TI  - Delayed gastric emptying rate may explain improved glycaemia in healthy subjects
      to a starchy meal with added vinegar.
AB  - OBJECTIVES: The aim of the study was to evaluate the possible influence of acetic
      acid (administered as vinegar) on the postprandial glucose and insulin responses,
      and the potential involvement of a modified gastric emptying rate was studied by
      use of paracetamol as a marker. DESIGN: The white bread reference meal as well as
      the corresponding meal supplemented with vinegar had the same content of starch,
      protein and fat. The meals were served in the morning after an over-night fast
      and in random order. Capillary blood samples for analysis of glucose, insulin and
      paracetamol were collected postprandially. SETTING: The study was performed at
      the Department of Applied Nutrition and Food Chemistry, Lund University, Sweden.
      SUBJECTS: Ten healthy volunteers, seven women and three men, aged 22-51 y, with
      normal body mass indices were recruited. RESULTS: The presence of acetic acid,
      given as vinegar, significantly reduced the postprandial glucose (GI=64) and
      insulin responses (II=65) to a starchy meal. As judged from lowered paracetamol
      levels after the test meal with vinegar, the mechanism is probably a delayed
      gastric emptying rate. CONCLUSIONS: Fermented foods or food products with added
      organic acids should preferably be included in the diet in order to reduce
      glycaemia and insulin demand.

PMID- 9630390
TI  - Low levels of urinary iodine excretion in schoolchildren of rural areas in Cuba.
AB  - OBJECTIVE: We set up a baseline data on urinary iodine excretion from a
      nationwide representative sample of rural schoolchildren before instituting
      iodine supplementation. DESIGN: Stratified multistage cluster sampling in three
      different strata: lowlands, foothills and mountainous areas. Early morning urine
      samples were collected for evaluation of iodine status. SETTING: Field study in
      25 municipalities in 11 out of 14 provinces. The study was carried out from
      October to December 1995. SUBJECTS: Three thousand and twenty-seven
      schoolchildren of either sex, 6 to < 12 y from 87 primary schools. RESULTS: The
      median urinary iodine excretion was 95 microg/L for the whole sample. The
      situation in a few foothills and all mountainous areas showed a moderate to
      severe deficiency. In the mountainous stratum, the median urinary iodine
      excretion values was less than 20 microg/L. CONCLUSIONS: Cuba has a mild iodine
      deficiency public health problem with respect to WHO criteria, which in the
      mountainous areas is severe. The Government of Cuba has started a national Plan
      of Action and funds are being mobilized to introduce nationwide iodized salt.

PMID- 9630391
TI  - Effect of a mild infection on serum ferritin concentration--clinical and
      epidemiological implications.
AB  - OBJECTIVES: To study the distribution of serum ferritin concentration in
      adolescent boys and girls with and without a preceding mild infection. DESIGN:
      The prevalence of iron deficiency was studied in two representative samples. The
      first sample from 1990 comprised 207 boys and 220 girls. The second sample from
      1994 included 620 boys and 624 girls. In total 1675 adolescents, 15-16 y old, 827
      boys and 844 girls were studied. RESULTS: A significant shift of serum ferritin
      concentration towards higher values was observed in those who reported an upper
      respiratory infection with fever during the preceding month (P<0.001).
      Significant differences were found between serum ferritin values in healthy, not
      infected adolescents and serum ferritin values in those with ongoing infection,
      both in boys and girls in the two materials (P < 0.01), and in those with a mild
      infection during the preceding three weeks. CONCLUSIONS: The prevalence of recent
      infection should be included as information when trying to assess the prevalence
      of iron deficiency on the basis of serum ferritin measurements and when examining
      relationships between iron status and composition of the diet. The findings imply
      that differences in prevalence of iron deficiency between different studies might
      partly be explained by differences in prevalence of simple respiratory
      infections. The diagnostic sensitivity of the serum ferritin assay for iron
      deficiency, using conventional reference limits, decreases for subjects with
      recent such infections; similarly, there will be a decrease in the diagnostic
      specificity for haemochromatosis.

PMID- 9630392
TI  - Comparison of self-report of reduced fat and salt foods with sales and supply
      data.
AB  - OBJECTIVE: Examine the validity of self-reported use of reduced fat and reduced
      salt foods. DESIGN: Compare data collected in a food frequency questionnaire with
      supermarket sales data and food supply data. SETTING: Rural Australia. SUBJECTS:
      Four hundred and fifty-three respondents from an original sample of 1616 randomly
      selected residents. INTERVENTIONS: Community health campaign to reduce
      cardiovascular disease. RESULTS: Reported use of reduced fat and reduced salt
      foods was greater than store sales and milk deliveries of these products.
      CONCLUSIONS: External data did not support the validity of self-reported use of
      these products.

PMID- 9630393
TI  - Kainate glutamate receptors (GluR5-7) in the rat arcuate nucleus: relationship to
      tanycytes, astrocytes, neurons and gonadal steroid receptors.
AB  - Glutamate action, through its ionotropic, kainate receptors, has been implicated
      in gonadal steroid-dependent mechanisms of the arcuate nucleus. The objective of
      the present study was to determine the expression of kainate glutamate receptors
      in neural and glial elements of this area and their potential relationship to
      gonadal steroid receptors. Single and double label, light and electron
      microscopic immunocytochemistry for kainate glutamate receptors and estrogen or
      androgen receptors revealed the existence of glutamate (GluR) 5-7 kainate
      receptors in tanycytes, astrocytes and neurons of the arcuate nucleus. In the
      arcuate nucleus, subsets of GluR5-7-containing neurons were also immunopositive
      for estrogen (20%) and/or androgen receptors (23%). Glial elements, however,
      lacked labeling for gonadal steroid receptors. The coexistence of gonadal and
      kainate receptors in the same perikarya of arcuate nucleus cell populations
      suggests hormone regulation of excitatory neurotransmission through ionotropic
      glutamate receptors in these regions. It is also indicated that a kainate
      receptor-mediated glutamate action may participate in neuro-glial interaction in
      the arcuate nucleus that, in turn, may underlie the morphological synaptic
      plasticity induced by gonadal steroids.

PMID- 9630394
TI  - Comparison of afferent and efferent competence of transplanted GnRH cells in the
      brains of hypogonadal female mice.
AB  - A deletion in the gene encoding gonadotropin-releasing hormone (GnRH) induces
      hypogonadism in mice caused by the deficiency of GnRH. Activation of the
      reproductive axis can be achieved in these hypogonadal (hpg) mice by third
      cerebro-ventricular transplantation of preoptic area (POA) containing GnRH
      neurons, obtained from normal fetal mice. The present study was carried out in
      female hpg mice with POA grafts (hpg/POA) to investigate anatomical integration
      of the GnRH cells required for the functional activation of the reproductive
      system. Ovarian development was present only in mice in which the graft tissue
      was located close to the median eminence (ME). The total lack of ovarian
      development in individuals with grafts containing GnRH cells located elsewhere in
      the brain suggests that the mere presence of GnRH cells does not guarantee
      ovarian development, but that the location of the graft may be important.
      Activation of the grafted GnRH cells following mating, as evidenced by the
      induction of Fos immunoreactivity, was observed in hpg/POA mice in which there
      was no ovarian development or detectable GnRH immunoreactive fiber innervation of
      the ME. Although ovarian development was evident in individuals with grafts
      located close to the ME, release of luteinizing hormone (LH) in response to
      mating was apparent in only some of these mice. The occurrence of mating and
      pregnancy only in hpg/POA mice with ovarian development and the reflex release of
      LH in response to mating suggests that both the efferent and afferent connections
      of the GnRH system are important for the full functioning of the system.

PMID- 9630395
TI  - Enhanced response of growth hormone to growth hormone-releasing hormone and a
      decreased content of hypothalamic somatostatin in a stress-induced rat model of
      depression.
AB  - This study was designed to evaluate changes in the hypothalamic somatostatin
      growth hormone axis (SRIF-GH axis) in a stress-induced rat model of depression.
      We exposed male Wistar rats to intermittent walking stress for two weeks, and
      then measured their spontaneous running activities for 12 days. We divided the
      rats into the depression-model group and the partial recovery group according to
      their spontaneous running activities after the termination of exposure to stress.
      We examined the secretion of GH from the anterior pituitary by injecting human GH
      releasing hormone (hGHRH) with intracardiac cannulae or by applying hGHRH or SRIF
      to isolated anterior pituitaries using a perifusion system. We also determined
      SRIF content in the stalk-median eminence (SME) and the plasma concentration of
      GH. In the depression-model group, intracardiac administration of hGHRH caused
      the enhanced release of GH into plasma, while application of hGHRH or SRIF to the
      anterior pituitary in vitro had similar effects on GH release in the control and
      partial recovery groups. Furthermore, the SRIF content was decreased in the SME
      and the GH concentration was increased in plasma. The partial recovery group gave
      similar values to the control group. The enhanced response of GH to hGHRH in the
      depression-model group might have been caused by the reduced content of SRIF in
      the SME in view of the unchanged response of GH to the infusion of hGHRH or SRIF
      in the perifusion system.

PMID- 9630396
TI  - Developmental expression and regulation of aromatase- and 5alpha-reductase type I
      mRNA in the male and female mouse hypothalamus.
AB  - Androgen metabolites synthesized by neural aromatase and 5alpha-reductase are
      implicated in many aspects of mammalian brain development and, in particular, in
      the masculinization of distinct central nervous system structures and brain
      functions. The present study was designed to determine (1) the developmental
      profile of aromatase- and 5alpha-reductase type I mRNA expression in the mouse
      hypothalamus and (2) to relate ontogenetic sex differences in aromatase activity
      which have been described in the past to sex-specific aromatase gene expression.
      In addition, we analysed the effect of androgens on the perinatal regulation of
      hypothalamic aromatase and 5alpha-reductase type I mRNA expression. By applying
      semiquantitative reverse transcription-polymerase chain reaction analysis, we
      found hypothalamic aromatase mRNA expression to be developmentally regulated and
      to display sex differences at birth and on postnatal day 15 with higher mRNA
      levels in males. Newborn males and females, which were treated in utero with the
      androgen receptor antagonist cyproterone actetate, exhibited significantly
      reduced aromatase mRNA levels compared with untreated controls. In contrast to
      aromatase, expression levels of hypothalamic 5alpha-reductase mRNA did not reveal
      a clear-cut developmental profile or sex differences, and no regulatory role for
      androgens in controlling 5alpha-reductase mRNA expression was found. In
      conclusion, these results demonstrate perinatal sex differences in hypothalamic
      aromatase- but not 5alpha-reductase gene expression and suggest that sex
      differences in perinatal aromatase activity are reflected by corresponding
      differences in mRNA levels. Androgens are found to control brain estrogen
      formation pretranslationally at the level of aromatase gene expression. Our
      findings imply that sex differences in androgen availability and responsiveness
      are important regulatory factors for aromatase expression in the developing male
      hypothalamus.

PMID- 9630397
TI  - Sensitivity of hypothalamic paraventricular nucleus to C- and N-terminal
      angiotensin fragments: vasopressin release and drinking.
AB  - We studied the effect of angiotensin (ANG) peptides and their C- and N-terminal
      fragments, microinjected bilaterally into the hypothalamic paraventricular
      nucleus (PVN) of male Wistar rats, on arginine vasopressin (AVP) release into the
      blood and drinking. ANG II (1-8) and the C-terminal ANG III (2-8) at 0.1-100
      pmol/200 nl induced a dose-dependent increase in AVP release with a maximum of
      26.45+/-6.0 and 31.86+/-7.0 pg/ml, respectively, vs 1.6+/-2.0 pg/ml in vehicle
      treated controls (P<0.001). The highest dose of ANG II and ANG III also induced
      drinking responses of 4.3+/-0.78 and 2.91+/-0.54 ml water/15 min, respectively.
      Bilateral pretreatment of the PVN with the AT1 receptor antagonist losartan (4
      nmol/200 nl) inhibited ANG II- and ANG III-induced AVP release and drinking.
      Different doses of the C-terminal ANG IV (3-8), ANG (4-8) or ANG (5-8) peptides
      did not induce AVP release or drinking. The N-terminal ANG (1-7) peptide induced
      a dose-dependent increase in AVP release (maximum 8.5+/-3.5 pg/ml after 100 pmol)
      but the effect was much less potent than that induced by the same dose of ANG II
      or ANG III. ANG (1-7) failed to induce a drinking response. Pretreatment of the
      PVN with losartan or the AT2 receptor antagonist, PD 123177 (4 nmol/200 nl),
      inhibited the 100 pmol ANG (1-7)-induced AVP release. The N-terminal ANG (1-4)
      peptide did not affect AVP release or drinking at any dose tested. Our data
      demonstrate that the C-terminal ANG II (1-8) and ANG III (2-8), but not shorter
      fragments, can induce AVP release and drinking response via AT1 receptors in the
      PVN. The N-terminal ANG (1-7) was less potent in stimulating AVP release than ANG
      II or ANG III and had no influence on drinking. Thus, the presence of both
      arginine2 and phenylalanine8 in the angiotensin peptide sequence appears to be
      important to elicit AVP release and drinking from the PVN in vivo.

PMID- 9630398
TI  - Cloning, expression, pharmacology and tissue distribution of the mouse
      somatostatin receptor subtype 5.
AB  - The gene encoding the mouse somatostatin receptor subtype 5 has been isolated
      from a genomic library and the mRNA start point mapped to position -95 relative
      to the translational start codon. The promoter region is devoid of TATA and CAAT
      boxes but contains putative binding sites for AP-1, AP-2 and SP1 and response
      elements for glucocorticoids (GRE) and phorbol esters (TRE). The encoded receptor
      protein with a predicted molecular weight of 42.5 kDa is comprised of 385 amino
      acids and thus contains 22 and 21 amino acids more than rat and human
      counterparts. The extra amino acids are caused by another translational
      initiation codon located further upstream. In the region of overlap the mouse
      somatostatin receptor subtype 5 displays 96.7% sequence identity to the rat and
      81.7% to the human homologue. Application of somatostatin-14 and -28 to human
      embryonic kidney cells expressing the recombinant receptor resulted in the
      inhibition of forskolin-stimulated adenylyl cyclase with comparable EC50 values.
      Consistent with the observed sequence relationship, the mouse somatostatin
      receptor subtype 5 displays a pharmacological profile that resembles the rat
      homologue more closely than the human counterpart. mRNA for the mouse
      somatostatin type 5 receptor has been detected in pituitary, kidney, spleen and
      ovary and, to a lesser extent, in brain, stomach, intestine and thymus but was
      not observed in heart, pancreas and liver.

PMID- 9630399
TI  - Finasteride blocks the reduction in ictal activity produced by exogenous estrous
      cyclicity.
AB  - The purpose of the present study was to examine seizure activity during reduced
      5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP) production. Ovariectomized
      Long-Evans rats were stereotaxically implanted with bipolar electrodes above the
      perforant pathway; silastic implants filled with estradiol-17-benzoate (EB) and
      progesterone were inserted subcutaneously to mimic diestrus. Estrus was then
      induced in half of these animals by injection of EB (30 microg) and progesterone
      (2.5 mg), 48 and 4 h, respectively, prior to perforant pathway stimulation. Half
      of the estrous and diestrous rats also received a 5alpha-reductase inhibitor,
      finasteride (50 mg/kg), 6 h prior to perforant pathway stimulation. The estrous
      condition was associated with reduced number and duration of partial seizures,
      improved performance on a Morris water maze recovery of function test, reduced
      neuronal loss in the hilar region of the hippocampus, and elevated central and
      plasma 3alpha,5alpha-THP, compared to estrus+finasteride, diestrus+vehicle and
      diestrus+finasteride conditions, which did not differ from each another. These
      data suggest antiseizure effects of estrus may be caused, in part, by the action
      of 3alpha,5alpha-THP and that the precipitous decline in 3alpha,5alpha-THP may
      restore seizure threshold to control levels.

PMID- 9630400
TI  - Modification of nitric oxide synthase activity and neuronal response in rat
      striatum by melatonin and kynurenine derivatives.
AB  - Tryptophan is mainly metabolized in the brain through methoxyindole and
      kynurenine pathways. The methoxyindole pathway produces (among other compounds)
      melatonin, which displays inhibitory effects on human and animal central nervous
      systems, including a significant attenuation of excitatory, glutamate-mediated
      responses. The kynurenine pathway produces kynurenines that interact with brain
      glutamate-mediated responses. Nitric oxide (NO) increases glutamate release, and
      melatonin and kynurenines may act via modification of NO synthesis. In the
      present study, the effects of melatonin and four synthetic kynurenines were
      studied on the activity of rat striatal nitric oxide synthase (NOS) and on the
      response of rat striatal neurons to sensorimotor cortex (SMCx) stimulation, a
      glutamate-mediated response. Melatonin inhibited both NOS activity and the
      striatal glutamate response, and these effects were dose-related. Compound A (2
      acetamide-4-(3-methoxyphenyl)-4-oxobutyric acid) did not inhibit NOS activity but
      inhibited the striatal response similarly to melatonin. Compound B (2-acetamide-4
      (2-amino-5-methoxyphenyl)-4-oxobutyric acid) was more potent than melatonin in
      inhibiting both NOS activity and the striatal response. Compound C (2-butyramide
      4-(3-methoxyphenyl)-4-oxobutyric acid) did not change NOS activity, but increased
      the striatal response. Compound D (2-butyramide-4-(2-amino-5-methoxyphenyl)-4
      oxobutyric acid) showed potent inhibitory effects on both NOS activity and
      striatal glutamate-mediated response. A structure-related effect of the
      kynurenine derivatives was observed, and those with an amino group in position 2
      of the benzenic ring had more potent effects than melatonin itself in inhibiting
      striatal NOS activity and the response of striatal neurons to SMCx.

PMID- 9630401
TI  - Regulation of melatonin receptors in the pars tuberalis of Syrian hamsters
      transferred from long to short photoperiod: implication of melatonin and
      testosterone.
AB  - The exposure of long day seasonal breeders to a short photoperiod (SP) induces
      both sexual quiescence and a decrease in pars tuberalis (PT) melatonin receptor
      density. Therefore, we studied the respective roles of melatonin and testosterone
      on the regulation of PT melatonin receptors in Syrian hamsters transferred from
      long photoperiod (LP) to SP. Compared with intact sexually active animals in LP,
      the density of melatonin receptors was not affected by the absence of melatonin
      after removal of the pineal gland from animals kept in either SP or LP. In
      contrast, the presence of a long melatonin peak in the blood which induces
      gonadal atrophy induced a significant decrease in binding capacity. The SP
      induced decrease in PT melatonin receptor density was also observed in castrated
      animals showing that it was directly regulated by melatonin, independently of
      circulating testosterone concentrations. However, the absence of testosterone
      induced an increased binding in LP, while increasing blood testosterone
      concentration after implantation of one testosterone-filled silastic tube
      resulted in a decrease in binding both in LP-and in SP-animals. These results
      indicate that testosterone induces a photoperiod-independent decrease in PT
      melatonin receptor density. In summary, these results show that both melatonin
      and testosterone have negative regulatory effects on the density of PT melatonin
      receptors.

PMID- 9630403
TI  - Use of antibiotic prophylaxis in clean non-implant wounds.

PMID- 9630402
TI  - Oxytocin release from the neurohypophysis after the taste stimuli previously
      paired with intravenous cholecystokinin in anaesthetized rats.
AB  - Intravenously administered cholecystokinin octapeptide (CCK) induces oxytocin
      release from the neurohypophysis in anaesthetised rats. Memory of conditioned
      taste aversion can be acquired under anaesthesia. The present experiments aimed
      at investigating whether taste stimuli previously paired with i.v. CCK evoke
      oxytocin release from the neurohypophysis in urethane-anaesthetised male rats.
      Sucrose solution (0.75-2.0 M) paired with i.v. CCK or the vehicle was applied to
      the tongue. After 3 h, sucrose solution was applied again. The second sucrose
      slightly increased plasma oxytocin concentration in rats that had received the
      first sucrose solution paired with the vehicle. Plasma oxytocin concentration
      after the second sucrose application, however, was significantly higher in CCK
      injected than in vehicle-injected rats. In rats that received CCK 1 h before the
      first sucrose application, a second sucrose application did not produce the
      oxytocin response. The magnitude of the oxytocin response to the second sucrose
      solution was increased in a manner related to CCK doses. In separate experiments,
      NaCl solution (0.75 M) paired with CCK or the vehicle was applied to the tongue.
      The second NaCl solution applied 3 h after the first one facilitated oxytocin
      release both in the rats that had received CCK or the vehicle. The increase in
      plasma oxytocin, however, was significantly larger in CCK than in vehicle
      injected rats. In rats that had received the first sucrose solution paired with
      CCK, a second sucrose solution evoked a significantly larger increase in plasma
      oxytocin concentrations than a testing NaCl solution did. In rats that had
      received NaCl solution paired with CCK, a testing sucrose solution did not
      significantly change plasma oxytocin concentrations. These data suggest that the
      taste stimulus previously paired with i.v. CCK induces oxytocin release from the
      neurohypophysis in urethane-anaesthetised rats.

PMID- 9630404
TI  - The effects of macrolides on the expression of bacterial virulence mechanisms.
AB  - Macrolides are unique among the various classes of antimicrobial agents because
      of the manner in which they interact with pathogens and the host immune system to
      produce a clinical response. Conventional efficacy explanations require the serum
      or tissue concentration of the macrolide to exceed the MIC of the macrolide to
      account for bacteriostatic activity. However, at concentrations below the MIC,
      there are other effects on the expression of proteinaceous virulence factors
      which could prevent the pathogen from establishing or expanding an infection. The
      purpose of this review is to describe these effects and to provide an in-vivo
      scenario delineating the role of macrolides and leucocytes as they contribute to
      clinical efficacy.

PMID- 9630405
TI  - MEN 10700, a new penem antibiotic: in-vitro activity and its correlation with
      beta-lactamase stability, PBP affinity and diffusion through the bacterial cell
      wall.
AB  - The in-vitro activity of MEN 10700, a novel penem, was compared with that of
      imipenem, ritipenem, ampicillin/sulbactam, cefotaxime, ciprofloxacin and amikacin
      against 1088 strains taken from 21 genera, including Gram-negative, Gram-positive
      and anaerobic bacteria. MIC data showed that MEN 10700 was very active against
      staphylococci and streptococci (MIC90 < or = 0.5 mg/L) and against most members
      of the Enterobacteriaceae (MIC90 < or = 2 mg/L), with reduced activity only
      against Providencia stuartii (MIC90 = 8 mg/L). MEN 10700 was also active against
      anaerobic species such as Clostridium perfringens and Bacteroides fragilis as
      well as Moraxella catarrhalis. It was moderately active against Enterococcus
      faecalis and inactive against Pseudomonas aeruginosa, Stenotrophomonas
      maltophilia, Aeromonas spp. and Acinetobacter spp. Its antibacterial spectrum was
      thus slightly narrower than that of imipenem, but compared favourably with those
      of a third-generation cephalosporin and ritipenem. MEN 10700 was highly stable to
      a number of beta-lactamases and was a poor inducer of class I enzymes. It bound
      penicillin-binding protein 2 with the highest affinity and easily permeated the
      outer membrane of Escherichia coli.

PMID- 9630406
TI  - Epidemiological typing of klebsiellae with extended-spectrum beta-lactamases from
      European intensive care units.
AB  - Extended-spectrum beta-lactamases (ESBLs) are an increasing cause of resistance
      to oxyimino-aminothiazolyl cephalosporins, especially in klebsiellae. In a recent
      survey we detected ESBLs in 220 (23%) of 966 consecutive klebsiellae from 35
      intensive care units (ICUs) in southern and western Europe. The present study
      examined the extent to which this distribution reflected epidemic strain spread,
      as against the distribution of ESBL genes into unrelated strains. All 220 ESBL
      producers were subjected to capsular serotyping and pulsed-field gel DNA
      electrophoresis (PFGE). Beta-Lactamases were typed for strains isolated on three
      or more occasions, with the emphasis on SHV enzymes, as these were commoner than
      TEM variants. Serotyping and PFGE typing defined 85 distinct strains, from 23 of
      the 35 participating centres. Of 14 centres that contributed five or more ESBL
      producers, all sent representatives of more than one strain, and two centres sent
      members of ten or more different strains in contributions of 17-21 ESBL-producing
      isolates. Nevertheless, epidemic strains-defined as those represented by three or
      more isolates-accounted for a majority (61%) of the collection. Fifty-two
      isolates of the same serotype K25 (occasionally acapsular) strain with SHV-4 beta
      lactamase were recovered at two French hospitals and one in Belgium. This strain
      has been found by others in France, and has become particularly widespread.
      Another single strain was found in two separate Portuguese centres, and many
      individual hospitals had one or more epidemic strain(s), as well as a scatter of
      diverse ESBL producers. Major variation in antibiogram and plasmid profile was
      apparent within strains, with some intra-strain variation in beta-lactamase type.
      These data imply a fluid situation, with resistance determinants being gained,
      modified or lost. The endemicity of ESBL producers is disturbing since it limits
      the potential for control by blocking strain spread, while the diversity within
      strains is disturbing because it complicates the design of antibiotic policies
      even during 'single strain' outbreaks.

PMID- 9630407
TI  - Fluconazole susceptibility and strain variation of Candida albicans isolates from
      HIV-infected patients with oropharyngeal candidosis.
AB  - Over a 16 month period we conducted a prospective study in a cohort of 45 HIV
      positive patients to detect the development of resistance to fluconazole and to
      analyse the epidemiology of oropharyngeal candidosis (OPC). Each episode was
      treated with fluconazole 100 mg/day po for 10 days. All yeast isolates were
      tested for their in-vitro susceptibility to fluconazole. Multiple strains of
      Candida albicans simultaneously isolated from a given patient were typed by
      electrophoretic karyotyping. Overall, 106 episodes of OPC were diagnosed among
      the 45 patients: 18/45 patients (40%) had only one episode, 11/45 (24%) had two
      episodes, and the remaining 16/45 (36%) had three or more episodes (range 3-7).
      Cure (complete resolution of signs and symptoms and negative post-treatment
      cultures) and improvement (complete resolution of signs and symptoms but positive
      post-treatment cultures) were observed in 30/106 (28%) and 69/106 (65%) episodes
      of OPC, respectively. Failure (absence of improvement or exacerbation of signs
      and symptoms) was observed in seven episodes (7%) from four patients. In two of
      these four patients a significant and progressive increase in fluconazole MICs
      was observed: from 0.25 to 16 mg/L in one patient, and from < or = 0.125 to 32
      mg/L in the second one. Tests on multiple colonies from individual isolation
      plates showed that it was not unusual to obtain different fluconazole MICs,
      indicating that, in order to avoid misleading results, one should perform in
      vitro susceptibility testing by using a multiple colony inoculum rather than an
      inoculum made from a single colony. A total of 213 strains of C. albicans
      isolated from seven patients who suffered from four or more episodes of OPC
      through the course of the study were typed by electrophoretic karyotyping. Five
      individuals (71%) were infected with yeasts with only one DNA type, while the
      other two patients showed the presence of two or three different DNA types. The
      simultaneous presence of multiple types was found only in one of the seven
      subjects. Our data confirm the efficacy of fluconazole 100 mg/day for the
      treatment of OPC in HIV patients. Isolation of fluconazole-resistant strains of
      C. albicans with this regimen is rare. The vast majority of HIV patients are
      infected with a unique strain of C. albicans throughout each episode of
      infection. A minority of patients, however, can harbour strains of C. albicans
      with variable patterns of fluconazole susceptibility simultaneously.

PMID- 9630409
TI  - Application of X-ray micrography and imaging to study the effect of gentamicin on
      Pseudomonas aeruginosa.
AB  - Aminoglycosides disrupt the outer membrane of Pseudomonas aeruginosa to
      facilitate access to their intracellular target. High-resolution X-ray
      micrography of live specimens is a relatively new technique. We used laser
      (nanosecond) plasma to image live cells of P. aeruginosa ATCC 27853. After
      exposure to 25 mg/L gentamicin for 15 min. we observed perturbation of the cell
      surface, membrane blebbings (370 nm and 273 nm diameter) away from the cell,
      formation of distinct channels (241 nm long) resulting from indentation and
      induction of cell elongation from 3-3.6 microm (control) to 4.6-5.26 microm
      (gentamicin-treated cells). These data illustrate the potential of high
      resolution X-ray micrography for studying effects of drugs on live
      microbiological specimens.

PMID- 9630408
TI  - A randomized controlled trial of acyclovir versus netivudine for treatment of
      herpes zoster. International Zoster Study Group.
AB  - Oral acyclovir has become the standard of care for treatment of acute herpes
      zoster. Netivudine is a novel antiviral with greater in-vitro activity against
      varicella zoster virus. It was compared with acyclovir in a randomized, double
      blind, controlled trial in immunocompetent adults with herpes zoster. Patients
      with rash for less than 72 h were assigned to receive either acyclovir or
      netivudine, then assessed regularly for 6 months. No evidence for a dose response
      with netivudine was found, so intent-to-treat analyses of all 511 enrolled
      patients compared acyclovir with netivudine. The time to complete cessation of
      pain (P = 0.007) and to cessation of moderate to excruciating pain (P = 0.005)
      was accelerated in acyclovir recipients. Rash outcomes and adverse event profiles
      were similar for both treatments. This study has confirmed the efficacy of
      acyclovir in decreasing the duration and severity of pain following herpes
      zoster. Greater in-vitro activity of newer agents may not necessarily provide
      greater benefit in humans.

PMID- 9630410
TI  - Antiadhesive effects of xylitol on otopathogenic bacteria.
AB  - The exposure of either epithelial cells or pneumococci or both to 5% xylitol
      reduced the adherence of pneumococci. Exposure of epithelial cells or bacteria
      alone to xylitol did not reduce the adherence of Haemophilus influenzae, although
      the exposure of both cells and bacteria to xylitol reduced the adherence
      significantly. The adherence of Moraxella catarrhalis remained low irrespective
      of the exposure.

PMID- 9630411
TI  - Susceptibility of Aspergillus strains from culture collections to amphotericin B
      and itraconazole.
AB  - Susceptibility testing of 27 Aspergillus reference strains belonging to five
      species was performed using the microdilution broth method with yeast nitrogen
      broth and RPMI-1640. Similar results were found using the two media. The strains
      of Aspergillus fumigatus (n = 8) and Aspergillus niger (n = 4) had MICs of
      amphotericin B in the range 0.125-0.5 mg/L. In contrast, nine out of 13 strains
      of Aspergillus flavus and Aspergillus nidulans had MICs in the range 2-16 mg/L.
      All strains had MICs of itraconazole in the range 0.03-0.5 mg/L. It is concluded
      that both media can be used for testing. Susceptibility testing to amphotericin B
      is recommended in clinical settings.

PMID- 9630412
TI  - Biofilms and beta-lactam activity.

PMID- 9630413
TI  - Nucleotide sequences of inhibitor-resistant TEM beta-lactamases.

PMID- 9630414
TI  - High frequency of mutations at position 2144 of the 23S rRNA gene in
      clarithromycin-resistant Helicobacter pylori strains isolated in Spain.

PMID- 9630415
TI  - Acinetobacter spp. isolates with reduced susceptibilities to carbapenems in a UK
      burns unit.

PMID- 9630416
TI  - Worldwide emergence of carbapenem-resistant Acinetobacter spp.

PMID- 9630417
TI  - Reduced susceptibility to teicoplanin in a methicillin-resistant strain of
      Staphylococcus aureus.

PMID- 9630418
TI  - Symptomatic treatment of brain tumor patients with sodium selenite, oxygen, and
      other supportive measures.
AB  - Patients (16 women and 16 men) with brain tumors previously treated
      conservatively by surgery, radiation, and/or chemotherapy with typical symptoms
      of increased intracranial pressure were consecutively enrolled to test the
      effects of pharmacological dosages of sodium selenite (selenase) in conjunction
      with other supportive therapies (biological response modifiers, detoxification,
      chemotherapy, immunotherapy, oxygen therapy). The rationale for the use of sodium
      selenite was that the whole-blood selenium levels were subnormal in 70% of the
      patients on admission. Patients also frequently presented abnormal levels of
      other minerals, especially lowered sodium and elevated potassium levels, which
      appears to be characteristic of brain tumor patients. Sodium selenite was
      administered by infusion at dosages of 1000 microg Se in physiological saline/d
      for 4-8 wk. In 76% of the patients, a definite, and in 24% a slight improvement
      of the general condition and a decrease in symptoms, such as nausea, emesis,
      headache, vertigo, unsteady gait, speech disorders, and Jacksonian seizures, were
      observed. In all treated patients, improvements of erythrocyte, hemoglobin, and
      thrombocyte counts were observed. Additional beneficial effects were noted in the
      patients receiving the oxygen therapy. It is concluded that the sodium selenite
      can be employed with oxygen therapy and other supportive measures in the
      management of brain tumor patients.

PMID- 9630419
TI  - Changes in blood chemistry, hematology, and histology caused by a
      selenium/vitamin E deficiency and recovery in chicks.
AB  - Exudative diathesis, a condition caused by a selenium (Se)/vitamin E deficiency,
      was studied in chicks. Trios of chicks that showed clinical signs of exudative
      diathesis were matched for severity. One was injected subcutaneously with 0.5 mL
      distilled water, and the other two received 15 microg of Se in 0.5 mL distilled
      water. A chick fed a diet with supplemental Se also received 0.5 mL distilled
      water. Blood was collected from three chicks 2 d after injection, and from the
      other chick, 6 d after injection. After blood was collected, pectoral muscle and
      bone marrow were collected. Deficient chicks showed varying degrees of necrosis
      in pectoral muscle, whereas recovering chicks had extensive fibrosis in pectoral
      muscle. An analysis of blood showed differences in CO2, glucose, Se, glutathione
      peroxidase, alanine aminotransferase, aspartate aminotransferase, and creatine
      kinase. Heterophils and monocytes were increased in deficient chicks;
      lymphocytes, basophils, and hemoglobin decreased. After 6 d of recovery, all of
      the changes noted above were correcting toward normal. Eosinophils, in contrast,
      were unaffected by a deficiency, but increased in recovering chicks. It is
      hypothesized that cytokines associated with the inflammatory response accentuate
      the clinical signs of exudative diathesis.

PMID- 9630420
TI  - A high accumulation of minerals in human internal jugular vein.
AB  - To elucidate age-related changes of mineral contents in human veins, the relative
      contents (RCs) of elements in the human internal jugular veins, superior and
      inferior venae cavae, and femoral veins from 27 subjects ranging from 40 to 98 yr
      old were analyzed by inductively coupled plasma atomic emission spectrometry. The
      average RCs of calcium in the 27 specimens were the highest in the internal
      jugular vein, followed in descending order by the superior vena cava, femoral
      vein, and inferior vena cava. The RCs of calcium and phosphorus in the internal
      jugular veins started to increase after the age of 50 yr, became the highest in
      subjects in their 60s and thereafter decreased gradually. It is noted that such
      accumulations of minerals, similar to the internal jugular vein, were also found
      in the veins, such as the superior and inferior venae cavae, and femoral vein.
      Accumulation of minerals in the veins is different from that of arteries, which
      increase progressively by aging, but do not decrease.

PMID- 9630421
TI  - Effect of gamma-radiation on some elements in certain organs of albino rats.
AB  - Energy-dispersive X-ray fluorescence (EDXRF) was used to determine the
      concentrations of Ca, Cl, Fe, Ni, P, K, Se, S, and Zn in heart, lung, liver,
      spleen, and kidney of adult albino rats 2 mo after they were subject to a single
      gamma gamma-radiation dose from 60Co at 5 gy. In female rats, K levels were
      significantly higher and the Ca levels significantly lower for the irradiated
      animals when compared to age-matched nonirradiated controls. Significant
      differences between irradiated and nonirradiated tissues were observed for other
      elements, although no sex-related differences could be found. Tissue damage and
      disturbances of biological functions were observed as a result of gamma
      irradiation.

PMID- 9630422
TI  - Longitudinal changes in Ca, Mg, Fe, Cu, and Zn in breast milk of women in Taiwan
      over a lactation period of one year.
AB  - The study of the composition of human milk has attracted worldwide interest,
      since it represents the pattern of nutrients most suitable for the younger
      infant. In the present study, the concentration of Ca, Mg, Fe, Cu, and Zn was
      measured in a total of 211 samples of human milk. The analytical technique of
      inductively coupled plasma atomic emission spectrometry (ICP-AES) was used for
      the analysis. From the results, it indicates that the mean concentration of Zn is
      highest in the colostrum with decreasing concentrations as the lactation
      progressed. The effects of age, parity, and lactation history on the results are
      also analyzed. It shows that the Zn concentration in the colostrum in the older
      mothers (>30 yr) was higher than that of the younger ones (20-30 yr).

PMID- 9630423
TI  - Nuclear all-trans retinoic acid receptors: in vitro effects of selenium.
AB  - The present study was undertaken to investigate the effects of selenite (SeIV)
      and selenate (SeVI) on the all-trans retinoic acid (RA)-nuclear retinoic acid
      receptor (RAR) complex formation in rat liver. We also present the data on the in
      vitro effects of SeIV on the RARalpha and the type I iodothyronine 5'-deiodinase
      gene expression in the GH4C1 rat pituitary tumor cells. SeIV at 1.0 micromol/L
      was found to reduce (p < 0.05) the RA specific binding to RAR in rat liver.
      Dithiothreitol (DTT), a protective agent for sulfhydryl groups, was found to be
      slightly effective in protecting the RAR binding properties when affected by
      SeIV. SeVI at 0.1 micromol/L reduced (p < 0.05) the RA specific binding to RAR in
      liver, as well. Seleno-L-methionine (Se-II) when compared to L-methionine did not
      exert any inhibitory effect on the formation of the RA-RAR complex. SeIV (up to
      2.5 micromol/L) has no inhibitory effect on GH4C1 cell proliferation as well as
      the prolactin secretion. SeIV at 1.0 micromol/L significantly decreases the rate
      of mRNA synthesis and/or degradation of the alpha form of the RAR and causes the
      enhancement of the type I iodothyronine 5'-deiodinase gene expression in GH4C1
      cells. The results based on in vitro experiments suggest that inorganic selenium
      may affect the RA specific binding to their cognate receptor molecules, and it
      may reduce expression of the gene encoding the RARalpha, with the cell vitality
      and the cell growth remaining unchanged.

PMID- 9630424
TI  - Uptake of aluminum and gallium into tissues of the rat: influence of antibody
      against the transferrin receptor.
AB  - Transport of aluminum and gallium from blood into rat tissues following
      continuous i.v. infusion of metals in different chemical forms has been
      investigated. Tissue uptake of aluminum and gallium was similar and highly
      dependent on the chemical species of the metals. Aluminum and gallium accumulated
      in liver and spleen when infused in the chloride form. Raised citrate markedly
      enhanced aluminum and gallium uptake into renal cortex and bone; in contrast with
      gallium-transferrin, citrate increased uptake of 67Ga into renal cortex and bone
      by 8- and 14-fold respectively. Uptake of 67Ga with citrate into renal cortex was
      around 3 times smaller than that of aluminum. The antitransferrin receptor
      antibody OX-26 enhanced 67Ga uptake from gallium citrate into all rat tissues.
      67Ga from purified gallium-transferrin was also taken into all tissues in the
      presence of OX-26, the effect being greatest in renal cortex and bone. No
      influence of antibody on aluminum transport into rat tissues was, however,
      observed when aluminum was infused in the citrate form. Therefore, transport of
      aluminum and gallium into tissues is not similar under all conditions. Transport
      of each metal occurs into all tissues in the presence of antitransferrin receptor
      antibody. The potential for such transport is much greater in the case of
      gallium. Transport of aluminum and gallium citrate complexes appears important
      especially in the renal cortex and bone.

PMID- 9630425
TI  - Bioavailability, absorption mechanism, and toxicity of microencapsulated iron (I)
      sulfate: studies in mice.
AB  - The iron compounds used for food fortification have to meet certain requisites
      related to their bioavailability, absorption mechanism, and toxicity, since they
      will be consumed by a massive population group. With these purposes, we evaluated
      a new product used for the iron fortification of milk and lacteous derivatives,
      called SFE-171, which is a ferrous sulfate, microencapsulated with phospholipids.
      The bioavailability studies were carried out using four groups of 30 female mice
      each. In two groups, we studied the absorption of ferrous ascorbate and ferrous
      sulfate, both in water as reference standards, which show absorptions of 13.1+/
      4.9% and 13.2+/-4.3%, respectively. With the third group, we studied the
      absorption of ferrous sulfate in milk; its value, 7.9+/-3.2%, is significantly
      lower than that of the remaining groups, with a p < 0.01. The studies with SFE
      171 in milk, were performed on the fourth group, with a result of 11.6+/-4.5%,
      demonstrating that its absorption does not differ significantly from that of the
      reference standards. The absorption mechanism was determined by means of in vivo
      self-displacement studies of the ferrous ion and the SFE-171, taking ferrous
      sulfate as the reference compound. For this study, 210 female mice were used, and
      no significant difference between the absorption mechanism of both products could
      be observed. Toxicity studies of the new product with regard to ferrous sulfate
      were carried out with two groups of 70 female mice each and two groups of 70 male
      mice each. The lethal dose 50% LD50 for SFE-171 and for ferrous sulfate was 1200
      and 680 mg/kg for female mice and 1230 and 670 mg/kg for male mice, respectively,
      demonstrating that the toxicity of the first product is substantially lower than
      that of the reference standard. We conclude that the iron product under study has
      a high bioavailability, an absorption mechanism equal to that of nonhemic iron,
      and lower toxicity than ferrous sulfate.

PMID- 9630426
TI  - Microphthalmia (mi) mice display an aberrant bone trace element composition.
AB  - It has been recognized that bone trace element composition analysis provides
      clues when analyzing bone-related physiological conditions. Increasing numbers of
      bone-related genetic diseases have been identified recently. In this study, we
      have analyzed bone trace element composition in a genetic mutant animal model.
      Mutations in the mouse microphthalmia (mi) gene affect the development of a
      number of cell types, including melanocytes, mast cells, and osteoclasts.
      Previous studies have shown that different alleles of the mi locus show
      osteopetrosis. In order to gain insights into the effects of a particular genetic
      defect on bone trace element composition and bone structure, we performed bone
      trace element composition analysis using inductively coupled plasma atomic
      emissions spectrometry (ICP-AES). Marked changes in bone trace element levels
      were found in vertebrate bones of mi mutant mice. The implications and possible
      applications of bone trace element analysis will be discussed in this article.

PMID- 9630427
TI  - Iron bioavailability from diets containing isolated or intact sources of lignin.
AB  - Experiments were conducted to determine effects of isolated lignin and intact
      lignin in foods on bioavailability of intrinsic iron in lignin-containing foods
      and of supplemental iron (FeSO4.H20). Standard curve and slope ratio methodology
      were employed to determine iron bioavailability to chicks. In one experiment,
      lignin content of foods ranged from 2 to 25% and iron bioavailability ranged from
      -20 to 140%, but no association between lignin content and bioavailability
      existed. In other experiments, increasing dietary lignin concentration from some
      natural sources reduced total iron availability, whereas increasing isolated
      lignin concentration had no effect. These results suggest that lignin structure
      or other unidentified factors determine intrinsic iron availability. No lignin
      source significantly decreased supplemental iron bioavailability.

PMID- 9630428
TI  - Chromium in a series of Portuguese plants used in the herbal treatment of
      diabetes.
AB  - Chromium (Cr3+) is an essential micronutrient for humans. Its main action is
      thought to be the regulation of blood sugar, because chromium deficiency is
      associated with diabetic-like symptoms, and chromium supplementation is
      correlated with increased glucose tolerance and insulin sensitivity. Some
      Portuguese aromatic plants are utilized as tisanes by diabetic people as
      medicinal plants. Their active principle is not yet known, and the importance of
      their chromium content in the claimed therapeutic properties should not be
      discarded. Therefore, determination of chromium in some Portuguese medicinal
      plants was performed by flameless atomic absorption. All the analyzed plants
      contain chromium at the normal level for this element, but the plants used to
      prepare tisanes to help diabetic conditions contain higher levels (2.2 microg/g
      dry wt+/-0.88; n=11) than the others (0.88 microg/g dry wt+/-0.18; n=17).

PMID- 9630429
TI  - Trace elements in Alzheimer's disease pituitary glands.
AB  - Levels of mercury (Hg), selenium (Se), iron (Fe), rubidium (Rb), and zinc (Zn)
      were measured in the pituitary gland to assess the possibility of a potential
      difference in the environmental Hg exposure of Alzheimer's disease (AD) patients
      and control subjects and levels of other elements of interest in AD. The
      pituitary gland has been established as a good predictor of environmental Hg
      exposure. Neutron activation analysis was utilized to determine levels of these
      elements in pituitary glands of 43 AD subjects and 15 control subjects. No
      significant differences were observed between the AD and control means for these
      five elements. The sole significant Pearson's correlation involving Hg was the
      established correlation with Se, indicative of the detoxification of Hg. The
      absence of a statistical difference between AD and control pituitary gland Hg
      levels suggests AD patients do not have an excessive environmental exposure to Hg
      compared to controls.

PMID- 9630430
TI  - ATP in cellular calcium-overload by trivalent metal ions.
AB  - Extracellular Ca2+-influx induced by trivalent metal ions (Fe3+, Al3+, Cr3+,
      In3+, Ga3+, and La3+) in Ehrlich carcinoma cells is enhanced by ATP. This action
      seems to be related to the high coordination capacity of the ATP ligand that
      inhibits the polymerization of the solvated cations taking place at physiological
      pH, and consequently permits their biological activity. A general relationship
      between induced lipid peroxidation and increased calcium uptake was not found.
      These results emphasize the ATP role in the toxicity of trivalent metals, and its
      possible involvement, via cellular calcium overload, in a neurodegenerative
      process, such as Alzheimer's and Parkinson's diseases, in whose etiology the
      implication of aluminum and iron has been suggested.

PMID- 9630431
TI  - Calcium/calmodulin-dependent protein kinase II involvement in release of
      gonadotropin-releasing hormone.
AB  - Involvement of calcium/calmodulin-dependent protein kinase II (CaM kinase II) in
      regulation of GnRH release was tested by determining the effect of CaM kinase II
      antagonists (KN-62 or KN-93) on GnRH release from rat or cattle infundibular
      (stalk median eminence) explants. Preincubation of male rat infundibular explants
      for 30 min with KN-62 (0.5, 1, 5 or 10 microM) 1.5 h prior to the addition of
      59.3 mM (high) K+ resulted in a dose-dependent suppression of GnRH release. A
      longer pretreatment period (2 h) of rat infundibular explants with KN-62 (1 or 10
      microM) appeared to enhance the suppressive effect of the CaM kinase II
      antagonist. Exposure (2 h) of rat infundibular explants to 10 microM, but not 0.1
      microM KN-93, resulted in a complete inhibition of high K+-induced GnRH release.
      Exposure of steer infundibular explant halves to KN-62 (50 or 100 microM) or KN
      93 (50 microM) inhibited high K+-induced GnRH release. Likewise, treatment of
      heifer infundibular explant halves with KN-93 (50 microM) abolished high K+
      induced GnRH release. The period of exposure required for KN-62 to elicit its
      effect was relatively short since exposure of KN-62 (100 microM) for only 91-150
      min of incubation was sufficient to block high K+-induced GnRH release from steer
      infundibular explant halves. In conclusion, these results: (1) support the
      hypothesis that CaM kinase II is involved in GnRH release from the rat and cattle
      infundibulum, (2) demonstrate that the effect of CaM kinase II on GnRH release
      from cattle infundibula is independent of reproductive state, (3) confirm
      previous reports supporting Ca2+ and CaM involvement in GnRH release from rat and
      cattle infundibula and (4) establish that infundibular explants incubated in
      vitro are useful for studying selected mechanisms regulating hypothalamic
      neurohormone release from neuron terminals.

PMID- 9630432
TI  - A naturally occurring basically charged human follicle-stimulating hormone (FSH)
      variant inhibits FSH-induced androgen aromatization and tissue-type plasminogen
      activator enzyme activity in vitro.
AB  - It is well known that deglycosylation of gonadotropins by enzymatic or chemical
      procedures or by deletion of sites for N-linked glycosylation produces
      antagonistic analogs which are able to interact strongly with the receptor and to
      inhibit binding of the wild-type hormone. In the present study, we analyzed the
      antagonistic properties of a naturally occurring basic follicle-stimulating
      hormone (FSH) charge isoform obtained after high-resolution chromatofocusing of
      human anterior pituitary glycoprotein extracts. Coincubation of increasing
      amounts of this isoform with a highly purified human pituitary FSH preparation or
      with recombinant human FSH at doses equivalent to their corresponding ED50 for
      estradiol and tissue-type plasminogen activator (tPA) production, inhibited FSH
      induced estrogen production and tPA enzyme activity by cultured rat granulosa
      cells in a dose-dependent manner. These inhibitory effects were apparently
      exerted at steps following 3',5'-cyclic adenosine monophosphate (cAMP) formation
      and did not involve activation of the protein kinase C pathway since: (a) at low
      doses, this basic FSH isoform moderately increased FSH-induced cAMP production by
      cultured rat granulosa cells; (b) coincubation of the antagonist isoform with
      dibutyryl cAMP completely inhibited the effects of this cAMP analog on estrogen
      and tPA production; (c) the isoform was able to stimulate production of cAMP in a
      human fetal cell line expressing the recombinant human FSH receptor, and (d) the
      inhibitory effects of the isoform were not affected by staurosporine, a protein
      kinase C inhibitor. The effects of this isoform upon dibutyryl cAMP-induced
      estrogen and tPA production were blocked by the addition of a highly specific
      antibody directed against human FSH, further demonstrating that the antagonistic
      effects observed were due to FSH-like molecules. In contrast to the inhibitory
      effects exhibited by this basic FSH isoform, a more acidic FSH charge variant
      consistently acted as an agonist of pituitary and recombinant FSH on both
      estrogen production and induction of tPA enzyme activity. These results indicate
      that the anterior pituitary gland normally produces FSH isoforms which act as
      either agonists or antagonists of FSH at the target cell level.

PMID- 9630433
TI  - Blockade of the oestrogen-induced luteinizing hormone surge in ovariectomized
      ewes by a highly selective opioid mu-receptor agonist: evidence for site of
      action.
AB  - Endogenous opioid systems in the hypothalamus inhibit gonadotropin-releasing
      hormone (GnRH) secretion, and a reduction in this inhibitory input
      (disinhibition) is thought to be part of the neural mechanism of the preovulatory
      GnRH/luteinizing hormone (LH) surge. We showed previously that
      intracerebroventricular infusion of the highly specific opioid mu-receptor
      agonist DAMGO delayed the oestrogen-induced LH surge in ovariectomized (OVX)
      ewes, whereas both delta- and kappa-agonists were ineffective. The aim of the
      present study was to establish the anatomical site of this effect. The most
      likely hypothalamic sites of action are the medial preoptic area (MPOA), where
      most GnRH perikarya are located in sheep, and/or the median eminence (ME), where
      GnRH fibres terminate on hypophysial portal blood vessels. Conscious,
      unrestrained OVX ewes with permanent bilateral guide tubes implanted into either
      the MPOA or the mediobasal hypothalamus (MBH), close to the ME, were injected
      (i.m.) with oestradiol benzoate (EB) 50 microg (t = 0 h). In this model, EB
      elicits a time-delayed surge in LH secretion after 13-19 h. Jugular venous blood
      was sampled at half-hourly intervals from -2 to 0 h, and from 10 to 26 h. From 12
      to 20 h, bilateral infusions of either the highly specific opioid mu-agonist
      DAMGO (40 nmol/h bilaterally) or saline were given into the MPOA or MBH at 2.5
      microl/h. Guide tube placements were confirmed histologically. The mean (+/- SEM)
      time to the onset of the LH surge was significantly (p < 0.01) increased in the
      animals (n = 9) that received DAMGO infusion into the MPOA (20.5 +/- 1.4 vs. 15.7
      +/- 0.6 h in the saline-infused controls). The effect was clearly apparent in 6/9
      of the DAMGO-infused animals. The mean (+/- SEM) time to LH surge onset was also
      significantly (p < 0.01) increased in the animals (n = 8) that received DAMGO
      infusion into the MBH (19.7 +/- 1.2 vs. 14.3 +/- 0.5 h). In this case, the effect
      was clearly apparent in 4/8 of the DAMGO-infused animals. We conclude that
      bilateral infusion of DAMGO into either the MPOA or the MBH can delay the EB
      induced LH surge in OVX ewes. These data provide further evidence for dual
      hypothalamic sites of opioid regulation of GnRH secretion, and are consistent
      with the hypothesis that disinhibition from opioid tone at both the MPOA and
      MBH/ME is permissive of the preovulatory GnRH/LH surge.

PMID- 9630434
TI  - Chronic melatonin treatment counteracts glucocorticoid-induced dysregulation of
      the hypothalamic-pituitary-adrenal axis in the rat.
AB  - Transient exposure of rats to high doses of dexamethasone (DEX; 500 microg/day
      for 5 days) produced a host of symptoms that are indicative of hypothalamic
      pituitary-adrenal (HPA) axis dysregulation, such as increased adrenocortical
      secretion over 24 h, blunted and prolonged secretory response to emotional
      stress, refractoriness of adrenocorticotropin in vitro release to stimulation
      with the secretagogues corticotropin-releasing hormone (CRH) and vasopressin,
      decreased levels of mRNA encoding type II corticosteroid receptors in the
      hippocampus and increased numbers of transcripts encoding CRH in the
      paraventricular nucleus. Daily administration of melatonin (MEL; 80 microg/kg)
      concomitantly with, and for 5 days after discontinuation of, glucocorticoid
      treatment 'normalized' most of the symptoms of impaired HPA regulation caused by
      the exposure to DEX. While none of the treatments used caused major shifts in
      circadian patterns of corticosterone secretion, MEL administration was associated
      with diminished overall corticosterone secretion and increased sensitivity to
      glucocorticoid feedback. Taken together, these findings indicate that chronic MEL
      treatment may protect several regulatory components of the HPA axis from
      glucocorticoid-induced deterioration.

PMID- 9630435
TI  - Effect of glutamate receptor agonists on catecholamine secretion in bovine
      chromaffin cells.
AB  - In this study, the effects of glutamate and glutamate receptor agonists in
      cultured chromaffin cells from bovine adrenal medulla were investigated. It was
      found that glutamate increases basal catecholamine (CA) secretion in a dose
      dependent manner. This effect is mimicked by specific agonists of the four known
      glutamate receptors N-methyl-D-aspartate (NMDA), quisqualate/(RS)-amino-3-hydroxy
      5-methyl-4-isoxazolepropionic acid (AMPA), kainate (KA), and trans-(+)-1-amino
      1,3-cyclopentane dicarboxylic acid (t-ACPD), which increased both basal and
      nicotine-evoked CA secretion. The NMDA receptor antagonist 2-amino-5
      phosphonopentanoic acid, 6-cyano-7-nitroquinoxaline-2,3-dione, an antagonist of
      KA and AMPA receptors, and L-(+)-2-amino-3-phosphonopropionic acid, an antagonist
      of the t-ACPD receptor, inhibited the stimulatory effect of related glutamate
      agonists. Hexamethonium, an antagonist of the nicotinic receptor, failed to
      influence glutamate agonists except for a 15% inhibition of KA. The increase in
      CA secretion produced by a 100 microM concentration of glutamate agonists was
      about 20-60% of that obtained with 10 microM of nicotine, an agonist of the
      physiological stimulatory cholinergic receptor. The increase in CA secretion
      produced by glutamate was accompanied by both an increase in bisoxonol
      fluorescence, suggesting membrane depolarization, and by an increase in
      intracellular Ca2+ concentrations. Results obtained with image analysis on single
      cells indicated that the percentage of cells which respond to the stimulation of
      50 microM of glutamate is 42%. From these results, we conclude that glutamate,
      through its four known glutamate receptors, can increase both basal and nicotine
      evoked CA secretion in chromaffin cells by a process which involves membrane
      depolarization and an increase in intracellular calcium levels.

PMID- 9630436
TI  - Molecular cloning and characterization of a highly basic protein, IA-4, expressed
      in pancreatic islets and brain.
AB  - A substraction library was constructed from mouse insulinoma (betaTC-1) and
      glucagonoma (alphaTC-1) cell lines. Differential screening and sequencing
      revealed a novel cDNA clone, IA-4, which was expressed in the islets of
      Langerhans and the brain. IA-4 cDNA is 1,007 bp in length and predicts a protein
      of 187 amino acids with a molecular mass of 19,940 D. Examination of the amino
      acid sequence showed a high content of arginine (18.7%), proline (14.4%), alanine
      (16.0%), leucine (13.4%) and glycine (9.6%). The deduced pI value is 12.5
      indicating a highly basic protein. Northern blot analysis revealed a 1-kb mRNA
      highly expressed in brain, trigeminal ganglia and cell lines of neuroendocrine
      origin. Rabbit polyclonal antiserum raised against a synthetic IA-4 peptide,
      designated Pep-1, not only reacted with IA-4 recombinant protein, but also
      immunostained the islets of Langerhans and large neurons of the hippocampus,
      cerebral cortex, spinal cord, dorsal ganglia and Purkinje cells of the
      cerebellum. The high expression of IA-4 protein in neuroendocrine cells and its
      unique amino acid sequence suggest that IA-4 may have an important, but still
      undetermined, function in these special cell types.

PMID- 9630437
TI  - Quantitation and regulation of pyroglutamyl peptidase II messenger RNA levels in
      rat tissues and GH3 cells.
AB  - The distribution of the mRNA of the specific thyrotropin-releasing-hormone (TRH)
      degrading enzyme pyroglutamyl peptidase II (EC 3.4.19.6) in rat tissues and brain
      regions and its regulation in rat tissues and in GH3 cells was studied by a
      reliable and quantitative solution hybridization ribonuclease protection assay.
      The distribution of pyroglutamyl peptidase II mRNA levels was uneven with the
      highest level of mRNA found in brain. Within brain the distribution of
      pyroglutamyl peptidase II mRNA was heterogeneous. A single dose of T3 markedly
      increased the level of pyroglutamyl peptidase II mRNA in the pituitary (p < 0.01)
      and in the liver (p < 0.05). In GH3 cells, exposure to T3 at concentrations from
      10(-10) to 10(-6) M for time periods of 2-24 h, did not change pyroglutamyl
      peptidase II mRNA levels. Acute administration of TRH to rats had no effect on
      pyroglutamyl peptidase II mRNA levels. By contrast, TRH down-regulated
      pyroglutamyl peptidase II mRNA in GH3 cells. A similar effect was produced in GH3
      cells by activators of protein kinase C. These studies reveal fundamental
      differences in the mechanism of regulation of pyroglutamyl peptidase II mRNA in
      pituitary and in GH3 cells. Elevation of pyroglutamyl peptidase II mRNA in liver
      by T3 suggests that this organ is the source of the enzyme in serum.

PMID- 9630438
TI  - Chlorination of drinking water and cancer mortality in Taiwan.
AB  - Chlorination has been the major strategy for disinfection of drinking water in
      Taiwan. An ecologic epidemiological study design was used to examine whether
      chlorination of drinking water was associated with cancer risks. A "chlorinating
      municipality" (CHM) was defined as one in which more than 90% of the municipality
      population was served by the chlorinated water while an "nonchlorinating
      municipality" (NCHM) was one in which less than 5% of the municipality population
      was served by chlorinated water. Age-adjusted mortality rates for cancer during
      1982-1991 among the 14 CHMs were compared to rates among the 14 matched NCHMs
      with similar urbanization level and sociodemographic characteristics. The results
      of this study suggest a positive association between consumption of chlorinating
      drinking water and cancer of the rectum, lung, bladder, and kidney. Although
      these findings must be interpreted with caution because of limitations in the
      ecological study design, their public health significance should not be
      disregarded because chlorination of water is so widely practiced in Taiwan.

PMID- 9630439
TI  - In vitro reduction kinetics of hexavalent chromium in human blood.
AB  - This study examines time- and concentration-dependent changes in distribution of
      hexavalent chromium [Cr(VI)] and total chromium [Cr-(TOT)] in reconstituted human
      blood following addition of potassium dichromate. Fresh human blood stabilized
      with EDTA was obtained from human volunteers soon after meal ingestion and at 2.5
      h after a light meal (herein defined as "2.5-h fasted" conditions). Cr(VI) spiked
      into plasma under 2.5-h fasting conditions at 3.0-12.5 micrograms/L was stable
      for several hours, indicating a lack of appreciable reductive capacity in
      isolated plasma. Spiked plasma following a recent meal exhibited immediate but
      variable reduction of Cr(VI) up to 300 micrograms/L. When the spiked plasma was
      recombined with the red blood cell (RBC) fraction, rapid reduction occurred in
      both the plasma and the RBC fractions based on measurement of Cr(VI) and Cr(TOT).
      The data indicate that plasma reduction capacity is enhanced by a recent meal,
      but may be overwhelmed at Cr(VI) concentrations between 2000 and 10,000
      micrograms/L. These data also suggest that the RBC fraction apparently has the
      capacity to reduce Cr(VI) at concentrations in blood up to 15,000 micrograms/L,
      and that the rate of Cr(VI) uptake into RBCs may not exceed the rate of
      intracellular reduction at these concentrations.

PMID- 9630440
TI  - Studies on oxidative damage induced by cyanobacteria extract in primary cultured
      rat hepatocytes.
AB  - Contamination of water by cyanobacteria (blue-green algae) is a serious health
      problem around the world, largely due to the toxic effects of microcystins, a
      group of potent hepatotoxins. However, the mechanisms responsible for the
      cytotoxicity of microcystins have not been fully elucidated. In the present
      study, oxidative damage caused by lyophilized freshwater cyanobacteria extract
      was evaluated on primary cultured rat hepatocytes. A time- and dose-dependent
      increase of lactate dehydrogenase (LDH) leakage was observed in hepatocytes
      treated with cyanobacteria extract. Lipid peroxidation, a main manifestation of
      oxidative damage, was also studied and a time- and dose-dependent increase in
      malondiadehyde was observed. In addition, by using a fluorescent probe, 2',7'
      dichlorofluorescein diacetate, it was found that cyanobacteria extract was able
      to enhance intracellular production of reactive oxygen species (ROS) in a dose-
      and time-dependent manner. Moreover, desferrioxamine, a specific iron chelator,
      could significantly decrease LDH leakage and ROS production caused by
      cyanobacteria extract treatment. These findings thus provide experimental
      evidence that oxidative damage is involved in cyanobacteria extract-induced
      hepatotoxicity. The understanding of this mechanism is believed to be beneficial
      to the prevention and control of the toxicity of microcystin and cyanobacteria
      contamination.

PMID- 9630441
TI  - Excretion of arsenic (As) in urine of children, 7-11 years, exposed to elevated
      levels of As in the city water supply in Hermosillo, Sonora, Mexico.
AB  - Arsenic (As) is a common element in the environment with many industrial uses,
      but it also can be a contaminant in drinking water and present serious health
      concerns. Earlier studies on the quality of drinking water in the city of
      Hermosillo, Sonora, Mexico, showed high levels of As (> 0.05 ppm) in water from
      wells located in the northern part of the city. Additionally a high positive
      correlation between the levels of Fluoride (F) and As in the same wells was
      found. Therefore, the objective of this study was to determine the excretion of
      As in children, 7-11 years of age, that had been exposed to elevated levels of As
      in their drinking water. Twenty-four-hour urine samples and a water sample taken
      directly in the home were collected from school age children living in two
      different areas with known high levels of As in their drinking water. A control
      group with normal levels of As in their water was also included. As was
      determined by an atomic absorption-hydride generator, verified with the use of
      NBS certified standards (SRM 1643a and SRM 2670). None of the water samples
      exceeded the limit established for drinking water; however, there was a
      significant difference between the intake of As and the As in drinking water
      among the three areas of the study. Average As in water was 0.009 +/- 0.002 and
      0.030 +/- 0.011 micrograms/ml between the control and high areas. Intake (in
      micrograms/day) was 15 +/- 3 and 54 +/- 18. In the group consuming water with
      high levels of As, 65% of the children exceeded the recommended dose of < 1
      micrograms/kg/day (EPA, 1988). Several children in this study also had high
      levels of As in their urine. Even though As levels in the drinking water are
      within the norms, it appears that children exposed to high levels of As in their
      drinking water may have a health risk.

PMID- 9630442
TI  - Dissolution of short and long rockwool and glasswool fibers by macrophages in
      flowthrough cell culture.
AB  - Dissolution of MMVF (man-made vitreous fibers) by macrophages has previously been
      studied utilizing cell cultures in wells. A new, more dynamic method has been
      developed to explore the effects of macrophages on MMVF dissolution. In this
      method, the culture medium flows through a membrane on which the macrophages and
      fibers are placed. The dissolution of short and long rockwool and glasswool
      fibers was investigated in the present study by macrophages by assessing the
      dissolution of Si (silicon), Fe (iron), and Al (aluminium) from the fibers.
      Dissolution of these elements usually increased as a function of time. Generally,
      the dissolution of elements from the fibers in the flowthrough culture exceeded
      that observed with the culture in wells system. The dissolution of glasswool
      fibers was greater in medium than in cell culture, whereas the opposite was true
      for rockwool fibers. Dissolution of Si was greater from glasswool than from
      rockwool fibers, while the opposite was true for Fe and Al. Macrophages that had
      phagocytized fibers in flowthrough culture contained Si, and there were also
      precipitations with Si in the samples. The fibers in the flowthrough culture also
      exhibited surface changes such as breakings, pittings, etching, and peeling. The
      short rockwool fibers tended to fracture more than short glasswool fibers, while
      long glasswool fibers were more extensively broken than short glasswool fibers.
      The results with this new, dynamic, flowthrough culture method with macrophages
      demonstrate that this method provides valuable information on the abilities of
      macrophages to dissolve MMVF leading to subsequent morphological changes of
      fibers.

PMID- 9630443
TI  - An overview of the role of mineral solubility in silicosis and asbestosis.
AB  - Asbestosis and silicosis are fibrotic diseases initiated by the inhalation of
      silica-containing dusts, asbestos and quartz. There are various approaches for
      explaining the causes of these diseases. At present, our knowledge on the matter
      indicates that silicic acid dissolved from these minerals, contact between
      macrophages and minerals, highly reactive and oxidative species formed on the
      mineral surface, and lysosomal enzymes released upon engulfment of particulate
      mineral of appropriate size all contribute to various extents to the initiation
      of fibrosis. Among these mineral solubility seems to have a substantial
      contribution as a causative factor.

PMID- 9630444
TI  - Correlation between the amounts of polycyclic aromatic hydrocarbons and
      mutagenicity of airborne particulate samples from Taichung City, Taiwan.
AB  - Taichung is the largest city in the central part of Taiwan, and its air pollution
      problems are similar to those in other large cities around the world. To evaluate
      the potential of the air pollution and identify major pollutant sources in this
      city, 181 airborne particulate samples were collected biweekly from seven
      locations around Taichung over an entire year. The mutagenicity of acetone
      extracts of the air samples was evaluated using the Salmonella/microsomal test
      with Salmonella typhimurium TA98 in the presence and absence of S9 mixtures. The
      air samples from September 1994 showed the highest direct and indirect
      mutagenicity among the 12 months, whereas those from October and June had the
      lowest direct and indirect mutagenicity, respectively. To elucidate the
      correlation between mutagenicity and polycyclic aromatic hydrocarbons (PAHs),
      high-performance liquid chromatography was used to determine the amount of each
      of 10 PAHs in the air samples. Among the 10 PAHs, the monthly average amount of
      B[g,h,i]P in the samples was the highest, followed by B[a]FA, B[a]P, and B[k]FA.
      Linear regression analysis showed a positive correlation between monthly average
      total amounts of PAHs and indirect mutagenicity. The monthly average amount of
      B[g,h,i]P was correlated more with indirect mutagenicity than with other PAHs.
      B[g,h,i]P is an indicator PAH emitted from both diesel and gasoline engine
      exhaust. Thus, we suggest that mobile air pollutant sources in Taichung City may
      be more significant than stationary ones. Moreover, B[g,h,i]P seems to act as a
      mutagenicity indicator compound in air samples from Taichung City.

PMID- 9630445
TI  - Autonomic function in manganese alloy workers.
AB  - The observation of orthostatic hypotension in an index case of manganese toxicity
      lead to this prospective attempt to evaluate cardiovascular autonomic function
      and cognitive and emotional neurotoxicity in eight manganese alloy welders and
      machinists. The subjects consisted of a convenience sample consisting of an index
      case of manganese dementia, his four co-workers in a "frog shop" for gouging,
      welding, and grinding repair of high manganese railway track and a convenience
      sample of three mild steel welders with lesser manganese exposure also referred
      because of cognitive or autonomic symptoms. Frog shop air manganese samples 9.6
      10 years before and 1.2-3.4 years after the diagnosis of the index case exceeded
      1.0 mg/m3 in 29% and 0.2 mg/m3 in 62%. Twenty-four-hour electrocardiographic
      (Holter) monitoring was used to determine the temporal variability of the
      heartrate (RR' interval) and the rates of change at low frequency (0.04-0.15 Hz)
      and high frequency (0.15-0.40 Hz). MMPI and MCMI personality assessment and short
      term memory, figure copy, controlled oral word association, and symbol digit
      tests were used. The five frog shop workers had abnormal sympathovagal balance
      with decreased high frequency variability (increased ln LF/ln HF). Seven of the
      eight workers had symptoms of autonomic dysfunction and significantly decreased
      heart rate variability (rMSSD) but these did not distinguish the relative
      exposure. Mood or affect was disturbed in all with associated changes in short
      term memory and attention in four of the subjects. There were no significant
      correlations with serum or urine manganese. Power spectrum analysis of 24-h
      ambulatory ECG indicating a decrease in parasympathetic high frequency activation
      of heart rate variability may provide a sensitive index of central autonomic
      dysfunction reflecting increased exposure to manganese, although the contribution
      of exposures to solvents and other metals cannot be excluded. Neurotoxicity due
      to the gouging, welding, and grinding of mild steel and high manganese alloys (11
      25%) merits air manganese and neuropsychologic surveillance including autonomic
      function by Holter monitoring of cardiovagal activation.

PMID- 9630446
TI  - Effects of smoking, aromatic amines, and chromates on CD4+ and CD8+ T lymphocytes
      in male workers.
AB  - To investigate effects of smoking, aromatic amines (AAs), and chromates (CRs) on
      T lymphocyte subpopulations, we measured CD3+, CD4+, and CD8+ T lymphocytes in
      the peripheral blood of 33 nonexposed workers, 25 AA-use workers, 27 AA
      production workers, and 19 CR workers (all subjects were males). The number of
      CD4+ T lymphocytes in smokers of nonexposed workers was significantly larger than
      that of the nonsmokers; also, the numbers of CD4+ and CD3+ T lymphocytes in
      smokers of each group of AA-production and AA-use workers were significantly
      larger than those in nonsmokers. Number of CD4+ and CD3+ T lymphocytes in
      nonsmokers of AA-production and CR workers were significantly smaller than those
      in nonsmokers of nonexposed workers; the number of CD8+ T lymphocytes in
      nonsmokers of CR workers was significantly smaller than that in nonsmokers of
      nonexposed workers. The cross-sectional study suggests that (1) smoking increases
      CD4+ (and CD3+) T lymphocytes in all categories of workers except for CR workers;
      (2) exposure to CRs and AAs decreases CD4+ (and CD3+) T lymphocytes; (3) the
      magnitude of decrease in CD4+ T lymphocytes is large among CR workers,
      intermediate among AA-production workers, and small among AA-use workers
      regardless of smoking status; and (4) exposure to CRs also decreases CD8+ T
      lymphocytes.

PMID- 9630447
TI  - Computer simulation of inspiratory nasal airflow and inhaled gas uptake in a
      rhesus monkey.
AB  - There is increasing evidence that inspiratory airflow patterns play a major role
      in determining the location of nasal lesions induced in rats by reactive, water
      soluble gases such as formaldehyde and chlorine. Characteristic lesion patterns
      have also been seen in inhalation toxicity studies conducted in rhesus monkeys,
      the nasal anatomy of which resembles that of humans. To examine the hypothesis
      that regions of high airflow-dependent uptake and lesions occur in similar nasal
      locations in the primate, airflow and gas uptake patterns were simulated in an
      anatomically accurate computer model of the right nasal airway of a rhesus
      monkey. The results of finite-element simulations of steady-state inspiratory
      nasal airflow for the full range of resting physiological flow rates are
      reported. Simulated airflow patterns agreed well with experimental observations,
      exhibiting secondary flows in the anterior nose and streamlined flow posteriorly.
      Simulated airflow results were used to predict gas transport to the nasal passage
      walls using formaldehyde as an example compound. Results from the uptake
      simulations were compared with published observations of formaldehyde-induced
      nasal lesions in rhesus monkeys and indicated a strong correspondence between
      airflow-dependent transport patterns and local lesion sites. This rhesus computer
      model will provide a means for confirming the extrapolation of toxicity data
      between species by extrapolating rat simulation results to monkeys and comparing
      these predictions with primate lesion data.

PMID- 9630448
TI  - Diet restriction enhances compensatory liver tissue repair and survival following
      administration of lethal dose of thioacetamide.
AB  - Diet restriction is known to prevent a plethora of age-associated diseases
      including cancer. However, the effects of diet restriction on noncancer end
      points are not known. The objective of this study was to investigate whether diet
      restriction protects against hepatotoxicity of thioacetamide (TA), and if so, to
      investigate the underlying mechanism. Male Sprague-Dawley rats (250-275 g) were
      maintained on 65% of their ad libitum (AL) food consumption for a period of 3
      weeks and then treated with a single low dose of 50 mg TA/kg i.p.. Plasma enzymes
      (ALT and SDH), hepatic glycogen levels, and 3H-thymidine incorporation into
      hepatocellular nuclear DNA were measured during a time course (0-120 h) after TA
      administration. Liver sections were examined for histopathology, and cell-cycle
      progression was assessed by proliferating cell nuclear antigen (PCNA)
      immunohistochemistry. In AL rats hepatic necrosis was evident at 12 h, peaked at
      36 h, persisted up to 72 h, and was resolved by 96 h. In the diet-restricted (DR)
      group hepatic necrosis was observed at 12 h, peaked at 24 h, persisted till 72 h,
      and was resolved by 96 h. Maximal injury indicated by enzyme elevation occurred
      in DR rats and was approximately sixfold greater than that observed in the AL
      group. Histopathological examination of the liver sections revealed liver injury
      concordant with plasma enzyme elevations. There was a higher and sustained S
      phase synthesis in the DR rats compared to AL group. S-phase stimulation was
      evident at 36 h, peaked at 48 h, and persisted until 96 h in the DR rats, whereas
      in the AL rats peak S-phase stimulation occurred at 36 h and subsided by 72 h.
      PCNA studies revealed a corresponding stimulation of cell-cycle progression
      indicating highly stimulated compensatory tissue repair. The 14-day lethality
      experiments (600 mg TA/kg i.p.) indicated 70% survival in the DR rats compared to
      10% survival in the AL group. Although diet restriction increases hepatotoxic
      injury of TA, it protects from the lethal outcome by enhanced liver tissue
      repair. Comparison of liver injury and tissue repair employing an equitoxic dose
      (600 mg TA/kg in AL rats yields similar liver injury as observed with 50 mg TA/kg
      in DR rats) revealed that in spite of near equal injury up to 36 h, tissue repair
      response in DR rats is much higher. The compensatory tissue repair allows the DR
      rats to escape death in contrast to much lower compensation in AL rats leading to
      progression of liver injury culminating in death.

PMID- 9630449
TI  - Enhanced regional expression of glutathione S-transferase P1-1 with colocalized
      AP-1 and CYP 1A2 induction in chlorobenzene-induced porphyria.
AB  - A distinct, nonfocal expression pattern was observed for glutathione S
      transferase P1-1 (rGSTP1-1) in rats exposed to either hexachloro-(HCB) or
      pentachlorobenzene (PeCB). The nonfocal expression was localized to the
      centrilobular region with the most intense staining nearest the central vein. A
      Western blot analysis revealed a 5- and 15-fold induction of rGSTP1-1 with PeCB
      and HCB treatment on an equal molar basis, respectively. Evaluation of porphyrin
      fluorescence also revealed a centrilobular accumulation with average porphyrin
      measurements of 0.319, 0.590, and 0.206 micrograms/g tissue for PeCB, HCB, and
      corn-oil controls, respectively. Due to the role of Activator Protein-1 (AP-1) in
      rGSTP1-1 expression and CYP 1A2 in the pathogenesis of porphyria cutanea tarda,
      immunohistochemical localization of c-jun, c-fos, and CYP 1A2 was also performed.
      Increased expression and colocalization within the liver lobule was observed for
      c-jun, c-fos, CYP 1A2, rGSTP1-1, and areas of porphyrin accumulation. These
      observations are consistent with studies that have associated the induction of
      GST-P with jun- and fos-related gene products.

PMID- 9630450
TI  - Effect of procaine hydrochloride on cyanide intoxication and its effect on
      neuronal calcium in mice.
AB  - Cyanide intoxication in mice can be antagonized by the local anesthetic, procaine
      HCI, either alone or in combination with sodium nitrite and/or sodium
      thiosulfate. Antitoxic potency, derived from LD50 values, was compared in groups
      of mice pretreated with sodium nitrite (43.9 mg/kg i.p.), sodium thiosulfate (1
      g/kg i.p.), and procaine HCI (37.0 mg/kg i.p.) either alone or in various
      combinations. The results of present study indicated that procaine HCI provides a
      significant protection against the lethal effects of potassium cyanide. Dose
      response studies revealed procaine hydrochloride pretreated 3 min before KCN, at
      doses of 18.48-73.9 mg/kg, produced significant elevation of KCN LD50, moreover
      it has a good dose-effect relationship, but its antidotal effect was weaker than
      sodium nitrite or sodium thiosulfate when they were administered alone. The
      protective effect of sodium nitrite and sodium thiosulfate was enhanced with
      procaine HCI. When procaine was administered in combination both with sodium
      nitrite and sodium thiosulfate, its protective effects were further enhanced. Its
      antitoxic potency is 6.22. The effects of procaine on antagonizing the cyanide
      induced whole-brain total calcium increase were also studied. KCN (7 mg/kg i.p.)
      significantly increased whole-brain total calcium level from 28.37 +/- 0.75 to
      48.05 +/- 1.06 mg/g dry wt within 30 min, which can be prevented by procaine
      pretreated 15 min before KCN. One of the possible mechanism of procaine on
      antagonizing cyanide toxicity seems, at least, related to its effect on
      inhibiting the cyanide-induced neuronal calcium increase and maintaining the
      homeostasis of neuronal calcium.

PMID- 9630451
TI  - The response of pulmonary vascular endothelial cells to monocrotaline pyrrole:
      cell proliferation and DNA synthesis in vitro and in vivo.
AB  - Monocrotaline pyrrole (MCTP) causes pulmonary vascular endothelial cell (EC)
      injury followed by progressive pulmonary vascular leak in vivo and the inhibition
      of EC proliferation in vitro. It was hypothesized that MCTP inhibits cell
      proliferation in vitro by interfering with cell cycle progression in a cycle
      phase-specific manner. Furthermore, it was proposed that early alterations in
      MCTP-induced lung injury leading to hypertension were associated with a similar
      inhibition of EC proliferation. Subconfluent cultures of bovine pulmonary artery
      endothelial cells (BECs) were synchronized with aphidicolin (APH), a reversible
      G1-S phase inhibitor. Upon removal of APH, BECs were exposed to MCTP (5
      micrograms/ml) or its vehicle for a 4-h interval corresponding to either the G1
      S, S-G2, or G2 through mitosis (M) phases of the cell cycle. Fluorescence
      activated cell sorting (FACS) was used to identify MCTP-induced changes in cell
      cycle progression in BECs, and the transit of S phase cells through the cycle was
      characterized through the incorporation of bromodeoxyuridine (BrdU). Synchronized
      BECs exposed to MCTP between mid-S-G2 or G2 through M were briefly delayed in G2
      M at 12 h but underwent cell division by 24 h. By contrast, BECs treated with
      MCTP immediately after release from APH block became arrested in G2-M at 24 h and
      showed evidence of continued DNA synthesis and hypertetraploidy, but they did not
      divide. In vivo, MCTP (3.5 mg/kg i.v.) administration caused an increase in
      arterial EC BrdU incorporation between Days 3 and 7, but no increase in EC
      density. During this same interval, pulmonary vascular permeability increased and
      persisted. In summary, MCTP inhibits cell proliferation in a cell cycle phase
      dependent manner in vitro. The results suggest that a similar mechanism could
      occur in vivo and may be associated with delayed EC repair, a process that could
      contribute to persistent pulmonary vascular leak.

PMID- 9630452
TI  - Glutathione conjugation of perchloroethylene in rats and mice in vitro: sex-,
      species-, and tissue-dependent differences.
AB  - Perchloroethylene (Per)-induced nephrotoxicity and nephrocarcinogenicity have
      been associated with metabolism by the glutathione (GSH) conjugation pathway to
      form S-(1,2,2-trichlorovinyl)glutathione (TCVG). Formation of TCVG was determined
      in incubations of Per and GSH with isolated renal cortical cells and hepatocytes
      from male and female Fischer 344 rats and with renal and hepatic cytosol and
      microsomes from male and female Fischer 344 rats and B6C3F1 mice. The goal was to
      assess the role of metabolism in the sex and species dependence of susceptibility
      to Per-induced toxicity. A key finding was that GSH conjugation of Per occurs in
      kidney as well as in liver. Although amounts of TCVG formation in isolated kidney
      cells and hepatocytes from male and female rats were generally similar, TCVG
      formation in subcellular fractions showed marked sex, species, and tissue
      dependence. This may be due to the presence of multiple pathways for metabolism
      in intact cells, whereas only the GSH conjugation pathway is active in the
      subcellular fractions under the present assay conditions. TCVG formation in
      kidney and liver subcellular fractions from both male rats and mice were
      invariably higher than corresponding values in female rats and mice. Amounts of
      TCVG formation in rat liver subcellular fractions were approximately 10-fold
      higher than in corresponding fractions from rat kidney. Although rats are more
      susceptible to Per-induced renal tumors than mice, amounts of TCVG formation were
      7- to 10-fold higher in mouse kidney subcellular fractions and 2- to 5-fold
      higher in mouse liver subcellular fractions of both sexes compared to
      corresponding fractions from the rat. Hence, although the higher amounts of TCVG
      formation in liver and kidney from male rats correspond to their higher
      susceptibility to Per-induced renal tumors compared with female rats, the
      markedly higher amounts of TCVG formation in mice compared with rats suggest that
      other enzymatic or transport steps in the handling of Per in mice contribute to
      their relatively low susceptibility to Per-induced renal tumors

PMID- 9630453
TI  - Comparison of ozone-induced effects on lung mechanics and hemodynamics in the
      rabbit.
AB  - The effects of rabbit exposure to ozone (O3)(0.4 ppm for 4 h) on pulmonary
      mechanical properties and hemodynamics have been investigated on the isolated
      perfused lung model. Tracheal pressure, airflow, and tidal volume were measured
      in order to calculate lung resistance (RL) and dynamic compliance (Cdyn). Using
      the arterial/venous/double occlusion method, the total pressure gradient
      (deltaPT) was partitioned into four components (arterial, pre-, postcapillary and
      venous). Dose-response curves to acetylcholine (ACh), substance P (SP), and
      histamine were constructed in lungs isolated from rabbits immediately or 48 h
      after air or O3 exposure O3 induced a significant increase in the baseline value
      of deltaPt, more markedly 48 h after the exposure. Immediately after the
      exposure, O3 partly inhibited the ACh-, SP-, and histamine-induced decreases in
      Cdyn and increases in RL. This inhibitory effect was still in part present 48 h
      after O3 treatment. In the groups studied immediately after exposure, O3 did not
      significantly modify the ACh-, SP-, and histamine-induced vasoconstriction. Forty
      eight hours after exposure, O3 induced a contractile response to ACh and SP in
      the arterial segment but decreased the response to histamine. We conclude that O3
      can induce direct vascular constriction. Directly, but also 48 h after exposure,
      O3 can inhibit the ACh-, SP-, and histamine-induced changes in lung mechanical
      properties. Ozone can also induce some changes in the intensity and in the
      location of the vascular responses to ACh, SP, and histamine.

PMID- 9630454
TI  - Endocrine factors modulate the phenobarbital-mediated induction of cytochromes
      P450 and phase II enzymes in a similar strain-dependent manner.
AB  - Phenobarbital (PB)-mediated induction of five forms of cytochrome P450 (CYP2B1,
      CYP2B2, CYP3A1, CYP2A1, and CYP2C6) and epoxide hydrolase is highly suppressed,
      at the transcriptional level, in Wistar Furth (WF) relative to Fischer 344 (F344)
      female rats. Either hypophysectomy or thyroid hormone depletion by methimazole
      largely reverses the suppression in WF animals. Here we show that this strain
      dependent polymorphism and unusual endocrine regulation extend to PB induction of
      phase II enzymes UGT2B1 uridine diphosphate-glucuronosyl transferase (UDPGT), PB
      inducible aldehyde dehydrogenase (ALDH), and glutathione transferases Ya1 and Ya2
      (GSTYa1 and GSTYa2). UDPGT, ALDH, GSTYa1, and GSTYa2 had mRNA levels induced by
      PB in a similar strain-dependent manner (F344 > WF). The extent to which mRNA
      induction was favored in female F344 relative to female WF was gene dependent
      (UDPGT 5 x; ALDH 15 x; GSTYa1 2 x; GSTYa2 3-5 x). Again, thyroid suppression by
      methimazole treatment selectively enhanced mRNA induced levels in female WF
      animals to remove much of the strain difference. Since thyroid hormone action is
      linked to fatty acid (FA) homeostasis, we tested the possibility that FAs
      participated in this endocrine polymorphism by using three isocaloric diets: low
      fat (LFD), polyunsaturated fatty acid (PUFAD), or saturated fatty acid (SFAD).
      The LFD suppressed PB-induction of CYP mRNA and protein in WF but not F344 rats.
      This had no parallel in phase II mRNA induction, possibly indicating that FA and
      thyroid hormone effects are uncoupled. We conclude that the PB-response mechanism
      for induction of multiple P450 and phase II genes share a pathway that has as a
      common feature the linkage between chemical stimulation and thyroid hormone
      suppression that is seen in female WF relative to female F344 rats but not in
      male rats.

PMID- 9630455
TI  - Renal hemodynamics in rats with cadmium-induced nephropathy.
AB  - Glomerular filtration rate (GFR) is known to decline in patients with cadmium
      (Cd)-induced nephropathy. However renal hemodynamics in Cd-induced nephropathy
      remain unknown. We investigated renal hemodynamics in experimental Cd-induced
      nephropathy. Male Sprague-Dawley rats were given 0.18 mg/rat of cadmium chloride
      i.p. three times a week for 3 and 16 months. Age-matched control rats were given
      physiological saline. Mean arterial pressures after 3 and 16 months were
      identical among the groups. In comparison with age-matched control rats,
      significant decreases in GFR associated with a significantly lower filtration
      fraction (FF) were demonstrated in both groups of Cd-treated rats, but the
      changes were more prominent in the 16-month Cd-treated rats. Renal plasma flow
      was significantly decreased in the 3-month Cd-treated rats whereas it was
      preserved in the 16-month Cd-treated rats because of anemia. Urinary sodium
      excretions in both groups of Cd-treated rats were significantly greater than
      those in the respective control rats. On light microscopic examination, only mild
      degeneration of tubular cells and interstitial edema in limited areas of the
      proximal tubules were observed in the 3-month Cd-treated rats. In the 16-month Cd
      treated rats multifocal tubular atrophy and interstitial fibrosis in the outer
      cortex were noted. Electron microscopic examinations revealed conspicuous
      degenerative changes in the proximal tubular epithelial cells, diffuse thickening
      of glomerular basement membranes, and foot process fusions in 16-month Cd-treated
      rats. These data suggested that the decline in GFR in the Cd-treated rats
      resulted mainly from the decline in FF, which might be functional rather than
      structural in origin and might be associated with proximal tubular dysfunctions.

PMID- 9630456
TI  - The role of liver alcohol dehydrogenase isoenzymes in the oxidation of
      glycolethers in male and female rats.
AB  - The glycolethers 2-methoxyethanol (2-ME), 2-ethoxyethanol (2-EE), and 2
      butoxyethanol (2-BE) are used as solvents and have teratogenic, spermatotoxic,
      and hematotoxic effects. These glycolethers are oxidized to their corresponding
      alkoxyacetic acids, probably by alcohol dehydrogenase (ADH) and aldehyde
      dehydrogenase (ALDH). This metabolic conversion of the glycolethers is a
      prerequisite for development of toxicity, as the toxic effects have been shown to
      be due to the alkoxyacetic acid metabolites. Three isoenzymes of ADH have been
      detected in rat tissues. The liver contains two of these isoenzymes, ADH-2 and
      ADH-3. It has also been shown that the activity level of ADH is strongly sex
      dependent, with higher activity in females than in males. In the present study,
      we have investigated whether one or both of the ADH isoenzymes in male and female
      rat livers were able to oxidize 2-ME, 2-EE, and 2-BE and whether one or both of
      the ADH isoenzymes in male rat liver were able to oxidize 2-pentyloxyethanol and
      2-hexyloxyethanol. Our results indicated that only the ADH-3 isoenzyme
      effectively oxidized the glycolethers in rat liver. Both ADH-2 and ADH-3 were
      able to oxidize medium chain aliphatic alcohols with a chain length corresponding
      to the glycolethers. The activity of ADH is higher in female than in male rat
      liver. However, it was the same ADH isoenzyme (ADH-3) that oxidized the different
      glycolethers tested in both male and female rat livers, and the substrate
      specificity was 2-BE > 2-EE > 2-ME.

PMID- 9630457
TI  - Toxicology and pharmacokinetics of DT388-GM-CSF, a fusion toxin consisting of a
      truncated diphtheria toxin (DT388) linked to human granulocyte-macrophage colony
      stimulating factor (GM-CSF) in C57BL/6 mice.
AB  - Because the majority of acute myeloid leukemia (AML) blasts express the
      granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor, we are
      developing a fusion toxin consisting of a truncated diphtheria toxin (DT388)
      linked to human GM-CSF for multi-drug resistant AML. Our goal was to determine
      the toxicity and pharmacokinetics of DT388-GM-CSF in C57BL/6 mice. Because human
      GM-CSF does not cross-react with the mouse GM-CSF receptor, the toxicity observed
      should be nonspecific toxicity of DT388. We injected C57BL/6 mice i.p. with 0.1,
      0.5, 1.0, 1.5, 1.75, 2.0, 3.5, 5.0, or 10 micrograms/day of DT388-GM-CSF for 5
      consecutive days. For pharmacokinetics, blood samples were drawn at 20, 40, 60,
      120, and 180 min after i.p. administration of 81 micrograms/kg of DT388-GM-CSF.
      In mice, the LD10 of DT388-GM-CSF is between 84.4 (1.5) and 104.4 (1.75)
      micrograms/kg (microgram) when administered for 5 consecutive days. All mice
      receiving > or = 201 micrograms/kg (3.5 micrograms) for 5 consecutive days died.
      Histopathologic examination of morbid animals showed only renal toxicity with
      acute proximal tubular necrosis. DT388-GM-CSF is stable in vivo based on
      nonreducing SDS-PAGE gel of plasma samples of 125I-labeled DT388-GM-CSF injected
      i.p.. The peak concentration of DT388-GM-CSF was 3.3 x 10(-8) M at 40 min and
      exhibited a t1/2 of 24 min. Based on its half-life, DT388-GM-CSF concentrations
      in the plasma are above the concentration inhibiting 50% protein synthesis and
      inducing apoptosis in 50% of HL-60 cells (AML cell line) for 5.2 h. Only four of
      17 mice developed a weak immune response (0.9-160 ng/mL) 3 weeks after treatment.
      DT388-GM-CSF exhibits a short t1/2, but concentrations exceed those required in
      vitro to inhibit AML cell lines.

PMID- 9630458
TI  - Elevations of intracellular Ca2+ as a probable contributor to decreased viability
      in cerebellar granule cells following acute exposure to methylmercury.
AB  - In these experiments we examined whether the elevations in intracellular Ca2+
      concentration ([Ca2+]i) induced by methylmercury (MeHg)(described in our previous
      study) might contribute to cerebellar granule cell mortality following exposure
      to MeHg in vitro. Cells were exposed to 0.5 microM MeHg for 45 min or 1 microM
      MeHg for 38 min, conditions previously shown to induce elevations in [Ca2+]i in
      these cells. Control cells were exposed to buffer alone for 60 min. Viability was
      assessed using the Live/Dead viability/cytotoxicity kit. At 30 min post-MeHg
      exposure, there was no immediate increase in cell mortality; however, by 3.5 h
      after the onset of MeHg exposure, cell viability decreased to 74 and 54% of
      control values for 0.5 and 1.0 microM MeHg, respectively. At 24.5 h after MeHg
      exposure, cell viability declined to approximately 27%. Losses in cell viability
      at 3.5 h were prevented by pretreating the granule cells for 65 min with the Ca2+
      chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
      tetrakis(acetoxymethyl)ester (BAPTA; 10 microM), then exposing the cells to MeHg
      in the continued presence of BAPTA; however, at 24.5 h, BAPTA no longer prevented
      MeHg-induced cell death. Exposure to the Ca2+ channel blockers omega-conotoxin
      MVIIC (1 microM) or nifedipine (1 microM), previously shown to delay elevations
      in [Ca2+]i with MeHg exposure in vitro, protected granule cells from MeHg-induced
      mortality at 3.5 h postexposure. These data suggest that at early time points,
      MeHg-induced increases in [Ca2+]i may contribute to granule cell mortality;
      however, the role of Ca2+ at later time points is unclear.

PMID- 9630459
TI  - 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces hepatic cytochrome P450
      dependent arachidonic acid epoxygenation in diverse avian orders: regioisomer
      selectivity and immunochemical comparison of the TCDD-induced P450s to CYP1A4 and
      1A5.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) markedly induced cytochrome P450 (CYP)
      dependent arachidonic acid metabolism in liver microsomes from hatchlings of four
      avian species belonging to four different orders: chick, pigeon, cormorant, and
      great blue heron, increasing formation of arachidonic acid epoxides (EETs),
      monohydroxyeicosatetraenoic acids (HETEs), omega-1, and omega-2 OH arachidonic
      acid products by fivefold or more. Microsomes from TCDD-induced hatchling chicks
      had the highest activity and the least restricted EET regioselectivity. omega-OH
      arachidonic acid, the principal constitutive metabolite in chick and pigeon liver
      microsomes and a major product for cormorant and great blue heron was not induced
      by TCDD. Constitutive EET formation in avian liver microsomes was very low except
      in cormorant microsomes where 8,9-EET was generated almost exclusively. Western
      blots of liver microsomes using polyclonal antisera to chick embryo-derived
      CYP1A4 and 1A5 recognized two TCDD-induced bands in each of the species. The
      chick bands had the same molecular weights as CYP1A4 and 1A5 (55 and 55.5 kDa,
      respectively) but those of the other species differed. Immunopurified antiserum
      monospecific for CYP1A5 recognized a band in microsomes from all of the avian
      species, and monospecific antiserum for CYP1A4 recognized a band in microsomes
      from chick, pigeon, and great blue heron. AntiCYP1A4 and 1A5 IgG immunoinhibited
      TCDD-induced mixed function oxidase activity completely in chick and chick embryo
      microsomes and only partially in the other avian microsomes. The results
      demonstrate that (1) TCDD causes much greater induction of CYP-dependent
      arachidonic acid metabolism, and of arachidonic acid epoxygenation in particular,
      in avian than in mammalian species; (2) TCDD induces two CYP1A-related enzymes in
      birds as in mammals; (3) CYP1A enzymes in the birds other than chicks are not
      identical to CYP1A4 and 1A5 but share some enzymatic and immunochemical
      characteristics with them; (4) constitutive omega-OH arachidonic acid in all of
      the avian species and 8,9-EET in cormorant are formed by CYP enzymes unrelated to
      CYP1A; and (5) two distinct characteristics of avian CYP1A enzymes are the
      acquisition by avian CYP1A4-related P450 of unique epitope(s) and by CYP1A5
      related P450 of unusual catalytic effectiveness for arachidonic acid
      epoxygenation.

PMID- 9630460
TI  - Characterization of phenotypic alterations induced by 2,3,7,8-tetrachlorodibenzo
      p-dioxin on thymocytes in vivo and its effect on apoptosis.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a highly toxic environmental
      pollutant and is well known for inducing thymic atrophy in mice, although the
      exact mechanism of its action remains unclear. Recent studies from our laboratory
      demonstrated that TCDD induces apoptosis in thymocytes and that Fas- mice
      (lpr/lpr) were more resistant to TCDD-induced immunotoxicity when compared to the
      Fas+ wild-type mice. Inasmuch as induction of apoptosis is associated with
      alterations in adhesion molecule expression, in the current study we analyzed the
      expression of a variety of surface molecules on thymocytes treated with TCDD in
      vivo. Interestingly, in thymocytes from mice treated with a single dose of 50
      micrograms/kg body wt of TCDD, there was a significant increase in the density of
      expression of CD3, alpha beta TCR, CD44, and IL-2R, and a decrease in the
      expression of J11d, CD4, and CD8 molecules when compared to the control
      thymocytes. These alterations were first visible 3 days after TCDD treatment and
      increased on Days 5 and 10 posttreatment. Furthermore, most of the alterations in
      the density of expression of various markers were dose dependent with minimal but
      significant changes at 0.1 microgram and maximum alterations at 50 micrograms/kg
      body wt of TCDD. At most lower concentrations (0.1-5 micrograms/kg), TCDD caused
      alterations in the density of cell surface markers but not in the percentage of
      cells expressing a specific molecule. It is striking that the phenotypic
      alterations were similar to those seen in normal thymocytes undergoing
      spontaneous apoptosis in vitro as previously reported. Together, the current
      study suggests that TCDD treatment induces phenotypic changes in thymocytes that
      are similar to those seen in normal thymocytes undergoing apoptosis. Also,
      because detection of apoptosis in vivo is difficult, phenotypic alterations in
      the density of thymocyte surface molecules may serve as a useful biomarker for
      toxicity involving apoptosis.

PMID- 9630461
TI  - The effect of a low-protein diet and dietary supplementation of threonine on
      tyrosine and 2-(2-nitro-4-trifluoromethylbenzoyl) cyclohexane-1,3-dione-induced
      corneal lesions, the extent of tyrosinemia, and the activity of enzymes involved
      in tyrosine catabolism in the rat.
AB  - Rats fed a low-protein diet and administered 2-(2-nitro-4
      trifluoromethylbenzoyl)cyclohexane-1,3-dione (NTBC) orally at 30 mumol/kg/day (10
      mg/kg/day) or fed a low-protein diet containing 5 ppm NTBC develop lesions to the
      cornea of the eye within 3-8 days of exposure with an incidence of about 80%.
      This treatment also produces a marked inhibition of both hepatic and renal 4
      hydroxyphenylpyruvate dioxygenase (HPPD) activity, an induction of hepatic but
      not renal tyrosine amino transferase activity, and a marked tyrosinemia in the
      plasma and aqueous humor. The extent of tyrosinemia and changes in the activity
      of tyrosine catabolic enzymes are similar to those reported for rats fed a normal
      protein diet and administered NTBC orally at 30 mumol/kg/day. However, the onset
      of corneal lesions occurs much earlier in rats fed a low-protein diet. The
      adverse ocular effects of NTBC can be alleviated by supplementing the low-protein
      diet with 1% w/w threonine. The protection afforded by threonine inclusion in the
      diet was not due to any amelioration in the extent of inhibition of hepatic HPPD
      activity or reduction in the extent of the tyrosinemia as measured 8 days after
      treatment. Rats fed L-tyrosine at 5% w/w in a low-protein diet rapidly develop
      lesions to the cornea of the eye, which are associated with a marked tyrosinemia,
      increased hepatic tyrosine aminotransferase activity, and about a 50% reduction
      in the activity of hepatic HPPD. The onset of corneal lesions produced by feeding
      a high tyrosine diet could be delayed, but not prevented, by inclusion of 1% w/w
      threonine in the low-protein diet. The basis for the beneficial effect of dietary
      supplementation of threonine in alleviating the corneal lesions produced by NTBC
      is unclear. However, our findings do illustrate that protein deficiency limits
      the ability of the rat to respond to a tyrosine load produced by inhibition of
      HPPD.

PMID- 9630462
TI  - A CFD-PBPK hybrid model for simulating gas and vapor uptake in the rat nose.
AB  - In laboratory studies of rodents, the inhalation of organic vapors often results
      in preferential damage to olfactory epithelium. Such focal lesion formation may
      be due either wholly or in part to a corresponding nonuniformity in the spatial
      distribution of vapor uptake within the nasal cavities. As a tool for determining
      this dose distribution, a mathematical model based on a combination of
      computational fluid dynamics (CFD) and physiologically based pharmacokinetic
      (PBPK) modeling was developed for simulating toxicant vapor uptake in the rat
      nose. The nasal airways were subdivided into four distinct meatuses selected such
      that each contained a major air flow stream. Each meatus was further divided into
      four serial regions attached to separate tissue stacks containing mucus,
      epithelial, and subepithelial compartments. Values for the gas-phase mass
      transfer coefficients and gas flows in the 16 airway regions were determined by a
      solution of the Navier-Stokes and convection-diffusion equations using
      commercially available CFD software. These values were then input to a PBPK
      simulation of toxicant transport through the 16 tissue stacks. The model was
      validated by using overall uptake data from rodent inhalation studies for three
      "unreactive" vapors that were either completely inert (i.e., acetone), reversibly
      ionized in aqueous media (i.e., acrylic acid), or prevented from being
      metabolized by an enzyme inhibitor (i.e., isoamyl alcohol). A sensitivity
      analysis revealed that accurate values of the mass transfer coefficient were not
      necessary to simulate regional concentrations and uptake of unreactive vapors in
      the rat nose, but reliable estimates of diffusion coefficients in tissue were
      crucial for accurate simulations.

PMID- 9630463
TI  - The absorption, blood levels, and excretion of mercury after a single dose of
      mercury vapor in humans.
AB  - Nine healthy volunteers without amalgam fillings were exposed to 400
      micrograms/m3 mercury vapor (Hg0) for 15 min, corresponding to 5.5 nmol Hg0/kg
      body wt (median range: 4.4-7.2). Frequent sampling of blood, urine, and exhaled
      air was performed for 30 days after exposure. The median retention of Hg0 was 69%
      of the inhaled dose. During the first 3 days after exposure 7.5-12% of the
      absorbed dose was lost by exhalation, with the median half time of Hg0 in expired
      breath being 2.0 days. In blood and plasma, a rapid absorption phase of Hg was
      seen, followed by a biexponential decline of the curves in both media. A
      substantial interindividual variation was observed in the area under the
      concentration-time curves of Hg in blood and plasma. In plasma the median half
      time of the second phase was 10 days. About 1.0% of the absorbed Hg was excreted
      via urine during the first 3 days after exposure, whereas the estimated amount
      excreted during 30 days ranged from 8 to 40%. In order to evaluate the chronic
      exposure to mercury from dental amalgam in the general population, the daily Hg
      dose from the fillings were estimated based on the plasma Hg levels found in
      subjects with amalgam fillings and on the plasma Hg clearance obtained in the
      present study. The daily Hg dose was estimated to 5-9 micrograms/day in subjects
      with an ordinary number of amalgam fillings.

PMID- 9630464
TI  - Reversal of hydroquinone-mediated suppression of T cell proliferation by
      transfection of the M2 subunit of ribonucleotide reductase.
AB  - Hydroquinone (HQ) is a benzene derivative that is found in large quantities in
      cigarette tar as a result of the pyrolysis of tobacco flavinoids. HQ is a potent
      inhibitor of T cell proliferation, causing an immediate and complete cessation of
      DNA synthesis in IL-2-dependent human T lymphoblasts and Jurkat T cells without
      loss of cell viability. Previous studies from our laboratory demonstrated that
      the antiproliferative effects of RQ could be partially reversed by the addition
      of deoxyribonucleosides, but not by the corresponding ribonucleosides, suggesting
      that HQ might inhibit ribonucleotide reductase. In the present study, the
      molecular mechanism behind this observation was further investigated. Jurkat T
      cells were stably transfected with a pMEP4 expression vector containing the gene
      for the M2 subunit of ribonucleotide reductase under transcriptional control of
      the human metallothionein IIA promoter. M2-transfected Jurkat T cells exhibited a
      greater than three-fold increase in resistance to HQ compared to untransfected
      cells or cells transfected with the M2 gene in the reverse orientation. HQ
      resistance was associated with an increased level of M2 protein detected by
      Western blot. These results suggest that the benzene derivative inhibits
      lymphocyte proliferation by inhibiting ribonucleotide reductase.

PMID- 9630465
TI  - Effect of cytochrome P450 inducers on cocaine-mediated hepatotoxicity.
AB  - The effect of several cytochrome P450 (P450) inducers on cocaine metabolism were
      examined in order to characterize the metabolic events contributing to cocaine
      induced hepatotoxicity. Phenobarbital (PB)-pretreatment of mice induced P450s 3A
      and 2B and markedly increased serum alanine aminotransferase (ALT) activity after
      cocaine or norcocaine administration. Although dexamethasone (Dex) induced P450s
      3A and 2B at least to the same extent as PB, no increase in serum ALT activity
      was observed after cocaine or norcocaine administration. Phencyclidine (PCP)
      pretreatment did not increase either P450s 3A or 2B, yet it markedly enhanced
      cocaine- or norcocaine-induced serum ALT activity. In contrast to the marked
      induction of P450s 3A and 2B, P450 2C was increased only 2.5-fold by PB and to an
      even lesser extent by Dex or PCP. Cannabidiol (CBD), which inactivates P450s 3A
      and 2C in mice, completely protected mice against cocaine- or norcocaine-induced
      hepatotoxicity irrespective of whether they were induced or not with PB or PCP.
      Both PB and Dex pretreatment increased the in vitro hepatic microsomal formation
      of the first two sequential oxidative metabolites of cocaine (norcocaine and N
      hydroxynorcocaine), whereas PCP pretreatment did not. Hepatic esterase activity
      was also determined after pretreatment with P450 inducers, since this is the
      major detoxification pathway in cocaine metabolism. Dex pretreatment markedly
      increased (> 11-fold) total hepatic esterase activity, whereas PB pretreatment
      increased it more modestly (less than fourfold) and PCP pretreatment had little
      effect. This marked effect of Dex pretreatment may decrease liver cocaine
      concentrations and thus protect mice against cocaine-induced hepatotoxicity,
      despite their increased P450 2B and 3A contents.

PMID- 9630466
TI  - Epoxybutene-hemoglobin adducts in rats and mice: dose response for formation and
      persistence during and following long-term low-level exposure to butadiene.
AB  - Measurement of specific adducts to hemoglobin can be used to establish the
      dosimetry of electrophilic compounds and metabolites in experimental animals and
      in humans. The purpose of this study was to investigate the dose response for
      adduct formation and persistence in rats and mice during long-term low-level
      exposure to butadiene by inhalation. Adducts of 3,4-epoxy-1-butene, the primary
      metabolite of butadiene, with N-terminal valine in hemoglobin were determined in
      male B6C3F1 mice and male Sprague-Dawley rats following exposure to 0, 2, 10, or
      100 ppm of 1,3-butadiene, 6 h/day, 5 days/week for 1, 2, 3, or 4 weeks. Blood
      samples were collected from groups of five mice and three rats at the end of each
      week during the 4 weeks of exposure and weekly for 3 weeks following the end of
      the 4-week exposure period. The increase and decrease, respectively, of the
      adduct levels during and following the end of the 4-week exposure followed
      closely the theoretical curve for adduct accumulation and removal for rats and
      mice, thereby demonstrating that the adducts are chemically stable in vivo and
      that the elimination follows the turnover of the red blood cells. The adduct
      level increased linearly with butadiene exposure concentration in the mice,
      whereas a deviation from linearity was observed in the rats. For example, after
      exposure to 100 ppm butadiene, the epoxybutene-hemoglobin adduct levels were
      about four times higher in mice than in rats; at lower concentrations of
      butadiene, the species difference was less pronounced. Blood concentrations of
      epoxybutene, estimated from hemoglobin adduct levels, were in general agreement
      with reported concentrations in mice and rats exposed by inhalation to 62.5 ppm.
      These studies show that adducts of epoxybutene with N-terminal valine in
      hemoglobin can be used to predict blood concentration of epoxybutene in
      experimental animals.

PMID- 9630467
TI  - Low-level lead exposure selectively enhances dopamine overflow in nucleus
      accumbens: an in vivo electrochemistry time course assessment.
AB  - Exposures to even very low levels of lead (Pb) alter behavioral and neurochemical
      functions. The current study was based on the hypothesis that excess synaptic
      dopamine (DA) availability may contribute to such disturbances and that the
      mesolimbic DA projection is more sensitive than the nigrostriatal system to Pb
      induced DA-based alterations. In vivo electrochemical measurements of potassium
      chloride-evoked DA overflow and clearance were compared in dorsal striatum (STR)
      (nigrostriatal system) and nucleus accumbens (NAC)(mesolimbic system) of male
      rats after 11 weeks or 11 months of postweaning exposure to 0, 50, or 150 ppm Pb
      acetate drinking solutions. Pb increased evoked DA overflow selectively in NAC,
      with biphasic effects at 11 weeks, including increases greater than 400% at 50
      ppm and concentration-related effects up to 265% of control at 11 months.
      Considered relative to 11-week control levels, continued exposure tended to
      attenuate the magnitude of Pb-related increases in DA overflow in NAC. Pb
      decreased clearance time in both brain regions, with these effects markedly
      augmented across time. These changes in DA function were observed at blood Pb
      values of only 15-16 micrograms/dl, underscoring their environmental relevance.
      The current findings support the hypothesis of excess DA availability as a
      mechanism of Pb-induced behavioral alterations and of a particular vulnerability
      of mesolimbic DA systems (NAC) to such effects. They also suggest that different
      mechanisms underlie Pb-related changes in amplitude and clearance and confirm
      previous reports of regional differences of DA systems in response to Pb
      exposure.

PMID- 9630468
TI  - Molecular dissection of dimethylnitrosamine (DMN)-induced hepatotoxicity by mRNA
      differential display.
AB  - Differential display reverse transcription-polymerase chain reaction (DDRT-PCR)
      was used to catalogue altered hepatic transcript expression during
      dimethylnitrosamine (DMN) exposure in vivo. Mice were administered DMN (1.5 or 5
      mg/kg) or vehicle (phosphate-buffered saline) i.p. once daily for up to 7 days,
      and livers were collected 6 h post-injection. Total RNA was reverse transcribed
      and cDNA subsets were selectively amplified by PCR. DDRT-PCR products were
      fractionated on denaturing polyacrylamide gels, and differentially expressed
      bands were excised, reamplified, and subsequently cloned into a plasmid vector.
      This study identified 23 cDNAs that were induced and 25 cDNAs that were
      suppressed during DMN exposure. Altered expression during DMN exposure for cDNA
      clones was confirmed by Northern blotting, RNase protection, or in situ
      hybridization analyses. DNA sequence information indicated that four cDNAs
      suppressed during DMN exposure encode cytochrome P450 isoenzyme-cholesterol 7
      alpha-hydroxylase (CYP7), a monokine, a myeloid cell differentiation protein, and
      mouse major urinary protein (MUP). We further observed a DMN-induced increase in
      transcripts for complement factor 3 (C3) and serum amyloid A (SAA). In contrast,
      the remaining differentially expressed transcripts detected by DDRT-PCR during
      DMN exposure demonstrated no similarity to sequences present in Genbank,
      suggesting that they may encode previously unreported gene products. In situ
      hybridization showed MUP transcripts to be expressed by hepatic centrilobular
      areas that undergo necrosis during subchronic DMN exposure. Thus, the utilization
      of DDRT-PCR has identified several differentially expressed hepatic mRNAs
      associated with various doses and stages of DMN exposure.

PMID- 9630469
TI  - Initial levels of azoxymethane-induced DNA methyl adducts are not predictive of
      tumor susceptibility in inbred mice.
AB  - Inbred mice vary in susceptibility to colon carcinogens such as 1,2
      dimethylhydrazine (DMH). Differential susceptibility may depend, in part, on
      formation of promutagenic DNA methyl adducts within target colonic mucosa. The
      present study was undertaken to evaluate the extent of DNA adduct formation in
      susceptible (SWR) and resistant (AKR) mice acutely exposed to the colon
      carcinogen azoxymethane (AOM), a direct metabolite of DMH. In the first
      experiment, 8-week-old SWR and AKR mice were treated i.p. with 20 mg/kg AOM and
      sacrificed 6 h later. DNA was isolated from distal colon and liver, and O6
      methylguanine (O6-MeGua) adduct levels were assessed by immunoslot blot (ISB)
      analysis, using a monospecific antibody raised against O6-methyldeoxyguanosine.
      HPLC-fluorescence detection was also used to quantitate 06-MeGua and 7
      methylguanine (7-MeGua), and to generate standard curves. At 6 h, both O6-MeGua
      and 7-MeGua were significantly higher (2- to 3-fold, p < 0.05) in AKR colon,
      while an opposite pattern was found in liver. In Experiment 2, mice were injected
      with AOM (20 mg/kg) and euthanized 12 and 48 h later. At 12 h, O6-MeGua levels
      were higher in colons (1.4-fold) of SWR mice. Forty-eight hours after treatment,
      however, adduct levels in colon were markedly (5-fold) reduced in SWR but were
      unchanged from 12 h in AKR. To further compare activation of AOM in both strains,
      colon microsomes were incubated with AOM and calf thymus DNA. Comparable levels
      of O6-MeGua were detected by ISB, demonstrating equivalent metabolic capacity in
      both SWR and AKR mice. These studies suggest that differential susceptibility to
      AOM-induced colon carcinogenesis is not based on initial target tissue DNA
      alkylation and unlikely to depend on differential metabolic capacity.

PMID- 9630470
TI  - Focal brain injury and its effects on cerebral mantle, neurons, and fiber tracks.
AB  - Following a mild cortical impact injury delivered by a piston to the right
      sensorimotor cortex of the anesthetized rat, we evaluated mantle loss, neuronal
      changes, and fiber track degeneration by deOlmos silver stains up to 8 weeks
      after injury. Darkened neurons indicating damage (chromatolysis) occurred widely
      throughout both hemispheres and were seen from 1 h to 8 weeks after injury. This
      effect might have occurred from pressure wave damage from piston impact, brain
      displacement or deafferentation. Cerebral mantle loss was variable but fiber
      track degeneration related to projection and corticofugal descending tracks
      associated with the right sensorimotor system was rather constant. Unexpectedly,
      considerable fiber track degeneration occurred within the cerebellum, especially
      the inferior vermis. Cells directly under the piston face were surprisingly well
      preserved but axon degeneration studies showed that these apparently intact
      neuronal cell bodies were surrounded by a dense network of degenerating fiber
      tracks. The intact cells, therefore, may have been functionally cut off from the
      rest of the brain owing to interruption of their efferents and afferents. The
      increased susceptibility of axons compared to cell bodies seen with this focal
      injury is similar to that observed with diffuse brain injury. The early
      appearing, severe and widespread axon damage we observed suggests that
      amelioration of focal traumatic brain injury will have to be directed promptly to
      the preservation of axons as well as cell bodies.

PMID- 9630471
TI  - GLUT4 glucose transporter expression in rodent brain: effect of diabetes.
AB  - This study describes the regional and cellular expression of the insulin
      sensitive glucose transporter, GLUT4, in rodent brain. A combination of in situ
      hybridization, immunohistochemistry and immunoblot techniques was employed to
      localize GLUT4 mRNA and protein to the granule cells of the olfactory bulb,
      dentate gyrus of the hippocampus and the cerebellum, with the greatest level of
      expression being in the cerebellum. Estimates of the concentration of GLUT4 in
      cerebellar membranes indicate that this transporter isoform is present in
      significant amounts, relative to the other isoforms, GLUT1 and GLUT3. Cerebellar
      GLUT4 expression was increased in the genetically diabetic, hyperinsulinemic,
      db/db mouse relative to the non-diabetic control, and even higher levels were
      observed in db/db female than db/db male mice. Levels of expression of GLUT4
      protein in cerebellum appear to respond to the level of circulating insulin, and
      are reduced in the hypoinsulinemic streptozotocin-diabetic rat. Exercise training
      also results in reduced insulin levels and comparably reduced levels of GLUT4 in
      the cerebellum. These studies demonstrate a chronic insulin-sensitive regulation
      of GLUT4 in rodent brain and raise the possibility of acute modulations of
      glucose uptake in these GLUT4 expressing cells.

PMID- 9630472
TI  - Adenoviral gene transfer to spinal-cord neurons: intrathecal vs. intraparenchymal
      administration.
AB  - The spinal cord is the site of many chronic, debilitating, neurological disorders
      that may be amenable to gene therapy. The present study, using quantitative and
      anatomical methods, examines the ability of replication deficient adenovirus to
      transfer a transcription cassette composed of the cytomegalovirus promoter
      driving the expression of the LacZ reporter gene (AdCMVbetagal) to spinal-cord
      neurons. Rats were microinjected with AdCMVbetagal into the spinal-cord
      parenchyma or subarachnoid space and sacrificed between 1 and 60 days post
      infusion. The spinal cord was assayed for beta-galactosidase (beta-gal) activity
      fluorometrically (MUG). Intraparenchymal injection resulted in significant beta
      gal activity at day 1, which peaked at day 7, and decreased at day 14 (21-, 57-
      and 9.8-fold of control respectively). The spatial distribution of beta-gal
      activity on day 7 was confined to the 1-cm section containing the injection site
      but was detected 2 cm caudal to this section by day 14. Histochemical staining
      and immunocytochemistry revealed a prominent reaction product in neurons,
      particularly motor neurons, and glia within the ventral grey matter bilaterally.
      Intrathecal viral injections showed comparatively modest, yet significant
      increases in beta-gal activity throughout the spinal cord with the greatest
      activity (170% control) closest to the catheter tip. This study demonstrates that
      AdCMVbetagal injected into the ventral spinal cord results in extensive in vivo
      neuronal gene transfer with beta-gal activity reaching a peak by day 7 and
      remaining detectable at 60 days. Intrathecal viral injections result in greater
      spatial distribution but a comparatively lower level of expression.

PMID- 9630473
TI  - Microglia-specific localisation of a novel calcium binding protein, Iba1.
AB  - Recently it has been shown that mRNA of Iba1 (ionized calcium binding adaptor
      molecule 1), which was a novel calcium binding protein cDNA-cloned by our group,
      is specifically expressed in microglia in cultures of rat brain cells [Imai et
      al. Biophys. Biochem. Res. Commun., 224 (1996) 855-862]. In the present study,
      immunocytochemical and immunohistochemical examinations demonstrated that Iba1
      protein is expressed in microglia alone both in cultured brain cells and in the
      brain, respectively. In a mixed cell culture of embryonic rat brain,
      immunocytochemically positive for Iba1 protein were the microglia but it was not
      detectable in neurons, astroglia, or oligodendroglia. Immunohistochemical
      staining of adult rat brain sections showed Iba1 protein to be specifically
      localised in ramified microglia. In addition, immunohistochemical staining and
      immunoblot analysis of activated microglia in the facial nucleus after facial
      nerve axotomy shows that expression of Iba1 protein was upregulated and peaked at
      7 days. These results indicated that localisation of Iba1 protein is restricted
      to microglia both in vitro and in vivo, and that Iba1 protein plays a role in
      regulating the function of microglia, especially in the activated microglia.

PMID- 9630474
TI  - Sequence, chromophore extraction and 3-D model of the photoactive yellow protein
      from Rhodobacter sphaeroides.
AB  - The photoactive yellow protein (pyp) gene has been isolated from Rhodobacter
      sphaeroides by probing with a homologous PCR-product. A sequence analysis shows
      that this pyp gene encodes a 124 AA protein with 48% identity to the three known
      PYPs. Downstream from pyp, a number of adjacent open reading frames were
      identified, including a gene encoding a CoA-ligase homologue (pCL). This latter
      protein is proposed to be involved in PYP chromophore activation, required for
      attachment to the apoprotein. We have demonstrated the presence of the
      chromophoric group, previously identified in PYP from Ectothiorhodospira
      halophila as trans 4-hydroxy cinnamic acid, in phototrophically cultured R.
      sphaeroides cells by capillary zone electrophoresis. The basic structure of the
      chromophore binding pocket in PYP has been conserved, as shown by a 3D model of
      R. sphaeroides PYP, constructed by homology-based molecular modelling. In
      addition, this model shows that R. sphaeroides PYP contains a characteristic,
      positively charged patch.

PMID- 9630475
TI  - Genotoxicity of the insecticide rotenone in cultured human lymphocytes.
AB  - We have investigated the genotoxic activity of rotenone on three genetic
      endpoints, sister-chromatid exchanges (SCE), chromosome aberrations (CA) and
      micronuclei (MN) in human lymphocyte cultures in the presence and absence of a
      metabolic activation system (S9 mix). Our results indicate that rotenone
      increases the frequency of binucleated micronucleated (BNMN) cells and causes a
      delay in the cell cycle but does not increase the frequency of CA and SCE at the
      concentrations used. The presence of S9 mix reduces the genotoxic activity of
      rotenone.

PMID- 9630476
TI  - NMR and luminescence studies on the formation of ternary adducts between HSA and
      Ln(III)-malonate complexes.
AB  - At physiological pH and in the presence of an excess of malonate ligand (MAL),
      the lanthanide ions (Ln=Eu(III), Gd(III) and Tb(III)) are under the form of
      [Ln(MAL)2(H2O)4]-. Upon addition of human serum albumin (HSA), formation of two
      different ternary adducts of stoichiometry HSA-Ln(MAL)x(H2O)q (x=2, q=2; x=2,
      q=4) is detected. On the basis of the reasonable assumption that the binding
      strength for the two sites on the protein are inversely proportional to the
      hydration state of the metal ion, stability constants of 4.0.103 M-1 and 3.5.102
      M-1 have been evaluated for the system with q=2 and q=4, respectively. Whereas
      for the stronger binding site it is suggested that the protein provides two or
      three donor atoms to the coordination cage of the Ln(III) ion, in the case of the
      weaker binding site it is likely that it corresponds to a simple electrostatic
      interaction between the negatively charged [Ln(MAL)2(H2O)4]- and positively
      charged groups on the surface of the protein.

PMID- 9630477
TI  - Ipsilateral turning behavior induced by unilateral microinjections of a
      cannabinoid into the rat subthalamic nucleus.
AB  - The subthalamic nucleus contains cannabinoid receptors and cannabinoid receptor
      mRNA. However, the role of cannabinoid receptors in this nucleus has not been
      examined. In order to investigate the functional role of cannabinoid receptors in
      the rat subthalamic nucleus, turning activity was observed following unilateral
      microinjection of the synthetic cannabinoid CP 55,940. CP 55,940 (10 microg)
      induced ipsilateral turning. This effect was blocked by coadministration of the
      cannabinoid receptor antagonist SR141716A (5 microg). These results suggest that
      cannabinoid receptors in the subthalamic nucleus mediate an inhibition of motor
      activity.

PMID- 9630478
TI  - Colon-specific genotoxicity of heterocyclic amines detected by the modified
      alkaline single cell gel electrophoresis assay of multiple mouse organs.
AB  - The in vivo genotoxicity of five heterocyclic amines-Trp-P-2 (13 mg/kg), IQ (13
      mg/kg), MeIQ (13 mg/kg), MeIQx (13 mg/kg), and PhIP (40 mg/kg)-in the mucosa of
      gastrointestinal and urinary tract organs (stomach, duodenum, jejunum, ileum,
      colon, and bladder) was studied by the alkaline single cell gel electrophoresis
      (SCG) (Comet) assay. Male CD-1 mice were sacrificed 1, 3, and 8 h after
      intraperitoneal injection. All the heterocyclic amines studied yielded
      statistically significant DNA damage in the colon but not the small intestine
      (duodenum, jejunum, and ileum) or urinary bladder. In this study, five
      heterocyclic amines were injected intraperitoneally to avoid the consequences of
      ingestion. Thus, the extensive damage to colon DNA was concluded to be due, at
      least in part, to a systemic effect.

PMID- 9630479
TI  - Characterization of desensitization in recombinant N-methyl-D-aspartate
      receptors: comparison with native receptors in cultured hippocampal neurons.
AB  - In the present study we have characterized the effect of Ca2+, glycine, and
      agonist concentration on inactivation and desensitization in native and
      recombinant N-methyl-d-aspartate (NMDA) receptors. In agreement with earlier
      studies on neurons, we found that in the presence of saturating glycine
      concentrations, lowering [Ca2+]o, will decrease inactivation of NMDA receptors in
      cultured hippocampal neurons. However, unlike native NMDA receptors under the
      same recording conditions, recombinant receptors did not exhibit Ca2+-dependent
      inactivation. We also show that the glycine-insensitive desensitization observed
      in the recombinant receptors is subunit dependent, as NR1a2A and NR1a2B receptors
      significantly desensitized while the NR1a2C combination did not. Furthermore, we
      show this form of desensitization in NR1a2A receptors is due to classic agonist
      induced desensitization. In addition, we demonstrate the presence of glycine
      dependent desensitization in recombinant receptors. The ability of glycine to
      inhibit desensitization correlates to the rank order of glycine's affinity for
      potentiating the peak response for each subtype. Finally, using ifenprodil in the
      presence of high and low glycine concentrations, we present evidence that both 2A
      like and 2B-like subtypes of receptors can independently coexist in single
      neurons.

PMID- 9630480
TI  - Escapable and inescapable stress differentially and selectively alter
      extracellular levels of 5-HT in the ventral hippocampus and dorsal periaqueductal
      gray of the rat.
AB  - The effects of escapable and yoked inescapable electric tailshocks on
      extracellular levels of serotonin (5-HT) in the ventral hippocampus and dorsal
      periaqueductal gray (dPAG) were measured by in vivo microdialysis. Inescapable,
      but not escapable shock increased extracellular 5-HT in the ventral hippocampus
      relative to restrained controls. Basal levels of 5-HT were elevated 24 h after
      inescapable shock, and previously inescapably shocked subjects exhibited an
      exaggerated 5-HT response to 2 brief footshocks. In contrast, escapable, but not
      inescapable shock, increased extracellular 5-HT in the dPAG, increased basal 5-HT
      in the dPAG 24 h later, and led to an enhanced 5-HT response to subsequent brief
      footshock.

PMID- 9630481
TI  - Neonatal alcohol exposure reduces NMDA induced Ca2+ signaling in developing
      cerebellar granule neurons.
AB  - Glutamatergic neurotransmission through NMDA receptors is critical for both
      neurogenesis and mature function of the central nervous system (CNS), and is
      thought to be one target for developmentally-induced damage by alcohol to brain
      function. In the current study we examined Ca2+ signaling linked to NMDA receptor
      activation as a potential site for alcohol's detrimental effects on the
      developing nervous system. We compared Ca2+ signals to NMDA in granule neurons
      cultured from cerebella of rat neonates exposed to alcohol (ethanol) during
      development with responses to NMDA recorded in separated control groups. Alcohol
      exposure was by the vapor chamber method on postnatal days 4-7. An intermittent
      exposure paradigm was used where the pups were exposed to alcohol vapor for 2. 5
      h/day to produce peak BALs of approximately 320 mg%. Control pups were placed in
      an alcohol-free chamber for a similar time period or remained with their mother.
      After culture under alcohol-free conditions for up to 9 days, Ca2+ signaling in
      response to NMDA was measured using fura-2 Ca2+ imaging. Results show that the
      peak amplitude of the Ca2+ signal to NMDA was significantly smaller in cultured
      granule neurons obtained from alcohol-treated pups compared to granule neurons
      from control pups. In contrast, the Ca2+ signal to K+ depolarization was not
      depressed by the alcohol treatment. Resting Ca2+ levels were also altered by the
      alcohol treatment. These results show that intermittent alcohol exposure during
      development in vivo can induce long-term changes in CNS neurons that affect the
      Ca2+ signaling pathway linked to NMDA receptors and resting Ca2+ levels. Such
      changes could play an important role in the CNS dysfunction associated with
      alcohol exposure during CNS development.

PMID- 9630482
TI  - Induction of sister chromatid exchanges and micronuclei by titanium dioxide in
      Chinese hamster ovary-K1 cells.
AB  - Titanium dioxide (TiO2) has color properties of extreme whiteness and brightness,
      is relatively inexpensive, and is extensively used as a white pigment in a
      variety of materials. TiO2, an effective blocker of ultraviolet light, is
      frequently added to sunscreens and cosmetic creams. However, the genotoxicity of
      TiO2 remains to be controversial. In this report, we have demonstrated that TiO2
      can be transported into Chinese hamster ovary-K1 (CHO-K1) cells. The effects of
      TiO2 on induction of sister chromatid exchanges (SCE) and micronuclei (MN) were
      then studied in these cells. The SCE frequency in CHO-K1 cells treated with TiO2
      at a nonlethal dose range (0 to 5 microM) for 24 h was significantly and dose
      dependently increased. By the conventional MN assay, TiO2 at the dose ranged from
      0 to 20 microM slightly increased the MN frequency in CHO-K1 cells. However, in
      the cytokinesis-block MN assay, the number of MN per 1000 binucleated cells was
      significantly and dose-dependently enhanced in CHO-K1 cells treated TiO2 at the
      same dose range for 24 h. These results suggest that TiO2 is a potential
      genotoxic agent.

PMID- 9630484
TI  - Construction of a human BcgI DNA fragment library.
AB  - A library made up of 36bp DNA fragments generated by digestion of human DNA with
      the restriction endonuclease Bcg I has been constructed. It contains 2.5x106
      independent clones, representing several times the total human genome which
      should contain about 400000 such fragments. It is proposed to make use of these
      BcgI fragments to clone part of the coding sequences contained in the minor H3
      isochore which represents 3% of the human genomic DNA and a quarter of all genes.

PMID- 9630483
TI  - Antibodies specific for (6-4) DNA photoproducts: cloning, antibody modeling and
      construction of a single-chain Fv derivative.
AB  - We have investigated a series of four monoclonal antibodies that specifically
      recognize pyrimidine (6-4) pyrimidone photoproducts. One of these antibodies
      (64M4), bound all four possible pyrimidine-pyrimidone photoadducts with equal
      affinities whereas the others (64M2, 64M3 and 64M5) were selective for TC and TT
      sequences. In addition, 64M5 had the highest binding affinity for photodamaged
      DNA of the four [T. Mori et al., Photochem. Photobiol. 54 (1991) 225-232]. To
      help understand the differences between these antibodies, we have cloned and
      sequenced the variable region genes from all four. Comparing these sequences
      revealed that all four were highly similar to one another, although there were
      some differences in potential antigen-contact regions. To assess the influences
      of these sequence differences at the structural level, computer models were
      constructed for all four antibodies. Most of the sequence differences occurred in
      potential antigen contact regions, suggesting specific positions that might
      account for the observed differences in binding affinities and selectivities. A
      single-chain Fv derivative of 64M5 was therefore constructed and characterized to
      provide an experimental system in which structure-function relationships can be
      tested. This derivative could be isolated from Escherichia coli using two
      chromatographic steps and possessed the same binding specificity as the parent
      monoclonal antibody.

PMID- 9630485
TI  - Sensitization of the nervous system, induced by two successive hindpaw
      inflammations, is suppressed by a local anesthetic.
AB  - Two hindpaw injections of carrageenin were performed 7 days apart and the time
      course of the vocalization thresholds to pressure (VTPP) of all the 4 paws of the
      rat were measured after both injections. The first injection of carrageenin
      induced an increase in the circumference of the injected paw and a significant
      reduction of the VTPPs of all the 4 paws. The pain-related behavior of both
      hindpaws was enhanced, when carrageenin was injected for the second time not only
      into the previously inflamed, but also into the contralateral hindpaw. However,
      the abnormal responses of the forepaws were not increased by this second hindpaw
      inflammation. Both after the first and the second injection of carrageenin, the
      decrease of the VTPPs of all 4 paws was antagonized by lidocaine with epinephrine
      (LE) injected into the inflamed paw. This anesthetic effect was of a shorter
      duration after the second than after the first injection of carrageenin.
      Presumably, the imprint that is left in the nervous system after the first
      hindpaw inflammation, takes place at a relatively limited segmental level. In
      addition, it is possible to influence the established sensitization of the
      nervous system by treating the peripheral process itself, even when the first
      injury has primed the nervous system to the second injury. However, there still
      seems to exist some excitatory influences that cannot be suppressed by the local
      anesthetic.

PMID- 9630486
TI  - Characterization of the mouse neurofilament light (NF-L) gene promoter by in
      vitro transcription.
AB  - We have used in vitro transcription to access the basic sequences and factors
      required for the transcription of the mouse neurofilament light promoter (pNF-L)
      in the absence of chromatin structure. Deletion from -1.7 to -154 results in
      little change in NF-L promoter activity using nuclear extracts from either brain
      (expressing) or liver (non-expressing) tissues. Further deletion to -29 results
      in a gradual five-fold drop in promoter activity in both extracts. Only
      replacement of the entire -148 to -29 region results in a drop in NF-L promoter
      activity to basal levels. Thus, the NF-L promoter differs from the mouse NF heavy
      (NF-H) and mid-sized (NF-M) promoters in that no specific sequence within the
      immediate upstream NF-L promoter region (-154 to -29) appears to be responsible
      for enhancement or brain-specific transcription. We show that the order of
      strength of the three NF promoters is NF-H>NF-M>NF-L and identify sequences that
      can increase or reduce transcription when placed in front of heterologous NF
      promoters. We conclude that the NF-L promoter is a modular, weak and promiscuous
      promoter whose regulation differs from NF-H or NF-M. Our data suggest that
      chromatin structure may play an important role in the regulation of the NF-L
      promoter.

PMID- 9630487
TI  - Serum mitogenic activity on in vitro glial cells in Neurofibromatosis type 1.
AB  - Glial mitogenic effect was investigated in sera from the following groups of
      subjects: group (1) 31 patients clinically and genetically affected by
      Neurofibromatosis type 1 (NF1) belonging to different families; group (2) 42
      patients without family history of NF1 affected by sporadic neoplasms of the same
      histogenetic origin as the proliferative lesions that are present in NF1; group
      (3) 51 healthy volunteers without family history of NF1 nor of neoplastic
      disease; group (4) 54 clinically healthy relatives of the NF1 patients included
      in the first group. All NF1 patients and 3/54 healthy relatives had alterations
      of exons 31 or 32 of NF1 gene. Glial proliferation, measured by [3H]thymidine
      incorporation, was significantly increased by sera from all NF1 patients and from
      23/54 of clinically healthy relatives, as compared to sera from healthy
      volunteers. This serum mitogenic activity strongly suggests the existence of
      soluble glial proliferating molecules in NF1 families. The molecular weight (3-30
      kDa), the heat- and freeze-stability and the specificity for glial cells, suggest
      that the molecules responsible for this mitogenic effect are different from the
      growth factors previously described in NF1-associated tumor extracts and from
      lymphokines. Within each NF1 family, the maximal serum dilution stimulating glial
      proliferation was similar both in affected members and in their clinically
      healthy relatives. Since none of the clinically healthy relatives showing serum
      mitogenic activity was positive for the NF1 mutation analysis and, conversely,
      those having altered exons 31 or 32 of NF1 gene did not show any mitogenic
      activity; these results suggest that the phenotype expression of NF1 might depend
      not only on the NF1 mutations per se, but also on other genetic or epigenetic
      factors, such as serum glial proliferating molecules.

PMID- 9630488
TI  - Comparative studies of DNA adduct formation in mice following dermal application
      of smoke condensates from cigarettes that burn or primarily heat tobacco.
AB  - A new cigarette (Eclipse) that primarily heats rather than burns tobacco has been
      developed. Since Eclipse primarily heats tobacco, the smoke chemistry is much
      simplified, consisting of 80% glycerol and water. With the simplified smoke
      chemistry, it would be expected that toxicological activity would be reduced.
      Smoke and smoke condensate from Eclipse have consistently yielded markedly
      reduced mutagenicity and cytotoxicity in in vitro tests when compared to smoke
      and smoke condensate from the 1R4F Kentucky reference cigarette, which is
      representative of typical low 'tar' cigarettes sold in the U.S. today. The
      objective of the present study was to evaluate the potential of mainstream
      cigarette smoke condensate (CSC) of Eclipse to produce DNA adducts in lung, heart
      and skin tissue of dermally-exposed mice and to compare the results with those
      obtained with CSC from the 1R4F Kentucky reference cigarette. CSC from Eclipse or
      1R4F cigarettes was applied dermally to SENCAR mice three times a week for 30
      weeks. Amounts of CSC applied were 30, 60 or 120 mg 'tar' per animal per week.
      Tissues were collected after 1, 4, 14 and 29 weeks of CSC application. DNA
      adducts were analyzed in lung, heart and skin tissues using the 32P-postlabeling
      method with P1 nuclease modification. Distinct time and dose-dependent diagonal
      radioactive zones (DRZ) were observed in the DNA from lung, heart and skin
      tissues of animals treated with 1R4F CSC. The relative adduct labeling (RAL)
      values of lung, heart and skin DNA from reference CSC-treated animals were
      significantly greater (p<0.05) than those of the solvent control animals. No
      corresponding DRZs were observed at any dose from the DNA of animals treated with
      CSC from Eclipse or solvent control (acetone) and the RAL values observed
      following application of Eclipse were not increased relative to the solvent
      control. These results provide additional evidence that the smoke condensate from
      the Eclipse cigarette is markedly less genotoxic than smoke condensate from
      tobacco-burning cigarettes representative of those currently sold in the U.S.

PMID- 9630489
TI  - Delayed selective motor neuron death and fas antigen induction after spinal cord
      ischemia in rabbits.
AB  - The mechanism of spinal cord injury has been thought to be related with tissue
      ischemia, and spinal motor neuron cells are suggested to be vulnerable to
      ischemia. To evaluate the mechanism of such vulnerability of motor neurons, we
      attempted to make a reproducible model for spinal cord ischemia. Using this
      model, cell damage was histologically analyzed. Detection of ladders of
      oligonucleosomal DNA fragment was investigated with gel electrophoresis up to 7
      days of the reperfusion. Time course expression of Fas antigen, identified as a
      apoptosis-regulating molecules, was also assessed in rabbit spinal cord following
      transient ischemia. Spinal cord sections from animals sacrificed at 8 h, 1 day, 2
      days, and 7 days following 15-min ischemia were immunohistochemically evaluated
      using monoclonal antibodies for Fas antigen. Following 15-min ischemia, the
      majority of motor neuron showed selective cell death at 7 days of reperfusion.
      Typical ladders of oligonucleosomal DNA fragments were detected at 2 days of
      reperfusion. Immunoreactivity of Fas antigen were induced at 8 h to 1 day of
      reperfusion selectively in motor neuron cells. The expression of Fas antigen may
      be related to the activation of apoptosis signal in motor neuron cells after
      spinal cord ischemia in rabbits.

PMID- 9630490
TI  - Polymorphic insertions/deletions of both 1550nt and 100nt in two microsatellite
      containing, LINE-related intronic regions of the rabbit kappa-casein gene.
AB  - The most frequent allele of the rabbit kappa-casein (kappa-Cas)-encoding gene (A
      allele) has previously been shown to possess two sequences similar to those found
      in the 5' end of long interspersed repeated elements (LINE). Part of an inverted
      rabbit LINE is present in the first intron and part of a direct rabbit LINE in
      the fourth intron. We describe herewith a less frequent allele (B allele) that
      lacks both 100bp in the first intron and 1550bp in the fourth intron. It was not
      possible to identify any allele exhibiting only one of the deletions in a
      population of 55 rabbits. The 100bp present in the first intron of the A allele,
      but absent from the B allele, are located at the 5' end of the inverse
      complementary LINE and include the poly (T) track of the LINE. The 1550bp present
      in the fourth intron of the A allele, but absent from the B allele, include the
      entire direct LINE sequence. Therefore, the B allele only possesses one partial
      LINE sequence that is located in the first intron and is truncated when compared
      to the copy found in the first intron of the A allele. The B allele might thus be
      more recent than the A allele. Differences between the sequences of transcripts
      corresponding to each allele are limited to two silent mutations and three
      modifications in the 3' UTR. In the mammary glands of lactating rabbits, which
      are homozygous for both alleles, kappa-Cas mRNA accumulate to similar levels and
      are translated into identical kappa-Cas that are secreted at similar
      concentrations into milk.

PMID- 9630491
TI  - Flat and steep terminal negativity in the DC-potential after deprivation of
      oxygen and glucose in human neocortical slices.
AB  - The so-called terminal negativity (TN) of the DC-potential is a characteristic
      reaction of neuronal tissue to hypoxia or ischemia. In a previous study on human
      neocortical slices, two types of TN with flat and steep slopes of rise (< or >10
      mV/min) were found with hypoxia. The aim of the present study was to further
      investigate causes underlying the occurrence of flat and steep TN. Experiments
      were performed on 23 human neocortical slices (500 micron) resected from 13
      patients (epilepsy and tumour surgery). DC-potential and evoked potentials (white
      matter stimulation) were recorded in layer III. The extracellular potassium
      concentration ([K+]o) was measured by K+-sensitive microelectrodes. In an
      interface type chamber, ischemic episodes were induced by oxygen and glucose
      deprivation. They were terminated when TN had peaked. Both flat and steep TN also
      existed with ischemic conditions. There was a linear correlation between the
      slope of rise of TN and the associated slope of rise in [K+]o, respectively, but
      none regarding latencies of TN or recovery of evoked potentials. Peak levels in
      [K+]o were 13.9+/-0.9 mmol/l. Compared to control, the slope of rise and latency
      of TN were clearly increased by addition of dimethyl sulfoxide (DMSO, 0.4%) to
      the bath solution, whereas nimodipine (40 micromol/l) in 0.4% DMSO had neither an
      effect on slope of rise of TN nor on latency of TN. As a whole, our observations
      suggest, that the actual metabolic state determines the occurrence of flat or
      steep TN.

PMID- 9630492
TI  - Changing patterns of brain activation during maze learning.
AB  - Recent research has found that patterns of brain activation involving the frontal
      cortex during novel task performance change dramatically following practice and
      repeat performance. Evidence for differential left vs. right frontal lobe
      activation, respectively, during episodic memory encoding and retrieval has also
      been reported. To examine these potentially related issues regional cerebral
      blood flow (rCBF) was measured in 15 normal volunteers using positron emission
      tomography (PET) during the naive and practiced performance of a maze task
      paradigm. SPM analysis indicated a largely right-sided, frontal lobe activation
      during naive performance. Following training and practice, performance of the
      same maze task elicited a more posterior pattern of rCBF activation involving
      posterior cingulate and precuneus. The change in the pattern of rCBF activation
      between novel and practiced task conditions agrees with results found in previous
      studies using repeat task methodology, and indicates that the neural circuitry
      required for encoding novel task information differs from that required when the
      same task has become familiar and information is being recalled. The right-sided
      preponderance of activation during naive performance may relate to task novelty
      and the spatially-based nature of the stimuli, whereas posterior areas activated
      during repeat performance are those previously found to be associated with
      visuospatial memory recall. Activation of these areas, however, does not agree
      with previously reported findings of left-sided activation during verbal episodic
      memory encoding and right-sided activation during retrieval, suggesting different
      neural substrates for verbal and visuospatial processing within memory.

PMID- 9630493
TI  - Transient amelioration of the sensitization of cocaine-induced behaviors in rats
      by the induction of tolerance.
AB  - Intermittent administration of cocaine produced a progressive increase in the
      stereotypy response of rats to a challenge dose of cocaine (7.5 mg/kg, i.p.).
      Continuous infusion of cocaine (80 mg/kg per day) via osmotic pumps for 7 days
      into the sensitized rats produced tolerance to the behavioral responses to the
      challenge dose of cocaine 1 day after the removal of the pumps. Therefore,
      tolerance can mask the expression of behavioral sensitization in rats. However,
      by 10 days after the removal of the pumps, the behavioral tolerance was reversed
      and the rats again displayed a sensitized response to cocaine. Therefore, the
      tolerance to cocaine was temporary while the underlying sensitization persisted.
      The development of tolerance did not alter the underlying sensitization
      demonstrating that these represent independent phenomena. The relationship
      between sensitization and tolerance observed in these studies may provide a model
      relevant to the progress in humans of addiction to psychomotor stimulants.

PMID- 9630495
TI  - No induction of chromosome aberrations in human spermatozoa exposed to extremely
      low frequency electromagnetic fields.
AB  - Clastogenic effects of extremely low frequency electromagnetic fields (ELF-EMFs)
      on human sperm chromosomes were studied using an interspecific in vitro
      fertilization system with zona-free golden hamster oocytes. Semen samples from
      healthy men were exposed to ELF-EMFs (50 Hz, 20 mT) for 2 h at 37 degreesC under
      5% CO2 in air. The samples were then cryopreserved in liquid nitrogen for
      shipment to a cytogenetic laboratory. After thawing the samples, motile
      spermatozoa were collected using a continuous Percoll density gradient
      centrifugation and then capacitated for in vitro fertilization with hamster
      oocytes. Sperm-derived chromosomes were analyzed at first cleavage metaphase. The
      present experiment was performed twice using semen samples from two different
      donors. In test-1, incidence of spermatozoa that displayed structural chromosome
      aberrations was 17.0% (35/206) in the exposed group and 20.8% (55/264) in the
      control group. In test-2, structural chromosome aberrations were observed in
      11.1% (13/117) of exposed spermatozoa and 13.8% (13/94) of spermatozoa in the
      control group. In both tests, there was no significant difference in the
      incidence of chromosomally abnormal spermatozoa between the exposed group and the
      control group. Types of aberrations observed and their incidences per
      spermatozoon in the exposed group were similar to those of the control group.
      Despite the small sample size, the present results suggest that ELF-EMFs have no
      clastogenic effect on human sperm chromosomes.

PMID- 9630494
TI  - Regulation of rat brain vesicular monoamine transporter by chronic treatment with
      ovarian hormones.
AB  - Ovarian steroids play an important role in neuroregulation and in the
      pathophysiology of various neuropsychiatric disorders. Most of the studies
      focused on the impact of gonadal steroids on post-synaptic receptors and plasma
      membrane transporters. In the present study, we evaluated the effect of chronic
      treatment with ovarian steroids on the expression of rat brain vesicular
      monoamine transporter (VMAT2). Ovariectomized rats were treated for 21 days with
      estradiol, progesterone or both. VMAT2 gene expression was assessed on the
      protein level by high affinity [3H]dihydrotetrabenazine ([3H]TBZOH) binding using
      autoradiography and on the mRNA level by in situ hybridization. Progesterone
      administration led to a decrease in [3H]TBZOH binding in the middle striatum and
      in the nucleus accumbens and to a parallel decrease in VMAT2 mRNA level in the
      substantia nigra pars compacta and dorsal raphe nuclei. Chronic estradiol
      treatment reduced VMAT2 mRNA level in the dorsal raphe and [3H]TBZOH binding in
      middle part of the striatum and nucleus accumbens but did not affect VMAT2 mRNA
      level in the substantia nigra pars compacta. Simultaneous administration of both
      ovarian steroids did not modulate VMAT2 mRNA in the substantia nigra pars
      compacta as well as [3H]TBZOH binding in the striatum or the nucleus accumbens
      but reduced VMAT2 mRNA level in the dorsal raphe. It appears that ovarian
      steroids may play a crucial role in the regulation of VMAT2 gene expression in
      the dopamine and serotonin systems. This modulatory activity may be relevant to
      synaptic and neuronal plasticity as well as to the molecular and cellular
      pathophysiology of gender-specific neuropsychiatric disorders.

PMID- 9630496
TI  - A splice site mutation gives rise to a mutant of the C4 plant Amaranthus edulis
      deficient in phosphoenolpyruvate carboxylase activity.
AB  - The molecular nature of a mutant of the C4 plant Amaranthus edulis that has been
      shown to contain only 5% of the normal activity and protein of
      phosphoenolpyruvate carboxylase (PEPC) (Dever et al., 1995) has been
      investigated. Using Northern blot analysis, it has been shown here that the PEPC
      transcripts are produced in the mutant. In-vitro translation of these transcripts
      generated two products immunoprecipitable by a PEPC N-terminus-specific antibody.
      One of these products has the size of the complete PEPC polypeptide, the other is
      9kDa smaller and was not revealed when using a PEPC C-terminus-specific antibody.
      In the mutant plant, using the same N- and C-terminus-specific antibodies, only
      the larger polypeptide was immunodetected, whilst at a very low level. A sequence
      analysis of the suspected faulty region of the mRNA revealed incorrect splicing
      of the last intron of the PEPC pre-mRNA. Two mis-splicings have been identified,
      both occurring after an AG site, one leading to a protein lacking five amino
      acids, the other to a truncated protein due to a stop codon generated by a frame
      shift in the translation. Finally, the sequencing of the boundary between the
      last intron and exon showed that these inaccurate splicings result from a
      mutation in the genuine canonical 3'AG splicing site.

PMID- 9630497
TI  - Role of the gamma chain Ala-Gly-Asp-Val and Aalpha chain Arg-Gly-Asp-Ser sites of
      fibrinogen in coaggregation of platelets and fibrinogen-coated beads.
AB  - Fibrinogen (Fg) mediates platelet aggregation and adhesion to artificial
      surfaces. The carboxyl terminus of the gamma chain of Fg (residues AGDV at
      gamma408-411) is known to play an exclusive role in platelet aggregation, while
      there is no known role for the consensus RGD sites in the Aalpha chain. In this
      study, we used flow cytometry to measure the coaggregation (CA) of platelets with
      Fg-coated beads, and investigated which domains in surface-immobilized Fg support
      platelet adhesion. CA of platelets with Fg-beads was nearly abolished in the
      presence of 4A5, a monoclonal antibody (mAb) whose epitope includes AGDV, while
      Z69/8, a mAb that also binds to the gamma chain carboxyl terminus but does not
      cover AGDV, had little effect. When beads were coated with recombinant Fg (rFg)
      lacking AGDV, CA was similarly abolished. In contrast, beads coated with Fg that
      lacked the RGDS site, supported platelet CA as did intact Fg. These results were
      confirmed in experiments that measured the binding of activated soluble
      glycoprotein IIb and IIIa (GPIIbIIIa), the platelet membrane glycoprotein complex
      known to be the Fg receptor, to immobilized Fg. This binding was inhibited by mAb
      4A5, but not by mAb Z69/8. Binding was totally retained when beads were coated
      with Fg lacking RGDS, but was completely lost when beads were coated with Fg
      lacking AGDV. These results demonstrated that the AGDV sequence on the carboxyl
      terminus of the gamma chain of Fg plays an exclusive role in platelet adhesion to
      surface-immobilized Fg, while the carboxyl terminus of the Aalpha chain,
      including a consensus RGD site, is not required.

PMID- 9630498
TI  - Monosynaptic activation of CA3 by the medial perforant path.
AB  - The functional projection of the medial perforant path (MPP) to different CA3
      subfields was studied in urethan-anesthetized rats using current source density
      analysis. MPP stimulation resulted in an early-latency (presumed monosynaptic)
      sink with onset of 2-3 ms at the distal apical dendritic layer of CA3 (stratum
      lacunosum molecule) and a long-latency (presumed disynaptic, >7 ms) sink at
      stratum lucidum and radiatum of CA3. The population spike (onset 5. 3-6.1 ms), a
      sink at CA3 pyramidal cell layer, was observed 67% of the time (12 of 18 rats) in
      CA3a, 44% (8 of 18) in CA3b and 58% (7 of 12 rats) in CA3c following MPP
      stimulation. Population spike was not observed during presumed disynaptic
      excitation of CA3. Both early-latency sink (excitatory postsynaptic potential)
      and population spike in CA3 revealed robust paired-pulse facilitation (PPF). In
      contrast, little PPF was found for the MPP-evoked excitatory sink at the middle
      molecular layer of the dentate gyrus. The data suggested that the entorhinal
      cortex provides a strong monosynaptic excitation of different subfields of CA3. A
      direct entorhinal to CA3 input bypasses the dentate gyrus and may play a role in
      normal hippocampal signal processing and neural plasticity.

PMID- 9630499
TI  - Enhanced sensitivity of the nucleus accumbens proenkephalin system to alcohol in
      rats selectively bred for alcohol preference.
AB  - Evidence suggests that alcohol-induced activation of the endogenous opioid system
      is part of a neurobiological mechanism that may be functionally involved in
      alcohol reinforcement and high alcohol drinking behavior. We postulate that a
      genetic predisposition toward alcohol drinking is accompanied by increased
      responsiveness of the opioid system to alcohol. To test this hypothesis, the
      present study compared the effect of an acute alcohol challenge on enkephalin
      gene expression in discrete brain regions which are high in preproenkephalin
      (PPENK) mRNA content and/or are important in mediating alcohol reward in rats
      selectively bred for alcohol preference (P) or nonpreference (NP). PPENK mRNA
      content was measured by in situ hybridization performed with a 36 base
      oligonucleotide probe for PPENK mRNA and was quantified using a computerized
      image-analysis system. Blood alcohol concentration (BAC) and rate of alcohol
      elimination following alcohol infusion were similar in P and NP rats. P and NP
      rats did not differ in basal content of PPENK mRNA in any of the brain areas
      examined prior to onset of infusion. An intragastric (I.G.) infusion of alcohol
      (2.5 g/kg b.wt) produced a significant increase in PPENK mRNA in the nucleus
      accumbens (both shell and core) of P but not NP rats at 1 h after the onset of
      infusion which coincided with the time at which peak BAC was attained. In
      contrast, at 8 h after the onset of the alcohol infusion, when BAC was falling
      toward baseline, PPENK mRNA was decreased in the nucleus accumbens of both P and
      NP rats and in the anterior striatum and amygdala of NP rats. The results suggest
      that enhanced responsiveness of the enkephalinergic system to alcohol is
      associated with, and may be functionally involved in, mediating high alcohol
      drinking behavior.

PMID- 9630500
TI  - Evaluation of auramine genotoxicity in primary rat and human hepatocytes and in
      the intact rat.
AB  - Auramine, a dye previously found to be a liver carcinogen in both mice and rats,
      was evaluated for its DNA-damaging and clastogenic activities in primary cultures
      of rats and human hepatocytes and for the induction of DNA single-strand breaks
      in the liver and urinary bladder mucosa of intact rats. A similar dose-dependent
      frequency of DNA fragmentation was revealed by the alkaline elution technique in
      metabolically competent primary cultures of both rat and human hepatocytes
      exposed for 20 h to subtoxic concentrations ranging from 10 to 32 microM. In
      contrast, neither rat nor human hepatocytes displayed an increased frequency of
      micronuclei after a 48-h exposure to the same auramine concentrations. In rats
      given a single oral dose of 125, 250 or 500 mg kg-1 auramine, the Comet assay
      revealed a significant increase in the frequency of DNA lesions in the liver and
      in the urinary bladder mucosa, the effect being slightly more marked in the
      liver. Taken as a whole and compared with previous findings, these results
      suggest that auramine is biotransformed into reactive species in target organs of
      both rats and humans, and that this dye might play by itself the main role in the
      increased incidence of bladder cancer which has been judged as causally related
      to its manufacture.

PMID- 9630501
TI  - A shuttle mutagenesis system for tagging genes in the yeast Yarrowia lipolytica.
AB  - A shuttle mutagenesis system was developed for the dimorphic yeast Yarrowia
      lipolytica. This system combines transposon insertions generated in Escherichia
      coli with the transformation of yeast with the Tn-mutagenized DNA. The mini
      transposon mTn-3xHA/GFP, used in Saccharomyces cerevisiae for producing stable
      insertions, was adapted for use in the yeast Y. lipolytica. The mTnYl1 transposon
      (for mini-Tn of Y. lipolytica) confers resistance to tetracycline in E. coli. It
      also contains the Y. lipolytica URA3 gene for selection of yeast transformants,
      and the coding sequence for the S65T mutant form of GFP. The rare cutter
      endonuclease, I-SceI, restriction site, which enables identification of the
      chromosomal localization of mutagenized genes, was also incorporated. mTnYl1 was
      first tested on the ACO1 gene, which encodes an Acyl CoA oxidase isozyme. The
      mutagenesis system was further validated on a Y. lipolytica genomic DNA library
      constructed in a pHSS6 derivative vector. Mutants with a particular morphology or
      defective for alkane, fatty acids and oil degradation were obtained.

PMID- 9630502
TI  - Differential regulation of FGF-2 and FGFR-1 in rat cortical astrocytes by
      dexamethasone and isoproterenol.
AB  - We have used rat cortical astrocytes in culture to investigate the signaling
      pathways involved in the regulation of fibroblast growth factor-2 (FGF-2) and one
      of its high affinity receptor FGF receptor-1 (FGFR-1). These cells represent a
      source of different neurotrophic factors and play important roles in
      physiological and pathological conditions of the central nervous system. FGF-2
      mRNA levels are increased by stimulation of beta-adrenergic receptors or exposure
      to glucocorticoid hormones and these effects are additive to each other. The
      regulation of FGFR-1, highly expressed in cultured astroglial cells, appears to
      be different. Isoproterenol produced an elevation of FGFR-1 mRNA levels, whereas
      dexamethasone decreased its expression alone or in the presence of isoproterenol,
      suggesting that the glucocorticoid pathway may predominate over the cAMP-induced
      up-regulation of the receptor. FGF-2 over-expression may produce different
      cellular responses depending on the concomitant regulation of its receptor and
      the cell phenotype where these changes do occur. These mechanisms can contribute
      to adaptive changes taking place in the CNS in different physiological and
      pathological situations.

PMID- 9630503
TI  - A novel AMPA receptor antagonist, YM872, reduces infarct size after middle
      cerebral artery occlusion in rats.
AB  - The neuroprotective effect of YM872 ([2.3-dioxo-7-(1H-imidazol-1-yl) 6-nitro
      1,2,3,4-tetrahydro-1-quinoxalinyl]acetic acid monohydrate), a novel alpha-amino-3
      hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor antagonist with improved
      water solubility, was examined in a rat focal cerebral ischemia model. Rats were
      subjected to permanent middle cerebral artery (MCA) occlusion using the
      intraluminal suture occlusion method for 24 h. YM872 was intravenously infused
      for 4 h (20 and 40 mg/kg/h) or 24 h (10 and 20 mg/kg/h), starting 5 min after the
      MCA occlusion, to investigate the effect of prolonged duration of the treatment
      on infarct volume. In the 4 h infusion study, YM872 reduced the cortical infarct
      volume by 48% at a dose of 40 mg/kg/h. YM872 did not significantly reduce the
      infarct at 20 mg/kg/h for 4 h. In the 24 h infusion study, however, YM872
      markedly reduced the cortical infarct volume by 62%, even at 20 mg/kg/h. The
      present study indicates that the neuroprotective effect of YM872 is enhanced by
      extending the duration of treatment, and demonstrates the benefit of the
      prolonged treatment with AMPA antagonists following focal cerebral ischemia.
      YM872, a highly water soluble compound, is applicable to investigate the role of
      AMPA receptors in ischemic models without concern about nephrotoxicity and could
      be useful in the treatment of human stroke.

PMID- 9630504
TI  - Normal and drug-induced locomotor behavior in aging: comparison to evoked DA
      release and tissue content in fischer 344 rats.
AB  - The consequences of aging on dopamine (DA) regulation within the nigrostriatal
      and mesolimbic systems were investigated with a combination of behavioral, in
      vivo electrochemical, and high-performance liquid chromatography measurements
      using 6-, 12-, 18- and 24-month old male Fischer 344 (F344) rats. Spontaneous
      locomotor testing demonstrated that aged (18- and 24-month) rats moved
      significantly less and at a slower speed than younger (6- and 12-month) animals.
      Additionally, systemic injection (intraperitoneal) of the DA uptake inhibitor,
      nomifensine, was significantly less efficacious in augmenting the locomotor
      activity of aged rats compared to the younger animals. Age-dependent alterations
      in the release capacity of DA neurons within the regions involved in movement
      were investigated using in vivo electrochemistry. These recordings indicated that
      both the magnitude and temporal dynamics of potassium (70 mM)-evoked DA overflow
      were affected by the aging process. Signal amplitudes recorded in the 24-month
      rats were 30-60% reduced in both the striatum and nucleus accumbens as compared
      to the young adult groups. In addition, the duration of the electrochemical DA
      signals recorded within the striatum of 24-month old rats was twice that in the
      younger animals (6- and 12-month). Whole tissue measurements of DA and DA
      metabolites suggest age-related deficits in locomotion and DA release were not
      related to decreases in the storage or synthesis of DA within the striatum,
      nucleus accumbens, substantia nigra, ventral tegmental area or medial prefrontal
      cortex. Taken together, these results indicate age-dependent deficits in movement
      are related to the dynamic properties of DA release and not static measures of DA
      content.

PMID- 9630505
TI  - Studies on the chymotrypsin-catalysed hydrolysis of resorufin acetate and
      resorufin bromoacetate.
AB  - Resorufin bromoacetate is a substrate that is rapidly hydrolysed by chymotrypsin.
      The reaction shows a pre-steady-state burst phase that may be observed by stopped
      flow spectrophotometry if precautions are taken against spontaneous hydrolysis of
      the substrate. The strongly activating effect that the presence of the bromine
      atom has on the adjacent carbonyl group is reflected in the relative sizes of the
      kcat values for resorufin bromoacetate and resorufin acetate (e.g., 740 to 1, at
      pH 6) and the burst rate constants (e.g., 350 to 1, at pH 7 using 0.1 mM
      substrate). The pH-dependence of kcat for both substrates shows the involvement
      of an enzymic group of pKa about 7. With resorufin bromoacetate, a burst and a
      steady-state rate are still observable at pH 3.0. Unlike the case with aldehyde
      dehydrogenase, resorufin bromoacetate does not act as an inactivator of
      chymotrypsin and there is little or no incorporation of covalently-linked label
      when chymotrypsin and resorufin bromoacetate are incubated together. The
      different modes of behaviour of the two enzymes are attributable to the 'hard' or
      'soft' character of the attacking enzymic nucleophilic groups.

PMID- 9630507
TI  - Molecular analysis of a novel protein kinase in maturing rice seed.
AB  - Protein kinases play important roles in controlling biological functions. We
      employed PCR-based cloning technique to isolate a protein kinase gene from rice
      endosperm and obtained a novel protein kinase (REK) cDNA clone from a cDNA
      library constructed from maturing rice seed. The deduced amino acid sequence from
      the cDNA exhibited a high similarity to the wheat abscisic acid inducible protein
      kinase (PKABA1), including 11 conserved regions of the catalytic domain. REK
      belongs to the SNF1-related family that possesses abundant acidic amino acid
      resides in the C-terminal region. RT-PCR analysis showed that the REK gene is
      expressed in leaf and maturing seed, but not in stem and root. Bacterial
      recombinant REK showed autophosphorylation activity depending upon Ca2+. In
      addition, we isolated a REK genomic clone and determined its gene structure.

PMID- 9630506
TI  - Regulation of immediate early gene c-fos and zif/268 mRNA expression in rat
      striatum by metabotropic glutamate receptor.
AB  - Metabotropic glutamate receptors are coupled to multiple intracellular second
      messenger systems through G-proteins and densely expressed by medium spiny
      projection neurons in the rat striatum. In chronically-cannulated rats, this
      study demonstrated that pharmacological activation of metabotropic glutamate
      receptors by intrastriatal injection of a selective agonist, ACPD, elevated
      immediate early gene c-fos and zif/268 mRNA expression in the injected dorsal
      striatum as revealed by quantitative in situ hybridization. The elevation of both
      c-fos and zif/268 was dose-dependent and the responsiveness of c-fos to ACPD at
      each dose surveyed was greater than that of zif/268. Induction of the two mRNAs
      was rapid and transient as increases in the 2 mRNAs became evident as early as 30
      min, reached a peak at 1 h, and returned to normal levels 3 (c-fos) or 6
      (zif/268) h, after ACPD injection. Coadministration of the selective metabotropic
      glutamate receptor antagonist, MCPG, with ACPD markedly attenuated ACPD
      stimulated c-fos, but not zif/268, expression. Pretreatment with the ionotropic
      NMDA receptor antagonist, CPP, had no effect on ACPD-stimulated c-fos expression,
      but partially attenuated ACPD-stimulated zif/268 expression. Blockade of D1
      dopamine receptors with SCH-23390 did not alter the ability of ACPD to induce the
      expression of these genes. These data demonstrate a difference between the
      profound induction of c-fos and zif/268 gene expression in response to specific
      activation of metabotropic glutamate receptors in striatal neurons. Furthermore,
      c-fos induction was independent of D1 dopaminergic and NMDA glutamatergic
      transmission, whereas zif/268 induction was mediated, at least in part, by NMDA
      receptors.

PMID- 9630508
TI  - A variant very low density lipoprotein receptor lacking 84 base pairs of O-linked
      sugar domain in the human brain myelin.
AB  - The very low density lipoprotein receptor (VLDLR) was considered to specifically
      bind to VLDL rich apolipoprotein E (apoE). However, its distribution and
      functions in vivo have yet to be elucidated. In human and rat VLDLR, a variant
      form lacking 84 base pairs (bp) in O-linked sugar domain was noted but its
      significance was not initially understood. This study shows that the variant form
      of VLDLR coexists with full-length VLDLR in majority of tissues but is a major
      component in the white matter of human brain. The tissue distribution of a
      variant VLDLR was detected in myelin as well as in other tissues except for the
      liver with immunohistochemistry using a monoclonal antibody. This variant VLDLR
      is proposed to be functionally important for internalizing apoE in human brain.
      ApoE is associated with beta-amyloid in senile plaques and plays a role in the
      transport of the beta-amyloid. The presence of VLDLR in myelin may be one
      explanation as to why beta-amyloid does not accumulate in the white matter which
      is rich in VLDLR. Recently, evidences on VLDLR obtained mainly using knock-out or
      transfected mice suggest this receptor to be neither specific for VLDL nor
      functionally important in mammals. However, no variant form of VLDLR was found in
      any tissues of mouse. This variant form of VLDLR should thus be studied in
      greater detail using human tissues or cells.

PMID- 9630509
TI  - Cholinergic amacrine cells are not required for the progression and atropine
      mediated suppression of form-deprivation myopia.
AB  - Muscarinic cholinergic pathways have been implicated in the visual control of
      ocular growth. However, the source(s) of acetylcholine and the tissue(s) which
      regulate ocular growth via muscarinic acetylcholine receptors (mAChRs) remain
      unknown. We sought to determine whether retinal sources of acetylcholine and
      mAChRs contribute to visually guided ocular growth in the chick. Cholinergic
      amacrine cells were ablated by intraocular injections of either ethylcholine
      mustard aziridinium ion (ECMA; a selective cholinotoxin) or quisqualic acid (QA;
      an excitotoxin that destroys many amacrine cells, including those that release
      acetylcholine). Disruption of cholinergic pathways was assessed
      immunocytochemically with antibodies to the acetylcholine-synthesizing enzyme
      choline acetyltransferase (ChAT) and three different isoforms of mAChR, and by
      biochemical assay for ChAT activity. ECMA (25 nmol) destroyed two of the four
      subtypes of cholinergic amacrine cells and attenuated retinal ChAT activity, but
      left retinal mAChR-immunoreactivity intact. QA (200 nmol) destroyed the majority
      of all four subtypes of cholinergic amacrine cells, and ablated most mAChR
      immunoreactivity and ChAT activity in the retina. ECMA and QA had no apparent
      effect on mAChRs or cholinergic fibres in the choroid, only marginally reduced
      choroidal ChAT activity, and had little effect on ChAT activity in the anterior
      segment. Toxin-treated eyes remained emmetropic and responded to form-deprivation
      by growing excessively and becoming myopic. Furthermore, daily intravitreal
      injection of 40 microg atropine for 6 days into form-deprived toxin-treated eyes
      completely prevented ocular elongation and myopia. We conclude that neither
      cholinergic amacrine cells nor mAChRs in the retina are required for visual
      regulation of ocular growth, and that atropine may exert its growth-suppressing
      influence by acting upon extraretinal mAChRs, possibly in the choroid, retinal
      pigmented epithelium, or sclera.

PMID- 9630510
TI  - Use of acridine orange in: flow cytometric evaluation of erythropoietic
      cytotoxicity.
AB  - Cytotoxic insult to bone marrow frequently impairs the proliferating and
      maturational abilities of erythroid cells. Typically, a ratio of enucleated,
      immature polychromatic erythrocytes (PCE) to mature normochromatic erythrocytes
      (NCE) is used to assess cytotoxicity in the micronucleus (MN) assay. The effects
      of cyclophosphamide (CP) on PCE/NCE ratio in rat bone marrow and spleen were
      assessed by a newly developed flow cytometric procedure using glutaraldehyde
      fixed, acridine orange (AO)-stained cells, and compared to manual scoring of
      PCE/NCE in Wright stained slides. Comparison of methods showed that manual and
      flow cytometric determination of PCE were not statistically different. Several
      other parameters of cytotoxicity could be simultaneously assessed because the
      method allowed use of unfractionated whole bone marrow/spleen cell samples.
      Absolute numbers of total nucleated cells (TNC), a ratio of TNC to total
      erythrocytes (TE), and determination of RNA content within the PCE population
      demonstrated dose- and time-dependent effects with CP treatment. Shifts in RNA
      content were particularly sensitive, correctly identifying all CP-treated from
      control specimens, even in those samples where PCE/NCE ratio was similar. The AO
      methodology provided a more rapid, statistically-superior, and thorough approach
      in the assessment of bone marrow and spleen cytotoxicity than the conventional
      manual method of scoring PCE/NCE ratio alone.

PMID- 9630511
TI  - Characterization of the structural and functional changes of hemoglobin in
      dimethyl sulfoxide by spectroscopic techniques.
AB  - Circular dichroism (CD), fourier transform infrared (FTIR), and fluorescence
      spectroscopy were used to explore the effect of dimethyl sulfoxide (DMSO) on the
      structure and function of hemoglobin (Hb). The native tertiary structure was
      disrupted completely when the concentration of DMSO reached 50% (v/v), which was
      determined by loss of the characteristic Soret CD spectrum. Loss of the native
      tertiary structure could be mainly caused by breaking the hydrogen bonds, between
      the heme propionate groups and nearby surface amino acid residues, and by
      disorganizing the hydrophobic interior of this protein. Upon exposure of Hb to
      52% DMSO for ca. 12 h in a D2O medium no significant change in 1652 cm-1 band of
      the FTIR spectrum was produced, which demonstrated that alpha-helical structure
      predominated. When the concentration of DMSO increased to 57%: (1) the band at
      1652 cm-1 disappeared with the appearance of two new bands located at 1661 and
      1648 cm-1; (2) another new band at 1623 cm-1 was attributed to the formation of
      intermolecular beta-sheet or aggregation, which was the direct consequence of
      breaking of the polypeptide chain by the competition of S&z.dbnd6;O groups in
      DMSO with C&z.dbnd6;O groups in amide bonds. Further increasing the DMSO
      concentration to 80%, the intensity at 1623 cm-1 increased, and the bands at
      1684, 1661 and 1648 cm-1 shifted to 1688, 1664 and 1644 cm-1, respectively. These
      changes showed that the native secondary structure of Hb was lost and led to
      further aggregation and increase of the content of 'free' amide C&z.dbnd6;O
      groups. In pure DMSO solvent, the major band at 1664 cm-1 indicated that almost
      all of both the intermolecular beta-sheet and any residual secondary structure
      were completely disrupted. The red shift of the fluorescence emission maxima
      showed that the tryptophan residues were exposed to a greater hydrophilic
      environment as the DMSO content increased. CO-binding experiment suggested that
      the biological function of Hb was disrupted seriously even if the content of DMSO
      was 20%.

PMID- 9630513
TI  - Alteration of neuronal nitric oxide synthase activity and expression in the
      cerebellum and the forebrain of microencephalic rats.
AB  - Microencephalic rats were obtained through gestational (for the forebrain) or
      neonatal (for the cerebellum) administration of the DNA-alkylating agent
      methylazoxymethanol acetate (MAM), which selectively kills dividing cells during
      neurogenesis. In the microencephalic cerebellum the specific activity of calcium
      dependent nitric oxide synthase (NOS) was decreased by 35-40% at 12, 28 and 70
      days of age. Other neurochemical markers not related to granule cells (the
      neuronal population selectively compromised by neonatal MAM treatment), choline
      acetyltransferase (ChAT) and glutamate decarboxylase (GAD) were not decreased,
      but actually increased when determined as specific activity. In agreement with
      the decreased catalytic activity measured in the tube, the expression of neuronal
      NOS protein was attenuated as judged from immunohistochemistry and Western
      blotting. In the microencephalic forebrain, the specific calcium-dependent NOS
      activity measured in homogenates of the whole hemisphere was significantly
      increased as compared to normal animals. Accordingly, immunohistochemistry for
      neuronal NOS, as well as NADPH-diaphorase histochemistry revealed an apparent
      increase in the density of strongly reactive neurons in the underdeveloped cortex
      and striatum of microencephalic rats. The results reported here demonstrate that
      permanent alterations of neuronal NOS activity and expression occur when the
      development of the brain and its neuronal circuits are severely compromised.
      Furthermore, the permanent downregulation of neuronal NOS in the cerebellum of
      microencephalic rats may be exploited for the study of the role of NO in
      mechanisms of synaptic plasticity such as long term depression (LTD).

PMID- 9630512
TI  - Interaction between corticotropin-releasing factor and nitric oxide in mediating
      the response of the rat hypothalamus to immune and non-immune stimuli.
AB  - We sought to determine whether nitric oxide (NO) influences the steady-state gene
      expression of corticotropin-releasing factor (CRF) in the paraventricular nucleus
      (PVN) of the rat hypothalamus and conversely, whether CRF alters the activity of
      PVN neurons containing NO synthase (NOS), the enzyme responsible for NO
      formation. Adult male rats exposed to a 30-min session of mild electrofootshocks
      displayed a significant (P<0.01) increase in mRNA levels of the immediate early
      gene NGFI-B in the parvocellular portion of the PVN, which contains neurons
      expressing CRF. This response was decreased (P<0.01) by pretreatment with l-NAME,
      an arginine derivative that blocks NOS activity. In contrast, the stimulatory
      effect of interleukin-1beta (IL-1beta), injected intracerebroventricularly
      (i.c.v.) 45 and 15 min earlier, on NGFI-B mRNA and CRF hnRNA levels, was not. The
      i.c.v. injection of CRF (1 microg) significantly upregulated transcription of the
      neuronal isoform of NOS in the PVN, while the ability of i.c.v. IL-1beta to
      stimulate this signal was not significantly altered by i.c.v. injection of CRF
      antagonists. These results indicate that even though CRF acts centrally to
      increase PVN NOS mRNA concentrations, this peptide is not required for the effect
      of i.c.v. IL-1beta on these transcripts. On the other hand, the ability of shocks
      to stimulate PVN neuronal activity depends on NO formation. It therefore appears
      that the functional interactions between NO and CRF-dependent pathways is a
      function of the type of homeostatic threat to which the organism is exposed.

PMID- 9630514
TI  - Rapid and efficient cloning of cDNAs encoding Kruppel-like zinc finger proteins
      by degenerate PCR.
AB  - To isolate cDNAs encoding Kruppel-like zinc finger proteins consisting of several
      hundred members, most of which are yet to be identified, from a limited number of
      available cells, we developed a rapid and efficient zinc finger gene cloning
      method based on reverse transcription-polymerase chain reaction (RT-PCR) using
      tagged, degenerate oligonucleotide primers corresponding to the conserved H/C
      link followed by the reverse blue selection to identify clones containing
      properly amplified fragments. More than 5x103 blue colonies were obtained from
      only 1ng of total RNA. Eighty-eight out of 89 clones, which were randomly picked
      up from blue colonies and sequenced, encoded 60 different zinc fingers with the
      expected structure, and among them, only four have been previously described.
      Furthermore, it was possible to rapidly select clones that were differentially
      expressed in a tissue and stimulation-specific manner by a differential screening
      of the zinc-finger cDNA library using probes consisting of distinct sets of the
      zinc-finger PCR products. These results indicate that our PCR-based method is
      quite efficient and suitable for analyzing not only zinc finger genes but also
      other large gene families, especially when the available cells are very limited.

PMID- 9630515
TI  - Effects of prefrontal cortical lesions on neuropeptide and dopamine receptor gene
      expression in the striatum-accumbens complex.
AB  - In the rat, neurochemical, behavioral, and anatomical investigations suggest that
      medial prefrontal cortical input modulates the activity of the basal ganglia. To
      understand how prefrontal dysfunction might alter striatal-accumbens function, in
      situ hybridization histochemistry with S35-labeled oligonucleotide probes was
      used to assess changes in striatal-accumbens gene expression following bilateral
      excitotoxic ibotenic acid (IA) lesions of the rat medial prefrontal cortex.
      Quantitative densitometry was used to measure changes in mRNA levels for
      preproenkephalin A (ENK), D1 dopamine receptor, protachykinin (SubP), glutamic
      acid decarboxylase (GAD65), and D2 dopamine receptor. No differences were found
      between sham and lesion groups for ENK, D1, SubP, or GAD65 mRNA levels in the
      striatum or nucleus accumbens (NAC). D2 receptor mRNA levels were, however,
      significantly higher in the dorsomedial striatum and in the core area of the NAC
      of the lesioned rats. Although the functional significance of increased D2 mRNA
      is unclear, these findings demonstrate that glutamate mPFC projections modulate
      gene expression in relatively regionally-localized subcortical neuronal
      populations.

PMID- 9630516
TI  - Binding of GTP and GDP induces a significant conformational change in the GTPase
      domain of Ffh, a bacterial homologue of the SRP 54 kDa subunit.
AB  - The bacterial Ffh protein is homologous to the SRP54 subunit of the signal
      recognition particle. Ffh plays a key role in the targeting of proteins to the
      membrane and it is composed of a N-terminal domain (N), a middle GTPase (G)
      domain and a C-terminal M domain which has binding sites for SRP RNA and signal
      peptide. The GTP binding and hydrolysis of Ffh is critical to its function. We
      have used protease digestion to probe the conformation of the Mycoplasma mycoides
      Ffh N+G domain. In the absence of nucleotide the protein was comparatively
      sensitive to protease cleavage and we identified sites particularly prone to
      cleavage in a region near the C-terminus of the GTPase domain. However, in the
      presence of GTPgammaS or GDP this region is stabilized and the protein adopts a
      more ordered structure. The pattern of cleavage with GTPgammaS was
      indistinguishable from that when GDP was bound, indicating that the conformation
      of the nucleotide-free form is distinct from that when either GTPgammaS or GDP is
      bound to the protein. The possible functional role of this significant
      conformational change is discussed.

PMID- 9630517
TI  - Gestational and ovarian sex steroid antinociception: synergy between spinal kappa
      and delta opioid systems.
AB  - Pain thresholds are elevated during gestation and following the simulation of
      pregnancy blood levels of estrogen and progesterone (hormone simulated pregnancy;
      HSP). The analgesia associated with both conditions is opioid-mediated and
      results from the activation of spinal cord kappa and delta (but not mu) opiate
      receptors. Blockade of spinal kappa or delta opiate receptors, individually, can
      abolish the antinociception associated with either gestational day 20 or day 19
      of HSP. Surprisingly, during either physiological pregnancy or HSP, the magnitude
      of reduction in the increment in jump thresholds following the combined
      intrathecal application of suboptimum concentrations of kappa and delta
      antagonists is indistinguishable from that observed following their individual
      intrathecal application. These data indicate that gestational and ovarian sex
      steroid-induced antinociception is not simply the sum of the independent
      analgesic effects of spinal kappa and delta opioid systems but requires their
      coincident activation. It is suggested that the synergy that has been reported
      following the exogenous intrathecal application of kappa and delta opioids also
      occurs between their endogenous counterparts and underlies the intrinsic
      analgesia associated with each condition. Utilization of such a mechanism allows
      for significant physiological effects (analgesia) to be achieved with doses of
      relevant substrates (dynorphin and enkephalin) which alone would produce minimal
      receptor activation (and analgesia). This would minimize tolerance and dependence
      formation.

PMID- 9630518
TI  - Spatial and temporal evolution of neuronal activation, stress and injury in
      lithium-pilocarpine seizures in adult rats.
AB  - In order to follow the spatial and temporal evolution of neuronal damage,
      cellular activation and stress responses subsequent to lithium-pilocarpine
      seizures of various durations in the adult rat, we analyzed the expression of Fos
      protein and local cerebral glucose utilization as markers of cellular activation,
      HSP72 immunoreactivity and acid fuchsin staining as indicators of cellular stress
      and injury, and Cresyl violet staining for the assessment of neuronal damage. The
      expression of Fos appeared very early, 2-30 min after the onset of polyspikes and
      intensified during the following 4 h. Fos immunoreactivity was especially high in
      the hippocampus, cerebral cortex, amygdala and anterior olfactory nuclei. Local
      cerebral glucose utilization measured during the second hour of seizures was
      largely increased (350-580%) over control levels in cortical areas, amygdala,
      dentate gyrus, caudate nucleus and mediodorsal thalamus. HSP72 immunoreactivity
      never appeared earlier than 40-50 min after the onset of polyspikes, and was most
      prominent in hippocampal CA3 area, cerebral cortex (except the piriform cortex)
      and anterior olfactory nuclei. Acid fuchsin staining was maximal in the piriform
      cortex and the polymorphic layer of the dentate gyrus. Staining was moderate in
      the sensorimotor cortex and the amygdala. Neuronal damage was extensive in the
      piriform and entorhinal cortices, the hippocampal CA3 area and the polymorphic
      layer of the dentate gyrus, basal amygdala, mediodorsal thalamus and anterior
      olfactory nuclei. In conclusion, the present study shows that brain regions with
      the highest expression of Fos and the largest metabolic activation were also
      highly stained with acid fuchsin and most heavily damaged. Conversely, there is
      no clear relationship between HSP72 expression, cellular activation and neuronal
      damage.

PMID- 9630519
TI  - The NF-kappaB/Rel family of proteins mediates Abeta-induced neurotoxicity and
      glial activation.
AB  - The beta-amyloid peptide (Abeta) is deposited in neuritic plaques which are
      characteristic features of Alzheimer's disease (AD). Prominent neurodegeneration
      and glial activation occurs around these plaques leading to the hypothesis that
      Abeta may play a causative role in the neuronal loss and the inflammatory
      response associated with AD. Here we show that Abeta-induced toxicity of cultured
      fetal rat cortical neurons is associated with internucleosomal DNA fragmentation
      beginning just 6 h after neurons are exposed to Abeta. Additionally, constitutive
      NF-kappaB activity readily measured in fetal rat cortical neurons decreases in a
      concentration- and time-dependent fashion following exposure to Abeta, but there
      is no corresponding decrease in NF-kappaB mRNA or protein (p65). An upregulation
      of both IkappaB alpha protein and mRNA which occurs in cortical neurons exposed
      to Abeta may be responsible for retaining NF-kappaB in the cytoplasm accounting
      for the observed decrease in activated NF-kappaB. The latter is supported by the
      observation that pretreatment of cortical cultures with an antisense
      oligonucleotide to IkappaBalpha mRNA is neuroprotective. In contrast to cortical
      neurons, exposure of rat primary astroglial cultures to Abeta results in a
      concentration- and time-dependent activation of NF-kappaB with subsequent
      upregulation of IL-1beta and IL-6. Our data suggest that Abeta-induced
      neurotoxicity as well as astrocyte activation may be medicated by the NF
      kappaB/Rel family of proteins, and thus alterations in NF-kappaB-directed gene
      expression may contribute to both the neurodegeneration and inflammatory response
      which occur in AD.

PMID- 9630520
TI  - Use of acridine orange in: flow cytometric assessment of micronuclei induction.
AB  - The micronucleus assay is a widely accepted method for evaluation of clastogens
      and aneugens. In the current study, acridine orange (AO) supravital staining was
      adapted for flow cytometric usage to assess micronucleated cells in rat bone
      marrow and spleen. Cyclophosphamide was used as a positive control test compound
      and results were compared to manual scoring in Wright-stained slides. In bone
      marrow, both manual and flow cytometric methods demonstrated positive dose
      response-trends for micronucleated polychromatic erythrocytes (MNPCE).
      Significant elevations in MNPCE were observed at all doses of cyclophosphamide,
      and comparisons between methods in bone marrow were not statistically different.
      The flow cytometric method was more sensitive in spleen samples, showing dose-
      and time-related increases in micronuclei compared with manual scoring. AO proved
      to be a sensitive discriminator of RNA and DNA, allowing distinct separation of
      polychromatic erythrocytes (PCE), normochromic erythrocytes (NCE), total
      nucleated cells (TNC), and micronucleated populations within both PCE and NCE
      regions. These results support the use of AO-based flow cytometry to provide a
      rapid and sensitive indicator of micronuclei inducers.

PMID- 9630521
TI  - The human chromosomal gene for necdin, a neuronal growth suppressor, in the
      Prader-Willi syndrome deletion region.
AB  - Necdin is a growth suppressor expressed in virtually all postmitotic neurons in
      the brain. The human necdin gene, NDN, is maternally imprinted and deleted in the
      Prader-Willi syndrome, a neurobehavioral contiguous gene disorder. Here, we
      isolated and characterized the human chromosomal necdin gene and its promoter
      region. The necdin gene is intronless, and it encodes a protein of 321 amino acid
      residues, four residues shorter than mouse Necdin. By fluorescence in-situ
      hybridization analysis, the necdin gene was localized to chromosome 15q11.2-q12
      within the Prader-Willi syndrome deletion region. CpG islands were found in a
      region extending from the proximal 5'-flanking sequence to the protein coding
      region. The 5'-flanking sequence, which lacks canonical TATA and CAAT boxes,
      possessed a promoter activity in postmitotic neurons derived from murine
      embryonal carcinoma P19 cells. Methylation in vitro of HhaI CpG sites in the
      promoter region reduced the transcriptional activity. These results suggest that
      the necdin gene is silenced through methylation of the CpG island encompassing
      its promoter region.

PMID- 9630522
TI  - The 45 kDa form of glucose transporter 1 (GLUT1) is localized in oligodendrocyte
      and astrocyte but not in microglia in the rat brain.
AB  - We and others have previously reported that glucose transporter 1 (GLUT1)-like 45
      kDa protein is localized to parenchymal cells in the brain. However, the precise
      cellular localization has remained unclear. In the present study, we examined the
      cellular localization of GLUT1 in the rat brain by double immunostaining methods
      and immunoelectron microscopic analysis using a rabbit antiserum specific to
      GLUT1. Western blot analysis of the rat brain revealed that the antiserum
      detected a strong band with a molecular weight of 45 kDa and a weak band of about
      55 kDa, which corresponded respectively to the known molecular weights of the
      GLUT1 proteins in the brain parenchymal cells and the brain microvessels.
      Immunohistochemical staining revealed a large number of GLUT1-immunoreactive
      glial cells and microvessels in almost every region of the brain. Double
      immunofluorescence analysis demonstrated that the GLUT1-like 45 kDa protein
      occurred in many galactocerebroside-positive oligodendrocytes and in some glial
      fibrillary acidic protein (GFAP)-positive astrocytes. No GLUT1-immunoreactivity
      was observed in OX42-positive microglia. Immunoelectron microscopic examination
      confirmed that the GLUT1-immunoreactivity was mainly localized in the cytoplasm
      of the oligodendrocytes and astrocytes. The results indicate that the 45 kDa form
      of GLUT1 protein exists in the glial cells including astrocytes and
      oligodendrocytes.

PMID- 9630523
TI  - Upregulation of calpain activity and expression in experimental allergic
      encephalomyelitis: a putative role for calpain in demyelination.
AB  - The degradation of myelin proteins has been implicated in destabilization of the
      myelin sheath in autoimmune demyelinating diseases such as multiple sclerosis
      (MS). In order to investigate the role of calcium-activated neutral proteinase
      (calpain), which degrades myelin proteins, the activity and expression
      (translational and transcriptional) of this enzyme were examined in spinal cords
      of Lewis rats with experimental allergic encephalomyelitis (EAE), an animal model
      of MS. In addition to calpain, the translational expression of calpastatin
      (endogenous inhibitor of calpain) and extent of neurofilament (NFP) and myelin
      protein degradation were evaluated via Western blotting in controls and rats with
      EAE. The transcriptional expression of millicalpain, microcalpain, and
      calpastatin as examined by RT-PCR was not significantly increased in EAE.
      However, calpain translational expression was increased by 206. 5% while the
      levels of 68 kDa NFP and myelin-associated glycoprotein were decreased by 42.9
      and 39.7%, respectively, in animals with EAE compared to controls. Calpastatin
      isoforms (180, 110, 80, and 68 kDa) were significantly increased in EAE as well.
      The findings of increased activity and translational expression of calpain in EAE
      suggest a major role for this enzyme in myelinolysis associated with autoimmune
      demyelinating diseases.

PMID- 9630524
TI  - Apomyoglobin folding intermediates characterized by the hydrophobic fluorescent
      probe 8-anilino-1-naphthalene sulfonate.
AB  - Folding apomyoglobin intermediates were investigated by optical techniques
      including steady-state fluorescence, frequency domain fluorometry, and absorption
      spectroscopy. The investigated chromophores were the aromatic residues, i.e.,
      tyrosyl and tryptophanyl residues, and the extrinsic probe (8-anilino-1
      naphthalenesulfonate, ANS) which is particularly useful for studying partly
      structured forms appearing in the early stage of protein folding. The emission
      decay of the extrinsic probe as well as resonance energy transfer from
      tryptophanyl residues to ANS permitted to identify and characterize partly folded
      forms obtained under different experimental conditions. The results indicate that
      the intermediates so far detected (I-1 and I-2 states) are distinct structural
      states. The differences concern the solvent accessibility to the aromatic side
      chains and the conformational dynamics of the protein region forming the binding
      site for the extrinsic fluorophore.

PMID- 9630525
TI  - Electrophysiological evidence against a neurotransmitter role of corticotropin
      releasing hormone (CRH) in primary somatosensory cortex.
AB  - The possible neurotransmitter role of corticotropin-releasing hormone (CRH) was
      studied in the primary somatosensory cortex of the rat. Electrical activity of
      single neurones was recorded in layers II-VI of cortex, and in the region of the
      locus coeruleus. Iontophoresis and pressure ejection were employed to locally
      apply CRH, and changes in spontaneous, synaptically driven and iontophoretically
      driven firing were examined. In the cortex, of 62 neurones recorded most (51)
      were completely unaffected by high and prolonged current/pressure ejections of
      CRH. Depression of firing was occasionally seen (8 of 62), while a very few (3)
      were weakly excited. Of 25 cells studied with vibrissal stimulation to evoke
      excitatory synaptic responses, responses in two cells were depressed and in two
      they were enhanced. Activity that was evoked by iontophoretic ejection of
      excitatory amino acids, such as glutamate, was depressed in 6 of 40 cells (none
      were enhanced). Such effects as were seen were weak and often difficult to
      reproduce. The effect of CRH on depressions produced by GABA was also tested in
      four experiments. No effects on the amplitude or duration of the depressions were
      observed. In contrast recordings made in the midbrain, in the region of the locus
      coeruleus, resulted in over half the neurones (11 of 20) showing clear
      reproducible excitatory responses to CRH applications. Solutions used in the
      experiments were analysed using chromatography, radioimmunoassay and bioassay,
      and no significant degradation of the peptide was found compared with the
      synthetic standard (CRH (1-41)). The data provide evidence against CRH acting as
      a neurotransmitter or modulator in primary cortex, suggesting that the CRH which
      is localized in certain types of cortical cells is involved in other processes.

PMID- 9630526
TI  - Genomic organization and promoter characterization of the mouse and human genes
      encoding p62 subunit of the transcription/DNA repair factor TFIIH.
AB  - TFIIH, a multisubunit complex was shown to be involved in several biological
      fundamental mechanisms of the cell: transcription, nucleotide excision repair and
      cell cycle regulation. p62 is one of the six subunits that constitutes the core
      of TFIIH versus the holoenzyme, which contains, in addition, the ternary kinase
      CAK complex. To gain an insight into the regulation of the expression of the
      various subunits of the core, we report here the cDNA cloning and the genomic
      organization of the mouse p62 gene. A promoter analysis of both mouse and human
      genes allow us to localize two start sites and the regulatory regions, thus
      demonstrating a significative conservation among both species. Both promoters
      lack classical elements such as CCAAT and TATA boxes. Analysis of the expression
      of the p62 gene reveals an overexpression in testis tissue for both species.

PMID- 9630527
TI  - Vasopressin-induction of the immediate early gene, NGFI-A, in cultured
      hippocampal glial cells.
AB  - Our earlier autoradiographic work had documented a wide distribution of
      vasopressin receptors in the hippocampus [R.E. Brinton, K.W. Gee, J.K. Wamsley,
      T.P. Davis, H.I. Yamamura, Regional distribution of putative vasopressin
      receptors in rat brain and pituitary by quantitative autoradiography, in: Proc.
      Natl. Acad. Sci. USA, 81 (1984) pp. 7248-7252; C. Chen, R.D. Brinton, T.J. Shors,
      R.F. Thompson, [Arg 8]-Vasopressin-induction of long lasting potentiation of
      synaptic transmission in the dentate gyrus, Hippocampus 3 (1993) 193-203.] which
      suggested the possibility that receptors for vasopressin were present in both
      neurons and glia. In the periphery, vasopressin is a potent mitogen in select
      proliferative cell types [E. Rozengurt, A. Legg, P. Pettican, Vasopressin
      stimulation of mouse 3T3 cell growth, Proc. Natl. Acad. Sci. USA, 76 (1979) pp.
      1284-1287.] which also suggested a possible association between vasopressin
      receptor activation and the proliferative capacity of astrocytes. We therefore
      investigated whether vasopressin would induce the expression of the immediate
      early response gene, NGFI-A (also known as zif/268, ZENK, egr-1, krox 24), which
      is associated with initiation of mitogenesis [M. Sheng, M.E. Greenberg, The
      regulation and function of c-fos and other immediate early genes in the nervous
      system, Neuron, 4 (1990) pp. 477-485.]. Cultured hippocampal glial cells were
      exposed to vasopressin or a selective V1 vasopressin receptor agonist and in situ
      hybridization for NGFI-A mRNA was conducted. Results of these experiments
      demonstrated that vasopressin induced a highly significant dose-dependent
      increase in the number of cells expressing NGFI-A. Studies to determine the
      receptor subtype mediating vasopressin induction of NGFI-A were conducted
      utilizing the specific V1 agonist, [Phe2, Ile3, Orn8]-vasopressin. The V1
      receptor agonist induced a highly significant dose dependent increase in the
      number of grains per NGFI-A positive cell. Time course analysis demonstrated that
      V1 agonist induction of NGFI-A occurred within 5 min, was maximally induced at 15
      min of exposure and exhibited a gradual decline within 30 min of exposure which
      continued to decline over the 60 min time course. Glial cell responsivity was
      selective in that vasopressin and V1 agonist induction of NGFI-A occurred in a
      subpopulation of glial cells. Within a sea of glial cells, vasopressin and V1
      agonist would induce islands of NGFI-A positive cells. Results of combined
      immunocytochemical labeling for the astrocyte specific marker, GFAP, and in situ
      hybridization for NGFI-A demonstrated that V1 agonist-induced NGFI-A expression
      occurred in GFAP positive cells. We observed no evidence for V1 agonist induction
      of NGFI-A in neurons. Collectively, these data document that vasopressin, acting
      via V1 vasopressin receptors, induces a highly significant increase in NGFI-A
      expression in select GFAP positive hippocampal astrocytes. To our knowledge,
      these data are the first report of a vasopressin mediated response in hippocampal
      glial cells. The potential functional significance of these findings is
      discussed.

PMID- 9630528
TI  - Efferent projections of the nucleus accumbens in the rat with special reference
      to subdivision of the nucleus: biotinylated dextran amine study.
AB  - The nucleus accumbens (Acb) of the rat has been divided immunohistochemically
      into shell and core, and further, it was subdivided into several portions in
      relation to functional significance. In this report, the efferent projection of
      each subdivision of the Acb was examined using biotinylated dextran amine as an
      anterograde tracer. In rostral Acb, the dorsomedial shell mainly projected to the
      dorsomedial ventral pallidum (VP), lateral hypothalamus (LH) and substantia nigra
      pars compacta (SNc), while the ventromedial shell projected to the ventromedial
      VP, lateral preoptic area, LH and ventral tegmental area (VTA). The dorsal core
      of rostral Acb projected to the caudate putamen, dorsolateral VP, globus pallidus
      (GP), LH, and substantia nigra pars reticulata (SNr). In the middle to caudal
      Acb, the dorsomedial shell mainly projected to the dorsomedial VP, LH and VTA,
      the ventromedial shell projected to the ventromedial VP, substantia innominata,
      VTA, SNc and retrorubral area, and the ventrolateral shell projected to the
      ventrolateral VP and SNc. Furthermore, the ventromedial shell projected to the
      parabrachial nucleus (PB). The dorsomedial core projected to the dorsal VP, LH,
      SNc and SNr, and the ventral and lateral core sent axons to the dorsolateral VP,
      GP and SNc. From the point of view of projection patterns, shell and core are
      distinct throughout the rostro-caudal extent of the Acb. The ventrolateral shell
      at the caudal Acb was clearly differentiated. A direct projection from the
      ventromedial shell of the Acb to PB was also recognised.

PMID- 9630529
TI  - 5-Hz stimulation of CA3 pyramidal cell axons induces a beta-adrenergic modulated
      potentiation at synapses on CA1, but not CA3, pyramidal cells.
AB  - In mouse hippocampal slices, long-term potentiation (LTP) at Schaffer collateral
      fiber synapses onto CA1 pyramidal cells could be induced by brief trains of 5-Hz
      synaptic stimulation (30 s) or by longer trains of 5-Hz stimulation (3 min)
      delivered during beta-adrenergic receptor activation. In contrast, 5-Hz
      stimulation, either alone or in the presence of the beta-adrenergic receptor
      agonist isoproterenol, failed to induce LTP at associational-commissural (assoc
      com) fiber synapses onto CA3 pyramidal cells. Our results suggest that although
      CA3 pyramidal cells give rise to both the Schaffer collateral fiber synapses in
      CA1 and the assoc-com fiber synapses in CA3, the induction of LTP at these
      synapses may be regulated by different activity- and modulatory neurotransmitter
      dependent processes.

PMID- 9630530
TI  - Genotoxicity of coke-oven and urban air particulate matter in in vitro acellular
      assays coupled with 32P-postlabeling and HPLC analysis of DNA adducts.
AB  - This study is an in vitro part of the ongoing biomarker studies with population
      from a polluted region of Northern Bohemia and coke-oven workers from Czech and
      Slovak Republics. The aim of this study is to compare DNA adduct forming ability
      of chemical compound classes from both the urban and coke-oven extractable
      organic mass (EOM) of airborne particles. The crude extracts were fractionated
      into seven fractions by acid-base partitioning and silica gel column
      chromatography. In in vitro acellular assays we used calf thymus DNA (CT DNA)
      with oxidative (+S9) and reductive activation mediated by xanthine oxidase (+XO)
      under anaerobic conditions. Both the butanol and nuclease P1 versions of 32P
      postlabeling for detection of bulky aromatic and/or hydrophobic adducts were
      used. The results showed that the spectra of major DNA adducts resulting from
      both the in vitro assays are within the fractions similar for both the urban and
      coke-oven samples. The highest DNA adduct levels with S9-activation were detected
      for the neutral aromatic fraction, followed by slightly polar and acidic
      fractions for both samples. With XO-mediated metabolism, the highest DNA adduct
      levels were detected for both the acidic fractions. Assuming additivity of
      compound activities, then the acidic fraction, which in the urban sample
      comprises a major portion of EOM mass (28%), may contain the greatest activity in
      both in vitro assays (39 and 69%, +S9 and +XO, respectively). In contrast, the
      aromatic fraction constituting only 8% of total urban EOM mass may account for
      comparable activity (34%) with organic acids. The highest DNA adduct forming
      activity of the coke-oven sample accounts for the aromatic fraction (82 and 63%,
      +S9 and +XO, respectively) that also contains the greatest portion of the total
      EOM (48%). To characterize some of the specific DNA adducts formed, we coupled
      TLC on 20x20 cm plates with HPLC analysis of 32P-postlabeled adducts. In both S9
      treated samples of the aromatic fraction, we tentatively identified DNA adducts
      presumably diolepoxide-derived from: 9-hydroxy-benzo[a]pyrene (9-OH-B[a]P),
      benzo[a]pyrene-r-7,t-8-dihydrodiol-t-9,10-epoxide[+/-] (anti-BPDE),
      benzo[b,j,k]fluoranthenes (B[b]F, B[j]F, B[k]F), chrysene (CHRY), benz[a]
      anthracene (B[a]A) and indeno[cd]pyrene (I[cd]P). These DNA adducts accounted for
      about 57% of total DNA adducts detected in both S9-treated samples of the
      aromatic fraction. DNA adducts of XO-treated samples were sensitive to nuclease
      P1 and HPLC profiles of the major adducts were markedly different from the major
      adducts of S9-treated samples. However, the combination of TLC and HPLC did not
      confirm the presence of DNA adducts derived from 1-nitropyrene (1 NP), 9
      nitroanthracene (9 NA) and 3-nitrofluoranthene (3 NF) that were detected by GC-MS
      in the slightly polar fraction. We concluded that the chemical fractionation
      procedure facilitates the assessing of DNA adduct forming ability of different
      chemical compound classes. However, based on the results obtained with the whole
      extracts, it does not fulfil a task of the actual contribution of individual
      fractions within the activity of the whole extracts. Our results are the first in
      detecting of DNA adducts derived from urban air and coke-oven particulate matter.

PMID- 9630531
TI  - Agrobacterium tumefaciens beta-glucosidase is also an effective beta-xylosidase,
      and has a high transglycosylation activity in the presence of alcohols.
AB  - Agrobacterium tumefaciens beta-glucosidase, Cbg1 was extensively characterised
      and found to be a retaining aryl-glucosidase and an aryl-xylosidase. Cbg1s
      specificity for p-nitrophenyl beta-d-xylopyranoside was 73% that for p
      nitrophenyl beta-d-glucopyranoside when measured by the ratio kcat/Km. The enzyme
      also hydrolysed p-nitrophenyl beta-d-fucopyranoside, and p-nitrophenyl beta-d
      galactopyranoside with moderate efficiency. The enzyme released only terminal
      glucose from p-nitrophenyl beta-cellobioside and had a 20 000-fold preference for
      its natural substrate coniferin over cellobiose as indicated by the ratio
      kcat/Km. The enzyme was activated in the presence of 20 mM 1-propanol, 1-butanol,
      1-pentanol, 1-hexanol, 1-heptanol, and 1-octanol. In the case of butanol this
      activation was investigated and shown to be due to transglycosylation activity
      with over 80% of p-nitrophenyl beta-d-glucopyranoside being converted to 1-butyl
      beta-d-glucopyranoside in the presence of Cbg1 and 100 mM 1-butanol.

PMID- 9630532
TI  - Acoustic frequency tuning of neurons in the basal forebrain of the waking guinea
      pig.
AB  - The acoustic responses of cells in the basal forebrain were studied in the adult
      waking guinea pig. Frequency receptive fields were obtained across wide frequency
      (0.094-45.0 kHz) and intensity (0-90 dB) ranges. A total of 326 recordings were
      obtained in 26 electrode penetrations from five subjects; 205 from the globus
      pallidus (GP), 98 from the caudate-putamen (CPu) and 23 from the central nucleus
      of the amygdala (ACE). Twenty-nine recordings exhibited acoustic responses (GP=20
      (9.8%); CPu=9 (9.2%); ACE=0). Cells in the regions of the GP that project to the
      primary auditory cortex (ACx) exhibited frequency tuning that was dominantly
      suppressive. Responses in the CPu were excitatory, but poorly tuned. The
      spontaneous rate of discharge of GP cells that yielded complete tuning data was
      positively correlated with power in the beta bands (12-25 and 25-50 Hz) and
      negatively correlated with power in the delta band (1-4 Hz) of the EEG of the
      ACx. These findings suggest that acoustically tuned neurons in the GP that are
      inhibited by tones are involved in the regulation of auditory cortical state,
      possibly promoting deactivation to unimportant sounds, and may be cholinergic in
      nature.

PMID- 9630533
TI  - Thermoresponsiveness of posterior hypothalamic (PH) neurons of rats to scrotal
      and abdominal thermal stimulation.
AB  - The thermoresponsiveness of posterior hypothalamic (PH) neurons to localized,
      incremental thermal heating and cooling between 10-40 degrees C of the abdomen or
      scrotum was determined in urethane anesthetized, male Sprague-Dawley rats whose
      core temperature was maintained at 37 degrees C during testing. PH extracellular
      neuronal activity was recorded along with changes in gastrocnemius muscle EMG
      activity and temperature (Tms, indicative of shivering thermogenesis) and
      intrascapular brown adipose tissue temperature (TIBATs, indicative of non
      shivering thermogenesis). Seventy-five PH neurons were recorded following both
      scrotal and abdominal trials of thermal stimulation. Nine percent of PH neurons
      were classified as warm responsive neurons (WRNs), 20% as cold responsive (CRNs),
      and 71% as temperature nonresponsive neurons (TNRNs), based on their thermal
      coefficients (TCs). Mean TC for warm PH neurons was significantly increased with
      scrotal warming between 30-40 degrees C from the mean TC of the same PH WRNs
      following abdominal warming. Similarly, the thermal coefficient was increased
      (i.e., was more negative) for cold responsive PH neurons to scrotal cooling (20
      10 degrees C) as opposed to the TC of the same PH CRNs for abdominal cooling. No
      shivering thermogenesis (no change in temperature or EMG activity from
      gastrocnemius muscle) or non-shivering thermogenesis (no significant increase in
      IBAT temperatures) occurred with scrotal or abdominal cooling in these 21 degrees
      C acclimatized rats. The results indicate that a small population of PH neurons
      are thermoresponsive to localized physiological changes in temperature of the
      scrotum and abdomen with greater thermoresponsiveness shown of both warm and cold
      PH neurons to scrotal vs. abdominal thermal stimulation.

PMID- 9630534
TI  - Accurate insertional inactivation of lacZalpha: construction of pTrueBlue and
      M13TrueBlue cloning vectors.
AB  - Color selection plasmid and phage vectors based on insertional inactivation of
      the lacZalpha gene fragment have been in wide use for nearly two decades. The
      originals (the pUC and M13mp series) and all subsequent derivatives of these
      vectors contain the same mechanism for insertional inactivation of lacZalpha
      placing the sites for gene interruption between the initiator ATG codon and codon
      7, a region that encodes a functionally nonessential part of the lacZalpha
      complementation peptide. Numerous observations found in the literature and made
      in our laboratory suggest that the color selection process in these vectors does
      not function reliably and that erroneous conclusions about the success of cloning
      experiments are frequently drawn. We have studied the efficiency of lacZalpha
      inactivation by performing insertions at different intervals along the entire
      length of the proximal 60-amino-acid (aa)-coding region of the lacZ gene
      (lacZalpha). Our results show that accurate and reliable inactivation of
      lacZalpha occurs only when insertions are made within the DNA region that encodes
      aa 11-36. Based on these results, novel color selection plasmid and phage
      vectors, pTrueBlue and M13TrueBlue, have been constructed. Application of these
      vectors for gap-free shotgun sequencing of genomic DNA is discussed.

PMID- 9630535
TI  - Regional distribution of glutamic acid decarboxylase (GAD65 and GAD67) mRNA in
      the hypothalamus of male rhesus macaques before and after puberty.
AB  - Glutamic acid decarboxylase (GAD) is the rate-limiting enzyme in the gamma
      aminobutyric acid (GABA) biosynthetic pathway, and is coded for by two mRNAs,
      GAD65 and GAD67. Using in situ hybridization, we examine the distribution pattern
      of both GAD mRNAs in the hypothalamus and thalamus of prepubertal and adult male
      rhesus macaques. Qualitatively, GAD65 and GAD67 mRNAs showed a similar wide, but
      highly specific distribution pattern, supporting the view that GABAergic neurons
      play an important role in modulating neuroendocrine function. However, no
      quantitative difference in the intensity of hybridization signal was detected
      between prepubertal and adult animals in any of the hypothalamic or thalamic
      nuclei. Therefore, although GABAergic neurons are anatomically well-placed to
      control the secretion of gonadotropin-releasing hormone (GnRH) in primates, it is
      unlikely that the onset of puberty and the associated increase in GnRH secretion
      is triggered by a change in GAD gene transcription.

PMID- 9630536
TI  - Stimulant-mediated c-fos induction in striatum as a function of age, sex, and
      prenatal cocaine exposure.
AB  - Induction of the immediate-early gene c-fos by the stimulants cocaine and
      amphetamine (AMPH) was analyzed by Fos immunocytochemistry at different ages in
      the brains of prenatally cocaine-treated and control rats. Cocaine and AMPH
      induced c-fos in patches of striatal neurons during the first postnatal week, and
      thereafter produced a progressively more homogeneous pattern that was more dense
      medially. Quantification of Fos-immunoreactive cells in older rats revealed
      differences related to sex and prenatal cocaine treatment. Both cocaine and AMPH
      produced dose-dependent increases in the number of Fos-immunoreactive cells in
      striatum. Prenatal cocaine exposure resulted in increased Fos in males in
      response to AMPH (2 mg/kg) at P18 and cocaine (10 mg/kg) at 1-2 months. In
      females, prenatal cocaine treatment resulted in a reduced response to cocaine at
      1-2 months. Increased c-fos induction was observed in control females compared to
      control males in response to low doses of stimulants; no such sex difference was
      observed in prenatally cocaine-treated rats. The dopamine D1 antagonist SCH23390
      blocked cocaine-mediated c-fos induction in all groups. The NMDA antagonist MK
      801 blocked cocaine-mediated c-fos induction in the medial striatum. In females
      only, MK-801 pretreatment resulted in a dramatic increase in the number of Fos
      immunoreactive cells in lateral striatum. These findings indicate differences in
      the neural basis of c-fos induction in males and females, and changes in
      stimulant-mediated c-fos induction resulting from prenatal cocaine exposure.

PMID- 9630537
TI  - 1H NMR study of dynamics and thermodynamics of acid-alkaline transition in ferric
      hemoglobin of a midge larva (Tokunagayusurika akamusi).
AB  - One of the components of hemoglobin from the larval hemolyph of Tokunagayusurika
      akamusi possesses naturally occurring substitution at the E7 helical position
      (Leu E7) [M. Fukuda, T. Takagi, K. Shikama, Biochim. Biophys. Acta 1157 (1993)
      185-191]. Its oxygen affinity is almost comparable to those of mammalian
      myoglobins and it exhibits Bohr effect. Both acidic and alkaline forms of the
      ferric hemoglobin have been investigated using 1H NMR in order to gain insight
      into molecular mechanisms for relatively high oxygen affinity and Bohr effect of
      this protein. The NMR data indicated that the acidic form of the protein
      possesses pentacoordinated heme, and that the alkaline form possessing OH-
      appears with increasing the pH value. pH titration yielded a pK value of 7.2 for
      the acid-alkaline transition, and this value is the lowest among the values
      reported so far for various myoglobins and hemoglobins. The kinetic measurements
      of the transition revealed that the activation energy for the dissociation of the
      Fe-bound OH-, as well as the dissociation and association rates, decrease with
      increasing the pH value. These pH dependence properties are likely to be related
      to the Bohr effect of this protein.

PMID- 9630538
TI  - Induction of IGF-1 mRNA expression following traumatic injury to the postnatal
      brain.
AB  - A variety of adult, non-neural tissues respond to injury by increasing expression
      of the gene which encodes for insulin-like growth factor-1 (IGF-1). This response
      is thought to be a key component in the regenerative capacity of these tissues.
      In contrast, the central nervous system (CNS) has relatively little regenerative
      capacity following injury. Interestingly, compared to many non-neuronal tissues,
      little IGF-1 mRNA can be detected in the adult CNS, raising the possibility that
      its lack of regenerative capacity is related its relative lack of IGF-1
      expression. However, in the 2-week-old adolescent CNS IGF-1 mRNA can be detected
      in numerous brain regions. Therefore, the purpose of this study was to determine
      the responsiveness of the IGF-1 gene to injury in adolescent CNS tissue, a period
      in which expression of this gene is relatively abundant. Expression of IGF-1 mRNA
      was measured by means of a sensitive solution hybridization/RNase protection
      assay in the parieto-occipital lobes of 2-week-old and adult mice following
      penetrating injury. Levels of IGF-1 transcript in the injured brains were
      significantly increased above those of controls in both 2-week-old and adult
      brains 3-day post injury and remained elevated for 1 week after injury. These
      observations demonstrate that the adult CNS, like other tissues, can respond to
      injury by increasing expression of IGF-1 mRNA.

PMID- 9630539
TI  - Control of expression by the cellulose synthase (bcsA) promoter region from
      Acetobacter xylinum BPR 2001.
AB  - The 5' upstream region (about 3.1kb) of the cellulose synthase operon (bcs
      operon) has been isolated by cloning from Acetobacter xylinum strain BPR 2001.
      The expression level of the upstream region was determined using sucrose synthase
      cDNA as a reporter gene in the shuttle vector pSA19. The expression occurred with
      the 1.1-kb upstream sequence from the ATG start codon of the bcs operon but not
      with the 241-bp upstream sequence in A. xylinum, although neither the 1.1-kb nor
      the 241-bp upstream sequence caused any expression as a promoter in Escherichia
      coli. The level of expression with the 1. 1-kb upstream sequence in A. aceti was
      75% of that in A. xylinum. These results suggest that the upstream region
      functions as a specific promoter for the Acetobacter genus. The expression was
      reduced by the introduction of the 241-bp upstream region between the lac
      promoter and the reporter gene in E. coli and was not detected in A. xylinum.
      This suggests that the short upstream region composed of 241bp contains the
      site(s) which causes a negative regulation on the transcription for bcs operon.
      The production of recombinant protein with the ribosome-binding site (RBS) of A.
      xylinum obtained from the bcs operon, was reduced to about half in E. coli, and
      that with the site of the lac promoter was also reduced to about half in A.
      xylinum. This shows that a species-specific predominance occurs during
      interaction between mRNA and 16S rRNA in the RBS between A. xylinum and E. coli.

PMID- 9630540
TI  - Effect of naloxone on morphine-induced changes in striatal dopamine metabolism
      and glutamate, ascorbic acid and uric acid release in freely moving rats.
AB  - Recent findings have shown that systemic morphine increases extracellular
      dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA),
      ascorbic acid (AA) and uric acid concentrations in the striatum of freely moving
      rats. The morphine-induced increase in DA oxidative metabolism is highly
      correlated with that of xanthine. In the present study, we evaluated the effects
      of subcutaneous (s.c.) naloxone (1 mg/kg) on morphine-induced changes in DA,
      DOPAC, HVA, 5-hydroxyindoleacetic acid (5-HIAA), AA, uric acid and glutamate in
      the striatum of freely moving rats using microdialysis. Dialysates were assayed
      by high performance liquid chromatography with electrochemical detection or
      (glutamate) ultraviolet detection. Morphine (5-20 mg/kg) given s.c. increased DA,
      DOPAC+HVA, 5-HIAA, AA and uric acid and decreased glutamate dialysate
      concentrations over a 3 h period after morphine. Morphine (1 mM), given
      intrastriatally, did not affect all the above parameters, with the exception of
      an early short-lasting decrease in AA concentration. Naloxone antagonised all
      morphine-induced changes with the exception of AA increase and glutamate decrease
      in dialysate concentrations. Systemic or intrastrial (0.2-2 mM) naloxone
      increased AA and decreased glutamate dialysate concentrations. When given
      intranigrally, morphine (1 mM) increased DOPAC+HVA, AA and uric acid and
      decreased glutamate dialysate concentrations over a 2 h period after morphine; DA
      and 5-HIAA concentrations were unaffected. These results suggest that: (i)
      morphine increases striatal DA release and 5-hydroxytryptamine oxidative
      metabolism by a micro-opioid receptor-mediated mechanism mainly at
      extranigrostriatal sites; (ii) morphine increases DA and xanthine oxidative
      metabolism and affects glutamate and AA release by a micro-opioid receptor
      mediated mechanism acting also at nigral sites; and (iii) a micro-opioid receptor
      mediated mechanism tonically controls at striatal sites extracellular AA and
      glutamate concentrations.

PMID- 9630541
TI  - Feature conjunctions and auditory sensory memory.
AB  - This study sought to obtain additional evidence that transient auditory memory
      stores information about conjunctions of features on an automatic basis. The
      mismatch negativity of event-related potentials was employed because its
      operations are based on information that is stored in transient auditory memory.
      The mismatch negativity was found to be elicited by a tone that differed from
      standard tones in a combination of its perceived location and frequency. The
      result lends further support to the hypothesis that the system upon which the
      mismatch negativity relies processes stimuli in an holistic manner.

PMID- 9630542
TI  - A novel bacterial reversion and forward mutation assay based on green fluorescent
      protein.
AB  - We report the first use of green fluorescent protein (GFP) for mutation
      detection. We have constructed a plasmid-based bacterial system whereby mutated
      cells fluoresce and non-mutated cells do not fluoresce. Fluorescence is monitored
      using a simple hand-help UV lamp; no additional cofactors or manipulations are
      necessary. To develop a reversion system, we introduced a +1 DNA frameshift
      mutation in the coding region of GFP and the resulting protein is not fluorescent
      in Escherichia coli. Treatment of bacteria containing the +1 frameshift vector
      with ICR-191 yields fluorescent colonies, indicating that reversion to the wild
      type sequence has occurred. Site-directed mutagenesis was used to insert an
      additional cytosine into a native CCC sequence in the coding region of GFP in
      plasmid pBAD-GFPuv, expanding the sequence to CCCC. A dose-related increase in
      fluorescent colonies was observed when the bacteria were treated with ICR-191, an
      agent that induces primarily frameshift mutations. The highest dose of ICR-191
      tested, 16 microg/ml, produced a mutant fraction of 16 x 10(-5) and 8.8 x 10(-5)
      in duplicate experiments. The reversion system did not respond to MNNG, an agent
      that produces mainly single-base substitutions. To develop a forward system, we
      used GFP under the control of the arabinose PBAD promoter; in the absence of
      arabinose, GFP expression is repressed and no fluorescent colonies are observed.
      When cells were treated with MNNG or ENNG, a dose-dependent increase in
      fluorescent colonies was observed, indicating that mutations had occurred in the
      arabinose control region that de-repressed the promoter. Treating bacteria with
      100 microg/ml MNNG induced mutant fractions as high as 82 x 10(-5) and 40 x 10-5
      in duplicate experiments. Treating bacteria with 150 microg/ml ENNG induced a
      mutant fraction of 2.1 x 10(-5) in a single experiment.

PMID- 9630543
TI  - Depletion of dopamine in the prefrontal cortex decreases the basal
      electrophysiological activity of mesolimbic dopamine neurons.
AB  - One hypothesis regarding the etiology of schizophrenia proposes that disruption
      of the dopaminergic innervation of the prefrontal cortex leads to an increase in
      dopamine (DA) transmission in subcortical regions. In the present study, we
      examined the effect of 6-hydroxydopamine lesions of the medial prefrontal cortex
      (mPFC) dopamine innervation on the spontaneous electrophysiological activity of
      ventral tegmental DA neurons recorded in vivo. DA cell activity was assessed
      along three dimensions: (1) the relative proportion of DA neurons exhibiting
      spontaneous activity, (2) their basal firing rate, and (3) the mean percentage of
      spikes fired in bursts. In lesioned rats, DA neurons in the ventral tegmental
      area (VTA) exhibited a significantly slower mean firing rate, as well as a
      significant reduction in the percentage of spikes fired in bursts relative to
      controls. In contrast, depletion of DA in the mPFC did not have a significant
      effect on the relative proportion of VTA DA neurons exhibiting spontaneous
      activity. We suggest that by reducing the basal electrophysiological activity of
      VTA DA neurons, mPFC DA depletion may lead to an increase in the level of
      responsivity of the system to excitatory stimuli. Thus, the magnitude of increase
      in action potential-dependent DA release that occurs in response to a challenge
      may be augmented in lesioned rats.

PMID- 9630544
TI  - Over-expression of the 18 kD and 21/23 kD fibroblast growth factor-2 isoforms in
      PC12 cells and Schwann cells results in altered cell morphology and growth.
AB  - Basic fibroblast growth factor (FGF-2) occurs in different isoforms which
      represent alternative translation products from a single mRNA. The question of
      whether the presence of multiple FGF-2 isoforms has physiological implications is
      compelling but unresolved so far. However, it has been shown recently that the
      FGF-2 isoforms are differentially regulated in sensory ganglia and peripheral
      nerve following nerve injury and, moreover, in the adrenal medulla during
      postnatal development and after hormonal stimuli suggesting that the isoforms may
      serve different physiological functions. To investigate isoform-specific effects
      we have established immortalized Schwann cells and PC12 cells stably over
      expressing the 18 kD and the HMW isoforms. We found that the over-expression of
      the different isoforms alters morphology and growth of the Schwann cells. PC12
      cells over-expressing the 18 kD FGF-2 were found to differentiate towards the
      neuronal phenotype whereas over-expression of the HMW isoforms resulted in a
      stabilization of the endocrine phenotype. Taken together, these data corroborate
      the idea of FGF-2 isoform-specific functions.

PMID- 9630545
TI  - A Dictyostelium discoideum homologue to Tcp-1 is essential for growth and
      development.
AB  - Tcp-1 (t-complex polypeptide 1 gene) was first identified in the mouse as
      relevant for tail-less and embryonic lethal phenotypes. Since then, its
      homologous sequences have been isolated in several other species, and the yeast
      Tcp-1 has been shown to encode a molecular chaperon for actin and tubulin. In a
      random sample of genes expressed in the gamete of Dictyostelium discoideum (Dd),
      we encountered a sequence containg the TCP1 motifs. The complete ORF of the gene
      (DdTcp-1) showed more than 60% similarity to TCP-1 of several organisms,
      including human. DdTcp-1 was found to be expressed in both sexually mature and
      immature cells at the growth phase. Although the sexual process itself was not
      affected, antisense interference of this gene resulted in severe retardation of
      cell growth, leading to the complete cessation of division. In addition, the
      antisense transformants stopped asexual development at the finger stage. These
      results suggest an important function of DdTcp-1 in growth and development of
      this organism.

PMID- 9630546
TI  - P450 isoforms in a murine macrophage cell line, RAW264.7, and changes in the
      levels of P450 isoforms by treatment of cells with lipopolysaccharide and
      interferon-gamma.
AB  - The presence of P450 in a murine macrophage cell line, RAW264.7, was investigated
      to clarify the biological role and regulation of P450. Microsomes of RAW264.7
      cells were isolated and subjected to immunoblotting with anti-rat CYP2A1, 2B1,
      and 4A2 antibodies. The microsomes gave staining bands with all these antibodies,
      suggesting the presence of mouse Cyp2a, 2b, and 4a isoforms in RAW264.7. RAW264.
      7 cells were treated with typical inducers of P450 (phenobarbital, clofibrate,
      beta-naphthoflavone and 3-methylcholanthrene). None of these chemicals induced
      these P450s. Stimulation of RAW264.7 cells with lipopolysaccharide (LPS) and
      interferon-gamma (INF-gamma) which increase inducible nitric oxide synthase
      (iNOS) and cytokines in cells decreased Cyp4a protein but not Cyp2a and 2b
      proteins. To identify P450 isoforms in RAW264.7, we used polymerase chain
      reaction (PCR) primers for mouse Cyp2a4, 2a12, 2b9/10, 4a10, and 4a12. Total RNA
      was isolated from these cells and converted to cDNA by reverse transcriptase. PCR
      was done with these primers and the amplified nucleotides were analyzed by a DNA
      sequencer. Only Cyp2b9/10 and 4a12 primers gave clear bands, although all primers
      gave clear bands from liver total RNA. Nucleotide sequences of these products
      amplified by PCR were identical with Cyp2b9 and 4a12. These findings indicate
      that Cyp2b9 and 4a12 were present in a macrophage cell line, RAW264.7, and the
      regulation of P450 by inducers and cytokine differed from that in liver.

PMID- 9630547
TI  - GABAA-benzodiazepine receptors in the striatum are involved in the sedation
      produced by a moderate, but not an intoxicating ethanol dose in outbred Wistar
      rats.
AB  - The role of the dorsal striatum in mediating the sedation produced by a moderate
      (0.75 g/kg) and an intoxicating (1.25 g/kg) EtOH dose was investigated in the
      open field by determining the capacity of direct intrastriatal injections of RY
      008, a partial inverse agonist of the benzodiazepine (BDZ) receptor, to
      antagonize EtOH's effects. SR 95531, the competitive high-affinity GABAA
      antagonist was used as a reference compound. Intrastriatal RY 008 (50, 500 ng)
      and SR 95531 (50 ng) antagonized the sedation produced by the 0.75 g/kg EtOH
      dose. However, RY 008 did not alter the sedation produced by the 1.25 g/kg dose.
      RY 008 alone was without effect. RY 008 also failed to negatively modulate
      GABAergic function at alpha1beta2gamma2 or alpha6beta2gamma2 receptor subtypes
      expressed in Xenopus oocytes. Intrastriatal modulation of the moderate EtOH dose
      was site specific: no antagonism by RY 008 after intraaccumbens infusions was
      observed. The results suggest that central GABAA-BDZ receptors in the dorsal
      striatum play an important role in mediating the sedation produced by a moderate
      EtOH dose in the open field.

PMID- 9630548
TI  - Activity of ventromedial hypothalamic neurons suppressing heart rate is
      associated with paradoxical sleep in the rat.
AB  - Cardiovascular change is one of the common features of paradoxical sleep. Our
      study offers evidence that one of the central areas regulating the circulation
      during sleep is the ventromedial nucleus of the hypothalamus (VMH). We found a
      group of neurons in this hypothalamic nucleus of rats whose electrical activity
      was exclusively increased during paradoxical sleep, and was associated with a
      reduction in heart rate. The onset of this neural activity usually followed that
      of paradoxical sleep. The incidence and duration of paradoxical sleep was
      increased by means of microinjection of carbachol, a cholinergic agonist, into
      the pontine reticular formation, and the neural activity of the VMH still
      appeared in synchrony with carbachol-induced paradoxical sleep. These results
      suggest that the cholinergic paradoxical sleep-inducing mechanism in the pons
      facilitate the excitability of these neurons. We have previously shown that these
      VMH neurons suppress blood pressure and heart rate via inhibition of the
      vasomotor neurons in the medulla oblongata. Taken together, our findings suggest
      that a group of neurons in the VMH suppresses the circulatory system during
      paradoxical sleep.

PMID- 9630549
TI  - Selective increases in serotonin 5-HT1B/1D and 5-HT2A/2C binding sites in adult
      rat basal ganglia following lesions of serotonergic neurons.
AB  - Quantitative autoradiography was used to examine possible adaptive changes in
      serotonin 5-HT1B/1D and 5-HT2A/2C receptor binding sites in adult rat basal
      ganglia, after partial or severe lesions of serotonergic neurons produced by
      intraraphe injections of variable amounts of 5,7-dihydroxytryptamine. In
      controls, the 5-HT1B/1D sites labeled with S-CM-G[125I]TNH2 were evenly
      distributed in the core and the shell of the nucleus accumbens. The density of 5
      HT1B/1D sites was higher in the ventral than dorsal part of the striatum and no
      regional differences were detected along the rostrocaudal axis of the structure.
      The 5-HT2A/2C sites labeled with [125I]DOI were preferentially distributed in the
      mediodorsal striatum and higher densities were detected in the shell than core of
      the nucleus accumbens. Following 5,7-dihydroxytryptamine injections, there were
      no changes in binding of either receptor subtype after partial lesions entailing
      80-90% 5-HT depletions. After severe 5-HT depletions (over 95%), large increases
      in 5-HT1B/1D binding were observed in the substantia nigra (78%), but no changes
      took place in the globus pallidus. Increases in 5-HT1B/1D binding were also
      detected in the shell of the nucleus accumbens (27%). Similar sized increases in
      5-HT2A/2C binding (22%) were restricted to the medial striatum. The present
      results suggest a preferential association between 5-HT1B/1D receptors and the
      striatonigral neurons containing substance P, as indicated by the striatal
      distribution of these receptors and their selective increases in the substantia
      nigra after severe 5-HT deprivation. We recently proposed a similar relationship
      between the 5-HT4 receptors and the striatopallidal neurons containing met
      enkephalin. Moreover, the increases in 5-HT1B/1D binding in the substantia nigra
      and in the shell of the nucleus accumbens reinforce the view of an implication of
      this receptor subtype in motor functions. In contrast, the prominent increases in
      5-HT2A/2C binding after severe 5-HT deprivation as restricted to the medial
      region of the striatum and suggest up-regulation of most probably 5-HT2C
      receptors in a region implicated in cognitive functions.

PMID- 9630550
TI  - Repeated electroconvulsive shock extends the duration of enhanced gene expression
      for BDNF in rat brain compared with a single administration.
AB  - Brain-derived neurotrophic factor (BDNF) is known to modulate synaptic function
      as well as to promote neuronal growth in the adult brain. The aim of the present
      study was to compare the duration of electroconvulsive shock (ECS)-induced BDNF
      gene expression following a single shock (acute ECS) to the more clinically
      relevant situation, where repeated shocks (chronic ECS) are administered. For
      this purpose, we have used quantitative in situ hybridisation with a 35S-labelled
      oligonucleotide probe complementary to mRNAs encoding genes for all forms of
      BDNF. The results confirm previous studies that the administration of ECS
      increases BDNF mRNA abundance in parts of rat brain with particularly marked
      changes in the granule cell layer of the dentate gyrus. We also for the first
      time show the long lasting nature of the increase in BDNF mRNA abundance measured
      after chronic ECS, i.e., significant increases in BDNF mRNA persisted up to 48 h
      after the last shock. Acute ECS at 6 h after the shock produced a slightly more
      pronounced effect on BDNF mRNA abundance than chronic ECS 6 h after the last
      shock. However, this change was not detectable already 24 h after a single ECS.
      These results indicate that repeated ECS induces adaptive changes in BDNF mRNA
      expression.

PMID- 9630551
TI  - Construction and characterization of a partial Mycobacterium tuberculosis cDNA
      library of genes expressed at reduced oxygen tension.
AB  - To determine which bacterial genes could be expressed during tuberculosis in the
      human body, we have prepared and characterized a collection of cDNA clones
      corresponding to genes that are expressed by Mycobacterium tuberculosis during in
      vitro growth in 5% (v/v) oxygen. These cDNA clones were obtained by purifying
      total RNA from M. tuberculosis and cloning small cDNA segments into Escherichia
      coli followed by removal of clones containing ribosomal RNA sequences. From
      approx. 1700 clones, a collection of 170 clones containing non-ribosomal inserts
      were further characterized by PCR amplification. Inserts of more than 180bp were
      verified by Southern hybridization to have corresponding loci in M. tuberculosis
      genomic DNA and their sequence was determined. We describe the genes that have
      been identified using this approach. Multiple independent cDNA clones were
      obtained for two genes, one probably encoding a stable structural RNA and the
      other a homologue of ferritin. RNA levels for these two genes were monitored
      during growth at 20% oxygen, 5% oxygen and in the nearly anaerobic culture
      sediments. No difference in expression levels was found at 5% oxygen compared to
      20% oxygen. RNA levels for the ferritin homologue gene were significantly lower
      in culture sediments. The stable structural RNA, however, showed very high
      expression levels independently of culture conditions.

PMID- 9630552
TI  - Induction of chromosome aberrations in peripheral blood lymphocytes after short
      time inhalation of nitric oxide.
AB  - INTRODUCTION: inhalation of nitric oxide (INO) leads to vasodilation of pulmonary
      vasculature in ventilated regions of the lung. The clinical use of INO, although
      not formally approved as a drug, is widespread. NO may rapidly form nitrogen
      dioxide (NO2) in an oxygen containing gas mixture. NO2 has been shown to induce
      chromosome aberrations and mutations in both animal and bacterial test systems.
      We investigated whether a 2-h exposure to NO would increase frequencies of cells
      with chromosome aberrations in peripheral blood lymphocytes of human volunteers.
      METHODS: 10 volunteers were exposed to inhaled NO 40 parts per million (ppm) for
      2 h. Pre- and post-exposure blood samples were analysed. RESULTS: no
      statistically significant differences (p</=0.05) in chromosome aberrations were
      observed between pre- and post-exposure samples. CONCLUSION: no detectable
      increase of chromosome aberrations in human peripheral blood lymphocytes after 2
      h of NO-inhalation 40 ppm was found.

PMID- 9630553
TI  - Theoretical evidence of the existence of a diazafulvene intermediate in the
      reaction pathway of imidazoleglycerol phosphate dehydratase: design of a novel
      and potent heterocycle structure for the inhibitor on the basis of the electronic
      structure-activity relationship study.
AB  - The reaction mechanism of imidazoleglycerol phosphate dehydratase has not yet
      been clearly revealed. Structural comparison between inhibitors and the substrate
      IGP implicates that the reaction involves a diazafulvene intermediate. Here, we
      present evidence to support this hypothesis by investigating the electronic
      structure-enzyme inhibitory activity relationship on inhibitors with different
      heterocycles using 6-31G** level theory of the ab initio molecular orbital
      method. The calculation results showed that potent inhibitors can be
      distinguished from weak ones by the atomic charge density and by the energy
      levels of the highest occupied lone-pair orbital on the nitrogen atoms in the
      heterocycles. Furthermore, very good correlations (r2=0.8-0.9) were found between
      the charge density on the nitrogen atom and the inhibitory activity. It was also
      revealed that the diazafulvene is electronically similar to the potent
      inhibitors. Thus, these results strongly suggest the existence of the
      diazafulvene as an intermediate possessing tight-binding affinity to the enzyme.
      Based on the electronic structural similarity between the potent inhibitors and
      the proposed intermediate, a novel heterocycle was designed and predicted its
      inhibitory activity prior to the synthesis. Then, activity of synthesized
      inhibitors showed excellent agreement with this prediction. Hence, from the
      theoretical studies and experimental results, we conclude to obtain evidence of
      the hypothesis that the enzyme reaction proceeds via the diazafulvene
      intermediate.

PMID- 9630555
TI  - Sciatic nerve transection evokes lasting up-regulation of angiotensin AT2 and AT1
      receptor mRNA in adult rat dorsal root ganglia and sciatic nerves.
AB  - The angiotensin AT2 receptor is involved in tissue repair and cellular stress
      responses in non-neuronal cells. We have previously observed that the AT2
      receptor-induced neurite formation in PC12W cells is paralleled by a reduced
      neurofilament M expression as it occurs in nerve fiber regeneration. Here we show
      that transection and crush of sciatic nerve fibers of adult rats results in
      dramatic changes of AT2, AT1a and AT1b receptor mRNA in dorsal root ganglion
      neurons (DRGs) and in sciatic nerves 3, 14 and 28 days after axotomy and crush.
      The expression patterns were determined by reverse transcription polymerase chain
      reaction (RT-PCR) assay, and the specificity of amplification products was
      verified by Southern blot hybridization. Whereas axotomy evoked a transient
      increase of AT2 receptor mRNA by more than 1000% after 3 days in proximal and
      after 14 days in distal sciatic nerve stumps (510%), the maximum expression in
      DRGs was observed after 14 days (1100%). Sciatic nerve crush resulted in a time
      dependent up-regulation of AT2 receptor mRNA in sciatic nerve segments coinciding
      with the successful regeneration of nerve fibers. In sciatic nerves, AT1a and
      AT1b receptor mRNA levels were increased within different time-courses and to
      different extents with a maximum expression of 570%. In contrast to AT1a receptor
      mRNAs, AT1b receptor mRNA levels were increased in DRGs by maximally 800%. These
      results suggest that AT2 and AT1 receptor-mediated pathways are involved in
      Schwann cell-mediated myelination and in neuroregenerative responses of DRGs.

PMID- 9630554
TI  - Inhibitors of messenger RNA and protein synthesis affect differently serotonin
      arylalkylamine N-acetyltransferase activity in clock-controlled and non clock
      controlled fish pineal.
AB  - The pineal organ of fish contains photoreceptor cells. In some species (e.g.,
      pike) each photoreceptor is a cellular circadian system which contains a
      photoreceptive unit, the clock and an output unit. In others (e.g., trout) the
      clock is lacking. The main rhythmic output of the pineal photoreceptor is
      melatonin, an internal 'zeitgeber' of the organisms. The nocturnal rise in
      melatonin secretion results from an increase in the activity of the
      arylalkylamine-N-acetyltransferase (AA-NAT) which converts serotonin to N
      acetylserotonin. In the present study we investigated the effects of
      transcription and translation inhibitors on AA-NAT activity in pike and trout
      pineal organs in culture. Cycloheximide, anisomycin, and puromycin inhibited the
      rise in AA-NAT activity observed during the first 2, 4 or 6 h of the dark phase,
      in both species. Actinomycin D was active only in the pike. Six hours of
      treatment during the first half of the night induced inhibition of AA-NAT
      activity, providing that forskolin (an adenylyl cyclase stimulator) was present
      in the culture medium. When the treatment was run for 3, 6 or 12 h, starting at
      midday of a 12L/12D cycle, basal and forskolin-stimulated AA-NAT activity
      (measured at midnight) were dramatically reduced. Such a treatment had no effect
      on trout AA-NAT activity. It is concluded that: (1) the dark-induced rise in AA
      NAT activity and melatonin secretion are dependent on newly synthesized protein
      in both pike and trout pineal; (2) AA-NAT regulation takes place at the
      translational and post-translational levels in both species; (3) AA-NAT
      regulation occurs also at the transcriptional level in the pike, but not in the
      trout; and (4) the cAMP-dependent activation of AA-NAT requires transcription in
      the pike, not in the trout. The presence of a cell population acting as a
      circadian clock in the pike pineal, but not in the trout pineal, can explain the
      difference between these two species. Thus, we suggest that the clock mechanism
      operates at the genetic level in these cells. Further comparative studies between
      clock-controlled and non-clock-controlled pineals might prove interesting to
      demonstrate the difference between these two regulatory pathways.

PMID- 9630556
TI  - A role of subicular and hippocampal afterdischarges in initiation of locomotor
      activity in rats.
AB  - The possible role of a hippocampal afterdischarge (AD) episode in eliciting
      locomotor movements was evaluated in freely moving rats. Electrical stimulation
      of either the ventral subiculum (VSB) or the hippocampal CA1 region evoked an AD
      of 6-50 s in duration, which was followed by an increase in locomotor activity.
      Similar results were also observed after unilateral injection of N-methyl-d
      aspartic acid (NMDA, 0.25 microg or 1 microg), a glutamate receptor agonist, into
      the VSB. Locomotor activity was not observed when either electrical or chemical
      stimulation of the VSB, or electrical stimulation of the CA1 region did not
      elicit an AD. In addition, the duration of the AD was positively correlated with
      the number of locomotor movements induced by stimulation of VSB or CA1 region. It
      is suggested that the hippocampal/subicular AD may be a necessary condition to
      induce locomotor activity by either chemical or electrical stimulation of the
      hippocampus in rats.

PMID- 9630557
TI  - Dissociation kinetics of hemocyanin from Octopus vulgaris.
AB  - The native form of hemocyanin (Hc) from Octopus vulgaris can be completely
      dissociated, at alkaline pH and in the presence of EDTA, from 49S decamers to 11S
      monomers. The kinetics of this process was studied, using a Bio-Logic stopped
      flow system, by following the time dependence of the 450-nm light intensity,
      scattered at 90 degrees, in the 7.9-8.8 pH range. All experimental traces were
      best fitted by a sum of three exponential decay functions. We then tried to best
      fit these decay functions with a series of kinetic models, the best of them
      resulting in one whose dissociation of decamers to monomers takes place in three
      consecutive and irreversible steps, with a highly cooperative step concerning
      dissociation of octamers to dimers, which appears to be the only intermediate
      species. This model was preferred over several others, not only for the best norm
      value but also for the best accordance between each calculated and experimental
      kinetic parameter (rate constants and amplitudes). Although other more complex
      models may be considered, our best fit model represents the simplest one, which
      is able to describe the observed dissociation kinetics.

PMID- 9630558
TI  - Radiosensitivity and repair of the inactive X-chromosome. Insights from FISH and
      immunocytogenetics.
AB  - The inactive X-chromosome provides a unique opportunity to study the role of
      transcriptional activity and chromatin condensation in the repair of chromosome
      damage. We induced chromosome breakage in human lymphocytes with X-rays (1 or 2
      Gy) in either G0 and G1 phase of the cell cycle, and in the presence or absence
      of an inhibitor of double strand break repair, adenine 9-beta-D-arabinofuranoside
      (Ara-A). Chromosomal aberrations involving the X-chromosome were detected by
      means of fluorescence in situ hybridization with an X-chromosome specific red
      painting probe. The activation status of the X-chromosomes involved in the
      chromosomal aberrations was determined by simultaneous immunocytogenetics with
      FITC-conjugated antibodies against BrdUrd incorporated at late S-phase to
      distinguish the late replicating inactive X-chromosome in green-yellow. This
      multicolor approach allowed us to study and compare breakage and the extent of
      repair in the active and inactive X-chromosome. Our data indicate that both
      chromosomes responded with a similar radiosensitivity. This observation was
      consistent at both X-ray doses and at the two stages of the cell cycle analyzed.
      However, the number of chromosomal aberrations involving the inactive X
      chromosome was increased after repair inhibition with Ara-A. The differential
      sensitivity to repair inhibition was observed in G0 after 1 Gy and in G1 after 2
      Gy. Thus, the activation status of the X-chromosome might be a source of
      heterogeneity in breakage and repair. These observations suggest that there is
      heterogeneous repair when the active and the inactive X-chromosomes are compared
      and that the observed fragility is the result of a compromise between the actual
      number of breaks induced in each chromosome and their differential processing.

PMID- 9630559
TI  - The cellular localization of 5-HT2A receptors in the spinal cord and spinal
      ganglia of the adult rat.
AB  - The localization of serotonin2A (5-HT2A) receptors in the adult rat spinal cord
      and dorsal root ganglia was examined by using a polyclonal antibody that
      recognizes the C-terminus peptides of the mouse 5-HT2A receptor. Positive cell
      bodies of 5-HT2A receptor were found in several regions of the spinal cord.
      Generally, large-to-intermediate sized neuronal cell bodies were intensely
      immunolabeled. Motoneurons in the ventral horn were the most intensely labeled.
      Dot-like immunoreactive profiles were located beneath the cell membrane of
      motoneurons. Neuronal somata in the intermediolateral nucleus of the thoracic
      spinal cord were moderately labeled. The immunoreactivity in the dorsal horn was
      weak. A considerable number of glial cell bodies in the white matter were
      immunostained. The majority of both small and large sized neurons were 5-HT2A
      immunopositive in the dorsal root ganglion.

PMID- 9630560
TI  - Highly conserved amino-acid sequence between murine STAT3 and a revised human
      STAT3 sequence.
AB  - Signal transducer and activator of transcription 3 (STAT3) is an important
      mediator of cytokine signaling, whose cDNA and protein sequences have been fully
      characterized. We sequenced the whole human STAT3 cDNA isolated from HepG2 cells.
      The new sequence determined contains 43 nucleotide changes overall, corresponding
      to six modifications at the amino-acid level. The revised amino-acid sequence of
      human STAT3 is now completely identical to the mouse sequence, except for a
      single amino-acid change at position 760. Thus STAT3 now results as one of the
      most evolutionarily conserved among known proteins. By using specific RT-PCR we
      could discriminate between the original sequence and the new variant.
      Amplification of regions within the src-homology domain 2 (SH2) of STAT3, from
      the RNAs of 11 different tissues or cells, revealed only the expression of the
      new SH2 variant. Besides, only this SH2 variant was amplified from human genomic
      DNA. We conclude that the new sequence we have determined in this study
      represents a revised sequence of hSTAT3 or, less likely, a new predominant
      allele.

PMID- 9630561
TI  - Competing processes of cell death and recovery of function following ischemic
      preconditioning.
AB  - The goal of the present study was to determine the neuroprotective efficacy of
      ischemic preconditioning using behavioral, electrophysiological and histological
      endpoints at various time points up to 90 days postischemia. Gerbils were exposed
      to a brief, non-injurious episode of forebrain ischemia (1.5 min) on each of 2
      consecutive days. Three days following this preconditioning procedure, the
      animals received a 5 min occlusion. Other animals underwent sham surgery or a 5
      min occlusion without preconditioning. Ischemic preconditioning appeared to
      provide striking histological protection at both rostral (approximately 80% and
      approximately 67% of sham) and posterior levels of hippocampus (approximately 94%
      and approximately 78% of sham) at 3 and 10 days survival, respectively. However,
      in spite of the near normal number of CA1 neurons, animals displayed marked
      impairments in an open field test of habituation as well as reduced dendritic
      field potentials in the CA1 area. Additionally, in ischemic animals the basal and
      apical dendritic regions of CA1 were nearly devoid of the cytoskeletal protein
      microtubule associated protein 2 (MAP2). Staining levels of MAP2 in
      preconditioned and sham animals were similar. With increasing survival time, open
      field behavior as well as CA1 field potential amplitude recovered. Nonetheless,
      CA1 cell death in ischemic preconditioned animals continued over the 90-day
      survival period (P<0.05, vs. sham levels). Ischemic preconditioning provides a
      significant degree of neuroprotection characterized by a complex interplay of
      protracted cell death and neuroplasticity (recovery of function). These competing
      processes are best elucidated using a combination of functional and histological
      endpoints as well as multiple and extended survival times (i.e., greater than 7
      10 days).

PMID- 9630562
TI  - The pattern of neurotransmitter alterations in LP-BM5 infected mice is consistent
      with glutamatergic hyperactivation.
AB  - To gain insight into the neurochemical pathologies contributing to AIDS dementia
      complex, neurotransmitter levels were measured in the brains of mice infected
      with the LP-BM5 leukemia retrovirus. These mice develop immunologic and cognitive
      deficits analogous to human HIV-1 infection. Met-enkephalin and substance-P
      levels declined approximately 50% in the striatum and hypothalamus beginning as
      early as 4 weeks after infection. Hippocampal met-enkephalin levels were reduced
      to 50% only at 12 weeks after inoculation. Significant decreases (60-70%) in
      acetylcholine concentrations were observed in the striatum, cerebral cortex and
      hippocampus by 12 weeks after virus inoculation, while striatal GABA
      concentrations decreased to 50-60% at 8-12 weeks after infection. Striatal
      somatostatin levels were unchanged. Administration of the NMDA receptor
      antagonists MK-801 or LY 274614 ameliorated the decline in striatal met
      enkephalin levels observed in mice after 8 weeks of infection. This pattern of
      neurotransmitter depletion and the ability of NMDA receptor antagonists to
      attenuate the loss of striatal met-enkephalin are consistent with an excitotoxic
      lesion. Thus, the elevation of glutamate levels secondary to glial activation may
      contribute to the contemporaneous development of cognitive deficits observed in
      mice infected with the LP-BM5 virus.

PMID- 9630563
TI  - Autocrine regulation of neurite outgrowth from PC12 cells by nerve growth factor.
AB  - The PC12 cell line may be used as a model of NGF-induced neuronal
      differentiation. Exposure to NGF is accompanied by extension of neurites,
      cessation of growth and differentiation into cells resembling sympathetic
      neurons. In this study neurite outgrowth from PC12 cells was induced in serum
      free, NGF-free medium conditions. Neurite outgrowth in serum-free conditions was
      abolished by exposure to anti-NGF antisera. Reverse transcription combined with
      polymerase chain reaction (RT-PCR) and in situ hybridization of PC12 cells in
      serum-free medium conditions revealed NGF transcripts. Western blot analysis of
      these cells revealed tyrosine phosphorylation of the high affinity NGF receptor
      (TrkA/gp140) and activation of a downstream signal cascade element, ERK-1/MAP
      kinase. NGF was also detected by a specific enzyme-linked immunoabsorbant assay
      (ELISA) revealing picogram levels of protein in conditioned medium and cell
      lysates. Survival of embryonic rat dorsal root ganglion neurons was maintained in
      cultures grown in this serum-free conditioned medium. This demonstrated that NGF
      may act as an autocrine or paracrine growth factor for PC12 cell differentiation.

PMID- 9630564
TI  - Human Hrs, a tyrosine kinase substrate in growth factor-stimulated cells: cDNA
      cloning and mapping of the gene to chromosome 17.
AB  - Hrs is a 115kDa zinc finger protein which is rapidly tyrosine phosphorylated in
      cells stimulated with various growth factors. We previously purified the protein
      from a mouse cell line and cloned its cDNA. In the present study, we cloned a
      human Hrs cDNA from a human placenta cDNA library by cross-hybridization, using
      the mouse cDNA as a probe, and determined its nucleotide sequence. The human Hrs
      cDNA encoded a 777-amino-acid protein whose sequence was 93% identical to that of
      mouse Hrs. Northern blot analysis showed that the Hrs mRNA was about 3.0kb long
      and was expressed in all the human adult and fetal tissues tested. In addition,
      we showed by genomic Southern blot analysis that the human Hrs gene was a single
      copy gene with a size of about 20kb. Furthermore, the human Hrs gene was mapped
      to chromosome 17 by Southern blotting of genomic DNAs from human/rodent somatic
      cell hybrids.

PMID- 9630565
TI  - Postsynaptic responses of horizontal cells in the tiger salamander retina are
      mediated by AMPA-preferring receptors.
AB  - The postsynaptic responses of sign-preserving second-order retinal neurons
      (horizontal cells (HCs) and off-bipolar cells) are mediated by CNQX-sensitive
      AMPA/KA glutamate receptors. In this study we used receptor-specific allosteric
      regulators of desensitization and selected antagonists to determine the glutamate
      receptor subtypes in tiger salamander horizontal cells. Two approaches were
      employed in this study. The first was to measure postsynaptic currents induced by
      exogenously applied glutamate under voltage clamp conditions in living retinal
      slices; and the second was to record voltage responses controlled by endogenous
      glutamate released from photoreceptors in whole retinas. Application of 100
      microM cyclothiazide (a specific AMPA receptor desensitization blocker) enhanced
      the glutamate-induced current by about 5 fold. In contrast, 300 microgram ml-1 Co
      nA (a specific kainate receptor desensitization blocker), had no effect. GYKI
      52466 (a specific AMPA receptor antagonist) at 30 microM almost completely
      suppressed the glutamate-induced inward current in HCs. Cyclothiazide at 100
      microM depolarized the HC dark membrane potential by about 5 mV and reduced the
      amplitudes of the voltage responses to dim lights, but enhanced the voltage
      responses to bright lights. Cyclothiazide had no effect on either the dark
      potential or the light responses of rods and cones. Con A at 300 microgram ml-1
      had no effect on either the dark potential or the light responses of the HC. GYKI
      52466 (30 microM) hyperpolarized the HC dark membrane potential by about 55 mV
      and almost completely suppressed the light responses. We conclude from these
      results that the postsynaptic glutamate- and light-induced responses in the tiger
      salamander retinal horizontal cells are mediated by AMPA-preferring, and not
      kainate-preferring glutamate receptors. The functional roles of AMPA receptors
      and their desensitization kinetics in visual information processing are
      discussed.

PMID- 9630566
TI  - Factors affecting the genotoxic potency ranking of natural anthraquinones in
      mammalian cell culture systems.
AB  - We had reported that the plant-derived 1,8-dihydroxyanthraquinone derivatives,
      emodin and danthron, were clearly genotoxic in mouse lymphoma L5178Y cells,
      whereas chrysophanol was only weakly genotoxic and physcion not at all. Danthron
      was more potent than emodin. Furthermore, we had found that these compounds bound
      non-covalently to DNA and inhibited topoisomerase II activity. Interestingly, in
      these systems emodin was more potent than danthron. This inversion of the ranking
      prompted us to investigate the underlying mechanism. Since emodin shows a high
      serum-protein binding affinity, horse serum used as a media-supplement in the
      mouse lymphoma genotoxicity assays was analyzed for a potential selective
      scavenging of emodin. Non-covalent DNA-binding in mouse lymphoma L5178Y cells was
      investigated in the absence or presence of serum. In the presence of 10% serum,
      the DNA-binding potency of emodin was markedly reduced and was lower than that of
      danthron. We also applied mutation assays with mouse lymphoma cells and AS52
      cells and varied the serum concentration used. In the absence of serum emodin
      showed slightly higher mutagenicity in AS52 cells than danthron. At reduced serum
      concentration (0.5%) emodin was strongly cytotoxic to the mouse lymphoma cells.
      For chrysophanol and physcion, a considerable reduction of the non-covalent DNA
      binding potency in intact cells was found when compared to danthron, in
      concordance with their lower genotoxic potency. Overall, these data support the
      understanding that the genotoxicity of anthraquinones is, at least in part,
      mediated by non-covalent DNA-binding.

PMID- 9630567
TI  - Purification, molecular characterization and catalytic properties of a
      Pseudomonas fluorescens enzyme having cholinesterase-like activity.
AB  - An enzyme with a cholinesterase (ChE) activity, produced by Pseudomonas
      fluorescens, was purified to homogeneity in a three-step procedure. Analysis by
      non-denaturing and SDS-PAGE, and by isoelectric focusing, indicated that the
      enzyme was a monomer of 43 kDa, with a pI of 6.1. The N-terminal sequence,
      AEPLKAVGAGEGQLDIVAWPGYIEA, showed some similarities with proteins of the ChE
      family and a strong similarity with a protein from Escherichia coli with unknown
      structure and function. Cholinesterase activity at pH 7.0 and 25 degreesC was
      maximum with propionylthiocholine as substrate (kcat,app=670 min-1), followed by
      acetylthiocholine, and significantly lower with butyrylthiocholine. Catalytic
      specificity (kcat/Km) was the same for propionylthiocholine and
      acetylthiocholine, but was two orders of magnitude lower for butyrylthiocholine.
      Kinetics of thiocholine ester hydrolysis showed inhibition by excess substrate
      which was ascribed to binding of a second substrate molecule, leading to non
      productive ternary complex (Km=35 microM, KSS=0.49 mM with propionylthiocholine).
      There was low or no reactivity with organophosphates and carbamates. The enzyme
      inhibited by echothiophate (kII=0.44x102 M-1 min-1) was not reactivated by
      pralidoxime methiodide. However, the P. fluorescens enzyme had affinity for
      procainamide and decamethonium, two reversible ChE inhibitors used as affinity
      chromatography ligand and eluant, respectively. Although similarity of the N
      terminal amino acid sequence of the enzyme with an internal sequence of ChEs is
      weak, its catalytic activity towards thiocholine esters, and its affinity for
      positively charged ligands supports the contention that this enzyme may belong to
      the ChE family. However, we cannot rule out that the enzyme belongs to another
      structural family of proteins having cholinesterase-like properties. The reaction
      of the enzyme with organophosphates suggests that it is a serine esterase, and
      currently this enzyme may be termed as having a cholinesterase-like activity.

PMID- 9630568
TI  - Production and oestrogen regulation of FGF1 in normal and cancer breast cells.
AB  - To investigate the relationship between the FGF1 oestrogen regulation and the
      normal/cancer status of breast cells, we have studied FGF1 17beta-oestradiol
      regulation in normal, transformed and cancerous cells. Normal (NMEC), transformed
      (HBL-100) and cancerous (MCF-7, MDA-MB-231) human mammary epithelial cells
      express different levels of FGF1 mRNAs. Western blot analysis allowed us to
      characterize FGF1 as an 18 kDa form of this polypeptide. Using a neutralizing
      anti-FGF1 antibody we demonstrated that FGF1 is secreted by all mammary cells
      studied and stimulates their proliferation in an autocrine manner. We have
      examined the regulation of FGF1 mRNAs in response to 17beta-oestradiol. FGF1
      mRNAs were upregulated in hormone-dependent NMEC but was not upregulated either
      in hormone-sensitive HBL-100 cells or in the hormone-dependent cancerous cell
      line MCF-7. However, enzyme linked immunosorbent assay indicated an increase of
      FGF1 protein in NMEC, HBL-100 and MCF-7 cells. We have also examined the 17beta
      oestradiol regulation of the four alternatively spliced FGF1 mRNAs: 1.A, 1.B, 1.
      C and 1.D. Only 1.B transcripts were downregulated by 17beta-oestradiol in normal
      cells. These results show that 17beta-oestradiol regulates FGF1 mRNAs in a cell
      specific manner, and that this regulation may be transcriptional or translational
      depending on cell phenotype. The specificity of oestradiol effects was checked
      using its receptor antagonist tamoxifen.

PMID- 9630569
TI  - The release of beta-endorphin and the neuropeptide-receptor mismatch in the
      brain.
AB  - Microprobes bearing immobilized antibodies to the carboxy-terminus of beta
      endorphin were used to study the release of beta-endorphin in the urethane
      anaesthetized rat following electrical stimulation of the ipsilateral arcuate
      nucleus. The microprobes were inserted through the cerebral hemisphere, the
      superior colliculus and the midbrain periaqueductal grey. Since such microprobes
      detect extracellular molecules along their entire length they give information on
      the persistence and spread of compounds following release. Little immunoreactive
      beta-endorphin was detected in the areas of brain sampled during electrical
      stimulation of arcuate nucleus but a remarkable spread throughout the midbrain
      and cerebral cortex occurred within 30 min of the cessation of stimulation. The
      results suggest that although beta-endorphin-containing fibres are absent in many
      parts of the brain, this neuropeptide can access receptors in these sites and it
      is not necessary for release to be directly adjacent to opiate receptors. As such
      it is important evidence supporting the hypothesis of volume transmission as a
      means of neuronal communication. The results also suggest that an important
      mechanism of the transport of beta-endorphin is the cerebrospinal fluid.

PMID- 9630570
TI  - Modulation of mechanically induced calcium waves in hippocampal astroglial cells.
      Inhibitory effects of alpha 1-adrenergic stimulation.
AB  - The effects of different adrenoceptor agonists were investigated on mechanically
      induced Ca2+ waves in astroglial cells in astroglial-neuronal mixed cultures from
      rat hippocampus. In the initial part of the study some properties of the waves
      were characterized. The results show that the initiation of the Ca2+ waves was
      not critically dependent on extracellular Ca2+ but both the calcium signal and
      the propagation area of the calcium wave were significantly reduced when the
      experiments were performed in Ca2+-free buffer. In addition, using the
      phospholipase C (PLC) inhibitor U-73122 (1 microM) and the gap junction uncoupler
      octanol (1 mM), the results showed that the Ca2+ wave propagation required PLC
      activation and functional gap junctions. Further, the data also showed that the
      protein kinase C (PKC) activator phorbol-12-myristate-13-acetate (PMA 150 nM)
      reduced the spreading of the waves. The adrenoceptor agonists isoproterenol (iso;
      beta), phenylephrine (phe; alpha1) and clonidine (clon; alpha2) were evaluated
      for their short-term (<30 s) effects on the wave propagation. The propagation
      area was persistently decreased 1, 3 and 5 min after removal of phe. No effects
      were observed after incubation with iso or clon. Furthermore, using U-73122 or
      PMA together with phe, shortly incubated, the experiments showed that PLC was a
      central regulator in the initial phase of the initiation procedure of wave
      propagation. However, under these conditions PKC was shown not to be involved.
      Instead it appeared that PKC exerted its inhibitory action on the Ca2+ waves in a
      latter phase, after prolonged phe exposure. Taken together, the results show that
      the propagation of Ca2+ waves between astroglial cells in primary cultures can be
      inhibited/regulated in two principally different ways which involve a pronounced
      time component. The results also further point out the adrenergic signaling
      system as an important mediator of dynamic neuron-astroglial information
      exchange.

PMID- 9630571
TI  - Effects of two new lubricants on the mutagenicity of scooter exhaust particulate
      matter.
AB  - Scooter exhaust particulate matter, which is known to be mutagenic, has caused
      heavy air pollution in Shanghai. There are about 400,000 scooters in the city,
      and the number will not significantly decrease for several years. In order to
      manage the pollution caused by scooter emissions, many new catalytic instruments
      and additives were developed. In this paper, the effect of two new lubricants on
      the emission of scooter exhaust particulate matter was evaluated using gas
      chromatography/mass spectrometer (GC/MS), in vitro Salmonella/microsomal assay
      and the in vivo mouse micronucleus assay. The purpose was to learn if these new
      lubricants could have the ability to reduce the exhausts of particulate matter,
      and decrease the mutagenicity of exhaust particles. The domestic Jinniao (TN36L)
      vehicle was chosen as the test vehicle. The results showed that the two new
      lubricants reduced the emission of scooter exhaust particulate matter, including
      the quantity of particulate matter and the organic substances adsorbed onto the
      particles. Compared with the control oil, the two new lubricants reduced the
      emission of particulate matter by 33% and 36%. When using the two new lubricants,
      only 20 and 23 kinds of compounds were identified separately in the organic
      extracts of the exhaust particulate matter by GC/MS, while 45 kinds of compounds
      were detected in the organic extracts of the exhaust particulate matter when the
      control oil was used. Mutagenicities of the extracts of scooter exhaust
      particulate matter were significantly reduced when the two new lubricants were
      used, including the number of histidine-independent colonies over the background
      in TA98 with and without S9 mix in the Salmonella test (F2 sample); and the
      frequencies of bone marrow micronucleated polychromatic erythrocytes in the mouse
      micronucleus assay (both F1 and F2 samples). These results seem to indicate that
      these new lubricants can effectively reduce the pollution of scooter exhaust
      particulate.

PMID- 9630572
TI  - Immunohistochemical localisation of mGluR7 protein in the rodent and human
      cerebellar cortex using subtype specific antibodies.
AB  - Metabotropic glutamate receptors (mGluRs) are a heterogeneous family of G protein
      coupled receptors that are linked to multiple second messenger systems to
      regulate neuronal excitability and synaptic transmission. To characterise the
      protein expression of the two mGluR7 receptor splice variants in human and rat
      cerebellar cortex, antibodies specific to mGluR7 were generated. Antibodies were
      raised against a glutathione-S-transferase fusion protein containing amino acid
      residues located in the extracellular domain common to both the human and rat
      mGluR7 splice variants. These antibodies specifically detected human mGluR7a in
      mammalian cells transfected with this receptor. In agreement with mGluR7 in situ
      hybridisation studies, immunohistochemistry performed at the light microscope
      level revealed that mGluR7 protein expression occurred most prominently in a
      particular population of nerve cells common to both the human and rat, located
      within the cerebellar cortex of gray matter contained within transverse folia.
      Moreover, strong mGluR7-like immunoreactivity was seen in Purkinje cell body
      cytoplasm of the Purkinje cell layer. In the most superficial cerebellar cortical
      layer, the molecular layer, immunostaining was observed in Purkinje cell
      associated proximal and distal dendritic trees. No detectable labelling was
      evident in intrinsic deep cerebellar nuclei known to contain GABAergic terminals
      of projecting Purkinje cell axons. These data are suggestive of a post-synaptic
      location of mGluR7 in this central nervous system structure. In the rodent,
      additional non-Purkinje cells thought to represent inhibitory interneurones were
      labelled at all levels in the molecular layer. mGluR7-like immunoreactivity was
      not associated with glial cells.

PMID- 9630573
TI  - Expression of fos protein in rat brain following administration of a nicotinic
      acetylcholine receptor agonist epibatidine.
AB  - Epibatidine (exo-2-(6-chloro-3-pyridyl)-7-azabicyclo-[2.2.1]heptane), an extract
      of frog skin, is a novel and highly potent agonist for the nicotinic
      acetylcholine (ACh) receptor. The present study was undertaken to examine the
      expression of Fos protein in several rat brain regions following an acute
      administration of epibatidine. Furthermore, we also studied the role of the
      dopamine D1 and D2 receptors and the N-methyl-d-aspartate (NMDA) receptor, and
      nicotinic ACh receptor in the expression of Fos protein by epibatidine. A single
      administration of epibatidine (5, 10, 50 microgram/kg) caused a marked induction
      of Fos-immunoreactivity in the prefrontal cortex, medial striatum, nucleus
      accumbens, amygdala and superior colliculus of rat brain. In these regions,
      pretreatment with SCH 23390 (1.0 mg/kg), a dopamine D1 receptor antagonist, MK
      801 (1.0 mg/kg), a NMDA receptor antagonist, and mecamylamine (5. 0 mg/kg), a
      nicotinic Ach receptor antagonist, inhibited the induction of Fos protein by
      epibatidine (10 microgram/kg). Pretreatment with sulpiride, a dopamine D2
      receptor antagonist, blocked the induction of Fos protein in the prefrontal
      cortex and the core region of accumbens nucleus, but not in the medial striatum
      and the shell division of nucleus accumbens of rat brain. These results suggest
      that epibatidine induced the expression of Fos protein in several regions of rat
      brain, and that dopamine D1 receptor, NMDA receptor, and nicotinic ACh receptor
      may play a role in the expression of Fos protein by epibatidine in rat brain.
      Furthermore, dopamine D2 receptor may, in part, play a role in epibatidine
      induced expression of Fos protein in the prefrontal cortex and the core region of
      nucleus accumbens, but not in the medial striatum and the shell division of
      nucleus accumbens of rat brain.

PMID- 9630574
TI  - Hemisegmental localisation of rhythmic networks in the lumbosacral spinal cord of
      neonate mouse.
AB  - In vitro isolated spinal cord preparations of newborn mice were used to examine
      the localisation of neuronal network(s) involved in the centrally-driven command
      of motor activities. Transections of reduced spinal cord preparations were
      performed under different extracellular bathing conditions, to obtain the
      smallest piece of cord capable of generating spinal motor rhythm. Under normal
      bathing medium, the whole lumbosacral cord from 0 to 2-day-old mice (P0-2 group)
      must be maintained to generate spontaneous motor bursts on lumbar ventral roots.
      In the P3-5 group, however, a three segment long section from the sacral part of
      the cord was still able to produce spontaneous episodes of rhythmic activity.
      Using a Mg2+-free medium to activate quiescent motor neuronal networks,
      transection procedures revealed that a double lumbar segment and a single segment
      (at both lumbar and sacral levels) of the cord continued to exhibit rhythmic
      locomotor-like discharges in P0-2 and P3-5 groups, respectively. In some
      experiments in which isolated reduced preparations did not generate any rhythmic
      activity in ventral roots, central inhibitory influences were blocked by addition
      of bicuculline (20-30 microM) or strychnine (20 microM) to the superperfusate.
      Under these conditions, a slow and synchronous rhythmic activity was typically
      recorded from lumbar and sacral outputs in both P0-2 and P3-5 groups. Finally,
      transection experiments showed that lumbar and sacral hemisegments of the cord
      retained the ability to generate a bicuculline- or strychnine-induced motor
      rhythm. These results suggest that (1) intersegmental connections appear to be
      stronger in P0-2 than in P3-5 group, since under both normal or Mg2+-free bathing
      medium, spinal rhythmic activity was more affected by transection procedures in
      preparations from the younger animals, and (2) neuronal networks producing
      rhythmic motor activities in mouse may be segmentally organised, each hemisegment
      being able to generate its own spinal motor rhythm.

PMID- 9630575
TI  - Death by a dopaminergic neurotoxin, 1-methyl-4-phenylpyridinium ion (MPP+) and
      protection by EGF in GH3 cells.
AB  - In this study we investigated the uptake and effect of a dopaminergic neurotoxin,
      1-methyl-4-phenylpyridinium ion (MPP+) on a clonal strain, GH3 cells, established
      from rat anterior pituitary. Although the level was very low compared with that
      in PC12 cells, a clonal rat pheochromocytoma cell line, there was a detectable
      amount of tyrosine hydroxylase protein in GH3 cells. The levels of monoamines
      including dopamine in GH3 cells were also very low compared with those in PC12
      cells. [3H]MPP+ was incorporated to GH3 cells in a concentration-dependent manner
      and the uptake was inhibited by nomifensine, an inhibitor of dopamine
      transporter. Addition of 200 microM MPP+ stimulated the leakage of lactate
      dehydrogenase (LDH) after a lag of 24 h. Pretreatment with 50 ng/ml of epidermal
      growth factor (EGF), but not nerve growth factor (NGF) or brain-derived
      neurotrophic factor (BDNF), protected against MPP+-induced cell death. These
      findings show that: (1) MPP+ uptake to GH3 cells was via an effective dopamine
      transport system and causes delayed cell death, and (2) EGF protects against MPP+
      induced cell death. A possible role for GH3 cells as dopaminergic neurons is
      discussed.

PMID- 9630576
TI  - Spontaneous inactivation of human lung tryptase as probed by size-exclusion
      chromatography and chemical cross-linking: dissociation of active tetrameric
      enzyme into inactive monomers is the primary event of the entire process.
AB  - A unique property of human mast cell tryptase is its spontaneous inactivation,
      which may be relevant to the regulation of the activity of this enzyme in vivo.
      We have found, using size-exclusion chromatography, that the dissociation of the
      tetrameric active enzyme into the inactive monomer occurred immediately from the
      beginning of the inactivation process and at a rate significantly faster than
      that of the appearance of the inactive, tetrameric form. Eventually, a relatively
      long-lived state of apparent equilibrium between all three forms (active
      tetramer, inactive monomer, inactive tetramer) was reached. When tryptase was
      extensively cross-linked with several heterobifunctional photoactivatable
      reagents, this modified enzyme exhibited a long-term stability in low-ionic
      strength buffer and at elevated temperature, unlike that of the native enzyme.
      Its is suggested that cross-linking prevents the spontaneous inactivation and
      dissociation of tryptase by 'freezing' the normal association state of the enzyme
      and supports the hypothesis that the dissociation of native tetrameric tryptase
      into inactive monomer is the primary event for the entire process of spontaneous
      inactivation of this enzyme.

PMID- 9630577
TI  - Evaluation of genotoxicity of emissions from municipal waste incinerators with
      Tradescantia-micronucleus bioassay (Trad-MCN).
AB  - A 4-year study was conducted to investigate the suitability of the Tradescantia
      micronucleus bioassay (Trad-MCN) to detect genotoxicity of emissions from
      municipal waste incinerators. The genotoxic potential of emissions was assessed
      in three ways: (i) direct fumigation of Tradescantia with diluted incinerator
      emissions, (ii) exposure of Tradescantia to smoke condensates and (iii) in situ
      monitoring of genotoxicity of emissions near a municipal incinerator. The results
      of direct fumigation with smoke emissions varied over the course of the study. In
      1992, significantly higher micronuclei frequencies (MCN) were always observed in
      treated plants than in control plants, regardless of length of fumigation period.
      Furthermore, MCN frequencies were significantly higher in plants fumigated for 24
      h than those fumigated for 8 h, and MCN frequencies were also higher in plants
      fumigated in chamber 1 (low dilution, high stack gas concentration) than those in
      chamber 2 (P<0.05). MCN frequencies were substantially lower in 1993 and 1994,
      and in only 1 out of the 5 fumigation experiments were MCN frequencies
      significantly higher in treated plants than in controls. This drop in MCN
      frequencies was possibly due to the installation of better pollution control
      devices in the incinerator in 1993. Exposure to smoke condensates induced
      significant increases in MCN frequencies in most exposure trials. A drop in MCN
      frequencies over the course of the 4-year study was also attributed to the
      installation of new smoke scrubbing devices. This was further confirmed by the
      chemical analysis of the condensate, which showed a significant reduction in
      organic pollutants after the installation of the new devices. The results of in
      situ monitoring of genotoxicity near a municipal waste incinerator showed that
      MCN frequencies of Tradescantia depended on the distance from the incinerator,
      and the direction of wind. Because exposure periods of 6 h were insufficient to
      elicit significant responses, periods of 10 to 24 h are recommended for in situ
      monitoring.

PMID- 9630578
TI  - Promoter analysis of the human mismatch repair gene hMSH2.
AB  - The human DNA mismatch repair gene homologue hMSH2 is involved in hereditary
      nonpolyposis colorectal cancer. We isolated and characterized the 5' upstream
      region, about 4.4kbp, of the hMSH2 gene. This region contains CpG islands and a
      number of elements involved in constitutive expression, but there is no TATA-box
      nearby the transcription start points. This is the typical structure for many
      promoters of housekeeping genes. Alu sequences and mononucleotide repeats are
      clustered in this region and there are two transcription start points. Deletion
      analysis revealed that less than 300bp was sufficient to initiate transcription.
      Although no mutation that influences promoter activity of this region was found,
      a polymorphism was detected by PCR-RFLP analysis. Because informative cases (C/T
      heterozygous) were relatively high ( approximately 30%), this polymorphism is
      suitable for a marker to examine allelic losses.

PMID- 9630579
TI  - Cell cycle-dependent fluctuation of urokinase-type plasminogen activator, its
      receptor, and inhibitors in cultured bovine mammary epithelial and myoepithelial
      cells.
AB  - Bovine mammary epithelial (BME-UV1, clone E-T and BME-UV, clone E-T2) and
      myoepithelial (BMM-UV, clone m-T2) cell lines were used to study the modulation
      of cell-associated activity of urokinase-type plasminogen activator (u-PA), as
      well as mRNA transcripts of u-PA, its receptor (u-PAR), and inhibitors (PAI-1 and
      PAI-2) during the cell cycle. After release from a growth arrest accomplished by
      growth factor deprivation, the length of the cell cycle was determined as 19-21
      h, with G1, S, and G2+M phases of 6-7, 7-9, and 5-6 h respectively. As the cell
      cycle progressed, accumulated cell-associated u-PA activity increased. Maximal
      activity occurred at the S/G2 boundary and decreased during the G2/M phases. All
      cell lines tested produced plasmin-specific inhibitor(s). Accumulation of u-PA
      mRNA peaked 3 h after stimulation into the growth cycle for m-T2 and E-T and
      during 3-6 h for E-T2 cells. Maximum levels of u-PAR mRNA were observed at 3 h
      for the E-T cell line, 6-9 h for E-T2 cells, and 3-9 h for m-T2 cells. The cell
      cycle distribution of the PAI-1 mRNA was similar to that of u-PA for both
      epithelial cell lines, while for m-T2 cells maximal accumulation of PAI-1 mRNA
      was detected at 3-9 h after growth initiation. The increase of PAI-2 mRNA
      transcription for m-T2 and E-T cells was detected at 3-6 h. The PAI-2 mRNA in E
      T2 cells was under detectable levels. The data indicate that the expression of
      the constituents of the PA system in bovine mammary epithelial and myoepithelial
      cells is not cell type-dependent but is tightly connected to the phase of the
      cell cycle.

PMID- 9630580
TI  - Photoperiodic regulation of hypothalamic neuropeptide messenger RNA expression:
      effect of pinealectomy and neuroanatomical location.
AB  - Seasonal changes in daylength (photoperiod) affect many aspects of mammalian
      physiology and behavior, including reproduction, metabolism, thermoregulation,
      and sleep. The circadian pacemaker in the hypothalamic suprachiasmatic nuclei
      (SCN) regulates these photoperiodic changes. Our studies of the Siberian hamster
      SCN have shown that two types of neuropeptide-containing neurons, vasopressin
      (AVP) and vasoactive intestinal peptide (VIP) neurons, respond to short
      photoperiod by decreasing mRNA expression. The present studies investigated
      whether photoperiodic inhibition of mRNA expression also occurs in somatostatin
      synthesizing neurons in the SCN, depends upon the pineal gland, and occurs in
      neurons in other hypothalamic nuclei. Juvenile Siberian hamsters exposed to
      either long photoperiod (16 h light/day) or short photoperiod (10 h light/day)
      for 2 weeks after weaning, were used for these studies. Coronal sections
      throughout the SCN were prepared and processed for in situ hybridization. The
      results showed that photoperiod decreased the expression of AVP mRNA and VIP mRNA
      in the SCN, as seen previously, but not somatostatin mRNA. Furthermore,
      pinealectomy did not attenuate the short photoperiod inhibition of AVP mRNA and
      VIP mRNA expression in the SCN. Also, short photoperiod inhibition of AVP mRNA
      expression was found in the paraventricular and supraoptic nuclei, as well as in
      the SCN. These results show that short photoperiod inhibition of mRNA expression
      is partially selective among the neuropeptides, but is not restricted to the SCN.
      Furthermore, these findings suggest that photoperiodic regulation of neuropeptide
      mRNA expression is independent of pineal melatonin secretion and gonadal steroid
      secretion.

PMID- 9630581
TI  - Daily variation of muscarinic receptors in visual cortex but not suprachiasmatic
      nucleus of Syrian hamsters.
AB  - Intraventricular administration of carbachol can induce phase shifts in wheel
      running activity in rodents, which depend on circadian phase and are mediated via
      muscarinic cholinergic receptors in Syrian hamsters. We studied the circadian
      variation in binding of [3H]-N-methylscopolamine ([3H]NMS), a hydrophilic
      muscarinic receptor antagonist, in micropunches obtained from the anterior
      hypothalamus and occipital cortex of Syrian hamsters housed in a 14:10 light:dark
      cycle. Binding sites were characterized on cells contained within 1 mm punches
      (obtained from slices 300 microm thick), using a method to selectively detect
      cell surface (functional) receptors. Atropine sulphate was used to determine
      nonspecific binding. Cortex showed a significant daily rhythm in [3H]NMS binding
      with a peak occurring late in the light phase and a trough at lights on, while
      the hypothalamus showed no detectable rhythm. Following suprachiasmatic nucleus
      (SCN) ablation or maintenance in constant darkness, the rhythm in the cortex was
      abolished. These findings suggest that photic information conveyed via the SCN is
      responsible for the receptor binding rhythm in the cortex. Autoradiographic
      studies ([3H]NMS; 2 nM, 3 weeks exposure) clearly revealed both M1 and M2
      subtypes of muscarinic receptors in the region of the SCN and the visual cortex.

PMID- 9630582
TI  - Evidence for the presence of N-acetylaspartylglutamate in cultured
      oligodendrocytes and LPS activated microglia.
AB  - The levels of N-acetylaspartylglutamate (NAAG) were determined by HPLC in
      untreated or lipopolysaccharide (LPS) activated pure astrocyte, oligodendrocyte,
      and microglial cultures derived from developing rat brain. Oligodendrocyte
      cultures expressed 1.52+/-0.12 nmol/microg protein of NAAG, whereas astrocyte
      cultures (0.04+/-0.08 nmol/microg protein) and untreated microglial cultures
      (0.05+/-0.09 nmol/microg protein) contained only trace amounts of the dipeptide.
      After stimulation of microglial cultures for 24 h with LPS, NAAG levels increased
      significantly to 0.37+/-0.12 SD nmol/microg protein. NAAG levels in astrocyte and
      oligodendrocyte cultures remained unchanged after LPS treatment. The findings
      indicate that NAAG is localized to specific glial cell types. Further our results
      suggest that NAAG biosynthesis is induced in microglia, activated by specific
      stimuli.

PMID- 9630583
TI  - Norepinephrine efflux evoked by potassium chloride in cat sympathetic nerves:
      dual mechanism of action.
AB  - Using a dialysis technique, prominent efflux of norepinephrine (NE) from cardiac
      sympathetic nerve endings was observed under local administration of potassium
      chloride (KCl, 100 mM). KCl induced NE efflux was suppressed by omega-conotoxin
      GVIA or desipramine but residual efflux of NE was still detectable. In the
      presence of omega-conotoxin GVIA, KCl induced efflux of NE was augmented by
      pretreatment with reserpine, indicating that this efflux of NE was derived from
      axoplasma with neurotransporter. These data suggest that a KCl induced brisk
      increase in dialysate NE levels might occur as a consequence of exocytotic NE
      release and carrier mediated outward NE transport from nerve endings.

PMID- 9630584
TI  - 4-Chloro-o-phenylenediamine: a 26-week oral (in feed) mutagenicity study in Big
      Blue mice.
AB  - 4-Chloro-o-phenylenediamine (4-C-o-PDA) is a liver carcinogen in mice and was
      found to be weakly mutagenic in the liver of female Big Blue mice after short
      term treatment. In the present study the test compound was given subchronically
      in the diet for 26 weeks at doses of 0, 5000 and 10,000 ppm. The corresponding
      average test substance intake was 2166 mg kg-1 day-1 (males: 1794 mg kg-1 day-1;
      females: 2539 mg kg-1 day-1) and 4610 mg kg-1 day-1 (males: 3926 mg kg-1 day-1;
      females 5925 mg kg-1 day-1) at the low and high dose, respectively. After
      sacrifice, tissues were flash frozen in liquid nitrogen. The lacI mutant
      frequency in the liver was determined from three male and three female mice per
      dose group. The genomically integrated transgene was recovered by packaging into
      lambda phage using Transpack packaging extract (Stratagene, La Jolla, USA)
      followed by infection of Escherichia coli strain SCS-8. Blue mutant plaques were
      scored against a background of clear non-mutant plaques. Food consumption
      decreased initially at 10,000 ppm, while no treatment related effect on food
      intake was observed at 5000 ppm. Body weight gain was found to be decreased in
      all treated animals. Absolute and relative liver weight increased in a dose
      related manner, but only the latter effect was statistically significant. A clear
      dose dependent increase in lacI mutant frequencies was observed in the liver of
      both sexes. The following mutant frequencies (x10(-5)) were observed: 2.73+/-1.01
      (males, untreated), 7.24+/-1.50 (females, untreated), 18.91+/-5.30 (5000 ppm,
      males), 24.91+/-7.58 (5000 ppm, females), 20.47+/-6.68 (10,000 ppm, males) and
      36.17+/-14.98 (10,000 ppm, females). It is therefore concluded that 4-C-o-PDA is
      a strong mutagen in the liver of mice treated subchronically for 26 weeks.

PMID- 9630585
TI  - Distribution of novel CGRP1 receptor and adrenomedullin receptor mRNAs in the rat
      central nervous system.
AB  - Recent cloning studies have isolated receptors which confer specific
      responsiveness to calcitonin gene related peptide (CGRP) and the related peptide
      adrenomedullin. Using in situ hybridisation, we demonstrate the heterogenous
      distribution of the mRNAs of two proposed CGRP1 receptors (RDC-1 and calcitonin
      receptor-like receptor, CRLR) in the rat brain. Adrenomedullin receptor mRNA was
      weakly expressed, principally in the cerebellum. These findings may assist in the
      determination of the function of these largely uncharacterised receptors.

PMID- 9630586
TI  - Mechanism of NADH transfer among dehydrogenases.
AB  - Steady-state and transient-state kinetic experiments have been performed to test
      the proposal that there is a direct (channelled) transfer of NADH from one
      dehydrogenase to another if the two enzymes exhibit distinct chiral coenzyme
      specificity (A-side vs. B-side). The results lend no support to this proposal,
      but are fully consistent with a free-diffusion mechanism of NADH transfer
      irrespective of the chiral specificity of the enzymes.

PMID- 9630587
TI  - Effects of D-AP5 and NMDA microiontophoresis on associative learning in the
      barrel cortex of awake rats.
AB  - Experiments involving single-unit recordings and microiontophoresis were carried
      out in the barrel cortex of awake, adult rats subjected to whisker pairing, an
      associative learning paradigm where deflections of the recorded neuron's
      principle vibrissa (S2) are repeatedly paired with those of a non-adjacent one
      (S1). Whisker pairing with a 300 ms interstimulus interval was applied to 61
      cells. In 23 cases, there was no other manipulation whereas in the remaining 38,
      pairing occurred in the presence of one of three pharmacological agents
      previously shown to modulate learning, receptive field plasticity and long-term
      potentiation: N-methyl-D-aspartic acid (NMDA) (n=8), the NMDA receptor antagonist
      AP5 (n=17) or the nitric oxide synthase inhibitor L-nitro-arginine-N-methyl-ester
      (L-NAME) (n=13). Non-associative (unpaired) experiments (n=14) and delivery of
      pharmacological agents without pairing (n=14) served as controls. Changes in
      neuronal responsiveness to S1 following one of these procedures were calculated
      and adjusted relative to changes in the responses to S2. On average, whisker
      pairing alone yielded a 7% increase in the responses to S1. This enhancement
      differed significantly from the 17% decrease obtained in the non-associative
      control condition and could not be attributed to variations in the state of the
      animals because analysis of the cervical and facial muscle electromyograms
      revealed that periods of increased muscular activity, reflecting heightened
      arousal, were infrequent (less than 4% of a complete experiment on average) and
      occurred randomly. The enhancement of the responses to S1 was further increased
      when whisker pairing was performed in the presence of L-NAME (27%) or NMDA (35%)
      whereas AP5 reduced it to 1%. During the delivery period, NMDA enhanced both
      neuronal excitability and responsiveness to S1 whereas AP5 depressed them.
      However, the effects of both substances disappeared immediately after
      administration had ended. L-NAME did not affect the level of ongoing activity and
      responses to S1 significantly. From these data, we concluded that, since the
      changes in the responses to S1 lasted longer than the periods of both whisker
      pairing and drug delivery, they were not residual excitatory or inhibitory drug
      effects on neuronal excitability. Thus, our results indicate that, relative to
      the unpaired controls, whisker pairing led to a 24% increase in the
      responsiveness of barrel cortex neurons to peripheral stimulation and that these
      changes were modulated by the local application of pharmacological agents that
      act upon NMDA receptors and pathways involving nitric oxide. We can infer that
      somatosensory cerebral cortex is one site where plasticity emerges following
      whisker pairing.

PMID- 9630588
TI  - Medial amygdala stimulation produces a long-lasting excitatory postsynaptic
      potential/spike dissociation in the dentate gyrus in vivo.
AB  - We have previously found that high-frequency stimulation of the medial amygdala
      (MeA) induces long-term potentiation (LTP) of the population spike in the
      perforant path-dentate granule cell synapses of anesthetized rats. In the present
      study, we investigated the influence of MeA stimulation on the relationship
      between the population excitatory postsynaptic potential (pEPSP) and population
      spike in the dentate gyrus. High-frequency stimulation of the MeA produced a
      leftward shift of the E-S curve, in which population spike amplitude was plotted
      against pEPSP slope at various stimulus intensities. MeA-induced population spike
      LTP was also observed under blockade of GABAergic inhibition with picrotoxin.
      These results suggests that MeA stimulation leads to a long-lasting change in the
      internal firing characteristics of the dentate granule cells.

PMID- 9630589
TI  - Mycobacterial Cpn10 promotes recognition of the mammalian homologue by a
      mycobacterium-specific antiserum.
AB  - Self-tolerance, a key feature of the immune system, is still a matter of intense
      debate. We give here evidence for a peculiar behavior of an antiserum against
      Mycobacterium tuberculosis chaperonin 10 (m-Cpn10), which could have implications
      for the mechanism of self-recognition by antibodies against non-self. We show
      that this antiserum can interact in terms of both inhibition of biological
      activity and physical association (immunoprecipitation), with the mammalian
      homologue of m-Cpn10, but only if the bacterial protein is present. Several lines
      of evidence led us to exclude that the two proteins physically associate to form
      heterocomplexes: (1) the behavior of the antiserum was not shared by a monoclonal
      antibody against m-Cpn10; (2) a matrix selective for human Cpn10 (h-Cpn10) did
      not co-purify m-Cpn10; (3) the distribution pattern in non-denaturing isoelectric
      focusing of labeled m-Cpn10 was not altered by the presence of the unlabeled h
      Cpn10. We conclude therefore that the antiserum against M. tuberculosis Cpn10
      also recognizes mammalian Cpn10, with an affinity/avidity regulated by the
      mycobacterial protein, or by the promotion of hetero-oligomerization. This
      emergence of self-recognition in the presence of M. tuberculosis Cpn10 could
      imply a breaking of self-tolerance in situations of infection or vaccination.

PMID- 9630590
TI  - 'Endocannabinoids' and other fatty acid derivatives with cannabimimetic
      properties: biochemistry and possible physiopathological relevance.
AB  - The only endogenous substances isolated and characterised so far that are capable
      of mimicking the pharmacological actions of the active principle of marijuana, (
      )-Delta9-tetrahydrocannabinol, are amides and esters of fatty acids. Some of
      these compounds, like anandamide (N-arachidonoylethanolamine) and 2
      arachidonoylglycerol, act as true 'endogenous cannabinoids' by binding and
      functionally activating one or both cannabinoid receptor subtypes present on
      nervous and peripheral cell membranes. The metabolic pathways and molecular mode
      of actions of these metabolites, as well as their possible implication in
      physiopathological responses, are reviewed here.

PMID- 9630591
TI  - Phosphorylation regulates calpain-mediated truncation of glutamate ionotropic
      receptors.
AB  - Pre-incubation of synaptic membranes with phosphatase inhibitors significantly
      reduces the extent of calpain-mediated truncation of both GluR1 and NR2 subunits
      of AMPA and NMDA receptors, respectively. The same treatment did not modify
      calpain-mediated truncation of spectrin. These results might have important
      implications for mechanisms of synaptic plasticity as the balance of
      kinase/phosphatase activity and calpain has been proposed to regulate synaptic
      efficacy at glutamatergic synapses.

PMID- 9630592
TI  - Interaction of dopamine and cardiac sac modulatory inputs on the pyloric network
      in the lobster stomatogastric ganglion.
AB  - Dopamine and cardiac sac network activity each have strong, and different,
      modulatory actions on the pyloric rhythm in the stomatogastric ganglion of the
      spiny lobster. When combined, the two modulatory inputs have a complex effect.
      Dopamine and cardiac sac activity cancel one another's effects to restore normal
      pyloric activity to 4 of the 6 classes of pyloric neurons. In the remaining two
      pyloric neurons, dopamine's strong modulatory effects are completely overruled
      during cardiac sac network related activity. Possible cellular mechanisms
      underlying these interactions are discussed.

PMID- 9630593
TI  - c-fos gene expression is induced in a subpopulation of striatal neurons following
      a single administration of a dopamine D1-receptor agonist in adult rats lesioned
      with 6-OHDA as neonates.
AB  - The effects of the dopamine D1 receptor agonist, SKF-38393, on the levels of
      mRNAs encoding for the proto-oncogene c-fos and the GABA-synthesizing enzyme
      glutamate decarboxylase (GAD65) were measured by in situ hybridization
      histochemistry in the striatum of adult rats depleted of dopamine as neonates. c
      fos mRNA levels exhibited a prominent increase following the acute systemic
      administration of SKF-38393 in dopamine-depleted but not in normal rats. Double
      labeling in situ hybridization histochemistry using a radioactive c-fos probe and
      a digoxigenin-labeled preproenkephalin (PPE) cRNA probe indicated that c-fos mRNA
      levels were increased by SKF-38393 exclusively in a subpopulation of PPE
      unlabeled neurons. Dopamine-depleted rats exhibited an increase in GAD65 mRNA
      levels relative to control rats. Acute administration of SKF-38393 did not alter
      GAD65 mRNA levels in control or in dopamine-depleted rats. Our results
      demonstrate that an acute administration of a D1-receptor agonist induces c-fos
      but not GAD65 gene expression in a subpopulation of presumed striato
      nigral/entopeduncular neurons. They also suggest that the D1-dependent behavioral
      plasticity exhibited by adult rats depleted of dopamine as neonates is not the
      result of an altered activation of the two subpopulations of striatal efferent
      neurons.

PMID- 9630594
TI  - The assembly of yeast mitochondrial ATP synthase: subunit depletion in vivo
      suggests ordered assembly of the stalk subunits b, OSCP and d.
AB  - The abundance in vivo of each of three subunits b, OSCP and d, components of the
      stalk region of the yeast mitochondrial ATP synthase complex, was manipulated by
      a controlled depletion strategy. Western blots of whole cell lysates were used to
      study the effect of depletion of each of these subunits on the cellular levels of
      other subunits of the enzyme complex. A hierarchy of subunit stability was
      determined and interpreted to indicate the order of assembly of these three
      subunits of the stalk region. Thus, subunit b is assembled first, followed by
      OSCP and then by subunit d.

PMID- 9630595
TI  - The mutagenic versus protective role of vitamin A on the induction of chromosomal
      aberration in human lymphocyte cultures.
AB  - The present study was carried out to evaluate the role of vitamin A (VA) on the
      induction of chromosomal aberrations (CA) in lymphocyte culture system and to
      investigate its modulating effect on chromosomal damage induced by gamma
      irradiation. Lymphocyte cultures from five healthy normal adult males were either
      treated with VA at a dose level of 2.0, 8.0 or 24.0 microg/ml or exposed to gamma
      irradiation of 3.0 Gy, then followed immediately by a treatment with one of the
      above mentioned doses of VA. Non-treated cultures and cultures exposed to gamma
      irradiation served as control for the two sets of experiments. Cultures were set
      up in duplicates and incubated for 48 h for assessment of CA. Treatment with VA
      alone increased CA demonstrating a dose-response effect. Addition of VA to gamma
      irradiated cultures resulted in an inverse protective effect as the low dose of 2
      microg/ml reduced the CA induced by radiation to about 1/3 rd whereas a dose of 8
      microg/ml had a protective effect of 40% of the total damage and the large dose
      of 24 microg/ml had no or little effect. These results suggest that a proportion
      of the added VA may interfere with the radiation induced free radicals and other
      reactive metabolites which elevate CA. On the other hand, excessive amounts of VA
      increased toxicity and reduced effect on repair enzymes.

PMID- 9630596
TI  - Conformational stability studies of the pleckstrin DEP domain: definition of the
      domain boundaries.
AB  - Pleckstrin is the major substrate of protein kinase C in platelets. It contains
      at its N- and C-termini two pleckstrin homology (PH) domains which have been
      proposed to mediate protein-protein and protein-lipid interactions. A new module,
      called DEP, has recently been identified by sequence analysis in the central
      region of pleckstrin. In order to study this module, several recombinant
      polypeptides corresponding to the DEP module and N- and C-termini extended forms
      have been expressed. Using circular dichroism (CD) and nuclear magnetic resonance
      (NMR) techniques, the domain boundaries have been determined that yield a soluble
      and folded pleckstrin DEP domain. This comprises 93 amino acids with an
      alpha/beta fold in agreement with secondary structure predictions. Stability
      studies indicate that the regions surrounding the DEP domain do not contribute to
      its stability suggesting that the phosphorylation sites at S113, T114 and S117
      are in an unstructured region. Identification of the regions of pleckstrin that
      are folded shall facilitate determination of its structure and function.

PMID- 9630597
TI  - Protein-protein interactions between keratin polypeptides expressed in the yeast
      two-hybrid system.
AB  - Keratin filaments are obligatory heteropolymers of type I and type II keratin
      polypeptides. Specific type I/type II pairs are coexpressed in vivo. In contrast,
      all type I/type II pairs assemble into filaments in vitro, but the different
      pairs have different stabilities as demonstrated by treatment with increasing
      concentrations of urea. We have used the yeast two-hybrid system to analyse type
      I/type II interactions in a cellular context. We measured interactions between
      two different keratin pairs and we confirm the findings that K6+K17 form very
      stable heterodimers whereas K8+K18 interactions were weaker. The deletion of head
      domains did not reduce the strength of type I/type II interactions. Rather, the
      affinities were increased and the differences between the two pairs were retained
      in headless mutants. These findings argue against a major role of the head
      domains in directing heterodimer interactions and in defining heterodimer
      stabilities.

PMID- 9630598
TI  - Acute blockade of hippocampal glucocorticoid receptors facilitates spatial
      learning in rats.
AB  - Corticosteroids can facilitate or impair learning and memory processes. We found
      that the glucocorticoid receptor antagonist RU38486 injected locally into the
      dorsal hippocampus dose-dependently improved the performance of male Wistar rats
      in the water maze 24 h after treatment. This observation suggests a discrete
      specificity of hippocampal glucocorticoid receptors in facilitation of memory.

PMID- 9630599
TI  - Functional genetic tests of DNA mismatch repair protein activity in Saccharomyces
      cerevisiae.
AB  - Hereditary non-polyposis colorectal cancer (HNPCC) is associated with mutations
      in four different genes encoding proteins involved in DNA mismatch repair (DMR).
      As many as 30% of the observed sequence variations in human DMR genes predict
      minor alterations in the encoded protein, such as amino acid (aa) replacements or
      small in-frame deletions/insertions. For such sequence variants, a functional
      genetic test will be required to discriminate mutations from polymorphisms. We
      have constructed a series of isogenic yeast strains in which individual genes
      involved in DMR are disrupted, and have standardized an assay which measures GT
      tract stability (Strand et al., 1993) to characterize these gene products.
      Disruptions of the yeast MSH2, MLH1, and PMS1 genes result in, respectively, a
      290-, 450- and 390-fold increased tract instability over the wild type (wt)
      strain under optimized assay conditions. Expression of the wt MSH2 and PMS1 gene
      from plasmids results in complementation of the corresponding chromosomal gene
      disruption. Two different aa replacements which correspond to previously observed
      sequence variants of the human MSH2 gene, and implicated in HNPCC, were created
      in the conserved aa of the yeast MSH2 gene by site directed mutagenesis.
      Conversion of the Pro640 in the yeast protein to Leu resulted in a complete loss
      of protein function. In contrast, a yeast MSH2p protein in which the His658 is
      changed to Tyr retains full function in this in vivo assay. These results
      indicate that the Pro-->Leu and His-->Tyr variants observed in humans constitute,
      respectively, a mutation and a polymorphism. The system described here may be
      used for further structure/function analysis of yeast DMR proteins. Such studies
      may provide insight into the effects that specific sequence variations observed
      in human DMR proteins have on their function.

PMID- 9630600
TI  - Expression of prostaglandin E2 receptor subtypes in the developing sheep
      brainstem.
AB  - Expression in sheep brain of EP transcripts and their ontogeny in the brainstem
      was determined using RT-PCR. Sheep EP subtypes showed high homology (>80%) with
      other species. EP1, EP2, EP3 and EP4 were expressed in spinal cord, medulla,
      pons, diencephalon, hippocampus, pituitary, cortex and cerebellum of the fetal,
      newborn and adult sheep brain. Expression of all four peaked in the newborn,
      whereas fetal and adult expression were similar. A similar ontogeny suggests a
      common regulation.

PMID- 9630601
TI  - K+-current modulated by PO2 in type I cells in rat carotid body is not a
      chemosensor.
AB  - According to the membrane channel hypothesis of carotid body O2 chemoreception,
      hypoxia suppresses K+ currents leading to cell depolarization, [Ca2+]i rise,
      neurosecretion, increased neural discharge from the carotid body. We show here
      that tetraethylammonium (TEA) plus 4-aminopyridine (4-AP) which suppressed the
      Ca2+ sensitive and other K+ currents in rat carotid body type I cells, with and
      without low [Ca2+]o plus high [Mg2+]o, did not essentially influence low PO2
      effects on [Ca2+]i and chemosensory discharge. Thus, hypoxia may suppress the K+
      currents in glomus cells but K+ current suppression of itself does not lead to
      chemosensory excitation. Therefore, the hypothesis that K+-O2 current is linked
      to events in chemoreception is not substantiated. K+-O2 current is an epiphemenon
      which is not directly linked with O2 chemoreception.

PMID- 9630602
TI  - Anti-hyperalgesic effects of tramadol in the rat.
AB  - A new simple behavioral method was used for the evaluation of the anti
      hyperalgesic properties of tramadol in the rat. At the lowest dose (1.25 mg/kg
      i.p.), tramadol did not modify thermal nociceptive thresholds, but it was able to
      prevent and block thermal hindpaw hyperalgesia induced by the tail injection of
      formalin. Our results provide evidence that tramadol blocks hyperalgesic
      behaviors without altering nociception, suggesting that this analgesic drug might
      represent a valid agent against central sensitization.

PMID- 9630603
TI  - Selectivity of lipid-protein interactions with trypsinized Na, K-ATPase studied
      by spin-label EPR.
AB  - The selectivity of the lipid-protein interactions in trypsinised Na, K-ATPase
      membranes from Squalus acanthias has been determined by using EPR spectroscopy
      with different lipid probes spin-labelled on the 14-C atom of the fatty acid
      chain. From measurements at low ionic strength and different pH values, the
      pattern of selectivity is: (stearic acid)->(phosphatidylserine)->(stearic
      acid)0>(phosphatidylcholine)+/-, where superscripts indicate the formal
      electrostatic charge on the lipid headgroup. This is in the same order as that
      determined with native Na,K-ATPase membranes [M. Esmann, D. Marsh, Biochemistry
      24 (1985) 3572-3578]. The selectivity for phosphatidylserine is independent of
      pH, over the range pH 6.0-9. 0, as found also for native membranes. For membranes
      trypsinised in the presence of Rb+ ions, and in the presence of Na+ (which allows
      more extensive proteolysis), the relative association constants, Kr, of all
      lipids are the same as for control membranes, with the exception of ionised
      (stearic acid)- that shows the highest specificity. Therefore, both the
      stoichiometry and the principal determinants of the specificity of lipid-protein
      interaction are preserved on extensive trypsinisation of Na,K-ATPase membranes.
      This has implications for the location and arrangement of those amino acid side
      chains that determine the lipid selectivity of the native Na,K-ATPase.

PMID- 9630604
TI  - Identification of holocarboxylase synthetase (HCS) proteins in human placenta.
AB  - Holocarboxylase synthetase (HCS) is a key enzyme in biotin utilization in
      eukaryotic cells. In a previous work from our laboratory, we described the
      cloning and sequencing of a full-length human HCS cDNA. Due to the presence of
      three candidate sites for initiation of translation, the identification of full
      length HCS proteins remains uncertain. Using antibodies directed against human
      HCS sequences, we have identified, in human placenta, three cytosolic HCS
      proteins, of 86, 82 and 76 kDa. Similar results were observed in lysates of cells
      transfected with an HCS expression vector, as well as with human HCS cDNA
      transcribed and translated in a cell-free system. When anti-HCS antibodies were
      tested for their ability to inhibit HCS enzymatic activity, only the antibody
      directed against a region of HCS from Ile128 to Pro398, and not the antibodies
      against more proximal N-terminal regions inhibited HCS activity, suggesting that
      the sequence from Ile128 to Pro398 is essential for the catalytic activity of
      this enzyme. HCS synthesized in a cell-free system was not translocated into rat
      liver mitochondria. These results suggest that our human HCS cDNA encodes the
      cytosolic forms of the enzyme. These results also suggest that mRNA encoding
      cytosolic HCS can be translated from all three translation initiation codons,
      Met1, Met7 and Met58.

PMID- 9630605
TI  - Antimutagenic structural modification of quinoline assessed by an in vivo
      mutagenesis assay using lacZ-transgenic mice.
AB  - Quinoline, a hepatocarcinogen, mutates the bacterial tester strains in the
      presence of the rat liver microsomal enzymes and induces GST-P (placental
      glutathione S-transferase)-positive foci in a medium-term bioassay system for
      hepatocarcinogenesis. On the other hand, 3-fluorinated quinoline was neither
      mutagenic nor carcinogenic in the same assay systems, whereas, 5-fluoroquinoline
      was mutagenic and carcinogenic. Quinoline was recently demonstrated to be
      mutagenic in an in vivo mutagenicity assay system using the lacZ-transgenic mouse
      (MutaMouse). The present study was undertaken to know whether 3-fluoroquinoline
      would be devoid of in vivo mutagenicity in MutaMouse. Quinoline and 5
      fluoroquinoline were also tested in the same system. Mutagenicity was evaluated
      in the liver, the target organ of quinoline carcinogenesis, and also in the bone
      marrow and testis. The results strongly indicate that fluorine-substitution at
      the position-3 of quinoline could be an anti-genotoxic structural modification of
      quinoline in a wide range of its genotoxic end-points.

PMID- 9630606
TI  - Post-feeding increases in accumbal dialysate dopamine reflect persisting
      increases in dopamine release.
AB  - To determine whether post-feeding increases in dialysate dopamine (DA) in the
      nucleus accumbens are associated with persisting increases in DA release, we
      examined the effect of Ca++-free perfusion on post-feeding dialysate
      concentrations of DA. Post-feeding dialysate DA is entirely Ca++-dependent,
      suggesting the existence of post-feeding increases in exocytotic DA release and
      the ability of microdialysis to monitor dynamic changes in DA release through
      behaviour.

PMID- 9630607
TI  - Dendritic alterations in cortical pyramidal cells in the sparse fur mouse.
AB  - Ornithine carbamoyltransferase deficiency, an X-linked trait, leads to toxic
      hyperammonemia in sparse fur (spf/Y) mice. Quantitative analysis of the basilar
      dendritic tree of layer V pyramidal cells in frontoparietal cortex stained by the
      Golgi Kopsch method revealed a significant decrease in both the complexity of the
      dendritic arbor and in dendritic terminal spine density (60%) in spf/Y mice
      compared with controls. Such reductions may contribute to behavioral dysfunction
      observed in spf/Y mice.

PMID- 9630608
TI  - Regulation of Na+/myo-inositol cotransporter gene expression in hyperglycemic rat
      hippocampus.
AB  - myo-Inositol is accumulated into cells by means of the Na+/myo-inositol
      cotransporter (SMIT), which is of interest because its activity is upregulated by
      hyperosmotic stress. We investigated the effects of hyperglycemia on the
      expression of SMIT mRNA mainly in rat hippocampus. In normal control rats, SMIT
      mRNA signals were predominantly located in the hippocampus, cerebellum and
      choroid plexus. Interestingly, massive induction in the hippocampus was observed
      on the acute stage of induced hyperglycemia in the CA3/CA4, the molecular layer
      of the dentate gyrus, and the hippocampal fissure. The perivascular cells along
      the hippocampal fissure also expressed prominent signals. In the cerebral cortex,
      heterogeneous induction was observed from layers 2 to 6. Furthermore, these
      changes immediately returned to baseline levels after normalization of glucose
      levels. These results suggest that regional specificity of permeability of the
      blood-brain barrier and/or cellular differences in sensitivity to hyperglycemic
      stress would exist in the brain.

PMID- 9630609
TI  - Formation of high axial ratio microstructures from peptides modified with
      glutamic acid dialkyl amides.
AB  - A growing number of amphiphiles are known to form high axial ratio
      microstructures (HARMs) such as the hollow cylindrical microstructures called
      lipid tubules. As a prelude to exploring the potential of HARMs formed from
      lipopeptides in controlled release drug delivery, several microstructure
      formation conditions were investigated. We report the preparation of several
      glutamic acid dialkyl amides with varying alkyl chain lengths bearing a verity of
      peptides (1-4 amino acids) [peptide-Glu-(NHCnH2n+1)2, n=12, 14, 16]. These
      surfactants have been rapidly and efficiently converted into HARMs in aqueous
      buffer at physiological pH and ionic strength, or in buffer containing MeOH or
      EtOH. Helical ribbons and tubular HARMs were produced that were stable for as
      long as 6 months below the phase transition temperatures of the compounds. To
      estimate the stability of HARMs in vivo, HARMs formed from (Pro)3-Glu(NHC16H33)2
      were incubated with DOPC liposomes or fetal calf serum at 40 degreesC. HARM size
      and shape did not change significantly, suggesting that such lipopeptide
      particles can retain their morphology long enough in vivo to be useful as drug
      delivery vehicles.

PMID- 9630610
TI  - The intron 5-inserted form of rat erythropoietin receptor is expressed as a
      membrane-bound form.
AB  - The cDNA encoding an intron 5-inserted form of the erythropoietin receptor (I5Epo
      R) has been cloned from rat. DNA sequence analysis reveals that the insertion of
      intron 5, which consists of 79 bp, causes a shift in reading frame and results in
      termination in the region of exon 7. The deduced amino acid sequence is composed
      of 316 amino acid residues, which is a molecular weight of 34220. To study the
      function of rat I5Epo-R, we established a Chinese hamster ovary cell line
      expressing rat I5Epo-R. Western blot analysis and binding studies with 125I
      recombinant human erythropoietin showed that the transfected cells expressed rat
      I5Epo-R with a molecular size of 36 kDa as a membrane-bound form, but not as a
      soluble form, and had a single class of binding sites with a Kd of 700 pM.

PMID- 9630611
TI  - Recombinant adeno-associated virus vector: use for transgene expression and
      anterograde tract tracing in the CNS.
AB  - We used a recombinant adeno-associated virus vector (AAV) to deliver a foreign
      gene, green fluorescent protein (GFP), into mature neurons in adult rat CNS in
      vivo. Microinjections of AAV as small as 50 nl transduced hundreds of neurons at
      the injection site. There was virtually no retrograde transport as fewer than one
      neuron per brain was found distant from the injection site that exhibited GFP
      immunoreactivity. The gene product, GFP, filled the entire neuronal cytoplasmic
      compartment; GFP immunoreactivity was robust in cell bodies, axons, and nerve
      terminals. There was no tissue damage at the injection sites or pathogenicity
      indicated by changes in astrocytic or microglial markers. There was no
      inflammatory response as judged by leukocytic invasion. Gene expression in
      transduced cells was robust and apparently permanent: there was no evidence of
      phenotypic reversion up to 12 weeks following infection. AAV is an excellent
      vector for introducing foreign genes into mature CNS neurons. Not only might it
      be an ideal vehicle for gene therapy, but also the GFP-containing AAV presents a
      new strategy for tracing long axonal pathways in the CNS, which is difficult with
      current tracers (PHAL, biotinylated dextrans).

PMID- 9630612
TI  - Diversity of sequence haplotypes associated with beta-thalassaemia mutations in
      Algeria: implications for their origin.
AB  - We report the allelic sequence polymorphism associated with seven beta
      thalassaemia mutations. Thirty-two DNAs originating from Algeria and 12 DNAs from
      Sardinia and Sicily were investigated. Their analysis revealed an association
      with a unique haplotype for three beta-thalassaemia mutations (-29, IVS-I-2 and
      IVS-I-1). It seems clear that these mutations have a unicentric origin. The
      presence of the -29 mutation could be explained by migration and founding effect.
      However, the local origin of IVS-I-2 seems clear. The four other mutations, FS6,
      IVS-I-6, IVS-I-110 and stop39 were found to be associated with at least two
      different sequence haplotypes. The likelihood of so many recurrent nucleotide
      dimorphisms in different lineages as a consequence of random mutation is very
      low; it is supported neither by the analysis of equivalent regions in other
      primates, nor by the presence of highly mutable sites such as CpG dinucleotides.
      The fact that these mutations are found exclusively in the Mediterranean area is
      not in favour of a recurrent origin of the mutation. The diversity is far more
      important for the preponderant thalassaemia mutations of the Mediterranean area
      and is higher in the 5' part of the beta-globin gene. Hence, the IVS-I-110, the
      preponderant beta-thalassaemia in the Eastern Mediterranean, probably emerged in
      the extension of the fertile crescent. For the stop39, all the data support the
      hypothesis of a West-Mediterranean origin. The diversity of haplotypes would then
      be generated by recombination events (crossing-over or gene conversions) between
      the original beta-thalassaemia chromosome and the other chomosomal structures
      present in the normal population.

PMID- 9630613
TI  - Direct evidence for the link between monoaminergic descending pathways and motor
      activity: II. A study with microdialysis probes implanted in the ventral horn of
      the spinal cord.
AB  - In order to define precisely the relation between descending monoaminergic
      systems and the motor system, we measured in the ventral horn of spinal cord of
      adult rats the variations of extracellular concentrations of 5-HT, 5-HIAA, DA and
      MHPG. Measurements were performed during rest, endurance running on a treadmill,
      and a post-exercise period, with microdialysis probes implanted permanently for
      45 days. We found a slight decrease in both 5-HT and 5-HIAA during locomotion
      with a more marked decrease during the post-exercise period compared to the mean
      of rest values. In contrast, the concentration of DA and MHPG increased slightly
      during the exercise and decreased thereafter. These results, when compared with
      those of a previous study, which measured monoamines in the spinal cord white
      matter [C. Gerin, D. Becquet, A. Privat, Direct evidence for the link between
      monoaminergic descending pathways and motor activity: I. A study with
      microdialysis probes implanted in the ventral funiculus of the spinal cord, Brain
      Res. 704 (1995) 191-201], highlight the complex regulation of the release of
      monoamines that occurs in the ventral horn.

PMID- 9630615
TI  - Ibogaine acts at the nicotinic acetylcholine receptor to inhibit catecholamine
      release.
AB  - In an effort to determine mechanisms of action of the putative anti-addictive
      agent ibogaine, we have measured its effects on catecholamine release in a model
      neuronal system, cultured bovine chromaffin cells. Various modes of stimulating
      catecholamine release were used including nicotinic ACh receptor activation,
      membrane depolarization with elevated K+ and Na+ channel activation with
      veratridine. In addition, because ibogaine has been reported to interact with
      kappa opioid receptors, we tested whether kappa receptor antagonists could
      reverse ibogaine's effects on catecholamine release. Ibogaine, at low
      concentration (<10 microM) was found to selectively inhibit nicotinic receptor
      mediated catecholamine release, while having no significant effect on release
      evoked by either veratridine or membrane depolarization with elevated K+. The
      inhibitory actions of ibogaine and the kappa agonists were not reversed by
      preincubation with the opioid antagonists nor-binaltorphimine or naltrexone,
      suggesting that these inhibitory effects are not mediated by the kappa opioid
      receptor. The effects of low dose (10 microM) ibogaine were rapidly reversible,
      while the inhibitory effects of higher ibogaine doses persisted for at least 19 h
      following ibogaine washout. The results provide evidence for a mechanism of
      action ibogaine at the nicotinic ACh receptor. The results are consistent with a
      model in which the initial high transient brain concentrations (100 microM) of
      ibogaine act at multiple cellular sites and then have a selective action at the
      nicotinic ACh receptor cation channel following its metabolism to lower brain
      concentrations. The present findings are relevant to potential anti-addictive
      actions of ibogaine and to the development of drugs to combat nicotine addiction.

PMID- 9630614
TI  - Modulation of ACh receptor currents by arachidonic acid.
AB  - The present study investigated the effects of arachidonic acid on Torpedo (alpha
      beta gamma delta) and neuronal nicotinic acetylcholine (ACh) receptors (chick
      alpha7; rat alpha7, alpha3 beta2, alpha3 beta4, alpha4 beta2, and alpha4 beta4).
      Arachidonic acid (10 microM) depressed currents through normal Torpedo ACh
      receptors during treatment and afterward, persistently (>/=30 min) potentiated
      the currents. The potentiation was blocked by the selective protein kinase C
      (PKC) inhibitor, GF109203X or PKC inhibitor peptide (PKCI). The depression was
      not inhibited by any protein kinase inhibitor examined here, but greater in Ca2+
      free extracellular solution. Arachidonic acid also potentiated currents through
      mutant Torpedo ACh receptors lacking PKC phosphorylation sites at Ser333 on the
      alpha subunit and Ser377 on the delta subunit without depression, but otherwise,
      it depressed currents through mutant receptors replacing of each Ser by
      negatively charged amino acid residue, possibly that mimics PKC phosphorylation
      of the receptors. These results suggest that the depression was due to the direct
      blocking effect on Ca2+-modulatory sites, which was accelerated under conditions
      of the receptors phosphorylated by PKC, and that the potentiation was caused by
      PKC activation, independently of PKC phosphorylation of the receptors.
      Arachidonic acid reduced currents through chick alpha7 receptors by a mechanism
      independent of protein kinase activation. In contrast, arachidonic acid
      potentiated currents through rat alpha7, alpha3 beta2, alpha4 beta2, and alpha4
      beta4 receptors, perhaps by the same mechanism as the potentiation observed in
      Torpedo ACh receptors, although it had no effect on rat alpha3 beta4 receptors.
      The results of the present study thus demonstrate that arachidonic acid exerts
      diverse actions on nicotinic ACh receptors by different mechanisms.

PMID- 9630616
TI  - Localization of transferrin binding protein in relation to iron, ferritin, and
      transferrin receptors in the chicken cerebellum.
AB  - We have demonstrated that transferrin binding protein (TfBP), ferritin, and iron,
      are specifically localized in Bergmann glia, while the transferrin receptor is
      confined to Purkinje cells in the chicken cerebellum. The results of this study
      suggest that Bergmann glia have previously undescribed functions related to iron
      regulation such as sequestration of iron and the maintenance of iron homeostasis
      in the cerebellum.

PMID- 9630617
TI  - Chemical lesion of the inferior olive reduces [125I]sarcosine1-angiotensin II
      binding to AT2 receptors in the cerebellar cortex of young rats.
AB  - In young rats, AT2 receptors and AT2 receptor mRNA are discretely localized in
      neurons of the inferior olive, with highest expression in the medial nucleus. We
      previously detected AT2 receptor binding, but not AT2 receptor mRNA, in the
      molecular layer of the cerebellar cortex. To determine whether AT2 receptors are
      expressed in climbing fiber terminals which arise to the molecular layer from the
      inferior olive and innervate Purkinje cells, we chemically destroyed olivary
      neurons of 2-week-old rats by intraperitoneal (i.p.) injection of the neurotoxin
      3-acetylpyridine. Lesions of the inferior olive reduced [125I]Sar1-Ang II binding
      to AT2 receptors and AT2 receptor mRNA levels in this area by 50%, and produced a
      similar decrease in AT2 receptor binding in the molecular layer of the cerebellar
      cortex. The extent of binding reduction was similar 3 days and 7 days after the
      lesion. 3-Acetylpyridine lesions did not change [125I]Sar1-Ang II binding to AT1
      receptors in the molecular layer of the cerebellar cortex or AT1 receptor mRNA
      levels in Purkinje cells. AT2 receptor binding and AT2 receptor mRNA levels in
      the deep cerebellar nuclei were also not affected by 3-acetylpyridine. Our
      results support the hypothesis that AT2 receptors are produced by inferior
      olivary neurons and transported through climbing fibers to the molecular layer of
      the cerebellar cortex. The high expression of AT2 receptors in the inferior
      olivary-cerebellar pathway during a crucial time in postnatal development of
      climbing fiber-Purkinje cell connectivity suggest a role of AT2 receptors in the
      development of this pathway.

PMID- 9630618
TI  - Bovine seminal platelet-activating factor acetylhydrolase: association properties
      in seminal plasma and with lipoproteins.
AB  - The enzyme responsible for most of the phospholipase A2 (PLA2) activity present
      in bovine seminal plasma was recently purified to homogeneity. Sequencing
      revealed that the enzyme is also a platelet-activating factor acetylhydrolase
      (PAF-AH) of the serum type with kinetic properties generally similar to its serum
      homologue. In the present work, we have attempted to clarify its physiological
      function by studying its association properties in seminal plasma. As was
      observed previously for its PLA2 activity, its PAF-AH activity was also inhibited
      by the major proteins of bovine seminal plasma (BSP proteins). Sequential
      dilution experiments as well as centrifuging semen on Percoll did not reveal
      detectable association of PAF-AH with spermatozoa. Neither did the enzyme
      interact with lipid particles reported to be present in bovine seminal plasma.
      The purified PAF-AH, however, did display lipoprotein association properties in
      vitro similar to those demonstrated by the serum enzyme in vivo. At pH 7.4, it
      could associate with both low density lipoproteins and very low density
      lipoproteins but not with high density lipoproteins. Overall the data presented
      here indicate that the enzyme is strongly inactivated as a PAF-AH in seminal
      plasma and that it does not associate with lipid particles or spermatozoa.

PMID- 9630619
TI  - Structure and sequence of human M/NEI (monocyte/neutrophil elastase inhibitor),
      an Ov-serpin family gene.
AB  - Human monocyte/neutrophil Elastase Inhibitor (M/NEI) is a proteinase inhibitor
      that regulates the activity of the neutrophil proteases: elastase, cathepsin G
      and proteinase-3. Evidence indicates that M/NEI belongs to the Ov-serpin family
      (ovalbumin-related serpins), functionally diverse proteins with shared structural
      features. Recombinant lambda phage clones were isolated that encompass the full
      length M/NEI gene plus upstream and downstream regions. The gene, 9.5kb long,
      consists of 7 exons and 6 introns. The 5' transcription start site identified by
      primer extension corresponds to a 60bp exon 1; the translation start site is in
      exon 2. Southern blots established a gene copy number of one. The 3' untranslated
      region (UTR) contains three AATAAA/AATTAA sites; these were shown to function as
      alternative polyadenylation signals. A 14-nucleotide upstream motif including the
      atypical TATA box TATAAGAG otherwise occurs only twice in GenBank, in the genes
      encoding neutrophil elastase and proteinase-3, target proteases inhibited by
      M/NEI. Comparison of M/NEI and previously characterized related genes strongly
      suggests that all Ov-serpins, despite a difference in chromosomal localization
      and exon number, nonetheless, share a common basic gene structure.

PMID- 9630620
TI  - Iron transport in K562 cells: a kinetic study using native gel electrophoresis
      and 59Fe autoradiography.
AB  - The exact mechanisms of iron transport from endosomes to the target iron
      containing cellular proteins are currently unknown. To investigate this problem,
      we used the gradient gel electrophoresis and the sensitive detection of 59Fe by
      autoradiography to detect separate cellular iron compounds and their iron
      kinetics. Cells of human leukemic line K562 were labeled with [59Fe]transferrin
      for 30-600 s and cellular iron compounds in cell lysates were analyzed by native
      electrophoretic separation followed by 59Fe autoradiography. Starting with the
      first 30 s of iron uptake, iron was detectable in a large membrane bound protein
      complex (Band I) and in ferritin. Significant amounts of iron were also found in
      labile iron compound(s) with the molecular weight larger than 5000 as judged by
      ultrafiltration. Iron kinetics in these compartments was studied. Band I was the
      only compound with the kinetic properties of an intermediate. Transferrin,
      transferrin receptor and additional proteins of the approximate molecular weights
      of 130000, 66000 and 49000 were found to be present in Band I. The labile iron
      compounds and ferritin behaved kinetically as end products. No evidence for low
      molecular weight transport intermediates was found. These results suggest that
      intracellular iron transport is highly compartmentalized, that iron released from
      endosomal transferrin passes to its cellular targets in a direct contact with the
      endosomal membrane complex assigned as Band I. The nature of the labile iron pool
      and its susceptibility to iron chelation is discussed.

PMID- 9630621
TI  - Intestinal NF-kappaB is activated, mainly as p50 homodimers, by platelet
      activating factor.
AB  - NF-kappaB, a transcription factor, upregulates gene transcription of many
      inflammatory mediators. Here, we examined the activity of NF-kappaB in the rat
      small intestine, and how it may be affected by platelet-activating factor (PAF),
      an important mediator for intestinal injury and inflammation. Ileal nuclear
      extracts from sham-operated and PAF (1.5 microg/kg)-injected rats were prepared
      for the assessment of NF-kappaB DNA-binding activity, and the identification of
      NF-kappaB subunits. The experiment was also performed on neutrophil-depleted rats
      to examine whether the PAF effect is neutrophil-dependent. Cellular NF-kappaB was
      localized by immunohistochemistry. We found that: (a) NF-kappaB is constitutively
      active in rat small intestine; (b) PAF at a dose below that causing shock and
      bowel necrosis enhances DNA-binding activity of NF-kappaB within 30 min after
      injection; activated NF-kappaB contains predominantly p50 subunits; (c)
      immunohistochemistry showed that PAF induced translocation of p50 into the
      nucleus of cells of the lamina propria, as well as of the epithelium; and (d) the
      effect of PAF is abrogated by neutrophil depletion, suggesting a role of
      neutrophils in NF-kappaB activation. Our study suggests that NF-kappaB is weakly
      active constitutively in the intestine, and inflammatory stimuli such as PAF
      activate NF-kappaB and enhance its DNA-binding activity in the intestine, which
      contains predominantly p50 subunits.

PMID- 9630622
TI  - Novel fluorescence membrane fusion assays reveal GTP-dependent fusogenic
      properties of outer mitochondrial membrane-derived proteins.
AB  - We have shown that fusion of small unilamellar vesicles (SUV) with outer
      mitochondrial membranes occurs at physiological pH [Cortese et al., 1991, J. Cell
      Biol., Vol. 113, 1331-1340]. The proteins driving this process could be involved
      in mitochondrial membrane fusion, which is presently poorly understood. In this
      study, we release from rat liver mitochondria a soluble protein fraction (SF)
      that increases fusion at neutral pH measured by membrane fusion assays (MFAs).
      Since this fusogenic activity was specifically enhanced by GTP, we separate SF by
      GTP affinity chromatography into: i) a flow-through subfraction (G1) containing
      numerous proteins with low GTP affinity; and ii) a subfraction (G2) which may
      contain GTP-binding proteins. A novel array of MFAs is developed to study the
      fusogenic properties of these fractions, measuring the merging of membranes
      (membrane-mixing) or the mixing of intravesicular aqueous contents (content
      mixing). The MFAs use: a) SUV/large unilamellar vesicles, lacking mitochondrial
      membranes; b) SUV/mitochondria, reconstituting membrane-mitochondrial
      interactions; and c) mitochondria/mitochondria, mimicking mitochondrial fusion.
      The results indicate that: i) G1 contains GTP-independent, in vitro fusogenic
      proteins that are not sufficient to induce mitochondrial fusion; and ii) G2
      contains GTP-dependent proteins that stimulate mitochondrial fusion at neutral
      pH. The MFAs described here could be used to monitor the isolation of active
      proteins from these subfractions and to define the mechanism of
      intermitochondrial membrane fusion.

PMID- 9630623
TI  - Calcium-dependent and ATP-sensitive potassium channels and the 'permissive'
      function of cyclic GMP in hypercapnia-induced pial arteriolar relaxation.
AB  - The conclusion that cyclic 3'-5 guanosine monophosphate (cGMP) functions in a
      'permissive' manner in promoting cerebrovasodilation during hypercapnia was based
      on findings showing that the nitric oxide synthase (NOS) inhibitor-induced
      repression of the CO2 response could be reversed upon addition of exogenous cGMP.
      We hypothesized that the action of cGMP revealed in those studies does not define
      its normal role in hypercapnic cerebral vasodilation, but rather is a unique
      function of the artificial situation of NOS inhibition coupled with cGMP
      repletion. Thus, although CO2 reactivity may be the same in normal versus cGMP
      repleted animals, the factors contributing to that response may differ. To test
      that possibility, the effects of calcium-dependent (KCa) or ATP-sensitive (KATP)
      potassium channel blockers on pial arteriolar CO2 reactivity, in vivo, were
      evaluated in the presence and absence of NOS inhibition plus administration of a
      cGMP analogue. Pial arteriolar diameter changes in hypercapnia were measured in
      three principal groups of anesthetized rats: (I) KCa channel-inhibited (via
      iberiotoxin); (II) KATP channel-inhibited (via glibenclamide); and (III)
      controls. Group I and II rats were further divided into: (a) those treated with
      the neuronal NOS (nNOS) inhibitor, 7-nitroindazole (7-NI), followed by successive
      suffusions of the cGMP analogue, 8-bromo-cGMP (8Br-cGMP) and 8Br-cGMP+K-channel
      blocker; and (b) rats where 7-NI and 8Br-cGMP applications were omitted. Group
      III rats were divided into time and 8Br-cGMP controls. Hypercapnia (PCO2
      congruent with60 mmHg, 3 min)-induced dilations were reduced by 70-80% following
      7-NI and restored by 8Br-cGMP. That restoration was reversed by both K-channel
      blockers. In the absence of 7-NI and exogenous cGMP, CO2 reactivity was
      unaffected by K-channel inhibition. These findings confirmed that nNOS-derived NO
      is critically important to the hypercapnic reactivity of cerebral arterioles, and
      that cGMP repletion, following NOS inhibition, could restore CO2 reactivity. The
      observation that KCa and KATP channel blockade did not alter CO2 reactivity under
      baseline conditions, but attenuated CO2 reactivity only in the presence nNOS
      inhibition (and cGMP repletion), suggests that multiple, redundant, and
      interactive mechanisms participate in CO2-induced vasodilation. These results
      also imply that current strategies for revealing permissive actions of cGMP (or
      NO) may need to be re-evaluated.

PMID- 9630624
TI  - Prostaglandin I2 analog enhances the expression of urokinase-type plasminogen
      activator and wound healing in cultured human fibroblast.
AB  - This study examines the effects of prostaglandin I2 (PGI2) on urokinase-type
      plasminogen activator (uPA) production and wound healing by human fibroblasts.
      Employing fibrin autography, it was found that beraprost sodium, a stable PGI2
      analog, enhanced the fibrinolytic activity in media conditioned by human
      fibroblasts, TIG-3-20 cells. Fibrin zymography, ELISA, and Northern blot analysis
      confirmed that the enhanced activity was caused by an increase in uPA synthesis
      and secretion and a decrease in type-1 plasminogen activator inhibitor. While
      cycloheximide and 2',5'-dideoxyadenosine, an adenylate cyclase inhibitor,
      suppressed the effect of PGI2, dibutyryl cyclic AMP increased the fibrinolytic
      activity and uPA mRNA. These findings indicate that PGI2 promotes uPA production
      in TIG-3-20 cells via direct stimulation of the cyclic AMP intracellular pathway.
      A similar effect was observed in two other fibroblast cell lines, TIG-7-20 and
      TIG-7-30. Although PGI2 itself did not affect cellular proliferation, it promoted
      in vitro repopulation of the denuded area in a wounded monolayer. These
      observations suggest that PGI2 can stimulate wound healing through the enhanced
      production of uPA.

PMID- 9630625
TI  - Chromosomal mapping and expression of the human B120 gene.
AB  - We previously reported a novel human cDNA, designated B120, containing a CAG
      repeat length polymorphism and many repeat units, loosely identified as YXQQP
      which is found in several human RNA binding proteins. In the present study, the
      B120 gene was mapped to human chromosome 1p35-36.1 by fluorescence in situ
      hybridization (FISH). Several human disorders, including that of Schnyder
      crystalline corneal dystrophy, have been mapped to this region by genetic
      linkage. Schnyder crystalline corneal dystrophy is thought to be a primary
      abnormality of corneal lipid metabolism, resulting in opacification secondary to
      lipid accumulation. In order to examine the function of B120, we introduced B120
      cDNA with an expression vector into various cell lines including Cos1, C3H/10T1/2
      and NIH/3T3 cells. These transfected cells exhibited small cytoplasmic spherical
      bodies. The cytoplasmic bodies appeared to be fat droplets on electron microscopy
      and histochemical staining. These findings suggested that B120 gene expression is
      associated with lipid metabolism, and that overexpression of B120 may result in
      lipid deposition in various cells, including those of fibroblastic cell lines.
      Since the cornea is composed of fibroblastic cells, overfunction of B120 could be
      related to the pathogenesis of Schnyder crystalline corneal dystrophy.

PMID- 9630626
TI  - Inhibition of 14-kDa PLA2 by 2-acylamino-alkylphospholipids: the influence of
      amide acidity.
AB  - 2-Acylamino-alkyl phospholipids are potent competitive inhibitors of 14-kDa
      phospholipases A2 (e.g., human nonpancreatic secretory PLA2). As concluded from X
      ray studies the amide hydrogen of these inhibitors forms a hydrogen bond to His
      48 in the active site of the enzyme. We investigated the quantitative
      contribution of this hydrogen bond to inhibition using especially designed
      inhibitors that bear different acyl chains with and without electron withdrawing
      or donating substituents, thus differing in amide acidity. Relative free
      enthalpies DeltaDeltaG of enzyme-inhibitor complex formations were calculated
      from Xi(50) values determined by pH-stat titration using a mixed micelles assay
      and PLA2 from Naja mocambique mocambique. A quantitative relationship between
      amide acidity and DeltaDeltaG values is presented. Comparison of isoacidic and
      isosteric inhibitors reveals that (i) the hydrogen bond of the amide proton to
      His-48 is crucial for strong PLA2 inhibition, (ii) regardless of the headgroup
      unsubstituted N-acyl groups result in optimal amide acidity for PLA2 inhibition
      and (iii) the exceptionally strong inhibition by acetamides and the isosteric
      fluoroacetamides is due to an additional steric effect.

PMID- 9630627
TI  - Modifications in protein binding to upstream sequences of the sea urchin
      cytoplasmic actin gene CyIIa in comparison to its linked neighbors, CyI and
      CyIIb.
AB  - The sequences corresponding to regions upstream of the ATG and transcription
      start site of the CyIIa cytoplasmic actin gene of the sea urchin
      Strongylocentrotus purpuratus were determined and compared to the genomically
      linked CyI and CyIIb actin genes. Sites of protein-DNA interaction in the CyIIa
      upstream sequences were identified by DNase I footprinting. The similarity
      between CyIIa and CyI (and CyIIb) upstream sequences was limited and included a
      consensus octamer sequence, serum response element (SRE) and some short sequences
      within the proximal promoter region. The octamer sequence was found to bind
      protein. A single DNase I hypersensitive site was detected within the SRE and to
      two flanking nucleotides, but otherwise, the SRE did not appear to be protected.
      This is in contrast to strong protein binding to the CyIIb SRE. A region in the
      CyIIa gene with limited identity to the functionally significant protein binding
      site D in CyI also did not bind protein. Four additional sites of protein-DNA
      interaction were identified in CyIIa upstream sequences. One of these is similar
      to a protein binding site previously located in the CyI upstream sequences,
      whereas the others appear to be unique. These data indicate that the CyIIa
      upstream sequences differ extensively from those of CyI. The pattern of CyIIa
      expression is likely a consequence of these alternations in DNA sequence and
      protein-DNA interactions.

PMID- 9630628
TI  - Development of spontaneous seizures over extended electrical kindling. I.
      Electrographic, behavioral, and transfer kindling correlates.
AB  - The present study was aimed at evaluating an extended kindling model of
      spontaneous epilepsy. Behavioral and electrographic responses to repeated
      kindling of either the perforant path or amygdala were monitored for up to 300
      trials. Kindling initially led to generalized convulsions equivalent to the level
      5 seizure on the rating scale developed by Racine. The evoked seizures became
      progressively more complex with additional kindling, which was described by a 10
      stage classification system. The highest stage (stage 10) was achieved when the
      kindling stimulation evoked two or more bouts of level 5 seizures combined with
      running and jumping fits. These more complex seizures developed over the course
      of amygdala, but not perforant path kindling. Electrographic seizures from both
      the amygdala and dentate gyrus increased in duration and amplitude during the
      early phase of kindling, but did not correlate with motor seizure development
      beyond level 5. During the late phase of kindling, the dentate gyrus
      afterdischarge amplitude decreased and became dissociated from the behavioral
      seizures. Manifestations of spontaneously recurring seizures were seen in the
      majority of animals, but spontaneous seizures of level 4 or greater were observed
      in only five rats. The second part of this study examined kindling transfer
      effects, the efficacy of kindling a new site after the completion of the initial
      (in this case extended) kindling protocol. The effect depended on both primary
      and secondary site location. When the amygdala served as primary site, perforant
      path transfer was complete in some animals but absent in others. No transfer
      occurred in the opposite direction, from the perforant path to the amygdala.
      Finally, transfer effects in the dentate gyrus, which was tested as tertiary
      site, were complete. Previous studies have found weaker transfer effects in the
      dentate when kindling to the standard stage 5 level.

PMID- 9630629
TI  - Sequence-related behaviour of transmembrane domains from class I receptor
      tyrosine kinases.
AB  - 2H NMR spectroscopy and freeze-fracture electron microscopy were used to compare
      the transmembrane domains of two Class I protein receptor tyrosine kinases (the
      EGF receptor and Neu/erbB-2) regarding overall behaviour in fluid lipid bilayer
      membranes. The 34-residue peptide, EGFRtm, was synthesised to contain the 23
      amino acid hydrophobic stretch (Ile622 to Met644) thought to span the membrane of
      the human EGF receptor, plus the first 10 amino acids (Arg645 to Thr654) of the
      cytoplasmic domain. Deuterium probes replaced selected 1H nuclei at sites
      corresponding to Ala623, Met644, and Val650. The 38-residue peptide, Neutm, was
      synthesised having the 21 residue hydrophobic stretch (Ile660 to Ile680)
      calculated to span the membrane in rat Neu/erbB-2, plus residues Lys681 to Thr691
      of the contiguous cytoplasmic domain. Deuterium probes replaced selected 1H
      nuclei at Ala661, Leu667, and Val676. A third peptide, Neutm*, was also prepared,
      corresponding to the transmembrane domain of a constitutively-activating Neu/erbB
      2 transformant in which Val664 is replaced by Glu: it was deuterated in a manner
      identical to Neutm. Peptides were studied by 2H NMR spectroscopy at 1 mol% and 6
      mol% in unsonicated fluid bilayers of 1-palmitoyl-2-oleoylphosphatidylcholine
      (POPC) and in POPC containing 33 mol% cholesterol, over the range 12 degrees to
      65 degreesC. Overall motion was found to be different for each of the three
      peptides under a given set of conditions. EGFRtm spectra were characteristic of
      axially symmetric motion in membranes of POPC alone, and in POPC/cholesterol at
      35 degreesC and above. In contrast, spectra of the transmembrane peptides, Neutm
      and Neutm*, were characteristic of significantly axially asymmetric motion under
      all conditions studied (and regardless of sample preparation method). Addition of
      33% cholesterol to membranes was accompanied by spectral changes consistent with
      increased formation of peptide dimers/oligomers in all cases. The transformant
      peptide, Neutm*, showed greater spectral evidence of immobilisation than did the
      wild type - probably reflecting a greater tendency to form large oligomers.
      Sequence-related details within the transmembrane domains of Class I receptor
      tyrosine kinases appear to exert important control over their associations within
      membranes. Freeze-fracture electron microscopy of the NMR samples demonstrated
      their liposomal nature. Peptide-related intramembranous particles (IMPs) were
      present which likely represent oligomers of the transmembrane peptide. IMP size
      and distribution were similar under a given set of conditions for all three
      peptides, suggesting that the differences seen by NMR spectroscopy reflect
      structures smaller than the 2 nm resolution limit of freeze-fracture EM and
      peptide relationships within its 20 nm accuracy of identifying lateral position.

PMID- 9630630
TI  - The tight association of protein kinase CK2 with plasma membranes is mediated by
      a specific domain of its regulatory beta-subunit.
AB  - Previous immunocytochemical studies have shown that protein kinase CK2 is mostly
      detected both in the cytoplasm and the nucleus of most cells. In the present
      study, CK2 was detected in highly purified plasma membrane preparations from rat
      liver. The protein kinase could be released from the membranes by high salt
      extraction (>1 M NaCl). Plasma membranes prepared from SF9 insect cells
      expressing the alpha- and beta-subunits of CK2 also contained a significant
      amount of oligomeric CK2. Furthermore, it was demonstrated in this cell system as
      well as in rat liver plasma membranes, that the beta-subunit of the kinase is the
      targeting subunit which mediates the tight association of the enzyme to plasma
      membrane components. Binding studies using membranes and recombinant proteins
      corresponding to different regions of the beta-subunit suggest that a functional
      domain previously shown to be involved in the binding of polyamines may also
      participate to the binding of CK2 to membranes. Modification of membranes by
      trypsin and phospholipases indicated that the binding process may require both
      membrane protein(s) and phospholipids. Interestingly, it was observed that the
      amount of membrane-bound CK2 in liver of embryos and new born rats increases
      dramatically after birth and persists during the postnatal stages of development.

PMID- 9630631
TI  - Electrospray ionization tandem mass spectrometric analysis of sulfatide.
      Determination of fragmentation patterns and characterization of molecular species
      expressed in brain and in pancreatic islets.
AB  - The sphingolipid sulfatide is a component of myelin and some non-neuronal cells.
      Antibodies to sulfatide occur in some patients with autoimmune neuropathies and
      in patients with insulin-dependent diabetes mellitus (IDDM) caused by immunologic
      destruction of insulin-secreting pancreatic islet beta-cells. Distinct sulfatide
      molecular species may differ in immunogenicity, and facile means to identify
      sulfatide species in islets and other tissues obtainable in only small amounts
      could be useful. Electrospray ionization mass spectrometry (ESI/MS) permits
      structural determination of small quantities of phospholipids and is applied here
      to sulfatide analysis. We find that sulfatide standards are readily analyzed by
      negative ion ESI/MS, and tandem mass spectra of individual species exhibit some
      ions common to all species and other ions that reflect distinct fatty acid
      substituents in different sulfatide molecules. A signature ion cluster resulting
      from cleavage directed by the alpha-hydroxy group of sulfatide species with a
      hydroxylated fatty acid substituent identifies such species. Sulfatide profiles
      in tissue lipid extracts can be obtained by ESI/MS/MS scanning for common
      sulfatide ions and for ions reflecting fatty acid substituents. Islets are
      demonstrated to contain sulfatide and to exhibit a profile of species different
      from that of brain.

PMID- 9630632
TI  - Characterization of the human mitochondrial aconitase gene (ACO2).
AB  - We have cloned and characterized the ACO2 gene on human chromosome 22q13, which
      encodes the essential iron-dependent metabolic enzyme mitochondrial aconitase. We
      determined that the ACO2 gene comprises 18 translated exons distributed over
      approximately 35 kilobasepairs (kbp) of DNA. We have shown that the ACO2 mRNA is
      2.7kb in length and is expressed ubiquitously, and we can detect multiple
      isoforms of the ACO2 protein. As others had reported the existence of
      biochemically active electrophoretic variants of mitochondrial aconitase, we
      wished to find common ACO2 gene allozymes, functional polymorphisms that might be
      associated with susceptibility to human genetic diseases. We looked for ACO2
      allozymes by DNA sequencing and genotyping in a population of 217 subjects, many
      of which had idiopathic Parkinson's disease (IPD). We studied patients with IPD
      because this movement disorder is thought to arise from defects in neuronal iron
      and energy metabolism, two properties with which aconitase is involved.
      Furthermore, reports of associations between alleles of the CYP2D6 locus (nearby
      on 22q13) and IPD, although inconsistent, indicated that an IPD susceptibility
      locus might be in strong linkage disequilibrium with CYP2D6. We found three
      functionally silent single nucleotide polymorphisms (SNPs) present in transcribed
      sequences that exist in similar frequencies in IPD patients and healthy controls.
      These ACO2 SNPs are in linkage disequilibrium with each other, providing evidence
      for distinct ACO2 haplotypes. We have, as yet, not detected polymorphisms that
      would lead to ACO2 allozymes, nor have we observed differences in ACO2 isoform
      prevalence or distribution in our population of IPD patients and controls. We
      conclude it is unlikely that polymorphism in the ACO2 gene or post-translational
      modification of the enzyme predispose to IPD.

PMID- 9630633
TI  - Chronic ethanol administration down-regulates cannabinoid receptors in mouse
      brain synaptic plasma membrane.
AB  - The effects of chronic ethanol (EtOH) consumption on the central nervous system
      may be related in part to its action on biological membranes by altering various
      receptor functions. In the current study, we examined the effects of chronic EtOH
      (4 day inhalation) on cannabinoid receptors (CB1) labeled with [3H]CP55,940 in
      synaptic plasma membranes (SPM) isolated from mouse brain. Our results indicate
      the presence of a high level of CB1 receptors in controls (Bmax=12.0+/-0.3 pmol
      mg-1 protein) which decreased significantly (-58%) in SPM from mouse brain
      chronically exposed to EtOH. This effect occurs without any changes in the
      receptor affinity (Kd=2. 3+/-0.3 nM for control and 2.9+/-0.3 nM for EtOH group,
      P>0.05). Dissociation kinetic results showed a dissociation rate constant (K-1)
      of 0.09+/-0.01 min-1 for control and this dissociation rate constant decreased
      significantly in the chronic EtOH treated mice brain (0.05+/-0.01 min-1, P<0.05).
      The competition studies with anandamide resulted in a substantial decrease in
      [3H]CP55,940 binding in both the control and EtOH group, with a decrease (P<0.05)
      in the Ki values in the SPM of chronic EtOH exposed mice. Hill transformation
      analysis showed an nH close to one in control (0. 92+/-0.01). This did not change
      significantly after chronic EtOH (0. 95+/-0.01) administration, which indicates
      the existence of a single class of receptor for [3H]CP55,940 binding in SPM from
      control and EtOH treated mice. The observed down-regulation of CB1 receptors by
      chronic EtOH may indicate the involvement of cannabinoid receptors in EtOH
      tolerance and dependence.

PMID- 9630634
TI  - Thiamine transport in human placental brush border membrane vesicles.
AB  - Pathways for transport of thiamine by the human placental epithelium were
      investigated using brush border membrane vesicles isolated by divalent cation
      precipitation. The presence of thiamine transport mechanisms mediating Na+
      thiamine cotransport, proton/thiamine exchange and facilitated diffusion was
      assessed from [3H]-thiamine tracer flux measurements. The magnitude of
      intravesicular thiamine accumulation was unaffected by the imposition of an
      inwardly directed sodium gradient suggesting an absence of a mechanism mediating
      brush border membrane Na+-thiamine cotransport. Intravesicular thiamine
      accumulation was indistinguishable when measured in the presence and absence of
      conditions favoring the development of an inside-negative, potassium diffusion
      potential. The observed absence of conductive thiamine uptake suggests the
      absence of a mechanism mediating facilitated diffusion of thiamine in placental
      brush border membrane. The imposition of an inside-acid pH gradient was observed
      to induce concentrative accumulation of thiamine to levels exceeding equilibrium,
      suggesting the presence of a placental brush border membrane proton/thiamine
      exchange mechanism. Protonophore- induced dissipation of an imposed inside-acid
      pH gradient in the absence of membrane potential was observed to abolish
      concentrative accumulation of thiamine, suggesting a direct chemical coupling of
      protons and thiamine via a mediated exchange mechanism. Consistent with the
      functional properties expected for a mechanism mediating thiamine transport by
      organic cation exchange, the rate and magnitude of intravesicular [3H]-thiamine
      accumulation was increased when measured in the presence compared to the absence
      of an outwardly directed thiamine concentration gradient. Substrate specificity
      studies of the proton/thiamine exchange mechanism suggest that the amine at
      position four of the pyrimidine ring, but not the hydroxyethyl side chain or an
      unmodified thiazolium ring, is an important chemical determinant for interaction
      with the transporter substrate binding site(s). Substrate specificity studies
      further suggest the possible presence of three separate organic cation exchange
      mechanisms mediating transport of thiamine, guanidine and MIA across placental
      brush border membrane.

PMID- 9630635
TI  - TNF-induced modulations of phospholipid metabolism in human breast cancer cells.
AB  - Tumor necrosis factor alpha (TNF) is a cytokine that is cytocidal for certain
      tumor cells and induces necrotic and apoptotic forms of cell death. Flow
      cytometry and transmission electron microscopy analysis demonstrated that in
      human breast cancer cells (MCF7) TNF induces cell cycle arrest in G0+G1/S,
      accompanied by apoptosis. 31P and 13C NMR spectroscopy was applied to study
      cellular metabolism of MCF7 cells during TNF-induced signal to apoptosis.
      Deuterated choline and 2H NMR spectroscopy were utilized to monitor the kinetics
      of the rate limiting reactions in phosphocholine metabolism. The NMR measurements
      revealed that immediately after administration of TNF, choline transport was
      inhibited by 52+/-6%. Later (approximately 15 h), the activity of
      phosphocholine:cytidine triphosphate cytidylyltransferase, a key enzyme in the
      biosynthesis of phosphatidylcholine, was enhanced two-fold. These two opposing
      changes led to a decrease in the level of phosphocholine. Throughout these
      changes the energetic state of the cells, determined by the level of nucleoside
      triphosphates and the rate of glucose metabolism via glycolysis, remained
      constant. The results indicate that TNF specifically modulates the kinetics of
      membrane-bound enzymes of the rate determining steps in phosphatidylcholine
      biosynthesis, possibly as part of early events involved in apoptosis.

PMID- 9630636
TI  - The presence of transthyretin in rat ependymal cells is due to endocytosis and
      not synthesis.
AB  - The presence and synthesis of transthyretin, a major carrier protein of thyroxine
      in rat cerebrospinal fluid, was investigated in choroid plexus epithelial cells
      and ependymal cells by immunocytochemistry, in situ hybridization, and analysis
      by Northern and Western blot using a specific oligonucleotide probe and a
      specific polyclonal antibody to transthyretin. Choroid plexus epithelial cells
      expressed transthyretin at high levels in developing rat cerebral hemispheres and
      in cultured cells. These cells secreted transthyretin into the cerebrospinal
      fluid. In the developing rat brain transthyretin was present in the cytoplasm of
      ependymal cells, in vesicles in contact with the apical membrane and in cilia. In
      ependymal cell cultures this protein was particularly abundant in the cilia of
      these cells. In contrast, ependymal cells did not synthesize transthyretin. It is
      postulated that transthyretin is transported to ependymal cells from the
      cerebrospinal fluid by endocytosis.

PMID- 9630639
TI  - Proceedings of the workshop entitled 'Sources, effects, and potential hazards of
      genotoxic complex mixtures in the Environment' . 28th annual meeting of the
      environmental mutagen society, april 20, 1997, minneapolis, MN 

PMID- 9630637
TI  - Gene expression and activity of specific opioid-degrading enzymes in different
      brain regions of the AA and ANA lines of rats.
AB  - There is increasing evidence that alcoholism runs in families suggesting that
      genetic factors may play a role. In support of this hypothesis, the alcohol
      preferring (AA) and the alcohol-avoiding (ANA) rat lines have been developed
      through selective outbreeding. Numerous studies indicate that the endogenous
      opioid system may be involved in controlling ethanol consumption. Changes in
      opioid peptides and opioid receptors have been described after ethanol intake.
      But, the influence of ethanol on peptidolytic degradation of opioid peptides has
      been largely ignored, although the peptidase-mediated metabolism of neuropeptides
      is known as an important regulatory site of peptidergic transmission. Neutral
      endopeptidase 24.11 (NEP) and angiotensin-converting enzyme (ACE) degrade
      neuropeptides, including enkephalin and are expressed in the brain. Furthermore,
      a good correspondence between the regional distribution of NEP and opioid
      receptors in rat brain has already been reported pointing to a possible role of
      NEP in regulating opioid peptides. For both enzymes studied, the gene expression
      pattern was found to be in good agreement with the corresponding enzyme
      activities in the brain regions investigated, showing the highest levels for both
      specific mRNAs and enzyme activities in the striatum. Differences in both
      measured parameters were detected in distinct brain regions of AA and ANA rats.
      Furthermore, in some brain regions discrepancies between ACE and NEP mRNA levels
      and the corresponding enzyme activities were observed. For example, in olfactory
      bulb and striatum such discrepancies were found for both enzymes studied. In
      tegmentum/colliculi a higher NEP gene expression in AA rats was associated with a
      higher NEP enzyme activity compared to the amounts found in ANA rats.

PMID- 9630641
TI  - Temperature change of the lamellar structure of DPPC/disaccharide/water systems
      with low water content.
AB  - Temperature change in l-alpha-dipalmitoyl phosphatidylcholine (DPPC)/disaccharide
      systems with low water content (less than 8 wt. %) was investigated using X-ray
      diffraction within a range of two transition temperatures. X-ray diffraction
      above the higher transition temperature showed a broad symmetric peak, indicating
      the Lalpha phase. Below the higher transition temperature, two overlapping
      diffraction peaks were observed. After peak separation, temperature change in
      these systems was analyzed using peak parameters of the two peaks. Peak
      parameters of the lower angle peak changed continuously up to and above the
      higher transition temperature, suggesting the systems to be in a liquid crystal
      phase below the higher transition temperature. Fourier-transform infrared (FT-IR)
      spectra of the DPPC/trehalose system with 5.5 wt.% water showed the wave number
      of asymmetric stretching of phosphate groups to change at the lower transition
      temperature and that of symmetric stretching of CH2 groups, to change between the
      lower and higher transition temperatures. Thus, below the lower transition
      temperature, the system is shown to be in a gel phase. Conformational change in
      phosphate groups occurred at the lower transition temperature. Within the lower
      and higher transition temperatures, two phases were found to coexist and
      transition from the gel phase to Lalpha phase to occur continuously. Above the
      higher transition temperature, the system is in the Lalpha phase.

PMID- 9630644
TI  - Corrigendum to: 'Structure and expression of the chicken calmodulin I gene'

PMID- 9630645
TI  - Corrigendum to: 'Identification and characterization of a mouse homologue of the
      spinal muscular atrophy-determining gene, survival motor neuron'

PMID- 9630643
TI  - The genotoxic hazards of domestic wastes in surface waters.
AB  - Despite the noteworthy genotoxic potency of many industrial wastewaters, the
      genotoxic hazard posed to the downstream ecosystem and its associated biota will
      be determined by genotoxic loading. Municipal wastewaters, although ranking low
      in potency, can achieve loading values that are several orders of magnitude
      greater than those of most industries. Although these wastewaters are generally
      mixtures of wastes from several different sources, the volumetric proportion of
      the daily discharge that is of industrial origin rarely exceeds 30%. Genotoxicity
      calculations for the Montreal Urban Community (MUC) municipal wastewater
      treatment facility indicate that over 90% of the genotoxic loading (31.1 kg
      benzo(a)pyrene equivalents per day) is nonindustrial in origin. Moreover, a mass
      balance of surface water genotoxicity for St. Lawrence river at Montreal
      indicates that over 85% of the total contributions from the Montreal region are
      nonindustrial in origin. Additional calculations for the Great Lakes, and other
      rivers throughout the world, provide further support of a strong relationship
      between surface water genotoxicity and population. Despite some information about
      physical/chemical properties, the identity of the putative genotoxins in
      municipal wastewaters and surface waters remains a mystery. Likely candidates
      include potent genotoxins, such as N-nitroso compounds and aromatic amines, known
      to be present in human sanitary wastes, as well as genotoxic PAHs known to be
      present in many municipal wastewaters. Calculations based on literature data
      indicate that human sanitary wastes may be able to account for a substantial
      fraction (4-70%) of the nonindustrial loading from municipal wastewaters. Similar
      calculations suggest that pyrogenic PAHs that enter municipal wastewaters via
      surface runoff can only account for a small fraction (<5%) of the genotoxic
      loading values discussed.

PMID- 9630646
TI  - Effects of EGb 761 on nitric oxide and oxygen free radicals, myocardial damage
      and arrhythmia in ischemia-reperfusion injury in vivo.
AB  - The cardioprotective effects of EGb 761 on the release of nitric oxide (NO), the
      concentration of serum thiobarbituric acid reaction substance (TBARS), the
      activity of creatine kinase (CK) and the incidence of ventricular arrhythmias
      were investigated in myocardial ischemia-reperfusion injury in vivo. Using sodium
      nitrite (NaNO2) as standard source of nitric oxide (NO), we compared the
      correlation coefficients of the three measuring methods used currently in the
      determination of NOFe2+(DETC)2 complex with that of the measuring method
      suggested in this study. The result showed that measuring the whole height of
      three splitting signals is the best linear correlation to the concentration of NO
      comparing with other methods in this system. Using this method, we observed the
      effects of EGb 761 on NOFe2+(DETC)2 complex in myocardial ischemia-reperfusion
      injury in vivo. The hearts of the Wistar rats were subjected to 30 min of
      ischemia and 10 min of reperfusion in vivo. Different doses of EGb 761 (25, 50,
      100, 200 mg/kg i.p.), superoxide dismutase (SOD, 10(4) U/kg), l-arginine (50
      mg/kg i.p.) and nitric oxide synthase (NOS) inhibitor NG-nitro-l-arginine (NNA,
      50 mg/kg i.p.) were administered to the ischemia-reperfusion rats. EGb 761 under
      the dose of 100 mg/kg increased the signal intensity of NOFe2+(DETC)2 complex,
      while EGb 761 at 200 mg/kg showed an effect of decreasing the signal intensity of
      NOFe2+(DETC)2 complex. EGb 761 inhibited the formation of TBARS, the release of
      CK, and mitigated the incidence of ventricular arrhythmias in a dose dependent
      way. Both l-arginine and SOD increased the signal intensity of NOFe2+(DETC)2
      complex and inhibited the formation of TBARS, the leakage of CK and the incidence
      of ventricular arrhythmia. NNA not only had no protective effects on myocardial
      injury, but also increased the incidence of reperfusion-induced arrhythmia. In
      conclusion, EGb 761 has cardiovascular protective effects by means of adjusting
      the level of NO and inhibiting oxygen free radicals induced lipid peroxidation in
      myocardial ischemia-reperfusion injury in vivo.

PMID- 9630647
TI  - A novel organotypic long-term culture of the rat hippocampus on substrate
      integrated multielectrode arrays.
AB  - Spatiotemporally coordinated activity of neural networks is crucial for brain
      functioning. To understand the basis of physiological information processing and
      pathological states, simultaneous multisite long-term recording is a
      prerequisite. In a multidisciplinary approach we developed a novel system of
      organotypically cultured rat hippocampal slices on a planar 60-microelectrode
      array (MEA). This biohybrid system allowed cultivation for 4 weeks. Methods known
      from semiconductor production were employed to fabricate and characterize the
      MEA. Simultaneous extracellular recording of local field potentials (LFPs) and
      spike activity at 60 sites under sterile conditions allowed the analysis of
      network activity with high spatiotemporal resolution. To our knowledge this is
      the first realization of hippocampus cultured organotypically on multi
      microelectrode arrays for simultaneous recording and electrical stimulation. This
      biohybrid system promises to become a powerful tool for drug discovery and for
      the analysis of neural networks, of synaptic plasticity, and of
      pathophysiological conditions such as ischemia and epilepsy.

PMID- 9630648
TI  - Inhibitors of interleukin-1 beta-converting enzyme-family proteases (caspases)
      prevent apoptosis without affecting decreased cellular ability to reduce 3-(4,5
      dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide in cerebellar granule
      neurons.
AB  - We assessed the possible role of interleukin-1beta-converting enzyme-family
      proteases (caspases) in apoptosis in cultured rat cerebellar granule neurons.
      CPP32 (caspase-3)-like protease activity was augmented by low KCl treatment,
      preceding neuronal cell death. Agents such as brain-derived neurotrophic factor
      (BDNF), dibutylyl cAMP, NMDA, actinomycin D, S-adenosyl-L-methionine, and
      spermine prevented apoptosis. For various neuroprotective agents, the degree of
      apoptosis prevention correlated with the prevention of the activation of CPP32
      like protease. Furthermore, Z-Asp-2, 6-dichlorobenzoyloxy-methylketone (Z-Asp-CH2
      DCB), Boc-Asp-fluoromethylketone (Boc-Asp-FMK), and Z-Val-Ala-Asp
      fluoromethylketone (Z-VAD-FMK), which are inhibitors of caspases, also prevented
      apoptosis. In contrast to many other neuroprotective agents, these inhibitors of
      caspases showed little effect on the decrease of cellular 3-[4,5-dimethylthiazol
      2-yl]-2, 5-diphenyltetrazolium bromide (MTT) reduction activity after low KCl
      treatment. The neurons rescued by these inhibitors of caspases during low KCl
      treatment were in a hypoenergic state in their ATP levels and vulnerable to
      subsequent treatment with medium containing high KCl or glutamate which induce an
      influx of Ca2+, but which are less toxic to normal neurons. These results suggest
      that caspase(s) are involved in the apoptosis of cerebellar granule neurons and
      that several agents protect neurons from death by blocking the activation of the
      protease(s). Although several caspase inhibitors examined in this study protect
      neurons from apoptosis, rescued neurons are vulnerable to subsequent stimuli that
      induce necrotic cell death.

PMID- 9630649
TI  - HCO3(-)-dependent ion transport systems and intracellular pH regulation in
      colonocytes from the chick.
AB  - The current study examines the presence of the Na+/HCO3- cotransporter and of the
      Cl-/HCO3- exchanger in chicken colonocytes and their role in cytosolic pH (pHi)
      homeostasis. pHi was measured with 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein
      (BCECF) at 25 degreesC. Basal pHi was 7.16 in HEPES-buffered solutions and 7.06
      in those buffered with HCO3-. Removal of external Cl- increased pHi and Cl-
      reinstatement brought the pHi towards resting values. These Cl--induced pHi
      changes were Na+-independent, inhibited by H2-DIDS and faster in the presence
      than in the absence of HCO3-. Cells recovered from alkaline loads by a mechanism
      that was Cl--dependent, Na+-independent and inhibited by H2-DIDS. This rate of Cl
      -dependent cell acidification decreased as the pHi decreased, with a Hill
      coefficient value close to 4. Removal of external Na+ decreased pHi and
      readdition of Na+ brought pHi towards the control values. The rate of the Na+
      induced changes was not modified by the presence of HCO3- and was prevented by
      EIPA and unaffected by H2-DIDS. In the presence of EIPA cells partially recovered
      from a moderate acid load only when both Na+ and HCO3- were present. The EIPA
      resistant Na+- and bicarbonate-dependent pHi recovery was inhibited by H2-DIDS
      and occurred at equal rates in both Cl--containing and Cl--free solutions. It is
      concluded that in chicken colonocytes bathed in HCO3--buffered solutions, both
      the Na+/H+ exchanger and the Cl-/HCO3- exchanger participate in setting the
      resting pHi value. The latter transporter helps the cells to recover from
      alkaline loads and the first transporter, together with the Na+/HCO3-
      cotransporter, is involved in pHi recovery from an acid load.

PMID- 9630650
TI  - Human lamin B receptor exhibits sterol C14-reductase activity in Saccharomyces
      cerevisiae.
AB  - Lamin B receptor (LBR), a nuclear protein of avian and mammalian cells, contains
      an hydrophobic domain that shares extensive structural similarities with the
      members of the sterol reductase family. To test if the sterol-reductase-like
      domain of LBR could be enzymatically competent, several sterol reductase
      defective strains of Saccharomyces cerevisiae were transformed with a human-LBR
      expressing vector. LBR production did not change the ergosterol biosynthesis
      defect in an erg4 mutant impaired in sterol C24(28) reductase. In contrast, the
      sterol C14 reduction step and ergosterol prototrophy were restored in LBR
      producing erg24 transformants which lack endogenous sterol C14 reductase. To test
      the effects of C14 reductase inhibitors on LBR activity, we constructed EMY54, an
      ergosterol-requiring strain that is devoid of both sterol C8-C7 isomerase and
      sterol C14 reductase activities. EMY54 cells recovered the capability of
      synthesizing ergost-8-en-3beta-ol upon transformation with a vector that
      expressed either yeast sterol C14 reductase or hLBR. In addition, growth in
      sterol-free medium was restored in these transformants. Sterol biosynthesis and
      proliferation of LBR-producing cells were found to be highly susceptible to
      fenpropimorph and tridemorph, but only moderately susceptible to SR 31747. Our
      results strongly suggest that hLBR is a sterol C14 reductase.

PMID- 9630651
TI  - Amyloid precursor protein proteoglycan is increased after brain damage.
AB  - The beta-amyloid peptide (Abeta or A4) is produced by proteolytic cleavage from
      amyloid precursor protein (APP). The progressive cerebral deposition of this
      peptide is one of the most important features of Alzheimer's disease. From the
      study of normal and transfected cells, two APP processing pathways have been
      proposed as physiological alternatives. One of these can produce Abeta or
      amyloidogenic peptides, whereas the second does not. However, it is not
      completely clear how APPs are post-translationally modified, proteolytically
      processed and metabolized in the brain. We report here that APPs also exist as
      proteoglycan, chondroitin-sulfate (ChS). We have identified in normal rat brain a
      complex pool of 8 to 130 kDa ChS-core proteins. The main portion of these
      proteoglycan (PGs) APPs contains complete amyloidogenic sequence, suggesting a
      novel proteolytic processing of APP from the amino-terminal to the transmembrane
      region. This population appears augmented after brain damage. These findings may
      have significant implications in understanding the initial deposition and
      kinetics of amyloid aggregation in a pathological situation like Alzheimer's
      disease.

PMID- 9630652
TI  - Genotoxicity of industrial wastes and effluents.
AB  - In excess of several million pounds of genotoxic and/or carcinogenic industrial
      wastes are released into the U.S. environment each year. Chemical
      characterization of these waste materials can rarely provide an adequate
      assessment of their genotoxicity and potential hazard. Bioassays do not require
      prior information about chemical composition and can effectively assess the
      genotoxicity of complex waste materials. The most commonly used genotoxicity
      assay has been the Salmonella mutagenicity assay. Results with this system have
      shown that the genotoxic potency of industrial wastes can vary over 10 orders of
      magnitude, from virtually nondetectable to highly potent. Industries employing
      similar industrial processes generally release wastes of similar potency.
      Extremely high potency wastes include those from furazolidone and nitrofurfural
      production. Pulp and paper mills, steel foundries, and organic chemical
      manufacturing facilities also discharge wastes of noteworthy potency. Treatment
      and remediation of some wastes, such as pulp and paper mill effluents, have been
      shown to reduce or eliminate genotoxicity. However, in other cases, treatment and
      remediation have been shown to enhance genotoxicity, such as for fungal treatment
      of oils. Analyses of samples collected from areas known to receive industrial
      wastes and effluents have shown that genotoxins can accumulate in the receiving
      environment and have adverse effects on indigenous biota. The evaluation of
      hazardous wastes and effluents by genotoxicity assays may provide data useful not
      only for hazard identification but for comparative risk assessment.

PMID- 9630653
TI  - Solution and solid state conformation of the human EGF receptor transmembrane
      region.
AB  - The epidermal growth factor receptor (EGFR) is a member of the tyrosine kinase
      family of signalling cell surface molecules. Signalling by this protein is
      mediated through binding of epidermal growth factor to its extracellular region
      ultimately leading to phosphorylation of several residues on the intracellular
      portion of the receptor. The only means of communication between the
      intracellular and extracellular domains is via the transmembrane region of the
      protein. In this work we describe the first structural studies of a 34-residue
      synthetic peptide (hEGFRp), representative of the human EGFR transmembrane
      region, using two-dimensional and 2H wideline NMR and CD spectroscopies. In water
      the peptide demonstrated a lack of regular secondary structure and existed as
      oligomers. Addition of the lipomimetic solvent, trifluoroethanol (TFE), led to
      the production of monomeric structured species. Analysis of NMR spectra of the
      hEGFRp indicated that an alpha-helix was present between residues M626 and R647.
      This observation was reinforced by solid state 2H NMR studies in lipid bilayers
      which showed typical 'Pake' spectra indicating axially symmetric motion. The
      helical region in hEGFRp commences four residues later than predicted via
      hydrophobicity profiles, and extends to include several charged arginine residues
      which would lie on the cytosolic side of the membrane. These observations provide
      the first evidence that the transmembrane alpha-helical region in EGFR may not
      only traverse the membrane but may continue to the cytosolic region near T654, an
      important phosphorylation site.

PMID- 9630654
TI  - Examination of DNA-binding activity of neuronal transcription factors by
      electrophoretical mobility shift assay.
AB  - Electrophoretical mobility shift assay (EMSA) is a simple, rapid, and highly
      sensitive technique for detection of single- or double-stranded DNA-binding
      proteins such as transcription factors in crude nuclear extracts (F.M. Ausubel,
      R. Brent, R.E. Kingston, D. D. Moore, J.G. Seidman, J.A. Smith, K. Struhl (Eds.),
      Current Protocols in Molecular Biology, Greene Publishing Associates and Wiley
      Interscience, 1989, pp. 12.0.1-12.2.10 [1]; J. Carey, Gel Retardation. Methods
      Enzymol., 208 (1991) 103-117 [2]). By using this technique, it is possible to
      quantify the abundance, relative affinity and binding specificity of DNA-binding
      proteins. Since proteins which bind specifically to radiolabeled DNA probes
      retard the mobility of the probe during electrophoresis (it also called gel
      retardation assay), discrete bands correspond to the individual DNA-protein
      complexes. Furthermore, EMSA allows one to determine which member(s) of a certain
      protein family are included in the DNA-protein complex by means of specific
      antibodies raised against the DNA-binding protein (supershift assay).

PMID- 9630655
TI  - Vasopressin-induced calcium signaling in cultured cortical neurons.
AB  - Earlier autoradiographic studies from our laboratory detected vasopressin
      recognition sites in the mammalian cerebral cortex [R.E. Brinton, K.W. Gee, J.K.
      Wamsley, T.P. Davis, H.I. Yamamura, Regional distribution of putative vasopressin
      receptors in rat brain and pituitary by quantitative autoradiography, Proc. Natl.
      Acad. Sci. U. S.A., 81 (1984) 7248-7252; C. Chen, R.D. Brinton, T.J. Shors, R.F.
      Thompson, Vasopressin induction of long-lasting potentiation of synaptic
      transmission in the dentate gyrus, Hippocampus, 3 (1993) 193-204]. More recently,
      we have detected mRNA for the V1a vasopressin receptors (V1aRs) in cultured
      cortical neurons [R.S. Yamazaki, Q. Chen, S.S. Schreiber, R.D. Brinton, V1a
      Vasopressin receptor mRNA expression in cultured neurons, astroglia, and
      oligodendroglia of rat cerebral cortex, Mol. Brain Res., 45 (1996) 138-140]. To
      determine whether these recognition sites are functional receptors, we have
      pursued the signal transduction mechanism associated with the V1a vasopressin
      receptor in enriched cultures of cortical neurons. Results of these studies
      demonstrate that exposure of cortical neurons to the selective V1 vasopressin
      receptor agonist, [Phe2,Orn8]-vasotocin, (V1 agonist) induced a significant
      accumulation of [3H]inositol-1-phosphate ([3H]IP1). V1 agonist-induced
      accumulation of [3H]IP1 was concentration dependent and exhibited a linear dose
      response curve. Time course analysis of V1 agonist-induced accumulation of
      [3H]IP1 revealed a significant increase by 20 min which then decreased gradually
      over the remaining 60 min observation period. V1 agonist-induced accumulation of
      [3H]IP1 was blocked by a selective V1a vasopressin receptor antagonist,
      (Phenylac1, D-Tyr(Me)2, Arg6,8, Lys-NH29)-vasopressin. Results of calcium
      fluorometry studies indicated that V1 agonist exposure induced a marked and
      sustained rise in intracellular calcium which was abolished in the absence of
      extracellular calcium. The loss of the rise in intracellular calcium was not due
      to a failure to induce PIP2 hydrolysis since activation of the
      phosphatidylinositol pathway occurred in the absence of extracellular calcium. V1
      agonist activation of calcium influx was then investigated. V1 agonist-induced
      45Ca2+ uptake was concentration dependent with a biphasic time course at 250 nM.
      Preincubation with the L-type calcium channel blocker, nifedipine, blocked V1
      agonist-induced calcium influx suggesting V1 agonist-induced L-type calcium
      channel activation in cortical neurons. Furthermore, V1 agonist-induced calcium
      influx was blocked by both bisindolyleimide I (PKC inhibitor) and U-73122 (PLC
      inhibitor) suggesting a modulation of V1 agonist-induced L-type calcium channel
      activation by downstream components of the phosphatidylinositol signaling pathway
      such as protein kinase C. These results indicate that in cultured cortical
      neurons, V1a vasopressin receptor activation leads to induction of the
      phosphatidylinositol signaling pathway, influx of extracellular calcium via L
      type calcium channel activation, and a rise in intracellular calcium which is
      dependent on V1a receptor activated influx of extracellular calcium. These data
      are the first to demonstrate an effector mechanism for the V1 vasopressin
      receptor in the cerebral cortex and provide a potential biochemical mechanism
      that may underlie vasopressin enhancement of memory function.

PMID- 9630656
TI  - Preferential expression of cholesteryl ester transfer protein mRNA by stromal
      vascular cells of human adipose tissue.
AB  - Cholesteryl ester transfer protein (CETP) mRNA is more abundantly expressed in
      small mature adipocytes as compared to large, lipid-rich adipocytes [Radeau et
      al., J. Lipid Res. 36 (1995) 2552-2561]. In the present study, the stromal
      vascular fraction (SVF) of human adipose tissue was isolated and the presence of
      very small fat cells in this fraction confirmed by electron microscopy and by
      demonstrating the presence of mRNA for adipsin and for CCAAT enhancer binding
      protein alpha (C/EBPalpha), a marker of adipocyte differentiation. sn-Glycerol 3
      phosphate dehydrogenase (GPDH) activity was present in the SVF but not in the
      preadipocyte fraction. Northern blot analysis of human adipose tissue
      demonstrated that CETP mRNA expression was significantly greater (+96%, P<0.03)
      in stromal-vascular cells (SVC) as compared to mature fat cells. By comparison,
      lipoprotein lipase mRNA expression was lower (-75%, P<0.03) in SVC while
      apolipoprotein E mRNA expression was not significantly different in SVC as
      compared to isolated adipocytes. By RT-PCR analysis, we demonstrated that CETP
      mRNA was expressed by human pre-adipocytes at levels less than those of SVC and
      adipocytes. The absence of monocytes/macrophages in SVC was confirmed by the
      absence of FcgammaRIII (CD16) mRNA in these fractions. These data demonstrate
      that CETP mRNA is most highly expressed in the immature fat cells of human
      adipose tissue, consistent with other experiments from this laboratory
      demonstrating that CETP plays an important local role in adipocyte cholesterol
      accumulation.

PMID- 9630657
TI  - Evolution of the cytochrome P450 superfamily: sequence alignments and
      pharmacogenetics.
AB  - The evolution of the cytochrome P450 (CYP) superfamily is described, with
      particular reference to major events in the development of biological forms
      during geological time. It is noted that the currently accepted timescale for the
      elaboration of the P450 phylogenetic tree exhibits close parallels with the
      evolution of terrestrial biota. Indeed, the present human P450 complement of
      xenobiotic-metabolizing enzymes may have originated from coevolutionary 'warfare'
      between plants and animals during the Devonian period about 400 million years
      ago. A number of key correspondences between the evolution of P450 system and the
      course of biological development over time, point to a mechanistic molecular
      biology of evolution which is consistent with a steady increase in atmospheric
      oxygenation beginning over 2000 million years ago, whereas dietary changes during
      more recent geological time may provide one possible explanation for certain
      species differences in metabolism. Alignment between P450 protein sequences
      within the same family or subfamily, together with across-family comparisons, aid
      the rationalization of drug metabolism specificities for different P450 isoforms,
      and can assist in an understanding of genetic polymorphisms in P450-mediated
      oxidations at the molecular level. Moreover, the variation in P450 regulatory
      mechanisms and inducibilities between different mammalian species are likely to
      have important implications for current procedures of chemical safety evaluation,
      which rely on pure genetic strains of laboratory bred rodents for the testing of
      compounds destined for human exposure.

PMID- 9630658
TI  - Neurite outgrowth of neuroblastoma cells overexpressing alpha and beta isoforms
      of Ca2+/calmodulin-dependent protein kinase II-effects of protein kinase
      inhibitors.
AB  - Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) is one of the most
      abundant protein kinases in the brain and has a broad substrate specificity [M.K.
      Bennett, N.E. Erondu, M.B. Kennedy, Purification and characterization of a
      calmodulin-dependent protein kinase that is highly concentrated in brain, J.
      Biol. Chem. 258 (1983) 12735-12744 [1]; J.R. Goldenring, B. Gonzalez, J.S.
      McGuire, Jr., R.J. DeLorenzo, Purification and characterization of a calmodulin
      dependent kinase from rat brain cytosol able to phosphorylate tubulin and
      microtubule-associated proteins, J. Biol. Chem. 258 (1983) 12632-12640 [4]; M.B.
      Kennedy, P. Greengard, Two calcium/calmodulin-dependent protein kinases, which
      are highly concentrated in brain, phosphorylate protein I at distinct sites,
      Proc. Natl. Acad. Sci. U.S.A. 78 (1981) 1293-1297 [10]; T. Yamauchi, H. Fujisawa,
      Evidence for three distinct forms of calmodulin-dependent protein kinases from
      rat brain, FEBS Lett. 116 (1980) 141-144 [20]; T. Yamauchi, H. Fujisawa,
      Purification and characterization of the brain calmodulin-dependent protein
      kinase (kinase II), which is involved in the activation of tryptophan 5
      monooxygenase, Eur. J. Biochem. 132 (1983) 15-21 [21]]. The alpha and beta
      isoforms of CaM kinase II are known to be expressed almost exclusively in the
      brain [P.I. Hanson, H. Schulman, Ca2+/calmodulin-dependent protein kinases, Annu.
      Rev. Biochem. 61 (1992) 559-601 [7]]. To elucidate the cellular function of CaM
      kinase II, we introduced cDNA of wild-type CaM kinase II alpha- or beta-isoform,
      and of mutant alpha-isoform (Ala-286 kinase) into two different types of
      neuroblastoma, Neuro2a (Nb2a) and NG108-15, thus generating cell lines stably
      producing elevated levels of these kinases. The mutant alpha-isoform is markedly
      suppressed in its autophosphorylation by replacement of Thr-286 with Ala [Y.-L.
      Fong, W.L. Taylor, A.R. Means, T.R. Soderling, Studies of the regulatory
      mechanism of Ca2+/calmodulin-dependent protein kinase II. Mutation of threonine
      286 to alanine and aspartate, J. Biol. Chem. 264 (1989) 16759-16763 [3]; P.I.
      Hanson, M.S. Kapiloff, L.L. Lou, M.G. Rosenfeld, H. Schulman, Expression of a
      multifunctional Ca2+/calmodulin-dependent protein kinase and mutational analysis
      of its autoregulation, Neuron 3 (1989) 59-70 [6]; S. Ohsako, H. Nakazawa, S.
      Sekihara, A. Ikai, T. Yamauchi, Role of Threonine-286 as autophosphorylation site
      for appearance of Ca2+-independent activity of calmodulin-dependent protein
      kinase II alpha subunit, J. Biochem. 109 (1991) 137-143 [15]]. We provided
      evidence that CaM kinase II played a role in regulating neurite outgrowth and
      growth cone motility in these cells, and that the autophosphorylation is
      essential for the kinase to sufficiently exert its cellular function in vivo [Y.
      Goshima, S. Ohsako, T. Yamauchi, Overexpression of Ca2+/calmodulin-dependent
      protein kinase II in Neuro2a and NG108-15 neuroblastoma cell lines promotes
      neurite outgrowth and growth cone motility, J. Neurosci. 13 (1993) 559-567 [5]].
      Neurite outgrowth was further stimulated by treatment with 1-(5
      isoquinolinesulfonyl)-2-methylpiperazine (H-7) or chelerythrine, inhibitors of
      protein kinase C [T. Nomura, K. Kumatoriya, Y. Yoshimura, T. Yamauchi,
      Overexpression of alpha and beta isoforms of Ca2+/calmodulin-dependent protein
      kinase II in neuroblastoma cells-H-7 promotes neurite outgrowth, Brain Res. 766
      (1997) 129-141 [14]]. The morphological change stimulated with protein kinase
      inhibitors was rapid and was greater in the beta than alpha cells. Some
      substrates of CaM kinase II related to neurite outgrowth were detected in cells
      overexpressing the kinase stimulated with H-7. These results suggest that CaM
      kinase II and protein kinase C play an important role in the control of cell
      change. (c) 1998 Elsevier Science B.V. All rights reserved.

PMID- 9630659
TI  - Mucin gene (MUC 2 and MUC 5AC) upregulation by Gram-positive and Gram-negative
      bacteria.
AB  - Bacterial infection of the lung is associated with mucin overproduction. In
      partial explanation of this phenomenon, we recently reported that supernatant
      from the Gram-negative organism Pseudomonas (P.) aeruginosa contained an activity
      that upregulated transcription of the MUC 2 mucin gene [J.-D. Li, A. Dohrman, M.
      Gallup, S. Miyata, J. Gum, Y. Kim, J. Nadel, A. Prince, C. Basbaum,
      Transcriptional activation of mucin by P. aeruginosa lipopolysaccharide in the
      pathogenesis of cystic fibrosis lung disease, Proc. Natl. Acad. Sci. U.S.A., 94
      (1997) 967-972]. The purpose of the present study was to determine whether mucin
      genes other than MUC 2 are so regulated and whether Gram-positive organisms also
      contain mucin stimulatory activity. Results from in situ hybridization and RNase
      protection assays showed that P. aeruginosa upregulates MUC 5AC as well as MUC 2
      in both bronchial explants and cultured airway epithelial cells. The upregulation
      of both genes by P. aeruginosa can be mimicked by lipopolysaccharide (LPS) and
      can be blocked by the tyrosine kinase inhibitor genistein. In addition, both
      genes are upregulated by a variety of Gram-positive as well as Gram-negative
      organisms showing the same rank order of potency. These data indicate the
      existence of a general mechanism by which epithelial cells respond to the
      presence of bacteria by increasing mucin synthesis.

PMID- 9630660
TI  - Analysis of binding and membrane destabilization of phospholipid membranes by
      surfactant apoprotein B.
AB  - To further elucidate the nature of the molecular interactions of surfactant
      apoprotein B (SP-B) with phospholipid (PL) membranes, we studied the binding of
      SP-B to PL membranes and the lipid-dependency of its subsequent effects on
      leakage and fusion of membranes. SP-B binding to membranes was studied by
      labeling the protein with the fluorophore 7-nitro-2,1,3-benzoxadiazol-4-yl (NBD)
      and measuring the fluorescence of the labeled protein in the presence of varying
      amounts of dipalmitoylphosphatidylcholine-egg phosphatidylglycerol (DPPC-eggPG; 7
      3). Leakage of contents from liposomes made of DPPC and varying molar fraction of
      egg phosphatidylcholine (eggPC) or eggPG was assessed by measuring the
      fluorescence of entrapped water-soluble probes ANTS and DPX. Fusion of membranes
      was assessed by measuring the fluorescence of membrane-bound NBD
      phosphatidylethanolamine (NBD-PE) and rhodamine-PE (RHO-PE). We found that SP-B
      bound to PL membranes with high affinity and appeared to irreversibly cluster at
      the membrane surface, leading to graded release of the vesicle contents and
      eventually fusion of the membranes with increasing protein-lipid ratios. All
      lipid mixtures tested were susceptible to the membrane disruptive effects of SP
      B, but DPPC-eggPG membranes displayed a biphasic response to increasing molar
      fractions of eggPG, whereas increasing fractions of eggPC elicited a monotonic
      response.

PMID- 9630661
TI  - Differential reactivities of hypochlorous and hypobromous acids with purified
      Escherichia coli phospholipid: formation of haloamines and halohydrins.
AB  - Hypochlorous (HOCl) and hypobromous (HOBr) acids are strong oxidants derived from
      myeloperoxidase and eosinophil peroxidase, the major antimicrobial enzymes of
      neutrophils and eosinophils, respectively. These oxidants are highly reactive
      with a wide range of biomolecules. At physiological pH, both HOCl and HOBr react
      readily with amines to form haloamines and with the unsaturated bonds of fatty
      acids to form halohydrins. We have investigated which of these reactions occur
      with phosphatidylethanolamine (PE), the predominant phospholipid of Escherichia
      coli. The formation of haloamines was determined by TLC and colorimetrically and
      the formation of halohydrins was determined by TLC and GC-MS. With HOCl,
      chloramines were much the preferred product and chlorohydrins were formed in
      substantial amounts only when HOCl was in excess of the amount required to
      convert the amine to the dichloramine. With HOBr at all concentrations,
      bromamines and bromohydrins were formed concurrently, indicating a greater
      relative reactivity with unsaturated fatty acids than with HOCl. The bromamine
      derivatives of PE, and other primary amines, were found to be more reactive than
      the equivalent chloramines, and were able to brominate the unsaturated bonds of
      fatty acids. Bromohydrins (formed directly or through the action of bromamines)
      may, therefore, be suitable biomarkers for the production of HOBr in vivo.

PMID- 9630662
TI  - Real-time measurement of ischemia-evoked glutamate release in the cerebral cortex
      of four and eleven vessel rat occlusion models.
AB  - Interstitial levels of the neurotransmitter glutamate and cerebral blood flow
      changes were compared in two models of rat forebrain ischemia using the dialysis
      electrode technique and laser doppler flowmetry with brain temperature
      controlled. Ten-minute periods of cerebral ischemia were elicited by the four and
      an eleven vessel occlusion and compared to carotid artery transection. Elapsed
      time from the onset of ischemia to the ischemic plateau was 76.8+/-57.9 s in 4VO
      vs. 14.8+/-1.3 s in 11VO animals. Percent residual cerebral blood flow (CBF) was
      13.5+/-8.8% during 4VO as opposed to 4.5+/-2.9% during 11VO. Concomitantly,
      cerebral glutamate levels rose to 255. 7+/-72.8 micromol l-1 in the 4VO animals
      in comparison with levels of 138.5+/-78.7 and 135.7+/-40.2 micromol l-1 in the
      11VO and carotid transection animals. During the first 89.6+/-47.4 s of
      reperfusion, glutamate levels rose to a second higher peak of 315. 1+/-179.2
      micromol l-1 in 7 of 12 animals. Following reperfusion, glutamate levels in the
      4VO and 11VO animals returned towards basal levels. This study demonstrates that
      11VO causes a rapid drop in CBF to near zero levels, better mimicking complete
      forebrain ischemia than the traditional 4VO technique. Moreover, the 'low flow'
      state of cerebral ischemia, produced by traditional 4VO, results in a higher
      interstitial level of glutamate than a 'no flow' state, as exhibited by the 11VO
      technique. The dialysis electrode, used simultaneously with laser doppler
      flowmetry, real-time data acquisition, and continuous brain temperature control,
      in this new rat model, provides real-time evidence that glutamate levels in the
      interstitial space are enhanced during a low flow state of cerebral ischemia.
      Furthermore, not before demonstrated, glutamate transients are seen to occur
      during the first 90 s of reperfusion, and, to the best of our knowledge, the
      glutamate levels recorded by this technique are the highest in the literature.

PMID- 9630663
TI  - A rapid and sensitive assay for measuring mitochondrial metabolic activity in
      isolated neural tissue.
AB  - In the present study, we used the oxidation-reduction sensitive dye Alamar Blue,
      a fluorometric/colorimetric indicator of metabolic activity, as a tool for
      examining mitochondrial function in rat spinal cord synaptosomes. At 15 min
      following incubation, Alamar Blue fluorescence levels were found to increase by 3
      fold, and could be detected in samples containing as little as 25 microg of
      protein. Alamar Blue is non-toxic, making it possible to obtain measures of the
      metabolic rate and the maximal functional capacity of mitochondria in a single
      sample. The findings of this study demonstrate that Alamar Blue fluorescence
      levels increased in a near linear fashion when samples were measured every 15 min
      for a period of 1 h. To document that the changes in Alamar Blue fluorescence are
      directly related to mitochondrial function, synaptosomes were pre-incubated with
      antimycin A (10 microM) or malonate (50 mM), both of which are potent inhibitors
      of mitochondrial function. Pretreatment with either compound significantly
      reduced the Alamar Blue fluorometric signal at all time points examined. These
      results provide evidence that Alamar Blue is a valuable analytical tool for
      examining mitochondrial function in synaptosomal preparations from neural tissue.
      Moreover, the properties of Alamar Blue are such that it provides a more
      sensitive and simpler indicator compared to indicators used in existing assays.

PMID- 9630664
TI  - Immunohistochemical characterization of transgenic mice highly expressing human
      lysosomal alpha-galactosidase.
AB  - Human lysosomal alpha-galactosidase predominantly hydrolyzes ceramide
      trihexoside. A transgenic mouse line, C57BL/6CrSIc-TgN(GLA) 1951 Rin, highly
      expressing human alpha-galactosidase, has been established and investigated
      biochemically and immunohistochemically in order to clarify the distribution of
      the expressed enzyme proteins and to evaluate it as a donor model of organ
      transplantation therapy for Fabry disease caused by a genetic defect of alpha
      galactosidase. In these transgenic mice, about five copies of the transgene were
      integrated, and alpha-galactosidase activity was expressed in liver, kidney,
      heart, spleen, small intestine, submaxillary gland, skeletal muscle, cerebrum,
      cerebellum, bone marrow cells and serum. The enzyme activity was about 22 to
      11,080-fold higher than that in non-transgenic mice. In liver, heart and kidney
      tissues, which are important organs for transplantation studies, sufficient
      amounts of alpha-galactosidase mRNAs were transcribed, and the expressed enzymes,
      with molecular weights of 54-60 kDa, are abundant in the liver (enzyme activity:
      53,965 nmol h-1 mg-1 protein) and heart (39,906 nmol h-1 mg-1 protein), followed
      by in the kidney tissue (9177 nmol h-1 mg-1 protein), respectively. An
      immunohistochemical microscopic study clearly demonstrated the distribution of
      the expressed enzyme proteins in kidney and liver tissues. Highly expressed alpha
      galactosidase was detected in glomerular cells, tubular cells and hepatocytes.
      These transgenic mice will be useful as a donor model for experimental organ
      transplantation, and also it will enable recurrent biopsies and long-term
      observation. The organ transplantation data on mice will provide us with
      important information.

PMID- 9630665
TI  - A two focal plane method for digital quantification of nuclear immunoreactivity
      in large brain areas using NIH-image software.
AB  - In principle, digital acquisition of cell-count data from serially-sectioned
      immunocytochemical material is a straightforward enterprise. First, a serial
      brain section is magnified by use of a microscope interfaced to a computer. Then,
      using appropriate hardware and software, a digital image is captured, and
      cellular profiles of interest are segmented from background objects according to
      mean grayscale intensity and pixel area. Ideally, the cells of interest would be
      uniformly distinguishable from other objects or areas of the image, with respect
      to grayscale intensity and size. However, due to non-uniformity in background
      staining of neuropil, immunocytochemical material often departs markedly from
      this ideal situation. As a consequence, determining grayscale intensity and cell
      size cutoff values which separate cells of interest from background becomes
      laborious and arbitrary. This problem can be diminished by increasing the
      magnification of the digitized image, which increases the figure-ground
      resolution of the image. However, high-magnification images make tissue
      navigation difficult and require that multiple images be captured. This paper
      describes a two focal plane procedure for obtaining cell counts from nuclear
      stained immunocytochemistry material. This procedure allows the capturing and
      cell counting of relatively low-magnification images with high digital figure
      ground resolution.

PMID- 9630666
TI  - Structural investigations of basic amphipathic model peptides in the presence of
      lipid vesicles studied by circular dichroism, fluorescence, monolayer and
      modeling.
AB  - A cationic amphiphilic peptide made of 10 leucine and 10 lysine residues, and
      four of its fluorescent derivatives in which leucines were substituted by Trp
      residues at different locations on the primary sequence have been synthesized.
      The interactions of these five peptides with neutral anionic or cationic vesicles
      were investigated using circular dichroism, steady state and time-resolved
      fluorescence with a combination of Trp quenching by brominated lipid probes,
      monolayers, modeling with minimization and simulated annealing procedures. We
      show that all the five peptides interact with neutral and anionic DMPC, DMPG,
      DOPC or egg yolk PC vesicles. The binding takes place whatever the peptide
      conformation in solution is. In the case of DMPC bilayers the binding free energy
      DeltaG is estimated at -8 kcal mole-1 and the number of phospholipid molecules
      involved is about 20-25 per peptide molecule. Peptides are bound as single
      stranded alpha helices orientated parallel to the bilayer surface. In the
      anchoring of phospholipid head groups around the peptides, the lipid molecules
      are not smeared out in a plane parallel to the membrane surface but are organized
      around the hydrophilic face of the alpha helices like 'wheat grains around an
      ear' and protrude outside the bilayer towards the solvent. We suggest that such a
      lipid arrangement generates transient structural defects responsible for the
      membrane permeability enhancement. When an electrical potential is applied, the
      axis of the peptide helices remains parallel to the membrane surface and does not
      reorient to give rise to a bundle of helix monomers that forms transmembrane
      channels via a 'barrel stave' mechanism. The penetration depth of alpha helices
      in relation to the position of phosphorus atoms in the unperturbed lipid leaflet
      is estimated at 3.2 A.

PMID- 9630667
TI  - Fluorometric assay of nitrite and nitrate in brain tissue after traumatic brain
      injury and cerebral ischemia.
AB  - Nitric oxide synthase (NOS) is distributed within the brain, and nitric oxide
      (NO) is felt to be involved in the pathophysiology of deterioration after head
      injury and cerebral ischemia. This study determined the levels of the stable end
      products of NOS (NOx=nitrite+nitrate) after traumatic brain injury (TBI) and
      transient cerebral ischemia. A fluorometric assay using nitrate reductase and the
      NADPH regenerating system was used to quantitate NOx in ultrafiltered (10-kDa
      cutoff) cortical and hippocampal extracts after reduction of nitrate. In TBI
      rats, both the plasma and tissue showed a sharp increase in NOx levels 5 min
      after injury. Plasma NOx returned to control levels by 2 h after injury.
      Ipsilateral-cortex NOx levels returned to control levels approximately 6 h after
      injury and remained constant from 6-24 h. Contralateral-cortex returned near to
      control levels after 1 h. Hippocampus also followed a similar trend. In gerbils,
      there was a significant elevation in tissue NOx levels immediately after 10 min
      transient cerebral ischemia, which gradually returned to control levels over 24 h
      reperfusion. This striking burst of NO synthesis immediately after injury is
      clearly evident whether the injury is head trauma or ischemia, or whether the
      measurements were performed on tissue or plasma. It is unknown whether
      endothelial NOS, neuronal NOS, or both caused the elevation of the NO end
      products seen after the CNS insults.

PMID- 9630668
TI  - Isoprenylation of polypeptides in the nematode Caenorhabditis elegans.
AB  - Covalent modification of eucaryotic proteins, involving addition of isoprenyl
      groups, is a widespread phenomenon. Here we provide direct evidence for this form
      of covalent modification in the free-living nematode, Caenorhabditis elegans.
      Following incubation in the presence of [3H]mevalonolactone, specific C. elegans
      polypeptides became labelled in both aqueous and detergent (Triton X-114)
      enriched extracts. Chemical and GC-MS analysis of modifying groups, cleaved from
      C. elegans polypeptides, revealed that geranylgeranylation and, to a lesser
      extent, farnesylation of target polypeptides occurred. Immunoblot analysis
      provided preliminary evidence that the ras-like let-60 polypeptide was a target
      for isoprenylation in C. elegans.

PMID- 9630669
TI  - Contribution of two missense mutations (G71R and Y486D) of the bilirubin UDP
      glycosyltransferase (UGT1A1) gene to phenotypes of Gilbert's syndrome and Crigler
      Najjar syndrome type II.
AB  - In our mutation analyses of bilirubin UDP glycosyltransferase (UGT1A1) gene, we
      encountered six patients with Crigler-Najjar syndrome type II who were double
      homozygotes for G71R and Y486D, a patient with Gilbert's syndrome who was a
      single homozygote for G71R and six patients with Gilbert's syndrome who were
      single heterozygote for G71R. To clarify the role of each mutation in the
      occurrence of the two syndromes, we made four mutant expression models. Relative
      UGT1A1 activity of a single homozygous model of G71R was 32.2+/-1.6% of normal,
      that of a single homozygous model of Y486D was 7.6+/-0.5%, that of a double
      homozygous model of G71R and Y486D was 6.2+/-1.6% and that of a heterozygous
      model of G71R was 60.2+/-3.5%. The decreased activities of the single homozygous
      model of G71R and the double homozygous model were at an appropriate level to be
      diagnosed as Gilbert's syndrome and CN-II, respectively. The activity of a single
      heterozygous model of G71R was somewhat high to develop to the phenotype of
      Gilbert's syndrome, suggesting the presence of additional factors for the
      etiology of Gilbert's syndrome.

PMID- 9630670
TI  - Adenosine potentiates the delayed-rectifier potassium conductance but has no
      effect on the hyperpolarization-activated Ih current in frog melanotrophs.
AB  - The effects of adenosine on the voltage-sensitive delayed-rectifier K+ (IK)
      currents and hyperpolarization-activated cationic inward current (Ih) were
      studied in cultured frog melanotrophs using the whole-cell configuration of the
      patch-clamp technique. The A1 receptor agonist R-N6-phenylisopropyl-adenosine (R
      PIA; 50 microM) reversibly increased IK. Perfusion of dibutyryl-cAMP (1 mM) in
      the external solution did not modify the R-PIA-induced enhancement of IK.
      Pretreatment of melanotrophs with pertussis toxin (1 microg/ml; 12 h) totally
      abolished the R-PIA-evoked response. Application of hyperpolarizing voltage
      pulses from -60 to -120 mV to melanotrophs induced a two-component inward current
      corresponding to an Ih-like conductance. This conductance was characterized by a
      high K+ selectivity and a low Na+ permeability and was resistant to tetrodotoxin
      (1 microM). R-PIA had no effect on Ih. The present study demonstrates that in
      frog melanotrophs adenosine inhibits the electrical activity by activating IK
      through an A1 receptor subtype coupled to a pertussis toxin-sensitive pathway
      independent of the cAMP/PKA system. This study also demonstrates the existence of
      a Ih conductance in frog melanotrophs which is not modulated by A1 receptors.

PMID- 9630671
TI  - Adduct formation, mutagenesis and nucleotide excision repair of DNA damage
      produced by reactive oxygen species and lipid peroxidation product.
AB  - Reactive oxygen species are formed constantly in living organisms, as products of
      the normal metabolism, or as a result of many different environmental influences.
      Here we review the knowledge of formation of DNA damage, the mutations caused by
      reactive oxygen species and the role of the excision repair processes, that
      protect the organism from oxidative DNA damage. In particular, we have focused on
      recent studies that demonstrate the important role of nucleotide excision repair.
      We propose two major roles of nucleotide excision repair as 1) a backup when base
      excision repair of small oxidative lesions becomes saturated, and as 2) a primary
      repair pathway for DNA damage produced by lipid peroxidation products.

PMID- 9630672
TI  - Measurement of tryptophan hydroxylase mRNA levels by competitive RT-PCR.
AB  - Tryptophan hydroxylase (TPH) is the rate limiting enzyme in serotonin
      biosynthesis [D.G. Grahame-Smith, Tryptophan hydroxylation in brain, Biochem.
      Biophys. Res. Commun. 16 (1964) 586-592 [19]]. As such, the TPH gene is a likely
      target for modulation of serotonergic function, which has been associated with
      several psychiatric disorders [E.C. Azmitia, P.M. Whitaker-Azmitia, Awakening the
      sleeping giant: anatomy and plasticity of the brain serotonergic system, J. Clin.
      Psychiatry 52 (12, Suppl.) (1991) 4-16 [1]; R.P. Hart, R. Yang, L.A. Riley., T.L.
      Green, Post-transcriptional control of tryptophan hydroxylase gene expression in
      rat brain stem and pineal gland, Mol. Cell. Neurosci. 2 (1991) 71-77 [20]; M.J.
      Owens, C.B. Numeroff, Role of serotonin in the pathophysiology of depression:
      focus on the serotonin transporter, Clin. Chem. 40 (1994) 288-295 [24]].
      Unfortunately, it has been technically difficult to measure TPH mRNA levels in
      central serotonergic neurons due to its low levels. For example, detection with
      ribonuclease protection assays requires pooling of 5-10 dissected brainstems
      [M.C. Darmon, B. Guibert, V. Leviel, M. Ehret, M. Maitre, J. Mallet, Sequence of
      two mRNAs encoding active rat tryptophan hydroxylase, J. Neurochem. 51 (1988) 312
      316 [15]; B.L. Jacobs, E.C. Azmitia, Structure and function of the brain
      serotonin system, Physiol. Rev. 72 (1992) 165-229 [21]]. This protocol describes
      the use of competitive RT-PCR to measure TPH mRNA levels from rat brain. First
      described in 1988, competitive RT-PCR has become an accepted method of measuring
      RNA abundance [M. Clementi, S. Menzo, P. Bagnarelli, A. Manzin, A. Valenza, P.E.
      Varaldo, Quantitative PCR and RT-PCR in virology, PCR Methods Appl. 2 (1994) 191
      196 [12]; N.C.P. Cross, Quantitative PCR techniques and applications, Br. J.
      Haematol. 89 (1995) 693-697 [14]; K.P. Foley, M.W. Leonard, J.D. Engel,
      Quantitation of RNA using the polymerase chain reaction, Trends Genet. 9 (1993)
      380-385 [17]; P.D. Siebert, J.W. Larrick, Competitive PCR, Nature 359 (1992) 558
      [27]]. Competitive RT-PCR uses co-amplification with a known quantity of an in
      vitro transcribed RNA which amplifies using the same primers and thus competes
      for reactants with the product of interest. As the two products amplify with the
      same efficiency, the relative abundance of the two amplification products remains
      constant, and thus can be used to determine initial tissue TPH mRNA levels [G.
      Gilliland, S. Perrin, K. Blanchard, H.F. Bunn, Analysis of cytokine mRNA and DNA:
      detection and quantitation by competitive polymerase chain reaction, Proc. Natl.
      Acad. Sci. U.S.A. 87 (1990) 2725-2729 [18]; A.M. Wang, M. V. Doyle, D.F. Mark,
      Quantitation of mRNA by the polymerase chain reaction, Proc. Natl. Acad. Sci.
      U.S.A. 86 (1989) 9717-9721 [31]]. We first demonstrate equivalent results between
      RNA slot blots and competitive RT-PCR using the CA77 thyroid C cell line [M.S.
      Clark, A. F. Russo, Tissue-specific glucocorticoid regulation of tryptophan
      hydroxylase mRNA levels, Mol. Brain Res. 48 (1997) 346-354 [9]]. We then describe
      the use of competitive RT-PCR to measure TPH mRNA levels in RNA isolated from rat
      brain poly-A+ RNA.

PMID- 9630673
TI  - Proton NMR spectroscopic analysis of multiple acyl-CoA dehydrogenase deficiency-
      capacity of the choline oxidation pathway for methylation in vivo.
AB  - Proton NMR spectra of urine from subjects with multiple acyl-CoA dehydrogenase
      deficiency, caused by defects in either the electron transport flavoprotein or
      electron transport flavoprotein ubiquinone oxidoreductase, provide a
      characteristic and possibly diagnostic metabolite profile. The detection of
      dimethylglycine and sarcosine, intermediates in the oxidative degradation of
      choline, should discriminate between multiple acyl-CoA dehydrogenase deficiency
      and related disorders involving fatty acid oxidation. The excretion rates of
      betaine, dimethylglycine (and sarcosine) in these subjects give an estimate of
      the minimum rates of both choline oxidation and methyl group release from betaine
      and reveal that the latter is comparable with the calculated total body methyl
      requirement in the human infant even when choline intake is very low. Our results
      provide a new insight into the rates of in vivo methylation in early human
      development.

PMID- 9630675
TI  - Effects of intracerebroventricularly infused histamine and selective H1, H2 and
      H3 agonists on food and water intake and urine flow in Wistar rats.
AB  - The actions of intracerebroventricularly-infused histamine and selective
      histamine H1, H2 and H3 receptor agonists on food and water intake and urine flow
      were studied in rats. It was found that 100-800 nmoles of histamine significantly
      suppressed feeding. The H1 agonist 2-(3- trifluoromethylphenyl)histamine (FMPH)
      decreased food intake, whereas the H2 agonist dimaprit was without effect.
      Histamine- and FMPH-induced suppressions of feeding were attenuated by blockade
      of H1 but not by H2 receptors. The results clearly demonstrate that activation of
      brain H1 receptors decreases food intake. In subsequent studies, we found that
      both metoprine and thioperamide, which increase histaminergic activity through
      different mechanisms, also reduced food intake. This finding indicates that the
      brain histaminergic system is associated with feeding behavior. The same is true
      with body water homeostasis. Histamine caused a long-lasting diuresis. Also
      dimaprit and metoprine increased urine flow and the blockade of H2 receptors
      abolished the diuretic responses to histamine and dimaprit. On the other hand,
      the H3 agonist (R)-alpha-methylhistamine elicited drinking and this effect could
      be prevented by thioperamide pretreatment. The results imply that activation of
      H3 receptors predominantly provokes drinking, whereas central H2 receptors
      mediate the diuretic effect of histamine.

PMID- 9630674
TI  - Hepatic lipase affects both HDL and ApoB-containing lipoprotein levels in the
      mouse.
AB  - Transgenic mice were created overproducing a range of human HL (hHL) activities
      (4-23-fold increase) to further examine the role of hepatic lipase (HL) in
      lipoprotein metabolism. A 5-fold increase in heparin releasable HL activity was
      accompanied by moderate (approx. 20%) decreases in plasma total and high density
      lipoprotein (HDL) cholesterol and phospholipid (PL) but no significant change in
      triglyceride (TG). A 23-fold increase in HL activity caused a more significant
      decrease in plasma total and HDL cholesterol, PL and TG (77%, 64%, 60%, and 24%
      respectively), and a substantial decrease in lipoprotein lipids amongst IDL, LDL
      and HDL fractions. High levels of HL activity diminished the plasma concentration
      of apoA-I, A-II and apoE (76%, 48% and 75%, respectively). In contrast, the
      levels of apoA-IV-containing lipoproteins appear relatively resistant to
      increased titers of hHL activity. Increased hHL activity was associated with a
      progressive decrease in the levels and an increase in the density of LpAI and
      LpB48 particles. The increased rate of disappearance of 125I-labeled human HDL
      from the plasma of hHL transgenic mice suggests increased clearance of HDL
      apoproteins in the transgenic mice. The effect of increased HL activity on
      apoB100-containing lipoproteins was more complex. HL-deficient mice have
      substantially decreased apoB100-containing low density lipoproteins (LDL)
      compared to controls. Increased HL activity is associated with a transformation
      of the lipoprotein density profile from predominantly buoyant (VLDL/IDL)
      lipoproteins to more dense (LDL) fractions. Increased HL activity from moderate
      (4-fold) to higher (5-fold) levels decreased the levels of apoB100-containing
      particles. Thus, at normal to moderately high levels in the mouse, HL promotes
      the metabolism of both HDL and apoB-containing lipoproteins and thereby acts as a
      key determinant of plasma levels of both HDL and LDL.

PMID- 9630676
TI  - Receptor mediated binding of two glycosylation forms of N-acetylgalactosamine-4
      sulphatase.
AB  - The lysosomal storage disorders are a group of inherited metabolic diseases each
      characterised by a relative or absolute deficiency of one or more of the
      lysosomal proteins involved in the hydrolysis of glycoconjugates or in the
      transport of the resulting product. Enzyme replacement therapies are under
      consideration for a number of these disorders and are based on the in vitro
      observation that cells from affected patients can be corrected by addition of
      exogenous enzyme. In this study, two glycosylation variants of the lysosomal
      enzyme N-acetylgalactosamine-4-sulphatase (4S) (the deficiency of which causes
      Mucopolysaccharidosis (MPS) type VI, (Maroteaux-Lamy syndrome) were made by
      expression of 4S cDNA in both wild type chinese hamster ovary (CHO-K1), and Lec1
      (N-acetylglucosaminyltransferase I deficient CHO-K1) cells. Differences in the
      glycosylation pattern of the two enzyme forms were demonstrated with
      endoglycosidase H and N-glycosidase F digestions. The receptor mediated binding
      of these two forms of 4S to two cell types, human skin fibroblasts and rat
      alveolar macrophages, was then analysed. We have shown that both enzyme forms
      bind to the mannose-6-phosphate receptor on human skin fibroblasts with equal
      affinity demonstrating that the degree of phosphorylation of mannose residues in
      the two forms is similar. However, using rat alveolar macrophages, we found that
      the binding/uptake of the two enzymes differs considerably. These results show
      that differences in glycosylation of lysosomal enzymes can be an important factor
      in altering enzyme uptake by different cell types. Thus, producing carbohydrate
      modification variants in this way may be useful for altering the distribution of
      exogenous enzyme in vivo.

PMID- 9630677
TI  - The effect of oxidative stress on structural transitions of human erythrocyte
      ghost membranes.
AB  - Differential scanning microcalorimetry was used to study the effect of oxidative
      stress induced by cumene hydroperoxide (CHP) and Fe2+ on structural transitions
      of membranes of human erythrocyte ghosts. The CHP homolysis was shown to cause:
      (a) reduction of the intensity of all structural transitions with the
      disappearance of B1- and D-transitions; (b) decrease in the enthalpy of oxidized
      membrane denaturation; (c) negative slope of thermograms; (d) anomalous growth of
      heat absorption by membranes above 72 degreesC. All these changes occurred until
      the ratio Fe2+/CHP/membranes<0.02:0.05:1 was reached, i.e., prior to the moment
      of maximal level of TBA-RS in membrane ghosts. We interpret changes in the
      character of heat absorption by oxidized membranes as perturbations in the
      structural organization and interactions inside the spectrin-actin-protein 4.1
      domains, the spectrin-protein 4.2 domain, as well as inside the domain of
      spectrin-ankyrin-cdB3 and the domain formed by the msdB3. These perturbations are
      associated mainly with the decrease in the concentration of native protein in the
      domains because of oxidative aggregation of proteins, as evidenced by SDS
      electrophoresis of oxidized membranes. Preincubation of membranes with tocopherol
      did not block the aggregation of proteins in electrophoresis and the decrease in
      the intensity of structural transitions, whereas it blocked completely the
      formation of TBA-RS, changes in the thermogram slope and the sharp rise in the
      heat absorption above 72 degreesC. This proves that these processes are
      determined by the thermotropic properties of the oxidized lipid bilayer of
      membranes and also provides evidence that the degradation of PUFA of
      phospholipids modifies both the structure of protein domains and the physical
      properties of the lipid bilayer of membranes.

PMID- 9630678
TI  - A method for triple fluorescence labeling with Vicia villosa agglutinin, an anti
      parvalbumin antibody and an anti-G-protein-coupled receptor antibody.
AB  - The aim of the original study [S.B. Bausch, C. Chavkin, Vicia villosa agglutinin
      labels a subset of neurons coexpressing both the mu opioid receptor and
      parvalbumin in the developing rat subiculum, Dev. Brain Res., 97, 1996, 169-177]
      [3] was to develop a method for identifying a subset of mu opioid receptor
      expressing interneurons in the rat subiculum for electrophysiological studies.
      Previous studies had shown that a subset of parvalbumin-positive neurons in the
      rat subiculum could be labeled with the lectin, Vicia villosa agglutinin (VVA)
      [C.T. Drake, K.A. Mulligan, T.L. Wimpey, A. Hendrickson, C. Chavkin,
      Characterization of Vicia villosa agglutinin-labeled GABAergic neurons in the
      hippocampal formation and in acutely dissociated hippocampus, Brain Res., 554,
      1991, 176-185] [11], and that mu opioid receptor immunoreactivity (-IR) and
      parvalbumin-IR were colocalized in a subset of neurons in the hippocampus and
      dentate gyrus [S.B. Bausch, C. Chavkin, Colocalization of mu and delta opioid
      receptors with GABA, parvalbumin and a G-protein-coupled inwardly rectifying
      potassium channel in the rodent brain, Analgesia, 1, 1995, 282-285] [2]. We
      hypothesized that a subset of mu opioid receptor-expressing neurons in the
      subiculum also would express the calcium binding protein, parvalbumin, and could
      be labeled with VVA. Labeling of live neurons with VVA [11] then could be used to
      identify these neurons. This protocol was designed to triple-label neurons
      expressing the mu opioid receptor, parvalbumin and the carbohydrate group, N
      acetylgalactosamine (which binds VVA [S.E. Tollefsen, R. Kornfeld, The B4 lectin
      from Vicia villosa seeds interacts with N-acetylgalactosamine residues alpha
      linked to serine or threonine residues in cell surface glycoproteins, J. Biol.
      Chem., 258, 1983, 5172-5176][M.P. Woodward, W.W. Young, R.A. Bloodgood, Detection
      of monoclonal antibodies specific for carbohydrate epitopes using periodate
      oxidation, J. Immunol. Methods, 78, 1985, 143-153] [25, 29]). VVA labeling and
      immunocytochemistry with an affinity-purified anti-mu opioid receptor antibody
      [S.B. Bausch, T.A. Patterson, M.U. Ehrengruber, H.A. Lester, N. Davidson, C.
      Chavkin, Colocalization of mu opioid receptors with GIRK1 potassium channels in
      rat brain: an immunocytochemical study, Recept. Channels, 3, 1995, 221-241] [4]
      and an anti-parvalbumin antibody [M.R. Celio, W. Baier, L. Scharer, P.A. de
      Viragh, C. Gerday, Monoclonal antibodies directed against the calcium binding
      protein parvalbumin, Cell Calcium, 9, 1988, 81-86] [8] were used to accomplish
      this goal. Immunofluorescence was used as the detection method; visualization was
      accomplished with three fluorophores with different excitation/emission spectra
      and a one laser confocal microscope. This protocol can be modified easily to
      triple-label neurons for other carbohydrate groups and proteins.

PMID- 9630679
TI  - Collateral hemodynamics after middle cerebral artery occlusion in Wistar and
      Fischer-344 rats.
AB  - We investigated whether the difference in infarction volume after occlusion of a
      long proximal segment of the middle cerebral artery between Wistar and Fischer
      344 rats, is caused by differences in collateral blood flow rate through
      leptomeningeal anastomoses. In view of the retrograde direction of collateral
      blood flow into the middle cerebral artery territory, we developed parasagittal
      laser-Doppler flowmetry. Using this method two laser-Doppler probes are placed on
      the cerebral cortex: probe 1 is placed near the anastomoses between the middle-
      and anterior cerebral artery, probe 2 is placed 2 mm further away from these
      anastomoses than probe 1. We found in both rat strains a comparable relation
      between the areas under the curve of the signal measured by both laser-Doppler
      probes for 2 h after middle cerebral artery occlusion. This relation is
      considered to be a measurement of the collateral blood flow rate into the middle
      cerebral artery territory through leptomeningeal anastomoses after middle
      cerebral artery occlusion. We conclude that collateral blood flow for the two
      strains were essentially similar for the initial 2 h after MCA occlusion.
      Although these collateral blood flows could have been different at a later time,
      it is unlikely that the interstrain difference in cerebral infarction volume
      between Wistar and Fischer-344 rats after proximal middle cerebral artery
      occlusion is caused by an apparent interstrain difference in the magnitude of
      collateral blood flow rate through leptomeningeal anastomoses. The parasagittal
      laser-Doppler flowmetry technique we developed for these experiments is currently
      successfully used in our laboratory to evaluate the efficacy of hemodynamically
      active pharmacotherapeutical agents in raising the collateral blood flow rate
      into the middle cerebral artery territory after middle cerebral artery occlusion.

PMID- 9630680
TI  - Antioxidant properties of butein isolated from Dalbergia odorifera.
AB  - The antioxidant properties of butein, isolated from Dalbergia odorifera T. Chen,
      were investigated in this study. Butein inhibited iron-induced lipid peroxidation
      in rat brain homogenate in a concentration-dependent manner with an IC50, 3.3+/
      0.4 microM. It was as potent as alpha-tocopherol in reducing the stable free
      radical diphenyl-2-picrylhydrazyl (DPPH) with an IC0.200, 9.2+/-1.8 microM. It
      also inhibited the activity of xanthine oxidase with an IC50, 5.9+/-0.3 microM.
      Besides, butein scavenged the peroxyl radical derived from 2,2-azobis(2
      amidinopropane) dihydrochloride (AAPH) in aqueous phase, but not that from 2,2
      azobis(2, 4-dimethylvaleronitrile) (AMVN) in hexane. Furthermore, butein
      inhibited copper-catalyzed oxidation of human low-density lipoprotein (LDL), as
      measured by conjugated dienes and thiobarbituric acid-reactive substance (TBARS)
      formations, and electrophoretic mobility in a concentration-dependent manner.
      Spectral analysis revealed that butein was a chelator of ferrous and copper ions.
      It is proposed that butein serves as a powerful antioxidant against lipid and LDL
      peroxidation by its versatile free radical scavenging actions and metal ion
      chelation.

PMID- 9630681
TI  - Irreversible dimerization/tetramerization and post-translational modifications
      inhibit proteolytic degradation of A beta peptides of Alzheimer's disease.
AB  - Experimental evidence increasingly implicates the beta-amyloid peptide in the
      pathogenesis of Alzheimer's disease. Beta-amyloid filaments dramatically
      accumulate in the neuritic plaques and vascular deposits as the result of the
      brain's inability to clear these structures. In this paper, we demonstrate that
      in addition to the intrinsic stability of A beta N-42, the time dependent
      generation of irreversibly associated A beta dimers and tetramers incorporated
      into A beta filaments are themselves resistant to proteolytic degradation. The
      presence of post-translational modifications such as isomerization of aspartyls 1
      and 7, cyclization of glutamyl 3 to pyroglutamyl and oxidation of methionyl 35,
      further contribute to the insolubility and stability of A beta. All these factors
      promote the accumulation of neurotoxic amyloid in the brains of patients with
      Alzheimer's disease, and should be considered in therapeutic strategies directed
      towards the dissociation of the brain's A beta filaments.

PMID- 9630682
TI  - Chromosome aberration assays in Crepis for the study of environmental mutagens.
AB  - Crepis capillaris (2n=6) is an excellent plant for the assay of chromosome
      aberrations after chemical treatment. C. tectorum (2n=8) has been used also in
      mutagenic studies, but to a much lesser extent. A protocol has been given for
      using root tips to study the cytological endpoints, such as chromosome breaks and
      exchanges, which follow the testing of chemicals in somatic cells. Meiotic
      endpoints have not been used in C. capillaris for testing potential chemical
      mutagens but should be considered, especially a meiotic micronucleus assay. From
      a literature survey, 81 chemicals are tabulated that have been assayed in 162
      Crepis assays for their clastogenic effects. Of the 162 assays that have been
      carried out, 40 are reported at giving a positive reaction (i.e., causing
      chromosome aberrations), 97 positive and with a dose response, 7 borderline
      positive, and 17 negative. Eighty-five percent of the chemicals gave a definite
      positive response. Assays for one chemical gave contrary results, and were not
      included in the above tabulation. The Crepis bioassay has been shown to be an
      excellent plant bioassay for assessing chromosome damage induced by chemicals and
      environmental pollutants.

PMID- 9630683
TI  - The role of the GLUT 4 transporter in regulating rat myoblast glucose transport
      processes.
AB  - Previous studies revealed an inverse relationship between GLUT 1 and GLUT 4
      expression in rat myoblasts [L. Xia, Z. Lu, T.C.Y. Lo, J. Biol. Chem., 268 (1993)
      23258-23266]. It was not clear whether these were coincidental or causal
      occurrences. To examine the regulatory roles of the GLUT 4 isoform, rat L6
      myoblasts were transfected with full length GLUT 4 cDNAs (2.5 kb) in the sense or
      antisense orientation. L6 myoblasts transfected with the GLUT 4 sense cDNA
      (L6/G4S transfectants) possessed much elevated levels of both endogenous GLUT 4
      transcripts (1.4 kb and 2.8 kb). Transport and immunofluorescence studies showed
      that this GLUT 4 sense cDNA was responsible for a functional GLUT 4 transporter.
      L6 cells transfected with the GLUT 4 antisense cDNA (L6/G4A transfectants)
      possessed only 6% of the L6 level in day 6 cultures. These antisense
      transfectants were essentially devoid of any functional GLUT 4 transporter. The
      activation of transcription of the endogenous GLUT 4 gene in L6/G4S myoblasts
      suggested auto-regulation of GLUT 4 expression. GLUT 3 expression and activity
      were not altered in both sense and antisense GLUT 4 transfectants. More
      interestingly, GLUT 1 expression was reduced in L6/G4S myoblasts, whereas it was
      elevated in L6/G4A myoblasts. This was the first direct evidence indicating GLUT
      4 might play an important role in suppressing GLUT 1 expression.

PMID- 9630684
TI  - Methylamine dehydrogenase is a light-dependent oxidase.
AB  - Quinoproteins may function either as oxidases or dehydrogenases, depending on the
      nature of their quinone prosthetic group. The tryptophan tryptophylquinone (TTQ)
      linked methylamine dehydrogenase (MADH) is relatively inert towards O2 in its
      reduced form. It is shown that on exposure to long range UV (ultaviolet) light,
      MADH is oxidized in the presence of O2 and exhibits substrate-dependent steady
      state oxidase activity. The effects of light are completely reversible, and
      oxidase activity is lost when the light is turned off. The light-dependent
      oxidation of MADH proceeds via a semiquinone intermediate which accumulates to
      near stoichiometric levels. The absorption of the light appears to provide energy
      to overcome a thermodynamic barrier to the transfer of an electron from TTQ to
      O2. These studies provide a basis for understanding what factors dictate whether
      an oxidoreductase is a dehydrogenase or an oxidase.

PMID- 9630685
TI  - Three-dimensional and ultrastructural ICAM-1 distribution in the choroid plexus,
      arachnoid membrane and dural sinus of inflammatory rats induced by LPS injection
      in the lateral ventricles.
AB  - To investigate immunological environment in the cerebrospinal fluid (CSF) system,
      ultrastructural and three-dimensional localization of intercellular adhesion
      molecule-1 (ICAM-1) was studied in the choroid plexus, arachnoid membrane and
      dural sinus of LPS-stimulated rats with immuno-SEM and TEM. The choroid plexus
      epithelial cells expressed rich ICAM-1 along the microvilli. The arachnoid
      trabeculae fibroblast-like cells demonstrated ICAM-1 expression on both sides
      facing the subarachnoid space moderately. The dural sinus endothelial cells,
      however, showed only few ICAM-1 expression and no specific localization. These
      results suggest that the choroid plexus and arachnoid membrane may play an
      important mutual role for leukocyte migration in the CSF system, and that the CSF
      system may function in immunoreaction independently of the vascular system with
      the aid of up-regulated ICAM-1 expression.

PMID- 9630686
TI  - Analysis of a naturally occurring mutation in sucrase-isomaltase: glutamine 1098
      is not essential for transport to the surface of COS-1 cells.
AB  - A glutamine for proline substitution at position 1098 was previously shown to
      result in accumulation of brush-border sucrase-isomaltase in the Golgi apparatus.
      The substitution is present in a highly homologous region of the protein, and
      results in a comparable accumulation when introduced into the same region in
      lysosomal alpha-glucosidase. To study the importance of the glutamine-1098, we
      analyzed the transport compatibility of two mutants in which glutamine-1098 is
      substituted by lysine or alanine. Both mutants were transported to the cell
      surface and processed comparable to wild type. We concluded that glutamine-1098
      is not essential for transport to the cell surface.

PMID- 9630687
TI  - An immunocytochemical technique with monoclonal antibodies to glycosphingolipids
      in rat primary cerebellar cultures: influence of detergent permeabilization.
AB  - Glycosphingolipids (GSLs) are highly expressed in the vertebrate central nervous
      system. GSLs have been implicated in a variety of phenomena involving cell-cell
      recognition, neurite outgrowth, synaptogenesis, transmembrane signalling and cell
      growth and differentiation. We recently determined the distribution of GSLs in
      rat brain tissues and in primary rat cerebellar cultures as well as using a
      number of MAbs to GSLs, which were generated and characterized in our laboratory.
      These results suggested that (i) the expression of GSLs was highly localized to a
      specific cell type and layer in the rat brain tissues and (ii) some GSLs may be
      useful markers for identifying cells in the primary cultures. In the present
      paper, we describe in detail an immunofluorescence technique for the detection of
      GSL expression in the primary cultures. We demonstrate that the localization of
      GSLs can be greatly influenced by detergent treatments.

PMID- 9630688
TI  - Dietary fish oil appears to prevent the activation of phospholipase C-gamma in
      lymphocytes.
AB  - Rats were fed on a low fat diet or on high fat diets which included coconut oil,
      olive oil, safflower oil, evening primrose oil or fish oil as the principal fat
      source. The level of phosphatidylinositol-4, 5-bisphosphate in spleen lymphocytes
      was unaffected by diet. However, the fish oil diet significantly decreased the
      concentration of inositol-1,4,5-trisphosphate in stimulated lymphocytes; this
      concentration was also reduced following olive oil feeding. Diet did not
      significantly affect the level of phospholipase C-gamma1 in spleen lymphocytes
      but the tyrosine phosphorylation state of this enzyme in stimulated lymphocytes,
      as well as that of a range of other proteins, was decreased following feeding the
      fish oil and, to a lesser extent, the olive oil diets. It is concluded that fish
      oil feeding appears to result in inhibition of one or more tyrosine kinases.

PMID- 9630689
TI  - A pyrophosphate synthase gene: molecular cloning and sequencing of the cDNA
      encoding the inorganic pyrophosphate synthase from Rhodospirillum rubrum.
AB  - The integrally membrane-bound, proton-pumping inorganic pyrophosphate (PPi)
      synthase in phototrophic bacteria is hitherto the only described alternative to
      the ATP synthase in biological electron transport phosphorylation. We have
      identified and sequenced the first gene coding for a pyrophosphate synthase. The
      deduced protein contains 660 amino acid residues and 15 putative membrane
      spanning segments. It is homologous to the vacuolar pyrophosphatases from plants.

PMID- 9630690
TI  - Age-related changes in thyroid hormone responsive protein (THRP) expression in
      cerebral tissue of rats.
AB  - To determine if aging in rats is associated with insensitivity of cerebral tissue
      to thyroid hormones (TH), the expression of a TH responsive protein or (THRP) in
      cerebral tissue was studied in male Fischer rats at 4, 12 and 24 months of age
      during euthyroid, hypothyroid and hyperthyroid states. The basal levels of THRP
      mRNA was significantly increased in 24-month-old and in 12-month-old rats while
      THRP mass measured by Western blots was decreased compared to 4-month-old rats.
      Compared to euthyroid rats, hyperthyroidism in 4-month-old rats was associated
      with 5.1-fold increase in THRP mRNA and 3.7-fold increase in protein content
      while in hyperthyroid aged rats, the increase of THRP mRNA was only 1.6-fold and
      the increase in the protein was 2.4-fold. Hypothyroidism did not significantly
      alter THRP or its mRNA in either young or aged rats. It is concluded that aging
      in rats is associated with reduced cerebral tissue responsiveness to thyroid
      hormones.

PMID- 9630691
TI  - Effects of electrical stimulation in the amygdala on ponto-geniculo-occipital
      waves in rats.
AB  - We examined the role of the amygdala in the modulation of sleep and ponto
      geniculo-occipital (PGO) waves in the rat. The amygdala projects massively, via
      its central nucleus, into brainstem regions involved in alerting and in the
      generation of rapid-eye movement (REM) sleep and PGO waves. Electrical
      stimulation of the central nucleus of the amygdala during REM sleep increased PGO
      wave amplitude. Stimulation during non-REM sleep decreased PGO wave frequency.
      The results indicate that the amygdala has a role in modulating brainstem neural
      mechanisms underlying alerting during sleep.

PMID- 9630692
TI  - A neuromagnetic normative data set for hemispheric sensory hand cortical
      representations and their interhemispheric differences.
AB  - Somatotopy of human hand primary sensory cortex has been studied
      neuromagnetically [C. Baumgartner, A. Doppelbauer, L. Deecke, D.S. Barth, J.
      Zeitlhofer, G. Lindinger, W.W. Sutherling, Neuromagnetic investigation of
      somatotopy of human hand somatosensory cortex, Exp. Brain Res. 87 (1991) 641
      648.] [1]. Investigation of sensory cortex devoted to the hand will be of major
      importance in relation to clinical recovery after sensorimotor deficits as well
      as an index of plasticity phenomena following alterations of peripheral nerves
      inputs. Here a normative data set has been constructed, on the basis of the
      neuromagnetic investigation of the primary sensory hand cortical representation
      in the two hemispheres of 20 healthy volunteers. This can be used to evaluate
      interhemispheric differences of the 'sensory' hand areas during experimental
      paradigms in the healthy as well as following patients with monohemispheric
      lesions. The localizations in each hemisphere of the cortical Equivalent Current
      Dipoles (ECDs) activated with the shortest latencies (N20m and P30m components)
      by separate stimulation of left and right median nerve, thumb and little finger
      were analysed. By considering the ECDs to thumb and little finger stimulation the
      boundaries of the hand cortical representation in primary sensory cortex, the
      'hand extension' was measured as the distance between the two. For all the
      considered parameters (related to N20m and P30m ECDs: latency, strength, spatial
      position in the individual head, 'hand extension', interhemispheric differences)
      the appropriate variable distribution was considered and by including the 98% of
      the healthy population normative limits were calculated.

PMID- 9630693
TI  - Citrate and isocitrate in plant metabolism.
AB  - The relevance of citrate and isocitrate metabolism in plants is discussed in
      connection with the different pathways for their conversions. The routes for
      citrate and isocitrate conversions are incorporated into the system of cross
      linked metabolic processes and may provide carbon skeletons for nitrogen
      assimilation and reducing equivalents for biosynthetic reactions, support the
      functioning of the glyoxylate cycle and play an important role in the TCA and
      energy metabolism as a whole. The possibility of the coupling of citrate and
      isocitrate metabolism with various electron transport systems is discussed from
      the point of view of the efficiency of the balancing cellular NAD(P)H/NAD(P)+ and
      ATP/ADP ratios. The role of citrate and isocitrate and their derivations as
      potent effectors of some enzymes is considered. Special attention is paid to the
      enzymes associated with citrate and isocitrate metabolism and to the mechanisms
      which regulate their activity. The possibilities of the coordination of the main
      processes of energy and biosynthetic metabolism at the level of citrate and
      isocitrate distribution are discussed.

PMID- 9630694
TI  - Strong synergistic anti-peroxidative effects of HDL3 and ascorbic acid against
      copper-catalyzed LDL peroxidation.
AB  - The aim of this study was to investigate the effects of high density lipoprotein
      3 (HDL3) and ascorbic acid (AsA) in combination on copper-catalyzed low density
      lipoprotein (LDL) peroxidation. LDL and HDL3 were isolated from sera of healthy
      volunteers. LDL protein, 200 microg/ml, was incubated in phosphate-buffered
      saline (PBS) containing 2.5 microM CuSO4 in the absence or presence of AsA, with
      HDL3 protein alone, or with coincubation of HDL3, 200 microg/ml, and AsA, 20
      microg/ml, at 37 degrees C for up to 24 h. As a control, the same amount of
      control LDL protein was added to PBS. The protective effects of the HDL3 and AsA
      were examined by both electrophoresis and determination of the lipid
      hydroperoxide (LPO) level in each sample. The concentration of AsA was also
      measured in samples containing AsA. The coincubation of HDL3 and AsA exerts more
      powerful anti-peroxidative effects against copper-catalyzed LDL peroxidation,
      than either of these agents alone. In addition, AsA was retained in the media by
      the addition of HDL3. The findings suggest that there are strong synergistic anti
      peroxidative effects of HDL3 and AsA and these two may act in concert in vivo to
      inhibit LDL peroxidation and thus exert an anti-atherosclerotic effect.

PMID- 9630695
TI  - An intermediate conductance K+ channel in the cell membrane of mouse intestinal
      smooth muscle.
AB  - Single channel currents were recorded from cell-attached and inside-out patches
      in smooth muscle cells of the mouse ileum in order to identify TEA-sensitive Ca2+
      dependent K+ channels. Cells were bathed in high-K+ (150 mM) solution with [Ca2+]
      buffered to 80-150 nM with EGTA and patch pipettes were filled with low-K+ (2.5
      mM) physiological solution. Two distinct TEA-sensitive unitary outward current
      levels were identified at a holding potential (Vh) of 0 mV, corresponding to
      intermediate conductance (IK, approximately 40 pS) and large conductance (BK,
      >200 pS) K+ channels. The open probability (Po) of IK channels increased with
      depolarization, the voltage for half-maximal activation averaging +12 mV in 80 nM
      Cabath2+. Raising the [Ca2+] in the high-K+ solution from 80 nM to 150 nM
      increased the Po of IK channels at Vh=0 mV from 0.078 to 0.21. Likewise, the open
      probability of BK channels at 0 mV was increased from 0.003 to 0.026. Unlike BK
      channels, IK channels inactivated with maintained depolarization with a voltage
      for half-maximal inactivation of -66 mV. IK channels were blocked by 2-5 mM
      external TEA and were sensitive to both charybdotoxin (100 nM) and apamin (500
      nM). Our results suggest that IK channels contribute significantly to the Ca2+
      dependent K+ conductance in visceral smooth muscle.

PMID- 9630696
TI  - Effects of docosahexaenoic (22:6n-3), tetracosapentaenoic (24:5n-3) and
      tetracosahexaenoic (24:6n-3) acids on the desaturation and elongation of n-3
      polyunsaturated fatty acids in trout liver microsomes.
AB  - The effects of long chain n-3 polyunsaturated fatty acids (PUFA) on the
      desaturation and elongation systems involved in the conversion of 18:3n-3 to
      24:6n-3 were investigated. Microsomes were prepared from the livers of rainbow
      trout and incubated with 14C-labelled 18:3n-3 and cofactors required for
      elongation and/or desaturation in the presence of 22:6n-3, 24:5n-3 or 24:6n-3.
      The formation of 24:6n-3 was significantly inhibited in the presence of 50 microM
      22:6n-3, 24:5n-3 or 24:6n-3, whereas the amount of radiolabelled 20:5n-3 formed
      was inhibited by only 24:5n-3 or 24:6n-3 at the same concentration. When malonyl
      CoA was omitted from the incubation system to allow the measurement of
      desaturation in the absence of elongation, the Delta6 desaturation of 14C-18:3n-3
      to 14C-18:4n-3 was inhibited by approximately 25% in the presence of 24:5n-3 or
      24:6n-3 but was not affected by 22:6n-3. The Delta5 desaturation of 14C-20:4n-3
      was not affected by the presence of any of the long chain PUFA and no significant
      effect of 18:3n-3, 22:6n-3 or 24:6n-3 on the Delta6 desaturation of 24:5n-3 to
      24:6n-3 was observed. To permit the measurement of individual elongation
      reactions, KCN was included in the incubation medium to inhibit desaturation and
      14C-labelled 18:3n-3, 18:4n-3, 20:4n-3, 20:5n-3 and 22:5n-3 were examined as
      substrates. 18:4n-3 and 22:5n-3 were more extensively used for elongation than
      18:3n-3, 20:4n-3 and 20:5n-3. The presence of 22:6n-3, 24:5n-3 or 24:6n-3 in the
      incubation system had no effect on any of the specific elongations of any of the
      substrates examined. It is concluded that, in the conversion of 18:3n-3 to 24:6n
      3 by trout liver microsomes, the Delta6 desaturation of 18:3n-3 may be subjected
      to direct feedback inhibition and that 24:5n-3 may be preferred over 18:3n-3 as a
      substrate for Delta6 desaturation.

PMID- 9630697
TI  - Spermidine, a polyamine site agonist, attenuates working memory deficits caused
      by blockade of hippocampal muscarinic receptors and mGluRs in rats.
AB  - Spermidine, an agonist of the polyamine site on the NMDA receptor/channel
      complex, did not affect the number of errors (attempts to pass through two
      incorrect panels of the three panel-gates at four choice points) in the working
      memory task with a three-panel runway setup, when injected bilaterally at 1 or 10
      microg/side into the dorsal hippocampus. Intrahippocampal administration of the
      muscarinic receptor antagonist scopolamine (3. 2 microg/side) significantly
      increased the number of working memory errors. The increase in working memory
      errors by intrahippocampal 3. 2 microg/side scopolamine was significantly reduced
      by concurrent infusion of 10 microg/side spermidine. Likewise, spermidine (10
      microg/side) was effective in attenuating the increase in working memory errors
      induced by intrahippocampal administration of AIDA (3. 2 microg/side), a potent
      and selective antagonist of the class I metabotropic glutamate receptor (mGluR).
      These results suggest that enhanced NMDA function via polyamine modulatory site
      on the NMDA receptor/channel can compensate dysfunction of hippocampal
      cholinergic and mGluR-mediated neurotransmission involved in working memory
      function.

PMID- 9630698
TI  - Contribution of the glycine site of NMDA receptors in rostral and intermediate
      caudal parts of the striatum to the regulation of muscle tone in rats.
AB  - The aim of the present study was to assess the contribution of the glycine site
      of NMDA receptors in the striatum to the regulation of muscle tone. Muscle tone
      was examined using a combined mechanoand electromyographic method, which measured
      simultaneously the muscle resistance (MMG) of the rat's hind foot to passive
      extension and flexion in the ankle joint and the electromyographic activity (EMG)
      of the antagonistic muscles of that joint: gastrocnemius and tibialis anterior.
      Muscle rigidity was induced by haloperidol (2.5 mg/kg i.p.). 5,7
      dichlorokynurenic acid (5,7-DCKA), a selective glycine site antagonist, injected
      in doses of 2.5 and 4.5 microg/0.5 microl bilaterally, into the rostral region of
      the striatum, decreased both the haloperidol-induced muscle rigidity (MMG) and
      the enhanced electromyographic activity (EMG). 5,7-DCKA injected bilaterally in a
      dose of 4.5 microg/0.5 microl into the intermediate-caudal region of the striatum
      of rats not pretreated with haloperidol had no effect on the muscle tone. The
      present results suggest that blockade of the glycine site of NMDA receptors in
      the rostral part of the striatum may be mainly responsible for the
      antiparkinsonian action of this drug.

PMID- 9630699
TI  - Aluminum alters intracellular calcium homeostasis in vitro.
AB  - The present paper reports data regarding the influence of aluminum, at micromolar
      concentrations, on intracellular calcium homeostasis. Al3+ modifies Ca2+ uptake
      in the endoplasmic reticulum (ER), accelerates Ca2+ release from mitochondria and
      strongly inhibits Ca2+-ATPase activity with a consequent high-level calcium
      accumulation inside the cell. These results suggest that Al3+ neurotoxicity may
      be related to an alteration of the intracellular calcium regulatory system.

PMID- 9630700
TI  - Topographical and quantitative assessment of white matter injury following a
      focal ischaemic lesion in the rat brain.
AB  - Axonal injury following cerebral ischaemia has attracted less attention than
      damage in grey matter. However, it is becoming increasingly recognised that axons
      are highly vulnerable to focal ischaemia [D. Dewar, D.A. Dawson, Changes of
      cytoskeletal protein immunostaining in myelinated fibre tracts after focal
      cerebral ischaemia in the rat, Acta. Neuropathol., 93 (1997) 71-77] [2]; [L.
      Pantoni, J.H. Garcia, J.A. Gutierrez, Cerebral white matter is highly vulnerable
      to ischemia, Stroke, 27 (1996) 1641-1647] [10]; [P. S. Yam, T. Takasago, D.
      Dewar, D.I. Graham, J. McCulloch, Amyloid precursor protein accumulates in white
      matter at the margin of a focal ischaemic lesion, Brain Res., 760 (1997) 150-157]
      [15]. Since white matter does not contain neuronal cell bodies or synapses it is
      likely that the mechanisms of injury and strategies for its protection are
      different from those in grey matter. In order that the effect of therapeutic
      intervention on the protection of axons can be assessed, a method by which axonal
      injury can be mapped and quantified is required. For this purpose, we
      investigated immunocytochemical methods using amyloid precursor protein (APP)
      following permanent middle cerebral artery occlusion in the rat. APP is
      transported by fast anterograde axonal transport [E.H. Koo, S.S. Sisodia, D.R.
      Archer, L.J. Martin, A. Weidemann, K. Beyreuther, P. Fischer, C.L. Masters, D.L.
      Price, Precursor of amyloid protein in Alzheimer disease undergoes fast
      anterograde axonal transport, Proc. Natl. Acad. Sci. U.S.A. 87 (1990) 1561-1565]
      [7] and has been shown to accumulate following a variety of insults to axons,
      indicative of dysfunction of axonal transport [R.N. Kalaria, S.U. Bhatti, E.A.
      Palatinsky, D.H. Pennington, E.R. Shelton, H.W. Chan, G. Perry, W.D. Lust,
      Accumulation of the beta amyloid precursor protein at sites of ischemic injury in
      rat brain, Neuroreport, 4 (1993) 211-214] [4]; [T. Kawarabayashi, M. Shoji, Y.
      Harigaya, H. Yamaguchi, S. Hirai, Expression of APP in the early stage of brain
      damage, Brain Res., 563 (1991) 334-338] [5]; [N. Otsuka, M. Tomonaga, K. Ikeda,
      Rapid appearance of beta-amyloid precursor protein immunoreactivity in damaged
      axons and reactive glial cells in rat brain following needle stab injury, Brain
      Res., 568 (1991) 335-338] [9]; [K. Shigematsu, P. L. McGeer, Accumulation of
      amyloid precursor protein in neurons after intraventricular injection of
      colchicine, Am. J. Pathol., 140 (1992) 787-794] [12]. We have been able to map
      the topographical relationship between APP accumulation and region of infarction
      using immunocytochemistry and image analysis techniques. Additionally, using a
      semi-quantitative scoring system, we have demonstrated that there is a
      relationship between the amount of APP accumulation and the volume of infarction
      following middle cerebral artery occlusion. These methods will be useful in the
      future for the assessment of therapeutic interventions on the protection of axons
      following ischaemic injury.

PMID- 9630701
TI  - Secondary structure of P-glycoprotein investigated by circular dichroism and
      amino acid sequence analysis.
AB  - P-glycoprotein (Pgp) is a plasma membrane protein known as an ATP-dependent drug
      efflux pump that confers multidrug resistance to tumor cells. Structural analysis
      of Pgp was investigated by circular dichroism (CD) for the first time and in
      combination with amino acid sequence analysis. CD of highly purified Pgp from
      human, rat and murine Pgp-overexpressing drug resistant cells revealed slight
      variations in the spectral shape when recorded in the presence of dodecyl
      maltoside (DM). These species-dependent variations in CD shapes resulted from the
      interaction of the oligosaccharidic part with the protein core since they were
      abolished either in the presence of sodium dodecyl sulfate (SDS) or after
      deglycosylation, the latter not altering the Pgp ATP-dependent drug transport
      activity. Whatever the level of Pgp glycosylation and the detergent used (SDS or
      DM), the content in secondary structure deduced from deconvolution of CD spectra
      is almost the same for the three sources of Pgp and estimated to 43% alpha-helix,
      16% beta-sheet, 15% beta-turn and 26% of other structures. These data, which
      constitute the first report of Pgp structure analysis by circular dichroism, are
      consistent with the 48% alpha-helix and 16% beta-sheets global contents predicted
      by using recently reported efficient secondary structure prediction methods. This
      consistency reinforces the reliability of the probable nature and localization of
      predicted Pgp secondary structure elements. This provides a good framework for
      precise 3D structure modeling of Pgp by homology with proteins of known 3D
      structure, as it is illustrated here for the A motifs of the ATP-binding domains
      of Pgp.

PMID- 9630702
TI  - Interfacial activation, lysophospholipase and transacylase activity of group VI
      Ca2+-independent phospholipase A2.
AB  - The Group VI 80-kDa Ca2+-independent phospholipase A2 (iPLA2) has been purified
      from murine P388D1 macrophages and Chinese hamster ovary (CHO) cells. The amino
      acid sequence of the iPLA2 has been determined and shown to contain a lipase
      consensus sequence and eight ankyrin repeats, which makes it distinct from Group
      I-V PLA2s. This enzyme appears to play a key role in mediating basal phospholipid
      remodeling. We now report that the Group VI iPLA2 displays interfacial activation
      toward short chain phospholipids, 1-octanoyl-2-heptanoyl-sn-glycero-3
      phosphocholine, 1,2-diheptanoyl-sn-glycero-3-phosphocholine, and 1,2-dihexanoyl
      sn-glycero-3-phosphocholine micelles. ATP protects the iPLA2 from a loss in
      activity as a result of prolonged incubation during the assay. Hence higher
      enzyme activity is observed in the presence than in the absence of ATP. Similar
      protection was obtained with glycerol. In addition, the iPLA2 exhibits multiple
      activities which are strongly dependent on substrate presentation. The
      lysophospholipase activity of this enzyme was diminished by Triton X-100 and
      stimulated by glycerol. With the combination of 50 microM Triton X-100 and 50%
      glycerol, the enzyme's lysophospholipase activity achieved equivalent activity to
      its PLA2 activity. The iPLA2 displayed both lysophospholipid/transacylase and
      phospholipid/transacylase activity, supporting the conclusion that the mechanism
      of action of iPLA2 proceeds through an acyl-enzyme intermediate as proposed for
      the Group IV cPLA2.

PMID- 9630703
TI  - Oxidative degradation of polyamines in rat pancreatic hypertrophy.
AB  - In the hypertrophic pancreas, we studied the oxidative degradation of polyamines,
      which are endogenous polycations important for cell division, growth and
      differentiation. To induce pancreatic hypertrophy, rats were fed on a semi
      synthetic diet containing a daily dose of 42 mg phytohaemagglutinin per rat for 5
      or 10 days. In the model, the activities of polyamine oxidase (the enzyme that
      degrades spermidine, spermine and mainly their acetyl derivatives) and diamine
      oxidase (the key enzyme of terminal catabolism of polyamines in vivo) increased
      by 100-180% and 90-100%, respectively, parallel to an elevation in polyamine
      content (40-100%). The results suggest that in pancreas hypertrophy, which does
      not exhibit stimulation of spermidine/spermine N1-acetyltransferase activity,
      increases in the activity of polyamine and diamine oxidases are related events
      that lead to putrescine formation and removal of excess polyamines.

PMID- 9630704
TI  - Differential temporal expression of mRNAs for ciliary neurotrophic factor (CNTF),
      leukemia inhibitory factor (LIF), interleukin-6 (IL-6), and their receptors
      (CNTFR alpha, LIFR beta, IL-6R alpha and gp130) in injured peripheral nerves.
AB  - The mRNA expression of the neuropoietic cytokines, ciliary neurotrophic factor
      (CNTF), leukemia inhibitory factor (LIF), interleukin-6 (IL-6), and their
      receptor components (CNTFRalpha, LIFRbeta, IL-6Ralpha and gp130) was examined in
      peripheral nerves after two different types of injury, crush and transection. The
      CNTF mRNA expression levels decreased after injury and remained low in the
      transected model, but recovered in 4 weeks in the crushed model. The LIF mRNA
      rapidly increased after damage and returned gradually to control levels. The IL-6
      mRNA expression increased rapidly within 1 day after injury but dramatically
      decreased soon after. The CNTFRalpha mRNA levels gradually increased after nerve
      injury. LIFRbeta was expressed in the intact nerve and decreased slightly after
      injury. The IL-6Ralpha expression was observed faintly in the intact nerve and
      increased significantly soon after injury. There was also an increase in the
      expression of gp130. Although the temporal expression of these neuropoietic
      cytokines and receptors was extremely different, their pattern was similar
      between the crushed and transected models, except for CNTF. These results suggest
      that the expression of the ligands and receptors are differentially regulated
      after peripheral nerve injury, implying that each cytokine and signal
      transduction system has entirely distinctive functions in neuronal regeneration
      and repair.

PMID- 9630705
TI  - Multiple neuroanatomical tracing in primates.
AB  - The present report deals with a multiple tract-tracing procedure in non-human
      primates enabling the simultaneous visualization of retrogradely transported
      Fluoro-Gold (FG) and cholera toxin B subunit (CTB) in combination with
      anterogradely transported biotinylated dextran amine (BDA). Two issues have
      played key roles on the achievement of this reliable procedure: first, the recent
      development of a commercial antiserum against FG that allows us to convert the
      original fluorescent signal of this dye in a permanent precipitate via standard
      peroxidase-anti-peroxidase methods; second, the introduction of the novel
      peroxidase substrate Vector(R) VIP (V-VIP), resulting in a purple precipitate.
      The combination of these neuroanatomical tracers in one and the same histological
      section opens a possibility for the permanent visualization of the convergence of
      inputs from a particular brain area onto identified, two different subsets of
      projection cells of another area. Furthermore, this combination of three tracers
      emerges as a powerful technical tool for obtaining broad amounts of complementary
      data regarding the monkey brain connectivity, thus significantly reducing the
      number of animals needed to complete a particular study.

PMID- 9630706
TI  - Action of the allelochemical, fischerellin A, on photosystem II.
AB  - The cyanobacterium, Fischerella muscicola, produces a secondary metabolite named
      fischerellin A (FS) that strongly inhibits the growth of cyanobacteria and other
      photosynthetic organisms. The compound exhibits a unique structure and is
      composed of two cyclic amines and a C15 substituent that contains a double bond
      in the (Z) configuration and two triple bonds [L. Hagmann, F. Juttner,
      Tetrahedron Lett., 37 (1996) 6539-6542]. The site of FS action is located in
      photosystem II (PSII). The chlorophyll fluorescence induction transient and O2
      evolution methods have been used to determine the site of action of FS in PSII.
      FS affects the fluorescence transients, as well as O2 evolution by the
      cyanobacterium, Anabaena P9. The green alga, Chlamydomonas reinhardtii, and
      higher plants were also affected by FS in a concentration- and time-dependent
      fashion. FS acts at several sites which appear with increasing half-time of
      interaction in the following sequence: (1) effect on the rate constant of QA-
      reoxidation; (2) primary photochemistry trapping; (3) inactivation of PSII
      reaction center; and (4) segregation of individual units from grouped units. FS
      does not affect the photosynthetic activity of purple bacteria, Rhodospirillum
      rubrum.

PMID- 9630707
TI  - Decreased membrane fluidity and unsaturated fatty acids in Niemann-Pick disease
      type C fibroblasts.
AB  - Niemann-Pick disease type C (NP-C) is an autosomal recessive disorder
      characterized by the sequestration and trapping of endocytosed cholesterol in
      lysosomes. The NPC1 gene on chromosome 18 was recently identified but its
      physiological function remains unknown. We have studied the lipid compositions of
      cultured human NP-C fibroblasts and mouse SPM-3T3 cell line derived from the
      C57BL/KsJ NP-C model mouse, which belongs to the same complementation group.
      Fibroblasts derived from apparently normal age-matched individuals and a subline
      of SPM-3T3 cells which restores cholesterol metabolism by transfer of human
      chromosome 18 were used as controls. Levels of free cholesterol in whole cell
      homogenates increased about 1.5-fold in human NP-C fibroblasts and mouse SPM-3T3
      cells, while in the plasma membrane, cholesterol content did not significantly
      change in NP-C fibroblasts but rather decreased in SPM-3T3 cells. The total
      phospholipid content did not significantly change; however, among phospholipid
      head groups, increases in sphingomyelin and decreases in other classes were
      observed in human NP-C fibroblasts and mouse SPM-3T3 cells. The ratios of
      saturated fatty acids to unsaturated fatty acids increased in both human and
      mouse cells. The increase was also confirmed in the plasma membrane fraction of
      SPM-3T3 cells. Membrane fluidity was examined using a 1,6-diphenyl-1,3,5
      hexatriene (DPH) fluorescent probe. The DPH anisotropy values were markedly
      increased in NP-C fibroblasts and in SPM-3T3 cells. The results suggest that a NP
      C mutation causes complex alterations in cellular lipid contents and biophysical
      properties of the membrane.

PMID- 9630708
TI  - Developmental regulation of decorin expression in postnatal rat brain.
AB  - Here, we report on the expression of the small chondroitin/dermatan sulfate
      proteoglycan decorin in the developing postnatal rat brain. Northern analysis of
      brain RNA demonstrated decorin transcripts with peak expression on postnatal day
      3 followed by a slow decline to the lower adult level. In situ hybridization and
      immunohistochemistry revealed postnatal decorin expression in the grey matter of
      neocortex, hippocampus and thalamus, in myelinated fibre tracts and in several
      mesenchymal tissues (blood vessels, pia mater and the choroid plexus). In the
      neocortex, decorin is expressed in a specific laminar pattern with intense
      staining of the cortical plate and its derivatives, which differs remarkably from
      the distributions observed for other proteoglycans [B. Miller, A.M. Sheppard,
      A.R. Bicknese, A.L. Pearlman, Chondroitin sulfate proteoglycans in the developing
      cerebral cortex: the distribution of neurocan distinguishes forming afferent and
      efferent axonal pathways, J. Comp. Neurol. 355 (1995) 615-28]. Thus, decorin
      seems to serve yet unknown functions in the developing rat brain parenchyma in
      addition to its well-established role as a constituent of the mesenchymal
      extracellular matrix.

PMID- 9630709
TI  - Transport of side-chain oxidized oxysterols in the human circulation.
AB  - To study the transport of 24-hydroxycholesterol, 27-hydroxycholesterol and 3beta
      hydroxy-5-cholestenoic acid in the circulation, the distribution of these
      oxysterols was determined in plasma, very low density lipoprotein, low density
      lipoprotein, high density lipoprotein, and lipoprotein-free plasma. An accurate
      method based on isotope dilution-mass spectrometry with use of individual
      deuterium labeled internal standards was used. 24-Hydroxycholesterol and 27
      hydroxycholesterol were found to be associated mainly with HDL and LDL, whereas
      3beta-hydroxy-5-cholestenoic acid was found predominantly in the lipoprotein-free
      fraction. While both 24-hydroxycholesterol and 27-hydroxycholesterol are present
      mainly in esterified form in plasma, 3beta-hydroxy-5-cholestenoic acid was
      present as free acid only. For reasons of comparison, a number of other
      oxysterols were determined in plasma and in isolated lipoprotein fractions.
      Significant amounts of these oxysterols were formed by cholesterol autoxidation
      during fractionation of plasma. It was therefore not possible to calculate the
      distribution of these oxysterols in the different plasma fractions. The present
      results are consistent with our previous finding that the less polar cholesterol
      metabolite 27-hydroxycholesterol competes with cholesterol for transport out of
      cells using HDL as an acceptor molecule, whereas the transport of the more polar
      compound 3beta-hydroxy-5-cholestenoic acid is facilitated by albumin.

PMID- 9630710
TI  - Induction of NADPH-diaphorase activity in the rat periaqueductal gray matter
      after nociceptive visceral stimulation.
AB  - Nitric oxide (NO) is a neuronal messenger that it is thought to be involved in
      the nociceptive transmission modulation. The activity of nicotinamide adenine
      dinucleotide phosphate diaphorase (NADPH-d) was shown to be identical to NOS
      activity in the brain. Since the periaqueductal gray matter (PAG) plays an
      important role in pain perception and antinociception this study was carried out
      to monitor the expression of NADPH-d in PAG after nociceptive visceral
      stimulation. Our data showed that the noxious visceral stimulation significantly
      increased NADPH-d positive neurons and that these neurons were localized in the
      ventrolateral areas of the PAG. These findings suggest that NO in the PAG may
      play a role in pain modulation and antinociception.

PMID- 9630711
TI  - Highly sensitive ELISA-based assay for quantifying protein levels in neuronal
      cultures.
AB  - A simple assay for quantifying the expression level of proteins in situ is
      presented. The assay is performed directly in culture plates and simply requires
      incubating the cells (either fixed or in live cultures) with the appropriate
      antibody against the desired protein. Cells are then incubated with a peroxidase
      conjugated secondary antibody followed by incubation with the soluble peroxidase
      substrate-tetramethylbenzidine. Antibody binding levels are quantified in an
      ELISA-based protocol by reading optical density at 450 nm. The assay is
      applicable for any surface-attached cell culture. The assay is highly sensitive,
      allowing detection of expressed proteins in a monolayer of cell cultured in a 96
      well plate. The assay was optimized for a neuronal cell-line-P19. These are
      embryonal carcinoma cells which differentiate into neurons after treatment with
      retinoic acid. The neurons do not survive well in 96 well plates and are thus
      plated in 24 or 48 well plates. We demonstrate the use of the method for an in
      vivo labeling of neurons by quantifying epitopes which are exposed upon nerve
      stimulation. Advantages of a routine ELISA protocol in quantification over wide
      range of sensitivity and in performing simultaneous large number of repetitions
      and different controls are thus fully extended to live cell cultures.

PMID- 9630712
TI  - Calyculin A modulates the kinetic constants for the Na+-coupled taurine transport
      in Ehrlich ascites tumour cells.
AB  - The effect of the phosphatase inhibitor calyculin A (cal A) on the kinetic
      parameters of the Na+-coupled taurine uptake via the taurine transporter in the
      Ehrlich ascites tumour cells has been investigated. Preincubation with cal A (100
      nM) reduces the initial taurine influx by about 20%, but has no effect on the
      diffusional component of the taurine influx or on the taurine release from cells
      suspended in isotonic or in hypotonic medium. Thus, cal A-sensitive phosphatases
      only affect taurine transport mediated by the Na+-dependent taurine transporter.
      Cal A increases the Michaelis-Menten constant for binding of taurine to the
      transporter from 31+/-6 to 45+/-4 microM and reduces the taurine transport
      capacity from 210+/-20 to 170+/-10 nmol x g dry wt(-1) x min(-1) [corrected]. The
      Michaelis-Menten constant for binding of Na+ to the taurine transporter is
      concomitantly increased from 96+/-11 to 129+/-8 mM and the Na+:taurine coupling
      ratio for activation of the transport cycle is reduced from 3.3+/-0.6 to 2.4+/
      0.2. This suggests that cal A-sensitive phosphatases maintain a high affinity of
      the taurine transporter towards Na+ and taurine as well as a high taurine
      transport capacity in unpertubated Ehrlich cells.

PMID- 9630714
TI  - Infrared spectroscopic identification of the C-O stretching vibration associated
      with the tyrosyl Z. and D. radicals In photosystem II 
AB  - Photosystem II (PSII) is a multisubunit complex, which catalyzes the photo
      induced oxidation of water and reduction of plastoquinone. Difference Fourier
      transform infrared (FT-IR) spectroscopy can be used to obtain information about
      the structural changes accompanying oxidation of the redox-active tyrosines, D
      and Z, in PSII. The focus of our work is the assignment of the 1478 cm-1
      vibration, which is observable in difference infrared spectra associated with
      these tyrosyl radicals. The first set of FT-IR experiments is performed with
      continuous illumination. Use of cyanobacterial strains, in which isotopomers of
      tyrosine have been incorporated, supports the assignment of a positive 1478/1477
      cm-1 mode to the C-O stretching vibration of the tyrosyl radicals. In negative
      controls, the intensity of this spectral feature decreases. The negative controls
      involve the use of inhibitors or site-directed mutants, in which the oxidation of
      Z or D is eliminated, respectively. The assignment of the 1478/1477 cm-1 mode is
      also based on control EPR and fluorescence measurements, which demonstrate that
      no detectable Fe+2QA- signal is generated under FT-IR experimental conditions.
      Additionally, the difference infrared spectrum, associated with formation of the
      S2QA- state, argues against the assignment of the positive 1478 cm-1 line to the
      C-O vibration of QA-. In the second set of FT-IR experiments, single turnover
      flashes are employed, and infrared difference spectra are recorded as a function
      of time after photoexcitation. Comparison to kinetic transients generated in
      control EPR experiments shows that the decay of the 1477 cm-1 line precisely
      parallels the decay of the D. EPR signal. Taken together, these two experimental
      approaches strongly support the assignment of a component of the 1478/1477 cm-1
      vibrational lines to the C-O stretching modes of tyrosyl radicals in PSII.
      Possible reasons for the apparently contradictory results of Hienerwadel et al.
      (1996) Biochemistry 35, 15,447-15,460 and Hienerwadel et al. (1997) Biochemistry
      36, 14,705-14,711 are discussed. Copyright 1998 Elsevier Science B.V. All rights
      reserved.

PMID- 9630713
TI  - Activation of protein kinase C by phorbol dibutyrate potentiates [3H]MK-801
      binding in rat brain slices.
AB  - Effects of activation of protein kinase C (PKC) on N-methyl-D-aspartate) NMDA
      receptor function were analyzed by quantitative autoradiography using [3H]MK-801
      in rat brain slices. The density of [3H]MK-801 binding was highest in hippocampus
      and high levels were found in cortex, striatum and thalamus. Levels in brainstem
      and molecular layer of cerebellum were low. The receptor binding was markedly
      decreased in almost all areas by addition of 2. 5 mM Mg2+. After activation of
      PKC by 100 nM phorbol-12, 13-dibutyrate (PDBu), [3H]MK-801 binding was increased
      in most areas, but binding levels were not changed in brainstem and cerebellum.
      The elevated [3H]MK-801 binding produced by PDBu was significantly inhibited by
      addition of Mg2+ except in inferior colliculus and cerebellum. These results
      suggest that activation of PKC potentiates NMDA receptor function in a region
      specific manner in the rat brain.

PMID- 9630715
TI  - Production of digoxigenin-labelled RNA probes and the detection of cytokine mRNA
      in rat spleen and brain by in situ hybridization.
AB  - Non-radioactive in situ hybridization is a sensitive method for determining the
      site of production for secretory molecules such as cytokines. We report here on
      the central and peripheral induction of proinflammatory cytokines by endotoxin,
      and outline procedures for the generation and application of rat-specific
      digoxigenin (Dig)-labelled RNA probes for the localization of mRNA by in situ
      hybridization. Rats were injected either intravenously (i.v.) or
      intracerebroventricularly (i.c.v.) with vehicle or lipopolysaccharide (LPS) and
      sacrificed at various time intervals post-injection. Rats were then perfused with
      4% paraformaldehyde and the spleens and brains were removed and cryoprotected in
      30% sucrose. Dig-labelled, rat-specific, antisense and sense RNA probes were
      generated by in vitro transcription from PCR-derived templates. Positive staining
      with all the antisense probes was cytoplasmic, whereas the sense probes showed no
      staining. Numerous tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta
      (IL-1beta) mRNA positive cells were observed in the marginal zone and in the red
      pulp of the spleen after iv LPS injections, whereas sections from saline-treated
      animals showed minimal cytokine mRNA expression. Cells positive for TNF-alpha and
      IL-1beta mRNA were detectable in the brain after i.c.v. injections of LPS, but
      not after icv injection of vehicle. An antisense probe for c-fos was utilized in
      these studies as a positive control for our procedure due to its anatomically
      specific expression in the rat brain after LPS. In conclusion we have
      demonstrated that in situ hybridization with Dig-labelled RNA probes is an
      efficient, sensitive and reliable tool to localize cytokine mRNA production in
      rat tissue.

PMID- 9630716
TI  - Linoleic acid peroxidation by Solanum tuberosum lipoxygenase was activated in the
      presence of human 5-lipoxygenase-activating protein.
AB  - The present investigation describes the ability of human 5-lipoxygenase
      activating protein (FLAP) to activate a plant 5-lipoxygenase. The presence of an
      active recombinant human FLAP in the 100000xg membrane fraction of infected Sf9
      cells led to a specific increase in 9-hydroperoxyoctadecadienoic acid (9-HPOD)
      synthesis (+68%) or in 5-hydroperoxyeicosatetraenoic acid (5-HPETE) synthesis
      (+68%), after action of Solanum tuberosum tuber 5-lipoxygenase (S.t.LOX) on
      linoleic acid (natural plant lipoxygenase substrate) or on arachidonic acid. On
      the contrary, the presence of non-transfected membranes obtained from non
      infected Sf9 cells led to an inhibition of lipoxygenase activity. MK-886, a
      potent inhibitor of leukotriene biosynthesis, blocked the FLAP dependent S.t.LOX
      activation after preincubation with FLAP transfected membranes. In conclusion,
      this study demonstrates that a recombinant human FLAP can stimulate a
      lipoxygenase other than mammalian 5-lipoxygenase (S.t.LOX) by using different
      polyunsaturated fatty acids as substrates.

PMID- 9630717
TI  - Anandamide amidase inhibition enhances anandamide-stimulated nitric oxide release
      in invertebrate neural tissues.
AB  - Anandamide, an endogenous cannabinoid signaling molecule, in a concentration
      dependent manner, initiates the release of nitric oxide (NO) from leech and
      mussel ganglia. SR 141716A, a cannabinoid antagonist, blocks the anandamide
      stimulated release of NO from these tissues. Methyl arachidonyl fluorophosphonate
      (MAFP), a specific anandamide amidase inhibitor, when administered to either
      ganglia with anandamide (10-6 M) did not increase the peak level of NO release
      but did significantly extend NO release from 12 to 18 min (P<0.05). Lower levels
      of anandamide (10-8 and 10-7 M) do not stimulate the release of significant
      amounts of NO from these tissues. However, in the presence of MAFP (2.5 nM), the
      lower anandamide concentrations were able to release significant peak amounts of
      NO. In mussel neural tissues, the peak NO release increased from 2.2+/-1.3 nM to
      8.6+/-2.1 nM. Taken together, the results indirectly demonstrate the presence of
      anandamide amidase in these tissues, suggesting that the enzyme may serve as an
      endogenous regulator of anandamide action.

PMID- 9630718
TI  - A miniaturized monolayer trough with variable surface area in the square
      millimeter range.
AB  - A new simple concept for a miniaturized monolayer trough is described. The
      overall monolayer area in the expanded state is approximately 150 mm2 and can be
      reduced by a factor of 2. The surface area is a function of the shape of the
      meniscus formed by the subphase and is controlled by the amount of water in the
      monolayer trough. The controlled compression of monolayers to a desired area per
      molecule with simultaneous observation of the lateral distribution of
      fluorescently labeled molecules is shown. A biological reaction between a
      specific antibody and lipid anchored peptide demonstrates the feasibility of
      monolayer experiments, which require only very small quantities of substance (in
      the pmol range). This trough might also be a valuable tool for the 2D
      crystallization of proteins at lipid layers via specific binding sites such as
      metal chelators.

PMID- 9630719
TI  - The medial preoptic and anterior hypothalamic regions of the rhesus monkey:
      cytoarchitectonic comparison with the human and evidence for sexual dimorphism.
AB  - Examination of thionin-stained sections through the hypothalamus of the rhesus
      monkey revealed nuclei that resemble the first, second and third interstitial
      nuclei of the anterior hypothalamus (INAH1-3) of the human. Volumetric analysis
      of these nuclei in a small sample of monkeys suggests that the nucleus that
      resembles INAH3 is larger in males than in females. INAH1-3 have each been
      reported to be larger in men than in women and each has been considered as a
      potential candidate for homology with the much-studied sexually dimorphic nucleus
      of the preoptic area (SDN-POA) of the rat. Positional and cytoarchitectonic
      criteria suggest that of these nuclei, INAH3 and its potential counterpart in the
      rhesus monkey are the best candidates for homology with the SDN-POA. While the
      criteria employed in the present study may be used to suggest homologies, they
      are not adequate to confirm them. Confirmation of the homologies suggested here
      must rely on other considerations such as connectivity, neurotransmitter and
      peptide content, and function. It is hoped that the present report will stimulate
      interest in further examinations of the rhesus hypothalamus that will test both
      the suggested homologies and the evidence for sexual dimorphism.

PMID- 9630720
TI  - Docosahexaenoic acid (DHA) alters the structure and composition of membranous
      vesicles exfoliated from the surface of a murine leukemia cell line.
AB  - Membrane lipid microdomains are regions of the membrane thought to be
      functionally important, but which have remained poorly characterized because they
      have proven to be difficult to isolate. The exfoliation of small membranous
      vesicles from the cell surface is a continuous and normal activity in many cells.
      If microdomains are relatively large or stable, they may influence the structure
      and composition of exfoliated vesicles, which are easy to isolate. We tested the
      ability of docosahexaenoic acid (DHA), a fatty acid proposed to alter the
      structure of microdomains, to change the structure and composition of vesicles
      exfoliated from a murine leukemia cell line. Cells were cultured in normal and
      DHA-enriched media for 72 h, then washed and given a 15-h exfoliation period.
      Afterwards, the pooled vesicles and their parent plasma membrane were collected
      and analyzed. Vesicles and plasma membrane from cells grown in normal culture
      medium had similar fatty acid compositions, including equal, and low, proportions
      of DHA, but the vesicles had much more cholesterol and displayed higher
      anisotropy than the plasma membrane. When cells were grown in DHA-enriched
      medium, both the plasma membrane and exfoliated vesicles had 10-fold elevated
      levels of DHA in their phospholipids, with the DHA displacing other
      polyunsaturates. These cells released vesicles having significantly reduced
      levels of cholesterol and monoenoic fatty acids than those in normal culture. The
      anisotropy of these vesicles was also dramatically reduced. These data are
      consistent with DHA altering the structure and composition of membrane
      microdomains on the cell surface, and suggest that exfoliated vesicles may prove
      useful in the further study of membrane microdomains.

PMID- 9630721
TI  - MgATP has different inhibitory effects on the use of 1-acyl
      lysophosphatidylcholine and lyso platelet-activating factor acceptors by neuronal
      nuclear acetyltransferase activities.
AB  - The inhibitory effects of MgATP on neuronal nuclear acetyltransferase activities
      were studied using lyso platelet-activating factor (lyso-PAF, 1-alkyl-sn-glycero
      3-phosphocholine) and lysophosphatidylcholine (lyso-PC, 1-acyl-sn-glycero-3
      phosphocholine). The nuclear (N1) acetylation of lyso-PC was more profoundly
      inhibited by MgATP. MgATP did not alter the apparent Km for acetyl-CoA in either
      acetylation reaction. The inhibitory effects of MgATP were not seen for other
      nucleotides or MgAMP-PCP. Kinase inhibitors such as staurosporine (1 microM),
      chelerythrine, and R59022 (diglyceride kinase inhibitor I) did not block the
      MgATP inhibition of either acetylation. However, the addition of phospholipids to
      the assays indicated a selective inhibitory effect for PIP (25-50 microM) in the
      nuclear acetylation of lyso-PAF. When N1 was incubated with [gamma-33P]ATP,
      phosphatidic acid and PIP were the principal radioactive lipid products. While
      the extent of MgATP inhibition of lyso-PAF acetylation was similar at different
      concentrations of lyso-PAF, increasing lyso-PC concentrations greatly decreased
      the MgATP inhibition seen in lyso-PC acetylations. Nuclear envelopes prepared in
      the presence of PMSF, and fraction N1 exposed to PMSF, did not show the
      inhibitory effect of MgATP on lyso-PC acetylation. PMSF (an inhibitor of certain
      phospholipase and lysophospholipase activities) did not reduce the MgATP
      inhibition of lyso-PAF acetylation. Arachidonoyl trifluoromethylketone, an
      inhibitor of cytosolic phospholipases A2 and of lysophospholipase activity
      associated with cPLA2, also blocked the inhibitory effect of MgATP on lyso-PC
      acetylation. Using radioactive lyso-PC substrate, fraction N1 produced labeled
      free fatty acid and phosphatidylcholine. In the presence of acetyl-CoA, the
      production of radioactive phosphatidylcholine increased almost 6-fold when MgATP
      was also included in these incubations. In the presence of MgATP and acetyl-CoA,
      PMSF reduced the levels of radioactive free fatty acid and phosphatidylcholine
      derived from lyso-PC, while Triacsin C, an inhibitor of acyl CoA synthetase,
      decreased phosphatidylcholine labeling. These findings suggest that MgATP
      inhibition of lyso-PC acetylation results from a loss of lyso-PC substrate that
      is largely mediated by nuclear lysophospholipase, acyl-CoA synthetase and lyso-PC
      acylation. Thus the neuronal nuclear production of Acyl PAF may be regulated by
      paths that compete for the lyso-PC substrate. In contrast, the acetylation of
      lyso-PAF is inhibited by PIP, a product of nuclear PI kinase reactions.

PMID- 9630722
TI  - Separation of a process from the neuronal cell body using a thin aluminum foil
      separator.
AB  - A new technique using a simple-structured separator is described to separate the
      end of the process from the cell body (soma) of cultured cells. By this method,
      stimulation limited to neuronal processes is experimentally possible. The
      separator is of an oblong shape and consists of two parts: a square bracket
      shaped frame made of Teflon and a thin aluminum foil which is stuck on both free
      ends of frame (bracket) coated with epoxy-resin. The separator is horizontally
      placed on the dish under microscope to divide the process on the way, so that the
      free end of the process is outside the oblong separator. This separator is simple
      and low cost, and does not need a long process, unlike other methods requiring a
      special culture dish with a micro-groove for growth of the neuronal process
      (neurite). The new technique could be useful in basic pain research and
      neurophysiology.

PMID- 9630723
TI  - The influence of structural-dynamic organization of RC from purple bacterium
      rhodobacter sphaeroides on picosecond stages of photoinduced reactions 
AB  - Effects of the hydrogen bond network on the rate constants of energy migration
      (km), charge separation (ke), electron transfer to QA (kQ) and P+I- recombination
      in RC of Rhodobacter sphaeroides were analysed in control and modified RC
      preparations at different temperatures. Modification of RC were made by the
      addition of 40% v/v DMSO. The rate constants km, ke, kQ were evaluated from pump
      and-probe measurements of the absorption difference kinetics at 665 nm
      corresponding to BPhL- formation and subsequent electron transfer to QA. For the
      investigation of P+I- recombination a primary quinone acceptor was pre-reduced in
      the dark by adding of 1 mg/ml of dithionite and 1 mM sodium ascorbate.
      Recombination kinetics were measured at 665 and 870 nm. The numerical analysis of
      the temperature dependence of ke and kQ was performed on the basis of the model
      proposed by Kakitani and Kakitani (T. Kakitani and H. Kakitani (1981), Biochim.
      Biophys. Acta, 635, 498-514). It was found that: (a) in control samples the
      molecular rate constants km, ke and kQ were about (3.4 ps)-1, (4.5 ps)-1 and (200
      ps)-1, respectively; (b) under modification by DMSO these rates decrease up to
      (5.3 ps)-1, (10.3 ps)-1 and (500 ps)-1, respectively; (c) as the temperature
      drops from 300 K to 77 K the rate constant km decreases by 1.8 times in control
      and by 3.2 times in modified samples. In contrast to the observed km changes the
      increase in ke and kQ values by 2 and more times under cooling was found in
      control and modified RC; (d) in control preparations with QA acceptor pre-reduced
      in the dark the lowering of the temperature caused the increase in the time of
      P+I- recombination from 10 to 20 ns. After DMSO modification the kinetics of
      charge recombination in RC was biexponential at room temperature with tau=10 ns
      and tau1=0.8 ns, and at 77 K with tau=20 ns and tau1=0.6 ns, correspondingly. The
      results obtained reveal that in RC isolated from Rb. sphaeroides the processes of
      energy migration, charge separation, electron transfer to QA and ion-radical pair
      P+I- recombination depend on the state of hydrogen bonds of water-protein
      structure. Fast relaxation processes in RC structure including polarization of H
      containing molecules in the surrounding of electron carriers can accept electron
      energy dissipated at the initial steps of energy and electron transfer. Copyright
      1998 Elsevier Science B.V. All rights reserved.

PMID- 9630724
TI  - Characterization of swollen lamellar phase of dimyristoylphosphatidylcholine
      gramicidin A mixed membranes by DSC, SAXS, and densimetry.
AB  - For the fully hydrated multilamellar stack of dimyristoylphosphatidylcholine
      (DMPC) fluid membranes containing hydrophobic peptide gramicidin A (GrA), the
      membrane thickness and the bilayer-bilayer separation (i.e., water layer
      thickness) were determined by measuring small-angle X-ray scattering and the
      density of aqueous suspensions of DMPC-GrA mixtures. When the molar ratio of GrA
      to DMPC was 0.04, the membrane thickness decreased by 2-3 A by the incorporation
      of GrA molecules into DMPC bilayers, whereas the water layer thickness increased
      by 3-4 A. As the cause of the increment of water layer thickness, two
      possibilities were considered; (1) attractive van der Waals force acting between
      the bilayer membranes weakened by the decrease of membrane thickness, and (2)
      repulsive undulation force enhanced by the incorporation of GrA which may
      stabilize the gauche conformers of the lipid acyl chains.

PMID- 9630725
TI  - Phototransformation and proton pumping activity of the 14-fluoro
      bacteriorhodopsin derivatives.
AB  - The photoinduced behavior and proton pumping characteristics of some
      bacteriorhodopsin (BR) analogs with fluorinated chromophores (all-trans 14
      fluorinated [14-F] retinal and 13-cis 14-F retinal) derived from wild type (WT)
      and D96N mutant BR were investigated. These analogs were characterized using
      spectrophotometry and a highly sensitive electrochemical technique. Similar to
      the white membrane JW2N, the apomembranes WT ET 1000 and D96N form photoactive
      pigments with the 14-F chromophores. The resulting analogs have a major
      absorption band at 588 nm. Red-shifted pigment (lambdamax</=680 nm) has been
      previously observed as a minor component of the major 587-nm pigment in 14-F BR
      made with white membrane JW2N. A similar red-shifted pigment is formed under
      yellow light (lambda>500 nm) only in the 14-F analogs derived from WT ET 1000.
      The measurements of the photoinduced transformation in 14-F WT analogs show that
      the photocycle of the major pigment occurs simultaneously with the process in the
      red region and is partially masked by the formation of the red-shifted species.
      The 14-F D96N samples have a significantly slower and more complicated
      photoinduced behavior. Electrochemical measurements show that the photoinduced
      transformation of the red species is not accompanied by proton transport.

PMID- 9630726
TI  - Kinetics of electron and proton transfer to ubiquinone-10 and from ubiquinol-10
      in a self-assembled phosphatidylcholine monolayer.
AB  - Upon incorporating from 0.5 to 2 mol% ubiquinone-10 (UQ) in a self-assembled
      monolayer of dioleoylphosphatidylcholine (DOPC) supported by mercury, the
      kinetics of UQ reduction to ubiquinol-10 (UQH2) as well as that of UQH2 oxidation
      to UQ were investigated in borate buffers over the pH range from 8 to 9.5 by
      cyclic voltammetry. A general kinetic approach was adopted to interpret the
      dependence of the applied potential upon the scan rate at constant pH and upon pH
      at constant scan rate, while keeping the initial reactant concentration and the
      faradaic charge constant. The oxidation of UQH2 to UQ in DOPC monolayers occurs
      via the reversible release of one electron with formation of the semiubiquinone
      radical cation UQH2.+, followed by its rate-determining deprotonation by hydroxyl
      ions with formation of the UQH. neutral radical; the latter is then
      instantaneously oxidized to UQ. Analogously, the rate-determining step in UQ
      reduction to UQH2 consists in the protonation by hydrogen ions of the
      semiubiquinone radical anion UQ.- resulting from the reversible uptake of one
      electron by UQ. However, a non-negligible fraction of UQ.- uptakes protons very
      slowly, and hence, retains its intermediate oxidation state during the recording
      of the cyclic voltammetric peak for UQ reduction.

PMID- 9630728
TI  - Photoinduced electron transfer from carboxymethylated cytochrome c to
      plastocyanin.
AB  - Photoinduced electron transfer from cytochrome c to plastocyanin was investigated
      using a novel method. Reduced carboxymethylated cytochrome c (CmCyt c), with
      carbon monoxide bound to the heme iron, and oxidized plastocyanin were mixed. At
      1 mM CO the reduced state of CmCyt c is stabilized by about 350 meV. After flash
      photolysis of CO the apparent redox potential of CmCyt c drops resulting in
      electron transfer to plastocyanin. The electron transfer characteristics were
      investigated at approximately 30 different wavelengths in the range 390-460 nm. A
      global fit of the data showed that the electron transfer rate is 960+/-30 s-1 at
      pH 7.

PMID- 9630729
TI  - Reconstitution of the B800 bacteriochlorophylls in the peripheral light
      harvesting complex B800-850 of rhodobacter sphaeroides 2.4.1 with BChl a and
      modified (bacterio-)chlorophylls 
AB  - A method is described for reversibly removing bacteriochlorophyll from the B800
      site of the B850-850 antenna complex from Rhodobacter sphaeroides. This method
      uses the oligosaccharidic detergent Triton BG-10, together with an incubation at
      pH 5.0. Reconstitution at the B800-site has been successfully achieved for a
      range of modified bacteriochlorophylls. Copyright 1998 Elsevier Science B.V. All
      rights reserved.

PMID- 9630730
TI  - Multiple crystal types reveal photosystem II to be a dimer.
AB  - Three types of photosystem II (PS II) crystals have been produced using a variety
      of detergents. Intermediate stages of crystal formation were examined and it was
      determined that each crystal probably originates from a single grana membrane.
      Each crystal type was examined by electron microscopy and image processing,
      providing three different projection maps. The highest resolution results came
      from type 1 and type 2 crystals. Projection maps from these crystals were
      examined for two-fold symmetry via difference maps between the unsymmetrized
      averages and their 180 degrees rotation. A comparison of the final maps shows a
      high degree of two-fold symmetry, with only slight differences noted in the low
      density regions of the two halves of the structure. The interpretation is that PS
      II is a dimer, with the further suggestion that the two reaction center cores may
      have slightly different complements of antennae polypeptides.

PMID- 9630731
TI  - A calorimetric study of pH-dependent thermal unfolding of leghemoglobin a from
      soybean.
AB  - The purpose of the present work is to study the pH-dependent thermal denaturation
      of soybean leghemoglobin fraction a in a cyanide complex (Lba.CN) and to compare
      the results with those of myoglobin (Mb), apomyoglobin (apoMb) and
      cyanometmyoglobin (Mb.CN) as well. Comparing measured calorimetrically change of
      enthalpy (DeltaHcal) and calculated Van't Hoff change of enthalpy (DeltaHvh) we
      have found that heat denaturation of Lba.CN can be described by the two-state
      transition model. The average value of the change of heat capacity (DeltaCpd) of
      Lba.CN is between such values for apoMb and Mb.CN suggesting for some
      stabilisation role of the cyanide ion (CN-) on the protein molecule. The maximum
      change of Gibbs free energy (DeltaGmax) of Lba.CN is between 7.0 and 11.2
      kcal/mol depending on pH. The heat-denaturation of the protein occurs on heating
      the protein solution above 25 degrees C while the cold-denaturation occurs on
      cooling the protein below 25 degrees C.

PMID- 9630734
TI  - Medicare fraud: up close and personal.

PMID- 9630733
TI  - The pro-oxidant and antioxidant effects of vitamin C.

PMID- 9630735
TI  - Ascorbic acid in the prevention and treatment of cancer.
AB  - Proposed mechanisms of action for ascorbic acid (ascorbate, vitamin C) in the
      prevention and treatment of cancer include enhancement of the immune system,
      stimulation of collagen formation necessary for "walling off" tumors, inhibition
      of hyaluronidase which keeps the ground substance around the tumor intact and
      prevents metastasis, prevention of oncogenic viruses, correction of an ascorbate
      deficiency often seen in cancer patients, expedition of wound healing after
      cancer surgery, enhancement of the effect of certain chemotherapy drugs,
      reduction of the toxicity of other chemotherapeutic agents such as Adriamycin,
      prevention of free radical damage, and neutralization of carcinogenic substances.
      Scottish as well as Japanese studies have pointed to the potential benefit of
      high dose vitamin C for the treatment of "terminal" cancer. Mayo Clinic studies,
      however, have contradicted the Scottish and Japanese findings, resulting in
      accusations of methodological flaws from both sides. Numerous epidemiological
      studies have pointed to the importance of dietary and supplemental ascorbate in
      the prevention of various types of cancer including bladder, breast, cervical,
      colorectal, esophageal, lung, pancreatic, prostate, salivary gland, stomach,
      leukemia, and non-Hodgkin's lymphoma.

PMID- 9630736
TI  - The detoxification enzyme systems.
AB  - The human body is exposed to a wide array of xenobiotics in one s lifetime, from
      food components to environmental toxins to pharmaceuticals, and has developed
      complex enzymatic mechanisms to detoxify these substances. These mechanisms
      exhibit significant individual variability, and are affected by environment,
      lifestyle, and genetic influences. The scientific literature suggests an
      association between impaired detoxification and certain diseases, including
      cancer, Parkinson's disease, fibromyalgia, and chronic fatigue/immune dysfunction
      syndrome. Data regarding these hepatic detoxification enzyme systems and the body
      s mechanisms of regulating them suggests the ability to efficiently detoxify and
      remove xenobiotics can affect these and other chronic disease processes. This
      article reviews the myriad detoxification enzyme systems, their regulatory
      mechanisms, and the dietary, lifestyle, and genetic factors influencing their
      activities, as well as laboratory tests available to assess their functioning.

PMID- 9630738
TI  - Folates: supplemental forms and therapeutic applications.
AB  - Folates function as a single carbon donor in the synthesis of serine from
      glycine, in the synthesis of nucleotides form purine precursors, indirectly in
      the synthesis of transfer RNA, and as a methyl donor to create methylcobalamin,
      which is used in the re-methylation of homocysteine to methionine. Oral folates
      are generally available in two supplemental forms, folic and folinic acid.
      Administration of folinic acid bypasses the deconjugation and reduction steps
      required for folic acid. Folinic acid also appears to be a more metabolically
      active form of folate, capable of boosting levels of the coenzyme forms of the
      vitamin in circumstances where folic acid has little to no effect.
      Therapeutically, folic acid can reduce homocysteine levels and the occurrence of
      neural tube defects, might play a role in preventing cervical dysplasia and
      protecting against neoplasia in ulcerative colitis, appears to be a rational
      aspect of a nutritional protocol to treat vitiligo, and can increase the
      resistance of the gingiva to local irritants, leading to a reduction in
      inflammation. Reports also indicate that neuropsychiatric diseases secondary to
      folate deficiency might include dementia, schizophrenia-like syndromes, insomnia,
      irritability, forgetfulness, endogenous depression, organic psychosis, peripheral
      neuropathy, myelopathy, and restless legs syndrome.

PMID- 9630737
TI  - Dimercaptosuccinic acid (DMSA), a non-toxic, water-soluble treatment for heavy
      metal toxicity.
AB  - Heavy metals are, unfortunately, present in the air, water, and food supply.
      Cases of severe acute lead, mercury, arsenic, and cadmium poisoning are rare;
      however, when they do occur an effective, non-toxic treatment is essential. In
      addition, chronic, low-level exposure to lead in the soil and in residues of lead
      based paint, to mercury in the atmosphere, in dental amalgams and in seafood, and
      to cadmium and arsenic in the environment and in cigarette smoke is much more
      common than acute exposure. Meso-2,3-dimercaptosuccinic acid (DMSA) is a
      sulfhydryl-containing, water-soluble, non-toxic, orally-administered metal
      chelator which has been in use as an antidote to heavy metal toxicity since the
      1950s. More recent clinical use and research substantiates this compound s
      efficacy and safety, and establishes it as the premier metal chelation compound,
      based on oral dosing, urinary excretion, and its safety characteristics compared
      to other chelating substances.

PMID- 9630739
TI  - Inositol hexaniacinate.

PMID- 9630740
TI  - 5-hydroxytryptophan.

PMID- 9630741
TI  - Serenoa repens.

PMID- 9630742
TI  - Abdominal B (AbdB) Hoxa genes: regulation in adult uterus by estrogen and
      progesterone and repression in mullerian duct by the synthetic estrogen
      diethylstilbestrol (DES).
AB  - Mice deficient for the Abdominal B (AbdB) Hox gene Hoxa-10 exhibit reduced
      fertility due to defects in implantation. During the peri-implantation period
      Hoxa-10 is sequentially expressed in the uterine epithelium and stroma. These
      observations, combined with the stringent regulation of uterine implantation by
      ovarian steroids, prompted us to test whether estrogen and progesterone directly
      regulate the expression of Hoxa-10 and other AbdB Hoxa genes. Here we show that
      Hoxa-10 expression in the adult uterus is strongly activated by progesterone.
      This activation is blocked by the progesterone receptor antagonist RU486 and is
      independent of new protein synthesis. In addition, Hoxa-10 expression is
      repressed by estrogen in a protein synthesis-independent manner. Analysis of
      adjacent AbdB Hoxa genes reveals that Hoxa-9 and a-11 are also activated in a
      colinear fashion by progesterone but differentially regulated by estrogen. These
      results suggest that the regulation of AbdB Hox gene expression in the adult
      uterus by ovarian steroids is a property related to position within the cluster,
      mediated by the direct action of estrogen and progesterone receptors upon these
      genes. We next examined whether the embryonic expression of Hoxa10 is regulable
      by hormonal factors. Previous work has demonstrated that perinatal administration
      of the synthetic estrogen diethylstilbestrol (DES) to mice and humans produces
      uterine, cervical, and oviductal malformations. Certain of these phenotypes
      resemble those in Hoxa-10 knockout mice, suggesting that Hoxa-10 gene expression
      might be repressed by DES during reproductive tract morphogenesis. Exposure of
      the developing female reproductive tract to DES, either in vivo or in organ
      culture, represses the expression of Hoxa-10 in the Mullerian duct. Thus, these
      data not only establish a direct link between ovarian steroids and AbdB Hoxa gene
      expression in the adult uterus, but also provide a potential mechanism for the
      teratogenic effects of DES on the developing reproductive tract.

PMID- 9630743
TI  - Requirement for Brn-3b in early differentiation of postmitotic retinal ganglion
      cell precursors.
AB  - The Brn-3 subfamily of POU domain transcription factors consists of Brn-3a, -3b,
      and -3c, which are important regulators for sensorineural development. Despite
      the expression of all three factors in retinal ganglion cells, earlier studies
      have shown that Brn-3b is the only one among the three Brn-3 genes that is
      essential for development of approximately 70% of ganglion cells in the murine
      retina. I report here that Brn-3b displays a spatiotemporal expression pattern
      characteristic of the dynamic profile of ganglion cell genesis during murine
      retinal development. Moreover, it is initially turned on in postmitotic ganglion
      cell precursors 2 days before the onset of Brn-3a and -3c expression in
      differentiated ganglion cells. During the entire period of retinal ganglion cell
      genesis, the postmitotic ganglion cell precursors that would normally become Brn
      3b+ cells fail to properly differentiate in Brn-3b-/- mice, as evidenced by a
      twofold reduction in the optic nerve size and diminished expression of several
      ganglion cell markers. The undifferentiated ganglion cell precursors appear to be
      degenerated by apoptosis within the ganglion cell layer during the perinatal and
      early postnatal period. I propose that retinal ganglion cells develop following
      two separate differentiation pathways--Brn-3b dependent and Brn-3b independent.
      In the Brn-3b-dependent mechanism, Brn-3b may be required to initiate a
      particular differentiation program for a large set of postmitotic ganglion
      precursors to properly differentiate into the 70%, Brn-3b-dependent retinal
      ganglion cells.

PMID- 9630744
TI  - The role of morphogenetic cell death during Drosophila embryonic head
      development.
AB  - This article addresses the role of programmed cell death (apoptosis) during
      embryonic head development of Drosophila. Previous studies showed that reaper
      (rpr) is expressed in and required by cells undergoing apoptosis. We have
      analyzed the correlation between the pattern of expression of rpr and
      morphogenetic movements affecting head development. Furthermore, we have
      investigated the defects in head development resulting from the absence of
      apoptosis in embryos deficient for rpr. Our results show that, in the head,
      domains of high incidence of cell death as marked by expression of rpr correlate
      with regions where most morphogenetic movements occur; these regions are involved
      in formation of mouth structures, the internalization of neural progenitors, and
      head involution. Cellular events driving these movements are delamination,
      invagination, and intercalation as well as disruption and reformation of contacts
      among epithelial cells. The analysis of rpr-deficient embryos demonstrates that,
      despite of the widespread occurrence of apoptosis during normal head
      morphogenesis, many aspects of this process proceed in an apparently unperturbed
      manner even when cell death is blocked. In particular, movements that happen
      early during embryonic development and that are evolutionarily more ancient
      (e.g., formation of the dorsal ridge and the pharynx) take place almost normally
      in rpr-deficient embryos. Later events which are mostly associated with head
      involution (e.g., retraction of the clypeolabrum, formation of the dorsal pouch,
      fusion of lateral gnathal lobes) are evolutionarily more recent and fail to occur
      normally in rpr-deficient embryos.

PMID- 9630746
TI  - Additional vegetative growth in maize reflects expansion of fates in preexisting
      tissue, not additional divisions by apical initials.
AB  - The maize shoot is usually determinate: the apical meristem produces a fixed
      number of vegetative nodes before it switches to tassel development. Culturing
      maize meristems, however, delays their determinacy. Cultured meristems may form
      up to twice the usual number of vegetative nodes. Clonal analysis of the "extra"
      vegetative nodes reveals that these nodes are the product of conversion, roughly
      equivalent to a homoeotic transformation, of tissue that otherwise would form the
      base of the tassel. Altered activity of the apical initials does not generate the
      extra vegetative growth. The conserved, stereotypical activity of the apical
      initials even in the face of radically prolonged vegetative growth suggests that
      apical initials in this annual grass may acquire a highly restricted fate
      (presporogenous tissue) early in embryogenesis.

PMID- 9630745
TI  - Mutual regulation of decapentaplegic and hedgehog during the initiation of
      differentiation in the Drosophila retina.
AB  - Neuronal differentiation in the Drosophila retinal primordium, the eye imaginal
      disc, begins at the posterior tip of the disc and progresses anteriorly as a
      wave. The morphogenetic furrow (MF) marks the boundary between undifferentiated
      anterior cells and differentiating posterior cells. Anterior progression of
      differentiation is driven by Hedgehog, synthesized by cells located posterior to
      the MF. We report here that hedgehog (hh), which is expressed prior to the start
      of differentiation along the disc's posterior margin, also plays a crucial role
      in the initiation of differentiation. Using a temperature-sensitive allele we
      show that hh is normally required at the posterior margin to maintain the
      expression of decapentaplegic (dpp) and of the proneural gene atonal. In
      addition, we find that ectopic differentiation driven by ectopic dpp expression
      or loss of wingless function requires hh. Consistent with this is our observation
      that ectopic dpp induces the expression of hh along the anterior margin even in
      the absence of differentiation. Taken together, these data reveal a novel
      positive regulatory loop between dpp and hh that is essential for the initiation
      of differentiation in the eye disc.

PMID- 9630747
TI  - Endogenous and ectopic expression of noggin suggests a conserved mechanism for
      regulation of BMP function during limb and somite patterning.
AB  - The gene noggin, originally cloned in Xenopus, encodes a secreted factor
      expressed in the Spemann organizer, where it functions to oppose the ventralizing
      influence of bone morphogenetic proteins (BMPs). Noggin protein acts by binding
      directly to BMPs, thereby preventing them from interacting with their receptors.
      Here we describe the pattern of expression of the chicken noggin gene during
      somite and limb development, two tissues in which BMPs have been postulated to
      play essential patterning roles. We find that noggin is expressed in dynamic
      restricted patterns consistent with an important role in the modulation of BMP
      signaling. Using a replication competent retrovirus we have ectopically expressed
      noggin in developing somitic and limb bud mesoderm and observed phenotypes
      consistent with complete block of BMP activity. This includes suppression of
      lateral somite differentiation and, in the limb, complete inhibition of
      chondrogenesis and local suppression of programmed cell death. In addition, we
      find that ectopic noggin expression in the limb has no effect on anteroposterior
      limb pattern, suggesting that BMPs are unlikely to play a significant role in
      this process. Taken together,, our results indicate that noggin is a key
      regulator of vertebrate limb and somite patterning and suggest that the
      antagonistic Noggin-BMP interaction is a widely used mechanism to modulate BMP
      signaling during multiple inductive events in vertebrate embryogenesis.

PMID- 9630748
TI  - Overexpression of zeste white 3 blocks wingless signaling in the Drosophila
      embryonic midgut.
AB  - The extracellular signals encoded by the Wnt family of genes regulate growth and
      differentiation in several developmental processes in both vertebrates and
      invertebrates. Genetic studies of the signaling pathway of the Drosophila Wnt
      homologue, Wingless, have identified a number of genes, including zeste white 3,
      which function to transduce the Wingless signal. zeste white 3 encodes a
      serine/threonine kinase. We have previously proposed that the Wingless signal is
      mediated by repression of this kinase activity [E. Siegfried, E.L. Wilder, and N.
      Perrimon (1994) Nature 367, 76-80]. Here we have tested this hypothesis by
      overexpressing zeste white 3 in a tissue-specific fashion using the UAS/GAL4
      binary expression system. We demonstrate that elevated levels of zeste white 3 in
      the ectoderm and mesoderm result in phenotypes that resemble a loss of wingless.
      Overexpression of zeste white 3 in the mesoderm disrupts several Wingless
      dependent processes including the specification of a unique cell type in the
      larval midgut, the formation of the second midgut constriction, and the
      expression of Wingless target genes Ultrabithorax and decapentaplegic in the
      mesoderm and labial in the endoderm. Zeste white 3 regulates the stability of
      Armadillo which is essential for transducing the Wingless signal to the nucleus.
      We show that zeste white 3 overexpression blocks Wingless signaling through the
      modulation of Armadillo since expression of a constitutively active form of
      Armadillo, which is independent of Zeste white 3 regulation, is epistatic to
      overexpression of zeste white 3.

PMID- 9630749
TI  - Muscle-specific cell ablation conditional upon Cre-mediated DNA recombination in
      transgenic mice leads to massive spinal and cranial motoneuron loss.
AB  - We describe here a binary transgenic system based on Cre-mediated DNA
      recombination for genetic cell ablation in mice that enabled us to obtain
      skeletal muscle-deficient embryos by mating two phenotypically normal transgenic
      lines. In those embryos, skeletal muscles are eliminated as a consequence of the
      expression of the gene encoding the diphtheria toxin A fragment. Cell ablation
      occurs gradually beginning approximately on embryonic day (E) 12.5, and by E18-5
      almost all skeletal muscle is absent. Analysis of the consequences of muscle cell
      ablation revealed that almost all spinal motoneurons are lost by E18.5, providing
      strong evidence that survival of spinal motoneurons during embryogenesis is
      dependent on signals from their target tissue, skeletal muscle, and that trophic
      signals produced by nonmuscle sources are sufficient to support survival of no
      more than 10% of embryonic spinal motoneurons in the absence of muscle-derived
      signals. There was also substantial loss of cranial (hypoglossal and facial)
      motoneurons in the muscle-deficient embryos, thus indicating that cranial
      motoneuron survival is also dependent on trophic signals produced by their target
      tissue. Although spinal motoneurons are a major target of spinal interneurons,
      the loss of motoneurons did not affect interneuron survival. Muscle-deficient
      embryos had a cleft palate and abnormalities of the lower jaw, raising the
      possibility that they might serve as a mouse model for the human disorder, Robin
      sequence. The data reported here demonstrate the utility of a binary transgenic
      system for obtaining mouse embryos in which a specific cell population has been
      ablated, so that its role in embryonic development can be studied.

PMID- 9630750
TI  - The cloche and spadetail genes differentially affect hematopoiesis and
      vasculogenesis.
AB  - In vertebrates, hematopoietic and vascular progenitors develop from ventral
      mesoderm. The first primitive wave of hematopoiesis yields embryonic red blood
      cells, whereas progenitor cells of subsequent definitive waves form all
      hematopoietic cell lineages. In this report we examine the development of
      hematopoietic and vasculogenic cells in normal zebrafish and characterize defects
      in cloche and spadetail mutant embryos. The zebrafish homologs of lmo2, c-myb,
      fli1, flk1, and flt4 have been cloned and characterized in this study. Expression
      of these genes identifies embryonic regions that contain hematopoietic and
      vascular progenitor cells. The expression of c-myb also identifies definitive
      hematopoietic cells in the ventral wall of the dorsal aorta. Analysis of b316
      mutant embryos that carry a deletion of the c-myb gene demonstrates that c-myb is
      not required for primitive erythropoiesis in zebrafish even though it is
      expressed in these cells. Both cloche and spadetail mutant embryos have defects
      in primitive hematopoiesis and definitive hematopoiesis. The cloche mutants also
      have significant decreases in vascular gene expression, whereas spadetail mutants
      expressed normal levels of these genes. These studies demonstrate that the
      molecular mechanisms that regulate hematopoiesis and vasculogenesis have been
      conserved throughout vertebrate evolution and the clo and spt genes are key
      regulators of these programs.

PMID- 9630751
TI  - The paternal effect gene ms(3)sneaky is required for sperm activation and the
      initiation of embryogenesis in Drosophila melanogaster.
AB  - Although a large number of maternal factors are known to be essential for
      fertilization or the earliest stages of embryogenesis in Drosophila melanogaster,
      the role of paternally supplied products is not clearly understood. Paternal
      effect mutations provide a means to identify factors specifically required by the
      sperm after its entry into the egg. Here we describe the third strict paternal
      effect gene to be identified in Drosophila ms(3)sneaky(snky), which defines the
      earliest developmental arrest phenotype so far described. Characterization of two
      independently isolated snky mutations showed that they affected male fertility,
      but not viability or female fertility. Cytological analyses showed that
      spermatogenesis proceeded normally in snky males. However, the snky defect was
      evident after sperm entry into the egg; snky sperm did not undergo nuclear
      decondensation, form a functional male pronucleus, or initiate mitotic divisions
      in the egg. Immunolocalization of tubulin and Drosophila Centrosomin, a known
      centrosomal component, showed that snky-inseminated eggs failed to reconstitute a
      microtubule-organizing center. In addition, snky sperm chromatin retained the
      histochemical properties of mature sperm chromatin for several hours after sperm
      entry, showed reduced staining with membrane-impermeant nuclear dyes, and failed
      to replicate. We conclude that the snky+ product is required for the initial
      response of the sperm to cytoplasmic cues in the egg and for the subsequent
      initiation of embryogenesis in Drosophila. We suggest that all of the snky
      defects can be explained by the failure of the sperm plasma membrane to break
      down after entry into the egg.

PMID- 9630752
TI  - Specification of the hindbrain fate in the zebrafish.
AB  - We determine the timing of neural commitment by hindbrain tissue in the zebrafish
      using microsurgical transplantation. When transplanted at shield stage to the
      ventral side of the embryo, presumptive hindbrain cells are not committed, as
      they can adapt to their environment and give rise to epidermis. In contrast, when
      transplanted at 80% epiboly, hindbrain cells retain their neural fate and express
      neural-specific antigens. Moreover, they are able to maintain regional fate, as
      is evident by the expression of the hindbrain-specific marker, Krox20. In
      addition, we observe that committed hindbrain tissues are able to induce
      presumptive ventral epidermis to form neural crest derivatives, otic vesicles,
      and neural tissues. We propose that hindbrain progenitors have acquired regional
      identity as a group at 80% epiboly even before making vertical contact with axial
      mesoderm. These results suggest that planar induction may constitute a
      significant component in the zebrafish neural patterning pathway.

PMID- 9630753
TI  - Obesity.

PMID- 9630754
TI  - Carcinoid to cecal bowel localization: a case report and literature review.
AB  - The authors report a case of cecal malignant carcinoid, diagnosticated in a 68
      years old male patient. Carcinoid tumours are rare neoplasm and their behaviour
      seems to change with the localization. Cecal carcinoid represents only 2-3% of
      gastrointestinal carcinoid. Some times it is discovered incidentally at autopsy,
      surgery or endoscopy. The aim of this paper has been to review, in literature,
      the frequency, treatment and prognosis of this neoplasm.

PMID- 9630755
TI  - Biofragmentable anastomosis ring (BAR) in intestinal surgery: review of 21 cases
      and evaluation of postoperative morbidity.
AB  - The authors report their experience with the use of biofragmentable anastomosis
      ring in intestinal anastomosis: 21 patients underwent intestinal resection and
      anastomosis by BAR. There was no operative mortality. One patient developed an
      anastomotic leak and three patients had symptoms of intestinal obstruction. The
      endoscopic follow up showed no late complications. Technical factors regarding
      the BAR are discussed. Advantages appear to be a safe, rapid and easy alternative
      to hand and stapled intraperitoneal large bowel anastomosis.

PMID- 9630756
TI  - Home pharmacological therapy in an ultra-75 years old population in Troina (inner
      Sicily).
AB  - In a group of 365 subjects, 75 years old and ultra, living in Troina (Sicily), a
      study on prevalence of dementia has been carried out. In the questionnaire, used
      to collect information about subjects' health, one of the questions concerned the
      assumption of drugs. The interviewer transcribed the name of the drugs and then
      coded the related chemical-pharmacological classification, according to the 14
      principal groups of the guide of the National Health Service. Up to 9 drugs, on a
      daily basis, were registered. The total amount of prescriptions was 889, equal to
      2.4 per person, with a clear prevalence of the females. 26.1% of the sample did
      not take any drug. The mode of assumptions was 3 a day. The cardiovascular system
      is at the top of prescriptions, with 39% of the total, followed by the
      gastroenteric apparatus and metabolism (17.9%), the nervous system (16.7%), the
      haemopoietic system (8.4%), the musculo-skeletal system (6.2%), the respiratory
      apparatus (5.7%), and so on the others. For each principal group of drugs, those
      more represented are identified, obtaining other information about the
      practitioners' choices. Among the principal subgroups of cardiovascular system,
      it is worth mentioning anti-hypertensives, diuretics and antianginal, each of
      them with their own subgroups. In the gastroenteric apparatus and metabolism
      group, the latter comprises the drugs for the treatment of diabetes: oral
      hypoglicaemics and insulin. These drugs allow to identify 34 cases of diabetes:
      29 NIDD and 5 IDD. Analogous evaluations for drugs of other groups and
      comparisons with a few data available in literature are carried out. Surveying
      the drugs used in a population is useful: (i) to evaluate the health state; (ii)
      to identify the dominant disease; (iii) to draw comparisons with other
      populations; (iiii) to follow the evolution of pharmacotherapy.

PMID- 9630757
TI  - A new classification of varicose veins to compare various surgical strategies.
AB  - Considering the presupposition that chronic venous insufficiency (CVI) and
      varicose veins classifications are extremely difficult, and that none of those
      presently in use are sufficiently complete, the authors propose the
      classification of the haemodynamic venous disease (HVD) and of the varicose veins
      from the clinical, anatomotopographical, etiopathogenetical and haemodynamical
      point-of-view. This type of classification allows us to closely follow the
      disease's evolution, to distinguish the benign forms from the more aggressive
      ones, and to evaluate the results of the medical, surgical and schlerotherapical
      treatments, from the efficiently, functional, instrumental and aesthetically
      point-of-view.

PMID- 9630758
TI  - Variation of acid-base balance, glycemia, electrolytes and ETCO2 after fast i.v.
      infusion of 5% fructose and/or glucose.
AB  - Intraoperative fluid infusion has precise goals and the rapid infusion of some
      solutions can induce important modifications of homeostatic parameters, which
      must be known. Rapid infusion of fructose and glucose 5% solutions has been
      carried out and modifications of acid-base balance, glycemia, serum electrolytes,
      ETCO2 have been registered. The administration of fructose 5% determines a mixed
      acidosis while the administration of glucose does not cause this phenomenon; the
      administration of both carbohydrates reduces serum chloride and sodium, while
      serum potassium rises only after fructose infusion and glycemia only after
      glucose infusion. All the variations described reach significant levels.

PMID- 9630759
TI  - Feedback inhibition of insulin secretion and insulin resistance in polycystic
      ovarian syndrome with and without obesity.
AB  - Hyperinsulinemia/insulin resistance is a well-known feature of polycystic ovarian
      (PCO) syndrome. In this study, the comparative roles of the peripheral tissues
      and the pancreatic beta-cells in its pathogenesis were evaluated. We determined
      basal serum C-peptide values (index of insulin secretion) and in vivo insulin
      action on peripheral glucose utilization (by the euglycemic hyperinsulinemic
      clamp technique) in obese (n = 5) and nonobese (n = 5) PCO women compared to
      obese (n = 5) and nonobese (n = 5) normal ovulatory women. During the clamp, feed
      back inhibition of insulin on insulin secretion was studied by C-peptide
      percentage suppression. Serum C-peptide basal values did not differ significantly
      between the four groups. Insulin stimulated glucose utilization, expressed as M
      value, was significantly decreased in both PCO groups compared to normal
      ovulatory women (p < 0.005). The metabolic clearance rate of glucose (MCR) and
      insulin (M/I) had the same behaviour. No differences were found between M, MCR
      and M/I values and the two groups of PCO subjects (obese/nonobese). The C-peptide
      percentage suppression was similar in all the groups. We conclude that PCO women
      have a significant insulin resistance that is independent of obesity, while basal
      and insulin-inhibited insulin secretion do not differ from normal-cycle subjects.

PMID- 9630760
TI  - On a case of "Macrodystrophia lipomatosa".
AB  - Macrodistrophia Lipomatosa is a congenital malformation of rare finding and
      unknown pathogenic mechanism. The pathology is mainly characterized by the
      interest of lower extremities and peculiar macroscopic feature is the presence of
      hyperthrophic fibro-adipose tissue. In our experience the localization to the
      upper extremities and the presence of uncommon clinical signs show the importance
      of instrumental investigation: MRI and CT for an accurate examination and to
      exclude other types of localized gygantism.

PMID- 9630761
TI  - Genetico-mathematical analysis of the inheritance pattern of ulcer disease. A
      posteriori methods. The maximum likelihood method.
AB  - Inheritance pattern of ulcer disease was analysed genetico-mathematically using
      one of the a posteriori methods--the method of maximum likelihood. We studied the
      families of 351 hereditary predisposed probands of whom 57 with type II gastric
      ulcer disease, 27 with type III gastric ulcer disease and 267 with duodenal ulcer
      disease. The types of ulcer disease were determined according to H. Johnson. The
      analysis of the patients with duodenal ulcer also included the types of familial
      predisposition of the probands. The results yielded by the maximum likelihood
      method excluded to a great degree the possibility of monogenic transmission of
      ulcer disease. None to the three types of peptic ulcer showed autosomal recessive
      pattern of inheritance; it was not found even in the families with phenotypically
      healthy but hereditary predisposed parents. No evidence was found of autosomal
      dominant pattern of inheritance of the disease in all studied groups including
      the families with one sick parent. This is supported by the different values of
      the segregation coefficients in the families with one sick father and one sick
      mother. The absence of evidence for monogenic mode of inheritance of the disease
      indicated by the detailed genetico-mathematical analysis should be further
      evaluated by the criteria of polygenicity.

PMID- 9630762
TI  - A novel ETA-AAS background reduction method for determination of lead and cadmium
      in urine.
AB  - Urinary lead and cadmium level were determined in double diluted urine samples
      using two modifiers: 1% HNO3 (own modification) and 1.6% NH4H2PO4 that is
      generally used for matrix modification. The background signal is reduced in the
      samples diluted with 1% HNO3 because of the modifying effect of nitric acid.
      Lower variation coefficients were obtained in a run of 10 determinations of each
      of the samples processed by our method which is an advantageous feature compared
      with the method using 1.6% NH4H2PO4 as a modifier. Recovery is between 95 and
      105% for both methods. The analytical performance, flexible pre-instrumental
      preparation and minimized risk of sample contamination make the use of 1% HNO3
      modifier a reliable method in the routine practice of determination of the
      urinary Pb and Cd level.

PMID- 9630763
TI  - Dimensions of hard dental tissues and pulp cavity of the crown in first
      mandibular molar measured with computerized tomography.
AB  - In spite of the numerous studies (carried out by different authors and with
      various methods) to determine the dimensions of teeth, the size of the enamel and
      the dentin in different topographic regions of the tooth crown have not yet been
      established. The present study aimed at developing a mathematical model of the
      first mandibular molar by measuring the thickness of its enamel, dentin and pulp
      cavity. The study was conducted upon 15 first mandibular molars in 18-year-old
      high-school students with intact dentition using computerized tomography (SY
      3000). The hard dental tissues dimensions in different topographic regions of
      first mandibular molar were determined by densoprofile measuring of four 1-mm
      wide sections oriented in relation to the frontal plane and axis of the tooth.
      The obtained data are presented in a tabular form. The basic values for the crown
      height, the mediodistal and vestibulo-oral dimensions do not differ significantly
      from the values that are currently widely-known in the literature. The thickness
      of the enamel and dentin in different topographic regions are determined in
      details, which gives a clear picture of the safety zones location around the pulp
      cavity. On the basis of the obtained results it is possible to develop a
      mathematical model of the first mandibular molar.

PMID- 9630764
TI  - Topographic distribution of occlusal contacts of the first mandibular molar-
      comparative study.
AB  - The specification of the occlusal contacts in the posterior teeth region is a
      necessary clinical reference point for creating optimal interrelations between
      the teeth and dentition. The methods, such as the photo-occlusal method, the
      quasiplanimetric method, two-phase proof imprint in central occlusion, recording
      of contacts with profile wax, that have been used in studying the number and
      location of occlusal contacts at various positions of the mandible in relation to
      the maxilla are exact but difficult to apply clinically. The purpose of the
      present study is to find the topographic distribution of occlusal contacts in
      intact first mandibular molars using a method that is easy to utilise clinically
      and to compare the present results with the findings of the authors. The
      masticatory teeth of 100 high-school students (18 years old) without subjective
      complaints or objective structural or functional disorders of the
      temporomandibular joint were studied by means of articulation paper. From that
      sample 41 students with intact dentition and orthognathic occlusion were
      selected. The first mandibular molars (N = 77) were studied. The results are as
      follows. The occlusal contacts in the first mandibular molar vary from 1 to 7.
      The greatest percentage of contacts is observed in the tubercles. In the first
      mandibular molar the biting pressure upon the tubercle apex areas is greater
      compared to that on the sloping areas. Our results were compared with the
      findings obtained by the other three methods mentioned above. Our method allows
      objective specification of the topographic distribution of occlusal contacts.

PMID- 9630765
TI  - A case of primary Sjogren's syndrome in combination with chronic
      mesangiocapillary glomerulonephritis and interstitial nephritis.
AB  - The authors present an extremely rare case of combination of primary Sjogren's
      syndrome and chronic glomerulonephritis, which was subsequently found to be
      mesangiocapillary on pathohistologic examination. METHODS: This case of
      mesangiocapillary glomerulonephritis in combination with interstitial nephritis
      is characterized in terms of the clinical, laboratory, immunologic and
      instrumental methods for diagnosis. Percutaneous kidney biopsy was performed and
      the characteristic findings on light microscopy were recorded. RESULTS: The
      therapeutic regimen consisting of pulse therapy with Immunovenin-intact and
      cyclophosphamide resulted in long-term clinical and laboratory remisson of the
      glomerulopathy and positively influenced the remaining syndromes. CONCLUSION:
      Pulse therapy with these drugs is an alternative to conventional pathogenetic
      therapy; it can also be the therapeutic modality of choice in cases similar to
      the one described here having in mind the long-term therapeutic remission.

PMID- 9630766
TI  - Clinical manifestations and diagnosis of bacterial vaginosis in a clinic of
      sexually transmitted diseases.
AB  - BACKGROUND: The aim of the present study was to evaluate the prevalence of
      bacterial vaginosis (BV) and correlate it with the data from the patient history
      and clinical manifestations in women attending an STD clinic and to compare two
      methods of diagnosis. MATERIAL AND METHODS: On hundred and fifty-six women, aged
      15 to 45, attending the STD clinic of the Higher Medical Institute in Plovdiv,
      Bulgaria were enrolled in the study. All women were evaluated for the presence of
      BV using standard criteria and Gram stain of vaginal secretions. Symptoms,
      clinical manifestations, methods of contraception and sexual life and smoking
      were analyzed. RESULTS: Using clinical criteria and Gram's stain, BV was
      diagnosed in 59 women (37.8%). BV was associated with age younger than 25 years,
      risk sexual behaviour, e.g. lack of a permanent sexual partner during the
      preceding 6 months, use of an intrauterine device, other STDs and smoking.
      Symptoms are not a reliable way of diagnosing BV, but the presence of a
      homogeneous vaginal discharge on examination, a positive amine test and pH > or =
      4.7 are common in BV. A negative correlation was found between the number of
      lactobacilli and BV. CONCLUSIONS: BV is common in women attending STD clinic and
      is associated with other STDs, e.g. infection with Neisseria gonorrhoeae,
      Chlamydia trachomatis, Trichomonas vaginalis, human papilloma virus. The Gram
      stain method is inexpensive and easy to perform for the laboratory diagnosis of
      BV; it can be used reliably as an indicator of the changes preceding BV.

PMID- 9630767
TI  - Effect of pectin on some electrolytes and trace elements in patients with
      hyperlipoproteinemia.
AB  - BACKGROUND: Water-soluble dietary fibres are widely used in preventive and
      curative nutrition, especially in cases of hyperlipoproteinemia. Occurrence of
      disturbances of the electrolyte and trace element metabolism causing adverse
      effects in long-term treatment with pectin can be theoretically substantiated.
      METHODS: Seventy three patients with hyperlipoproteinemia, aged from 40 to 69
      years, were included in the study. They were treated with a natural product,
      based on high-esterified pectin granulated with sorbitol. The patients were
      examined prior to the treatment and once monthly during the three-month course of
      therapy. RESULTS: The results of the comparative assessment of the electrolytes
      (sodium, potassium, chloride, ionised calcium, total and ionised magnesium)
      failed to reach statistical significance during the administration of the pectin
      product. Neither did the serum level of trace elements (iron and copper) change
      significantly during the observed period. CONCLUSIONS: The biochemical analysis
      of the serum level of certain electrolytes and trace elements indicate that daily
      administration of 15 g of high-esterified apple pectin for a three-month period
      has no adverse effects. Therefore pectin products can be included in the
      therapeutic schedule in the treatment of hyperlipoproteinemia.

PMID- 9630768
TI  - Serum level of interferon alpha in patients with acute viral hepatitis B.
AB  - The serum level of interferon alpha (INF alpha) in patients with different
      clinical forms of acute viral hepatitis during the first 10 days, from day 11 to
      day 20, and after day 20 of the onset of jaundice was studied using the
      radioimmunoassay test of ABBOTT (ABBOTT-RIA). The patients were tested for
      presence of HBsAG and anti-HBs three months after the disease was over. 79.16% of
      the patient were found to have an elevated serum level of INF alpha during the
      first ten days of the onset of jaundice, this percentage decreasing in the days
      after that. The mean INF alpha levels were higher in the severer clinical forms
      of disease but the differences were not statistically significant. The highest
      INF alpha levels were found in acute hepatic insufficiency. The patients who
      tested negative for HBsAg three months after being discharged from hospital had
      significantly higher mean levels of INF alpha during the first 10 days of the
      onset of jaundice in comparison with the other carriers of this antigen.

PMID- 9630769
TI  - Traumatic intracerebral hematomas--diagnostic and therapeutic problem.
AB  - A retrospective analysis was performed of 79 patients with hematomas treated
      surgically or conservatively. The surgical modality was most often opted for in
      the following cases: patients with hematomas exceeding 4 cm in diameter; patients
      with hematomas causing a pronounced dislocation of cerebral structures; patients
      with multiple hematomas that can be accessed through a bone flap. Hematomas
      smaller than 4 cm in diameter as well as those located in several brain regions
      were found to tend easily to resorption at the control computer tomography due to
      which we preferred treating them using conservative therapeutic methods. This
      therapeutic approach to the patients with hematomas is supported by the
      statistical analysis. Comparison of the groups of survivors and nonsurvivors
      shows that the former predominated in cases of hematomas located in the frontal
      lobe; the latter are predominant when the hematomas are located in the temporal
      lobe of the brain. There was no difference between the groups of surgically and
      conservatively treated patients with respect to the outcome of the disease if it
      is improvement or death. In the group of patients who underwent conservative
      treatment there was a predominance of those patients that showed no improvement
      of the initial state. The following conclusions can be made: 1. Surgical
      treatment is most often administered to patients with hematomas greater than 4 cm
      in diameter and hematomas causing dislocation of the cerebral structures. 2. The
      patients at highest risk for adverse outcome are those with temporal location of
      the hematoma.

PMID- 9630770
TI  - Congenital chloride diarrhoea (presentation of two cases).
AB  - Two cases of congenital chloride diarrhoea in newborn infants are presented. The
      diagnosis was made by a combination of clinical findings--hydramnios, low birth
      weight, large abdomen, severe dehydration, dyselectrolytemia with hypochloremia
      and hypokalemia, and metabolic alkalosis. A crucial finding for the confirmation
      of the diagnosis was the fourfold rise of faecal CI exceeding the sum of sodium
      and potassium concentrations.

PMID- 9630771
TI  - A panel of indices for evaluation and performance of artificial ventilation and
      objective evaluation of the condition of low birth weight infants as compared
      with infants weighing more than 2500 grams.
AB  - BACKGROUND: Mechanical ventilation is an invasive life-supporting technique which
      profoundly affects different organs and systems of the newborn. Initiation and
      subsequent application of any respiratory or oxygenation strategy in the setting
      of the neonatal intensive care unit (ICU) requires sound knowledge and full
      comprehension of the underlying physiological and pathophysiological processes.
      MATERIAL AND METHODS: Fifty-nine low birth weight infants (LBW)--19 survivors
      (LBWS) and 40 nonsurvivors (LBWN)--who had received conventional mechanical
      ventilation during the neonatal period were followed over the time allowing data
      to reach statistical significance. We compared the results with those in newborns
      with birth weight greater than 2500 grams (results from a previous study) and
      found that the values, pattern of change and relationship between the different
      groups showed some interesting characteristics. The comparison of our results
      yields additional information with important predictive value. We made the
      following CONCLUSIONS: 1. There is a clear-cut difference in the pattern of
      change of indices between newborns with different birth weight. 2. There are a
      number of differences in the pattern of change of indices between the survived
      and non-survived which are independent of the birthweight. 3. The values and
      pattern of change of indices allows an evaluation of the degree of pulmonary
      dysfunction and the impairment of gas exchange and oxygenation. 4. The monitoring
      of the proposed panel of indices contributes towards the optimal application of
      the ventilation/oxygenation equipment. 5. The pattern of change of indices used
      is a source of timely and reliable information regarding the early and late
      prognosis in neonates receiving artificial ventilation.

PMID- 9630772
TI  - A case of large posterior mediastinal cystadenomatous goiter.
AB  - The authors present a case of large posterior mediastinal cystadenomatous goiter
      in an elderly man. The resection performed utilised a combined cervical and
      thoracic approach. The diagnostic and operative handicaps in deep and fixed
      mediastinal goiters are discussed.

PMID- 9630773
TI  - Effect of antiepileptic drugs on the thyroid gland in children with epilepsy
      (preliminary report).
AB  - Description of the side effects of antiepileptic drugs is commonly encountered in
      paediatric practice. In view of this we investigated the structural and
      functional changes undergone by the thyroid glands of epileptic children during
      the course of a long-term antiepileptic treatment. The study included 22 children
      with epilepsy aged 3.5 to 15 years. The thyroid status was assessed using
      clinical, ultrasound, and radioimmunological examinations. Clinical signs of
      initial hyperplasia of the thyroid gland were observed in 3 children. Volume
      abnormalities of the thyroid gland were found in 4 (18.2%) of the children.
      Abnormalities in the thyroid hormones and thyrotropin serum concentration were
      found in 5 children. The ultrasound examination revealed slight structural
      changes, decreased colloid uptake, and strip-like sprouts in 63.6% of the cases.
      These changes were significantly more common in children undergoing
      anticonvulsant polytherapy (12 of 22 children). The most general mechanisms of
      influence of the antiepileptic drugs on the thyroid status are discussed.

PMID- 9630774
TI  - Thalassemia intermedia in an infant.
AB  - We present a case of a two year old infant with jaundice in the neonatal period,
      anemia and splenohepatomegaly. Hemoglobin electrophoresis of the child and
      siblings revealed double heterozygosity of Lepore/beta thalassemia in the child
      and father, and heterozygous beta-thalassemia in the uncle. Structural variants
      giving rise to thalassemia phenotype are discussed.

PMID- 9630775
TI  - [Violence against the elderly. An almost daily occurrence].

PMID- 9630776
TI  - [Ischemic cerebral infarct in young adults. An overview of epidemiology,
      etiology, diagnosis and prognosis].
AB  - Some 5 to 10% of all ischemic insults occur in young adults and constitute a
      diagnostic-therapeutic challenge. The leading causes are atherosclerotic disease,
      vascular dissections, vasculitis and, in particular, cardioembolic events. In
      addition, there exists a broad spectrum of relatively rare disorders most of
      which need to be dealt within specialized neurological stroke units.
      Nevertheless, the etiology of up to 20% of such events remains unexplained. The
      present article provides an up-to-date review of the necessary etiological
      considerations, diagnostic measures, and results relevant to the prognosis of
      juvenile ischemic stroke.

PMID- 9630777
TI  - [Rehabilitation after stroke: aids for management and adjustment. Interview by
      Dr. med. vet. Susanne Kammerer].

PMID- 9630778
TI  - [Resources and needs in rehabilitation. Health care reality exemplified by the
      stroke patient].

PMID- 9630780
TI  - [The way to rational phytotherapy--a trip with impediments].

PMID- 9630779
TI  - [Symptomatic local therapy of the uncomplicated common cold. Multicenter
      controlled study of the effectiveness of an antiseptic lozenge].

PMID- 9630782
TI  - [Interview with Prof. Eser on morals and ethics in medicine. "The patient must
      not become an object of health measures." Ethics series in medicine, 1: Ethical
      codices. Interview by Elisabeth B. Moosmann].

PMID- 9630781
TI  - [Information system provides decision aids for the physician. Drugs in pregnancy
      and lactation].

PMID- 9630783
TI  - [The Human Genome Project--much more than basic research].

PMID- 9630784
TI  - [Preferences in general practice. Interview by Christine Vetter].

PMID- 9630785
TI  - [As physician in a town near the Polish border].

PMID- 9630786
TI  - Dosing of oral sumatriptan: a review of our first 104 patients.
AB  - BACKGROUND: The introduction of oral sumatriptan in the United States at doses of
      25 and 50 mg, compared with 100-mg tablets worldwide, has created the need to
      develop a protocol for appropriate dosing. METHODS: We evaluated the first 104
      patients in our practice to treat two migraine attacks with oral sumatriptan. For
      their first treatment with oral sumatriptan, patients were evaluated on their
      response to 25-mg tablets and the total number of tablets taken. For their second
      treatment, patients were evaluated on their response to sumatriptan, number of 25
      mg tablets taken, and dosage prescribed for future migraines. RESULTS: [table see
      text] After the second treatment, 41 patients (40%) continued therapy with 25-mg
      tablets, 54 (53%) were prescribed 50-mg tablets, 2 patients (2%) were prescribed
      two 50-mg tablets, and 5 patients (5%) were prescribed injectable sumatriptan.
      Seventy patients had previously used injectable sumatriptan, while 34 had not
      previously used sumatriptan. There were no significant differences in their
      response to oral sumatriptan. CONCLUSION: Oral sumatriptan was effective in
      clinical practice at doses of 25 and 50 mg. The majority of patients required
      more than one 25-mg tablet for a migraine attack, reflecting both inadequacy of
      dosing for some migraines and recurrence of headache, yet 40% of patients
      continued on treatment with 25-mg tablets. There were no significant differences
      in response to therapy in patients being switched from injectable to oral
      sumatriptan compared with those initiating therapy with oral sumatriptan. Both
      tablet strengths of oral sumatriptan are useful in clinical practice.

PMID- 9630787
TI  - Catecholaminergic innervation of the human dura mater involved in headache.
AB  - The catecholaminergic innervation of cranial dura mater in humans was studied by
      examining several dural zones (vascular, perivascular, intervascular) in
      different regions (basal, calvarial, occipital, frontal, tentorial, parietal,
      temporal). The results demonstrate that catecholaminergic nerve fibers are
      present in human cranial dura mater and that these fibers, after exposure to
      formaldehyde vapors, show the specific fluorescence of catecholamines. There are
      more dural catecholaminergic nerve fibers in the basal region than in the
      calvarial region. Moreover, these nerve fibers are more abundant in the
      perivascular dural zone than in the intervascular zone. We hypothesize that these
      catecholaminergic nerve fibers may be involved in headache.

PMID- 9630788
TI  - Epidemiologic and clinical characteristics of migraine and tension-type headache
      in Korea.
AB  - This is the first population-based epidemiologic study of chronic headache in
      South Korea. The diagnosis and classification of headache was according to the
      criteria of the International Headache Society. Sixty-eight percent of the
      studied population experienced headache during the preceding year. The estimated
      prevalences were 22.3% for migraine (male 20.2%, female 24.3%) and 16.2% for
      tension-type headache (male 17.8%, female 14.7%). In migraine, the 15- to 19-year
      age group showed maximal prevalence in both sexes (male 28.5%, female 34.7%). The
      prevalence of tension-type headache was highest in the 50- to 59-year age group
      in men (24.2%) and in the 20- to 29-year age group in women (20.2%). In migraine,
      headache intensity was more severe in women than in men, but in tension-type
      headache there was no difference in the severity of headache between the sexes.
      Phonophobia was the most common associated symptom of migraine (65.1%). In the
      migraine with aura group, the most common aura was visual disturbance, including
      scintillation and image distortion (82.3%). Only 24.4% of migraineurs and 12.3%
      of patients with tension-type headache had ever consulted a doctor for headache.
      The prevalence of migraine was not lower than in western countries and much
      higher than in previous studies conducted in other Asian countries.

PMID- 9630789
TI  - Headache and facial pain responsive to botulinum toxin: an unusual presentation
      of blepharospasm.
AB  - The diagnosis of blepharospasm is rarely considered in patients complaining of
      face pain or headache. This patient illustrates the importance of looking for
      blepharospasm in patients who present with headache or face pain, as her pain and
      blepharospasm were successfully treated with botulinum toxin type A injections.

PMID- 9630790
TI  - SUNCT syndrome. Two cases in Argentina.
AB  - Two patients suffering from SUNCT syndrome are presented. Some features are
      remarkable. The first patient was a 69-year-old man whose first crisis was
      located in the right supraorbital region. After a 4-month spontaneous remission,
      the pain returned to the upper part of the cheek, radiating to the supraciliary
      region on the same side, with lacrimation and conjunctival injection. Rhinorrhea
      was absent. The painful attacks were triggered by head movements. Clinical
      improvement occurred with carbamazepine treatment. The second patient was a 48
      year-old woman whose painful attacks lasted from 30 to 45 seconds followed by a
      burning sensation lasting 2 hours. Autonomic signs such as conjunctival
      injection, lacrimation, and edema and ipsilateral ptosis of the upper lid were
      rather marked. There was never any rhinorrhea. Her attacks were triggered by head
      and eye movements. She responded to the administration of corticosteroids and
      carbamazepine. According to these features, the two patients had SUNCT syndrome,
      and the positive carbamazepine response suggests a relationship with trigeminal
      neuralgia.

PMID- 9630791
TI  - [Antibiotics against myocardial infarction? The risk of resistance development
      must be considered].

PMID- 9630792
TI  - [When is the diagnosis of celiac disease correct? New guidelines for
      standardization of criteria].

PMID- 9630793
TI  - [Time waits for no one (Mick Jagger, Keith Richards)].

PMID- 9630794
TI  - [Important to understand and manage reactions of people with problems connected
      to amalgam and electricity].

PMID- 9630795
TI  - [Misdiagnosis of children with autism may cause many problems].

PMID- 9630796
TI  - [Nothing new under the sun].

PMID- 9630797
TI  - [Laparoscopic surgery--a comment].

PMID- 9630798
TI  - [Neurologist, otolaryngologist...? Which specialist should treat facial pain?].
AB  - Pain is a major public health problem. The management of orofacial pain may be a
      difficult challenge to the medical and dental professions. Ideally, severe cases
      of this type of pain should be treated by a team drawn from several disciplines
      such as neurology, otolaryngology, dentistry and psychiatry. Trigeminal neuralgia
      patients develop brief, very severe unilateral pain, usually radiating from the
      upper or lower jaw toward the ear, and confined to the distribution of the
      trigeminal nerve. The pain may be triggered by chewing, shaving or exposure to
      cold wind. Most patients respond to carbamazepine, with phenytoin or baclofen as
      an alternative. Intractable pain may require surgical treatment. Horton's
      syndrome (cluster headache) is always unilateral and is often associated with
      unilateral lacrimation and rhinorrhoea. The pain is extreme, and its typical
      localisation the eye, forehead, temple, jaws, or teeth. Treatment with ergotamine
      and sumatriptan has been used with some success, calcium blockers (e.g.,
      verapamil) being used as prophylaxis. Atypical facial pain is a continuous ache
      with intermittent episodes, localised to non-muscular, non-joint facial areas.
      The pain may be unilateral or bilateral, and may persist for many years.
      Typically, these patients consult a variety of specialists, such as dentists and
      otolaryngologists. Surgical procedures such as tooth extraction or sinus surgery,
      even if skillfully executed, exacerbate the condition, are are thus
      contraindicated. If the patient does not respond to reassurance, antidepressants
      may be tried. In sinusitis, the pain location is dependent upon which paranasal
      sinus is affected. Routine diagnostic nasal endoscopy and coronal plane computed
      tomography enable subtle pathological changes that are related to chronic pain to
      be identified. If medical treatment fails to afford relief, surgery should be
      considered. Pain, limited range of jaw motion, and joint noises are the common
      characteristics of temporomandibular disorders. Treatment usually consists of non
      surgical means such as splints, occlusal equilibration, and non-steroidal anti
      inflammatory drugs. Surgical treatment is indicated in a few carefully selected
      cases. Most dental pain is attributable to caries or periodontal disease. When
      pus is present, drainage affords excellent pain relief. Acute pericoronitis
      involving mandibular third molars responds to irrigation, removal of maxillary
      third molar trauma, and--in cases of serious infection--antimicrobial therapy.
      Early recognition of a case of chronic pain improves the chances of successful
      management, and avoids frustration and disillusion both to patient and doctor.

PMID- 9630799
TI  - [Transplantation of islets of Langerhans in type 1 diabetes. Three cases treated
      in Sweden to date].
AB  - The article consists in a report of the first three cases of human islet
      transplantation to have been carried out in Sweden. Cadaveric pancreatic glands
      were harvested and flown to the islet transplantation laboratory at the
      University of Giessen in Germany. After isolation, the islets were returned to
      Huddinge Hospital in Stockholm. The recipients were diabetic renal transplant
      patients, who received 5,000-8,000 islets by intraportal injection. Initially
      blood glucose levels were stabilised and HbA1c levels normalised, but no patient
      became insulin independent. After a few months serum C-peptide levels diminished,
      and after 6-10 months were undetectable. Islet function loss is probably to be
      explained by rejection and cytomegalvirus infection. In future cases new improved
      immunosuppressive protocols will be implemented.

PMID- 9630800
TI  - [Arteriosclerosis caused by infection? A possible link between Chlamydia
      pneumoniae and atherosclerosis].
AB  - Infection as a possible underlying cause of atherosclerosis has aroused
      increasing interest in recent years, Chlamydia pneumoniae being one of the
      organisms upon which attention has been focused. Newly published results of
      antibiotic treatment of vascular disease not only appear to provide further
      support for the infection hypothesis, but also suggest a quite different approach
      to the treatment of atheromatous cardiovascular disease. However, confirmatory
      clinical trials will be needed before antibiotic treatment can be considered in
      such cases.

PMID- 9630801
TI  - [Proposed criteria for diagnosis of celiac disease in children].
AB  - At a seminar arranged in September 1997 by the Swedish Paediatric Working Group
      for Coeliac Disease, a diagnostic protocol proposed by the working group was
      approved by a majority of the paediatricians present, representing almost all
      paediatric units in Sweden. Briefly, a small bowel biopsy is called for in all
      children, both at presentation and as a control during gluten-free dieting.
      Subsequent gluten challenge and biopsy are mandatory only in cases of atypical
      presentation or if the diagnosis is questioned at some future date. Serum
      antigliadin and anti-endomysial antibody tests are complementary tools. Agreement
      was also reached regarding the institution of a national coeliac disease
      registry.

PMID- 9630802
TI  - [Migration medicine in primary health care--somatic and mental symptoms].

PMID- 9630803
TI  - [Angiogenesis inhibitors in advanced cancer. Many current clinical trials show
      promising results].
AB  - Tumour growth and metastasis are dependent on angiogenesis, the formation of new
      blood vessels. In experimental models, tumour regression can be induced by the
      administration of specific angiostatic agents. The inhibition of angiogenesis
      represents a new approach in cancer therapy. Specific inhibition of angiogenesis
      is not characterised by the typical dose-limiting toxicity of chemotherapy. By
      targeting the untransformed and genetically stable vascular endothelium, drug
      delivery is no problem, and angiostatic therapy is not associated with the
      development of drug resistance. However, the treatment has to be continued for
      months or years, and some angiostatic agents are known to interfere with
      fertility. Approximately thirty angiostatic agents are undergoing clinical
      trials, and another fifty agents preclinical testing. Since the clinical trials
      are performed on patients with advanced tumours intractable to conventional
      therapy, and as the test drugs are first generation angiostatic agents, their
      effect is measured in terms of delay in tumour progression or reduction in values
      for surrogate endpoints such as tumour markers. In this article, based on reports
      presented at a recent international conference on angiogenesis antagonists, a few
      angiostatic agents are reviewed with brief comments on their performance in early
      clinical trials, and some new and promising angiostatic strategies are outlined.

PMID- 9630804
TI  - [Was it the "man on the scale" who first understood the benefit of motion?].

PMID- 9630805
TI  - [One more African case of abdominal pregnancy].

PMID- 9630806
TI  - [Demand for cesarean section by the mother was of significance. Compensation for
      anoxic injury even if no error was made].

PMID- 9630807
TI  - [Bronchial hyperreactivity is not always asthma].

PMID- 9630808
TI  - [What did Beethoven die of?].

PMID- 9630809
TI  - [Medical engineering. From visions of a happy society to a nightmare].

PMID- 9630810
TI  - [The moment of truth for physicians on vacation].

PMID- 9630811
TI  - [Cerebral hemodynamics during implantation of cardioverter-defibrillator
      systems].
AB  - OBJECTIVE: During ICD-implantation it is necessary to prove the function and to
      determine the optimal threshold by means of induced ventricular fibrillation
      (VF). Provoked cardiac arrests cause a circulator stop of the cerebral perfusion.
      Our aim was to examine the changes of cerebral blood flow velocity (CBFV(MCA))
      after induced VF depending on the duration of fibrillation and prior values of
      CBFV(MCA). PATIENTS AND METHODS: Sixty induced episodes of VF in 9 patients (mean
      age +/- SD 53.5 +/- 8 years) were examined during ICD-implantation. Beside the
      standardized anaesthesiological monitoring, transcranial Doppler sonography was
      used to record the cerebral blood flow velocity in the middle cerebri artery
      CBFV(MCA). The duration of the fibrillation-period and the range and duration of
      the CBFV increase during the post defibrillation-period were correlated.
      Additionally, we examined whether systematic differences existed between the
      episodes of each patient (time-trend) by means of 5 following episodes of a
      patient. RESULTS: During all episodes of VF and hyperperfusion was present, that
      means a time interval showing increased values of CBFV(MCA), compared to the
      values present before VF. The duration of hyperperfusion depended significantly
      on the fibrillation time (r = 0.57; p < 0.001). The equation of regression is:
      hyperperfusion time = 11.1 + 1.22 x fibrillation time. The amount of
      hyperperfusion, that means the maximal CBFV after defibrillation, increase
      significantly with CBFV(MCA) before VF (correlation = 0.88; p < 0.001). The
      equations of regression is hyperperfusion height = 6.11 + 1.22 x CBFV(MCA) before
      VF. The duration of hyperperfusion is not influenced by the maximal CBFV(MCA)
      after defibrillation (r = 0.08; p = 0.52). In the examined patients no
      significant differences in the hyperperfusion time maximal CBFV(MCA) after
      defibrillation between the episodes were found. CONCLUSION: After induced VF you
      always have to expect a reactive cerebral hyperperfusion. The amount of increase
      of CBFV after defibrillation depends on the prior values of CBFV before
      fibrillation and shows a nearly proportional relation to these. The duration of
      hyperperfusion shows a linear dependency on VF-times. This may show that we had
      VF-times, in which the cerebral autoregulation and other cerebral physiological
      reactions compensate the drop of the CBFV(MCA) during VF in the postfibrillation
      time. In further studies will be examined if there are similar changes in the
      cerebral metabolism as in CBFV(MCA).

PMID- 9630812
TI  - [Emergency heart valve replacement after acute cerebral embolism during florid
      endocarditis].
AB  - BACKGROUND: The indication for urgent cardiac surgical interventions in patients
      with active infective endocarditis has to be considered carefully following
      thromboembolic events, because of the high recurrence rate of such complications.
      In the case of brain embolisms the prognostic benefit of urgent surgery has been
      discussed controversially as effective anticoagulation during open heart surgery
      may result in secondary cerebral hemorrhages. PATIENTS AND METHODS: Between 1978
      and 1993 infective endocarditis (IE) was proven in 288 consecutive and
      prospectively followed patients (131 females, 157 males; mean age 53.6 +/- 8.7 [9
      to 81] years). To analyze potential benefits and risks of an urgent surgical
      intervention early after embolic cerebral infarction, cumulated survival rates
      were calculated for patients with and without surgical intervention with special
      reference to incremental risk factors and the timing of surgery. RESULTS: In 50
      patients (17.4%) the clinical course was complicated by one, and in 58 patients
      (20.2%) by recurrent embolic events. In 80% the first embolism occurred within 33
      days following the first manifestation of typical signs and symptoms of IE. 80%
      of recurrent events were observed within 32 days following the initial embolism.
      71% of all embolic events were cerebral. In patients with cerebral embolism
      corroborated by computed tomography (CCT), the clinical course was complicated by
      intracranial hemorrhage in 12.5% while it was only 1.5% for patients without
      cerebral embolism. Because of a lack of therapeutic alternatives, 22 of 49
      patients with recurrent embolic events, of which at least one was cerebral,
      underwent urgent cardiac surgery within 4 to 366 hours after the first cerebral
      manifestation. The cumulated survival rate of patients operated within 72 hours
      after the initial cerebral embolism was significantly more favorable (p < or =
      0.000) than for unoperated patients or those who were operated after more than 8
      days. CONCLUSION: An embolic event during IE carries a more than 50% risk of
      recurrence. In patients with short duration of signs and symptoms of IE and
      postembolic echocardiographic demonstration of persistent vegetations the
      probability is > 80%. At least for those patients urgent surgical intervention to
      remove the source of infection and embolic hazard seems to be beneficial.
      Surgical intervention using the heart-lung-machine should be performed within 72
      hours. Such early timing results in a significant lower rate of secondary
      cerebral hemorrhages (p < or = 0.00) than a postponed operation. To exclude early
      reperfusion hemorrhage due to spontaneous thrombus fragmentation, CCT should be
      repeated directly preoperatively.

PMID- 9630813
TI  - [Significance of galenic preparations for luminal release of 5-aminosalicylic
      acid in human small intestinal lumen].
AB  - BACKGROUND: Sufficient intraluminal concentrations of 5-aminosalicylic acid (ASA)
      within inflamed regions of the intestine are required for therapeutic efficacy in
      inflammatory bowel disease. Various oral delayed release preparations have been
      developed to ensure that 5-ASA is set free in those parts of the gut, which are
      most frequently affected. However, resulting intraluminal concentrations within
      the small bowel are unknown. Therefore, we determined and compared 5-ASA release
      within different segments of the small bowel from an Eudragit L coated 5-ASA
      preparation (Salofalk) and from an ethylcellulose coated microsphere preparation
      (Pentasa). METHODS: Twelve healthy subjects were intubated with an oro-ileal
      multilumen-tube for marker perfusion, duodenal, jejunal and ileal aspiration of
      chyme and intestinal manometry. Each subject received 500 mg 5-ASA (Salofalk, n =
      6, or Pentasa, n = 6) together with a semiliquid test meal. Intestinal aspirates,
      blood and urine samples were obtained in regular intervals for 7 to 10 hours and
      were analysed for 5-ASA and its main metabolite acetyl-5-ASA by HPLC. RESULTS:
      With Salofalk, gastric emptying of 5-ASA did not take place in the digestive, but
      in the subsequent interdigestive period. Luminal delivery of 5-ASA and acetyl-5
      ASA increased from the duodenum (3% of dose) to the ileum (30% of dose). 10% of
      the dose administered were excreted in urine and about 90% reached the colon
      unreleased or solubilised. By contrast, with Pentasa, 5-ASA was delivered to the
      duodenum together with the test meal and released continuously throughout the
      small intestine (about 20% of dose solubilised at each intestinal site). Only
      3.5% of the dose administered were excreted in urine. Deliver of 5-ASA to the
      colon was equal to Salofalk. CONCLUSIONS: From both preparations, considerable
      amounts of 5-ASA are released during small intestinal transit thus explaining
      therapeutic efficacy in small intestinal Crohn's disease. Because of specific
      release patterns, Salofalk may be of use especially in terminal ileal disease,
      where as patients with extensive small intestinal disease including the proximal
      small intestine might benefit from Pentasa.

PMID- 9630814
TI  - [The human kidney as an important producer of glucose].
AB  - BACKGROUND: According to current textbook knowledge the liver is the exclusive
      site of glucose production in postabsorptive humans. Although many animal and in
      vitro data have documented that the kidney is capable of gluconeogenesis,
      production of glucose by the human kidney has been regarded as negligible to
      date. This traditional perception is based on methodologically inadequate net
      balance studies, which other than after a prolonged fast or during metabolic
      acidosis showed no significant net renal glucose release. STUDIES: Recent tracer
      studies, however, showing a renal glucose production accounting for 25% of
      systemic glucose production, have refuted this view. glucose production by the
      human kidney is stimulated by epinephrine and inhibited by insulin. Glucagon
      stimulates hepatic but not renal glucose production. The most important renal
      gluconeogenic precursors are lactate, glutamine and glycerol. The implications of
      these recent findings on the understanding of the physiology and pathophysiology
      of human glucose metabolism are discussed. CONCLUSION: Magnitude and regulation
      of renal glucose production have important consequences for the intermediary
      metabolism, counterregulation of hypoglycemia, glucose metabolism of uremia and
      the pathophysiology of type I and type II diabetes.

PMID- 9630815
TI  - [Mycotic aneurysm in endocarditis lenta as the etiology of intraparenchymatous
      cerebral hemorrhage].
AB  - CASE REPORT: A 49-year-old male was admitted for left-side headache and mild
      speech defect. Clinical examination showed a pansystolic murmur of mitral
      regurgitation and mild Wernicke aphasia. In laboratory studies ESR and CRP were
      increased. Computed tomography of brain revealed a left temporoparietal hematoma.
      Echocardiographic examination demonstrated vegetations and mitral valve
      perforation. In blood cultures grew alpha-streptococci. Cerebral angiography was
      performed and a fusiform aneurysm on a distal branch of the left middle cerebral
      artery was identified. Follow-up angiography showed a total resolution of the
      aneurysm after 6 weeks of intravenous antibiotics. CONCLUSION: This case
      demonstrate that patients with intracerebral hematomas associated with infectious
      endocarditis should be investigated for mycotic intracranial aneurysm.

PMID- 9630816
TI  - [A young patient with multiple arterial occlusions].
AB  - BACKGROUND: Mild hyperhomocysteinemia due to genetic causes and nutrition factors
      is well known as an independent strong risk factor for premature arterial
      occlusive disease. CASE REPORT: A 27-year-old female with a history of two
      episodes of small bowel ileus due to vascular causes presented with subacute pain
      in the left lower extremity. Angiography revealed a short segmental occlusion in
      the P III segment of the popliteal artery with small vessel collateralization and
      proximal occlusion of the superior mesenteric artery und the coeliac trunk.
      Vascular risk factors in this patient included smoking over a duration of 10
      years, use of oral contraceptives (estrogen and gestagen combination) and
      elevated levels of homocysteine in the fasting state and after methionin loading.
      The patient was treated conservatively with intravenous application of
      prostaglandins, additionally she underwent training to improve her walking
      capability. After 4 weeks of the fasting state as well as after methionin loading
      were normalized by an oral substitution with folate and B vitamins. So far it was
      not possible to prove a genetic defect of the enzymes participating in the
      metabolism of homocysteine. CONCLUSION: This clinical conference of a young
      female patient with occlusion of several arteries illustrates the differential
      diagnosis of premature occlusive vascular disease with special regard to mild
      hyperhomocysteinemia as an independent risk factor.

PMID- 9630817
TI  - [Supraventricular tachycardia, IV: Atrial tachycardia--diagnosis, mechanisms and
      therapy].

PMID- 9630818
TI  - [Thoracic pain and bulky mass in the thoracic wall].

PMID- 9630819
TI  - [Maintaining hope by terminal cancer patients. An empirical introspection for
      general practice from the retrospective viewpoint of an internal medicine
      oncologist].

PMID- 9630821
TI  - 50th AACC Annual Meeting, Chicago, Illinois, USA. August 2-6, 1998. Abstracts.

PMID- 9630820
TI  - [Costs and fees in health care. Evaluation and assessment by cardiological
      patients].
AB  - PATIENTS AND METHOD: In a pilot study 70 patients treated in the Department of
      Cardiology were asked to asses the cost of coronary angiography, PTCA, heart
      transplantation, pacemakers and prosthetic heart valves. Salaries of physicians
      and nurses should be estimated, and causes of increase of costs in health care be
      defined. RESULTS: 91.7% patients criticized health care as too expensive but
      reasonable with regard to output and efficacy. As most important reasons for
      increase of cost were given "expensive drugs" (70.6%), "great number of drugs"
      (56.9%) and "increased number of old patients" (56.9%). Costs of coronary
      angiography were overestimated (twice) and those of PTCA were underestimated
      (half). Two thirds of the patients guessed the price of pacemakers and prosthetic
      heart valves much to low. Salaries of physicians had been estimated near the
      upper reference value, those of nurses near the lower reference value.
      CONCLUSION: Most of our patients were insufficiently informed about costs in
      health care. Clarification and more transparency are needed.

PMID- 9630822
TI  - What are narrow therapeutic index drugs?

PMID- 9630823
TI  - Effect of CYP3A inhibition on vesnarinone metabolism in humans.
AB  - OBJECTIVE: To identify the cytochrome P450 (CYP) enzymes involved in the
      conversion of vesnarinone to it main primary metabolite OPC-18692 and to
      investigate the effect of CYP3A inhibition on the pharmacokinetics of vesnarinone
      in vivo. METHODS: Formation of the primary vesnarinone metabolite OPC-18692 was
      measured in microsomes from AHH-1 TK +/- cells heterologously expressing CYP1A1,
      CYP1A2, CYP2A6, CYP2C9, CYP2D6, CYP2E1, or CYP3A4. The pharmacokinetics of
      vesnarinone and OPC-18692 were defined for 12 health white men after oral
      administration of 60 mg vesnarinone before and after CYP3A inhibition, which was
      produced by pretreatment with erythromycin. CYP3A inhibition was verified with
      erythromycin breath test. RESULTS: In vitro, expressed CYP2E1 and CYP3A4 produced
      significant amounts of OPC-18692 with the higher formation rate observed by
      CYP3A4 (12.3 pmol/pmol VYP3A4 per 2 hours versus 1 pmol/pmol CYP2E1 per 2 hours).
      In vivo, the area under the concentration-time curve extrapolated to infinity
      (AUC[infinity]) of vesnarinone after pretreatment with erythromycin increased
      from 133 +/- 26 micrograms.hr/ml to 202 +/- 47 micrograms.hr/ml (p < 0.001), and
      the half-life increased from 36.5 +/- 9.6 hours to 46.2 +/- 9.2 hours (p < 0.01).
      Clearance decreased from 372 +/- 68 ml/min to 256 +/- 49 ml/min (p < 0.001).
      These changes in the disposition of vesnarinone were accompanied by a decrease in
      plasma concentration of the metabolite OPC-18692 so that the AUC(0-48) was
      reduced from 1311 +/- 513 micrograms.hr/ml to 850 +/- 148 micrograms.hr/ml (p <
      0.001). The total amount of vesnarinone excreted in the urine up to 168 hours
      after administration increased after erythromycin pretreatment (p < 0.001).
      Although renal clearance did not change, OPC-18692 was not detectable in the
      urine. The erythromycin breath test showed significant inhibition after
      pretreatment with erythromycin (p < 0.001). CONCLUSIONS: CYP2E1 and CYP3A4 are
      involved in the phase I metabolism of vesnarinone. Inhibition of CYP3A activity
      in vivo increases the plasma concentration of vesnarinone and delays its
      elimination in humans so that monitoring of its plasma levels may be helpful in
      preventing concentration-related toxicity when CYP3A activity is impaired.
      Whether CYP3A induction and altered CYP2E1 activity may also change the in vivo
      disposition of vesnarinone remains to be determined.

PMID- 9630824
TI  - The pharmacokinetics of a single oral dose of mycophenolate mofetil in patients
      with varying degrees of renal function.
AB  - BACKGROUND: The purpose of this study was to determine the effect of renal
      function on the elimination and disposition of mycophenolic acid and its
      glucuronide metabolite (MPAG) after oral administration of the pro-drug
      mycophenolate mofetil. In addition, this study sought to examine hemodialysis
      removal of mycophenolic acid and its MPAG. METHODS: Subjects were stratified into
      five groups on the basis of iohexol clearance. After an overnight fast, all
      subjects received a single 1 gm dose of mycophenolate mofetil. Plasma
      concentrations of mycophenolic acid and MPAG were measured from 0 to 96 hours
      after administration. Mycophenolic acid and MPAG maximum plasma concentration
      (Cmax) and the time to reach Cmax (tmax) for each group were determined from the
      mean plasma concentration-time profiles. Area under the plasma concentration-time
      curve values for mycophenolic acid and MPAG were calculated by the trapezoidal
      rule. The half-lives of mycophenolic acid and MPAG were calculated from the
      terminal portions of the concentration-time profiles. RESULTS: Mycophenolic acid
      clearance was not associated with changes in glomerular filtration rate (GFR).
      Cmax tended to increase as GFR declined. MPAG clearance correlated well with GFR
      (r2 = 0.905). Clearance of mycophenolic acid and MPAG were unaffected by
      hemodialysis. CONCLUSIONS: Clearance of mycophenolic acid after a single 1 gm
      oral dose of mycophenolate mofetil is unaffected by renal function. Clearance of
      mycophenolic acid is unaffected by hemodialysis. Diminished renal function should
      not require preemptive adjustment of 1 gm doses of mycophenolate mofetil; however
      dosage adjustment may be warranted on the basis of adverse effects or toxicity in
      individual patients. Mycophenolate mofetil can be administered irrespective of
      hemodialysis session without effect on mycophenolic acid exposure.

PMID- 9630825
TI  - Metabolism of warfarin enantiomers in Japanese patients with heart disease having
      different CYP2C9 and CYP2C19 genotypes.
AB  - OBJECTIVE: To determine whether genetic polymorphism of cytochrome P450 (CYP) 2C9
      affects the in vivo metabolism of warfarin enantiomers. METHODS: Eighty-six
      Japanese patients heart disease who were given warfarin participated in the
      study. Plasma unbound concentrations of warfarin enantiomers and urinary (S)-7
      hydroxywarfarin concentrations were measured by means of a chiral HPLC and
      ultrafiltration technique to calculate the unbound oral clearance (CLpo,u) for
      the enantiomers and the formation clearance (CLm) for (S)-warfarin 7
      hydroxylation. Genotyping for CYP2C9 (the wild type [wt], Arg144/Cys, and
      I1e359/Leu) and for CYP2C19 (wt, ml, and m2) was performed with a polymerase
      chain reaction method. RESULTS: Three patients were heterozygous for the CYP2C9
      Leu359 mutation but none were homozygous for the mutation (the allele frequency
      of 0.017). None had a CYP2C9 Cys144 allele. The medians for (S)-warfarin CLpo,u
      and its 7-hydroxylation CLm obtained from heterozygotes of CYP2C9 Leu359 were
      significantly less than those obtained from homozygotes of the wt allele, as
      follows: 234 ml/min (range, 156 to 269 ml/min) versus 632 ml/min (range, 180 to
      2070 ml/min) (p < 0.001) and 0.20 ml/min (range, 0.05 to 0.77 ml/min) versus 0.80
      ml/min (range, 0.05 to 14.9 ml/min) (p < 0.05), respectively. In contrast, no
      difference was observed in (R)-warfarin CLpo,u between the groups. The allele
      frequencies for CYP2C19 m1 and CYP2C19 m2 were 0.26 and 0.14, respectively,
      indicating 15% of patients were genotypically poor metabolizers of CYP2C19. No
      difference in CLpo,u for warfarin enantiomers was observed between the assumed
      CYP2C19 phenotypes. CONCLUSION: Heterozygotes for CYP2C9 I1e359/Leu allele have
      reduced in vivo metabolism of (S)-warfarin but not (R)-warfarin. Because (S)
      warfarin has a greater anticoagulant potency than its (R)-congener, the genetic
      polymorphism of CYP2C9 may partly account for the large interpatient variability
      in therapeutic dosages of warfarin.

PMID- 9630826
TI  - Influence of CYP2D6 polymorphism on the pharmacokinetics and pharmacodynamic of
      tolterodine.
AB  - OBJECTIVE: To determine whether cytochrome P450 2D6 (CYP2D6) is involved in the
      metabolism of tolterodine by investigating potential differences in
      pharmacokinetics and pharmacodynamic (heart rate, accommodation, and salivation)
      of tolterodine and its 5-hydroxymethyl metabolite between poor metabolizers and
      extensive metabolizers of debrisoquin (INN, debrisoquine). METHODS: Sixteen male
      subjects (eight extensive metabolizers and eight poor metabolizers) received 4 mg
      tolterodine by mouth twice a day for 8 days followed by a single intravenous
      infusion of 1.8 mg tolterodine for 30 minutes after a washout period. Doses were
      given as the tartrate salt. The pharmacokinetics of tolterodine and 5
      hydroxymethyl metabolite were determined, and the pharmacodynamic were measured.
      RESULTS: The mean systemic clearance of tolterodine was significantly lower (p <
      0.001) among poor metabolizers (9.0 +/- 2.1 l/hr) compared with extensive
      metabolizers (44 +/- 13 L/hr), resulting in a fourfold longer elimination half
      life (p < 0.001). The terminal half-life of the 5-hydroxymethyl metabolite (2.9
      +/- 0.4 hours) was slightly longer than that of the parent compound (2.3 +/- 0.6
      hours) among extensive metabolizers, but the 5-hydroxymethyl metabolite was
      undetectable in the serum of poor metabolizers. Only minor differences in
      pharmacodynamic effects after tolterodine dosage were observed between the
      groups. Tolterodine caused a similar decrease in salivation in both panels. The
      decrease occurred when the concentration of unbound tolterodine and 5
      hydroxymethyl metabolite among extensive metabolizers was comparable with that of
      tolterodine among poor metabolizers. CONCLUSIONS: Tolterodine is extensively
      metabolized by CYP2D6 with high specificity. Despite the effect on
      pharmacokinetics, the CYP2D6 polymorphism does not appear to be of great
      importance in the antimuscarinic effect, probably because of the additive action
      of parent drug and active metabolite.

PMID- 9630827
TI  - Quantitation of three-month intraindividual variability and influence of sex and
      menstrual cycle phase on CYP1A2, N-acetyltransferase-2, and xanthine oxidase
      activity determined with caffeine phenotyping.
AB  - OBJECTIVE: To evaluate intraindividual variability and the effects of sex and
      menstrual cycle phase on the activity of cytochrome P450 1A2 (CYP1A2), N
      acetyltransferase 2 (NAT2), and xanthine oxidase. METHODS: Ten white men were
      given 2 mg/kg caffeine orally every 14 days for 3 months. The same dosage of
      caffeine was given to 10 premenopausal white women during the midfollicular and
      midluteal phases of three complete menstrual cycles. Phenotype was determined
      with urinary caffeine metabolite ratios. RESULTS: For CYP1A2, mean metabolic
      ratio (+/- SD) was 5.97 +/- 2.78 during the midfollicular phase and 5.32 +/- 1.99
      during the midluteal phase (p = 0.2). For extensive and poor metabolizer of NAT2.
      Mean midfollicular phase metabolite ratios were 0.71 +/- 0.060 and 0.37 +/-
      0.030, and mean midluteal phase metabolite ratios were 0.69 +/- 0.076 and 0.39 +/
      0.053 (p = 0.9). For xanthine oxidase, mean midfollicular phase metabolite ratio
      was 0.63 +/- 0.06 and mean midluteal phase metabolite ratio was 0.63 +/- 0.05 (p
      = 0.3). Among the men, mean CYP1A2, NAT2 rapid and slow acetylator, and xanthine
      oxidase indices were 9.42 +/- 10.18, 0.66 +/- 0.021, 0.31 +/- 0.056, and 0.64 +/-
      0.03. There were no differences in metabolite ratios between men and women for
      CYP1A2, NAT2 extensive metabolizers, or xanthine oxidase. A statistically
      significant sex difference was found for poor metabolizers of NAT2 (p < 0.05).
      Median coefficients of variation for CYP1A2, NAT2 extensive and poor
      metabolizers, and xanthine oxidase ratios were 16.8% (range, 4.5% to 49.3%), 2.9%
      (range, 2.2% to 4.7%), 13.4% (range, 7.5% to 27.2%), and 4.5% (range, 2.3% to
      13.0%). CONCLUSION: Stratification by menstrual cycle phase or sex need not be
      performed for pharmacokinetic or clinical investigations of substrates for
      CYP1A2, NAT2, or xanthine oxidase in which the subject are adults.

PMID- 9630828
TI  - Pharmacokinetics and the pharmacodynamic action of midazolam in young and elderly
      patients undergoing tooth extraction.
AB  - OBJECTIVE: To determine whether age-dependent pharmacokinetic and pharmacodynamic
      alterations account for a more pronounced response to benzodiazepines among
      elderly patients. METHODS: Twelve young patients and 10 elderly patients received
      an intravenous dose of 0.05 or 0.03 mg/kg midazolan, respectively, before third
      molar extraction. Postoperative pain was treated with 30 mg dihydrocodeine. Serum
      concentrations of midazolam and sedative effects were monitored with visual
      analog scales and choice reaction time measurements for 6 hours. Test values
      above baseline were integrated, and pharmacokinetic-pharmacodynamic analysis was
      performed. Heart rate, blood pressure, arterial oxygen saturation, and amnesia
      also were assessed. RESULTS: There were no significant age-dependent differences
      in disposition of midazolam between young and elderly patients (apparent volume
      of distribution, 1.3 +/- 0.2 versus 1.1 +/- 0.4 L/kg; halflife, 3.3 +/- 1.5 hours
      versus 3.7 +/- 2.2 hours; total body clearance, 451 +/- 186 ml/min versus 343 +/-
      137 ml/min). However, higher values of area under the effect curve (AUEC) and
      AUEC divided by area under the serum concentration-time curve (AUC) (sensitivity
      index) were observed among the elderly as follows: AUEC for reaction time
      (AUECRT) (573 versus 261; p = 0.042), AUEC for visual analog scale (AUECVAS)
      (37.7 versus 14.4; p = 0.011), AUECRT/AUC (6.3 versus 1.8; p = 0.007), and
      AUECVAS/AUC (0.40 versus 0.11; p = 0.009) compared with the young group.
      Likewise, mean concentration at half-maximal effect for sedation was lower (p =
      0.025) among older patients (20.5 +/- 2.2 ng/ml) than among younger (29.7 +/- 6.6
      ng/ml) patients. Amnesia was observed among 86% of patients and oxygen saturation
      was always 95% or more of basal value. There were no age-related differences in
      concentration of dihydrocodeine and its active metabolite dihydromorphine, but
      dihydromorphone levels were much lower in there intermediate metabolizers (455 to
      879 fmol/l) and especially in five poor metabolizers (65 to 498 fmol/L) than
      among extensive metabolizer of cytochrome p450 2D6 (1604 to 6490 fmol/L).
      CONCLUSION: Elderly patients are more sensitive to the sedative action of
      midazolam than young patients, and the sensitivity is caused by age-dependent
      pharmacodynamic alterations. The age-adjusted doses used are both effective (for
      sedative amnesia) and safe (in terms of arterial oxygen saturation, heart rate,
      and blood pressure.

PMID- 9630829
TI  - Therapeutic and diagnostic potential of a vasopressin-2 antagonist for impaired
      water handling in cirrhosis.
AB  - OBJECTIVE: Progressive cirrhosis is associated with increasing difficulty to
      handle free water. We examined the therapeutic potential of an orally active
      nonpeptide vasopressin-2 receptor antagonist (OPC-31260) in the management of
      edema and ascites in patients with cirrhosis. By means of its chemical blockade
      of the vasopressin-2 receptor in the kidney, we also assessed the ability of
      renal water handling in the early stage of cirrhosis. METHODS: A single 30 mg
      dose of OPC-31260 was administered orally to eight biopsy-proven patients with
      cirrhosis who had ascites or peripheral edema. The aquaretic responses were
      compared with those in six healthy subjects. RESULTS: In the patients with
      cirrhosis, OPC-31260 significantly (p < 0.01) increased the urinary excretion
      rate at 0 to 2 hours, and significantly (p < 0.01) lowered urine osmolality at 2
      to 4 hours after administration. Free water clearance increased from -0.48 +/-
      0.14 to +0.19 +/- 0.21 ml/min (p < 0.05) at 0 to 4 hours after administration.
      However, these aquaretic responses in the patients with cirrhosis were only
      approximately half the responses observed in the healthy subjects. A significant
      (p < 0.05) inverse relationship was observed between indocyanine green retention
      at 15 minutes after administration and the maximal free water clearance after
      administration to the patients with cirrhosis. Urinary sodium excretion did not
      change significantly in the patients, whereas it increased twofold in the healthy
      subjects. Urinary vasopressin excretion tended to increase in the patients,
      whereas it increased twofold to threefold (p < 0.01 to 0.05) from the baseline in
      the healthy subjects. Urinary prostaglandin E2 excretion was not increased, and
      serum sodium and plasma vasopressin levels were elevated only slightly in both
      groups. CONCLUSIONS: Even though a hyporesponsiveness was observed in the group
      of patients with cirrhosis compared with the healthy group, the novel vasopressin
      2 antagonist induced hypotonic diuresis in patients with cirrhosis, suggesting a
      therapeutic potential in managing water excess. This drug response may be a new
      index to assess impairment of water handling in patients with cirrhosis.

PMID- 9630830
TI  - Effects of tobacco smoking and abstinence on middle latency auditory evoked
      potentials.
AB  - OBJECTIVE: To evaluate the effects of tobacco cigarette smoking and overnight
      abstinence on middle latency auditory evoked potentials among smokers and
      nonsmokers. METHODS: Groups of 9 to 10 adult male and female nonsmokers and
      smokers participated in the study. Each person volunteered for two laboratory
      sessions conducted in the early afternoon on 2 separate days. Smokers abstained
      from tobacco products 6 to 15 hours before the abstinent session and maintained
      their usual smoking behavior before the smoking session. The nonsmokers had a
      similar laboratory experience but sham smoked by means of inhaling air. Middle
      latency auditory evoked potentials were recorded from Cz to both ears as
      reference. RESULT: The latencies of the Na and Pa potentials during the smoking
      session were significantly (p < 0.01) shorter than those in abstinent smokers and
      nonsmokers. After smoking, peak-to-trough amplitudes for the V-Na, Na-Pa, and Pa
      Nb potentials were larger than those after abstinence and significantly larger
      than those among nonsmokers. CONCLUSIONS: The shorter latencies of the middle
      latency brain wave components in the smoking session suggest faster processing of
      sensory information after cigarette smoking. Larger Pa amplitudes after cigarette
      smoking suggest a higher arousal level than that among partially abstinent
      smokers and nonsmokers.

PMID- 9630831
TI  - Treatment of osteoarthritis with aspartame.
AB  - OBJECTIVE: The binding of sweet-tasting compounds in a human (Mcg) Bence-Jones
      dimer has been characterized by x-ray crystallography. Aspartame binding in this
      immunoglobulin fragment is remarkable. Unexpected pain relief noted by A.B.E., a
      crystallographer with diagnosed osteoarthritis, suggested that the accommodation
      of aspartame in the active site of the dimer may represent surrogate binding by
      other proteins, with analgesia as the outcome. METHODS: X-ray analysis of the
      complex of aspartame and the Bence-Jones dimer was conducted with crystalline Mcg
      protein and pure aspartame. A single-blind (n = 1) study to confirm analgesia was
      completed by administration of aspartame to A.B.E. A controlled double-blind
      trial was performed in patients with x-ray-documented osteoarthritis. Pain and
      performance changes were evaluated with use of two doses of placebo and two doses
      of aspartame. Effects on bleeding time were then evaluated by determination of
      template bleeding times in 34 normal volunteers. Finally, antipyretic effects
      were studied in Sprague-Dawley rats given intramuscular turpentine injections.
      RESULTS: Aspartame binding in the Bence-Jones dimer was verified by x-ray
      crystallography. Improvements in performance and pain relief were observed in
      A.B.E. at p < 0.001. Decreased pain and improved performance were also observed
      in patients with osteoarthritis (p < 0.001). Mild antihemostatic responses were
      observed in bleeding times after aspartame treatment. Modified template bleeding
      times increased at p < 0.01. Aspartame blocked the turpentine-mediated febrile
      responses in the treated rats (p < 0.01). CONCLUSIONS: L-Aspartyl-L-phenylalanine
      methyl ester is biologically active and appears to relieve pain, induce mild
      antithrombotic effects in humans, and decrease fever in animals.

PMID- 9630832
TI  - Cancer recurrences and secondary primary cancers after use of antihistamines or
      antidepressants.
AB  - OBJECTIVES: Reports in the scientific literature have described accelerated tumor
      growth in association with antidepressant and antihistamine exposure in
      experimental rodent cancer models. This study was designed to determine whether
      exposure to prescription antidepressants or antihistamines is associated with
      tumor growth in humans. METHODS: Two nested case-control studies were conducted
      with a cohort of 1467 patients with breast cancer, colon cancer, or melanoma
      diagnosed between 1988 and 1994. Eligible patients included 95 with a cancer
      recurrence and 78 with a second primary lesion diagnosed during the follow-up
      period. Five control subjects were matched to each case patient according to
      cancer site, stage, and follow-up time. Conditional logistic regression was used
      to compare risk for tumor recurrence or occurrence of a second primary tumor
      among patients using antidepressants or antihistamines with risk among unexposed
      patients. RESULTS: For a cohort of patients who were predominantly female (78%),
      with breast cancer (57%) and with a tumor in situ or with localized disease
      (79%), the average age was 62 years at cancer diagnosis and average duration of
      follow-up period was 2.2 years. Use of antidepressants or antihistamines was
      unrelated to risk for tumor recurrence (odds ratio, 0.97; 95% confidence
      interval, 0.52 to 1.78) or second primary tumors (odds ratio, 0.94; 95%
      confidence interval, 0.50 to 1.77). CONCLUSION: Typical use of antidepressant or
      antihistamine drugs did not increase risk for recurrent or second primary tumors
      among patients with cancer.

PMID- 9630833
TI  - Surgery of the trachea.

PMID- 9630834
TI  - Prolactin is an antagonist of TGF-beta activity and promotes proliferation of
      murine B cell hybridomas.
AB  - Prolactin (PRL) is an immunomodulator that has been demonstrated to enhance
      immune responses both in vitro and in vivo. Prolactin enhances the proliferative
      response of lymphoid cells to both nonspecific mitogens and specific antigens and
      increases their production of IL-2 and interferon-gamma. Studies were performed
      to examine whether recombinant human prolactin (r-hPRL) also acts as a growth
      factor for B cell hybridomas. Prolactin was able to stimulate proliferation of
      murine B cell hybridomas in a dose-dependent manner and enhanced their
      proliferation in response to IL-4, IL-5, and IL-6. This increase in proliferation
      resulted in an overall increase in antibody production. Studies were also
      undertaken to examine the effect of PRL with transforming growth factor beta (TGF
      beta), an immunosuppressive cytokine. Hybridoma cell lines incubated with TGF
      beta demonstrated a dose-dependent decrease in proliferation. Variability in the
      degree of inhibition was observed among the various hybridomas in their
      responsiveness to TGF-beta. The addition of r-hPRL to the cultures reversed the
      antiproliferative effects of TGF-beta. The mechanism by which PRL can overcome
      the anti-proliferative effect of TGF-beta is under investigation. These findings
      provide an additional rationale for using r-hPRL clinically in immunosuppressed
      patients in certain disease settings such as AIDS and cancer, where
      overexpression of TGF-beta has been implicated in disease development and
      progression.

PMID- 9630835
TI  - Long-lived protective immunity to Listeria is conferred by immunization with
      particulate or soluble listerial antigen preparations coadministered with IL-12.
AB  - The ability of IL-12 to promote the development of Th1-type immune responses, and
      thus promote cellular immunity, has been well documented. In a previous report,
      we showed that coadministration of IL-12 with heat-killed Listeria monocytogenes
      elicited intense antigen-specific T cell responses that conferred protective
      listerial immunity. Herein, we have extended those studies by demonstrating that
      multiple injections of heat-killed L. monocytogenes and IL-12 elicit memory
      responses that confer long-lived (> or = 3 months) protective immunity and that
      immunity can be transferred adoptively with cells from immunized mice injected
      into naive mice. These studies have also demonstrated that the powerful
      adjuvanticity of IL-12 is observed with soluble as well as particulate immunogens
      and is operative in mouse strains that have different MHC haplotypes. These
      findings suggest that IL-12 may be a useful adjuvant component of vaccines for a
      wide variety of pathogens in animal and human systems.

PMID- 9630836
TI  - Pentoxifylline potentiates nitric oxide production and growth suppression in
      interferon-gamma-treated L929 fibroblasts.
AB  - In this study the effects of the phosphodiesterase inhibitor pentoxifylline (PTX)
      on nitric oxide (NO) production and proliferation of murine fibrosarcoma cell
      line L929 were investigated. We showed that both IFN-gamma (200 U/ml)-induced NO
      production and inhibition of [3H]thymidine uptake by L929 cells were potentiated
      in a synergistic fashion in the presence of PTX (200 micrograms/ml). These
      effects of PTX could be a consequence of phosphodiesterase inhibition, since they
      were mimicked by cAMP analogue dibutyryl cAMP. PTX failed to affect NO production
      when added to cells in which inducible NO synthase (iNOS) had already been
      induced with IFN-gamma and any further induction was blocked by cycloheximide (1
      ug/ml), indicating that PTX modulates NO synthesis in L929 cells probably on a
      pretranslational level. Inhibition of iNOS with L-NAME (3 mM), although
      completely abolishing NO production, did not have any effect on proliferation of
      IFN-gamma or IFN-gamma + PTX-treated L929 cells, arguing against the possibility
      that growth suppression of these cells was due to the enhanced NO production.
      Moreover, the observation that the NO donor sodium nitroprusside (10-250 microM)
      significantly increased incorporation of [3H]thymidine in L929 fibroblasts
      suggests a role for NO in the positive regulation of their growth.

PMID- 9630837
TI  - Protection against diabetes by MHC heterozygosity and reversal by
      cyclophosphamide.
AB  - In type I diabetes in both rodents and humans, genetic susceptibility to disease
      is strongly linked to MHC class II alleles. In some cases, however, certain class
      II alleles provide resistance to disease. To examine this effect in a well
      defined system, we studied double transgenic mice expressing influenza
      hemagglutinin (HA) on pancreatic islet beta cells and an HA-specific TCR on CD4 T
      cells. On a susceptible B10.D2 background, 70% of double transgenic mice develop
      an early-onset spontaneous autoimmune diabetes. MHC heterozygosity induced
      variable protection from diabetes, depending on the specific nonpermissive
      allele, but insulitis was invariably present. Autoreactive T cells retained the
      ability to induce diabetes because cyclophosphamide treatment induced diabetes in
      81% of young MHC(d/b) transgenic mice, although the effect was diminished in
      older mice. Most importantly, treatment induced higher IFN-gamma/IL-4 ratios
      among CD4 T cells, suggesting a strong shift toward Th1 development, perhaps
      through direct effects on patterns of gene expression in CD4 T cells.

PMID- 9630838
TI  - Interleukin-10 reduces natural killer sensitivity and downregulates MHC class I
      expression on H-ras-transformed cells.
AB  - We examined the effect of IL-10 on sensitivity to NK-cell-mediated cytotoxicity
      of the H-ras-induced transformants, W14 and W31. Incubation of cells with
      recombinant human (rh) IL-10 resulted in a dose-dependent decrease in the
      expression of MHC class I antigens, but not in the ICAM-1 expression. However,
      prior incubation of W31 cells with rhIL-10 markedly decreased their
      susceptibility to cytolysis by rat splenic NK cells. This fact suggested that the
      IL-10-mediated decrease in MHC class I expression might not dominate the
      regulation of the NK sensitivity. This was true when rat IL-10 cDNA-introduced
      W31 cells were used as an endogenous IL-10 producer. The NK sensitivity in vitro
      of W31T-H, a high IL-10-producer clone, was suppressed downward to the equivalent
      level of W31 cells pretreated with exogenous rhIL-10. The decreased NK
      sensitivity of W31T-H cells was further confirmed by in vivo Winn assay, in which
      nude mice challenged with W31T-H cells and rat NK cells together developed
      tumors, whereas nude mice challenged with W31T-L, a minimal-IL-10 producer clone,
      and NK cells did not. Since neither exogenous nor endogenous IL-10 affected the
      proliferation of W31 cells, the data indicated that W31T-H cells could evade the
      NK-cell-mediated immune response in vivo. Taken together, our data reveal a novel
      mechanism for an IL-10-mediated escape of tumor cells from host immune system by
      NK cells.

PMID- 9630839
TI  - Underproduction of interleukin-12 in susceptible mice during progressive
      leishmaniasis is due to decreased CD40 activity.
AB  - Interleukin-12 promotes Th1 lymphocyte responses necessary for the cure of murine
      Leishmania major infection. We found that IL-12 p40 mRNA expression peaked at 4
      weeks of infection in resistant C57BL/6 mice at levels threefold greater than in
      BALB/c mice. Peak IL-12 p40 expression in both strains was reduced threefold
      following treatment with neutralizing anti-CD40 ligand antibody and disease
      worsened in C57BL/6 mice. Direct activation of cultured lymph node cells by anti
      CD40 MAb or soluble CD40 ligand failed to restore deficient IL-12 production by
      infected BALB/c mice unless recombinant IFN-beta was added to culture. Infected
      BALB/c lymph nodes also contained two- to threefold fewer low-density CD40+
      accessory cells compared to that in C57BL/6 mice. We conclude that CD40-dependent
      responses are continually required for healing of leishmaniasis and that
      progressive disease is associated with decreased CD40-stimulated IL-12 synthesis
      as a consequence of either altered cytokine environment or inadequate accessory
      cell number.

PMID- 9630840
TI  - Endogenous activation of apoptosis in bursal lymphocytes: inhibition by phorbol
      esters and protein synthesis inhibitors.
AB  - The bursa of Fabricius represents the primary immune organ where immature B cells
      undergo maturational changes in avian species. Isolation of bursal lymphocytes
      for analysis in cell culture results in the rapid endogenous activation of
      apoptosis. After 2 h of incubation, over 45% of the lymphocytes were shown to be
      undergoing apoptosis and by 6 h 80% were undergoing apoptosis as demonstrated by
      a terminal deoxynucleotidyltransferase-mediated dUTP-fluorescein isothiocynate
      nick end-labeling flow-cytometric analysis. These results were corroborated by a
      propidium iodide-staining flow-cytometric assay and by an agarose gel
      electrophoresis DNA fragmentation assay that demonstrated internucleosomal DNA
      cleavage of genomic DNA in apoptotic bursal lymphocytes. Endogenous activation of
      apoptosis in bursal lymphocytes could be inhibited in a dose-dependent fashion
      with the phorbol ester, phorbol 12-myristate 13-acetate, but not the phorbol
      ester antagonist 4 alpha-phorbol 12,13-didecanoate. In addition, apoptosis could
      be inhibited in a dose-dependent fashion with inhibitors of protein translation,
      cycloheximide, and puromycin, as well as the transcriptional inhibitor
      actinomycin D. These results suggest that endogenous activation of bursal
      lymphocyte apoptosis may be mediated by the protein kinase C signal transduction
      pathway and activation of this process appears to be dependent upon de novo
      protein biosynthesis.

PMID- 9630841
TI  - Mouse alloantigen Ly10 is identical to murine fusion regulatory protein-1 (mFRP
      1)/4F2/CD98: aberrant expression of mFRP-1/Ly10 allotypes in cells derived from
      CDF1 mice due to the gene deletion.
AB  - Murine FRP-1 (mFRP-1) and Ly10 antigens are alloantigens. Anti-Ly10.1, monoclonal
      antibody (mAb) reacts to HeLa cells stably expressing mFRP-1.1 (HeLa cells/mFRP
      1.1), but does not react to HeLa cells/ mFRP-1.2. On the other hand, anti-Ly10.2
      mAb reacts to HeLa/mFRP-1.2 cells, but does not react to HeLa cells/mFRP-1.1.
      These findings indicate that Ly10.1 and Ly10.2 antigens are identical to the
      heavy chains of mFRP-1.1 and mFRP-1.2 molecules, respectively. Thymocytes and
      fibroblast cells obtained from CDF1 and BDF1 mice showed reactivity to both anti
      Ly10.1 and anti-Ly10.2/FRP-2 antibodies, indicating that mFRP-1/Ly10 alloantigens
      are codominantly expressed in the F1 mice. Intriguingly, IMC carcinoma cells,
      derived from CDF1 mice, express mFRP-1.2, but do not express mFRP-1.1.
      Surprisingly, DBT cells, derived from CDF1 mice, consist of two different cell
      populations: one expresses both mFRP-1.1 and mFRP-1.2 antigens and the other
      expresses only mFRP-1.1 antigen. Consequently, we tried to isolate cloned DBT
      cell lines by limiting dilution. Finally, six cloned DBT cell lines were
      obtained, and three clones of these cloned DBT cells expressed both mFRP-1.1 and
      mFRP-1.2, and another three clones of these cloned DBT cells expressed both mFRP
      1.1 and mFRP-1.2, and another three clones including clone 5 cells expressed only
      mFRP-1.1 antigen. No induction of mFRP-1.2/Ly10.2 by 5-azacytidine and sodium n
      butyrate could be detected in DBT clone 5 cells. Neither mFRP-1.2 mRNA nor the
      genomic cDNA clone encoding mFRP-1.2 could be detected in DBT clone 5 cells, nor
      could the genomic cDNA encoding mFRP-1.1 be detected in IMC cells, indicating
      that aberrant expression of mFRP-1/Ly10 allotypes in CDF1 mice-derived cells is
      due to the gene deletion.

PMID- 9630842
TI  - TL antigen is not linked to radioinduced thymic lymphoma.
AB  - X irradiation of C57BL/Ka mice induces thymic lymphoma after a period of 8 to 36
      weeks. This latency period represents an ideal time window in which to follow the
      development of prelymphoma cells that give rise to overt thymic lymphoma. Several
      attempts have been made to identify an unequivocal prelymphoma cell marker but
      these efforts have so far been unsuccessful. We monitored the evolution of
      thymocyte populations containing prelymphoma cells during the latency period,
      using CD3 and TL as markers, in a transfer assay. We demonstrated that: (1)
      particular cell populations could appear or disappear; (2) there were at least
      two prelymphoma phenotypes: CD3loTL+ and CD3hiTL-; (3) TL could be present
      transiently; and (4) TL could be absent throughout the latency period. We
      conclude that split-dose irradiation may induce both TL gene expression and a
      prelymphoma state but that the two are not necessarily related.

PMID- 9630843
TI  - Involvement of CYP3A1, 2B1, and 2E1 in C-8 hydroxylation and CYP 1A2 and flavin
      containing monooxygenase in N-demethylation of caffeine; identified by using
      inducer treated rat liver microsomes that are characterized with testosterone
      metabolic patterns.
AB  - Caffeine (CA) is oxidized by rat liver microsomal enzymes to theobromine (TB),
      paraxanthine (PX), and theophylline (TP) by N-demethylation and to trimethylurate
      (TMU) by C-8 hydroxylation, In order to identify the specific enzymes responsible
      for productions of these primary CA metabolites, liver microsomes enriched with
      various isoforms of cytochrome P450 (CYP) and flavin-containing monooxygenase
      (FMO) are prepared by pretreatment of rats with several inducers. The specific
      increases in various CYP or FMO activities are identified with the diagnostic
      testosterone metabolic patterns or the thiobenzamide S-oxidation assay. They are
      then employed to metabolize the CA. Liver microsomes isolated from rats
      pretreated with phenobarbital (PB-microsomes) did not have increased FMO activity
      but had increased activities for hydroxylating the testosterone at 6 beta
      (CYP3A1), 16 beta-(CYP2B1), and 2 beta-(CYP3A1) positions. This PB-microsomes had
      increased activity for TMU production from CA (result of C-8 hydroxylation).
      Liver microsomes isolated from rats pretreated with acetone (AC-microsomes) had a
      normal level of FMO activity but had enhanced rates of 6 beta-(CYP3A1) and 2 beta
      (CYP3A1) hydroxylations of testosterone. The AC-microsomes again had increased
      activity for production of TMU. Similarly, the liver microsomes isolated from
      rats pretreated with dexamethasone (DEX-microsomes) had a normal level of FMO
      activity but had enhanced rates of forming 6 beta-and 2 beta-hydroxytestosterone
      (Cyp3A1) as well as androstenedione (CYP3A1). The DEX-microsomes again had
      increased activity for production of TMU only. Liver microsomes isolated from
      rats pretreated with 3-methylcholanthrene (MC-microsomes), however, had increased
      FMO activity and also enhanced rates of forming the 7 alpha-(CYP1A1/2, and 2A1),
      6 beta-(CYP3A1), and 2 beta-(CYP3A1) hydroxytestosterone. The MC-microsomes had
      increased activity for producing all of the four primary metabolites of CA, i.e.
      the N-demethylation metabolites like TB, PX. and TP, as well as the C-8
      hydroxylation metabolite TMU. By the process of association of the obtained
      results, liver microsomes with increased contents of CYP2B1, 3A1, and 2E1 could
      catalyze the C-8 hydroxylation at an increased rate producing increased amount of
      TMU. Increased productions of CA N-demethylation metabolites (TB, PX, and TP)
      are, however, catalyzed by the increased activities of CYP1A2 and FMO which are
      associated uniquely with the MC-microsomes.

PMID- 9630844
TI  - Induction of a SOS repair system in lysogenic bacteria by zearalenone and its
      prevention by vitamin E.
AB  - Zearalenone (Zen) is an oestrogenic mycotoxin produced by several Fusarium
      species in cereals. It induces modifications of haematological parameters in rats
      with cytotoxicity and inhibition of macromolecular synthesis (nucleic acids and
      protein). Zen and its metabolites have oestrogenic and anabolic activities and
      interact with human oestrogen receptors. Zen and its metabolites showed a
      positive DNA damaging effect in recombination tests with Bacillus subtilis. It
      induces sister chromatid exchange and chromosomal aberration in CHO cells. Zen
      was found to be capable of inducing DNA-adduct formation in mouse liver. The
      genotoxicity of Zen was questionable until the last decade when increasing data
      tended to show this toxin to be genotoxic in vivo. However the mechanism of its
      genotoxicity and mutagenicity has not been completely clarified. The present
      investigations were designed to show whether Zen induces an SOS-DNA repair
      response in lysogenic bacteria which have an integrated lambda-bacteriophage in
      their genome. Zen was found to be genotoxic in the bacterial systems from a
      concentration of 1.50 mM and it was also bactericidal (IC50 = 1.45 mM). In
      addition vitamin E (6.0-12.0 mM) added 1 h prior to the toxin proved to prevent
      both the genotoxic and bactericidal effects of Zen. This vitamin could be active
      both as an antioxidant and as a radical scavenger. The specificity of this
      prevention is probably due to the similarity of structure between vitamin E and
      Zen.

PMID- 9630845
TI  - Age-dependent change of metabolic capacity and genotoxic injury in rat intestine.
AB  - The ontogeny of intestinal phase I and II xenobiotic metabolising enzymes and
      influence on susceptibility to genotoxic injury, are unclear. This study assessed
      expression of cytochrome P450 monooxygenases (CYP1A, CYP2B, CYP2C, CYP3A, CYP4A),
      glutathione-S-transferase (GSTA1/2, GSTA3, GSTA4, AND GSTM1), and uridine
      diphosphate glucuronosyl transferase (UGT) in rat intestine, between fetal life
      and maturity. Enzyme induction and DNA adduct formation were assessed after 3
      methylcholanthrene (MC) exposure. Untreated rat intestine expressed CYP2B,
      GSTA1/2, GSTA4 and UGT at all stages of maturation, although CYP2B and GSTA1/2
      increased in postnatal life. MC induced new expression of CYP1A, GSTA3 and
      enhanced expression of GSTA1/2 and UGT. Age-dependent differences of enzyme
      induction and DNA adduct formation between pre- and postnatal intestine and
      during postnatal maturation, were observed. Rat intestinal epithelium shows
      variable competence for MC metabolism and sustains disparate levels of DNA
      adducts during pre- and postnatal development.

PMID- 9630846
TI  - Covalent binding of carbamazepine reactive metabolites to P450 isoforms present
      in the skin.
AB  - Carbamazepine is an anticonvulsant associated with a high risk for severe
      cutaneous reactions. Upon metabolism by cytochrome P450, carbamazepine may
      produce reactive metabolites. We evaluated in vitro the covalent binding of
      carbamazepine reactive metabolites on human P450s and then the presence of these
      P450s in human epidermis. Carbamazepine reactive metabolites covalent binding to
      human liver microsomes involved P450 subfamilies 1A, 2C and 3A. Specific covalent
      binding to yeasts expressing different P450s showed that carbamazepine reactive
      metabolites bound specifically to P450 1A2 and 3A4. We confirmed the constitutive
      presence of P450 3A in human epidermis and after induction with coaltar of P450
      1A. Consequently, the production in epidermis of carbamazepine reactive
      metabolites is theoretically possible with formation of P450 adduct metabolites.

PMID- 9630847
TI  - Modification of cell cycle and viability of TLX5 lymphoma in vitro by sulfoxide
      ruthenium compounds and cisplatin detected by flow cytometry.
AB  - The effects of Na[trans-RuCl4(DMSO)Im] (NAMI), Na[trans-RuCl4(TMSO) Ind] (TIND)
      and Na[trans-RuCl4(TMSO)Iq] TEQU) were tested in vitro on TLX5 lymphoma cells in
      comparison to cisplatin by means of the sulforhodamine-B test SRB) for protein
      content determination, by acridine orange and propidium iodide staining and by
      means of the bromodeoxyuridine test, for cell cycle modifications. After 1 h drug
      exposure with metal-based drugs, TLX5 lymphoma cells require a further 72 h in
      vitro cultivation to show alteration of cell cycle. Ruthenium compounds show a
      different pattern of effects: TEQU causes the same dose-dependent cytotoxicity
      and DNA fragmentation shown by cisplatin, TIND reduces absorbance with the SRB
      test and slightly increases S and G2M populations with a time-dependent drug
      exposure of tumour cells, and NAMI is virtually devoid of any detectable effect.
      By in vivo bioassay of in vitro treated tumour cells, TIND and TEQU are effective
      independently of the time of drug exposure of tumour cells, this effect being
      confirmed by the same cell uptake of ruthenium after 1 or 4 h treatment,
      determined by atomic absorption spectroscopy. These data stress the lack of the
      involvement of direct cytotoxic effects in the potent anti-metastatic action of
      NAMI.

PMID- 9630848
TI  - A study on the antioxidant capacities of some benzimidazoles in rat tissues.
AB  - Seven benzimidazole compounds were synthesized and their in vitro effects on rat
      liver, lung and kidney microsomal NADPH-dependent lipid peroxidation (LP) levels
      were determined. The significant decrease in male rat liver microsomal LP level
      was noted only by the compound 4 at 10(-4) M (20%) and 10(-3) M (40%)
      concentrations whereas the other compounds were ineffective. In lung, only the
      compound 6 at 10(-4) M concentration exhibited significant alteration, i.e. 56%
      increase, in LP level. In kidney, however, apart from the compound 4, all the
      compounds increased LP level (35-52%) significantly. The classical antioxidant,
      butylated hydroxy toluene (BHT), at 10(-4) M concentration, significantly
      decreased LP level about 70%, in all the tissues studied. To clarify the effects
      of compounds 4 and 6 on LP, the responses of some CYPs, which are active in
      producing reactive oxygen species, to these compounds were also investigated. The
      compound 4 at 10(-4) and 10(-3) M concentrations inhibited the hepatic microsomal
      ethoxyresorufin O-deethylase (EROD) (37 and 65%) and pentoxyresorufin O
      depenthylase (PROD) (14 and 62%) enzyme activities significantly. However, it did
      not alter the hepatic microsomal NADPH-cytochrome P450-reductase activity. BHT,
      at 10(-3) M concentration, significantly inhibited hepatic microsomal EROD (73%),
      PROD (62%) and NADPH-cytochrome P450 reductase (17%) enzyme activities. Caffeine
      (10(-3)M) and SKF 525A (10(-3)M), which are specific inhibitors of EROD and PROD
      enzyme activities, significantly decreased the enzyme activities 33 and 77%,
      respectively. Caffeine was unable to alter hepatic microsomal NADPH-cytochrome
      P450 reductase enzyme activity whereas SKF 525A significantly inhibited (80%) it.
      In lung and kidney, the compound 6 at 10(-4)M concentration significantly
      increased EROD (44 and 19%) and PROD (103 and 86%) enzyme activities. However,
      the elevation of PROD enzyme activity in both tissues was observed to be more
      pronounced than that of EROD enzyme activity. This compound was ineffective on
      lung and kidney microsomal P450-reductase enzyme activity. These results reveal
      that the synthesized benzimidazoles have variable tissue dependent in vitro
      effects on LP due to their distinct effects on CYP activities but not on NADPH
      cytochrome P450 reductase activity in rats.

PMID- 9630849
TI  - The intestinal absorption of cadmium increases during a common viral infection
      (coxsackie virus B3) in mice.
AB  - Murine intestinal absorption, tissue accumulation and redistribution of 109Cd
      during infection were studied using the common human virus Coxsackie virus B3
      (CB3) adapted to the mouse. Female Balb/c mice were infected with CB3 and, on day
      4 of the infection, dosed orally with 0.3 or 750 microgram Cd/kg body weight,
      with 109Cd as a tracer, in order to study intestinal absorption and tissue
      distribution of Cd during infection (Experiment 1). Other mice were dosed with
      0.3 microgram Cd/kg body weight 3 days before being infected and, on day 4 of the
      infection, Cd redistribution was studied (Experiment 2). In both experiments non
      infected control animals received the same treatment as infected animals. Results
      showed that the infected animals had a higher gastrointestinal absorption of Cd
      than noninfected animals when Cd was administered during infection. In the
      infected animals the absorption at the low Cd dosage was increased by 70% and was
      tripled at the high dosage. The increased absorption enhanced the accumulation of
      Cd in all organs studied. Moreover, the infection caused a Cd dose-dependent
      change in the organ distribution of Cd, when Cd was administered during the
      infection. However, no redistribution of previously accumulated Cd occurred
      during ongoing disease, indicating that Cd was not mobilised from body stores by
      the infection. These results show, for the first time, that an invading micro
      organism can increase the intestinal absorption and concomitantly alter the
      tissue distribution of an environmental pollutant (Cd) if exposure occurs during
      the course of viral infection.

PMID- 9630850
TI  - Preservation versus section of intercostal-brachial nerve (IBN) in axillary
      dissection for breast cancer--a prospective randomized trial.
AB  - AIMS: Preservation of the intercostal-brachial nerve is advocated to reduce side
      effects of axillary dissection for breast cancer. We conducted a prospective
      randomized trail to compare functional results: sensory deficit and/or shoulder
      pain in preserved (group I) vs sacrificed (group II) intercostal-brachial nerve
      (IBN). METHODS: From July 1993 to April 1994, 128 patients presenting with an
      invasive operable breast cancer were operated on by mastectomy n = 28 or
      lumpectomy n = 100 and axillary dissection. The patients were eligible for
      randomization when the IBN was preserved at the end of the axillary dissection.
      Group I (nerve preservation) included 66 patients and group II (nerve section) 62
      patients. RESULTS: The two groups were well balanced for TNM, type of surgery,
      number of nodes dissected and positive, post-operative adjuvant treatment.
      Examinations were conducted at 3, 6 and 12 months after surgery. Sensory deficit
      in the IBN area was reported by one patient in group I and four patients in group
      II, at 3 months (P = 0.36, NS). No patients, apart from one in group II, reported
      functional trouble at 18 months. Major shoulder motion, limitation and pain
      developed in four patients in group I and three in group II (NS). This was
      attributed to depression and treated adequately. Analysis of sensory deficit was
      impossible in these patients. CONCLUSIONS: Conservation of the IBN, while
      anatomically preferable, is not functionally necessary during axillary dissection
      for breast cancer.

PMID- 9630851
TI  - Complications of latissimus dorsi myocutaneous flap breast reconstruction.
AB  - AIMS: To review the experience of a single unit in post-mastectomy reconstruction
      using the latissimus dorsi flap. METHODS: A retrospective review of 111 cases
      treated between 1984 and 1993. The notes were evaluated for type of procedure,
      associated treatment and complications. RESULTS: A significant morbidity of this
      procedure was demonstrated with 41 (37%) patients requiring a second operation
      during the period of the study. The majority of these second operations were
      related to the prosthesis used to achieve symmetry. Second operations were more
      common in those who had saline-filled prostheses. Other complications seen
      included wound infection, small areas of flap necrosis, hypertrophic scars and
      problems with the donor scar. No differences in complication rates were
      demonstrated for delayed vs immediate procedures or for patients receiving or not
      receiving radiotherapy. No life-threatening complication were seen during the
      study. CONCLUSIONS: The latissimus dorsi reconstruction is reliable but the
      overall programme is beset with considerable morbidity. This factor needs to be
      taken into consideration when discussing reconstructive options with the post
      mastectomy patient.

PMID- 9630853
TI  - Misidentification of an axillary sentinel lymph node due to anthracosis.

PMID- 9630852
TI  - Sentinel lymph node involvement--a predictor for axillary node status with breast
      cancer--has the time come?
AB  - AIMS: Axillary node dissection for breast cancer is important for staging and its
      prognostic value. Sentinel nodes are defined as the first nodes into which the
      primary cancer drains. This study investigates whether identification, removal
      and pathological examination of these nodes indicates whether the completion of
      axillary lymphadenectomy is required. METHODS: Using a vital dye injected at the
      primary tumour site, we were able to identify sentinel nodes in 96 out of 98
      women examined. RESULTS: An average number of 2.7 +/- 1.2 nodes per patient were
      identified as sentinel nodes. In 83% of cases there was a correlation between the
      involvement of the sentinel nodes and the rest of the axillary nodes. In 14% of
      patients the sentinel nodes were the only nodes involved with tumour. In three
      cases the sentinel nodes were negative, but other axillary nodes were tumour
      positive. CONCLUSION: The major problem in routine application of this method to
      the decision to perform axillary lymph node dissection (ALND) is the time needed
      for pathological identification of lymph node involvement by tumor.

PMID- 9630854
TI  - A histopathological assessment of the response of rectal adenocarcinoma to
      combination chemo-radiotherapy: relationship to apoptotic activity, p53 and bcl-2
      expression.
AB  - AIMS: To investigate the use of pre-operative chemo-irradiation in downstaging
      advanced rectal cancer prior to surgical resection. METHODS: We examined the
      pathological effects of chemo-irradiation on 24 rectal tumours and correlated the
      efficacy of treatment with the level of apoptosis, mitosis, P53 and bcl-2 protein
      expression on pre-treatment biopsies. RESULTS: All tumours were resectable
      following chemo-irradiation. Six cancers showed complete regression with no
      viable tumour in the resection specimen. A significant correlation was found
      between spontaneous tumour apoptosis and tumour regression. CONCLUSIONS: Our
      results suggest that in rectal cancer the apoptotic rate in untreated tumour
      tissue may predict sensitivity to radiation and cytotoxic agents. No relationship
      was found between regression and mitotic rate, p53 or bcl-2 expression.

PMID- 9630855
TI  - Resection of liver metastases from colorectal cancer: the real impact of the
      surgical margin.
AB  - AIMS: The benefit of liver resection for metastatic colorectal cancer is now
      established. Nevertheless if the surgical margin on pre-operative imaging is
      considered to be less than 10 mm, this is considered an absolute contraindication
      to surgery by some, and a relative contraindication by others, so its real impact
      on prognosis is not clear. METHODS: From 1984 to 1996, 269 patients underwent
      hepatectomy for liver metastases and were prospectively studied. The only two
      objectives of this surgery were to be curative (or achieve complete R0
      resection), and to avoid mortality. Of the 269, 187 patients had surgical margins
      inferior to 10 mm. Sixty per cent had multiple liver metastases, and 37% had
      extrahepatic metastatic sites. Their clinical and pathological factors were
      specifically studied. RESULTS: The crude 5-year survival of these 187 patients
      (including the 2% post-operative mortality) was 24.7%, and the disease-free
      survival was 18.8%. The surgical margin was 0 mm in 60 cases and was
      histologically invaded in 20 cases. The most important prognostic factor was
      whether the resection was considered palliative (R1-R2 resection according to
      UICC criteria) (P < 0.0001). When the cases with invaded margins were excluded,
      there was not prognostic difference between the 107 patients with a margin of 0-4
      mm and the 143 patients with a margin greater than 4 mm. However, a surgical
      margin greater than 9 mm appears to be a second prognostic factor (P = 0.001),
      when these 187 patients are compared to others. The reasons behind this are that
      there is a close relationship between narrow margins and extensive disease (high
      number of metastases, bilateral localization and extended hepatectomy), and also
      an increased possibility of microscopic satellite lesions within 10 mm around the
      metastases. CONCLUSION: The real prognostic impact of the surgical margin must
      not be overestimated. Hepatectomy for metastases can provide long-term survival
      in patients with supposed poor prognostic factors. Resection is justified so long
      as it is complete and with minimal risk. An experienced, specialized centre can
      be a prognostic determinant.

PMID- 9630856
TI  - Pre-operative evaluation of parotid tumours by fine needle biopsy.
AB  - AIMS: Although fine needle biopsy (FNB) is a well established diagnostic
      technique there continues to be controversy concerning its use in the pre
      operative assessment of intraparotid masses. The purpose of this study was to
      evaluate the diagnostic accuracy, specificity and sensitivity of FNB in parotid
      tumours and consequently to asses its clinical value. METHODS: Over a 6-year
      period, 129 consecutive patients with parotid masses underwent pre-operative FNB
      evaluation and in 121 of these cases the cytological diagnosis was confirmed.
      RESULTS: Out of the 86 cases cytologically diagnosed as benign, two false
      negative results were obtained by FNB, whereas out of the 38 cytological
      diagnoses of malignant tumours one case was found histologically to be Warthin's
      tumour. In the FNB results of the two cases suspicious for malignancy, one was
      confirmed histologically as malignant. Three cases of FNB with inadequate
      material were found to be benign lesions. In this trail, the diagnostic accuracy
      of FNB was 96.7%, the specificity, 97.6% and the sensitivity, 95%. CONCLUSIONS:
      Our results show that FNB is a valuable examination technique in the pre
      operative evaluation of parotid masses.

PMID- 9630857
TI  - Buttockectomy as a limbsaving procedure for locally advanced soft tissue sarcoma
      of the buttock region.
AB  - AIMS: To investigate the effectiveness of a buttockectomy, an unusual surgical
      procedure for locally advanced soft tissue sarcoma of the buttock region.
      METHODS: Nine buttockectomy procedures were performed in eight patients for
      primary (8) or recurrent (1) locally advanced soft tissue sarcoma of the
      buttocks. Adjuvant external beam radiation therapy was applied within 6 weeks
      after seven procedures. There were no post-operative complications. RESULTS: No
      local recurrences occurred in this series. However, distant metastases developed
      in five patients (63%) after a mean follow-up of 16 months (range 6-25). Overall
      and disease-free 5-year survival rates were 38 and 25% respectively. CONCLUSION:
      Buttockectomy with post-operative external beam radiation therapy may be an
      effective limbsaving treatment option to achieve local tumour control in selected
      soft tissue sarcomas of the buttock region without an increased surgical and/or
      radiation-induced morbidity.

PMID- 9630858
TI  - Breaking bad news.
AB  - The way in which news about a cancer diagnosis or recurrence is broken can have a
      profound effect on the patient's psychological wellbeing. When the information
      given is perceived by the patient as too much to too little and resultant
      concerns remain undisclosed and unresolved there is a high risk that the patient
      will develop clinical anxiety and/or depression. Guidelines are provided,
      therefore, to help them appropriately. Strategies are also suggested which will
      allow the patient's concerns to be elicited in an efficient but caring manner.

PMID- 9630859
TI  - Complications in connection with venous port systems: prevention and therapy.
AB  - Post-operative difficulties apart, venous thrombosis, extravasation and
      dislocation, obstruction, catheter leakage and local and systemic infections are
      the typical complications associated with venous port systems. Such complications
      considerably reduce the benefits otherwise accruing from a reliable access to the
      venous system of patients with malignant tumours. The vast majority of such
      disadvantages are attributable to the inexpert handling of ports and, therefore,
      should be avoidable. This applies to such areas as selecting the right port
      system, the proper installation of the port chamber and catheter and also to
      efficient handling and maintenance by trained staff. In may cases it will be
      possible, with the help of a specific diagnostic investigation, to identify and
      correct a fault and this ensure that the system installed continues to function.
      Typical and frequent complications observed (with specific examples) in
      connection with port systems are described together with preventative measures,
      diagnosis and therapy.

PMID- 9630860
TI  - Scytalols A, B, C, and D and other modulators of melanin biosynthesis from
      Scytalidium sp. 36-93.
AB  - From submerged cultures of Scytalidium sp. 36-93, ten metabolites were isolated
      due to their effects on dihydroxynaphthalene (DHN) or DOPA melanin biosynthesis.
      Four of the compounds, scytalols A (1a), B (1b), C (2) and D (3), are new
      secondary metabolites, the structures of which were determined by spectroscopy,
      while the other compounds are known. Scytalols A (1a) and D (3) are selective
      inhibitors of DHN melanin biosynthesis and exhibit no antifungal or cytotoxic
      activities. Nectriapyrone, 6-methoxymellein and 4-chloro-6-methoxymellein
      stimulated the formation of DOPA melanin in B16-F1 melanoma cells in the absence
      of melanin-stimulating hormone.

PMID- 9630861
TI  - Signal transduction inhibitors, hibarimicins, A, B, C, D and G produced by
      Microbispora. I. Taxonomy, fermentation, isolation and physico-chemical and
      biological properties.
AB  - Strain TP-AO121 which produces a complex of novel tyrosine kinase inhibitors
      designated hibarimicins A, B, C, D and G was considered to be a new subspecies of
      Microbispora rosea, and the name, Microbispora rosea subsp. hibaria, was
      proposed. Hibarimicins A, B, C and D specifically inhibited the src tyrosine
      kinase activity without affecting protein kinase A or protein kinase C. They also
      showed in vitro anti-Gram-positive bacterial and antitumor activities. The
      molecular formulae of hibarimicins A, B, C, D and G were assigned to be
      C85H112O37, C85H112O37, C83H110O36, C85H112O38, and C85H112O39 respectively.

PMID- 9630862
TI  - Signal transduction inhibitors, hibarimicins A, B, C, D and G produced by
      Microbispora. II. Structural studies.
AB  - The structure of hibarimicins A, B, C, D and G which are inhibitors for tyrosine
      specific protein kinase are determined using spectroscopic techniques.
      Hibarimicins described in this report consist of a common aglycon and six
      deoxyhexoses. The aglycon contains a highly oxidized naphtylnaphthoquinone as a
      chromophore. Among them, hibarimicin B was identical with angelmicin B.

PMID- 9630863
TI  - Isolation and structure of an antimitotic cyclic peptide, ustiloxin F: chemical
      interrelation with a homologous peptide, ustiloxin B.
AB  - Ustiloxin F, a microtubule inhibitor, was isolated as a minor metabolite of
      Ustilaginoidea virens. The structure was determined from the spectral data and by
      chemical interrelation to ustiloxin B through reductive removal of the sulfoxide
      containing side chain of ustiloxin B to give ustiloxin F. Ustiloxin F inhibited
      microtubule assembly with an IC50 value of 10.3 microM.

PMID- 9630864
TI  - Synthesis and anti-tubulin activity of ustiloxin D derivatives.
AB  - Ustiloxin D, produced by the rice plant pathogen Ustilaginoidea virens, exhibits
      potent anti-tubulin activity. In order to elucidate the effects of functional
      groups in ustiloxin D on its activity, several derivatives were synthesized and
      their anti-tubulin activities were estimated. The N,N-dimethylamino derivative
      and the 14-O-methyl derivative were inactive (IC50 > 50 microM). 20
      Hydroxymethylated ustiloxin D showed decreased inhibitory activity compared with
      ustiloxin D.

PMID- 9630865
TI  - Inhibitory activity to protein prenylation and antifungal activity of zaragozic
      acid D3, a potent inhibitor of squalene synthase produced by the fungus, Mollisia
      sp. SANK 10294.
AB  - Recently we found novel zaragozic acids (ZAs), F-10863A (zaragozic acid D3,
      ZAD3), B, C and D in the culture broth of the fungus Mollisia sp. SANK 10294 as
      potent inhibitors of squalene synthase. There are several other enzymes that use
      farnesylpyrophosphate as their substrate. Among them we chose farnesyl-protein
      transferase and examined whether ZAD3 and F-10863B inhibit this enzyme's
      activity. ZAD3 and F-10863B inhibited farnesyl-protein transferase with IC50
      values of 0.60 and 3.7 microM, respectively. They also inhibited geranylgeranyl
      protein transferase at similar concentrations. In addition, they exhibited potent
      antifungal activity.

PMID- 9630866
TI  - Cytotoxic metabolites produced by a fungal strain from a Sargassum alga.

PMID- 9630867
TI  - YM-170320, a novel lipopeptide antibiotic inducing morphological change of
      colonies in a mutant of Candida tropicalis pK233.

PMID- 9630868
TI  - Aranochlor A and aranochlor B, two new metabolites from Pseudoarachniotus roseus:
      production, isolation, structure elucidation and biological properties.

PMID- 9630869
TI  - NI15501A, a novel anthranilamide derivative from a marine fungus Penicillium sp.

PMID- 9630870
TI  - Terprenins, novel immunosuppressants produced by Aspergillus candidus.

PMID- 9630873
TI  - Noise, information, and the inverse square rule.

PMID- 9630871
TI  - Heme-dependent radical generation from antimalarial fungal metabolites, radicicol
      and heptelidic acid.

PMID- 9630874
TI  - The next step in managed health care?

PMID- 9630875
TI  - Therapeutic peptides: the devil is in the details.

PMID- 9630876
TI  - New drugs and changing disease paradigms.

PMID- 9630878
TI  - Bone morphogenetic proteins and tissue engineering.

PMID- 9630879
TI  - Lose fat now: ask me how.

PMID- 9630880
TI  - Progenics, Somatix in phase III cancer vaccine trials.

PMID- 9630881
TI  - Lighting up hybridization.

PMID- 9630882
TI  - Delivering biocontrol in the tropics.

PMID- 9630883
TI  - Binders from the deepest vaults.

PMID- 9630884
TI  - Dishing up clues to heart disease.

PMID- 9630885
TI  - Gene transfer to the mothers of all cells.

PMID- 9630886
TI  - Lymphokine racketeers? Cistron alleges foul play over IL-1, but Immunex sees it
      differently.

PMID- 9630887
TI  - G protein-coupled receptors and receptor kinases: from molecular biology to
      potential therapeutic applications.

PMID- 9630888
TI  - A benchside guide to patents and patenting.

PMID- 9630889
TI  - ICE/CED3-like proteases as therapeutic targets for the control of inappropriate
      apoptosis.
AB  - Excessive or failed apoptosis is a prominent morphological feature of several
      human diseases. Many of the key biochemical players that contribute to the highly
      ordered process of apoptotic cell death have recently been identified. These
      include members of the emerging family of cysteine proteases related to mammalian
      interleukin-1 beta converting enzyme (ICE) and to CED-3, the product of a gene
      that is necessary for programmed cell death in the nematode C. elegans. Among a
      growing number of potential molecular targets for the control of human diseases
      where inappropriate apoptosis is prominent, ICE/CED-3-like proteases may be an
      attractive and tangible point for therapeutic intervention.

PMID- 9630890
TI  - Molecular beacons: probes that fluoresce upon hybridization.
AB  - We have developed novel nucleic acid probes that recognize and report the
      presence of specific nucleic acids in homogeneous solutions. These probes undergo
      a spontaneous fluorogenic conformational change when they hybridize to their
      targets. Only perfectly complementary targets elicit this response, as
      hybridization does not occur when the target contains a mismatched nucleotide or
      a deletion. The probes are particularly suited for monitoring the synthesis of
      specific nucleic acids in real time. When used in nucleic acid amplification
      assays, gene detection is homogeneous and sensitive, and can be carried out in a
      sealed tube. When introduced into living cells, these probes should enable the
      origin, movement, and fate of specific mRNAs to be traced.

PMID- 9630891
TI  - Human antibodies with sub-nanomolar affinities isolated from a large non
      immunized phage display library.
AB  - To generate a stable resource from which high affinity human antibodies to any
      given antigen can be rapidly isolated, functional V-gene segments from 43 non
      immunized human donors were used to construct a repertoire of 1.4 x 10(10) single
      chain Fv (scFv) fragments displayed on the surface of phage. Fragments were
      cloned in a phagemid vector, enabling both phage displayed and soluble scFv to be
      produced without subcloning. A hexahistidine tag has been incorporated to allow
      rapid purification of scFv by nickel chelate chromatography. This library format
      reduces the time needed to isolate monoclonal antibody fragments to under two
      weeks. All of the measured binding affinities show a Kd < 10 nM and off-rates of
      10(-3) to 10(-4) s-1, properties usually associated with antibodies from a
      secondary immune response. The best of these scFvs, an anti-fluorescein antibody
      (0.3 nM) and an antibody directed against the hapten DTPA (0.8 nM), are the first
      antibodies with subnanomolar binding affinities to be isolated from a naive
      library. Antibodies to doxorubicin, which is both immunosuppressive and toxic, as
      well as a high affinity and high specificity antibody to the steroid hormone
      oestradiol have been isolated. This work shows that conventional hybridoma
      technology may be superseded by large phage libraries that are proving to be a
      stable and reliable source of specific, high affinity human monoclonal
      antibodies.

PMID- 9630893
TI  - Metabolism of nitrate esters by a consortium of two bacteria.
AB  - The products of condensation of organic alcohols and nitric acid are nitrate
      esters with the general structure C-O-NO2. These products are widely employed as
      vasodilators and explosives, and are true xenobiotic compounds, as they do not
      occur in nature. We have isolated and characterized a consortium of two
      microorganisms, Arthrobacter ilicis and Agrobacterium radiobacter, that
      mineralized recalcitrant ethylene glycol dinitrate. The Arthrobacter strain was
      the actual degrading microorganism, although the second microbe facilitated
      mineralization. The biodegradation of ethylene glycol dinitrate by A. ilicis
      involved the progressive elimination of the nitro groups from the organic
      molecule to generate ethylene glycol, which was then mineralized. Waters polluted
      with ethylene glycol dinitrate have been shown amenable to biological treatment
      in a pilot plant with wastewaters generated during the synthesis of the chemical
      in a factory.

PMID- 9630892
TI  - Improved green fluorescent protein by molecular evolution using DNA shuffling.
AB  - Green fluorescent protein (GFP) has rapidly become a widely used reporter of gene
      regulation. However, for many organisms, particularly eukaryotes, a stronger
      whole cell fluorescence signal is desirable. We constructed a synthetic GFP gene
      with improved codon usage and performed recursive cycles of DNA shuffling
      followed by screening for the brightest E. coli colonies. A visual screen using
      UV light, rather than FACS selection, was used to avoid red-shifting the
      excitation maximum. After 3 cycles of DNA shuffling, a mutant was obtained with a
      whole cell fluorescence signal that was 45-fold greater than a standard, the
      commercially available Clontech plasmid pGFP. The expression level in E. coli was
      unaltered at about 75% of total protein. The emission and excitation maxima were
      also unchanged. Whereas in E. coli most of the wildtype GFP ends up in inclusion
      bodies, unable to activate its chromophore, most of the mutant protein is soluble
      and active. Three amino acid mutations appear to guide the mutant protein into
      the native folding pathway rather than toward aggregation. Expressed in Chinese
      Hamster Ovary (CHO) cells, this shuffled GFP mutant showed a 42-fold improvement
      over wildtype GFP sequence, and is easily detected with UV light in a wide range
      of assays. The results demonstrate how molecular evolution can solve a complex
      practical problem without needing to first identify which process is limiting.
      DNA shuffling can be combined with screening of a moderate number of mutants. We
      envision that the combination of DNA shuffling and high throughput screening will
      be a powerful tool for the optimization of many commercially important enzymes
      for which selections do not exist.

PMID- 9630894
TI  - ABGEN: a knowledge-based automated approach for antibody structure modeling.
AB  - Immunoglobulin (Ig) amino acid sequences are highly conserved and often have
      sequence homology ranging from 70 to 95%. Antigen binding fragments (Fab),
      variable region fragments (Fv), and single chain Fv (scFv) of more than 50
      myeloma proteins and monoclonal antibodies (mAb) have been crystallized and
      display a high degree of structural similarity. Based on this observation,
      several homology modeling approaches have been developed for the prediction of
      Fab and Fv structures prior to their experimental determination. We have
      extracted features from existing Ig sequences, 44 known Fab and Fv structures to
      create an automated AntiBody structure GENeration (ABGEN) algorithm for obtaining
      structural models of antibody fragments. ABGEN utilizes a homology based
      scaffolding technique, and includes the use of invariant and strictly conserved
      residues, structural motifs of known Fab, canonical features of hypervariable
      loops, torsional constraints for residue replacements and key inter-residue
      interactions. The validity of the ABGEN algorithm has been tested using a five
      fold cross validation with the existing Fab structures. Molecular mechanics and
      dynamics methods have been implemented with ABGEN models to accurately predict
      two Fab structures of anti-sweetener antibodies prior to crystallographic
      determinations.

PMID- 9630895
TI  - Improved refolding of an immobilized fusion protein.
AB  - Fusion proteins of monomeric alpha-glucosidase from Saccharomyces cerevisiae
      containing N- or C-terminal hexa-arginie peptides were expressed in the cytosol
      of Escherichia coli in soluble form. The polycationic peptide moieties allow
      noncovalent binding of the denatured fusion proteins to a polyanionic solid
      support. Upon removal of the denaturant, refolding of the matrix-bound protein
      can proceed without perturbation by aggregation. However, nonspecific
      interactions of the denatured polypeptide, or of folding intermediates, with the
      matrix cause a drastic decrease in renaturation under suboptimal folding
      conditions. At low salt concentrations, ionic interactions of the refolding
      polypeptide with the matrix result in lower yields of renaturation. At higher
      salt concentrations, renaturation is prevented by hydrophobic interactions with
      the matrix. Apart from ionic strength, renaturation of the denatured matrix-bound
      fusion protein must be optimized with respect to pH, temperature, cosolvents, and
      matrix material used. Under optimum conditions, immobilized alpha-glucosidase can
      be renatured with a high yield at protein concentrations up to 5 mg/ml, whereas
      folding of the wild-type enzyme in solution is feasible only at an extremely low
      protein concentration (15 micrograms/ml). Thus, folding of the immobilized alpha
      glucosidase allows an extremely high yield of the renaturated model protein. The
      technology should be applicable to other proteins that tend to aggregate during
      refolding.

PMID- 9630896
TI  - Engineered biosynthesis of novel polyketides: properties of the whiE
      aromatase/cyclase.
AB  - The ORFVI from the cluster of genes, which is responsible for the biosynthesis of
      the Streptomyces coelicolor spore pigment, the whiE cluster, has been described
      as a bifunctional aromatase/cyclase. In order to evaluate its potential use for
      generating novel polyketides, combinations of this gene with those encoding
      minimal polyketide synthase enzymes with or without a ketoreductase from S.
      coelicolor A3(2) were constructed and analyzed in vivo. Analysis of the
      polyketide products generated from these constructs indicates that the whiE-ORFVI
      enzyme has properties similar to those of TcmN, although the whiE
      aromatase/cyclase normally acts on a polyketide intermediate that is four carbons
      longer than the TcmN substrate. The whiE aromatase/cyclase can influence the
      regiospecificity of the first cyclization of unreduced, but not reduced,
      backbones and is also responsible for the second ring aromatization. An unusual
      new polyketide, EM18, was identified which is not seen in equivalent strains
      expressing the tcmN aromatase/cyclase or the act aromatase genes. The structure
      of EM18 suggests that the WhiE-ORFVI product might have some unique properties
      within this family of polyketide synthase subunits, and may therefore be useful
      in the design of combinatorial biosynthetic strategies.

PMID- 9630897
TI  - Virosomes: cationic liposomes enhance retroviral transduction.
AB  - Retrovirus-derived vectors are overwhelmingly preferred over other methods for ex
      vivo gene therapy because they provide permanent integration of foreign genes
      into cellular DNA. In comparison, cationic lipids mediate efficent gene transfer,
      but expression is transient. When we combined cationic lipids with retrovirus
      particles we obtained a significant enhancement of transduction efficiency,
      depending upon the type of lipid formulation and the dose used. The relative
      effectiveness of these cytofectins was: DOSPA:DOPE > DOTMA:DOPE > DOTAP,
      resulting in 60-, 37-, and 5-fold increases in transduction efficiency,
      respectively, at optimum dosage. The effect of polycationic DOSPA:DOPE was
      dependent upon the viral envelope glycoprotein, was attainable by lipid treatment
      of either cells or virus particles, was not enhanced by the addition of
      polybrene, and was inhibited by chloroquine. These results strongly suggested
      that DOSPA:DOPE act primarily by modulation of charge associated with the viral
      envelope and cell membrane, enhancing retroviral transduction, rather than by
      providing an alternative pathway of transfection. DOSPA:DOPE is useful for
      improving the efficiency of gene transfer as well as the sensitivity with which
      retroviruses can be detected in biological fluids.

PMID- 9630898
TI  - Efficient synthesis of mosquitocidal toxins in Asticcacaulis excentricus
      demonstrates potential of gram-negative bacteria in mosquito control.
AB  - The control of mosquitoes with chemical insecticides pollutes the environment and
      leads to resistance in mosquito populations. Bacterial control of mosquito larvae
      with Bacillus sphaericus and Bacillus thuringiensis subsp. israelensis, which
      produce protein toxins, has proved useful, safe, and nonpolluting. These bacteria
      do, however, suffer from disadvantages, including rapid setting, UV sensitivity,
      and lack of persistance of spores, proteolysis of toxins, narrow host range, and
      high production costs. Here we show that the Gram-negative bacterium
      Asticcacaulis excentricus is a promising host for delivering toxins to mosquito
      larvae. Plasmid-transformed A. excentricus cells expressing the binary toxin of
      B. sphaericus exhibited toxicity to Culex and Anopheles mosquito larvae similar
      to that of the high-toxicity strains of B. sphaericus which produce several
      toxins. A. excentricus has potential advantages as a larvicide compared with the
      bacilli, especially persistance in the larval feeding zone, resistance to UV
      light, lack of toxin-degrading proteases, and low production costs.

PMID- 9630899
TI  - Detection of low affinity interactions between peptides and heat shock proteins
      by chemiluminescence of enhanced avidity reactions (CLEAR).
AB  - Protein-protein and protein-peptide interactions that are low affinity in nature
      preclude the straightforward measurement of binding. To overcome this limitation,
      a novel method has been devised for stabilizing these weak interactions by
      increasing the binding avidity. These studies have focused on the binding of
      peptides to heat shock proteins (with a typical KD of approximately 25 to 50
      microM). Multivalent ligands have been created by coupling peptides plus biotin
      to a neutral carrier molecule, dextran. These peptide-dextran conjugates allow
      for more avid binding to proteins that have been immobilized on a membrane
      surface. Detection of signals via enhanced chemiluminescence further increases
      the sensitivity of the method that has been termed Chemiluminescence of Enhanced
      Avidity Reactions (CLEAR). The assay is simple, reliable and consistently detects
      specific binding between heat shock proteins and peptide ligands. CLEAR should be
      generally applicable to other ligand receptor pairs where the detection of
      binding is limited by the low affinity of the interaction.

PMID- 9630900
TI  - Will the real inventor please stand up?

PMID- 9630901
TI  - Live-cell microscopy: environmental control for mammalian specimens.

PMID- 9630903
TI  - Shopping for biotechnology products on the Web: a user's guide.

PMID- 9630902
TI  - DNA shuffling brightens prospects for GFP.

PMID- 9630904
TI  - FDA drug approvals: no worse is simply not good enough.

PMID- 9630905
TI  - Xenotransplantation and the "yuk" factor.

PMID- 9630906
TI  - European field trials with transgenic plants.

PMID- 9630907
TI  - Parascientific education for PhDs.

PMID- 9630908
TI  - Bad blood settlement in Japan.

PMID- 9630909
TI  - Stents and biology combination for restenosis.

PMID- 9630910
TI  - Xenotransplantation: proceed with caution.

PMID- 9630911
TI  - Beyond protease inhibitors.

PMID- 9630912
TI  - Diabetes treatments near and far.

PMID- 9630913
TI  - Visualizing virus fitness gains.

PMID- 9630914
TI  - Is random mutation more rational?

PMID- 9630915
TI  - Unexpected pathways to protein stabilization.

PMID- 9630916
TI  - Slow release devices: STD protection at last?

PMID- 9630917
TI  - Industry and the university.

PMID- 9630918
TI  - Genetic engineering to enhance microbial interference and related therapeutic
      applications.

PMID- 9630919
TI  - Electrospray ionization and matrix assisted laser desorption/ionization mass
      spectrometry: powerful analytical tools in recombinant protein chemistry.
AB  - Electrospray ionization and matrix assisted laser desorption/ionization are
      effective ionization methods for mass spectrometry of biomolecules. Here we
      describe the capabilities of these methods for peptide and protein
      characterization in biotechnology. An integrated analytical strategy is presented
      encompassing protein characterization prior to and after cloning of the
      corresponding gene.

PMID- 9630920
TI  - Directed evolution of a para-nitrobenzyl esterase for aqueous-organic solvents.
AB  - Through sequential generations of random mutagenesis and screening, we have
      directed the evolution of an esterase for deprotection of an antibiotic p
      nitrobenzyl ester in aqueous-organic solvents. Because rapid screening directly
      on the desired antibiotic (loracarbef) nucleus p-nitrobenzyl ester was not
      feasible, the p-nitrophenyl ester was employed. Catalytic performance on the
      screening substrate was shown to reasonably mimic enzyme activity toward the
      desired ester. One p-nitrobenzyl esterase variant performs as well in 30%
      dimethylformamide as the wildtype enzyme in water, reflecting a 16-fold increase
      in esterase activity. Random pairwise gene recombination of two positive variants
      led to a further two-fold improvement in activity. Considering also the increased
      expression level achieved during these experiments, the net result of four
      sequential generations of random mutagenesis and the one recombination step is a
      50-60-fold increase in total activity. Although the contributions of individual
      effective amino acid substitutions to enhanced activity are small (< 2-fold
      increases), the accumulation of multiple mutations by directed evolution allows
      significant improvement of the biocatalyst for reactions on substrates and under
      conditions not already optimized in nature. The positions of the effective amino
      acid substitutions have been identified in a pNB esterase structural model
      developed based on its homology to acetylcholinesterase and triacylglycerol
      lipase. None appear to interact directly with the antibiotic substrate, further
      underscoring the difficulty of predicting their effects in a 'rational' design
      effort.

PMID- 9630921
TI  - Controlled release of antibodies for long-term topical passive immunoprotection
      of female mice against genital herpes.
AB  - Current methods for sexually transmitted diseases (STD) prophylaxis, which can be
      disruptive and inconvenient, must be used before each act of sexual intercourse,
      so a method that provides protection over the course of many acts is desirable.
      We used a mouse model of vaginally-transmitted herpes simplex virus 2 (HSV-2)
      infection to test polymeric controlled-release devices for sustained passive
      immunoprotection. Vaginal disks were prepared by dispersing a monoclonal antibody
      to HSV-2 (III-174) within a matrix of poly(ethylene-co-vinyl acetate); these
      disks released 2 to 40 micrograms/day of antibody into buffered water. When disks
      were placed in the vagina, large amounts of III-174 (5 to 3,000 ng) were
      recovered from the vaginal fluid over the next 8 days. Mice were vaginally
      challenged with 10 ID50 of HSV-2 either 3 or 7 days after disk placement; no mice
      receiving III-174 disks became infected, while 65% of control mice receiving
      identical disks with nonspecific IgG did. Controlled-release disks with III-174
      provided significant protection against HSV-2 infection (p < 0.005). This new
      technology for long-term STD prophylaxis should increase user compliance, a
      factor limiting the efficacy of current methods.

PMID- 9630922
TI  - Synthetic CD4 exocyclic peptides antagonize CD4 holoreceptor binding and T cell
      activation.
AB  - We have developed peptide analogs to analyze precise human CD4 substructures
      involved in MHC class II binding. Forms of the complementarity determining-like
      regions (CDRs) of the D1 domain of human CD4 were reproduced as synthetic
      aromatically modified exocyclic (AME) analogs and tested for their ability to
      block CD4-MHC II interactions and T cell activation. The exocyclic derived from
      CDR3 (residues 82-89) of human CD4, which specifically associated with CD4 on the
      T cell surface to create a heteromeric CD4 complex, blocked IL-2 production and
      antagonized the normal function of the CD4 receptor. The approach of creating
      novel synthetic antagonistic receptor complexes may represent a new receptor
      specific pharmaceutical approach to modulate biological function.

PMID- 9630924
TI  - A fusion protein designed for noncovalent immobilization: stability, enzymatic
      activity, and use in an enzyme reactor.
AB  - We have designed a new method for enzyme immobilization using a fusion protein of
      yeast alpha-glucosidase containing at its C-terminus a polycationic hexa-arginine
      fusion peptide. This fusion protein can be directly adsorbed from crude cell
      extracts on polyanionic matrices in a specific, oriented fashion. Upon
      noncovalent immobilization by polyionic interactions, the stability of the fusion
      protein is not affected by pH-, urea-, or thermal-denaturation. Furthermore, the
      enzymatic properties (specific activity at increasing enzyme concentration,
      Michaelis constant, or activation energy of the enzymatic reaction) are not
      influenced by this noncovalent coupling. The operational stability of the coupled
      enzyme under conditions of continuous substrate conversion is, however, increased
      significantly compared to the soluble form. Fusion proteins containing polyionic
      peptide sequences are proposed as versatile tools for the production of
      immobilized enzyme catalysts.

PMID- 9630923
TI  - Effect of disulfide bonds on the structure, function, and stability of the
      trypsin/tPA inhibitor from Erythrina caffra: site-directed mutagenesis,
      expression, and physiochemical characterization.
AB  - Erythrina trypsin/tPA inhibitor (ETI) from the seeds of Erythrina caffra retains
      its native structure and inhibitory function after reducing its two disulfide
      bonds. In order to elucidate the specific role of these crosslinks, alanine
      residues were substituted for cysteines after cloning the gene in Escherichia
      coli. Expression of the recombinant inhibitor and the substitution mutants, C83A,
      CC39, 83AA, and CC132, 139AA, led to inclusion bodies. After solubilization in
      guanidinium-chloride (GdmCl)/dithiothreitol and oxidation in glutathione buffer,
      activity could be recovered at yields up to 80%. The mutant proteins exhibit full
      inhibitory function without detectable alterations of their native structure.
      However, their stability is reduced: at acid pH, where the oxidized natural
      inhibitor retains its native structure, the reduced wildtype protein and the
      mutants undergo at least partial denaturation, reflected by decreased pH ranges
      of stability: pH 5-7 for the reduced inhibitor, pH 2.5-8.5 for CC132, 139AA, and
      pH 3.5-8.5 for C83A and CC39, 83AA. Urea and GdmCl denaturation at pH 7 show
      hysteresis for both the oxidized inhibitor and the double mutant CC132, 139AA. In
      contrast, the reduced protein and the other mutants exhibit true equilibrium
      transitions at pH 7, with urea half-concentrations of 0.9 M and 1.9 M and GdmCl
      half-concentrations of 0.5 M and 1.0 M, respectively. The stability of Erythrina
      trypsin/tPA inhibitor follows the sequence: oxidized ETI > CC132, 139AA > CC39,
      83AA and C83A > reduced ETI.

PMID- 9630925
TI  - Radioactive labeling of recombinant antibody fragments by phosphorylation using
      human casein kinase II and [gamma-32P]-ATP.
AB  - A wide range of antibody fragments can be expressed in bacteria and detected
      immunochemically via peptide tags. Using specially designed tags, we have
      developed a strategy for radiolabeling antibody fragments secreted from bacteria.
      Tagged antibody fragments were secreted either into the bacterial periplasm or
      the culture medium. The tag was not subject to proteolysis either in the broth or
      in human plasma. After affinity purification the antibody fragments were
      phosphorylated with [gamma-32P]ATP and casein kinase II. The labeled fragments
      were used in a gel band-shift assay to measure antigen binding affinities. In
      contrast to non site-specific methods such as radioiodination, antibodies labeled
      with casein kinase II retain full immunoreactivity. Radioactively phosphorylated
      antibody fragments may have many other applications, including radioimmunoassays
      and radioimmunotherapy.

PMID- 9630926
TI  - Detection of evolving viruses.
AB  - The spread of viruses on a homogeneous lawn of receptive hosts provides an
      opportunity to detect the dynamics of their evolution. We have previously found
      that when repeated virus passages are confined to the expanding perimeter of a
      growing plaque, the appearance and outgrowth of genetically diverse strains (all
      descended from the same parent strain) can be traced along different radii of the
      plaque. As a plaque grows, the random mutation and selection of new fast-growing
      strains reduce the roundness or circularity of the growing plaque. Here we have
      quantified such changes in growing plaques of bacteriophage T7 using a digital
      imaging system. We find that T7 populations not adapted for fast growth exhibit a
      broader diversity of growth rates than populations adapted for fast growth. These
      results provide a foundation for understanding how viruses exploit mutation and
      selection processes to persist in nature.

PMID- 9630927
TI  - Transgenic rice plants harboring an introduced potato proteinase inhibitor II
      gene are insect resistant.
AB  - We introduced the potato proteinase inhibitor II (PINII) gene (pin2) into several
      Japonica rice varieties, and regenerated a large number of transgenic rice
      plants. Wound-inducible expression of the pin2 gene driven by its own promoter,
      together with the first intron of the rice actin 1 gene (act1), resulted in high
      level accumulation of the PINII protein in the transgenic plants. The introduced
      pin2 gene was stably inherited in the second, third, and fourth generations, as
      shown by molecular analyses. Based on data from the molecular analyses, several
      homozygous transgenic lines were obtained. Bioassay for insect resistance with
      the fifth-generation transgenic rice plants showed that transgenic rice plants
      had increased resistance to a major rice insect pest, pink stem borer (Sesamia
      inferens). Thus, introduction of an insecticidal proteinase inhibitor gene into
      cereal plants can be used as a general strategy for control of insect pests.

PMID- 9630928
TI  - Efficient control of gene expression by single step integration of the
      tetracycline system in transgenic mice.
AB  - Tetracycline-regulated gene expression in eukaryotic cell lines, plants, and
      transgenic mice has become a powerful tool for the analysis of eukaryotic gene
      expression and function. The system consists of two plasmids, one encoding the
      transactivator protein under control of a viral cytomegalovirus promoter, and the
      second being the tet-operator minimal promoter driving the gene of interest. Here
      we show that these control elements, when integrated in cis on a single plasmid,
      allow efficient and tight control of reporter gene expression in vitro and in
      vivo. Dependent on the route of administration of tetracycline, gene expression
      can be partially or fully repressed in transgenic mice, whereas removal of the
      antibiotic induces the reporter gene in various tissues to levels up to 800-fold
      more than the two-plasmid system. In addition, crossing and analysis of animals
      transgenic for the individual components of the system are unnecessary, and
      genetic segregation of the control elements during breeding is prevented.

PMID- 9630929
TI  - Affinity-based screening of combinatorial libraries using automated, serial
      column chromatography.
AB  - We have developed an automated serial chromatographic technique for screening a
      library of compounds based upon their relative affinity for a target molecule. A
      "target" column containing the immobilized target molecule is set in tandem with
      a reversed-phase column. A combinatorial peptide library is injected onto the
      target column. The target-bound peptides are eluted from the first column and
      transferred automatically to the reversed-phase column. The target-specific
      peptide peaks from the reversed-phase column are identified and sequenced. Using
      a monoclonal antibody (3E-7) against beta-endorphin as a target, we selected a
      single peptide with sequence YGGFL from approximately 5800 peptides present in a
      combinatorial library. We demonstrated the applicability of the technology
      towards selection of peptides with predetermined affinity for bacterial
      lipopolysaccharide (LPS, endotoxin). We expect that this technology will have
      broad applications for high throughout screening of chemical libraries or natural
      product extracts.

PMID- 9630930
TI  - Experimental use and the Orphan Drug Act: a biotechnology conundrum.

PMID- 9630932
TI  - Thermocycling on the Web: a user's guide.

PMID- 9630931
TI  - High throughput screening on a low budget.

PMID- 9630934
TI  - Genomics moves out of research.

PMID- 9630933
TI  - Legislative insurance against genetic discrimination is insurance for
      biotechnology.

PMID- 9630936
TI  - Two bright new faces in gene therapy.

PMID- 9630935
TI  - US herd instinct: no mad cows here.

PMID- 9630937
TI  - Surreal US budget again favors R&D spending.

PMID- 9630938
TI  - Yeast: a sequence model, not a management one.

PMID- 9630939
TI  - Genzyme's Seprafilm gets FDA marketing nod.

PMID- 9630940
TI  - Research answers critics of bionic knee technique.

PMID- 9630941
TI  - "Green light" for gene transfer.

PMID- 9630942
TI  - Finally, some signaling molecules find a home in yeast.

PMID- 9630943
TI  - A new target for gene therapeutics: telomerase.

PMID- 9630944
TI  - Breaking through gridlock on the aromatic thruway (to lower-cost specialty
      chemicals)

PMID- 9630945
TI  - Grape expectations realized.

PMID- 9630946
TI  - Exploring and exploiting the antibody and Ig superfamily combining sites.

PMID- 9630947
TI  - Using host defenses to fight infectious diseases.

PMID- 9630948
TI  - Vaccine R&D success rates and development times.

PMID- 9630949
TI  - Locating and characterizing binding sites on proteins.
AB  - This review article begins with a discussion of fundamental differences between
      substrates and inhibitors, and some of the assumptions and goals underlying the
      design of a new ligand to a target protein. An overview is given of the methods
      currently used to locate and characterize ligand binding sites on protein
      surfaces, with focus on a novel approach: multiple solvent crystal structures
      (MSCS). In this method, the X-ray crystal structure of the target protein is
      solved in a variety of organic solvents. Each type of solvent molecule serves as
      a probe for complementary binding sites on the protein. The probe distribution on
      the protein surface allows the location of binding sites and the characterization
      of the potential ligand interactions within these sites. General aspects of the
      application of the MSCS method to porcine pancreatic elastase is discussed, and
      comparison of the results with those from X-ray crystal structures of
      elastase/inhibitor complexes is used to illustrate the potential of the method in
      aiding the process of rational drug design.

PMID- 9630950
TI  - A functional screen in yeast for regulators and antagonizers of heterologous
      protein tyrosine kinases.
AB  - Tyrosine phosphorylation exerts a pivotal role in cell regulation processes of
      higher eukaryotes. Tight control of the activity of protein tyrosine kinases is
      crucial for ordered phosphorylation to occur. We have developed a functional
      screen for tyrosine kinase regulators using c-Src, the first cellular protein
      tyrosine kinase described, as a prototype; and fission yeast, Schizosaccharomyces
      pombe, as a genetically amenable host system. Inducible expression of c-Src in
      fission yeast is lethal. We have screened human cDNA libraries for clones able to
      counteract the lethal effect of Src. Two different classes of cDNAs, which we
      called SAS for sequences antagonizing Src, were obtained. The first class encodes
      for the protein tyrosine kinase Csk, known to regulate Src activity through
      phosphorylation of the C-terminal tyrosine. The second class consists of clones
      encoding three different tyrosine phosphatases, counteracting Src action by
      dephosphorylation of Src substrates and by dephosphorylation of Src itself. The
      system described here can be applied to identify regulators of other heterologous
      tyrosine kinases, including receptor-type tyrosine kinases, which impair growth
      of S. pombe.

PMID- 9630951
TI  - Use of green fluorescent protein variants to monitor gene transfer and expression
      in mammalian cells.
AB  - Two mutants of the green fluorescent protein (GFP), RSGFP4 and GFPS65T, have been
      recently created which differ from the wildtype GFP of A. victoria in their
      excitation maxima. Here we show that human fibroblasts transfected with either of
      the two mutant GFP genes emit a green fluorescence that is 18-fold brighter than
      the cells transfected with the wildtype GFP gene. Retroviral vectors expressing
      the improved GFP gene were also constructed to determine their suitability for
      stable gene transduction into mammalian cells. The inclusion of the RSGFP4 gene
      in a retroviral vector did not reduce the viral titer and resulted in a
      fluorescent signal in viable transduced cells detectable by both fluorescence
      microscopy and fluorescence-activated cell sorter (FACS) analysis. Therefore, the
      improved mutant GFP provides a vital marker for monitoring gene transfer and
      expression in mammalian cells.

PMID- 9630952
TI  - Retroviral transfer and expression of a humanized, red-shifted green fluorescent
      protein gene into human tumor cells.
AB  - Over two-thirds of the current gene therapy protocols use retroviral gene
      transfer systems. We have developed an efficient retroviral-based method that
      allows rapid identification of gene transfer in living mammalian cells. Cells
      were generated containing a gene for an improved (humanized, red-shifted) version
      of the Aequorea victoria green fluorescent protein (hRGFP) from a retroviral
      vector. The hRGFP gene was used to produce an amphotropic vector producer cell
      line that demonstrated vibrant green fluorescence after excitation with blue
      light. A375 melanoma cells transduced with the retroviral vector demonstrated
      stable green fluorescence. Both PA317 murine fibroblasts and A375 human cell
      lines containing the vector were easily detected by FACS analysis. These vectors
      represent a substantial improvement over currently available gene transfer
      marking systems. Bright, long-term expression of the hRGFP gene in living
      eukaryotic cells will advance the study of gene transfer, gene expression, and
      gene product function in vitro and in vivo particularly for human gene therapy
      applications.

PMID- 9630953
TI  - Inhibition of human telomerase activity by peptide nucleic acids.
AB  - We report the inhibition of human telomerase activity by peptide nucleic acids
      (PNAs). PNAs recognize the RNA component of human telomerase (hTR) and inhibit
      activity of the enzyme with IC50 values in the picomolar to nanomolar range.
      Inhibition depends on targeting exact functional boundaries of the hTR template
      and is 10- to 50-fold more efficient than inhibition by analogous
      phosphorothioate (PS) oligomers. In contrast to high selectivity of inhibition by
      PNAs, PS oligomers inhibit telomerase in a non-sequence-selective fashion. These
      results demonstrate that PNAs can control the enzymatic activity of
      ribonucleoproteins and possess important advantages relative to PS oligomers in
      both the affinity and the specificity of their recognition. These observations
      should facilitate the development of effective inhibitors of telomerase activity
      and affinity probes of telomerase structure.

PMID- 9630954
TI  - Pathway engineering for the production of aromatic compounds in Escherichia coli.
AB  - Glucose is the preferred substrate for certain fermentation processes. During its
      internalization and concomitant formation of glucose-6-phosphate through the
      glucose phosphotransferase system (PTS), one molecule of phosphoenolpyruvate
      (PEP) is consumed. Together with erythrose 4-phosphate (E4P), PEP is condensed to
      form 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP), the first intermediate
      of the common segment of the aromatic pathway. From this metabolic route, several
      commercially important aromatic compounds can be obtained. We have selected
      Escherichia coli mutants that can transport glucose efficiently by a non-PTS
      uptake system. In theory, this process should increase the availability of PEP
      for other biosynthetic reactions. Using these mutants, in a background where the
      DAHP synthase (the enzyme that catalyzes the condensation of PEP and E4P into
      DAHP) was amplified, we were able to show that at least some of the PEP saved
      during glucose transport, can be redirected into the aromatic pathway. This
      increased carbon commitment to the aromatic pathway was enhanced still further
      upon amplification of the E. coli tktA gene that encodes for a transketolase
      involved in the biosynthesis of E4P.

PMID- 9630955
TI  - Establishment of an Agrobacterium-mediated transformation system for grape (Vitis
      vinifera L.): the role of antioxidants during grape-Agrobacterium interactions.
AB  - Very short exposures of embryogenic calli of Vitis vinifera cv. Superior Seedless
      grape plants to diluted cultures of Agrobacterium resulted in plant tissue
      necrosis and subsequent cell death. Antibiotics used for Agrobacterium
      elimination or as plant selectable markers were not responsible for this necrotic
      response. Rather, cell death seemed to be oxygen-dependent and correlated with
      elevated levels of peroxides. Therefore, we studied the effects on necrosis of
      various combinations of antioxidants during and after grape-Agrobacterium
      cocultivation. The combination of polyvinylpolypyrrolidone and dithiothreitol was
      found to improve plant viability. Tissue necrosis was completely inhibited by
      these antioxidants while Agrobacterium virulence was not effected. These
      treatments enabled the recovery of stable transgenic grape plants resistant to
      hygromycin.

PMID- 9630956
TI  - Translational level is a critical factor for the secretion of heterologous
      proteins in Escherichia coli.
AB  - A method for enhancing the secretion of heterologous proteins in Escherichia coli
      by optimizing, as opposed to simply maximizing, the translational level of a
      given protein is described. Random alteration of the translational initiation
      region (TIR) of the Heat-Stable Enterotoxin II (STII) signal sequence resulted in
      a library of vectors with varied translational strengths. Subsequent screening of
      this library using E. coli alkaline phosphatase as a reporter led to the
      selection of several TIR variants covering a 10-fold range of translational
      strength. These TIR variants, in combination with several previously generated
      variants, are shown to dramatically improve the secretion of a number of
      heterologous proteins. In fact, the heterologous proteins tested required a
      narrow translational range for optimal high-level secretion into the periplasm.
      Interestingly, the secretion of two native E. coli proteins was unaffected by TIR
      strength when tested over an identical range. The dependence of secretion on a
      narrow translational level demonstrates its critical role in the secretion of
      heterologous proteins in E. coli.

PMID- 9630957
TI  - Bioaccumulation of nickel by intercalation into polycrystalline hydrogen uranyl
      phosphate deposited via an enzymatic mechanism.
AB  - A Citrobacter sp. accumulates uranyl ion (UO2(2+)) as crystalline HUO2PO4.4H2O
      (HUP), using enzymatically generated inorganic phosphate. Ni was not removed by
      this mechanism, but cells already loaded with HUP removed Ni2+ by intercalative
      ion-exchange, forming Ni(UO2PO4)2.7H2O, as concluded by x-ray diffraction (XRD)
      and proton induced x-ray emission (PIXE) analyses. The loaded biomass became
      saturated with Ni rapidly, with a molar ratio of Ni:U in the cellbound deposit of
      approx. 1:6; Ni penetration was probably surface-localized. Cochallenge of the
      cells with Ni2+ and UO2(2+), and glycerol 2-phosphate (phosphate donor for
      phosphate release and metal bioprecipitation) gave sustained removal of both
      metals in a flow through bioreactor, with more extensively accumulated Ni. We
      propose 'Microbially Enhanced Chemisorption of Heavy Metals' (MECHM) to describe
      this hybrid mechanism of metal bioaccumulation via intercalation into preformed,
      biogenic crystals, and note also that MECHM can promote the removal of the
      transuranic radionuclide neptunium, which is difficult to achieve by conventional
      methods.

PMID- 9630958
TI  - Expression of a cyanobacterial delta 6-desaturase gene results in gamma-linolenic
      acid production in transgenic plants.
AB  - Gamma-linolenic acid (GLA), a nutritionally important fatty acid in human and
      animal diets, is not produced in oil seed crops. Many oil seed plants, however,
      produce significant quantities of linoleic acid, a fatty acid that could be
      converted to GLA by the enzyme delta 6-desaturase if it were present. As a first
      step to producing GLA in oil seed crops, we have cloned a cyanobacterial delta 6
      desaturase gene. Expression of this gene in transgenic tobacco resulted in GLA
      accumulation. Octadecatetraenoic acid, a highly unsaturated, industrially
      important fatty acid, was also found in transgenic tobacco plants expressing the
      cyanobacterial delta 6-desaturase. This is the first example of engineering the
      production of 'novel' polyunsaturated fatty acids in transgenic plants.

PMID- 9630959
TI  - Field tolerance to fungal pathogens of Brassica napus constitutively expressing a
      chimeric chitinase gene.
AB  - Constitutive overexpression of a protein involved in plant defense mechanisms to
      disease is one of the strategies proposed to increase plant tolerance to fungal
      pathogens. A hybrid endochitinase gene under a constitutive promoter was
      introduced by Agrobacterium-mediated transformation into a winter-type oilseed
      rape (Brassica napus var. oleifera) inbred line. Progeny from transformed plants
      was challenged using three different fungal pathogens (Cylindrosporium
      concentricum, Phoma lingam, Sclerotinia sclerotiorum) in field trials at two
      different geographical locations. These plants exhibited an increased tolerance
      to disease as compared with the nontransgenic parental plants.

PMID- 9630960
TI  - "Complementary" advances in baculovirus recombinant protein expression systems.

PMID- 9630961
TI  - Improved removal of viruslike particles from purified monoclonal antibody IgM
      preparation via virus filtration.

PMID- 9630962
TI  - Cell and tissue culture on the Web.

PMID- 9630963
TI  - Transforming the root of the problem.

PMID- 9630964
TI  - Can ELSI's principles inform consensus?

PMID- 9630965
TI  - Integrating maps requires integrated data.

PMID- 9630966
TI  - Consensus, common entry, and community curation.

PMID- 9630967
TI  - Another salvo in the plant patent wars.

PMID- 9630968
TI  - Monitoring transgenic plants using in vivo markers.

PMID- 9630969
TI  - EC and US agencies fund large-scale Arabidopsis sequencing.

PMID- 9630970
TI  - Milestones in crop biotechnology--transgenic cassava and Agrobacterium-mediated
      transformation of maize.

PMID- 9630972
TI  - Looking for protein family members.

PMID- 9630971
TI  - Special delivery for peptide-stimulated immunity.

PMID- 9630973
TI  - TNF alpha: shock-free cancer remission.

PMID- 9630974
TI  - Peptide mimetic drugs: a comment on progress and prospects.

PMID- 9630975
TI  - Virtually sequenced: the next genomic generation.

PMID- 9630976
TI  - The industrialization of plant transformation.

PMID- 9630977
TI  - The lysis of Trypanosoma brucei brucei by human serum.
AB  - The natural immunity of humans to the cattle pathogen Trypanosoma brucei brucei,
      but not to the morphologically indistinguishable human pathogens T. brucei
      gambiense and T. brucei rhodesiense, is due to the selective killing of the
      parasite by normal human serum. The factor in human serum that mediates lysis of
      T. brucei brucei has long been attributed to a minor subclass of high density
      lipoprotein (HDL). Evidence indicates that the trypanolytic activity of isolated
      human HDL is due to peroxidase activity of an associated haptoglobin-related
      protein-hemoglobin complex. However, recent data suggest that the trypanolytic
      activity of HDL may be completely inhibited in whole human serum, and that
      trypanolytic activity of norman human serum is due to a second, less well-defined
      factor of high molecular weight. Current research aimed at understanding the
      mechanisms of cytotoxicity and the affected metabolic pathways may open new
      approaches for the development of specific drugs and vaccines against
      trypanosomiasis.

PMID- 9630979
TI  - Development of friable embryogenic callus and embryogenic suspension culture
      systems in cassava (Manihot esculenta Crantz)
AB  - Procedures for the production of a new and highly prolific embryogenic culture
      system have been developed in cassava. The importance of the basal salts and type
      of auxin in controlling the development of cassava embryogenic tissues has been
      demonstrated, with culture on Gresshoff and Doy basal medium in the presence of 4
      amino-3,5,6,trichloro-picolinic acid (picloram) inducing the formation of friable
      embryogenic callus from which highly totipotent embryogenic suspension cultures
      could be established. Plants have been regenerated from these cultures. The
      availability of embryogenic suspension cultures is considered to have important
      implications for the application of genetic transformation and other
      biotechnologies in the agronomic improvement of cassava.

PMID- 9630978
TI  - Immunopotency of a viral peptide assembled on the carbohydrate moieties of self
      immunoglobulins.
AB  - The T-cell receptor recognizes peptides bound to the major histocompatibility
      complex antigens. Synthetic peptides corresponding to microbial epitopes can
      efficiently stimulate the in vitro proliferation of T-cell hybridoma or in vivo
      primed T cells. However, the in vivo immune responses elicited by synthetic
      peptides are weak because of their short half-life and poor immunogenicity. We
      previously showed that a genetically engineered immunoglobulin (Ig-HA), in which
      the CDR3 region of VH gene was replaced with a viral peptide recognized by CD4+ T
      cells, was able to deliver this epitope in the correct frame to antigen
      processing cells that efficiently presented the peptide to T cells. Recently, we
      developed an enzymatic method to assemble viral peptides on the sugar moieties of
      immunoglobulins without alteration of the biological functions of either
      molecule. The viral peptide carried by these conjugates was twenty times more
      efficient in activating a T-cell hybridoma than the free peptide as calculated on
      a molar basis. We show that such conjugates are able to prime in vivo the
      precursors of peptide-specific T cells and to induce proliferation of naive
      lymphocytes from transgenic mice expressing a peptide-specific T-cell receptor in
      both CD4 and CD8 T-cell subsets. Our results suggest that peptides enzymatically
      linked to the carbohydrate moieties of immunoglobulins, using galactose residues
      as peptide acceptor, can be used as a safe and efficient delivery system of
      protective epitopes for the prevention of infectious diseases. The enzymatic
      engineering of immunoglobulins may also allow the development of
      immunotherapeutic agents to deliver antagonist peptides to autoreactive T cells
      or to direct immunomodulatory agents such as interleukins or cytolytic drugs to
      tumor cells.

PMID- 9630980
TI  - Regeneration of transgenic cassava plants (Manihot esculenta Crantz) from
      microbombarded embryogenic suspension cultures.
AB  - A protocol was established for the introduction of DNA into embryogenic
      suspension-derived tissues of cassava via microparticle bombardment, for the
      selection of genetically transformed cells, and for the regeneration of fully
      transgenic plants from these cells. The plasmid DNA used for bombardment
      contained a gene encoding neomycin phosphotransferase (nptII) and a gene encoding
      beta-glucuronidase (uidA). Selection of bombarded tissue with paromomycin
      resulted in the establishment of putative transgenic embryogenic calli. In most
      of these calli, beta-glucuronidase was detected histochemically. Molecular
      analysis of paromomycin-resistant embryogenic calli and of plants regenerated
      from these calli, confirmed the stable integration of bombarded DNA into the
      cassava genome.

PMID- 9630981
TI  - Genetic transformation of cassava (Manihot esculenta Crantz).
AB  - Genetic engineering can be used to complement traditional breeding methods in
      crop plant improvement. Transfer of genes from heterologous species provides the
      means of selectively introducing new traits into crop plants and expanding the
      gene pool beyond what has been available to traditional breeding systems. The
      prerequisites for genetic engineering are efficient transformation and tissue
      culture systems that allow selection and regeneration of transgenic plants.
      Cassava, an integral plant for food security in developing countries, has until
      now been recalcitrant to transformation approaches. We report here a method for
      regenerating stably transformed cassava plants after cocultivation with
      Agrobacterium tumefaciens, which opens cassava for future improvement via
      biotechnology.

PMID- 9630982
TI  - Cloning of ligand targets: systematic isolation of SH3 domain-containing
      proteins.
AB  - Based on the prevalence of modular protein domains, such as Src homology domain 3
      and 2 (SH3 and SH2), among important signaling molecules, we have sought to
      identify new SH3 domain-containing proteins. However, modest sequence similarity
      among these domains restricts the use of DNA-based methods for this purpose. To
      circumvent this limitation, we have developed a functional screen that permits
      the rapid cloning of modular domains based on their ligand-binding activity.
      Using operationally defined SH3 ligands from combinatorial peptide libraries, we
      screened a series of mouse and human cDNA expression libraries. We found that 69
      of the 74 clones isolated encode at least one SH3 domain. These clones encode 18
      different SH3-containing proteins, 10 of which have not been described
      previously. The isolation of entire repertoires of modular domain-containing
      proteins will prove invaluable in genome analysis and in bringing new targets
      into drug discovery programs.

PMID- 9630983
TI  - High efficiency transformation of maize (Zea mays L.) mediated by Agrobacterium
      tumefaciens.
AB  - Transformants of maize inbred A188 were efficiently produced from immature
      embryos cocultivated with Agrobacterium tumefaciens that carried "super-binary"
      vectors. Frequencies of transformation (independent transgenic plants/embryos)
      were between 5% and 30%. Almost all transformants were normal in morphology, and
      more than 70% were fertile. Stable integration, expression, and inheritance of
      the transgenes were confirmed by molecular and genetic analysis. Between one and
      three copies of the transgenes were integrated with little rearrangement, and the
      boundaries of T-DNA were similar to those in transgenic dicotyledons and rice. F1
      hybrids between A188 and five other inbreds were transformed at low frequencies.

PMID- 9630984
TI  - Affinity-assisted in vivo folding of a secreted human peptide hormone in
      Escherichia coli.
AB  - We show that coexpression of a specific binding protein in Escherichia coli can
      significantly improve the relative yields of correctly folded human insulin-like
      growth factor I (IGF-I). A glutathione redox buffer was used during growth to
      allow formation and breakage of disulfide bonds in the periplasm of the bacterial
      host. Both the binding protein and the peptide hormone were produced as affinity
      fusions, which allowed purification of the in vivo formed heterodimer by
      alternative affinity purification methods. The use of affinity-assisted in vivo
      folding has general implications for expression, folding, and purification of
      recombinant proteins.

PMID- 9630985
TI  - Increased xylanase yield in Streptomyces lividans: dependence on number of
      ribosome-binding sites.
AB  - The Streptomyces lividans xylanase A (XlnA) signal peptide (sp) was replaced with
      the signal peptides of either mannanase A (ManA) or cellulase A (CelA), two
      enzymes secreted by S. lividans. Depending on the location of the ribosome
      binding sites (RBS) with respect to a potential initiation codon, the length of
      the putative sps of ManA and CelA is either 34 or 43 amino acids and 27 or 46
      amino acids, respectively. The sequence encoding these sps were fused to the
      xylanase A gene (xlnA). Clones harboring the short sps of ManA and CelA produced
      as much xylanase as the clone with the control wild-type sp sequence of XlnA. In
      clones containing the long sps of ManA and CelA, the XlnA production was enhanced
      1.5- and 2.5-fold, respectively. These XlnA yields are reduced by half and one
      third respectively when the internal initiation codons of the long sp sequences
      of ManA and CelA are mutated. Since these clones exhibited the same transcription
      levels, the results indicate that both RBSs are used concomitantly in S. lividans
      to increase the enzyme production at the translational level. However, when the
      short and long sps of ManA were fused to the long CelA sp sequence, giving
      constructs containing respectively 3 and 4 RBSs, a decrease in xylanase
      production was observed.

PMID- 9630986
TI  - pH-sensitive, cationic liposomes: a new synthetic virus-like vector.
AB  - We describe the use of cationic, pH-sensitive liposomes to mediate the efficient
      transfer of DNA into a variety of cells in culture. Cationic lipids, containing
      an amine with a pK within the physiologic range of 4.5 to 8, were synthesized and
      incorporated with dioleoylphosphatidylethanolamine into liposomes. Acid
      conditions promoted DNA-binding, DNA-incorporation, and DNA-induced fusion by
      these cationic, pH-sensitive liposomes. Transfection efficiency in cultured cells
      was dependent on endosomal acidification in a manner akin to acidic-induced
      endosomal release of viruses. These liposomes constitute a promising new class of
      reagents for gene therapy.

PMID- 9630987
TI  - An Escherichia coli hemolysin transport system-based vector for the export of
      polypeptides: export of Shiga-like toxin IIeB subunit by Salmonella typhimurium
      aroA.
AB  - The export of Escherichia coli hemolysin across the cytoplasmic and the outer
      membranes requires the COOH-terminal signal sequence of HlyA, the two specific
      translocator proteins HlyB and HlyD, and the outer membrane protein TolC. We have
      developed an export cloning system that is composed of two vectors: one in which
      the fusion of the desired gene with the 3'-end of hlyA is generated, and a second
      in which the sequences containing the fusion are combined with the accessory
      genes hlyB and hlyD, thereby reconstructing the natural organization of the hly
      locus. In the second vector the fusion and the accessory genes are flanked by
      Notl sites, allowing subcloning of the whole cluster into a variety of
      minitransposons to achieve the stable integration of the constructs into the
      chromosome of Gram-negative bacteria. Since some applications may require the
      production of transcriptional fusions, an alternative version of the system
      provides the efficient translation initiation region of T7 phage gene 10 upstream
      of the fusion protein coding sequence. The usefulness of the system was assessed
      by constructing a fusion between the gene encoding the B subunit of Shiga-like
      toxin lle and the 3'-end of hlyA. An attenuated Salmonella typhimurium vaccine
      strain harboring the resulting construct, either in multicopy or monocopy,
      efficiently expressed and exported the chimeric protein. We anticipate that this
      system will lead to a higher stability of the engineered function and permit a
      faithful monitoring of the export of the recombinant peptide under physiologic
      single-copy conditions.

PMID- 9630988
TI  - Building your company around your clinical trials team.

PMID- 9630989
TI  - The new section 103(b) of the patent law: an obvious solution?

PMID- 9630990
TI  - Biohydrogen production deserves serious funding.

PMID- 9630991
TI  - Ripen-on-command: in a society with ample food, why bother?

PMID- 9630992
TI  - Produce-on-demand: what's good for US markets is good for world markets too.

PMID- 9630993
TI  - Biosafety protocol draft spooks US biotechnology officials.

PMID- 9630994
TI  - Host-defense peptides.

PMID- 9630995
TI  - Software on the Internet.

PMID- 9630996
TI  - Arabidopsis sequencing.

PMID- 9630997
TI  - Berlex continues legal challenge to FDA over MS drug.

PMID- 9630998
TI  - Is British Biotech's Marimastat a major cancer drug?

PMID- 9630999
TI  - It's not the size, it's the potency.

PMID- 9631000
TI  - Generating high-avidity human Mabs in mice.

PMID- 9631001
TI  - Suicidal tumor proteases.

PMID- 9631002
TI  - Databases for gene expression.

PMID- 9631003
TI  - Silent genes and everlasting fruits and vegetables?

PMID- 9631004
TI  - Immune system under assault in Massachusetts.

PMID- 9631005
TI  - Biotechnology and the UN: new challenges, new failures.

PMID- 9631006
TI  - Refining the telomere-telomerase hypothesis of aging and cancer.
AB  - While there has been substantial experimental evidence in support of the telomere
      telomerase hypothesis of aging and cancer, it has been suggested that the theory
      has been oversimplified to the exclusion of alternative mechanisms in the
      progression of cancer. This review strives to present an overview of some of the
      areas that have not been well explained and to indicate where multiple
      interpretations of the data are possible.

PMID- 9631007
TI  - Potent and selective inhibition of gene expression by an antisense
      heptanucleotide.
AB  - Factors that govern the specificity of an antisense oligonucleotide (ON) for its
      target RNA include accessibility of the targeted RNA to ON binding, stability of
      ON/RNA complexes in cells, and susceptibility of the ON/RNA complex to RNase H
      cleavage. ON specificity is generally proposed to be dependent on its length. To
      date, virtually all previous antisense experiments have used 12-25 nt-long ONs.
      We explored the antisense activity and specificity of short (7 and 8 nt) ONs
      modified with C-5 propyne pyrimidines and phosphorothioate internucleotide
      linkages. Gene-selective, mismatch sensitive, and RNase H-dependent inhibition
      was observed for a heptanucleotide ON. We demonstrated that the flanking
      sequences of the target RNA are a major determinant of specificity. The use of
      shorter ONs as antisense agents has the distinct advantage of simplified
      synthesis. These results may lead to a general, cost-effective solution to the
      development of antisense ONs as therapeutic agents.

PMID- 9631008
TI  - High-avidity human IgG kappa monoclonal antibodies from a novel strain of
      minilocus transgenic mice.
AB  - Human immunoglobulin transgenic mice provide a method of obtaining human
      monoclonal antibodies (Mabs) using conventional hybridoma technology. We describe
      a novel strain of human immunoglobulin transgenic mice and the use of this strain
      to generate multiple high-avidity human sequence IgG kappa Mabs directed against
      a human antigen. The light chain transgene is derived in part from a yeast
      artificial chromosome clone that includes nearly half of the germline human V
      kappa region. In addition, the heavy-chain transgene encodes both human mu and
      human gamma 1 constant regions, the latter of which is expressed via
      intratransgene class switching. We have used these animals to isolate human IgG
      kappa Mabs that are specific for the human T-cell marker CD4, have high binding
      avidities, and are immunosuppressive in vitro. The human Mab-secreting hybridomas
      display properties similar to those of wild-type mice including stability,
      growth, and secretion levels. Mabs with four distinct specificities were derived
      from a single transgenic mouse, consistent with an extensive diversity in the
      primary repertoire encoded by the transgenes.

PMID- 9631009
TI  - Tumor protease-activated, pore-forming toxins from a combinatorial library.
AB  - We describe a library of two-chain molecular complementation mutants of
      staphylococcal alpha-hemolysin that features a combinatorial cassette encoding
      thousands of protease recognition sites in the central pore-forming domain. The
      cassette is flanked by a peptide extension that inactivates the protein. We
      screened the library to identify alpha-hemolysins that are highly susceptible to
      activation by cathepsin B, a protease that is secreted by certain metastatic
      tumor cells. Toxins obtained by this procedure should be useful for the
      permeabilization of malignant cells thereby leading directly to cell death or
      permitting destruction of the cells with drugs that are normally membrane
      impermeant.

PMID- 9631010
TI  - Selective amplification of protein-coding regions of large sets of genes using
      statistically designed primer sets.
AB  - We describe a novel approach to design a set of primers selective for large
      groups of genes. This method is based on the distribution frequency of all
      nucleotide combinations (octa- to decanucleotides), and the combined ability of
      primer pairs, based on these oligonucleotides, to detect genes. By analyzing 1000
      human mRNAs, we found that a surprisingly small subset of octanucleotides is
      shared by a high proportion of human protein-coding region sense strands. By
      computer simulation of polymerase chain reactions, a set based on only 30 primers
      was able to detect approximately 75% of known (and presumably unknown) human
      protein-coding regions. To validate the method and provide experimental support
      for the feasibility of the more ambitious goal of targeting human protein-coding
      regions, we sought to apply the technique to a large protein family: G-protein
      coupled receptors (GPCRs). Our results indicate that there is sufficient low
      level homology among human coding regions to allow design of a limited set of
      primer pairs that can selectively target coding regions in general, as well as
      genomic subsets (e.g., GPCRs). The approach should be generally applicable to
      human coding regions, and thus provide an efficient method for analyzing much of
      the transcriptionally active human genome.

PMID- 9631011
TI  - Expression of ACC oxidase antisense gene inhibits ripening of cantaloupe melon
      fruits.
AB  - The plant hormone ethylene plays a major role in the ripening of climacteric
      fruit. We have generated transgenic cantaloupe Charentais melons expressing an
      antisense ACC oxidase gene; ACC oxidase catalyzes the last step of ethylene
      biosynthesis. Ethylene production of transgenic fruit was < 1% of control
      untransformed fruit, and the ripening process was blocked both on and off the
      vine. The antisense phenotype could be reversed by exogenous ethylene treatment.
      Analysis of antisense ACC oxidase melons indicated that the ripening process
      includes ethylene-dependent and ethylene-independent pathways. Because the
      transgenic line we generated displays extended storage life and improved quality,
      it has a promising potential for commercial development.

PMID- 9631012
TI  - High-level expression of recombinant human fibrinogen in the milk of transgenic
      mice.
AB  - Fibrinogen is a complex plasma protein composed of two each of three different
      polypeptide chains. We have targeted expression of r-human fibrinogen to the
      mammary gland of transgenic mice. Three expression cassettes, each containing the
      genomic sequence for one of the three human fibrinogen chains controlled by sheep
      whey protein beta-lactoglobulin promoter sequences, were coinjected into fertile
      mouse eggs. Southern blot analysis demonstrated that more than 80% of the
      transgenic founders contained all three fibrinogen genes. Reducing sodium dodecyl
      sulfate polyacrylamide gel electrophoresis of milk from the highest producing
      founder animal demonstrated the presence of human fibrinogen subunits at
      concentrations of 2000 micrograms/ml. In several animals with a balanced ratio of
      the individual fibrinogen subunits, up to 100% of the protein was incorporated
      into fully assembled fibrinogen hexamers. Incubation of the transgenic milk with
      thrombin and factor XIII resulted in a cross-linked fibrin clot, indicating that
      a major portion of the secreted fibrinogen was functional. These studies
      represent the first report of high-level biosynthesis and secretion of a
      functional, complex, hexameric protein in the milk of a transgenic animal.

PMID- 9631013
TI  - In vitro hydrogen production by glucose dehydrogenase and hydrogenase.
AB  - A new in vitro enzymatic pathway for the generation of molecular hydrogen from
      glucose has been demonstrated. The reaction is based on the oxidation of glucose
      by Thermoplasma acidophilum glucose dehydrogenase with the concomitant oxidation
      of NADPH by Pyrococcus furiosus hydrogenase. Stoichiometric yields of hydrogen
      were produced from glucose with the continuous recycling of cofactor. This simple
      system may provide a method for the biological production of hydrogen from
      renewable sources. In addition, the other product of this reaction, gluconic
      acid, is a high-value chemical commodity.

PMID- 9631014
TI  - Expression of a novel high-molecular-weight glutenin subunit gene in transgenic
      wheat.
AB  - High-molecular-weight glutenin subunits (HMW-GS), one class of seed storage
      proteins, are important determinants of the bread-making quality of wheat flour.
      To change the amount and composition of these proteins via genetic engineering, a
      gene encoding a novel hybrid subunit under the control of native HMW-GS
      regulatory sequences was inserted into wheat. Of 26 independent transgenic lines
      identified by bialaphos selection, 18 expressed the cotransformed hybrid HMW-GS
      gene in their seed. The hybrid subunit accumulated to levels comparable to those
      of the native HMW-GS. These results show that a native HMW-GS gene promoter can
      be used to obtain high levels of expression of seed storage and, potentially,
      other proteins in transgenic wheat endosperm. Transgene expression was stable for
      at least three seed generations in the majority of lines. These experiments
      demonstrate the feasibility of constructing wheat plants with novel seed protein
      compositions.

PMID- 9631015
TI  - Use of microphysiometry for analysis of heterologous ion channels expressed in
      yeast.
AB  - Measurement of extracellular acidification rates by microphysiometry provides a
      means to analyze the function of ion channels expressed in yeast cells. These
      measurements depend on the proton pumping action of the H(+)-ATPase, a central
      component of the yeast plasma membrane. We used microphysiometry to analyze the
      activity of two ion channels expressed in yeast. In one example, an inwardly
      rectifying K+ channel, gpIRK1, provides a potassium uptake function when
      expressed in a potassium transporter-defective yeast strain. Rates of
      acidification in gpIRK1-expressing cells directly reflect channel function.
      Addition of cesium, an inhibitor of gpIRK1 activity, results in an immediate
      reduction in acidification rates. In a second example, expression of a
      nonselective cation channel, the influenza virus M2 protein, is believed to
      interfere with the maintenance of the electrochemical proton gradient by the H(+)
      ATPase. In cells expressing the M2 channel, addition of inhibitors increases the
      rate of proton extrusion. Moreover, functional differences between two M2
      inhibitors, amantadine and BL-1743, are distinguished by the microphysiometer.
      This application demonstrates the utility of the microphysiometer for functional
      studies of ion channels; it is adaptable to a screening process for compounds
      that modulate ion channel activity.

PMID- 9631017
TI  - What Markman should mean to you.

PMID- 9631016
TI  - FACS-based isolation of slowly growing cells: double encapsulation of yeast in
      gel microdrops.
AB  - Isolating hyperproducing cells is important in biotechnology, but these cells
      usually grow slowly and can be overgrown by poorly producing cells. We describe a
      new method of isolating slowly growing cells from among rapidly growing cells,
      which has the potential for automation and high throughput (e.g., 100,000
      cells/h). A model system is presented consisting of a mixed population of slowly
      growing mutant and rapidly growing wild-type yeast, which were encapsulated in
      double agarose gel microdrops (dGMDs); with most dGMDs initially containing
      single cells. Double encapsulation locates parent cells near dGMD centers, making
      microcolony measurement more accurate. After a 15-h incubation, fluorescent
      activated cell sorting was used to analyze and sort dGMDs with small
      microcolonies (slow growers) from dGMDs with large microcolonies (rapid growers).
      Successful isolation of slow growers from a mixed population of predominantly
      rapidly growing Saccharomyces cerevisiae cells was achieved.

PMID- 9631018
TI  - Doppelganger proteins as drug leads.

PMID- 9631019
TI  - Zurich hazard analysis in biotechnology.

PMID- 9631020
TI  - Setting standards for information exchange in drug development.

PMID- 9631021
TI  - Biodiamonds and paying back debts.

PMID- 9631022
TI  - Did George do the right thing?

PMID- 9631023
TI  - US national bioethics commission: politics as usual?

PMID- 9631024
TI  - UK government blows a hollow trumpet.

PMID- 9631025
TI  - Reconstructing the biochemical edifice.

PMID- 9631026
TI  - Cassava R&D: a public investment.

PMID- 9631027
TI  - The adenovirus and the egg: a new approach to transgenesis.

PMID- 9631028
TI  - From curse to cure: HIV for gene therapy?

PMID- 9631029
TI  - NO NMDA receptor activity.

PMID- 9631030
TI  - A new vision for plant productivity.

PMID- 9631031
TI  - Designer oils for better nutrition.

PMID- 9631032
TI  - Metal in restrained means.

PMID- 9631033
TI  - Taking DNA probes into a protein world.

PMID- 9631034
TI  - Getting the glycosylation right: implications for the biotechnology industry.
AB  - Glycosylation is the most extensive of all the posttranslational modifications,
      and has important functions in the secretion, antigenicity and clearance of
      glycoproteins. In recent years major advances have been made in the cloning of
      glycosyltransferase enzymes, in understanding the varied biological functions of
      carbohydrates, and in the accurate analysis of glycoprotein heterogeneity. In
      this review we discuss the impact of these advances on the choice of a
      recombinant host cell line, in optimizing cell culture processes, and in choosing
      the appropriate level of glycosylation analysis for each stage of product
      development.

PMID- 9631035
TI  - Transgenesis by adenovirus-mediated gene transfer into mouse zona-free eggs.
AB  - Zona-free mouse eggs at the pronucleus stage were infected with a replication
      defective adenovirus vector containing a nuclear-targeted lacZ gene. Exogenous
      beta-galactosidase activity was detected in almost all eggs at the two-cell
      stage. Of 27 mice that developed from infected eggs, three carried the integrated
      exogenous gene mediated by the adenovirus. Two of the three expressed the lacZ
      gene, and all three mice transmitted the adenovirus-mediated transgene to F1
      progeny Southern blot analysis was consistent with single copy integration. This
      finding should accelerate the development of new strategies for transgenesis and
      assist studies on the function of cloned genes in vivo.

PMID- 9631036
TI  - In vitro selection of peptides acting at a new site of NMDA glutamate receptors.
AB  - Oligomeric N-methyl D-aspartate receptor (NMDAR) in brain is a ligand-gated ion
      channel that becomes selectively permeable to ions upon binding to ligands. For
      NMDAR channel, the binding of glutamate and glycine results in opening of the
      calcium permeable channel. Because the calcium influx mediated by NMDAR is
      important for synaptic plasticity and excitotoxicity, the function of NMDA
      receptors has been implicated in both health and disease. Native NMDA receptors
      are thought to be heteromeric pentamers with a central ion conduction pathway.
      There are five genes (NR1, 2A, 2B, 2C, and 2D) encoding various subunits that
      have been cloned, and NR1 is thought to be the essential subunit since it forms a
      functional channel by itself. To study NMDAR structure and function, we have
      searched for peptide modulators of NR1 using random peptide bacteriophage
      libraries. The peptides were identified based on their specific association with
      a purified receptor fusion protein that contains the putative ligand binding
      domain. We report the identification of one group of cyclic peptides (Mag-1) with
      a consensus sequence of CDGLRHMWFC. Using biochemical binding analysis and patch
      clamp electrophysiological recording, we show that the synthetic Mag-1 peptides
      cause noncompetitive inhibition of the receptor channel activity.

PMID- 9631038
TI  - Genetic engineering of harvest index in tobacco through overexpression of a
      phytochrome gene.
AB  - The phytochrome photoreceptor family regulates plant architecture in response to
      environmental light signals. Phytochromes mediate the shade avoidance syndrome,
      in which plants react to far-red radiation reflected from neighbors by elongation
      growth, occurring at the expense of leaf and storage organ production. We show
      that transgenic overproduction of phytochrome A in tobacco suppresses shade
      avoidance, causing proximity-conditional dwarfing. At high densities in the
      field, assimilates show an enhanced allocation to leaves, with a concomitant
      increase in harvest index. Transfer of this approach to other crop plants could
      provide significant improvements in productivity.

PMID- 9631037
TI  - In vivo EPR detection and imaging of endogenous nitric oxide in
      lipopolysaccharide-treated mice.
AB  - Nitric oxide (NO), a simple diatomic free radical, is known to play a critical
      physiological role in diverse organisms. An iron complex, with N
      (dithiocarboxy)sarcosine (Fe-DTCS), has a high affinity for endogenous NO and can
      trap, stabilize, and accumulate it. The stable NO adduct thus formed is
      detectable at room temperature with electron paramagnetic resonance (EPR)
      spectrometry. We report in vivo EPR imaging of endogenous NO, trapped by an Fe
      DTCS complex, in the abdomen of a live mouse. To our knowledge, this is the first
      report on EPR imaging of endogenous free radicals produced in vivo. This EPR
      imaging method will be useful for the noninvasive investigation of the spatial
      distribution of NO in pathologic organs or tissues.

PMID- 9631039
TI  - The thermodynamic control of protein binding to lipid bilayers for protein
      chromatography.
AB  - A new concept of charge-selective bioseparation with certain advantages over the
      established ion-exchange technique is reported. The procedure is based on the
      temperature-controlled creation and dispersion of domain structures in single
      phospholipid bilayers by means of the phase transition between the gel phase and
      the fluid phase of the bilayer. The bilayers are presented on a solid support of
      silica gel. Rather than altering the ionic strength of the buffer, protein
      elution is accomplished by a change of the chromatography column temperature. The
      application of temperature gradients improves the protein selectivity of phase
      transition chromatography.

PMID- 9631040
TI  - Low-temperature resistance of higher plants is significantly enhanced by a
      nonspecific cyanobacterial desaturase.
AB  - A broad-specificity delta 9 desaturase gene was cloned from the cyanobacterium
      Anacystis nidulans. The enzyme introduces a cis-double bond at the delta 9
      position of both 16 and 18 carbon saturated fatty acids linked to many kinds of
      membrane lipids. The gene was stably introduced into tobacco plants under
      transcriptional control of the cauliflower mosaic virus 35S promoter, and the
      enzyme was targeted into plastids by the transit peptide of the pea RuBisCO small
      subunit. The transgenic plants had a highly reduced level of saturated fatty acid
      content in most membrane lipids and exhibited a significant increase in chilling
      resistance.

PMID- 9631041
TI  - Streptavidins with intersubunit crosslinks have enhanced stability.
AB  - Natural tetrameric streptavidin has two subunit interfaces; one is a strong
      interface between subunits in a tightly associated dimer, and the other is a weak
      interface between a pair of such dimers (dimer-dimer interface). To test whether
      strengthening the weak dimer-dimer interface could provide streptavidin with
      additional structural stability, covalent crosslinks were introduced between
      adjacent subunits through the dimer-dimer interface. Specific crosslinking sites
      were designed by site-directed mutations of His-127 residues that are in close
      proximity in natural streptavidin. The first and second streptavidin constructs
      have a disulfide bond and an irreversible covalent bond, respectively, between
      two Cys-127 residues across the dimer-dimer interface. The third variant is a
      hybrid tetramer consisting of two different streptavidin species, one having
      lysine and the other aspartic acid at position 127, which are covalently
      crosslinked. All streptavidin constructs with intersubunit crosslinks showed
      higher biotin-binding ability than natural core streptavidin after heat
      treatment. All of these crosslinked streptavidins retained bound biotin more
      stably than natural core streptavidin in guanidine hydrochloride at very acidic
      pH. These results suggest that the introduction of covalent bonds across the
      dimer-dimer interface enhances the overall stability of streptavidin.

PMID- 9631042
TI  - A method to codetect introduced genes and their products in gene therapy
      protocols.
AB  - To monitor the presence of introduced genes and the distribution of the encoded
      proteins in host tissues after gene transfer, we combined fluorescence in situ
      hybridization (FISH) and immunohistochemistry in two separate gene therapy
      paradigms. In brain tissue sections from animals injected with pHSVlac vector, we
      localized nuclei containing vector DNA both in cells expressing and not
      expressing beta-galactosidase (beta-gal). This suggests that the efficiency of
      gene transfer is affected not only by gene delivery, but also by cellular
      controls on gene expression. In a second paradigm, following myoblast
      transplantation, we detected donor nuclei in the muscle of a patient with
      Duchenne's muscular dystrophy. The donor nuclei were either surrounded by host
      nuclei or apparently fused in the patient's muscle fiber producing dystrophin.
      The combined FISH and immunohistochemistry assay offers greater sensitivity and
      more information than currently used polymerase chain reaction and protein
      detection methods.

PMID- 9631044
TI  - An enzyme-linked oligonucleotide assay.
AB  - The recent development of in vitro methods to select high-affinity ligands by
      combinatorial chemistry methodologies promises unique and theoretically unlimited
      supplies of novel therapeutic and diagnostic reagents. One such combinatorial
      chemistry process, systematic evolution of ligands by exponential enrichment
      (SELEX), allows rapid identification, from large random sequence pools, of the
      few oligonucleotide sequences that bind to a desired target molecule with high
      affinity and specificity. We describe an enzyme-linked sandwich assay that uses a
      SELEX-derived oligonucleotide. This assay demonstrates that these
      oligonucleotides can be effective and useful analytical reagents.

PMID- 9631043
TI  - Enhanced metalloadsorption of bacterial cells displaying poly-His peptides.
AB  - The properties of Escherichia coli cells, acquired by cell surface presentation
      of one or two hexahistidine (His) clusters carried by the outer membrane LamB
      protein, have been examined. Strains producing LamB hybrids with the His chains
      accumulated greater than 11-fold more Cd2+ than E. coli cells expressing the
      protein without the His insert. Furthermore, the hexa-His chains on the cell
      surface caused cells to adhere reversibly to a Ni(2+)-containing solid matrix in
      a metal-dependent fashion. Thus, expression of poly-His peptides enables bacteria
      to act as a metalloaffinity adsorbent. These results open up the possibility for
      biosorption of heavy ions using engineered microorganisms.

PMID- 9631045
TI  - Patent pitfalls among the unpredictable arts.

PMID- 9631046
TI  - Solving the "taxol dilemma".

PMID- 9631047
TI  - Nomenclature on the fly.

PMID- 9631048
TI  - Delaney clause knocked out by surprise compromise act.

PMID- 9631049
TI  - Classifying transgenics.

PMID- 9631051
TI  - Sequana worms ahead of the pack.

PMID- 9631052
TI  - Reflections on mirrors.

PMID- 9631053
TI  - Taxol production in plant cell culture comes of age.

PMID- 9631054
TI  - Sequence from spectrometry: a realistic prospect?

PMID- 9631055
TI  - Sweeter times ahead for sugarbeet growers.

PMID- 9631056
TI  - Minimized hormones grow in stature.

PMID- 9631057
TI  - Painless PCR.

PMID- 9631058
TI  - Combating consumption.

PMID- 9631059
TI  - Hydrogen biotechnology: progress and prospects.

PMID- 9631060
TI  - Encapsulated cell technology.
AB  - The potential therapeutic applications of encapsulated cells are enormous. In the
      US alone, it has been estimated that nearly half-a-trillion dollars are spent
      each year to care for patients who suffer tissue loss or dysfunction. Over 6
      million patients suffer from neurodegenerative disorders such as Alzheimer's
      disease and Parkinson's disease, over 14 million patients suffer from diabetes,
      and millions more from liver failure, hemophilia, and other diseases caused by
      the loss of specific vital cellular functions. It appears likely that by the end
      of the decade clinical trials of encapsulated cells to treat many of these
      diseases will become a reality. The Food and Drug Administration has already
      authorized studies to evaluate the safety and biological activity of several
      types of systems. A number of issues will have to be addressed, including the
      sourcing of raw materials, the design and building of manufacturing facilities,
      the scale-up and optimization process, storage and distribution of the product,
      and quality control.

PMID- 9631061
TI  - Mirror-image RNA that binds D-adenosine.
AB  - A 58-mer L-RNA ligand that binds to naturally occurring D-adenosine with a
      dissociation constant of 1.7 microM in solution was identified from a
      combinatorial library employing mirror-design. The corresponding D-RNA ligand
      shows identical binding affinity to L-adenosine. Reciprocal chiral specificity
      was also evident from ligand discrimination; the binding affinity of the L-RNA
      ligand for D-adenosine was 9000-fold greater than its affinity for L-adenosine
      and vice versa. While the D-RNA ligand was rapidly degraded in human serum, the L
      RNA ligand displayed an extraordinary stability. This indicates the potential
      application of specifically designed L-RNA ligands as stable monoclonal antibody
      analogues and the development of highly stable L-ribozymes.

PMID- 9631062
TI  - Mirror-design of L-oligonucleotide ligands binding to L-arginine.
AB  - The high affinity and selectivity of nucleic acid ligands have clearly
      demonstrated that RNA can be targeted to a variety of molecules. In practice,
      however, the use of unmodified aptamers is impeded by the low stability of RNA in
      biological fluids. Here we describe the mirror-design of a stable 38-mer L
      oligoribonucleotide ligand that binds to L-arginine. This L-RNA ligand was also
      able to bind to a short peptide containing the basic region of the human
      immunodeficiency virus type-1 Tat-protein. The L-RNA ligand displayed the
      expected stability in human serum. These findings may contribute to the
      identification of novel diagnostics and pharmaceuticals.

PMID- 9631063
TI  - Small molecule nerve growth factor analogs image receptors in vivo.
AB  - The in vivo targeting efficacy of small molecule analogs of nerve growth factor
      (NGF) that bind the NGF receptor p140 TrkA was evaluated and compared with that
      of a high-affinity anti-TrkA monoclonal antibody (Mab 5C3). Nuclear imaging
      studies were done after the injection of 99mTc-labeled compounds in nude mice
      bearing tumors. Kinetics of tumor targetting, blood clearance, and
      bioavailability of NGF mimics were equivalent or better than Mab 5C3. Tumors that
      do not express TrkA were not targeted, demonstrating the specificity of NGF
      mimics in vivo. This comparative biodistribution study demonstrates that receptor
      specific small molecule analogs designed from large polypeptides may be more
      useful than antibodies and may be effective agents for the detection, diagnosis,
      and possible treatment of neoplasias involving overexpressed oncogenic receptors
      such as TrkA.

PMID- 9631064
TI  - A strategy for rapid and efficient DNA sequencing by mass spectrometry.
AB  - Two methods of solid-phase Sanger DNA sequencing followed by detection with
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry are
      demonstrated. In one method, sequencing ladders generated on an immobilized
      synthetic template were resolved up to the 63-mer including the primer. Detection
      sensitivity and resolution were sufficient for sequence analysis in the given
      range. This approach is particularly suitable for comparative (diagnostic) DNA
      sequencing. A second method that has the potential for high throughput de novo
      DNA sequencing is also presented; it uses immobilized duplex probes with five
      base single-stranded overhangs to capture an unknown DNA template serving as
      primers for Sanger DNA sequencing. The power of mass spectrometry is demonstrated
      not only by its very high speed, but also by its ability to identify sequences
      that are not readable using gel electrophoresis.

PMID- 9631065
TI  - Methyl jasmonate-induced overproduction of paclitaxel and baccatin III in Taxus
      cell suspension cultures.
AB  - Taxus cell culture may be an alternative source of paclitaxel and related taxane
      production. Significantly increased amounts of paclitaxel and baccatin III were
      observed in cultured cells of Taxus species after exposure to methyl jasmonate.
      Among the three species of Taxus tested, Taxus media showed the highest
      paclitaxel content while Taxus baccata showed the highest baccatin III content
      when 100 microM of methyl jasmonate was added to the culture media. Furthermore,
      the activities of methyl jasmonate and related substances for inducing paclitaxel
      production were compared in cell suspension cultures of T. media. Methyl
      jasmonate and its free acid showed the strongest promoting activity. Reduction of
      the keto group at the C-3 position greatly reduced this activity. cis-Jasmone,
      which does not have a carboxyl group at the C-1 position, had almost no activity.
      These results suggest that these two regions of methyl jasmonate are important
      for promoting the production of paclitaxel and related taxanes in Taxus cell
      cultures.

PMID- 9631066
TI  - A high efficiency technique for the generation of transgenic sugar beets from
      stomatal guard cells.
AB  - An optimized protocol has been developed for the efficient and rapid genetic
      modification of sugar beet (Beta vulgaris L.). A polyethylene glycol-mediated DNA
      transformation technique could be applied to protoplast populations enriched
      specifically for a single totipotent cell type derived from stomatal guard cells,
      to achieve high transformation frequencies. Bialaphos resistance, conferred by
      the pat gene, produced a highly efficient selection system. The majority of
      plants were obtained within 8 to 9 weeks and were appropriate for plant breeding
      purposes. All were resistant to glufosinate-ammonium-based herbicides. Detailed
      genomic characterization has verified transgene integration, and progeny analysis
      showed Mendelian inheritance.

PMID- 9631068
TI  - Identification of transgenic mice by PCR analysis of saliva.
AB  - As an alternative to surgically obtaining samples (e.g., tail or tissue biopsy,
      toe dock, or blood sampling) from weanling mice to screen for transgene
      integration or other genetic monitoring procedures, we offer a simpler,
      nonsurgical method. A small amount of saliva, obtained from weanling mice by oral
      wash using a plastic pipet tip, contains enough oral epithelial cells and
      lymphocytes to yield sufficient DNA for nested primer polymerase chain reaction
      (PCR) analysis. The procedure can be repeated many times with minimal stress to
      the animal, in contrast to tissue biopsy procedures such as tail cutting. Sample
      analysis is rapid and straightforward; saliva is applied to sample collection
      paper and then purified using a solid phase DNA purification system. The paper,
      containing purified DNA, is added directly to PCR cocktail for the first round of
      amplification. For weanling mice, in the second round of amplification, a small
      amount of product from the first round is removed and added to PCR cocktail
      containing the second set of primers. With adult mice, an adequate volume of
      saliva may be obtained (dependent upon the sensitivity of the particular
      reaction) to eliminate the need for second-round amplification with nested
      primers. This technique is reliable, does not require organic solvents, and is
      more humane than protocols currently in use. Furthermore, this technique could
      replace hundreds of thousands of surgical biopsies on rodents annually, which are
      performed for both transgene determination and genetic monitoring procedures.

PMID- 9631067
TI  - Elucidation of gene function using C-5 propyne antisense oligonucleotides.
AB  - Identification of human disease-causing genes continues to be an intense area of
      research. While cloning of genes may lead to diagnostic tests, development of a
      cure requires an understanding of the gene's function in both normal and diseased
      cells. Thus, there exists a need for a reproducible and simple method to
      elucidate gene function. We evaluate C-5 propyne pyrimidine modified
      phosphorothioate antisense oligonucleotides (ONs) targeted against two human cell
      cycle proteins that are aberrantly expressed in breast cancer: p34cdc2 kinase and
      cyclin B1. Dose-dependent, sequence-specific, and gene-specific inhibition of
      both proteins was achieved at nanomolar concentrations of ONs in normal and
      breast cancer cells. Precise binding of the antisense ONs to their target RNA was
      absolutely required for antisense activity. Four or six base-mismatched ONs
      eliminated antisense activity confirming the sequence specificity of the
      antisense ONs. Antisense inhibition of p34cdc2 kinase resulted in a significant
      accumulation of cells in the Gap2/mitosis phase of the cell cycle in normal
      cells, but caused little effect on cell cycle progression in breast cancer cells.
      These data demonstrate the potency, specificity, and utility of C-5 propyne
      modified antisense ONs as biological tools and illustrate the redundancy of cell
      cycle protein function that can occur in cancer cells.

PMID- 9631069
TI  - Phage diabody repertoires for selection of large numbers of bispecific antibody
      fragments.
AB  - Methods for the generation of large numbers of different bispecific antibodies
      are presented. Cloning strategies are detailed to create repertoires of
      bispecific diabody molecules with variability on one or both of the antigen
      binding sites. This diabody format, when combined with the power of phage display
      technology, allows the generation and analysis of thousands of different
      bispecific molecules. Selection for binding presumably also selects for more
      stable diabodies. Phage diabody libraries enable screening or selection of the
      best combination bispecific molecule with regards to affinity of binding, epitope
      recognition and pairing before manufacture of the best candidate.

PMID- 9631070
TI  - Integration and expression of the high-molecular-weight glutenin subunit 1Ax1
      gene into wheat.
AB  - The unique bread-making characteristic of wheat flour is closely related to the
      elasticity and extensibility of the gluten proteins stored in the starchy
      endosperm, particularly the high-molecular-weight glutenin subunits (HMW-GS),
      which are important in determining gluten and dough elasticity. The quality of
      wheat cultivars depends on the number and composition of the HMW-GS present. We
      have introduced the HMW-GS 1Ax1 gene, known to be associated with good bread
      making quality, into the Bob White cultivar of wheat (Triticum aestivum L.), in
      which it is not present in nature, by the biolistic bombardment of cultured
      immature embryos. Of the 21 independent transformed lines selected, 20 expressed
      the selectable bar gene, and nine the 1Ax1 gene. The amount of HMW-GS 1Ax1
      protein produced in the different transgenic lines varied from 0.6% to 2.3% of
      the total protein, resulting in an increase of up to 71% in total HMW-GS
      proteins. The transgenic plants were normal, fertile, and showed Mendelian
      segregation of the transgenes. The accumulation of HMW-GS 1Ax1 was consistent and
      stable up to the R3 seed generation. These results demonstrate that it is
      possible to manipulate both the quantity and quality of HMW-GS, which influence
      the bread-making quality of wheat.

PMID- 9631071
TI  - A new paradigm for drug discovery in tropical rainforests.

PMID- 9631072
TI  - Abundance and competition in PCR.

PMID- 9631073
TI  - FBI forensics tries mtDNA.

PMID- 9631074
TI  - Another genome, another kingdom, another set of surprises.

PMID- 9631075
TI  - Ecogen Israel gets second approval.

PMID- 9631076
TI  - Mabs: a new lease on life for transplant patients?

PMID- 9631077
TI  - Making tolerance permanent.

PMID- 9631078
TI  - Can ReoPro repolish tarnished monoclonal therapeutics?

PMID- 9631079
TI  - Structure and fluorescence mechanism of GFP.

PMID- 9631080
TI  - Cellular probes on the move.

PMID- 9631081
TI  - Super hormones.

PMID- 9631082
TI  - Sleeping satellites: a risky prospect.

PMID- 9631083
TI  - Genetic tests for familial hypercholesterolemia.

PMID- 9631084
TI  - The specificity of protein aggregation [new; comment].

PMID- 9631085
TI  - Moving beyond the genome projects.

PMID- 9631086
TI  - Engineering antibody Fv fragments for cancer detection and therapy: disulfide
      stabilized Fv fragments.
AB  - Disulfide-stabilized Fv fragments of antibodies (dsFv) are molecules in which the
      VH-VL heterodimer is stabilized by an interchain disulfide bond engineered
      between structurally conserved framework positions distant from complementarity
      determining regions (CDRs). This method of stabilization is applicable for the
      stabilization of many antibody Fvs and has also been applied to a T-cell receptor
      Fv. A summary of the design strategy, and the construction and production of
      various dsFvs and dsFv-fusion proteins is presented. Included in the discussion
      are the biochemical features of dsFvs in comparison with scFvs, the effect of
      disulfide stabilization on Fv binding and activity, and various applications of
      dsFvs and dsFv-immunotoxins for tumor imaging and the treatment of solid tumors
      in animal models.

PMID- 9631087
TI  - The molecular structure of green fluorescent protein.
AB  - The crystal structure of recombinant wild-type green fluorescent protein (GFP)
      has been solved to a resolution of 1.9 A by multiwavelength anomalous dispersion
      phasing methods. The protein is in the shape of a cylinder, comprising 11 strands
      of beta-sheet with an alpha-helix inside and short helical segments on the ends
      of the cylinder. This motif, with beta-structure on the outside and alpha-helix
      on the inside, represents a new protein fold, which we have named the beta-can.
      Two protomers pack closely together to form a dimer in the crystal. The
      fluorophores are protected inside the cylinders, and their structures are
      consistent with the formation of aromatic systems made up of Tyr66 with reduction
      of its C alpha-C beta bond coupled with cyclization of the neighboring glycine
      and serine residues. The environment inside the cylinder explains the effects of
      many existing mutants of GFP and suggests specific side chains that could be
      modified to change the spectral properties of GFP. Furthermore, the
      identification of the dimer contacts may allow mutagenic control of the state of
      assembly of the protein.

PMID- 9631088
TI  - Spatial dynamics of GFP-tagged proteins investigated by local fluorescence
      enhancement.
AB  - We describe a method of monitoring the spatial dynamics of proteins in intact
      cells by locally enhancing the blue excited fluorescence of green fluorescent
      protein (GFP) using a spatially focused ultraviolet-laser pulse. GFP fusion
      proteins were efficiently expressed by micro-electroporation of in vitro
      synthesized mRNA into adherent mammalian cells. We found that the diffusion
      coefficient of cycle 3 mutant GFP was 43 microns2/sec, compared to 4 microns2/sec
      for wild-type GFP, suggesting that cycle 3 GFP diffuses freely in mammalian cells
      and is ideally suited as a fusion tag. The local fluorescence enhancement method
      was used to study the membrane dissociation rate of GFP-tagged K-ras, a small GTP
      binding protein that localizes to plasma membranes by a farnesyl lipid group and
      a polybasic region. Our data suggest that K-ras exists in a dynamic equilibrium
      and rapidly switches between a plasma membrane bound form and a cytosolic form
      with a plasma membrane dissociation time constant of 1.5 sec.

PMID- 9631089
TI  - Engineering human glycoprotein hormone superactive analogues.
AB  - We report the generation of superactive analogues of human glycoprotein hormones,
      with potential applications in thyroid and reproductive disorders. Current
      biological and structural data were used to rationalize mutagenesis. The 11-20
      region in the alpha-subunit with a cluster of lysine residues forms a previously
      unrecognized domain critical for receptor binding and signal transduction, as
      well as an important motif in the evolution of glycoprotein hormone activities.
      The gradual elimination of basic residues in the alpha-subunit coincided with the
      evolutionary divergence of the hominids from the Old World monkeys. By selective
      reconstitution of certain critical residues present in homologous nonhuman
      hormones we have developed human thyroid stimulating hormone and chorionic
      gonadotropin analogues with substantial increases in receptor binding affinity
      and bioactivity, thus providing a paradigm for the design of novel therapeutic
      protein analogues.

PMID- 9631090
TI  - Spontaneous change of a benign satellite RNA of cucumber mosaic virus to a
      pathogenic variant.
AB  - Plant satellite RNAs generally reduce the level of helper virus accumulation and
      attenuate the disease symptoms induced by the helper virus that they depend upon
      for replication and packaging. As such, satellite RNAs could be used as
      biocontrol agents to reduce the level of disease in field crops, either by the
      application of a viral vaccine to healthy plants, or by the transgenic expression
      of satellite RNA in transformed plants. One such virus/satellite RNA system
      already under use in field tests is cucumber mosaic virus (CMV) and its satellite
      RNAs. However, in this system, some satellite RNAs also intensify viral disease
      in particular host plants. We passaged a satellite RNA of CMV with its helper
      virus to determine whether a satellite RNA that attenuates CMV-induced disease on
      tobacco plants could mutate to a pathogenic form, which might then be selected.
      In several experiments involving strains of CMV from each of the two subgroups,
      the satellite rapidly mutated to a pathogenic form, which was selected. This
      demonstrates an inherent risk associated with the use of attenuating satellite
      RNAs as a form of biocontrol of CMV.

PMID- 9631091
TI  - Stability of food allergens to digestion in vitro.
AB  - An integral part of the safety assessment of genetically modified plants is
      consideration of possible human health effects, especially food allergy.
      Prospective testing for allergenicity of proteins obtained from sources with no
      prior history of causing allergy has been difficult because of the absence of
      valid methods and models. Food allergens may share physicochemical properties
      that distinguish them from nonallergens, properties that may be used as a tool to
      predict the inherent allergenicity of proteins newly introduced into the food
      supply by genetic engineering. One candidate property is stability to digestion.
      We have systematically evaluated the stability of food allergens that are active
      via the gastrointestinal tract in a simple model of gastric digestion,
      emphasizing the major allergens of plant-derived foods such as legumes (peanuts
      and soybean). Important food allergens were stable to digestion in the gastric
      model (simulated gastric fluid). For example, soybean beta-conglycinin was stable
      for 60 min. In contrast, nonallergenic food proteins, such as spinach ribulose
      bis-phosphate carboxylase/oxygenase, were digested in simulated gastric fluid
      within 15 sec. The data are consistent with the hypothesis that food allergens
      must exhibit sufficient gastric stability to reach the intestinal mucosa where
      absorption and sensitization (development of atopy) can occur. Thus, the
      stability to digestion is a significant and valid parameter that distinguishes
      food allergens from nonallergens.

PMID- 9631092
TI  - The similarities of bar and pat gene products make them equally applicable for
      plant engineers.
AB  - The bar and pat genes, isolated from different Streptomyces species, both encode
      a phosphinothricin acetyltransferase (PAT) and are widely applied in plant
      genetic engineering. The genes were expressed in Escherichia coli and the
      corresponding proteins were purified and used for functional and structural
      comparison. Both proteins are homodimers regardless of whether they are expressed
      in microorganisms or in plants. They have comparable molecular weights and show
      immuno-cross-reactivity to their respective polyclonal antisera. The enzymes have
      a similar substrate affinity towards L-phosphinothricin and do not acetylate any
      of the other L-amino acids tested. In model digestion experiments using simulated
      human gastric fluids, their enzymatic activity is decreased within seconds,
      accompanied by a rapid and complete breakdown of both proteins. These data
      demonstrate the structural and functional equivalence of the PAT proteins, which
      is also reflected in the comparable performance of transgenic plants carrying the
      bar or pat gene.

PMID- 9631093
TI  - Oligonucleotide ligation assay (OLA) for the diagnosis of familial
      hypercholesterolemia.
AB  - More than half of all deaths in Western society are related to arteriosclerotic
      cardiovascular diseases. Inherited disturbances in the low-density-lipoprotein
      (LDL) receptor and similar lipid-related defects account for the majority of
      these deaths. Testing procedures thus far rely on total cholesterol, LDL
      cholesterol, high-density-lipoprotein cholesterol, and triglyceride
      determinations. These tests are not able to provide any genetic information. We
      have developed an oligonucleotide ligation assay (OLA) that enables us to screen
      for high-risk individuals by testing for 19 common mutations in the LDL receptor
      and the apolipoprotein B genes using an automated genotyping-based two-step
      protocol. The novel OLA uses oligomeric pentaethyleneoxide mobility modifiers.
      The automated test will be useful in screening large populations for genetic data
      to distinguish relative from absolute risk, as well as for cost-effective
      familial analysis.

PMID- 9631094
TI  - Specific aggregation of partially folded polypeptide chains: the molecular basis
      of inclusion body composition.
AB  - During expression of many recombinant proteins, off-pathway association of
      partially folded intermediates into inclusion bodies competes with productive
      folding. A common assumption is that such aggregation reactions are nonspecific
      processes. The multimeric intermediates along the aggregation pathway have been
      identified for both the P22 tailspike and P22 coat protein. We show that for a
      mixture of proteins refolding in vitro, folding intermediates do not coaggregate
      with each other but only with themselves. This indicates that aggregation occurs
      by specific interaction of certain conformations of folding intermediates rather
      than by nonspecific coaggregation, providing a rationale for recovering
      relatively pure protein from the inclusion body state.

PMID- 9631095
TI  - Modifying the insect cell N-glycosylation pathway with immediate early
      baculovirus expression vectors.
AB  - The baculovirus-insect cell expression system is well-suited for recombinant
      glycoprotein production because baculovirus vectors can provide high levels of
      expression and insect cells can modify newly synthesized proteins in eucaryotic
      fashion. However, the N-glycosylation pathway of baculovirus-infected insect
      cells differs from the pathway found in higher eucaryotes, as indicated by the
      fact that glycoproteins produced in the baculovirus system typically lack complex
      biantennary N-linked oligosaccharide side chains containing penultimate galactose
      and terminal sialic acid residues. We recently developed a new type of
      baculovirus vector that can express foreign genes immediately after infection
      under the control of the viral ie1 promoter. These immediate early baculovirus
      expression vectors can be used to modify the insect cell N-glycosylation pathway
      and produce a foreign glycoprotein with more extensively processed N-linked
      oligosaccharides. These vectors can also be used to study the influence of the
      late steps in N-linked oligosaccharide processing on glycoprotein function.
      Further development could lead to baculovirus-insect cell expression systems that
      can produce recombinant glycoproteins with complex biantennary N-linked
      oligosaccharides structurally identical to those produced by higher eucaryotes.

PMID- 9631096
TI  - Housing conditions in a high density town near Harare, Zimbabwe.
AB  - OBJECTIVES: To determine the living conditions of people and to compare the
      results with census figures. DESIGN: Cross sectional. SETTING: A high density
      dormitory suburb of Harare, Zimbabwe. SUBJECTS: 108 stands containing 293
      households were surveyed in 1990 and 90 stands containing 454 households in 1993.
      MAIN OUTCOME MEASURE: Crowding index. RESULTS: An average increase of five people
      per stand in the three years to an average of 15 to 18 people on each stand was
      observed, allowing 16.4 to 19.6 m2 per person. Although the number of households
      living in one room increased from 101 (48.6%) in 1990 to 243 (72.5%) in 1993, the
      actual number of people per room did not increase. The Chitungwiza population was
      older than the overall population in Zimbabwe with an increased proportion of men
      of working age. About one tenth (10.8%) of heads of households who were resident
      for more than 20 years were still lodgers and 77.0% of these heads of households
      maintained that they still had a rural home. About three quarters (76.4%) of
      households had no kitchen and 74.1% of all households cooked on paraffin stoves
      or occasionally wood fires. CONCLUSION: Many new rooms had been built on the
      stands leading to overcrowding with possible implications for health.

PMID- 9631097
TI  - Contamination of traditional drinking water sources during a period of extreme
      drought in the Zvimba communal lands, Zimbabwe.
AB  - OBJECTIVES: Diarrhoeal disease is a significant public health concern in
      Zimbabwe, particularly for the population living in rural settings. The present
      study was undertaken to investigate the quality of water in a rural area of
      Zimbabwe during a period of extreme drought. DESIGN AND SETTING: A cross
      sectional survey study design was used. During the month of July 1995, water
      samples were collected from various actively used sources in the Zvimba communal
      lands, Zimbabwe. MAIN OUTCOME MEASURES: The level of contamination was estimated
      by use of the membrane filtration technique to detect the presence of Escherichia
      coli. RESULTS: Mean concentrations of E. coli found in boreholes and piped water
      were 9.3 and zero colonies per 100 ml, respectively. Using standardized criteria
      to define suitable drinking water quality, borehole and piped sources were
      determined to be more likely to provide satisfactory drinking water. CONCLUSIONS:
      Water samples collected from semi-protected and unprotected wells, which serve
      the majority of the population in the study area, were found to be unsatisfactory
      for drinking (range from two to 1,960 colonies of E. coli per 100 ml). Included
      are suggestions on how to efficiently utilize available water.

PMID- 9631098
TI  - Predictors of smoking in a cross section of novice mine workers.
AB  - OBJECTIVE: To determine demographic predictors of smoking status amongst novice
      mine workers. SETTING: Prospective mine workers undergoing fitness examination at
      the Medical Bureau for Occupational Diseases. DESIGN: Cross sectional study. MAIN
      OUTCOME MEASURES: Current smoking status. RESULTS: Smoking status is
      significantly linked to age, race group, nationality and previous employment
      status. Education is also a predictor of smoking status, but the association is
      weak. Smoking prevalence in subgroups of novice mine workers varies from less
      than 10% to nearly 75%. CONCLUSION: Assumptions of very high smoking rates
      amongst all mine workers are too simplistic. Smoking cannot be regarded globally
      as a major confounder of occupational exposure and occupational lung disease for
      all groups of mine workers.

PMID- 9631099
TI  - Anaemia, macrocytosis, vitamin B12 and folate levels in elderly Zimbabweans.
AB  - OBJECTIVES: To establish the ranges of full blood count (FBC), vitamin B12 and
      folate levels and to determine the prevalence of occult haematological
      abnormalities in older Zimbabweans. STUDY DESIGN: Community based cross sectional
      survey. SUBJECTS: 278 randomly selected healthy Zimbabweans aged > 65 years.
      INTERVENTIONS/STUDY FACTORS: Haemoglobin level, MCV, folate, B12 alcohol
      consumption. RESULTS: The median Hb was males 14.0 (range 8 to 18.3), females
      13.1 g/dl (7.9 to 18.1). 23% were anaemic (Hb < 13 g/dl in males, < 12 g/dl in
      females), 3% with microcytic and 20% with macrocytic indices. Overall 13% had low
      vitamin B12 and 30% had low folate levels. Folate levels were significantly lower
      in urban subjects and B12 levels were significantly lower in rural subjects.
      Fifty four subjects (21%) had an MCV > 100 fl. In this group, low folate levels
      were found in 22, low B12 levels in nine, excessive alcohol in eight and two
      subjects had elevated TSH. The MCV was higher in urban subjects. CONCLUSIONS:
      This study has revealed a large amount of occult haematological abnormality and
      interesting differences between rural and urban subjects. It focuses attention on
      low levels of folate, which should be preventable by simple nutritional
      education, as an extensive problem in the community.

PMID- 9631100
TI  - Primary cerebral lymphoma in Zimbabwe: a report of three patients.
AB  - Primary central nervous system lymphoma (PCNSL) is steadily increasing.
      Immunosuppressed individuals are at particular risk. In AIDS patients a clinical
      diagnosis of PCNSL is made in 0.5 to 8.4%, and a post mortem diagnosis in up to
      11% of cases. In spite of the extensive HIV epidemic in parts of Africa, a
      literature search revealed only one African report of this condition. The reasons
      for this apparent infrequency are not clear. Possibilities include under
      diagnosis or early demise of patients due to other AIDS related illnesses of
      earlier onset. Three patients with primary cerebral lymphoma from Zimbabwe are
      presented. All were young, with tumours of high grade showing typical features.

PMID- 9631101
TI  - Management of childhood splenic trauma--the Jos experience.
AB  - We studied retrospectively 22 children who were managed for splenic injuries at
      Jos University Teaching Hospital between September 1988 and October 1995. Sixteen
      were males and six were females (M:F = 2.7:1) with their ages between five and 15
      years and a mean of 10.3 years. Eleven were knocked down by vehicles while
      crossing the freeway, playing or hawking goods; seven fell from slippery mango
      trees after a downpour of rain while two were passengers in a vehicle that was
      involved in a head-on collision and another two were kicked in the abdomen as a
      result of assault. All had surgery. Four sustained Uphadhyaya and Simpson's Type
      1 injuries while six sustained Type IV injuries. Twelve had total splenectomy,
      seven had total splenectomy with heterotopic autotransplantation of splenic
      wafers while three had splenorrhaphy augmented with omentoplasty. An average of
      1.5 units of blood per patient were transfused. There was only one death.
      Considering that the majority (18) of these children sustained their splenic
      injuries while crossing the freeway (playing or hawking goods) and from falls
      from mango trees after the rains, we believe that there are preventable causes.
      Mandatory primary and junior secondary school education as well as legislature
      against child labour will help keep these children safe out of harm's way and
      thus drastically reduce the incidence of childhood splenic injuries in our
      environment.

PMID- 9631102
TI  - Tuberculosis and iron overload in Africa: a review.
AB  - Both pulmonary tuberculosis and dietary iron overload are common conditions in
      sub-Saharan Africa. The incidence of tuberculosis has increased markedly over the
      last decade, primarily as a result of the rapid spread of infection with the
      human immunodeficiency virus (HIV). Dietary iron overload affects up to 10% of
      adults in rural populations and is characterized by heavy iron deposition both in
      parenchymal cells and in macrophages. Mycobacterium tuberculosis grows within
      macrophages and, at the same time, the antimicrobial function of macrophages is
      important in the body's defence against tuberculosis. In vitro, the loading of
      macrophages with iron reduces the response of these cells to activation by
      interferon-gamma and diminishes their toxicity against micro-organisms. In the
      clinical setting, dietary iron overload appears to increase the risk for death
      from tuberculosis even in the absence of the acquired immunodeficiency syndrome.
      The combination of dietary iron overload and infection with the HIV, with
      impaired function of both macrophages and T-cells, may make patients especially
      vulnerable to tuberculosis. It is possible that the prevention and treatment of
      dietary iron overload could contribute to the control of tuberculosis in African
      populations.

PMID- 9631103
TI  - Missed diagnosis--adenomatous polyposis coli.

PMID- 9631104
TI  - The sensate deep inferior epigastric musculocutaneous flap: details of the
      operative technique.

PMID- 9631105
TI  - Health status of the children in a high density town near Harare, Zimbabwe.
AB  - OBJECTIVES: To determine the health status of the children for conditions
      associated with poverty. DESIGN: Cross sectional. SETTING: Households in
      Chitungwiza, a dormitory town of Harare, Zimbabwe. SUBJECTS: 181 children less
      than five years of age in 1990 and 162 in 1993. MAIN OUTCOME MEASURES:
      Nutritional status and illness experienced by children. RESULTS: A total of 191
      (90.0%) mothers breast fed for more than a year. Thirty two (24.2%) children more
      than six months old in 1990 and 24 (18.9%) in 1993 were offered less than three
      meals a day. Illnesses were most common (90.9%) in children aged six to 11 months
      old and decreased after this. Diarrhoea and coughs accounted for most of this
      excess (87.9%). Coughs alone affected 33.8% of children of all ages. Knowledge of
      making rehydration sugar/salt solution was wrong in 23.9% of mothers. Appropriate
      immunization was given to 85% of children in 1993. Twenty one (14.9%) children in
      1990 and 15(12.2%) in 1993 were under 80% weight for age. Thirteen (8.7%)
      children in 1990 and 16 (10.8%) in 1993 were stunted. CONCLUSION: Breast feeding
      was generally satisfactory but the number of meals offered to a fifth of the
      children aged more than six months was inadequate. Instructions for making
      rehydration sugar/salt solution, on composition and quantity to be given should
      be made easily available so that the rate of mothers with wrong knowledge of
      making the sugar salt solution could be decreased. Children of age six to 11
      months need to be kept warm to avoid coughs and need to be brought up in hygienic
      conditions to avoid diarrhoea.

PMID- 9631106
TI  - Challenges posed by changes in measles transmission patterns.
AB  - OBJECTIVE: To quantify changes in measles transmission patterns. DESIGN: Analysis
      of measles surveillance data. SUBJECTS: All measles cases identified in 1988.
      MAIN OUTCOME MEASURES: Proportion of cases in age group 60 to 119 months,
      proportions of vaccinated and unvaccinated cases in age group 60 to 119 months,
      and occurrence of cases in schools. RESULTS: Measles vaccination coverage was
      91%. Incidence rate of measles was 205 per 100,000 population. The age group 60
      to 119 months accounted for 49% of all reported cases and 68% of cases in this
      age group were vaccinated. There were measles epidemics in schools and these were
      associated with occurrence of secondary cases in younger siblings in the
      community. Case fatality rate and mortality rate were 0.4% and one per 100,000
      population respectively. CONCLUSION: High measles transmission in children of
      school going age could spill into the community through generation of secondary
      cases among younger siblings and this could result in high morbidity and
      mortality in this vulnerable group. It is recommended that either revaccination
      at school entry or mass vaccination campaigns be carried out in affected age
      groups at schools to reduce occurrence of epidemics.

PMID- 9631107
TI  - The surgical pathology of the appendix in South African blacks.
AB  - OBJECTIVE: The aim of this study was to evaluate the type of pathology seen in
      appendices removed for acute appendicitis. DESIGN: A retrospective study.
      SETTINGS: Department of Anatomical Pathology at Ga-Rankuwa/Medunsa Academic
      Complex, Gauteng Province, South Africa. SUBJECTS: 408 Black patients who had
      appendectomy at Garankuwa Hospital. MAIN OUTCOME MEASURES: Prevalence of
      appendicitis. RESULTS: Appendicitis was diagnosed in 65.7% of the cases of which
      25% showed perforation. The disease was common in males and was predominantly
      seen in the second decade. Parasites were seen in 3.4% of cases and two benign
      tumours were seen. CONCLUSION: Appendicitis is common amongst urban South African
      Blacks and the pattern of the disease is similar to that observed in other
      African urban centres.

PMID- 9631108
TI  - Acute bacterial meningitis in a developing country: diagnosis related mortality
      among paediatric patients.
AB  - OBJECTIVES: To evaluate the effect of late diagnosis and other factors on outcome
      of paediatric bacterial meningitis (BM) and recommend appropriate intervention.
      DESIGN: Case series. SETTING: University of Calabar Teaching Hospital, Calabar,
      Nigeria. SUBJECTS: 62 consecutive BM patients aged two months to 16 years
      admitted between 1991 and 1994. MAIN OUTCOME MEASURES: Mortality rate. RESULTS:
      Diagnostic difficulties experienced in 58% of cases and other factors resulted in
      delayed diagnosis and high mortality (20 to 47%). CONCLUSION: Only elimination of
      the identified inadequacies in management can significantly reduce the BM-related
      high mortality in developing countries.

PMID- 9631110
TI  - Scabies: revisit in a depressed economy.
AB  - Scabies is a highly contagious disease of the skin caused by an ectoparasite
      arthropod called Sarcoptes scabiei var hominis. It has a world-wide distribution
      and affects all ages with no specific gender predisposition. Scabies is of public
      health interest because certain environment factors such as overcrowding, poor
      hygiene, delayed treatment of primary cases and lack of public enlightenment are
      conducive to its spread. However, prompt and adequate therapy is rewarding and
      prevents spread.

PMID- 9631109
TI  - Foreign body causing chronic subacute small bowel obstruction: an unusual case
      from Harare Hospital.
AB  - This report describes the clinical presentation, diagnostic work up and surgical
      management of a rare case of a wedge-shaped organic foreign body found lodged
      transversely in the wall of the terminal ileum at laparotomy in a 74 year old
      woman operated on for segmental constrictive intestinal obstruction. The presence
      of foreign bodies in the gastro-intestinal tract as causative agents of
      intestinal obstruction is discussed.

PMID- 9631111
TI  - A randomised crossover comparison of reserpine and sustained-release nifedipine
      in hypertension.
AB  - OBJECTIVE: To compare the effectiveness of the combination of hydrochlorothiazide
      (HCT) plus sustained-release nifedipine with the combination of HCT plus
      reserpine in lowering high blood pressure (BP) unresponsive to HCT monotherapy.
      DESIGN: An open, randomised crossover drug trial. SETTING: Outpatients' clinic in
      Parirenyatwa Hospital, Harare, a tertiary referral centre. SUBJECTS: 32 Black
      patients of both sexes with newly diagnosed or previously treated hypertension
      aged between 21 and 65 years who had a BP > 140/95 after receiving HCT 25 mg
      daily for four weeks were studied. INTERVENTION: Patients were kept on HCT 25 mg
      daily and were randomised to receive either reserpine 0.25 mg daily or nifedipine
      (Adalat Retard) 20 mg bd for four weeks. This was followed by a two week washout
      period during which patients received HCT 25 mg daily only. After the washout
      period patients were crossed over to the alternative treatment for four weeks.
      Patients were kept on HCT 25 mg daily throughout the trial. MAIN OUTCOME
      MEASURES: The main outcome measure was the fall in BP which was taken as the
      difference between the BP at baseline and the BP at the end of each treatment
      period. Both systolic blood pressure (SBP) and diastolic blood pressure (DBP)
      measurements were taken. RESULTS: Both second line drugs were effective in
      lowering SBP and DBP and there was no significant difference between them.
      Nifedipine reduced SBP by 18.9 mmHg (95% CI 12.1 to 25.7) and DBP by 9.6 mmHg
      (95% CI 7.2 to 12.0). Reserpine reduced SBP by 15.9 mmHg (95% CI 8.4 to 23.4) and
      DBP by 11.1 mmHg (95% CI 7.5 to 14.6). However, only two patients attained the
      target DBP of < or = 90 mmHg after each active treatment period. CONCLUSION AND
      RECOMMENDATIONS: Since both agents were equally effective in reducing both SBP
      and DBP and reserpine is much cheaper than nifedipine, it is recommended that for
      a developing country like Zimbabwe, the combination of HCT and reserpine at the
      above doses should be used as the first step to treat mild to moderate
      hypertension without evidence of end organ damage. However, further trials should
      compare BP lowering effects as well as end organ protection offered by the trial
      drugs.

PMID- 9631112
TI  - Risk factors for HIV infection in a rural cohort in Zimbabwe: a pilot study.
AB  - OBJECTIVE: To identify demographic, sexual behavioural and cultural risk factors
      for human immunodeficiency virus (HIV) infection in a rural community in
      Zimbabwe. DESIGN: Prospective study. SETTING: Rural area in Zimbabwe. SUBJECTS:
      207 subjects (81 males, 126 females) mean age 31.6 years (SD 15.3), range 12 to
      76 years living in the area. MAIN OUTCOME MEASURES: HIV seropositivity and
      seroconversion, exposure or no exposure to risk factor. RESULTS: Prevalence of
      HIV was 7.7% and was associated with being divorced or widowed [Odds ratio (OR)
      4.26, 95% confidence interval (CI) 1.17 to 14.97] and past history of sexually
      transmitted diseases (STDs) [(OR 3.54, 95% CI 1.31 to 9.89)]. Seroconversion rate
      was 3.6% per year and was associated with history of STD [Relative Risk (RR)
      13.22, 95% CI 1.15 to 156.1)] during the follow up period. Individuals over 20
      years of age, those reporting one or more sexual partners, those reporting
      irregular use of condoms and those scarified were at greater risk than their
      counterparts. Individuals who reported being circumcised were at slightly lesser
      risk than those who did not report circumcision. CONCLUSION: STDs were major
      determinants of HIV transmission in the study area. In addition being divorced or
      widowed was a risk factor for HIV infection. Scarification, tattooing and
      circumcision require further investigations.

PMID- 9631113
TI  - Diagnosis of sickle-cell disease by DNA analysis in Nigeria.
AB  - OBJECTIVE: To compare genotyping of leucocyte DNA by PCR and Dde I with the
      conventional genotyping of haemoglobin of the same subject. DESIGN: Comparative
      study. SUBJECTS: 25 adults, 16 males and nine females. MAIN OUTCOME MEASURES:
      Predictability. RESULTS: In all cases the results were comparable. CONCLUSIONS:
      The technology can be applied locally to prenatal diagnosis of sickle-cell
      disease by chorionic sampling and, therefore, improve the management of sickle
      cell disease in Nigeria.

PMID- 9631114
TI  - TNM classification and breast cancer in an African population: a descriptive
      study.
AB  - OBJECTIVE: To determine the stage of female breast cancer in an African
      population at presentation by using the TNM classification of the International
      Union Contra Cancer (UICC). DESIGN: A descriptive study. SETTING: Hospital based
      investigation. SUBJECTS: All 50 female patients with breast carcinoma admitted
      between March and October 1996 to the surgery wards at the Muhimbili Medical
      Centre, the largest referral centre in Tanzania were studied for the stage of the
      disease at presentation. RESULTS: A total of 50 cases were recruited in this
      study. There was not a single case in Stage I. In Stage II there was only one
      case (T2 N0, n = 1). There were seven cases in Stage IIIA (T3 N0, n = 5; T1 N2, n
      = 1; T3 N2, n = 1) while in Stage IIIB there were 37 cases (T3 N3, n = 1; T4 N1,
      n = 27; T4 N2, n = 9). There were five cases in Stage IV (M1, n = 5).
      Histological analysis revealed all tumours were infiltrating duct carcinoma.
      Metastatic disease (Stage IV) was observed only in patients aged above 50 years.
      CONCLUSIONS: Breast cancer presents predominantly as a locally advanced disease,
      with virtual absence of early disease. A majority of the patients are
      premenopausal in an African population. Self breast examination (SBE) including
      other strategies suggested earlier are recommended to aid in early detection of
      breast cancer.

PMID- 9631115
TI  - Distribution of median nerve to muscles of the anterior compartment of the arm.
AB  - Distribution of the median nerve in the arm is not normally subjected to
      variation. This report represents a case of complete absence of the
      musculocutaneous nerve from the lateral cord of the brachial plexus. The
      innervation of the muscles of the anterior (flexor) compartment of the arm was by
      direct branches from the median nerve. This variation was present in both the
      right and left limbs.

PMID- 9631116
TI  - Interventions to reduce mother to child transmission of HIV.

PMID- 9631117
TI  - Blood pressure measurement and assessment of the hypertensive patient.

PMID- 9631119
TI  - The Society of Behavioral Medicine--18th annual meeting. San Francisco,
      California, USA. April 16-19, 1997. Abstracts.

PMID- 9631118
TI  - 13th Scientific meeting of the American Society of Hypertension. May 13-16, 1998.
      Abstracts.

PMID- 9631120
TI  - 11th International Conference on Antiviral Research. San Diego, California, USA.
      April 5-10, 1998. Abstracts.

PMID- 9631121
TI  - Extramural Grant Program 1997. Chicago, Illinois, USA. June 10-11, 1997.
      Abstracts.

PMID- 9631122
TI  - 24th Annual meeting of the European Group for Blood and Bone Marrow
      Transplantation and 14th meeting of the Nurses Group. Courmayeur, Italy. March 22
      26, 1998. Abstracts.

PMID- 9631123
TI  - Proceedings of the British Pharmacological Society meeting. 10-12 December 1997.
      Abstracts.

PMID- 9631124
TI  - [Diabetes. Marrakech 98. 24-27 March 1998. Abstracts].

PMID- 9631125
TI  - 22nd Annual meeting of the German Society for Cell Biology. Saarbrucken, March 15
      19, 1998. Abstracts.

PMID- 9631126
TI  - The 71st annual meeting of the Japanese Pharmacological Society. Kyoto, Japan,
      March 23-26, 1998. Abstracts.

PMID- 9631127
TI  - 4th International Symposium on Hodgkin's Lymphoma. Koln, Germany, March 28-April
      1, 1998. Abstracts.

PMID- 9631128
TI  - [Therapy of mild to medium degree depression].

PMID- 9631129
TI  - [Diagnosis and therapy of stroke].

PMID- 9631131
TI  - 66th Annual meeting of the Swiss Society of Internal Medicine, the annual meeting
      of the Swiss Society of Hematology, the Swiss Society of Endocrinology and
      Diabetes. Lausanne, 7-9 May 1998. Abstracts.

PMID- 9631130
TI  - German Pharmaceutical Society European Graduate Student meeting. Frankfurt/Main,
      Germany, 20-22 February 1998. Abstracts.

PMID- 9631132
TI  - Interleukin-2 inhibits HIV-1 replication in human macrophages by modulating
      expression of CD4 and CC-chemokine receptor-5.
AB  - OBJECTIVE: To determine the effect of recombinant human interleukin (IL)-2 on HIV
      1 replication and macrophage colony stimulating factor (M-CSF) production by HIV
      1-infected monocyte-derived macrophages (MDM). DESIGN: Therapeutic use of IL-2
      increases the number and function of CD4+ T cells. IL-2 also increases M-CSF
      production and M-CSF receptor expression by human monocytes, but the subsequent
      effects on HIV-1 replication in MDM have yet to be determined. MDM from HIV-1
      seronegative donors were cultured in the presence and absence of IL-2 and
      infected with HIV-1. Harvested supernatants were monitored for reverse
      transcriptase activity and M-CSF production. RESULTS: Reverse transcriptase
      activity was significantly lower when MDM cultures were treated with IL-2 for 10
      days prior to infection with HIV-1. IL-2 did not stimulate production of
      inhibitory chemokines or cytokines, but FACS analysis revealed that expression of
      CD4, the primary HIV-1 receptor, and CC-chemokine receptor-5, a coreceptor used
      by macrophage-tropic viruses, are down modulated after treatment with IL-2.
      CONCLUSION: IL-2 may not only be of benefit in restoring immune function in AIDS
      patients, but may also help to prevent the infection of healthy macrophages by
      decreasing their expression of HIV-1 receptors.

PMID- 9631133
TI  - Highly active antiretroviral treatment in HIV infection: benefits for
      neuropsychological function.
AB  - OBJECTIVES: To determine whether highly active antiretroviral therapy (HAART) is
      associated with reduced HIV-associated neuropsychological impairment. DESIGN:
      Cross-sectional analysis in a natural history study of adaptation to HIV/AIDS.
      METHOD: A sample of 130 homo-/bisexual men with HIV/AIDS (mean age, 41 years; 42%
      non-white) were evaluated with a neuropsychological battery assessing attention,
      concentration, psychomotor speed, learning, memory and executive function.
      Subjects taking HAART were compared with those not taking HAART on demographics,
      CD4 cell count, viral load, scores on individual neuropsychological tests and
      proportion with neuropsychological impairment. RESULTS: Sixty-nine (53%) subjects
      were taking HAART, and 48 (37%) were neuropsychologically impaired. Subjects
      taking HAART had lower mean CD4 cell counts than those not taking HAART (254
      versus 342 x 10(6)/l; P < 0.05), although they were more likely to have
      undetectable viral load (42 versus 20%; P < 0.01) and were less likely to be
      neuropsychologically impaired (22 versus 54%; P < 0.0001). Subjects taking HAART
      performed significantly better on tests of attention, concentration, learning,
      memory, and psychomotor speed. After excluding subjects with potential non-HIV
      confounders of neuropsychological function, those without neuropsychological
      impairment had significantly lower mean viral load levels and were more likely to
      have undetectable viral load than those with impairment. CONCLUSION: These
      preliminary findings suggest that HAART benefits neuropsychological function
      through the reduction of viral load.

PMID- 9631135
TI  - Mechanisms and timing of mother-to-child transmission of HIV-1.

PMID- 9631134
TI  - A placebo-controlled trial of didanosine plus stavudine, with and without
      hydroxyurea, for HIV infection. The Swiss HIV Cohort Study.
AB  - OBJECTIVE: To explore the short-term effects on surrogate markers for HIV
      progression of didanosine (ddl) plus stavudine (d4T), with or without
      hydroxyurea. DESIGN: Randomized, double-blinded, prospective study. SETTING:
      Swiss HIV Cohort Study. PATIENTS: A total of 144 patients (75% antiretroviral
      naive) were studied (mean baseline HIV-1 RNA, 4.53 log10 copies/ml; mean CD4 cell
      count, 370 x 10(6)/l). INTERVENTION: Patients received ddl (200 mg twice daily)
      plus d4T (40 mg twice daily), with additional hydroxyurea (500 mg twice daily) or
      placebo. MAIN OUTCOME MEASURES: The primary endpoint was a reduction of viraemia
      below 200 copies/ml after 12 weeks. At that time, patients who did not reach the
      primary endpoint were withdrawn in the hydroxyurea arm, whereas patients in the
      placebo group had the option of adding hydroxyurea to ddl and d4T. All patients
      were followed until week 24. RESULTS: After 12 weeks, 54% of the patients
      randomized to hydroxyurea had viraemia below 200 copies/ml, compared with 28% on
      placebo (P < 0.001). Using an ultrasensitive assay with a limit of detection of
      20 copies/ml, 19% of patients receiving hydroxyurea had viraemia levels below 20
      copies/ml, compared with 8% on placebo (P = 0.05). Mean decrease in HIV-1 RNA was
      2.3 and 1.7 log10 copies/ml for hydroxyurea and placebo groups, respectively (P =
      0.001). Hydroxyurea was found to induce lymphopenia (-124 x 10(6)/l). Increase in
      CD4 cell counts was +28 x 10(6)/l during hydroxyurea treatment compared with +107
      x 10(6)/l on placebo (P = 0.001). CONCLUSIONS: Hydroxyurea improved the antiviral
      activity of d4T and ddl over a 12-week period, but was associated with a smaller
      increase in CD4 cell counts due to hydroxyurea-induced lymphopenia.

PMID- 9631136
TI  - Characterization of the viral population during primary HIV-1 infection.
AB  - OBJECTIVE: To study viral heterogeneity at a very early phase of primary HIV-1
      infection. DESIGN: Samples were drawn very early during primary HIV-1 infection.
      A virus population-based approach was used to study the viral heterogeneity in
      the C2-V3 and p17 regions. METHODS: Plasma samples (n = 33) were obtained before
      or shortly after onset of acute symptoms in 15 patients. In all subjects, the
      first sample was drawn within 10 days after onset of symptoms. Peripheral blood
      mononuclear cells (PBMC) were available in two patients. The number of
      polymorphic sites in the C2-V3 (15 patients) and p17 regions (eight patients)
      were determined by direct sequencing. RESULTS: The sequence heterogeneity was
      restricted in most patients, although only two out of 15 patients had a
      completely homogeneous C2-V3 sequence. However, pronounced individual differences
      were seen. Rapid sequence changes occurred during the first month in two
      patients. In one patient, the major DNA species at day 12 later became the major
      species in plasma. CONCLUSIONS: The viral population is seldom completely
      homogeneous during primary HIV-1 infection, although the heterogeneity is
      restricted in most, but not all, patients. These individual differences do not
      seem to be due to sex or viral subtype. Rapid changes of the virus population may
      occur during primary HIV-1 infection. The DNA species detected in PBMC do not
      only represent earlier viral quasispecies but are also a potential source of
      future viral RNA species.

PMID- 9631137
TI  - Infection of baboons with a simian immunodeficiency virus/HIV-1 chimeric virus
      constructed with an HIV-1 Thai subtype E envelope.
AB  - OBJECTIVE: To construct an infectious chimeric simian immunodeficiency virus/HIV
      1 (SHIV) with the envelope of a Thai subtype E HIV-1 strain for use in a non
      human primate model. METHODS: A novel SHIV genome was derived using the sequences
      of the ectodomain of the envelope gene from the Thai subtype E strain, HIV
      1(9466). This SHIV (SHIV9466.33) was recovered by cocultivation from human
      peripheral blood mononuclear cells (PBMC) after transfection of human
      rhabdosarcoma cells. Rhesus macaque and baboon PBMC were screened in vitro for
      susceptibility to infection with SHIV9466.33. After successful infection of
      baboon PBMC, four animals were inoculated intravenously with SHIV9466.33 and
      monitored for plasma viral RNA, virus isolation from the PBMC, seroconversion, T
      cell subsets, and signs of disease. RESULTS: SHIV9466.33 was able to infect PBMC
      from 12 out of 14 baboons. All four of the baboons selected for in vivo
      inoculation became infected. Peak plasma viral RNA levels of 8000 to 700,000 RNA
      copies/ml were measured at 2 weeks post-inoculation. Virus was isolated from the
      PBMC of all four baboons during acute infection, and all seroconverted. Although
      transient declines in CD4+ T-cells were observed during early infection, CD4+
      levels remained within normal ranges thereafter. In contrast, in vitro cultures
      of PBMC of four rhesus macaques were not susceptible to infection with
      SHIV9466.33. CONCLUSION: SHIV9466.33 containing an HIV-1 subtype E envelope
      displayed tropism for baboon PBMC but not for rhesus macaque PBMC. This chimeric
      virus established infection and induced antiviral antibodies in baboons
      inoculated by the intravenous route with cell-free virus. Thus, infection of
      baboons with SHIV9466.33 will serve as an important animal model for future
      studies of HIV-1 vaccine efficacy.

PMID- 9631138
TI  - In vitro selective elimination of HIV-infected cells from peripheral blood in
      AIDS patients by the immunotoxin DAB389CD4.
AB  - OBJECTIVES: To study the antiviral efficacy of the recombinant immunotoxin
      DAB389CD4 against wild-type strains of HIV and to analyse its potential toxicity
      in non-infected peripheral blood mononuclear cells (PBMC). DESIGN AND METHODS:
      PBMC from HIV-seropositive patients were cultured in the presence of DAB389CD4.
      After 30 days in culture, viral load was assessed by quantification of RNA levels
      in supernatants and HIV-specific polymerase chain reaction (PCR) was performed
      for measuring proviral DNA as an indicator of remaining virus in cells. To study
      the toxicity of DAB389CD4, PBMC from healthy donors were isolated and cell
      viability and lymphocyte proliferation were assessed after immunotoxin treatment.
      RESULTS: DAB389CD4 presented a strong antiviral activity in five of the six
      primary isolates decreasing p24 production in cultures to undetectable levels and
      eliminating selectively HIV-infected cells as measured by HIV DNA-specific PCR.
      One viral isolate was resistant to DAB389CD4 treatment. The immunotoxin was
      active against both syncytial and non-syncytial HIV strains. DAB389CD4 was not
      toxic in non-infected PBMC as measured by different techniques: trypan blue
      exclusion, methyl thiazol tetrazolium oxidation, lymphocyte proliferation, and
      CD4 cell count. CONCLUSIONS: DAB389CD4 showed a strong antiviral and specific
      activity against primary HIV isolates by killing selectively HIV-infected cells
      without affecting non-infected cells. This antiviral effect produced the
      eradication of HIV in cultures and indicated the potential use of this drug as a
      new therapeutic tool in combination with antiretroviral drugs. This immunotoxin
      would be especially interesting in the context of the marginal populations of HIV
      infected cells remaining after successful antiviral treatment.

PMID- 9631139
TI  - Suppression of HIV-1 infection in linomide-treated SCID-hu-PBL mice.
AB  - BACKGROUND: Proinflammatory cytokine overproduction, as well as synthesis of the
      inducible form of nitric oxide synthase (iNOS), are known to play a major role in
      HIV-1-triggered disease. AIDS patients show increased serum tumour necrosis
      factor (TNF)-alpha and interferon (IFN)-gamma levels, which synergize with HIV-1
      produced nitric oxide (NO) to augment viral replication. Linomide has strong
      immunomodulatory effects in animals and humans, yielding promising clinical
      benefits in several pathological disorders including septic shock and autoimmune
      disease, processes largely mediated by overproduction of these cytokines. In
      peripheral T cells, linomide also prevents apoptosis triggered by a variety of
      stimuli, including superantigens, dexamethasone and vaccinia virus. DESIGN AND
      METHODS: Linomide inhibits production of proinflammatory cytokines such as TNF
      alpha, interleukin-1 beta and IFN-gamma, as well as iNOS synthesis. The SCID-hu
      PBL mouse model was used to analyse the effect of linomide on HIV-1 infection. T
      cell frequency was characterized in reconstituted animals, and the frequency of
      infected mice and viral load of infected animals were studied. RESULTS: Linomide
      promotes an increase in human CD4+ T-cell counts in the peritoneal cavity of HIV
      1-infected, linomide-treated mice. Linomide also prevents human TNF-alpha and IFN
      gamma production, as well as iNOS expression and affects the viral load,
      promoting potent suppression of HIV-1 infectivity as detected in peritoneal
      cavity and spleen. CONCLUSIONS: The combination of linomide's properties, namely,
      blockage of proinflammatory cytokine and NO production, as well as prevention of
      apoptosis, is of paramount interest, making linomide a potential candidate for
      combating HIV-1 infection or preventing some of its associated pathological
      manifestations.

PMID- 9631140
TI  - Pneumocystis carinii mutations associated with sulfa and sulfone prophylaxis
      failures in AIDS patients.
AB  - BACKGROUND: Failures of prophylaxis against Pneumocystis carinii pneumonia (PCP)
      in AIDS patients do occur, but no evidence for drug resistance has yet been
      presented. OBJECTIVE: To determine whether mutations in the sulfa and sulfone
      drug target are associated with failure of prophylaxis using a sulfa-containing
      agent. METHODS: Portions of the gene for P. carinii dihydropteroate synthase
      (DHPS), the sulfa and sulfone target, from 27 patients (20 of whom had AIDS)
      diagnosed with PCP between 1976 and 1997 were amplified using polymerase chain
      reaction and sequenced. Seven of the 27 patients (all of whom had AIDS) were
      receiving sulfa or sulfone drugs as prophylaxis for PCP. RESULTS: Mutations were
      found at only two amino-acid positions and were significantly more common in
      patients who received sulfa/sulfone prophylaxis. Mutations were observed in five
      (71%) out of seven isolates from AIDS patients receiving sulfa/sulfone as
      prophylaxis compared with only two (15%) out of 13 specimens from AIDS patients
      who did not (P = 0.022). No mutations were seen in isolates from seven non-HIV
      infected patients, none of whom were on prophylaxis. Mutations were only observed
      in specimens obtained in 1995-1997. CONCLUSIONS: Mutations in two amino-acid
      positions were significantly more common in AIDS patients with PCP who failed
      sulfa/sulfone prophylaxis. These amino acids appeared to be directly involved in
      both substrate and sulfa binding, based on homology to the Escherichia coli DHPS
      crystal structure. Thus, the results were consistent with the possibility that
      mutations in the P. carinii DHPS are responsible for some of the failures of
      sulfa/sulfone prophylaxis in AIDS patients.

PMID- 9631141
TI  - No evidence for proliferation in the blood CD4+ T-cell pool during HIV-1
      infection and triple combination therapy.
AB  - OBJECTIVE: To evaluate the role of cell proliferation in peripheral blood
      lymphocyte (PBL) dynamics during HIV infection and potent antiretroviral therapy
      including protease inhibitors. DESIGN: Transverse study of 150 patients at
      different stages of infection. Longitudinal study of 50 patients on triple
      combination antiretroviral therapy with 9-month follow-up. METHODS: Ex vivo
      incubation of fresh PBL with the DNA biosynthetic marker bromodeoxyuridine
      (BrdU). Flow cytometric analysis of cell phenotypes and BrdU incorporation.
      Parallel determination of plasma virus load and CD4+ cell counts. RESULTS:
      Percentages of BrdU+ B and T lymphocytes found in patients with asymptomatic HIV
      infection were not different from the low values found in HIV-seronegative
      controls, and were not correlated with the CD4+ cell count. DNA synthesis
      increased significantly only during acute opportunistic infections occurring in
      patients with high plasma viral load and fewer than 100 x 10(6) CD4+ cells/l.
      Triple combination therapy induced a decrease of plasma virus load and a rise of
      CD4+ cell counts, whereas BrdU incorporation remained low or decreased.
      CONCLUSION: Proliferation of peripheral blood T cells observed at late stages of
      HIV infection corresponds to a response to opportunistic infections. Apart from
      these particular cases, proliferation in this compartment does not appear as a
      critical parameter of CD4+ cell kinetics during chronic HIV infection and potent
      therapy.

PMID- 9631142
TI  - Clinical predictors of Pneumocystis carinii pneumonia, bacterial pneumonia and
      tuberculosis in HIV-infected patients.
AB  - BACKGROUND: Clinicians are frequently faced with the differential diagnosis
      between Pneumocystis carinii pneumonia (PCP), bacterial pneumonia, and pulmonary
      tuberculosis in HIV-infected patients. OBJECTIVES: To identify features that
      could help differentiate these three pneumonia types at presentation by
      evaluating the clinical characteristics of the three diagnoses among patients at
      two urban teaching hospitals. DESIGN: Retrospective chart review. METHODS: Cases
      were HIV-infected patients with a verified hospital discharge diagnosis of PCP (n
      = 99), bacterial pneumonia (n = 94), or tuberculosis (n = 36). Admitting notes
      were reviewed in a standardized manner; univariate and multivariate analyses were
      used to determine clinical predictors of each diagnosis. RESULTS: Combinations of
      variables with the highest sensitivity, specificity, and odds ratios (OR) were as
      follows: for PCP, exertional dyspnea plus interstitial infiltrate (sensitivity
      58%, specificity 92%; OR, 16.3); for bacterial pneumonia, lobar infiltrate plus
      fever < or = 7 days duration (sensitivity 48%, specificity 94%; OR, 14.6); and
      for tuberculosis, cough > 7 days plus night sweats (sensitivity 33%, specificity
      86%; OR, 3.1). On regression analysis, independent predictors included
      interstitial infiltrate (OR, 10.2), exertional dyspnea (OR, 4.9), and oral thrush
      (OR, 2.9) for PCP; rhonchi on examination (OR, 12.4), a chart mention of 'toxic'
      appearance (OR, 9.1), fever < or = 7 days (OR, 6.6), and lobar infiltrate (OR,
      5.8) for bacterial pneumonia; and cavitary infiltrate (OR, 21.1), fever > 7 days
      (OR, 3.9), and weight loss (OR, 3.6) for tuberculosis. CONCLUSIONS: Simple
      clinical variables, all readily available at the time of hospital admission, can
      help to differentiate these common pneumonia syndromes in HIV-infected patients.
      These findings can help to inform clinical decision-making regarding choice of
      therapy, use of invasive diagnostic procedures, and need for respiratory
      isolation.

PMID- 9631143
TI  - Pilot study of the immunologic effects of recombinant human growth hormone and
      recombinant insulin-like growth factor in HIV-infected patients.
AB  - OBJECTIVE: To study the immunologic effects of recombinant human growth hormone
      (rhGH), recombinant human insulin-like growth factor type 1 (rhIGF-1), or the
      combination, in patients with moderately advanced HIV infection. DESIGN:
      Randomized but not blinded trial. SETTING: Government medical research center.
      PATIENTS: Twenty-four HIV-infected patients with CD4 cell counts of 100-400 x
      10(6)/l who were receiving nucleoside antiretroviral therapy. INTERVENTIONS:
      Either rhGH, rhIGF-1, or the combination was administered subcutaneously for 12
      weeks. MAIN OUTCOME MEASURES: Immunologic parameters, including T-cell subsets
      and assays of in vitro interleukin (IL)-2 production in response to antigens and
      mitogens, and safety profile. RESULTS: Plasma IGF-1 levels were low or low-normal
      prior to treatment and increased with all three therapies. There were no
      significant changes in CD4 cell counts, RA/RO CD4 cell subsets, natural killer
      cell function, immunoglobulin levels, or in vitro IL-2 production in response to
      mitogen or alloantigens. However, there was an upward trend (and for p18IIIB a
      statistically significant increase) in the in vitro IL-2 production in response
      to each of five HIV envelope peptides. Potential toxic effects included fatigue,
      arthralgia, edema, myalgia, and headache. Patients also were noted to have weight
      gain averaging 4 kg early in the course of treatment. CONCLUSIONS: These results
      suggest that treatment with rhGH/rhIGF-1 was reasonably well tolerated and that
      modest improvement in HIV-specific immune function was attained. Further studies
      will help clarify the therapeutic potential of rhGH/rhIGF-1 as an
      immunostimulator in the setting of HIV infection.

PMID- 9631144
TI  - Evidence of stable HIV seroprevalences in selected populations in the Democratic
      Republic of the Congo.
AB  - OBJECTIVE: To determine current data on HIV infection and to document changes and
      trends of HIV seroprevalence in selected populations over time in the Democratic
      Republic of the Congo (DRC; former Zaire). METHODS: In February 1997, a large
      serosurvey was conducted on selected population groups from Kinshasa (capital
      city), Mbuji-May (southeast) and Bwamanda (northwest). Samples obtained from
      pregnant women, tuberculosis patients, commercial sex workers, blood donors and
      sexually transmitted disease patients were screened for the presence of HIV
      antibodies by a rapid assay and a commercial enzyme-linked immunosorbent assay.
      All reactive specimens were confirmed and discriminated by a line immunoassay,
      and were further tested for the presence of HIV-1 group O antibodies. Our results
      were compared to data reported in previous studies in Kinshasa. RESULTS: Of a
      total 1970 samples collected, 219 (11.1%) were HIV-1-reactive and seven (0.3%)
      were dually reactive to HIV-1 and HIV-2. No case of HIV-1 group O or HIV-2
      infection was diagnosed. HIV seroprevalence in pregnant women was 3.1% (16 out of
      511), 6.3% (19 out of 300) and 1.5% (one out of 65) in Kinshasa, Mbuji-Mayi, and
      Bwamanda, respectively. HIV seroprevalence in tuberculosis patients was 26% (52
      out of 200), 28% (17 out of 60), and 35.3% (29 out of 83), respectively. HIV
      seroprevalence among blood donors was 3.1% in Kinshasa and 2.8% in Mbuji-Mayi.
      Compared with data from previous studies performed in Kinshasa, no substantial
      change in HIV infection rates was observed among the selected population groups.
      CONCLUSIONS: Our results show that HIV prevalence rates have remained relatively
      unchanged in selected populations despite the political instability and poor
      environment observed since 1991 in DRC. It also shows the presence, still at very
      low rate, of dual HIV-1/HIV-2 seropositivity and a growing problem of HIV
      infection in rural areas. In contrast to other Central African countries, no HIV
      1 group O infections were detected in DRC.

PMID- 9631145
TI  - The incidence and prevalence of HIV infection among childbearing women living in
      Edinburgh city, 1982-1995.
AB  - OBJECTIVE: To track the complete course of the HIV epidemic among women from the
      city of Edinburgh who delivered babies during 1982-1995. METHODS: The performance
      of the modified Serodia HIV test on dried blood spots from archived neonatal
      metabolic screening cards stored for up to 11 years was evaluated by testing 221
      cards from neonates whose mothers' HIV infection status was already known (100
      HIV-positive, 121 HIV-negative). Unlinked anonymous HIV testing of cards from
      neonates born during 1982-1989 was then performed and the resulting prevalence
      data were combined with existing data from 1990-1995. Maximum and minimum limits
      of HIV incidence among women during the 36-month period prior to delivery were
      calculated using data held on a clinical database of HIV-infected pregnant women
      that had been generated under strict conditions of confidentiality; these data
      included the date of the woman's first HIV-positive and, if available, last HIV
      negative specimen. RESULTS: The evaluation revealed a sensitivity of 91%, not
      clearly related to storage time, and a specificity of 100%. HIV infection first
      entered Edinburgh's childbearing population during the early 1980s with
      prevalence peaking at 0.4% in 1986 and then decreasing to 0.1% in 1995; a similar
      incidence profile was seen during this period. Since 1986, the first full year
      that HIV testing was available, 78% of all infections were known during the
      pregnancy, 13% were identified retrospectively, and only 10% (10 cases) remain
      unaccounted for. For infected cases during 1984-1987, 78% were injecting drug
      users (IDU) and only 22% acquired their infection sexually; this distribution had
      reversed by 1992-1995. CONCLUSION: HIV testing of neonatal metabolic screening
      cards stored for up to 11 years can yield results of sufficient accuracy for
      epidemiological purposes. There has been a substantial decline in the prevalence
      and incidence of HIV since the mid-1980s. Although new infections are still
      occurring, the numbers are small. The decline may largely be explained by the
      impact of preventive measures on the spread of HIV amongst IDU, and thus from IDU
      to their sexual partners.

PMID- 9631146
TI  - Effectiveness of psychosocial interventions in preventing HIV risk behaviour in
      injecting drug users.
AB  - OBJECTIVE: To consider evidence for the effectiveness of psychosocial
      interventions in reducing the risk of infection with HIV of injecting drug users.
      METHOD: We reviewed 19 published studies of the effectiveness of individual
      counselling, HIV testing, group interventions, street outreach, and a 'social'
      intervention designed to change norms for safer behaviours. RESULTS: Eight of 15
      studies that examined behavioural outcomes provided evidence of the effectiveness
      of an experimental intervention, compared with a control or comparison group. In
      four of these studies, however, serious design limitations made results difficult
      to interpret. In the other four studies without design limitations, the success
      of the experimental interventions may have been due to their greater length and
      intensity as well as to having been conducted with stable and well-motivated
      populations. Nine of the 15 studies showed evidence of marked behaviorial changes
      in both experimental and comparison group(s), with the changes in many cases
      being sustained for upwards of 12 months. CONCLUSIONS: A close examination of the
      evidence and competing hypotheses for the pattern of results suggests that
      participating in evaluation research may itself be a valuable intervention.
      Implications for the development of interventions include the potential efficacy
      of health risk assessment. Implications for evaluation of interventions include
      the need for developing unobtrusive measures and for assessing the impact of
      behavioural assessments. Despite the large behavioural changes reported in most
      of the studies, a substantial proportion of subjects receiving interventions
      reported unacceptably high levels of risk behaviours. New, more potent
      interventions are needed, such as those designed to change the norms of entire
      communities of drug users concerning safer injection and safer sex.

PMID- 9631147
TI  - HIV surveillance among sexually transmitted disease clinic attenders in
      Amsterdam, 1991-1996.
AB  - OBJECTIVE: To determine trends in HIV prevalence among attenders of a clinic for
      sexually transmitted diseases (STD), with emphasis on heterosexuals who did not
      have a history of injecting drug use. METHODS: Anonymous unlinked HIV surveys
      with individual consent, conducted each half year from 1991 to 1996 (except 1993)
      among STD clinic attenders who came for evaluation of a possible new STD episode.
      RESULTS: Of 10,940 eligible attenders 10,046 (92%) accepted HIV testing. Of all
      tested attenders, 312 (3.1%) were HIV-infected. Overall HIV prevalence decreased
      significantly from 4.6% in 1991 to 2.8% in 1996. HIV prevalence among
      heterosexual men and women who were not injecting drug users was less than 1% in
      all but one survey period. Except for one woman, none of the 48 HIV-infected
      heterosexuals was aware of their current serostatus. Among HIV-infected
      heterosexuals, 21 out of 28 males (75%) and 18 out of 20 females (90%) were of
      non-Dutch origin. HIV prevalence was 16% among all homosexual men, and 12% among
      young homosexual men aged < 30 years. HIV prevalence among young homosexual men
      decreased significantly over time. Among HIV-infected homosexual men, 58% of
      older men and 59% of younger men were not aware of their current HIV infection.
      Rates of current STD were generally significantly higher among HIV-infected
      participants compared with non-HIV-infected participants. CONCLUSIONS: Although
      HIV prevalence among heterosexual clinic attenders is low, there is a clear
      potential for ongoing sexual HIV transmission. Most heterosexually acquired HIV
      infections are found in non-Dutch persons. This observation suggests migration of
      HIV-infected heterosexuals or the separation of Dutch and non-Dutch heterosexual
      networks. Awareness of serostatus is almost non-existent among HIV-infected
      heterosexuals, and is low among male homosexual clinic attenders. To increase
      awareness of current HIV serostatus and possibly decrease risk behaviour, HIV
      counselling and testing should be offered actively to all clinic attenders.

PMID- 9631148
TI  - Cost-effectiveness of antiviral drug therapy to reduce mother-to-child HIV
      transmission in sub-Saharan Africa.
AB  - OBJECTIVE: To assess the potential cost-effectiveness of short-course antiviral
      regimens to prevent mother-to-child transmission (MCT) of HIV in sub-Saharan
      Africa. DESIGN: Cost-effectiveness analysis. METHODS: No intervention was
      compared with three regimens of twice daily zidovudine and lamivudine: regimen A,
      starting at 36 weeks of gestation and continuing to 1 week postpartum; regimen B,
      from intrapartum through 1 week postpartum; and regimen C, intrapartum only.
      Model inputs were estimated from published and unpublished data. Absolute
      percentage reductions in HIV transmission extrapolated from zidovudine
      monotherapy trials were estimated at 12.4, 8.6 and 4.3% for regimens A, B, and C,
      respectively. Outcome measures were net costs to the public sector health-care
      system, cost per infection averted, and cost per disability-adjusted life-year
      (DALY) gained. Multiple sensitivity analyses were conducted. RESULTS: Based on
      the hypothetical efficacy estimates, regimen C was the most cost-effective. For a
      cohort of 100 women with 15% HIV prevalence, net costs to the public sector
      health-care systems were estimated at US$3617 for regimen A, US$ 1667 for regimen
      B, and US$351 for regimen C. Regimen C had a cost of US$ 1129 per HIV infection
      averted and a cost of US$60 per DALY. Regimens B and A cost US$2680 and 5134 per
      infection averted and US$143 and 274 per DALY, respectively. Cost-effectiveness
      declined rapidly at efficacy below 10% or HIV prevalence below 7%. Results were
      very sensitive to antiviral drug costs. For example, at 20% of current prices,
      the cost per DALY for regimen A fell to US$64, and to about US$42 for regimens B
      and C. CONCLUSION: Antiviral therapy may be cost-effective compared with other
      health interventions if HIV prevalence is high, if clinical trials confirm
      estimated efficacies, and if drug prices are reduced.

PMID- 9631149
TI  - Usefulness of HIV-1 V3 serotyping in studying the HIV-1 epidemic in South Africa.

PMID- 9631150
TI  - HIV-1 subtype A in Japan.

PMID- 9631151
TI  - Long-term remission of AIDS-related primary central nervous system lymphoma
      associated with highly active antiretroviral therapy.

PMID- 9631152
TI  - Subtle occurrence of indinavir-induced acute renal insufficiency.

PMID- 9631153
TI  - Highly active antiretroviral therapy in human herpesvirus-8-related body-cavity
      based lymphoma.

PMID- 9631154
TI  - Immune status in HIV-1-infected men and boys with haemophilia in the United
      Kingdom. UK Haemophilia Centre Directors' Organisation.

PMID- 9631156
TI  - Variability in early HIV-1 population dynamics.

PMID- 9631155
TI  - Substance abuse is responsible for most pre-AIDS deaths among women with HIV
      infection in Providence, Rhode Island, USA.

PMID- 9631157
TI  - CD4+ lymphocyte count and plasma HIV RNA levels in a survey of 1602 HIV-infected
      patients in Bordeaux, France, 1996-1997. Groupe d'Epidemiologie Clinique da SIDA
      en Aquitaine.

PMID- 9631158
TI  - Long-term suppression of HIV replication in patients with sustained benefit on
      zidovudine monotherapy.

PMID- 9631159
TI  - Performance-based physician reimbursement and influenza immunization rates in the
      elderly. The Primary-Care Physicians of Monroe County.
AB  - OBJECTIVE: To investigate the effect of performance-based financial incentives on
      the influenza immunization rate in primary care physicians' offices. DESIGN:
      Randomized controlled trial during the 1991 influenza immunization season.
      SETTING: Rochester, New York, and surrounding Monroe County during the Medicare
      Influenza Vaccine Demonstration Project. PARTICIPANTS: A total of 54 solo or
      group practices that had participated in the 1990 Medicare Demonstration Project.
      INTERVENTIONS: All physicians in participating practices agreed to enumerate
      their ambulatory patients aged 65 or older who had been seen during the 1990 or
      1991 calendar years, and to track the immunization rate on a weekly basis using a
      specially designed poster from September 1991 to January 1, 1992. Additionally,
      physicians agreed to be randomized, by practice group, to the control group or to
      the incentive group, which could receive an additional $.80 per shot or $1.60 per
      shot if an immunization rate of 70% or 85%, respectively, was attained.
      MEASUREMENTS: The main outcome measures are the 1991 immunization rate and the
      improvement in immunization rate from the 1990 to 1991 influenza seasons for each
      group practice. RESULTS: For practices in the incentive group, the mean
      immunization rate was 68.6% (SD 16.6%) compared with 62.7% (SD 18.0%) in the
      control group practices (P = .22). The median practice-specific improvement in
      immunization rate was +10.3% in the incentive group compared with +3.5% in the
      control group (P = .03). CONCLUSIONS: Despite high background immunization rates,
      this modest financial incentive was responsible for approximately 7% increase in
      immunization rate among the ambulatory elderly.

PMID- 9631160
TI  - Demographic differences in prostate cancer incidence and stage: an examination of
      population diversity in California.
AB  - INTRODUCTION: Geographic and racial/ethnic variability in prostate cancer
      incidence rates and stage distribution may be partly attributed to differences in
      screening and early detection. METHODS: Using California Cancer Registry data we
      aimed to characterize variability in prostate cancer rates statewide and to
      examine differences in the stage at diagnosis of prostate cancer by racial/ethnic
      group statewide and by census tract per capita income in San Diego County. We
      calculated annual average (1988-1991) age-adjusted incidence rates per 100,000
      (AAIR) of prostate cancer for 49,880 men over age 34 years. Racial/ethnic groups
      were compared using incidence rate ratios (IRR) (AAIR localized plus regional
      stages divided by AAIR distant stage). RESULTS: Statewide, Caucasians showed a
      higher IRR [6.16, 95% confidence interval (CI), 6.00-6.30] than did African
      Americans (2.34, 95% CI, 1.89-2.89), Hispanics (3.84, 95% CI, 3.63-4.05), or
      Asian/others (3.61, 95% CI, 1.80-7.22). Within San Diego County, Caucasians
      living in higher per capita income census tracts (> or = 65th percentile) had a
      significantly higher IRR (8.80, 95% CI 7.84-9.89) than did lower-income tracts
      (5.68, 95% CI, 5.13-6.30). CONCLUSION: Findings from the present and similar
      studies suggest that outcomes research is needed to determine the impact of these
      demographic differences on prostate cancer mortality and quality of life. This is
      particularly important given the current controversy regarding the treatment of
      clinically localized prostate cancers, increasingly found through early
      detection, which often involve difficult choices between aggressive therapies
      including prostatectomy or watchful waiting.

PMID- 9631161
TI  - Impact of receiving blood cholesterol test results on dietary change.
AB  - INTRODUCTION: The study objective was to determine the impact of receiving
      results of a blood cholesterol test on changes in dietary behaviors among
      individuals participating in a Health Risk Appraisal Program. METHODS: This
      randomized trial of maintenance employees at six hospitals included two groups:
      Group 1 received their blood cholesterol test results at the pretest; Group 2
      received results only at the posttest (16-20 weeks later). The pretest interview
      included (1) a 24-hour dietary recall; (2) an evaluation of dietary behaviors and
      suggestions on how to change; (3) height, weight, and blood cholesterol
      measurement. Five hundred employees participated, and 429 eligible employees
      completed both pretest and posttest interviews. RESULTS: Blood cholesterol levels
      decreased by 4.8% (P < .001) and saturated fat intake decreased by 7.4% (P <
      .05). Regression analyses indicated that individuals more likely to have lowered
      saturated fat intake had higher pretest saturated fat intakes, had a family
      history of high blood cholesterol, and were light-maintenance employees (P <
      .05); no other variables were associated (receiving blood cholesterol test
      results, previous blood cholesterol test, pretest blood cholesterol levels,
      personal history of heart disease, BMI, age, gender, tobacco/alcohol use). Among
      subjects with normal cholesterol levels, those not receiving blood test results
      reduced saturated fat intake more than those receiving test results; both groups
      had similar saturated fat intakes (> 12%) greater than recommended intake (<
      10%). CONCLUSIONS: Screening programs should include an assessment of saturated
      fat intake as screening for blood cholesterol may provide normocholesterolemic
      subjects with a false sense of security.

PMID- 9631162
TI  - Validity of self-reported mammography in low-income African-American women.
AB  - BACKGROUND: Mammography screening reduces mortality by 25% to 30% in women aged
      50 to 69. Because mammography screening is often used less frequently than the
      recommended guidelines, many descriptive and intervention studies are underway to
      increase use of this important screening tool. Assessment of intervention effect
      is dependent on valid measurement of mammography use. Although several studies
      have shown a close correspondence between self-report and medical records, most
      had few minority participants. METHODS: The purpose of this report was to compare
      self-reported mammography and medical records of mammography status in a low
      income African-American sample. A total of 229 low-income (at 150% of poverty or
      below) African-American women were interviewed regarding breast cancer screening.
      Response categories that assessed last mammogram were "within the last 12
      months," "13-24 months," and "over 24 months," as well as date and location of
      last mammogram. Self-reported mammography was compared with medical records at
      the facility named by respondents. RESULTS: Comparison with self-report showed
      that only 49% to 60% of reported mammography use could be verified within
      categories. CONCLUSION: Self-report alone may not provide accurate rates of
      mammography compliance. Further research is necessary with ethnic and low-income
      women.

PMID- 9631163
TI  - Enforcement of age-appropriate immunization laws.
AB  - BACKGROUND: The state of North Carolina has statutes that require age-appropriate
      immunization as recommended by the U.S. Public Health Service. Provisions of this
      statute allow for criminal misdemeanor charges and injunctions to be brought
      against parents who do not have their children immunized on time. The decision to
      invoke the age-appropriate immunization statute rests with the health director of
      each county. This study was performed to determine if the county health directors
      were aware of this statute and whether they had ever utilized it to enforce age
      appropriate immunization. METHODS: All health department directors in the state
      of North Carolina (N = 86) received letters inviting them to complete a 20-minute
      structured phone interview at a time of their convenience. Specific questions
      addressed their knowledge of the statutes and the specific penalties available.
      Additional questions addressed their attitudes and beliefs about the law and what
      they believed the state government could do to assist in enforcing the law.
      RESULTS: Interviews were completed for 75 of the 86 (87%) county health
      departments or districts. All respondents reported they were aware, prior to
      receiving the materials informing them of the study, that the state required
      children to be immunized on time. Over 95% reported they knew the law required
      age-appropriate immunization and 100% were aware of school/licensed day-care
      requirements. The vast majority (83%) of county health directors believe that
      criminal misdemeanor charges and injunctions should be brought against parents
      for failing to have their child age-appropriately immunized. However, only 5% (n
      = 4) of health directors reported that their county had ever brought criminal
      misdemeanor charges, and none had filed an injunction against a parent whose
      child was not immunized on time. CONCLUSIONS: Despite the presence of legal
      statutes, there have been only rare efforts to compel age-appropriate
      immunization through enactment and enforcement of criminal penalties on parents.
      Much of the hesitancy for such efforts likely comes from the fear of the
      confusing, hard-to-understand legal procedures and from the potential negative
      impact on public opinion that these tactics may create. Although such actions
      should be taken only as a last resort, they may be necessary on some occasions.

PMID- 9631164
TI  - Weapon-carrying, physical fighting, and fight-related injury among U.S.
      adolescents.
AB  - INTRODUCTION: Access to firearms and other weapons has been cited as an important
      factor contributing to the rise in violence-related injury among adolescents in
      the United States. METHODS: Data from the Youth Risk Behavior Survey supplement
      to the 1992 National Health Interview Survey were analyzed to examine
      relationships among weapon-carrying, physical fighting, and fight-related injury
      among U.S. adolescents aged 12-21 years (N = 10,269). Adjusted odds ratios (OR)
      were used to describe the association of weapon-carrying during the past 30 days
      with physical fighting and fight-related injury during the past 12 months.
      RESULTS: Weapon-carrying (15%) and physical fighting (39%) were common among
      adolescents. One out of 30 (3.3%) adolescents reported receiving medical care for
      fight-related injuries. Controlling for demographic characteristics, youth who
      carried weapons were more likely than those who did not to have been in a
      physical fight (OR = 3.3). The association between weapon-carrying and physical
      fighting was stronger among females (OR = 5.0) than among males (OR = 2.9), but
      did not vary significantly by age, race/ethnicity, or place of residence (urban,
      suburban, rural). Controlling for frequency of physical fighting and
      demographics, adolescents who carried a handgun (OR = 2.6) or other weapon (OR =
      1.6) were more likely than those who did not carry a weapon to have had medical
      care for fight-related injuries. CONCLUSIONS: Among adolescents, weapon-carrying
      is associated with increased involvement in physical fighting and a greater
      likelihood of injury among those who do fight. Efforts to reduce fight-related
      injuries among youth should stress avoidance of weapon-carrying.

PMID- 9631165
TI  - Smoking initiation and cessation in African Americans attending an inner-city
      walk-in clinic.
AB  - OBJECTIVES: Data collected from a population of African Americans were analyzed
      to examine patterns of smoking initiation, smoking cessation, and factors related
      to smoking cessation. METHODS: Over a 4-month period, all (N = 2,928) patients
      attending an inner-city medicine clinic were recruited to participate in a
      smoking intervention trial. Over 99% participated, providing information on their
      smoking experiences, including smoking status (current, former, or never a
      smoker), duration of regular smoking, and year of quitting when applicable. Data
      on African Americans with complete information on these variables (n = 2,428)
      were analyzed with respect to initiation and duration of smoking. RESULTS: More
      than half of African-American smokers in the population studied initiated regular
      smoking after age 19. Later age of initiation of smoking and female gender were
      associated with short duration smoking (i.e., quitting before 10 years of regular
      smoking); these variables, but not age, were identified as significant factors in
      a Cox Proportional Hazards model with duration of smoking as the outcome
      variable. CONCLUSIONS: A sizable opportunity for primary prevention of regular
      smoking appears to exist among African Americans aged 20 to 30 years as evidenced
      by patterns of smoking initiation in the population studied. The importance of
      age at initiation of regular smoking to the duration of smoking is demonstrated
      in this population over a wide range of duration.

PMID- 9631166
TI  - Reducing cigarette sales to minors in an urban setting: issues and opportunities
      for merchant intervention.
AB  - INTRODUCTION: Intervention studies to reduce cigarette sales to minors have been
      conducted primarily in suburban settings. Little is known about sociocultural
      factors influencing cigarette sales to minors in urban settings. This study
      sought to determine sociodemographic and cultural factors that may play a role in
      cigarette sales and in efforts to reduce sales to minors in urban areas. METHODS:
      Merchant education and follow-up surveys were conducted in small local stores in
      predominantly African-American urban census tracts in Baltimore. The stores had
      prior evidence of cigarette sales to minors. RESULTS: Merchants reported
      hostility (66%) and foul language (64%) when they requested youth identification.
      Youthful-oriented advertising of cigarettes was highly prevalent in all stores
      and moreso in stores owned and staffed by Asian merchants. Advertising with
      specific youthful content was predictive (OR = 3.97; 95% CI = 1.70, 9.23; P =
      .0014) of higher requests for cigarettes from minors. CONCLUSIONS: Youth-oriented
      cigarette advertising is a prevalent environmental risk for urban youth.
      Differences between Asian and African-American merchants suggest socioethnic
      factors may be an influential component of illegal sales and educational
      campaigns to reduce smoking among minors.

PMID- 9631167
TI  - Estimating the accuracy of screening mammography: a meta-analysis.
AB  - OBJECTIVE: To estimate the accuracy of mammographic screening. DESIGN: A meta
      analysis of published literature. DATA SOURCES: Published English-language
      randomized controlled trials, case-control studies, and demonstration projects
      involving screening mammography were identified using recent review articles. We
      found additional references using MEDLINE searches combining the MeSH terms
      "mammography," "screening," and/or study authors and locations. STUDY SELECTION:
      We included all studies that provided information to calculate the true-positive
      rate (TPR) and the false-positive rate (FPR) for breast cancer screening. DATA
      EXTRACTION: Reported data were reviewed independently by the authors;
      calculations were compared and discrepancies resolved. We calculated the
      sensitivity as the number of breast cancers detected during the first round of
      screening (true positives) divided by the sum of the true positives and the false
      negatives (defined as cancer discovered within 1 year of screening). False
      positives were determined by biopsy. DATA SYNTHESIS: TPR and FPR values from each
      study were plotted in receiver operating characteristic (ROC) space. Tests of
      homogeneity were performed to assess the validity of using summary ROC curves or
      a single point to summarize the data. The reported TPR and FPR of mammography
      ranged from 83% to 95% and 0.9% to 6.5%, respectively. The sensitivity of
      mammography is higher in women over the age of 50 years. CONCLUSIONS: The
      accuracy of mammography should be recognized and included in discussions about
      policies for screening for breast cancer. This meta-analysis, by quantifying the
      expected TPR/FPR, should assist program planners, physicians, and women to
      understand better the cost and clinical implications of such screening programs.

PMID- 9631168
TI  - American College of Preventive Medicine Practice Policy Statement: adult
      immunizations.

PMID- 9631169
TI  - Production of rat salivary cystatin S variant polypeptides in Escherichia coli.
AB  - Cystatins are protein inhibitors of papain and related cysteine proteinases. A
      series of continuous synthetic peptides corresponding to the entire sequence of
      rat salivary cystatin was used to localize the binding domains of the cystatin to
      papain. Several synthetic peptides, one from the aminoterminal sequence (peptide
      1-24) and others from the carboxylterminal (peptides 66-79, 66-90, 79-90, 79
      114), showed binding to papain, but none of the peptides showed inhibition of
      papain activity. Three recombinant rat salivary cystatin variants (N-terminal
      truncated protein lacking amino acid residues 1-9; variant 49-53, in which amino
      acid residues QVVAG of rat salivary cystatin had been replaced with amino acid
      residues LVL in mutant protein; and variant 65-78, in which amino acid residues
      65-78 had been replaced with amino acids PG in mutant protein) were produced
      using the Escherichia coli expression system pGex-4T. To generate N-terminal
      truncated protein the desired coding region of the cystatin gene was amplified by
      polymerase chain reaction (PCR). To produce the variants 49-53 and 65-78, a PCR
      based approach of gene splicing by overlap extension was used. Recombinant
      cystatin proteins were produced as insoluble inclusion bodies as fusion proteins
      with a glutathione S-transferase (GST) carrier. After solubilization with urea
      the GST carrier was cleaved from the fusion protein with thrombin and cystatin
      variants purified by fast liquid chromatography on a MonoQ column. The purified
      proteins reacted with antibodies to rat salivary cystatin. The N-terminal
      truncated and variant 49-53 exhibited very little inhibitory activity towards
      papain, whereas variant 65-78 exhibited papain-inhibitory activity similar to the
      full-length recombinant cystatin.

PMID- 9631170
TI  - Coexpression of vasoactive intestinal polypeptide and substance P in
      reinnervating pulpal nerves and in trigeminal ganglion neurones after axotomy of
      the inferior alveolar nerve in the rat.
AB  - The effect of this axotomy on the expression of vasoactive intestinal polypeptide
      (VIP) in trigeminal ganglion neurones and nerve fibres in the first molar was
      examined immunohistochemically 3 weeks postsurgically in rats. A distinct
      upregulation of VIP-like immunoreactivity was found in 3 to 4% of the neurones
      (mean dia., 20.9 +/- 0.45 microns; mean cross-sectional area, 367 +/- 13.2
      microns 2) in the mandibular region after axotomy. An almost complete
      coexpression was registered in neurones upregulated for VIP and growth-associated
      protein 43. Coexpression of VIP and substance P (SP) was found in a small number
      of the immunoreactive (IR) small-sized neurones, mainly in those in which VIP and
      SP were both weakly immunoreactive. In the uninjured ganglion, weakly labelled
      VIP-positive granules were frequently traced at high magnification in the
      cytoplasm of small neurones. No VIP-IR fibres were found in the control molar
      pulp, except for a few in the root pulp near the apex. However, 3 weeks after
      axotomy, a number of VIP-containing nerve fibres were found in the molar pulp and
      apical periodontium. Coarse VIP-IR fibres directed towards the odontoblast layer
      were a common finding. In some of these fibres VIP was shown to colocalize with
      SP. These results indicate that VIP is clearly expressed and transported in
      regenerating primary afferent neurones after axotomy of the inferior alveolar
      nerve.

PMID- 9631171
TI  - Differential responses of mandibular condyle and femur to oestrogen deficiency in
      young rats.
AB  - This response of condyle and femur was evaluated by histomorphometry. Five female
      Sprague-Dawley rats, 6 weeks of age, were subjected to bilateral ovariectomy, and
      five others were sham-operated. They were then killed 32 days later. Ovariectomy
      significantly increased the total thickness of the condylar cartilage and distal
      femoral growth-plate cartilage in the young, growing rats. Ovariectomy caused a 2
      fold increase in thickness of the proliferative layer and a 4-fold increase in
      thickness of the hypertrophic layer in the condylar cartilage, and a 1.3-fold
      increase in thickness of the proliferative layer in the epiphyseal growth
      cartilage of the femur. Ovariectomy had no effect on the percentage of trabecular
      bone volume, the percentage of the bone surface covered by osteoblasts (Ob.S/BS)
      and osteoclasts (Oc.S/BS), and number of osteoclasts per bone surface (N.Oc/BS)
      in the mandibular condyle. On the contrary, ovariectomy caused a 68.5% decrease
      in bone volume, a 4-fold increase in Ob.S/BS, and 2-fold increases in Oc.S/BS and
      N.Oc/BS in the secondary spongiosa of the rat distal femur. Thus there was a
      prominent difference in the response to oestrogen deficiency between the
      mandibular condyle and femur in young growing rats.

PMID- 9631172
TI  - Evidence for presynaptic cholinergic receptors in sympathetic nerves in human
      dental pulp.
AB  - The purpose of this study was to determine whether presynaptic cholinergic
      receptors are present in sympathetic nerves in human dental pulp. Pulp was
      incubated with [3H]noradrenaline (0.6 mumol/l) for 30 min and then superfused
      with Krebs' solution at 1.0 ml/min. Electrical stimulation (100 sec, 5 Hz)
      increased the overflow of [3H]noradrenaline into the superfusate. Carbachol (10
      and 100 mumol/l), an agonist of muscarinic receptors, decreased the stimulation
      induced (SI) overflow of 3H, an effect blocked by atropine but not hexamethonium.
      Carbachol, atropine and hexamethonium had no effect on the resting overflow.
      Nicotine (10 mumol/l) increased the resting overflow and inhibited the SI
      overflow, although the inhibition was variable. Cytisine, another agonist of
      nicotinic receptors, also increased the resting overflow, but did not affect the
      SI overflow. To ascertain whether the actions of nicotine and electrical
      stimulation were influenced by the release of nitric oxide (NO), the effects of
      an NO donor and two NO-synthase inhibitors were examined. With the exception of
      one of the NO-synthase inhibitors (L-NAME), the agents were without effect on the
      overflow of 3H in the absence or presence of nicotine. It was concluded that
      sympathetic nerves in human dental pulp possess (a) presynaptic muscarinic
      receptors that inhibit the SI release of noradrenaline, and (b) nicotinic
      receptors that evoke the release of noradrenaline and that inhibit the SI release
      of the transmitter. The results do not point to a significant role for NO in the
      effects of stimulation or nicotine on the overflow of 3H.

PMID- 9631173
TI  - Sibling similarities in the tempo of human tooth mineralization.
AB  - The extent of tooth mineralization is a useful estimate of a child's
      physiological age it reflects the rate at which the child is developing towards
      maturity. As it is not known to what degree dental age is regulated by the
      genotype, this investigation estimated familial resemblance in the tempo of tooth
      mineralization. Panoramic radiographs of the children in 185 sibships were scored
      for stages of tooth formation, and dental age was calculated from sex-specific
      standards. Intraclass correlations of mineralization tempo were computed for
      maxillary and mandibular canines, premolars, second molars, and third molars.
      Correlations of mineralization tempo were significantly different than zero for
      all 10 teeth and ranged from 0.17 (SE = 0.06) for the mandibular second molar to
      0.43 (SE = 0.05) for the mandibular second premolar. Intraclass correlations
      increased significantly when multiple teeth were used to more comprehensively
      define each child's dental age. Using an unweighted average of all 10 tooth types
      yielded a correlation of 0.41 (SE = 0.05). It appears, then, that a considerable
      proportion of the total variability in tooth-mineralization rate can be
      attributed to transmissible effects operating in the population under
      investigation.

PMID- 9631174
TI  - Activation of phospholipase D by ADP-ribosylation factor in rat submandibular
      acinar cells.
AB  - The hydrolysis of membrane phosphatidylcholine by the enzyme phospholipase D is a
      key initial step in the intracellular release of the signalling molecules
      phosphatidic acid, diacylglycerol and arachidonic acid. Guanine nucleotide
      dependent pathway leading to PLD activation were investigated in enzymatically
      dispersed rat submandibular acinar cells. Guanosine 5'-O-[gamma-thio]triphosphate
      (GTP gamma S) caused the time- and concentration-dependent stimulation of PLD in
      permeabilized cells. This effect was lost in prepermeabilized cells, from which
      cytosolic components had been allowed to leak, but was restored when endogenous
      cytosol, or cytosol from platelets, was added back to such cells. PLD was also
      activated in cytosol-depleted cells by GTP gamma S in combination with purified
      ARF (ADP-ribosylation factor), a low M(r) guanine nucleotide-binding protein of
      the ras superfamily. Additional evidence for the involvement of ARF in PLD
      activation was the inhibition of carbachol- or GTP gamma S-induced stimulation of
      the enzyme by brefeldin A, a blocker of ARF activation; and the observed
      translocation of ARF from cytosol to membrane on GTP gamma S treatment in
      permeabilized cells. The heterotrimeric G-protein stimulator, AlFn, also
      activated PLD, and this response, too, was inhibited by brefeldin A, suggesting
      the downstream involvement of ARF in coupling AlFn action to phospholipase D
      elevation. PLD activation caused by both GTP gamma S and AlFn was only partially
      reduced after treatment of cells with U73122, a demonstrated inhibitor of
      phospholipase C in the Gq-coupled phosphoinositide signal-transduction pathway.
      It is therefore proposed that in rat submandibular mucous acinar cells, a guanine
      nucleotide-regulated PLD activation pathway exists that involves the sequential
      actions of a G heterotrimeric protein and ARF. It is further suggested that this
      pathway is independent of the Gq/PLC/phosphatidylinositol signal transduction
      system.

PMID- 9631175
TI  - The regulating manner of opioid receptors on distinct types of calcium channels
      in hamster submandibular ganglion cells.
AB  - It is well known that opioids produce inhibitory effects on neuronal activity and
      on synaptic transmission at most synapses. In this study, we have investigated
      the effects of opioids on the low voltage- and high voltage-activated calcium
      channels in acutely dissociated submandibular ganglion (SMG) neurons, using the
      whole-cell configuration of the patch-clamp technique. The kappa-opioid-receptor
      agonist U-50488H, the delta-opioid-receptor agonist [D-Pen 2,5]-enkephalin and
      the mu-opioid-receptor agonist [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin inhibited
      L-, N- and P/Q-type calcium-current components in a dose-dependent manner at 10
      nM-1 microM, respectively, but not the T-type calcium current. These inhibitory
      effects were antagonized by naloxone (1 microM). The results showed that three
      types of opioid receptors regulate the L-, N- and P/Q-types of calcium channels,
      respectively, but not the T-type, in SMG neurones.

PMID- 9631176
TI  - Immunolocalization of glycosaminoglycans in ageing, healthy and periodontally
      diseased human cementum.
AB  - The distribution of glycosaminoglycans in the extracellular matrix of human
      cementum was investigated in periodontally involved and periodontal disease-free
      teeth separated into eight different age groups (from 12 to 90 years), to
      investigate possible changes in the distribution of glycosaminoglycan species
      associated with ageing and periodontal disease. A standard indirect
      immunoperoxidase technique was used, with a panel of monoclonal antibodies, 2B6,
      3B3, 5D4, and 7D4, that recognize epitopes in chondroitin-4-sulphate/dermatan
      sulphate (C-4S/DS), chondroitin-6-sulphate (C-6S), keratan sulphate (KS) and a
      novel sulphated chondroitin sulphate (CS) epitope, respectively. Intense positive
      staining for C4-S/DS was observed at the margins and lumina of almost all the
      lacunae and canaliculi in cellular cementum in all sections. Immunoreactivity to
      C6-S, KS and novel CS epitopes was limited to a proportion of lacunae and
      canaliculi in all sections, although C6-S and the novel CS epitopes were more
      widely distributed than KS. In acellular cementum, there was no demonstrable
      staining for any of the glycosaminoglycans except where periodontal ligament
      (Sharpey's) fibres insert; periodontal ligament fibres inserting in cellular
      cementum also demonstrated positive immunoreactivity. In addition, the
      cementoblasts on the outer root surface, as well as the pericellular areas around
      a proportion of these cells, demonstrated positive immunoreactivity. These
      results indicate that glycosaminoglycan species present in human cementum include
      C4-S, DS, C6-S, and novel sulphated CS epitopes. KS is also present in cementum
      but is limited to a more restricted proportion of lacunae and canaliculi.
      Regional differences in the distribution of glycosaminoglycans exist between the
      two cementum types, but no qualitative differences in that distribution were
      observed between the various age groups or between periodontally involved and
      periodontal disease-free teeth. The immunoreactivity observed in a proportion of
      lacunae after staining for C6-S, KS, and novel sulphated CS epitopes could
      suggest the existence of different cementocyte subpopulations.

PMID- 9631177
TI  - Differentiation of oral Actinomyces species by 16S ribosomal DNA polymerase chain
      reaction-restriction fragment length polymorphism.
AB  - 16S rDNA polymerase chain reaction-restriction fragment length polymorphism (PCR
      RFLP) was used to generate restriction profiles of the reference strains,
      including the American Type Culture Collection type strains, of oral Actinomyces
      spp., i.e., A. israelii, A. gerencseriae, A. naeslundii genospecies 1 and 2, A.
      odontolyticus, A. meyeri and A. georgiae, and 23 Actinomyces strains isolated
      from human dental plaque. The 16S rRNA gene sequences from isolated genomic DNA
      samples were amplified by PCR. The PCR products were purified and characterized
      by single digestion with four restriction endonucleases, i.e., MnlI, HaeIII,
      CfoI, or HpaII. Among them, MnlI was found to discriminate the respective
      reference strains. The clinical isolates were assigned to one of the species,
      i.e., A. gerencseriae, A. naeslundii genospecies 1 and 2 and A. odontolyticus, on
      the basis of their restriction profiles by single digestion with MnlI. Thus, 16S
      rDNA PCR-RFLP, using MnlI, is a rapid and reliable method for the differentiation
      of oral Actinomyces spp.

PMID- 9631178
TI  - Mounting technique allows observation of immuno-labeled cells on plastic
      coverslips.

PMID- 9631179
TI  - Double labeling for whole-mount in situ hybridization in mouse.

PMID- 9631180
TI  - X-gal staining of Drosophila embryos compatible with antibody staining or in situ
      hybridization.

PMID- 9631181
TI  - pMECA: a cloning plasmid with 44 unique restriction sites that allows selection
      of recombinants based on colony size.

PMID- 9631182
TI  - Protection of proteolysis-prone recombinant proteins in baculovirus expression
      systems.

PMID- 9631183
TI  - Successful expression of a selenomethionyl protein under control of the
      temperature-sensitive lambda repressor requires higher than normal temperature.

PMID- 9631184
TI  - Genomic DNA extraction from small amounts of sera to be used for genotype
      analysis.

PMID- 9631185
TI  - Disposable device for the isolation of DNA from agarose gels.

PMID- 9631186
TI  - Quantification of low-copy transcripts by continuous SYBR Green I monitoring
      during amplification.
AB  - Continuous fluorescence observation of amplifying DNA allows rapid and accurate
      quantification of initial transcript copy number. A simple and generic method for
      monitoring product synthesis with the double-stranded DNA dye, SYBR Green I
      provides initial template copy number estimation limited only by stochastic
      effects. To reach this degree of sensitivity, two methods were used. First,
      specific products generally have a higher melting temperature than nonspecific
      products, and therefore, specific product formation was monitored by fluorescence
      acquisition at temperatures at which only specific products are double-stranded.
      Second, anti-Taq antibodies were used to reduce nonspecific product generation.
      The log-linear portion of the fluorescence vs. cycle plot was extended to
      determine a fractional cycle number at which a threshold fluorescence was
      obtained. These fractional cycle numbers were plotted against the log of starting
      template copies to give linear standard curves from purified PCR products,
      allowing easy estimation of cDNA unknowns over a 10(6)-fold range. A single
      template molecule per reaction could be distinguished from the absence of
      template, although stochastic effects increased the variance of concentration
      estimates below 10 copies. Above 10 copies per reaction, typical replicate
      coefficients of variation were 6%-37%, with better precision at higher copy
      numbers.

PMID- 9631187
TI  - Improving sensitivity of the electrophoretic mobility shift assay by restricting
      tissue phosphatase activities.
AB  - Elucidating DNA-protein interactions at the molecular level is a prerequisite in
      understanding the way a transcriptionally active gene is regulated in various
      tissues. A number of techniques are presently available for this particular type
      of analyses, of which, the electrophoretic mobility shift assay (EMSA) is
      certainly the preferred one and likely the most sensitive and powerful. EMSA is
      widely used in combination with nuclear extracts obtained from cultured cells.
      However, its use with crude extracts prepared from whole animal tissues is still
      restricted. The restriction is partly due to numerous enzymatic activities, such
      as proteases and deacetylases, that strongly interfere with the EMSA's
      sensitivity. In addition to endogenous proteases, which can be inhibited by the
      addition of protease inhibitors to the buffers used, crude nuclear extracts
      obtained from whole animal tissues are often contaminated with considerable
      amounts of highly active endogenous phosphatases. Some of these enzymes
      substantially interfere with the ability of the EMSA to unravel specific DNA
      protein interactions by removing the 5'-[32P] end-labeled phosphate of the DNA
      probe used for the binding assay. In this study, we evaluated whether we can
      restore the sensitivity of the EMSA by modifying the conditions under which the
      DNA-protein binding reaction is normally performed. Dephosphorylation by
      endogenous tissue phosphatases of the labeled probe used in our assays was
      drastically prevented by simply reducing both the temperature at which the
      binding reaction was normally performed and the time allowed for the DNA-protein
      interaction to occur.

PMID- 9631188
TI  - Selection strategy for site-directed mutagenesis based on altered beta-lactamase
      specificity.
AB  - Conventional approaches to oligonucleotide-directed mutagenesis rely upon the
      application of a selection strategy to maximize mutagenesis efficiencies. We have
      developed a mutagenesis procedure that incorporates a novel antibiotic resistance
      for selection. The selection involves altering the substrate specificity of TEM-1
      beta-lactamase, the enzyme responsible for bacterial resistance to beta-lactam
      antibiotics such as ampicillin. The gene encoding beta-lactamase is commonly
      found on cloning and shuttle vectors used in molecular biology. Amino acid
      substitutions in several active site residues of beta-lactamase result in
      increased hydrolytic activity against extended-spectrum penicillins and
      cephalosporins. This increased activity confers a novel resistance specific to
      the mutant and thus provides the basis of the selection strategy. We describe a
      simple and efficient mutagenesis procedure and its application to creating a
      range of oligonucleotide-directed mutants.

PMID- 9631189
TI  - Molecular analysis of animal and plant cells is facilitated by their attachment
      to collodion (cellulose nitrate) films.
AB  - A procedure for the efficient transfer of cell monolayers, cultured on glass
      coverslips, to microscopy slides has been developed. This technique involves the
      coating of the upper surface of an ethanol-fixed cultured cell layer with a film
      of collodion dissolved in n-amyl acetate. The dry collodion-coated cell layer can
      then be detached by rehydrating it for 1 h under water or phosphate-buffered
      saline and then carefully peeling it away from the coverslip using a pair of
      tweezers. Once a cell layer has been so mounted, it can be subjected to rough
      treatment such as proteolytic degradation (which greatly improves the signal-to
      noise ratio in procedures like in situ hybridization [ISH] or primed in situ
      synthesis [PRINS]) without running the risk of cell detachment because of the
      partial or total degradation of the extracellular matrix. As an example of its
      application, we show a PRINS of telomeres from mouse fibroblasts. The high
      mechanical strength of collodion ensures that the structural integrity and
      morphology of the cell layer is maintained under experimental conditions where
      the collodion itself is insoluble. In addition to its use on cell layers,
      collodion can be used for the production of support films for (i) attaching
      suspension cell cultures, (ii) immobilizing cells normally cultured in suspension
      (such as tobacco BY2 cells or germinating tobacco pollen grains) or (iii)
      planting cryostat sections to microscopy slides. The value of this technique lies
      in its ease of use and the large number of different applications, in both the
      plant and animal fields of research, to which it may be applied.

PMID- 9631190
TI  - dsDNA stability dependence on pH and salt concentration.

PMID- 9631191
TI  - Identification and analysis of weak linear banding patterns of fish chromosomes
      with a computer-based densitometric method.

PMID- 9631192
TI  - Emulation of an ELISA reader and quantitative image analysis using the computer
      program Digital-OD.
AB  - Here, we present a Microsoft Windows application that has been written to emulate
      a microplate reader. After scanning a standard 96-well microplate, color
      gradations in the slots can be analyzed quantitatively and be used for the
      estimation of enzyme kinetics, binding assays or concentration determination. In
      a test, series accuracy of the program was determined. We show that the returned
      optical densities correlated highly with the true concentrations (r > 0.97).
      Thus, the software is useful for a wide number of applications. Further, the
      program is easy to handle and is available free of charge.

PMID- 9631193
TI  - Correcting data shifts in gel files created by Model 377 DNA Sequencers.

PMID- 9631194
TI  - Reconstructing fragmented gel files created by Model 377 DNA Sequencers.

PMID- 9631195
TI  - Stereo-4-D reconstruction and animation from living fluorescent specimens.
AB  - We present a novel approach to the viewing and analysis of 4-dimensional (4-D)
      data sets recorded from live fluorescent samples. With stereo-4-D
      reconstructions, the observer manipulates a rotatable projection of the full 3
      dimensional (3-D) specimen while simultaneously controlling animation of the
      recording forward or backward in time. The result is a unique lifelike
      perspective on the development of an entire living subject. Here, we apply this
      technique to the observation of the cell membranes of developing Caenorhabditis
      elegans. Embryos labeled with the vital plasma membrane probe FM 4-64 were imaged
      by multiphoton laser scanning fluorescence microscopy, yielding 4-D data sets of
      entire embryos over several hours of development. Stereo 4-D and standard focal
      plane 4-D viewing of these novel time-lapse recordings provide the observer with
      detail at both the subcellular and whole-animal level from a single data set and
      produce a unique record of the lineage, cell shape changes, cell contacts and
      morphogenetic dynamics that make up embryogenesis. The procedures by which stereo
      4-D reconstructions are created and viewed rely on public domain software running
      on a personal computer and should therefore be accessible by a general audience.
      Data output utilizes the versatile and well-supported QuickTime animation format.
      Additional features allow for stereo-4-D reconstruction of isolated 3-D volumes
      of interest from within the larger specimen.

PMID- 9631196
TI  - Improving read lengths by recomputing the matrices of Model 377 DNA Sequencers.

PMID- 9631197
TI  - Identification and verification of differential display cDNAs using gene-specific
      primers and hybridization arrays.
AB  - An accurate and streamlined approach to differential display (DD) band
      identification and verification is described. To minimize false positives, the
      strategy avoids the use of impure Northern blot probes obtained from PCR
      amplified DD bands. To increase throughput, the cloning of DD bands is replaced
      by a gene-specific primer approach, and hybridization arrays are used in place of
      Northern blots. In summary, DD bands obtained with long primers were directly
      sequenced to allow the design and synthesis of gene-specific primers, which were
      then used to PCR-amplify homogeneous probes for the verification of expression
      patterns by hybridization array analysis. Differential expression of 60 of the 63
      genes tested was confirmed. Thus, false positives are not inherent to DD. The
      results demonstrate the power of DD used with hybridization arrays to rapidly
      generate information on expression patterns of differentially expressed genes.

PMID- 9631198
TI  - Mutational analysis using enriched PCR and cycle sequencing.

PMID- 9631199
TI  - Green fluorescent protein tag for studies of drug-induced translocation of
      nucleolar protein RH-II/Gu.
AB  - We have constructed a human osteogenic sarcoma cell line, U-2 OS/GFP-Gu, that
      expresses nucleolar RNA helicase RH-II/Gu tagged with green fluorescent protein
      (GFP). The presence of a GFP tag does not inhibit RNA helicase, RNA folding and
      ATPase activities of RH-II/Gu protein. The derived cell line responds to
      cytotoxic agents like the parental cell line U-2 OS. In the presence of either
      actinomycin D or toyocamycin, the GFP-RH-II/Gu fusion protein translocates from
      the nucleolus to the nucleoplasm in the same way as the translocation of
      endogenous RH-II/Gu. The drug-induced translocation of GFP-RH-II/Gu is easily
      monitored by direct observation of live cells in vivo. This cell line can be used
      to screen cytotoxic drugs and to study the mechanisms of drug-induced
      translocation of RH-II/Gu. The cellular localization of RH-II/Gu during the cell
      cycle-dependent formation of the nucleolus is readily monitored. Real-time
      results are obtained more quickly without the disadvantages associated with cell
      fixation and immunofluorescence-based staining.

PMID- 9631200
TI  - Identification of anti-invasive but noncytotoxic chemotherapeutic agents using
      the tetrazolium dye MTT to quantitate viable cells in Matrigel.
AB  - Screening methods for chemotherapeutic agents usually rely on the cytotoxic
      properties of the drugs. However, agents that inhibit invasion may have more
      efficacy and cause fewer side effects. Various cellular invasion assays have been
      used to evaluate these types of compounds, including the modified Boyden chamber,
      monolayer wound models and Matrigel outgrowth assays. In this report, we have
      combined the use of the Matrigel outgrowth assay with the 3-(4,5-dimethylthiazol
      2-yl)-2,5-diphenyl tetrazolium bromide (MTT) visualization and cell viability dye
      to visualize invasive cells on Matrigel without magnification. Extraction of the
      dye's formazan byproduct allows cell viability to be assessed. Using several
      invasive and noninvasive cell lines, the utility of the method for various target
      cells was verified. Several established chemotherapeutic agents were also
      screened for their anti-invasive and/or cytotoxic effects when cultured on
      Matrigel. Our results suggest that this method may be an easy, inexpensive and
      nonradioactive alternative for both enumerating cells on Matrigel and screening
      various tumor cell lines treated with chemotherapeutic agent to look for
      compounds with noncytotoxic but anti-invasive properties.

PMID- 9631201
TI  - Sequence analysis of mitochondrial DNA hypervariable regions using infrared
      fluorescence detection.
AB  - The non-coding region of the mitochondrial genome provides an attractive target
      for human forensic identification studies. Two hypervariable (HV) regions, each
      approximately 250-350 bp in length, contain the majority of mitochondrial DNA
      (mtDNA) sequence variability among different individuals. Various approaches to
      determine mtDNA sequence were evaluated utilizing highly sensitive infrared (IR)
      fluorescence detection. HV regions were amplified either together or separately
      and cycle-sequenced using a Thermo Sequenase protocol. An M13 universal primer
      sequence tail covalently attached to the 5' terminus of an amplification primer
      facilitated electrophoretic analysis and direct sequencing of the amplification
      products using IR detection.

PMID- 9631202
TI  - Drawing conclusions: a re-examination of empirical and conceptual bases for
      psychological evaluation of children from their drawings.
AB  - PURPOSE: Although consideration of children's art work (usually drawings) in
      clinical investigations of children referred to psychologists is fairly common,
      there is little evidence for the reliability and validity of such assessments. We
      consider a variety of possible mechanisms which could operate to influence the
      characteristics of children's drawings, and review the evidence that such
      mechanisms operate to allow meaningful psychological evaluations of children from
      their drawings. METHODS: The problem for making a reliable interpretation of the
      significance of a drawing is that a given feature could plausibly support several
      very different interpretations, depending which of many possible processes was
      active or dominant in the production of the drawing. Evidence from studies of
      clinical populations and experimental studies with non-selected samples are
      reviewed in the light of these possibilities. RESULTS: The review indicates that
      drawings are inaccurate and unreliable as personality or state assessments but
      can be influenced by children's emotional attitudes towards the topics depicted.
      The form of that expression, however, may be personal and idiosyncratic. Analogue
      studies of these effects undertaken with non-clinical samples under controlled
      conditions have produced mixed results. At best the reported effects are small.
      CONCLUSIONS: Children's drawings on their own are too complexly determined and
      inherently ambiguous to be reliable sole indicators of the emotional experiences
      of the children who drew them. Further research is needed to establish the extent
      to which such drawings can usefully facilitate assessment of children by other
      means or provide useful support as one of several converging lines of evidence.

PMID- 9631203
TI  - The effects of imagery and sensory detection distractors on different measures of
      pain: how does distraction work?
AB  - OBJECTIVES: Two experiments compared the effects of different distraction tasks
      on pain. Based on multiple-resource theory, Expt 1 predicted that the more a
      distractor shares processing resources with pain perception the greater the
      interference between the two. Experiment 2 tested whether the emotional content
      of the distractor would differentially effect measures that are supposedly
      reflective of the affective component of pain. DESIGN: Both experiments used
      repeated measures designs, with counterbalanced distraction conditions. METHODS:
      In Expt 1 20 participants indicated their pain threshold. No instructions, or one
      of three distraction conditions were presented across four blocks of potassium
      iontophoresis. The distractors were: thermal and light detection, and neutral
      imagining. In Expt 2 30 participants had three blocks of pain threshold, pain
      tolerance, and pain rating trials. For threshold, tolerance, and rating trials,
      one block was without distraction, a second block was completed during light
      detection, and a third block while imagining an enjoyable holiday. RESULTS: In
      Expt 1 all the distractors increased pain threshold. The two detection tasks were
      similarly effective, and more so than the imagination task. Performance on the
      two detection tasks was impaired by painful stimulation similarly for both tasks.
      In Expt 2 the visual detection distractor increased pain threshold and tolerance
      and reduced pain ratings while pleasant imagery only increased pain threshold.
      CONCLUSIONS: These results indicate that a task that requires attention to
      external cues has more impact on pain than either a positive or neutral
      imagination task. However, it is not clear that the specific resources used by
      the distraction tasks moderated pain differentially as predicted by multiple
      resource theory.

PMID- 9631204
TI  - Alliance structure assessed by the Agnew Relationship Measure (ARM).
AB  - OBJECTIVES: We used a new instrument, the Agnew Relationship Measure (ARM), to
      examine the alliance's dimensionality and to construct scales for use in future
      studies. DESIGN: We studied the alliance as reported on the ARM by both clients
      and therapists in the Second Sheffield Psychotherapy Project, a randomized
      comparison of two contrasting time-limited psychotherapies for depression.
      METHODS: Clients (N = 95) and therapists (N = 5) completed parallel forms of the
      (ARM) after every session (N = 1120). RESULTS: Five scales were constructed,
      based on results of simultaneous components analyses and considerations of
      conceptual coherence and comparability across client and therapist perspectives.
      CONCLUSIONS: Bond, partnership, and confidence overlapped statistically
      (consistent with previous studies), but there are conceptual and empirical
      reasons for retaining the distinctions. Openness represented a relatively
      independent dimension. The client initiative scale had low internal consistency
      but the items may have value for future investigations.

PMID- 9631205
TI  - Cognitive assessment of voices: further developments in understanding the
      emotional impact of voices.
AB  - OBJECTIVES: This study examines cognitive behavioural assessment of auditory
      hallucinations ('voices') in people with psychoses. It aims to compare findings
      with previous work and validate the Assessment of Voices Schedule (Chadwick &
      Birchwood, 1994). Data were collected on appraisals of voices in relation to the
      self. It was hypothesized that self-appraisals may be a further factor in
      understanding the emotional impact of voices. DESIGN: A replication study where
      data were collected from a new sample of participants and compared with a
      previous independent sample. METHOD: Voices of 30 patients with a diagnosis of
      schizophrenia were assessed using a semi-structured interview and questionnaires.
      Thought-chaining was used to assess appraisals of the voice in relation to the
      self. RESULTS: Compared to the previous study, current participants were
      significantly less likely to believe in the omnipotence of their voices, to view
      their voices as omniscient and to have a positive affective response to
      benevolent voices. Similar numbers in this study construed their voices as
      malevolent, but fewer participants in this sample had benevolent voices. There
      were no significant differences between samples in behavioural responses to
      voices or in the affective responses to malevolent voices. The Assessment of
      Voices Schedule was found to have generally good test-retest and inter-rater
      reliability. Extremely negative self-appraisals were common, as were negative
      affective responses to the voice experience and low self-esteem. CONCLUSION: The
      implications of these findings for both cognitive behavioural models and therapy
      are discussed.

PMID- 9631206
TI  - Customary physical activity and gender as precursors for late life personal
      disturbance.
AB  - OBJECTIVES: To examine whether customary physical activity (CPA) and gender are
      precursors for personal disturbance in later life. DESIGN: The study was part of
      a longitudinal study, with data collected in 1985 and 1989. Measures of CPA were
      obtained in men and women who by 1989 had developed elevated levels of personal
      disturbance. A case-control design was used: the cases were matched with controls
      on their 1985 levels of personal disturbances, gender and age. METHODS: Levels of
      personal disturbance were measured using the Symptoms of Anxiety and Depression
      (SAD) Scale. CPAs were assessed using five continuous and two discrete measures
      of physical activity, including indoor productive activity, outdoor productive
      activity and flexibility. The cases were 26 women and 11 men and the controls
      were 26 women and 11 men. RESULTS: Both CPA and gender were found to be
      precursors for later elevated personal disturbance. Specifically, indoor and
      outdoor productive activity and activities requiring flexibility were precursors
      for elevated personal disturbance. The effects of gender were even more specific:
      a main effect for gender was found for indoor productive activity (women doing
      more than men); and an interaction effect was observed between personal
      disturbance and gender for outdoor productive activity (the difference between
      depressed and non-depressed men is greater than between depressed and non
      depressed women). CONCLUSIONS: The study found that both CPA and gender were
      precursors for elevated levels of personal disturbance. However, the effects of
      both CPA and gender were quite specific.

PMID- 9631207
TI  - An examination of the effects of gentle teaching on people with complex learning
      disabilities and challenging behaviour.
AB  - OBJECTIVES: This study was conducted to investigate the efficacy of gentle
      teaching when compared with individual educational programming (IEP) for a group
      of people with complex learning disabilities and challenging behaviour. DESIGN:
      An A-B design was used, in which gentle teaching was introduced as an addition to
      the IEP procedures already in place. Other designs, such as reversal, multiple
      baseline or group comparisons would have been impractical in this clinical
      setting. METHODS: Thirteen students and seven staff were observed, using a hand
      held computer for direct observations, and video-recordings for measures of
      interaction. Staff attitudes to gentle teaching and to the IEP system were also
      assessed. The intervention was systematic workshop-based training in gentle
      teaching for all staff. Measures were taken pre-intervention for 13 weeks and
      post-intervention for 23 weeks. Approximately 45 hours of direct observational
      data and over 50 hours of video-recording were analysed. RESULTS: We found very
      few effects of gentle teaching. Wherever there were differences between gentle
      teaching and IEP these were in favour of gentle teaching, although they were
      generally relatively minor in terms of clinical (rather than statistical)
      significance. Inter-rater reliabilities were generally poor, although the figures
      for those categories where there was a difference between gentle teaching and IEP
      were amongst the most respectable. CONCLUSIONS: Gentle teaching did not have a
      major impact on staff behaviour, and no discernible effect on student behaviour,
      but it did not lead to poorer interactions and may be a useful adjunct to more
      structured approaches such as individual educational programming.

PMID- 9631208
TI  - The 'Severe Impairment Battery': assessing cognitive ability in adults with Down
      syndrome.
AB  - OBJECTIVES: To examine the utility of the 'Severe Impairment Battery' (SIB-
      Thames Valley Test Company) in assessing cognitive ability of adults with Down
      syndrome. DESIGN: A within-subject repeated measures design was used to determine
      test-retest reliability of the SIB and the Vineland Adaptive Behaviour Scales
      (Interview Edition--Survey Form, 1984) were used to establish SIB criterion
      validity. METHODS: Thirty-three adults with Down syndrome (from 152 known to an
      NHS Trust learning disability service) were selected on the basis of their or
      their carers' written consent. At the first administration of the SIB with the
      participant, a staff member completed a Vineland ABS. Thirty days later, the SIB
      was readministered to the participant. RESULTS: Test-retest reliability of the
      SIB was high as was criterion validity determined by correlating SIB and Vineland
      ABS scores. Floor effects were not encountered. CONCLUSIONS: The SIB can
      successfully be used with adults with Down syndrome to assess cognitive
      functioning over a wide range of ability and may be useful, if used
      longitudinally, in assessing for deterioration in cognitive functioning
      associated with dementia. Methodological limitations are discussed.

PMID- 9631210
TI  - Development of the Cambridge Contextual Reading Test for improving the estimation
      of premorbid verbal intelligence in older persons with dementia.
AB  - OBJECTIVES: The Cambridge Contextual Reading Test (CCRT), which sets the NART
      words within semantic and syntactic context, has been shown to yield a higher
      prediction of premorbid intelligence than the National Adult Reading Test (NART)
      for patients with mild/moderate dementia (Beardsall & Huppert, 1994). This study
      validates and standardizes the CCRT in a sample of healthy older persons. DESIGN:
      The CCRT was validated against WAIS-R verbal IQ (VIQ) and the Mill Hill
      Vocabulary Test (MHVT). Regression equations were used to compare predictions of
      WAIS-R VIQ from CCRT and demographic variables. A conversion table was
      constructed for predicted VIQ from the equation derived from CCRT scores.
      METHODS: Seventy-three healthy British older persons aged over 70 years completed
      the CCRT, NART, WAIS-R verbal subtests and MHVT. RESULTS: The benefit of context
      was greatest for those with lowest word reading ability. The CCRT was
      satisfactorily correlated with VIQ and the MHVT. Whereas the regression equation
      predicting VIQ using CCRT alone accounted for 61 per cent of the variance, 68 per
      cent was accounted for when demographic variables were included. CONCLUSIONS: The
      CCRT is a valid measure of verbal ability for older persons. When accurate
      information about years of full-time education is available, prediction of verbal
      intelligence should be made combining CCRT with demographic variables. Otherwise,
      prediction should be made using CCRT alone. The CCRT may be used in preference to
      NART in neuropsychological batteries with older persons provided caution is
      exercised when language difficulties are indicated.

PMID- 9631209
TI  - Assessment of treatment outcome in depressed patients: concordance of methods.
AB  - Authors who compared the use of various depression scales for monitoring the
      effects of treatment have reported that the observed pattern of improvement
      depends on the scale used. The discrepancies have generally been attributed to
      interscale differences in content and administration mode. We investigated this
      phenomenon in a group of 52 out-patients with non-psychotic, non-melancholic DSM
      III major depression disorders using three widely employed depression scales in
      both their usual formats and in formats for the alternative mode of
      administration. The six instruments were applied at admission and after 12 and 24
      weeks' treatment. The results suggest that differences between the contents of
      different scales lead to differences in the global improvement reflected, but
      provide no evidence of significant discrepancy between the patterns of
      interviewer-rated and self-rated progress.

PMID- 9631211
TI  - Doping control in professional football.

PMID- 9631212
TI  - Melatonin and jet lag.

PMID- 9631213
TI  - Melatonin: a position statement of the British Olympic Association.

PMID- 9631214
TI  - Circadian rhythms, athletic performance, and jet lag.
AB  - Rapid air travel across several time zones exposes the traveller to a shift in
      his/her internal biological clock. The result is a transient desynchronisation of
      the circadian rhythm, called jet lag, lasting until the rhythm is rephased to the
      new environmental conditions. The most commonly experienced symptoms are sleep
      disorders, difficulties with concentrating, irritability, depression, fatigue,
      disorientation, loss of appetite, and gastrointestinal disturbance. Apart from
      the decrements in mental and physical performance directly consequent on such
      symptoms, competitive athletes are also exposed to the additional negative
      consequences of a shift from the optimal circadian window of performance. A brief
      summary of the possible negative effects of jet lag on athletic performance and
      potentially alleviating strategies is given.

PMID- 9631215
TI  - Fatigue and underperformance in athletes: the overtraining syndrome.
AB  - The overtraining syndrome affects mainly endurance athletes. It is a condition of
      chronic fatigue, underperformance, and an increased vulnerability to infection
      leading to recurrent infections. It is not yet known exactly how the stress of
      hard training and competition leads to the observed spectrum of symptoms.
      Psychological, endocrinogical, physiological, and immunological factors all play
      a role in the failure to recover from exercise. Careful monitoring of athletes
      and their response to training may help to prevent the overtraining syndrome.
      With a very careful exercise regimen and regeneration strategies, symptoms
      normally resolve in 6-12 weeks but may continue much longer or recur if athletes
      return to hard training too soon.

PMID- 9631217
TI  - Early assessment of exercise induced skeletal muscle injury using plasma fatty
      acid binding protein.
AB  - OBJECTIVE: To test whether fatty acid binding protein (FABP) is a useful plasma
      marker for the early detection of exercise induced skeletal muscle injury in
      healthy subjects. METHODS: Plasma concentrations of FABP and myoglobin (Mb) were
      measured in six healthy physical education teacher trainees after 20 minutes of
      downhill running (16% incline; mean lactate 4 mmol/l; 70% (VO2MAX). Creatine
      kinase (CK) was measured for comparison. RESULTS: Significant increases were
      found in plasma FABP (mean peak level 50 micrograms/l), Mb (823 micrograms/l),
      and CK (491 U/l). Mb and FABP concentrations were already significantly elevated
      (p < 0.05) at 30 minutes, but CK not until two hours after exercise. Whereas Mb
      and FABP decreased to normal levels within 24 hours, CK activity remained
      elevated until 48 hours. The Mb to FABP ratio in plasma after exercise induced
      muscle injury was 15.0 (1.3) (mean (SEM)) (range 7.4-31.1), which is within the
      range of ratios calculated for skeletal muscle tissue contents of Mb and FABP,
      but different from the reported plasma ratio after myocardial injury (4-6).
      CONCLUSIONS: After eccentric exercise induced muscle injury, plasma FABP and Mb
      increase and decrease more rapidly than CK, indicating that both FABP and Mb are
      more useful than CK for the early detection of such injuries and the monitoring
      of injury during repeated exercise bouts. In addition, the Mb to FABP ratio in
      the plasma identifies the type of muscle injured.

PMID- 9631216
TI  - Physical exercise and psychological well being: a critical review.
AB  - The relation between physical exercise and psychological health has increasingly
      come under the spotlight over recent years. While the message emanating from
      physiological research has extolled the general advantages of exercise in terms
      of physical health, the equivalent psychological literature has revealed a more
      complex relation. The paper outlines the research evidence, focusing on the
      relation between physical exercise and depression, anxiety, stress responsivity,
      mood state, self esteem, premenstrual syndrome, and body image. Consideration is
      also given to the phenomena of exercise addiction and withdrawal, and
      implications for exercise prescription are discussed.

PMID- 9631218
TI  - Occurrence of exercise induced bronchospasm in elite runners: dependence on atopy
      and exposure to cold air and pollen.
AB  - OBJECTIVES: To study factors affecting the occurrence of exercise induced
      bronchospasm (EIB) in elite runners. METHODS: Fifty eight elite runners, 79% of
      them belonging to Finnish national teams, volunteered. The athletes answered a
      questionnaire on respiratory symptoms. Skin prick tests were used to investigate
      atopy, and spirometry to examine lung function at rest and after an exercise
      challenge test (ECT) at subzero temperature in the winter and after a similar ECT
      in the summer at the end of the birch pollen season. RESULTS: Definitive EIB (a
      post-exercise reduction of 10% or more in forced expiratory volume in one second
      (FEV1) was observed in five (9%) of the 58 runners. A subgroup consisting of 19
      non-atopic symptom-free runners with no family history of asthma was used to
      establish a normal range for post-exercise reduction in FEV1. When this group's
      mean exercise induced change in FEV1 minus 2 SDs (a reduction of 6.5% or more in
      FEV1) was taken as the lower limit of the reference range, 15 (26%) of the
      runners had probable EIB in either the winter or the pollen season. The
      occurrence of probable EIB depended on atopy (odds ratio increased with number of
      positive skin prick test reactions, p < 0.05). Nine (22%) of the 41 runners,
      challenged in both the winter and the pollen season, had probable EIB only in the
      winter, and three (7%) had it only in the pollen season. Only one runner (2%) had
      EIB in both tests. CONCLUSIONS: Mild EIB is common in Finnish elite runners and
      is strongly associated with atopy. Seasonal variability affects the occurrence of
      EIB, and thus exercise testing should be performed in both cold winter air and
      the pollen season to detect EIB in elite runners.

PMID- 9631219
TI  - Knee joint function and the energy cost of level walking in soccer players.
AB  - OBJECTIVES: To study self reported knee joint problems and the energy costs of
      level walking in soccer players. METHODS: Seventeen soccer players and twelve
      control subjects between 18 and 27 years old participated in the study. A
      questionnaire was used to establish the amount of participation in soccer and the
      frequency and extent of knee injuries. The physiological cost index (PCI) was
      used as an index of the energy costs of level walking. RESULTS: Soccer players
      had a significantly higher PCI than control subjects (p = 0.0001). Control
      subjects had a mean (SD) PCI of 0.23 (0.06) beats/m and soccer players had a mean
      PCI of 0.42 (0.12) beats/m. Some 82% of the soccer players experienced knee joint
      problems, whereas only 25% of the control group had problems. CONCLUSIONS: This
      study shows that college soccer players have a higher rate of self reported knee
      problems and higher energy costs of level walking than people who do not play
      soccer.

PMID- 9631221
TI  - A preliminary assessment of professional footballers' awareness of injury
      prevention strategies.
AB  - Players from five English professional football clubs completed a questionnaire
      containing 52 items relating to injury prevention practices and advice received
      on these issues. Responses were received from 55 players, which represents a mean
      response of 11 (4) and a response rate of 38 (14)% from each club (means (SD)).
      The main deficiencies in awareness of injury prevention strategies for players
      were identified as: use of shin pads during training, carbohydrate intake before
      and after training and after matches, cool downs after training and matches, and
      flexibility work. These deficiencies indicate a need for wider education of
      players in current injury prevention strategies.

PMID- 9631220
TI  - Groin pain associated with ultrasound finding of inguinal canal posterior wall
      deficiency in Australian Rules footballers.
AB  - OBJECTIVES: To investigate the prevalence of inguinal canal posterior wall
      deficiency (sports hernia) in professional Australian Rules footballers using an
      ultrasound technique and correlate the results with the clinical symptom of groin
      pain. METHODS: Thirty five professional Australian footballers with and without
      groin pain were investigated blind with a dynamic high resolution ultrasound
      technique for presence of posterior wall deficiency. RESULTS: Fourteen players
      had a history of significant recent groin pain and ten of these were found to
      have bilateral inguinal canal posterior wall deficiency (p < 0.01). The relative
      risk for a history of groin pain with bilateral deficiency was 8.0 (95%
      confidence interval 1.73 to 37.1). Groin pain was also found to be associated
      with increasing age (p < 0.01) which was an independent risk factor. Surgical,
      clinical, and ultrasound follow up for players who underwent hernia repair
      confirmed the validity of ultrasound as a diagnostic tool. CONCLUSIONS: Dynamic
      ultrasound examination is able to detect inguinal canal posterior wall deficiency
      in young males with no clinical signs of hernia. This condition is very prevalent
      in professional Australian Rules footballers, including some who are
      asymptomatic. There was a correlation between bilateral deficiency and groin
      pain, although the temporal relationship between the clinical and ultrasound
      findings is not established by the current study. Ultrasound shows promise as a
      diagnostic tool in athletes with chronic groin pain who are considered possible
      candidates for hernia repair.

PMID- 9631222
TI  - Effects of seasonal change in rugby league on the incidence of injury.
AB  - OBJECTIVES: To assess the effects that the recent seasonal change in rugby league
      from winter to summer has had on the incidence of injury. METHODS: All injuries
      that occurred during games and training were recorded throughout four consecutive
      seasons (three winter, one summer) for the first team squad of a British
      professional rugby league club. Data included nature of injury, days lost as the
      result of injury, player position, month, and season. RESULTS: An increasing
      incidence of injury over the four seasons was observed, with the summer seasons
      having an incidence almost double that of the first winter season recorded (696.8
      per 1000 hours and 363.55 per 1000 hours respectively). The severity of injury
      was shown to decline over the four seasons. Most injuries were incurred in
      matches (74.9%) rather than during training (25.1%). CONCLUSIONS: The findings
      show an increasing incidence of injury in summer rugby but with decreased
      severity. It is not known if this is the result of playing back to back rugby
      seasons or is a consequence of a change in playing season and ground conditions.

PMID- 9631223
TI  - Injury in summer rugby league football: the experiences of one club.
AB  - OBJECTIVE: To investigate whether the movement of the playing season from winter
      to summer would alter the risk of injury to players taking part in first team
      European professional rugby league. METHODS: The study design was a historical
      cohort design comparing winter and summer seasons in first team European rugby
      league, which recorded injuries received by players during match play. Each
      injury was classified according to site, type, player position, activity at the
      time of injury, and time off as a result of injury. RESULTS: The risk of injury
      when playing summer rugby league was higher than when playing winter rugby league
      (relative risk = 1.67 (95% confidence interval 1.18 to 2.17)). Both forwards
      (1.08 (0.28 to 1.88)) and backs (2.36 (2.03 to 2.69)) experienced an increased
      risk of injury. CONCLUSIONS: Summer rugby may have resulted in a shift of injury
      risk factors as exhibited by a change in injury patterns. This may be due to
      playing conditions, but there were also some law changes. Changes in playing
      style, team tactics, player equipment, fitness preparation, and the reduced
      preseason break may also have had confounding effects on injury risk.

PMID- 9631224
TI  - An outbreak of methicillin resistant Staphylococcus aureus infection in a rugby
      football team.
AB  - Outbreaks of infection caused by methicillin resistant Staphylococcus aureus are
      common in hospitals and nursing homes, but until now none have been reported in
      the community. This is a report of an outbreak involving five members of a rugby
      football team.

PMID- 9631225
TI  - What do adult squash players think about protective eyewear?
AB  - OBJECTIVE: To determine the attitudes of adult squash players towards protective
      eyewear. METHODS: A survey of 197 competition and social squash players from
      seven squash centres in the outer eastern suburbs of Melbourne, Australia was
      conducted in September to October 1995. Information about participation in
      squash, previous injuries, use of protective eyewear, barriers towards eyewear
      use, and attitudes towards protective eyewear was obtained by a self report
      questionnaire. RESULTS: Squash is a popular sport in Australia. Of the players
      surveyed, 6% played in junior competitions, 67% in senior competitions, and 27%
      were social players. Most had been playing for more than ten years. Some 15% of
      players had previously suffered an eye injury, most commonly caused by a racquet.
      Less than 10% of players reported that they wore protective eyewear when they
      played squash, and 35% of these wore prescriptive lenses which they considered to
      be protective. The major reason for not wearing protective eyewear was the
      perception that it was unnecessary. Poor vision and a lack of comfort were also
      stated as reasons by a significant number of players. More than half (57%) of the
      respondents agreed that more players should wear protective eyewear, yet only 16%
      thought it should be compulsory for all players. There was considerable support
      for protective eyewear use by junior players, however. CONCLUSIONS: The rate of
      protective eyewear use is low among competition and social squash players in
      Melbourne. The major areas that need to be addressed are the ignorance of the
      need for protective eyewear among social and experienced players and the mistaken
      belief that prescription lenses provide adequate protection on a squash court.

PMID- 9631226
TI  - Can the effects of exercise on bone quality be detected using the CUBA clinical
      ultrasound system?
AB  - OBJECTIVES: To determine whether the CUBA clinical quantitative ultrasound bone
      analyser was able to distinguish variations in bone quality between groups
      categorised according to activity level. METHOD: Eighty one white women aged 32
      to 89 completed a confidential questionnaire on general health, diet, and
      exercise participation and underwent ultrasound testing at the right calcaneus
      utilising a CUBA clinical ultrasound system. RESULTS: The results confirmed the
      inverse relationship between age and the ultrasound indicators of bone quality:
      broadband ultrasound attenuation (BUA) (r = -0.52) and velocity of sound (VOS) (r
      = -0.68). Subject height weakly but significantly correlated with BUA (r = 0.39)
      and VOS (r = 0.35), and subject weight only correlated significantly with BUA (r
      = 0.37). Activity level was significantly associated (p < 0.05) with the changes
      in ultrasound attenuation (BUA). The use of hormone replacement therapy or the
      contraceptive pill, a family history of osteoporosis, and gross indicators of
      calcium consumption did not yield significant results. CONCLUSION: Data obtained
      from the CUBA clinical system were sensitive enough to allow women to be
      classified into groups according to activity level. These data were within the
      range of "normal" ultrasound data and hence it is suggested that the machine has
      research as well as clinical value.

PMID- 9631227
TI  - Relation between bone turnover, oestradiol, and energy balance in women distance
      runners.
AB  - OBJECTIVE: To explore relations between biochemical markers of bone turnover,
      indices of nutritional status, and serum oestradiol concentration in women
      distance runners. METHODS: Thirty three women distance runners of mean age (SD)
      27.2 (1.8) years participated. Eighteen were defined as eumenorrhoeic, nine as
      amenorrhoeic, and six as oligomenorrhoeic. Mean (SD) running distance was 47.6
      (22.4) km/week. Using bivariate correlation and regression analysis, serum levels
      of osteocalcin and bone alkaline phosphatase (BAP) and also urine
      deoxypyridinoline/creatinine (Dpyr/Cr) were correlated with mean daily energy
      balance, body mass index (BMI; kg/m2), and serum levels of total 3,5,3'
      triiodothyronine and oestradiol within each group by menstrual status. RESULTS:
      All the amenorrhoeic women were in negative energy balance; they had a lower BMI,
      lower serum levels of oestradiol, triiodothyronine, osteocalcin and BAP and a
      lower urine Dpyr/Cr than any of the oligomenorrhoeic or eumenorrhoeic women.
      These variables were also lower in oligomenorrhoeic than in eumenorrhoeic women.
      Positive correlations were observed between serum levels of osteocalcin or BAP
      and both BMI and serum oestradiol concentration in amenorrhoeic, but not in
      oligomenorrhoeic or eumenorrhoeic women. Urine Dpyr/Cr did not correlate with any
      other variable within any group. Serum oestradiol concentration correlated
      positively with BMI in amenorrhoeic and oligomenorrhoeic, but not eumenorrhoeic
      women. CONCLUSIONS: Positive correlations between serum levels of bone formation
      markers, BMI and serum oestradiol concentration in our amenorrhoeic runners
      suggested that their reduced bone formation was linked to a low BMI and an
      oestrogen deficiency. Reduced bone turnover in amenorrhoeic distance runners has
      not previously been shown. These findings emphasise the importance of body mass
      and its possible link with a chronic energy deficit and hypothalamic dysfunction
      on bone remodelling balance in amenorrhoeic runners.

PMID- 9631228
TI  - Recurrent dislocation of the extensor carpi ulnaris tendon.
AB  - Five patients with recurrent dislocation of the extensor carpi ulnaris (ECU)
      tendon resulting from an athletic injury were treated by reconstruction of the
      ECU tendon sheath, and each had a satisfactory result. Two types of disruption of
      the fibro-osseous sheath were found. In two cases in which the fibro-osseous
      sheath ruptured radially, the torn sheath lay on its ulnar groove beneath the ECU
      tendon. These patients were treated by direct suture of the sheath over the ECU
      tendon. In three cases in which the fibro-osseous sheath ruptured ulnarly, the
      torn sheath lay superficial to the ECU tendon. These patients were treated by
      reconstruction of the sheath using a piece of the extensor retinaculum. We
      believe that surgical reconstruction of the fibro-oseous sheath of the ECU tendon
      should be considered for symptomatic dislocation of the ECU tendon, even in an
      acute case.

PMID- 9631229
TI  - Achilles tendon rupture and sciatica: a possible correlation.
AB  - The association between Achilles tendon rupture and sciatica was investigated by
      questionnaire in 138 patients who underwent repair of an Achilles tendon rupture,
      and in a group of individuals nominated by the patients, matched for age, sex,
      and occupation. A total of 102 patients (74%) and 128 peer nominated controls
      (71%) replied to the questionnaire. Of the 102 respondent patients, 18 had an
      officebased job, 47 were involved in skilled nonmanual work, and 16 were retired.
      Back pain had been experienced by 63 of the patients who replied to the
      questionnaire, and by 91 (75%) of the individuals in the control group
      (difference not significant). In about 30% of both groups, the pain confined them
      to bed for at least two days, and resulted in absence from work. Thirteen of the
      patients and 16 of the controls had undergone thoracic, lumbar, or sacral
      radiography. One individual in each group had received surgery for back pain.
      However, 35 of 102 patients had experienced sciatic pain before Achilles tendon
      rupture. Pain of a similar nature had been experienced by only 15 individuals in
      the control group (12%) (p < 0.001). Using this study design, we found a highly
      significant association between Achilles tendon rupture and sciatica. We propose
      that this association could be due to impaired afferent signals from the lower
      leg, or to similar collagen or vascular anomalies of the vertebral disc and the
      Achilles tendon.

PMID- 9631230
TI  - Spontaneous rupture of extensor pollicis longus tendon in a kick boxer.
AB  - A 23 year old male kick boxer presented with a 24 hour history of pain and being
      unable to extend the interphalangeal joint of the left thumb. There was no
      history of trauma or any other risk factor for spontaneous rupture of the
      extensor pollicis longus tendon. On the previous day, he had been doing reverse
      press ups on the dorsum of his hands with his wrists hyperflexed as part of his
      training for kick boxing. At operation the extensor pollicis longus tendon was
      found to be divided at the level of the dorsal tubercle of the radius and was not
      directly repairable. The treatment was an extensor indicis proprius transfer. We
      suggest that the cause of the tendon rupture was direct pressure on the dorsal
      tubercle of the radius sustained while performing reverse press ups.

PMID- 9631231
TI  - Diagnostic pitfalls in sports related laryngeal injury.
AB  - The serious nature of laryngeal trauma sustained during sporting activity can be
      easily overlooked. Concomitant injury should not distract from the diagnosis of
      potential airway problems. The effects of head and neck trauma on the airway may
      be delayed. The assessment and management of a patient with suspected laryngeal
      injury should be carried out by experienced medical practitioners.

PMID- 9631232
TI  - Chronic groin pain in an athlete: an unusual presentation.
AB  - Persistent disabling groin pain in an active sportsman is a frustrating
      diagnostic and management problem for both the athlete and physician. After
      clinical examination and investigation there remains a group of patients who have
      unexplained groin pain, and may undergo lengthy periods of conservative
      management with numerous radiological investigations. Here we highlight such a
      case.

PMID- 9631233
TI  - Walking to health.

PMID- 9631234
TI  - Subcutaneous rupture of the Achilles tendon.

PMID- 9631236
TI  - Signaling role of PDE isozymes in pathobiology of glomerular mesangial cells.
      Studies in vitro and in vivo.
AB  - Mesangial cells (MC) of renal glomeruli respond to immune-inflammatory injury by
      accelerated proliferation and generation of reactive oxygen metabolites (ROM). We
      studied in vivo and in vitro roles of cAMP-protein kinase A (PKA) signaling in
      modulation of these pathobiologic processes with focus on PDE isozymes. Mitogenic
      synthesis of DNA in mesangial cells grown in primary culture was blocked by
      forskolin and dibutyryl cyAMP. Incubation of MC with PDE-3 inhibitors,
      cilostamide and lixazinone, inhibited (> 50%) mitogenesis, whereas inhibitors of
      PDE-4, rolipram and denbufylline, caused little or no inhibition. Conversely,
      inhibitors of PDE-4 suppressed generation of ROM in MC, whereas inhibitors of PDE
      3 had no effect. Incubation of mesangial cells with cilostamide or with rolipram
      increased in situ activity of PKA, and effects of the two inhibitors were
      additive. PDE inhibitors also decreased activity of mitogen-activated protein
      kinase. The efficacy of PDE isozyme inhibitors (IC50) to suppress mitogenesis or
      ROM generation paralleled IC50 for inhibition of cAMP hydrolysis by extracts from
      mesangial cells. Administration of lixazinone or lixazinone in combination with
      rolipram to rats with mesangial proliferative glomerulonephritis induced by
      antithymic serum suppressed proliferation of mesangial cells and also reduced
      other histopathologic manifestations of the disease. Based on these observations,
      we propose that in MC, a cAMP pool that is hydrolyzed by PDE-3 inhibits by
      negative crosstalk via activation of PKA, mitogen-activated protein kinase (MAPK)
      pathway, and mitogenesis; whereas cAMP pool linked to PDE-4 inhibits, also via
      activation of PKA, ROM generation in mesangial cells. Results also suggest that
      PDE isozyme inhibitors, in particular inhibitors of PDE-3, should be investigated
      for potential use for "signal transduction pharmacotherapy" of
      glomerulonephritis.

PMID- 9631235
TI  - Regulation of PDE-4 cAMP phosphodiesterases by phosphatidic acid.
AB  - Phosphatidic acid (PA) has been previously shown to activate specifically some of
      the isoforms of type 4 cylic nucleotide phosphodiesterases (PDE-4) in an
      acellular system. In the present work, we have investigated the mechanism of PA
      activating effect by using a recombinant PA-sensitive isoform, PDE-4D3. The
      enzyme was specifically activated by acidic phospholipids, but not by
      zwitterionic phospholipids or anionic detergents. The importance of the role of
      PA acidic groups in the activation process was confirmed by studying the
      influence of pH and ionic strength on activation. Crosslinking experiments
      suggested that PA might influence the ability of PDE-4D3 to form dimers. Binding
      studies performed with radiolabeled PA showed that PA binds to a PDE-4D3
      preparation in a saturable manner. Specifically bound PA was displaced by
      anionic, but not by zwitterionic phospholipids. With a preparation of PDE-4B2, a
      PDE-4 isoform insensitive to PA activation, PA binding was only displaced by high
      concentrations of unlabeled PA, suggesting that high-affinity PA binding sites
      are only present on PDE-4D3. These data support the hypothesis that PA-activating
      effect depends on direct binding of the effector on specific sites carried by the
      PDE-4D3 protein.

PMID- 9631237
TI  - Cyclic nucleotide-mediated regulation of vascular smooth muscle cell cyclic
      nucleotide phosphodiesterase activity. Selective effect of cyclic AMP.
AB  - Cultured rat aortic vascular smooth muscle cells (VSMC) express both cGMP-
      inhibited cAMP phosphodiesterase (PDE-3) and Ro,20-1724-inhibited cAMP
      phosphodiesterase (PDE-4) activities. Utilizing a PDE-3-selective inhibitor
      (cilostamide) and a PDE-4-selective inhibitor (Ro,20-1724), PDE-3 and PDE-4
      activities were shown to account for 15 and 55% of total VSMC cAMP
      phosphodiesterase (PDE) activity. Incubations of VSMC with either forskolin or 8
      bromo-cAMP caused a concentration- and time-dependent increase in total cellular
      cAMP PDE activity. In these cells, both PDE-3 and PDE-4 activities were
      increased, with a relatively larger effect observed on PDE-3 activity. Similar
      incubations with an activator of soluble guanylyl cyclase (sodium nitroprusside)
      or with 8-bromo-cGMP did not increase cAMP PDE activity. cAMP-induced increases
      in cAMP PDE activity were inhibited with actinomycin D or cycloheximide,
      demonstrating that new mRNA and protein synthesis were required. We conclude that
      VSMC cAMP PDE activity is elevated following long-term elevation of cAMP, and
      that increases in PDE-3 and PDE-4 activities account for more than 70% of this
      increase. These results may have implications for long-term use of cAMP PDE
      inhibitors as therapeutic agents.

PMID- 9631238
TI  - Cyclic nucleotide PDE-3. Quantitation of PDE-3A and -3B mRNAs in rat tissues by
      RNase protection assay.
AB  - Type 3 cyclic nucleotide phosphodiesterase (PDE-3) isoforms exhibit a high
      affinity ("low K(m)") for cAMP and are specifically inhibited by cGMP and a
      number of pharmacological agents, which increase myocardial contractility,
      inhibit platelet aggregation, and increase smooth muscle relaxation. The PDE-3
      family consists of at least two isozymes, PDE-3A (cardiac type) and PDE-3B
      (adipocyte type), with distinct tissue-specific distributions. PDE-3A mRNA is
      highly expressed in the cardiovascular system, whereas PDE-3B mRNA is primarily
      expressed in adipocytes and hepatocytes. Toward understanding potential roles of
      PDE-3 in diabetes mellitus, we have established a specific and sensitive RNase
      protection assay (RPA) for quantitating PDE-3A and PDE-3B mRNA in rat diabetic
      models. In fatty Zucker diabetic (ZDF) rats, PDE-3A mRNA, but not PDE-3B mRNA,
      was expressed in heart, whereas liver and white and brown fat tissues
      predominantly expressed PDE-3B mRNA. Unexpectedly, PDE-3B mRNA expression was
      approximately 2.5 times higher than PDE-3A mRNA in aorta from both ZDF and
      Sprague-Dawley (SD) rats. In contrast, expression levels of PDE-3A mRNA in heart
      were similar in both species. With this RPA, we were thus able to compare PDE-3A
      and -3B mRNA levels in different tissues as well as in different rat species.

PMID- 9631239
TI  - Downregulation of right ventricular phosphodiesterase PDE-3A mRNA and protein
      before the development of canine heart failure.
AB  - Phosphodiesterase III (PDE-3) inhibitors are inotropes used to treat congestive
      heart failure (HF). Previous studies showed PDE-3A mRNA levels were reduced in
      the left ventricle (LV) in dogs subjected to pacing-induced HF. The present study
      evaluated a time-course for RV-specific changes in PDE-3A mRNAs and proteins
      after pacing for 3 wk (n = 4) or in HF (4-5 wk; n = 4-6). Total RNA from LV/RV
      tissues was isolated for Northern analyses; cytosolic and microsomal proteins
      were prepared for PDE-3A immunoblots. PDE-3A mRNAs (7-8 and 10 kb) were
      normalized against glyceraldehyde-3-phosphodehydrogenase (GAPDH) or ribosomal 18s
      with similar results. PDE-3A/GAPDH ratios in 3 wk were unchanged in LV, but
      significantly (p < 0.05) reduced by 48% in RV vs unpaced controls (n = 8). In
      contrast, PDE-3A (7-8 kb)/GAPDH ratios were significantly reduced in HF by 50-59%
      in both ventricles. Consistent with mRNA levels, significant reductions in
      microsomal 135 kDa (93-96%) and cytosolic 120 kDa PDE-3A (57-69%) were seen in
      both ventricles in HF or in the RV at 3 wk; an LV-specific reduction (50%) in
      cytosolic 80 kDa PDE-3A in HF was also detected. In summary, RV-specific
      downregulation of PDE-3A mRNA/protein(s) at 3 wk suggests that hemodynamic rather
      than humoral mechanisms are responsible, and provides a molecular basis for the
      limited efficacy of milrinone in the progression of HF.

PMID- 9631240
TI  - Expression and characterization of deletion recombinants of two cGMP-inhibited
      cyclic nucleotide phosphodiesterases (PDE-3).
AB  - cDNAs encoding two PDE-3 or cyclic GMP-inhibited (cGI) cyclic nucleotide
      phosphodiesterase (PDE) isoforms, RPDE-3B (RcGIP1) and HPDE-3A (HcGIP2), were
      cloned from rat (R) adipose tissue and human (H) heart cDNA libraries. Deletion
      and N- and C-terminal truncation mutants were expressed in Escherichia coli in
      order to define their catalytic core. Active mutants of both RPDE-3B and HPDE-3A
      included the domain conserved among all PDEs plus additional upstream and
      downstream sequences. An RPDE-3B mutant consisting of the conserved domain alone
      and one from which the RPDE-3B 44-amino acid insertion was deleted exhibited
      little or no activity. All active recombinants exhibited a high affinity (< 1
      microM) for cyclic AMP (cAMP) and cyclic GMP (cGMP), were inhibited by cAMP,
      cGMP, and cilostamide, but not by rolipram, and were photolabeled with [32P]
      cGMP. The IC50 values for cGMP inhibition of cAMP hydrolysis were lower for HPDE
      3A than for RPDE-3B recombinants. The deduced amino acid sequences of HPDE-3A and
      RPDE-3B catalytic domains are very similar except for the 44-amino acid insertion
      not found in other PDEs. It is possible that this insertion may not only
      distinguish PDE-3 catalytic domains from other PDEs and identify catalytic
      domains of PDE-3 subfamilies or conserved members of the PDE-3 gene family, but
      may also be involved in the regulation of sensitivity of PDE-3s to cGMP.

PMID- 9631241
TI  - CDP840: a novel inhibitor of PDE-4.
AB  - We present the in vitro characterization of a novel phosphodiesterase type 4
      inhibitor, CDP840 (R-[+]-4-[2-?3-cyclopentyloxy-4-methoxyphenyl?-2
      phenylethyl]pyridine), which has shown efficacy in a phase II allergen challenge
      study in asthmatics without adverse effects. CDP840 potently inhibits PDE-4
      isoenzymes (IC50 2-30 nM) without any effect on PDE-1, 2, 3, 5, and 7 (IC50 > 100
      microM). It exhibited no significant selectivity in inhibiting human recombinant
      isoenzymes PDE-4A, B, C or D and was equally active against the isoenzymes
      lacking UCR1 (PDE-4B2 and PDE-4D2). In contrast to rolipram, CDP840 acted as a
      simple competitive inhibitor of all PDE-4 isoenzymes. Studies with rolipram
      indicated a heterogeneity within all the preparations of PDE-4 isoenzymes,
      indicative of rolipram inhibiting the catalytic activity of PDE-4 with both a low
      or high affinity. These observations were confirmed by the use of a PDE-4A
      variant, PDE-4A330-886, which rolipram inhibited with low affinity (IC50 = 1022
      nM). CDP840 in contrast inhibited this PDE-4A variant with similar potency (IC50
      = 3.9 nM), which was in good agreement with the Kd of 4.8 nM obtained from [3H]
      CDP840 binding studies. Both CDP840 and rolipram inhibited the high-affinity
      binding of [3H]-rolipram binding to PDE-4A, B, C, and D with similar Kd app (7-19
      nM and 3-5 nM, respectively). Thus, the activity of CDP840 at the [3H]-rolipram
      binding site was in agreement with the inhibitor's activity at the catalytic
      site. However, rolipram was approximately 100-fold more potent than CDP840 at
      inhibiting the binding of [3H]-rolipram to mouse brain in vivo. These data
      clearly demonstrate that CDP840 is a potent selective inhibitor of all PDE-4
      isoenzymes. In contrast to rolipram, CDP840 was well-tolerated in humans. This
      difference, however, cannot at present be attributed to either isoenzyme
      selectivity or lack of activity in vitro at the high-affinity rolipram binding
      site (Sr).

PMID- 9631242
TI  - The gamma-subunit of the rod photoreceptor cGMP-binding cGMP-specific PDE is
      expressed in mouse lung.
AB  - The type 6 phosphodiesterase (PDE-6) from retinal rod photoreceptors is an alpha
      beta gamma 2 heterotetramer. The alpha- and beta-subunits contain catalytic sites
      for cGMP hydrolysis, whereas the gamma-subunits (P gamma) serve as a protein
      inhibitor of the enzyme. P gamma is believed to be expressed only in
      photoreceptors. Using RT-PCR, we have amplified the complete coding sequence for
      P gamma from mouse lung RNA. The expression of P gamma in this tissue may be
      related to its ability to interact the type 5 phosphodiesterase (PDE-5), which is
      the predominant cGMP binding protein in lung. We therefore suggest that P gamma
      may have a wider signaling role in mammalian cells than previously appreciated.

PMID- 9631243
TI  - A photoaffinity probe covalently modifies the catalytic site of the cGMP-binding
      cGMP-specific phosphodiesterase (PDE-5).
AB  - The cGMP-binding cGMP-specific phosphodiesterase (PDE-5) contains distinct
      catalytic and allosteric binding sites, and each is cGMP-specific. Cyclic
      nucleotide phosphodiesterase inhibitors, such as 3-isobutyl-1-methylxanthine
      (IBMX), are believed to compete with cyclic nucleotides at the catalytic sites of
      these enzymes, but the portion of PDE-5 that accounts for interaction of either
      of these inhibitors of the substrates themselves with the catalytic domain of the
      enzymes has not been identified. IBMX was derivatized to yield the photoaffinity
      probe 8([3-125I,-4-azido]-benzyl)-IBMX, which is referred to as 8(125IAB)-IBMX.
      This probe was incubated with partially purified recombinant bovine PDE-5. After
      UV irradiation and SDS-PAGE, a single radiolabeled band that coincided with the
      position of PDE-5 was visualized on the gel, and the photoaffinity labeling of
      PDE-5 was linear with increasing concentration of the 8(125IAB)-IBMX. Prominent
      Coomassie blue-stained bands other than PDE-5 were not labeled significantly. The
      photoaffinity labeling was progressively blocked by cGMP at concentrations higher
      than 10 microM, whereas cAMP or 5'-GMP exhibited only weak inhibitory effects.
      Other compounds that are believed to interact with the PDE-5 catalytic site,
      including IBMX, cIMP, and beta-phenyl-1,N2-etheno-cGMP (PET-cGMP), also inhibited
      the photoaffinity labeling in a concentration-dependent manner. The IC50 of PET
      cGMP for inhibition of photoaffinity labeling was 10 microM, which compared
      favorably with an IC50 of 5 microM for inhibition of PDE-5 catalytic activity by
      this compound. It is concluded that the interaction of this photoaffinity probe
      with PDE-5 is highly specific for the catalytic site over the allosteric binding
      sites of PDE-5 and could prove useful in studies to map the catalytic site of PDE
      5.

PMID- 9631244
TI  - Characterization of CHO-K1 cells stably expressing PDE-IV enzymes. Whole-cell
      cAMP determinations vs broken-cell enzymatic assays.
AB  - A CHO-K1 cell line stably expressing a recombinant full-length human PDE-IVa
      (HSPDE4A4B) enzyme was established under hygromycin B selection. Full-length
      expression of the protein was determined by Western blot analysis, which revealed
      the presence of a 125-kDa immunoreactive band using rabbit anti-PDE-IVa
      antibodies. The potency of inhibitor compounds was examined by their ability to
      increase cAMP in the whole-cell, and by their ability to inhibit cAMP hydrolysis
      in a 100,000 g supernatant (soluble enzyme preparation) obtained from the same
      cell line. Inhibition of the expressed PDE-IVa activity by selective PDE-IV
      inhibitors--(R) and (S)-rolipram, RS 14203, and CDP 840--at 100 nM substrate
      demonstrated that RS 14203 and CDP 840 were the most potent with IC50 = 9 nM,
      followed by (R)-rolipram (IC50 = 110 nM) and (S)-rolipram (IC50 = 420 nM). The
      rank order of potencies of the inhibitors in elevating cAMP in the whole-cell
      assay was quite different from that on the soluble enzyme. RS 14203 was still the
      most potent compound in elevating cAMP. Moreover, the relative rank order of
      potencies between CDP 840 and (R)-rolipram changed dramatically, such that (R)
      rolipram was more potent than CDP 840 = (S)-rolipram. An apparent 30-fold
      stereoselectivity between (R)- and (S)-rolipram was also noted. The whole-cell
      rank order of potencies was also maintained when PKA activity ratios were
      measured in place of cAMP levels. The ability of the compounds to elevate cAMP in
      the stable CHO-K1 cells appeared to track better with the potency of the
      compounds against the high-affinity (Sr) conformer of the enzyme rather than the
      low-affinity catalytic state.

PMID- 9631245
TI  - Interleukin-10 does not mediate the inhibitory effect of PDE-4 inhibitors and
      other cAMP-elevating drugs on lipopolysaccharide-induced tumors necrosis factor
      alpha generation from human peripheral blood monocytes.
AB  - Lipopolysaccharide (LPS)-induced liver injury in mice and LPS-induced tumor
      necrosis factor-alpha (TNF-alpha) generation by murine macrophages and
      hepatocytes are suppressed markedly by agents that elevate intracellular cAMP.
      Phosphodiesterase (PDE)-4 inhibitors, beta 2-adrenoceptor agonists, and E-series
      prostaglandins also attenuate the induction of the TNF-alpha gene in human
      monocytes in response to bacterial LPS. The mechanism of action of cAMP is
      unclear, but in the mouse, is believed to involve the generation of this anti
      inflammatory cytokine, interleukin-10 (IL-10). In this article, we describe the
      results of studies designed to determine the extent to which IL-10 contributes to
      the suppression of TNF-alpha generation from LPS-stimulated human monocytes
      evoked by 8-bromo cyclic AMP (8-Br-cAMP), rolipram, salbutamol, and prostaglandin
      E2 (PGE2). LPS evoked a time- and concentration-dependent generation of TNF-alpha
      (t1/2 = 4.5 h; EC50 = 273 pg/mL), which was inhibited by exogenous human
      recombinant (h) IL-10 (IC50 = 124 pg/mL), and by rolipram (EC50 = 420 nM), 8-Br
      cAMP (EC50 = 77 (microM), PGE2 (EC50 = 15 nM) and salbutamol (EC50 = 20 nM). In
      addition, 8-Br-cAMP, PGE2; and salbutamol (but not rolipram) augmented
      significantly LPS-induced IL-10 production (two-to-fivefold) under identical
      experimental conditions. Pretreatment of monocytes with an anti-IL-10 monoclonal
      antibody (MAb) that abolished the inhibitory action of a maximally effective
      concentration of exogenous hrIL-10, failed to attenuate the inhibitory effect of
      rolipram, PGE2, salbutamol, and 8-Br-cAMP. Anti-IL-10 was similarly inactive when
      the number of monocytes seeded was increased from 0.5 to 4 x 10(6)/mL or when
      measurements were made at 42 h post-LPS, a time when the concentration of IL-10
      released was maximal. Collectively, these data suggest that in contrast to murine
      hepatocytes and macrophages, IL-10 does not mediate the inhibitory effect of cAMP
      elevating drugs on TNF-alpha generation from human monocytes. Although the reason
      for this discrepancy is unclear, we suggest that the influence of cAMP on the
      transcriptional regulation of the TNF-alpha gene differs between species or when
      monocytes have differentiated into macrophages.

PMID- 9631246
TI  - Encopresis was associated with child sexual abuse.

PMID- 9631248
TI  - Child abuse and severity of disturbance among adult psychiatric inpatients.
AB  - OBJECTIVE: The aim of this study was to determine whether childhood abuse is
      related to severity of psychological disturbance in adulthood, even within an
      extremely disturbed, predominantly psychotic, population. METHODOLOGY: The
      medical records of 100 consecutive admissions to an adult psychiatric inpatient
      unit were examined. Documentation of physical or sexual abuse as a child was
      recorded together with several measures of severity of pathology including:
      suicidality, length of current admission, age at first admission and use of
      Intensive Care Unit and Mental Health Act. RESULTS: The study revealed
      relationships between childhood sexual or physical abuse and suicidality,
      duration of hospitalization, and age at first admission. Several gender
      differences in these relationships were found. These included the finding that
      sexually abused males, but not sexually abused females, were significantly more
      suicidal than their nonabused counterparts. CONCLUSIONS: The theoretical and
      clinical implications of further evidence that child abuse is related to the most
      severe levels of dysfunction in adulthood, including psychosis, are discussed.
      The need for routine child abuse inquiry in inpatient settings is reiterated.

PMID- 9631247
TI  - Exposure to interparental violence in childhood and psychosocial adjustment in
      young adulthood.
AB  - OBJECTIVE: To study the relationships between retrospective reports of exposure
      to interparental violence in childhood and rates of psychosocial adjustment
      problems in young adulthood in a birth cohort of New Zealand subjects. METHOD:
      Data were gathered during the course of an 18 year longitudinal study of a birth
      cohort of 1,265 New Zealand children. At age 18 retrospective reports of exposure
      to interparental violence were obtained. At this time the cohort was also
      assessed on measures of psychosocial adjustment including mental health problems,
      substance abuse behaviors, and criminal offending. RESULTS: Young people
      reporting high levels of exposure to interparental violence had elevated rates of
      adjustment problems at age 18. These problems included mental health problems,
      substance abuse behaviors and criminal offending. Analyses using multiple
      logistic regression showed that much of this elevated risk was explained by
      social and contextual factors associated with exposure to interparental violence.
      However, even after adjustment for confounding factors, exposure to father
      initiated violence was associated with increased risks of anxiety, conduct
      disorder and property crime, while exposure to mother initiated violence was
      associated only with increased risks of later alcohol abuse/dependence.
      CONCLUSION: Children exposed to high levels of interparental violence are an at
      risk population for psychosocial adjustment problems in young adulthood. Much of
      the elevated risk of these children arises from the social context within which
      interparental violence occurs. Nonetheless, exposure to interparental violence,
      and particularly father initiated violence, may be associated with later
      increased risks of anxiety, conduct disorder, problems with alcohol, and criminal
      offending.

PMID- 9631249
TI  - The long-term impact of child abuse on religious behavior and spirituality in
      men.
AB  - OBJECTIVE: Two hypotheses were tested: (1) In a sample of adult men, past
      experience of child abuse (sexual, physical, or emotional) will be related to
      higher levels of reported alienation from religion and God as shown in lower
      rates of current religious behavior, higher frequency of spiritual "injury," and
      lower stability of religious behavior and experiences; (2) More "severe" forms of
      abuse will be associated with higher indicators of alienation. METHOD: Data were
      collected from 1,207 male veterans, 527 (43.7%) of whom reported being abused as
      a child. Each subject completed the Spiritual Issues Assessment, a large survey
      which includes data about: (1) KASL Religiosity Index; (2) The Spiritual Injury
      Scale; and (3) Religious items from the Westberg Personal Health Inventory.
      RESULTS: A history of sexual abuse was related to significantly greater spiritual
      injury and lower stability of spiritual behaviors and experiences, but not to
      overall rate of current religious behavior. Surprisingly, abuse was related to
      increased frequency of prayer and of "spiritual experience." Multivariate
      analyses indicate that the effect size is relatively small and the type of abuse
      was less important than the presence of any form of abuse. CONCLUSIONS: The
      findings suggest that the impact of childhood abuse is more complex than
      initially hypothesized. While abuse seems to be related to continuing spiritual
      injury and distress, it is also related to higher levels of some spiritual
      activities and experiences which are usually associated with positive
      spirituality.

PMID- 9631250
TI  - The rate of physical child abuse in Chinese families: a community survey in Hong
      Kong.
AB  - OBJECTIVE: This study aimed to describe the extent and pattern of parental child
      battering in Chinese families in Hong Kong. It was hypothesized that the unique
      feature of filial piety in Chinese culture will create a different pattern of
      child abuse in Hong Kong when compared to Western societies. METHOD: A telephone
      survey of 1,019 households randomly selected from the local residential telephone
      directory was completed. Three hundred and fifty-nine fathers and 660 mothers of
      a child at or under the age of 16 participated in the study. The occurrence of
      child abuse was assessed by the Chinese version of the Conflict Tactics Scale
      (Straus, 1979). RESULTS: The base rate of physical child abuse was 526 per 1,000
      children for minor violence and 461 per 1,000 children for severe violence. Minor
      violence was most likely directed at children aged 3-6 years or children without
      siblings in the family; and committed by mothers, parents aged 19-37 years, or
      housewives/unemployed fathers. The highest rate of severe violence occurred among
      boys or children aged 3-6 years; and was committed by mothers, parents aged 19-37
      years, or housewives/unemployed fathers. Common risk factors of child abuse were
      identified for Chinese and US families. CONCLUSIONS: When compared to US
      families, Chinese families showed slightly lower rates of minor violence but
      higher rates of severe violence toward children. Children aged 3-6 years were the
      most vulnerable victims and female caregivers the most likely abusers in both US
      and Chinese families. Our findings also suggested that it cannot be assumed that
      results based on local official statistics and clinical samples regarding the
      extent of child abuse and characteristics of the victims and abusers can be
      accurately extended to community samples.

PMID- 9631251
TI  - The impact of childhood emotional abuse: an extension of the Child Abuse and
      Trauma Scale.
AB  - OBJECTIVE: There are few well-validated measures of childhood emotional abuse.
      This study explored the potential of the Child Abuse and Trauma Scale (CATS;
      Sanders & Becker-Lausen, 1995) to yield such a measure. The CATS was originally
      devised to measure the extent of adverse sexual, physical and neglectful
      experiences, but contains items that also reflect the construct of emotional
      abuse. METHOD: A sample of 236 nonclinical women completed the CATS and the
      Hospital Anxiety and Depression scale. A fourth subscale was drawn from the
      existing CATS items, reflecting reported emotional abuse during childhood.
      RESULTS: The concurrent validity and internal consistency of this new subscale
      were tested, and were found to be at an acceptable level. Indeed, there was some
      indication that the new childhood emotional abuse subscale played a more central
      role in anxiety and depression than did the original three subscales.
      CONCLUSIONS: It is recommended that this revised version of the CATS should be
      used in future research and clinical practice, in order that the multidimensional
      nature of abuse can be better understood.

PMID- 9631252
TI  - The effects of organizational climate and interorganizational coordination on the
      quality and outcomes of children's service systems.
AB  - OBJECTIVE: This study examines the effects of organizational characteristics,
      including organizational climate and interorganizational coordination, on the
      quality and outcomes of children's service systems. METHOD: A quasi-experimental,
      longitudinal design was used to assess the effects of increasing
      interorganizational services coordination in public children's service agencies.
      The research team collected both qualitative and quantitative data over a 3-year
      period describing the services provided to 250 children by 32 public children's
      service offices in 24 counties in Tennessee. RESULTS: Findings show that
      organizational climate (including low conflict, cooperation, role clarity, and
      personalization) is the primary predictor of positive service outcomes (the
      children's improved psychosocial functioning) and a significant predictor of
      service quality. In contrast, interorganizational coordination had a negative
      effect on service quality and no effect on outcomes. CONCLUSIONS: Efforts to
      improve public children's service systems should focus on creating positive
      organizational climates rather than on increasing interorganizational services
      coordination. This is important because many large-scale efforts to improve
      children's service systems have focused on interorganizational coordination with
      little success and none to date have focused on organizational climate.

PMID- 9631253
TI  - Emotional distress among mothers whose children have been sexually abused: the
      role of a history of child sexual abuse, social support, and coping.
AB  - OBJECTIVE: The purpose of the present study was to investigate various
      psychosocial factors related to mothers' distress following their children's
      disclosures of sexual abuse. Specifically, the relationships between mothers'
      emotional distress and a maternal history of sexual abuse in childhood, a
      maternal history of sexual abuse in adolescence, social support and coping
      strategies were examined. METHODOLOGY: One hundred and two women whose children
      disclosed sexual abuse completed a sexual abuse history questionnaire, the
      Provision of Social Relations Scale, the Coping Responses Inventory, the Brief
      Symptom Inventory, and a questionnaire requesting descriptive data. RESULTS: As
      predicted, results indicated that emotional distress was related to a maternal
      history of childhood sexual abuse, a maternal history of adolescent sexual abuse,
      a lack of support from friends and family, and greater use of avoidance coping
      strategies. As well, reliance on avoidance coping strategies was found to predict
      distress after controlling for both maternal child sexual abuse history and
      social support. CONCLUSION: The findings indicate that the distress experienced
      by mothers following a disclosure of sexual abuse is related to mothers' personal
      histories of child sexual abuse, the social support they receive, and the coping
      strategies they employ to deal with their children's disclosures. This study
      suggests that greater attention be given to psychosocial variables which can
      assist practitioners in explaining the variability in distress experienced by
      mothers and which might suggest potential interventions.

PMID- 9631254
TI  - The impact of individuals' characteristics and experiences on their definitions
      of child maltreatment.
AB  - OBJECTIVE: This study was designed to explore the extent to which individuals'
      own characteristics and experiences, particularly those involving child-rearing
      and child maltreatment, influence their definitions of abuse and neglect. METHOD:
      An anonymous written questionnaire asking respondents to rate the importance of
      individual factors to an abuse determination, as well as to rate the likelihood
      of specific acts incorporated into vignettes to constitute abuse, was
      administered to participants (n = 323) representing six groups with diverse
      relationships and experience with children: mental health professionals, legal
      professionals, medical professionals, preschool and elementary school teachers,
      parents, and adult nonparents. RESULTS: Parenting experience had only a minimal
      effect on assessments of abuse, while having encountered a case or suspected case
      of maltreatment at work predisposed individuals to view more ambiguous acts as
      less likely to constitute abuse. Nonetheless, this latter group was less
      receptive to factors offered in mitigation of perpetrator liability.
      Surprisingly, no effect was detected for individuals themselves identifying as a
      victim or perpetrator of abuse or neglect. CONCLUSIONS: Although personal
      experiences with child-rearing and child maltreatment had only a marginal effect
      on individuals' assessments of abuse and neglect, the role played by professional
      experiences with such cases should be investigated further as it does appear to
      impact these determinations. Along with the delineation of key factors discussed
      in this study, such work can assist in the development of a much needed standard
      to guide practitioners, particularly in regard to more ambiguous acts which
      tended to produce more guarded reactions from professionals.

PMID- 9631255
TI  - Sequencing and analysis of function of the promoter region of draTG genes from
      Azospirillum brasilense Yu62.
AB  - From Azospirillum brasilense Yu62, we cloned and sequenced the upstream region of
      draTG. No identified genes were found in this region except for portion of nifH,
      which is transcribed divergently from draTG. However, some potential regulatory
      elements were found, which include downstream promoter elements (DPE), upstream
      activator sequences (UAS), and A + T-rich regions. This suggests that the region
      between draT and nifH might be a regulatory region rather than an encoding
      region, and the promoter of dra operon would probably be a RpoN-dependent
      promoter. A draT::cam transcriptional fusion plasmid pAT1 was constructed in
      pAF300. The expression of draT was studied in Escherichia coli and A. brasilense
      by Cmr assay. The result showed that draT could be transcribed in A. brasilense
      but not in E. coli while grown aerobically on an LD plate. This suggests that the
      transcription of draT needs some factors which are absent in E. coli, and the
      draT upstream region has the promoter function. Using the promoter-probe vector
      pCB182, a draT::lacZ transcriptional fusion plasmid pCT1 was constructed. beta
      galactosidase activity was determined in vivo in E. coli, in the presence or
      absence of NifA of Klebsiella pneumoniae, respectively. The results demonstrated
      that NifA was not involved in the transcriptional regulation of draTG.

PMID- 9631256
TI  - Cloning and sequencing of human thrombopoietin cDNA.
AB  - Human thrombopoietin (hTPO), a ligand for the protooncogene c-mpl, is the major
      humoral regulator of megakaryocytopoiesis and platelet production affecting the
      proliferation and maturation of committed cells. Recently the hTPO gene and cDNA
      were cloned from human genome and cDNA libraries. In this report, hTPO cDNA was
      synthesized by RT-PCR from a Chinese human fetal liver. The sequence of this cDNA
      showed a high homology with hTPO cDNA in the Genebank database (accession no.
      L36052) except that base substitution occurred at four sites (497, 595, 767, and
      795 bp), which led to the change of three amino acid residues in the predicted
      protein.

PMID- 9631257
TI  - Effect on product formation in recombinant Saccharomyces cerevisiae strains
      expressing different levels of xylose metabolic genes.
AB  - The XYL1 and XYL2 genes from Pichia stipitis encoding xylose reductase (XR) and
      xylilitol dehydrogenase (XDH), respectively, were transformed into Saccharomyces
      cerevisiae. These two genes were placed in different directions under the control
      of the alcohol dehydrogenase I (ADHI) and phosphoglycerate kinase (PGK) promoters
      and inserted into the E. coli-yeast shuttle plasmid YEp24. Different recombinant
      S. cerevisiae strains were constructed with different specific activities of XR
      and XDH. The highest XR or XDH activities were obtained when the expressed gene
      was controlled by the PGK promoter and located downstream after the ADHI promoter
      gene-terminator sequence. The XR/XDH ratio (ratio of specific enzyme activities
      of XR and XDH) in these recombinant S. cerevisiae strains varied from 17.5 to
      0.06. In order to enhance xylose utilization, in the XYL1, XYL2 containing S.
      cerevisiae strains, the native TKL1 gene encoding transketolase and the TALI gene
      encoding transaldolase were also overexpressed, which showed considerably good
      growth on the xylose plate. Fermentation of the recombinant S. cerevisiae strains
      containing XYL1, XYL2, TKL1, and TAL1 were studied with mixtures of glucose and
      xylose. The strain with XR/XDH ratio of 0.06 consumed 3.25 g/L xylose and formed
      no xylitol and less glycerol and acetic acid, but more ethanol compared with the
      strains with a higher XR/XDH ratio.

PMID- 9631258
TI  - High-level expression and purification of human pro-UK cDNA in Escherichia coli.
AB  - A chemically synthesized human pro-urokinase (pro-UK) CDNA was cloned into the
      expression vector PET-11d and expressed in E. coli BL21(DE3) pLysS under the
      control of the T7 promoter. Using 0.1 mmol/L IPTG induction, the expression level
      of the recombinant pro-UK attained up to 15% of the total bacterial proteins and
      existed as inclusion bodies. After denaturation and renaturation in vitro, the
      expressed pro-UK was purified to be identified by Zn2+ selective precipitation,
      immuno-affinity chromatography, and benzamidine affinity adsorption. The specific
      activity of the purified human pro-UK was about 110,000 IU/mg.

PMID- 9631259
TI  - Fusion expression of green fluorescent protein and HCV capsid antigene in
      Escherichia coli cells.
AB  - A chimeric gene of the green fluorescent protein (GFP) and hepatitis C virus
      (HCV) core antigene were constructed and expressed in E. coli cells. The
      expressed fusion protein was examined by Dot-ELISA and Western blot and the three
      antigenic determinants were detected. The GFP-Core fusion protein showed not only
      the striking green fluorescence under natural light but also the HCV antigenic
      activity. A new method of immunological diagnosis is greatly anticipated in the
      light of this fusion protein which can be seen as the HCV antigen tagged with the
      green fluorescent protein.

PMID- 9631260
TI  - Production of rhEPO with a serum-free medium in the packed bed bioreactor.
AB  - Recombinant CHO (C2) cells producing human erythropoietin (rhEPO) were cultured
      with DMEM:F12 media containing 5% FBS for 8-10 days in a packed bed bioreactor,
      then rhEPO was produced with a serum-free medium (SFM-p) which was prepared in
      our laboratory. The SFM-p medium can support the growth of C2 cells and the
      production of rhEPO, and furthermore, it easily separates rhEPO from the culture
      supernatant. The cell culture in a packed bed bioreactor system using SFM-p was
      maintained in a stable condition for 20-25 days. The expression level of rhEPO
      was 12-28.4 mg/L. The bioreactor productivity was 71.0 mg/L.d and increased by 12
      14 fold over that of the roller bottle. The glucose consumption rate was 21
      g/L.d. At the end of 30 days of perfusion circulation, a final cell density of
      over 3.0 x 10(7)/ml of culture volume was achieved. Since the cells were
      entrapped in the polyester disk, the culture supernatant contained only a few
      detachment cells. Variations in lactate and ammonia production in the reactor
      were observed, and results showed that the productions of lactate and ammonia by
      the bioreactor were 3.5 g/L and 5 mmol/L, respectively, and did not affect the
      expression of interest protein. This experiment demonstrates that SFM-p is
      suitable for the growth and rhEPO production of recombinant C2 in the packed bed
      bioreactor.

PMID- 9631261
TI  - Study on the hydrolyzate of sugarcane bagasse to ethanol by fermentation.
AB  - Study of glucose and xylose utilization by Pichia stipitis in a limited oxygen
      supply condition revealed that the rate of glucose utilization decreased rapidly
      while that of xylose decreased slowly until the time that glucose and xylose were
      shown to level out, at which point the rate of xylose utilization increased
      rapidly. Based on the results, ethanol fermentation technology in continuous
      connective tower fermenters was advanced, e.g., fermentation by P. stipitis in an
      airlift loop tower focusing on xylose utilization and then residue glucose
      utilization by Saccharomyces cerevisiae in an overflow tower. When the fed
      hydrolyzate of bagasse was concentrated in five folds and the dilution rate was
      0.1 h-1, the total utilization ratio of reducing sugar was 97.2%; the
      concentration of ethanol was 46.4 g/L.h.

PMID- 9631262
TI  - Comparison of acid anhydrides with carboxylic acids in enantioselective enzymatic
      esterification of racemic menthol.
AB  - Optical resolution of racemic menthol has been efficiently achieved by lipase
      catalyzed enantioselective esterification in an organic solvent. The performance
      of the reaction using an acid anhydride as an acyl donor was compared with that
      using its corresponding free acid. The reactivities of acid anhydrides were found
      to be higher than their corresponding free acids, but acid anhydrides were also
      found to be easily hydrolyzed into free acids under the catalysis of the same
      enzyme. The existence of a too-high concentration of an acid anhydride in a micro
      aqueous reaction system will cause dehydration and thus deactivation of the
      enzyme, and will enhance non-selective esterification of a chiral alcohol, which
      will reduce the optical purity of the product. All these drawbacks, however,
      could be effectively overcome in a semi-batch reaction system into which
      propionic anhydride was continuously fed. This system showed some advantages over
      a batch reaction system using free propionic acid: the reaction time of dl
      menthol was shortened by half, the stability of the enzyme was much enhanced, and
      the optical purity of the product (l-menthyl ester) was kept at a similarly high
      level (> 98% ee).

PMID- 9631263
TI  - Construction of mammary gland-specific expression vectors for human clotting
      factor IX and its secretory expression in goat milk.
AB  - Two expression vectors comprised of mouse matrix attachment regions (MARs),
      bovine beta-casein gene sequence, human factor IX (hFIX) minigene, and cDNA,
      pMCIXm and pMCIX, were constructed for the purpose of a mammary gland bioreactor.
      A secretory expression system of hFIX protein in milk was made using stearylamine
      (SA) liposome to transfect plasmid DNA directly into the mammary gland lobule of
      a lactating goat. The highest production of hFIX in goat milk was 13.7 ng/ml 3
      days after transfection, and the hFIX production in the goat mammary gland
      transfected with pMCIXm containing hFIX minigene was obviously higher than that
      transfected with pMCIX containing hFIX cDNA. Activity immuno-analysis and the
      barium citrate absorption method showed that > 90% hFIX protein in milk appeared
      to be a gamma-glycosylated and biological activity. This result confirmed the
      validity of the constructed vectors for further transgenic study, and this assay
      could also find its success in the evaluation of a foreign gene expression and
      secretion in the milk as a rapid detection system using liposome to transfect DNA
      directly into the goat mammary gland.

PMID- 9631264
TI  - Revascularization procedures in the United States: are we doing too many?

PMID- 9631265
TI  - Adjunctive therapy after reperfusion therapy in acute myocardial infarction.
AB  - The current era has witnessed dramatic improvement in the treatment of acute
      myocardial infarction, due in large part to the more widespread use of
      thrombolytic therapy aimed at quickly restoring perfusion in the infarct-related
      artery. This review addresses the role of adjunctive pharmacologic therapy in the
      thrombolytic era, recognizing that much of the available clinical trial data
      supporting the role of adjunctive pharmacologic treatment strategies was
      conducted in patient populations not widely exposed to reperfusion therapy. This
      review, therefore, explores the data supporting the incremental benefit of
      therapy with beta blockers, nitrates, angiotensin-converting enzyme inhibitors,
      or magnesium in addition to thrombolytic therapy. Heparin and aspirin will not be
      discussed.

PMID- 9631266
TI  - Evaluation of hemolysis in patients with prosthetic heart valves.
AB  - The primary mechanism and most common cause of hemolytic disease in patients with
      prosthetic heart valves are mechanical trauma to red blood cells and
      paraprosthetic valvular regurgitation, respectively. Presenting features in
      patients with this condition include anemia, congestive heart failure, fatigue,
      jaundice, dark urine, and a regurgitant murmur. Various laboratory studies can be
      utilized to diagnose hemolytic anemia and to assess the severity of hemolysis.
      Transthoracic echocardiography, transesophageal echocardiography, and Doppler
      studies including color Doppler are useful imaging methods to assess valve
      function. Treatment is usually medical (oral iron); however, in patients with
      paravalvular regurgitation, surgery is often required to correct the anemia.

PMID- 9631267
TI  - Comparison of the diagnostic performance of two rapid bedside biochemical assays
      in the early detection of acute myocardial infarction.
AB  - BACKGROUND: New biochemical markers have been recently proposed as potential aids
      in the diagnosis of myocardial infarction. Assessment of these markers in real
      time by near-patient testing would allow more rapid decisions regarding critical
      therapeutic interventions. HYPOTHESIS: The diagnostic performance of two
      qualitative, whole blood assays for measurement of myoglobin/creatine kinase (CK)
      MB mass (CARDIAC STATus) and cardiac troponin T (TropT) was compared. Their
      potential in optimizing the rule-in of patients with infarction in order to
      initiate revascularization therapies was also evaluated. METHODS: A group of 101
      patients admitted to the hospital within 12 h from onset of symptoms suggestive
      of myocardial infarction was studied. A first blood sample was drawn in all
      patients immediately after admission. In patients not receiving reperfusion
      therapy (n = 61), three additional samples were also obtained 2, 4, and 6 h
      later. RESULTS: CARDIAC STATus showed good performance in patients with an
      admission time > 2 h from onset of pain (diagnostic efficiency, 71-100%).
      Conversely, TropT was not sensitive enough for acceptable efficiency. In a subset
      of 39 patients admitted within 6 h who did not meet standard enrollment criteria
      for thrombolysis, CARDIAC STATus allowed early detection of almost 50% of
      infarcts, enabling a significant implementation of alternative revascularization
      therapies. CONCLUSIONS: In patients admitted to the coronary care unit on the
      basis of case history and clinical examination, CARDIAC STATus assay is more
      effective than TropT in the early diagnosis of infarction, providing a valuable
      aid to cardiologists for confirming a suspected infarction rapidly, thus
      allowing, if indicated, recourse to revascularization therapy in clinically
      uncertain cases.

PMID- 9631268
TI  - Acute anterior wall myocardial infarction entailing ST-segment elevation in lead
      V1: electrocardiographic and angiographic correlations.
AB  - BACKGROUND: The correlation between ST elevation in lead V1 during anterior wall
      acute myocardial infarction (AMI) and the culprit lesion site in the left
      anterior descending (LAD) coronary artery is poor. HYPOTHESIS: The study was
      undertaken to assess the electrocardiographic (ECG) characteristics and
      angiographic significance of ST-segment elevation in lead V1 during anterior wall
      acute myocardial infarction (AMI). METHODS: Data from 115 patients with anterior
      wall AMI, who underwent coronary angiography within 14 days of hospitalization,
      were studied. The admission 12-lead ECG was examined and the coronary angiogram
      was evaluated for the nature of the conal branch of the right coronary artery
      (RCA) and for the culprit lesion site in the left anterior descending (LAD)
      coronary artery. RESULTS: Mean ST-segment deviation and the frequency of patients
      with ST-segment elevation > 0.1 mV were significantly lower in lead V1 than in
      lead V2 (0.136 +/- 0.111 mV vs. 0.421 +/- 0.260 mV, and 37 vs. 96%, for leads V1
      and V2, respectively). A small conal branch not reaching the interventricular
      septum (IVS) was more prevalent among patients with ST-segment elevation > 0.1 mV
      in lead V1 (67%), whereas a large conal branch was more prevalent in patients
      with ST-segment deviation (1 mV in that lead (83%, p < 0.001). No relation was
      found between ST-segment deviation in lead V1 during anterior wall AMI and the
      culprit lesion site in the LAD. CONCLUSION: ST-segment elevation in lead V1
      during first anterior wall AMI was found in one third of the patients, and its
      magnitude was lower than that in the other precordial leads. ST-segment elevation
      in lead V1 favors the presence of a small conal branch of the RCA that does not
      reach the IVS.

PMID- 9631269
TI  - Occurrence, characteristics, and outcome of patients hospitalized with a
      diagnosis of acute myocardial infarction who do not fulfill traditional criteria.
AB  - BACKGROUND: The diagnosis of acute myocardial infarction (AMI) is traditionally
      based on clinical history, elevation of serum enzyme activity, and typical
      changes in the electrocardiogram (ECG); however, not all patients who develop AMI
      fulfill these criteria on discharge from hospital. HYPOTHESIS: The aim of the
      study was to evaluate (1) the frequency with which the traditional criteria for
      AMI are not fulfilled among patients diagnosed with AMI on discharge, and (2)
      whether patients with and without these criteria differ in terms of
      characteristics, treatment, and outcome. METHODS: All patients aged < 75 years
      and hospitalized in the municipality of Goteborg with a discharge diagnosis of
      AMI were included. Fulfillment criteria for AMI were two of the following three
      points: (1) chest pain, (2) increase in cardiac enzymes, and (3) development of Q
      waves. RESULTS: In all, 1,188 admitted patients, 27% of whom were women, were
      included in the analysis. Of these, 193 (16%) did not fulfill the traditional
      criteria for AMI. These patients had an in-hospital mortality rate of 48%; of
      these, 59% died a sudden death, and of those who were autopsied (62%), 96% showed
      signs of a fresh AMI. The most common symptom on admission to hospital in
      patients who did not fulfill the traditional criteria was chest pain (34%),
      followed by dyspnea (27%) and fatigue (14%). Of those who died suddenly, fewer
      than half had been admitted to the coronary care unit. CONCLUSION: Patients
      diagnosed with AMI who do not fulfill the traditional diagnosis criteria have
      high mortality. On admission to hospital, the initial suspicion of AMI is often
      vague. Measures for earlier detection of life-threatening coronary artery disease
      among these patients are warranted.

PMID- 9631270
TI  - Plasma kinetics of chylomicron-like emulsion in renal transplant patients
      receiving cyclosporin-based immunosuppression.
AB  - BACKGROUND: Atherosclerotic cardiovascular disease is prevalent among renal
      transplant patients. Increase in serum total cholesterol, low-density
      lipoprotein, and very low-density lipoprotein is common in those patients.
      Alterations in chylomicron metabolism, however, are also related to atherogenesis
      and were not studied in renal transplant. HYPOTHESIS: The aim of this study was
      to evaluate chylomicron metabolism in renal transplant recipients receiving
      cyclosporin-based immunosuppression. We determined the plasma kinetics of
      triglyceride-rich emulsions labeled with [3H]triolein and [14C]cholesteryl oleate
      that are known to mimic the chylomicron metabolism when injected into the blood
      stream. METHODS: Fourteen renal transplant recipients with normal renal function
      (10 men, 4 women, aged 40 +/- 6.1 years) and 17 age- and gender-matched healthy
      controls received bolus injections of the chylomicron-like emulsion. Plasma
      samples were then taken at regular intervals during 60 min. Disappearance curves
      of the labels and the respective fractional clearance rates (FCR) were calculated
      in order to measure lipolysis and chylomicron remnant removal from the plasma.
      RESULTS: Fasting serum lipid levels did not differ in the two groups. The
      difference between Median FCR of [3H]triolein emulsion in renal transplant
      patients and that obtained in the controls (0.07 vs. 0.11 min-1, NS) was not
      statistically significant. Median FCR of [14C]cholesteryl oleate also did not
      differ between the groups (patients: 0.044; controls: 0.046, NS). CONCLUSION:
      These results indicate that neither chylomicron lipolysis nor remnant removal are
      affected in stable renal transplant patients treated with cyclosporin-based
      immunosuppression.

PMID- 9631271
TI  - Assessment of mitral valve volume by quantitative three-dimensional
      echocardiography in patients with rheumatic mitral valve stenosis.
AB  - BACKGROUND: Thickening of mitral leaflets in rheumatic mitral valve stenosis is
      well described in necropsy studies; however, volume computation of the thickening
      mitral leaflets has not been attempted. 4trial fibrillation is one of the
      complications of rheumatic mitral stenosis. Quantitative assessment of thickened
      mitral valve and its relation to clinical complications is clinically desirable.
      HYPOTHESIS: The study was undertaken to compare measurement of mitral valve
      volume in normal subjects and in patients with rheumatic mitral valve stenosis.
      METHODS: An HP Sonos 2500 echocardiographic system with 5 MHz multiplane
      transesophageal transducer was used for data acquisition, and TomTec Echoscan
      computer setup was used to off-line volume computation. Study subjects included
      10 normal subjects (mean age 44.8 years) and 36 patients with rheumatic mitral
      valve stenosis (22 female, 14 male) with an age range of 25 to 69 years (mean age
      47 +/- 9.6 years). Mitral valve volumes were compared between the normal subjects
      and patients with mitral valve stenosis, and further comparison was made between
      the sinus rhythm (SR) and atrial fibrillation (AF) groups in patients with mitral
      valve stenosis. In all study subjects, the mitral valve area (MVA) was determined
      by two-dimensional echocardiography. RESULTS: Quantitative three-dimensional (3
      D) echocardiography showed that mitral valve volume was significantly larger in
      patients with mitral valve stenosis than in normal subjects (9.0 +/- 2.2 and 4.5
      +/- 0.7 ml, respectively, p < 0.001). When patients with mitral valve stenosis
      were divided into the SR and AF groups, mitral valve volume was found to be
      significantly larger in the AF group than in the SR group (9.76 +/- 2.2 ml. and
      7.72 +/- 1.5 ml, respectively, p < 0.01) and patients in the AF group tended to
      be older (p < 0.05) with larger left atrial diameter (LAD) (p < 0.01). However,
      MVA between the two groups showed no statistical significance (1.1 +/- 0.43 and
      1.0 +/- 0.34 cm2, respectively, p > 0.2). When the study subjects were divided
      into two groups (< 50 and > or = 50 years) according to age, the comparison of
      mitral valve volume between these two groups (9.37 +/- 2.18 and 8.56 +/- 2.14 ml,
      p > 0.2) showed no statistical significance. CONCLUSIONS: Quantitative 3-D
      echocardiography can be applied for the measurement of mitral valve volume in
      vivo. Patients with rheumatic mitral valve stenosis with atrial fibrillation have
      a propensity to have a larger mitral valve volume and are older than the patients
      with sinus rhythm; however, the age per se does not seem to be a cause for larger
      mitral valve volume.

PMID- 9631272
TI  - Early postexercise thallium-201 reinjection after sublingual nitroglycerin
      augmentation: effects on detection of myocardial ischemia and/or viability.
AB  - BACKGROUND: Thallium-201 (201Tl) reinjection after conventional redistribution
      imaging is a standard procedure, resulting in enhanced 201Tl redistribution which
      is compatible with viable myocardium. Although this method significantly improves
      identification of viable myocardium, it increases the investigation time by
      approximately 1 h. Thus, this technique is suboptimal from the standpoint of
      patient convenience, since its routine performance may be impractical in a high
      volume nuclear medicine laboratory. HYPOTHESIS: This study was undertaken to
      evaluate the efficacy of an early 201Tl reinjection and imaging protocol in
      combination with sublingual nitroglycerin, to detect myocardial ischemia and/or
      viability, and to reduce the need for conventional (4 h) redistribution imaging.
      MATERIALS AND METHODS: In this study, 62 consecutive coronary patients, referred
      for the detection of possible myocardial ischemia and/or viability, were involved
      (mean age 55 years, range 41-70). Of those, 50 had previous angina attacks, with
      42 having a history of previous myocardial infarction; 10 patients had coronary
      artery bypass grafting; and the remaining 2 had atypical chest pain. Immediately
      after the completion of the initial postexer-cise imaging, 0.3 mg sublingual
      nitroglycerin followed by the reinjection of 1 m Ci of 201Tl were administered,
      and two further sets of images were acquired 1 h and 4 h later. RESULTS: In each
      set of images, a total of 496 segments were analyzed. On postexercise imaging,
      305 (61%) segments demonstrated defects of which 198 (65%) showed enhanced
      thallium uptake, 97 (32%) did not change, and 10 (3%) showed reverse
      redistribution on 1 h reinjection imaging (IRI). Of the 97 persistent defects,
      only 17 (6%) showed fill-in of 201Tl on 4 h redistribution imaging (CRI), while
      12 (4%) segments showed reverse redistribution. On the other hand, after
      analyzing the 62 patients of the 1 h IRI, 17 (27%) remained unchanged while in
      only 1 patient (6%) of 17 the diagnosis changed from myocardial necrosis to
      ischemia after analysis of the 4 h CRI. CONCLUSION: These results indicate that
      early postexercise reinjection of 201Tl in combination with sublingual
      nitroglycerin followed by 1 h image acquisition may prove useful for a
      comprehensive and convenient assessment of myocardial ischemia and/or viability.

PMID- 9631273
TI  - Images in cardiology. Truly total electric alternation of the heart.

PMID- 9631274
TI  - Transient cerebral ischemic attack and left atrial free-floating thrombus: a case
      report.
AB  - A patient with rheumatic mitral stenosis was found to have a free-floating
      thrombus in the left atrium during echocardiography. Subsequently, the patient
      underwent surgical treatment. At surgery, a free thrombus was found within the
      left atrium. The postoperative course of the patient was satisfactory.

PMID- 9631275
TI  - Streptococcal mural endocarditis and myocardial abscess occurring in a left
      ventricular aneurysm--case report and review.
AB  - Infection of the mural endocardium within a left ventricular aneurysm without
      valvular involvement is exceedingly rare. The presenting clinical features can be
      non-specific, and a high index of suspicion is required for its diagnosis. Delay
      in diagnosis invariably leads to a fatal outcome. Although no controlled studies
      are available to guide therapy and management of these patients, appropriate
      antibiotic therapy and early surgical resection of the infected ventricular
      aneurysm remain the cornerstone of therapy.

PMID- 9631276
TI  - Ascending aortic aneurysm and dissection in young adults with bicuspid aortic
      valve: implications for echocardiographic surveillance.
AB  - Bicuspid aortic valve (BAV) is an independent risk factor for aneurysm and
      dissection of the ascending aorta. Despite this association, routine imaging of
      the aorta has not been recommended for patients with BAV. We describe two young
      men who developed life-threatening aneurysm or dissection of the ascending aorta;
      one had a normally functioning BAV and the other was 10 years after valve
      replacement. The pathology of this condition is very similar to that found in the
      Marfan syndrome. We recommend echocardiographic surveillance of the ascending
      aorta at regular intervals, and consideration of beta-adrenergic blockade among
      patients with significant dilation.

PMID- 9631277
TI  - Alternate patterns of ventricular activation during supraventricular bigeminy.
AB  - Several investigators have previously noted that in the presence of bigeminal
      atrial extrasystoles, the premature beats may exhibit an alternate pattern of
      ventricular excitation either in the form of alternating left and right bundle
      branch block, or alternating right bundle-branch block and normal
      intraventricular conduction. However, the association of alternating
      intraventricular conduction with other types of supraventricular bigeminy has
      rarely been documented. In this report we present five diverse forms of
      supraventricular bigeminy exhibiting the phenomenon of alternating ventricular
      excitation on the early beats. Our findings suggest that the exact mechanism of
      supraventricular bigeminy is irrelevant in terms of subsequent ventricular
      events. Practically any type of supraventricular bigeminy may result in an
      alternate pattern of ventricular activation.

PMID- 9631278
TI  - Successful management of myocardial infarction during pregnancy in a renal
      transplant recipient.
AB  - Myocardial infarction (MI) complicating pregnancy in a renal transplant recipient
      is described. Management challenges of MI in pregnancy and the possible
      predisposing roles of renal transplantation and erythropoietin (EPO) use are
      discussed.

PMID- 9631279
TI  - Frank I. Marcus.

PMID- 9631280
TI  - Electrocardiographic crotchets or common errors made in the interpretation of the
      electrocardiogram.

PMID- 9631281
TI  - Is coronary heart disease mortality really falling?

PMID- 9631282
TI  - Pesticide exposures and fetal death: a review of the epidemiologic literature.
AB  - Despite considerable concern regarding the effects on reproductive outcome of
      exposures to pesticides, convincing evidence for the developmental toxicity of
      occupational and environmental pesticide exposure in humans is lacking. In this
      comprehensive review of the English language epidemiologic literature, we
      summarize studies that have examined potential associations between fetal deaths
      (both spontaneous abortions and stillbirths) and specific pesticides, as well as
      maternal and paternal employment in occupations with potential for exposure.
      While many of the epidemiologic studies to date suffer from methodologic
      problems, the data are suggestive of increased risks of fetal deaths associated
      with pesticides in general and maternal employment in the agricultural industry.
      There is a clear need for epidemiologic research that focuses on specific
      pesticide products or chemical families, with improved exposure assessment. The
      potential role of solvents in developmental toxicity associated with pesticide
      use by both males and females should also be considered.

PMID- 9631283
TI  - Physiologically based models of metal kinetics.
AB  - The issues confronting the modeler of metals kinetics are somewhat different from
      those with which the modeler of organic chemical behavior is faced. Particularly
      important features of metals kinetics include metal-protein binding and metal
      metal interactions. Reduction, and for some metals oxidation, is frequently an
      intrinsic part of metal metabolism. Alkylation/dealkylation reactions may or may
      not render the metal less active, and the behavior of alkylated or dealkylated
      metabolites must often be included in a complete kinetic model. Despite these
      complexities, the kinetics of metals are as amenable to the techniques of
      physiologically based modeling as are the kinetics of organic chemicals. Like all
      models, those for metals kinetics have the potential to organize a variety of
      observations, sometimes including apparently inconsistent observations, into a
      coherent framework of behavior, to identify needs for more complete experimental
      information, and to assist the risk assessor in making judgments concerning dose
      response relationships. Development of physiologically based models of the
      kinetic behavior of metals is in its very early stages. The kinetics of only four
      metals, arsenic, chromium, mercury, and lead, have been modeled with any degree
      of completeness. Of these, the lead model is the most fully realized at the
      present time. The chromium and mercury models are still in the process of
      development, and experimental data are being gathered to support further
      development and refinement of the arsenic model. We may expect to see continued
      progress made on these models and their practical applications, as well as the
      development of new models for other toxicologically significant metals such as
      cadmium, manganese, nickel, and aluminum.

PMID- 9631284
TI  - Macromolecular assemblages theory and simulation. Web alert.

PMID- 9631285
TI  - Structural cell biology--functional integration in macromolecular assemblages.

PMID- 9631286
TI  - Spherical viruses.
AB  - In the past two years, structural studies on spherical viruses have experienced a
      significant advance with the dramatic increase in the resolution attainable by
      cryo-electron microscopy and image reconstruction. X-ray crystallography, both
      alone and, increasingly, in combination with electron microscopy, continues to
      play a crucial role in elucidating how viruses function.

PMID- 9631287
TI  - Filamentous phage structure, infection and assembly.
AB  - The structural model of filamentous phage derived by X-ray fibre diffraction is
      supported by spectroscopic and genetic experiments. The structure of the receptor
      binding domain at the end of the phage and the structure of the phage-coded
      intracellular DNA-binding protein have been determined at high resolution. The
      recent dissection of the virus life cycle by genetic and biochemical analyses,
      combined with structural information, suggests models for virus infection and
      assembly.

PMID- 9631288
TI  - Chaperonins.
AB  - Molecular chaperones are essential to all living organisms. Their key role
      consists of mediating protein folding within the cell. Recent functional studies
      have provided more detailed information about the function and regulation of the
      chaperone network. Highlights of the past year include the crystal structure
      determinations of the asymmetric GroEL-GroES complex and of their isolated
      peptide-binding domains.

PMID- 9631290
TI  - Intermediate filament assembly: fibrillogenesis is driven by decisive dimer-dimer
      interactions.
AB  - Intermediate filaments are built from one to several members of a multigene
      family encoding fibrous proteins that share a highly conserved hierarchic
      assembly plan for the formation of multistranded filaments from distinctly
      structured extended coiled coils. Despite the rather low primary sequence
      identity, intermediate filaments form apparently similar filaments with regard to
      their spatial dimensions and physical properties. Over the past few years,
      substantial progress has been made in the elucidation of the complex expression
      patterns and clinically relevant phenotypes of intermediate filaments. The key
      question of how these filaments assemble and what the molecular architecture of
      their distinct assembly intermediates comprises, however, has still not been
      answered to the extent that has been achieved for microfilaments and
      microtubules.

PMID- 9631289
TI  - F-actin-binding proteins.
AB  - The study of proteins that bind filamentous actin (F-actin) is entering an
      exciting stage as more and more structures are determined. After more than 50
      years in which the focus was on muscle proteins, emphasis has recently shifted
      towards understanding the complex interplay among actin-binding molecules in non
      muscle cells. To date, the binding sites for eight classes of filament-binding
      molecules have been determined by combining low- to intermediate-resolution maps
      obtained by electron microscopy with atomic structures determined by X-ray
      crystallography and NMR. Recent results have dramatically accentuated the
      importance of filament geometry and actin conformation in defining these
      interactions.

PMID- 9631291
TI  - The functional significance of multimerization in ion channels.
AB  - Recently, the allosteric behavior of ion channels has been investigated by
      recording the individual steps leading to the complete activation of a cyclic
      nucleotide-gated ion channel. This information, in combination with recent
      studies on nicotinic acetylcholine receptor mutants, necessitates a modification
      of our current theories of the allosteric mechanisms of ion channels and gives
      new insights into the functional significance of multimerization in ion channels.

PMID- 9631292
TI  - The role of assembly in insulin's biosynthesis.
AB  - Insulin is synthesised as a single-chain precursor, preproinsulin, that contains
      an N-terminal signal sequence and a connecting peptide linking the A and B chains
      of the insulin molecule. Nascent proinsulin is directed into the regulated
      secretory pathway, converted to insulin and stored as microcrystals. These
      processes exploit assembly to the zinc-containing hexamer. Structural, chemical
      and genetic studies, and experiments with transgenic animals and transfected
      cells are providing new details about the molecular events in insulin's
      biosynthesis.

PMID- 9631293
TI  - GTPase-activating proteins and their complexes.
AB  - In the past year, crystallographic structures for four complexes of GTPase
      activating proteins (GAPs) with their target G proteins have been described and
      substantially enhance our understanding of how these proteins function. GAPs
      specific for the Rho and Ras families of small G proteins insert an arginine
      residue into the active site of the G protein, stabilise its switch regions and
      share an underlying topological relationship. The complex of a heterotrimeric G
      protein with its activating protein shows that the latter protein does not
      participate directly in the hydrolytic reaction and has a different structure of
      RhoGAP and RasGAP.

PMID- 9631294
TI  - The use of solid physical models for the study of macromolecular assembly.
AB  - The use of modern technology in the construction of accurate solid macromolecular
      models based on atomic coordinates and electron density functions has led us to
      re-examine the usefulness of physical models as tools for understanding molecular
      assembly and for designing detailed experimental and computational studies of the
      assembly process. Recent developments include the construction of new models,
      which have provided insights into the assembly of viruses and light harvesting
      complexes.

PMID- 9631295
TI  - Electrostatic effects in macromolecules: fundamental concepts and practical
      modeling.
AB  - The past few years have seen an exponential growth in the calculations of
      electrostatic energies of macromolecules and an increased recognition of the
      crucial role of electrostatic effects. This review considers the current state of
      the field. Focus is placed on calculations of pKas, redox potentials and binding
      energies in macromolecules and clarification of the fact that the value of the
      dielectric 'constant' of a protein depends on its definition and that small
      dielectric constants should not be used in describing charge-charge interactions
      by current continuum models.

PMID- 9631296
TI  - Protein hydration density: theory, simulations and crystallography.
AB  - Models of protein hydration are becoming increasingly more accurate in comparison
      with experimental data. The recent success of these models implies that the major
      features of the solvation layers are dominated by local correlations and that
      such correlations are universal. The excellent agreement between theoretical and
      experimental solvent electron density radial distributions marks a significant
      success in our ability to accurately model macromolecular hydration.

PMID- 9631297
TI  - Simulations of protein folding and unfolding.
AB  - The 'new view' of protein folding is based on a statistical analysis of the
      landscape for protein folding. This perspective leads to the investigation of the
      statistical distributions of protein conformations as the folding protein
      approaches the native state from unfolded states. Molecular dynamics simulations
      of both the thermodynamics of protein folding and the kinetics of unfolding are
      beginning to explore the statistical nature of these distributions. They also
      provide connections between the theory of protein folding landscapes and the
      experimental observations of the properties of key ensembles of the conformations
      populated as folding progresses.

PMID- 9631298
TI  - Simulations of the molecular dynamics of nucleic acids.
AB  - The growing amount of high quality molecular dynamics simulations generated using
      the latest methodological developments and force fields has led to a sharper
      understanding of the forces underlying the dynamics of biomolecular systems, as
      well as to stimulating insights into the structure and catalysis of nucleic
      acids. It is now clear that inclusion of long-range electrostatic interactions
      and of the aqueous and ionic environment is necessary for producing realistic and
      accurate simulations. Yet, many papers hint at a force field and protocol
      dependence of the results and thus contain the seeds for the future improvements
      that will be necessary for deepening our understanding of recognition phenomena
      and folding of nucleic acids.

PMID- 9631299
TI  - Models and simulations of ion channels and related membrane proteins.
AB  - The past year has seen major advances in our understanding of ion channels,
      resulting from molecular dynamics simulations and modelling studies. Simulations
      of gramicidin have revealed that proton conduction along a water wire is limited
      by the dynamics of water reorientation. Plausible models are now available for a
      number of other channels, including alamethicin, the influenza A virus M2
      protein, and the pore domains of the nicotinic acetylcholine receptor and Kv
      channels. Molecular dynamics simulations and continuum calculations have revealed
      some of the subtleties of the interactions between transmembrane helices and
      their lipid bilayer environment.

PMID- 9631300
TI  - Theory of biomolecular recognition.
AB  - Specific, noncovalent binding of biomolecules can only be understood by
      considering structural, thermodynamic, and kinetic issues. The theoretical
      foundations for such analyses have been clarified in the past year. Computational
      techniques for both particle-based and continuum models continue to improve and
      to yield useful insights into an ever wider range of biomolecular systems.

PMID- 9631301
TI  - Predictive docking of protein-protein and protein-DNA complexes.
AB  - Recent developments in algorithms to predict the docking of two proteins have
      considered both the initial rigid-body global search and subsequent screening and
      refinement. The result of two blind trials of protein docking are encouraging-
      for complexes that are not too large and do not undergo sizeable conformational
      change upon association, the algorithms are now able to suggest reasonably
      accurate models.

PMID- 9631302
TI  - Quantum mechanical calculations on biological systems.
AB  - Improvements in quantum chemical methods have led to increased applications to
      biological problems, including the development of potential energy functions for
      molecular mechanics and modeling of the reactive chemistry in enzyme active
      sites, with particularly interesting progress being made for metal-containing
      systems. An important direction is the development and application of hybrid
      quantum chemical-molecular mechanics methods.

PMID- 9631303
TI  - Spontaneous inflammatory bowel disease in multiple mutant mouse lines:
      association with colonization by Helicobacter hepaticus.
AB  - BACKGROUND: Both genetic and microbial factors are thought to play a role in the
      development of inflammatory bowel disease (IBD): however, no causative microbial
      agent has been clearly defined for humans or animals. Normal flora or previously
      unrecognized intestinal pathogens may contribute to the development of disease in
      susceptible hosts. A newly recognized murine Helicobacter, H. hepaticus, causes
      hepatitis in mice and in one strain of mice is linked to liver cancer. This study
      investigates the association between colonization of the lower intestinal tract
      of multiple genetically altered lines of mice with H. hepaticus, and the
      occurrence of IBD. MATERIALS AND METHODS: Rectal prolapse noted clinically in
      multiple genetically altered mouse lines was evaluated for the presence of H.
      hepaticus and histologic evidence of IBD. Fifty-five mice representing 11
      different genetic alterations were evaluated. RESULTS: H. hepaticus was detected
      in 85% of mutant mice with rectal prolapse. Histologic evidence of proliferative
      typhlitis, colitis or proctitis was present in 65% of the animals examined, 89%
      of which were positive for H. hepaticus as detected by species specific PCR.
      CONCLUSION: The presence of H. hepaticus in association with IBD in multiple
      lines of genetically altered mice suggests further studies are needed to test
      experimentally the role H. hepaticus plays in the development of IBD in
      susceptible mice. Additionally, specific mutant mouse lines infected with H.
      hepaticus in this study may provide additional models for elucidation of
      microbial and genetic factors in the pathogenesis of IBD.

PMID- 9631304
TI  - DNA sequence conservation and diversity in transposable element IS605 of
      Helicobacter pylori.
AB  - BACKGROUND: IS605, a transposable element-like sequence identified in the
      virulence-associated cag region of Helicobacter pylori reference strain
      NCTC11638, is unusual in containing two oppositely-oriented open reading frames
      whose products are homologues of the single transposases of the unrelated
      elements, IS200 and IS1341. METHODS: One hundred independent H. pylori isolates
      from different parts of the world were screened by PCR and dot blot hybridization
      to determine the presence of IS605. For some positive isolates, southern
      hybridizations and sequence analyses were done. RESULTS: Of the 100 isolates, 31
      were found to contain sequences related to each ORF with orientation and spacing
      matching those in canonical IS605-hybridizing sequences. No isolate containing
      just one ORF and not the other was found. The frequencies of IS605 carriage were
      independent of geographical origin (U.S. vs. non-U.S.), and of the probable
      virulence of the isolate (cag status, toxin production or vacA alleles, patient
      symptoms). Southern blot hybridization of six IS605-containing strains revealed
      one to nine IS605 copies per genome. Two types of DNA sequence diversity were
      found: first, a specific 100 bp deletion in two isolates; second, base
      substitution divergence of 0.4% to 7.5% in pairwise comparisons among the eight
      isolates characterized, a level of divergence similar to that seen in other H.
      pylori chromosomal genes. CONCLUSIONS: Based on these findings, we speculate that
      IS605 is a relatively ancient component of the H. pylori gene pool that has
      proliferated in this species by horizontal gene transfer, homologous
      recombination, and transposition.

PMID- 9631305
TI  - Helicobacter pylori colonization density and gastric acid output in non-ulcer
      dyspepsia and duodenal ulcer disease.
AB  - BACKGROUND: The pattern of intragastric Helicobacter pylori colonization and its
      density may be determined by parietal cell function. H. pylori bacterial products
      can inhibit gastric acid secretion from the parietal cell. The aim of this
      investigation was to study the relationship between acid output and intragastric
      H. pylori distribution and colonization density in duodenal ulcer (DU) and non
      ulcer subjects. The study included 14 patients with active DU, 10 with inactive
      DU and 10 non-ulcer dyspeptics. METHODS: Acid output studies in response to
      fasting and maximal pentagastrin stimulation, basal (BAO) and peak (PAO) acid
      outputs were calculated. A quantitative assessment of H. pylori colonization
      density in biopsies from five sites of the gastroduodenum in the active ulcer
      group, and from the antrum in inactive duodenal ulcer and non-ulcer groups.
      RESULTS: There were negative correlations between total gastroduodenal bacterial
      colonization density and, PAO (r - 0.87, p = 0.0025) and BAO (r - 0.635, p <
      0.02) in the active ulcer group. There were negative correlations between antral
      H. pylori colonization density and PAO in the active duodenal ulcer (r - 0.7449,
      p < 0.01) and non-ulcer (r - 0.5837, p < 0.1) groups but not in the inactive
      duodenal ulcer group (r - 0.1869, p > 0.2). CONCLUSIONS: An equilibrium is
      reached between gastroduodenal H. pylori colonization density and gastric acid
      secretory capacity in active duodenal ulcer disease. It is hypothesized that
      thresholds of bacterial load and acid secretory capacity, in combination, are
      required for active ulceration in DU disease.

PMID- 9631306
TI  - Helicobacter pylori and peptic ulcer disease therapies: a survey of
      gastroenterologists in Israel.
AB  - BACKGROUND: Eradication of Helicobacter pylori has become a therapeutic option in
      the treatment of patients with peptic ulcer disease. The aim of this study was to
      evaluate the current management strategies of Israeli gastroenterologists in the
      diagnosis and treatment of H. pylori-related peptic ulcer disease, 14 years after
      the discovery of H. pylori. MATERIALS AND METHODS: A questionnaire was mailed to
      all specialists in gastroenterology, members of the Israel Gastroenterological
      Association (IGA). Replies were received from 60% of Israel Board-certified
      gastroenterology specialists. RESULTS: Over 89% of the gastroenterologists
      (89.1%) noted that they recommend anti-H. pylori treatment. 94.5% said that they
      treat duodenal ulcer in the first presentation with anti-H. pylori medication and
      75% said that they do so in cases of recurrent duodenal ulcer. According to the
      replies received, there is a strong consensus towards triple treatment as the
      favored anti-H. pylori treatment; no one noted the use of dual treatment. Seven
      day triple treatment was prescribed by 83.6% of the gastroenterologists who
      responded. Of these, the great majority, 89.1%, stated that they use proton pump
      inhibitors (PPI) in combination with any two of the following antibiotics:
      metronidazole (47.3%), tinidazole (29.1%), clarithromycin (61.8%), and
      amoxicillin (40%). CONCLUSION: At the time of the survey, most Israel Board
      certified gastroenterology specialists prescribed triple anti-H. pylori treatment
      of one-week's duration.

PMID- 9631307
TI  - High concentrations of ammonia, but not volatile amines, in gastric juice of
      subjects with Helicobacter pylori infection.
AB  - BACKGROUND: Helicobacter pylori (H. pylori) produces large amounts of ammonia.
      Based on higher readings obtained with an ammonia-sensitive electrode when
      compared to a specific enzymatic assay, it has been claimed that H. pylori also
      produces potentially toxic volatile amines. METHOD: We measured ammonia
      concentrations (NH3) in gastric aspirates from 11 H. pylori positive subjects (22
      40 y, 6 M), using an ammonia electrode sensitive to ammonia and amines, and an
      enzymatic assay specific for ammonia. Continuous aspiration was performed
      overnight and 220 aspirates were analyzed before and 6 weeks after cure of H.
      pylori. Gastric samples were diluted 1:3 (before cure) and 1:1 (after cure)
      according to dilution curves constructed prior to the assays. RESULTS: Median
      (95% CI) NH3 detected by the electrode/enzymatic assay were 4.34 mM[4.12
      4.61]/4.50 mM [4.28-4.68] (p > .05) before cure and 0.54 mM[0.42-0.60]/0.73
      mM[0.71-0.81] after cure (p > .05). Intra-class correlation coefficient between
      the two methods was 0.91 before cure and 0.90 after cure (p < .001). Without
      dilution, the enzymatic assay was linear for NH3 from 0.01 to 1 mM and saturated
      at 2.5 mM; the electrode was linear for NH3 from 0.01 to 20 mM. When appropriate
      dilutions were performed, the enzymatic assay was accurate for NH3 greater than
      2.5 mM. CONCLUSION: In subjects with H. pylori infection there is a high NH3 in
      gastric juice; production of volatile amines appears to be negligible in vivo. An
      ammonia-sensitive electrode and a specific enzymatic assay are both suitable
      methods for determining NH3 in the gastric juice of subjects with H. pylori
      infection.

PMID- 9631308
TI  - Helicobacter pylori (H. pylori) in gastric mucosa of children with abdominal
      complaints: immunohistochemistry detects antigen-reactive corpus mucosa cells.
AB  - BACKGROUND: Previous morphological and serological studies of gastric
      Helicobacter pylori (H. pylori) colonization among Estonian children with
      abdominal complaints, as well as among populations of schoolchildren, have shown
      a high prevalence of H. pylori (49-60%). Based on published data concerning the
      high specificity and sensitivity of immunohistochemical detection of H. pylori,
      we examined the prevalence of H. pylori in gastric biopsy specimens of Estonian
      children by different localization and morphological type of gastritis comparing
      Giemsa staining with immunohistochemistry. MATERIAL AND METHODS: Formalin-fixed
      biopsies (107 antral, 108 corpus mucosa) of 112 children (41 boys, 71 girls, age
      range 1-16 years, median age 12 years) with abdominal complaints were stained
      with hematoxylin & eosin and Giemsa stains, as well as examined using the
      peroxidase antiperoxidase (PAP) method with polyclonal antibodies to H. pylori.
      RESULTS: Gastritis of any degree and localization was found in 84/112 (75%)
      children. Using Giemsa staining H. pylori were detected in 83/112 (74%) of all
      children, and by use of the PAP method in 55/112 (49%) (p = .001). Concordance of
      the results of immunohistochemical and Giemsa methods in antrum biopsies was 70%,
      in corpus biopsies 73%. In 12 out of 108 (11%) corpus mucosa specimens a positive
      staining with anti-H. pylori IgG was localized in the cytoplasma of corpus
      mucosal cells in the neck part of the glands. CONCLUSIONS: The prevalence of H.
      pylori was higher when employing the Giemsa stain in comparison with
      immunohistochemistry. Antibody reactivity of cells in the neck part of the corpus
      glands may either be due to cross-reactivity of anti-H. pylori IgG with
      epithelial cell epitopes, or to internalization of H. pylori by these cells,
      suggesting a pathogenic role of neck cells in an anti-H. pylori immune response.

PMID- 9631309
TI  - The ideal therapy must be defined in each geographical area: experience with a
      quadruple therapy in Spain.
AB  - BACKGROUND: Multiple therapeutic combinations have been tested to determine the
      optimal regimen(s) for Helicobacter pylori eradication, leading to very different
      results depending on the geographical area. Our goal was to evaluate the efficacy
      of a "quadruple" therapy with omeprazole, tetracycline, bismuth and metronidazole
      in our area. MATERIALS AND METHODS: We investigate 106 consecutive patients with
      active peptic ulcer disease (duodenal, gastric or both) and Helicobacter pylori
      infection. One-week therapy with omeprazole 20 mg b.i.d., tetracycline
      hydrochloride 500 mg q.i.d., colloidal bismuth subcitrate 120 mg q.i.d., and
      metronidazole 250 mg t.i.d was prescribed. Between the days 30 and 40 after
      treatment ended follow-up endoscopy was performed. Eradication was defined as
      both negative urease test and histology. Between days 90 and 360 a 13C urea
      breath test was performed in 100 patients. RESULTS: Of the 106 patients in the
      study, 91 had duodenal ulcer, 12 had gastric ulcer, and 3 had both. Side effects
      were observed in 25% of the cases. Eradication was achieved in 87.7% (93/106; CI
      79.9-93.3). Healing was obtained in 95.2% (100/105; CI 89.2-98.4); 97.8% (CI 92.4
      99.7) in those eradicated and 75% (CI 42.8-94.5) in non-eradicated (p < .01).
      CONCLUSIONS: Quadruple therapy with omeprazole, tetracycline, bismuth subcitrate
      and metronidazole achieves healing rates up to 95-100%. The 87.7% eradication
      rate obtained suggests that the regimen we used is a reasonable therapeutic
      alternative in our area.

PMID- 9631310
TI  - Optimal PPI-based triple therapy for the cure of Helicobacter pylori infection: a
      single center comparison of four 14-day schedules.
AB  - BACKGROUND: Helicobacter pylori eradication is accomplished using a wide array of
      drugs combined in a multitude of dosage schedules. The aim of the present study
      was to define the best 14-day eradication schedule using a PPI plus either two
      antibiotics or one antibiotic and bismuth. MATERIAL AND METHODS: For this study,
      367 subjects (198 males, 169 females, age 22-87 years) with document H. pylori
      infection of the stomach were recruited from out-patients of the Gastroenterology
      Department of the Venezia Hospital. In all patients, H. pylori infection was
      identified by histology and the CLO-test. Patients were treated as follows: 1)
      PPI (P) plus clarithromycin (C) 250 mg plus amoxicillin (A) 1000 mg bid (P + C +
      A); 2) P plus C plus bismuth subcitrate (B) 120 mg qid (P + C + B); 3) P plus C
      plus tinidazole (T) 500 mg bid (P + C + T); and 4) P plus A plus T bid (P + A +
      T). After two months, an upper gastrointestinal endoscopy was repeated for end
      point histological evaluation and the CLO- test. Positivity of one of the two
      methods was considered sufficient to define H. pylori as "not eradicated".
      STATISTICS: Chi-squared test and Fisher exact test. RESULTS: Thirty-three
      subjects dropped out (six due to adverse events). P + C + B was proven
      significantly less effective than P + C + A, P + C + T and P + A + T, eradication
      rates being, respectively, 75.0%, 90.5%, 87.6%, 92.0%, (p = .005, per protocol
      analysis). CONCLUSIONS: All PPI-based triple therapies tested in this study were
      effective in curing H. pylori infection; however, P + C + B resulted in rates too
      low (< 85%) to be recommended. P + C + A and P + A + T resulted in the high cure
      rates and thus may be considered the treatment of choice.

PMID- 9631311
TI  - Miconazole gel increases the cure rate of Helicobacter pylori infection when
      added to lansoprazole and amoxicillin in a randomized trial.
AB  - BACKGROUND: Miconazole is an antimycotic agent with bacteriocidal activity
      against Helicobacter pylori in vitro. Its role in the clinical eradication of H.
      pylori has not been studied. The objective of this study was to investigate the
      efficacy and side effect profile of miconazole for the treatment of H. pylori.
      MATERIALS AND METHODS: We studied 65 patients with gastritis or peptic ulcer
      disease in whom H. pylori infection was confirmed by a rapid urease test and
      microbiologic assessment. In vitro miconazole sensitivity was assessed for the H.
      pylori strains isolated from the enrolled patients. All patients were randomized
      to receive either dual therapy consisting of lansoprazole 30 mg daily and
      amoxicillin 500 mg three times a day for 14 days (LA, n = 33) or triple therapy
      using the LA regimen plus miconazole gel 100 mg three times a day for 14 days
      (LAM, n = 32). At least 8 weeks after the treatment, successful therapy was
      validated by the histological and microbiologic assessment. Adverse effects and
      drug adherence were monitored by direct questioning. RESULTS: The minimum
      inhibitory concentrations of miconazole ranged from 3.13 to 6.25 mg/L. H. pylori
      was eradicated in 16 of 33 patients (48%, 95% CI = 31% to 67%) after LA therapy,
      and 24 of 32 patients (75%, 95% CI = 59% to 91%) after LAM therapy (p < .03).
      There was no significant difference in the occurrence of adverse events between
      the two groups. CONCLUSIONS: The addition of miconazole gel to the LA regimen
      significantly improved the cure rate of H. pylori without an increase in adverse
      effects.

PMID- 9631312
TI  - An alternative non-macrolide, non-imidazole treatment regimen for curing
      Helicobacter pylori and duodenal ulcers: ranitidine bismuth citrate plus
      amoxicillin. The RBC H. pylori Study Group.
AB  - BACKGROUND: Because patients who fail to be cured of H. pylori infection
      following macrolide or imidazole therapy are difficult to treat, there is a clear
      need for a reasonably effective and simple second-line treatment regimen. The
      purpose of these two studies was to evaluate the efficacy of ranitidine bismuth
      citrate (RBC) plus amoxicillin for the cure of H. pylori infection and for
      healing duodenal ulcers and preventing ulcer relapse. MATERIALS AND METHODS: Two
      identically designed randomized, double-blind, double-dummy studies were
      conducted in patients with an H. pylori-associated duodenal ulcer. Patients were
      treated with either RBC 400 mg bid for 4 weeks plus amoxicillin 500 mg qid for 2
      weeks, RBC 400 mg bid for 4 weeks and placebo qid for 2 weeks, placebo bid for 4
      weeks and amoxicillin 500 mg qid for 2 weeks, or placebo bid for 4 weeks and
      placebo qid for 2 weeks. Patients with healed ulcers after 4 weeks of treatment
      were eligible for entry into a 24-week observation phase for the assessment of H.
      pylori status (culture, histology, and CLOtest) and ulcer relapse. RESULTS: A
      total of 229 patients with confirmed H. pylori infection at baseline were
      evaluated. Of these, 132 whose ulcers had healed entered the 24-week
      posttreatment observation phase. The combination of RBC plus amoxicillin resulted
      in higher H. pylori cure rates (55%) and higher duodenal ulcer healing (74%) than
      did either treatment alone. All treatment were well tolerated. CONCLUSIONS: The
      combination of ranitidine bismuth citrate plus amoxicillin cures H. pylori
      infection in more than half of the patients treated. This treatment regimen shows
      promise as the basis for future non-macrolide, non-imidazole triple therapy
      regimens for curing H. pylori infection. Such regimens may be appropriate second
      line treatment for patients who are resistant to or who are unable to tolerate
      macrolide- or imidazole-containing therapies.

PMID- 9631313
TI  - Effectiveness of omeprazole-amoxicillin-clarithromycin (OAC) therapy for
      Helicobacter pylori infection in a Japanese population.
AB  - BACKGROUND: Omeprazole or lansoprazole, amoxicillin, clarithromycin (PPI/AC)
      therapy has been reported to provide a high cure rate of H. pylori infection with
      few adverse effects. Effectiveness of H. pylori therapy may vary among different
      geographic regions and patient populations. However, there are few reports in
      Japan as to its effectiveness. We have, therefore, studied the effectiveness of
      H. pylori therapy in a large group of Japanese patients. METHODS: For this study,
      366 H. pylori-positive patients with peptic ulcer disease or non-ulcer dyspepsia
      (263 men and 103 women, mean age 48.5 years) were assigned to 6 groups, each
      receiving a different PPI/AC regimen. Group 1 received omeprazole (OPZ) 20 mg,
      amoxicillin (AMOX) 1500 mg, and clarithromycin (CAM) 400 mg; Group 2 OPZ 40 mg,
      AMOX 1500 mg, and CAM 400; and Group 3 OPZ 20 mg, AMOX 2000 mg, and CAM 600 mg
      daily for 14 days. The group treated with lansoprazole (LPZ) 30 mg, AMOX 1500 mg
      and CAM 400 mg was used for 14 days in Group 1L. OPZ 20 mg, AMOX 750 mg, and CAM
      200 mg were given to Group 4 for 28 days and OPZ 20 mg, AMOX 1500 mg, CAM 400 mg
      was administered to Group 5 for 7 days. Cure of infection was assessed by 13C
      urea breath test one month after completion of therapy. RESULTS: Cure rates
      calculated by excluding the patients who showed borderline value of 13C urea
      breath test (delta 13C value between 5 and 10% in Groups 1, 1L, 2, 3, 4, and 5
      were 82.7% (95% CI; 74-90), 88.9% (76-96), 84.9% (72-93), 81.3% (67-91), 84.6%
      (72-93), and 85.1% (72-94) on an intention-to-treat basis, and 88% (80-94), 95.2%
      (84-99), 95.6% (85-99), 90.7% (78-97), 95.7% (85-99) and 88.9% (76-96) on a per
      protocol basis, respectively. Adverse effects that affected compliance were
      observed in 10 of 237 patients on 14-day regiments, one of 47 on a 28-day regimen
      and one of 46 on a 7-day regimen. CONCLUSION: Two weeks PPI/AC therapy is highly
      effective for cure of H. pylori infection in the Japanese population. The low
      dose one month regimen and the one week OAC regimen were also effective in our
      patient population.

PMID- 9631314
TI  - Helicobacter pylori infection and chronic gastric acid hyposecretion.

PMID- 9631315
TI  - Helicobacter pylori and hepatitis A: a common route but uncommon mode of
      infection?

PMID- 9631316
TI  - Helper T-cell subsets, interleukins, gastritis and Helicobacter pylori.

PMID- 9631318
TI  - A perspective on the control of FES-supported standing.
AB  - This special section is about the control of electrical stimulators to restore
      standing functions to paraplegics. It addresses several important topics
      regarding the interactions of the intact central nervous systems (CNS) with the
      artificial control system. The topics are as follows: how paraplegics use their
      arms to help themselves stand up with functional electrical stimulation (FES);
      the user-driven artificial control of FES-supported standing up; a controller
      which is promising for the control of sitting down; the application of
      reinforcement machine learning for the controllers of standing up; arms-free
      standing with voluntary upper body balancing and artificially controlled ankle
      stiffness; and cognitive feedback in balancing. This Commentary introduces the
      papers in this section and relates them to earlier research.

PMID- 9631317
TI  - What does the positivity of a monoclonal antibody against H. pylori mean?

PMID- 9631319
TI  - Patient-driven control of FES-supported standing up: a simulation study.
AB  - To control movements aided by functional electrical stimulation (FES) in
      paraplegic patients, stimulation of the paralyzed lower limbs might be adjusted
      in response to voluntary upper body effort. Recently, Donaldson and Yu proposed a
      theoretical approach, called "control by handle reactions of leg muscle
      stimulation" (CHRELMS), in which stimulation of the lower limbs depends on upper
      body effort, i.e., body posture and recorded hand reactions, and is aimed to
      minimize arm forces during standing up and standing. An alternative strategy is
      presented in this paper, which accounts for voluntary upper body effort as well,
      but does not require estimation of hand reactions. The objective of this study is
      to test both strategies by applying them to a generic two-dimensional (2-D)
      neuromusculoskeletal model. The model takes into account the major properties of
      muscle and segmental dynamics during FES-supported standing-up movements of a
      paraplegic patient. In comparison to standing up without FES-support, both closed
      loop strategies yield satisfying standing-up movements although no reference
      information (e.g., a desired trajectory) is required. Arm forces can be
      significantly reduced. Using the model to optimize the controller, time-consuming
      and strenuous trial-and-error experimentation could be avoided. However, final
      experimental studies are planned to verify the presented strategies.

PMID- 9631320
TI  - Arm-free paraplegic standing--Part I: Control model synthesis and simulation.
AB  - The following paper is the first part of our investigation into the feasibility
      of arm-free paraplegic standing. A novel control strategy for unsupported
      paraplegic standing which utilizes the residual sensory and motor abilities of
      the thoracic spinal cord injured subjects is proposed. The strategy is based on
      voluntary and reflex activity of the paraplegic person's upper body and
      artificially controlled stiffness in the ankles. The knees and hips are
      maintained in an extended position by functional electrical stimulation (FES).
      The analysis of a linearized double inverted pendulum model revealed that with
      properly selected ankle stiffness the system can be easily stabilized. We
      developed a closed-loop double inverted pendulum model including a neural system
      delay, trunk muscles dynamics, body segmental dynamics and linear quadratic
      regulator (LQR) optimal controller. Through simulations of the closed-loop model
      two different strategies for disturbance rejection were explained. We
      investigated the capability of the closed-loop model to reject disturbances,
      imposed at the ankle joint (in anterior and posterior directions) for various
      stiffness levels and neural system delays in the presence of biomechanical
      constraints. By limiting permissible excursions of the center of pressure, we
      found out that the length of the foot is the most important constraint, while the
      strength of the trunk muscles is not of major importance for successful
      balancing. An ankle stiffness of approximately 10 Nm/degree suffices for arm-free
      standing of paraplegic subjects.

PMID- 9631321
TI  - Arm-free paraplegic standing--Part II: Experimental results.
AB  - In Part I, we proposed an approach for restoring unsupported standing to thoracic
      level paraplegics. The theoretical analysis and simulation of an underactuated
      double inverted pendulum, representing the standing subject, showed that arm-free
      standing might be achieved. Here in Part II, we present the mechanical apparatus
      which we used in our experiments and experimental results from tests of the
      balance-control strategy. We demonstrate that an intact and a paraplegic subject
      could perform quiet standing with the ankle stiffness set to 8 Nm/degree or even
      less (the intact subject). Both were also able to recover from disturbances,
      imposed by the artificial ankle joint of the apparatus. Introducing cognitive
      auditory feedback greatly improved the standing abilities of both subjects.

PMID- 9631322
TI  - Computer simulation of FES standing up in paraplegia: a self-adaptive fuzzy
      controller with reinforcement learning.
AB  - Using computer simulation, the theoretical feasibility of functional electrical
      stimulation (FES) assisted standing up is demonstrated using a closed-loop self
      adaptive fuzzy logic controller based on reinforcement machine learning (FLC-RL).
      The control goal was to minimize upper limb forces and the terminal velocity of
      the knee joint. The reinforcement learning (RL) technique was extended to
      multicontroller problems in continuous state and action spaces. The validated
      algorithms were used to synthesize FES controllers for the knee and hip joints in
      simulated paraplegic standing up. The FLC-RL controller was able to achieve the
      maneuver with only 22% of the upper limb force required to stand-up without FES
      and to simultaneously reduce the terminal velocity of the knee joint close to
      zero. The FLC-RL controller demonstrated, as expected, the closed loop fuzzy
      logic control and on-line self-adaptation capability of the RL was able to
      accommodate for simulated disturbances due to voluntary arm forces, FES induced
      muscle fatigue and anthropometric differences between individuals. A method of
      incorporating a priori heuristic rule based knowledge is described that could
      reduce the number of the learning trials required to establish a usable control
      strategy. We also discuss how such heuristics may also be incorporated into the
      initial FLC-RL controller to ensure safe operation from the onset.

PMID- 9631323
TI  - A strategy used by paraplegics to stand up using FES.
AB  - Many paraplegics can stand up if their leg extensor muscles are stimulated
      without feedback to the stimulator-controller. Their neurologically-intact upper
      bodies control the motion by exerting forces through the arms. To develop
      stimulator-controllers, we wish to understand the strategy they use. In two
      subjects, we measured the handle forces and the posture during standing up.
      Plotted so as to relate the handle forces to the leg joints, the results show
      that the upper body helps extend the knees and then the hips: a strategy we call
      quick knee-locking. This may keep the upper body forces within the limits of its
      strength.

PMID- 9631324
TI  - Switching curve controller for FES-assisted standing up and sitting down.
AB  - A low-level, closed-loop controller for FES-assisted standing up and sitting down
      is described. If, for able-bodied individuals, when standing up and sitting down,
      the knee angular velocity is plotted against knee angle, consistent phase-plane
      trajectories are produced. The bang-bang controller uses a model of this
      trajectory as a switching curve. The design rationale for the controller was the
      desire to avoid injuries that might occur if knee-locking on standing up and seat
      contact on sitting down are not adequately controlled. This switching curve
      controller (SCC) was incorporated within a hierarchical, finite state control
      scheme, with electrical stimulation applied bilaterally to the knee extensors.
      The SCC was tested in a pilot study on a female volunteer with paraplegia (T5/6
      ASIA A) and evaluated against an unramped, open-loop controller (OLC). The
      vertical hand forces and knee angles were measured. The subject was able to
      achieve standing up and sitting down safely using both controllers. For standing
      up, the SCC was not found to offer any quantifiable advantages over the OLC and
      was found to increase the hand force by 8.4%. In contrast, for sitting down the
      SCC was found to reduce the knee angular velocities as the subject approached the
      seat by 27%, demonstrating a safer, softer landing.

PMID- 9631325
TI  - Digital signal processing algorithms for the detection of afferent nerve activity
      recorded from cuff electrodes.
AB  - Due to the very poor signal-to-noise ratios (SNR's) usually encountered with
      whole nerve-cuff signals, the processing method typically applied, rectification
      and windowed (bin)-integration (RBI), can have serious shortcomings in extracting
      reliable information. In order to improve detection accuracy, these signals were
      further analyzed using statistical signal detection algorithms based on their
      second and higher order spectra (HOS). A comparison with both analog and digital
      RBI processing suggests that the statistical methods, due to their ability to
      separate the signal and noise subspaces, are superior. It was determined that the
      noise typically encountered with nerve-cuff electrode signals is normally
      (Gaussian) distributed. Therefore, third-order statistics can be applied to,
      ideally, completely reject the noise component. When cutaneous nerve recordings
      from the calcaneal nerve (innervating the heel area) were used in a drop-foot
      correction neural prosthesis, the detection percentage and the insensitivity to
      algorithm parameters were increased through the use of these statistical methods
      as to warrant their real-time implementation, and the inherent additional
      processing hardware that entails.

PMID- 9631326
TI  - Stretch reflex sensitivity: effects of postural and muscle length changes.
AB  - In this study, a combination of clinical evaluation, laboratory testing, and
      model simulation of spasticity is performed under various postural conditions to
      investigate the changes in the sensitivity and specific mechanisms of spasticity.
      Fifty-nine multiple sclerosis patients participated in the study and received
      spasticity evaluation based on both the Ashworth scale and the pendulum test.
      Spasticity was found to increase in the pendulum test when the subjects were
      tested in a supine posture, compared to when they were sitting. Three patterns of
      stretch reflex response were seen for similar leg swing trajectories. While it
      was clear that the increased stretch of rectus femoris in the supine posture
      contributed to the increased spasticity, the results of modeling showed that
      other more complex factors were also involved. The supraspinal descending
      modulation associated with postural control may play a more dominant role in the
      severity of spasticity. The results suggest that the biomechanical test of
      spasticity should be performed for several different postures or ranges of
      movement with muscle activities monitored simultaneously, so that the effect of
      various factors can be examined. The work also indicates that a
      neuromusculoskeletal model with detailed muscle dynamics and stretch reflex loops
      is a valuable tool for investigating the neural mechanisms of spasticity.

PMID- 9631327
TI  - Functional neuromuscular stimulation for combined control of elbow extension and
      hand grasp in C5 and C6 quadriplegics.
AB  - Spinal cord injury sustained at the C5/C6 level leaves an individual without
      voluntary control of the muscles of the forearm, hand, or of the elbow extensors.
      The objective of this research project was to integrate functional neuromuscular
      stimulation (FNS) control of elbow extension with a previously developed system
      that provides hand grasp in order to increase the working volume in space in
      which users can perform functional tasks. Elbow extension control was achieved by
      detecting the position of the arm in space and determining the magnitude of the
      gravitational moment acting to oppose extension. An accelerometer was used as the
      command control source, and this sensor was placed over the ulna near the elbow
      joint to detect static (gravitational) acceleration, and therefore the
      gravitational moment acting about the elbow joint. This value determined the
      level of electrical stimulation required to activate the triceps muscles to full
      extension against these forces. Combined FNS control of elbow extension and hand
      grasp was implemented in two quadriplegic subjects. Both subjects were able to
      reach and grasp objects at locations in space which were unattainable without
      triceps activation.

PMID- 9631328
TI  - Analysis of current density and related parameters in spinal cord stimulation.
AB  - A volume conductor model of the spinal cord and surrounding anatomical structures
      is used to calculate current (and current density) charge per pulse, and maximum
      charge density per pulse at the contact surface of the electrode in the dorsal
      epidural space, in the dorsal columns of the spinal cord and in the dorsal roots.
      The effects of various contact configurations (mono-, bi-, and tripole), contact
      area and spacing, pulsewidth and distance between contacts and spinal cord on
      these electrical parameters were investigated under conditions similar to those
      in clinical spinal cord stimulation. At the threshold stimulus of a large dorsal
      column fiber, current density and charge density per pulse at the contact surface
      were found to be highest (1.9.10(5) microA/cm2 and 39.1 microC/cm2.p,
      respectively) when the contact surface was only 0.7 mm2. When stimulating with a
      pulse of 500 microseconds, highest charge per pulse (0.92 microC/p), and the
      largest charge density per pulse in the dorsal columns (1.59 microC/cm2. p)
      occurred. It is concluded that of all stimulation parameters that can be selected
      freely, only pulsewidth affects the charge and charge density per pulse in the
      nervous tissue, whereas both pulsewidth and contact area strongly affect these
      parameters in the nonnervous tissue neighboring the electrode contacts.

PMID- 9631329
TI  - A comparison between control methods for implanted FES hand-grasp systems.
AB  - Implanted neuroprostheses employing functional electrical stimulation (FES)
      provide grasp and release to individuals with tetraplegia. This paper describes
      and compares three methods of controlling the stimulated hand movement: shoulder
      position, wrist position and myoelectric activity from the wrist extensors. Three
      experienced neuroprosthesis users were evaluated with each of the control methods
      by performing a grasp release test (GRT). A significant improvement was found
      between each functional electrical stimulation (FES) method and tenodesis without
      FES. No significant difference in overall performance was found between the three
      FES methods of control. Each method of control demonstrated advantages and
      disadvantages which depend upon characteristics of the individual patient.
      Factors which must be considered are injury level, voluntary wrist strength,
      proximal upper limb strength, the level of cognition of the patient, hand-grasp
      characteristics, cosmeses, importance of using both arms, and personal
      preference. Due to the unique characteristics of each controller type, it is
      advantageous to have each type available for the FES patients to adapt the system
      to the needs and desires of the individual patient.

PMID- 9631330
TI  - Segment velocities in normal and transtibial amputees: prosthetic design
      implications.
AB  - Dynamic elastic response foot and ankle prostheses (Seattle-Lite, Flex Foot,
      etc.) used by transtibial amputees feature substantial design improvements over
      conventional designs (SACH, Single Axis, etc.). Despite this progress,
      transtibial amputees continue to expend greater energy than normals. Increased
      residual limb EMG data and altered gait patterns suggest that impaired mobility
      may be the cause of overactive muscles in early stance. Prosthetic mobility was
      therefore quantified by measuring foot, shank and thigh velocities in nine
      transtibial amputees, wearing three different foot designs: Single Axis (SA),
      Seattle Lite (SL) and Flex Foot (FF). The magnitude, timing and rate of segment
      velocities for each prosthetic design, characterizing early stance mobility, were
      compared with corresponding measures in normal, nonamputee (NA) controls using
      Dunnett's test. Regardless of foot type, transtibial (TT) amputees walked slower
      than non amputee controls (63.3-65.8 m/min versus 78.5 m/min, p < 0.05) and their
      stride length was shorter (1.21-1.26 m versus 1.41 m, p < 0.01). In early stance,
      peak foot and shank velocities were lower (p < 0.01) for both the SL and FF while
      only shank velocity was lower (p < 0.01) with the SA compared to NA controls.
      Significant delays in the timing of early stance events such as peak shank
      velocity, peak ankle plantarflexion and peak knee flexion compromised shank and
      knee stability in TT amputees. Foot and shank mobility was uncontrolled with the
      SA design while ankle mobility was restricted by the FF and SL feet. In NA
      controls on the other hand, appropriate timing and rate of segment velocity
      changes preserved dynamic stability and forward progression in early stance. This
      was evidenced by rapid decreases in foot and shank velocity as the thigh velocity
      increased during weight acceptance. Future prosthetic designs should provide TT
      amputees with improved ankle mobility that attempt to capture the dynamic
      characteristics of a normal articulation between the foot and shank segments
      during the early stance weight acceptance period.

PMID- 9631331
TI  - Integrated analyzer and classifier of glottographic signals.
AB  - Electroglottography (EGG) and photoglottography (PGG) are two plausible methods
      to study voice production for monitoring the patterns of laryngeal vibrations. It
      has been suggested that measures such as open quotient and speed quotient
      calculated from glottographic signals can provide useful information regarding
      pathological phonation. In this paper, an integrated analyzer and classifier of
      glottographic signals was implemented. The system makes it possible to calculate
      the measures from digitized EGG and PGG signals automatically in order to examine
      vocal fold abnormality. The system developed several techniques to extract
      features from glottographic signals and proposed a statistical classification
      method that can possibly aid the diagnosis process. To check the reliability of
      the system, a training set and a test set of glottographic signals from normal
      people and patients with recurrent/superior laryngeal paralysis were analyzed and
      classified by the system. The results showed that the system is a useful tool for
      quantitative study of phonatory pathophysiology and can be used by the examiner
      who is interested in the clinical examination of glottographic signals. Moreover,
      glottographic techniques may have some clinical applications in the quantitative
      documentation of phonatory function in patients with voice disorders but requires
      further evaluation before clinical application.

PMID- 9631332
TI  - Hearing aid electromagnetic interference from digital wireless telephones.
AB  - Several in-the-ear (ITE) and behind-the-ear (BTE) hearing aids were tested for
      audible interference at various distances from five types of digital wireless
      telephones. The interference which takes the form of a buzzing and a static sound
      was quantified using a calibrated system including a frequency analyzer and a
      pressure field microphone. The output of the each hearing aid was coupled to the
      microphone via Tygon tubing and a standard 2 cc coupler. The highest interference
      induced sound pressure level (SPL), 122.5 dB, was measured from a BTE hearing aid
      placed within 2 cm of a transmitting Global System for Mobile Communications
      (GSM) phone. In this case, interference was detected up to a separation distance
      of almost 3 m. While all phones tested produced a similar interference level
      within 2 cm of this hearing aid, interference SPL from the code division multiple
      access (CDMA)-based system decreased more rapidly with distance than the time
      division multiple access (TDMA)-based phones tested.

PMID- 9631333
TI  - Effect of intestinal Lactobacillus starter cultures on the behaviour of
      Staphylococcus aureus in fermented sausage.
AB  - The effects of Lactobacillus strains isolated from intestinal tracts for starter
      cultures of fermented sausage on the growth rate and enterotoxin production of
      Staphylococcus aureus were studied at two fermentation temperatures of 20 degrees
      C and 35 degrees C. Initial inoculated populations in the sausage batter were
      approx. 10(4) cfu/g for S. aureus and 10(7) cfu/g for the Lactobacillus strain as
      a starter culture. Samples of sausage were taken during fermentation and analyzed
      for pH and microbial populations. In control lots without inoculation of
      Lactobacillus strains, staphylococcal enterotoxin was detected during
      fermentation at each temperature. Of three intestinal Lactobacillus strains, L.
      rhamnosus FERM P-15120 and L. paracasei subsp. paracasei FERM P-15121 inhibited
      the growth and enterotoxin production of S. aureus in sausages during
      fermentation at both temperatures, although L. acidophilus FERM P-15119 could not
      satisfactorily suppress them. The effect of the two selected strains in meat
      fermentation (i.e., fermentation time, acid production, inhibition of S. aureus)
      was the same as that of a commercial L. sake starter culture for fermented
      sausage. These results suggest the intestinal Lactobacillus strains selected in
      this study could be utilized as a starter culture to produce new fermented meat
      products that are microbiologically safe.

PMID- 9631334
TI  - Revised model for aerobic growth of Shigella flexneri to extend the validity of
      predictions at temperatures between 10 and 19 degrees C.
AB  - Although Shigella is a major foodborne pathogen, its growth in foods has received
      little attention. Growth of S. flexneri 5348 inoculated into commercially
      available sterile foods (canned broths, meat, fish, UHT milk, baby foods) was
      studied at 10 to 37 degrees C. S. flexneri was enumerated by surface-plating on
      Tryptic Soy Agar and growth curves were fitted by means of the Gompertz equation.
      Observed growth kinetics values and values calculated using a previously
      developed response surface model compared favorably for growth at 19 to 37
      degrees C, but not at < 19 degrees C. To refine the model, additional data were
      collected for growth at 10 to 19 degrees C. A total of 844 tests in BHI broth,
      representing 197 variable combinations of temperature (10-37 degrees C), pH (5.0
      7.5), NaCl (0.5-5.0%) and NaNO2 (0-1000 ppm) was used for the revised model. The
      revised model, developed in BHI, gave significantly better agreement of
      calculated growth kinetics values with those observed in foods at 10 to 19
      degrees C.

PMID- 9631335
TI  - Quantitative risk assessment for Escherichia coli O157:H7 in ground beef
      hamburgers.
AB  - Quantitative Risk Assessment (QRA) is a methodology used to organize and analyze
      scientific information to estimate the probability and severity of an adverse
      event. Applied to microbial food safety, the methodology can also help to
      identify those stages in the manufacture, distribution, handling, and consumption
      of foods that contribute to an increased risk of foodborne illness, and help
      focus resources and efforts to most effectively reduce the risk of foodborne
      pathogens. The term Process Risk Model (PRM) is introduced in this paper to
      describe the integration and application of QRA methodology with scenario
      analysis and predictive microbiology to provide an objective assessment of the
      hygienic characteristics of a manufacturing process. The methodology was applied
      to model the human health risk associated with Escherichia coli O157:H7 in ground
      beef hamburgers. The PRM incorporated two mathematical submodels; the first was
      intended to described the behaviour of the pathogen from the production of the
      food through processing, handling, and consumption to predict human exposure. The
      exposure estimate was then used as input to a dose-response model to estimate the
      health risk associated with consuming food from the process. Monte Carlo
      simulation was used to assess the effect of the uncertainty and variability in
      the model parameters on the predicted human health risk. The model predicted a
      probability of Hemolytic Uremic Syndrome of 3.7 x 10(-6) and a probability of
      mortality of 1.9 x 10(-7) per meal for the very young. These estimates are likely
      high for all hamburger meals, but may be reasonable for the home-prepared
      hamburgers described by this model. The efficacy of three risk mitigation
      strategies were evaluated by modifying the values of the predictive factors and
      comparing the new predicted risk. The average probability of illness was
      predicted to be reduced by 80% under a hypothetical mitigation strategy directed
      at reducing microbial growth during retail storage through a reduction in storage
      temperature. This strategy was predicted to be more effective than a hypothetical
      intervention which estimated a plausible reduction in the concentration of E.
      coli O157:H7 in the feces of cattle shedding the pathogen and one aimed at
      convincing consumers to cook hamburgers more thoroughly. The conclusions of this
      approach are only accurate to the extent that the model accurately represents the
      process. Currently, uncertainty and ignorance about the hygienic effects of the
      individual operations during production, processing, and handling limit the
      applicability of a PRM to specify HACCP criteria in a quantitative manner.
      However, with continuous improvement through stimulated research, a PRM should
      encompass all available information about the process, food, and pathogen and
      should be the most appropriate decision-support tool since it represents current
      knowledge.

PMID- 9631336
TI  - Adhesion of some probiotic and dairy Lactobacillus strains to Caco-2 cell
      cultures.
AB  - The adhesion of 12 different Lactobacillus strains was studied using Caco-2 cell
      line as an in vitro model for intestinal epithelium. Some of the strains tested
      have been used as probiotics, and most of them are used in the dairy and food
      industry. Human and bovine enterotoxigenic Escherichia coli strains were used as
      positive and negative control, respectively. Bacterial adhesion to Caco-2 cell
      cultures was quantitated using radiolabelled bacteria. The adherence of bacteria
      was also observed microscopically after Gram staining. Viability of bacteria
      prior to adhesion was verified using flow cytometry. Among the tested strains, L.
      casei (Fyos) was the most adhesive strain and L. casei var. rhamnosus
      (Lactophilus) was the least adhesive strain, approximately 14 and 3% of the added
      bacteria adhered to Caco-2 cell cultures, respectively. The corresponding values
      for positive and negative control E. coli strains were 14 and 4%, respectively.
      The Lactobacillus strains tested could not be divided into distinctly adhesive or
      non-adhesive strains, since there was a continuation of adhesion rates. The four
      most adhesive strains were L. casei (Fyos), L. acidophilus 1 (LC1), L. rhamnosus
      LC-705 and Lactobacillus GG (ATCC 53103). No significant differences in the
      percentage adhesion were observed between these strains. Adhesion of all the
      strains was dependent on the number of bacteria used, since an approximately
      constant number of Caco-2 cells was used, indicating that the Caco-2 cell binding
      sites were not saturated. Viability of bacteria was high since approximately 90%
      of the bacteria were viable with the exception of L. acidophilus 1 which was 74%
      viable. Microscopic evaluations agreed with the radiolabelled binding as
      evidenced by observing more bacteria in Gram-stained preparations of good
      adhering strains compared to poorly adhering strains.

PMID- 9631337
TI  - Evaluation of a new arcobacter enrichment medium and comparison with two media
      developed for enrichment of Campylobacter spp.
AB  - The productivity of an arcobacter enrichment medium (AM), newly developed by
      Oxoid was compared with two campylobacter enrichment media (Preston broth (Oxoid)
      and LabM broth), with arcobacter basal medium (ABM) as control. Twenty strains of
      Arcobacter and Campylobacter spp. were tested for growth, with target inocula of
      < 4 cfu per ml of medium. Incubation was carried out aerobically for 48 h with
      tightly closed caps at 25 degrees C for arcobacters and 37 degrees C for
      campylobacters. After incubation the numbers of cfu in the broths were counted by
      surface-plating on blood agar. None of the Campylobacter spp. grew in the
      complete AM, and only one grew (very poorly) in the arcobacter basal medium.
      However, AM supported good growth of all three species of Arcobacter (A.
      butzleri, A. skirrowii and A. cryaerophilus) which have been associated with
      human and animal disease. The one strain of A. nitrofigilis tested failed to grow
      in any of the media except poorly in ABM. None of the Arcobacter spp. grew in
      Preston Broth, but nine grew in LabM broth, although productivity was poor
      compared to AM. None of the Campylobacter spp. grew in AM and only one grew (very
      poorly) in ABM.

PMID- 9631338
TI  - Predictive models as means to quantify the interactions of spoilage organisms.
AB  - The purpose of this paper is to quantify the interactions of some groups of
      spoilage organisms that can be usually found in refrigerated meat stored in air,
      such as: Enterobacteriaceae, Pseudomonas, Acinetobacter, Psychrobacter,
      Shewanella, Carnobacterium, Lactobacillus, Leuconostoc, Brochothrix and Kurthia
      spp. The growth of these organisms was studied in the range of temperature 2-11
      degrees C and pH 5.2-6.4, which is characteristic of refrigerated meat. The main
      growth parameters (maximum specific growth rate and lag time) were modelled by
      multivariate quadratic polynomials of temperature and pH. The interactions of the
      organisms were analyzed by comparing their growth models obtained in isolation
      with those obtained in mixture. The difference between the models was quantified
      by statistical F-values which were used to measure how much the growth of an
      organism or group of organisms was affected by others and which of them dominated
      their joint growth.

PMID- 9631339
TI  - Production of fermented milk using a malty compound-producing strain of
      Lactococcus lactis subsp. lactis biovar. diacetylactis, isolated from Zimbabwean
      naturally fermented milk.
AB  - Malty compound-producing Lactococcus lactis subsp. lactis biovar. diacetylactis
      strain INF-DM1, originally isolated from naturally fermented milk in Zimbabwe was
      used to prepare fermented milk from ordinary milk, milk enriched with 2.5% (w/v)
      skimmed milk powder and by 2.5% (w/v) increase in dry matter by ultrafiltration.
      Inoculated milk was incubated at 22, 30 and 37 degrees C. Analyses were made
      after 0, 9, 18 and 24 h incubation and also after 24 h incubation followed by
      storage for one week at 4 degrees C. Samples were analysed for volatile compounds
      including malty compounds and for organic acids, pH and log cfu/g. All samples
      were also judged for sensory attributes. Products made from enriched milks showed
      increased viscosity which was most marked in ultrafiltrated milk incubated at 30
      and 37 degrees C. The levels of certain compounds (lactic acid, citrate and
      diacetyl) were significantly affected by milk type. Incubation temperature had a
      significant effect on starter growth rate and the rate of production and amount
      of the malty compounds, lactate, diacetyl, ethanol, acetoin and acetaldehyde. 3
      Methyl butanal concentrations were above the taste threshold level of 0.06 ppm in
      almost all products, including stored products. Although initial growth rate was
      fastest at 37 degrees C, an uncoupling of acid production and growth was observed
      after 9 h incubation, suggesting that this is above the optimum temperature for
      this strain. In addition, products incubated at 37 degrees C showed a tendency to
      whey separation, indicating that this temperature is also too high to give
      optimum product quality. All products attained good scores in sensory analysis
      provided that fermentation was complete. Variation in the levels of malty
      compounds during the fermentation had no significant effect on the sensory score
      for total flavour.

PMID- 9631340
TI  - Is IPT time-limited psychodynamic psychotherapy?
AB  - Interpersonal psychotherapy (IPT) has sometimes but not always been considered a
      psychodynamic psychotherapy. The authors discuss similarities and differences
      between IPT and short-term psychodynamic psychotherapy (STPP), comparing eight
      aspects: 1) time limit, 2) medical model, 3) dual goals of solving interpersonal
      problems and syndromal remission, 4) interpersonal focus on the patient solving
      current life problems, 5) specific techniques, 6) termination, 7) therapeutic
      stance, and 8) empirical support. The authors then apply both approaches to a
      case example of depression. They conclude that despite overlaps and similarities,
      IPT is distinct from STPP.

PMID- 9631341
TI  - The Children's Play Therapy Instrument (CPTI). Description, development, and
      reliability studies.
AB  - The Children's Play Therapy Instrument (CPTI), its development, and reliability
      studies are described. The CPTI is a new instrument to examine a child's play
      activity in individual psychotherapy. Three independent raters used the CPTI to
      rate eight videotaped play therapy vignettes. Results were compared with the
      authors' consensual scores from a preliminary study. Generally good to excellent
      levels of interrater reliability were obtained for the independent raters on
      intraclass correlation coefficients for ordinal categories of the CPTI. Likewise,
      kappa levels were acceptable to excellent for nominal categories of the scale.
      The CPTI holds promise to become a reliable measure of play activity in child
      psychotherapy. Further research is needed to assess discriminant validity of the
      CPTI for use as a diagnostic tool and as a measure of process and outcome.

PMID- 9631342
TI  - Affect and therapeutic process in groups for chronically mentally ill persons.
AB  - A dynamic group treatment model for chronically ill persons allowing them to
      determine the frequency of attendance empowers the members and potentiates group
      development. This format respects patients' needs for space as represented by
      missed meetings. In this context, absences are formulated as self-protective and
      self-stabilizing acts rather than as resistance. In an accepting, supportive
      environment, members can be helped to explore affects and gain insight into their
      behaviors. A clinical example illustrates patients' examination of the meaning of
      missing and attending sessions, with particular focus on intensity of
      involvement, autonomy, and control. In the process of testing the therapist and
      group, members show capacity to gain insight into recent in-group and extra-group
      behaviors.

PMID- 9631343
TI  - Teaching psychiatric trainees to respond to sexual and loving feelings. The
      supervisory challenge.
AB  - The intimate nature of the psychodynamic psychotherapy process requires that
      trainees be educated to deal competently with sexual and loving feelings that
      arise during psychotherapy. The absence of substantive teaching on these complex
      treatment issues places a responsibility on the psychotherapy supervisor to
      educate trainees about the erotic aspects of transference/countertransference. A
      model of supervision addressing sexual feelings in treatment relationships is
      proposed and discussed with reference to clinical vignettes.

PMID- 9631344
TI  - A helpful way to conceptualize and understand reenactments.
AB  - Attempts to understand the purpose and the etiology of reenactments can lead to
      confusion because reenactments can occur for a variety of reasons. At times,
      individuals actively reenact past traumas as a way to master them. However, in
      other cases, reenactments occur inadvertently and result from the psychological
      vulnerabilities and defensive strategies characteristic of trauma survivors. This
      article offers a means to conceptualize and understand the many ways in which
      reenactments can occur. Psychotherapeutic strategies are offered to help
      individuals integrate past traumas and decrease their chances of becoming
      involved in destructive reenactments.

PMID- 9631345
TI  - Expectancy, the therapeutic alliance, and treatment outcome in short-term
      individual psychotherapy.
AB  - Patient and therapist expectancies regarding the "typical session" were measured
      during a controlled trial of short-term, time-limited individual psychotherapy.
      Relationships between expectancy ratings and measures of the therapeutic alliance
      and treatment outcome were examined. Significant relationships were tested in the
      presence of a competing predictor variable, either pre-therapy disturbance
      (depression) or the patient's quality of object relations (QOR). Expectancies
      were associated strongly with the alliance but only moderately with treatment
      outcome. In most instances, expectancy and QOR combined in an additive fashion to
      account for variation in alliance or outcome. The patient's capacity for mature
      relationships and expectancies for therapy appear to be important determinants of
      treatment process and outcome. The clinical value of establishing accurate,
      moderate expectancies prior to therapy is considered.

PMID- 9631346
TI  - Satisfaction of Manhattan psychiatrists with private practice. Assessing the
      impact of managed care.

PMID- 9631347
TI  - Reducing thrombolytic therapy time delays in the emergency department.
AB  - A 1 year (1995) retrospective audit of all patients who were discharged or died,
      with a primary diagnosis of acute myocardial infarction (AMI) was conducted at
      Auburn Hospital, a level 4 district hospital in Sydney's western suburbs. After
      their first echocardiogram (ECG), 21 patients of 129 patients who had a primary
      diagnosis of AMI in the Emergency Department at this time were given thrombolytic
      therapy. For eight patients there was a time delay of over 60 min to commencement
      of thrombolytic therapy. This time delay exceeded the Australian Council of
      Health-care Standards guidelines and was targeted as a quality improvement
      activity. The hospital cardiologist convened meetings of medical and nursing
      staff, to develop an action plan for reducing these delays. The strategies
      adopted, implemented between April and September 1996, involved (i) keeping the
      ECG machine in the emergency department at all times, (ii) installing a facsimile
      machine, (iii) keeping Alteplase (rt-PA) in the emergency department, (iv) staff
      education, (v) allowing senior medical staff to initiate treatment if the
      consultant was not readily contactable. Resulting from these initiatives time
      delays (after first ECG) were reduced from a median time of 55 min in 1995 to a
      median time delay of 43 min in 1997. This study highlights areas of unnecessary
      delay in patients receiving thrombolytic therapy and shows that these delays can
      be reduced by the implementation of relatively simple strategies by medical and
      nursing staff. Time delays from the development of symptoms (usually chest pain)
      to arrival at triage were recorded when such a time was specified in the clinical
      notes. The median delay from the development of chest pain to triage was 73 min.

PMID- 9631348
TI  - Attitudes of mental health personnel towards rating outcome.
AB  - Outcome measurement is becoming an integral part of health-care delivery. The
      attitudes of staff towards this development are important as they may influence
      ratings themselves, improve the design of measures and indicate how outcome
      assessment should be introduced into services. In this preliminary study, we
      surveyed staff from Central Sydney Mental Health Services who had taken part in a
      Commonwealth-funded project which had required them to rate patient outcome. The
      major concern expressed by respondents was that rating outcome was too time
      consuming. More than half were not in favor of measuring outcome routinely even
      if it meant providing a better service to patients. The study methodology had
      limitations. However, if our findings are corroborated, attention will need to be
      paid to staff attitudes to outcome assessment so that ratings are more reliable
      and valid, properly inform treatment and meaningfully influence resource
      allocation.

PMID- 9631349
TI  - Determining the function of a hospital clinical ethics committee: making ethics
      work.
AB  - The objective of this study was to identify ethical issues of greatest concern to
      hospital staff, and to establish perceptions regarding the optimal function of a
      Clinical Ethics Committee (CEC). The design involved a descriptive, cross
      sectional study using a self-report questionnaire, which was sent to a random
      sample of medical, nursing, allied health, technical and administrative staff
      working at the John Hunter Hospital (a 650-bed, urban, teaching hospital in New
      South Wales) in September 1995. The questionnaires were sent to 565 staff and
      completed by 287: an overall compliance rate of 51%. Although the majority of
      staff supported the existence of the CEC in principle, approximately two-thirds
      were actually aware of its existence and less than 10% were aware of
      policies/guidelines produced by the CEC. Ethical issues of greatest concern to
      respondents were informed consent and confidentiality. Most believed that the
      main function of the CEC should be education and policy development; fewer
      supported a role in case consultation or case review, and even less believed that
      the CEC should take any role in resource allocation decisions. While there is a
      strong degree of support for the existence of a CEC, there is considerable
      variation in opinion regarding what should be its function and how it should be
      organized. The results of this study provide some insight into the issues
      associated with the emergence of CECs in an Australian context.

PMID- 9631351
TI  - Primary total knee replacement: short-term outcomes in an Australian population.
AB  - This study evaluated the short-term outcome of primary total knee replacement,
      using standard and reliable outcome measures, for osteoarthritis in an Australian
      population. This study also compared the pre-operative health status of the
      patient population with population norms using a quality of life questionnaire.
      Using the medical outcome study (MOS) 36-item short form health survey (SF-36),
      there was a statistically significant improvement in physical functioning and
      bodily pain in males and bodily pain, vitality, role-emotional and mental health
      in females (P < 0.05). A statistically significant improvement was also seen in
      Knee Society Scores following surgery for both males and females (P < 0.05).
      Comparison of pre-operative SF-36 data to age-matched Australian normative values
      demonstrate that female patients requiring total knee replacement were
      significantly below the norms in virtually all health dimensions while males were
      significantly below the norms in mainly physical health dimensions (P < 0.01).

PMID- 9631350
TI  - Severe exacerbation of chronic obstructive airways disease: health resource use
      in general practice and hospital.
AB  - The objective of this study is to examine the treatment of exacerbations of
      chronic obstructive airways disease (COAD) in the hospital and in the community
      setting using a retrospective study of patients admitted to a major teaching
      hospital combined with a general practice chart audit. The admission records for
      248 admissions from 128 patients were reviewed. Most patients (70%) had visited
      their GP within 2 weeks of admission, antibiotics were prescribed for 30% of the
      exacerbations while 51% were treated with ingested corticosteroids. During
      hospitalization, features of infection were present in 64% (n = 159) of
      exacerbations and 79% (n = 196) received antibiotics. Patients were also treated
      with nebulized bronchodilators, oxygen and corticosteroids (82%). The median
      length of stay was 10 days (range 0-55). There was a high readmission rate (70%)
      at 1 year for exacerbation of COAD during the study period. Exacerbations of COAD
      frequently demonstrated the clinical features of infection. Treatment in general
      practice was less intensive than in hospital, and there is a need to reconcile
      these differences with studies of early therapy with antibiotics and
      corticosteroids. Although corticosteroids were used less often in general
      practice, the literature in this area is not conclusive and the evidence
      supporting guideline recommendations is not explicit. There are opportunities to
      examine the role of early therapy and early discharge programmes to minimize the
      cost burden from exacerbations of COAD.

PMID- 9631352
TI  - Implementation of quality improvement methodology and the medical profession.
AB  - Modern quality management (QM) has evolved in industry over the last few decades
      to be a major factor in organizational structure and focus. The health industry
      has to a degree recognized or perceived merits in this model and has applied the
      principles of QM to many of its activities. It has also incorporated the concept
      of a commitment to quality improvement (QI) into its most recognized peer-review
      structure, hospital accreditation (ACHS). Apparent resistance exists in the
      medical fraternity to a transition from audit-focused quality assurance to
      contemporary systematic QI. An understanding of this issue may be gained from
      analysis of the medical profession's perception of QI, factors in the historical
      structures within health, and a review of the factors which hinder the transition
      to QI. By considering within a framework of organisational behaviour theory
      (OBT), some key concepts it is possible to work towards some solutions and
      proposals. These concepts include attitude, motivation, conflict, organizational
      change and development. It is likely that the appropriate focus should be broader
      than the 'recalcitrant group of conservative practitioners who resist change'.
      Indeed where a deficiency exists, QI methodology would have us look beyond an
      individual or single group towards the processes that create the opportunity for
      deficiency to occur. Within the current context, such processes are inherently
      structural and are historically established within the health industry. A
      solution to this problem requires organizational commitment and a period of
      analysis as well as the transformation of attitudes and practices. Organizational
      commitment will take the form of adequate resourcing and a developmental approach
      to organizational change. Internal professional change (perhaps guided by
      organizational development) must address the interface between the 'medical
      profession' and the broader group of professional health-care providers.

PMID- 9631353
TI  - An analysis of patient complaints in an observation unit.
AB  - All complaints relating to patients treated in a 20 bed observation unit of a
      large teaching hospital over a 26-month period are reviewed. From May 1994 to
      July 1996, 11,042 patients were admitted to the observation unit. During this
      period there were 28 patient complaints. These complaints consisted of staff
      attitude/behavior (42.9%), discharge processes (25%), environmental concerns
      (17.9%), difficulties with diagnostic investigations (10.7%), and miscellaneous
      issues (3.6%). The type and frequency of complaints were similar to those
      received in other areas of the hospital, although the profile of complaints was
      different to those commonly experienced in the emergency department. Observation
      units are frequently considered to be an extension of the emergency department.
      Patient complaints received in relation to care received in an observation unit
      are similar in nature to those recorded in inpatient units as opposed to those
      received in emergency departments.

PMID- 9631354
TI  - What is your diagnosis? Tetanus.

PMID- 9631355
TI  - Complications with non-endoscopic percutaneous gastrostomy in 31 cats and 10
      dogs: a retrospective study.
AB  - Percutaneous gastrostomy tubes were placed non-endoscopically in 31 cats and 10
      dogs using either a rigid insertion tube (n = 13) or an Eld gastrostomy tube
      applicator (n = 28). Tubes were placed successfully in 38 of the 41 animals and
      the consequent feeding was of therapeutic benefit to 31 of the animals. Six of 41
      died or were euthanased for reasons unrelated to gastrostomy. In four cases (10
      per cent), gastrostomy failed with respect to correct tube placement or tube
      feeding. Overall complications occurred in 18 of 41 animals. Severe procedural
      complications occurred in two cats; a cardiorespiratory arrest during pharyngeal
      manipulation and erroneous tube placement through the distal oesophagus. Moderate
      late complications included peristomal food leakage (n = 2), peristomal abscess
      (n = 2) and pyloric outflow obstruction by a migrated tube (n = 1). Complications
      associated with the feeding procedure, nausea and vomiting (n = 3), led to
      aspiration pneumonia in one case.

PMID- 9631356
TI  - Treatment of canine nasal aspergillosis with a new non-invasive technique.
      Failure with enilconazole.
AB  - A new, non-invasive technique recently described for the treatment of canine
      nasal aspergillosis was performed on four dogs. The antimycotic agent used was a
      10 per cent enilconazole suspension, with the drug left in situ for a period of
      one hour. None of the dogs responded to single treatment. One dog died from an
      acute septic response secondary to pyelonephritis and bacterial endocarditis
      eight days after a second treatment. A second dog responded completely to a
      second treatment and remained free of fungal disease for a follow-up period of 11
      months. In the remaining two dogs, extensive and profuse fungal growth was seen
      on rhinoscopic re-examination. Conventional treatment, with tube implantation
      into the frontal sinuses and nasal irrigation for two weeks, was performed.
      Successful resolution of infection was obtained. Although the new, non-invasive
      technique was simple to carry out and well tolerated by the dogs, instillation of
      10 per cent enilconazole appears to have poor therapeutic efficacy and
      exacerbated fungal growth in two of the animals.

PMID- 9631357
TI  - Enthesiopathy of the short radial collateral ligaments in racing greyhounds.
AB  - In a radiographic survey of the carpi of 100 racing greyhounds there was a 14 per
      cent incidence of enthesiopathy of the origin of the straight part of the short
      radial collateral ligament. Enthesiopathy was not identified as a clinical
      problem in any case, nor was there historical evidence of any adverse effect on
      performance.

PMID- 9631358
TI  - Naturally acquired leptospirosis in 36 dogs: serological and clinicopathological
      features.
AB  - Case records of 36 dogs with confirmed leptospirosis diagnosed at the New York
      State College of Veterinary Medicine from 1980 to 1995 were reviewed
      retrospectively, and clinical, serological and pathological findings were
      recorded to characterise the epidemiology of this disease in upstate New York.
      Titres were directed predominantly against serovars grippotyphosa and/or pomona
      in 31 of 34 dogs. Convalescent titres were measured for 53 per cent of dogs. The
      most common clinical presentation was acute renal failure. Increased liver enzyme
      activity was documented in 22 of 36 dogs. It is clear from this study that
      Leptospira pomona and grippotyphosa are important pathogens capable of causing
      severe renal and hepatic injury in dogs.

PMID- 9631359
TI  - Treatment of Trombicula autumnalis infestation in dogs and cats with a 0.25 per
      cent fipronil pump spray.
AB  - To evaluate the efficacy of fipronil in controlling trombiculid infestations, 18
      dogs and three cats infested with Trombicula autumnalis larvae were treated
      monthly from examination to the end of the Trombicula season (range one to four
      months) with a 0.25 per cent fipronil spray applied to the whole body, with
      particular emphasis on the feet, face, ears, perineum and tail. No other
      antiparasite measures were used. Follow-up was by clinical examination and
      telephone interview until the end of the Trombicula season (range one to four
      months). No adverse effects were seen. Monthly treatment controlled trombiculids
      in 15 dogs. In two dogs localised pedal reinfestations were controlled with
      additional local application of fipronil to the feet every 14 days. In one dog
      therapy was of no benefit. In the three cats, treatment was initially effective,
      but generalised infestations recurred after seven to 10 days. Fipronil is a safe
      and effective treatment for trombiculid infestations in dogs. Residual activity
      lasts for 14 to 30 days. Further studies are required to examine the apparent
      short duration of efficacy in cats.

PMID- 9631360
TI  - Sciatic perineal hernia in two dogs.
AB  - A sexually intact, male Chihuahua and a spayed female poodle were presented with
      left perineal masses. The masses were identified as perineal hernias by rectal
      palpation. Surgical exploration of the perineal region in each dog revealed
      retroperitoneal fat protruding between the sacrotuberous ligament and the
      coccygeus muscle (sciatic perineal hernia). The hernias were repaired using
      modifications of the standard or internal obturator flap herniorrhaphies. The
      levator ani muscle was grossly and histologically normal in the Chihuahua and
      grossly normal in the poodle. No short- or long-term complications were reported
      in either case. The management of sciatic perineal hernia is similar to the more
      common caudal perineal hernia.

PMID- 9631361
TI  - Unusual congenital portosystemic communication resulting from persistence of the
      extrahepatic umbilical vein.
AB  - An unusual congenital portosystemic shunt was identified in one dog and two cats
      with clinical signs and laboratory evidence of hepatic dysfunction. In all the
      animals, the abnormal vessel arose from the portal system between the left medial
      and quadrate liver lobes and travelled within the falciform fat, exiting the
      abdomen through the caudal ventral left diaphragm. The intrathoracic course of
      these vessels was not established. The anatomical location of this anomalous
      vessel may have hindered attempts at ultrasonographic identification since it was
      not visualised before surgery in any of the animals. In addition, while the
      anatomical location of the vessel may facilitate rapid identification and
      surgical attenuation, it could predispose the vessel to trauma during the
      coeliotomy approach. It is hypothesised that this form of portosystemic
      communication results from failure of a portion of the left umbilical vein to
      degenerate during embryogenesis. This is in contrast to other forms of congenital
      extrahepatic portosystemic shunt that are presumed to be developmental errors
      resulting in an abnormal communication between the embryonic vitelline and
      cardinal venous systems. The prognosis for animals with the vascular anomaly
      reported here is probably similar to that for animals with other forms of
      congenital portosystemic shunt.

PMID- 9631362
TI  - Multiple myeloma with associated polyneuropathy in a German shepherd dog.
AB  - A 12-year-old female, neutered German shepherd dog developed progressive hindlimb
      followed by forelimb ataxia leading to tetraplegia. Neurological examination
      suggested lower motor dysfunction. Biochemical evaluation revealed a monoclonal
      hypergammaglobulinaemia, hypoalbuminaemia and hypercalcaemia. Multiple lytic
      lesions were identified radiographically in numerous bones. A bone marrow
      aspirate confirmed the diagnosis of multiple myeloma, with large numbers of
      plasma cells seen in clusters. An electromyogram revealed positive sharp waves
      and fibrillation potentials in the skeletal muscles of the limbs, suggesting a
      polyneuropathy. The dog was treated with chemotherapy using melphalan and
      prednisolone. Both the hypergammaglobulinaemia and the polyneuropathy resolved
      and the dog had normal motor function four weeks after commencing treatment.
      Polyneuropathy may occur as a paraneoplastic syndrome secondary to myeloma, and
      in this case was reversible following treatment of the underlying disease.

PMID- 9631363
TI  - Malignancy associated changes in bronchial epithelial cells and clinical
      application as a biomarker.
AB  - A total of 74 bronchial brushing specimens, 24 from patients with advanced stage
      cancer, eight from patients with CIS, 31 from patients with atypical metaplasia
      and 11 from normal subjects were examined for the existence of malignancy
      associated changes (MAC). Conventional fiberoptic bronchoscopy and fluorescence
      endoscopy was carried out on every case. Each case was classified according to
      the highest grade of abnormality diagnosed by bronchial biopsy of the suspect
      areas. During the endoscopy examination, a bronchial brushing specimen was
      obtained from a visually normal area very remote from the abnormal area as
      possible such as the opposite lung or another lobe. The bronchial brushing
      specimens were fixed, mounted and stained by a DNA specific method and
      approximately 1500 images of individual nuclei per case were captured by an
      automated high resolution image cytometry. For each of these images, more than
      100 nuclear features such as size, shape and chromatin spatial organization were
      calculated. Discriminant function analysis revealed nuclear features which
      differentiated between normal bronchial cell nuclei from the normal subjects and
      ostensively normal nuclei (MAC cell nuclei) from the lung cancer patients. The
      best discrimination was achieved when the frequency of individual cells
      expressing MAC was 50% or greater. With this threshold, 75% of the patients with
      invasive cancer and CIS were correctly classified. Fifty percent of those with
      severe or moderate atypia and 35% with mild atypia were also MAC positive. The
      frequency of cells expressing MAC also increased as the degree of abnormality of
      the groups increased. MAC may be a useful criterium to determine biological
      behavior of the intra-epithelial (pre-invasive) neoplasia.

PMID- 9631364
TI  - The contribution of 18F-fluoro-2-deoxy-glucose positron emission tomographic
      imaging to radiotherapy planning in lung cancer.
AB  - A retrospective analysis was performed to determine whether coronal thoracic
      [18F]fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) scans, if
      viewed at the time of radiotherapy (RT) planning, would have influenced the
      anterior-posterior (AP) RT volumes that were administered to a group of
      unoperated lung cancer patients. Viewing of PET and diagnostic images enabled a
      qualitative assessment of whether abnormal thoracic PET activity was present in
      areas regarded as normal by diagnostic imaging; this would, therefore, have
      influenced the RT volume if done prospectively. Additionally a method of
      graphical co-registration was devised to quantitate the adequacy of coverage of
      each patient's abnormal PET activity by his/her actual RT field. Of 15 patients
      analyzed, 26.7% (four patients) would have had their RT volume influenced by PET
      findings, highlighting the potential value of PET in treatment planning.

PMID- 9631365
TI  - The value of lung function measurements for the assessment of chemotherapy in
      lung cancer patients.
AB  - A retrospective analysis of lung function changes in lung cancer patients (NSCLC
      and SCLC) receiving various chemotherapy regimens, showed--statistically non
      significant--improvements of some parameters in responders, especially FEV1 and
      VC (mean increase of 230 and 310 ml after three cycles of chemotherapy), while
      stable values were observed in non responders. The majority of patients suffered
      from a decline in diffusing capacity, irrespective of response. Although the
      specificity and sensitivity of this functional evaluation are too low to allow
      lung function parameters to replace more conventional staging procedures,
      improvement in lung function in responders might indicate that chemotherapy can
      improve quality of life.

PMID- 9631366
TI  - Phase II study of paclitaxel (Taxol) and ifosfamide (Holoxan) in inoperable non
      small-cell lung cancer.
AB  - A total of 27 patients with advanced previously untreated non-small-cell lung
      cancer were treated with paclitaxel and ifosfamide. The starting dose of
      paclitaxel was 175 mg/m2 given for 3 h by intravenous infusion on day 1.
      Ifosfamide 4 g/m2 was given for 4 h by intravenous infusion on day 2. Dosage of
      the two drugs was modified according to nadir white blood count after each cycle.
      Involved in the treatment were 17 males and 10 female patients. The median age
      was 61 years (range 47-71 years) and the median Karnofsky performance status was
      70% (range 60-90%), 13 cases were stage IIIb and 14 cases were stage IV. One case
      was not evaluable due to lost follow-up after a single dose of chemotherapy.
      There were five cases not determined due to a timing error. Of 21 evaluable
      cases, eight achieved partial response (PR 38%, confidence interval 18.1-61.5%),
      seven achieved stable disease, two had a minor response. The median survival time
      of the whole group was 255 days (range from 38 to 567 days). The major toxicities
      were myalgia; arthralgia and neuropathies. Throughout the study, only three cases
      (15%) were treated at dose level 0. After the first cycle, 18 cases were treated
      at dose level 1, after a second cycle, 13 cases were treated at dose level 2.
      Three cases with grade 3 leukopenia were seen at dose level 0. At dose level 1,
      two cases had grade 3 leukopenia. At dose level 2, four episodes of grade 3
      leukopenia were noted. It is concluded that paclitaxel can be combined safely
      with ifosfamide at these dosage levels. The response rates were comparable to the
      other chemotherapy combination in advanced non-small-cell lung cancer. The
      survival results were acceptable and comparable to the cisplatin-containing
      regimen. This study indicates that combinations of paclitaxel and/or ifosfamide
      with other agents, such as gemcitabine and vinorelbine, should be explored.

PMID- 9631367
TI  - A survey analysis of thoracic surgeons in Turkey on mediastinal investigation of
      lung cancer.
AB  - A total of 59 general thoracic surgeons of 21 academically based thoracic surgery
      centres in Turkey were surveyed to identify the attitudes toward mediastinal
      investigations in patients with lung cancer. The surgeons were asked 16 questions
      in five separate groups by survey questionnaire. Analyses of the replies were as
      follows: Group I: 37 (62.7%) of the respondents were working in 11 centres where
      > 100 patients are admitted or referred for lung cancer annually. More than 50
      thoracotomies are performed for lung cancer annually in one third of the centres
      in which 28 (47.5%) respondents work. Group II: Among the diagnostic methods for
      evaluating mediastinum, surgeons most commonly used the computed tomography,
      mediastinoscopy, mediastinotomy and scalene lymph node biopsy. Invasive staging
      was done routinely by ten (16.9%) and selectively by 44 (74.6%). Group III: In
      patients with preoperatively histologically proven ipsilateral mediastinal lymph
      node involvement, 39 (66.1%) were advocates of operating. When the lymph node(s)
      was found to be positive at operation, 33 of them (55.9%) gave the decision with
      respect to the number, size and presence of pericapsular invasion of the node(s),
      while 24 (40.7%) decided to perform lung resection in every situation. Group IV:
      All accessible mediastinal nodes were said to be removed at thoracotomy by 37
      (62.7%). Group V: Currently available methods for mediastinal investigation were
      found to be partially sufficient by 37 (62.7%). The most important factor in
      predicting postoperative survival was selected as nodal status by 27 (45.8%). It
      is noticed that nearly all thoracic surgeons in Turkey perform mediastinal
      investigation preoperatively in patients with lung cancer, however, the impact of
      lymph node status needs to be more commonly appreciated.

PMID- 9631368
TI  - A survey of the ethical considerations in randomised trials for lung cancer.
AB  - BACKGROUND: In order to promote a more productive debate on the ethics of
      randomised clinical trials (RCTs), we present a survey on the ethical aspects of
      published RCTs for lung cancer. METHODS: Data from 92 published reports of RCTs
      for lung cancer, as identified from the Cancerlit 1993-1995 database were
      supplemented by a questionnaire mailed to the authors of those publications. The
      analysis focused on respect of autonomy, non-maleficence, beneficence, and
      justice as the ethical principles applicable to society, patients in trials,
      patients not included in RCTs and physicians. ETHICAL ANALYSIS: The benefits to
      society include an objective evaluation of new treatments. The principle of
      autonomy was often violated for patients who were inadequately informed about the
      disease or about RCT. In some trials with prolonged recruitment, the principle of
      non-maleficence was not fully respected since patients continued to be randomised
      in spite of an obvious advantage of one of the treatments. When compared to those
      not included in a trial, patients in RCTs were reported to benefit from more
      precise standards, superior quality assurance of diagnostic and therapeutic
      procedures, more attention from the physician, easier appointments and easier
      access to hospitalisation. However, these benefits diminish patients' autonomy
      and lead to injustice towards patients not included in the trials. While benefits
      to physicians were usually modest and in proportion to their contribution, an
      influence upon their autonomy cannot be excluded. CONCLUSION: More attention to
      the aforementioned ethical caveats of RCTs should alleviate the ethical costs and
      might also bring more patients into future trials.

PMID- 9631369
TI  - Primary adenoid cystic carcinoma in the lung: report of two cases and therapeutic
      considerations.
AB  - Primary adenoid cystic carcinoma in the lung is an uncommon disease, which is
      regarded as a slow growing low-grade malignancy. However, this disease has a high
      risk of incomplete resection because of its unique histological invasion
      patterns. The cases of two patients who recently underwent surgery for adenoid
      cystic carcinoma in the lung are reported. Both patients received postoperative
      radiotherapy treatment as a follow-up to a histologically incomplete resection.
      Both patients have survived for 51 months and 7 months, respectively, with no
      recurrence. Postoperative radiotherapy is an acceptable treatment of choice to
      control residual lesions and provides long-term survival even in cases of
      incomplete resection.

PMID- 9631370
TI  - Clinical prognostic factors in surgically treated stage IIIA-N2 non-small cell
      lung; an analysis of literature.

PMID- 9631371
TI  - Distribution of deoxynivalenol in barley kernels infected by Fusarium.
AB  - Deoxynivalenol (DON) in concentration range 0.1-156.6 mg/kg, was found in 48
      samples of barley kernels collected from heads with visible symptoms of head scab
      after inoculation in a field with Fusarium culmorum and Fusarium graminearum.
      Four fractions of the kernels were collected according to their size: > 2.8 mm
      (I); < or = 2.8-2.5 mm (II); > 2.5-2.2 mm (III) and < 2.2 mm (IV). In plants
      infected with Fusarium (when compared to the control) number of kernels in the
      fraction of the largest kernels (> 2.8 mm) decreased from 38% to 18%, while in
      small kernels (fractions < 2.5-2.2 mm and < 2.2 mm) numbers increased
      respectively from 16 to 22% and from 14 to 28%. Average level of DON
      concentration in these fractions was as follows: (I) 3.5 mg/kg--(4%); (II) 9.1
      mg/kg--(16%); (III) 35.5 mg/kg--(29%) and (IV) 43.3 mg/kg--(51%). The highest DON
      accumulation was observed in fraction of small (< 2.5 mm) kernels. The fraction
      contributed from 77% up to 94% of total DON content in kernels with low (< 2
      mg/kg) and high (> 100 mg/kg) contamination level, respectively. These results
      indicate that as well level of samples contamination with DON as human and animal
      health risk in consequence can be reduced by kernels selection (according their
      size) followed by rejection of the smallest kernels fraction.

PMID- 9631372
TI  - African yam bean hull chemical composition and its effects on rat's mineral
      retention, serum biochemical components and enzymatic activities.
AB  - The influence of yam bean hull on rat's mineral metabolism, serum composition and
      enzymatic activities was investigated. The chemical composition of the bean's
      hull shows a reasonably high crude protein (11.4%) but very low contents of crude
      fat (2.6%), phytic acid (82 mg/100 g) and phytin-phosphorus (23 mg/100 g). K and
      Ca are the major minerals present in yam bean hull. The hull, rich in cell wall
      polysaccharides, is composed of cellulose (35.4%), non-cellulose fractions made
      of pectin and hemicellulose put together (41.9%) and lignin (3.6%). The growth
      and feed conversion efficiency of rats fed yam bean hull diet were significantly
      better than rats fed pure cellulose and cellulose-free diets. Conversely, the
      metabolizable energy of yam bean hull diet (16.4 MJ/kg) was significantly (p <
      0.05) lower than that of either cellulose-free (17.8 MJ/kg) or pure cellulose
      diet (17 MJ/kg). The retention of the minerals examined, except for Ca, was lower
      when the hull was included in diet as compared to the control (fibre-free) diet.
      The fibre containing diets decreased serum cholesterol, glutamic oxaloacetate
      transaminase (SGOT) and glutamic pyruvate transaminase (SGPT). Yam bean hull had
      no effect on packed cell volume and serum total protein.

PMID- 9631373
TI  - Aluminium determination in foods by using spectrophotometric oxine and flame AAS
      methods.
AB  - Results of aluminium determinations obtained by employment of N2O-C2H2 flame AAS
      method and spectrophotometric oxine (SO) method in teas, fresh leaves of celery
      and some other food samples were compared. The samples were digested for few
      hours in teflon beakers with use of a mixture of concentrated acids (H2SO4 + HNO3
      + HCIO4), and then transported for final destruction into platinum dishes for
      ashing. The obtained stock sample solutions were used for examination by both
      methods. The accuracy was checked with recovery test of aluminium added to the
      samples before decomposition. With employment of AAS-method 83.3% to 100% (mean
      94.2 +/- 8.1%) of added aluminium was recovered, and in the SO method from 86.4
      to 109.3% (mean 98.6 +/- 5.2%). Great care is necessary for preparation of the
      blank. Food products containing higher levels of aluminium (i.e. teas and herbs)
      can be determined directly by the employed AAS-method using 1-2 g of samples for
      decomposition, while foods containing low levels of aluminium need use of larger
      samples for decomposition (i.e. 5-10 g or even more than 50 g in the case of
      strawberry or fresh leaves of celery) and the obtained ash should be dissolved to
      as low as possible of final volume of stock sample solution. The SO method is
      about 7 to 10 times more sensitive than the nitrous-oxide flame AAS method and
      enable to determined about 2.5 micrograms of Al per sample in form of oxine
      complex extracted into a 5 ml chloroformic phase. In the case of AAS-method the
      lowest determined level of aluminium amounted about 6 micrograms/ml of the
      examined sample solution. The results of both methods are strong correlated, as
      it is showed by the correlation coefficient (r = 0.97) at the level of
      significance alpha = 0.05.

PMID- 9631374
TI  - [Intravenous valproic acid administration in status epilepticus].
AB  - Despite progress in controlling status epilepticus (SE), a search is still in
      progress for a drug--a single agent--that would successfully and safely interrupt
      this life-threatening situation. Valproate (VPA) has been used in control of SE
      since the 1970s, yet only in the late 1980s was VPA first administered
      intravenously, with good results. Twenty adult patients in acute or static SE
      with generalized tonic-clonic seizures (GTCS) or simple partial motor seizures
      were administered VPA (Depakine Injectable 400 mg, Sanofi Winthrop) in a bolus
      dose of 15 mg/kg body weight and then 30 min later as a continuous infusion of 1
      mg/kg/h for 24 h. The therapeutic effect was evaluated depending on the type of
      SE, its aetiology and the time lapse between seizure onset and drug
      administration. Response latency time (time between drug administration and
      seizure cessation) was considered as index of therapy success. SE was interrupted
      in < 30 min in 80% of cases (88.8% of patients with GTCS and 72.7% of those with
      partial simple motor seizures). A better effect was achieved in patients with
      static SE and in patients in whom SE lasted < 3 h before treatment. In 60% of
      patients with interrupted SE, the response latency time was < 20 min. The results
      indicate high success of VPA in SE control.

PMID- 9631375
TI  - [Combined therapy with lamotrigine++ in primary generalized epilepsy in adult
      patients].
AB  - An attempt is presented to use Lamictal (lamotrigine) produced by GlaxoWellcome
      in 30 patients with primary generalized epilepsy, already taking one of
      antiepileptic drugs, but refractory to this treatment. The patients were treated
      with carbamazepine (Amizepin) 600-1200 mg daily or with sodium valproate
      (Depakine) 1200-1600 mg daily. In the course of add-on therapy patients were
      receiving in first 4 weeks increasing doses of Lamictal starting from 50 mg or 25
      mg (patients treated with sodium valproate). Maintenance dose of lamotrigine was
      200 mg daily in two divided doses. The results of first three months of the
      treatment were generally positive. Half the patients experienced a reduction in
      seizure count by more than a half, what testify the Lamictal is a valuable
      medication in the treatment of primary generalized epilepsy. The observed side
      effects had transitory character.

PMID- 9631376
TI  - [Cardiologic risk factors for stroke].
AB  - The aim of this work was to investigate the cardiologic risk factors for stroke.
      232 patients were studied. All of them had a stroke. There were 133 males and 99
      females. The most often observed cardiologic risk factor for stroke was ischaemic
      heart disease, which was present in 48.2% of all the cases. Usually ischaemic
      heart disease was observed as stable angina pectoris (34.4%) and past cardiac
      infarction (9.9%). Dysrrhythmia and conduction abnormalities were present in
      46.1% of cases, mostly as premature ventricular beats (13.4%) and atrial
      fibrillation and atrial flutter (12.5%). Congenital and acquired heart diseases
      (11.6%) and chronic circulatory failure (15.9%) were recognized in lower per cent
      of the cases. The assessments of other authors and our observations evidence the
      relevance of cardiologic risk factors in stroke.

PMID- 9631378
TI  - [Motor segmental conduction times for extensor digitorum brevis muscle: method
      and normative values].
AB  - Electrical stimulation of the peroneal nerves (60 nerves) and magnetic
      stimulation of the roots (L5) and motor cortex were performed on 30 normal
      controls. The muscle responses and F wave (peripheral stimulation) were recorded
      from extensor digitorum brevis muscle (60 muscles). The parameters of examined
      potentials were measured and the central, root, peripheral motor conduction
      times, were estimated. The normative values were established as well as formulae
      of linear regression within the observed correlations with height. The method may
      be used for electrophysiological diagnosis of patients with motor pathway
      impairment on the different levels.

PMID- 9631377
TI  - [Median nerve electrophysiological assessment in amyotrophic lateral sclerosis].
AB  - Our material comparises 105 patients (62 men and 43 women) aged 26-73 years with
      amyotrophic lateral sclerosis (ALS). EMG examination confirmed the diagnosis of
      multilevel lesion of spinal motor neurons. Clinically, 94 of them had classical
      ALS, 3 had primary bulbar palsy (PBP), 6 had primary motor spinal atrophy (PSMA),
      and 2 had primary lateral sclerosis (PLS). Disease duration was 18.1 month, on
      the average, ranging from 2-60 months. In all patients motor and sensory nerve
      conduction was studied in median, peroneal and sural nerves. Conduction velocity,
      distal latency, F-wave latency of motor nerves, amplitude of M response and of
      sensory potentials were evaluated. Abnormalities were found most often in the
      motor fibres of median nerve: lowering of the M response amplitude in 44% of
      nerves studied, slowing of conduction velocity and elongation of distal latency
      in ca. 30%, elongation of F-wave latency in 27%. In the peroneal nerve the
      changes were less frequent: 38%, 21%, and 3%, respectively. They were also less
      marked. In the sensory fibres of median nerve slowing of conduction velocity was
      found in 25% of nerves, in sural nerve in 11%. Some slight decrease of amplitude
      of sensory potentials was seen in those nerves. The results obtained indicate a
      possibility of peripheral nerve lesion in the course of ALS which must be
      remembered in clinical diagnosing.

PMID- 9631379
TI  - [The influence of premedication with diclofenac or pethidine on pain and postop
      treatment in lumbar discopathy].
AB  - 206 patients scheduled for spinal surgery (lumbar discopathy) were randomly
      premedicated with diclofenac, pethidine, diazepam or hydroxizine. The frequency
      of persisted postoperative pain was evaluated from the 3-ed. postoperative day to
      the end of hospitalisation--as the need for additional concomitant treatment with
      dexamethasone and intravenous analgesics. The frequency of persisted pain was
      significantly decreased in patients premedicated with diclofenac (together with
      diazepam) before spinal surgery (limited to fenestration) in comparison to
      patients premedicated with pethidine. The pre-emptive analgesic effect of
      diclofenac was even more evident in patients treated with non-steroidal anti
      inflammatory drugs (NSAID) before surgery, but was not observed in patients after
      more traumatic surgery (laminectomy) premedicated with diazepam. The results are
      supporting the important role of NSAID given before surgery to decrease the
      frequency of persisted pain after spinal surgery (limited to fenestration), in
      patients treated with NSAID.

PMID- 9631380
TI  - [Preliminary results of the treatment of occlusive hydrocephalus in children by
      endoscopic techniques].
AB  - The group of 20 patients with the preliminary diagnosis of occlusive
      hydrocephalus were treated by neuroendoscopic technique. Ten
      ventriculocystocisternostomies in cases with third ventricle arachnoid cysts
      accompanied by hydrocephalus, 9 ventriculostomies, and 1 ventriculostomy with
      fenestration of posterior fossa cystic lesion were performed. It was proven that
      the neuroendoscopic procedures were effective in 17 cases (85%) in the 10 months
      mean follow-up period of the study group. With no mortality, transient surgical
      complications were observed in 5 cases (25%). In 3 cases, inefficacy of the
      method was caused by false preoperative evaluation, and inappropriate surgical
      technique.

PMID- 9631381
TI  - [Post-traumatic cerebrospinal rhinorrhea managed surgically. Clinical analysis of
      cases].
AB  - 47 patients was treated surgically for posttraumatic cerebrospinal fluid
      rhinorrhea between 1977 and 1996 in the Department of Neurosurgery in Poznan.
      Cerebrospinal fluid fistula developed after road accident, less often because of
      assault, fall etc. Frontobasal fracture usually caused rhinorrhea and was
      verified by plain X-rays, computed tomography and magnetic resonance. Indications
      to early surgery were rhinorrhea coexisting with intracranial haematoma or
      pneumocephalus, optic nerve lesion, the persistent or recurrent rhinorrhea and
      meningitis. The authors present surgical methods and postoperative complications.
      Good outcome was in 86%.

PMID- 9631382
TI  - [Brain stem auditory evoked potentials in brain death state].
AB  - The authors studied auditory brainstem evoked potentials (BAEP) in 27 organ
      donors aged 40 to 68 years treated in neurosurgery units in Szczecin and
      Grenoble. Abnormal results were found in all cases. In 63% of cases no evoked
      action potentials were obtained, in 34% only the 1st wave was obtained, and in
      two cases evolution was observed with activity extinction. The authors believe
      that in the process of shaping of BAEP morphotic extinction begins from the later
      waves to earlier ones in agreement with the rostrocaudal direction of extinction
      of the functions or brain midline structures, and in a single study various
      findings may be obtained.

PMID- 9631383
TI  - [Neurologic borreliosis].
AB  - Any headache in the course of Lyme disease could be an early manifestation of
      invasion of the CNS by spirochaetes. The most characteristic symptoms of early
      neuroborreliosis are meningitis with cranial or peripheral neuropathies connected
      with radiculopathies, less common are encephalitis and myelitis, neuropathies,
      polyneuropathies, encephalopathies. Encephalomyelitis is the most serious form of
      neuroborreliosis. From the pathophysiologic point of view all cranial and
      peripheral neuropathies are forms of mononeuritis multiplex. Encephalopathy is
      due to neuroimmunomodulators, like lymphokins and or by toxico-metabolic effect
      could be connected with each form of systemic borreliosis. Certain diagnosis of
      neuroborreliosis is based on culturing of B. burgdorferi from CSF, detection of
      specific antispirochaetal antibodies produced in the subarachnoid space,
      detection of activated lymphocytes B producing specific antibodies, detection in
      CSF of other antigens of B. burgdorferi or DNA sequences.

PMID- 9631384
TI  - [Apolipoprotein E function in the nervous system].
AB  - Human ApoE is a plasma and cerebrospinal fluid protein that serves as a ligand
      for low density lipoprotein receptors and, through its interaction with these
      receptors, appears to be involved in the transport of cholesterol and other
      lipids among the nervous cells. ApoE is synthesized by astrocytes in brain and by
      macrophages in peripheral nerves during the repair response to tissue injury and
      regeneration. In the nervous system ApoE may also be involved in processes
      unrelated to lipid transport, the processes that were completely unsuspected
      until very recently and have led to the link between ApoE and the
      neurodegenerative disorder--Alzheimer's disease. The lipoprotein has been found
      in association with cerebral amyloid deposits and the presence of the epsilon 4
      allele constitutes a major genetic risk factor for Alzheimer's disease but does
      not influence the rate of cognitive decline. It has been shown that ApoE4
      promotes fibrillogenesis in vivo and in vitro from amyloid beta peptide and ApoE3
      binds to tau protein slowing the initial rate of its phosphorylation and self
      assembling into paired helical filaments. This review summarizes the data leading
      to this conclusion and discusses possible mechanisms: of ApoE involvement based
      on recent biochemical studies. The clinical application of ApoE level estimation
      in cerebrospinal fluid and phenotyping is presented.

PMID- 9631385
TI  - [Brain barriers. Part II. Blood/cerebrospinal fluid barrier and cerebrospinal
      fluid /brain tissue barrier].
AB  - Brain has its own unique and effective protection system that controls the
      process of active transport of chemical substances from blood to neurons and
      cerebrospinal fluid. The above mentioned system is called the blood brain
      barrier. As far as morphology is concerned the barrier consists of several
      membranes isolating the following compartments of the intracranial space: brain
      tissues, blood and cerebrospinal fluids. One of those membranes-blood/brain
      tissues barrier, has been described in the first part of this work. Structure and
      function of the blood/CSF barrier and CSF/brain tissues barrier are described in
      the second part.

PMID- 9631386
TI  - [Intraoperative facial nerve monitoring. Practical remarks].
AB  - OBJECTIVE: Even the most experienced surgeon may have difficulties in identifying
      and preserving the facial nerve, particularly when the operation is complicated,
      for example, by size and localization of tumour, trauma or anatomic variations.
      The aim of this study is to present indications, technics and interpretation of
      intraoperative facial nerve monitoring. METHODS: This study bases on literature
      review and our own experience in intraoperative facial nerve monitoring.
      CONCLUSIONS: Intraoperative facial nerve monitoring is helpful during excision of
      large and middle size acoustic neuromas, because preservation of facial nerve
      function improves with use of electrical monitoring. Intraoperative monitoring
      during other kinds of operation, which are likely to impact on the facial nerve
      may also be of benefit. This however, is hardly proved in the literature. Its
      seems, that electrical intraoperative monitoring is more sensitive than pneumatic
      motion detector system. Intraoperative monitoring is an adjunct, not replacement,
      to surgeon's experience and ability. The presence or absence of facial evoked
      responses must be interpreted within the context of surgical procedure, bearing
      in mind possibility the of false-positive and false-negative errors.

PMID- 9631387
TI  - [Diagnostic difficulties in a case of meningo-cerebral primary cryptococcosis].
AB  - A case of meningo-cerebral cryptococcosis is reported in a 34-year old women, in
      which no evidence of associated disease predisposing to disseminated infection
      could be demonstrated by clinical and autopsy examination. Diagnostic
      difficulties and presumable factors contributing to development of disease in the
      cases of so-called primary cryptococcosis are discussed.

PMID- 9631388
TI  - [Foix-Chavany-Marie syndrome].
AB  - A patient aged 54 with Foix-Chavany-Marie syndrome is described. The syndrome is
      characterized by facio-pharyngo-glossal diplegia with automatic-voluntary
      movement dissociation. The cause of the disease were bilaterally located infarcts
      within internal capsule.

PMID- 9631389
TI  - [A case of hemiballism in the course of hypertensive crisis].
AB  - Hemiballism was observed in a 54-year-old man with hypertensive crisis. Magnetic
      resonance and CT scan disclosed multifocal lacunar infarcts in the left thalamus
      and hypothalamus. Hemiballism in hypertensive crisis has not been frequently
      reported.

PMID- 9631390
TI  - [Idiopathic epidural lipomatosis of the vertebral canal].
AB  - Epidural lipomatosis is most frequently seen in patients on chronic steroid
      treatment. Only fourteen cases of idiopathic spinal epidural lipomatosis have
      been described. In this report we present an additional case of this condition in
      a 38 year-old man.

PMID- 9631391
TI  - [Central neurocytoma of the right parietal and occipital lobe. Case report].
AB  - Central neurocytoma is a rare tumour of the CNS. It typically occurs in
      intraventricular location in young adults. The authors describe central
      neurocytoma in a 17-year-old woman, which was situated unusually for this type of
      tumour in the brain parenchyma. In this paper radiological and histopathological
      picture is presented.

PMID- 9631392
TI  - [The response to the letter of Prof. J. Bidzinski regarding the article
      "Intracranial hematomas in the material of the department of the Department of
      Neurosurgery, Medical Academy in Lublin" (Neurologia, neurochirurgia polska,
      1996, 30, 617].

PMID- 9631393
TI  - Implications of maturation for viral gene delivery to skeletal muscle.
AB  - Different viral vectors have been analyzed as gene delivery vehicles to skeletal
      muscle for potentially therapeutic purposes. In this review, we evaluate the
      application of retroviral, adenoviral, and herpes simplex viral vectors to
      deliver genes to skeletal muscle and focus on the dramatic loss of viral
      transduction detected throughout muscle maturation. Recent results suggested that
      there are several factors involved in the reduced viral transducibility of mature
      skeletal muscle: muscle cells become post-mitotic in an early stage, the
      extracellular matrix develops into a physical barrier, and a loss of myoblast
      mediation occurs since myoblasts progressively become quiescent. Approaches to
      improve viral gene delivery to mature skeletal muscle may include the use of
      particular enzymes to increase the permeability of the extracellular matrix, the
      pre-treatment of the muscle with a myonecrotic agent to induce myoblast
      mediation, or the application of the myoblast-mediated ex vivo gene transfer.

PMID- 9631394
TI  - Confirmation that a T-to-C mutation at 9176 in mitochondrial DNA is an additional
      candidate mutation for Leigh's syndrome.
AB  - Among 80 patients with the clinical and brain imaging characteristics of Leigh's
      syndrome, 11 patients had a well-known mutation at nucleotide position (nt) 8993
      in mitochondrial DNA. In addition, three patients had a T-to-C mutation at nt
      9176 which had been described previously in only two brothers with bilateral
      striatal necrosis and one patient with Leigh's syndrome. In our three patients,
      one had the typical clinical characteristics of Leigh's syndrome from early
      infancy, and two had the later onset of neurological deficits. All had a slowly
      progressive course and basal ganglia abnormalities by neuroimaging. As nt 8993
      and 9176 are located in the ATPase 6 coding region, altered ATPase function may
      be one of the enzyme abnormalities in Leigh's syndrome and other similar
      conditions with bilateral striatal necrosis.

PMID- 9631395
TI  - Myotubular myopathy: morphological, immunohistochemical and clinical variation.
AB  - Myotubular myopathy frequently presents in male infants with severe generalised
      muscular hypotonia and weakness associated with ventilatory insufficiency, and is
      diagnosed on biopsy by the presence of many fibres with central nuclei and
      mitochondrial aggregation. In a 6-year period, we have investigated five
      unrelated patients with clinical and pathological features suggesting an X-linked
      myotubular myopathy, including one female patient. In one male infant, a biopsy
      of vastus lateralis showed less than 2% centrally-nucleated fibres, while biceps
      brachii showed up to 15% centrally-nucleated fibres. Immunohistochemical
      expression of the neural cell adhesion molecule (CD56) was more intense in the
      biceps muscle than in vastus lateralis, while expression of desmin and vimentin
      was similar. Morphometric evaluation of tissue from each of the patients revealed
      a wide spread of values for the number of centrally-nucleated fibres per
      microscopic field, and variation in the extent of immunohistochemical expression
      of NCAM, utrophin, laminin alpha 5 chain, vimentin and HLA1 antigen. These
      variations in the manifestations of myotubular myopathy have not been previously
      described, and will need to be correlated with the increasing knowledge of the
      mutations in the MTM1 gene coding for myotubularin.

PMID- 9631396
TI  - Congenital myopathies with inclusion bodies: a brief review.
AB  - Based on morphological abnormalities, congenital myopathies can be classified
      into several categories: (1) enzyme histochemically abnormal appearance without
      structural pathology, e.g., congenital fibre type disproportion or congenital
      fibre type uniformity; (2) abnormally placed nuclei, e.g. myotubular and
      centronuclear myopathies; (3) disruption of normal intrinsic structures, largely
      sarcomeres, e.g. central cores and minicores; (4) abnormal inclusions within
      muscle fibres. Several such inclusions are derived from pre-existing structures,
      most notably rods or nemaline bodies. Other derivatives of Z-band material are
      cytoplasmic bodies and possibly related inclusions as spheroid bodies,
      sarcoplasmic bodies or Mallory body-like inclusions. These inclusions share
      accumulation of desmin, the muscle fibre-specific intermediate filament, and of
      other proteins, some of them physiological, but others quite abnormal. Inclusions
      without identified precursors are fingerprint bodies, reducing bodies,
      cylindrical spirals, and Zebra bodies. Experimental models and tissue culture
      reproduction are necessary to further clarify significance of these inclusions in
      congenital myopathy pathology.

PMID- 9631397
TI  - Merosin-deficient congenital muscular dystrophy with severe mental retardation
      and normal cranial MRI: a report of two siblings.
AB  - The evidence of severe structural brain abnormalities in association with severe
      mental retardation is characteristic in congenital muscular dystrophy (CMD) forms
      other than the 'classical' form. However, it seems that the nosology of CMD is
      not complete yet, as we have clinical, immunohistochemical and genetic data
      suggesting that there are other unclassified forms. Here we report two CMD
      siblings from a consanguineous family with partial merosin-deficiency in muscle
      biopsies, severe mental retardation and normal MRI of the brain. The disease was
      not linked to the LAMA2 gene (6q22-23) or to Fukuyama congenital muscular
      dystrophy (FCMD) (9q31-33). To our knowledge, such an association may constitute
      a new entity within the broad clinical spectrum of CMD.

PMID- 9631398
TI  - Charcot-Marie-Tooth disease--muscle biopsy findings in relation to
      neurophysiology.
AB  - Nine patients with Charcot-Marie-Tooth disease with reduced motor nerve
      conduction velocity (MNCV), i.e. type 1 (CMT1), demyelinating form, and nine
      patients with Charcot-Marie-Tooth disease with normal or near-normal MNCV, i.e.
      type 2 (CMT2), axonal form, were subjected to percutaneous muscle biopsy from the
      anterior tibial muscle in order to characterize histopathological abnormalities
      and evaluate differences between the two groups. Data from the biopsies were
      compared with those from 18 age- and sex-matched healthy controls. Muscle
      biopsies from the CMT1 patients exhibited angular atrophic fibres that were
      scattered or in small groups, findings commonly described as neuropathic. Muscle
      biopsies from the CMT2 patients exhibited atrophic fibres that were rounded or
      elongated in groups and hypertrophic fibres with central nuclei and fibre
      splitting. There were also increased amounts of connective tissue, 'whorled
      fibres', degeneration and signs of regeneration, findings commonly regarded as
      myopathic. In conclusion, muscle biopsies from patients with CMT1 and CMT2 showed
      markedly different histopathological abnormalities. Possible underlying
      mechanisms are discussed.

PMID- 9631399
TI  - Hereditary motor and sensory neuropathy Lom type in an Italian Gypsy family.
AB  - We describe a form of hereditary motor and sensory neuropathy (HMSN) affecting
      four siblings in an Italian family of Gypsy ethnic origin with both clinical and
      pathological findings very reminiscent of the HMSN Lom type (HMSNL), recently
      described in a group of Bulgarian Gypsies. Genetic analysis demonstrated linkage
      to chromosome 8q24 and conserved haplotypes in the HMSNL region, thus confirming
      that this is the first Gypsy family outside the Balkans suffering from the same
      disorder.

PMID- 9631400
TI  - Critical illness myopathy unrelated to corticosteroids or neuromuscular blocking
      agents.
AB  - Acute myopathy occurs in critically ill patients, receiving neuromuscular
      blocking agents or corticosteroids during intensive care hospitalisation. We
      report three patients with acute quadriplegic myopathy, two of whom were not
      exposed to corticosteroids or neuromuscular blocking agents. The first of these
      latter two patients had a history of generalised anoxia with coma related to
      surgery, complicated by multiple organ failure and sepsis. The second patient,
      suffering from acute leukaemia, developed sepsis and acute respiratory distress
      syndrome with the need for mechanical ventilation in the intensive care unit.
      Electrophysiological studies and muscle biopsy findings were consistent with the
      diagnosis of critical illness myopathy with loss of myosin filaments. Selective
      loss of myosin was confirmed by biochemical analysis of muscle. These findings
      demonstrate that acute myopathy with loss of myosin filaments may occur in
      patients with severe systemic illness without exposure to corticosteroids or
      neuromuscular blocking agents.

PMID- 9631401
TI  - LGMD 2E in Tunisia is caused by a homozygous missense mutation in beta
      sarcoglycan exon 3.
AB  - Four of the currently recognized autosomal recessive limb-girdle muscular
      dystrophies (LGMD type 2C-F) are caused by mutations in the genes encoding
      components of the sarcoglycan complex. LGMD 2C, caused by mutations in gamma
      sarcoglycan, is prevalent in northern Africa, especially in Tunisia, where this
      type of muscular dystrophy was originally described. Although the disease
      initially was assumed to be genetically homogeneous in this region, linkage to
      the alpha-sarcoglycan locus (LGMD 2D) has also been found. We have now identified
      the first Tunisian family with beta-sarcoglycanopathy (LGMD 2E), further adding
      to the genetic heterogeneity of autosomal recessive LGMD in this population.
      Direct sequencing of the beta-sarcoglycan gene revealed a homozygous mutation
      (G272-->T, Arg91Leu) in exon 3. This change affects the same arginine residue in
      the immediate extracellular domain of the protein that was mutated to a proline
      (G272-->C, Arg91Pro) in a Brazilian family with a severe form of the disease.
      Immunohistochemical analysis for the sarcoglycan complex demonstrates absence of
      the known components of the complex in both of these families. We postulate that
      the immediate extracellular domain of beta-sarcoglycan may be important for the
      assembly and/or maintenance of this complex, potentially mediated by disulfide
      bond formation to another sarcoglycan via the single cysteine residue in that
      domain.

PMID- 9631402
TI  - Commentary: extraocular muscle sparing in muscular dystrophy: a critical
      evaluation of potential protective mechanisms.
AB  - Muscles or muscle groups exhibiting responses to neuromuscular disease that are
      unlike those of other skeletal muscles may provide novel information about
      pathogenesis leading to improved treatment strategies. The author's laboratory
      studies the relationship between the unique phenotype of the extraocular muscles
      and their selective sparing or targeting in neuromuscular disease. This
      commentary evaluates the evidence for and against four hypotheses for the
      selective protection of extraocular muscle in Duchenne muscular dystrophy (DMD)
      and merosin-deficient congenital muscular dystrophy (CMD).

PMID- 9631403
TI  - Heterogeneity in chronic fatigue syndrome: evidence from magnetic resonance
      spectroscopy of muscle.
AB  - It has been shown previously that some patients with chronic fatigue syndrome
      show an abnormal increase in plasma lactate following a short period of moderate
      exercise, in the sub-anaerobic threshold exercise test (SATET). This cannot be
      explained satisfactorily by the effects of 'inactivity' or 'deconditioning', and
      patients with abnormal lactate responses to exercise (SATET +ve) have been found
      to have significantly fewer Type 1 muscle fibres in quadriceps biopsies than
      SATET -ve patients. We performed phosphorus magnetic resonance spectroscopy on
      forearm muscles of 10 SATET +ve patients, 9 SATET -ve patients and 13 sedentary
      volunteers. There were no differences in resting spectra between these groups but
      at the end of exercise, intracellular pH in the SATET +ve patients was
      significantly lower than in both the SATET -ve cases and controls (P < 0.03), and
      the SATET +ve patients also showed a significantly lower ATP synthesis rate
      during recovery (P < 0.01), indicating impaired mitochondrial oxidative
      phosphorylation. These observations support other evidence which indicates that
      chronic fatigue syndrome is a heterogeneous disorder, and confirms the view that
      some chronic fatigue syndrome patients have a peripheral component to their
      fatigue.

PMID- 9631404
TI  - Effect of vitamin B6 supplementation in McArdle's disease: a strategic case
      study.
AB  - A patient-blind study into the effect of a 10-week cessation of long-term vitamin
      B6 supplementation on B6 status and performance in McArdle's disease is reported.
      Muscle performance was assessed both subjectively and objectively by an ischaemic
      fatiguing protocol of the adductor pollicis muscle. Nine weeks after withdrawal
      of supplementation, vitamin B6 status had changed from adequacy to inadequacy and
      the force loss during the ischaemic fatiguing protocol had increased at all
      frequencies studied. The patient reported decreased exercise tolerance after 7
      weeks and by the tenth week was experiencing an increase in muscle cramps.
      Vitamin B6 status and muscle performance may be linked in McArdle's disease and
      there is potential for enhancement of performance by B6 supplementation.

PMID- 9631405
TI  - First meeting of the Duchenne Parent Project in Europe: Treatment of Duchenne
      Muscular Dystrophy. 7-8 November 1997, Rotterdam, The Netherlands.

PMID- 9631406
TI  - Neuromuscular disorders: gene location.

PMID- 9631407
TI  - Mitochondrial encephalomyopathies: gene mutation.

PMID- 9631408
TI  - Neurobiological bases of spatial learning in the natural environment:
      neurogenesis and growth in the avian and mammalian hippocampus.

PMID- 9631409
TI  - Neuromagnetic activity in the human left cerebral hemisphere concerning logical
      processing during auditory oddball stimulation.
AB  - The aim of this study was to examine the cortex during the logical processing of
      auditory information using a whole-cortex type dc-SQUID gradiometer. The task
      modified the normal auditory oddball paradigm to require the processing of simple
      logic before counting a rare stimulus mentally. Although the latency of P300 m
      did not change, a dipolar magnetic field pattern was observed over the left
      cerebral hemisphere at approximately 280 ms poststimulus before forming the field
      pattern of P300 m. The equivalent current dipole source was estimated to be
      medial to the N100 m source. It was suggested that the additional load of logic
      processing may activate Heschl's gyri in the left hemisphere.

PMID- 9631410
TI  - Novel splice variants of the voltage-sensitive sodium channel alpha subunit.
AB  - In this study, we have identified novel splice variants of the Na+ channel alpha
      subunit mRNA from cultured rat astrocytes and neuroblastoma cells. These splice
      variants are characterized by premature truncation or deletion of a segment in
      the third domain of the Na+ channel alpha subunit. The expression of three splice
      variants was upregulated by exposure to 1 mM dibutyryl cAMP in spinal cord
      astrocytes but not in cerebral astrocytes and in B50 and B104 neuroblastoma
      cells. The calcium ionophore 1 microM A23187, did not influence the expression of
      splice variants in either astrocytes or neuroblastoma cells. These findings
      suggest that spinal cord astrocytes may maintain a unique regulatory pathway that
      participates in the control of Na+ channel mRNA expression.

PMID- 9631411
TI  - Sublethal in vitro glucose-oxygen deprivation protects cultured hippocampal
      neurons against a subsequent severe insult.
AB  - Rat and gerbil hippocampus exposed to a sublethal period of ischemia becomes
      resistant to a subsequent period of lethal ischemia induced several days later, a
      phenomenon referred to as ischemic preconditioning. Here we describe ischemic
      preconditioning induced in vitro in cultured hippocampal neurons. Mixed
      neuroglial hippocampal cell cultures of 14-17 DIV were exposed to a combined
      glucose and oxygen deprivation (GOD). Cultures subjected to 90 min, but not 60
      min, of GOD showed extensive degeneration after a 1 day recovery period. An
      episode of 60 min of preconditioning GOD followed 1 and 2 days later by 90 min of
      GOD resulted in 40-60% protection. The data demonstrate that ischemic
      preconditioning can be mimicked in an in vitro hippocampal cell culture system.

PMID- 9631412
TI  - Protection by pyruvate and malate against glutamate-mediated neurotoxicity.
AB  - Pyruvate and malate (P/M) increase the contribution of mitochondria to neuronal
      calcium homeostasis. We have now found that cortical neuronal cultures utilize
      pyruvate preferentially over glucose. The supply of pyruvate and malate protects
      hippocampal and cortical neurons against delayed cell death occurring 24 h after
      glutamate exposure. High [Ca2+]i levels attained during and after glutamate
      exposure were reduced when neurons were incubated in the presence of P/M. At the
      single cell level, this was reflected in a decrease in the number of neurons that
      respond to glutamate with high rises in [Ca2+]i. The results suggest that the
      ability to prevent large increases in [Ca2+]i may underlie the beneficial effects
      of pyruvate and malate during glutamate excitotoxicity.

PMID- 9631413
TI  - Effects of 18-methoxycoronaridine on acute signs of morphine withdrawal in rats.
AB  - Ibogaine, an alkaloid found in the root bark of the African shrub Tabernanthe
      iboga, has been claimed to interrupt opioid dependence in humans; in animals, it
      has been shown to inhibit morphine self-administration and to attenuate signs of
      morphine withdrawal. However, ibogaine has some neurotoxicity, and because of
      this, efficacious and safer congeners of ibogaine have been sought, 18
      Methoxycoronaridine (18-MC), a novel iboga alkaloid congener, has been shown, in
      animals, to mimic the effects of ibogaine on morphine self-administration without
      producing any ibogaine-like neurotoxiticity. In the present study, 18-MC was
      shown to attenuate five of seven signs of morphine withdrawal in rats. The data
      suggest that 18-MC will ameliorate symptoms of opioid dependence in humans.

PMID- 9631414
TI  - Neuroprotective effects of a novel AMPA receptor antagonist, YM872.
AB  - Quinoxalinediones such as NBQX are neuroprotective in most models of cerebral
      ischemia but their poor solubility results in nephrotoxicity limiting their
      clinical utility. We have investigated the neuroprotective effects of a water
      soluble AMPA receptor antagonist, YM872, using two in vitro models. The viability
      of cortical cultures exposed to 400 microM AMPA for 15 min (16.4 +/- 2.6%; n =
      10) was significantly (p < 0.05) increased (84.7 +/- 4.6%; n = 6) with YM872 (10
      microM) in a concentration-dependent manner. Evoked post-synaptic response
      amplitudes in oxygen-glucose deprived hippocampal slices treated with 10 microM
      YM872 (3.5 +/- 0.3 mV; n = 27) were significantly different from untreated
      deprived slices (0.3 +/- 0.1 mV; n = 31, p < 0.05) and the CA1 neurons appeared
      viable using a confocal live/dead fluorescence assay with confocal microscopy.
      The neuroprotection seen with YM872 in vitro warrants further investigation in
      vivo.

PMID- 9631415
TI  - Polymorphism in the promoter region of the alpha 2A adrenergic receptor gene and
      mood disorders.
AB  - Alpha 2 adrenergic receptors are thought to play a crucial role in the etiology
      or treatment of mood disorders. Polymorphism(s) in the promoter region of the
      alpha 2 receptor may affect the gene expression and be associated with mood
      disorders. We studied the previously reported polymorphisms of the alpha 2A
      receptor gene at position-1291 in 114 healthy controls and 103 mood disorder
      patients. There was statistically no difference between controls and patients in
      either the genotype or the allele frequency. There was statistically no
      difference between the genotype and the clinical characteristics. Our results
      suggest there is no association between this polymorphism in the promoter region
      of the alpha 2A receptor gene and mood disorders.

PMID- 9631416
TI  - 5'-heterogeneity of the human excitatory amino acid transporter cDNA EAAT2 (GLT
      1).
AB  - TWO novel transcripts of the human excitatory amino acid transporter EAAT2 (GLT
      1) were cloned using PCR cloning techniques. Comparative sequence analysis of the
      5'-untranslated region (UTR) of five EAAT2 transcripts led to the definition of
      five putative 5'-untranslated exons that are combined in a variable manner.
      Alternative splicing is a likely mechanism for the 5' complexity of the EAAT2
      cDNA. The potential functional meaning of this finding such as differential
      expression of the EAAT2 transcripts in the central nervous system remains to be
      demonstrated.

PMID- 9631417
TI  - Diffusion heterogeneity and anisotropy in rat hippocampus.
AB  - We provide evidence for anisotropic diffusion in rat corpus callosum and
      hippocampus. The preferential diffusion pathway in corpus callosum is along the
      myelinated axon fibres; in the hippocampus diffusion is easier along the
      transversal axis (x) than along the sagittal (y) or vertical (z) axes. In all
      areas studied, i.e. in the cortex, corpus callosum and hippocampus, the mean ECS
      volume fraction alpha (alpha = ECS volume/total tissue volume) ranged between
      0.20 and 0.22 and mean non-specific uptake k' was between 4.0 and 5.9 x 10(-3) s
      1. Diffusional anisotropy in the hippocampus may be of importance for
      extrasynaptic transmission and in the 'cross-talk' between synapses.

PMID- 9631419
TI  - Localization of Ca-ATPase in frog crista ampullaris.
AB  - The distribution of Ca-ATPase in frog crista ampullaris was mapped
      ultracytochemically by using a one-step lead citrate reaction. Electron-dense
      precipitates, as an expression of Ca-ATPase activity, were observed on the
      surface of stereocilia and on the apical membrane surrounding the cuticular plate
      of hair cells. Sensory cells of the isthmus region showed more reactivity than
      those of the peripheral regions of the crista. No reaction products were
      detectable on the basolateral membranes and in cytoplasmatic organelles.
      Supporting cells of the crista showed a quite variable Ca-ATPase reaction on
      microvilli and on basolateral membranes. The presence of an evident reactivity on
      the stereocilia is consistent with the existence of an apical calcium microdomain
      involved in the mechano-transduction process and supports the current view that
      calcium ions enter the stereocilia during natural stimulation. On the other hand,
      the lack of an observable reactivity on the basolateral membrane of hair cells
      suggests that in semicircular canals other mechanisms of active transport of
      calcium ions across the plasma membrane, such as Na-Ca exchange, may be involved
      in homeostasis of the ion.

PMID- 9631418
TI  - Low activity allele of catechol-o-methyltransferase gene and Japanese unipolar
      depression.
AB  - Several studies have shown that depressed patients have significantly lower
      catechol-o-methyltransferase (COMT) activity than healthy controls. Two COMT
      genes coding for low activity, COMTL, and high activity, COMTH have been
      identified. We undertook an association study on 75 depressive disorder patients,
      40 bipolar disorder patients and 135 healthy controls. All the subjects were
      Japanese. Patients with depressive disorders exhibited a significantly higher
      rate of genotypes with the COMTL allele than healthy controls (p = 0.012), which
      was not the case in patients with bipolar disorders. The presence of the COMTL
      allele was significantly associated with depressive disorders (odds ratio 2.19,
      95% CI 1.19-4.03). Our results suggest the COMTL allele contributed to the
      etiologies of depressive disorders.

PMID- 9631420
TI  - MK-801 does not enhance dopaminergic cell survival in embryonic nigral grafts.
AB  - Two groups of hemiparkinsonian rats received grafts of embryonic ventral
      mesencephalon with or without the addition of the NMDA receptor antagonist
      (+)dizocilpine hydrogen maleate (MK-801). When added to the cell suspension, a 10
      microM concentration of MK-801 did not enhance the survival of tyrosine
      hydroxylase positive neurones in the grafts. These findings suggest that cell
      death occurring during nigral transplantation is not primarily due to
      excitotoxicity.

PMID- 9631421
TI  - Differences in the cerebrovascular anatomy of C57black/6 and SV129 mice.
AB  - The vascular architecture of the brain of C57Black/6 and SV129 mice was studied
      following microvascular injection of carbon black stained latex. The dorsal brain
      surface was photographed to determine the number, diameter, and position of pial
      anastomotic vessels between the middle and anterior cerebral arteries. The mean
      number and diameter of anastomoses were not significantly different, but the line
      of anastomoses interconnecting the half way points of anastomotic vessels was
      located significantly closer to the midline in C57Black/6 mice, demonstrating
      that the middle cerebral artery had a larger vascular supplying territory than in
      SV129 mice. This explains the larger infarct volume previously reported in
      C57Black/6 mice, and raises concerns about the use of C57Black/6 and SV129 mice
      as parent strains for genetically modified animals in stroke research.

PMID- 9631422
TI  - Influence of stimulus speed upon the antagonistic surrounds of area MT/V5
      neurons.
AB  - We investigated the effect of stimulus speed upon surround antagonism in macaque
      MT/V5 neurons, using probe stimuli placed at different positions in the surround.
      Their speed was varied, while the stimulation of the excitatory receptive field
      (RF) was held at optimal speed. Most Surrounds proved asymmetric, arising from a
      single region on one side of RF, although bilaterally and circularly symmetric
      surrounds were occasionally observed. Surround organization was generally
      retained at faster or slower surround speeds. Speed-dependent changes usually
      entailed diminished position dependence of surround influence, consequent to
      reduced surround effect at the position producing maximum inhibition. The effect
      of a stimulus covering the entire surround was much less dependent upon motion
      speed. Results show that surround non-uniformity is a robust finding in MT/V5 and
      endows neurons with multiple mechanisms for extracting surface orientation in
      depth.

PMID- 9631423
TI  - Microdialysis and EEG in rats reveal cortical PGE2 changes during sleep and
      wakefulness.
AB  - Prostaglandin (PG) E2 production was assessed in freely moving rats using the
      technique of microdialysis in the prefrontal cortex associated with parallel
      cortical EEG recordings. PGE2 concentrations were 40% higher during wakefulness
      than during slow wave sleep. PGE2 values varied during wakefulness with a maximal
      increase in the middle of the stage and a drop towards lower values before the
      occurrence of slow wave sleep. These variations were similar to those observed
      previously in the rostromedial hypothalamus, where PGE2 concentration was 2.6
      times lower than that in the cortex. These data document a positive correlation
      between cortical EEG activation and PGE2 levels. Taken together with
      pharmacological data on the awakening effect of centrally administered PGE2,
      these observations are in favor of an involvement of PGE2 in the generation of
      wakefulness.

PMID- 9631424
TI  - Asymmetry of the interhemispheric visuomotor integration in callosal agenesis.
AB  - We measured visuomotor responses following the Poffenberger paradigm in an
      acallosal boy, without other detectable neural defects. In this task crossed and
      uncrossed RT reflect the time of intra- and interhemispheric integration and the
      difference (CUD) estimates the interhemispheric transfer time. CUDs in the
      hemifields were largely asymmetrical in this subject, suggesting that visuomotor
      processing is extremely lengthened when the right hemisphere (RH) detects the
      light and the left hemisphere (LH) controls the motor output whereas it is very
      fast in the opposite direction. This asymmetry, which is present in comparable
      data available from the literature, may indicate the functional superiority of
      the LH in controlling the ipsilateral hand, as suggested by recent MRI findings.

PMID- 9631425
TI  - The immune modulator Linomide prevents neuronal death in injured peripheral
      nerves of the mouse.
AB  - Neuronal death after injury or disease could result from imbalanced cytokine
      expression. Linomide (LS-2616, quinoline-3-carboxamide), a synthetic
      immunomodulator with effects on cytokine production, suppresses autoimmune
      diseases of the nervous system. Here adult mice were pre-treated with 200
      mg/kg/day of Linomide for 9 days, after which the sciatic nerves were crushed.
      After another 10 days of Linomide treatment the dorsal root ganglia were
      dissected out and stained for apoptosis, either immediately or after 2 days in
      culture, which increases cell death. Superior cervical ganglia were also cultured
      for 2 days. The Linomide pretreatment profoundly reduced (approximately 60-80%)
      the injury-induced apoptotic death of neurons and satellite cells in both
      systems. The results suggest that modulation of the inflammatory cytokine cascade
      is a promising road to nerve cell rescue.

PMID- 9631426
TI  - Modulation by GABA transmission in the substantia nigra compacta and reticulata
      of locomotor activity in rats exposed to high pressure.
AB  - Helium pressure of > 20 bar causes neuroexcitatory changes referred to as the
      high pressure neurological syndrome. In rodents, symptoms include locomotor and
      motor activity (LMA), myoclonia and, at greater pressure, convulsions. We studied
      the effects of the GABA reuptake inhibitor nipecotic acid, the GABA transaminase
      inhibitor gamma-vinyl-GABA (GVG), the GABAA receptor agonist muscimol, and the
      GABAB receptor agonist baclofen. Whatever the drug used, bilateral administration
      in the substantia nigra reticulata (SNR) or in the substantia nigra compacta
      (SNC) showed no significant effects on myoclonia. In contrast, administration in
      the SNR of nipecotic acid, GVG, and baclofen resulted in a significant decrease
      of LMA; administration of muscimol in the SNR increased LMA. No significant
      effect was seen when drugs were injected in the SNC. These results suggest that
      changes in GABA transmission in the SNR, but not in the SNC, play a crucial role
      in the control of motor activity and the regulation of movement.

PMID- 9631427
TI  - A novel substance associated with gallamine-induced myoclonus.
AB  - If gallamine or d-tubocurarine gains access to the central nervous system it
      produces a myoclonus, a synchronized jerking of many skeletal muscles. Each jerk
      is accompanied by a slow wave in the inferior olive. The jerking continues for 24
      h or more after the gallamine or d-tubocurarine can no longer be detected in the
      CSF. We report here that a novel substance appears in the CSF and persists for a
      long period of time, possibly as long as the twitching. This substance is not
      corticotrophin-releasing factor (CRF) nor does CRF or harmaline (a substance
      causing a tremor by an action on the inferior olive) lead to the appearance of
      the novel substance. At present the nature of this substance is not known.

PMID- 9631428
TI  - Seizures in rats treated with kainic acid induce Fos-like immunoreactivity in
      locus coeruleus.
AB  - Kainic acid-triggered seizures (KATS) induce Fos-like immunoreactivity (FLI) in
      limbic structures, which send efferents to the locus coeruleus (LC). Following
      KATS, brain stem sections were stained for Fos immunocytochemistry and double
      immunostained for Fos and dopamine beta-hydroxylase (DBH). KA-treated animals
      showed significantly greater numbers of FLI neurons in the LC than control
      animals (p < 0.05). Co-localization of DBH/Fos was observed in 89.7% of the LC
      neurons in KA-treated animals and in 1.4% of LC neurons in control animals. Thus,
      KATS heavily induce Fos in DBH-containing neurons in the LC, which are known to
      project to the hippocampus. However, the role of activation of the LC
      noradrenergic neurons during KATS is not well understood at this present time.

PMID- 9631429
TI  - The effects of repeated alcohol exposure on the neurochemistry of the
      periadolescent nucleus accumbens septi.
AB  - Substance abuse is a major issue in today's society and is an issue of critical
      importance in the adolescent population. Research indicates that substance use is
      often initiated during the adolescent period and that brain reward areas are
      still undergoing changes during this time. Despite this, little research has
      investigated the effects of repeated drug use on the reward mechanisms of
      periadolescent animals. For this reason, the present study examined the effects
      of repeated ethanol (EtOH) administration on the responsiveness of the nucleus
      accumbens septi (NAcc) to either EtOH or saline challenge. The data indicate that
      repeated exposure to EtOH produces temporal shifts in the dopaminergic (DAergic)
      activity of the NAcc, with peak activity occurring earlier. Importantly,
      following repeated injections of EtOH, saline injections alone elicit DA
      increases in the NAcc suggesting that the context of alcohol administration
      produces fundamental changes in the way that neurochemical reinforcement
      mechanisms respond. The expectancy of the drug alone elicits reward-related
      activity within the NAcc.

PMID- 9631430
TI  - Induction of NG108-15 cells differentiation by human bone marrow stromal cells.
AB  - The survival and differentiation of neuronal cells is dependent on factors such
      as neurotrophins, cytokines and components of extracellular matrix. Bone marrow
      stromal cells have been shown to support the growth and differentiation of
      neuroblastoma cells. In an attempt to study the effects of bone marrow stromal
      cells on neuronal differentiation, we have co-cultured neuroblastoma x glioma
      hybrid NG108-15 cells with human bone marrow stromal cells. After co-culturing,
      clones exhibiting morphological differentiated phenotype and high level of
      neurofilament expression were isolated. Interestingly, these clones maintain
      their ability to proliferate in contrast to differentiated NG108-15 cells induced
      by dibutyryladenosine 3',5'-cyclic monophosphate. These results suggested that
      bone marrow stromal cells can induce partial differentiation of NG108-15 cells.

PMID- 9631431
TI  - Phoneutria nigriventer toxins block tityustoxin-induced calcium influx in
      synaptosomes.
AB  - Neurotoxins can help the understanding of mechanisms involved in
      neurotransmission. We here report that two neurotoxin isoforms, Tx3-3 and Tx3-4
      obtained from the venom of the spider Phoneutria nigriventer inhibited the 45Ca2+
      influx in rat cortical synaptosomes induced by the scorpion venom tityustoxin.
      The IC50 for Tx3-3 and Tx3-4 were 0.32 and 7.9 nM, respectively. The neurotoxins
      Tx3-3 and Tx3-4 are very effective in inhibiting 45Ca2+ influx and they should be
      useful in studies involving Ca(2+)-dependent processes.

PMID- 9631432
TI  - TNF alpha induces a protein kinase C-dependent reduction in astroglial K+
      conductance.
AB  - Incubation of cultured cortical astrocytes with tumor necrosis factor alpha (TNF
      alpha) led to a marked reduction of membrane potential. Here we report that this
      depolarization depends on activation of protein kinase C (PKC), since it could be
      blocked by the PKC antagonists staurosporine and H7 and it could be mimicked by
      direct activation of PKC using the phorbol ester phorbol 12-myristate 13 acetate
      (PMA). Analyses of whole cell currents revealed a reduction of inwardly
      rectifying K+ currents whereas K+ outward currents were not affected. We conclude
      that TNF alpha induces changes of basic electrophysiological properties of
      astrocytes which are similar to those induced by proliferation or an in vitro
      model of traumatic injury.

PMID- 9631433
TI  - Abnormalities of Wnt signalling in schizophrenia--evidence for neurodevelopmental
      abnormality.
AB  - The Wnt signalling pathway is central to normal brain development in vertebrates
      and invertebrates and mediates cell fate determination, cell adhesion and cell
      proliferation. However, its relevance to disorders of cerebral development in man
      is untested. We evaluated the potential involvement of the Wnt signalling pathway
      in schizophrenia, a disorder of neurodevelopment origin in which alterations in
      neuronal lamination and orientation have been described. Using
      immunohistochemistry and semi-quantitative rating scales, we examined the
      distribution of two components of the Wnt signalling pathway, beta-catenin and
      gamma-catenin in the hippocampus and subiculum of 12 schizophrenic (DSMIIR
      criteria) and 14 control subjects. Both catenins were distributed as
      intraneuronal diffuse and/or ring shaped forms. The diffuse staining of both
      forms catenin were reduced in the CA3 and beta-catenin was also reduced in the
      CA4 hippocampal subregion among schizophrenic subjects. These alternations may
      represent the basis of the developmental brain abnormalities found in
      schizophrenia and would have functionally important consequences in the adult.

PMID- 9631434
TI  - (-)-Nicotine increases mRNA encoding G3PDH and the vesicular acetylcholine
      transporter in vivo.
AB  - The effects of acute in vivo (-)-nicotine exposure on neuronal expression of mRNA
      encoding the vesicular acetylcholine transport (VAChT) and the glycolytic enzyme
      glyceraldehyde-3-phosphate dehydrogenase (G3PDH) were examined. The reverse
      transcription polymerase chain reaction was used to amplify cDNA derived from
      brain tissue of adult male rats injected acutely with (-)-nicotine and semi
      quantification of cDNA products conducted using anion exchange chromatography. In
      cerebral cortex, levels of cDNA derived from the VAChT mRNA were increased by >
      65% above control levels 1 h after (-)-nicotine (0.8 mg/kg, s.c.) exposure. In
      hippocampal samples, levels of this cDNA were increased by 15% above control
      levels. cDNA derived from G3PDH mRNA was increased by 86% and 280% above control
      levels in the cerebral cortex and hippocampus, respectively. Thus, increased
      expression and function of proteins associated with these mRNA species are likely
      consequences of acute (-)-nicotine exposure.

PMID- 9631435
TI  - Phosmet induces up-regulation of surface levels of the cellular prion protein.
AB  - Chronic (2 day) exposure of human neuroblastoma cells to the organophosphate
      pesticide phosmet induced a marked concentration-dependent increase in the levels
      of PrP present on the cell surface as assessed by biotin labelling and
      immunoprecipitation. Levels of both phospholipase C (PIPLC)-releasable and non
      releasable forms of PrP were increased on the plasma membrane. These increases
      appear to be due to post-transcriptional mechanisms, since PrP mRNA levels as
      assessed by Northern blotting were unaffected by phosmet treatment. These data
      raise the possibility that phosmet exposure could increase the susceptibility to
      the prion agent by altering the levels of accessible PrP.

PMID- 9631436
TI  - Receptor-coupled phospholipase C and adenylyl cyclase function with different
      calcium pools in astrocytes.
AB  - Astrocytes express phospholipase C (PLC)-coupled metabotropic glutamate receptors
      (only mGluR5 is detectable) and adenylyl cyclase (AC)-linked beta-adrenergic
      receptors. Calcium-sensitive effector enzymes are associated with these signal
      transduction pathways, but the relevant calcium compartments involved were found
      to be different. mGluR5-linked PLC responded primarily to extracellular Ca2+,
      suggesting a close spatial relation between the enzyme and Ca2+ entry channels.
      On the other hand, the calcium-inhibited AC associated with beta-adrenergic
      receptors was sensitive to intracellular Ca2+ selectively accessible to
      intracellular Ca2+ chelation. Furthermore, cAMP formation induced by direct
      activation of AC by forskolin was less responsive to intracellular Ca2+ chelation
      than that evoked by the receptor-activated AC, raising the possibility of
      selective access of the receptor to a pool of calcium-inhibited AC and/or the
      calcium modulation of some components of the coupling pathway.

PMID- 9631438
TI  - Muscarinic toxin selective for m4 receptors impairs memory in the rat.
AB  - The selectivity of the muscarinic toxin MT3 from green mamba snake venom was
      corroborated by inhibition of the binding of [3H]NMS, a classical muscarinic
      radioligand, to native and cloned muscarinic receptors, showing 214-fold higher
      affinity for m4 than for m1 subtype, without significant binding to the others.
      The highest concentrations of MT3 sites (putative m4 receptors) in the rat brain
      were found in striatum and olfactory tubercle, intermediate concentration in
      dentate gyrus and CA1, and lower but still conspicuous levels in CA3 and frontal
      cortex. MT3 caused retrograde amnesia of an inhibitory avoidance task, when
      injected into the dorsal hippocampus of rats after training, suggesting a
      positive role of these MT3 sensitive sites, which are probably m4 muscarinic
      receptors, in memory consolidation of this task.

PMID- 9631439
TI  - Diversity of single potassium channels in isolated snail neurons.
AB  - Comparison of K+ channels in mollusk and mammalian neurons has been made to
      elucidate their fundamental properties. Using patch clamp cell-attached
      configuration, K+ channels in isolated snail neurons were separated into three
      subtypes: with big (BKC), medium (MKC) and small (SKC) unitary conductances. BKC
      and MKC were activated at -30 mV and SKC at more negative potentials. BKC and MKC
      proved sensitive to TEA, whereas SKC were sensitive to 4-AP. Cd2+ in the pipet
      decreased unitary conductance of BKC by 55% and of MKC by about 31%. Bath
      application of 5-HT selectively suppressed MKC. It is suggested that BKC can be
      referred to large conductance Ca(2+)-dependent K+ currents (KCa), MKC to
      intermediate conductance KCa and SKC channels comply with the characteristics of
      A current of mammals. These data show that KCa and A currents may be the most
      general types of currents generated by K+ channels.

PMID- 9631437
TI  - Primary structure of GAP-43 mRNA expressed in the spinal cord of ALS patients.
AB  - Recent evidence suggests that the growth associated protein GAP-43 is involved in
      the pathology of amyotrophic lateral sclerosis (ALS). In order to assess the
      primary structure of the GAP-43 mRNA expressed in the spinal cord of ALS
      patients, the total coding region of the GAP-43 mRNA was amplified from
      postmortem human spinal cord specimens using the reverse transcriptase-polymerase
      chain reaction (RT-PCR) method. GAP-43 amplification products were clearly
      detected in all of the ALS cases but not in the normal controls. The GAP-43 mRNA
      and the deduced amino acid sequences from all ALS cases coincided completely with
      the sequence of human fetal GAP-43. These results suggest that the abnormal
      expression of GAP-43 mRNA underlying the pathogenesis of ALS is due to a
      quantitative increase, and that there are no qualitative abnormalities associated
      with a change in the amino acid sequences.

PMID- 9631440
TI  - The effects of graded hypoxia on intraparenchymal arterioles in rat brain slices.
AB  - Hypoxia-induced changes in intracerebral arterioles, the major determinants of
      local cerebral oxygen delivery, are not well understood. Hippocampal arteriolar
      diameters were measured in rat brain slices using computerized videomicroscopy.
      In group 1 (control), artificial cerebrospinal fluid oxygen tension (PO2) was
      maintained at 500 mmHg. In groups 2 and 3, PO2 was gradually reduced to anoxia
      (95% N2/5% CO2). In group 3, prostaglandin F2a alpha was given to approximate
      physiological myogenic tone. PCO2 and pH were controlled. Graded hypoxia
      progressively dilated vessels (PO2 300 mmHg = 2.4 +/- 1.2%, 4.2 +/- 1.6%; PO2 90
      mmHg = 15.4 +/- 3.0%, 14.5 +/- 1.8%; groups 2 and 3, respectively). The presence
      of preconstriction did not influence the extent of hypoxia-induced dilation. This
      vasorelaxation may be important in maintaining cerebral oxygen delivery during
      microvascular hypoxia.

PMID- 9631441
TI  - Microglial expression of the prion protein.
AB  - The prion protein (PrPc) is a normal cellular protein expressed by neurones and
      astrocytes. An altered isoform, PrPSc is thought to transmit spongiform
      encephalopathies. Here we show that microglia also express PrPc. Sensitivity of
      microglia to activation is enhanced by increased expression of PrPc. Bacterial
      endotoxin increases superoxide production and inhibits profileration of microglia
      more effectively when microglia express PrPc. PrPc expression is therefore
      important for the normal function of microglia.

PMID- 9631442
TI  - Reduced kynurenine aminotransferase-I activity in SHR rats may be due to lack of
      KAT-Ib activity.
AB  - Kynurenine aminotransferase I (KAT-I), which also shows glutamine transaminase K
      (GTK) activity, catalyses the conversion of kynurenine to kynurenic acid, an
      endogenous glutamate antagonist. Both the GTK and KAT enzyme activities were
      found to be significantly reduced in kidney, brain and medulla oblongata
      homogenates of spontaneously hypertensive (SHR) compared to Wistar-Kyoto (WKY)
      rats. Enzyme activity stains on native gel separations of partially purified
      kidney homogenates was associated with two major bands of GTK (KAT-I)-activity in
      WKY and Wistar rats, KAT-Ia and KAT-Ib. SHR rats however showed only KAT-Ia
      activity. These findings suggest that the absence of KAT-Ib activity may result
      in a reduced ability to synthesise kynurenic acid in SHR rats, this may help to
      explain the enhanced sensitivity to glutamate seen in this strain.

PMID- 9631443
TI  - CEP-1347/KT7515, a JNK pathway inhibitor, supports the in vitro survival of chick
      embryonic neurons.
AB  - Developing neurons depend on target-derived trophic factors for survival in vivo
      and in vitro, which also decrease the activity of c-Jun N-terminal kinase (JNK).
      We have recently described a survival-promoting effect of inhibitors of cyclin
      dependent kinases and JNK on chick peripheral embryonic neurons. Here, we report
      that the small trophic molecule CEP-1347/KT7515, which has been shown to inhibit
      the JNK signalling pathway, can promote long term-survival of cultured chick
      embryonic dorsal root ganglion, sympathetic, ciliary and motor neurons. Because
      of their pharmacological properties, small trophic molecules such as CEP
      1347/KT7515 might be of interest for the treatment of neurodegenerative
      disorders.

PMID- 9631444
TI  - Intracisternal osteogenic protein-1 enhances functional recovery following focal
      stroke.
AB  - Osteogenic protein-1 (OP-1, BMP-7) is a member of the transforming growth factor
      beta (TGF-beta) superfamily that selectively induces dendritic outgrowth from
      cultured neurons. We injected human recombinant OP-1 (1 or 10 micrograms) or
      vehicle into the cisterna magna of mature male Sprague-Dawley rats 1 and 4 days
      after focal cerebral infarction induced by middle cerebral artery (MCA)
      occlusion. OP-1 treatment was associated with a marked enhancement of recovery of
      sensorimotor function of the impaired forelimb and hindlimb (contralateral to
      infarcts) as assessed by limb placing tests. This effect appeared to be dose
      dependent. There was no difference in infarct volume between OP-1 and vehicle
      treated rats. The mechanisms of enhanced recovery by intracisternal OP-1 may
      include promotion of dendritic sprouting in the intact uninjured brain.

PMID- 9631445
TI  - Hypoxic and hypoglycaemic changes of intracellular pH in cerebral cortical
      pyramidal neurones.
AB  - Intracellular pH and membrane potential were measured during hypoxia and/or
      hypoglycaemia in cortical pyramidal neurones of a rat cortical slice preparation.
      Intracellular pH (pHi) was calculated from ratiometric microfluorometry of the pH
      sensitive dye BCECF injected via sharp recording microelectrodes into the
      neurones. Transient (5 min) hypoxia induced a fall of pHi (7.12 +/- 0.03) of 
      0.72 +/- 0.11 pH units while transient (10 min) hypoglycaemia induced an increase
      of 0.37 +/- 0.09 pH units. Hypoglycaemia did not prevent the hypoxic
      acidification. Lowering extracellular Na+ induced a membrane hyperpolarization
      and alkalinization by 0.29 +/- 0.12 pH units but did not affect the development
      or recovery of the hypoxic acidification. The alkalinization during hypoglycaemia
      suggested that there is some anaerobic glycolysis under normoglycemic conditions.
      The hypoxic acidification, however, is unlikely to result from anaerobic
      glycolysis or reversal of Na(+)-dependent H+ extrusion.

PMID- 9631446
TI  - Increased expression of the TIAR protein in the hippocampus of Alzheimer
      patients.
AB  - T-cell restricted intracellular antigen related protein (TIAR) is an RNA-binding
      protein that is supposed to be involved in the process of stress-induced
      apoptosis. TIAR triggers DNA fragmentation in permeabilized thymocytes and its
      expression diminishes in the cell nucleus and rises simultaneously in the
      cytoplasm during Fas-induced cell death. Using a monoclonal antibody against
      TIAR, we stained different areas of the hippocampus from seven controls and 14
      patients with Alzheimer's disease (AD). There was a clear expression of TIAR in
      the hippocampus of non-demented controls. Surprisingly, a significant increase
      was found in the expression of TIAR in the hippocampal area in AD. The increased
      expression of TIAR in AD may be related to the process of neurodegeneration in
      the hippocampus.

PMID- 9631447
TI  - Rapid increase of NGF, BDNF and NT-3 mRNAs in inflamed bladder.
AB  - Nerve growth factor (NGF) is a mediator of hyperalgesia and has been previously
      associated with sensory and reflex changes after inflammation of the urinary
      bladder. A sensitive assay was developed to examine neurotrophin gene expression
      after bladder inflammation by turpentine, which causes a short-lived inflammatory
      response. Two hours, but not 6 or 24 h after induction of inflammation, there
      were significant increases in levels of NGF, brain-derived neurotrophic factor
      and neurotrophin-3 mRNAs. NGF immunoreactivity was elevated with a similar time
      course to its mRNA. Our results suggest that during bladder inflammation,
      endogenous NGF is rapidly up-regulated and released to mediating sensory and
      reflex changes. Brain-derived neurotrophic factor and neurotrophin-3 may also
      have a role in the inflammatory response.

PMID- 9631448
TI  - Differences in the kappa opioid receptor mRNA content in distinct brain regions
      of two inbred mice strains.
AB  - The inbred C57BL/6 mouse strain is known to prefer an ethanol solution in a two
      bottle choice procedure, whereas the inbred DBA/2 mouse strain avoids drinking
      ethanol in this paradigm. The genetic basis of this behavior is still unclear but
      the endogenous opioid system is one of the factors thought to be involved.
      Therefore, we were interested to see if there are basal differences between the
      two lines of mice in the kappa opioid receptor (kappa OR) mRNA content in
      different brain regions. Because of the low expression level of this gene and the
      limited amount of tissue we developed a sensitive competitive reverse
      transcription-polymerase chain reaction (RT-PCR) assay for evaluation of levels
      of kappa OR mRNA in brain tissue. In septum and hypothalamus the DBA/2 mice
      showed a significantly higher basal level of kappa OR mRNA than did C57BL/6 mice.
      It is suggested that a difference in basal amount of kappa OR mRNA among these
      strains could lead to differences in kappa OR activity and subsequently to
      variations between the strains in distinct behaviors such as in ethanol
      preference.

PMID- 9631449
TI  - Glucocorticoids alter recovery processes in the rat retina.
AB  - The effect of glucocorticoids on the electroretinogram (ERG) b-wave was studied
      in freely moving rats. b-Waves were evoked by flashes delivered by a light
      emitting diode implanted under the skin above the left eye. I.v. corticosterone
      and dexamethasone injection induced a transient increase in b-wave amplitude at
      90 min. Retinal oscillatory potentials (OPs) were similarly enhanced.
      Pretreatment with a glucocorticoid receptor antagonist (RU 38486) abolished both
      increases. These results suggest that enhancements in retinal potentials may be
      the result of a glucocorticoid-induced facilitation of the processes under way in
      normal Muller cells following retinal excitation.

PMID- 9631450
TI  - Vestibular memory-contingent saccades involve somatosensory input from the body
      support.
AB  - Humans use vestibular head-in-space information when redirecting gaze towards
      remembered target location in space. This study shows that neck input is also
      involved. Normal subjects performed saccades towards remembered locations in
      space of a previously seen target following passive horizontal rotations of the
      head or trunk. Saccades based on vestibular input alone fell short at low
      stimulus frequencies. Addition of neck input modified the responses, making them
      more accurate when the head was rotated on the stationary trunk. The results
      support a concept according to which vestibular input is channeled via
      proprioceptive coordinate transformations through the haptically perceived body
      support before yielding a sense of head motion in space. The loop is also
      involved in the saccadic gaze mechanism.

PMID- 9631451
TI  - Evidence for an endogenous clock in the retina of rainbow trout: II. Circadian
      rhythmicity of serotonin metabolism.
AB  - The purpose of the present study was to investigate patterns of circadian
      rhythmicity in the retina of a salmonid fish, the rainbow trout (Oncorhynchus
      mykiss). Our data present the first demonstration of intraretinal variations of
      serotonergic substances under light/dark-conditions (LD) and during continuous
      darkness (DD). All substances examined (serotonin, N-acetyl serotonin, 5
      hydroxytryptophol, 5-hydroxyindole acetic acid) were rhythmic in LD. Serotonin, N
      acetyl-serotonin, and 5-hydroxyindole acetic acid showed a preservation of
      specific features of rhythmicity in DD indicating the involvement of an
      endogenous pacemaker in the regulation of serotonin metabolism in the rainbow
      trout eye.

PMID- 9631452
TI  - Caspase-mediated cleavage is not required for the activity of presenilins in
      amyloidogenesis and NOTCH signaling.
AB  - The Alzheimer's disease (AD) associated presenilin (PS) proteins are
      proteolytically processed. One of the processing pathways involves cleavage by
      caspases. Pharmacological inhibition of caspases is currently being discussed as
      a treatment for a variety of neurodegenerative diseases, including AD. We
      therefore inhibited caspase mediated processing of PS-1 and PS-2 in cells
      transfected with wt and mutant PS by mutagenizing the substrate recognition site
      or by using specific peptide aldehydes known to block caspases. We found that the
      inhibition of caspase mediated processing of PS proteins does not decrease its
      amyloidogenic activity. PS cDNA constructs with mutations in the caspase cleavage
      site are biologically active in Caenorhabditis elegans such as the wt human PS
      proteins, demonstrating that caspase-mediated cleavage is not required for the
      physiological PS function in NOTCH signaling.

PMID- 9631453
TI  - IFN-gamma production of adult rat astrocytes triggered by TNF-alpha.
AB  - IFN-gamma plays an important role in modulating inflammatory responses within the
      CNS. The cell type responsible for IFN-gamma production within the CNS is less
      well defined. We examined the production and regulation of IFN-gamma by adult rat
      astrocytes. IFN-gamma was hardly detectable in cultured astrocytes, while
      addition of TNF-alpha dose-dependently induced IFN-gamma production by
      astrocytes. No IFN-gamma production by astrocytes could be induced by LPS, IL-10
      or TGF-beta 1. TNF-alpha-induced IFN-gamma production by astrocytes was inhibited
      by treatment of astrocytes with TGF-beta 1, but not IL-10. TNF-alpha induced IFN
      gamma production by astrocytes was confirmed by using immunocytochemical
      staining. The data suggest that astrocyte-derived IFN-gamma induced by TNF-alpha
      may participate in local immune reactions of the brain in an autocrine and
      paracrine fashion.

PMID- 9631454
TI  - Mannan-binding lectin in human serum, cerebrospinal fluid and brain tissue and
      its role in Alzheimer's disease.
AB  - Mannan-Binding lectin (MBL) is a serum lectin which can activate the classical
      complement pathway. Complement proteins of the classical pathway have been found
      in the brains of patients with Alzheimer's disease (AD) in association with AD
      brain pathology. To investigate the role for MBL in AD we have looked for its
      presence in the brain by immunohistochemistry and determined the levels of MBL in
      paired samples of cerebrospinal fluid and serum from AD patients and controls.
      MBL was detected in association with blood vessels in the brain tissue of both AD
      patients and control subjects. There was no apparent difference in the
      distribution of MBL in the brain tissue between the two groups. The mean
      concentration of MBL in the CSF was 44% lower in AD patients than in controls (AD
      154 +/- 35 pg/ml, n = 19; non-AD 276 +/- 50 pg/ml, n = 15, p < 0.05). The levels
      of MBL in serum were not significantly different in the two groups. Thus, this
      study shows that MBL is associated with blood vessels in the brains of both AD
      and control subjects. Moreover, CSF levels of MBL appear to be lower in AD
      patients than in control subjects which may indicate a higher degree of MBL
      consumption connected with complement activation in the AD patients.

PMID- 9631455
TI  - Neuromagnetic fields preceding unilateral movements in dextrals and sinistrals.
AB  - Movement-related magnetic fields were recorded with a whole-head
      magnetoencephalographic system in three dextrals and three sinistrals during
      right or left index finger extension. The motor field (MF) demonstrated an
      asymmetrical isofield map pattern with larger field reversal over the
      contralateral hemisphere for dominant hand movement and an almost symmetrical
      pattern for non-dominant hand movement in each subject. The equivalent current
      dipole moment of the MF for the contralateral hemisphere was significantly larger
      than the ipsilateral hemisphere for dominant hand movement, and almost equal for
      both hemispheres for non-dominant hand movement. These results were congruent for
      both dextrals and sinistrals, suggesting a more important role of the hemisphere
      contralateral to the dominant hand in unilateral voluntary movement, regardless
      of handedness.

PMID- 9631456
TI  - Reactive astrocytes express nitric oxide synthase in the spinal cord of
      transgenic mice expressing a human Cu/Zn SOD mutation.
AB  - The distribution of the neuronal isoform of nitric oxide synthase (nNOS) in the
      spinal cord of transgenic mice expressing a mutated human copper/zinc superoxide
      dismutase gene was enhanced when investigated by immunocytochemistry.
      Immunocytochemistry showed intensely stained NOS-immunoreactive (IR) glial cells
      with the appearance of astrocytes in the spinal cord and brain stem of transgenic
      mice, but none were observed at these sites in control mice. Using antisera
      directed against GFAP, the specific marker for astrocyte, the glial cells were
      confirmed by immunocytochemistry to be astrocytes. This immunocytochemical
      evidence suggests that nitric oxide may mediate glutamate neurotoxicity, and this
      study provides the first in vivo evidence that nitric oxide may be implicated in
      the pathologic process of human familial amyotrophic lateral sclerosis.

PMID- 9631457
TI  - Hippocampal atrophy is related to impaired memory, but not frontal functions in
      non-demented Parkinson's disease patients.
AB  - We investigated the neuropsychological correlates of hippocampal atrophy in
      Parkinson's disease (PD) patients. The memory impaired PD patients had smaller
      hippocampi than other PD patients. The performance of PD patients in spatial
      working memory and attentional set-shifting correlated with the severity of motor
      defect, and not with hippocampal atrophy. Our results suggests that failure of
      verbal/visual memory may be related to hippocampal atrophy in Parkinson's
      disease. On the contrast, the defect in spatial working memory and attentional
      set-shifting may be sensitive to dysfunction of 'fronto-striatal' systems in PD
      patients.

PMID- 9631458
TI  - Neurogenic oedema and vasodilatation: effect of a selective neuronal NO
      inhibitor.
AB  - The effects of a neuronal nitric oxide synthase (nNOS) inhibitor, 1-(2
      trifluoromethylphenyl)imidazole (TRIM) on rat sensory saphenous nerve-induced
      neurogenic inflammation were investigated. TRIM (50 mg kg-1, i.p.), but not 2
      trifluoromethylphenol (TRIMPOH) which lacks nNOS inhibitory activity, inhibited
      neurogenic oedema by 55.8 +/- 6.5% (n = 6, p < 0.05). The effect of TRIM was
      partially reversed by L-arginine (100 mg kg-1, i.v., p < 0.01). TRIM also caused
      a reduction (p < 0.05) in neurogenic vasodilatation but had no effect on
      neuropeptide responses induced by substance P + CGRP. Topically applied TRIM (100
      microliters of 150-250 mg ml-1) inhibited neurogenic oedema (p < 0.01). Thus, use
      of this recently described nNOS inhibitor has provided new evidence to further
      the hypothesis that nNOS plays a role in modulating sensory nerve-mediated
      neurogenic inflammation.

PMID- 9631459
TI  - Tacrine and donepezil attenuate the neurotoxic effect of A beta(25-35) in rat
      PC12 cells.
AB  - The effect of the cholinesterase inhibitors tacrine and donepezil on A beta(25
      35)-induced toxicity was investigated in rat pheochromocytoma PC12 cells by
      measuring the mitochondrial activity. Tacrine and donepezil was found in clinical
      relevant concentrations (10(-7)-10(-6) M) to attenuate A beta(25-35)-induced
      toxicity in PC12 cells. The neuroprotective effect of tacrine was blocked in the
      presence of the nicotinic antagonists mecamylamine (10(-5) M) and tubocurarine
      (10(-5) M), suggesting an interaction via nicotinic receptors. This study
      demonstrates that tacrine and donepezil can exert neuroprotective properties
      which might be of importance and contribute to the clinical efficacy of
      cholinesterase inhibitors in the treatment of Alzheimer's disease.

PMID- 9631460
TI  - Persistence of somatic and dendritic growth associated processes and induction of
      dendritic sprouting in motoneurones after neonatal axotomy in the rat.
AB  - The effect of neonatal axotomy on the maturation of motoneurone somadendritic
      morphology was studied in identified motoneurones innervating the ankle
      dorsiflexor muscles tibialis anterior (TA) and extensor digitorum longus (EDL) of
      the rat by intracellular injection of Lucifer Yellow and confocal microscopy. At
      birth, the entire somatodendritic surface is covered with fine filopodial growth
      associated processes. These are eliminated from the soma and proximal dendrites
      during the first postnatal week as part of a somatofugal process of dendritic
      maturation. Following neonatal axotomy, the postnatal elimination of growth
      associated processes was halted and new, axonal-like processes were seen to
      sprout from the soma and proximal dendrites in some of the axotomized
      motoneurones. These results indicate that synaptic interaction with the target
      muscle during the early postnatal period is essential for the maturation of the
      somatodendritic receptive surface of the motoneurone.

PMID- 9631461
TI  - Mesencephalic THmRNA-reduced expression by blocking axonal transport with
      colchicine.
AB  - Colchicine, an axonal transport blocking agent, was unilaterally injected in the
      medial forebrain bundle of rats. As early as 18 h after the injection a rapid
      decrease in TH-mRNA level was observed in the substantia nigra and the ventral
      tegmental area (SN/VTA) on the injected side. In contrast, TH protein levels
      remained stable for 48 h, and decreased later in both cells bodies and terminals
      (caudate/putamen). The number of TH-immunopositive cells in SN/VTA increased
      after colchicine equally in both sides, excluding a neurotoxic effect. These
      results suggest that TH gene expression is controlled by a retrogradely
      transported activating factor rather than by feedback inhibition by the end
      product, i.e. TH protein.

PMID- 9631462
TI  - NGF and LIF both regulate galanin gene expression in primary DRG cultures.
AB  - Both target-derived and injury-induced factors could be involved in the axotomy
      induced increases in galanin expression in dorsal root, ganglion (DRG) neurons.
      Galanin mRNA levels were studied in primary cultures of E13.5 embryos, grown for
      14 days in culture, in response to two candidate molecules, nerve growth factor
      (NGF) and leukemia inhibitory factor (LIF). In these cultures, NGF withdrawal
      alone resulted in a significant increase in galanin mRNA. Addition of LIF onto
      NGF-containing cultures did not produce a significant increase, while addition of
      LIF to NGF-deprived cultures caused an upregulation of galanin mRNA which was
      significantly stronger than that of NGF withdrawal alone. Thus, NGF withdrawal
      and LIF increase act together to up-regulate galanin gene transcription in DRG
      neurons.

PMID- 9631463
TI  - Hemispheric specialization for English and ASL: left invariance-right
      variability.
AB  - Functional magnetic resonance imaging (fMRI) was used to compare the cerebral
      organization during sentence processing in English and in American sign language
      (ASL). Classical language areas within the left hemisphere were recruited by both
      English in native speakers and ASL in native signers. This suggests a bias of the
      left hemisphere to process natural languages independently of the modality
      through which language is perceived. Furthermore, in contrast to English, ASL
      strongly recruited right hemisphere structures. This was true irrespective of
      whether the native signers were deaf or hearing. Thus, the specific processing
      requirements of the language also in part determine the organization of the
      language systems of the brain.

PMID- 9631464
TI  - Developmental changes in refractoriness of the neuromagnetic M100 in children.
AB  - Considerable evidence exists for developmental changes in latency and amplitude
      of the auditory evoked potential termed N100. However, it is widely recognized
      that the N100 wave comprises multiple, temporally overlapping neural generators,
      and few data are available addressing either individual generator development or
      mechanisms behind such change. Using magnetoencelphalographic (MEG) measurements
      of the magnetic analog of the N100 termed the M100, which derives primarily from
      supra-temporal auditory generators, it is demonstrated here that changes in the
      response of that waveform to manipulation of interstimulus interval (ISI) occur
      between the ages of 6 and 18 years of age.

PMID- 9631466
TI  - Amyloid beta-peptide(25-35) changes [Ca2+] in hippocampal neurons.
AB  - Insoluble aggregates of the amyloid beta-peptide (A beta) is a major constituent
      of senile plaques found in brains of Alzheimer disease (AD) patients. The
      detrimental effects of aggregated A beta is associated with an increased
      intracellular Ca2+ concentration ([Ca2+]i). We examined the effects of A beta(25
      35) on [Ca2+]i and intracellular H+ concentration ([H+]i) in single hippocampal
      neurons by real time fluorescence imaging using the Ca(2+)- and H(+)-specific
      ratio dyes, indo-1 and SNARF-1. Incubation of these cultures with A beta(25-35)
      for 3-12 days in vitro increased [Ca2+]i and [H+]i in large, NMDA-responsive
      neurons.

PMID- 9631465
TI  - Heat shock, but not the reactive state per se, induces increased expression of
      the small stress proteins hsp25 and alpha B-crystallin in glial cells in vitro.
AB  - The stress proteins hsp25 and alpha B-crystallin are found in increased
      concentrations in reactive astrocytes of brains undergoing neurodegeneration. In
      order to characterize this reaction, we investigated the expression of hsp25 and
      alpha B-crystallin during growth and after stress (heat shock) in glial cells in
      vitro. In primary rat brain cultures, hsp25 was present in actively dividing
      astrocytes that were positive for glial fibrillary acidic protein. alpha B
      crystallin was found predominantly in oligodendrocytes. Heat shock resulted in
      increased concentrations of hsp25 and alpha B-crystallin in astrocytes, without
      any detectable changes in intracellular localization, as detectable with confocal
      laser microscopy. These results indicate that a neurodegeneration-related
      increase of the small stress proteins in astrocytes in independent of gliosis per
      se, and may be a disease-related event.

PMID- 9631467
TI  - Ecto-nucleotidases terminate purinergic signalling in the cochlear endolymphatic
      compartment.
AB  - There is strong evidence for a purinergic signalling system in the inner ear
      which regulates auditory sensitivity. This study describes the terminating
      mechanism for purinergic signalling in the cochlear endolymphatic compartment via
      ecto-nucleotidases. Exogenous ATP was introduced into the scala media (SM) of the
      isolated, perfused guinea-pig cochlea, and the effluent was assayed for the
      adenine nucleotide metabolites by reverse-phase HPLC. Tissue viability was
      confirmed by fluorescence imaging of cochlear tissues. Extracellular ATP
      degradation to adenosine was Ca2+/Mg2+ dependent, and was not affected by
      inhibitors of intracellular ATPases and non-specific alkaline phosphatase. High
      azide concentration (5 mM) and suramin produced an inhibitory effect on ATP
      hydrolysis, consistent with inhibition of E-type ATPase activity. The Vmax of ATP
      hydrolysis (2564 mumol min-1 SM-1) was indicative of high ecto-ATPase activity.
      Our results support the role of ecto-nucleotidases as a principal mechanism for
      termination of purinergic signalling within SM, a compartment of the cochlea
      showing considerable P2X receptor expression.

PMID- 9631468
TI  - Differential activation of dorsal basal ganglia during externally and self paced
      sequences of arm movements.
AB  - The basal ganglia are thought to be critically involved in motor control.
      However, the relative contributions of the various sub-components are not known.
      Although, in principle, functional magnetic resonance imaging (fMRI) provides
      adequate resolution to image the basal ganglia at the spatial scale of the
      individual nuclei, activating these nuclei with fMRI has proven to be difficult.
      Here we report two tasks, involving externally and self paced sequences of arm
      movements, which resulted in significant activation of contralateral posterior
      (post-commissural) putamen and globus pallidus. This activation did not
      significantly differ between the tasks. In contrast, significant activation of
      the contralateral and ipsilateral anterior caudate and anterior putamen was
      observed only during externally paced arm movements. These results suggest a
      dissociation in the roles of the anterior and posterior dorsal basal ganglia: the
      anterior caudate and putamen may be involved in sensory to motor mapping and the
      posterior putamen and globus pallidus may be involved in the motor response
      itself. The findings support the hypothesis that the basal ganglia may be
      involved in gating sensory influences onto motor areas.

PMID- 9631469
TI  - Modulation of neuropeptide Y overflow by leptin in the rat hypothalamus, cerebral
      cortex and medulla.
AB  - This study examined whether leptin can exert inhibitory actions on brain NPY
      overflow in Sprague-Dawley and in lean and obese Zucker rats, and tested the site
      specificity of the effect. Slices of rat hypothalamus, cerebral cortex and
      medulla oblongata were perfused with modified Krebs buffer containing either
      leptin or KCl. Depolarization of tissues with 40 mM KCl elicited a significant
      doubling of NPY overflow in all brain regions tested. At 1 microM, leptin
      significantly reduced NPY overflow only in the rat hypothalamus, while at 3
      microM, leptin reduced NPY overflow from all regions. However, no effect of 1
      microM leptin was observed in the hypothalamus of obese Zucker rats: this
      insensitivity to leptin is in keeping with their genetic defect. In conclusion,
      the inhibitory effect of leptin on hypothalamic NPY overflow provides further
      evidence for important modulatory actions between these two feeding mediators.
      Moreover, the effect of leptin observed in the cerebral cortex and medulla
      oblongata supports a role of leptin in brain regions other than the hypothalamus.

PMID- 9631470
TI  - The role of the left inferior temporal cortex for visual pattern discrimination-
      a PET study.
AB  - We measured regional cerebral blood flow using positron emission tomography in
      seven normal volunteers during discrimination tasks for visual patterns. For the
      'attention to right or left' tasks, the subjects were instructed to press a key
      when sample and test stimuli presented in the right or left visual fields,
      respectively, were identical. In the control task, subjects were instructed to
      press a key on every second presentation of the test stimulus. Both
      discrimination tasks activated the same area in the inferior temporal sulcus of
      the left hemisphere. The results indicate that the left inferior temporal cortex
      plays a dominant role in the discrimination of visual pattern in right handed
      subjects.

PMID- 9631472
TI  - Purification of PASII/PMP22--an extremely hydrophobic glycoprotein of PNS myelin
      membrane.
AB  - PASII/PMP22 protein (mol. wt 22 kDa, pI 8.8) is an abundant and extremely
      hydrophobic glycoprotein of PNS myelin which is solubilized effectively by SDS.
      In humans, this protein is involved in hereditary neuropathies. Here we describe
      a simple method for purification of PASII/PMP22, suitable for crystallization
      trials. We usually obtained 10-20 mg PASII/PMP22 from 10 g bovine spinal roots.
      It is notable, that the original protocol was designated for purification of P0
      myelin glycoprotein, and purification of PASII/PMP22 is a bonus. Extensive
      crystallization trials are in progress.

PMID- 9631471
TI  - Electron spin resonance measure of brain antioxidant activity during
      ischemia/reperfusion.
AB  - An electron spin resonance technique was used to measure cerebral antioxidant
      activity during asphyxial cardiac arrest and reperfusion. There were significant
      decreases in ascorbate (48%), glutathione (44%), total thiols (42%), protein
      thiols (38%) and alpha-tocopherol (26%) in the hippocampus 10 min after
      reperfusion (p < 0.05 vs respective baselines) but not during asphyxial cardiac
      arrest. The levels of antioxidants returned to baseline values by 120 min after
      reperfusion. The results support the hypothesis that reperfusion from asphyxial
      cardiac arrest, but not arrest alone, produced a significant oxidative stress as
      reflected by a depletion of both water and lipid soluble antioxidants.
      Furthermore, antioxidant depletion was transient, with normal antioxidant levels
      observed 120 min, 24 h and 72 h after reperfusion.

PMID- 9631473
TI  - The role of CRF2 receptors in corticotropin-releasing factor- and urocortin
      induced anorexia.
AB  - The experiments presented in this study were designed to assess corticotropin
      releasing factor (CRF) receptor subtype mediation of CRF- and urocortin (UCN)
      induced decrease in food intake. Male Sprague-Dawley rats were treated with
      antisense and sense oligonucleotides (ON) to CRF2 receptor mRNAs for 36 h and
      then received an intracerebroventricular (i.c.v.) injection of CRF, UCN (3
      micrograms) or saline. Antisense treatment significantly attenuated CRF- and UCN
      induced suppression in food intake and HPA activation. Administration of CRF1
      receptor antagonist did not affect the decrease in food intake or activation of
      the HPA axis induced by i.c.v. infusion of 3 micrograms CRF. The data suggest
      that down-regulation of CRF2 receptors selectively attenuates CRF- and UCN
      induced anorexia and hypothalamo-pituitary-adrenocortical activation in rats.

PMID- 9631474
TI  - Two vocalization-related subregions in the midbrain periaqueductal gray of the
      guinea pig.
AB  - Vocal communications are well-developed in guinea pigs: they emit a separation
      call when isolated from the conspecifics, and vocalize mating calls during sexual
      activities. Similar calls were induced by the electrical stimulation of the
      midbrain periaqueductal gray (PAG) and the locations where the separation and
      mating calls were induced were segregated in the PAG. The morphological findings
      demonstrated that the PAG subregion where the separation call was induced
      receives massive input from the anterior cingulate cortex (which is related to
      social attachment behavior), while the subregion where the mating call was
      emitted has inputs mainly from the medial hypothalamus (related to sexual
      behaviors), suggesting that guinea pigs used multiple neuronal networks for
      various species-specific calls.

PMID- 9631475
TI  - Transplantation of multipotent progenitors from the adult olfactory epithelium.
AB  - Mammalian olfactory epithelium produces new neurons rapidly throughout adulthood.
      Here, we demonstrate that precursor cells harvested from the adult olfactory
      epithelium, when transplanted into the nasal mucosa of host rats exposed
      previously to an olfactotoxic gas, engraft and participate in neuroepithelial
      reconstitution. In contrast to their normal neuronal fate in situ, grafted
      precursors harvested from bulbectomized donors produced non-neuronal cells as
      well as neurons. These results demonstrate that epithelial precursors activated
      following olfactory bulbectomy are not irreversibly committed to making neurons.
      Thus, olfactory progenitors are subject to a form of feedback control in vivo
      that regulates the types of cells that they produce within a broader-than
      neuronal repertoire.

PMID- 9631476
TI  - Ginseng improves strategic learning by normal and brain-damaged rats.
AB  - Adult rats were prepared with either sham or medial prefrontal cortex lesions and
      administered, beginning on the third post-operative day, either, 0, 40, or 80 mg
      kg-1 crude ginseng extract suspended in saline daily for the next 30 days. Later,
      kinetic functions were evaluated on an elevated rotating rod. No long-term
      influences of the treatments were observed on this task. Significant positive
      influences of ginseng were observed in the position reversal task. The learning
      deficits observed in the saline control brain-damaged rats were significantly
      attenuated in the ginseng-treated animals. An analysis of trial 2 response
      accuracy across reversals revealed enhanced cognitive abilities (i.e. acquisition
      of a win-stay, lose-shift strategy) in both the brain damaged and sham control
      rats administered ginseng. Generally, administration of the higher dose resulted
      in better performance in the learning paradigm. The exact mechanism responsible
      for these promising results remains to be discovered. Several possible mechanisms
      are discussed.

PMID- 9631478
TI  - Tetrahydroaminoacridine, a cholinesterase inhibitor, and D-cycloserine, a partial
      NMDA receptor-associated glycine site agonist, enhances acquisition of spatial
      navigation.
AB  - The present study examines the efficacy of single and combined treatments with an
      antiocholinesterase, tetrahydroaminoacridine (THA, i.p.), and a glycine-B site
      partial agonist, D-cycloserine (DCS, i.p.) to alleviate water maze (WM) spatial
      navigation defect induced by medial septal (MS) lesion. THA 3 and DCS at 3 or 10
      mg/kg improved acquisition of the WM test, but only DCS improved spatial bias.
      These drugs had no effect on consolidation. A combination of THA 3 and DCS 10
      mg/kg enhanced WM acquisition more effectively than either of the treatments on
      their own. This suggests that combined modulation of acetylcholine and NMDA
      mechanisms may have greater therapeutic effect to stimulate cognitive
      dysfunctions.

PMID- 9631477
TI  - Intracellular Ca2+ and adaptation of voltage responses to light in Hermissenda
      photoreceptors.
AB  - Fluorescent imaging of Ca2+ and intracellular recordings were used to assess Ca2+
      increases and voltage responses during light presentations in Hermissenda B
      photoreceptors. Ca2+ levels increased and were sustained during a relatively long
      exposure to light. Repeated presentations of a brief light induced an elevation
      of intracellular Ca2+ that persisted throughout short interlight intervals, but
      which dissipated during long interlight intervals. In all instances, the
      magnitude of the intracellular Ca2+ signal was inversely related to the amplitude
      of the light-induced generator potential. Blocking of voltage-dependent Ca2+
      channels did not significantly affect the magnitude of the Ca2+ signal,
      suggesting that the intracellular Ca2+ response arises primarily from release
      from intracellular stores. These results indicate that Ca2+ plays an important
      role in the modulation of the voltage responses to light, acting to suppress the
      response during repetitive or prolonged stimulation.

PMID- 9631479
TI  - Localization of glutamate receptors in dorsal horn of rat spinal cord.
AB  - Immunocytochemical localization of metabotropic glutamate receptors (mGluRs) and
      ionotropic glutamate receptors (NMDA-type: NMDAR1 and NMDAR2A-C; AMPA-type: GluR1
      4) was performed on sections of rat dorsal horn. Immunoreactivity for mGluR1
      alpha was detected in laminae I-III of the dorsal horn, whilst mGluR2/3
      immunoreactivity was detected primarily in lamina III. Immunoreactivity for
      NMDAR1, GluR1, GluR2, GluR2/3, GluR4 and GluR5/6/7 was strongly localized in
      neuronal elements of laminae I-III. Immunoreactivity for NMDAR2B was localized in
      laminae I-III. No mGluR5, NMDAR2A and NMDAR2C immunoreactivity was detected. In
      addition, immunoreactivity for receptors was found to co-localize with
      immunoreactivity for glutamate in the dorsal horn. The present results indicate
      that glutamate receptors are differentially localized in neuronal elements of
      dorsal horn where receptor-neurotransmitter interaction takes place.

PMID- 9631480
TI  - Three time windows for amnestic effect of antibodies to cell adhesion molecule L1
      in chicks.
AB  - The L1/NgCAM cell adhesion molecule is involved in neurite outgrowth, axonal
      fasciculation and cell migration in the nervous system. We studied the effects of
      antibodies against L1 injected intracranially at various times before and after
      training 2-day-old chicks in a visual categorization task. Memory retention was
      tested 24 h post-training. Anti-L1 antibodies impaired task retention only when
      administered in three restricted time windows: immediately before training, at
      about 5.5 h after training and from 15 to 18 h after training. No amnesia was
      produced by injections before, between or after these sensitive periods (from -1
      to +21 h relative to training). These results indicate that there are multiple
      post-training periods during which L1 is involved in the formation of long-term
      memory.

PMID- 9631481
TI  - Concept activation and coordination of activation procedure require two different
      networks.
AB  - In the present study, we used EEG-coherence analysis to assess general regional
      changes in neuronal activity related to semantic retrieval, testing the
      hypothesis that concept activation and coordination procedures are
      neurobiologically distinguishable. Four subjects had to decide whether or not a
      capital letter and a lower case letter have the identical name (e.g. Aa). This
      task requires two mental procedures: (i) the activation of concepts and (ii)
      their coordination, particularly when the interstimulus interval is shorter than
      the duration of concept activation. This memory retrieval of a concept appears to
      be subserved by two distinct networks: the left parietotemporal region for
      concept activation and the prefrontal region for coordination.

PMID- 9631482
TI  - The hydroxyl radical scavenger Nicaraven inhibits glutamate release after spinal
      injury in rats.
AB  - Neuronal degeneration after trauma is mediated in part by release of excitatory
      amino acids (EAAs) and oxygen free radicals (OFR). We evaluated the effect of
      i.v. treatment with a hydroxyl radical scavenger ((+/-)-N,N'
      propylenedinicotinamide; AVS) and spinal hypothermia (33 degrees C) on spinal CSF
      glutamate release after spinal trauma. In a control group, spinal compression
      evoked at 10 min a significant increase (5-fold) in glutamate which declined over
      4 h (2.1-fold). AVS treatment attenuated glutamate release but had no additive
      effect. These data suggest that this compound can be effective in modulating
      spinal excitotoxicity resulting from increased OFR synthesis and corresponding
      potentiation of EAA release.

PMID- 9631483
TI  - Neutrophin switching in spinal motoneurons of amyotrophic lateral sclerosis.
AB  - To clarify the roles of neurotrophins in the human spinal motoneurons, with
      special reference to amyotrophic lateral sclerosis (ALS), we studied the
      immunohistochemical localizations of neurotrophins and their receptors in spinal
      cords of patients with ALS and compared them with controls. In the controls, the
      majority of motoneurons showed BDNF-, NT3-, trkB- and trkC-like immunoreactivity
      (-LI) suggesting that the motoneurons receive an autocrine regulation by both
      BDNF and NT3. In ALS patients, about three-quarters of the motoneurons had
      degenerated and the remaining motoneurons showed significantly decreased BDNF-LI,
      increased NGF- and trkA-LI. These findings indicated neurotrophin-switching in
      the remaining spinal motoneurons of ALS patients from BDNF and NT3 responsive to
      NGF responsive.

PMID- 9631484
TI  - The uterine environment enhances cognitive competence.
AB  - Genetically identical mouse embryos were transferred into same-strain uteri
      (transfer controls) or into hybrid uteri. A third group was not transferred. When
      adult, the mice were given a series of behavioral tests. In-strain transfer
      controls differed from non-transfer mice only on two activity measures, and did
      not differ on any cognitive variable. In contrast, mice reared in hybrid uteri
      were found to be superior to in-strain transfer mice on discrimination learning.
      Lashley maze learning and Morris maze learning; they also showed better
      adaptation in an avoidance learning shuttlebox. To our knowledge this is the
      first study showing that the uterine environment can have a general enhancing
      effect upon cognitive competence across a broad range of behaviors.

PMID- 9631485
TI  - Neural activity in areas V1, V2 and V4 during free viewing of natural scenes
      compared to controlled viewing.
AB  - Under natural viewing conditions primates make frequent exploratory eye movements
      across complex scenes. We recorded neural activity of 62 cells in visual areas
      V1, V2 and V4 in an awake behaving monkey that freely viewed natural images.
      About half of the cells studied showed a modulation in firing rate following some
      of the eye movements made during free viewing, though the proportions showing a
      discernible modulation varied across areas. These cells were also examined under
      controlled viewing conditions in which gratings or natural image patches were
      flashed in and around the classical receptive field while the animal performed a
      fixation task. Activity rates were generally highest with flashed gratings and
      lowest during free viewing. Flashed natural image patches evoked responses
      between these two extremes, and the responses were higher when the patches were
      confined to the classical receptive field than when they extended into the non
      classical surround. Thus the reduction of activity during free viewing relative
      to that obtained with flashed gratings is partly attributable to natural images
      being less effective stimuli and partly to suppressive spatio-temporal neural
      mechanisms that are important during natural vision.

PMID- 9631486
TI  - Depressed p34cdc2 kinase activity and G2/M phase arrest induced by diallyl
      disulfide in HCT-15 cells.
AB  - The present studies reveal the antiproliferative property of diallyl disulfide
      (DADS) in cultured human colon tumor cells (HCT-15) relative to its ability to
      decrease the proportion of cells in the G1 phase and increase the proportion of
      cells in the G2/M phase. The shift in the proportion of cells blocked in the G2/M
      phase increased as the concentration and duration of DADS exposure increased.
      Refeeding DADS-treated cells (50 microM) with complete medium without DADS
      resulted in a return to normal proliferation rates. Consistent with the G2/M
      phase arrest, DADS exposure inhibited p34cdc2 kinase activity within four hours
      of treatment. The maximum depression in p34cdc2 kinase activity (53%) occurred
      when 25 microM DADS was added to the medium. The present studies suggest that
      depressed p34cdc2 kinase activity is likely one of the early cellular events that
      may account for the antiproliferative property of DADS.

PMID- 9631487
TI  - Slow-release pellets of sodium butyrate increase apoptosis in the colon of rats
      treated with azoxymethane, without affecting aberrant crypt foci and colonic
      proliferation.
AB  - We investigated whether sodium butyrate, administered orally as gastroresistant
      slow-release pellets to rats, could affect markers of colon carcinogenesis. F344
      male rats were fed a high-fat diet (230 g/kg corn oil, wt/wt) and treated with
      two injections (1 wk apart) of azoxymethane (15 mg/kg sc) or saline. Rats were
      then divided into two groups: one received the diet with 1.5% (wt/wt) sodium
      butyrate for 10 weeks to provide 150 mg butyrate/day, and one group received no
      butyrate. At the end of this period, rats were sacrificed, and colonic
      proliferative activity, number of aberrant crypt foci (ACF), and apoptosis were
      assessed in the colon. The proliferative activity and ACF induction were not
      affected by butyrate pellet administration. On the contrary, in rats treated with
      butyrate, apoptotic index increased from 0.12 +/- 0.12 to 0.81 +/- 0.10 (means +/
      SE, p < 0.05). The short-chain fatty acid concentration was significantly
      increased in the feces of rats treated with butyrate. In conclusion, the increase
      in the mucosal apoptotic index suggests that gastroresistant butyrate pellets
      have a beneficial effect against colon carcinogenesis. However, because butyrate
      pellets did not modify proliferation or ACF induction, this conclusion should be
      confirmed in long-term carcinogenesis experiments.

PMID- 9631488
TI  - Meal frequency and coffee intake in colon cancer.
AB  - Several studies suggested that frequent eating may increase colon cancer risk. To
      further clarify this issue, a case-control study was carried out in six areas of
      Italy on 1,225 incident cases < 75 years of age with histologically confirmed
      colon cancer and 4,154 control subjects. The controls were hospitalized for
      acute, nonneoplastic conditions unrelated to long-term dietary modifications.
      After allowance for education, physical activity, intake of vegetables, and major
      energy sources, there was a trend of increasing risk with increasing eating
      frequency (odds ratio for > or = 4 vs. < or = 2 daily meals = 1.24). Coffee
      intake, which was inversely associated with cancer risk, exerted a modification
      effect, with an odds ratio of 1.89 for frequent eaters who drank fewer than two
      cups of coffee per day. Frequent eating increases, whereas high coffee intake
      decreases, the excretion of bile acids, which are suspected to be carcinogenic to
      the colon. Thus, it is conceivable that frequent coffee intake may counterbalance
      the effect of frequent eating.

PMID- 9631489
TI  - Suppressive effect of low amounts of safflower and perilla oils on
      diethylnitrosamine-induced hepatocarcinogenesis in male F344 rats.
AB  - We have investigated the modulating effects of low amounts of dietary oils rich
      in polyunsaturated fatty acids (PUFA) on diethylnitrosamine (DEN)-induced
      hepatocarcinogenesis in male F344 rats. A total of 112 animals were divided into
      eight groups. Groups 1-4 were given drinking water containing 40 ppm DEN for five
      weeks. Groups 5-8 served as controls without DEN treatment. Groups 1 and 5 were
      fed a basal diet containing 5% beef tallow, Groups 2 and 6 were fed a 5% olive
      oil diet, Groups 3 and 7 were fed a 5% safflower oil diet, and Groups 4 and 8
      were fed a 5% perilla oil diet for 21 weeks, starting 1 week before DEN exposure.
      Beef tallow, olive oil, safflower oil, and perilla oil are rich in saturated
      fatty acids, a monounsaturated fatty acid, n-6 PUFA, and n-3 PUFA, respectively.
      All rats were killed 20 weeks after the start of the experiment. Incidences of
      hepatocellular adenoma and carcinoma were 100% in DEN-treated groups,
      irrespective of dietary oils. Multiplicities of adenomas in Groups 3 and 4 were
      significantly (p < 0.05) lower than in Groups 1 and 2. Multiplicity of carcinoma
      in Group 3 was significantly (p < 0.05) lower than in Group 1. Mean volumes of
      placental glutathione S-transferase-positive foci per liver and the number of
      argyrophilic nucleolar organizer region proteins per nucleus in the liver tumors
      were significantly (p < 0.05) lower in Groups 3 and 4 than in Groups 1 and 2. ras
      mRNA expression in liver neoplasms was also suppressed significantly (p < 0.05)
      in Groups 3 and 4 compared with Groups 1 and 2. Significantly (p < 0.05) higher
      levels of n-6 and n-3 PUFA in the phospholipid fraction of the liver were found
      in Groups 3 and 4, respectively, than in the other groups. In contrast, a
      significantly (p < 0.05) decrease in monounsaturated fatty acid was observed in
      Groups 3 and 4 compared with Groups 1 and 2. These results suggest that safflower
      oil and perilla oil, rich in n-6 and n-3 PUFA, respectively, alter the membrane
      fatty acid composition of the liver and suppress the development of liver cell
      carcinoma in rats.

PMID- 9631490
TI  - Relative contribution of calories from dietary fat, carbohydrate, and fiber in
      the promotion of DMBA-induced mammary tumors in Sprague-Dawley rats.
AB  - It is well known that caloric restriction inhibits, whereas excess calories
      promote, mammary tumorigenesis in rats. However, the relative contribution to
      carcinogenesis by calories derived from fat or from carbohydrate are not well
      established. To determine the relative effects of calories from fat or from
      carbohydrate, as well as any interaction of dietary fiber on the promotion of
      7,12-dimethylbenz[a]anthracene-induced mammary tumors, we fed isocalorically nine
      diets containing different ratios of fat, carbohydrate, and fiber to female
      Sprague-Dawley rats treated with 7,12-dimethylbenz[a]anthracene (30/group). Under
      conditions of isocaloric consumption, at or near ad libitum feeding, calories
      from dietary fat had approximately twofold greater promoting effect on final body
      weight and tumor incidence than calories derived from dietary carbohydrate.
      Dietary fiber had an inhibitory effect on tumor development, but the effect was
      evident only in the high-fat groups. Logistic regression analysis of tumor
      incidence gave beta-coefficient estimates for the relative effects of fat,
      carbohydrate, and fiber of 0.866, 0.189, and -4.281, respectively. Time-to-tumor
      analysis by the Weibull model indicated beta-estimates of 3.016, 3.324, and 5.825
      for dietary fat, carbohydrate, and fiber, respectively, indicating that fat
      shortens and fiber increases the length of time to tumor. The statistical model
      derived from these results also indicates a significant synergistic interaction
      of dietary fat and carbohydrate on final body weight and tumor incidence.

PMID- 9631491
TI  - Vitamin E and colon cancer: is there an association?
AB  - The role of vitamin E in the etiology and prevention of colon cancer is not
      clear. It is possible that various forms of vitamin E may act differently in
      colon tissue and may be effective chemopreventive agents. Previous reports of
      vitamin E and colon cancer have focused on alpha-tocopherol and have not
      considered other dietary forms of vitamin E. Data from a study of 1,993 cases and
      2,410 controls were used to evaluate the associations between the four most
      common forms of dietary vitamin E and supplemental vitamin E and colon cancer.
      After adjusting for other health and life-style factors, we did not observe a
      statistically significant association between dietary tocopherols and colon
      cancer. There were, however, suggestions of an inverse association between total
      alpha-tocopherol equivalents and colon cancer among women diagnosed with colon
      cancer before the median age of the control population, 67 years [odds ratio (OR)
      = 0.66, 95% confidence interval (CI) = 0.36-1.22] and a direct association
      between gamma-tocopherol and colon cancer among these women (OR = 1.44, 95% CI =
      0.92-1.93). Women diagnosed with colon cancer when > or = 67 years of age
      appeared to have some protection from use of vitamin E supplements (OR = 0.80,
      95% CI = 0.56-1.15). These data offer only limited support for a protective
      effect of vitamin E and colon cancer after adjustment for other health and life
      style factors.

PMID- 9631492
TI  - Usual consumption of plant foods containing phytoestrogens and sex hormone levels
      in postmenopausal women in Wisconsin.
AB  - Consumption of phytoestrogens may reduce hormone-dependent cancer risk through
      alterations in the actions or metabolism of steroid hormones. Studies in humans
      of phytoestrogen-hormone interactions have been limited and inconsistent.
      Relations between the consumption of phytoestrogen-containing foods and serum sex
      hormones and sex hormone-binding globulin were studied in a population-based
      sample of postmenopausal women who participated in the Nutritional Factors in Eye
      Disease Study of the Beaver Dam Eye Study. Information on phytoestrogen
      containing foods (broccoli, carrots, cauliflower, chili, dark bread, peas, and
      dried beans) was collected by interviewer-administered food-frequency
      questionnaires. Estrone, sex hormone-binding globulin, dehydroepiandrosterone
      sulfate, and total and free testosterone were measured. Analyses included 246
      postmenopausal women not taking hormone replacements. Partial correlations
      between hormones and intake of phytoestrogen-containing foods were computed, with
      adjustment for age, body mass index, years since menopause, and total energy
      intake. Number of standard servings per week of whole-grain products from the
      dark bread group was inversely associated with total testosterone (r = -0.20, p =
      0.002). Although not statistically significant, other hormones displayed similar
      inverse associations with dark bread consistent with a common metabolic pathway.
      Although the magnitude of association was small, the data are consistent with the
      possibility that consumption of some phytoestrogen-containing foods may affect
      levels of testosterone in postmenopausal women.

PMID- 9631493
TI  - Alcohol intake and risk of cancers of the colon and rectum.
AB  - The relationship between alcohol drinking (mainly wine) and risk of colon and
      rectal cancer was considered in a case-control study conducted between 1991 and
      1996 in six Italian centers. Cases were 1,225 patients < 75 years of age with
      histologically confirmed cancer of the colon and 728 patients with cancer of the
      rectum; controls were 4,154 patients admitted to hospital for a wide spectrum of
      acute, nonneoplastic diseases. Compared with never drinkers, the odds ratios (OR)
      for current drinkers in the higher quintile of total alcohol intake (> 51.82 g
      ethanol/day) were 1.01 for colon cancer and 0.90 for rectal cancer, and those for
      ex-drinkers were 1.20 and 1.07, respectively. The OR for wine drinkers in the
      highest quartile of intake were 1.07 for colon cancer and 0.97 for rectal cancer.
      No association was found with duration of the habit, time since starting, or age
      at starting. Among ex-drinkers, no association appeared with time since stopping.
      No significant heterogeneity was found across strata of age at diagnosis, sex,
      education, smoking status, physical activity, family history of colorectal
      cancer, beta-carotene, vitamin C, coffee, total fiber and folate intake, and
      number of meals per day. No significant association appeared for various
      intestinal subsites.

PMID- 9631494
TI  - Feeding of a well-cooked beef diet containing a high heterocyclic amine content
      enhances colon and stomach carcinogenesis in 1,2-dimethylhydrazine-treated rats.
AB  - Epidemiologic studies have linked the consumption of red meat and the consumption
      of highly browned meats containing high levels of heterocyclic aromatic amines
      (HCAs) to increased risk of colorectal cancer or polyps. The present study
      determined the effects of long-term feeding of beef-containing diets with low and
      high levels of HCAs (in the context of a low or high beef tallow diet) on a
      standard 1,2-dimethylhydrazine (DMH)-induced colon tumorigenesis protocol. Very
      lean beef was cooked by a variety of methods at different temperatures, and the
      levels of the major HCAs (2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, 2-amino
      3,4,8-trimethylimidazo[4,5-f]quinoxaline, and 2-amino-1-methyl-6
      phenylimidazo[4,5-f]pyridine) were measured by high-performance liquid
      chromatography. Diets incorporating beef containing low or high levels of HCAs
      were fed for 12 weeks, during which DMH was administered to induce colon tumors,
      followed by various dietary regimens as promotional stimuli. Feeding of a beef
      diet high in HCAs resulted in more DMH-induced colon adenocarcinomas, but only in
      the context of a low-fat diet. The high-HCA diets increased stomach tumors in all
      DMH-treated rats. An apparent interaction of high HCA with a high fat level
      reduced the colon tumor incidence and tumor numbers in those diets containing
      both factors. These results support the epidemiologic data linking well-cooked
      meat to increased risk for colon and stomach cancer, but the role of dietary fat
      level remains puzzling.

PMID- 9631495
TI  - Absence of PhIP adducts, p53 and Apc mutations, in rats fed a cooked beef diet
      containing a high level of heterocyclic amines.
AB  - Meat cooked at high temperatures contains mutagens and carcinogens known as
      heterocyclic amines (HCA). Cooking temperature and time determine the amount of
      HCA produced. The present study examined the DNA of liver, colon, and stomach
      from rats fed a high level of HCA for 27 weeks. Male Sprague-Dawley rats were fed
      a high-fat AIN-76A-based diet containing 60% by weight cooked beef containing a
      high level of HCA, especially 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
      (PhIP, 72 ng/g cooked beef), the most abundant HCA in cooked meat products. At
      the end of 27 weeks the rats were terminated, and small portions of liver, colon,
      and stomach were quick-frozen in liquid nitrogen. The DNA was isolated from the
      thawed tissue by phenol-chloroform extraction, and the genomic DNA was analyzed
      for the presence of PhIP adducts by 32P-postla-beling analysis. The DNA was also
      used in polymerase chain reactions to amplify the rat p53 and Apc genes, then
      direct dye-terminator DNA sequencing was carried out. Results showed no PhIP
      adducts in any tissue. In addition, no signature p53 or Apc gene mutations were
      seen in colon or stomach DNA. These results indicate that the high level of HCA
      present in a diet of well-cooked meat does not cause 1) persistent PhIP adducts
      similar to those produced by feeding pure PhIP at high doses or 2) p53 and Apc
      gene mutations in nontumor tissue.

PMID- 9631496
TI  - Effect of soy-derived isoflavonoids on the induced growth of MCF-7 cells by
      estrogenic environmental chemicals.
AB  - Isoflavonoids are natural plant compounds and possess antitumorigenic properties.
      Many environmental chemicals have been found to be estrogenic and can enhance
      tumor growth in estrogen receptor-positive cells. In the present study, the
      effects of genistein, daidzein, biochanin A, formononetin, and equol on the
      proliferation of estrogen receptor-positive MCF-7 cells induced by synthetic
      chemicals 1-(o-chlorophenyl)-1-(p-chlorophenyl)-2,2,2-trichloroethane (o,p'-DDT),
      4-nonylphenol (4-NP), and 5-octylphenol (5-OP) found in the environment were
      investigated. Genistein, biochanin A, equol, and to some extent daidzein, but not
      formononetin, at < 10 microM can enhance the growth of MCF-7 cells in the absence
      of environmental chemicals. Formononetin was toxic to MCF-7 cells at the tested
      concentrations. The environmental chemicals 4-NP, 5-OP, and o,p'-DDT and the
      natural estrogen 17 beta-estradiol at 5, 5, and 10 microM and 5 nM, respectively,
      induced proliferation of MCF-7 cells. In the presence of isoflavonoids (> 25
      microM), the environmental chemical-induced cell proliferation was inhibited.
      Individually, genistein (IC50 = 25-33 microM) was the most potent inhibitor
      against the induced proliferation of MCF-7 cells of the isoflavonoids needed for
      a 50% suppression of growth induced by 4-NP, 5-OP, and o,p'-DDT. A mixture of
      isoflavonoids was the most potent inhibitor against the induced proliferation.
      Estrogen receptor-dependent and -independent pathways could be involved in the
      inhibitory actions of isoflavonids. Because it is impossible to have a chemical
      free environment, the in vitro data presented here are of practical importance to
      develop evolving dietary strategies and tactics against the adverse health
      effects of environmental chemicals.

PMID- 9631497
TI  - [The importance of concomitant compounds in plant extracts].
AB  - Plant extracts are multi-composed mixtures that can be subdivided into main
      active substances and concomitant compounds. Concomitant compounds are called co
      effectors because they can change the physicochemical properties of the main
      active substances and therefore influence the biopharmaceutical parameters, e.g.
      solubility and bioavailability. The composition and the properties of plant
      extracts depend on a multitude of different factors such as quality and degree of
      reduction of the plant, and the process of extraction and drying. Concomitant
      compounds affect the physical and chemical stability of plant extracts. The
      hygroscopicity also depends on the composition of the concomitant compounds. It
      is an important property for the further processing of the plant extract to solid
      dosage form, e.g. tablets. Solubility and dissolution rate can be influenced by
      the concomitant compounds. Both properties are important for the absorption of
      the active substances though in many cases the responsible substances and
      mechanisms are still unknown. Solubilisation by surface-active agents, formation
      of soluble drug-concomitant compound-associates and solid dispersion, in which
      the drug is finely dispersed or X-ray amorphous, are often responsible for the
      increased solubility. Improved wettability in the presence of the concomitant
      compounds results in better dissolution. Supersaturated solutions of the active
      substances are stabilized for months by inhibition of crystallization. Numerous
      examples are known for influencing the absorption by natural concomitant
      compounds. The absorption is enhanced by the increased amount of dissolved drug
      or by the alteration of membrane permeability. Adsorption or complex formation
      with the concomitant compounds decrease the absorption rate, in some cases also
      the extent of absorption.

PMID- 9631498
TI  - Sugarhydrazones of 2-hydrazinoquinolines and their antimicrobial activity.
AB  - Sugar hydrazones from 2-hydrazinoquinoline, 2-hydrazino-6-methyllepidine, 6
      chloro-2-hydrazino lepidine, 7-chloro-2-hydrazinolepidine, and 7-chloro-2
      hydrazino-3-nitroquinoline were prepared. Their acetylation, benzoylation,
      periodate oxidation, oxidation with lead tetraacetate and bromination have been
      investigated. The antimicrobial activities of the hydrazones were evaluated. Some
      compounds showed moderate activity.

PMID- 9631499
TI  - Synthesis, lipophilicity and antimicrobial properties of some O-(5-aryl-1,2,4
      triazol-3-yl-ethyl)benzaldoximes and O-(5-aryl-1,3,4-oxydiazol-2-yl
      ethyl)benzaldoximes.
AB  - The synthesis of benzaldehyde oximethers with suitably substituted 1,2,4
      triazoles and 1,3,4-oxadiazoles from the corresponding benzaldoximes is
      described. The lipophilicity of the compounds was measured as well as their
      antimicrobial and antifungal activity in vitro. Certain compounds showed
      relatively significant activity against Bacillus subtilis.

PMID- 9631500
TI  - Evaluation of hair root analysis for acute phencyclidine poisoning and behavior
      of phencyclidine metabolites in rat hair root.
AB  - We evaluated the usefulness of hair root analysis to diagnose acute phencyclidine
      (PCP) poisoning. Male rats were i.p. administered acute poisonous doses (80, 100
      and 120 mg/kg) of PCP hydrochloride and the hair roots were plucked out with hair
      nippers at certain times after administration. The hair root samples were
      extracted with methanol/HCl. After evaporation of the solvent, the residue was
      derivatized with N,O-bis(trimethylsilyl) acetamide and analyzed with GC/MS. PCP
      was detected at high concentrations (up to 181.7 ng/mg) from all samples. The
      peak concentrations at every dose were observed at 6 h. The concentrations of PCP
      in the rat hair roots increased dose-dependently in the range of the doses. 1-(1
      Phenylcyclohexyl)-4-hydroxypiperidine (PCHP) and trans-1-phenyl-1(4'
      hydroxypiperidino)-4-cyclohexanol (t-PCPdiol) were also detected from 5 and 15
      min to 48 h after administration, respectively. It is concluded that hair root is
      a useful specimen for the diagnosis of acute PCP poisoning because PCP, PCHP and
      t-PCPdiol are detected very soon after administration and a large amount of them
      is retained in hair root for a long time. PCHP was found from the early stage in
      hair roots and its concentration was higher than that of t-PCPdiol for 6 h.
      However, the concentration of t-PCPdiol became higher than that of PCHP after 6
      h. These phenomena could be explained by the time lag of production of the
      primary (PCHP) and the secondary metabolite (PCPdiol).

PMID- 9631501
TI  - Formulation and characterisation of a buccoadhesive erodible tablet for the
      treatment of oral lesions.
AB  - Buccoadhesive erodible tablets of trimcinolone acetonide were prepared using
      different bioadhesive polymers along with excipients like mannitol and PEG-6000.
      In vitro release characteristics were evaluated using a 'flow-thru assembly'
      which simulated the conditions of the human buccal cavity. The bioadhesive
      performance and the surface pH of the tablets was satisfactory. The optimized
      formulation containing 8.0 mg of triamcinolone acetonide, 2.5 mg of mannitol, 7.5
      mg of PEG-6000, 2.0 mg of magnesium stearate along with carbopol-934P (CP-934P)
      and sodium carboxy methyl cellulose-DVP (SCMC-DVP) in the ratio of 1:4 was found
      to release the drug for a period of over 8 h without getting dislodged. Maximum
      in vitro drug release was found to be 79.08% in 8 h study. In vivo evaluation of
      placebo buccoadhesive tablets revealed adequate comfort, taste, non-irritancy
      during the period of study. None of the volunteers reported severe dry
      mouth/severe salivation or heaviness at the place of attachment. A linear and
      positive correlation was found between in vitro and in vivo mean adhesion time.
      The buccoadhesive tablet eroded completely after 8 h leaving no exhausted device
      to be removed. This formulation has potential clinical usefulness for the
      treatment of oral lesions.

PMID- 9631502
TI  - Iontophoretic transdermal delivery of salbutamol: methyl-orange ion-pair.
AB  - The influence of pulsed current duty cycle, addition of electrically neutral
      species and pH on iontophoretic transdermal delivery of an organic ion-pair
      salbutamol:methyl orange through excised rabbit abdominal skin is described. It
      was compared with salbutamol sulphate and salbutamol:sulphate ion-pair. It was
      found that there exists an optimum duty cycle range (1:3-1:4) at which
      iontophoretic flux of the ion-pair was at a maximum because of partition-electric
      current synchronization. Addition of mannitol decreases the flux of the ion-pair
      showing the important role of electroosmosis in ion-pair transport. The extremes
      of pH decrease the flux rates.

PMID- 9631503
TI  - Anthranoid free radicals found in pseudomelanosis coli.
AB  - Pseudomelanosis coli occurs after prolonged intake a anthranoids. After
      discontinuation of intake the pigmentation disappears apparently without noxious
      effects, including carcinogenicity and genotoxicity. We are presenting ESR
      spectra of pseudomelanosis coli specimen, compared to ESR spectra of pigmented
      skin scales taken from psoriatic patients treated topically with anthralin, and
      with ESR spectra of anthralin brown material formed in vitro. The ESR spectra
      show comparable g values within the accuracy of measurements. The examined
      specimens reveal remarkable stability: the intensity of the ESR signal remained
      practically constant over the period of four years. The chemical and
      physicochemical properties of the brown pigments formed from anthranoids explain
      the observed bio-inertness of these materials including that of melanosis coli
      pigment derived from anthranoids.

PMID- 9631504
TI  - [Kastner and Trommsdorff].
AB  - The aim of this paper is to demonstrate the connection between Karl Wilhelm
      Gottlob Kastner (1783-1857) and Johann Bartholomaus Trommsdorff (1770-1837).
      Kastner was the teacher of Justus Liebig (1803-1873) in Bonn and Erlangen. The
      correspondence, which includes unpublished letters from Kastner to Trommsdorff,
      presents a wealth of detailed information for the biographies of Kastner and
      Trommsdorff.

PMID- 9631505
TI  - Synthesis of novel pyrazole derivatives of pharmaceutical interest.

PMID- 9631506
TI  - Triiodothyronine uptake by the isolated rat heart.

PMID- 9631507
TI  - Expression of maize gamma zein C-terminus in Escherichia coli.
AB  - Prolamins containing a highly conserved cysteine-rich C-terminal domain have been
      poorly expressed as soluble protein in model systems such as Escherichia coli.
      Possible reasons have included a combination of the reducing environment of the
      bacterial cytoplasm and protein secondary structure. Using a bacterial
      thioredoxin fusion expression system, full-length native gamma zein, native gamma
      zein C-terminus, and modified gamma zein C-terminus, containing 13 amino acid
      changes, were found to accumulate up to 58, 50, and 42% of the total cellular
      protein, respectively. The native gamma zein C-terminus fusion protein was six
      times more soluble (70%) than the full-length fusion protein (12%), four times
      more soluble than the N-terminus (19%), and eight times more soluble than the
      modified C-terminus (9%). The modified C-terminal domain contained amino acid
      changes that improved the lysine, isoleucine, and tryptophan content, while
      removing two evolutionarily conserved cysteines and one nonconserved cysteine.
      Expression of the native C-terminal domain without thioredoxin resulted in
      decreased solubility (13%) and decreased expression (8%). In contrast,
      coexpression with thioredoxin resulted in a sevenfold increase in solubility
      (86%). These results suggest that insolubility of full-length gamma zein results
      from structural interactions of the N-terminus and that solubility of the C
      terminal domain is dependent on proper disulfide bond formation. The ability to
      express the C-terminal domain of gamma zein as soluble protein should allow
      future identification of important structural elements in gamma zein and similar
      proteins.

PMID- 9631508
TI  - Expression and purification of the human thrombin receptor.
AB  - The human thrombin receptor has been overexpressed in Sf9 (Spodoptera frugiperda)
      insect cells using a baculovirus vector. Cell surface expression of the receptor
      was confirmed by immunocytochemistry with polyclonal antibodies raised against
      the extracellular domain of the receptor. The expressed receptor was functional;
      both thrombin and the thrombin receptor agonist peptide produced increases in
      intracellular calcium in transfected cells. The concentration of thrombin causing
      the half-maximal increase (EC50) in intracellular calcium was 3.9 nM, whereas the
      EC50 for the agonist peptide was 2.7 microM. However, the observed maximum
      increase in intracellular calcium concentration with the agonist peptide (547 nM)
      was twofold greater than that observed with thrombin (258 nM). The recombinant
      receptor was purified by immunoaffinity chromatography using a monoclonal
      antibody raised against the receptor extracellular domain. The purified
      preparation contained two species with apparent molecular masses of 48 and 90
      kDa, both of which were recognized by mono- and polyclonal antibodies against the
      thrombin receptor. The yield of the purified receptor was 0.78 mg/liter of insect
      cells suspension culture (10(6) cells/ml). The purified thrombin receptor will be
      useful in future structural and functional studies.

PMID- 9631509
TI  - Reconstitution and purification of eukaryotic initiation factor 2B (eIF2B)
      expressed in Sf21 insect cells.
AB  - Eukaryotic initiation factor eIF2B plays a key role in the regulation of protein
      synthesis through its ability to catalyze the exchange of GDP bound to a second
      initiation factor, eIF2, for free GTP. In contrast to other GDP-GTP exchange
      factors (GEFs), which are often single subunit proteins, eIF2B consists of five
      dissimilar subunits. In the studies reported here the baculovirus expression
      vector system (BEVS) was used to express FLAG epitope tagged alleles for the
      alpha, beta, gamma, delta, and epsilon subunits of rat eIF2B in Sf21 cells. The
      eIF2B holoprotein was reconstituted in vivo by coexpression of all five subunits
      in Sf21 cells and was subsequently purified to greater than 98% homogeneity using
      a two-step procedure involving an anti-FLAG immunoaffinity column followed by gel
      filtration chromatography. The purified five-subunit eIF2B complex had high GEF
      activity as assayed by using [3H]GDP-bound to eIF2 as a substrate. Alternatively,
      eIF2B with high GEF activity was reconstituted in vitro by mixing crude cell
      lysates containing different eIF2B subunits. The latter results suggest that
      eIF2B activity in vivo could involve alterations in the concentration and/or the
      availability of individual subunits for holoprotein assembly. Overall, the
      results show the utility of the baculovirus-insect cell system for the
      expression, assembly, and purification of active recombinant multisubunit
      factors.

PMID- 9631510
TI  - Large-scale preparation, purification, and crystallization of UDP-N
      acetylmuramoyl-L-alanine: D-glutamate ligase from Escherichia coli.
AB  - The UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase from Escherichia coli, an
      enzyme involved in the biosynthesis of the bacterial peptidoglycan monomer unit,
      was overproduced and purified to homogeneity on a large scale, yielding 4 mg of
      protein per liter of bacterial culture. Crystals of the complex with the
      substrate UDP-MurNAc-L-Ala were grown by the hanging drop method using ammonium
      sulfate as the precipitant. They are tetragonal with cell dimensions a = b = 65.5
      A and c = 134.59 A, space group P4(1) or P4(3), and contain one monomer of 46,842
      Da in the asymmetric unit. In order to use the multiple-wavelength anomalous
      diffraction method for phasing, a selenomethionine derivative of the protein has
      also been overproduced, purified, and crystallized.

PMID- 9631512
TI  - Human pancreatic triglyceride lipase expressed in yeast cells: purification and
      characterization.
AB  - A cDNA clone encoding human pancreatic triglyceride lipase was cloned into a
      yeast expression vector so that the yeast PHO1 signal peptide replaced the native
      signal peptide. Pichia pastoris cells were transfected with the vector, and
      clones expressing human pancreatic triglyceride lipase were isolated. Recombinant
      human pancreatic lipase was expressed in broth cultures and was purified from the
      medium by DEAE blue Sepharose and hydroxyapatite chromatography. The highly
      purified lipase had specific activities for various triglyceride substrates
      identical to those of tissue-purified human pancreatic triglyceride lipase; it
      was inhibited by bile salts, required colipase for activity, and demonstrated
      interfacial activation. This expression system is suitable for the rapid,
      efficient production of human pancreatic triglyceride lipase in amounts adequate
      for biophysical studies.

PMID- 9631511
TI  - Purification and characterization of human procolipase expressed in yeast cells.
AB  - We report the successful, efficient, and large-scale expression of recombinant
      human procolipase in yeast. Using the full-length cDNA of human procolipase,
      constructs were made using either the native human procolipase signal peptide
      sequence or the signal peptide sequence of yeast. These constructs were used to
      transform yeast cells, and expression was followed. Only minimal expression was
      seen with the procolipase using the native human signal peptide. Robust secretion
      of the procolipase occurred when the yeast signal peptide was exchanged for the
      native signal peptide. Expression yielded more than 30 mg/liter. The recombinant
      protein was purified from the medium by immunoaffinity chromatography. The highly
      purified procolipase was free of proteolytic degradation and displayed activity
      and binding characteristics that were indistinguishable from those of tissue
      purified human pancreatic colipase. Expression in yeast cells provides a useful
      tool for expressing intact, unprocessed recombinant wild-type and mutated
      procolipase.

PMID- 9631513
TI  - Purification of NADPH-free glutathione disulfide reductase from human
      erythrocytes.
AB  - Human erythrocyte glutathione disulfide reductase was purified using serially
      connected 2',5'-ADP-Sepharose 4B affinity and anion-exchange columns. About
      11,000-fold purification was achieved with 90% yield. The specific activity of
      the final preparation was 140 units per milligram of protein. The purified enzyme
      gave a single band on both native and SDS-PAGE with a subunit mass of 58 kDa. Its
      pH optimum was 7.20. The Michaelis constants determined at pH 7.4, 37 degrees C,
      fell within the range of previously reported values [K(m)(NADPH) = 18 microM, at
      30-200 microM NADPH; K(m)(GSSG) = 72 microM, at 40-1000 microM glutathione
      disulfide, both at saturating concentrations of the second substrate]. The
      affinity eluent NADPH and its oxidized form NADP+ were successfully removed from
      the enzyme on the ion-exchange column. The purification method developed is very
      useful when the enzyme source material is scarce (e.g., in preparations from
      human tissues) and may find further application in the purification of other
      NAD(P)H-dependent enzymes which might be inactivated by their affinity eluent(s).

PMID- 9631514
TI  - Secretion of biologically active human interleukin-2 and interleukin-4 from
      genetically modified tobacco cells in suspension culture.
AB  - Biologically active human interleukin-2 (IL-2) and IL-4, key lymphokines involved
      in immune regulation, were produced and secreted into the medium by genetically
      modified Nicotiana tabacum cells grown in suspension culture. Secretion through
      the plasma membrane and cell wall into the medium was facilitated by the natural
      mammalian leader sequences. IL-2 and IL-4 were detected in the medium at
      concentrations of 0.10 and 0.18 microgram/mL, respectively, although higher
      levels were detected within the lymphokine-producing cells (approximately 0.80
      microgram/mL for IL-2 and approximately 0.28 microgram/mL for IL-4). By Western
      blot, IL-4 was found to be secreted as two small polypeptides with molecular
      masses of approximately 18-20 kDa. The biological activity of IL-2 was determined
      by cell proliferation of the IL-2-dependent murine CTLL-2 cell line, while that
      of IL-4 was determined by cell proliferation of the CTLL-2 cell line [CT.h4S]
      which was stably transfected with the human IL-4 receptor. These findings
      indicate that plant suspension culture can be used to produce and secrete into
      the medium a variety of biologically active mammalian proteins that are of
      clinical and diagnostic relevance.

PMID- 9631515
TI  - Overexpression, isotopic labeling, and spectral characterization of Enterobacter
      cloacae nitroreductase.
AB  - Bacterial nitroreductases have generated much interest recently due to their
      central roles in both nitroaromatic bioremediation and nitroaromatic toxicity,
      mutagenicity, and carcinogenicity. Enterobacter cloacae nitroreductase (NR) has
      been subcloned into the pET overexpression system and purified to homogeneity via
      a four-step procedure resulting in a final yield of 65.7 mg per liter.
      Overexpression in minimal media containing 15NH4Cl as the sole source of nitrogen
      yielded 37.6 mg per liter of homogenous NR containing > 99 atom % 15N. A series
      of melting curves generated under a variety of solvent conditions established the
      optimal conditions for NR stability as pH 7.5, low ionic strength phosphate
      buffer. A two-dimensional 1H-15N heteronuclear single quantum coherence nuclear
      magnetic resonance spectrum demonstrates this enzyme to be amenable to study by
      high-resolution multidimensional NMR in combination with amino-acid-specific
      isotopic labeling. Optical spectra of the purified enzyme suggest that the
      noncovalently bound flavin mononucleotide cofactor binds in a hydrophobic
      environment and is in the neutral and anionic protonation states in the oxidized
      and two-electron reduced oxidation states, respectively. NR exhibits a novel
      visible region circular dichroism spectrum which has a small distinct negative
      band at 366 nm and a large positive ellipticity at 454 nm with a shoulder
      centered at 480 nm.

PMID- 9631516
TI  - Addition of a poly-(6X) His tag to Milk Bundle-1 and purification using
      immobilized metal-affinity chromatography.
AB  - Milk Bundle 1 (MB-1) is a de novo designed protein enriched in M, T, K, and L.
      Its future application is as a high-quality dietary protein source for ruminants.
      The protein is currently expressed in Escherichia coli and is being characterized
      to solve its folded conformation. MB-1 has marginal stability at room
      temperature, which has hindered our attempts at characterization. To increase the
      stability of the protein at room temperature, the purification procedure was
      examined and changed to hopefully increase its effectiveness. We describe here
      the production and purification of a new MB-1 with six His residues at the C
      terminal end. This allows the new mutant (MB-1-His) to bind metal ions and to be
      purified with immobilized metal-affinity chromatography (IMAC). MB-1-His obtained
      using IMAC was purer on SDS-PAGE than both MB-1 or MB-1-His isolated using the
      current protocol. The IMAC protocol is more economical and more efficient;
      preliminary results show that the protein purified by this method is also quite
      stable at room temperature.

PMID- 9631517
TI  - Presence of an N-terminal polyhistidine tag facilitates stable expression of an
      otherwise unstable N-terminal domain of mouse tissue inhibitor of
      metalloproteinase-1 in Escherichia coli.
AB  - The active N-terminal domain of the mouse tissue inhibitor of metalloproteinases
      1 is a 14.1-kDa polypeptide with three disulfide bonds. When expressed using a T7
      system in Escherichia coli, this truncated protein, in contrast to the WT
      protein, was found only in trace amounts in the cell. However, when the coding
      sequence was placed downstream of a 60-bp sequence that encoded an in-frame
      histidine-rich "tag," the fusion product (NF.TIMP*His) was expressed in
      considerably increased abundance. WT.TIMP-1 was expressed in abundance with or
      without the tag. The mRNAs encoding the various forms of TIMP were present in
      similar amounts in all four cases. NF.TIMP*His, renatured and purified on a
      nickel affinity column, was found to be about 10-fold less effective than native
      human TIMP-2 at inhibiting cleavage of collagen type I by human fibroblast
      collagenase. A thrombin cleavage site in the tag was susceptible to cleavage by
      low levels of a contaminating proteinase.

PMID- 9631518
TI  - High-level secretion of a wheat lipid transfer protein in Pichia pastoris.
AB  - Plant nonspecific lipid transfer proteins are small basic proteins with eight
      cysteine residues, all engaged in disulfide bonds. The sequence encoding the
      wheat 9-kDa LTP was cloned into the secretion vector pYAM7SP8 giving rise to
      pYTdltp4.90. Production in shake-flasks and a fermentor led to the synthesis of
      two major species of LTP: a larger than expected species of 14 kDa and a species
      of 10 kDa, close to the expected size of wheat LTP. When production was carried
      out in a fermentor with regulation of pH, oxygen level, and feed rate of carbon
      source, the 10-kDa species was the main protein at the end-point of culture. The
      recombinant wheat LTP (rLTP), secreted at a level of 720 mg/liter into the
      culture medium, is soluble. The rLTP was purified to homogeneity by ammonium
      sulfate precipitation, gel filtration, and anion-exchange chromatography, with a
      recovery yield of 36%. However, the molecular mass of rLTP, determined by mass
      spectrometry, is 9996 Da, while its naturally occurring counterpart has a
      molecular mass of 9607 Da. This discrepancy in size corresponds to a protein
      carrying three extra amino acids (DKR) at its N-terminal end, and this was
      confirmed by sequencing. In vitro lipid transfer activity showed that rLTP
      behaves in a similar way to the naturally occurring protein. These data indicate
      that Pichia pastoris is an efficient system for production of large quantities of
      soluble and biologically active rLTP for structure/function analysis.

PMID- 9631519
TI  - Expression and purification of Streptococcus pneumoniae hyaluronate lyase from
      Escherichia coli.
AB  - Pneumococcal hyaluronate lyase enzyme breaks down hyaluronan of the extracellular
      matrix of tissues and possibly contributes to the invasion of host tissue and to
      the penetration of host defenses by this bacterial pathogen. In light of the
      emergence of increasing numbers of antibiotic-resistant strains, the
      understanding of the mechanism of action of hyaluronate lyase enzyme may lead to
      a better understanding of interactions between a host and bacterial pathogens and
      may contribute to more efficient treatment of bacterial infections. The native
      Streptococcus pneumoniae hyaluronate lyase enzyme has a molecular mass of 107 kDa
      but undergoes conversion to smaller enzymatically active forms. The truncated 83
      kDa functional form of the enzyme has been cloned into the pET-21d vector,
      expressed in Escherichia coli, and purified to homogeneity using a nickel
      affinity column with chelating Sepharose fast flow media. The recombinant enzyme
      is active and stable and the availability of large quantities of the enzyme will
      help in its biochemical and biophysical characterization. As a number of other
      Gram-positive surface proteins, it appears that the enzyme is anchored via its
      carboxy-terminal part to the pneumococcal cell wall by a covalent linkage with
      peptidoglycan structures.

PMID- 9631520
TI  - Overproduction, in Escherichia coli, of soluble taxadiene synthase, a key enzyme
      in the Taxol biosynthetic pathway.
AB  - Taxadiene synthase catalyzes the conversion of the universal precursor of
      diterpenoids, geranylgeranyl diphosphate, to taxadiene, a key intermediate in
      Taxol (paclitaxel) biosynthesis. The gene encoding taxadiene synthase was cloned
      recently. Here we report a method for the heterologous overexpression of cDNA
      encoding taxadiene synthase in Escherichia coli using a thioredoxin fusion
      expression system, which increases the solubility of expressed protein. Taxadiene
      synthase cDNA was amplified by polymerase chain reaction and then subcloned into
      pET3d and pET32a(+) to form pET3dTX and pET32TX, respectively. The expressed
      taxadiene synthase from E. coli BL21(DE3)/pET3dTX was present completely as
      inclusion bodies. The transformant E. coli BL21(DE3)/pET32TX produced a
      thioredoxin fusion taxadiene synthase (15-20% of total soluble protein) when
      induced with isopropyl beta-D-thiogalactopyranoside at low temperature (20
      degrees C). The recombinant enzyme was purified by a single step with a His
      binding metal affinity column. The maximal production attained was 13 mg of
      purified, active fusion protein per 500 ml culture of E. coli BL21(DE3)/pET32TX.
      The purified recombinant taxadiene synthase fusion protein was similar to native
      protein in steady-state kinetic parameters and mobility on sodium sulfate
      polyacrylamide gel electrophoresis. The protein purified from E. coli
      BL21(DE3)/pET3dTX had the expected N-terminal (AQLSFNA) sequence.

PMID- 9631521
TI  - Expression of sunflower homeodomain containing proteins in Escherichia coli:
      purification and functional studies.
AB  - Complementary DNA sequences encoding different portions of two sunflower
      homeodomain proteins were cloned in-frame in the expression vectors pRSET and
      pGEX-3X. When introduced into competent Escherichia coli cells and induced, the
      resulting plasmids directed the expression of large amounts (5-10% of total
      cellular protein) of the encoded polypeptides. As a rule, fusions in pRSET
      rendered insoluble proteins, while fusions in pGEX were soluble and could be
      purified in a single step by selective absorption onto glutathione-agarose beads,
      followed by elution with free glutathione. The purified proteins showed both
      glutathione S-transferase and DNA-binding activity, indicating that they retain
      their native conformation. The expression-purification protocol that was employed
      allowed the isolation of up to 0.7 mg of protein per gram of transformed cells.
      One of the fusion proteins, RH11 (which is a fusion of the homeodomain protein
      HAHR1 in pRSET), though insoluble, was able to bind DNA when spotted onto a
      nitrocellulose filter. This protein could also be simply purified in large
      amounts by electroelution from sodium dodecyl sulfate-polyacrylamide gels and
      used to elicit antibodies which recognized both the transgenic fusion and the
      native protein from sunflower nuclei. Our results clearly show that vector choice
      is a critical parameter for obtaining large amounts of a desired protein for
      particular purposes.

PMID- 9631522
TI  - Expression and purification of correctly processed, active human TACE catalytic
      domain in Saccharomyces cerevisiae.
AB  - Human tumor necrosis factor-alpha (TNF alpha) converting enzyme (TACE) releases
      soluble TNF alpha from cells. It is a member of the adamalysin family of
      metalloproteases. A truncated form of TACE cDNA was expressed in Saccharomyces
      cerevisiae and purified to homogeneity in order to study TACE structure and
      function. Recombinant TACE was expressed as a preproprotein including the pro-
      and catalytic (PROCAT) domains fused to the yeast alpha-factor leader. A C
      terminal immunoreactive FLAG peptide was added for Western blot detection and
      anti-FLAG antibody column purification. We constructed two glycosylation mutant
      PROCAT TACE isoforms to facilitate purification. A PROCAT isoform, mutated to
      eliminate two N-linked glycosylation sites, was buffer exchanged and purified to
      homogeneity by ion exchange chromatography and an anti-FLAG antibody affinity
      step. N-terminal sequence analysis showed that the mutant preproprotein was
      processed in yeast at the furin protease cleavage site and yielded an active
      catalytic domain which has TNF alpha peptide-specific protease activity. Mass
      spectrometry of the purified catalytic domain showed that removal of both N
      linked sites results in a homogeneous sized polypeptide lacking further
      posttranslational modifications.

PMID- 9631523
TI  - The human D1A dopamine receptor: heterologous expression in Saccharomyces
      cerevisiae and purification of the functional receptor.
AB  - Functional human D1A dopamine receptor has been expressed in Saccharomyces
      cerevisiae. The primary sequence of the receptor was modified to include two
      affinity tags at the C-terminus of the protein, a FLAG tag (DYKDDDDK), and a His6
      tag (HHHHHH). These modifications allowed for purification to near homogeneity
      using immobilized metal affinity chromatography and immunoaffinity
      chromatography. Radioligand binding demonstrated that the purified and
      reconstituted receptor binds the antagonist [3H]SCH23390 with an affinity (KD =
      8.0 +/- 3.2 nM) comparable to that of the native receptor.

PMID- 9631524
TI  - Purification and biochemical properties of soluble recombinant human Bax.
AB  - Bax is a member of the Bcl-2 protein family with proapoptotic properties. The
      proteins of this family contain three highly conserved regions termed BH1, BH2,
      and BH3 as well as a hydrophobic COOH-terminal domain, which is responsible for
      the membrane attachment of the proteins. We have expressed human Bax truncated of
      the 20 amino acid COOH-terminal hydrophobic domain to obtain large amounts of
      soluble protein suitable for biochemical and structural studies. The truncated
      protein was expressed as a glutathione S-transferase (GST) fusion protein in
      Escherichia coli. The GST-Bax fusion protein was bound to glutathione-Sepharose,
      and Bax was released by thrombin cleavage and further purified by sequential
      chromatography on heparin-Sepharose and DEAE-Sepharose. The purified protein was
      present in solution as a heptamer and multimers of the heptamer complex. Limited
      tryptic digestion cleaved the protein in the region preceding the BH3 domain and
      produced a specific stable protein fragment of 15 kDa. Phosphorylation has been
      proposed as a possible regulatory mechanism of the bcl-2 proteins. The Bax
      protein was an in vitro substrate for specific serine/threonine protein kinases.

PMID- 9631525
TI  - Production of human lactoferrin in transgenic tobacco plants.
AB  - Production and characterization of human lactoferrin (hLf) in transgenic tobacco
      is reported. We have engineered two constructs containing either the native
      signal peptide from human lactoferrin or the signal peptide from sweet potato
      sporamin fused to human lactoferrin encoding cDNA. N-terminal sequences of rhLf
      purified from tobacco were identical to Lf from human milk for both constructs.
      The tobacco rhLf presents a molecular mass closely identical to native protein.
      Overall sugar composition shows the presence of plant specific xylose while
      sialic acid is absent. Binding parameters of the recombinant molecule to both
      Jurkat lymphoblastic T-cells or HT29-18-C1 enterocytes are similar to those of
      human lactoferrin isolated from milk.

PMID- 9631526
TI  - Production of human tissue factor using the Pichia pastoris expression system.
AB  - Tissue factor plays an important role in the initiation of the blood coagulation
      cascade resulting in the formation of a fibrin clot. The extracellular domain of
      human tissue factor has been expressed in the protease-deficient strain of the
      methylotrophic yeast Pichia pastoris, SMD1168. Tissue factor was expressed with a
      human influenza hemagglutinin tag fused at the C-terminus under control of the
      regulatory sequences from the Pichia AOX1 gene. Expressed protein was secreted in
      a soluble form at levels of up to 10 mg L-1 and correct processing of the PHO1
      signal sequence was confirmed by N-terminal amino acid sequence analysis. Tissue
      factor was produced in Pichia as three discrete forms which appeared as three
      bands in the range 37-45 kDa by SDS-PAGE. These were all recognized by an anti
      tissue factor monoclonal antibody. Deglycosylation studies using Endo H showed
      that the three forms were the result of differences in glycosylation of the
      protein. The low levels of secreted proteins produced by P. pastoris make this an
      efficient host for producing biologically active recombinant tissue factor
      requiring little purification.

PMID- 9631527
TI  - A comparative study of serological tests for use in the bovine herpesvirus 1
      eradication programme in The Netherlands.
AB  - We compared a gB-ELISA, a gE-ELISA and a Danish test system (consisting of a
      blocking and an indirect ELISA) for their specificity and sensitivity to detect
      antibodies against BHV1. The Danish test system showed the highest sensitivity
      and the gE-ELISA the lowest; the gB-ELISA showed an intermediate sensitivity. If
      the doubtful zone (25-50% blocking) of the gB-ELISA was considered as positive
      (gB-ELISA+), the sensitivity almost reached that of the Danish test system. The
      specificity of all tests appeared to be very high, 99.7, 96.7, 100, 99.7% for the
      gB-ELISA, gB-ELISA+, gE-ELISA and the Danish test system, respectively.
      Seroconversion was detected in the gE-ELISA up to 3 weeks later than in the gB
      ELISA and the Danish test system. It is concluded that the combination of a gB
      ELISA (for screening) and the Danish test (for confirmation) system used in the
      BHV1 eradication programme in the Netherlands, provides for very high sensitivity
      (> 99.0%) (Kramps et al., 1994) and a very high specificity (> 99.9%).

PMID- 9631528
TI  - Persistent bovine pestivirus infection localized in the testes of an immuno
      competent, non-viraemic bull.
AB  - A post-pubertal bull on an artificial insemination station was found to be
      persistently shedding bovine viral diarrhoea virus (BVDV) in semen over a period
      of eleven months, while demonstrating no viraemia. Circulating antibodies to BVDV
      were consistently high, suggesting that the immune system was challenged
      repeatedly. Post-mortem findings confirmed that the virus was sequestered in the
      testes of the bull. It is hypothesized that the BVDV in this immuno-competent
      bull was protected from the bull's immune response by the blood-testes barrier.
      The barrier becomes functional only at puberty when tight junctions form between
      adjacent Sertoli cells, suggesting that this bull became persistently infected
      with BVDV during puberty.

PMID- 9631529
TI  - Persistently infected cattle stabilise bovine viral diarrhea virus leading to
      herd specific strains.
AB  - Animals persistently infected with BVDV are important in the epizootiology of the
      Bovine Viral Diarrhea (BVD) because they are a permanent source of contamination
      within a herd. These animals produce large quantities of virus and have,
      therefore, been proposed as responsible for generating antigenic variability.
      However, limited studies have failed to detect antigenic or genetic changes in
      viruses isolated at different time from persistently infected animals. One
      hypothesis to account for this stability is that the immunotolerance is
      accompanied by a selection against antigenic change. The presence of an
      immunotolerant persistently infected (IPI) animal in a herd would in turn lead to
      herd specific strains. To verify this hypothesis, we compared 17 BVDV strains
      isolated from IPI animals from 3 herds of Eastern Belgium. The comparison was
      based on the sequence of a 389 bp fragment of E2--a gene encoding for a highly
      variable glycoprotein. Sequences were strongly conserved within herds but were
      quite different between herds, indicating that BVDV herd-specific strains do
      exist and are associated with the presence of IPI animals.

PMID- 9631530
TI  - An outbreak of infectious hepatitis in commercially reared ostriches associated
      with Campylobacter coli and Campylobacter jejuni.
AB  - A disease causing high morbidity and mortality was observed in young ostriches
      from six properties in southeast Queensland, Australia. The disease affected
      birds from 2-8 weeks of age and was characterised clinically by bright-green
      urates and pathologically by severe necrotic hepatitis. The liver lesions
      resembled those of vibrionic hepatitis in other avian species. Campylobacter coli
      was isolated from the livers of affected ostriches from five of the six
      properties. Campylobacter jejuni subsp. jejuni was isolated from birds from the
      remaining property. Pulsed-field gel electrophoresis-based (PFGE) typing of
      representative isolates indicated that trade of infected birds between farms was
      an important factor in the spread of C. coli. Phenotypic and genotypic data
      suggest a clonal variant of the principal outbreak type may account for the
      remaining cases from which C. coli was found. Conventional biochemical test
      results and PFGE clearly distinguished the C. jejuni strain isolated from the
      geographically remote farm from the outbreak of C. coli type. We believe this to
      be the first definitive report of avian hepatitis associated with C. coli.

PMID- 9631531
TI  - Attachment of different Escherichia coli strains to cultured rumen epithelial
      cells.
AB  - The attachment to fully characterized primary rumen epithelial cell cultures of
      Escherichia coli strains isolated from different animal species and expressing F1
      F4 or F17 fimbriae was examined. As the cell cultures contained stratified
      (keratinized) and non-stratified (non-keratinized) cells which grew either
      confluently or non-confluently, the strength of attachment of the different
      bacterial strains was assessed in relation to the differentiation state of the
      cells. Thus, strains having F1 fimbriae attached to all types of cultured cells,
      while strains with F2 and F3 fimbriae did not bind at all. E. coli strains having
      F4 or F17 fimbriae attached only to non-keratinized cells, particularly to
      confluent areas. As membrane glycosylation is known to change with
      differentiation (keratinization), our results suggest that the attachment of
      fimbriated E. coli strains which were capable of binding to rumen cells was more
      likely to be dependent on differentiation than the host specificity of the
      bacteria.

PMID- 9631532
TI  - Salmonella abortusovis, strain Rv6, a new vaccinal vehicle for small ruminants.
AB  - Salmonella abortusovis strain Rv6 (Sao Rv6) is a live attenuated vaccine used for
      a few years to protect ewes against abortive salmonellosis. As Salmonellae,
      particularly Salmonella aro mutants, have considerable potential as vehicles for
      the presentation of heterologous vaccine antigens, Sao Rv6 was tested in order to
      develop a vaccinal vehicle for small ruminants. Five vector plasmids were tested
      in Sao Rv6; these plasmids, which carry Maltose Binding Protein (MBP) expressed
      as protein, but differ in their promotors, had been previously tested in S.
      typhimurium strain SL3261, and were transferred into Sao Rv6. The five plasmids
      were stable in vitro, and the recombinant Sao Rv6 expressed MBP at various
      levels. Intraperitoneal infection of OF1 mice with the recombinant bacteria did
      not modify the characteristics of Sao Rv6; dissemination and infection levels
      were similar in all groups and all mice developed antibodies to Salmonella
      antigens as measured by ELISA. In contrast, only animals immunized with Sao Rv6
      carrying the pNTE plasmid developed a serum antibody response to MBP. This
      plasmid was then tested in sheep; following subcutaneous immunization with Sao
      Rv6-pNTE, dissemination and infection levels were not modified in comparison with
      sheep immunized with Sao Rv6 lacking plasmid. Antibodies specific to MBP were
      detected in sera of sheep immunized with Sao Rv6-pNTE, purified MBP, and with S.
      typhimurium SL3261-pNTE as positive controls. These results demonstrate that Sao
      Rv6 can be used as a vehicle for heterologous antigens in sheep with pNTE as
      plasmid vector.

PMID- 9631533
TI  - Molecular typing of Salmonella enterica subsp. enterica serovar Hadar: evaluation
      and application of different typing methods.
AB  - A highly discriminatory molecular typing system for isolates of Salmonella
      enterica subsp. enterica (S.) serovar Hadar was developed based on the data
      obtained from 34 epidemiologically unrelated S. Hadar isolates from Germany and
      Brazil. Plasmid profile analysis and macrorestriction analysis with the enzymes
      XbaI, SpeI and BlnI represented the most discriminative typing methods. In
      contrast, ribotyping as performed with a gene probe that recognized the entire
      rrn operon did not reveal any differences between the S. Hadar isolates. IS200
      typing was not applicable due to the lack of insertion elements of this type in
      all S. Hadar isolates included in this study. The combination of the results of
      plasmid analysis and macrorestriction analysis subdivided the 34 S. Hadar
      isolates into 32 different genomic groups. The high discriminatory power of these
      methods confirmed their suitability as effective typing methods for
      epidemiological studies on S. Hadar isolates. The practical application of this
      molecular typing system to S. Hadar isolates of the same flock obtained during a
      15 month period strongly suggested recurring introduction of genomically
      different S. Hadar isolates instead of a single introduction of S. Hadar followed
      by subsequent spread within the flock.

PMID- 9631534
TI  - Serotypes of Escherichia coli isolated from septicaemic chickens in Galicia
      (northwest Spain).
AB  - The purpose of this study was to establish the serogroups of Escherichia coli
      that cause avian colibacillosis in Spain. The serogroups of 625 avian E. coli
      isolated between 1992 and 1993 were determined. The 458 E. coli from chickens
      with septicaemia belonged to 62 different O serogroups; however, 59% were of one
      of 18 serogroups (O1, O2, O5, O8, O12, O14, O15, O18, O20, O53, O78, O81, O83,
      O102, O103, O115, O116 and O132). These 18 serogroups were also determined as an
      important percentage (29%) of control isolates from faeces of healthy birds.
      Nevertheless, a significant difference (59% versus 29%; P < 0.001) was observed.
      Furthermore, the serogroups O12, O14, O18, O53, O78, O81, O102, O115, O116 and
      O132 were almost exclusively identified among septicaemic E. coli (31% versus 3%;
      P < 0.001). The high prevalence of O18, O81, O115, O116 and O132 isolates was not
      expected and may indicate the emergence of five new serogroups associated with
      avian colibacillosis not yet reported.

PMID- 9631535
TI  - Fatty acid binding protein isoforms: structure and function.
AB  - Although structural aspects of cytosolic fatty acid binding proteins (FABPs) in
      mammalian tissues are now well understood, significant advances regarding the
      physiological function(s) of these proteins have been slow in forthcoming. Part
      of the difficulty lies in the complexity of the multigene FABP family with nearly
      twenty identified members. Furthermore, isoelectric focusing and ion exchange
      chromatography operationally resolve many of the mammalian native FABPs into
      putative isoforms. However, a more classical biochemical definition of an
      isoform, i.e. proteins differing by a single amino acid, suggests that the
      operational definition is too broad. Because at least one putative heart H-FABP
      isoform, the mammary derived growth inhibitor, was an artifact (Specht et al.
      (1996) J. Biol. Chem. 271: 1943-49), the ensuing skepticism and confusion cast
      doubt on the existence of FABP isoforms in general. Yet, increasing data suggest
      that several FABPs, e.g. human intestinal I-FABP, bovine and mouse heart H-FABP,
      rabbit myelin P2 protein and bovine liver L-FABP may exist as true isoforms. In
      contrast, the rat liver L-FABP putative isoforms may actually be due either to
      bound ligand, post-translational S-thiolation and/or structural conformers. In
      any case, almost nothing is known regarding possible functions of either the true
      or putative isoforms in vitro or in vivo. The objective of this article is to
      critically evaluate which FABPs form biochemically defined or true isoforms
      versus FABPs that form additional forms, operationally defined as isoforms. In
      addition, recent developments in the molecular basis for FABP true isoform
      formation, the processes leading to additional operationally defined putative
      isoforms and insights into potential function(s) of this unusual aspect of FABP
      heterogeneity will be examined.

PMID- 9631536
TI  - Alternative pathways of anandamide biosynthesis in rat testes.
AB  - We have investigated the biosynthesis of long-chain N-acylethanolamines (NAEs)
      from endogenous substrates in rat testes membranes with special emphasis on
      anandamide (20:4n-6 NAE), a cannabinoid receptor agonist. Incubation of various
      membrane preparations with 5 mM Ca2+ produced both N-acyl
      phosphatidylethanolamine (N-acyl PE) and NAE with primarily (approximately 85%) N
      palmitoyl groups (16:0 NAE) and less than 2% 20:4n-6 NAE. In contrast, incubation
      of these membranes with 5 mM EGTA and 10 mM ethanolamine had little effect on N
      acyl PE composition but yielded NAEs whose major constituent (32-37%) was
      anandamide. Incubations with [1,1,2,2,-2H4]ethanolamine in media containing 40%
      H2(18)O showed that the Ca(2+)-independent NAE synthesis occurred by direct
      condensation of ethanolamine with free fatty acids present in the membrane
      preparation. This biosynthetic activity occurred at ethanolamine concentrations
      as low as 50 microM and exhibited substrate selectivity for arachidonate which
      increased with increasing ethanolamine concentrations. The results of inhibitor
      experiments suggest that the Ca(2+)-independent NAE synthesis was catalyzed by
      the NAE amidohydrolase acting in reverse. This condensation reaction could be
      important in agonist-induced anandamide synthesis for cell signalling through
      cannabinoid receptors.

PMID- 9631537
TI  - Time and temperature dependent aggregation behaviour of the ganglioside GM1 in
      aqueous solution.
AB  - Gangliosides are marked amphiphiles with several ramified sugar rings and a
      ceramide moiety. Therefore they form micelles in aqueous solution. This
      aggregation behavior is studied with static and dynamic light scattering and
      small angle X-ray scattering. The shape and the size of the GM1 micelles in
      dependence of time and temperature are investigated. Some data have been
      published recently where two stable states for the micelles are found. This
      bistability is said to be achieved by temperature rise from room temperature up
      to 55 degrees C. The authors did not find such an internal structural change of
      the micelle in the experiments. Instead the authors found some large aggregates
      of the ganglioside in parallel to the micelle caused by the low solubility of
      this system at room temperature. These aggregates are dissolved quickly with
      increasing temperature or slowly with time at room temperature. So the variation
      of the scattering intensity is explainable by dissolving the large particles,
      meanwhile the structure of the GM1 micelles is the same all the time.

PMID- 9631538
TI  - Cloning and characterization of an accessory gene regulator (agr)-like locus from
      Staphylococcus epidermidis.
AB  - The presence of sequences related to the agr of Staphylococcus aureus was
      demonstrated in Staphylococcus epidermidis by agr-specific PCR, and Southern
      blot. The agr-like locus of S. epidermidis A086 was cloned and sequenced. An
      overall homology of 68% was found between the agr locus from S. epidermidis and
      S. aureus. The agr locus from S. epidermidis was organized similar to those from
      S. aureus and S. lugdunensis. The putative RNAII molecule contains four open
      reading frames, agr A, B, C and D. AgrA was a response regulator. AgrB showed
      homology with transducer and translocase molecules. AgrC is expected to act as a
      histidine protein kinase in which a leucine zipper is present. AgrD is presumably
      processed into an autoinducer peptide. The putative RNAIII molecule contained an
      open reading frame encoding a putative 26 amino acid (aa) polypeptide, which
      differed in 3 aa from the RNAIII encoded delta-toxin of S. aureus. Kinetic
      studies showed that the production of this RNAIII was elevated during the post
      exponential phase. delta-Toxin activity was demonstrated for 21 of 23 tested S.
      epidermidis strains. Kinetic studies of the production of delta-toxin showed that
      the toxin was produced during the post-exponential phase. Sequencing of S.
      epidermidis A097, which showed a delayed agr-response, revealed a truncated AgrC
      lacking the histidine kinase domain. These data indicate that an agr-like locus
      is active in S. epidermidis during the post-exponential phase.

PMID- 9631539
TI  - Constitutive expression of a heterologous Eubacterium ruminantium xylanase gene
      (xynA) in Butyrivibrio fibrisolvens.
AB  - An Eubacterium ruminantium xylanase gene (xynA) was inserted into pYK4, a shuttle
      vector replicable in both Escherichia coli and Butyrivibrio fibrisolvens, and the
      resultant chimeric plasmid (pYK4XT) was electroporated into B. fibrisolvens
      OB156C in an attempt to obtain a more xylanolytic B. fibrisolvens.
      Electrotransformants were screened by the development of erythromycin resistance,
      followed by an activity staining and Southern hybridization. The presence of mRNA
      from xynA in the transformant, B. fibrisolvens NO4, was confirmed by Northern
      hybridization. Xylanase activity of the transformant NO4 was apparently enhanced
      regardless of carbon sources in the medium. When grown on glucose or cellobiose.
      NO4 had approximately 5-6 times higher intracellular activity than the parent
      OB156C on a culture volume basis as well as protein basis. The transformant
      showed extracellular xylanase activity much higher (between 7- and 10(4)-fold)
      than the parent. Transformant NO4 recorded the highest activity when grown on
      xylan. Most (> 90%) of the activity was extracellular. The extracellular activity
      was 2-fold greater in NO4. These findings indicate that the introduced xynA was
      expressed constitutively and the xylanase protein was exported into the culture
      supernatant. Growth of NO4 on glucose was similar to that of OB156C, which
      suggests little extra load for plasmid maintenance and foreign xylanase
      production in the transformant. The plasmid pYK4XT was maintained stably in the
      transformant for more than 100 generations.

PMID- 9631540
TI  - Iron repressibility of siderophore and transferrin-binding protein in
      Staphylococcus aureus.
AB  - In order to investigate whether the iron acquisition mechanisms of Staphylococcus
      aureus are induced by iron restriction in vitro, we examined S. aureus ATCC 6538
      for production of siderophore and expression of transferrin-binding protein (SA
      tbp) in normal or deferrated brain heart infusion broth (BHI). Siderophore
      production was earlier and greater in the deferrated BHI. The SA-tbp, detected by
      ligand blot assay, was expressed only in the deferrated BHI. When human
      transferrin was added to the deferrated BHI, siderophore production was later and
      lower than when transferrin was not present. In conclusion, both iron acquisition
      mechanisms of S. aureus were found to be iron-repressible and via both of them,
      human transferrin-bound iron was utilized for growth under iron-restricted
      condition.

PMID- 9631541
TI  - Determination of the recognition sequence of the type II restriction
      endonuclease, LlaCI, from Lactococcus lactis W15.
AB  - A new type II restriction endonuclease, called LlaCI, was partially purified from
      Lactococcus lactis subsp. cremoris W15. The characterisation of the LlaCI
      endonuclease showed it to be an isoschizomer of HindIII, recognising the sequence
      5-'A decreases AGCTT-3'. The cleavage site is indicated by the arrow.

PMID- 9631542
TI  - Codon usage in Actinobacillus actinomycetemcomitans.
AB  - The codon usage patterns of 21 genes encompassing 5800 codons from Actinobacillus
      actinomycetemcomitans were analyzed. A. actinomycetemcomitans genes could be
      divided into two groups based on their function and G + C content. One group
      included those genes encoding basic cellular functions. This group displayed an
      average G + C content of 48%. A second group comprised genes encoding the
      leukotoxin determinant, an insertion sequence and a plasmid. This group displayed
      an average G + C content of 36%. These findings suggest that portions of the A.
      actinomycetemcomitans genome may have been acquired by horizontal gene transfer
      from one or more distantly related species. We present a table of A.
      actinomycetemcomitans codon usage. These data may be used to establish standards
      for computer programs that predict A. actinomycetemcomitans protein coding
      regions and may be useful in designing degenerate oligonucleotide probes.

PMID- 9631543
TI  - Thermostable alpha-galactosidase from Thermotoga neapolitana: cloning, sequencing
      and expression.
AB  - A gene encoding a thermostable alpha-galactosidase from the hyperthermophile
      Thermotoga neapolitana was cloned and sequenced. Sequence analysis showed that
      the 552-amino acid protein is similar to Escherichia coli Raf type alpha
      galactosidase and belongs to Family 36 of the glycosyl hydrolases. Recombinant
      alpha-galactosidase expressed in E. coli has a molecular mass of ca. 61 kDa, and
      an optimum activity at 93 degrees C at pH 7.0. The enzyme is highly thermostable
      and retains 75% of activity after heating to 80 degrees C for 4 h. The potential
      application of the enzyme to high temperature processing of soy molasses has been
      demonstrated.

PMID- 9631544
TI  - A heat-inducible Bacillus subtilis bacteriophage phi 105 expression system for
      the production of the protective antigen of Bacillus anthracis.
AB  - The protective antigen of Bacillus anthracis is the major protective immunogen in
      the current human vaccine. A heat-inducible protective antigen expression system
      was constructed based on a derivative of Bacillus subtilis phage phi 105. The
      recombinant protein produced by this system protected immunised animals against
      challenge with spores of B. anthracis. Gene instability and protease activity of
      the host strain contributed to the low level of recoverable protein in culture
      supernatant (approximately 2 mg l-1).

PMID- 9631545
TI  - The Staphylococcus qacH gene product: a new member of the SMR family encoding
      multidrug resistance.
AB  - The prevalence of disinfectant-resistant food-related microorganisms is of
      concern to the food industry. The Staphylococcus saprophyticus strain ST2H6
      isolated from a poultry processing plant contained a 2.4-kb plasmid (p2H6)
      harbouring qacH, which encodes resistance to disinfectants based on quaternary
      ammonium compounds. The complete p2H6 nucleotide sequence revealed an open
      reading frame encoding a putative protein of 107 amino acid residues with strong
      similarity to members of the small multidrug resistance protein family. QacH also
      conferred high-level ethidium bromide resistance and low-level proflavine
      resistance and thus differed phenotypically from the similar proteins Smr and
      QacG. Fluorimetry indicated that the high-level ethidium bromide resistance was
      due to improved efflux energised by the proton motive force. Site-directed
      mutagenesis substituting the Asp-24 residue with Glu-24 had no effect on
      resistance characteristics. An additional open reading frame on p2H6 encoded a
      putative protein with similarity to rolling circle replication proteins.

PMID- 9631546
TI  - Serum resistance in bvg-regulated mutants of Bordetella pertussis.
AB  - Serum resistance, or resistance to killing by antibody dependent pathway of
      complement, in Bordetella pertussis is bvg-regulated and the Bordetella
      resistance to killing (brk) locus mediates much of the resistance. Here we
      examined whether other bvg-regulated proteins contribute to serum resistance. We
      found that neither pertussis toxin, adenylate cyclase toxin, filamentous
      hemagglutinin, dermonecrotic toxin, tracheal colonization factor, nor Vag8
      mutants were sensitive to serum killing compared to the wild-type. Filamentous
      hemagglutinin has been reported to bind C4 binding protein, an inhibitor of
      complement, but this activity does not appear to contribute to serum resistance,
      as evidenced by the resistant phenotype of FHA mutants. Clinical isolates were
      serum resistant and wild-type strains possessing an additional copy of the brk
      locus were 2-5-fold more resistant to serum killing.

PMID- 9631547
TI  - Coupling site-directed mutagenesis with high-level expression: large scale
      production of mutant porins from E. coli.
AB  - Combination of an origin repair mutagenesis system with a new mutS host strain
      increased the efficiency of mutagenesis from 46% to 75% mutant clones.
      Overexpression with the T7 expression system afforded large quantities of
      proteins from mutant strains. A series of E. coli BE host strains devoid of major
      outer membrane proteins was constructed, facilitating the purification of mutant
      porins to homogeneity. This allowed preparation of 149 porin mutants in E. coli
      used in detailed explorations of the structure and function of this membrane
      protein to high resolution.

PMID- 9631548
TI  - Zoocin A immunity factor: a femA-like gene found in a group C streptococcus.
AB  - A 6.8-kb fragment of Streptococcus equi subsp. zooepidemicus 4881 DNA containing
      the zoocin A gene (zooA) was cloned in Escherichia coli and sequenced. We have
      identified a gene we call zoocin A immunity factor (zif), which protects the
      producer cell from the otherwise lethal action of its own product. Transformation
      of Streptococcus gordonii DL1 with zooA and zif changed its phenotypic character
      from a non-zoocin A producing-zoocin A sensitive cell to a zoocin A producing
      zoocin A resistant cell. zif has sequence homology to femA (factor essential for
      methicillin resistance) and lif (lysostaphin immunity factor). No differences
      were observed in amino acid or amino sugar compositions of peptidoglycan purified
      from zoocin A sensitive vs. zoocin A immune cells.

PMID- 9631549
TI  - Characterization of the catecholate indicator strain S. typhimurium TA2700 as an
      ent fhuC double mutant.

PMID- 9631550
TI  - Molecular cloning of a light-inducible gene (lipA) encoding a novel pilin from
      Arthrobacter photogonimos.
AB  - Development of pili on cells of Arthrobacter photogonimos is induced by photo
      oxidative conditions. The nucleotide sequence was determined of a light-inducible
      gene (lipA) that encodes the precursor of a light-inducible pilin (designated
      LIP), a polypeptide of 212 amino acids. The N-terminal leader peptide includes a
      typical signal sequence with a consensus cleavage site for signal peptidase 1
      after residue 28, which should generate N-terminal arginine. However, the next
      amino acid, alanine, is the N-terminal residue of the mature protein. The
      abundance of charged amino acids (27% of total), a calculated pI of 9.98, and
      recovery of mostly monomers when cells were washed with 1 M NaCl suggest that
      electrostatic interactions play a dominant role in association of LIP, a novel
      mechanism for assembly of pili.

PMID- 9631551
TI  - Typing of halophilic Archaea and characterization of their cell surface
      carbohydrates by use of lectins.
AB  - Lectins are important tools for cell typing and for the study of cell surface
      components. They have been widely used for the analysis of carbohydrates on the
      surface of many eukaryotic and prokaryotic cells, but they have not yet been
      exploited in the study of the halophilic Archaea (family Halobacteriaceae),
      because of the high salinity required for the structural integrity of these
      microorganisms. We have defined the salt concentration threshold high enough for
      survival of the Archaea, but sufficiently low for lectins to bind to them. Under
      these conditions we studied the interactions of a series of lectins, exhibiting
      different sugar specificities, with diverse halophilic Archaea. Concanavalin A
      was the most reactive by virtue of its glucose (and mannose) binding. The other
      lectins varied in their interactions. The results indicate that lectins might be
      useful probes for both archaeal typing and analysis of their cell surface
      carbohydrates.

PMID- 9631552
TI  - Pheromone-evoked potentials and oscillations in the antennal lobes of the sphinx
      moth Manduca sexta.
AB  - Using intra- and extracellular recording methods, we studied the activity of
      pheromone-responsive projection neurons in the antennal lobe of the moth Manduca
      sexta. Intracellularly recorded responses of neurons to antennal stimulation with
      the pheromone blend characteristically included both inhibitory and excitatory
      stages of various strengths. To observe the activity of larger groups of neurons,
      we recorded responses extracellularly in the macroglomerular complex of the
      antennal lobe. The macroglomerular complex is part of a specialized olfactory
      subsystem and the site of first-order central processing of sex-pheromonal
      information. Odors such as the pheromone blend and host-plant (tobacco) volatiles
      gave rise to evoked potentials that were reproducible upon repeated antennal
      stimulation. Evoked potentials showed overriding high-frequency oscillations when
      the antenna was stimulated with the pheromone blend or with either one of the two
      key pheromone components. The frequency of the oscillations was in the range of
      30-50 Hz. Amplitude and frequency of the oscillations varied during the response
      to pheromonal stimulation. Recording intracellular and extracellular activity
      simultaneously revealed phase-locking of action potentials to potential
      oscillations. The results suggest that the activity of neurons of the
      macroglomerular complex was temporally synchronized, potentially to strengthen
      the pheromone signal and to improve olfactory perception.

PMID- 9631553
TI  - Sound direction modifies the inhibitory as well as the excitatory frequency
      tuning characteristics of single neurons in the frog torus semicircularis
      (inferior colliculus).
AB  - Single-unit recordings were made from the frog inferior colliculus to determine
      whether or not the direction-dependent sharpening of a unit's free-field
      excitatory frequency-threshold curve (FTCe) was accompanied by a broadening of
      its inhibitory frequency-threshold curve (FTCi). To determine the FTCi, a two
      tone-suppression paradigm was employed. The unit's FTCis and FTCes were collected
      at three azimuths: contralateral to the recording site, ipsilateral to the
      recording site, and frontal midline. The result showed that: (1) most inferior
      colliculus neurons (95%) displayed two-tone suppression, (2) the majority (54%)
      of neurons displayed stronger two-tone-suppression leading to broader FTCis when
      the sound was presented from the ipsilateral side than from the contralateral
      side, (3) for some neurons, the borders of the FTCes and FTCis were closely
      aligned, and this juxtaposition persisted at all sound azimuths (namely, when a
      change in sound direction produced a narrowing of a unit's FTCe, its FTCi was
      broadened concomitantly). For the remaining neurons, however, direction-dependent
      sharpening of the FTCe was not accompanied by an increase in two-tone
      suppression. The neural mechanisms that underlie the direction-dependent changes
      in the FTCes and FTCis are discussed.

PMID- 9631554
TI  - Correlation between auditory sensitivity and vocalization in anabantoid fishes.
AB  - Several anabantoid species produce broadband sounds with high-pitched dominant
      frequencies (0.8-2.5 kHz), which contrast with generally low-frequency hearing
      abilities in (perciform) fishes. Utilizing a recently developed auditory
      brainstem response recording-technique, auditory sensitivities of the gouramis
      Trichopsis vittata, T. pumila, Colisa lalia, Macropodus opercularis and
      Trichogaster trichopterus were investigated and compared with the sound
      characteristics of the respective species. All five species exhibited enhanced
      sound-detecting abilities and perceived tone bursts up to 5 kHz, which qualifies
      this group as hearing specialists. All fishes possessed a high-frequency
      sensitivity maximum between 800 Hz and 1500 Hz. Lowest hearing thresholds were
      found in T. trichopterus (76 dB re I microPa at 800 Hz). Dominant frequencies of
      sounds correspond with the best hearing bandwidth in T. vittata (1-2 kHz) and C.
      lalia (0.8-1 kHz). In the smallest species, T. pumila, dominant frequencies of
      acoustic signals (1.5-2.5 kHz) do not match lowest thresholds, which were below
      1.5 kHz. However, of all species studied, T. pumila had best hearing sensitivity
      at frequencies above 2 kHz. The association between high-pitched sounds and
      hearing may be caused by the suprabranchial airbreathing chamber, which, lying
      close to the hearing and sonic organs, enhances both sound perception and
      emission at its resonant frequency.

PMID- 9631555
TI  - Sugar cell responses to lactose and sucrose in labellar and tarsal taste hairs of
      Musca domestica.
AB  - Receptor cell responses in the largest labellar (LL) and tarsal (D) taste hairs
      of the housefly Musca domestica were investigated electrophysiologically using
      the tip-recording technique. In LL hairs, test series with lactose in
      concentrations of 12.5-400 mmol.l-1 yielded a threshold concentration around 12
      mmol.l-1 and a calculated concentration eliciting half-maximal response of around
      40 mmol.l-1, the maximal response varying between 18 and 30 impulses/300 ms. D
      hairs are more sensitive towards lactose, indicated by a slightly lower threshold
      and a by 60% higher response to 400 mmol.l-1 lactose. The high variation in the
      relative stimulating effectiveness of lactose and sucrose and experiments with
      sugar mixtures imply that these sugars bind to different receptor sites without
      noticeable cross affinity. A comparison of the concentration response
      characteristics for sucrose and lactose in LL and D hairs suggests that sucrose
      can combine with more than one site type, expressed in different proportions in
      both hair types. Results obtained with p-nitrophenyl-beta-galactoside as stimulus
      indicate that a beta-galactoside link is not sufficient for a substance to
      interact specifically with the lactose binding site. The exceptional lactose
      sensitivity of the sugar cell in M. domestica is discussed in the context of food
      acquirement and digestion.

PMID- 9631556
TI  - Encoding of acoustic directional information by saccular afferents of the sleeper
      goby, Dormitator latifrons.
AB  - This paper reports on directional response properties of saccular afferents of
      the sleeper goby, Dormitator latifrons, to 100-Hz acoustic particle motions with
      a focus on testing the hypothesis that the response directionality of a fish's
      auditory afferents derives from the morphological polarity of sensory hair cells
      in the otolithic organs. Spontaneous rates (SR) and best sensitivities (BS) of
      saccular afferents ranged from 0 to 162 spikes/sec and from 0.2-to 100-nm RMS
      displacement. SR did not vary with BS. Most saccular afferents were phase-locked
      to sinusoidal stimulation and had sustained temporal response patterns with some
      adaptation. All saccular afferents were directionally sensitive to the stimulus,
      and the sharpness of directional response curves was determined by a
      directionality index (DI). The DI ranged from 0.64 to 1.50 (mean = 1.02, SE =
      0.02, n = 100) and gradually decreased with stimulus level throughout afferents'
      response dynamic range. Many afferents had approximately symmetric directional
      response curves relative to their best response axes (BRA). BRA of most afferents
      remained constant with stimulus level. The BRA distribution had a peak along an
      axis that correlates closely with the morphological polarity of saccular hair
      cells. Therefore, our results strongly support the hypothesis.

PMID- 9631557
TI  - Release of proteins and polysaccharides from the albumen gland of the freshwater
      snail Helisoma duryi: effect of cAMP and brain extracts.
AB  - The albumen gland is a compound tubular exocrine gland found in the female
      reproductive tract of freshwater pulmonate snails such as Helisoma duryi. It
      secretes a perivitelline fluid, composed of protein and polysaccharide complexes,
      and coats each fertilized egg. A 288-kDa native glycoprotein, composed of several
      66-kDa subunits, was identified in soluble extracts of albumen gland. Forskolin
      stimulates the release of secretory granules, containing both proteins and
      polysaccharides, from the cytoplasm of the glandular cells. An acid extract of
      the central nervous system or the adenosine-3', 5'-cyclic monophosphate (cAMP)
      analogue 8-bromo cAMP, stimulates protein secretion from the gland. Pretreatment
      of the albumen gland with cAMP antagonist (Rp isomer of cAMP) inhibits the
      stimulatory effect of a brain extract. Digestion of brain extract with
      proteolytic enzymes abolishes its activity, suggesting the factor from the brain
      is peptidergic. The neuroactive agents serotonin, Phe-Met-Arg-Phe-amide, Tyr-Gly
      Gly-Phe-Met-Arg-Phe-amide, small cardioactive peptide B, and caudodorsal cell
      hormone were also tested for potential secretion-promoting ability. Brain
      extracts were partially purified with a Sep-Pak C18 reverse-phase cartridge and
      indicate the peptide is relatively hydrophobic. These results suggest that a
      brain peptide promotes the secretion of perivitelline fluid, and this is mediated
      by the adenylate cyclase/cAMP signal transduction pathway.

PMID- 9631558
TI  - Epicortical slow potential shifts and sensory-evoked potentials are related to
      seizure propensity in gerbils.
AB  - Gerbils were assessed for behavioral tendency by scoring seizure severity and the
      amount of ambulatory and rearing activities in a novel 'open-field' arena.
      Seizure-prone animals exhibited seizures on early open-field trials (1-2) and
      later performed more ambulatory activity than non-seizure-prone animals. Two
      weeks later, two groups of both seizure prone and non-seizure prone animals were
      chronically implanted with six silver/silver chloride ball electrodes for
      recordings during behaviour. Electrodes were on the surfaces of the frontal,
      parietal and occipital cortices bilaterally. In one group these were used to
      record slow potential shifts; in the other, visual- and acoustic-evoked
      responses. Larger negative and positive slow shifts occurred in seizure-prone
      animals. Most evident were the larger positive right frontal shifts and negative
      left occipital shifts. Seizure tendency was related to the amplitude of these
      waveforms. Visual-evoked potential amplitudes were generally larger and latencies
      shorter in seizure-prone animals, especially in the right occipital and left
      parietal cortices. Seizure susceptibility was associated with increased visual
      evoked potential amplitude in the right frontal and left occipital cortices, and
      with reduced latency of both auditory- and visual-evoked responses in the left
      occipital cortex. The discussion highlights a role for glia in slow shift
      generation and the association of large shifts with enhanced sensory-evoked
      responses, especially in seizure-prone animals.

PMID- 9631559
TI  - Large slow potential shifts occur during halothane anaesthesia in gerbils.
AB  - Continuous recordings were made of slow potential shift activity occurring at six
      locations on the surface of the cerebral cortex of seizure-prone and non seizure
      prone gerbils. Measurements were made for 80-s epochs of recordings of frequency,
      maximum and minimum slow shift amplitude and baseline potential of the brain
      during periods of normal inactivity and subsequently during halothane
      anaesthesia. Induction of anaesthesia initially provoked large (millivolt) slow
      (3-4 s) oscillations in all animals, larger in amplitude than any recorded prior
      to anaesthesia. With increasing depth of anaesthesia, all animals also showed a
      reduction in the amplitude of this spontaneous slow potential shift activity. The
      effect was most pronounced in seizure-prone animals, and subsequent to
      anaesthetic-induced behavioural immobility, these animals also showed a regional
      resistance to the depression of spontaneous slow potential shift oscillations.
      Slow potential shift activity during anaesthesia represents ionic fluxes which
      may normally be involved in modulation of neuronal responsiveness. It was
      suggested that glia may be targets for anaesthetics and that seizure
      susceptibility may confer some degree of resistance to the depressant effects of
      such substances.

PMID- 9631561
TI  - Acoustic distinctions in the speech of male psychopaths.
AB  - A key feature of psychopathy is the ability to deceive, manipulate, and con the
      unwary, while seeming to be perfectly sincere. Is this impression of sincerity
      achieved solely through body gestures and facial expression, or is there also
      something different about the voice quality of psychopaths? We analyzed the
      acoustic characteristics of speech in 20 male offenders (10 psychopaths and 10
      nonpsychopaths), assessed with the Psychopathy Checklist--Revised (Hare, 1991).
      We used a computer program developed by Alpert, Merewether, Homel, Martz, and
      Lomask (1986) to measure variations in amplitude and prosody. Results indicated
      that psychopaths spoke more quietly than controls and did not differentiate, in
      voice emphasis, between neutral and affective words. These findings are
      consistent with the developing view that psychopaths are insensitive to the
      emotional connotations of language. In addition, their vocal characteristics may
      be part of a self-presentation mode designed to manipulate and control
      interpersonal interactions.

PMID- 9631560
TI  - On the concept of comparison in mentally retarded and nonretarded children.
AB  - Two adjective pairs in comparative form, more-less and taller-shorter, were
      tested with moderately mentally retarded (MR) and nonretarded children (NR)
      matched on verbal mental age (MA) and socioeconomic status (SES) in a "show" and
      an "act-out" experimental condition. The data indicated that all the main
      effects, the group, the experimental condition, and the unmarked-marked
      relational terms were significant and so were the interactions of the Group x
      Experimental Conditions, Group x Unmarked Versus Marked Relational Terms, and
      Group x Experimental Conditions and Unmarked Versus Marked Relational Terms. A
      logistic regression analysis (LRA) showed that the relational term shorter in the
      act-out condition best predicted classification membership for the subjects in
      either group, suggesting that the MR children were less able to self-regulate
      behavior. The error types, however, mainly observed in the act-out experimental
      condition were the same from a semantic point of view in either group. The effect
      of the unmarked versus marked distinction cannot be considered independent of the
      experimental conditions applied.

PMID- 9631562
TI  - It takes two to tango: understanding and acquiring symmetrical verbs.
AB  - Children's ability to understand symmetrical verbs was investigated, along with
      adults' use of linguistic and visual cues to learn novel symmetrical verbs.
      Symmetrical verbs encode a relationship r between two entities such that X r Y
      entails Y r X. In Experiment 1, sixteen children (mean age 4;8) acted out two
      types of sentences with symmetrical and asymmetrical verbs. Eight adult judges
      viewed videotapes of the children's performance and tried to guess what sentence
      type was being enacted. Judges' performance was predicted (p < .05) by the verb
      type, symmetrical or asymmetrical. In Experiment 2, seventy-two adult subjects
      received visual and linguistic cues to the meanings of novel verbs. Both cue
      types affected subjects' judgments about whether the new verbs were symmetrical
      or asymmetrical (p < .05).

PMID- 9631563
TI  - Preschool children's mastery of the form/content distinction in communicative
      tasks.
AB  - Preschoolers' mastery of the form/content distinction in language and
      communication, along its contingency on the characteristics of particular task
      requirements and test procedures, was investigated in two studies. The
      theoretical concepts "principle of contrast" and "theory of mind" are closely
      related to the studies. A paraphrase task and a referential communication task
      were used. In the paraphrase task, children from 3 to 6 years of age acted as
      "messengers" and judged whether or not a paraphrase of a message was the same as
      what the child had said. The results in Study 1 indicated that children as young
      as 3 years of age recognized this kind of form/content distinction. Fewer
      children, in particular the younger ones, succeeded with the referential
      communication task in Study 1. However, among the 6-year-olds, the two tasks
      showed a tendency to be significantly related. In Study 2, performance decreased
      among children of all ages, but in particular among the youngest children. In
      Study 2, the two form/content tasks were not correlated in any age group. The
      general conclusion is that there is a range of tasks, which may reveal awareness
      of the form/content distinction among young children, and that it is possible to
      construct tasks which would enable young children to pay attention to this
      distinction. Aspects of awareness of the form/content distinction may start to
      develop early during the preschool period, rather than appearing around the
      school start. However, the question of why only some children, and not the
      majority of them, develop this distinction at a very young age is unsettled, as
      well as the consequences of this early development later on at school.

PMID- 9631564
TI  - Evidence for a postnatal doubling of neuron number in the developing human
      cerebral cortex between 15 months and 6 years.
AB  - The generalization of the finding of no postnatal neurogenesis in non-human
      primates to humans may be incorrect because: (1) rhesus macaques belong to a
      superfamily that diverged more than 25 million years ago from the superfamily
      including the genus Homo; (2) the pulse thymidine labeling method, which
      demonstrates DNA synthesis rather than mitosis per se, is less reliable than some
      have assumed. This study examines changes in the number of neurons in a column
      underneath a cortical surface area of 1 mm2, extending through all cortical
      layers (mm2-column) for 35 gyri (representing about 73% of the human cerebral
      cortex) based on the data of J.L. Conel (1939 to 1967). We corrected these data,
      derived from his measures of cortical neuronal packing density, somal breadth and
      height, and cortical layer thickness at postnatal ages 0, 1, 3, 6, 15, 24, 48,
      and 72 months, for shrinkage and stereological errors. In all 35 gyri, neuron
      number/mm2-column: (1) initially declines (mu = 46% decline, sigma = 8%), 95% of
      which is due to surface area expansion (mean age of nadir value = 15.8 months);
      (2) then increases to age 72 months by 70% (mu = 1.7-fold increase, (mu rate =
      1.1% per month). Because of a a concomitant 1.3-fold increase in cortical surface
      from 15 to 72 months, total cortical neuron number increases 2.2-fold. The close
      agreement between neuron number/mm2-column for Conel's age 72-month data to the
      corresponding values reported by others for adult human and primate cortex using
      more modern methods suggests the finding is not an artifact. Neuronal
      proliferative fate-determining factors provide at least four mechanisms for
      increasing cortical neuron number postnatally, with or without DNA synthesis.

PMID- 9631565
TI  - The dynamics of maternal-effect selfish genetic elements.
AB  - Maternal-effect selfish genes such as Medea or Scat act to kill progeny that do
      not bear a copy of the selfish gene present in the mother. Previous models of
      this system allowed for two types of allele, the selfish (killer) type and the
      sensitive (susceptible) wild-type. These models predict that the invasion
      conditions of the selfish allele are quite broad and that if invasion is possible
      a high frequency equilibrium is to be expected. The selfish element is therefore
      predicted to persist. Here a hypothetical third allele that neither kills nor is
      killed (i.e. insensitive) is considered. Such an allele could enter a population
      by recombination, mutation or migration. The incorporation of this third allele
      profoundly affects the dynamics of the system and, under some parameter values,
      it is possible for the spread of the insensitive allele to lead, eventually, to
      the fixation of the wild-type allele (reversible evolution). This is most likely
      if the death of progeny provides no direct benefit to the surviving sibs (i.e. in
      the absence of fitness compensation), as in insects without gregarious broods.
      Under these circumstances the selfish element cannot spread when infinitely rare,
      only after having risen to some finite frequency. A fitness cost to bearing the
      killer allele then causes its loss. However, if fitness compensation is found
      (e.g. in placental mammals) the invasion of the selfish element from an
      infinitely low level is possible for a wide range of costs and both stable
      coexistences of all three alleles and limit cycles of all three are then found.
      It is therefore to be expected that in mammals selfish maternal-effect genes are
      more likely both to spread and to persist than in insects, due to their different
      levels of fitness compensation.

PMID- 9631566
TI  - Contact activation of blood coagulation: trigger properties and hysteresis.
      Kinetic recognition of foreign surfaces upon contact activation of blood
      coagulation: a hypothesis.
AB  - A mathematical model of contact activation of blood coagulation was developed and
      analysed. The model variables are concentrations of factor XIIa, kallikrein and
      activated high-molecular-weight kininogen. Concentrations of active factors were
      shown to depend on the activating signal value in a hysteretic manner. Within a
      range of relatively small signals, two (activated and non-activated) stable
      states coexist (bistability). Signals of the natural environment (surfaces of
      endothelial and blood cells) seem to be in the range of bistability; therefore,
      contact activation that persists for a short time can induce a transition of the
      system to the activated state, and, correspondingly, the formation of a clot. The
      system cannot return to the initial state, which is characterized by low
      activation levels, until the activating signals decrease significantly below
      those present in the circulation.

PMID- 9631567
TI  - Mafia behaviour and the evolution of facultative virulence.
AB  - Some organisms enforce "maladaptive" behaviours on others of the same or
      different species by imposing costs in the absence of compliance. Such
      enforcement is used by the enforcer to obtain benefits in the possession of the
      enforced individual. This mechanism is known as mafia behaviour in humans, but
      may be widespread in parasite-host relationships in nature, from the cellular
      level to societies. In this paper we describe the evolution of such mafia
      mechanisms, and we propose a fuzzy logic model where the mafia mechanism is based
      on enforcement of hosts by exponentially increasing the cost of resistance to the
      parasite. The benefits of host resistance can be counteracted by parasite
      virulence, or even a decrease in response to an increment in its resistance. This
      parasite response to the host defence increment can be used for the parasite to
      teach the host that it is better to pay part of its benefits than increase its
      extremely costly defence. This model differs from others because it takes into
      account the evolution of host defence related to the evolution of parasite
      virulence (host-parasite coevolution) and points out an optimum in host defence
      related to the facultative virulence of the parasite. We provide several
      potential examples of facultative virulence depending on the antiparasite
      responses of hosts, and we suggest that this kind of mafia behaviour may be a
      widespread mechanism in biological processes at a number of different levels.

PMID- 9631568
TI  - Re-entrant excitation initiated in models of inhomogeneous atrial tissue.
AB  - We demonstrate that a shift of the vulnerable window caused by tissue
      inhomogeneity can play a role in the generation of re-entrant excitation. The
      Earm-Hilgemann-Noble equations were incorporated into one- and two-dimensional
      inhomogeneous partial differential equation models of atrial tissue.
      Inhomogeneity was produced by a reduction of gNa over part of the medium and the
      vulnerable window for initiating re-entrant activity in homogeneous models
      determined from numerical integrations. Forty percent reduction of gNa produced
      little effect on the width of the vulnerable window, but the onset of the
      vulnerable window was delayed. The delay of the vulnerable window facilitates the
      initiation of re-entry at junctions between tissue with normal and reduced
      excitability, even though there is hardly any change in action potential
      duration.

PMID- 9631569
TI  - A mathematical model for Neanderthal extinction.
AB  - A simple mathematical homogeneous model of competition is used to describe
      Neanderthal extinction in Europe. It considers two interacting species,
      Neanderthals and Early Modern Men, in the same ecological niche. Using
      paleontological data we claim that the parameter of similarity, between both
      species, fluctuates between 0.992 and 0.997. An extension of the model including
      migration (diffusion) is also discussed; nevertheless, extinction of Neanderthal
      seems unavoidable. Numerical analysis of travelling wave solutions (fronts)
      confirms the extinction. The wave-front-velocity is estimated from linear
      analysis and numerical simulations confirm this estimation. We conjecture a
      mathematical formulation for the principle of exclusion between competitive
      interacting species (Gause).

PMID- 9631570
TI  - Intercellular spiral waves of calcium.
AB  - Intercellular calcium waves have been observed in a large number of cell types,
      and are known to result from a variety of stimuli, including mechanical or
      hormonal stimulation. Recently, spiral intercellular waves of calcium have been
      observed in slices of hippocampal tissue. We use an existing model to study the
      properties of spiral intercellular calcium waves. Although intercellular spiral
      waves are well known in the context of cardiac muscle, due to the small value of
      the calcium diffusion coefficient intercellular calcium waves have fundamentally
      different properties. We show that homogenisation techniques give a good estimate
      for the plane wave speed, but do not describe spiral behaviour well. Using an
      expression for the effective diffusion coefficient we estimate the intercellular
      calcium permeability in liver. For the bistable equation, we derive an analytic
      estimate for the value of the intercellular permeability at which wave
      propagation fails. In the calcium wave model, we show numerically that the spiral
      period is first a decreasing, then an increasing, function of the intercellular
      permeability. We hypothesise that this is because the curvature of the spiral
      core is unimportant at low permeability, the period being approximately set
      instead by the speed of a plane wave along a line of coupled cells in one
      dimension.

PMID- 9631571
TI  - Probability of quantal secretion and the mobilization of vesicles at the active
      zones of endplates.
AB  - A vesicle mobilization model is developed for active zones of motor-nerve
      terminals. In the model, vesicles from a storage pool are recruited to an
      available pool where they are docked at the active zone, the latter pool being
      replenished by endocytosis. The predictions of this model are then compared with
      experimental results on these active zones. If a styryl dye (FM1-43) is used to
      stain all of the vesicles at motor-nerve terminals then the stores of vesicles
      associated with different active zones are shown to vary considerably in size.
      Under the assumption that the available pool size is proportional to the storage
      pool size, the mobilization model shows that the extent of destaining of these
      stores during a particular period of stimulation is proportional to the size of
      the storage pool, this size being indicated by the initial staining. This is not
      so under the alternative assumption that the available pool size does not vary
      proportionally with store size. If the two pools are proportional then the number
      of quanta released from the available pool is proportional to the storage pool
      size. Experimental results indicate that there is a linear relationship between
      destaining and staining, as well as between quantal release and staining at
      different sites along motor-nerve terminals, thus favouring the hypothesis that
      available pool size (or the size of the active zone) and store size are
      proportional. Given that there are very different store sizes along the length of
      motor-nerve terminals, this analysis provides further evidence for the non
      uniform probability of quantal secretion at different active zones within a
      single motor-nerve terminal.

PMID- 9631572
TI  - Self-organized criticality in spatial evolutionary game theory.
AB  - Self-organized criticality is an important framework for understanding the
      emergence of scale-free natural phenomena. Cellular automata provide simple
      interesting models in which to study self-organized criticality. We consider the
      dynamics of a new class of cellular automata which are constructed as natural
      spatial extensions of evolutionary game theory. This construction yields a
      discrete one-parameter family of cellular automata. We show that there is a range
      of parameter values for which this system exhibits complex dynamics with long
      range correlations between states in both time and space. In this region the
      dynamics evolve to a self-organized critical state in which structures exist on
      all time and length scales, and the relevant statistical measures have power law
      behaviour.

PMID- 9631573
TI  - The paradoxical dynamics of prion disease latency.
AB  - A salient characteristic of the prion diseases--including Creutzfeldt-Jakob
      disease and bovine spongiform encephalopathy in cattle--is an extended
      asymptomatic incubation period followed by a rapid and often fatal clinical
      phase. We present a kinetic model of progression of infection based upon the
      existence of a bottleneck in the natural protein pathways within the cell. The
      model can reconcile the different time-scales of the pre-clinical and clinical
      phases, and is able to account for the dependency of the duration of the
      incubation period on several important governing factors, including the inoculum
      size, the phenotype of the host, and the phenotype of the pathogenic form of the
      prion protein. Our results suggest that saturation events--first of the rate of
      pathogenic transformation (an auto-catalysis ceiling), and subsequently of the
      bottleneck in the protein pathways--could be fundamental in determining the
      dynamics of infection.

PMID- 9631574
TI  - A structured, minimal parameter model of the central nitrogen metabolism in
      Saccharomyces cerevisiae: the prediction of the behavior of mutants.
AB  - In order to enable future pathway engineering of a complex system, such as the
      nitrogen metabolism in yeast, mathematical modelling tools have to be developed.
      The stoichiometric and biochemical characteristics of the glutamate and glutamine
      nodes (the Central Nitrogen Metabolism, CNM) are qualitatively known.
      Quantitative knowledge about the dynamics of the network lacks and needs to be
      developed for metabolic reprogramming. A model-based-experiment approach is
      proposed in which the development of a model initiates new experiments of which
      the results then improve the model. As a first step in this iterative system
      identification cycle, recent experimental data, both qualitative and
      quantitative, obtained from defined studies on the CNM of the yeast Saccharomyces
      cerevisiae have been translated into an initial mathematical model. The model
      approach is based on a combination of Flux Analysis and simple enzyme kinetics.
      The model is constructed using nonlinear Ordinary Differential Equations and
      regulation of the synthesis and activity of key enzymes of the CNM is included.
      The parameters of the model are estimated with a constrained Least Squares
      algorithm using the steady-state and dynamic pulse data of a glutamine limited
      continuous culture. The resulting model describes a continuous culture of a wild
      type strain correctly and in general the trends of the dynamic behaviour after
      both glutamine and ammonia pulses to this culture are good. Inclusion of
      countercurrent reactions and compartmentation in the model is essential for the
      descriptive quality of the model under dynamic conditions. It is clear that more
      experimental work is needed. The model indicates that the GOGAT/Glutamine
      Synthetase (GS) pathway plays a more important physiological stabilizing role in
      yeast than is generally assumed. New, model-based, experiments have to
      investigate the function of GOGAT, especially under dynamic conditions. Also
      redox cofactors and ATP have to be measured. The resulting model is validated
      with data of similar experiments with a GS-mutant. The quality of the prediction
      of the behaviour of the mutant is comparable to the descriptive property, which
      is a very promising result, taking into account the limited dataset compared to
      the system complexity.

PMID- 9631575
TI  - Coevolutionary chase in two-species systems with applications to mimicry.
AB  - We study a general dynamical model describing coevolution of two haploid
      populations with two alleles at a single locus under weak linear symmetric
      frequency-dependent selection. A novel and more realistic element of our modeling
      approach is that both species are allowed to evolve. We analyse conditions for
      "evolutionary chase" between two phenotypically similar species in which one
      species evolves to decrease its resemblance with the other species while this
      other species evolves to increase its resemblance with the first species. We
      apply our results to a series of simple population genetics models describing
      classical Mullerian and Batesian mimicries as well as intermediate cases. We show
      that one of the most important factors influencing the plausibility of non
      equilibrium dynamics in systems of mimicry is the relationship between the
      strength of between-species and within-species interactions. This indicates that
      this relationship should be the focus of both experimental and theoretical work.
      Our results suggest that systematic studies of frequencies of different mimicry
      morphs through time may be very useful.

PMID- 9631576
TI  - Virus dynamics: the effect of target cell limitation and immune responses on
      virus evolution.
AB  - Earlier models of virus evolution during single infections do not include target
      cell limitation. Here we extend the basic mathematical framework of these
      theories and study the effect of target cell limitation on the evolution of
      antigenic variation, increasing replication rates and increasing virus load. We
      find that target cell limitation provides a selection pressure against antigenic
      diversification, and can therefore provide a limit to diversity. Antigenic
      diversity increases virus load; at the maximum level of antigenic diversity,
      virus load, too, is at a maximum.

PMID- 9631577
TI  - Biological activities and clinical application of M-CSF.
AB  - Macrophage colony-stimulating factor (M-CSF) was found to be a glycoprotein with
      a molecular weight of 85 kDa which stimulated macrophage colony formation of
      mouse bone marrow cells in a semisolid agar culture system in 1978. M-CSF
      stimulates differentiation of progenitor cells to mature monocytes, and prolongs
      the survival of monocytes. It enhances expression of differentiation antigens and
      stimulates chemotactic, phagocytic and the killing activities of monocytes.
      Macrophage CSF also stimulates production of several cytokines such as
      granulocyte-macrophage CSF, granulocyte CSF and interleukin (IL)-6 by priming
      monocytes, and directly stimulates production and secretion of IL-8 and reactive
      nitrogen intermediates. In addition to the stimulation of hematopoiesis, M-CSF
      also stimulates differentiation and proliferation of osteoclast progenitor cells
      and cytotrophoblasts. Proteoglycan type M-CSF, which contains chondroitin sulfate
      chains, was found in 1992. In a large-scale double-blind controlled study on
      acute myeloid leukemia (AML), it has been shown that the administration of M-CSF
      to patients after consolidation chemotherapies shortens the periods of
      neutropenia and thrombopenia after chemotherapy and reduces the incidence and
      shortens the duration of febrile neutropenia, as well as shortening the period
      required to finish three courses of intensive consolidation therapy.

PMID- 9631578
TI  - Hemostatic activation and cardiac events after the 1995 Hanshin-Awaji earthquake.
AB  - Earthquake-induced stress seems to induce rheological deterioration associated
      with high blood pressure, an increase of blood viscosity due to hemoconcentration
      and an increase of the fibrinogen level. These changes lead to prolonged
      endothelial cell injury and accelerate fibrin turnover as the result of a high D
      dimer level. An increase of these acute changes caused by mental and physical
      stress after an earthquake might trigger obstructive thrombus in coronary
      arteries in the elderly.

PMID- 9631579
TI  - Recombinant human erythropoietin for late-onset anemia after allogeneic bone
      marrow transplantation.
AB  - Recombinant human erythropoietin (rHu EPO) has been reported to accelerate early
      erythroid reconstitution after bone marrow transplantation (BMT). We conducted a
      pilot study on rHu EPO for late-onset anemia in 9 patients after allogeneic BMT.
      The patients achieved initial erythropoietic recovery (hemoglobin (Hb) range 9.1
      13.4, mean 10.8 g/dl), but then developed transplant-related anemia (Hb range 6.3
      9.7, mean 8.2 g/dl) more than 50 days after BMT. This type of anemia was related
      to graft-versus-host disease (GVHD), cytomegalovirus infection, and/or impaired
      EPO secretion. The patients received 3,000 or 12,000 U of rHu EPO subcutaneously
      three or seven times weekly. Hb levels increased by more than 2 g/dl in 6 of the
      9 patients, but were unchanged in the 3 patients with severe GVHD. These findings
      suggest that in some cases rHu EPO is effective for the treatment of late-onset
      anemia after BMT.

PMID- 9631580
TI  - Diagnostic and biological significance of sideroblastic erythropoiesis in the
      myelodysplastic syndromes.
AB  - We retrospectively reviewed clinical and hematologic features of nine patients
      with acquired idiopathic sideroblastic anemia (AISA). Seven of them had ringed
      sideroblasts (RS) more than 15% of marrow nucleated cells. RS persisted in the
      marrow even in the remaining two patients who had a relatively low marrow
      erythroblasts despite RS ranging from 1/4 to half of the marrow erythroid series.
      However, RS declined in proportion in another two patients of the nine whose
      disease progressed to refractory anemia with excess of blasts (RAEB), although a
      high proportion of RS reappeared in one patient at the time of relapse following
      allogeneic marrow transplantation. A similar decline of RS concomitant with
      disease progression was also seen in seven additional patients with RAEB or RAEB
      in transformation (RAEB-t) with sideroblastic erythropoiesis. Cytogenetic
      abnormalities, although rare initially, became detectable either at the time of
      disease progression or at the worsening of anemia in AISA. These observations
      suggest that the majority of AISA fall in the category of myelodysplasia, and
      that a progressive decline in RS is part of the natural history of
      myelodysplasia. Closer follow-up of the proportion of RS in patients with AISA is
      warranted to better understand its biologic significance.

PMID- 9631581
TI  - Mature and immature myeloid cells decrease the granulocyte colony-stimulating
      factor level by absorption of granulocyte colony-stimulating factor.
AB  - We studied the effects of polymorphonuclear neutrophils (PMN) and immature
      myeloid cells on the granulocyte colony-stimulating factor (G-CSF) level in vitro
      to better understand the regulatory mechanisms of neutropoiesis. Intact normal
      PMN decreased the G-CSF level after incubation with recombinant human (rh) G-CSF
      in a time- and dose-dependent manner. The percent reduction decreased as the
      concentration of rhG-CSF increased. However, the cell-free PMN-conditioned medium
      (PMN-CM) did not decrease the G-CSF level. The intact PMN also decreased the
      granulocyte-macrophage (GM)-CSF level after culture with rhGM-CSF, but did not
      affect the monocyte (M)-CSF level after culture with rhM-CSF. Normal bone marrow
      (BM) immature neutrophilic cells and G-CSF-dependent acute myeloid leukemic cells
      (OCI/AML la) also decreased the G-CSF level, whereas K-562 cells, which have no
      detectable G-CSF receptors, did not affect it. Phenylarsine oxide (PhAsO), an
      inhibitor of endocytosis of ligand receptor complex, abrogated this decreasing
      effect of intact PMN and OCI/AML la cells. These findings suggest that mature and
      immature myeloid cells negatively regulate neutropoiesis by, at least in part,
      decreasing the G-CSF level probably through receptor-mediated continual
      absorption and metabolism of G-CSF.

PMID- 9631582
TI  - Alterations in the colorectal carcinoma gene and protein in a novel human myeloid
      leukemia cell line with trisomy 18 established from overt leukemia after
      myelodysplastic syndrome.
AB  - A new human myeloid leukemia cell line (OIH-1), with alterations in chromosome 18
      and the deleted in the colorectal carcinoma (DCC) gene and its product, was
      established from the peripheral blood (PB) of a patient with acute myeloblastic
      leukemia (AML) after myelodysplastic syndrome (MDS). Serial cytogenetics showed
      the presence of two clones, one with i(18)(q11) and another with trisomy 18.
      Southern blot analysis of OIH-1 cells with i(18)(q11) showed an extremely reduced
      intensity of 20- and 14-kb EcoRI fragments, suggesting the allelic loss of the
      DCC gene. Immunoprecipitation (IP) analysis by the murine monoclonal antibody
      (MoAb) AF5, specific for the DCC extracellular domain, failed to detect normal
      180-kDa DCC protein, however extra 85-kDa protein was detected. However, Southern
      blot analysis of the latter clone of OIH-1 with trisomy 18 showed normal
      structure of the DCC gene. IP analysis with AF5 or G92-13 (specific for the
      extracellular domain) did not detect the DCC protein, but a 150-kDa protein other
      than the DCC-specific 180-kDa protein was detected with G97-449, specific for the
      cytoplasmic domain of the DCC protein. RT-PCR analysis showed the expression of
      the DCC mRNA in OIH-1 cells carrying each type of chromosome 18 abnormalities.
      These alterations in the DCC gene and protein may contribute to progression of
      malignancy for OIH-1 cells. The OIH-1 cell line may be useful for studying the
      role of the DCC gene in leukemogenesis of MDS or AML.

PMID- 9631583
TI  - Determination of Epstein-Barr virus association with B-cell lymphomas in Japan:
      study of 72 cases--in situ hybridization, polymerase chain reaction,
      immunohistochemical studies.
AB  - The association of Epstein-Barr virus (EBV) with B-cell lymphoma was examined in
      72 human immunodeficiency virus-negative Japanese patients using the polymerase
      chain reaction (PCR) on DNA obtained from formalin-fixed paraffin-embedded
      tissues and an in situ hybridization (ISH) technique. EBV-encoded RNA 1 (EBER-1)
      was detected in 12 of 72 cases (17%); five of 33 cases (15%) of nodal B-cell
      lymphomas and seven of 39 cases (18%) of extranodal B-cell lymphomas. Three cases
      of post-bone marrow transplantation and one case of autoimmune disease (Evans
      syndrome) were included among seven EBER-1 positive extranodal lymphomas. A
      combined study of immunohistochemistry and EBER-1 revealed that some L26 positive
      cells were EBER-1 positive. A DNA band was also observed in 13 of 70 examined
      cases (19%) (four of 33 cases of nodal B-cell lymphomas (12%) and nine of 37
      cases of extranodal B-lymphomas (24%)) in the PCR study using primers to detect
      the Bam HI-W fragment of EBV. In the immunohistochemical study using a monoclonal
      antibody to the latent membrane protein 1 (LMP-1) of the EBV, one of the EBV
      encoded latent gene products, LMP-1, was expressed in six of 34 cases (18%) of
      extranodal B-lymphomas, but none of the cases with nodal B-cell lymphomas were
      shown to be LMP-1 positive. Oncoprotein bcl-2 was examined by
      immunohistochemistry and found to be expressed in seven cases of nodal lymphomas
      and three cases of extranodal lymphomas, and two of these nodal cases were EBER
      ISH positive. In EBV serology, only two cases of nodal and one case of extranodal
      EBER positive B-cell lymphomas revealed a reactivation pattern. In the PCR study
      using primers to detect the lymphocyte-determined membrane antigen (LYDMA), the
      same sized monoclonal bands were observed in case 36 in the PCR products from the
      nose and skin, suggesting the monoclonal proliferation of the tumor. These
      findings suggested a low incidence of EBV association with B-cell lymphomas
      unless patients were in an immunologically impaired condition such as post-organ
      transplantation or autoimmune diseases.

PMID- 9631584
TI  - Vibrio vulnificus septicemia in a patient with severe aplastic anemia.
AB  - A 53-year-old man with severe aplastic anemia developed sporadic Vibrio
      vulnificus septicemia 1 day after eating raw fish and shellfish. Although V.
      vulnificus infection is potentially fatal, he was saved by immediate and
      sensitive antibiotic administration. Patients with chronic hematologic disease
      are susceptible to infection by this organism and are prone to developing
      septicemia when they eat raw seafood. It is necessary for a patient with this
      infection to be given effective antibiotics as quickly as possible.

PMID- 9631585
TI  - A case of therapy-related acute myeloblastic leukemia with t(16;21)(q24;q22)
      after chemotherapy with DNA-topoisomerase II inhibitors, etoposide and
      mitoxantrone, and the alkylating agent, cyclophosphamide.
AB  - A 59-year-old female suffering from malignant lymphoma developed therapy-related
      acute myeloblastic leukemia (t-AML) after chemotherapy consisting of treatment
      with DNA-topoisomerase II inhibitors, etoposide and mitoxantrone, and an
      alkylating agent, cyclophosphamide. The cumulative dose of etoposide
      administration was 5500 mg; 1500 mg given intravenously and 4000 mg orally. One
      year later, she suddenly developed AML of FAB M2. Cytogenetic analysis of bone
      marrow cells revealed deletion of 7q and a rare translocation, t(16;21)(q24;q22).
      Southern blot analysis of bone marrow cells did not detect rearrangement of the
      AML1 gene, however, fluorescence in situ hybridization (FISH) analysis of bone
      marrow cells at interphase and metaphase revealed a translocational splitting
      between chromosome 21 involving AML1 gene and chromosome 16. These results
      suggest that the breakpoint is not located in the breakpoint cluster region for
      t(8;21). The patient was treated with chemotherapy and entered complete
      remission.

PMID- 9631586
TI  - A high dose chemoradiotherapy and peripheral blood stem cell support combined
      with the CD34(+)-selection method in cyclin D1(+)-mantle cell lymphoma.
AB  - Mantle cell lymphoma (MCL) is currently regarded as one of the most incurable
      lymphomas, although reliable prognostic indicators are not yet to be defined. In
      a previous report, it was indicated that most of the patients with
      immunohistochemically cyclin D1(+)-MCL pursued the lethal clinical course within
      7 years, not having achieved complete remission (CR). Recently, a high dose
      chemoradiotherapy was carried out, this was supported by peripheral blood stem
      cell transplantation (PBSCT) using the CD34(+)-selection method in a 48-year-old
      female patient with cyclin D1(+)-MCL. The tumor cells were detected in her
      peripheral blood despite four courses of combination chemotherapy using CHOP
      regimen. Soon after the pre-conditioning of total body irradiation (TBI) and high
      dose melphalan, she received the PBSCT of 1.8 x 10(6)/kg CD34+ cells and showed
      rapid hematological recovery without life-threatening complications. The patient
      achieved CR and was alive, without disease, 730 days after PBSCT. Thus, CD34+
      selected PBSCT appears to provide further insight into the effective treatment
      and possible cure of this aggressive disease, i.e. cyclin D1(+)-MCL.

PMID- 9631587
TI  - A case of primary splenic large cell lymphoma with a t(9;14)(p13;q32).
AB  - t(9;14)(p13;q32), a subtype of 14q32 translocation, plays an essential role in
      the development of lymphoplasmacytoid lymphoma. t(9;14)(p13;q32) Causes
      juxtaposition of the PAX-5 gene on 9p13 and the IgH gene on 14q32, leading to the
      deregulation of the PAX-5 gene. We report a case of primary splenic lymphoma with
      a t(9;14). The histological diagnosis was diffuse large B-cell lymphoma without
      plasmacytoid differentiation. The lymphoma cells showed a complex karyotype
      including a t(9;14). Southern blot analysis localized the breakpoint of the PAX-5
      gene within a couple of kb regions upstream of the exon 1A, although the
      involvement of the PAX-5 gene with the immunoglobulin heavy chain gene could not
      be confirmed.

PMID- 9631588
TI  - Trisomy 12 and t(14;18) in B-cell chronic lymphocytic leukemia.
AB  - We report a case of B-cell chronic lymphocytic leukemia (B-CLL) in which trisomy
      12 and t(14;18)(q32;q21) were simultaneously detected in the same leukemic clone.
      Southern blot analysis showed that the BCL2/IgJH rearrangement occurred at the
      major breakpoint region in the hot spot of the BCL2 gene. Double color
      fluorescence in situ hybridization analysis using multiple probes indicated that
      clonal B-cell with t(14;18) represented a subpopulation of the total leukemic
      cells and that trisomy 12 followed t(14;18) as the cytogenetic aberration in the
      development of B-CLL. Our findings suggests that both the t(14;18) and the
      trisomy are secondary chromosomal changes in the leukemogenesis of B-CLL.

PMID- 9631589
TI  - Increase of platelet-associated IgG (PA-IgG) and hemophagocytosis of neutrophils
      and platelets in parvovirus B19 infection.

PMID- 9631590
TI  - Identifying health status and health risks of older rural residents.
AB  - Older rural residents are vulnerable in both health status and access to health
      services. This descriptive study was designed to assess the general health status
      and risk factors of older rural residents age 65 and over. Cluster analysis
      methods were used to group older adults into unique clusters of individuals with
      similar health risks. Although strategies are generally targeted at those with
      limitations in two or more activities of daily living, community health nurses
      might need to initiate interventions much earlier. Findings of this study can
      help community health providers, policymakers, and administrators strategically
      plan to meet the health care needs of various groups of at-risk older rural
      populations.

PMID- 9631591
TI  - Long-term care for elderly individuals and methods of financing.
AB  - As people age, there is an increase in chronic illness and disability and thus a
      growing need for long-term care. Unfortunately, the concept of long-term care can
      be very complex and confusing. Elderly individuals and their family members
      frequently have many questions, such as the following: What is long-term care,
      and who needs it? What long-term care services are available? Who will provide
      the services? Where will the services be provided? How much will the services
      cost, and who will pay for the expenses? Indeed, the cost of providing long-term
      care, whether in an institution or in one's own home, may represent an enormous
      burden for individuals and their families. Nurses, especially community health
      nurses, are in a prime position to address these questions and concerns to ensure
      appropriate care and services for their clients. This article addresses the
      questions clients frequently ask by defining long-term care and discussing long
      term care services, settings, and providers. In addition, 4 methods of financing
      long-term care will be presented.

PMID- 9631592
TI  - Health promotion lifestyles of women experiencing crises.
AB  - Women who are experiencing crisis situations, including homelessness, are often
      perceived as passive victims of their social, economic, and personal
      circumstances. A few studies have challenged the stereotype of homeless women as
      passive victims and demonstrated that they are active in seeking solutions to
      their problems (Hodnicki, Horner, & Boyle, 1992; Montgomery, 1994; Thrasher &
      Mowbray, 1995). This study surveyed women receiving assistance at a nurse-managed
      clinic that serves a homeless population to determine their health promotion
      strategies. On the basis of this study's findings, health care providers are
      encouraged to recognize and build on the strengths of women in crises at both the
      individual and community levels of care.

PMID- 9631593
TI  - Registered nurses' breast self-examination practice and teaching to female
      clients.
AB  - Many registered nurses (RNs) do not regularly perform breast self-examination
      (BSE), and even fewer routinely teach the procedure. The aim of this descriptive
      survey was to investigate registered nurses' BSE practice and teaching to female
      clients. A systematic random sample of 171 female Australian RNs aged 20 to 65
      who worked in acute or long-term care areas was surveyed. A questionnaire I
      developed and mailed to participants was used to collect the data, and
      descriptive statistics were used in data analysis. Ninety-three percent of
      participants reported performing BSE in the preceding 12 months. However, less
      than half (46%) had performed BSE monthly, and the major reason cited for not
      performing monthly BSE was "forgetting" (57%). Most participants (81%) stated
      they did not include the teaching of BSE in their nursing care; the major reason
      identified was "it was not relevant to their work context" (86%). However, 77%
      indicated feeling confident in teaching BSE, and most (94%) would teach BSE if
      they had the opportunity. Furthermore, participants were found to be more likely
      to teach BSE if they performed monthly BSE, felt confident with their BSE
      teaching skills, and had completed other nursing courses. The implications of
      this study are that nurses' teaching to clients may be increased if more emphasis
      on BSE occurs in the workplace and in undergraduate and postgraduate courses.
      Also, the provision of BSE educational programs is necessary to increase nurses'
      knowledge, confidence, performance, and teaching of BSE.

PMID- 9631594
TI  - Predictors of participation in prostate cancer screening at worksites.
AB  - Unfortunately, African American men have a higher incidence of and a higher
      mortality rate for prostate cancer than White men but are less likely to
      participate in prostate cancer screening. This correlational survey research
      identifies predictors for participation in a free prostate cancer screening in
      179 men, 64% of whom are African American. Each man was invited to see his
      personal physician for a free prostate cancer screening following a prostate
      cancer educational program given at his worksite. Forty-seven percent of the
      African American men went to their personal physician following the educational
      program and received a digital rectal examination (DRE) and a prostate specific
      antigen (PSA) screening. In the original cohort of educational program attendees,
      only 16% of the African Americans had obtained a DRE in the previous 12 months.
      However, 44% subsequently did participate in free DRE screening. Similarly, only
      6% of the African American men had received a PSA screening in the previous 12
      months, yet 42% obtained a PSA screening after the educational program, a
      sevenfold increase. Implications for allocating limited resources for education
      and screening to the high-risk group of African American men are discussed. This
      study's model of a prostate cancer educational program at worksites followed by
      attendees visiting their personal physician for screening could be replicated
      throughout the United States to increase African American men's participation in
      prostate cancer screening.

PMID- 9631595
TI  - Immunohistochemical and molecular studies on malignant transformation in mature
      cystic teratoma of the ovary.
AB  - OBJECTIVES: To determine a useful tumor marker for detecting squamous cell
      carcinoma arising in a dermoid cyst, and to find the molecular pathogenesis of
      this condition. METHODS: In 4 cases of squamous cell carcinoma arising in a
      dermoid cyst and 22 cases of dermoid cyst, we studied tissue expressions and
      serum levels of squamous cell carcinoma antigen (SCC), CA 19-9 and CA 125, and
      the mutation of the p53 tumor suppressor gene. RESULTS: Three of 4 malignant
      cases had either positive SCC expressions or elevated serum SCC levels. The mean
      serum SCC level in benign cases was below the cut-off level. CA 19-9 and CA 125
      were not detected in squamous cell carcinoma. p53 overexpressions were observed
      in all malignancies. CONCLUSION: These results suggested that the serum SCC might
      be a useful marker for detecting squamous cell carcinoma arising in a dermoid
      cyst, and that the mutation of p53 might be one of the genetic events in the
      malignant transformation of a dermoid cyst.

PMID- 9631596
TI  - Immunohistochemical evidence of the mesothelial histogenesis of a uterine
      adenomatoid tumor.
AB  - We present rare case of a uterine adenomatoid tumor. In order to characterize the
      diversity of immunoreactive antigens associated with mesothelial differentiation,
      we immunohistochemically examined the tumor's epithelioid and myofibromatoid
      components, as well as the biphasic pattern of its adenomatoid changes.
      Immunostaining of tumor cells was positive for high- and low-molecular-weight
      cytokeratins and vimentin. Specific immunoreactions with antibodies against
      desmin, alpha-actin, and the S-100 protein also were observed. The present
      adenomatoid tumor can be explained in terms of various transformations and
      typical alterations in mesothelioma cells: (1) the mesothelial cells had
      differentiated to epithelial and stromal components, concomitant with the
      presence of predominant reactive foci; (2) intermediate cells expressed different
      types of cytoskeletal intermediate filament proteins (IMPs); and (3) the patterns
      of fibromatoid and leiomyoid differentiation resembled those of a benign
      mesothelioma of the ovarian or oviductal peritoneum. Our immunohistochemical
      investigations indicated that the present tumor exhibited the histogenesis of a
      true mesothelioma, an adenomatoid mesothelioma.

PMID- 9631597
TI  - Silent premature rupture of membranes, detected and monitored serially by an AFP
      kit.
AB  - A 24-year-old woman underwent conization and cervical cerclage during pregnancy.
      After she later complained of fluid leakage, a premature rupture of the membranes
      (PROM) was suspected, because of positive results on a test for nitrazine, the
      intra-amniotic dye injection method (PSP test), and an AFP-kit test at 22 weeks
      of gestation. The nitrazine and PSP tests later turned negative. However, during
      the period from the 22nd through 26th weeks of gestation, the results of AFP-kit
      tests fluctuated, with repeated positive indications for bacterial cultures and
      elevated granulocyte elastase activity in the cervical mucus. The pregnancy was
      well maintained with administration of antibiotics and ritodrine hydrochloride
      until 34 weeks of gestation. The presence of chorioamnionitis, local inflammation
      of the fetal membranes, was found by pathological examination after the delivery.
      We propose a new clinical entity--to be referred to as silent PROM--the premature
      chemical rupture of the membranes.

PMID- 9631598
TI  - Primary term ovarian pregnancy superimposed by intrauterine pregnancy: a case
      report.
AB  - A case of primary ovarian pregnancy proceeding upto term superimposed by another
      intrauterine pregnancy is presented. Compound extrauterine and intrauterine
      pregnancy is a rare obstetric phenomenon and still rarer is a primary ovarian
      pregnancy proceeding upto the term. The condition was diagnosed at laparotomy
      during the second trimester of current pregnancy. Diagnostic laparotomy was done
      because the ovarian pregnancy was mimicking an ovarian tumur. The ovarian
      pregnancy was successfully managed by surgery. Normal vaginal delivery of a term
      intrauterine pregnancy occurred in due time. The difficulty of diagnosing the
      heterotopic pregnancy is discussed and the clinico-pathological features of
      primary term ovarian pregnancy is emphasized, as it is a very rare condition.

PMID- 9631599
TI  - Seroprevalence of toxoplasma antibodies among the antenatal population in
      Bangladesh.
AB  - OBJECTIVE: To determine the seroprevalence of toxoplasma antibodies toxoplasma
      IgG and toxoplasma IgM) among an antenatal population in a hospital of
      Bangladesh. METHODS: Sera from 286 pregnant women were tested for toxoplasma IgG
      antibody by applying enzyme linked immunosorbent assay (ELISA) technique. Among
      the 286 sera, 88 sera were randomly selected and tested for toxoplasma IgM
      applying ELISA. RESULTS: Among 286 patients 110 (38.5%) were positive for
      toxoplasma IgG antibody and among 88 patients only one (1.1%) was positive for
      toxoplasma IgM. The seroprevalence gradually increased with age and parity. The
      seroprevalence of antibody was higher among the women in poor (53.0%) than the
      upper socio-economic class (22.0%) and among the women with jobs (55.0%) than the
      housewife group (35.0%). CONCLUSION: This study shows that toxoplasmosis is
      endemic in Bangladesh and also affecting pregnant women. There is need for
      further detailed studies on toxoplasmosis and its influence on perinatal
      morbidity and mortality.

PMID- 9631600
TI  - Eclampsia: is there a seasonal variation in incidence?
AB  - OBJECTIVE: To clarify whether seasonal variation of temperature and humidity has
      any effect on the incidence of eclampsia. Eclampsia is the second major cause of
      maternal mortality in Pakistan. METHODS: Data was collected monthwise for the
      year 1996 from 4 large Govt. teaching hospitals of 4 provincial metropolis of
      Pakistan. Each province has diverse climate with considerable variation of air
      temperature and humidity. RESULTS: There were 395 cases of eclampsia amongst
      18,483 deliveries in 1996, giving an incidence of 2.14%. In Karachi (Sindh
      Province) with mild hot and humid climate and mild winter months, there was
      increase in eclampsia cases from April-July and in September. Otherwise the
      incidence remained stable. In Rawalpindi (Punjab Province) with moderately hot
      summer and cold winter, it was highest in hot season from May to September but
      was stable in winter. In Peshawar (N.W.F.P) and Quetta (Baluchistan Province)
      with more severe cold and dry winter the incidence peaked in winter and summer
      months both. CONCLUSIONS: The pattern of eclampsia cases showed variations in
      extremes of temperature but it was stable in mild weather. However, the
      statistical analysis revealed non-significant relationship of incidence of
      eclampsia with temperature when analysed by linear regression analysis.

PMID- 9631601
TI  - Vaginal birth after cesarean delivery: results in 310 pregnancies.
AB  - OBJECTIVE: To assess and compare the risk associated with a trial of vaginal
      birth after cesarean section (VBAC) with the risk of an elective repeat cesarean
      section. METHODS: A retrospective review of the records of 310 consecutive women
      who, at the Jichi Medical School Hospital in the 6-year period of 1990 through
      1995, had previously undergone a primary cesarean section and gave birth to a
      singleton infant weighing > or = 2,000 g at > or = 36 weeks of gestation in a
      subsequent pregnancy. RESULTS: Elective cesarean sections were performed on 96
      (31%) of 310 women, and VBACs were attempted by 214 women (69%). Vaginal
      deliveries were successful in 132 (43%) of the 310 pregnancies. No maternal death
      or perinatal deaths occurred in either group. A uterine rupture occurred in 2
      (0.9%) of the 214 women who attempted a VBAC, and 5 women (2.3%) gave birth to
      neonates with a 1-minute Apgar score < or = 6. None of the 96 women who underwent
      an elective cesarean section had such complications, although the difference in
      these complication rates did not reach a significant level. CONCLUSIONS: A trial
      of a VBAC significantly reduced the rate of cesarean sections. Although the rates
      of uterine rupture and neonatal asphyxia were slightly higher in women who
      attempted a VBAC than in women who underwent an elective cesarean section,
      obstetricians should offer the option of a trial of labor, because more than one
      half of the women with a previous cesarean delivery might have successful vaginal
      deliveries, and the VBAC-related maternal mortality rate does not reportedly
      differ between women undergoing a trial of labor and women undergoing an elective
      repeat cesarean section.

PMID- 9631602
TI  - Intrauterine therapy of fetal atrial flutter.
AB  - An increased awareness of fetal arrhythmias by obstetricians has resulted in a
      growing number of diagnosed cases of fetal cardiac problems. A fetus with atrial
      flutter diagnosed at 31 weeks of gestation was successfully converted to normal
      sinus rhythm in utero by maternal administration with digitalis. The fetal heart
      rate stayed in a normal rhythm with a maintenance dose of 0.5 mg/day. The fetus
      was delivered spontaneously at term and the neonatal heart rate has been in
      normal rhythm without any medical treatment.

PMID- 9631603
TI  - Abruptio placentae: risk factors and perinatal outcome.
AB  - OBJECTIVE: It is a case control study, conducted in order to determine the risk
      factors, and to find out the perinatal outcome of abruptio placentae in women
      delivered at the Princess Badeea Teaching Hospital in North Jordan. METHODS: We
      reviewed all cases of placental abruption delivered between 15th April 1994 till
      26 November 1995 and to compare that with pregnancies and deliveries not
      complicated by abruptio placentae. RESULTS: During the study period there were
      108 cases of abruptio placentae and 108 cases of the control group. The total
      number of women delivered were 18,256, so the incidence of abruptio placentae was
      5.9 per 1000 births. When compared to the control group, abruptio placentae
      occurred more in parous women (para > or = 5) (p < 0.0005), more preterm
      deliveries (p < 0.0001) with more birth weight < 2,500 g (p < 0.0001).
      Preeclampsia and pregnancy induced hypertension, intrauterine growth retardation,
      caesarean delivery, and intrauterine fetal death occurred more in patients with
      abruptio placentae. CONCLUSION: High parity, preeclampsia and hypertension are
      significant etiological determinants of abruptio placentae.

PMID- 9631604
TI  - Two uterine arterial management methods in laparoscopic hysterectomy.
AB  - OBJECTIVE: The purpose of this study was to evaluate whether laparoscopic
      separation with coagulation of the uterine arteries and uterosacral ligaments can
      be used in an attempt to improve the operative procedure when hysterectomy is
      carried out by laparoscopic and vaginal method. METHOD: A prospective study was
      carried out in 70 women who underwent laparoscopic hysterectomy excluding total
      laparoscopic hysterectomy. Laparoscopic uterine arterial separation with
      coagulation (include laparoscopic reperitonization) was performed after
      laparoscopic detachment of the bladder and resection of the broad ligament (or
      adnexa) in 39 cases (Group 1). Uterine artery was coagulated by bipolar
      electrocoagulator and separated from the uterine side wall by scissors. Endoloop
      tie was applied to the arterial pedicle, if bleeding occurred. Uterine arterial
      management was performed through the vaginal route (include vaginal
      reperitonization) after laparoscopic procedure which was finished at the lower
      part of broad ligament with bladder detachment in 31 cases (Group 2). RESULTS:
      The average duration of operation was 84.0 min and 101.8 min in Groups 1 and 2,
      respectively (p < 0.05). The average amount of bleeding was 154.8 ml and 298.4 ml
      in Groups 1 and 2, respectively (p < 0.05). Hemoglobin decreased in average by
      0.9 g/100 ml and 1.6 g/100 ml in Groups 1 and 2, respectively (p < 0.05).
      CONCLUSION: These results demonstrate that laparoscopic management of uterine
      arterial pedicles after bladder detachment could reduce the duration of operation
      time and amount of bleeding in laparoscopic hysterectomy.

PMID- 9631605
TI  - A case of mid-trimester intrauterine fetal death with Cushing's syndrome.
AB  - A 34-year-old woman was diagnosed with Cushing's syndrome after her first
      pregnancy ended in intrauterine fetal death at 25 weeks' gestation. She
      subsequently had a successful pregnancy after treatment of her disease. Although
      patients with Cushing's syndrome rarely conceive, abortion, preterm labor, and
      intrauterine growth retardation are common when they do.

PMID- 9631606
TI  - A case of primary non-Hodgkin's lymphoma of the uterine cervix treated by
      combination chemotherapy (THP-COP).
AB  - We present a case of primary non-Hodgkin's lymphoma of the uterine cervix, Ann
      Arbor stage IE. This 64-year-old multiparous Japanese woman showed markedly
      elevated serum levels of lactate dehydrogenase (LDH) and of soluble interleukin-2
      receptor (sIL-2R) at the time of diagnosis. Combination chemotherapy was
      administered and consisted of pirarubicin, cyclophosphamide, vincristine sulfate,
      and prednisolone (THP-COP). After 3 courses of such therapy, the serum levels of
      LDH and of sIL-2R decreased within normal limits, and the patient achieved a
      complete remission.

PMID- 9631608
TI  - Beware of toys.

PMID- 9631607
TI  - Ovarian endometrioid adenocarcinoma coexistent with benign and borderline
      endometrioid adenofibroma: a case report.
AB  - A well-differentiated endometrioid adenocarcinoma coexistent with benign and
      borderline-malignant endometrioid adenofibroma was found in the ovary of a 64
      year-old woman. She had vaginal bleeding caused by simple hyperplasia of the
      endometrium due to high levels of sex steroid hormones. A FIGO stage Ia solid
      ovarian tumor was identified. It was composed of irregularly shaped endometriotic
      glands with benign and borderline malignant cytologic features embedded in
      abundant fibromatous stroma. Well-differentiated malignant epithelium was
      adjacent to these areas, but fibromatous stroma was not predominant. She was
      treated by surgery and three cycles of chemotherapy. This paper describes this
      unusual tumor and reviews the literature.

PMID- 9631609
TI  - Building sound and regular teeth. The National Institute of Dental Research
      celebrates its golden anniversary.

PMID- 9631610
TI  - Fifty years of dental, oral and craniofacial research. The National Institute of
      Dental Research's Division of Intramural Research.

PMID- 9631611
TI  - Scientific progress in understanding oral and pharyngeal cancers.
AB  - Oral and pharyngeal cancers result from a complex interaction between genetic
      susceptibility and behavioral factors. Improved understanding of the underlying
      genetic events has led to insights about how oral and pharyngeal cancers develop
      and suggests promising new treatments. Tobacco and alcohol consumption are
      associated with most oral and pharyngeal cancers. Dental professionals' efforts
      to modify their patients' tobacco and alcohol use and to detect oral lesions at
      an early stage, together with scientific advances, will help reduce the impact of
      these cancers.

PMID- 9631612
TI  - Sjogren's syndrome: a model for dental care in the 21st century.
AB  - The diagnosis and treatment of Sjogren's syndrome, which poses many severe
      complications, should be of critical interest to dentists, who are often the
      first practitioners to detect symptoms. Dentistry is an integral part of health
      care delivery for patients with this condition. Management of Sjogren's syndrome
      can be seen as a model for the expanded scope of dental care in the future.

PMID- 9631613
TI  - Intrabony neurilemmoma: diagnosis and management.
AB  - The authors present a case of a mandibular neurilemmoma discovered on routine
      radiographic examination of an asymptomatic young woman. The lesion was
      surgically removed and there was no radiographic evidence of recurrence. A review
      of the literature is presented and the differential diagnosis, prognosis and
      treatment of this benign neurogenic tumor are discussed.

PMID- 9631614
TI  - Investigation of xerostomia in patients with rheumatoid arthritis.
AB  - The authors investigated the prevalence of xerostomia in a group of 604 subjects
      participating in a rheumatoid arthritis, or RA, study to explore the relationship
      of reduced salivary flow symptoms and demographic, clinical and medical
      characteristics. Forty-three percent of these subjects exhibited one or more
      severe xerostomia symptoms. Separate analyses revealed that the subjects who had
      the most physical disease symptoms were at greater risk of having reduced
      salivary flow. The study's results suggest that patients with RA should be
      screened for xerostomia symptoms so appropriate clinical interventions can be
      initiated.

PMID- 9631615
TI  - Dental cutting: the historical development of diamond burs.
AB  - This brief history of the dental diamond bur is intended to provide both a
      historical perspective and an evaluation of the current state of bur technology.
      An understanding of the origins of dental diamonds and the issues facing
      manufacturers transforms the dentist from a simple user into an informed
      consumer. The author contends that this can improve dental care and enable the
      dentist to collaborate with manufacturers in developing improved dental burs.

PMID- 9631616
TI  - The clinical longevity of porcelain veneers: a 48-month clinical evaluation.
AB  - The authors evaluated the clinical longevity of a brand of porcelain veneers and
      the accompanying cementation system. Fifty-nine porcelain veneers were prepared
      and placed in 12 patients by one practitioner and evaluated by two evaluators
      using modified Ryge criteria at baseline and 12 months. Fifty-three veneers were
      evaluated similarly at 48 months. Plaque index and gingival index scores were
      recorded as well. At 48 months, the veneers had stable color, all margins were
      clinically acceptable, there was no secondary caries and the patients reported no
      sensitivity.

PMID- 9631617
TI  - Survey of Medicaid child dental services in Washington state: preparation for a
      marketing program.
AB  - The authors surveyed Washington state dentists to gain an understanding of their
      participation in the Medicaid dental program, their willingness to learn more
      about the program and the degree of importance they attached to preventive care
      for preschool-aged children. They found that concerns about fees and
      administrative aspects predominated and concerns about client behaviors were
      expressed less often. Many dentists indicated a willingness to learn more about
      the program. These findings will be used to develop a plan to market the Medicaid
      program to Washington state dentists.

PMID- 9631618
TI  - Desensitization of cervical tooth structure.

PMID- 9631619
TI  - A technique for stabilizing gutta-percha carriers.

PMID- 9631620
TI  - Finding answers, finding other problem solvers.

PMID- 9631621
TI  - Advanced practice nursing: new opportunities for blended roles.

PMID- 9631622
TI  - Improving visual estimation of blood volume on peripads.

PMID- 9631623
TI  - Child and parent emotional responses during hospitalization for orthopaedic
      surgery.

PMID- 9631624
TI  - Child safety seat use in a midwestern Hmong community.

PMID- 9631625
TI  - The downward spiral of postpartum depression.

PMID- 9631626
TI  - Fetal alcohol syndrome--recognition and intervention.

PMID- 9631627
TI  - Research funding sources.

PMID- 9631628
TI  - Liability for unlicensed personnel, Part II.

PMID- 9631629
TI  - Don't give it away!

PMID- 9631630
TI  - Softly monitored.

PMID- 9631631
TI  - Advantages of the new progestins.

PMID- 9631632
TI  - Intra-arterial papaverine treatment for cerebral vasospasm: our experience and
      review of the literature.
AB  - We described the techniques and efficacy of intra-arterial papaverine
      hydrochloride infusion (IA-PAP) for symptomatic vasospasm due to aneurysmal
      subarachnoid hemorrhage based on our experience and review of the literature.
      Angiographic improvement occurred almost always, but only 50% of patients who
      presented with acute symptoms showed remarkable clinical improvement after the
      first, second, or third IA-PAP. Recurrent vasospasm after IA-PAP frequently
      occurred and this seems to be an apparent source of controversy regarding its
      efficacy. Review of the literature indicates that IA-PAP may be most effective in
      combination with percutaneous transluminal angioplasty. Further controlled
      studies should be conducted regarding papaverine's true efficacy including most
      effective papaverine concentration and rate of infusion, maximum total dose, site
      of infusion, timing of treatment, and selection of patients.

PMID- 9631633
TI  - Proliferative potential and apoptosis in rat glioma cell lines after
      hyperthermia.
AB  - The proliferative potential of cultured rat glioma cells (C6 and 9L) was
      evaluated after hyperthermia using immunohistochemical staining with
      bromodeoxyuridine (BrdU) and Ki-67 monoclonal antibodies. Apoptosis was assessed
      by in situ end-labeling of deoxyribonucleic acid breaks. Both BrdU and Ki-67
      labeling indexes decreased with increasing hyperthermia time. The decrease of the
      Ki-67 labeling index was not as great as that of the BrdU labeling index. The
      number of apoptotic cells increased with time after hyperthermia. These results
      indicate that the antitumor effect of hyperthermia may reflect the induction of
      apoptosis in the cells within the cell cycle, and the resultant reduction of the
      proliferative potential of surviving cells, especially in the S phase.

PMID- 9631634
TI  - Combined brachytherapy and external beam radiotherapy in normal monkey brains-
      experimental radiation necrosis evaluated by sequential magnetic resonance
      imaging.
AB  - Radiation-induced brain damage was evaluated using sequential magnetic resonance
      (MR) imaging in monkeys more than 1 year after either brachytherapy or combined
      brachytherapy and external beam radiotherapy (EBRT). MR images were obtained 1
      week, 1 month, 3 months, and subsequently every 3 months after brachytherapy, and
      the volume of the lesions was measured. In all four monkeys receiving only
      brachytherapy and three of the four animals receiving combined brachytherapy and
      EBRT, MR imaging revealed only transient extensive edema 1 week after treatment
      and ring enhancement, which was maximal 3 months after treatment, surrounding the
      implantation site. In one of the four animals undergoing combined brachytherapy
      and EBRT, MR images obtained 9 months after treatment showed an irregularly
      extending enhanced lesion with edema. MR images obtained 15 months after
      brachytherapy in this monkey showed the lesion extended into the contralateral
      hemisphere through the corpus callosum. Necropsy revealed severe radiation
      necrosis. This animal developed a very similar MR imaging presentation to that
      often encountered in human brains after combined brachytherapy and EBRT.

PMID- 9631635
TI  - Surgical indications for and limitations of staged transsphenoidal surgery for
      large pituitary tumors.
AB  - Surgical indications and limitations of transsphenoidal surgery and intentionally
      staged transsphenoidal surgery for large pituitary tumors were investigated by
      retrospective analysis of the surgical and neuroradiological findings of 22
      patients with large tumor and suprasellar extension. Twelve patients underwent
      intentionally staged transsphenoidal surgery, and 10 underwent combined
      transsphenoidal and transcranial surgeries. Successful removal by intentionally
      staged surgery required descent of the suprasellar part following the first
      transsphenoidal surgery. Analysis showed that a smooth suprasellar extension
      and/or soft tumor are indications for intentionally staged transsphenoidal
      surgery even in patients with small sella. However, lobulated suprasellar
      extension, fibrous and firm tumor without descent, and small sella with normal
      pituitary gland located at the bottom of the sella are contraindications for
      staged transsphenoidal surgery. The first transsphenoidal surgery is always
      indicated to achieve histological confirmation and decompression of optic nerves.
      Transcranial surgery should be attempted instead of repeated transsphenoidal
      surgeries when the residual tumor does not descend following the first
      transsphenoidal surgery.

PMID- 9631636
TI  - Visual recovery following immediate decompression of traumatic retrobulbar
      hemorrhage via transcranial approach.
AB  - A 17-year-old boy presented with retrobulbar hemorrhage manifesting as right
      proptosis, periorbital swelling, and blindness after suffering a midfacial
      trauma. Immediate decompression by removal of the retrobulbar hemorrhage via the
      transcranial approach was performed. The proptosis was resolved and visual acuity
      and eye movement were restored. Retrobulbar hemorrhage is a serious injury which
      may lead to blindness. However, recovery from blindness can be achieved with
      adequate management including neurosurgical decompression in the early stage.

PMID- 9631637
TI  - Cerebellar hemorrhage associated with moyamoya disease.
AB  - A 60-year-old female was admitted with complaints of severe headache, nausea, and
      vomiting. Computed tomography demonstrated a right cerebellar hematoma, which was
      surgically removed. Bilateral carotid angiography showed occlusions of the
      anterior and middle cerebral arteries, and abnormal vascular networks. Vertebral
      angiography showed a well developed posterior pericallosal artery. Left encephalo
      duro-arterio-synangiosis was performed. No cerebral vascular incident has been
      observed for 32 months.

PMID- 9631638
TI  - Intraosseous meningioma with a dural defect.
AB  - A 56-year-old female presented with a rare intraosseous meningioma associated
      with an unusual dural defect caused by invasion of the tumor. The underlying dura
      mater is normal or thickened in most cases of intraosseous meningiomas. Most
      intraosseous meningiomas are benign histologically, but they should be extirpated
      before invasion into the subdural space occurs.

PMID- 9631639
TI  - Primary malignant lymphoma of the brain in childhood.
AB  - A 5-year-old boy presented with a 1-year history of frontal headache and nausea.
      Neurological examination showed left abducens nerve palsy, left facial nerve
      palsy, Bruns' nystagmus, and wide-based gait. Neuroimaging demonstrated a lesion
      with moderate linear enhancement in the left cerebellar hemisphere. He underwent
      stereotactic needle biopsy. The histological diagnosis was well-differentiated
      small lymphocytic type of malignant lymphoma. Following the biopsy, the patient
      underwent radiotherapy (whole brain 30 Gy, local 20 Gy). He has been in good
      condition for more than 5 years. The long-term survival is attributable to the
      absence of aggressiveness and the good response to radiation of this subtype of
      malignant lymphoma.

PMID- 9631640
TI  - Intracranial pressure monitoring using a newly developed transducer-tipped
      ventricular drainage catheter.
AB  - A transducer-tipped ventricular drainage catheter (TVDC) was developed to allow
      continuous measurement of intracranial pressure (i.c.p.) without interrupting
      cerebrospinal fluid (CSF) drainage. The 8.5 Fr catheter with a double lumen has
      16 side holes for CSF drainage and a small silicone strain-gauge transducer on
      the side of the catheter tip to measure the ICP directly. The transducer is
      composed of a 2 x 1 mm2 silicone plate. Calibration must be performed before
      insertion. The calibrated catheter is inserted into the ventricles, usually via
      the anterior horn of the lateral ventricles to the foramen of Monro.
      Recalibration is not necessary even if the patient's head is tilted. The TVDC was
      applied to patients in whom ICP was suspected to be high and in whom the
      ventricles were large enough for tapping. The ICP wave form and values measured
      by the TVDC and the manometer method were equivalent. The drift phenomenon did
      not occur throughout the entire measurement period. The TVDC is very useful for
      both controlling and monitoring ICP.

PMID- 9631641
TI  - [XII Annual meeting of Applied Research in Chagas Disease. Uberaba, 25-27 October
      1996. Abstracts].

PMID- 9631642
TI  - [XIX Portuguese Congress of Cardiology. Vilamoura, 15-18 March 1998. Abstracts].

PMID- 9631643
TI  - Ambulatory health care visits by children: principal diagnosis and place of
      visit.
AB  - OBJECTIVES: This report presents national estimates of ambulatory health care use
      by children under 15 years of age according to principal diagnosis, place of
      visit (physician office, hospital outpatient department, and hospital emergency
      department), and patient characteristics (age, sex, and race). METHODS: Data were
      from the National Ambulatory Medical Care Survey and the National Hospital
      Ambulatory Medical Care Survey. Data were from 1993-95. RESULTS: In 1993-95
      children under 15 years of age made 165.3 million visits per year (289 visits per
      100 children). Visit rates were highest among infants and varied inversely with
      age. Visit rates were 43 percent higher among white children than black children.
      Three-quarters of ambulatory visits occurred in physician offices, 8 percent in
      hospital outpatient departments, and 14 percent in hospital emergency
      departments. Visits by white children were more likely to occur in physician
      offices than visits by black children (81 percent and 54 percent). Conversely,
      visits by black children were more likely to occur in hospital outpatient
      departments (19 percent and 7 percent) and hospital emergency departments (28
      percent and 12 percent) than visits by white children. The following principal
      diagnoses accounted for almost 40 percent of visits: well-child visit, 15
      percent; middle ear infection, 12 percent; and injury, 10 percent. Rates for well
      child visits were almost 80 percent higher among white infants than black
      infants. Continued monitoring of these differences in use of ambulatory care
      among children are needed, particularly in view of the possible impact of changes
      in the health care system on these differences.

PMID- 9631644
TI  - Trends in leprosy detection.

PMID- 9631645
TI  - Localized activation of RTK/MAPK pathways during Drosophila development.
AB  - Receptor tyrosine kinase (RTK) signaling is mediated by a signaling cascade
      culminating in activation of mitogen-activated protein kinase (MAPK) by double
      phosphorylation on threonine and tyrosine residues. The pattern of MAPK
      activation can now be directly visualized in situ during embryonic and adult
      development using an antiserum is specific for the double phosphorylated form of
      MAPK (db-P MAPK). The pattern of MAPK activation detected by this antiserum in
      developing embryos and larval imaginal discs conforms remarkably well to the
      inferred pattern of known RTK function. In addition, db-P MAPK staining directly
      reveals features of signaling such as the range of signal spreading and the
      kinetics of RTK activation, which would be difficult to measure by other methods.
      The ability to visualize the output of RTK signaling also permits detailed
      establishment of epistatic relationships between signaling components of RTK
      cascades.

PMID- 9631646
TI  - PCNA binding through a conserved motif.
AB  - Proliferating cell nuclear antigen (PCNA) has recently been identified as a
      target for the binding of several proteins. The cell cycle regulatory protein,
      p21, and the replication endonuclease, Fen1, have already been described as
      competing for PCNA binding. Two recent reports have identified DNA (cytosine
      5)methyltransferase (MCMT) and the DNA repair endonuclease XPG as binding to
      PCNA. The remarkable thing about these interactions is that they all seem to
      occur through a conserved motif that is likely to contact the same site on PCNA.
      This has fascinating implications for a regulatory network linking these diverse
      protein functions.

PMID- 9631647
TI  - Conditional genome alteration in mice.
AB  - The recent ability to inactivate specific genes in mice has significantly
      accelerated our understanding of molecular, cellular, and even behavioral aspects
      of normal and disease processes. However, this ability has also demonstrated the
      extreme complexity of genetic determination in mammals, in particular, that genes
      in the same family or pathway can be functionally redundant and that a given gene
      often has multiple roles. Thus, inactivation of a gene often does not indicate
      its complete spectrum of functions. To circumvent this problem, many new tools
      and novel applications of classic techniques have been developed to place spatial
      and temporal restrictions on the genomic alterations. These approaches include
      chimera and mosaic studies, organ transplantation, complementation assays,
      dominant negative mutants, conditional gene knockouts, and lineage-specific gene
      rescue. Not only has this opened up more sophisticated ways to make genomic
      alterations, but it has provided the opportunity to create animal models for
      sporadic human genetic diseases.

PMID- 9631648
TI  - Positive and negative signals between interacting cells for establishing neural
      fate.
AB  - Specifying multiple cell types from a population of initially equivalent cells is
      a fundamental process in the development of all multicellular organisms. Neural
      development in the fruit fly Drosophila melanogaster provides an excellent venue
      in which to examine mechanisms of cell fate specification. Inhibitory cell-cell
      interactions mediated by genes of the Notch-Delta signaling pathway govern the
      selection of neural and epidermal fates among cells with equivalent developmental
      potential in a process termed lateral inhibition. Recent data on the roles of
      genes such as Notch, Delta, and kuzbanian warrant a rethinking of the lateral
      inhibition model. Furthermore, evidence for a positive signaling pathway
      promoting the neural fate among equivalent cells suggests that this mechanism
      acts in addition to lateral inhibition to specify cell fate. A balance of
      opposing signals may be necessary to correctly partition cells of different types
      from an initially homogeneous population of cells.

PMID- 9631649
TI  - Eukaryotic DNA topoisomerase II beta.
AB  - Type II DNA topoisomerase activity is required to change DNA topology. It is
      important in the relaxation of DNA supercoils generated by cellular processes,
      such as transcription and replication, and it is essential for the condensation
      of chromosomes and their segregation during mitosis. In mammals this activity is
      derived from at least two isoforms, termed DNA topoisomerase II alpha and beta.
      The alpha isoform is involved in chromosome condensation and segregation, whereas
      the role of the beta isoform is not yet clear. DNA topoisomerase II beta was
      first reported in 1987. Here we review the research on DNA topoisomerase II beta
      over the last 10 years.

PMID- 9631650
TI  - Somatic hypermutation of antibody genes: a hot spot warms up.
AB  - In the course of an immune response, antibodies undergo affinity maturation in
      order to increase their efficiency in neutralizing foreign invaders. Affinity
      maturation occurs by the introduction of multiple point mutations in the variable
      region gene that encodes the antigen binding site. This somatic hypermutation is
      restricted to immunoglobulin genes and occurs at very high rates. The precise
      molecular basis of this process remains obscure. However, recent studies using a
      variety of in vivo and in vitro systems have revealed important regulatory
      regions, base motifs that are preferred targets of mutation and evidence that
      transcription may play an active role in hypermutation.

PMID- 9631651
TI  - Reeler: new tales on an old mutant mouse.
AB  - Neurological mouse mutants provide an opportunity to dissect the complex
      mechanisms that underlie vertebrate brain development. Advances in genetic
      technologies have permitted the identification of genes disrupted in many
      mutants, allowing a molecular interpretation of the phenotypes. For several
      decades, the spontaneous mutant mouse reeler has been used as a model for the
      analysis of the development of laminated brain structures. In this ataxic mutant,
      the migration of many neurons is aberrant, resulting in disrupted cellular
      organization. Recently, reelin, the gene disrupted in the reeler mouse, has been
      identified, reelin encodes a novel extracellular molecule that controls neural
      cell positioning through mechanisms that are not yet completely understood.
      Analysis of the expression pattern and the properties of the reelin gene product
      (Reelin) suggests models for its function during brain development. Furthermore,
      the recent identification of genes that may function in the Reelin signaling
      pathway advances our knowledge of the molecular basis of neuronal migration.

PMID- 9631652
TI  - Have gene knockouts caused evolutionary reversals in the mammalian first arch?
AB  - Many recent gene knockout experiments cause anatomical changes to the jaw region
      of mice that several investigators claim are evolutionary reversals. Here we
      evaluate these mutant phenotypes and the assertions of atavism. We argue that
      following the knockout of Hoxa-2, Dlx-2, MHox, Otx2, and RAR genes, ectopic
      cartilages arise as secondary consequences of disruptions in normal processes of
      cell specification, migration, or differentiation. These disruptions cause an
      excess of mesenchyme to accumulate in a region through which skeletal progenitor
      cells usually migrate, and at a site of condensation that is normally present in
      mammals but that is too small to chondrify. We find little evidence that these
      genes, when disrupted, cause a reversion to any primitive condition and although
      changes in their expression may have played a role in the evolution of the
      mammalian jaw, their function during morphogenesis is not sufficiently understood
      to confirm such hypotheses.

PMID- 9631653
TI  - My favorite cell: Giardia.
AB  - The gut protozoan parasite, Giardia duodenalis, is the best characterized example
      of the most ancient eukaryotes, which are anaerobic and appear to be primitively
      amitochondrial. Apart from its obvious medical importance, Giardia is fascinating
      in its own right. Its prokaryotic-like anaerobic metabolism renders it
      selectively sensitive to some bacterial drugs, especially the nitroimidazoles,
      which are activated to form toxic radicals. Other features, including an enzyme
      that reduces oxygen directly to water, cysteine as the keeper of redox balance, a
      plasmid, and toxin-like genes are also distinctly prokaryotic-like. But, unlike
      prokaryotes, Giardia has a sophisticated, highly developed cytoskeleton, bounded
      nuclei, linear chromosomes capped with telomeric repeats, and telomere positional
      regulation of gene expression.

PMID- 9631654
TI  - Interactions between SRY and SOX genes in mammalian sex determination.
AB  - The SRY gene on the mammalian Y chromosome undoubtedly acts to determine testis,
      but it is still quite unclear how. It was originally supposed that SRY acts
      directly to activate other genes in the testis-determining pathway. This paper
      presents an alternative hypothesis that SRY functions indirectly, by interacting
      with related genes SOX3 (from which SRY evolved) and SOX9 (which appears to be
      intimately involved in vertebrate gonad differentiation). Specifically, I propose
      that in females SOX3 inhibits SOX9 function, but in males, SRY inhibits SOX3 and
      permits SOX9 to enact its testis-determining role. This hypothesis makes testable
      predictions of the phenotypes of XX and XY individuals with deficiencies or
      overproduction of any of the three genes, and is able to account for the
      difficult cases of XX(SRY-) males and transdifferentiation in the absence of SRY.
      The hypothesis also suggests a way that the dominant SRY sex-determining system
      of present-day mammals may have evolved from an ancient system relying on SOX3
      dosage.

PMID- 9631655
TI  - A growing family of Notch ligands.
AB  - Signaling through Notch-like receptors is an evolutionarily well-conserved
      mechanism for cell-cell communication. Transmembrane ligands of the DSL (Delta,
      Serrate, LAG-2) family signal to Notch receptors on a neighboring cell, which
      results in an intracellular signaling cascade, influencing cellular
      differentiation. Recently published data shed new light on the repertoire of
      ligands and on processing of Notch receptors. One report provides evidence for a
      novel, more distantly related ligand of the Delta-type in mouse, DII3 (Delta-like
      3). Ectopic expression of DII3 perturbs primary neurogenesis in frog embryos in a
      manner expected for a bona fide Notch ligand. Two reports provide new information
      about processing of Notch receptors. A novel protease, Kuzbanian, is identified,
      which cleaves the Notch receptor at the extracellular side. Biochemical
      experiments show that the cleavage probably occurs during intracellular
      trafficking, and that only processed Notch receptors appear at the cell surface.
      Taken together, these reports extend our knowledge about an important event in
      cell-cell communication--how Notch ligands and receptors meet and interact.

PMID- 9631656
TI  - Methuselah meets diabetes.
AB  - Mutations in the daf-2 and age-1 genes cause constitutive dauer larva formation
      and double adult life span in C. elegans. Their effect on life span has excited
      considerable interest and their effect on dauer formation has facilitated rapid
      progress in their genetic and molecular analysis. Two recent papers report that
      daf-2 encodes a member of the insulin-receptor family and that age-1 encodes a
      PI3 kinase subunit, a second-messenger producing enzyme known to act downstream
      of the mammalian insulin receptor. These findings provide the first mechanistic
      insight into the well-established link between metabolism and aging.

PMID- 9631657
TI  - Shaping animal body plans in development and evolution by modulation of Hox
      expression patterns.
AB  - Most animals exhibit distinctive and diverse morphological features on their
      anterior-posterior body axis. However, underneath the variation in design and
      developmental strategies lies a shared ancient structural blueprint that is based
      on the expression patterns of Hox genes. Both the establishment and maintenance
      of the spatial and temporal distribution of Hox transcripts play an important
      role in determining axial pattern. The study of many animal systems, both
      vertebrate and invertebrate, suggests that the mechanisms used to establish Hox
      transcription are nearly as diverse as the body plans they specify. The
      strategies for maintenance of Hox expression pattern seem more conserved among
      different phyla, and rely on the action of Pc and trx group genes as well as auto
      and cross-regulation among Hox genes. In mice, the sharing of regulatory
      elements coupled with auto- and cross-regulation could explain the conservation
      of the clustered arrangement of Hox genes. In contrast, fly Hox genes seem to
      have evolved insulators or boundary elements to avoid sharing regulatory regions.
      Differences in Hox transcription patterns can be correlated with morphological
      modifications in different species, and it seems likely that evolutionary
      variation of Hox cis-regulatory elements has played a major role in the emergence
      of novel body plans in different taxa of the animal kingdom.

PMID- 9631658
TI  - Using mitochondrial and nuclear DNA markers to reconstruct human evolution.
AB  - Molecular genetic-data have greatly improved our ability to test hypotheses about
      human evolution. During the past decade, a large amount of nuclear and
      mitochondrial data have been collected from diverse human populations. Taken
      together, these data indicate that modern humans are a relatively young species.
      African populations show the largest amount of genetic diversity, and they are
      the most genetically divergent population. Modern human populations expanded in
      size first on the African continent. These findings support a recent African
      origin of modern humans, but this conclusion should be tempered by the possible
      effects of factors such as gene flow, population size differences, and natural
      selection.

PMID- 9631659
TI  - Nerve growth factor: two receptors, multiple functions.
AB  - Nerve growth factor (NGF) was characterized over 4 decades ago, and like the
      other neurotrophins subsequently discovered, it is best known for its trophic
      role, including the prevention of programmed cell death in specific populations
      of neurones in the peripheral nervous system. This property can be accounted for
      by the activation of a tyrosine kinase receptor. NGF also regulates neuronal
      function, as illustrated by its role in pain and inflammation, and in synaptic
      plasticity. Finally, NGF recently was shown to activate the neurotrophin receptor
      p75 (p75NTR), a receptor with no intrinsic catalytic activity and with
      similarities to members of the tumor necrosis factor receptor family. During
      normal development, the activation of p75NTR by NGF actually kills cells in the
      central nervous system. One remarkable property of NGF is then that it controls
      cell numbers in opposite ways in the developing nervous system, a result of its
      unique ability to activate two different receptor types.

PMID- 9631660
TI  - Dual functions of DNA repair genes: molecular, cellular, and clinical
      implications.
AB  - The complex series of DNA repair pathways that are used to repair damage to
      cellular DNA employ many different proteins. A substantial number of these have
      second functions. Defects in these multifunctional proteins in man can lead to
      widely differing clinical phenotypes depending on which of the functions is
      affected. This is illustrated most clearly in the transcription factor TFIIH,
      which is involved in both basal transcription and nucleotide excision repair.
      Different mutations in genes encoding TFIIH subunits can result in the highly
      cancer-prone repair disorder xeroderma pigmentosum, or the noncancer-prone
      multisystem disorder trichothiodystrophy, the features of which are probably a
      consequence of abnormalities in transcription. The involvement of repair proteins
      in other processes also poses interesting evolutionary questions.

PMID- 9631661
TI  - Glycosaminoglycan-protein interactions: definition of consensus sites in
      glycosaminoglycan binding proteins.
AB  - Although interactions of proteins with glycosaminoglycans (GAGs), such as heparin
      and heparan sulphate, are of great biological importance, structural requirements
      for protein-GAG binding have not been well-characterised. Ionic interactions are
      important in promoting protein-GAG binding. Polyelectrolyte theory suggests that
      much of the free energy of binding comes from entropically favourable release of
      cations from GAG chains. Despite their identical charges, arginine residues bind
      more tightly to GAGs than lysine residues. The spacing of these residues may
      determine protein-GAG affinity and specificity. Consensus sequences such as
      XBBBXXBX, XBBXBX and a critical 20 A spacing of basic residues are found in some
      protein sites that bind GAG. A new consensus sequence TXXBXXTBXXXTBB is
      described, where turns bring basic interacting amino acid residues into
      proximity. Clearly, protein-GAG interactions play a prominent role in cell-cell
      interaction and cell growth. Pathogens including virus particles might target GAG
      binding sites in envelope proteins leading to infection.

PMID- 9631663
TI  - Underground metabolism.
AB  - All enzymes are able to use alternative substrates. When these are naturally
      occurring metabolites, an 'underground reaction' takes place. Examples are
      presented in which underground metabolism of this sort produces an observable
      phenotype. Although biological processes can be remarkably accurate, evolution
      has selected error rates far from perfect. It is suggested here that a certain
      level of metabolic inaccuracy, in addition to saving energy, may also confer an
      evolutionary advantage, for example by providing metabolic plasticity. Since
      underground reactions are unpredictable from DNA sequence data, caution is in
      order when interpreting correlations between genetic disorders and pathological
      syndromes.

PMID- 9631662
TI  - Contributions of blastocyst micromanipulation to the study of mammalian
      development.
AB  - This is a personal account of why the author chose to focus on devising
      techniques for micromanipulating the blastocyst stage conceptus as a way of
      investigating early development in mammals. Its aim is to provide insight into
      what such technical innovations entailed and how they have contributed to present
      understanding of both embryology and the analysis of gene function in mammals.
      The ability to dissect and reconstitute mouse blastocysts, and to inject cells or
      tissue into them, enabled genes to be harnessed as markers for elucidating the
      lineage of cells and interactions between tissues from the stage when
      differentiation is first evident. Most importantly, it made it possible to apply
      clonal analysis to the study of cell fate in mammals. The scope of blastocyst
      micromanipulation was further enhanced when embryonal carcinoma (EC) cells and,
      particularly, embryonic stem (ES) cells were found to be able to participate in
      normal development and contribute to the germ line following injection into the
      blastocyst.

PMID- 9631664
TI  - Assessment of malingering with simulation designs: threats to external validity.
AB  - Comprehensive forensic evaluations are predicated on the accurate appraisal of
      response styles that may affect evaluatees' clinical presentation and experts'
      conclusions associated with psycholegal issues. In the assessment of malingering,
      forensic experts often rely heavily on standardized measures that have been
      validated exclusively via analogue research. While such research augments
      internal validity, the threats to external validity are readily apparent. As the
      first study of these threats, type of incentive (positive versus negative),
      context (a familiar versus unfamiliar scenario), and relevance to the
      participants was investigated systematically with a between-subjects factorial
      design. A sample of 231 undergraduates was asked to either (a) feign major
      depression and given an easily understood description of this disorder or (b)
      serve as controls responding honestly. They were administered a brief measure of
      psychopathology (Hopkins Symptom Checklist; Derogatis, Lipman, Rickels,
      Uhlenhuth, & Covi, 1974) and a recent screen for malingering (Screening Inventory
      of Malingered Symptoms or SIMS; Smith, 1992) in 1 of 18 experimental conditions.
      Results suggested that incentive had a main effect on the SIMS. More
      specifically, simulators under negative incentives appeared more focused in their
      feigning; they produced more bogus depressed symptoms, but fewer symptoms
      unrelated to depression. Interactions were also observed between context and
      incentive, and context and relevance. Implications of these results are explored
      for both analogue research on malingering and current forensic practice.

PMID- 9631665
TI  - Screening for malingering in a correctional setting.
AB  - This study outlines the development of the Screening SIRS, an abbreviated version
      of the Structured Interview of Reported Symptoms (SIRS), for use as a screening
      measure of malingering in a correctional setting. Seventy-five inmates
      complaining of psychological impairment were tested for malingering. A subset of
      the participants was given both the original SIRS and the Screening SIRS as a
      separate test with the test order counterbalanced; the remainder were given the
      original SIRS and a derived classification was determined by extracting the
      Screening SIRS scale scores. Using Receiver Operating Characteristic analyses,
      classification based on the Screening SIRS was significantly better than chance.
      With a sensitivity of 87% and specificity of 73%, the Screening SIRS was highly
      predictive of classifications based on the original SIRS. These findings have
      instrumental implications in correctional settings where identification of
      possible malingerers through a screening procedure may facilitate optimal
      allocation of resources.

PMID- 9631666
TI  - Age-related changes in the tiger salamander retina.
AB  - Tiger salamanders have been used in visual science because of the large size of
      their cells and the ease of preparation and maintenance of in vitro retinal
      preparations. We have found that salamanders over 27 cm in length show a variety
      of visual abnormalities. Compared to smaller animals (15-23 cm), large animals
      exhibited a decrease in visual responses determined by tests of the optomotor
      reflex. Small animals responded correctly an average of 84.5% of the time in
      visual testing at three light levels compared to an average of 68.4% for the
      large animals with the poorest visual performance at the lowest level of
      illumination. In addition, large animals contained (i) histological degeneration
      of the outer retina, in particular, loss and disruption of outer segments and
      abnormalities of the retinal pigmented epithelium, (ii) loss of cells, including
      photoreceptors, by apoptosis as evaluated with the TUNEL technique, and (iii) an
      increase in the number of macrophages and lymphocytes within the retina as
      determined by morphological examination. These histological changes were present
      in all large animals and all quadrants of their retinas. In contrast, small
      animals showed virtually no retinal degeneration, no TUNEL-positive cells, and
      few immune-like cells in the retina. Since large animals are also older animals.
      the visual changes are age-related. Loss of visual function and histological
      degeneration in the outer retina also typify aged human eyes. Thus, we propose
      that large salamanders serve as an animal model for age-related retinal
      degeneration. In addition to providing a source of aging retina that is readily
      accessible to experimental manipulation, the salamander provides a pigmented
      retina with a mixed (2:1, rod:cone) population of photoreceptors, similar to the
      degeneration-prone parafoveal region of the human eye.

PMID- 9631667
TI  - Rethinking contraindications to vaccination.

PMID- 9631668
TI  - Radical prostatectomy: what do the patients really think of surgery?

PMID- 9631669
TI  - Does Lyme disease exist in Australia?

PMID- 9631670
TI  - The MJA: what our readers say.

PMID- 9631671
TI  - Health-related quality of life in Australian men remaining disease-free after
      radical prostatectomy.
AB  - OBJECTIVE: To determine the health-related quality of life (HRQOL) of Australian
      men after radical prostatectomy. DESIGN: Cross-sectional study. SETTING: Private
      and public practices of three urologists in south-east Queensland, July 1989 to
      June 1995. PARTICIPANTS: 140 men with no evidence of disease recurrence 1 to 6
      years after radical prostatectomy. MAIN OUTCOME MEASURES: Voiding and erectile
      potency and HRQOL. Recall of preoperative status and status at survey were
      established by an independently administered multi-item questionnaire. RESULTS:
      112 men (80%) completed the study questionnaire. Difficulty with bladder control
      before the operation was reported by 25 (22%; 95% confidence interval [CI], 15%
      31.2%), and the incontinence rate after treatment was 22/112 (20%; 95% CI, 12.7%
      28.2%). Men with incontinence after operation were more likely to recall
      preoperative urinary symptoms. Eighty-four (75%) men were happy or coping with
      their sexual function after radical prostatectomy despite an erectile potency
      rate of only 12% (95% CI, 7%-20%). Twenty-eight (25%) had tried penile injections
      and three have had penile prostheses since their operation. Impotence was
      reported more frequently (40%) as the treatment-related problem most affecting
      life, followed by "concern about cancer" (12%) and incontinence (8%). Impotence
      was also the most common cause given for diminished HRQOL. CONCLUSIONS: Loss of
      sexual function after radical prostatectomy is more commonly perceived as a major
      problem and is more likely than urinary incontinence to adversely affect HRQOL.
      Loss of sexual function and its effect on HRQOL needs to be given greater
      emphasis in counselling before radical prostatectomy.

PMID- 9631672
TI  - Home vaccination for children behind in their immunisation schedule: a randomised
      controlled trial.
AB  - OBJECTIVE: To ascertain the effectiveness of a home vaccination service for
      children behind in their vaccination schedule. DESIGN: Randomised controlled
      trial of nurse-administered vaccination at home. Children were allocated at
      random to the intervention or the control group before any contact with the
      parents was made. SETTING: 10 council areas in north-west metropolitan Melbourne
      defined by 56 postcode zones. Six-week intervention period from November 1996.
      PARTICIPANTS: 405 children--all those in the study area (n = 2610) 90 days late
      (age 9 months) for their third diphtheria-tetanus
      pertussis/poliomyelitis/Haemophilus influenzae type B (DTP/OPV/Hib) vaccination,
      or 120 days late (age 16 months) for their measles-mumps-rubella (MMR)
      vaccination, according to the Australia Childhood Immunisation Register. MAIN
      OUTCOME MEASURES: Number of children completing DTP/OPV/Hib or MMR during the
      intervention period, and number up to date before intervention. RESULTS:
      Verification of vaccination status with the parents revealed that 123 (60%) of
      the children in the intervention group and 113 (56%) of those in the control
      group were up to date with their vaccinations, leaving a study population of 81
      (intervention group) and 88 (control group). Vaccination was achieved in 46 (57%)
      intervention children and 24 (27%) control children (risk ratio [RR], 2.08; 95%
      CI, 1.4-3.1; P < 0.001). For DTP/OPV/Hib, 18/32 (56%) intervention children and
      12/36 (33%) control children were vaccinated, (P = 0.06). For MMR, 28/49 (57%)
      and 12/52 (23%) children were vaccinated, respectively (P < 0.001). Home
      vaccinations were completed with 26 families (including five siblings). The
      average cost per child vaccinated as a result of the home program was $92.52.
      CONCLUSION: Home vaccination for children behind in their immunisation schedule
      is an effective, acceptable and relatively cheap method of completing recommended
      vaccinations. We recommend that a home vaccination program be widely implemented
      and made available, particularly for disadvantaged families.

PMID- 9631673
TI  - Vaccinating children with a history of serious reactions after vaccination or of
      egg allergy.
AB  - OBJECTIVE: To describe the results of vaccinating children with a history of
      serious adverse reactions after vaccination or of egg allergy at a special clinic
      established for that purpose. DESIGN: Retrospective case series. PATIENTS:
      Children who attended the clinic between 1 August 1994 and 31 July 1996 after
      being referred by vaccine providers. SETTING: A clinic conducted in the Emergency
      Department of The Canberra Hospital, Australian Capital Territory. MAIN OUTCOME
      MEASURES: Reasons for referral; vaccinations given; and subsequent adverse
      vaccination events. RESULTS: 91 children received 155 vaccinations at the clinic,
      and only one serious event--a hypotonic/hyporesponsive episode (HHE) after
      diphtheria-tetanus-whole-cell pertussis (DTPw), oral polio and Haemophilus
      influenzae type b vaccination--was subsequently reported; this child recovered
      spontaneously. Fifty-three children referred because of a previous serious
      adverse vaccination event were revaccinated at the clinic with whole-cell
      pertussis vaccine (47), combined diphtheria and tetanus vaccine (4), tetanus
      toxoid (1), and typhoid vaccine (1). Three children (referred because of previous
      meningitis, subdural haemorrhage or parental suspicion of allergy to DTPw)
      received their first dose of pertussis vaccine at the clinic. The remaining 35
      children had a history of egg allergy and were given measles-mumps-rubella
      vaccine. CONCLUSIONS: We successfully vaccinated children with histories of
      serious reactions to vaccination, including HHEs, convulsions, apnoea, high
      temperatures and persistent screaming, as well as those with egg allergy. We
      believe special clinics can improve vaccination coverage.

PMID- 9631674
TI  - Clozapine treatment in Australia: a review of haematological monitoring.
AB  - BACKGROUND: Clozapine is an atypical antipsychotic drug indicated for patients
      with schizophrenia in whom traditional antipsychotic drugs (such as haloperidol
      or the phenothiazines) are ineffective, or in those who experience intolerable
      adverse effects. Clozapine treatment may be complicated by the development of
      life-threatening agranulocytosis, so regular haematological monitoring is
      required. OBJECTIVES: To determine the incidence of clozapine-induced
      agranulocytosis in Australia and the importance of monitoring white blood cell
      counts in patients treated with clozapine. DESIGN: Review of haematological
      monitoring for the first three years (June 1993-July 1996) of operation of the
      Australian Clozaril (clozapine; Novartis Australia) Patient Monitoring System
      (CPMS) central database. RESULTS: In the 4061 patients prospectively monitored by
      the CPMS, the incidence of agranulocytosis, neutropenia and leukopenia combined
      was 2.6% (n = 104); the incidence of agranulocytosis was 0.9% (n = 37). So far
      there have been no deaths in Australia from the complications of clozapine
      induced agranulocytosis. CONCLUSION: The incidence of agranulocytosis and
      neutropenia associated with clozapine use in Australia is similar to that in the
      rest of the world. Monitoring the white blood cell counts of patients being
      treated with clozapine ensures minimal risk to patients who develop
      agranulocytosis.

PMID- 9631675
TI  - Culture-positive Lyme borreliosis.
AB  - We report a case of Lyme borreliosis. Culture of skin biopsy was positive for
      Borrelia garinii, despite repeated prior treatment with antibiotics. The patient
      had travelled in Europe 17 months before the onset of symptoms, but the clinical
      details indicate that the organism could have been acquired in Australia. The
      results of conventional serological and histopathological tests were negative,
      despite an illness duration of at least two years.

PMID- 9631676
TI  - Future of medical training in Australia.

PMID- 9631677
TI  - Functional (non-ulcer) dyspepsia: unexplained but not unmanageable.
AB  - Functional dyspepsia--defined as chronic or recurrent pain or discomfort centred
      in the upper abdomen, with no clinical or endoscopic evidence of known organic
      disease--is very common and causes considerable morbidity and loss of
      productivity. A first priority in management is reassuring patients that they do
      not have a serious disorder. Few drugs have established benefit and the choice
      depends on which symptoms predominate--prokinetic drugs may be most beneficial in
      those in whom discomfort (rather than pain), bloating or nausea is the most
      bothersome complaint and antisecretory drugs in those with predominant epigastric
      pain.

PMID- 9631678
TI  - Xenotransplantation: do the risks outweigh the benefits?

PMID- 9631679
TI  - Venlafaxine overdose.

PMID- 9631680
TI  - Serotonin syndrome in combined moclobemide and venlafaxine ingestion.

PMID- 9631681
TI  - The risk of venous thrombosis following gynaecological laparoscopic surgery.

PMID- 9631682
TI  - Intrauterine pregnancies following laparoscopic tubal reanastomosis.

PMID- 9631683
TI  - Intrauterine pregnancies following laparoscopic tubal reanastomosis.

PMID- 9631684
TI  - Local impact of the NHMRC early breast cancer guidelines.

PMID- 9631685
TI  - Trends in asthma mortality in Australia, 1960-1996.

PMID- 9631686
TI  - Public health and politics: the demise of the ACT heroin trial.

PMID- 9631687
TI  - Is health care card status related to consultation time?

PMID- 9631688
TI  - Should there be an accredited ethics committee system for centralised review of
      multicentre clinical research?

PMID- 9631689
TI  - [Apropos of sublingual specific immunotherapy].

PMID- 9631690
TI  - [Urticarial vasculitis].
AB  - Urticarial vasculitis is defined by association of an urticaria and/or angio
      oedema and a vasculitis of the small dermal vessels, leucocytoclastic or
      mononuclear. Sometimes it is an acute urticaria, of infectious or drug origin.
      Urticarian vasculitis may also be due to pressure or cold. But usually, it is a
      chronic urticaria that readily accompanies systemic signs and immunological
      anomalies, in particular hypocomplementemia. The clinical-biological picture
      becomes a true entity or is associated with another condition, most often a
      collagenosis.

PMID- 9631691
TI  - Kinetics of eosinophil cationic protein release in mite-allergic rhinitis after
      specific nasal provocation.
AB  - Nasal allergen challenges, despite not reproducing exactly natural allergen
      exposures, are a useful method to try to understand the complex mediator and
      cellular kinetics as well as the cellular interactions triggered by allergen
      exposure in allergic rhinitis. In this article we evaluated the kinetics of
      Eosinophil Cationic Protein (ECP) release into nasal lavage fluid after nasal
      allergen challenge. Our results have shown heterogeneity in ECP kinetics,
      probably due to heterogeneous activation of the eosinophils already present in
      the nasal mucosa of perennial allergic rhinitis patients. More studies in this
      field are needed to evaluate the effect of specific immunotherapy and/or
      prolonged topical steroid therapy on the kinetics of ECP liberation after
      allergen challenge. These studies will ultimately lead to a more clear definition
      of the clinical usefulness of this procedure.

PMID- 9631692
TI  - [Nose and sinus: anatomo-pathologic relations].
AB  - The relationship between rhinitis and chronic sinusitis is close and complex and
      may perhaps show many points of view, anatomical and physiological,
      epidemiological (by comparing the prevalence of an ailment in carriers of another
      ailment), experimental (by making nasal allergen provocation tests and studying
      the sinus anomalies induced) and physiopathological (by phenotyping and
      comparison of the inflammation present with one another and other ailments). If
      the results of these studies are convincing, there is still lack of formal proof
      that confirms the fundamental role of nasal inflammation in general and in
      particular allergic inflammation in the genesis of sinusitis.

PMID- 9631693
TI  - [Asthma and aspirin].
AB  - Aspirin was discovered by Gerhardt in 1853. The first signs of problems in the
      form of asthmatiform dyspnoea were described in 1911 by Gilbert, then Reed and
      Cookes. Fernand Widal described the symptomatic triad characteristic of "aspirin
      illness" in 1922 with the association of "nasal polyposis, severe asthma and
      aspirin intolerance". It was in 1975 that the role of inhibition of cyclo
      oxygenase was emphasized in physiological interpretation of the illness. Since
      then, very important progress has been made not only in the analysis of the
      affection, but also in its control not only by a new approach to "nose-bronchus"
      relationship which have enabled development of a new strategy in the "ORL and
      pneumologists". If the methods of immuno-allergological investigations, and
      especially scanning imagery and endoscopy, have made possible a better control of
      "aspirin illness" it still remains that this last often remains corticosteroid
      dependent. Important progress is expected with the discovery of anti-leucotrienes
      and several groups have shown the value of anti-leucotrienes in the management of
      "aspirin illness" so leading to the hope that one day there will be a reduction
      in the efficient limiting dose of corticosteroids.

PMID- 9631694
TI  - [HIV infection: DuPont Pharma presents the results of its antiretroviral agent].

PMID- 9631695
TI  - Acute corneal lesion in a German shepherd dog.

PMID- 9631696
TI  - Use of clomipramine in the treatment of anxiety-related and obsessive-compulsive
      disorders in cats.
AB  - OBJECTIVE: To evaluate the efficacy and tolerance of a treatment protocol for
      anxiety-related and obsessive-compulsive disorders in cats. DESIGN: A study was
      undertaken to assess the clinical response in cats diagnosed with anxiety-related
      or obsessive-compulsive disorders to a treatment regimen that included
      clomipramine and behaviour modification. PROCEDURE: The study group of 11 cats
      was acquired through referral. A detailed behavioural and clinical history was
      obtained. Presenting signs were urine spraying in seven cases, overgrooming in
      three and excessive vocalisation in one. Clomipramine was administered orally
      once daily. The mean starting dose was 0.4 mg/kg. If necessary, the dose was
      adjusted according to the clinical response of each cat. A behaviour modification
      program was designed and the owner instructed on its implementation. Cats were to
      continue on medication for at least 1 month after clinical signs disappeared,
      then medication withdrawal was to be attempted by decreasing the clomipramine
      dose progressively at weekly intervals while the behaviour modification program
      continued. RESULTS: In all cases the presenting clinical sign was largely
      improved or disappeared. One cat was removed from the study by the owner. Four
      cats became lethargic at higher doses, but this resolved when the clomipramine
      dose was reduced. The average maintenance dosage was 0.3 mg/kg once daily.
      Clomipramine withdrawal was attempted in two cases: the behaviour returned in one
      case and the medication was reinstated at 0.3 mg/kg twice daily. CONCLUSION:
      Clomipramine was effective in controlling the signs of anxiety-related and
      obsessive-compulsive disorders in 10 of 10 assessable cases when used in
      combination with behaviour modification. Clomipramine was well tolerated.

PMID- 9631697
TI  - Horner's syndrome secondary to metastatic squamous cell carcinoma of a
      retropharyngeal lymph node in a cat.

PMID- 9631698
TI  - Treatment and control by vaccination of erysipelas in farmed emus (Dromaius
      novohollandiae).
AB  - OBJECTIVE: To study erysipelas in farmed emus and the treatment and control of
      the disease by vaccination. DESIGN: A retrospective study of field outbreaks in
      emus and challenge experiments in mice using field and vaccine strains of the
      organism. PROCEDURE: Outbreaks of the disease were described. Field strains of
      the organism were identified and tested by challenge experiments in mice against
      commercial vaccine strains. RESULTS: Erysipelas was characterised by sudden death
      in yearling emus. Deaths mainly occurred during the cold wet months. Mortalities
      of 6 to 10% were seen within the first 7 to 10 days of an outbreak. Clinical
      signs were uncommon but some birds exhibited lethargy and greenish diarrhoea.
      Necropsy findings included marked petechial haemorrhages on the serosal surface
      of the large intestine in particular, pericardial effusion and congestion and
      mottling of the liver. Treatment consisted of individual or mass medication with
      procaine penicillin, reduction of stress factors such as overcrowding, and
      spelling and rotation of paddocks. Isolates from two field outbreaks were
      identified as strain 21. Complete protection was provided by a commercial strain
      2b vaccine against challenge by strain 21 field isolates in mice. Annual
      vaccination of birds at 4 weeks and again at 8 weeks of age appeared to control
      further outbreaks on farms where the disease had previously occurred and
      vaccination appeared to protect for at least 12 months.

PMID- 9631699
TI  - Subchondral cystic lesions involving the second phalanx in two horses.

PMID- 9631700
TI  - Support for writers.

PMID- 9631701
TI  - Efficacy of moxidectin and other anthelmintics against small strongyles in
      horses.
AB  - OBJECTIVE: To compare the efficacy of moxidectin to ivermectin, oxibendazole and
      morantel against some gastrointestinal nematodes in horses. DESIGN: Faecal egg
      count reduction after treatment. PROCEDURE: A farm was selected where the
      population of small strongyles in horses was known to be resistant to
      oxibendazole. Horses were allocated to treatment groups based on faecal egg
      counts. After treatment, faecal samples were taken up to 109 days after treatment
      and faecal egg counts estimated. Faecal cultures were used to estimate the
      contribution of small and large strongyles to the faecal egg counts at each
      sampling. RESULTS: Moxidectin (0.4 mg/kg) suppressed faecal egg counts for 109
      days after treatment in most horses compared to 40 days with ivermectin (0.2
      mg/kg), 13 days with morantel (9.4 mg/kg) and less than 13 days with oxibendazole
      (10 mg/kg). Most of the faecal egg count was attributable to small strongyles
      based on faecal culture, although Strongylus vulgaris was present in some samples
      in low numbers. Oxibendazole resistance in small strongyles was confirmed and a
      less than expected efficacy of morantel was also seen. CONCLUSION: Moxidectin was
      highly effective in reducing faecal egg counts after treatment for at least 12
      weeks and up to 16 weeks in most horses. These horses were infected with a
      population of small strongyles known to be resistant to oxibendazole and possibly
      morantel. The duration of the reduction in faecal egg counts after treatment with
      moxidectin (0.4 mg/kg) was at least twice that of ivermectin (0.2 mg/kg) and
      greater than four times that for morantel and oxibendazole.

PMID- 9631702
TI  - Antibiotics for the preservation of koala (Phascolarctos cinereus) semen.
AB  - AIM: To determine the normal microbial flora of the koala ejaculate and prepuce
      in order to select appropriate antibiotics for addition into diluents designed
      for the preservation of semen. PROCEDURE: Bacteriological samples of the koala
      prepuce (n = 12) and ejaculate (n = 20) were submitted for microbial culture and
      sensitivity testing. Microbial flora of ejaculates collected by
      electroejaculation and artificial vagina were compared. The effects of varying
      concentrations of penicillin G and gentamicin on sperm motility and on the growth
      of bacteria in diluted semen stored at room temperature and 16 degrees C over a
      24 h period were investigated. RESULTS: A range of bacteria was isolated from the
      koala prepuce and ejaculate. The predominant organisms in semen collected by
      electroejaculation and artificial vagina were Corynebacterium spp, none of which
      could be assigned to any recognised species. The addition of penicillin G and
      gentamicin to a PBS-based diluent at dose rates of 1000 to 2000 IU/mL and 100 to
      200 micrograms/mL respectively, resulted in no adverse effect on sperm motility
      over a 24 h incubation period. Penicillin G (1000 IU/mL) and gentamicin (100
      micrograms/mL) prevented growth of bacterial contaminants in diluted koala semen.
      CONCLUSION: By controlling the growth of bacteria in extended koala semen,
      penicillin G and gentamicin are likely to lengthen the period by which
      spermatozoa can be stored at 16 degrees C and reduce the possibility of disease
      transmission during artificial insemination procedures.

PMID- 9631703
TI  - Effects of two large doses of equine recombinant growth hormone on clinical,
      haematological and serum biochemical variables in adult horses.
AB  - OBJECTIVE: To evaluate the clinical, haematological, and serum biochemical
      effects of two large doses of recombinant equine growth hormone. DESIGN:
      Duplicated Latin square. SAMPLE POPULATION: Three Thoroughbred and three
      Standardbred mares aged between 12 and 17 years. PROCEDURE: Two horses were
      randomly assigned into one of three groups. On each of three successive days,
      each horse pair received one of two dosages of growth hormone or a saline placebo
      so that by the end of the experiment all three horse pairs had received both
      dosages and the saline placebo. Dose rates selected were 50 micrograms/kg, and
      100 micrograms/kg. A clinical examination was performed and a venous blood sample
      drawn for a complete blood count and serum biochemical analysis before
      administration of growth hormone and at 1, 2, 3, 4, 6, 8 and 24 h after
      injection. Data were analysed by a repeated measures analysis of variance
      assessing the effects of dose and time. RESULTS: There was an effect of time on a
      number of clinical, haematological, and serum biochemical variables. There were
      significant effects of growth hormone on heart rate and serum glucose
      concentration but values for both variables remained within the reference range.
      CONCLUSION: The results of the present study suggest that equine recombinant
      growth hormone has a wide margin of safety and show that the single
      administration of up to five times the recommended dose rate has no significant
      effects on clinical, haematological, or serum biochemical variables.

PMID- 9631704
TI  - Effectiveness of a mixture of cyromazine and diazinon for controlling flystrike
      on sheep.
AB  - OBJECTIVE: To determine whether there is any need for woolgrowers to add diazinon
      to cyromazine jetting fluid to control active flystrike on sheep. METHOD: Larval
      implants were placed on 143 sheep and allowed to develop for 2 days. Groups of 47
      or 48 of these struck sheep were jetted with cyromazine at 1000 mg/L, diazinon at
      400 mg/L, or a mixture of the two. After treatment, the implants were assessed
      daily for 3 days for the presence of feeding larvae. RESULTS: When checked 1 day
      after treatment, there was a 62% reduction in flystrike in the diazinon treated
      sheep compared to only 12% reduction on the cyromazine treated sheep. Flystrike
      reduction on the sheep jetted with the mixture of cyromazine and diazinon was
      69%. Three days after treatment flystrike control was 97 to 99% in the latter two
      groups. CONCLUSION: Diazinon provided a faster resolution of strikes but by 3
      days after treatment there was no significant difference in the number of
      implants remaining active on the sheep treated with cyromazine or with the
      mixture of cyromazine and diazinon.

PMID- 9631705
TI  - Molybdenum poisoning in feedlot cattle.
AB  - OBJECTIVE: To describe a case of acute, fatal molybdenum poisoning in feedlot
      cattle. DESCRIPTION OF THE HERD: In total, 831 Hereford, Hereford x Angus, and
      Hereford x Simmental steers, aged 8 to 10 months, with an average body weight of
      310 kg were fed a diet, to which sodium molybdate at a rate of 1.9% of the total
      ration had been accidently added. INVESTIGATION: The steers lost appetite within
      3 days and deaths commenced within 6 days of the diet being first offered. The
      error was rectified when deaths started to occur, but steers continued to die for
      up to 7 months afterwards. Of the 831 steers on the feedlot, 90 died and a
      further 5 remained in poor condition. The cause of death was periacinar to
      massive hepatic necrosis and acute renal tubular necrosis. Blood and tissue
      samples were taken from surviving steers for 76 days, by which time plasma
      molybdenum concentrations had returned to normal concentrations. CONCLUSION:
      Sodium molybdate when fed at a rate of 1.9% of the diet results in acute renal
      tubular necrosis and periacinar to massive hepatic necrosis.

PMID- 9631706
TI  - Efficacy of ivermectin in a controlled-release capsule for the control of breech
      strike in sheep.
AB  - OBJECTIVE: To investigate the efficacy of ivermectin in an intraruminal
      controlled-release capsule (CRC) against blowfly strike. DESIGN: Pen and field
      trials with controls. ANIMALS: Pen studies: Two breech strike trials involving 60
      Romney and 60 Merino sheep. One body strike trial using 100 Merino sheep. Field
      trials: Eight trials in New Zealand used 1000 Romney and Romney-cross sheep.
      Fifty Merino lambs in one trial in Australia. PROCEDURE: Pen studies: Sheep were
      allocated to two equal groups. One was not treated, the other sheep received a
      CRC that delivered ivermectin at > or = 20 micrograms/kg/day for 100 days. In the
      breech strike trials, each animal was given an oral laxative 2 days before
      exposure to adult Lucilia cuprina. In the body-strike trial, the sheep sheep were
      kept wet to increase susceptibility prior to the release of blowflies. Field
      trials: Fifty or 200 sheep allocated to equal groups of nontreated or treated
      with the CRC and grazed at pasture exposed to natural blowfly challenge. RESULTS:
      Pen studies: Breech strikes developed in 24 of 60 controls but in none of 60 CRC
      treated sheep. There was a 35% reduction in the number of CRC-treated sheep
      struck on the body. Field trials: The average number of breech strikes in CRC
      treated sheep was reduced by 86% (P < 0.001). The number of body strikes in the
      treated groups was a reduced by 27% (P < 0.05). CONCLUSION: The ivermectin CRC is
      a useful aid in controlling breech strike, but provides only moderate reduction
      in the incidence of body strike.

PMID- 9631707
TI  - Combination of zolazepam and tiletamine as a sedative and anaesthetic for
      wombats.
AB  - OBJECTIVE: To assess the suitability of the combination of zolazepam and
      tiletamine for routine use as chemical restraint, sedative and anaesthetic in
      wild wombats. ANIMALS: Sixty common wombats, 25 southern hairy-nosed wombats and
      40 northern hairy-nosed wombats. PROCEDURE: Wombats caught in cage-traps in the
      wild were given injections of the anaesthetic combination either intramuscularly
      or intraperitoneally. Anaesthesia was maintained for up to 4 h in some cases, and
      for 12 h in one case. All wombats were released after anaesthesia. RESULTS AND
      CONCLUSION: This drug combination is effective and apparently safe for the
      sedation or light anaesthesia of wombats. We did not observe adverse reactions or
      deaths and the dose range used (4 to 15 mg/kg) demonstrates a wide safety margin.
      The use of this anaesthetic combination was effective in reducing the stress to
      wombats from capture and handling.

PMID- 9631708
TI  - Pathology of skin diseases in crocodiles.
AB  - OBJECTIVE: To establish which skin diseases occur in crocodiles, particularly
      those on farms, to indicate the relative frequency of each particular disease and
      to provide information on pathogenesis, especially in regard to lesions with two
      or more pathogens present. DESIGN: A gross and microscopic retrospective (period
      of 1989 to 1995) and current (1996 to 1997) examination of skin lesions in
      crocodiles in Queensland and the Northern Territory. RESULT: Skin lesions were
      obtained from crocodiles on nine farms, from a group of experimental animals and
      from one adult found dead in the wild. A total of 203 lesions from 180, mostly
      young, crocodiles was examined; 119 lesions were from retrospectively examined
      cases and 84 were recent. The relative frequencies of four presumed primary
      pathogens in lesions were Dermatophilus sp 28.1%, fungi 14.8%, poxvirus 3.4% and
      probable Mycobacterium sp 2.5%. In addition, other bacteria of unknown
      significance were present in many lesions, and there was one case of presumed
      Paratrichosoma crocodilus infection. In 32.5% of lesions, multiple pathogens were
      identified. CONCLUSION: Dermatophilosis is the most common and probably the most
      important skin disease of crocodiles in Australia, but it is frequently
      complicated by concurrent infection with fungi or other microorganisms.

PMID- 9631709
TI  - Isolation of verocytotoxin-producing Escherichia coli from mutton carcases.

PMID- 9631711
TI  - [Delayed locomotor stereotypes and psychoaffective disturbances in rats after
      rhythmic electric stimulation of the sensomotor cortex of the right cerebral
      hemisphere].

PMID- 9631710
TI  - [Heart lysosomes and the mechanism of ouabain effect].

PMID- 9631713
TI  - [Effect of stimulation of M-cholinoreceptors on noradrenaline accumulation in the
      esophageal and gastric mucosa of rats].

PMID- 9631712
TI  - [The role of SC-1(+)- and Thy-1(+)-cells in the regulation of cytokine production
      by cells of the bone marrow regenerating after cytostatic action].

PMID- 9631714
TI  - [Nitric oxide donor increases and NO synthase blocker decreases the body ability
      to carry out and adapt to a heavy physical load].

PMID- 9631715
TI  - [Effect of multiple cold stress on the intensity of lipid peroxidation and tissue
      antioxidant system].

PMID- 9631716
TI  - [Study of mass transfer in the blocked rabbit artery in vivo].

PMID- 9631717
TI  - [Approaches to predicting the limits of body resistance to hypoxia based on
      assessment of adenine nucleotide system].

PMID- 9631718
TI  - [Effect of alimentary hypercholesterolemia in female rabbits on the blood lipid
      levels in their offspring].

PMID- 9631719
TI  - [Effect of S-adenosylmethionine, ethanolamine, and their combination on the lipid
      composition in the rat brain during chronic alcoholic intoxication].

PMID- 9631720
TI  - [Effect of intranasal administration of gamma-aminobutyric acid on intraspecies
      aggression in male mice].

PMID- 9631721
TI  - [Effect of befol and sufan on the neurogenic atrial fibrillation].

PMID- 9631722
TI  - [Behavioral and electrophysiologic analysis of the anxiolytic effect of
      astragalus mongolian].

PMID- 9631723
TI  - [Protective effects of trimetazidine during acute hypoxia].

PMID- 9631724
TI  - [Serotoninergic mechanism of dependence of neurotropic properties of lithium
      hydroxybutyrate on circadian phase of its administration].

PMID- 9631725
TI  - [Pharmacologic regulation of hepatocyte cytolysis by antioxidants during acute D
      galactosamine hydrochloride intoxication].

PMID- 9631726
TI  - [Characteristics of behavior of rats with the different genetic resistance to
      stress].

PMID- 9631727
TI  - [Mechanism of the anti-arrhythmic effect of Rhodiola rosea extract].

PMID- 9631728
TI  - [Autoantibodies similar to anti-differential ones in immune neutropenia].

PMID- 9631729
TI  - [Participation of galaninergic brain structures in response to the systemic
      lipopolysaccharide administration].

PMID- 9631730
TI  - [Lymphocyte apoptosis--one of mechanisms of specific immunotherapy of atopic
      diseases].

PMID- 9631731
TI  - [Comparative study of the antineoplastic cytostatic and natural suppressive
      activity of bone marrow cells].

PMID- 9631732
TI  - [Identification and characteristics of new systems of genetic plasmid transfer
      regulation].

PMID- 9631733
TI  - [Functioning of the hypophyseal-adrenocortical system in rats selected for the
      sensitivity threshold to the electric current].

PMID- 9631734
TI  - [Sex steroid-binding globulin in serum of children with psoriasis].

PMID- 9631735
TI  - [Importance of the adenylate cyclase liver system for development of its chronic
      damage].

PMID- 9631737
TI  - [Age characteristics of formation of the hematopoietic microenvironment by
      stromal progenitors from the bone marrow of thymectomized mice].

PMID- 9631736
TI  - [Study of the combined action of vibration and chemical mutagens in the
      micronucleus test].

PMID- 9631738
TI  - [Structure-functional morphology of the liver acute phase reaction during
      experimental hypercholesterolemia].

PMID- 9631739
TI  - [Effect of calcium antagonists on the kidney transplant damage during prolonged
      cold ischemia].

PMID- 9631740
TI  - [Characteristics of response of different functional zones of the thymus and
      spleen lymphoid tissue to gamma-radiation in mice].

PMID- 9631741
TI  - [Biologic availability of endogenous rat calcitonin].

PMID- 9631742
TI  - [New method of modeling of experimental hepatic echinococcosis].

PMID- 9631743
TI  - Mast cells in rheumatic disorders: mastermind or workhorse?

PMID- 9631744
TI  - Is it lupus? The St. Thomas' Hospital "alternative" criteria.

PMID- 9631745
TI  - Long-term prostacyclin reduces pulmonary vascular resistance in severe primary
      pulmonary hypertension.

PMID- 9631746
TI  - Enhanced neutrophil and eosinophil adhesion in patients with primary Sjogren's
      syndrome.
AB  - OBJECTIVE: To study granulocyte adhesion to E-selectin, VCAM-1 and ICAM-1 in
      patients with primary Sjogren's syndrome (pSS). In previous studies diminished
      neutrophil adhesion has been shown as measured by the nylon fiber method.
      METHODS: Neutrophil and eosinophil adhesion to the adhesion molecules E-selectin,
      VCAM-1 and ICAM-1 were measured using transfected fibroblasts. The cell surface
      expression of the integrin proteins CD11a, CD11b, CD18 and CD29 on neutrophils
      was assayed by means of flow cytometry. RESULTS: Neutrophils and eosinophils from
      patients with pSS had elevated basal adhesion in the presence of Mn2+ as compared
      with controls (basal adhesion was considered to be the adhesion to untransfected
      fibroblasts). Granulocyte adhesion to E-selectin was also elevated. No
      differences were seen between patients and controls in cell surface expression of
      the integrin proteins CD11a, CD11b, CD18 and CD29 on neutrophils, nor was there
      any difference in these parameters between patients with and without extra
      glandular symptoms. CONCLUSIONS: These results suggest that blood neutrophils and
      eosinophils are activated in pSS. Accordingly they do not confirm results from
      earlier studies of impaired neutrophil adhesion in pSS.

PMID- 9631747
TI  - Elevated serum concentrations of the chemokine RANTES in patients with
      polymyalgia rheumatica.
AB  - OBJECTIVE: Evaluation of serum concentrations of chemotactic cytokines
      (chemokines) in patients with polymyalgia rheumatica at disease diagnosis and
      during a six-month period of corticosteroid treatment. METHODS: Sera were
      obtained from patients at the time of PMR diagnosis and subsequently after one
      week, two weeks, one month, three months and six months. At each time point a
      clinical and laboratory evaluation was performed. Serum concentrations of IL-8,
      GRO alpha, RANTES, MCP-1, and MIP1 alpha were evaluated by commercial ELISA kits.
      RESULTS: Only RANTES serum levels were significantly higher in PMR patients than
      in controls. No correlation was found between RANTES concentrations and
      laboratory and clinical features. Chemokine levels reached their lowest level
      after one month of steroid treatment and remained in the normal range thereafter.
      CONCLUSIONS: The production of RANTES is enhanced in untreated PMR patients;
      corticosteroid treatment results in a normalization of chemokine levels.

PMID- 9631748
TI  - Matrix metalloproteinases, IL-6, and nitric oxide in rat antigen-induced
      arthritis.
AB  - OBJECTIVE: Degradation of extracellular matrix by matrix metalloproteinases
      (MMPs) is believed to be important in processes leading to the progressive
      destruction of joints in rheumatoid arthritis (RA). We used the model of antigen
      induced arthritis (AIA) to study MMP activity and the influence of cytokines on
      their expression by synoviocytes. MATERIAL AND METHODS: Procedures used were:
      mBSA-induced arthritis in rats; investigation of synovial fluids and supernatants
      of cultured synoviocytes at different time points during AIA; estimation of total
      MMP activities by fluorescence assay; zymographic investigations; IL-6 bioassay
      with B9 cells; nitric oxide (NO) estimation. RESULTS: Total MMP activity in the
      synovial fluids of arthritic joints was higher than in the contralateral joints
      or in the joints of untreated control animals. The maximum was noted between day
      7 and day 14 after arthritis induction. Cultured synoviocytes, prepared at
      different time points after arthritis induction, secreted MMPs into the media
      with a maximum time lapse of 14 days after arthritis induction. TNF-alpha
      increased the total MMP activity released. Moreover, TNF-alpha as well as IL-1
      beta induced the expression of MMP9. Finally, TNF-alpha increased the levels of
      IL-6 and NO in the supernatants of synoviocytes; the extent of stimulation was
      dependent on the course of AIA. CONCLUSIONS: Different MMPs are synthesized in
      varying concentrations during the course of rat AIA. Cytokines such as TNF-alpha
      and IL-1 beta differentially influence the activity and expression of MMPs in
      cultured synoviocytes. The participation of MMPs in tissue degradation during the
      course of arthritis may be of importance for the development of new therapeutic
      strategies.

PMID- 9631749
TI  - Clinical, laboratory and immunogenetic aspects of post-traumatic psoriatic
      arthritis: a study of 25 patients.
AB  - OBJECTIVE: In a previous study we demonstrated that the prevalence of trauma
      preceding arthritis was higher in patients with psoriatic arthritis (PsA) than in
      patients with rheumatoid arthritis (RA) or ankylosing spondylitis (AS); of 300
      consecutive patients with PsA, 25 (8%) had a history of trauma before (< 3
      months) the onset of the disease. The present study was carried out to
      characterize the clinical, laboratory and immunogenetic profiles of post
      traumatic (PT)-PsA. PATIENTS AND METHODS: The clinical and laboratory features of
      25 patients with PT-PsA were studied at onset (first 6 months) and after a follow
      up period of 1-7 years, and were compared with those of 275 PsA patients without
      any history of trauma (nonPT-PsA). HLA typing was performed in PT-PsA patients,
      and synovial fluid (SF) analysis, including interleukin (IL)-1 and IL-6
      determinations, was carried out in 12 subjects with PT-PsA and in 32 with nonPT
      PsA. RESULTS: No differences were observed between PT-PsA and nonPT-PsA patients
      with regard to their clinical evolution. ESR (p < 0.0001) and CRP (p = 0.005)
      were higher in PT-PsA than in nonPT-PsA patients at disease onset but not after
      follow-up. No differences were found in the other blood indices. SF analysis
      revealed higher IL-6 levels in PT-PsA than in nonPT-PsA patients (p < 0.0005).
      CONCLUSION: Our study demonstrates that the prevalence of trauma preceding
      arthritis is higher in PsA than in RA or AS. Clinical and laboratory findings in
      patients with PT-PsA differed from those with nonPT-PsA only at disease onset
      (first six months), however, showing an abrupt clinical presentation and a more
      acute phase response. This pattern may be related to the higher levels of IL-6
      found in the SF of PT-PsA than in nonPT-PsA patients. However, during the follow
      up period the two groups became indistinguishable, and no difference was observed
      between PT-PsA and nonPT-PsA regarding the evolution of the disease.

PMID- 9631750
TI  - Elevated interleukin-10 levels correlated with disease activity in systemic lupus
      erythematosus.
AB  - OBJECTIVE: To determine serum interleukin-10 (IL-10) levels in systemic lupus
      erythematosus (SLE) patients and to assess their relationship with disease
      activity. METHODS: Forty-one SLE patients and 35 controls were studied. Paired
      serum samples were collected from all SLE patients at the time of their
      presentation with active disease and at 4 weeks after the institution of
      treatment. IL-10 levels were determined in the sera and were compared with
      disease activity, measured using the SLE Disease Activity Index (SLEDAI) and
      laboratory parameters such as the circulating immune complexes (CIC), C3, C4,
      anti-DNA antibody, IgG, IgM, and IgA. RESULTS: The IL-10 levels in SLE patients
      were significantly higher than those of controls (mean +/- SE, 29.2 +/- 6.8 vs.
      3.5 +/- 0.6 pg/ml, p < 0.01). Elevated IL-10 levels correlated well with the
      SLEDAI in SLE patients (r = 0.46, p < 0.01), but did not correlate with other
      laboratory activity indices. The changes in serum IL-10 levels also correlated
      with the changes in the SLEDAI score during the patients' disease course (r =
      0.51, p < 0.01). CONCLUSION: Serum levels of IL-10 are elevated in SLE patients
      and increased IL-10 correlates well with SLE disease activity.

PMID- 9631751
TI  - Potential role of the Epstein-Barr virus in systemic lupus erythematosus
      autoimmunity.
AB  - OBJECTIVE: To investigate the possibility that Epstein-Barr virus (EBV), the
      agent of infectious mononucleosis (IM), may play a role in systemic lupus
      erythematosus (SLE). METHODS: EBV was searched for by PCR and by culture
      isolation in oropharyngeal lavage fluids of 15 SLE patients and, as controls, in
      13 IM patients and in 28 healthy individuals with past EBV infection. Computer
      analysis was performed to select an antigenic domain of the virus-encoded nuclear
      antigen EBNA-2, in order to set up a synthetic peptide-based immunoassay. IgG
      antibodies to a 20-amino acid synthetic peptide derived from the selected domain
      of EBNA-2 (354GRGKGKSRDKQRKPGGPWRP373) were titrated in the sera of 20 SLE
      patients, 24 IM patients and 12 healthy subjects. RESULTS: EBV type 1 DNA was
      demonstrated by PCR in the oropharyngeal secretions of 8 SLE patients and the
      virus was isolated from 6 DNA-positive specimens. Moreover, 50% of the patients
      with SLE and 100% of the patients in the acute phase of IM, but none of the EBV
      seropositive normal individuals, produced IgG antibodies to the EBNA-2-derived
      synthetic peptide. Computer analysis revealed a high degree of homology between
      the EBNA-2 354GRGKGKSRDKQRKPGGPWRP373 sub-sequence and the antigenic C-terminal
      domain 101GRGRGRGRGRGRGRGGPRR119 of the SmD1 ribonucleoprotein, a target of
      autoantibodies in a portion of SLE patients. CONCLUSION: We suggest the
      possibility that EBV may establish a persistent infection at least in a certain
      number of SLE patients. The antibodies elicited by the viral antigen EBNA-2 may
      cross-react with SmD1, thus indicating a role of EBV-specific immune responses in
      the outcome of SmD1 autoantibodies in SLE patients.

PMID- 9631752
TI  - Intravenous immunoglobulin in adult Still's disease refractory to non-steroidal
      anti-inflammatory drugs.
AB  - OBJECTIVE: Adult onset Still's disease (AOSD) is a systemic disorder with an
      uncertain outcome at the time of diagnosis. The clinical response to nonsteroidal
      antiinflammatory drugs (NSAIDs) is often unsatisfactory in adult patients.
      Chronic use of steroids is frequently required, but may result in severe side
      effects. We report the results of an uncontrolled, unblinded trial of intravenous
      immunoglobulin (IVIG) in 7 patients with AOSD. METHODS: Seven consecutive
      patients unresponsive or poorly responsive to NSAIDs were enrolled. None of them
      had received steroids previously. AOSD was defined by the Yamaguchi criteria (J
      Rheumatol 1992; 19: 424). IVIG were administered every 4 weeks. NSAIDs were
      initially maintained. A positive response was defined by the disappearance of
      fever and arthritis within 2 weeks after the first IVIG infusion. RESULTS: Two
      patients failed to respond. Five patients initially considered to be good
      responders were given a total of 4 to 6 IVIG infusions. One of them relapsed at
      the time of the fourth IVIG infusion. The four others had a favourable clinical
      and biological course. At the time of evaluation 3 patients were symptom-free and
      off therapy, while one was still receiving low dose NSAIDs. CONCLUSION: This
      short, uncontrolled, unblinded study suggests that IVIG might represent a
      potential alternative to classical steroid therapy in patients with AOSD
      refractory to NSAIDs. These preliminary results need to be confirmed, however, in
      a double-blind randomized study.

PMID- 9631753
TI  - Long-term effects of amyloid enhancing factor: clinical and experimental
      implications.
AB  - OBJECTIVE: To study the long-term effects of amyloid enhancing factor (AEF).
      METHODS: AEF, prepared from pre-amyloidotic mouse spleens, was injected
      intravenously into Swiss and ICR mice. This was followed by 3 daily subcutaneous
      injections of AgNO3, given at increasing time intervals from the administration
      of AEF. The mice were sacrificed on day 6 from the first AgNO3 injection, and the
      mean grade of amyloid deposition in the spleens was estimated using the crush and
      smear technique. RESULTS: AEF was found to have a prolonged enhancing effect,
      retaining its activity for more than 3 months after its administration in both
      mouse strains. CONCLUSIONS: Experimental animals may develop amyloidosis long
      time after exposure to AEF. This finding may underlie the acute reoccurrence of
      amyloidosis sometimes observed in patients and mice long after its resolution.

PMID- 9631754
TI  - Rheumatic manifestations in the course of anaphylaxis caused by Anisakis simplex.
AB  - Human anisakidosis is a parasitic infection caused by the larvae of Anisakis
      simplex. Classical clinical manifestations include epigastric pain, occlusion,
      diffuse abdominal pain, appendicitis, and anaphylactoid reactions. Arthralgias or
      arthritis have been infrequently reported. We present three patients with proven
      hypersensitivity to A. simplex together with rheumatologic complaints after
      ingestion of parasitized fishes. A. simplex must be considered in the
      differential diagnosis of arthralgias/ arthritis especially if associated with
      urticaria.

PMID- 9631755
TI  - Tuberculous spondylitis as a cause of inflammatory spinal pain: a report of 4
      cases.
AB  - Patients are said to have inflammatory spinal pain if they fulfill at
      presentation 4 of the following 5 criteria: duration of spinal discomfort for at
      least 3 months, spinal morning stiffness, age less than 40, insidious onset of
      symptoms, and no relief from pain with rest, but improvement with exercise.
      Inflammatory spinal pain is typical of the spondylarthropathies. Only in a
      minority of the cases it is found in other rheumatic disorders such as rheumatoid
      arthritis, fibromyalgia or infectious spondyilitis. Tuberculous spondylitis is
      rarely mentioned as a possible cause of inflammatory spinal pain. We describe 4
      patients with tuberculous spondylitis seen over a 3-year period who met the
      clinical criteria for inflammatory spinal pain at presentation. We conclude that
      inflammatory spinal pain may be a presenting feature, albeit rare, of tuberculous
      spondylitis. Awareness of this finding should help facilitate the proper
      diagnosis and the institution of appropriate therapy.

PMID- 9631756
TI  - Chronic lower back pain due to sarcoma.
AB  - We describe a 74-year-old woman with extensive pelvic leiomyosarcoma presenting
      with uncharacteristic musculoskeletal pain of the lumbosacral region and left
      lower extremity. Hemipelvectomy was considered the treatment of choice, and a
      model for a pelvic prosthesis was constructed based on imaging analysis. However,
      the tumour (and the complaints) responded surprisingly well to a combined
      treatment regimen including superselective arterial catheter embolization, which
      led to tumour regression to such a degree that aggressive surgical treatment
      became unnecessary.

PMID- 9631757
TI  - Progressive multifocal leukoencephalopathy resembling central nervous system
      systemic lupus erythematosus.
AB  - A 21-year-old woman with a 6-year history of SLE presented with a speech
      disturbance and right hand clumsiness along with manifestations of active disease
      suggesting central nervous system SLE. Despite aggressive treatment for SLE, her
      neurological condition worsened. MRI demonstrated low intensity in T1-weighted
      images and high intensity in T2-weighted images in the white matter of the
      bilateral cerebrum and cerebellum, compatible with progressive multifocal
      leukoencephalopathy (PML). Intraspinal administration of interferon-beta seemed
      to slow the deterioration of her MRI and neurological findings. However, she
      eventually developed decerebrate rigidity and died due to candidemia. DNA of the
      JC virus was detected in the autopsied brain by the polymerase chain reaction
      technique. PML should always be borne in mind when examining patients with SLE
      showing neurological abnormalities.

PMID- 9631758
TI  - Heterogeneous nuclear ribonucleoproteins (hnRNPs): an emerging family of
      autoantigens in rheumatic diseases.
AB  - In eukaryotic cells, mature mRNA molecules are produced through the extensive
      post-transcriptional processing of primary transcripts assembled in
      ribonucleoprotein complexes. Twenty polypeptides, termed heterogeneous nuclear
      ribonucleoproteins or hnRNPs, have been identified as the major components of
      such complexes. Although these proteins were identified more than 30 years ago,
      their role in RNA metabolism is just beginning to emerge. In contrast to previous
      models that ascribed to hnRNPs a mere structural function, recent data suggest a
      direct involvement in several aspects of the RNA life, such splicing, export of
      the mature mRNAs to the cell cytoplasm and translation. In addition, a growing
      body of evidence points to hnRNPs as an important target of the autoimmune
      response in rheumatic diseases. The present paper will review some of the most
      relevant data concerning the structure, function and autoantigenic properties of
      the hnRNPs.

PMID- 9631760
TI  - Low-dose methotrexate as a steroid-sparing agent in a child with Takayasu's
      arteritis.
AB  - Takayasu's arteritis (TA) is a chronic inflammatory arteriopathy affecting the
      large vessels and has been described predominantly in young adult women. In
      children it presents as an aggressive disease usually requiring chronic
      corticosteroid therapy. At present, low dose oral methotrexate (MTX) appears to
      be an effective steroid-sparing agent in adult patients with active TA. We report
      a 4-year-old child with Takayasu's arteritis who was initially placed on oral
      prednisone (2 mg/kg/day) therapy. Three months later, low-dose oral MTX (10
      mg/m2/week) was added. Prednisone was successfully tapered over the following
      year to 0.2 mg/kg every other day. A repeat angiography following 12 months of
      therapy revealed a dramatic improvement of the vascular lesions. No toxicity was
      observed with MTX therapy. In conclusion, low-dose oral MTX appeared to be an
      efficient, safe and steroid-sparing agent in the treatment of a young child with
      TA.

PMID- 9631759
TI  - 99mTc-white cell scanning to detect gut inflammation in children with
      inflammatory bowel diseases or spondyloarthropathies.
AB  - OBJECTIVE: Gut inflammation is a common feature shared by inflammatory bowel
      diseases (IBD) and the spondyloarthropathies (SpA). The aim of the present study
      was to compare the reliability of a number of non-invasive investigations for the
      detection of an inflammatory process of the intestine. METHODS: Forty-two
      children were studied: (i) patients with a previous diagnosis of IBD (group A);
      (ii) patients with suspected IBD (group B); and (iii) patients with predominantly
      rheumatological manifestations associated with gastrointestinal symptoms (group
      C). All the patients were studied using 99mTechnetium-HMPAO labelled white cell
      scanning (99mTc-WCS), and abdominal ultrasound (US). In addition the ESR, serum
      class A immunoglobulins, faecal occult blood (OB) and faecal alpha 1-antitripsin
      level (F alpha 1-AT) were determined. Colonoscopy plus multiple biopsies and
      radiological study of the intestine were used as gold standards. RESULTS: 99mTc
      WCS showed the highest sensitivity (85%) and specificity (100%) in detecting the
      presence of gut inflammation. This was followed by ESR and faecal occult blood
      (63% sensitivity, 44% specificity), F alpha 1-AT (43% sensitivity, 44%
      specificity) and IgA (42% sensitivity, 88% specificity). Ultrasound was
      informative in 28% of the active/affected patients, with a specificity of 75%.
      CONCLUSION: Although ileo-pancolonscopy remains the gold standard for the
      histological characterisation of gut inflammation, 99mTc-WCS represents the most
      reliable non-invasive test for its detection.

PMID- 9631761
TI  - Erythema nodosum: a presenting sign of early onset sarcoidosis.
AB  - "Early onset sarcoidosis" is a chronic granulomatous disease occurring in
      children younger than 5 years of age, and characterized by a classic symptom
      triad consisting of skin, eye and joint lesions, with on rare occasion pulmonary
      involvement. The disorder often goes unrecognized because of its rarity and,
      since polyarthritis and uveitis are the predominant symptoms, most of these
      children are misdiagnosed as having juvenile chronic arthritis (JCA). A child
      with erythema nodosum at 7 months of age, later diagnosed as JCA and definitively
      recognized as "early onset sarcoidosis" is reported. This case shows that,
      whenever possible, a biopsy showing the typical picture of sarcoid granulomas is
      crucial to distinguish these clinical conditions.

PMID- 9631762
TI  - The discovery of the rheumatoid factor. I. Erik Waaler. 1940.

PMID- 9631763
TI  - The discovery of the rheumatoid factor. II. Rose, Ragan, Pearce & Lipman. 1948.

PMID- 9631765
TI  - Antiphospholipid antibodies and Raynaud's phenomenon in rheumatoid arthritis.

PMID- 9631764
TI  - The impact of life events on patients with rheumatoid arthritis.

PMID- 9631766
TI  - Extremely low dose treatment of cyclosporine for autoimmune diseases.

PMID- 9631767
TI  - Polyglandalar autoimmune syndrome type II and rheumatoid arthritis.

PMID- 9631768
TI  - CPT coding and Medicare reimbursement: from beans to bullets.

PMID- 9631769
TI  - E&M guidelines: Is the medical record a database repository or a communication
      tool?

PMID- 9631770
TI  - The United States and worldwide tuberculosis control: a second chance for Prince
      Prospero.

PMID- 9631771
TI  - Pulmonary arterial hypertension: dipping into the reserve.

PMID- 9631772
TI  - Physiology of lung resection: no rules, just...Rx.

PMID- 9631773
TI  - Sherlock Holmes, Albrecht Durer, and Socrates: The International Labour Office
      radiographic Classification of Pneumoconioses reassessed for asbestosis.

PMID- 9631774
TI  - The uncertain value of the definition for SIRS. Systemic inflammatory response
      syndrome.

PMID- 9631775
TI  - The diagnostic strategy for Pneumocystis carinii pneumonia: is doing less better
      than doing more?

PMID- 9631776
TI  - Initial drug regimens for the treatment of tuberculosis: evaluation of physician
      prescribing practices in New Jersey, 1994 to 1995.
AB  - STUDY OBJECTIVE: To evaluate physician prescribing practices for the initial
      therapy for tuberculosis (TB) according to the recommendations of the Centers for
      Disease Control and Prevention (CDC) and American Thoracic Society (ATS). DESIGN:
      Cross-sectional study. SETTING: Statewide TB surveillance system in New Jersey,
      1994 to 1995. PATIENTS: We studied 1,230 culture-positive TB patients who were
      alive at diagnosis and whose isolates were tested for isoniazid susceptibility.
      RESULTS: Almost all TB patients (98%) were reported from counties with an
      isoniazid-resistant proportion of 4% or more, which is the minimum level for
      implementation of an initial four-drug regimen recommended by CDC/ATS. Overall,
      36% of the 1,230 patients were not initially treated with four or more drugs.
      Multivariate analyses found that non-Hispanic white patients were more likely to
      be treated with fewer than four drugs than were non-Hispanic black patients.
      Private practitioners and physicians at chest clinics were about five times more
      likely to prescribe fewer than four drugs initially than were physicians at the
      hospital where a national TB center is located. CONCLUSION: A substantial
      proportion of physicians did not initially treat their TB patients according to
      the CDC/ATS recommendations. The results suggest that New Jersey physicians
      should be better informed about the recommendation and the high level of drug
      resistance in the communities they serve to assure that TB patients receive
      appropriate initial therapy.

PMID- 9631777
TI  - Epidemiology and clinical consequences of drug-resistant tuberculosis in a
      Guatemalan hospital.
AB  - STUDY OBJECTIVE: To determine the epidemiology and clinical consequences of drug
      resistant TB in Guatemala. DESIGN: A prospective study conducted for 12 months.
      SETTING: A thoracic referral hospital in western Guatemala. PATIENTS: Three
      hundred and seventy-six patients with confirmed TB. RESULTS: Of 376 confirmed
      cases, 335 (89%) were culture-positive. Tests of drug sensitivities to four first
      line antituberculous drugs were performed in 172 (51%) of the culture-positive
      cases. Fifty-one patients (30%) were resistant to at least one antimicrobial
      agent, and 26 (15%) were resistant to at least two drugs. In a multivariate model
      of clinically available patient characteristics, only cavitary disease (odds
      ratio=2.1; 95% confidence interval, 1.1-6.6) and a history of taking anti-TB
      medication for >2 weeks (OR=3.0; 95% CI, 1.5-10.3) were independent predictors of
      resistance to two or more anti-TB agents. Resistance to two or more anti-TB drugs
      was the single independent predictor of treatment failure (OR=6.4; 95% CI, 2.3
      17.8). Twenty-four of 172 patients (14%) who denied having received prior anti-TB
      therapy were infected with resistant organisms, suggesting ongoing transmission
      of drug-resistant strains. Although 84% (69 of 82 cases) of patients with fully
      susceptible organisms and 89% (17 of 19 cases) with singly resistant organisms
      were cured, only 45% of patients (10 of 22 cases) infected with organisms
      resistant to two or more agents were successfully treated. CONCLUSIONS: At this
      sentinel site for complicated TB, a substantial subset of cases who are infected
      with drug-resistant bacteria cannot be easily identified or treated.

PMID- 9631778
TI  - Evaluation of right ventricular systolic pressure during incremental exercise by
      Doppler echocardiography in adults with atrial septal defect.
AB  - STUDY OBJECTIVES: Pulmonary hypertension is the most important complication in
      patients with atrial septal defect (ASD), but its role in limiting exercise has
      not been examined. This study sought to evaluate exercise performance in adults
      with ASD and determine the contribution of elevated pulmonary artery pressure in
      limiting exercise capacity. DESIGN: We used Doppler echocardiography during
      exercise in 10 adults (aged 34 to 70 years) with isolated ASD (New York Heart
      Association class I, II) and an equal number of matched control subjects.
      Incremental exercise was performed on an electrically braked upright cycle
      ergometer. Expired gases and VE were measured breath-by-breath. Two-dimensional
      and Doppler echocardiographic images were obtained at rest prior to exercise to
      determine ASD size, stroke volume (SV), shunt ratio (Qp:Qs), right ventricular
      outflow tract (RVOT) size, and right ventricular systolic pressure at rest
      (RVSPr). Doppler echocardiography was repeated at peak exercise to measure right
      ventricular systolic pressure during exercise (RVSPex). RESULTS: Resting
      echocardiography revealed that RVOT was larger (21+/-4 vs 35+/-8 mm, mean+/-SD;
      p=0.0009) and RVSPr tended to be higher (17+/-8 vs 31+/-8 mm Hg; p=0.08) in ASD;
      however, left ventricular SV was not different (64+/-23 vs 58+/-23 mL; p>0.05),
      compared with control subjects. Despite normal resting left ventricular function,
      ASD patients had a significant reduction in maximum oxygen uptake (VO2max)
      (22.9+/-5.4 vs 17.3+/-4.2 mL/kg/min; p=0.005). RVSPex was higher (19+/-8 vs 51+/
      10 mm Hg; p=0.001) and the mean RVSP-VO2 slope (1+/-2 vs 18+/-3 mm Hg/L/min;
      p=0.003) and intercept (17+/-4 vs 27+/-4 mm Hg; p=0.05) were higher in the ASD
      group. VO2max correlated inversely with both RVSPr (r=-0.69; p=0.007) and RVSPex
      (r=-0.67; p=0.01). CONCLUSION: These findings suggest that adults with ASD have
      reduced exercise performance, which may be associated with an abnormal increase
      in pulmonary artery pressure during exercise.

PMID- 9631779
TI  - A comparison between systolic aortic root pressure and finger blood pressure.
AB  - BACKGROUND: Digital photoplethysmography is used to assess hemodynamic
      variability and baroreflex sensitivity. Numerous studies have critically
      evaluated the accuracy of the photoplethysmographic device against peripheral
      pressure. The aim of our study was to compare finger blood and aortic root
      pressure. METHODS: We prospectively compared simultaneous recordings of systolic
      pressure at the aortic root and finger level over three consecutive respiratory
      cycles in 15 patients (56+/-11 years) undergoing routine cardiac catheterization.
      Data were obtained at baseline, during deep breathing maneuver (0.1 Hz), and
      after left ventricular cineangiography. RESULTS: At baseline, systolic finger
      pressure overestimated systolic aortic pressure (145.2+/-22.5 vs 115.0+/-20.1 mm
      Hg; p<0.001). The pressure difference (30.2+/-17.0 mm Hg) was not influenced by
      systolic aortic pressure. There was no relationship between pressure difference
      and the main determinants of the pulse wave amplification phenomenon. There was a
      beat-to-beat relationship between finger and aortic pressure in 14 of 15 subjects
      (slope ranging from 0.37 to 1.70; ordinate: from -56 to +98 mm Hg). During the
      deep breathing maneuver and after left ventricular cineangiography, finger
      pressure still overestimated aortic pressure by 32.3+/-15.0 mm Hg and 38.3 13.9
      mm Hg, respectively (each p<0.001). There was a beat-to-beat relationship between
      systolic aortic root pressure (IAoBP) and systolic finger (FBP) in 13 of 15
      patients, with major scattering of both slopes and ordinates. Throughout the
      study, there was no predictable relationship between the level of IAoBP and
      pressure bias. CONCLUSIONS: As expected, FBP was almost always higher than IAoBP.
      Importantly, the differences in systolic pressure did not correlate with known
      determinants of the pulse wave amplification phenomenon. The device must be used
      cautiously if one wants to noninvasively track spontaneous or induced changes in
      IAoBP.

PMID- 9631780
TI  - Quantification of traumatic hemomediastinum using transesophageal
      echocardiography: impact on patient management.
AB  - STUDY OBJECTIVES: To determine whether the quantitative evaluation of
      hemomediastinum using transesophageal echocardiography (TEE) is predictive of the
      presence of a traumatic disruption of the thoracic aorta (TDA) or its branches in
      patients who have sustained severe blunt chest trauma. DESIGN: Retrospective
      study. SETTING: ICU of a tertiary referral teaching hospital. PATIENTS: Forty-one
      patients sustaining severe blunt chest trauma (32 men, nine women; mean age, 43+/
      16 years; mean Injury Severity Score, 39+/-22) who underwent a TEE study were
      divided into two groups, patients with (group TDA+, n=15) or without (group TDA-,
      n=26) major vascular injury diagnosed using an alternative method such as
      aortography, surgery, or necropsy. The control group included 41 age- and sex
      matched patients with an unremarkable TEE study performed to rule out an
      intracardiac source of emboli. INTERVENTIONS: The presence of hemomediastinum was
      quantitatively assessed by measuring the distances between the esophageal scope
      and anteromedial aortic wall (distance 1), and between the posterolateral aortic
      wall and left visceral pleura (distance 2) at the level of the aortic isthmus. An
      observer who was unaware of both medical history and final diagnosis measured the
      distances. MEASUREMENTS AND RESULTS: In group TDA+, TEE demonstrated aortic
      injuries in 13 patients, revealed an isolated hemomediastinum in one patient
      (ruptured intercostal arteries), and was unremarkable in the remaining patient,
      who sustained a disrupted right subclavian artery. No associated major vessel
      injuries were diagnosed in the group TDA- (normal aortograms). When compared to
      the control group, mean distances were greater in patients with chest trauma
      (distance 1=5.5+/-4.4 mm vs 2.7+/-0.8 mm, p=0.001; distance 2=3.8+/-5.0 mm vs
      1.2+/-0.3 mm, p=0.02). The corresponding distances were even greater in group
      TDA+ when compared with group TDA- (distance 1=8.6+/-5.9 mm vs 3.7+/-1.5 mm, and
      distance 2=7.1+/-7.0 mm vs 2.0+/-1.7; for both differences, p<0.01). A threshold
      value of 5.5 mm for distance 1 or 6.6 mm for distance 2 had a sensitivity of 80%,
      a specificity of 92%, a positive and negative predictive value of 86% and 89%,
      respectively, for the diagnosis of underlying major vascular injury. CONCLUSIONS:
      TEE allows quantitative assessment of traumatic hemomediastinum. The presence of
      a large hemomediastinum requires further evaluation by aortography, even if the
      thoracic aorta appears normal during the TEE examination, in order to rule out an
      underlying major vascular injury which may be outside the field of view of the
      echocardiographer.

PMID- 9631781
TI  - Early extubation following coronary artery bypass surgery: a prospective
      randomized controlled trial. The Fast Track Cardiac Care Team.
AB  - STUDY OBJECTIVES: To determine the safety of early extubation (EE) after coronary
      artery surgery. DESIGN: Prospective randomized controlled trial. SETTING: The
      cardiac surgery operating room and ICU of a university-affiliated teaching
      hospital. PATIENTS: One hundred eligible patients presenting for elective
      coronary artery surgery. INTERVENTIONS: Patients randomized to the EE group were
      administered a reduced dose of fentanyl (15 microg/kg) and an anesthetic
      compatible with EE, while patients randomized to the conventional extubation (CE)
      group were given fentanyl (50 microg/kg). MEASUREMENTS AND RESULTS: The time to
      extubation in the EE group (median, 240 min; range, 30 to 930 min) was
      significantly less than the CE group (median, 420 min; range, 125 to 1,140 min)
      (p<0.01). Twenty patients were withdrawn from the study according to protocol
      guidelines. There were no cases of reintubation or complications attributable to
      EE. CONCLUSIONS: By using an appropriate anesthetic technique and postoperative
      management, EE can be achieved following coronary artery bypass surgery without
      major complications.

PMID- 9631782
TI  - Atrial fibrillation after bypass surgery: does the arrhythmia or the
      characteristics of the patients prolong hospital stay?
AB  - STUDY OBJECTIVES: The goal of this study was to determine whether prolonged
      hospital stay associated with atrial fibrillation or flutter (AF) after coronary
      artery bypass graft (CABG) surgery is attributable to the characteristics of
      patients who develop this arrhythmia or to the rhythm disturbance itself. DESIGN:
      An investigation was conducted through a prospective case series. SETTING:
      Patients were from a single urban teaching hospital. PARTICIPANTS: Consecutive
      patients undergoing isolated CABG surgery between December 1994 and May 1996 were
      included in the study. INTERVENTIONS: No interventions were involved. RESULTS: Of
      436 patients undergoing isolated CABG surgery, 101 (23%) developed AF. AF
      patients were older and more likely to have obstructive lung disease than
      patients without AF, but both patients with and without AF had similar left
      ventricular function and extent of coronary disease. ICU and hospital stays were
      longer in patients with AF. Multivariate analysis, adjusted for age, gender, and
      race, demonstrated that postoperative hospital stay was 9.2+/-5.3 days in
      patients with AF and 6.4+/-5.3 days in patients without AF (p<0.001).
      CONCLUSIONS: Although AF is strongly associated with advanced age, most of the
      prolonged hospital stay appears to be attributable to the rhythm itself and not
      to patient characteristics.

PMID- 9631783
TI  - Presentation and surgical management of bronchogenic and esophageal duplication
      cysts in adults.
AB  - OBJECTIVE: Bronchogenic and esophageal duplication cysts are congenital anomalies
      of the tracheobronchial tree and foregut that are often asymptomatic at initial
      presentation in adults. Surgery is always recommended, even for patients with
      asymptomatic disease, because of the possible development of symptoms and
      complications during the natural course of the disease and because definitive
      diagnosis can be established only on surgical specimen. METHODS: Twenty-seven
      patients with bronchogenic and esophageal duplication cysts were treated in our
      institution over the last 2 decades. Ten patients (37%) were asymptomatic at
      initial presentation. Chest pain and dysphagia were the most common complaints in
      symptomatic patients affected by bronchogenic and duplication cysts,
      respectively. RESULTS: A complete excision of the cyst was performed in 26 cases,
      whereas one patient with intrapulmonary cyst underwent a right upper pulmonary
      lobectomy. A posterolateral thoracotomy was performed in 23 patients, and a video
      assisted thoracoscopy using a three-port technique was performed in the last 4
      patients. No postoperative morbidity was recorded. All patients, except one, were
      asymptomatic at a median follow-up time of 4 years. CONCLUSIONS: Surgery is the
      treatment of choice for bronchogenic and esophageal duplication cysts. Video
      assisted thoracoscopy should represent the first-line approach in these patients.

PMID- 9631784
TI  - Serial lung function and elastic recoil 2 years after lung volume reduction
      surgery for emphysema.
AB  - STUDY OBJECTIVE: To evaluate serial lung function studies, including elastic
      recoil, in patients with severe emphysema who undergo lung volume reduction
      surgery (LVRS). To determine mechanism(s) responsible for changes in airflow
      limitation. METHODS: We studied 12 (10 male) patients aged 68+/-9 years (mean+/
      SD) 6 to 12 months prior to and at 6-month intervals for 2 years after
      thoracoscopic bilateral LVRS for emphysema. RESULTS: At 2 years post-LVRS, relief
      of dyspnea remained improved in 10 of 12 patients, and partial or full-time
      oxygen dependency was eliminated in 2 of 7 patients. There was significant
      reduction in total lung capacity (TLC) compared with pre-LVRS baseline, 7.8+/-0.6
      L (mean+/-SEM) (133+/-5% predicted) vs 8.6+/-0.6 L (144+/-5% predicted)
      (p=0.003); functional residual capacity, 5.6+/-0.5 L (157+/-9% predicted) vs
      6.7+/-0.5 L (185+/-10% predicted) (p=0.001); and residual volume, 4.9+/-0.5 L
      (210+/-16% predicted) vs 6.0+/-0.5 L (260+/-13% predicted) (p=0.000). Increases
      were noted in FEV1, 0.88+/-0.08 L (37+/-6% predicted) vs 0.72+/-0.05 L (29+/-3%
      predicted) (p=0.02); diffusing capacity, 8.5+/-1.0 mL/min/mm Hg (43+/-3%
      predicted) vs 4.2+/-0.7 mL/min/mm Hg (18+/-3% predicted) (p=0.001); static lung
      elastic recoil pressure at TLC (Pstat), 13.7+/-0.5 cm H2O vs 11.3+/-0.6 cm H2O
      (p=0.008); and maximum oxygen consumption, 8.7+/-0.8 mL/min/kg vs 6.9+/-1.5
      mL/min/kg (p=0.03). Increase in FEV1 correlated with the increase in TLC
      Pstat/TLC (r=0.75, p=0.03), but not with any baseline parameter. CONCLUSION: Two
      years post-LVRS, there is variable clinical and physiologic improvement that does
      not correlate with any baseline parameter. Increased lung elastic recoil appears
      to be the primary mechanism for improved airflow limitation.

PMID- 9631785
TI  - Prolonged air leak following radical upper lobectomy: an analysis of incidence
      and possible risk factors.
AB  - STUDY OBJECTIVES: To examine the incidence and clinical significance of prolonged
      air leak (PAL) in patients undergoing radical upper lobectomy and to determine
      potential risk factors for PAL in this group of patients. DESIGN: Retrospective
      review of a prospective database. SETTING: Experience of one thoracic surgeon at
      a tertiary care cancer center. PATIENTS: One hundred consecutive patients
      undergoing right upper lobectomy and mediastinal lymph node dissection for non
      small cell lung cancer over an 11-year period. MEASUREMENTS: PAL was defined as
      an air leak lasting >7 days. Preoperative, intraoperative, and postoperative
      clinical data were collected and analyzed to determine the factors associated
      with PAL. RESULTS: PAL was the most prevalent postoperative complication,
      comprising 25.5% of all complications seen, and lasting an average of 12.1+/-5.3
      days. In 21 of the 26 patients with PAL, this complication was the only morbidity
      identified. There was no statistically significant difference in patient age,
      gender, preoperative FEV1 and diffusion of carbon monoxide, exposure to
      neoadjuvant chemotherapy, status of pulmonary fissures, or pathologic stage
      between the PAL group vs the remaining 74 patients without this complication. A
      significantly greater proportion of patients with PAL had FEV1/FVC ratio < or
      =50% (6/26 vs 5/74; p=0.02). Patients with PAL had significantly longer median
      length of hospital stay (11 vs 7 days; p=0.0001). Moreover, PAL was the single
      most common reason for an extended length of hospitalization (21/58, 36% of all
      causes). CONCLUSION: PAL is an alarmingly common postoperative complication and
      is the most frequent cause of an extended length of hospital stay in patients
      undergoing radical upper lobectomy. Severe obstructive pulmonary disease
      predisposes patients to the development of this complication.

PMID- 9631786
TI  - Recovery and limitation of exercise capacity after lung resection for lung
      cancer.
AB  - OBJECTIVE: To assess the effects of pulmonary resection for lung cancer on
      postoperative recovery and limitation of exercise capacity. METHODS: Eighty-two
      patients (20 pneumonectomies, 62 lobectomies) underwent spirometric pulmonary
      tests and exercise capacity tests preoperatively, and at 3 months and more than 6
      months after the operation. RESULTS: In the lobectomy group, FEV1 vital capacity
      (VC), and maximum oxygen consumption (VO2max) decreased significantly 3 months
      after the operation and improved after more than 6 months, but did not reach the
      preoperative values. In the pneumonectomy group, FEV1 VC, and VO2max decreased 3
      months after the surgery and the values did not recover thereafter. In comparison
      with preoperative values, the functional percentage losses after more than 6
      months for lobectomies and pneumonectomies were 11.2% and 36.1% for FEV1, 11.6%
      and 40.1% for VC, and 13.3% and 28.1% for VO2max, respectively. Postoperatively,
      maximal minute ventilation (VEmax), the maximal heart rate percentage, and
      maximal O2 pulse during the exercise test significantly decreased in both the
      lobectomy and pneumonectomy groups. Nevertheless, VEmax and O2 pulse improved
      more than 6 months after lobectomy compared with the value at 3 months, but not
      after pneumonectomy. Breathing reserve did not differ before and after surgery in
      the lobectomy group, although it decreased significantly after surgery in the
      pneumonectomy group. Subjectively, postoperative exercise after lobectomy was
      limited by leg discomfort (64% at more than 6 months after surgery); after
      pneumonectomy, exercise was limited by dyspnea (60%). CONCLUSIONS: These results
      suggest that there are differences between lobectomy and pneumonectomy for lung
      cancer in terms of recovery and limitation of exercise capacity.

PMID- 9631787
TI  - Progression of asbestosis predicts lung cancer.
AB  - STUDY OBJECTIVES: To explore whether the progression of asbestosis correlates
      with the risk of lung cancer among patients with asbestosis. DESIGN: A group of
      85 asbestosis patients (78 men and 7 women) were radiographically followed up
      between 1979 and 1987. Two or three posteroanterior radiographs taken from each
      patient in 1978 to 1979, 1983 to 1984, and 1986 to 1987 were classified according
      to the International Labour Office 1980 classification and were used to divide
      the patients into progressors and nonprogressors. Follow-up for cancer was done
      automatically through the files of the Finnish Cancer Registry from the time of
      determination of the progression status to December 31, 1994. Predictors of lung
      cancer risk were studied with a logistic regression model, and the standardized
      incidence ratio (SIR) was calculated for lung cancer. RESULTS: Of the 24 male
      patients with progressive small opacity profusion, 11 (46%) developed lung
      cancer, as opposed to 5 (9%) of the 54 male patients without progression. The SIR
      for lung cancer was 37 (95% confidence interval, 18 to 66) for the progressors
      and 4.3 (1.4 to 9.9) for the nonprogressors. In both groups, all the lung cancer
      cases occurred among smokers or ex-smokers. None of the seven female patients
      showed progressive small opacity profusion. One of them developed lung cancer. In
      the logistic regression model including all 85 asbestosis patients, radiographic
      progression of small opacity profusion (p=0.0009) and current smoking (0.0021)
      were significant predictors of lung cancer morbidity. CONCLUSIONS: Asbestosis
      patients with radiographic progression of small opacity profusion over a few
      years are at a higher risk of lung cancer than those with a less aggressive
      course of the disease. The progression of pulmonary fibrosis may be an
      independent risk factor that, in addition to smoking history and the intensity of
      asbestos exposure, could be used to estimate lung cancer risk.

PMID- 9631788
TI  - Additional information from percutaneous cutting needle biopsy following fine
      needle aspiration in the diagnosis of chest lesions.
AB  - OBJECTIVE: To determine the contribution of percutaneous cutting needle biopsy
      (PNB) subsequent to fine-needle aspiration (FNA) in the diagnosis of chest
      lesions. DESIGN: A retrospective review of 220 patients who underwent CT-guided
      FNA followed immediately by PNB performed at our center between 1988 and 1995 was
      undertaken. Thirty-eight patients were excluded because FNA and/or PNB specimens
      were nondiagnostic, yielding a study group of 182 patients. RESULTS: A diagnosis
      of malignancy was made in 141 (77.5%) and nonmalignancy in 41 (22.5%) cases. The
      yield of histospecific diagnosis due to FNA was marginally higher than PNB in
      malignant lesions (86.5% vs 78%, respectively). In contrast, PNB was superior to
      FNA for the histospecific diagnosis of benign lesions (87.8% for PNB vs 31.7% for
      FNA, p<0.00001) and lymphomas (88% for PNB vs 56% for FNA, p<0.05). In 58.8% of
      the patients with benign lesions and in 37.5% of the patients with lymphoma, PNB
      performances altered clinical management, either by avoiding further surgery or
      allowing specific medical treatment. Pneumothorax occurred in 24.7% of the cases
      but only five patients (2.7%) required hospitalization. CONCLUSION: PNB is
      extremely effective for making a specific diagnosis in benign lesions compared
      with FNA. PNB does not increase the yield of histospecific diagnosis for
      malignant lesions except for the subset of lymphoma, where it seems to provide
      important additional information in many instances. We recommend that FNA be
      performed as the initial procedure, followed by PNB in cases of equivocal
      diagnosis of carcinoma, for lymphoma and for suspected benign lesions.

PMID- 9631789
TI  - Detection of occult micrometastases in non-small cell lung carcinoma by reverse
      transcriptase-polymerase chain reaction.
AB  - BACKGROUND: The 5-year survival rate following surgical resection of Stage I or
      Stage II non-small cell lung carcinoma (NSCLC) is 30% to 50%, probably because of
      undetected occult micrometastases (OMs) at the time of surgery. Other
      investigators have detected OMs in bone marrow and histologically negative lymph
      nodes from patients with NSCLC using immunohistochemical staining to cytokeratins
      and cell surface glycoproteins. STUDY OBJECTIVE: To develop and evaluate an assay
      based on the reverse transcriptase-polymerase chain reaction (RT-PCR) for the
      detection of OMs in NSCLC. PATIENTS: Twenty-eight patients with benign or
      malignant thoracic pathology. Samples of primary tumors and lymph nodes were
      collected at the time of surgical resection or mediastinoscopic lymph-node
      biopsy. RESULTS: Using RT-PCR to detect messenger RNA (mRNA) transcripts for MUC1
      (a cell surface glycoprotein present in lung tissue but absent from normal lymph
      nodes), OMs were identified in 33 of 88 lymph nodes determined to be free of
      tumor by hematoxylin and eosin staining. Eleven of 11 control mediastinal lymph
      nodes from patients without malignancy failed to express detectable MUC1
      transcripts. Dilutional experiments demonstrate that the assay can detect one
      MUC1-positive NSCLC cell in 1x10(7) MUC1-negative cells. A comparison of our RT
      PCR assay to immunohistochemistry specific for the MUC1 glycoprotein suggests
      that RT-PCR may be more sensitive than immunohistochemistry for the detection of
      NSCLC OMs. CONCLUSIONS: This study demonstrates that RT-PCR for MUC1 mRNA can
      detect the presence of MUC1 mRNA in histologically negative lymph nodes from
      patients with NSCLC. The prognostic significance of these findings is currently
      unknown.

PMID- 9631790
TI  - Prediction of mortality in febrile medical patients: How useful are systemic
      inflammatory response syndrome and sepsis criteria?
AB  - STUDY OBJECTIVES: The aim was to evaluate demographic, clinical, and laboratory
      variables in febrile patients, with or without a microbiologically confirmed
      infection, for prediction of death, in comparison to the systemic inflammatory
      response syndrome (SIRS) and its criteria, such as abnormal temperature,
      tachycardia, tachypnea, and abnormal WBC count, and to sepsis, that includes SIRS
      and an infection. DESIGN: A prospective cohort study. SETTING: Department of
      internal medicine at a university hospital. PATIENTS: In 300 consecutive,
      hospitalized medical patients with new onset of fever, demographic, clinical, and
      laboratory variables were obtained during the 2 days after inclusion, while
      microbiological results for a follow-up period of 7 days were collected. Patients
      were followed up for survival or death, up to a maximum of 28 days after
      inclusion. MEASUREMENTS AND RESULTS: Of all patients, 95% had SIRS, 44% had
      sepsis with a microbiologically confirmed infection, and 9% died. A model with a
      set of variables all significantly (p<0.01) contributing to the prediction of
      mortality was derived. The set included the presence of hospital-acquired fever,
      the peak respiratory rate, the nadir score on the Glasgow coma scale, and the
      nadir albumin plasma level within the first 2 days after inclusion. This set of
      variables predicted mortality for febrile patients with microbiologically
      confirmed infection even better. The predictive values for mortality of SIRS and
      sepsis were less than that of our set of variables. CONCLUSIONS: In comparison to
      SIRS and sepsis, the new set of variables predicted mortality better for all
      patients with fever and also for those with microbiologically confirmed infection
      only. This type of effort may help in refining definitions of SIRS and sepsis,
      based on prognostically important demographic, clinical, and laboratory variables
      that are easily obtainable at the bedside.

PMID- 9631791
TI  - Infective exacerbations of chronic bronchitis: relation between bacteriologic
      etiology and lung function.
AB  - STUDY OBJECTIVE: In patients with severe COPD, acute infective exacerbations are
      frequent. Streptococcus pneumoniae and Haemophilus influenzae are the most
      commonly isolated bacteria in sputum cultures from these patients. We
      hypothesized that in patients with advanced disease, Gram-negative bacteria other
      than H influenzae play at least an equally important role. METHODS: We evaluated
      clinical data and sputum culture results from 211 unselected COPD patients
      admitted to our hospital with an acute infective exacerbation of COPD. One
      hundred twelve patients fulfilled our protocol criteria of reliable microbiologic
      results and reproducible lung function tests; the patients were categorized
      according to the recently published three stages of severity. RESULTS: Lung
      function tests revealed an FEV1 of > or =50% of the predicted value in 30
      patients (stage I), an FEV1 of 35% to <50% of the predicted value in 30 patients
      (stage II), and an FEV1 of < or =35% of the predicted value in 34 patients (stage
      III). Bacteria were classified into three groups: group 1 contained S pneumoniae
      and other Gram-positive cocci; group 2, H influenzae and Moraxella catarrhalis;
      and group 3, Enterobacteriaceae and Pseudomonas spp. For all patients together,
      the most frequently isolated bacteria were group 3 organisms (Enterobacteriaceae
      and Pseudomonas spp, 48.2%), followed by group 1 organisms (S pneumoniae and
      other Gram-positive cocci, 30.4%), and group 2 organisms (H influenzae and M
      catarrhalis, 21.4%). In stage I patients, 14 of 30 had bacteria from group 1,
      seven of 30 had group 2, and nine of 30 had group 3. In stage II patients, eight
      of 30 had group 1 bacteria, 10 of 30 had group 2, and 12 of 30 had group 3. In
      stage III patients, 12 of 52 had group 1 bacteria, seven of 52 had group 2, and
      22 of 52 had group 3. The three groups of bacteria causing infective
      exacerbations were unevenly distributed among the three severity stages of lung
      function (p=0.016). CONCLUSION: There is a correlation between deterioration of
      lung function and the bacteria isolated from patients with infective
      exacerbations of COPD. In acute infective exacerbations, Enterobacteriaceae and
      Pseudomonas spp are the predominant bacteria in patients with an FEV1 < or =35%
      of the predicted value.

PMID- 9631792
TI  - Suspected respiratory tract infection in the tracheostomized child: the pediatric
      pulmonologist's approach.
AB  - STUDY OBJECTIVES: It is difficult to determine, in the child with a long-term
      tracheostomy, when bacterial airway colonization has progressed to a respiratory
      infection requiring antibiotic treatment. Our aim was to investigate whether
      there is a consensus regarding this and related chronic care issues among
      clinicians treating these patients. DESIGN AND SETTING: A questionnaire asking
      about practices regarding use of tracheal aspirate cultures and antibiotics was
      distributed to 47 pediatric pulmonary centers. PARTICIPANTS: Individuals
      representing 34 centers (72%), caring for 10 to 400 patients, responded.
      INTERVENTIONS: None. RESULTS: At 65% of centers, management is variable,
      dependent on the patient's underlying condition. The most common indications to
      obtain a culture were change in secretions (91%) or fever without an obvious
      source (21 centers). Indications to treat with antibiotics included many
      leukocytes in secretions (21 centers) or a respiratory illness (18 centers). When
      treating, 97% prescribe antibiotics empirically, most often enterally; nine
      centers use inhaled antibiotics. In most centers (79%), management is often done
      by telephone. CONCLUSIONS: Although pediatric pulmonologists tend to have similar
      approaches to assessment and management of suspected respiratory tract infections
      in tracheostomized children, no clear consensus exists, and much of current
      practice is empirical. To optimize care of these patients, studies should be
      conducted to develop criteria to objectively differentiate bacterial airway
      "colonization" from "infection."

PMID- 9631793
TI  - A comparison of induced and expectorated sputum for the diagnosis of Pneumocystis
      carinii pneumonia.
AB  - STUDY OBJECTIVES: To compare the sensitivities of expectorated and induced sputum
      for the diagnosis of Pneumocystis carinii pneumonia (PCP). DESIGN: Retrospective
      review. SETTING: Academic medical center. PATIENTS: Forty-five patients diagnosed
      as having PCP who had direct fluorescent antibody testing for P carinii on either
      expectorated or induced sputum. RESULTS: Patients were stratified according to
      the method of sputum production (induced vs expectorated). The two groups were
      similar with respect to demographic characteristics, use of prophylaxis with
      aerosolized pentamidine, serum lactate dehydrogenase level, and arterial oxygen
      level. When only the initial sputum for each patient was analyzed, there was a
      similar sensitivity of induced sputum, positive in 10 of 18 samples (56%), and
      expectorated sputum, positive in 14 of 27 samples (52%) (p>0.05). CONCLUSION:
      There was no significant difference in the sensitivity of induced and
      expectorated sputum for the diagnosis of PCP when the direct fluorescent antibody
      method of staining was used.

PMID- 9631794
TI  - Effect of cold air on exercise capacity in COPD: increase or decrease?
AB  - STUDY OBJECTIVE: To clarify the effect of cold air on exercise capacity in COPD.
      DESIGN: Cycle ergometer tests under different environmental conditions. SETTING:
      Pulmonary function laboratory and an environmental chamber at a university
      hospital. PARTICIPANTS: Eighteen patients with stable COPD; 14 completed the
      study. INTERVENTIONS: A preliminary cycle ergometer test followed by two
      incremental, symptom-limited cycle ergometer tests, one at 24 degrees C and the
      other at -20 degrees C. MEASUREMENTS: On the first study day: arterial blood gas
      analysis, 12 to 15 s maximal voluntary ventilation, maximal expiratory flow
      volume curves before and 1 h after inhalation of 80 microg of ipratropium
      bromide, and diffusion capacity of the lung. During the exercise challenges:
      spirometric indices, minute ventilation (VE), oxygen consumption (VO2), carbon
      dioxide production (VCO2), facial skin temperature, and heart rate. The feeling
      of dyspnea was assessed with a visual analogue scale. RESULTS: The maximal work
      load was 87.5+/-7.3 W at -20 degrees C compared with 96.4+/-6.9 W at 24 degrees C
      (p<0.05). Accordingly, the exercise duration was shorter in the cold. Exercise
      dyspnea was more severe in the cold at equal work loads. The shortening of
      exercise duration induced by cold air correlated with the enhancement of exercise
      dyspnea. Furthermore, cold air cooled the facial skin and induced immediate
      bronchoconstriction. VE, VO2, VCO2, and heart rate did not differ between the
      warm and cold challenges. CONCLUSIONS: Cold air decreases exercise capacity in
      COPD, probably by increasing exercise dyspnea.

PMID- 9631795
TI  - Respiratory resistance in the emergency department: a reproducible and responsive
      measure of asthma severity.
AB  - OBJECTIVES: To determine, in preschool children with an acute asthma
      exacerbation, the responsiveness to change of respiratory resistance measurements
      obtained by the forced oscillation (Rfo) technique, and to identify the magnitude
      of change indicative of airway obstruction reversibility. DESIGN/SETTING: A
      prospective observational study of 114 children, aged 3 to 17 years, untrained in
      the Rfo technique and treated for acute asthma in a tertiary-care pediatric
      emergency department (ED). MEASUREMENTS: A physical examination followed by three
      measurements of respiratory resistance by forced oscillation were obtained at 8
      Hz (Rfo8) and at 16 Hz (Rfo16). In cooperative children, routine spirometry that
      included FEV1 was also performed on the Custo Vit R (Custo Med; Munich, Germany).
      All measurements were obtained twice during the course of the ED treatment,
      before and after treatment with nebulized bronchodilators. RESULTS: The Rfo8 and
      Rfo16 measurements were highly reproducible (reproducibility coefficients >0.85).
      Both the Rfo8 and Rfo16 were at least as responsive to change (responsiveness
      coefficients of 2.3 and 1.2, respectively) as was FEV1 (2.0) and the four
      clinical signs most sensitive to change (0.6 to 1.0). A 19% change in Rfo8 was
      suggestive of significant reversibility. CONCLUSIONS: In the assessment of
      children aged > or =3 years with acute asthma exacerbation, the respiratory
      resistance measurements are highly reproducible and responsive to change,
      particularly when obtained at 8 Hz. A 19% change from baseline Rfo8 is suggestive
      of reversibility. This technique appears to be an attractive alternative in the
      evaluation of children who are too young or too sick to perform spirometry
      reproducibly.

PMID- 9631796
TI  - Regional lung deposition and clearance of 99mTc-labeled beclomethasone-DLPC
      liposomes in mild and severe asthma.
AB  - OBJECTIVE: To compare the distribution and clearance of inhaled beclomethasone
      dipropionate (Bec)-dilauroylphosphatidylcholine (DLPC) liposomes in patients with
      mild and severe asthma. DESIGN: A 99mTc-labeled Bec-DLPC suspension was delivered
      via a nebulizer (Aerotech II). Immediately after inhalation, anterior and
      posterior views of the lungs and an anterior view of the oropharynx were measured
      by a large field gamma camera with the patient in a supine position. To evaluate
      the mucociliary clearance of the inhaled liposomes, anterior and posterior lung
      scans were repeated 1, 2, 4, and 24 h after the aerosol delivery. PATIENTS: Ten
      patients with mild asthma (FEV1 >80% of the predicted) and 10 patients with
      severe asthma (FEV1 <60% of the predicted) were included in an open, parallel
      group study. RESULTS: Clearance is more rapid among patients with severe asthma
      (p<0.0001). At the 4-h measurement, a mean of 82% (SD, 5.9) of the total
      pulmonary dose was detected in the lungs of patients with mild asthma while in
      those with severe asthma the figure was 69% (SD, 10.9). The ratio between central
      and peripheral deposition was significantly higher for patients with severe
      asthma than for those having a mild form of the disease; 1.07 (SD, 0.29) and 0.76
      (SD, 0.07), respectively (p=0.008). CONCLUSIONS: Inhaled Bec-DLPC liposomes were
      deposited more centrally in the lower airways of patients with severe asthma than
      those having a milder form of the disease. The clearance of Bec-DLPC liposomes is
      strikingly slow in both groups of asthmatic patients. However, due to the more
      peripheral penetration of inhaled liposomes in patients with mild asthma, the
      clearance rate in this group was slower than in those with severe asthma.

PMID- 9631797
TI  - Relative survival analysis of 252 patients with COPD receiving long-term oxygen
      therapy.
AB  - OBJECTIVES: A survival analysis was conducted on patients with COPD receiving
      long-term oxygen therapy (LTOT) to compare two different statistical methods.
      METHODS: We used a multivariate crude (observed) survival model (Cox) and a
      multivariate relative survival model (Hakulinen). Only the latter is able to
      correct the survival by adjusting it to the normal life expectancy of the studied
      patients. PATIENTS: Two hundred fifty-two hypoxemic COPD patients (207 male)
      requiring LTOT were included. Mean PaO2 was <50 mm Hg before oxygen therapy. Mean
      age was >69 years (SE: 9.9). They had severe bronchial obstruction: mean FEV1 was
      <33% (10.6) of predicted values, with some CO2 retention: mean PaCO2 was 45.6
      (7.1) mm Hg. By December 31, 1995, 189 patients had died (75%) and 13 (5%) were
      unavailable for follow-up. RESULTS: The overall crude survival was poor: 80.9%
      after 1 year, 67.1% after 2 years, 34.7% after 5 years, and 7.1% after 10 years.
      In the crude multivariate analysis (Cox), the negative prognostic factors were
      age and hypercapnia. The overall relative survival (Hakulinen), corrected for
      life expectancy, was 82.8% after 1 year, 70.8% after 2 years, 41.5% after 5
      years, and 10.25% after 10 years. In the final multivariate relative model, age
      was no longer significant and the only bad prognostic factor was hypercapnia with
      a relative risk of 1.97 (1.16 to 3.34). CONCLUSION: This work shows the
      inadequacy of the Cox observed survival model when it comes to appreciating the
      real prognostic impact of age, because of the confusing factor associated with a
      normal life expectancy.

PMID- 9631798
TI  - Effect of regular use of high-dose nebulized beta2-agonists on resting energy
      expenditure, weight, and handgrip strength in patients with chronic airflow
      limitation.
AB  - STUDY OBJECTIVES: A proportion of patients with chronic airflow limitation (CAL)
      have a raised resting energy expenditure (REE). The mechanism underlying this is
      not known. The question of whether the increased REE seen in some patients with
      CAL is due to beta2-agonist therapy has arisen, and the aim of this study was to
      examine REE, body composition, and peripheral muscle strength in patients before
      and after the use of regular high-dose beta2-agonists administered by nebulizer.
      DESIGN: Prospective observational study. SETTING: Respiratory outpatient clinic.
      PARTICIPANTS: Twenty outpatients with CAL being considered for a home nebulizer
      prescription. INTERVENTIONS: REE was measured by indirect calorimetry. Fat-free
      mass and handgrip strength were measured. Quality of life was assessed by the St.
      George's Hospital Respiratory Questionnaire. All subjects were assessed
      independently of this study for provision of a home nebulizer using a standard
      protocol. Based on the assessment, either standard-dose salbutamol therapy was
      continued or a nebulizer was provided with a prescription for high-dose
      salbutamol (5 mg qd). A mean of 8.1 months later (range, 3 to 16 months), 16
      patients were restudied. MEASUREMENTS AND RESULTS: Eight patients had been taking
      regular high-dose nebulized salbutamol, and eight had continued taking standard
      dose salbutamol by metered dose inhaler. There was no difference in baseline
      measures between the group who were later prescribed high-dose salbutamol and the
      group who were not. There were no changes in REE, anthropometric measures, or
      handgrip strength over time in either of the groups. CONCLUSIONS: The long-term
      use of high-dose nebulized beta2-agonists in patients with chronic airflow
      limitation has no effect on baseline REE, handgrip strength, weight, or body
      composition.

PMID- 9631799
TI  - Upper airway changes in snorers and mild sleep apnea sufferers after
      uvulopalatopharyngoplasty (UPPP).
AB  - OBJECTIVES: We used upper airway (UA) imaging in 20 patients to determine (1)
      whether an effective enlargement of the UA is obtained after
      uvulopalatopharyngoplasty (UPPP), and (2) whether UA modifications explain the
      results of such surgery. METHODS: Cephalometric measurements were made to assess
      the posterior airway space, the length and width of the soft palate, and the
      distance between the hyoid bone and the mandibular plane. Pharyngeal CT measured
      the airway cross-sectional area (CSA) at each 10-mm slice from 10 mm above (-10)
      to 40 mm below (+40) the hard palate. Polysomnography was performed before and
      after surgery (10+/-10 [SD] months). Good responders were defined by an apnea
      hypopnea index (AHI) of <10 postsurgery or, in patients in whom AHI was initially
      <10, a reduction of AHI >50% of the initial AHI. RESULTS: Twenty patients
      (age=45+/-11 years) were studied. For the whole group, the mean body mass index
      (26+/-4 kg/m2) and AHI (14+/-13 vs 18+/-16/h) were unchanged after UPPP. The
      results of the surgery were mediocre with 7 good responders (35%) and 13
      nonresponders (65%) defined by polysomnographic criteria. The only changes on UA
      imaging for the group as a whole after UPPP were decrease in length (40+/-6 vs
      29+/-5 mm, p< or =0.0006) and increase in width of the soft palate (11.5+/-2.7 vs
      13.6+/-3.5 mm, p< or =0.006). The increase or decrease in minimal CSA at the
      oropharyngeal (OP) level after UPPP was significantly correlated with the change
      in AHI (r=-0.54, p<0.02). Moreover, the changes in CSA obtained at the OP level
      were significant only in the patients who responded favorably to UPPP (7 vs 13
      nonresponders). CONCLUSIONS: Postoperative OP enlargement is associated with a
      good outcome of UPPP. Persistent narrowing in nonresponders could be due to the
      increase in soft palate width after surgery.

PMID- 9631800
TI  - Changes in urinary uric acid excretion in obstructive sleep apnea before and
      after therapy with nasal continuous positive airway pressure.
AB  - STUDY OBJECTIVE: To assess the utility of urinary uric acid excretion as a marker
      of nocturnal hypoxia in patients with obstructive sleep apnea-hypopnea syndrome
      (OSAHS) before and after the institution of nasal continuous positive airway
      pressure (CPAP). DESIGN: Prospective, open. SETTING: Sleep Disorders Laboratory,
      Veterans Affairs Medical Center. PARTICIPANTS: Thirty consecutive male subjects,
      20 with OSAHS and 10 without OSAHS. MEASUREMENTS AND METHODS: Spot morning urine
      and venous blood samples were obtained in all subjects; samples were also
      obtained after the application of CPAP in those with OSAHS. Uric acid excretion,
      normalized to creatinine clearance, was calculated as the product of urinary uric
      acid and serum creatinine concentrations divided by urine creatinine
      concentration. In patients with OSAHS, uric acid excretion was 0.55+/-0.1 mg/dL
      before CPAP therapy and decreased to 0.30+/-0.01 mg/dL after CPAP therapy (p <
      0.001). The latter value did not differ significantly from the mean value (0.32+/
      0.03 mg/dL) in the control group. Uric acid excretion in OSAHS patients
      correlated significantly with the apnea-hypopnea index (r=0.42; p<0.0003).
      CONCLUSION: Uric acid excretion is increased in OSAHS patients and normalizes
      after CPAP treatment, most likely reflecting differences in tissue oxygenation
      between the two conditions. Further studies in large number of patients may
      confirm the usefulness of this simple test for diagnosis and follow-up of
      patients with OSAHS.

PMID- 9631801
TI  - Isolated pulmonary capillaritis and diffuse alveolar hemorrhage in rheumatoid
      arthritis and mixed connective tissue disease.
AB  - STUDY OBJECTIVES: To demonstrate that pulmonary capillaritis and diffuse alveolar
      hemorrhage (DAH) occur and are isolated to the lung and therefore not part of
      systemic vasculitis at the time of the DAH episode in rheumatoid arthritis (RA)
      and mixed connective tissue disease (MCTD). DESIGN: Lung biopsy specimens from
      patients with DAH were reviewed and those with the histologic features of
      pulmonary capillaritis were identified. SETTING: The patients were selected from
      seven Denver-area general hospitals. PATIENTS: Fifty-eight patients with biopsy
      specimen proved pulmonary capillaritis (1991 to 1997) were identified and
      classified according to disease. Three patients met the American Rheumatism
      Association criteria for RA and one patient fulfilled clinical and serologic
      criteria for MCTD. INTERVENTIONS: All clinical, laboratory, and radiographic data
      on initial presentation and at follow-up periods were extracted from the charts
      of the four study patients. Histologic slides were reviewed and immunofluorescent
      studies of lung tissue were performed. MEASUREMENTS AND RESULTS: All four
      patients had a connective tissue disease diagnosis prior to the DAH episode.
      Symptoms referable to pulmonary capillaritis were of short duration (2 to 14
      days) and there was no clinical or serologic evidence for an accompanying
      systemic vasculitis, in particular glomeronephritis. Three patients, two with RA
      and one with MCTD, demonstrated pulmonary immune complex deposition. Three
      resolved their illness following IV methylprednisilone and cyclophosphamide
      therapy. One RA patient died following a myocardial infarction. In the three
      survivors, no further episodes of DAH have occurred after a mean of 24 months
      (range, 10 to 48 months). CONCLUSIONS: To our knowledge, these are the first
      cases of DAH due to pulmonary capillaritis documented to complicate RA and MCTD.
      The capillaritis was not part of a systemic vasculitis at the time of the DAH
      episode, but rather represented an isolated small-vessel vasculitis of the lungs
      in this group of patients. Immune complex deposition may be involved in the
      pathogenesis.

PMID- 9631802
TI  - Does N-acetyl-L-cysteine influence cytokine response during early human septic
      shock?
AB  - STUDY OBJECTIVE: To assess the effects of adjunctive treatment with N-acetyl-L
      cysteine (NAC) on hemodynamics, oxygen transport variables, and plasma levels of
      cytokines in patients with septic shock. DESIGN: Prospective, randomized, double
      blind, placebo-controlled study. SETTING: A 24-bed medicosurgical ICU in a
      university hospital. PATIENTS: Twenty-two patients included within 4 h of
      diagnosis of septic shock. INTERVENTIONS: Patients were randomly allocated to
      receive either NAC (150 mg/kg bolus, followed by a continuous infusion of 50
      mg/kg over 4 h; n= 12) or placebo (n=10) in addition to standard therapy.
      MEASUREMENTS: Plasma concentrations of tumor necrosis factor-alpha (TNF),
      interleukin (IL)-6, IL-8, IL-10, and soluble tumor necrosis factor-alpha receptor
      p55 (sTNFR-p55) were measured by sensitive immunoassays at 0, 2, 4, 6 and 24 h.
      Pulmonary artery catheter-derived hemodynamics, blood gases, hemoglobin, and
      arterial lactate were measured at baseline, after infusion (4 h), and at 24 h.
      RESULTS: NAC improved oxygenation (PaO2/FIO2 ratio, 214+/-97 vs 123+/-86; p<0.05)
      and static lung compliance (44+/-11 vs 31+/-6 L/cm H2O; p<0.05) at 24 h. NAC had
      no significant effects on plasma TNF, IL-6, or IL-10 levels, but acutely
      decreased IL-8 and sTNFR-p55 levels. The administration of NAC had no significant
      effect on systemic and pulmonary hemodynamics, oxygen delivery, and oxygen
      consumption. Mortality was similar in both groups (control, 40%; NAC, 42%) but
      survivors who received NAC had shorter ventilator requirement (7+/-2 days vs 20+/
      7 days; p<0.05) and were discharged earlier from the ICU (13+/-2 days vs 32+/-9
      days; p<0.05). CONCLUSION: In this small cohort of patients with early septic
      shock, short-term IV infusion of NAC was well-tolerated, improved respiratory
      function, and shortened ICU stay in survivors. The attenuated production of IL-8,
      a potential mediator of septic lung injury, may have contributed to the lung
      protective effects of NAC.

PMID- 9631803
TI  - The compensatory anti-inflammatory cytokine interleukin 10 response in pediatric
      sepsis-induced multiple organ failure.
AB  - STUDY OBJECTIVES: To determine the circulating anti-inflammatory cytokine
      interleukin 10 (IL-10) response during the development of sepsis-induced multiple
      organ failure in children. DESIGN: Prospective study. SETTING: University
      pediatric ICU. PATIENTS: Fifty-three consecutive children with sepsis and 15
      critically ill children without sepsis. INTERVENTIONS: Plasma IL-10, interleukin
      6 (IL-6), and nitrite+nitrate (stable end products of nitric oxide) levels and an
      organ failure index (OFI indicating the number of failing organ systems) were
      determined in 53 children on days 1 to 3 of sepsis and in control children on day
      1. The effect of exogenous human IL-10 or neutralizing IL-10 antibody on
      supernatant IL-6 levels in ex vivo whole blood culture from 17 children on day 1
      of sepsis. MEASUREMENTS AND RESULTS: Children with three or more organ failures
      had higher plasma IL-10 levels than children with less than 3 organ failures
      (days 1 and 3; p<0.05). Children who developed sequential pulmonary/hepatic/renal
      failure had higher IL-10 levels (days 1 to 3; p<0.05). Nonsurvivors had higher IL
      10 levels (day 3; p<0.05). IL-10 levels correlated with IL-6 levels (days 1 and
      2) and nitrite+nitrate levels (days 1 and 3; p<0.05). Whole blood samples
      incubated ex vivo with exogenous recombinant human IL-10 had decreased
      supernatant IL-6 levels (p<0.05) and neutralizing IL-10 antibody showed no
      significant effect. CONCLUSION: A persistent compensatory anti-inflammatory
      cytokine response characterizes sepsis-induced multiple organ failure.
      Administration of exogenous IL-10 may inhibit the early proinflammatory response;
      however, identification of individual immune responsiveness and possibility of
      persistent infection could be important to rational use in the later stages of
      pediatric sepsis.

PMID- 9631804
TI  - Expression of inducible nitric oxide synthase and inflammatory cytokines in
      alveolar macrophages of ARDS following sepsis.
AB  - STUDY OBJECTIVE: The objective of this study was to evaluate the role of
      inducible nitric oxide synthase (iNOS) and proinflammatory cytokines in alveolar
      macrophages (AMs) in the pathogenesis of ARDS following sepsis. SETTING: ICU in a
      university hospital. DESIGN: Prospective exploratory, open-labeled study was
      carried out. PATIENTS: A total of 24 patients were investigated: 8 patients
      diagnosed as having ARDS following sepsis (ARDS group); 8 patients under general
      anesthesia in the operating room whose lung functions were normal (control
      group); and 8 patients who were intubated and artificially ventilated for 1 week
      in the ICU whose lung functions were not deteriorated without fulfilling the ARDS
      criteria and whose general state fulfilled the sepsis criteria (long-term
      ventilation group, or LTV group). MEASUREMENTS AND RESULTS: The expression of
      iNOS, interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and interleukin-8 (IL
      8) in AMs obtained from BAL fluid (BALF) was determined by the immunofluorescent
      technique. We observed the significant expression of iNOS, IL-6, and IL-8 only in
      the ARDS group. Meanwhile, NOx (the sum of NO2- + NO3-) was elevated in the BALF
      supernatant, and IL-6 and IL-8 levels in both the BALF supernatant and the serum
      were also elevated in the ARDS group. No significant expressions were detected in
      the control and the LTV group. CONCLUSIONS: The result that iNOS was detected
      only in ARDS patients following sepsis suggests that iNOS together with
      proinflammatory cytokines produced by AMs might play a pivotal role in the
      pathogenesis of acute lung injury and be useful for monitoring disorders in the
      lung in such conditions.

PMID- 9631805
TI  - Effect of L-NAME, an inhibitor of nitric oxide synthesis, on cardiopulmonary
      function in human septic shock.
AB  - STUDY OBJECTIVES: We tested the effects of continuous infusion of N(G)-nitro-L
      arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis, on
      cardiovascular performance and pulmonary gas exchange in patients with
      hyperdynamic septic shock. DESIGN: Prospective clinical study. SETTING: ICU of a
      university hospital. PATIENTS: Eleven critically ill patients with severe
      refractory septic shock. INTERVENTIONS: Standard hemodynamic measurements were
      made and blood samples taken before, during, and after 12 h of continuous
      infusion of 1 mg/kg/h of L-NAME. MEASUREMENTS AND RESULTS: Continuous infusion of
      L-NAME increased mean arterial pressure (MAP) from 65+/-3 (SEM) to 93+/-4 mm Hg
      and systemic vascular resistance (SVR) from 962+/-121 to 1,563+/-173 dyne x s x
      cm(-5)/m2. Parallel to this, cardiac index (CI) decreased from 4.8+/-0.4 to 3.9+/
      0.4 L/min/m2 and myocardial stroke volume (SV) was reduced from 43+/-3 to 34+/-3
      mL/m2. Left ventricular stroke work was increased in the first hour of L-NAME
      infusion from 31+/-3 to 43+/-4 g x m/m2 (all p<0.01 compared with baseline).
      Heart rate, cardiac filling pressures, and right ventricular stroke work did not
      change significantly (p>0.05). L-NAME increased the ratio of arterial PO2 to the
      fraction of inspired O2 from 167+/-23 to 212+/-27 mm Hg (p<0.05). Venous
      admixture (QVA/QT) was reduced from 19.4+/-2.6% to 14.2+/-2.1% (p<0.05) and
      oxygen extraction ratio increased from 21.1+/-2.4% to 25.3+/-2.7% (p<0.05).
      Oxygen delivery (DO2) was reduced following L-NAME, whereas oxygen uptake and
      arterial lactate and pH were unchanged. CONCLUSIONS: Prolonged inhibition of NO
      synthesis with L-NAME can restore MAP and SVR in patients with severe septic
      shock. Myocardial SV and CI decrease, probably as a result of increased
      afterload, since heart rate and stroke work were not reduced. L-NAME can improve
      pulmonary gas exchange with a concomitant reduction in QVA/QT. L-NAME did not
      promote anaerobe metabolism despite a reduction in DO2.

PMID- 9631806
TI  - The value of routine posttracheostomy chest radiography.
AB  - OBJECTIVE: This study proposes to evaluate the efficacy of routine
      posttracheostomy chest radiography. DESIGN: A retrospective chart review provided
      the framework of this study. SETTING: The study took place at a university
      teaching hospital-level one trauma center. PATIENTS: The study included 293
      patients undergoing elective tracheostomy between 1989 and 1993. MEASUREMENTS AND
      RESULTS: Data extracted from the charts included indication for tracheostomy,
      immediate preoperative and postoperative chest radiograph reports, management
      changes made secondarily to radiographic findings, including chest tube
      placement, institution of chest physiotherapy, and need for tracheal tube
      reposition. Complications were defined as findings not noted on the preoperative
      radiographs; these were pneumothorax, tube malposition, atelectasis, or clinical
      information resulting in management changes. All patients received postoperative
      chest radiographs in the trauma ICU. Statistical analysis of our data was carried
      out using the chi2 test. Patients with chest tubes in place at the time of
      surgery were the only group who were excluded so as not to confuse whether
      pneumothorax developed postoperatively. Of the initial 293 patients, 25 patients
      were excluded on the basis of having a chest tube. The remaining 268 charts were
      analyzed; 220 (82%) patients underwent tracheostomy for ventilator-dependent
      respiratory failure, 31 (12%) due to multiple facial fractures, 6 (2.1%)
      secondary to penetrating neck wounds, and 11 (4%) as a result of refractory vocal
      cord edema. One (0.3%) patient was found to have a postoperative 10% apical
      pneumothorax. Eight (2.4%) patients were found to have postoperative subsegmental
      atelectasis. There were no significant (p>0.05) management changes implemented as
      a result of these findings. No new infiltrates, effusions, or malpositioned tubes
      were noted. Deletion of routine posttracheostomy radiographs would save $52.39
      per patient (cost) or $15,350 for 293 patients and $35,453 in total patient
      charges. CONCLUSIONS: Abnormalities revealed by routine chest radiography after
      tracheostomy did not appear to alter patient management frequently enough to
      warrant the costs. A randomized, prospective study should be performed to analyze
      the safety of abandoning this practice.

PMID- 9631807
TI  - Delivery of inhaled nitric oxide using the Ohmeda INOvent Delivery System.
AB  - OBJECTIVES: We evaluated the Ohmeda INOvent Nitric Oxide Delivery System, which
      uses an inspiratory flow sensor to inject a synchronized and proportional nitric
      oxide (NO) flow into the mechanical ventilator circuit. This system should
      deliver a constant NO concentration independent of ventilator mode, minute
      ventilation, fraction of inspired oxygen, or ventilator brand. It should also
      minimize nitrogen dioxide (NO2) formation. METHODS: NO delivery by the INOvent
      and a premixing NO delivery system were compared using two ventilators (Puritan
      Bennett 7200 and Servo 900C). NO concentration was measured within the trachea of
      an attached lung model using a fast-response chemiluminescence NO analyzer. NO
      concentration was also measured in the inspiratory limb using the electrochemical
      analyzer of the INOvent. For three NO concentrations (2, 5, and 20 ppm), the
      ventilators were set for constant flow volume control ventilation, pressure
      control ventilation, and spontaneous breathing with pressure support ventilation
      or synchronized intermittent mandatory ventilation. Different tidal volumes (300,
      500, 750, and 1,000 mL) and inspiratory times (1 and 2 s) were evaluated. NO2
      formation for both ventilators and delivery systems were evaluated at 20 ppm and
      95% O2-. RESULTS: Regardless of ventilatory pattern, both systems delivered a
      constant NO concentration. The error between the target and the delivered NO dose
      for the INOvent was -1.3+/-3.6% with the Puritan-Bennett 7200 and -3.9+/-4.3%
      with the Servo 900C. For the premixing system, the error was -5.5+/-4.8% with the
      Puritan-Bennett 7200 and -6.7+/-6.2% with the Servo 900C. NO2 concentrations were
      0.5+/-0.1 ppm during NO delivery by the INOvent, 5.8+/-1.6 ppm when NO was
      premixed with air, 0.3+/-0.1 ppm when NO was premixed with N2. CONCLUSION: The
      INOvent provides a constant NO concentration independent of the ventilatory
      pattern, and NO2 formation is minimal.

PMID- 9631808
TI  - The combination of partial liquid ventilation and inhaled nitric oxide in the
      severe oleic acid lung injury model.
AB  - STUDY OBJECTIVES: To elucidate the efficacy of the combination of inhaled nitric
      oxide (NO) and partial liquid ventilation (PLV) in ARDS. DESIGN: Prospective,
      randomized, controlled study. SETTING: A research laboratory at a university
      medical center. SUBJECTS: Thirty-two rabbits. INTERVENTIONS: Animals were
      anesthetized and ventilated via tracheostomy (tidal volume=40 mL; respiratory
      rate=25 breaths/min; fraction of inspired oxygen=0.99). After 0.08 mL/kg (0.071
      g/kg) oleic acid was administered via the central venous route, animals were
      randomly divided into the following four groups depending on the ventilatory
      mode: (1) Gas ventilation (GV)-control group: GV was continued throughout the
      study; (2) GV-NO group: NO inhalation (10 ppm) was performed under GV; (3) PLV
      control group: PLV using perflubron (15 mL/kg) was continued until the end of the
      study; and (4) PLV-NO group: NO inhalation (10 ppm) was performed under PLV.
      MEASUREMENTS AND RESULTS: NO inhalation improved PaO2 in the PLV-NO group (from
      133+/-20 to 167+/-23 mm Hg; p=0.0008), but not in the GV-NO group (from 67+/-6 to
      63+/-9 mm Hg), although pulmonary vascular resistance decreased both in the GV-NO
      (from 4,604+/-328 to 4,337+/-322 dyne x s x cm(-5); p=0.0116) and the PLV-NO
      group (from 4,727+/-665 to 4,112+/-560 dyne x s x cm(-5); p=0.0036). (Data were
      expressed as mean+/-SEM.) CONCLUSION: PLV augmented the effect of inhaled NO on
      pulmonary gas exchange. The combination of PLV and NO inhalation could be
      effective in severe ARDS.

PMID- 9631809
TI  - Respiratory mechanics after prosthetic reconstruction of the chest wall in normal
      rats.
AB  - OBJECTIVE: Prosthetic reconstruction of the chest wall may yield several
      respiratory changes. Nevertheless, to our knowledge, no comprehensive analysis of
      respiratory mechanics under this condition has been hitherto performed. METHODS:
      Respiratory mechanics were evaluated in two groups of rats. In one group (n=8), a
      polytetrafluoroethylene (PTFE) patch was used; in another group (n=8), a
      polypropylene mesh (Marlex) associated with methylmethacrylate (PPMM) was
      employed. All animals were sedated, anesthetized, paralyzed, and mechanically
      ventilated before and after the prosthetic reconstruction of the chest wall.
      After airway occlusion at end inspiration, respiratory system, pulmonary, and
      chest wall resistive pressures (deltaP1rs, deltaP1L, and deltaP1cw, respectively)
      and viscoelastic/inhomogeneous pressures (deltaP2rs, deltaP2L, and deltaP2cw,
      respectively) were determined. Respiratory system, lung, and chest wall static
      (Est(rs), EstL, and Est(cw), respectively), and dynamic elastances (Edyn(rs),
      EdynL, and Edyn(cw), respectively), and the corresponding delta elastances
      (deltaE, calculated as Edyn-Est) were also obtained. RESULTS: In both groups,
      significant increases in deltaP2rs, deltaP2cw, deltaErs, deltaEcw, Est(rs), EstL,
      and Est(cw) were observed after chest wall reconstruction. However, deltaP2rs,
      deltaP2cw, deltaErs, deltaEcw, Est(rs), and EstL were significantly higher in the
      PPMM group than in the PTFE group. CONCLUSIONS: Prosthetic reconstruction of the
      chest wall yields not only elastic changes, but also there is also an important
      increase of pressure dissipated against viscoelastic/inhomogeneous segments of
      the chest wall. Furthermore, taking into account respiratory mechanics, the PTFE
      patch might be preferred to the PPMM patch.

PMID- 9631810
TI  - Tropical pulmonary eosinophilia.
AB  - Tropical pulmonary eosinophilia (TPE) usually affects people living in the
      tropics, especially those in Southeast Asia, India, and certain parts of China
      and Africa. However, owing to the rising frequency of world-wide travel and the
      migration between continents, this disease is increasingly seen in the West,
      where the diagnosis can be easily missed since it is rarely encountered and can
      mimic many other conditions. Cases of TPE have typically been reported to
      masquerade as acute or refractory bronchial asthma. TPE results from a
      hypersensitivity reaction to lymphatic filarial parasites found in endemic
      regions. There is evidence that it is more likely to occur in nonimmune
      individuals, ie, visitors to endemic regions, than in individuals of endemic
      populations who have developed immunity to filarial infections. Clinical features
      include paroxysmal cough, wheezing and dyspnea, and systemic manifestations such
      as fever and weight loss. A history of residence in a filarial endemic region and
      a finding of peripheral eosinophilia >3,000/mm3 should initiate a consideration
      of this disease. Other criteria for the diagnosis of TPE include absence of
      microfilariae in the blood, high titers of antifilarial antibodies, raised serum
      total IgE >1,000 U/mL, and a favorable response to the antifilarial,
      diethylcarbamazine, which is the recommended treatment. This disease, if left
      untreated or treated late, may lead to long-term sequelae of pulmonary fibrosis
      or chronic bronchitis with chronic respiratory failure. Herein lies the
      importance of early diagnosis and treatment of TPE.

PMID- 9631811
TI  - The "Big Tobacco" settlement: immunity is forever.

PMID- 9631812
TI  - The "Big Tobacco" settlement: the ACCP viewpoint. American College of Chest
      Physicians.

PMID- 9631813
TI  - Metered-dose inhaler to deliver methacholine in bronchial provocation testing: a
      pilot study.
AB  - BACKGROUND: Nonspecific bronchial provocation tests may be simplified by the use
      of hand-held devices to deliver methacholine. OBJECTIVE: To study the feasibility
      of using a metered-dose inhaler (MDI) to administer methacholine in bronchial
      provocation tests, and the ability of such a device to diagnose bronchial
      hyperresponsiveness (BHR) accurately. METHODS: In an open randomized crossover
      pilot study, we compared the provocative dose that induces a 20% fall in FEV1
      (PD20 FEV1) obtained with the methacholine MDI with that obtained using a
      conventional nebulizer in 20 hyperresponsive and 20 nonhyperresponsive subjects.
      The MDI delivers 400 doses of 100 microg of methacholine, and was used via a
      spacer. Bronchial hyperresponsiveness (BHR) was defined as a PD20 FEV1 <2,000
      microg with the conventional test using the nebulizer. The tests were performed
      in each subject in a randomized order, 1 to 7 days apart. RESULTS: Of the
      subjects who had a nebulizer PD20 FEV1 <2,000 microg, all but one had an MDI PD20
      FEV1 <800 microg. When 800 microg was taken as the threshold for the diagnosis of
      BHR with the MDI test, the accuracy of this test to diagnose BHR was 97.5%, and
      the two tests were highly concordant for the diagnosis of BHR (Pearson chi2,
      36.19; p<0.0001). CONCLUSION: A hand-held device may be suitable for delivery of
      methacholine during bronchial provocation tests, if these results are confirmed
      in large samples.

PMID- 9631814
TI  - Use of guidelines in treating community-acquired pneumonia.
AB  - STUDY OBJECTIVES: Guidelines for empiric treatment of community-acquired
      pneumonia (CAP) have been developed to assist in prescribing appropriate
      antimicrobials. We studied utilization of guidelines developed by the American
      Thoracic, Canadian Infectious Diseases, and Canadian Thoracic Societies (ATS,
      CIDS, and CTS, respectively), physicians' familiarity with them, reasons that
      prompt deviation from them, and their effects on clinical outcomes. DESIGN: Two
      part observational study, with prospective and retrospective groups. SETTING: A
      1,100-bed, two-campus, tertiary-care teaching hospital. PATIENTS AND
      PARTICIPANTS: Patients admitted to the general medical ward who were being
      treated empirically for CAP and housestaff who provided their care.
      INTERVENTIONS: Medical residents reported on patients admitted to the hospital
      with CAP. The charts of all unreported patients admitted with CAP over the same
      period were reviewed. MEASUREMENTS AND RESULTS: One hundred twenty-two patients
      were prospectively described and another 130 patients were identified
      retrospectively. There was no difference in guidelines adherence between the
      prospective and retrospective groups (81% compared with 80%; p=0.94). Deviation
      occurred most commonly in suspected aspiration. When physicians believed that
      they were following guidelines, this was true in 88%. When physicians believed
      that they were deviating, they were actually adhering in 46%. Guidelines
      adherence did not alter in-hospital mortality (12% compared with 14%, p=0.92) or
      length of hospitalization (median, 6 days for both groups). CONCLUSIONS:
      ATS/CIDS/CTS guidelines for empiric treatment of CAP are widely used in our
      institution. Future amendments should address aspiration more explicitly.
      Residents' familiarity with them could be improved. Beneficial effects on
      outcomes remain unproven.

PMID- 9631815
TI  - Left ventricular filling pressures during exercise: a cardiological blind spot?

PMID- 9631816
TI  - Radiographic assessment of hyperinflation: correlation with objective chest
      radiographic measurements and mechanical ventilator parameters.
AB  - BACKGROUND: Pulmonary barotrauma is a potentially fatal complication of positive
      pressure ventilation. We previously found that barotrauma occurred in patients
      with radiographic hyperinflation, but few objective data define the relationships
      among hyperinflation, objective chest radiograph (CXR) measurements, ventilator
      parameters, and development of barotrauma. OBJECTIVES: We sought (1) to assess
      the relationships among hyperinflation, objective CXR findings, mechanical
      ventilator parameters, and development of barotrauma. (2) To compare radiographic
      hyperinflation, ventilator parameters, and incidence of barotrauma in a current
      group of ICU patients with historical control subjects. SETTING: Medical and
      surgical ICU patients in a university hospital. DESIGN: Prospective blinded
      observational study; comparison of current series with historical control
      subjects. METHODS: One hundred two prospectively enrolled mechanically ventilated
      medical and surgical ICU patients each received portable supine CXRs that were
      reviewed independently by three radiologists who made objective measurements and
      subjectively determined the likelihood of hyperinflation. Ventilator parameters
      were recorded at the bedside at the time each CXR was obtained. CXR measurements
      and ventilator parameters were then related to the development of barotrauma
      during the course of ventilation and compared with findings of a prospective
      study at our institution 1 year earlier. RESULTS: Radiographically recognizable
      hyperinflation occurred in 18 of 102 mechanically ventilated ICU patients (18%)
      and correlated with lung length (24.7 vs 19.8 cm; p<0.05) and the anterior rib
      number that intersects the hemidiaphragm (5.4 vs 4.7; p<0.05). Patients with
      hyperinflation were ventilated at higher tidal volume per kilogram (VT/kg) (11.0
      vs 9.4; p=0.0081), but peak airway pressure, plateau pressure, and positive end
      expiratory pressure were similar. There were significant decreases in VT (810 vs
      739 mL; p=0.015) and VT/kg (11.0 vs 10.1 mL/kg; p<0.001) in these mechanically
      ventilated ICU patients in comparison to hospital control subjects evaluated
      during the previous year. Paralleling these changes was a decrease in the
      frequency of CXR hyperinflation (p=0.003) and the incidence of ventilator
      associated barotrauma (6.5% vs 0.98%; p=0.048). CONCLUSIONS: Ventilation at
      higher VT/kg is associated with a higher incidence of CXR hyperinflation.
      Radiographic hyperinflation is associated with lung length > or =24.7 cm and
      visualization of the sixth anterior rib. Patients with hyperinflation may be at
      greater risk for developing barotrauma or volutrauma. Ventilatory strategies
      utilizing lower volumes are associated with a lower incidence of such trauma in
      the current sample as compared with historical control subjects.

PMID- 9631817
TI  - Heart or lung disease: determining the primary cause for dyspnea on exertion.

PMID- 9631818
TI  - An unusual case of pseudocardiomegaly.

PMID- 9631819
TI  - Elevated right hemidiaphragm and abdominal pain in a 36-year-old postpartum
      woman.

PMID- 9631820
TI  - Whole-lung lavage in alveolar proteinosis by a modified lavage technique.
AB  - Whole-lung lavage is the only efficient treatment in pulmonary alveolar
      proteinosis. A 36-year-old woman with severe pulmonary alveolar proteinosis
      confirmed by video-assisted thoracoscopic lung biopsies underwent repetitive
      whole-lung lavages without improvement. A modified technique consisting of manual
      ventilation between instillation and aspiration of half the amount of saline used
      for conventional lavage was applied. Impressive clinical and functional
      improvement occurred and persisted for 1 year. We believe that the amelioration
      can be attributed to the technique described above.

PMID- 9631821
TI  - Double jeopardy: lung cancer after cardiac transplantation.
AB  - Two heart transplant patients were referred on the same day for evaluation of new
      chest radiograph abnormalities. Each proved to have advanced stage bronchogenic
      carcinoma. Review of the recent medical literature reveals that the combination
      of profound immunosuppression and a heavy smoking history puts cardiac transplant
      recipients at increased risk for the development of aggressive lung cancers.

PMID- 9631822
TI  - Large airway disease associated with inflammatory bowel disease.
AB  - Lung disease is a rare complication of inflammatory bowel disease (IBD). Herein
      is a series of seven IBD patients who developed new, persistent and unexplained
      symptoms of respiratory disease, particularly chronic productive cough. Using a
      CT scan of the chest, a diagnosis of bronchiectasis was made in five patients,
      while the diagnosis of chronic bronchitis was made in two patients. Factors,
      other than IBD, that could account for pulmonary disease in these patients were
      absent. Several important clinical patterns for IBD-associated large airway
      disease were uncovered and are reviewed in light of earlier case reports in the
      medical literature. A discussion regarding the possible pathogenesis of IBD
      associated airway disease follows.

PMID- 9631823
TI  - Trepopnea due to interatrial shunt following lung resection.
AB  - Dyspnea and platypnea following pneumonectomy have been reported as a result of
      right-to-left interatrial shunt. We report on a case of trepopnea with marked
      positional arterial oxygen desaturation following right middle and lower
      lobectomy. A similar mechanism was found, with right-to-left interatrial shunting
      occurring predominantly in the right lateral position. Surgical repair corrected
      the clinical and physiologic abnormalities.

PMID- 9631824
TI  - Reflections on the revisions in the international system for staging lung cancer.

PMID- 9631825
TI  - Avoiding air in pleural fluid pH samples.

PMID- 9631826
TI  - Bilateral thoracoscopic staple lung volume reduction surgery: Does improvement in
      dyspnea correlate with improvement in pulmonary function?

PMID- 9631827
TI  - Early "profibrotic" or repair activity in the lung during cardiopulmonary bypass:
      who is the culprit?

PMID- 9631828
TI  - Cost-effective pleurodesis.

PMID- 9631829
TI  - Seizures and pulmonary embolism.

PMID- 9631830
TI  - Superior vena cava obstruction in cystic fibrosis.

PMID- 9631831
TI  - Foreign body aspiration into the lower airways may not be unusual in older
      adults.

PMID- 9631832
TI  - Snake bite, rhabdomyolysis, and renal failure.

PMID- 9631833
TI  - Insulin-like growth factor system and the kidney: physiology, pathophysiology,
      and therapeutic implications.
AB  - The insulin-like growth factor (IGF) system, consisting of IGF-I and IGF-II,
      their binding proteins, and their receptors, is expressed in a spatial
      organization in the nephron, but circulating IGFs also affect the kidney. Renal
      and systemic IGF-I and the binding proteins are regulated by growth hormone and
      nutritional status. In the kidney, IGF-I dilates the resistance-regulating
      microvasculature, increases glomerular filtration rate, and promotes tubular
      phosphate and possibly sodium absorption. IGF-I contributes to compensatory renal
      growth in a variety of experimental models and may modestly contribute to
      progressive glomerular sclerosis. In chronic renal failure and the nephrotic
      syndrome, there are several abnormalities in the IGF system. In chronic renal
      failure, IGF-I increases renal function and may improve nutritional status due to
      its anabolic effects. IGF-I accelerates the recovery of renal function in animal
      models of acute renal failure, but results from clinical trials were less
      salutary. Several questions regarding the role of the IGF system in normal and
      abnormal renal biology and potential therapeutic applications in kidney diseases
      remain unanswered.

PMID- 9631835
TI  - Recurrent and de novo renal diseases after renal transplantation: a report from
      the renal allograft disease registry.
AB  - Recurrent or de novo glomerular disease is an important cause of graft
      dysfunction and eventual loss. Cyclosporine A (CyA) has improved short-term renal
      allograft outcome but has not altered long-term graft survival. The purpose of
      the current study is to determine the prevalence of such disease and its impact
      on graft function in the CyA era. From 1984 to 1994, 1,557 renal allografts were
      performed at the Medical College of Wisconsin and the University of Cincinnati.
      Patients were followed up for an average of 7.2 years (minimum, 1 year).
      Recurrent disease was diagnosed by renal biopsy in 98 (6.3%) patients after an
      average of 36 months. Demographic characteristics of patients with and without
      recurrent disease were similar. Glomerulonephritis was the most common finding,
      occurring in 73 patients, and included focal segmental glomerulosclerosis (FSGS),
      25; IgA nephropathy (IgAN), 11; membranous (MN), 11; proliferative, 11;
      membranoproliferative glomerulonephritis (MPGN), 10; glomerular basement membrane
      (anti-GBM), 3; and systemic lupus erythematosus (SLE), two. Diabetic nephropathy
      was present in 22, hemolytic uremic syndrome (HUS) in two, and oxalosis in one.
      Graft loss occurred in 60 of 98 (61%) recipients. Half-life of the allograft was
      diminished in patients with recurrent disease, 2,038 +/- 225 versus 3,135 +/- 385
      days, P = 0.002. The actuarial allograft survival at 1, 3, 5, and 8 years
      posttransplantation with recurrence was 88%, 74%, 57%, and 34%, respectively; and
      the corresponding graft survival for patients without recurrent disease was 80%,
      70%, 64%, and 53%, respectively (P = 0.003). The risk of recurrent disease
      increased with length of graft survival from 2.8% at 2 years to 9.8% and 18.5% at
      5 and 8 years, respectively. We conclude that recurrent disease is a significant
      problem after renal transplantation and is associated with decreased graft
      survival.

PMID- 9631834
TI  - Serologic and virologic profiles of hepatitis C infection in renal transplant
      candidates. New England Organ Bank Hepatitis C Study Group.
AB  - The development of policies to prevent nosocomial transmission of hepatitis C
      virus (HCV) infection in hemodialysis units is critically dependent on the
      understanding of the relationship between tests for anti-HCV, HCV RNA, and HCV
      genotype and the patients' clinical characteristics. We tested sera from all
      patients on the renal transplant waiting list at the New England Organ Bank
      between November 1986 and June 1990 for anti-HCV by a third-generation enzyme
      linked immunosorbent assay (ELISA3) and a third-generation recombinant immunoblot
      assay (RIBA3). All ELISA3-positive sera were tested for HCV RNA by reverse
      transcriptase "nested" polymerase chain reaction, and the genotype was
      characterized by restriction fragment length polymorphism. Sera were available in
      1,544 of 3,243 (48%) patients on the waiting list, of whom 287 (19%) tested
      positive for anti-HCV by ELISA3. Two hundred eighty-six randomly selected, anti
      HCV-negative patients served as controls. Compared with anti-HCV-negative
      controls, anti-HCV-positive patients had a longer duration since initiation of
      renal replacement therapy, higher number of previous kidney transplants and blood
      transfusions, higher proportion of patients with anti-HBc, history of liver
      disease, history of non-A, non-B hepatitis, and elevated serum alanine
      aminotransferase, and lower serum albumin concentrations. Of the 287 anti-HCV
      positive sera, 261 (91%) were reactive by RIBA3, 21 (7%) were indeterminate, and
      five (2%) were nonreactive. HCV RNA was detected in 224 of 275 (81%) ELISA3
      positive patients, in whom additional sera were available. There were no
      significant differences in clinical or laboratory characteristics between ELISA3
      positive patients with and without HCV RNA. Genotypes 1a, 1b, 2a, 2b, 3a, and 4
      were present in 53%, 23%, 8%, 10%, 4%, and 2% of patients, respectively.
      Infection with one, two, or three different HCV genotypes was present in 92%, 7%,
      and 1%, respectively. There was no significant association between the type or
      number of HCV genotypes and RIBA3 reactivity. There were no major differences in
      clinical or laboratory characteristics between genotypes or between single and
      mixed infection. In summary, this study provides detailed information regarding
      the relationship between tests for anti-HCV, HCV RNA, and HCV genotypes and the
      clinical and laboratory characteristics of a large, well-characterized cohort of
      patients referred for renal transplant.

PMID- 9631836
TI  - Follow-up study of children with nephrotic syndrome treated with a long-term
      moderate dose of cyclosporine.
AB  - Because of its potential for chronic nephrotoxicity, the long-term use of
      cyclosporine A (CsA) as treatment for nephrotic syndrome (NS) is controversial.
      The clinical outcome of patients with NS treated with CsA is unclear. We
      retrospectively evaluated 35 children with idiopathic NS, 24 with steroid
      dependent NS (SDNS), and 11 with steroid-resistant NS (SRNS), who received CsA
      therapy for more than 12 months (median, 23 months) at the dosage maintaining 50
      to 120 ng/mL in trough level. For SDNS patients, CsA was added to prednisolone
      after complete remission was achieved. For SRNS patients, CsA was used in
      combination with alternate-day prednisolone. Initial renal histology showed
      minimal changes (MC) in 28 patients (including all of the patients with SDNS) and
      focal segmental glomerulosclerosis (FSGS) in seven patients. The patients were
      followed up for 2 to 10.5 years (median, 6.5 years) after the termination of the
      CsA therapy. In SDNS patients, the relapse rate, dosage of prednisolone, standard
      deviation score for height, and body mass index significantly improved during CsA
      treatment. The follow-up study showed the proportion of SDNS decreased to 13 of
      24 (54%) patients. In SRNS patients, CsA therapy induced remission in 8 of 11
      patients (73%) (complete remission in seven and incomplete remission in one). Six
      of 11 patients (55%) then became steroid sensitive. Post-therapy biopsies,
      performed in 13 patients (10 with SDNS and three with SRNS), showed mild stripped
      interstitial fibrosis in two SDNS patients (15%). Long-term CsA therapy in
      moderate doses was effective to the patients with SDNS and SRNS and low in
      incidence of nephrotoxicity. The long-term use of CsA appears to result in a
      decrease in the proportion of SDNS and acquisition of subsequent steroid
      responsiveness in SRNS.

PMID- 9631837
TI  - Familial amyloid polyneuropathy type I (Portuguese): distribution and
      characterization of renal amyloid deposits.
AB  - Renal amyloidosis has been considered rare and late in the evolution of the
      transthyretin (TTR) familial amyloid polyneuropathy (FAP) of the Portuguese type
      (type I). Renal biopsy has been performed systematically in 14 patients with FAP
      type I before liver transplantation. In all patients, TTR Met30 mutation was
      shown. Seven had proteinuria or abnormal microalbuminuria, whereas seven others
      had no urinary abnormalities. All had renal amyloid deposition predominantly in
      the medulla. Glomerular and vascular involvement was more prominent in patients
      with urinary abnormalities. Patients with the most extensive renal lesions
      represented a subgroup with a low score of polyneuropathy disability, a high
      prevalence of nephropathy in the proband generation, or a late onset for
      relatives with nephropathy. Immunohistochemistry studies showed that the amyloid
      substance corresponded to transthyretin. We have shown that renal TTR-derived
      amyloid deposition is common in patients with FAP type I, even in the absence of
      urinary abnormalities. The clinical presentation of nephropathy is not a late
      occurrence in the disease.

PMID- 9631838
TI  - Overt albuminuria predicts diabetic retinopathy in Hispanics with NIDDM.
AB  - Non-insulin-dependent diabetes mellitus (NIDDM) occurs with a higher frequency in
      Hispanic as compared with non-Hispanic whites. It also appears that there is a
      higher prevalence of diabetic nephropathy in the Hispanic population when
      compared with non-Hispanic whites. In the current study, 144 Hispanics and 671
      non-Hispanic white NIDDM subjects were studied to determine the possible
      association of various risk factors and diabetic complications, including overt
      albuminuria, with diabetic retinopathy. Stereoscopic retinal fundus photographs
      were obtained and graded by the University of Wisconsin Fundus Photographic
      Reading Center. We also sought to determine whether risk factors for retinopathy
      vary between Hispanics and non-Hispanic whites. In the total group, duration of
      diabetes, glycosylated hemoglobin, neuropathy, diastolic hypertension, use of
      insulin, and Hispanic ethnicity correlated with the presence of retinopathy.
      Controlling for severity and duration of diabetes, Hispanics had a significantly
      increased risk of retinopathy relative to non-Hispanic whites (OR = 2.13, 95% CI
      = 1.34, 3.37, P = 0.0013). Duration of diabetes and presence of neuropathy were
      significantly correlated with the presence of diabetic retinopathy in Hispanics
      and non-Hispanic whites. The presence of overt albuminuria (>200 microg/min),
      although not related to diabetic retinopathy in non-Hispanic whites, conferred a
      high risk for diabetic retinopathy in Hispanics (OR = 11.14, CI = 1.20, 103.39, P
      = 0.0339) independent of other risk factors. In summary, Hispanics with NIDDM
      have an increased prevalence of diabetic retinopathy when compared with non
      Hispanic whites. In addition, overt albuminuria in the Hispanic subjects appears
      to be a powerful predictor of the diabetic retinopathy.

PMID- 9631839
TI  - A meta-analysis of the effects of dietary protein restriction on the rate of
      decline in renal function.
AB  - Dietary protein restriction has been reported to delay the need for renal
      replacement therapy in clinical trials and meta-analyses. However, less clear is
      what effect dietary protein has on the rate of decline in renal function. We
      pooled the results of 13 randomized controlled trials (n = 1,919 patients) and
      found that dietary protein restriction reduced the rate of decline in estimated
      glomerular filtration rate by only 0.53 mL/min/yr (95% confidence interval [CI],
      0.08 to 0.98 mL/min/yr). We also used weighted regression analysis to determine
      the reasons for the differences in the results of these 13 randomized trials
      along with 11 other nonrandomized controlled trials (n = 2,248 patients). The
      effect of dietary protein restriction (glomerular filtration rate decline in
      treatment minus control) was substantially less in randomized versus
      nonrandomized trials (regression coefficient, -5.2 mL/min/yr; 95% CI, -7.8 to 
      2.5 mL/min/yr; P < 0.05) and relatively greater among diabetic versus nondiabetic
      patients (5.4 mL/min/yr; 95% CI, 0.3 to 10.5 mL/min/yr; P < 0.05), while there
      was a trend toward a greater effect with each additional year of follow-up (2.1
      mL/min/yr; 95% CI, -0.05 to 4.2 mL/min/yr; P = NS). However, the number of
      diabetic patients studied was small and the duration of follow-up was short in
      most trials. No other patient or study characteristics altered the effect of
      dietary protein restriction on the rate of decline in renal function. Thus,
      although dietary protein restriction retards the rate of renal function decline,
      the relatively weak magnitude of this effect suggests that better therapies are
      needed to slow the rate of renal disease progression.

PMID- 9631841
TI  - Incidence of end-stage renal disease in medically treated patients with severe
      bilateral atherosclerotic renovascular disease.
AB  - Incidence of end-stage renal disease in medically treated patients with severe
      bilateral atherosclerotic renovascular disease. Atherosclerotic renovascular
      disease is an important cause of end-stage renal disease (ESRD). The exact
      incidence of ESRD and the rate of decline in glomerular filtration rate (GFR) in
      patients with this condition is unknown. We report the mortality, the rate of
      decline in renal function, and incidence of ESRD in 51 patients with bilateral
      atherosclerotic renovascular disease followed-up for a median period of 52
      months. None of these patients had undergone any surgical or radiological
      intervention. Renal function was determined by serial measurements of serum
      creatinine. Bilateral atherosclerotic renovascular disease was associated with a
      high mortality rate; the crude mortality rate at 60 months was 45%. Assessment of
      renal function showed impaired renal function at time of angiography and a
      nonuniform and variable decline in renal function during the period of
      observation. The median GFR decreased from 39 mL/min (range, 15 to 80 mL/min) at
      time of angiography to 31 mL/min (range, 10 to 70 mL/min) and 24 mL/min (range,
      10 to 40 mL/min) at 24 and 60 months, respectively (P < 0.05). The calculated
      mean rate of decline in GFR for all patients was 4 mL/min/yr (range, 1 to 16
      mL/min/yr). Over the 5 years, there was a progressive increase in the incidence
      of ESRD. Of the original 51 patients who underwent angiography, six patients
      reached ESRD. The crude incidence of ESRD was, therefore, 12%. Patients who
      reached ESRD were characterized by advanced azotemia at the time of angiography
      (median GFR, 25 mL/min) and a rapid decline in GFR (8 mL/min) compared with
      patients who did not reach ESRD during the observation period (median GFR, 43
      mL/min and an average rate of decline GFR of 3 mL/min).

PMID- 9631840
TI  - Chronicity index and mesangial IgG deposition are risk factors for hypertension
      and renal failure in early IgA nephropathy.
AB  - To determine the natural history in early immunoglobulin A (IgA) nephropathy, we
      evaluated the long-term follow-up of 27 normotensive nonazotemic adult idiopathic
      IgA nephropathy patients with chronic hematuria who derived from a prospective
      regional epidemiological study of glomerulonephritis conducted between 1978 and
      1984. As controls, 17 thin glomerular basement membrane (GBM) patients, 24
      patients with normal renal tissue, and nine patients with miscellaneous
      nephropathies were followed up. Median follow-up was 11 years (range, 8 to 14
      years). Renal biopsies, performed within 2 years after patient identification,
      were scored semiquantitatively in terms of activity and chronicity indices, using
      a modified National Institutes of Health (NIH) scoring system. During follow-up,
      two patients with IgA nephropathy went into histological remission, and 12 IgA
      nephropathy patients showed disease progression, of whom three developed renal
      failure. Initial proteinuria over 1 g/d was associated with a high activity
      score, extracapillary lesions, and late onset of uremia. Mesangial IgG deposition
      and a higher initial chronicity index were associated with development of
      hypertension during follow-up. In the multivariate analysis, a high initial
      chronicity index, erythrocyturia, and mesangial IgG deposition are independent
      determinants of progression of disease. We conclude that in patients with IgA
      nephropathy, identified early in the course of disease, erythrocyturia, a high
      chronicity index, and mesangial IgG deposition in the presence of normal renal
      function are risk factors for decreased renal survival. Disappearance of
      hematuria is associated with remission of IgA nephropathy immunopathologically
      and low activity and chronicity indices at initial biopsy.

PMID- 9631842
TI  - Autoantibodies to polymorphonuclear neutrophil elastase do not inhibit but
      enhance elastase activity.
AB  - Polymorphonuclear neutrophils (PMNs) of patients with active Wegener's
      granulomatosis and PMN activated in vitro express elastase on their surface as
      detected by autoantibodies derived from patients with ANCA-positive vasculitis or
      chronic staphylococcus infections. The PMN-associated elastase was enzymatically
      active. By affinity-purified autoantibodies to elastase, the enzymatic activity
      was further enhanced as measured either by a chromogenic peptide or by elastin as
      substrate. Antibodies to human elastase from mouse or from sheep also enhanced
      elastase activity, whereas unrelated immunoglobulins had no effect. Taken
      together, our data indicate that autoantibodies to elastase are not inhibitory
      but upregulate the elastase activity and thereby might contribute to tissue
      damage.

PMID- 9631843
TI  - Determination of the solute removal index for urea by using a partial spent
      dialysate collection method.
AB  - In 22 hemodialysis patients, during a dialysis session, the solute removal index
      (SRI) for urea obtained from the use of a partial spent dialysate collection
      method was compared with that derived from the use of a total spent dialysate
      collection technique. The partial spent dialysate collection method was used to
      harvest a small representative sample of the total spent dialysate. The volumes
      of spent dialysate collected by the partial and the total spent dialysate
      collection methods were 1.7 +/- 0.4 L and 129.6 +/- 15.3 L, respectively. The
      total amount of urea nitrogen removed by dialysis as estimated by the partial
      spent dialysate collection method was similar to that determined by the total
      spent dialysate collection approach. As a result, the SRI value for urea obtained
      by the partial spent dialysate collection method (namely, 63% +/- 8%) correlated
      very well (r = 0.95, P < 0.001) with that derived by the total spent dialysate
      collection technique (namely, 62% +/- 8%). Our data suggest that it is feasible
      to use a simple partial spent dialysate collection method to obtain SRI results
      in patients treated with hemodialysis.

PMID- 9631844
TI  - Incidence, outcome, and risk factors of cerebrovascular events in patients
      undergoing maintenance hemodialysis.
AB  - We retrospectively investigated the incidence and prognosis of and risk factors
      for cerebrovascular events in 1,064 patients with chronic uremia who received
      maintenance hemodialysis (HD) for more than 3 months during 24 years in our
      dialysis units in Miyazaki, Japan. Cerebrovascular events developed in 98
      patients (9.2%). The confirmed incidences of cerebral hemorrhage (CH) and
      infarction were 8.7 and 3.7 per 1,000 patient-years, respectively. Of the 56
      patients with CH, 40 (71.4%) died within 3 months of the onset of CH. Ganglio
      thalamic lesion was observed in 32 (80.0%) of 40 patients with CH confirmed by a
      brain computed tomography. The incidence of polycystic kidney disease was higher
      in the CH group than in the overall HD population (12.5% v 3.9%, P < 0.01). Of
      the 13 patients with diabetes mellitus and nephrosclerosis, nine (69.2%)
      developed CH within 36 months of the initiation of HD; 11 (78.6%) of 14 patients
      with chronic glomerulonephritis developed CH after 36 months. CH developed in six
      patients (15.0%) within 6 hours of a previous HD session. We compared laboratory
      values, the supine blood pressure, and electrocardiographic (ECG) findings in 35
      patients with CH and a control group (66 patients) matched in age, sex, basal
      renal disease, age at the initiation of HD, and the duration of HD. Data were
      obtained before and after HD 3 to 4 months before the first attack of CH. The
      systolic and diastolic blood pressure (SBP, DBP) before and after HD were
      significantly higher in the CH group than in the control group (pre-HD SBP: 171
      +/- 22.5 v 154 +/- 19.3 mm Hg, P < 0.001; pre-HD DBP: 89 +/- 13.6 v 81 +/- 9.6 mm
      Hg, P < 0.001). The incidence of left ventricular hypertrophy was higher, and the
      Kt/V was significantly lower (1.23 +/- 0.26 v 1.38 +/- 0.34, P < 0.05) in the CH
      group than in the control group. However, there were no significant differences
      in the serum levels of albumin and cholesterol or the total dose of heparin
      during HD sessions between groups. In conclusion, the incidence of CH was high,
      and its prognosis was poor, in patients undergoing maintenance HD. Reversible
      risk factors include hypertension and possibly the amount of HD prescribed, but
      not anticoagulation with heparin.

PMID- 9631845
TI  - Simple nutritional indicators as independent predictors of mortality in
      hemodialysis patients.
AB  - A strong association exists between nutritional status and morbidity and
      mortality in patients with end-stage renal disease who are treated with
      hemodialysis. Described here is the predictive value for mortality over 5 years
      of follow-up of a number of risk factors, recorded at baseline, in a national
      sample of 3,607 hemodialysis patients. Among the variables studied were case-mix
      covariates, caregiver classifications of nutritional status, serum albumin
      concentration, and body mass index (BMI). The Case Mix Adequacy special study of
      the United States Renal Data System (USRDS) provided these measurements as of
      December 31, 1990. The USRDS patient standard analysis file provided follow-up
      data on mortality for all patients through December 31, 1995, by which time 64.7%
      of the patients had died. BMI is a simple anthropometric measurement that has
      received little attention in dialysis practice. Caregiver classification refers
      to documentation in a patient's dialysis facility medical records that stated an
      individual to be "undernourished/cachectic," "obese/overweight," or "well
      nourished." The mean serum albumin was 3.7 +/- 0.45 (SD) g/dL, and the mean BMI
      was 24.4 +/- 5.3 (SD) kg/m2. By caregiver classification, 20.1% of patients were
      undernourished, and 24.9% obese. In hazard regression models, including but not
      limited to the Cox proportional hazards model, low BMI, low serum albumin, and
      the caregiver classification "undernourished" were independently and
      significantly predictive of increased mortality. In analyses allowing for time
      varying relative mortality risks (ie, nonproportional hazards), the greatest
      predictive value of all three variables occurred early during follow-up, but the
      independent predictive value of baseline serum albumin and BMI measurements on
      mortality risk persisted even 5 years later. No evidence of increasing mortality
      risk was found for higher values of BMI. Serum albumin was confirmed to be a
      useful predictor of mortality risk in hemodialysis patients; BMI was established
      as an independently important predictor of mortality; both serum albumin and BMI,
      measured at baseline, continue to possess predictive value 5 years later; the
      subjective caregiver classification of nutritional status "undernourished" has
      independent value in predicting mortality risk beyond the information gained from
      two other markers of nutritional status--BMI and serum albumin.

PMID- 9631846
TI  - Postdialysis fatigue: lack of effect of a biocompatible membrane.
AB  - Tumor necrosis factor-alpha (TNF-alpha) has been shown to have somnogenic
      properties. Plasma levels of this cytokine have been found to increase
      significantly during dialysis with a bioincompatible (cuprophane) membrane in
      patients with postdialysis fatigue (PDF). We conducted a crossover study with
      random assignment to ascertain whether a biocompatible membrane might attenuate
      the increase of TNF-alpha and severity of PDF. Sixteen patients on maintenance
      hemodialysis underwent dialysis with either cuprophane (n = 8) or
      polymethylmethacrylate (PMMA; n = 8) membranes for 1 week and then switched to
      the opposite membrane during the second week. Predialysis and postdialysis
      measurements of plasma TNF-alpha levels were performed during the first and last
      dialysis treatments of each week. A fatigue score was determined from the sum of
      duration of fatigue and sleep within 6 hours of the completion of dialysis. TNF
      alpha levels increased by an average of 18.3% during dialysis with cuprophane
      membranes but only 2.4% with PMMA membranes (P = 0.04). Despite this, fatigue
      scores remained unaltered (approximately 4 of 6). Hence, the biocompatible
      membrane, PMMA, failed to alleviate PDF. This suggests that dialytic stimulation
      of TNF-alpha plays no substantial role in the pathogenesis of PDF.

PMID- 9631847
TI  - Biostat 1000 and Daugirdas blood-based hemodialysis quantification: agreement and
      reproducibility.
AB  - Agreement and reproducibility of Daugirdas blood-based and Biostat 1000 dialysate
      based Kt/V estimation were explored. Fifty-two dialysis treatments in 19 patients
      were studied. All patients were dialyzed by arteriovenous (AV) access. Good
      agreement was found in the comparison between laboratory predialysis blood urea
      nitrogen (BUN) and Biostat 1000 BUN. Each treatment was assessed for Kt/V
      simultaneously by Biostat 1000 and by Daugirdas methods based on predialysis and
      postdialysis BUN. Four Daugirdas blood-based Kt/V estimations per session were
      obtained; two were single pool Kt/V, the first using an "arterial" postdialysis
      BUN and the second a "mixed venous" postdialysis BUN, whereas the other two were
      double pool (or equilibrated) eKt/V obtained by factoring the respective single
      pool "arterial" and "mixed venous" Kt/V for the relative rate of solute removal.
      The four blood-based and Biostat 1000 Kt/V were examined for pooled-within
      patient variability in 15 of the patients in whom three dialysis sessions on the
      same dialysis prescription were available, and these were not significantly
      different between the blood-based and Biostat 1000 Kt/V. The four blood-based
      Kt/V were then compared with the Biostat 1000 Kt/V using the concordance
      correlation coefficient (CC, 1 indicating pairs of observations fall on a line of
      identity, 0 indicating no relationship), and bias and range of agreement as
      defined by the Bland and Altman technique of analysis. The "mixed venous" eKt/V
      had the closest agreement with the Biostat 1000 Kt/V (CC = 0.77), but the range
      of agreement as defined by Bland and Altman was 0.62, implying that for a single
      session, there was a 95% chance that the "mixed venous" eKt/V would lie within +/
      0.31 of the Biostat 1000 Kt/V. It is concluded that Biostat 1000 Kt/V results
      are comparable in large groups to certain Daugirdas blood-based Kt/V, although
      for a given dialysis session, clinically important differences in resulting Kt/V
      parameters may be seen between these two methods of estimating Kt/V.

PMID- 9631848
TI  - Determinants of vancomycin clearance by continuous venovenous hemofiltration and
      continuous venovenous hemodialysis.
AB  - The clearance of vancomycin is significantly reduced in patients with acute, as
      well as, chronic renal failure. Although multiple-dosage regimen adjustment
      techniques have been proposed for these patients, there is little quantitative
      data to guide the individualization of vancomycin therapy in acute renal failure
      patients who are receiving continuous renal replacement therapy (CRRT). To
      determine appropriate vancomycin dosing strategies for patients receiving
      continuous venovenous hemofiltration (CVVH) and continuous venovenous
      hemodialysis (CVVHD), we performed controlled clearance studies in five stable
      hemodialysis patients with three hemofilters: an acrylonitrile copolymer 0.6 m2
      (AN69), polymethylmethacrylate 2.1 m2 (PMMA), and polysulfone 0.65 m2 (PS).
      Patients received 500 mg of vancomycin intravenously at least 12 hours before the
      start of the clearance study. The concentration of vancomycin in multiple plasma
      and dialysate/ultrafiltrate samples was determined by EMIT (Syva, Palo Alto, CA).
      The diffusional clearance and sieving coefficient (SC) of vancomycin were
      compared by a mixed-model repeated-measures analysis of variance (ANOVA) with
      filter and blood (Q(B)), dialysate inflow (Q(DI)), or ultrafiltration rate
      (Q(UF)) as the main effects and patient as a random effect. Vancomycin was
      moderately protein bound in these patients; free fraction ranged from 49% to 83%.
      The SCs of the three filters were similar and significantly correlated with the
      free fraction of vancomycin (P = 0.01; r2 = 0.465). Significant linear
      relationships were observed between the diffusional clearance of vancomycin and
      Q(DI) for all three filters: AN69 (slope = 0.482; r2 = 0.880); PMMA (slope =
      0.853; r2 = 0.966); and PS (slope = 0.658; r2 = 0.887). The slope of this
      relationship for the PMMA filter was significantly greater than that of the AN69
      and PS filters. The clearance of vancomycin, urea, and creatinine, however, was
      essentially constant at all Q(B)s for all three filters. Thus, the clearance of
      vancomycin was not membrane dependent during CVVH. However, during CVVHD,
      membrane dependence of vancomycin clearance was noted at a Q(DI) greater than
      16.7 mL/min; vancomycin clearance with PMMA at a Q(DI) of 25 mL/min was 66% and
      43% greater than that with the AN69 and PS filters, respectively. CVVH (62% to
      262%) and CVVHD (90% to 540%) can significantly augment the clearance of
      vancomycin in acute renal failure patients. Dosing strategies for
      individualization of vancomycin therapy in patients receiving CVVH and CVVHD are
      proposed.

PMID- 9631849
TI  - "Beer potomania" in non-beer drinkers: effect of low dietary solute intake.
AB  - A ovolactovegetarian patient presented with hyponatremia. She had maximally
      dilute urine and undetectable vasopressin levels. Dietary history revealed very
      low protein intake but no beer intake. We postulated that the very low intake of
      solute limited her water excretion and caused the hyponatremia despite only a
      modest increase in fluid intake. When protein intake was increased in a clinical
      research center setting, free water excretion increased and serum sodium
      normalized despite maintaining the water intake at 4 to 5 L daily. We discuss the
      role of dietary solute in water excretion. Previously described in beer drinkers,
      the phenomenon can occur in the absence of beer drinking. In this era of weight
      consciousness, hyponatremia because of low solute intake may be seen with
      increased frequency.

PMID- 9631850
TI  - MPO-ANCA-positive crescentic necrotizing glomerulonephritis and
      tubulointerstitial nephritis with renal eosinophilic infiltration and peripheral
      blood eosinophilia.
AB  - We present the case of a 67-year-old woman with myeloperoxidase (MPO)
      antineutrophil cytoplasmic antibody (ANCA)-positive pauci-immune crescentic
      necrotizing glomerulonephritis and tubulointerstitial nephritis with renal
      eosinophilic infiltration and peripheral blood eosinophilia. Staining for
      eosinophil cationic protein indicated that activated eosinophils were involved in
      the tubulitis, as well as in the glomerular injury. Marked peripheral blood
      eosinophilia is uncommon in ANCA-positive crescentic necrotizing
      glomerulonephritis associated with tubulointerstitial nephritis, except in Churg
      Strauss syndrome. However, our patient had no clinical history or signs of
      asthma, no other signs suggestive of allergic diseases, and no histologic
      findings of granulomas in the kidney, thus failing to fulfill the criteria for
      Churg-Strauss syndrome.

PMID- 9631851
TI  - Facilitated diagnosis of the contiguous gene syndrome: tuberous sclerosis and
      polycystic kidneys by means of haplotype studies.
AB  - Tuberous sclerosis (TSC) and autosomal dominant polycystic kidney disease (ADPKD)
      are genetically heterogeneous diseases. The major gene for ADPKD (PKD1) lies
      adjacent to the TSC2 gene on chromosome 16p13. Some reports in the literature
      referred to an unusual presentation of TSC with enlarged cystic kidneys at birth,
      but it was not until the localization of the TSC2 and PKD1 genes that it was
      possible to analyze the interaction between both genes. We describe a case of a
      child with TSC and enlarged cystic kidneys. The study of genetic marker
      segregation in the family pointed to the presence of a deletion involving the 3'
      region of PKD1. A further study of the region showed a deletion of 40 kb
      involving both PKD1 and TSC2. We suggest that an additive or synergistic effect
      between PKD1 and TSC2 may cause this renal phenotype. A contiguous gene syndrome
      involving PKD1 and TSC2 should be suspected in children with TSC and enlarged
      polycystic kidneys at birth. The first approach to identify a deletion of both
      genes could be the analysis of the segregation of PKD1 and TSC2 markers in the
      family.

PMID- 9631852
TI  - Renal failure in giant cell vasculitis.
AB  - A 59-year-old white woman with temporal arteritis developed progressive renal
      failure. Renal biopsy results showed focal and segmental necrotizing
      glomerulonephritis; furthermore, giant cells were present in the destructed
      vessel walls. Immunosuppressive therapy did not prevent terminal renal failure.
      This case shows that renal involvement may be a feature of temporal arteritis.

PMID- 9631853
TI  - Rate of progression of renal disease and low-protein diet.

PMID- 9631854
TI  - Optimizing solute clearance and fluid balance with high-fill volumes: effect of
      hypertonic dialysate.

PMID- 9631855
TI  - Monoclonal gammopathy in a type II diabetic: a case of determined significance.

PMID- 9631856
TI  - Chemotactic factors and renal inflammation.
AB  - The mechanisms of leukocyte entry into the kidney during inflammatory renal
      disease have recently received considerable attention. Chemotactic factors appear
      to play a central role in this process, not only by inducing leukocyte movement
      but also by enhancing endothelial and leukocyte adhesiveness and endothelial
      permeability. The evidence supporting the role of chemotactic factors in renal
      inflammation comes from three types of studies. (1) Cell culture studies have
      shown that renal parenchymal cells produce chemotactic factors in response to
      proinflammatory stimuli. (2) Immunohistochemical and in situ hybridization
      analyses of renal tissue from patients or experimental animals have demonstrated
      local renal expression of chemotactic factors in association with inflammatory
      disease. (3) Experiments designed to neutralize the chemoattractant activity of
      specific chemotactic factors in leukocyte-dependent models of renal injury have
      shown an attenuation of inflammatory infiltrates and a decrease in indices of
      renal damage. In this article, these data are reviewed for complement-derived
      chemotactic factors, the leukocyte-specific chemokines, and the interstitial
      chemoattractant osteopontin, and the possibilities of therapeutic interventions
      based on abrogating chemoattractant expression or function in human renal disease
      are considered.

PMID- 9631857
TI  - Definitions of acute rejection and controlled clinical trials in the medical
      literature.
AB  - Definitions of acute rejection for clinical trial use would allow for
      standardized comparison of outcomes. The medical literature reporting trial
      results was searched to record definitions used in controlled trials. Over 6,000
      refereed transplantation articles were searched for the following keywords:
      randomized controlled trials, multicenter studies, clinical trials, phase III,
      and immunosuppressive agents. Only three references resulted. Another pass
      through the literature resulted in 11 prospective studies on induction therapy
      and two prospective antirejection therapy studies that met the criteria for the
      search. Retrospective studies appearing in the literature search were two
      induction citations and seven antirejection therapy reports. Rejection criteria
      ranged from having been given no definition in both outcomes of induction trials
      as well as reports on antirejection therapy to having a large-scale list of
      criteria not all of which had to be met by every rejection case in a given study
      to be termed rejection. The transplant literature that was reviewed frequently
      provided only vague descriptions of the methodologies used to diagnose rejection
      and rejection reversal. The Efficacy Endpoints Conference on Kidney Transplant
      Rejection was formulated to review kidney transplant rejection using a database
      of consecutive rejection episodes. An attempt to derive definitions for clinical
      trial endpoints in kidney transplant rejections was planned for the conference
      because of a lack of continuity in the transplant literature.

PMID- 9631858
TI  - Tacrolimus (FK506) and the pharmaceutical/academic/regulatory gauntlet.
AB  - The pivotal issue of transplant rejection diagnosis and management is design,
      conduct, and analysis of clinical trials. The historical experience with clinical
      trials of major immunosuppressive drugs (cyclosporine and especially tacrolimus)
      is examined in this article. Cyclosporine was a turning point in transplantation,
      providing an extraordinary improvement over previous therapies. Additionally,
      early investigational experience with tacrolimus was shown to be important in
      rescue from cyclosporine failure. Experience with tacrolimus in liver recipients
      for primary therapy led to understanding that the side effect profile was similar
      to cyclosporine and that the important side effects of tacrolimus (toxicity and
      diabetes) could be lessened by altering the drug dose. Early dosing regimens were
      determined by attempts to balance the toxicities (representing a dose ceiling)
      against rejection (for minimum dosing). Drug levels became understandable and
      trough levels could be used to guide therapy. However, when the multicenter liver
      trial was implemented, high starting doses were included in the protocol design,
      ignoring information obtained with drug level monitoring. Disregard for this
      information led to a distortion of the potential value of tacrolimus. Historical
      controls from the Pittsburgh experience suggested that tacrolimus was a critical
      immunosuppressant, and the randomized trial against cyclosporine confirmed the
      drug's ability to compete. The multicenter liver trial, however, was not balanced
      across treatment arms for other immunosuppressive agents (ie, higher doses of
      prednisone from center to center, additional induction protocols at various
      centers). Additionally, analysis of study results differed across continents, and
      the role of tacrolimus in cyclosporine rescue was not examined thoroughly. When
      tacrolimus was proposed for use in extrahepatic organ transplantation, again the
      Pittsburgh experience, as well as experience from other single centers, was
      determined inadequate evidence of efficacy, and randomized trials were required
      by the FDA. The fact that multicenter trials in transplantation have historically
      been poorly designed or analyzed weighed against the dramatic improvements shown
      from historically controlled studies or single-center trials should lead to
      question of the regulatory requirement for multicenter randomized trials for all
      organ types.

PMID- 9631859
TI  - Importance of allograft biopsy in renal transplant recipients: correlation
      between clinical and histological diagnosis.
AB  - Renal allograft dysfunction after transplantation may be caused by acute
      rejection (AR), chronic rejection (CR), cyclosporine (CyA) or tacrolimus (FK)
      toxicity, and other causes such as recurrence of renal disease. Allograft biopsy
      is the "gold standard" to establish the correct diagnosis. However, many
      transplant centers routinely do not consider graft biopsy at the onset of renal
      dysfunction; instead, empirical steroid therapy or CyA dose reduction is the
      initial response to graft dysfunction. In this study, we prospectively predicted
      the histological findings prior to renal biopsy and correlated the clinical and
      histological diagnoses after the final report was issued by the pathologist.
      Patients with renal dysfunction after transplantation (increased serum creatinine
      >20% from baseline) were submitted to allograft biopsy. Three clinicians (C1, C2,
      and C3) involved in the care of these patients independently predicted the
      histological findings prior to the biopsy. A total of 100 cases (62 men, 38
      women; 71 whites, 29 blacks) with a mean age of 41 years (21 to 70 years) were
      included in this study. Biopsy samples were taken after a mean period of 1.6 +/-
      0.32 years (median, 0.25 years; range, 4 days to 17 years) after transplantation.
      Two patients with en bloc pediatric kidneys required postbiopsy blood
      transfusions for self-limiting bleeding; all other patients had no complications.
      All patients received azathioprine and prednisone; additionally, 74 received CyA
      and 19 FK. Final histopathologic diagnoses were AR (30), CyA/FK toxicity (36), AR
      plus CyA/FK toxicity (17), CR (11), recurrent disease (11), and other (6). In 28
      cases (28%), the results of the biopsies showed more than one diagnosis. A
      completely correct diagnosis was predicted by C1, C2, and C3 in 47%, 42%, and 41%
      (mean, 43%) of the cases, incorrect diagnosis in 25%, 27%, and 25% (mean, 26%) of
      the cases, and partially correct diagnosis in 28%, 31%, and 34% (mean, 31%) of
      the cases, respectively. AR was confirmed histologically in 26 of 47 cases (55%)
      in the presence of therapeutic or high CyA/FK blood levels, whereas in 41 of 53
      cases (77%), the histology showed CyA/FK toxicity in the presence of therapeutic
      or low CyA/FK blood levels. The mean serum creatinine at the time of the biopsy
      was 2.92 +/- 0.30 mg/dL, compared with the baseline of 1.76 +/- 0.10 mg/dL (P <
      0.0001). After appropriate treatment, mean serum creatinine was 2.38 +/- 0.33
      mg/dL (P < 0.0001). These data show that clinical prediction was poor, with
      totally correct diagnosis in only 43% of the cases. In 26%, the diagnosis was
      incorrect. We conclude that the renal biopsy is essential for establishing the
      correct diagnosis of renal allograft dysfunction and the appropriate management
      thereof.

PMID- 9631860
TI  - Role of renal allograft biopsy in multicenter clinical trials in transplantation.
AB  - There is current agreement that in the design of prospective clinical trials,
      patients should be assigned to various treatment groups based on histological
      diagnosis of acute renal allograft rejection. The Banff schema is satisfactory in
      reporting and grading histology for patient entry into clinical trials,
      particularly in multicenter studies because it standardizes the entry and
      randomization criteria and maintains reproducibility of the histological
      Interpretation between the different centers. It should be emphasized that for
      biopsy specimens to be effective tools for either clinical practice or clinical
      trials, they need to be obtained before therapeutic intervention and handled by
      experienced histopathology laboratory technicians. Adequate tissue sampling is
      necessary for diagnosis and for proper grading of rejection. It is recommended
      that a minimum of two cores of renal tissue are needed to avoid underestimation
      of rejection grade. Banff classification considers a biopsy specimen to be
      adequate if it contains seven or more glomeruli and at least a single artery.
      Examination of serial step sections through the tissue samples is crucial to
      identify focal lesions of toxicity and to properly score intimal arteritis and
      tubulitis. In addition, fast interpretation of the biopsy by an experienced
      nephropathologist or a transplant pathologist within 24 hours optimizes the
      utilization of the biopsy-acquired information. At the present time, it is
      premature to decide on the role of graft histology as an endpoint in clinical
      trials, but posttreatment biopsies should be encouraged in large, multicenter,
      prospective trials because they may be our only tools to study postrejection
      changes. Semiquantitative biopsy reporting systems should be routinely included
      in clinical databases to allow for the prospective examination of structure
      function relationships and long-term outcomes following acute rejection.

PMID- 9631861
TI  - Efficacy Endpoints Conference on Acute Rejection in Kidney Transplantation:
      review of the conference questionnaire.
AB  - Basic differences in the diagnosis and management of acute rejection in renal
      transplant can be found between centers. A questionnaire was developed to
      ascertain the profile of these variables. Sixteen fundamental questions were
      presented to the program directors of 17 transplant groups from around the world.
      The questions were brief and designed to identify clinical practice and behaviors
      related to the definition of acute and steroid-resistant rejection, successful
      response to therapy, use of histological diagnosis, estimated frequency of
      rejection, and frequency of mild, moderate, or severe acute rejections.
      Clinicians were presented with case studies and asked to respond to specific
      questions regarding the rejection management described in these cases to
      determine similarities in management practices. Results indicated that clinicians
      relied on clinical symptoms only rarely. Biopsy findings were used by 53% of
      clinicians, and 94% of clinicians indicated that rejection was suspected if
      creatinine increased. Successful response was defined as a return to prerejection
      creatinine level by 77% of clinicians and that steroid-resistant rejection is
      evident by 5 days. Biopsy was used by 80% of centers to diagnose first acute
      rejection episode, and only 18% of rejection episodes are expected to be severe.
      This report was then used to develop a more detailed questionnaire to be used in
      profiling acute rejection in consecutive transplant recipients.

PMID- 9631862
TI  - Efficacy Endpoints Conference on Acute Rejection in Kidney Transplantation:
      summary report of the database.
AB  - An international database of rejection episodes and their characteristics with
      regard to definition and follow-up parameters was developed to improve the
      approach to protocol development for clinical trials. Nineteen North American,
      European, and Australian centers uniformly reported on 50 consecutive transplant
      rejection episodes. Data collected included patient demographic parameters,
      induction and maintenance immunosuppression therapies, rejection agents (drug,
      dose, duration), clinical signs (50% decrease in urine, fever), serum creatinine
      (nadir, at rejection, daily during antirejection therapy to 15 days, and days 30,
      90, 180, and 365 after rejection date), histopathological findings, morbidity,
      recurrence of rejection, and function at 1 year. The centers contributed a total
      of 953 presumed rejection episodes, of which 842 were confirmed as acute
      rejection episodes. The majority of cases were first rejections (81%), and
      rejection occurred 119 +/- 345 days following transplantation. The Banff Schema
      of histological grading was used in 38% of biopsy-proven rejection episodes (2%
      Borderline, 42% Grade I, 38% Grade II, 18% Grade III). Only 30% of all rejections
      showed clinical signs that were most likely to occur in Grade III rejection
      episodes (P < 0.006). The serum creatinine response was well below the rejection
      creatinine level by day 15 following initiation of antirejection therapy in the
      majority of cases. A significant number of the cases (34%) reported in this
      database experienced a recurrent rejection approximately 85 days following the
      first rejection. Graft survival 1 year following the rejection episode was good
      (83%). These findings will facilitate development of clinical trial design and
      beneficially impact approaches to antirejection therapies for kidney allograft
      recipients.

PMID- 9631863
TI  - Proposed consensus for definitions and endpoints for clinical trials of acute
      kidney transplant rejection.
AB  - Progress in transplantation therapeutics requires validation from multicenter
      trials in which enrollment criteria and endpoint definitions have been
      standardized. A database of acute rejection was established from 19 North
      American, European, and Australian transplant centers and included parameters on
      rejection diagnosis and treatment of 50 consecutive rejection episodes from each
      center. Patient demographics, induction and maintenance immunosuppressive
      therapies, antirejection agents (drug, dose, duration), clinical signs (decrease
      in urine volume, presence of fever of > or =38.5 degrees C), serum creatinine
      concentration (nadir, at rejection, daily during antirejection therapy to 15
      days, and days 30, 90, 180, and 365 after rejection date), rejection biopsy
      findings, morbidity, recurrence of rejection, and renal function at 1 year were
      recorded for 953 rejection episodes. From these data, three definitions were
      proposed. Acute rejection was defined as an immunologic process resulting in a
      serum creatinine increase of > or =0.4 mg/dL, with or without clinical signs, and
      should include a biopsy confirmation that has been standardized to the Banff
      criteria. Corticosteroid-resistant rejection was defined as a rejection episode
      in which a minimum of 250 to 1000 mg of methylprednisolone administered as
      initial therapy fails to result in stabilization or reduction of the serum
      creatinine after 3 days of corticosteroid treatment. Successful response to
      therapy was defined as a serum creatinine level < or =110% of the serum
      creatinine on the day of the rejection diagnosis and a return of the serum
      creatinine to or below the rejection creatinine level by 5 days of therapy with
      maintenance of this response for a minimum of 30 days. The work represented in
      the Efficacy Endpoints Database provides a step toward improving definitions in
      clinical trials. Continuity in clinical trial design should lead to improvements
      in evaluation of outcomes and, thereby have an effect on clinical practice.

PMID- 9631865
TI  - Tracking a tangled PATH. Physicians At Teaching Hospitals.

PMID- 9631864
TI  - Observations on recovery of renal function following treatment for acute
      rejection.
AB  - The characteristics of rejection and rejection response have not been
      systematically described in renal transplant recipients. The Efficacy Endpoints
      Conference Database contains characteristics from 953 episodes of rejection
      occurring at 19 North American, European, and Australian transplant centers. This
      database was used to profile renal transplant rejection episodes treated with
      primary steroid therapy, primary antilymphocyte antibody therapy, and rescue
      antilymphocyte antibody therapy. Primary steroid therapy was used in 88% of the
      rejection episodes. A successful response was more common in recipients without
      fever (72% v 61%; P < 0.004), in recipients experiencing less than a Banff Grade
      III rejection (92% v 75%; P = 0.009), and was more likely associated with graft
      function at 1 year following the rejection than rejection episodes that failed
      steroid therapy (89% v 82%; P = 0.013). Steroid success was statistically
      identifiable by day 2 of therapy and clinically useful by day 3; serum creatinine
      on these days of therapy is shown as a ratio of the rejection creatinine (102% v
      112% day 1, success v failure, P< 0.002; 104% v122% day 2, success v failure, P <
      0.0001; 105% v125% day 3, success vfailure, P < 0.0001). Response to primary
      antilymphocyte antibody therapy reached significance at day 5 of therapy when
      serum creatinine decreased below the rejection creatinine level in antilymphocyte
      successes but remained at or above the rejection creatinine in those who failed
      the therapy (90% v 135%; P < 0.01). For rescue antilymphocyte antibody therapy, a
      response was evident after 5 days of therapy (approximately day 9 to 10 of
      rejection) when serum creatinine began to decline and continued lower throughout
      the 10-day course of antilymphocyte antibody therapy (day 14 to 15 of rejection;
      serum creatinine 3.0 mg/dL v 4.4 mg/dL for success v failure; P < 0.004). Serum
      creatinine was lower throughout the first year following therapy in each success
      group (steroids, antilymphocyte antibody therapy as primary or as rescue), and a
      greater percentage of failures of any of the three therapies resulted in graft
      loss. Interestingly, 1-year graft survival was not different in the patients who
      were treated with antilymphocyte antibody therapy as primary than those who
      received these antirejection agents as rescue therapy (81% and 84%,
      respectively). The Efficacy Endpoints Conference Database provides an essential
      tool for profiling acute rejection in renal transplantation and should lead to
      improved evaluation of rejection therapies.

PMID- 9631866
TI  - ACE inhibitors in acute myocardial infarction: patient selection and timing.

PMID- 9631867
TI  - Antiphospholipid syndrome in the elderly: caution.

PMID- 9631868
TI  - Estrogen modulates AT1 receptor gene expression in vitro and in vivo.
AB  - BACKGROUND: The AT1 receptor has been implicated in the pathogenesis of
      hypertension and atherosclerosis. Estrogen deficiency is also associated with
      cardiovascular diseases. Therefore, we examined the AT1 receptor gene expression
      in ovariectomized rats with and without estrogen replacement therapy and the
      influence of estrogen on AT1 receptor expression in cultured vascular smooth
      muscle cells. METHODS AND RESULTS: Rat aortic tissue was examined 5 weeks after
      ovariectomy. In one group, estrogen (1.7 mg estradiol) was administered during
      the 5-week period. Functional experiments assessed angiotensin II-induced
      contraction of aortic rings. AT1 receptor mRNA levels were measured by
      quantitative polymerase chain reaction and Northern blotting. AT1 receptor
      density was assessed by radioligand binding assays. These techniques were also
      applied in cultured vascular smooth muscle cells. The efficacy of angiotensin II
      on vasoconstriction was significantly increased in aortas from ovariectomized
      rats. As assessed by radioligand binding assays, AT1 receptor density was
      increased to 160% without changes in receptor affinity during estrogen
      deficiency. AT1 receptor mRNA levels were consistently increased to 187% in
      ovariectomized rats compared with sham-operated animals. Estrogen substitution
      therapy in ovariectomized rats reversed this AT1 receptor overexpression. To
      explore the underlying mechanisms, the direct influence of estradiol on AT1
      receptor expression was investigated in VSMCs. Estradiol (1 micromol/L) led to a
      time-dependent downregulation of AT1 receptor mRNA, with a maximum of 33.3% at 12
      hours. There was a correlative decrease in AT1 receptor density. CONCLUSIONS:
      This novel observation of estrogen-induced downregulation of AT1 receptor
      expression could explain the association of estrogen deficiency with hypertension
      and atherosclerosis, because activation of the AT1 receptor plays a key role in
      the regulation of blood pressure, fluid homeostasis, and vascular cell growth.

PMID- 9631869
TI  - Indications for ACE inhibitors in the early treatment of acute myocardial
      infarction: systematic overview of individual data from 100,000 patients in
      randomized trials. ACE Inhibitor Myocardial Infarction Collaborative Group.
AB  - BACKGROUND: Several large-scale trials have demonstrated improved survival with
      ACE-inhibitor therapy started during acute myocardial infarction. A systematic
      overview was conducted to resolve uncertainties regarding time of initiation,
      time course of effect, and identification of patients in whom the benefits or the
      risks may be greater. METHODS AND RESULTS: This overview aimed to include
      individual data from all randomized trials involving more than 1000 patients in
      which ACE-inhibitor treatment was started in the acute phase (0 to 36 hours) of
      myocardial infarction and continued for a short time (4 to 6 weeks). Data were
      available for 98,496 patients from 4 eligible trials, and the results were
      consistent among the trials. Thirty-day mortality was 7.1% among patients
      allocated to ACE inhibitors and 7.6% among control subjects, corresponding to a
      7% (SD, 2%) proportional reduction (95% CI, 2% to 11%; 2P<0.004). This
      represented avoidance of approximately 5 (SD, 2) deaths per 1000 patients, with
      most of the benefit observed within the first week. The proportional benefit was
      similar in patients at different underlying risk. The absolute benefit was
      particularly large in some high-risk groups (ie, Killip class 2 to 3, heart rate
      > or = 100 bpm at entry) and in anterior MI. ACE-inhibitor therapy also reduced
      the incidence of nonfatal cardiac failure (14.6% versus 15.2%, 2P=0.01) but was
      associated with an excess of persistent hypotension (17.6% versus 9.3%, 2P<0.01)
      and renal dysfunction (1.3% versus 0.6%, 2P<0.01). CONCLUSIONS: These results
      support the use of ACE inhibitors early in the treatment of acute MI, either to a
      wide range of patients or selectively in patients with anterior MI and in those
      at increased risk of death.

PMID- 9631870
TI  - Increased plasminogen activator inhibitor type 1 in coronary artery atherectomy
      specimens from type 2 diabetic compared with nondiabetic patients: a potential
      factor predisposing to thrombosis and its persistence.
AB  - BACKGROUND: Inhibition of fibrinolysis attributable to elevated concentrations of
      plasminogen activator inhibitor type 1 (PAI-1) in blood is associated with
      insulin resistance, hyperinsulinemia, and type 2 diabetes mellitus. Because we
      have shown that insulin can stimulate PAI-1 synthesis in vivo and because
      accelerated vascular disease is common in such patients as well, we hypothesized
      that increased PAI-1, potentially predisposing to thrombosis, acute occlusion,
      and accelerating atherosclerosis because of thrombus-associated mitogens, would
      be present in excess in atheroma from type 2 diabetic subjects. METHODS AND
      RESULTS: Samples acquired by directional coronary atherectomy from 25 patients
      with type 2 diabetes and 18 patients without diabetes were characterized
      qualitatively histologically for cellularity and by immunohistochemistry visually
      and qualitatively and by quantitative image analysis for assessment of urokinase
      type plasminogen activator (u-PA) and PAI-1. Patients with and without diabetes
      were similar with respect to demographic features and the distribution and
      severity of coronary artery disease. Substantially more PAI-1 and substantially
      less u-PA were present in the atherectomy samples from subjects with diabetes.
      CONCLUSIONS: The disproportionate elevation of PAI-1 compared with u-PA observed
      in atheromatous material extracted from vessels of diabetic subjects is
      consistent with increased gene expression of PAI-1 in vessels as well as the
      known increase of PAI-1 in blood, presumably reflecting increased synthesis. The
      increased PAI-1 detected in the atheroma may contribute in vivo to accelerated or
      persistent thrombosis underlying acute occlusion and to vasculopathy exacerbated
      by clot-associated mitogens in the vessel wall. Because the changes were observed
      to be associated with insulin resistance and type 2 diabetes mellitus, they may
      be modifiable by reduction of insulin resistance with insulin sensitizers and
      stringent control of hyperglycemia.

PMID- 9631871
TI  - Vitamin C improves endothelium-dependent vasodilation by restoring nitric oxide
      activity in essential hypertension.
AB  - BACKGROUND: Essential hypertension is associated with impaired endothelium
      dependent vasodilation. Inactivation of endothelium-derived nitric oxide by
      oxygen free radicals participates in endothelial dysfunction in experimental
      hypertension. To test this hypothesis in humans, we evaluated the effect of
      antioxidant vitamin C on endothelium-dependent responses in essential
      hypertensive patients. METHODS AND RESULTS: In 14 healthy subjects (47.1+/-4.8
      years; blood pressure, 120.6+/-4.5/80.9+/-3.5 mm Hg) and 14 essential
      hypertensive patients (47.3+/-5.1 years; blood pressure, 153.9+/-7.1/102.3+/-4.1
      mm Hg), we studied forearm blood flow (strain-gauge plethysmography)
      modifications induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, and
      15 microg x 100 mL(-1) x min(-1)) or sodium nitroprusside (1, 2, and 4 microg/100
      mL forearm tissue per minute), an endothelium-dependent and -independent
      vasodilator, respectively, in basal conditions and during infusion of
      intrabrachial vitamin C (2.4 mg/100 mL forearm tissue per minute). In
      hypertensive patients but not in control subjects, vitamin C increased (P<0.01)
      the impaired vasodilation to acetylcholine, whereas the response to sodium
      nitroprusside was unaffected. Moreover, in another 14 hypertensive patients
      (47.1+/-5.2 years; blood pressure, 155.2+/-6.9/103.7+/-4.5 mm Hg), the
      facilitating effect of vitamin C on vasodilation to acetylcholine was reversed by
      N(G)-monomethyl-L-arginine (100 microg/100 mL forearm tissue per minute), a
      nitric oxide synthase inhibitor, suggesting that in essential hypertension
      superoxide anions impair endothelium-dependent vasodilation by nitric oxide
      breakdown. Finally, because in adjunctive 7 hypertensive patients (47.8+/-6.1
      years; blood pressure, 155.3+/-6.8/103.5+/-4.3 mm Hg), indomethacin (50
      microg/100 mL forearm tissue per minute), a cyclooxygenase inhibitor, prevented
      the potentiating effect of vitamin C on vasodilation to acetylcholine, it is
      possible that in essential hypertension a main source of superoxide anions could
      be the cyclooxygenase pathway. CONCLUSIONS: In essential hypertensive patients,
      impaired endothelial vasodilation can be improved by the antioxidant vitamin C,
      an effect that can be reversed by the nitric oxide synthase inhibitor N(G)
      monomethyl-L-arginine. These findings support the hypothesis that nitric oxide
      inactivation by oxygen free radicals contributes to endothelial dysfunction in
      essential hypertension.

PMID- 9631872
TI  - Clinical features and prognostic implications of familial hypertrophic
      cardiomyopathy related to the cardiac myosin-binding protein C gene.
AB  - BACKGROUND: Little information is available on phenotype-genotype correlations in
      familial hypertrophic cardiomyopathy that are related to the cardiac myosin
      binding protein C (MYBPC3) gene. The aim of this study was to perform this type
      of analysis. METHODS AND RESULTS: We studied 76 genetically affected subjects
      from nine families with seven recently identified mutations (SASint20, SDSint7,
      SDSint23, branch point int23, Glu542Gln, a deletion in exon 25, and a
      duplication/deletion in exon 33) in the MYBPC3 gene. Detailed clinical, ECG, and
      echocardiographic parameters were analyzed. An intergene analysis was performed
      by comparing the MYBPC3 group to seven mutations in the beta-myosin heavy-chain
      gene (beta-MHC) group (n=52). There was no significant phenotypic difference
      among the different mutations in the MYBPC3 gene. However, in the MYBPC3 group
      compared with the beta-MHC group, (1) prognosis was significantly better
      (P<0.0001), and no deaths occurred before the age of 40 years; (2) the age at
      onset of symptoms was delayed (41+/-19 versus 35+/-17 years, P<0.002); and (3)
      before 30 years of age, the phenotype was particularly mild because penetrance
      was low (41% versus 62%), maximal wall thicknesses lower (12+/-4 versus 16+/-7
      mm, P<0.03), and abnormal T waves less frequent (9% versus 45%, P<0.02).
      CONCLUSIONS: These results are consistent with specific clinical features related
      to the MYBPC3 gene: onset of the disease appears delayed and the prognosis is
      better than that associated with the beta-MHC gene. These findings could be
      particularly important for the purpose of clinical management and genetic
      counseling in familial hypertrophic cardiomyopathy.

PMID- 9631873
TI  - Age- and sex-related differences in clinical manifestations in patients with
      congenital long-QT syndrome: findings from the International LQTS Registry.
AB  - BACKGROUND: Unexplained female predominance is observed in long-QT syndrome
      (LQTS), a congenital autosomal disorder with prolonged repolarization and syncope
      or sudden death due to ventricular tachyarrhythmias. Our objectives were to
      evaluate age- and sex-related differences in events among LQTS patients referred
      to the LQTS International Registry. METHODS AND RESULTS: Age- and sex-related
      occurrence of events was analyzed in 479 probands (70% females) and 1041 affected
      family members (QTc >440 ms, 58% females). LQTS-gene mutations were identified in
      162 patients: 69 LQT1 carriers (KVLQT1 on 11p15.5), 62 LQT2 carriers (HERG on
      7q35-36), and 31 LQT3 carriers (SCN5A on 3p21-24). Females predominated among 366
      probands (71% females) and 230 symptomatic family members (62% females). Male
      probands were younger than females at first event (8+/-7 versus 14+/-10 years,
      P<0.0001) and had higher event rates by age 15 years than females (74% versus
      51%, P<0.0001). Affected family members had similar findings. By Cox analysis
      adjusting for QTc duration, the hazard ratio for female probands of experiencing
      events by age 15 years was 0.48 (P<0.001), and it was 1.87 (P=0.09) by age 15 to
      40 years. In female family members, the hazard ratio was 0.58 (P<0.001) by age 15
      years, and it was 3.25 (P<0.001) by age 15 to 40 years. The event rate was higher
      in male than female LQT1 carriers (69% versus 32%, P=0.001). No age-sex
      difference in event rate was detected in LQT2 and LQT3 carriers. CONCLUSIONS:
      Among LQTS patients, the risk of cardiac events was higher in males until puberty
      and higher in females during adulthood. The same pattern was evident among LQT1
      gene carriers. Unknown sex factors modulate QT duration and arrhythmic events,
      with preliminary evidence of gene-specific differences in age-sex modulation.

PMID- 9631874
TI  - Ventriculophasic modulation of atrioventricular nodal conduction in humans.
AB  - BACKGROUND: Baroreceptor-mediated phasic changes in vagal tone have been
      hypothesized to cause ventriculophasic sinus arrhythmia (VPSA). The objectives of
      this study were to demonstrate ventriculophasic modulation of AV nodal conduction
      and to substantiate the role of the baroreflex on ventriculophasic AV nodal
      conduction (VPAVN) by pharmacological perturbation of parasympathetic tone.
      METHODS AND RESULTS: Twelve patients with infra-Hisian second-degree heart block
      and VPSA were studied. Incremental atrial pacing was performed until AV nodal
      Wenckebach block at baseline, after phenylephrine infusion, and after atropine.
      AV nodal conduction curves were constructed for each phase and compared. At
      baseline, VPAVN was present in 9 of 12 patients on the steep portion of the AV
      nodal conduction curves. Phenylephrine increased systolic blood pressure from
      149+/-33 to 177+/-22 mmHg (P<0.001) and sinus cycle length from 844+/-169 to
      1010+/-190 ms (P<0.001) and shifted the AV nodal conduction curves up and to the
      right. Phenylephrine induced VPAVN in 2 of 3 patients in whom it was not present
      at baseline and in 11 of 12 total. Atropine abolished both VPSA and VPAVN in all
      patients. CONCLUSIONS: VPAVN was demonstrated in patients with infra-Hisian
      second-degree AV block. It was accentuated by phenylephrine and abolished by
      atropine, suggesting a baroreflex mechanism for VPSA and VPAVN.

PMID- 9631875
TI  - Application of serial in vivo magnetic resonance imaging to evaluate the efficacy
      of endothelin receptor antagonist SB 217242 in the rat carotid artery model of
      neointima formation.
AB  - BACKGROUND: Alleviating vascular restenosis after percutaneous transluminal
      angioplasty remains a formidable challenge. Although multiple factors have been
      implicated in the pathophysiology of this vascular remodeling disorder, only
      limited therapeutic success has been achieved. Endothelin (ET)-1 has recently
      been implicated in the pathogenesis of neointimal growth. We report the in vivo
      efficacy of SB 217242, a nonpeptide dual ET(A)/ET(B) receptor antagonist with
      high oral bioavailability, in the rat carotid artery balloon angioplasty model.
      METHODS AND RESULTS: The lumen volumes of carotid arteries were estimated
      serially with magnetic resonance imaging (MRI) at baseline and at day 7 and day
      14 after balloon catheter-induced denudation of the carotid arterial wall in the
      rat. Histomorphometric analysis was performed at day 14 after surgery to
      quantitate intimal hyperplasia. Statistical analysis was performed with ANOVA
      followed by post hoc Newman-Keuls multiple comparison test. In comparison to
      vehicle-treated animals, a 20% protection (P<0.05) from reduction was shown in
      the estimated lumen volume with long-term administration of SB 217242 (15 mg/kg
      BID p.o.). Histologic analyses indicated a 42% decrease (P<0.05) in neointimal
      growth. The MRI lumen volumes had a significant correlation with the
      corresponding histologic indices. CONCLUSIONS: Serial MRI provides the
      opportunity to assess the progression of vascular lumen volume in vivo after
      balloon angioplasty. MRI measurements can, in conjunction with in vitro
      histologic measurements, contribute to the understanding of the actions of
      pharmacologic agents in experimental models of neointima formation. With the use
      of serial MRI and histologic measurements, it is demonstrated that protection
      from both lumen volume reduction and neointima formation is obtained in this
      model by use of a potent, nonpeptide dual ET(A)/ET(B) receptor antagonist, SB
      217242. Furthermore, this study provides additional support to the implication of
      ET-1 in the pathophysiology of neointima formation.

PMID- 9631876
TI  - Myocardial infarction and apoptosis after myocardial ischemia and reperfusion:
      role of the terminal complement components and inhibition by anti-C5 therapy.
AB  - BACKGROUND: Myocardial ischemia and reperfusion (MI/R)-induced tissue injury
      involves necrosis and apoptosis. However, the precise contribution of apoptosis
      to cell death, as well as the mechanism of apoptosis induction, has not been
      delineated. In this study, we sought to define the contribution of the activated
      terminal complement components to apoptosis and necrosis in a rat model of MI/R
      injury. METHODS AND RESULTS: Monoclonal antibodies (mAbs; 18A and 16C) raised
      against the rat C5 complement component bound to purified rat C5 (ELISA). 18A
      effectively blocked C5b-9-mediated cell lysis and C5a-induced chemotaxis of rat
      polymorphonuclear leukocytes (PMNs), whereas 16C had no complement inhibitor
      activity. A single dose (20 mg/kg i.v.) of 18A blocked >80% of serum hemolytic
      activity for >4 hours. Administration of 18A before myocardial ischemia (30
      minutes) and reperfusion (4 hours) significantly reduced (91%) left ventricular
      free wall PMN infiltration compared with 16C treatment. Treatment with 18A 1 hour
      before ischemia or 5 minutes before reperfusion significantly reduced infarct
      size compared with 16C treatment. A significant reduction in infarct size (42%)
      was also observed in 18A-treated rats after 30 minutes of ischemia and 7 days of
      reperfusion. DNA ladders and DNA labeling (eg, TUNEL assay) demonstrated a
      dramatic reduction in MI/R-induced apoptosis in 18A-treated compared with 16C
      treated rats. CONCLUSIONS: Anti-C5 therapy in the setting of MI/R significantly
      inhibits cell apoptosis, necrosis, and PMN infiltration in the rat despite C3
      deposition. We conclude that the terminal complement components C5a and C5b-9 are
      key mediators of tissue injury in MI/R.

PMID- 9631878
TI  - Images in cardiovascular medicine. Electrocardiographic diagnosis of acute
      myocardial infarction during ventricular pacing.

PMID- 9631877
TI  - Mechanism of beta-adrenergic receptor upregulation induced by ACE inhibition in
      cultured neonatal rat cardiac myocytes: roles of bradykinin and protein kinase C.
AB  - BACKGROUND: Although bradykinin is thought to contribute to the effects of ACE
      inhibitors on the cardiovascular system, its precise role remains to be
      elucidated. Evidence suggests that bradykinin might be important in the
      upregulation of beta-adrenergic receptors (beta-ARs) induced by ACE inhibitors,
      and the role of bradykinin in this effect has now been investigated with cultured
      neonatal rat cardiac myocytes. METHODS AND RESULTS: The density of beta-ARs on
      the myocyte surface was determined with a binding assay with [3H]CGP-12177.
      Incubation of cultured myocytes for 24 hours with the ACE inhibitor captopril (1
      micromol/L) increased beta-AR density by 35% and enhanced the response of cells
      to isoproterenol but not to forskolin. Neither an angiotensin-II type 1 (AT1)
      receptor antagonist, CV-11974, nor angiotensin-I affected beta-AR density.
      However, the bradykinin B2 receptor antagonist Hoe 140 abolished the effect of
      captopril on beta-AR upregulation in a dose-dependent manner. The protein kinase
      C inhibitor staurosporine (20 nmol/L) but neither indomethacin nor L-NAME also
      inhibited captopril-induced upregulation of beta-ARs. Exogenous bradykinin
      increased the spontaneous beating frequency of cultured myocytes and Hoe 140
      abolished this effect. Bradykinin level in the medium increased 1.4-fold by the
      treatment of cultured myocytes with captopril for 24 hours. CONCLUSIONS: The
      results suggest that captopril enhances beta-AR responsiveness by inducing beta
      AR upregulation and that the latter effect is mediated by activation of
      bradykinin B2 receptors and protein kinase C. These observations also offer
      insight into the different roles of ACE inhibitors and AT1 receptor antagonists
      in the treatment of heart failure.

PMID- 9631879
TI  - Images in cardiovascular medicine. Ectasia and aneurysm of the right coronary
      artery resulting from a shunt to the coronary sinus.

PMID- 9631880
TI  - Glucose-insulin-potassium therapy for treatment of acute myocardial infarction.

PMID- 9631881
TI  - Adenosine pretreatment of human myocardium and ischemic preconditioning.

PMID- 9631882
TI  - Dexamethasone downregulates L-selectin in vitro and in vivo.

PMID- 9631883
TI  - Intracoronary Doppler and collateral resistance.

PMID- 9631884
TI  - Recommendations for cardiovascular screening, staffing, and emergency policies at
      health/fitness facilities.

PMID- 9631885
TI  - Cardiovascular preparticipation screening of competitive athletes: addendum: an
      addendum to a statement for health professionals from the Sudden Death Committee
      (Council on Clinical Cardiology) and the Congenital Cardiac Defects Committee
      (Council on Cardiovascular Disease in the Young), American Heart Association.

PMID- 9631886
TI  - Constitutive endothelial nitric oxide synthase (ecNOS) gene expression in human
      monocytes.
AB  - This study evaluates using a polymerase chain reaction (PCR)-based molecular
      biological approach to study the gene expression of the constitutive endothelial
      isoform of nitric oxide synthase (ecNOS) in human monocytes. When PCR was carried
      out with specific primers for ecNOS, 302 bp product was amplified, which sequence
      analysis determined as having 100% identity to the reported human ecNOS isoform
      gene sequence. The data presented here demonstrate a reliable technique for
      assessing ecNOS mRNA levels in circulating human monocytes. This then permits use
      of this easily available cell to monitor ecNOS levels and provides a means to
      investigate mechanisms involved in controlling NO synthase levels as well as NO
      synthesis.

PMID- 9631887
TI  - Reduced number of circulating monocytes after institution of insulin therapy-
      relevance for development of atherosclerosis in diabetics?
AB  - Twelve patients with Type II diabetes mellitus, insufficiently controlled with
      oral hypoglycemic agents, were studied before, after 2 months, and after 4 months
      on insulin therapy. For comparison the same variables were also studied in 10
      healthy subjects. From the start, in the diabetic group, the authors found
      alterations in the hemorheologic parameters indicated by increased values for
      whole blood viscosity, plasma viscosity, red cell transit time (RCTT), and
      decreased values for white cell initial relative filtration rate (IrFR). In
      hematologic parameters they found increased values for mean corpuscular volume
      (MCV), leukocyte count, counts of neutrophils and monocytes, and a decreased
      count of lymphocytes. They also found increased values in the lipid parameters P
      triglycerides and Apo B/Apo A-I ratio, risk factors of coronary atherosclerosis.
      After 4 months of insulin treatment whole blood and plasma viscosity were still
      increased, but there was a partial improvement of lipoprotein abnormalities. Red
      and white cell filterability, however, tended to normalize. These results
      indicate that changes in blood cell filterability do not necessarily influence in
      vitro measurements of blood viscosity. The change in RCTT during the insulin
      treatment was associated with a decreased MCV and the change in white cell IrFR
      with a decrease in the number of monocytes. This change of white cell
      filterability during insulin therapy, probably due to a reduced number of
      monocytes, may be of interest in the study of atherosclerosis and circulatory
      disease in diabetics.

PMID- 9631888
TI  - Safety of endovascular treatment in high-cardiac-risk patients with limb
      threatening ischemia.
AB  - Vascular surgery can be safely performed in approximately 60% of patients with
      advanced peripheral vascular disease, because of the high frequency of
      concomitant coronary artery disease and consequent increased risk of
      perioperative cardiac complications. The aim of this study was to validate the
      hypothesis that endovascular revascularization could be safely applied to high
      cardiac-risk patients with a lower incidence of perioperative cardiac
      complications. One hundred and fourteen patients with peripheral vascular disease
      referred for revascularization underwent preoperatively a clinical and
      echocardiographic evaluation, at rest and under dipyridamole stress test, to
      assess the cardiac risk. Patients with high clinical score (according to Goldman
      and Detsky), or low left ventricular ejection fraction at rest, or positive
      dipyridamole stress test, were considered at high cardiac risk. To record adverse
      cardiac events, all patients were monitored during surgery, postoperatively, and
      followed up for 18 months after hospital discharge. Forty-eight patients (42%)
      were found to be at high cardiac risk. In this high-cardiac-risk group,
      endovascular surgery was performed in 37/48 patients (77%) (group A), while the
      remaining 11/48 patients (23%) were bypassed with open surgery (group B).
      Postoperative cardiac complications occurred in 16% of patients in group A and in
      45% of patients in group B with two deaths (p < 0.05). At follow-up, 51% of
      patients in group A and 44% of patients in group B had suffered late cardiac
      events (p=ns), with 10 deaths in group A and three deaths in group B (p=ns). Limb
      salvage rate was similar in the two groups (95% group A, 100% group B; p=ns).
      These data show that high-cardiac-risk patients with limb-threatening ischemia
      have significantly less perioperative cardiac complications when treated by
      endovascular procedures instead of bypass surgery. Follow-up data on cardiac
      events confirm the severity of concomitant coronary artery disease in patients
      with peripheral vascular disease.

PMID- 9631889
TI  - Blood flux and venoarteriolar response of the skin in legs with chronic venous
      insufficiency measured at two different depths by using a double-wavelength laser
      Doppler technique.
AB  - The laser Doppler flux (LDF) and the venoarteriolar response (VAR) of the skin in
      legs with chronic venous insufficiency (CVI) was measured by using a new double
      wavelength probe technique (543 nm and 780 nm). The recordings were taken in a
      recumbent and in a sitting position. Ten patients with CVI and 20 control
      subjects with healthy legs were investigated. The LDF was found to be
      significantly enhanced in a recumbent position at 543 nm and in a sitting
      position at 780 nm in legs with CVI compared with healthy legs (P<0.05 and
      P=0.02, respectively). The authors could not find the VAR to be impaired in
      either wavelength in legs with CVI compared with healthy legs. The double
      wavelength probe technique makes it possible to record simultaneously the LDF in
      the superficial and deep layers of the skin on the same place in the leg.

PMID- 9631890
TI  - Mechanism of rethrombosis after thrombolytic therapy: angioscopic findings and
      investigation of the coagulation system in dogs.
AB  - The purpose of this study was to angioscopically observe the process of
      thrombolysis after intracoronary administration of thrombolytic agents and to
      investigate the effects of these agents on coagulation/fibrinolysis systems in
      dogs. The coronary endothelium was removed and thrombus formation was confirmed
      by angioscopy. In the tissue plasminogen activator (tPA) group (n=8), complete
      thrombolysis occurred in all animals, but thrombolysis was incomplete in the
      urokinase (UK) group (n=6). The plasma level of plasmin alpha2-plasmin inhibitor
      complex peaked at 15 minutes after treatment in both the tPA and UK groups.
      Plasma thrombin-antithrombin III (TAT) complex decreased transiently at 15
      minutes after tPA administration but increased at 30 and 60 minutes (P<0.05). In
      the UK group, plasma TAT also showed a transient decrease followed by an
      increase, which was minimal compared with that in the tPA group. Plasma TAT
      decreased transiently after infusion of tPA and subsequently increased to above
      the pretreatment level, suggesting a risk of rethrombosis after successful
      recanalization.

PMID- 9631891
TI  - Silent myocardial ischemia after myocardial infarction: severity of coronary
      artery disease, impact on left ventricular systolic and diastolic functions and
      prognosis.
AB  - The aim of the present study was assessment of the relationship of silent
      myocardial ischemia with clinical, coronary angiography findings, and left
      ventricular systolic and diastolic function, and its prognostic significance in
      patients early after myocardial infarction. One hundred nineteen male patients
      (mean age 48.2+/-1.2 years) with first Q wave myocardial infarction entered the
      study. Routine coronary angiography, 24-hour Holter electrocardiographic
      recordings, and two-dimensional and Doppler echocardiography with assessment of
      left ventricular systolic and diastolic function were performed in all the
      patients. Prospective follow-up was done during 1 year. Patients with signs of
      silent myocardial ischemia early after myocardial infarction had more severe
      coronary artery disease, pronounced disturbances of left ventricular systolic and
      diastolic performance, and adverse prognosis than those without ischemia
      appearance during Holter recordings.

PMID- 9631892
TI  - Comparison of the three different formulas for Doppler estimation of pulmonary
      artery systolic pressure.
AB  - Noninvasive pulmonary artery systolic pressure (PASP) is calculated by summing
      the right ventricular systolic pressure obtained from Doppler velocity of
      regurgitant flow through the tricuspid valve and the right atrial (RA) pressure.
      The RA pressure is generally assumed from different formulas. An accurate RA
      pressure estimation will add precision to PASP calculation. One of the methods to
      estimate RA pressure is the inferior vena cava collapsibility index (IVCCI). In
      45 patients referred for right heart catheterization, the authors tested a
      formula for the calculation of PASP based on the estimation of RA pressure from
      IVCCI and compared this method with two other formulas. The first method (method
      1) assumed a constant RA pressure of 10 mm Hg irrespective of right ventricular
      pressure. The formula used was Doppler gradient + 10 (mm Hg). In the second
      method (method 2), a clinical estimate of RV pressure was made from the formula:
      right ventricular-right atrial Doppler gradient x 1.1 + 14. In the third method
      (method 3), the patients were classified into three groups on the basis of IVCCI:
      group A, IVCCI greater than 45%; group B, IVCCI between 35% and 45%; and group C,
      IVCCI less than 35%. The formula used was Doppler gradient + 6, 9, or 16 mm Hg in
      the presence of normal (group A), moderately reduced (group B), or markedly
      reduced (group 3) IVCCI. A good correlation between Doppler and catheter
      measurements of PASP was found for methods 1, 2, and 3, respectively (r=0.8933,
      SEE=6.4, r=0.8921, SEE=7.0, and r=0.8989, SEE=6.7). Correlation between invasive
      and noninvasive PASP was similar with the three methods, but correlation in
      method 2 was less satisfactory than with the other two methods. The mean
      difference between Doppler-derived and hemodynamic PASP was also high in method
      2. In conclusion, the result of this study validates a relatively new, simple
      echo-Doppler formula for Doppler estimation of PASP based on a noninvasive
      evaluation of RA pressure through the IVCCI. However, this method is not better
      than the traditional method 1 for noninvasive PASP estimation.

PMID- 9631893
TI  - Nailfold capillaroscopy in hypothyroidism and hyperthyroidism: blood flow
      velocity during rest and postocclusive reactive hyperemia.
AB  - Direct intravital microscopic examinations of nailfold capillaries were made in
      three groups of subjects: 15 healthy volunteers (C) and 11 patients, six with
      hypothyroidism (h) and five with hyperthyroidism (H). The groups h and H were
      examined twice, before the onset of treatment and when they returned to
      euthyroidism. Capillary blood flow velocity (CBFV) was measured during rest and
      after release of 60-second arterial occlusion. To assess autoregulatory capacity
      the authors determined peak CBFV postocclusion and time to reach it in single
      capillaries. In patients with hypothyroidism, before the onset of the treatment,
      the mean resting and the mean peak CBFV were significantly lower (resting CBFV
      group C: 0.93+/-0.11 mm/s (mean+/-SE); group h: 0.33+/-0.09 mm/s; and mean peak
      CBFV-group C: 1.49+/-0.14 mm/s; group h: 0.79+/-0.19 mm/s). The time to reach
      mean peak CBFV postocclusion was significantly prolonged (group C: 8.9+/-0.65 s
      and group h: 19.2+/-2.0 s) compared with the group of healthy volunteers. When
      these patients achieved euthyroidism, all the studied parameters returned to
      control levels. In patients with hyperthyroidism only minor changes in CBFV could
      be detected. In patients with hypothyroidism, the skin microvascular
      autoregulatory mechanisms are disturbed. The impairments of the reactive
      hyperemia response could be correlated with the control of the disease (thyroid
      state).

PMID- 9631894
TI  - Cerebral vascular accidents in young patients with essential thrombocythemia:
      relation with other known cardiovascular risk factors.
AB  - BACKGROUND AND PURPOSE: Since the advent of routine automated blood cell counts,
      an increased platelet count often is detected fortuitously in asymptomatic
      individuals. In the past, essential thrombocythemia (ET) was thought to be linked
      to an increase incidence of hemorrhagic complications, whereas thrombosis is now
      considered more frequently. Actually, the risk of thrombosis cannot be predicted
      in an asymptomatic patient with essential thrombocythemia. PATIENTS AND METHODS:
      A total of 41 young patients (age range, 18 to 45 years) affected by ET and
      diagnosed in agreement with the Polycythemia Vera Study Group criteria are
      reported. Common risk factors, such as hypertension, smoke, obesity,
      dyslipidemia, and diabetes, have been registered. Particular attention has been
      given to cerebral vascular accidents (CVA) both of the arterial and venous
      systems. Platelet number, platelet serotonin content, and platelet aggregation
      under collagen, adenosine diphosphate (ADP), and adrenalin stimuli were
      evaluated. RESULTS: Nine out of the 41 patients affected by ET had CVAs, four of
      which occurred in the venous system. No difference in platelet function tests has
      been observed between patients with or without CVA. Six out of the 9 patients
      with ET and CVA had at least one atherosclerotic risk factor: four were heavy
      smokers, one had hypertension, and one had hypertension and obesity. CONCLUSIONS:
      Cerebral vascular accidents are confirmed to be frequent in patients with
      essential thrombocythemia, even at a young age. However, the presence of at least
      one atherosclerotic risk factor associated with increased platelet number seems
      to favor thrombotic complications. In particular, cigarette smoking seems to be
      related to arterial CVAs in essential thrombocythemia.

PMID- 9631895
TI  - Coronary artery slow flow associated with angina pectoris and hypotension--a case
      report.
AB  - A 56-year-old woman with a history of angina pectoris developed substernal chest
      pressure and hypotension during coronary angiography. Her baseline coronary
      angiogram appeared normal. During this episode, injection of contrast medium into
      the left coronary artery demonstrated coronary artery slow flow in the left
      anterior descending artery and branches of the circumflex coronary artery, which
      normalized following the sublingual administration of nitroglycerin. There were
      no focal areas of coronary artery spasm. This phenomenon may represent a
      heretofore undescribed mechanism for myocardial ischemia and its sequelae.

PMID- 9631896
TI  - Thromboangiitis obliterans (Buerger's disease) with intestinal involvement--a
      case report.
AB  - Thromboangiitis obliterans (TAO) or Buerger's disease is a nonatherosclerotic
      vascular disease of unknown etiology that occurs almost exclusively in young male
      tobacco users. The involvement of the medium-sized and small arteries and veins
      leads to ischemic complaints and trophic changes in the limbs. The authors report
      a case of Buerger's disease in a 29-year-old man, a heavy smoker, affecting the
      lower limbs and mesenteric vessels.

PMID- 9631897
TI  - Successful treatment of ergotism with Iloprost--a case report.
AB  - A 34-year-old woman was hospitalized for severe acute arterial insufficiency of
      the limbs. Overuse of ergotamine derivative was acknowledged by the patient, who
      had a long history of migraine headaches. An arteriogram showed diffuse arterial
      spasm and occlusion of right leg distal arteries. Intravenous infusion of a
      stable prostacyclin analog (Iloprost) was administered. Rapid and complete
      improvement of arteriospasm was noted within a few hours, confirmed by a further
      arteriogram. This appears to be one of the rare case reports of successful limb
      salvage by use of Iloprost for ergotism.

PMID- 9631898
TI  - Septal panniculitis induced by atenolol--a case report.
AB  - The authors report a case of septal panniculitis induced by atenolol in a patient
      with coronary artery disease. Several tender, erythematous, suppurated
      subcutaneous nodules appeared over the metacarpal-phalanx and interphalanx joints
      of both hands. Hematology indicated a transient inflammatory immunomediated
      disorder, with an increase of cytotoxic suppressor lymphocytes and presence of
      antinuclear antibodies. The dramatic inflammatory involvement of the subcutaneous
      connective tissue could have eventually progressed toward fibrosis, if atenolol
      had not been withdrawn. This raises the possibility that retroperitoneal
      fibrosis, a recognized adverse effect of beta blockers, may just represent the
      terminal phase of undetected connective tissue inflammation occurring in
      districts not easily explorable before overt manifestations of the disease. Since
      retroperitoneal fibrosis has already been associated with migratory panniculitis
      and described as mesenteric panniculitis, it is tempting to speculate that these
      manifestations originate from the same mechanisms.

PMID- 9631899
TI  - Implications of community lack of knowledge of colorectal cancer.

PMID- 9631900
TI  - Training in colonoscopy: a personal view.

PMID- 9631901
TI  - Laparoscopic colectomy for cancer: a review.
AB  - BACKGROUND: The success of laparoscopic cholecystectomy in providing patient
      benefits in the immediate postoperative period has led to laparoscopic techniques
      being used for many other intra-abdominal procedures. Colorectal resection for
      malignancy is one of the more contentious applications of this new technology,
      because the postoperative benefits are more subtle and the long-term onco logical
      results are as yet unknown. METHODS: A review of the English-language literature
      was undertaken in order to collate and analyse all published series where 20 or
      more laparoscopic colectomies were performed. and where the indication for
      resection in the majority of cases was adenocarcinoma of the colon. RESULTS:
      Laparoscopic colectomy for cancer can be performed safely by experienced
      surgeons, although there is a considerable learning curve for the procedure. The
      expected benefits of minimal access surgery are provided by laparoscopic
      colectomy, although to a lesser extent than that seen with other procedures. The
      oncological safety of the procedure is as yet unproven. It is clear that an
      equivalent resection can be performed, but not whether this translates to an
      equivalent recurrence and survival rate. Reports of isolated port site
      recurrences are of concern. CONCLUSIONS: Early results of laparoscopic colectomy
      for cancer are encouraging, although the fate of this procedure rests with the
      analysis of the large multicentre prospective randomized trials currently under
      way, particularly with regard to the long-term recurrence and survival rates.

PMID- 9631902
TI  - Community (mis)understanding of colorectal cancer treatment.
AB  - BACKGROUND: A study was undertaken to assess community understanding of
      colorectal cancer symptoms and colorectal cancer treatment. METHODS: A computer
      assisted telephone survey was undertaken to interview 1000 men and women aged 40
      60 years. RESULTS: Overall there was a considerable lack of information in the
      community about colorectal cancer symptoms and treatment. Men were less
      knowledgeable than women, and 28% of men were unable to name any symptoms of
      bowel cancer. Although surgery was mentioned by 53% of the sample, a third could
      not name any treatments. Most responses to questions about the effects of
      treatment related to chemotherapy-related disturbances and the possibility of
      having a colostomy bag postoperatively. CONCLUSIONS: There is inaccurate
      information in the community about colorectal cancer symptoms and treatment. This
      may inhibit involvement in screening programmes or delay presentation for
      therapy, as a result of undue concern about the prospects of treatment.

PMID- 9631903
TI  - Diagnostic failure in colonoscopies for malignant disease.
AB  - BACKGROUND: While colonoscopy has become established as more accurate than double
      contrast barium enema for detecting colonic polyps and cancers, as well as
      offering the opportunity for therapy, there are occasional instances where
      colonoscopy is misleading. The present study is to determine what problems occur,
      with a view to finding a solution. METHODS: The records of the Colorectal Project
      at the Princess Alexandra Hospital indicate retrospectively that 346 patients
      have been correctly diagnosed with cancer of the colon and rectum by colonoscopy
      in the 5 years up to October 1996. During the same time eight patients (2.3%)
      were recorded at the same hospital as being misdiagnosed by colonoscopy, the
      lesion being either missed completely or misplaced. RESULTS: In five of these
      patients there was failure to recognize that the whole colon had not been
      examined endoscopically, thereby missing a more proximal lesion. In two patients
      the lesion was missed although the entire colon was examined. In one patient the
      lesion was discovered but inaccurately sited. Six of these mistakes would have
      been obviated by the routine use of fluoroscopy to confirm the totality of the
      colonoscopy and to site any lesions found. The other two cases occurred because
      of failure to remember that colonic examination during withdrawal should be
      performed meticulously back as far as the anal canal. Failure to diagnose a colon
      cancer on the initial colonoscopy led to an average delay of 6 months for
      definitive care. CONCLUSIONS: It is recommended that fluoroscopy be used
      routinely during colonoscopy to site accurately any lesions found, and to confirm
      the completeness of insertion if reliable landmarks, including terminal ileum,
      are not clearly identified.

PMID- 9631904
TI  - Randomized controlled trial comparing same-day discharge with hospital stay
      following haemorrhoidectomy.
AB  - BACKGROUND: A randomized controlled trial was conducted to compare traditional
      hospital stay haemorrhoidectomy (STAY) with same-day discharge haemorrhoidectomy
      (DAY) with regard to costs, clinical outcome and patient satisfaction. METHODS: A
      total of 54 consecutive patients were randomized to either STAY or DAY groups. A
      standardized excision of three piles was performed and the wounds were left open.
      The DAY patients went home on the same day but the STAY patients remained in
      hospital until their bowels had opened. A linear analogue pain score and patient
      satisfaction questionnaire were administered. During a mean follow-up of 60.5
      (standard error of mean = 1.2) weeks, the complications and the total medical
      costs were recorded RESULTS: There were no differences in the age and sex
      distributions in both groups (STAY: 11 men, 16 women; mean age 40.6 (+/- 1.8)
      years; DAY: 10 men, 17 women; mean age 40.6 (+/- 1.9) years). Despite accounting
      for any readmissions, the DAY patients accumulated shorter total hospitalization
      stays (P < 0.001) and incurred less total medical costs (P = 0.04). The pain
      scores, analgesia requirements, postoperative complications, patient satisfaction
      and time taken off work were not different between the two groups. However, more
      patients in both groups preferred to stay after surgery if they should need
      another haemorrhoidectomy. CONCLUSIONS: Haemorrhoidectomy (with excision of three
      piles) can be safely performed as a day procedure, with reduced hospitalization
      and medical costs.

PMID- 9631905
TI  - Appendicitis in HIV-positive patients.
AB  - BACKGROUND: The aim of the present study was to review the experience of
      appendicitis in human immunodeficiency virus (HIV)-positive patients. METHODS: A
      retrospective analysis of all HIV-positive patients operated on for suspected
      acute appendicitis during a 10-year period at St Vincent's Hospital was
      performed. These patients were compared to a group of 60 age- and sex-matched
      patients with no HIV risk factors who were operated on during the same time
      period. RESULTS: On presentation the clinical findings were similar in both
      groups, with two notable exceptions. No HIV-positive patient had an elevated
      white cell count. The present study demonstrated a significant delay in
      presentation of the HIV-positive group to the Emergency Department, possibly
      explaining the higher appendiceal perforation rate in this group. There were no
      cases of HIV-related diseases mimicking acute appendicitis. There was no
      mortality, and morbidity was higher in the seropositive group. CONCLUSIONS: HIV
      positive patients with a history suggestive of acute appendicitis should not be
      treated differently from the normal population. Morbidity and mortality can be
      minimized by prompt surgical treatment.

PMID- 9631906
TI  - Bacillus Calmette-Guerin (BCG) immunotherapy for bladder cancer: review of
      complications and their treatment.
AB  - BACKGROUND: Intravesical bacillus Calmette-Guerin (BCG) is widely used in the
      management of bladder cancer but because it is a living organism, local and
      disseminated infection may result. METHODS: A prospective assessment of
      complications of this therapy in 200 patients in Queensland was performed. A
      review of management of complications of intravesical BCG was also carried out.
      RESULTS: Major side effects were rare. Cystitis was the most common side effect,
      being seen to some degree in all patients, although only forcing cessation of BCG
      therapy in two patients. Two patients developed persistent cystitis necessitating
      institution of isoniazid and rifampicin. Two patients had culture-proven bladder
      infection that presented several months after the BCG treatment. These patients
      also responded to two-drug antituberculous therapy. While low-grade fever is very
      common with this therapy, seven patients (3.5%) had fevers of > 39 degrees C
      within 48 h of receiving BCG. Fevers may be an indication of severe disseminated
      mycobacterial infection, which has a high mortality, so it needs to be treated
      aggressively. Alternatively bacterial sepsis with gram-negative bacterial
      pathogens or a hypersensitivity reaction to BCG may cause this degree of fever,
      and cannot be rapidly distinguished from fulminant mycobacterial infection. One
      patient in the present series developed pneumonia attributed to mycobacterial
      dissemination. CONCLUSIONS: The key to appropriate management of complications of
      BCG therapy is awareness of their possibility, even months or years after the
      therapy has been given. Appropriate empirical therapy in acute situations and
      mycobacterial culture in chronic situations can then be performed.

PMID- 9631907
TI  - Pre-operative core biopsy of soft-tissue tumours facilitates their surgical
      management.
AB  - BACKGROUND: Soft-tissue sarcomas are rare, and clinical differentiation of benign
      tumours from sarcomas is sometimes impossible. Further, the diagnosis of soft
      tissue sarcomas may be unsuspected pre-operatively, and the presenting mass
      enucleated. While enucleation (excisional biopsy) is acceptable for benign
      lesions, it is inappropriate for sarcomas, because the opportunity for the most
      effective management resulting in both adequate local control and functional limb
      salvage surgery is compromised. A high rate of wound complications following open
      incisional biopsy may also compromise local treatment. Inappropriate siting of
      the incision for both incisional and excisional biopsies may adversely affect
      subsequent surgery and radiotherapy. METHODS: We therefore assessed the accuracy
      of core biopsy in the diagnosis of soft-tissue tumours, and planning of
      definitive surgery. All patients with primary soft-tissue tumours managed by two
      surgeons with a special interest in soft-tissue sarcomas since 1991 were
      reviewed. More than half (53%) were referred from other specialists. RESULTS: Of
      45 cases, 37 (82%) were referred with the tumour intact, and of these 31 (84%)
      underwent core biopsy. The overall accuracy of core biopsy was 84%. The
      sensitivity was 94%, with 100% specificity. In most patients this allowed
      planning of definitive one-stage surgery (P < 0.005). Of the remaining five non
      diagnostic cores, four were benign and one was a non-specific malignancy.
      CONCLUSIONS: Core biopsy has a high degree of accuracy in the diagnosis of soft
      tissue tumours, particularly malignant lesions, and is not misleading. Core
      biopsy avoids the complications of open biopsy, and enables planning of one-stage
      surgery when used in combination with appropriate imaging.

PMID- 9631908
TI  - Craniofacial resection of anterior skull base tumours: factors contributing to
      success.
AB  - BACKGROUND: A case series of 20 consecutive patients followed for a minimum of 54
      months following craniofacial resection of anterior skull base tumours is
      presented, with the aim of identifying complications and factors influencing
      survival. METHODS: A retrospective review of a case series of 20 consecutive
      patients was carried out. RESULTS: Dural invasion was significantly correlated
      with poorer survival. There was also a tendency for tumour grade and positive
      resection margins to be associated with poorer outcome. Most local recurrences
      occurred within 6 months of surgery, with the exception of adenocarcinoma of the
      ethmoids, in which recurrence occurred up to 36 months postoperatively. A variety
      of complications were encountered, with a marked decrease in serious
      complications from midway through the series. CONCLUSIONS: The change in pattern
      of complications may be indicative of a learning curve, or the discontinuation of
      the use of lumbar drainage.

PMID- 9631909
TI  - Clinical management and treatment outcomes of Merkel cell carcinoma.
AB  - BACKGROUND: Merkel cell carcinoma (MCC), first described in 1972, is an uncommon,
      highly malignant tumour of skin. Its aetiology is unknown although the tumour
      occurs most frequently in sun-exposed sites. This skin cancer is characterized by
      a high incidence of metastases, local and regional recurrence and has a high
      mortality. Few survival data beyond 3 years are available. Treatment strategies
      include wide local excision of the primary and lymph node dissection, as
      indicated together with adjuvant radiotherapy. The tumour has also been shown to
      be chemosensitive. Definitive treatment is inconclusive due to the relative
      rarity of this malignancy. METHODS: A retrospective study was undertaken between
      the years 1985 and 1996 of 33 patients with MCC at Concord Repatriation General
      Hospital (CRGH). Demographic details were noted, together with the site and
      appearance of the primary lesion and the sites and date of metastases. The
      response and outcome to various modalities of treatment were documented. RESULTS:
      There were 27 men and six women with an average age of 80 years (range: 60-86
      years). The primary lesion in the present series most often resembled a basal
      cell carcinoma (BCC), with 53% occurring in the head and neck region. Twenty
      seven patients (82%) developed metastatic disease, with an average interval of
      13.4 months between diagnosis of the primary lesion and the development of
      metastases. The incidence of locoregional recurrence in the present series was
      42%. Radiation combined with surgery achieved locoregional control in 15 of 19
      patients with primary, regional or recurrent locoregional disease. Fourteen
      patients died of MCC and five others from unrelated causes. The 14 survivors have
      a mean survival of 54 months with six patients surviving more than 5 years.
      CONCLUSIONS: Local excision together with regional lymph node clearance as
      indicated, combined with adjuvant radiation treatment was associated with an
      improved survival. The role of chemotherapy remains unclear.

PMID- 9631910
TI  - Extracranial repair of cerebrospinal fluid rhinorrhoea.
AB  - BACKGROUND: Extracranial techniques, which have none of the inherent morbidity
      associated with intracranial techniques, can successfully repair rhinological
      cerebrospinal fluid (CSF) fistulas. METHODS: A series of five consecutive adult
      patients with persistent rhinological CSF fistulas were reviewed retrospectively.
      RESULTS: The success rate for initial closure was 60%. On the second operation
      both failures were successfully repaired. CONCLUSIONS: The external approach is a
      safe, successful, alternative approach for the surgical repair of rhinological
      CSF fistulas.

PMID- 9631911
TI  - Tumour cell wound distribution after colectomy in a porcine model.
AB  - BACKGROUND: Concerns over tumour implants have impeded the adoption of
      laparoscopic surgery for cancer. Explanations assume an increased number of
      malignant cells present in trocar wound sites. The following are tested in the
      present paper: (i) that the magnitude of wound contamination following surgery is
      related to the location of the tumour cells; and (ii) the surgical approach.
      METHODS: We have used a porcine sigmoid colectomy model to compare the number of
      tumour cells on laparoscopic wounds after resections in the presence of
      intraluminal, intramural and intraperitoneal 51Cr-labelled, fixed HeLa tracer
      cells. Open colectomies were also performed in the presence of intraperitoneal
      tracer cells and their numbers on laparotomy wound surfaces were determined by
      gamma counting. RESULTS: With intraperitoneal cells, laparotomies had 1087 (+/-
      106) tracer cells per mm (n = 4) while trocar wounds had 103 (+/- 54) cells per
      mm (n = 10) (P > 0.05). Resection of intramural tumours resulted in lower trocar
      wound contamination (0.9 +/- 0.6 cells/mm, n = 3). Resection of colon including
      intraluminal tracer cells resulted in 2.9 +/- 2.1 cells/mm on trocar wounds (n =
      3). CONCLUSIONS: More tumour cells were deposited on open than laparoscopic
      trocar wound surfaces. Also, the risk of wound implantation is less with
      intraluminal or intramural tumours than with intraperitoneal cells (P > 0.05).

PMID- 9631912
TI  - Construction of continent catheterizable urinary conduit from an isolated segment
      of colon.
AB  - BACKGROUND: Continent urinary diversion may be necessary in a range of urological
      abnormalities. In circumstances where the standard techniques are not possible,
      alternative innovative techniques may be used. METHODS: In a female patient with
      bladder exstrophy, a continent diversion was recommended. The appendix was not
      available, the ureters were not suitable and a continent stoma was fashioned from
      an isolated segment of colon. RESULTS: The stoma proved to be continent, although
      it was somewhat stenotic. However, clean intermittent catheterization maintained
      its patency. CONCLUSIONS: A continent catheterizable stoma may be constructed
      from a segment of colon. The technique may be considered when other well
      recognized methods are not feasible.

PMID- 9631913
TI  - Management of invasive penile cancer by synchronous penile lengthening and
      radical tumour excision to avoid perineal urethrostomy.
AB  - BACKGROUND: Adequate excision of invasive penile carcinoma often results in a
      penile stump of inadequate length to control the urinary stream. A simple
      technique to lengthen the stump and avoid urethrostomy is described here.
      METHODS: Additional corporal length is gained by dividing the dorsal suspensory
      ligaments through a transverse lower abdominal skin incision. Skin length is
      gained by vertical closure of this incision. RESULTS: This technique has been
      successful in two cases where the stump length after partial penectomy was
      borderline. Each patient has a functional stump with satisfactory cosmesis.
      CONCLUSIONS: In selected cases this technique may avert the need for perineal
      urethrostomy after adequate excision of a penile cancer.

PMID- 9631914
TI  - Spontaneous retroperitoneal haemorrhage: a general surgeon's perspective.

PMID- 9631915
TI  - Spontaneous oesophageal perforation with simultaneous perforated duodenal ulcer.

PMID- 9631916
TI  - Renal autotransplantation for the management of complex ureteric defects.

PMID- 9631917
TI  - Traumatic duodenal perforations in children: child abuse a frequent cause.

PMID- 9631918
TI  - Genetic polymorphism of cytochrome P450s, CYP2C19, and CYP2C9 in a Japanese
      population.
AB  - Genotypings of two mutations (*2 and *3) in CYP2C19 and the amino acid variants
      (Arg144/Cys, Tyr358/Cys, Ile359/Leu, and Gly417/Asp) in CYP2C9 were carried out
      in 140 unrelated Japanese subjects. Thirty-three subjects (23.6%) were
      genotypically identified as poor metabolizers of CYP2C19, and the allele
      frequencies of the CYP2C19*2 and CYP2C19*3 were 0.35 and 0.11, respectively. The
      authors' findings are in agreement with the 18% to 23% prevalence of poor
      metabolizers in the Japanese populations previously phenotyped. In CYP2C9, all
      subjects were homozygous (CYP2C9*1) for Arg144, Tyr358, Ile359, and Gly417,
      except for five subjects (3.6%) who were heterozygous for the Leu359 (CYP2C9*3).
      The frequencies of Arg144, Tyr358, Ile359, Leu359, and Gly417 variants were 1.0,
      1.0, 0.982, 0.018, and 1.0, respectively. The low frequency of the Cys144 allele
      (CYP2C9*2) in the Japanese population is different from the frequency recently
      found in British subjects (allele frequency, 0.125 to 0.192). The results suggest
      that the known interindividual variations in the CYP2C9 sequence among Japanese
      subjects is small, and that Ile359/Leu is one possible site showing interracial
      polymorphism.

PMID- 9631919
TI  - An audit of therapeutic drug monitoring service provision by laboratories
      participating in an external quality assessment scheme.
AB  - Therapeutic drug monitoring services were investigated in a questionnaire sent to
      all subscribers to the United Kingdom National External Quality Assessment Scheme
      for Therapeutic Drug Assays. Questions were posed on assay availability and use,
      target ranges, and reporting procedures for digoxin, lithium, phenytoin,
      phenobarbitone, carbamazepine, theophylline, and valproic acid. One hundred fifty
      seven laboratories replied and, except for lithium, 45% reported in mass units,
      34% in molar units, and 22% a mixture of mass and molar units. Target ranges for
      lithium, digoxin, carbamazepine, and phenobarbitone were highly variable but
      ranges for phenytoin, theophylline, and valproic acid were more consistent.
      Immunoassay was the most popular methodology although high-performance liquid
      chromatography was commonly used for anticonvulsants. Paper copies of results
      were provided by 93% of laboratories, 40% reported by telephone, 12% by fax, and
      28% by computer. Additional data, mainly dose, time of last dose, and duration of
      therapy were requested by 55% to 67% of laboratories. Grades of staff authorizing
      results ranged from nurses to senior consultants, and collaboration with
      pharmacists occurred in 26% of laboratories. Most laboratories provided a daily
      analytical service and 73% offered a 24-hour emergency service. This audit
      unexpectedly identified use of a wide range of target concentrations,
      particularly for digoxin and lithium.

PMID- 9631920
TI  - Clinical relevance of therapeutic drug monitoring of digoxin and gentamicin in
      the saliva of children.
AB  - Digoxin and gentamicin are widely used in pediatric medicine, and therapeutic
      monitoring is mandatory because of their narrow margin of safety and wide
      interpatient and intrapatient pharmacokinetic variabilities. Saliva sampling may
      be of potential interest, especially in children, in whom blood sampling is often
      difficult. In 11 children treated with digoxin for various cardiac conditions,
      and in 24 children treated with gentamicin (14 patients were administered
      gentamicin three times a day, and 10 once-daily), drugs levels were measured in
      plasma and saliva. There was no correlation between plasma total or free digoxin
      concentrations and saliva levels, precluding the clinical use of the saliva test
      for digoxin. No correlation was found between plasma gentamicin concentrations
      and saliva levels when the drug was administered three times a day; however, good
      correlation was found when the drug was administered once-daily (r2 = 0.89, p <
      0.0001). Saliva may be used as a noninvasive method of measuring gentamicin serum
      concentrations to guide dosage adjustments in patients administered the drug once
      daily.

PMID- 9631921
TI  - Therapeutic drug monitoring of alprazolam in adolescents with asthma.
AB  - Children and adolescents with severe asthma frequently experience anxiety or
      depression with anxiety, which can undermine their response to treatment. In
      addition, these patients often receive theophylline and a variety of adrenergic
      stimulants, which can exacerbate or worsen anxiety. Such children occasionally
      are candidates for treatment with anxiolytic therapy. There is a paucity of drug
      disposition data in adolescents for benzodiazepines, the most frequently used
      antianxiety drugs. The authors monitored the steady state alprazolam plasma
      concentration in six children with severe asthma who were administered standard
      doses of alprazolam. In one patient administered concurrent therapy with
      troleandomycin, a recognized cytochrome 3A4 inhibitor, alprazolam plasma
      concentration was markedly elevated. Overall, the disposition data of alprazolam
      was consistent with data previously reported in adults. Alprazolam appeared to be
      safe and effective for use in adolescents with asthma.

PMID- 9631922
TI  - Therapeutic drug monitoring of vancomycin in a morbidly obese patient.
AB  - The authors describe the therapeutic drug monitoring of vancomycin in a man who
      is morbidly obese. Because serum vancomycin concentration (SVC) monitoring
      continues to be deemphasized, nomogram use will likely increase. However,
      vancomycin dosing nomograms have not been studied in patients who are morbidly
      obese. Furthermore, in nomograms that incorporate body weight, it is unclear
      whether ideal or total body weight (IBW and TBW, respectively) should be used to
      dose the morbidly obese. Therefore, the authors retrospectively evaluated four
      nomograms (Moellering, Matzke, Lake-Peterson, and Rodvold) and an individualized
      method in the simulated vancomycin dosing of their patient. Total body weight was
      more accurate than IBW in selecting a vancomycin dose when using the
      individualized method and in all nomograms except the Matzke nomogram. The
      Rodvold nomogram and the individualized method yielded the most appropriate
      doses. All nomograms suggested dosing intervals that were unacceptably short; the
      individualized method suggested an appropriately longer interval. Thus, if
      nomograms or the individualized method are used to empirically dose vancomycin,
      TBW--not IBW--should be used. Because these nomograms yielded inappropriately
      short dosing intervals in the patient, it is likely that patients who are
      morbidly obese represent a unique population in which at least one set of SVCs
      are necessary to select an appropriate dosing regimen.

PMID- 9631923
TI  - Therapeutic monitoring of tacrolimus (FK506) with the first- and second
      generation microparticle enzyme immunoassays: performance and results in four
      patient populations.
AB  - The performance of the first- and second-generation microparticle enzyme
      immunoassays for tacrolimus (Tacrolimus I and Tacrolimus II, respectively) was
      compared during 8 months routine drug monitoring. The minimum detection limit of
      the Tacrolimus II assay was lower: 1.4 versus 4.0 microg tacrolimus/l. There was
      also no overlap between results using 10 samples containing 0 and 1 microg
      tacrolimus/l in the Tacrolimus II assay (p < 0.001), with a corresponding
      significant difference achieved for the Tacrolimus I assay only at 0 and 4
      microg/l. For control specimens, within-assay precision was superior for
      Tacrolimus II at 5 microg/l (7.3% vs. 31.5%), similar at 10 and 15 microg/l (6.3%
      versus 6.6% and 4.4% vs. 4.6%, respectively) but worse than Tacrolimus I at 25
      microg/l (8.0% vs. 4.0%). Using three pools of blood samples from recipients of
      liver transplants (containing approximately 4, 10, and 20 microg tacrolimus/l)
      interassay precision (n > 20) was 14.2%, 10.4%, and 8.0% for Tacrolimus II and
      42.4%, 13.8%, and 7.1%, for Tacrolimus I. The analytical times and stability of
      the calibration curves were similar for the two assays. Tacrolimus I and
      Tacrolimus II results were closely correlated using patients' blood samples (r
      approximately equal to 0.8 in 249 adult and 168 pediatric liver transplant
      samples, 161 renal transplant samples, and 61 samples from patients with
      autoimmune diseases). However, Tacrolimus II assay results were consistently
      lower (by a mean of 1.02 to 2.05 microg/l). The authors conclude that the
      Tacrolimus II assay retains the speed, accuracy, and precision of its predecessor
      and demonstrates an improved sensitivity, which should facilitate monitoring at
      less than 5 microg tacrolimus/l.

PMID- 9631924
TI  - Cyclosporine monitoring in patients with renal transplants: two- or three-point
      methods that estimate area under the curve are superior to trough levels in
      predicting drug exposure.
AB  - The recent introduction of a cyclosporine microemulsion demonstrating less
      pharmacokinetic variability than the conventional formulation offers the
      potential for accurately and precisely predicting area under the curve (AUC) with
      a limited-sampling monitoring strategy. This was studied based on the
      pharmacokinetic profiles from 55 stable patients with renal transplants who were
      observed on two occasions at steady state on both formulations. Multiple linear
      regression analyses were performed on a training dataset from 27 patients, in
      which combinations of cyclosporine concentrations drawn from 0 to 4 hours
      postdose were regressed against the full AUC over the dosing interval. Predictor
      regression equations used concentration combinations ranging from one-point
      (concentrations at 0, 1, 2, 3, or 4 hours) through five-points (all five
      concentrations 0 to 4 hours). The predictive performance of these equations was
      then assessed in the training group with data from a subsequent profiling
      occasion and in the remaining 28 patients who constituted an independent test
      group. Prediction bias (mean prediction error) and prediction precision (absolute
      prediction error) were quantified and compared between formulations. Correlations
      between predicted and actual AUC were consistently stronger for the
      microemulsion, suggesting the possibility of more accurate and precise
      predictions of exposure than from the conventional formulation. For both
      formulations, the one-point predictors rendered the lowest prediction precision,
      and predictive performance improved considerably when multiple-point predictors
      were used. Significantly higher precision and lower variability were observed
      with the microemulsion for most predictors in the both training and test groups.
      For the microemulsion, two-point (C0 + C1 or C0 + C2) and three-point (C0 + C1 +
      C2) predictors yielded relatively unbiased and precise exposure predictions,
      inasmuch as mean absolute prediction error was less than 10% and 5%,
      respectively. Hence, a two- or three-point method may provide a clinically
      important improvement over the use of trough levels in monitoring cyclosporine
      therapy in patients with renal transplants.

PMID- 9631925
TI  - NONMEM population pharmacokinetic modeling of orally administered cyclosporine
      from routine drug monitoring data after heart transplantation.
AB  - The population pharmacokinetics of cyclosporine (CsA) in adult recipients of
      cardiac transplants were determined from sparse, retrospective drug monitoring
      data accumulated for at least 3 months after surgery. All were receiving oral CsA
      twice daily, and morning trough levels in whole-blood were measured by high
      performance liquid chromatography. Additional data included height, weight,
      gender, age, ethnicity, hematocrit, total bilirubin, and concurrent drug use.
      Population modeling was performed using NONMEM on 36 randomly selected patients,
      assuming a one-compartment model with first-order absorption and elimination.
      Improved fits were obtained by incorporating the following expression in the
      model to adjust oral bioavailability as a function of postoperative day (POD): F
      = 0.2 + 10 x ABS (POD - 7)/([POD + 10] x 60). Interpatient variability (CV%) in
      clearance (CL) was 20.2%. There was a mean bias of 8.5% at the average CsA
      concentration of 250 ng/ml when the predictive performance was assessed
      statistically in a reserved subset of 33 patients who received cardiac
      transplants. For the entire population (n = 69 patients), the average CsA CL and
      terminal half-life (T1/2) were, respectively: CL (l/h) = 0.256 x weight (kg);
      T1/2 = 11.0 hours, or CL (l/h) = 0.184 x weight (kg); T1/2 = 14.7 hours, if there
      was concomitant diltiazem administration. These results compared favorably with
      those reported elsewhere for studies of postcardiac transplant kinetics using the
      traditional multiple blood sampling approach.

PMID- 9631926
TI  - A specific method for the measurement of cyclosporin A in human whole blood by
      liquid chromatography-tandem mass spectrometry.
AB  - Therapeutic monitoring of the immunosuppressant cyclosporin A (CsA) is routinely
      performed by immunoassays to make individual dosage adjustments for patients
      after organ transplantation. High-performance liquid chromatography with
      ultraviolet detection (HPLC-UV) has been used as the reference method. However,
      HPLC-UV methods frequently suffer from chromatographic interferences that affect
      accuracy and reproducibility. A sensitive, specific HPLC-tandem mass spectrometry
      (HPLC/MS/MS) method for the quantitation of CsA has been developed. One hundred
      microliters CsA whole blood sample containing cyclosporin C (CsC) as the internal
      standard was extracted with ethyl ether. High-performance liquid chromatography
      separation was accomplished on an RP-C18 narrow-bore column at 50 degrees C with
      a linear gradient elution followed by on-line ion-spray ionization MS/MS
      analysis. The standard curve was established in the range of 10 to 1000 microg/l
      (r = 0.9989, n = 8). Limits of detection and quantitation were 1 microg/l and 5
      microg/l, respectively. Imprecision was <4% across three control levels.
      Cyclosporine A recovery averaged 88%. Six metabolites: AM1, AM9, AM4N, Am1c,
      AM1a, and AM19 were identified with this method. AM1, AM9, and AM1c were further
      differentiated with a modification to the MS/MS conditions. This method was used
      in a comparison study with an HPLC-UV method: HPLC = 1.055 LC/MS/MS + 7.05
      (microg/l), (Sy/x = 25.7), r2 = 0.982. With its high degree of sensitivity and
      specificity, this LC/MS/MS method offers a valuable reference method for
      immunoassay evaluation and a tool for metabolite investigation.

PMID- 9631927
TI  - Indirect estimation of the unbound fraction of cyclosporine in plasma.
AB  - The unbound fraction (fU) of cyclosporine in plasma is approximately 0.02. The
      measurement of cyclosporine fU requires a laborious equilibrium dialysis
      procedure, which is not practical in a clinical setting. A mathematical model was
      developed to estimate cyclosporine fU from concentrations of serum lipoproteins,
      the major binding proteins for cyclosporine. Values of fU were determined ex vivo
      in 126 plasma samples obtained from 58 recipients of heart and lung transplants,
      using equilibrium dialysis. Concentrations of serum lipids, measured using
      standard enzymatic techniques, were used as concentration markers for serum
      lipoproteins. Patients were randomly assigned to either of two equal-sized
      groups. One group (subgroup 1) was used to evaluate the parameters of the model,
      and the other group (subgroup 2) was used to examine its predictive performance.
      The parameters were estimated using least squares non-linear regression. A model
      incorporating concentrations of serum HDL- and LDL-cholesterol, serum albumin,
      and time after transplantation gave the best fit. For subgroup 2, mean prediction
      error (ME), a measure of bias, and root mean squared error (RMSE) and median
      absolute error (MAE), measures of precision, and their 95% confidence intervals
      were estimated. For the best fit model, ME was 0.07 x 10(-2) (-0.065 x 10(-2) -
      0.1 x 10(-2)), indicating that the model provided an unbiased estimate of the
      value of cyclosporine fU. Root mean squared error and MAE were 0.536 x 10(-2)
      (0.398 x 10(-2) - 0.645 x 10(-2)) and 0.27 x 10(-2) (0.226 x 10(-2) - 0.409 x 10(
      2)), respectively. Prediction error was normally distributed; approximately 30%
      of the prediction errors were <10% and <5% of prediction errors were >50%. This
      model has shown a reasonable predictive performance in the patients with cardiac
      transplants studied; however, its predictive performance will need to be
      validated in a larger number of recipients of transplants of various types.

PMID- 9631928
TI  - Postmortem changes in blood concentrations of phenytoin and carbamazepine: an
      experimental study.
AB  - Observations of low postmortem blood concentrations of antiepileptic drugs in
      cases of sudden unexpected death in epilepsy (SUDEP) have led to the assumption
      that noncompliance may play a role in SUDEP. However, the reliability of
      postmortem drug levels has been questioned. The purpose of this study was to
      analyze possible postmortem changes in blood concentrations of carbamazepine
      (CBZ) and phenytoin (PHT). New Zealand white rabbits were fed with PHT or CBZ
      until assumed steady state. A blood sample was then drawn for determination of
      serum and whole blood concentrations of CBZ and PHT, after which the rabbits were
      killed and stored at 6 degrees C. A further blood sample for drug analysis was
      obtained 72 hours after death. Antemortem serum concentrations of CBZ were not
      significantly different from whole blood concentration 72 hours after death. In
      contrast, antemortem whole blood concentrations of PHT were only 65% of the
      corresponding serum concentrations, and postmortem PHT blood levels were even
      lower, being 35% of antemortem serum concentrations. In conclusion, blood
      concentrations of CBZ seem to be stable during 72 hours after death under these
      experimental conditions. However, postmortem PHT concentrations should be
      interpreted with caution and low postmortem concentrations do not necessarily
      imply a poor compliance.

PMID- 9631929
TI  - Gas chromatography-electron ionization and chemical ionization mass spectrometric
      analysis of serum mexiletine concentration after derivatization with 2,2,2
      trichloroethyl chloroformate: a novel derivative.
AB  - Mexiletine (Mexitil) is an antiarrhythmic agent used in the treatment of
      ventricular arrhythmia. The drug has a narrow therapeutic window, and monitoring
      its serum concentration is recommended. The authors describe a gas chromatography
      mass spectrometric (GC/MS) assay of mexiletine using selected ion monitoring.
      Mexiletine was extracted from alkaline serum with dichloromethane followed by
      derivatization with 2,2,2-trichloroethyl chloroformate. The reaction was
      completed in 30 minutes at 70 degrees C. N-propylamphetamine was used as the
      internal standard. The ions monitored were m/z 58, 102, 122, 232, and 234 for
      derivatized mexiletine and m/z 56, 91, 131, 260, and 262 for the derivatized
      internal standard. The within-run precision at a serum mexiletine concentration
      of 1 mg/l was 1.7% (mean = 0.981, SD = 0.017 mg/l, n = 8) and the between-run
      precision was 3.3% (mean = 0.983, SD = 0.033 mg/l, n = 6). The assay was linear
      for serum mexiletine concentrations of 0.2 to 2.5 mg/l. The detection limit was
      0.1 mg/l. The authors observed no carry-over problem in their assay. They
      observed a good correlation between mexiletine concentrations measured by a
      reference laboratory (Associated Regional University Pathologists, Salt Lake
      City, UT, U.S.A.) and by the new GC/MS assay.

PMID- 9631930
TI  - Analysis of midazolam and metabolites in plasma by high-performance liquid
      chromatography: probe of CYP3A.
AB  - Hydroxylation of midazolam (MDZ) is mediated almost exclusively by CYP3A
      isoforms. The authors describe a high-performance liquid chromatography assay
      involving MDZ, 1'-hydroxymidazolam, and 4-hydroxymidazolam in plasma. The
      compounds were eluted on an Ultrasphere ODS, 3-microm particle size, 7.5 cm x 4.6
      mm reversed-phase column and monitored by ultraviolet absorbance at 254 nm. The
      composition of the mobile phase was 35.2% acetonitrile:4.8% methanol:60% buffer
      acetate (vol/vol/vol), 0.1 M, pH 4.7; the flow rate was 1 ml/minute. Calibration
      curves were linear (coefficients of correlation > 0.99) within the range of
      concentrations established (20 to 640 nM). Within- and between-day coefficients
      of variation were consistently better than 8%. The overall recovery was >90% and
      the lowest detectable concentration was 8 nM. This approach provides a simple,
      rapid, and sensitive assessment of MDZ and metabolites in plasma, with a very
      good accuracy and precision, which enables it as an in vivo marker of CYP3A
      activity in humans.

PMID- 9631931
TI  - Improved validated assay for the determination of proguanil and its metabolites
      in plasma, whole blood, and urine using solid-phase extraction and high
      performance liquid chromatography.
AB  - An improved and validated method is presented for the determination of proguanil,
      cycloguanil, and 4-chlorophenylbiguanide in plasma, whole blood, and urine using
      solid-phase extraction (SPE) technique and reversed-phase high-performance liquid
      chromatography (HPLC). The HPLC method uses isocratic elution with
      acetonitrile:phosphate buffer 0.1 mol/l, pH 2.6 (21.5:78.5 vol/vol) at a flow
      rate of 1.0 ml/min for the separation. The recovery of proguanil and metabolites
      ranged from 82% to 104%. The limit of determination was 20 nmol/l for proguanil
      and its metabolites in plasma and approximately 50 nmol/l for proguanil and
      metabolites in whole blood. Different stationary phases for HPLC and SPE were
      tested and the best chromatographic separation from endogenous constituents and
      other antimalarial drugs was achieved with cyanopropyl stationary phases.

PMID- 9631932
TI  - Improved cross-reactivity to alpha OH triazolam in the BMC CEDIA DAU urine
      benzodiazepine assay.
AB  - Immunoassays designed to detect use of older benzodiazepines such as oxazepam or
      diazepam often cannot detect triazolam use because of the low doses of triazolam
      administered, rapid biotransformation to metabolites with poor cross
      reactivities, and the small amount of alpha OH triazolam glucuronide excreted in
      the urine. Previous studies have demonstrated that certain immunoassays have high
      cross-reactivity to alpha OH triazolam but are unable to detect therapeutic
      triazolam use in urine. The objectives of this study were to characterize the
      immunoreactivity toward alpha OH triazolam in the reformulated cloned enzyme
      donor immunoassay (CEDIA) drug abuse urine benzodiazepine assay and to measure
      the immunoreactivity of urine specimens from subjects who were administered
      single oral doses of triazolam. Alpha OH triazolam standards were prepared in
      drug-free urine and the new CEDIA assay gave a positive result at concentrations
      from 100 to 200 ng/ml, which indicates an eight-fold improvement in CEDIA cross
      reactivity to alpha OH triazolam standards in the reformulated CEDIA assay. With
      a 200 ng/ml cut-off, 4/30 of the urine specimens screened positive for
      benzodiazepines without enzymatic hydrolysis and 6/30 after enzymatic hydrolysis.
      When using an in-house 100 ng/ml nitrazepam cut-off calibrator, 10/30 urine
      specimens were positive in the reformulated CEDIA assay without hydrolysis and
      22/30 were positive with enzymatic hydrolysis before screening.

PMID- 9631933
TI  - Concurrent high-performance liquid chromatographic measurement of loxapine and
      amoxapine and of their hydroxylated metabolites in plasma.
AB  - The dibenzoxazepine neuroleptic loxapine, its N-demethylated metabolite
      amoxapine, and their 7- and 8-hydroxymetabolites were measured simultaneously in
      plasma by reversed-phase high-performance chromatographic method. An original
      liquid-liquid extraction procedure was performed, consisting in coextraction of
      the substances together with a water-miscible solvent (acetonitrile) by a non
      water-miscible solvent (toluene). The substances were separated on a 5-microm CN
      25-cm column, and eluted with a mobile phase consisting of acetonitrile-acetic
      acid 0.5 N (30:70) and hexylamine (0.05%). They were detected by ultraviolet
      spectrophotometry at 310 nm. Clozapine was used as internal standard. Linearity
      was demonstrated in the range of 10 to 250 microg/l, and detection limits were
      found to be 3.5 to 6.3 microg/l according to the substance. Within-day
      repeatability ranged from 2.7% to 6.5%, and between-day reproducibility ranged
      from 0.9% to 20.2%. The extraction procedure provided a mean absolute recovery of
      51.1% (range, 40.7% to 58.6%) with a mean coefficient of variation of 4.2%. This
      technique was applied to the concurrent determination of plasma concentrations of
      the compounds in 10 patients administered loxapine 75 to 600 mg daily. Steady
      state plasma levels of loxapine were significantly correlated with oral doses (n
      = 10, r = 0.858, p < 0.002). In conclusion, the method proved to be a convenient
      and reproducible procedure allowing the simultaneous measurement of loxapine,
      amoxapine, and their metabolites in patients.

PMID- 9631934
TI  - Quantitative determination of tricyclic antidepressants and their metabolites in
      plasma by solid-phase extraction (Bond-Elut TCA) and separation by capillary gas
      chromatography with nitrogen-phosphorous detection.
AB  - An analytical method for the simultaneous determination of amitriptyline,
      nortriptyline, imipramine, desipramine, clomipramine, and desmethylclomipramine
      in human plasma using promazine as internal standard is described. The method is
      based on a solid-phase extraction procedure using the Bond-Elut TCA columns
      followed by separation and detection using capillary gas chromatography with a
      specific nitrogen phosphorous detector (GC/NPD). Using the new extraction
      procedure, the problem of adsorption losses was overcome, and good recoveries
      were achieved for all compounds tested (>87%). Furthermore, clean extracts free
      of chromatographic interferences were obtained. Complete separation of
      underivatized, tricyclic antidepressant compounds was achieved in <11 minutes
      with reliable chromatographic performance. The limits of detection ranged from
      1.2 to 5.8 microg/l. Calibration curves, showing good linearity, were prepared
      covering the therapeutic concentrations range expected (20 to 500 microg/l). The
      interassay precision values (RSD) ranged from 4.5% to 9.8%. It is concluded that
      extraction of amitriptyline, nortriptyline, imipramine, desipramine,
      clomipramine, and desmethylclomipramine, with Bond Elut TCA solid-phase columns
      followed by their detection using GC/NPD provides a sensitive and reproducible
      method that can be easily automated for immediate and routine analysis of
      clinical samples.

PMID- 9631935
TI  - Comparison of microparticle enzyme and fluorescence polarization immunoassays in
      pediatric patients not receiving digoxin.
AB  - Previously, investigators have measured endogenous digoxin-like immunoreactive
      substances (DLIS) in pediatric patients. Digoxin-like immunoreactive substances
      may cross-react with digoxin assays to produce false-positive digoxin
      concentrations; hence, the validity of digoxin concentrations in pediatric
      patients is questionable. The authors compared the presence and magnitude of
      apparent DLIS using the microparticle enzyme immunoassay (MEIA) AxSYM Digoxin II
      and the fluorescence polarization immunoassay (FPIA) TDx Digoxin II, in the serum
      of 80 pediatric patients who were hospitalized with normal serum creatinine but
      had not been administered digoxin. Patients ranged in age from 1 day to 16 years
      (mean age, 4.96 +/- 5.17 years). Serum creatinine and total bilirubin were 0.5 +/
      0.18 mg/dl and 1.3 +/- 0.17 mg/dl, respectively. Forty-eight percent of MEIA
      samples and 79% of FPIA samples had measurable DLIS values. Digoxin-like
      immunoreactive substance concentrations for the MEIA (0.07 +/- 0.09 ng/ml) and
      FPIA assays (0.1 +/- 0.1 ng/ml) were statistically different (p = 0.01); however,
      no sample had a DLIS value >0.38 ng/ml. A poor correlation was noted between
      patient age, serum creatinine, total bilirubin, and DLIS concentration. The MEIA
      and FPIA assays effectively minimized DLIS cross-reactivity making both
      technologies clinically acceptable for serum digoxin measurement in pediatric
      patients with normal serum creatinine and total bilirubin.

PMID- 9631936
TI  - Bidirectional (positive/negative) interference in a digoxin immunoassay:
      importance of antibody specificity.
AB  - The importance of high specificity in immunoassays used in therapeutic monitoring
      is highlighted by a case study in which therapeutic-to-toxic borderline digoxin
      levels were measured by a digoxin immunoassay in the serum sample from a patient
      administered digitoxin rather than digoxin. The sample, mistakenly sent to the
      laboratory for digoxin analysis, gave discordant results in three digoxin
      immunoassays: 1.99 and 0.79 ng/ml in assays using polyclonal antibodies
      (fluorescence-polarization immunoassay and microparticle enzyme immunoassay,
      respectively), and <0.1 ng/ml in a chemiluminescent immunoassay using more
      specific monoclonal antibody. The presence of digitoxin (approximately 40 ng/ml)
      in the sample was confirmed by three different digitoxin immunoassays. Based on
      these results, the interference of different levels of digitoxin was studied in
      the presence of 0, 0.85, 1.9, and 4.7 ng/ml digoxin in all three digoxin assays.
      The chemiluminescent assay showed no significant interference. The fluorescence
      polarization immunoassay showed positive interference in all cases; however, the
      microparticle enzyme immunoassay showed a bidirectional interference: a positive
      interference observed at digoxin level <1.8 ng/ml, changing to a negative
      interference at higher digoxin concentrations. The authors conclude that in
      countries such as Germany, where both digoxin and digitoxin may be prescribed,
      caution should be used to interpret digoxin immunoassay results. Digoxin assays,
      with cross-reactivity to digitoxin <0.1% should be used.

PMID- 9631937
TI  - Validation of microdialysis sampling for subcutaneous extracellular valproic acid
      in humans.
AB  - This article is the second in a series of studies aimed at monitoring valproic
      acid pharmacokinetics in patients with epilepsy by subcutaneous microdialysis. In
      the current study, a detailed investigation on healthy volunteers is made of the
      relationship between total concentrations in plasma, free concentrations in
      plasma, and dialysate concentrations. Particular emphasis is put on validating
      that the in vivo recovery under standard conditions (30 mm dialyzing membrane and
      0.5 microl/minute perfusion rate) is sufficiently close to 100%. It was found
      that the recovery was very close to 100% at 0.5 microl/minute and by in vitro
      studies it could be excluded that valproic acid binds to the dialysis equipment.
      The correlation between unbound plasma concentrations and microdialysis
      concentrations of valproic acid was acceptable (r = 0.80), and they did not
      differ systematically from one another. It is concluded that microdialysis can be
      used to sample subcutaneous extracellular valproic acid in a clinical setting
      giving reliable estimates of the unbound concentration in plasma.

PMID- 9631938
TI  - Stone prevention: why so little progress?
AB  - Despite intensive research the knowledge of stone pathogenesis, which is the
      basis of every rational stone metaphylaxis, has remained rather scanty.
      Epidemiology shows that stone formation in most patients is only a sporadic
      event, probably resulting from a coincidence of different factors. The
      hypercalciuria, hypocitraturia, hyperuricosuria and hyperoxaluria frequently
      found in calcium stone formers can be influenced therapeutically and, in affluent
      societies, seem to be the result of protein over-consumption. These four factors
      favour crystallization processes in urine. However, urine is normally protected
      from nucleation, growth and aggregation of calcium minerals by crystallization
      inhibitors. In urine, crystallization of calcium oxalate can only be induced by
      an extreme supersaturation, a deficient inhibitor activity and promoters of
      crystallization. To form a stone, crystals have to be retained in the urinary
      collecting system. Two mechanisms of retention are discussed: large crystal
      aggregates trapped in collecting ducts of renal papillae, or a pre-existing
      calcification of the papilla (mainly calcium phosphate) that may be responsible
      for growth of an initially fixed particle to a concretion large enough to become
      symptomatic. An excessive oxalate intake combined with a low calcium consumption
      can produce marked hyperoxaluria. In the animal model, hyperoxaluria induces not
      only calcium oxalate crystallization but also papillary damage and incrustations.
      Hypercalciuria at a low pH favours the aggregation of calcium oxalate, and at a
      high pH the crystallization of calcium phosphate, a promoter of heterogeneous
      nucleation of calcium oxalate. All these factors and further complex phenomena
      mentioned in this paper have to be taken in account to perform rational stone
      metaphylaxis.

PMID- 9631939
TI  - Effect of citrate and pyrophosphate on the stability of calcium oxalate
      dihydrate.
AB  - The effect of citrate and pyrophosphate on the stability of calcium oxalate
      dihydrate (COD) was studied in an aqueous solution over 7 days. COD was
      precipitated from 1.0 x 10(-2) mol/l calcium oxalate solution with the addition
      of citrate and/or pyrophosphate and separated by centrifugation immediately, 48 h
      and 7 days after the precipitation. The percentage of COD in the precipitate,
      determined by X-ray diffraction, increased with a rise in citrate or
      pyrophosphate concentration and reached > or =90% at a citrate concentration of
      1.0 x 10(-3) mol/l or a pyrophosphate concentration of 2.0 x 10(-4) mol/l. The
      resulting COD was completely transformed into calcium oxalate monohydrate within
      48 h when the precipitate was composed of <90% COD. Nearly pure COD produced with
      pyrophosphate was stable over 7 days while that with citrate underwent partial
      transformation within 48 h. An additive effect of citrate and pyrophosphate was
      found on the stability of COD. It was concluded that a pyrophosphate
      concentration above a critical point was sufficient to prevent solution-mediated
      transformation of COD, and this critical point might be lowered to the
      physiological range with the presence of citrate.

PMID- 9631940
TI  - The effects of citrate and urinary macromolecules on the aggregation of
      hydroxyapatite crystals in solutions with a composition similar to that in the
      distal tubule.
AB  - The effects of citrate and dialysed urine (dU) on the aggregation of
      hydroxyapatite (HAP) crystals in solutions with different pH and otherwise with
      an ion composition assumed to correspond to that in the distal part of the distal
      tubule were studied by spectrophotometric assessment of the rate of crystal
      sedimentation. When the concentration of dU was increased from 1% to 20% we
      recorded an increased inhibition of HAP crystal aggregation at pH 6.5. There were
      no differences in the inhibition accomplished by 10% dU when the pH was varied
      between 5.5 and 7.0, but a lower inhibition was recorded at pH 7.5. Citrate in
      the range 0.05-4 mmol/l had a concentration-dependent inhibitory effect on HAP
      crystal aggregation. In the presence of 10% dU the net inhibitory effect of
      citrate was reduced at all pH levels. In the pH interval 5.5-7.0 a higher
      inhibition was recorded with 0.5 mmol/l citrate than with 10% dU, but in the
      presence of dU there was only a minor additional effect of citrate at
      concentrations below 0.5 mmol/l. These findings indicate that urinary
      macromolecules present in dU strongly inhibit HAP crystal aggregation under
      solution conditions corresponding to those in distal tubular urine. At the same
      nephron level citrate might have a direct inhibitory influence on the aggregation
      of HAP crystals, but in the presence of normal urinary macromolecules the
      additive inhibitory effect of citrate is probably only marginal.

PMID- 9631941
TI  - Glycoproteins in the urothelium and in the urine of the epidermal growth factor
      induced growing urinary tract in rats.
AB  - Systemic treatment with epidermal growth factor (EGF) induces growth of all wall
      layers of the urinary tract in pigs and rats. We have previously described that
      the EGF stimulated urothelium in Goettingen minipigs accumulates glycoproteins.
      The aim of the present study was to examine and partly characterize glycoproteins
      in the urothelium and in the urine from rats treated with EGF. Seventy-two female
      Wistar rats were allocated into five groups receiving EGF treatment (150
      microg/kg per day) for 0 (controls), 1, 2, 3 and 4 weeks before being killed.
      Glycoconjugates were characterized by means of lectins on tissue sections, and
      using Western blotting, in bladder extracts and in urine. The characterization
      mostly focused on the expression of the mucin-type core structures T and Tn using
      the lectins peanut agglutinin (PNA) and Vicia villosa (VVA) and specific
      monoclonal antibodies. The thickened EGF-stimulated urothelium retained the
      normal differentiation pattern as judged from the appearance on electron
      microscopy and from the expression of carbohydrate structures. Within the
      urothelium and in the urine there was increased expression of mucin-type
      glycoproteins suggesting increased urothelial production and excretion of mucin
      type glycoproteins. In conclusion, the EGF stimulated hyperplastic urothelium
      most probably excretes increased amounts of mucin-type glycoproteins to the urine
      but it retains the normal pattern of differentiation as assessed by lectin
      characterization.

PMID- 9631942
TI  - The effects of exogenous epidermal growth factor on the developing urinary tract
      in rats: a stereological description.
AB  - Systemic treatment with epidermal growth factor (EGF) induces growth of all wall
      layers of the urinary tract in pigs and rats. In this study, we describe the time
      dependent growth of the ureter and bladder. Forty-eight female Wistar rats were
      allocated into five groups receiving EGF treatment (150 microg/kg per day) for 0
      (controls), 1, 2, 3 or 4 weeks before being killed. The 24-h urine excretion was
      increased only in the group treated for 4 weeks with EGF. Measured by a simple
      infusion device, EGF significantly increased the bladder capacity by more than
      50% in all the EGF-treated groups. The volumes of the wall layers of the ureter
      and bladder were quantified using stereology. After 4 weeks of treatment with
      EGF, the total volumes of the ureter and bladder were 1.8- and 2.1-fold larger
      than in the control group (the urothelium was 2.8- and 3.5-fold larger and the
      muscular coat 1.6- and 1.6-fold larger in the ureter and bladder, respectively).
      In conclusion, the EGF-induced growth of the urinary tract is characterized by
      increased bladder capacity, and increased volume of all wall layers --most
      prominently the urothelium.

PMID- 9631943
TI  - Low-affinity nerve growth factor receptors (p75LNGFR) in human prostate tissue:
      stromal localisation.
AB  - Beta-nerve growth factor (beta-NGF) acts on high- and low-affinity receptors to
      effect sympathetic innervation. It is produced in the human prostate. This study
      aimed to demonstrate the presence of beta-NGF receptors and the distribution of
      p75LNGFR receptor protein in the human prostate. Radioligand binding assays were
      performed using microsomal preparations from benign prostatic hypertrophy (BPH)
      tissues but no specific binding of beta-NGF was demonstrated (n = 20).
      Furthermore, BPH and prostate cancer tissues were stained immunohistochemically
      for p75LNGFR. Immunohistochemistry localised p75LNGFR to tiny areas of prostate
      stroma postulated to be sympathetic nerves (BPH, n = 15; prostate adenocarcinoma,
      n = 15). Our results suggest that beta-NGF in the human prostate acts on stromal
      elements which, most likely, represent prostatic nerves. Beta-NGF may be an
      epithelial-stromal mediator of sympathetic nerve growth in the human prostate.

PMID- 9631944
TI  - CYP1A1 activity in renal cell carcinoma and in adjacent normal renal tissue.
AB  - Cytochrome P450-isoenzyme, CYP1A1, is responsible for the metabolic activation of
      several precarcinogenic environmental chemicals to their carcinogenic
      intermediates. Microsomal CYP1A1 activity in renal cell carcinoma (RCC) and in
      normal renal tissue was determined by measuring spectrofluorometrically the
      hydroxylation rate of benzo[a]pyrene. The study included 50 patients who
      underwent nephrectomy for RCC. Tissue specimens were taken from renal tumours
      and, as a control, from macroscopic normal renal tissue adjacent to the tumours.
      Normal renal tissues that were adjacent to poorly differentiated grade 3 tumours
      and/or to metastatic RCC contained significantly higher CYP1A1 activities than
      renal tissues next to well-differentiated (P = 0.02) and/or organ-confined
      tumours (P = 0.001). In conclusion, those patients who had tumours that could be
      considered aggressive on the grounds of poor cell differentiation or a metastatic
      feature of tumour, had remarkably higher CYP1A1 activities in their kidneys than
      the patients with less aggressive renal tumours.

PMID- 9631946
TI  - Evidence for the involvement of endothelial nitric oxide synthase from smooth
      muscle cells in the erectile function of the human corpus cavernosum.
AB  - Nitric oxide (NO) is an important mediator in the relaxation of cavernosal smooth
      muscle. The present study examines the existence and location of the constitutive
      isoform eNOS (endothelial NO synthase) accompanying the already substantiated
      neurogenic NOS (nNOS) in the human corpus cavernosum of men with and without
      erectile dysfunction. Activities of NOS enzymes were examined in specimens of 11
      potent and nine long-term impotent patients by means of light and electron
      microscopy using NADPH-diaphorase staining and immunohistochemical eNOS-specific,
      smooth muscle actin-specific and nNOS-specific markers. Cavernosal smooth muscle
      shows a distinct expression of eNOS. In contrast to the weaker expression of eNOS
      and nitrinergic innervation found in larger veins, the small intracavernosal
      helicine arteries express large quantities of eNOS and possess a dense
      nitrinergic innervation. Long-term impotent patients display a broad
      heterogeneity in eNOS expression and nitrinergic innervation while no overall
      correlation between NOS expression and erectile function was observed. The
      expression of eNOS indicates eNOS as a main source of NO alongside nNOS. The
      differentiated localization of eNOS supports at least a role of this isoform in
      vascular regulation.

PMID- 9631945
TI  - Influence of vinblastine on DNA parameters and multidrug resistance in renal cell
      carcinoma in vitro.
AB  - The purpose of this study was to investigate how the vinca alkaloid vinblastine
      influences DNA parameters and the mechanisms of multidrug resistance in renal
      cell carcinoma. After exposing cell cultures of human renal carcinoma to
      progressively increasing concentrations of vinblastine the cell lines were
      examined by flow cytometric DNA analysis to assess the S-phase and G2/M-phase
      fraction and by a modified MTT assay. It was shown that the exposed cells became
      P-glycoprotein-positive by staining the cells with a monoclonal antibody (JSB-1).
      The flow cytometric analysis revealed, with prolonged vinblastine exposure,
      correlated increases in the S-phase and G2/M-phase fractions (P = 0.0001). When
      vinblastine-free medium was used for culturing, the changed DNA characteristics
      returned to their original values. Comparing the DNA parameters with the IC50
      (concentration when cell growth is inhibited by 50%) we found a strong
      correlation between these parameters (P = 0.0001). In conclusion, DNA analysis of
      long-term vinblastine exposure may provide insight into events leading to
      multidrug resistance. Furthermore, analysis of the DNA profile might also be an
      important investigation before planning therapy with vinblastine for renal cell
      carcinoma.

PMID- 9631947
TI  - Does potassium induce the release of nitric oxide in the rabbit corpus
      cavernosum?
AB  - We investigated the effects of increases in the extracellular potassium
      concentration on the function of the rabbit corpus cavernosum. The resting tissue
      tension increased as the potassium concentration was increased from 4.7 mM to 20
      mM or 30 mM. The maximum contraction induced by 200 microM phenylephrine was
      significantly decreased in the presence of 30 mM potassium compared with 4.7 mM
      potassium. After precontraction was induced with 200 microM phenylephrine, the
      magnitude of field-stimulated relaxation increased significantly as the potassium
      concentration was increased from 4.7 mM to 10 or 20 mM, but was almost completely
      abolished at 30 mM potassium. There was no difference in the suppressive effect
      of L-NAME on field-stimulated relaxation between specimens treated with 4.7 mM or
      20 mM potassium. ATP- and bethanechol-induced relaxation was not affected by
      increases in the extracellular potassium concentration. A high-dose potassium
      solution (124 mM) induced contraction of the corpus cavernosum. In tissue
      precontracted with phenylephrine, a high-dose potassium solution that contained
      phenylephrine induced relaxation of corpus cavernosum; this relaxation was
      completely suppressed by L-NAME. These findings suggest that small increases in
      the extracellular potassium concentration increase field-stimulated relaxation of
      the corpus cavernosum and that this relaxation is not related to the effects of
      nitric oxide. Relaxation induced by high-dose potassium in tissue precontracted
      with phenylephrine is probably the result of release of nitric oxide.

PMID- 9631948
TI  - In vitro stimulation of renal tubular p-aminohippurate transport by dexamethasone
      in rat kidneys and in intact kidney tissue of patients suffering from renal cell
      carcinoma.
AB  - The aim of this study was to test whether or not the accumulation of p
      aminohippurate (PAH) can be increased in intact human renal cortical slices
      obtained from tumor-bearing kidneys of patients suffering from renal cell
      carcinoma (RCC). Tissue slices were incubated for 24 h in Williams medium E
      containing 0.01-50 microM dexamethasone. Thereafter slices were placed in PAH
      containing Cross-Taggart medium and PAH uptake into kidney tissue was measured
      for 2 h. In both rat and human renal tissue slices, PAH uptake capacity increased
      significantly in a concentration-dependent manner after 24 h of incubation in
      dexamethasone-containing medium (rat, 136%; man, 156%). The stimulatory effect
      was already significant after 12 h of incubation. In additional experiments it
      was shown that incubation in triiodothyronine (T3)-containing medium has
      different effects: in man, T3 does not influence the PAH accumulation capacity of
      renal cortical slices whereas in rats PAH accumulation is significantly lower
      after 24 h of incubation with T3. Thus stimulation of tubular transport capacity
      can be performed in vitro in human renal cortical slices. Discrepancies between
      the effects of dexamethasone and T3 indicate different modes of action of the two
      hormones at the cellular level.

PMID- 9631949
TI  - Muscarinic receptor subtypes in porcine detrusor: comparison with humans and
      regulation by bladder augmentation.
AB  - The properties of muscarinic acetylcholine receptors of porcine and human bladder
      detrusor were compared in radioligand binding studies using
      [3H]quinuclidinylbenzylate as the radioligand. The receptor affinity for the
      radioligand and the density of muscarinic receptors was similar in male and
      female pigs and in humans (Kd = 35 +/- 8 pM, Bmax = 153 +/- 30 fmol/mg protein).
      Atropine and subtype-selective antagonists had steep and monophasic competition
      curves in porcine and human detrusor with a rank order of potency of atropine >>
      hexahydro-sila-difenidol > or = AF-DX 116 > or = pirenzepine, indicating the
      presence of a homogeneous population of M2 muscarinic receptors. In female pigs
      bladder outflow obstruction generated by partial urethral ligation or its
      surgical treatment by ileum augmentation or autoaugmentation did not
      significantly alter expression of muscarinic receptors or of alpha2A
      adrenoceptors, but the power was insufficient to exclude alterations of less than
      60%. We conclude that porcine and human detrusor express muscarinic receptors of
      the M2 subtype; despite these qualitative similarities the use of the porcine
      model may be limited by large biological variance with regard to quantitative
      receptor expression.

PMID- 9631950
TI  - The discriminative stimulus properties of cocaine: effects of microinfusion of
      cocaine, a 5-HT1A agonist or antagonist, into the ventral tegmental area.
AB  - Serotonin (5-HT) afferents may modulate the dopamine mesoaccumbens circuit, which
      has been shown to be critically involved in the locomotor stimulatory,
      discriminative stimulus, and rewarding properties of cocaine. In the present
      study, we investigated the role of 5-HT1A receptors in the ventral tegmental area
      (VTA) in mediating the discriminative stimulus effects of cocaine. Male Sprague
      Dawley rats were trained to discriminate cocaine (10 mg/kg) from saline in a two
      lever, water-reinforced FR 20 task. After acquiring the cocaine-saline
      discrimination, rats were stereotaxically implanted with bilateral guide cannulae
      into the VTA or adjacent substantia nigra reticulata (SNR). Intraperitoneal
      administration of cocaine (0.625-10 mg/kg) produced a dose-related increase in
      drug-lever responding. Both intra-VTA and intra-SNR infusion of cocaine (12.5-50
      microg/0.5 microl/side) engendered primarily saline-like responding.
      Microinjection of the 5-HT1A agonist 8-hydroxy-2-(di-N-propylamino) tetralin
      (DPAT; 0.1-10 microg/0.5 microl/side) or the 5-HT1A antagonist WAY 100635 (0.01
      1.0 microg/0.5 microl/side) into the VTA or SNR did not substitute for the
      systemic cocaine cue. Further, intra-VTA or intra-SNR DPAT or WAY 100635 in
      combination with systemic doses of cocaine did not alter (i.e., attenuate or
      potentiate) the systemic cocaine cue. Overall, these data indicate that 5-HT1A
      receptors in the VTA do not mediate or modulate the discriminative stimulus
      effects of cocaine in the rat.

PMID- 9631951
TI  - Effects of drugs of abuse and scopolamine on memory in rats: delayed spatial
      alternation and matching to position.
AB  - Drugs of abuse produce amnestic effects in humans and laboratory animals in a
      variety of tasks. Generally, only a few compounds have been examined in any
      particular procedure. It was the goal of the present studies to examine drugs of
      abuse of different pharmacological classes in rats responding under two
      behavioral schedules historically employed as experimental models of memory:
      spatial alternation and matching to position. One group of rats responded under a
      single-response spatial-alternation baseline with a 10-s delay and another group
      responded under a matching-to-position baseline with delay values of 3, 10 and 30
      s. Performance under the spatial-alternation baseline was characterized by low
      variability and >90% accuracy. Under the matching-to-position baseline, saline
      control percent accuracy was >95% at 3 s, >85% at 10 s and >70% at 30 s. Under
      spatial alternation cocaine, d-amphetamine, pentobarbital, diazepam,
      phencyclidine, scopolamine and methscopolamine produced significant (P<0.05)
      effects on accuracy, whereas only cocaine, d-amphetamine, pentobarbital and
      phencyclidine disrupted accuracy under the matching-to-position baseline. These
      results suggest that spatial alternation may be a more sensitive baseline for
      determining drug effects on working memory in the rat.

PMID- 9631952
TI  - Effects of pergolide on intravenous cocaine self-administration in men and women.
AB  - Clinical evidence suggests that pergolide, a D1/D2 dopamine receptor agonist, may
      be useful in maintaining cocaine abstinence. We investigated pergolide's effects
      in a laboratory model of IV cocaine self-administration by humans. Twelve
      inpatient volunteers (7M, 5F), who reported spending an average of $170/week on
      cocaine, received pergolide (0.05 mg BID) for 8 days and placebo for 8 days, with
      drug order balanced across subjects. Self-administration sessions occurred on the
      last 4 days of maintenance on each medication. A modified seven-trial progressive
      ratio choice procedure (0, 8, 16, 32 mg/70 kg cocaine versus $5) was utilized,
      with sessions consisting of: (a) two sample trials, where participants responded
      to receive the dose and tokens available that day, and (b) five choice trials,
      where participants chose between the available dose and tokens. Following each
      trial, the response requirement for the chosen option increased by 400.
      Maintenance on pergolide 1) decreased cocaine-induced increases in ratings of
      "High," "Stimulated," cocaine "Potency," estimates of street value, and heart
      rate, 2) increased ratings of "I want cocaine," and 3) had no effect on cocaine
      self-administration. The increased desire to use cocaine during pergolide
      maintenance suggests that it has limited treatment utility at this dose, but
      given the attenuation of cocaine's subjective and cardiovascular effects, an
      investigation of a wider range of pergolide doses on cocaine self-administration
      and subjective effects is warranted.

PMID- 9631953
TI  - Effects of amperozide, 8-OH-DPAT, and FG 5974 on operant responding for ethanol.
AB  - Both 5-HT1A and 5-HT2A receptors have been implicated in modulating ethanol self
      administration. A novel serotonergic compound, FG 5974, with combined 5-HT1A
      agonist/5-HT2A antagonist activities, has shown effects in decreasing ethanol
      consumption in two-bottle choice paradigms. In the present study, the effect of
      this compound on operant responding for ethanol (as well as water and a saccharin
      solution) was compared to compounds possessing the separate neuropharmacological
      effects of this drug (the 5-HT1A agonist, 8-OH-DPAT, and the 5-HT2A antagonist,
      amperozide). While all three serotonergic compounds decreased operant responding
      for ethanol, only FG 5974 had no effect on water and saccharin responding. These
      results suggest that combined 5HT1A agonist/5-HT2A antagonist activity provides a
      more selective effect on ethanol reinforcement than either neuropharmacological
      action alone. Therefore, further analysis of mixed serotonergic compounds in
      general, and FG 5974 in particular, is warranted as they offer potential
      treatments for alcoholism.

PMID- 9631954
TI  - The effects of dopaminergic agents on reaction time in rhesus monkeys.
AB  - Many CNS pathologies, including Parkinson's, Alzheimer's and Huntington's
      diseases, as well as AIDS dementia complex, involve some degree of movement
      dysfunction. Reaction time (RT) performance has been shown to be a sensitive
      measure of motor function for these disorders. Useful models of RT performance
      exist in a variety of species, but few are performed in the same manner as with
      humans. To facilitate species comparisons, the present RT task was developed from
      a human RT task. Dopaminergic drugs were then used to characterize the
      sensitivity of the model to CNS changes and to investigate their effects on RT
      performance in intact rhesus monkeys. With cumulative dosing, the selective
      dopamine receptor antagonists (D1) SCH 39166 and (D2) raclopride produced dose
      dependent slowing of RT performance. Results following bolus administration of
      these drugs were consistent with the cumulative dosing procedure, although of
      smaller magnitude and higher variability. Amphetamine had no significant effect
      on group RT performance with either dosing scheme, but RT performance in
      individual monkeys was either speeded or slowed by d-amphetamine. The present
      results suggest that blockade of either D1-like or D2-like dopamine receptors can
      slow RT performance in rhesus monkeys and that this paradigm may be useful to
      study movement dysfunction in non-human primates.

PMID- 9631955
TI  - Serotonin receptors in the caudal brainstem are necessary and sufficient for the
      anorectic effect of peripherally administered mCPP.
AB  - The role of caudal brainstem 5-HT receptors in mediating the anorectic effect of
      the direct 5-HT2C/1B agonist, mCPP [1-(3-chlorophenyl)piperazine
      dihydrochloride], was evaluated. We demonstrated, first, that systemic injections
      of mCPP yielded a dose-related suppression of intra-oral intake of 12.5% glucose
      in intact rats and in chronically maintained supracollicular decerebrate rats.
      The results of the decerebrate experiment suggest that 5-HT receptors in the
      caudal brainstem are sufficient for mediating the drug's intake effect. We also
      showed a dose-related intake suppression when mCPP was delivered to the fourth
      ventricle of intact rats, with potent suppression obtained at doses well below
      threshold for systemic administration. Whether and to what extent the 5-HT2C/2A
      antagonist, mesulergine reverses the intake suppression that follows systemic or
      4th i.c.v. injection of mCPP was examined. Fourth i.c.v. co-administration of
      mesulergine (60 microg) and mCPP (40 microg) eliminated the approximately 50%
      intake suppression observed when mCPP was delivered alone, a result that affirms
      the receptor selectivity of the 4th i.c.v. agonist effect. We showed, further,
      that 4th i.c.v.mesulergine (60 microg) completely reversed the intake suppression
      produced by systemic mCPP (2 mg/kg). The latter result indicates that stimulation
      of 5-HT receptors in the caudal brainstem is necessary for the intake suppression
      produced by systemic administration of this 5-HT agonist in the intact rat.

PMID- 9631956
TI  - Chronic haloperidol produces a time- and dose-related slowing of lick rhythm in
      rats: implications for rodent models of tardive dyskinesia and neuroleptic
      induced parkinsonism.
AB  - In order to characterize the development of orolingual motor effects of chronic
      haloperidol treatment in rats, this typical neuroleptic was administered for 102
      days while daily measurements of tongue movement dynamics (peak force, lick
      rhythm, number of licks) during water licking were recorded. After chronic
      haloperidol dosing (vehicle, 0.06. 0.12, 0.24 mg/kg for four separate groups) for
      32 days and continuing every second or third day of the chronic dosing period,
      the effects of cholinergic (scopolamine: 0.05-0.20 mg/kg; trihexyphenidyl: 0.15
      1.0 mg/kg) or serotonergic (ritanserin: 0.5-4.0 mg/kg; quipazine: 0.5-4.0 mg/kg)
      probe drugs were examined for their capacity to antagonize the alterations in
      licking behavior induced by haloperidol. Haloperidol dose-dependently reduced
      peak force and number of licks, effects which were apparent within 2 or 3 days of
      the start of treatment. Significant effects of haloperidol on lick rhythm first
      emerged on day 13 and gradually increased in magnitude through the remaining
      treatment period. Scopolamine, trihexyphenidyl, and quipazine reduced
      haloperidol's effects on at least one measure of licking behavior. During a 7-day
      haloperidol withdrawal period, the four dosage groups were similar on all
      measures of tongue dynamics. Overall, the results exhibited features suggesting
      the co-occurrence of Parkinson-like and tardive dyskinesia-like effects.

PMID- 9631957
TI  - Effects of subchronic administration of clozapine, thioridazine and haloperidol
      on tests related to extrapyramidal motor function in the rat.
AB  - Clozapine, thioridazine (THIO) and haloperidol were administered for 14
      consecutive days, and separate groups of rats were used to study the effects of
      these drugs on tremulous jaw movements and lever pressing. Rats were observed on
      day 13 for the ability of the antipsychotic drugs to induce jaw movements.
      Haloperidol produced a dose-related increase in jaw movements, while clozapine
      and THIO failed to induce jaw movements. On day 14, rats were challenged with 5.0
      mg/kg of the anticholinesterase tacrine, which induces a very high level of jaw
      movement activity. Clozapine significantly reduced tacrine-induced tremulous jaw
      movements, while haloperidol did not. Although previous work had shown that acute
      THIO could suppress jaw movements, repeated THIO failed to do so. In order to
      provide an additional behavioral test for comparisons of the relative potencies
      of the antipsychotic drugs, rats were tested for the effects of these drugs on
      fixed ratio 5 lever pressing. All three drugs significantly suppressed lever
      pressing. Haloperidol showed sensitization with repeated injections, while
      clozapine showed tolerance. Data were analyzed by taking the ratio of the ED50
      for suppression of tacrine-induced jaw movement over the ED50 for suppression of
      lever pressing on day 14. Clozapine reduced tacrine-induced jaw movements in a
      dose range slightly lower than that required for reduction of lever pressing. In
      contrast, THIO and haloperidol failed to affect tacrine-induced jaw movements
      even at doses that were 5-18 times the ED50 for suppression of lever pressing.
      Thus, tests of jaw movement activity and lever pressing after repeated
      administration may be useful for assessing atypical antipsychotic drugs.

PMID- 9631958
TI  - The rate-decreasing effects of fentanyl derivatives in pigeons before, during and
      after chronic morphine treatment.
AB  - Mirfentanil is a fentanyl derivative with non-opioid actions, including non
      opioid antinociceptive effects in rhesus monkeys. The current study examined the
      rate-altering effects of mirfentanil and several other compounds in pigeons to
      assess: 1) the opioid and non-opioid actions of acutely-administered fentanyl
      derivatives; and 2) the development of cross-tolerance between each of these
      compounds and morphine. Seven pigeons responded under a fixed-ratio 20 (FR20)
      schedule of food delivery. In untreated pigeons, fentanyl, morphine, naltrexone,
      ketamine and three fentanyl derivatives (mirfentanil, OHM3463 and OHM3295)
      decreased rates of key pecking in a dose-related manner. Naltrexone (0.1-1.0
      mg/kg) attenuated the effects of OHM3463 and not mirfentanil or OHM3295,
      suggesting non-opioid mediation of the rate-decreasing effects for the latter two
      fentanyl derivatives. Subjects were treated daily with morphine for 9 weeks, up
      to a dose of 100 mg/kg per day, during which time the dose-effect curves for
      morphine, fentanyl and OHM3463 shifted rightward 6-, 10- and 2-fold,
      respectively, indicating the development of tolerance to morphine and cross
      tolerance to fentanyl and OHM3463. Dose-effect curves for ketamine, OHM3295 and
      mirfentanil were not shifted to the right during morphine treatment, and the dose
      effect curve for naltrexone was shifted leftward 180-fold. To the extent that
      rate-decreasing effects are predictive of antinociceptive effects, these data
      suggest that some fentanyl derivatives might be useful therapeutics under
      conditions where tolerance develops to morphine-like opioids.

PMID- 9631959
TI  - Reduction of 3,4-diaminopyridine-induced biogenic amine synthesis and release in
      rat brain by gabapentin.
AB  - The anticonvulsant drug gabapentin has been shown recently to exhibit anxiolytic
      and analgesic actions in animals. Such actions have been postulated in part to
      reflect effects on biogenic amine neuronal activity. Therefore the effects of
      gabapentin on biogenic amine neuronal activity were assessed by measuring the
      synthesis of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) in rat brain
      and on the release of [3H] NE from rat hippocampal slices both in the presence
      and absence of the depolarizing agent 3,4-diaminopyridine (DAP). Gabapentin (30
      and 100 mg/kg, i.p.) did not alter the basal synthesis rates of NE and DA as
      assessed by the unchanged accumulation of L-dihydroxyphenylalanine (DOPA) in the
      NE-enriched hippocampus and cortex and in the DA-enriched striatum and mesolimbic
      areas. Gabapentin also did not alter 5-HT synthesis as determined by the
      unaltered accumulation of 5-hydroxytryptophan (5-HTP) in the same brain areas.
      DAP (2 mg/kg, i.p.) induced a modest but significant increase in DOPA
      accumulation in the hippocampal, mesolimbic and striatal regions. This DAP
      induced increase in DOPA accumulation was antagonized significantly in the
      hippocampus and mesolimbic regions by gabapentin at 30 and 100 mg/kg and in
      striatum by 100 mg/kg; a 10 mg/kg dose was inactive. DAP increased selectively 5
      HT synthesis in hippocampus and this effect was blocked by gabapentin. These
      findings indicate that the increased synthesis of biogenic amines induced by DAP
      is antagonized by gabapentin. In support of the in vivo studies, gabapentin was
      also shown to inhibit the DAP-evoked release of [3H]NE from hippocampal slices.
      Although the underlying mechanism for these effects is unclear, the present
      findings nevertheless demonstrate that gabapentin has inhibitory effects on
      stimulated NE, DA and 5-HT neurons that may be involved in explaining in part the
      CNS effects of this drug.

PMID- 9631960
TI  - Dietary additives and the acquisition of cocaine self-administration in rats.
AB  - The effects of dietary caffeine and the amount and palatability of food on the
      acquisition of cocaine (0.2 mg/kg) self-administration were examined. Using an
      autoshaping procedure, seven groups of 13 rats each were trained to press a lever
      resulting in a cocaine (0.2 mg/kg infusion under a fixed-ratio 1 (FR 1) schedule.
      One group had ad libitum access to caffeine- (0.2% w/w) admixed food. Three
      groups had access to 10 g, 20 g or ad lib food each day. Another three groups had
      the same three amounts of ground food with powdered saccharin (0.2% w/w) added.
      During daily 6-h autoshaping sessions, ten infusions were delivered each hour
      under a random-time 90-s schedule after a brief (15 s) extension of a retractable
      lever. These were followed by 6-h self-administration sessions, when the lever
      remained extended and cocaine infusions were available under an FR 1 schedule.
      The acquisition criterion was self-administration of a mean of 100 infusions over
      5 days. Cocaine self-administration was accelerated in the caffeine group
      compared to the regular chow group. However, by 30 days nearly the same
      percentage of rats in the caffeine and regular food groups met the acquisition
      criterion. In the other six groups, as the amount of food increased, the rate of
      acquisition and percentage of rats per group meeting the acquisition criterion
      decreased. In the ad lib group, acquisition was further reduced when saccharin
      was added to food. In summary, dietary caffeine accelerated acquisition and a
      greater amount and increased palatability of food independently interfered with
      acquisition of cocaine self-administration in rats.

PMID- 9631961
TI  - The influence of environment on the induction of sensitization to the psychomotor
      activating effects of intravenous cocaine in rats is dose-dependent.
AB  - The acute psychomotor response and development of sensitization to amphetamine is
      attenuated if i.p. injections are given in the cage where a rat lives relative to
      when injections are given in a novel but physically identical test environment.
      Furthermore, when the environmental cues predicting i.p. injections are
      completely eliminated by using remotely activated i.v. injections in the home
      cage, 1.0 mg/kg amphetamine produces a very small acute response and no
      sensitization. The same treatments do produce sensitization if i.v. injections
      are signaled by placement of the rat in a novel test cage. The present experiment
      was designed to determine if there is a similar effect of environmental condition
      on the response to i.v. cocaine, and to what extent the effect may be dose
      dependent. This was accomplished by comparing the psychomotor activating effects
      (rotational behavior) of repeated i.v. administrations of one of eight doses of
      cocaine (0.0, 0.3, 0.6, 1.2, 2.4, 3.6, 4.8, or 7.2 mg/kg) given in the home cage,
      with infusions of the same doses given in a novel test cage. There was no effect
      of environment on the acute psychomotor response to cocaine. There was, however,
      a significant effect of environment on the induction of sensitization. A higher
      dose of cocaine was required to induce sensitization when i.v. administrations
      were given in the home cage than when they were given in a physically identical
      but novel test environment. At high doses, however, cocaine induced sensitization
      regardless of environmental condition. The results suggest that the effect of
      this environmental manipulation is to shift the dose-effect curve for the
      induction of sensitization, and support the notion that the ability of
      psychostimulant drugs to induce sensitization can be modulated by the
      circumstances surrounding drug administration.

PMID- 9631962
TI  - Efficacy of administration of dexfenfluramine and phentermine, alone and in
      combination, on ingestive behavior and body weight in rats.
AB  - Recently, a combination of the anorectics fenfluramine (FEN) and phentermine
      (PHEN) has been used to treat obesity. While each of these agents has been
      investigated in animals, little is known concerning the effects of the
      combination on ingestive behavior and body weight. In the present experiments, we
      report: (1) the effects of acute administration of dexfenfluramine (DFEN) and
      PHEN individually and in combination on sweetened milk intake and body weight in
      non-deprived rats and (2) the effects of chronic administration (7 day minipump)
      of DFEN, PHEN, and their combination on daily food intake and body weight both
      during and after the treatment period. Additionally, the effects of the 5-HT2C
      agonist 1-[3-(trifluoromethyl)-phenyl]piperazine (TFMPP) alone and in combination
      with PHEN on food intake and body weight were assessed. Both acute and chronic
      administration of DFEN and PHEN revealed that in combination they are more
      effective than when given individually. However, the DFEN/ PHEN combination does
      not appear to exert effects that are selective for food intake because water
      intake was markedly suppressed in water-deprived rats. PHEN alone or in
      combination with either DFEN or TFMPP also produced increased activity or
      alertness during the day when controls normally were asleep. While anorectic
      combinations such as DFEN/PHEN may be effective at promoting weight loss and
      reducing food intake, future studies on their specificity, safety and efficacy
      are warranted.

PMID- 9631963
TI  - Correlation of resting first-pass left ventricular ejection fraction and resting
      myocardial infarct size.
AB  - This study determined the correlation between the extent of the resting perfusion
      defect by technetium-99m sestamibi tomographic imaging and the first-pass left
      ventricular (LV) ejection fraction (EF). A total of 1,955 patients underwent
      technetium-99m sestamibi tomographic imaging with measurement of first-pass
      resting LVEF. Twenty-five percent of patients had a prior history of myocardial
      infarction. First-pass LVEF was measured using a peripheral intravenous injection
      and a multicrystal gamma camera with standard software. Resting tomographic
      perfusion defect size (infarct size) was quantitated using previously published
      methods. Mean LVEF for the study group was 0.60 +/- 0.11. Mean LV infarct size
      was 5 +/- 11%. For the 1,265 patients (65% of the study group) with no measurable
      perfusion defect, the prevalence of a normal (> or = 0.50) LVEF was 96% (1,212 of
      1,265 patients). For patients with a measurable defect (n = 690, 35%), the
      inverse linear correlation with LVEF was highly significant (r = -0.60, p
      <0.0001) but with wide confidence limits (SEE = 10 LVEF points), thereby limiting
      the predictive value in individual patients. Thus, in the absence of known
      cardiomyopathy, valvular heart disease, or left bundle branch block, patients
      without a quantifiable resting perfusion defect are highly likely to have a
      normal resting LVEF and may not require determination of LV function. For
      patients with resting perfusion defects, LVEF cannot be predicted with confidence
      and should therefore be measured.

PMID- 9631964
TI  - In-hospital and late results of coronary stents versus conventional balloon
      angioplasty in acute myocardial infarction (GRAMI trial). Gianturco-Roubin in
      Acute Myocardial Infarction.
AB  - One hundred four patients presenting with acute myocardial infarction < 24 hours
      after onset were randomized to 2 groups: group I (n = 52) was treated with
      balloon angioplasty followed electively with Gianturco Roubin II stents, and
      group II was treated with conventional balloon angioplasty alone (n = 52). All
      lesions were suitable for stenting. Baseline clinical, demographic, and
      angiographic characteristics were similar in the 2 groups. Procedural success was
      defined as no laboratory death or emergent coronary bypass, Thrombolysis In
      Myocardial Infarction (TIMI) trial 2 or 3 flow after the procedure in a culprit
      vessel, and a residual stenosis < or = 30% for coronary angioplasty and < 20% for
      stent. Procedural success was 98% in group I versus 94.2% in group II, p = NS.
      Thirteen patients in group II (25%) had bailout stenting during the initial
      procedure. Adverse in-hospital events including either death, nonelective
      coronary bypass, recurrent ischemia, and reinfarction occurred in 3.8% in group I
      versus 19.2% in group II, p = 0.03. Repeat angiography performed routinely before
      hospital discharge revealed TIMI 3 flow in the infarct-related artery in 98% in
      group I versus 83% in group II, p < 0.03. At late follow-up, event-free survival
      was significantly better in the stent (83%) than in the coronary angioplasty
      (65%) group (p = 0.002). The procedural in-hospital and late outcomes of this
      randomized study demonstrate that balloon angioplasty followed electively by
      coronary stents can be used as the primary modality for patients undergoing
      coronary interventions for acute myocardial infarction, increasing TIMI 3 flow,
      reducing in-hospital adverse events, and improving late outcome compared with
      balloon angioplasty alone.

PMID- 9631965
TI  - Changes in absolute and relative importance in the prognostic value of left
      ventricular systolic function and congestive heart failure after acute myocardial
      infarction. TRACE Study Group. Trandolapril Cardiac Evaluation.
AB  - Changes in the importance of left ventricular (LV) systolic dysfunction and
      congestive heart failure (CHF) with time after an acute myocardial infarction
      (AMI) after the introduction of thrombolytic therapy have not been studied. LV
      systolic function, measured as wall motion index (WMI) by echocardiography, was
      assessed in 6,676 consecutive patients with an enzyme-confirmed AMI. So that
      changes in the prognostic value of WMI or CHF could be studied, separate analyses
      were performed at selected time periods. Average monthly mortality (deaths per
      100 patients per month) was determined from life-table analyses, with groups
      divided by WMI above and below 1.2 (a WMI > 1.2 corresponds to an ejection
      fraction > 0.35) or by presence and/or absence of CHF. Relative risk (95%
      confidence intervals [CI]) was determined by proportional hazard models,
      including baseline characteristics. In patients with LV dysfunction or CHF,
      monthly mortality was high during the first month (18.3 +/- 1.6% and 20.2 +/-
      1.6%, respectively), decreased during the first year, and was stable thereafter
      (0.8 +/- 0.1% and 1.0 +/- 0.1%, respectively, average monthly mortality after
      year 3). The relative risk of LV dysfunction decreased from 2.4 (CI 2.0 to 2.9)
      to 1.3 (CI 1.0 to 1.6) in the same period. The relative risk of CHF decreased
      from 2.9 (CI 2.3 to 3.8) to 1.6 (CI 1.3 to 2.0). In patients without LV
      dysfunction or CHF, monthly mortality was relatively high during the first month
      (5.2% +/- 0.7% and 3.4% +/- 0.6%, respectively) but decreased within the first
      year to low, stable values (0.6% +/- 0.1% and 0.4% +/- 0.1%, respectively,
      average monthly mortality after year 3). In patients who received thrombolytic
      therapy, the relative risk associated with a WMI < or = 1.2 decreased from 3.0
      (CI 2.0 to 4.4) to 1.3 (CI 0.9 to 1.6) and from 3.2 (CI 2.0 to 5.1) to 1.7 (CI
      1.2 to 2.4) in patients with CHF. The risk of dying decreases steeply with time
      after an AMI with or without LV dysfunction or CHF and stabilizes at low values
      after 1 year. This is in contrast to the relative importance of these risk
      factors, which is maintained for > or = 5 years but decreases with time.

PMID- 9631966
TI  - Paradoxic decreases in atherosclerotic plaque mass in insulin-treated diabetic
      patients.
AB  - This study assessed the impact of diabetes mellitus on atherosclerotic lesion
      formation. Seventy insulin-treated diabetics, 150 non-insulin-treated diabetics,
      and 607 nondiabetics with chronic anginal syndromes and de novo native coronary
      stenoses were studied using (1) angiography, and (2) intravascular ultrasound
      (reference and lesion arterial, lumen, and plaque areas; area stenosis [reference
      lesion/reference lumen area]; remodeling index [reference-lesion lumen
      area/lesion-reference plaque area]; and slope of the regression line relating
      lumen area to plaque burden [plaque/arterial area]). Despite being diabetic for
      longer and having similar lumen compromise, insulin-treated patients had (1) less
      reference plaque (8.3 +/- 3.4 vs 10.5 +/- 4.5 mm2, p = 0.0015), (2) less stenosis
      plaque (13.0 +/- 4.9 vs 16.9 mm2, p <0.0001), (3) smaller reference arterial
      areas (17.1 +/- 5.4 vs 19.7 +/- 6.2 mm2, p = 0.0063), and (4) smaller stenosis
      arterial areas (15.3 +/- 4.9 vs 19.5 +/- 6.5 mm2, p <0.0001) than non-insulin
      treated diabetics. With use of multivariate linear regression analysis, insulin
      use was an independent (and negative) predictor of reference plaque and arterial
      areas (p = 0.0308 and p = 0.0179) and stenosis plaque and arterial areas (p =
      0.0117 and p = 0.0066). This was also true when normalized for body surface area.
      The remodeling index showed that insulin treatment resulted in an exaggerated
      impact of plaque accumulation on lumen compromise. This was confirmed by the
      slope of the regression line relating lumen area to plaque burden. Patients with
      a longer duration of diabetes who were treated with insulin for > or = 1 year had
      (paradoxically) less reference segment and stenosis plaque accumulation. Possible
      explanations include impaired adaptive remodeling and/or arterial (and plaque)
      shrinkage.

PMID- 9631967
TI  - A national survey of emergency department chest pain centers in the United
      States.
AB  - Although chest pain centers are promoted as improving emergency cardiac care, no
      data exist on their structure and processes. This national study determines the
      1995 prevalence rate for emergency department (ED)-based chest pain centers in
      the United States and compares organizational differences of EDs with and without
      such centers. A mail survey was directed to 476 EDs randomly selected from the
      American Hospital Association's database of metropolitan hospitals (n = 2,309);
      the response rate was 63%. The prevalence of chest pain centers was 22.5% (95%
      confidence interval 18% to 27%), which yielded a projection of 520 centers in the
      United States in 1995. EDs with centers had higher overall patient volumes,
      greater use of high-technology testing, lower treatment times for thrombolytic
      therapy, and more advertising (all p <0.05). Hospitals with centers had greater
      market competition and more beds per annual admissions, cardiac catheterization,
      and open heart surgery capability (all p <0.05). Logistic regression identified
      open heart surgery, high-admission volumes, and nonprofit status as independent
      predictors of hospitals having chest pain centers. Thus, chest pain centers have
      a moderate prevalence, offer more services and marketing efforts than standard
      EDs, and tend to be hosted by large nonprofit hospitals.

PMID- 9631968
TI  - Effects of meal ingestion and active standing on blood pressure in patients > or
      = 60 years of age.
AB  - Postprandial hypotension and orthostatic hypotension occur often in elderly
      patients. In the present study, we examined hemodynamic and humoral responses to
      meal ingestion and active standing in 20 patients > or = 60 years of age who were
      free of apparent autonomic and cardiac dysfunction. For a time-control study,
      water was given instead of a meal to 19 of the 20 patients. After the meal
      ingestion, there was a fall in systolic blood pressure (BP) in 6 patients of > 20
      mm Hg, whereas the fall in systolic BP during the control study was not > 20 mm
      Hg in any patient. The low-frequency power of the systolic BP wave, an index of
      peripheral sympathetic activity, was significantly increased only in the patients
      without postprandial hypotension. The postprandial changes in systolic BP were
      correlated with the changes in the low-frequency power of the systolic BP wave (r
      = 0.61; p < 0.01), but they were not correlated with the changes in plasma
      norepinephrine, insulin, cardiac output, or parameters obtained by the spectral
      analysis of the RR interval. The systolic BPs in the upright position were
      comparable after the meal and the water ingestion. Thus, the effects of meal
      ingestion and upright position on BP are not additive. Dysfunction of peripheral
      sympathetic control of vascular tone may contribute to the postprandial
      hypotension in elderly patients.

PMID- 9631969
TI  - Elective carotid artery stenting in the presence of contralateral occlusion.
AB  - Significant carotid stenosis in the presence of an occluded contralateral artery
      has a poor prognosis with medical therapy alone. Carotid cross clamping during
      surgical endarterectomy results in critical flow reductions in patients with
      inadequate collateral flow, and represents a significant risk for procedural
      strokes. Carotid stenting is being evaluated as an alternative to endarterectomy.
      We describe the immediate and late outcome of a series of 26 patients treated
      with carotid stenting in the presence of contralateral carotid occlusion. The
      mean age of the patients in this group was 65 +/- 9 years, 23 (89%) were men and
      10 (39%) were symptomatic from the vessel treated. The procedural success of
      carotid stenting in this group of patients was 96%. The mean diameter stenosis
      was reduced from 76 +/- 15% to 2.8 +/- 5%. There was 1 (3.8%) minor stroke in a
      patient who developed air embolism during baseline angiography. At late follow-up
      there was no neurologic event in any patient at a mean of 16 +/- 9.5 months after
      the procedure. Thus, carotid stenting of lesions with contralateral occlusion can
      be performed successfully with a low incidence of procedural neurologic
      complications and late stroke.

PMID- 9631971
TI  - William Howard Frishman, MD: a conversation with the editor. Interview by William
      Clifford Roberts.

PMID- 9631970
TI  - Diagnostic and prognostic implications of left ventricular cavity obliteration
      response to dobutamine echocardiography.
AB  - Left ventricular (LV) cavity obliteration during dobutamine echocardiography (DE)
      indicates a vigorous inotropic response to stress. Such a response may suggest
      the absence of coronary artery disease (CAD), but a small LV cavity may also
      preclude recognition of wall motion abnormalities. We sought to determine the
      frequency, correlates, accuracy, and prognostic value of the LV cavity
      obliteration response in 336 consecutive patients who underwent coronary
      angiography within 1 year of DE. Cavity obliteration was defined by contact of
      the opposite walls in the apical views during DE, and ischemia by detection of a
      new or worsening wall motion abnormality. Sensitivity was based on comparison
      with coronary anatomy in 220 patients without prior revascularization. The
      prognostic implications of cavity obliteration were examined by follow-up of 324
      patients (96%) over 23 +/- 9 months for death, myocardial infarction, and late
      revascularization. Cavity obliteration was present in 86 of the 336 DE studies
      (26%). Baseline and stress hemodynamics were not predictive of cavity
      obliteration, which was associated with LV hypertrophy and female gender (p
      <0.0001), and inversely related to LV systolic dysfunction and use of angiotensin
      converting enzyme inhibitors or diuretics (p <0.02). The sensitivity of DE was
      less in patients with cavity obliteration than the remainder, especially in
      single vessel (46% vs 92%, p <0.001) but also in multivessel CAD (73% vs 95%, p =
      0.01). Irrespective of DE and angiographic results, cavity obliteration was a
      negative predictor for cardiac events (RR 0.42, 95% confidence interval [CI] 0.21
      to 0.87, p = 0.02) and death (RR 0.14, 95% CI 0.02 to 1.09, p = 0.06). Even after
      exclusion of patients with LV dysfunction, cavity obliteration was an independent
      predictor of freedom from events (RR 0.41, 95% CI 0.19 to 0.88, p = 0.02). Thus,
      LV cavity obliteration is a frequent response to DE, which compromises the
      sensitivity of DE but is correlated paradoxically with a favorable clinical
      outcome.

PMID- 9631972
TI  - Implications of left ventricular remodeling in hypertrophic cardiomyopathy.
AB  - Left ventricular remodeling occurs spontaneously among patients with hypertrophic
      cardiomyopathy in several ways: (1) wall thickening in children; (2) wall
      thinning associated with cavity enlargement in midlife; and possibly (3) a very
      gradual wall thinning process occurring over long periods of time in adulthood.

PMID- 9631973
TI  - Origin of angina pectoris in patients with high-grade single-vessel coronary
      artery stenosis undergoing percutaneous transluminal coronary angioplasty.
AB  - This study shows that in patients with subtotal (95% to 99%) coronary artery
      stenosis, the presence of myocardial ischemia is dictated primarily by the
      presence and degree of coronary collateral flow, with anterograde flow
      participating little, if at all, in the origin of myocardial ischemia and angina
      pectoris. Conversely, in patients with severe but not subtotal coronary artery
      stenosis (70% to 94%), both reduced anterograde flow and coronary
      collateralization contribute to the evolution of myocardial ischemia and angina
      pectoris.

PMID- 9631974
TI  - Significance of angiographic coronary dissection after cutting balloon
      angioplasty.
AB  - We studied 2 groups of patients with (n = 14) and without (n = 42) minor coronary
      dissections following cutting balloon angioplasty. Patients with a minor
      dissection had a longer length of lesion, higher percentage of stenosis, and
      greater acute gain after angioplasty; at 6-month follow-up both groups had a
      similar net gain and restenosis rate, suggesting that minor dissection after
      cutting balloon angioplasty has no influence on restenosis.

PMID- 9631975
TI  - Serum cholesterol levels are underevaluated and undertreated.
AB  - We reviewed data from 147 patients followed at a Veterans Administration hospital
      regarding management of hypercholesterolemia. Less than one half of patients with
      lipid analysis who met Adult Treatment Panel II/National Education Cholesterol
      Program guideline criteria for initiation of medical therapy received lipid
      lowering agents in 1 year of follow-up.

PMID- 9631976
TI  - Exercise echocardiography in children with Kawasaki disease: ventricular long
      axis is selectively abnormal.
AB  - In asymptomatic children with Kawasaki disease, left ventricular traditional
      markers of systolic and diastolic function are maintained. However, long-axis
      function, which represents the subendocardium, is abnormal during stress,
      particularly in patients with versus without coronary aneurysm.

PMID- 9631977
TI  - Indications for implantation of a dual-chamber pacemaker combined with an
      implantable cardioverter-defibrillator.
AB  - Of 122 patients with single-chamber implantable cardioverter-defibrillators
      (ICDs) reviewed retrospectively, 35 had traditional indications, 14 had other
      indications, and 18 had ICD-specific indications for dual-chamber pacing therapy.
      Thus, 67 patients (55%) were potential candidates for dual-chamber pacing, which
      has only recently become available combined with ICD therapy.

PMID- 9631978
TI  - Efficacy of low-dose combination of bisoprolol/hydrochlorothiazide compared with
      amlodipine and enalapril in men and women with essential hypertension.
AB  - The efficacy of the low-dose combination of bisoprolol/hydrochlorothiazide was
      compared with amlodipine and enalapril. The low-dose combination was found to be
      at least as effective as amlodipine and more effective than enalapril in both men
      and women.

PMID- 9631979
TI  - Beta-blocker therapy of severe congestive heart failure in infants with left to
      right shunts.
AB  - We report on the clinical and neurohumoral effects of adding low-dose propranolol
      to conventional therapy with digoxin and diuretics in 6 infants with severe
      congestive heart failure due to large left-to-right shunts. A significant
      decrease in heart failure scores and a decrease of the highly activated renin
      angiotensin-1 aldosterone system by approximately 70% strongly suggests a
      beneficial effect of this new therapeutic approach.

PMID- 9631980
TI  - Effect of benazepril on complex ventricular arrhythmias in older patients with
      congestive heart failure, prior myocardial infarction, and normal left
      ventricular ejection fraction.
AB  - Sixty patients, mean age 82 +/- 8 years, with congestive heart failure, prior
      myocardial infarction, normal left ventricular ejection fraction, and > or = 30
      ventricular premature complexes per hour detected by 24-hour ambulatory
      electrocardiograms, and who were treated with diuretics, were randomized to
      treatment with benazepril 20 to 40 mg/day (30 patients) or to no benazepril (30
      patients). At a median of 6 months after treatment, follow-up 24-hour ambulatory
      electrocardiograms showed that compared with no benazepril, benazepril caused no
      significant reduction in the number of ventricular premature complexes per hour
      or in the number of runs of ventricular tachycardia per 24 hours.

PMID- 9631981
TI  - Effects of maximally tolerated oral therapy on the six-minute walking test in
      patients with chronic congestive heart failure secondary to either ischemic or
      idiopathic dilated cardiomyopathy.
AB  - In patients with heart failure, therapy with "maximally tolerated" oral doses of
      diuretics, vasodilators, and digitalis results in a significant increase in the
      distance walked during the 6-minute walking test, compared with conventional
      therapy at "standard" doses, indicating an improvement in exercise tolerance. The
      6-minute walk test is a simple, inexpensive, and well-tolerated test to measure
      changes in exercise tolerance induced by pharmacologic interventions, even on a
      short-term basis.

PMID- 9631982
TI  - Electrical connection of native and transplanted sinus nodes via atrial to atrial
      pacing improves exercise performance after cardiac transplantation.
AB  - Chronotropic incompetence limits exercise performance in cardiac transplant
      patients. Electrical linkage of the innervated native sinus node and the
      denervated donor atrium or direct donor atrium pacing improves exercise
      performance in patients early after transplant.

PMID- 9631983
TI  - Right ventricular function and exercise performance late after primary repair of
      tetralogy of Fallot with the transannular patch in infancy.
AB  - To evaluate the late effects of chronic pulmonary regurgitation against the
      putative benefits from the current surgical trend of primary repair of tetralogy
      of Fallot with a transannular patch in infancy, 10 patients > 10 years after
      early primary repair and 7 matched normal controls underwent exercise stress test
      and cine magnetic resonance imaging assessment of ventricular functions. Right
      ventricular impaired diastolic function and decreased exercise capacity, both
      significantly associated with pulmonary regurgitation in patients, indicated that
      early primary repair of tetralogy may not prevent late ventricular dysfunction
      and diminished exercise performance if chronic regurgitation results from right
      ventricular outflow tract reconstruction.

PMID- 9631984
TI  - Caffeine abstinence augments the systolic blood pressure response to adenosine in
      humans.
AB  - Blood pressure and heart rate responses to adenosine infusion (35, 70, and 140
      microg/kg/min, intravenously) were studied in 7 healthy men after 6, 30, 78, 150,
      and 318 hours of abstinence from regular caffeine use. The finding that caffeine
      abstinence augmented the systolic pressor response (from -1 +/- 2 mm Hg at 6
      hours to +9 +/- 2 mm Hg at 318 hours; p = 0.01) but not the tachycardic response
      to adenosine has implications for current clinical and research applications of
      this purine.

PMID- 9631985
TI  - Hemodynamic basis of mitral E transmission in the left ventricular cavity and its
      relation to the left ventricular relaxation process.
AB  - Mitral E-wave transit time to the left ventricular outflow tract was measured as
      an E-Er interval in 30 subjects undergoing cardiac catheterization. The E-Er
      interval (range 30 to 190 ms) correlated with left ventricular peak negative
      dP/dt (r = -0.62, p = 0.0003) and tau (r = 0.74, p <0.0001) but not with left
      ventricular minimum, pre-A-wave, or end-diastolic pressures. We conclude that the
      E-Er interval is an easily obtainable Doppler measurement that reflects the left
      ventricular relaxation process.

PMID- 9631986
TI  - Percutaneous coil occlusion of ascending aorta to pulmonary artery shunts.
AB  - Two patients with pulmonary atresia and intact ventricular septum each underwent
      early palliative surgery with a pulmonary valvotomy and an ascending aorta to
      pulmonary artery shunt. Adequate right ventricular growth and relief of pulmonary
      stenosis rendered the shunts unnecessary. The shunts were successfully occluded
      percutaneously with Gianturco coils.

PMID- 9631987
TI  - An episode of ventricular tachycardia during long-duration spaceflight.
AB  - An episode of nonsustained ventricular tachycardia was recorded from a crew
      member during the second month aboard the MIR space station. Although
      asymptomatic, this cardiac event increases the concern that serious cardiac
      dysrhythmias may be a limiting factor during long-duration spaceflight.

PMID- 9631988
TI  - Once-weekly fluconazole in the treatment of onychomycosis: introduction.

PMID- 9631989
TI  - Once-weekly fluconazole (150, 300, or 450 mg) in the treatment of distal
      subungual onychomycosis of the toenail.
AB  - BACKGROUND: Onychomycosis is a prevalent infection of the nail caused primarily
      by dermatophytes. Fluconazole is active in vitro against the most common
      pathogens of onychomycosis, penetrates into the nail bed, and is clinically
      effective in the treatment of a wide variety of superficial fungal infections.
      OBJECTIVE: The purpose of this study was to compare the efficacy and safety of
      three different doses of fluconazole (150, 300, and 450 mg) given orally once
      weekly to that of placebo in the treatment of distal subungual onychomycosis of
      the toenail caused by dermatophytes. METHODS: In this multicenter, double-blind
      study, 362 patients with mycologically confirmed onychomycosis were randomized to
      treatment with fluconazole, 150, 300, or 450 mg once weekly, or placebo once
      weekly for a maximum of 12 months. To enter the study, patients were required to
      have at least 25% involvement of the target nail with at least 2 mm of healthy
      nail from the nail fold to the proximal onychomycotic border. Patients who were
      clinically cured or improved at the end of treatment were further evaluated over
      a 6 month follow-up period. At both the end of therapy and the end of follow-up,
      clinical success of the target nail was defined as reduction of the affected area
      to less than 25% or cure. RESULTS: At the end of therapy, 86% to 89% of patients
      in the fluconazole treatment groups were judged clinical successes as defined
      above compared with 8% of placebo-treated patients. Clinical cure (completely
      healthy nail) was achieved in 28% to 36% of fluconazole-treated patients compared
      with 3% of placebo-treated patients. Fluconazole demonstrated mycologic
      eradication rates of 47% to 62% at the end of therapy compared with 14% for
      placebo. The rates at the end of follow-up were very similar, indicating that
      eradication of the dermatophyte was maintained over the 6-month period. All
      efficacy measures for the fluconazole groups were significantly superior to
      placebo (p=0.0001); there were no significant differences between the fluconazole
      groups on these efficacy measures. The clinical relapse rate among cured patients
      over 6 months of follow-up was low at 4%. Fluconazole was well tolerated at all
      doses over the 12-month treatment period, with the incidence and severity of
      adverse events being similar between the fluconazole and placebo treatment
      groups. Mean time to clinical success in the fluconazole treatment groups was 6
      to 7 months. This time frame may be used as a guideline for fluconazole treatment
      duration. CONCLUSION: The results of this study support the use of fluconazole in
      the treatment of distal subungual onychomycosis of the toenail caused by
      dermatophytes. Doses between 150 to 450 mg weekly for 6 months were clinically
      and mycologically effective as well as safe and well tolerated.

PMID- 9631990
TI  - Once-weekly fluconazole (150, 300, or 450 mg) in the treatment of distal
      subungual onychomycosis of the fingernail.
AB  - BACKGROUND: Onychomycosis is a prevalent infection of the nail caused primarily
      by dermatophytes. Fluconazole is active in vitro against the most common
      pathogens, penetrates into the nail bed, and is clinically effective in the
      treatment of a wide variety of fungal infections. OBJECTIVE: The purpose of this
      study was to assess the safety and efficacy of oral fluconazole 150, 300, and 450
      mg administered once weekly compared with placebo in the treatment of distal
      subungual onychomycosis of the fingernail caused by dermatophytes. METHODS: This
      was a multicenter, randomized, double-blind, placebo-controlled study enrolling
      349 patients with onychomycosis of the fingernails. Clinical and mycologic
      efficacy as well as measures of safety were assessed monthly for a maximum of 9
      months of treatment, with additional safety visits occurring at weeks 2 and 6.
      For inclusion, patients were required to have clinically and mycologically
      documented onychomycosis of the fingernail caused by dermatophytes with at least
      25% involvement of the target fingernail. After end of therapy, patients with
      improved or cured fingernails entered a blinded 6-month follow-up without drug
      treatment during which efficacy was assessed every 2 months. Efficacy was
      assessed by clinical (visual) and mycologic (microscopic and culture) measures.
      Clinical measures included assessments of the percentage of target nail
      involvement, measurement of the distance from the nail fold to the proximal
      onychomycotic border, and signs and symptoms of onychomycosis. RESULTS:
      Fluconazole was significantly superior to placebo in eradicating clinical and
      mycologic symptoms of onychomycosis, both at the end of active treatment and at 6
      months after treatment (p=0.0001 for all efficacy measures). At the end of
      therapy, 91% to 100% of patients in the fluconazole groups were judged clinical
      successes, defined as reduction of the affected area of the target nail to less
      than 25% or cure, compared with 8% for placebo. Clinical cure rates at end of
      therapy were 76%, 85%, and 90% for fluconazole 150, 300, and 450 mg,
      respectively, compared with 3% for placebo. These clinical success and cure rates
      were largely maintained or improved during follow-up. Clinical relapse in cured
      patients during the follow-up period was very low (1.5% to 3.3%). Fluconazole
      demonstrated mycologic eradication rates of 89% to 100% at the end of treatment
      and 90% to 99% at the end of follow-up; for placebo the rates were 8% and 12%,
      respectively. CONCLUSION: Fluconazole administered once weekly is safe and
      effective in eradicating distal subungual onychomycosis of the fingernail caused
      by dermatophytes.

PMID- 9631991
TI  - Once-weekly fluconazole (450 mg) for 4, 6, or 9 months of treatment for distal
      subungual onychomycosis of the toenail.
AB  - BACKGROUND: Fluconazole is a bis-triazole antifungal agent approved for the
      treatment of oropharyngeal, esophageal, and vaginal candidiasis, serious systemic
      candidal infections, and cryptococcal meningitis. OBJECTIVE: The purpose of this
      study was to evaluate three different durations of once-weekly fluconazole for
      the treatment of onychomycosis of the toenail caused by dermatophytes. METHODS:
      In a multicenter, randomized, double-blind, parallel, placebo-controlled trial,
      384 patients with distal subungual onychomycosis of the toenail received
      fluconazole, 450 mg once weekly, or placebo for 4, 6, or 9 months. For inclusion,
      patients were required to have mycologically confirmed distal subungual
      onychomycosis of the toenail with a large toenail at least 25% clinically
      affected but having at least 2 mm of healthy nail between the nail fold and the
      proximal onychomycotic border. Efficacy was assessed by clinical and mycologic
      (microscopic and microbiologic) measures at screening, at every treatment visit
      starting at month 3, and at months 2, 4, and 6 after therapy. Observed or
      volunteered adverse events were recorded and classified at all visits. RESULTS:
      At the end of treatment, very significantly superior clinical and mycologic
      results were achieved in all fluconazole groups compared with placebo (p=0.0001).
      This superiority was largely maintained over 6 months of follow-up. The clinical
      and mycologic responses of the 9-month treatment duration were significantly
      superior to the 4- and 6-month durations. Similar percentages of patients in the
      fluconazole and placebo groups reported adverse experiences for all three
      durations of the study. CONCLUSION: Results of this study support the efficacy
      and safety of fluconazole in the treatment of distal subungual onychomycosis of
      the toenail.

PMID- 9631992
TI  - Pharmacokinetics of three doses of once-weekly fluconazole (150, 300, and 450 mg)
      in distal subungual onychomycosis of the toenail.
AB  - BACKGROUND: Preliminary clinical data suggest that fluconazole is effective in
      the treatment of patients with onychomycosis. To design optimum dosage regimens,
      a better understanding of fluconazole's distribution into and elimination from
      nails is needed. OBJECTIVE: The purpose of this study was to determine plasma and
      toenail concentrations of fluconazole. METHODS: In this multicenter, randomized,
      double-blind investigation, fluconazole (150 mg, 300 mg, or 450 mg) or matching
      placebo was administered once a week for a maximum of 12 months to patients with
      onychomycosis of the toenail. A total of 151 subjects participated in the
      pharmacokinetic assessment. Blood samples and distal toenail clippings from both
      affected and healthy nails were obtained for fluconazole concentration
      determinations at baseline, at the 2-week visit, at each monthly visit until the
      end of treatment, and then at 2, 4, and 6 months (nail samples only at the latter
      two) after fluconazole was discontinued. RESULTS: Fluconazole was detected in
      healthy and affected nails at the 2-week assessment in nearly all subjects. The
      median time to reach steady-state fluconazole concentrations in healthy nails was
      4 to 5 months in the three fluconazole dose groups. In affected nails, steady
      state fluconazole concentrations were achieved more slowly, with a median time of
      6 to 7 months. At the 8-month assessment, affected toenail fluconazole
      concentrations were higher than corresponding plasma fluconazole concentrations,
      with ratios of 1.31 to 1.50 in the three active treatment groups. Toenail
      concentrations of fluconazole declined slowly after treatment was discontinued,
      with elimination half-lives of 2.5, 2.4, and 3.7 months for the 150, 300, and 450
      mg doses, respectively. Measurable fluconazole concentrations were still present
      in toenails at 6 months after treatment in most subjects. CONCLUSION: Fluconazole
      penetrates healthy and diseased nails rapidly, yielding detectable concentrations
      after two weekly doses. Once it penetrates nail, fluconazole persists for up to 6
      months or longer after therapy is stopped. These favorable pharmacokinetic
      characteristics support a once-weekly fluconazole dosage regimen for the
      treatment of patients with onychomycosis.

PMID- 9631993
TI  - Pharmacokinetics of three once-weekly dosages of fluconazole (150, 300, or 450
      mg) in distal subungual onychomycosis of the fingernail.
AB  - BACKGROUND: Fluconazole has proven to be safe and effective for a variety of
      superficial and systemic fungal infections. Preliminary analysis of extensive
      Phase III studies suggests that it is very effective for the treatment of
      onychomycosis. Its pharmacokinetic properties, including low molecular weight and
      high water-solubility, suggest a unique ability to penetrate the nail. This
      feature is likely to account in part for fluconazole's effectiveness in the
      treatment of onychomycosis. OBJECTIVE: Determinations of plasma and fingernail
      concentrations of fluconazole were performed as part of a larger study comparing
      the safety and efficacy of once-weekly fluconazole (150, 300, and 450 mg) to
      placebo in the treatment of distal subungual onychomycosis of the fingernails
      caused by dermatophytes. The relationship between fluconazole concentrations and
      efficacy was also examined. METHODS: Pharmacokinetic studies were performed by
      means of plasma and fingernail samples from 133 patients, a subset of 349
      patients participating in a double-blind, placebo-controlled clinical trial of
      fluconazole administered in once-weekly doses of 150, 300, or 450 mg until cure
      of onychomycosis or for a maximum of 9 months. Blood and fingernail samples for
      pharmacokinetic analysis were taken at baseline, at week 2, and at monthly
      intervals during the treatment phase of the study. Patients considered clinically
      cured or improved also participated in a 6-month follow-up study. During this
      phase, patients were monitored and samples taken every 2 months. RESULTS:
      Significant amounts of fluconazole were detected in the earliest fingernail
      samples taken (after 2 weeks of treatment). After two weekly doses, 30% to 33% of
      steady-state concentrations had been achieved in healthy nails and 22% to 29% in
      affected nails. Steady state was achieved in 3 to 5 months. Fluconazole
      concentration in nails as well as plasma followed dose-proportional
      pharmacokinetics. Nail:plasma ratios in affected nails were 0.4 to 0.6 at 2 weeks
      and 1.7 to 1.8 at 6 months. Fluconazole concentrations fell slowly after drug
      discontinuation and were still detectable 4 months after end of treatment. A
      statistically significant correlation was found between steady-state
      concentration and clinical and global outcomes. CONCLUSION: Fluconazole rapidly
      penetrates the fingernail, where it is retained at detectable levels for at least
      4 months after drug discontinuation. A significant correlation exists between
      fluconazole concentration in the fingernails and clinical and global outcomes.

PMID- 9631994
TI  - Cutaneous pseudolymphomas.
AB  - Cutaneous pseudolymphoma refers to a heterogeneous group of benign reactive T- or
      B-cell lymphoproliferative processes of diverse causes that simulate cutaneous
      lymphomas clinically and/or histologically. The inflammatory infiltrate is
      bandlike, nodular, or diffuse and is composed predominantly of lymphocytes with
      or without other inflammatory cells. Depending on the predominant cell type in
      the infiltrate, cutaneous pseudolymphomas are divided into T- and B-cell
      pseudolymphomas. Cutaneous T-cell pseudolymphomas include idiopathic cutaneous T
      cell pseudolymphoma, lymphomatoid drug reactions, lymphomatoid contact
      dermatitis, persistent nodular arthropod-bite reactions, nodular scabies, actinic
      reticuloid, and lymphomatoid papulosis. Cutaneous B-cell pseudolymphomas include
      idiopathic lymphocytoma cutis, borrelial lymphocytoma cutis, tattoo-induced
      lymphocytoma cutis, post-zoster scar lymphocytoma cutis, and some persistent
      nodular arthropod-bite reactions. This review attempts to discuss current aspects
      of the classification, pathogenesis, clinical spectrum, histopathologic and
      immunohistochemical diagnosis, and laboratory investigations for clonality in the
      various types of cutaneous pseudolymphomas.

PMID- 9631995
TI  - Clinicopathologic correlation of hypocomplementemic and normocomplementemic
      urticarial vasculitis.
AB  - BACKGROUND: Urticarial vasculitis is characterized by persistent urticarial
      lesions with histologic evidence of leukocytoclastic vasculitis.
      Hypocomplementemic urticarial vasculitis (HUV) is a distinct clinical entity in a
      subset of patients with urticarial vasculitis. OBJECTIVE: We examined
      presentation of urticarial vasculitis and factors predictive of connective tissue
      disease. METHODS: The clinical, histologic, and immunologic characteristics of
      132 patients with urticarial vasculitis seen at the Mayo Clinic were examined,
      and features of the hypocomplementemic patients were compared with those of the
      normocomplementemic patients. RESULTS: Twenty-four patients (18%) had
      hypocomplementemia; all were female. Interstitial dermal neutrophilia was seen in
      19 biopsy specimens (83%). On direct immunofluorescence (DIF) testing of lesional
      skin, 23 patients (96%) had a continuous strong granular deposition of
      immunoreactants along the basement membrane zone compatible with lupus
      erythematosus in addition to vascular fluorescence. Systemic lupus erythematosus
      (SLE) was present or occurred in 13 (54%). One hundred eight patients (82%) had
      normocomplementemia; 65 (60%) were female. Interstitial dermal neutrophilia was
      seen in 11 of 26 (42%) randomly selected biopsy specimens. On DIF, one patient
      (1%) had the lupus band. SLE occurred in three patients (3%). CONCLUSION:
      Patients with HUV were more likely to be female, to have diffuse neutrophilia on
      biopsy specimens stained with hematoxylin and eosin, to have continuous strong
      granular deposition of immunoreactants along the basement membrane zone on DIF,
      and to have SLE than normocomplementemic patients. We submit that HUV represents
      a subset of SLE with shared clinical, laboratory, and immunologic features.

PMID- 9631996
TI  - Basal cell carcinoma with ossification.
AB  - BACKGROUND: Osteoma cutis, the presence of lamellar bone in the skin, is
      relatively common. This process is divided into two categories: primary osteoma
      cutis and secondary osteoma cutis. OBJECTIVE: The purpose of this study was to
      describe the clinical and histopathologic features of patients in whom lamellar
      bone developed in cutaneous basal cell carcinoma. METHODS: We evaluated the
      features of five cases of osteoma cutis associated with basal cell carcinoma and
      obtained detailed clinical information from those patients. RESULTS: All five
      patients had significant underlying medical conditions, including two patients
      who were receiving interferon alfa-2b therapy. Three patients had been previously
      treated with electrodesiccation and curettage. The amount of sun exposure
      experienced by these patients varied. Histologically, the basal cell carcinomas
      were of the nodular or micronodular variety. Bone was found both in the stroma
      and intratumorally. CONCLUSION: The presence of bone within basal cell carcinomas
      is not uncommon and may be more prevalent in patients with an underlying medical
      disorder.

PMID- 9631997
TI  - North American Contact Dermatitis Group patch test results for the detection of
      delayed-type hypersensitivity to topical allergens.
AB  - BACKGROUND: Allergic contact dermatitis is a significant cause of cutaneous
      disease affecting many individuals. Patch testing, when used properly, often
      provides support for the diagnosis of allergic contact dermatitis. OBJECTIVE:
      This article reports patch testing results from July 1, 1994, to June 30, 1996,
      by the North American Contact Dermatitis Group (NACDG). METHODS: Patients
      evaluated in our patch test clinics were tested with the same screening series of
      allergens by the use of a standardized patch testing technique. The data from
      these patients were recorded on a standard computer entry form and analyzed.
      RESULTS: Forty-nine allergens were tested on 3120 patients. Budesonide was added
      to the series in July 1995 and tested on 1678 patients. Of these patients, 66.5%
      had positive allergic patch test reactions, and 57% had at least one allergic
      reaction that was felt to be clinically relevant to the present or past
      dermatitis. The 20 screening allergens commercially available to United States
      dermatologists in the Allergen Patch Test Kit, accounted for only 54.1% of the
      patients with positive allergic reactions. The additional 30 allergens on the
      NACDG screening series accounted for 47% of patients with positive allergic
      reactions. Had the Allergen Patch Test Kit alone been used, 12.4% of all patients
      tested may have had their disease misclassified as a nonallergic disorder, and an
      additional 34.4% of all tested patients would not have had their allergies fully
      defined. Among those patients with positive responses to the supplemental
      allergens, 81% of the responses were of present or past relevance. The 12 most
      frequent contact allergens were nickel sulfate, fragrance mix, thimerosal,
      quaternium-15, neomycin sulfate, formaldehyde, bacitracin, thiuram mix, balsam of
      Peru, cobalt chloride, para-phenylenediamine, and carba mix. The present
      relevance varied with the specific allergen from 10.7% (thimerosal) to 85.7%
      (quaternium-15). Among newer allergens,
      methyldibromoglutaronitrile/phenoxyethanol (cosmetic preservative) caused
      positive allergic reactions in 2% of the patients; tixocortol-21-pivalate and
      budesonide (corticosteroids), in 2.0% and 1.1% of the patients, respectively; and
      ethylene urea/melamine formaldehyde mix (textile resin), in 5% of the patients.
      CONCLUSION: The usefulness of patch testing is enhanced with the number of
      allergens tested, because allergens not found on the commercially available
      screening series in the United States frequently give relevant allergic
      reactions.

PMID- 9631998
TI  - Familial eosinophilic cellulitis, dysmorphic habitus, and mental retardation.
AB  - BACKGROUND: Eosinophilic cellulitis is a polymorphous, chronic disease
      characterized by eosinophil infiltration and granulomatous inflammation.
      OBJECTIVE: Our purpose was to describe the clinical, histologic, and
      immunohistologic findings in three family members who have had eosinophilic
      cellulitis since childhood associated with mental retardation and abnormal body
      habitus. METHODS: Family members were evaluated. Multiple skin biopsy specimens
      were obtained and examined after hematoxylin-and-eosin staining, by
      immunofluorescence and by electron microscopy. Blood specimens were analyzed by
      immunoassays for eosinophil granule proteins and eosinophil active cytokines.
      RESULTS: Three short-statured, mentally retarded family members with abnormal
      body habitus in at least two generations had recurrent eosinophilic cellulitis.
      Peripheral blood and bone marrow eosinophilia was present. Plasma eosinophil
      granule major basic protein and eosinophil-derived neurotoxin levels were
      elevated with normal plasma eosinophil cationic protein levels. Eosinophil
      survival in culture was increased by patients' plasma and was blocked with
      monoclonal interleukin-5 antibody. The level of plasma interleukin-5 was
      elevated. Lesional skin biopsy specimens showed massive staining for three
      eosinophil granule proteins. Electron microscopy showed eosinophil disruption.
      CONCLUSION: Eosinophilic cellulitis, mental retardation, and abnormal body
      habitus were likely inherited as a dominant syndrome in this family in which
      eosinophil involvement was striking.

PMID- 9631999
TI  - Papular dermatitis (subacute prurigo, "itchy red bump" disease): pilot study of
      phototherapy.
AB  - BACKGROUND: Some patients with a subacute or chronic pruritic erythematous
      papular eruption are refractory to treatment. We previously described a number of
      these patients with papular dermatitis or subacute prurigo. OBJECTIVE: The
      purpose of this study was to examine the effectiveness of different types of
      phototherapy for treatment of papular dermatitis. METHODS: We reviewed the
      medical records of 11 patients who were diagnosed with papular dermatitis and who
      underwent phototherapy within the last 5 years. RESULTS: Eleven patients had a
      total of 17 phototherapy courses: psoralen-UVA (PUVA; 9), UVA/UVB light (3), and
      UVB alone (5). Within the PUVA treatment group, three of nine patients
      experienced total clearing, and six of nine patients experienced partial
      improvement. Although patients in all groups relapsed with time, overall the PUVA
      treated patients had the best response rate and the best chance of the condition
      remaining clear after treatment was stopped. CONCLUSION: PUVA may be an effective
      treatment for papular dermatitis. The frequency of relapse indicates that
      maintenance treatments may be necessary for long-term control of the disease.

PMID- 9632000
TI  - Methyldibromoglutaronitrile (Euxyl K400): a new and important sensitizer in the
      United States?
AB  - BACKGROUND: Methyldibromoglutaronitrile (MDGN) is a component of Euxyl K400, a
      preservative used in many skin care products in Europe. MDGN has been used in
      skin care products in the United States for the last 5 years. Contact allergy
      from MDGN has been reported from Europe. OBJECTIVE: The purpose of this study was
      to determine the frequency of MDGN as a sensitizer in patients undergoing routine
      patch testing. METHODS: We reviewed the results in 163 patients who underwent
      patch testing during a 4-month period to determine the number who had any
      reaction to MDGN at two different concentrations (0.2% and 0.5%). Tests were
      graded with the use of the North American Contact Dermatitis Group criteria (0 to
      3+), and readings were performed at 48 and 96 hours (all positive reactions were
      evaluated at a follow-up visit or by telephone interview). RESULTS: In the 4
      month period, 45 of the 163 patients showed some reaction (+/- to 3+) at one or
      more readings. Of these, the results for 23 patients were considered to be
      irritant false-positive reactions; for 3 patients, the results were classified as
      uncertain; and for 19 patients, the results were classified as allergic. Of
      these, the results for eight patients were of definite relevance; the results for
      five patients were of probable relevance, and the results for six patients were
      of doubtful relevance to the problem condition. Other positive patch tests to a
      variety of allergens were frequently seen in persons positive to MDGN.
      CONCLUSION: MDGN is a sensitizer in skin products and, with the increase of its
      use, should be considered in the patch test evaluation of patients with
      persistent dermatitis. Optimum patch test concentrations are yet to be
      determined.

PMID- 9632001
TI  - Administration of DAB389IL-2 to patients with recalcitrant psoriasis: a double
      blind, phase II multicenter trial.
AB  - BACKGROUND: Current therapies for recalcitrant psoriasis focus on
      immunoregulation and targeting of activated T-lymphocytes rather than
      keratinocytes. Previous studies with low doses of the lymphocyte-selective fusion
      protein DAB389IL-2 have shown benefit to patients with psoriasis. OBJECTIVE: We
      examined the safety and efficacy of DAB389IL-2 in 41 volunteers receiving more
      frequent and higher doses than in a previous trial. METHODS: Patients were
      randomized to receive either placebo or 5, 10, or 15 microg/kg daily of DAB389IL
      2 intravenously for 3 consecutive days each week for 4 consecutive weeks with a
      subsequent 4-week observation period. RESULTS: Of the placebo group, 17% (2 of
      12) exhibited at least 50% improvement from baseline Psoriasis Area and Severity
      Index scores at the end of the study, whereas 24% of all treated patients (7 of
      29) showed the same improvement. Overall, 3 of 12 (25%) patients given placebo as
      opposed to 12 of 29 (41%) patients treated with DAB389IL-2 improved to this same
      extent at some point during the study. The rate of improvement for treated
      patients was significantly greater than for placebo patients (p = 0.04; repeated
      measures ANOVA). Among treated patients, decreases in Psoriasis Area and Severity
      Index scores were paralleled by changes in the Physician's Global Assessment and
      the Dermatology Life Quality Index. Treatment in ten patients was discontinued
      because of adverse events. Flu-like symptoms were the most common with severity
      increasing at the two higher doses. Only one serious adverse event was reported.
      This occurred in a patient receiving 5 microg/kg daily who experienced vasospasm
      and a coagulopathy resulting in arterial thrombosis. CONCLUSION: Our findings are
      consistent with the potential antipsoriatic activity of DAB389IL-2 demonstrated
      in an earlier study. However, DAB389IL-2 was less well tolerated at this dosing
      regimen, particularly at the highest dose, and it was too toxic at these doses
      and schedules to be considered in the routine treatment of psoriasis.

PMID- 9632002
TI  - Sparfloxacin-induced photosensitivity and the occurrence of a lichenoid tissue
      reaction after prolonged exposure.
AB  - BACKGROUND: A new antibacterial quinolone, sparfloxacin (SPFX), frequently causes
      photosensitive dermatitis and sometimes induces a treatment-resistant lichenoid
      tissue reaction (LTR). OBJECTIVE: We attempted to determine the factors that
      induce LTR in SPFX-induced photodermatitis. METHODS: Thirteen patients with SPFX
      photosensitive dermatitis were studied clinically and histopathologically.
      RESULTS: Six of the 13 patients had acute dermatitis with epidermal spongiosis
      and focal epidermal HLA-DR and intercellular adhesion molecule-1 (ICAM-1)
      expression with CD4+ cell infiltration. The other seven displayed LTR with basal
      cell liquefaction degeneration and diffuse epidermal HLA-DR and ICAM-1 expression
      associated with CD8+ cells. The seven patients with LTR were exposed to UV and
      SPFX for more than 2 weeks after the appearance of their initial eruption,
      whereas the six patients with acute dermatitis were treated within 2 weeks. The
      acute dermatitis lesions cleared significantly within 2 weeks, but the LTR
      lesions persisted for more than 6 weeks. CONCLUSION: Patients with quinolone
      induced photosensitivity should be treated within 2 weeks of onset to prevent
      LTR.

PMID- 9632003
TI  - Analysis of vascularity of human neurofibromas.
AB  - BACKGROUND: A common misperception is that the vascularity of a tumor can be
      determined by its gross appearance. Neurofibromas are grossly white in
      appearance. The degree of vascularity of neurofibromas has not been determined.
      OBJECTIVE: The purpose of this study was to determine the extent of
      neovascularization of neurofibromas. METHODS: Neurofibromas from patients with
      neurofibromatosis-1 or spontaneous neurofibromas were stained with antibodies
      against von Willebrand factor (factor VIII-related antigen) and vascular
      endothelial growth factor (VEGF). RESULTS: Neurofibromas, both spontaneous and
      congenital, exhibit a high degree of vascularity. In addition, perivascular cells
      in neurofibromas stain with antibodies to VEGF, an angiogenic factor. CONCLUSION:
      Neurofibromas, despite their gross appearance, are highly vascular. Their
      vascularity may be mediated, in part, through the angiogenic factor VEGF.

PMID- 9632004
TI  - Efficacy of pentoxifylline in the treatment of pruritic papular eruption of HIV
      infected persons.
AB  - BACKGROUND: Pruritic papular eruption (PPE) of HIV/AIDS is a common manifestation
      of HIV infection. Unfortunately, treatments for the unremitting pruritus have
      yielded only partial relief. OBJECTIVE: Our purpose was to assess the clinical
      efficacy of pentoxifylline in the treatment of pruritus in HIV-infected patients
      with PPE while measuring its effects on HIV viral load and levels of serum
      triglycerides, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-4.
      METHODS: Eleven of the 12 patients with PPE and HIV infection placed on a regimen
      of oral pentoxifylline completed the 8-week study. The degree of pruritus both
      before and after therapy was measured by means of a patient-reported visual
      analog scale (0 = none and 10 = worst experienced). A global assessment of the
      number and size of PPE lesions was performed by the investigator, and serum TNF
      alpha, IL-4, and triglyceride levels, as well as HIV viral load, were measured.
      RESULTS: The average degree of pruritus was significantly reduced (p = 0.0009)
      from 6.5 at baseline examination to 3.6 at the end of the study. Ten of 11
      patients experienced a reduction in their pruritus, ranging from 22.6% to 87.3%.
      The global assessment of PPE lesions decreased from baseline in most patients and
      increased slightly in one patient. Serum TNF-alpha was detectable in one patient
      at baseline, but was undetectable at the end of the study period. Similarly, the
      two patients who had detectable serum IL-4 at baseline had undetectable serum IL
      4 levels at the end of the study. Triglyceride levels in six patients decreased
      an average of 23.9% by week 8. Although when compared with baseline values, HIV
      viral loads in seven patients decreased, one patient had no change, and three
      patients had an increase in their viral load at the end of the study, the
      magnitude of the changes were of little clinical importance. CONCLUSION:
      Pentoxifylline is a safe and efficacious treatment of pruritus in HIV-infected
      patients with PPE. Future controlled studies are needed to confirm the
      effectiveness of this treatment.

PMID- 9632005
TI  - Squamous cell carcinoma of the lip treated with Mohs micrographic surgery:
      outcome at 5 years.
AB  - BACKGROUND: Mohs micrographic surgery (MMS) is believed to be a highly effective
      treatment of squamous cell carcinoma (SCC) of the lip. OBJECTIVE: The goals of
      our study were to determine the long-term (5-year) outcome of patients treated
      with MMS for SCC of the lip and to identify factors associated with tumor
      recurrence. METHODS: Clinical and histopathologic data from 50 consecutive cases
      of SCC of the lip treated with MMS were retrospectively reviewed. RESULTS: There
      were no tumor-related deaths or metastases. Forty-six patients (92%) remained
      free of disease. Four patients (8%) were diagnosed with SCC at the surgical site
      after MMS. Recurrent lesions tended to be superficial and occurred in the setting
      of severe actinic cheilitis. The average time to diagnosis after MMS was 2.5
      years. All patients with recurrent disease were treated with further MMS and had
      successful results. No recurrences were seen among patients who received adjuvant
      treatment for actinic cheilitis with the carbon dioxide (CO2) laser, had clinical
      lesions 1 cm or less in diameter, or had post-MMS defects 2 cm or less in
      diameter. CONCLUSION: MMS is highly effective for treating both primary and
      recurrent SCC of the lip. Treatment of coexisting actinic cheilitis may lower the
      risk for local recurrence after MMS.

PMID- 9632006
TI  - Asteroid bodies and other cytoplasmic inclusions in necrobiotic xanthogranuloma
      with paraproteinemia.
AB  - BACKGROUND: Necrobiotic xanthogranuloma (NXG) with paraproteinemia is a
      distinctive palisading granuloma of the skin. Extracutaneous lesions are rarely
      present. OBJECTIVE: The purpose of this study was to confirm the presence and
      significance of giant cell asteroid bodies and other cytoplasmic inclusions in
      NXG with paraproteinemia. METHODS: Skin biopsy specimens from 24 patients with
      NXG with paraproteinemia were reviewed; autopsy and lung biopsy specimens from
      two patients were stained for iron, calcium, and polysaccharide. RESULTS: Giant
      cell asteroid bodies were observed in skin biopsy specimens of 8 (33%) of the 24
      patients. In addition, large acidophilic polygonal cytoplasmic inclusions were
      observed in myocardial tissue of one of the autopsy cases. Iron and calcium were
      not found. CONCLUSION: Asteroid bodies and other inclusions can be present in the
      giant cells of NXG with paraproteinemia. They are as frequent as, or more
      frequent than, in other granulomatous diseases and should be considered in the
      diagnosis of NXG with paraproteinemia.

PMID- 9632007
TI  - Pigmented lesions of the conjunctiva.
AB  - A careful examination of the conjunctiva and ocular adnexa should be performed as
      part of a complete dermatologic examination. This article reviews the clinical
      presentation and classification of pigmented lesions of the conjunctiva. The
      histologic features of these conjunctival lesions are compared with those of
      pigmented lesions of the skin.

PMID- 9632009
TI  - The corroding of our core.

PMID- 9632008
TI  - An assessment of topical and oral prescription and over-the-counter treatments
      for head lice.
AB  - A plethora of head lice cases that require optimal therapeutic assessments are
      developing in elementary schools. Over-the-counter therapies continue to be the
      mainstream solution for most cases of pediculosis capitis, but the onset of
      resistant cases dictates a review of available treatment modalities. The
      increased efficacy of prescription drugs, namely topical 5% permethrin and oral
      ivermectin, underline the expanding role that physicians will serve in the
      eradication of head lice in our communities.

PMID- 9632010
TI  - Outcomes research in your office.
AB  - This article reviews the definition of outcomes research. It explores the reasons
      that outcomes research should be conducted by practicing physicians in both
      university and private practice settings. Methods for outcomes research with
      examples relevant to dermatologists are detailed.

PMID- 9632011
TI  - Surgical pearl: Repair of split or deformed ear lobe with a tongue depressor
      blade for stabilization during surgery.

PMID- 9632012
TI  - Cutaneous B-cell lymphoma associated with angioimmunoblastic lymphadenopathy.

PMID- 9632013
TI  - Male breast carcinoma with extensive metastases to the skin.

PMID- 9632014
TI  - Multiple melanoma metastases in split-thickness skin graft donor sites.

PMID- 9632015
TI  - Familial multiple acral mucinous fibrokeratomas.

PMID- 9632016
TI  - Tazarotene gel for Darier's disease.

PMID- 9632017
TI  - Treatment of primary anetoderma with colchicine.

PMID- 9632018
TI  - High-dose-rate brachytherapy with a custom-surface mold to treat recurrent
      squamous cell carcinomas of the skin of the forearm.

PMID- 9632019
TI  - A molecule of about 70 kd is the immunologic marker of chronic ulcerative
      stomatitis.

PMID- 9632020
TI  - Pachyonychia congenita type 2: keratin 17 mutation in a Japanese case.

PMID- 9632021
TI  - Compatibility of calcipotriene with other topical medications.

PMID- 9632022
TI  - The classification of psoriatic arthritis.

PMID- 9632024
TI  - Ivermectin usage for cheyletiellosis.

PMID- 9632025
TI  - Bullous eruption in a patient with systemic lupus erythematosus.

PMID- 9632026
TI  - Mite dermatitis caused by Cheyletiella blakei.

PMID- 9632027
TI  - Bioinstrumentation measurements versus clinical grading scales.

PMID- 9632028
TI  - Red lunula in systemic lupus erythematosus.

PMID- 9632029
TI  - Recognition molecules are trailblazers for axon pathways.

PMID- 9632031
TI  - Tobacco smoking and bipolar disorder.
AB  - BACKGROUND: We sought to determine whether tobacco smoking is associated with
      bipolar disorder. METHOD: This case-control study carried out in Alava, in the
      north of Spain, included patients with a DSM-III-R diagnosis of bipolar disorder
      type I (N = 51) and a representative sample of the normal population (N = 517).
      Smoking history of bipolar patients was assessed with the Fagerstrom Test for
      Nicotine Dependence and was verified by family members of the patients. RESULTS:
      The frequencies of ever smoking and current daily smoking were, respectively, 63%
      (32/51) and 51% (26/51) for the bipolar patients and 45% (235/517) and 33%
      (169/517) for the control group (respective odds ratios [ORs] and 95% confidence
      intervals [CIs] were OR = 2.0, 95% CI = 1.1 to 3.8 and OR = 2.1, 95% CI = 1.2 to
      4.0). The differences were significant (p = .03 and p = .042, respectively) for
      bipolar versus control males. Bipolar disorder (in both genders) was also
      significantly associated (OR = 4.4, 95% CI = 1.7 to 11.9, p = .0015) with heavy
      smoking (more than 1 pack per day). CONCLUSION: Despite its small sample size,
      this study suggests that smoking may be more prevalent in bipolar patients than
      in the normal population. Since most patients started to smoke before the onset
      of illness, vulnerability to bipolar illness may make subjects vulnerable to
      become tobacco smokers.

PMID- 9632030
TI  - Treatment of major depression in HIV-seropositive men. HIV Neurobehavioral
      Research Center Group.
AB  - BACKGROUND: The purpose of this randomized double-blind, placebo-controlled study
      was to compare the efficacy and safety of fluoxetine plus group psychotherapy
      versus group psychotherapy alone in HIV-seropositive men (based on 1986 CDC
      classes II, III, and IV.C.2) who had been diagnosed with major depressive
      disorder (DSM-III-R). METHOD: During a 7-week trial, patients were treated with
      fluoxetine 20-60 mg or placebo 1-3 capsules per day and were seen in weekly
      supportive group psychotherapy. In addition, subjects were rated on the 17-item
      Hamilton Rating Scale for Depression (HAM-D-17), Clinical Global Impressions
      scales for Improvement (CGI-I) and Severity of Illness (CGI-S), and the short
      version of the Beck Depression Inventory (BDI-13). Of the 47 patients enrolled in
      the study, 25 were administered fluoxetine and 22 were given placebo. RESULTS:
      Subjects who received fluoxetine began to show significantly more improvement
      than patients who received placebo on both self- and observer-rated scales by the
      end of the first week of treatment. By endpoint, patients treated with fluoxetine
      experienced greater mean changes from baseline compared with placebo-treated
      patients on the HAM-D-17 (12.1 vs. 6.6; F = 6.53, df = 1,45; p < .05) and BDI-13
      (5.9 vs. 1.2; F = 5.73, df = 1,45; p < .05), and a greater percentage of
      fluoxetine-treated patients experienced a > or = 50% in HAM-D-17 scores (64% vs.
      23%; chi2= 8.60, df = 1, p < .01). Differences were particularly apparent in
      subjects whose initial depressive episodes were rated as severe (i.e., HAM-D-17
      score > or = 24). Severely depressed patients treated with fluoxetine had an
      endpoint CGI-I of 1.4 compared with an endpoint CGI-I of 2.7 for patients treated
      with placebo (F = 6.02, df = 1,11; p < .05). Further, side effects were generally
      mild and transient. The most frequently noted effects reported by subjects
      treated with fluoxetine were nausea, dry mouth, headache, and diarrhea, in
      decreasing order of frequency. CONCLUSION: This study supports the efficacy and
      safety of fluoxetine over and above group psychotherapy for the treatment of HIV
      associated major depression.

PMID- 9632032
TI  - Dose-response efficacy of paroxetine in preventing depressive recurrences: a
      randomized, double-blind study.
AB  - BACKGROUND: The authors evaluated and compared the efficacy of 20 mg versus 40 mg
      of paroxetine in a randomized, double-blind, parallel-group study during a
      maintenance period of 28 months. METHOD: Ninety-nine inpatients with recurrent,
      unipolar depression (DSM-IV criteria) who had at least 1 depressive episode
      during the 18 months preceding the index episode were openly treated with
      paroxetine 40 mg/day. Seventy-two subjects had a stable response (Hamilton Rating
      Scale for Depression score < 8) to paroxetine treatment and remained in the
      continuation treatment as outpatients for 4 months. At the time of recovery, 68
      patients were randomly assigned to 1 of the 2 maintenance treatment groups:
      paroxetine 20 mg or paroxetine 40 mg daily. RESULTS: Sixty-seven patients
      completed the 28-month follow-up period. Seventeen (51.5%) of 33 patients in the
      20-mg paroxetine regimen had a single recurrence compared with 8 (23.5%) of 34
      subjects in the 40-mg dose regimen (chi2 = 5.56, p = .018). CONCLUSION: These
      data suggest that a full dose of paroxetine is recommended in unipolar patients
      who are at high risk for recurrent depressive episodes.

PMID- 9632033
TI  - Safety of mirtazapine in overdose.
AB  - INTRODUCTION: We report 6 confirmed cases of substantial overdose with
      mirtazapine, a new antidepressant compound, that occurred up to January 1997 in
      the United States during postmarketing surveillance or in the clinical trials.
      RESULTS: In 6 patients, the mirtazapine doses ranged from 10 to 30 times the
      maximum recommended dose, and there were no serious adverse effects of overdose.
      Two patients at special risk, a 90-year-old man and a 3-year-old child, took
      higher-than-usual doses without serious sequelae. The 4 patients who combined
      other central nervous system (CNS) depressants with mirtazapine appeared to
      experience more CNS depression. One patient who ingested 60 mg of alprazolam had
      clinically significant respiratory depression in the emergency room but recovered
      fully within 24 hours. CONCLUSION: After an overdose of substantial multiples of
      mirtazapine that exceed the maximum recommended daily dosage, the new
      antidepressant mirtazapine appears to be safe in a limited number of cases.

PMID- 9632034
TI  - Once- versus twice-daily venlafaxine therapy in major depression: a randomized,
      double-blind study.
AB  - BACKGROUND: Psychotropic drug dosing regimens are often based on the
      pharmacokinetic elimination half-life of the compound. This implies that the
      pharmacokinetic half-life of the drug may be the critical or sole determinant of
      pharmacodynamic half-life. In the present study, we examined the safety and
      efficacy of once- versus twice-daily dosing regimens of the immediate-release
      formulation of venlafaxine, a serotonin and norepinephrine reuptake site blocker
      with a short elimination half-life. METHOD: Forty-eight patients with a diagnosis
      of DSM-IV major depressive episode were randomly assigned to once-daily (N = 25)
      versus twice-daily (N = 23) venlafaxine. Venlafaxine was started at 37.5 mg daily
      with specified increments up to 225 mg daily. Efficacy was rated using the
      Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Asberg Depression
      Rating Scale (MADRS), and the Clinical Global Impressions scale (CGI). RESULTS:
      Twenty-one patients in each group completed 6 weeks of treatment. We observed a
      significant reduction in mean weekly HAM-D and MADRS scores at weeks 1 through 6
      for both dosing groups (p < .001). There were no statistically significant
      differences in mean HAM-D or MADRS scores between dosing groups at any time
      point. There was, however, a nonsignificant trend for a more rapid reduction in
      the mean HAM-D score at week 2 (p < .06) and in the mean MADRS score at week 1 (p
      < .07) and week 2 (p < .09) in the b.i.d. dosing group. Similarly, there was a
      significant decrease in the CGI score at week 2 (p < .02) in the b.i.d. dosing
      group. The rate of adverse events was similar between treatment groups; the most
      common adverse events were transient nausea and headaches. CONCLUSION: These
      results indicate that the immediate-release formulation of venlafaxine may be
      safe and effective in some patients when used in a once-daily dose regimen.
      Moreover, the present results suggest that the short elimination half-life of
      immediate-release venlafaxine should not be the sole determinant for multiple
      daily dosing and that antidepressant activity may be more profoundly influenced
      by a drug's pharmacodynamic half-life than by its pharmacokinetic half-life.

PMID- 9632035
TI  - A post hoc comparison of paroxetine and nortriptyline for symptoms of traumatic
      grief.
AB  - BACKGROUND: This report presents the results of an open-trial pilot study of
      paroxetine for symptoms of traumatic grief, compared with the effects of
      nortriptyline in an archival contrast group. METHOD: Data are presented on 15
      subjects (4 men, 11 women), ranging in age from 40 to 79 years (mean age = 57
      years), who experienced the loss of a spouse (N = 8), child (N =5), grandchild (N
      = 1), or parent (N = 1). Subjects were required to have a baseline score on the
      Inventory of Complicated Grief (ICG) of > or = 20. Treatment with paroxetine
      began at a median of 17 months (range, 6-139 months) after the loss. Paroxetine
      treated subjects received a psychotherapy tailored for traumatic grief.
      Depressive symptoms were assessed by using the Hamilton Rating Scale for
      Depression (HAM-D). The ICG and the HAM-D were administered weekly over 4 months
      of paroxetine treatment (median dose = 30 mg/day). The group receiving paroxetine
      were then compared with a group (N = 22) participating in a separate trial of
      nortriptyline (median dose = 77.5 mg/day) for treatment of bereavement-related
      major depressive episodes. RESULTS: Level of traumatic grief symptoms (ICG)
      decreased by 53%, and depression ratings (HAM-D) decreased by 54% in paroxetine
      treated subjects. Nortriptyline showed clinical effects comparable to those of
      paroxetine. CONCLUSION: Paroxetine may be an effective agent in the treatment of
      traumatic grief symptoms. A comparison of the paroxetine-treated group with a
      nortriptyline-treated group suggests that both agents have comparably beneficial
      effects on the symptoms of traumatic grief (as well as those of depression).
      However, the higher rate of diagnostic comorbidity in the paroxetine-treated
      group, together with the greater chronicity of their symptoms and the greater
      safety of paroxetine in overdose, leads us to favor paroxetine over nortriptyline
      for traumatic grief symptoms in general psychiatric practice. Further controlled
      evaluation of paroxetine for traumatic grief is necessary.

PMID- 9632036
TI  - A double-blind, placebo-controlled trial of nefazodone in the treatment of
      patients hospitalized for major depression.
AB  - BACKGROUND: There are few published placebo-controlled clinical trials
      demonstrating the efficacy of the newer antidepressants in markedly or severely
      depressed hospitalized patients. This study demonstrates the efficacy of
      nefazodone compared with placebo in the treatment of patients hospitalized for
      major depression. METHOD: Nefazodone and placebo treatment were compared in a 6
      week trial of 120 patients hospitalized for DSM-III-R diagnosed major depression
      (without psychosis) at 2 study centers. Efficacy was evaluated using standard
      psychiatric rating scales, and patients were monitored for safety. RESULTS:
      Nefazodone treatment resulted in a significant reduction (p < .01) of the 17-item
      Hamilton Rating Scale for Depression (HAM-D-17) total score compared with placebo
      from the end of the first treatment week through the end of the study (-12.2
      nefazodone vs. -7.7 placebo). At the end of the trial, significantly more
      nefazodone-treated patients (50%) than placebo-treated patients (29%) had
      responded, as indicated by their Clinical Global Impressions-Improvement score (p
      = .021) or by a > or = 50% reduction in their HAM-D-17 scores (p = .017).
      Significantly more patients treated with nefazodone (36%) than placebo-treated
      patients (14%) had a HAM-D-17 score < or = 10 at the end of treatment (p = .004).
      Significant treatment differences (p < .01) in favor of nefazodone were also seen
      in the Montgomery-Asberg Depression Rating Scale; the HAM-D retardation, anxiety,
      and sleep disturbance factors; and HAM-D item 1 (depressed mood). Patients with
      dysthymia in addition to major depression also showed significant improvement (p
      < .05) when treated with nefazodone, with significant differences in response
      rates seen as early as week 2 and through the end of the trial. The mean
      nefazodone dose was 491 mg/day at the end of week 2 and 503 mg/day at the end of
      treatment. Nefazodone was well tolerated, and the number of patients
      discontinuing owing to adverse events was small, with no significant safety
      issues noted in either treatment group. Fewer nefazodone-treated than placebo
      treated patients discontinued owing to lack of efficacy. CONCLUSION: Nefazodone
      was superior to placebo in the treatment of marked to severe major depression in
      patients requiring hospitalization. The clinical benefit of nefazodone was
      evident as early as the first week of treatment as judged by several measures of
      efficacy, with significant differences from placebo sustained throughout the
      trial.

PMID- 9632037
TI  - Is risk of neuroleptic malignant syndrome increased in the postpartum period?

PMID- 9632038
TI  - FINISH: remembering the discontinuation syndrome. Flu-like symptoms, Insomnia,
      Nausea, Imbalance, Sensory disturbances, and Hyperarousal (anxiety/agitation)

PMID- 9632039
TI  - Risperidone may worsen fluoxetine-treated OCD.

PMID- 9632040
TI  - Nefazodone and the treatment of panic.

PMID- 9632041
TI  - Gastroesophageal reflux as a possible result of clozapine treatment.

PMID- 9632042
TI  - Atypical antipsychotic agents in the treatment of schizophrenia and other
      psychiatric disorders. Part I: Unique patient populations.

PMID- 9632043
TI  - Hoarding: a symptom, not a syndrome.
AB  - BACKGROUND: Hoarding behavior in humans spans a continuum from normal collecting
      to pathological self-neglect and can be associated with a variety of psychiatric
      disorders. METHOD: The authors summarize research in the past 15 years
      characterizing hoarding behavior in groups of college students, in nonclinical
      populations of self-named "pack rats," in outpatients treated for obsessive
      compulsive disorder (OCD), and in individual pathological hoarders presented in
      psychiatric case reports. Two new case reports of pathological hoarding are
      presented here. RESULTS: The literature suggests, as do the 2 case reports
      presented, that certain factors may be common to all groups of hoarders, as they
      all show poor insight, lack of resistance to the compulsion to hoard, and poor
      treatment motivation. CONCLUSION: Possible biological and psychosocial
      determinants of pathological hoarding include association with schizophrenia,
      OCD, and tic disorders, as well as a possible link through the neurotransmitter
      dopamine. Management issues range from psychopharmacologic treatment with
      antipsychotic medication to behavioral therapy and environmental manipulation.

PMID- 9632044
TI  - Fetal alcohol syndrome: the 'American Paradox'.
AB  - Nearly all cases of fetal alcohol syndrome (FAS) identified in prospective
      epidemiological studies have been conducted in the United States of America. The
      very high incidence rate for FAS in the USA and the relatively low rate in other
      countries does not correspond to measures of alcohol consumption. By analogy with
      the 'French paradox', we have termed the high rate of FAS in the USA coupled with
      its relatively low level of alcohol consumption, the 'American paradox'.

PMID- 9632045
TI  - ESBRA 1997 Award lecture: relationship between excessive alcohol drinking and
      viral infections.
AB  - Several epidemiological studies suggest that chronic alcoholics are at risk of
      viral infections. Clinical and basic research has demonstrated that alcohol not
      only worsens the natural history of chronic viral hepatitis, but also seems to
      interact with the viral replication cycle leading to an unusual serum virological
      profile and/or modification in the serum concentration of viral particles.
      Infections with hepatitis B and C viruses are a major risk for the development of
      hepatocellular carcinoma in excessive drinkers who should be protected against
      these viruses.

PMID- 9632046
TI  - The effect of diazepam on voluntary ethanol intake in a rat model of alcoholism.
AB  - This paper reports the effects of a diazepam treatment on voluntary ethanol
      intake in rats included in an animal model of alcoholism. In a first dose-seeking
      experiment, rats had a choice between 10% (w/v) ethanol and water for 24 h each
      week. Single doses of diazepam between 2 and 20 mg/kg injected i.p. prior to the
      24-h choice caused a dose-dependent decrease in voluntary ethanol intake from 3.2
      +/- 0.4 g/kg/day down to 2.3 +/- 0.3 g/kg/day (P < 0.01) after a dose of 20
      mg/kg. In a second experiment, psychological dependence was induced by a 1-year
      intermittent exposure to ethanol (a choice between 10% ethanol and water for 24 h
      each week, followed by an i.p. injection of 2.0 g/kg of ethanol). After this
      year, the rats were given a continuous choice between ethanol and water. A 3-week
      treatment with diazepam (20 mg/kg/day, i.p.) was started in week 68, during which
      period a choice of 10% (w/v) ethanol was available only on the first and the last
      days of treatment. On the first day of the diazepam treatment, ethanol intake was
      decreased from a pre-experimental value of 2.7 +/- 0.3 g/kg/day to 1.2 +/- 0.1
      g/kg/day (P < 0.001). On the last day of the treatment, voluntary intake was
      higher than before the treatment (3.8 +/- 0.27 g/kg/day, P < 0.01). Ethanol
      intake remained elevated during the week after the end of the diazepam treatment
      (P < 0.05). When single doses of diazepam (20 mg/kg) were re-tested 10 and 19
      weeks after the treatment, there was no decrease in ethanol intake, indicating
      that the initial effect had not been re-established.

PMID- 9632047
TI  - Tryptophan metabolism in male Sardinian alcohol-preferring (sP) and -non
      preferring (sNP) rats.
AB  - Parameters of tryptophan (Trp) and related metabolism were compared in male
      Sardinian alcohol-preferring (sP) and -non-preferring (sNP) rats. Liver Trp
      pyrrolase activity was 38-58% higher in sP than in sNP rats, and this was
      associated with a greater expression of the enzyme mRNA as measured by multiprobe
      oligonucleotide solution hybridization. Moderately (about 10-19%), but
      significantly, lower concentrations of free serum, total serum, and brain Trp
      were also observed in sP compared with sNP rats. Concentrations of whole brain 5
      hydroxytryptamine (5-HT) and its major metabolite 5-hydroxyindol-3-yl-acetic acid
      (5-HIAA) were, however, 14-21% higher in sP rats. Serum corticosterone
      concentration was 18% higher in sP rats. We conclude that alcohol preference in
      Sardinian rats is associated with increased liver Trp pyrrolase activity and mRNA
      expression leading to a decrease in Trp availability to the brain. Although a
      simple serotonin deficiency could not be demonstrated in the whole brain, the
      possibility could not be ruled out that a deficiency may be present in discrete
      areas of the brain of the sP rat.

PMID- 9632048
TI  - Serotonin is reduced in the frontal cortex of Sardinian ethanol-preferring rats.
AB  - Ethanol-naive Sardinian alcohol-preferring (sP) and Sardinian alcohol-non
      preferring (sNP) rats were tested to evaluate the levels of serotonin (5-HT) and
      5-hydroxyindol-3-yl-acetic acid (5-HIAA) in the frontal cortex, hypothalamus, and
      nucleus accumbens, and the levels of dopamine (DA) and 3,4-dihydroxyphenylacetic
      acid (DOPAC) in the hypothalamus and nucleus accumbens. Compared with the sNP
      line, the sP rats had lower 5-HT and 5-HIAA concentrations in the frontal cortex,
      whereas no differences were found in the other brain areas tested, neither for
      neurotransmitters nor their metabolites. As the decreased 5-HT function is a
      feature shared by different alcohol-preferring strains, it could be linked to the
      genetic predisposition to voluntary ethanol consumption.

PMID- 9632049
TI  - Irreversibility of kindled alcohol-withdrawal behaviour in rats.
AB  - In order to investigate whether alcohol-withdrawal kindling is an irreversible
      process, male Wistar rats were exposed to 12 episodes, each consisting of 2 days
      of severe alcohol intoxication and 5 days of alcohol withdrawal. Spontaneous
      withdrawal seizures were found in 15% of the animals during episodes 10-12. After
      an alcohol-free period of 26 days, the animals were subjected to three more
      episodes of alcohol dependence (i.e. episodes 13-15) in which 12% of the animals
      developed spontaneous withdrawal seizures. Based on several statistical tests, we
      concluded that there was no true difference between the seizure activity in
      episodes 10-12 and episodes 13-15, indicating that alcohol-withdrawal kindling is
      a long-lasting and perhaps irreversible process. In a second experiment, an
      alcohol-withdrawal kindled group was first exposed to seven episodes of alcohol
      dependence. A diazepam group went through the same alcohol regimen, but each
      withdrawal reaction was blocked by diazepam treatment. Finally, a single episode
      group was included which was fed isocalorically with the kindled animals. After
      an alcohol-free period of 11 days, all three groups were subjected to 4 days of
      severe alcohol intoxication. During the subsequent withdrawal reaction seizures
      were observed in 22-26% of the animals with no significant differences across the
      groups. These results call for a modification of the kindling hypothesis of
      alcohol withdrawal and suggest that kindling-induced alterations may be
      overlooked if convulsive behaviour is tested during a relatively strong
      withdrawal reaction.

PMID- 9632050
TI  - Electrical amygdala kindling in alcohol-withdrawal kindled rats.
AB  - Repeated alcohol withdrawal has been shown to kindle seizure activity. The
      purpose of the present investigation was to study electrical amygdala kindling in
      rats previously exposed to alcohol-withdrawal kindling. In three independent
      experiments, male Wistar rats were subjected to multiple episodes each consisting
      of 2 days of severe alcohol intoxication and 5 days of alcohol withdrawal. In the
      first experiment, the alcohol-withdrawal kindled animals were divided into two
      groups depending on whether spontaneous alcohol-withdrawal seizures were observed
      in episodes 10-13. In the second and third experiments, the alcohol-withdrawal
      kindled animals were compared to a group in which alcohol-withdrawal kindling was
      prevented by diazepam treatment during the withdrawal reactions in order to
      discriminate between the effect of withdrawal and intoxication. Electrical
      kindling was initiated 28-35 days after the last alcohol dose by exposing the
      animals to daily electrical stimulations of the right amygdala. The results
      showed that amygdala kindling was facilitated in alcohol-withdrawal kindled
      animals which showed spontaneous withdrawal seizure activity, compared with
      animals exposed to multiple episodes of alcohol withdrawal which did not develop
      withdrawal seizures or with animals exposed to a single episode of alcohol
      intoxication. When compared to the control group, the alcohol-withdrawal kindled
      group with seizures also kindled at a faster rate, but the difference did not
      reach statistical significance and therefore the results must be regarded as
      preliminary at present.

PMID- 9632051
TI  - Prevalence of ICD-10 harmful use of alcohol and alcohol dependence among the
      rural population in Udmurtia.
AB  - A sample of 855 rural adult inhabitants in Udmurtia was interviewed by the
      Composite International Diagnostic Interview 1:1 (CIDI) to investigate the
      incidence and prevalence of alcohol-related disorders. Harmful use of alcohol and
      alcohol dependence affected 37.1% of the population according to ICD-10 and DSM
      III-R in a lifetime period. The incidence of alcohol dependence in the previous
      year was 0.8% (1.4% in men, 0.4% in women). Alcohol-related disorders were more
      common in men (72.6%) than in women (10.3%). Correlates of alcohol dependence
      were sex (69.3% in men, 3.7% in women), lower education (40.1%) and being
      divorced in men (77.8%). Alcohol dependence had a high comorbidity with social
      phobia in Udmurt men and with depression in Russian men.

PMID- 9632052
TI  - Treatment, Alcoholics Anonymous and alcohol controls during the decrease in
      alcohol problems in Alberta: 1975-1993.
AB  - In this study, the trends in alcohol consumption, alcohol-related problems,
      alcohol availability and treatment efforts were examined for the province of
      Alberta, for the period 1975-1993. Most of the trends previously observed in
      Ontario were also observed in Alberta. We found: (1) stabilization followed by
      important declines in per capita consumption of alcohol; (2) large decreases in
      most measures of problems such as cirrhosis mortality and traffic fatalities
      related to drinking; (3) increases in treatment and Alcoholics Anonymous
      membership rates; (4) increases in measures of physical availability of alcohol.
      One problem, impaired driving arrest rate, increased substantially during the
      years examined.

PMID- 9632053
TI  - Characteristics of aldehyde dehydrogenases of certain aerobic bacteria
      representing human colonic flora.
AB  - We have proposed the existence of a bacteriocolonic pathway for ethanol oxidation
      resulting in high intracolonic levels of toxic and carcinogenic acetaldehyde.
      This study was aimed at determining the ability of the aldehyde dehydrogenases
      (ALDH) of aerobic bacteria representing human colonic flora to metabolize
      intracolonically derived acetaldehyde. The apparent Michaelis constant (Km)
      values for acetaldehyde were determined in crude extracts of five aerobic
      bacterial strains, alcohol dehydrogenase (ADH) and ALDH activities of these
      bacteria at conditions prevailing in the human large intestine after moderate
      drinking were then compared. The effect of cyanamide, a potent inhibitor of
      mammalian ALDH, on bacterial ALDH activity was also studied. The apparent Km for
      acetaldehyde varied from 6.8 (NADP+-linked ALDH of Escherichia coli IH 13369) to
      205 microM (NAD+-linked ALDH of Pseudomonas aeruginosa IH 35342), and maximal
      velocity varied from 6 nmol/min/mg (NAD+-linked ALDH of Klebsiella pneumoniae IH
      35385) to 39 nmol/min/mg (NAD+-linked ALDH of Pseudomonas aeruginosa IH 35342).
      At pH 7.4, and at ethanol and acetaldehyde concentrations that may be prevalent
      in the human colon after moderate drinking, ADH activity in four out of five
      bacterial strains were 10-50 times higher than their ALDH activity. Cyanamide
      inhibited only NAD+-linked ALDH activity of Pseudomonas aeruginosa IH 35342 at
      concentrations starting from 0.1 nmM. We conclude that ALDHs of the colonic
      aerobic bacteria are able to metabolize endogenic acetaldehyde. However, the
      ability of ALDHs to metabolize intracolonic acetaldehyde levels associated with
      alcohol drinking is rather low. Large differences between ADH and ALDH activities
      of the bacteria found in this study may contribute to the accumulation of
      acetaldehyde in the large intestine after moderate drinking. ALDH activities of
      colonic bacteria were poorly inhibited by cyanamide. This study supports the
      crucial role of intestinal bacteria in the accumulation of intracolonic
      acetaldehyde after drinking alcohol. Individual variations in human colonic flora
      may contribute to the risk of alcohol-related gastrointestinal morbidity.

PMID- 9632054
TI  - Event-related potentials elicited by infrequent non-target stimuli in young
      children of alcoholics: family history and gender differences.
AB  - This article analyses the visual and auditory event-related potentials (ERPs)
      elicited by infrequent non-target stimuli in young children with alcoholic
      fathers. The aim was to study the characteristics of the ERP waves specifically
      evoked by stimuli which capture the attention of the subject in young ones at
      risk for alcoholism, and to assess the effect of sample factors which can
      modulate these characteristics, namely family history of alcoholism and gender.
      There were no differences related to risk for alcoholism on the auditory ERPs.
      However, males and females with a multigenerational family history of alcoholism
      showed significant differences on visual ERP latencies, although different waves
      were affected for each gender. Females showed a larger latency of the visual
      frontal negative wave, Nc, and males showed a larger latency of the visual
      parietocentral P300 wave.

PMID- 9632055
TI  - The detoxification experience of alcoholic in-patients and predictors of outcome.
AB  - This paper reports the detoxification experience and outcome at 6 months and 1
      year following detoxification from alcohol in 160 patients admitted to a south
      east London in-patient detoxification unit. Patients' socio-demographic
      characteristics are also described. The sample was predominantly middle-aged,
      mainly male, and highly dependent on alcohol. Subjects had been drinking heavily
      for many years and suffered physical and social complications in consequence. The
      rate of convulsions was 3.1% and of delirium tremens 1.25%. The details of the
      level of drug usage during detoxification and the assessment of severity of the
      withdrawal syndrome are also reported. The severity of the withdrawal syndrome
      and the incidence of significant complications of withdrawal were higher in those
      with a previous history of four or more episodes of detoxification, a previous
      history of withdrawal fits or evidence of high levels of tolerance and dependence
      assessed either by the Severity of Alcohol Dependence Questionnaire (SADQ) or by
      drinking on a typical heavy drinking day in excess of 24 U of alcohol. It is
      suggested that subjects with one or more of these attributes should be treated on
      an in-patient, rather than an out-patient, basis unless adequate support and
      monitoring systems are in place. Overall, patients made improvements on a wide
      range of social and psychological variables, but the 'abstinent' and 'controlled
      drinking' groups made significantly higher improvements on all variables in both
      follow-up periods. When patients improved their drinking status and reduced the
      levels of drink-related physical and social complications, in both time periods,
      their use of social and health resources decreased significantly. Living
      circumstances at intake were predictive of drinking status at both follow-up
      stages. The amount drunk on a heavy drinking day, at both follow-up stages, was
      predicted by severity of withdrawal, SADQ and living circumstances at intake in
      that order of importance.

PMID- 9632056
TI  - Measurement of carbohydrate-deficient transferrin (CDT) in a general medical
      clinic: is this test useful in assessing alcohol consumption.
AB  - The aim of this study was to measure serum carbohydrate-deficient transferrin
      (CDT) in consecutive patients attending a general medical clinic with a range of
      alcohol intakes to determine its value in assessing such intake. Eighty-one
      consecutive patients (42 male, 39 female) aged 20-85 years (median = 49.5 years)
      attending an out-patient clinic were selected for the study. Each patient
      completed an alcohol diary detailing the units of alcohol consumed in the
      previous week, a CAGE questionnaire and an alcohol history, and underwent
      conventional blood tests including mean corpuscular volume (MCV), liver function
      tests, and gamma-glutamyl transferase (GGT). CDT was estimated using an enzyme
      immunoassay (CDTect, Pharmacia). The group comprised of 17 teetotallers, 28 light
      (<100 g/week), 23 moderate (100-400 g/week), and 13 heavy (>400 g/week) drinkers.
      Median serum CDT for heavy drinkers (25.5 U/l) was significantly higher than for
      the rest (median = 17 U/l, Kruskal-Wallis test, P = 0.01). Serum CDT correlated
      significantly with the CAGE score (Mann-Whitney test, P = 0.01), but poorly with
      alcohol diary records (r = 0.1, P = 0.4). However the correlations between GGT
      and diary records (r = 0.43, P = 0.001) and MCV with diary records (r = 0.5, P <
      0.001) were significant. Sensitivity, specificity, and positive predictive value
      for elevated serum CDT were 69, 81 and 41% respectively in detecting heavy
      drinking. The positive predictive values for the various parameters were 43% for
      elevated serum GGT, 41% for raised erythrocyte MCV, and 75% for a positive score
      on the CAGE questionnaire. When a combination of the markers CDT, GGT, and MCV
      was used, elevation in two of the three markers detected heavy drinking with
      sensitivity of 85%, specificity of 88%, and positive predictive value of 61%. We
      conclude that, in out-patients with a wide range of alcohol intakes conventional
      markers such as serum GGT and erythrocyte MCV were more suitable than serum CDT
      for assessing alcohol intake. Serum CDT when used in combination with serum GGT
      and erythrocyte MCV was useful in detecting heavy drinking. The importance of
      careful history-taking including a standardized questionnaire is emphasized.

PMID- 9632057
TI  - Stress and ethanol metabolism.

PMID- 9632058
TI  - Stress, alcohol metabolism and burn injury.

PMID- 9632059
TI  - High prevalence and impact of rheumatic diseases is not reflected in the medical
      curriculum: the ILAR Undergraduate Medical Education in Rheumatology (UMER) 2000
      project. Together everybody achieves more. International League of Associations
      for Rheumatology.

PMID- 9632060
TI  - Do androgens influence the pathophysiology of rheumatoid arthritis? Facts and
      hypotheses.

PMID- 9632061
TI  - Expression and function of CD40 in rheumatoid arthritis synovium.
AB  - OBJECTIVE: To determine the involvement of CD40 in chronic activation of
      rheumatoid arthritis (RA) synovial monocytes. METHODS: CD40 expression on RA
      synovial monocytes was examined by immunostaining. Involvement of CD40 in tumor
      necrosis factor-alpha (TNF-alpha) secretion from RA synovial fluid mononuclear
      cells (SFMC) was examined by blocking with anti-CD40 antibody. RESULTS: CD40 was
      expressed on RA synovial monocytes. TNF-alpha secretion from RA SFMC was enhanced
      by CD40 ligand stimulation. Spontaneous secretion of TNF-alpha from RA SFMC was
      inhibited by anti-CD40 antibody. CONCLUSION: CD40 was involved in the activation
      of RA synovial monocytes that leads to TNF-alpha production.

PMID- 9632062
TI  - P-selectin as a circulating molecular marker in rheumatoid arthritis with
      thrombocytosis.
AB  - OBJECTIVE: To compare plasma concentrations of soluble P-selectin (sP-selectin)
      in patients with rheumatoid arthritis (RA) and thrombocytosis with those with RA
      with normal platelet counts and healthy controls, and to explore the relationship
      between clinical and serological measures of disease activity. METHODS: Nineteen
      patients with RA with marked thrombocytosis, 20 with normal platelet counts, and
      24 controls were enrolled. Ritchie articular index and morning stiffness were
      recorded as clinical markers of disease activity. Blood samples were collected
      for platelet count, erythrocyte sedimentation rate (ESR), C-reactive protein
      (CRP), and plasma sP-selectin determinations. Correlations between sP-selectin
      and clinical and serological markers of disease activity were noted. RESULTS:
      Patients with RA and thrombocytosis compared to patients with normal platelet
      counts showed evidence of more active disease when ESR, CRP, morning stiffness,
      and Ritchie articular index were considered. The thrombocyte count in patients
      with RA with marked thrombocytosis revealed a positive correlation with CRP and
      Ritchie articular score. Plasma sP-selectin levels were found to be significantly
      higher in patients with RA compared to controls. sP-selectin levels were
      significantly higher in patients with RA with thrombocytosis compared to those
      with normal platelet counts, and positive correlations were observed between
      plasma sP-selectin levels and Ritchie index, morning stiffness, and thrombocyte
      counts in those patients. CONCLUSION: Elevated plasma sP-selectin levels in RA
      could indicate the presence of a continuous underlying inflammatory stimulus. In
      addition, the augmented increase in patients with RA and thrombocytosis and its
      correlation with clinical activity may imply the cytokine-adhesion molecule
      interaction mediates the chronic inflammation of RA.

PMID- 9632063
TI  - Salivary testosterone in postmenopausal women with rheumatoid arthritis.
AB  - OBJECTIVE: To study changes in testosterone concentrations in saliva and total
      testosterone, free testosterone, and sex hormone binding globulin (SHBG)
      concentrations in serum in 2 groups of postmenopausal women with rheumatoid
      arthritis (RA), one group with glucocorticoid treatment and the other without it.
      METHODS: The above mentioned hormonal levels were measured in 20 postmenopausal
      women with RA undergoing glucocorticoid treatment, in 24 postmenopausal women
      with RA without treatment, and in 36 postmenopausal women without RA. RESULTS: We
      observed significantly lower levels of total testosterone in serum, SHBG in
      serum, testosterone in saliva, and the free testosterone index in the group of
      patients with RA undergoing glucocorticoid treatment compared to the group
      without treatment. We did not observe changes in free testosterone concentrations
      in serum of the groups studied, which is believed due to its lower specificity.
      CONCLUSION: Testosterone in saliva is a useful indicator for monitoring
      androgenic status in women with RA.

PMID- 9632064
TI  - Comparison of the original and the modified Larsen methods and the Sharp method
      in scoring radiographic progression in early rheumatoid arthritis.
AB  - OBJECTIVE: To compare the original Larsen method and the proposed modification of
      the Larsen method with omission of scoring soft tissue swelling and periarticular
      osteoporosis, and the Sharp method in measurement of radiographic progression in
      early rheumatoid arthritis (RA). METHODS: Radiographs of hands and feet were
      assessed by the 3 scoring methods at Months 0 and 12 in 83 patients with recent
      onset RA. Sensitivity to change was determined using standardized response mean
      (SRM). RESULTS: Highly significant radiographic progression was observed by all 3
      methods. The modified Larsen method showed the largest SRM (0.88), but the
      differences were slight between the 3 scoring methods (SRM 0.80 for the original
      Larsen method, SRM 0.72 for the Sharp method). High interobserver reproducibility
      was observed for all methods tested. CONCLUSION: In early RA the sensitivity to
      change of all 3 scoring methods was high, but in this patient population the
      newly modified Larsen method was the most responsive method.

PMID- 9632065
TI  - Enhanced expression of immunoglobulin kappa light chains with unusually long CDR3
      regions in patients with rheumatoid arthritis.
AB  - OBJECTIVE: Our previous sequence analysis of immunoglobulin kappa light chains
      revealed that some patients with rheumatoid arthritis (RA) expressed repertoires
      enriched for transcripts containing unusually long CDR3 lengths of 11 amino acid
      codons. This was due, in part, to N region addition at the Vkappa-Jkappa joins.
      In this study, we analyzed a larger number of individuals to determine how often
      enrichment of kappa light chain repertoires for 11 amino acid CDR3 occurs in
      synovial lymphocytes and peripheral blood lymphocytes (PBL) of individuals with
      RA. METHODS: To measure length variability of kappa chain CDR3 regions, we
      performed a 2 stage polymerase chain reaction amplification and polyacrylamide
      gel electrophoresis. We sampled PBL and synovial lymphocytes of 9 patients with
      longstanding RA, and used PBL of 9 age and sex matched healthy individuals as
      controls. RESULTS: In PBL of healthy individuals, there was low level but
      consistent expression of kappa chains containing CDR3 with 11 amino acids. In
      patients, there was enhanced expression of kappa chains containing CDR3 with 11
      amino acids compared to healthy individuals. This enhanced expression of kappa
      chains containing CDR3 of 11 amino acids was more pronounced in synovial
      lymphocytes compared to PBL of the same patients. CONCLUSION: These findings
      suggest that there is antigenic selection of B cells bearing antibodies with
      unusually long kappa light chain CDR3 in RA.

PMID- 9632066
TI  - Longterm mortality outcome in patients with rheumatoid arthritis: early
      presenters continue to do well.
AB  - OBJECTIVE: Patients with rheumatoid arthritis (RA) have reduced life expectancy;
      however, there are few data on the changing pattern of causes of death with
      longterm followup, or on the longterm effect of early presentation. The
      objectives of this study were (1) to examine the effect of early presentation on
      subsequent mortality; (2) to compare the causes of death early and late in the
      followup period; and (3) to compare survival of the cohort with that of the
      general population (adjusted for age and sex) over a followup period of up to 27
      years. METHODS: A cohort of 448 patients with RA (inpatients and outpatients),
      assembled 1968-74, were followed to December 31, 1990. Death certificates were
      obtained for all who had died and coded using the International Classification of
      Diseases. Kaplan-Meier survival curves were constructed. RESULTS: By the end of
      the study, 266 patients (59%) had died. The standardized mortality ratio (SMR)
      was 2.7 (95% CI 2.4-3.1). Patients who presented early continued to do well. Most
      excess deaths were due to cardiovascular disease. SMR due to infection, renal
      failure, and non-Hodgkin's lymphoma rose with disease duration. CONCLUSION:
      Patients with RA should be referred early, and those with chronic disease should
      be closely monitored for evidence of infection and renal impairment.

PMID- 9632067
TI  - The incidence and severity of rheumatoid arthritis, results from a county
      register in Oslo, Norway.
AB  - OBJECTIVE: To examine the incidence of rheumatoid arthritis (RA) in the community
      of Oslo, Norway; and to link the incidence to measures of disease severity.
      METHODS: A register for RA in the county of Oslo was validated to be 85% complete
      for patients between 20 and 79 years of age. The incidence of RA was calculated
      from this register for patients with disease onset 1988-1993 (n=550). Data on
      health related quality of life [Modified Health Assessment Questionnaire (MHAQ),
      Arthritis Impact Measurement Scale 2 (AIMS2), pain, fatigue] were obtained from a
      postal survey (response rate 73%). RESULTS: The overall annual incidence of RA
      over a 6 year period was 25.7/100,000 (females 36.7, males 13.8). The incidence
      increased with age, from 7.8 in the age group 20-29 to 61.0 between 70 and 79
      years. After 5 year followup a clinically important effect on physical function
      (MHAQ > 1.5) was seen in 38% of the patients, on social functioning (AIMS2 social
      > 4) in 50%, on mental distress (AIMS2 affect > 4) in 27%, on pain (VAS > 40 mm)
      in 35%, and on fatigue (VAS > 40 mm) in 41%. CONCLUSION: The incidence of RA was
      25.7/100,000 in the population of Oslo. After 5 years, 40-50% had clinically
      important changes in health status. The annual disease incidence with clinically
      important effect on physical function after 5 years was 10/100,000 individuals at
      risk.

PMID- 9632068
TI  - Expression of costimulatory molecule CD80 on peripheral blood T cells in patients
      with systemic lupus erythematosus.
AB  - OBJECTIVE: To investigate the expression of costimulatory molecule CD80 on T
      cells of peripheral blood mononuclear cells (PBMC) in patients with systemic
      lupus erythematosus (SLE). METHODS: Monoclonal antibodies against CD80 were used
      for flow cytometry and expression of CD80 on PBMC was studied in 26 patients with
      SLE, 18 patients with rheumatoid arthritis (RA), 8 patients with mixed connective
      tissue disease (MCTD), and 22 healthy controls. RESULTS: CD80 was detected on
      CD3+ and CD19+ cells in patients with SLE and it was significantly higher than
      that of controls. In patients with SLE CD80 was expressed on CD4+ T cells (8.05+/
      5.45%), significantly higher than in RA and controls, but was not highly
      expressed on CD8+ T cells (1.67+/-2.87%). CD80+CD4+ T cell phenotype analysis
      revealed CD45RA-, CD45RO+, and CD25+, or HLA-DR+ activated T cells. The
      percentage of CD80+ cells in CD4+ cells increased in the active stage of SLE, and
      was significantly correlated with the SLE disease activity index. CONCLUSION:
      CD80 can be expressed on activated CD4+ T cells in PBMC of patients with SLE in
      vivo and the appearance of these cells is associated with the disease activity in
      SLE.

PMID- 9632069
TI  - Autonomic dysfunction in patients with systemic lupus erythematosus.
AB  - OBJECTIVE: To assess the prevalence and severity of autonomic dysfunction (AD) in
      patients with systemic lupus erythematosus (SLE). METHODS: Fifty-nine consecutive
      patients with SLE and 97 healthy controls were assessed for AD using 4
      noninvasive tests: heart rate responses to the Valsalva maneuver (Val), maximum
      minimum heart rate (MM) response to deep breathing, heart response to standing up
      (30:15 ratio), and changes in blood pressure to sustained handgrip (Hand). AD was
      categorized as incipient, definite, severe, or atypical according to criteria
      proposed by Ewing. Disease characteristics, comorbid conditions, disease activity
      index [Mexican Systemic Lupus Erythematosus Disease Activity Index (Mex-SLEDAI)],
      cardiac complaints, and drug history were also documented. Laboratory analysis
      included rheumatoid factor, antinuclear antibodies, anti-dsDNA antibodies, and
      anticardiolipin antibodies (aCL). RESULTS: Forty-eight percent of the patients
      with SLE had one or more abnormal tests compared with 33% of the controls
      (p=0.05); differences were greater when the severity of the neuropathy was
      considered: 12 (21%) patients with SLE had definite or severe AD using Ewing's
      criteria, compared with only 2 (2%) controls (p < 0.001). No statistical
      associations were observed between AD and age, disease duration, hypertension,
      Mex-SLEDAI, anti-dsDNA, aCL antibodies, or other drugs. CONCLUSION: The
      prevalence of AD in SLE using noninvasive tests is high. One-fifth of our
      patients had definite or severe AD. No significant associations were observed
      between AD and clinical or serological variables of disease activity. Prospective
      studies are needed to determine the potential effect of AD in the morbidity of
      patients with SLE.

PMID- 9632070
TI  - Evaluation of the hypothalamic-pituitary-gonadal axis in males with systemic
      lupus erythematosus.
AB  - OBJECTIVE: To evaluate the hypothalamic-pituitary-gonadal axis in male patients
      with systemic lupus erythematosus (SLE). METHODS: We studied 7 male patients with
      SLE and compared them with 10 age matched healthy controls. Clinical data,
      laboratory tests, drugs used, and disease activity for SLE (SLE Disease Activity
      Index) were determined. The basal serum levels of cortisol, total testosterone
      (T), free testosterone (FT), androstenedione, dehydroepiandrosterone sulfate
      (DHEAS), estradiol (E2), prolactin (PRL), luteinizing hormone (LH), and follicle
      stimulating hormone (FSH) were measured in all individuals. In addition, response
      of LH and FSH to stimulation with luteinizing hormone releasing hormone (LHRH,
      100 microg, intravenously) and response of T and FT to stimulation with human
      chorionic gonadotropins (HCG, 1500 u intramuscular for 3 days) were examined.
      RESULTS: Patients with SLE had lower basal levels of T and FT than controls but
      this difference was not significant. DHEAS and A levels were significantly lower
      in patients than in controls. The low response of FT after stimulation with HCG
      indicated diminished testis function (mainly Leidyg cells). In contrast to other
      studies, the E2 level was significantly lower in patients than in controls. The
      groups did not differ in LH levels at baseline or after stimulation with LHRH.
      However, basal levels of FSH were significantly higher in patients. CONCLUSION:
      These results suggest that the hypothalamic-pituitary-axis function was normal in
      patients with SLE. The testis had diminished function, shown by reduced response
      of FT to stimulation with HCG, but possible inhibitory effects of glucocorticoid
      therapy must be considered.

PMID- 9632071
TI  - Autoantibodies to human prothrombin and clinical manifestations in 207 patients
      with systemic lupus erythematosus.
AB  - OBJECTIVE: Prothrombin (factor II) is one of the phospholipid binding proteins
      with a procoagulant property. Some publications have shown the presence of
      autoantibodies against prothrombin (aPT) in patients with antiphospholipid
      antibodies (aPL). We assessed the clinical significance of aPT in thrombotic
      events in patients with systemic lupus erythematosus (SLE). METHODS: IgG and IgM
      aPT were tested by ELISA in 207 patients with SLE. RESULTS: Fifty-eight patients
      (28%) had positive aPT (> mean + 3 SD of 100 controls). Twenty-eight (14%) had
      IgG alone, 21 (10%) IgM alone, and 9 (4%) had both IgG and IgM. Patients with aPT
      had a history of thrombosis more frequently than those without aPT [31/58 (53%)
      vs 47/149 (32%), chi-squared=7.6, p=0.006]. No correlation was found between the
      presence of aPT and clinical features of SLE. CONCLUSION: aPT are frequently
      found in patients with SLE, and are a potential marker for thrombosis.

PMID- 9632072
TI  - Association of HLA class I and class II alleles with myositis in Japanese
      patients.
AB  - OBJECTIVE: To investigate the correlation of HLA class I and class II antigens
      and alleles with various forms of myositis in Japanese patients. METHODS: Eighty
      four Japanese patients with myositis [22 with polymyositis (PM), 46 with
      dermatomyositis (DM), 16 with myositis overlapping with other collagen vascular
      diseases] were typed serologically for HLA-A, B, C antigens. HLA-DRB1, DQA1, and
      DQB1 alleles were determined by polymerase chain reaction dependent DNA typing
      methods. Fifty-eight Japanese controls were typed serologically while HLA-DRB1,
      DQA1, and DQB1 allele typing was carried out in 175, 95, and 104 controls,
      respectively. RESULTS: HLA-B7 was higher in patients than controls [20.2 vs 6.9%
      in controls: p=0.02, odds ratio (OR)=3.4]. The increase of HLA-B7 was largely
      dependent on the increase in overlap patients (37.5%; p=0.005, OR=8.1). HLA-A24
      and B52 were significantly decreased in PM as compared to DM, while CW3 was
      significantly increased in PM versus DM. DRB1*08 alleles were significantly
      increased in patients (36.9 vs 20.5% in controls; p=0.004, OR=2.3), especially in
      PM and DM. DQA1*0501 and DQB1*0301 were significantly decreased in patients [4.8
      vs 13.7% in controls; p=0.04, OR=0.32, and 8.3 vs 20.2% in controls; p=0.02,
      OR=0.36, respectively]. CONCLUSION: HLA-class I and class II alleles associated
      with Japanese patients with myositis may be different from those associated with
      Caucasian patients.

PMID- 9632073
TI  - Ribavirin in hepatitis C related cryoglobulinemia.
AB  - OBJECTIVE: An open, uncontrolled trial of ribavirin, an oral guanosine nucleoside
      analog for treatment of hepatitis C, in patients with hepatitis C virus (HCV)
      associated cryoglobulinemia intolerant to interferon. METHODS: Five patients with
      cryoglobulinemia related to HCV infection unresponsive to interferon therapy
      received oral ribavirin (100 to 1200 mg daily) for 10 to 36 months. RESULTS:
      Patients treated with ribavirin had prompt decrease in serum aminotransferase
      levels and marked improvement of manifestations of cryoglobulinemia within a few
      weeks. Ribavirin did not eradicate HCV RNA from the sera, but a decrease in viral
      load was observed in 3 patients, from 232 to 86 x 10(5) copies HCV/ml. Relapse
      occurred within 3 months once therapy was discontinued. The drug was well
      tolerated, but mild dose related hemolysis was common. CONCLUSION: Ribavirin
      monotherapy may be effective in patients with symptomatic cryoglobulinemia
      related to HCV infection, but this effect is not sustained when ribavirin therapy
      is discontinued.

PMID- 9632074
TI  - Direct synovial gene transfer with retroviral vectors in rat adjuvant arthritis.
AB  - OBJECTIVE: To evaluate the feasibility of direct in vivo gene transfer in an
      animal model of arthritis using a retroviral vector. METHODS: The timing and dose
      of retroviral vector was examined using very high titer retroviral vector (> or =
      10(9) CFU) in rat adjuvant arthritis. Retroviral vector expressing beta
      galactosidase (beta-gal) or vehicle alone was injected into the right ankle of
      rats with adjuvant arthritis. Ankles were injected either on Day 7 (pre
      arthritis), Day 10 (early arthritis), Day 15 (accelerating arthritis), or Day 28
      (chronic arthritis) after adjuvant immunization. Joints were harvested 3 days
      later and extracts were assayed for beta-gal activity. RESULTS: Synovial beta-gal
      expression was minimal in the Day 7 group and elevated in the Day 10, Day 15, and
      Day 28 groups. Gene transfer with retroviral vector did not exacerbate the local
      inflammatory response. Minimal or no beta-gal expression was observed in the
      contralateral uninjected paw or in the spleen, lung, liver, and kidneys. Frozen
      sections of retroviral vector injected joints were stained with X-gal and
      revealed transduced cells in the lining and superficial sublining layers. To
      determine the longevity of gene expression, ankle joints were injected with
      vector on Day 15 post-adjuvant, harvested, and assayed for beta-gal activity for
      up to 49 days after injection. Expression of the enzyme peaked from Day 3 to 7
      and was still readily detected up to 49 days after retrovirus infection.
      CONCLUSION: This is the first report of successful direct in vivo gene transfer
      in the rat adjuvant arthritis model using a retroviral vector. Appropriate timing
      of administration and very high titer retroviral vector preparations are key
      determinants of adequate gene transduction.

PMID- 9632075
TI  - Reactive arthritis associated with group C and group G beta-hemolytic
      streptococci.
AB  - OBJECTIVE: Group A beta-hemolytic streptococci (GAS) are known to be capable of
      evoking sterile arthritis. Reactive arthritis (ReA) has been reported
      sporadically following primary infection with group C and group G beta-hemolytic
      streptococci (GCS, GGS). We prospectively studied 4 cases of ReA secondary to
      throat infection with GCS and GGS. METHODS: Four patients with arthritis
      secondary to throat infection were seen. Three patients were Dutch, one was
      Indonesian; female/male ratio was 1/3; mean age was 30 years (range 18-46).
      Diagnostic evaluation included culture of throat swab and serological screening.
      RESULTS: All patients presented with a nonmigratory asymmetrical arthritis:
      monoarthritis in one patient, oligoarthritis in 3. Culture of throat swab was
      positive in all. Antistreptolysin-O (ASO) titer rose significantly in 2 patients,
      and anti-DNase-B rose in 2 patients. ASO was maximal (mean 1000 U/ml; range 890
      1110) and anti-DNase-B was 395 U/ml (range 290-500). Treatment consisted of
      feneticillin for 5 days; nonsteroidal antiinflammatory drugs were prescribed on
      demand. All patients recovered fully in 3 to 12 weeks. CONCLUSION: These cases
      provide evidence of a benign non-group A streptococcal ReA, i.e., secondary to
      GCS or GGS. The presence of the organism in the throat along with the elevation
      of antibody to streptococcal products is important for the diagnosis of GCS/GGS
      associated ReA. A positive throat culture is needed for differentiation from GAS
      associated poststreptococcal ReA, because prophylactic measures are effective
      only in GAS associated sequelae, but not in GCS/GGS associated ReA.

PMID- 9632076
TI  - Chronic arthritis in patients with aspartylglucosaminuria.
AB  - OBJECTIVE: To study the frequency and clinical features of chronic inflammatory
      arthritis in aspartylglucosaminuria (AGU), a rare disorder of glycoprotein
      degradation inherited as an autosomal recessive trait and significantly more
      frequent in Finland than in other parts of the world. METHODS: Of the 164
      patients with AGU identified in Finland, 121 were examined by one of the authors,
      and 43 by their own physicians. For this study, we clinically reexamined all
      patients with AGU who had arthritis, and relevant laboratory and radiographic
      studies were performed. RESULTS: Nine of 164 patients (5.5%) were found to have
      chronic inflammatory arthritis. In 5 patients, the symptoms had started in
      childhood. Five were seropositive for rheumatoid factor. Symmetric polyarthritis
      of both small and large joints was seen in 5 patients and erosions in 5.
      Seropositive rheumatoid arthritis was found in 3 first-degree relatives as well.
      CONCLUSION: Chronic inflammatory arthritis is a feature of AGU and is
      characterized by onset in childhood, seropositivity for rheumatoid factor, and a
      deforming course.

PMID- 9632077
TI  - Phagocytic synovial lining cells regulate acute and chronic joint inflammation
      after antigenic exacerbation of smouldering experimental murine arthritis.
AB  - OBJECTIVE: To investigate the in vivo role of phagocytic synovial lining cells in
      inflammation after exacerbation of smouldering murine antigen induced arthritis.
      METHODS: Phagocytic synovial lining cells were selectively depleted, by
      intraarticular injection of clodronate laden liposomes, 2 weeks after induction
      of modified bovine serum albumin induced arthritis. Exacerbation of arthritis was
      induced at Week 3, intravenously or locally into the knee joint. Arthritis was
      evaluated by 99mTc uptake measurements or in hematoxylin and eosin stained
      sections. Retention of radiolabeled antigen was evaluated by external measurement
      of radioactivity or autoradiography. Chemotactic factor production and
      interleukin 1 (IL-1) protein level were detected in washout samples of arthritic
      joints by transwell chemotactic assay and NOB.EL-4 bioassay or
      immunolocalization, respectively. RESULTS: One day after induction of flare,
      swelling measured by 99mTc uptake was similar in control and lining depleted knee
      joints. Histological examination of control reactivated knee joints revealed
      infiltrate in both superficial and deep synovial layers, while florid exudate
      occurred in the joint cavity. In lining depleted reactivated knee joints
      infiltrate was significantly decreased, found mainly in the deep synovial layer
      around the blood vessels, whereas exudate was significantly lower. No difference
      was found in the topography of the synovial infiltrate for antigen given
      intraarticularly versus intravenously. Antigen removal was slowed in lining
      depleted joints and autoradiographs showed antigen persistence mainly in the
      joint cavity and the synovial layer. Reduced influx of inflammatory cells was
      correlated to decreased production of chemotactic factors. Level of IL-1 was
      lower in washouts and was mainly detected in macrophages in the deep layer, as
      shown by immunolocalization. In controls, more IL-1 was detected in the lining
      and subsynovial layer. At Day 7 after exacerbation no synovitis was found in the
      synovial lining cell depleted arthritic joint, whereas florid synovitis persisted
      in the arthritic control joint. CONCLUSION: Phagocytic synovial lining cells are
      involved in acute and chronic inflammation after exacerbation of hyperreactive
      joints with antigen given either directly into the knee joint or intravenously.

PMID- 9632078
TI  - Regulation of cyclooxygenase-2 expression in bovine chondrocytes in culture by
      interleukin 1alpha, tumor necrosis factor-alpha, glucocorticoids, and 17beta
      estradiol.
AB  - OBJECTIVE: To determine the effects of interleukin 1alpha (IL-1alpha), tumor
      necrosis factor-alpha (TNF-alpha), dexamethasone, and 17beta-estradiol on the
      expression of cyclooxygenase-1 (COX-1) and COX-2 in bovine chondrocytes. METHODS:
      Northern blot analysis was used to quantify COX-1 and COX-2 mRNA expression in
      primary cultures of bovine chondrocytes and prostaglandin production to evaluate
      COX activity. RESULTS: IL-1alpha and TNF-alpha increased the expression of COX-2.
      This effect was independent of de novo protein synthesis and dependent on
      increased mRNA stability in the case of IL-1alpha. Dexamethasone inhibited the
      effects of both cytokines. 17beta-estradiol inhibited COX-2 mRNA expression in
      basal conditions, but had no effect on COX-2 expression induced by cytokines. The
      specific COX-2 inhibitor compound NS 398 prevented the increase in prostaglandin
      E2 (PGE2) production induced by the cytokines. COX-1 levels remained stable with
      all treatments. CONCLUSION: Increase in mRNA stability is a mechanism implicated
      in the induction of COX-2 by some cytokines. The effects of IL-1alpha and TNF
      alpha on PGE2 production are mainly due to an increase in COX-2 activity as shown
      by the effect of compound NS 398. 17beta-estradiol inhibits COX-2 mRNA expression
      in basal conditions, suggesting that estrogens could be implicated in the control
      of cartilage metabolism.

PMID- 9632079
TI  - Osteoclast-like cells in murine collagen induced arthritis.
AB  - OBJECTIVE: To investigate the participation of osteoclast-like bone resorbing
      cells in the joint destruction of murine collagen induced arthritis (CIA).
      METHODS: After induction of CIA in DBA/1J mice, a histological time course study
      was conducted on paw sections stained for tartrate resistant acid phosphatase
      (TRAP), a marker of osteoclasts. Cells from arthritic paws were cultured in vitro
      with or without indomethacin (IM) or anti-interleukin 6 neutralizing antibody
      (anti-IL-6), and stained for TRAP. Levels of prostaglandin E2 (PGE2), IL-1beta,
      IL-6, and tumor necrosis factor-alpha in the culture supernatants were determined
      by ELISA. The bone resorbing ability of these cells was examined on dentine
      slices. In control experiments, cells of normal paws or of arthritic tibiae were
      cultured in the same manner. RESULTS: TRAP positive osteoclast-like cells were
      detected late in the development of bone lesions at every eroded front in the
      pannus-bone and the pannus-subchondral bone junctions of arthritic joints. In
      vitro, cells of arthritic paws formed bone resorbing osteoclast-like cells
      spontaneously. However, the control culture failed to form these cells. PGE2 and
      IL-6 were detected at higher levels in arthritic culture than in control culture.
      Although both indomethacin and anti-IL-6 reduced osteoclast-like cell formation
      and indomethacin inhibited PGE2 synthesis, indomethacin failed to reduce IL-6.
      CONCLUSION: These findings suggest the direct participation of osteoclast-like
      cells in the joint destruction of CIA, the locally enhanced activity of
      osteoclast-like cell differentiation in arthritic paws, and the participation of
      prostaglandins and prostaglandin-independent IL-6 in this differentiation.

PMID- 9632080
TI  - Extracorporeal shock wave treatment for chronic calcific tendinitis of the
      shoulder.
AB  - OBJECTIVE: To study the clinical and radiological response of chronic calcific
      tendinitis of the shoulder to extracorporeal shock wave treatment (ESWT).
      METHODS: The study included 3 female patients, 42, 48, and 50 years of age, all
      with calcified tendinitis of the rotator cuff. All had severe shoulder pain and
      limitation of motion. ESWT was done in one session with an extracorporeal shock
      wave lithotripter. RESULTS: After 24 hours, a fragmentation of calcification was
      achieved, and the patients had no pain and had entirely regained their joint
      movement. After 2 years of followup they were clinically and radiologically
      asymptomatic, and there were no adverse effects or other complications.
      CONCLUSION: With its good tolerance, safety, and clinical and radiologic
      response, ESWT should be considered as an alternative therapy in the treatment of
      chronic calcific tendinitis of the shoulder refractory to other therapies.

PMID- 9632081
TI  - Amyloid and non-amyloid carpal tunnel syndrome in patients receiving chronic
      renal dialysis.
AB  - OBJECTIVE: To determine the prevalence of amyloid deposits among patients with
      carpal tunnel syndrome (CTS) receiving dialysis, and to investigate the factors
      associated with amyloid and non-amyloid CTS. METHODS: Subjects for this
      prospective study were dialysis patients who underwent surgery for CTS in the
      same surgical unit between 1989 and 1997. CTS was diagnosed from clinical and
      electromyographic (EMG) findings. Systematic standard radiographs and laboratory
      data were also obtained. Surgical investigations included systematic macroscopic
      examination and biopsy of the epineurium, flexor retinaculum, synovium, and
      flexor tendon sheaths. Samples were stained for amyloid and examined by plain and
      polarized light microscopy, immunohistochemistry, and electron microscopy.
      RESULTS: Forty-one samples from 30 patients (11 bilateral cases) were examined.
      Amyloid deposits were found in 26 samples from 18 patients (7 M, 11 F). Fifteen
      samples from 12 patients (3 M, 9 F) showed no amyloid deposits. Amyloid CTS was
      statistically significantly associated with arthralgia and longterm dialysis
      [mean 13.3 (range 5.5-23) vs 7.5 yrs (range 3 mo-14 yrs)] in non-amyloid CTS.
      Flexor tenosynovitis and carpal bone erosion occurred more frequently in amyloid
      CTS. There were no statistically significant differences between the 2 groups in
      clinical, laboratory or EMG findings, type of dialysis membrane, or frequency of
      ipsilateral fistula. Only amyloid CTS was recurrent. CONCLUSION: Amyloid deposits
      were confirmed microscopically in 63.4% of patients. The relatively large number
      of cases of non-amyloid CTS without signs of dialysis associated arthropathy
      suggests that CTS is not a satisfactory criterion for diagnosis of dialysis
      arthropathy or beta2-microglobulin amyloidosis unless the presence of amyloid has
      been confirmed or duration of dialysis treatment has been at least 15 years.

PMID- 9632082
TI  - Quality of life in osteoporosis: reliability, consistency, and validity of the
      Osteoporosis Assessment Questionnaire.
AB  - OBJECTIVE: To determine the reliability, consistency, and clinical utility of the
      Osteoporosis Assessment Questionnaire (OPAQ), an AIMS2 based self-assessment
      questionnaire. METHODS: Reliability of individual questions, scales, and domains
      were evaluated in 40 subjects by test-retest and intraclass correlation
      coefficients and internal consistency by Cronbach's alpha. Construct validity was
      evaluated by disease state. The relationships between domains and scales were
      modeled by confirmatory factor analysis. RESULTS: Mean kappa (79 questions) and
      intraclass correlation (18 health scales) coefficients were 0.58+/-0.16 (mean+/
      SD) and 0.82+/-0.07, respectively. Internal consistency was greater than 0.8 in
      all but 3 scales. Construct validity was confirmed. Patients with hip fracture
      recorded lower OPAQ scores than patients with vertebral fracture. Correlation and
      confirmatory factor analyses grouped the 18 health scales into 7 domains.
      CONCLUSION: These findings suggest that OPAQ is a reliable, consistent, and valid
      instrument capable of distinguishing hierarchy of functional loss in disease
      states in osteoporosis.

PMID- 9632083
TI  - The effects of delta wave sleep interruption on pain thresholds and fibromyalgia
      like symptoms in healthy subjects; correlations with insulin-like growth factor
      I.
AB  - OBJECTIVE: To assess the effects of delta wave sleep interruption (DWSI) on pain
      thresholds and fibromyalgia-like symptoms. To examine the potential correlations
      between DWSI and serum insulin-like growth factor 1 (IGF-1). METHODS: Thirteen
      healthy volunteers were subjected to 3 consecutive nights of DWSI (Group 1). Pain
      thresholds were measured by dolorimetry and symptoms by visual analog scale. Six
      subjects not undergoing DWSI served as dolorimetry and symptom controls (Group
      2). Serum IGF-1 was measured by competitive binding radioimmunoassay before and
      after DWSI. RESULTS: No significant differences in pain thresholds as a function
      of condition (baseline, DWSI, recovery) or overnight change were detected between
      or within groups (p>0.05). Morning mean dolorimeter scores were lower than
      evening scores in both groups during all 3 conditions, and were lower in Group 1
      than in Group 2 during DWSI. Group 1 subjects had higher composite symptom scores
      during DWSI (p< or =0.005), attributed largely to increases in fatigue. Serum
      levels of IGF-1 from Group 1 subjects showed no significant change after DWSI
      (p>0.05). CONCLUSION: In our study subjects, 3 nights of DWSI caused no
      significant lowering of pain thresholds compared with a control group. Subjects
      appeared to have lower pain thresholds in the mornings, and DWSI appeared to
      augment this effect. Symptoms were more apparent during DWSI, but were primarily
      related to fatigue. IGF-1 was not altered by 3 nights of DWSI. The low levels of
      IGF-1 seen in patients with fibromyalgia syndrome may result from chronic rather
      than acute DWSI, or may be dependent on factors other than disturbances of delta
      wave sleep.

PMID- 9632084
TI  - The first certifying examination in pediatric rheumatology.
AB  - OBJECTIVE: On May 12, 1992, the first certifying examination in pediatric
      rheumatology was administered by the American Board of Pediatrics to 94
      candidates. We describe the certifying process and the characteristics of the
      examinees. METHODS: The Sub-board of Pediatric Rheumatology developed an
      examination consisting of 235 multiple choice items covering a broad range of
      topics pertinent to the subspecialty. Applicants with a current certificate in
      general pediatrics and a current medical license were admitted through one of 3
      pathways requiring 2 years of fellowship training or equivalent practice
      experience. RESULTS: Sixty-three percent of the candidates had completed at least
      2 years of fellowship training. The total group average score was 76% correct.
      Eighty-five percent of the examinees passed the examination. CONCLUSION: The 80
      candidates who were certified received time limited certificates that may be
      renewed by a recertification process to begin in 1999. A second certifying
      examination was offered in 1994 and a third in 1996. Requirements for future
      certifying examinations will include 3 years of full time fellowship training and
      verification of meaningful accomplishment in research.

PMID- 9632085
TI  - Sleep fragmentation in children with juvenile rheumatoid arthritis.
AB  - OBJECTIVE: To characterize sleep patterns of patients with juvenile rheumatoid
      arthritis (JRA). METHODS: Sixteen patients with JRA aged 12+/-4 years and 9
      controls aged 11+/-3 years underwent a comprehensive evaluation by self-report
      questionnaire and formal all night polysomnographic recordings. Multiple sleep
      latency test was performed in 7 patients. RESULTS: Patients had 90% more arousals
      and awakenings (p<0.01) and the median length of occurrences of uninterrupted
      sleep in stages 2 and 3 and rapid eye movement (REM) sleep was 60% shorter than
      in controls (p<0.01). The overall amount of sleep stage shift from deeper to
      lighter sleep was 23.5+/-10.8 events in patients compared to 14.9+/-4.0 in
      controls (p<0.05). In 15 of 16 patients 15% of non-REM sleep consisted of alpha
      delta (alpha-rating) sleep, compared with less than 1% in controls (p<0.001).
      Multiple sleep latency test for patients was 10.3+/-2.6 min. There were no
      differences between JRA and controls in self-reported questions. However,
      patients reported longer afternoon naps, 1.8+/-1.3 h compared to 0.3+/-0.8 h in
      controls (p<0.05). CONCLUSION: Objective polysomnographic evidence of abnormal
      sleep has been confirmed in patients with JRA. Sleep disturbance was associated
      with daytime sleepiness as evidenced by abnormal multiple sleep latency test and
      longer afternoon naptime.

PMID- 9632086
TI  - Juvenile dermatomyositis at diagnosis: clinical characteristics of 79 children.
AB  - OBJECTIVE: To evaluate demographic and clinical characteristics, duration of time
      between disease onset (date of first rash and/or weakness), and
      diagnosis/therapy, as well as socioeconomic status, of children with newly
      diagnosed juvenile dermatomyositis (JDM). METHODS: Structured telephone interview
      of families of a cohort of 79 children with JDM: interval between onset of
      symptoms to diagnosis, median of 3 months (range 0.5-20.0). RESULTS: At
      diagnosis, all the children had rash (100%) and proximal muscle weakness (100%);
      58 (73%) had muscle pain; 51 (65%) fever; 35 (44%) dysphagia; 34 (43%)
      hoarseness; 29 (37%) abdominal pain; 28 (35%) arthritis; 18 (23%) calcinosis, and
      10 (13%) melena. Muscle derived enzymes were normal in 10% of the children. Of
      the 43 children who had an electromyogram (EMG), 8 (19%) had normal results.
      Fifty-one children had a muscle biopsy; the results were normal/nondiagnostic in
      10 (20%). Median time from disease onset to diagnosis was different between
      racial groups: Caucasians (n=59) 2.0 months: for minorities (n=20), 6.5 months,
      (p=0.0008). The median time from disease onset to therapy was: Caucasians. 3.0
      months; minorities, 7.2 months (p=0.002). Report of calcinosis was associated
      with increased time to diagnosis and therapy (p=0.04). In the 33 children whose
      first symptom occurred in June-September, rash preceded or accompanied onset of
      muscle weakness in 83% (n=27). Ninety-one percent of the children were given
      steroid therapy and 9% received methotrexate as well. CONCLUSION: The results of
      an undirected site for muscle biopsy or EMG may not be diagnostic. Minority
      children had a longer interval between first JDM symptom and diagnosis/therapy
      than Caucasian children. Delay in diagnosis/therapy was associated with
      calcinosis.

PMID- 9632087
TI  - Juvenile rheumatoid arthritis and common variable hypogammaglobulinemia.
AB  - We describe a 9-year-old white boy with systemic juvenile rheumatoid arthritis
      (JRA) who developed pancytopenia and hypersplenism at the age of 13 years. He
      underwent splenectomy and 3 years later he developed Coombs' positive hemolytic
      anemia, alopecia, juvenile warts, and multiple bacterial infections. At that
      time, investigations were compatible with severe hypogammaglobulinemia associated
      with common variable immunodeficiency. Concomitantly with this condition he
      experienced complete remission of his inflammatory arthritis. Immunologic studies
      of B and T lymphocyte function showed that the number of circulating T and B
      lymphocytes were normal, while T cell function was depressed, as evidenced by
      markedly reduced proliferative responses to mitogens and antigens, and ability to
      mediate B cell help. In addition, his circulating B cells were unable to secrete
      IgM or IgG. He also exhibited anergy to intradermal challenge with a battery of
      common antigens. The literature dealing with this clinical association is
      reviewed, and possible immunologic mechanisms involved are discussed.

PMID- 9632088
TI  - Severe aortic regurgitation with mechanical prosthetic valve replacement in
      pauciarticular juvenile rheumatoid arthritis.
AB  - We describe a patient with pauciarticular juvenile rheumatoid arthritis with
      aortic insufficiency who underwent successful aortic valve replacement with a
      mechanical prosthetic valve.

PMID- 9632089
TI  - Massive lymphadenopathy and airway obstruction in a child with Kawasaki disease:
      success with pulse steroid therapy.
AB  - Kawasaki disease (KD) is an acute, febrile, self-limited, multisystem vasculitis
      that almost exclusively affects young children. We describe a 4-year-old girl
      with intravenous immunoglobulin (IVIG) resistant KD who developed massive
      cervical lymphadenopathy and severe respiratory distress. Treatment with
      intravenous pulse methylprednisolone led to dramatic resolution of her symptoms.
      We conclude that pulse steroid therapy should be considered in patients with KD
      complicated by massive lymphadenopathy with life threatening airway obstruction
      and/or IVIG resistant disease.

PMID- 9632090
TI  - Pancytopenia secondary to hemophagocytic syndrome in rheumatoid arthritis treated
      with methotrexate and sulfasalazine.
AB  - Hemophagocytic syndrome is an exceptional cause of pancytopenia. Its etiologies
      are most commonly viral or bacterial infections, lymphoproliferative syndromes,
      acquired or congenital immunodeficiencies, systemic diseases, or immunomodulatory
      treatment. We describe a patient with rheumatoid arthritis (RA) treated with
      methotrexate (MTX), sulfasalazine, and low dose corticosteroids, whose case was
      seriously complicated by the occurrence of acute febrile pancytopenia. The
      pancytopenia appeared secondary to hemophagocytic syndrome triggered by
      Escherichia coli septicemia. The evolution was marked by severe aggravation of
      RA, probably due to release of cytokines from macrophages (tumor necrosis factor
      alpha, interleukin 6). Reintroduction of MTX (without sulfasalazine) resulted in
      partial remission and there was no reappearance of new hematological anomalies
      after 16 month followup. A knowledge of this syndrome is particularly important,
      since it mimics drug toxicity and other complications such as lymphoproliferative
      diseases.

PMID- 9632091
TI  - Chloroquine related cardiac toxicity.
AB  - Chloroquine, an agent used in treatment and prophylaxis of malaria, and also
      known for its antiinflammatory effects in dermatological, rheumatological, and
      connective tissue disorders, has been reported to cause toxicity, most commonly
      in the retina and the cardiovascular system. We describe a 60-year-old woman with
      longstanding rheumatoid arthritis receiving multidrug treatment, including
      prolonged administration of chloroquine. She developed complete heart block
      requiring a permanent pacemaker, congestive heart failure, and progressive
      myopathy. During hospital investigations for her myopathy, she died of acute
      pulmonary thromboembolism. Although hypertension and possibly amyloidosis were
      thought to be the cause of her cardiac disease, cardiac and skeletal muscle
      changes characteristic of chloroquine toxicity were observed. Chloroquine may be
      an important unsuspected contributing cause of cardiac dysfunction in patients
      with rheumatological disease. Endomyocardial biopsy should be considered early in
      the course of diagnosis and management.

PMID- 9632092
TI  - CD4 mononuclear cell infiltrates and Fas/Fas ligand positive mammary gland cells
      in breast tissue from a patient with Sjogren's syndrome.
AB  - We describe a 49-year-old patient with lip biopsy proven Sjogren's syndrome (SS)
      and keratoconjunctivitis sicca, who had dental caries, xerostomia, recurrent
      upper respiratory tract infections, arthritis in her hands, elbows and knees, and
      recurrent parotid inflammation. She developed bilateral breast nodules in 1988.
      Right breast nodules were excised in 1993 and 1995, but reappeared in 1996,
      requiring 2 more excisions. Breast tissue samples showed remarkable intralobular
      and perilobular mononuclear cell infiltrates that were predominantly CD4+ T cells
      and expressed bcl-2. A few cells stained CD20+ and CD8+. SS breast glandular
      epithelial cells stained more intensely for Fas compared to normal cells. CD4+ T
      cells and Fas mediated cell death may be involved in the mammary gland lesions in
      SS.

PMID- 9632093
TI  - Association of primary antiphospholipid syndrome with inherited activated protein
      C resistance.
AB  - A 65-year-old man had had arterial thromboses of the lower limbs and cerebral
      region for several years; tests revealed anticardiolipin, antiphosphatidylserine,
      anti-beta2-glycoprotein I antibodies, and lupus anticoagulant. As well, both
      phenotypic and genotypic resistance to activated protein C was found.
      Antiphospholipid antibodies have been reported to interfere in different ways
      with the functions of protein C; in our patient the simultaneous existence of
      inherited resistance to activated protein C could account for the thrombophilic
      status underlying the diffuse and serious arterial thromboses.

PMID- 9632094
TI  - Antithyroid arthritis syndrome.
AB  - We describe a recent clinical case experience of antithyroid arthritis syndrome
      and literature search from 1965 to 1996 on antithyroid medication and associated
      arthritis using MEDLINE and EMBASE. The antithyroid arthritis syndrome is a
      transient migratory polyarthritis that occurs within 2 months of starting
      thionamide treatment, and resolves within 4 weeks of stopping therapy.
      Discontinuation of medication is necessary. Alternative forms of treatment for
      hyperthyroidism should be sought. Nonsteroidal antiinflammatory drug or treatment
      of the rheumatic complaints is recommended or if unsuccessful, corticosteroid
      treatment.

PMID- 9632095
TI  - Prevalence and outcome of uveitis in a regional cohort of patients with juvenile
      rheumatoid arthritis.

PMID- 9632096
TI  - Facial pain and giant cell arteritis.

PMID- 9632097
TI  - Osteonecrosis and HIV infection: 4 more cases.

PMID- 9632098
TI  - Longterm outcomes and quality of life in juvenile RA.

PMID- 9632099
TI  - Hodgkin's disease in a patient with juvenile rheumatoid arthritis taking weekly
      low dose methotrexate.

PMID- 9632100
TI  - Toxicities of dapsone in the treatment of cutaneous manifestations of rheumatic
      diseases.

PMID- 9632101
TI  - Carotid occlusion mimicking giant cell arteritis.

PMID- 9632102
TI  - Cell cycle: molecular targets for diagnosis and therapy: tumor suppressor genes
      and cell cycle progression in cancer.
AB  - A significant portion of published literature is dedicated to describing the
      cloning and the characterization of proteins involved in the progression of the
      cell cycle, which govern cell growth both in cancer and normal ontogenesis. With
      this abundance of information, the cascading pathways of molecular events that
      occur in the cell cycle are proving to be exceedingly complicated. The purpose of
      this conference was to attract the leading clinical and basic science
      investigators in the growth control field with a final goal to determine how this
      current wealth of knowledge can be used to impact upon patient care and
      management by the design of novel adjuvant therapeutics specifically targeted at
      tumor cells and the identification of molecular diagnostic and/or prognostic
      markers in an efficient and cost effective manner.

PMID- 9632103
TI  - Analysis of activin A gene expression in human bone marrow stromal cells.
AB  - Activin A, a member of the TGF-beta superfamily, plays roles in differentiation
      and development, including hematopoiesis. Our previous studies indicated that the
      expression of activin A by human bone marrow cells and monocytes is highly
      regulated by inflammatory cytokines and glucocorticoids. The present study was
      undertaken to investigate the regulation of activin A gene expression in the
      human bone marrow stromal cell lines L87/4 and HS-5, as well as in primary
      stromal cells. Northern blots demonstrated that, like primary stromal cells, the
      cell lines expressed four activin A RNA transcripts (6.4, 4.0, 2.8, and 1.6 kb),
      although distribution of the RNA among the four sizes varied. The locations of
      the 5' ends of the RNAs were investigated by Northern blots and RNase protection
      assays. The results identified a transcription start site at 212 nucleotides
      upstream of the translation start codon. In addition, luciferase expression
      assays of a series of deletion constructs were used to identify regulatory
      sequences upstream of the activin A gene. A 58 bp upstream sequence exhibits
      promoter activity. However, severalfold higher expression requires a positive
      element consisting of an additional 71 bp of the upstream region. Promoter
      activity was also identified between 2.5 and 3.6 kb upstream of the start codon.
      These findings suggest that expression of activin A at the transcriptional level
      follows complex patterns of regulation.

PMID- 9632104
TI  - Msh homeobox genes regulate cadherin-mediated cell adhesion and cell-cell
      sorting.
AB  - Msx-1 and Msx-2 are two closely related homeobox genes expressed in cephalic
      neural crest tooth buds, the optic cup endocardial cushions, and the developing
      limb [Hill and Davidson, 1991; Monaghan et al., 1991; Robert et al., 1991]. These
      sites correspond to regions of active cell segregation and proliferation under
      the influence of epithelial-mesenchymal cell interactions [Brown et al., 1993;
      Davidson et al., 1991], suggesting that Msx-1 and Msx-2 regulate cell-cell
      interactions. We have investigated the potential relationship between expression
      of the Msh homeobox genes (Msx-1 and Msx-2) and cadherin-mediated cell adhesion
      and cell sorting. We report that cell lines stably expressing Msx-1 or Msx-2
      differentially sort on the basis of Msh gene expression. We demonstrate in vitro
      that initial cell aggregation involves calcium-dependent adhesion molecules
      (cadherins) and that Msh genes regulate cadherin-mediated adhesion. These results
      support the hypothesis that Msh genes play a role in the regulation of cell-cell
      adhesion and provide a link between the genetic phenomena of homeobox gene
      expression and cellular events involved in morphogenesis, including cell sorting
      and proliferation.

PMID- 9632105
TI  - Cloning and characterization of a Dictyostelium gene encoding a small GTPase of
      the Rab11 family.
AB  - Eukaryotic cells achieve complexity by compartmentalizing a subset of cellular
      functions into membrane-bound organelles. Maintaining this high level of cellular
      organization requires precise regulation of traffic between membranes. This task
      is accomplished, in part, by rab proteins. How these small GTPases regulate
      membrane traffic between cellular compartments is not clear. Here we report the
      characterization of a novel rab GTPase from the soil amoebae Dictyostelium
      discoideum. The predicted coding sequence of the new rab gene, Dictyostelium
      rab11b, encodes a protein of 25 kD containing all the structural hallmarks of a
      rab GTPase. Comparison of the sequence with the GenBank database and cladistic
      analysis demonstrated Dictyostelium rab11b to be a divergent member of the rab11
      branch of rab proteins. Southern analysis revealed the presence of related genes
      in Dictyostelium. RNAse protection assays showed the Dictyostelium rab11b gene to
      be expressed at uniform levels throughout growth and development. Gene deletion
      experiments revealed that Dictyostelium rab11b was not essential for growth or
      development. Conceivably, the function of rab11b may be redundant with that of
      related genes in this organism.

PMID- 9632106
TI  - Downregulation and subcellular redistribution of the gamma-aminobutyric acidA
      receptor induced by tunicamycin in cultured brain neurons.
AB  - The significance of N-linked glycosylation and oligosaccharide processing was
      examined for the expression of gamma-aminobutyric acidA receptor (GABA(A)R) in
      cultured neurons derived from chick embryo brains. Incubation of cultures with 5
      microg/ml of tunicamycin for 24 h blocked the binding of 3H-flunitrazepam and 3H
      muscimol, probes for the benzodiazepine and GABA sites on the receptor, by about
      20% and 28%, respectively. The loss of ligand binding was due to a reduction in
      the number of binding sites with no significant changes in receptor affinity.
      Light microscopic immunocytochemistry also revealed that the treatment reduced
      approximately 13% of the intensity of GABA(A)R immunoreactivity in the neuronal
      somata. Furthermore, the fraction of intracellular receptors was decreased to 24%
      from 34% of control in the presence of the agent, as revealed by trypsinization
      of cells in situ followed by 3H-flunitrazepam binding. The molecular weight of
      the receptor subunit protein was lowered around 0.5 kDa after tunicamycin
      treatment, in accordance with that following N-glycosidase F digestion,
      indicating the blockade of N-linked glycosylation of GABA(A)R by tunicamycin.
      Moreover, intense inhibitions of 91% and 44%, respectively, were detected to the
      general galactosylation and mannosylation in the tunicamycin-treated cells,
      whereas the protein synthesis was hindered by 13%, through assaying the
      incorporation of 3H-sugars and 3H-leucine. Nevertheless, treatment with
      castanospermine or swainsonine (10 microg/ml, 24 h), inhibitors to maturation of
      oligosaccharides, failed to produce significant changes in the ligand binding. In
      addition, in situ hybridization analysis showed that these three inhibitors did
      not perturb the mRNA of GABA(A)Ralpha1-subunit. The data suggest that tunicamycin
      causes the downregulation and subcellular redistribution of GABA(A)R by producing
      irregularly glycosylated receptors and modifying their localization. Both
      galactosylation and mannosylation during the process of N-linked glycosylation
      may be important for the functional expression and intracellular transport of
      GABA(A)R.

PMID- 9632107
TI  - Phosphorylation of phospholamban correlates with relaxation of coronary artery
      induced by nitric oxide, adenosine, and prostacyclin in the pig.
AB  - The intracellular mechanisms underlying the action of the endogenous vasodilators
      such as NO/EDRF, adenosine, and prostacyclin acting through cGMP and cAMP,
      respectively, are not well understood. One important action of cyclic nucleotides
      in smooth muscle relaxation is to lower the cytosolic Ca2+ concentration by
      enhanced sequestration into the sarcoplasmic reticulum. The present study was
      undertaken to elucidate the potential role of phosphorylation of phospholamban,
      the regulator of sarcoplasmic reticulum Ca2+ pump, for the control of coronary
      vascular tone by NO/EDRF, adenosine, and prostacyclin. Phospholamban was
      identified in pig coronary artery preparations by immunofluorescence microscopy,
      Western blotting and in vitro phosphorylation. Segments of pig coronary artery,
      with either intact or denuded endothelium, were precontracted with prostaglandin
      F2alpha (PGF2alpha). In endothelium-denuded preparations 3-morpholinosydnonimine
      (SIN-1), 5'-N-ethylcarboxiamidoadenosine (NECA), and iloprost (ILO) caused both
      relaxation and phospholamban phosphorylation with the potency: SIN-1 > NECA >
      ILO. The regulatory myosin light chain was significantly dephosphorylated only by
      SIN-1. In endothelium-intact pig coronary artery, L-NAME caused additional
      vasoconstriction and a decrease in phospholamban phosphorylation, while
      phosphorylation of myosin light chain remained unchanged. An inverse relationship
      between phospholamban phosphorylation and vessel tone was obtained. Our findings
      demonstrate significant phospholamban phosphorylation during coronary artery
      relaxation evoked by NO, prostacyclin, and adenosine receptor activation. Because
      of the close correlation between phosphorylation of phospholamban and vessel
      relaxation, we propose that phospholamban phosphorylation is an important
      mechanism by which endogenous vasodilators, especially endothelial NO/EDRF,
      control coronary vascular smooth muscle tone.

PMID- 9632108
TI  - Early alterations of actin cytoskeleton in OK cells by opioids.
AB  - Recently we identified and characterized opioid binding sites in OK (opossum
      kidney) cells and observed decreased proliferation of these cells in response to
      opioids. In the present study we investigated the effects of opioids on the actin
      cytoskeleton and explored whether their antiproliferative action may relate to
      alterations in the distribution or the dynamics of actin microfilaments. Exposure
      of OK cells to the opioids alphaS1 casomorphin and ethylketocyclazocine resulted
      in a rapid and substantial actin microfilament reorganization. This was
      documented by a significant dose-dependent decrease in the amounts of F-actin,
      determined by measurements of quantitative fluorescence, by immunoblot analysis
      and by a concomitant increase of the G/total-actin ratio measured by the DNase I
      inhibition assay. These changes were verified by confocal laser scanning
      microscopy, which showed marked redistribution of the microfilamentous structures
      in the presence of the opioids without affecting the organization of microtubules
      or vimentin intermediate filaments. The effect of opioids on actin polymerization
      dynamics occurred within 15 min and persisted for at least 2 h, while their
      restoration to control levels was accomplished 6 h later, indicating a reversible
      phenomenon. Northern blot analysis showed that the concentration of the actin
      transcript was unaffected. The addition of diprenorphine, a general opioid
      antagonist, prevented the effects of opioids on the actin cytoskeleton. The
      inhibition of OK cell proliferation, induced by ethylketocyclazocine and alphaS1
      casomorphin was partially prevented in the presence of phallacidin, which
      stabilizes microfilaments. Our findings demonstrate that opioids, acting via
      kappa 1 binding sites, induce rapidly modifications in the dynamics of actin
      polymerization, and in the organization of microfilaments in OK cells, which may
      relate to their antiproliferative effect on these cells.

PMID- 9632109
TI  - Transforming growth factor-beta1 induces apoptotic cell death in cultured retinal
      endothelial cells but not pericytes: association with decreased expression of
      p21waf1/cip1.
AB  - Transforming growth factor-beta1 (TGF-beta1) regulates a variety of cellular
      functions. In several types of cells, for example, it acts as a growth inhibitor
      and an inducer of apoptotic cell death. Although one of the important modulators
      in retinal vascular development and retinal neovascularization, the effects of
      TGF-beta1 on retinal microvascular cells are not fully defined. We have found
      that proliferation of both bovine retinal endothelial cells (EC) and pericytes
      was inhibited by TGF-beta1 in a concentration-dependent manner. However, only
      retinal EC lost viability after exposure to increasing concentrations of TGF
      beta1 (up to 10 microg/ml) in the presence of 2% fetal bovine serum. Dying EC
      exhibited the morphological and biochemical characteristics of apoptosis.
      Fragmented nuclei and chromatin condensation were apparent after staining with
      the fluorochrome Hoechst 33258 and the reagent ApopTag; moreover, gel
      electrophoresis of DNA from TGF-beta1-treated EC demonstrated degradation of
      chromatin into the discrete fragments typically associated with apoptosis. The
      addition of anti-TGF-beta1 neutralizing antibody abolished the apoptotic cell
      death induced by TGF-beta1. Because not all the EC in a given culture died after
      exposure to TGF-beta1, we separated the apoptosis-sensitive cells from those
      resistant to TGF-beta1 -mediated apoptosis and determined the expression of
      several proteins associated with this apoptotic pathway. Apoptosis of EC mediated
      by TGF-beta1 was associated with a decreased level of the cyclin-dependent kinase
      inhibitor p21waf1/cip1, compared with that observed in the apoptosis-resistant
      cells. In contrast, the translation product of the tumor-suppressor gene p53 was
      increased in the TGF-beta1-treated apoptotic cells. Thus, we propose that
      p21waf1/cip1 and p53 function in distinct pathways that are protective or
      permissive, respectively, for the apoptotic signals mediated by TGF-beta1.

PMID- 9632110
TI  - Estrogen stimulates PTHrP but not PTH/PTHrP receptor gene expression in the
      kidney of ovariectomized rat.
AB  - The aim of the present study was to test the hypothesis that the decreased renal
      tubular reabsorption of calcium observed in estrogen deficiency is associated
      with a local regulation of either PTHrP or PTH/PTHrP receptor genes in the
      kidney. Rats were randomly sham-operated (S) or ovariectomized receiving either
      vehicle (OVX) or 4 microg E2/kg/day (OVX+E4) or 40 microg E2/kg/d (OVX+E40)
      during 14 days using alzet minipumps. Plasma PTH and calcium levels were lower in
      untreated OVX animals than in all other groups (P < 0.01). Plasma PTH was higher
      in OVX+E40 than in OVX+E4 (P < 0.05). PTHrP mRNA expression in the kidney was
      unaffected by ovariectomy but was increased in OVX+E40 (0.984 +/- 0.452 for
      PTHrP/GAPDH mRNAs expression vs. 0.213 +/- 0.078 in sham, P < 0.01). PTH/PTHrP
      receptor mRNA expression and the cAMP response of renal membranes to PTH were
      unaffected by ovariectomy and estrogen substitution. In conclusion, renal PTHrP
      and PTH/PTHrP receptor mRNAs are not modified by ovariectomy. However, 17beta
      estradiol increases renal expression of PTHrP mRNA without evident changes in its
      receptor expression and function. This may help to explain the pharmacological
      action of estrogen in the kidney, especially how it prevents the renal leak of
      calcium in postmenopausal women.

PMID- 9632111
TI  - Novel nuclear localization signal between the two DNA-binding zinc fingers in the
      human vitamin D receptor.
AB  - The human vitamin D receptor (hVDR) possesses a unique array of five basic amino
      acids positioned between the two DNA-binding zinc fingers that is similar to well
      characterized nuclear localization sequences in other proteins. When residues
      within this region are mutated to nonbasic amino acids, or when this domain is
      deleted, the receptor is still well expressed, but it no longer associates with
      the vitamin D-responsive element in DNA, in vitro, and hVDR-mediated
      transcriptional activation is abolished in transfected cells. Concomitantly, the
      mutated hVDRs exhibit a significant shift in hVDR cellular distribution favoring
      cytoplasmic over nuclear retention as assessed by subcellular fractionation and
      immunoblotting. Independent immunocytochemical studies employing a VDR-specific
      monoclonal antibody demonstrate that mutation or deletion of this basic domain
      dramatically attenuates hVDR nuclear localization in transfected COS-7 cells.
      Although wild-type hVDR is partitioned predominantly to the nucleus in the
      absence of the 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) hormone, treatment with
      ligand further enhances nuclear translocation, as it does to some degree in
      receptors with the basic region altered. The role of 1,25(OH)2D3 may be to
      facilitate hVDR heterodimerization with retinoid X receptors, stimulating
      subsequent DNA binding and ultimately enhancing nuclear retention. Taken
      together, these data reveal that the region of hVDR between Arg-49 and Lys-55
      contains a novel constitutive nuclear localization signal, RRSMKRK.

PMID- 9632112
TI  - Characterization of naturally occurring myosin heavy chain antisense mRNA in rat
      heart.
AB  - Analysis of mRNA by Northern blot and reverse transcription-polymerase chain
      reaction demonstrated the expression of sense and considerable amounts of
      naturally occurring antisense mRNA for beta-myosin heavy chain (MHC) and alpha
      MHC in the neonatal rat heart: antisense MHC mRNA expression of alpha-MHC and
      beta-MHC was approximately half of the corresponding sense MHC mRNA expression.
      Using a computational approach, we could identify a reverse Pol II promoter in
      the beta-MHC gene. Both sense and antisense MHC mRNA demonstrated similar sizes
      of approximately 6,000 bp in the Northern blot. Alpha-MHC antisense mRNA
      consisted of approximately 3,700 bp of complementary exon sequences and beta-MHC
      consisted of approximately 2,700 bp, suggesting a higher probability of alpha-MHC
      mRNA dimerization. Hence, sense mRNA transcripts and protein of alpha-MHC should
      exist at different relative levels in the neonatal state. In fact, the relative
      proportion of alpha-MHC was 52.0 +/- 2.6% on the sense mRNA but only 36.3 +/-
      1.8% on the protein level. Because of its high abundance in the heart, we suggest
      that in the neonatal heart naturally occurring antisense mRNA may play a role in
      the regulation of MHC expression and, therefore, in the control of the
      energetical and contractile behaviour of the heart.

PMID- 9632113
TI  - Gene expression of monocyte chemoattractant protein-1 in giant cell tumors of
      bone osteoclastoma: possible involvement in CD68+ macrophage-like cell migration.
AB  - Giant cell tumor of bone (GCT) is one of a few neoplasms in which the
      macrophage/osteoclast precursor cells and osteoclast-like giant cells infiltrate
      the tumor mass. Monocyte chemoattractant protein 1 (MCP-1) is a potent
      chemotactic factor specific for monocytes. In search of relevant cytokines that
      may enhance the recruitment of these reactive cells, we evaluated the
      localization and regulation of MCP-1 mRNA and protein in GCT by using Northern
      blot analysis, in situ hybridization and immunohistochemistry. We also determined
      whether conditioned medium obtained from GCT cultures can recruit human
      peripheral blood monocytes (CD68+) in an in vitro chemotactic assay. Using
      Northern blot analysis, we detected the specific gene transcript for MCP-1 in all
      GCT samples tested. In situ hybridization and immunohistochemistry revealed that
      both MCP-1 gene transcript and protein were consistently present in the cytoplasm
      of stromal-like tumor cells of GCT. Treatment of mononuclear cells from GCT at
      third passage with TGF-beta1 for 24 h increased the level of MCP-1 mRNA in a dose
      dependent manner, with the maximum effect at 1 ng/ml. Conditioned media from GCT
      cultures promoted the chemotactic migration of CD68+ peripheral monocytes, an
      activity which was abolished by the addition of MCP-1 antibody to the conditioned
      medium. Thus, the results of this study suggest that recruitment of CD68+
      macrophage-like cells may be due to the production MCP-1 by stromal-like tumor
      cells. These CD68+ cells may originate from peripheral blood and could have the
      capability of further differentiating into osteoclasts in the tumor.

PMID- 9632114
TI  - Ras-associated nuclear structural change appears functionally significant and
      independent of the mitotic signaling pathway.
AB  - An altered nuclear morphology has been previously noted in association with Ras
      activation, but little is known about the structural basis, functional
      significance, signaling pathway, or reproducibility of any such change. We first
      tested the reproducibility of Ras-associated nuclear change in a series of rodent
      fibroblast cell lines. After independently developing criteria for recognizing
      Ras-associated nuclear change in a Papanicolaou stained test cell line with an
      inducible H(T24)-Ras oncogene, two cytopathologists blindly and independently
      assessed 17 other cell lines. If the cell lines showed Ras-associated nuclear
      change, a rank order of increasing nuclear change was independently scored. Ras
      associated nuclear changes were identified in v-Fes, v-Src, v-Mos, v-Raf, and
      five of five H(T24)-Ras transfectants consisting of a change from a flattened,
      occasionally undulating nuclear shape to a more rigid spherical shape and a
      change from a finely textured to a coarse heterochromatic appearance. Absent or
      minimal changes were scored in six control cell lines. The two cytopathologists'
      independent morphologic rank orders were similar (P < .0002). The mitogen
      signaling pathway per se does not appear to transduce the change since no
      morphologic alterations were identified in cell lines with activations of
      downstream components of this pathway--MAPKK or c-Myc--and the rank orders did
      not correlate with markers of mitotic rate (P > .11). The rank order correlated
      closely with metastatic potential (P < .0014 and P < .0003) but not with histone
      H1 composition or global nuclease sensitivity. Based on published studies of five
      of the cell lines, there may be a correlation between increases in certain
      nuclear matrix proteins and the Ras-associated nuclear change.

PMID- 9632116
TI  - The demand and financial cost of hospital care for diabetes mellitus and its
      related complications.

PMID- 9632115
TI  - Regulation of endothelial cell myosin light chain phosphorylation and
      permeability by vanadate.
AB  - The involvement of tyrosine protein phosphorylation in the regulation of
      endothelial cell (EC) contraction and barrier function is poorly understood. We
      have previously shown that myosin light chain (MLC) phosphorylation catalyzed by
      a novel 214 kDa EC myosin light chain kinase (MLCK) isoform is a key event in EC
      contraction and barrier dysfunction [Garcia et al. (1995): J Cell Physiol 163:510
      522; Garcia et al. (1997): Am J Respir Cell Mol Biol 16:487-491]. In this study,
      we tested the hypothesis that tyrosine phosphatases participate in the regulation
      of EC contraction and barrier function via modulation of MLCK activity. The
      tyrosine phosphatase inhibitor, sodium orthovanadate (vanadate), significantly
      decreased electrical resistance across bovine EC monolayers and increased albumin
      permeability consistent with EC barrier impairment. Vanadate significantly
      increased EC MLC phosphorylation in a time-dependent manner (maximal increase
      observed at 10 min) and augmented both the MLC phosphorylation and permeability
      responses produced by thrombin, an agonist which rapidly increases tyrosine
      kinase activities. The vanadate-mediated increase in MLC phosphorylation was not
      associated with alterations in either phosphorylase A Ser/Thr phosphatase
      activities or in cytosolic [Ca2+] but was strongly associated with significant
      increases in EC MLCK phosphotyrosine content. These data suggest that tyrosine
      phosphatase activities may participate in EC contractile and barrier responses
      via the regulation of the tyrosine phosphorylation status of EC MLCK.

PMID- 9632117
TI  - Seventy-five years ago: insulin treatment in Hereford General Hospital.
AB  - This year, 1998, marks the 75th anniversary of the general availability of
      insulin in the United Kingdom. To mark the occasion, Diabetic Medicine publishes
      this account of the early days of insulin therapy in one of Britain's district
      general hospitals, Hereford General Hospital. The authors describe the first
      tentative use of insulin and draw some interesting parallels with the issues
      which still concern the introduction of novel therapies in endocrinology today.

PMID- 9632118
TI  - Immunochemical quantification of crossline as a fluorescent advanced glycation
      endproduct in erythrocyte membrane proteins from diabetic patients with or
      without retinopathy.
AB  - Crossline is a novel advanced glycation endproduct (AGE) which has both a
      crosslink and fluorescence similar to AGE-protein in vivo. To assess the
      association of AGEs to the development of diabetic retinopathy we developed a
      sensitive and specific enzyme-linked immunosorbent assay (ELISA) for crossline in
      blood samples and investigated the association of the development of retinopathy
      and erythrocyte membrane protein (EMP)-crossline concentrations in patients with
      Type 2 diabetes mellitus (Type 2 DM). Crossline formation in EMP exceeded that in
      haemoglobin and was detectable in normal EMP samples without pretreatment by this
      ELISA system. Mean (+/-SE) EMP crossline levels were elevated 1.6-fold in
      diabetic patients without retinopathy (7.6 +/- 0.5 pmol mg(-1), p < 0.005), 2.2
      fold in diabetic patients with non-proliferative retinopathy (10.5 +/- 0.6 pmol
      mg(-1), p < 0.001) and 2.6-fold in diabetic patients with proliferative
      retinopathy (12.0 +/- 0.6 pmol mg(-1), p < 0.001) compared with healthy control
      subjects (4.7 +/- 0.5 pmol mg(-1)). Type 2 DM patients with retinopathy had
      significantly higher EMP-crossline levels than those without retinopathy (p <
      0.005). Our data suggest that elevated EMP-crossline concentrations are
      associated with the presence of retinopathy in patients with Type 2 DM and EMP
      crossline measured by our ELISA may provide a useful marker for assessing the
      role of glycation in the development of diabetic retinopathy.

PMID- 9632119
TI  - Impaired vasoconstriction of peripheral cutaneous blood flow in Type 1 diabetic
      patients following food ingestion.
AB  - Abnormalities in cutaneous blood flow (CBF) in otherwise healthy subjects with
      Type 1 diabetes mellitus (DM) have been demonstrated in response to local insults
      to the skin. To investigate whether defects also occurred in response to a
      regular daily activity, CBF was measured with laser Doppler flowmetry (LDF),
      before and 20 min after starting a mixed meal in 13 male Type 1 DM subjects with
      no clinical evidence of neuropathy, nephropathy or macroangiopathy and compared
      to 7 non-diabetic controls. Diabetic subjects and controls were of similar age
      and body mass index (mean +/- SD, 33.7 +/- 7.4 vs 37.1 +/- 9.2 years and 25.2 +/-
      2.9 vs 24.5 +/- 2.9 kg m(-2), respectively). In subjects with DM, HbA1c was 8.3
      +/- 0.6% (normal range 4-5.5%) and duration of diabetes was 18 (8-38) years,
      median (range). Following a mixed meal the CBF fell in the controls by 36% (24 to
      56), median (range), compared to 3% (-5 to 18) in Type 1 DM subjects, P < 0.0005.
      These results show there is a normal physiological fall in CBF following food
      ingestion which is attenuated in Type 1 DM. These abnormalities of
      vasoconstriction in the peripheral microcirculation are present after 8 years of
      diabetes and precede the development of clinically apparent neuropathy or
      vascular disease.

PMID- 9632120
TI  - Evidence for specific autoimmunity against sympathetic and parasympathetic
      nervous tissues in Type 1 diabetes mellitus and the relation to cardiac autonomic
      dysfunction.
AB  - There is growing evidence for the involvement of immunological factors in the
      pathogenesis of cardiac autonomic dysfunction in Type 1 diabetes mellitus (DM).
      To evaluate the presence of autoantibodies against autonomic nervous tissues and
      their relationship with tests of autonomic function, 64 newly diagnosed and 142
      long duration Type 1 DM patients were investigated for sympathetic and
      parasympathetic ganglia (CF-SG and CF-PSG) autoantibodies with a complement
      fixing indirect immunofluorescence technique. Five cardiac reflex tests were
      performed to assess autonomic function. Fifty-seven patients with neurological
      diseases other than diabetic neuropathy and 131 healthy control subjects were
      also tested for CF-SG and CF-PSG autoantibodies. CF-SG autoantibodies were
      observed in 47 (23%) and CF-PSG autoantibodies in 21 (10%) of 206 Type 1 DM
      patients (p < 0.001). In contrast, these autoantibodies were detected in 3 (5%)
      and 1 (2%) of patients with non-diabetic neurological diseases and 3 (2%) and 4
      (3%) of control subjects (p < 0.01, p < 0.05, p < 0.0001, p < 0.05 vs Type 1 DM
      patients). All except two Type 1 DM patients with CF-PSG autoantibodies also
      presented with CF-SG autoantibodies. In diabetic patients with long duration, CF
      SG autoantibodies were more frequent in patients with ECG-based cardiac autonomic
      neuropathy (CAN; > or =2 of 5 cardiac reflex tests abnormal) compared to patients
      without CAN although this did not reach statistical significance (29% vs 17%, p =
      0.06). However, 4 (80%) of 5 newly diagnosed and 23 (32%) of 73 established Type
      1 DM patients with abnormalities in heart rate variation during deep breathing
      and/or standing from lying presented with CF-SG autoantibodies compared to 12
      (25%) of 58 newly diagnosed (p < 0.05) and 7 (11%) of 63 established Type 1 DM
      patients (p < 0.01), in whom both tests were normal. The results suggest that
      autoimmune factors contribute to the pathogenesis of cardiac autonomic
      dysfunction in Type 1 DM and that autoantibodies against sympathetic and
      parasympathetic nervous tissues are relatively specific for Type 1 DM.

PMID- 9632121
TI  - Serum sex-hormone-binding globulin is related to hepatic and peripheral insulin
      sensitivity but not to beta-cell function in men and women with Type 2 diabetes
      mellitus.
AB  - This study examined the relationship of hepatic and peripheral insulin
      sensitivity and beta-cell secretory function with serum sex hormone-binding
      globulin (SHBG) in men and women with Type 2 diabetes mellitus (DM). Fasting
      insulin, glucose and SHBG were measured in 58 Type 2 diabetic patients of both
      sexes (36 men) who were on diet treatment only and terms for insulin sensitivity
      and beta-cell secretion obtained by modelling. There was no significant
      difference in SHBG between men and women despite similar degree of obesity. SHBG
      was positively correlated (r = 0.41, p < 0.01) to hepatic insulin sensitivity
      derived from mathematical modelling of fasting glucose and insulin data using the
      homeostasis assessment model (HOMA). This relationship was independent of gender
      (men, r = 0.48, p < 0.01; women, r = 0.45, p < 0.05). Fasting insulin correlated
      negatively with SHBG in men (r = -0.34, p < 0.05). There were also significant
      negative correlations between SHBG and either plasma glucose (r = -0.29, p <
      0.05) or body mass index (r = -0.34, p < 0.05). SHBG did not correlate with HOMA
      modelled beta-cell function. In a multiple regression analysis, SHBG was
      independently correlated only with insulin sensitivity (p < 0.05). Further
      studies in 15 of the diabetic patients (11 men), showed a significant positive
      correlation (r = 0.52, p < 0.05) between SHBG and peripheral insulin sensitivity
      derived by continuous infusion of glucose with model assessment (CIGMA) but not
      between SHBG and CIGMA-modelled beta-cell function. These results indicate that
      both hepatic and peripheral insulin sensitivity are similarly related to serum
      SHBG in Type 2 diabetes of both sexes. The sex-difference in SHBG was abolished
      in the patients.

PMID- 9632122
TI  - Plasma leptin is not associated with insulin resistance and proinsulin in non
      diabetic South Asian Indians.
AB  - In an earlier study, we observed only a weak association between plasma insulin
      (non-specific assay) and leptin in South Asian Indians. This was in contrast to
      the observations in many other ethnic groups. With the availability of
      measurements of specific insulin (SI) and proinsulin (PI) in the same study
      group, we have reanalysed the data to look for possible correlation of leptin
      with proinsulin and with insulin resistance calculated from the fasting values of
      specific insulin and glucose using the HOMA model. Subjects with normoglycaemia
      (n = 117) and impaired glucose tolerance (n = 27, WHO criteria) were included in
      the analysis. Leptin values were higher in women. Multiple linear regression
      analysis showed that the variations in leptin concentrations in men were
      associated with BMI, WHR, and 2 h SI values (R2 = 56.2%) while fasting SI and
      proinsulin concentrations had no significant association. In women BMI and age
      showed a significant association with serum leptin values (R2 = 40.1%).
      Univariate and multivariate analyses using insulin resistance as the dependent
      variable showed that it had no association with leptin in both genders. Leptin
      had no correlation with proinsulin also. This study confirmed that in Asian
      Indians the association between plasma leptin and insulin concentrations is weak
      and that leptin has no influence on insulin resistance. Proinsulin and leptin are
      also not correlated in this population. Insulin resistance shows correlation with
      the beta-cell function both in men and women.

PMID- 9632124
TI  - Documented symptomatic hypoglycaemia in children and adolescents using multiple
      daily insulin injection therapy.
AB  - Symptomatic episodes of documented hypoglycaemia were characterized with the aid
      of a 3-month diary in a single-centre, unselected group of 161 children and
      adolescents with Type 1 diabetes mellitus, treated mainly (81%) with multiple
      dose insulin therapy. Patients and families were asked to write in the diary all
      the symptomatic episodes in which blood glucose concentration proved to be < or
      =3 mmol l(-1) before treatment. Of the patients, 83 (52%) had a total of 287
      hypoglycaemic episodes (0.6 attack per month per patient). The majority of the
      attacks, 221 (77%), were mild (patients > or =6 years able to treat themselves).
      Only two attacks were severe, resulting in coma and/or convulsion. The most
      common dominant symptoms were weakness (29%), tremor (20%), hunger (14%), and
      drowsiness (12%). Of all the dominant symptoms, 39% were classified as autonomic,
      20% neuroglycopenic, and 41% non-specific. In children under 6 years, autonomic
      symptoms were less common than in adolescents 15 years or over (34% vs 57%, p =
      0.01). In conclusion, the incidence of documented symptomatic hypoglycaemia was
      low. The symptoms were more often neuroglycopenic or non-specific than autonomic,
      especially in young children.

PMID- 9632123
TI  - Prolonged and enhanced secretion of glucagon-like peptide 1 (7-36 amide) after
      oral sucrose due to alpha-glucosidase inhibition (acarbose) in Type 2 diabetic
      patients.
AB  - GLP-1, an incretin hormone of the enteroinsular axis with insulinotropic and
      glucagonostatic activity, is secreted after nutrient ingestion. GLP-1 is mainly
      produced by intestinal L-cells in the lower gastrointestinal tract (GIT); simple
      carbohydrates are absorbed in the upper GIT and alpha-glucosidase inhibition
      leads to augmented and prolonged GLP-1 release in normal subjects. In a cross
      over study, 100 mg acarbose or placebo was administered simultaneously with 100 g
      sucrose to 11 hyperglycaemic Type 2 diabetic patients poorly controlled with diet
      and sulphonylureas. Plasma levels of GLP-1, insulin, C-peptide, glugacon, GIP,
      glucose and H2-exhalation were measured over 6 h. Differences in the integrated
      responses over the observation period were evaluated by repeated measurement
      analysis of variance with fasting values used as covariates. With acarbose,
      sucrose reached the colon 60-90 min after ingestion as indicated by a significant
      increment in breath hydrogen exhalation (p = 0.005). After an early GLP-1
      increment 15 min after sucrose under both conditions, GLP-1 release was prolonged
      in the acarbose group (p = 0.001; significant from 210 to 360 min.). Initially (0
      150 min), glucose (p = 0.001), insulin (p = 0.001), and GIP (p < 0.001) were
      suppressed by acarbose, whereas later there were no significant differences.
      Glucagon levels were higher with acarbose in the last 3 h of the 6 h observation
      period (p = 0.02). We conclude that in hyperglycaemic Type 2 diabetic patients,
      ingestion of acarbose with a sucrose load leads to elevated and prolonged GLP-1
      release.

PMID- 9632125
TI  - The comparison of four weight reduction strategies aimed at overweight patients
      with diabetes mellitus: four-year follow-up.
AB  - Weight change and glycaemic control in 132 diabetic patients previously treated
      for 1 year by four different methods aimed at weight loss were reanalysed 4 years
      after the outset. The four treatment groups comprised clinic visits, home visits,
      behavioural group therapy, and dexfenfluramine given for the initial 3 months
      followed by clinic visits. When analysed on an intention to treat basis only the
      dexfenfluramine group maintained a significant weight loss at year 4 (mean -2.46
      kg) with 43% of patients losing 3 kg or more; HBA1c was not decreased. The other
      treatment groups showed overall weight regain from year 1 to year 4. Within the
      home visit group however, the number of patients losing at least 3 kg doubled
      between years 1 (21%) and 4 (38%). When analysed on a completion basis, weight
      loss in the dexfenfluramine group was significant in females but not in males at
      year 4. During the 4 years of observation a cohort of 54 patients reflecting our
      routine clinic practice gained on average 0.35 kg. Although now withdrawn, the
      use of an appetite suppressant dexfenfluramine for just 3 months would appear to
      have a long-term advantage on weight loss in this diabetic population, although
      the weight lost was not associated with improvement in glycaemic control.

PMID- 9632126
TI  - Oral magnesium supplementation in insulin-requiring Type 2 diabetic patients.
AB  - Oral magnesium (Mg) supplementation can improve insulin sensitivity and secretion
      in patients with Type 2 diabetes mellitus (DM). We studied the effect of Mg
      supplementation on glycaemic control, blood pressure, and plasma lipids in
      insulin-requiring patients with Type 2 DM. Fifty moderately controlled patients
      were randomized to 15 mmol Mg or placebo daily for 3 months. Plasma Mg, glucose,
      HbA1c, lipids, erythrocyte Mg, Mg and glucose concentrations in 24-h urine, and
      systolic and diastolic pressure were measured before and after 3 months
      treatment. Plasma Mg concentration was higher after supplementation than after
      placebo (0.82 +/- 0.07 vs 0.78 +/- 0.08 mmol l(-1), p < 0.05), as was Mg
      excretion (5.5 +/- 1.9 vs 3.7 +/- 1.4 mmol 24 h(-1), p = 0.004) but erythrocyte
      Mg concentrations were similar. No significant differences were found in
      glycaemic control (glucose: 10.7 +/- 3.8 vs 11.6 +/- 6.2 mmol l(-1), p = 0.8;
      HbA1c: 8.9 +/- 1.6 vs 9.1 +/- 1.2%, p = 0.8), lipids or blood pressure. On
      treatment analysis (34 patients: 18 on Mg, 16 on placebo) yielded similar
      results. An increase in plasma Mg concentration irrespective of medication was
      associated with a tendency to a decrease in diastolic pressure (increased plasma
      Mg vs no increase: -4.0 +/- 10.1 vs +2.5 +/- 12.0 mmHg, p = 0.059). Three months'
      oral Mg supplementation of insulin-requiring patients with Type 2 DM increased
      plasma Mg concentration and urinary Mg excretion but had no effect on glycaemic
      control or plasma lipid concentrations.

PMID- 9632127
TI  - Guidelines for the diagnosis and outpatient management of diabetic peripheral
      neuropathy.
AB  - Guidelines on the out-patient management of diabetic peripheral neuropathy have
      been developed from an international consensus meeting attended by
      diabetologists, neurologists, primary care physicians, podiatrists and diabetes
      specialist nurses. A copy of the full document follows this summary (Appendix 1).
      The document arose out of suggestions from Neurodiab, a subgroup of the European
      Association for the Study of Diabetes, that there was a need for guidelines
      developed by consensus, for the outpatient management of patients with diabetic
      neuropathy. An international consensus group was created, chaired by two of the
      authors. A pilot working party met in 1995, followed by a full working party of
      39 experts, neurologists and diabetes physicians (Appendix 2). This compiled a
      draft guideline document which was circulated to a number of international
      bodies. After consultation with its members, the final guidelines were approved
      by Neurodiab (chairman F.A. Gries) towards the end of 1997.

PMID- 9632128
TI  - Simultaneous onset of type 1 diabetes mellitus in identical infant twins with
      enterovirus infection.
AB  - This report describes classical Type 1 insulin deficient diabetes mellitus (DM)
      arising in twins aged 14 months, both of whom had evidence of enterovirus
      infection. The diagnosis of Type 1 DM was made in the second twin within 12 days
      of the first. Enterovirus infection was detected in each twin at diagnosis by
      polymerase chain reaction (PCR). Both twins were negative for enterovirus by PCR
      5 months following diagnosis, although both were then positive for islet cell
      antibodies. Sequencing of the amplicons produced by PCR suggested that the
      viruses from each twin were not the same but that they were both variants related
      to echovirus 6.

PMID- 9632130
TI  - Long-term ACE inhibitor therapy in diabetic nephropathy: potential hazard?

PMID- 9632129
TI  - Running shoes for relief of plantar pressure in diabetic patients.
AB  - There is a causal relationship between diabetic foot ulceration, elevated plantar
      pressure, and severe sensory neuropathy. Cushioned footwear intended to relieve
      plantar pressure is well established for prevention and healing of plantar
      ulcers. The aim of the present study was to investigate whether pressure relief
      by means of a running shoe with optimized forefoot pressure damping is comparable
      to that of a custom-made soft insole placed into an in-depth shoe. The in-shoe
      pressures were compared to an in-depth shoe with the original cork insole and
      with a leather-soled Oxford shoe. The maximum reduction of plantar pressure in
      the running shoe was 47% under the 2nd and 3rd metatarsal heads, 29% at the first
      metatarsal head, and 32% at the great toe in comparison to the Oxford shoe. This
      was surpassed only by the custom-made insole, which reduced pressures at the
      metatarsal heads by 50%. The specially designed running shoe yielded the same
      pressure relief at the central metatarsal heads as the custom-made insole. Such
      shoes are likely to be very useful in preventing diabetic foot ulceration in high
      risk patients as a comparatively affordable and immediately available device.

PMID- 9632131
TI  - Radio emissions and Accutrend malfunction.

PMID- 9632132
TI  - Do radio emissions cause Accutrend to malfunction?

PMID- 9632133
TI  - Ras, but not Src, transformation of RIE-1 epithelial cells is dependent on
      activation of the mitogen-activated protein kinase cascade.
AB  - Src transformation of NIH3T3 mouse fibroblasts has been shown to be dependent on
      Ras function. Since we recently showed that the signaling pathways that mediate
      Ras transformation of RIE-1 rat intestinal epithelial cells are distinct from
      those that cause Ras transformation of fibroblasts, we utilized three approaches
      to determine if Src transformation of RIE-1 cells is dependent on Ras. First,
      although both Ras and Src cause upregulation of an epidermal growth factor (EGF)
      receptor-dependent autocrine growth loop, only Ras transformation required this
      activity. Second, whereas both Src and Ras caused upregulation of the p42 and p44
      mitogen-activated protein kinases (MAPKs), only Ras transformation was blocked by
      the inhibition of MAPK activation by treatment with the PD 98059 MEK inhibitor.
      Third, treatment with the farnesyltransferase inhibitor FTI-277 blocked Ras, but
      not Src, transformation. Taken together, these observations suggest that Src
      transformation of RIE-1 cells is not dependent on Ras. Finally, we determined
      that Ras activation of Raf-independent pathways alone is sufficient to cause
      growth transformation of RIE-1 cells. Thus, both Ras and Src cause transformation
      of RIE-1 cells via pathways distinct from those required to cause transformation
      of NIH3T3 cells.

PMID- 9632134
TI  - Cytoplasmic displacement of cyclin E-cdk2 inhibitors p21Cip1 and p27Kip1 in
      anchorage-independent cells.
AB  - Loss of attachment to an extracellular matrix substrate arrests the growth of
      untransformed cells in the G1 phase. This anchorage-dependent cell cycle arrest
      is linked to increased expression of the p21Cip1 (p21) and p27Kip1 (p27) cyclin
      dependent kinase inhibitors. The result is a loss of cdk2-associated kinase
      activity, especially that of cyclin E-cdk2. The levels of p21 and p27 are also
      upregulated in unattached transformed cells, but cyclin E-cdk2 activity remains
      high, and the cells are able to grow in an anchorage-independent manner.
      Increased expression of cyclin E and cdk2 appears to be partially responsible for
      the maintenance of cyclin E-cdk2 activity in transformed cells. To explore
      further the regulation of cyclin E-cdk2 in transformed cells, we have analysed
      the subcellular distribution of cyclin-cdk complexes and their inhibitors in
      normal human fibroblasts, their transformed counterparts, and in various human
      tumor cell lines. In substrate-attached normal fibroblasts, cyclin E and cdk2
      were exclusively in the nuclear fraction, associated with one another. When
      normal fibroblasts were detached and held in suspension, cyclin E-cdk2 complexes
      remained nuclear, but were now found associated with the p21 and p27 cdk
      inhibitors and lacked histone H1 phosphorylating activity. In contrast, the
      transformed fibroblasts and tumor cells, which are anchorage-independent, had
      more than half of their cyclin E, cdk2, p21 and p27 in the cytoplasmic fraction,
      both in attached and suspended cultures. The cytoplasmic p21 and p27 were bound
      to cyclin E-cdk2, as well as to complexes containing cyclin A and cyclin D. The
      nuclear cyclin E-cdk2 complexes from the transformed cells grown in suspension
      contained only low levels of p21 and p27 and had histone H1 kinase activity.
      Thus, at least three mechanisms contribute to keeping cyclin E-cdk2 complexes
      active in suspended anchorage-independent cells: cyclin E and cdk2 are
      upregulated, as reported previously, cdk inhibitors are sequestered away from the
      nucleus by cytoplasmic cyclin-cdk complexes, and the binding of the inhibitors to
      nuclear cyclin E-cdk2 complexes is impaired.

PMID- 9632135
TI  - Flt-1, a receptor for vascular endothelial growth factor, has transforming and
      morphogenic potentials.
AB  - A paradox of Flt-1, a tyrosine kinase receptor for vascular endothelial growth
      factor (VEGF), is that the ligand cannot activate the receptor to stimulate
      growth of cells that exogenously overexpress the receptor. In order to find Flt-1
      kinase-dependent biological systems, we obtained for the first time activated
      forms of the Flt-1 kinase in a ligand-independent manner. Replacement of the ABL
      sequences in the human leukemia oncoprotein BCR-ABL with the cytoplasmic domain
      of Flt-1 (BCR-FLT) followed by a retroviral random mutagenesis scheme gave
      constitutively active artificial chimera BCR-FLTm with mutations within the Flt-1
      sequence. Like BCR-ABL it could, but not the original BCR-FLT, transform Rat1
      fibroblasts, abrogate cytokine dependence in Ba/F3 cells, and induce neurite-like
      structures in neuronal PC12 cells. Interestingly, Rat1 cells transformed by BCR
      FLTm formed tube-like structures in basement membrane matrix. BCR-FLTm
      retroviruses may be a very useful tool to investigate an as yet uncovered
      functions of the Flt-1 kinase.

PMID- 9632136
TI  - Activation of Ras and its downstream extracellular signal-regulated protein
      kinases by the CDC25 homology domain of mouse Son-of-sevenless 1 (mSos1).
AB  - A fragment consisting of residues 584-1071 of the mouse Son-of-sevenless 1
      (mSos1) protein was found to be sufficient for stimulation of the guanine
      nucleotide exchange of Ras in vitro, which defines the CDC25 homology (CDC25H)
      domain of mSos1. Furthermore, we found that the CDC25H-domain fragment activated
      the extracellular signal-regulated protein kinases (ERKs), and was mainly
      membrane localized, when expressed in unstimulated human embryonic kidney 293
      cells. Then, we examined the roles of other mSos1 domains in autoinhibition of
      the CDC25H-domain functions in unstimulated cellular environments. First, longer
      fragments that have the CDC25H domain and the following proline-rich Grb2-binding
      domain exhibited negligible membrane localization, and accordingly much lower ERK
      activation activities, under serum-starved conditions. On the other hand, the
      preceding Pleckstrin-homology (PH) domain affects neither the ERK-activation
      activity nor the membrane-localization activity of the CDC25H domain. By
      contrast, the cells expressing a fragment containing the Dbl homology (DH) domain
      in addition to the PH and CDC25H domains exhibited remarkably low ERK activities
      under serum-starved conditions. This autoinhibitory effect of the DH domain on
      the CDC25H-domain function was shown to be relieved when cells were stimulated
      with epidermal growth factor. The DH-domain extension affected neither the in
      vitro guanine nucleotide exchange activity nor the membrane-localization activity
      of the CDC25H domain. Therefore, one of the roles of the DH domain is to exert an
      autoinhibition over the CDC25H-domain function on the cell membrane, in the
      absence, but not in the presence, of extracellular stimuli.

PMID- 9632137
TI  - Subcellular localization of the oncoprotein MTG8 (CDR/ETO) in neural cells.
AB  - The t(8;21) translocation associated with acute myeloid leukemia (AML) disrupts
      two genes, the AML1 gene also known as the core binding factor A2 (CBFA2) on
      chromosome 21, and a gene on chromosome 8, hereafter referred to as MTG8, but
      also known as CDR and ETO. Extensive information is available on AML1, a member
      of the CBF family of transcription factors, containing a highly conserved domain,
      the runt box, of the Drosophila segmentation gene runt. This gene is essential
      for the hematopoietic development and is found disrupted in several leukemias. In
      contrast, the function of the MTG8 gene is poorly understood. The predicted
      protein sequence shows two unusual, putative zinc-fingers, three proline-rich
      regions, a PEST domain and several phosphorylation sites. In addition, we found a
      region encompassing aa 443-514 predicted to have a significant propensity to form
      coiled coil structures. MTG8 displays a high degree of similarity with nervy, a
      homeotic target gene of Drosophila, expressed in the nervous system. Human and
      mouse wild-type MTG8 are also highly expressed in brain relative to other
      tissues. For these reasons, we set out to investigate the expression and
      subcellular localization of the MTG8 protein in neural cells. Immunohistochemical
      experiments in a 12.5-day-old mouse embryo clearly showed that the protein was
      expressed in the neural cells of the developing brain and the spinal cord. In
      primary cultures of hippocampal neurons of 2-3 day-old mice, MTG8 was found in
      the nucleus, in the cytoplasm and as fine granules in the neurites. Cytoplasmic
      localization of the protein was observed in Purkinje cells of both human and
      mouse cerebellum. The molecular mass of MTG8 in total human and mouse brain was
      analysed by immunoblotting and determined to be between 70 and 90 kDa. Isoforms
      with the same molecular mass were demonstrated in synaptosomes isolated from
      mouse forebrain. The evidence of MTG8 in the nucleus and cytoplasm of neural
      cells suggests a specific mechanism regulating the subcellular localization of
      the protein.

PMID- 9632138
TI  - Identification of the critical region of 12p over-representation in testicular
      germ cell tumors of adolescents and adults.
AB  - Cytogenetically, testicular germ cell tumors of adolescents and adults (TGCTs)
      are characterized by gain of 12p-sequences, most often through isochromosome
      formation (i(12p)). Fluorescence in situ hybridization (FISH) has shown that
      i(12p))-negative TGCTs also cryptically contain extra 12p-sequences. The
      consistency of 12p-over-representation in all histological subtypes of TGCTs,
      including their preinvasive stage, suggests that gain of one or more genes on 12p
      is crucial in the development of this cancer. So far, studies aimed at the
      identification of the relevant gene(s) were based on the 'candidate-gene
      approach'. No convincing evidence in favor of or against a particular gene has
      been reported. We combined conventional karyotyping, comparative genomic
      hybridization, and FISH to identify TGCTs with amplifications of restricted
      regions of 12p. Out of 49 primary TGCTs (23 without i(12p), 13 with and 13
      unknown), eight tumors (six without i(12p) and two unknown) showed amplifications
      corresponding to 12p11.1-p12.1. Using bicolour-FISH, physical mapping, and semi
      quantitative polymerase chain reactions, the size of the shortest region of
      overlap of amplification (SROA) was estimated to be between 1750-3000 kb. In
      addition, we mapped a number of genes in and around this region. While fourteen
      known genes could be excluded as candidates based on their location outside this
      region, we demonstrate that KRAS2, JAW1 and SOX5 genes are localized within the
      SROA. While KRAS2 and JAW1 map to the proximal border of the SROA, SOX5 maps
      centrally in the SROA. KRAS2 and JAW1 are expressed in all TGCTs, whereas one 12p
      amplicon-positive TGCT lacks expression of SOX5. The critical region of 12p over
      represented in TGCTs is less than 8% of the total length of the short arm of
      chromosome 12. It will be helpful in the identification of the gene(s) involved
      in TGCT-development.

PMID- 9632139
TI  - Lack of transcriptional repression by max homodimers.
AB  - Max, a basic-helix-loop-helix-leucine zipper (bHLH-ZIP) protein, plays a central
      role in the transcriptional regulation of myc oncoprotein-responsive genes. Myc
      max heterodimers bind to consensus E-box motifs near or within the promoters of
      these genes and activate gene expression, whereas heterodimers between max and
      members of the mad family of bHLH-ZIP proteins promote transcriptional
      repression. In contrast to all other members of the myc network, max readily
      homodimerizes and binds to identical E-box sites in vitro. However, the role for
      max homodimers in transcriptional repression in vivo is unclear. Upstream
      stimulatory factor (USF) is a bHLH-ZIP protein which does not interact with
      members of the myc-max-mad family. By replacing the HLH-ZIP domain of max with
      that from USF, we created a chimeric protein, max(USF), which was
      indistinguishable from max with respect to its ability to homodimerize and bind
      DNA. As expected, however, max(USF) was unable to heterodimerize with any of the
      tested max partner proteins and was incapable of suppressing c-myc target genes.
      Thus, transcriptional repression is an exclusive property of max-mad heterodimers
      and cannot be achieved by max homodimers alone.

PMID- 9632140
TI  - Targeting of the protein chaperone, HSP90, by the transformation suppressing
      agent, radicicol.
AB  - Radicicol, a macrocyclic anti-fungal antibiotic, has the ability to suppress
      transformation by diverse oncogenes such as Src, Ras and Mos. Despite this useful
      property, the mechanism by which radicicol exerts its anti-transformation effects
      is currently unknown. To understand the transformation-suppressing effects of
      radicicol, a biotinylated derivative of radicicol was chemically synthesized and
      used as a probe in a Western-blot format to visualize cellular proteins that
      interact with radicicol. In transformed and untransformed mouse fibroblasts, the
      most prominent cellular protein that bound to radicicol had a molecular weight of
      approximately 90 kDa. Further analysis revealed that this protein was the mouse
      homologue of the 90 kDa heat shock protein (HSP90). This was confirmed by
      demonstrating the ability of radicicol to specifically bind purified human HSP90.
      Specificity of binding was demonstrated by the inhibition of binding of
      biotinylated radicicol by the native drug. Taken together with other studies the
      present observations suggest that the anti-transformation effects of radicicol
      may be mediated, at least in part, by the association of radicicol with HSP90 and
      the consequent dissociation of the Raf/HSP90 complex leading to the attenuation
      of the Ras/MAP kinase signal transduction pathway.

PMID- 9632141
TI  - FGF signaling activates STAT1 and p21 and inhibits the estrogen response and
      proliferation of MCF-7 cells.
AB  - Normal breast tissue as well as most breast tumors are dependent on estrogen for
      growth. Breast tumors often progress to a hormone-independent state which is
      associated with poor prognosis. It has been proposed that activation of growth
      factor signaling pathways in the tumor cells may free them from hormonal control.
      Certain growth factors can mimic estrogen responses by activating the estrogen
      receptor via its phosphorylation by mitogen-activated protein (MAP) kinase. In
      this report, however, we show that fibroblast growth factor (FGF), despite
      activating MAP kinase, is growth-inhibitory for estrogen-dependent MCF-7 breast
      cancer cells. MCF-7 cells treated with FGFs exhibit slower growth than controls
      in both the presence and absence of estrogen, with a concomitant increase in the
      number of cells in G0/G1. Expression of a constitutively activated FGF receptor
      in these cells further decreases their growth rate, which is no longer influenced
      by FGF treatment. Activation of the FGF signaling pathway also reduces the
      induction of an estrogen-responsive CAT reporter plasmid by estrogen, an effect
      which appears to be independent of serine 118 in the estrogen receptor, a MAP
      kinase target site. The inhibitory effects of FGF are probably mediated through
      the sustained induction of the cyclin kinase inhibitor p21/WAF1/CIP1, which is
      upregulated at the mRNA and protein level by FGF. FGF treatment also results in
      the phosphorylation of STAT1. This upregulation of p21 and phosphorylation of
      STAT1 is not detectable in T47D breast cancer cells upon which FGF has no
      inhibitory effect.

PMID- 9632142
TI  - Complex formation between EphB2 and Src requires phosphorylation of tyrosine 611
      in the EphB2 juxtamembrane region.
AB  - The cellular components of the neuronal signaling pathways of Eph receptor
      tyrosine kinases are only beginning to be elucidated. Here we show that in vivo
      tyrosine phosphorylation sites of the Eph receptors EphA3, EphA4, and EphB2 in
      embryonic retina serve as binding sites for the Src-homology 2 (SH2) domain of
      Src kinase. Furthermore, tyrosine-phosphorylated EphB2 was detected in Src
      immunoprecipitates from transfected Cos cells, indicating that EphB2 and Src can
      physically associate. Interestingly, a form of Src with reduced electrophoretic
      mobility and increased tyrosine phosphorylation was detected in Cos cells
      expressing tyrosine-phosphorylated EphB2, suggesting a functional interaction
      between EphB2 and Src. Yeast two-hybrid analysis in conjunction with site
      directed mutagenesis demonstrated that phosphorylated tyrosine 611 in the
      juxtamembrane region of EphB2 is crucial for the interaction with the SH2 domain
      of Src. In contrast, binding of the carboxy-terminal SH2 domain of phospholipase
      Cgamma was not abolished upon mutation of tyrosine 611 in EphB2. Phosphopeptide
      mapping of autophosphorylated full-length EphB2, and wild-type and tyrosine to
      phenylalanine mutants of the EphB2 cytoplasmic domain fused to LexA, showed
      tyrosine 611 in the sequence motif YEDP as a major site of autophosphorylation in
      EphB2. Our mutational analysis also indicated that tyrosines 605 and 611 are
      important for EphB2 kinase activity. We propose Src kinase as a downstream
      effector that mediates the neuron's response to Eph receptor activation.

PMID- 9632143
TI  - Raf-1 independent stimulation of mitogen-activated protein kinase by leukemia
      inhibitory factor in 3T3-L1 cells.
AB  - We show here that treatment of 3T3-L1 cells with leukemia inhibitory factor (LIF)
      stimulated Raf-1 activity in a time- and dose-dependent manner. Although phorbol
      ester failed to activate Raf-1 directly, a protein kinase C-stimulated signal was
      found to be necessary, but not sufficient, for LIF-mediated activation of Raf-1.
      Elevation of intracellular cAMP levels completely blocked Raf-1 activation by
      LIF, but was without effect on the magnitude of mitogen-activated protein kinase
      (MAPK) stimulation by the cytokine, suggesting the presence of a Raf-1
      independent, cAMP-insensitive MAPK kinase kinase (MAPKKK) pathway in 3T3-L1
      cells. Mono Q-fractionation of LIF-stimulated 3T3-L1 extracts identified a single
      peak of MAPKKK activity that was largely insensitive to elevated intracellular
      levels of cAMP, and that failed to correlate with stimulation of either Raf-1 or
      MEKK1 protein kinases. Our results demonstrate that LIF-mediated activation of
      the MAP kinase cascade in 3T3-L1 cells proceeds through both Raf-1-dependent and 
      independent pathways which differ in their sensitivity to inhibition by
      intracellular cAMP.

PMID- 9632144
TI  - Prolonged cell survival enhances peritoneal dissemination of gastric cancer
      cells.
AB  - Bcl-2 and a Bcl-2-binding protein BAG-1 function in protection from apoptosis
      induced by a variety of stimuli. Deregulated expression of Bcl-2 leads to
      inhibition of apoptosis and is correlated with development of various cancers.
      Here, we provide evidence that prolonged cell survival introduced by
      overproduction of Bcl-2 or BAG-1 strongly enhances peritoneal dissemination of
      human gastric cancer MKN74 cells. Gene transfer-mediated overexpression of Bcl-2
      or BAG-1 led to prolonged cell survival of MKN74 cells against serum-starved
      apoptosis and anoikis. When the viable transfectants were inoculated into the
      intraperitoneal cavity of BALB/c nude mice, the Bcl-2-expressing MKN74 cells and
      the BAG-1-expressing MKN74 cells exhibited strongly enhanced peritoneal
      dissemination in BALB/c nude mice and whole disseminated tumor weights were
      increased by 4-fold and 3.3-fold, respectively, compared with the control
      transfectants. The enhanced peritoneal dissemination of MKN74-Bcl-2 and MKN74-BAG
      1 transfectants correlated well with resistance to cell death induced by serum
      starvation and anoikis. However, the overexpression of Bcl-2 or BAG-1 caused no
      significant difference among the transfectants in cell growth rates, either in
      vitro or in vivo. Taken together, these studies demonstrate that resistance to
      apoptosis is a crucial factor for development of peritoneal dissemination of
      human gastric cancer cells.

PMID- 9632145
TI  - ANA, a novel member of Tob/BTG1 family, is expressed in the ventricular zone of
      the developing central nervous system.
AB  - Using a polymerase chain reaction-mediated cloning procedure, we have identified
      a novel member, termed ANA (from Abundant in Neuroepithelium Area), of Tob/BTG1
      family of antiproliferative genes. Molecular cloning and analysis of cDNAs
      revealed that the human and mouse ANA encoded a protein of 252 amino acids. The
      amino-terminal half of ANA was homologous to the previously characterized
      antiproliferative gene products, BTG1, PC3/TIS21/BTG2, and Tob. The human ANA
      gene was localized at chromosome 21q11.2-q21.1. ANA was expressed in a variety of
      tissues and cell lines, its expression being high in the ovary, testis, prostate,
      thymus, and lung. Further analysis revealed that ANA expression was high in the
      ventricular zone of the developing central nervous system. Finally,
      overexpression of ANA impaired serum-induced cell cycle progression from the
      G0/G1 to S phase. In conclusion, ANA is a fourth member of the Tob/BTG1 family
      that might play roles in neurogenesis in the central nervous system.

PMID- 9632146
TI  - Use of an intuitive telemanipulator system for remote trauma surgery: an
      experimental study.
AB  - BACKGROUND: Death from battlefield trauma occurs rapidly. Potentially salvageable
      casualties generally exsanguinate from truncal hemorrhage before operative
      intervention is possible. An intuitive telemanipulator system that would allow
      distant surgeons to remotely treat injured patients could improve the outcome
      from severe injuries. STUDY DESIGN: We evaluated a prototype, four-degree-of
      freedom, telesurgery system that provides a surgeon with a stereoscopic video
      display of a remote operative field. Using dexterous robotic manipulators,
      surgical instruments at the remote site can be precisely controlled, enabling
      operative procedures to be performed remotely. Surgeons (n = 3) used the
      telesurgery system to perform organ excision, hemorrhage control, suturing, and
      knot tying on anesthetized swine. The ability to complete tasks, times required,
      technical quality, and subjective impressions were recorded. RESULTS: Surgeons
      using the telesurgery system were able to close gastrotomies remotely, although
      times required were 2.7 times as long as those performed by conventional
      techniques (451 +/- 83 versus 1,235 +/- 165 seconds, p < 0.002).
      Cholecystectomies, hemorrhage control from liver lacerations, and enterotomy
      closures were successfully completed in all attempts. Force feedback and
      stereoscopic video display were important for achieving intuitive performance
      with the telesurgery system, although tasks were completed adequately in the
      absence of these sensory cues. CONCLUSIONS: We demonstrated the feasibility of
      performing standard surgical procedures remotely, with the operating surgeon
      linked to the distant field only by electronic cabling. Complex manipulations
      were possible, although the times required were much longer. The capabilities of
      the system used would not support resuscitative surgery. Telesurgery is unlikely
      to play a role in early trauma management, but may be a unique research tool for
      acquiring basic knowledge of operative surgery.

PMID- 9632147
TI  - Inflammatory breast carcinoma: a community hospital experience.
AB  - BACKGROUND: Inflammatory breast cancer (IBC) is a rare form of rapidly
      progressive breast cancer. We reviewed the diagnosis, treatment, and outcome of
      IBC in our inner city community-based hospital and compared results with previous
      published reports. STUDY DESIGN: Twenty-five patients were diagnosed and treated
      for IBC at the Catholic Medical Center of Brooklyn and Queens during the 6-year
      period of January 1989 through December 1995. Criteria for inclusion in this
      study were clinical or histopathologic evidence, or both, of inflammatory
      carcinoma. RESULTS: IBC comprised 2.0% (25 of 1,257) of all breast cancer
      patients initially diagnosed during this study. All presented with clinical signs
      of IBC. Invasion of dermal lymphatics by neoplastic cells was demonstrated in 68%
      (17 of 25) of biopsy specimens. Sixty-eight percent (17 of 25) of patients
      presented with metastatic (ie, stage IV) disease and 28% (7 of 25) with stage
      IIIb; one patient (4%) died before staging. Estrogen and progesterone receptor
      studies were done on 72% (18 of 25) of all specimens. Of those patients who died,
      85% were estrogen and progesterone receptor negative; of those surviving, 60%
      were estrogen receptor positive. Twenty (80%) of the 25 patients died, after a
      mean survival of 11.8 months and 5 (20%) remain alive, with a mean survival of
      44.8 months. Of those who died, 85% were stage IV at presentation. All five
      survivors were stage IIIb at presentation. Patients underwent a variety of
      multimodal therapies. Survival was significantly associated with earlier stage at
      diagnosis and estrogen receptor positivity. CONCLUSIONS: IBC is characterized by
      rapid progression and dismal outcome. Earlier stage at diagnosis and positive
      estrogen receptor status suggest a more favorable prognosis. Neoadjuvant
      chemotherapy, as part of a multimodal approach, has significantly improved the
      outcome for IBC, but this is limited to patients with stage IIIb disease. Most of
      our patients presented with stage IV disease. If improvement is to be realized at
      the community level, limited health care resources must be directed toward
      aggressive physician and public education.

PMID- 9632148
TI  - Monitoring hospital trauma mortality using statistical process control methods.
AB  - BACKGROUND: We sought to develop a simple and effective way to monitor trends in
      trauma mortality, using objective clinical categories and methods of statistical
      process control. STUDY DESIGN: Control charts and Pareto analysis were applied to
      trauma mortality data at the Maine Medical Center. We collected data
      prospectively on patients who died in our hospital after acute injury during 1985
      1996 (and retrospectively for 1975-1984) to identify cases requiring medical
      quality review. We excluded from this study patients older than 80 years, those
      whose Glasgow Coma Scale motor component was never > 3 at any time after
      admission, and those with pathologic fractures, carcinomatosis, high
      quadriplegia, or severe burns. The remaining deaths were classified as resulting
      from inability to resuscitate (mostly hemorrhage), neurologic deterioration, or
      organ failure. The annual numbers in each of these categories were evaluated
      under the hypothesis of stationary Poisson processes with mean values equal to
      those seen from 1975-1984. RESULTS: After the exclusions, annual mortality from
      trauma has remained within control limits consistent with the Poisson model.
      Death from neurologic deterioration has shown a trend consistent with significant
      improvement in the process mean. Transient peaks in the other categories did not
      exceed control limits, but Pareto analysis prompted detailed studies of aortic
      and liver trauma. CONCLUSIONS: Process control methodology is easy to apply and
      potentially useful in monitoring hospital trauma mortality.

PMID- 9632149
TI  - Thoracoscopy in the management of posttraumatic persistent pneumothorax.
AB  - BACKGROUND: Persistent posttraumatic pneumothorax (PPP) is an uncommon
      complication of traumatic injuries of the chest, usually managed with suction
      drainage and involving prolonged hospital stays. This study was conducted to
      assess the advantages of using video-assisted thoracoscopic surgery (VATS) in the
      management of patients with PPP. STUDY DESIGN: Eleven patients with PPP underwent
      VATS for diagnosis and for definitive treatment. RESULTS: Before VATS was done,
      all patients had undergone multiple attempts to resolve the PPP; the hospital
      stay before VATS was 10 days (range, 4-14 days). In 10 patients, the cause of the
      PPP was identified and a segmental stapled resection was performed, with complete
      success in resolving the air leak and obtaining pleural synthesis. In another
      patient, the source of the air leak was not identified and a thoracoscopically
      assisted chemical pleurodesis was performed, with immediate cessation of the air
      leak. All chest tubes were removed within 48 hours of the procedure; 9 patients
      were discharged within 72 hours of VATS. Preoperative computed tomography of the
      chest was useful in 2 patients, but bronchoscopy did not disclose any major
      airway injury. CONCLUSIONS: Videothoracoscopy is an accurate, safe, and reliable
      alternative to an open thoracotomy in the management of patients with PPP. In the
      patients in whom the procedure was completed, excellent results were obtained and
      the hospital stay was reduced. We believe that VATS should be used earlier and
      more frequently after failure of conservative management in such patients.

PMID- 9632150
TI  - Ureteral trauma: preoperative studies neither predict injury nor prevent missed
      injuries.
AB  - BACKGROUND: Ureteral injuries are uncommon, and the necessity, accuracy, and
      optimal use of perioperative testing remains unknown. Delays in diagnosis have
      also been associated with significant morbidity, including loss of renal
      function. STUDY DESIGN: The records of all patients (n = 20) admitted with
      ureteral injuries to two Level I trauma centers during a 5-year period were
      reviewed. Data collected included patient demographics, mechanism of injury,
      degree of associated injuries, and presence of gross or microscopic hematuria.
      The use of any pre- or intraoperative testing was specifically noted. The
      location of the ureteral injury was obtained from the operative notes. The
      morbidity and mortality associated with ureteral injuries in the primarily
      diagnosed and the delayed groups were assessed. Presenting signs and symptoms,
      diagnostic testing, and the urologic management of the patients in the delayed
      group were reviewed. RESULTS: All patients were men whose ages ranged from 15 to
      72 years, with a mean age of 29. The mechanisms of injury were gunshot wounds in
      15, stab wounds in 4, and blunt vehicular trauma in 1. Excluding other urologic
      injuries, the incidence of hematuria related to the ureteral injury alone was
      53%. A total of 10 pre- and intraoperative studies were performed, only 2
      demonstrated the ureteral injury. Seventeen patients had their injuries diagnosed
      primarily. In this group, the ureter was repaired by suturing and stenting in 12,
      suturing without a stent in 1 and ureterocystostomy in 4. Delayed diagnosis of
      their ureteral injuries occurred in three patients. All three missed injuries
      occurred in the upper portion of the left ureter. All ureters were successfully
      repaired. There were no mortalities in this group, nor did any patient require a
      nephrectomy. CONCLUSIONS: Direct visualization of the injury is the best and most
      accurate diagnostic modality in ureteral trauma. These results reinforce that a
      thorough exploration of all retroperitoneal hematomas after penetrating trauma
      remain an integral part of the total abdominal exploration for trauma.

PMID- 9632151
TI  - Treatment of vesicovaginal fistula by bladder mucosa autograft technique.
AB  - OBJECTIVES: We evaluated the efficacy of the bladder mucosa autograft technique
      in the treatment of vesicovaginal fistula. STUDY DESIGN: During 15 years, 80
      women with vesicovaginal fistula after gynecologic surgery for benign disease
      were treated by interposition of a bladder mucosa autograft in the fistulous
      tract within 1-3 months of its genesis. RESULTS: The success rate of this
      surgical intervention was 96.3%. There was no late failure. CONCLUSIONS: Bladder
      mucosa autograft interposition seems to be an excellent therapy for closing
      vesicovaginal fistulas. It appears to be more physiologic and easier to perform
      when compared with other transabdominal techniques. Early intervention proved to
      be efficacious and to improve the woman's quality of life.

PMID- 9632152
TI  - Panniculectomy and supraumbilical vertical midline incisions in morbidly obese
      gynecologic oncology patients.
AB  - BACKGROUND: We reviewed the outcomes of panniculectomy and supraumbilical
      vertical midline incisions in morbidly obese women undergoing gynecologic
      operations. STUDY DESIGN: Medical records were reviewed for 62 morbidly obese
      women with a large dependent pannus who underwent gynecologic operations on the
      Gynecologic Oncology Service at the State University of New York at Stony Brook
      between May 1990 and July 1997. Thirty-five patients underwent panniculectomy and
      27 had a supraumbilical vertical midline incision, forming the study groups. The
      patient charts were abstracted for demographic, perioperative, and postoperative
      data. RESULTS: For the entire study population, the average age was 56 years, the
      mean body mass was 128.6 kg, and the mean Quetelet Index was 48.3 kg/m2. The mean
      operative time and estimated blood loss were similar for both groups. Eight
      percent of the patients had urologic injuries, evenly distributed between the
      groups. Postoperative infections, wound breakdowns, and hospital stay were
      greater for the panniculectomy group than for the supraumbilical vertical midline
      incision group (p < 0.05). Uniform use of subcutaneous closed-suction drains
      (since 1995) was associated with a significant reduction in the incidence of
      wound breakdowns and a shorter hospital stay in the panniculectomy group.
      CONCLUSIONS: Panniculectomy and supraumbilical vertical midline incision provide
      reasonable peritoneal access with acceptable rates of postoperative complications
      for morbidly obese women undergoing gynecologic operations.

PMID- 9632153
TI  - Risk factors for early infection of central venous catheters in pediatric
      patients.
AB  - BACKGROUND: In an effort to avoid infections that can lead to the premature
      removal of indwelling central venous catheters (CVCs), the surgical technique and
      host factors present in pediatric recipients of permanent CVCs were reviewed.
      STUDY DESIGN: All patients receiving CVCs over a 17-month period were identified.
      Those patients with fever and positive blood cultures drawn through the CVC
      within 45 days of line placement were labeled as having early infection. A case
      control design was used to select two control patients for each infected patient.
      Charts from both the infection and control groups were reviewed for several
      factors present at the time of CVC placement, including fever, neutropenia
      (absolute neutrophil count [ANC] < 500 and ANC < 1,000), use of perioperative
      antibiotics, diagnosis, CVC site, and type of CVC. Chi-square test with Yates
      correction was used to compare the groups. Odds ratios (ORs) and 95% confidence
      intervals were derived. RESULTS: Among the 473 CVCs placed, early infections
      developed in 53 patients (12%). The control group consisted of 106 patients.
      Neutropenia was present in 16 of 53 infected patients versus 8 of 106 controls (p
      = 0.004, OR = 5.30). Perioperative antibiotics were given to 25 of 53 infected
      patients versus 72 of 106 controls (p = 0.02, OR = 0.42). Fever was present in 12
      of 53 infected patients versus 14 of 106 controls (p = 0.19, OR = 1.92). Factors
      that were equally prevalent between the groups and that did not appear to
      influence the CVC infection rate included a diagnosis of malignancy, CVC type,
      and site of placement. Of the 53 infected catheters, 16 (30%) could not be
      cleared of infection and were removed. CONCLUSIONS: This study documents that
      neutropenia and failure to administer prophylactic antibiotics are risk factors
      for the development of early CVC infection in pediatric patients. To avoid early
      infection and possible premature CVC removal, we recommend that placement of
      permanent CVCs be postponed until the ANC is > 1,000. Perioperative antibiotics
      should be given. A trend toward higher infection rates was seen in patients with
      preoperative fever.

PMID- 9632154
TI  - Density of Helicobacter pylori infection in patients with peptic ulcer
      perforation.
AB  - BACKGROUND: A lack of change in prevalence of severe ulcer complications
      requiring emergency operation has been reported, despite the common use of
      histamine-2 (H2)-receptor antagonists and proton pump inhibitors. This may be
      attributable to use of ulcerogenic drugs or Helicobacter pylori (HP) infection,
      or both. In this study, HP infection was evaluated semiquantitatively in patients
      with peptic ulcer who required surgery, and the severity of histologic change was
      investigated. METHODS: We reviewed a total of 113 consecutive patients (98 men
      and 15 women) operated on for perforation, hemorrhage, or stenosis of
      gastroduodenal ulcer between January 1986 and December 1995. Detection of HP was
      carried out by immunohistochemical staining. We graded the density of HP
      infection according to the number of individual HP bacteria counted in a highly
      magnified visual field (x 1,000 of light microscopy). The grade of HP infection
      was defined as follows: (0) = 0; (1+) = 1-9; (2+) = 10-29; (3+) = 30-99; (4+) >
      or = 100. The severity of gastritis was evaluated by histologic examination using
      the criteria of Rauws. RESULTS: Although the number of operations for
      gastroduodenal ulcer declined significantly, the rate of emergency operation for
      gastroduodenal ulcer increased from 60% to 90%, with the result that the
      frequency of operations for perforation or bleeding remained virtually constant
      and that for stenosis significantly decreased. HP infection was more prevalent in
      perforated ulcer (92%) than hemorrhagic ulcer (55%) or stenotic ulcer (45%). The
      grades of HP infection were 3.0 +/- 0.14 (mean +/- SEM) in perforated ulcer, 2.3
      +/- 0.34 in hemorrhagic ulcer, and 2.5 +/- 0.22 in stenotic ulcer. Perforated
      ulcer was associated with significantly more severe HP infection and gastritis
      changes than hemorrhagic ulcer or stenotic ulcer. CONCLUSIONS: This study
      indicates that patients with perforated ulcer were infected with HP more severely
      than those with hemorrhagic ulcer or stenotic ulcer at the time of surgery. A
      close relationship was observed between the perforated ulcer and the density of
      HP infection determined semiquantitatively using immunohistochemical stain.

PMID- 9632155
TI  - Small-bowel tumors.
AB  - BACKGROUND: The rarity, delayed presentation, and diagnostic difficulty of small
      bowel tumors prompted this study. STUDY DESIGN: Charts were reviewed
      retrospectively for 85 patients with 89 small-bowel tumors (22 primary malignant,
      23 primary benign, and 44 metastatic) over a 10-year period (1986-1996) at
      Louisiana State University Medical Center-Shreveport and two affiliated hospitals
      in Shreveport. RESULTS: Of the primary malignant tumors, 10 carcinoids and 11
      duodenal adenocarcinomas were identified. Most primary benign tumors were
      adenomatous or hyperplastic polyps, diagnosed by esophagogastroduodenoscopy.
      Metastatic tumors accounted for nearly 50% of all small-bowel tumors. Across all
      three tumor types, the most common presenting signs and symptoms were abdominal
      pain and nausea and vomiting. In addition, patients with benign tumors were more
      commonly presented with gastrointestinal hemorrhage, and those with metastatic
      tumors were more likely to present with obstruction. The mean interval from the
      onset of signs and symptoms to operation was 54 days for primary malignant tumors
      and 330 days for primary benign tumors. Esophagogastroduodenoscopy and computed
      tomography of the abdomen were occasionally helpful in diagnosis. Among the 22
      primary malignant tumors, curative resections were performed in 11 patients (for
      9 carcinoids and 2 adenocarcinomas) and palliative resections were performed in
      10 patients (for 9 adenocarcinomas and 1 myxoliposarcoma). One patient had
      carcinomatosis from colon cancer and an incidentally discovered ileal carcinoid;
      this carcinoid was not included in this group of resections for primary malignant
      small-bowel tumors. All operations for 39 (of 44) patients with metastatic tumors
      were palliative. The remaining 5 (of 44) patients had metastatic duodenal cancer
      (confirmed by esophagogastroduodenoscopy or endoscopic retrograde
      cholangiopancreatography with biopsy) and did not undergo laparotomy. Surgical
      complications occurred more commonly with metastatic than with primary malignant
      tumors. Patients with primary malignant tumors had a 5-year survival rate of 36%.
      CONCLUSIONS: These findings demonstrate that small-bowel tumors are difficult to
      diagnose because of delayed presentation, nonspecific signs and symptoms, and
      lack of accurate diagnostic studies. If the overall survival of patients with
      small-bowel tumors is to be improved, clinicians must have a high index of
      suspicion and be willing to perform exploratory celiotomy early.

PMID- 9632156
TI  - The Malone antegrade continence enema procedure in the management of patients
      with spina bifida.
AB  - BACKGROUND: In patients with spina bifida, traditional bowel management programs
      such as suppositories, retrograde enemas, and manual disimpaction have been
      largely unsatisfactory. The Malone antegrade continence enema (ACE) procedure has
      largely changed our approach to bowel management in this patient group. STUDY
      DESIGN: Over a 3-year period between January 1994 and January 1997, 27 patients
      with spina bifida underwent the Malone ACE procedure at our institutions. At the
      time of their ACE procedure, four patients underwent simultaneous continent
      urinary diversion and three had simultaneous small-bowel bladder augmentation.
      All the patients were evaluated for 9 months or more after their procedure, and
      10 of the patients have been followed for more than 2 years. RESULTS:
      Postoperatively, predictable bowel control and continence were achieved in 19 of
      the 27 patients, but 6 had some rectal soiling requiring a sanitary pad. All
      patients were out of diapers and none reported stomal leakage. Eighteen of the 27
      patients were able to manage independently and 9 required assistance. Two
      patients had stopped using their ACE stoma despite good technical results. The
      appendix was used as a catheterizable stoma in 15 of the 27 patients. The
      appendix was not available in 12 patients, so a tubularized cecal flap was used
      in 9 and a small-bowel neoappendix was created in 3. Complications included
      stomal stenosis in 5 patients, cecal-flap necrosis in 1, and stomal granulations
      in 3. CONCLUSIONS: We believe that the ACE procedure provides reliable colonic
      emptying and avoids fecal soiling in the majority of individuals, and we find it
      widely and enthusiastically accepted by patients with spina bifida.

PMID- 9632157
TI  - The role of diagnostic laparoscopy in pancreatic and periampullary malignancies.
AB  - BACKGROUND: The role of diagnostic laparoscopy before laparotomy in patients with
      pancreatic or periampullary malignancies remains controversial. We analyzed the
      value of using diagnostic laparoscopy to avoid laparotomy in these patients.
      STUDY DESIGN: Between November 1993 and December 1996, 254 patients with
      pancreatic or periampullary malignancies were treated. In 74 patients, multiple
      distant metastases precluded further surgical treatment. In all, 180 patients
      underwent laparotomy for pancreatic cancer (119 patients) or periampullary cancer
      (61 patients). Preoperatively, all patients underwent computed tomography for
      staging and to assess resectability of the tumor. Based on the results of the
      imaging procedure, the patients were scheduled for either tumor resection or a
      palliative operation. RESULTS: Twenty-one of 180 patients (12%) with pancreatic
      or periampullary malignancies were scheduled preoperatively for nonresectional
      operations because of distant metastasis or retroperitoneal tumor infiltration.
      In none of these patients was the operative strategy changed. In 159 of 180
      patients (88%), a pancreatic resection was planned preoperatively; 119 patients
      underwent pancreatic resection. In the remaining 40 patients preoperatively
      scheduled for tumor resection, removal of the tumor was not possible. In 24, this
      resulted from tumor infiltration into the retropancreatic vessels, and in 16 it
      resulted from liver or peritoneal metastasis detected for the first time
      intraoperatively. These 16 patients (10%) could have benefited from diagnostic
      laparoscopy. Similar results were found in the subgroup of 119 patients with
      pancreatic cancer, of whom 102 were planned for tumor resection and 17 for
      palliative operation. Of the 102 patients planned preoperatively for tumor
      resection, 71 patients (70%) underwent pancreatic resection. In the remaining 31
      patients scheduled for tumor resection, removal of the tumor was not possible: in
      17 because of tumor infiltration into the retropancreatic vessels and in 14
      because of liver or peritoneal metastasis detected for the first time
      intraoperatively. These 14 patients (14%) also would have benefited from
      laparoscopy. CONCLUSIONS: Preoperative computed tomography is a reliable
      technique to detect tumor metastasis in patients with pancreatic or periampullary
      cancer. Unlike other investigators, we found that only 10% of patients with
      periampullary or pancreatic cancer and 14% of patients with pancreatic cancer
      might profit from laparoscopy. Because of this low number, laparoscopy cannot
      generally be recommended for patients with pancreatic or periampullary cancer
      before laparotomy.

PMID- 9632158
TI  - Venovenous bypass in adult orthotopic liver transplantation: routine or selective
      use?
AB  - BACKGROUND: The role of venovenous bypass (VVB) during orthotopic liver
      transplantation (OLT) remains controversial. The aims of this study were to
      evaluate the current role of VVB at all major centers in North America, to
      examine the results of OLT and complications of VVB between two periods with a
      strict policy for routine versus selective use of VVB, and to review the
      literature. STUDY DESIGN: A survey of 50 major liver transplant centers was
      conducted using mailed questionnaires. A retrospective chart review was performed
      for 547 OLT patients having transplantation during two distinct periods with a
      strict policy for routine versus selective use of VVB at the University of
      Toronto, Canada, and at Duke University Medical Center, Durham, North Carolina.
      The literature was reviewed with a focus on the benefits and indications for
      routine versus selective use of VVB. RESULTS: Thirty-eight (76%) of 50 centers
      responded. Sixteen (42%) of them used VVB routinely, with a reported complication
      rate of 10-30%. Lymphocele and hematoma were the most common complications, but
      patients having major vascular injury, air embolism, and death were reported. A
      recent change to selective use of VVB was reported in 30% of the centers (11 of
      38). In the Duke-Toronto series, the complication rates were similar between the
      two periods, at 13.4% and 18.8%, respectively. The outcome of OLT was not
      influenced by the policy of routine or selective use of VVB. CONCLUSIONS: There
      is a trend away from the routine use of VVB during OLT. Intraoperative
      hemodynamic instability during the hepatectomy and a failed trial of hepatic
      venous occlusion were the most important criteria for using VVB. We conclude that
      VVB should be used selectively to avoid associated complications and to decrease
      operative time and costs.

PMID- 9632159
TI  - Transitioning to the future.

PMID- 9632160
TI  - Rhabdomyolysis and myoglobinuric renal failure in trauma and surgical patients: a
      review.

PMID- 9632161
TI  - Resection of tumors of the pararenal inferior vena cava with in situ perfusion of
      the right kidney and graft replacement with bovine pericardium.

PMID- 9632162
TI  - Teebi hypertelorism syndrome with tetralogy of Fallot.
AB  - A 34-month-old boy presented with clinical manifestations of Teebi hypertelorism
      syndrome including prominent forehead with frontal bossing, hypertelorism,
      exophthalmos due to shallow orbits, a short and broad nose with anteverted nares,
      small hands and feet with interdigital webbing, umbilical hernia, and shawl
      scrotum. In addition, he had previously undescribed manifestations including
      tetralogy of Fallot, bilateral inguinal testes, and bifid scrotum. His
      phenotypically normal mother showed splayed labiae majora during her pregnancy, a
      possible manifestation of the syndrome.

PMID- 9632163
TI  - Oculocerebrorenal syndrome of Lowe: three mutations in the OCRL1 gene derived
      from three patients with different phenotypes.
AB  - The oculocerebrorenal syndrome of Lowe (OCRL) is an X-linked multisystem disorder
      with major abnormalities of eyes, nervous system, and kidneys. Clinical
      manifestations include congenital cataract, mental retardation, and renal tubular
      dysfunction. A gene (OCRL1) responsible for OCRL was identified by positional
      cloning and its product OCRL-1 protein was shown to be a phosphatidylinositol 4,5
      bisphosphate [PtdIns(4,5)P2] 5-phosphatase localized to the Golgi apparatus. We
      describe three mutations in OCRL1, one in a patient with severe phenotype and two
      in patients with moderate phenotype (degree of mental retardation and
      musculoskeletal abnormalities). The patient with severe phenotype had a G-to-A
      transition at nucleotide (nt) 1,739, causing an Arg-to-Gln substitution at amino
      acid 577, and one patient with moderate phenotype had a C-to-G transversion at nt
      1,812, leading to a His-to-Gln substitution at amino acid 601. Both Arg-577 and
      His-601 are encoded by exon 15 and are probably important for proper function of
      this protein, since these are conserved in various enzymes catalyzing
      dephosphorylation of inositol compounds. In the other patient with the moderate
      phenotype, there was a G-to-A transition at nt 2,797 located at the 3'-end of
      exon 22. This substitution led to a skip of the same exon as well as conversion
      of codon-930 from GCT (Ala) to ACT (Thr) in the normal-size transcript. When we
      measured the enzyme activity in skin fibroblasts from the three patients, the
      activity was less than 10%, compared to findings in normal controls. Western blot
      analysis showed absence or severe decrease in OCRL-1 protein in cell lysates
      derived from these patients.

PMID- 9632164
TI  - Pseudoachondroplasia with de novo deletion [del(11)(q21q22.2)].
AB  - Pseudoachondroplasia (PSACH) is a relatively common osteochondrodysplasia
      characterized clinically by short-limbed short stature with normal face, and
      radiographically by platyspondyly and dysplasias of epiphyses and metaphyses of
      the tubular bones. Recently, mutation of cartilage oligomeric matrix protein has
      been identified in PSACH. However, clinical variability and genetic heterogeneity
      have been reported in PSACH, indicating a possible existence of a second PSACH
      gene. Here, we report on a patient with a typical severe form of PSACH who had a
      de novo interstitial deletion in the long arm of chromosome 11
      [del(11)(q21q22.2)]. The size of the deletion was estimated at 0.8-7.3 Mb using
      fluorescent in situ hybridization (FISH). This deletion may contain or disrupt a
      second PSACH locus.

PMID- 9632166
TI  - Efficient, robust, and unified method for mapping complex traits (I): two-point
      linkage analysis.
AB  - The completion of a preliminary human genome map and development of molecular
      methods have enabled researchers to assay a large number of polymorphic markers
      that are evenly spaced along the entire human genome. Among many applications,
      marker data are valuable for mapping complex traits through linkage or linkage
      disequilibrium analysis, the former of which is the focus of this paper, the
      first in a series on this subject. Formalizing the concept and computation for
      linkage analysis, Elston and Stewart [1971; Human Heredity 21:523-542] introduced
      a likelihood function to capture relevant genetic information and a recursive
      algorithm for computing the likelihood function. However, the computing burden is
      prohibitive in processing complex pedigrees. Since that fundamental development,
      improving the computational algorithm and extending the method has been a dynamic
      area of research. The primary objective of this communication is to introduce a
      semiparametric method for linkage analysis. It is a particularly suitable
      approach with desirable properties for mapping complex traits that may be binary,
      continuous, and partially observed (i.e., censored). It incorporates candidate
      genes, environmental factors, and their interactions with the putative gene and
      is expected to be robust and efficient in comparison with likelihood-based
      methods. The properties of the estimates have been studied in finite samples with
      a limited simulation study. This method is illustrated with an application to
      family data contributed to the Breast Cancer Consortium.

PMID- 9632165
TI  - Rarity of PIT1 involvement in children from Russia with combined pituitary
      hormone deficiency.
AB  - To ascertain the molecular background of combined pituitary hormone deficiency,
      screening for mutations in the pituitary-specific transcription factor (Pit-1/GHF
      1) gene (PIT1) was performed on a cohort of 15 children from Russia with combined
      growth hormone (GH)/prolactin (Prl)/thyroid-stimulating hormone (TSH) deficiency.
      The group of patients, suspected of PIT1 mutations, consisted of four familial
      cases (seven patients) and eight sporadic cases. All had complete GH deficiency
      and complete or partial Prl and TSH deficiency. Direct sequencing of all six
      exons of PIT1 and its promoter region showed a C to T transition mutation at
      codon 14 of exon 1 in a 3 8/12-year-old girl. This novel PIT1 mutation results in
      a proline to leucine substitution (P14L). The patient was heterozygous for mutant
      and normal alleles. The heterozygous P14L mutation was also present in her mother
      as well as in her maternal aunt and grandmother, all of whom were phenotypically
      normal. There was no mutation in the father's DNA, suggesting the need for
      reevaluation of genomic imprinting. In other children of our series, no mutation
      in PIT1 or in its promotor region was identified. This is the first report on the
      analysis of PIT1 and its promoter region in Russian children with GH/Prl/TSH
      deficiency. However, as the involvement of PIT1 mutation is rare in Russia, the
      other negative cases need to be analyzed for another candidate gene responsible
      for combined GH/Pr/TSH deficiency.

PMID- 9632167
TI  - Facial measurements in clinical genetics: How important are the instruments we
      use?
AB  - Prompted by our finding that a popular compendium of clinical measurements often
      suggests a transparent ruler as a suitable substitute for anthropometric calipers
      (which were typically used by the original researchers to collect the normative
      data), we compared facial measurements taken with a ruler and calipers. Our
      objectives were to compare facial measurement data taken with these instruments
      by two classes of observer: expert and inexperienced. Ten facial measurements
      were repeated on four medically normal women by one expert and one inexperienced
      observer. Both observers' data showed that the caliper-derived means were usually
      the larger, but, whereas the expert observer's caliper-derived data typically
      were the least variable, the novice observer had smaller standard deviations and
      ranges for the ruler-derived data. Statistically significant differences were
      found between the ruler- and caliper-derived data from both observers on all four
      subjects, except for subnasale-pogonion and stomion-pogonion. For the novice
      observer only, endocanthion-endocanthion, left exocanthion-endocanthion, and
      alare-alare were also nonsignificant. The calibrations of the sliding caliper and
      ruler were compared to determine if differences between them could explain the
      statistical results, but were the same. We concluded that the differences between
      the caliper- and ruler-derived measurements resulted because the ruler often
      could not be placed directly on the landmarks, as could the arms of the calipers.
      We recommend that clinicians interested in taking facial measurements to assess
      their patients consult the original publications for information on the
      techniques and instruments used so that reliable comparisons with the normative
      data can be made.

PMID- 9632168
TI  - Constitutional del(19)(q12q13.1) in a three-year-old girl with severe phenotypic
      abnormalities affecting multiple organ systems.
AB  - We present the clinical, cytogenetic, and molecular studies on a constitutional
      deletion of 19q ascertained prenatally due to decreased fetal activity and IUGR.
      Chromosome analysis by GTG banding on amniocytes suggested a del(19)(q13.1q13.3),
      but the analysis of microsatellites by PCR demonstrated that the deletion
      involved the distal segment of q12 and the proximal segment of q13.1 (15 cM). The
      severely affected female infant born at 38 weeks has clinical findings that may
      be related to haploinsufficiency of specific genes within 19q12.1-->q13.1 that
      control important processes of normal development and cell function.

PMID- 9632169
TI  - Yield of mtDNA mutation analysis in 2,000 patients.
AB  - The multiplex polymerase chain reaction-allele specific oligonucleotides
      (PCR/ASO) dot blot hybridization method was used to detect 44 mitochondrial DNA
      point mutations in 2,000 patients suspected as having mitochondrial DNA
      disorders. These point mutations are classified into four categories. Category I
      consists of primary disease-causing, heteroplasmic point mutations. Homoplasmic
      nucleotide substitutions that have been reported to be possibly disease
      associated are in Category II. Homoplasmic nucleotide substitutions that are
      thought to be benign polymorphism are included in category III. The novel
      nucleotide substitutions recently discovered in our laboratory by single strand
      conformation polymorphism analysis are in category IV. Frequencies of these 44
      nucleotide substitutions in 2,000 patients and 262 control individuals were
      studied. The results indicated that analysis of 12 recurrent disease-causing
      point mutations in category I identified 5.4% of the patients suspected as having
      mitochondrial DNA disorders. Since the mitochondrial disorders are a group of
      complex, heterogeneous, and multisystemic diseases, it is often difficult to
      confirm clinical diagnosis without molecular studies. Thus, the multiplex PCR/ASO
      method is an effective approach for initial screening of mtDNA mutations in
      patients suspected as having mitochondrial DNA disorders.

PMID- 9632170
TI  - Random X inactivation in a girl with a balanced t(X;9) and an abnormal phenotype.
AB  - X inactivation is the process by which mammalian females achieve dosage
      compensation by transcriptionally silencing one X chromosome. In chromosomally
      normal females, this process is random. However, most females with one abnormal X
      chromosome demonstrate complete skewing of X inactivation, presumably as the
      result of cell selection. We present a mentally retarded girl with a
      46,X,t(X;9)(q28;q12) karyotype. Analysis of this patient's lymphocytes, using
      late replication banding and methylation assays for the androgen receptor (AR)
      and fragile X mental retardation (FMR1) genes, did not show the predicted
      nonrandom X inactivation pattern. Thus, this patient is functionally disomic for
      Xq28-qter in a proportion of her cells, most likely resulting in her abnormal
      phenotype. This case demonstrates the utility of correlating X inactivation
      patterns with phenotype in females with one structurally abnormal X chromosome,
      and suggests that both cytogenetic and molecular X inactivation studies should be
      included in the routine study of these individuals.

PMID- 9632171
TI  - Cephalometric analysis of families with dominantly inherited Crouzon syndrome: an
      aid to diagnosis in family studies.
AB  - Crouzon syndrome (CS) is an autosomal dominant condition comprising orbital
      proptosis, midfacial hypoplasia, premature sutural synostosis, and altered
      proportions of bone lengths in the hands. In families the CS trait is highly
      variable. Several cases of affected sibs born to unaffected parents have been
      explained by germinal mosaicism. We hypothesized that cephalometric and
      metacarpophalangeal analysis may help to classify affected and unaffected
      subjects within families when clinical diagnosis is difficult. Posterior-anterior
      and lateral cephalometric radiographs and hand films were taken of 10 CS patients
      and 18 unaffected relatives. Sixty-two craniofacial and 19 hand linear and
      angular measurements were made on each subject and standardized by conversion to
      z-scores using published normal standards. Ten craniofacial variables were
      selected for use in a stepwise forward discriminant function analysis to develop
      an equation which could be used to discriminate CS patients from normal subjects.
      A two-group discriminant function using four craniofacial variables and one hand
      variable correctly classified the CS patients and relatives 100% of the time. The
      results suggest that relatively few facial variables are needed to differentiate
      most cases of CS but the addition of one or more hand variables may increase the
      sensitivity. DNA testing is necessary to adequately demonstrate incomplete
      penetrance in CS, but pretesting subjects for molecular studies using these
      methods may improve results.

PMID- 9632172
TI  - Twin zygosity testing for medical purposes.
AB  - After being poisoned by eating the mushroom species Cortinarius speciosissimus, a
      twin developed interstitial nephritis with acute renal failure. He received a
      renal transplant from his living twin brother, who was presumed dizygotic on
      phenotypic grounds. Fifteen years later, the twins were zygosity tested by DNA
      "fingerprint analysis" and found to be monozygotic, despite important phenotypic
      discordances. The recipient has discontinued immunosuppression therapy and
      remains well after 9 months. We suggest that, for medical and other reasons,
      zygosity should be determined at birth on all like-sexed twins.

PMID- 9632173
TI  - Chromosomal localization of the 5-HT1F receptor gene: no evidence for involvement
      in response to sumatriptan in migraine patients.
AB  - The 5-HT1F receptor, which is present in both human vascular and neuronal tissue,
      may mediate the therapeutic effect and/or side-effects of sumatriptan. We
      investigated the chromosomal localization of the 5-HT1F receptor gene and the
      relation between eventually existing polymorphisms and the clinical response to
      sumatriptan in migraine patients. The 5-HT1F receptor gene was localized using a
      monochromosomal mapping panel, followed by a radiation-reduced hybrid mapping and
      fluorescent in situ hybridization. The results of these techniques show that the
      5-HT1F receptor gene is localized at 3p12. We investigated the presence of
      polymorphisms by single strand conformation polymorphism analysis in 14 migraine
      patients who consistently responded well to sumatriptan, 12 patients who
      consistently experienced recurrence of the headache after initial relief, 12
      patients with no response to sumatriptan, and in 13 patients who consistently
      experienced chest symptoms after use of sumatriptan. No polymorphisms were
      detected in any of the patients. We therefore conclude that genetic diversity of
      the 5-HT1F receptor gene is most probably not responsible for the variable
      clinical response to sumatriptan.

PMID- 9632174
TI  - Evidence for complex nuclear inheritance in a pedigree with nonsyndromic deafness
      due to a homoplasmic mitochondrial mutation.
AB  - The relationship between mitochondrial genotype and clinical phenotype is
      complicated in most instances by the heteroplasmic nature of pathogenic
      mitochondrial mutations. We have previously shown that maternally inherited
      hearing loss in a large Arab-Israeli kindred is due to the homoplasmic A1555G
      mutation in the mitochondrial 12S ribosomal RNA gene [Prezant et al., 1993: Nat
      Genet 4:289-294]. Family members with this mutation have phenotypes ranging from
      profound hearing loss to completely normal hearing, and we have shown that there
      is genetic and biochemical evidence for nuclear gene involvement in this family
      [Bu et al., 1993: Genet Epidemiol 9:27-44; Guan et al., 1996: Hum Mol Genet 5:963
      971]. To identify such a nuclear locus, two candidate genes were excluded through
      linkage analysis and sequencing, and a genome-wide linkage search in family
      members who all have the identical homoplasmic mitochondrial mutation, but differ
      in their hearing status, was performed. In two stages a total of 560 polymorphic
      genetic markers was genotyped, and the data were analyzed under model-dependent
      and model-free assumptions. No chromosomal region was identified as a major
      contributor to the phenotypic expression of the mitochondrial mutation. Thus, in
      this simplified paradigm of a homoplasmic mitochondrial mutation in a single
      kindred who all live in the similar environment of a small village, the
      penetrance of the mitochondrial mutation appears to depend on the interaction of
      multiple nuclear genes.

PMID- 9632175
TI  - Autoimmune enteropathy in Schimke immunoosseous dysplasia.
AB  - The clinical phenotype of Schimke immunoosseous dysplasia (SID) is characterized
      by growth retardation, renal failure, recurrent infections, cerebral infarcts,
      and skin pigmentation beginning in childhood. We report here on a 4-year-old male
      child who had all characteristic symptoms of SID, and, in addition, vomiting and
      prolonged diarrhea. The study results suggest that malabsorption, demonstrated as
      increased serum immunoglobulin A anti-gliadin antibody, steatorrhea and partial
      villous atrophy of the jejunal small bowel, is a previously unrecognized feature
      of SID.

PMID- 9632176
TI  - Anomalies in Down syndrome individuals in a large population-based registry.
AB  - In a population of close to 2.5 million infants born from 1983 to 1993 registered
      in the California Birth Defects Monitoring Program, we compared the prevalence of
      structural birth defects among 2,894 infants with Down syndrome (DS) with that of
      infants without DS. Among 61 defects uniformly ascertained in affected and
      unaffected infants, 45 were significantly more common in DS, with
      atrioventricular canal (risk ratio = 1,009), duodenal atresia (risk ratio = 265),
      and annular pancreas (risk ratio = 430) being the most common. Most defects of
      blastogenesis and most midline defects were either nonsignificantly associated or
      not observed in infants with DS. Theories on the pathogenesis of defects in
      trisomies must account for the lack of and for the presence of specific defects.

PMID- 9632177
TI  - Classification of limb defects.

PMID- 9632178
TI  - Transchoroidal approach to the third ventricle: an anatomic study of the
      choroidal fissure and its clinical application.
AB  - OBJECTIVE: We review the anatomic features of the lateral ventricle, the foramen
      of Monro, the third ventricle, and the choroidal fissure, and we describe the
      transchoroidal approach to the third ventricle. This approach consists of opening
      the taenia fornicis of the choroidal fissure in the body of the lateral ventricle
      and approaching the third ventricle between the two internal cerebral veins. This
      route allows further posterior enlargement of the foramen of Monro without
      sacrificing any neural structures. When necessary, the anterior septal vein can
      be sacrificed. METHODS: Twenty adult cadaveric brains and four adult cadaveric
      heads were studied, using a magnification ranging from 3 times to 40 times, after
      perfusion of the arteries and veins with colored latex. RESULTS: The choroidal
      fissure is a natural cleft between the thalamus and the fornix, and it is
      identified by following the choroid plexus in the lateral ventricle. The choroid
      plexus in the body of the lateral ventricle originates from the tela choroidea of
      the roof of the third ventricle and is apparently attached to the fornix by the
      taenia fornicis and to the thalamus by the taenia choroidea. The taenia is
      actually the ependyma that covers the internal wall of the ventricular cavity and
      the choroid plexus. CONCLUSION: An understanding of the choroidal fissure is
      fundamental for use of the transchoroidal approach. Unlike transforaminal,
      subchoroidal, subforniceal, and interforniceal approaches to the third ventricle,
      which sacrifice some neural or vascular structures, the transchoroidal approach
      follows a natural route, and certainly it is one of the options to be considered
      when entry into the third ventricle is required.

PMID- 9632179
TI  - Risks of surgical management for cavernous malformations of the nervous system.
AB  - OBJECTIVE: As more information evolves regarding the natural history of cavernous
      malformations (CMs), the risks of operative intervention must be balanced against
      nonoperative management. In an attempt to better delineate the surgical risks for
      operable CMs, we undertook a retrospective analysis of 94 patients with 97 CMs
      surgically excised at the Massachusetts General Hospital. METHODS: Data regarding
      surgical complications and outcome measures, including neurological status and
      seizure outcome, were analyzed. RESULTS: The incidence of transient neurological
      morbidity was 20.6%, but only 4 of the 97 operations (4.1%) resulted in
      persistent disabling neurological complications and 2 (2.1 %) in nondisabling
      deficits. There was no operative mortality. Brain stem lesions (n=14) were
      associated with the highest incidence of neurological complications, both
      transient and persistent (odds ratio, 4.8; 95% confidence interval, 1.5-15.7).
      The overall neurological outcome was excellent or good in 89.7% of all lesions:
      96.8% of lobar CMs (n=63), 64.2% of brain stem CMs (n=14), 87.5% of cerebellar
      CMs (n=8), 100% of cranial nerve CMs (n=4), and 75% of spinal cord CMs (n=8).
      Patients with brain stem and spinal cord CMs were in poorer preoperative
      neurological condition than were patients with CMs in other locations and
      therefore had a significantly reduced level of function after surgery (P < 0.01).
      There was improvement in 35.7% of the patients with brain stem lesions and 62.5%
      of the patients with spinal cord lesions after surgery. In the 38 patients
      presenting with seizures, 97% were seizure-free after surgery. CONCLUSION: The
      risks of operative management of CMs varies based on location. When evaluating
      patients with operable CMs for surgery, the incidence of complications as well as
      final neurological outcome should be carefully weighed against the existing
      knowledge of the natural history of lesions managed expectantly.

PMID- 9632180
TI  - Stereotactic radiosurgery for cavernous malformations: Kjellberg's experience
      with proton beam therapy in 98 cases at the Harvard Cyclotron.
AB  - OBJECTIVE: The lack of treatment options for surgically inaccessible cavernous
      malformations has made radiosurgery a possible alternative to conservative
      management. The few previous reports of radiosurgical efficacy have been limited
      by small numbers, short follow-up, or lack of attention to the full spectrum of
      end points, including neurological disability. In an attempt to elucidate the
      risk-to-benefit ratio of radiosurgery for cavernous malformations, we undertook a
      retrospective analysis of of 95 patients with 98 lesions treated by the late
      Raymond N. Kjellberg. METHODS: Patients were followed for an average of 5.4 years
      (range, 0.3-12.3 yr), and data regarding hemorrhage, seizure, neurological
      disability, and incidence of radiation-induced complications were gathered.
      RESULTS: The analysis revealed a drop in annual hemorrhage rates from 17.3% per
      lesion per year before treatment to 4.5% per lesion per year after a latency
      period of 2 years. Improvement in seizure control was evident. However, a 16%
      incidence of permanent neurological deficit and a 3% mortality rate were
      attributable to radiographically confirmed radiation-induced complications.
      Neurological disability scores, measured by the modified Rankin disability scale,
      indicated a significant decline in neurological functioning during the follow-up
      interval, a result of the combined effects of radiation-related injury,
      hemorrhage, and clinical progression of the lesion. CONCLUSION: We conclude that
      although radiosurgery does seem to reduce hemorrhage, there is potential for
      complications and continued lesion progression after radiosurgery. These risks
      and benefits must be carefully balanced against the natural history of untreated
      lesions if the use of radiosurgery is considered.

PMID- 9632181
TI  - Factors associated with successful arteriovenous malformation radiosurgery.
AB  - OBJECTIVE: To analyze the clinical and angiographic variables that affect the
      results of arteriovenous malformation (AVM) radiosurgery and to propose a new
      method of reporting patient outcomes after AVM radiosurgery. This method
      incorporates both the obliteration status of the AVMs and the postoperative
      neurological condition of the patient. METHODS: Patient outcomes were defined as
      excellent (nidus obliteration and no new deficits), good (nidus obliteration with
      a new minor deficit), fair (nidus obliteration with a new major deficit),
      unchanged (incomplete nidus obliteration without a new deficit), poor (incomplete
      nidus obliteration with any new deficit), and dead. Two hundred twenty patients
      who underwent AVM radiosurgery at our center before 1992 were subjected to a
      multivariate analysis with patient outcomes as the dependent variable. RESULTS:
      Multivariate analysis determined four factors associated with successful AVM
      radiosurgery: smaller AVM volume (P=0.003), number of draining veins (P=0.001),
      younger patient age (P=0.0003), and hemispheric AVM location (P=0.002).
      Preradiosurgical embolization was a negative predictor of successful AVM
      radiosurgery (P=0.02). CONCLUSION: AVM obliteration without new neurological
      deficits can be achieved in at least 80% of patients with small volume,
      hemispheric AVMs after single-session AVM radiosurgery. Future studies on AVM
      radiosurgery should report patient outcomes in a fashion that incorporates all
      the factors involved in successful AVM radiosurgery.

PMID- 9632182
TI  - Risks and benefits of diagnostic angiography after aneurysm surgery: a
      retrospective analysis of 597 studies.
AB  - INTRODUCTION: Cerebral angiography performed after aneurysm surgery can identify
      causes of morbidity and mortality that may be corrected. The risks and benefits
      of angiography that is performed after aneurysm surgery, however, have not been
      clearly defined. We therefore reviewed our experience with postoperative
      angiography to determine its dangers and benefits. METHODS: During 10 years, 543
      consecutive patients received treatment for cerebral aneurysms. A retrospective
      analysis of 597 diagnostic angiograms obtained after aneurysm surgery for 494 of
      these patients was performed. RESULTS: Catheter-induced vessel spasm and
      dissection, occurring most frequently in the internal carotid artery, were
      observed in seven (1.2%) and six (1%) studies, respectively. No angiography
      associated strokes were identified. No association between age, smoking,
      hypertension, blood pressure, atherosclerosis, or severe vasospasm and
      angiographic complications was observed. Aneurysm remnants were identified in 36
      (5.7%) of the 637 aneurysms that were surgically treated. Atherosclerosis (P <
      0.01) or multiple clip applications (P < 0.01) were significantly associated with
      aneurysm remnants. Angiographic vessel occlusion was observed in 28 (5.7%)
      patients and resulted in stroke in 14 of these patients. Vessel occlusion was
      significantly associated with increasing aneurysm size (P < 0.001),
      atherosclerosis (P < 0.001), temporary clips (P < 0.001), multiple clips
      (P=0.03), multiple clip applications (P=0.001), and a new postoperative
      neurological deficit (P=0.002). Severe vasospasm and newly identified aneurysms
      were observed in 51 and 16 patients, respectively. CONCLUSION: Angiography after
      aneurysm surgery is safe and can be routinely performed. Angiography after
      aneurysm surgery should be particularly considered for patients with large
      aneurysms or cerebrovascular atherosclerosis and for those who develop new
      postoperative neurological deficits.

PMID- 9632183
TI  - Intra-arterially administered papaverine for the treatment of symptomatic
      cerebral vasospasm.
AB  - OBJECTIVE: We examined the therapeutic benefits of intra-arterially administered
      papaverine for treatment of symptomatic cerebral vasospasm after subarachnoid
      hemorrhage (SAH). Recent advances in microcatheter technology have facilitated
      endovascular approaches to vessels experiencing vasospasm after SAH. However,
      despite numerous encouraging anecdotal reports, no rigorous examination of the
      efficacy of these procedures has been published. Intra-arterial infusion of
      papaverine has become part of the standard management of vasospasm at some
      centers. METHODS: We examined a series of 31 patients undergoing papaverine
      infusion for the treatment of symptomatic vasospasm after SAH. The patients were
      a subgroup of the series enrolled in the North American Trial of Tirilizad for
      Aneurysmal Subarachnoid Hemorrhage. These individuals were matched with patients
      from the same trial who exhibited similar clinical characteristics (including the
      degree of vasospasm and the modified Glasgow Coma Scale scores measured at the
      time of admission and on the day of papaverine infusion) but received medical
      management alone for vasospasm. RESULTS: Logistic regression analysis comparing
      these two groups showed no statistical difference in the 3-month Glasgow Outcome
      Scale scores between patients receiving papaverine and control subjects (58%
      favorable outcomes for control subjects versus 45% for patients receiving
      papaverine). CONCLUSION: Although isolated series documenting clinical successes
      have prompted the increased use of papaverine as a treatment for vasospasm after
      SAH, this series suggests that, as it is currently being used, the drug does not
      provide added benefits, compared with medical treatment of vasospasm alone. This
      result does not preclude the possibility that alterations in the timing of or
      indications for drug treatment might produce beneficial effects.

PMID- 9632184
TI  - Metabolic profiles of patients with subarachnoid hemorrhage treated by early
      surgery.
AB  - OBJECTIVE: This study was conducted to evaluate the metabolic response of
      patients with subarachnoid hemorrhage (SAH) and to determine whether the severity
      of hemorrhage influenced the response. METHODS: Resting energy expenditure,
      nitrogen balance, and serum rapid-turnover proteins were studied for 3-day
      periods at Day 4, Day 10, and before discharge in patients with SAH who underwent
      surgical clipping within 2 days after the onset. The patients were divided into
      two groups according to the Hunt and Hess classification system; there were 17
      patients with Grade I or II (mild group) and 19 patients with Grade III, IV, or V
      (severe group). RESULTS: The mean resting energy expenditures (mean+/-standard
      deviation) were highest on Day 10, which were 146+/-24% and 198+/-78% of basal
      energy expenditure in the mild and severe groups, respectively. The nitrogen
      balance levels of the mild group on Days 4 and 10 were -3.0+/-3.5 g per day and 
      4.5+/-2.9 g per day, and those of the severe group were -7.5+/-3.2 g per day and 
      9.2+/-4.1 g per day, respectively. There was a significant difference in the
      nitrogen balance over time between the two groups (P=0.0037). Serum transferrin,
      prealbumin, and retinol-binding protein levels were lowest on Day 4 and gradually
      increased. There were no significant differences in these parameters between the
      two groups. CONCLUSION: SAH treated by surgery induces a profound stress
      response. A significant difference of increased catabolism but not decreased
      anabolism between the mild and severe groups was noted.

PMID- 9632185
TI  - Regional cerebral blood volume after severe head injury in patients with regional
      cerebral ischemia.
AB  - OBJECTIVE: Recent early cerebral blood flow (CBF) studies in cases of severe head
      injury have revealed ischemia in a substantial number of patients with a variety
      of computed tomographically demonstrated diagnoses. The underlying derangements
      causing this early ischemia are unknown, but cerebral blood volume (CBV)
      measurements might offer some insight into this pathological abnormality.
      METHODS: For this purpose, stable xenon-enhanced computed tomography was used for
      assessment of CBF, and a dynamic computed tomographic imaging technique was used
      for determining CBV. Based on the occurrence of regional ischemia (CBF < 20
      ml/100 g/min), seven patients with varying anatomic lesions revealed by computed
      tomography were identified for comparison between CBF and CBV in ischemic and
      nonischemic areas. RESULTS: Both CBF (15+/-4.3 versus 34+/-11 g/min, P < 0.002)
      and CBV (2.5+/-1.0 versus 4.9+/-1.9 ml/100 g) exhibited significantly lower
      values in the ischemic zones than in the nonischemic zones (means+/-standard
      deviations). Among 26 patients with or without ischemia observed during their
      initial follow-up studies, which were conducted between Days 2 and 8, all
      patients showed CBF and CBV values within the low-normal range. CONCLUSION: These
      data evidently support the suggestion that compromise of the microvasculature is
      the cause of early ischemia, rather than vasospasm of the larger conductance
      vessels.

PMID- 9632186
TI  - Venous air embolism in sitting and supine patients undergoing vestibular
      schwannoma resection.
AB  - OBJECTIVE: This study retrospectively compares the incidence of venous air
      embolism (VAE) detection and morbidity in the sitting and supine positions. All
      patients underwent vestibular schwannoma resection via the retrosigmoid approach
      by a single surgical team. METHODS: A total of 432 consecutive operations were
      reviewed, 222 of which were performed with the patients in the sitting position
      and 210 of which were performed with the patients in the supine position. Charts
      were reviewed for evidence of intraoperative VAE, intraoperative hypotension
      secondary to VAE, postoperative morbidity related to VAE, and other variables to
      compare the groups. RESULTS: This study demonstrated a 28% incidence of VAE
      detection when patients were in the sitting position compared to a 5% incidence
      of VAE detection when patients were in the supine position (P < 0.0001).
      Intraoperative hypotension secondary to VAE was noted in 1.8% of the sitting
      patients and 1.4% of the supine patients (P=0.72, no significant difference).
      Postoperative morbidity caused by VAE was noted in one sitting patient (0.5%)
      (pulmonary edema) and in no supine patients (P=0.48, no significant difference).
      Blood loss was slightly greater in the supine group, and operative times were
      similar in both groups, despite that the average tumor size of patients operated
      on in the sitting position was 2.8 cm versus 2.2 cm in the supine group (P <
      0.0001). CONCLUSION: Our results indicate that although there is a higher
      incidence of VAE detection in sitting patients, the morbidity is not
      statistically greater. We conclude that because morbidity from VAE is similar in
      either position, patient positioning should be based on surgical team preference.

PMID- 9632187
TI  - Endoscopic management of colloid cysts.
AB  - OBJECTIVE: Several surgical approaches have been proposed for the treatment of
      colloid cysts, which still remains controversial. The most recent technique used
      is endoscopy. By its nature, endoscopy cannot offer complete removal, as compared
      to microsurgical techniques, but can do more than puncture. To evaluate the
      usefulness of endoscopy for colloid cyst surgery, a series of 15 patients who
      were operated on for colloid cysts under endoscopic control since 1994 was
      reviewed. METHODS: The presenting symptoms of our patients (10 men and 5 women)
      were intermittent headache (10 patients), nausea (3 patients), short-term memory
      loss (4 patients), coma (2 patients), gait disturbance (3 patients), blurred
      vision (2 patients), and mental status changes (3 patients). The sizes of the
      cysts ranged from 4 to 50 mm (median, 22.93 mm). Depending on the radiological
      appearance, the procedure was performed via a right (10 patients) or left (5
      patients) precoronal burr hole. A rigid neuroendoscope was used. Initial
      stereotactic placement of the neuroendoscope was used in two patients who had
      moderate hydrocephalus. In the other patients, hand-guided endoscopy was
      performed using an articulated arm. The cysts were perforated with a needle. The
      opening was enlarged with microscissors. The cyst material was aspirated, and the
      remaining capsule was coagulated. RESULTS: The average follow-up was 15.26 months
      (range, 1-28 mo). Total aspiration of the cysts was achieved in 12 patients, as
      revealed by normal postoperative magnetic resonance imaging. Control magnetic
      resonance imaging revealed residual cysts in three patients. One patient
      presented with an asymptomatic recurrence at 1 year. Resolution of the symptoms
      was obtained in all patients except for two of the four patients with
      preoperative memory deficit (improvement without complete recovery). There was no
      mortality or morbidity. CONCLUSION: These results show that endoscopy is a safe
      and promising percutaneous technique for the treatment of colloid cysts of the
      third ventricle. Longer follow-up is, however, still required.

PMID- 9632188
TI  - Function-sparing surgery for desmoid tumors and other low-grade fibrosarcomas
      involving the brachial plexus.
AB  - OBJECTIVE: Low-grade fibrosarcomas and desmoid tumors present a surgical
      challenge in that they have a strong tendency for local invasion, surgical
      margins are poorly delineated, and complete resections are difficult. Nowhere is
      this more evident than in those lesions involving the brachial plexus. We review
      our experience with these difficult lesions. METHODS: From a prospective database
      of 2900 patients admitted for treatment of sarcoma between 1982 and 1996, we
      identified 15 patients with involvement of the brachial plexus by a low-grade
      fibrosarcoma or desmoid tumor. All patients underwent resection, with 13 of 15
      receiving adjuvant radiotherapy. The 15 patients had a mean age at initial
      operation of 47 years. The male-to-female ratio was 8:7. The mean follow-up
      period was 65 months (median, 53 mo). RESULTS: Gross total resection was achieved
      in 12 patients (80%), although 11 of these patients had positive surgical
      margins. Overall, 64% of the tumors have recurred locally. There were no distant
      metastases, and no patients died as a result of their disease. One patient died
      as a result of unrelated cancer. An assessment of the functional outcomes
      revealed seven patients with normal function or mild neurological deficits and
      eight who were suffering from significant weakness, debilitation, or chronic
      pain. One patient required forequarter amputation. CONCLUSION: Surgical resection
      plus postoperative radiotherapy is the treatment of choice for low-grade
      fibrosarcomas and desmoid tumors involving the brachial plexus. However,
      aggressive surgical management with the goal of achieving a gross total resection
      with negative histological margins can produce unnecessary morbidity. Preserving
      function should be a primary goal of the operations, although this will be
      associated with residual disease and will risk local recurrence but rarely death
      resulting from the disease.

PMID- 9632189
TI  - A mobile computed tomographic scanner with intraoperative and intensive care unit
      applications.
AB  - INTRODUCTION: A mobile computed tomographic scanner has been developed in which
      the scan plane is selected by means of gantry translation, rather than by
      translation of the patient table. This permits computed tomographic scanning in
      situ of any patient who is positioned on a radiolucent surface that fits within
      the inner diameter of the gantry. We report the design of and initial experience
      with this scanner as used with adapters for intraoperative and bedside computed
      tomography (CT). METHODS: The scanner is equipped with wheels, draws power from
      wall outlets (120 V, 20 A) in combination with batteries, and has a translating
      gantry. Preclinical studies of image quality were performed with phantoms. An
      operating table adapter was built for use with a radiolucent cranial fixation
      device. A bedside adapter was built that holds the head and shoulders of a
      patient in the intensive care unit. RESULTS: The preclinical phantom studies
      showed satisfactory image spatial resolution (0.8 mm) and low-contrast resolution
      signal-to-noise relative standard deviation (0.37%). Experience to date with 12
      patients has confirmed the feasibility of intraoperative CT on demand. Experience
      to date with 26 patients has confirmed the feasibility of routine bedside CT in
      the intensive care unit. CONCLUSION: With these adaptations, mobile CT may
      increase the efficiency of intraoperative scanning by making it available to
      multiple operating rooms without committing it to any room for an entire
      operation and may increase the efficiency and safety of CT of critically ill
      patients who currently need to leave the intensive care unit to travel to a fixed
      CT installation and back.

PMID- 9632191
TI  - Simultaneous somatosensory evoked potential and electromyographic recordings
      during lumbosacral decompression and instrumentation.
AB  - OBJECTIVE: Both motor and sensory neurological deficits have been reported after
      decompression and instrumentation of the lumbosacral spine. In this report, we
      describe a simple and effective method by which sensory and motor functions can
      be monitored simultaneously, using somatosensory evoked potentials (SSEP),
      spontaneous electromyographic (EMG) activity, and compound muscle action
      potential monitoring. The concomitant use of these monitoring techniques allows
      ongoing functional evaluation of the cauda equina and spinal cord during patient
      positioning, surgery, wound closure, and anesthetic emergence. METHODS: SSEPs
      were recorded continuously in response to peroneal or tibial nerve stimulation.
      EMG activity (both spontaneous and evoked) was recorded bilaterally from
      appropriate lower extremity muscle groups. All recordings (SSEP and EMG activity
      recordings) were obtained, stored, and reviewed simultaneously. RESULTS: SSEPs
      and EMG activity were simultaneously recorded for 44 patients. All patients in
      the study underwent surgical procedures to decompress and stabilize the
      lumbosacral spine, using pedicle screw instrumentation. In two cases, changes in
      SSEPs and spontaneous EMG activity were noted and were correlated with
      postoperative patient complaints. CONCLUSION: This report describes the
      concomitant use of powerful and simple tools that provide immediate, "early
      warning" feedback to the surgical team concerning the sensory and motor
      functioning of the spinal cord and cauda equina. In addition, compound muscle
      action potential recording provides a tool for the identification of both levels
      and structures in the lumbosacral spine.

PMID- 9632190
TI  - The asleep-awake-asleep anesthetic technique for intraoperative language mapping.
AB  - OBJECTIVE: We evaluated a combined technique designed for procedures requiring
      intraoperative language mapping. We planned to induce general anesthesia with
      endotracheal intubation and hyperventilation and then to awaken and extubate the
      patient for speech testing. After the latter, endotracheal reintubation and
      general anesthesia were planned. METHODS: With the patient under intravenously
      induced sedation, we topically anesthetized the airway with lidocaine that was
      delivered through a spraying catheter. Fiberoptic endotracheal intubation was
      then performed on the awake patient, using a modified endotracheal tube. General
      anesthesia with intravenous propofol or sodium thiopental was induced, the
      patient's head was attached to a Mayfield holder, and the pin and operative sites
      were infiltrated with 0.5% bupivacaine with epinephrine. In anticipation of
      speech mapping, general anesthesia was discontinued and lidocaine was injected
      into the catheter that was spirally attached to the endotracheal tube. After
      speech mapping, the awake patients were endotracheally intubated, guided with the
      fiberoptic laryngoscope or tube changer, and general anesthesia was induced and
      maintained until termination of the surgery. RESULTS: We did not observe any
      complications, such as coughing or head movements, during the preparation for
      general anesthesia, awakening and endotracheal extubation for speech mapping, and
      post-testing reintubation or induction of general anesthesia. CONCLUSION: The
      combined technique that we describe abolished the potential discomfort of
      surgical stimulation on a sedated patient, reduced the duration of wakefulness,
      and provided a secure airway and the means to hyperventilate our patients before
      dural opening.

PMID- 9632192
TI  - Extradural origin of the posteroinferior cerebellar artery: an anatomic study
      with histological and radiographic correlation.
AB  - OBJECTIVE: The posteroinferior cerebellar artery (PICA) usually arises from the
      intradural segment of the vertebral artery (VA). The extradural origin of the
      PICA is infrequent. Its preoperatory identification is important in surgical
      strategy during the exposure of the VA. METHODS: During an anatomic prosection,
      the VA was exposed at the craniocervical junction in cadaveric adult specimens.
      The extradural origin of the PICA was encountered bilaterally in one specimen and
      on one side in a second specimen. An anatomic study with histological and
      radiographic correlation was performed. RESULTS: Perforating branches originate
      from the PICA. They supply the middle and inferior third of the olive and the
      lateral aspect of the medulla. The PICA has cortical branches that lead to the
      cerebellum. Injury to the PICA can produce an infarction of these neural
      structures that can be asymptomatic or cause major neurological deficits.
      Radiographic results obtained using a lateral projection provided the most
      reliable delineation of the extradural origin of the PICA. When this artery
      originates at, or posterior to, the posterior aspect of the occipital condyle, an
      extradural origin is likely. CONCLUSION: Bilateral selective vertebral
      angiography should be performed with special attention to the relationships of
      PICA origins before any surgical exposure of the VA at the craniocervical
      junction, unless magnetic resonance angiography provides this information without
      question. A thorough understanding of the relative dominance of the VAs and
      PICAs, the location of the PICA origin, and the collateral circulation of the
      posterior fossa are prerequisites to surgery in this region. The preoperative
      identification of an extradural PICA is important in planning surgical strategy
      and in avoiding complications during operations near the foramen magnum.

PMID- 9632193
TI  - Manganese-metalloporphyrin (ATN-10) as a tumor-localizing agent: magnetic
      resonance imaging and inductively coupled plasma atomic emission spectroscopy
      study with experimental brain tumors.
AB  - OBJECTIVE: We examined whether selective tumor accumulation of a novel manganese
      metalloporphyrin (ATN-10) occurs in Fisher rats bearing intracerebral 9L gliomas.
      METHODS: After intravenous administration of ATN-10, magnetic resonance imaging
      of brains with tumors or nontumoral vasogenic brain edema was performed. Tissue
      manganese concentrations were measured by inductively coupled plasma atomic
      emission spectroscopy until 48 hours after administration of ATN-10, to evaluate
      its uptake in tumor, normal brain, and peritumoral brain tissue. RESULTS: In
      magnetic resonance imaging scans, early enhancement was observed in both tumor
      tissue and regions of nontumoral vasogenic brain edema at 5 minutes after ATN-10
      administration. However, delayed enhancement was noted only in tumor tissue, at
      24 hours after intravenous injection of ATN-10. Comparison of rat brain specimens
      and 24-hour magnetic resonance imaging scans revealed that only the viable
      portions of tumors were enhanced with ATN-10; necrotic regions and areas of
      peritumoral brain tissue and nontumoral vasogenic edema were not. Significantly
      greater uptake of ATN-10 was found in tumor samples, compared with normal and
      peritumoral brain tissue, at 24 hours. A high tumor/normal brain tissue ratio
      (10.4) was achieved at 24 hours. CONCLUSION: ATN-10, a manganese
      metalloporphyrin, is a potentially useful tumor-localizing agent that accumulates
      and is preferentially retained in viable tumor tissue.

PMID- 9632194
TI  - U74389G prevents vasospasm after subarachnoid hemorrhage in dogs.
AB  - OBJECTIVE: Oxygen-derived free radicals may contribute to vasospasm after the
      rupture of an intracranial aneurysm through direct vasoconstricting effects
      occurring within the arterial wall or, secondarily, by causing lipid peroxidation
      in the subarachnoid erythrocytes with secondary induction of vasoconstriction.
      U74389G is a potent inhibitor of lipid peroxidation and a scavenger of oxygen
      derived free radicals. This study determined the relative contributions of oxygen
      derived free radicals and lipid peroxidation to vasospasm in the double
      hemorrhage dog model. METHODS: Sixteen dogs underwent baseline (Day 0) cerebral
      angiography and induction of subarachnoid hemorrhage by two injections of blood
      into the cisterna magna 2 days apart. They were randomized to receive drug
      vehicle (n=8) or U74389G (n=8, 3 mg/kg of body weight/d) intravenously. Drug
      administration and end point analysis were blinded. The end points were
      angiographic vasospasm, as assessed by comparison of angiograms obtained before
      and 7 days after subarachnoid hemorrhage, and the levels of malondialdehyde and
      salicylate hydroxylation products (dihydroxybenzoic acids) in cerebrospinal fluid
      and of malondialdehyde in subarachnoid blood clots and basilar arteries 7 days
      after hemorrhage. RESULTS: Comparisons within groups of Day 0 and Day 7
      angiograms and between groups of angiograms obtained at Day 7, showed significant
      vasospasm in animals in the vehicle group (mean+/-standard error, 51%+/-4) but
      not in the U74389G group (25%+/-11, P < 0.05, unpaired t test). High-pressure
      liquid chromatographic assays of malondialdehyde and dihydroxybenzoic acids in
      cerebrospinal fluid, subarachnoid blood clots, and basilar arteries showed no
      significant differences between groups. CONCLUSION: The significant prevention of
      vasospasm by U74389G without change in levels of indicators of free radical
      reactions suggests that the effect of the drug is related to other processes
      occurring in the arterial wall and that cerebrospinal fluid levels of oxygen
      radicals and lipid peroxides are not useful markers of vasospasm.

PMID- 9632195
TI  - Effects of prelesioned peripheral nerve graft on nerve regeneration in the rat
      spinal cord.
AB  - OBJECTIVE: The aim of this study was to examine the effects of prelesioned
      peripheral nerve grafts on central nerve regeneration compared with the freshly
      transected peripheral nerve grafts in the dorsal funiculus of the rat spinal
      cord. METHODS: The experimental paradigm consisted of ligating the common
      peroneal nerve at the midthigh level for 7 days, while the adjacent tibial nerve
      was left intact. Numerous Schwann cells appeared accompanying regenerating axons
      in the proximal stump of the ligated nerve. The proximal stumps of the ligated
      (prelesioned) common peroneal nerve and the intact (untreated) tibial nerve were
      excised as one tissue block and autografted into the dorsal funiculi of the upper
      cervical cord. The graft was placed so that the prelesioned common peroneal nerve
      was positioned on the left dorsal funiculus and the untreated tibial nerve was
      positioned to the right of the midsagittal plane. Nerve regeneration was examined
      by light and transmission electron microscopy 1 to 16 weeks after grafting,
      comparing the effectiveness of prelesioned and untreated nerve grafts. RESULTS:
      Numerous regenerating axons were observed in the caudal border of both grafts 1
      to 2 weeks after grafting. Astrocyte proliferation was suppressed in the
      prelesioned grafts compared to the untreated grafts. Four to 16 weeks later, the
      number of regenerating axons was approximately 10-fold as large in the
      prelesioned grafts as in the untreated grafts. The regenerating axons were
      myelinated by Schwann cells. Astrocytic glial scar formation was inconspicuous in
      the prelesioned grafts, whereas it was prominent in the untreated grafts. Schwann
      cells were contiguous with astrocytes along regenerating axons, forming a
      continuous conduit from the central to peripheral nerve microenvironments for the
      outgrowth of regenerating axons. CONCLUSION: The prelesioned peripheral nerve
      graft is more effective than the untreated graft in suppressing astrocytic scar
      formation and in supporting the outgrowth of regenerating axons in the dorsal
      funiculus of rat spinal cord.

PMID- 9632196
TI  - Expression of c-Fos protein in the spinal cord after brachial plexus injury:
      comparison of root avulsion and distal nerve transection.
AB  - OBJECTIVE: Clinical reports indicate poor outcomes for avulsion injuries,
      compared with more peripheral nerve damage. These two different injuries may both
      affect gene expression in spinal neurons, and the changes in gene expression may
      be related to the types of injuries. METHODS: The brachial plexus of 48 adult
      male rats was lesioned by either root avulsion close to the spinal cord or distal
      nerve transection. The rats were quickly revived and remained awake until death
      at 30, 60, or 120 min after surgery. In rats with avulsive injuries, traumatic
      sites on the dorsal and ventral horns of the spinal cord were microscopically
      detected. Immunocytochemical analysis of the c-fos product was performed for the
      two experimental groups and for sham-treated control animals at the same survival
      times. RESULTS: An increase in Fos-like immunoreactivity (FLI) in cells of the
      spinal cord, at levels C4-T1, was detected at 30 min after nerve transection or
      root avulsion. The number of FLI-positive cells continued to increase at 60 and
      120 min after the nerve injury (P=0.001). FLI-positive cells were compared at the
      C7 level, in laminae 1 and 2, 3 and 4, and 5 to 10, after the two injuries and
      were found to be more abundant after the avulsive injury (P=0.0001); furthermore,
      the number of FLI-positive cells increased with time (P=0.001). In a comparison
      of all levels, both experimental groups demonstrated significantly greater
      numbers of FLI-positive cells than did controls, and the group with nerve root
      avulsion showed significantly (P=0.0001) more FLI-positive cells than did the
      group with distal nerve transection. CONCLUSION: These results suggest that nerve
      root avulsion from the spinal cord leads to increased and prolonged expression of
      c-fos and, potentially, greatly increased transcription of new messages for
      recovery, survival, or cell death.

PMID- 9632197
TI  - A combined surgical-endovascular device concept for giant aneurysm neck
      occlusion.
AB  - PURPOSE: In this report, we describe a new multimodality device concept for
      occluding giant aneurysms. The device is designed to exploit the advantages, and
      avoid the disadvantages, of conventional microneurosurgery and interventional
      neuroradiology methods. CONCEPT: Our device concept involves surgically placing
      small permanent magnets, incorporated into a partially occluded magnetic clip,
      about the extraluminal neck without mechanically compromising the perforating
      vessels. These magnets serve as optimally positioned anchor points for
      ferromagnetic materials subsequently introduced via the endovascular route.
      RATIONALE: Currently, neurosurgical extraluminal obliteration of giant aneurysms
      is achieved by mechanically closing the aneurysm neck with metal clip blades,
      which is a technique that risks inadvertent occlusion of critical perforating
      vessels. Perforating vessel strokes can largely be avoided using endovascular
      aneurysm occlusion methods. However, in the setting of the giant aneurysm, these
      endovascular techniques are associated with high rates of incomplete occlusion.
      DISCUSSION: Preliminary feasibility tests of this concept were conducted using a
      simple prototype constructed in our laboratories.

PMID- 9632198
TI  - Orbitocranial penetration by a fern: case report.
AB  - OBJECTIVE AND IMPORTANCE: Cranial and orbitocranial penetration by organic
      foreign material is not infrequent. It is important to identify whether
      penetration has occurred and to localize and remove the organic foreign material.
      CLINICAL PRESENTATION: We report a 15-month-old patient who suffered
      orbitocranial penetration with the stem of a fern. The stem passed through the
      orbit, exiting via the superior orbital fissure. It continued through the middle
      cranial fossa to end in the posterior cranial fossa. INTERVENTION: The patient
      underwent surgery, and a modified Dolenc procedure was performed. The foreign
      body was identified in the prepontine cistern and was removed. An extradural
      approach was performed to the cavernous sinus and superior orbital fissure, and
      the remaining foreign body was removed. CONCLUSION: Retained intracranial wood
      should be removed. The radiological diagnosis can be difficult, and magnetic
      resonance imaging is the investigation of choice. Magnetic resonance imaging may
      not detect some cases of organic foreign material penetration.

PMID- 9632199
TI  - Sphenoid sinus brown tumor of secondary hyperparathyroidism: case report.
AB  - OBJECTIVE AND IMPORTANCE: Brown tumor is a misnomer for a reparative cellular
      process caused by primary or, less commonly, secondary or tertiary
      hyperparathyroidism. Atypical involvement of the base of the cranium in the area
      of the sphenoid sinus and the orbit is exceedingly rare and may produce a
      neurological deficit as a primary clinical presentation. Those neurosurgeons
      dealing with cranial base and pituitary lesions should be aware of this disease
      entity, and it should be listed in the differential diagnosis. CLINICAL
      PRESENTATION: A 21-year-old woman with end-stage renal failure on chronic
      dialysis was referred to the Department of Neurosciences at King Faisal
      Specialist Hospital and Research Centre with a 4-month history of progressive
      impairment of vision, associated with headache and nausea. Computed tomography
      and magnetic resonance imaging demonstrated an expansive mass lesion in the
      sphenoid sinus with erosion of the sellar floor and posterior medial wall of the
      orbit causing compression of the optic nerves. The biochemical laboratory studies
      showed elevation of parathyroid hormone and confirmed the diagnosis of
      hyperparathyroidism. INTERVENTION: The transnasal-transsphenoidal approach was
      used for extensive microsurgical removal of the lesion. The postoperative course
      was uneventful, and the improvement in vision was dramatic. CONCLUSION: Brown
      tumor, although rare, should be listed in the differential diagnosis of expansive
      mass lesions in the area of the sphenoid sinus and cranial base. The management
      is multidisciplinary, and therapeutic options should target the underlying cause.

PMID- 9632200
TI  - Shunt-related abdominal metastasis of cerebral teratocarcinoma: report of an
      unusual case and review of the literature.
AB  - OBJECTIVE AND IMPORTANCE: Internal drainage of cerebrospinal fluid to the
      abdominal cavity via a ventriculoperitoneal shunt (VPS) is a common procedure for
      therapy of obstructive hydrocephalus; because this condition is often caused by
      brain tumors blocking the natural cerebrospinal fluid pathways, the VPS as an
      artificial anastomosis can provide the means for the spreading of tumor cells by
      the cerebrospinal fluid. We report the case of a VPS-related abdominal metastasis
      of a teratocarcinoma and review the pertaining literature. CLINICAL PRESENTATION
      AND INTERVENTION: A 24-year-old man with a history of three brain tumors that
      were operated on when the patient was 14, 21, and 23 years of age developed an
      acute ileus 7 months after VPS insertion for cerebral teratocarcinoma.
      Intraoperatively, a massive abdominal tumor was observed, which turned out to be
      a peritoneal metastasis of the aforesaid brain tumor. The patient died as a
      result of his illness 1 month later. RESULTS: To date, 58 VPS-related metastases
      of brain tumors have been described. The male-to-female ratio is 1.6:1, the mean
      age at shunt insertion is 12.2 years, and the interval between shunt operation
      and diagnosis of metastases is 16.8 months. During the observation time, 69.2% of
      the patients died as a result of their illness or abdominal metastases. The most
      common sources of the metastases were germinomas (27.7%), medulloblastomas
      (19.1%), and endodermal sinus tumors (10.3%). CONCLUSION: The presented case is
      only the second VPS-related abdominal spreading of a cerebral teratocarcinoma.
      Metastases via VPS are rare but should be considered as a possible complication
      and mode of systemic spread in patients with primary intracranial malignancy.

PMID- 9632201
TI  - Spontaneous chronic epidural pneumocephalus resulting from hyperpneumatization of
      the cranium causing mass effect: case report.
AB  - OBJECTIVE AND IMPORTANCE: We report a rare case of spontaneous epidural
      pneumocephalus resulting from an unusual boney defect caused by
      hyperpneumatization of the cranium. The pneumocephalus was also unusual for its
      chronicity and significant mass effect. CLINICAL PRESENTATION: A 49-year-old man
      presented with a 3-year history of diffuse headaches and sensation of air
      movement in his sinuses on the right side. An evaluation for suspected sinusitis
      using computed tomography determined extensive pneumatization of most of the
      cranium, a large accumulation of epidural air, and a critical degree of brain
      shift. INTERVENTION: A right frontoparietal-temporal craniotomy with an
      osteoplastic bone flap was performed. The floor of the middle cranial fossa and
      the inner table of the bone flap were extensively debrided of air cells. A large
      pericranial flap was turned down over the floor of the middle cranial fossa and
      was held in place by a fat graft. After closing the craniotomy, a tympanostomy
      tube was placed into the right tympanic membrane. CONCLUSION: The incidence of
      hyperpneumatization of the cranium seems to be very low. Hyperpneumatization when
      present, however, can cause spontaneous intracranial pneumocephalus. Based on the
      literature and the success of this case, the optimal management is surgical
      obliteration of the involved air cells.

PMID- 9632202
TI  - Acquired dural arteriovenous malformations of the lumbar spine: case report.
AB  - OBJECTIVE AND IMPORTANCE: Although dural arteriovenous malformations (AVMs) are
      considered to be acquired, no conclusive evidence has been obtained. The first
      case of dural AVMs of the lumbar spine that showed evidence supporting their
      being acquired lesions is described. CLINICAL PRESENTATION: A 27-year-old man was
      admitted to our hospital in November 1994, presenting with increasing pain and
      numbness in the left buttock to the left lower limb. Myelography and
      arteriography showed dural AVMs of the lumbar spine. However, the myelogram
      obtained before surgery for lumbar disc herniation in 1987 provided no findings
      suggestive of intradural vascular anomalies. INTERVENTION: Embolization
      procedures via the left iliolumbar arteries were performed. However, there was no
      improvement of the symptoms, and the patient underwent surgical treatment.
      CONCLUSION: The present report documents a case of dural AVMs of the lumbar spine
      that showed evidence supporting their being acquired lesions.

PMID- 9632203
TI  - Retethering of sectioned fibrolipomatous filum terminales: report of two cases.
AB  - OBJECTIVE AND IMPORTANCE: The release of a tethered spinal cord by sectioning a
      thickened filum terminale is a straightforward surgical procedure that can
      prevent, arrest, or ameliorate neurological deficits. We recently recognized
      progressive neurological deterioration caused by filum retethering in two
      patients years after this procedure was performed. This sequela of a recurrent
      tethered cord after the sectioning of a filum terminale has not previously been
      described. CLINICAL PRESENTATION: Two female patients, each 13 years of age at
      presentation, had been previously operated on for tethered spinal cords secondary
      to fibrolipomatous (fatty) fila terminale. Both presented with bladder
      dysfunction and one with progressive paraparesis. Magnetic resonance images
      revealed a low-lying conus medullaris and a sectioned filum with the proximal
      stump adherent to the posterior dura. INTERVENTION: Each patient underwent
      neurosurgical exploration of the previous site of sectioning, with the
      recognition of a retethered proximal stump of the filum terminale. After
      rerelease of the fatty filum, the patient with only bladder dysfunction
      stabilized and a motor examination revealed normal results for the patient with
      progressive paraparesis. CONCLUSION: Retethering of the spinal cord is a rare
      sequela after the sectioning of a tight filum terminale. The clinical
      presentation is typical for recurrent cord tethering, and the radiographic
      findings are subtle. Careful surgical exploration should be offered for spinal
      cord untethering. Awareness of this rare and hitherto undescribed sequela is
      necessary for appropriate long-term management of tethered spinal cord caused by
      a fatty filum terminale.

PMID- 9632204
TI  - Endovascular coil occlusion of a traumatic basilar-cavernous fistula: technical
      report.
AB  - OBJECTIVE AND IMPORTANCE: We describe an unusual case of an 8-year-old male
      patient presenting with a traumatic basilar artery aneurysm associated with a
      basilar-cavernous fistula. CLINICAL PRESENTATION: The fistula occurred as the
      result of an accident involving a vehicle and a pedestrian. The patient
      originally presented in a coma and with a dense left hemiparesis. INTERVENTION:
      The traumatic basilar aneurysm and basilar-cavernous fistula were successfully
      occluded by endovascular coil embolization in two sessions. By 6 months after
      injury, the patient had made an excellent neurological recovery, requiring only a
      left leg brace for walking. CONCLUSION: Endovascular coil embolization provided
      an effective treatment option in the case of this complex and unusual
      arteriovenous fistula. We discuss the radiological and clinical features of
      related traumatic neurovascular lesions.

PMID- 9632206
TI  - Smoking and the human vertebral column: a review of the impact of cigarette use
      on vertebral bone metabolism and spinal fusion.

PMID- 9632205
TI  - Extraction of broken pedicle screws: technical note.
AB  - OBJECTIVE: To describe a simple technique for extraction of broken pedicle screw
      fragments using a high-speed drill and to discuss additional extraction
      techniques presented in the literature. TECHNIQUE: The broken pedicle screw is
      removed by drilling a pilot hole with a side-cutting bit next to and along the
      long axis of the fragment in the superior aspect of the pedicle. The bit is then
      wedged into the interface between the bone and the proximal screw threads. While
      the bit is pressed against the threads, the drill is activated in brief pulses.
      The clockwise rotation of the drill bit engages the threads and backs out the
      screw fragment RESULTS: This technique has been successfully used in at least two
      patients with fractured titanium screws allowing placement of larger diameter
      screws in the same holes. Standard equipment was used, and no complications were
      encountered. CONCLUSION: Broken titanium pedicle screws can be extracted without
      damaging the pedicle and without using specialized equipment.

PMID- 9632207
TI  - Acoustic neuromas: results of current surgical management.

PMID- 9632208
TI  - Steroids and gunshot wounds to the spine.

PMID- 9632209
TI  - Intramedullary pressure in syringomyelia: clinical and pathophysiological
      correlates of syrinx distension.

PMID- 9632210
TI  - Complications in patients with palmar hyperhidrosis treated with transthoracic
      endoscopic sympathectomy.

PMID- 9632211
TI  - Chronic ethanol consumption impairs spatial remote memory in rats but does not
      affect cortical cholinergic parameters.
AB  - We have studied learning, memory and cortical cholinergic parameters after oral
      administration of 20% v/v ethanol solution to male Fisher rats for 6 months. A
      group of rats were trained to behave efficiently in an eight-arm radial maze and
      after that split into two subgroups submitted to ethanol or control treatment.
      Ethanol-treated rats had more difficulty in relearning the same task 1 year
      later, compared to ethanol-untreated rats (control). Differences in working
      memory performance were found, but only in the first 10 training sessions.
      Another group of rats, which had not been pretrained, was also split into two
      subgroups submitted to ethanol or control treatment. After that, these rats were
      trained in the radial maze task for the first time. No significant difference was
      found between the reference memory performance of the untreated subgroup and the
      treated one. These two subgroups did not significantly differ in their working
      memory performance either. Moreover, there were no significant differences
      between treated and control subjects in the following biochemical brain cortical
      parameters: in vitro acetylcholinesterase (AChE) activity, and stimulated
      acetylcholine (ACh) release. This work presents an experimental design that
      allows assessment of remote memory performance after ethanol chronic consumption
      and shows that the experimental subject is able to retain the behaviors learned 1
      year before. It was concluded that chronic ethanol treatment may cause retrograde
      amnesia, which does not seem to be linked with a cortical cholinergic deficit.

PMID- 9632212
TI  - Hypothermic effects of dopamine D3 receptor agonists in the island of Calleja
      Magna. Potentiation by D1 activation.
AB  - The selective functions of D3 receptors in the brain are still poorly understood,
      mainly because all the ligands active at dopamine D3 receptors have also a high
      affinity for the D2 receptors. However, it is possible to study selectively D3
      receptor function because some brain structures, such as the islands of Calleja,
      contain D3 and not D2 receptors. The position of the island of Calleja Magna in
      the rat brain makes it possible to inject dopamine D3 ligands into the vicinity
      of these D3 receptors, and to study their behavioral role, with no concomitant
      action on D2 receptors. We studied the effects on body temperature and on
      locomotion of unilateral microinjections of D2/D3 receptors ligands into the
      island of Calleja Magna and into the adjacent nucleus accumbens. The results show
      that D3 agonists injected into the island of Calleja Magna decrease body
      temperature and that this effect is potentiated by simultaneous injection of the
      D1 agonist SKF 38393. D3 agonists have no effect on locomotor activity in the
      island of Calleja Magna. In the nucleus accumbens, the D3 agonists have only weak
      effects on body temperature, but, when associated with a D1 agonist, strongly
      stimulate locomotor activity. The effects on body temperature of unilateral
      microinjections of dopamine agonists into unilaterally dopamine-depleted animals
      are the same as those in nondepleted ones. This indicates that the D3 receptors
      are localized postsynaptically in the island of Calleja Magna.

PMID- 9632213
TI  - The anxiogenic agents, yohimbine and FG 7142, disrupt the noradrenergic response
      to novelty.
AB  - Whether or not abnormal noradrenergic transmission can be a causal factor in
      anxiety is controversial. The present experiments examined this question by
      comparing the effects of two anxiogenic agents on noradrenaline efflux in the
      frontal cortex of freely moving rats. A single anxiogenic dose of either
      yohimbine (2.5 or 5 mg/kg) or FG 7142 (10 or 20 mg/kg) was administered to rats
      by i.p. injection. Yohimbine increased spontaneous efflux of noradrenaline, but
      FG 7142 had no effect. However, subsequent exposure of rats to a novel
      environment increased noradrenaline efflux in vehicle-, but not drug-treated
      rats. Calculation of the net change in noradrenaline efflux caused by transfer to
      the novel environment showed that this was reduced by yohimbine, whereas FG 7142
      increased it. These two compounds also had different effects on locomotor
      activity in the novel environment. The results suggest that anxiety is unlikely
      to be invariably associated with increased noradrenergic transmission, in the
      frontal cortex at least. However, it remains possible that any disruption of the
      noradrenergic response to stress could be an underlying feature of anxiety.

PMID- 9632214
TI  - Maturation of the biphasic behavioral and heart rate response in the formalin
      test.
AB  - The biological processes that mediate and modulate the perception of pain in the
      infant animal are not well studied and thus nociception during early development
      is poorly understood. In the adult animal, injection of formalin into the hind
      paw produces distinct phases of behavioral and autonomic responses: an early
      nociceptive response followed by a period of quiescence and a later second phase
      that matches or exceeds the initial response. The delayed reaction of the second
      phase has been suggested to be a model of inflammation-induced changes in
      neuronal sensitivity. Studies in the infant rat have demonstrated that the first
      phase is present in the fetus and neonate but the onset of the second phase is
      later maturing. We report here that the first phase occurs in 7- to 35-day-old
      pups in the formalin test when measured behaviorally and in 14- to 35-day-old
      pups when assessed by increased heart rate. However, the behavioral response in
      second phase is greatly attenuated or absent in 7- or 14-day-old pups, a finding
      consistent with that of others, appearing first at 21 days of age. The biphasic
      tachycardic response was not noted until even later, at 35 days of age. These
      data confirm that the neural mechanisms that mediate the secondary behavioral
      phase in the formalin test are late maturing, that the biphasic cardiovascular
      response does not occur until substantially later, after weaning, and that the
      behavioral and cardiovascular responses are dissociated developmentally.

PMID- 9632215
TI  - Ameliorating effect of p-hydroxybenzyl alcohol on cycloheximide-induced
      impairment of passive avoidance response in rats: interactions with compounds
      acting at 5-HT1A and 5-HT2 receptors.
AB  - The effect of p-hydroxybenzyl alcohol (HBA) on cycloheximide (CXM)-induced
      impairment in the step-through passive avoidance task was investigated in rats
      and compared to the effect of the nootropic piracetam. HBA and piracetam
      significantly counteracted the CXM-induced shortening of retention latencies. The
      effect of HBA was a bell-shaped dose-response curve with a maximal effect of 5
      mg/kg. The counteractive effect of HBA was not depressed by either scopolamine or
      mecamylamine. The serotonin (5-HT) releaser, p-chloroamphetamine, and presursor,
      5-hydroxytryptophan, significantly antagonized the counteractive effect of HBA on
      the CXM-induced shortening of retention latencies. Furthermore, the counteractive
      effect was also inhibited by the 5-HT1A receptor agonist 8-hydroxy-2-(di-n
      propylamino)tetralin (8-OH-DPAT) and the 5-HT2 receptor agonist 1-(2,5-dimethoxy
      4-iodophenyl)-2 aminopropane [(+/-)-DOI], but potentiated by the 5-HT1 receptor
      antagonist (+/-)-pindolol and the 5-HT2 receptor antagonist ritanserin. There
      results suggest that the beneficial effect of HBA on CXM-induced impairment is
      amplified by treatment with serotonergic receptor antagonists but reduced by
      serotonergic 5-HT1A and 5-HT2 receptor agonists, and insensitive to cholinergic
      manipulations.

PMID- 9632216
TI  - Isradipine combined with naltrexone persistently reduces the reward-relevant
      effects of cocaine and alcohol.
AB  - Previous studies have revealed that the combination of small doses of isradipine
      and naltrexone (ISR&NTX) blocks the ability of cocaine to enhance pressing for
      rewarding, lateral hypothalamic brain stimulation. Further, such combinations
      also reduce rats' intakes of alcoholic beverages. Here, we asked whether ISR&NTX
      would lose its ability to reduce the reinforcing effects of cocaine and alcohol
      when given daily. Specifically, after almost 2 months of daily injections,
      ISR&NTX blocked the expression of a cocaine-induced conditioned place preference
      (CPP). By themselves, ISR and NTX were not effective at blocking cocaine's
      effects. Subsequent to the CPP procedures, the rats continued to receive daily
      injections for another 3 weeks. During this time, they were given access to water
      and an alcoholic beverage for 2 h a day. As expected, placebo controls gradually
      increased their daily intakes until they were taking about 2 g/kg of ethanol
      daily. ISR, NTX, and ISR&NTX blocked the typical pattern of intakes. At the end
      of the 3-week period, the rats had received 80 consecutive daily injections. The
      data suggest that the salient effects of ISR&NTX do not wane. The data support
      the idea that ISR&NTX would be a useful pharmacotherapy for poly drug abuse.

PMID- 9632217
TI  - Effects of heroin/cocaine combinations in rats trained to discriminate heroin or
      cocaine from saline.
AB  - The effects of heroin and cocaine administered alone or in combination were
      examined in rats trained to discriminate either heroin (0.56 mg/kg i.p.; n = 6)
      or cocaine (5.6 mg/kg i.p.; n = 6) from saline. Heroin (0.032-1.8 mg/kg)
      substituted completely for the heroin training stimulus in all six heroin-trained
      rats, but failed to substitute for cocaine in any of the cocaine-trained rats.
      Cocaine (0.1-32 mg/kg) substituted completely for the cocaine training stimulus
      in all six cocaine-trained rats, and substituted for heroin in two of six heroin
      trained rats. The opioid antagonist naltrexone (0.01-1.0 mg/kg) antagonized the
      discriminative stimulus effects of heroin, but naltrexone at doses up to 10 mg/kg
      had no effect on the discriminative stimulus effects of cocaine. The dopamine
      receptor antagonist flupenthixol (0.032-0.56 mg/kg) attenuated the discriminative
      stimulus effects of heroin and completely blocked the discriminative stimulus
      effects of cocaine. When heroin-cocaine combinations were administered to the
      heroin-trained rats, cocaine (1-5.6 mg/kg) did not significantly alter the mean
      heroin dose-effect curve. Similarly, in the cocaine-trained rats, heroin (0.1
      0.56 mg/kg) did not significantly alter the mean cocaine dose-effect curve. These
      results suggest that combinations of heroin and cocaine usually produce
      discriminative stimulus effects similar to either heroin or cocaine alone.

PMID- 9632218
TI  - Potential serotonergic interactions with the anxiolytic-like effects of calcium
      channel antagonists.
AB  - In a series of experiments, we investigated the interaction between the calcium
      channel antagonist, nifedipine, and the 5-HT1A agonist, ipsapirone. In the first
      experiment, we demonstrated that nifedipine (20 mg/kg), and to a lesser extent
      nimodipine (20 mg/kg), exerted an anxiolytic-like effect as did diazepam (5
      mg/kg) in an experimental paradigm based on water consumption in a novel
      environment. In the second experiment, nifedipine (1.25, 2.5, and 5 mg/kg), and
      in the third experiment, ipsapirone (1.5. 3.0, and 6.0 mg/kg), have been found to
      exert a dose-dependent effect in the same test. Finally, a small and ineffective
      dose of ipsapirone (1.5 mg/kg) potentiated the anxiolytic-like effect of various
      doses of nifedipine. The data obtained are discussed in terms of the potential
      anxiolytic-like action of calcium channel antagonists and in relation to their
      electrophysiological effects. Moreover, the interaction between ipsapirone and
      nifedipine is discussed in terms of the possible involvement of central
      serotonergic systems in the behavioral effects of the calcium channel
      antagonists.

PMID- 9632219
TI  - Ovariectomy-induced hyperalgesia and antinociceptive effect of elcatonin, a
      synthetic eel calcitonin.
AB  - Using ovariectomized (OVX) rats in the tail-withdrawal nociceptive test, we
      examined OVX-induced hyperalgesia and the antinociceptive effect of
      subcutaneously administered elcatonin, a synthetic derivative of eel calcitonin
      ([Asu1.7] eel calcitonin). Because tail-withdrawal latency was significantly and
      continuously reduced and bone mineral density decreased in OVX rats compared with
      those of sham-operated rats, it was demonstrated that ovariectomy induced
      prolonged hyperalgesia and osteoporosis. After repeated administrations for 3 or
      4 weeks, subcutaneously injected elcatonin increased the latency of the OVX rats
      in a dose-dependent manner, compared to the vehicle-treated OVX rats. At a dose
      of 20 U/kg/day, there were significant differences (p < 0.01) in the latency
      between the elcatonin- and vehicle-treated OVX rats. This effect of elcatonin was
      completely inhibited by p-chlorophenylalanine treatment, suggesting that the
      central serotonergic system may be involved in the elcatonin antinociception of
      OVX-induced hyperalgesia.

PMID- 9632220
TI  - Comparative studies of huperzine A, E2020, and tacrine on behavior and
      cholinesterase activities.
AB  - Comparative effects of cholinesterase inhibitors (ChEI) huperzine A with E2020
      and tacrine on the radial maze performance in ethylcholine mustard aziridinium
      ion (AF64A)-treated rat and inhibition of cholinesterase activity were studied.
      The intracerebroventricular (i.c.v.) injection of AF64A (3 nmol/side) caused
      significant impairment in the rat's ability to fulfill the partially baited maze
      paradigm. Oral huperzine A (0.5-0.8 mg/kg), E2020 (1.0-2.0 mg/kg), and tacrine
      (8.0 mg/kg) effectively reversed AF64A-induced working memory deficit. The doses
      that improved AF64A-induced memory deficit were correlated to about 25-30%
      (huperzine A) and less than 10% (E2020, tacrine) inhibition of
      acetylcholinesterase (AChE) activity in the cortex and hippocampus. Huperzine A,
      E2020 and tacrine all produced dose-dependent inhibition of brain AChE following
      i.c.v. and oral administration. Oral huperzine A exhibited higher efficacy on the
      inhibition of AChE in the cortex and hippocampus than those of E2020 and tacrine.
      Tacrine was more effective in inhibiting plasma butyrylcholinesterase (BuChE)
      than it was brain AChE. Conversely, the BuChE activity was less affected by
      huperzine A and E2020. The results showed that huperzine A had high
      bioavailability and more selective inhibition on AChE activity in cortex and
      hippocampus. Huperzine A fits more closely with the established criteria for an
      ideal AChE inhibitor to be used in clinical studies.

PMID- 9632221
TI  - Sparing by rasagiline (TVP-1012) of cholinergic functions and behavior in the
      postnatal anoxia rat.
AB  - Rasagiline (N-propargyl-1(R)aminoindan) is a selective and potent MAO-B inhibitor
      currently under development as the mesylate salt (TVP-1012) for the treatment of
      various neurologic disorders. Preliminary work in adult and senescent rats,
      either normal or hypoxia-lesioned, showed that chronic rasagiline treatment
      improved performance in memory and learning tasks, suggesting some beneficial
      effect on central cholinergic function. We have now used the postnatal anoxia
      lesioned rat as a model of cholinergic dysfunction. In the neonatal rat, anoxia
      strongly affects the cholinergic system, which has not yet reached full
      maturation at this state of life. Rasagiline mesylate was administered from day 1
      to completion of the study (day 60), first through nursing mother milk until
      weaning (day 21), then in drinking water, at the rate of 0.5 mg/kg/day. Drug
      access to the CNS was verified by analysis of MAO activity in brain (at 21 days).
      Treatment improved the juvenile hyperactivity syndrome associated with anoxia (at
      day 28). It improved performance in the passive avoidance test to normal control
      level (at day 40). It improved spatial memory performance in the Morris water
      maze to normal control level (at day 50). The untreated anoxia group failed in
      these tasks and was significantly inferior to either the normal control and
      rasagiline-treated anoxia groups. Determination of ChAT activity in the caudate
      and hippocampus of rats from each of these groups gave the following results
      (pmol ACh/mg protein/min). Caudate: normal control, 588 +/- 56; anoxia, 398 +/-
      54; rasagiline-treated anoxia, 536 +/- 35. Hippocampus: normal control, 380 +/-
      31; anoxia, 275 +/- 47; rasagiline-treated anoxia, 325 +/- 35. Results are mean
      +/- SD from each of seven to nine different donors in a group. Thus, improvement
      in memory and learning tasks of the rasagiline-treated anoxia group finds
      correspondence in the activity of the cholinergic marker ChAT in two brain
      regions that have prominent cholinergic innervation.

PMID- 9632222
TI  - Cocaine sensitization can accelerate the onset of peak cocaine behavioral
      effects.
AB  - The development of sensitization to the behavioral effects of cocaine occurs with
      repeated intermittent usage. In the present study rats were given five daily i.p.
      injections of cocaine (10 mg/kg) immediately prior to placement in an open-field
      environment for 20 min to induce cocaine sensitization. Control groups received
      saline injections or cocaine injections (10 mg/kg) 30 min after testing in the
      home cage. One week later the animals were given a challenge test with 10 mg/kg
      cocaine. The animals that had received cocaine in the test environment exhibited
      a more rapid onset of cocaine-induced behavioral effects than either animals
      previously treated with saline or animals that had received cocaine in the home
      cage. In a second experiment, the same sensitization protocol was followed except
      that during the interval between the end of the cocaine/saline treatments and the
      challenge test, the animals were given six daily 20-min saline tests to assess
      the contribution of differential habituation and/or Pavlovian conditioning to the
      sensitization effect. Neither habituation or Pavlovian conditioning altered the
      more rapid onset of cocaine stimulant effects induced by repeated cocaine
      treatments. It is suggested that the faster onset of cocaine effects is another
      way in which cocaine sensitization contributes to cocaine abuse liability.

PMID- 9632223
TI  - Naltrexone and amperozide modify chocolate and saccharin drinking in high alcohol
      preferring P rats.
AB  - Previous studies showed that the 5-HT2 receptor antagonist, amperozide, is
      somewhat more potent than the opiate antagonist, naltrexone, in reducing alcohol
      drinking in high alcohol-preferring (P) rats. The purpose of this study was to
      determine in the P rat whether the effect of either drug could be due, in part,
      to an alteration in gustatory function. In an unlimited, 24-h free choice
      paradigm, P rats were offered water simultaneously with either a highly palatable
      0.1% saccharin solution or a 1:4 dilution of Nestle Sweet Success chocolate
      drink. Throughout all phases of the study, the P rats always consumed
      significantly greater volumes of the chocolate drink than of the saccharin
      solution, i.e., 526 ml/kg vs. 181 ml/kg, respectively. Successive 12-day
      experimental periods consisted of three phases: a 4-day predrug control interval;
      4 days of administration of saline control vehicle or either drug; and a final 4
      day postdrug interval. In a counterbalance design, saline, amperozide (1.0 or 5.0
      mg/kg) or naltrexone (2.5 or 5.0 mg/kg) was administered subcutaneously twice
      daily at 1600 and 2200 h for 4 days. Amperozide and naltrexone significantly
      reduced the drinking of chocolate in a dose-dependent manner. Conversely, only
      the two higher doses of amperozide and naltrexone decreased the intake of
      saccharin significantly. Thus, these findings suggest that different populations
      of central serotonin and opioid receptors concurrently underpin, in part, the
      preferences for both palatable and/or nutrient fluids. Finally, because both the
      opiate and 5-HT2A antagonists reduce the ingestion of saccharin and chocolate
      solutions differentially, it is apparent that preferences for alternative
      palatable fluids should be examined when candidate drugs are screened for
      suppressing alcohol drinking and ultimately the treatment of alcohol abuse.

PMID- 9632224
TI  - Training dose and session time as contextual determinants of heroin self
      administration in rats.
AB  - In this study a rat self-administration model was used to examine the effects of
      training dose and time in the session on the dose-effect curve for heroin. Doses
      of heroin lower than 5.4 microg/inf maintained higher rates of drug intake in
      animals trained with 5.4 microg/inf compared to 18 microg/inf. Doses greater than
      5.4 microg/inf maintained similar rates of intake in both groups of animals. The
      dose-response curve was shifted downward and to the right as the session
      progressed for animals trained with 5.4 microg/inf of heroin; however, the shift
      in the dose-intake curve over the session was less pronounced when the training
      dose was 18 microg/inf. Naltrexone and naltrindole were administered to animals
      in which responding was engendered with infusions of 5.4 microg of heroin to
      determine the effects of these antagonists in the context of time is the session.
      The potency of naltrexone decreased across the 4 h of the session with a time
      course that was consistent with literature reports on the elimination kinetics of
      naltrexone in rat brain. In contrast, there was not a significant interaction
      between naltrindole dose and session time. Therefore, the rates of heroin intake
      in rats are dependent not only upon the dose available for self-administration,
      but upon the session time and training dose as well.

PMID- 9632225
TI  - A new look at an old task: advantages and uses of sickness-conditioned learning
      in day-old chicks.
AB  - In sickness-conditioned learning, animals become ill after sampling a new
      substance and develop an aversion that is expressed as avoidance of that
      substance in subsequent presentations. We examined the parameters of a one-trial,
      nongustatory, sickness-conditioned learning task in day-old chicks. Chicks pecked
      a bead and were made ill by i.p. injection of lithium chloride (LiCl). Both 0.5
      and 1.0 M LiCl (0.1 ml) produced reliable avoidance at test. Chicks injected with
      LiCl between 15 and 45 min after training avoided the bead at test, whereas those
      injected within 5 or 10 min or more than 45 min after training did not. Avoidance
      was present until 24 h posttraining and absent after 48 h. Therefore, robust
      learning of the sickness-conditioned learning task occurs in one trial without
      the need for gustatory cues, and memory for the task lasts at least 24 h. Uses of
      this task to study memory formation in the day-old chick are discussed.

PMID- 9632226
TI  - Comparison of behavioral effects of moclobemide and deprenyl during forced
      swimming.
AB  - The present study compared the antiimmobility effects of l-deprenyl (DEP) and
      moclobemide (MOC) to the classic antidepressant imipramine (IMI), using an
      ethological approach. To investigate the degree of MAO-B inhibition by DEP and
      MOC, combination of treatments of ineffective doses of phenylethylamine (PHEA)
      with DEP or with MOC were administered in three doses before immobility was
      tested in the forced-swimming paradigm. Tests were videotape recorded for
      analysis of the frequency and duration of the behaviors during the procedure.
      There was a significant, dose-dependent decrease in immobility duration and an
      increase in mobility duration of rats treated with IMI. Both active behaviors of
      climbing and swimming were equally enhanced by the tricyclic antidepressant,
      climbing behavior composing 75% of the mobile behaviors. The intermediate doses
      of the MAOIs tested, DEP 0.25 mg/kg and MOC 30 mg/kg, decreased immobility and
      increased mobility. The antiimmobility effect of DEP was due to longer climbing
      behavior while MOC enhanced swimming duration. No behavioral changes were seen
      with the administration of the lower and higher doses of the MAOI. Potentiation
      of the antiimmobility effects was observed when ineffective doses of PHEA and of
      DEP or MOC were administered in combination. Differences between the MAO
      inhibitors on the active behaviors were also observed when administered with
      PHEA; DEP and PHEA significantly increased climbing and MOC and PHEA increased
      swimming. This preclinical evaluation of selective MAO inhibitors indicates that
      both MAO-A and MAO-B inhibitors have antidepressant effects. However, to clearly
      demonstrate that these antiimmobility effects are a consequence of increased
      brain concentrations of any one of the several monoamines implicated in the
      mechanism of action of DEP or MOC should be the subject of future studies.

PMID- 9632228
TI  - Behavioral and neural toxicity of arteether in rats.
AB  - Repeated administration of the artemisinin antimalarial compound, 3-arteether
      (AE) (25 mg/kg, i.m.) was evaluated in rats using a two-choice, discrete trial,
      auditory discrimination task and subsequent neurohistology. Rats were trained to
      choose one of two response levers following presentation of white noise or a tone
      + white noise. Increasing and decreasing the intensity of the tone increased and
      decreased discriminability, respectively, and differential reinforcement density
      produced systematic changes in response bias. AE (n = 5) or vehicle (n = 5) was
      injected daily (9-12 days). Initial injections of AE did not affect behavioral
      performance. Continuing daily injections produced significant decreases in choice
      accuracy and significant increases in choice reaction time. When overt signs of
      severe toxicity were observed, rats were sacrificed and significant neural
      pathology was observed in the nucleus trapezoideus of AE-treated rats. In a
      subsequent experiment, AE was injected for 3 (n = 5), 5 (n = 5), or 7 (n = 5),
      consecutive days and performance was examined for an additional 7 days.
      Behavioral disruption was only observed in rats receiving AE for 7 days and the
      greatest degree of disruption occurred after AE injections were completed.
      Histopathological examination showed significant neural pathology in the nuclei
      trapezoideus, superior olive, and ruber of rats receiving 7- and 5-day AE
      regimens, and in the nucleus trapezoideus of rats receiving the 3-day regimen.
      Thus, behavioral disruption reflected, but did not predict, neuropathology. These
      results confirm and extend earlier results demonstrating neurotoxicity of AE in
      rats. Further, these results demonstrate that the auditory discrimination task
      provides an objective behavioral measure of AE neurotoxicity, and thus, can serve
      as a valuable tool for the safety development of AE and other artemisinin
      antimalarial compounds.

PMID- 9632227
TI  - Species differences in regional patterns of 3H-8-OH-DPAT and 3H-zolpidem binding
      in the rat and human brain.
AB  - The rat has proven to be a valuable preclinical model for characterizing effects
      of psychotrophic drugs and for identifying new psychotherapeutic agents in
      pharmacological screens. However, substantial differences have been described
      between the rat and human brain in regard to the neuroanatomical distribution of
      some drug and neurotransmitter receptor binding sites. To assess the utility of
      the rat as a model for the neuroanatomical topography of 5-HT1A and type 1
      benzodiazepine (BDZ) receptors in humans, the distribution of binding sites for
      3H-8-OH-DPAT (5-HT1A agonist) and 3H-zolpidem (type 1 BDZ agonist) was compared
      with autoradiography in select regions of the rat and human brain. Concordance in
      the binding patterns for the two ligands was observed in several brain regions
      for the two species. However, substantial differences were also found in the
      topography of binding sites for the ligands in the rat and human brain. High 3H-8
      OH-DPAT binding was seen in the dorsal raphe nucleus and hippocampal formation in
      both the rat and human brain. However, species differences were observed in the
      relative distribution of ligand binding among hippocampal subregions. In the
      cerebral cortex, the laminar distribution of 3H-8-OH-DPAT binding sites was
      notably different for rats and humans. In humans, outer cortical layers were most
      densely labeled with 3H-8-OH-DPAT, whereas in the rat cortex, the highest binding
      was in the inner layers. A striking difference between rats and humans was
      observed for 3H-8-OH-DPAT binding in the lateral septal nucleus, which was
      densely labeled in the rat but weakly labeled in humans. Substantial differences
      between rats and humans were also observed for 3H-zolpidem binding. In the rat
      brain, high densities of binding sites were found in the medial septum, inferior
      colliculus, and substantia nigra reticulata. These regions showed very low 3H
      zolpidem binding in the human brain. Intermediate binding was seen in the rat
      cerebral cortex, and low binding was found in the hippocampus. By contrast, in
      humans, cerebral cortical regions were the most densely labeled of all regions
      studied, and certain hippocampal subregions exhibited relatively high binding.
      The striking neuroanatomical differences in 3H-8-OH-DPAT and 3H-zolpidem binding
      observed between rats and humans suggest that different functional consequences
      may be produced within specific brain regions after administration of drugs that
      influence 5-HT1A and type 1 BZD receptors.

PMID- 9632229
TI  - Effects of food deprivation on conditioned taste aversions in rats.
AB  - Food deprivation increases the rewarding effects of self-administered drugs such
      as psychomotor stimulants and benzodiazepines. These drugs also possess aversive
      properties and can produce conditioned taste aversions (CTA). Because drug
      seeking behavior is most likely affected by both the rewarding and aversive
      properties of drugs, we hypothesize that food deprivation might also attenuate a
      drug's aversive consequences. The CTAs induced by three different drugs
      (amphetamine, chlordiazepoxide, and LiCl) were assessed separately. Male Long
      Evans rats were assigned to one of two feeding conditions: restricted (maintained
      at 80% of free-feeding body weight), or nonrestricted (with ad lib food). Both
      groups received CTA training, consisting of an intraoral infusion of a novel
      saccharin solution (10 min) followed immediately by one of two i.p. injections:
      paired rats received drug, and unpaired rats received a similar volume of saline.
      After 10 days of ad lib food access, saccharin was presented to all rats again,
      and the latency to reject the tastant was used as an index of CTA learning. The
      rats that had been food restricted at the time of conditioning exhibited
      attenuated CTAs relative to those that had not been deprived. These differences
      were seen only when a rewarding drug (amphetamine or chlordiazepoxide) and not
      when a nonrewarding drug (LiCl) was used as the unconditioned stimulus. In a
      separate experiment, we established that this effect is apparent only when the
      deprivation period precedes conditioning rather than precedes testing. The
      present results indicate that food deprivation modulates the acquisition of a CTA
      induced by amphetamine or chlordiazepoxide, but not LiCl.

PMID- 9632230
TI  - Kappa antinociceptive activity of spiradoline in the cold-water tail-flick assay
      in rats.
AB  - Spiradoline (U62066E) a racemic mixture of the two enantiomers U63639(+) and
      U63640(-), appears to have kappa opioid receptor activity, but the contribution
      of each enantiomer toward this activity is still in question. To determine the
      activity of each enantiomer in comparison to the racemic mixture, the three forms
      were tested in the cold-water tail-flick (CWTF) assay in male Sprague-Dawley
      rats. Antinociception by spiradoline was completely antagonized by naloxone 0.50
      mg/kg, a dose five times that required to antagonize antinociception by fentanyl
      in this same assay. In a second series of tests, fentanyl-induced antinociception
      was markedly reduced, while spiradoline-induced antinociception was essentially
      unchanged. in methadone-tolerant animals. Of the enantiomers, only U63640
      produced antinociception, whereas U63639 failed to affect the nociceptive
      response. Additionally, spiradoline failed to produce antinociception in animals
      pretreated with norbinaltorphimine (kappa receptor specific), but antinociception
      was not affected in animals pretreated with beta-funaltrexamine (mu receptor
      specific). These results show that spiradoline is a full antinociceptive agonist
      in the CWTF assay and that the effects of the drug are mediated through kappa
      opioid receptors.

PMID- 9632231
TI  - Responses of Swiss-Webster mice to repeated plus-maze experience: further
      evidence for a qualitative shift in emotional state?
AB  - Behavioral, endocrinological, and pharmacological data suggest that the emotional
      response of rodents to the elevated plus-maze alters as a function of prior test
      experience. In the present study, 74 intact male Swiss-Webster mice were exposed
      to the plus-maze for 5 min on each of 3 consecutive days, with all test sessions
      recorded on videotape. Behavior patterns for each trial were scored using
      ethological analysis software and the resultant database subjected to a number of
      statistical treatments. Analysis of full session profiles (i.e., 5 min total
      scores) showed that a single prior undrugged experience of the maze increases
      behavioral indices of anxiety and that these alterations are either maintained or
      further enhanced on subsequent trials. Furthermore, the behavioral profile
      evident by trial 3 was largely unchanged when animals were reexposed to the maze
      10 days later. More detailed (i.e., min by min) examination of behavior patterns
      within and between trials demonstrated that unambiguous open arm avoidance is
      acquired by the third minute of trial 1, and that the behavioral profile evident
      by the end of trial 1 is (a) markedly different to that seen at the beginning of
      that trial, and (b) generally maintained or even accentuated on trials 2 and 3.
      The implied impact of prior test experience on future behavioral strategy in the
      maze was strongly supported by a series of factor analyses. Thus, while the
      factor associations of vertical activity and directed exploration remained
      constant across trials, trial 2 and 3 anxiety measures loaded on a separate
      factor to that loading trial 1 anxiety measures. A similar trial 1 vs. trials 2
      and 3 dissociation was observed for measures of locomotor activity. Although the
      present findings are consistent with the proposal that prior test experience
      produces a qualitative shift in emotional response to the elevated plus-maze, the
      precise basis for this change as well as its full significance for our
      understanding of anxiety-related processes remain to be determined.

PMID- 9632232
TI  - Sex differences in escape-avoidance response in mice after acute administration
      of raclopride, clozapine, and SCH 23390.
AB  - Sex differences in the effects of haloperidol in the escape-avoidance response in
      mice have previously been found in various studies carried out in our laboratory.
      Males were more affected than females by the disruptive effects of this
      neuroleptic. The work described herein extended the study of these sex
      differences to raclopride, clozapine, and SCH 23390, using several doses of each
      drug in acute administration. The results showed dose-dependent sex differences
      in the deteriorating effects of these dopamine antagonists in the escape
      avoidance response. Male mice were more affected by the inhibitory effects of
      these drugs, showing fewer escape responses and more nonresponses than females.
      Sex differences were found with all three of the dopamine antagonists studied,
      indicating, therefore, that these differences do not depend on a unique type of
      dopaminergic receptor. The results obtained in motor activity, measured by the
      number of crossings during the adaptation period and the intertrial intervals,
      suggest that the motor effects are not the origin of these differences. It is
      concluded that, besides haloperidol, other dopamine antagonists also show sex
      differences in their behavioral effects in escape-avoidance response in mice,
      with males being more affected than females by the inhibitory action of these
      drugs.

PMID- 9632233
TI  - Dopaminergic parameters during social isolation in low- and high-active mice.
AB  - Alterations induced by social isolation (1 day to 18 weeks) in low- and high
      active mice (LAM and HAM) were studied in respect to locomotor activity, [3H]
      spiperone binding in the striatum, striatal, and cortical dopamine metabolism,
      and presynaptic dopaminergic sensitivity to apomorphine (0.75 mg/kg; i.p.).
      Isolated HAM and LAM showed increased locomotor activity compared to group-housed
      mice after long-term isolation (6-18 weeks). Considering the studied dopaminergic
      parameters, it has been found that social isolation did not affect striatal D2
      receptors, striatal and cortical dopamine metabolism, and apomorphine-mediated
      reduction of dopaminergic metabolism. The change of housing conditions was
      generally associated with an increase of cortical dopamine metabolism after 1
      week. Activity type specific differences in group-housed LAM and HAM were found
      in the basal striatal dopamine metabolism and in the sensitivity of the
      nigrostriatal system to autoreceptor activation. The reduced striatal dopamine
      metabolism and the higher presynaptic sensitivity of HAM may be related to their
      high active running wheel behavior.

PMID- 9632234
TI  - Interactions between N-methyl-D-aspartate receptor antagonists and the
      discriminative stimulus effects of morphine in rats.
AB  - NMDA receptor antagonists have previously been reported to alter some
      pharmacological and behavioral effects of acute and chronic opioid
      administration. The present study assessed the interactions of NMDA antagonists
      with the discriminative stimulus properties of morphine. Adult male Long Evans
      rats were trained to discriminate 3.2 mg/kg of s.c. morphine from water under a
      two-lever fixed-ratio 10 schedule of food reinforcement. During test sessions.
      I.p. injections of the noncompetitive NMDA receptor antagonist dizocilpine (0.03
      0.2 mg/kg), the competitive antagonists NPC 17742 (1-16 mg/kg), and SDZ 220-581
      (0.1-3 mg/kg), the polyamine site antagonist eliprodil (3-17.3 mg/kg), the
      glycine-site partial agonist (+)-HA-966 (3-56 mg/kg), and the nonselective
      glutamate antagonist kynurenic acid (30-150 mg/kg) were coadministered with s.c.
      morphine (1-3.2 mg/kg; interaction tests) or water (generalization tests). In
      generalization tests, none of the compounds completely substituted for morphine.
      Concurrent administration of morphine and NMDA antagonists did not greatly alter
      the discriminative stimulus properties of morphine. Various doses of NPC 17742,
      SDZ 220-581, or (+)-HA-966 somewhat increased levels of morphine-appropriate
      lever selection, whereas some attenuation of morphine-lever selection was
      obtained when morphine was coadministered with eliprodil. These results show that
      NMDA antagonists have minimal interactions with the discriminative stimulus
      effects of morphine.

PMID- 9632235
TI  - Reversal of learned helplessness by morphine in rats: involvement of a dopamine
      mediation.
AB  - The aim of this study was to examine the role of dopamine neurotransmission in
      the effects of morphine in the learned helplessness paradigm in rats, a generally
      recognized model of depression. In this model, rats first exposed to inescapable
      shocks (stressed rats) exhibited an escape deficit in a subsequent shuttle-box
      test performed 48 h later for 3 consecutive days. The numbers of escape failures
      and intertrial crossings (motor activity during each intertrial interval) were
      recorded. Morphine was injected twice daily for 5 days (6 mg/kg/day, s.c.), and
      haloperidol, a preferential D2-dopamine receptor antagonist, was injected i.p. 15
      min before each shuttle-box session. At the highest dose tested (150 microg/kg)
      haloperidol mimicked the behavioral deficit produced by inescapable shocks. A
      37.5 microg/kg dose of haloperidol, which was ineffective by itself, reversed the
      morphine-induced improvement of escape behavior in previously stressed rats and
      the morphine-induced increase in intertrial activity in both stressed and
      nonstressed animals. These results support roles (a) for a dysregulation of
      dopaminergic neuronal activity in the expression of escape deficit subsequent to
      an inescapable aversive situation, and (b) for a dopaminergic mediation in the
      effects of morphine in the learned helplessness paradigm.

PMID- 9632236
TI  - The selective serotonin reuptake inhibitor fluoxetine reduces sexual motivation
      in male rats.
AB  - A male rat put in an open-field arena in which it is free to spend time in the
      vicinity of--but not in contact with--an estrous female, or in the vicinity of a
      male, usually spends more time with the female than with the male or elsewhere.
      Tentatively, the percentage of time spent in the vicinity of the female in this
      paradigm may be regarded as a measure of sexual motivation. In humans, treatment
      with selective serotonin reuptake inhibitors (SSRIs) may cause reduced libido. To
      investigate to what extent serotonin reuptake inhibition influences sexual
      motivation also in rats, we have tested the effect of subchronic treatment with
      fluoxetine on the behavior in the sexual motivation test described above; in
      addition, the effect of fluoxetine on male copulatory behavior was studied.
      Fluoxetine significantly reduced sexual motivation at subchronic but not at acute
      administration; moreover, fluoxetine-treated rats displayed an increased
      ejaculation latency. It is concluded that humans and rats respond similarly to
      the SSRI fluoxetine with respect to various aspects of sexual behavior.

PMID- 9632237
TI  - Social interactions, brain monoamines, and GABA alterations in MFB-lesioned cats.
AB  - The effects of denervation of central noradrenergic system on the interpartner
      relationships of adult cats were examined in a predatory test in the competitive
      situation for paired animals. Direct administration of the noradrenaline
      neurotoxin, N-2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP-4 12 microg) into the
      medial forebrain bundle (MFB) of submissive cats changed previously established
      dominant-submissive relationship. Biochemical analysis demonstrated a significant
      reduction of noradrenaline (NA) concentration in the hypothalamus (AH), amygdala
      (AM), hippocampus (HC), and frontal cortex (CTX), and elevation of NA content in
      the midbrain central gray matter (CG) in MFB-lesioned cats. Simultaneously, DSP-4
      induced lesions exerted significant decrease of 3-methoxy-4-hydroxyphenylethylene
      glycol (MHPG) content in AH, CG, HC and CTX, and increased GABA level in AH, CG,
      AM, and HC. These results suggest that a coincident decrease of NA metabolism and
      increase of GABA metabolism led to fear drive reduction.

PMID- 9632238
TI  - Acute and chronic fluoxetine treatment decreases the sensitivity of rats to
      rewarding brain stimulation.
AB  - The effects of fluoxetine on rewarding brain stimulation were determined in eight
      Wistar rats using a rate-independent discrete-trial threshold measure. Rats were
      implanted with bipolar, stainless steel electrodes either into the ventral
      tegmental area (VTA) or medial forebrain bundle (MFB). Acute administration of
      fluoxetine significantly raised the reward threshold (decreased sensitivity) at
      doses of 2.5, 5.0, 10.0, and 20.0 mg/kg, i.p., without altering latency of
      response. There were no significant differences between VTA and MFB groups. To
      determine the effects of chronic treatment, daily injections of 5.0 mg/kg
      fluoxetine were administered to rats for 21 days. Chronic treatment of fluoxetine
      continued to significantly elevate reward thresholds with no evidence of
      tolerance. The results of these experiments suggest that fluoxetine does not
      possess abuse potential and that serotonin produces an inhibitory effect on the
      mesolimbic dopaminergic reward system. Furthermore, these results suggest that
      the antidepressant effects of fluoxetine are not the direct result of excitation
      of brain reward systems, at least in the same manner as abused substances, for
      example, cocaine.

PMID- 9632239
TI  - Lead, attention, and impulsive behavior: changes in a fixed-ratio waiting-for
      reward paradigm.
AB  - Similar to the effects observed in children diagnosed with attention deficit
      hyperactivity disorder (ADHD), experimental animals exposed to lead (Pb) exhibit
      behaviors attributed to "impulsivity" and "inability to inhibit inappropriate
      responding." Such behaviors have led some to suggest that Pb exposure is
      associated with attention deficit. Based on the hypothesis that attention
      deficits are related to an ineffectiveness of delayed reinforcement, this study
      examined the effects of chronic postweaning Pb exposure on an FR waiting-for
      reward paradigm. Rats were exposed chronically from weaning to 0, 50, or 150 ppm
      Pb acetate in water and following 40 days of exposure, trained on a fixed-ratio
      (FR) wait behavioral baseline. A total of 50 lever press responses (FR 50)
      produced food delivery. After earning an FR pellet, "free" pellets could be
      obtained by waiting; emission of another lever press reinitiated the FR
      requirement. "Free" pellets were delivered at increasing intervals (2 s, 4 s, 6
      s, etc.). Pb exposure increased response rates on the FR schedule and decreased
      the mean longest waiting time, but also resulted in a higher number of responses
      per reinforcer than exhibited by controls. These Pb-induced differences are
      consistent with an inability to manage delays of reinforcement.

PMID- 9632240
TI  - The delayed effects of phencyclidine (PCP) disrupt latent inhibition in a
      conditioned taste aversion paradigm.
AB  - The acute effects of a low dose of phencyclidine (PCP) and the delayed effects of
      a high dose of PCP on latent inhibition (LI) were assessed in a series of
      experiments using conditioned taste aversion paradigms. Each paradigm involved a
      preexposure phase in which water-deprived male rats were allowed access to either
      water (nonpreexposed; NPE) or 5% sucrose (preexposed; PE), followed by a
      conditioning phase in which animals were allowed access to sucrose and
      subsequently injected with the negative reinforcer lithium chloride, and a test
      phase in which animals were allowed access to both sucrose and water. LI was
      assessed by comparing the %-sucrose consumed in PE and NPE groups on the test
      day. The effects of low-dose PCP (2.5 mg/kg) were assessed by comparing LI in
      animals treated with vehicle or PCP 15 min prior to the onset of the preexposure
      and conditioning phases. A 4-day paradigm involved 2 days of preexposure followed
      by a day of conditioning and a test day. This paradigm produced comparable levels
      of LI in vehicle and PCP-treated animals. A 5-day extinction paradigm involved 2
      days of preexposure followed by 2 days of conditioning and a test day. This
      paradigm abolished LI in vehicle and PCP-treated animals. A 3-day paradigm
      involved 1 day of preexposure followed by a day of conditioning and a test day.
      One day of preexposure induced a modified LI effect in both in vehicle and PCP
      treated animals. The delayed effects of high dose PCP (8.6 mg/kg) were assessed
      by comparing LI in animals treated with vehicle or PCP 20 h prior to the onset of
      the preexposure and conditioning phases in the 4-day paradigm. PCP disrupted
      latent inhibition in this paradigm. The results are discussed in the context of
      their relevance to the ability for PCP to model schizophrenic symptomatology.

PMID- 9632241
TI  - The enhancement of morphine antinociception in mice by delta9
      tetrahydrocannabinol.
AB  - We have previously reported that intracerebroventricular or intrathecal
      administration of inactive doses of delta9-tetrahydrocannabinol (THC) greatly
      enhance the antinociceptive potency of morphine in the mouse tail-flick test.
      Experiments were conducted to test the hypothesis that morphine's potency would
      be enhanced in mice receiving THC and morphine by conventional per os (p.o.) and
      subcutaneously (s.c.) routes of administration. Antinociception was measured in
      the tail-flick test of radiant heat after administration of different
      combinations of THC and morphine p.o. and s.c. Subcutaneous administration of THC
      (4 and 25 mg/kg) increased the potency of s.c. morphine 8.5- and 22.3-fold,
      respectively, while s.c. THC (25 mg/kg) increased the potency of p.o. morphine
      3.1-fold. Per os administration of THC (10 and 20 mg/kg) increased the potency of
      s.c. and p.o. morphine 11.4-fold and 7.6-fold, respectively. Thus, morphine's
      potency was significantly increased regardless of the enteral and parenteral
      routes of THC and morphine administration. The synthetic receptor selective
      cannabinoid CP-55, 940 (0.1 mg/kg, s.c.) also enhanced morphine's potency.
      Finally, the ability of the CB1 receptor antagonist SR141716A to antagonize the
      enhancement of morphine by THC indicates that THC was acting through a
      cannabinoid receptor mechanism.

PMID- 9632242
TI  - Reinforcing effects of nicotinic compounds: intravenous self-administration in
      drug-naive mice.
AB  - The nicotinic compounds (-)-cytisine, (-)-lobeline, (+/-)-epibatidine, (S)
      3methyl-5-(1-methyl-2-pyrrolidinyl)isoaxzole (ABT-418), (-)-nicotine, and cocaine
      were compared in an acute self-administration model using drug-naive mice that
      could self-administer intravenous infusions contingent on nose poking (fixed
      ratio 1 with no time out). Although the nose pokes of yoked control mice were
      unaffected by unit dose, inverted U-shaped unit dose response curves were seen
      with cocaine (up to 0.26 mg/kg/infusion), nicotine (up to 0.175 mg/kg/infusion),
      cytisine (up to 0.125 mg/kg/infusion), and lobeline (up to 1.25 mg/kg/infusion)
      in mice receiving infusions contingent upon nose poke responses. Epibatidine (up
      to 1.25 microg/kg/infusion) and ABT-418 (up to 0.125 mg/kg/infusion) failed to
      exhibit inverted U-shaped unit dose response curves. The present studies
      demonstrate that cytisine and lobeline, but not ABT-418 or epibatidine, were self
      administered by drug-naive mice in a manner similar to cocaine and nicotine.
      These findings are discussed in terms of potency and selectivity at the
      alpha4beta2 nicotinic acetylcholine receptor subunit combination.

PMID- 9632243
TI  - Social learning of a food preference in male and female Mongolian gerbils is
      facilitated by the anxiolytic, chlordiazepoxide.
AB  - Social transmission of a food preference in Mongolian gerbils (Meriones
      unguiculatus) depends on the presence of a social bond between the interacting
      animals. An "observer" gerbil can acquire a preference for a novel food item from
      a familiar and, or related "demonstrator" animal. However, exposure to an
      unfamiliar and unrelated demonstrator gerbil does not lead to acquisition of a
      food preference, even though the extent of social interaction and likelihood of
      transmission of food information is unaffected. Likewise, individual preexposure
      to a novel food does not affect diet preference in individual animals. Here we
      show that oral, nongavage, administration of the benzodiazepine anxiolytic,
      chlordiazcpoxide (CDP, 2.5, 5, and 10 mg/kg) has significant dose-associated
      differential facilitatory effects on social learning in male and female gerbils,
      while having no significant effects on either individual learning or total food
      consumption. These results suggest that the CDP mediated reduction of the anxiety
      associated with the interactions between unfamiliar/unrelated gerbils facilitates
      social learning. These findings also rise the possibility of sex differences in
      socially related anxiety and the effects of CDP on social learning in gerbils.

PMID- 9632244
TI  - Sexual behavior in male rats after radiofrequency or dopamine-depleting lesions
      in nucleus accumbens.
AB  - Considerable neurochemical evidence links dopamine (DA) in nucleus accumbens
      (NAcc) to male sexual behavior. The present experiments were conducted to extend
      this information to the male's sexual response to remote stimuli from estrous
      female (noncontact erection; NCE). Male rats were tested for copulation and NCE
      after either 6-hydroxydopamine (6-OHDA) or radiofrequency (RF) lesions in NAcc).
      Males with an average 78% depletion of DA in NAcc had a lower incidence of NCE,
      longer latency to display NCE, and fewer erections. DA-depleted males also had
      less locomotor activity after injections of d-amphetamine, and reductions in
      apomorphine-induced yawning, but a normal incidence of penile erection. Males
      with RF lesions of the NAcc had longer NCE latencies. All males copulated to
      ejaculation after either 6-OHDA or RF lesions with little or no deficit, although
      the 6-OHDA-treated males had longer intromission latencies. The NCE deficit
      supports the hypothesized role of NAcc DA in arousal processes in responding to
      remote cues from estrous females. The minimal effect of lesions on copulation
      suggests that the presence of additional proximal stimulation during copulation
      may overcome the deficits induced by DA depletions or lesions in NAcc.

PMID- 9632245
TI  - Effects of "binge" pattern cocaine on stereotypy and locomotor activity in
      C57BL/6J and 129/J mice.
AB  - This study characterized the behavioral response to cocaine in two strains of
      mice, the C57BL/6J and 129/J strains, commonly utilized as host strains for
      transgenic and "knockout" mice. The psychomotor stimulating effects of four doses
      of cocaine (2.5, 5.0, 10.0, and 15.0 mg/kg/injection) with a saline control,
      administered in a "binge" pattern (three equal injections at hourly intervals)
      for 3 days were examined in adult male C57BL/6J and 129/J mice. Behavioral
      stereotypy in the home cage, was rated 15, 30, and 45 min following each
      injection. Spontaneous locomotor activity in the home cage was also monitored.
      Cocaine, at doses of 10.0 or 15.0 mg/kg, produced behavioral stereotypy in both
      C57BL/6J mice (p < 0.0001) and 129/J mice (p < 0.0001), whereas lower doses did
      not. The magnitude of stereotypy was significantly lower in 129/J mice than in
      C57BL/6J mice receiving identical doses of cocaine. C57BL/6J mice also
      demonstrated a dose-dependent cocaine-induced stimulation of locomotor activity
      following administration of 10.0 or 15.0 mg/kg of cocaine (p < 0.0005). In
      contrast, 129/J mice did not exhibit increased locomotion in response to any dose
      of cocaine tested. These results demonstrate that strain differences in drug
      induced behavior may be more pronounced in one measure (i.e., locomotor activity)
      than in another (i.e., stereotypy) and indicate the importance of multiple
      behavioral measures.

PMID- 9632246
TI  - Metal ion homeostasis and intracellular parasitism.
AB  - Bacteria possess multiple mechanisms for the transport of metal ions. While many
      of these systems may have evolved in the first instance to resist the detrimental
      effects of toxic environmental heavy metals, they have since become adapted to a
      variety of important homeostatic functions. The 'P'-type ATPases play a key role
      in metal ion transport in bacteria. A Cu+-ATPase from the intracellular bacterium
      Listeria monocytogenes is implicated in pathogenesis, and similar pumps in
      Mycobacterium tuberculosis and M. leprae may play a comparable role.
      Intracellular bacteria require transition metal cations for the synthesis of
      superoxide dismutases and catalases, which constitute an important line of
      defence against macrophage-killing mechanisms. The macrophage protein Nramp1,
      which confers resistance to a variety of intracellular pathogens, has also been
      shown recently to be a divalent amphoteric cation transporter. Mycobacterial
      homologues have recently been identified by genomic analysis. These findings
      suggest a model in which competition for divalent cations plays a pivotal role in
      the interaction between host and parasite.

PMID- 9632247
TI  - Genetic advances for studying Mycobacterium tuberculosis pathogenicity.
AB  - Tuberculosis remains the greatest cause of death worldwide because of a single
      pathogen. Despite its importance, the genetic basis of the pathogenicity of
      Mycobacterium tuberculosis remains poorly understood, mainly because the most
      productive investigative approach, molecular genetic analysis, has been severely
      hampered by a lack of efficient tools. However, significant advances, including
      the development of methods for inactivating genes and studying their expression
      with reporter genes, have been recently made. This progress may lead to
      opportunities for developing new vaccines and antituberculous drugs. The aim of
      this review is to examine the present state of the art in mycobacterial molecular
      genetics and pinpoint some expected or promising areas for future research.

PMID- 9632248
TI  - Ordered expression of ftsQA and ftsZ during the Caulobacter crescentus cell
      cycle.
AB  - The mechanisms by which bacterial cell division and DNA replication are co
      ordinated are still unknown. We have used the easily synchronizable bacterium
      Caulobacter crescentus to determine when the cell division genes ftsQ and ftsA
      are transcribed during the DNA replication cycle and to compare their
      transcription with that of ftsZ. Unlike the situation in Escherichia coli,
      transcription of ftsQ and ftsA does not extend into ftsZ in Caulobacter. ftsQ and
      ftsA are co-transcribed by a strong promoter, P(QA), present within the end of
      the ddl gene upstream of ftsQ. Transcription of P(QA) is turned on at the end of
      the DNA replication period, coincident with the end of the ftsZ transcription
      period. ftsA is also transcribed by another promoter, P(A), present between ftsQ
      and ftsA. P(A) transcription is approximately 10 times weaker than P(QA) and
      occurs during the DNA replication period. Transcription of ftsA by P(A) is
      sufficient for cell viability, but is not sufficient for normal cell division.
      When the transcription of ftsA is increased constitutively, cell division is
      inhibited and stalks are synthesized at aberrant positions. Thus, transcription
      of ftsA and ftsZ mimics their order of action in Caulobacter and proper
      transcription of ftsA has to be maintained for normal cell division and
      differentiation.

PMID- 9632249
TI  - NarJ is a specific chaperone required for molybdenum cofactor assembly in nitrate
      reductase A of Escherichia coli.
AB  - The formation of active membrane-bound nitrate reductase A in Escherichia coli
      requires the presence of three subunits, NarG, NarH and NarI, as well as a fourth
      protein, NarJ, that is not part of the active nitrate reductase. In narJ strains,
      both NarG and NarH subunits are associated in an unstable and inactive NarGH
      complex. A significant activation of this complex was observed in vitro after
      adding purified NarJ-6His polypeptide to the cell supernatant of a narJ strain.
      Once the apo-enzyme NarGHI of a narJ mutant has become anchored to the membrane
      via the NarI subunit, it cannot be reactivated by NarJ in vitro. NarJ protein
      specifically recognizes the catalytic NarG subunit. Fluorescence, electron
      paramagnetic resonance (EPR) spectroscopy and molybdenum quantification based on
      inductively coupled plasma emission spectroscopy (ICPES) clearly indicate that,
      in the absence of NarJ, no molybdenum cofactor is present in the NarGH complex.
      We propose that NarJ is a specific chaperone that binds to NarG and may thus keep
      it in an appropriate competent-open conformation for the molybdenum cofactor
      insertion to occur, resulting in a catalytically active enzyme. Upon insertion of
      the molybdenum cofactor into the apo-nitrate reductase, NarJ is then dissociated
      from the activated enzyme.

PMID- 9632250
TI  - Initiation of biofilm formation in Pseudomonas fluorescens WCS365 proceeds via
      multiple, convergent signalling pathways: a genetic analysis.
AB  - Populations of surface-attached microorganisms comprising either single or
      multiple species are commonly referred to as biofilms. Using a simple assay for
      the initiation of biofilm formation (e.g. attachment to an abiotic surface) by
      Pseudomonas fluorescens strain WCS365, we have shown that: (i) P. fluorescens can
      form biofilms on an abiotic surface when grown on a range of nutrients; (ii)
      protein synthesis is required for the early events of biofilm formation; (iii)
      one (or more) extracytoplasmic protein plays a role in interactions with an
      abiotic surface; (iv) the osmolarity of the medium affects the ability of the
      cell to form biofilms. We have isolated transposon mutants defective for the
      initiation of biofilm formation, which we term surface attachment defective
      (sad). Molecular analysis of the sad mutants revealed that the ClpP protein (a
      component of the cytoplasmic Clp protease) participates in biofilm formation in
      this organism. Our genetic analyses suggest that biofilm formation can proceed
      via multiple, convergent signalling pathways, which are regulated by various
      environmental signals. Finally, of the 24 sad mutants analysed in this study,
      only three had defects in genes of known function. This result suggests that our
      screen is uncovering novel aspects of bacterial physiology.

PMID- 9632251
TI  - EspE, a novel secreted protein of attaching and effacing bacteria, is directly
      translocated into infected host cells, where it appears as a tyrosine
      phosphorylated 90 kDa protein.
AB  - Shiga toxin-producing Escherichia coli (STEC), enteropathogenic E. coli (EPEC)
      and some strains of Hafnia alvei are capable of inducing attaching and effacing
      (A/E) lesions, characterized by tight apposition of the bacteria to the
      eukaryotic membrane and formation of actin-based pedestals. In this study, we
      report on the identification of EspE, a novel secreted 80 kDa protein of A/E
      bacteria. During infection, EspE is delivered into the cytoplasm of the infected
      host cell, where it is detected as a higher-molecular-weight form of 90 kDa. We
      present evidence that translocated EspE becomes tyrosine phosphorylated and that
      this modified form of EspE may be identical to Hp90, the putative receptor of
      EPEC intimin. Bacteria of the classic enterohaemorrhagic E. coli (EHEC) serotype
      O157:H7 fail to induce a tyrosine phosphorylation of EspE and differ in this
      respect from other A/E bacteria. Translocated EspE, whether tyrosine
      phosphorylated or not, becomes incorporated into the bacteria-induced
      cytoskeletal structures, where it normally colocalizes with filamentous actin.
      EPEC are also able to induce 'pseudopods', elongated pedestals that have recently
      been implicated in a novel kind of actin-based motility. EspE is enriched at the
      tip of these structures, suggesting its involvement in the process of actin
      dynamics, which is triggered during the attaching and effacing process.

PMID- 9632252
TI  - An RpoS (sigmaS) homologue regulates acylhomoserine lactone-dependent
      autoinduction in Ralstonia solanacearum.
AB  - Many bacteria sense an appropriate growth condition or a critical population
      density for gene expression by producing acylhomoserine lactones (acyl-HSLs) that
      act as intercellular autoinduction signals. We recently showed that, in Ralstonia
      (Pseudomonas) solanacearum, a phytopathogenic bacterium, acyl-HSL production
      requires soll, which encodes a putative acyl-HSL synthase, and that its
      expression is positively regulated by the acyl-HSL-responsive SolR
      transcriptional regulator. This acyl-HSL-dependent autoinduction system is
      noteworthy because (i) it is regulated by a 'higher level' autoinducer system
      (responsive to 3-hydroxypalmitic acid methyl ester) via PhcA, a LysR-type
      transcriptional regulator and (ii) acyl-HSL production requires two additional
      unlinked loci. As reported here, cloning and sequencing of one of these other
      loci revealed that it encodes a homologue of RpoS, an alternative sigma factor
      (sigmaS) that in other bacteria activates gene expression during stationary phase
      or in response to stress conditions. R. solanacearum RpoS (RpoS(Rso)) was
      demonstrated to function as a sigma factor because when introduced in trans into
      an Escherichia coli rpoS mutant it largely restored expression of the RpoS
      dependent bolAp1 gene. Mutation of rpoS(Rso) in R. solanacearum reduced survival
      during starvation and low pH conditions, but did not affect survival during
      exposure to hydrogen peroxide, high osmolarity or high temperature. This mutant
      was also altered in its production of several virulence factors and wilted tomato
      plants several days more slowly than the wild-type parent. Transcription of solR
      and soll were decreased in an rpoS(Rso) background (thereby reducing acyl-HSL
      production), but neither mutations in solR, soll or phcA nor addition of acyl
      HSLs affected rpoS(Rso) expression. Therefore, in R. solanacearum the acyl-HSL
      dependent autoinduction system is controlled both by a second autoinduction
      system and by the RpoS(Rso) sigma factor.

PMID- 9632253
TI  - Isolation and characterization of Fap1, a fimbriae-associated adhesin of
      Streptococcus parasanguis FW213.
AB  - An adhesin of Streptococcus parasanguis FW213, a primary colonizer of the tooth
      surface, has been purified from the culture medium by immunoaffinity
      chromatography. The purified protein has a molecular mass of 200 kDa and stains
      positively for carbohydrate. The amino-terminal sequence indicated that this
      protein represented a unique streptococcal surface protein. Immunogold labelling
      of the bacterium indicated that this protein was associated with fimbriae and
      designated Fap1 (fimbriae-associated protein). A polymerase chain reaction (PCR)
      product based on the amino terminus of Fap1 was used to probe an FW213 genomic
      library. A 9 kb fragment containing the fap1 gene was isolated and 2.5 kb have
      been sequenced. Generation of fap1 mutants by a single cross-over (Campbell
      insertion) or a non-polar allelic exchange abolished the expression of Fap1. The
      inactivation of fap1 resulted in a dramatic reduction in the expression of the
      long peritrichous fimbriae and adhesion to saliva-coated hydroxylapatite (SHA).
      Northern blots probed with an internal gene fragment of fap1 hybridized to a 9 kb
      transcript, which suggests that fap1 is transcribed as a polycistronic message.
      These data demonstrate that Fap1 is a unique streptococcal adhesin that is
      involved in the assembly of S. parasanguis FW213 fimbriae and adhesion to SHA.

PMID- 9632254
TI  - Distinct roles of an alternative sigma factor during both free-swimming and
      colonizing phases of the Vibrio cholerae pathogenic cycle.
AB  - Vibrio cholerae, the bacterium that causes cholera, has a pathogenic cycle
      consisting of a free-swimming phase outside its host, and a sessile virulent
      phase when colonizing the human small intestine. We have cloned the V. cholerae
      homologue of the rpoN gene (encoding sigma54) and determined its role in the
      cholera pathogenic cycle by constructing an rpoN null mutant. The V. cholerae
      rpoN mutant is non-motile; examination of this mutant by electron microscopy
      revealed that it lacks a flagellum. In addition to flagellar synthesis, sigma54
      is involved in glutamine synthetase expression. Moreover, the rpoN mutant is
      defective for colonization in an infant mouse model of cholera. We present
      evidence that the colonization defect is distinct from the non-motile and Gln
      phenotypes of the rpoN mutant, implicating multiple and distinct roles of sigma54
      during the V. cholerae pathogenic cycle. RNA polymerase containing sigma54
      (sigma54-holoenzyme) has an absolute requirement for an activator protein to
      initiate transcription. We have identified three regulatory genes, flrABC
      (flagellar regulatory proteins ABC) that are additionally required for flagellar
      synthesis. The flrA and flrC gene products are sigma54-activators and form a
      flagellar transcription cascade. flrA and flrC mutants are also defective for
      colonization; this phenotype is probably independent of non-motility. An flrC
      constitutive mutation (M114-->I) was isolated that is independent of its cognate
      kinase FlrB. Expression of the constitutive FlrCM114-->I from the cholera toxin
      promoter resulted in a change in cell morphology, implicating involvement of FlrC
      in cell division. Thus, sigma54 holoenzyme, FlrA and FlrC transcribe genes for
      flagellar synthesis and possibly cell division during the free-swimming phase of
      the V. cholerae life cycle, and some as yet unidentified gene(s) that aid
      colonization within the host.

PMID- 9632256
TI  - Distal genes of the nuo operon of Rhodobacter capsulatus equivalent to the
      mitochondrial ND subunits are all essential for the biogenesis of the respiratory
      NADH-ubiquinone oxidoreductase.
AB  - Seven out of the 13 proteins encoded by the mitochondrial genome of mammals
      (peptides ND1 to ND6 plus ND4L) are subunits of the respiratory NADH-ubiquinone
      oxidoreductase (complex I). The function of these ND subunits is still poorly
      understood. We have used the NADH-ubiquinone oxidoreductase of Rhodobacter
      capsulatus as a model for the study of the function of these proteins. In this
      bacterium, the 14 genes encoding the NADH-ubiquinone oxidoreductase are clustered
      in the nuo operon. We report here on the biochemical and spectroscopic
      characterization of mutants individually disrupted in five nuo genes, equivalent
      to mitochondrial genes nd1, nd2, nd5, nd6 and nd4L. Disruption of any of these
      genes in R. capsulatus leads to the suppression of NADH dehydrogenase activity at
      the level of the bacterial membranes and to the disappearance of complex I
      associated iron-sulphur clusters. Individual NUO subunits can still be
      immunodetected in the membranes of these mutants, but they do not form a
      functional subcomplex. In contrast to these observations, disruption of two ORFs
      (orf6 and orf7), also present in the distal part of the nuo operon, does not
      suppress NADH dehydrogenase activity or complex I-associated EPR signals, thus
      demonstrating that these ORFs are not essential for the biosynthesis of complex
      I.

PMID- 9632255
TI  - The ArcA/ArcB two-component regulatory system of Escherichia coli is essential
      for Xer site-specific recombination at psi.
AB  - Two recombinases, XerC and XerD, act at the recombination sites psi and cer in
      plasmids pSC101 and Co1E1 respectively. Recombination at these sites maintains
      the plasmids in a monomeric state and helps to promote stable plasmid
      inheritance. The accessory protein PepA acts at both psi and cer to ensure that
      only intramolecular recombination takes place. An additional accessory protein,
      ArgR, is required for recombination at cer but not at psi. Here, we demonstrate
      that the ArcA/ArcB two-component regulatory system of Escherichia coli, which
      mediates adaptation to anaerobic growth conditions, is required for efficient
      recombination in vivo at psi. Phosphorylated ArcA binds to psi in vitro and
      increases the efficiency of recombination at this site. Binding of ArcA to psi
      may contribute to the formation of a higher order synaptic complex between a pair
      of psi sites, thus helping to ensure that recombination is intramolecular.

PMID- 9632257
TI  - The expression of the secreted aspartyl proteinases Sap4 to Sap6 from Candida
      albicans in murine macrophages.
AB  - Medically important yeasts of the genus Candida secrete aspartyl proteinases
      (Sap), which are of particular interest as virulence factors. Six closely related
      gene sequences, SAP1 to SAP6, for secreted proteinases are present in Candida
      albicans. The methylotrophic yeast Pichia pastoris was chosen as an expression
      system for preparing substantial amounts of each Sap isoenzyme. Interestingly,
      Sap4, Sap5 and Sap6, which have not yet been detected in C. albicans cultures in
      vitro, were produced as active recombinant enzymes. Different Sap polyclonal
      antibodies were raised in rabbits and tested before further application by enzyme
      linked immunosorbent assay (ELISA) against each recombinant Sap. Two antisera
      recognized only Sap4 to Sap6. Using these antisera, together with sap null
      mutants obtained by targeted mutagenesis, we could demonstrate a high production
      of Sap4, Sap5 and Sap6 by C. albicans cells after phagocytosis by murine
      peritoneal macrophages. Furthermore, a delta sap4,5,6 null mutant was killed 53%
      more effectively after contact with macrophages than the wild-type strain. These
      results support a role for Sap4 to Sap6 in pathogenicity.

PMID- 9632258
TI  - The psychrotrophic bacterium Yersinia enterocolitica requires expression of pnp,
      the gene for polynucleotide phosphorylase, for growth at low temperature (5
      degrees C).
AB  - The psychrotrophic bacterium Yersinia enterocolitica is characterized by
      temperature-dependent adaptations. To investigate Y. enterocolitica genes
      involved in cold adaptation, a mutant restricted in its ability to grow at 5
      degrees C was isolated from a transposon mutant library. The transposon insertion
      site in this psychrotrophy-defective (PD) mutant mapped 16 bp upstream of an open
      reading frame whose predicted amino acid sequence showed 93% similarity with the
      Escherichia coli exoribonuclease polynucleotide phosphorylase (PNPase), encoded
      by pnp. Expression of this gene was blocked in the PD mutant. However, the
      introduction of a second copy of pnp, including 0.33 kbp sequences upstream of
      its coding region, into the chromosome of the PD mutant restored pnp expression
      as well as the ability to grow at 5 degrees C. Furthermore, the expression of pnp
      appeared to be temperature dependent: in the parental Y. enterocolitica strain,
      the levels of both pnp mRNA and PNPase were 1.6-fold higher at 5 degrees C
      compared with 30 degrees C. A similarly enhanced level of PNPase at 5 degrees C
      was observed in the merodiploid recombinant strain, which indicates that the 0.33
      kbp region upstream of pnp harboured a cold-inducible promoter. A putative cold
      shock promoter motif (ATTGG) was observed in this region.

PMID- 9632259
TI  - Conjugal transfer of chromosomal DNA in Mycobacterium smegmatis.
AB  - The genus Mycobacterium includes the major human pathogens Mycobacterium
      tuberculosis and Mycobacterium leprae. The development of rational drug
      treatments for the diseases caused by these and other mycobacteria requires the
      establishment of basic molecular techniques to determine the genetic basis of
      pathogenesis and drug resistance. To date, the ability to manipulate and move DNA
      between mycobacterial strains has relied on the processes of transformation and
      transduction. Here, we describe a naturally occurring conjugation system present
      in Mycobacterium smegmatis, which we anticipate will further facilitate the
      ability to manipulate the mycobacterial genome. Our data rule out transduction
      and transformation as possible mechanisms of gene transfer in this system and are
      most consistent with conjugal transfer. We show that recombinants are not the
      result of cell fusion and that transfer occurs from a distinct donor to a
      recipient. One of the donor strains is mc(2)155, a highly transformable
      derivative that is considered the prototype laboratory strain for mycobacterial
      genetics; the demonstration that it is conjugative should increase its genetic
      manipulability dramatically. During conjugation, extensive regions of chromosomal
      DNA are transferred into the recipient and then integrated into the recipient
      chromosome by multiple recombination events. We propose that DNA transfer is
      occurring by a mechanism similar to Hfr conjugation in Escherichia coli.

PMID- 9632260
TI  - Functional and structural conservation in the mechanosensitive channel MscL
      implicates elements crucial for mechanosensation.
AB  - mscL encodes a channel in Escherichia coli that is opened by membrane stretch
      force, probably serving as an osmotic gauge. Sequences more or less similar to
      mscL are found in other bacteria, but the degree of conserved function has been
      unclear. We subcloned and expressed these putative homologues in E. coli and
      examined their products under patch clamp. Here, we show that each indeed encodes
      a conserved mechanosensitive channel activity, consistent with the interpretation
      that this is an important and primary function of the protein in a wide range of
      bacteria. Although similar, channels of different bacteria differ in kinetics and
      their degree of mechanosensitivity. Comparison of the primary sequence of these
      proteins reveals two highly conserved regions, corresponding to domains
      previously shown to be important for the function of the wild-type E. coli
      channel, and a C-terminal region that is not conserved in all species. This
      structural conservation is providing insight into regions of this molecule that
      are vital to its role as a mechanosensitive channel and may have broader
      implications for the understanding of other mechanosensitive systems.

PMID- 9632261
TI  - Targeting of Yersinia Yop proteins into the cytosol of HeLa cells: one-step
      translocation of YopE across bacterial and eukaryotic membranes is dependent on
      SycE chaperone.
AB  - Pathogenic Yersiniae adhere to and kill macrophages by targeting some of their
      Yop proteins into the eukaryotic cytosol. There is debate about whether YopE
      targeting proceeds as a direct translocation of polypeptide between cells or in
      two distinct steps, each requiring specific signals for YopE secretion across the
      bacterial envelope and for translocation into the eukaryotic cytosol. Here, we
      used the selective solubilization of the eukaryotic plasma membrane with
      digitonin to measure Yop targeting during Yersinia infections of HeLa cells.
      YopE, YopH, YopM and YopN were found in the eukaryotic cytosol but not in the
      extracellular medium. When bound to SycE chaperone in the Yersinia cytoplasm,
      YopE residues 1-100 are necessary and sufficient for the targeting of hybrid
      neomycin phosphotransferase. Electron microscopic analysis failed to detect an
      extracellular intermediate of YopE targeting, suggesting a one-step translocation
      mechanism.

PMID- 9632262
TI  - The control of Azorhizobium caulinodans nifA expression by oxygen, ammonia and by
      the HF-I-like protein, NrfA.
AB  - The control of Azorhizobium caulinodans nifA expression in response to oxygen and
      ammonia involves FixLJ, FixK, NtrBC, NtrXY and the HF-I-like protein NrfA. The
      regulation is thus complex and possibly involves post-transcriptional regulation
      by NrfA. The coding region of nifA was determined using a translational lacZ
      fusion and by site-directed mutagenesis to identify which of four in frame AUG
      codons was used. The major NifA protein is translated from the second AUG codon
      and is predicted to consist of 613 amino acids. Primer extension analysis showed
      a major transcript starting 34 bp downstream from the anaerobox in wild-type,
      nifA, rpoN, ntrC and nrfA strains, but not in a fixK mutant. FixK- and oxygen
      dependent transcription of nifA was confirmed by the analysis of four
      transcriptional nifA-lacZ fusions with fusion junctions at positions +1, +47,
      +110 and +181 with respect to the start site. Regulation by ammonia was
      independent of FixK and RpoN, NtrC being only partially required. Thus, there may
      be another type of nitrogen control that does not involve NtrC in A. caulinodans.
      NrfA is not required for the initiation of nifA transcription but, most probably,
      has an effect on nifA mRNA stability and/or translation. NrfA also restores the
      defect in rpoS translation to an Escherichia coli hfq mutant, indicating that HF
      I and NrfA have similar activities in both A. caulinodans and E. coli.

PMID- 9632263
TI  - Biochemical and genetic characterization of benzylsuccinate synthase from Thauera
      aromatica: a new glycyl radical enzyme catalysing the first step in anaerobic
      toluene metabolism.
AB  - Toluene is anoxically degraded to CO2 by the denitrifying bacterium Thauera
      aromatica. The initial reaction in this pathway is the addition of fumarate to
      the methyl group of toluene, yielding benzylsuccinate as the first intermediate.
      We purified the enzyme catalysing this reaction, benzylsuccinate synthase (EC
      4.1.99-), and studied its properties. The enzyme was highly oxygen sensitive and
      contained a redox-active flavin cofactor, but no iron centres. The native
      molecular mass was 220 kDa; four subunits of 94 (alpha), 90 (alpha'), 12 (beta)
      and 10 kDa (gamma) were detected on sodium dodecyl sulphate (SDS) gels. The N
      terminal sequences of the alpha- and alpha'-subunits were identical, suggesting a
      C-terminal degradation of half of the alpha-subunits to give the alpha'-subunit.
      The composition of native enzyme therefore appears to be alpha2beta2gamma2. A 5
      kb segment of DNA containing the genes for the three subunits of benzylsuccinate
      synthase was cloned and sequenced. The masses of the predicted gene products
      correlated exactly with those of the subunits, as determined by electrospray mass
      spectrometry. Analysis of the derived amino acid sequences revealed that the
      large subunit of the enzyme shares homology to glycyl radical enzymes,
      particularly near the predicted radical site. The highest similarity was observed
      with pyruvate formate lyases and related proteins. The radical-containing subunit
      of benzylsuccinate synthase is oxygenolytically cleaved at the site of the glycyl
      radical, producing the alpha'-subunit. The predicted cleavage site was verified
      using electrospray mass spectrometry. In addition, a gene coding for an
      activating protein catalysing glycyl radical formation was found. The four genes
      for benzylsuccinate synthase and the activating enzyme are organized as a single
      operon; their transcription is induced by toluene. Synthesis of the predicted
      gene products was achieved in Escherichia coli in a T7-promotor/polymerase
      system.

PMID- 9632264
TI  - Genetic uncoupling of the dsRNA-binding and RNA cleavage activities of the
      Escherichia coli endoribonuclease RNase III--the effect of dsRNA binding on gene
      expression.
AB  - RNase III, a double-stranded RNA-specific endonuclease, is proposed to be one of
      Escherichia coli's global regulators because of its ability to affect the
      expression of a large number of unrelated genes by influencing post
      transcriptional control of mRNA stability or mRNA translational efficiency. Here,
      we describe the phenotypes of bacteria carrying point mutations in rnc, the gene
      encoding RNase III. The substrate recognition and RNA-processing properties of
      mutant proteins were analysed in vivo by measuring expression from known RNase
      III-modulated genes and in vitro from the proteins' binding and cleavage
      activities on known double-stranded RNA substrates. Our results show that
      although the point mutation rnc70 exhibited all the usual rnc null-like
      phenotypes, unlike other mutations, it was dominant over the wild-type allele.
      Multicopy expression of rnc70 could suppress a lethal phenotype of the wild-type
      rnc allele in a certain genetic background; it could also inhibit the RNase III
      mediated activation of lambdaN gene translation by competing for the RNA-binding
      site of the wild-type endonuclease. The mutant protein failed to cleave the
      standard RNase III substrates in vitro but exhibited an affinity for double
      stranded RNA when passed through poly(rI):poly(rC) columns. Filter binding and
      gel-shift assays with purified Rnc70 showed that the mutant protein binds to
      known RNase III mRNA substrates in a site-specific manner. In vitro processing
      reactions with purified enzyme and labelled RNA showed that the in vivo dominant
      effect of the mutant enzyme over the wild-type was not necessarily caused by
      formation of mixed dimers. Thus, the rnc70 mutation generates a mutant RNase III
      with impaired endonucleolytic activity but without blocking its ability to
      recognize and bind double-stranded RNA substrates.

PMID- 9632265
TI  - Effects of the Escherichia coli DNA-binding protein H-NS on rRNA synthesis in
      vivo.
AB  - The Escherichia coli DNA-binding protein H-NS is known to interact specifically
      with the upstream region of ribosomal RNA transcription units, where it causes
      transcriptional repression in vitro. Here, we present results demonstrating the
      effect of H-NS on rRNA transcription in vivo. rRNA synthesis rates were compared
      in cells that differ in the expression of functional H-NS or FIS molecules. We
      could show that in the absence of H-NS derepression of rRNA synthesis occurs at
      low growth rates. During the cell cycle H-NS is responsible for the rapid shut
      off of rRNA synthesis at the end of the exponential phase. As it is known for FIS
      dependent activation, the inhibitory function of H-NS is specific for P1, the
      first of the tandem rRNA promoters. The effect of H-NS on rRNA synthesis was
      further assessed under stress conditions. While under osmotic upshift the
      reduction in rRNA synthesis is clearly H-NS-dependent, no such influence could be
      detected at cold shock. Determination of the cellular ppGpp concentrations
      revealed that H-NS does not mediate its function via alterations in the synthesis
      of the global effector ppGpp.

PMID- 9632266
TI  - Transmembrane topology and histidine protein kinase activity of AgrC, the agr
      signal receptor in Staphylococcus aureus.
AB  - The agr P2 operon in Staphylococcus aureus codes for the elements of a density
      sensing cassette made up of a typical two-component signalling system and its
      corresponding inducer. It is postulated that the autoinducer, a post
      translationally modified octapeptide generated from the AgrD peptide, interacts
      with a receptor protein, coded by agrC, to transmit a signal via AgrA regulating
      expression of staphylococcal virulence genes through expression of agr RNA III.
      We show by analysis of PhoA fusions that AgrC is a transmembrane protein, and
      confirm using Western blotting that a 46 kDa protein corresponding to AgrC is
      present in the bacterial membrane. This protein is autophosphorylated on a
      histidine residue only in response to supernatants from an agr+ strain, and can
      also respond to the purified native octapeptide. A recombinant fusion protein
      where most of the N-terminal region of AgrC is replaced by the Escherichia coli
      maltose-binding protein is also autophosphorylated in response to stimulation by
      agr+ supernatants or purified octapeptide. We conclude that AgrC is the sensor
      molecule of a typical two-component signal system in S. aureus, and that the
      ligand-binding site of AgrC is probably located in the third extracellular loop
      of the protein.

PMID- 9632267
TI  - Legionella pneumophila DotA protein is required for early phagosome trafficking
      decisions that occur within minutes of bacterial uptake.
AB  - Numerous intracellular bacterial pathogens modulate the nature of the membrane
      bound compartment in which they reside, although little is known about the
      molecular basis for this control. Legionella pneumophila is a bacterial pathogen
      able to grow within human alveolar macrophages and residing in a phagosome that
      does not fuse with lysosomes. This study demonstrates that the dotA product is
      required to regulate trafficking of the L. pneumophila phagosome. Phagosomes
      containing L. pneumophila dotA+ bacteria exhibited differential trafficking
      profiles when compared with isogenic dotA mutants. Phagosomes containing dotA
      mutants showed rapid accumulation of the lysosomal glycoprotein LAMP-1 as early
      as 5 min after uptake, whereas the majority of wild-type L. pneumophila
      phagosomes did not acquire LAMP-1. The association of LAMP-1 with phagosomes
      containing dotA mutant bacteria was concomitant with the appearance of the small
      GTP-binding protein Rab7 on the vacuolar membrane. These data demonstrate that
      phagosomes containing replication-competent L. pneumophila evade early endocytic
      fusion events. In contrast, the kinetics of LAMP-1 and Rab7 association indicate
      that the dotA mutants are routed along a well-characterized endocytic pathway
      leading to fusion with lysosomes. Genetic studies show that L. pneumophila
      requires DotA expression before macrophage uptake in order to establish an
      intracellular site for replication. However, the bacteria do not appear to
      require continuous expression of the DotA protein to maintain a replicative
      phagosome. These data indicate that DotA is one factor that plays a fundamental
      role in regulating initial phagosome trafficking decisions either upon or
      immediately after macrophage uptake.

PMID- 9632268
TI  - VIP (etoposide, ifosfamide and cisplatinum) as a salvage intensification program
      in relapsed or refractory Hodgkin's disease.
AB  - Forty-two patients with refractory (15 patients) or relapsed (27 patients)
      Hodgkin's disease (HD) were included in a prospective single center study
      evaluating the efficacy of a regimen VIP combining etoposide 75 mg/m2/day days 1
      5, ifosfamide 1.2 g/m2/day days 1-5 and cisplatinum 20 mg/m2/day days 1-5, one
      course every 4 weeks as salvage therapy in patients with refractory or relapsed
      Hodgkin's disease, potentially eligible for high-dose chemotherapy with
      reinjection of hematopoietic stem cells (HSC). If patients were considered
      chemosensitive after two courses of VIP, high-dose chemotherapy followed by the
      reinjection of HSC was planned. After two courses of VIP, 67% achieved an
      objective response including 38% complete responses. Overall, 28 patients went on
      to high-dose therapy with reinjection of HSC, and 46% of grafted patients are in
      a sustained complete remission. When the overall patient population is
      considered, 33% are in complete remission (CR) with a median follow-up of 37
      months. A CR of less than 12 months and refractory disease were associated with a
      poor survival. These results showed that the VIP regimen is effective in relapsed
      or refractory HD and allows high-dose therapy to be given in the case of most
      responding patients. However, results in patients with refractory disease or a
      first complete remission of less than 12 months need to be further improved.

PMID- 9632269
TI  - Marrow repopulating cells in mobilized PBPC can be serially transplanted for up
      to five generations or be remobilized in PBPC reconstituted mice.
AB  - We have evaluated the durability of engraftment and the potential of
      remobilization in mice reconstituted with mobilized peripheral blood progenitor
      cells (PBPC). Female mice which had been reconstituted with cytokine-mobilized
      PBPC from male donors were serially transplanted into second, third, fourth and
      fifth lethally irradiated female recipients at intervals of 6-10 months. Male
      derived hematopoiesis was determined in recipient mice at each serial
      transplantation. Male-positive CFCs were detected after 5 passages for 45 months,
      but declined from >95% at passage 1 to 74% at passage 2, 33% at passage 4, and
      28% at passage 5. Long-term survival also declined from 97% at passage 2 to 53%
      at passage 4, and 27% at passage 5. The results demonstrated that mobilized PBPC
      were able to provide engraftment for more than 45 months, but the engraftment
      provided by mobilized PBPC decreased at each serial passage. In addition, mice
      reconstituted with mobilized PBPC (at 1 year post transplantation) were treated
      with the same cytokines as in the primary mobilization (remobilization). The
      remobilized PBPC were harvested and transplanted into lethally irradiated
      secondary recipients. Male-derived CFCs were evaluated at 20 months post
      transplantation. Mice transplanted with PBPC remobilized with rhG-CSF or rhG-CSF
      plus rrSCF-PEG showed 70% and 89% male-positive CFCs respectively, demonstrating
      that mice reconstituted with mobilized PBPC could be remobilized and that the
      remobilized PBPC were also capable of providing long-term hematopoietic
      reconstitution. Our studies demonstrated that mobilized PBPC have extensive
      proliferative or self-renewal capacity to provide durable engraftment and that
      marrow repopulating cells in PBPC reconstituted mice can be remobilized,
      suggesting that patients who relapse after PBPC transplantation may be
      remobilized for a second transplantation to support additional chemotherapy.

PMID- 9632270
TI  - Bone marrow steady-state CD34+/CD71- cell content is a predictive value of rG-CSF
      mobilized CD34+ cells.
AB  - Thirty-four patients diagnosed with breast cancer were included in a prospective
      study evaluating the bone marrow (BM) CD34+/CD71- cell content, as a predictive
      parameter of the CD34+ cell mobilization after rG-CSF administration. Analysis of
      the concentration of medullary CD34+/CD71- cells before priming schedules was
      significantly related with the collection of CD34+ cells in apheresis day 1 (P =
      0.03, r = 0.36), apheresis day 1 + day 2 (P = 0.01, r = 0.42) or the total CD34+
      cells collected (P = 0.005, r = 0.47). A BM CD34+/CD71- cell concentration
      greater than or less than a cut-off value of 30/microl was significantly
      associated with the yield of CD34+ cells collected by cytapheresis procedures
      (mean values 3.12 x 10(6)/kg, and 2.19 x 10(6)/kg, respectively, P = 0.013).
      These results suggest that in breast cancer patients undergoing priming with rG
      CSF, steady-state BM CD34+/CD71- measurement is a relevant predictive parameter
      of CD34+ mobilization.

PMID- 9632271
TI  - Isolation and transplantation of autologous peripheral CD34+ progenitor cells
      highly purified by magnetic-activated cell sorting.
AB  - Peripheral stem cells were mobilized and collected in 26 pediatric patients with
      malignant diseases. A total of 47 leukaphereses were performed in the 26
      patients. The mean number of nucleated cells collected was 4.5 +/- 2.6 x 10(8)/kg
      and the number of CD34+ progenitors collected was 6.7 +/- 6.8 x 10(6)/kg. CD34
      positive selection was performed using a two-step method of magnetic-activated
      cell sorting (MACS) in 24 patients or a combination of an immunoaffinity column
      and MACS in two patients. The purity of the positively selected CD34+ progenitors
      was 98.8 +/- 0.7% and the number of isolated CD34+ cells was 6.5 +/- 5.9 x
      10(6)/kg. Thus, the mean recovery of CD34+ cells was 93 +/- 10%. In 22 of the 26
      patients, high-dose chemotherapy was performed with subsequent reinfusion of the
      highly purified CD34+ cells. In all 22 patients, a normal hematopoietic
      reconstitution was seen with a mean time of 12.4 +/- 2.7 days to reach >0.5 x
      10(9)/l neutrophils (range 8-19 days). The time to reach independence from
      platelet transfusion was 31.6 +/- 17.0 days (range 16-78 days). There were no
      transplant-related deaths. In summary, we have shown that mobilized peripheral
      CD34+ progenitors can be highly purified with a good recovery, and that
      reinfusion of these cells after high-dose chemotherapy results in a rapid,
      complete and sustained engraftment. We conclude that this method can be used for
      purging in any CD34-negative malignancies and for autologous T and B cell
      depletion in the treatment of autoimmune diseases with high-dose immunoablative
      therapy.

PMID- 9632272
TI  - Allogeneic bone marrow transplantation vs filgrastim-mobilised peripheral blood
      progenitor cell transplantation in patients with early leukaemia: first results
      of a randomised multicentre trial of the European Group for Blood and Marrow
      Transplantation.
AB  - In a multicentre trial involving 20 transplant centres from 10 countries
      haematopoietic stem cells were obtained either from the bone marrow of 33 sibling
      donors or from the peripheral blood of 33 such donors after administration of
      filgrastim (10 microg/kg/day). The haematopoietic stem cells were infused into
      their HLA-identical recipients suffering from acute leukaemias in remission or
      chronic myeloid leukaemia in chronic phase. PBPC donors tolerated filgrastim
      administration and leukapheresis well with the most frequent side-effects being
      musculoskeletal pain, headache, and mild increases of LDH, AP, Gamma-GT or SGPT.
      Pain and haematoma at the harvest site and mild anaemia were the most frequent
      complaints of BM donors. Severe or life-threatening complications were not seen
      with any type of harvest procedure. Time to platelet recovery greater than 20 x
      10(9)/l was 15 days (95% confidence interval (CI) 13-16 days) in the PBPCT group
      and 19 days (CI 16-25) in the BMT group. Time to neutrophil recovery greater than
      0.5 x 10(9)/l was 14 days (CI 12-15 days) in the PBPCT group as compared to 15
      days (CI 15-16 days) in the BMT group. The numbers of platelet transfusions
      administered to PBPCT and BMT patients were 12 (range: 1-28) and 10 (range: 3
      39), respectively. Sixteen patients (48%) transplanted with bone marrow and 18
      patients (54%) transplanted with PBPC developed acute GVHD of grades II-IV; acute
      GVHD of grades III or IV developed in six (18%) and seven (21%) patients,
      respectively. Kaplan-Meier plots for transplant-related mortality until day 100
      and leukaemia-free survival at a median of 400 days after BMT or PBPCT showed no
      significant differences. Administration of filgrastim and leukapheresis in normal
      donors were feasible and well tolerated. The number of days with restricted
      activity and of nights spent in hospital was lower in donors of PBPC.
      Transplantation of PBPC to HLA-identical siblings with early leukaemia resulted
      in earlier platelet engraftment. The incidence of moderate to severe acute GVHD,
      transplant-related mortality, and leukaemia-free survival did not show striking
      differences. Further investigation of allogeneic PBPCT as a substitute for
      allogeneic BMT is warranted.

PMID- 9632273
TI  - Early vs delayed administration of G-CSF following autologous peripheral blood
      stem cell transplantation.
AB  - It is well established that recombinant human G-CSF accelerates neutrophil
      recovery following autologous peripheral blood stem cell transplantation (PBSCT).
      However, the optimal timing of G-CSF following transplantation remains unknown.
      We have conducted a retrospective analysis of patients treated with either early,
      day +1 (n = 42) or delayed, day +4 (n = 39) administration of G-CSF following
      autologous PBSCT for a variety of hematologic malignancies and solid tumors. G
      CSF was given at a dose of 5 microg/kg/day i.v. as a 2 h infusion beginning
      either day +1 or day +4 following PBSC infusion and continued until the total
      white blood count (WBC) was >10 x 10(9)/l. The numbers of transplanted CD34+
      cells were similar in each group. Treatment with early administration of G-CSF
      resulted in a significantly shorter time to an absolute neutrophil count (ANC) of
      >0.5 x 10(9)/l (8.5 vs 10.0 days, P < 0.0003) and shorter length of
      hospitalization (16.3 vs 18.6 days, P < 0.0008), a trend towards a reduced
      incidence of infection (53 vs 72%) and a significant decrease in the duration of
      non-prophylactic antibiotic (NPA) therapy for neutropenic fever (4.0 vs 7.5 days,
      P < 0.009) compared to day +4 administration. Despite the additional cost of G
      CSF, the reduction in the hospitalization and NPA therapy with early G-CSF
      administration resulted in 11% cost savings overall per transplant at our
      institution.

PMID- 9632274
TI  - Peripheral blood stem cell autografts for the treatment of children over 1 year
      old with stage IV neuroblastoma: a long-term follow-up.
AB  - This is the first report of the long-term therapeutic results in 22 children more
      than 1 year old with stage IV neuroblastoma who were treated with autologous
      peripheral blood stem cell transplantation (PBSCT). The median age of the
      patients at PBSCT was 4 years (1 to 10 years) and seven of the 17 patients who
      were evaluated for N-myc amplification were positive. PBSC were collected by a
      median of four aphereses per patient. The patients underwent PBSCT from 6 to 21
      months after the start of therapy (median 10.5 months) at which time 13 patients
      were in CR, seven were in PR, and two had refractory disease. Multi-drug therapy
      using the 'high-MEC' regimen consisting of carboplatinum (400 mg/m2) and VP-16
      (200 mg/m2) on days -7 to -4, and melphalan (90 mg/m2) on days -3 and -2, was the
      primary cytoreductive regimen. The median number of infused MNC and CFU-GM was,
      respectively, 4.3 x 10(8)/kg and 2.4 x 10(5)/kg. After PBSCT, three patients died
      of regimen-related toxicities and one patient who was transplanted with
      refractory disease died of disease progression without any benefit from
      transplantation. Hematological recovery was evaluated in 21 patients, excluding
      one early death. The median number of days required to achieve an AGC of >0.5 x
      10(9)/l and platelet count of >50 x 10(9)/l were, respectively, 11 and 46. Eleven
      patients relapsed 3 to 50 months after PBSCT, and currently seven patients (5/13
      who were transplanted in CR and 2/7 in PR) are surviving disease-free at 52 to 84
      months. Although the retrospective nature of this study and several variables
      prevent a meaningful analysis, the overall results still support the feasibility
      of developing a prospective study of PBSCT with a larger number of children with
      high-risk neuroblastoma.

PMID- 9632275
TI  - Autologous bone marrow transplantation for childhood acute lymphoblastic
      leukaemia in Italy. AIEOP/FONOP-TMO Group. Italian Association of Paediatric
      Haemato-Oncology.
AB  - From January 1984 to December 1994, ABMT was performed on 154 children (101
      males, 53 females; median age 10, range 3-21 years) with ALL and registered for
      BMT by the AIEOP (Italian Association of Paediatric Haemato-Oncology). All
      patients were in CR: 98 were in 2nd CR and 56 were in >2nd CR. Fifteen children
      (9.7%) died of transplant-related mortality. Ninety-five patients (61.6%)
      relapsed at a median of 5 (range 1-42) months after ABMT. The 8-year EFS
      according to pre-BMT status was 34.6% (s.e. 4.9) for 2nd CR patients and 10.6%
      (s.e. 5.6) for patients in >2nd CR. By univariate analysis, site of relapse
      (isolated extramedullary (IE) vs BM: EFS = 68.5% vs 18.2%; P < 0.0001) and TBI
      containing regimen (TBI vs no TBI: EFS = 48.1 vs 15.4%; P = 0.0023) were
      significant factors for 2nd CR patients. When the 2nd CR subset with BM
      involvement was analysed, TBI became insignificant (EFS = 25.4 vs 11.8%). No
      factors influenced EFS in patients in >2nd CR. By multivariate analysis, site of
      relapse was the only significant factor in 2nd CR patients (P < 0.0001). In
      conclusion, ABMT is an effective treatment after one early IE relapse. Few
      patients can be rescued after BM relapse.

PMID- 9632276
TI  - Allogeneic or autologous stem cell transplantation following salvage chemotherapy
      for adults with refractory or relapsed acute lymphoblastic leukemia.
AB  - Over a 9-year period 37 consecutive adults with primary refractory (n = 13) or
      first relapse of ALL (n = 24) received an intensive salvage chemotherapy regimen
      with the final intention of undergoing stem cell transplantation (SCT). Twenty
      nine patients who achieved complete remission (CR) were assigned to receive
      autologous SCT (autoSCT) or allogeneic SCT (alloSCT) based on age and
      availability of a histocompatible sibling. Of the 19 patients assigned to
      autoSCT, 10 did not reach the transplant due to early relapse (n = 9) or fungal
      infection (n = 1), and nine were transplanted a median of 2.5 months (1-8) from
      CR, eight with an immunologically purged graft. One patient died early from ARDS
      and eight relapsed 2-30 months post-SCT. Three of the 10 patients assigned to
      alloSCT relapsed early, but all 10 received the assigned transplant a median of
      2.5 months (1-7) from CR. Four died from transplant-related complications 0.7-12
      months post-SCT, and six are alive and disease-free 9.7-92.6 months after the
      procedure. In an intention-to-treat analysis, the mean overall survival from CR
      for those assigned to autoSCT and alloSCT are 11.3 months (0.5-34.3) and 60.1
      (2.3-98.3), respectively (log-rank, P < 0.01). Only 65% of patients who reached
      CR and 51% of the initial 37 cases underwent the intended SCT. We conclude that
      few adults with refractory or relapsed ALL actually reach SCT in CR even when the
      protocol used is designed for this purpose. AutoSCT appears to offer little
      benefit in this setting, and an alloSCT from a related or unrelated donor should
      be rapidly pursued after achieving CR.

PMID- 9632277
TI  - Chemotherapy-induced mobilization of karyotypically normal PBSC for autografting
      in CML.
AB  - High-dose chemotherapy with autologous transplantation of in vivo purged PBSC is
      a new and interesting therapeutic option for CML patients not eligible for
      allogeneic transplantation. We investigated the feasibility and toxicity of this
      approach in 57 patients with Ph-positive CML. For mobilization of Ph-negative
      PBSC, patients were treated either with '5 + 2/7 + 3'- type chemotherapy or with
      'mini-ICE/ICE' chemotherapy followed by administration of G-CSF. Fourteen
      patients were in early chronic phase, 30 patients in late chronic phase and 13
      patients in accelerated phase (AP) or blast crisis (BC). Cytogenetic responses in
      the PBSC harvests were dependent on both disease stage and type of chemotherapy:
      in late chronic phase and AP/BC, a complete or major cytogenetic response could
      be obtained in nine out of 13 patients treated with 'mini-ICE/ICE' but only in
      three out of 23 patients treated with '5 + 2/7 + 3' chemotherapy. However, in
      early chronic phase a Ph-negative autograft could be obtained in three out of
      eight patients upon mobilization with '5 + 2' chemotherapy. Thirty-one patients
      underwent PBSC transplantation and all of them successfully engrafted. Post
      transplant cytogenetic analysis was available on 21 cases, of whom seven achieved
      a complete or major cytogenetic response, with two minor cytogenetic remissions.
      One patient (1/57) in blast crisis died during mobilization therapy (1.8%).
      Transplantation related mortality was 0%. This study demonstrates that
      mobilization of Ph-negative PBSC after myelosuppressive chemotherapy is feasible
      in CML patients and is associated with acceptable toxicity. Autologous
      transplantation of in vivo purged PBSC is a safe procedure with rapid and
      complete hematopietic recovery.

PMID- 9632278
TI  - Reduced progression-free survival in elderly patients receiving intensification
      with autologous peripheral blood stem cell reinfusion for multiple myeloma.
AB  - Between 1990 and 1997, 55 patients with high risk multiple myeloma underwent high
      dose therapy with peripheral blood stem cell transplantation. Intensification
      consisted of high-dose L-PAM in 54 patients, and 15 patients underwent a second
      high-dose treatment. Thirty patients received total body irradiation. Twenty
      patients were more than 60 years old. Thirty-five patients were intensified
      during first response. The overall response rate was 78%. There were four toxic
      deaths. The median overall survivals after intensification and after first
      treatment of myeloma were greater than 48 months and 71 months, respectively.
      Conversely freedom from progression after intensification was short, with a
      median of 22 months. Freedom from progression was significantly shorter in
      patients older than 60 (12 months), and in patients who had received more than 75
      mg/m2 of L-PAM before intensification (16 months). Although intensification is
      feasible in elderly patients the benefit appears to be reduced in this subgroup
      of patients. Prior therapy with high cumulative doses of L-PAM should be avoided
      in patients who will receive high-dose L-PAM for therapeutic intensification.

PMID- 9632279
TI  - Successful allogeneic bone marrow transplantation in selected patients over 50
      years of age--a single institution's experience.
AB  - As allogeneic bone marrow transplantation (BMT) is a procedure with a higher risk
      of morbidity and mortality in older patients, many institutions place a limit of
      50 to 55 years for allogeneic BMT. Consequently, older patients may not be
      offered potentially curative treatment for otherwise poor prognosis diseases such
      as AML or myelodysplastic syndrome. We compared the outcome of 59 patients aged
      over 50, 124 aged 40-50, and 253 aged 18-39 years who underwent allogeneic BMT in
      our institution between August 1987 and April 1996. Our results show little
      influence of age on outcome when comparing patients over 50 years with patients
      40-50 years. Apart from an initial higher transplant mortality rate, overall
      survival was not significantly different between the three age groups. The 1-year
      and 2-year overall survival rates were 57% and 48%, 57% and 48%, and 62% and 58%
      for the >50 years, 40-50 years, and <40 years patients, respectively. The
      incidence of GVHD was also comparable. We conclude that allogeneic BMT can be
      performed in selected patients over the age of 50 years with acceptable morbidity
      and mortality and that older patients should not be denied this treatment based
      on age alone.

PMID- 9632280
TI  - Paroxysmal atrial fibrillation after high-dose melphalan in five patients
      autotransplanted with blood progenitor cells.
AB  - Among the drugs used in conditioning regimens for stem cell transplantation, high
      dose melphalan (HDM) plays an important role for both its strong myeloablative
      effect and for its favourable dose-response ratio. Here we report five cases of
      high frequency atrial fibrillation (AF) developing after HDM. Duration of the
      arrhythmia was always very short, beginning at variable intervals after the
      administration of HDM, in the absence of other factors potentially able to
      trigger AF. In all patients sinus rhythm was restored within 72 h and the follow
      up did not show any cardiac damage. To the best of our knowledge, this side
      effect has never been reported to occur after HDM.

PMID- 9632281
TI  - Adoptive immunotherapy for relapse of chronic myeloid leukemia after allogeneic
      bone marrow transplant: equal efficacy of lymphocytes from sibling and matched
      unrelated donors.
AB  - Lymphocyte transfusion from the marrow donor (DLT) is well established as an
      effective therapy for relapse of CML post allogeneic BMT. Reports thus far have
      been mostly limited to patients who received DLT from a matched sibling donor. We
      compared the efficacy and toxicity of DLT in 30 patients who were treated with
      cells from their HLA-identical sibling (n = 18) or from their phenotypically HLA
      matched unrelated marrow donor (n = 12). The overall probability of obtaining a
      cytogenetic remission was 69% (95%CI: 51-83%) and was not significantly different
      between the two groups. The disease stage at the time of DLT was the only factor
      associated with cytogenetic remission by multivariate analysis; patients treated
      in cytogenetic or molecular relapse (n = 11) were seven times more likely (RR =
      7.4, 95%CI: 2.4-22.4, P = 0.0005) to respond compared to patients treated for
      hematologic relapse (n = 19). There was a trend towards more acute GVHD II-IV in
      the unrelated donor group (58 vs 39%, P = 0.09), but the probability of
      developing extensive chronic GVHD was not significantly different (56 vs 39%, P =
      0.4). We conclude that transfusion of donor cells from HLA-matched volunteer
      donors does not appreciably increase the risk of GVHD compared with transfusion
      of cells from HLA-identical siblings in patients with CML who relapse following
      allogeneic BMT. Conversely, there is no evidence for an increased graft-versus
      leukemia effect after DLT from volunteer donors.

PMID- 9632282
TI  - Primary human herpes virus 6 infection transmitted from donor to recipient
      through bone marrow infusion.
AB  - An 8.5-month-old boy with Wiskott-Aldrich syndrome received a sibling matched
      bone marrow transplant from his healthy non-identical twin brother. The donor had
      primary human herpes virus 6 (HHV-6) infection around the time of bone marrow
      donation. The recipient had hepatitis in the first week and then developed fever
      and rash on day 18. Skin biopsy was shown to have HHV-6 antigen and his
      peripheral blood leukocytes were HHV-6 DNA positive. He engrafted on day 18 but
      the ANC dropped from 5.5 x 10(9)/l (day 23) to 0.48 x 10(9)/l (day 34) with
      persistent HHV-6 DNAemia. Bone marrow on day 35 was positive for HHV-6 DNA. He
      was treated with G-CSF and ganciclovir with good response. He later had
      pneumonitis which was treated empirically with foscarnet, ceftazidime and
      clarithromycin.

PMID- 9632283
TI  - Successful management of adult respiratory distress syndrome (ARDS) after high
      dose chemotherapy and peripheral blood progenitor cell rescue by non-invasive
      ventilatory support.
AB  - A 34-year-old man suffering from Hodgkin's disease underwent high-dose
      chemotherapy (CBV) followed by transplantation of autologous peripheral blood
      stem cells. On day +6 after peripheral blood stem cell transplant (PBSCT)
      bacterial pneumonia developed. Along with rapid engraftment during stimulation
      with G-CSF adult respiratory distress syndrome (ARDS) developed within 4 days.
      High-flow CPAP (continuous positive airway pressure) ventilation via a sealed
      face-mask was initiated. The patient tolerated the sealed face-mask very well,
      and CPAP was continuously administered for 4 days, thus avoiding intubation. High
      flow CPAP may offer a therapeutic alternative in selected patients with
      respiratory compromise after PBSCT.

PMID- 9632284
TI  - Transmission of an anti-RhD alloantibody from donor to recipient after ABO
      incompatible BMT.
AB  - We report a bone marrow transplant which was HLA matched, with major and minor
      ABO and minor RhD incompatibility (anti-RhD antibody) between the donor and
      recipient. When engraftment occurred, the recipient developed an anti-RhD
      antibody of donor origin detected by direct and indirect antiglobulin tests (DAT,
      IAT) and showed signs of mild hemolytic anemia. With the disappearance of the
      recipient RBCs, the DAT became negative and the hemolysis disappeared, while the
      anti-RhD alloantibody persisted in the patient's serum. This case emphasizes the
      importance of close immuno-hematological monitoring in patients undergoing
      allogeneic BMT with ABO-RhD incompatibility between recipient and donor.

PMID- 9632285
TI  - Monocytes are the likely candidate 'stromal' cell in G-CSF-mobilized peripheral
      blood.

PMID- 9632286
TI  - Studying spreading pattern in Hodgkin's disease: is it relevant to modern cancer
      treatment?

PMID- 9632287
TI  - Contiguous pattern spreading in patients with Hodgkin's disease.
AB  - BACKGROUND: In 1966, Rosenberg and Kaplan hypothesized that Hodgkin's disease
      (HD) arises at a discrete primary site and subsequently spreads in a predictable
      manner via functionally contiguous lymph nodes. However, their results were not
      statistically evident. It was our aim to describe the spreading in the lymphatic
      system more precisely and to confirm their postulate. METHODS: Between 1971 and
      1992, 297 patients underwent pathological staging for HD. Our subsequent
      evaluation was restricted to the 236 cases with cervical involvement (65
      bilateral, 80 dextral and 91 sinistral), those with lymph nodes on the right side
      (65 + 80 = 145) being analyzed separately from those with tumours on the left (65
      + 91 = 156). Spreading via the lymphatic system was assessed by scoring of the
      number of involved and uninvolved nodes in six regions, which are functionally
      contiguous in the lymph system but not necessarily anatomically neighboured. The
      number of 'gaps' (i.e. missed nodes) observed according to a systematic spreading
      model was compared with that expected (probability model) if a random course had
      been followed. RESULTS: Of the 156 patients with left cervical HD, 117 (75%) had
      para-aortic or spleen involvement, 90 (58%) had mediastinal involvement, 65 (42%)
      had right cervical involvement, 50 (32%) had axillary involvement and 23 (15%)
      had inguinal involvement. Of the 145 patients with right cervical HD, 112 (77%)
      had mediastinal involvement, 89 (61%) had para-aortic or spleen involvement, 65
      (44%) had left cervical involvement, 44 (30%) had axillary involvement and 16
      (11%) had inguinal involvement. In patients with left or right cervical lymph
      nodes, the proportions observed with gaps in the spreading were 37 and 27% (SE
      7%), respectively, whereas the corresponding values of gaps expected in a
      probability model if a random course of spreading had been followed would have
      been 84 and 73% (P = 0.0001 and 0.0001, respectively). CONCLUSION: Our data
      support the concept that HD spreads in a predictable manner via functionally
      contiguous lymph nodes. In patients with right cervical lymph nodes, HD spreads
      via the upper mediastinum and pulmonary hila to the upper abdominal nodes and the
      spleen. In those with left cervical tumours, HD spreads directly to the abdomen
      (bypassing the mediastinum), then upward again via the pulmonary hila and upper
      mediastinum to the neck region (bilateral involvement) and from here it proceeds
      to the axillary nodes. Finally the inguinal nodes are involved.

PMID- 9632288
TI  - Epicondylopathia humeri (EPH) and peritendinitis humeroscapularis (PHS):
      evaluation of radiation therapy long-term results and literature review.
AB  - BACKGROUND: The effectiveness of radiotherapy (RT) for degenerative inflammatory
      disorders has been clinically documented in historical studies, but long-term
      follow-up and assessment with objective criteria are still not available.
      PATIENTS AND METHODS: From 1986 to 1991, 200 consecutive patients with
      symptomatic epicondylopathia humeri (EPH, n = 104) and peritendinitis
      humeroscapularis (PHS, n = 96) were referred to our clinic. All patients were
      refractory to conventional therapy prior to irradiation. One hundred fifty-six
      patients with 192 sites (due to bilateral symptoms) received a full treatment
      course and were available for long-term follow-up, i.e. 83 patients with 93
      elbows and 73 patients with 89 shoulders. The treatment response was evaluated
      with regard to pain symptoms grouped into five categories (pain at strain, pain
      at night, persistent pain during daytime, pain at rest and morning stiffness) and
      four grades (none, mild, moderate and severe) and with regard to established
      orthopedic scores (Morrey score and Constant and Murley score). The analysis was
      performed before and 6 weeks after RT and at last follow-up. All joints received
      two RT series applied in three weekly fractions (EPH, 6 x 1 Gy (total 12 Gy);
      PHS, 6 x 0.5 Gy (total 6 Gy)). The second RT series started 6 weeks after the
      first RT series. The minimum follow-up was 1 year for both groups and the mean
      follow-up reached 4 years (range 1-8 years). RESULTS: Fifty elbows (43 patients)
      and 44 shoulders (39 patients) achieved complete pain relief in all pain
      categories; 24 elbows and 28 shoulders substantially improved, i.e. had only
      minor symptoms. Thus, 74 elbows and 72 shoulders responded to RT. Nineteen elbows
      (17 patients) had surgery after RT due to persisting symptoms or subjective
      dissatisfaction; 17 shoulders (12 patients) were non-responders and five of those
      were operated on; seven elbows and one shoulder were completely free of pain
      after surgery. The mean Morrey score improved by 18 points (from 78 to 96) and
      the mean Constant and Murley score improved by 48 points (from 18 to 66). Two
      cases worsened according to the Morrey score and one case worsened according to
      the Constant and Murley score. Bi- and multivariate analysis revealed two factors
      with negative prognostic value on treatment outcome, i.e. EPH, long symptom
      interval prior to RT and long-term immobilization with plaster (P < 0.05) and
      PHS, long symptom interval prior to RT and lack of pain intensification during
      the first RT course (P < 0.05) were poor prognostic factors. CONCLUSION: RT is
      highly effective for refractory EPH and PHS. Structured pain scores and
      quantitative orthopedic scores are important for evaluation. Prognostic factors
      for outcome can be established. Due to minimal side effects and low costs, RT
      represents an excellent treatment compared to conventional methods of treatment
      and surgery in the chronic disease.

PMID- 9632289
TI  - Quality assurance in radiation oncology. A study of feasibility and impact on
      action levels of an in vivo dosimetry program during breast cancer irradiation.
AB  - BACKGROUND AND PURPOSE: The study was aimed at investigating the feasibility and
      accuracy of an in vivo quality assurance program in radiotherapy. Breast
      irradiation was found to be a relevant clinical model due to the fairly good
      uniformity of the irradiated tissue. MATERIALS AND METHODS: The investigation was
      based on an extension of the method described by Leunens et al. (Leunens, G., van
      Dam, J., Dutreix, A. and van der Schueren, E. Quality assurance in radiotherapy
      by in vivo dosimetry. 1. Entrance dose measurements, a reliable procedure.
      Radiother. Oncol. 17: 141-151, 1990; Leunens, G., van Dam, J., Dutreix, A. and
      van der Schueren, E. Quality assurance in radiotherapy by in vivo dosimetry. 2.
      Determination of the target absorbed dose. Radiother. Oncol. 19: 73-87, 1990; van
      Dam, J. and Marinello, G. Methods for in vivo dosimetry in external radiotherapy.
      Physics for clinical radiotherapy. ESTRO Booklet n. 1 (Garant), 1994),
      determining the absorbed dose at any point on the central axis from a measurement
      of entrance and exit doses with individually calibrated and corrected diodes.
      Treatment accuracy (delta) was quantified as the ratio of the measured and the
      expected isocentre dose from the treatment planning system (TPS). RESULTS: A
      preliminary study was carried out on a Plexiglas slab phantom to test the method
      ending with a frequency distribution of delta with a mean of 0.04 +/- 0.05% and a
      standard deviation (SD) of 0.83 +/- 0.04%. In the in vivo study, 101 patients
      irradiated with two tangential fields were included in the protocol over a 1-year
      period. The total number of patient set-ups analyzed was 421 giving a
      distribution of delta with a mean of -1.3 +/- 0.2% and an SD of 2.7 +/- 0.1%
      without any correction. Taking into account temperature effects and set-up errors
      as SSD accuracy and diodes positioning it was possible to implement an off-line
      correction method leading to a final distribution with a mean of -1.9 +/- 0.2%
      and an SD of 2.4 +/- 0.1%. Individual cases with large deviations were detected
      and evaluated and actions were undertaken whenever possible. CONCLUSIONS: The
      study showed that diodes can be easily used by radiographers in an accurate in
      vivo quality assurance (QA) program and that an accuracy level of 3% at 1 SD can
      be reached on average. Attention and action levels can also be identified and
      careful evaluation of positioning and morphological variations during treatment
      should be part of a comprehensive QA program.

PMID- 9632290
TI  - Quality assurance of the EORTC radiotherapy trial 22931 for head and neck
      carcinomas: the dummy run.
AB  - PURPOSE: A dummy run was organized to test the compliance of participating
      centres with the guidelines of EORTC protocol 22931, which compares high dose
      radiotherapy with concomitant radiochemotherapy in a postoperative setting for
      patients presenting with locally advanced head and neck carcinomas. METHODS: In a
      first step the participants (seven centres, six replies) were asked to define the
      planning target volume (PTV) in a given patient on the basis of clinical,
      surgical and radiological (CT-images) data-sets and according to the protocol
      guidelines. In a second phase a series of CT-reconstructed slices with on- and
      off-axis PTV outlines were sent to 11 centres (10 replies), which were asked to
      plan a treatment following the recommendations made in the frame of the trial.
      RESULTS: The first step of this dummy run emphasized wide intercentre variations
      in PTV extensions. This fact raises the question of the reproducibility when
      pooling patients in multicentric trials. The second step indicated a large
      variability in the field arrangements which was left to the discretion of the
      investigators. Only three out of 10 of the institutions followed the ICRU 50
      recommendations for dose reporting. Moreover, protocol requirements were not met
      for dose distribution homogeneity in any centre. CONCLUSIONS: In order to reduce
      intercentre treatment heterogeneities, several actions have been taken by the
      EORTC Radiotherapy Group, e.g. amendments have been brought to protocol 22931
      regarding a better definition of clinical and planning target volumes.
      Furthermore, a stricter application of the ICRU 50 recommendations for dose
      reporting has been sought.

PMID- 9632291
TI  - The implementation of in vivo dosimetry in a small radiotherapy department.
AB  - PURPOSE: In vivo dosimetry has been shown in a number of evaluation studies,
      generally carried out in larger academic centres, to be a reliable method of
      checking the overall treatment accuracy. The object of this study was to
      investigate whether it was possible and useful to perform in vivo dosimetry in a
      small radiotherapy department and to detect if there were any systematic errors
      in the overall treatment set-up. MATERIALS AND METHODS: All patients were treated
      on a cobalt-60 unit equipped with a verification system. Six hundred fifty
      entrance dose measurements were performed with silicon diodes. RESULTS: The
      analysis showed a mean deviation of -1.3%. This negative deviation was mainly due
      to the mean deviation obtained in the treatment of head and neck (-1.6%) or
      breast (-2.5%) cancer patients. The results for pelvic or lung irradiation showed
      almost no deviation (-0.8 to 0.43%). Further investigation showed that the
      negative values for head and neck or breast irradiation were due to the
      irradiation technique; the lack of scattering material causes a reduction of the
      dose at the reference point, which is not taken into consideration by the
      treatment planning system. By performing in vivo dosimetry, we were also able to
      detect two large errors in 650 measurements and could prevent erroneous
      treatment. CONCLUSION: Even when the overall treatment set-up is very accurate,
      in vivo dosimetry is very useful in a small department since only a small effort
      can detect and prevent errors.

PMID- 9632292
TI  - Off-line verification of the day-to-day three-dimensional table position
      variation for radiation treatments of the head and neck region using an
      immobilization mask.
AB  - Variation in the table height position for 175 treatments of 167 patients was
      calculated as a measure for day-to-day set-up precision in 2063 treatment
      sessions and resulted in a median standard deviation of 1 mm. The median standard
      deviations of table longitudinal and lateral position were 3 and 5 mm,
      respectively.

PMID- 9632293
TI  - Dose calculation and dosimetry tests for clinical implementation of 1D tissue
      deficit compensation by a single dynamic absorber.
AB  - BACKGROUND AND PURPOSE: In this study the possibilities for implementing 1D
      tissue-deficit compensation techniques by a dynamic single absorber were
      investigated. This research firstly involved a preliminary examination on the
      accuracy of a pencil beam-based algorithm, implemented for irregularly shaped
      photon beams in our 3D treatment planning system (TPS) (Cadplan 2.7, Varian
      Dosetek Oy), in calculating dose distributions delivered in ID non-uniform
      fields. Once the reliability of the pencil beam (PB) algorithm for dose
      calculations in non-uniform beams was verified, we proceeded to test the
      feasibility of tissue-deficit compensation using our single absorber modulator.
      As an example, we considered a mantle field technique. MATERIALS AND METHODS: To
      evaluate the accuracy of the method employed in calculating dose distributions
      delivered in 1D non-uniform fields, three different fluence profiles, which could
      be considered as a small sample representative of clinically relevant
      applications, were selected. The incident non-uniform fluences were simulated by
      the sum of simple blocked fields (i.e. with rectangular 'strip' blocks, one per
      beam) properly weighed by the 'modulation factors' Fi, defined in each interval
      of the subdivided profile as the ratio between the desired fluence and the open
      field fluence. Depth dose distributions in a cubic phantom were then calculated
      by the TPS and compared with the corresponding doses (at 5 and 10 cm acrylic
      depths) delivered by the single absorber modulation system. In the present
      application, the absorber speed profile able to compensate for the tissue deficit
      along the cranio-caudal direction and then homogenizing the dose distribution on
      a 'midline' isocentric plane with sufficient accuracy can be directly derived
      from anatomic data, such as the SSDs (source-skin distances) along the patient
      contour. The compensation can be verified through portal dosimetry techniques
      (using a traditional port film system). RESULTS: The technique was tested in
      isocentric conditions on the humanoid RANDO phantom in a clinically suitable
      situation. The agreement between expected/calculated and measured incident/exit
      dose profiles was found to be within 4%, with deviations generally around 1-2%.
      As for the PB accuracy investigation for dose calculations in non-uniform fields,
      calculated versus measured dose profiles were found to be in good agreement,
      indicating a satisfactory accuracy of the method employed for dose calculation in
      1D non-uniform photon beams. A better performance should be expected if the
      incident fluences could be directly inserted in the TPS. CONCLUSIONS: The results
      show that the proposed technique should be sufficiently reliable for clinical
      application. The main advantages are its simplicity and the possibility of
      application on Linacs which have no complex options for dynamic control of
      collimators.

PMID- 9632294
TI  - Geometric and dosimetric analysis of multileaf collimation conformity.
AB  - BACKGROUND AND PURPOSE: There is concern over the stepped edges of multileaf
      collimator (MLC) fields for target coverage compared with those of cerrobend.
      Despite recent reports dispelling this concern, users are still cautious when
      using MLCs for small fields. Leaf orientation can be a problem if one is required
      to orient the leaves along an axis not ideal for conformity (such as dynamic or
      universal wedge cases). In this study we examined the dependence of MLC field
      conformity on field size and elongation. MATERIALS AND METHODS: We examined
      circles of varying diameter and ellipses of varying eccentricity with leaves
      oriented along the major and minor axes of ellipses. The tests were both
      geometric, comparing areas of overblocking or underblocking (leaves inside and
      outside the field), and dosimetric, using radiographic films at depth in the
      beam's eye view plane. RESULTS: For the geometric comparison there is a rapid
      increase in non-conformity, defined as the percentage of overblocking or
      underblocking area, as the circle diameter decreases. For ellipses, when the
      leaves move along one axis direction, the conformity does not depend on the
      diameter of the same axis, but instead improves as the dimension of the axis in
      the non-leaf motion direction increases. The best conformity is achieved when the
      maximum number of leaves is used to shape the field. When the dosimetry is
      analyzed, the predictability of these trends decreases due to the impact of
      undulations (scatter), leaf inaccuracies and dosimetric uncertainties.
      CONCLUSIONS: We recommend that for small round fields MLC should be used with
      caution and that for ellipses the direction of leaf movement should be aligned
      with the minor axis whenever possible. Though these experiments are for idealized
      geometries, the observations can be applied to clinical fields. An MLC with a
      thinner leaf width could be beneficial for small round fields.

PMID- 9632295
TI  - 3D conformal intensity-modulated radiotherapy planning: interactive optimization
      by constrained matrix inversion.
AB  - BACKGROUND AND PURPOSE: This paper presents a method for interactive optimization
      of 3D conformal intensity-modulated radiotherapy plans employing a quadratic
      objective that also contains dose limitations in the organs at risk. This
      objective function is minimized by constrained matrix inversion (CMI) that
      follows the same approach as the gradient technique using matrix notation.
      MATERIALS AND METHODS: Sherouse's GRATIS radiotherapy design system is used to
      determine the outlines of the target volume and the organs at risk and to input
      beam segments which are given by the beam segmentation technique. This technique
      defines the beam incidences and the beam segmentation. The weights of the
      segments are then calculated using a quadratic objective function and CMI. The
      objective function to be minimized consists of two components based on the
      planning target volume (PTV) and the organ at risk (OAR) with an importance
      factor w associated with the OAR. RESULTS: Optimization is tested for concave
      targets in the head and neck region wrapping around the spinal cord. For a
      predefined w-value, segment weights are optimized within a few seconds on a DEC
      Alpha 3000. In practice, 5-10 w-values have to be tested, making optimization a
      less than 5 min procedure. This optimization procedure predicts the possibility
      of target dose escalation for a tumour in the lower neck to 120-150 Gy without
      exceeding the spinal cord tolerance, whereas human planners could not increase
      the dose above 65-80 Gy. CONCLUSIONS: Treatment plans optimized using a quadratic
      objective function and the CMI algorithm are superior to those which are
      generated by human planners. The optimization algorithm is very fast and allows
      interactive use. Quadratic optimization by CMI is routinely used by clinicians at
      the Division of Radiotherapy, U.Z.-Gent.

PMID- 9632296
TI  - A new mold material for customized patient positioning in radiotherapy.
AB  - MATERIALS: The new material consists of polystyrene beads coated in a
      polymerizing substance that when dampened, hardens within 10 min. RESULTS AND
      CONCLUSIONS: It has a density of less than a tenth of that of water and so is
      light-weight, a CT number of less than -800 and a minimal effect on the build-up
      of megavoltage photon beams.

PMID- 9632297
TI  - A semi-empirical method for calculating the effect of air gap space on output
      factors on electron beam dose distributions.
AB  - BACKGROUND: A simple approach to calculate the effect of air gap on output
      factors on electron beam dose distribution is presented. METHODS: The method
      accounts for variations of pencil beam parameters using a model developed by
      Bruinvis et al. [4,5]. The evaluation of this method is based on measurements of
      the output factors at various distances between the final collimating device and
      the phantom surface. RESULTS: Comparison of calculations and measurements of
      output factors for various cone sizes and 0, 2 and 4 cm air gaps show agreement
      to within approximately 1.5% for electron energies of 6-13.5 MeV and field sizes
      of 5.3-10 cm in diameter. CONCLUSION: The accuracy of this semi-empirical method
      can be considered clinically acceptable and reduces the amount of experimental
      work needed.

PMID- 9632298
TI  - The use of a transverse CT image for the estimation of the dose given to the
      rectum in intracavitary brachytherapy for carcinoma of the cervix.
AB  - BACKGROUND AND PURPOSE: The three-dimensional (3D) dose distribution in
      combination with 3D anatomy of 13 patients treated for cervical carcinoma with
      intracavitary brachytherapy was analyzed. The aim of this study was to determine
      the correlation between a dose value obtained from the integral dose volume
      histogram (DVH) of the rectum and (a) the Nederlands Kanker Instituut (NKI) point
      of reference for the rectum dose (R) and (b) the highest dose to the frontal
      rectum wall in the transverse CT slice near the top of the vagina through point
      R. RESULTS: The correlation between the DVH rectum dose value for 2 cm3 in the
      highest dose region and the rectum dose at point R was poor (regression
      coefficient 0.50). On the contrary, however, the correlation between the DVH
      rectum dose value for 2 cm3 in the highest dose region and the maximum rectum
      dose value in a transverse CT slice through point R was good (regression
      coefficient 0.90). CONCLUSIONS: The maximal rectum dose value obtained from a
      transverse CT slice near the top of the vagina through point R was found to be a
      more representative point for the rectal dose burden and might therefore show a
      good correlation with complications. The point of reference for the rectal dose
      (R) was found not to be a reliable estimation of the maximal dose in the rectum.

PMID- 9632299
TI  - A preliminary comparative treatment planning study for radiotherapy of age
      related maculopathy.
AB  - PURPOSE: We present a comparative planning of different approaches for external
      radiotherapy in age-related maculopathies. MATERIALS AND METHODS: Calculated dose
      distributions and dose-volume histograms for (a) bilateral irradiation with 6 MV
      photons, (b) a single lateral-oblique beam using either photons, electrons or
      protons and (c) an anterior circular proton beam. RESULTS: For lateral photon or
      electron beams the dose to the lens is usually lower than 10% of the dose to the
      macula. The entrance doses for bilateral photon beams are about 50% which
      increase up to 100% at the orbital bone. About 5 mm of optic nerves are
      irradiated at the maximal dose while the optic chiasma is spared. A single photon
      beam gives 50% of the dose to the fellow eye. The electron beam spares the fellow
      eye but gives a rather inhomogeneous dose to the target volume. For a lateral
      proton beam, 4 mm of optic nerve receives 90% of the dose, the skin dose is at
      least 70% of the dose to the macula and the lens and the fellow eye are spared.
      An anterior proton beam gives 90% of the dose to 1 mm of optic nerve and the 50%
      isodose approaches the periphery of the lens. CONCLUSION: Doses to the critical
      structures can be dramatically diminished for all the techniques by reducing the
      beam size, but only if very precise set-up techniques are used. Proton beams are
      an attractive solution, but the impact of such a choice on the use of proton
      facilities and on the national health system should be carefully evaluated, as
      well as the risk of radio-induced secondary neoplasias.

PMID- 9632300
TI  - Focalized external radiotherapy for resected solitary brain metastasis: does the
      dogma stand?
AB  - PURPOSE: To investigate whether whole brain irradiation might be replaced by
      focalized irradiation after resection of a single brain metastasis in patients
      where extracranial tumor control is deemed to be obtained. PATIENTS AND METHODS:
      Twelve patients were introduced in a phase I/II prospective study of conformal
      postoperative external irradiation after resection of a solitary brain
      metastasis. The radiation treatment consisted of 50.4 Gy (1.8 Gy per fraction,
      five fractions per week). The planning target volume consisted of the tumor bed
      and a 2 cm safety margin. All treatments were optimized with head immobilization,
      dedicated tomodensitometry and computer assisted three-dimensional treatment
      planning. RESULTS: The median survival was 7.2 months (range 2.4-50.4 months).
      Eleven of the 12 patients died. Eight of the 12 patients presented intracranial
      recurrence and seven died as a consequence of intracranial tumor progression.
      CONCLUSIONS: Focalized external irradiation cannot serve as a reasonable
      alternative to whole brain radiotherapy (WBRT) even for patients with apparently
      one single resected brain metastasis. The dogma of 'one metastasis = multiple
      metastases' seems to be confirmed.

PMID- 9632301
TI  - Patients with brain failure who do not recover neurologically despite having no
      evidence of tumour.

PMID- 9632302
TI  - Accelerated fractionation (AF) in head and neck cancers.

PMID- 9632303
TI  - Accelerated fractionation (AF) in head and neck cancers.

PMID- 9632304
TI  - Accelerated fractionation (AF) in head and neck cancers.

PMID- 9632305
TI  - Need for caspase-2 in apoptosis of growth-factor-deprived PC12 cells.
AB  - Previous studies have shown that caspases (proteases related to interleukin-1beta
      converting enzyme) are needed for the death of trophic factor-deprived PC12
      cells. However, the protease involved in this process has not been identified.
      The results presented here strongly suggest that caspase-2 (Nedd2/Ich-1) plays a
      major role in the death of serum-deprived PC12 cells. We show that in PC12 cells
      overexpression of caspase-2 induces cell death, serum deprivation induces
      processing (i.e., activation) of the 48-kDa pro-caspase-2, and stable expression
      of caspase-2 antisense RNA inhibits apoptosis induced by serum deprivation. In
      addition, overexpression of bcl-2, which prevents this death process, also
      inhibits the processing of pro-caspase-2, suggesting that bcl-2 acts upstream of
      pro-caspase-2 activation.

PMID- 9632306
TI  - Production of paired helical filament, tau-like proteins by PC12 cells: a model
      of neurofibrillary degeneration.
AB  - Neuron-like cells derived from a rat pheochromocytoma cell line (PC12) and
      differentiated with nerve growth factor produce a paired helical filament (PHF)
      like antigen when they are subjected to heat shock (Wallace et al.: Mol Brain Res
      19:149-155, 1993). It accumulates in a localized region of the perinuclear
      cytoplasm and reacts with monoclonal antitau antibodies, which identify epitopes
      in the N- and C-terminal halves and the microtubule-binding domain of tau
      protein. The observed profile of immunoreactivity suggests the presence of full
      length and C-terminally truncated tau in a region of perinuclear cytoplasm in
      which no structurally intact PHFs could be demonstrated by conventional
      transmission electron microscopy. The accumulated tau protein colocalized with
      antibodies raised against mitochondrial outer membrane proteins and was
      associated with the presence of numerous mitochondrial profiles that were
      demonstrated with electron microscopy. Because differentiated PC12 cells
      pretreated with colcemid or Taxol prior to heat shock fail to exhibit perinuclear
      PHF-like immunoreactivity, the reported response to heat shock appears to require
      an intact system of intracellular microtubules. This PC12 system provides a model
      in which the metabolic and molecular biological underpinnings of neuronal
      degeneration in Alzheimer's disease can be manipulated. The system may eventually
      be applicable to the development of pharmaceutical agents that interfere with
      formation and/or degeneration of PHF-tau in Alzheimer's disease.

PMID- 9632307
TI  - Temporal relationships between de novo protein synthesis, calpain and caspase 3
      like protease activation, and DNA fragmentation during apoptosis in septo
      hippocampal cultures.
AB  - Caspase 3-like proteases are key executioners in mammalian apoptosis, and the
      calpain family of cysteine proteases has also been implicated as an effector of
      the apoptotic cascade. However, the influence of upstream events on
      calpain/caspase activation and the role of calpain/caspase activation on
      subsequent downstream events are poorly understood. This investigation examined
      the temporal profile of apoptosis-related events after staurosporine-induced
      apoptosis in mixed glial-neuronal septo-hippocampal cell cultures. Following 3 hr
      exposure to staurosporine (0.5 microM), calpain and caspase 3-like proteases
      processed alpha-spectrin to their signature proteolytic fragments prior to
      endonuclease-mediated DNA fragmentation (not evident until 6 hr), indicating that
      endonuclease activation is downstream from calpain/caspase activation.
      Cycloheximide, a general protein synthesis inhibitor, completely prevented
      processing of alpha-spectrin by calpains and caspase 3-like proteases, DNA
      fragmentation and cell death, indicating that de novo protein synthesis is an
      upstream event necessary for activation of calpains and caspase 3-like proteases.
      Calpain inhibitor II and the pan-caspase inhibitor Z-D-DCB each inhibited their
      respective protease-specific processing of alpha-spectrin and attenuated
      endonuclease DNA fragmentation and cell death. Thus, activation of calpains and
      caspase 3-like proteases is an early event in staurosporine-induced apoptosis,
      and synthesis of, as yet, unknown protein(s) is necessary for their activation.

PMID- 9632308
TI  - Potassium current in Drosophila neurons is increased by either dunce mutation or
      cyclic AMP.
AB  - In the Drosophila mutant dunce, short-term memory is deficient and intracellular
      cyclic adenosine monophosphate (cAMP) concentration is elevated. We examined the
      effect of increased cAMP concentration on the potassium current. The conventional
      whole-cell technique was applied to cultured "giant" Drosophila neurons derived
      from cell-division arrested embryonic neuroblasts. Potassium membrane currents
      were measured from: 1) control wild-type neurons, 2) wild-type neurons with
      dibutyryl cAMP and theophylline in the culture media for 2 days (db-cAMP
      treated), and 3) dunce neurons. Delayed-rectifier potassium current was greater
      in both dunce neurons and db-cAMP-treated wild-type neurons than in control wild
      type neurons. This result indicates that the neuronal potassium current is
      increased by the long-term increase of cAMP. Conceivably, altered neuronal
      excitability in the dunce mutant could disrupt the processing of neural signals
      necessary for learning and memory.

PMID- 9632309
TI  - Regulation of Schwann cell proliferation in cultured segments of the adult rat
      sciatic nerve.
AB  - Schwann cell proliferation was studied in cultured segments of the rat sciatic
      nerve by measurement of [3H] thymidine incorporation or through bromodeoxyuridine
      (BrdU)-labelling and immunocytochemistry. The aim was to delineate mechanisms
      involved in the injury-induced proliferative response of Schwann cells. Removal
      of extracellular Ca2+ by addition of EGTA to the culture medium suppressed [3H]
      thymidine incorporation as did the calmodulin inhibitor 48/80. The Ca2+ ionophore
      A23187 increased incorporation. Staurosporin, an inhibitor of protein kinase C
      (PKC), suppressed [3H] thymidine incorporation while phorbol-12-myristate-13
      acetate (PMA) enhanced incorporation. Manipulation of the cAMP system showed that
      increased cAMP levels inhibited proliferation. Inhibition of protein kinase A by
      HA 1004 increased the incorporation of [3H] thymidine. Immunostaining for BrdU
      and glial specific markers together with morphological evaluation of myelin
      association showed that proliferation occurred in Schwann cells. The results are
      consistent with a model in which Schwann cell proliferation is enhanced by Ca2+
      through activation of calmodulin-dependent and/or PKCdependent mechanisms.
      Inhibition is achieved through the cAMP system. Together, these results show that
      Schwann cells regulate proliferation differently in an integrated environment,
      e.g. the nerve structure, than in isolation as primary monocultures.

PMID- 9632310
TI  - Effect of hyperthermia on the transcription rate of heat-shock genes in the
      rabbit cerebellum and retina assayed by nuclear run-ons.
AB  - The induction of heat-shock protein 70 (hsp70) mRNA in the hyperthermic rabbit
      brain has been examined previously by using Northern blotting and in situ
      hybridization procedures that measure steady-state levels of mRNA, which may be
      influenced by transcript stability and transcription rate. In the present
      investigation, the in vivo transcription rate of hsp70 has been examined by using
      run-on transcription assays on isolated brain nuclei. A major up-regulation in
      the transcription rate of hsp70 was observed between 0.75 and 1.50 hours after
      hyperthermia in the cerebellum and the retina. Gel-mobility shift assays revealed
      that the time course of conversion of heat-shock transcription factor (HSF1) to a
      DNA-binding form paralleled the transcriptional induction profile of hsp70. The
      transcription rates of several nonheat-shock genes were also studied in the
      hyperthermic brain, and little change was noted relative to the induction of
      hsp70. Thus, a physiologically relevant increase in temperature of 2.5 degrees C
      induces a major up-regulation in the in vivo transcription rate of hsp70 in the
      nervous system with little affect on the transcription rates of other genes.

PMID- 9632311
TI  - Study of relapsing remitting experimental allergic encephalomyelitis SJL mouse
      model using MION-46L enhanced in vivo MRI: early histopathological correlation.
AB  - MION-46L, a superparamagnetic iron oxide contrast agent, was investigated for its
      ability to increase the sensitivity of in vivo 3D MRI in the detection of brain
      lesions in a chronic experimental allergic encephalomyelitis (crEAE) mouse model.
      Lesion conspicuity on postcontrast 3D MRI was dramatically enhanced as compared
      to precontrast images corresponding to areas of inflammatory and demyelinating
      lesions. MION-46L could be detected on Prussian blue iron stain in the vascular
      endothelium, the perivascular space, and in macrophages within perivascular cuffs
      and areas of inflammation and demyelination. By taking advantage of the MION-46L
      induced macroscopic susceptibility effect, acute early lesions measuring only 100
      microm in diameter could be detected. MION-46L enhanced MRI may be used to 1)
      provide a unique sensitivity in EAE lesion detection and correlate imaging to
      histopathology; 2) help to understand EAE lesion development and its underlying
      pathophysiology; and 3) eventually assist in preclinical screening of new
      experimental therapies directed at patients with multiple sclerosis (MS).

PMID- 9632312
TI  - Intracellular sulfatide expression in a subpopulation of astrocytes in primary
      cultures.
AB  - A highly specific antibody against sulfatide, a myelin-associated glycolipid, has
      been investigated using indirect double immunocytochemistry in rat primary
      astroglial cultures from cerebral cortex. Sulfatide was expressed in a selected
      subpopulation of astrocytes (2-3%) and was found to be exclusively located
      intracellularly. The sulfatide-positive cells appeared in two different
      morphologies: flat and stellate. Immunolabeling of the astroglial cultures showed
      that sulfatide always co-existed with GFAP or S-100, and in some cells with GD3
      (flat 90% and stellate 50%) or A2B5 (1%) antibody. The sulfatide-positive cells
      did not bind the O1 antibody, which is used as a marker for oligodendrocytes.
      Glial cultures from other regions and mixed cultures, with both neurons and glial
      cells, were examined and showed similar results. Biochemical analysis by TLC
      ELISA verified the presence of sulfatide in the astroglial culture and showed
      decreasing amounts of sulfatide with days in vitro; 0.05 nmol/mg protein at day
      10 and 0.01 nmol/mg protein at day 17. This analysis also showed that neither
      sulpholactosylceramide nor seminolipid was present, each of which also has
      affinity for the sulfatide antibody. This selective and intracellular expression
      encourages further identification of the astrocytes expressing sulfatide and the
      biological role of sulfatide in these cells.

PMID- 9632313
TI  - Syntaxin and 25-kDa synaptosomal-associated protein: differential effects of
      botulinum neurotoxins C1 and A on neuronal survival.
AB  - The Clostridium botulinum neurotoxins (BoNTs) A and C1 cleave specific proteins
      required for neuroexocytosis. We demonstrated that, in intact neurons, BoNT A
      cleaves 25-kDa synaptosomal-associated protein (SNAP-25), and BoNT C1 cleaves
      both syntaxin and SNAP-25 (Williamson et al.: Mol Biol Cell 6:61a, 1995; J Biol
      Chem 271:7694-7699, 1996). Here, we compare the actions of BoNT A and BoNT C1 on
      mature and developing mouse spinal cord neurons in cell culture and demonstrate
      that BoNT C1 is severely neurotoxic. In mature cultures, synaptic terminals
      become enlarged shortly after BoNT C1 exposure, and, subsequently, axons,
      dendrites, and cell bodies degenerate. Electron microscopy confirms that early
      degenerative changes occur in synaptic terminals when the somatic cytoplasm
      appears normal. In newly plated cultures, few neurons survive exposure to BoNT
      C1. Whereas both BoNT A and BoNT C1 cleave SNAP-25, BoNT A has no adverse effect
      on neurite outgrowth, synaptogenesis, or neuron survival. This cytotoxicity is
      unique to BoNT C1, is specific to neurons, and is initiated at the synaptic
      terminal, suggesting either a novel role for syntaxin or additional actions of
      BoNT C1. The neurodegeneration induced by BoNT C1 may be significant in terms of
      its efficacy for the clinical treatment of dystonia and spasticity.

PMID- 9632314
TI  - Thyroid hormone regulates the expression of the MAL proteolipid, a component of
      glycolipid-enriched membranes, in neonatal rat brain.
AB  - Detergent-insoluble glycosphingolipid-enriched membranes (DIGs) have been
      involved in the sorting and transport of specific proteins during oligodendrocyte
      maturation. The MAL (MAL, MVP17, VIP17) proteolipid, an integral membrane protein
      present in DIGs in mature oligodendrocytes, has been proposed as a component of
      the machinery for DIG-mediated transport in a restricted pattern of cell types
      including myelinating cells. We have previously shown that thyroid hormone
      regulates the expression of the myelin protein genes coordinately, and have
      suggested a major role for thyroid hormone in the control of oligodendrocytes
      generation. Here we show that the expression of the MAL gene is down-regulated by
      hypothyroidism and up-regulated by hyperthyroidism in myelinated regions of the
      brain. In contrast, adult-onset hypothyroidism has no effect on the steady-state
      levels of MAL mRNA. Taken together, our results show that MAL expression during
      oligodendrocyte maturation is modulated by thyroid hormone, suggesting that this
      hormone could play an important role in the myelin biogenesis during neonatal
      development.

PMID- 9632315
TI  - Influence of serotoninergic drugs on in vivo dopamine extracellular output in rat
      striatum.
AB  - In vivo microdialysis was used to investigate the mechanism behind the increase
      in extracellular dopamine (DA) induced by increase in extracellular serotonin (5
      HT) level and 5-HT1 and 5-HT2 receptor activation. The following serotoninergic
      drugs were perfused in the absence or presence of nomifensine (5 microM) or
      tetrodotoxin (TTX; 2 microM): clomipramine (10, 500 and 1,000 microM), a
      selective 5-HT reuptake inhibitor; 8-OH-DPAT (50 and 500 microM), a 5-HT1A
      receptor agonist; and alpha-methyl-5-HT (1, 5 and 50 microM), a 5-HT2 receptor
      agonist. All the serotoninergic drugs studied increased DA extracellular output
      in a dose-dependent manner. The presence of nomifensine attenuated the effect of
      perfusion of clomipramine (500 microM) and completely abolished the effect of
      perfusion of 8-OH-DPAT (500 microM) and alpha-methyl-5-HT (5 microM) on DA
      extracellular output. Clomipramine (100-1,000 microM) perfusion produced a dose
      dependent increase in DOPAC extracellular output, which was stronger when
      clomipramine (500 microM) was co-perfused with nomifensine. 8-OH-DPAT and alpha
      methyl-5-HT perfusion decreased DOPAC overflow. Addition of TTX to the perfusion
      fluid one hour before serotoninergic drugs perfusion, did not completely abolish
      the effect on dopamine extracellular output produced by the serotoninergic drugs.
      These data seem to indicate that increase in extracellular 5-HT level and 5-HT1
      and 5-HT2 receptor activation increase in vivo DA extracellular output in the
      striatum mainly by a nonexocytotic mechanism involving DA uptake sites and,
      secondarily, by activation of 5-HT receptors.

PMID- 9632316
TI  - Glutamate modulation of dendrite outgrowth: alterations in the distribution of
      dendritic microtubules.
AB  - Glutamate can both facilitate and inhibit dendrite outgrowth in vitro. The major
      effects of low levels of glutamate occur only on the dendrites (not the axon) of
      pyramidal neurons and may be important for modulating dendrite outgrowth during
      neuronal development in vivo. Cytoskeletal changes resulting from glutamate
      exposure must underlie these changes in dendrite outgrowth. In the present study,
      hippocampal neuron cultures were used to measure the outgrowth of both axons and
      immature dendrites in the presence or absence of 50 microM glutamate.
      Subsequently, neurons were extracted and fixed for immunofluorescent labeling of
      microtubules and rhodamine phalloidin labeling of microfilaments. Additionally,
      neurons were prepared for electron microscopy to examine dendritic microtubules
      at the ultrastructural level. Glutamate led to increased dendrite outgrowth in
      the short term (4 hr) and dendrite retraction in the long term (8 hr). After
      short-term glutamate exposures, no obvious morphological changes occur in either
      the microtubules or microfilaments. However, longer glutamate exposure causes a
      decrease in the number of microtubules in the distal region of retracting
      dendrites, and causes an increase in microtubule number in the dendritic shaft of
      both retracting and growing dendrites. Thus, the microtubule cytoskeleton may be
      involved in producing the changes in dendrite outgrowth caused by glutamate
      exposure.

PMID- 9632317
TI  - Endogenous voltage-gated potassium channels in human embryonic kidney (HEK293)
      cells.
AB  - Endogenous voltage-gated potassium currents were investigated in human embryonic
      kidney (HEK293) and Chinese hamster ovary (CHO) cells using whole-cell voltage
      clamp recording. Depolarizing voltage steps from -70 mV triggered an outwardly
      rectified current in nontransfected HEK293 cells. This current had an amplitude
      of 296 pA at +40 mV and a current density of 19.2 pA/pF. The outward current was
      eliminated by replacing internal K+ with Cs+ and suppressed by the K+ channel
      blockers tetraethylammonium and 4-aminopyridine. Raising external K+ attenuated
      the outward current and shifted the reversal potential towards positive
      potentials as predicted by the Nernst equation. The current had a fast activation
      phase but inactivated slowly. These features implicate delayed rectifier (I(K))
      like channels as mediators of the observed current, which was comparable in size
      to I(K) currents in many other cells. A small native inward rectifier current but
      no transient outward current I(A), the M current I(M), or Ca2+-dependent K+
      currents were detected in HEK293 cells. In contrast to these findings in HEK293
      cells, little or no I(K)-like current was detected in CHO cells. The difference
      in endogenous voltage-activated currents in HEK293 and CHO cells suggest that CHO
      cell lines are a preferred system for exogenous K+ channel expression.

PMID- 9632318
TI  - Presenilin-1 mutation alters NGF-induced neurite outgrowth, calcium homeostasis,
      and transcription factor (AP-1) activation in PC12 cells.
AB  - Mutations in the presenilin-1 (PS-1) gene are responsible for many cases of
      autosomal dominant early-onset inherited Alzheimer's disease (AD). PS-1 is
      expressed in neurons where it is localized primarily to the endoplasmic reticulum
      (ER); the normal function of PS-1 and its pathogenic mechanism in AD are not
      known. We now report that expression of an AD-linked human PS-1 mutation (L286V)
      in PC12 cells results in aberrant differentiation responses to nerve growth
      factor (NGF). The extent of neurite outgrowth during a 10-day period of exposure
      to NGF was significantly reduced in lines stably expressing mutant PS-1. NGF
      induced a prolonged elevation of intracellular calcium levels which was
      significantly enhanced in cells expressing mutant PS-1. Induction of DNA binding
      activity of the transcription factor AP-1 by NGF was markedly suppressed in cells
      expressing mutant PS-1. Collectively, these findings demonstrate that a PS-1
      mutation alters cellular signaling systems associated with NGF-induced
      differentiation in PC12 cells. Altered responsivity to neurotrophic factors could
      play a role in the pathogenesis of neuritic degeneration and cell death in human
      carriers of PS-1 mutations.

PMID- 9632319
TI  - Exercise training and chronic obstructive pulmonary disease: past and future
      research directions.
AB  - Chronic obstructive pulmonary disease (COPD) is a major cause of death and
      disability in the United States. It is characterized by symptoms of
      breathlessness that result in sedentary lifestyle, physical deconditioning, and
      reduced quality of life. Previous research has shown that exercise training in
      patients with COPD will improve physical function and may help improve the
      quality of life. Unfortunately, the majority of these previous studies have not
      been pursued with adequate scientific rigor and the conclusions regarding the
      efficacy of exercise as an adjunct in the treatment of COPD are equivocal. The
      purpose of this article is to review the previous research that has focused on
      the effects of exercise training on individuals with COPD, to examine the
      problems with this previous research, and to emphasize the need and identify
      topics for further outcome-based research.

PMID- 9632320
TI  - Predictors of outpatient cardiac rehabilitation utilization: the Minnesota Heart
      Surgery Registry.
AB  - BACKGROUND: A significant proportion of eligible patients do not participate in
      cardiac rehabilitation. The purpose of this study was to document patterns of
      outpatient cardiac rehabilitation use and identify factors predicting its use.
      METHODS: The Acute Myocardial Infarction Registry of the Minnesota Heart Survey
      enrolled 3,841 patients admitted on suspicion of acute myocardial infarction (MI)
      to the coronary care units at six Minneapolis-St. Paul metropolitan hospitals.
      Participants were contacted 1 year after index hospitalization and asked if they
      participated in cardiac rehabilitation since discharge. RESULTS: Among those
      discharged with a MI, 47% participated in outpatient cardiac rehabilitation or an
      exercise program at an exercise facility, home, or both during the 1-year follow
      up period. Among those discharged with angina, 21% attended cardiac
      rehabilitation. Usage increased when cardiac revascularization procedures were
      performed during the index hospitalization. Women with an angina or MI diagnosis
      were significantly less likely to use cardiac rehabilitation than men. Older
      patients were also less likely to use rehabilitation, with gender difference
      persisting across age strata. As education increased, cardiac rehabilitation
      utilization increased. Those not employed were less likely to use cardiac
      rehabilitation services. The strongest independent predictors of cardiac
      rehabilitation utilization were age and revascularization procedures (coronary
      artery bypass grafting or coronary angioplasty), simultaneously adjusting for
      demographic information, and cardiovascular disease risk factors. CONCLUSIONS:
      These data suggest that there is a disparity in cardiac rehabilitation
      utilization with lower rates among women, older individuals, those with less
      education, and the unemployed.

PMID- 9632321
TI  - The acceptable risk of driving after myocardial infarction: are bus drivers a
      special case?
AB  - BACKGROUND: Bus drivers frequently encounter difficulty in returning to their
      former employment after recovery from myocardial infarction. The risk that a
      recurrence of myocardial infarction may cause a personal-injury accident is
      analyzed. METHODS: The Cumulative Medical Index and Current Contents was searched
      systematically from 1980 to date, accepting papers irrespective of language.
      Relevant earlier material was drawn from the author's published reviews on bus
      driving and myocardial infarction and vehicle accidents. One hundred twenty-three
      articles were included in the database, of which 110 were used in the review.
      RESULTS: The risk of a personal injury accident or fatality from a sudden
      cardiovascular incident is calculated as the product of typical driving time per
      day (Td = 0.167), vehicle characteristics (V) (a low factor of 0.167 for an urban
      bus because of slow speed and use of reserved curb lanes), the risk of recurrence
      of a sudden cardiovascular incident (SCI) (.015, somewhat greater in bus drivers
      than in the general population), and the risk that such an incident will cause a
      personal-injury accident (Ac) (at 0.005, probably lower than in the general
      population because of low vehicle speeds and the bus driver's experience in
      defensive driving). CONCLUSIONS: The overall risk is 0.00002, 1 in 50,000 driver
      years, is lower than accepted for passenger-car operators, and only slightly
      greater than for the older symptom-free adult. Bus drivers who meet the current
      standards of the Canadian Cardiovascular Society should be encouraged to return
      to their former employment.

PMID- 9632322
TI  - On-site evaluation of bus drivers with coronary heart disease.
AB  - BACKGROUND: Bus drivers with ischemic heart disease have been denied normal
      employment, although they satisfy Canadian Cardiovascular Society (CCS)
      Guidelines. To show the safety of their reemployment, we compared their responses
      when driving buses with those seen during graded exercise testing. METHODS:
      Twenty-two male city bus drivers, aged 48.1 +/- 5.6 years (19 had a myocardial
      infarction, 2 had coronary artery bypass graft, 1 had documented ischemic heart
      disease) were referred for work evaluation. After a CCS cardiopulmonary exercise
      test, they were accompanied by a physician and a therapist/technician on a normal
      shift. Note was kept of symptoms, signs, electrocardiogram (telemetry), blood
      pressure (ambulatory recording unit), and Borg rating of effort throughout.
      RESULTS: Average values for peak heart rate (101 +/- 12.5 versus 148.2 +/- 17.2
      beats/min), peak systolic pressure (150.0 +/- 20.8 versus 198.9 +/- 25.7 mm Hg),
      peak rate-pressure product (15,259 +/- 3,369 versus 29,500 +/- 5,283 units), peak
      Borg RPE (9.9 +/- 1.4 versus 17.4 +/- 3.0 units), and peak ST-segmental
      depression (-0.03 +/- 0.07 versus -0.07 +/- 0.09 mV) during the shift were only
      about a half of average values reached during the graded stress test. Moreover,
      peak values were reached at the end of the shift, when carrying the loaded fare
      box, rather than when driving. CONCLUSIONS: Cardiovascular strain during bus
      driving is much less than during the CCS stress test for drivers. Using CCS
      methodology, the risk that a sudden cardiovascular incident will cause injury or
      death of others in the first year after recovery from myocardial infarction is
      estimated at 1 in 50,000 driver-years. Thus, those satisfying CCS requirements
      can return to full driving duties promptly, with minimal risk to themselves,
      passengers, or other road users.

PMID- 9632323
TI  - Clinical workload decreases the level of aerobic fitness in housestaff
      physicians.
AB  - PURPOSE: To examine the relationship between clinical workload and aerobic
      fitness. METHODS: Twenty healthy intern and resident volunteers were studied in a
      cross over manner to compare their aerobic fitness after a 1 month "easy"
      clinical rotation (ECR) to that after a 1 month "hard" clinical rotation (HCR).
      The ECR and HCR were prospectively estimated as requiring <60 (ECR) and >70 (HCR)
      total hours per week of hospital work respectively. Aerobic fitness was
      determined by directly measuring peak oxygen uptake (peakVO2) during peak cycle
      exercise testing after each rotation. Clinical workload for the month preceding
      the exercise test was estimated by documenting the amount of hospital work and
      sleep lost because of on-call duties. The average weekly amount of effective
      aerobic training for each rotation was also documented. RESULTS: Trainees had a
      206.4 (P = 0.0019, 95% CI 94-318.8) mL/min or 3 mL/kg/min (P = 0.0019, 95% CI 1.5
      4.4) improvement of peakVO2 after the ECR compared with the HCR. Trainees
      averaged 1 (95% CI 0.16-1.81) less hour per week of exercise training, 34.1 more
      hours per week of hospital work (95% CI 23.0-45.3, P < 0.0001) and lost 19.1
      hours more sleep per month (95% CI 11.8-26.4, p < 0.0001) during the HCR compared
      with the ECR. There was no correlation between changes in peakVO2 and changes in
      exercise training between the two rotations. CONCLUSION: Clinical workload seems
      to adversely affect aerobic fitness independent of changes in exercise training.
      This supports previous less-objective survey data.

PMID- 9632324
TI  - Validity of body composition assessment methods for older men with cardiac
      disease.
AB  - PURPOSE: This study was designed to determine which of several body composition
      assessment methods was most accurate for patients with cardiac disease for the
      purpose of outcome measurement. METHODS: Six body composition assessment methods
      were administered to each of 24 men with cardiac disease. Methods included
      circumference measurement, skinfold measurement, near-infrared interactance via
      the Futrex-5000, bioelectrical impedance via the BioAnalogics ElectroLipoGraph
      and Tanita TBF-150, and hydrostatic weighing, the criterion measure. RESULTS: A
      repeated measures analysis of variance indicated no significant (P > .05)
      difference between circumference and skinfold measurements compared to
      hydrostatic weighing. Near-infrared interactance presented the best standard
      error of estimates (3.5%) and the best correlation (r = .84) with hydrostatic
      weighing; however, the constant error was 3.76%. Bioelectrical impedance measured
      by the ElectroLipoGraph and TBF-150 instruments significantly underestimated
      percent body fat by 8.81% and 4.8%, respectively. CONCLUSIONS: In this study of
      middle-aged to older men with cardiac disease, the best method for determining
      body fat was circumferences. This technique was accurate, easy to administer,
      inexpensive, and had a lower error potential than the other techniques. Skinfold
      measurements were also closely related to hydrostatic weighing, but should be
      performed only by experienced practitioners because there is a greater potential
      for tester error in certain patients. In the future, near-infrared interactance
      measurements may be a viable technique for body composition assessment in
      patients with cardiac disease. However, algorithms specific to the population of
      patients with cardiac disease being tested must be developed before this
      technique can be routinely recommended for body composition assessment.
      Bioelectrical impedance assessment by either method is not recommended for
      patients with cardiac disease, as it consistently underestimated percent body fat
      when compared to hydrostatic weighing in this population.

PMID- 9632325
TI  - Effects of music on exercise and perceived symptoms in patients with chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: The purpose of this study was to examine the effects of music on
      exercise tolerance and perceived symptoms during treadmill walking in patients
      with chronic obstructive pulmonary disease (COPD). METHODS: Nineteen patients
      with COPD recruited from a pulmonary rehabilitation program participated in
      treadmill walking sessions on three separate days. The first session consisted of
      a practice walk. The second and third walking sessions were 6-minute timed tests
      in which the subjects were asked to walk as fast as possible under two
      conditions: a control walk and a music walk. Subjective assessments of perceived
      dyspnea and effort were obtained during the walks by the modified Borg scale.
      RESULTS: Distances walked were 331m +/- 19 (SE) for the music walk and 321m +/-
      21 (SE) for the control walk (P = .25). Within each condition, ratings of
      perceived exertion and dyspnea increased from minute 1 to minute 6 (P < 0.05).
      CONCLUSION: There were no statistically significant differences observed between
      treatment conditions for distance walked, perceived dyspnea or ratings of
      perceived exertion. It should be noted that 60% of the subjects voluntarily
      commented that they enjoyed listening to music while they exercised.

PMID- 9632326
TI  - The application of interval training for exercise prescription in cardiac
      rehabilitation.

PMID- 9632327
TI  - A retrospective analysis of lingual nerve sensory changes after mandibular
      bilateral sagittal split osteotomy.
AB  - PURPOSE: The purpose of this retrospective study was to determine the patient
      reported incidence, duration, and perceived deficit in daily activities
      associated with lingual nerve (LN) sensory changes after bilateral sagittal split
      osteotomy (BSSO) of the mandible and to compare them with inferior alveolar nerve
      (IAN) sensory changes in the same study population. MATERIALS AND METHODS:
      Questionnaires were mailed to 316 patients who had undergone BSSO procedures
      between 1980 and 1993. The patients were queried for perceived sensory changes in
      the distribution of the IAN and LN; duration of these sensory changes; and
      alteration in daily activities caused by these sensory changes. The same
      questionnaire was mailed to 47 patients who had undergone isolated genioplasty
      (GP) to control for the normal variance of non-BSSO surgery on perceived LN
      sensory changes. RESULTS: Forty-three percent of the BSSO patients and 38% of the
      GP patients returned the questionnaires. Within the BSSO group, 19.4% reported LN
      sensory changes, of which 69.3% reported that these changes resolved within 1
      year; 88% reported altered daily activities. By comparison, 95.5% reported a
      perceived IAN sensory change, of which 27.3% reported that these changes resolved
      within 1 year; 57% reported altered daily activities. Within the GP control
      group, 11% reported LN sensory changes; none of the reported sensory changes
      lasted longer than 1 month. CONCLUSIONS: A small percentage of patients report LN
      sensory changes after BSSO. When compared with IAN reported sensory changes, LN
      sensory changes resolve more frequently and sooner, but they are associated with
      greater perceived deficits in daily activity. The interpretation of the reported
      incidence of LN change must be critically reviewed because control subjects also
      responded positively.

PMID- 9632328
TI  - Bone maintenance 5 to 10 years after sinus grafting.
AB  - PURPOSE: This radiographic study determined the amount of bone around
      hydroxyapatite (HA)-coated dental implants that were placed into bone-grafted
      maxillary sinuses. PATIENTS AND METHODS: Postoperative complex motion tomograms
      using the Grossman technique were taken on 16 patients who had 27 maxillary sinus
      grafts performed using particulate autogenous iliac bone with and without
      demineralized bone, autogenous iliac corticocancellous block with and without
      demineralized bone, and autogenous jaw bone with demineralized bone. Bone levels
      were measured from the new floor of the grafted sinus to the apex of the implant
      and to the alveolar crest. The resulting bone level measures were compared with
      the type of graft used. All patients had been restored for 5 to 10 years after
      simultaneous graft and implant placement. RESULTS: For all patients summed
      together, the average amount of bone from the top of the graft to the apex of the
      implant was 3.3 +/- 3.1 mm, and the average amount of bone from the top of the
      graft to the alveolar crest was 17.6 +/- 3.1 mm. The average level of bone in the
      sinuses of patients grafted with autogenous iliac bone was greater than the
      average level of bone in those grafted with autogenous bone combined with
      demineralized bone. CONCLUSION: The results of this study indicate that
      autogenous bone grafts are maintained in the maxillary sinus, but the results
      with autogenous bone alone are better than when demineralized bone is added.
      However, this difference may not be clinically significant.

PMID- 9632329
TI  - Use of the tongue flap for intraoral reconstruction: a report of 16 cases.
AB  - PURPOSE: This article reports the authors' experience with the use of the tongue
      flap for intraoral soft tissue reconstruction. PATIENTS AND METHODS: From May
      1992 to December 1996, 16 patients were treated with a tongue flap for
      reconstruction of a variety of intraoral soft tissue defects. Ages ranged from 16
      to 65 years with a mean of 39.6 years. RESULTS: The procedure was successful in
      15 patients. There were six complications: one total necrosis, four partial
      necroses, and one infection. Partial necrosis and infection were well controlled
      by conservative treatment. CONCLUSION: Use of the tongue flap is a versatile
      method for reconstruction of a variety of intraoral soft tissue defects.

PMID- 9632330
TI  - Lip augmentation using an alloderm graft.
AB  - A wide variety of surgical procedures and implant materials have been used to
      satisfy the growing demand of patients for lip augmentation. The authors describe
      our experience with Alloderm (LifeCell Corp, The Woodlands, TX). It has proven to
      be a safe and effective means of offering mild to moderate augmentation of the
      lips.

PMID- 9632331
TI  - Changes in nasal tip projection and rotation after septorhinoplasty: a
      cephalometric analysis.
AB  - PURPOSE: This prospective study reports on changes in nasal tip projection and
      nasal tip rotation before and after septorhinoplasty analyzed cephalometrically.
      PATIENTS AND METHODS: Forty patients undergoing primary septorhinoplasty were
      studied prospectively. Lateral cephalometric radiographs taken in the natural
      head position were obtained before and 6 to 45 months (mean, 17.1) after surgery.
      In 10 patients, serial radiographs were taken at 6 and 12 months, and in seven
      patients they were taken at 12 and 24 months after surgery. Nasal tip projection
      (NTP) was defined as the distance between articulare (Ar) and pronasion (PRN).
      Nasal tip rotation (NTR) was defined as the change in the angle (N-Ar-PRN) after
      surgery. A surgical goal to increase, decrease, or maintain NTP and NTR was
      assigned to each patient before surgery. RESULTS: NTP changed in the desired
      direction in 16 of 40 patients (40%). NTR changed in the desired direction in 25
      of 40 patients (63%). In the patients studied serially, NTP decreased an average
      0.7 mm between 6 and 12 months (P = .018), and 0.6 mm between 12 and 24 months (P
      = .071). CONCLUSIONS: Decreased NTP and NTR were the most easily achieved
      surgical objectives. Maintaining or increasing NTP is less predictable.
      Typically, there is a progressive loss of NTP after surgery independent of the
      surgical goal. Cephalometric analysis is a useful tool to measure changes in NTP
      and NTR after septorhinoplasty.

PMID- 9632332
TI  - Simultaneous malaroplasty with porous polyethylene implants and orthognathic
      surgery for correction of malar deficiency.
AB  - PURPOSE: Patients with skeletal malrelationships caused by maxillary
      anteroposterior defect and midface hypoplasia may present with an alteration of
      cheekbone contour. High osteotomies, segmental osteotomies of the zygomatic
      complex, and malar expansion with alloplastic materials can be performed to
      improve facial aesthetics. This article describes the restoration of cheekbone
      nasal base-lip contour by performing a malaroplasty using an alloplastic implant
      in addition to orthognathic surgery. PATIENTS AND METHODS: From 1995 to 1996, 17
      patients with maxillomandibular malrelationships and deficient cheekbone contour
      were tested by malar augmentation with porous high-density polyethylene in
      association with maxillary advancement and mandibular setback. The diagnosis of
      cheekbone contour alteration was made after observing the patient from a lateral,
      frontal, and oblique point of view. The position of the implant was determined by
      using Mladick's point, with lateral or medial extension in relation to the
      depressed area. RESULTS: By the restoration of normal cheekbone-nasal base-upper
      lip contour produced excellent aesthetic results in all patients. CONCLUSIONS:
      Malaroplasty in association with bimaxillary orthognathic surgery seems to be an
      effective procedure for treating midface skeletal deficiencies.

PMID- 9632333
TI  - In vitro analysis of the accuracy of subtraction radiography and computed
      tomography scanning for determination of bone graft volume.
AB  - PURPOSE: This study evaluated the accuracy of digital subtraction radiography
      (DSR) and three-dimensional computed tomography (3D CT) for determination of bone
      graft volume in the maxillofacial region. MATERIALS AND METHODS: Standardized
      bone defects were made on the top of the alveolar ridge in 10 dry pig mandibles.
      To resemble the clinical situation, a bone block was harvested from the
      symphyseal region of the mandible and fixed in the defect. True bone graft volume
      was determined by the water displacement technique (VOL I) and correlated to
      direct measurements by calipers (VOL II). The mean gray value of the bone graft
      as imaged by DSR was correlated to the directly measured thickness. Furthermore,
      VOL I was correlated to the 3D CT of the bone graft (VOL III) and to the 3D CT
      with the bone graft fixed in the defect (VOL IV). RESULTS: There was a strong
      correlation between VOL I and VOL II (r = .95), whereas there was a poorer
      correlation between mean gray level in DSR and measured bone thickness (r = .63).
      A strong correlation was also registered between VOL I and VOL III (r = .97) and
      VOL I and VOL IV (r = .97).

PMID- 9632334
TI  - An experimental investigation of the safe distance for internal orbital
      dissection.
AB  - PURPOSE: The purpose of this investigation was to determine the distance from the
      orbital rim to the important soft tissues of the orbital apex using eight
      reference points to provide clinically useful information for surgical decision
      making. MATERIALS AND METHODS: Eight human cadavers were used in this
      investigation. After circumorbital incisions were made and the canthal ligaments
      were detached, a careful subperiosteal dissection was performed to the soft
      tissues of the orbital apex. Four reference lines were established. The first two
      were based on a horizontal line drawn through the medial and lateral canthal
      ligaments and a perpendicular to this through the infraorbital foramen. The other
      two were created at points 45 degrees from the first two. Depth measurements were
      made with a straight probe at the eight points where the lines crossed the
      orbital rim. Means, standard deviations, and ranges were derived, and statistical
      differences were calculated between right and left orbits using a paired-samples
      t-test. Because no right and left differences were noted (P < .05), the data were
      pooled. RESULTS: The mean distance from the orbital rim to the soft tissues of
      the orbital apex was 44.1 +/- 1.4 mm medially, 38.3 +/- 3.0 mm laterally, 44.5 +/
      1.72 superiorly, and 39.4 +/- 2.9 mm inferiorly. The superomedial distance was
      46.3 +/- 2.7 mm, the inferomedial distance was 44.1 +/- 1.4 mm, the inferolateral
      distance was 41.4 +/- 2.5 mm, and superolateral distance was 39.4 +/- 2.8 mm.
      CONCLUSIONS: The distances from the orbital rim to the soft tissues of the
      orbital apex varied among the eight different reference points (range, 38.3 +/-
      3.0 mm to 46.3 +/- 2.7 mm). No distance was less than 31.0 mm or exceeded 51.1
      mm. There was no difference noted (P < .05) between the right and left sides for
      each of the corresponding reference points.

PMID- 9632335
TI  - Morphologic changes in the elastic fibers of the temporomandibular joint after
      experimental disc perforation in the rabbit.
AB  - PURPOSE: Elastic fibers in the attachment regions of the temporomandibular joint
      (TMJ) are considered important in the movements of the disc during jaw motion.
      This study was designed to determine whether there are change in the elastic
      fibers of the TMJ when the disc is perforated for a long period. MATERIALS AND
      METHODS: Each TMJ of five rabbits was surgically exposed, and a mediolateral
      perforation was made in the center of the articulating region of the disc with a
      scalpel. Five untreated and three sham-operated rabbits were used as controls.
      The TMJs were removed after 10 months and processed for histochemical
      demonstration of elastic fibers. RESULTS: Osteoarthritic changes and a
      significant decrease in number of the elastic fibers in the anterior-inferior
      attachment and posterior-inferior attachment of the TMJ disc were observed after
      disc perforation. Conversely, elastic fibers appeared in the fibrous tissue on
      the resorbed bone of the articular eminence. CONCLUSIONS: Experimental disc
      perforation changes the distribution and density of the elastic fiber in the TMJ
      as well as causes osteoarthritis. A knowledge of these facts may improve our
      understanding of perforation of the disc.

PMID- 9632336
TI  - Right facial edema associated with localized gingival swelling.

PMID- 9632337
TI  - Unilateral dysplasia of the mandibular condyle: report of a case.

PMID- 9632338
TI  - A case of maxillary and zygomatic duplication.

PMID- 9632339
TI  - The use of preoperative percutaneous transcatheter vascular occlusive therapy in
      the management of Sturge-Weber syndrome: report of a case.

PMID- 9632340
TI  - Concurrent cementifying and ossifying fibromas of the mandible: report of a case.

PMID- 9632341
TI  - Desmoplastic ameloblastoma in the maxilla: a case report.

PMID- 9632342
TI  - Central odontogenic granular cell tumor: immunohistochemical study of two cases.

PMID- 9632343
TI  - Resection of the anterior mandible and reconstruction with a microvascular graft
      via an intraoral approach: a report of two cases.

PMID- 9632344
TI  - A technique to improve positioning of the transmandibular posts of the
      transmandibular implant.

PMID- 9632345
TI  - Calvarial bone graft harvest using the Gigli saw.

PMID- 9632346
TI  - Peer review of advertising.

PMID- 9632347
TI  - The role of distraction osteogenesis in oral and maxillofacial surgery.

PMID- 9632348
TI  - Spiro[1H-indene-1,4'-piperidine] derivatives as potent and selective non-peptide
      human somatostatin receptor subtype 2 (sst2) agonists.

PMID- 9632349
TI  - Isochroman-6-carboxamides as highly selective 5-HT1D agonists: potential new
      treatment for migraine without cardiovascular side effects.

PMID- 9632350
TI  - Inhibition of in vitro and in vivo HIV replication by a distamycin analogue that
      interferes with chemokine receptor function: a candidate for chemotherapeutic and
      microbicidal application.
AB  - Select chemokine receptors act as coreceptors for HIV-1 entry into human cells
      and represent targets for antiviral therapy. In this report we describe a
      distamycin analogue, 2,2'-[4, 4'-[[aminocarbonyl]amino]bis[N,4'-di[pryrrole-2
      carboxamide- 1, 1'-dimethyl]]-6,8-naphthalenedisulfonic acid]hexasodium salt (NSC
      651016), that selectively inhibited chemokine binding to CCR5, CCR3, CCR1, and
      CXCR4, but not to CXCR2 or CCR2b, and blocked chemokine-induced calcium flux.
      Inhibition was not due to nonspecific charge interactions at the cell surface,
      but was based on a specific competition for the ligand receptor interaction sites
      since the inhibitory effect was specific for some but not all chemoattractant
      receptors. NSC 651016 inhibited in vitro replication of a wide range of HIV-1
      isolates, as well as HIV-2 and SIV, and exhibited in vivo anti-HIV-1 activity in
      a murine model. In contrast, a distamycin analogue with similar structure and
      charge and the monomeric form of NSC 651016 demonstrated no inhibitory effects.
      These data demonstrate that molecules which interfere with HIV-1 entry into cells
      by targeting specific chemokine coreceptors can provide a viable approach to anti
      HIV-1 therapy. NSC 651016 represents an attractive candidate for the
      chemotherapeutic treatment of HIV-1 infection and as a microbicide to prevent the
      sexual transmisssion of HIV-1. Moreover, NSC 651016 can serve as a template for
      medicinal chemical modifications leading to more effective antivirals.

PMID- 9632351
TI  - Rational design and combinatorial evaluation of enzyme inhibitor scaffolds:
      identification of novel inhibitors of matrix metalloproteinases.
AB  - The discovery of a novel series of heterocyclic matrix metalloproteinase (MMPs)
      inhibitors is described. Published crystal structures of peptidyl hydroxamates
      bound to MMPs were the basis for the rational design of diketopiperazine (DKP)
      inhibitors. Combinatorial libraries were prepared and evaluated for their ability
      to inhibit collagenase-1, stromelysin-1, and gelatinase-B substrate hydrolysis.
      Deconvolution of active pools resulted in the identification of potent inhibitors
      (IC50's < 100 nM) of collagenase-1 and gelatinase-B, with the most potent
      inhibitor exhibiting an IC50 of 30 nM against collagenase-1. A description of the
      combinatorial evaluation process, as well as initial SAR interpretation for this
      novel series, is provided.

PMID- 9632352
TI  - A pyridoxine cyclic phosphate and its 6-azoaryl derivative selectively potentiate
      and antagonize activation of P2X1 receptors.
AB  - Analogues of the P2 receptor antagonists pyridoxal-5'-phosphate and the 6
      azophenyl-2',4'-disulfonate derivative (PPADS), in which the phosphate group was
      cyclized by esterification to a CH2OH group at the 4-position, were synthesized.
      The cyclic pyridoxine-alpha4, 5-monophosphate, compound 2 (MRS 2219), was found
      to be a selective potentiator of ATP-evoked responses at rat P2X1 receptors with
      an EC50 value of 5.9 +/- 1.8 microM, while the corresponding 6-azophenyl-2',5'
      disulfonate derivative, compound 3 (MRS 2220), was a selective antagonist. The
      potency of compound 3 at the recombinant P2X1 receptor (IC50 10.2 +/- 2.6 microM)
      was lower than PPADS (IC50 98.5 +/- 5.5 nM) or iso-PPADS (IC50 42.5 +/- 17.5 nM),
      although unlike PPADS its effect was reversible with washout and surmountable.
      Compound 3 showed weak antagonistic activity at the rat P2X3 receptor (IC50 58.3
      +/- 0.1 microM), while at recombinant rat P2X2 and P2X4 receptors no enhancing or
      antagonistic properties were evident. Compounds 2 and 3 were found to be inactive
      as either agonists or antagonists at the phospholipase C-coupled P2Y1 receptor of
      turkey erythrocytes, at recombinant human P2Y2 and P2Y4 receptors, and at
      recombinant rat P2Y6 receptors. Similarly, compounds 2 and 3 did not have
      measurable affinity at adenosine A1, A2A, or A3 receptors. The lack of an
      aldehyde group in these derivatives indicates that Schiff's base formation with
      the P2X1 receptor is not necessarily required for recognition of pyridoxal
      phosphate derivatives. Thus, compounds 2 and 3 are relatively selective
      pharmacological probes of P2X1 receptors, filling a long-standing need in the P2
      receptor field, and are also important lead compounds for future studies.

PMID- 9632353
TI  - Synthesis and characterization of long chain alkyl acyl carnitine esters.
      Potentially biodegradable cationic lipids for use in gene delivery.
AB  - A series of alkyl acyl carnitine esters (alkyl 3-acyloxy-4-trimethylammonium
      butyrate chloride) were synthesized as potential biocompatible cationic lipids
      for use in gene transfer. The physicochemical properties of the lipids, liposomes
      prepared from them, and their complexes with DNA were characterized by
      differential scanning calorimetry (DSC), particle size, zeta potential, and
      surface monolayer measurements. The transition temperatures and behavior at an
      air-water interface for this series are similar to phosphatidylcholines with the
      same hydrocarbon chain length. The physical properties of the l derivatives were
      not significantly different from the dl derivatives. At 70 degrees C, the acyl
      chains were readily hydrolyzed at pH 7. The influence of the aliphatic chain
      length (n = 12-18) on transfection efficiency in vitro was determined using
      cationic liposomes prepared from these lipids or their mixtures with the helper
      lipids, dioleoylphosphatidylethanolamine (DOPE), dioleoylphosphatidylcholine,
      monooleoylglycerol, and cholesterol (Chol). The mixture of myristyl 3
      myristoyloxy-4-trimethylammonium butyrate chloride (MMCE, 4d) with DOPE at a 1:1
      molar ratio mediated the highest transfection efficiency in cell culture. The
      mixture of oleyl 3-oleoyloxy-4-trimethylammonium butyrate chloride (OOCE, 4f)
      with Chol at a 1:1 molar ratio gave the highest transfection efficiency after
      intravenous administration in mice. In vivo gene expression using 4f was
      comparable to values obtained with the best cationic lipids reported to date.

PMID- 9632354
TI  - Molecular modeling studies of the DNA-topoisomerase I ternary cleavable complex
      with camptothecin.
AB  - The present studies provide a three-dimensional model for the postulated ternary
      cleavable complex of topoisomerase I (top1), DNA, and camptothecin (CPT).
      Molecular simulations were done using the AMBER force field. The results suggest
      that a ternary cleavable complex might be stabilized by several hydrogen bonds in
      the binding site. In this proposed "drug-stacking" model, CPT is
      pseudointercalated in the top1-linked DNA cleavage site and interacts with the
      protein near its catalytic tyrosine through hydrogen bonding and stacking. The
      structural model is consistent with the following experimental observations: (i)
      the N3 position of the 5' terminal purine of the cleaved DNA strand is readily
      alkylated by 7-chloromethyl 10,11-methylenedioxy CPT; (ii) CPT generally
      tolerates substituents at positions 7, 9, and 10 but is inactivated by additions
      at position 12; (iii) 10,11-methylenedioxy (MDO) CPT is much more potent than
      10,11-dimethoxy (DMO) CPT; (iv) the lactone portion of CPT is essential for top1
      inhibitory activity; (v) 20S derivatives of CPT are much more potent than the 20R
      analogues; (vi) a catalytic tyrosine hydroxyl in top1 covalently links to the 3'
      terminal base, T, of the cleaved DNA strand; and (vii) top1 mutation Asn722Ser
      leads to CPT resistance. A total of 18 camptothecin derivatives with different
      DNA cleavage potencies were docked into the hypothetical cleavable complex
      binding site to test and refine the model. These studies provide insight into a
      possible mechanism of top1 inhibition by CPT derivatives and suggest rational
      approaches for the design of new CPT derivatives.

PMID- 9632355
TI  - L-carnitine esters as "soft", broad-spectrum antimicrobial amphiphiles.
AB  - A new class of antimicrobial, "soft", quaternary ammonium l-carnitine esters, of
      the type (CH3)3N+-CH2-CHOCO(R1)-CH2-COO(R2) Cl-, has been designed, with R1 and
      R2 being in general long-chain alkyl substituents. The series shows good activity
      against a wide range of bacteria, yeasts, and fungi. Lipophilicity has been
      measured by RP-HPLC method to give the logarithm of the experimental capacity
      factor (log k'), and a quantitative relationship has been determined between log
      k' and the theoretical partition coefficient (CLOGP); also, bond-dipole
      descriptors have been introduced into calculations by accounting for polar
      moieties present within the apolar cores of the molecules, giving a more refined
      calculated capacity factor (log k'calcd). Finally the latter has been related to
      the antimicrobial activity (MIC values). The proposed models are predictive for
      the best broad-spectrum antimicrobial compound within the series.

PMID- 9632356
TI  - N2- and C8-substituted oligodeoxynucleotides with enhanced thrombin inhibitory
      activity in vitro and in vivo.
AB  - 2'-Deoxyguanosine (G) analogues carrying various hydrophobic substituents in the
      N2 and C8 positions were synthesized and introduced through solid-phase synthesis
      into 15-mer oligodeoxynucleotide, GGTTGGTGTGGTTGG, which forms a chairlike
      structure consisting of two G-tetrads and is a potent thrombin inhibitor. The
      effects of the substitutions at N2 and C8 of the G-tetrad-forming G residues on
      the thrombin inhibitory activity are relatively small, suggesting that these
      substitutions cause relatively small perturbations on the chairlike structure
      formed by the oligodeoxynucleotide. Introduction of a benzyl group into N2 of G6
      and G11 and naphthylmethyl groups into N2 of G6 increased the thrombin inhibitory
      activity, whereas other substituents in these positions had almost no effect or
      decreased the activity. Particularly, the oligodeoxynucleotide carrying a 1
      naphthylmethyl group in the N2 position of G6 showed an increase in activity by
      about 60% both in vitro and in vivo. Substitutions on the N2 position of other G
      residues had little effect or decreased the activity. Introduction of a
      relatively small group, such as methyl and propynyl, into the C8 positions of G1,
      G5, G10, and G14 increased the activity, presumably due to the stabilization of a
      chairlike structure, whereas introduction of a large substituent group,
      phenylethynyl, decreased the activity, probably due to the steric hindrance.

PMID- 9632357
TI  - Benzylimidazolines as h5-HT1B/1D serotonin receptor ligands: a structure-affinity
      investigation.
AB  - Benzylimidazolines may represent a class of 5-HT1D ligands that has yet to be
      exploited. On the basis of a previous report that the 2-(substituted
      benzyl)imidazoline alpha-adrenergic agonist oxymetazoline (8) binds with high
      affinity at calf brain 5-HT1D receptors, we explored the structure-affinity
      relationships of a series of related derivatives. Each of the aromatic
      substituents was removed and then reinstated in a systematic manner to determine
      the influence of the individual substituents on binding. It was found that all of
      the aromatic substituents of 8 act in concert to impart high affinity. However,
      although the 3-hydroxy group could be removed without significantly reducing
      affinity for h5-HT1D (i.e., human 5-HT1Dalpha) receptors, this modification
      reduced h5-HT1B (i.e., human 5-HT1Dbeta) receptor affinity by nearly 50-fold. The
      2, 6-dimethyl groups also contribute to binding but seem to play a greater role
      for h5-HT1B binding than h5-HT1D binding. With the appropriate structural
      modifications, several compounds were identified that display 20- to >100-fold
      selectivity for h5-HT1D versus h5-HT1B receptors. Preliminary functional data
      suggest that these compounds behave as agonists. Given that 5-HT1D agonists are
      currently being explored for their antimigraine action and that activation of h5
      HT1B receptors might be associated with cardiovascular side effects, h5-HT1D
      selective agents may offer a new lead for the development of therapeutically
      efficacious agents.

PMID- 9632358
TI  - Discovery of a novel series of potent and selective substrate-based inhibitors of
      p60c-src protein tyrosine kinase: conformational and topographical constraints in
      peptide design.
AB  - On the basis of the efficient substrate for p60c-src protein tyrosine kinase
      (PTK) YIYGSFK-NH2 (1) (Km = 55 microM) obtained by combinatorial methods, we have
      designed and synthesized a series of conformationally and topographically
      constrained substrate-based peptide inhibitors of this enzyme, which showed IC50
      values in the low-micromolar range (1-3 microM). A "rotamer scan" was performed
      by introducing the four stereoisomers of beta-Me(2')Nal in the postulated
      interaction site of the peptide inhibitor 23(IC50 = 1.6 microM). This
      substitution led to selective and potent inhibitors of p60c-src PTK; however, no
      substantial difference in potency was observed among them. This and the results
      of the "stereochemical scan" performed at residues 2 and 7 of 3 (peptides 19-21),
      which form the disulfide bond, may suggest that the enzyme active site does not
      have rigid topographic requirements and thus is able to achieve important
      conformational changes to bind the ligand as long as the pharmacophore pattern in
      the inhibitor is conserved. Two new potent iodo-containing nonphosphorylatable
      tyrosine analogues were also incorporated into our lead inhibitory sequence 23,
      producing the most potent inhibitors for p60c-src PTK identified thus far in our
      studies. Compounds 29 and 30 exhibit IC50 values of 0.13 and 0.54 microM,
      respectively. Peptide 29 is 420-fold more potent than the parent peptide 1.
      Selectivity studies of peptides 23-30 toward p60c-src, Lyn, and Lck PTK showed in
      general high Lyn/Src and moderate Lck/Src selectivity ratios. We found that the
      chi1 space constraints of the specialized amino acids, introduced at position 3
      of the peptide lead 23, were not as important as the configuration of the Calpha
      of that residue to recognize the subtle chemical environment surrounding the
      active site of Src and Lck PTK, as reflected on the obtained Lck/Src selectivity
      ratios.

PMID- 9632359
TI  - Three-dimensional quantitative structure-activity relationship study of
      nonsteroidal estrogen receptor ligands using the comparative molecular field
      analysis/cross-validated r2-guided region selection approach.
AB  - A newly developed comparative molecular field analysis (CoMFA) technique, the
      cross-validated r2-guided region selection (CoMFA/q2-GRS) method, has been used
      to build a quantitative structure-activity relationship (3D-QSAR) for
      nonsteroidal estrogen receptor (ER) ligands. Ligands included in this study
      belong to a series of diethylstilbestrol (DES) and indenestrol analogues whose
      affinities for the mouse ER (mER) have been determined in our laboratory. The
      final model utilized 30 compounds and yielded a q2GRS (cross-validated r2, guided
      region selection) of 0.796, as compared to a q2 of 0.720 for conventional CoMFA,
      with a standard error of prediction of 0.594 at 3 principal components. This
      model was used to visualize steric and electrostatic features of the ligands that
      correspond with ER binding affinity. Results obtained from the CoMFA steric and
      electrostatic plots of this model have also been compared to information from the
      ER binding affinities of substituted estradiol analogues. This is in an effort to
      determine structural features of compounds in the CoMFA analysis that may
      correspond to those of the estradiol analogues and to further clarify the mode of
      binding of nonsteroidal ER ligands.

PMID- 9632360
TI  - 7-Oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridines as novel inhibitors of human
      eosinophil phosphodiesterase.
AB  - High-throughput file screening against inhibition of human lung PDE4 led to the
      discovery of 3-ethyl-1-(4-fluorophenyl)-6-phenyl-7-oxo-4, 5,6,7-tetrahydro-1H
      pyrazolo[3,4-c]pyridine (11) as a novel PDE4 inhibitor. Subsequent SAR
      development, using an eosinophil PDE assay, led to analogues up to 50-fold more
      potent than 11 with IC50 values of 0.03-1.6 microM. One such compound, CP-220,629
      (22) (IC50 = 0.44 microM), was efficacious in the guinea pig aerosolized antigen
      induced airway obstruction assay (ED50 2.0 mg/kg, po) and demonstrated a
      significant reduction in eosinophil (55%), neutrophil (65%), and IL-1beta (82%)
      responses to antigen challenge in atopic monkeys (10 mg/kg, po).

PMID- 9632361
TI  - Synthesis and glutathione S-transferase structure-affinity relationships of
      nonpeptide and peptidase-stable glutathione analogues.
AB  - A series of nonpeptidic glutathione analogues where the peptide bonds were
      replaced by simple carbon-carbon bonds or isosteric E double bonds were prepared.
      The optimal length for the two alkyl chains on either side of the mercaptomethyl
      group was evaluated using structure-affinity relationships. Affinities of the
      analogues 14a-f, 23, and 25 were evaluated for a recombinant GST enzyme using a
      new affinity chromatography method previously developed in our laboratory.
      Analysis of these analogues gives an additional understanding for GST affinity
      requirements: (a) the carbon skeleton must conserve that of glutathione since
      analogue 14a showed the best affinity (IC50 = 5.2 microM); (b) the GST G site is
      not able to accommodate a chain length elongation of one methylene group (no
      affinity for analogues 14c,f); (c) a one-methylene group chain length reduction
      is tolerated, much more for the "Glu side" (14d, IC50 = 10.1 microM) than for the
      "Gly side" (14b, IC50 = 1800 microM); (d) the mercaptomethyl group must remain at
      position 5 as shown from the null affinity of the 6-mercaptomethyl analogue 14e;
      (e) the additional peptide isosteric E double bond (25) or hydroxyl derivative
      (23) in 14e did not help to retrieve affinity. This work reveals useful
      information for the design of new selective nonpeptidic and peptidase-stable
      glutathione analogues.

PMID- 9632362
TI  - Synthesis and evaluation of diphenyl phosphonate esters as inhibitors of the
      trypsin-like granzymes A and K and mast cell tryptase.
AB  - Thirty-six new amino acid and peptidyl diphenyl phosphonate esters were
      synthesized and evaluated to identify potent and selective inhibitors for four
      trypsin-like proteases: lymphocyte granzymes A and K, human mast cell tryptase,
      and pancreatic trypsin. Among five Cbz derivatives of Lys and Arg homologues, Z
      (4-AmPhe)P(OPh)2 is the most potent inhibitor for granzyme A, and Z-LysP(OPh)2 is
      the best inhibitor for granzyme K, mast tryptase, and trypsin. The amidino P1
      residue D,L-(4-AmPhGly)P(OPh)2 was utilized in a series of compounds with several
      different N-protecting groups and systematic substitutions at P2 in Cbz-AA
      derivatives and at P3 in Cbz-AA-Ala derivatives. Generally, these phosphonates
      inhibit granzyme A and trypsin more potently than granzyme K and tryptase. The P2
      Thr and Ala dipeptide phosphonates, Cbz-AA-(4-AmPhGly)P(OPh)2, are the most
      potent inhibitors for granzyme A, and Cbz-Thr-(4-AmPhGly)P(OPh)2 (kobs/[I] = 2220
      M-1 s-1) was quite specific with much lower inhibition rates for granzyme K and
      trypsin (kobs/[I] = 3 and 97 M-1 s-1, respectively) and no inhibition with
      tryptase. The most effective inhibitor of granzyme A was Ph-SO2-Gly-Pro-(4
      AmPhGly)P(OPh)2 with a second-order rate constant of 3650 M-1 s-1. The most
      potent inhibitor for granzyme K was 3, 3-diphenylpropanoyl-Pro-(4-AmPhGly)P(OPh)2
      with a kobs/[I] = 1830 M-1 s-1; all other phosphonates inhibited granzyme K
      weakly (kobs/[I] < 60 M-1 s-1). Human mast cell tryptase was inhibited slowly by
      these phosphonates with Cbz-LysP(OPh)2 as the best inhibitor (kobs/[I] = 89 M-1 s
      1). The overall results suggest that scaffolds of Phe-Thr-(4-AmPhe) and Phe-Pro
      Lys will be useful to create selective phosphonate inhibitors for granzymes A and
      K, respectively, and that P4 substituents offer opportunities to further enhance
      selectivity and reactivity.

PMID- 9632363
TI  - Studies on selectin blockers. 6. Discovery of homologous fucose sugar unit
      necessary for E-selectin binding.
AB  - We describe a mimic of the sugar unit of the E-selectin ligand, sialyl Lewis X
      (sLeX). Carbohydrates are entering the realm of rational drug design, aided by
      the growing understanding of the structure-function relationships. We
      investigated a new methodology of preparing sLeX mimetics and developed a potent
      E-selectin blocker characterized by beta-turn dipeptides. Another characteristic
      point of this E-selectin blocker is that the six-membered fucose ring was
      replaced with a five-membered fucose ring. Interestingly, it was found that the
      five-membered fucose ring could also bind to a calcium ion on the E-selectin,
      which could be an important role of the six-membered fucose ring. Especially, the
      L-Ser-D-Glu and D-Ser-L-Glu derivatives 3a,b showed 65-90-fold more potent
      inhibitory activities than the sulfated LeX analogue 1. In addition, molecular
      dynamics (MD) studies indicated that the 2- and 3-OH groups of the six-membered
      fucose ring, which were necessary for the calcium binding, overlapped well with
      the 2- and 3-OH groups of the five-membered fucose ring. These new findings could
      be useful for the design of new types of selectin blockers.

PMID- 9632365
TI  - Comprehensive study on structure-activity relationships of rifamycins: discussion
      of molecular and crystal structure and spectroscopic and thermochemical
      properties of rifamycin O.
AB  - The mechanism of action of rifamycins against bacterial DNA-dependent RNA
      polymerase has been explained on the basis of the spatial arrangement of four
      oxygens which can form hydrogen bonds with the enzyme. Structural descriptors are
      derived from X-ray diffraction crystal structures of 25 active and nonactive
      rifamycins. Principal component analysis is used to find the combination of
      structural parameters which better discriminate between active and nonactive
      rifamycins. Two possible mechanisms of molecular rearrangement are described
      which can convert nonactive into active conformations. The energy involved for
      conformational rearrangements is studied by molecular modeling techniques. Methyl
      C34 is found to play a key role for determining the geometry of the
      pharmacophore. Rifamycin O, reported to be active, is obtained by oxidation of
      rifamycin B and is studied by X-ray single-crystal diffractometry, by solution IR
      and NMR spectroscopy, and by thermal analysis. Surprisingly the oxidation process
      is totally stereospecific, and an explanation is given based on solution
      spectroscopic evidence. The conformation found in the solid state is typical of
      nonactive compounds, and molecular mechanics calculations show that a molecular
      rearrangement to the active conformation would require about 15 kcal/mol. Thermal
      analysis confirms that rifamycin O has a sterically constrained conformation.
      Therefore, it is likely that the antibiotic activity of rifamycin O is due either
      to chemical modification prior to reaching the enzyme or to conformational
      activation.

PMID- 9632364
TI  - Synthesis and antitumor activity of ring A- and F-modified hexacyclic
      camptothecin analogues.
AB  - Nineteen ring A- and F-modified hexacyclic analogues of camptothecin were
      synthesized by Friedlander condensation of appropriately substituted bicyclic
      amino ketones with tricyclic ketone and were evaluated for cytotoxicity and
      topoisomerase I inhibitory activity. Seventeen of the compounds showed cytotoxic
      effects comparable or superior to those of 7-ethyl-10-hydroxycamptothecin (SN-38)
      against mouse leukemia P388 and human tumor cell lines HOC-21 and QG-56.
      Introduction of a compact and inductively electron-withdrawing substituent such
      as a hydroxy, methoxy, chloro, or fluoro group into position 5 of ring A of the
      hexacyclic compound remarkably increased the antitumor activity. The potency of
      topoisomerase I inhibition of these compounds showed good correlation with their
      cytotoxicity. Among them, the 4-methyl-5-fluoro hexacyclic compound was the most
      potent of all and was 10 times as active as SN-38 in in vitro antitumor activity.

PMID- 9632366
TI  - Structure-activity requirements for flavone cytotoxicity and binding to tubulin.
AB  - A series of 79 flavones related to centaureidin (3,6,4'-trimethoxy-5, 7,3'
      trihydroxyflavone, 1) was screened for cytotoxicity in the NCI in vitro 60-cell
      line human tumor screen. The resulting cytotoxicity profiles of these flavones
      were compared for degree of similarity to the profile of 1. Selected compounds
      were further evaluated with in vitro assays of tubulin polymerization and
      [3H]colchicine binding to tubulin. Maximum potencies for tubulin interaction and
      production of differential cytotoxicity profiles characteristic of 1 were
      observed only with compounds containing hydroxyl substituents at C-3' and C-5 and
      methoxyl groups at C-3 and C-4'.

PMID- 9632367
TI  - Auxiliary agents for the peroral administration of peptide and protein drugs:
      synthesis and evaluation of novel pepstatin analogues.
AB  - The peroral administration of (poly)peptide drugs requires the development of
      delivery systems, which provide a protective effect toward a gastrointestinal
      enzymatic attack. A promising strategy for such systems represents polymer-enzyme
      inhibitor conjugates in which the embedded therapeutic agent is protected.
      However, the practical use of polymer-inhibitor conjugates has so far been
      limited by high production costs of these auxiliary agents. To solve this problem
      for delivery systems shielding from pepsinic degradation, structurally simplified
      analogues of the pepsin inhibitor pepstatin A have been synthesized. The
      synthesis of tripeptide analogues, described by McConnell et al., led us to
      pursue further modifications varying the C-terminus. Our target to attach a
      spacer moiety-enabling the free access of pepsin to the inhibitor-should be
      combined with an attractive synthetic approach providing low production costs in
      large-scale preparation. Structure modifications comprised either the side chain
      of the third amino acid which served as starting compound designing the C
      terminus (L-leucine, L-isoleucine, L-norvaline) as the length of the spacer link,
      simulated by a linear alkyl group (n-butyl, n-hexyl, and n-octyl). The inhibitory
      activities which have been evaluated by an enzyme assay were significantly
      dependent on the nature of the side chain, whereas the length of the spacer had
      no influence on the inhibitory effect. Analogues bearing the isobutyl or n-propyl
      moiety as side chain displayed a strong inhibitory effect which was comparable to
      that pepstatin A. These congeners represent promising auxiliary agents for the
      peroral administration of (poly)peptide drugs.

PMID- 9632368
TI  - GPIIb/IIIa integrin antagonists with the new conformational restriction unit,
      trisubstituted beta-amino acid derivatives, and a substituted benzamidine
      structure.
AB  - Ethyl N-[3-(2-fluoro-4-(thiazolidin-3-yl(imino)methyl)benzoyl)amino-2, 2
      dimethylpentanoyl]piperidine-4-acetate 40 (NSL-96184) is a highly potent and
      orally active fibrinogen receptor antagonist, which is characterized by the
      presence of the trisubstituted beta-amino acid residue, 3-ethyl-2,2-dimethyl-beta
      alanine. This compound was developed on the basis of the SAR study of N-[3-(N-4
      amidinobenzoyl)amino-2, 2-dimethyl-3-phenylpropionyl]piperidine-4-acetic acid
      1(NSL-95301) with the derivatization focused on the central trisubstituted beta
      amino acid unit as well as the basic amidinobenzoyl unit, and the esterification
      of the carboxyl group for prodrug composition. Compound 1, which was reported in
      our previous study, was discovered by the application of combinatorial chemistry.
      The molecular modeling study suggests that the trisubstituted beta-amino acid
      unit is responsible for fixing the molecule to its active conformation. Compound
      40 showed an excellent profile in the in vitro and in vivo studies for its human
      platelet aggregation inhibitory activity and oral availability in guinea pigs.
      This oral availability largely depends on the modification of the amidino group
      with a cyclic secondary amine, i.e., thiazolidine in 40. In in vivo studies, the
      onset of the antiplatelet action of 40 is very fast after oral administration,
      whereas its duration of action is relatively short. These results suggest that 40
      has an excellent therapeutic potential, especially for antithrombotic treatment
      in the acute phase. 3-Substituted-2,2-dimethyl-beta-amino acid residues would
      serve as new and useful linear templates to restrict the conformational
      flexibility of peptidomimetics.

PMID- 9632369
TI  - Synthesis and quantitative structure-activity relationships of N-(1
      benzylpiperidin-4-yl)phenylacetamides and related analogues as potent and
      selective sigma1 receptor ligands.
AB  - A series of N-(1-benzylpiperidin-4-yl)phenylacetamide derivatives was synthesized
      and evaluated for affinity at sigma1 and sigma2 receptors. Most of these
      compounds showed a high affinity for sigma1 receptors and a low to moderate
      affinity for sigma2 receptors. The unsubstituted compound N-(1-benzylpiperidin-4
      yl)phenylacetamide, 1, displayed a high affinity and selectivity for sigma1
      receptors (Ki values of 3.90 nM for sigma1 receptors and 240 nM for sigma2
      receptors). The influence of substitutions on the phenylacetamide aromatic ring
      on binding at both the sigma1 and sigma2 receptor has been examined through
      Hansch-type quantitative structure-activity relationship (QSAR) studies. In
      general, all 3-substituted compounds, except for the OH group, had a higher
      affinity for both sigma1 and sigma2 receptors when compared with the
      corresponding 2- and 4-substituted analogues. The selectivity for sigma1
      receptors displayed a trend of 3 > 2 approximately 4 for Cl, Br, F, NO2, and OMe
      substituted analogues. Halogen substitution on the aromatic ring generally
      increased the affinity for sigma2 receptors while maintaining a similar affinity
      for sigma1 receptors. Substitution with electron-donating groups, such as OH,
      OMe, or NH2, resulted in weak or negligible affinity for sigma2 receptors and a
      moderate affinity for sigma1 receptors. The 2-fluoro-substituted analogue, 11,
      exhibited the highest selectivity for sigma1 receptors among all compounds
      tested, with a Ki value of 3.56 nM for sigma1 receptors and 667 nM for sigma2
      receptors. Compounds 1, 5, 9, 11, and 20 had no affinity for dopamine D2 (IC50 >
      10 000 nM) and D3 (IC50 > 10 000 nM) receptors. The nanomolar binding affinity
      and high selectivity for sigma1 receptors suggest that these compounds may be
      developed as potential radiotracers for positron emission tomography or single
      photon emission computerized tomography imaging studies.

PMID- 9632370
TI  - Syntheses and anticholinesterase activities of (3aS)-N1, N8-bisnorphenserine,
      (3aS)-N1,N8-bisnorphysostigmine, their antipodal isomers, and other potential
      metabolites of phenserine.
AB  - Hydrolysis of the carbamate side chains in phenserine [(-)1] and physostigmine [(
      )2] yields the metabolite (-)-eseroline (3), and the red dye rubreserine (4) on
      air oxidation of the former compound. Both compounds lacked anticholinesterase
      activity in concentrations up to 30 mM, which would be unachievable in vivo. A
      second group of potential metabolites of 1 and 2 are the N1,N8-bisnorcarbamates (
      )9 and (-)10, prepared from (3aS)-N8-benzylnoresermethole (-)12 by the
      carbinolamine route. These entirely novel compounds proved to be highly potent
      inhibitors of acetylcholinesterase [(-)9] and of acetyl- and
      butyrylcholinesterase (AChE and BChE) [(-)10], respectively. To elucidate further
      the structure/anticholinesterase activity relationship of the described
      compounds, the antipodal isomers (3aR)-N1,N8-bisnorcarbamates (+)9 and (+)10 were
      likewise synthesized from (3aR)-N8-benzylnoresermethole (+)12 and assessed. The
      compounds possessed moderate but less potent anticholinesterase activity, with
      the same selectivity as their 3aS enantiomers. Finally, the anticholinesterase
      activities of intermediates N1, N8-bisnorbenzylcarbamates (-)18, (-) 19, (+)18,
      and (+)19, also novel compounds, were additionally measured. The 3aS enantiomers
      proved to be potent and selective inhibitors of BChE, particularly (-)19, whereas
      the antipodal isomers lacked activity.

PMID- 9632371
TI  - 2beta-Substituted analogues of 4'-iodococaine: synthesis and dopamine transporter
      binding potencies.
AB  - A series of 2beta-substituted analogues of 4'-iodococaine (3) was synthesized and
      evaluated in an in vitro dopamine transporter (DAT) binding assay. Selective
      hydrolysis at the 2beta-position of 3 gave the carboxylic acid 15 that served as
      the intermediate for the synthesis of compounds 4, 5, and 6-11. The 2beta-alkyl
      derivatives were obtained from ecgonine methyl ester (17) through a series of
      reactions leading to the aldehyde 20. Wittig reaction of 20 with
      methyltriphenylphosphorane followed by hydrogenation and benzoylation gave the
      products 12 and 13. The binding affinity of 4'-iodococaine (3) was 10-fold less
      than that of cocaine. The hydroxymethane, acetate, amide, benzyl ester,
      oxidazole, and ethane derivatives of 3 exhibited decreased binding while the
      vinyl, phenyl, and ethyl esters showed a moderate increase in binding affinity.
      Only the isopropyl derivative 8 exhibited a 2-fold increase in binding affinity
      compared with 4'-iodococaine (3). Hydroxylation of 8 at the 2'-position gave 14
      which enhanced not only the binding potency at the DAT by another 2-fold but also
      the selectivity at the DAT over the norepinephrine and serotonin transporters.
      Compound 14 failed to stimulate locomotor activity in C57BL/6J mice over a wide
      dose range and blocked cocaine-induced locomotor stimulant action.

PMID- 9632372
TI  - Inhibitors of acyl-CoA:cholesterol O-acyltransferase. 2. Identification and
      structure-activity relationships of a novel series of N-alkyl-N-(heteroaryl
      substituted benzyl)-N'-arylureas.
AB  - A series of N-alkyl-N-(heteroaryl-substituted benzyl)-N'-arylurea and related
      derivatives represented by 2 and 3 have been prepared and evaluated for their
      ability to inhibit acyl-CoA:cholesterol O-acyltransferase in vitro and to lower
      plasma cholesterol levels in cholesterol-fed rats in vivo. Among these novel
      compounds, the type 3 series was superior. A pyrazol-3-yl group on the N-benzyl
      group of this trisubstituted urea (i.e. 3, Ar1 = pyrazol-3-yl) was identified as
      a heteroaromatic ring providing a good profile of biological activity. As a
      result of optimization of the combination with the N-alkyl group (R) and N-aryl
      group (Ar3), compound 3aq (FR186054) was identified as a new, orally efficacious
      ACAT inhibitor, which exhibited potent in vitro ACAT inhibitory activity (rabbit
      intestinal microsomes IC50 = 99 nM) and excellent hypocholesterolemic effects in
      cholesterol-fed rats, irrespective of administration mode (ED50 = 0.046 mg/kg
      dosed via the diet, ED50 = 0. 44 mg/kg administered by gavage in PEG400 vehicle).
      Moreover, a toxicological study revealed compound 3aq to be nontoxic to the
      adrenal glands of dogs when tested at a single dose of 10 mg/kg po.

PMID- 9632373
TI  - Nonsymmetric P2/P2' cyclic urea HIV protease inhibitors. Structure-activity
      relationship, bioavailability, and resistance profile of monoindazole-substituted
      P2 analogues.
AB  - Using the structural information gathered from the X-ray structures of various
      cyclic urea/HIVPR complexes, we designed and synthesized many nonsymmetrical
      P2/P2'-substituted cyclic urea analogues. Our efforts concentrated on using an
      indazole as one of the P2 substituents since this group imparted enzyme (Ki)
      potency as well as translation into excellent antiviral (IC90) potency. The
      second P2 substituent was used to adjust the physical and chemical properties in
      order to maximize oral bioavailability. Using this approach several very potent
      (IC90 11 nM) and orally bioavailable (F% 93-100%) compounds were discovered (21,
      22). However, the resistance profiles of these compounds were inadequate,
      especially against the double (I84V/V82F) and ritonavir-selected mutant viruses.
      Further modification of the second P2 substituent in order to increase H-bonding
      interactions with the backbone atoms of residues Asp 29, Asp 30, and Gly 48 led
      to analogues with much better resistance profiles. However, these larger
      analogues were incompatible with the apparent molecular weight requirements for
      good oral bioavailability of the cyclic urea class of HIVPR inhibitors (MW <
      610).

PMID- 9632374
TI  - Optimizing the binding of fullerene inhibitors of the HIV-1 protease through
      predicted increases in hydrophobic desolvation.
AB  - We have developed and applied a computational strategy to increase the affinity
      of fullerene-based inhibitors of the HIV protease. The result is a approximately
      50-fold increase in affinity from previously tested fullerene compounds. The
      strategy is based on the design of derivatives which may potentially increase
      hydrophobic desolvation upon complex formation, followed by the docking of the
      hypothetical derivatives into the HIV protease active site and assessment of the
      model complexes so formed. The model complexes are generated by the program DOCK
      and then analyzed for desolvated hydrophobic surface. The amount of hydrophobic
      surface desolvated was compared with a previously tested compound, and if this
      amount was significantly greater, it was selected as a target. Using this
      approach, two targets were identified and synthesized, using two different
      synthetic approaches: a diphenyl C60 alcohol (5) based on a cyclopropyl
      derivative of Bingel (Chem.Ber. 1993, 126, 1957-1959) and a diisopropyl
      cyclohexyl C60 alcohol (4a) as synthesized by Ganapathi et al. (J. Org.Chem.
      1995, 60, 2954-2955). Both showed tighter binding than the originally tested
      compound (diphenethylaminosuccinate methano-C60, Ki = 5 microM) with Ki values of
      103 and 150 nM, respectively. In addition to demonstrating the utility of this
      approach, it shows that simple modification of fullerenes can result in high
      affinity ligands of the HIV protease, for which they are highly complementary in
      structure and chemical nature.

PMID- 9632375
TI  - Synthesis and dopamine transporter affinity of the four stereoisomers of (+/-)-2
      (methoxycarbonyl)-7-methyl-3-phenyl-7-azabicyclo[2.2.1]heptane.
AB  - All four stereoisomers of (+/-)-2-(methoxycarbonyl)-7-methyl-3-phenyl-7
      azabicyclo[2.2. 1]heptane were synthesized and evaluated as cocaine binding site
      ligands at the dopamine transporter. The in vitro binding affinities (Ki) of the
      7-azabicyclo[2.2.1]heptane derivatives were measured in rat caudate-putamen
      tissue and found to be 100-3000-fold less potent (Ki = 5-96 microM) than cocaine
      and 2beta-(methoxycarbonyl)-3beta-phenyltropane (2, WIN 35,065-2). Surprisingly,
      the 3alpha-phenyl isomers (6c, 6d) were more potent than the 3beta-phenyl isomers
      (6a, 6b). Molecular modeling studies revealed that the rigid 7
      azabicyclo[2.2.1]heptane derivatives possess molecular topologies which are
      significantly different than the molecular topologies of the 2beta
      (methoxycarbonyl)-3-phenyltropanes.

PMID- 9632376
TI  - Antimycobacterial activity of substituted isosteres of pyridine- and
      pyrazinecarboxylic acids.
AB  - Pyrazines and pyridines substituted with alkylated tetrazoles, esterified
      vinylogous carboxylic acids, and ketosulfides were synthesized as precursors of
      antimycobacterial agents which, after penetration of the mycobacterial cell wall,
      could be biotransformed by esterases or peroxidase-catalases. The expected
      products are tetrazoles, a vinylogous carboxylic acid, and CH-acidic
      ketosulfoxides, isosteres of pyrazinoic and nicotinic acids, which should inhibit
      mycobacterial growth when released inside the bacterial cell. The growth
      inhibitory activity of the synthesized compounds against the H37Rv strain of
      Mycobacterium tuberculosis was determined to assess the viability of this
      concept. It was shown that all of the compounds designed as lipophilic precursors
      were more active than the unmodified polar isosteres of pyrazinoic and nicotinic
      acids.

PMID- 9632377
TI  - DNA strand exchange proteins: a biochemical and physical comparison.
AB  - Homologous genetic recombination is an essential biological process that involves
      the pairing and exchange of DNA between two homologous chromosomes or DNA
      molecules. It is of fundamental importance to the preservation of genomic
      integrity, the production of genetic diversity, and the proper segregation of
      chromosomes. In Escherichia coli, the RecA protein is essential to recombination,
      and biochemical analysis demonstrates that it is responsible for the crucial
      steps of homologous pairing and DNA strand exchange. The presence of RecA-like
      proteins, or their functional equivalents, in bacteriophage, other eubacteria,
      archaea, and eukaryotes, confirms that the mechanism of homologous pairing and
      DNA strand exchange is conserved throughout all forms of life. This review
      focuses on the biochemical and physical characteristics of DNA strand exchange
      proteins from three diverse organisms: RecA protein from E. coli, UvsX protein
      from Bacteriophage T4, and RAD51 protein from Saccharomyces cerevisiae.

PMID- 9632378
TI  - The Alzheimer's plaques, tangles and memory deficits may have a common origin.
      Part III: animal model.
AB  - We have hypothesized that an intracellular calcium deficit may occur in the early
      phase of Alzheimer's disease (AD). This hypothesis has two important corollaries.
      First, it predicts that elevation of calcium levels by many calcium agonists, in
      principle, would have protective effects in the individuals at-risk to AD.
      Second, it implies that an artificial decrease of the calcium levels by the use
      of calcium antagonists might mimic the AD pathologies in the experimental
      animals. Obviously, the latter prediction not only would allow a direct testing
      of the hypothesis, but also might offer a "new" route for developing an animal
      model for sporadic AD. In fact, a number of the existing models that target
      various neurotransmitter receptors and calcium channels has manifested memory
      deficits. This suggests that a fully successful animal model for AD might be
      developed by improving the current paradigms. Furthermore, we discuss a potential
      relationship between AD and schizophrenia in terms of intracellular calcium
      imbalance.

PMID- 9632379
TI  - Progress in the development of an HIV-1 vaccine.
AB  - Containment of the acquired immunodeficiency syndrome (AIDS) epidemic will
      require an effective human immunodeficiency virus type 1 (HIV-1) vaccine.
      Accumulating evidence suggests that such a vaccine must efficiently elicit an HIV
      1-specific cytotoxic T lymphocyte (CTL) response. Nonhuman primate models will
      continue to provide an important tool for assessing the extent of protective
      immunity induced by various immunization strategies. Although replication
      competent AIDS viruses attenuated for pathogenicity by selective gene deletions
      have provided protective immunity in nonhuman primate models, the long-term
      safety of such vaccines in human populations is suspect. Inactivated virus and
      subunit vaccines have elicited neither CTLs nor antibodies capable of
      neutralizing a wide array of patient HIV-1 isolates. Considerable effort is now
      being focused on evaluating live vector-based vaccine and plasmid DNA vaccine
      approaches for preventing HIV-1 infection both in animal model and human studies.
      Our growing understanding of the biology of HIV-1 and immune responses to this
      virus will continue to suggest improved vaccination approaches for exploration.

PMID- 9632380
TI  - HIV-1 regulatory/accessory genes: keys to unraveling viral and host cell biology.
AB  - Human immunodeficiency virus type-1 (HIV-1) manipulates fundamental host cell
      processes in sophisticated ways to achieve optimum replicative efficiency. Recent
      studies have provided new details on the molecular interactions of HIV-1 with its
      host cell. For example, HIV-1 encodes a protein that regulates transcriptional
      elongation by interacting with a cellular cyclin-dependent kinase, another that
      activates the specific nuclear export of viral RNA, and several others that
      affect the intracellular trafficking of viral and host cell proteins. Detailed
      analysis of the interplay between these viral proteins and normal cellular
      activities has provided new insights into central questions of virology and host
      cell biology.

PMID- 9632381
TI  - The HIV-1 envelope glycoproteins: fusogens, antigens, and immunogens.
AB  - The human immunodeficiency virus-type 1 (HIV-1) envelope glycoproteins interact
      with receptors on the target cell and mediate virus entry by fusing the viral and
      cell membranes. The structure of the envelope glycoproteins has evolved to
      fulfill these functions while evading the neutralizing antibody response. An
      understanding of the viral strategies for immune evasion should guide attempts to
      improve the immunogenicity of the HIV-1 envelope glycoproteins and, ultimately,
      aid in HIV-1 vaccine development.

PMID- 9632382
TI  - The NIMH Multisite HIV Prevention Trial: reducing HIV sexual risk behavior. The
      National Institute of Mental Health (NIMH) Multisite HIV Prevention Trial Group.
AB  - The efficacy of a behavioral intervention to reduce human immunodeficiency virus
      (HIV) risk behaviors was tested in a randomized, controlled trial with three high
      risk populations at 37 clinics from seven sites across the United States.
      Compared with the 1855 individuals in the control condition, the 1851
      participants assigned to a small-group, seven-session HIV risk reduction program
      reported fewer unprotected sexual acts, had higher levels of condom use, and were
      more likely to use condoms consistently over a 12-month follow-up period. On the
      basis of clinical record review, no difference in overall sexually transmitted
      disease (STD) reinfection rate was found between intervention and control
      condition participants. However, among men recruited from STD clinics, those
      assigned to the intervention condition had a gonorrhea incidence rate one-half
      that of those in the control condition. Intervention condition participants also
      reported fewer STD symptoms over the 12-month follow-up period. Study outcomes
      suggest that behavioral interventions can reduce HIV-related sexual risk behavior
      among low-income women and men served in public health settings. Studies that
      test strategies for reducing sexual risk behavior over longer periods of time are
      needed, especially with populations that remain most vulnerable to HIV infection.

PMID- 9632383
TI  - Black carbon in deep-Sea sediments 
AB  - Black carbon (BC) enters the ocean through aerosol and river deposition. BC makes
      up 12 to 31 percent of the sedimentary organic carbon (SOC) at two deep ocean
      sites, and it is 2400 to 13,900 carbon-14 years older than non-BC SOC deposited
      concurrently. BC is likely older because it is stored in an intermediate
      reservoir before sedimentary deposition. Possible intermediate pools are oceanic
      dissolved organic carbon (DOC) and terrestrial soils. If DOC is the intermediate
      reservoir, then BC is 4 to 22 percent of the DOC pool. If soils are the
      intermediate reservoir, then the importance of riverine carbon in the ocean
      carbon cycle has been underestimated.

PMID- 9632384
TI  - Elasticity of single-crystal MgO to 8 gigapascals and 1600 kelvin 
AB  - The cross pressure (P) and temperature (T) dependence of the elastic moduli (Cij)
      of single-crystal samples of periclase (MgO) from acoustic wave travel times was
      measured with ultrasonic interferometry: partial differential2C11/ partial
      differentialP partial differentialT = (-1.3 +/- 0.4) x 10(-3) per kelvin; partial
      differential2C110/ partial differentialP partial differentialT = (1. 7 +/- 0.7) x
      10(-3) per kelvin; and partial differential2C44/ partial differentialP partial
      differentialT = (-0.2 +/- 0.3) x 10(-3) per kelvin. The elastic anisotropy of MgO
      decreases with increasing pressure at ambient temperature, but then increases as
      temperature is increased at high pressure. An assumption of zero cross pressure
      and temperature derivatives for the elastic moduli underestimates the elastic
      anisotropy and overestimates the acoustic velocities of MgO at the extrapolated
      high-pressure and high-temperature conditions of Earth's mantle.

PMID- 9632385
TI  - The influence of vegetation-atmosphere-ocean interaction on climate during the
      mid-holocene 
AB  - Simulations with a synchronously coupled atmosphere-ocean-vegetation model show
      that changes in vegetation cover during the mid-Holocene, some 6000 years ago,
      modify and amplify the climate system response to an enhanced seasonal cycle of
      solar insolation in the Northern Hemisphere both directly (primarily through the
      changes in surface albedo) and indirectly (through changes in oceanic
      temperature, sea-ice cover, and oceanic circulation). The model results indicate
      strong synergistic effects of changes in vegetation cover, ocean temperature, and
      sea ice at boreal latitudes, but in the subtropics, the atmosphere-vegetation
      feedback is most important. Moreover, a reduction of the thermohaline circulation
      in the Atlantic Ocean leads to a warming of the Southern Hemisphere.

PMID- 9632386
TI  - Planar patterned magnetic media obtained by ion irradiation 
AB  - By ion irradiation through a lithographically made resist mask, the magnetic
      properties of cobalt-platinum simple sandwiches and multilayers were patterned
      without affecting their roughness and optical properties. This was demonstrated
      on arrays of 1-micrometer lines by near- and far-field magnetooptical microscopy.
      The coercive force and magnetic anisotropy of the irradiated regions can be
      accurately controlled by the irradiation fluence. If combined with high
      resolution lithography, this technique holds promise for ultrahigh-density
      magnetic recording applications.

PMID- 9632387
TI  - Post-cambrian trilobite diversity and evolutionary faunas 
AB  - A cluster analysis of the stratigraphic distribution of all Ordovician trilobite
      families, based on a comprehensive taxonomic database, identified two major
      faunas with disjunct temporal diversity trends. The Ibex Fauna behaved as a
      cohort, declining through the Ordovician and disappearing at the end-Ordovician
      mass extinction. In contrast, the Whiterock Fauna radiated rapidly during the
      Middle Ordovician and gave rise to all post-Ordovician trilobite diversity. Its
      pattern of diversification matches that of the Paleozoic Evolutionary Fauna;
      hence, trilobites were active participants in the great Ordovician radiations.
      Extinction patterns at the end of the Ordovician are related to clade size:
      Surviving trilobite families show higher genus diversity than extinguished
      families.

PMID- 9632388
TI  - Visualization of the local insulator-metal transition in Pr0.7Ca0. 3MnO3 
AB  - The light-induced insulator-metal transition in the "colossal magnetoresistance"
      compound Pr0.7Ca0.3MnO3 is shown to generate a well-localized conducting path
      while the bulk of the sample remains insulating. The path can be visualized
      through a change of reflectivity that accompanies the phase transition. Its
      visibility provides a tool for gaining insight into electronic transport in
      materials with strong magnetic correlations. For example, a conducting path can
      be generated or removed at an arbitrary position just because of the presence of
      another path. Such manipulation may be useful in the construction of optical
      switches.

PMID- 9632389
TI  - Call duration as an indicator of genetic quality in male gray tree frogs.
AB  - The "good genes" hypothesis predicts that mating preferences enable females to
      select mates of superior genetic quality. The genetic consequences of the
      preference shown by female gray tree frogs for long-duration calls were evaluated
      by comparing the performance of maternal half-siblings sired by males with
      different call durations. Offspring of male gray tree frogs that produced long
      calls showed better performance during larval and juvenile stages than did
      offspring of males that produced short calls. These data suggest that call
      duration can function as a reliable indicator of heritable genetic quality.

PMID- 9632390
TI  - Neural correlates of perceptual rivalry in the human brain.
AB  - When dissimilar images are presented to the two eyes, perception alternates
      spontaneously between each monocular view, a phenomenon called binocular rivalry.
      Functional brain imaging in humans was used to study the neural basis of these
      subjective perceptual changes. Cortical regions whose activity reflected
      perceptual transitions included extrastriate areas of the ventral visual pathway,
      and parietal and frontal regions that have been implicated in spatial attention;
      whereas the extrastriate areas were also engaged by nonrivalrous perceptual
      changes, activity in the frontoparietal cortex was specifically associated with
      perceptual alternation only during rivalry. These results suggest that
      frontoparietal areas play a central role in conscious perception, biasing the
      content of visual awareness toward abstract internal representations of visual
      scenes, rather than simply toward space.

PMID- 9632391
TI  - Proton transfer pathways in bacteriorhodopsin at 2.3 angstrom resolution.
AB  - Photoisomerization of the retinal of bacteriorhodopsin initiates a cyclic
      reaction in which a proton is translocated across the membrane. Studies of this
      protein promise a better understanding of how ion pumps function. Together with a
      large amount of spectroscopic and mutational data, the atomic structure of
      bacteriorhodopsin, determined in the last decade at increasing resolutions, has
      suggested plausible but often contradictory mechanisms. X-ray diffraction of
      bacteriorhodopsin crystals grown in cubic lipid phase revealed unexpected two
      fold symmetries that indicate merohedral twinning along the crystallographic c
      axis. The structure, refined to 2.3 angstroms taking this twinning into account,
      is different from earlier models, including that most recently reported. One of
      the carboxyl oxygen atoms of the proton acceptor Asp85 is connected to the proton
      donor, the retinal Schiff base, through a hydrogen-bonded water and forms a
      second hydrogen bond with another water. The other carboxyl oxygen atom of Asp85
      accepts a hydrogen bond from Thr89. This structure forms the active site. The
      nearby Arg82 is the center of a network of numerous hydrogen-bonded residues and
      an ordered water molecule. This network defines the pathway of the proton from
      the buried Schiff base to the extracellular surface.

PMID- 9632392
TI  - Bloodstream- versus tick-associated variants of a relapsing fever bacterium.
AB  - The relapsing fever spirochete, Borrelia hermsii, alternates infections between a
      mammal and a tick vector. Whether the spirochete changes phenotypically in the
      different hosts was examined by allowing the tick vector Ornithodoros hermsi to
      feed on mice infected with serotype 7 or serotype 8 of B. hermsii. Upon infection
      of ticks, the spirochetal serotype-specific variable major proteins (Vmps) 7 and
      8 became undetectable and were replaced by Vmp33. This switch from a bloodstream-
      to tick-associated phenotype could be induced in culture by a decrease in
      temperature. After tick-bite transmission back to mice, the process was reversed
      and the spirochetes resumed expression of the same Vmp present in the previous
      infectious blood meal.

PMID- 9632393
TI  - Gating of CaMKII by cAMP-regulated protein phosphatase activity during LTP.
AB  - Long-term potentiation (LTP) at the Schaffer collateral-CA1 synapse involves
      interacting signaling components, including calcium (Ca2+)/calmodulin-dependent
      protein kinase II (CaMKII) and cyclic adenosine monophosphate (cAMP) pathways.
      Postsynaptic injection of thiophosphorylated inhibitor-1 protein, a specific
      inhibitor of protein phosphatase-1 (PP1), substituted for cAMP pathway activation
      in LTP. Stimulation that induced LTP triggered cAMP-dependent phosphorylation of
      endogenous inhibitor-1 and a decrease in PP1 activity. This stimulation also
      increased phosphorylation of CaMKII at Thr286 and Ca2+-independent CaMKII
      activity in a cAMP-dependent manner. The blockade of LTP by a CaMKII inhibitor
      was not overcome by thiophosphorylated inhibitor-1. Thus, the cAMP pathway uses
      PP1 to gate CaMKII signaling in LTP.

PMID- 9632394
TI  - A calcium sensor homolog required for plant salt tolerance.
AB  - Excessive sodium (Na+) in salinized soils inhibits plant growth and development.
      A mutation in the SOS3 gene renders Arabidopsis thaliana plants hypersensitive to
      Na+-induced growth inhibition. SOS3 encodes a protein that shares significant
      sequence similarity with the calcineurin B subunit from yeast and neuronal
      calcium sensors from animals. The results suggest that intracellular calcium
      signaling through a calcineurin-like pathway mediates the beneficial effect of
      calcium on plant salt tolerance.

PMID- 9632395
TI  - Stabilization of interleukin-2 mRNA by the c-Jun NH2-terminal kinase pathway.
AB  - Signaling pathways that stabilize interleukin-2 (IL-2) messenger RNA (mRNA) in
      activated T cells were examined. IL-2 mRNA contains at least two cis elements
      that mediated its stabilization in response to different signals, including
      activation of c-Jun amino-terminal kinase (JNK). This response was mediated
      through a cis element encompassing the 5' untranslated region (UTR) and the
      beginning of the coding region. IL-2 transcripts lacking this 5' element no
      longer responded to JNK activation but were still responsive to other signals
      generated during T cell activation, which were probably sensed through the 3'
      UTR. Thus, multiple elements within IL-2 mRNA modulate its stability in a
      combinatorial manner, and the JNK pathway controls turnover as well as synthesis
      of IL-2 mRNA.

PMID- 9632396
TI  - A conserved HIV gp120 glycoprotein structure involved in chemokine receptor
      binding.
AB  - The entry of primate immunodeficiency viruses into target cells depends on a
      sequential interaction of the gp120 envelope glycoprotein with the cellular
      receptors, CD4 and members of the chemokine receptor family. The gp120 third
      variable (V3) loop has been implicated in chemokine receptor binding, but the use
      of the CCR5 chemokine receptor by diverse primate immunodeficiency viruses
      suggests the involvement of an additional, conserved gp120 element. Through the
      use of gp120 mutants, a highly conserved gp120 structure was shown to be critical
      for CCR5 binding. This structure is located adjacent to the V3 loop and contains
      neutralization epitopes induced by CD4 binding. This conserved element may be a
      useful target for pharmacologic or prophylactic intervention in human
      immunodeficiency virus (HIV) infections.

PMID- 9632397
TI  - Suboptimal care of patients before admission to intensive care. is caused by a
      failure to appreciate or apply the ABCs of life support.

PMID- 9632398
TI  - Hormone replacement therapy again. Risk-benefit relation differs between
      populations and individuals.

PMID- 9632399
TI  - 1998 European guidelines on resuscitation. Simplifications should make them
      easier to teach and implement.

PMID- 9632400
TI  - Why all the fuss about genetically modified food?. Much depends on who benefits.

PMID- 9632401
TI  - Planning the United Kingdom's medical workforce. On present assumptions UK
      medical school intake needs to increase.

PMID- 9632402
TI  - Making self regulation credible. Through benchmarking, peer review, appraisal-and
      management.

PMID- 9632403
TI  - Confidential inquiry into quality of care before admission to intensive care.
AB  - OBJECTIVE: To examine the prevalence, nature, causes, and consequences of
      suboptimal care before admission to intensive care units, and to suggest possible
      solutions. DESIGN: Prospective confidential inquiry on the basis of structured
      interviews and questionnaires. SETTING: A large district general hospital and a
      teaching hospital. SUBJECTS: A cohort of 100 consecutive adult emergency
      admissions, 50 in each centre. MAIN OUTCOME MEASURES: Opinions of two external
      assessors on quality of care especially recognition, investigation, monitoring,
      and management of abnormalities of airway, breathing, and circulation, and oxygen
      therapy and monitoring. RESULTS: Assessors agreed that 20 patients were well
      managed (group 1) and 54 patients received suboptimal care (group 2). Assessors
      disagreed on quality of management of 26 patients (group 3). The casemix and
      severity of illness, defined by the acute physiology and chronic health
      evaluation (APACHE II) score, were similar between centres and the three groups.
      In groups 1, 2, and 3 intensive care mortalities were 5 (25%), 26 (48%), and 6
      (23%) respectively (P=0.04) (group 1 versus group 2, P=0.07). Hospital
      mortalities were 7 (35%), 30 (56%), and 8 (31%) (P=0.07) and standardised
      hospital mortality ratios (95% confidence intervals) were 1.23 (0.49 to 2.54),
      1.4 (0.94 to 2.0), and 1.26 (0.54 to 2.48) respectively. Admission to intensive
      care was considered late in 37 (69%) patients in group 2. Overall, a minimum of
      4.5% and a maximum of 41% of admissions were considered potentially avoidable.
      Suboptimal care contributed to morbidity or mortality in most instances. The main
      causes of suboptimal care were failure of organisation, lack of knowledge,
      failure to appreciate clinical urgency, lack of supervision, and failure to seek
      advice. CONCLUSIONS: The management of airway, breathing, and circulation, and
      oxygen therapy and monitoring in severely ill patients before admission to
      intensive care units may frequently be suboptimal. Major consequences may include
      increased morbidity and mortality and requirement for intensive care. Possible
      solutions include improved teaching, establishment of medical emergency teams,
      and widespread debate on the structure and process of acute care.

PMID- 9632404
TI  - Hormone replacement therapy and risk of hip fracture: population based case
      control study. The Swedish Hip Fracture Study Group.
AB  - OBJECTIVE: To determine the relative risk of hip fracture associated with
      postmenopausal hormone replacement therapy including the effect of duration and
      recency of treatment, the addition of progestins, route of administration, and
      dose. DESIGN: Population based case-control study. SETTING: Six counties in
      Sweden. SUBJECTS: 1327 women aged 50-81 years with hip fracture and 3262 randomly
      selected controls. MAIN OUTCOME MEASURE: Use of hormone replacement therapy.
      RESULTS: Compared with women who had never used hormone replacement therapy,
      current users had an odds ratio of 0.35 (95 % confidence interval 0.24 to 0.53)
      for hip fracture and former users had an odds ratio of 0.76 (0.57 to 1.01). For
      every year of therapy, the overall risk decreased by 6% (3% to 9%): 4% (1% to 8%)
      for regimens without progestin and 11% (6% to 16%) for those with progestin. Last
      use between one and five years previously, with a duration of use more than five
      years, was associated with an odds ratio of 0.27 (0.08 to 0.94). After five years
      without hormone replacement therapy the protective effect was substantially
      diminished (-7% to 48%). With current use, an initiation of therapy nine or more
      years after the menopause gave equally strong reduction in risk for hip fracture
      as an earlier start. Oestrogen treatment with skin patches gave similar risk
      estimates as oral regimens. CONCLUSIONS: Recent use of hormone replacement
      therapy is required for optimum fracture protection, but therapy can be started
      several years after the menopause. The protective effect increases with duration
      of use, and an oestrogen-sparing effect is achieved when progestins are included
      in the regimen.

PMID- 9632406
TI  - The 1998 European Resuscitation Council guidelines for adult single rescuer basic
      life support. Basic Life Support Working Group of the European Resuscitation
      Council.

PMID- 9632407
TI  - Simple tests for septic bursitis: comparative study.

PMID- 9632408
TI  - What's a parameter? 

PMID- 9632405
TI  - The 1998 European Resuscitation Council guidelines for adult advanced life
      support. Advanced Life Support Working Group of the European Resuscitation
      Council.

PMID- 9632409
TI  - Qualitative study of patients' perceptions of doctors' advice to quit smoking:
      implications for opportunistic health promotion.
AB  - OBJECTIVES: To determine the effectiveness and acceptability of general
      practitioners'opportunistic antismoking interventions by examining detailed
      accounts of smokers' experiences of these. DESIGN: Qualitative semistructured
      interview study. SETTING: South Wales. SUBJECTS: 42 participants in the Welsh
      smoking intervention study were asked about initial smoking, attempts to quit,
      thoughts about future smoking, past experiences with the health services, and the
      most appropriate way for health services to help them and other smokers. RESULTS:
      Main emerging themes were that subjects already made their own evaluations about
      smoking, did not believe doctors' words could influence their smoking, believed
      that quitting was down to the individual, and felt that doctors who took the
      opportunity to talk about smoking should focus on the individual patient. Smokers
      anticipated that they would be given antismoking advice by doctors when attending
      for health care; they reacted by shrugging this off, feeling guilty, or becoming
      annoyed. These reactions affected the help seeking behaviour of some respondents.
      Smokers were categorised as "contrary," "matter of fact," and "self blaming,"
      depending on their reported reaction to antismoking advice. CONCLUSIONS: Doctor
      patient relationships can be damaged if doctors routinely advise all smokers to
      quit. Where doctors intervene, a patient centred approach-one that considers how
      individual patients view themselves as smokers and how they are likely to react
      to different styles of intervention-is the most acceptable.

PMID- 9632410
TI  - Primary care: core values. Patient centred primary care.

PMID- 9632411
TI  - Postnatal depression.

PMID- 9632413
TI  - It pays to be specific 

PMID- 9632412
TI  - Acute obstructive hydrocephalus complicating bacterial meningitis in childhood.

PMID- 9632414
TI  - Ethical debate. Truth, the first casualty. Deadly charades.

PMID- 9632415
TI  - Action on clinical audit: progress report.

PMID- 9632416
TI  - Managing demand in general practice.

PMID- 9632417
TI  - Understanding controlled trials. Randomising groups of patients.

PMID- 9632418
TI  - Reducing the vertical transmission of HIV. Women should be tested at time of
      abortion.

PMID- 9632419
TI  - Late diagnosis of HIV infection in children causes distress.

PMID- 9632420
TI  - Risk of breast cancer is also increased among retired US female airline cabin
      attendants.

PMID- 9632421
TI  - Intractable problems need long term solutions, not quick fixes.

PMID- 9632422
TI  - Copper is unlikely to cause contact allergy.

PMID- 9632423
TI  - Topical chloramphenicol is an outmoded treatment.

PMID- 9632424
TI  - Screening for prostate cancer. Key studies have only just started.

PMID- 9632425
TI  - The use or uselessness of annual public health reports. Response from author of
      report.

PMID- 9632426
TI  - Treating Helicobacter pylori infection after surgery is unnecessary.

PMID- 9632427
TI  - WMA urges national medical associations to ensure that economic sanctions respect
      agreed exemptions.

PMID- 9632428
TI  - Clinical trials should be designed to include elderly people.

PMID- 9632429
TI  - Why clinical audit doesn't work. Clinical audit in nursing homes has proved
      ineffective.

PMID- 9632430
TI  - Having electronic preprints is logical.

PMID- 9632431
TI  - Education still needs to be improved for trainee doctors.

PMID- 9632433
TI  - Junior doctors conference 

PMID- 9632432
TI  - Norman john badham 

PMID- 9632434
TI  - My role model 

PMID- 9632435
TI  - The credibility gap 

PMID- 9632436
TI  - Why I became an anaesthetist 

PMID- 9632437
TI  - Science and the retreat from reason 

PMID- 9632438
TI  - Wit and fizz: selected works of ruth holland 

PMID- 9632440
TI  - Long term hormone replacement therapy is needed to prevent hip fractures 

PMID- 9632439
TI  - Quality of care before admission to intensive care is often poor 

PMID- 9632442
TI  - Cell counts of bursal fluid provide a simple test for septic bursitis 

PMID- 9632441
TI  - Revised guidelines on advanced life support cover the use of automated
      defibrillators 

PMID- 9632443
TI  - Doctors may put patients off with antismoking advice 

PMID- 9632444
TI  - Outcomes in patients with acute non-Q-wave myocardial infarction randomly
      assigned to an invasive as compared with a conservative management strategy.
      Veterans Affairs Non-Q-Wave Infarction Strategies in Hospital (VANQWISH) Trial
      Investigators.
AB  - BACKGROUND: Non-Q-wave myocardial infarction is usually managed according to an
      "invasive" strategy (i.e., one of routine coronary angiography followed by
      myocardial revascularization). METHODS: We randomly assigned 920 patients to
      either "invasive" management (462 patients) or "conservative" management, defined
      as medical therapy and noninvasive testing, with subsequent invasive management
      if indicated by the development of spontaneous or inducible ischemia (458
      patients), within 72 hours of the onset of a non-Q-wave infarction. Death or
      nonfatal infarction made up the combined primary end point. RESULTS: During an
      average follow-up of 23 months, 152 events (80 deaths and 72 nonfatal
      infarctions) occurred in 138 patients who had been randomly assigned to the
      invasive strategy, and 139 events (59 deaths and 80 nonfatal infarctions) in 123
      patients assigned to the conservative strategy (P=0.35). Patients assigned to the
      invasive strategy had worse clinical outcomes during the first year of follow-up.
      The number of patients with one of the components of the primary end point (death
      or nonfatal myocardial infarction) and the number who died were significantly
      higher in the invasive-strategy group at hospital discharge (36 vs. 15 patients,
      P=0.004, for the primary end point; 21 vs. 6, P=0.007, for death), at one month
      (48 vs. 26, P=0.012; 23 vs. 9, P=0.021), and at one year (111 vs. 85, P=0.05; 58
      vs. 36, P= 0.025). Overall mortality during follow-up did not differ
      significantly between patients assigned to the conservative-strategy group and
      those assigned to the invasive-strategy group (hazard ratio, 0.72; 95 percent
      confidence interval, 0.51 to 1.01). CONCLUSIONS: Most patients with non-Q-wave
      myocardial infarction do not benefit from routine, early invasive management
      consisting of coronary angiography and revascularization. A conservative,
      ischemia-guided initial approach is both safe and effective.

PMID- 9632445
TI  - High risk of cerebral-vein thrombosis in carriers of a prothrombin-gene mutation
      and in users of oral contraceptives.
AB  - BACKGROUND: Idiopathic cerebral-vein thrombosis can cause serious neurologic
      disability. We evaluated risk factors for this disorder, including genetic risk
      factors (mutations in the genes encoding factor V and prothrombin) and nongenetic
      risk factors (such as the use of oral contraceptive agents). We compared the
      prevalence of these risk factors in 40 patients with cerebral-vein thrombosis, 80
      patients with deep-vein thrombosis of the lower extremities, and 120 healthy
      controls. The G1691A mutation in the factor V gene and the G20210A prothrombin
      gene mutation, which are established genetic risk factors for venous thrombosis,
      were studied. We also assessed the use of oral contraceptives and other risk
      factors for thrombosis. RESULTS: The prevalence of the prothrombin-gene mutation
      was higher in patients with cerebral-vein thrombosis (20 percent) than in healthy
      controls (3 percent; odds ratio, 10.2; 95 percent confidence interval, 2.3 to
      31.0) and was similar to that in patients with deep-vein thrombosis (18 percent).
      Similar results were obtained for the mutation in the factor V gene. The use of
      oral contraceptives was more frequent among women with cerebral-vein thrombosis
      (96 percent) than among controls (32 percent; odds ratio, 22.1; 95 percent
      confidence interval, 5.9 to 84.2) and among those with deep-vein thrombosis (61
      percent; odds ratio, 4.4; 95 percent confidence interval, 1.1 to 17.8). For women
      who were taking oral contraceptives and who also had the prothrombin-gene
      mutation (seven patients with cerebral-vein thrombosis but only one control), the
      odds ratio for cerebral-vein thrombosis rose to 149.3 (95 percent confidence
      interval, 31.0 to 711.0). CONCLUSIONS: Mutations in the prothrombin gene and the
      factor V gene are associated with cerebral-vein thrombosis. The use of oral
      contraceptives is also strongly and independently associated with the disorder.
      The presence of both the prothrombin-gene mutation and oral-contraceptive use
      raises the risk of cerebral-vein thrombosis further.

PMID- 9632446
TI  - Hyperfractionated irradiation with or without concurrent chemotherapy for locally
      advanced head and neck cancer.
AB  - BACKGROUND: Radiotherapy is often the primary treatment for advanced head and
      neck cancer, but the rates of locoregional recurrence are high and survival is
      poor. We investigated whether hyperfractionated irradiation plus concurrent
      chemotherapy (combined treatment) is superior to hyperfractionated irradiation
      alone. METHODS: Patients with advanced head and neck cancer who were treated only
      with hyperfractionated irradiation received 125 cGy twice daily, for a total of
      7500 cGy. Patients in the combined-treatment group received 125 cGy twice daily,
      for a total of 7000 cGy, and five days of treatment with 12 mg of cisplatin per
      square meter of body-surface area per day and 600 mg of fluorouracil per square
      meter per day during weeks 1 and 6 of irradiation. Two cycles of cisplatin and
      fluorouracil were given to most patients after the completion of radiotherapy.
      RESULTS: Of 122 patients who underwent randomization, 116 were included in the
      analysis. Most patients in both treatment groups had unresectable disease. The
      median follow-up was 41 months (range, 19 to 86). At three years the rate of
      overall survival was 55 percent in the combined-therapy group and 34 percent in
      the hyperfractionation group (P=0.07). The relapse-free survival rate was higher
      in the combined-treatment group (61 percent vs. 41 percent, P=0.08). The rate of
      locoregional control of disease at three years was 70 percent in the combined
      treatment group and 44 percent in the hyperfractionation group (P=0.01).
      Confluent mucositis developed in 77 percent and 75 percent of the two groups,
      respectively. Severe complications occurred in three patients in the
      hyperfractionation group and five patients in the combined-treatment group.
      CONCLUSIONS: Combined treatment for advanced head and neck cancer is more
      efficacious and not more toxic than hyperfractionated irradiation alone.

PMID- 9632448
TI  - Images in clinical medicine. "R-on-T" phenomenon.

PMID- 9632447
TI  - An experimental model of sudden death due to low-energy chest-wall impact
      (commotio cordis)
AB  - BACKGROUND: The syndrome of sudden death due to low-energy trauma to the chest
      wall (commotio cordis) has been described in young sports participants, but the
      mechanism is unknown. METHODS: We developed a swine model of commotio cordis in
      which a low-energy impact to the chest wall was produced by a wooden object the
      size and weight of a regulation baseball. This projectile was thrust at a
      velocity of 30 miles per hour and was timed to the cardiac cycle. RESULTS: We
      first studied 18 young pigs, 6 subjected to multiple chest impacts and 12 to
      single impacts. Of the 10 impacts occurring within the window from 30 to 15 msec
      before the peak of the T wave on the electrocardiogram, 9 produced ventricular
      fibrillation. Ventricular fibrillation was not produced by impacts at any other
      time during the cardiac cycle. Of the 10 impacts sustained during the QRS
      complex, 4 resulted in transient complete heart block. We also studied whether
      the use of safety baseballs, which are softer than standard ones, would reduce
      the risk of arrhythmia. A total of 48 additional animals sustained up to three
      impacts during the T-wave window of vulnerability to ventricular fibrillation
      with a regulation baseball and safety baseballs of three degrees of hardness. We
      found that the likelihood of ventricular fibrillation was proportional to the
      hardness of the ball, with the softest balls associated with the lowest risk (two
      instances of ventricular fibrillation after 26 impacts, as compared with eight
      instances after 23 impacts with regulation baseballs). CONCLUSIONS: This
      experimental model of commotio cordis closely resembles the clinical profile of
      this catastrophic event. Whether ventricular fibrillation occurred depended on
      the precise timing of the impact. Safety baseballs, as compared with regulation
      balls, may reduce the risk of commotio cordis.

PMID- 9632449
TI  - The role of T-cell costimulatory activation pathways in transplant rejection.

PMID- 9632450
TI  - Nonaccidental head injury in infants--the "shaken-baby syndrome".

PMID- 9632452
TI  - Use and overuse of angiography and revascularization for acute coronary
      syndromes.

PMID- 9632453
TI  - Venous thrombosis--the interaction of genes and environment.

PMID- 9632454
TI  - Fatal impact--concussion of the heart.

PMID- 9632455
TI  - Bitter pills to swallow.

PMID- 9632456
TI  - Enhanced preference for a protein-containing diet in response to dietary protein
      restriction.
AB  - Rats were maintained for 10 days on either a protein-free or a nutritionally
      complete maintenance diet, and they were also given access to protein-rich and
      carbohydrate-rich test diets during separate daily 2-h test sessions. In
      Experiment 1, rats maintained on the protein-free diet gradually and selectively
      increased their intake of the protein test diet, and eventually derived 16% of
      their daily energy intake from the protein test diet. Rats maintained on a
      nutritionally complete diet ate similar amounts of the two test diets even when
      their total caloric intake was matched to that of rats maintained on the protein
      free diet. In Experiment 2, rats that developed a preference for the protein test
      diet while maintained on a protein-free diet were given Purina Chow for 25 days
      to allow them to recover from their protein deficiency. When these rats were
      later returned to the protein-free diet for 10 days, their preference for the
      protein test diet was immediate and sustained. However, if they were maintained
      on the nutritionally complete diet after the 25-day recovery period, they
      initially preferred the protein test diet, but this preference diminished over
      days. Results of these studies are consistent with other findings showing that
      rats can learn to compensate for macronutrient deficiencies by using oral-sensory
      cues. In particular, the rats' diet selection was consistent with their having
      learned a preference for the cues paired with dietary protein.

PMID- 9632457
TI  - Circadian rhythms in the Zucker obese rat: assessment and intervention.
AB  - Body temperature (Tb) and activity were recorded by telemetry in obese and lean
      Zucker rats in light-dark (LD), constant dark (DD) and constant light (LL). In
      LD, obese rats, by comparison with lean rats, exhibited a 2-4-h phase advance and
      attenuated amplitude of Tb and activity rhythms. These differences persisted on
      the first day of DD, and thus were not due to differential sensitivity to masking
      effects of light. In LL, obese and lean rats exhibited similar free-running
      periods, thus the phase advance in LD was also not due to a short intrinsic
      period. In LD, obese rats exhibited more diurnal food intake and a reduced LD
      intake ratio. To assess the role of diurnal feeding in weight gain, one group of
      obese rats was fed ad libitum, and another fed only at night. Food intake did not
      differ significantly between groups, but ad libitum fed rats gained 23% more
      weight (60 g) over 60 days, suggesting that excessive diurnal feeding may
      contribute adversely to body weight regulation in this animal model of obesity.

PMID- 9632458
TI  - Effects of information about fat content on food preferences in pre-adolescent
      children.
AB  - The acceptance and sensory characteristics of standard and reduced-fat cookies
      were evaluated either with or without fat-content information by pre-adolescent
      children. Results indicate that acceptance ratings were not affected by the fat
      content or information about fat content when evaluated on nine-point scales.
      However, when asked to choose which cookie they liked better and to predict how
      many cookies they would eat (in forced-choice questions), fat content and
      information about fat content had a significant effect on cookie preference and
      prospective intake. When no information was available, subjects preferred the
      cookie with the higher fat content; when information was presented, subjects'
      preference shifted to the reduced-fat cookie. When asked which cookie they would
      choose to eat for dessert with hypothetical lunches, a similar shift in choice
      was observed following a low-fat lunch. The low-fat label was also associated
      with an increase in perceived healthiness relative to the high-fat label, as
      indicated on "good for me" scales. The effects of fat content information on
      cookie preference and prospective consumption were seen in pre-adolescents who
      indicated a "high concern" for the health consequences of dietary fat. Cookie
      preference and prospective intake of subjects who indicated a "low concern" were
      not affected by fat content labeling. Results suggest that fat content and
      information about fat content may affect food preference and intake in pre
      adolescent children.

PMID- 9632459
TI  - Infants' consumption of a new food enhances acceptance of similar foods.
AB  - The number of feedings needed to increase intake of a novel target food was
      investigated, and whether exposure effects generalized to other foods in a sample
      of 4 to 7-month-old infants (N=39). Other foods varied in their similarity to the
      target food, including the same food prepared by another manufacturer, similar
      foods (other fruits for infants receiving a target fruit) and a different food
      (e. g. vegetables for infants receiving a target fruit). Infants were fed the
      target food once a day for 10 days. Intake was used to indicate acceptance.
      Results revealed that exposure dramatically increased infants' intake of the
      target food, from an average of 35-72 g. Intake of the different food was
      unchanged. Same and similar food intake increased with target food exposure.
      Intake of the target, same and similar foods nearly doubled to 60 g after one
      exposure to the target food. These rapid increases in intake contrast the slower
      changes seen in young children. Results for the other foods suggest that infants
      may have difficulty discriminating among many foods.

PMID- 9632460
TI  - Infant salt preference and mother's morning sickness.
AB  - Evidence for an association between early pregnancy sickness and offspring salt
      (NaCl) preference has been obtained from studying offspring as young adults. To
      determine whether effects on NaCl preference are expressed in infancy, the
      present study examined 16-week-old infants whose mothers reported either little
      or no vomiting (N = 15) or frequent moderate to severe vomiting (N = 14) during
      the first 14 weeks of their pregnancy. The infants' oral-motor facial reactions
      to each solution and their relative intakes of distilled water and 0.1m and 0.2m
      NaCl were used as measures of preference. Infants of mothers who reported no or
      mild symptoms had a significantly lower relative intake of salt solutions than
      infants whose mothers reported moderate to severe symptoms (p < 0.01). The former
      infants also showed a greater number of aversive facial responses when given 0.2m
      NaCl (p < 0.05). Taken together, these findings support the hypothesis that
      maternal dehydration, induced by moderate to severe vomiting during pregnancy,
      can lead to enhanced salt preference in offspring. They also provide a potential
      explanation for some of the variability encountered when human infants are tested
      for their salt preference.

PMID- 9632461
TI  - Is pleasantness of biscuits and cakes related to their actual or to their
      perceived sugar and fat contents?
AB  - Perceptions of sugar, fat and moisture contents, as well as their influences on
      pleasantness were investigated in commercial foods. One-hundred-and-two-normal
      weight men rated the "pleasantness", "flavour intensity", "moisture", "sweetness"
      and "fatness" of 39 different biscuits and cakes. Sugar content was accurately
      perceived up to a maximum content of about 33% weight/weight. The perception of
      fat content was less accurate and depended on both fat and sugar contents. High
      sugar contents seemed to decrease perception of fatness. Pleasantness was
      influenced mainly by sugar content and less by fat content. Pleasantness was
      better predicted by rated contents than by actual contents; it was even better
      predicted by the overall flavour intensity. Preferences for high fat stimuli did
      not appear to be based on conscious perception of their fat content. We conclude
      that the classical results obtained with simple experimental stimuli remain
      valid, as a first approximation, for commercial biscuits and cakes, despite their
      complex sensory characteristics.

PMID- 9632462
TI  - Influence of PROP-sensitivity on taste perceptions and hedonics in French women.
      A study performed without retronasal olfaction.
AB  - Detection threshold for the taste of PROP (6-n-propyl thiouracil) in aqueous
      solution was determined in 173 French Caucasian women deprived of retronasal
      olfaction by blowing an air stream into the nostrils. As expected, the detection
      thresholds were bimodally distributed, although as many as 73% of the subjects
      had thresholds above the antimode concentration and therefore qualified as non
      tasters. Detection threshold, difference threshold, intensity perceptions and
      preference ratings were then determined for NaCl, sucrose, caffeine, Na saccharin
      and naringin in 20 tasters and 20 non-tasters. No differences were found between
      tasters and non-tasters for detection or difference thresholds of the various
      tastants. Intensity and preference ratings for solutions of NaCl, saccharin or
      caffeine were not influenced by taster status. Although ratings of sweetness
      intensity for sucrose solutions did not differ between tasters and non-tasters,
      concentrated sucrose solutions were more disliked by non-tasters than by tasters.
      Non-tasters rated naringin solutions as more bitter than tasters, but naringin
      preference ratings were independent of taster status. Some of these findings were
      unexpected and further studies are required to find out whether they stem from
      the odour-preventing procedure or are of biological or cultural origin.

PMID- 9632465
TI  - Volume contents and index 

PMID- 9632466
TI  - Teat massage after milk ingestion in domestic piglets: an example of honest
      begging?
AB  - After milk ejection, piglets spend several minutes massaging their own teats on
      the sow. We examined whether this behaviour could be a mammalian counterpart to
      begging in young birds, and hence be explained by theories of honest begging. In
      one experiment, the behaviour of piglets was examined in relation to their
      previous milk intake. In each of 16 litters, one focal piglet was exposed to
      three treatments for three consecutive sucklings: 'no milk', where the piglet was
      withheld from the teat during milk ejection; 'extra milk', where it was fed 10 ml
      of extra milk directly after milk ejection; and 'control', when it received its
      normal intake. Average massage duration in the next three sucklings was
      significantly longer in the 'no milk' than in the control piglets. 'No milk' pigs
      massaged more intensely (number of massage movements/min), were more persistent
      in attempting to maintain udder contact and spent less time away from the udder.
      However, there were no significant differences between 'control' and 'extra milk'
      treatments. In a second experiment, in which we manually massaged teats for 0, 3
      or 10 min, we found no significant effect of massage duration on milk output
      (measured by weighing piglets before and after milk ejection), although massage
      tended to increase output. We conclude that post-sucking massage in piglets has a
      number of aspects similar to honest begging in birds. Copyright 1998 The
      Association for the Study of Animal Behaviour. Copyright 1998 The Association for
      the Study of Animal Behaviour.

PMID- 9632463
TI  - The physiology of motivation revisited.

PMID- 9632467
TI  - Path integration in dogs.
AB  - We studied path integration in dogs, Canis familiaris, required to return to the
      starting point of L-shaped outward paths in the absence of landmark information.
      The analysis of the distributions of errors in the return direction and distance
      showed that the dogs made both systematic and random errors. They tended to
      overestimate by about 6 degrees the amount of turning required at the end of the
      outward path to take the correct return direction. Random angular errors were
      characterized by a standard deviation of about 9 degrees. The dogs also tended to
      underestimate the correct return distance by about 6%, and random distance errors
      were characterized by a standard deviation of about 13% of the correct return
      distance. While random errors are assumed to stem simply from inaccuracies in
      kinaesthetic and vestibular systems, systematic errors are likely to be generated
      because path integration is implemented at the neural level through approximate
      rather than mathematically exact solutions. A path integration model in which the
      moving animal is assumed to overestimate slightly the inferred motion parallax of
      the starting point can roughly account for the dogs' directional bias, but not
      for systematic errors in distance estimation. Copyright 1998 The Association for
      the Study of Animal Behaviour. Copyright 1998 The Association for the Study of
      Animal Behaviour.

PMID- 9632468
TI  - Barbary macaques categorize shrill barks into two call types.
AB  - In response to disturbances in their surroundings, Barbary macaques, Macaca
      sylvanus, utter a distinctive call, the 'shrill bark'. Differences within this
      call type correlate with the stimulus eliciting the calling. I tested whether
      monkeys categorized calls according to the eliciting stimulus and whether their
      perception of calls coincided with the classification derived from the acoustic
      analysis. Different playback designs using the habituation-dishabituation
      paradigm were created in which calls exhibiting varying degrees of acoustic
      difference were paired. I conducted experiments in two populations of semi-free
      ranging Barbary macaques. The results suggest that subjects categorized calls
      according to the eliciting stimulus. In addition, subjects from the population in
      which the recordings were made were significantly better than subjects from the
      other population at discriminating between calls with small acoustic differences.
      The results suggest that call categorization is influenced by experience,
      mediated by individual knowledge of the caller or common call characteristics
      within the population. Copyright 1998 The Association for the Study of Animal
      Behaviour. Copyright 1998 The Association for the Study of Animal Behaviour.

PMID- 9632469
TI  - Differences in begging behaviour between barn swallow, Hirundo rustica,
      nestlings.
AB  - Recent models of parent-offspring communication suggest that nestling begging
      reliably reflects food requirements, and therefore should increase with nestling
      need. Need may be affected by short-term variations in hunger, as well as by long
      term factors such as relative size, growth rate and body condition. In the
      present study, the brood sizes of barn swallows were manipulated to create
      differences in nestling growth rate and body condition. The extent to which
      begging behaviour reflects these differences was tested. I measured begging
      behaviour by removing nestlings from the nest for three laboratory tests in which
      temporal variations in hunger were controlled, and four target nestlings (small
      and large, from small and large broods) were tested simultaneously. Small
      nestlings and nestlings from large broods had lower growth rates and poorer body
      condition than large nestlings and nestlings from small broods, respectively.
      Begging was positively correlated with both short- and long-term determinants of
      need. However, when nestlings grew older (second test), the trend was mixed,
      mainly because begging levels dropped in the neediest nestling category (small
      nestlings from large broods). After nestlings had been exchanged between broods
      for 24 h, small nestlings from large broods improved their growth rate and body
      condition, but still begged less than expected from their long-term need. The
      results suggest that nestling begging strategies vary with brood size and with
      nestling rank. However, these variations may reflect not only long-term need, but
      also nestling response to past experience or to variations in the cost and
      effectiveness of their begging efforts. Copyright 1998 The Association for the
      Study of Animal Behaviour. Copyright 1998 The Association for the Study of Animal
      Behaviour.

PMID- 9632470
TI  - Parasites and flower choice of bumblebees.
AB  - In a field experiment, we tested whether workers of bumblebees, Bombus pascuorum
      and B. humilis, parasitized by larvae of conopid flies, Physocephala rufipes and
      Sicus ferrugineus, differ in their flower choice from unparasitized ones. We
      collected workers at random in the field and immediately tested them in
      experimental arenas that offered the choice of a reference plant (red clover,
      Trifolium pratense) versus a test plant (from five species). The choices of 396
      workers were analysed with logistic regression models (logit analysis). We
      performed all tests in the same field and at the same time where the workers were
      foraging naturally. On average, the parasitized bees were less likely to visit
      the reference plant. In addition, they were more likely to switch plant species
      even after the first visit in the experimental sequence. Copyright 1998 The
      Association for the Study of Animal Behaviour. Copyright 1998 The Association for
      the Study of Animal Behaviour.

PMID- 9632471
TI  - Finding a dominance order most consistent with a linear hierarchy: a new
      procedure and review.
AB  - A procedure for ordering a set of individuals into a linear or near-linear
      dominance hierarchy is presented. Two criteria are used in a prioritized way in
      reorganizing the dominance matrix to find an order that is most consistent with a
      linear hierarchy: first, minimization of the numbers of inconsistencies and,
      second, minimization of the total strength of the inconsistencies. The linear
      ordering procedure, which involves an iterative algorithm based on a generalized
      swapping rule, is feasible for matrices of up to 80 individuals. The procedure
      can be applied to any dominance matrix, since it does not make any assumptions
      about the form of the probabilities of winning and losing. The only assumption is
      the existence of a linear or near-linear hierarchy which can be verified by means
      of a linearity test. A review of existing ranking methods is presented and these
      are compared with the proposed method. Copyright 1998 The Association for the
      Study of Animal Behaviour. Copyright 1998 The Association for the Study of Animal
      Behaviour.

PMID- 9632472
TI  - Certainty of paternity and paternal investment in eastern bluebirds and tree
      swallows.
AB  - Extra-pair paternity is common in many socially monogamous passerine birds with
      biparental care. Thus, males often invest in offspring to which they are not
      related. Models of optimal parental investment predict that, under certain
      assumptions, males should lower their investment in response to reduced certainty
      of paternity. We attempted to reduce certainty of paternity experimentally in two
      species, the eastern bluebird, Sialia sialis, and the tree swallow, Tachycineta
      bicolor, by temporarily removing fertile females on two mornings during egg
      laying. In both species, experimental males usually attempted to copulate with
      the female immediately after her reappearance, suggesting that they experienced
      the absence of their mate as a threat to their paternity. Experimental males
      copulated at a significantly higher rate than control males. However, contrary to
      the prediction of the model, experimental males did not invest less than control
      males in their offspring. There was no difference between experimental and
      control nests in the proportion of male feeds, male and female feeding rates,
      nestling growth and nestling condition and size at age 14 days. We argue that
      females might have restored the males' confidence in paternity after the
      experiment by soliciting or accepting copulations. Alternatively, males may not
      reduce their effort, because the fitness costs to their own offspring may
      outweigh the benefits for the males, at least in populations where females cannot
      fully compensate for reduced male investment. Copyright 1998 The Association for
      the Study of Animal Behaviour. Copyright 1998 The Association for the Study of
      Animal Behaviour.

PMID- 9632473
TI  - The effect of quality and availability of foraging materials on feather pecking
      in laying hen chicks.
AB  - Feather pecking resulting in feather damage, injuries and mortality causes severe
      welfare problems in laying hens. In the present study, we tested whether there is
      an inverse relationship between feather pecking and foraging behaviour
      (exploratory and manipulative behaviour away from the feeder). Forty-eight groups
      of 30 or 31 chicks, Gallus gallus domesticus, were reared in pens and provided
      with different types of foraging material. Feather pecking and foraging behaviour
      were quantified when the chicks were 4 and 5 weeks of age. In experiment 1,
      chicks with access to long-cut straw showed more foraging behaviour and less
      feather pecking than chicks that were provided with the same straw but in
      shredded form. On the other hand, there was no difference in foraging behaviour
      and feather pecking between chicks reared with access to long-cut straw and
      polystyrene blocks. In experiment 2, the importance of the form of the foraging
      material was confirmed. Chicks provided with polystyrene blocks performed more
      foraging behaviour and less feather pecking than chicks with access to
      polystyrene beads. The provision of an area with a layer of wood-shavings to
      promote scratching behaviour had no significant effect, however, on the incidence
      of feather pecking. In experiment 3, polystyrene blocks and beads were offered
      during the whole day or only in the morning. Both the quality and the
      availability of the foraging materials had a significant effect on foraging
      behaviour and a significant but opposite effect on feather pecking. Focal animal
      observations showed that the chicks performed different types of foraging
      behaviour at polystyrene blocks and beads. This suggests that not only the
      quantity but also the quality of foraging behaviour elicited by a given material
      may be important to prevent the development of feather pecking. Feather pecking
      should thus be considered as redirected foraging behaviour. Copyright 1998 The
      Association for the Study of Animal Behaviour. Copyright 1998 The Association for
      the Study of Animal Behaviour.

PMID- 9632474
TI  - Proximate costs of fighting in male cichlid fish: the role of injuries and energy
      metabolism.
AB  - While much is known about the functional significance of strategic decisions in
      animal fighting, relatively little is understood about the mechanisms that
      underlie the making of those decisions. In mechanistic terms, strategic
      decisions, such as either escalating a fight or giving up, are made in relation
      to the proximate costs that opponents inflict (or can potentially inflict) upon
      one another. These costs include physical injury and also the physiological
      consequences of engaging in an energetically demanding activity. We studied the
      role of injury and energy metabolism during fights between male cichlid fish,
      Tilapia zillii. In relation to injuries incurred during fights, scale loss
      differed depending on whether the winner was smaller or larger than its opponent;
      smaller winners inflicted significantly more damage on their opponents than they
      received, whereas this difference was not apparent in those fights won by the
      larger fish. In relation to energy metabolism, escalated fighting resulted in a
      significant depletion of total sugar reserves in the muscle and the liver. It
      appears that the muscle energy reserves are respired anaerobically, as was
      evident from the accumulation of lactate in the muscle. Losers had significantly
      higher levels of muscle lactate than winners. Together, the injury data and the
      metabolic data suggest that escalated fighting is costly for both winners and
      losers, but especially so for losers. These data are discussed in relation to
      models of animal decision making and we conclude that the difference between
      opponents in the proximate costs incurred during fighting is likely to underlie
      the making of decisions such as continuing, giving up or escalating the fight.
      Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1998
      The Association for the Study of Animal Behaviour.

PMID- 9632475
TI  - Fighting and assessment in male cichlid fish: the effects of asymmetries in
      gonadal state and body size.
AB  - In fights between animals over limited resources, the larger contestant often
      wins. Game theoretical models of animal fighting predict that relative body size
      is assessed during the fight and thus determines fight duration and intensity. In
      addition, if the contestants differ in the value they place on the disputed
      resource, this can also influence the outcome, duration and intensity of the
      fight. We studied territorial fighting in a cichlid fish, Tilapia zillii, in
      relation to relative body size and gonad weight. Relative gonad weight was a much
      stronger predictor of fight outcome than relative body size, even when body
      weight asymmetries were as large as 30%. This suggested that males with large
      gonads were fighting harder to defend their territory, perhaps because the value
      of a territory correlates with the gonadal state of the individual. A detailed
      analysis of mouth wrestling observed during fighting suggested that relative body
      size is assessed. However, contestants smaller than their opponent often
      continued to fight in spite of their size disadvantage. Weight disadvantaged
      winners appeared to fight more fiercely as suggested by a negative correlation
      between weight asymmetry and the proportion of bites inflicted by the winner.
      During escalated fighting, winners and losers differed consistently with regard
      to a behaviour termed mouth locking. Although neither biting nor persistence in
      mouth locking was related to gonad weight, we propose that the fish may have been
      assessing asymmetries unrelated to relative body size and possibly more related
      to levels of cost and the motivation to persist. Copyright 1998 The Association
      for the Study of Animal Behaviour. Copyright 1998 The Association for the Study
      of Animal Behaviour.

PMID- 9632476
TI  - Evolution of mate-choice copying: a dynamic model.
AB  - Mate-choice copying has recently been demonstrated in several species. Two, not
      mutually exclusive, explanations for copying have been proposed: it reduces
      sampling costs and/or error of mate choice. In guppies, Poecilia reticulata, and
      black grouse, Tetrao tetrix, young females seem most likely to copy. Therefore,
      copying may teach inexperienced females what attractive males look like. I
      developed a 2-year dynamic model, to investigate under which conditions a mate
      copying strategy might first evolve. An original population of pure choosers was
      assumed, which was invaded by a mutant female, able to copy during her first
      mating season, thereby instantly improving her ability to assess male quality.
      Alternatively, she could either wait and learn by observing males, just as non
      copiers may do, but incurring some time costs, or choose, relying on her own
      abilities. The degree to which copying occurred among these mutant, young,
      inexperienced females increased with an increasing proportion of old, experienced
      females in the population, and with decreasing time left until the end of the
      season. The model demonstrates that mate-choice copying may evolve, when young
      females are poor at discrimination and need to learn what high-quality males look
      like. Male quality proved to be unimportant for copying to evolve, as long as
      there are sufficient differences in quality for mate choice to be meaningful. As
      with previous models, time constraints are an important assumption for copying to
      be advantageous over non-copying. Copyright 1998 The Association for the Study of
      Animal Behaviour. Copyright 1998 The Association for the Study of Animal
      Behaviour.

PMID- 9632477
TI  - Energetic cost of sexual attractiveness: ultrasonic advertisement in wax moths.
AB  - Pair formation in the lesser wax moth, Achroia grisella (Lepidoptera: Pyralidae),
      is initiated by male ultrasonic signals that attract receptive females.
      Individual males vary in attractiveness to females, and the most attractive males
      are distinguished by exaggeration of three signal characters: pulse rate, peak
      amplitude and asynchrony interval (temporal separation between pulses generated
      by movements of the left and right wings during a given wing upstroke or
      downstroke). Using flow-through respirometry, we measured the resting and
      signalling metabolic rates of males whose relative attractiveness was known.
      Acoustic recordings and metabolic measurements were made simultaneously, and we
      calculated net metabolic rates and factorial metabolic scopes as measures for the
      energetic cost of signalling. On average, attractive males had higher net
      metabolic rates and factorial metabolic scopes than unattractive ones, but many
      unattractive males also had high values. Thus, high expenditure of energy on
      signalling is necessary but not sufficient for attractiveness. This may result
      because only one of the three signal characters critical for female preference,
      pulse rate, is correlated with energy expenditure. Although the results are
      consistent with the good genes model of sexual selection, they do not conflict
      with other indirect or direct mechanisms of female choice. Copyright 1998 The
      Association for the Study of Animal Behaviour. Copyright 1998 The Association for
      the Study of Animal Behaviour.

PMID- 9632478
TI  - No relationship between territory size and the risk of cuckoldry in birds.
AB  - It has been suggested that male birds adjust their territory size in order to
      prevent potential intruders from gaining extra-pair copulations. The risk of
      cuckoldry is supposed to be highest when the distance between a female and the
      neighbouring males is shortest. This paper describes the variation in territory
      size of the chiffchaff, Phylloscopus collybita, in relation to the breeding
      cycle. Contrary to the risk of cuckoldry hypothesis, chiffchaff territories were
      larger prior to the fertile period of the females and at a minimal size during
      the fertile period. A review of the literature shows little, if any, evidence of
      a peak in territory size during the fertile period of the females for most
      species studied. It is suggested that territoriality is in need of an operational
      definition. Without such a definition, it is difficult to make and test
      predictions about the adaptive basis of variation in territory size. Copyright
      1998 The Association for the Study of Animal Behaviour. Copyright 1998 The
      Association for the Study of Animal Behaviour.

PMID- 9632479
TI  - Parent-offspring recognition in thick-billed murres (Aves: Alcidae).
AB  - Using field experiments, we investigated the development of parent-offspring
      recognition in the thick-billed murre, Uria lomvia. Cross-fostering experiments
      (N=73) showed that the likelihood of parents accepting a foreign chick decreased
      with chick age. Simultaneous-choice playback experiments demonstrated that chicks
      discriminate between the calls of their parents and both strange and familiar
      adult conspecifics from as early as 3 days old. In presentation experiments with
      chicks of fledging age (>/=14 days), adults responded more strongly to the calls
      of their own chicks than to other familiar chicks from the same breeding ledge.
      Results are consistent with those of earlier studies of parent-offspring
      recognition in the congeneric and ecologically similar common murre, U. aalge,
      which were among the first to suggest that parent birds and their chicks can
      identify each other's calls. Copyright 1998 The Association for the Study of
      Animal Behaviour. Copyright 1998 The Association for the Study of Animal
      Behaviour.

PMID- 9632480
TI  - Song learning and vocal tradition in Nuttall's white-crowned sparrows.
AB  - We investigated song sharing and dispersion of song types in the wild in a colour
      marked population of the non-migratory Nuttall's white-crowned sparrow,
      Zonotrichia leucophrys nuttalli. The songs of fathers, their male progeny (sons),
      and the neighbours of the sons at recruitment sites were analysed
      spectrographically and compared qualitatively and quantitatively. To determine
      whether a son's song more closely matched that of his father or a neighbour at
      the site settled, we subjected frequency and temporal characteristics of songs
      within each father-son-neighbour triad to multivariate cluster analysis. The
      songs of 14 of 16 sons clustered with their neighbours' rather than their
      fathers' songs, confirming that song matching of neighbours is an integral
      component of territory settlement by juveniles. Principal components analysis of
      frequency and temporal measurements of song within a dialectal area show that
      songs group into neighbourhoods and are non-randomly distributed. Multivariate
      analysis suggests that sons may entrain on frequency and temporal characteristics
      of a neighbour's song without matching phrases or complex syllables. Implications
      for models of instructive versus selective learning are discussed. The timing of
      closure of the sensitive phase, the length of the silent interval between the
      sensory phase and plastic song stage, and the time to song crystallization remain
      open questions in song ontogeny. Copyright 1998 The Association for the Study of
      Animal Behaviour. Copyright 1998 The Association for the Study of Animal
      Behaviour.

PMID- 9632481
TI  - Behavioural correlates of testosterone and seasonal changes of steroids in red
      winged blackbirds.
AB  - I studied the relationship between behaviour and plasma testosterone level (T)
      and the seasonal changes in T and plasma corticosterone levels (B) in male red
      winged blackbirds, Agelaius phoeniceus. I measured T and B using
      radioimmunoassay, and on the day after taking blood, I observed each male's
      behaviour for 60 min. The time that males spent conspicuously perched and the
      number of songs were positively correlated with T, but the proportion of time
      spent conspicuously perched and the frequency of song were not correlated with T.
      The frequency of aggressive encounters, sexual chases, epaulet exposure when
      singing and flights within the territory were positively correlated with T,
      suggesting a direct role for circulating testosterone influencing male aggressive
      behaviour. Both T and B increased early in the breeding season, peaked when the
      first females were receptive, and decreased through the remainder of the breeding
      season. Late in the season, the presence of a receptive female caused males to
      have increased T. The peak in T when the first females were receptive, the
      positive correlation between aggression and T, and the response to a receptive
      female with increased T support predictions of the challenge hypothesis. T was
      positively correlated with B, suggesting a cost to the males of maintaining high
      T. When a receptive female was present on the male's territory, T was negatively
      correlated with date. Male red-winged blackbirds in Indiana may respond less to
      receptive females late in the season when benefits associated with protecting
      paternity and gaining extra-pair fertilizations decrease.Copyright 1998 The
      Association for the Study of Animal Behaviour. Copyright 1998 The Association for
      the Study of Animal Behaviour.

PMID- 9632482
TI  - Determinants of the longevity of socially learned food preferences of Norway
      rats.
AB  - We conducted three experiments to examine variables that might influence the
      longevity of socially induced food preferences in Norway rats. The duration of
      social influence on the food choices of 42-day-old rats (1) increased with both
      increasing numbers of demonstrators and increasing numbers of demonstrations by a
      single demonstrator, (2) varied with the temporal distribution of demonstrations,
      but (3) did not vary with the age of demonstrators. The results suggest that a
      single episode of social learning produces short-term, but not long-term, effects
      on a Norway rat's food choices. Copyright 1998 The Association for the Study of
      Animal Behaviour. Copyright 1998 The Association for the Study of Animal
      Behaviour.

PMID- 9632483
TI  - Sexual selection and the evolution of mechanical sound production in manakins
      (Aves: Pipridae).
AB  - I surveyed and described modulated, non-vocal, mechanical sounds of the lek
      breeding Neotropical manakins (Pipridae). Variation among manakin species in
      mechanical sound production, repertoire size, acoustic structure, associated
      feather specialization, and mechanical sound production mechanisms were analysed
      comparatively in the context of a phylogenetic hypothesis for the family.
      Mechanical sound production has probably evolved five or six times independently
      and been lost once within the 42 species of manakins. Complex mechanical sound
      repertoires have also evolved independently several times. Acoustic structure of
      these sounds indicates that at least four different physical mechanisms of
      mechanical sound production have evolved: short, broad-frequency spectrum pulses;
      short, low-frequency pulses; aerodynamic vortices; and harmonic oscillations. All
      well-known mechanical sounds in manakins are associated with obvious wing
      movements and sexually dimorphic wing feather specializations. Both primary and
      secondary wing feather specializations have evolved convergently within the
      family for the production of short, broad-frequency mechanical sound pulses. Two
      less well-known manakin clades also have tail feather specializations that may
      function in mechanical sound production. A concentrated-changes test documented
      that the dynamic patterns of evolution in mechanical sound production in the
      polygynous manakins are highly unlikely by chance alone. Intersexual selection
      for acrobatic display may have created subsequent opportunities for the evolution
      of novel preferences for incidental non-vocal sounds produced by acrobatic
      movements. Novel female preferences for these mechanical sounds led to further
      elaboration of these sounds and to the evolution of complex mechanical sound
      repertoires in independent lineages of the family. Copyright 1998 The Association
      for the Study of Animal Behaviour. Copyright 1998 The Association for the Study
      of Animal Behaviour.

PMID- 9632484
TI  - Sex-role reversal and the absence of extra-pair fertilization in Wilson's
      phalaropes.
AB  - Extra-pair fertilizations are common in birds, which has led to great interest in
      how this phenomenon is regulated at a proximate level and how extra-pair
      fertilizations, and extra-pair fertilization avoidance, shape avian social
      systems. In Wilson's phalaropes, Phalaropus tricolor, incubation and brood
      rearing is performed exclusively by males. Males are able to rear only a single
      brood of four during a breeding season. This suggests that males have a high
      level of paternity in clutches and broods under their care and, thus, that extra
      pair fertilizations are infrequent. In contrast, female social dominance, lack of
      territoriality and frequent interactions among breeding adults suggest that both
      males and females have the opportunity to engage in extra-pair copulations. Using
      DNA fingerprint band-sharing between putative parents and offspring, we found no
      evidence of extra-pair fertilizations among 51 offspring from 17 families of
      phalaropes. Copulation disruption by non-copulatory adults, ability of females to
      reject copulation attempts and potential fitness benefits to females by avoiding
      extra-pair fertilizations were sufficient to explain the absence of extra-pair
      fertilizations in Wilson's phalaropes. We propose that sex-role reversal affects
      the relative costs and benefits to females of seeking extra-pair fertilizations.
      At the time of clutch completion, females have invested particularly heavily in
      their clutches due to intense competition among females to gain and keep a mate
      during the pre-laying and laying periods. After clutch completion, nest success
      requires significant male parental care. Benefits to females in gaining extra
      pair fertilizations may be offset by the risk of losing male parental care.
      Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1998
      The Association for the Study of Animal Behaviour.

PMID- 9632485
TI  - Context determines the sex appeal of male zebra finch song.
AB  - We explored the conditions under which playbacks of male zebra finch, Taeniopygia
      guttata, song induced reproduction in females. In a laboratory study, a rise in
      faecal oestrogen levels predicted egg laying. Song playbacks by themselves
      induced a decrease in oestrogen levels. There was an increase in oestrogen
      levels, followed by egg laying, when the song was broadcast from inside a male
      model positioned away from the nest. However, this effect occurred only when a
      second, silent male model was perched on the rim of the nest. If song was
      broadcast from inside the model perched on the nest, there was no increase in
      oestrogen levels. We conclude that tests of song efficacy in female songbirds
      must respect some contextual rules, which are likely to vary between species.
      Only then does it become possible to ascertain which sounds are most effective in
      inducing physiological changes leading to reproduction. Copyright 1998 The
      Association for the Study of Animal Behaviour. Copyright 1998 The Association for
      the Study of Animal Behaviour.

PMID- 9632486
TI  - Lifetime mating opportunities and male mating behaviour in sexually cannibalistic
      praying mantids.
AB  - I examined the number of lifetime mating opportunities and mating behaviour of
      males in two sexually cannibalistic species, the Mediterranean, Iris oratoria,
      and bordered, Stagmomantis limbata, praying mantids (Mantodea: Mantidae). Two
      approaches estimated the number of lifetime mating opportunities: direct
      observations of intersexual encounters in the field, and an encounter model. I
      collected behavioural observations, together with ecological data for use in the
      model, over three field seasons. The ecological data included an assessment of
      the feeding condition of S. limbata females in nature; the females fed at a level
      comparable to females maintained on an abundant diet in the laboratory. As for
      the number of mating opportunities, individual males of both species encountered
      two or more females, as predicted by the model. I observed no male, however, in
      more than one copulation. This result could reflect individual variation in the
      times and places of sexual activity or an actual low number of mating
      opportunities in the field. Furthermore, a higher percentage of I. oratoria males
      encountered two or more females than S. limbata males, as the model indicates.
      Fewer mating opportunities could lead to greater selection upon S. limbata males
      to ensure paternity at each mating, which can explain the longer copulation times
      observed for S. limbata males. I considered two hypotheses about male behaviour
      in light of the number of lifetime encounters with females: male suicide and male
      reduction of the risk of cannibalism. Behavioural observations do not strongly
      support male suicide in either species. Certain male behaviours, such as the
      nature of copulatory position and, in captivity, mounting females from the rear,
      are consistent with the idea that males behave so as to reduce the probability
      that they are cannibalized during intersexual encounters. Moreover, male I.
      oratoria preferentially mount well-fed, fecund females in captivity. Taken
      together, these results suggest that the prospect of multiple mating
      opportunities has influenced male mating behaviour over evolutionary time.
      Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1998
      The Association for the Study of Animal Behaviour.

PMID- 9632487
TI  - Measuring female mating preferences.
AB  - Interest in the evolution of female mating preferences has increased greatly in
      recent years, and numerous hypotheses have been proposed to explain how mating
      preferences evolve. Despite this interest, little is known about how selection
      acts on mating preferences in natural populations. One reason for this lack of
      information may be that experimental designs commonly used for testing female
      preferences make it difficult to quantify the preferences of individual females.
      Most commonly used designs share three features: they examine the preferences of
      populations of females, they test female responses when they are presented
      simultaneously with two stimuli, and they infer information on female preferences
      by observing female choices between alternative stimuli. Population-level choice
      tests, in which each female is tested only once with a set of stimuli, do not
      evaluate within-female variation in preference, which is necessary to document
      between-female variation in preference. Two-stimulus designs test only for
      directional preferences if female responses are tested with only a single pair of
      stimuli. In addition, dichotomous scoring of female responses makes detection of
      between-female variation in preference difficult. Simultaneous stimulus
      presentations can confound female preference and female sampling behaviour. An
      alternative method to assess female preferences is to measure repeatedly the
      preference functions of individual females using a single-stimulus design. The
      shape of a female's preference function indicates how a female's mating response
      varies with male trait value, and repeated measures of individual preference
      functions allow measurement of within- and between-female variation in
      preferences. Copyright 1998 The Association for the Study of Animal Behaviour.
      Copyright 1998 The Association for the Study of Animal Behaviour.

PMID- 9632488
TI  - The onset of incubation in birds: can females control hatching patterns?
AB  - We investigated intraspecific variation in incubation behaviour of wild Eurasian
      kestrels, Falco tinnunculus, in Finland and tested whether patterns of hatching
      asynchrony could be predicted from patterns of incubation. The timing of the
      onset of incubation varied considerably for 17 female kestrels. Eggs generally
      hatched in the order they were laid, and both total hatching span of the clutch
      and the pattern of eggs hatching on certain days corresponded well with
      incubation behaviour. This result was consistent with the idea that females have
      much control over hatching patterns. In the majority (65%) of cases, the
      proportion of daily incubation increased monotonically with the laying sequence,
      a pattern described previously in other birds. Unusual patterns of incubation
      (35%) were most common in females with poor body condition during incubation and
      may be the result of energy constraints during laying.Copyright 1998 The
      Association for the Study of Animal Behaviour. Copyright 1998 The Association for
      the Study of Animal Behaviour.

PMID- 9632489
TI  - The relative cost of children's physical play.
AB  - There has been a long-standing debate regarding the functions of play during
      childhood. An important, but neglected, first step in this debate entails
      documenting the costs associated with play. In this study we analysed energetic
      costs (expressed in terms of caloric expenditure) associated with physical play
      in four field experiments of play in primary school children. Experiment 1
      established the concurrent validity of an observational check list to estimate
      caloric expenditure of children's physical play. Experiment 2 compared caloric
      expenditure of the play (defined as all behaviour exhibited during play time) for
      two age groups of children during playtime outdoors and during indoor sedentary
      activity; caloric expenditure of outdoor activity was greater and was
      significantly correlated with ambient temperature. In experiment 3, children were
      observed during indoor play to control for the influence of ambient temperature.
      Outdoor physical play was more energetically costly than indoor physical play. In
      experiment 4, children's behaviour was observed outdoors and caloric expenditure
      for play, games and other activities was compared. Physical play was more costly
      than other forms of behaviour and games. Estimates of total energetic costs of
      play ranged from 6 to 15%. Results are discussed in terms of the relatively low
      caloric costs of play. Copyright 1998 The Association for the Study of Animal
      Behaviour. Copyright 1998 The Association for the Study of Animal Behaviour.

PMID- 9632491
TI  - A demanding task: using economic techniques to assess animal priorities.
AB  - Copyright 1998 The Association for the Study of Animal Behaviour.

PMID- 9632490
TI  - Five primate species follow the visual gaze of conspecifics.
AB  - Individuals from five primate species were tested experimentally for their
      ability to follow the visual gaze of conspecifics to an outside object. Subjects
      were from captive social groups of chimpanzees, Pan troglodytes, sooty mangabeys,
      Cercocebus atys torquatus, rhesus macaques, Macaca mulatta, stumptail macaques,
      M. arctoides, and pigtail macaques, M. nemestrina. Experimental trials consisted
      of an experimenter inducing one individual to look at food being displayed, and
      then observing the reaction of another individual (the subject) that was looking
      at that individual (not the food). Control trials consisted of an experimenter
      displaying the food in an identical manner when the subject was alone.
      Individuals from all species reliably followed the gaze of conspecifics, looking
      to the food about 80% of the time in experimental trials, compared with about 20%
      of the time in control trials. Results are discussed in terms of both the
      proximate mechanisms that might be involved and the adaptive functions that might
      be served by gaze-following. Copyright 1998 The Association for the Study of
      Animal Behaviour. Copyright 1998 The Association for the Study of Animal
      Behaviour.

PMID- 9632492
TI  - Using economic techniques to assess animal priorities: repays the investment.
AB  - Copyright 1998 The Assocation for the Study of Animal Behaviour.

PMID- 9632493
TI  - A demanding task: using economic techniques to assess animal priorities. A reply
      to Mason et al.
AB  - Copyright 1998 The Association for the study of Animal Behaviour.

PMID- 9632494
TI  - Assessing animal priorities: future directions.
AB  - Copyright 1998 The Association for the Study of Animal Behaviour..

PMID- 9632495
TI  - Editorial.
AB  - Copyright 1998 The Association for the Study of Animal Behaviour.

PMID- 9632496
TI  - Functional equivalence in a California sea lion: relevance to animal social and
      communicative interactions.
AB  - Laboratory investigations into equivalence class formation suggest how animals in
      social and communicative contexts learn to place dissimilar individuals, signals,
      responses and social reinforcers into the same functional class. Kastak &
      Schusterman (1994, Anim. Learn. Behav., 22, 427-435) demonstrated that a
      California sea lion performed generalized identity matching-to-sample; that is,
      it chose visual stimulus A conditionally upon an identical sample A (AA
      matching), chose stimulus B conditionally upon sample B (BB matching) and chose
      stimulus C conditionally upon sample C (CC matching). The sea lion was later
      trained on 30 problems with similar stimuli to select comparison B conditionally
      upon sample A (AB matching), and trained on another 30 problems to select
      comparison C conditionally upon sample B (BC matching). Subsequently, the sea
      lion demonstrated trial-1 BA and CB matching and trial-1 AC and CA matching
      (Schusterman & Kastak 1993, Psychol. Rec., 43, 823-839). Matching of these
      derived relations defines the phenomenon of stimulus equivalence: when one member
      (A) of an equivalence class (ABC) becomes discriminative for a given behaviour,
      then B and C should become discriminative for the same behaviour. In the current
      study, we tested whether the sea lion could transfer the relations it had
      acquired between equivalence class members from a matching-to-sample paradigm to
      a simple discrimination paradigm. In 28 of 30 tests, the sea lion immediately
      transferred the discriminative function acquired by one member of an equivalence
      class to the remaining members of that class. Substitutability among members of
      an equivalence class is relevant to an analysis of referential communication, for
      example, the representational function of alarm calls. Copyright 1998 The
      Association for the Study of Animal Behaviour. Copyright 1998 The Association for
      the Study of Animal Behaviour.

PMID- 9632497
TI  - Natal attraction: allomaternal care and mother-infant separations in wild
      bottlenose dolphins.
AB  - To determine whether allomaternal care occurs among bottlenose dolphins, we
      examined patterns of association and mother-infant separations for eight infants
      (164.4 focal h) during the first 3 months of life. During the first week of life,
      three inexperienced females (nullipara and mothers of infants that did not
      survive the newborn period) attempted to take infants from their mothers 13
      times. Mothers responded by rapidly retrieving the infant and threatening the
      female. By the second week, mothers consistently allowed the same females to
      escort their infants to tens of metres away from them, suggesting that such
      separations were no longer risky, possibly because infants had imprinted on their
      mothers. To determine whether escorts benefited mothers after the first week, we
      compared maternal behaviour when infants were away from their mothers, but alone
      (solitary separations), to when infants were away, but with escorts (social
      separations). Mothers were less likely to forage and were more likely to engage
      in non-foraging activities (socialize, rest or travel) when infants were with
      young escorts (other dependent infants) compared with when infants were alone.
      When infants were with older (juvenile or adult) escorts, maternal activity did
      not differ significantly compared with when infants were alone. This result
      suggests that escorts did not benefit mothers by allowing them to forage.
      Inexperienced females that never raised an infant were more likely to escort
      newborns than were parous experienced females, supporting the 'learning to
      parent' hypothesis. Copyright 1998 The Association for the Study of Animal
      Behaviour. Copyright 1998 The Association for the Study of Animal Behaviour.

PMID- 9632498
TI  - How inclines affect the escape behaviour of a dune-dwelling lizard, Uma scoparia.
AB  - Although previous laboratory studies have commonly determined sprinting speeds of
      lizards on horizontal surfaces, the speeds and slopes used during the escapes of
      lizards in natural habitats with variable inclines are virtually unstudied. To
      quantify performance and the use of inclined surfaces during escape, we took
      advantage of the footprints left in soft substrate and the simple surface
      topography of the natural dune habitat of the Mojave fringe-toed lizard, U.
      scoparia. The lengths of 52 escape paths ranged from 1.7-34 m, and the inclines
      of 1-m portions of escape paths ranged from -25 degrees to 28 degrees, which
      effectively encompassed the entire range of inclines in the habitat. The
      cumulative frequencies (N=550) of inclines along 1-m intervals of the escape
      paths were not a simple random sample of the habitat. Less than 10% of the
      cumulative distance travelled during escape was bipedal, and the escape paths
      were relatively straight. Trajectories of the first metre of escapes were
      oriented significantly away from the presumed threat (observer) but were random
      with respect to the orientation of both the nearest cover and steepest incline.
      Eleven per cent of the cumulative number (N=1382) of strides measured were within
      90% of the maximum stride length within each path. Multiple regressions revealed
      that stride lengths (and hence speed) during escapes in the field were maximized
      on level surfaces with no turning. For lizards tested on a level racetrack in the
      laboratory, maximum speeds averaged 2.8 m/s (range=2.1-3.9) and approximated 75%
      of the maximum performance attained in the field.Copyright 1998 The Association
      for the Study of Animal Behaviour. Copyright 1998 The Association for the Study
      of Animal Behaviour.

PMID- 9632499
TI  - Cooperative breeding and monogamy in prairie voles: influence of the sire and
      geographical variation.
AB  - Mammalian monogamy is characterized by pair bonding and a relative absence of
      sexual dimorphism in body size. Alloparental behaviour is a characteristic of
      mammalian cooperative breeding systems. Studies of prairie voles, Microtus
      ochrogaster, from stock captured in a resource-abundant habitat in Illinois have
      supported the assumption that this species is a monogamous, cooperative breeder,
      while other studies of prairie voles from a more arid habitat in Kansas have
      called this assumption into question. We hypothesized that reported differences
      between these populations represented true intraspecific variation. Patterns of
      sexual dimorphism in body size, partner preferences and parental contact
      behaviour were compared in prairie voles from stocks originating in Illinois or
      Kansas. Both Illinois and Kansas voles showed a strong preference for a familiar
      partner, which is suggestive of monogamy. Sexual dimorphism in body size was
      observed in Kansas, but not Illinois voles. Illinois voles displayed
      significantly higher levels of parental contact behaviour than did voles from
      Kansas. When animals from Illinois and Kansas were crossed, the expression of
      parental contact behaviour of the 'hybrid' offspring followed the pattern seen in
      the population of origin of the sire. Removal of the sire prior to the birth of
      the litter increased alloparenting in Kansas voles, but removal of the sire was
      associated with lower levels of alloparenting in Illinois voles. Thus, some
      traits associated with the social system may show intraspecific variation and can
      be influenced by the presence or absence of the sire during rearing. Copyright
      1998 The Association for the Study of Animal Behaviour. Copyright 1998 The
      Association for the Study of Animal Behaviour.

PMID- 9632500
TI  - A test of how well the repeatability of courtship predicts its heritability.
AB  - We compared repeatability and heritability estimates for courtship traits in the
      housefly Musca domestica L., to test the expectation that the repeatability of a
      behaviour is an upper-bound estimate of its heritability. The repeatabilities
      across and within mating partners for two courtship traits, male wing buzzing
      (Buzz) and female wing extension (Wing-out), were compared to heritabilities
      calculated from the divergence among subpopulations due to founder-flush events
      or artificial selection. The male's Buzz showed highly significant
      repeatabilities within and across female partners, but the values ranged widely
      (0.3-0.5). The intensity of Buzz decreased significantly with successive
      courtship attempts to the same female, apparently as a male strategy to optimize
      his efforts to gain copulation by modulating behaviour for specific females.
      Repeatabilities for female Wing-out within and across male partners were not
      significant, but this trait yielded significant heritabilities in two assessments
      (based on successful courtships). We attribute this contradiction to biased
      sampling because only the subset of reluctant females met the necessary
      restriction to refuse copulation throughout four successive courtships. These
      results demonstrate that repeatabilities are labile within individuals and may
      actually underestimate heritabilities when there is a genetic predisposition not
      to repeat performance. We concur with related studies that repeatabilities can
      identify evolutionary potential, but we advise caution in interpreting low values
      or comparing their absolute values.Copyright 1998 The Association for the Study
      of Animal Behaviour. Copyright 1998 The Association for the Study of Animal
      Behaviour.

PMID- 9632501
TI  - Mate choice and mate competition influence male body size in Japanese medaka.
AB  - A sexual size dimorphism usually occurs when size-dependent reproductive
      advantages exist in only one sex. Studies on Japanese medaka, Oryzias latipes,
      have demonstrated reproductive size advantages in females but not in males, even
      though males and females are similar in body size. We conducted mate-choice and
      mate-copying tests in which a female could first associate with, then mate with,
      either a large (>/=1 sd+X standard length) or a small male (</=1 sd-X standard
      length). Large males obtained a mating advantage in both tests, and both mate
      choice and mate competition influenced their mating success. In the majority of
      trials, females associated with large males. Association preferences of females
      corresponded to their mating preferences when mate competition between males was
      weak; however, when mate competition was strong, large males obtained almost
      every mating regardless of female association preference. Preference for large
      males may provide females with a reproductive advantage if males mate multiply
      because small males become sperm-depleted sooner than large males. We found no
      indication that females copied the mating decisions of other females.
      Repeatability of female mating preference was low, not because females mated at
      random with respect to male size, but because most females consistently preferred
      large males. We also conducted mating tests at four density levels and found that
      large males maintained their mating advantage relative to small males at all
      densities. Thus, male and female medaka may be similar in body size because large
      size provides a fecundity advantage for females, as demonstrated in previous
      studies, and large size provides a mating advantage for males, as demonstrated in
      our study. Copyright 1998 The Association for the Study of Animal Behaviour.
      Copyright 1998 The Association for the Study of Animal Behaviour.

PMID- 9632502
TI  - Individual variation in male vocal traits and female mating preferences in Bufo
      americanus.
AB  - We investigated the amount of variation in mating behaviour between and within
      individual male and female American toads, because both sources of trait
      variation can influence the course of sexual selection. Males varied in all four
      call parameters investigated (dominant call frequency, pulse rate, call rate and
      call duration). Individual males lowered the dominant frequency of their call
      when they interacted vocally with nearby males. Dominant call frequency was more
      highly correlated with body size in vocally interacting males than in non
      interacting males. Pulse rate of calls primarily varied with water temperature.
      Call rate and call duration showed the most variation of the four call
      properties, but this variation was unrelated to male morphology or social
      interactions. Females varied in three aspects of mating behaviour: two measures
      of pair formation and their preference for dominant frequency of male calls. The
      body size of paired males varied between females both in pairings initiated by
      either sex and in pairings initiated only by females. Males chosen by females
      were usually larger than average, although age and prior breeding experience of
      females did not affect mate choice. Playback experiments indicated that female
      preference for calls of low dominant frequency depended on the temporal
      patterning of alternative calls presented. Each of the four male vocal properties
      showed significant repeatability, but only one of the three aspects of female
      mating behaviour was repeatable. We discuss how different degrees of
      repeatability in sexual traits of males and females may influence the action and
      detection of sexual selection in this and other species. Copyright 1998 The
      Association for the Study of Animal Behaviour. Copyright 1998 The Association for
      the Study of Animal Behaviour.

PMID- 9632503
TI  - What cues do brown-headed cowbirds use to locate red-winged blackbird host nests?
AB  - I examined ecological and behavioural variables influencing the susceptibility of
      red-winged blackbird, Agelaius phoeniceus, nests to brood parasitism by brown
      headed cowbirds, Molothrus ater, in a prairie-nesting population of redwings in
      southern Wisconsin. I compared the following variables between parasitized and
      unparasitized nests: proximity of nests to trees and other prominent perches;
      physical characteristics of nests such as nest height and cover; and aspects of
      host behaviour, including vocal behaviour and aggression directed towards female
      cowbirds. I used these data to discriminate among four non-exclusive hypotheses
      for how brood parasites locate host nests: the perch-proximity, nest-exposure,
      nesting-cue and host-activity hypotheses. Parasitized nests were significantly
      closer than unparasitized nests to trees in the 2 years of the study. There was
      no evidence that nest height or nest cover differed significantly between
      parasitized and unparasitized nests, suggesting that cowbirds do not use nest
      exposure as a cue for locating redwing nests. The responses of both parasitized
      and unparasitized redwings towards a female cowbird mount decreased with
      increasing mount presentation distance from the nest. There were no significant
      differences in responses towards the mount between parasitized and unparasitized
      redwings, giving no support for the nesting-cue hypothesis. Female redwings whose
      nests were subsequently parasitized gave significantly more nest-associated (type
      I) vocalizations during the egg-laying period than did unparasitized females.
      These findings suggest that female brown-headed cowbirds in search of potential
      host nests use trees to search from, and that female redwing vocalizations may
      serve as a proximate cue for cowbirds to locate redwing nests at appropriate
      stages for parasitism, giving support for both the perch-proximity and host
      activity hypotheses. Copyright 1998 The Association for the Study of Animal
      Behaviour. Copyright 1998 The Association for the Study of Animal Behaviour.

PMID- 9632504
TI  - Non-genetic benefits of mate choice: fecundity enhancement and sexy sons.
AB  - I compared reproductive success (lifetime number of fertilized eggs) as a
      function of mate choice among females of the stink bug, Nezara viridula L.
      (Hemiptera: Pentatomidae). 'Choosing' (C) females were placed with one of two
      males on alternate days. CI females chose between inexperienced males while CR
      females chose between males previously rejected by CI females. 'Non-choosing' (N)
      females were placed with the same male every day. Non-choosing NI, NR and NA
      females encountered, respectively, inexperienced males, previously rejected
      males, or previously accepted and mated males. Reproductive success was highest
      for CI females, showing direct selection on mate preferences. Reproductive
      success did not differ between CR and NR females, indicating that male quality,
      not the act of choosing a mate, affects fitness. CI females preferred males with
      longer antennae and their fecundity (lifetime number of eggs) was correlated with
      male antenna length, consistent with antenna length as an indicator of male
      ability to transfer nutritive sperm produced in paired harlequin lobes of the
      testes. Harlequin lobes were smaller in rejected than chosen males. In second
      generation mate choice trials, sons of NR females competed well against sons of
      NA females but not against sons of CI females. This suggests that non-genetic
      paternal contributions that decline with prior mating account for the
      attractiveness of sons because sons of CI and NA females shared the same fathers.
      Sons experiencing mating success came from larger eggs and egg size was greatest
      for CI females, perhaps as a consequence of paternal nutritional contributions.
      Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1998
      The Association for the Study of Animal Behaviour.

PMID- 9632505
TI  - Habitat-contingent reproductive behaviour in radio-implanted salamanders: a model
      and test.
AB  - All tiger salamanders, Ambystoma tigrinum, entering a small pond in New York
      state were given radio-implants and tracked throughout breeding to determine
      whether reproductive behaviour in nature differs from that described in
      laboratory studies. I formed an extended model of adult reproductive behaviour
      that included male and female strategies and differential use of habitat
      components in the breeding pond, and then tested four key predictions regarding
      adult movement using the sequence of positions of all salamanders between pond
      entry and exit. An unexpected, female-biased sex ratio during most courtship
      activity led to departures from the predicted behaviour, but in all other
      respects the behaviour of the males and females followed from the predictions.
      Apparent mate scanning in clear water, and weather assessment in pond-edge
      shallows just prior to emergence, are new indications for caudate amphibians.
      Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1998
      The Association for the Study of Animal Behaviour.

PMID- 9632506
TI  - Resource distribution, female home range dispersion and male spatial
      interactions: group structure in a solitary carnivore.
AB  - We monitored 74 (41 male, 33 female) radiocollared raccoons (Procyon lotor) from
      February 1990 to July 1992 on the Welder Wildlife Refuge, Texas, to relate male
      and female space use to each other and to the spatial distribution of water, a
      critical resource for raccoons. Female home ranges were spatially aggregated
      early in the study, when standing water occurred in only a few, widely separated
      patches on the study site, but were randomly distributed during seasons when
      water was more widely distributed. Adult females generally foraged and rested
      independently of other adults. Most adult males were arranged in spatial groups
      whose home ranges overlapped little with those of adjacent groups. These groups
      were usually composed of three to four individuals; Doncaster's (1990, J. theor.
      Biol., 143, 431-443) test for dynamic interaction and visual observations showed
      that group members tended to associate positively during resting and foraging
      activities in all seasons. Among raccoons, as among many other mammals, female
      spatial patterns are apparently determined primarily by resource distribution,
      whereas male patterns are influenced by the distribution of females. Copyright
      1998 The Association for the Study of Animal Behaviour. Copyright 1998 The
      Association for the Study of Animal Behaviour.

PMID- 9632507
TI  - Experimental evidence for spatial memory in foraging wild capuchin monkeys, Cebus
      apella.
AB  - Obtaining convincing evidence for spatial memory of natural food sources in wild
      animals is hard because the observer rarely knows as much about the available
      food as does the animal, and the ability of the animal to detect novel food
      sources is usually not measured. In this study, I took advantage of the scarcity
      of natural fruit sources in the subtropical winter to present a wild group of
      brown capuchin monkeys with a large-scale array of 15 feeding platforms spaced ca
      200 m apart. With this array, I could control the location, productivity and
      renewal schedule of the major fruit sources used by these animals. Combining an
      independent measurement of their detection field for these platforms with the
      known locations of the platforms, I calculated the expected patterns of movement
      among platform sites by the group under various models of 'random' foraging.
      These expected patterns were compared to the actual spatial movements of the
      group. The capuchin group moved significantly more often toward closer platforms
      and in straighter lines than expected by any random search model using their
      observed detection field of 82 m, although their behaviour did agree with such
      models for unrealistically large search fields of 225-350 m. I infer that the
      movements of this study group are likely to be guided by spatial memory. However,
      straight-line movement and a preference for closer platforms are in general not
      convincing evidence for spatial memory unless the detection field of the forager
      for the resources is known. Copyright 1998 The Association for the Study of
      Animal Behaviour. Copyright 1998 The Association for the Study of Animal
      Behaviour.

PMID- 9632508
TI  - Pathogen transmission as a selective force against cannibalism.
AB  - Cannibalism is uncommon in most species despite being taxonomically widespread.
      This rarity is surprising, because cannibalism can confer important nutritional
      and competitive advantages to the cannibal. A general, but untested, explanation
      for why cannibalism is rare is that cannibals may be especially likely to acquire
      pathogens from conspecifics, owing to greater genetic similarity among
      conspecifics and selection for host specificity and resistance to host immune
      defences among pathogens. We tested this hypothesis by contrasting the fitness
      consequences of intra- versus interspecific predation of diseased and non
      diseased prey. We fed cannibalistic tiger salamander (Ambystoma tigrinum) larvae
      diseased conspecifics, healthy conspecifics, diseased heterospecifics (a
      sympatric congener, small-mouthed salamanders, A. texanum), or healthy
      heterospecifics. Cannibals that ate diseased conspecifics were significantly less
      likely to survive to metamorphosis and grew significantly less than those that
      ate diseased heterospecifics, but none of the other groups differed. Tiger
      salamander larvae also preferentially preyed on heterospecifics when given a
      choice between healthy conspecifics and heterospecifics. These results suggest
      that pathogen transmission is an important cost of cannibalism and provide a
      general explanation for why cannibalism is infrequent in most species. Copyright
      1998 The Association for the Study of Animal Behaviour Copyright 1998 The
      Association for the Study of Animal Behaviour.

PMID- 9632509
TI  - Mate switching as a function of mate quality in convict cichlids, Cichlasoma
      nigrofasciatum.
AB  - We examined mate switching between mated pairs of monogamous convict cichlids as
      a function of mate quality (size). A mated pair was established in each half of a
      284-litre aquarium, an opaque partition separating the two pairs. When the
      partition was removed, mis-assorted pairs (large males with small females
      competing with small males with large females) re-sorted themselves such that the
      larger male and the larger female paired with each other 46% of the time. In
      contrast, when we exposed initially assorted pairs to each other, large pairs
      remained intact most of the time and dominated smaller pairs. The pair containing
      the large male, whether re-sorted or intact, dominated over the other pair and
      was the only one seen to spawn. Re-sortment resulted both from a preference of
      males for larger females and of females for larger males, and from the ability of
      larger individuals to displace their smaller consexual. Small females, however,
      when paired with a large male, often dominated large females and prevented the
      large female from mating with the large male. Re-sortment was also influenced by
      the compatibility of large individuals in their initial pairing situation. Large
      individuals that had been more compatible with their initial mates were less
      likely to switch mates. Our results support both the better-option and the
      incompatibility hypotheses of mate-switching. The availability of more than one
      breeding site in the aquarium had no effect on the frequency of re-sortment.
      Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1998
      The Association for the Study of Animal Behaviour.

PMID- 9632510
TI  - The effect of complete versus incomplete information on odour discrimination in a
      parasitic wasp.
AB  - We studied the function of learning in the parasitoid Leptopilina heterotoma by
      looking at discrimination of odour stimuli used in foraging for a host. To
      optimize the rate of encounters with hosts, these parasitoids are expected to
      assess the extent to which variation in host-substrate odours is reliably
      associated with variation in the presence of hosts, that is, substrate
      profitability. Where the association is reliable, parasitoids should attend to
      variation in odours and discriminate between them; where it is not, they should
      ignore it. We hypothesized that foraging decisions are based on the completeness
      of information the animal has about differences in substrate profitabilities. Our
      laboratory studies showed that discrimination and non-discrimination of odour
      stimuli are dynamic behavioural decisions that can be related to the degree of
      substrate variation and to an animal's informational state. In wind-tunnel
      studies, females learned to discriminate between odours from substrates that were
      qualitatively different, for example, between odours from apple and pear
      substrates or between yeast substrates with different C6 compounds added. They
      did not discriminate when differences were small (e.g. between odours from two
      apple varieties or between yeast patches with different concentrations of ethyl
      acetate), unless unrewarding experiences provided evidence of the absence of
      hosts in one of the substrates. Hence, we suggest that non-discrimination between
      odour stimuli in L. heterotoma is not a lack of ability to discriminate but a
      functional decision by the parasitoid. Copyright 1998 The Association for the
      Study of Animal Behaviour. Copyright 1998 The Association for the Study of Animal
      Behaviour.

PMID- 9632511
TI  - Predator discrimination error and the benefits of Mullerian mimicry.
AB  - Mullerian mimicry has traditionally been thought to benefit both unpalatable
      mimic and model species but recently its existence has been questioned. Even if
      both mimic and model species are unpalatable, they are unlikely to be equally
      unpalatable. It has been argued that the more unpalatable species will suffer a
      cost of increased predation because the presence of the more palatable mimic will
      increase its perceived palatability (by the predator), similar to that
      experienced by a model in Batesian mimicry. Yet, previous models of Mullerian
      mimicry have assumed that a predator can discriminate perfectly between available
      prey. We argue that this is not the case and that discrimination error is an
      important factor in determining the nature of mimetic relationships. Using
      computer simulations we show that the nature of a mimetic relationship will
      depend on the trade-off between the cost of an increase in perceived palatability
      and the benefits of a reduction in predator discrimination error. We show that
      mimicry can be unequivocally Mullerian, with both species benefiting, and propose
      that palatability should no longer be used as the sole defining characteristic of
      a mimetic relationship. Copyright 1998 The Association for the Study of Animal
      Behaviour. Copyright 1998 The Association for the Study of Animal Behaviour.

PMID- 9632512
TI  - Proteins in urine scent marks of male house mice extend the longevity of
      olfactory signals.
AB  - The binding of volatile semiochemicals to lipocalin proteins in many mammalian
      scent marks may provide a gradual release of volatile ligands, extending the life
      of airborne odour signals. We tested this by using menadione to displace
      semiochemical ligands from major urinary proteins (MUPs) in urine streaks
      obtained from adult male house mice, Mus domesticus, and assessed the responses
      of other males to these and to intact urine marks as they aged. Dominant male
      mice scent-mark their territories extensively with urine streaks; MUPs in these
      marks bind at least two semiochemically active molecules, 2-sec-butyl-4,5
      dihydrothiazole (thiazole) and 2,3-dehydro-exo-brevicomin (brevicomin),
      associated with the males' aggressive status. Wild-caught males (N=24), housed in
      individual enclosures, were presented with two glass slides, behind mesh to
      prevent contact, on which 10 ul of both unfamiliar urine and 0.5 mg/ml menadione
      in ethanol had been streaked. On one slide the urine and menadione solution were
      mixed to displace ligands; on the other they were separate (intact urine). We
      carried out tests 0, 0.5, 1 or 24 h after deposition, and matched them to changes
      in the concentration of thiazole and brevicomin within the intact and displaced
      marks. Males were hesitant to approach intact urine up to 1 h old but, when
      ligands were displaced, or were reduced to low levels by natural evaporation from
      intact urine streaks aged 24 h, their approach was similar to that to water and
      to menadione controls. Ligands did not appear to cause any longer term avoidance
      and, after the first approach, investigation increased with the freshness of
      urine regardless of when the ligands were displaced. This is the first direct
      demonstration that proteins evince a slow release of olfactory signals from
      mammalian scent marks. The nature of their response suggests that, from a
      distance, mice may be unable to tell whether airborne signals emanate from scent
      marks or from the donor himself and we suggest that this may provide territory
      owners with a major advantage in defending their territories.Copyright 1998 The
      Association for the Study of Animal Behaviour. Copyright 1998 The Association for
      the Study of Animal Behaviour.

PMID- 9632513
TI  - Functions of mudballing behaviour in the European fiddler crab Uca tangeri.
AB  - European fiddler crabs place mudballs around their burrow openings. Both males
      and females placed mudballs, but there were major differences between the sexes
      in mudballing behaviour, suggesting that the female's mudballs were a by-product
      of digging out the burrow whereas the male's may have additional functions. When
      the male's mudballs were removed experimentally, the number and intensity of male
      male agonistic interactions increased significantly. Experimentally visually
      isolated males spent longer making mudballs and less time waving. In a binary
      choice test, females were more likely to approach dummy males with mudballs,
      spent longer near these males and were more likely to enter their burrows than
      dummy males without mudballs. The same pattern was apparent for males with 30
      rather than 20 mudballs. These results are consistent with a dual function for
      mudballs in U. tangeri: to reduce the number and intensity of aggressive
      interactions between neighbouring males and to attract females. Copyright 1998
      The Association for the Study of Animal Behaviour. Copyright 1998 The Association
      for the Study of Animal Behaviour.

PMID- 9632514
TI  - Redstarts, Phoenicurus phoenicurus, can orient in a true-zero magnetic field.
AB  - I tested the migratory orientation of redstarts in a true-zero magnetic field to
      elucidate the importance to this species of access to either magnetic or
      celestial cues. I also tested the validity of the assumption on which all funnel
      experiments are based: that what we observe in an orientation funnel reflects
      what the bird would do if actually migrating. In a set of funnel experiments, I
      tested 47 night-migrating redstarts caught during their first autumn migration.
      Each bird was tested once under each of four experimental conditions in a semi
      randomized block-design. Upon completion of the final funnel tests the birds were
      fitted with light indicators and released. The results showed that redstarts can
      find the migratory direction on the basis of access to either celestial or
      magnetic cues. Thus, when celestial cues were available they could orient in a
      true-zero magnetic field. In addition, a starry sky facilitated high migratory
      activity as well as a clearly directed orientation. The release experiments
      showed that the vanishing bearings on nights with no wind were in good agreement
      with the direction of the funnel activity, but that the vanishing bearings were
      strongly influenced even by light wind. Copyright 1998 The Association for the
      Study of Animal Behaviour. Copyright 1998 The Association for the Study of Animal
      Behaviour.

PMID- 9632515
TI  - Position of operant costs affects visits to resources by laboratory mice, Mus
      musculus.
AB  - A recently recognized problem in consumer demand studies has been whether
      subjects should be allowed free exit from a resource cage that they have paid to
      enter. If decisions related to switches in behaviour are affected by the position
      of operant costs, then demand studies that offer free return routes from
      resources may result in different behavioural organization from those that split
      the same payment between entry to and exit from resources. We aimed to assess the
      extent of any such differences by comparing results from four operant treatments.
      The closed economy treatments differed in the position of the operant costs
      required to allow a mouse to enter a food cage and then return to the home cage.
      Three of the treatments carried the same overall cost: a full cost to enter the
      food cage; a full cost to leave the food cage; or with the cost split equally
      between entering and leaving the food cage. The fourth treatment imposed a half
      cost to enter the food cage but allowed free exit. The mice spent longer in
      whichever cage carried an exit cost. The most even distribution of their time was
      with the split cost. The number of visits undertaken depended on the magnitude of
      the cost, and on the resource cage for which the mice were paying. Significantly
      more visits were made when payment was required to enter the home cage. The mice
      responded to the immediate costs of entry to the cages, rather than the overall
      costs of a round trip. The lower number of visits made under higher costs was
      compensated for by the greater duration of those visits. Copyright 1998 The
      Association for the Study of Animal Behaviour. Copyright 1998 The Association for
      the Study of Animal Behaviour.

PMID- 9632516
TI  - Yellowhammers get fatter in the presence of a predator.
AB  - According to predictions from theoretical models, body mass and the daily
      foraging pattern of small birds in winter should be sensitive to predation risk.
      With increased risk of predation birds are expected to lower their body mass and
      shift their foraging to the afternoons. I studied the effect of predator presence
      on daily mass gain in captive yellowhammers, Emberiza citrinella. The birds were
      tested in unisex pairs, one bird being dominant over the other. In the first
      treatment the amount of food was restricted, and the daily pattern of mass gain
      was recorded. The second treatment was identical to the first, but, in addition,
      a stuffed sparrowhawk, Accipiter nisus, was displayed to the birds in the
      morning. Contrary to predictions from some theoretical models and other studies,
      the birds gained weight on days when the hawk was shown. Furthermore, the
      increased foraging happened mainly in the first half of the day, which also
      contradicts predictions from models. These results could be explained as a
      response to interrupted foraging, decreasing the probability of the birds
      acquiring the critical evening body mass. Alternatively, the birds increased
      their body reserves in preparation to leave a dangerous situation. Both dominance
      classes showed a similar response. The results suggest that the effects of
      predators on foraging interruptions should be included in models of daily
      routines of reserve accumulation. Copyright 1998 The Association for the Study of
      Animal Behaviour. Copyright 1998 The Association for the Study of Animal
      Behaviour.

PMID- 9632517
TI  - Territorial defence in speckled wood butterflies: do the hottest males always
      win?
AB  - Males of the butterfly Pararge aegeria defend sun spot territories on the forest
      floor as a strategy to locate females: the defence involves a spiral flight
      between two competing males. The success of any particular fight has been
      interpreted as following the simple rule 'resident wins, intruder loses' as
      predicted by game theory models. Here we use field experiments to show that
      temperature has a marked effect on the territorial defence of these ectothermic
      insects. The spiral flights were true contests, not conventional signals, so the
      flight endurance of the butterflies was an important factor in determining the
      result of the contest. Butterflies that were warmer could fly for longer and were
      more likely to win a contest; therefore temperature was an important component of
      contest asymmetry, and resident butterflies that increased their body
      temperatures by basking in sun spots were more likely to win than the intruding
      males which might have cooled down during flight around the site. The rule that
      the resident always wins is not disputed; however, the causal factors
      underpinning the rule are questioned. Copyright 1998 The Association for the
      Study of Animal Behaviour. Copyright 1998 The Association for the Study of Animal
      Behaviour.

PMID- 9632518
TI  - Individual variability in state-dependent feeding behaviour in three-spined
      sticklebacks.
AB  - We studied state-dependent feeding behaviour of three-spined sticklebacks,
      Gasterosteus aculeatus, during several trials of sequential encounters with 6-mm
      and 8-mm Asellus aquaticus prey. We used stomach fullness (the number of prey
      eaten previously) as an indicator for state, which we assumed to affect
      motivation for feeding. Dummy variable regression was used to study how the per
      trial energy consumption, the number of events experienced, feeding efficiency
      and the average time spent on each accepted prey depended on trial number, day
      and fish. A clear individual variability was found. Feeding behaviour was
      strongly related to the individual's recent feeding history (within a day). Logit
      regression models showed that the decision to accept or reject a prey encountered
      depended on the size of the fish as well as its state (stomach fullness).
      Although limited, our results demonstrate pronounced heterogeneity in feeding
      behaviour among individual fish. We discuss this phenomenon in the broader
      context of population regulatory mechanisms. Copyright 1998 The Association for
      the Study of Animal Behaviour. Copyright 1998 The Association for the Study of
      Animal Behaviour.

PMID- 9632519
TI  - Effects of temperature on anti-predator behaviour in the guppy, Poecilia
      reticulata.
AB  - Warmer environmental temperatures are likely to increase the frequency of
      predator-prey interactions in ectothermic animals, and therefore might be
      expected to influence anti-predator behaviour. In a first experiment, groups of
      recently fed guppies, placed in a novel environment, schooled significantly more
      closely at 26 degrees than at 22 degreesC. Changes in two of three measures of
      schooling tendency over time indicated that aggregation increased during the
      trial periods, probably as a result of increased familiarity within the
      experimental groups. In a second experiment, pairs of female guppies were tested
      at 22 degrees and 26 degreesC, with and without predation threat from a confined
      cichlid. From multifactor analysis of 18 behaviour types, temperature was shown
      to affect behavioural time budgets profoundly, particularly in the presence of
      the predator. At the higher temperature, a shift occurred from inactive anti
      predator behaviours and minimal foraging activity towards active predator
      inspection-related behaviours and a much higher level of feeding. Guppies in the
      warmer water might have been physically able to school more closely as a result
      of faster swimming ability, or might have used temperature as a cue indicating
      higher potential predation risk, and aggregated accordingly. The use of
      temperature as a source of information about the biotic environment is discussed.
      Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1998
      The Association for the Study of Animal Behaviour.

PMID- 9632520
TI  - Sedentary snakes and gullible geckos: predator-prey coevolution in nocturnal rock
      dwelling reptiles.
AB  - We investigated (1) the importance of chemical cues for predator detection by the
      nocturnal, rock-dwelling velvet gecko, Oedura lesueurii, and (2) how the lizards'
      responses to snake odour may have exerted selection on the foraging behaviours of
      a nocturnal elapid snake. This snake species (broadheaded snake, Hoplocephalus
      bungaroides) feeds primarily on velvet geckos, and does so by means of a
      distinctive foraging behaviour: the snakes remain sedentary in rock crevices for
      days or weeks, waiting to ambush geckos. Behavioural assays showed that geckos
      that are sympatric with this sedentary 'ambush' predator can detect and respond
      to the scent of the snake. Retreat-site selection experiments showed that geckos
      are less likely to enter crevices if the snake's scent is distributed over the
      entire rock surface, rather than localized to a central portion. Together, these
      data support the notion that the 'ambush' predator benefits by remaining
      sedentary within a retreat-site for long periods, because it thereby minimizes
      the extent to which it spreads its scent over the rocks forming the crevice.
      Geckos from a population sympatric with the 'ambush' predator responded strongly
      to the snake scent, but those from an allopatric population did not.
      Additionally, geckos from sympatric populations were able to detect the scent of
      a nocturnal snake that does not eat geckos (small-eyed snake, Rhinoplocephalus
      nigrescens), but did not modify their retreat-site selection or locomotory
      behaviours in response to this cue. Lizards from allopatric populations
      apparently did not detect the scent of small-eyed snakes. Collectively, our
      findings support an interpretation of predator-prey coevolution in the present
      system, and emphasize the importance of chemosensory cues to these rock-dwelling
      reptiles. Copyright 1998 The Association for the Study of Animal Behaviour.
      Copyright 1998 The Association for the Study of Animal Behaviour.

PMID- 9632521
TI  - Heat, safety or solitude? Using habitat selection experiments to identify a
      lizard's priorities.
AB  - Laboratory experiments with a rock-dwelling nocturnal gecko, Oedura lesueurii,
      showed that retreat-site selection (and other behaviours) are affected by the
      interplay between thermal benefits, social advantages and avoidance of predators.
      Velvet geckos were highly selective in habitat choice: they preferred artificial
      retreat-sites that mimic the thermal properties of natural rocks in full sun
      rather than those that mimic rocks in full shade; mature male geckos rarely
      shared retreat-sites with other adult males; and these lizards strongly avoided
      retreat-sites covered with the scent of a natural predator (the broadheaded
      snake, Hoplocephalus bungaroides). After documenting these preferences, we
      carried out additional trials in which two or more of these factors co-occurred,
      as is often the case in nature. Social dominance interacted with thermal benefits
      in determining retreat-site selection, with smaller (subordinate) males forced to
      use cooler retreat-sites when larger (dominant) males were present. Avoidance of
      predators was a higher priority than thermoregulation: the lizards would forego a
      warmer retreat-site with predator scent in favour of a cooler, unscented one.
      There was also an interplay between social dominance and predator scent: smaller
      males were forced to use either predator-scented retreat-sites or no retreat-site
      when larger males were present. General activity levels, and the frequencies of
      specific behavioural acts, also shifted in response to social and predator-scent
      cues. Our study emphasizes the complexity of habitat-selection behaviour in these
      lizards, and clarifies the criteria used in retreat-site selection when (as is
      commonly the case) the animal must choose between conflicting priorities.
      Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1998
      The Association for the Study of Animal Behaviour.

PMID- 9632524
TI  - IL-4 and IL-13 downregulate rolling adhesion of leukocytes to IL-1 or TNF-alpha
      activated endothelial cells by limiting the interval of E-selectin expression.
AB  - Leukocyte extravasation is governed by the endothelium, expressing a defined
      pattern of adhesion molecules in response to inflammatory stimuli. Among them, E
      selectin, which is expressed in response to interleukin 1 (IL-1) or tumour
      necrosis factor alpha (TNF-alpha), provides rolling adhesion of the circulating
      leukocytes, a transient and reversible interaction that initiates leukocyte
      extravasation. In our experiments, E-selectin expression culminated after 4 to 6
      h and declined thereafter. After 24 h a considerable amount of E-selectin was
      presented, reflecting its continuous expression in different inflammatory skin
      disorders. After preincubation of the endothelial cells with TNF-alpha together
      with IL-4 or IL-13, E-selectin mRNA transcription and protein expression were
      markedly reduced at 8 h and almost abolished at 20 h. In contrast, early E
      selectin expression between 2 to 6 h was not significantly impaired. In a
      rotating adherence assay that mimics physiological shear forces in circulation,
      preincubation of the endothelial cells with TNF-alpha for 4 and 20 h induced
      similar adherence of neutrophils, which was largely E-selectin dependent.
      According to the modified expression kinetics of E-selectin in the presence of IL
      4 of IL-13 rolling adhesion was unimpaired at 4 h but significantly diminished
      after 20 h of preincubation. Similar results were obtained with clones of the
      cutaneous T cell lymphoma cell line HUT78 highly expressing the E-selectin ligand
      cutaneous lymphocyte-associated Ag. Together, these data suggest that IL-4 and IL
      13 control the rolling adhesion by limiting the period of the induced E-selectin
      expression and may thereby confine the acute phase of leukocyte emigration.

PMID- 9632525
TI  - Exogenous interleukin 7 as a proliferative stimulant of early precursor B cells
      in mouse bone marrow: efficacy of IL-7 injection, IL-7 infusion and IL-7-anti-IL
      7 antibody complexes.
AB  - B lymphocyte development in mouse bone marrow (BM) occurs in association with
      stromal cells which provide essential growth factors, notably interleukin 7 (IL
      7). The ability of recombinant IL-7 given systemically by several modes of
      administration to stimulate proliferation of precursor B cells at successive
      stages of development was examined. Using immunofluorescence labelling and
      mitotic arrest, the in vivo proliferative cell dynamics of phenotypically defined
      B lineage cells was quantitated. Single injections of murine IL-7 (muIL-7) in low
      and intermediate doses stimulated production both of pro-B cells preceeding the
      expression of mu heavy chains and large pre-B cells expressing cytoplasmic mu. In
      contrast, higher doses were not stimulatory. Infusion of muIL-7 from subcutaneous
      micro-osmotic pumps produced a proliferative wave of TdT+ pro-B cells and pre-B
      cells followed by elevated numbers of postmitotic small pre-B cells and B cells.
      Stimulation tended to be followed by secondary oscillations of B lymphopoiesis or
      an IL-7 refractory state. Pronounced increases in TdT+ pro-B and pre-B cell
      production resulted from injecting small doses of either muIL-7 or human IL-7
      (hIL-7), complexed with anti-IL-7 antibody as carrier protein. The results
      indicate that exogenous IL-7 at optimal dose can markedly stimulate in vivo B
      lymphopoiesis from the earliest detectable TdT+ pro-B cell stage onward, and is
      effective when delivered as a cytokine-anticytokine complex.

PMID- 9632526
TI  - Interleukin 1 (IL-1) type I receptors mediate activation of rat hypothalamus
      pituitary-adrenal axis and interleukin 6 production as shown by receptor type
      selective deletion mutants of IL-1beta.
AB  - The cytokine interleukin 1 (IL-1) plays an important role in the activation of
      the hypothalamus-pituary-adrenal (HPA)-axis and interleukin 6 (IL-6) production
      during infection or inflammation. Which of the interleukin-1 receptor types
      mediates these effects is not known. To investigate this issue a pharmacological
      approach was chosen by using recently developed IL-1 receptor type selective
      ligands. Rats were given one of various doses of recombinant human IL-1beta (rhIL
      1beta; 1 and 10 microg/kg) and of several IL-1beta mutants (DeltaSND, DeltaQGE
      and DeltaI; 1, 10 and 100 microg/kg), that differ in their affinities for the IL
      1 type I receptor but have similar affinities for the IL-1 type II receptor. One
      hour after intravenous administration of rhIL-1beta or IL-1beta mutants, plasma
      levels of ACTH, corticosterone (cort) and IL-6 were measured. Doses of 1 and 10
      microg/kg rhIL-1beta markedly elevated plasma levels of ACTH, cort and IL-6.
      However, 10-100-fold higher doses of IL-1beta mutants DeltaSND and DeltaQGE and
      at least 100-fold higher doses of DeltaI have to be administered to increase
      plasma levels of ACTH, cort and IL-6. The potency differences correlate with
      their respective affinity for the type I receptor but not with that of the IL-1
      type II receptor. It is concluded that IL-1beta induced ACTH, cort and IL-6
      production is mediated by interleukin 1 type I receptors.

PMID- 9632527
TI  - Interferon gamma gene expression in rat central nervous system glial cells.
AB  - The expression of interferon gamma (TFN-gamma) mRNA in purified cultures of glial
      cells and leptomeningeal fibroblasts from the neonatal rat brain was analysed
      using semi-quantitative reverse transcriptase-polymerase chain reaction. IFN
      gamma specific transcripts were clearly detected in rat astrocytes and were
      upregulated after treatment with IFN-gamma itself or cycloheximide. In microglial
      cells, IFN-gamma transcripts were barely detectable in basal conditions and were
      upregulated by lipopolysaccharide and, to a lesser extent, by IFN-gamma or
      cycloheximide. IFN-gamma mRNA was neither detected not inducible in
      oligodendrocytes and leptomeningeal cells. The demonstration that IFN-gamma is
      expressed in astrocytes and microglia widens the putative role of these cells in
      local immunoregulation and antiviral responses.

PMID- 9632528
TI  - Sensitization of tnf-induced apoptosis with polyamine synthesis inhibitors in
      different human and murine tumour cell lines.
AB  - Rat/mouse T cell hybridoma-derived PC60 R55/R75 cells were used as a model to
      study tumour necrosis factor (TNF)-induced apoptosis. The role of ornithine
      decarboxylase (ODC) activity and polyamines in this process was investigated. In
      PC60 R55/R75 cells, TNF-induced ODC activity was completely suppressed by
      externally added spermine (Spm). TNF decreased the intracellular levels of the
      three polyamines Spm, spermidine (Spd) and putrescine (Put). A reduction of the
      intracellular [Spm] with methylglyoxal bis(quanyl hydrasone) (MGBG), CGP48644a,
      or bis(ethyl)norspermine (BENSpm), clearly sensitized the cells towards the
      apoptotic effect of TNF. Conversely, an increase in intracellular [Spm] with DFMO
      or externally added Spm reduced cellular sensitivity. Similar results were
      obtained after TNF treatment of the human cell lines Kym 39A6 (rhabdomyosarcoma),
      HeLaH21 (cervix carcinoma) and U937 (histocytoma) and after alphaFas treatment of
      HeLaH21, U937 and CEM-CM3 (human T cell line). These results suggest that a
      decrease of intracellular Spm levels rather then ODC activity per se is involved
      in the sensitization towards apoptosis induced by TNF or alphaFas.

PMID- 9632529
TI  - The growth response to tumour necrosis factor alpha of human gynaecological
      cancer cell lines.
AB  - The cytokine tumour necrosis factor alpha (TNF-alpha) is implicated in the
      regulation of diverse gynaecological cell types, its biological activity being
      potentially mediated by two distinct cell surface receptors (TNFR) of molecular
      weight 55 and 75 kDa, respectively. In this study the sensitivity to the growth
      regulatory properties of TNF-alpha of a panel of human cervical, endometrial and
      ovarian cancer cell lines was investigated in relation to the expression and
      biological activity of the 55- and 75-kDa receptor. There was no evidence of
      expression or function of the 75-kDa receptor in any of the cell lines tested.
      The expression and biological activity of the 55-kDa receptor was demonstrated in
      each TNF sensitive cell line, with one exception, the HOG-1 cervical cancer cell
      line. The data suggest that the 55-kDa receptor mediates the cellular response to
      TNF-alpha in sensitive gynaecological cancer cell lines but raises the
      possibility of the presence of a distinct receptor in HOG-1 cells.

PMID- 9632530
TI  - Clara cell protein: concentrations in cerebrospinal fluid, serum and amniotic
      fluid.
AB  - Clara cell protein (CC16) is an endogenous anti-inflammatory agent. It is
      produced mainly in the respiratory and urogenital tracts. CC16 has been
      quantified in serum, but not in cerebrospinal fluid (CSF). The aim of this study
      was to examine CSF CC16 in relation to age, gender and serum CC16, and to examine
      CC16 levels in parturients. If CC16 levels are increased with age and during
      pregnancy, it may be responsible for the attenuation of inflammatory diseases
      such as multiple sclerosis during these conditions. CC16 was measured in CSF and
      serum taken just before Caesarean section (n=33) or just before an elective
      surgical procedure in females (n=52) or males (n=31). Fetal serum, amniotic
      fluid, and maternal urine were also sampled during Caesarean section. CC16 levels
      in CSF did not differ between parturients and an age and gender matched non
      pregnant group, but was higher in male than in female patients. There was a
      significant and positive relationship between age and CSF CC16 levels and between
      serum and CSF CC16 levels. Fetal CC16 was significantly and positively correlated
      with amniotic fluid CC16. The present study suggests that CC16 found in CSF
      originates from passive diffusion from blood, and that CC16 found in amniotic
      fluid is derived from the fetal lung. During pregnancy, CC16 does not appear to
      contribute to alterations which occur in the progression of inflammatory
      disorders.

PMID- 9632531
TI  - Analysis of intragraft cytokine expression during early reperfusion after liver
      transplantation using semi-quantitative RT-PCR.
AB  - In the present study the intergraft mRNA formation immediately before and after
      transplantation of human livers was investigated by semi-quantitative polymerase
      chain reaction. The analysis was carried out with mRNA isolated from biopsies
      routinely taken perioperatively and included the determination of the expression
      of tumour necrosis factor alpha (TNF-alpha), interleukin (IL-6), IL-8, IL-10,
      transforming growth factor beta (TGF-beta) and beta-actin. It was found that
      biopsies obtained 30-60 min after reperfusion of the liver graft contained
      significantly higher levels of mRNA for TNF-alpha, IL-6 and IL-8 than biopsies
      collected subsequently to cold preservation. No such differences were obtained
      for TGF-beta and IL-10 mRNA. Considerable interindivdual differences were
      observed concerning the degree of inducibility, in particular for IL-6 mRNA.
      Retrospective comparison with the clinical course of the individual patients
      revealed a close and statistically significant correlation between low IL-6
      expression and the occurrence of acute rejection episodes within 30 postoperative
      days, while high IL-6 mRNA levels coincided with the absence of rejection signs.
      High values for TNF-alpha mRNA were associated with ensuing acute rejection
      episodes.

PMID- 9632534
TI  - Integrated microsatellite markers suitable for genetic studies of cytokine genes.
AB  - A panel of 13 highly informative dinucleotide repeats which are genetic markers
      for 17 cytokine genes and receptors is described. The marker panel is designed
      for use in fluorescence based semi-automated genotyping, with primers designed
      and labelled such that all 13 markers can be analysed in a single lane of a gel.
      Cytokine and cytokine receptors have a potential role in many diseases and
      pathological processes. Evidence suggests that cytokine production in vivo is
      influenced by polymorphisms within regulatory sequences of these genes. Genetic
      investigation of disease genes often requires genotyping of very large numbers of
      individuals. This panel of markers will, therefore, provide a useful tool to
      those wishing to undertake family-based linkage analysis studies of cytokine
      genes or large-scale association studies.

PMID- 9632533
TI  - IL-1beta and TNF-alpha, but not IFN-alpha, IFN-gamma, IL-6 or IL-8, are secretory
      mediators in human distal colon.
AB  - Inflammatory bowel disease (IBD) and HIV infection can cause diarrhoea which is
      accompanied by elevated cytokine levels. To elucidate a pathogenic role of
      cytokines, their effect on ion secretion was studied in human distal colon using
      the Ussing technique. Interluekin 1beta (IL-1beta) dose dependently increased
      short-circuit current (ISC). An ISC maximum of 2.5+/-0.3 micromol. h-1.cm-2 was
      reached at 20 ng/ml within 43+/-4 min. 22Na+ and 36Cl- fluxes were not altered
      and residual flux increased by 2.4+/-1.0 micromol.h-1.cm-2 indicating that the IL
      1beta-induced ISC is based on electrogenic bicarbonate secretion. IL-1beta had no
      effect on HT-29/B6 epithlial monolayers suggesting that IL-1beta does not act
      directly on the epithelium. Furthermore, in human colon the effect was not
      attenuated by removal of the submucosa (total stripping) pointing to a mediation
      step via subepithlial cells in the lamina propria. While tetrodotoxin and the 5
      lipoxygenase inhibitor ICI-230487 had no effect, indomethacin completely blocked
      IL-1beta action. Prostaglandin determination by RIA revealed an increased
      production of PGE2. At half maximum effective concentrations an additive action
      of tumour necrosis factor alpha (TNF-alpha) could be demonstrated on IL-1beta
      induced secretion. Interferon alpha (IFN-alpha), IFN-gamma, IL-6, and IL-8 had no
      seretory effect in human distal colon. None of the investigated cytokines altered
      the intestinal barrier function. By their secretory effects IL-1beta and TNF
      alpha, but not IFN-alpha, IFN-gamma, IL-6, and IL-8, may contribute to diarrhoea
      in IBD and AIDS.

PMID- 9632532
TI  - Interleukin 6, but not ciliary neurotrophic factor or leukaemia inhibitory
      factor, is responsible for the acute phase response to turpentine-induced
      myositis.
AB  - The acute phase response to inflammation is mediated in part by the endogenous
      production of pro-inflammatory cytokines. Interleukin 6 (IL-6) and members of its
      superfamily, including ciliary neurotrophic factor (CNTF) and leukaemia
      inhibitory factor (LIF) have been implicated as primary mediators of the hepatic
      acute phase response. In the present report, mice suffering a turpentine-induced
      myositis were passively immunized with antibodies against either IL-6, CNTF or
      LIF. Passive immunization against IL-6 attenuated the anorexia and completely
      prevented the hypoalbuminaemia, and increases in the serum concentration of the
      acute phase reactants, amyloid P, amyloid A and seromucoid. In contrast, passive
      immunization against either CNTF or LIF failed to modulate the anorexia, weight
      loss or hepatic acute phase protein responses. The findings suggest that IL-6,
      but not other members of its superfamily, is primarily responsible for the
      hepatic acute phase response, and contributes to the anorexia, associated with
      turpentine-induced myositis.

PMID- 9632535
TI  - Cytokines in juvenile rheumatoid arthritis (JRA).
AB  - Juvenile rheumatoid arthritis (JRA), unlike rheumatoid arthritis of adulthood
      (RA), is a heterogenous disease comprising at least five subtypes that differ in
      clinical course and prognosis, and require different therapeutical approaches. As
      compared to RA, the production of local and systemic cytokines in JRA have not
      yet been as extensively investigated. In this article we review the available
      literature on cytokine expression in serum and synovial fluid in all five
      different subtypes of JRA. Even though the data are still fragmentary, the
      evidence so far suggests that the determination of serum cytokines yields
      relevant information as to clinical subtype and inflammatory activity of the
      disease. Furthermore, the cytokine data suggest that the pathogenesis of JRA may
      even by more heterogenous than defined by the clinical subtypes. Finally, future
      directions of research in this area are proposed, and-based on the latest results
      arguments for (anti)cytokine therapies in JRA are critically discussed.

PMID- 9632536
TI  - Rotavirus-specific proteins are detected in murine macrophages in both intestinal
      and extraintestinal lymphoid tissues.
AB  - Rotaviruses replicate in mature, villous epithelial cells of the mammalian small
      intestine. Although rotavirus has not been detected in plasma of infants with
      rotavirus-induced gastroenteritis, rotavirus particles and rotavirus genomic RNA
      have been detected in extraintestinal sites (e.g. cerebrospinal fluid). Using a
      murine rotavirus strain well adapted to growth in the small intestines of
      suckling mice, we found that macrophages (and to a lesser extent B cells) in gut
      associated lymphoid tissue contained rotavirus-specific proteins, and that these
      antigen-containing cells travelled to sites distant to the intestine.

PMID- 9632537
TI  - Genetic inactivation of the extracellular cysteine protease enhances in vitro
      internalization of group A streptococci by human epithelial and endothelial
      cells.
AB  - Group A Streptococcus (GAS) produces an extracellular cysteine protease
      (streptococcal pyrogenic exotoxin B) that participates in virulence. We examined
      two pairs of isogenic GAS strains (serotype M2 and M3) for ability to be
      internalized by human umbilical vein endothelial cells and A549 human lung
      fibroblasts. For both host cell types, the level of internalization by the
      cysteine protease-negative mutant strains was significantly greater than the wild
      type parent organisms. The data suggest that expression of the cysteine protease
      contributes to extracellular survival, an observation consistent with recent
      results from mouse infection studies (Lukomski et al., Infect immun 1998; 66: 771
      6).

PMID- 9632538
TI  - Interaction of a group A Streptococcus within human plasma results in assembly of
      a surface plasminogen activator that contributes to occupancy of surface plasmin
      binding structures.
AB  - Group A streptococcal isolate 187061 incubated in human plasma or serum
      reconstituted with fibrinogen but not plasminogen-depleted plasma or serum alone
      acquired a surface plasminogen activator activity. Assembly of the surface
      plasminogen activator was inhibited by the presence of neutralizing antibodies to
      streptokinase. Once assembled, the bacterial-associated plasminogen activator
      could generate plasmin when incubated in human plasminogen, plasmin or serum
      which could bind to bacterial surface plasmin-binding structures despite the
      presence of host physiological inhibitors. These studies provide evidence that
      the pathways by which group A isolates interact with human plasmin(ogen) are
      potentially linked and may provide a mechanism for bacteria to acquire host
      enzymatic activity efficiently in the infected host.

PMID- 9632539
TI  - Apoptosis: a possible tactic of Haemophilus somnus for evasion of killing by
      bovine neutrophils?
AB  - Haemophilus somnus is an important veterinary pathogen that causes respiratory
      disease, arthritis, septicaemia and abortion in cattle and sheep. In the present
      study we investigated the possibility that H. somnus resists killing by bovine
      neutrophils, by causing the latter to undergo morphological changes consistent
      with apoptosis. Both serum-sensitive and serum-resistant strains of H. somnus
      enhanced bovine neutrophil chromatin condensation and shape change (i.e. zeiosis)
      in vitro, suggesting that the cells were undergoing apoptosis. Heat-killed or
      formalin-killed H. somnus had less effect than viable H. somnus. Chromatin
      margination of neutrophils was greater whenH. somnus was opsonized with adult
      bovine serum, which facilitates phagocytosis of the bacteria. H. somnus culture
      filtrates did not cause bovine neutrophil chromatin condensation. These findings
      suggest that direct contact with H. somnus is required for the maximal effect on
      bovine neutrophils. Apoptosis was confirmed by flow cytometry, using propidium
      iodide staining to detect DNA fragmentation. These findings suggest that H.
      somnus can evade killing by bovine neutrophils, in part, by inducing these cells
      to undergo apoptosis.

PMID- 9632540
TI  - Cloning and molecular analysis of genes encoding two immunodominant antigens of
      Ehrlichia risticii.
AB  - Ehrlichia risticii, the causative agent of Potomac horse fever, is an obligate
      intracellular rickettsial organism. To understand the role of 55 and 51
      kilodalton immunodominant antigens of E. risticii in strain variation, their
      genes from the 25-D and 90-12 strains were cloned, sequenced, and expressed in E.
      coli. Sequence analysis revealed that the gene for the 55 kDa antigen was present
      in a heat shock operon along with the gene for a ;10 kDa protein. Homology
      searches indicated that the 55 kDa antigen and the 10 kDa protein were homologues
      of E. coli GroEL and GroES proteins, respectively. There was no nucleotide
      sequence difference between the genes of the 55 kDa antigen, nor between the
      entire operons, from both strains of E. risticii. The sequence-based estimation
      of the sizes of the putative mature 51 kDa antigens of the 90-12 and 25-D strains
      were 52.7 kDa and 52.9 kDa, respectively. The 51 kDa antigens from the 90-12 and
      25-D strains shared a 98% identity in their deduced amino acid sequences. The
      difference in some of the amino acids may be responsible for variation in their
      mobilities on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, where
      the 51 kDa antigen of the 25-D strain migrates towards a ;2 kDa lower molecular
      weight region. In Western blots, a 155 kDa protein that appeared to be a trimer
      product of the 51 kDa antigen was identified. The 55 and 51 kDa antigens were
      overexpressed in E. coli using a commercial expression system, pRSET A,B,C
      (Invitrogen Inc., San Diego, CA, U.S. A.). The purified recombinant proteins
      cross-reacted with antisera to E. canis and E. sennetsu.

PMID- 9632542
TI  - Volume contents and index 

PMID- 9632541
TI  - Pathogenesis of Ross River virus-induced diseases: a role for viral quasispecies
      and persistence.

PMID- 9632543
TI  - Efficient Time Propagation Technique for MAS NMR Simulation: Application to
      Quadrupolar Nuclei.
AB  - The quantum mechanical Floquet theory is investigated in order to derive an
      efficient way of performing numerical calculations of the dynamics of nuclear
      spin systems in MAS NMR experiments. Here, we take advantage of time domain
      integration of the quantum evolution over one period as proposed by Eden et al.
      (1). But a full investigation of the propagator U(t, t0), and especially its
      dependence with respect to t and t0 within a formalized approach, leads to
      further simplifications and to a substantial reduction in computation time when
      performing powder averaging for any complex sequence. Such an approximation is
      suitable for quadrupolar nuclei (I > 1/2) and can be applied to the simulation of
      the RIACT (rotational induced adiabatic coherence transfer) phenomenon that
      occurs under special experimental conditions in spin locking experiments (2-4).
      The present method is also compared to the usual infinite dimensional Floquet
      space approach (5, 6), which is shown to be rather inefficient. As far as we
      know, it has never been reported for quadrupolar nuclei with I >/= 3/2 in spin
      locking experiments. The method can also be easily extended to other areas of
      spectroscopy. Copyright 1998 Academic Press.

PMID- 9632544
TI  - 13C-NOESY-HSQC with Split Carbon Evolution for Increased Resolution with
      Uniformly Labeled Proteins.
AB  - Two new pulse sequences are presented for the recording of 2D 13C-HSQC and 3D 13C
      NOESY-HSQC experiments, containing two consecutive carbon evolution periods. The
      two periods are separated by a z-filter which creates a clean CxHz-quantum state
      for evolution in the second period. Each period is incremented (in a non-constant
      time fashion) only to the extent that the defocusing of carbon inphase
      magnetization through J-coupling with neighboring carbons remains insignificant.
      Therefore, 13C homonuclear J-couplings are rendered ineffective, reducing the
      loss of signal and peak splitting commonly associated with long 13C evolution
      times. The two periods are incremented according to a special acquisition
      protocol employing a 13C-13C gradient echo to yield a data set analogous to one
      obtained by evolution over the added duration of both periods. The spectra
      recorded with the new technique on uniformly 13C-labeled proteins at twice the
      evolution time of the standard 13C-HSQC experiment display a nearly twofold
      enhancement of resolution in the carbon domain, while maintaining a good
      sensitivity even in the case of large proteins. Applied to the IIAMan protein of
      E. coli (31 kDa), the 13C-HSQC experiment recorded with a carbon evolution time
      of 2 x 8 ms showed a 36% decrease in linewidths compared to the standard 13C-HSQC
      experiment, and the S/N ratio of representative cross-peaks was reduced to 40%.
      This reduction reflects mostly the typical loss of intensity observed when
      recording with an increased resolution. The 13C-NOESY-HSQC experiment derived
      from the 13C-HSQC experiment yielded additional NOE restraints between resonances
      which previously had been unresolved. Copyright 1998 Academic Press.

PMID- 9632545
TI  - Fast Removal of Residual Water in Proton Spectra.
AB  - Quantification of metabolites in 1H spectra is difficult because of the presence
      of an unwanted water signal. Preprocessing, or removing the water contribution of
      a 1H spectrum, in the time domain is usually done using the state-space approach
      HSVD. HSVD removes the residual water and its side lobes, thereby reducing the
      baseline for the metabolites of interest and allowing subsequent data analysis
      using more sophisticated nonlinear least squares algorithms. However, the HSVD
      algorithm is computationally expensive because it estimates the signal subspace
      using the singular value decomposition (SVD). We show here that replacing the SVD
      by a low-rank revealing decomposition speeds up the computations without
      affecting the accuracy of the wanted parameter estimates. Copyright 1998 Academic
      Press.

PMID- 9632546
TI  - Selective NMR Experiments on Macromolecules: Implementation and Analysis of QUIET
      NOESY.
AB  - The QUIET-NOESY experiment (Zwahlen et al., J. Am. Chem Soc. 116, 362-368, 1994)
      is applied to measure the mobility of the flexible extensions in the large
      aggregate (800 kDa) of a small heat-shock protein. The proper choices of the
      experimental protocol and parameters are discussed in order to employ a
      simplified data analysis procedure. Further experimental verification of the
      proposed strategy is also presented using the cyclic peptide gramicidin S as a
      model compound. Under suitable conditions, the determinations based on the
      analysis of QUIET-NOESY data are affected to a negligible extent by the
      approximations that are introduced by the proposed approach. Copyright 1998
      Academic Press.

PMID- 9632547
TI  - 1D Determination of Long-Range Heteronuclear Coupling Constants by Gradient
      Enhanced SIMBA.
AB  - Two 1H-detected one-dimensional gradient enhanced experiments and corresponding
      reference experiments are proposed for the measurement of heteronuclear long
      range nJCH coupling constants in organic molecules. These experiments use inverse
      detection and selective carbon excitation, provide excellent suppression of
      protons not coupled to 13C, and are able to measure couplings from regions that
      are crowded in both the proton and carbon frequency ranges. The experiments are
      applied to determine the long-range nJCH couplings in the sucrose molecule,
      including coupling across the glycosidic linkage. These pulse sequences are shown
      to provide accurate and efficient measurements of coupling constants that would
      be difficult or time-consuming to measure by other techniques. Copyright 1998
      Academic Press.

PMID- 9632548
TI  - Computation of Orientational Averages in Solid-State NMR by Gaussian Spherical
      Quadrature.
AB  - We investigate Gaussian spherical quadrature as a method for calculating
      orientational averages in solid-state NMR. For the case of magic-angle-spinning
      sideband amplitudes of isolated spins-1/2, we demonstrate the superiority of
      Gaussian spherical quadrature over other orientational averaging methods.
      Depending on the shift anisotropy parameters and the desired accuracy, the
      computation speed is enhanced by a large factor (between two and many hundreds).
      In addition, a method for improving any present sampling scheme is devised. Such
      schemes are called SHREWD (Spherical Harmonic Reduction or Elimination by a
      Weighted Distribution). The role of orientational symmetry in solid-state NMR is
      explored. We also discuss the limitations of the Gaussian spherical quadrature
      methods. Copyright 1998 Academic Press.

PMID- 9632549
TI  - Proton Diffusion and T1 Relaxation in Polyacrylamide Gels: A Unified Approach
      Using Volume Averaging.
AB  - The structure of polyacrylamide gels was studied using proton spin-lattice
      relaxation and PFG diffusion methods. Polyacrylamide gels, with total polymer
      concentrations ranging from 0.25 to 0.35 g/ml and crosslinker concentrations from
      0 to 10% by weight, were studied. The data showed no effect of the crosslinker
      concentration on the diffusion of water molecules. The Ogston-Morris and Mackie
      Meares models fit the general trends observed for water diffusion in gels. The
      diffusion coefficients from the volume averaging method also fit the data, and
      this theory was able to account for the effects of water-gel interactions that
      are not accounted for in the other two theories. The averaging theory also did
      not require the physically unrealistic assumption, required in the other two
      theories, that the acrylamide fibers are of similar size to water molecules.
      Contrary to the diffusion data, T1 relaxation measurements showed a significant
      effect of crosslinker concentration on the relaxation of water in gels. The model
      developed using the Bloch equations and the volume averaging method described the
      effects of water adsorption on the gel medium on both the diffusion coefficients
      and the relaxation measurements. In the proposed model the gel medium was assumed
      to consist of three phases (i.e., bulk water, uncrosslinked acrylamide fibers,
      and a bisacrylamide crosslinker phase). The effects of the crosslinker
      concentration were accounted for by introducing the proton partition coefficient,
      Keq, between the bulk water and crosslinker phase. The derived relaxation
      equations were successful in fitting the experimental data. The partition
      coefficient, Keq, decreased significantly as the crosslinker concentration
      increased from 5 to 10% by weight. This trend is consistent with the idea that
      bisacrylamide tends to form hydrophobic regions with increasing crosslinker
      concentration. Copyright 1998 Academic Press.

PMID- 9632550
TI  - FT-EPR with a Nonresonant Probe: Use of a Truncated Coaxial Line.
AB  - A truncated transmission line probe (TLP) has been utilized to excite and detect
      time domain responses after pulsed excitation in electron paramagnetic resonance
      (EPR) spectroscopic experiments in the frequency range 200-400 MHz. The TLP
      device is a modified short-circuited coaxial line, which allows the irradiation
      of the sample by the traveling wave B1 fields in the frequency range of kilohertz
      to 30 GHz. In EPR studies at 300 MHz carrier frequency, with 10 W incident power,
      a 45 degrees pulse is 45 ns in duration. This corresponds to a 0.9-G B1 field.
      Using the TLP, time-domain responses from the solid N-methyl pyridinium tetra
      cyanoquinodimethane (TCNQ) were collected at 200, 250, 300, and 350 MHz, with the
      range limited by the amplifiers. In addition two tubes containing TCNQ placed
      side-by-side vertically along the axis of the probe were used to collect time
      domain responses in the presence of magnetic field gradients to test the
      feasibility of two-dimensional imaging using a TLP. The magnetic field gradient
      was steered in the xz plane and 36 projections were collected at 5 degrees
      intervals. Using filtered back-projection image reconstruction, the two
      dimensional spatial image in the xz plane was obtained at good resolution.
      Copyright 1998 Academic Press.

PMID- 9632551
TI  - A Generalized Estimate of the SLR B Polynomial Ripples for RF Pulse Generation.
AB  - The nonlinearity of the parameter relations for the Shinnar-Le Roux RF pulse
      design algorithm has induced to performa classification based on the features of
      the slice profile dueto the RF pulse. In the present paper a generalization ofthe
      relation between the ripple amplitudes of the SLR B polynomial and those of the
      slice profile is given. It allows generation of RF pulses with better slice
      profiles and slightly reduced energy, avoiding any a priori classification. The
      effect of our estimation has been shown by generating several pulses by
      generalized estimation of B polynomial ripples. In addition, their behavior has
      been compared to that of analogous pulses generated by means of the
      classification just mentioned. Copyright 1998 Academic Press.

PMID- 9632552
TI  - A Six-Pulse PASS MAS-NMR Technique Solved by a Phasor Method.
AB  - The PASS MAS-NMR technique is capable of recovering full intensities of the
      central resonances of a spectrum by phase adjusting the spinning sidebands. This
      variant of the original PASS sequence by Dixon uses six pi pulses instead of
      four. The addition of two pi pulses provides more flexibility in choosing the
      spacing between pulses and therefore eliminates pulse overlap and receiver dead
      time problems. The nonlinear, underdetermined PASS equations were solved using a
      graphical phasor method. All PASS sequences were successfully tested. A table of
      the six pulse delay times for different pitches is presented. Copyright 1998
      Academic Press.

PMID- 9632553
TI  - NMR Imaging Using Second Order Quadrupole Broadened Resonances.
AB  - Theoretical and experimental results for NMR imaging measurements of powdered
      materials using the +(1/2) to -(1/2) transition of (1/2)-integerspin nuclei in
      the presence of a very large second-order electric quadrupolar broadening are
      presented. An "effective spin-(1/2)" formalism is developed to account for
      additional effects due to the presence of quadrupolar interactions comparable in
      size to the Zeeman interaction. A large (7.9 mT/cm-A, with a maximum current of
      approximately 20 A), rapid ( approximately 30 us) pulsed linear gradient field is
      used with echoes and phase encoding techniques to obtain images in the limit
      gammaH1 is much narrower than the NMR linewidth. A one-dimensional projection of
      the second-order quadrupolar perturbed, 4-MHz-wide, +(1/2) left and right arrow 
      (1/2) transition for 63Cu in Cu2O powder is presented as an example. An
      experimental one-dimensional projection of a sample containing Cu2O and
      YBa2Cu3O6.7 is also presented. Copyright 1998 Academic Press.

PMID- 9632554
TI  - Contributions to the Gaussian line broadening of the proxyl spin probe EPR
      spectrum due to magnetic-field modulation and unresolved proton hyperfine
      structure.
AB  - A simple expression is derived to compute the total Gaussian linewidth of a Voigt
      line that is broadened by sinusoidal magnetic-field modulation as follows: delta
      HPPG(Hm)2 = delta HPPG(0)2 + kappa 2Hm2, where delta HPPG(Hm) is the Gaussian
      linewidth observed with an modulation amplitude Hm/2 and delta HPPG(0) is the
      Gaussian linewidth in the limit of zero modulation. The field modulation
      contributes an additional Gaussian broadening of kappa Hm, where kappa is a
      constant, which adds in quadrature to delta HPPG(0) to give the total Gaussian
      linewidth. Denoting the overall linewidth of the Voigt line in the absence of
      modulation broadening by delta HPP0(0), it is shown, both by analytical means and
      by spectral simulation, that the constant kappa is equal to 1/2 in the limit of
      Hm << = delta HPP0(0); however, using values of Hm as large as delta HPP0(0)
      leads to only minor departures from kappa = 1/2. The formulation is valid both
      for Lorentzian and Voigt lines and is tested for 2,2,5,5-tetramethylpyrrolidin-1
      oxyl-3-carboxylic acid (3-carboxy proxyl) in CCl4 and in aqueous buffer. This
      spin probe was studied because the proxyl group is the only major spin-probe
      moiety whose Gaussian linewidth had not been characterized in the literature. For
      3-carboxy proxyl, it is found that delta HPPG(0) = 1.04 +/- 0.01 G independent of
      solvent polarity. Precision values of the 14N hyperfine coupling constant for 3
      carboxy proxyl at 9.5 degrees C are as follows: 14.128 +/- 0.001 G in CCl4 and
      16.230 +/- 0.002 G in aqueous buffer. The temperature dependence of delta HPPG(0)
      and the 14N hyperfine coupling constant are reported as empirical equations.
      Results of the present work taken together with previously published data permits
      accurate correction for the effects of inhomogeneous broadening due to unresolved
      hyperfine structure and modulation broadening for the majority of spin probes in
      common use.

PMID- 9632555
TI  - A Pulsed Field Gradient NMR Technique for the Determination of the Structure of
      Suspensions of Non-Brownian Particles with Application to Packings of Spheres.
AB  - The internal structure of systems of particles in a liquid is studied with a
      novel NMR technique based on the measurement of the squared modulus of the
      magnetization in presence of a pulsed field gradient. The formalism is analogous
      to the one used in classical scattering techniques (light, X-rays, neutrons); it
      allows similar information to be obtained about the structure (in particular, the
      structure factor S(q)). The main improvement is that the range of particles sizes
      is 10 um to 1 mm, as compared with the range of the scattering techniques (<5
      um). The NMR technique was validated by studying packings of spherical particles
      of mean diameter 240 um created by sedimentation. The profile of the experimental
      squared modulus of the magnetization versus the wave vector provides results for
      the mean size of particles and the compacity. The main feature is that it depends
      on the pair distribution function, and the present results are in good agreement
      with a model based on the Percus-Yevick approximation. This technique is then
      particularly adapted to systems such as non-Brownian suspensions, fluidized beds,
      porous media, and sediments. Copyright 1998 Academic Press.

PMID- 9632556
TI  - Multivariate Image Analysis of Magnetic Resonance Images with the Direct
      Exponential Curve Resolution Algorithm (DECRA).
AB  - Antalek and Windig recently presented a fast method to resolve a series of NMR
      mixture spectra, where the contribution of the components varies with a decaying
      exponential [B. Antalek and W. Windig, J. Am. Chem. Soc. 118, 10,331-10,332
      (1996); W. Windig and B. Antalek, Chemom. Intell. Lab. Syst. 37, 241-254 (1997)].
      The method was called DECRA (direct exponential curve resolution algorithm). In
      this paper DECRA will be applied to two series of magnetic resonance images. The
      signal of one series is based upon T2 relaxation, and the other is based upon T1
      relaxation. In order to evaluate the technique, the magnetic resonance images of
      a phantom where used. A transformation is introduced to enable the application of
      DECRA to a T1 series of magnetic resonance images. A separate paper in this issue
      will describe the application of the techniques to magnetic resonance images of
      the human brain. Copyright 1998 Academic Press.

PMID- 9632557
TI  - Multivariate image analysis of magnetic resonance images with the direct
      exponential curve resolution algorithm (DECRA). Part 2: Application to human
      brain images.
AB  - Owing to the heterogeneity of living tissues, it is challenging to quantify
      tissue properties using magnetic resonance imaging. Within a single voxel,
      contributions to the signal may result from several types of 1H nuclei with
      varied chemical (e.g., -CH2-, -OH) and physical environments (e.g., tissue
      density, compartmentalization). Therefore, mixtures of 1H environments are
      prevalent. Furthermore, each unique type of 1H environment may possess a unique
      and characteristic spin-lattice relaxation time (T1) and spin-spin relaxation
      time (T2). A method for resolving these unique exponentials is introduced in a
      separate paper (Part 1. Algorithm and Model System) and uses the direct
      exponential curve resolution algorithm (DECRA). We present results from an
      analysis of images of the human head comprising brain tissues.

PMID- 9632558
TI  - Rapid-Pulsing Artifact-Free Double-Quantum-Filtered Homonuclear Spectroscopy.
AB  - Rapid pulsing artifacts are observed in the conventional phase-cycled carbon-13
      2D INADEQUATE experiment. By using the product operator formalism, it is shown
      that they result from the effects of imperfect 90 degrees and 180 degrees
      excitation pulses on the most abundant molecules containing only one isolated
      carbon-13 nucleus. The labeled longitudinal magnetization remaining at the end of
      one scan is recycled by the subsequent acquisition, giving rise to multiple
      quantum (p = 0, +/-1, +/-2, ellipsis) artifacts in the F1 dimension. By
      considering pairs of scans instead of single scans, a new phase cycle is
      proposed. It is based on a scheme for compensating for imperfections in the
      excitation cluster by a proper combination of the pulse phases in two consecutive
      scans. Because the artifacts are 90 degrees out of phase compared to the desired
      signal, a concomitant rearrangement of the receiver phase achieves suppression of
      all unwanted signals. Experiments are presented on menthol dissolved in CDCl3 as
      a test compound. Improvements in spectrum quality as well as increased
      sensitivity are discussed. Copyright 1998 Academic Press.

PMID- 9632559
TI  - Effect of Coupling between Rotational and Translational Brownian Motions on NMR
      Spin Relaxation: Consideration Using Green Function of Rigid Body Diffusion.
AB  - Using the Green function of arbitrary rigid Brownian diffusion (Goldstein,
      Biopolymers 33, 409-436, 1993), it was analytically shown that coupling between
      translation and rotation diffusion degrees of freedom does not affect the
      correlation functions relevant to the NMR intramolecular relaxation. It follows
      that spectral densities usually used for the anisotropic rotation diffusion
      (Woessner, J. Chem. Phys. 37, 647-654, 1962) can be regarded as exact in respect
      to the rotation-translation coupling for the spin system connected with a rigid
      body. Copyright 1998 Academic Press.

PMID- 9632560
TI  - Volume 128, Number 1 (1997), in Article No. MN971215 "A Novel Detection
      Estimation Scheme for Noisy NMR Signals: Applications to Delayed Acquisition
      Data," by Yung-Ya Lin, Paul Hodgkinson, Matthias Ernst, and Alexander Pines,
      pages 30-41:
AB  - Copyright

PMID- 9632562
TI  - Expression of Legionella pneumophila virulence traits in response to growth
      conditions.
AB  - In nature, Legionella pneumophila replicates exclusively as an intracellular
      parasite of amoebae, but it also persists in the environment as a free-living
      microbe. Studies of how this opportunistic pathogen recognizes and responds to
      distinct extracellular and intracellular environments identified a link between
      the growth phase and expression of traits previously correlated with virulence.
      When cultured in broth, only post-exponential-phase L. pneumophila was sodium
      sensitive, cytotoxic, osmotically resistant, competent to evade macrophage
      lysosomes, infectious, and motile. Likewise, the L. pneumophila phenotype changed
      during growth in macrophages. During the intracellular replication period, this
      bacterium was sodium resistant and lacked flagella; concomitant with macrophage
      lysis, L. pneumophila became sodium sensitive and flagellated. Expression of the
      virulent phenotype was a response to starvation, since exponential-phase L.
      pneumophila became cytotoxic, sodium sensitive, and motile after incubation in
      broth from stationary-phase cultures, except when it was supplemented with amino
      acids. Together, these data indicate that while nutrients are plentiful,
      intracellular L. pneumophila organisms are dedicated to replication; when amino
      acids become limiting, the progeny express virulence factors to escape the spent
      host, to disperse and survive in the aquatic environment, and to reestablish a
      protected intracellular niche favorable for growth.

PMID- 9632563
TI  - IS195, an insertion sequence-like element associated with protease genes in
      Porphyromonas gingivalis.
AB  - Porphyromonas gingivalis is recognized as an important etiologic agent in adult
      and early-onset periodontal disease. Proteases produced by this organism
      contribute to its virulence in mice. Protease-encoding genes have been shown to
      contain multiple copies of repeated nucleotide sequences. These conserved
      sequences have also been found in hemagglutinin genes. In the process of studying
      the genetic loci containing the conserved repeated sequences, we have
      characterized a prtP gene homolog from P. gingivalis W83 encoding a cysteine
      protease with Lys-X specificity. However, this prtP gene was interrupted by an
      insertion sequence-like element which we designated IS195. Furthermore, IS195 and
      another element, IS1126, were present downstream of prtP gene homologs (kgp)
      found in P. gingivalis H66 and 381. IS195, a 1,068-bp insertion sequence-like
      element, contained 11-bp inverted repeats at its termini and was bordered by 9-bp
      direct repeats presumed to be a transposition-mediated target site duplication.
      Its central region contained one large open reading frame encoding a predicted
      300-amino-acid protein which appeared to be a transposase. We isolated two
      naturally occurring variants of P. gingivalis W83, one carrying IS195 within the
      coding region of the prtP gene and another containing an intact prtP gene.
      Biochemical characterization revealed a lack of trypsin-like Lys-X specific
      proteolytic activity in the P. gingivalis W83 variant carrying the disrupted prtP
      gene. Studies using a mouse model revealed a reduction of virulence resulting
      from insertion of IS195 into the coding region of the prtP gene. An allelic
      exchange mutant defective in the prtP gene also was constructed and tested in
      vivo. It displayed intermediate virulence compared to that of the wild-type and
      prtP::IS195 mutant strains. We conclude that the Lys-X cysteine protease
      contributes to virulence in soft tissue infections.

PMID- 9632564
TI  - Heterogeneous expression and release of CD14 by human gingival fibroblasts:
      characterization and CD14-mediated interleukin-8 secretion in response to
      lipopolysaccharide.
AB  - To identify the role in periodontal inflammatory diseases of human gingival
      fibroblasts (HGF), the major constituents of gingival tissue, the expression of
      CD14, a possible lipopolysaccharide (LPS) receptor, and the release of soluble
      CD14 (sCD14) by HGF were examined. Among the HGF samples from the nine donors
      tested, more than 50% of the HGF from five donors expressed CD14 but less than
      20% of HGF from the other four donors did so, as determined by flow cytometric
      analysis. The CD14 expression on the cell surface was correlated with the
      expression of CD14 mRNA. The HGF and skin and lung fibroblasts tested expressed
      no CD18, which indicates that fibroblasts do not possess other LPS receptors,
      such as CD11b/CD18 and CD11c/CD18. The CD14 expression by the HGF was decreased
      after subculturing and was highest at the confluent stage of culture. The
      treatment of high-CD14-expressing (CD14(high)) HGF with phosphatidylinositol
      phospholipase C reduced CD14 expression; this result and the increase in a 55-kDa
      CD14 indicate that the membrane CD14 (mCD14) on the HGF may be a 55-kDa
      glycosylphosphatidylinositol-anchored protein. CD14(high) HGF spontaneously
      released 48- and 57-kDa sCD14. The total release of sCD14 by the HGF was
      augmented by gamma interferon and Escherichia coli LPS in accordance with the
      increased expression of mCD14. The CD14(high) HGF secreted interleukin-8 in
      response to LPS, and the secretion was completely inhibited by anti-CD14
      antibody. These results suggest that (i) HGF consist of populations that are
      heterogeneous on the basis of different levels of expression of CD14 and (ii)
      CD14(high) HGF secrete inflammatory cytokines in response to LPS via CD14.

PMID- 9632565
TI  - Inhibition of human peripheral blood mononuclear cell proliferation by
      Streptococcus pyogenes cell extract is associated with arginine deiminase
      activity.
AB  - Streptococcus pyogenes (group A Streptococcus) cell extracts (CE) have a
      remarkably powerful and dose-dependent inhibitory effect on antigen,
      superantigen, or mitogen-stimulated human peripheral blood mononuclear cell
      (PBMC) proliferation in vitro. Purification of the inhibitory component present
      in S. pyogenes type M5 (Manfredo strain) CE by anion-exchange chromatography
      followed by gel filtration chromatography showed that the inhibitor had an
      approximate native molecular mass of 100 kDa. Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis of purified inhibitory fractions followed by
      silver staining gave a single band with an approximate molecular mass of 47 kDa,
      indicating that the inhibitor is composed of two identical subunits. NH2-terminal
      sequencing of the protein revealed that it was identical to the previously
      characterized streptococcal acid glycoprotein (SAGP); this protein possesses
      between 31.5 and 39.0% amino acid identity with arginine deiminase (AD) from
      Mycoplasma hominis, Mycoplasma arginini, Pseudomonas putida, and Pseudomonas
      aeruginosa. AD enzyme activity was present in unfractionated CE prepared from a
      range of streptococcal strains, and partially purified inhibitory fractions of
      Manfredo CE also had high levels of activity. The inhibitory effect of Manfredo
      CE was overcome by the addition of L-arginine to proliferation assays in which
      human PBMC were stimulated with phytohemagglutinin. We conclude that SAGP, or its
      homolog, possesses AD activity and that the potent inhibition of proliferation of
      human T cells by streptococcal CE is due to activity of this enzyme.

PMID- 9632566
TI  - Comparison of Escherichia coli strains recovered from human cystitis and
      pyelonephritis infections in transurethrally challenged mice.
AB  - Urinary tract infection, most frequently caused by Escherichia coli, is one of
      the most common bacterial infections in humans. A vast amount of literature
      regarding the mechanisms through which E. coli induces pyelonephritis has
      accumulated. Although cystitis accounts for 95% of visits to physicians for
      symptoms of urinary tract infections, few in vivo studies have investigated
      possible differences between E. coli recovered from patients with clinical
      symptoms of cystitis and that from patients with symptoms of pyelonephritis.
      Epidemiological studies indicate that cystitis-associated strains appear to
      differ from pyelonephritis-associated strains in elaboration of some putative
      virulence factors. With transurethrally challenged mice we studied possible
      differences using three each of the most virulent pyelonephritis and cystitis E.
      coli strains in our collection. The results indicate that cystitis strains
      colonize the bladder more rapidly than do pyelonephritis strains, while the rates
      of kidney colonization are similar. Cystitis strains colonize the bladder in
      higher numbers, induce more pronounced histologic changes in the bladder, and are
      more rapidly eliminated from the mouse urinary tract than pyelonephritis strains.
      These results provide evidence that cystitis strains differ from pyelonephritis
      strains in this model, that this model is useful for the study of the
      uropathogenicity of cystitis strains, and that it would be unwise to use
      pyelonephritis strains to study putative virulence factors important in the
      development of cystitis.

PMID- 9632567
TI  - Effect of mild acid treatment on the survival, enteropathogenicity, and protein
      production in vibrio parahaemolyticus.
AB  - Vibrio parahaemolyticus is an important food-borne enteropathogen that encounters
      various adverse conditions in its native environment or during infection. Effects
      of mild acid treatment on survival under stress conditions, enteropathogenicity,
      and protein production in this pathogen were investigated. Logarithmically grown
      cells, at pH 7.5 shifted to pH 5.0 for 30 min, were more resistant to subsequent
      acid challenge at pH 4.4. A two-phase adaptive procedure (pH 5.8 for 30 min; pH
      5.0 for 30 min) was better than a single-phase procedure for enhancing the acid
      tolerance of this pathogen. The acid-adapted cells were cross-protected against
      the challenges of low salinity and thermal inactivation. One-dimensional
      polyacrylamide gel electrophoresis revealed that proteins with molecular masses
      of 6.4, 9.0, 13.6, 16.3, 18.9, 22.9, 24.4, 28.3, 33. 9, 36.9, 41.2, 47.6, 58.1,
      65.6, 80.5, 88.2, and 96.9 kDa were induced or significantly enhanced, while
      proteins of 25.3, 30.1, 30. 7, and 91.7 kDa were significantly inhibited. Two
      dimensional polyacrylamide gel electrophoresis revealed that 20 species of
      proteins were induced or significantly enhanced, while 26 species were inhibited.
      In assays conducted using the suckling mouse model, enteropathogenicity of the
      acid-adapted cells was significantly enhanced in terms of intestine/body weight
      ratio and in vivo recovery of infected cells.

PMID- 9632568
TI  - Pseudomonas aeruginosa exoenzyme S is a mitogen but not a superantigen for human
      T lymphocytes.
AB  - Virtually all cystic fibrosis (CF) patients become infected with Pseudomonas
      aeruginosa, and once the infection is established, the organism is rarely
      cleared. One of the P. aeruginosa virulence factors, exoenzyme S, has been shown
      to correlate with increased morbidity and mortality both in rat models of chronic
      pulmonary inflammation and in human CF patients. It has previously been shown
      that exoenzyme S is a potent stimulus for the proliferation of T cells in greater
      than 95% of adults, which could contribute to the pathogenesis of CF. The goal of
      this study was to determine the mechanism of T-cell stimulation by exoenzyme S in
      an effort to shed light on the immune response and contribute to understanding
      its role in P. aeruginosa pathogenesis. The current studies demonstrate that
      exoenzyme S stimulates naive T cells, since fetal blood lymphocytes proliferated
      and adult lymphocytes that expressed CD45RA proliferated. The percentage of T
      cells activated by exoenzyme S after a 4-h culture (as measured by CD69 surface
      expression) was intermediate in magnitude compared to levels induced by a panel
      of superantigens and mitogens. To determine the mechanism of activation, the
      requirement for accessory cells was investigated. The proliferative response to
      exoenzyme S was dependent on the presence of accessory cells but was not blocked
      by an anti-DR antibody. Exoenzyme S activated both CD4(+) and CD8(+) T cells, but
      CD4(+) T cells were preferentially activated. The Vbeta repertoire of donor T
      cells showed no preferential activation or preferential expansion after
      stimulation by exoenzyme S, suggesting that it is not a superantigen. Taken
      together, our data suggest that exoenzyme S is a T-cell mitogen but not a
      superantigen. Activation of a large percentage of T lymphocytes by exoenzyme S
      may produce a lymphocyte-mediated inflammatory response that should be considered
      in the pathogenesis of CF.

PMID- 9632569
TI  - Oral vaccination against tetanus: comparison of the immunogenicities of
      Salmonella strains expressing fragment C from the nirB and htrA promoters.
AB  - We have found the in vivo-regulated nirB promoter (PnirB) to be effective for
      directing expression of a number of antigens in salmonella in vivo. We wished to
      determine if other in vivo-regulated promoters have utility for antigen
      expression in salmonella and to compare the effectiveness of these promoters with
      that of PnirB. To this end, we have devised a scheme that allows the promoter
      element of the PnirB-fragment C plasmid pTETnir15 to be swapped with other
      promoters of interest. We demonstrate the usefulness of this system by replacing
      PnirB with PhtrA to create plasmid pTEThtrA1. htrA is a stress response gene that
      is required for virulence of salmonella in mice and survival within macrophages.
      Expression of fragment C in Salmonella typhimurium BRD509 (aroA aroD) harboring
      pTEThtrA1 (strain BRD937) correlated with growth temperature in vitro. A
      comparison was made of the immune responses to fragment C elicited in mice
      immunized orally with BRD937 or BRD847 (BRD509/pTETnir15) or subcutaneously with
      purified fragment C plus alhydrogel. High levels of anti-fragment C antibodies
      that persisted for at least 12 weeks were present in all groups of mice.
      Vaccination with BRD937 was the most effective means of immunization: the serum
      immunoglobulin G (IgG), IgA, and IgM anti-fragment C titers were higher in the
      BRD937-immunized mice throughout the duration of the study than in mice in the
      other groups. The kinetics of the serum anti-fragment C responses were different
      in different groups. The response was most rapid in the BRD937 group, with the
      titers almost at peak levels at 2 weeks postimmunization. Only the mice immunized
      with BRD937 or BRD847 developed an intestinal IgA response to fragment C. Again,
      the response was superior in the BRD937 group. The peak of the intestinal
      response was delayed with respect to the serum response. Analysis of the IgG
      subtype response to fragment C revealed a dominant IgG2a response in the
      salmonella-immunized mice, indicating a type 1 helper T-cell response to fragment
      C, whereas the major subtype in the group parenterally immunized with fragment C
      plus alhydrogel was IgG1. The IgG1/IgG2a ratio was much higher in sera of BRD937
      immunized mice than in sera of BRD847-immunized mice. At 15 to 20 weeks after
      immunization, the mice immunized with BRD937 or BRD847 were solidly immune to
      tetanus toxin and salmonella. The immune responses to fragment C seen in mice
      immunized with BRD937 are the strongest we have observed and indicate that the
      htrA promoter may be very useful for expressing foreign antigens in salmonella
      vaccine strains.

PMID- 9632571
TI  - Phase 1 evaluation of Vibrio cholerae O1, serotype Inaba, polysaccharide-cholera
      toxin conjugates in adult volunteers.
AB  - Conjugate vaccines were prepared by binding hydrazine-treated lipopolysaccharide
      (DeALPS) from Vibrio cholerae O1, serotype Inaba, to cholera toxin (CT) variants
      CT-1 and CT-2. Volunteers (n = 75) were injected with either 25 microg of DeALPS,
      alone or as a conjugate, or the licensed cellular vaccine containing 4 x 10(9)
      organisms each of serotypes Inaba and Ogawa per ml. No serious adverse reactions
      were observed. DeALPS alone did not elicit serum LPS or vibriocidal antibodies in
      mice and only low levels of immunoglobulin M (IgM) anti-LPS in the volunteers.
      Recipients of the cellular vaccine had the highest IgM anti-LPS levels, but the
      difference was not statistically significant from that elicited by the
      conjugates. The conjugates elicited the highest levels of IgG anti-LPS (DeALPS-CT
      2 > DeALPS-CT-1 > cellular vaccine). Both conjugates and the cellular vaccine
      elicited vibriocidal antibodies: after 8 months, recipients of cellular vaccine
      had the highest geometric mean titer (1,249), followed by DeALPS-CT-2 (588) and
      DeALPS-CT-1 (330). The correlation coefficient between IgG anti-LPS and 2
      mercaptoethanol (2-ME)-resistant vibriocidal antibodies was 0. 81 (P = 0.0004).
      Convalescent sera from cholera patients had a mean vibriocidal titer of 2,525
      that was removed by treatment with 2-ME. The vibriocidal activities of sera from
      all vaccine groups and from the patients were absorbed (>75%) by LPS but not by
      either CT-1 or CT-2. Conjugate-induced IgG vibriocidal antibodies persisted
      longer than those elicited by the whole-cell vaccine. Both conjugates, but not
      the cellular vaccine, elicited IgG anti-CT.

PMID- 9632570
TI  - Heterogeneity in levels of vacuolating cytotoxin gene (vacA) transcription among
      Helicobacter pylori strains.
AB  - Broth culture supernatants from Tox+ Helicobacter pylori strains induce
      vacuolation of HeLa cells in vitro and contain VacA in concentrations that are
      higher than those found in supernatants from Tox- H. pylori strains. To
      investigate the basis for this phenomenon, we analyzed the transcription of the
      vacuolating cytotoxin gene (vacA) in eight Tox+ strains (each with a type s1/m1
      vacA genotype) and nine Tox- strains (each with a type s2/m2 vacA genotype). Most
      of the Tox+ and Tox- strains tested used the same vacA transcriptional start
      point, but Tox+ strains yielded significantly stronger primer extension signal
      intensities than did Tox- strains (mean densitometry values of 15.8 +/- 1.9
      versus 8.9 +/- 1.7, P = 0. 0016). Correspondingly, when we introduced vacA::xylE
      transcriptional fusions into the chromosomes of a Tox+ strain (60190) and a Tox-
      strain (86-313), the level of XylE activity in 60190 vacA::xylE was about 30-fold
      higher than that in 86-313 vacA::xylE. Sequence analysis and promoter exchange
      experiments indicated that the different levels of vacA transcription in these
      two strains cannot be explained solely by a difference in promoter strength.
      These data indicate that Tox+ and Tox- H. pylori strains typically differ not
      only in the VacA amino acid sequence but also in the level of vacA transcription.

PMID- 9632572
TI  - Leishmania pifanoi amastigote antigen P-4: epitopes involved in T-cell
      responsiveness in human cutaneous leishmaniasis.
AB  - In experimental murine cutaneous leishmaniasis, the purified Leishmania pifanoi
      amastigote protein P-4 has been shown to induce significant protection against
      infection. Further, recent studies examining the response of peripheral blood
      mononuclear cells (PBMC) from Leishmania braziliensis-infected human patients
      have demonstrated that the P-4 protein selectively elicits a significant TH1-like
      response. Because a TH1-like response is associated with cure, epitope studies
      were conducted to further evaluate the human response to P-4. PBMC from confirmed
      cutaneous leishmaniasis patients infected with L. braziliensis in Rio de Janeiro,
      Brazil, an area where the disease is endemic, were examined for T-cell
      proliferation and/or cytokine production in response to whole-parasite
      homogenate, isolated P-4 protein, and/or P-4 peptides. Twenty of the 22 patients
      (91%) examined responded to the native P-4 protein by proliferation and/or gamma
      interferon (IFN-gamma) production. According to the proliferation data, PBMC from
      14 patients (64%) were found to respond to the intact P-4 protein (stimulation
      index of >/=2.5). Fifty-seven percent of the P-4-responsive patients studied
      responded to at least one of the P-4 peptides; 11 individual peptides were found
      to elicit a proliferative response. Of 17 patients examined for cytokine
      production, no PBMC produced detectable interleukin-4 in response to P-4 protein
      or peptides. However, PBMC from 14 patients (82%) produced significant levels of
      IFN-gamma (>/=20 pg/ml) in response to native P-4 protein. Nineteen of the 23
      peptides were found to elicit an IFN-gamma response from at least two patients.
      These data indicate that multiple epitopes spanning the entire P-4 molecule are
      responsible for the TH1-like immune response observed, indicating that the intact
      P-4 amastigote molecule, rather than selected peptides, may prove to be the most
      useful for leishmaniasis vaccine development.

PMID- 9632573
TI  - Cloning of the heat shock protein 70 (HSP70) gene of Ehrlichia sennetsu and
      differential expression of HSP70 and HSP60 mRNA after temperature upshift.
AB  - Ehrlichia sennetsu is the causative agent of human Sennetsu ehrlichiosis. Heat
      shock protein 60 (HSP60) and HSP70 (DnaK) are two major bacterial HSPs, and their
      interaction modulates the stress response. Previously, we cloned and sequenced
      groE and expressed groEL of E. sennetsu. HSP60 (GroEL) was immunogenic and cross
      reactive in Ehrlichia spp. The present study was designed to (i) characterize the
      HSP70 gene of this organism and (ii) determine whether the expression of these
      two HSPs is inducible upon exposure to heat stress. A gene encoding an HSP70
      homolog was isolated and sequenced from a gene library. The ehrlichial HSP70 gene
      encoded a 637-amino-acid protein, which had an approximate molecular mass of
      68,354 Da and which was homologous to DnaK of Escherichia coli. A DNA sequence
      resembling -35 and -10 promoter sequences of E. coli dnaK was observed upstream
      of the ehrlichial HSP70 gene. Alignment of the predicted amino acid sequence with
      that of E. coli DnaK and Brucella, Salmonella, Borrelia, Chlamydia, and
      Mycobacterium HSP70s showed 63, 67, 63, 62, 58, and 53% identity, respectively.
      By reverse transcription-PCR analysis, the mRNA levels of ehrlichial HSP70 and
      HSP60 were examined after temperature shifts from 28 to 37 degreesC and from 37
      to 40 degreesC. HSP70 mRNA induction levels were greater than those of HSP60 mRNA
      after a 37-to-40 degreesC temperature shift, whereas the reverse was true after a
      28-to-37 degreesC temperature shift. Our data suggest that HSP60 and HSP70 may
      play different roles during transfer from vector temperature to human body
      temperature and during a febrile condition characteristic of ehrlichial disease.
      This study also provides a useful model system for examining mRNA expression in
      obligatory intracellular bacteria.

PMID- 9632574
TI  - Phenotypic effect of isogenic uspA1 and uspA2 mutations on Moraxella catarrhalis
      035E.
AB  - The UspA surface antigen of Moraxella catarrhalis was recently shown to be
      comprised of two different proteins (UspA1 and UspA2) which share an internal
      region containing 140 amino acids with 93% identity (C. Aebi, I. Maciver, J. L.
      Latimer, L. D. Cope, M. K. Stevens, S. E. Thomas, G. H. McCracken, Jr., and E. J.
      Hansen, Infect. Immun. 65:4367-4377, 1997). Isogenic uspA1, uspA2, and uspA1
      uspA2 mutants were tested in a number of in vitro systems to determine what
      effect these mutations, either individually or together, might exert on the
      phenotype of M. catarrhalis 035E. Monoclonal antibodies specific for UspA1 or
      UspA2 were used in an indirect antibody accessibility assay to prove that both of
      these proteins were expressed on the surface of M. catarrhalis. All three mutants
      grew in vitro at the same rate and did not exhibit autoagglutination or
      hemagglutination properties that were detectably different from those of the wild
      type parent strain. When tested for the ability to adhere to human epithelial
      cells, the wild-type parent strain and the uspA2 mutant readily attached to Chang
      conjunctival cells. In contrast, the uspA1 mutant and the uspA1 uspA2 double
      mutant both attached to these epithelial cells at a level nearly 2 orders of
      magnitude lower than that obtained with the wild-type parent strain, a result
      which suggested that expression of UspA1 by M. catarrhalis is essential for
      attachment to these epithelial cells. Both the wild-type parent strain and the
      uspA1 mutant were resistant to the bactericidal activity of normal human serum,
      whereas the uspA2 mutant and the uspA1 uspA2 double mutant were readily killed by
      this serum. This latter result indicated that the presence of UspA2 is essential
      for expression of serum resistance by M. catarrhalis.

PMID- 9632575
TI  - Inhibition of murine splenic and mucosal lymphocyte function by enteric bacterial
      products.
AB  - Previously we showed that lysates of enteropathogenic Escherichia coli (EPEC)
      inhibit lymphokine production by mitogen-activated human peripheral blood and
      lamina propria mononuclear cells. The aims of the present study were to determine
      whether EPEC-inhibitory factors have similar effects on murine lymphoid
      populations in order to further delineate the mechanisms of alteration of
      cytokine production. Preexposure to EPEC lysates inhibited mitogen-stimulated
      interleukin-2 (IL-2), IL-4, and gamma interferon (IFN-gamma) production by murine
      spleen cells, but IL-10 production was increased. The inhibition was not due to
      increased apoptosis and was not blocked by neutralizating antibodies against IL
      10 or transforming growth factor beta (TGF-beta). EPEC lysates also inhibited
      mitogen-stimulated IL-2 and IFN-gamma production by CD11b-depleted spleen cells,
      IL-2 and IL-4 production by intraepithelial and Peyer's patch lymphocytes, IL-2
      production by the human T-cell line Jurkat, and antigen-stimulated IL-2
      production by murine spleen cells. Lysates obtained from Shiga-like toxin
      producing E. coli, E. coli RDEC-1, Citrobacter rodentium, and an EPEC espB
      insertion mutant all inhibited IL-2 and IL-4 production by mitogen-stimulated
      lymphoid cells. In conclusion, lysates of EPEC and related bacteria directly
      inhibit cytokine production by lymphoid cells from multiple sites by a mechanism
      that does not increase apoptosis or result from secondary effects of IL-10 or TGF
      beta.

PMID- 9632576
TI  - Purification of the inlB gene product of Listeria monocytogenes and demonstration
      of its biological activity.
AB  - Entry of Listeria monocytogenes into nonphagocytic cells requires the inlAB gene
      products. InlA and InlB are bacterial cell wall-associated polypeptides that can
      be released by sodium dodecyl sulfate treatment. By applying more gentle
      extraction methods, we have purified InlB in its native form. Treatment of
      bacteria with various nondenaturating agents including mutanolysin, thiol
      reagents, sodium chloride, and detergents like Triton X-100 or 3-[(3
      cholamidopropyl)-dimethylammonio]-1-propanesulfonate did not release substantial
      amounts of InlB from the bacterial cell wall. Instead, InlB was nearly
      quantitatively extracted in a solubilized form by treatment of bacteria with 1 M
      Tris-Cl or other protonated amines at pH 7.5. However, the reduced solubility of
      the extracted InlB in low-salt buffers hampered further biochemical purification.
      A panel of monoclonal antibodies against listerial Tris-Cl extracts containing
      InlB was therefore produced to generate reagents for use in affinity
      chromatography. One of the monoclonal antibodies enabled purification of the InlB
      protein to homogeneity with relatively high yields. When added externally,
      purified InlB associated with the surface of noninvasive bacteria such as
      Listeria innocua or an L. monocytogenes inlB2 mutant, where it promoted entry of
      these strains into Vero cells >300- and 17-fold, respectively. This effect was
      even more dramatic for HeLa cells, where the observed invasion was increased
      about 9,000- and 4,000-fold, respectively. The availability of purified native,
      invasion-competent InlB will allow analysis of the molecular basis of InlB
      mediated entry into tissue culture cell lines in greater detail.

PMID- 9632577
TI  - Cloning and characterization of an outer membrane protein of Vibrio vulnificus
      required for heme utilization: regulation of expression and determination of the
      gene sequence.
AB  - Vibrio vulnificus is a halophilic, marine pathogen that has been associated with
      septicemia and serious wound infections in patients with iron overload and
      preexisting liver disease. For V. vulnificus, the ability to acquire iron from
      the host has been shown to correlate with virulence. V. vulnificus is able to use
      host iron sources such as hemoglobin and heme. We previously constructed a fur
      mutant of V. vulnificus which constitutively expresses at least two iron
      regulated outer membrane proteins, of 72 and 77 kDa. The N-terminal amino acid
      sequence of the 77-kDa protein purified from the V. vulnificus fur mutant had 67%
      homology with the first 15 amino acids of the mature protein of the Vibrio
      cholerae heme receptor, HutA. In this report, we describe the cloning, DNA
      sequence, mutagenesis, and analysis of transcriptional regulation of the
      structural gene for HupA, the heme receptor of V. vulnificus. DNA sequencing of
      hupA demonstrated a single open reading frame of 712 amino acids that was 50%
      identical and 66% similar to the sequence of V. cholerae HutA and similar to
      those of other TonB-dependent outer membrane receptors. Primer extension analysis
      localized one promoter for the V. vulnificus hupA gene. Analysis of the promoter
      region of V. vulnificus hupA showed a sequence homologous to the consensus Fur
      box. Northern blot analysis showed that the transcript was strongly regulated by
      iron. An internal deletion in the V. vulnificus hupA gene, done by using marker
      exchange, resulted in the loss of expression of the 77-kDa protein and the loss
      of the ability to use hemin or hemoglobin as a source of iron. The hupA deletion
      mutant of V. vulnificus will be helpful in future studies of the role of heme
      iron in V. vulnificus pathogenesis.

PMID- 9632578
TI  - Chronic active hepatitis induced by Helicobacter hepaticus in the A/JCr mouse is
      associated with a Th1 cell-mediated immune response.
AB  - Helicobacter hepaticus infection in A/JCr mice results in chronic active
      hepatitis characterized by perivascular, periportal, and parenchymal infiltrates
      of mononuclear and polymorphonuclear cells. This study examined the development
      of hepatitis and the immune response of A/JCr mice to H. hepaticus infection. The
      humoral and cell-mediated T helper immune response was profiled by measuring the
      postinfection (p.i.) antibody response in serum, feces, and bile and by the
      production of cytokines and proliferative responses by splenic mononuclear cells
      to H. hepaticus antigens. Secretory immunoglobulin A (IgA) and systemic IgG2a
      antibody developed by 4 weeks p.i. and persisted through 12 months. Splenocytes
      from infected mice proliferated and produced more gamma interferon (IFN-gamma)
      than interleukin-4 (IL-4) or IL-5 when cultured with H. hepaticus outer membrane
      proteins. The predominantly IgG2a antibody response in serum and the in vitro
      production of IFN-gamma in excess of IL-4 or IL-5 are consistent with a Th1
      immune response reported in humans and mice infected with Helicobacter pylori and
      Helicobacter felis, respectively. Mice infected with H. hepaticus developed
      progressively severe perivascular, periportal, and hepatic parenchymal lesions
      consisting of lymphohistiocytic and plasmacytic cellular infiltrates. In
      addition, transmural typhlitis was observed at 12 months p.i. The
      characterization of a cell-mediated Th1 immune response to H. hepaticus infection
      in the A/JCr mouse should prove valuable as a model for experimental regimens
      which manipulate the host response to Helicobacter.

PMID- 9632579
TI  - In vitro effects of a high-molecular-weight heat-labile enterotoxin from
      enteroaggregative Escherichia coli.
AB  - The pathogenic mechanisms of enteroaggregative Escherichia coli (EAggEC)
      infection are not fully elucidated. In this work we show that an ammonium sulfate
      precipitate of culture supernatant of EAggEC strain 049766 increased the
      potential difference (PD) and the short-circuit current (Isc) in rat jejunal
      preparations mounted in Ussing chambers. The precipitate contained two major
      proteins of 108 and 116 kDa, which were partially copurified by chromatography in
      DEAE-cellulose. This chromatographic fraction (peak I) increased jejunal PD and
      Isc in a dose-dependent manner, accompanied by a decrease in tissue electrical
      resistance. These effects were inhibited by incubation of peak I at 75 degreesC
      for 15 min or for 1 h with proteinase K at 37 degreesC. Rabbit polyclonal
      antibodies against peak I containing both the 108- and 116-kDa proteins inhibited
      the enterotoxic effect. Specific polyclonal antibodies raised against the 108-kDa
      but not against the 116-kDa protein inhibited the enterotoxic effect, suggesting
      that the 108-kDa protein is the active toxic species. Moreover, another EAggEC
      strain (065126) producing the 116-kDa protein but not the 108-kDa protein had no
      effect on rat jejunal mucosa in the Ussing chamber. The >100-kDa fraction derived
      from prototype EAggEC strain 042, which also expressed both 108- and 116-kDa
      proteins, also produced an enterotoxic effect on rat jejunal preparations in
      Ussing chambers; however, the same strain cured of its 65-MDa adherence plasmid
      did not. A subclone derived from the 65-MDa plasmid expressing the 108-kDa toxin
      (and not the 116-kDa protein) elicited rises in Isc. Tissue exposed to any
      preparation containing the 108-kDa toxin exhibited similar histopathologic
      changes, characterized by increased mucus release, exfoliation of cells, and
      development of crypt abscesses. Our data suggest that some EAggEC strains produce
      a ca. 108-kDa enterotoxin/cytotoxin which is encoded on the large virulence
      plasmid.

PMID- 9632580
TI  - Pet, an autotransporter enterotoxin from enteroaggregative Escherichia coli.
AB  - Enteroaggregative Escherichia coli (EAEC) is an emerging cause of diarrheal
      illness. Clinical data suggest that diarrhea caused by EAEC is predominantly
      secretory in nature, but the responsible enterotoxin has not been described. Work
      from our laboratories has implicated a ca. 108-kDa protein as a heat-labile
      enterotoxin and cytotoxin, as evidenced by rises in short-circuit current and
      falls in tissue resistance in rat jejunal tissue mounted in an Ussing chamber.
      Here we report the genetic cloning, sequencing, and characterization of this high
      molecular-weight heat-labile toxin. The toxin (designated the plasmid-encoded
      toxin [Pet]) is encoded on the 65-MDa adherence-related plasmid of EAEC strain
      042. Nucleotide sequence analysis suggests that the toxin is a member of the
      autotransporter class of proteins, characterized by the presence of a conserved C
      terminal domain which forms a beta-barrel pore in the bacterial outer membrane
      and through which the mature protein is transported. The Pet toxin is highly
      homologous to the EspP protease of enterohemorrhagic E. coli and to EspC of
      enteropathogenic E. coli, an as yet cryptic protein. In addition to its potential
      role in EAEC infection, Pet represents the first enterotoxin within the
      autotransporter class of secreted proteins. We hypothesize that other closely
      related members of this class may also produce enterotoxic effects.

PMID- 9632581
TI  - Role of alveolar macrophages in initiation and regulation of inflammation in
      Pseudomonas aeruginosa pneumonia.
AB  - To evaluate the role of alveolar macrophages (AMs) in acute Pseudomonas
      aeruginosa pneumonia in mice, AMs were depleted by aerosol inhalation of
      liposomes containing clodronate disodium. AM-depleted mice were then
      intratracheally infected with 5 x 10(5) CFU of P. aeruginosa. In addition to
      monitoring neutrophil recruitment and chemokine releases, lung injury was
      evaluated soon after infection (8 h) and at a later time (48 h). At 8 h,
      depletion of AMs reduced neutrophil recruitment, chemokine release, and lung
      injury. At 48 h, however, depletion of AMs decreased bacterial clearance and
      resulted in delayed movement of neutrophils from the site of inflammation with
      aggravated lung injury. With instillation of 5 x 10(7) CFU of bacteria, AM
      depleted mice showed low mortality within 24 h of infection but high mortality at
      a later time, in contrast to non-AM-depleted mice. These results demonstrate that
      depletion of AMs has beneficial early effects but deleterious late effects on
      lung injury and survival in cases of P. aeruginosa pneumonia.

PMID- 9632582
TI  - Factors affecting the collagen binding capacity of Staphylococcus aureus.
AB  - To determine whether the ability of Staphylococcus aureus to bind collagen
      involves an adhesin other than the collagen adhesin encoded by cna, we examined
      the collagen binding capacity (CBC) of 32 strains of S. aureus. With only two
      exceptions, a high CBC corresponded with the presence of cna. Both exceptions
      involved cna-positive strains with a low CBC. The first was a single strain
      (ACH5) that encoded but did not express cna. The second were the mucoid strains
      Smith diffuse and M, both of which encoded and expressed cna but bound only
      minimal amounts of collagen. Analysis of capsule mutants suggests that the
      reduced CBC observed in the mucoid strains was due to masking of the collagen
      adhesin on the cell surface and that this masking effect is restricted to heavily
      encapsulated strains. Differences in the CBC of the remaining cna-positive
      strains were correlated to variations in the level of cna transcription and were
      independent of the number of B domain repeats in the cna gene. In all cna
      positive strains other than ACH5, cna transcription was temporally regulated,
      with cna mRNA levels being highest in cells taken from exponentially growing
      cultures and falling to almost undetectable levels as cultures entered the post
      exponential growth phase. The CBC was also highest with cells taken from
      exponentially growing cultures. Mutation of agr resulted in a slight increase in
      cna transcription and a corresponding increase in CBC during the exponential
      growth phase but did not affect the temporal pattern of cna transcription.
      Mutation of sar resulted in a more dramatic increase in CBC and a delay in the
      post-exponential-phase repression of cna transcription. Mutation of both sar and
      agr had an additive effect on both CBC and cna transcription. We conclude that
      (i) cna encodes the primary collagen-binding adhesin in S. aureus, (ii) sar is
      the primary regulatory element controlling expression of cna, and (iii) the
      regulatory effects of sar and agr on cna transcription are independent of the
      interaction between sar and agr.

PMID- 9632583
TI  - Immunization with Pneumocystis carinii gpA is immunogenic but not protective in a
      mouse model of P. carinii pneumonia.
AB  - Immunization with whole Pneumocystis carinii has been shown to protect mice from
      the development of P. carinii pneumonia (PCP) when they are subsequently
      immunosuppressed and challenged with viable organisms. To determine whether these
      results could be duplicated by using a subunit vaccine, we examined the
      immunogenicity and efficacy of an immunization strategy based on P. carinii gpA.
      This antigen was chosen for study because passive immunoprophylaxis, based on
      gpA, has been shown to be partially protective in various animal models of
      infection. Immunization with gpA produced an anti-gpA specific antibody response
      comparable to that resulting from immunization with whole organisms. However, in
      contrast to immunization with whole P. carinii, which was protective,
      immunization with gpA did not protect T-cell-depleted mice from the development
      of PCP. These studies suggest that other antigens in addition to gpA need to be
      evaluated for their role in protective immunity against P. carinii.

PMID- 9632584
TI  - Mucosal delivery of murine interleukin-2 (IL-2) and IL-6 by recombinant strains
      of Lactococcus lactis coexpressing antigen and cytokine.
AB  - Lactococcus lactis is a nonpathogenic and noncolonizing bacterium which is being
      developed as a vaccine delivery vehicle for immunization by mucosal routes. To
      determine whether lactococci can also deliver cytokines to the immune system, we
      have constructed novel constitutive expression strains of L. lactis which
      accumulate a test antigen, tetanus toxin fragment C (TTFC), within the
      cytoplasmic compartment and also secrete either murine interleukin-2 (IL-2) or IL
      6. When mice were immunized intranasally with various different expression
      strains of L. lactis, the anti-TTFC antibody titers increased more rapidly and
      were substantially higher in mice immunized with the bacterial strains which
      secreted IL-2 or IL-6 in addition to their production of TTFC. This adjuvant
      effect was lost when the recombinant strains of L. lactis were killed by
      pretreatment with mitomycin C and could therefore be attributed to the secretion
      of IL-2 or IL-6 by the recombinant lactococci. These results provide the first
      example of the use of a cytokine-secreting, noninvasive experimental bacterial
      vaccine vector to enhance immune responses to a coexpressed heterologous antigen
      and point the way to experiments which will test the possible therapeutic
      efficacy of this mode of cytokine delivery.

PMID- 9632585
TI  - Identification of new cytotoxic T-cell epitopes on the 38-kilodalton
      lipoglycoprotein of Mycobacterium tuberculosis by using lipopeptides.
AB  - Induction of cytotoxic T lymphocytes (CTLs) by vaccination has been shown to
      protect against bacterial, viral, and tumoral challenge. The aim of this study
      was to identify CTL epitopes on the 38-kDa lipoglycoprotein from Mycobacterium
      tuberculosis. The identification of these CTL epitopes was based on synthesizing
      peptides designed from the 38-kDa lipoglycoprotein, with known major
      histocompatibility complex class I (MHC-I) binding motifs (H-2Db), and studying
      their ability to up-regulate and stabilize MHC-I molecules on the mouse lymphoma
      cell line RMA-S. To improve the capacity of the identified peptides to induce CTL
      responses in mice, palmitic acid with a cysteine-serine-serine spacer amino acid
      sequence was attached to the amino terminus of the peptide. Two of five peptides
      with H-2Db binding motifs and their corresponding lipopeptides up-regulated and
      stabilized the H-2Db molecules on RMA-S cells. Both lipopeptides, in combination
      with incomplete Freund's adjuvant, induced CTL responses in C57BL/6 (H-2(b))
      mice. Moreover, the lipopeptide induced stronger CTL responses than the peptide.
      The capacity of the various lipopeptides to induce CTL displayed a good
      relationship with the ability of the (lipo)peptide to up-regulate and to
      stabilize H-2Db molecules. The capacity of the peptides and lipopeptides to up
      regulate and stabilize MHC-I expression can therefore be used to predict their
      potential to function as a CTL epitope. The newly identified CTL epitopes and
      their lipid derivatives provide us with important information for future M.
      tuberculosis vaccine design.

PMID- 9632586
TI  - Bioluminescence as a reporter of intracellular survival of Bordetella
      bronchiseptica in murine phagocytes.
AB  - The uptake and persistence of Bordetella bronchiseptica was characterized in
      murine phagocytes by using a novel bioluminescence-based reporter system. A mini
      Tn5 promoter probe carrying the intact lux operon from the terrestrial bacterium
      Photorhabdus luminescens which allowed measurement of light output without the
      addition of exogenous substrate was constructed. It was used to create a pool of
      bioluminescent fusion strains of B. bronchiseptica. The internalization and
      persistence in murine macrophages of a constitutive bioluminescent strain of B.
      bronchiseptica was monitored by luminometry and by fluorescence and electron
      microscopy. The number of bacteria internalized, in a microfilament-dependent
      process, by a mouse macrophage-like cell line after 2 h was approximately 1% of
      the inoculum for several different multiplicities of infection (MOI). At an MOI
      of <500:1 (bacteria to macrophages), viable numbers of intracellular bacteria
      declined over a 4-day period. However, at an MOI of >/=500:1, long-term survival
      was enhanced, with viable bacteria recovered up to 4 days postinfection with
      little decline in numbers, indicating that a critical population size may have
      been essential for intracellular persistence. No evidence of macrophage killing
      by intracellular bacteria was detected over the 4-day period. Intracellular
      bioluminescent B. bronchiseptica organisms in mouse peritoneal cells were
      detected at 24 and 48 h after intraperitoneal injection of mice. Bioluminescence
      is shown to act as a convenient real-time technique for monitoring of
      intracellular survival of B. bronchiseptica in vitro and may provide a suitable
      means for examining the role of long-term intracellular survival of the bacterium
      in the host.

PMID- 9632587
TI  - The Salmonella typhimurium AhpC polypeptide is not essential for virulence in
      BALB/c mice but is recognized as an antigen during infection.
AB  - The OxyR regulon is known to mediate protection against oxidizing agents in
      Salmonella typhimurium. We reported previously that ahp, one of the OxyR
      regulated loci, is induced during macrophage interaction (K. P. Francis, P. D.
      Taylor, C. J. Inchley, and M. P. Gallagher, J. Bacteriol. 179:4046-4048, 1997).
      We now report on the effects of disrupting ahp or oxyR on virulence in a BALB/c
      mouse model. Surprisingly, insertion of a Mudlux derivative within ahpC was found
      to result in attenuation, while irreversible inactivation of the locus through
      insertion of a cml cassette did not. An SL1344 derivative carrying an oxyR::kan
      disruption was also found to be as virulent as the parental strain. Moreover,
      both cell-mediated and humoral responses to AhpC were found to develop during the
      course of infection, probably through T-helper-cell (type I) activation. These
      results indicate that, although not essential for virulence, AhpC is expressed by
      S. typhimurium during infection of BALB/c mice and constitutes a target for the
      immune system.

PMID- 9632588
TI  - Immunological and molecular characterization of three variant subtype P1.14
      strains of Neisseria meningitidis.
AB  - Epidemic outbreaks of group B meningococcal disease exhibit a clonal nature
      consisting of a common serotype-subtype. Subtype-specific monoclonal antibodies
      (MAbs) directed toward two variable regions (VR1 and VR2) of the class 1 protein
      of Neisseria meningitidis are used in this classification scheme. A new MAb was
      developed to classify a nonsubtypeable (NST) strain of N. meningitidis, 7967.
      This MAb bound to both the NST strain and the prototype subtype P1. 14 strain,
      S3446, by dot blot analysis. However, a MAb produced to the prototype P1.14
      strain did not bind to strain 7967. Sixteen additional strains were further
      identified as P1.14 with the prototype MAb; of these, 15 strains bound both MAbs.
      Differences in the characteristics of binding of both antibodies to the three
      apparently diverse P1.14 strains were studied further by using outer membrane
      complex proteins, immobilized peptides, and soluble peptides. Deduced amino acid
      analysis suggested that both MAbs bind to VR2 and that single amino acid changes
      within VR2 (KM, NM, or KK) might explain the differences in binding
      characteristics. These results demonstrated that minor variations which exist
      within subtype variable regions may be clearly identified only by a combination
      of molecular and immunologic testing. The impact of subtype variation will become
      more evident as subtype-specific vaccines are developed and tested for efficacy.

PMID- 9632589
TI  - Immune responses against major outer membrane antigens of Neisseria meningitidis
      in vaccinees and controls who contracted meningococcal disease during the
      Norwegian serogroup B protection trial.
AB  - Sera from vaccinees and controls who contracted serogroup B meningococcal disease
      during the blinded and open parts of a two-dose protection trial in Norway were
      compared for antigen-specific and bactericidal antibodies against vaccine strain
      44/76 (B:15:P1.7,16). From 16 of 20 (80%) vaccinees and 26 of 35 (74%) controls,
      one or more serum samples (n = 104) were collected during the acute phase (1 to 4
      days), early convalescent phase (5 to 79 days), and late convalescent phase (8 to
      31 months) after onset of disease. Binding of immunoglobulin G (IgG) to the major
      outer membrane antigens (80- and 70-kDa proteins, class 1, 3, and 5 proteins, and
      lipopolysaccharide [LPS]) on immunoblots was measured by digital image analysis.
      Specific IgG levels in vaccinees increased from acute to early convalescent
      phases, followed by a decline, while controls showed a small increase over time.
      Vaccinees had significantly higher levels than controls against class 1 and 3
      porins and LPS in acute sera, against all antigens during early convalescence,
      and against class 1 and 3 porins in the later sera. Vaccinees who were infected
      with strains expressing subtype P1.7,16 proteins demonstrated a level of IgG
      binding to protein P1.7,16 with early-convalescent-phase sera that was fourfold
      higher than that of those infected with other strains. Bactericidal titers in
      serum against the vaccine strain were 192-fold higher for vaccinees than those
      for controls during early convalescence, but similarly low levels were found
      during late convalescence. A vaccine-induced anamnestic response of specific and
      functional antibody activities was thus shown, but the decrease in protection
      over time after vaccination indicated that two vaccine doses did not induce
      sufficient levels of long-term protective antibodies.

PMID- 9632590
TI  - Induction of protective immune responses by immunization with linear multiepitope
      peptides based on conserved sequences from Plasmodium falciparum antigens.
AB  - A cysteine-containing peptide motif, EWSPCSVTCG, is found highly conserved in the
      circumsporozoite protein (CSP) and the thrombospondin-related anonymous protein
      (TRAP) of all the Plasmodium species analyzed so far and has been shown to be
      crucially involved in the sporozoite invasion of hepatocytes. We have recently
      shown that peptide sequences containing this motif, and also the antibodies
      raised against the motif, inhibit the merozoite invasion of erythrocytes.
      However, during natural infection, and upon immunization with recombinant CSP,
      this motif represents a cryptic epitope. Here we present the results of
      immunization studies with two linear multiepitopic constructs, a 60-residue (P60)
      and a 32-residue (P32) peptide, containing the conserved motif sequence. Both the
      peptides per se generated high levels of specific antibodies in BALB/c mice. P32
      was found to be genetically restricted to H-2(d) and H-2(b) haplotypes of mice,
      whereas P60 was found to be immunogenic in five different strains of mice. The
      antibody response was predominantly targeted to the otherwise cryptic, conserved
      motif sequence in P60. Anti-P60 antibodies specifically stained the asexual blood
      stages of Plasmodium falciparum and Plasmodium yoelii in an immunofluorescence
      assay, recognized a 60- to 65-kDa parasite protein in an immunoblot assay, and
      blocked P. falciparum merozoite invasion of erythrocytes in a dose-dependent
      manner. Immunization with P60 also induced significant levels of the cytokines
      interleukin-2 (IL-2), IL-4, and gamma interferon in BALB/c mice. Moreover, >60%
      of mice immunized with P60 survived a heterologous challenge infection with a
      lethal strain of P. yoelii. These results indicate that appropriate medium-sized
      synthetic peptides might prove useful in generating specific immune responses to
      an otherwise cryptic but critical and putatively protective epitope in an antigen
      and could form part of a multicomponent malaria vaccine.

PMID- 9632591
TI  - In vitro cellular toxicity predicts Pseudomonas aeruginosa virulence in lung
      infections.
AB  - The role of quorum sensing by Pseudomonas aeruginosa in producing cytotoxicity
      has not been fully investigated. Strains of P. aeruginosa have been characterized
      as having an invasive or a cytotoxic phenotype (S. M. J. Fleiszig et al., Infect.
      Immun. 65:579-586, 1997). We noted that the application of a large inoculum of
      the invasive strain 6294 caused cytotoxicity of cultured epithelial cells. To
      investigate this dose-related cytotoxicity, we compared the behavior of 6294 to
      that of another invasive strain, PAO1, and determined whether the cytotoxicity
      could be related to quorum sensing. Both invasive strains, 6294 and PAO1, appear
      to have quorum-sensing systems that were operative when large doses of bacteria
      were applied to cultured lung epithelial cells or instilled into the lungs of
      animals. Nonetheless, only 6294 was cytotoxic. Cytotoxicity induced by 6294
      correlated with increased elastase production. These experiments suggest that
      there are multiple mechanisms for the induction of cytotoxicity, pathology, and
      mortality in vivo. However, in vivo cytotoxicity and mortality, but not
      pathology, could be predicted by quantitative in vitro cellular damage
      experiments utilizing a range of bacteria-to-cell ratios. It appears that quorum
      sensing may inversely correlate with virulence in that strains that produced PAI
      [N-(3-oxododecanoyl) homoserine lactone] also appeared to attract more
      polymorphonuclear leukocytes in vivo and were possibly eliminated more quickly.
      In addition, exoproduct production in bacteriological medium in vitro may differ
      significantly from exoproduct expression from infections in vivo or during
      cocultivation of bacteria with tissue culture cells.

PMID- 9632592
TI  - Construction and vaccine potential of acapsular mutants of Erysipelothrix
      rhusiopathiae: use of excision of Tn916 to inactivate a target gene.
AB  - We previously showed that acapsular transposon Tn916 mutants of Erysipelothrix
      rhusiopathiae are avirulent for mice. In this study, we constructed nonreverting
      acapsular mutants and examined the vaccine potential of the mutants in mice. A
      representative acapsular transposon mutant, 33H6, was plated on selective agar
      containing autoclaved chlortetracycline and quinaldic acid, and two tetracycline
      sensitive mutants were obtained. Sequence analysis of chromosomal regions of the
      mutants in which Tn916 had flanked revealed that Tn916 had spontaneously excised
      from the region and that the six new nucleotides, which were presumably inserted
      with Tn916 into 33H6 chromosome, substituted for those present at the insertion
      site. The mutants were confirmed to be devoid of capsular antigen by Western
      immunoblotting and were nonvirulent for mice (subcutaneous 50% lethal dose
      [LD50], >10(9) CFU). The safety and efficacy of acapsular mutants for live
      vaccines was further studied by using one mutant strain, named YS-1. The YS-1
      bacteria were cleared from the skin sites of inoculation, livers, and spleens of
      the inoculated mice by 7 days after subcutaneous (s.c.) inoculation. Mice
      immunized s.c. with doses ranging from 2 x 10(4) to 2 x 10(8) CFU of strain YS-1
      were completely protected against challenge with 100 LD50 of the homologous,
      highly virulent strain Fujisawa-SmR 21 days postimmunization, and protective
      immunity conferred by immunization with 2 x 10(8) CFU of the strain lasted for as
      long as the 3 months of the observation period. In passive immunization
      experiments, sera collected from mice immunized with strain YS-1 at days 14 and
      21 postimmunization provided protection against challenge with Fujisawa-SmR,
      whereas sera collected at days 4 and 7 did not. Furthermore, specific spleen cell
      responses to E. rhusiopathiae antigens were observed in mice immunized with
      strain YS-1, and cross-protection against the antigenically heterologous
      bacterium Listeria monocytogenes was observed at 7 days after immunization in the
      mice, suggesting that cell-mediated immunity had been induced. These results
      suggest that E. rhusiopathiae YS-1 may be a suitable choice for further studies
      of vaccine efficacy in swine.

PMID- 9632593
TI  - Potential role of epithelial cell-derived histone H1 proteins in innate
      antimicrobial defense in the human gastrointestinal tract.
AB  - In the human gastrointestinal tract, microorganisms are present in large numbers
      in the colon but are sparse in the proximal small intestine. In this study, we
      have shown that acid extracts of fresh human terminal ileal mucosal samples
      mediate antimicrobial activity. Following cation-exchange chromatography, one of
      the eluted fractions demonstrated antibacterial activity against bacteria
      normally resident in the human colonic lumen. This activity was further
      fractionated by reverse-phase high-performance liquid chromatography and
      identified as histone H1 and its fragments. We have also shown that in tissue
      sections, immunoreactive histone H1 is present in the cytoplasm of villus
      epithelial cells. In vitro culturing of detached (from the basement membrane)
      villus epithelial cells led to the release of antimicrobial histone H1 proteins,
      while the cells demonstrated ultrastructural features of programmed cell death.
      Our studies suggest that cytoplasmic histone H1 may provide protection against
      penetration by microorganisms into villus epithelial cells. Moreover, intestinal
      epithelial cells released into the lumen may mediate antimicrobial activity by
      releasing histone H1 proteins and their fragments.

PMID- 9632594
TI  - Cloning of the gene encoding the 44-kilodalton antigen of the agent of human
      granulocytic ehrlichiosis and characterization of the humoral response.
AB  - Antibodies in the sera of patients with human granulocytic ehrlichiosis (HGE)
      commonly recognize a 44-kDa antigen. We cloned the gene encoding the 44-kDa
      protein of the agent of HGE (aoHGE) by probing an aoHGE lambda ZAP II genomic DNA
      expression library with sera from aoHGE-infected mice. The gene, hge-44, is part
      of a multigene family, with sequence similarity to the Anaplasma marginale msp-2
      genes. RNA-PCR studies confirmed that hge-44 is expressed by aoHGE cultured in HL
      60 cells and by aoHGE during murine infection. Recombinant HGE-44, expressed and
      purified as a glutathione transferase fusion protein, was used as the substrate
      in immunoblots to help diagnose HGE. Antibodies in eight sera from eight patients
      with HGE and in two sera from two aoHGE-infected mice bound recombinant HGE-44.
      Antibodies in the sera of healthy individuals or patients with Ehrlichia
      chaffeensis or Borrelia burgdorferi infection did not recognize HGE-44. We
      conclude that hge-44 is a member of a multigene family and that hge-44 is
      expressed and elicits specific antibodies during infection.

PMID- 9632595
TI  - Protective roles of gamma delta T cells and interleukin-15 in Escherichia coli
      infection in mice.
AB  - The number of gamma delta T cells in the peritoneal cavity was increased after an
      intraperitoneal (i.p.) infection with Escherichia coli in lipopolysaccharide
      (LPS)-responsive C3H/HeN mice but not in LPS-hyporesponsive C3H/HeJ mice. The
      gamma delta T cells preferentially expressed invariant Vgamma6 and Vdelta1 chains
      and proliferated to produce a large amount of gamma interferon in the presence of
      LPS. Mice depleted of gamma delta T cells by T-cell receptor delta gene mutation
      showed impaired resistance against E. coli as assessed by bacterial growth.
      Macrophages from C3H/HeN mice infected with E. coli expressed higher levels of
      interleukin-15 (IL-15) mRNA than those from the infected C3H/HeJ mice.
      Administration of anti-IL-15 monoclonal antibody inhibited, albeit partially, the
      appearance of gamma delta T cells in C3H/HeN mice after E. coli infection and
      diminished the host defense against the infection. These results suggest that LPS
      stimulated gamma delta T cells play an important role in the host defense against
      E. coli infection and that IL-15 may be partly involved in the protection via an
      increase in the gamma delta T cells.

PMID- 9632596
TI  - Human and murine immune responses to a novel Leishmania major recombinant protein
      encoded by members of a multicopy gene family.
AB  - Vaccination of BALB/c mice with Leishmania major promastigote culture filtrate
      proteins plus Corynebacterium parvum confers resistance to infection with L.
      major. To define immunogenic components of this protein mixture, we used sera
      from vaccinated mice to screen an L. major amastigote cDNA expression library.
      One of the immunoreactive clones thus obtained encoded a novel protein of L.
      major with a molecular mass of 22.1 kDa. The predicted amino acid sequence of
      this clone exhibited significant homology to eukaryotic thiol-specific
      antioxidant (TSA) proteins. Therefore, we have designated this protein L. major
      TSA protein. Southern blot hybridization analyses indicate that there are
      multiple copies of the TSA gene in all species of Leishmania analyzed. Northern
      blot analyses demonstrated that the TSA gene is constitutively expressed in L.
      major promastigotes and amastigotes. Recombinant TSA protein containing an amino
      terminal six-histidine tag was expressed in Escherichia coli with the pET17b
      system and was purified to homogeneity by affinity chromatography. Immunization
      of BALB/c mice with recombinant TSA protein resulted in the development of strong
      cellular immune responses and conferred protective immune responses against
      infection with L. major when the protein was combined with interleukin 12. In
      addition, recombinant TSA protein elicited in vitro proliferative responses from
      peripheral blood mononuclear cells of human leishmaniasis patients and
      significant TSA protein-specific antibody titers were detected in sera of both
      cutaneous-leishmaniasis and visceral-leishmaniasis patients. Together, these data
      suggest that the TSA protein may be useful as a component of a subunit vaccine
      against leishmaniasis.

PMID- 9632597
TI  - Expansion of a novel pulmonary CD3(-) CD4(+) CD8(+) cell population in mice
      during Chlamydia pneumoniae infection.
AB  - A new pulmonary T-cell-like lymphocyte population with the phenotype CD3(-)
      CD4(+) CD8(+) was discovered in mice. CD4(+) CD8(+) but CD3(+) cells among murine
      intestinal intraepithelial lymphocytes have previously been described. We
      describe herein a dramatic expansion of the CD3(-) CD4(+) CD8(+) cell population
      in response to experimental respiratory infection. After intranasal Chlamydia
      pneumoniae infection, CD4(+) CD8(+) cells became transiently the dominant
      lymphocyte type (maximum of 87% of all lymphocytes) in the lungs of NIH/S mice
      but remained virtually undetectable in spleen and blood. The enrichment of these
      cells was not a C. pneumoniae-specific event, since infection of NIH/S mice with
      influenza A virus also resulted in an increase in the number of CD4(+) CD8(+)
      cells (maximum of 42% of all lymphocytes). In addition to outbred NIH/S mice, two
      other mouse strains were studied: BALB/c (H-2(d)) and C57BL/6 (H-2(b)). C.
      pneumoniae-infected BALB/c mice responded with an intermediate increase in the
      number of CD4(+) CD8(+) cells in lungs, whereas C57BL/6 mice did not respond. The
      double-positive CD4(+) CD8(+) cells lacked a major part of the T-cell receptor
      complex, being both CD3(-) and TCR alpha beta-. However, when they were
      stimulated in vitro with a T-cell mitogen, they responded by proliferation but
      did not secrete gamma interferon. The dramatic expansion of this cell population
      at the infection site suggests an active role for them in respiratory infection,
      but the specification of this requires further study.

PMID- 9632598
TI  - Bradyzoite development in Toxoplasma gondii and the hsp70 stress response.
AB  - Toxoplasma gondii is a well-described ubiquitous Apicomplexan protozoan parasite
      that is an important opportunistic pathogen. The factors affecting the transition
      of tachyzoites to the latent bradyzoite stage remain to be defined. The induction
      of bradyzoite development in vitro has been linked to temperature, pH,
      mitochondrial inhibitors, sodium arsenite, and many of the other stressors
      associated with heat shock protein (hsp) induction. There is evidence for other
      organisms that hsps are developmentally regulated. Therefore, we examined whether
      hsp induction is an early event in bradyzoite differentiation. Extracellular and
      intracellular T. gondii cells, after exposure to pH 8.1 or 7.1, were analyzed for
      the expression of inducible hsp70 by using monoclonal antibody C92F3A-5 (specific
      to hsp70). Western blotting demonstrated that a 72-kDa protein reactive with
      C92F3A-5 (hsp70), which we believe is part of the hsp70 family, is induced during
      bradyzoite development. By immunofluorescence and immunoelectron microscopy, we
      were able to demonstrate that hsp70 staining colocalized to T. gondii expressing
      bradyzoite-specific antigens and the presence of hsp70 in bradyzoites isolated
      from mouse brain. Quercetin, a bioflavonoid which inhibits the synthesis of
      hsp90, hsp70, and hsp27, suppresses the induction of bradyzoite development in
      vitro. Reverse transcription-PCR with conserved hsp70 primers demonstrated an
      increase in hsp70 in T. gondii on exposure to conditions which induce bradyzoite
      formation. A T. gondii hsp70 was subsequently cloned and sequenced by using this
      amplified fragment. We believe our evidence suggests that hsps are important in
      the process of bradyzoite differentiation.

PMID- 9632600
TI  - Intestinal immune responses to an inactivated oral enterotoxigenic Escherichia
      coli vaccine and associated immunoglobulin A responses in blood.
AB  - An inactivated oral enterotoxigenic Escherichia coli (ETEC) vaccine against ETEC
      diarrhea was given to 25 adult Swedish volunteers. The vaccine consisted of
      formalin-killed E. coli bacteria expressing the most common colonization factor
      antigens (CFAs), i.e., CFA/I, -II, and -IV, and recombinantly produced cholera B
      subunit (CTB). Immunoglobulin A (IgA) antibody responses in intestinal lavage
      fluid to CTB and CFAs were determined and compared with corresponding responses
      in stool extracts and serum as well as with IgA antibody-secreting cell (ASC)
      responses in peripheral blood. Two doses of vaccine induced significant IgA
      responses to the different CFAs in lavage fluid in 61 to 87% of the vaccinees and
      in stool in 38 to 81% of them. The most frequent responses were seen against
      CFA/I. The magnitudes of the antibody responses against CTB and CFA/I in stool
      correlated significantly (CTB, P < 0.01; CFA/I, P < 0. 05) with those in
      intestinal lavage. Intestinal lavage responses against CFAs were best reflected
      by the ASC responses, with the sensitivity of the ASC assay being 80 to 85%,
      followed by stool (sensitivity of 50 to 88%) and serum antibody (sensitivity of 7
      to 65%) analyses. CTB-specific immune responses were seen in >90% of the
      vaccinees in all assays.

PMID- 9632599
TI  - In vivo phase variation of Escherichia coli type 1 fimbrial genes in women with
      urinary tract infection.
AB  - Type 1 fimbriae, expressed by most Escherichia coli strains, are thought to
      attach to human uroepithelium as an initial step in the pathogenesis of urinary
      tract infections (UTI). Numerous reports using both in vitro and murine models
      support this role for type 1 fimbriae in colonization. Unfortunately, only a
      limited number of studies have directly examined the expression of fimbriae in
      vivo. To determine whether type 1 fimbrial genes are transcribed during an acute
      UTI, we employed a modification of an established method. The orientation (ON or
      OFF) of the invertible promoter element, which drives transcription of type 1
      fimbrial genes, was determined by PCR amplification using primers that flank the
      invertible element, followed by SnaBI digestion. The orientation of the type 1
      fimbrial switch was determined under three experimental conditions. First, E.
      coli strains from different clinical sources (acute pyelonephritis patients,
      cystitis patients, and fecal controls) were tested under different in vitro
      culture conditions (agar versus broth; aerated versus static). The genes in the
      more-virulent strains (those causing acute pyelonephritis) demonstrated a
      resistance, in aerated broth, to switching from OFF to ON, while those in fecal
      strains readily switched from OFF to ON. Second, bladder and kidney tissue from
      CBA mice transurethrally inoculated with E. coli CFT073 (an established murine
      model of ascending UTI) was assayed. The switches directly amplified from
      infected bladder and kidney tissues were estimated to be 33 and 39% ON,
      respectively, by using a standard curve. Finally, bacteria present in urine
      samples collected from women with cystitis were tested for type 1 fimbria switch
      orientation. For all 11 cases, an average of only 4% of the switches in the
      bacteria in the urine were ON. In 7 of the 11 cases, we found that all of the
      visible type 1 fimbrial switches were in the OFF position (upper limit of
      detection of assay, 98% OFF). Strains recovered from these urine samples,
      however, were shown after culture in vitro to be capable of switching the
      fimbrial gene to the ON position and expressing mannose-sensitive hemagglutinin.
      The results from experimental infections and cases of cystitis in women suggest
      that type 1 fimbrial genes are transcribed both in the bladder and in the kidney.
      However, those bacteria found in the urine and not attached to the uroepithelium
      are not transcriptionally active for type 1 fimbrial genes.

PMID- 9632601
TI  - The pH of the host niche controls gene expression in and virulence of Candida
      albicans.
AB  - Little is known of the biological attributes conferring pathogenicity on the
      opportunistic fungal pathogen Candida albicans. Infection by this pathogen, as
      for bacterial pathogens, may rely upon environmental signals within the host
      niche to regulate the expression of virulence determinants. To determine if C.
      albicans responds to the pH of the host niche, we tested the virulence of strains
      with mutations in either of two pH-regulated genes, PHR1 and PHR2. In vitro, PHR1
      is expressed when the ambient pH is at 5.5 or higher and deletion of the gene
      results in growth and morphological defects at neutral to alkaline pHs.
      Conversely, PHR2 is expressed at an ambient pH below 5.5, and the growth and
      morphology of the null mutant is compromised below this pH. A PHR1 null mutant
      was avirulent in a mouse model of systemic infection but uncompromised in its
      ability to cause vaginal infection in rats. Since systemic pH is near neutrality
      and vaginal pH is around 4.5, the virulence phenotype paralleled the pH
      dependence of the in vitro phenotypes. The virulence phenotype of a PHR2 null
      mutant was the inverse. The mutant was virulent in a systemic-infection model but
      avirulent in a vaginal-infection model. Heterozygous mutants exhibited partial
      reductions in their pathogenic potential, suggesting a gene dosage effect.
      Unexpectedly, deletion of PHR2 did not prevent hyphal development in vaginal
      tissue, suggesting that it is not essential for hyphal development in this host
      niche. The results suggest that the pH of the infection site regulates the
      expression of genes essential to survival within that niche. This implies that
      the study of environmentally regulated genes may provide a rationale for
      understanding the pathobiology of C. albicans.

PMID- 9632602
TI  - Cloning and mutagenesis of a serotype-specific DNA region involved in
      encapsulation and virulence of Actinobacillus pleuropneumoniae serotype 5a:
      concomitant expression of serotype 5a and 1 capsular polysaccharides in
      recombinant A. pleuropneumoniae serotype 1.
AB  - A DNA region involved in Actinobacillus pleuropneumoniae serotype 5 capsular
      polysaccharide (CP) biosynthesis was identified and characterized by using a
      probe specific for the cpxD gene involved in CP export. The adjacent serotype 5
      specific CP biosynthesis region was cloned from a 5.8-kb BamHI fragment and an
      8.0-kb EcoRI fragment of strain J45 genomic DNA. DNA sequence analysis
      demonstrated that this region contained four complete open reading frames, cps5A,
      cps5B, cps5C, and cps5D. Cps5A, Cps5B, and Cps5C showed low homology with several
      bacterial glycosyltransferases involved in the biosynthesis of lipopolysaccharide
      or CP. However, Cps5D had high homology with KdsA proteins (3-deoxy-D-manno-2
      octulosonic acid 8-phosphate synthetase) from other gram-negative bacteria. The
      G+C content of cps5ABC was substantially lower (28%) than that of cps5D and the
      rest of the A. pleuropneumoniae chromosome (42%). A 2.1-kb deletion spanning the
      cloned cps5ABC open reading frames was constructed and transferred into the J45
      chromosome by homologous recombination with a kanamycin resistance cassette to
      produce mutant J45-100. Multiplex PCR confirmed the deletion in this region of
      J45-100 DNA. J45-100 did not produce intracellular or extracellular CP,
      indicating that cps5A, cps5B, and/or cps5C were involved in CP biosynthesis.
      However, biosynthesis of the Apx toxins, lipopolysaccharide, and membrane
      proteins was unaffected by the mutation. Besides lack of CP biosynthesis, and in
      contrast to J45, J45-100 grew faster, was sensitive to killing in precolostral
      calf serum, and was avirulent in pigs at an intratracheal challenge dose three
      times the 50% lethal dose (LD50) of strain J45. At six times the J45 LD50, J45
      100 caused mild to moderate lung lesions but not death. Electroporation of
      cps5ABC into A. pleuropneumoniae serotype 1 strain 4074 generated strain
      4074(pJMLCPS5), which expressed both serotype 1 and serotype 5 CP. However,
      serotype 1 capsule expression was diminished in 4074(pJMLCPS5) in comparison to
      4074. The recombinant strain produced significantly less total CP (serotypes 1
      and 5 CP combined) in log phase (P = 0.0012) but significantly more total CP in
      late stationary phase than 4074 (P < 0.0001). In addition, strain 4074(pJMLCPS5)
      caused less mortality and bacteremia in pigs and mice following respiratory
      challenge than strain 4074, indicating that virulence was affected by diminished
      capsule production. These results emphasize the importance of CP in the serum
      resistance and virulence of A. pleuropneumoniae.

PMID- 9632603
TI  - Identification and characterization of staphylococcal enterotoxin types G and I
      from Staphylococcus aureus.
AB  - Staphylococcal enterotoxins are exotoxins produced by Staphylococcus aureus that
      possess emetic and superantigenic properties. Prior to this research there were
      six characterized enterotoxins, staphylococcal enterotoxin types A to E and H
      (referred to as SEA to SEE and SEH). Two new staphylococcal enterotoxin genes
      have been identified and designated seg and sei (staphylococcal enterotoxin types
      G and I, respectively). seg and sei consist of 777 and 729 nucleotides,
      respectively, encoding precursor proteins of 258 (SEG) and 242 (SEI) deduced
      amino acids. SEG and SEI have typical bacterial signal sequences that are cleaved
      to form toxins with 233 (SEG) and 218 (SEI, predicted) amino acids, corresponding
      to mature proteins of 27,043 Da (SEG) and 24,928 Da (SEI). Biological activities
      for SEG and SEI were determined with recombinant S. aureus strains. SEG and SEI
      elicited emetic responses in rhesus monkeys upon nasogastric administration and
      stimulated murine T-cell proliferation with the concomitant production of
      interleukin 2 (IL-2) and gamma interferon (IFN-gamma), as measured by cytokine
      enzyme-linked immunoassays. SEG and SEI are related to other enterotoxins of S.
      aureus and to streptococcal pyrogenic exotoxin A (SpeA) and streptococcal
      superantigen (SSA) of Streptococcus pyogenes. Phylogenetic analysis and
      comparisons of amino acid and nucleotide sequence identities were performed on
      related staphylococcal and streptococcal protein toxins to group SEG and SEI
      among the characterized toxins. SEG is most similar to SpeA, SEB, SEC, and SSA
      (38 to 42% amino acid identity), while SEI is most similar to SEA, SEE, and SED
      (26 to 28% amino acid identity). Polyclonal antiserum was generated against
      purified histidine-tagged SEG and SEI (HisSEG and HisSEI). Immunoblot analysis of
      the enterotoxins, toxic-shock syndrome toxin 1, and SpeA with antiserum prepared
      against HisSEG and HisSEI revealed that SEG shares some epitopes with SEC1 while
      SEI does not.

PMID- 9632604
TI  - A 20-kilodalton N-terminal fragment of the D15 protein contains a protective
      epitope(s) against Haemophilus influenzae type a and type b.
AB  - A conserved 80-kDa minor outer membrane protein, D15, of Haemophilus influenzae
      has been shown to be a protective antigen in laboratory animals against H.
      influenzae type a (Hia) or type b (Hib) infection. To localize the protective B
      cell epitope(s) within the D15 protein and to further explore the possibility of
      using synthetic peptides as vaccine antigens, a 20-kDa N-terminal fragment of D15
      protein (truncated D15 [tD15]) was expressed as a fusion protein with glutathione
      S-transferase in Escherichia coli. The tD15 moiety was cleaved from glutathione S
      transferase by using thrombin and purified to homogeneity. The purified soluble
      tD15 appeared to contain immunodominant protective epitope(s) against Hia and
      Hib, since rabbit antisera directed against tD15 were capable of protecting
      infant rats from Hia or Hib bacteremia. The ease of purification of soluble tD15,
      therefore, makes it a better candidate antigen than the full-length recombinant
      D15 which is produced as inclusion bodies in E. coli. Furthermore, both the
      purified tD15 fragment and a mixture of tD15-derived peptides spanning amino acid
      residues 93 to 209 of the mature D15 protein were capable of inhibiting the
      protection against Hib conferred on infant rats by rabbit anti-tD15 antiserum,
      indicating that the protective epitopes of D15 may not be conformational.
      However, the administration of pooled rabbit immune sera raised against the same
      panel of peptides failed to protect infant rats from Hib infection.

PMID- 9632605
TI  - Susceptibility to Salmonella typhimurium infection and effectiveness of
      vaccination in mice deficient in the tumor necrosis factor alpha p55 receptor.
AB  - Mice defective in the ability to produce the tumor necrosis factor alpha p55
      receptor (TNFalphap55R) were orally challenged with a number of Salmonella
      typhimurium HWSH derivatives that differ in virulence. In comparison to
      TNFalphap55R+/+ mice, TNFalphap55R-/- mice succumbed earlier to challenge with
      wild-type S. typhimurium HWSH and S. typhimurium HWSH purE. In contrast,
      TNFalphap55R-/- mice were able to control an S. typhimurium HWSH aroA challenge,
      although greater numbers of Salmonella organisms were present in the tissues for
      a longer time period than was observed with TNFalphap55R+/+ mice. Vaccination of
      normal and TNFalphap55R knockout animals with S. typhimurium HWSH aroA showed
      that TNFalphap55R-/- mice, unlike TNFalphap55R+/+ mice, were not protected
      against a virulent S. typhimurium HWSH challenge. Splenocytes from TNFalphap55R-/
      mice exhibited a reduced ability to proliferate in the presence of S.
      typhimurium antigen compared to TNFalphap55R+/+ mice. Thus, TNFalphap55R is
      essential for controlling Salmonella growth in tissues and for recall of immunity
      in murine salmonellosis.

PMID- 9632606
TI  - Identification and sequence analysis of a 27-kilobase chromosomal fragment
      containing a Salmonella pathogenicity island located at 92 minutes on the
      chromosome map of Salmonella enterica serovar typhimurium LT2.
AB  - Using a genomic approach, we have identified a new Salmonella pathogenicity
      island, SPI-4, which is the fourth Salmonella pathogenicity island to be
      identified. SPI-4 was located at 92 min on the chromosome map and was flanked by
      the ssb and soxSR loci. The DNA sequence covering the entire SPI-4 and both
      boundaries was determined. The size of SPI-4 was about 25 kb and it contains 18
      putative open reading frames (ORFs). Three of these ORFs encode proteins that
      have significant homology with proteins involved in toxin secretion. Another five
      ORFs encode proteins that have significant homology with hypothetical proteins
      from Synechocystis sp. strain PCC6803 or Acinetobacter calcoaceticus. The rest of
      the ORFs encode novel proteins, one of which has five membrane-spanning domains.
      SPI-4 is likely to carry a type I secretion system involved in toxin secretion.
      Furthermore, a previously identified locus (ims98), which is required for
      intramacrophage survival, was also mapped within the SPI-4 region. These findings
      suggested that SPI-4 is needed for intramacrophage survival.

PMID- 9632607
TI  - At least four percent of the Salmonella typhimurium genome is required for fatal
      infection of mice.
AB  - Salmonella typhimurium infection of mice is an established model system for
      studying typhoid fever in humans. Using this model, we identified S. typhimurium
      genes which are absolutely required to cause fatal murine infection by testing
      independently derived transposon insertion mutants for loss of virulence in vivo.
      Of the 330 mutants tested intraperitoneally and the 197 mutants tested
      intragastrically, 12 mutants with 50% lethal doses greater than 1, 000 times that
      of the parental strain were identified. These attenuated mutants were
      characterized by in vitro assays which correlate with known virulence functions.
      In addition, the corresponding transposon insertions were mapped within the S.
      typhimurium genome and the nucleotide sequence of the transposon-flanking DNA was
      obtained. Salmonella spp. and related bacteria were probed with flanking DNA for
      the presence of these genes. All 12 attenuated mutants had insertions in known
      genes, although the attenuating effects of only two of these were previously
      described. Furthermore, the proportion of attenuated mutants obtained in this
      study suggests that mutations in about 4% of the Salmonella genome lead to 1,000
      fold or greater attenuation in the mouse typhoid model of infection. Most of
      these genes appear to be required during the early stages of a natural infection.

PMID- 9632608
TI  - Identification of three highly attenuated Salmonella typhimurium mutants that are
      more immunogenic and protective in mice than a prototypical aroA mutant.
AB  - A panel of Salmonella typhimurium 14028s mutants, which were previously shown to
      be highly attenuated in the BALB/c mouse model of infection, were analyzed for
      their potential as live Salmonella oral-vaccine candidates. A prototypical aroA
      mutant was chosen as a basis of comparison. From the panel of mutants initially
      chosen for this study, three mutants with comparable levels of attenuation
      elicited higher Salmonella-specific serum immunoglobulin G (IgG) and/or mucosal
      secretory-IgA antibody titers than the aroA vaccine strain. The three mutants,
      CL288, CL401, and CL554, also elicited a better protective immune response than
      the aroA control strain, after a single oral dose of 1 x 10(9) to 2 x 10(9)
      bacteria.

PMID- 9632609
TI  - Cytotoxicity of hemolytic, cytotoxic necrotizing factor 1-positive and -negative
      Escherichia coli to human T24 bladder cells.
AB  - Approximately one-half of Escherichia coli isolates from patients with cystitis
      or pyelonephritis produce the pore-forming cytotoxin hemolysin, a molecule with
      the capacity to lyse erythrocytes and a range of nucleated cell types. A second
      toxin, cytotoxic necrotizing factor 1 (CNF1), is found in approximately 70% of
      hemolytic, but rarely in nonhemolytic, isolates. To evaluate the potential
      interplay of these two toxins, we used epidemiological and molecular biologic
      techniques to compare the cytotoxicity of hemolytic, CNF1(+), and CNF1(-)
      cystitis strains toward human T24 bladder epithelial cells in vitro. A total of
      29 isolates from two collections of cystitis-associated E. coli were evaluated by
      using methylene blue staining of bladder monolayers at 1-h intervals after
      inoculation with each strain. Most (20 of 29) isolates damaged or destroyed the
      T24 monolayer (less than 50% remaining) within 4 h after inoculation. As a group,
      CNF1(+) isolates from one collection (11 strains) were less cytotoxic at 4 h than
      the CNF1(-) strains in that collection (P = 0.009), but this pattern was not
      observed among isolates from the second collection (18 strains). To directly
      evaluate the role of CNF1 in cytotoxicity of hemolytic E. coli without the
      variables present in multiple clinical isolates, we constructed mutants defective
      in production of CNF1. Compared to the CNF1(+) parental isolates, no change in
      cytotoxicity was detected in these cnf1 mutants. Our results indicate that CNF1
      does not have a detectable effect on the ability of hemolytic E. coli to damage
      human bladder cell monolayers in vitro.

PMID- 9632610
TI  - Differential kinetics and distribution of antibodies in serum and nasal and
      vaginal secretions after nasal and oral vaccination of humans.
AB  - Although nasal vaccination has emerged as an interesting alternative to systemic
      or oral vaccination, knowledge is scarce about the immune responses after such
      immunization in humans. In the present study, we have compared the kinetics and
      organ distribution of the antibody responses after nasal and oral vaccination. We
      immunized female volunteers nasally or orally with cholera toxin B subunit (CTB)
      and determined the specific antibody levels in serum and nasal and vaginal
      secretions, as well as the number of circulating antibody-secreting cells, before
      immunization and 1, 2, 3, 6, and 26 weeks thereafter. Nasal vaccination induced 9
      fold CTB-specific immunoglobulin A (IgA) and 56-fold specific IgG antibody
      increases in nasal secretions, whereas no significant IgA increase was seen after
      oral vaccination. Both oral and nasal vaccination resulted in 5- to 6-fold CTB
      specific IgA and 20- to 30-fold specific IgG increases in vaginal secretions.
      Strong serum responses to CTB were also induced by both routes of vaccination. A
      notable difference between nasal and oral vaccination was that the nasal route
      elicited a specific antibody response with a later onset but of much longer
      duration than did the oral route. We conclude from this study that the nasal
      route is superior to the oral route for administering at least nonliving vaccines
      against infections in the upper respiratory tract, whereas either oral or nasal
      vaccination might be used for eliciting antibody responses in the female genital
      tract.

PMID- 9632611
TI  - Inhibition of binding of malaria-infected erythrocytes by a tetradecasaccharide
      fraction from chondroitin sulfate A.
AB  - Adherence of parasite-infected erythrocytes (IEs) to the microvascular
      endothelium of various organs, a process known as sequestration, is a feature of
      Plasmodium falciparum malaria. This event is mediated by specific adhesive
      interactions between parasite proteins, expressed on the surface of IEs, and host
      molecules. P. falciparum IEs can bind to purified chondroitin sulfate A (CS-A),
      to the proteoglycan thrombomodulin through CS-A side chains, and to CS-A present
      on the surface of brain and lung endothelial cells and placental
      syncytiotrophoblasts. In order to identify structural characteristics of CS-A
      important for binding, oligosaccharide fragments ranging in size from 2 to 20
      monosaccharide units were isolated from CS-A and CS-C, following controlled
      chondroitin lyase digestion, and used as competitive inhibitors of IE binding to
      immobilized ligands. Inhibition of binding to CS-A was highly dependent on
      molecular size: a CS-A tetradecasaccharide fraction was the minimum length able
      to almost completely inhibit binding. The effect was dose dependent and similar
      to that of the parent polysaccharide, and the same degree of inhibition was not
      found with the CS-C oligosaccharides. There was no effect on binding of IEs to
      other ligands, e.g., CD36 and intercellular adhesion molecule 1. Hexadeca- and
      octadecasaccharide fractions of CS-A were required for maximum inhibition of
      binding to thrombomodulin. Analyses of oligosaccharide fractions and
      polysaccharides by electrospray mass spectrometry and high-performance liquid
      chromatography suggest that the differences between the activities of CS-A and CS
      C oligosaccharides can be attributed to differences in sulfate content and
      sulfation pattern and that iduronic acid is not involved in IE binding.

PMID- 9632612
TI  - Low genetic diversity of Haemophilus influenzae type b compared to
      nonencapsulated H. influenzae in a population in which H. influenzae is highly
      endemic.
AB  - Immunization with Haemophilus influenzae type b (Hib) conjugate polysaccharide
      vaccines has dramatically reduced Hib disease worldwide. As in other populations,
      nasopharyngeal carriage of Hib declined markedly in Aboriginal infants following
      vaccination, although carriage has not been entirely eliminated. In this study,
      we describe the genetic characteristics and the carriage dynamics of longitudinal
      isolates of Hib, characterized by using several typing methods. In addition,
      carriage rates of nonencapsulated H. influenzae (NCHi) are high, and concurrent
      colonization with Hib and NCHi is common; we also observed NCHi isolates which
      were genetically similar to Hib. There is a continuing need to promote Hib
      immunization and monitor H. influenzae carriage in populations in which the
      organism is highly endemic, not least because of the possibility of genetic
      exchange between Hib and NCHi strains in such populations.

PMID- 9632613
TI  - Monocytic differentiation inhibits infection and granulocytic differentiation
      potentiates infection by the agent of human granulocytic ehrlichiosis.
AB  - Human granulocytic ehrlichiosis (HGE) is an emerging tick-borne infection with a
      specific tropism for granulocytes. We previously isolated and cultivated the HGE
      agent in the promyelocytic leukemia cell line HL-60 and have also demonstrated
      the susceptibility of both granulocytic and monocytic human marrow progenitors.
      Circulating monocytes have not been observed to be infected, suggesting that cell
      susceptibility may be differentiation specific. To evaluate this hypothesis, HL
      60 cells were differentiated towards granulocytes (with dimethyl sulfoxide or all
      trans retinoic acid) or toward monocytes-macrophages (with 12-O
      tetradecanoylphorbol-13-acetate [TPA], gamma interferon, or 1, 25
      dihydroxyvitamin D3) and then challenged with HGE. HGE binding, internalization,
      and proliferation were compared in differentiated and untreated control HL-60
      cells by immunofluorescence, electron microscopy, and Giemsa staining.
      Granulocytic differentiation resulted in a doubling of HGE binding and enhanced
      infection consistent with the agent's clinical tropism for neutrophils.
      Granulocytic cells were unable to kill internalized ehrlichiae even after
      activation induced by N-formyl-Met-Leu-Phe alone or together with tumor necrosis
      factor alpha. In contrast, monocyte-macrophage differentiation with TPA resulted
      in complete resistance to infection through at least two distinct mechanisms: (i)
      reduction in binding and uptake and (ii) killing of any internalized organisms.
      Diminished binding in TPA-treated cells correlated with their reduced expression
      of sialyl Lewis x (CD15s), a putative cellular receptor component for HGE. The
      degree of monocytic differentiation and activation induced (i.e., TPA > gamma
      interferon > vitamin D3) correlated with resistance to HGE. Thus, HL-60 cells
      exhibit a striking differentiation-specific susceptibility to HGE.
      Differentiation-induced changes in bacterial adhesion and killing capacity
      underlie the tropism of HGE for granulocytic HL-60 cells and, conversely, the
      resistance of activated macrophages to infection.

PMID- 9632614
TI  - Neisseria gonorrhoeae induces focal polymerization of actin in primary human
      urethral epithelium.
AB  - The pathogenic Neisseria species induce cytoskeletal reorganization in
      immortalized cell lines. In Chang conjunctival epithelium and T84 intestinal
      epithelium, focal cytoskeletal rearrangements in which bacteria contacted the
      epithelial surface were observed. We show that actin footprints are induced in
      gonococcus-challenged primary urethral epithelium. Moreover, the microbes induced
      microvillus extension from the epithelial cell surface. Our results indicate that
      formation of actin footprints is not an artifact of commonly used immortalized
      cell lines.

PMID- 9632615
TI  - The inlA gene of Listeria monocytogenes LO28 harbors a nonsense mutation
      resulting in release of internalin.
AB  - Internalin is a surface protein that mediates entry of Listeria monocytogenes EGD
      into epithelial cells expressing the cell adhesion molecule human E-cadherin or
      its chicken homolog, L-CAM, which act as receptors for internalin. After
      observing that entry of L. monocytogenes LO28 into S180 fibroblasts, in contrast
      to that of EGD, did not increase after transfection with L-CAM, we examined both
      the expression and the structure of internalin in strain LO28. We discovered a
      nonsense mutation in inlA which results in a truncated protein released in the
      culture medium. Mutations leading to release of internalin were also detected in
      clinical and food isolates. These results question the role of internalin as a
      virulence factor in murine listeriosis.

PMID- 9632616
TI  - Immunogenicity of four Plasmodium falciparum preerythrocytic antigens in Aotus
      lemurinus monkeys.
AB  - Aotus lemurinus monkeys were immunized with pools of either lipid-tailed peptides
      injected in PBS or peptides in Montanide ISA-51, all derived from four Plasmodium
      falciparum pre-erythrocytic antigens, namely, LSA1, LSA3, SALSA, and STARP. These
      formulations were well tolerated. Their immunogenicity was demonstrated by the
      induction of both B- and T-cell responses to most of the peptides studied (of the
      12, 10 induced antibody production, 9 induced T-cell proliferative responses, and
      all 12 induced gamma interferon secretion). Immune responses proved to be long
      lasting, since some were still detectable 210 days after immunization. Of
      particular importance is the fact that B- and T-cell responses elicited in this
      way by synthetic peptides were specific for native parasite proteins on P.
      falciparum sporozoites and liver stage parasites.

PMID- 9632617
TI  - Attachment of Cryptosporidium parvum sporozoites to human intestinal epithelial
      cells.
AB  - An enzyme-linked immunosorbent assay-based attachment model using the human
      intestinal cell line Caco-2A was developed to study attachment of Cryptosporidium
      parvum sporozoites in vitro and to assess potential inhibitors of sporozoite
      binding. In this system, attachment was related to sporozoite dose, incubation
      time, and host cell differentiation status. Polyclonal antibodies to C. parvum as
      well as glycoprotein inhibitors of a sporozoite lectin reduced attachment. This
      model will be a valuable tool in elucidating specific molecules and mechanisms
      involved in sporozoite-host cell attachment.

PMID- 9632618
TI  - Tube phagocytosis, a novel way for neutrophils to Phagocytize borrelia
      burgdorferi.
AB  - Interactions between human neutrophils and Borrelia burgdorferi, the Lyme disease
      spirochete, were studied by dark-field microscopy combined with video technology.
      A previously unrecognized mechanism for neutrophils to phagocytize the spirochete
      was discovered. During phagocytosis, the spirochete attaches to the neutrophil
      head-on, the neutrophil forms a thin tubelike protrusion around the bacterium,
      and the fully covered spirochete is drawn into the cell.

PMID- 9632619
TI  - Characterization of MGC2, a Mycoplasma gallisepticum cytadhesin with homology to
      the Mycoplasma pneumoniae 30-kilodalton protein P30 and Mycoplasma genitalium
      P32.
AB  - A second cytadhesin-like protein, MGC2, was identified in the avian respiratory
      pathogen Mycoplasma gallisepticum. The 912-nucleotide mgc2 gene encodes a 32.6
      kDa protein with 40.9 and 31.4% identity with the M. pneumoniae P30 and M.
      genitalium P32 cytadhesins, respectively. Functional studies with reverse
      transcription-PCR, immunoblotting, double-sided immunogold labeling, and
      attachment inhibition assays demonstrated homology to the human mycoplasmal P30
      and P32 cytadhesins. These findings suggest that there is a family of cytadhesin
      genes conserved among pathogenic mycoplasmas infecting widely divergent hosts.

PMID- 9632620
TI  - Susceptibility of epithelial cells to Pseudomonas aeruginosa invasion and
      cytotoxicity is upregulated by hepatocyte growth factor.
AB  - Normal cell polarity protects epithelial cells against Pseudomonas aeruginosa
      invasion and cytotoxicity. Using epithelial cell clones with selective defects in
      sorting of membrane constituents, and using hepatocyte growth factor
      pretreatment, we found that polarized susceptibility to P. aeruginosa can be
      altered without disrupting tight junctions. The results also showed that cellular
      susceptibility factors for invasion and cytotoxicity are not the same, although
      both are localized to the basolateral cell surface in polarized epithelial cells.

PMID- 9632621
TI  - Study of immunization against anthrax with the purified recombinant protective
      antigen of Bacillus anthracis.
AB  - Protective antigen (PA) of anthrax toxin is the major component of human anthrax
      vaccine. Currently available human vaccines in the United States and Europe
      consist of alum-precipitated supernatant material from cultures of toxigenic,
      nonencapsulated strains of Bacillus anthracis. Immunization with these vaccines
      requires several boosters and occasionally causes local pain and edema. We
      previously described the biological activity of a nontoxic mutant of PA expressed
      in Bacillus subtilis. In the present study, we evaluated the efficacy of the
      purified mutant PA protein alone or in combination with the lethal factor and
      edema factor components of anthrax toxin to protect against anthrax. Both mutant
      and native PA preparations elicited high anti-PA titers in Hartley guinea pigs.
      Mutant PA alone and in combination with lethal factor and edema factor completely
      protected the guinea pigs from B. anthracis spore challenge. The results suggest
      that the mutant PA protein may be used to develop an effective recombinant
      vaccine against anthrax.

PMID- 9632622
TI  - Identification of an insertion sequence located in a region encoding virulence
      factors of Streptococcus pyogenes.
AB  - An insertion sequence, IS1562, was identified in a Streptococcus pyogenes strain
      of the clinically important M1 serotype. IS1562 is located in the mga regulon
      between the genes coding for the M protein and the C5a peptidase, both important
      virulence factors. The same or similar insertion sequences were found in most S.
      pyogenes strains, but the chromosomal location differed among isolates.

PMID- 9632623
TI  - Delayed-type hypersensitivity responses to ESAT-6 and MPT64 from Mycobacterium
      tuberculosis in the guinea pig.
AB  - Two antigens from Mycobacterium tuberculosis, ESAT-6 and MPT64, elicited delayed
      type hypersensitivity (DTH) skin responses in outbred guinea pigs infected with
      M. tuberculosis by the aerosol and intravenous routes but not those sensitized
      with M. bovis BCG or M. avium. The DTH epitope of ESAT-6 was mapped to the C
      terminus. Nonresponders to the individual antigens were found, but all animals
      responded to a combination of ESAT-6 and MPT64 or their respective minimal target
      peptides. Correspondingly, these molecules could form the basis of a new skin
      test for tuberculosis.

PMID- 9632625
TI  - Bartonella henselae invasion of feline erythrocytes in vitro.
AB  - Bartonella henselae, the causative agent of cat scratch disease, establishes long
      term bacteremia in cats, in which it attaches to and invades feline erythrocytes
      (RBC). Feline RBC invasion was assessed in vitro, based on gentamicin selection
      for intracellular bacteria or by laser confocal microscopy and digital
      sectioning. Invasion rates ranged from 2 to 20% of the inoculum, corresponding to
      infection of less than 1% of the RBC. Invasion was a slow process, requiring >8 h
      before significant numbers of intracellular bacteria were detected. Pretreatment
      of the bacteria with trypsin, or of the RBC with trypsin or neuraminidase, had no
      effect, but pronase pretreatment of RBC resulted in a slight increase in invasion
      frequency. The ability to model B. henselae invasion of feline RBC in vitro
      should permit identification of bacterial surface components involved in this
      process and elucidate the significance of RBC invasion to transmission and
      infection in cats.

PMID- 9632626
TI  - Nonspecific early protective immunity in Francisella and Listeria infections can
      be dependent on lymphocytes.
AB  - Normal mice, but not lymphocyte-deficient or B-cell-deficient mice, given a
      sublethal infection of Francisella tularensis LVS survive a secondary lethal
      challenge of more than 10,000 50% lethal doses given 3 days later. In this work,
      we show that similar early protection that is also strongly lymphocyte dependent
      operates in Listeria monocytogenes infection. Since sublethal infection with
      either LVS or L. monocytogenes protects against heterologous lethal challenge,
      this early protection is nonspecific.

PMID- 9632624
TI  - Protection of mice against Plasmodium yoelii sporozoite challenge with P. yoelii
      merozoite surface protein 1 DNA vaccines.
AB  - Immunization of mice with DNA vaccines encoding the full-length form and C and N
      termini of Plasmodium yoelii merozoite surface protein 1 provided partial
      protection against sporozoite challenge and resulted in boosting of antibody
      titers after challenge. In C57BL/6 mice, two DNA vaccines provided protection
      comparable to that of recombinant protein consisting of the C terminus in
      Freund's adjuvant.

PMID- 9632627
TI  - Multigene families encoding the major hemagglutinins in phylogenetically distinct
      mycoplasmas.
AB  - Mycoplasma synoviae has two major membrane antigens, MSPA and MSPB, both of which
      are phase variable and which may be coordinately involved in adhesion of the
      organism to erythrocytes. A single gene (vlhA) from M. synoviae was
      characterized, and polypeptides were expressed from nonoverlapping 5' and 3'
      regions in Escherichia coli. The expression product of the vlhA 5' region reacted
      with specific reagents against MSPB, while that of the 3' region reacted with
      specific reagents against MSPA. Analysis of the predicted amino acid sequence
      showed a characteristic signal peptidase II cleavage site, and the presence of
      the acylation site was confirmed by identification of a lipid-associated membrane
      protein, similar in molecular mass to MSPB, in [3H]palmitate-labelled membrane
      proteins. Further sequence analysis of the vlhA gene revealed a high identity
      with the Mycoplasma gallisepticum pMGA1.7 gene, a member of a large translated
      family. The vlhA gene was shown to hybridize to multiple restriction fragments of
      the M. synoviae genome, suggesting that it was also a member of a multigene
      family. These findings indicate that coordinate phase variation of the two major
      surface antigens of M. synoviae WVU may be due to their expression from the same
      gene and that homologous gene families encode the major hemagglutinins of two
      phylogenetically distinct mycoplasmas. The presence of homologous multigene
      families in such phylogenetically distinct species, but not in the genomes of
      more closely related species, suggests that the families may have been
      transferred horizontally.

PMID- 9632628
TI  - In vitro resistance to thrombin-induced platelet microbicidal protein is
      associated with enhanced progression and hematogenous dissemination in
      experimental Staphylococcus aureus infective endocarditis.
AB  - We examined the influence of thrombin-induced platelet microbicidal protein 1
      (tPMP-1) on the progression and hematogenous dissemination of experimental
      endocarditis caused by isogenic Staphylococcus aureus strains differing in tPMP
      susceptibility (tPMPs) or resistance (tPMPr) in vitro. Following simultaneous
      challenge of animals with both strains, significantly higher tPMPr bacterial
      densities were present in vegetations (P < 0.0001), kidneys (P < 0. 0001), and
      spleens (P < 0.0001) compared with those for the tPMPs strain. These data
      indicate that tPMP-1 limits the intravegetation proliferation and hematogenous
      dissemination of a tPMPs strain in experimental endocarditis, while the tPMPr
      phenotype confers a selective advantage associated with the enhanced progression
      of this infection.

PMID- 9632629
TI  - Inhibition of class II major histocompatibility complex antigen processing by
      Escherichia coli heat-labile enterotoxin requires an enzymatically active A
      subunit.
AB  - Escherichia coli heat-labile enterotoxin (LT) and cholera toxin (CT) were found
      to inhibit intracellular antigen processing. Processing was not inhibited by
      mutant LT with attenuated ADP-ribosyltransferase activity, CT B or LT B subunit,
      which enhanced presentation of preexisting cell surface peptide-class II major
      histocompatibility complex complexes. Inhibition of antigen processing correlated
      with A subunit ADP-ribosyltransferase activity.

PMID- 9632630
TI  - C2-domains, structure and function of a universal Ca2+-binding domain.

PMID- 9632631
TI  - Spontaneous and ligand-induced trafficking of CXC-chemokine receptor 4.
AB  - A chimeric protein consisting of CXC-chemokine receptor 4 (CXCR4) and the green
      fluorescent protein (GFP) was used for studying receptor localization and
      trafficking in real time in stably transduced HeLa, U-937, CEM, and NIH/3T3
      cells. CXCR4-GFP was fully active as a co-receptor in mediating human
      immunodeficiency virus (HIV) entry. Both CXCR4 and CXCR4-GFP were found to
      undergo significant spontaneous endocytosis. Only 51.5 +/- 7.8% of receptor
      molecules were found on the plasma membrane in CD4-positive cells, 43.9 +/- 8.5%
      were found in CD4-negative HeLa cells, 75.6 +/- 9.7% were found in U-937 cells,
      72.5 +/- 7.9 were found in CEM cells, and almost none were found in in NIH/3T3
      cells. Stromal cell-derived factor-1alpha induced rapid endocytosis of cell
      surface receptor molecules. A significant part of CXCR4 was targeted to lysosomes
      upon binding of the ligands, and recycling of internalized CXCR4 was not
      efficient. Only about 30% of receptor molecules recycled back to the cell surface
      in HeLa cells, 5% recycled in U937, and 10% recycled in CEM cells, suggesting
      that the protective effect of chemokines against HIV infection can be attributed
      not only to competition for binding but also to depletion of the co-receptor
      molecules from the cell surface. Envelope glycoprotein gp120 of syncytia
      inducing/lymphocyte tropic HIV-1 strains induced rapid internalization of CXCR4
      in both CD4-negative and CD4-positive cells, suggesting that gp120 is a high
      affinity ligand of CXCR4.

PMID- 9632632
TI  - Protein splicing in vitro with a semisynthetic two-component minimal intein.
AB  - Protein splicing elements, or inteins, catalyze their own excision from flanking
      polypeptide sequences, or exteins, thereby leading to the formation of new
      proteins in which the exteins are linked directly by a peptide bond. A trans
      splicing system, using separately purified and expressed N- and C-terminal intein
      fragments of about 100 amino acids each, fused to appropriate exteins, was
      recently derived from the Mycobacterium tuberculosis RecA intein (Mills, K. V.,
      Lew, B. M., Jiang, S.-Q., and Paulus, H. (1998) Proc. Natl. Acad. Sci. U. S. A.
      95, 3543-3548). We have replaced the C-terminal intein fragment of this system
      with synthetic peptides comprising 35-50 of the C-terminal residues of the RecA
      intein. The N-terminal intein fragment and the synthetic peptide were
      reconstituted by renaturation from guanidinium chloride. In the absence of added
      reductants, a disulfide-linked dimer of the N-terminal fragment and the peptide
      accumulated and could be induced to splice by reduction of its disulfide bond.
      The intermediate and spliced products were identified by polyacrylamide gel
      electrophoresis, mass spectrometry, and derivatization with thiol-reactive biotin
      followed by Western blotting with a streptavidin-enzyme conjugate. This is the
      first example of protein splicing involving a synthetic intein fragment and opens
      the way for studying the active site structure and function of the intein by the
      use of different synthetic peptides, including ones with non-natural amino acids.

PMID- 9632633
TI  - The tax oncoprotein of human T-cell leukemia virus type 1 associates with and
      persistently activates IkappaB kinases containing IKKalpha and IKKbeta.
AB  - The Tax oncoprotein of human T-cell leukemia virus type 1 (HTLV1) chronically
      activates transcription factor NF-kappaB by a mechanism involving degradation of
      IkappaBalpha, an NF-kappaB-associated cytoplasmic inhibitor. Tax-induced
      breakdown of IkappaBalpha requires phosphorylation of the inhibitor at Ser-32 and
      Ser-36, which is also a prerequisite for the transient activation of NF-kappaB in
      cytokine-treated T lymphocytes. However, it remained unclear how Tax interfaces
      with the cellular NF-kappaB/IkappaB signaling machinery to generate a chronic
      rather than a transient NF-kappaB response. We now demonstrate that Tax
      associates with cytokine-inducible IkappaB kinase (IKK) complexes containing
      catalytic subunits IKKalpha and IKKbeta, which mediate phosphorylation of
      IkappaBalpha at Ser-32 and Ser-36. Unlike their transiently activated
      counterparts in cytokine-treated cells, Tax-associated forms of IKK are
      constitutively active in either Tax transfectants or HTLV1-infected T
      lymphocytes. Moreover, point mutations in Tax that ablate its IKK-binding
      function also prevent Tax-mediated activation of IKK and NF-kappaB. Together,
      these findings suggest that the persistent activation of NF-kappaB in HTLV1
      infected T-cells is mediated by a direct Tax/IKK coupling mechanism.

PMID- 9632634
TI  - Identification of a novel domain of HIV tat involved in monocyte chemotaxis.
AB  - Human immunodeficiency virus (HIV) Tat is chemotactic for monocytes and dendritic
      cells, an activity that could play a key role in the expansion of HIV infection
      of accessory cells. To date, domains of Tat previously found to interact with
      cell surface molecules have shown only partial chemotactic activity toward
      monocytes. Using overlapping Tat peptides, we identify a novel region of Tat with
      a potent chemotactic activity for monocytes, reaching levels equal to Tat itself.
      This peptide also provokes monocyte polarization similar to Tat and is able to
      compete with Tat for induction of monocyte migration. Specific high affinity (kd
      = 3 x 10(-9) M) cell surface binding sites on monocyte cell surfaces for this
      region of Tat are demonstrated. These data indicate that the majority of Tat
      effects on monocytes are mediated by a novel region in the cysteine-rich and core
      domains. These domains are highly conserved among different HIV isolates,
      suggesting an important role in the establishment of HIV infection.

PMID- 9632635
TI  - The formation or the reduction of a disulfide bridge on the gamma subunit of
      chloroplast ATP synthase affects the inhibitory effect of the epsilon subunit.
AB  - We have studied the change of the catalytic activity of chimeric complexes that
      were formed by chloroplast coupling factor 1 (CF1) -gamma, alpha and beta
      subunits of thermophilic bacterial F1 after formation or reduction of the
      disulfide bridge of different gamma subunits modified by oligonucleotide-directed
      mutagenesis techniques. For this purpose, three mutant gamma subunits were
      produced: gamma Delta194-230, here 37 amino acids from Pro-194 to Ile-230 are
      deleted, gammaC199A, Cys-199 is changed to Ala, and gamma Delta200-204, amino
      acids from Asp-200 to Lys-204 are deleted. All of the chimeric subunit complexes
      produced from each of these mutant CF1-gamma subunits and alpha and beta subunits
      from thermophilic bacterial F1 lost the sensitivity against thiol reagents when
      compared with the complex containing wild-type CF1-gamma. The pH optimum (pH 8.5
      9.0) and the concentration of methanol to stimulate ATPase activities were not
      affected by these mutations. These indicate that the introduction of the
      mutations did not change the main features of ATPase activity of the chimeric
      complex. However, the interaction between gamma subunit and epsilon subunit was
      strongly influenced by the type of gamma subunit itself. Although the ATPase
      activity of the chimeric complex that contained gamma Delta200-204 or gammaC199A
      was inhibited by the addition of recombinant epsilon subunit from CF1 similarly
      to complexes containing the reduced wild-type gamma subunit, the recombinant
      epsilon subunit did not inhibit the ATPase of the complex, which contained the
      oxidized form of gamma subunit. Therefore the affinity of the epsilon subunit to
      the gamma subunit may be dependent on the state of the gamma subunit or the
      epsilon subunit may bind to the oxidized form of gamma subunit in a mode that
      does not inhibit the activity. The ATPase activity of the complex that contains
      gamma Delta194-230 was not efficiently inhibited by epsilon subunit. These
      results show that the formation or reduction of the disulfide bond on the gamma
      subunit may induce a conformational change in the region that directly affects
      the interaction of this subunit with the adjacent epsilon subunit.

PMID- 9632636
TI  - Grb10 identified as a potential regulator of growth hormone (GH) signaling by
      cloning of GH receptor target proteins.
AB  - The cloning of receptor targets procedure, used so far to identify proteins
      associated with tyrosine kinase receptors was modified to clone SH2 proteins able
      to bind to the growth hormone receptor (GHR). The cytoplasmic region of GHR, a
      member of the cytokine receptor superfamily does not contain tyrosine kinase
      activity. It was thus phosphorylated in bacteria by the Elk tyrosine kinase and
      radiolabeled to screen a mouse expression library. With this probe, we identified
      Shc and the p85 subunit of phosphatidylinositol 3-kinase as direct targets of the
      receptor. The other proteins identified, Csk, Shb, Grb4, and Grb10 are new
      potential transducers for cytokine receptors. We show in Huh-7 hepatoma cells
      that Grb10 and GHR associate under GH stimulation. Co-transfections in 293 cells
      further show that Grb10 interacts with both the GHR and Jak2. Functional tests
      demonstrate that Grb10 inhibits transcription of two reporter genes containing,
      respectively, the serum response element of c-fos and the GH response element 2
      of the Spi2.1 gene, whereas it has no effect on a reporter gene containing only
      Stat5 binding elements. Our results suggest that Grb10 is a new target for a
      member of the cytokine receptor family that down-regulates some GH signaling
      pathways downstream of Jak2 and independently of Stat5.

PMID- 9632637
TI  - E-box-binding repressor is down-regulated in hepatic stellate cells during up
      regulation of mannose 6-phosphate/insulin-like growth factor-II receptor
      expression in early hepatic fibrogenesis.
AB  - Hepatic stellate cells become activated during the early stages of hepatic injury
      associated with fibrogenesis. The mannose 6-phosphate/insulin-like growth factor
      II receptor (M6P/IGFIIR) plays an important role in early fibrogenesis by
      participating in the activation of latent transforming growth factor-beta, a
      potent inducer of the matrix proteins in activated stellate cells that define the
      fibrotic phenotype. In this study we examined hepatic stellate cell regulation of
      M6P/IGFIIR expression and found that M6P/IGFIIR mRNA transcript levels increased
      in stellate cells from rats exposed to carbon tetrachloride (CCl4), a potent
      fibrogenic stimulant. Two E-boxes residing in the proximal promoter of M6P/IGFIIR
      were found to each bind a novel 75-kDa transcription factor (P75) in quiescent
      stellate cells of normal livers. This E-box binding was down-regulated as an
      early response in stellate cells exposed to CCl4, coinciding with increased
      M6P/IGFIIR transcript levels. Mutagenized E-boxes in M6P/IGFIIR promoter
      chloramphenicol acetyltransferase (CAT) reporter constructs produced a
      substantial increase in reporter expression when compared with the corresponding
      native promoter-CAT construct when transfected in culture-activated stellate
      cells, suggesting P75's role as a repressor. The results indicate P75's
      participation in the regulation of M6P/IGFIIR transcription in hepatic stellate
      cells during fibrogenesis.

PMID- 9632638
TI  - Lactic acid efflux from white skeletal muscle is catalyzed by the monocarboxylate
      transporter isoform MCT3.
AB  - The newly cloned proton-linked monocarboxylate transporter MCT3 was shown by
      Western blotting and immunofluorescence confocal microscopy to be expressed in
      all muscle fibers. In contrast, MCT1 is expressed most abundantly in oxidative
      fibers but is almost totally absent in fast-twitch glycolytic fibers. Thus MCT3
      appears to be the major MCT isoform responsible for efflux of glycolytically
      derived lactic acid from white skeletal muscle. MCT3 is also expressed in several
      other tissues requiring rapid lactic acid efflux. The expression of both MCT3 and
      MCT1 was decreased by 40-60% 3 weeks after denervation of rat hind limb muscles,
      whereas chronic stimulation of the muscles for 7 days increased expression of
      MCT1 2-3-fold but had no effect on MCT3 expression. The kinetics and substrate
      and inhibitor specificities of monocarboxylate transport into cell lines
      expressing only MCT3 or MCT1 have been determined. Differences in the properties
      of MCT1 and MCT3 are relatively modest, suggesting that the significance of the
      two isoforms may be related to their regulation rather than their intrinsic
      properties.

PMID- 9632639
TI  - Four amino acid residues are critical for high affinity binding of neuromedin B
      to the neuromedin B receptor.
AB  - Three mammalian bombesin receptor subtypes have been characterized: the gastrin
      releasing peptide receptor (GRP-R), the neuromedin B receptor (NMB-R), and
      bombesin receptor subtype 3 (BRS-3). In a previous report we identified four
      amino acids that are critical for high affinity binding of bombesin and gastrin
      releasing peptide (GRP) to the GRP-R. These four amino acids are conserved in all
      species variants of the GRP-R and NMB-R which bind bombesin with high affinity,
      but they are diverged in BRS-3, the bombesin receptor subtype that binds bombesin
      with much lower affinity. Substituting these four divergent amino acids in BRS-3
      for the conserved amino acids in either GRP-R or NMB-R increased the affinity of
      the mutated BRS-3 (4DeltaBRS-3) for bombesin compared with wild-type BRS-3. We
      hypothesized that the same four amino acids might be critical for high affinity
      NMB binding to the NMB-R. In this study we confirm this hypothesis by showing
      that the affinity of NMB is increased in a mutant BRS-3 receptor (4DeltaBRS-3)
      that contains these four substitutions resulting in an affinity that is close to
      the affinity of wild-type NMB-R for NMB. In contrast, these four amino acid
      substitutions in BRS-3 did not result in the formation of a high affinity binding
      site for the recently described non-peptide NMB-R antagonist PD168368.

PMID- 9632640
TI  - The PR domain of the Rb-binding zinc finger protein RIZ1 is a protein binding
      interface and is related to the SET domain functioning in chromatin-mediated gene
      expression.
AB  - The PR domain, first noted as the PRDI-BF1-RIZ1 homologous region, defines a sub
      class of zinc finger genes that appear to function as negative regulators of
      tumorigenesis. This family includes the MDS1-EVI1 gene inactivated in myeloid
      leukemia, the PRDI-BF1/BLIMP1 transcription repressor of c-myc involved in
      driving B-cell differentiation, and the RIZ gene, which encodes proteins capable
      of binding to the retinoblastoma tumor suppressor protein (Rb). The PR domain of
      MDS1-EVI1 is disrupted by translocations linked to myeloid leukemia, resulting in
      the activation of the PR-minus oncogenic product EVI1. Remarkably similar to MDS1
      EVI1, RIZ gene also normally produces two protein products of different length,
      and the smaller protein RIZ2 lacks the PR domain of RIZ1 but is otherwise
      identical to RIZ1. These observations raise considerable interest to determine
      the function of PR. We show here that RIZ1 PR domain mediates protein-protein
      interaction. Recombinant fusion proteins of PR can bind to in vitro translated
      RIZ1 and RIZ2 proteins. The binding can be disrupted by amino acid substitutions
      at conserved residues of PR, suggesting that binding is specific. Of the three
      conserved exons of PR, the first two appear dispensable for binding, whereas the
      third exon is required. A region in the carboxyl terminus of RIZ proteins was
      mapped to be necessary and sufficient for PR binding. We also found that the PR
      domain shares significant sequence identity to the SET domain present in
      chromosomal proteins that function in modulating gene expression from yeast to
      mammals. Our data suggest that the PR domain is a derivative of SET domain and
      may function as protein binding interface in the regulation of chromatin-mediated
      gene expression.

PMID- 9632641
TI  - Unisite catalysis without rotation of the gamma-epsilon domain in Escherichia
      coli F1-ATPase.
AB  - Unisite [gamma-32P]ATP hydrolysis was studied in ECF1 from the mutant betaE381C
      after generating a single disulfide bond between beta and gamma subunits to
      prevent the rotation of the gamma/epsilon domain. The single beta-gamma cross
      link was obtained by removal of the delta subunit from F1 and then treating with
      CuCl2 as described previously (Aggeler, R., Haughton, M. A., and Capaldi, R. A.
      (1996) J. Biol. Chem. 270, 9185-9191). The mutant enzyme, betaE381C, had an
      increased overall rate of unisite hydrolysis of [gamma-32P]ATP compared with the
      wild type ECF1 due to increases in the rate of ATP binding (k+1), Pi release
      (k+3), and ADP release (k+4). Release of bound substrate ([gamma-32P]ATP) was
      also increased in the betaE381C mutant. Cross-linking between Cys-381 and the
      intrinsic Cys-87 of gamma caused a further increase in the rate of unisite
      catalysis, mainly by additional effects on nucleotide binding in the high
      affinity catalytic site (k+1 and k+4). In delta-subunit-free ECF1 from wild type
      or betaE381C F1, addition of an excess of ATP accelerated unisite catalysis.
      After cross-linking, unisite catalysis of betaE381C was not enhanced by the cold
      chase. The covalent linkage of gamma to beta increased the rate of unisite
      catalysis to that obtained by cold chase of ATP of the noncross-linked enzyme. It
      is concluded that the conversion of Glu-381 of beta to Cys induces an activated
      conformation of the high affinity catalytic site with low affinity for substrate
      and products. This state is stabilized by cross-linking the Cys at beta381 to Cys
      87 of gamma. We infer from the data that rotation of the gamma/epsilon rotor in
      ECF1 is not linked to unisite hydrolysis of ATP at the high affinity catalytic
      site but to ATP binding to a second or third catalytic site on the enzyme.

PMID- 9632642
TI  - Evidence of a functional interaction between serine 3 and serine 25 Mos
      phosphorylation sites. A dominant inhibitory role of serine 25 phosphorylation on
      Mos protein kinase.
AB  - Recently, we identified the major in vivo phosphorylation site on v-Mos as Ser
      56, which is phosphorylated by cyclic AMP dependent protein kinase (PKA). Others
      have shown that c-Mos phosphorylation at Ser-3 (equivalent to Ser-34 in v-Mos) is
      important for the interaction of c-Mos with its substrate MEK and for its
      stability and cytostatic factor activity in eggs. To investigate the role of Ser
      56 phosphorylation, we generated site-directed mutants of v-Mos that would mimic
      phosphorylation in terms of charge at positions 56 and 34. After mutating serine
      (S) residues with alanine (A) or glutamic acid (E) in different combinations,
      various v-Mos mutants were expressed in a rabbit reticulocyte lysate in vitro
      translation system and in COS-1 or NIH/3T3 cells. The effect of mutations on Mos
      function was evaluated by in vitro protein kinase assays and by the ability of
      Mos to cause neoplastic transformation of NIH/3T3 cells. The S56E but not the
      S56A mutation inhibited v-Mos kinase activity suggesting that Ser-56
      phosphorylation has an inhibitory role. As predicted from Xenopus c-Mos studies,
      S34A but not S34E mutation inhibited v-Mos activity. Studies with the double
      mutants showed that the S56E mutation but not S56A mutation inhibited v-Mos
      kinase activity of both S34A and S34E mutants. Interestingly, the S56A mutation
      blocked the inhibitory effect of the S34A mutation on v-Mos kinase suggesting
      that in c-Mos the corresponding serine (Ser-25) can influence the regulation of c
      Mos by Ser-3. Results showing inhibition of v-Mos kinase activity of the S34E
      mutant by the S56E mutation is significant as it suggests that doubly
      phosphorylated Mos at these residues would be inactive. Because residues
      corresponding to both v-Mos Ser-34 and Ser-56 are evolutionarily conserved in c
      Mos, the kinase activity of c-Mos during meiosis may also be regulated in the
      same manner as v-Mos kinase activity.

PMID- 9632643
TI  - Nucleotide-dependent tetramerization of CTP synthetase from Saccharomyces
      cerevisiae.
AB  - The nucleotide-dependent tetramerization of purified native URA7-encoded CTP
      synthetase (EC 6.3.4.2, UTP: ammonia ligase (ADP-forming)) from the yeast
      Saccharomyces cerevisiae was characterized. CTP synthetase existed as a dimer in
      the absence of ATP and UTP. In the presence of saturating concentrations of ATP
      and UTP, the CTP synthetase protein existed as a tetramer. Increasing
      concentrations of ATP and UTP caused a dose-dependent conversion of the dimeric
      species to a tetramer. The kinetics of enzyme tetramerization correlates with the
      kinetics of enzyme activity. The tetramerization of CTP synthetase was dependent
      on UTP and Mg2+ ions. ATP facilitated the UTP-dependent tetramerization of CTP
      synthetase by a mechanism that involved the ATP-dependent phosphorylation of UTP
      catalyzed by the enzyme. The glutaminase reaction that is catalyzed by the enzyme
      was not required for enzyme tetramerization. CTP, a potent inhibitor of CTP
      synthetase activity, did not inhibit the ATP/UTP-dependent tetramerization of the
      enzyme. Phosphorylation of the purified native CTP synthetase with protein kinase
      A and protein kinase C facilitated the nucleotide-dependent tetramerization.
      Dephosphorylation of native CTP synthetase with alkaline phosphatase prevented
      the nucleotide-dependent tetramerization of the enzyme. This correlated with the
      inactivation of CTP synthetase activity. Rephosphorylation of the
      dephosphorylated enzyme with protein kinase A and protein kinase C resulted in a
      partial restoration of the nucleotide-dependent tetramerization of the enzyme.
      This tetramerization correlated with the partial restoration of CTP synthetase
      activity. Taken together, these results indicated that enzyme tetramerization was
      required for CTP synthetase activity and that enzyme phosphorylation played an
      important role in the tetramerization and regulation of the enzyme.

PMID- 9632644
TI  - Purification, characterization, and cloning of a cytosolic aspartyl
      aminopeptidase.
AB  - An aminopeptidase with a preference for N-terminal aspartyl and glutamyl residues
      but distinct from glutamyl aminopeptidase (EC 3.4. 11.7) was purified to near
      homogeneity from rabbit brain cytosol. Its properties were similar to an enzyme
      described previously (Kelly, J. A., Neidle, E. L., and Neidle, A. (1983) J.
      Neurochem. 40, 1727-1734). Aspartyl aminopeptidase had barely detectable activity
      toward simple aminoacyl-naphthylamide substrates. Its activity was determined
      with the substrate Asp-Ala-Pro-naphthylamide in the presence of excess dipeptidyl
      peptidase IV (EC 3.4.14.5). The native enzyme has a molecular mass of 440 kDa and
      migrates as a single band of 55 kDa after SDS-polyacrylamide gel electrophoresis.
      The sequences of three tryptic peptides were used to screen the GenBankTM data
      base of expressed sequence tags. Human and mouse clones described as "similar to
      a yeast vacuolar aminopeptidase" and containing full-length cDNAs were identified
      and sequenced. The human cDNA was expressed in Escherichia coli. The amino acid
      sequence has significant homology to yeast aminopeptidase I, placing it as the
      first identified mammalian member of the M18 family of metalloproteinases.
      Homologous sequences in Caenorhabditis elegans and in prokaryotes revealed three
      conserved histidines, three conserved glutamates and five conserved aspartates.
      Aspartyl aminopeptidase is found at relatively high levels in all mammalian
      tissues examined and is likely to play an important role in intracellular protein
      and peptide metabolism.

PMID- 9632645
TI  - Cloning and functional characterization of a potential-sensitive, polyspecific
      organic cation transporter (OCT3) most abundantly expressed in placenta.
AB  - We have isolated a cDNA from rat placenta which, when expressed heterologously,
      mediates the transport of a wide spectrum of organic cations. The cDNA codes for
      a protein of 551 amino acids containing 12 putative transmembrane domains.
      Northern blot analysis indicates that this transporter is expressed most
      abundantly in the placenta and moderately in the intestine, heart, and brain. The
      expression is comparatively low in the kidney and lung and is undetectable in the
      liver. This transporter is distinct from the previously cloned organic cation
      transporters (OCT1, OCT2, NKT, NLT, RST, and OCTN1). When expressed in HeLa
      cells, the cDNA induces the transport of tetraethylammonium and guanidine.
      Competition experiments indicate that this transport process recognizes a large
      number of organic cations, including the neurotoxin 1-methyl-4-phenylpyridinium,
      as substrates. The cDNA-induced transport is markedly influenced by extracellular
      pH. However, when expressed in Xenopus laevis oocytes, the cDNA-induced transport
      is electrogenic, associated with the transfer of positive charge into the
      oocytes. Under voltage clamp conditions, tetraethylammonium evokes inward
      currents that are concentration- and potential-dependent. This potential
      sensitive organic cation transporter, designated as OCT3, represents a new member
      of the OCT gene family.

PMID- 9632646
TI  - Regulation of casein kinase I epsilon and casein kinase I delta by an in vivo
      futile phosphorylation cycle.
AB  - Casein kinase I delta (CKIdelta) and casein kinase I epsilon (CKIepsilon) have
      been implicated in the response to DNA damage, but the understanding of how these
      kinases are regulated remains incomplete. In vitro, these kinases rapidly
      autophosphorylate, predominantly on their carboxyl-terminal extensions, and this
      autophosphorylation markedly inhibits kinase activity (Cegielska, A., Gietzen, K.
      F., Rivers, A., and Virshup, D. M. (1998) J. Biol. Chem. 273, 1357-1364).
      However, we now report that while these kinases are able to autophosphorylate in
      vivo, they are actively maintained in the dephosphorylated, active state by
      cellular protein phosphatases. Treatment of cells with the cell-permeable
      serine/threonine phosphatase inhibitors okadaic acid or calyculin A leads to
      rapid increases in kinase intramolecular autophosphorylation. Since CKI
      autophosphorylation decreases kinase activity, this dynamic
      autophosphorylation/dephosphorylation cycle provides a mechanism for kinase
      regulation in vivo.

PMID- 9632647
TI  - Human monocyte-derived macrophages secrete two forms of proteoglycan-macrophage
      colony-stimulating factor that differ in their ability to bind low density
      lipoproteins.
AB  - This study evaluated whether human monocyte-derived macrophages synthesize
      specific types of proteoglycans with lipoprotein-binding capability that could
      contribute to lipid retention in the arterial wall. After labeling with either
      [35S]SO4 or [35S]methionine, macrophages secreted a high molecular mass
      proteoglycan, with glycosaminoglycan chains of approximately 18 kDa and core
      protein bands of approximately 100 and 55 kDa. Both core protein bands were
      recognized by an antibody to PG-100, an antibody that recognizes the proteoglycan
      form of macrophage colony-stimulating factor (PG-100/PG-MCSF). The interaction
      between PG-100/PG-MCSF and low density lipoproteins (LDL) was examined by gel
      mobility shift. In this system, PG-100/PG-MCSF was resolved further into two
      forms. The two forms had the same core proteins but differed in their overall
      size and glycosaminoglycan content. The larger form contained glycosaminoglycan
      chains that were entirely chondroitin ABC lyase-sensitive, whereas the smaller
      form contained chains that were sensitive to both chondroitin ABC lyase and
      heparinase. Both forms bound native LDL with high affinity, but the larger form
      bound LDL with higher affinity than the smaller form. The glycosaminoglycan
      chains of PG-100/PG-MCSF, but not the core proteins, were responsible for binding
      to native LDL. Mildly oxidized LDL and methyl-LDL, which have an electrophoretic
      charge similar to that of native LDL, also bound PG-100/PG-MCSF. In contrast,
      extensively oxidized LDL and acetyl-LDL, which are more electronegative than
      native LDL, did not bind to either form of PG-100/PG-MCSF. The demonstration of
      two forms of human monocyte-derived macrophage PG-100/PG-MCSF which bind LDL may
      represent an additional role for macrophages in the extracellular trapping of
      lipoproteins in atherosclerosis.

PMID- 9632648
TI  - Identification of cis-elements of the human endothelin-A receptor gene and
      inhibition of the gene expression by the decoy strategy.
AB  - Previously, we succeeded in molecular cloning of the cDNA and the gene for human
      endothelin-A receptor (ET-AR). In the present study, we define cis-elements in
      the 5'-flanking region of the ET-AR gene. Deletion analyses were performed in
      A7r5 cells, rat vascular smooth muscle cell line, and Chinese hamster ovary cells
      using ET-AR promoter-luciferase gene constructs including 5 kilobases of the 5'
      flanking region. These analyses demonstrated the existence of one negative
      regulatory element (-2.0 kilobases to -857 bases) and two positive regulatory
      elements (-137 to -53 and -53 to +251). Gel mobility shift assay revealed a
      nuclear protein binding to the region (-104 to -78) (R1). DNase I footprinting
      analysis showed a footprint spanning from -91 to -83 whose sequence is CCCCACCTT
      (ETA-P1). When a plasmid including R1 fragments (R1 decoy) was co-transfected
      into A7r5 cells with ET-AR (-137 to +251)-luciferase gene construct, it
      significantly reduced the luciferase activity in a dose-dependent manner.
      Moreover, R1 decoy down-regulated the endogenous ET-AR mRNA in A7r5 cells by a
      maximum of 75%. Thus, we identified cis-elements that regulate basal
      transcriptional activity of the ET-AR gene and proved the feasibility to suppress
      the expression of the ET-AR gene by the DNA decoy strategy using the positive
      regulatory element we identified.

PMID- 9632649
TI  - Ambiguities in mapping the active site of a conformationally dynamic enzyme by
      directed mutation. Role of dynamics in structure-function correlations in
      Escherichia coli adenylosuccinate synthetase.
AB  - On the basis of ligated crystal structures, Asn21, Asn38, Thr42, and Arg419 are
      not involved in the chemical mechanism of adenylosuccinate synthetase from
      Escherichia coli, yet these residues are well conserved across species. Purified
      mutants (Asp21 --> Ala, Asn38 --> Ala, Asn38 --> Asp, Asn38 --> Glu, Thr42 -->
      Ala, and Arg419 --> Leu) were studied by kinetics, circular dichroism
      spectroscopy, and equilibrium ultracentrifugation. Asp21 and Arg419 are not part
      of the active site, yet mutations at positions 21 and 419 lower kcat 20- and 10
      fold, respectively. Thr42 interacts only through its backbone amide with the
      guanine nucleotide, yet its mutation to alanine significantly increases Km for
      all substrates. Asn38 hydrogen-bonds directly to the 5'-phosphoryl group of IMP,
      yet its mutation to alanine and glutamate has no effect on Km values, but reduces
      kcat by 100-fold. The mutation Asn38 --> Asp causes 10-57-fold increases in Km
      for all substrates along with a 30-fold decrease in kcat. At pH 5.6, however, the
      Asn38 --> Asp mutant is more active, yet binds IMP 100-fold more weakly, than the
      wild-type enzyme. Proposed mechanisms of ligand-induced conformational change and
      subunit aggregation can account for the properties of mutant enzymes reported
      here. The results underscore the difficulty of using directed mutations alone as
      a means of mapping the active site of an enzyme.

PMID- 9632650
TI  - Cotranscription and intergenic splicing of human galactose-1-phosphate
      uridylyltransferase and interleukin-11 receptor alpha-chain genes generate a
      fusion mRNA in normal cells. Implication for the production of multidomain
      proteins during evolution.
AB  - In the past 10 years, much attention has been focused on transcription
      preinitiation complex formation as a target for regulating gene expression, and
      other targets such as transcription termination complex assemblage have been less
      intensively investigated. We established the existence of poly(A) site choice and
      fusion splicing of two adjacent genes, galactose-1-phosphate uridylyltransferase
      (GALT) and interleukin-11 receptor alpha-chain (IL-11Ralpha), in normal human
      cells. This 16-kilobase (kb) transcription unit contains two promoters (the first
      one is constitutive, and the second one, 8 kb downstream, is highly regulated)
      and two cleavage/polyadenylation signals separated by 12 kb. The promoter from
      the GALT gene yields two mRNAs, a 1.4-kb mRNA encoding GALT and a 3-kb fusion
      mRNA when the first poly(A) site is spliced out and the second poly(A) is used.
      The 3-kb mRNA codes for a fusion protein of unknown function, containing part of
      the GALT protein and the entire IL-11Ralpha protein. The GALT promoter/IL
      11Ralpha poly(A) transcript results from leaky termination and alternative
      splicing. This feature of RNA polymerase (pol) II transcription, which contrasts
      with efficient RNA pol I and pol III termination, may be involved, together with
      chromosome rearrangements, in the generation of fusion proteins with multiple
      domains and would have major evolutionary implications in terms of natural
      processes to generate novel proteins with common motifs. Our results, together
      with accumulation of genomic informations, will stimulate new considerations and
      experiments in gene expression studies.

PMID- 9632651
TI  - Purification and characterization of ryanodine receptor 3 from mammalian tissue.
AB  - The ryanodine receptors are intracellular Ca2+ release channels that play a key
      role in cell signaling via Ca2+. There are three isoforms. Isoform 1 from
      skeletal muscle and isoform 2 from heart have been characterized. Isoform 3 is
      widely distributed in many mammalian tissues although in minuscule amounts. Its
      low abundance has hampered its study. We now describe methodology to isolate
      mammalian isoform 3 in amounts sufficient for biochemical and biophysical
      characterization. Bovine diaphragm sarcoplasmic reticulum fractions enriched in
      terminal cisternae containing both isoforms 1 (>95%) and 3 (<5% of the ryanodine
      binding) served as starting source. Isoform 3 was selectively immunoprecipitated
      from the 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonic acid (CHAPS)
      solubilized fraction and eluted with peptide epitope. Isoform 3 thus prepared is
      highly purified as characterized by SDS-polyacryamide gel electrophoresis,
      Coomassie Blue staining, and by high affinity ryanodine binding. The purified
      isoform 3 was incorporated into planar lipid bilayers, and its channel properties
      were studied. Channel characteristics in common with the other two isoforms are
      slope conductance, higher selectivity to Ca2+ versus K+ (PCa/K approximately 6),
      and response to drugs and ligands. In its response to Ca2+ and ATP, it more
      closely resembles isoform 2. The first two-dimensional structure of isoform 3 was
      obtained by cryoelectron microscopy and image enhancement techniques.

PMID- 9632652
TI  - Clostridium difficile toxins A and B are cation-dependent UDP-glucose hydrolases
      with differing catalytic activities.
AB  - Toxins A and B of Clostridium difficile are UDP-glucose glucosyltransferases that
      exert their cellular toxicity primarily through their abilities to
      monoglucosylate, and thereby inactivate, Rho family small GTPases. Toxin A also
      hydrolyzes UDP-glucose, although this activity is not well characterized. In this
      study, we measured the kinetics of UDP-glucose hydrolysis by toxins A and B and
      found significant differences in the catalytic activities of these two
      structurally homologous toxins. The toxins displayed similar Michaelis constants
      (Km) for UDP-glucose, but the maximal velocity (Vmax) of toxin B was
      approximately 5-fold greater than that of toxin A. Toxins A and B exert their
      enzymatic actions intracellularly, and, interestingly, we found that each toxin
      absolutely required K+ for optimal hydrolase activity; Na+ was inactive. The
      toxins also required certain divalent cations for activity and exhibited a
      significantly greater Vmax and lower Km in the presence of Mn2+ as compared with
      Mg2+. We conclude that C. difficile toxins A and B are cation-dependent UDP
      glucose hydrolases that differ significantly in their catalytic activities, a
      finding that may have important implications in understanding their different
      cytotoxic effects.

PMID- 9632653
TI  - The basic domain in HIV-1 Tat protein as a target for polysulfonated heparin
      mimicking extracellular Tat antagonists.
AB  - Heparin binds extracellular HIV-1 Tat protein and modulates its HIV long terminal
      repeat (LTR)-transactivating activity (M. Rusnati, D. Coltrini, P. Oreste, G.
      Zoppetti, A. Albini, D. Noonan, F. d'Adda di Fagagna, M. Giacca, and M. Presta
      (1997) J. Biol. Chem. 272, 11313-11320). On this basis, the glutathione S
      transferase (GST)-TatR49/52/53/55/56/57A mutant, in which six arginine residues
      within the basic domain of Tat were mutagenized to alanine residues, was compared
      with GST-Tat for its capacity to bind immobilized heparin. Dissociation of the
      GST-TatR49/52/53/55/56/57A.heparin complex occurred at ionic strength
      significantly lower than that required to dissociate the GST-Tat.heparin complex.
      Accordingly, heparin binds immobilized GST-Tat and GST-TatR49/52/53/55/56/57A
      with a dissociation constant equal to 0.3 and 1.0 microM, respectively. Also, the
      synthetic basic domain Tat-(41-60) competes with GST-Tat for heparin binding.
      Suramin inhibits [3H]heparin/Tat interaction, 125I-GST-Tat internalization, and
      the LTR-transactivating activity of extracellular Tat in HL3T1 cells and prevents
      125I-GST-Tat binding and cell proliferation in Tat-overexpressing T53 cells. The
      suramin derivative 14C-PNU 145156E binds immobilized GST-Tat with a dissociation
      constant 5 times higher than heparin and is unable to bind GST
      TatR49/52/53/55/56/57A. Although heparin was an antagonist more potent than
      suramin, modifications of the backbone structure in selected suramin derivatives
      originated Tat antagonists whose potency was close to that shown by heparin. In
      conclusion, suramin derivatives bind the basic domain of Tat, prevent Tat/heparin
      and Tat/cell surface interactions, and inhibit the biological activity of
      extracellular Tat. Our data demonstrate that tailored polysulfonated compounds
      represent potent extracellular Tat inhibitors of possible therapeutic value.

PMID- 9632654
TI  - Distinct roles of two heme centers for transmembrane electron transfer in
      cytochrome b561 from bovine adrenal chromaffin vesicles as revealed by pulse
      radiolysis.
AB  - The reaction of monodehydroascorbate (MDA) radical with purified cytochrome b561
      from bovine adrenal chromaffin vesicles was investigated by the technique of
      pulse radiolysis. Radiolytically generated MDA radical oxidized rapidly the
      reduced form of cytochrome b561 to yield the oxidized form. Subsequently the
      oxidized form of cytochrome b561 was re-reduced by ascorbate in the medium. The
      second-order rate constants of the reaction of MDA radical were increased with
      decreasing pH, whereas a maximum of the second-order rate constant for the
      reaction with ascorbate was obtained around pH 6.8. At excess MDA radical to
      cytochrome b561 concentration, only half of the heme in cytochrome b561 was
      oxidized, indicating that only one of the two heme centers can react with MDA
      radical. On the other hand, when the reactions were examined using cytochrome
      b561 pretreated in a mild alkaline condition in the oxidized state, the
      cytochrome b561 could not be oxidized with MDA radical, suggesting that the heme
      center specific for the electron donation to MDA radical is selectively modified
      upon the alkaline treatment. These results suggest that the two heme b centers
      have distinct roles for the electron donation to MDA radical and the electron
      acceptance from ascorbate, respectively.

PMID- 9632655
TI  - Molecular cloning of the chicken oviduct ecto-ATP-diphosphohydrolase.
AB  - The chicken oviduct ecto-ATP diphosphohydrolase (ATPDase), a member of the ecto
      ATPase family, was purified to homogeneity previously (Strobel, R. S., Nagy, A.
      K., Knowles, A. F., Buegel, J., and Rosenberg, M. O. (1996) J. Biol. Chem. 271,
      16323-16331). It is an 80-kDa glycoprotein with high specific activity
      (approximately 1,000 micromol/min/mg with MgATP as the substrate) and hydrolyzes
      both nucleoside triphosphates and diphosphates. Using amino acid sequence
      information obtained from the purified enzyme, two partial cDNA clones were
      obtained using reverse transcriptase-polymerase chain reaction and library
      screening. This is the second ecto-ATPase family member and the first ecto
      ATPDase to be cloned from information derived from purified proteins. The deduced
      primary sequence of the chicken oviduct ecto-ATPDase indicates a protein of 493
      amino acid residues with a molecular mass of 54 kDa. The predicted orientation
      shows it to be anchored to the membrane by two transmembranous segments near the
      NH2 and COOH termini with very short intracytoplasmic peptides at either end. The
      bulk of the protein is extracellular and contains 12 potential N-glycosylation
      sites, several potential phosphorylation sites, and five sequences that are
      conserved in seven other related membrane proteins. Four of the conserved
      sequences, designated as apyrase conserved regions, are present in both ecto
      ATPases and soluble E-type ATPases. The fifth conserved region, which occurs near
      the COOH terminus of the eight proteins, is observed only in the membrane-bound
      ecto-ATPases. Unexpectedly, sequence comparison revealed that the chicken oviduct
      ecto-ATPDase is equally distant from the two ecto-ATPases, which exhibit low
      activity toward ADP, and the four putative ecto-ATPDases, which are closely
      related to CD39.

PMID- 9632656
TI  - Cooperative function of POU proteins and SOX proteins in glial cells.
AB  - Glial cells of the oligodendrocyte lineage express several highly related POU
      proteins including Tst-1/Oct6/SCIP and Brn-1. Tst-1/Oct6/SCIP, but not Brn-1
      efficiently cooperated with Sox10, the only SRY box protein so far identified in
      oligodendrocytes. Here we show that, in addition to Sox10, cells of the
      oligodendrocyte lineage contain significant amounts of the related SRY box
      proteins Sox4 and Sox11. During development, Sox11 was strongly expressed in the
      central nervous system. It was first detected in neural precursors throughout the
      neuroepithelium. During later stages of neural development, Sox11 was
      additionally expressed in areas of the brain in which neurons undergo
      differentiation. In agreement with its expression in neural precursors, Sox11
      levels in cells of the oligodendrocyte lineage were high in precursors and down
      regulated during terminal differentiation. Outside the nervous system, expression
      of Sox11 was also detected in the developing limbs, face, and kidneys. Structure
      function analysis revealed that Sox11 has a strong intrinsic transactivation
      capacity which is mediated by a transactivation domain in its carboxyl-terminal
      part. In addition, Sox11 efficiently synergized with Brn-1. Synergy was dependent
      on binding of both proteins to adjacent DNA elements, and required the presence
      of the respective transactivation domain in each protein. Our data suggest the
      existence of a specific code in which POU proteins require specific Sox proteins
      to exhibit cooperative effects in glial cells.

PMID- 9632657
TI  - Acrolein is a product of lipid peroxidation reaction. Formation of free acrolein
      and its conjugate with lysine residues in oxidized low density lipoproteins.
AB  - Lipoprotein peroxidation, especially the modification of apolipoprotein B-100,
      has been implicated to play an important role in the pathogenesis of
      atherosclerosis. However, there have been few detailed insights into the chemical
      mechanism of derivatization of apolipoproteins during oxidation. In the present
      study, we provide evidence that the formation of the toxic pollutant acrolein
      (CH2=CH-CHO) and its conjugate with lysine residues is involved in the oxidative
      modification of human low density lipoprotein (LDL). Upon incubation with LDL,
      acrolein preferentially reacted with lysine residues. To determine the structure
      of acrolein-lysine adduct in protein, the reaction of acrolein with a lysine
      derivative was carried out. Employing Nalpha-acetyllysine, we detected a single
      product, which was identified to be a novel acrolein-lysine adduct, Nalpha-acetyl
      Nepsilon-(3-formyl-3,4-dehydropiperidino )lysine. The acid hydrolysis of the
      adduct led to the derivative that was detectable with amino acid analysis. It was
      revealed that, upon in vitro incubation of LDL with acrolein, the lysine residues
      that had disappeared were partially recovered by Nepsilon-(3-formyl-3, 4
      dehydropiperidino)lysine. In addition, we found that the same derivative was
      detected in the oxidatively modified LDL with Cu2+ and that the adduct formation
      was correlated with LDL peroxidation assessed by the consumption of alpha
      tocopherol and cholesteryl ester and the concomitant formation of cholesteryl
      ester hydroperoxide. Enzyme-linked immunosorbent assay that measures free
      acrolein revealed that a considerable amount of acrolein was released from the
      Cu2+-oxidized LDL. Furthermore, metal-catalyzed oxidation of arachidonate was
      associated with the formation of acrolein, indicating that polyunsaturated fatty
      acids including arachidonate represent potential sources of acrolein generated
      during the peroxidation of LDL. These results indicate that acrolein is not just
      a pollutant but also a lipid peroxidation product that could be ubiquitously
      generated in biological systems.

PMID- 9632658
TI  - Novel recombinant analogues of bovine placental lactogen. G133K and G133R provide
      a tool to understand the difference between the action of prolactin and growth
      hormone receptors.
AB  - Two new analogues of bovine placental lactogen (bPL), bPL(G133K) and bPL(G133R),
      were expressed in Escherichia coli, refolded, and purified to a native form.
      Binding experiments, which are likely to represent the binding to site 1 only, to
      intact FDC-P1 cells transfected with rabbit (rb) growth hormone receptor (GHR) or
      with human (h) GHR, to Nb2 rat lymphoma cells, or to rabbit mammary gland
      membranes prolactin receptor (PRLR), revealed only small or no reduction in
      binding capacity. The complex formation between these analogues and receptor
      extracellular domains (R-ECD) of various hormones was determined by gel
      filtration. Wild type bPL yielded 1:2 complex with hGHR-ECD, rat PRLR-ECD, and
      rbPRLR-ECD, whereas both analogues formed only 1:1 complexes with all R-ECDs
      tested. Real time kinetics experiments demonstrated that the ability of the
      analogues to form homodimeric complexes was compromised in both PRLR- and GHR
      ECDs. The biological activity transduced through lactogenic receptors in in vitro
      bioassays in rabbit mammary gland acini culture and in Nb2 cells was almost fully
      retained, whereas the activity transduced through somatogenic receptors in FDC-P1
      cells transfected with rbGHRs or with hGHRs was abolished. Both analogues
      exhibited antagonistic activity in the latter cells. To explain the discrepancy
      between the effect of the mutation on the signal transduced by PLR versus GHRs we
      suggest that: 1) the mutation impairs the ability of site 2 of bPL to form a
      stable homodimeric complex with both lactogenic and somatogenic receptors by a
      drastic shortening of the half-life of 2:1 complex; 2) the transient existence of
      the homodimeric complex is still sufficient to initiate the signal transduced
      through lactogenic receptors but not through somatogenic receptors; and 3) one
      possible reason for this difference is that JAK2, which serves as a mediator of
      both receptors, is already associated with lactogenic receptors prior to hormone
      binding-induced receptor dimerization, whereas in somatogenic receptors the JAK2
      receptor association occurs subsequently to receptor dimerization.

PMID- 9632659
TI  - Identification of the minimal requirements for binding to the human epidermal
      growth factor (EGF) receptor using chimeras of human EGF and an EGF repeat of
      Drosophila Notch.
AB  - Many proteins contain so-called epidermal growth factor (EGF)-like domains that
      share the characteristic spacing of cysteines and glycines with members of the
      EGF family. They are, however, functionally unrelated, despite the fact that the
      three-dimensional structure of these EGF-like domains, also, is often very
      similar to that of the EGF receptor agonists. In the present study, we linked an
      EGF-like repeat from the Drosophila Notch protein to the N- and C-terminal linear
      tail sequences of human EGF (hEGF), and we showed that this chimera (E1N6E) is
      unable to bind or activate the hEGF receptor. This recombinant protein was then
      used as a basic construct for identifying the minimal requirements for high
      affinity EGF receptor binding and activation. We selectively reintroduced a
      limited number of important hEGF-derived residues, and by using this unique
      approach, we were able to make hEGF/Notch chimeras that, compared with wild type
      hEGF, showed nearly 100% binding affinity and mitogenic activity on HER-14 cells
      expressing the hEGF receptor.

PMID- 9632660
TI  - An oligonucleotide inhibits oligomerization of a rolling circle initiator protein
      at the pT181 origin of replication.
AB  - A large number of plasmids have been shown to replicate by a rolling circle (RC)
      mechanism. The initiators encoded by these plasmids have origin-specific, nicking
      closing activity that is required for the initiation and termination of RC
      replication. Since the initiators of many RC plasmids are rate-limiting for
      replication, these proteins are usually inactivated after supporting one round of
      replication. In the case of the pT181 plasmid, inactivation of the initiator RepC
      protein occurs by the attachment of an oligonucleotide to its active tyrosine
      residue. We have generated the inactivated form of RepC, termed RepC*, in vitro
      and investigated the effects of attachment of the oligonucleotide on its various
      biochemical activities. Our results demonstrate that while RepC* is inactive in
      nicking-closing and replication activities due to the blockage of its active
      tyrosine residue, it is competent in origin DNA binding and DNA religation
      activities. We have investigated the oligomeric state of RepC and RepC* and found
      that RepC exists as a dimer in solution and can oligomerize on the DNA. We have
      generated heterodimers in vitro between the wild-type and epitope-tagged RepC
      proteins. In electrophoretic mobility shift experiments, the initiator
      heterodimers generated a novel DNA-protein complex, demonstrating that it binds
      to DNA as a dimer. We have shown that a DNA binding mutant of RepC can be
      targeted to the origin in the presence of the wild-type protein primarily through
      a protein-protein interaction. Interestingly, RepC* is defective in its ability
      to oligomerize on the DNA. RepC* inhibited the DNA binding and replication
      activity of wild-type RepC to only a very limited extent, suggesting that it may
      play only a minor regulatory role in replication in vivo. Based on these and
      earlier results, we propose a model for the role of RepC during the initiation
      and termination of pT181 RC replication.

PMID- 9632661
TI  - Sequence-specific changes in the metal site of ferric bleomycin induced by the
      binding of DNA.
AB  - The binding of the iron complex of the antineoplastic glycopeptide bleomycin A2
      (Fe-BLM) to calf thymus DNA and the self-complementary oligonucleotides d(CGCGCG)
      and d(ATATAT) has been studied using optical, EPR, and resonance Raman
      spectroscopies. An increase in the intensity of the bands at 365 and 384 nm is
      observed in the optical spectrum of Fe(III)-BLM when the drug binds to either
      oligonucleotide. However, in the presence of phosphate, this increase is observed
      only with d(CGCGCG) and not with d(ATATAT). In addition, the gmax feature in the
      EPR spectrum of low spin Fe(III)-BLM is narrowed in a way suggesting a reduction
      of possible conformers that the drug can achieve when it is bound to d(CGCGCG) or
      to calf thymus DNA but not when bound to d(ATATAT). When Fe(III)-BLM is bound to
      d(CGCGCG), changes in the resonance Raman spectrum of the metal drug complex
      suggest conformational changes in three of the ligands to iron: the beta
      hydroxyhistidyl amide, the pyrimidine, and the axial hydroxide. In addition, the
      Fe-OH band undergoes narrowing, again consistent, with the reduction of
      conformers of the drug. No such resonance Raman changes are observed upon binding
      to d(ATATAT). The changes in the pyrimidine modes upon binding d(CGCGCG) to the
      drug are consistent with a recently proposed model (Wu, W., Vanderwall, D. E.,
      Turner, C. J., Kozarich, J. W., and Stubbe, J. (1996) J. Am. Chem. Soc. 118, 1281
      1294) of DNA recognition by activated bleomycin, HOO-Fe(III)-BLM, in which the
      pyrimidine moiety of the drug is important for the preferential cleavage of 5'
      GpPy-3' sequences.

PMID- 9632662
TI  - TIMP-2 promotes activation of progelatinase A by membrane-type 1 matrix
      metalloproteinase immobilized on agarose beads.
AB  - Membrane-type 1 matrix metalloproteinase (MT1-MMP)/MMP-14 is the activator of
      progelatinase A (proGelA)/proMMP-2 on the cell surface. However, it was a paradox
      that a tissue inhibitor of metalloproteinase-2 (TIMP-2), which is an inhibitor of
      MT1-MMP, is required for proGelA activation by the cells expressing MT1-MMP. In
      this study, a truncated MT1-MMP having a FLAG-tag sequence at the C terminus (MT1
      F) was immobilized onto agarose beads (MT1-F/B) and used to analyze the role of
      TIMP-2. The proteolytic activity of MT1-F/B against a synthetic peptide substrate
      was inhibited by TIMP-2 in a dose-dependent manner. In contrast, TIMP-2 promoted
      the processing of proGelA by MT1-F/B at low concentrations and inhibited it at
      higher concentrations. TIMP-2 promoted the binding of proGelA to the MT1-F on the
      beads by forming a trimolecular complex, which was followed by processing of
      proGelA. A stimulatory effect of TIMP-2 was observed under conditions in which
      unoccupied MT1-F was still available. Thus, the ternary complex is thought to act
      as a means to concentrate the substrate to the bead surface and to present it to
      the neighboring free MT1-F.

PMID- 9632663
TI  - Characterization of the human transcobalamin II promoter. A proximal GC/GT box is
      a dominant negative element.
AB  - Deletion and mutagenesis of the 5'-flanking region of the human transcobalamin II
      (TC II) transfected in human intestinal epithelial Caco-2 cells have revealed
      that TC II promoter activity is: (a) very weak; (b) restricted to a core region (
      29 to -163) that contained multiple transcription initiation sites; (c) not
      dependent on other potential elements, such as a distally localized CCAAT box, a
      CF1, a HIP1 binding motif and a MED-1 element; (d) modulated weakly by a positive
      acting GC box (-568-GAGGCGGTGC) and strongly by a proximal GC/GT overlapping box
      (-179 CCCCCGCCCCACCCC). Gel shift and immunosupershift analyses demonstrated that
      both the positive-acting GC box and the negative-acting GC/GT box were recognized
      by Sp1 and Sp3. Co-transfection studies using Sp1 and/or Sp3 expression plasmids
      revealed that while Sp1 stimulated, Sp3 repressed Sp1-mediated transactivation of
      TC II transcription. The proximal GC/GT box also acted as a negative element in
      human chronic myelogenous leukemia K-562 and HeLa cells. These results suggest
      that tissue/cell specific expression of the TC II gene may be controlled by the
      relative ratios of Sp1 and Sp3 that bind to the GC/GT box and the weak promoter
      activity of TC II is due to the transcriptional repression caused by the binding
      of Sp3 to the proximal GC/GT box.

PMID- 9632664
TI  - HLH106, a Drosophila sterol regulatory element-binding protein in a natural
      cholesterol auxotroph.
AB  - In mammalian cells, sterol regulatory element-binding proteins (SREBPs)
      coordinate metabolic flux through the cholesterol and fatty acid biosynthetic
      pathways in response to intracellular cholesterol levels. We describe experiments
      that evaluate the functional equivalence of mammalian SREBPs and the insect
      homologue of SREBP-1a, HLH106, in both mammalian and insect cell culture systems.
      HLH106 binds to both palindromic E-boxes and direct repeat sterol regulatory
      elements (SREs) efficiently, suggesting that it has a dual DNA binding
      specificity similar to the mammalian proteins. The amino-terminal "mature"
      protein activates transcription from mammalian SREs in both mammalian and
      Drosophila tissue culture cells. Additionally, HLH106 also requires a ubiquitous
      regulatory co-activator to efficiently activate transcription from mammalian
      SREs. These properties are shared with its mammalian counterparts. When expressed
      in mammalian cells, the carboxyl-terminal portion also localizes to perinuclear
      membranes similar to mammalian SREBPs. Furthermore, membrane-bound HLH106 is
      proteolytically processed in response to intracellular sterol levels in mammalian
      cells in an SREBP cleavage-activating protein-stimulated fashion. The presence of
      an SREBP homologue in Drosophila whose processing is regulated by intracellular
      sterol levels when expressed in mammalian cells suggests that related processing
      machinery exists in insect cells. This is notable, since insects are reportedly
      incapable of de novo sterol biosynthesis.

PMID- 9632665
TI  - Isolation and characterization of monomeric and dimeric CP47-reaction center
      photosystem II complexes.
AB  - Using the detergents n-dodecyl beta-D-maltoside and heptyl thioglycopyranoside, a
      subcore complex of photosystem II (PSII) has been isolated that contains the
      chlorophyll-binding protein, CP47, and the reaction center components, D1, D2,
      and cytochrome b559. We have found, by using sucrose density centrifugation, that
      the resulting preparation consisted of a mixture of dimeric and monomeric forms
      of the CP47 reaction center (RC) complex, having molecular masses of 410 +/- 30
      and 200 +/- 28 kDa, respectively, as estimated by size exclusion chromatography.
      The level of the dimer in the preparation is significantly higher than the
      monomeric form. Both the monomer and dimer contain the proteins CP47, D1, and D2
      and the alpha- and beta-subunits of cytochrome b559. Analyses by mass
      spectrometry and N-terminal sequencing showed that both forms of the CP47-RC
      complex contain the products of the psbI, psbTc (chloroplast gene), and psbW with
      molecular masses of 4195.5, 3849.6, and 5927.4 Da, respectively. In contrast to
      the monomeric form, the CP47-RC dimer contained two extra proteins with low
      molecular weights, identified as the products of the psbL and psbK genes having
      molecular masses of 4365.5 and 4292.1, respectively. It was also found that the
      dimer contained slightly more molecules of chlorophyll a (21 +/- 2.5) than the
      monomer (18 +/- 1.5), a characteristic also observed in the room temperature
      absorption spectrum by comparing the ratio of absorption at 416 and 435 nm. Of
      particular note was the finding that the dimer, but not the monomer, contained
      plastoquinone-9 (estimated to be 1.5 +/- 0.3 molecules per RC). The results
      indicate that the CP47-RC monomer is derived from the dimeric form of the
      complex, and therefore the latter is likely to represent an in vivo conformation.
      The PsbTc as well as the PsbI and PsbW proteins are identified as being
      intimately associated with the D1 and D2 proteins, and in the case of the dimer,
      importance is placed on the PsbL and PsbK proteins in sustaining plastoquinone
      binding and maintenance of the dimeric organization. Assuming only one copy of
      the alpha- and beta-subunits of cytochrome b559, the monomeric and dimeric forms
      of the complex would be expected to contain 21 and 23 x 2 transmembrane helices,
      respectively.

PMID- 9632666
TI  - Comparison of the functional properties of the monomeric and dimeric forms of the
      isolated CP47-reaction center complex.
AB  - Chlorophyll fluorescence, thermoluminescence, and EPR spectroscopy have been used
      to investigate the functional properties of the monomeric and dimeric forms of
      the photosystem II CP47-reaction center (CP47-RC) subcore complex that was
      isolated (Zheleva, D., Sharma, J., Panico, M., Morris, H. R., and Barber, J.
      (1998) J. Biol. Chem. 273, 16122-16127). Chlorophyll fluorescence yield changes
      induced either by the initiation of continuous actinic light or by repetitive
      light flashes indicated that the dimeric, but not the monomeric, form of the CP47
      RC complex showed secondary electron transport properties indicative of QA
      reduction. Thermoluminescence measurements also clearly distinguished the monomer
      from the dimer in that the latter showed a ZV band, which appeared at -55
      degreesC, following illumination at -80 degreesC. This band has been determined
      to be an indicator of the photoaccumulation of QA-. The ability of the dimeric
      CP47-RC to show secondary electron transport properties was clearly demonstrated
      by EPR studies. The dimer was characterized by organic radical signals at about g
      = 2 induced either by illumination or by the addition of dithionite. The
      dithionite-induced signal was attributed to QA-, but there was no indication of
      any interaction with non-heme iron. The signal induced by light was more complex,
      being composed not only of the QA- radical but also of radicals generated on the
      donor side. Difference analyses indicated that one of these radicals is likely to
      be due to a D1 tyrosine 161 or D2 tyrosine 161. In contrast, the monomeric CP47
      RC complex did not show similar EPR-detectable radicals and instead was dominated
      by a high yield of the spin-polarized triplet signal generated by recombination
      reactions between the oxidized primary reductant, pheophytin, and the primary
      donor, P680. It is also concluded from EPR analyses that both the monomeric and
      dimeric forms of the CP47-RC subcore complex contain one cytochrome b559 per
      reaction center. Overall the results suggest that photosystem II normally
      functions as a dimer complex and that monomerization at the level of the CP47-RC
      subcore complex leads to destabilization of the bound plastoquinone, which
      functions as QA.

PMID- 9632667
TI  - Functional consequences of monoglucosylation of Ha-Ras at effector domain amino
      acid threonine 35.
AB  - Monoglucosylation of low molecular mass GTPases is an important post
      translational modification by which microbes interfere with eukaryotic cell
      signaling. Ha-Ras is monoglucosylated at effector domain amino acid threonine 35
      by Clostridium sordellii lethal toxin, resulting in a blockade of the downstream
      mitogen-activated protein kinase cascade. To understand the molecular
      consequences of this modification, effects of glucosylation on each step of the
      GTPase cycle of Ras were analyzed. Whereas nucleotide binding was not
      significantly altered, intrinsic GTPase activity was markedly decreased, and
      GTPase stimulation by the GTPase-activating protein p120(GAP) and neurofibromin
      NF-1 was completely blocked, caused by failure to bind to glucosylated Ras.
      Guanine nucleotide exchange factor (Cdc25)-catalyzed GTP loading was decreased,
      but not completely inhibited. A dominant-negative property of modified Ras to
      sequester exchange factor was not detectable. However, the crucial step in
      downstream signaling, Ras-effector coupling, was completely blocked. The Kd for
      the interaction between Ras.GTP and the Ras-binding domain of Raf was 15 nM,
      whereas glucosylation increased the Kd to >1 mM. Because the affinity of Ras.GDP
      for Raf (Kd = 22 microM) is too low to allow functional interaction, a glucose
      moiety at threonine 35 of Ras seems to block completely the interaction with Raf.
      The net effect of lethal toxin-catalyzed glucosylation of Ras is the complete
      blockade of Ras downstream signaling.

PMID- 9632668
TI  - The C-terminal region of the factor V B-domain is crucial for the anticoagulant
      activity of factor V.
AB  - Factor V (FV) is recently shown to express anticoagulant activity. It functions
      as a synergistic cofactor with protein S to activated protein C (APC) in the
      degradation of factor VIIIa (FVIIIa). FV is composed of multiple domains, A1-A2-B
      A3-C1-C2. Thrombin cleaves FV at Arg-709, Arg-1018, and Arg-1545 that leads to
      the generation of a procoagulant FV species which functions as a cofactor to
      factor Xa (FXa) in the activation of prothrombin to thrombin. During the
      activation process, the B-domain is released from the heavy (A1-A2) and light
      chains (A3-C1-C2) which constitute the active FV (FVa). To elucidate which effect
      the different thrombin cleavages in FV have on the ability of FV to express APC
      cofactor activity, seven recombinant FV mutants containing all possible
      combinations of mutated and native thrombin cleavage sites were tested in a
      FVIIIa degradation assay. Thrombin cleavage at Arg-709 and/or Arg-1018 yielded FV
      molecules that were still able to function as APC cofactors, whereas cleavage at
      Arg-1545 led to a complete loss in APC-cofactor function. This suggests that the
      APC-cofactor function of FV depends on the B-domain remaining attached to the A3
      domain. The importance of the FV B-domain for expression of APC-cofactor activity
      was further investigated using two B-domain deleted FV molecules, FV des-709-1545
      (with the whole B-domain deleted) and FV des-709-1476 (with amino acids 710-1476
      of the B-domain being removed). FV des-709-1476 expressed APC-cofactor activity,
      whereas the FV des-709-1545 was completely devoid of such activity. Thus, the C
      terminal part of the B-domain (residues 1477-1545) was crucial for the APC
      cofactor function. FV and factor VIII (FVIII) are homologous proteins having
      similar domain organization. A FV/FVIII chimera, harboring the B-domain from
      FVIII (FVBVIII) instead of the FV B-domain did not work as an APC cofactor,
      further illustrating the importance of the FV B-domain for the APC-cofactor
      function.

PMID- 9632669
TI  - Molecular or pharmacologic perturbation of the link between glucose and lipid
      metabolism is without effect on glucose-stimulated insulin secretion. A re
      evaluation of the long-chain acyl-CoA hypothesis.
AB  - The mechanism by which glucose stimulates insulin secretion from the pancreatic
      islets of Langerhans is incompletely understood. It has been suggested that
      malonyl-CoA plays a regulatory role by inhibiting fatty acid oxidation and
      promoting accumulation of cytosolic long-chain acyl-CoA (LC-CoA). In the current
      study, we have re-evaluated this "long-chain acyl-CoA hypothesis" by using
      molecular and pharmacologic methods to perturb lipid metabolism in INS-1
      insulinoma cells or rat islets during glucose stimulation. First, we constructed
      a recombinant adenovirus containing the cDNA encoding malonyl-CoA decarboxylase
      (AdCMV-MCD), an enzyme that decarboxylates malonyl-CoA to acetyl-CoA. INS-1 cells
      treated with AdCMV-MCD had dramatically lowered intracellular malonyl CoA levels
      compared with AdCMV-betaGal-treated cells at both 3 and 20 mM glucose. Further,
      at 20 mM glucose, AdCMV-MCD-treated cells were less effective at suppressing [1
      14C]palmitate oxidation and incorporated 43% less labeled palmitate and 50% less
      labeled glucose into cellular lipids than either AdCMV-betaGAL-treated or
      untreated INS-1 cells. Despite the large metabolic changes caused by expression
      of MCD, insulin secretion in response to glucose was unaltered relative to
      controls. The alternative, pharmacologic approach for perturbing lipid metabolism
      was to use triacsin C to inhibit long-chain acyl-CoA synthetase. This agent
      caused potent attenuation of palmitate oxidation and glucose or palmitate
      incorporation into cellular lipids and also caused a 47% decrease in total LC
      CoA. Despite this, the drug had no effect on glucose-stimulated insulin secretion
      in islets or INS-1 cells. We conclude that significant disruption of the link
      between glucose and lipid metabolism does not impair glucose-stimulated insulin
      secretion in pancreatic islets or INS-1 cells.

PMID- 9632670
TI  - Nuclear receptor involvement in the regulation of rat cytochrome P450 3A23
      expression.
AB  - Many genes of the cytochrome P450 3A (CYP3A) subfamily, including several human
      and rat isoforms, are inducible by glucocorticoids. In the rat CYP3A23 gene, a
      110-base pair segment of the proximal 5'-flanking region mediates dexamethasone
      activation. Three binding sites (DexRE-1, DexRE-2, and Site A), identified by
      DNase I footprinting analysis, were characterized for their relative contribution
      to both basal activity and dexamethasone inducibility. Site-directed mutagenesis
      of DexRE-1 (-144 to -169) and DexRE-2 (-118 to -136) demonstrated that each
      contained a core imperfect AGGTCA direct repeat, which comprised a consensus
      nuclear receptor binding site, and was essential for dexamethasone responsiveness
      but was not required for basal activity. Competition gel shift and supershift
      analyses revealed that both sites can bind the orphan nuclear receptor chicken
      ovalbumin upstream promoter-transcription factor. Site A (-85 to -110) was shown
      to be important for both basal activity and dexamethasone responsiveness. Point
      mutants displayed a reduced (2-3-fold) induction response, compared with 15-fold
      for wild-type, which was accompanied by a 40-60% drop in basal activity. Site A
      was shown to bind the liver-enriched nuclear receptor hepatocyte nuclear factor
      4. Our studies demonstrate that the mechanism mediating glucocorticoid-inducible
      transcriptional activity of CYP3A23 involves multiple binding sites for members
      of the nuclear receptor superfamily.

PMID- 9632671
TI  - Brefeldin A (BFA) inhibits basolateral membrane (BLM) delivery and dimerization
      of transcobalamin II receptor in human intestinal epithelial Caco-2 cells. BFA
      effects on BLM cholesterol content.
AB  - Brefeldin A (BFA) treatment of Caco-2 cells (5 microg/ml for 12 h) reduced by 90%
      the cholesterol, but not the phospholipid (PL), levels of the basolateral
      membrane (BLM), thus altering its PL/cholesterol molar ratio from 2.6 to 22.0,
      and decreasing its steady state fluorescent anisotropy (rs) from 0.27 to 0.15.
      BFA treatment for 12 h also resulted in complete loss of transcobalamin II
      receptor (TC II-R) activity/protein levels in the BLM and the disappearance of
      trans-Golgi network (TGN) morphology as revealed by confocal immunofluorescence
      microscopy using antibody to TGN 38. However, BFA treatment had no effect on
      either total cellular cholesterol, TC II-R activity, or PL levels. When cells
      treated with BFA for 12 h were exposed to BFA-free medium for 0-24 h, all of the
      effects were reversed, including reappearance of normal TGN morphology. TC II-R
      delivered to the BLM during this period was progressively sialylated and changed
      its physical state from a monomer (8 h) to a dimer (12 h), coinciding with
      increased delivery (11-53 pmol) of cholesterol to the BLM and an increase in the
      BLM rs from 0.15 to 0.21. These results indicate that cholesterol, but not PL,
      delivery to the BLM of Caco-2 cells is BFA-sensitive, and cholesterol, by
      influencing the higher order of the BLM, is essential for TC II-R dimerization.

PMID- 9632672
TI  - Exon sequence is required for regulated RNA splicing of the human fibroblast
      growth factor receptor-1 alpha-exon.
AB  - Alternative RNA processing of the human fibroblast growth factor receptor-1
      transcript results in receptor forms that vary in their affinity for fibroblast
      growth factor. An alternative RNA processing event involving recognition of the
      alpha-exon is deregulated during neoplastic transformation of glial cells. We
      have previously established a splicing reporter/transfection cell culture model
      system to identify sequences involved in recognition of this exon. In this study,
      the system was used to identify two sequence elements that differentially
      function to regulate splicing of this exon. Exclusion of the alpha-exon in
      glioblastoma cells specifically required the downstream intron sequence
      comprising the 5'-splice site. Replacement or mutation of this sequence
      increasing complementarity to U1 RNA resulted in enhanced exon recognition in SNB
      19 glioblastoma cells. Sequences within the exon were found to be required for
      alpha-exon inclusion. Deletion and gain-of-function experiments identified a 69
      nucleotide exon sequence that was specifically required for alpha-exon inclusion.
      These studies indicate that multiple sequences are required for the regulated
      recognition of the alpha-exon.

PMID- 9632673
TI  - Different requirements for signal transducer and activator of transcription
      1alpha and interferon regulatory factor 1 in the regulation of low molecular mass
      polypeptide 2 and transporter associated with antigen processing 1 gene
      expression.
AB  - The components of the antigen processing machinery, low molecular mass
      polypeptide (LMP) 2 and transporter associated with antigen processing (TAP) 1,
      are encoded by closely linked genes within the major histocompatibility complex
      class II subregion. Although the two genes share a bi-directional promoter, LMP2
      and TAP1 have differential cellular expression. TAP1 is expressed constitutively.
      However, LMP2 expression requires induction by interferon-gamma in most cells.
      The regulatory elements within the LMP2/TAP1 promoter and the transcription
      factors that bind these elements have been defined. However, how these
      transactivators regulate differential TAP1 and LMP2 gene transcription is not
      known. We have addressed this question by analyzing three human melanoma cell
      lines with distinct phenotypes of LMP2 and TAP1 expression. Whereas binding of
      either interferon regulatory factor 1 or Stat1 to the overlapping interferon
      consensus sequence-2/GAS is sufficient for regulating transcription of the TAP1
      gene, binding of both factors is required for LMP2 gene transcription. This
      conclusion is supported by restoration of LMP2 gene transcription following
      transfection of wild type Stat1alpha or interferon regulatory factor 1 cDNA into
      cells lacking these transcription factors. The flexibility in the regulation of
      the TAP1 gene may reflect its role in maintaining immune surveillance.
      Furthermore, lack of LMP2 gene transcription in quiescent human cells suggests
      that LMP2 expression reflects a state of cell activation.

PMID- 9632674
TI  - Identification of glutathione as a driving force and leukotriene C4 as a
      substrate for oatp1, the hepatic sinusoidal organic solute transporter.
AB  - oatp1 is an hepatic sinusoidal organic anion transporter that mediates uptake of
      various structurally unrelated organic compounds from blood. The driving force
      for uptake on oatp1 has not been identified, although a role for bicarbonate has
      recently been proposed. The present study examined whether oatp1-mediated uptake
      is energized by efflux (countertransport) of intracellular reduced glutathione
      (GSH), and whether hydrophobic glutathione S-conjugates such as leukotriene C4
      (LTC4) and S-dinitrophenyl glutathione (DNP-SG) form a novel class of substrates
      for oatp1. Xenopus laevis oocytes injected with the complementary RNA for oapt1
      demonstrated higher uptake of 10 nM [3H]LTC4 and 50 microM [3H]DNP-SG, and higher
      efflux of [3H]GSH (2.5 mM endogenous intracellular GSH concentration). The oatp1
      stimulated LTC4 and DNP-SG uptake was independent of the Na+ gradient, cis
      inhibited by known substrates of this transport protein and by 1 mM GSH, and was
      saturable, with apparent Km values of 0.27 +/- 0.06 and 408 +/- 95 microM,
      respectively. Uptake of [3H]taurocholate, an endogenous substrate of oatp1, was
      competitively inhibited by DNP-SG. Of significance, oatp1-mediated taurocholate
      and LTC4 uptake was cis-inhibited and trans-stimulated by GSH, and [3H]GSH efflux
      was enhanced in the presence of extracellular taurocholate or
      sulfobromophthalein, indicating that GSH efflux down its large electrochemical
      gradient provides the driving force for uptake via oatp1. The stoichiometry of
      GSH/taurocholate exchange was 1:1. These findings identify a new class of
      substrates for oatp1 and provide evidence for GSH-dependent oatp1-mediated
      substrate transport.

PMID- 9632675
TI  - The Plasmodium falciparum translationally controlled tumor protein homolog and
      its reaction with the antimalarial drug artemisinin.
AB  - Artemisinin and its derivatives are important new antimalarial drugs. When
      Plasmodium falciparum-infected erythrocytes are incubated with [10
      3H]dihydroartemisinin, several malaria-specific proteins become labeled. One of
      these proteins is the P. falciparum translationally controlled tumor protein
      (TCTP) homolog. In vitro, dihydroartemisinin reacts covalently with recombinant
      TCTP in the presence of hemin. The association between drug and protein increases
      with increasing drug concentration, plateauing at approximately 1 drug/TCTP
      molecule. By Scatchard analysis, there appear to be 2 hemin binding sites on TCTP
      with dissociation constants of approximately 18 microM. When the single cysteine
      moiety is blocked by pretreatment with iodoacetamide, hemin binding is not
      affected, whereas drug binding is reduced by two-thirds. Thus, TCTP reacts with
      artemisinin in situ and in vitro in the presence of hemin and appears to bind to
      hemin. The function of the malarial TCTP and the role of this reaction in the
      mechanism of action of artemisinin await elucidation.

PMID- 9632676
TI  - The putative cofactor TIF1alpha is a protein kinase that is hyperphosphorylated
      upon interaction with liganded nuclear receptors.
AB  - Ligand-induced gene activation by nuclear receptors (NRs) is a complex process
      requiring dissociation of corepressors and recruitment of coactivators. The
      putative transcriptional intermediary factor TIF1alpha has been previously
      characterized as a nuclear protein that interacts directly with the AF-2 ligand
      dependent activating domain present in the ligand-binding domain of numerous
      steroid and nonsteroid receptors, including the estrogen (ERalpha) and retinoid X
      (RXRalpha) receptors. We report here that TIF1alpha is both a phosphoprotein and
      a protein kinase. TIF1alpha coexpressed in COS-1 cells with RXRalpha or ERalpha
      is phosphorylated and becomes hyperphosphorylated upon ligand treatment. This
      hyperphosphorylation requires the binding of TIF1alpha to transcriptionally
      active NRs since it is prevented by mutations either in the core (alpha-helix 12
      of the ligand-binding domain) of the AF-2 activating domains of RXRalpha and
      ERalpha or in the NR box of TIF1alpha that are known to prevent TIF1alpha-NR
      interactions. Thus, TIF1alpha is a phosphoprotein that undergoes ligand-dependent
      hyperphosphorylation as a consequence of nuclear receptor binding. We further
      show that purified recombinant TIF1alpha possesses intrinsic kinase activity and
      that, in addition to autophosphorylation, TIF1alpha selectively phosphorylates
      the transcription factors TFIIEalpha, TAFII28, and TAFII55 in vitro. These latter
      results raise the possibility that TIF1alpha may act, at least in part, by
      phosphorylating and modifying the activity of components of the transcriptional
      machinery.

PMID- 9632677
TI  - Expressed protein ligation, a novel method for studying protein-protein
      interactions in transcription.
AB  - Expressed protein ligation is a novel protein semi-synthesis method that permits
      the in vitro ligation of a chemically synthesized C-terminal segment of a protein
      to a recombinant N-terminal segment fused through its C terminus to an intein
      protein splicing element. In principle, the practical convenience of this method,
      combined with the expanded opportunities in protein engineering that it provides,
      makes it well suited for probing the molecular basis of complex processes such as
      transcription. Here we describe the successful application of expressed protein
      ligation to the approximately 600 amino acid sigma70 subunit of Escherichia coli
      RNA polymerase. The resulting semi-synthetic sigma70 constructs are shown to be
      fully functional and have been used to map the binding region of the
      bacteriophage T4 anti-sigma protein, AsiA, to within amino acids 567-600 of
      sigma70. The success of these semi-synthesis studies sets the stage for the
      future generation of semi-synthetic sigma70 molecules in which unnatural amino
      acids and biophysical probes are site-specifically incorporated in the RNA
      polymerase complex.

PMID- 9632678
TI  - Biochemical studies of the mechanism of action of the Cdc42-GTPase-activating
      protein.
AB  - The small GTP-binding proteins Rac, Rho, and Cdc42 were shown to mediate a
      variety of signaling pathways including cytoskeletal rearrangements, cell-cycle
      progression, and transformation. Key to the proper function of these GTP-binding
      proteins is an efficient shut-off mechanism that ensures the decay of the signal.
      Regulatory proteins termed GAPs (GTPase-activating proteins) enhance the
      intrinsic GTP hydrolysis of the GTP-binding proteins, thereby ensuring signal
      termination. We have used site-specific mutagenesis to elucidate the limit domain
      for GAP activity in Cdc42-GAP, and show that in addition to the known GAP
      homology domain (three conserved boxes), a C-terminal region outside that domain
      is also essential for GAP activity. In addition, we have replaced the conserved
      arginine (Arg305), which was suggested by structural studies to be a key
      catalytic residue, with an alanine and found that the R305A Cdc42-GAP mutant has
      a greatly diminished catalytic capacity but is still able to bind Cdc42 with high
      affinity. Thus, a key catalytic role for this residue is confirmed. However, we
      also present evidence for the involvement of an additional residue(s), since the
      R305A Cdc42-GAP mutant still exhibits measurable activity. Some of this residual
      activity might result from a neighboring arginine, since a double mutant
      R305A/R306A shows a further decrease in catalytic activity.

PMID- 9632679
TI  - Unfolding of diphtheria toxin. Identification of hydrophobic sites exposed on
      lowering of pH by photolabeling.
AB  - We report here the use of a hydrophobic photoactivable reagent, 2
      [3H]diazofluorene (DAF), to map the hydrophobic sites exposed when the pH is
      lowered in diphtheria toxin (DT). The reagent binds to DT, and on photolysis with
      light of wavelength >350 nm, it covalently attaches itself to DT. The labeling
      was observed to increase considerably when the pH was lowered from 7.4 to 5.2.
      Although both A- and B-chains were labeled to a similar degree at pH 7.4, at
      lower pH (5.2), B-chain was labeled to a much higher extent. Subsequent chemical
      and enzymatic fragmentation of DT followed by separation indicated that the
      putative transmembrane domain was labeled to its maximum extent at pH 5.2, with
      the bulk of labeling associated with residues 340-459. Protein sequencing
      analysis indicated that the two buried hydrophobic helices, identified in the
      crystal structure and suggested to insert and span the membrane bilayer,
      corresponding to residues 326-347 and 358-376, are strongly labeled. The Pro-345
      residue was observed to be labeled maximally at lower pH values. Finally, the DAF
      labeling pattern indicated that the parent structural motifs are retained at low
      pH, suggesting that the low pH conformation of DT corresponds to an equilibrium
      molten globule state.

PMID- 9632680
TI  - Purification and characterization of hamster liver microsomal 7alpha
      hydroxycholesterol dehydrogenase. Similarity to type I 11beta-hydroxysteroid
      dehydrogenase.
AB  - While studying the bile acid synthetic pathway of hamsters, we discovered an
      NADP+-dependent liver microsomal 7alpha-hydroxycholesterol dehydrogenase (7alpha
      HCD) activity that was not observed in rat liver microsomal fractions. The
      hamster liver microsomal 7alpha-HCD was purified to homogeneity using 2', 5'-ADP
      and cholic acid-agarose affinity chromatography. 7alpha-HCD displayed a molecular
      weight of approximately 34,000 on SDS-polyacrylamide gel electrophoresis; it is
      an intrinsic membrane protein of the hamster liver endoplasmic reticulum and
      exists as a multimeric aggregate in pure form. Partial N-terminal amino acid
      sequence analysis showed that 7alpha-HCD had high sequence similarity to human
      11beta-hydroxysteroid dehydrogenase (11beta-HSD; 24/30 amino acid identity). The
      Km values for corticosterone and 7alpha-hydroxycholesterol were 1.2 and 1.9
      microM, respectively, for purified 7alpha-HCD; both reactions displayed identical
      Vmax values (approximately 170 nmol/min/mg of protein). The IC50 of
      carbenoxolone, a competitive inhibitor of 11beta-HSD, was 75 nM for 7alpha
      hydroxycholesterol dehydrogenation and 210 nM for corticosterone dehydrogenation.
      The tissue-specific expression in hamster was as follows: adrenal >/= liver >
      kidney > testis >> brain > lung. Microsomal 7alpha-HCD is uniquely expressed in
      hamster liver and to some extent in human liver but not in rat liver. Western
      blot analysis with two antibodies elicited against an N-terminal peptide of the
      human 11beta-HSD and purified hamster liver 7alpha-HCD, respectively, suggested
      the presence of multiple forms of 7alpha-HCD in hamster liver, most likely due to
      the existence of a family of 11beta-HSD proteins. Since 7-oxocholesterol is a
      potent inhibitor of cholesterol 7alpha-hydroxylase, alternative mechanisms for
      regulation of bile acid synthesis may exist in human and hamster liver due to
      production of this metabolite and its potential as an oxysterol.

PMID- 9632681
TI  - Insertion scanning mutagenesis of subunit a of the F1F0 ATP synthase near His245
      and implications on gating of the proton channel.
AB  - Subunit a of the E. coli F1F0 ATP synthase was probed by insertion scanning
      mutagenesis in a region between residues Glu219 and His245. A series of single
      amino acid insertions, of both alanine and aspartic acid, were constructed after
      the following residues: 225, 229, 233, 238, 243, and 245. The mutants were tested
      for growth yield, binding of F1 to membranes, dicyclohexylcarbodiimide
      sensitivity of ATPase activity, ATP-driven proton translocation, and passive
      proton permeability of membranes stripped of F1. Significant loss of function was
      seen only with insertions after positions 238 and 243. In contrast, both
      insertions after residue 225 and the alanine insertion after residue 245 were
      nearly identical in function to the wild type. The other insertions showed an
      intermediate loss of function. Missense mutations of His245 to serine and
      cysteine were nonfunctional, while the W241C mutant showed nearly normal ATPase
      function. Replacement of Leu162 by histidine failed to suppress the 245 mutants,
      but chemical rescue of H245S was partially successful using acetate. An
      interaction between Trp241 and His245 may be involved in gating a "half-channel"
      from the periplasmic surface of F0 to Asp61 of subunit a.

PMID- 9632682
TI  - Membrane topology of subunit a of the F1F0 ATP synthase as determined by labeling
      of unique cysteine residues.
AB  - The membrane topology of the a subunit of the F1F0 ATP synthase from Escherichia
      coli has been probed by surface labeling using 3-(N-maleimidylpropionyl)
      biocytin. Subunit a has no naturally occurring cysteine residues, allowing unique
      cysteines to be introduced at the following positions: 8, 24, 27, 69, 89, 128,
      131, 172, 176, 196, 238, 241, and 277 (following the COOH-terminal 271 and a
      hexahistidine tag). None of the single mutations affected the function of the
      enzyme, as judged by growth on succinate minimal medium. Membrane vesicles with
      an exposed cytoplasmic surface were prepared using a French pressure cell. Before
      labeling, the membranes were incubated with or without a highly charged
      sulfhydryl reagent, 4-acetamido-4'-maleimidylstilbene-2,2'-disulfonic acid. After
      labeling with the less polar biotin maleimide, the samples were solubilized with
      octyl glucoside/cholate and the subunit a was purified via the oligohistidine at
      its COOH terminus using immobilized nickel chromatography. The purified samples
      were electrophoresed and transferred to nitrocellulose for detection by avidin
      conjugated to alkaline phosphatase. Results indicated cytoplasmic accessibility
      for residues 69, 172, 176, and 277 and periplasmic accessibility for residues 8,
      24, 27, and 131. On the basis of these and earlier results, a transmembrane
      topology for the subunit a is proposed.

PMID- 9632683
TI  - Transmembrane topography of subunit a in the Escherichia coli F1F0 ATP synthase.
AB  - Subunit a is the least understood of the three subunits that compose the F0
      sector in the Escherichia coli F0F1 ATP synthase. In this study, we have
      substituted Cys into predicted extramembranous loops of the protein and used
      chemical modification to obtain topographical information on the folding of
      subunit a. The extent of labeling of the substituted Cys residues by fluorescein
      5'-maleimide was determined. The localization of reactive Cys residues was
      inferred from differences in the extent of labeling in inside out and right side
      out membrane vesicles. The NH2-terminal segment of subunit a was localized to the
      outside (periplasmic) surface and the COOH terminus to the cytoplasmic surface by
      these procedures. Loop residues in two periplasmic extramembranous loops and in
      two cytoplasmic extramembranous loops were also localized. The localization of
      two cytoplasmic Cys residues was confirmed by using 4-acetamido-4'
      maleimidylstilbene-2,2'-disulfonic acid to block fluorescein-5'-maleimide
      labeling. From the localization of the Cys residues, a model for the topography
      is proposed that consists of five transmembrane segments with the NH2 terminus
      periplasmic and the COOH terminus cytoplasmic. The positions of second site
      suppressors, including several isolated here to the nonfunctional E219C and H245C
      substitutions, provide support for the topographical model proposed.

PMID- 9632684
TI  - Conformational changes in conantokin-G induced upon binding of calcium and
      magnesium as revealed by NMR structural analysis.
AB  - The apo- and metal-bound solution conformations of synthetic conantokin-G (con-G,
      G1Egamma gammaL5Q gamma NQgamma 10LIRgamma K15SN-CONH2, gamma = gamma
      carboxyglutamic acid), an antagonist of N-methyl-D-aspartate receptor-derived
      neuronal ion channels, have been examined by one- and two-dimensional 1H NMR at
      neutral pH. A complete structure for the Mg2+-loaded peptide was defined by use
      of distance geometry calculations and was found to exist as an alpha-helix that
      spans the entire peptide. The alpha-helical nature of Mg2+/con-G was also
      supported by the small values (<5.5 Hz) of the 3JHNalpha coupling constants
      measured for amino acid residues 3-5, 8, 9, and 11-16, and the small values (<4
      ppb/K) of the temperature coefficients observed for the alphaNH protons of
      residues 5-17. This conformation contrasted with that obtained for apo-con-G,
      which was nearly structureless in solution. Docking of Mg2+ into con-G was
      accomplished by use of the genetic algorithm/molecular dynamics simulation
      method, employing the NMR-derived Mg2+-loaded structure for initial coordinates
      in the midpoint calculations. For the 3 Mg2+/con-G model, it was found that
      binding of one Mg2+ ion is stabilized by oxygen atoms from three gamma
      carboxylates of Gla3, Gla4, and Gla7; another Mg2+ is coordinated by two oxygen
      atoms, one from each of the gamma-carboxylates of Gla7; and a third metal ion
      through three donor oxygen atoms of gamma-carboxylates from Gla10 and Gla14. As
      shown from direct metal binding measurements to mutant con-G peptides, these
      latter two Gla residues probably stabilized the tightest binding Mg2+ ion.
      Circular dichroism studies of these same peptide variants demonstrated that all
      Gla residues contribute to the adoption of the Mg2+-dependent alpha-helical
      conformation in con-G. The data obtained in this investigation provide a
      molecular basis for the large conformational alteration observed in apo-con-G as
      a result of divalent cation binding and allow assessment of the roles of
      individual Gla residues in defining certain of the structure-function properties
      of con-G.

PMID- 9632685
TI  - A specific binding protein for cardiac glycosides exists in bovine serum.
AB  - Searching for a binding protein in blood, which may be involved in the specific
      transport of cardiac glycosides to their receptor sites on the sodium pump, we
      isolated a cardiac glycoside-binding protein (CGBG) of 26 kDa from the globulin
      fraction of bovine serum by affinity chromatography and on a ouabain-Sepharose 4B
      column by a purification factor of 5000. The cardiac glycoside-binding globulin
      was labeled specifically and covalently by the protein-reactive digoxigenin
      derivative HDMA (N-hydroxysuccimidyldigoxigenin-3-O-methylcarbonyl-epsilon-+
      ++aminocapro ate). Even very high concentrations of other steroids, such as
      estrogen, testosterone, progesterone, and cortisone, did not prevent HDMA
      labeling (at 5 and 100 nM) of CGBG, but the cardenolides ouabain and digoxin or
      the bufadienolide proscillaridin A did so. CGBG is a homodimer of two 26-kDa
      subunits forming disulfide bonds, since HDMA labeling of a protein of 53 kDa was
      observed in SDS-polyacrylamide gel electrophoresis when beta-mercaptoethanol was
      absent during SDS denaturation. The N-terminal amino acid sequence K-D-V-Y-R-A-P
      D-G-T-Q-S-A showed no sequence similarity with proteins recorded in gene and
      protein sequence data banks. A 90-kDa cytosolic CGBG exists in bovine kidneys and
      reacts with antibodies against CGBG. Binding of ouabain to the cardiac glycoside
      binding globulin was monitored by quenching of intrinsic tryptophan fluorescence.
      Such studies reveal two negatively cooperative ouabain binding sites with Kd' of
      1.52 nM and Kd' = 75 nM and with an interaction factor of 50 using a Koshland
      Nemethy-Filmer model. The demonstration of a cardiac glycoside-binding globulin
      in plasma is consistent with the recent finding of endogenous cardiac glycosides
      in mammals.

PMID- 9632686
TI  - Sites for Galpha binding on the G protein beta subunit overlap with sites for
      regulation of phospholipase Cbeta and adenylyl cyclase.
AB  - Heterotrimeric G proteins, composed of alpha and betagamma subunits, forward
      signals from transmembrane receptors to intracellular effector enzymes and ion
      channels. Free betagamma activates downstream targets, but its action is
      terminated by association with GDP-liganded alpha subunits. Because alpha can
      inhibit activation of many effectors by betagamma, it is likely that the alpha
      subunit binding surfaces on betagamma overlap the surfaces necessary for effector
      activation. To test this hypothesis, we mutated residues on beta shown to contact
      alpha in the recently published crystal structures of the alphabetagamma
      heterotrimer (Wall, M. A., Coleman, D. E., Lee, E., Iniguez-Lluhi, J. A., Posner,
      B. A., Gilman, A. G., and Sprang, S. R. (1995) Cell 83, 1047-1058; Lambright, D.
      G., Sondek, J., Bohm, A., Skiba, N. P., Hamm, H. E., and Sigler, P. B. (1996)
      Nature 379, 311-319.). The alpha subunit binds to the flat, top surface of the
      toroidal beta subunit and also extends a helix along the side of the beta subunit
      at blade 1. We mutated four residues on the top surface of beta (Hbeta1[L117A],
      Hbeta1[D228R], Hbeta1[D246S], and Hbeta1[W332A]) and two residues on the side of
      beta that contacts alpha (Hbeta1[N88A/K89A]). Each of the mutant proteins was
      able to form beta gamma dimers, but they differed in their ability to bind alpha
      and to activate phospholipase C beta2 (PLCbeta2), PLCbeta3, and adenylyl cyclase
      II. Mutation of residues along the side of the torus at blade 1 diminish affinity
      for alpha but do not prevent activation of any of the effectors. Mutations on the
      alpha binding surface differentially affected PLCbeta2, PLCbeta3, and adenylyl
      cyclase II. Residues that affect PLCbeta and adenylyl cyclase II activity are
      found on opposite sides of the central tunnel, suggesting that PLC and adenylyl
      cyclase, like the alpha subunit, make many contacts on the top surface. None of
      the mutations affected the ability of betagamma to inhibit adenylyl cyclase I. We
      conclude that alpha, PLCbeta2, PLCbeta3, and adenylyl cyclase II share an
      interaction on the top surface of beta. The importance of individual residues is
      different for alpha binding and for effector activation and differs even between
      closely related isoforms of the same effector.

PMID- 9632687
TI  - Role of electrostatic interactions on the affinity of thioredoxin for target
      proteins. Recognition of chloroplast fructose-1, 6-bisphosphatase by mutant
      Escherichia coli thioredoxins.
AB  - Chloroplast thioredoxin-f functions efficiently in the light-dependent activation
      of chloroplast fructose-1, 6-bisphosphatase by reducing a specific disulfide bond
      located at the negatively charged domain of the enzyme. Around the nucleophile
      cysteine of the active site (-W-C-G-P-C-), chloroplast thioredoxin-f shows lower
      density of negative charges than the inefficient modulator Escherichia coli
      thioredoxin. To examine the contribution of long range electrostatic interactions
      to the thiol/disulfide exchange between protein-disulfide oxidoreductases and
      target proteins, we constructed three variants of E. coli thioredoxin in which an
      acidic (Glu-30) and a neutral residue (Leu-94) were replaced by lysines. After
      purification to homogeneity, the reduction of the unique disulfide bond by NADPH
      via NADP-thioredoxin reductase proceeded at similar rates for all variants.
      However, the conversion of cysteine residues back to cystine depended on the
      target protein. Insulin and difluoresceinthiocarbamyl-insulin oxidized the
      sulfhydryl groups of E30K and E30K/L94K mutants more effectively than those of
      wild type and L94K counterparts. Moreover, the affinity of E30K, L94K, and
      E30K/L94K E. coli thioredoxin for chloroplast fructose-1,6-bisphosphatase (A0.5 =
      9, 7, and 3 microM, respectively) increased with the number of positive charges,
      and was higher than wild type thioredoxin (A0.5 = 33 microM), though still lower
      than that of thioredoxin-f (A0.5 = 0.9 microM). We also demonstrated that
      shielding of electrostatic interactions with high salt concentrations not only
      brings the A0.5 for all bacterial variants to a limiting value of approximately 9
      microM but also increases the A0.5 of chloroplast thioredoxin-f. While negatively
      charged chloroplast fructose-1,6-bisphosphatase (pI = 4.9) readily interacted
      with mutant thioredoxins, the reduction rate of rapeseed napin (pI = 11.2)
      diminished with the number of novel lysine residues. These findings suggest that
      the electrostatic interactions between thioredoxin and (some of) its target
      proteins controls the formation of the binary noncovalent complex needed for the
      subsequent thiol/disulfide exchange.

PMID- 9632688
TI  - Regulation of brain G-protein go by Alzheimer's disease gene presenilin-1.
AB  - To investigate a possible association between G-proteins and presenilin-1 (PS-1),
      a series of glutathione S-transferase-fusion proteins containing portions of PS-1
      were prepared and used in vitro in binding experiments with tissue and
      recombinant G-proteins. The results demonstrate that the 39 C-terminal amino
      acids of PS-1 selectively bind the brain G-protein, Go. Addition of guanosine 5'
      3-O-(thio)triphosphate promoted Go dissociation from PS-1, indicating that this
      domain mimics the function of G-protein-coupling domains found in receptors. The
      39-amino acid synthetic polypeptide activated Go in a magnesium ion-dependent
      manner. Physical interaction of full-length PS-1 and Go was also demonstrated.
      Following transfection of Goalpha and N-terminally FLAG-tagged PS-1 in COS-7
      cells, Go was immunoprecipitated by FLAG antibodies. In addition, endogenous PS-1
      and Goalpha were colocalized immunocytochemically in human glioma cell lines. The
      results indicate that PS-1 regulates Go activities in living cells.

PMID- 9632689
TI  - The beta subunit of the high conductance calcium-activated potassium channel.
      Identification of residues involved in charybdotoxin binding.
AB  - Coexpression of alpha and beta subunits of the high conductance Ca2+-activated K+
      (maxi-K) channel leads to a 50-fold increase in the affinity for 125I
      charybdotoxin (125I-ChTX) as compared with when the alpha subunit is expressed
      alone (Hanner, M., Schmalhofer, W. A., Munujos, P., Knaus, H.-G., Kaczorowski, G.
      J., and Garcia, M. L. (1997) Proc. Natl. Acad. Sci. U. S. A. 94, 2853-2858). To
      identify those residues in the beta subunit that are responsible for this change
      in binding affinity, Ala scanning mutagenesis was carried out along the
      extracellular loop of beta, and the resulting effects on 125I-ChTX binding were
      determined after coexpression with the alpha subunit. Mutagenesis of each of the
      four Cys residues present in the loop causes a large reduction in toxin binding
      affinity, suggesting that these residues could be forming disulfide bridges. The
      existence of two disulfide bridges in the extracellular loop of beta was
      demonstrated after comparison of reactivities of native beta and single-Cys
      mutated subunits to N-biotin-maleimide. Negatively charged residues in the loop
      of beta, when mutated individually or in combinations, had no effect on toxin
      binding with the exception of Glu94, whose alteration modifies kinetics of ligand
      association and dissociation. Further mutagenesis studies targeting individual
      residues between Cys76 and Cys103 indicate that four positions, Leu90, Tyr91,
      Thr93, and Glu94 are critical in conferring high affinity 125I-ChTX binding to
      the alpha.beta subunit complex. Mutations at these positions cause large effects
      on the kinetics of ligand association and dissociation, but they do not alter the
      physical interaction of beta with the alpha subunit. All these data, taken
      together, suggest that the large extracellular loop of the maxi-K channel beta
      subunit has a restricted conformation. Moreover, they are consistent with the
      view that four residues appear to be important for inducing an appropriate
      conformation within the alpha subunit that allows high affinity ChTX binding.

PMID- 9632690
TI  - Mutations in the hydrophobic surface of an amphipathic groove of 14-3-3zeta
      disrupt its interaction with Raf-1 kinase.
AB  - 14-3-3 proteins bind to a diverse group of regulatory molecules such as Raf-1,
      Cbl, and c-Bcr that are involved in signal transduction pathways. The crystal
      structure of 14-3-3zeta reveals a conserved amphipathic groove that may mediate
      the association of 14-3-3 with diverse ligands. Consistently, mutations on the
      charged surface of the groove (Lys-49, Arg-56, and Arg-60) decrease the binding
      of 14-3-3zeta to the ligands tested (Zhang, L., Wang, H., Liu, D., Liddington,
      R., and Fu, H. (1997) J. Biol. Chem. 272, 13717-13724). Here we report that
      mutations that altered the hydrophobic property of the groove, V176D, L216D,
      L220D, and L227D, disrupted the interaction of 14-3-3zeta with Raf-1 kinase. The
      reduced binding of the 14-3-3zeta mutants to Raf-1 was apparently not because of
      gross structural changes in the mutants as judged by their ability to form
      dimers, by partial proteolysis profiles, and by circular dichroism analysis.
      These hydrophobic residues appeared to be required for the binding of 14-3-3zeta
      to distinct activation states of Raf-1 because mutations V176D, L216D, L220D, and
      L227D reduced the interaction of 14-3-3zeta with Raf-1 from both phorbol 12
      myristate 13-acetate-stimulated and unstimulated Jurkat T cells. These same
      mutations also disrupted the association of 14-3-3zeta with other regulatory
      molecules such as Cbl and c-Bcr, suggesting that the hydrophobic surface of the
      amphipathic groove represents part of a binding site shared by a number of 14-3-3
      associated proteins. The conservation of the hydrophobic residues Val-176, Leu
      216, Leu-220, and Leu-227 among known 14-3-3 family members implies their general
      importance in ligand binding.

PMID- 9632691
TI  - 14-3-3zeta binds a phosphorylated Raf peptide and an unphosphorylated peptide via
      its conserved amphipathic groove.
AB  - 14-3-3 proteins bind a variety of molecules involved in signal transduction, cell
      cycle regulation and apoptosis. 14-3-3 binds ligands such as Raf-1 kinase and Bad
      by recognizing the phosphorylated consensus motif, RSXpSXP, but must bind
      unphosphorylated ligands, such as glycoprotein Ib and Pseudomonas aeruginosa
      exoenzyme S, via a different motif. Here we report the crystal structures of the
      zeta isoform of 14-3-3 in complex with two peptide ligands: a Raf-derived
      phosphopeptide (pS-Raf-259, LSQRQRSTpSTPNVHMV) and an unphosphorylated peptide
      derived from phage display (R18, PHCVPRDLSWLDLEANMCLP) that inhibits binding of
      exoenzyme S and Raf-1. The two peptides bind within a conserved amphipathic
      groove on the surface of 14-3-3 at overlapping but distinct sites. The
      phosphoserine of pS-Raf-259 engages a cluster of basic residues (Lys49, Arg56,
      Arg60, and Arg127), whereas R18 binds via the amphipathic sequence, WLDLE, with
      its two acidic groups coordinating the same basic cluster. 14-3-3 is dimeric, and
      its two peptide-binding grooves are arranged in an antiparallel fashion, 30 A
      apart. The ability of each groove to bind different peptide motifs suggests how
      14-3-3 can act in signal transduction by inducing either homodimer or heterodimer
      formation in its target proteins.

PMID- 9632692
TI  - Dual role for adenine nucleotides in the regulation of the atrial natriuretic
      peptide receptor, guanylyl cyclase-A.
AB  - The ability to both sensitize and desensitize a guanylyl cyclase receptor has not
      been previously accomplished in a broken cell or membrane preparation. The
      guanylyl cyclase-A (GC-A) receptor is known to require both atrial natriuretic
      peptide (ANP) and an adenine nucleotide for maximal cyclase activation. When
      membranes from NIH 3T3 cells stably overexpressing GC-A were incubated with ATP,
      AMPPNP, or ATPgammaS, only ATPgammaS dramatically potentiated ANP-dependent
      cyclase activity. When the membranes were incubated with ATPgammaS and then
      washed, GC-A now became sensitive to ANP/AMPPNP stimulation, suggestive that
      thiophosphorylation had sensitized GC-A to ligand and adenine nucleotide binding.
      Consistent with this hypo- thesis, the ATPgammaS effects were both time- and
      concentration-dependent. Protein phosphatase stability of thiophosphorylation
      (ATPgammaS) relative to phosphorylation (ATP) appeared to explain the
      differential effects of the two nucleotides since microcystin, beta-glycerol
      phosphate, or okadaic acid coincident with ATP or ATPgammaS effectively
      sensitized GC-A to ligand stimulation over prolonged periods of time in either
      case. GC-A was phosphorylated in the presence of [gamma32P]ATP, and the magnitude
      of the phosphorylation was increased by the addition of microcystin. Thus, the
      phosphorylation of GC-A correlates with the acquisition of ligand sensitivity.
      The establishment of an in vitro system to sensitize GC-A demonstrates that
      adenine nucleotides have a daul function in the regulation of GC-A through both
      phosphorylation of and binding to regulatory sites.

PMID- 9632693
TI  - Cells of the neuronal lineage play a major role in the generation of amyloid
      precursor fragments in gelsolin-related amyloidosis.
AB  - Gelsolin-related amyloidosis or familial amyloidosis, Finnish type (FAF) (OMIM
      No105120) is a hereditary amyloid disease caused by a mutation in a precursor
      protein for amyloid (gelsolin) and characterized by corneal dystrophy and
      polyneuropathy. In vitro expression of the FAF-mutant (Asp187 --> Asn/Tyr)
      secretory gelsolin in COS cells leads to generation of an aberrant polypeptide
      presumably representing the precursor for tissue amyloid. Here, we provide
      evidence that this abnormal processing results from defective initial folding of
      the secreted FAF gelsolin due to the lack of the Cys188-Cys201 disulfide bond,
      normally formed next to the FAF mutation site. We compared cells of different
      tissue origin and discovered a dramatic difference between the amount of cleavage
      of FAF gelsolin to the amyloid precursor in neuronal and non-neuronal cells. More
      than half of the mutant gelsolin was cleaved in PC12 and in vitro differentiated
      human neuronal progenitor cells. In contrast, human fibroblasts and Schwannoma
      cell cultures showed only a limited capacity to cleave FAF gelsolin, although the
      cleavage mechanism per se seems to be similar in the various cell types. The
      present findings of processing and distribution of secreted FAF gelsolin in the
      neuronal cells emphasize the role of neurons in the tissue pathogenesis of this
      amyloid polyneuropathy.

PMID- 9632694
TI  - The effect of Me2+ cofactors at the initial stages of V(D)J recombination.
AB  - V(D)J site-specific recombination mediates the somatic assembly of the antigen
      receptor gene segments. This process is initiated by the recombination activating
      proteins RAG1 and RAG2, which recognize the recombination signal sequences (RSS)
      and cleave the DNA at the coding/RSS junction. In this study, we show that RAG1
      and RAG2 have the ability to directly interact in solution before binding to the
      DNA. RAG1 forms a homodimer, which leads to the appearance of two distinct
      RAG1.RAG2 complexes bound to DNA. To investigate the properties of the two
      RAG1.RAG2 complexes in the presence of different Me2+ cofactors, we established
      an in vitro Mg2+-based cleavage reaction on a single RSS. Using this system, we
      found that Mg2+ confers a specific pattern of DNA binding and cleavage. In
      contrast, Mn2+ allows aberrant binding of RAG1.RAG2 to single-stranded RSS and
      permits cleavage independent of binding to the nonamer. To determine the
      contribution of Me2+ ions at the early stages of V(D)J recombination, we analyzed
      specific DNA recognition and cleavage by RAG1.RAG2 on phosphorothioated
      substrates. These experiments revealed that Me2+ ions directly coordinate the
      binding of RAG1.RAG2 to the RSS DNA.

PMID- 9632695
TI  - Exchange of substrate and inhibitor specificities between adenylyl and guanylyl
      cyclases.
AB  - The active sites of guanylyl and adenylyl cyclases are closely related. The
      crystal structure of adenylyl cyclase and modeling studies suggest that
      specificity for ATP or GTP is dictated in part by a few amino acid residues,
      invariant in each family, that interact with the purine ring of the substrate. By
      exchanging these residues between guanylyl cyclase and adenylyl cyclase, we can
      completely change the nucleotide specificity of guanylyl cyclase and convert
      adenylyl cyclase into a nonselective purine nucleotide cyclase. The activities of
      these mutant enzymes remain fully responsive to their respective stimulators,
      sodium nitroprusside and Gsalpha. The specificity of nucleotide inhibitors of
      guanylyl and adenylyl cyclases that do not act competitively with respect to
      substrate are similarly altered, indicative of their action at the active sites
      of these enzymes.

PMID- 9632696
TI  - The mechanism of action of steroidogenic acute regulatory protein (StAR). StAR
      acts on the outside of mitochondria to stimulate steroidogenesis.
AB  - Steroidogenic acute regulatory protein (StAR) plays an essential role in
      steroidogenesis, facilitating delivery of cholesterol to cytochrome P450scc on
      the inner mitochondrial membrane. StAR is synthesized in the cytoplasm and is
      subsequently imported by mitochondria and processed to a mature form by cleavage
      of the NH2-terminal mitochondrial targeting sequence. To explore the mechanism of
      StAR action, we produced 6-histidine-tagged N-62 StAR (His-tag StAR) constructs
      lacking the NH2-terminal 62 amino acids that encode the mitochondrial targeting
      sequence and examined their steroidogenic activity in intact cells and on
      isolated mitochondria. His-tag StAR proteins stimulated pregnenolone synthesis to
      the same extent as wild-type StAR when expressed in COS-1 cells transfected with
      the cholesterol side-chain cleavage system. His-tag StAR was diffusely
      distributed in the cytoplasm of transfected COS-1 cells whereas wild-type StAR
      was localized to mitochondria. There was no evidence at the light or electron
      microscope levels for selective localization of His-tag StAR protein to
      mitochondrial membranes. In vitro import assays demonstrated that wild-type StAR
      preprotein was imported and processed to mature protein that was protected from
      subsequent trypsin treatment. In contrast, His-tag StAR was not imported and
      protein associated with mitochondria was sensitive to trypsin. Using
      metabolically labeled COS-1 cells transfected with wild-type or His-tag StAR
      constructs, we confirmed that wild-type StAR preprotein was imported and
      processed by mitochondria, whereas His-tag StAR remained largely cytosolic and
      unprocessed. To determine whether cytosolic factors are required for StAR action,
      we developed an assay system using washed mitochondria isolated from bovine
      corpora lutea and purified recombinant His-tag StAR proteins expressed in
      Escherichia coli. Recombinant His-tag StAR stimulated pregnenolone production in
      a dose- and time-dependent manner, functioning at nanomolar concentrations. A
      point mutant of StAR (A218V) that causes lipoid congenital adrenal hyperplasia
      was incorporated into the His-tag protein. This mutant was steroidogenically
      inactive in COS-1 cells and on isolated mitochondria. Our observations
      conclusively document that StAR acts on the outside of mitochondria, independent
      of mitochondrial import, and in the absence of cytosol. The ability to produce
      bioactive recombinant StAR protein paves the way for refined structural studies
      of StAR and StAR mutants.

PMID- 9632697
TI  - Co-localization of calcium-modulating cyclophilin ligand with intracellular
      calcium pools.
AB  - The calcium-modulating cyclophilin ligand (CAML) protein activates Ca2+ influx
      signaling when overexpressed in Jurkat T cells. Although CAML appears to directly
      participate in Ca2+-dependent signaling initiated by the transmembrane activator
      and CAML interactor cell surface receptor, its mechanism of action is unknown. To
      address this issue, we have determined its membrane topology, subcellular
      localization, and ability to mobilize intracellular Ca2+ pools. Fractionation of
      cell extracts on discontinuous sucrose gradients and indirect immunofluorescence
      indicate that CAML co-localizes with sarcoplasmic/endoplasmic reticulum
      calcium/ATPase-2 and calreticulin at membrane-bound cytosolic vesicles. Limited
      trypsin digests indicate that the hydrophilic NH2-terminal domain of CAML is
      directed toward the cytoplasm. Functionally, CAML overexpression was shown to
      deplete thapsigargin-sensitive intracellular Ca2+ pools. These data suggest that
      CAML may initiate Ca2+ signaling through activation of a capacitative Ca2+ influx
      pathway.

PMID- 9632698
TI  - Mutagenesis and modeling of the neurotensin receptor NTR1. Identification of
      residues that are critical for binding SR 48692, a nonpeptide neurotensin
      antagonist.
AB  - The two neurotensin receptor subtypes known to date, NTR1 and NTR2, belong to the
      family of G-protein-coupled receptors with seven putative transmembrane domains
      (TM). SR 48692, a nonpeptide neurotensin antagonist, is selective for the NTR1.
      In the present study we attempted, through mutagenesis and computer-assisted
      modeling, to identify residues in the rat NTR1 that are involved in antagonist
      binding and to provide a tentative molecular model of the SR 48692 binding site.
      The seven putative TMs of the NTR1 were defined by sequence comparison and
      alignment of bovine rhodopsin and G-protein-coupled receptors. Thirty-five amino
      acid residues within or flanking the TMs were mutated to alanine. Additional
      mutations were performed for basic residues. The wild type and mutant receptors
      were expressed in COS M6 cells and tested for their ability to bind 125I-NT and
      [3H]SR 48692. A tridimensional model of the SR 48692 binding site was constructed
      using frog rhodopsin as a template. SR 48692 was docked into the receptor, taking
      into account the mutagenesis data for orienting the antagonist. The model shows
      that the antagonist binding pocket lies near the extracellular side of the
      transmembrane helices within the first two helical turns. The data identify one
      residue in TM 4, three in TM 6, and four in TM 7 that are involved in SR 48692
      binding. Two of these residues, Arg327 in TM 6 and Tyr351 in TM 7, play a key
      role in antagonist/receptor interactions. The former appears to form an ionic
      link with the carboxylic group of SR 48692, as further supported by structure
      activity studies using SR 48692 analogs. The data also show that the agonist and
      antagonist binding sites in the rNTR1 are different and help formulate hypotheses
      as to the structural basis for the selectivity of SR 48692 toward the NTR1 and
      NTR2.

PMID- 9632699
TI  - Synthesis of polyribonucleotide chains from the 3'-hydroxyl terminus of
      oligodeoxynucleotides by Escherichia coli primase.
AB  - Escherichia coli primase synthesizes RNA primers on DNA templates for the
      initiation of DNA replication. The sole known activity of primase is to catalyze
      synthesis of short RNA chains de novo. We now report a novel activity of primase,
      namely that it can synthesize RNA from the 3'-hydroxyl terminus of a pre-existing
      oligodeoxynucleotide. The oligonucleotide-primed synthesis of RNA by primase
      occurs in both of the G4oric-specific priming system and the dnaB protein
      associated general priming system. This priming reaction of primase is verified
      by a number of biochemical methods, including inhibition by modified 3'-phosphate
      of oligonucleotides and deoxyribonuclease I and ribonuclease H cleavages. We also
      show that the primed RNA is an effective primer for the synthesis of DNA chain by
      E. coli DNA polymerase III holoenzyme. The significance of this finding to
      primases generating multimeric length RNA is discussed.

PMID- 9632700
TI  - Pervanadate stimulates amylase release and protein tyrosine phosphorylation of
      paxillin and p125(FAK) in differentiated AR4-2J pancreatic acinar cells.
AB  - We have studied the role of protein tyrosine phosphorylation in amylase secretion
      from differentiated AR4-2J cells. The secretagogue bombesin, the protein kinase C
      activator phorbol 12-myristate 13-acetate (PMA), and the protein-tyrosine
      phosphatase inhibitor pervanadate induced tyrosine phosphorylation of different
      proteins, including paxillin and p125(FAK), which was reduced or blocked by the
      tyrosine kinase inhibitors genistein and tyrphostin B56, respectively. Both PMA
      and pervanadate continuously increased amylase secretion with a similar time
      course, reaching the level of bombesin-induced amylase release after 60 min.
      Their effects were not additive and could be inhibited by preincubation of AR4-2J
      cells with genistein or tyrphostin B56, respectively. Inhibition of protein
      kinase C with Ro 31-8220 nearly abolished the effects of PMA, but had no effect
      on either pervanadate-induced protein tyrosine phosphorylation or amylase
      secretion. An increase in cytosolic free Ca2+ concentration by thapsigargin or
      A23187 caused a rapid increase in amylase release within the initial 5 min. In
      the presence of PMA or pervanadate, amylase secretion was further stimulated to
      levels comparable to those induced by bombesin after 30 min of stimulation.
      Inhibition of PMA-induced amylase secretion by Ro 31-8220 was less at elevated
      cytosolic free Ca2+ concentrations than without Ca2+. Furthermore, an increase in
      cytosolic free Ca2+ concentration had no effect on protein tyrosine
      phosphorylation in either the absence or presence of PMA or pervanadate. We
      therefore conclude that in the cascade of events that lead to bombesin-induced
      protein secretion from AR4-2J cells, protein tyrosine phosphorylation occurs
      downstream of protein kinase C activation. A further step in secretion that is
      Ca2+-dependent occurs distal to protein tyrosine phosphorylation.

PMID- 9632701
TI  - The import route of ADP/ATP carrier into mitochondria separates from the general
      import pathway of cleavable preproteins at the trans side of the outer membrane.
AB  - The ADP/ATP carrier (AAC) of the mitochondrial inner membrane is synthesized in
      the cytosol without a cleavable presequence. The preprotein preferentially binds
      to the mitochondrial surface receptor Tom70 and joins the import pathway of
      presequence-carrying preproteins at the cis side of the outer membrane. Little is
      known about the translocation of the AAC across the outer membrane and where its
      import route separates from that of cleavable preproteins. Here we have
      characterized a translocation intermediate of AAC during transfer across the
      outer membrane. The major portion of the preprotein is exposed to the
      intermembrane space, while a short segment is still accessible to externally
      added protease. This intermediate can be quantitatively chased to the fully
      imported form in the inner membrane. Its accumulation depends on Tom7, but not on
      the intermembrane space domain of Tom22 in contrast to cleavable preproteins.
      Moreover, opening of the intermembrane space inhibits the import of AAC, but not
      that of cleavable preproteins into mitoplasts. We conclude that the import route
      of AAC diverges from the general import pathway of cleavable preproteins already
      at the trans side of the outer membrane.

PMID- 9632702
TI  - A binding site for heparin in the apple 3 domain of factor XI.
AB  - Since heparin potentiates activated factor XI (FXIa) inhibition by protease nexin
      2 by providing a template to which both proteins bind (Zhang, Y., Scandura, J.
      M., Van Nostrand, W. E., and Walsh, P. N. (1997) J. Biol. Chem. 272, 26139
      26144), we examined binding of factor XI (FXI) and FXIa to heparin. FXIa binds to
      heparin (Kd approximately 0.7 x 10(-9) M) >150-fold more tightly than FXI (Kd
      approximately 1.1 x 10(-7) M). To localize the heparin-binding site on FXI,
      rationally designed conformationally constrained synthetic peptides were used to
      compete with 125I-FXI binding to heparin. A peptide derived from the Apple 3 (A3)
      domain of FXI (Asn235-Arg266) inhibited FXI binding to heparin (Kd approximately
      3.4 x 10(-6) M), whereas peptides from the A1 domain (Phe56-Ser86), A2 domain
      (Ala134-Ala176), and A4 domain (Ala317-Gly350) had no such effect. The
      recombinant A3 domain (rA3, Ala181-Val271) inhibited FXI binding to heparin (Ki
      approximately 1.4 x 10(-7) M) indicating that all the information necessary for
      FXI binding to heparin is contained entirely within the A3 domain. The A3 domain
      also contains a platelet-binding site (Asn235-Arg266), consisting of three
      surface-exposed loop structures, Pro229-Gln233, Thr741-Leu246, and Thr249-Phe260
      (Baglia, F. A., Jameson, B. A., and Walsh, P. N. (1995) J. Biol. Chem. 270, 6734
      6740). Only peptide Thr249-Phe260 (which contains a heparin binding consensus
      sequence, RIKKSKA) inhibits FXI binding to heparin (Ki = 2.1 x 10(-7) M), whereas
      peptides Pro229-Gln233 and Thr241- Leu246 had no effect. Fine mapping of the
      heparin-binding site using prekallikrein analogue amino acid substitutions of the
      synthetic peptide Thr249-Phe260 and alanine scanning of the recombinant A3
      indicated that the amino acids Lys252 and Lys253 are important for heparin
      binding. Thus, the sequence Thr249-Phe260 which contains most of the binding
      energy for FXI interaction with platelets also mediates the binding of FXI to
      heparin.

PMID- 9632703
TI  - Chicken ovalbumin upstream promoter-transcription factor (COUP-TF) modulates
      expression of the Purkinje cell protein-2 gene. A potential role for COUP-TF in
      repressing premature thyroid hormone action in the developing brain.
AB  - The cerebellar Purkinje cell-specific PCP-2 gene is transcriptionally activated
      by thyroid hormone during the 2nd and 3rd weeks of postnatal life in the rat. In
      contrast, thyroid hormone has no detectable effects on PCP-2 expression in the
      fetal rat. We now present data that suggest that the orphan nuclear receptor
      chicken ovalbumin upstream promoter-transcription factor (COUP-TF) represses
      triiodothyronine (T3)-dependent transcriptional activation of PCP-2 in the
      immature Purkinje cell. Gel shift assays show that the PCP-2 A1TRE and adjoining
      sequences (-295/-199 region) bind to rat and mouse brain nucleoproteins in a
      developmentally regulated fashion and that one of these nucleoproteins could be
      the orphan nucleoprotein COUP-TF. In support of this hypothesis, in vitro
      translated COUP-TF binds to the -295/-199 region and COUP-TF represses T3
      dependent activation of the PCP-2 promoter in transient transfection analyses.
      Finally, immunohistochemical studies reveal that COUP-TF is specifically
      expressed in the immature fetal and early neonatal Purkinje cell and that this
      expression diminishes coincident with thyroid hormone induction of PCP-2
      expression. Our findings are consistent with the hypothesis that the presence or
      absence of inhibitory proteins bound to the thyroid hormone response element of
      T3-responsive genes governs the responsivity of these genes to thyroid hormone
      during brain development.

PMID- 9632704
TI  - Leukocystatin, a new Class II cystatin expressed selectively by hematopoietic
      cells.
AB  - We describe a new cystatin in both mice and humans, which we termed
      leukocystatin. This protein has all the features of a Class II secreted
      inhibitory cystatin but contains lysine residues in the normally hydrophobic
      binding regions. As determined by cDNA library Southern blots, this cystatin is
      expressed selectively in hematopoietic cells, although fine details of the
      distribution among these cell types differ between the human and mouse mRNAs. In
      addition, we have determined the genomic organization of mouse leukocystatin, and
      we found that in contrast to most cystatins, the leukocystatin gene contains
      three introns. The recombinant proteins corresponding to these cystatins were
      expressed in Escherichia coli as N-terminal glutathione S-transferase or FLAGTM
      fusions, and studies showed that they inhibited papain and cathepsin L but with
      affinities lower than other cystatins. The unique features of leukocystatin
      suggests that this cystatin plays a role in immune regulation through inhibition
      of a unique target in the hematopoietic system.

PMID- 9632705
TI  - Protein kinase Cdelta mediates ethanol-induced up-regulation of L-type calcium
      channels.
AB  - Brief ethanol exposure inhibits L-type, voltage-gated calcium channels in neural
      cells, whereas chronic exposure increases the number of functional channels. In
      PC12 cells, this adaptive response is mediated by protein kinase C (PKC), but the
      PKC isozyme responsible is unknown. Since chronic ethanol exposure increases
      expression of PKCdelta and PKCepsilon, we investigated the role these isozymes
      play in up-regulation of L-type channels by ethanol. Incubation with the PKC
      inhibitor GF 109203X or expression of a PKCdelta fragment that inhibits phorbol
      ester-induced PKCdelta translocation largely prevented ethanol-induced increases
      in dihydropyridine binding and K+-stimulated 45Ca2+ uptake. A corresponding
      PKCepsilon fragment had no effect on this response. These findings indicate that
      PKCdelta mediates up-regulation of L-type channels by ethanol. Remaining
      responses to ethanol in cells expressing the PKCdelta fragment were not inhibited
      by GF 109203X, indicating that PKCdelta-independent mechanisms also contribute.
      PKCdelta overexpression increased binding sites for dihydropyridine and L-channel
      antagonists, but did not increase K+-stimulated 45Ca2+ uptake, possibly because
      of homeostatic responses that maintain base-line levels of channel function.
      Since L-type channels modulate drinking behavior and contribute to neuronal
      hyperexcitability during alcohol withdrawal, these findings suggest an important
      role for PKCdelta in alcohol consumption and dependence.

PMID- 9632706
TI  - Induction of apoptosis by SB202190 through inhibition of p38beta mitogen
      activated protein kinase.
AB  - p38, a subfamily of the mitogen-activated protein kinase, regulates gene
      expression in response to various extracellular stimuli. The pyridinyl imidazoles
      like SB202190 are specific inhibitors of p38alpha and p38beta and have been
      widely used in investigation of the biological functions of p38. Here we show
      that SB202190 by itself was sufficient to induce cell death, with typical
      apoptotic features such as nucleus condensation and intranucleosomal DNA
      fragmentation. SB202190 stimulated the activity of CPP32-like caspases, and its
      apoptotic effect was completely blocked by the protease inhibitor
      benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone and expression of bcl-2. In
      addition, SB202190 was able to potentiate apoptosis induced by Fas(APO-1)
      ligation or UV irradiation. Expression of p38beta attenuated the apoptotic effect
      of SB202190 and the cell death induced by Fas ligation and UV irradiation. In
      contrast, expression of p38alpha induced cell death mildly. These results
      indicate that SB202190 induces apoptosis through activation of CPP32-like
      caspases and suggest that distinct members of the p38 subfamily of mitogen
      activated protein kinase have different functions in apoptosis.

PMID- 9632707
TI  - Reduction of the major swine xenoantigen, the alpha-galactosyl epitope by
      transfection of the alpha2,3-sialyltransferase gene.
AB  - alpha2,3-Sialyltransferase represents a putative enzyme that reduces the
      Galalpha1-3Gal beta1-4GlcNAc-R (the alpha-galactosyl epitope) by intracellular
      competition with alpha1,3-galactosyltransferase for a common acceptor substrate.
      This study demonstrates that the overexpression of the alpha2,3-sialyltransferase
      gene suppresses the antigenicity of swine endothelial cells to human natural
      antibodies by 77% relative to control cells and by 30% relative to cells
      transfected with alpha1,2-fucosyltransferase, and in addition, it reduces the
      complement-mediated cell lysis by 75% compared with control cells and by 22%
      compared with cells transfected with alpha1, 2-fucosyltransferase. The mechanism
      by which the alpha-galactosyl epitope was reduced was also studied. Suppression
      of alpha1, 3-galactosyltransferase activity by 30-63% was observed in the
      transfectants with alpha2,3-sialyltransferase, and mRNA expression of the
      alpha1,3-galactosyltransferase gene was reduced as well. The data suggest that
      the alpha2,3-sialyltransferase effectively reduced the alpha-galactosyl epitope
      as well as or better than the alpha1, 2-fucosyltransferase did and that the
      reduction of the alpha-galactosyl epitope is due not only to substrate
      competition but also to an overall reduction of endogenous alpha1, 3
      galactosyltransferase enzyme activity.

PMID- 9632708
TI  - Di-leucine-mediated internalization of ligand by a truncated growth hormone
      receptor is independent of the ubiquitin conjugation system.
AB  - The growth hormone receptor (GHR) is a member of the cytokine receptor family.
      Its function is to mediate cellular responses upon binding of growth hormone.
      Ligand binding induces dimerization and activation of the GHR. One mechanism by
      which the GHR is rapidly inactivated involves the ubiquitin conjugation system, a
      system implicated in the degradation of cytosolic and nuclear proteins. We have
      shown previously that the ubiquitin-conjugating system mediates internalization
      of the GHR. Here, we present evidence that in addition to the ubiquitin-dependent
      endocytosis signal, the cytosolic tail of the GHR contains a di-leucine motif.
      Upon truncation of the GHR at amino acid residue 349, this di-leucine motif is
      activated and mediates ubiquitin-independent internalization of the receptor. Di
      leucine-mediated GHR internalization requires functional clathrin-coated pits and
      results in GHR transport to the lysosome. Although the full-length GHR
      internalizes independent of the di-leucine motif, this motif may function in
      internalization of GHR isoforms.

PMID- 9632709
TI  - Isolation and characterization of a novel coactivator protein, NCoA-62, involved
      in vitamin D-mediated transcription.
AB  - The vitamin D receptor (VDR) forms a heterodimeric complex with retinoid X
      receptor (RXR) and binds to vitamin D-responsive promoter elements to regulate
      the transcription of specific genes or gene networks. The precise mechanism of
      transcriptional regulation by the VDR.RXR heterodimer is not well understood, but
      it may involve interactions of VDR.RXR with transcriptional coactivator or
      corepressor proteins. Here, a yeast two-hybrid strategy was used to isolate
      proteins that selectively interacted with VDR and other nuclear receptors. One
      cDNA clone designated NCoA-62, encoded a 62, 000-Da protein that is highly
      related to BX42, a Drosophila melanogaster nuclear protein involved in ecdysone
      stimulated gene expression. Yeast two-hybrid studies and in vitro protein-protein
      interaction assays using glutathione S-transferase fusion proteins demonstrated
      that NCoA-62 formed a direct protein-protein contact with the ligand binding
      domain of VDR. Coexpression of NCoA-62 in a vitamin D-responsive transient gene
      expression system augmented 1, 25-dihydroxyvitamin D3-activated transcription,
      but it had little or no effect on basal transcription or gal4-VP16-activated
      transcription. NCoA-62 also interacted with retinoid receptors, and its
      expression enhanced retinoic acid-, estrogen-, and glucocorticoid-mediated gene
      expression. These data indicate that NCoA-62 may be classified into an emerging
      set of transcriptional coactivator proteins that function to facilitate vitamin D
      and other nuclear receptor-mediated transcriptional pathways.

PMID- 9632710
TI  - Identification of the CD8 DE loop as a surface functional epitope. Implications
      for major histocompatibility complex class I binding and CD8 inhibitor design.
AB  - We used an approach of protein surface epitope mapping by synthetic peptides to
      analyze the surface structure-function relationship of the CD8 protein. Small
      synthetic peptide mimics of the CD8 DE loop were shown to effectively block CD8
      binding to major histocompatibility complex (MHC) class I molecules and possess
      significant inhibitory activity on in vitro CD8(+) T cell function. These results
      suggested that the DE loop region of the CD8 protein is an important functional
      epitope mediating CD8-MHC class I interaction and the activation of CD8(+) T
      cells, a finding that is consistent with the recently reported crystal structure
      of the CD8-MHC class I complex. The structural basis for the biological activity
      of the DE loop peptide was further analyzed in a series of analogs containing
      alanine substitutions. This study provides support for the concept of bioactive
      peptide design based on protein surface epitopes and suggests that such an
      approach may be applicable to other protein-protein complexes, particularly those
      of immunoglobulin superfamily molecules.

PMID- 9632711
TI  - Activation of the heat shock factor 1 by serine protease inhibitors. An effect
      associated with nuclear factor-kappaB inhibition.
AB  - Heat shock proteins (HSPs) have a cytoprotective role in several human diseases,
      including ischemia and viral infection. Nuclear factor-kappaB (NF-kappaB) is a
      critical regulator of inflammation and virus replication. Here we report that a
      class of serine protease inhibitors with NF-kappaB-inhibitory activity are potent
      HSP inducers via activation of heat shock transcription factor 1 (HSF1) in human
      cells. 3,4-Dichloroisocoumarin, the most effective compound, rapidly induces HSF1
      DNA binding activity and phosphorylation, leading to transcription and
      translation of heat shock genes for a period of several hours. HSF1 activation is
      independent of de novo protein synthesis and is correlated in a concentration-
      and time-dependent manner with NF-kappaB inhibition. Cysteine protease inhibitors
      E64 and calpain inhibitor II, which do not block NF-kappaB activation, do not
      induce HSF DNA binding activity. HSP induction by 3,4-dichloroisocoumarin is
      associated with antiviral activity during rhabdovirus infection. These results
      identify a new class of HSP inducers and indicate a link between the regulatory
      pathways of HSF and NF-kappaB, suggesting novel strategies to simultaneously
      switch on cytoprotective genes and down-regulate inflammatory and viral genes.

PMID- 9632712
TI  - Nop5p is a small nucleolar ribonucleoprotein component required for pre-18 S rRNA
      processing in yeast.
AB  - We have identified a novel nucleolar protein, Nop5p, that is essential for growth
      in Saccharomyces cerevisiae. Monoclonal antibodies B47 and 37C12 recognize Nop5p,
      which has a predicted size of 57 kDa and possesses a KKX repeat motif at its
      carboxyl terminus. Truncations that removed the KKX motif were functional and
      localized to the nucleolus, but conferred slow growth at 37 degreesC. Nop5p shows
      significant sequence homology with yeast Sik1p/Nop56p, and putative homologues in
      archaebacteria, plants, and human. Depletion of Nop5p in a GAL-NOP5 strain
      lengthened the doubling time about 5-fold, and selectively reduced steady-state
      levels of 40 S ribosomal subunits and 18 S rRNA relative to levels of free 60 S
      subunits and 25 S rRNA. Northern blotting and primer extension analyses showed
      that Nop5p depletion impairs processing of 35 S pre-rRNA at the A0 and A2
      cleavage sites. Nop5p is associated with the small nucleolar RNAs U3, snR13, U14,
      and U18. Depletion of Nop5p caused the nucleolar protein Nop1p (yeast
      fibrillarin) to be localized to the nucleus and cytosol. Also, 37C12 co
      immunoprecipitated Nop1p. These results suggest that Nop5p functions with Nop1p
      in the execution of early pre-rRNA processing steps that lead to formation of 18
      S rRNA.

PMID- 9632713
TI  - Molecular cloning of sucrase-isomaltase cDNA in the house musk shrew Suncus
      murinus and identification of a mutation responsible for isolated sucrase
      deficiency.
AB  - Isolated sucrase deficiency has been demonstrated in a line of house musk shrew,
      Suncus murinus (laboratory name: suncus). This animal belongs to the order
      Insectivore and is phylogenetically different from ordinarily used laboratory
      animals. They are believed to have evolved with mainly animal food without
      sucrose. To study the molecular basis of the sucrase deficiency in suncus, we
      cloned 6. 0-kilobase (kb) sucrase-isomaltase (SI, EC 3.2.1.48-10) cDNA from
      suncus intestinal cDNA library. The cDNA clone contained a 5442-base pair (bp)
      long open reading frame preceded by an in frame termination codon. The deduced
      1813-amino acid sequence showed 68.6, 71.2, and 74.7% similarity with those of
      rat, rabbit, and human, respectively. A cleavage site between isomaltase and
      sucrase as well as the region surrounding the catalytic sites for sucrase and
      isomaltase were conserved among the species. Out of 18 potential N-linked
      glycosylation sites, 5 were common among all 4 species. In the connecting segment
      which was enriched with O-linked glycosylation sites in the other species, only
      two sites were present in suncus. Northern blot analysis revealed that the 6.0-kb
      SI mRNA was expressed in the KAT line with intact sucrase-isomaltase activity. In
      contrast, 3.0-kb SI mRNA was expressed in suncus of the MI line with isolated
      sucrase deficiency. The 3.0-kb mRNA cosegregated with sucrase deficiency
      phenotype as an autosomal recessive trait. Sequence analysis revealed a 2
      nucleotide deletion at position 2767-2768, which results in a frameshift and an
      immature termination codon. The cDNA of the MI line diverged from that of the KAT
      line at position 2865, having an 18-bp unique sequence followed by a poly(A)
      tail. The mutant cDNA encodes 922 amino acid residues which preserves the region
      for isomaltase but lacks that for whole sucrase. While the cells transfected with
      the plasmids expressing SI in the KAT line showed both sucrase and isomaltase
      activity, the plasmids expressing MI line cDNA showed only isomaltase activity.
      Thus it was concluded that the mutation in the SI gene was responsible for
      isolated sucrase deficiency in the MI line.

PMID- 9632714
TI  - The presenilin 1 protein is a component of a high molecular weight intracellular
      complex that contains beta-catenin.
AB  - The presenilin (PS) genes associated with Alzheimer disease encode polytopic
      transmembrane proteins which undergo physiologic endoproteolytic cleavage to
      generate stable NH2- and COOH-terminal fragments (NTF or CTF) which co-localize
      in intracellular membranes, but are tightly regulated in their stoichiometry and
      abundance. We have used linear glycerol velocity and discontinuous sucrose
      gradient analysis to investigate the distribution and native conformation of PS1
      and PS2 during this regulated processing in cultured cells and in brain. The PS1
      NTF and CTF co-localize in the endoplasmic reticulum (ER) and in the Golgi
      apparatus, where they are components of a approximately 250-kDa complex. This
      complex also contains beta-catenin but not beta-amyloid precursor protein (APP).
      In contrast, the PS1 holoprotein precursor is predominantly localized to the
      rough ER and smooth ER, where it is a component of a approximately 180-kDa native
      complex. PS2 forms similar but independent complexes. Restricted incorporation of
      the presenilin NTF and CTF along with a potentially functional ligand (beta
      catenin) into a multimeric complex in the ER and Golgi apparatus may provide an
      explanation for the regulated accumulation of the NTF and CTF.

PMID- 9632715
TI  - The reduced levels of chi recognition exhibited by the RecBC1004D enzyme reflect
      its recombination defect in vivo.
AB  - Homologous recombination in Escherichia coli is initiated by the RecBCD enzyme
      and is stimulated by an 8-nucleotide element known as Chi (chi). We present a
      detailed biochemical characterization of a mutant RecBCD enzyme, designated
      RecBC1004D, that displays a reduced level of chi site recognition. Initially
      characterized genetically as unable to respond to the chi sequence, we provide
      evidence to indicate that the ability of this mutant enzyme to respond to chi is
      reduced rather than lost; the mutant displays about 20-fold lower chi recognition
      than wild-type RecBCD enzyme. Although this enzyme exhibits wild-type levels of
      double-stranded DNA exonuclease, helicase, and ATPase activity, its ability to
      degrade single-stranded DNA is enhanced 2-3-fold. The data presented here suggest
      that the reduced recombination proficiency of the recBC1004D strain observed in
      vivo results from a basal level of modification of the RecBC1004D enzyme at both
      chi-specific, as well as nonspecific, DNA sequences.

PMID- 9632716
TI  - Conditional, tissue-specific expression of Q205L Galphai2 in vivo mimics insulin
      activation of c-Jun N-terminal kinase and p38 kinase.
AB  - Deficiency of the G-protein subunit Galphai2 impairs insulin action (Moxham, C.
      M., and Malbon, C. C. (1996) Nature 379, 840-844). By using the promoter for the
      phosphoenolpyruvate carboxykinase gene, conditional, tissue-specific expression
      of the constitutively active mutant form (Q205L) of Galphai2 was achieved in mice
      harboring the transgene. Expression of Q205L Galphai2 was detected in skeletal
      muscle, liver, and adipose tissue of transgenic mice. Whereas the Galphai2
      deficient mice displayed blunted insulin action, the Q205L Galphai2-expressing
      mice displayed enhanced insulin-like effects. Glycogen synthase in skeletal
      muscle was found to be activated in Q205L Galphai2-expressing mice, in the
      absence of the administration of insulin. Analysis of members of mitogen
      activated protein kinase family revealed that both c-Jun N-terminal kinase and
      p38 are constitutively activated in vivo in the mice that express the Q205L
      Galphai2. ERK1,2, in contrast, are unaffected in the Q205L Galphai2-expressing
      mice. Insulin, like expression of Q205L Galphai2, activates both p38 and c-Jun N
      terminal kinases as well as glycogen synthase. Activation of c-Jun N-terminal and
      p38 kinases in vivo with anisomycin, however, was insufficient to activate
      glycogen synthase. Much like Galphai2 deficiency provokes insulin resistance,
      expression of Q205L constitutively active Galphai2 mimics insulin action in vivo,
      sharing with insulin the activation of two mitogen-activated protein kinase
      members, p38 and c-Jun N-terminal kinases.

PMID- 9632717
TI  - Transcription factor E2F and cyclin E-Cdk2 complex cooperate to induce
      chromosomal DNA replication in Xenopus oocytes.
AB  - Although no chromosomal DNA replication actually occurs during Xenopus oocyte
      maturation, the capability develops during the late meiosis I (MI) phase in
      response to progesterone. This ability, however, is suppressed by Mos proteins
      and maturation/mitosis promoting factor during the second meiosis phase (meiosis
      II; MII) until fertilization. Inhibition of RNA synthesis by actinomycin D during
      early MI prevented induction of the replication ability, but did not interfere
      with initiation of the meiotic cell cycle progression characterized by
      oscillation of the maturation/mitosis promoting factor activity and germinal
      vesicle breakdown. Microinjection of recombinant proteins such as dominant
      negative E2F or universal Cdk inhibitors, p21 and p27, but not wild type human
      E2F-1 or Cdk4-specific inhibitor, p19, into maturing oocytes during MI abolished
      induction of the DNA replication ability. Co-injection of human E2F-1 and cyclin
      E proteins into immature oocytes allowed them to initiate DNA replication even in
      the absence of progesterone treatment. Injection of cyclin E alone, which was
      sufficient to activate endogenous Cdk2 kinase, failed to induce DNA replication.
      Moreover, the activation of Cdk2 was not affected under the conditions where DNA
      replication was blocked by actinomycin D. Thus, like somatic cells, both
      activities of E2F and cyclin E-Cdk2 complex are required for induction of the DNA
      replication ability in maturing Xenopus oocytes, and enhancement of both
      activities enables oocytes to override DNA-replication inhibitory mechanisms that
      specifically lie in maturing oocytes.

PMID- 9632719
TI  - Recruitment of human TBP selectively activates RNA polymerase II TATA-dependent
      promoters.
AB  - An increasing body of evidence suggests that eukaryotic activators stimulate
      polymerase II transcription by facilitating the assembly of the functional basal
      machinery at the promoter. Here we describe experiments that provide added
      support for the idea that recruitment of TATA-binding protein (TBP) is a rate
      limiting step for transcription activation in mammalian cells. We found that, in
      human cell lines, recruitment of TBP to a promoter, as a GAL4-TBP fusion protein,
      can provide a substantial activation of transcription. Activation mediated by the
      hTBP, tethered to promoter DNA, is strictly dependent upon the presence of a
      functional TATA element, and it directs faithful transcription initiation.
      Interestingly, GAL4-hTBP activation was not observed from initiator (Inr) 
      dependent TATA-less promoters. These results suggest that TBP binding to DNA is
      not a rate-limiting step for the initial stages of TFIID recruitment to initiator
      dependent TATA-less promoters. Finally, we provide evidence that synergy between
      GAL4-hTBP and defined transcription domains is restricted to activators, such as
      VP16 and Tat, which are likely to function at steps subsequent to the TFIID
      recruitment. These findings strengthen the idea that recruitment of TBP
      represents an important mechanism of activation of TATA-dependent promoters, and
      on the other hand, they suggest that TBP-DNA interactions are largely dispensable
      for specific transcription of initiator dependent TATA-less promoters.

PMID- 9632718
TI  - Loss of AP-2 results in up-regulation of MCAM/MUC18 and an increase in tumor
      growth and metastasis of human melanoma cells.
AB  - MCAM/MUC18 is a cell-surface glycoprotein of 113 kDa, originally identified as a
      melanoma antigen, whose expression is associated with tumor progression and the
      development of metastatic potential. We have previously shown that enforced
      expression of MCAM/MUC18 in primary cutaneous melanoma led to increased tumor
      growth and metastatic potential in nude mice. The mechanism for up-regulation of
      MCAM/MUC18 during melanoma progression is unknown. Here we show that up
      regulation of MCAM/MUC18 expression in highly metastatic cells correlates with
      loss of expression of the transcription factor AP-2. The MCAM/MUC18 promoter
      contains four binding sites for AP-2, and electrophoretic mobility shift assay
      gels demonstrated that the AP-2 protein bound directly to the MCAM/MUC18
      promoter. Transfection of AP-2 into highly metastatic A375SM melanoma cells (AP-2
      negative and MCAM/MUC18-positive) inhibited MCAM/MUC18 promoter-driven
      chloramphenicol acetyltransferase reporter gene in a dose-dependent manner.
      MCAM/MUC18 mRNA and protein expression were down-regulated in AP-2-transfected
      but not in control cells. In addition, re-expression of AP-2 in A375SM cells
      inhibited their tumorigenicity and metastatic potential in nude mice. These
      results indicate that the expression of MCAM/MUC18 is regulated by AP-2 and that
      enforced AP-2 expression suppresses tumorigenicity and metastatic potential of
      human melanoma cells, possibly by down-regulating MCAM/MUC18 gene expression.
      Since AP-2 also regulates other genes that are involved in the progression of
      human melanoma such as c-KIT, E-cadherin, MMP-2, and p21(WAF-1), we propose that
      loss of AP-2 is a crucial event in the development of malignant melanoma.

PMID- 9632720
TI  - The unmethylated state of CpG islands in mouse fibroblasts depends on the
      poly(ADP-ribosyl)ation process.
AB  - In vivo and in vitro experiments carried out on L929 mouse fibroblasts suggested
      that the poly(ADP-ribosyl) ation process acts somehow as a protecting agent
      against full methylation of CpG dinucleotides in genomic DNA. Since CpG islands,
      which are found almost exclusively at the 5'-end of housekeeping genes, are rich
      in CpG dinucleotides, which are the target of mammalian DNA methyltransferase, we
      examined the possibility that the poly(ADP-ribosyl)ation reaction is involved in
      maintaining the unmethylated state of these DNA sequences. Experiments were
      conducted by two different strategies, using either methylation-dependent
      restriction enzymes on purified genomic DNA or a sequence-dependent restriction
      enzyme on an aliquot of the same DNA, previously modified by a bisulfite
      reaction. With the methylation-dependent restriction enzymes, it was observed
      that the "HpaII tiny fragments" greatly decreased when the cells were
      preincubated with 3-aminobenzamide, a well known inhibitor of poly(ADP-ribose)
      polymerase. The other experimental approach allowed us to prove that, as a
      consequence of the inhibition of the poly(ADP-ribosyl)ation process, an anomalous
      methylation pattern could be evidenced in the CpG island of the promoter fragment
      of the Htf9 gene, amplified from DNA obtained from fibroblasts preincubated with
      3-aminobenzamide. These data confirm the hypothesis that, at least for the Htf9
      promoter region, an active poly(ADP-ribosyl)ation protects the unmethylated state
      of the CpG island.

PMID- 9632721
TI  - Involvement of de novo ceramide biosynthesis in tumor necrosis factor
      alpha/cycloheximide-induced cerebral endothelial cell death.
AB  - Cytokines, including tumor necrosis factor-alpha (TNF-alpha), may elicit
      cytotoxic response through the sphingomyelin-ceramide signal transduction pathway
      by activation of sphingomyelinases and the subsequent release of ceramide: the
      universal lipid second messenger. Treatment of bovine cerebral endothelial cells
      (BCECs) with TNF-alpha for 16 h followed by cycloheximide (CHX) for 6 h resulted
      in an increase in ceramide accumulation, DNA fragmentation, and cell death.
      Application of a cell permeable ceramide analogue C2 ceramide, but not the
      biologically inactive C2 dihydroceramide, also induced DNA laddering and BCEC
      death in a concentration- and time-dependent manner. TNF-alpha/CHX-mediated
      ceramide production apparently is not a result of sphingomyelin hydrolysis
      because sphingomyelin content does not decrease in this death paradigm. In
      addition, an acidic sphingomyelinase inhibitor, desipramine, had no effect on TNF
      alpha/CHX-induced cell death. However, addition of fumonisin B1, a selective
      ceramide synthase inhibitor, attenuated TNF-alpha/CHX-induced intracellular
      ceramide elevation and BCEC death. Together, these findings suggest that ceramide
      plays at least a partial role in this paradigm of BCEC death. Our results show,
      for the first time, that ceramide derived from de novo synthesis is an
      alternative mechanism to sphingomyelin hydrolysis in the BCEC death process
      initiated by TNF-alpha/CHX.

PMID- 9632722
TI  - Induction of transforming growth factor-beta receptor type II expression in
      estrogen receptor-positive breast cancer cells through SP1 activation by 5-aza-2'
      deoxycytidine.
AB  - Previous studies suggest that estrogen receptor-positive (ER+) breast cancer
      cells acquire resistance to transforming growth factor-beta (TGF-beta) because of
      reduced expression levels of TGF-beta receptor type II (RII). We now report that
      treatment of ER+ breast cancer cells with the DNA methyltransferase inhibitor 5
      aza-2'-deoxycytidine (5-aza-2'-dC) leads to accumulation of RII transcript and
      protein in three different cell lines. RII induction restored TGF-beta response
      in MCF-7L breast cancer cells as indicated by the enhanced activity of a TGF-beta
      responsive promoter-reporter construct (p3TP-Lux). A transiently transfected RII
      promoter-reporter element (RII-chloramphenicol acetyltransferase) showed an
      increase in activity in the 5-aza-2'-dC-treated MCF-7L cells compared with
      untreated cells, suggesting the activation of a transactivator of RII
      transcription. Using electrophoretic mobility shift assays, the enhanced binding
      of proteins from 5-aza-2'-dC-treated MCF-7L nuclear extracts to radiolabeled Sp1
      oligonucleotides was demonstrated. An RII promoter-chloramphenicol
      acetyltransferase construct containing a mutation in the Sp1 site was not
      expressed in the 5-aza-2'-dC-treated MCF-7L cells, further demonstrating that
      induction of Sp1 activity by 5-aza-2'-dC in the MCF-7L cells was critical to RII
      expression. Northern analysis indicated that 5-aza-2'-dC treatment did not affect
      the Sp1 transcript levels. Western blot analysis revealed an increase of Sp1
      protein in the 5-aza-2'-dC-treated MCF-7L cells, but there was no change in the c
      Jun levels. Studies after cyclohexamide treatment suggested an increase in the
      Sp1 protein stability from the 5-aza-2'-dC-treated MCF-7L extracts compared with
      untreated control extracts. These results indicate that the transcriptional
      repression of RII in the ER+ breast cancer cells is caused by suboptimal activity
      of Sp1, whereas treatment with 5-aza-2'-dC stabilizes the protein thus increasing
      steady-state Sp1 levels and thereby leads to enhanced RII transcription and
      subsequent restoration of TGF-beta sensitivity.

PMID- 9632723
TI  - KID-1, a protein kinase induced by depolarization in brain.
AB  - Membrane depolarization leads to changes in gene expression that modulate
      neuronal plasticity. Using representational difference analysis, we have
      identified a previously undiscovered cDNA, KID-1 (kinase induced by
      depolarization), that is induced by membrane depolarization or forskolin, but not
      by neurotrophins or growth factors, in PC12 pheochromocytoma cells. KID-1 is an
      immediate early gene that shares a high degree of sequence similarity with the
      family of PIM-1 serine/threonine protein kinases. Recombinant KID-1 fusion
      protein is able to catalyze both histone phosphorylation and autophosphorylation.
      KID-1 mRNA is present in a number of unstimulated tissues, including brain. In
      response to kainic acid and electroconvulsive shock-induced seizures, KID-1 is
      induced in specific regions of the hippocampus and cortex.

PMID- 9632724
TI  - Critical role for the 310 helix region of p57(Kip2) in cyclin-dependent kinase 2
      inhibition and growth suppression.
AB  - Although crystal structural analysis of cyclin A/cyclin-dependent kinase 2
      (Cdk2)/p27 (Russo, A. A., Jeffrey, P. D., Pattern, A. K., Massague, J., and
      Pavletich, N. P. (1996) Nature 382, 325-331) has suggested that the 310 helix
      region in Cdk inhibitors of the Cip/Kip family may be involved in the inhibition
      of cyclin/Cdk activities, there is no biochemical evidence supporting this
      hypothesis. In the present study, we demonstrated that cyclin and Cdk binding
      domains of p57 were necessary but were not sufficient in themselves for the
      inhibition of cyclin A/Cdk2 and cyclin E/Cdk2, and that the 3(10) helix region of
      this protein is indispensable for the inhibition of these complexes. In contrast,
      the 3(10) helix regions of p21 and p27 were not required, and cyclin- and Cdk
      binding domains alone were sufficient for the inhibition of all cyclin/Cdk
      complexes examined. Site-directed mutagenesis identified phenylalanine 79 and
      tyrosine 80 within the 3(10) helix region of p57 as crucial residues for kinase
      inhibition, supporting the structural evidence that the 3(10) helix binds deep
      inside the catalytic cleft of Cdk2, mimicking ATP. Mutations within the 3(10)
      helix region of the p57 molecule completely abolished the ability to arrest the
      cell cycle at G1 in vivo. These results indicate that this region is specifically
      utilized by p57 in selectively inhibiting cyclin A or E/Cdk2+ activities. Thus
      the 3(10) helix motif may confer a specific regulatory mechanism by which p57
      differentially regulates Cdk2 and Cdk4 activities.

PMID- 9632725
TI  - Identification of single C motif-1/lymphotactin receptor XCR1.
AB  - Single C motif-1 (SCM-1)/lymphotactin is a member of the chemokine superfamily,
      but retains only the 2nd and 4th of the four cysteine residues conserved in other
      chemokines. In humans, there are two highly homologous SCM-1 genes encoding SCM
      1alpha and SCM-1beta with two amino acid substitutions. To identify a specific
      receptor for SCM-1 proteins, we produced recombinant SCM-1alpha and SCM-1beta by
      the baculovirus expression system and tested them on murine L1.2 cells stably
      expressing eight known chemokine receptors and three orphan receptors. Both
      proteins specifically induced migration in cells expressing an orphan receptor,
      GPR5. The migration was chemotactic and suppressed by pertussis toxin, indicating
      coupling to a Galpha type of G protein. Both proteins also induced intracellular
      calcium mobilization in GPR5-expressing L1.2 cells with efficient mutual cross
      desensitization. SCM-1alpha bound specifically to GPR5-expressing L1.2 cells with
      a Kd of 10 nM. By Northern blot analysis, GPR5 mRNA of about 5 kilobases was
      detected strongly in placenta and weakly in spleen and thymus among various human
      tissues. Identification of a specific receptor for SCM-1 would facilitate our
      investigation on its biological function. Following the set rule for the
      chemokine receptor nomenclature, we propose to designate GPR5 as XCR1 from XC
      chemokine receptor-1.

PMID- 9632726
TI  - Thiamin biosynthesis in Escherichia coli. Identification of ThiS thiocarboxylate
      as the immediate sulfur donor in the thiazole formation.
AB  - ThiFSGH and ThiI are required for the biosynthesis of the thiazole moiety of
      thiamin in Escherichia coli. The overproduction, purification, and
      characterization of ThiFS and the identification of two of the early steps in the
      biosynthesis of the thiazole moiety of thiamin are described here. ThiS isolated
      from E. coli thiI+ is post-translationally modified by converting the carboxylic
      acid group of the carboxyl-terminal glycine into a thiocarboxylate. The thiI gene
      plays an essential role in the formation of the thiocarboxylate because ThiS
      isolated from a thiI- strain does not contain this modification. ThiF catalyzes
      the adenylation by ATP of the carboxyl-terminal glycine of ThiS. This reaction is
      likely to be involved in the activation of ThiS for sulfur transfer from cysteine
      or from a cysteine-derived sulfur donor.

PMID- 9632727
TI  - Structure-function relationships and localization of the Na/Ca-K exchanger in rod
      photoreceptors.
AB  - The structural and functional properties of the bovine rod photoreceptor Na/Ca-K
      exchanger and its distribution in vertebrate photoreceptor cells were studied
      using a panel of monoclonal antibodies. Antibodies that bind to distinct epitopes
      along the large hydrophilic N-terminal segment of the exchanger labeled the
      extracellular surface of the rod outer segment plasma membrane, whereas
      antibodies against a large hydrophilic loop between the two membrane domains
      labeled the intracellular side. Enzymatic deglycosylation studies indicated that
      the exchanger primarily contains O-linked sialo-oligosaccharides located within
      the N-terminal domain. Removal of the extracellular domain with trypsin or the
      large intracellular domain with kallikrein did not alter the Na+- or K+-dependent
      Ca2+ efflux activity of the exchanger when reconstituted into lipid vesicles.
      Anti-exchanger antibodies were also used to visualize the distribution of the
      exchanger in the retina by light and electron microscopy. The exchanger was
      localized to the plasma membrane of rod outer segments. No labeling was observed
      in the disk membranes, cone photoreceptor cells, or other retinal neurons, and
      only faint staining was seen in the rod inner segment. These results indicate
      that the O-linked glycosylated rod Na/Ca-K exchanger is specifically targeted to
      the plasma membrane of rod photoreceptors and has a topological organization
      similar to that reported for the cardiac Na/Ca exchanger. The large intracellular
      and extracellular domains do not directly function in the transport of ions
      across the rod outer segment plasma membrane, but instead may play a role in
      protein-protein interactions that maintain the spatial organization of the
      exchanger in the plasma membrane or possibly regulate transport activity of the
      exchanger.

PMID- 9632728
TI  - Inhibition of Akt kinase by cell-permeable ceramide and its implications for
      ceramide-induced apoptosis.
AB  - Ceramide is an important lipid messenger involved in mediating a variety of cell
      functions including apoptosis. However, mechanisms responsible for ceramide
      induced apoptosis remain unclear. We investigated the possibility that ceramide
      may decrease antiapoptotic signaling in cells by inhibiting Akt kinase activity.
      Our data show that C2-ceramide induces apoptosis in HMN1 motor neuron cells and
      decreases both basal and insulin- or serum-stimulated Akt kinase activity 65-70%.
      These results are consistent with decreased Akt kinase activity being involved in
      the apoptotic effects of ceramide. This possibility is further supported by
      studies showing that constitutively active Akt kinase decreases C2-ceramide
      induced death of HMN1 cells as well as COS-7 cells. Decreased Akt activity is not
      due to ceramide activating the ceramide-activated protein phosphatase or to a
      direct inhibition of Akt kinase by ceramide, suggesting that ceramide acts
      upstream of Akt kinase to decrease its activity. Treating cells with C2-ceramide
      does not affect phosphorylation of insulin receptor substrate-1, interactions
      between insulin receptor substrate-1 and p85, or insulin-stimulated
      phosphatidylinositol 3-kinase activity, suggesting that the effects of C2
      ceramide on Akt kinase are not mediated through modulating phosphatidylinositol 3
      kinase. In sum, our results suggest that inhibition of the key antiapoptotic
      kinase, Akt, may play an important role in ceramide-induced apoptosis.

PMID- 9632729
TI  - Modulation of secreted beta-amyloid precursor protein and amyloid beta-peptide in
      brain by cholesterol.
AB  - The effects of dietary cholesterol on brain amyloid precursor protein (APP)
      processing were examined using an APP gene-targeted mouse, genetically humanized
      in the amyloid beta-peptide (Abeta) domain and expressing the Swedish familial
      Alzheimer's disease mutations. These mice express endogenous levels of APP
      holoprotein and abundant human Abeta. Increased dietary cholesterol led to
      significant reductions in brain levels of secreted APP derivatives, including
      sAPPalpha, sAPPbeta, Abeta1-40, and Abeta1-42, while having little to no effect
      on cell-associated species, including full-length APP and the COOH-terminal APP
      processing derivatives. The changes in levels of sAPP and Abeta in brain all were
      negatively correlated with serum cholesterol levels and levels of serum and brain
      apoE. These results demonstrate that secreted APP processing derivatives and
      Abeta can be modulated in the brain of an animal by diet and provide evidence
      that cholesterol plays a role in the modulation of APP processing in vivo. APP
      gene-targeted mice lacking apoE, also have high serum cholesterol levels but do
      not show alterations in APP processing, suggesting that effects of cholesterol on
      APP processing require the presence of apoE.

PMID- 9632730
TI  - The hydrophilic domain of Tic110, an inner envelope membrane component of the
      chloroplastic protein translocation apparatus, faces the stromal compartment.
AB  - It has previously been found that Tic110, an integral protein of the chloroplast
      inner envelope membrane, is a component of the chloroplastic protein import
      apparatus. However, conflicting reports exist concerning the topology of this
      protein within the inner envelope membrane. In this report, we provide evidence
      that indicates that the large (>90-kDa) hydrophilic domain of Tic110 is localized
      within the chloroplast stroma. Trypsin, a protease that cannot penetrate the
      permeability barrier of the inner envelope membrane, degrades neither Tic110 nor
      other proteins exposed to the stromal compartment but is able to digest proteins
      exposed to the intermembrane space between the two envelope membranes. Previous
      reports indicating that trypsin is able to degrade Tic110 were influenced by
      incomplete quenching of protease activity. When trypsin is not sufficiently
      quenched, it is able to digest Tic110, but only after chloroplasts have been
      ruptured. It is therefore necessary to employ adequate quenching protocols, such
      as the one reported here, whenever trypsin is utilized as an analytical tool.
      Based on a stromal localization for the majority of Tic110, we propose that this
      protein may be involved in the recruitment of stromal factors, possibly molecular
      chaperones, to the translocation apparatus during protein import.

PMID- 9632731
TI  - Apoptosis induction by caspase-8 is amplified through the mitochondrial release
      of cytochrome c.
AB  - Apoptosis often involves the release of cytochrome c from mitochondria, leading
      to caspase activation. However, in apoptosis mediated by CD95 (Fas/APO-1),
      caspase-8 (FLICE/MACH/Mch5) is immediately activated and, in principle, could
      process other caspases directly. To investigate whether caspase-8 could also act
      through mitochondria, we added active caspase-8 to a Xenopus cell-free system
      requiring these organelles. Caspase-8 rapidly promoted the apoptotic program,
      culminating in fragmentation of chromatin and the nuclear membrane. In extracts
      devoid of mitochondria, caspase-8 produced DNA degradation, but left nuclear
      membranes intact. Thus, mitochondria were required for complete engagement of the
      apoptotic machinery. In the absence of mitochondria, high concentrations of
      caspase-8 were required to activate downstream caspases. However, when
      mitochondria were present, the effects of low concentrations of caspase-8 were
      vastly amplified through cytochrome c-dependent caspase activation. Caspase-8
      promoted cytochrome c release indirectly, by cleaving at least one cytosolic
      substrate. Bcl-2 blocked apoptosis only at the lowest caspase-8 concentrations,
      potentially explaining why CD95-induced apoptosis can often evade inhibition by
      Bcl-2.

PMID- 9632732
TI  - Dual regulation of stromelysin-3 by fibroblast growth factor-2 in murine
      osteoblasts.
AB  - Osteoblasts express stromelysin-3, a matrix metalloproteinase associated with
      normal remodeling processes and with stromal fibroblasts surrounding many
      invasive carcinomas. Fibroblast growth factors (FGFs) play an important role in
      skeletal development, fracture repair, and osteoblast function. The osteoblastic
      cell line MC3T3 was used to study the regulation of stromelysin-3 by FGF-2.
      Acutely, FGF-2 decreased stromelysin-3 mRNA levels, whereas prolonged treatment
      caused an induction of stromelysin-3 mRNA. RNA stability studies and nuclear run
      off assays indicated that acute treatment with FGF-2 decreased stromelysin-3 mRNA
      stability but did not alter gene transcription. However, the induction of
      stromelysin-3 after prolonged treatment with FGF-2 resulted from increased gene
      transcription, with no effect on RNA stability. The stimulatory effect was
      protein synthesis-dependent, whereas the inhibitory effect was not. This study
      demonstrates dual regulation of stromelysin-3 by FGF-2: acute destabilization of
      stromelysin-3 mRNA, followed by induction of gene transcription. This complex
      regulation may be important in the function of stromelysin-3 in bone and in
      remodeling processes, such as wound and fracture repair.

PMID- 9632734
TI  - Activation of extracellular signal-regulated kinase 2 by a novel Abl-binding
      protein, ST5.
AB  - The human ST5 gene encodes three proteins with predicted molecular masses of 126,
      82, and 70 kDa. These widely expressed proteins share a C-terminal region that
      bears significant sequence homology to a group of GDP/GTP exchange proteins for
      the Rab3 family of small GTP binding proteins. The N-terminal region of the
      largest ST5 protein, p126, contains two proline-rich sequences, PR1 and PR2, with
      consensus motifs similar to Src homology 3 (SH3) binding regions and to mitogen
      activated protein kinase (MAPK) phosphorylation sites. Based on these properties,
      we sought to investigate the activity of ST5 proteins in signal transduction
      pathways. In vitro, p126 displayed preferential binding to c-Abl SH3, as compared
      with other SH3 domains. This interaction was mediated by the PR2 sequence. In
      vivo, expression of p126, but not p82 or p70, activated MAPK/ERK2 in response to
      EGF in COS-7 cells. Expression of c-Abl with p126 greatly enhanced this activity.
      Deletion of PR1 blocked the ability of p126 to activate ERK2. Deletion of PR2 did
      not affect the basal activity, but blocked the stimulatory effect of c-Abl.
      Whereas p82 expression had no effect on ERK2 activation by p126, p70 completely
      abrogated this activity. These observations suggest that ST5 can function as a
      signaling protein and can provide a link between c-Abl and ERK2.

PMID- 9632733
TI  - Phosphorylation of PITSLRE p110 isoforms accompanies their processing by caspases
      during Fas-mediated cell death.
AB  - A number of cellular proteins have been identified as caspase targets during cell
      death, including the PITSLRE protein kinases. These targets generally fall into
      one of three possible categories: 1) other caspases, 2) proteins that are
      inactivated during apoptosis, and 3) proteins that are required for execution of
      the cell death program. However, not all proteins are cleaved by caspases during
      apoptosis. Why only specific proteins are destined to be processed by caspases
      during cell death is currently not clear. Here we show that multiple caspase-like
      activities are involved in the processing of the PITSLRE p110 isoforms during Fas
      induced apoptosis in Jurkat T-cells. Three p110 caspase cleavage sites have been
      mapped to the amino-terminal domain of p110 and verified by site-directed
      mutagenesis. Curiously, the mutagenesis studies revealed that cleavage of two
      juxtaposed caspase sites is necessary for the complete processing of this protein
      during cell death in vivo. Finally, we demonstrate that the PITSLRE p110 protein
      is rapidly phosphorylated during Fas-induced apoptosis in Jurkat cells and that
      phosphorylation of an amino-terminal portion of the protein may enhance caspase
      cleavage in this region.

PMID- 9632735
TI  - TorD, a cytoplasmic chaperone that interacts with the unfolded trimethylamine N
      oxide reductase enzyme (TorA) in Escherichia coli.
AB  - Reduction of trimethylamine N-oxide (TMAO) in Escherichia coli involves the
      terminal molybdoreductase TorA, located in the periplasm, and the membrane
      anchored c type cytochrome TorC. In this study, the role of the TorD protein,
      encoded by the third gene of torCAD operon, is investigated. Construction of a
      mutant, in which the torD gene is interrupted, showed that the absence of TorD
      protein leads to a two times decrease of the final amount of TorA enzyme.
      However, specific activity and biochemical properties of TorA enzyme were similar
      to those of the enzyme produced in the wild type. Excess of TorD protein restores
      the normal level of TorA enzyme, and also, leads to the appearance of a new
      cytoplasmic form of TorA on SDS-polyacrylamide gel electrophoresis using gentle
      conditions. This probably indicates a new folding state of the cytoplasmic TorA
      protein when TorD is overexpressed. BIAcore techniques demonstrated direct
      specific interaction between the TorA and TorD proteins. This interaction was
      enhanced when TorA was previously unfolded by heating. Finally, as TorA is a
      molybdoenzyme, we demonstrated that TorD can interact with TorA before the
      molybdenum cofactor has been inserted. As TorD homologue encoding genes are found
      in various TMAO reductase loci, we propose that TorD is a chaperone protein
      specific for the TorA enzyme. It belongs to a family of TorD-like chaperones
      present in several bacteria, and, probably, involved in TMAO reductase folding.

PMID- 9632736
TI  - Regulation of the p70 S6 kinase by phosphorylation in vivo. Analysis using site
      specific anti-phosphopeptide antibodies.
AB  - The p70 S6 kinase is activated by diverse stimuli through a multisite
      phosphorylation directed at three separate domains as follows: a cluster of
      (Ser/Thr) Pro sites in an autoinhibitory segment in the noncatalytic carboxyl
      terminal tail; Thr-252 in the activation loop of the catalytic domain; and Ser
      394 and Thr-412 in a segment immediately carboxyl-terminal to the catalytic
      domain. Phosphorylation of Thr-252 in vitro by the enzyme phosphatidylinositol 3
      phosphate-dependent kinase-1 or mutation of Thr-412 --> Glu has each been shown
      previously to engender some activation of the p70 S6 kinase, whereas both
      modifications together produce 20-30-fold more activity than either alone. We
      employed phospho-specific anti-peptide antibodies to examine the relative
      phosphorylation at several of these sites in wild type and various p70 mutants,
      in serum-deprived cells, and in response to activators and inhibitors of p70 S6
      kinase activity. Substantial phosphorylation of p70 Thr-252 and Ser-434 was
      present in serum-deprived cells, whereas Thr-412 and Thr-444/Ser-447 were
      essentially devoid of phospho-specific immunoreactivity. Activation of p70 by
      insulin was accompanied by a coordinate increase in phosphorylation at all sites
      examined, together with a slowing in mobility on SDS-PAGE of a portion of p70
      polypeptides. Upon addition of rapamycin or wortmannin to insulin-treated cells,
      the decrease in activity of p70 was closely correlated with the disappearance of
      anti-Thr-412(P) immunoreactivity and the most slowly migrating p70 polypeptides,
      whereas considerable phosphorylation at Ser-434 and Thr-252 persisted after the
      disappearance of 40 S kinase activity. The central role of Thr-412
      phosphorylation in the regulation of kinase activity was further demonstrated by
      the close correlation of the effects of various deletions and point mutations on
      p70 activity and Thr-412 phosphorylation. In conclusion, although p70 activity
      depends on a disinhibition from the carboxyl-terminal tail and the simultaneous
      phosphorylation at both Thr-252 and Thr-412, p70 activity in vivo is most closely
      related to the state of phosphorylation at Thr-412.

PMID- 9632737
TI  - NADPH diaphorase histochemistry detects inducible nitric oxide synthetase
      activity in the thymus of naive and staphylococcal enterotoxin B-stimulated mice.
AB  - Here we examined the changes in NADPH diaphorase (NADPHd) and inducible nitric
      oxide synthetase (iNOS) positivity in the medulla of the mouse thymus in response
      to treatment with the superantigen, Staphylococcal enterotoxin B (SEB). A few
      NADPHd+ and iNOS+ cells scattered in the medulla were detected in the thymi of
      naive mice. SEB induced the appearance of a large number of NADPHd+- and iNOS
      immunoreactive cells in the thymic medulla. In the thymus of iNOS-deficient mice,
      a total absence of these NADPHd+ and iNOS+ medullary cells was found both under
      basal conditions and after SEB stimulation. With the NADPHd reaction, only
      endothelial staining was detected in the thymi of iNOS-deficient mice. Our data
      indicate that NADPHd+ cells in the thymic medulla express iNOS and that SEB
      induces iNOS expression in the mouse thymus.

PMID- 9632738
TI  - Histochemical reactivity of normal, metaplastic, and neoplastic tissues to alpha
      linked N-acetylglucosamine residue-specific monoclonal antibody HIK1083.
AB  - Monoclonal antibody (MAb) HIK1083, which is obtained by immunizing mice with a
      preparation of rat gastric mucins, has been shown to bind specifically to alpha
      linked N-acetylglucosamine (alpha-GlcNAc). We investigated the specificity of MAb
      HIK1083 by immunostaining normal human organs, mucinous metaplasia of human
      pancreas, adenocarcinomas of human stomach, pancreas, and colon, and normal rat
      organs. The specificity was investigated by making comparisons with (a) a stain
      that labels Class III concanavalin A (ConA)-reactive mucin (Class III mucin),
      i.e., paradoxical ConA (PCS), and (b) staining with horseradish peroxidase (HRP)
      conjugated Griffonia simplicifolia agglutinin II (GSA-II). In normal human and
      rat organs and in mucinous metaplasia of human pancreas, immunostaining with MAb
      HIK1083 and PCS showed similar specificities for mucins in glandular mucous
      cells. In adenocarcinoma of stomach and pancreas, GSA-II showed the most
      widespread positivity, PCS showed the least, and MAb HIK1083 showed a reactivity
      between those two extremes. Colon adenocarcinomas were labeled only with GSA-II.
      These results demonstrate that MAb HIK1083 could be a useful screening tool for
      Class III mucin in normal, metaplastic, and carcinoma tissues, and that the alpha
      GlcNAc residue is one of the specific sugar residues found in Class III mucin.

PMID- 9632739
TI  - Distribution of integrins during human fetal lung development.
AB  - Interactions between epithelial cells and the extracellular matrix through
      integrins play a key role in the development of the lung by modulating branching
      morphogenesis, epithelial cell polarization, and differentiation. To determine
      the role of integrins during the different stages of lung development, we
      investigated the distribution of eight integrin subunits in the trachea and lung
      from human fetuses. In distal airways, during the early pseudoglandular stage of
      development, the alpha2-, alpha5-, alpha6-, alphav-, and beta1-subunits were
      detected in all epithelial cell plasma membranes, and polarized but
      undifferentiated tracheal epithelial cells expressed alpha3-, alpha6-, and beta1
      subunits in the plasma membrane of the cells facing the basement membrane. The
      alpha6- and beta4-chains were detected along the basal plasma membrane of the
      basal cells in differentiated tracheal epithelia. The alpha4-subunit was detected
      in all respiratory cells throughout fetal development. In the submucosal glands,
      myoepithelial cells expressed the integrin subunits found in the undifferentiated
      cells of the developing airways, whereas the secretory cells expressed only
      alpha2-, alpha3-, alpha4-, alpha6-, and beta1-subunits. These results demonstrate
      differential expression of integrins during lung development and suggest that
      integrins may play multiple roles in organogenesis and maturation of respiratory
      surface epithelium and glands.

PMID- 9632740
TI  - Development and characterization of monoclonal antibodies specific to the
      serotonin 5-HT2A receptor.
AB  - Serotonin (5-hydroxytryptamine, 5-HT) mediates many functions of the central and
      peripheral nervous systems by its interaction with specific neuronal and glial
      receptors. Fourteen serotonin receptors belonging to seven families have been
      identified through physiological, pharmacological, and molecular cloning studies.
      Monoclonal antibodies (MAbs) specific for each of these receptor subtypes are
      needed to characterize their expression, distribution, and function in embryonic,
      adult, and pathological tissues. In this article we report the development and
      characterization of MAbs specific to the serotonin 5-HT2A receptor. To generate
      MAbs against 5-HT2AR, mice were immunized with the N-terminal domain of the
      receptor. The antigens were produced as glutathionine S-transferase (GST) fusion
      proteins in insect cells using a Baculovirus expression system. The hybridomas
      were initially screened by ELISA against the GST-5-HT2AR recombinant proteins and
      subsequently against GST control proteins to eliminate clones with unwanted
      reactivity. They were further tested by Western blotting against recombinant GST
      5-HT2AR, rat and human brain lysate, and lysate from cell lines transfected with
      5-HT2AR cDNA. One of the MAbs G186-1117, which recognizes a portion of the 5
      HT2AR N-terminus, was selected for further characterization. G186-1117 reacted
      with a band of molecular size 55 kD corresponding to the predicted size of 5
      HT2AR in lysates from rat brain and a 5-HT2AR-transfected cell line. Its
      specificity was further confirmed by adsorption of immunoreactivity with
      recombinant 5-HT2AR but not with recombinant 5-HT2BR and 5-HT2CR. Rat brain
      sections and Schwann cell cultures were immunohistochemically labeled with this
      MAb. G186-1117 showed differential staining in various regions of the rat brain,
      varying from regions with no staining to regions of intense reactivity. In
      particular, staining of cell bodies and dendrites of the pyramidal neurons in the
      cortex was observed, which is in agreement with observations of
      electrophysiological studies.

PMID- 9632741
TI  - Localization of xenobiotic-responsive element binding protein in rat hepatocyte
      nuclei after methylcholanthrene administration as revealed by in situ
      Southwestern hybridization.
AB  - Xenobiotic-responsive element binding protein (XRE-BP), a heterodimer of aryl
      hydrocarbon receptor (AhR) and its nuclear translocator (Arnt), regulates the
      transcription of cytochrome P-450 1A1 gene (CYP1A1) through XRE in response to
      xenobiotic inducers. For a better understanding of the regulatory mechanism of
      CYP1A1 through XRE, localization of XRE-BP was examined in liver sections or
      isolated hepatocyte nuclei from control and 3-methylcholanthrene (MC)-treated
      rats by in situ Southwestern hybridization, using synthetic XRE as a probe, and
      was observed by confocal laser scanning microscopy and electron microscopy. Gel
      mobility shift assay and competitive binding assay showed specificity of the
      synthetic XRE probe. XRE-BP was exclusively localized in hepatocyte nuclei in
      liver sections from animals 3 hr after MC injection, whereas the protein was
      absent in hepatocyte cytoplasm in MC-treated animals and in hepatocyte nuclei and
      cytoplasm in control animals. In isolated hepatocyte nuclei, XRE-BP began to
      accumulate in the central region between 0.5 and 3 hr, showed a peak between 3
      and 6 hr, decreased gradually between 6 and 72 hr, and disappeared at 72 hr after
      MC injection. The protein was scarce in peripheral and nucleolar regions of the
      nucleus. Therefore, XRE-BP is formed in the nuclei of hepatocytes after MC
      stimulation. In addition, XRE-BP was found in isolated hepatocyte nuclei from
      control animals after preincubation with cytoplasmic lysate from MC-treated
      animals, although the protein was absent in the nuclei before the preincubation.
      These findings strongly suggest that AhR translocates from hepatocyte cytoplasm
      to the nucleus and forms XRE-BP in the nucleus after MC stimulation.

PMID- 9632742
TI  - Detection of deoxyribonuclease I along the secretory pathway in Paneth cells of
      human small intestine.
AB  - The expression and distribution of deoxyribonuclease I (DNase I) in human
      duodenum, jejunum and ileum were examined by DNase I activity assay and the
      reverse transcriptase-polymerase chain reaction (RT-PCR), immunofluorescence, in
      situ hybridization, and immunocytochemical ultrastructural analyses. High levels
      of DNase I were detected in the cytoplasm of Paneth cells in human small
      intestine. A tissue homogenate fraction rich in Paneth cells showed strong DNase
      I-specific enzymatic activity. Immunofluorescence analysis using several specific
      anti-human DNase I antibodies showed very strong immunoreactivity in the
      cytoplasm of every Paneth cell. In situ hybridization demonstrated high levels of
      DNase I mRNA in Paneth cells. Immunogold electron microscopy revealed gold
      particles localized along the secretory pathway, with the exocrine secretory
      granules mostly labeled. Our findings strongly suggest that Paneth cells
      synthesize and secrete DNase I into the intestinal lumen.

PMID- 9632743
TI  - Membrane dipeptidase in the pig exocrine pancreas. Ultrastructural localization
      and secretion.
AB  - The GPI-anchored membrane dipeptidase is the major peptidase activity of the
      secretory granule membrane in the exocrine pancreas. The enzyme is also found in
      the granule content and in pancreatic secretions. Immunocytochemical localization
      confirmed its location in the granule membrane and in the acinar cell apical
      plasma membrane. In the endoplasmic reticulum and Golgi, membrane dipeptidase was
      strictly membrane-bound. There was no membrane dipeptidase in duct cells. The
      release of membrane dipeptidase from the membrane starts in the immature granule.
      To identify the mechanism responsible for its release, secretions were collected
      from cannulated conscious pig under basal conditions and atropine perfusion. The
      latter treatment caused complete inhibition of protein secretion but had a
      negligible effect on membrane dipeptidase activity in the secretions. In
      secretions, membrane dipeptidase partitioned into the detergent-rich phase on
      phase separation in Triton X-114, whereas treatment with bacterial
      phosphatidylinositol-specific phospholipase C caused the peptidase to partition
      into the aqueous phase, indicating that the secreted enzyme could come from
      shedding of membrane fragments at the apical surface or via the action of a
      previously characterized phospholipase A activity.

PMID- 9632744
TI  - Immunoelectronmicroscopy of soluble and membrane proteins with a sensitive
      postembedding method.
AB  - The application of immunoelectronmicroscopy to soluble proteins is limited
      because soluble proteins can redistribute during fixation. Fixation may also
      adversely affect the recognition of proteins associated with membranes. We show
      here how displacements of soluble proteins can be prevented and antigen
      sensitivity improved by freeze-substitution immunocytochemistry. The usefulness
      of this method for soluble cytoplasmic proteins is demonstrated for the twitchin
      protein in Aplysia muscle and the kinesin motor proteins in squid giant axons, in
      which the sizes of various cytoplasmic pools of kinesins are estimated. The
      utility for membrane proteins present in small numbers of copies is demonstrated
      by labeling a glutamate receptor subunit in mouse cerebellar cortex and the ZO-1
      protein in tight junctions between MDCK cells. Thus, freeze-substitution
      immunocytochemistry can show the native distribution of both soluble and membrane
      proteins labeled with polyclonal antibodies and, at the same time, can reveal
      structural features comparable to those in chemically fixed or osmium freeze
      substituted samples.

PMID- 9632745
TI  - Localization of carbonic anhydrase IV in rat and human heart muscle.
AB  - We investigated carbonic anhydrase IV (CA IV) in rat and human heart with
      immunohistochemical methods by both light and electron microscopy. In
      cryosections that were incubated with anti-CA IV/FITC, the capillaries showed a
      strong reaction for CA IV. In paraffin and semithin sections treated with anti-CA
      IV/ABC (avidin-biotin-peroxidase complex) blood vessels, capillaries, and
      sarcolemma (SL) were positively stained. By staining ultrathin sections with anti
      CA IV/immunogold, CA IV could also be demonstrated at the latter two locations,
      including the specialized sarcolemmal structures intercalated discs, and T
      tubules. In addition, by this method CA IV was seen to be associated with the
      sarcoplasmic reticulum (SR). The absence of immunostaining in SR and/or SL with
      some techniques probably indicates a problem of accessibility of the antigenic
      sites. In line with the immunohistochemical results, CA IV mRNA expression was
      visualized in both endothelial and muscle cells by in situ hybridization
      histochemistry.

PMID- 9632746
TI  - Intranuclear distribution of HMGI/Y proteins. An immunocytochemical study.
AB  - The intranuclear distribution of HMGI/Y proteins was analyzed by
      immunofluorescent staining in several cell lines using a polyclonal antibody that
      stained a fibrogranular network. In actively growing 3T3 fibroblasts, HMGI/Y
      proteins were mainly localized to heterochromatin masses, whereas in quiescent
      cells they were more diffusely distributed. Double labeling experiments showed a
      co-localization of HMGI/Y with DNA topoisomerase IIalpha. These results are in
      agreement with previously published biochemical data and indicate a possible
      involvement of HMGI/Y proteins in several nuclear functions, including chromatin
      organization and gene expression.

PMID- 9632747
TI  - RB and c-Myc activate expression of the E-cadherin gene in epithelial cells
      through interaction with transcription factor AP-2.
AB  - E-cadherin plays a pivotal role in the biogenesis of the first epithelium during
      development, and its down-regulation is associated with metastasis of carcinomas.
      We recently reported that inactivation of RB family proteins by simian virus 40
      large T antigen (LT) in MDCK epithelial cells results in a mesenchymal conversion
      associated with invasiveness and a down-regulation of c-Myc. Reexpression of RB
      or c-Myc in such cells allows the reexpression of epithelial markers including E
      cadherin. Here we show that both RB and c-Myc specifically activate transcription
      of the E-cadherin promoter in epithelial cells but not in NIH 3T3 mesenchymal
      cells. This transcriptional activity is mediated in both cases by the
      transcription factor AP-2. In vitro AP-2 and RB interaction involves the N
      terminal domain of AP-2 and the oncoprotein binding domain and C-terminal domain
      of RB. In vivo physical interaction between RB and AP-2 was demonstrated in MDCK
      and HaCat cells. In LT-transformed MDCK cells, LT, RB, and AP-2 were all
      coimmunoprecipitated by each of the corresponding antibodies, and a mutation of
      the RB binding domain of the oncoprotein inhibited its binding to both RB and AP
      2. Taken together, our results suggest that there is a tripartite complex between
      LT, RB, and AP-2 and that the physical and functional interactions between LT and
      AP-2 are mediated by RB. Moreover, they define RB and c-Myc as coactivators of AP
      2 in epithelial cells and shed new light on the significance of the LT-RB
      complex, linking it to the dedifferentiation processes occurring during tumor
      progression. These data confirm the important role for RB and c-Myc in the
      maintenance of the epithelial phenotype and reveal a novel mechanism of gene
      activation by c-Myc.

PMID- 9632748
TI  - Cyclin-stimulated binding of Cks proteins to cyclin-dependent kinases.
AB  - Although Cks proteins were the first identified binding partners of cyclin
      dependent protein kinases (cdks), their cell cycle functions have remained
      unclear. To help elucidate the function of Cks proteins, we examined whether
      their binding to p34(cdc2) (the mitotic cdk) varies during the cell cycle in
      Xenopus egg extracts. We observed that binding of human CksHs2 to p34(cdc2) was
      stimulated by cyclin B. This stimulation was dependent on the activating
      phosphorylation of p34(cdc2) on Thr-161, which follows cyclin binding and is
      mediated by the cdk-activating kinase. Neither the inhibitory phosphorylations of
      p34(cdc2) nor the catalytic activity of p34(cdc2) was required for this
      stimulation. Stimulated binding of CksHs2 to another cdk, p33(cdk2), required
      both cyclin A and activating phosphorylation. Our findings support recent models
      that suggest that Cks proteins target active forms of p34(cdc2) to substrates.

PMID- 9632749
TI  - Role of histone H1 as an architectural determinant of chromatin structure and as
      a specific repressor of transcription on Xenopus oocyte 5S rRNA genes.
AB  - We explore the role of histone H1 as a DNA sequence-dependent architectural
      determinant of chromatin structure and of transcriptional activity in chromatin.
      The Xenopus laevis oocyte- and somatic-type 5S rRNA genes are differentially
      transcribed in embryonic chromosomes in vivo depending on the incorporation of
      somatic histone H1 into chromatin. We establish that this effect can be
      reconstructed at the level of a single nucleosome. H1 selectively represses
      oocyte-type 5S rRNA genes by directing the stable positioning of a nucleosome
      such that transcription factors cannot bind to the gene. This effect does not
      occur on the somatic-type genes. Histone H1 binds to the 5' end of the nucleosome
      core on the somatic 5S rRNA gene, leaving key regulatory elements in the promoter
      accessible, while histone H1 binds to the 3' end of the nucleosome core on the
      oocyte 5S rRNA genes, specifically blocking access to a key promoter element (the
      C box). TFIIIA can bind to the somatic 5S rRNA gene assembled into a nucleosome
      in the presence of H1. Because H1 binds with equivalent affinities to nucleosomes
      containing either gene, we establish that it is the sequence-selective assembly
      of a specific repressive chromatin structure on the oocyte 5S rRNA genes that
      accounts for differential transcriptional repression. Thus, general components of
      chromatin can determine the assembly of specific regulatory nucleoprotein
      complexes.

PMID- 9632751
TI  - Characterization of structural p53 mutants which show selective defects in
      apoptosis but not cell cycle arrest.
AB  - Suppression of tumor cell growth by p53 results from the activation of both
      apoptosis and cell cycle arrest, functions which have been shown to be separable
      activities of p53. We have characterized a series of p53 mutants with amino acid
      substitutions at residue 175 and show that these mutants fall into one of three
      classes: class I, which is essentially wild type for apoptotic and cell cycle
      arrest functions; class II, which retains cell cycle arrest activity but is
      impaired in the induction of apoptosis; and class III, which is defective in both
      activities. Several residue 175 mutants which retain cell cycle arrest function
      have been detected in cancers, and we show that these have lost apoptotic
      function. Furthermore, several class II mutants have been found to be temperature
      sensitive for apoptotic activity while showing constitutive cell cycle arrest
      function. Taken together, these mutants comprise an excellent system with which
      to investigate the biochemical nature of p53-mediated apoptosis, the function of
      principal importance in tumor suppression. All of the mutants that showed loss of
      apoptotic function also showed defects in the activation of promoters from the
      potential apoptotic targets Bax and the insulin-like growth factor-binding
      protein 3 gene (IGF-BP3), and a correlation between full apoptotic activity and
      activation of both of these promoters was also seen with the temperature
      sensitive mutants. However, a role for additional apoptotic activities of p53 was
      suggested by the observation that some mutants retained significant apoptotic
      function despite being impaired in the activation of Bax- and IGF-BP3-derived
      promoters. In contrast to the case of transcriptional activation, a perfect
      correlation between transcriptional repression of the c-fos promoter and the
      ability to induce apoptosis was seen, although the observation that Bax
      expression induced a similar repression of transcription from this promoter
      suggests that this may be a consequence, rather than a cause, of apoptotic death.

PMID- 9632750
TI  - Pheromone-dependent G1 cell cycle arrest requires Far1 phosphorylation, but may
      not involve inhibition of Cdc28-Cln2 kinase, in vivo.
AB  - In yeast, the pheromone alpha-factor acts as an antiproliferative factor that
      induces G1 arrest and cellular differentiation. Previous data have indicated that
      Far1, a factor dedicated to pheromone-induced cell cycle arrest, is under
      positive and negative posttranslational regulation. Phosphorylation by the
      pheromone-stimulated mitogen-activated protein (MAP) kinase Fus3 has been thought
      to enhance the binding of Far1 to G1-specific cyclin-dependent kinase (Cdk)
      complexes, thereby inhibiting their catalytic activity. Cdk-dependent
      phosphorylation events were invoked to account for the high instability of Far1
      outside early G1 phase. To confirm any functional role of Far1 phosphorylation,
      we undertook a systematic mutational analysis of potential MAP kinase and Cdk
      recognition motifs. Two putative phosphorylation sites that strongly affect Far1
      behavior were identified. A change of serine 87 to alanine prevents the cell
      cycle-dependent degradation of Far1, causing enhanced sensitivity to pheromone.
      In contrast, threonine 306 seems to be an important recipient of an activating
      modification, as substitutions at this position abolish the G1 arrest function of
      Far1. Only the phosphorylated wild-type Far1 protein, not the T306-to-A
      substitution product, can be found in stable association with the Cdc28-Cln2
      complex. Surprisingly, Far1-associated Cdc28-Cln2 complexes are at best
      moderately inhibited in immunoprecipitation kinase assays, suggesting
      unconventional inhibitory mechanisms of Far1.

PMID- 9632752
TI  - AP1 regulation of proliferation and initiation of apoptosis in erythropoietin
      dependent erythroid cells.
AB  - The transcription factor AP1 has been implicated in the induction of apoptosis in
      cells in response to stress factors and growth factor withdrawal. We report here
      that AP1 is necessary for the induction of apoptosis following hormone withdrawal
      in the erythropoietin (EPO)-dependent erythroid cell line HCD57. AP1 DNA binding
      activity increased upon withdrawal of HCD57 cells from EPO. A dominant negative
      AP1 mutant rendered these cells resistant to apoptosis induced by EPO withdrawal
      and blocked the downregulation of Bcl-XL. JunB is a major binding protein in the
      AP1 complex observed upon EPO withdrawal; JunB but not c-Jun was present in the
      AP1 complex 3 h after EPO withdrawal in HCD57 cells, with a concurrent increase
      in junB message and protein. Furthermore, analysis of AP1 DNA binding activity in
      an apoptosis-resistant subclone of HCD57 revealed a lack of induction in AP1 DNA
      binding activity and no change in junB mRNA levels upon EPO withdrawal. In
      addition, we determined that c-Jun and AP1 activities correlated with EPO-induced
      proliferation and/or protection from apoptosis. AP1 DNA binding activity
      increased over the first 3 h following EPO stimulation of HCD57 cells, and
      suppression of AP1 activity partially inhibited EPO-induced proliferation. c-Jun
      but not JunB was present in the AP1 complex 3 h after EPO addition. These results
      implicate AP1 in the regulation of proliferation and survival of erythroid cells
      and suggest that different AP1 factors may play distinct roles in both triggering
      apoptosis (JunB) and protecting erythroid cells from apoptosis (c-Jun).

PMID- 9632753
TI  - Requirement for activation of the serine-threonine kinase Akt (protein kinase B)
      in insulin stimulation of protein synthesis but not of glucose transport.
AB  - A wide variety of biological activities including the major metabolic actions of
      insulin is regulated by phosphatidylinositol (PI) 3-kinase. However, the
      downstream effectors of the various signaling pathways that emanate from PI 3
      kinase remain unclear. Akt (protein kinase B), a serine-threonine kinase with a
      pleckstrin homology domain, is thought to be one such downstream effector. A
      mutant Akt (Akt-AA) in which the phosphorylation sites (Thr308 and Ser473)
      targeted by growth factors are replaced by alanine has now been shown to lack
      protein kinase activity and, when overexpressed in CHO cells or 3T3-L1 adipocytes
      with the use of an adenovirus vector, to inhibit insulin-induced activation of
      endogenous Akt. Akt-AA thus acts in a dominant negative manner in intact cells.
      Insulin-stimulated protein synthesis, which is sensitive to wortmannin, a
      pharmacological inhibitor of PI 3-kinase, was abolished by overexpression of Akt
      AA without an effect on amino acid transport into the cells, suggesting that Akt
      is required for insulin-stimulated protein synthesis. Insulin activation of p70
      S6 kinase was inhibited by approximately 75% in CHO cells and approximately 30%
      in 3T3-L1 adipocytes, whereas insulin-induced activation of endogenous Akt was
      inhibited by 80 to 95%, by expression of Akt-AA. Thus, Akt activity appears to be
      required, at least in part, for insulin stimulation of p70 S6 kinase. However,
      insulin-stimulated glucose uptake in both CHO cells and 3T3-L1 adipocytes was not
      affected by overexpression of Akt-AA, suggesting that Akt is not required for
      this effect of insulin. These data indicate that Akt acts as a downstream
      effector in some, but not all, of the signaling pathways downstream of PI 3
      kinase.

PMID- 9632754
TI  - Differential effects of protein kinase A on Ras effector pathways.
AB  - Ras mutants with the ability to interact with different effectors have played a
      critical role in the identification of Ras-dependent signaling pathways. We used
      two mutants, RasS35 and RasG37, which differ in their ability to bind Raf-1, to
      examine Ras-dependent signaling in thyroid epithelial cells. Wistar rat thyroid
      cells are dependent upon thyrotropin (TSH) for growth. Although TSH-stimulated
      mitogenesis requires Ras, TSH activates protein kinase A (PKA) and downregulates
      signaling through Raf and the mitogen-activated protein kinase (MAPK) cascade.
      Cells expressing RasS35, a mutant which binds Raf, or RasG37, a mutant which
      binds RalGDS, exhibited TSH-independent proliferation. RasS35 stimulated
      morphological transformation and anchorage-independent growth. RasG37 stimulated
      proliferation but not transformation as measured by these indices. TSH exerted
      markedly different effects on the Ras mutants and transiently repressed MAPK
      phosphorylation in RasS35-expressing cells. In contrast, TSH stimulated MAPK
      phosphorylation and growth in cells expressing RasG37. The Ras mutants, in turn,
      exerted differential effects on TSH signaling. RasS35 abolished TSH-stimulated
      changes in cell morphology and thyroglobulin expression, while RasG37 had no
      effect on these activities. Together, the data indicate that cross talk between
      Ras and PKA discriminates between distinct Ras effector pathways.

PMID- 9632755
TI  - SBA1 encodes a yeast hsp90 cochaperone that is homologous to vertebrate p23
      proteins.
AB  - The Saccharomyces cerevisiae SBA1 gene was cloned by PCR amplification from yeast
      genomic DNA following its identification as encoding an ortholog of human p23, an
      Hsp90 cochaperone. The SBA1 gene product is constitutively expressed and
      nonessential, although a disruption mutant grew more slowly than the wild type at
      both 18 and 37 degreesC. A double deletion of SBA1 and STI1, encoding an Hsp90
      cochaperone, displayed synthetic growth defects. Affinity isolation of histidine
      tagged Sba1p (Sba1(His6)) after expression in yeast led to coisolation of Hsp90
      and the cyclophilin homolog Cpr6. Using an in vitro assembly assay, purified
      Sba1(His6) bound to Hsp90 only in the presence of adenosine 5'-O-(3
      thiotriphosphate) or adenyl-imidodiphosphate. Furthermore, interaction between
      purified Sba1(His6) and Hsp90 in yeast extracts was inhibited by the benzoquinoid
      ansamycins geldanamycin and macbecin. The in vitro assay was also used to
      identify residues in Hsp90 that are important for complex formation with
      Sba1(His6), and residues in both the N-terminal nucleotide binding domain and C
      terminal half were characterized. In vivo analysis of known Hsp90 substrate
      proteins revealed that Sba1 loss of function had only a mild effect on the
      activity of the tyrosine kinase v-Src and steroid hormone receptors.

PMID- 9632756
TI  - Activation of c-myc gene expression by tumor-derived p53 mutants requires a
      discrete C-terminal domain.
AB  - Mutation of the p53 tumor suppressor gene is the most common genetic alteration
      in human cancer, and tumors that express mutant p53 may be more aggressive and
      have a worse prognosis than p53-null cancers. Mutant p53 enhances tumorigenicity
      in the absence of a transdominant negative mechanism, and this tumor-promoting
      activity correlates with its ability to transactivate reporter genes in transient
      transfection assays. However, the mechanism by which mutant p53 functions in
      transactivation and its endogenous cellular targets that promote tumorigenicity
      are unknown. Here we report that (i) mutant p53 can regulate the expression of
      the endogenous c-myc gene and is a potent activator of the c-myc promoter; (ii)
      the region of mutant p53 responsiveness in the c-myc gene has been mapped to the
      3' end of exon 1; (iii) the mutant p53 response region is position and
      orientation dependent and therefore does not function as an enhancer; and (iv)
      transactivation by mutant p53 requires the C terminus, which is not essential for
      wild-type p53 transactivation. These data suggest that it may be possible to
      selectively inhibit mutant p53 gain of function and consequently reduce the
      tumorigenic potential of cancer cells. A possible mechanism for transactivation
      of the c-myc gene by mutant p53 is proposed.

PMID- 9632758
TI  - Interaction of TATA-binding protein with upstream activation factor is required
      for activated transcription of ribosomal DNA by RNA polymerase I in Saccharomyces
      cerevisiae in vivo.
AB  - Previous in vitro studies have shown that initiation of transcription of
      ribosomal DNA (rDNA) in the yeast Saccharomyces cerevisiae involves an
      interaction of upstream activation factor (UAF) with the upstream element of the
      promoter, forming a stable UAF-template complex; together with TATA-binding
      protein (TBP), UAF then recruits an essential factor, core factor (CF), to the
      promoter, forming a stable preinitiation complex. TBP interacts with both UAF and
      CF in vitro. In addition, a subunit of UAF, Rrn9p, interacts with TBP in vitro
      and in the two-hybrid system, suggesting the possible importance of this
      interaction for UAF function. Using the yeast two-hybrid system, we have
      identified three mutations in RRN9 that abolish the interaction of Rrn9p with TBP
      without affecting its interaction with Rrn10p, another subunit of UAF. Yeast
      cells containing any one of these individual mutations, L110S, L269P, or L274Q,
      did not show any growth defects. However, cells containing a combination of L110S
      with one of the other two mutations showed a temperature-sensitive phenotype, and
      this phenotype was suppressed by fusing the mutant genes to SPT15, which encodes
      TBP. In addition, another mutation (F186S), which disrupts both Rrn9p-TBP and
      Rrn9p-Rrn10p interactions in the two-hybrid system, abolished UAF function in
      vivo, and this mutational defect was suppressed by fusion of the mutant gene to
      SPT15 combined with overexpression of Rrn10p. These experiments demonstrate that
      the interaction of UAF with TBP, which is presumably achieved by the interaction
      of Rrn9p with TBP, is indeed important for high-level transcription of rDNA by
      RNA polymerase I in vivo.

PMID- 9632757
TI  - Cyclosporin A-sensitive transcription factor Egr-3 regulates Fas ligand
      expression.
AB  - Activation-induced transcriptional upregulation of the ligand for Fas (FasL) and
      the resulting apoptosis of Fas-bearing cells constitute essential steps in a host
      of normal and pathological processes. Here we describe an activation-inducible
      cis-acting regulatory element in the fasL promoter that is required for gene
      expression. Oligonucleotide competition and antibody supershift analyses
      identified two activation-induced DNA-binding species: Egr-1 (NGFI-A, krox-24,
      zif268, TIS-8), a transcription factor that has been implicated in growth,
      differentiation, and apoptosis; and Egr-3 (PILOT), a transcription factor of no
      previously known function. Activation-induced expression of Egr-3, like that of
      FasL, was inhibited by cyclosporin A, whereas expression of Egr-1 was unaffected.
      Transient expression of Egr-3 alone increased fasL promoter activity in a
      cyclosporin A-insensitive manner, whereas expression of Egr-1 had little effect.
      Moreover, endogenous fasL mRNA was induced in nonlymphoid cells by forced
      expression of Egr-3 in the absence of any other stimulus. These studies identify
      a critical Egr family-binding site in the fasL promoter and demonstrate that
      activation-induced Egr-3, but not Egr-1, directly upregulates fasL transcription
      in response to activating stimuli.

PMID- 9632759
TI  - Identification of the cytoplasmic regions of fibroblast growth factor (FGF)
      receptor 1 which play important roles in induction of neurite outgrowth in PC12
      cells by FGF-1.
AB  - Fibroblast growth factor 1 (FGF-1) induces neurite outgrowth in PC12 cells.
      Recently, we have shown that the FGF receptor 1 (FGFR-1) is much more potent than
      FGFR-3 in induction of neurite outgrowth. To identify the cytoplasmic regions of
      FGFR-1 that are responsible for the induction of neurite outgrowth in PC12 cells,
      we took advantage of this difference and prepared receptor chimeras containing
      different regions of the FGFR-1 introduced into the FGFR-3 protein. The chimeric
      receptors were introduced into FGF-nonresponsive variant PC12 cells (fnr-PC12
      cells), and their ability to mediate FGF-stimulated neurite outgrowth of the
      cells was assessed. The juxtamembrane (JM) and carboxy-terminal (COOH) regions of
      FGFR-1 were identified as conferring robust and moderate abilities, respectively,
      for induction of neurite outgrowth to FGFR-3. Analysis of FGF-stimulated
      activation of signal transduction revealed that the JM region of FGFR-1 conferred
      strong and sustained tyrosine phosphorylation of several cellular proteins and
      activation of MAP kinase. The SNT/FRS2 protein was demonstrated to be one of the
      cellular substrates preferentially phosphorylated by chimeras containing the JM
      domain of FGFR-1. SNT/FRS2 links FGF signaling to the MAP kinase pathway. Thus,
      the ability of FGFR-1 JM domain chimeras to induce strong sustained
      phosphorylation of this protein would explain the ability of these chimeras to
      activate MAP kinase and hence neurite outgrowth. The role of the COOH region of
      FGFR-1 in induction of neurite outgrowth involved the tyrosine residue at amino
      acid position 764, a site required for phospholipase C gamma binding and
      activation, whereas the JM region functioned primarily through a non
      phosphotyrosine-dependent mechanism. In contrast, assessment of the chimeras in
      the pre-B lymphoid cell line BaF3 for FGF-1-induced mitogenesis revealed that the
      JM region did not play a role in this cell type. These data indicate that FGFR
      signaling can be regulated at the level of intracellular interactions and that
      signaling pathways for neurite outgrowth and mitogenesis use different regions of
      the FGFR.

PMID- 9632761
TI  - Tyrosine phosphorylation of cdc2 is required for the replication checkpoint in
      Schizosaccharomyces pombe.
AB  - The DNA replication checkpoint inhibits mitosis in cells that are unable to
      replicate their DNA, as when nucleotide biosynthesis is inhibited by hydroxyurea.
      In the fission yeast Schizosaccharomyces pombe, genetic evidence suggests that
      this checkpoint involves the inhibition of Cdc2 activity through the
      phosphorylation of tyrosine-15. On the contrary, a recent biochemical study
      indicated that Cdc2 is in an activated state during a replication checkpoint,
      suggesting that phosphorylation of Cdc2 on tyrosine-15 is not part of the
      replication checkpoint mechanism. We have undertaken biochemical and genetic
      studies to resolve this controversy. We report that the DNA replication
      checkpoint in S. pombe is abrogated in cells that carry the allele cdc2-Y15F,
      expressing an unphosphorylatable form of Cdc2. Furthermore, Cdc2 isolated from
      replication checkpoint-arrested cells can be activated in vitro by Cdc25, the
      tyrosine phosphatase responsible for dephosphorylating Cdc2 in vivo, to the same
      extent as Cdc2 isolated from cdc25ts-blocked cells, indicating that hydroxyurea
      treatment causes Cdc2 activity to be maintained at a low level that is
      insufficient to induce mitosis. These studies show that inhibitory tyrosine-15
      phosphorylation of Cdc2 is essential for the DNA replication checkpoint and
      suggests that Cdc25, and/or one or both of Wee1 and Mik1, the tyrosine kinases
      that phosphorylate Cdc2, are regulated by the replication checkpoint.

PMID- 9632760
TI  - Even-skipped represses transcription by binding TATA binding protein and blocking
      the TFIID-TATA box interaction.
AB  - The Drosophila homeodomain protein Even-skipped (Eve) is a transcriptional
      repressor, and previous studies have suggested that it functions by interfering
      with the basal transcription machinery. Here we describe experiments indicating
      that the mechanism of Eve repression involves a direct interaction with the TATA
      binding protein (TBP) that blocks binding of TBP-TFIID to the promoter. We first
      compared Eve activities in in vitro transcription systems reconstituted with
      either all the general transcription factors or only TBP, TFIIB, TFIIF30, and RNA
      polymerase II. In each case, equivalent and very efficient levels of repression
      were observed, indicating that no factors other than those in the minimal system
      are required for repression. We then show that Eve can function efficiently when
      its recognition sites are far from the promoter and that the same regions of Eve
      required for repression in vivo are necessary and sufficient for in vitro
      repression. This includes, in addition to an Ala-Pro-rich region, residues within
      the homeodomain. Using GAL4-Eve fusion proteins, we demonstrate that the
      homeodomain plays a role in repression in addition to DNA binding, which is to
      facilitate interaction with TBP. Single-round transcription experiments indicate
      that Eve must function prior to TBP binding to the promoter, suggesting a
      mechanism whereby Eve represses by competing with the TATA box for TBP binding.
      Consistent with this, excess TATA box-containing oligonucleotide is shown to
      specifically and efficiently disrupt the TBP-Eve interaction. Importantly, we
      show that Eve binds directly to TFIID and that this interaction can also be
      disrupted by the TATA oligonucleotide. We conclude that Eve represses
      transcription via a direct interaction with TBP that blocks TFIID binding to the
      promoter.

PMID- 9632762
TI  - Mutational analysis of an RNA recognition element that mediates localization of
      bicoid mRNA.
AB  - Localization signals are RNA regulatory elements that direct the localization of
      mRNAs to subcellular sites. Localization signals presumably function by mediating
      RNA recognition events through which the mRNA becomes associated with the
      localization machinery. At present little is known about individual RNA
      recognition events, which in turn has limited progress in identifying the trans
      acting binding factors involved in these events. Here we describe a detailed
      characterization of the RNA elements required for the RNA recognition event,
      event A, that initiates localization of bicoid mRNA in the Drosophila ovary. One
      element is a helix in which nucleotide identities are not important, suggesting
      that it plays a primarily structural role. Immediately adjacent to the helix is a
      recognition domain in which the identities of some, but not all, nucleotides are
      important for function. Comparison of two related but different RNAs that both
      support recognition event A further defines the important features of the
      recognition domain.

PMID- 9632763
TI  - Cytomegalovirus activates interferon immediate-early response gene expression and
      an interferon regulatory factor 3-containing interferon-stimulated response
      element-binding complex.
AB  - Interferon establishes an antiviral state in numerous cell types through the
      induction of a set of immediate-early response genes. Activation of these genes
      is mediated by phosphorylation of latent transcription factors of the STAT
      family. We found that infection of primary foreskin fibroblasts with human
      cytomegalovirus (HCMV) causes selective transcriptional activation of the
      alpha/beta-interferon-responsive ISG54 gene. However, no activation or nuclear
      translocation of STAT proteins was detected. Activation of ISG54 occurs
      independent of protein synthesis but is prevented by protein tyrosine kinase
      inhibitors. Further analysis revealed that HCMV infection induced the DNA binding
      of a novel complex, tentatively called cytomegalovirus-induced interferon
      stimulated response element binding factor (CIF). CIF is composed, at least in
      part, of the recently identified interferon regulatory factor 3 (IRF3), but it
      does not contain the STAT1 and STAT2 proteins that participate in the formation
      of interferon-stimulated gene factor 3. IRF3, which has previously been shown to
      possess no intrinsic transcriptional activation potential, interacts with the
      transcriptional coactivator CREB binding protein, but not with p300, to form CIF.
      Activating interferon-stimulated genes without the need for prior synthesis of
      interferons might provide the host cell with a potential shortcut in the
      activation of its antiviral defense.

PMID- 9632765
TI  - Xenopus TFIIIA gene transcription is dependent on cis-element positioning and
      chromatin structure.
AB  - The Xenopus TFIIIA gene is transcribed very efficiently in oocytes. In addition
      to a TATA element at -30, we show that from -425 to +7 the TFIIIA gene contains
      only two positive cis elements centered at -267 (element 1) and -230 (element 2).
      This arrangement of the cis elements in the TFIIIA gene is striking because these
      two elements are positioned very close to each other yet separated from the TATA
      element by approximately 190 nucleotides. We show that the 190-nucleotide spacing
      between the TATA element and the upstream cis elements (elements 1 and 2) is
      critical for efficient transcription of the gene in oocytes and that a nucleosome
      is positioned in this intervening region. This nucleosome may act positively on
      TFIIIA transcription in oocytes by placing transcription factors bound at
      elements 1 and 2 in a favorable position relative to the transcription complex at
      the TATA element.

PMID- 9632764
TI  - Coactivation by OCA-B: definition of critical regions and synergism with general
      cofactors.
AB  - Molecular dissection of the B-cell-specific transcription coactivator OCA-B has
      revealed distinct regions important, respectively, for recruitment to
      immunoglobulin promoters through interaction with octamer-bound Oct-1 and for
      subsequent coactivator function. Further analysis of general coactivator
      requirements showed that selective removal of PC4 from the essential USA fraction
      severely impairs Oct-1 and OCA-B function in a cell-free system reconstituted
      with partially purified factors. Full activity can be restored by the combined
      action of recombinant PC4 and the PC4-depleted USA fraction, thus suggesting a
      joint requirement for PC4 and another, USA-derived component(s) for optimal
      function of Oct-1/OCA-B in the reconstituted system. Indeed, USA-derived PC2 was
      found to act synergistically with PC4 in reproducing the function of intact USA
      in the assay system. Consistent with the requirement for PC4 in the reconstituted
      system, OCA-B was found to interact directly with PC4. Surprisingly, however,
      removal of PC4 from the unfractionated nuclear extract has no detrimental effect
      on OCA-B/Oct-1-dependent transcription. These results lead to a general model for
      the synergistic function of activation domains in Oct-1 and OCA-B (mediated by
      the combined action of the multiple USA components) and, further, suggest a
      functional redundancy in general coactivators.

PMID- 9632766
TI  - Molecular mechanism governing heme signaling in yeast: a higher-order complex
      mediates heme regulation of the transcriptional activator HAP1.
AB  - Apart from serving as a prosthetic group in globins and enzymes, heme is a key
      regulator controlling a wide range of molecular and cellular processes involved
      in oxygen sensing and utilization. To gain insights into molecular mechanisms of
      heme signaling and oxygen sensing in eukaryotes, we investigated the yeast heme
      responsive transcriptional activator HAP1. HAP1 activity is regulated precisely
      and tightly by heme. Here we show that in the absence of heme, HAP1 forms a
      biochemically distinctive higher-order complex. Our data suggest that this
      complex contains HAP1 and four other cellular proteins including Hsp82 and Ydj1.
      The formation of this complex is directly correlated with HAP1 repression in the
      absence of heme, and mutational or heme disruption of the complex correlates with
      HAP1 activation, suggesting that this complex is responsible for heme regulation
      of HAP1 activity. Further, we determined HAP1 domains required for heme
      regulation: three domains-the dimerization domain, the heme domain, and the HRM7
      (heme-responsive motif 7) domain-cooperate to form the higher-order complex and
      mediate heme regulation. Strikingly, we uncovered a novel function for the HAP1
      dimerization domain: it not only allows dimerization but also provides critical
      functions in heme regulation and transcriptional activation. Our studies provide
      significant insights into the molecular events leading to heme activation of HAP1
      and may shed light on molecular mechanisms of various heme-controlled biological
      processes in diverse organisms.

PMID- 9632767
TI  - Role of phosphatidylinositol 4,5-bisphosphate in Ras/Rac-induced disruption of
      the cortactin-actomyosin II complex and malignant transformation.
AB  - Oncogenic Ras mutants such as v-Ha-Ras cause a rapid rearrangement of actin
      cytoskeleton during malignant transformation of fibroblasts or epithelial cells.
      Both PI-3 kinase and Rac are required for Ras-induced malignant transformation
      and membrane ruffling. However, the signal transduction pathway(s) downstream of
      Rac that leads to membrane ruffling and other cytoskeletal change(s) as well as
      the exact biochemical nature of the cytoskeletal change remain unknown.
      Cortactin/EMS1 is the first identified molecule that is dissociated in a Rac
      phosphatidylinositol 4,5-biphosphate (PIP2)-dependent manner from the actin
      myosin II complex during Ras-induced malignant transformation; either the PIP2
      binder HS1 or the Rac blocker SCH51344 restores the ability of EMS1 to bind the
      complex and suppresses the oncogenicity of Ras. Furthermore, while PIP2 inhibits
      the actin-EMS1 interaction, HS1 reverses the PIP2 effect. Thus, we propose that
      PIP2, an end-product of the oncogenic Ras/PI-3 kinase/Rac pathway, serves as a
      second messenger in the Ras/Rac-induced disruption of the actin cytoskeleton and
      discuss the anticancer drug potential of PIP2-binding molecules.

PMID- 9632768
TI  - Identification of major binding proteins and substrates for the SH2-containing
      protein tyrosine phosphatase SHP-1 in macrophages.
AB  - The protein tyrosine phosphatase SHP-1 is a critical regulator of macrophage
      biology, but its detailed mechanism of action remains largely undefined. SHP-1
      associates with a 130-kDa tyrosyl-phosphorylated species (P130) in macrophages,
      suggesting that P130 might be an SHP-1 regulator and/or substrate. Here we show
      that P130 consists of two transmembrane glycoproteins, which we identify as PIR
      B/p91A and the signal-regulatory protein (SIRP) family member BIT. These proteins
      also form separate complexes with SHP-2. BIT, but not PIR-B, is in a complex with
      the colony-stimulating factor 1 receptor (CSF-1R), suggesting that BIT may direct
      SHP-1 to the CSF-1R. BIT and PIR-B bind preferentially to substrate-trapping
      mutants of SHP-1 and are hyperphosphorylated in macrophages from motheaten viable
      mice, which express catalytically impaired forms of SHP-1, indicating that these
      proteins are SHP-1 substrates. However, BIT and PIR-B are hypophosphorylated in
      motheaten macrophages, which completely lack SHP-1 expression. These data suggest
      a model in which SHP-1 dephosphorylates specific sites on BIT and PIR-B while
      protecting other sites from dephosphorylation via its SH2 domains. Finally, BIT
      and PIR-B associate with two tyrosyl phosphoproteins and a tyrosine kinase
      activity. Tyrosyl phosphorylation of these proteins and the level of the
      associated kinase activity are increased in the absence of SHP-1. Our data
      suggest that BIT and PIR-B recruit multiple signaling molecules to receptor
      complexes, where they are regulated by SHP-1 and/or SHP-2.

PMID- 9632769
TI  - Differential utilization of Ras signaling pathways by macrophage colony
      stimulating factor (CSF) and granulocyte-macrophage CSF receptors during
      macrophage differentiation.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony
      stimulating factor (M-CSF) independently stimulate the proliferation and
      differentiation of macrophages from bone marrow progenitor cells. Although the GM
      CSF and M-CSF receptors are unrelated, both couple to Ras-dependent signal
      transduction pathways, suggesting that these pathways might account for common
      actions of GM-CSF and M-CSF on the expression of macrophage-specific genes. To
      test this hypothesis, we have investigated the mechanisms by which GM-CSF and M
      CSF regulate the expression of the macrophage scavenger receptor A (SR-A) gene.
      We demonstrate that induction of the SR-A gene by M-CSF is dependent on AP-1 and
      cooperating Ets domain transcription factors that bind to sites in an M-CSF
      dependent enhancer located 4.1 to 4.5 kb upstream of the transcriptional start
      site. In contrast, regulation by GM-CSF requires a separate enhancer located 4.5
      to 4.8 kb upstream of the transcriptional start site that confers both immediate
      early and sustained transcriptional responses. Results of a combination of DNA
      binding experiments and functional assays suggest that immediate transcriptional
      responses are mediated by DNA binding proteins that are constitutively bound to
      the GM-CSF enhancer and are activated by Ras. At 12 to 24 h after GM-CSF
      treatment, the GM-CSF enhancer becomes further occupied by additional DNA binding
      proteins that may contribute to sustained transcriptional responses. In concert,
      these studies indicate that GM-CSF and M-CSF differentially utilize Ras-dependent
      signal transduction pathways to regulate scavenger receptor gene expression,
      consistent with the distinct functional properties of M-CSF- and GM-CSF-derived
      macrophages.

PMID- 9632770
TI  - Inhibition of clathrin-mediated endocytosis selectively attenuates specific
      insulin receptor signal transduction pathways.
AB  - To examine the role of clathrin-dependent insulin receptor internalization in
      insulin-stimulated signal transduction events, we expressed a dominant
      interfering mutant of dynamin (K44A/dynamin) by using a recombinant adenovirus in
      the H4IIE hepatoma and 3T3L1 adipocyte cell lines. Expression of K44A/dynamin
      inhibited endocytosis of the insulin receptor as determined by both cell surface
      radioligand binding and trypsin protection analysis. The inhibition of the
      insulin receptor endocytosis had no effect on either the extent of insulin
      receptor autophosphorylation or insulin receptor substrate 1 (IRS1) tyrosine
      phosphorylation. In contrast, expression of K44A/dynamin partially inhibited
      insulin-stimulated Shc tyrosine phosphorylation and activation of the mitogen
      activated protein kinases ERK1 and -2. Although there was an approximately 50%
      decrease in the insulin-stimulated activation of the phosphatidylinositol 3
      kinase associated with IRS1, insulin-stimulated Akt kinase phosphorylation and
      activation were unaffected. The expression of K44A/dynamin increased the basal
      rate of amino acid transport, which was additive with the effect of insulin but
      had no effect on the basal or insulin-stimulated DNA synthesis. In 3T3L1
      adipocytes, expression of K44A/dynamin increased the basal rate of glucose
      uptake, glycogen synthesis, and lipogenesis without any significant effect on
      insulin stimulation. Together, these data demonstrate that the acute actions of
      insulin are largely independent of insulin receptor endocytosis and are initiated
      by activation of the plasma membrane-localized insulin receptor.

PMID- 9632771
TI  - Identification and characterization of a constitutively active STAT5 mutant that
      promotes cell proliferation.
AB  - STAT (signal transducers and activators of transcription) proteins are
      transcription factors which are activated by phosphorylation on tyrosine residues
      upon stimulation by cytokines. Seven members of the STAT family are known,
      including the closely related STAT5A and STAT5B, which are activated by various
      cytokines. Except for prolactin-dependent beta-casein production in mammary gland
      cells, the biological consequences of STAT5 activation in various systems are not
      clear. We applied PCR-driven random mutagenesis and a retrovirus-mediated
      expression screening system to identify constitutively active forms of STAT5. By
      this strategy, we have identified a constitutively active STAT5 mutant which has
      two amino acid substitutions; one is located upstream of the putative DNA binding
      domain (H299R), and the other is located in the transactivation domain (S711F).
      The mutant STAT5 was constitutively phosphorylated on tyrosine residues,
      localized in the nucleus, and was transcriptionally active. Expression of the
      mutant STAT5 partially dispenses with interleukin 3 (IL-3) as a growth stimulant
      of IL-3-dependent cell lines. Further analyses of the mutant STAT5 have
      demonstrated that both of the mutations are required for nuclear localization,
      efficient transcriptional activation, and induction of IL-3-independent growth of
      an IL-3-dependent cell line, Ba/F3, and have indicated that a molecular basis for
      the constitutive activation is the stability of the phosphorylated form of the
      mutant STAT5.

PMID- 9632772
TI  - Schistosome satellite DNA encodes active hammerhead ribozymes.
AB  - Using a computer program designed to search for RNA structural motifs in sequence
      databases, we have found a hammerhead ribozyme domain encoded in the Smalpha
      repetitive DNA of Schistosoma mansoni. Transcripts of these repeats are expressed
      as long multimeric precursor RNAs that cleave in vitro and in vivo into unit
      length fragments. This RNA domain is able to engage in both cis and trans
      cleavage typical of the hammerhead ribozyme. Further computer analysis of S.
      mansoni DNA identified a potential trans cleavage site in the gene coding for a
      synaptobrevin-like protein, and RNA transcribed from this gene was efficiently
      cleaved by the Smalpha ribozyme in vitro. Similar families of repeats containing
      the hammerhead domain were found in the closely related Schistosoma haematobium
      and Schistosomatium douthitti species but were not present in Schistosoma
      japonicum or Heterobilharzia americana, suggesting that the hammerhead domain was
      not acquired from a common schistosome ancestor.

PMID- 9632774
TI  - Alternative splicing of the fibronectin EIIIB exon depends on specific TGCATG
      repeats.
AB  - The fibronectin EIIIB exon is alternatively spliced in a cell-type-specific
      manner, and TGCATG repeats in the intron downstream of EIIIB have been implicated
      in this regulation. Analysis of the intron sequence from several vertebrates
      shows that the pattern of repeats in the 3' half of the intron is evolutionarily
      conserved. Point mutations in certain highly conserved repeats greatly reduce
      EIIIB inclusion, suggesting that a multicomponent complex may recognize the
      repeats. Expression of the SR protein SRp40, SRp20, or ASF/SF2 stimulates EIIIB
      inclusion. Studies of the interplay between mutations in the repeats and SRp40
      stimulated inclusion suggest that the repeats are recognized in many, if not all,
      cell types, and that EIIIB inclusion may be regulated by quantitative changes in
      multiple factors.

PMID- 9632773
TI  - Differential requirements for alternative splicing and nuclear export functions
      of equine infectious anemia virus Rev protein.
AB  - The Rev protein of equine infectious anemia virus (ERev) exports unspliced and
      partially spliced viral RNAs from the nucleus. Like several cellular proteins,
      ERev regulates its own mRNA by mediating an alternative splicing event. To
      determine the requirements for these functions, we have identified ERev mutants
      that affect RNA export or both export and alternative splicing. Mutants were
      further characterized for subcellular localization, nuclear-cytoplasmic
      shuttling, and multimerization. None of the nuclear export signal (NES) mutants
      are defective for alternative splicing. Furthermore, the NES of ERev is similar
      in composition but distinct in spacing from other leucine-rich NESs. Basic
      residues at the C terminus of ERev are involved in nuclear localization, and
      disruption of the C-terminal residues affects both functions of ERev. ERev forms
      multimers, and no mutation disrupts this activity. In two mutants with
      substitutions of charged residues in the middle of ERev, RNA export is affected.
      One of these mutants is also defective for ERev-mediated alternative splicing but
      is identical to wild-type ERev in its localization, shuttling, and
      multimerization. Together, these results demonstrate that the two functions of
      ERev both require nuclear import and at least one other common activity, but RNA
      export can be separated from alternative splicing based on its requirement for a
      functional NES.

PMID- 9632775
TI  - TATA binding protein discriminates between different lesions on DNA, resulting in
      a transcription decrease.
AB  - DNA damage recognition by basal transcription factors follows different
      mechanisms. Using transcription-competition, nitrocellulose filter binding, and
      DNase I footprinting assays, we show that, although the general transcription
      factor TFIIH is able to target any kind of lesion which can be repaired by the
      nucleotide excision repair pathway, TATA binding protein (TBP)-TFIID is more
      selective in damage recognition. Only genotoxic agents which are able to induce
      kinked DNA structures similar to the one for the TATA box in its TBP complex are
      recognized. Indeed, DNase I footprinting patterns reveal that TBP protects
      equally 4 nucleotides upstream and 6 nucleotides downstream from the A-T (at
      position -29 of the noncoding strand) of the adenovirus major late promoter and
      from the G-G of a cisplatin-induced 1,2-d(GpG) cross-link. Together, our results
      may partially explain differences in transcription inhibition rates following DNA
      damage.

PMID- 9632776
TI  - Multiple functional domains of AML1: PU.1 and C/EBPalpha synergize with different
      regions of AML1.
AB  - Control elements of many genes are regulated by multiple activators working in
      concert to confer the maximal level of expression, but the mechanism of such
      synergy is not completely understood. The promoter of the human macrophage colony
      stimulating factor (M-CSF) receptor presents an excellent model with which we can
      study synergistic, tissue-specific activation for two reasons. First, myeloid
      specific expression of the M-CSF receptor is regulated transcriptionally by three
      factors which are crucial for normal hematopoiesis: PU.1, AML1, and C/EBPalpha.
      Second, these proteins interact in such a way as to demonstrate at least two
      examples of synergistic activation. We have shown that AML1 and C/EBPalpha
      activate the M-CSF receptor promoter in a synergistic manner. As we report here,
      AML1 also synergizes, and interacts physically, with PU. 1. Detailed analysis of
      the physical and functional interaction of AML1 with PU.1 and C/EBPalpha has
      revealed that the proteins contact one another through their DNA-binding domains
      and that AML1 exhibits cooperative DNA binding with C/EBPalpha but not with PU.1.
      This difference in DNA-binding abilities may explain, in part, the differences
      observed in synergistic activation. Furthermore, the activation domains of all
      three factors are required for synergistic activation, and the region of AML1
      required for synergy with PU.1 is distinct from that required for synergy with
      C/EBPalpha. These observations present the possibility that synergistic
      activation is mediated by secondary proteins contacted through the activation
      domains of AML1, C/EBPalpha, and PU.1.

PMID- 9632777
TI  - Simian virus 40 large T antigen stabilizes the TATA-binding protein-TFIIA complex
      on the TATA element.
AB  - Large T antigen (T antigen), the early gene product of simian virus 40 (SV40), is
      a potent transcriptional activator of both cellular and viral genes. Recently we
      have shown that T antigen is tightly associated with TFIID and, in this position,
      performs a TATA-binding protein (TBP)-associated factor (TAF)-like function.
      Based on this observation, we asked whether T antigen affected steps in
      preinitiation complex assembly. Using purified components in in vitro complex
      assembly assays, we found that T antigen specifically enhances the formation of
      the TBP-TFIIA complex on the TATA element. T antigen accomplishes this by
      increasing the rate of formation of the TBP-TFIIA complex on the TATA element and
      by stabilizing the complexes after they are formed on the promoter. In addition,
      DNA immunoprecipitation experiments indicate that T antigen is associated with
      the stabilized TBP-TFIIA complexes bound to the DNA. In this regard, it has
      previously been shown that T antigen interacts with TBP; in the present study, we
      show that T antigen also interacts with TFIIA in vitro. In testing the ability of
      T antigen to stabilize the TBP-TFIIA complex, we found that stabilization is
      highly sensitive to the specific sequence context of the TATA element. Previous
      studies showed that T antigen could activate simple promoters containing the TATA
      elements from the hsp70 and c-fos gene promoters but failed to significantly
      activate similar promoters containing the TATA elements from the promoters of the
      SV40 early and adenovirus E2a genes. We find that the ability to stabilize the
      TBP-TFIIA complex on the hsp70 and c-fos TATA elements, and not on the SV40 early
      and E2A TATA elements, correlates with the ability or inability to activate
      promoters containing these TATA elements.

PMID- 9632778
TI  - Rac regulates integrin-mediated spreading and increased adhesion of T
      lymphocytes.
AB  - Leukocyte adhesion to the extracellular matrix (ECM) is tightly controlled and is
      vital for the immune response. Circulating lymphocytes leave the bloodstream and
      adhere to ECM components at sites of inflammation and lymphoid tissues.
      Mechanisms for regulating T-lymphocyte-ECM adhesion include (i) an alteration in
      the affinity of cell surface integrin receptors for their extracellular ligands
      and (ii) an alteration of events following postreceptor occupancy (e.g., cell
      spreading). Whereas H-Ras and R-Ras were previously shown to affect T-cell
      adhesion by altering the affinity state of the integrin receptors, no signaling
      molecule has been identified for the second mechanism. In this study, we
      demonstrated that expression of an activated mutant of Rac triggered dramatic
      spreading of T cells and their increased adhesion on immobilized fibronectin in
      an integrin-dependent manner. This effect was not mimicked by expression of
      activated mutant forms of Rho, Cdc42, H-Ras, or ARF6, indicating the unique role
      of Rac in this event. The Rac-induced spreading was accompanied by specific
      cytoskeletal rearrangements. Also, a clustering of integrins at sites of cell
      adhesion and at the peripheral edges of spread cells was observed. We demonstrate
      that expression of RacV12 did not alter the level of expression of cell surface
      integrins or the affinity state of the integrin receptors. Moreover, our results
      indicate that Rac plays a role in the regulation of T-cell adhesion by a
      mechanism involving cell spreading, rather than by altering the level of
      expression or the affinity of the integrin receptors. Furthermore, we show that
      the Rac-mediated signaling pathway leading to spreading of T lymphocytes did not
      require activation of c-Jun kinase, serum response factor, or pp70(S6 kinase) but
      appeared to involve a phospholipid kinase.

PMID- 9632779
TI  - 14-3-3 facilitates Ras-dependent Raf-1 activation in vitro and in vivo.
AB  - 14-3-3 proteins complex with many signaling molecules, including the Raf-1
      kinase. However, the role of 14-3-3 in regulating Raf-1 activity is unclear. We
      show here that 14-3-3 is bound to Raf-1 in the cytosol but is totally displaced
      when Raf-1 is recruited to the plasma membrane by oncogenic mutant Ras, in vitro
      and in vivo. 14-3-3 is also displaced when Raf-1 is targeted to the plasma
      membrane. When serum-starved cells are stimulated with epidermal growth factor,
      some recruitment of 14-3-3 to the plasma membrane is evident, but 14-3-3
      recruitment correlates with Raf-1 dissociation and inactivation, not with Raf-1
      recruitment. In vivo, overexpression of 14-3-3 potentiates the specific activity
      of membrane-recruited Raf-1 without stably associating with the plasma membrane.
      In vitro, Raf-1 must be complexed with 14-3-3 for efficient recruitment and
      activation by oncogenic Ras. Recombinant 14-3-3 facilitates Raf-1 activation by
      membranes containing oncogenic Ras but reduces the amount of Raf-1 that
      associates with the membranes. These data demonstrate that the interaction of 14
      3-3 with Raf-1 is permissive for recruitment and activation by Ras, that 14-3-3
      is displaced upon membrane recruitment, and that 14-3-3 may recycle Raf-1 to the
      cytosol. A model that rationalizes many of the apparently discrepant observations
      on the role of 14-3-3 in Raf-1 activation is proposed.

PMID- 9632780
TI  - A novel phosphorylation-dependent RNase activity of GAP-SH3 binding protein: a
      potential link between signal transduction and RNA stability.
AB  - A potential p120 GTPase-activating protein (RasGAP) effector, G3BP (RasGAP Src
      homology 3 [SH3] binding protein), was previously identified based on its ability
      to bind the SH3 domain of RasGAP. Here we show that G3BP colocalizes and
      physically interacts with RasGAP at the plasma membrane of serum-stimulated but
      not quiescent Chinese hamster lung fibroblasts. In quiescent cells, G3BP was
      hyperphosphorylated on serine residues, and this modification was essential for
      its activity. Indeed, G3BP harbors a phosphorylation-dependent RNase activity
      which specifically cleaves the 3'-untranslated region of human c-myc mRNA. The
      endoribonuclease activity of G3BP can initiate mRNA degradation and therefore
      represents a link between a RasGAP-mediated signaling pathway and RNA turnover.

PMID- 9632781
TI  - Binding of Shp2 tyrosine phosphatase to FRS2 is essential for fibroblast growth
      factor-induced PC12 cell differentiation.
AB  - FRS2 is a lipid-anchored docking protein that plays an important role in linking
      fibroblast growth factor (FGF) and nerve growth factor receptors with the
      Ras/mitogen-activated protein (MAP) kinase signaling pathway. In this report, we
      demonstrate that FRS2 forms a complex with the N-terminal SH2 domain of the
      protein tyrosine phosphatase Shp2 in response to FGF stimulation. FGF stimulation
      induces tyrosine phosphorylation of Shp2, leading to the formation of a complex
      containing Grb2 and Sos1 molecules. In addition, a mutant FRS2 deficient in both
      Grb2 and Shp2 binding induces a weak and transient MAP kinase response and fails
      to induce PC12 cell differentiation in response to FGF stimulation. Furthermore,
      FGF is unable to induce differentiation of PC12 cells expressing an FRS2 point
      mutant deficient in Shp2 binding. Finally, we demonstrate that the catalytic
      activity of Shp2 is essential for sustained activation of MAP kinase and for
      potentiation of FGF-induced PC12 cell differentiation. These experiments
      demonstrate that FRS2 recruits Grb2 molecules both directly and indirectly via
      complex formation with Shp2 and that Shp2 plays an important role in FGF-induced
      PC12 cell differentiation.

PMID- 9632783
TI  - Interaction between major nitrogen regulatory protein NIT2 and pathway-specific
      regulatory factor NIT4 is required for their synergistic activation of gene
      expression in Neurospora crassa.
AB  - In Neurospora crassa, the major nitrogen regulatory protein, NIT2, a member of
      the GATA family of transcription factors, controls positively the expression of
      numerous genes which specify nitrogen catabolic enzymes. Expression of the highly
      regulated structural gene nit-3, which encodes nitrate reductase, is dependent
      upon a synergistic interaction of NIT2 with a pathway-specific control protein,
      NIT4, a member of the GAL4 family of fungal regulatory factors. The NIT2 and NIT4
      proteins both bind at specific recognition elements in the nit-3 promoter, but,
      in addition, we show that a direct protein-protein interaction between NIT2 and
      NIT4 is essential for optimal expression of the nit-3 structural gene. Neurospora
      possesses at least five different GATA factors which control different areas of
      cellular function, but which have a similar DNA binding specificity.
      Significantly, only NIT2, of the several Neurospora GATA factors examined,
      interacts with NIT4. We propose that protein-protein interactions of the
      individual GATA factors with additional pathway-specific regulatory factors
      determine each of their specific regulatory functions.

PMID- 9632782
TI  - The Mdm2 oncoprotein interacts with the cell fate regulator Numb.
AB  - The Mdm2 oncoprotein is a well-known inhibitor of the p53 tumor suppressor, but
      it may also possess p53-independent activities. In search of such p53-independent
      activities, the yeast two-hybrid screen was employed to identify Mdm2-binding
      proteins. We report that in vitro and in transfected cells, Mdm2 can associate
      with Numb, a protein involved in the determination of cell fate. This association
      causes translocation of overexpressed Numb into the nucleus and leads to a
      reduction in overall cellular Numb levels. Through its interaction with Numb,
      Mdm2 may influence processes such as differentiation and survival. This could
      potentially contribute to the altered properties of tumor cells which overexpress
      Mdm2.

PMID- 9632785
TI  - RNA binding activity of heterodimeric splicing factor U2AF: at least one RS
      domain is required for high-affinity binding.
AB  - The pre-mRNA splicing factor U2AF (U2 small nuclear ribonucleoprotein particle
      [snRNP] auxiliary factor) plays a critical role in 3' splice site selection. U2AF
      binds site specifically to the intron pyrimidine tract between the branchpoint
      and the 3' splice site and targets U2 snRNP to the branch site at an early step
      in spliceosome assembly. Human U2AF is a heterodimer composed of large (hU2AF65)
      and small (hU2AF35) subunits. hU2AF65 contains an arginine-serine-rich (RS)
      domain and three RNA recognition motifs (RRMs). hU2AF35 has a degenerate RRM and
      a carboxyl-terminal RS domain. Genetic studies have recently shown that the RS
      domains on the Drosophila U2AF subunit homologs are each inessential and might
      have redundant functions in vivo. The site-specific pyrimidine tract binding
      activity of the U2AF heterodimer has previously been assigned to hU2AF65. While
      the requirement for the three RRMs on hU2AF65 is firmly established, a role for
      the large-subunit RS domain in RNA binding remains unresolved. We have analyzed
      the RNA binding activity of the U2AF heterodimer in vitro. When the Drosophila
      small-subunit homolog (dU2AF38) was complexed with the large-subunit (dU2AF50)
      pyrimidine tract, RNA binding activity increased 20-fold over that of free
      dU2AF50. We detected a similar increase in RNA binding activity when we compared
      the human U2AF heterodimer and hU2AF65. Surprisingly, the RS domain on dU2AF38
      was necessary for the increased binding activity of the dU2AF heterodimer. In
      addition, removal of the RS domain from the Drosophila large-subunit monomer
      (dU2AF50DeltaRS) severely impaired its binding activity. However, if the dU2AF38
      RS domain was supplied in a complex with dU2AF50DeltaRS, high-affinity binding
      was restored. These results suggest that the presence of one RS domain of U2AF,
      on either the large or small subunit, promotes high-affinity pyrimidine tract RNA
      binding activity, consistent with redundant roles for the U2AF RS domains in
      vivo.

PMID- 9632784
TI  - In vitro genetic analysis of the RNA binding site of vigilin, a multi-KH-domain
      protein.
AB  - The function(s) and RNA binding properties of vigilin, a ubiquitous protein with
      14 KH domains, remain largely obscure. We recently showed that vigilin is the
      estrogen-inducible protein in polysome extracts which binds specifically to a
      segment of the 3' untranslated region (UTR) of estrogen-stabilized vitellogenin
      mRNA. In order to identify consensus mRNA sequences and structures important in
      binding of vigilin to RNA, before vigilin was purified, we developed a modified
      in vitro genetic selection protocol. We subsequently validated our selection
      procedure, which employed crude polysome extracts, by testing natural and in
      vitro-selected RNAs with purified recombinant vigilin. Most of the selected up
      binding mutants exhibited hypermutation of G residues leading to a largely
      unstructured, single-stranded region containing multiple conserved (A)nCU and
      UC(A)n motifs. All eight of the selected down-binding mutants contained a
      mutation in the sequence (A)nCU. Deletion analysis indicated that approximately
      75 nucleotides are required for maximal binding. Using this information, we
      predicted and subsequently identified a strong vigilin binding site near the 3'
      end of human dystrophin mRNA. RNA sequences from the 3' UTRs of transferrin
      receptor and estrogen receptor, which lack strong homology to the selected
      sequences, did not bind vigilin. These studies describe an aproach to identifying
      long RNA binding sites and describe sequence and structural requirements for
      interaction of vigilin with RNAs.

PMID- 9632786
TI  - Adenovirus E1B 19,000-molecular-weight protein activates c-Jun N-terminal kinase
      and c-Jun-mediated transcription.
AB  - Adenovirus E1B proteins (19,000-molecular-weight [19K] and 55K proteins) inhibit
      apoptosis and cooperate with adenovirus E1A to induce full oncogenic
      transformation of primary cells. The E1B 19K protein has previously been shown to
      be capable of activating transcription; however, the underlying mechanisms are
      unclear. Here, we show that adenovirus infection activates the c-Jun N-terminal
      kinase (JNK) and that the E1B gene products are necessary for adenovirus to
      activate JNK. In transfection assays, we show that the E1B 19K protein is
      sufficient to activate JNK and can strongly induce c-Jun-dependent transcription.
      Mapping studies show that the C-terminal portion of E1B 19K is necessary for
      induction of c-Jun-mediated transcription. Using dominant-negative mutants of
      several kinases upstream of JNK, we show that MEKK1 and MKK4, but not Ras, are
      involved in the induction of JNK activity by adenovirus infection. The same
      dominant-negative kinase mutants also block the ability of E1B 19K to induce c
      Jun-mediated transcription. Taken together, these results suggest that E1B 19K
      may utilize the MEKK1-MKK4-JNK signaling pathway to activate c-Jun-dependent
      transcription and demonstrate a novel, kinase-activating activity of E1B 19K that
      may underlie its ability to regulate transcription.

PMID- 9632787
TI  - DA-complex assembly activity required for VP16C transcriptional activation.
AB  - One class of transcriptional activation domains stimulates the concerted binding
      of TFIIA and TFIID to promoter DNA. To test whether this DA-complex assembly
      activity contributes significantly to the overall mechanism of activation in
      vivo, we analyzed mutants of the 38-amino-acid residue VP16C activation subdomain
      from herpes simplex virus. An excellent correlation was observed between the in
      vivo activation function of these mutants and their in vitro DA-complex assembly
      activity. Mutants severely defective for in vivo activation also showed reduced
      in vitro binding to native TFIIA. No significant correlation between in vivo
      activation function and in vitro binding to human TATA binding protein, human
      TFIIB, or Drosophila melanogaster TAFII40 was observed for this set of VP16C
      mutants. These results argue that the ability of VP16C to increase the rate and
      extent of DA-complex assembly makes a significant contribution to the overall
      mechanism of transcriptional activation in vivo.

PMID- 9632788
TI  - Growth suppression by an E2F-binding-defective retinoblastoma protein (RB):
      contribution from the RB C pocket.
AB  - Growth suppression by the retinoblastoma protein (RB) is dependent on its ability
      to form complexes with transcription regulators. At least three distinct protein
      binding activities have been identified in RB: the large A/B pocket binds E2F,
      the A/B pocket binds the LXCXE peptide motif, and the C pocket binds the nuclear
      c-Abl tyrosine kinase. Substitution of Trp for Arg 661 in the B region of RB
      (mutant 661) inactivates both E2F and LXCXE binding. The tumor suppression
      function of mutant 661 is not abolished, because this allele predisposes its
      carriers to retinoblastoma development with a low penetrance. In cell-based
      assays, 661 is shown to inhibit G1/S progression. This low-penetrance mutant also
      induces terminal growth arrest with reduced but detectable activity. We have
      constructed mutations that disrupt C pocket activity. When overproduced, the RB C
      terminal fragment did not induce terminal growth arrest but could inhibit G1/S
      progression, and this activity was abolished by the C-pocket mutations. In full
      length RB, the C-pocket mutations reduced but did not abolish RB function.
      Interestingly, combination of the C-pocket and 661 mutations completely abolished
      RB's ability to cause an increase in the percentage of cells in G1 and to induce
      terminal growth arrest. These results suggest that the A/B or C region can induce
      a prolongation of G1 through mechanisms that are independent of each other. In
      contrast, long-term growth arrest requires combined activities from both regions
      of RB. In addition, E2F and LXCXE binding are not the only mechanisms through
      which RB inhibits cell growth. The C pocket also contributes to RB-mediated
      growth suppression.

PMID- 9632789
TI  - Prohibitin family members interact genetically with mitochondrial inheritance
      components in Saccharomyces cerevisiae.
AB  - Phb2p, a homolog of the tumor suppressor protein prohibitin, was identified in a
      genetic screen for suppressors of the loss of Mdm12p, a mitochondrial outer
      membrane protein required for normal mitochondrial morphology and inheritance in
      Saccharomyces cerevisiae. Phb2p and its homolog, prohibitin (Phb1p), were
      localized to the mitochondrial inner membrane and characterized as integral
      membrane proteins which depend on each other for their stability. In otherwise
      wild-type genetic backgrounds, null mutations in PHB1 and PHB2 did not confer any
      obvious phenotypes. However, loss of function of either PHB1 or PHB2 in cells
      with mitochondrial DNA deleted led to altered mitochondrial morphology, and phb1
      or phb2 mutations were synthetically lethal when combined with a mutation in any
      of three mitochondrial inheritance components of the mitochondrial outer
      membrane, Mdm12p, Mdm10p, and Mmm1p. These results provide the first evidence of
      a role for prohibitin in mitochondrial inheritance and in the regulation of
      mitochondrial morphology.

PMID- 9632790
TI  - Spa2p interacts with cell polarity proteins and signaling components involved in
      yeast cell morphogenesis.
AB  - The yeast protein Spa2p localizes to growth sites and is important for polarized
      morphogenesis during budding, mating, and pseudohyphal growth. To better
      understand the role of Spa2p in polarized growth, we analyzed regions of the
      protein important for its function and proteins that interact with Spa2p. Spa2p
      interacts with Pea2p and Bud6p (Aip3p) as determined by the two-hybrid system;
      all of these proteins exhibit similar localization patterns, and spa2Delta,
      pea2Delta, and bud6Delta mutants display similar phenotypes, suggesting that
      these three proteins are involved in the same biological processes.
      Coimmunoprecipitation experiments demonstrate that Spa2p and Pea2p are tightly
      associated with each other in vivo. Velocity sedimentation experiments suggest
      that a significant portion of Spa2p, Pea2p, and Bud6p cosediment, raising the
      possibility that these proteins form a large, 12S multiprotein complex. Bud6p has
      been shown previously to interact with actin, suggesting that the 12S complex
      functions to regulate the actin cytoskeleton. Deletion analysis revealed that
      multiple regions of Spa2p are involved in its localization to growth sites. One
      of the regions involved in Spa2p stability and localization interacts with Pea2p;
      this region contains a conserved domain, SHD-II. Although a portion of Spa2p is
      sufficient for localization of itself and Pea2p to growth sites, only the full
      length protein is capable of complementing spa2 mutant defects, suggesting that
      other regions are required for Spa2p function. By using the two-hybrid system,
      Spa2p and Bud6p were also found to interact with components of two mitogen
      activated protein kinase (MAPK) pathways important for polarized cell growth.
      Spa2p interacts with Ste11p (MAPK kinase [MEK] kinase) and Ste7p (MEK) of the
      mating signaling pathway as well as with the MEKs Mkk1p and Mkk2p of the Slt2p
      (Mpk1p) MAPK pathway; for both Mkk1p and Ste7p, the Spa2p-interacting region was
      mapped to the N-terminal putative regulatory domain. Bud6p interacts with Ste11p.
      The MEK-interacting region of Spa2p corresponds to the highly conserved SHD-I
      domain, which is shown to be important for mating and MAPK signaling. spa2
      mutants exhibit reduced levels of pheromone signaling and an elevated level of
      Slt2p kinase activity. We thus propose that Spa2p, Pea2p, and Bud6p function
      together, perhaps as a complex, to promote polarized morphogenesis through
      regulation of the actin cytoskeleton and signaling pathways.

PMID- 9632791
TI  - Analysis of gene targeting and intrachromosomal homologous recombination
      stimulated by genomic double-strand breaks in mouse embryonic stem cells.
AB  - To investigate the effects of in vivo genomic DNA double-strand breaks on the
      efficiency and mechanisms of gene targeting in mouse embryonic stem cells, we
      have used a series of insertion and replacement vectors carrying two, one, or no
      genomic sites for the rare-cutting endonuclease I-SceI. These vectors were
      introduced into the hypoxanthine phosphoribosyltransferase (hprt) gene to produce
      substrates for gene-targeting (plasmid-to-chromosome) or intrachromosomal (direct
      repeat) homologous recombination. Recombination at the hprt locus is markedly
      increased following transfection with an I-SceI expression plasmid and a
      homologous donor plasmid (if needed). The frequency of gene targeting in clones
      with an I-SceI site attains a value of 1%, 5,000-fold higher than that in clones
      with no I-SceI site. The use of silent restriction site polymorphisms indicates
      that the frequencies with which donor plasmid sequences replace the target
      chromosomal sequences decrease with distance from the genomic break site. The
      frequency of intrachromosomal recombination reaches a value of 3.1%, 120-fold
      higher than background spontaneous recombination. Because palindromic insertions
      were used as polymorphic markers, a significant number of recombinants exhibit
      distinct genotypic sectoring among daughter cells from a single clone, suggesting
      the existence of heteroduplex DNA in the original recombination product.

PMID- 9632792
TI  - Role of the PAS domain in regulation of dimerization and DNA binding specificity
      of the dioxin receptor.
AB  - The dioxin receptor is a ligand-regulated transcription factor that mediates
      signal transduction by dioxin and related environmental pollutants. The receptor
      belongs to the basic helix-loop-helix (bHLH)-Per-Arnt-Sim (PAS) family of
      factors, which, in addition to the bHLH motif, contain a PAS region of homology.
      Upon activation, the dioxin receptor dimerizes with the bHLH-PAS factor Arnt,
      enabling the receptor to recognize xenobiotic response elements in the vicinity
      of target genes. We have studied the role of the PAS domain in dimerization and
      DNA binding specificity of the dioxin receptor and Arnt by monitoring the
      abilities of the individual bHLH domains and different bHLH-PAS fragments to
      dimerize and bind DNA in vitro and recognize target genes in vivo. The minimal
      bHLH domain of the dioxin receptor formed homodimeric complexes, heterodimerized
      with full-length Arnt, and together with Arnt was sufficient for recognition of
      target DNA in vitro and in vivo. In a similar fashion, only the bHLH domain of
      Arnt was necessary for DNA binding specificity in the presence of the dioxin
      receptor bHLH domain. Moreover, the bHLH domain of the dioxin receptor displayed
      a broad dimerization potential, as manifested by complex formation with, e.g. ,
      the unrelated bHLH-Zip transcription factor USF. In contrast, a construct
      spanning the dioxin receptor bHLH domain and an N-terminal portion of the PAS
      domain failed to form homodimers and was capable of dimerizing only with Arnt.
      Thus, the PAS domain is essential to confer dimerization specificity of the
      dioxin receptor.

PMID- 9632793
TI  - Regulation of transcription by hypoxia requires a multiprotein complex that
      includes hypoxia-inducible factor 1, an adjacent transcription factor, and
      p300/CREB binding protein.
AB  - Molecular adaptation to hypoxia depends on the binding of hypoxia-inducible
      factor 1 (HIF-1) to cognate response elements in oxygen-regulated genes. In
      addition, adjacent sequences are required for hypoxia-inducible transcription. To
      investigate the mechanism of interaction between these cis-acting sequences, the
      multiprotein complex binding to the lactate dehydrogenase A (LDH-A) promoter was
      characterized. The involvement of HIF-1, CREB-1/ATF-1, and p300/CREB binding
      protein (CBP) was demonstrated by techniques documenting in vitro binding, in
      combination with transient transfections that test the in vivo functional
      importance of each protein. In both the LDH-A promoter and the erythropoietin 3'
      enhancer, formation of multiprotein complexes was analyzed by using biotinylated
      probes encompassing functionally critical cis-acting sequences. Strong binding of
      p300/CBP required interactions with multiple DNA binding proteins. Thus, the
      necessity of transcription factor binding sites adjacent to a HIF-1 site for
      hypoxically inducible transcription may be due to the requirement of p300 to
      interact with multiple transcription factors for high-affinity binding and
      activation of transcription. Since it has been found to interact with a wide
      range of transcription factors, p300 is likely to play a similar role in other
      genes, mediating interactions between DNA binding proteins, thereby activating
      stimulus-specific and tissue-specific gene transcription.

PMID- 9632795
TI  - Gab1 acts as an adapter molecule linking the cytokine receptor gp130 to ERK
      mitogen-activated protein kinase.
AB  - Gab1 has structural similarities with Drosophila DOS (daughter of sevenless),
      which is a substrate of the protein tyrosine phosphatase Corkscrew. Both Gab1 and
      DOS have a pleckstrin homology domain and tyrosine residues, potential binding
      sites for various SH2 domain-containing adapter molecules when they are
      phosphorylated. We found that Gab1 was tyrosine phosphorylated in response to
      various cytokines, such as interleukin-6 (IL-6), IL-3, alpha interferon (IFN
      alpha), and IFN-gamma. Upon the stimulation of IL-6 or IL-3, Gab1 was found to
      form a complex with phosphatidylinositol (PI)-3 kinase and SHP-2, a homolog of
      Corkscrew. Mutational analysis of gp130, the common subunit of IL-6 family
      cytokine receptors, revealed that neither tyrosine residues of gp130 nor its
      carboxy terminus was required for tyrosine phosphorylation of Gab1. Expression of
      Gab1 enhanced gp130-dependent mitogen-activated protein (MAP) kinase ERK2
      activation. A mutation of tyrosine 759, the SHP-2 binding site of gp130,
      abrogated the interactions of Gab1 with SHP-2 and PI-3 kinase as well as ERK2
      activation. Furthermore, ERK2 activation was inhibited by a dominant negative p85
      PI-3 kinase, wortmannin, or a dominant negative Ras. These observations suggest
      that Gab1 acts as an adapter molecule in transmitting signals to ERK MAP kinase
      for the cytokine receptor gp130 and that SHP-2, PI-3 kinase, and Ras are involved
      in Gab1-mediated ERK activation.

PMID- 9632794
TI  - Myb-related Schizosaccharomyces pombe cdc5p is structurally and functionally
      conserved in eukaryotes.
AB  - Schizosaccharomyces pombe cdc5p is a Myb-related protein that is essential for
      G2/M progression. To explore the structural and functional conservation of Cdc5
      throughout evolution, we isolated Cdc5-related genes and cDNAs from Saccharomyces
      cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, and Homo sapiens.
      Supporting the notion that these Cdc5 gene family members are functionally
      homologous to S. pombe cdc5(+), human and fly Cdc5 cDNAs are capable of
      complementing the temperature-sensitive lethality of the S. pombe cdc5-120
      mutant. Furthermore, S. cerevisiae CEF1 (S. cerevisiae homolog of cdc5(+)), like
      S. pombe cdc5(+), is essential during G2/M. The location of the cdc5-120
      mutation, as well as mutational analyses of Cef1p, indicate that the Myb repeats
      of cdc5p and Cef1p are important for their function in vivo. However, we found
      that unlike in c-Myb, single residue substitutions of glycines for hydrophobic
      residues within the Myb repeats of Cef1p, which are essential for maintaining
      structure of the Myb domain, did not impair Cef1p function in vivo. Rather,
      multiple W-to-G substitutions were required to inactivate Cef1p, and many of the
      substitution mutants were found to confer temperature sensitivity. Although it is
      possible that Cef1p acts as a transcriptional activator, we have demonstrated
      that Cef1p is not involved in transcriptional activation of a class of G2/M
      regulated genes typified by SWI5. Collectively, these results suggest that Cdc5
      family members participate in a novel pathway to regulate G2/M progression.

PMID- 9632796
TI  - Tumor-specific PAX3-FKHR transcription factor, but not PAX3, activates the
      platelet-derived growth factor alpha receptor.
AB  - The t(2;13) chromosomal translocation occurs at a high frequency in alveolar
      rhabdomyosarcoma, a common pediatric tumor of muscle. This translocation results
      in the production of a chimeric fusion protein derived from two developmentally
      regulated transcription factors, PAX3 and FKHR. The two DNA binding modules, the
      paired domain and the homeodomain, of PAX3 are fused in frame to the
      transactivation domain of FKHR. Previously, tumor-specific PAX3-FKHR has been
      shown to bind to DNA sequences normally recognized by wild-type PAX3 and to
      exhibit relatively enhanced transcriptional activity. The DNA binding sites used
      to demonstrate that PAX3-FKHR is a more potent transcriptional activator than
      PAX3 have included recognition sequences for the paired domain of PAX3. In this
      report, we demonstrate the ability of PAX3-FKHR to activate the product of a
      growth control gene, platelet-derived growth factor alpha receptor (PDGFalphaR),
      by recognizing a paired-type homeodomain binding site located in the PDGFalphaR
      promoter. PAX3 alone cannot mediate transcriptional activation of this promoter
      under the conditions tested. This provides the first evidence that chromosomal
      translocation results in altered target gene specificity of PAX3-FKHR and
      suggests a transcriptional target that may play a significant role in oncogenic
      activity and rhabdomyosarcoma development.

PMID- 9632797
TI  - Tyrosine 1101 of Tie2 is the major site of association of p85 and is required for
      activation of phosphatidylinositol 3-kinase and Akt.
AB  - Tie2 is an endothelium-specific receptor tyrosine kinase that is required for
      both normal embryonic vascular development and tumor angiogenesis and is thought
      to play a role in vascular maintenance. However, the signaling pathways
      responsible for the function of Tie2 remain unknown. In this report, we
      demonstrate that the p85 subunit of phosphatidylinositol 3-kinase (PI3-kinase)
      associates with Tie2 and that this association confers functional lipid kinase
      activity. Mutation of tyrosine 1101 of Tie2 abrogated p85 association both in
      vitro and in vivo in yeast. Tie2 was found to activate PI3-kinase in vivo as
      demonstrated by direct measurement of increases in cellular phosphatidylinositol
      3-phosphate and phosphatidylinositol 3, 4-bisphosphate, by plasma membrane
      translocation of a green fluorescent protein-Akt pleckstrin homology domain
      fusion protein, and by downstream activation of the Akt kinase. Activation of PI3
      kinase was abrogated in these assays by mutation of Y1101 to phenylalanine,
      consistent with a requirement for this residue for p85 association with Tie2.
      These results suggest that activation of PI3-kinase and Akt may in part account
      for Tie2's role in both embryonic vascular development and pathologic
      angiogenesis, and they are consistent with a role for Tie2 in endothelial cell
      survival.

PMID- 9632798
TI  - Functional conservation of the transportin nuclear import pathway in divergent
      organisms.
AB  - Human transportin1 (hTRN1) is the nuclear import receptor for a group of pre
      mRNA/mRNA-binding proteins (heterogeneous nuclear ribonucleoproteins [hnRNP])
      represented by hnRNP A1, which shuttle continuously between the nucleus and the
      cytoplasm. hTRN1 interacts with the M9 region of hnRNP A1, a 38-amino-acid domain
      rich in Gly, Ser, and Asn, and mediates the nuclear import of M9-bearing proteins
      in vitro. Saccharomyces cerevisiae transportin (yTRN; also known as YBR017c or
      Kap104p) has been identified and cloned. To understanding the nuclear import
      mediated by yTRN, we searched with a yeast two-hybrid system for proteins that
      interact with it. In an exhaustive screen of the S. cerevisiae genome, the most
      frequently selected open reading frame was the nuclear mRNA-binding protein,
      Nab2p. We delineated a ca.-50-amino-acid region in Nab2p, termed NAB35, which
      specifically binds yTRN and is similar to the M9 motif. NAB35 also interacts with
      hTRN1 and functions as a nuclear localization signal in mammalian cells.
      Interestingly, yTRN can also mediate the import of NAB35-bearing proteins into
      mammalian nuclei in vitro. We also report on additional substrates for TRN as
      well as sequences of Drosophila melanogaster, Xenopus laevis, and
      Schizosaccharomyces pombe TRNs. Together, these findings demonstrate that both
      the M9 signal and the nuclear import machinery utilized by the transportin
      pathway are conserved in evolution.

PMID- 9632799
TI  - cis-Acting signal for inheritance of imprinted DNA methylation patterns in the
      preimplantation mouse embryo.
AB  - The inheritance of gametic methylation patterns is a critical event in the
      imprinting of genes. In the case of the imprinted RSVIgmyc transgene, the
      methylation pattern in the unfertilized egg is maintained by the early mouse
      embryo, whereas the sperm's methylation pattern is lost in the early embryo. To
      investigate the cis-acting requirements for this preimplantation stage of genomic
      imprinting, we examined the fate of different RSVIgmyc methylation patterns,
      preimposed on RSVIgmyc and introduced into the mouse zygote by pronuclear
      injection. RSVIgmyc methylation patterns with a low percentage of methylated CpG
      dinucleotides, generated by using bacterial cytosine methylases with four-base
      recognition sequences, were lost in the early embryo. In contrast, methylation
      was maintained when all CpG dinucleotides were methylated with the bacterial SssI
      (CpG) methylase. This singular maintenance of RSVIgmyc methylation preimposed
      with SssI methylase appears to be specific to the early, undifferentiated embryo;
      differentiated NIH 3T3 fibroblasts transfected with methylated versions of
      RSVIgmyc maintained all methylation patterns, independent of the level of
      preimposed methylation. The methylation pattern of the RSVIgmyc allele in adult
      founder transgenic mice that was produced by pronuclear injection of an SssI
      methylated construct could not be distinguished from the maternal RSVIgmyc
      methylation pattern. Thus, a highly methylated allele in adult mice, normally
      generated by transmission of RSVIgmyc through the female germ line, was also
      produced in founder transgenic mice by bypassing gametogenesis and introducing a
      highly methylated RSVIgmyc into the mouse zygote. These results suggest that
      RSVIgmyc methylation itself is a cis-acting signal for the preimplantation
      maintenance of the oocyte's methylation pattern and, therefore, a cis-acting
      signal for RSVIgmyc imprinting. Furthermore, our inability to identify a sequence
      element within RSVIgmyc that was absolutely required for its imprinting suggests
      that the extent of RSVIgmyc methylation, rather than a particular pattern of
      methylation, is the principal feature of this imprinting signal.

PMID- 9632800
TI  - The C-terminal domain of Sin1 interacts with the SWI-SNF complex in yeast.
AB  - In the yeast Saccharomyces cerevisiae, the SWI-SNF complex has been proposed to
      antagonize the repressive effects of chromatin by disrupting nucleosomes. The SIN
      genes were identified as suppressors of defects in the SWI-SNF complex, and the
      SIN1 gene encodes an HMG1-like protein that has been proposed to be a component
      of chromatin. Specific mutations (sin mutations) in both histone H3 and H4 genes
      produce the same phenotypic effects as do mutations in the SIN1 gene. In this
      study, we demonstrate that Sin1 and the H3 and H4 histones interact genetically
      and that the C terminus of Sin1 physically associates with components of the SWI
      SNF complex. In addition, we demonstrate that this interaction is blocked in the
      full-length Sin1 protein by the N-terminal half of the protein. Based on these
      and additional results, we propose that Sin1 acts as a regulatable bridge between
      the SWI-SNF complex and the nucleosome.

PMID- 9632801
TI  - The capacity of polyomavirus enhancer binding protein 2alphaB (AML1/Cbfa2) to
      stimulate polyomavirus DNA replication is related to its affinity for the nuclear
      matrix.
AB  - The nuclear matrix is thought to play an important role in the DNA replication of
      eukaryotic cells, although direct evidence for such a role is still lacking. A
      nuclear matrix-associated transcription factor, polyomavirus (Py) enhancer
      binding protein 2alphaB1 (PEBP2alphaB1) (AML1/Cbfa2), was found to stimulate Py
      replication through its cognate binding site. The minimal replication activation
      domain (RAD) was identified between amino acid (aa) 302 and aa 371 by using a
      fusion protein containing the GAL4 DNA binding domain (GAL4-RAD). In addition,
      the region showed affinity for the nuclear matrix and, on the basis of
      competition studies, binding activity for one or more proteins involved in the
      initiation of Py DNA replication. A leukemogenic chimeric protein,
      AML1/ETO(MTG8), which does not contain this region of PEBP2alphaB1/AML1, was also
      localized in the nuclear matrix fraction and competed for nuclear matrix
      association with PEBP2alphaB1 and GAL4-RAD. Moreover, AML1/ETO inhibited Py DNA
      replication stimulated by PEBP2alphaB1 and GAL4-RAD. The inhibition was specific
      for replication mediated by PEBP2alphaB1 and GAL4-RAD, and proportional to the
      degree of loss of these activators from the nuclear matrix, suggesting a
      requirement for nuclear matrix targeting in the stimulation of Py DNA replication
      by RAD. These results are the first to suggest a molecular link between the
      initiation of DNA replication and the nuclear matrix compartment.

PMID- 9632802
TI  - Cyclin-dependent kinase inhibitor p21 modulates the DNA primer-template
      recognition complex.
AB  - The p21 protein, a cyclin-dependent kinase (CDK) inhibitor, is capable of binding
      to both cyclin-CDK and the proliferating cell nuclear antigen (PCNA). Through its
      binding to PCNA, p21 can regulate the function of PCNA differentially in
      replication and repair. To gain an understanding of the precise mechanism by
      which p21 affects PCNA function, we have designed a new assay for replication
      factor C (RFC)-catalyzed loading of PCNA onto DNA, a method that utilizes a
      primer-template DNA attached to agarose beads via biotin-streptavidin. Using this
      assay, we showed that RFC remains transiently associated with PCNA on the DNA
      after the loading reaction. Addition of p21 did not inhibit RFC-dependent PCNA
      loading; rather, p21 formed a stable complex with PCNA on the DNA. In contrast,
      the formation of a p21-PCNA complex on the DNA resulted in the displacement of
      RFC from the DNA. The nonhydrolyzable analogs of ATP, adenosine-5'-O-(3
      thiotriphosphate) (ATPgammaS) and adenyl-imidodiphosphate, each stabilized the
      primer recognition complex containing RFC and PCNA in the absence of p21. RFC in
      the ATPgammaS-activated complex was no longer displaced from the DNA by p21. We
      propose that p21 stimulates the dissociation of the RFC from the PCNA-DNA complex
      in a process that requires ATP hydrolysis and then inhibits subsequent PCNA
      dependent events in DNA replication. The data suggest that the conformation of
      RFC in the primer recognition complex might change on hydrolysis of ATP. We also
      suggest that the p21-PCNA complex that remains attached to DNA might function to
      tether cyclin-CDK complexes to specific regions of the genome.

PMID- 9632803
TI  - Developmental specificity of the interaction between the locus control region and
      embryonic or fetal globin genes in transgenic mice with an HS3 core deletion.
AB  - The human beta-globin locus control region (LCR) consists of five erythroid
      lineage-specific DNase I-hypersensitive sites (HSs) and is required for
      activation of the beta-globin locus chromatin domain and globin gene expression.
      Each DNase I-HS of the LCR consists of a highly conserved core element and
      flanking sequences. To analyze the functional role of the core elements of the
      HSs, we deleted a 234-bp fragment encompassing the core of HS3 (HS3c) from a beta
      globin locus residing on a 248-kb beta-locus yeast artificial chromosome and
      analyzed its function in F2 progeny of transgenic mice. Human epsilon-globin gene
      expression was absent at day 10 and severely reduced in the day 12 embryonic
      erythropoiesis of mice lacking HS3c. In contrast, gamma-globin gene expression
      was normal in embryonic erythropoiesis but it was absent in definitive
      erythropoiesis in the fetal liver. These results indicate that the core element
      of HS3 is necessary for epsilon-globin gene transcription in embryonic cells and
      for gamma-globin gene transcription in definitive cells. Normal gamma-globin gene
      expression in embryonic cells and the absence of gamma-globin gene expression in
      definitive cells show that different HSs interact with gamma-globin gene
      promoters in these two stages of development. Such results provide direct
      evidence for developmental stage specificity of the interactions between the core
      elements of HSs and the promoters of the globin genes.

PMID- 9632804
TI  - Two domains unique to osteoblast-specific transcription factor Osf2/Cbfa1
      contribute to its transactivation function and its inability to heterodimerize
      with Cbfbeta.
AB  - Osf2/Cbfa1, hereafter called Osf2, is a member of the Runt-related family of
      transcription factors that plays a critical role during osteoblast
      differentiation. Like all Runt-related proteins, it contains a runt domain, which
      is the DNA-binding domain, and a C-terminal proline-serine-threonine-rich (PST)
      domain thought to be the transcription activation domain. Additionally, Osf2 has
      two amino-terminal domains distinct from any other Runt-related protein. To
      understand the mechanisms of osteoblast gene regulation by Osf2, we performed an
      extensive structure-function analysis. After defining a short Myc-related nuclear
      localization signal, a deletion analysis revealed the existence of three
      transcription activation domains and one repression domain. AD1 (for activation
      domain 1) comprises the first 19 amino acids of the molecule, which form the
      first domain unique to Osf2, AD2 is formed by the glutamine-alanine (QA) domain,
      the second domain unique to Osf2, and AD3 is located in the N-terminal half of
      the PST domain and also contains sequences unique to Osf2. The transcription
      repression domain comprises the C-terminal 154 amino acids of Osf2. DNA-binding,
      domain-swapping, and protein interaction experiments demonstrated that full
      length Osf2 does not interact with Cbfbeta, a known partner of Runt-related
      proteins, whereas a deletion mutant of Osf2 containing only the runt and PST
      domains does. The QA domain appears to be responsible for preventing this
      heterodimerization. Thus, our results uncover the unique functional organization
      of Osf2 by identifying functional domains not shared with other Runt-related
      proteins that largely control its transactivation and heterodimerization
      abilities.

PMID- 9632805
TI  - The Syk protein tyrosine kinase is essential for Fcgamma receptor signaling in
      macrophages and neutrophils.
AB  - The cytoplasmic protein tyrosine kinase Syk has two amino-terminal SH2 domains
      that engage phosphorylated immunoreceptor tyrosine-based activation motifs in the
      signaling subunits of immunoreceptors. Syk, in conjunction with Src family
      kinases, has been implicated in immunoreceptor signaling in both lymphoid and
      myeloid cells. We have investigated the role of Syk in Fcgamma receptor
      (FcgammaR)-dependent and -independent responses in bone marrow-derived
      macrophages and neutrophils by using mouse radiation chimeras reconstituted with
      fetal liver cells from Syk-/- embryos. Chimeric mice developed an abdominal
      hemorrhage starting 2 to 3 months after transplantation that was ultimately
      lethal. Syk-deficient neutrophils derived from the bone marrow were incapable of
      generating reactive oxygen intermediates in response to FcgammaR engagement but
      responded normally to tetradecanoyl phorbol acetate stimulation. Syk-deficient
      macrophages were defective in phagocytosis induced by FcgammaR but showed normal
      phagocytosis in response to complement. The tyrosine phosphorylation of multiple
      cellular polypeptides, including the FcgammaR gamma chain, as well as Erk2
      activation, was compromised in Syk-/- macrophages after FcgammaR stimulation. In
      contrast, the induction of nitric oxide synthase in macrophages stimulated with
      lipopolysaccharide and gamma interferon was not dependent on Syk. Surprisingly,
      Syk-deficient macrophages were impaired in the ability to survive or proliferate
      on plastic petri dishes. Taken together, these results suggest that Syk has
      specific physiological roles in signaling from FcgammaRs in neutrophils and
      macrophages and raise the possibility that in vivo, Syk is involved in signaling
      events other than those mediated by immunoreceptors.

PMID- 9632807
TI  - BAZF, a novel Bcl6 homolog, functions as a transcriptional repressor.
AB  - The BCL6 gene, which has been identified from the chromosomal translocation
      breakpoint in B-cell lymphomas, functions as a sequence-specific transcriptional
      repressor. We cloned a novel Bcl6-homologous gene, BAZF (encoding Bcl6-associated
      zinc finger protein). The predicted amino acid sequence of BAZF indicated that
      the BTB/POZ domain and the five repeats of the Kruppel-like zinc finger motif are
      located in the NH2-terminal region and the COOH-terminal region, respectively.
      BAZF associated with Bcl6 at the BTB/POZ domain and localized in the nucleus.
      Since zinc finger motifs of BAZF were 94% identical to those of Bcl6 at the amino
      acid level, BAZF bound specifically to the DNA-binding sequence of Bcl6 and
      functioned as a transcriptional repressor. The repressor activity was associated
      with both the BTB/POZ domain and the middle portion of BAZF. The 17-amino-acid
      sequence in the middle portion was completely conserved between BAZF and Bcl6,
      and the conserved region was critical for the repressor activity. Expression of
      BAZF mRNA, like that of Bcl6 mRNA, was induced in activated lymphocytes as an
      immediate-early gene. Therefore, the biochemical character of BAZF is similar to
      that of Bcl6 although the tissue expression pattern of BAZF differs from that of
      Bcl6. This is apparently the first report of a gene family whose members encode
      zinc finger proteins with the BTB/POZ domain.

PMID- 9632806
TI  - DNA-dependent protein kinase phosphorylation of IkappaB alpha and IkappaB beta
      regulates NF-kappaB DNA binding properties.
AB  - Regulation of the IkappaB alpha and IkappaB beta proteins is critical for
      modulating NF-kappaB-directed gene expression. Both IkappaB alpha and IkappaB
      beta are substrates for cellular kinases that phosphorylate the amino and carboxy
      termini of these proteins and regulate their function. In this study, we utilized
      a biochemical fractionation scheme to purify a kinase activity which
      phosphorylates residues in the amino and carboxy termini of both IkappaB alpha
      and IkappaB beta. Peptide microsequence analysis by capillary high-performance
      liquid chromatography ion trap mass spectroscopy revealed that this kinase was
      the DNA-dependent protein kinase catalytic subunit (DNA-PKcs). DNA-PK
      phosphorylates serine residue 36 but not serine residue 32 in the amino terminus
      of IkappaB alpha and also phosphorylates threonine residue 273 in the carboxy
      terminus of this protein. To determine the biological relevance of DNA-PK
      phosphorylation of IkappaB alpha, murine severe combined immunodeficiency (SCID)
      cell lines which lack the DNA-PKcs gene were analyzed. Gel retardation analysis
      using extract prepared from these cells demonstrated constitutive nuclear NF
      kappaB DNA binding activity, which was not detected in extracts prepared from
      SCID cells complemented with the human DNA-PKcs gene. Furthermore, IkappaB alpha
      that was phosphorylated by DNA-PK was a more potent inhibitor of NF-kappaB
      binding than nonphosphorylated IkappaB alpha. These results suggest that DNA-PK
      phosphorylation of IkappaB alpha increases its interaction with NF-kappaB to
      reduce NF-kappaB DNA binding properties.

PMID- 9632808
TI  - Targeted disruption of the gene encoding hepatocyte nuclear factor 3gamma results
      in reduced transcription of hepatocyte-specific genes.
AB  - The winged helix transcription factor hepatocyte nuclear factor 3gamma
      (HNF3gamma) is expressed in embryonic endoderm and its derivatives liver,
      pancreas, stomach, and intestine, as well as in testis and ovary. We have
      generated mice carrying an Hnf3g-lacZ fusion which deletes most of the HNF3gamma
      coding sequence as well as 5.5 kb of 3' flanking region. Mice homozygous for the
      mutation are fertile, develop normally, and show no morphological defects. The
      mild phenotype change of the Hnf3g-/- mice can be explained in part by an
      upregulation of HNF3alpha and HNF3beta in the liver of the mutant animals.
      Analysis of steady-state mRNA levels as well as transcription rates showed that
      levels of expression of several HNF3 target genes (phosphoenolpyruvate
      carboxykinase, transferrin, tyrosine aminotransferase) were reduced by 50 to 70%,
      indicating that HNF3gamma is an important activator of these genes in vivo.

PMID- 9632809
TI  - Cytoplasmic sequestration of the polyomavirus enhancer binding protein 2
      (PEBP2)/core binding factor alpha (CBFalpha) subunit by the leukemia-related
      PEBP2/CBFbeta-SMMHC fusion protein inhibits PEBP2/CBF-mediated transactivation.
AB  - The polyomavirus enhancer binding protein 2 (PEBP2)/core binding factor (CBF) is
      a transcription factor composed of two subunits, alpha and beta. The gene
      encoding the beta subunit is disrupted by inv(16), resulting in the formation of
      a chimeric protein, beta-SMMHC, which is associated with acute myelogenous
      leukemia. To understand the effect of beta-SMMHC on PEBP2-mediated
      transactivation, we used a luciferase assay system in which contribution of both
      the alpha and beta subunits was absolutely required to activate transcription.
      Using this system, we found that the minimal region of the beta subunit required
      for transactivation resides between amino acid 1 and 135, which is known to
      dimerize with the alpha subunit. In contrast, beta-SMMHC, despite having this
      minimal region for dimerization and transactivation, failed to support
      transcription with the alpha subunit. Furthermore beta-SMMHC blocked the
      synergistic transcription achieved by PEBP2 and CCAAT/enhancer binding protein
      alpha. By using a construct in which the PEBP2 alpha subunit was fused to the
      glucocorticoid receptor ligand binding domain, we demonstrated that coexpressed
      beta-SMMHC tightly sequestered the alpha subunit in the cytoplasm and blocked
      dexamethasone-dependent nuclear translocation of the alpha subunit. Thus, the
      result suggess that beta-SMMHC inhibits PEBP2-mediated transcription via
      cytoplasmic sequestration of the alpha subunit. Lastly proliferation of ME-1
      cells that harbor inv(16) was blocked by an antisense oligonucleotide
      complementary to the junction of the chimeric mRNA, suggesting that beta-SMMHC
      contributes to leukemogenesis by blocking the differentiation of myeloid cells.

PMID- 9632811
TI  - Calcium and S100B regulation of p53-dependent cell growth arrest and apoptosis.
AB  - In glial C6 cells constitutively expressing wild-type p53, synthesis of the
      calcium-binding protein S100B is associated with cell density-dependent
      inhibition of growth and apoptosis in response to UV irradiation. A functional
      interaction between S100B and p53 was first demonstrated in p53-negative mouse
      embryo fibroblasts (MEF cells) by sequential transfection with the S100B and the
      temperature-sensitive p53Val135 genes. We show that in MEF cells expressing a low
      level of p53Val135, S100B cooperates with p53Val135 in triggering calcium
      dependent cell growth arrest and cell death in response to UV irradiation at the
      nonpermissive temperature (37.5 degreesC). Calcium-dependent growth arrest of MEF
      cells expressing S100B correlates with specific nuclear accumulation of the wild
      type p53Val135 conformational species. S100B modulation of wild-type p53Val135
      nuclear translocation and functions was confirmed with the rat embryo fibroblast
      (REF) cell line clone 6, which is transformed by oncogenic Ha-ras and
      overexpression of p53Val135. Ectopic expression of S100B in clone 6 cells
      restores contact inhibition of growth at 37.5 degreesC, which also correlates
      with nuclear accumulation of the wild-type p53Val135 conformational species.
      Moreover, a calcium ionophore mediates a reversible G1 arrest in S100B-expressing
      REF (S100B-REF) cells at 37.5 degreesC that is phenotypically indistinguishable
      from p53-mediated G1 arrest at the permissive temperature (32 degreesC). S100B
      REF cells proceeding from G1 underwent apoptosis in response to UV irradiation.
      Our data support a model in which calcium signaling and S100B cooperate with the
      p53 pathways of cell growth inhibition and apoptosis.

PMID- 9632810
TI  - Activated polo-like kinase Plx1 is required at multiple points during mitosis in
      Xenopus laevis.
AB  - Entry into mitosis depends upon activation of the dual-specificity phosphatase
      Cdc25C, which dephosphorylates and activates the cyclin B-Cdc2 complex. Previous
      work has shown that the Xenopus polo-like kinase Plx1 can phosphorylate and
      activate Cdc25C in vitro. In the work presented here, we demonstrate that Plx1 is
      activated in vivo during oocyte maturation with the same kinetics as Cdc25C.
      Microinjection of wild-type Plx1 into Xenopus oocytes accelerated the rate of
      activation of Cdc25C and cyclin B-Cdc2. Conversely, microinjection of either an
      antibody against Plx1 or kinase-dead Plx1 significantly inhibited the activation
      of Cdc25C and cyclin B-Cdc2. This effect could be reversed by injection of active
      Cdc25C, indicating that Plx1 is upstream of Cdc25C. However, injection of Cdc25C,
      which directly activates cyclin B-Cdc2, also caused activation of Plx1,
      suggesting that a positive feedback loop exists in the Plx1 activation pathway.
      Other experiments show that injection of Plx1 antibody into early embryos, which
      do not require Cdc25C for the activation of cyclin B-Cdc2, resulted in an arrest
      of cleavage that was associated with monopolar spindles. These results
      demonstrate that in Xenopus laevis, Plx1 plays important roles both in the
      activation of Cdc25C at the initiation of mitosis and in spindle assembly at late
      stages of mitosis.

PMID- 9632812
TI  - Involvement of prolonged ras activation in thrombopoietin-induced megakaryocytic
      differentiation of a human factor-dependent hematopoietic cell line.
AB  - Thrombopoietin (TPO) is a hematopoietic growth factor that plays fundamental
      roles is both megakaryopoiesis and thrombopoiesis through binding to its
      receptor, c-mpl. Although TPO has been shown to activate various types of
      intracellular signaling molecules, such as the Janus family of protein tyrosine
      kinases, signal transducers and activators of transcription (STATs), and ras, the
      precise mechanisms underlying TPO-induced proliferation and differentiation
      remain unknown. In an effort to clarify the mechanisms of TPO-induced
      proliferation and differentiation, c-mpl was introduced into F-36P, a human
      interleukin-3 (IL-3)-dependent erythroleukemia cell line, and the effects of TPO
      on the c-mpl-transfected F-36P (F-36P-mpl) cells were investigated. F-36P-mpl
      cells were found to proliferate and differentiate at a high rate into mature
      megakaryocytes in response to TPO. Dominant-negative (dn) forms of STAT1, STAT3,
      STAT5, and ras were inducibly expressed in F-36P-mpl cells, and their effects on
      TPO-induced proliferation and megakaryocytic differentiation were analyzed. Among
      these dn molecules, both dn ras and dn STAT5 reduced TPO- or IL-3-induced
      proliferation of F-36P-mpl cells by approximately 30%, and only dn ras could
      inhibit TPO-induced megakaryocytic differentiation. In accord with this result,
      overexpression of activated ras (H-rasG12V) for 5 days led to megakaryocytic
      differentiation of F-36P-mpl cells. In a time course analysis on H-rasG12V
      induced differentiation, activation of the ras pathway for 24 to 28 h was
      required and sufficient to induce megakaryocytic differentiation. Consistent with
      this result, the treatment of F-36P-mpl cells with TPO was able to induce
      prolonged activation of ras for more than 24 h, whereas IL-3 had only a transient
      effect. These results suggest that prolonged ras activation may be involved in
      TPO-induced megakaryocytic differentiation.

PMID- 9632813
TI  - Human cyclin K, a novel RNA polymerase II-associated cyclin possessing both
      carboxy-terminal domain kinase and Cdk-activating kinase activity.
AB  - The gene coding for human cyclin K was isolated as a CPR (cell-cycle progression
      restoration) gene by virtue of its ability to impart a Far- phenotype to the
      budding yeast Saccharomyces cerevisiae and to rescue the lethality of a deletion
      of the G1 cyclin genes CLN1, CLN2, and CLN3. The cyclin K gene encodes a 357
      amino-acid protein most closely related to human cyclins C and H, which have been
      proposed to play a role in regulating basal transcription through their
      association with and activation of cyclin-dependent kinases (Cdks) that
      phosphorylate the carboxyl-terminal domain (CTD) of the large subunit of RNA
      polymerase II (RNAP II). Murine and Drosophila melanogaster homologs of cyclin K
      have also been identified. Cyclin K mRNA is ubiquitously expressed in adult mouse
      and human tissues, but is most abundant in the developing germ cells of the adult
      testis and ovaries. Cyclin K is associated with potent CTD kinase and Cdk kinase
      (CAK) activity in vitro and coimmunoprecipitates with the large subunit of RNAP
      II. Thus, cyclin K represents a new member of the "transcription" cyclin family
      which may play a dual role in regulating Cdk and RNAP II activity.

PMID- 9632814
TI  - CCAAT/enhancer binding protein alpha is a regulatory switch sufficient for
      induction of granulocytic development from bipotential myeloid progenitors.
AB  - The transcription factor CCAAT/enhancer binding protein alpha (C/EBPalpha)
      regulates a number of myeloid cell-specific genes. To delineate the role of
      C/EBPalpha in human granulopoiesis, we studied its expression and function in
      human primary cells and bipotential (granulocytic/monocytic) myeloid cell lines.
      We show that the expression of C/EBPalpha initiates with the commitment of
      multipotential precursors to the myeloid lineage, is specifically upregulated
      during granulocytic differentiation, and is rapidly downregulated during the
      alternative monocytic pathway. Conditional expression of C/EBPalpha alone in
      stably transfected bipotential cells triggers neutrophilic differentiation,
      concomitant with upregulation of the granulocyte-specific granulocyte colony
      stimulating factor receptor and secondary granule protein genes. Moreover,
      induced expression of C/EBPalpha in bipotential precursors blocks their monocytic
      differentiation program. These results indicate that C/EBPalpha serves as a
      myeloid differentiation switch acting on bipotential precursors and directing
      them to mature to granulocytes.

PMID- 9632815
TI  - Interactions among Drosophila nuclear envelope proteins lamin, otefin, and YA.
AB  - The nuclear envelope plays many roles, including organizing nuclear structure and
      regulating nuclear events. Molecular associations of nuclear envelope proteins
      may contribute to the implementation of these functions. Lamin, otefin, and YA
      are the three Drosophila nuclear envelope proteins known in early embryos. We
      used the yeast two-hybrid system to explore the interactions between pairs of
      these proteins. The ubiquitous major lamina protein, lamin Dm, interacts with
      both otefin, a peripheral protein of the inner nuclear membrane, and YA, an
      essential, developmentally regulated protein of the nuclear lamina. In agreement
      with this interaction, lamin and otefin can be coimmunoprecipitated from the
      vesicle fraction of Drosophila embryos and colocalize in nuclear envelopes of
      Drosophila larval salivary gland nuclei. The two-hybrid system was further used
      to map the domains of interaction among lamin, otefin, and YA. Lamin's rod domain
      interacts with the complete otefin protein, with otefin's hydrophilic NH2
      terminal domain, and with two different fragments derived from this domain.
      Analogous probing of the interaction between lamin and YA showed that the lamin
      rod and tail plus part of its head domain are needed for interaction with full
      length YA in the two-hybrid system. YA's COOH-terminal region is necessary and
      sufficient for interaction with lamin. Our results suggest that interactions with
      lamin might mediate or stabilize the localization of otefin and YA in the nuclear
      lamina. They also suggest that the need for both otefin and lamin in mediating
      association of vesicles with chromatin might reflect the function of a protein
      complex that includes these two proteins.

PMID- 9632816
TI  - PEX12, the pathogenic gene of group III Zellweger syndrome: cDNA cloning by
      functional complementation on a CHO cell mutant, patient analysis, and
      characterization of PEX12p.
AB  - Rat PEX12 cDNA was isolated by functional complementation of peroxisome
      deficiency of a mutant CHO cell line, ZP109 (K. Okumoto, A. Bogaki, K. Tateishi,
      T. Tsukamoto, T. Osumi, N. Shimozawa, Y. Suzuki, T. Orii, and Y. Fujiki, Exp.
      Cell Res. 233:11-20, 1997), using a transient transfection assay and an ectopic,
      readily visible marker, green fluorescent protein. This cDNA encodes a 359-amino
      acid membrane protein of peroxisomes with two transmembrane segments and a
      cysteine-rich zinc finger, the RING motif. A stable transformant of ZP109 with
      the PEX12 was morphologically and biochemically restored for peroxisome
      biogenesis. Pex12p was shown by expression of bona fide as well as epitope-tagged
      Pex12p to expose both N- and C-terminal regions to the cytosol. Fibroblasts
      derived from patients with the peroxisome deficiency Zellweger syndrome of
      complementation group III (CG-III) were also complemented for peroxisome
      biogenesis with PEX12. Two unrelated patients of this group manifesting
      peroxisome deficiency disorders possessed homozygous, inactivating PEX12
      mutations: in one, Arg180Thr by one point mutation, and in the other, deletion of
      two nucleotides in codons for 291Asn and 292Ser, creating an apparently unchanged
      codon for Asn and a codon 292 for termination. These results indicate that the
      gene encoding peroxisome assembly factor Pex12p is a pathogenic gene of CG-III
      peroxisome deficiency. Moreover, truncation and site mutation studies, including
      patient PEX12 analysis, demonstrated that the cytoplasmically oriented N- and C
      terminal parts of Pex12p are essential for biological function.

PMID- 9632817
TI  - Extensive, nonrandom diversity of excision footprints generated by Ds-like
      transposon Ascot-1 suggests new parallels with V(D)J recombination.
AB  - Upon insertion, transposable elements can disrupt or alter gene function in
      various ways. Transposons moving through a cut-and-paste mechanism are in
      addition often mutagenic when excising because repair of the empty site seldom
      restores the original sequence. The characterization of numerous excision events
      in many eukaryotes indicates that transposon excision from a given site can
      generate a high degree of DNA sequence and phenotypic variation. Whether such
      variation is generated randomly remains largely to be determined. To this end, we
      have exploited a well-characterized system of genetic instability in the fungus
      Ascobolus immersus to perform an extensive study of excision events. We show that
      this system, which produces many phenotypically and genetically distinct
      derivatives, results from the excision of a novel Ds-like transposon, Ascot-1,
      from the spore color gene b2. A unique set of 48 molecularly distinct excision
      products were readily identified from a representative sample of excision
      derivatives. Products varied in their frequency of occurrence over 4 orders of
      magnitude, yet most showed small palindromic nucleotide additions. Based on these
      and other observations, compelling evidence was obtained for intermediate hairpin
      formation during the excision reaction and for strong biases in the subsequent
      processing steps at the empty site. Factors likely to be involved in these biases
      suggest new parallels between the excision reaction performed by transposons of
      the hAT family and V(D)J recombination. An evaluation of the contribution of
      small palindromic nucleotide additions produced by transposon excision to the
      spectrum of spontaneous mutations is also presented.

PMID- 9632818
TI  - Normal myeloid development requires both the glutamine-rich transactivation
      domain and the PEST region of transcription factor PU.1 but not the potent acidic
      transactivation domain.
AB  - Gene targeting of transcription factor PU.1 results in an early block to fetal
      hematopoiesis, with no detectable lymphoid or myeloid cells produced in mouse
      embryos. Furthermore, PU.1(-/-) embryonic stem (ES) cells fail to differentiate
      into Mac-1(+) and F4/80(+) macrophages in vitro. We have previously shown that a
      PU.1 transgene under the control of its own promoter restores the ability of PU.
      1(-/-) ES cells to differentiate into macrophages. In this study, we take
      advantage of our PU.1(-/-) ES cell rescue system to genetically test which
      previously identified PU.1 functional domains are necessary for the development
      of mature macrophages. PU.1 functional domains include multiple N-terminal acidic
      and glutamine-rich transactivation domains, a PEST domain, several serine
      phosphorylation sites, and a C-terminal Ets DNA binding domain, all delineated
      and characterized by using standard biochemical and transactivational assays. By
      using the production of mature macrophages as a functional readout in our assay
      system, we have established that the glutamine-rich transactivation domain, a
      portion of the PEST domain, and the DNA binding domain are required for
      myelopoiesis. Deletion of three acidic domains, which exhibit potent
      transactivation potential in vitro, had no effect on the ability of PU.1 to
      promote macrophage development. Furthermore, mutagenesis of four independent
      sites of serine phosphorylation also had no effect on myelopoiesis. Collectively,
      our results indicate that PU.1 interacts with important regulatory proteins
      during macrophage development via the glutamine-rich and PEST domains. The PU.1(
      /-) ES cell rescue system represents a powerful, in vitro strategy to
      functionally map domains of PU.1 essential for normal hematopoiesis and the
      generation of mature macrophages.

PMID- 9632819
TI  - Targeting to transcriptionally active loci by the hydrophilic N-terminal domain
      of Drosophila DNA topoisomerase I.
AB  - DNA topoisomerase I (topo I) from Drosophila melanogaster contains a
      nonconserved, hydrophilic N-terminal domain of about 430 residues upstream of the
      conserved core domains. Deletion of this N terminus did not affect the catalytic
      activity of topo I, while further removal of sequences into the conserved regions
      inactivated its enzymatic activity. We have investigated the cellular function of
      the Drosophila topo I N-terminal domain with top1-lacZ transgenes. There was at
      least one putative nuclear localization signal within the first 315 residues of
      the N-terminal domain that allows efficient import of the large chimeric proteins
      into Drosophila nuclei. The top1-lacZ fusion proteins colocalized with RNA
      polymerase II (pol II) at developmental puffs on the polytene chromosomes. Either
      topo I or the top1-lacZ fusion protein was colocalized with RNA pol II in some
      but not all of the nonpuff, interband loci. However, the fusion proteins as well
      as RNA pol II were recruited to heat shock puffs during heat treatment, and they
      returned to the developmental puffs after recovery from heat shock. By
      immunoprecipitation, we showed that two of the largest subunits of RNA pol II
      coprecipitated with the N-terminal 315-residue fusion protein by using antibodies
      against beta-galactosidase. These data suggest that the topo I fusion protein can
      be localized to the transcriptional complex on chromatin and that the N-terminal
      315 residues were sufficient to respond to cellular processes, especially during
      the reprogramming of gene expression.

PMID- 9632820
TI  - Positive and negative autoregulation of REB1 transcription in Saccharomyces
      cerevisiae.
AB  - Reb1p is a DNA binding protein of Saccharomyces cerevisiae that has been
      implicated in the activation of transcription by polymerase (Pol) II, in the
      termination of transcription by Pol I, and in the organization of nucleosomes.
      Studies of the transcriptional control of the REB1 gene have led us to identify
      three Reb1p binding sites in the 5' region of the its gene, termed A, B, and C,
      at positions -110, -80, and +30 with respect to transcription initiation. In
      vitro, Reb1p binds to the three sites with the relative affinity of A >/= C > B.
      Kinetic parameters suggest that when both A and C sites are present on the same
      DNA molecule, the C site may recruit Reb1p for the A site. In vivo the A and B
      sites each contribute to the transcription activity of REB1 in roughly additive
      fashion. Mutation of both A and B sites abolishes transcription. On the other
      hand, the C site is a negative element, reducing transcription by 40%. In cells
      overexpressing Reb1p, the C site reduces transcription by more than 80%. This
      effect can be transposed to another transcription unit, demonstrating that the
      effect of Reb1p binding at the C site does not depend on interaction with
      upstream Reb1p molecules. Relocation of the C site to a position 105 bp
      downstream of the transcription initiation site abolishes its effect, suggesting
      that it does not act as a conventional attenuator of transcription. We conclude
      that binding of Reb1p at the C site hinders formation of the initiation complex.
      This arrangement of Reb1p binding sites provides a positive and negative
      mechanism to autoregulate the expression of REB1. Such an arrangement could serve
      to dampen the inevitable fluctuation in Rep1p levels caused by the intermittent
      presence of its mRNA within an individual cell.

PMID- 9632821
TI  - Transcriptional regulation of the MDR1 gene by histone acetyltransferase and
      deacetylase is mediated by NF-Y.
AB  - Recent studies have shown that the histone-modifying enzymes histone
      acetyltransferase (HAT) and histone deacetylase (HDAC) are involved in
      transcriptional activation and repression, respectively. However, little is known
      about the endogenous genes that are regulated by these enzymes or how specificity
      is achieved. In the present report, we demonstrate that HAT and HDAC activities
      modulate transcription of the P-glycoprotein-encoding gene, MDR1. Incubation of
      human colon carcinoma SW620 cells in 100-ng/ml trichostatin A (TSA), a specific
      HDAC inhibitor, increased the steady-state level of MDR1 mRNA 20-fold.
      Furthermore, TSA treatment of cells transfected with a wild-type MDR1
      promoter/luciferase construct resulted in a 10- to 15-fold induction of promoter
      activity. Deletion and point mutation analysis determined that an inverted CCAAT
      box was essential for this activation. Consistent with this observation,
      overexpression of p300/CREB binding protein-associated factor (P/CAF), a
      transcriptional coactivator with intrinsic HAT activity, activated the wild-type
      MDR1 promoter but not a promoter containing a mutation in the CCAAT box; deletion
      of the P/CAF HAT domain abolished activation. Gel shift and supershift analyses
      identified NF-Y as the CCAAT-box binding protein in these cells, and
      cotransfection of a dominant negative NF-Y expression vector decreased the
      activation of the MDR1 promoter by TSA. Moreover, NF-YA and P/CAF were shown to
      interact in vitro. This is the first report of a natural promoter that is
      modulated by HAT and HDAC activities in which the transcription factor mediating
      this regulation has been identified.

PMID- 9632822
TI  - Involvement of p53 and p21 in cellular defects and tumorigenesis in Atm-/- mice.
AB  - Disruption of the mouse Atm gene, whose human counterpart is consistently mutated
      in ataxia-telangiectasia (A-T) patients, creates an A-T mouse model exhibiting
      most of the A-T-related systematic and cellular defects. While ATM plays a major
      role in signaling the p53 response to DNA strand break damage, Atm-/- p53(-/-)
      mice develop lymphomas earlier than Atm-/- or p53(-/-) mice, indicating that
      mutations in these two genes lead to synergy in tumorigenesis. The cell cycle
      G1/S checkpoint is abolished in Atm-/- p53(-/-) mouse embryonic fibroblasts
      (MEFs) following gamma-irradiation, suggesting that the partial G1 cell cycle
      arrest in Atm-/- cells following gamma-irradiation is due to the residual p53
      response in these cells. In addition, the Atm-/- p21(-/-) MEFs are more severely
      defective in their cell cycle G1 arrest following gamma-irradiation than Atm-/-
      and p21(-/-) MEFs. The Atm-/- MEFs exhibit multiple cellular proliferative
      defects in culture, and an increased constitutive level of p21 in these cells
      might account for these cellular proliferation defects. Consistent with this
      notion, Atm-/- p21(-/-) MEFs proliferate similarly to wild-type MEFs and exhibit
      no premature senescence. These cellular proliferative defects are also rescued in
      Atm-/- p53(-/-) MEFs and little p21 can be detected in these cells, indicating
      that the abnormal p21 protein level in Atm-/- cells is also p53 dependent and
      leads to the cellular proliferative defects in these cells. However, the p21 mRNA
      level in Atm-/- MEFs is lower than that in Atm+/+ MEFs, suggesting that the
      higher level of constitutive p21 protein in Atm-/- MEFs is likely due to
      increased stability of the p21 protein.

PMID- 9632823
TI  - p48 Activates a UV-damaged-DNA binding factor and is defective in xeroderma
      pigmentosum group E cells that lack binding activity.
AB  - A subset of xeroderma pigmentosum (XP) group E cells lack a factor that binds to
      DNA damaged by UV radiation. This factor can be purified to homogeneity as p125,
      a 125-kDa polypeptide. However, when cDNA encoding p125 is translated in vitro,
      only a small fraction binds to UV-damaged DNA, suggesting that a second factor is
      required for the activation of p125. We discovered that most hamster cell lines
      expressed inactive p125, which was activated in somatic cell hybrids containing
      human chromosome region 11p11.2-11cen. This region excluded p125 but included
      p48, which encodes a 48-kDa polypeptide known to copurify with p125 under some
      conditions. Expression of human p48 activated p125 binding in hamster cells and
      increased p125 binding in human cells. No such effects were observed from
      expression of p48 containing single amino acid substitutions from XP group E
      cells that lacked binding activity, demonstrating that the p48 gene is defective
      in those cells. Activation of p125 occurred by a "hit-and-run" mechanism, since
      the presence of p48 was not required for subsequent binding. Nevertheless, p48
      was capable of forming a complex with p125 either bound to UV-damaged DNA or in
      free solution. It is notable that hamster cells fail to efficiently repair
      cyclobutane pyrimidine dimers in nontranscribed DNA and fail to express p48,
      which contains a WD motif with homology to proteins that reorganize chromatin. We
      propose that p48 plays a role in repairing lesions that would otherwise remain
      inaccessible in nontranscribed chromatin.

PMID- 9632825
TI  - Mapmerge: merge genomic maps.
AB  - MOTIVATION: When two or more genomic maps of a chromosomal region are available,
      it is useful to be able to synthesize them to create a merged map. RESULTS: We
      show that map merging is an exploratory process because there are multiple ways
      to combine data based upon what the user wishes to focus on, and upon which
      particular data subset emphasis is desired. We describe Mapmerge, a program for
      merging two genomic maps, discuss its limitations, and illustrate an example of
      its use. AVAILABILITY: Freely available (ANSI C source code, a Make file, test
      data files, documentation) on request from the author. CONTACT:
      Prakash.Nadkarni@yale.edu

PMID- 9632826
TI  - Automatic extraction of motifs represented in the hidden Markov model from a
      number of DNA sequences.
AB  - MOTIVATION: Automatic extraction of motifs that occur frequently on a set of
      unaligned DNA sequences is useful for predicting the binding sites of unknown
      transcription factors. Several programs for this purpose have been released.
      However, in our opinion, they are not practical enough to be applied to a large
      number of upstream sequences. RESULTS: We propose a new program called YEBIS (Yet
      another Environment for the analysis of BIopolymer Sequences) which is capable of
      extracting a set of motifs, without any a priori knowledge, from a number of
      functionally related DNA sequences. Using the hidden Markov model, these motifs
      are represented in a more general form than other conventional methods, such as
      the weight matrix method. When applied to several sets of benchmark data, it was
      found that YEBIS had comparable capability to the existing methods, but was much
      faster. Moreover, it could extract all known motifs from the LTR sequences (long
      terminal repeat sequences) in a single run. Finally, it could be successfully
      applied to approximately 400 human promoter sequences and some of the extracted
      motifs turned out to be known cis-elements. Therefore, YEBIS could be a practical
      tool for exploring the upstream sequences of genomic ORFs, some of which are
      regulated in a similar fashion. AVAILABILITY: YEBIS will be distributed to
      academic users free of charge. All requests should be sent to the address below.
      CONTACT: E-MAIL: yada@tokyo.jst.go.jp

PMID- 9632824
TI  - Studies of the interaction between Rad52 protein and the yeast single-stranded
      DNA binding protein RPA.
AB  - The RFA1 gene encodes the large subunit of the yeast trimeric single-stranded DNA
      binding protein replication protein A (RPA), which is known to play a critical
      role in DNA replication. A Saccharomyces cerevisiae strain carrying the rfa1-44
      allele displays a number of impaired recombination and repair phenotypes, all of
      which are suppressible by overexpression of RAD52. We demonstrate that a rad52
      mutation is epistatic to the rfa1-44 mutation, placing RFA1 and RAD52 in the same
      genetic pathway. Furthermore, two-hybrid analysis indicates the existence of
      interactions between Rad52 and all three subunits of RPA. The nature of this
      Rad52-RPA interaction was further explored by using two different mutant alleles
      of rad52. Both mutations lie in the amino terminus of Rad52, a region previously
      defined as being responsible for its DNA binding ability (U. H. Mortenson, C.
      Beudixen, I. Sunjeuaric, and R. Rothstein, Proc. Natl. Acad. Sci. USA 93:10729
      10734, 1996). The yeast two-hybrid system was used to monitor the protein-protein
      interactions of the mutant Rad52 proteins. Both of the mutant proteins are
      capable of self-interaction but are unable to interact with Rad51. The mutant
      proteins also lack the ability to interact with the large subunit of RPA, Rfa1.
      Interestingly, they retain their ability to interact with the medium-sized
      subunit, Rfa2. Given the location of the mutations in the DNA binding domain of
      Rad52, a model incorporating the role of DNA in the protein-protein interactions
      involved in the repair of DNA double-strand breaks is presented.

PMID- 9632827
TI  - DIAMOD: display and modeling of DNA bending.
AB  - MOTIVATION: DIAMOD (Displayandmodeling ofDNA) was created as a user-friendly
      software for exploring and better understanding DNA structural variations,
      particularly DNA bending. It was intended to be as open as possible so that any
      of the existing or future predictive models can be used with it. RESULTS: DIAMOD
      features graphic display and interactive manipulation of DNA molecules on the
      screen. Since it works with di-, tri- or tetranucleotide models supplied as
      external files of angular parameters, it was recently used to evaluate critically
      all available predictive models for DNA bending. The program has a unique option
      to insert bends at defined positions in DNA sequence independently of the
      currently used model, which enables the simulation of both intrinsic and protein
      induced kinking. Finally, many output file formats facilitate the sharing of data
      with other programs and the creation of visually pleasing images. AVAILABILITY:
      The program is available on request to academic users free of charge. It will be
      distributed via the WWW (http://www-personal.umich.edu/ mensur/software.html).
      Users with no network access can get a copy directly from the author. CONTACT:
      mensur@umich.edu

PMID- 9632828
TI  - Optimization of ribosomal RNA profile alignments.
AB  - MOTIVATION: Large alignments of ribosomal RNA sequences are maintained at various
      sites. New sequences are added to these alignments using a combination of manual
      and automatic methods. We examine the use of profile alignment methods for rRNA
      alignment and try to optimize the choice of parameters and sequence weights.
      RESULTS: Using a large alignment of eukaryotic SSU rRNA sequences as a test case,
      we empirically compared the performance of various sequence weighting schemes
      over a range of gap penalties. We developed a new weighting scheme which gives
      most weight to the sequences in the profile that are most similar to the new
      sequence. We show that it gives the most accurate alignments when combined with a
      more traditional sequence weighting scheme. AVAILABILITY: The source code of all
      software is freely available by anonymous ftp from chah.ucc.ie in the directory
      /home/ftp/pub/emmet,in the compressed file PRNAA.tar: CONTACT: emmet@chah.ucc.ie,
      des@chah.ucc.ie

PMID- 9632829
TI  - The new Virgil database: a service of rich links.
AB  - MOTIVATION: Links between biological objects are frequently used by researchers
      in biology. However, many of the links found in public databases are
      insufficiently documented and difficult to retrieve. Virgil introduces the idea
      of a rich link, i.e. the link itself and the related pieces of information.
      Virgil was developed to collect, manage and distribute such links. RESULTS: At
      the moment, Virgil is a prototype database that contains rich links between GDB
      genes and Genbank sequences. The Virgil data model is rich enough to describe
      comprehensively a link between two biological objects. Two different means to
      access the information were developed: a schema-driven Web interface and a CORBA
      server. AVAILABILITY: http://www.infobiogen. fr/services/virgil/home.html
      CONTACT: Frederic.Achard@infobiogen.fr

PMID- 9632830
TI  - Searching DNA databases for similarities to DNA sequences: when is a match
      significant?
AB  - MOTIVATION: Searching DNA sequences against a DNA database is an essential
      element of sequence analysis. However, few systematic studies have been carried
      out to determine when a match between two DNA sequences has biological
      significance and this is limiting the use that can be made of DNA searching
      algorithms. RESULTS: A test set of DNA sequences has been constructed consisting
      of artificially evolved and real sequences. This set has been used to test
      various database searching algorithms (BLAST, BLAST2, FASTA and Smith-Waterman)
      on a subset of the EMBL database. The results of this analysis have been used to
      determine the sensitivity and coverage of all of the algorithms. Guidelines have
      been produced which can be used to assess the significance of DNA database search
      results. The Smith-Waterman algorithm was shown to have the best coverage, but
      the worst sensitivity, whereas the default BLASTN algorithm (word length set to
      11) was shown to have good sensitivity, but poor coverage. A sensible compromise
      between speed, sensitivity and coverage can be obtained using either the FASTA or
      BLAST (word length set to 6) algorithms. However, analysis of the results also
      showed that no algorithm works well when the length of the probe sequence is <200
      bases. In general, matches can accurately be identified between coding regions of
      DNA sequences when there is >35% sequence identity between the corresponding
      proteins. Searching a DNA sequence against a DNA sequence database can,
      therefore, be a useful tool in sequence analysis. AVAILABILITY: The test sets
      used are available via anonymous ftp from mbisg2.sbc.man.ac.uk in the directory
      /pub/cabios/testdata/ CONTACT: I.Anderson@stud.man.ac.uk; abrass@man.ac.uk

PMID- 9632831
TI  - Comparative analysis of seven multiple protein sequence alignment servers: clues
      to enhance reliability of predictions.
AB  - MOTIVATION: The prediction reliability of seven multiple alignment servers
      currently available on the Internet (ClustalW, MAP, PIMA, Block Maker, MSA, MEME
      and Match-Box) has been evaluated in terms of power (sensitivity) and confidence
      (selectivity). Therefore, the alignments obtained have been respectively compared
      to refined structural alignments for 20 families of related proteins with low
      levels of identity. RESULTS: Results clearly show that any powerful method
      remains reliable when the rate of identity falls. For some methods, power and
      confidence decrease linearly with the rate of identity, while other methods
      emphasize reliability at the cost of a lower power. Increasing the number of
      related sequences included in the alignment may either improve or decrease the
      quality of the predictions substantially. For some methods, the gain in power or
      in confidence is quite systematic; for others, the effect of the addition of
      homologous sequences is highly unpredictable. Extracting the consensus between
      two different methods may increase the overall confidence of the predictions
      tremendously. Our conclusions induce users of sequence alignment methods on the
      Internet to select the most suitable technique according to their requirements in
      terms of selectivity and sensitivity. AVAILABILITY: The aligned sequences of the
      20 alignments of structure can be obtained automatically by sending the message
      'send: cabios_tests.txt' by e-mail to 'matchbox@biq.fundp.ac.be'. CONTACT:
      eric.depiereux@fundp.ac.be

PMID- 9632832
TI  - Frame: detection of genomic sequencing errors.
AB  - MOTIVATION: The underlying error rate for genomic sequencing sometimes results in
      the introduction of artificial frameshifts and in-frame stop codons into putative
      protein encoding genes. Severe errors are then introduced into the inferred
      transcripts through mis-translation or premature termination. RESULTS: We
      describe a system for screening segments of DNA for frameshift and in-frame stop
      errors in coding regions. The method is based on homology matching using blastx
      to compare all six reading frames of the query nucleotide sequence against
      selected protein sequence databases. Fragments of protein matching neighbouring
      regions of the query DNA are united and extended laterally to define candidate
      open reading frames, within which, frameshifts and stops are identified. Suitable
      targets include prokaryotic or other intron-free genomic sequence and
      complementary DNAs. As an example of its use, we report here two frameshifted
      ORFs that deviate from the original TIGR sequence annotations for the recently
      released Helicobacter pylori genome. AVAILABILITY: The tool is accessible via the
      URL http://www.sander.ebi.ac.uk/frame/. CONTACT: brown@ebi.ac.uk.

PMID- 9632833
TI  - GCUA: general codon usage analysis.
AB  - The program General Codon Usage Analysis (GCUA) has been developed for analysing
      codon and amino acid usage patterns. AVAILABILITY: ftp://ftp.nhm.ac.uk/pub/gcua.
      Freely available for academic use, commercial users should contact the author.
      CONTACT: J.McInerney@nhm.ac.uk

PMID- 9632834
TI  - POLINA: detection and evaluation of single amino acid substitutions in protein
      superfamilies.
AB  - MOTIVATION AND RESULTS: An algorithm is described for the quick identification
      and evaluation of amino acid substitutions in multiple protein sequence
      alignment. The strategy is based on the calculation of a relative conservation
      index for an amino acid at each position of the alignment. The algorithm is
      implemented in the computer program POLINA (Protein Oriented LINear Analysis)
      which provides a summary of analysis in a format suitable for import into a
      graphing program. AVAILABILITY: A copy of source code is available upon request
      from the authors or can be downloaded via the WWW at
      http://www.geocities.com/Athens/4654/POLINA.h tml. CONTACT: slevin@aecom.yu.edu;
      bsatir@aecom.yu.edu

PMID- 9632835
TI  - Self-organizing tree growing network for classifying amino acids.
AB  - A self-organizing tree growing neural network was applied to classify amino acids
      and amino acid exchange matrices. AVAILABILITY: SOTA, is freely available by
      anonymous FTP or at http://www.cnb.uam.es/bioinfo/Software/so ta. CONTACT:
      carazo@cnb.uam.es

PMID- 9632836
TI  - SOSUI: classification and secondary structure prediction system for membrane
      proteins.
AB  - The system SOSUI for the discrimination of membrane proteins and soluble ones
      together with the prediction of transmembrane helices was developed, in which the
      accuracy of the classification of proteins was 99% and the corresponding value
      for the transmembrane helix prediction was 97%. AVAILABILITY: The system SOSUI is
      available through internet access: http://www.tuat.ac.jp/mitaku/sosui/. CONTACT:
      sosui@biophys.bio.tuat. ac.jp.

PMID- 9632837
TI  - MView: a web-compatible database search or multiple alignment viewer.
AB  - MView is a tool for converting the results of a sequence database search into the
      form of a coloured multiple alignment of hits stacked against the query.
      Alternatively, an existing multiple alignment can be processed. In either case,
      the output is simply HTML, so the result is platform independent and does not
      require a separate application or applet to be loaded. AVAILABILITY: Free from
      http://www.sander.ebi.ac.uk/mview/ subject to copyright restrictions. CONTACT:
      brown@ebi.ac.uk

PMID- 9632838
TI  - The health consequences of vertebral deformity in elderly Chinese men and women.
AB  - The following health consequences of vertebral deformity in Hong Kong elderly
      Chinese men and women were studied: the prevalence of back pain, disability due
      to back pain, and low morale. Lateral X-ray films were taken of the thoracic and
      lumbar spine of 796 community-dwelling Chinese subjects (396 men, 400 women)
      (aged 70-79). Subjects with one or more definitely deformed vertebra (reduction
      in vertebral height 3 SD or more below the mean) were classified as definite
      cases, those with one or more mildly deformed vertebra (reduction in vertebral
      height 2-2.99 SD below the mean) as mild cases, and the rest as controls. The
      prevalence and consequences of back pain were measured by a standardized
      questionnaire, and morale was measured by the Geriatric Morale Score. The
      relative risk (RR) and 95% confidence interval (CI) of having back pain and being
      depressed were calculated by logistic regression. Classifications included 16% of
      men and 30% of women as definite cases, 37% of men and 35% of women as mild
      cases, and 47% of men and 35% of women as controls. The relative risk (RR) of
      back pain was 2.3 (95% CI 1.4-3.9) (P < 0.05) in women with definite deformity
      and 1.5 (95% CI 0.9-2.5) (P > 0.05) in women with mild deformity, as compared
      with controls. Sixty-four percent of all men had back pain. This prevalence was
      much higher than figures obtained in a previous survey on low back pain. The
      prevalence of back pain did not differ by deformity status, but more men with
      vertebral deformity were on analgesic. There was no significant association
      between disability due to back pain and vertebral deformity in women. The RR for
      having a low morale score (of 5 and below) was 2.3 (95% CI 1.3-4.1) (P < 0. 05)
      in women with mild deformity; men with vertebral deformity did not have a low
      morale. It was concluded that vertebral deformity was associated with significant
      back pain and psychological morbidity in elderly Chinese women. Although men with
      vertebral deformity did not report more back pain, more were on analgesics than
      controls.

PMID- 9632839
TI  - Genetic variation in alpha 2HS-glycoprotein is related to calcaneal broadband
      ultrasound attenuation in older women.
AB  - Calcaneal broadband ultrasound attenuation (BUA) is an independent predictor of
      hip and vertebral fractures. BUA is under genetic control, but the specific genes
      contributing to BUA are not well defined. We examined the relationship between
      genetic variation in alpha2HS-glycoprotein (AHSG), an abundant noncollagenous
      protein of bone matrix, and calcaneal BUA. Genetic polymorphism in AHSG was
      determined in 222 Caucasian women (age 66-92) enrolled in the Pittsburgh Study of
      Osteoporotic Fractures clinical center by isoelectric focusing of serum samples.
      Calcaneal BUA and bone mineral density (BMD) were measured on the same foot with
      a Walker Sonix UBA 575(+) and single X-ray absorptiometry. Hip and spine BMD were
      determined with a Hologic QDR-1000 densitometer using dual-energy X-ray
      absorptiometry. AHSG polymorphism was not significantly related to hip, lumbar
      spine, or calcaneal BMD. Compared with the homozygous AHSG*2 women, calcaneal BUA
      was 13% lower in heterozygous (P < 0.05) and 16% lower in homozygous AHSG*1 women
      (P < 0.05). This relationship persisted after controlling for age, weight,
      height, walks for exercise, and calcaneal BMD. Current and self-reported height
      were also lowest in homozygous AHSG*1 women, intermediate in heterozygous women,
      and highest among homozygous AHSG*2 subjects. These results suggest that the AHSG
      polymorphism may contribute to the genetic influence on calcaneal BUA and
      stature.

PMID- 9632840
TI  - Age-dependent effect of oral glucocorticoids on markers of bone resorption in
      patients with acute asthma.
AB  - It is generally accepted that bone formation is depressed during corticosteroid
      treatment, but the effects of glucocorticoids on bone resorption are less well
      characterized. We have investigated the effects of short-term treatment with high
      dose oral glucocorticoids on biochemical markers of bone turnover in 20
      consecutive patients with asthma who sought help for acute respiratory
      obstruction in our emergency department. Serum concentrations of the carboxy
      terminal cross-linked telopeptide of type 1 collagen (1CTP), reflecting bone
      resorption, and the carboxy-terminal propeptide of type 1 procollagen (P1CP),
      reflecting bone formation, were measured by radioimmunoassay. Changes of the
      circulating levels of the bone resorption marker 1CTP after treatment were age
      dependent with a significant negative correlation (r = -0.54, P = 0.01). The
      dependency on age remained when correcting, in a multiple linear regression
      analysis, for 1CTP levels at admission, weight, sex, and daily maintenance dose
      of inhaled glucocorticoids. Circulating levels of P1CP were suppressed in the
      whole group 1 week after initiation of glucocorticoid therapy, from 123.3 +/-
      10.2 ng/ml at admission to 88.1 +/- 6.3 ng/ml after 1 week (P < 0.01). The
      changes in P1CP levels were not related to age. Our data indicate that bone
      formation is suppressed by glucocorticoids in all age groups, whereas the effect
      of glucocorticoids on markers of bone resorption is dependent on age.

PMID- 9632841
TI  - Administration of a glucocorticoid with depot effect counteracts the stimulating
      effect of growth hormone on cancellous and cortical bone of the vertebral body in
      rats.
AB  - Our earlier studies have shown that growth hormone administration could not
      counteract decreased longitudinal growth and cortical osteopenia of rat femora
      induced by a glucocorticoid with depot effect. In the present study we examined
      the effects of glucocorticoid on vertebral bone as well as the effect of growth
      hormone on vertebral bone in young growing animals also given glucocorticoid
      injections. Five groups of female rats (3 1/2 months) were treated for 80 days as
      follows: (1) saline, (2) prednisolone: Delcortol 5 mg/kg/day, (3) growth hormone:
      5 mg/kg/day, (4) prednisolone and growth hormone, (5) food restriction. Vertebral
      dimensions, histomorphometry, and mechanical competence of the vertebral bone
      were examined. Growth hormone administration increased body weight, vertebral
      height, cross-sectional area, and volume. The compressive strength of the L4
      corpus cylinder was also increased due to an increase in cancellous bone volume
      and an increase in the area of cortical bone surrounding the vertebral body.
      Glucocorticoid administration decreased body weight, height, and volume of the
      intact vertebrae. Histological examination revealed that glucocorticoid
      administration decreased the area of cortical bone surrounding the vertebral body
      but had no effect on the cancellous bone volume. No effect of glucocorticoid
      administration on mechanical strength of the L4 corpus cylinder could be
      detected. In agreement with our findings in cortical bone, we found no effect of
      growth hormone on vertebral bone when given to animals also receiving
      glucocorticoid injections. Growth hormone increases longitudinal growth, cortical
      and cancellous bone mass, and mechanical competence of the vertebral body.
      Glucocorticoid administration decreases longitudinal growth of the vertebrae and
      cortical bone mass without affecting cancellous bone mass of the vertebral body.
      Despite this, administration of a glucocorticoid with depot effect totally
      inhibits the effect of growth hormone on vertebral bone.

PMID- 9632842
TI  - Protein kinase C modulates the synthesis of nitric oxide by osteoblasts.
AB  - To determine the involvement of protein kinase C (PKC) in nitric oxide (NO)
      synthesis of osteoblast, a combination of proinflammatory cytokines (tumor
      necrosis factor-alpha, interferon-gamma, bacterial lipopolysaccharide) were added
      on rat osteoblast-like cells. Results show that these cytokines clearly enhanced
      the synthesis of NO. The activation of PKC with phorbol ester also resulted in
      the stimulation of NO synthesis in these cells. These cytokines activated PKC and
      increased the levels of intracellular Ca2+. In addition, the cytokine-induced
      synthesis of NO was blocked by PKC inhibitors. Findings suggest the involvement
      of PKC in the synthesis of NO by rat osteoblasts.

PMID- 9632844
TI  - Stimulation of bone formation in vivo by insulin-like growth factor-II in rats.
AB  - Insulin-like growth factor-II (IGF-II) plays an important role in skeletal
      remodeling, however, little is known about its effect on bone formation in vivo.
      In our study of the stimulation of bone formation in vivo by IGF II we injected
      recombinant human IGF-II into the parietal bones of neonatal rats once a day for
      12 days. The bone mineral density measured by dual energy X-ray absorptiometry
      and the thickness of IGF-II-injected parietal bones increased in a dose-dependent
      manner. The layers of osteoblasts were observed along the IGF-II-injected side.

PMID- 9632843
TI  - Up-regulation of inducible nitric oxide (NO) synthase and NO production in HL-60
      cells stimulated to differentiate by phorbol 12-myristate 13-acetate plus 1,25
      dihydroxyvitamin D3 is not obtained with dimethylsulfoxide plus 1,25
      dihydroxyvitamin D3.
AB  - In previous studies we found that the calciotropic hormone 1,25-dihydroxyvitamin
      D3 [1,25(OH)2D3] augments the action of either prostaglandin E1 (PGE1) or NaF to
      induce differentiation of human promyelocytic HL-60 cells, a process that
      features increased generation of nitric oxide (NO) via up-regulation of inducible
      nitric oxide synthase (iNOS). We have now examined the short-term interaction of
      1,25(OH)2D3 with phorbol 12-myristate 13-acetate (PMA) and dimethylsulfoxide
      (DMSO) in these cells. PMA (100 nM) alone generally up-regulated several
      classical indices of macrophagic differentiation and stimulated cellular
      production of interleukin (IL)-1alpha, IL-6, tumor-necrosis factor (TNF)-alpha,
      PGE2, and NO. Increased generation of NO primarily resulted from increased
      expression of cellular iNOS. When 1,25(OH)2D3 (10 nM) was added to PMA
      treatments, most PMA-induced changes, particularly its effects to up-regulate
      iNOS-dependent NO production and change cell morphology, were multiplicatively
      augmented. In contrast, DMSO (1.3%) alone, an inducer of granulocytic
      differentiation, increased cytokine production, but failed to stimulate NO
      production or induce iNOS. In contrast to its striking interaction with PMA,
      1,25(OH)2D3 could not augment DMSO's differentiative effects. Changes in cellular
      cytokine production were eliminated as the driving force in HL-60 differentiation
      when specific neutralizing antibodies failed to produce any attenuation of iNOS
      up-regulation or of the shifts in cell morphology. However, indomethacin (30
      microM) blocked the synergistic interaction between 1,25(OH)2D3 + PMA to shift
      cell morphology and stimulate NO production. Subsequently adding PGE2 (1 ng/ml)
      to indomethacin-treated cells restored the ability of 1, 25(OH)2D3 + PMA to
      interactively increase cellular NO production, but failed to fully replicate the
      strong shift in cell morphology typical of PMA + 1,25(OH)2D3 treatments. Our
      findings suggest that interaction between 1,25(OH)2D3 and PMA to induce
      macrophagic differentiation increases iNOS-dependent NO production by a mechanism
      involving a cyclooxygenase product(s), possibly PGE2.

PMID- 9632845
TI  - Progesterone receptor A and B isoform expression in human osteoblasts.
AB  - We have previously shown that human progesterone receptors (PR) are expressed in
      human osteosarcoma cells and in primary human osteoblast cultures. The aim of
      this study was to examine PRa and PRb isoform expression in human osteosarcoma
      cells. In addition, the effect of beta-estradiol on PR promoter activity in three
      human osteosarcoma cell lines was analyzed. Rapid amplification of 5'cDNA ends
      (5'RACE) were used to detect PR mRNA transcripts coding for both PR isoforms in
      HOS-TE85, an early progenitor human osteosarcoma cell line. Analogous 5'RACE
      products were detected in the PR-positive breast-cancer cell line MCF-7. Southern
      blot analysis confirmed that the amplified products were PR specific. It was
      shown that the larger of two RACE products coded specifically for B isoform mRNA
      and that of the smaller product corresponded to a PRa specific transcript. No
      RACE products were detected in the PR-negative HeLa cell line. To determine if
      both PR promoters were active in osteoblasts, chimeric recombinants bearing the
      PRa (+464, +1105) and PRb (-711, +31) promoter regions subcloned into minimal
      pBLCAT vectors, were transiently expressed in three human osteosarcoma cell lines
      HOS-TE85, MG-63, and SAOS-2. It was shown that beta-estradiol induced both PRa
      and PRb promoter activity in all of the osteosarcoma cell lines examined. The
      finding that PRa and PRb mRNA transcripts are expressed in human osteoblasts, and
      that promoters for both isoforms are estrogen responsive provides further
      evidence that bone-forming cells are physiologically influenced by progesterone.

PMID- 9632846
TI  - Ultrastructural modifications of the extracellular matrix upon calcification of
      growth plate cartilage as revealed by quick-freeze deep etching technique.
AB  - The ultrastructural changes in cartilage matrix that occur during calcification
      have been examined in chick epiphyseal growth plate cartilage prepared by quick
      frozen, deep-etched, and rotary shadowed replicas. The extracellular cartilage
      matrix contains a reticular network closely associated with an extensive network
      of collagen. The components of the reticular network, including thick and thin
      filaments, are attached directly to the cell membrane, matrix vesicle membrane,
      and collagen fibrils. This network, which interconnects the matrix vesicles and
      collagen, fills the extracellular matrix. The dimensions of the reticular network
      seem to remain almost constant in size from the reserve and proliferative zones
      to the calcifying zone. The collagen fibrils seem to consist of subfibrillar
      structures that branch and anastomose. In optimally quick-frozen, deep-etched,
      prepared collagen, a cross-banding pattern was exposed. Globular structures stud
      the collagen fibrils, which gradually diminish in number from the reserve zone
      down to the calcifying zone. The matrix vesicles, when fractured, showed a
      granular appearance. In most cases, the fracture plane passed through the bilayer
      of the matrix vesicle membrane. The true surface of the matrix vesicle membrane,
      therefore, was exposed after deep etching. At the calcifying zone, crystal
      deposition had occurred in needle-like and/or plate-like form within the membrane
      bound matrix vesicles. The reticular network was still intact in the vicinity of
      the calcified matrix, but in the intercrystalline space, neither the reticular
      structure nor the globular structure was detectable. Within the calcified matrix,
      both reticular and granular structures had disappeared from the interfibrillar
      space of the collagen fibrils.

PMID- 9632847
TI  - The role of osteoblast density and endogenous interleukin-6 production in
      osteoclast formation from the hemopoietic stem cell line FDCP-MIX C2GM in
      coculture with primary osteoblasts.
AB  - Osteoclast formation from the hemopoietic stem cell line FDCP-mix C2GM was shown
      to be strongly dependent on osteoblast density. In cocultures of C2GM cells with
      fetal mouse osteoblasts seeded at high density (i.e., 2.5 x 10(4) cells/cm2), we
      found a significantly lower osteoclast formation compared with cocultures with
      osteoblasts seeded at low density (i.e., 1 x 10(4) cells/cm2). The
      differentiation state of osteoblasts in high-density cultures resembled more than
      that of osteoblasts in low-density cultures, the differentiation state of mature
      osteoblasts, since the cells in the former cultures showed higher alkaline
      phosphatase (APase) activity than the cells in the latter cultures, and nodules
      were formed in high-density cultures but not in low-density cultures. Endogenous
      interleukin-6 (IL-6) production was found to be significantly lower in high
      density cultures, which may partly explain the impaired osteoclast formation in
      high-density cocultures. Addition of IL-6 to the high-density cocultures indeed
      restored osteoclast formation. There appeared to be no overt difference in IL-6
      receptor mRNA expression between high-density and low-density cultures. In
      conclusion, this paper suggests that mature, highly differentiated osteoblasts
      are not directly involved in osteoclastogenesis. In contrast, osteoblast-like
      cells lacking mature osteoblast markers induce osteoclast formation. Whether
      these low-density osteoblast-like cells represent an immature differentiation
      state or the lining cell phenotype is unclear.

PMID- 9632848
TI  - Histopathological study of the role of CD4- and CD8-positive T cells on bone
      resorption induced by Escherichia coli endotoxin.
AB  - The purpose of this study was to clarify the involvement of CD4+ and CD8+ T cells
      on bone resorption induced by Escherichia coli endotoxin. Two kinds of monoclonal
      antibodies, anti-CD4 and/or anti-CD8, were employed for the depletion of each or
      both T cell subsets. E. coli endotoxin was injected into mouse mesial gingiva of
      the first molar of the left mandible every 48 hours for up to 14 days (7
      injections). The mice were divided into four groups: CD4-depleted, CD8-depleted,
      T cell-depleted, and normal. The mice were sacrificed on the day after the 1st,
      3rd, 4th, 5th, and 7th injection and alveolar bone was examined
      histopathologically and histomorphometrically. Bone surface in contact with
      osteoclasts was defined as the site of active resorption and the ratios of active
      resorption were compared among the four groups. In addition, sections obtained
      after the 1st, 4th, and 7th injection were immunohistologically stained in order
      to confirm the presence or absence of CD4+ or CD8+ T cells. Alveolar bone
      resorption gradually increased in normal mice as the number of injections
      increased. In contrast, alveolar bone resorption was significantly weaker in each
      or both subset-depleted mice. For the duration of the experimental period, the
      number of CD4+ T cells in CD8-depleted and normal mice significantly increased
      with increasing bone resorption. Considering the function of CD4+ and CD8+ T
      cells, these results suggest that each subset preferentially acts as a macrophage
      activator in the early period of bone resorption induced by E. coli endotoxin.

PMID- 9632849
TI  - The effect of trabecular structure on DXA-based predictions of bovine bone
      failure.
AB  - The objective of this study was to determine the influence of structural
      organization on the relationship between clinically assessed bone mineral density
      (BMD) and strength of trabecular bone. Accurate assessment of bone strength or
      fracture risk is a critical need as the population ages and the incidence of
      fractures increases. While ex vivo tests have demonstrated that BMD measured with
      dual-energy X-ray absorptiometry (DXA) correlates with failure load of whole
      bones, it is also known that the strength of trabecular bone cannot be explained
      by density alone. Cylindrical cores of bovine trabecular bone, harvested in a
      variety of orientations, were scanned with DXA to determine density, assessed
      with micro-MRI (magnetic resonance imaging) to measure orientation, and then
      loaded them to failure in bending. Measures of trabecular architecture included
      the angle between the specimen longitudinal (Z) axis and the principal material
      axis, the maximum mean intercept length (MILmax), the mean intercept length in
      the specimen primary axis (MILz), the degree of anisotropy, and the ratio between
      MILz and the length of the principal material axis. MILz was strongly associated
      with failure stress (r2 = 0.85, P < 0.001). BMD was also moderately associated
      with failure stress (r2 = 0.44, P = 0.004). Using a stepwise linear multiple
      regression analysis, the strongest predictor of failure stress was a combination
      of BMD, angle, and MILz (R2 = 0.91). When only longitudinal specimens were
      analyzed, the strongest predictor of failure stress was a combination of BMD and
      angle (R2 = 0.95). Therefore, trabecular orientation plays a significant and
      important role in failure of trabecular bone. Accounting for this may improve the
      associations between DXA-based density measures and patient fractures.

PMID- 9632850
TI  - Effects of high-fat diet on mature bone mineral content, structure, and
      mechanical properties.
AB  - Diets with a high saturated fat content can produce deleterious effects on the
      absorption of dietary calcium and consequently an adverse effect on bone
      mineralization in growing animals. Hence dietary fat may have long-term
      consequences for skeletal health and skeletal pathologies such as osteoporosis.
      Whether a diet high in saturated fat has similar negative effects on adult bone,
      however, remains unresolved. Thus, we investigated effects of a high-fat diet on
      mature bone structure and mechanics. Adult (40-week-old) roosters were maintained
      for 20 weeks on either a diet high in saturated fat (HF) or a low-fat (LF) diet.
      Cortical bone samples (tarsometatarsus) were tested mechanically in three-point
      bending, and cancellous bone cores from the femoral condyles and tibial plateau
      (four sites per knee) were tested mechanically in compression. Cortical bone
      cross-sectional areal data were also compared among the groups, and bone mineral
      content (BMC) was determined (by ashing) for both cortical bone and cancellous
      bone samples. There were no significant high-fat diet effects on mature cortical
      bone mechanical properties, geometric structure, or mineral content. Diet,
      however, did affect cancellous bone composition. For example, LF cancellous BMC
      was significantly greater than HF. Mechanical properties of the cancellous bone
      showed similar trends such that LF cancellous bone strength was consistently
      greater than HF. The potential for adverse effects of a HF diet on intestinal
      calcium absorption in the mature animal may be more apparent in cancellous bone,
      with its faster rate of turnover, than in cortical bone. Changes in cancellous
      bone structure and mechanical properties, related to dietary saturated fats, may
      have implications for understanding the role of nutrition in skeletal health and
      prevention of pathological bone loss (osteoporosis).

PMID- 9632851
TI  - A 12-month prospective study of the relationship between stress fractures and
      bone turnover in athletes.
AB  - Bone remodeling may be involved in the pathogenesis of stress fractures in
      athletes. We conducted a 12-month prospective study to evaluate bone turnover in
      46 female and 49 male track and field athletes aged 17-26 years (mean age 20.3;
      SD 2.0) 20 of whom developed a stress fracture. Baseline levels of bone turnover
      were evaluated in all athletes and monthly bone turnover levels were evaluated in
      a subset consisting of the 20 athletes who sustained a stress fracture and a
      matched comparison group who did not sustain a stress fracture. Bone formation
      was assessed using serum osteocalcin (OC) measured by human immunoradiometric
      assay and bone resorption by urinary excretion of pyridinium cross-links (Pyr and
      D-Pyr); high performance liquid chromatography and N-telopeptides of type 1
      collagen (NTx) using ELISA assay. Athletes who developed stress fractures had
      similar baseline levels of bone turnover compared with their nonstress fracture
      counterparts (P > 0.10). Results of serial measurements showed no differences in
      average levels of Pyr, D-Pyr, or OC in those who developed stress fractures (P =
      0.10) compared with the control group. In the athletes with stress fractures,
      there was also no difference in bone turnover levels prior to or following the
      onset of bony pain. Our results show that single and multiple measurements of
      bone turnover are not clinically useful in predicting the likelihood of stress
      fractures in athletes. Furthermore, there were no consistent temporal changes in
      bone turnover associated with stress fracture development. However, our results
      do not negate the possible pathogenetic role of local changes in bone remodeling
      at stress fracture sites, given the high biological variability of bone turnover
      markers and the fact that levels of bone turnover reflect the integration of all
      bone remodeling throughout the skeleton.

PMID- 9632853
TI  - Proceedings of the Annual Meeting of CIRSE London, United Kingdom, September 28
      October 2, 1997

PMID- 9632852
TI  - Differential effects of bone mineral content and bone area on vertebral strength
      in a swine model.
AB  - Since the biomechanical competence of a vertebral body may be closely related to
      the content and distribution of the bone mineral, we have evaluated the effects
      of projected vertebral bone area (BA) and bone mineral parameters [bone mineral
      content (BMC) or bone mineral density (BMD)] on their biomechanical competence.
      We used dual-energy X-ray absorptiometry (DXA) to assess the bone mineral
      parameters of 36 swine thoracic vertebrae (T1-T12) and 15 lumbar vertebrae (L1
      L5) after removal of the posterior elements. The failure load, compressive
      stress, and the stored strain energy of these vertebral bodies were assessed by a
      uniaxial compressive test using an MTS 810 testing system. Multiple regression
      analysis showed a significantly negative effect of BA and significantly positive
      effect of BMC on the biomechanical competence (compressive stress, r2 = 0.67, P <
      0.0001; failure load, r2 = 0.75, P < 0.0001). However, the stored strain energy
      was only related to the BMC (r2 = 0.35, P < 0.0001). The contributory effects of
      BMC and BA on the biomechanical competence were not equal. The effects of BMC was
      larger than BA in determining the failure load and stored strain energy, whereas
      the reverse was found for the compressive stress. Using the log-transformed
      parameters as the regressors resulted in similar results. These results suggested
      the differential effects of BA and BMC in determining the biomechanical
      competence of vertebral bodies. We recommend the use of both parameters instead
      of BMD alone for evaluation of the vertebral biomechanical competence.

PMID- 9632855
TI  - Announcements

PMID- 9632856
TI  - To the diagnostic surgical laparoscopist. Perhaps a greater calling.

PMID- 9632857
TI  - Emergency laparoscopy for abdominal stab wounds.
AB  - BACKGROUND: Management strategies for abdominal stab wounds (ASW) in initially
      asymptomatic patients range from mandatory explorative laparotomy (EL) to
      conservative approaches with observation alone. Emergency diagnostic laparoscopy
      (DL) may play a potential role between these two extremes-hence lowering the rate
      of unnecessary laparotomies and keeping the rate of missed injuries to a minimum.
      PATIENTS AND METHODS: At our institution mandatory EL was carried out in every
      patient with ASW until 1992. In a retrospective study the charts of 43 patients
      with ASW were reviewed in terms of initial diagnostic procedures, intraabdominal
      injuries, and course and length of hospital stay. Between 5/1993 and 4/1995 DL
      was performed in a prospective study in 15 patients with suspected peritoneal
      penetration (PP) after ASW according to a standardized diagnostic and therapeutic
      algorithm. RESULTS: In 17 patients (40%) EL showed no PP; 15 (35%) had
      significant intraabdominal injuries, while 11 patients with PP didn't have
      lacerations of intraabdominal organs, resulting in an overall rate of
      nontherapeutic laparotomy of 65%. Mortality was 6% (n = 3), average hospital stay
      8 days. Primary DL could exclude PP in 10 out of 15 patients (66%). The remaining
      five patients (33%) showed PP: In two patients with ASW to the right upper
      quadrant, intraabdominal injuries could be excluded by DL, and in one patient a
      low-grade liver injury was treated laparoscopically, thus avoiding laparotomy in
      a total of 87% (n = 13). In two patients with PP laparoscopy was converted to
      laparotomy: no pathological finding in one case, splenectomy for spleen
      laceration in the second patient, resulting in a rate of nontherapeutic
      laparotomies of 7%. All patients in this series had an uneventful course; average
      hospital stay was 2.4 days. CONCLUSIONS: DL offers an important diagnostic tool
      in excluding peritoneal penetration in ASW, hence lowering the rate of
      unnecessary laparotomies. Given experience and skills, laparoscopy may be used
      therapeutically in selected cases of ASW.

PMID- 9632858
TI  - The role of laparoscopy in the diagnosis and treatment of abdominal pain
      syndromes.
AB  - BACKGROUND: Diagnostic laparoscopy plays a significant role in the evaluation of
      acute and chronic abdominal pain in the era of therapeutic laparoscopic surgery.
      METHODS: We referred to our personal series of laparoscopy for both acute and
      chronic abdominal pain. This is a retrospective review of data accumulated
      prospectively between 1979 and the present. RESULTS: In our series, 387
      consecutive patients underwent laparoscopy because of abdominal pain. In a group
      of 121 patients with acute abdominal pain, a definitive diagnosis was made in 119
      cases (98%). Two patients needed laparotomy to confirm the diagnosis; both had a
      disease process that did not require laparotomy to treat. A definitive
      therapeutic laparoscopic procedure was performed in 53 cases 944%). In 45
      patients (38%), a diagnosis was made that did not require therapeutic laparoscopy
      or laparotomy to treat. In the remaining 21 patients (17.5%), exploratory
      laparotomy was needed to treat the condition. In a chronic abdominal pain group
      of 265 patients, the etiology was established laparoscopically in 201 cases
      (76%). A definitive therapeutic laparoscopic procedure was performed in 128
      patients (48%). There was a normal laparoscopic examination in 64 patients (24%).
      There was one false negative laparoscopy that required laparotomy to treat 1
      month later. CONCLUSIONS: Laparoscopy is an accurate modality for the diagnosis
      of both acute and chronic abdominal pain syndromes. These data support the use of
      laparoscopy as the primary invasive intervention in patients with acute and
      chronic abdominal pain.

PMID- 9632859
TI  - Diagnostic laparoscopy in patients with an acute abdomen of uncertain etiology.
AB  - BACKGROUND: There are acute abdominal conditions in which it is difficult to
      establish an indicative diagnosis before laparotomy. A diagnosis is important in
      planning the right abdominal incision or to avoid an unnecessary laparotomy.
      Diagnostic noninvasive procedures such as X-ray studies do not always appear
      conclusive. Diagnostic laparoscopy is the only technique which can visualize the
      abdomen and, by establishing an adequate diagnosis, permits the surgeon to plan
      the right abdominal approach. METHODS: In a prospective study, 65 patients with a
      generalized acute abdomen (no intestinal obstruction or perforation) underwent a
      diagnostic laparoscopy under general anesthesia previous to the planned median
      laparotomy. RESULTS: In 46 patients (70%) diagnostic laparoscopy permitted the
      establishment of an adequate diagnosis, whereas in seven patients (10%) no cause
      for the acute abdomen could be found and an explorative laparotomy was avoided.
      In another 12 patients (20%) insufficient information was obtained during
      laparoscopy and an explorative laparotomy was performed. CONCLUSIONS: A
      conclusive diagnosis was established in 53 patients. This information led to a
      change in the surgical approach in 38 patients (e.g., limited, well-placed
      approach, laparoscopically, or avoidance of an unnecessary laparotomy).
      Diagnostic laparoscopy in this category of patients is a useful technique with
      important therapeutic consequences.

PMID- 9632860
TI  - Laparoscopic evaluation of patients with suspected acute appendicitis.
AB  - BACKGROUND: High error rates are reported in the clinical diagnosis of acute
      appendicitis. This study was undertaken to discover what additional value
      laparoscopy has in the diagnosis of suspected acute appendicitis. METHODS: From
      April 1995 to November 1996, a diagnostic laparoscopy, before open
      appendicectomy, was performed in 100 consecutive patients with suspected acute
      appendicitis. Appendicectomy was performed only if the appendix showed signs of
      inflammation at laparoscopy or if the appendix could not be visualized. RESULTS:
      Twenty-four patients were spared an appendicectomy, and in half of them a new
      diagnosis was established during laparoscopy. The rate of misdiagnosis was 41% in
      female patients of reproductive age and 8% in male patients. There were no cases
      of missed appendicitis in this trial, and all removed appendices showed signs of
      inflammation at histology. CONCLUSIONS: It is safe to rely on the diagnosis made
      at laparoscopy. Its use for establishing diagnosis before appendicectomy in women
      of reproductive age is recommended.

PMID- 9632861
TI  - The role of staging laparoscopy for multimodal therapy of gastrointestinal
      cancer.
AB  - BACKGROUND: This prospective study was conducted to evaluate the accuracy and the
      therapeutic relevance of staging laparoscopy. METHODS: Between June 1993 and
      February 1997 staging laparoscopy was performed in 389 patients with various
      neoplasms. Additionally, 144 selected patients of this group were examined with
      laparoscopic ultrasound using a semiflexible ultrasound probe (7.5 MHz). RESULTS:
      Compared to conventional imaging methods, laparoscopy and laparoscopic ultrasound
      improved the accuracy of staging in 158 of 389 patients (41%). Statistical
      subgroup analysis of 131 patients with gastric cancer showed that the accuracy of
      staging laparoscopy in the detection of distant metastases (68%) was
      significantly higher (p < 0.01) than that of ultrasound (63%) or computed
      tomography (58%). In the whole group, laparoscopy alone disclosed intraabdominal
      tumor dissemination or nonresectable disease in 111 patients. Laparoscopic
      ultrasound displayed additional metastases-i. e., liver metastases (n = 9), M1
      lymph nodes (n = 15), or nonresectable tumors (n = 6) in 30 patients. Although
      metastastic disease was suggested by preoperative imaging, benign lesions were
      found in five patients with laparoscopy and in a further 12 patients with
      ultrasonography. The findings of staging laparoscopy changed the treatment
      strategy in 45% of the patients. Conversion to open surgery was necessary in 5%
      of the cases, and complications related to laparoscopy occured in 4% of the
      patients. CONCLUSIONS: Laparoscopy with laparoscopic ultrasound improves the
      staging of gastrointestinal tumors and has a significant impact on a stage
      adapted surgical therapy.

PMID- 9632862
TI  - Laparoscopic common bile duct exploration by choledochotomy. An effective and
      efficient method of treatment of choledocholithiasis.
AB  - BACKGROUND: Management of cholelithiasis and choledocholithiasis usually requires
      two separate teams-the gastroenterologist/surgical endoscopist and the
      laparoscopic surgical team. This requires two separate procedures that
      potentially increase the overall morbidity and cost. Laparoscopic common bile
      duct exploration by choledochotomy (LCBDE-C) averts this problem with a single
      approach. METHODS: In 1990-1991, unsuspected stones found at laparoscopy with
      intraoperative cholangiogram done routinely underwent postoperative ERCP.
      Residual stones had been found after ERCP in 16 of 22 preoperative ERCP patients
      and we began to seek an alternative technique. Laparoscopic common bile duct
      exploration by choledochotomy has achieved a high rate of success. RESULTS:
      Technically successful LCBDE-C has been accomplished in 143 of 148 patients
      (96.6%). Retained bile duct stones have been found on postoperative cholangiogram
      in three patients (2.0%), all of which have been successfully removed by
      postoperative ERCP. Thus 140 or 148 patients had their bile duct successfully
      cleaned by the one-step technique alone (94.6%). CONCLUSIONS: We believe that
      most laparoscopic surgeons who have acquired the skills of intracorporeal
      suturing can be successful at laparoscopic common bile duct exploration by
      choledochotomy. The disadvantage of T-tube presence will likely be eliminated by
      future developments with intraoperative antegrade sphincterotomy-like procedures,
      but the ability to see both proximal and distal biliary tree with the
      choledochotomy in all cases seems to offer more than adequate results at this
      point in the evolution of the laparoscopic approach to calculus biliary tract
      disease.

PMID- 9632863
TI  - A comparison of laparoscopic ultrasound with digital fluorocholangiography for
      detecting choledocholithiasis during laparoscopic cholecystectomy.
AB  - BACKGROUND: Laparoscopic ultrasound is an alternative to operative cholangiogram
      for evaluation of the common bile duct (CBD) during laparoscopic cholecystectomy.
      It is a safe, fast, and reliable method for detecting choledocholithiasis.
      METHODS: We prospectively evaluated the sensitivity and specificity of
      laparoscopic ultrasound (LUS) and digital fluorocholangiogram (DFCG) in a three
      phase study of 360 consecutive patients. RESULTS: In phase I, 140 patients
      undergoing laparoscopic cholecystectomy had LUS performed first, followed by
      DFCG. Thirteen patients had CBD calculi identified on LUS. Four patients with
      confirmed (two cases) or presumed (two cases) CBD calculi on DFCG were not
      identified on LUS. Thus, the specificity of LUS was 100%, whereas the sensitivity
      was 76.5%. DFCG had four false positives, for a sensitivity of 100% with a
      specificity of 96.7%. LUS was performed, on average, in 6.6 min, whereas DFCG
      required 10.9 min to perform. In phase II, the infusion of saline through a
      cystic duct catheter was performed in instances where the distal CBD could not be
      well seen. This maneuver distended the intrapancreatic portion of the CBD,
      allowing better visualization. Nine stones were identified on LUS in 78 patients,
      increasing the sensitivity to 100%. One false positive DCFG was encountered,
      resulting in a sensitivity of 100% and a specificity of 98.6%. In phase III, we
      performed routine LUS and used DFCG only in select cases. The sensitivity and
      specificity for LUS were 95.7% and 100%, respectively, whereas DFCG had a
      sensitivity of 95.2% and a specificity of 100%. One patient in phase III has
      returned 11 months post-op with a CBD stone. This was initially missed on LUS,
      DFCG, and postoperative ERCP. The sensitivity and specificity in all 360 patients
      were 90% and 100% for LUS and 98.1% and 98.1% for DFCG, respectively. A total of
      five CBD stones were missed by LUS, four early in the study (phase I). One missed
      on LUS in phase III was also missed by DFCG and ERCP. CONCLUSIONS: LUS is a
      reliable alternative to DFCG during laparoscopic cholecystectomy (LC). With
      experience, it is as sensitive as DFCG and more specific. It is more rapidly
      performed than cholangiography.

PMID- 9632864
TI  - Results of the routine use of a modified endoprosthesis to drain the common bile
      duct after laparoscopic choledochotomy.
AB  - BACKGROUND: One hundred eighty-one patients were submitted to laparoscopic common
      bile duct exploration. METHODS: A transcystic approach was used in 147 patients,
      choledochotomy in 14, and both in 20. The indications to perform a choledochotomy
      included stones larger than 20 mm, stones proximal to the cystic duct entrance,
      and cases in which the transcystic duct approach proved impossible or
      unsuccessful. RESULTS: The common bile duct was drained by a T-tube in four
      patients, by laparoscopic sphincterotomy in one, by laparoscopic
      choledochoduodenostomy in one, and by a 10 Fr endoprosthesis in 28. The stent
      placement was technically feasible in all patients but one. The biliary drainage
      was adequate. Mean hospital stay was 2.1 days. Complication was limited to one
      umbilical infection and one self-limited biliary leak. CONCLUSIONS: The procedure
      proved to be technically simple, safe, and efficient, and resulted in a low
      morbidity rate and short hospital stay.

PMID- 9632865
TI  - Tissue thermal damage caused by bipolar forceps can be reduced with a combination
      of plastic and metal.
AB  - BACKGROUND: We created a new 5-mm bipolar forceps. Thermo-insulating plastic was
      used for the creation of the jaws, while the metal conductor is buried deep
      inside the plastic. METHODS: A porcine model was used in experimental testing
      against a standard metallic 5-mm bipolar forceps at three different wattage
      settings (20, 40, 60 W). Histological sections were evaluated by a pathologist
      who was blind to the wattage and instrument tested. RESULTS: The new instrument
      was shown to cause statistically significant reduced thermal damage. In addition,
      its lateral thermal diffusion is superior to standard bipolar forceps.
      CONCLUSIONS: Thermo-insulating plastics can reduce thermal damage to tissue
      during electrosurgery.

PMID- 9632866
TI  - Laparoscopic appendectomy is an acceptable alternative for the treatment of
      perforated appendicitis.
AB  - BACKGROUND: Ever since laparoscopy was first applied to the treatment of
      appendicitis, a controversy has existed as to whether the acknowledged benefits
      of a minimally invasive approach warrant its preference over the conventional
      treatment, which historically has had relatively low morbidity. The purpose of
      this study was to determine if laparoscopic appendectomy should be performed
      preferentially in cases where surgeons are not limited by technical constraints.
      METHODS: A retrospective chart review was performed of 112 patients operated on
      for suspected appendicitis from June 1995 to July 1996. Forty-eight patients
      underwent laparoscopic appendectomy, and 64 had conventional open appendectomy.
      Laparoscopic appendectomy was performed using a three-trocar technique and the
      endoscopic stapler. RESULTS: The histopathological diagnosis of appendicitis was
      confirmed in 82.6% of cases. Overall, laparoscopic appendectomy reduced length of
      hospital stay (1.54 versus 4.09 days; p < 0.0001) compared to conventional open
      appendectomy, with no significant difference in hospital cost ($6430 versus
      $6669; p = ns). Although the total OR time was longer in the laparoscopic group
      (75.8 versus 60.2 min; p < 0.0001), laparoscopy resulted in both a reduction in
      length of stay (2.17 versus 6.27 days; p < 0.0001) and hospital cost ($7506
      versus $10,504; p < 0.02) for cases of perforated appendicitis. Conversion to
      open appendectomy was performed in 6% of patients, all of whom had perforated
      appendicitis. CONCLUSIONS: Our data suggest that most cases of acute appendicitis
      with suspected perforation could be managed laparoscopically. Laparoscopic
      appendectomy significantly reduces length of stay and hospital costs in patients
      with perforated appendicitis.

PMID- 9632867
TI  - Laparoscopic splenectomy in beta-thalassemia major patients. Advantages and
      disadvantages.
AB  - BACKGROUND: Splenectomy is indicated in patients with thalassemia major when they
      develop hypersplenism with subsequent need for increased transfusions. Extreme
      splenomegaly is considered a restrictive factor for laparoscopic splenectomy in
      these patients. METHODS: Laparoscopic splenectomy was undertaken in 12 beta
      thalassemia major patients with massive splenomegaly. The devascularization of
      the organ was performed with serial ligations of the splenic vessels starting
      from the lower pole of the organ. The spleen was extracted from the abdominal
      cavity through a 5-cm incision in the left iliac fossa, which incorporated two
      port sites. RESULTS: The procedure was concluded laparoscopically in 10 cases,
      while two patients were converted due to difficulty in controlling bleeding from
      branches of the splenic vein. The patients tolerated the procedure well and had a
      postoperative hospital stay of 3-6 days. CONCLUSIONS: From our limited initial
      experience it seems that laparoscopic splenectomy in the difficult setting of
      thalassemia major patients is feasible, but extreme care is required in order to
      avoid hemorrhagic complications.

PMID- 9632868
TI  - Comparative study of two-dimensional and three-dimensional vision systems for
      minimally invasive surgery.
AB  - BACKGROUND: The aim of this comparative study was to gain subjective and
      objective data to determine for which operative tasks three-dimensional (3-D)
      vision systems are superior to two-dimensional (2-D) systems and to demonstrate
      any advantages or disadvantages of 3-D systems. METHODS: A model with five
      standardized tasks including sewing and knotting was developed to objectively
      measure performance times and to count technical faults. In our training center
      for minimally invasive surgery, surgeons involved in basic and advanced
      laparoscopic courses trained using both 2-D and 3-D vision systems. They
      subsequently completed analog scale questionnaires to record a subjective
      impression of comparative ease of operation tasks under 2-D and 3-D vision and to
      identify perceived deficiencies in the 3-D system. RESULTS: Compared to 2-D
      vision, the objective performance time was significantly shorter and
      significantly less mistakes were made using 3-D vision. All operative tasks were
      subjectively judged significantly easier under 3-D vision. CONCLUSIONS: Users
      with a normal capability for spatial perception can perform standard tasks more
      quickly and safely using 3-D vision, and a greater benefit is apparent for more
      complicated surgical maneuvers.

PMID- 9632869
TI  - Prospective, multicenter study of laparoscopic ventral hernioplasty. Preliminary
      results.
AB  - BACKGROUND: A standard technique for laparoscopic ventral hernioplasty
      (peritoneal onlay using an expanded polytetrafluoroethylene [ePTFE] patch for
      hernias >/=4 cm2) is being used in a prospective, multicenter, long-term study.
      METHODS: Demographic, operative, and postoperative data were collected and
      analyzed. Follow-up clinical evaluations were conducted 7-10 days, 4 weeks, 6
      months, 1 year, and then annually after surgery in all patients. RESULTS: In the
      first 2 years of the study, 144 patients were enrolled; nine were lost to follow
      up. The mean operating time was 120 min. The mean follow-up was 222 days (range 5
      731). Postoperative complications were five infections, three cases of prolonged
      ileus, one bowel obstruction, 23 seromas (15 resolved without intervention), and
      six hernia recurrences. Hospital discharge occurred a mean of 2.3 days after
      surgery and return to normal activity a mean of 15 days postoperatively.
      CONCLUSIONS: Laparoscopic prosthetic ventral hernioplasty avoids the large wound
      required in open repairs, with attendant complications and recurrences, and
      appears safe, especially if an ePTFE mesh is used. Compared with conventional
      open ventral hernioplasty, the laparoscopic technique may also allow shorter
      hospitalization and a quicker return to normal activities after surgery.

PMID- 9632870
TI  - Major vascular injuries during laparoscopic cholecystectomy. An institutional
      review of experience with 2589 procedures and literature review.
AB  - BACKGROUND: Since the introduction of laparoscopic cholecystectomy, major
      vascular injury has been a rare but very serious complication of the procedure.
      METHODS: All 2,589 laparoscopic cholecystectomies performed at our institution
      between May 1, 1990, and December 31, 1996, were retrospectively reviewed to
      identify major vascular injury and the mechanisms involved. All these procedures
      were performed either by surgical attendings or senior surgical residents.
      RESULTS: During the 1,372 operations performed here between May 1, 1990, and May
      1, 1994, there were three major vascular injuries. One was to a portal vein, due
      to dissection during lysis of adhesions; the other two, to the aorta and vena
      cava, were due to trocar insertions. There was one mortality secondary to liver
      failure following repair of the portal vein injury. Between May 1, 1994, and
      December 1, 1996, there were no major vascular injuries; our overall incidence
      was 0.11%. A review of the literature on this subject is included. CONCLUSIONS:
      Laparoscopic cholecystectomy is a very safe procedure; major vascular injury is a
      rare complication, but mandates early recognition and consideration of prompt
      exploratory laparotomy. These injuries can be avoided by strict adherence to
      laparoscopic guidelines: obtaining pneumoperitoneum by the open technique,
      inserting side trocars under direct vision, elevating the abdominal wall prior to
      trocar insertion, and training surgeons in a laparoscopic laboratory.

PMID- 9632871
TI  - Prospective randomized study of stress and immune response after laparoscopic vs
      conventional colonic resection.
AB  - METHODS: In order to evaluate the stress and immunological response to
      laparoscopic and conventional colon resection we operated on male Wistar rats
      (350-380 g), performing either laparoscopic (n = 15) or open colon resection (n =
      15). A third group (n = 10) underwent anesthesia only. Immediately before and
      after surgery as well as 1 and 7 days postoperatively a 1 ml sample of blood was
      taken from the retrobulbar veinous plexus. Stress (corticosterone) and immune
      parameters (neopterin and interleukin [IL] 1-beta) were measured. Furthermore,
      the body weight as a parameter of postoperative recovery was monitored. RESULTS:
      The analysis of variance showed significant differences between the three groups
      over a period of 1 week (p < 0.0001 for corticosterone, p = 0.0854 for IL 1-beta,
      p = 0. 0045 for neopterin). Additionally in a t-test significant differences were
      found between the laparoscopic and conventional group with regard to
      corticosterone (p = 0.08), to neopterin (p = 0. 045), and to IL 1-beta (p =
      0.0043) at the end of the operation. One week after the operation the stress and
      immune parameters were back to normal levels in each group except IL 1-beta, but
      the recovery indicated by body weight was different according to the kind of the
      applied operative procedure: 7 days postoperatively the rats lost 5. 99% of their
      body weight after open surgery and only 2.4% after laparoscopic surgery. After
      anesthesia only the body weight increased by about 4.8%. CONCLUSION: Laparoscopic
      colon resection alters the stress and immune system of healthy rats less than
      open colon resection. This observation is confirmed by the quicker recovery in
      laparoscopically operated rats.

PMID- 9632872
TI  - Alterations in hepatic function during laparoscopic surgery. An experimental
      clinical study.
AB  - BACKGROUND: Very few studies have been done on the consequences of
      pneumoperitoneum on hepatic function. At present, there is no consensus on the
      physiopathological hepatic implications of pneumoperitoneum. The purpose of this
      clinical study was to evaluate the effects of pneumoperitoneum on hepatic
      function in 52 patients treated with laparoscopic procedures. METHODS: Thirty-two
      laparoscopic cholecystectomies and 20 nonhepatobiliary laparoscopic procedures
      were performed in 52 patients (12 men and 40 women) with a mean age of 44 years
      (range, 15-74). All patients had normal values on preoperative liver function
      tests. The anesthesiologic protocol was uniform, with drugs at low hepatic
      metabolism. The 32 cholecystectomies were randomized into 22 performed with
      pneumoperitoneum at 14 mmHg and 10 performed at 10 mmHg. All nonhepatobiliary
      laparoscopic procedures were performed with a pneumoperitoneum of 14 mmHg. The
      postoperative serologic levels of AST, ALT, bilirubin, and prothrombin time were
      measured at 6, 24, 48, and 72 h. The serologic changes were related to the
      procedure, the duration, and the level of pneumoperitoneum. RESULTS: Mortality
      and morbidity were nil. All 52 patients had a postoperative increase in AST, ALT,
      bilirubin, and lengthening in prothrombin time. Slow return to normality occurred
      48 or 72 h after operation. The increase of AST and ALT was statistically
      significant and correlated both to the level (10 versus 14 mmHg) and the duration
      of pneumoperitoneum. CONCLUSIONS: The duration and level of intraabdominal
      pressure are responsible for changes of hepatic function during laparoscopic
      procedures. Although no symptom appears in patients with normal hepatic function,
      patients with severe hepatic failure should probably not be subjected to
      prolonged laparoscopic procedures.

PMID- 9632873
TI  - Coagulation modifications after laparoscopic and open cholecystectomy in a swine
      model.
AB  - BACKGROUND: The stress response to surgical trauma precipitates a state of
      transient hypercoagulation. Studies have demonstrated that laparoscopic surgery
      results in a diminished stress response compared to open surgery. The aim of this
      study was to determine the extent of postoperative hypercoagulability following
      laparoscopic cholecystectomy (LC) compared to open cholecystectomy (OC). METHODS:
      Twenty-one pigs were randomly selected to undergo LC (N = 10) or OC (N = 11).
      Whole blood was collected preoperatively and on postoperative days (PODs) 1, 2,
      and 3 for determination of viscoelastic changes using a thromboelastography (TEG)
      coagulation analyzer. Four parameters were calculated from the TEG: R (reaction
      time), K (coagulation time), alpha (rate of clot formation), and MA (maximal
      amplitude). Antithrombin III (AT III) level was measured preoperatively and on
      POD 1. RESULTS: After OC, three of four TEG parameters changed to reflect a state
      of hypercoagulation. Only MA values were significantly changed after LC.
      Comparison between OC and LC showed no difference in the TEG parameter. There was
      no significant change in AT III levels after LC or OC. CONCLUSIONS: OC results in
      postoperative hypercoagulation typically encountered in open abdominal surgery.
      Although there were no differences in TEG or AT III between the two groups, after
      the laparoscopic approach all but one TEG parameter remained unchanged,
      suggesting a diminished hypercoagulable state. By reducing postoperative
      hypercoagulation, laparoscopic surgery may reduce the risk of developing
      postoperative venous thrombosis.

PMID- 9632874
TI  - A randomized, controlled, clinical study of laparoscopic vs open tension-free
      inguinal hernia repair.
AB  - BACKGROUND: The aim of this prospective, randomized, controlled clinical study
      was to compare laparoscopic transabdominal preperitoneal (TAPP) hernia repair
      with a standard tension-free open mesh repair (open). METHODS: A total of 108 low
      risk patients with unilateral (primary or recurrent) or bilateral hernias were
      randomized to TAPP (group 1 = 52 cases) or open (group 2 = 56 cases). The outcome
      measures included operating time, complications, postoperative pain, return to
      normal activity, operating theater costs, and recurrences. RESULTS: The mean
      operative time was longer for the TAPP than for the open group only in unilateral
      primary hernias. At rest, the median Visual Analog Scale (VAS) score was higher
      for group 1 than group 2 at 48 h postoperatively. Mild to discomforting pain in
      the inguinal region after 7 days, night pain after 30 days, and inguinal
      hardening after 3 months were more frequent in group 2 than group 1. No
      significant differences were observed in return to normal activities between the
      groups. One hernia recurrence was observed after 1 month in group 1. TAPP was
      significantly more expensive than open. CONCLUSIONS: TAPP was associated with
      less postoperative pain than open. The increase in operating theater costs,
      however, was dramatic and was not compensated by shorter time away from work.
      TAPP should not be adopted routinely unless its costs can be drastically reduced.

PMID- 9632875
TI  - Eosinophilic enteritis. A case for diagnostic laparoscopy.
AB  - Eosinophilic enteritis is rare. This report of a single case involving the distal
      ileum demonstrates the importance of laparoscopy in the diagnosis of this
      disease. An adequate biopsied segment of intestine can be obtained using complete
      intracorporeal techniques and three portals. Histiopathologic confirmation will
      insure proper treatment. The effectiveness of laparoscopy as a diagnostic tool
      cannot be understated. Surgeons should continue to encourage its use in similar
      patients with ill-defined abdominal pain, nonspecific laboratory results, and
      radiographic findings that are inconclusive and do not allow one to initiate
      appropriate therapy.

PMID- 9632876
TI  - Subfascial hemorrhage after endoscopic perforator vein ligation. Control with
      balloon tamponade.
AB  - Ligation of perforator veins in the lower extremity for the treatment of venous
      ulceration can be performed using a minimally invasive technique with endoscopic
      instruments. Several studies have documented that the endoscopic technique has a
      lower wound-related complication rate compared to open perforator vein ligation.
      We report the complication of postoperative subfascial hemorrhage requiring
      reexploration after subfascial endoscopic perforator vein ligation and describe a
      minimally invasive method for its control using balloon tamponade.

PMID- 9632877
TI  - An unusual case of endometrial trocar site implantation.
AB  - We present the case of a 35-year-old woman with a history of apparent bilateral
      hernia who had a surgical intervention that included a diagnostic laparoscopy
      converted to open laparotomy. The patient experienced endometrial implants
      exclusively at trocar sites. This case is cited as validation of the
      pneumoperitoneum-induced free cell implantation theory, or the so-called
      aerosolization theory.

PMID- 9632878
TI  - Laparoscopic-assisted small bowel resection for a bleeding leiomyoma.

PMID- 9632879
TI  - Computer-controlled endoscopic performance assessment system.
AB  - We have devised an advanced computer-controlled system (ADEPT) for the objective
      evaluation of endoscopic task performance. The system's hardware consists of a
      dual gimbal mechanism that accepts a variety of 5.0-mm standard endoscopic
      instruments for manipulation in a precisely mapped and enclosed work space. The
      target object consists of a sprung base plate incorporating various tasks. It is
      covered by a sprung perforated transparent top plate that has to be moved and
      held in the correct position by the operator to gain access to the various tasks.
      Standard video endoscope equipment provides the visual interface between the
      operator and the target-instrument field. Different target modules can be used,
      and the level of task difficulty can be adjusted by varying the manipulation,
      elevation, and azimuth angles. The system's software is designed to (a) prompt
      the surgeon with the information necessary to perform the task, (b) collect and
      collate data on performance during execution of specified tasks, and (c) save the
      data for future analysis. The system was alpha and beta tested to ensure that all
      functions operated correctly.

PMID- 9632880
TI  - The Hunt-Reich trocar. A versatile instrument.

PMID- 9632882
TI  - News and notices 

PMID- 9632881
TI  - A simple technique for delivery of bulky gallbladders during laparoscopic
      cholecystectomy.

PMID- 9632883
TI  - RNA recognition and regulation of HIV-1 gene expression by viral factor Tat.
AB  - Viral transcription factor Tat is a small nuclear protein containing a large
      number of basic amino acids. The tat gene consists of two exons but only the
      first encoding 72-amino acid polypeptide is necessary for protein activity. Since
      the second exon is poorly conservative the total number of amino acids among Tat
      proteins from different strains of HIV-1 varies from 86 to 130. Tat protein acts
      as trans-activator of HIV genome transcription. It is absolutely required for
      viral functioning. Tat increases processivity of RNA-polymerase II by abolition
      of transcription blockade, which appears after polycondensation of the first 60
      70 nucleotides of either HIV mRNA, i.e., it acts as antiterminator. For
      manifestation of its activity Tat specifically binds to the double stranded RNA
      fragment called TAR which is located at the 5'-terminus of all HIV mRNAs. The TAR
      structure contains a hairpin and a side loop. The Tat-binding region includes
      only a site of the loop; manifestation of Tat activity in vivo requires the full
      TAR and additional cellular co-factors.

PMID- 9632884
TI  - D-Glyceraldehyde-3-phosphate dehydrogenase: structural basis and functional role
      of the acyl transfer reactions.
AB  - The catalytic mechanism of D-glyceraldehyde-3-phosphate dehydrogenase is
      considered in the light of the available structural information. The design
      features of the enzyme molecule determining the pathway of the acyl transfer,
      i.e., the transfer of the acyl group produced in the oxidative step of the
      reaction to one of the two acceptors, inorganic phosphate or water, are
      discussed. The properties of enzyme forms possessing cysteine residues oxidized
      to sulfenic acid derivatives are described. The participation of these residues
      in the acyl transfer to water is considered.

PMID- 9632885
TI  - Formation of lactose-resistant aggregates of human platelets induced by the
      mistletoe lectin and differential signaling responses to cell contact formation
      by the lectin or thrombin.
AB  - Human platelets afford a suitable and physiologically relevant model to study
      receptor-dependent cell aggregation and ensuing biosignaling reactions. Since
      cell surface glycoconjugates can serve as ligands in recognitive protein-
      carbohydrate interactions, it is of interest to investigate the reactivity of
      such epitopes for a plant lectin and the elicited intracellular responses.
      Therefore, the galactose-specific lectin (Viscum album agglutinin, VAA) was
      employed as a tool for this purpose. It was found that VAA induced platelet
      aggregation at a concentration of 2.5 microgram/ml using 2.5. 108 cells/ml,
      composed of the formation of both lactose-sensitive (Lac+) and lactose-resistant
      (Lac-) intercellular contacts. Lac- aggregates were formed only by metabolically
      active platelets of about 70% of the samples from the group of studied
      volunteers. The requirement of metabolic activity for formation of these contacts
      which no longer depend on lectin--ligand recognition was underscored by the lack
      of their appearance in the presence of metabolic inhibitors such as
      nordihydroguaiaretic acid, trifluoperazine, N-ethylmaleimide and menadione. With
      respect to biosignaling, the effective aggregation of platelets did not affect
      the basal level of Ca2+ in cells and reduced the rate of the menadione-dependent
      generation of H2O2. In parallel series platelet aggregation induced by bovine
      thrombin (0.03 U/ml) triggered an increase in the cytoplasmic Ca2+ level and an
      enhancement of the H2O2 generation. Overall, these results imply metabolically
      controlled post-binding reactions which strengthen the lectin-induced cell
      association and demonstrate differential responses with respect to the Ca2+ level
      and H2O2-generation between lectin- or thrombin-mediated aggregation of human
      platelets.

PMID- 9632886
TI  - Photoprotector and antioxidant properties of histamine-containing peptidomimetics
      in the photooxidation of glycyltryptophan.
AB  - The natural imidazole-containing dipeptide carnosine in vitro exhibits several
      antioxidant properties; however, in vivo its activity is limited due to enzymatic
      hydrolysis. A family of original histamine-containing peptidomimetics, i.e.,
      carcinine (beta-alanylhistamine), N-acetylcarcinine (N-acetyl-beta
      alanylhistamine), and L-prolylhistamine, which exhibit significant resistance to
      dipeptidases and retain antioxidant activity, was synthesized. The effect of
      these compounds on chemiluminescence of glycyltryptophan (Gly-Trp) associated
      with its photooxidation at the wavelengths over 280 nm and oxidation
      photosensitized by riboflavin and Rose Bengal was studied. It is shown that all
      three peptidomimetics efficiently react with singlet oxygen with the rate
      constant 9.107 M-1.sec-1, exhibit free-radical scavenging activity in the course
      of riboflavin-sensitized Gly-Trp oxidation (C50% = 8-15 mM), and quench the
      photoexcited triplet states of the molecules. Unlike these peptidomimetics,
      carnosine does not react with superoxide generated during the photooxidation of
      Gly-Trp in the used test system. The data demonstrate photoprotector and
      antioxidant properties of histamine-containing peptidomimetics in the
      photooxidation of biological molecules.

PMID- 9632887
TI  - Effect of light on generation of colored silver colloids in protein solutions.
AB  - The exposure to light (20 mW/cm2, an incandescence lamp) of weakly alkaline
      protein solutions which contained silver nitrate and formaldehyde initiated
      reduction of silver ions with the subsequent generation of colored silver
      colloids. At light intensities lower than 0.2 mW/cm2 the generation of colored
      silver colloids was delayed. The rate of silver reduction depended on the protein
      type and on the light spectral structure. In particular, solutions which
      contained prealbumin, lysozyme, gamma-globulin, and transferrin were more
      photosensitive than solutions which contained albumin, pepsin, and beta-amylase.
      The formation of [Ag(NH3)2]+ complex after an addition of ammonium ions into the
      solutions preferentially suppressed silver reduction in the dark and under
      exposure to red light, thus resulting in a significant difference in the time of
      appearance of colored silver colloids when the solutions were exposed to violet
      or red light. These findings are promising for the elaboration of selective
      silver development of proteins in polyacrylamide gels.

PMID- 9632888
TI  - Dynamics of association-dissociation of the c-myc gene with the nuclear matrix
      during activation-inactivation of the gene.
AB  - The dynamics of association-dissociation of the c-myc protooncogene-containing
      chromatin with the nuclear matrix (NM) were studied in rat liver cells during
      transient activation of the gene. The gene was activated by injection of
      cycloheximide (CHI) to animals. Two periods of the c-myc gene activation were
      found by RNA--DNA hybridization blotting during the first 12 h after the
      injection of CHI with the maxima at 3-4 and 9-10 h. The NM-associated chromatin
      was also found by DNA--DNA hybridization blotting to have two periods of an
      increase in the amount of the c-myc gene. The c-myc gene activation-inactivation
      dynamics during the first period were conjugated with the dynamics of its
      association-dissociation with the NM. During the second period the c-myc gene
      amount in the NM-associated chromatin was the same as during the first period but
      the transcriptional activity of the c-myc gene during the second period was
      significantly lower. The results suggest two activation stages of the gene(s): 1)
      the production of a topologically independent chromatin loop by the association
      to the NM; 2) the initiation of the gene transcription in the produced loop. Both
      stages seem to take place during the first period of the c-myc gene activation
      while during the second period only the first stage occurred and the second stage
      was only partially realized.

PMID- 9632889
TI  - Thermophilic strain Bacillus species AA contains several site-specific
      endonucleases.
AB  - Thermophilic strain Bacillus species AA contains several site-specific
      endonucleases and three of them have been identified. BspAAI recognizes the
      sequence 5'-C downward arrow TCGAG-3' and cleaves it after the first "C" forming
      4-nucleotide 5'-ends and is an isoschizomer of XhoI. BspAAII recognizes the
      sequence 5'-T downward arrow CTAGA-3' and cleaves it after the first "T" forming
      4-nucleotide 5'-ends and is an isoschizomer of XbaI. BspAAIII recognizes the
      sequence 5'-GGATCC-3' and is an isomer of BamHI. The optimal temperature and pH
      values are 42-48 degreesC and 7.0-8.0, respectively.

PMID- 9632890
TI  - Modification of the functional activity of neutrophils treated with acute phase
      response proteins.
AB  - The effects of alpha1-acidic glycoprotein (AGP) and its subfractions (glycoforms)
      with different affinity for concanavalin A on generation of H2O2 by human
      neutrophils exposed to stimulators of different nature, namely, galactose
      specific mistletoe (Viscum album) lectin (VAA), digitonin, and N-formyl-Met-Leu
      Phe, a chemotactic peptide (FMLP), were studied. Within the concentration range
      of 13-500 microgram/ml, AGP and its glycoforms produced dose-dependent inhibition
      of digitonin-induced cell responses. AGP also inhibited the VAA-induced
      generation of H2O2; however, this cell response was potentiated by low
      concentrations (50 microgram/ml) of AGP and AGP-A. FMLP induced the most
      consistent response of neutrophils, which changed only slightly in the presence
      of AGP and AGP-B; however, low concentrations of AGP-A inhibited this response.
      The presence of sialic acid in the terminal position of carbohydrate antennae of
      AGP is not necessary for its inhibitory effect on human neutrophil respiratory
      burst because asialo-AGP (250 microgram/ml) inhibited H2O2 generation by cells
      stimulated with agonists of the NADPH-oxidase system of phagocytes. In contrast
      to AGP, two other acute phase response proteins displaying a lectin activity (C
      reactive protein and serum amyloid P component) within the concentration range of
      10-100 microgram/ml produced no significant effect on H2O2 generation by
      stimulated neutrophils. These data suggest that AGP is an effector molecule
      responsible for feedback regulation of the functional activity of neutrophils.

PMID- 9632891
TI  - Specificity of humoral and cellular immune response against recombinant particles
      of nucleocapsid protein of human hepatitis B virus in rabbits.
AB  - Nucleocapsid (core) protein of hepatitis B virus (HBcAg) induces potent cellular
      and humoral responses that have a clear protective potential. Rabbits were
      immunized by particles formed by recombinant molecules of HBcAg carrying N
      terminally inserted heterologous sequences. Specificity of humoral and cellular
      immune response against HBcAg and selection of HBcAg epitopes was surveyed.
      Immunological properties of the recombinant particles were similar to those of
      the original HBcAg. Recombinant particles were not toxic to the peripheral blood
      mononuclear cells (PBMC) of non-immune or HBcAg-immunized animals ex vivo.
      Proliferative response of PBMC (T-lymphocytes) to HBcAg in immunized animals
      increased in a concentration-dependent manner in the broad interval of HBcAg
      concentrations (10-104 ng/ml). On the contrary, a narrow bell-shaped HBcAg dose
      dependence curve was earlier observed for T-lymphocytes of donors immune to HBV
      after natural infection that was probably due to the cytotoxic effect of HBcAg on
      the expressing cells. Specificity of humoral and cellular immune response against
      HBcAg particles in the immunized animals and in natural infection with hepatitis
      B virus (HBV) was compared. Immunization with recombinant HBcAg particles induced
      potent anti-HBcAg antibody responses: high (up to 2.107) titers of anti-HBcAg
      antibodies were reached. Appearance of anti-HBcAg antibodies was in every case
      preceded by an increasing T-cell response to the whole protein and HBcAg-derived
      peptides, thus mimicking immune responses during acute HBV infection in humans. A
      predominant universal (haplotype-independent) T-helper cell epitope (amino acid
      residues (aa) 61-85 of HBcAg (p61-85)) was recognized by T-cells of all animals.
      Transient antibody response against p61-85 was recorded during the early stages
      of immunization in spite of the fact that a major B-cell epitope localized in
      this region is supposed to be purely conformational. A sequence representing
      another cluster of immunodominant T-cell epitopes of mice and HBV infected
      humans, aa 121-140 (p121-140), was not immunogenic on the T-cell level. However,
      it appeared to be a potent B-cell immunogen, despite a common assumption that
      HBcAg and p121-140 are not cross-reactive at the B-cell level. A possibility that
      anti-p121-140 antibodies were induced by an exposed region of the native
      particulate HBcAg and not by the denatured protein molecules, was confirmed by
      recognition of the particulate HBcAg by antibodies specific to synthetic peptides
      representing aa 120-140 of HBcAg. The data point to the exposition of aa 121-140
      on the surface of the particles.

PMID- 9632892
TI  - Steady-state kinetics of peroxidation of 2-chloro-10-(3-dimethylaminopropyl)
      phenothiazine catalyzed by horseradish peroxidase 
AB  - The steady-state kinetics of peroxidation of 2-chloro-10-(3-dimethylaminopropyl)
      phenothiazine (Aminazine) catalyzed by horseradish peroxidase was studied.
      Aminazine was shown to be a substrate of peroxidase which is oxidized with a slow
      rate. The values of the catalytic constant (kcat) and Km were measured within the
      pH range from 4.5 to 7.0. In the presence of Aminazine, there was an increase in
      the rate of peroxidation of potassium ferrocyanide. Binding of an activator to
      the peroxidase active center caused an increase in the enzyme affinity for
      ferrocyanide, although had no effect on the kcat value within the pH range from 5
      to 7.

PMID- 9632893
TI  - Role of hydrophobic interactions in protein chain folding during biosynthesis.
AB  - It has been found that hydrophobic potentials of 30- to 40-amino acid fragments
      of amino acid sequences of myoglobin, cytochrome b5, alpha-chymotrypsin, and
      seven other globular proteins analyzed are similar and correspond to free
      energies of formation of limited hydrophobic nuclei.

PMID- 9632894
TI  - Discrimination between conformational states of mitochondrial cytochrome P-450scc
      by selective modification with pyridoxal 5-phosphate.
AB  - Electrophoretically homogeneous cytochrome P-450scc preparation isolated by the
      standard method from adrenal cortex mitochondria comprises two protein forms
      differing in the accessibility of their amino groups to specific chemical
      modification with pyridoxal 5-phosphate. The protein form whose lysine amino
      groups are accessible to the modifier constitutes about 60-70% of the
      preparation. Being covalently bound to pyridoxal 5-phosphate, this protein form
      loses enzymatic activity and affinity for adrenodoxin. This protein form can be
      separated by affinity chromatography on adrenodoxin-Sepharose. The cytochrome P
      450scc form whose amino groups are not accessible to the modifier is retained on
      the affinity matrix, and after elution from adrenodoxin-Sepharose has the
      absorption spectrum typical of the high-spin protein with a spectral homogeneity
      index A392/A278 = 1.0. The enzymatic activity of the hemoprotein form whose
      lysine amino groups are inaccessible to the modification is identical to that of
      the initial unmodified protein.

PMID- 9632895
TI  - Involvement of aspartate/glutamate antiporter in uncoupling effect of fatty acids
      in heart mitochondria.
AB  - Earlier it was shown that fatty acid-induced uncoupling in liver mitochondria is
      suppressed by the substrates of the aspartate/glutamate antiporter (V. N.
      Samartsev, A. V. Smirnov, I. P. Zeldi, O. V. Markova, E. N. Mokhova, and V. P.
      Skulachev (1997) Biochim. Biophys. Acta, 1319, 251-257). In this study it is
      shown that in heart mitochondria aspartate, glutamate, and diethyl pyrocarbonate
      do not affect oxygen consumption and membrane potential in the presence of
      laurate at pH 7.4. These compounds have a weak (versus carboxyatractylate)
      coupling effect at pH 7.0. This effect is manifested only in the presence of
      carboxyatractylate, magnesium, and phosphate in the incubation medium. It is
      suggested that these tissue-specific effects are due not only to the specific
      characteristics of aspartate/glutamate antiporter, but also to the differences in
      the content of endogenous metabolites in heart mitochondria.

PMID- 9632896
TI  - Bioluminescence of free and poly(vinyl alcohol) cryogel-entrapped recombinant
      Escherichia coli cells expressing firefly luciferase.
AB  - Bioluminescence of free and poly(vinyl alcohol) cryogel-entrapped recombinant E.
      coli cells expressing firefly luciferase was investigated. It was shown that
      bioluminescence intensity and time-course of the bioluminescent signal changed
      upon immobilization and depended on intracellular ATP concentration and
      permeability of the cell membrane.

PMID- 9632897
TI  - Stress protein of cyanobacteria CP36: interaction with photoactive complexes and
      formation of supramolecular structures 
AB  - Cyanobacterium Anacystis nidulans R2, Synechocystis sp. PCC 6803 (wild-type
      strain and mutants Delta2 and Delta3 lacking PSII and PSI, respectively), and
      Synechocystis sp. BO 9201 synthesize the pigment--protein complex CP36 (CPIV-4,
      CP43') under iron deficiency in the medium. Accumulation of CP36 is accompanied
      by structural reorganizations in the photosynthetic membranes. Integrating mean
      times of excitation relaxation (quenching) are 2.2 nsec (CP36), 1 nsec (PSI), and
      420 psec (PSII in Fm state). The energy migration between CP36 and the
      photosystems can be described by a model of a one-layer ring of CP36 around core
      complexes. The excitation from CP36 to PSI is transferred within <10 psec. The
      energy transfer from CP36 to PSII occurs during 170 psec. Cells with low content
      of CP36 probably contain only a latent fraction of unbound to phycobilisomes PSII
      which is the analog of PSIIbeta of higher plants. In PSI there are four binding
      sites for CP36 monomers per RC. PSII can bind up to 32 molecules of CP36 per RC.
      Cells with a large amount of CP36 contain monomer form of PSII core-complex which
      can bind eight tetramers of CP36 (8 binding sites). In conditions of iron
      deficiency only one monomer of a dimer PSII core-complex is destroyed and
      released chlorophyll is accumulated in CP36. Accumulation of CP36 in A. nidulans
      cells can be accompanied by membrane stacking which is similar to the stacking in
      chlorophyll b-containing organisms. The stacking can occur in the region of
      localization of PSII latent fraction bound to CP36. The membrane stacking shields
      PSII stromal surfaces from the aqueous phase for activation of electron transfer
      on the acceptor side of PSII.

PMID- 9632898
TI  - Changes in E. coli inorganic pyrophosphatase structure induced by binding of
      metal activators.
AB  - The three-dimensional structures of E. coli inorganic pyrophosphatase (PPase) and
      its complexes with Mn2+ in a high affinity site and with Mg2+ in high and low
      affinity sites determined by authors in 1994-1996 at 1.9-2.2 A resolution are
      compared. Metal ion binding initiates the shifts of alpha-carbon atoms and of
      functional groups and rearrangement of non-covalent interaction system of
      hexameric enzyme molecule. As a result, the apoPPase with six equal subunits
      turns after Mg2+ binding into the structure with three types of subunits
      distinguished by structure and occupance of the low affinity Mg2+ site. Induced
      asymmetry reflects the subunit interactions and cooperativity between Mg2+
      binding sites. These molecular rearrangements are structural basis to account for
      special features of the enzyme behavior and to propose one of the pathways for
      enzymatic activity regulation of constitutive PPases in vivo.

PMID- 9632899
TI  - Effect of pH on tobacco anionic peroxidase stability and its interaction with
      hydrogen peroxide.
AB  - The effect of extremely acidic pH on the stability of tobacco peroxidase and
      lignin peroxidase holoenzymes has been studied. Stabilization of tobacco
      peroxidase holoenzyme in the presence of calcium cations at pH < 2 and
      stabilization of lignin peroxidase at pH > 2 in the presence of veratryl alcohol
      have been shown. The dependence of the reaction rate constant for hydrogen
      peroxide interaction with tobacco peroxidase on pH suggests that the reaction
      rate is under control of a group with pK of 2.5. A tobacco peroxidase model
      structure has been created by means of homology modeling on the basis of the
      tobacco peroxidase sequence and the coordinates of peanut peroxidase crystal
      structure. The model structure demonstrates the presence of the negatively
      charged Glu-141 at the entrance to the active site and its electrostatic
      repulsion from heme propionates and triad of Asp-76, -79, and -80 residues. The
      results on tobacco holoperoxidase stabilization at pH 1.8 in the presence of
      calcium cations and drop in reaction rate constant for the enzyme interaction
      with hydrogen peroxide are explained by a hypothetical formation of ionic bonds
      between Glu-141 and the triad of aspartic acid residues via calcium cation
      lowering the accessibility of the active site and stabilizing the holoenzyme.

PMID- 9632900
TI  - Anticholinergic versus beta 2-agonist on gas exchange in COPD: a comparative
      study in 15 patients.
AB  - beta-agonist bronchodilators are known to influence gas exchange and ventilation
      perfusion relationships in asthmatic patients, where they induce hypoxaemia via
      hypoxic vasoconstriction. As this effect could have serious consequences in
      chronic obstructive pulmonary disease (COPD) patients with chronic hypoxaemia,
      alternative agents have been sought. It has been shown that inhaled
      anticholinergic drugs may be of value in this condition. In the present study, we
      compared the effects of salbutamol (Sb) and ipratropium bromide (IB) inhalation
      on gas exchange in 15 patients with stable COPD. All patients had a history of
      COPD (mean arterial oxygen tension (Pa,O2) = 8.2 +/- 1.0 kPa (61.8 +/- 7.3 mmHg)
      forced expiratory volume in one second (FEV1) = 39 +/- 12%; FEV1/vital capacity
      (VC) = 42 +/- 6%) and no evidence of acute respiratory failure. Haemodynamic and
      gas exchange data were recorded after right catheterization by the multiple inert
      gas elimination technique. Measurements were made under basal conditions, after
      two puffs of freon propellant (placebo) and after two puffs of either 200
      micrograms Sb or 200 micrograms IB in a randomized design. Sb and IB reduced
      airway resistances to the same extent, but had no significant influence on the
      haemodynamic and ventilation parameters. There was a slight but significant
      decrease in arterial carbon dioxide tension (Pa,CO2) = 6.0 +/- 0.8 versus 6.4 +/-
      0.8 kPa (45.4 +/- 5.9 versus 47.9 +/- 6.3 mmHg) p < 0.05 with an enhanced
      perfusion distribution heterogeneity and a slight improvement in ventilation
      homogeneity shown by a decrease of the decimal logarithm of SD of the ventilation
      distribution (LogSDV) after inhalation of IB relative to control. Since these
      alterations did not affect arterial oxygen tension we concluded that inhalation
      of these doses of salbutamol or ipratropium bromide do not affect gas exchange in
      patients with stable chronic obstructive pulmonary disease. The normal home
      treatment: inhalation of two puffs of these bronchodilating drugs thus appears to
      be safe. The choice of agent will depend on the extent of the bronchodilator
      effect in a given individual.

PMID- 9632901
TI  - The efficacy of noninvasive mechanical ventilation on nocturnal hypoxaemia in
      Duchenne's muscular dystrophy.
AB  - The aim of this 2 yr follow-up study was to evaluate the efficacy of nocturnal
      noninvasive mechanical ventilation in a group of 10 Duchenne's muscular dystrophy
      (DMD) patients who desaturated during the night but had normal daytime blood
      gases: mean (range) age 18.3 (15-22) yrs; mean (SD) vital capacity (VC) 752.5
      (460-1,308) mL; mean time in bed (TIB) with arterial oxygen saturation (Sa,O2) <
      90% 22.8% of total TIB (range: 16.6-32.0); mean arterial oxygen tension (Pa,O2)
      10.3 (9.3-11.7) kPa (78 (70.0-87.8) mmHg); mean arterial carbon dioxide tension
      (Pa,CO2) 5.9 (4.8-6.5) kPa (44.3 (36.3-48.5) mmHg). All the patients were
      noninvasively ventilated during the night with a bilevel positive pressure
      ventilation (BiPAP) devise in spontaneous mode in order to correct the episodes
      of nocturnal desaturation. Nocturnal Sa,O2 values normalized during nocturnal
      noninvasive mechanical ventilation, and daytime sleep-disordered breathing
      disappeared, for the entire study period. No statistically significant
      differences were observed between baseline and follow-up daytime blood gas
      values, although a slight increase in Pa,O2 was found. During the follow-up, VC
      declined at a rate of 79.1 +/- 25 mL.yr-1, less than that generally reported in
      the past in untreated patients in the same age range. In conclusion, our data
      suggest that patients with advanced Duchenne's muscular dystrophy with pronounced
      nocturnal desaturation, not fulfilling criteria for imperative ventilation, could
      be successfully treated with "elective" nocturnal ventilation with immediate
      benefits consequent to the correction of the nocturnal blood gas anomalies and
      with long-term benefits related to the preservation of residual respiratory
      function, delay of development of chronic hypercapnia and thus the requirement
      for imperative mechanical ventilation.

PMID- 9632902
TI  - Corynebacterium parvum pleurodesis and survival is not significantly influenced
      by pleural pH and glucose level.
AB  - This study was carried out in the pulmonary department of a referral training
      hospital for thoracic medicine and surgery, with the aim of assessing the effects
      of pH and glucose level of a pleural effusion (PE) on survival and the response
      to pleurodesis (PD) with Corynebacterium parvum. A prospective study was carried
      out in 204 patients with recurrent, symptomatic PEs (73 benign, 131 malignant).
      Fifty eight per cent of 204 PEs had low pH (< 7.20; 7.01 +/- 0.14) nd glucose
      levels (< 60 mg.dL-1; 36 +/- 14 mg.dL-1), whereas the remaining 42% had higher pH
      (> or = 7.20; 7.36 +/- 0.07 and glucose levels (> or = 60 mg.dL-1; 79 +/- 16
      mg.dL-1). PD was attempted twice with 7 mg of C. parvum injected through chest
      tube in all patients, who were then followed up for the outcome of PD and for
      survival from the time of PD until death or the closure of the study (August
      1996). Of 204 cases, 201 were evaluable for survival and outcome of PD. In 91% of
      the low-and 82% of the high-pH/glucose benign PEs, complete PD was achieved while
      the corresponding values for the malignant PEs were 79% and 87%, respectively (p
      > 0.05). Six per cent of low-and 8% of high-pH benign PEs, and 13% of low- and 9%
      of high-pH malignant PEs were palliated with partial PD. Failures were 3% and 10%
      in the low- versus high-pH benign groups, and 8% and 4% in the low- versus high
      pH malignancies, respectively. All 201 cases maintained the immediate post-PD
      outcome throughout the follow-up. Average survival was 21.8 months in high-pH
      benign PEs versus 21.1 months in low-pH benign PEs, and 9.9 versus 8.7 months, in
      high- and low-pH malignant PEs, respectively (p > 0.05). We deduce that,
      regarding survival and the response to pleurodesis with Corynebacterium parvum,
      there is no significant difference between low- and high-pH/glucose pleural
      effusions in malignant, or benign cases.

PMID- 9632903
TI  - Autonomic dysfunction in normotensive awake subjects with obstructive sleep
      apnoea syndrome.
AB  - Obstructive sleep apnoea syndrome (OSAS) is associated with systemic arterial
      hypertension and cardiac arrhythmias and may lead to cardiovascular
      complications. Dysfunction of the autonomic nervous system (ANS) may play a role
      in the development of cardiovascular complications. The aim of this work was to
      study the ANS by spectral analysis of the heart rate variability (HRV) at rest
      and after stress (head-up tilt test) in a group of normotensive awake OSAS
      subjects. We studied 22 males with OSAS, aged 47.6 +/- 13.1 yrs, with a body mass
      index (BMI) 35.6 +/- 7.7 kg.m-2 and blood systolic and diastolic pressure (BSP
      and BDP, respectively) of 128 +/- 16 and 80 +/- 9 mmHg. Nineteen healthy males
      were studied as controls. Autonomic investigations were performed using the
      computerized power spectral analysis of HRV with autoregressive modelling which
      identifies low frequency (LF), as a marker of sympathetic activity and high
      frequency (HF), as a marker of vagal activity. OSAS patients showed greater
      sympathetic activity (LF) at rest than normal subjects, and an abnormal response
      to the head-up tilt test compared to control subjects. Five OSAS patients behaved
      like control subjects. Comparison of the functional parameters between these five
      OSAS patients and the other 17 OSAS patients showed a statistically significant
      difference for only basal arterial carbon dioxide tension (Pa,CO2) and minimal
      nocturnal oxyhaemoglobin (HbO2) saturation (NADIR). Our study shows autonomic
      nervous system dysfunction in patients with obstructive sleep apnoea syndrome,
      which may have facilitated a pathophysiological link with the cardiovascular
      complications observed in these patients.

PMID- 9632904
TI  - Lung retransplantation 3 yrs after heart-lung transplantation.
AB  - The main long-term complication after lung transplantation is chronic rejection
      in terms of obliterative bronchiolitis; when therapy does not arrest the
      progression of the airflow obstruction, lung retransplantation seems to be. at
      present, the only strategy in the management of chronic rejection. We report the
      12 month follow-up of a single lung retransplantation in a 21 yr old female who
      had received a heart-lung transplantation 35 months previously for Eisenmenger
      syndrome. The patient had excellent first allograft function and quality of life
      for 26 months, then progressively deteriorated due to the occurrence of
      obliterative bronchiolitis, and further worsened in the following 9 months. At
      that time, she underwent left lung retransplantation, based on her negative
      history of infection, low rate of acute rejection, ambulatory status, and young
      age. She is now doing well at 12 months after retransplantation and her forced
      expiratory volume in one second is still improving, p thus justifying both
      retransplantation and hopeful expectation.

PMID- 9632905
TI  - Massive pleural effusion in systemic lupus erythematosus: thoracoscopic and
      immunohistological findings.
AB  - Small to moderate, bilateral pleural effusions are common during the course of
      systemic lupus erythematosus (SLE). These are related to several complications,
      particularly, congestive heart failure, nephrotic syndrome, pulmonary embolism or
      SLE itself. Thoracoscopy performed for a massive unilateral pleural effusion in a
      patient with SLE and inferior vena cava thrombosis revealed several small nodules
      on the visceral pleura. Immunofluorescence studies of biopsy samples showed
      immunoglobulin deposits confirming the lupus-related origin of the pleuritis.

PMID- 9632906
TI  - Surveillance of tuberculosis treatment prescription in Italy. The Varese TB Study
      Group.
AB  - In industrialized countries, data on antituberculosis treatment are scanty. The
      aim of this study was to describe the tuberculosis (TB) treatment programme from
      diagnosis to drug intake in a model area of northern Italy, evaluating: 1) antiTB
      regimens prescribed and their adequacy; 2) dosage of drugs; 3) side-effects; and
      4) drug resistance. Individual data on new TB cases from all the existing health
      facilities of the area were collected by means or a prospective surveillance
      system based on the systematic review of original clinical forms. Regimens were
      classified as adequate, potentially adequate and inadequate, based on published
      recommendations. Data on drug dosage, side effects and drug resistance were
      analysed. Out of 109 TB cases with regimen recorded on clinical records, 20.2%
      included more than four major drugs, 63.3% three drugs and 16.5% two drugs. The
      regimens were classified as 1.8% adequate, 85% potentially inadequate and 12.8%
      inadequate. The dosages prescribed (mean +/- SD in mg.kg body weight-1.day-1)
      were: isoniazid: 6.8 +/- 2.7: rifampicin: 10.2 +/- 2.5; ethambutol: 21.3 +/- 4.5;
      streptomycin: 17.4 +/- 4.0: and pyrazinamide: 15.2. Twelve per cent of cases
      required treatment modification due to side-effects. Resistance to one single
      drug was found in 9% of cases, but no case with multidrug-resistant TB. The
      description of the treatment programme revealed that: 1) the majority of regimens
      are potentially adequate; 2) they are at a proper dosage; 3) the side-effects are
      in agreement with the literature; and 4) drug-resistance rates are low.

PMID- 9632907
TI  - Damp housing and asthma.
AB  - An allergic disposition has long been recognized as a risk factor for asthma.
      However, it has been suggested that, irrespective of genetic factors, exposure to
      environmental agents is of major importance in the development of asthma. In
      industrialized countries, people spend most of their time indoors and so
      environmental conditions inside the home may play an important role in asthma
      development. A review of studies examining the relationship between housing
      conditions and health in general or, more specifically, the relationship between
      respiratory symptoms/asthma and damp housing and mould has been carried out.
      These studies have shown that damp housing conditions are associated with
      increased prevalence of respiratory symptoms and asthma. The severity of asthma
      increases with an increasing quantity of dampness and mould in the home. It is
      suggested that damp conditions may, by a number of mechanisms, increase the
      allergenic burden so resulting in the development of asthma.

PMID- 9632908
TI  - Occupational asthma due to glutaraldehyde.
AB  - In recent years glutaraldehyde has emerged as the main cause of occupational
      asthma among healthcare workers. Presently glutaraldehyde is the best biocide
      agent for high-level disinfection and cold sterilization and its use has become
      widespread in hospitals. Surveillance schemes in the UK, Finland and the USA have
      reported an increasing number of cases of occupational asthma due to
      glutaraldehyde. The real magnitude of the problem is not well known as
      epidemiological studies carried out on a large scale among healthcare workers are
      not yet available. In countries where surveillance schemes are implemented,
      reports of occupational asthma cases due to glutaraldehyde should be
      circumstantiated by more diagnostic details and the diagnosis confirmed by
      objective means, to avoid an overestimation of frequency of disease. The
      pathogenetic mechanisms of occupational asthma due to glutaraldehyde are
      debatable as with other low molecular weight chemicals. A recent study has
      documented the first evidence of immunological sensitization in healthcare
      workers exposed to this chemical. Occupational asthma caused by glutaraldehyde
      can develop at levels of exposure well below the standards accepted in most
      countries. In the UK the Occupational Exposure Standard (OES) of this agent will
      be lowered from 0.2 ppm (parts of vapour per million parts of air by volume) to
      0.05 ppm. Substitution of glutaraldehyde with an alternative agent is not
      currently feasible. Intervention in the workplace and education of personnel
      handling this chemical remain irreplaceable parts of any prevention strategy.
      Early detection of disease and prompt removal of personnel from further exposure
      are the only ways of avoiding any deterioration of occupational asthma.

PMID- 9632909
TI  - Lung inflammatory response in pneumonia.
AB  - In normal conditions, alveolar macrophages (AMs) are the main cells that respond
      to bacteria that reach lower airways. However, if the microbial inoculum is too
      high or too virulent to be stopped by AM alone, these cells recruit
      polymorphonuclear neutrophils (PMN) into the alveoli from the vascular
      compartment. Cytokines, such as tumour necrosis factor-alpha (TNF-alpha),
      interleukin-1-beta (IL-beta), interleukin-6 (IL-6), and interleukin-8 (IL-8),
      secreted by the AM are able to attract PMN enhanced for phagocytosis, ready to
      destroy the invading pathogens. However, excessive cytokine production has
      deleterious effects, with a systemic inflammatory response (sepsis) that can lead
      to multiorganic failure and death. Other cytokines, such as interleukin-10 (IL
      10) balance this response, attenuating several inflammatory mechanisms. The
      inflammatory lung response in pneumonia has been well studied in animals, and
      more recently in humans, using bronchoalveolar lavage to measure some
      inflammatory mediators (TNF-alpha, IL-1 beta, IL-6, IL-8). From these studies, it
      seems that: 1) the inflammatory response to pneumonia is compartmentalized for
      most cytokines (in contrast to adult respiratory distress syndrome (ARDS)),
      except for IL-6 which is a general marker of inflammation. On the other hand, C
      reactive-protein is an acute-phase protein synthesized by the liver through the
      stimulus of IL-6 that may also be an easy-to-measure marker of inflammation that
      is directly related to IL-6; 2) some of these cytokines may be useful as
      prognostic indices; 3) there is no clear relationship between the local lung
      bacterial burden and the intensity of the inflammatory response; and 4) the
      administration of granulocyte colony-stimulating factor (G-CSF) is a promising
      therapeutic approach that is still under clinical investigation. In the future,
      it is probable that the therapeutic goal in severe pneumonia will be to find the
      exact point at which inflammation is beneficial but not deleterious. The
      measurement of the inflammatory response may serve for this purpose.

PMID- 9632910
TI  - Surfactant inactivation and surfactant therapy in acute respiratory distress
      syndrome (ARDS).
AB  - Surfactant dysfunction constitutes an important element in the complex
      pathophysiology of acute respiratory distress syndrome (ARDS). In this disease,
      surfactant may become inactivated by plasma proteins leaking into the airspaces
      as a consequence of increased alveolar permeability. In addition, surfactant
      proteins may become degraded by proteolytic enzymes or free oxygen radicals
      released by inflammatory cells recruited to the airspaces. Regardless of the
      mechanism involved, surfactant inactivation or degradation may be counterbalanced
      by increasing the pool of surfactant in the airspaces, i.e., by replacement
      therapy. Surfactant therapy has been tested with promising results in animal
      models of ARDS triggered by, e.g., lung lavage, hyperoxia or exposure to various
      toxic agents. In general, the response to surfactant treatment depends on the
      quality of the surfactant, timing of treatment in relation to the degree of lung
      injury, dosage and mode of administration. Encouraging results have been obtained
      with modified natural surfactants in clinical pilot studies on patients with
      ARDS, justifying further evaluation of this therapeutic approach in randomized
      controlled trials.

PMID- 9632911
TI  - Weaning difficulties.
AB  - All units providing ventilatory support will experience patients with weaning
      difficulties. The factors which contribute to weaning problems include the
      pathophysiology of the illness, the extent of underlying chronic disease, and
      equipment, physician-related and organisational issues. In this article ways to
      resolve these problems are outlined.

PMID- 9632912
TI  - Personal smoking habit and attitude toward smoking among the health staff of a
      general hospital.
AB  - Tobacco smoke (TS) is the single most important cause of preventable death in
      industrialized countries. Health staff have great responsibility in its control,
      but the smoking habits of health staff may influence their attitude toward
      patients. The aim of the study was to evaluate: 1) the prevalence of smoking
      among health staff at different professional levels; 2) the knowledge of smoking
      related damage; and 3) how personal smoking habits influence behaviour in the
      workplace. A questionnaire was sent to all health staff of the Morelli Hospital
      (Sondalo, Italy) asking information about age, activity, smoking habits and
      attitude toward smoking: the Fagerstrom test was also administered to smokers. A
      total of 959 valid questionnaires were collected (57% of the whole sample).
      Results were analyzed by means of Chi-squared and Student t-tests, where
      appropriate. The prevalence of smokers was 44% former smokers 24% and lifetime
      nonsmokers 32%. The highest prevalence of TS was found in nursing students and
      auxiliaries (47%) and the lowest among doctors (39%). A clear cohort-effect due
      to age was evidenced: the youngest age-group (< 30 yrs old) presents the highest
      prevalence of lifetime nonsmokers and of light smokers, and the lowest of heavy
      smokers; the oldest age-group (> 40 yrs old) presents the highest prevalence of
      quitters and of heavy smokers, and the lowest of smokers and lifetime nonsmokers;
      the intermediate age-group (31-40 yrs old) presents the highest prevalence of
      smokers. The knowledge of smoking-related damage was poor, with significant
      differences between smokers and nonsmokers and the different professional
      categories. Tobacco smoking proved to be common behaviour (even when on duty)
      among health staff. A minority of health staff seem fully aware of personal and
      social smoking related aspects. Smoking habits influence the attitude of health
      staff toward patient counselling about tobacco smoking.

PMID- 9632913
TI  - The clinical and biological impact of viral respiratory infections on the human
      airway: focus on the rhinovirus.

PMID- 9632914
TI  - A biological model to explain the association between human rhinovirus
      respiratory infections and bronchial asthma.
AB  - Human rhinoviruses (HRVs) are a frequent cause or upper respiratory tract
      infections in children and adults, and can exacerbate existing pulmonary disease.
      The major group of HRV attach to the receptor intercellular adhesion molecule
      (ICAM)-1, which is expressed on many cell types including epithelial cells. To
      study the influence of biological mediators on ICAM-1 expression, and
      consequently HRV attachment and infection, we have established an in vitro model
      system to evaluate the effects or pre-exposure to different cytokines on surface
      expression of ICAM-1 of uninfected and HRV-14-infected epithelial cells. The
      results of our studies show that the cytokines interleukin (IL)-1 beta, IL-8 and
      tumour necrosing factor (TNF)alpha increased ICAM-1 expression on epithelial
      cells. Epithelial cells infected with live HRV-14 displayed a significant
      upregulation of ICAM-1 compared to baseline. In contrast, interferon (IFN)gamma,
      whilst increasing the level of ICAM-1 expression on uninfected cells, induced a
      marked persistent downregulation of ICAM-1 expression on HRV-infected epithelial
      cells. In addition, IFN gamma appeared to completely override the ICAM-1
      upregulation induced by IL-1 beta, IL-8 and TNF alpha, during HRV infection. We
      have further demonstrated that type 2 T-helper cell (Th2)-associated cytokines,
      predominantly IL-13, induce a marked upregulation or epithelial cell surface ICAM
      1, thus increasing cellular binding sites for HRV attachment. As the airway
      mucosa or asthmatic subjects is predominantly infiltrated by activated type 2 T
      helper cells with a simultaneous decrease of type 1 T-helper cells, our
      observations could explain the increased susceptibility to human rhinovirus
      infection observed in asthma.

PMID- 9632915
TI  - Viruses and asthmatic syndromes.
AB  - Viruses are recognized to be the major cause of respiratory infections. Clinical
      and experimental evidence also supports an important role for viruses in the
      pathogenesis of lower airway disease and asthma exacerbation. In prospective
      epidemiological studies, 80% of asthma exacerbations in school-aged children and
      half of all asthma exacerbations in adults have been associated with viral upper
      respiratory infections. Human rhinovirus (HRV) has been implicated as the
      principal virus associated with asthma exacerbation. In our studies on
      respiratory viruses, we have observed two clinical patterns of presentation. The
      viruses can either be a precipitating factor of respiratory illness characterized
      by a typical clinical onset, or can induce an atypical clinical onset such as
      haemoptysis, pleuritis, spontaneous pneumothorax and asthmatic syndrome. Thus the
      observed clinicoradiological and functional features during atypical viral
      respiratory infection may be correlated to the long-term biological effects
      induced by previous and concurrent infections.

PMID- 9632916
TI  - Role of monocyte/macrophage population in immune response.
AB  - The central role of macrophages in host defence against infection and malignancy
      and processes such as atherosclerosis, makes macrophage biology a fascinating
      area for research in immunology and cell biology. The endocytic and phagocytic
      machinery of macrophages is particularly potent and their secretory potential is
      large and diverse. Studies of cell surface receptors and their role in antigen
      presentation, microbicidal and tumouricidal activity are actively researched and
      progress is now being made in defining receptors responsible for
      monocyte/macrophage cell adhesion within the immune system. This short-review
      highlights the recent advances in macrophage biology.

PMID- 9632917
TI  - Airways smooth muscle response to biological stimuli.

PMID- 9632918
TI  - Improved simulation system for routine cardiopulmonary exercise test equipment.
      Part III: A new cycle ergometer check system. ECSC Working Group on
      Standardization of Stress Test Methods.
AB  - A new check system for cycle ergometers is described. The system consists of a
      device with a calibrated reference moment which connects to the crank axle of the
      ergometer to be controlled and exerts a known amount of force. It is equipped
      with a balance system that indicates whether the force applied corresponds to the
      preset resistance of the ergometer. The power actually produced by the ergometer
      is calculated by a mathematical formula. A mechanical and an electronic version
      are described. The accuracy of the calibrator was tested: mean error during
      constant pedal revolutions per minute (rpm) conditions was < 0.59% (SD < 0.31);
      in variable rpm conditions it was < 0.645% (SD < 0.378). An isoline diagram for
      rapid clinical use is also illustrated.

PMID- 9632919
TI  - Genetics of resistance and susceptibility to mycobacterial infections.

PMID- 9632920
TI  - Recommendations and guidelines for long-term oxygen therapy (LTOT) of the
      International Respiratory Care Club (IRCC).

PMID- 9632921
TI  - [Chronic obstructive respiratory diseases: diagnosis and therapy].
AB  - It is estimated there are about one half million people suffering from chronic
      obstructive pulmonary disease (COPD) today in Hungary. Description of the disease
      and aspects of the differential procedure used in its diagnosis are here
      presented. It is crucial to provide individualized treatment for patients with
      COPD, but smoking is the most important cause of the disease; thus, quitting is
      the single intervention which can slow the progressive course of the disease. The
      author presents therapies appropriate for both the stable phase of the disease
      and its acute exacerbations. Using inhalative anticholinergs is the first step in
      the treatment schedule, with beta(2)-sympaticomimetics recommended if these are
      insufficient. The next step up the therapy ladder are the retard theophyllins;
      long-term glucocorticoids, preferentially by inhalation, may also be needed.
      Depending on the severity of an acute exacerbation of the disease, various
      antibiotics are indicated. Rehabilitation programs are detailed, with mention
      also of patient education; hopefully, such a focus will be of increasing
      importance to both physicians and patients in the near future.

PMID- 9632923
TI  - [The role and significance of the most important known cytokines in inflammatory
      bowel diseases].
AB  - Several theories have already been postulated in connection with the pathogenesis
      of inflammatory bowel diseases, yet none of them has been approved. Recently
      increasing attention has been payed to different cytokines, playing central role
      in the development of inflammatory processes. In the intestinal mucosa of
      patients suffering from inflammatory bowel diseases increasing amounts of
      interleukin-1 (IL-1), tumor necrosis factor (TNF) and platelet activating factor
      (PAF) could be measured. On the other hand, antiinflammatory cytokines seem to be
      ineffective, or being present in insufficient amount (IL-4 and IL-10
      respectively). It is therefore probable, that altered ratios of cytokines, or
      pathologic regulation of their production lead to progression of inflammation in
      IBD. Influence of cytokine production may open new therapeutic approach, e.g. IL
      10 enema proved to be effective in the treatment of some cases of steroid
      resistant ulcerative colitis, while intravenous administration was useful in
      Crohn's disease. A brief, comprehensive review of our present knowledge about
      cytokines in IBD is given.

PMID- 9632922
TI  - [Closure of the patent ductus arteriosus by means of cardiac catheterization].
AB  - Authors report their results with transcatheter closure of patent arterial duct
      during a period of 1 year. Thirty patients underwent the procedure at the mean
      age of 5.22 yrs (range 5 mos-22.3 yrs) and mean bodyweight of 19.1 kg (range 5.8
      73 kg). There were 9 males and 21 females. The diagnosis of the patent arterial
      duct was established by physical examination and noninvasive techniques. The
      procedures were attempted in all patients above 5 kg bodyweight with patent
      arterial duct and normal pulmonary artery pressure, irrespective of the shunt
      size. All procedures were performed under general anesthesia in one session with
      the diagnostic cardiac catheterisation. Transcatheter closure was successful in
      29 patients. In one patient the device embolized into the left pulmonary artery,
      snaring was unsuccessful, surgical closure of the patent duct and removal of the
      device took place uneventfully. Control aortography 15 minutes after the coil
      placement showed insignificant residual shunt through the patent duct in 8
      patients (27%), while echocardiography at 1 month proved complete closure in all.
      The patients were followed by noninvasive methods. No mortality was observed.
      Authors emphasize the low risk and cost-effectiveness of the procedure. They
      stress the importance of the patients selection. Authors applied the technique
      for the first time and introduced it to the regular patient-care practice in
      Hungary.

PMID- 9632924
TI  - [Evaluation of a complex trace element composition and bioutilization using
      isotope technics and total body measurement].
AB  - Modified mineral and trace element solutions were prepared containing Zn-65, Co
      57, Mn-54, Fe-59, Mo-99 and Ni-63 isotopes which were physico-chemically
      identical to the original solution. Bioutilization examinations were carried out
      on animals receiving their normal feeding, after p. os application of complex
      trace element composition (CTEC) namely whole-body retention studies, bioassays,
      scintigraphic and excretion examinations in altogether 180 Wistar rats, 6 Beagle
      and 2 mongrel dogs using whole body counter, gamma and beta counters, gamma
      camera and metabolic cages. Extremely high whole body retention was measured in
      case of iron (8-30%), high utilizations in case of zinc (4-5%), cobalt (4-6%),
      molybdenum (3-4%) and manganese (2-4%) and a lower value in case of nickel.
      Bioassay and scintigraphic evaluations showed marked liver-, kidney-, and muscle
      and moderated blood uptakes. The way of excretion was mainly (more than 90%) via
      the faeces in case of zinc, manganese, iron and nickel, although cobalt excreted
      in 8% and molybdenum in 52% via the urinary tract. Our results show, that isotope
      technique combined with whole body counting and excretion studies in an available
      method for trace element bioutilization studies.

PMID- 9632925
TI  - [CD30 positive large T-cell primary cutaneous lymphoma].
AB  - The primary cutaneous CD30 positive large cell lymphoma is a rare tumor, confined
      to the skin. The characteristic clinical picture is a large, often exulcerating
      sometimes spontan regressing tumor or nodule. Dense infiltration of large,
      anaplastic or non-anaplastic T or non T, non B cell of the dermis is
      characteristic. Generalization, lymph node or internal manifestation is rare, the
      prognosis is favourable. A 25-year-old male patient is presented, in whom
      generalised skin symptoms-itching, reddish-brownish papules with central necrosis
      developed. Two years later general symptoms-fever, fatigue, lymph node and spleen
      enlargement, increased in white blood cell count with prominent eosinophilia,
      increase in CD4 number occurred. The histology and immunohistology of the skin
      and peripheral lymph node showed large, anaplastic, CD30 positive T cell
      infiltration. CHOP, then BACOP treatment resulted in regression of the skin and
      the internal symptoms.

PMID- 9632926
TI  - Cellular mechanisms of temperature sensitivity in hypothalamic neurons.

PMID- 9632927
TI  - Cell biology and the functions of thermosensitive neurons in the brain.

PMID- 9632928
TI  - Spinal neuronal thermosensitivity in vivo and in vitro in relation to
      hypothalamic neuronal thermosensitivity.
AB  - In the spinal cord, temperature signals are generated which serve as specific
      inputs in the central nervous control of body temperature. Because of the
      spatially distinct organization of afferent and efferent neuronal systems at the
      spinal level, the afferent pathway for temperature signal transmission could be
      identified in vivo in the ascending, anterior and lateral tracts with a
      relationship of about 75:25% between warm and cold sensitive neuraxons. Analysis
      of spinal neuronal thermosensitivity in vitro on spinal cord tissue slices has
      been concerned, so far, with the superficial laminae of the dorsal horn as the
      site of origin of ascending nerve fibers conveying mostly temperature and pain
      signals, and with lamina X as a site of origin of afferent as well as efferent
      neurons. A relationship of about 95:5% between warm and cold sensitive neurons
      was found at the segmental level, indicating that warm sensitivity is the
      prevailing, primary property of spinal neurons, whereas cold sensitivity seems to
      be mainly generated by synaptic interaction as a secondary modality. Dynamic
      responses to temperature changes were frequently displayed in vitro at the spinal
      segmental level in lamina I + II but not in lamina X, even by neurons whose
      static activity was little influenced by local temperature. Dynamic
      thermosensitivity was found less frequently in ascending tract neuraxons and was
      not observed in hypothalamic neurons receiving temperature signal inputs from the
      spinal cord, and thus, does not seem to be relevant for the thermosensory
      function of spinal cord neurons, unlike peripheral warm and cold receptors. A
      majority of spinal warm sensitive neurons displayed both static and dynamic warm
      sensitivity as an inherent property after synaptic blockade. In the further
      analysis of spinal cord thermosensitivity, the in vitro approach permits
      application of the same electrophysiological and neuropharmacological methods as
      were established for the analysis of hypothalamic thermosensitivity. In addition,
      the topography of the spinal cord will provide additional structural and possibly
      histochemical information to characterize the functions of neurons independently
      of their thermal properties.

PMID- 9632929
TI  - Neuronal networks controlling thermoregulatory effectors.

PMID- 9632930
TI  - Plasticity of hypothalamic temperature-sensitive neurons.

PMID- 9632931
TI  - Role of nitric oxide in temperature regulation.

PMID- 9632932
TI  - Pathophysiology of opioids in hyperthermic states.

PMID- 9632933
TI  - Prostaglandins and fever.

PMID- 9632935
TI  - Biogenic amines and thermoregulatory changes.
AB  - This review recapitulates the general principles of the organization of the
      thermoregulatory system, describes the thermoregulatory reactions of small and
      large mammals to hot environment and analyzes the probable roles of biogenic
      amines in these responses. Catecholamines found in peripheral blood plasma or
      excreted in urine represent a spillover of mediators released partly from
      sympathetic nerve endings and partly from the adrenal medulla. Since the
      thermoregulatory efforts differ between small and large mammals in cold and hot
      environments, the peripheral release of catecholamines is also different in these
      animals. The levels of these signal substances in the blood, as well as their
      peripheral metabolic and functional effects, serve as feedback signals for the
      hypothalamic integrative circuitry. The roles of antagonistic modulatory
      monoaminergic systems, ascending from the lower brain stem to the hypothalamus,
      in these integrations were discussed only partly, because this was a topic of
      another recent review (Zeisberger and Roth, 1996).

PMID- 9632934
TI  - Brain eicosanoids and LPS fever: species and age differences.
AB  - The results of the present study, summarized in Table 2, demonstrate that
      different species and strains of rodents (rats and mice) and birds (chickens)
      exhibit rather specific fever response. Systemic administration of LPS caused
      monophasic elevation in Tb of chickens, biphasic changes in Tb of rats (initial
      drop followed by an increase in Tb), whereas mice failed to develop hyperthermia
      and responded by a decreased Tb. The LPS-induced alterations in hypothalamic
      prostanoid synthesis were also rather species-specific and differ markedly even
      between the two strains of mice. We failed to find a common direct correlation
      between LPS-induced changes in Tb and hypothalamic prostanoid production in
      rodents (rats and mice). This observation is supported by our recent study on age
      related changes in fever response in rats, where we found that hypothalami of LPS
      treated old and young adult rats produced similar amounts of PGE2 and PGI2, in
      spite of more pronounced and prolonged hypothermia, and a delayed elevation in Tb
      of old rats, as compared with young (Fraifeld et al., 1995b). Moreover, the
      hypothalamus of febrile chickens did not display any detectable activation of
      PGE2 production, suggesting that PGE2 is not a common central mediator of fever
      in homeotherms (Fraifeld et al., 1995a). Apparently, the actual body temperature
      not always reflects the functional state of central thermostat, and increased
      PGE2 production in hypothalamus would not directly, at least in rodents, lead to
      body temperature elevation. Furthermore, peripheral effects, including PG
      mediated ones, of pyrogens can interfere and even overcome their centrally
      mediated effects (Morimoto et al., 1991; Burysek et al., 1993). Previously, we
      have shown that no additional elevation in hypothalamic PGE2 production occurs in
      response to doses of LPS over 10 micrograms in rats and 25 micrograms in mice,
      while the increased doses led to further changes in Tb response (Kaplanski et
      al., 1993). Morimoto et al. (1991) have considered that PGE2 acts centrally to
      cause fever and peripherally to cause hypothermia, and, hence, these opposing
      actions, both being induced by LPS, may act together to determine the final
      thermoregulatory response. Other possibilities could be related to counterbalance
      of endogenous antipyretics (Kluger, 1991; Kozak et al., 1995), that may occur not
      only at the level of thermoregulatory center but also outside the CNS (Klir et
      al., 1995), and to the existence of PG-independent mechanisms of LPS fever. The
      latter have been shown for IL-8 (Rothwell et al., 1990; Zampronio et al., 1994)
      and MIP-1 (Davatelis et al., 1989; Minano et al., 1990; Hayashi et al., 1995;
      Lopez-Valpuesta and Myers, 1995), which are, apparently, mediated via CRF
      (Strijbos et al., 1992; Zampronio et al., 1994), and INF-alpha, mediated via the
      opioid receptor mechanisms (Hori et al., 1991, 1992). However, it has been shown
      recently that in different species the same pyrogenic cytokines (IL-8) may
      induced fever via different, PG-independent (in rats; Zampronio et al., 1994) or
      PG-dependent (in rabbits; Zampronio et al., 1995) mechanisms. It should be noted
      that fever response is not always accompanied by an elevation in Tb. The final
      effect of pyrogens on body temperature depends upon the balance between heat
      production and heat loss, which in turn is highly dependent upon body size and
      ambient temperature, especially in small animals. Perhaps, the hypothermic
      response observed in our mice and rats at 22 degrees C may be in part attributed
      to ambient temperature, which was below a thermoneutral zone. The reduced febrile
      response is considered, at least in part, to contribute to an increased mortality
      and prolonged recovery from infections (Kluger, 1986). From this point, it is
      difficult to suggest whether the hypothermia observed in our mice and rats could
      be of somewhat adaptive significance. It has been shown that at the ambient
      temperature of 30 degrees C, Swiss Webster mice can re

PMID- 9632936
TI  - Immunological and neuroendocrine modulation of fever in stress.

PMID- 9632937
TI  - The effects of drugs on thermoregulation during exposure to hot environments.

PMID- 9632938
TI  - Heat shock protein response in the central nervous system following hyperthermia.

PMID- 9632939
TI  - Glial reactions in the central nervous system following heat stress.

PMID- 9632940
TI  - Prostaglandin system in the brain: sites of biosynthesis and sites of action
      under normal and hyperthermic states.

PMID- 9632941
TI  - Nitric oxide and carbon monoxide in the brain pathology of heat stress.

PMID- 9632942
TI  - Hyperthermia and the central nervous system.

PMID- 9632943
TI  - Pathophysiology of brain edema and cell changes following hyperthermic brain
      injury.

PMID- 9632944
TI  - Blood-brain barrier permeability during hyperthermia.

PMID- 9632945
TI  - Cytokines and blood-brain barrier permeability.

PMID- 9632946
TI  - Nerve thermal injury.

PMID- 9632947
TI  - Fever and antipyresis.

PMID- 9632948
TI  - Regional differentiation of sympathetic efferents during fever.

PMID- 9632949
TI  - Thermoregulation and body fluid in hot environment.

PMID- 9632950
TI  - [Psychological psychotherapy--the beginning of a new era?].

PMID- 9632951
TI  - [Affect and mimetic behavior].
AB  - The relationship between facial expression and experienced affect presents many
      problems. The two diametrically opposed positions proposing solutions to this
      problem are exemplified using the conceptions of Mandler u. Izard. The underlying
      premises of both conceptions still prevail in various forms. The authors reject
      the concepts according to which facial expression is merely correlated to the
      affects (see Mandler 1975) as well as the view that facial expression controls
      the affects (see Izard 1977). The relationship between affect and facial
      expression is reexamined, subjecting it to a semiotic, essentially semantic
      analysis similar to the Ogden and Richards' language and meaning approach. This
      analysis involves a critical discussion of Scherer's attempt of a purely
      communicational interpretation using Buhler's organon model. In the author's
      approach, facial expression is seen not simply as a system of signals, but as a
      system of representative signs which signify the affects and refer to the emotive
      meaning of things for the subject. The authors develop the thesis that human
      beings are not born simply with the ability to speak, but also with the abstract
      possibility of performing facial expressions. This ability develops by way of
      coordinating patterns of expressions, which are presumably phylogenetically
      determined, with affects that take on a socially determined individual form,
      similar to language acquisition during socialisation. The authors discuss the
      methodological implications arising for studies investigating the affective
      meaning of facial expressions.

PMID- 9632952
TI  - [Alexithymia and automatic activation of emotional-evaluative information].
AB  - The emotional valence of stimuli seems to be stored in the associative network
      and is automatically activated on the mere observation of a stimulus. A principal
      characteristic of alexithymia represents the difficulty to symbolize emotions
      verbally. The present study examines the relationship between the dimensions of
      the alexithymia construct and emotional priming effects in a word-word paradigma.
      The 20-Item Toronto Alexithymia Scale was administered to 32 subjects along with
      two word reading tasks as measures of emotional and semantic priming effects. The
      subscale "difficulty describing feelings" correlated as expected negatively with
      the negative inhibition effect. The subscale "externally oriented thinking"
      tended to correlate negatively with the negative facilitation effect. Thus, these
      dimensions of alexithymia are inversely related to the degree of automatic
      emotional priming. In summary, there is evidence for an impaired structural
      integration of emotion and language in persons with difficulties in describing
      feelings. Poor "symbolization" of emotions in alexithymia is discussed from a
      cognitive perspective.

PMID- 9632953
TI  - [Problems and goals of psychotherapy patients. A qualitative-content analytic
      study of patient statements at initial assessment].
AB  - The present paper has the objective of demonstrating the content-analytical
      assessment of problems reported by the patient and of his expectations in respect
      of psychotherapeutic treatment. In this approach of qualitative research, the
      interpretation process is split up into several steps which can be tested with
      regard to their adequacy to the material. This reduces the range of subjective
      interpretations. The development of the analysis of content is described in
      detail. First of all, a system of categories was outlined on the basis of
      patients' Nos. 1-40. This system was then used to rate the texts Nos. 41-80 and
      modified. After that, the revised version was applied to rate the texts Nos. 81
      120, and so on. As can be shown, high interrater reliabilities were achieved by
      this procedure. The coding of the entire sample of n = 198 patient reports
      yielded the following results. Of all problems, depressive complaints, bodily
      complaints, anxiety and interpersonal problems were most frequent. The most
      important goals concerned coping with anxiety, gaining joy of
      living/happiness/satisfaction, greater self-assertion, better family
      relations/partnership, coping with problems and peace of mind/calmness. The
      categories of goals (18 items) seemed to be more complex and manifold than the
      categories of problems (10 items) and went beyond mere reduction of complaints or
      problems. As was to be expected, differences between diagnostic groups with
      regard to frequency of problems and expectations could be demonstrated. However,
      these differences were found only in the frequencies of deficits (complaints and
      problems) and reduction of complaints or coping with problems, respectively,
      whereas positive, health-related goals did not seem to be specific to the
      disorder. This suggests that it would be worth while to utilise patients'
      subjective definitions of problems and goals for assessment schedules to evaluate
      treatment outcomes.

PMID- 9632954
TI  - [Interdisciplinary longitudinal curriculum "Medical Psychology, Psychotherapy and
      Psychosomatics." Experiences from the preclinical segment].
AB  - The departments of Medical Psychology, Psychosomatics and Psychotherapy developed
      an interdisciplinary longitudinal curriculum in order to coach medical students
      for the whole length of their medical education. Experiences from the first four
      undergraduate semesters are reported. 46 students (33 females, 13 males), mean
      age 22.3 +/- 2.6 years, attended 60 hours of interdisciplinary group sessions.
      Frequent motives to join the course were interest in psychosocial disciplines and
      relevant previous experience. The students expected to benefit from this project
      in their study, their future practice as a physician, and in their personal
      development. Important educational goals that could be attained were the adoption
      of a patient-centred view in medicine as well as strengthening of the students'
      critical capacities and sensitivity. The students especially appreciated the
      possibility of group discussions and the opportunity to participate actively in
      the course. Based on a critical review of the evaluation, the possibility of a
      transfer of our model is considered and perspectives for the future are
      developed.

PMID- 9632955
TI  - Impact of molecular biology on diagnosis and management of arrhythmogenic
      disorders.

PMID- 9632956
TI  - Does obesity influence ciprofibrate activity?
AB  - STUDY OBJECTIVE: The association of obesity and dyslipidemia, namely high
      triglycerides and low HDL-cholesterol levels, is well known, but, as far as we
      are aware, the possible influence of obesity on the efficacy of current
      hypolipidemic drugs has never been studied. Therefore, we investigated the
      relationship between obesity and ciprofibrate efficacy. METHODS: This was a post
      hoc analysis of an open-label study with 6-month therapy of ciprofibrate carried
      out in the Atherosclerosis Out-Patient Clinic of Coimbra University Hospital.
      Eligible patients were 30 to 70 years old with cholesterol > 6.2 mmol L-1 and/or
      triglycerides > 2.23 mmol L-1. A sequential sample of 20 patients was selected
      but only 18 completed the study. After at least one month of diet or washout
      period all participants were given 100 mg day-1 of ciprofibrate. Triglycerides,
      total (TC) and HDL-cholesterol (HDL-C), apoproteins A-1, B100 and (a), and
      fibrinogen were measured at the beginning and at the end of the study. LDL
      cholesterol (LDL-C) was calculated by the Friedewald formula. MAIN RESULTS:
      Baseline and the percentage of modification with ciprofibrate (delta%) of
      triglycerides correlated positively with body mass index (BMI) and waist/hip
      ratio (WHR). Baseline HDL-C correlated negatively with BMI and WHR, but delta%
      correlated positively with BMI. Fibrinogen behaved differently from
      triglycerides. The negative correlations between BMI and WHR and the delta% of
      LDL-C lost power and significance in stepwise regression after the introduction
      of types of dyslipidemias as an independent variable. CONCLUSIONS: Ciprofibrate
      may be particularly effective in obese patients with high triglycerides and low
      HDL-C, a subject deserving further research.

PMID- 9632957
TI  - [Cardiac troponin-T. Diagnostic efficacy in acute myocardial infarction. Clinical
      and laboratory assessment].
AB  - Cardiac troponin-T is a subunit of the myofibrillar regulatory
      troponintropomiosin complex, with sufficient specificity to myocardium. In normal
      conditions it is absent from serum and its presence indicates lesion of the
      cardiac cells. The authors evaluated the analytical and clinical performance of
      an immunoassay for cardiac troponin-T, before its introduction in their own
      laboratory routine. They concluded that the test had good analytical performance,
      with some difficulties in practicability that can be surpassed by using a rapid
      bedside test for troponin-T in urgency departments, already approved by FDA in
      USA and available in Portugal. The diagnostic specificity and sensitivity was
      better than the one of the classic enzymatic markers for Acute Myocardial
      Infarction (AMI) but it is necessary to establish clear clinical protocols that
      allow its use in AMI.

PMID- 9632958
TI  - [Significance of family assessment and biological markers in the prevention of
      arterial hypertension].
AB  - OBJECTIVE: To verify the predictability of the appearance of hypertension through
      the clinical history and biological markers. POPULATION: Consisted of 300
      Portuguese Caucasian individuals, M = 130 and F = 170, between the ages 18 and
      85, including 90 pregnant women. METHODS: Blood pressure was measured in every
      individual, and questions were made concerning personal and familiar hypertensive
      background. The serum renin activity, the active renin, serum endoxin, and the
      urinary aldosteron, free dopamine, c--AMP, and noradrenalin were checked. The
      analysis of the results was carried ou using the Student's T Test and de chi(2)
      method. RESULTS AND CONCLUSIONS: Hypertensive parents lead to the development of
      hypertension on their descendants; the averages of diastolic blood pressure in
      normotensive individuals are higher when parents are hypertensive, compared with
      normotensive, seeming that a possible genetic factor may be implied in the
      involvement of the vessels. Normotensive young masculine adultshave higher
      average systolic blood pressure when their fathers are hypertensive, than those
      whose fathers have normal blood pressure levels; as far as young women are
      concerned, we verified that the mother's genetic influence seems to be relevant
      in the appearance of higher blood pressure levels in their daughters during
      pregnancy, contributing to think hat man and women may have genetically different
      factors to determine blood pressure levels. We also verified that young adults
      with normal levels of blood pressure, whose parents suffer from high blood
      pressure, present significantly higher levels of serum renin activity than a
      similar group of young adults whose parents have normal blood pressure. We
      concluded that the family history and the measuring of the blood pressure even at
      young adults may contribute for the forecasting of high blood pressure, as is the
      evaluation of biological parameters, particularly in those who have family
      history of hypertension. Serum renin activity may be a possible biological marker
      for the forecast of the future development of high blood pressure.

PMID- 9632959
TI  - [Role of auxiliary diagnostic tests in the clarification of the etiology of
      syncope: experience at an arrhythmia center].
AB  - Syncope is a syndrome caused by a reversible reduction of blood to the brain.
      Three hemodynamic abnormalities can cause syncope: an acute decrease in cardiac
      output, an acute increase in cerebrovascular resistance and a fall in systemic
      blood pressure due to ineffective control of peripheral vascular resistance. We
      made a retrospective study of 121 patients with syncope history, 67 males, and 57
      females, with mean age 48 +/- 14 years, and at least six months of clinical
      follow-up. Twelve patients had valvular disease, two patients had hypertrophic
      cardiomyopathy, eight patients had dilated cardiomyopathy, 14 patients had
      ischemic disease, three patients had congenital disease; 82 patients did not have
      cardiac disease. Syncope etiology was arrhythmic in 69 patients: 47 patients had
      tachyarrhythmia (supraventricular--in 27 patients and ventricular in 20 patients)
      and 15 patients had bradyarrhythmia (seven patients had sinus node disease and
      eight patients had atrioventricular block). Non arrhythmic etiology of syncope
      was identified in 29 patients (neurologic disease--ten patients, metabolic
      disease--one patient and iatrogenic--two patients; vasodepressor syncope--14
      patients, and hypertrophic cardiomyopathy--two patients). It was not possible to
      determine the syncope etiology in 30 patients. The assessment of patients who
      present syncope depends on establishing the basis for the symptoms. The initial
      step is differentiating patients with normal cardiovascular systems from those
      with heart disease. In the former, tilt-table testing proved to be the most
      productive from a diagnostic perspective; in the latter group, electrophysiologic
      evaluation was the most elucidative from a diagnostic perspective. The ultimate
      goal is to obtain a sufficiently strong correlation between syncopal symptoms and
      detected abnormalities to permit an accurate assessment of prognosis and to
      develop an effective treatment plan. CONCLUSIONS: It is very important to
      establish the etiology of syncope for optimal management of patients and it is
      therefore possible to control the symptoms in the majority of them. The patients
      who present syncope require a complete history and a physical examination for an
      appropriate workup to be initiated. Tilt-table testing was the most accurate for
      the diagnosis of vasodepressor syncope while electrophysiologic testing provides
      an accurate method for assessing the etiology of tachyarrhythmic syncope.

PMID- 9632960
TI  - [Syncope in a patient with Ebstein's anomaly and Wolff-Parkinson-White syndrome].
AB  - We describe a clinical case of a patient with Ebstein's anomaly and syncope in
      Wolff-Parkinson-White's syndrome. After a radiofrequency ablation of an accessory
      atrioventricular pathway there was a different arrhythmia of ventricular origin.
      Although we have some doubts about their clinical relevance, we discuss the
      complex arrhythmic background, the medical management difficulties and the
      prognostic issues. There is an evaluation about ablation usefulness in this
      context regarding future attitudes in relation to other kinds of rhythm disorder.

PMID- 9632961
TI  - [Atrial fibrillation surgery using intraoperative radiofrequency].
AB  - Radiofrequency ablation is successful in most supraventricular tachyarrhythmias
      and the first results in percutaneous applications in atrial fibrillation have
      been published. At present, all the surgical techniques for the treatment of
      atrial fibrillation use extensive atrial incisions. A case report is presented of
      a 67 year old woman with chronic atrial fibrillation and rheumatic mitral and
      tricuspid valve disease. At surgery, pulmonary vein isolation was performed using
      a continuous linear ablation around the pulmonary veins, instead of using
      extensive atrial incisions. Concommitantly, a mitral valve replacement and
      tricuspid valve annuloplasty were performed. Five months after surgery, the
      patient remains with a stable sinus rhythm surgery and in functional class I
      (NYHA).

PMID- 9632962
TI  - [Isomorfic forms of apolipoprotein (A) and their relationship with coronary
      disease].

PMID- 9632963
TI  - The silent revolution in childhood cancer.

PMID- 9632964
TI  - Medicine and the pharmaceutical industry: what's right, what's wrong, and what's
      to come.

PMID- 9632965
TI  - Intramural tubal polyps--a villain in the shadows?
AB  - BACKGROUND: Intramural tubal polyps are commonly described in association with
      subfertility. However, there is unfamiliarity among clinicians about the
      investigations available for making a diagnosis of this condition. The objective
      of this paper was to highlight the suitable investigations for diagnosis and thus
      increase awareness of this condition and its relationship with subfertility.
      METHOD: A retrospective review of 14 patients with intramural tubal polyps was
      done for the period from January to December 1996. An attempt was made to
      correlate the radiographic findings on hysterosalpingography with transvaginal
      ultrasound examinations and hydrochromotubation performed under laparoscopic
      observation. The fertility history of these patients was also examined. RESULTS:
      The review demonstrated a prevalence of 3.8% of intramural tubal polyps in a
      selected population of predominantly subfertile women. Only hysterosalpingography
      was useful in making the diagnosis in-vivo. Fifty percent of the patients did not
      have any other obvious pathology to explain their subfertility. CONCLUSION: We
      conclude that meticulous hysterosalpingography is useful as a diagnostic
      investigation and that consistent reporting is needed for good follow-up.

PMID- 9632966
TI  - The use of semi-quantitative urine test-strip (Micral Test) for microalbuminuria
      screening in patients with diabetes mellitus.
AB  - BACKGROUND: Microalbuminuria is an early marker of prognostic significance in
      diabetic renal disease. However, testing for microalbuminuria in a timed sample
      of urine using the double antibody radioimmunoassay (RIA) method is cumbersome
      and requires special laboratory facilities. Recently, a test strip for
      microalbuminuria, the Micral Test was available and we evaluated the performance
      of this test strip as a screening method for detection of microalbuminuria.
      METHODS: One hundred consecutive diabetic patients who were tested to be dipstick
      negative (Albustix) for proteinuria were enrolled for the study. Micral Tests
      were performed on a paired first morning and random urine specimen from the same
      patient and the results compared with a timed 24-hour urine measurement of urine
      albumin excretion using the RIA method. RESULTS: Eighteen specimens were tested
      positive by the RIA method with a urinary albumin range of 32-177 mg/24 hours.
      With the Micral Test, the following sensitivity, specificity, positive and
      negative predictive values were obtained: 66.7%. 97.6%, 85.7% and 93.0% for the
      first morning urine specimens, and 77.8%, 91.5%, 66.7% and 94.9% for the random
      urine specimens. CONCLUSIONS: These results suggest that Micral Test with either
      the first morning or random urine specimen offers a simple, reliable, rapid and
      convenient method for screening of microalbuminuria in the diabetic patient.

PMID- 9632967
TI  - Registration of new blindness in Singapore for 1985-1995.
AB  - Data on causes of blindness in Singapore from blind registration have been
      gathered yearly since 1950, when blind registration in Singapore was first
      started. The blind register is maintained by the Singapore Association of the
      Visually Handicapped (SAVH), based on reports from practising ophthalmologists in
      the government institutions. Ophthalmologists in the private sector (who also
      attend to the bulk of patients coming from overseas) do not register their blind
      patients. During the past four decades (from 1950 till 1990), analyses of our
      causes of blindness have been published by various local authors, quoting data
      from the blind register at the SAVH. These reports showed that our pattern of
      blindness reflected predictably the trend already observed in the developed
      countries, viz a shift from infections to congenital and age-related causes. This
      trend is in keeping with the impact of affluence on the economic and social
      environment, resulting in better health services and the prevention of avoidable
      diseases. Updated but hitherto unpublished new blind registrations in Singapore
      for 1985-1995 confirm the now established trend. As of now (in 1995), retinal
      diseases is the ranking cause (57.6%), followed by congenital and developmental
      disorders (14.7%), optic atrophy (9.3%), glaucoma (8.6%) and minor causes (1%).

PMID- 9632968
TI  - Traumatic posterior fossa extradural haematomas (PFEDH).
AB  - OBJECTIVES: While posterior fossa extradural haematomas (PFEDH) may lead to rapid
      neurological deterioration and death because of brainstem compression, prompt
      treatment often leads to a good outcome. The non-specific clinical signs and the
      rarity of this lesion in craniocerebral trauma adds to the difficulty in
      diagnosis. The aim of this study was to identify features which could lead to an
      early diagnosis. METHODS: Seventeen patients with posterior fossa extradural
      haematomas were operated on over 4 1/2 years, accounting for 7.5% of the 226
      surgically operated extradural haematomas in the Department of Neurosurgery, Tan
      Tock Seng Hospital, Singapore. Four patients were excluded from this study due to
      non-availability of the case records. The remaining 13 patients formed the study
      group in this retrospective analysis. RESULTS: The majority of cases (77%)
      presented acutely within 24 hours. The mechanism of injury varied from a fall in
      7 cases, a road traffic accident in 4 cases and assault in 2. Nine patients had
      evidence of external injury to the occiput, 8 patients had skull fractures, and
      diastasis of the lambdoid suture was seen in 2 cases. Presence of aerocele was
      noted in the CT scan of 4 cases. All 9 cases admitted with a high GCS score of
      more than 8 had a very good outcome. CONCLUSION: An early CT scan head is
      recommended if a combination of the following features is present: occipital soft
      tissue injury, drowsiness, occipital fracture or diastasis of the lambdoid
      suture.

PMID- 9632969
TI  - Difficult tracheal intubation--analysis and management in 37 cases.
AB  - AIM: To analyse the anatomical features of difficult airways encountered during
      general anaesthesia and study how difficult intubation was circumvented during
      anaesthesia in our local population. METHOD: Difficult intubation was defined as
      failure to visualise the larynx during laryngoscopy after neck flexion and
      external cricoid pressure was applied. All cases of difficult intubation
      collected over 1 1/2 years during general anaesthesia were recorded prospectively
      and analysed. RESULTS: Thirty-seven cases of difficult intubation were identified
      among 5,379 cases of general anaesthesia requiring endotracheal intubation. 40.5%
      of the cases were not expected to be difficult pre-operatively. 5.4% of the cases
      were Lehane II, 91.9% Lehane III and 2.7% Lehane IV. The anatomical features
      encountered included receding chin, limited mouth opening, limited neck
      extension, abnormal dentition, short thyromental distance, large tongue,
      supraglottic mass and floppy epiglottis. Gum elastic bougie was commonly used to
      overcome the intubation difficulties. Laryngeal mask, blind nasal tracheal
      intubation, fiberoptic bronchoscopic intubation and sometimes an alternative
      anaesthetic technique, such as regional anaesthesia, were resorted to.
      CONCLUSION: Assessment of multiple anatomical features would improve prediction
      of difficult intubation. Assessment of receding chin, neck extension, mouth
      opening, teeth, tongue size, thyromental distance might pick up 81% of difficult
      airways. Unexpected problems with epiglottis and glottic inlet are the potential
      sources of danger that are difficult to predict pre-operatively.

PMID- 9632971
TI  - "I've got a UFO stuck in my throat!"--an interesting case of foreign body
      impaction in the oesophagus.
AB  - This is a case report of an elderly lady with odynophagia because she
      accidentally swallowed a tablet which was still wrapped in its blister pack. A
      discussion of foreign body ingestion, particularly in the elderly, is included.
      To the authors' knowledge, this is the first paper that includes a lateral
      cervical radiograph of an ingested blister pack.

PMID- 9632970
TI  - Complicated varicella zoster infection in 8 paediatric patients and review of
      literature.
AB  - BACKGROUND: This is a study of complicated varicella zoster infection in
      paediatric patients. AIM: To find out the number of patients with such
      complications, the types of complications and their outcome. METHOD: This
      involved a retrospective review of the case records of 8 patients who presented
      to our unit over a 12-month period (Jan-Dec 96). All patients were previously
      well without any underlying immunodeficiency. Varicella zoster (VZ) infection was
      confirmed by VZ immunofluorescence from vesicular fluid. RESULTS: CMS
      complications accounted for 6 of the 8 cases. Of these, 3 presented with
      encephalitis, 2 with cerebella ataxia and 1 with aseptic meningitis and cerebella
      ataxia. Of the non-CNS cases, 1 presented with glomerulonephritis with
      superimposed staphylococcus infection of skin ulcers; the other had disseminated
      VZ infection with haemorrhagic vesicles, hepatitis, ileus with mesenteric
      adenitis and disseminated intravascular coagulation. OUTCOME: The patient with
      disseminated VZ infection and multiple organ involvement died 5 days after a
      stormy course. One patient with encephalitis who had status epilepticus for 2
      hours had behavioural problems and poor memory. The remaining 6 patients had no
      sequelae. CONCLUSION: VZ infection usually a minor illness, can result in serious
      life-threatening complications in previously healthy patients.

PMID- 9632972
TI  - Prolonged cutaneous sequelae after intra-arterial injection of propofol.
AB  - Propofol is a popular drug for the induction of anaesthesia and sedation in the
      intensive care. Previous cases of inadvertent intra-arterial injection propofol
      injection have had no more than a few hours of hyperaemia. However in this case,
      residual cutaneous hyperaemia for 12 days were found after intra-arterial
      injection. This report also highlights the presence of an aberrant radial artery
      at a site that is used commonly for intravenous cannulation. Early suspicion
      should be aroused if the patient complains of pain on injection that is not
      abolished by lignocaine and if blanching of the hand is seen on injection. A
      useful precaution is establishing a running intravenous line before the
      administration of drugs. The literature concerning prevention and treatment of
      inadvertent intra-arterial injection is discussed.

PMID- 9632973
TI  - Occupational asthma caused by orangutan in a zoo animal handler.
AB  - A zoo animal handler developed bronchial asthma for the first time from handling
      orangutans (Pongo pygmaes). He had prior allergic reactions (rhinoconjunctivitis
      and urticarial rash), but no asthma, to deer and other hoofed animals in the zoo.
      In a worksite challenge, immediate and late onset of asthmatic symptoms and
      airflow obstruction were provoked by carrying a baby orangutan for about 20
      minutes.

PMID- 9632974
TI  - Amineptine and midazolam dependence.
AB  - A case report of a patient with amineptine and midazolam dependence is presented.
      A literature search was done for other cases of amineptine abuse and their
      presentations and medical investigations are compared. This is the first locally
      reported case of amineptine abuse and highlights the fact that amineptine is a
      potential drug of abuse.

PMID- 9632975
TI  - The current understanding of continence and defecation.
AB  - Problems of continence and defecation are encountered in all facets of medical
      practice. Yet, the anorectum is cloaked by misunderstanding. Recent research has
      shed new light on this subject and newer concepts based on systematic
      investigations have paved the way to a rational approach. Motor function of the
      anorectum can now be delineated by manometry, electromyography and nerve
      stimulation. More complex functions like the coordination for continence and
      defecation are measured using other studies including defecating proctography,
      scintigraphic balloon topography, scintigraphic evacuation and colonic transit.
      The amalgamation of data from these studies have led to a logical sequence for
      the maintenance of normal continence and defecation that is developed in this
      manuscript based on our current understanding of anorectal motility and
      physiology. This allows patients who are resistant to straightforward diagnosis
      to be selected for specialised tests resulting in categorisation and a rational
      management strategy for their problems.

PMID- 9632976
TI  - Electrocardiographic case: an interesting case of cardiomegaly and pulmonary
      hypertension. Atrial septal defect (ASO) with Eisenmenger syndrome.

PMID- 9632977
TI  - What you need to know: interpreting hepatitis B viral markers.

PMID- 9632978
TI  - AIDS 1998. Virology: overview.

PMID- 9632979
TI  - Recent advances and remaining problems in HIV assembly.

PMID- 9632980
TI  - Chemokines and coreceptors in HIV/SIV-host interactions.

PMID- 9632981
TI  - In vivo detection and quantitation of HIV in blood and tissues.

PMID- 9632983
TI  - HIV heterogeneity and disease progression in AIDS: a model of continuous virus
      adaptation.

PMID- 9632982
TI  - The gastrointestinal tract and the pathogenesis of AIDS.

PMID- 9632984
TI  - AIDS 1998. Epidemiology: overview.

PMID- 9632985
TI  - Declines in AIDS incidence and deaths in the USA: a signal change in the
      epidemic.

PMID- 9632986
TI  - Diversity of the HIV/AIDS epidemic in Europe.

PMID- 9632987
TI  - Can HIV epidemics among injection drug users be prevented?

PMID- 9632988
TI  - Prevention of HIV transmission by blood transfusion in the developing world:
      achievements and continuing challenges.
AB  - In industrialized countries, the use of sensitive HIV screening tests, donor
      deferral, and more conservative use of blood have resulted in a dramatic decrease
      in the transmission of HIV infection by blood transfusion. The risk of HIV
      transmission in the USA by blood screened negative for HIV antibody was recently
      estimated at one in 440,000-660,000 donations. Despite this low risk, continued
      public concern has compelled blood collection agencies and policy makers to
      continue to search for more sensitive HIV screening tests. Genome amplification
      techniques are receiving increased attention and are being piloted in Germany.
      HIV-1 p24 antigen testing was implemented in the USA in March 1996. In the first
      18 months of p24 antigen testing, an estimated 18 million blood donations were
      tested at a cost of US$90 million to detect three antigen-positive, antibody
      negative donations. However, in many developing countries where severe anemia is
      widespread and the prevalence of HIV infection among blood donors is orders of
      magnitude greater than in industrialized countries, the blood supply is either
      incompletely screened or not screened at all for HIV antibody. Although the
      contribution of transfusion-transmitted infection to the HIV epidemic has not
      been accurately assessed, an estimated 5-10% of HIV infections in developing
      countries are due to blood transfusion. In a study conducted 1 year after
      implementation of HIV blood screening in the largest hospital in the capital city
      of the Democratic Republic of the Congo, an estimated 25% of pediatric HIV
      infections, and 40% of infections among children over 1 years of age, were due to
      transfusion. Lack of commitment by national governments and international aid
      organizations to this fundamental element of HIV prevention has resulted in a
      shortage of basic equipment, supplies, and trained personnel for blood screening.
      Moreover, provision of test kits alone cannot prevent HIV transmission by
      transfusion in resource-poor areas. More comprehensive programs are needed to
      improve the recruitment and retention of safe donors, essential laboratory
      services for blood banking and screening, technical training and supervision,
      appropriate use of transfusions, and the prevention of severe anemia. This
      article summarizes the steps being taken by developing countries to prevent HIV
      transmission by blood transfusion, lessons learned, and the work that still lies
      ahead.

PMID- 9632989
TI  - Genetic and immunological host factors associated with susceptibility to HIV-1
      infection.
AB  - The probability of HIV transmission depends on the interplay of many different
      factors related to infectiousness of the HIV-infected partner, susceptibility of
      the HIV-uninfected partner, and biological characteristics of HIV strains. Here,
      we review recent studies of host immunological and genetic factors which may
      affect susceptibility to HIV-1 infection. These factors are summarized in Table
      1. We propose how to explore biological correlates of susceptibility to HIV-1
      infection in epidemiological studies, discuss the strengths and limitations of
      this research, and address the implications for public health.

PMID- 9632990
TI  - AIDS 1998. Vaccines and immunology: overview.

PMID- 9632991
TI  - Antigen presentation and related immunological aspects of HIV-1 vaccines.

PMID- 9632992
TI  - Cellular immune responses to HIV-1.

PMID- 9632993
TI  - Humoral immunity to HIV, SIV, and SHIV.

PMID- 9632994
TI  - AIDS vaccine development in primate models.

PMID- 9632995
TI  - Alternative, cytokine-mediated host defense mechanisms against HIV infection: the
      concept of self-limitation of HIV replication.

PMID- 9632996
TI  - AIDS 1998. Clinical treatment: overview.

PMID- 9632997
TI  - Trial design in the era of highly effective antiviral drug combinations for HIV
      infection.

PMID- 9632998
TI  - Altered natural history of AIDS-related opportunistic infections in the era of
      potent combination antiretroviral therapy.
AB  - Since potent HIV protease inhibitor drugs became widely available in early 1996,
      many HIV clinical specialists have noted a marked decrease in the occurrence of
      AIDS-related opportunistic infections, and some specialists have reported unusual
      clinical presentations and manifestations of previously common opportunistic
      infections. In this article, we will review (1) the available data regarding
      recent trends in AIDS-related opportunistic infections incidence and
      manifestations, (2) clinical and immunologic evidence that potent combination
      antiretroviral therapy can alter the natural history of these opportunistic
      infections, and (3) the implications of these findings for current patient
      management practice and future clinical and immunologic research. As a preface to
      this review, however, it is important to acknowledge that any evaluation of the
      potential benefit of potent combination antiretroviral therapy in reducing the
      risk of serious opportunistic infections can be confounded by the concomitant use
      of prophylactic antimicrobial agents co-administered to prevent specific
      opportunistic infections. For example, it is standard clinical practice to
      administer trimethoprim-sulfamethoxazole (or another agent if trimethoprim
      sulfamethoxazole cannot be tolerated) to patients with an absolute CD4 lymphocyte
      count < 200 cells/microliters, unexplained chronic fever or a history of
      oropharyngeal candidiasis. Similarly, specific antimicrobial prophylaxis to
      prevent disseminated Mycobacterium avium complex (MAC) infection in patients with
      absolute CD4 counts < 50 cells/microliters is also a widely recommended
      guideline. Although the relative efficacies of specific antimicrobial prophylaxis
      regimens in preventing the most common life- and sight-threatening opportunistic
      infectious complications of AIDS [Pneumocystis carinii pneumonia (PCP),
      disseminated MAC infection, and cytomegalovirus (CMV) retinitis] are now well
      established, these relative efficacies were established in the era before potent
      combination antiretroviral therapies became available and may not be
      generalizable to the current era. Nevertheless, for perspective, the reported
      efficacies of prophylaxis for PCP, disseminated MAC infection, and CMV end-organ
      disease are summarized in Table 1.

PMID- 9632999
TI  - New antiretrovirals and new combinations.
AB  - The appearance in the clinic of two to three new antiretroviral agents yearly
      since 1995 has permitted unprecedented advances in HIV treatment. This remarkable
      pace of drug development is a testimony to an extraordinary international effort
      involving scientists, clinicians, governments, community activists and industry
      dedicated to the rapid and safe development of novel therapies. New drugs present
      the opportunity to improve HIV therapy. They also create an enormous challenge to
      the clinician, who must constantly assimilate data on new drugs and incorporate
      this information into practical management strategies. Combination therapy has
      proven the most effective approach to treat HIV disease. The profound and
      sustained viral suppression achievable with combinations such as indinavir (IDV),
      lamivudine (3TC) and zidovudine (ZDV) have resulted in a dramatic shift in HIV
      treatment paradigms over the last year. The full potential of combination therapy
      with available drugs has yet to be realized as only a limited number of the
      possible combinations incorporating new drugs have been fully tested. Even drugs
      available for many years may have untapped potential. Didanosine (ddI) and
      stavudine (d4T), once thought to be contraindicated in combination because of
      their overlapping peripheral neuropathy toxicity, have proven well tolerated and
      effective. Combination therapy can increase antiviral suppression, prevent drug
      resistance, optimize drug exposure and simplify dosing, but it can also result in
      pharmacologic antagonism, subtherapeutic drug concentrations and unexpected
      toxicities. Clinical studies have confirmed in vitro studies showing
      pharmacologic antagonism for the combination of ZDV and d4T. Combining protease
      inhibitors with each other or with non-nucleoside reverse transcriptase
      inhibitors is complicated by effects both classes of drugs have on drug
      metabolism and clearance. These observations underline the importance of
      carefully conducted clinical studies to characterize safety, pharmacokinetics and
      efficacy of combination therapies. In this review, we will first summarize the
      clinical profile of new drugs which either became commercially available last
      year [nelfinavir, nevirapine, delavirdine (DLV)] or are in the late stages of
      clinical development (DMP-266, abacavir and 141W94). Later we will summarize new
      data on nucleoside, protease inhibitor and non-nucleoside reverse transcriptase
      combination regimens. Finally, we will briefly mention new drugs in early stages
      of development.

PMID- 9633001
TI  - Antiretroviral therapy: where are we?

PMID- 9633000
TI  - Can HIV be eradicated?

PMID- 9633002
TI  - AIDS 1998. Social, cultural and political aspects: overview.

PMID- 9633003
TI  - Focus and effectiveness of HIV-prevention efforts for young people.

PMID- 9633004
TI  - Preventive interventions to reduce heterosexual HIV risk for women: current
      perspectives, future directions.

PMID- 9633005
TI  - Recent HIV-prevention interventions for gay men: individual, small-group and
      community-based studies.

PMID- 9633006
TI  - Measuring harm reduction: the effects of needle and syringe exchange programs and
      methadone maintenance on the ecology of HIV.

PMID- 9633007
TI  - Systematic review on the cost-effectiveness of public health interventions for
      HIV prevention in industrialized countries.
AB  - OBJECTIVE: Systematic review on cost-effectiveness of public health interventions
      for primary HIV-prevention programs. DESIGN: Rating of publications using the
      guidelines for economic studies in medicine of the British Medical Journal
      Economic Evaluation Working Party. METHODS: Studies with defined nondrug
      intervention, defined study population, identifiable method of analysis and at
      least one endpoint for evaluation of intervention were included. One publication
      could consist of more than one study. Methods to generate effectiveness data,
      inclusion of human costs and kind of outcome parameters for economic evaluation
      were documented. To avoid bias in performing the review, the British Medical
      Journal guidelines were applied. Cost-effectiveness data were reviewed according
      to outcome parameters used in economic evaluation. RESULTS: Forty studies were
      identified in 34 publications, 30/40 from the United States and 22 supported by
      public funding; only five studies were directed to men who have sex with men,
      intravenous drug users and persons with HIV-infected partners. Screening programs
      and counseling with testing accounted for 30/40 studies. Complete research
      question (intervention and outcome) was presented in 29/40 studies (72.5%).
      Thirty-four studies were conducted from the societal perspective and the
      viewpoint was clearly stated in 31/40 studies. Incremental analysis was performed
      in 21 studies, correction for inflation in two and discounting when appropriate
      in 23/29 studies; sensitivity analysis was performed in 23/40. Effectiveness data
      were presented in 38 studies. Diagnosis of previously unknown HIV infection (n =
      11), sexual (n = 7) and vertical transmission (n = 6), infection of patients by
      healthcare workers and life years saved (both n = 6) served as the most common
      outcome parameters. In 21 studies, human costs were included in the estimation of
      costs (52.5%) and nine studies used the human capital approach. Cost
      effectiveness data revealed costs between US$460 and US$1.2 million per case of
      previously unknown HIV infection prevented, strongly depending on prevalence.
      Studies on sexual and vertical transmission demonstrated lower costs when the
      benefits of treatment were included. Costs for 1 life-year saved varied between
      $29,000 and $458,000. CONCLUSIONS: The British Medical Journal guidelines for
      economic analysis in medicine are a feasible instrument for systematic reviews of
      cost-effectiveness studies on primary HIV infection. The quality of published
      studies varies widely. A clear definition of outcome parameters as an object of
      economic evaluation can be regarded as crucial, besides incremental analysis,
      discounting, and inclusion of human costs. Further work is needed to develop and
      evaluate a specific rating system for cost-effectiveness analysis in this field.

PMID- 9633008
TI  - Rat urinary chemiluminescence: effect of ethanol and/or hexachlorobenzene uptake.
AB  - Hexachlorobenzene (HCB) administration to rats induces porphyria cutanea tarda,
      characterized by high levels of urinary porphyrins (> 40 micrograms/day) and
      accumulation of highly carboxylated porphyrins in liver (> 15 micrograms/g of
      tissue). Ethanol administration, under the conditions employed, was not
      porphyrinogenic and was able to diminish some of the responses elicited by HCB.
      Furthermore, ethanol and/or HCB administration leads to organ disturbances that
      involve oxidative stress. We have measured the changes in urinary
      chemiluminescence (CL) levels, as part of a systematic evaluation of the
      metabolic alterations in rats chronically treated with ethanol and/or HCB. The
      results, that constitute the first set of urinary CL data obtained from an animal
      model system, indicate that the measurement of the spontaneous urinary CL can
      constitute a fast, simple and sensitive method to evaluate disturbances
      associated with oxidative stress.

PMID- 9633009
TI  - Changes of structure and energy on the route from dioxetane to carbonyl products.
      A quantum chemical study.
AB  - Energy diagrams, changes of geometry and bond orders were calculated semi
      empirically for the thermolysis of 1,2-dioxetane. Stretching of the O-O bond,
      then of the C-C bond and distortion of the whole quadrangular structure make
      major, but different, contributions to the reaction coordinate on the path to
      formaldehyde. The activation barrier represents a vast region where the gaps
      between the ground and excited states are small, and this favours horizontal
      radiationless transitions leading to the excitation of a product. The results
      show that semi-empirical calculations may help to provide better insight into the
      nature and mechanism of the chemiluminescence excitation.

PMID- 9633010
TI  - Phenol derivatives as enhancers and inhibitors of luminol-H2O2-horseradish
      peroxidase chemiluminescence.
AB  - Systematic studies on phenol derivatives facilitates an explanation of the
      enhancement or inhibition of the luminol-H2O2-horseradish peroxidase system
      chemiluminescence. Factors that govern the enhancement are the one-electron
      reduction potentials of the phenoxy radicals (PhO./PhOH) vs. luminol radicals
      (L./LH-) and the reaction rates of the phenol derivatives with the compounds of
      horseradish peroxidase (HRP-I and HRP-II). Only compounds with radicals with a
      similar or greater reduction potential than luminol at pH 8.5 (0.8V) can act as
      enhancers. Radicals with reduction potentials lower than luminol behave in a
      different way, because they destroy luminol radicals and inhibit
      chemiluminescence. The relations between the reduction potential, reaction rates
      and the Hammett constant of the substituent in a phenol suggest that 4
      substituted phenols with Hammett constants (sigma) for their substituents similar
      or greater than 0.20 are enhancers of the luminol-H2O2-horseradish peroxidase
      chemiluminescence. In contrast, those phenols substituted in position 4 for
      substituents with Hammett constants (sigma) lower than 0.20 are inhibitors of
      chemiluminescence. On the basis of these studies, the structure of possible new
      enhancers was predicted.

PMID- 9633011
TI  - Stopped-flow analysis of Ru(bpy)3(3+) chemiluminescent reactions.
AB  - The stopped-flow technique was employed to measure chemiluminescent emission from
      the reaction of a mixture of oxalate and proline with a chemiluminescence
      reagent, tris(2,2'-bipyridine) ruthenium(III), or Ru(bpy)3(3+) is a versatile
      reagent and is often used in bioanalytical applications, including the detection
      of certain drugs and their metabolites, for example. Unfortunately, Ru(bpy)3(3+)
      has not yet been fully examined as a possible chemiluminescence reagent for
      simultaneous kinetic determinations. In this work, a differential reaction rate
      method, based on simple least squares regressions of the pseudo-first order decay
      data, was used to resolve two compounds, oxalate and proline, reacting
      simultaneously with Ru(bpy)3(3+). Our results indicate that stopped-flow analyses
      with Ru(bpy)3(3+) could provide a viable method for simultaneous determinations
      of unresolvable analytes of environmental and pharmaceutical importance.

PMID- 9633012
TI  - Pro-inflammatory response of alveolar macrophages induced by sulphite: studies
      with lucigenin-dependent chemiluminescence.
AB  - Alveolar macrophages (AM) were studied for their capability to release mediators
      involved in modulation of neutrophil (PMN) functions. Initial responses were
      induced by sulphite. Supernatants obtained from canine, human and rat AM pre
      treated with sulphite in concentrations of 0.1-2 mmol/L enhanced the respiratory
      burst of canine, human and rat PMN, measured by lucigenin-dependent
      chemiluminescence (CL). This PMN-stimulating activity exhibited platelet
      activating factor (PAF)-like properties, as indicated by desensitization of the
      PAF receptor, inhibition with PAF antagonists WEB 2086 and CV 3988, and the
      kinetic CL response like PAF after chloroform extraction of supernatants
      inhibitable by PAF antagonist CV 3988. These results indicate that AM are
      triggered by sulphite to release mediators that activate the respiratory burst of
      PMN, primarily via the PAF receptor.

PMID- 9633013
TI  - Photographic detection of fluorescent-labelled oligodeoxynucleotide in the
      blotting format by peroxyoxalate chemiluminescence.
AB  - The preparation of a fluorescent labelled oligonucleotide and its photographic
      detection by peroxyoxalate chemiluminescence (PO-CL) are described. Fluorescent
      labelling of an oligonucleotide (15-mer) was performed with naphthalene-2,3
      dicarboxaldehyde to give an N-substituted 1-cyanobenz[f]isoindole (CBI)
      derivative (CBI-15-mer). For the photographic detection of CBI-15-mer, the
      bis(2,6-difluorophenyl) oxalate (DFPO)-dimethyl phthalate (DMP) system was
      selected to obtain a long-lived CL emission. After optimizing the conditions for
      the CL reaction, the system was applied to the photographic detection, and as
      little as 250 fmol per spot of CBI-15-mer on a membrane were detected as a
      visible spot with an instant photographic film.

PMID- 9633014
TI  - Immune complex transfer two-site chemiluminescent immunoassay for serum growth
      hormone in alevin chum salmon.
AB  - An immune complex transfer two-site chemiluminescent immunoassay (CLIA) for
      salmon growth hormone (GH) was developed to measure serum GH in alevin chum
      salmon (Oncorhynchus keta) using a chemiluminescent acridinium ester as a label.
      The immune complex transfer method dramatically reduced non-specifically bound of
      acridinium ester labelled antibody without a decrease in the specific binding.
      Consequently, we could detect lower levels of GH than achieved previously in a
      two-site CLIA for salmon GH. The detection limit of the assay was 7.8 fg/ml and
      the standard curve was linear up to 250 fg/ml. Coefficients of variation were 2.2
      7.7% within-assay and 5.3-91% between-assay. We have developed a highly sensitive
      and reproducible GH method and applied it to measurement of GH in alevin chum
      salmon.

PMID- 9633015
TI  - Ultrasensitive in vivo bioassay detects bioactive human growth hormone in
      transduced primary human keratinocytes.
AB  - An improved in vivo body weight gain bioassay for the potency determination of
      human growth hormone (hGH) has been set up in "little" mice (lit/lit), a mutant
      derived from the C57BL/6J strain. This improved assay now has a detection limit
      of the order of 0.05 micrograms/mouse/day, which corresponds to a sensitivity
      about 20-fold higher than that of the most sensitive in vivo assay reported up to
      now: the tibia test in hypophysectomized rats or mice. This sensitivity was
      achieved mainly by introduction of a careful pre-assay selection and of a three
      injections per day schedule. The utilization of these conditions in a 2x2
      factorial assay design allowed the potency determination of recombinant DNA
      derived hGH (rec-hGH) in bacterial extracts with acceptable accuracy and
      precision, together with the greatest economy of material, only 0.24 mg of
      unknown and standard hormone preparation being sufficient for an entire 10-animal
      assay. This contrasts to a minimum of 2.7 mg that are necessary for an economical
      assay in hypophysectomized rats. The same assay procedure was also used to
      demonstrate the in vivo bioactivity of hGH secreted into a culture medium from
      transduced human primary keratinocytes. The growth curve constructed with n = 8
      little mice presented a highly significant correlation (r = 0.939, p < 0.001) and
      a slope = 0.016 g/mouse/day. It was thus possible to prove, for the first time,
      the in vivo bioactivity of rec-hGH secreted by transplantable human epidermal
      cells, utilized as an experimental model for somatic gene therapy.

PMID- 9633016
TI  - 5-HT3 serotonergic receptor mediation of hypoglycemia-induced arginine
      vasopressin but not oxytocin secretion in normal men.
AB  - The present study was undertaken in order to establish the possible involvement
      of 5-HT3 serotonergic receptors in the control of basal and/or hypoglycemia
      stimulated arginine vasopressin (AVP) and/or oxytocin (OT) secretion. For this
      purpose, 12 normal men were injected intravenously with a bolus of 4 mg
      ondansetron, a specific 5-HT3 receptor antagonist, under basal conditions (n = 6)
      or 30 min before insulin (0.15 IU/kg body weight) administration (n = 6) (insulin
      tolerance test (ITT)). Control experiments with normal saline instead of
      ondansetron treatment were performed. Furthermore, on a different occasion, the
      same subjects were tested in identical experimental conditions with 8 mg
      ondansetron. Our results showed that the hypoglycemic response to insulin was
      similar during the ITT and ondansetron plus ITT. Inhibition of 5-HT3 serotonergic
      receptors with ondansetron (4 or 8 mg) did not modify the basal secretion of AVP
      and OT and the OT response to insulin-induced hypoglycemia. In contrast, the
      administration of 4 or 8 mg ondansetron significantly reduced in a similar manner
      hypoglycemia-induced AVP rise. Mean peak level at 45 min after insulin injection
      was 2.25 times higher than baseline in the control ITT and 1.5 times higher than
      basal value in the ondansetron (4 or 8 mg) plus ITT. These data demonstrate that
      5-HT3 serotonergic receptors at least partially mediate the AVP response to
      hypoglycemia, without modifying the simultaneous OT response. On the other hand,
      5-HT3 receptors do not appear to be involved in the control of basal posterior
      pituitary hormone secretions.

PMID- 9633017
TI  - Persistent endocrine stress response in patients undergoing cardiac surgery.
AB  - To investigate the endocrine stress response in patients undergoing major surgery
      with general anesthesia using a balanced technique with sufentanil, isoflurane
      and midazolam up to the second postoperative day, blood levels of cortisol,
      epinephrine, norepinephrine, prolactin and growth hormone were determined in 68
      males for elective coronary artery bypass grafting (CABG) surgery.
      Intraoperatively, during extracorporeal circulation none of the measured
      parameters were significantly increased compared to preoperative values. The
      endocrine response of patients with perioperative epinephrine medication (n = 32)
      was not significant different to patients that did not receive exogenous
      epinephrine (n = 36). On the evening of the day of surgery, levels of cortisol (3
      fold), epinephrine (4.7 fold), norepinephrine (1.7 fold) and growth hormone (16.5
      fold) were significantly increased. Compared to preoperative values levels of
      cortisol (3.3 fold), growth hormone (5.5 fold) and norepinephrine (1.8 fold)
      remained elevated up to the evening of the second postoperative day. In
      conclusion, the endocrine stress response in patients undergoing CABG-surgery
      under general anesthesia with sufentanil, midazolam, isoflurane is
      intraoperatively prevented by anesthesia. Although hemodilution or hormone
      degradation might be responsible for the lack of an increase in endocrine
      parameters during CPB, this study indicates that a balanced technique with
      isoflurane, sufentanil and midazolam is more effective in blocking the endocrine
      stress response than previously described anesthetic techniques. In the early
      postoperative period, a sharp increase in cortisol, epinephrine, norepinephrine
      and growth hormone occurred suggesting that the predominant endocrine stress
      response begins in the intensive care unit with end of anesthesia. The
      postoperative elevated levels of cortisol, growth hormone and norepinephrine
      indicate a persisting stress-response for more than two days after surgical
      trauma.

PMID- 9633018
TI  - Plasma somatostatin-like immunoreactivity and somatostatin-28 levels in obese
      men.
AB  - Somatostatin (SS) impairs nutrient absorption. It has been suggested that
      hyposomatostatinaemia may be involved in the pathogenesis of obesity. However,
      data on postprandial SS-like immunoreactivity (SLI) levels in obese subjects are
      controversial and the levels of SS-28, the main molecular form of circulating SLI
      in healthy subjects, have not been determined. To characterise the fasting and
      postprandial plasma pattern of SLI and SS-28 in obese men, we studied eight obese
      men (age 24-32 yr, BMI 33-42 kg/m2), with normal glucose tolerance test and
      normal gastric emptying of solids, and eight healthy men (age 24-39 yr, BMI 21-24
      kg/m2). Blood samples were taken at regular intervals in fasting conditions and
      for 2 h after a standard solid-liquid meal (2.3 MJ). Plasma SLI and SS-28 were
      measured by RIA. Our results showed that fasting and postprandial plasma SLI and
      SS-28 levels were not significantly different in healthy and obese subjects. In
      conclusion SS-28 is the predominant form of circulating SLI in obese subjects.
      The normal pattern of fasting and postprandial plasma SLI and SS-28 levels in
      such subjects suggests that somatostatin does not have a pathogenetic role in
      obesity.

PMID- 9633019
TI  - Heart-rate variability for discrimination of different types of neuropathy in
      patients with insulin-dependent diabetes mellitus.
AB  - It has been shown that patients with insulin-dependent diabetes mellitus (IDDM)
      may reveal abnormal alterations in heart-rate variability (HRV) due to autonomic
      neuropathy. This study was performed to prove whether heart-rate variability can
      be used to stratify diabetic patients with different types of neuropathy. 48
      patients with IDDM (age 17-64 yr) underwent standard function tests to assess
      autonomic and peripheral neuropathy. According to the results of these tests they
      were divided into 4 groups: Group 1: 18 patients without autonomic or peripheral
      neuropathy. Group 2: 13 patients with peripheral neuropathy. Group 3: 7 patients
      with autonomic neuropathy. Group 4: 9 patients with autonomic and peripheral
      neuropathy. HRV was measured by continuous 24-hours monitoring and time domain
      parameters were calculated. The results were compared with sex and age-matched
      healthy controls according to the individual characteristics of the groups and
      among each subgroup. Our results showed that in Group 1 there was a significant
      difference of time domain parameters indicative of parasympathetic influence,
      i.e. rMSSD and pNN50 in comparison to the control subjects (p = 0.002, p =
      0.008). These results depended on the duration of diabetes; a subgroup of
      patients with a duration of IDDM of less than 2 years had no significant
      differences of HRV values. Group 2 showed the same significant differences. Group
      3 and 4 showed significant differences in all measured time domain variables
      (SDNN, SDANN, SDNN index, rMSSD and pNN50) in comparison to the control subjects
      (p < 0.04). A comparison of group 1 with group 2 offered significant differences
      in rMSSD and pNN50 (p = 0.004, p = 0.003). Comparing group 1 with group 3 and 4,
      all HRV parameters showed significant differences (p < 0.03). In conclusion, HRV
      is able to distinguish between patients with different types of neuropathy
      depending on the involvement of parasympathetic or more sympathetic influenced
      parameters. Furthermore, this method is able to unmask early manifestations of
      neurological disorders prior to their detection by neurological function tests.

PMID- 9633020
TI  - Bone turnover is reduced in children with juvenile rheumatoid arthritis.
AB  - Juvenile Rheumatoid Arthritis (JRA) is frequently associated with osteoporosis.
      In order to determine if JRA osteoporosis is related to reduced formation or to
      increased bone resorption or both, serum levels of calcium (Ca), phosphorus
      (PO4), magnesium (Mg), alkaline phosphatase (ALP), parathormone (PTHi), 25
      hydroxyvitamin D3 (25-OHD) and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D),
      osteocalcin (OT), carboxyterminal propeptide (P-coll-1-c), and carboxyterminal
      telopeptide of type I collagen (ICTP) were evaluated in 47 JRA children, 33 with
      active disease and 14 in remission. The therapy consisted of nonsteroidal
      antiinflammatory (NSAIDs) drugs in pauciarticular subset, NSAIDs and Methotrexate
      (MTX) in polyarticular, NSAIDs and steroids in systemic onset. OT reflects bone
      formation, P-coll-1-c reflects collagen production and bone formation, ICTP,
      marker of collagen degradation in bone, indicates bone destruction. Serum levels
      of Ca, PO4, Mg, ALP, PTHi 25-OHD and 1,25-(OH)2D were comparable in JRA children
      and in controls. OT (8.7 +/- 3.7 ng/ml vs 9.6 +/- 5.1), P-coll-1-c (301.2 +/-
      118.4 ng/ml vs 264.1 +/- 100.1) and ICTP (15.7 +/- 5.7 ng/ml vs 16.1 +/- 6.1) did
      not differ statistically in the whole group of JRA children vs controls. OT (8.0
      +/- 3.5 vs 10.4 +/- 3.8) and ICTP (14.4 +/- 5.4 vs 18.8 +/- 5.4) were
      significantly lower in active than inactive group. In polyarticular and systemic
      onset OT and ICTP were significantly lower than in pauciarticular. No difference
      was found in active patients treated with steroids vs active patients treated
      with NSAIDS and NSAIDs plus MTX. The lower serum levels of OT and ICTP in active
      disease support the hypothesis that both bone formation and resorption are
      reduced in JRA bone turnover.

PMID- 9633021
TI  - Peritoneal fluid levels of immunoreactive corticotropin-releasing factor (CRF)
      and CRF-binding protein (CRF-BP) in healthy and endometriosic women.
AB  - Corticotropin-releasing factor (CRF) is a 41-amino acid neurohormone involved in
      the neuroendocrine response to stress, also playing a role in cell-mediated
      immune functions and in inflammation. In the light of recent evidence showing an
      association between endometriosis and altered cellular immunity factors, the
      present study investigates immunoreactive (ir) CRF in the peritoneal fluid of
      healthy women, and in patients with pelvic adhesions and endometriosis. In
      addition, peritoneal fluid concentrations of CRF-binding protein (CRF-BP), a 37
      kDA protein of 322 amino acids able to modulate central and peripheral CRF
      functions, were evaluated. Peritoneal fluid samples (n = 35) were collected from
      healthy women (n = 12), from patients with intrapelvic adhesions (n = 8), and
      from women with endometriosis (n = 15). In the control group a specimen of blood
      was collected. Peritoneal fluid and plasma CRF levels were measured by a two-site
      immunoradiometric assay (IRMA), and CRF-BP levels were measured by a specific
      radioimmunoassay (RIA). CRF and CRF-BP levels in peritoneal fluid were lower than
      plasma values, and independent of the phase of the menstrual cycle: in
      particular, in healthy women there was no significant difference between
      peritoneal fluid and plasma CRF-BP levels during two phases of the menstrual
      cycle. Peritoneal fluid levels of CRF and CRF-BP were similar in healthy patients
      and women with pelvic adhesions or with endometriosis, and when patients with
      adhesions or with endometriosis were considered as single group, no difference in
      CRF and CRF-BP levels was noted in comparison to the control group. In patients
      with endometriosis, no significant differences in peritoneal fluid CRF or CRF-BP
      levels were recorded, although in patients with stage 2 and stage 3 of the
      disease peritoneal fluid CRF-BP levels were higher than in healthy patients or in
      those with a lower grade of the disease. These results suggest that the
      peritoneal concentration of these hormones may reflect the circulating levels:
      the absence of any significative variations in peritoneal fluid CRF levels
      according to the degree of the endometriosis, suggests a limited role of CRF in
      the immunological changes related to the disease

PMID- 9633022
TI  - Parathyroid hormone suppression by 22-oxacalcitriol in the severe parathyroid
      hyperplasia.
AB  - The suppression of parathyroid hormone (PTH) secretion by the administration of
      1,25-dihydroxyvitamin D [1,25(OH)2D3] and 22-oxacalcitriol (OCT) was evaluated in
      nude mice transplanted with human hyperplastic parathyroid tissue. The
      parathyroid tissue was obtained for transplantation from a patient with severe
      secondary hyperparathyroidism who had undergone a parathyroidectomy. Tissue
      specimens were transplanted into the gluteus muscle of female nude mice. Animals
      were divided into two groups; one group was fed a normal diet, and the other
      group was fed a low calcium diet during the administration of OCT and
      1,25(OH)2D3. OCT and 1,25(OH)2D3 were intraperitoneally administered two times
      every week, for a total of eight times. Serum calcium and phosphate levels were
      significantly higher in the mouse administered 1,25(OH)2D3 than in the mouse
      administered OCT. Serum alkaline phosphatase activity was elevated similarly in
      the mouse administered either OCT or 1,25(OH)2D3. OCT strongly suppressed human
      PTH secretion from the graft in mice with normal serum calcium levels as did
      1,25(OH)2D3. However, human PTH secretion from the graft was stimulated by the
      administration of a low-calcium diet, despite OCT and 1,25(OH)2D3 administration.
      In summary, OCT and 1,25(OH)2D3 suppress PTH secretion even from severe secondary
      hyperplastic parathyroid tissue only in mice with normal or high calcium serum
      levels.

PMID- 9633023
TI  - Immunodetection of manganese superoxide dismutase in cultured human retroocular
      fibroblasts using sera directed against the thyrotropin receptor.
AB  - The identification of antigenic targets in the retroocular autoimmune response of
      Graves' ophthalmopathy is likely to increase our understanding of mechanisms
      underlying this disorder. While a number of putative autoantigens have been
      identified on the basis of molecular weight or cell of origin, a determination of
      the significance of these antigens is contingent upon an identification of the
      amino acid sequence. Our group has previously identified immunoreactive
      retroocular fibroblast (ROF) proteins recognized by thyrotropin receptor (hTSH-R)
      antisera (anti-p1), at molecular weights of 95, 71, 41, and 14-25 kDa. In the
      present study, proteins detected by anti-p1 and visualized by Ponceau staining
      were isolated and processed for microsequencing. Ponceau staining revealed dense
      bands at molecular weights of 14 and 23 kDa, and a weak band at 41 kDa. N
      terminal sequencing was performed on the prominent band at approximately 23 kDa,
      showing it to be manganese superoxide dismutase (MnSOD), a mitochondrial enzyme
      responsible for protection against oxygen free radical-associated cellular
      damage. Sequence comparison of MnSOD to the hTSH-R peptide, p1, revealed a linear
      segment of amino acid homology. Preincubation of anti-p1 with p1 blocked
      immunodetection of the 23 kDa band corresponding to MnSOD, and
      immunoprecipitation of ROF protein using anti-pi yielded protein recognized by
      anti-MnSOD. Autoimmunity against human recombinant MnSOD was further assessed by
      ELISA. Patients with Graves' disease (n = 53) had significantly higher ELISA
      indices than normal control subjects (n = 29), while patients with Hashimoto's
      thyroiditis had intermediate values. These results document MnSOD autoantibodies
      in patients with Graves' disease and suggest that this may result from an immune
      cross-reactivity between MnSOD and the TSH-receptor.

PMID- 9633024
TI  - Effects of 3-month nifedipine treatment on endocrine-metabolic parameters in
      patients with abdominal obesity and mild hypertension.
AB  - It is widely accepted that abdominal obesity presents with exaggerated insulin
      secretion, insulin resistance and a trend toward glucose intolerance.
      Hypertension is frequently associated to abdominal obesity, and hyperinsulinism
      could play a role in its pathogenesis. Some studies reported that Ca-antagonists
      positively influence insulin sensitivity and glucose tolerance in obese patients
      with normal or elevated blood pressure. However, other studies reported worsening
      of metabolic balance during treatment with Ca-antagonists in hypertensive non
      insulin-dependent diabetes mellitus (NIDDM) patients and in normal subjects. We
      studied 19 patients with abdominal obesity, mild hypertension and insulin
      resistance on balanced, mild hypocaloric diet (1400 Kcal), to verify the effects
      of the Ca-antagonist nifedipine on both basal and oral glucose tolerance test
      (OGTT)-induced glucose and insulin levels as well as on IGF-I basal and DHEA-S
      levels and fat mass (FM). To achieve this goal, 10 hypertensive obese subjects
      (HOB-NIFE, 3 males, 7 females, mean age +/- SD 44.6 +/- 1.7 yr; body mass index
      (BMI) 37.1 +/- 2.5 Kg/m2, WHR 0.95 +/- 0.02) received 3-month treatment with
      nifedipine (Adalat Crono 30 Bayer, 1 tab daily) while other 9 hypertensive obese
      (HOB, 3 males, 6 females, 42 +/- 2.4 yr, BMI 35.8 +/- 1.8 Kg/m2, WHR 0.91 +/-
      0.03) were studied during diet only. The same parameters were studied also in 8
      normotensive obese patients (OB: 3 males, 5 females, 48.1 +/- 2.1 yr, BMI 35.8 +/
      2.4 Kg/m2, WHR 0.90 +/- 0.03) on the same balanced hypocaloric diet. Basal
      systolic (SBP) and diastolic (DBP) blood pressure levels in HOB-NIFE and HOB were
      similar. At baseline, all groups had similar basal and OGTT-induced glucose,
      insulin and glucose insulin ratio (GIR) levels as well as IGF-I and DHEA-S
      levels. After 3 months BMI fell to the same extent in all groups (p < 0.05 vs
      baseline) while WHR and FFM/FM ratio did not change. SBP and DBP decreased HOB
      NIFE (p < 0.02) but also during diet alone in both HOB and OB, though to a lesser
      extent (p < 0.05). Both basal and OGTT-stimulated glucose and insulin levels as
      well as IGF-I and DHEA-S levels were not modified in HOB-NIFE as well as in HOB
      and OB. In conclusion, our data indicate that nifedipine treatment does not
      modify glucose tolerance as well as insulin secretion and sensitivity, IGF-I and
      DHEA-S levels in hypertensive abdominal obese patients. Thus, nifedipine
      treatment has no detrimental effects on endocrine-metabolic balance in
      hypertensive obese patients.

PMID- 9633025
TI  - Calcium-dependent low renin syndrome in a diabetic patient with prostaglandin
      deficiency.
AB  - Calcium and prostaglandin are supposed to play a critical role in the renin
      angiotensin aldosterone system. Calcium has been described as an inhibitory
      second messenger for renin exocytosis whereas vasodilatory prostaglandins, such
      as PGE2, are known to stimulate the production of renin. These factors are
      probably interrelated since calcium also enhances urinary prostaglandin release.
      We report the case of a 52 year-old diabetic patient treated with insulin
      injections with intestinal malabsorption leading to chronic hyperkalemia and
      hypocalcemia in whom a low renin syndrome and low levels of urinary
      prostaglandins were observed. The correction of the hypocalcemia was able to
      improve plasma renin as well as urinary prostaglandin levels. This observation
      suggests a prominent role played by calcium on the in vivo regulation of renin
      and prostaglandin release. These results illustrate the closed loop between
      plasma calcium level, urinary prostaglandins production and renin release.

PMID- 9633026
TI  - Angiosarcoma of the thyroid and concurrent hyperthyroidism.
AB  - We describe the exceptional association of an angiosarcoma of the thyroid and
      hyperthyroidism in a 74-year-old woman who presented with a toxic multinodular
      goiter of recent growth. This association reported in two other cases may not be
      fortuitous but due a vascular effect of the angiosarcoma contributing to the
      development of thyrotoxicosis. This case also illustrates the diagnostic
      difficulties and the poor prognosis of this tumor.

PMID- 9633027
TI  - A case of painless thyroiditis possibly triggered by tamoxifen citrate, a
      synthetic antiestrogen.

PMID- 9633028
TI  - Evaluating treatment effectiveness. Changing our expectations.

PMID- 9633029
TI  - Case presentation of a substance-abusing borderline patient. Illustrating use of
      the immediate transactional experience.
AB  - This paper presents a severely disturbed self-mutilating person with a chronic
      substance abuse history. It demonstrates how use of the immediate transactional
      experience is an analytic model, facilitated treatment. The authentic use of the
      therapist's self is endorsed as mutative in facilitating personality change in
      the patient. Fellow professionals are encouraged to respond to this paper in the
      service of fruitful analytic dialogue, in the service of promoting more effective
      treatment of this difficult population in equally difficult times.

PMID- 9633030
TI  - Can syringe exchange serve as a conduit to substance abuse treatment?
AB  - To determine how the city-run New Haven syringe exchange program (SEP) expedited
      requests, for entry into treatment, records of the SEP's drug treatment
      coordinator were analyzed. During the study period, a majority of those
      requesting treatment did not use the SEP to obtain sterile syringes. Comparisons
      between the people requesting treatment and those exchanging syringes revealed
      that those requesting treatment were more likely female and less like White.
      Factors associated with failure to enter treatment included long lag times, worse
      insurance, cocaine use, and requesting primary detoxification only. Majorities of
      the requests, appointments, and entries came from individuals whose treatment was
      to be paid through city welfare. A managed care initiative from the city welfare
      department, which excluded the SEP, halved requests or entries. Subsequent
      addition of the SEP to the initiative did not significantly increase requests or
      entries. Although the SEP initially acted as a conduit to treatment its
      effectiveness was curtailed by the imposition of bureaucratic restrictions.

PMID- 9633031
TI  - The changing role of "using" dreams in addiction recovery.
AB  - The Dream Interview Method of dream interpretation can be applied to dreams
      depicting alcohol and drug use to elucidate the meaning of such dreams in
      relation to stages of recovery. This paper summarizes the method and demonstrates
      its application utilizing seven dreams collected from clients in psychotherapy
      and participants in dream workshops. The incorporation of such interpreted dreams
      into substance abuse treatment as well as their relationship to other life issues
      is discussed.

PMID- 9633032
TI  - Service-level costing of drug abuse treatment.
AB  - This paper presents a methodology for estimating costs of delivering specific
      substance abuse treatment services. Data collected from 13 programs indicate that
      the mean cost of residential treatment is $2,773 per patient per month, and
      outpatient treatment costs average $636 per patient per month. Data are presented
      on the cost patient per month for individual treatment and nontreatment services,
      average number of services, cost per unit of service, and intensity of services.
      In addition to their application to insurance benefit cost estimation, these data
      illustrate the costing of best-practice adolescent treatment consistent with a
      Center of Substance Abuse Treatment (CSAT) Treatment Improvement Protocol. In the
      emerging policy environment, detailed cost estimates like these will aid the
      design of cost-effective treatment programs, and serve the development of the
      substance abuse benefit in a health care reform insurance package.

PMID- 9633033
TI  - Predicting drug treatment entry among treatment-seeking individuals.
AB  - This study examined factors related to drug treatment program entry among 276
      drug abusers seeking treatment referral. Six-month follow-up interviews
      determined that 171 (62.0%) followed through with the treatment referral. The
      analyses indicated that treatment-entry and non-entry subjects did not differ in
      predisposing factors (age, gender, race/ethnicity, education), type of drug use,
      or years of use. A logistic regression analysis indicated that characteristics at
      baseline predicting subsequent treatment entry include legal pressure, lower
      levels of psychological distress and family or social problems, and prior
      successful treatment experience. Legal coercion was an effective factor promoting
      treatment entry. Drug abusers having prior successful treatment experience were
      also more likely to reenter treatment. However, those with more severe problems
      (drug related and others) seemed less likely to enter treatment, indicating that
      psychological distress and family problems may undermine motivation to follow
      through on treatment referral.

PMID- 9633034
TI  - Alcoholics Anonymous affiliation during early recovery.
AB  - This study analyzed the Alcoholics Anonymous (AA) participation of 55 patients
      during the 3 months after their discharge from structured treatment, when dropout
      is high. Three levels of meeting attendance were discerned: low, mid-level, and
      "90 meetings in 90 days." Of greatest interest, the mid-level group showed mixed
      interest in AA practices despite substantial meeting attendance, that is, they
      admitted powerlessness, but had less enthusiasm for the higher power concept, and
      relapsed significantly; they were likely to have a sponsor, but were less
      involved with other AA members; and they reported working the 12 Steps, but were
      less interested in the AA literature. Findings suggest that individuals who are
      attending AA but having difficulty embracing key aspects of the program need
      professional assistance that focuses more on AA practices and tenets and less on
      meeting attendance. Barriers to affiliation can also serve as opportunities for
      furthering both counseling goals and affiliation.

PMID- 9633035
TI  - Organizational issues in conducting tuberculosis screening at a syringe exchange
      program.
AB  - There has been a rise in tuberculosis (TB) cases in the United States and there
      is a potent link between human immunodeficiency virus (HIV) and tuberculosis. In
      New City it is estimated that 40% of the 200,000 injecting drug users are
      infected with HIV. In addition, the tuberculosis case rate is approximately four
      times the national average, and one third of these cases occurred in those
      persons infected with HIV. Drug users have a high prevalence of latent
      tuberculous infection and are at high risk for progression to active
      tuberculosis. Drug users are at high risk for both HIV and TB. Although studies
      have shown the value of incorporating TB services into drug treatment programs,
      the majority of drug users in the United States are not in drug treatment. We
      have been evaluating the feasibility of conducting TB screening and directly
      observed TB preventive therapy for active injecting drug users at a syringe
      exchange program in New York City. This paper describes issues relating to the
      implementation of the TB screening program and discusses general and operational
      issues relevant to integrating medical and public health programs into existing
      programs serving drug using individuals.

PMID- 9633036
TI  - Putting drug use in context. Life-lines of African American women who smoke
      crack.
AB  - The purpose of this exploratory study was to describe a group of African American
      women who smoke crack. Using aggregate data from 208 interviews with women crack
      smokers, we randomly selected 25 women's interview data to create the 25 life
      lines. These life-lines were developed in a similar manner to the time-line
      analysis described by Fullilove and her colleagues (1992); we focused on events
      that are either extraordinarily disturbing (e.g., rape, incest, death of a child,
      etc.), events that are usual but often stressful (e.g., birth of a child, death
      of a parent, etc.), and on periods of drug use. We chose this method of analysis
      so as to highlight the context in which many women come to use crack cocaine. The
      life-lines provided a retrospective (but time-ordered) perspective and in several
      ways provided preliminary support for a stress-diathesis perspective.

PMID- 9633037
TI  - Evaluation of a multisystems model for treating perinatal cocaine addiction.
AB  - Two stages of a gender-specific treatment program for perinatal cocaine-addicted
      women were introduced into a coed peer-led day treatment program and evaluated
      for outcomes. Stage I (N = 21) targeted gender-specific needs, but did not
      expressly promote family reintegration. Stage II (N = 27) augmented the gender
      specific program with a multisystems model for family reintegration. As a control
      for historical effects, nonperinatal clients whose treatment remained the same
      during the periods corresponding to the two stages, were evaluated for outcomes
      (N = 66 for Stage I, N = 75 for Stage II). As hypothesized, urine toxicology and
      retention data were significantly improved for perinatal clients treated in Stage
      II, as compared with those treated in Stage I; no such improvements were noted
      for non-perinatal clients. The data support a conclusion that introducing a
      multisystems framework into a gender-specific program selectively improves
      clinical outcomes for inner-city perinatal cocaine-addicted women.

PMID- 9633038
TI  - A comprehensive pharmacologic-psychosocial treatment program for HIV-seropositive
      cocaine- and opioid-dependent patients. Preliminary findings.
AB  - HIV-seropositive opioid-dependent patients maintained on an opiate-agonist who
      continue to use cocaine and to engage in other high-risk behaviors may benefit
      from enhanced treatment services; however, there is currently little data to
      guide the formulation of such services. We report on a preliminary study in which
      six HIV-seropositive opioid-and cocaine-dependent patients were provided a 12
      week comprehensive pharmacologic/psychosocial treatment program developed
      specifically to meet the treatment needs of HIV-seropositive drug users. This
      program was comprised of buprenorphine (12 mg/day), bupropion (150 mg/day), and
      twice weekly manual-guided group therapy. Results showed significant decreases in
      intravenous cocaine use, cocaine craving, and symptoms of depression. A post-hoc
      comparison to outcomes of eight HIV-seropositive patients receiving standard
      methadone-maintenance found no improvements for patients receiving standard care.
      Controlled investigation of enhanced drug treatment programs for HIV-seropositive
      patients may be warranted.

PMID- 9633039
TI  - Bibliography of literature reviews on drug abuse treatment effectiveness.

PMID- 9633040
TI  - Acute intermittent porphyria: alternative splicing of hydroxymethylbilane
      synthase mRNA excludes exons 3 and 12.
AB  - The hydroxymethylbilane synthase (HMBS) mRNAs from 44 control individuals and 30
      patients suffering from acute intermittent porphyria (AIP), were screened for
      length differences by reverse transcriptase polymerase chain reaction (RT-PCR)
      and any abnormalities were characterized by direct sequencing. Examination of the
      mRNAs extracted from the peripheral blood lymphocytes of the samples revealed
      varying degrees of alternative splicing, involving the removal of exons 3 and 12.
      Approximately 10-50% of the mRNA molecules were affected, despite the absence of
      genomic splice site mutations or any major deviance from consensus splice
      sequence values. The preliminary data obtained from this study suggest that this
      event is a normal occurrence in peripheral blood lymphocytes, and may not be
      associated with the molecular pathology responsible for AIP.

PMID- 9633041
TI  - Specific amplification of Necator americanus or Ancylostoma duodenale DNA by PCR
      using markers in ITS-1 rDNA, and its implications.
AB  - Necator americanus and Ancylostoma duodenale are the two most important species
      of human hookworm, and occur in sympatry over much of their distribution. The
      specific diagnosis of hookworm infections is central to control. Diagnosis
      currently relies on the detection of hookworm eggs in human faeces and/or the
      specific identification of larvae by 'copro-culture' combined with microscopic
      examination. However, the eggs of the two species are morphologically
      indistinguishable, and the procedure of copro-culture is tedious and time
      consuming to carry out. To work toward overcoming these limitations, a molecular
      approach utilizing genetic markers in the first internal transcribed spacer (ITS
      1) of ribosomal DNA (rDNA) was established. The ITS-1 sequences of both hookworm
      species were determined, and specific oligonucleotide primers designed to regions
      of major sequence difference between the species were evaluated in polymerase
      chain reaction (PCR). Using a range of control samples, the primers allowed the
      specific identification of as little as 10 pg DNA of A. duodenale or N.
      americanus. The findings indicate clearly the potential for specific PCR to
      confirm the identity of eggs from faeces and larvae from the environment or host
      tissues. This should have important implications for studying fundamental aspects
      relating to anthelmintic efficacy and the epidemiology of hookworms.

PMID- 9633042
TI  - A simplified sample preparation method from various foods for PCR detection of
      pathogenic Yersinia enterocolitica: a possible model for other food pathogens.
AB  - A simplified method for the direct application of multiplex polymerase chain
      reaction (PCR) was developed to detect plasmid-bearing virulent serotypes of
      Yersinia enterocolitica (YEP+) in a variety of foods. Strains of YEP+
      representing five serotypes were detected in enriched swab samples of
      artificially contaminated pork chops, ground pork, cheese and zucchini using
      multiplex PCR analysis. The method was also effective for identifying YEP+
      strains in naturally contaminated porcine tongues. The use of swabs eliminated
      time-consuming extraction of DNA from food, inhibition of PCR by food-derived
      DNA, interference by background flora and reduced the time needed for processing
      samples. The detection of other food pathogens should be feasible by this
      technique.

PMID- 9633043
TI  - The ftsZ gene as a tool for detection of Mycoplasma fermentans.
AB  - Mycoplasma fermentans was reported as a common contaminant of cell cultures, and
      was shown to either induce or suppress several immunological functions. A strain
      of M. fermentans was recently isolated from a mouse T-lymphoma cell line, which
      differs from other M. fermentans strains by its growth characteristics and was
      designated (in the authors' records) as strain 609. Using the differential
      display technique (DD), a differentially expressed gene that was identified as
      the M. fermentans 609 ftsZ gene was isolated. Comparison of the nucleotide
      sequence of the M. fermentans 609 ftsZ gene to other ftsZ genes showed a 98%
      homology with Mycoplasma fermentans strain K7 and approximately 50% homology with
      Mycoplasma pulmonis and Mycoplasma genitalium. Comparison of the putative amino
      acid sequences of the FtsZ proteins showed similar homology. A polymerase chain
      reaction (PCR) assay to detect the presence of this ftsZ gene was established; it
      is a fast and convenient assay to detect infection of cells by the M. fermentans
      species. This work demonstrates that: (i) DD can be used as a useful technique to
      identify and isolate mycoplasmal genes from infected cells; and (ii) the ftsZ
      gene can be a useful marker to distinguish between different species of
      mycoplasma.

PMID- 9633044
TI  - Rapid and sensitive PCR-based detection and differentiation of aetiologic agents
      of human granulocytotropic and monocytotropic ehrlichiosis.
AB  - The potential of fatal outcome for patients afflicted with human ehrlichioses
      (HME and HGE) necessitates fast and accurate detection of the aetiologic agents
      and timely antibiotic treatment. A polymerase chain reaction (PCR)-based protocol
      is described that can detect as little as 10 copies of ehrlichial 16S rDNA and as
      few as 0.3 HGE-infected neutrophils. The method employs DNAzol for rapid DNA
      extraction from unfractionated whole blood in less than 1 h. For DNA
      amplification, highly specific oligonucleotide primers are designed that
      efficiently detect and distinguish between Ehrlichia chaffeensis and the HGE
      agent. These primers do not prime DNA extracted from closely related ehrlichial
      and rickettsial species. Although total DNA extracted from human blood contains
      nucleic acids that can be non-specifically amplified at moderate to high MgCI2
      concentrations, such non-specific priming of non-ehrlichial DNA can be completely
      eliminated by lowering the MgCI2 concentration to 1 mM. Thus, this PCR-based
      procedure can detect and differentiate HGE and HME with speed, simplicity,
      specificity and sensitivity.

PMID- 9633045
TI  - Differentiation of types 1a, 1b and 2 bovine viral diarrhoea virus (BVDV) by PCR.
AB  - There are two genotypes among bovine viral diarrhoea viruses (BVDV), BVDV1 and
      BVDV2. Within the BVDV1 genotype there are two distinct subgenotypes, BVD1a and
      BVD1b. Serology and monoclonal antibody binding are used to differentiate BVDV
      from classical swine fever virus (CSFV) and border disease virus (BDV), the other
      members of the Pestivirus genus. These techniques are less useful in the
      differentiation and segregation of viruses within the BVDV species. In this
      study, differential polymerase chain reaction (PCR) amplification has been
      evaluated as a tool for segregating BVDV isolates into genotypes and
      subgenotypes. Polymerase chain reaction primers were selected based on the
      comparison of 5' untranslated region sequences from CSVF, BDV, BVDV1a, BVDV1b and
      BVDV2. Differential PCR tests were validated using 345 viruses isolated from
      cattle and small ruminants that had previously been segregated into genotypes and
      subgenotypes. There was 100% correlation between segregation by differential PCR
      and the previous segregation of these viral isolates.

PMID- 9633046
TI  - Spermine-mediated improvement of cycling probe reaction.
AB  - Cycling probe technology (CPT) represents a simple method for detection of DNA
      target sequences. Cycling probe technology utilizes a chimeric DNA-RNA-DNA probe
      which is cleaved by RNase H when hybridized with its complementary target. Probe
      cleavage in the presence or absence of target generates CPT product or
      background, respectively. Addition of non-homologous DNA into the CPT reaction
      affects the background and CPT product. Low amounts of human DNA (4-40 ng) result
      in high background while higher amounts (40-400 ng) inhibit the reaction. The
      simultaneous addition of spermine and EGTA into the CPT reaction containing human
      DNA resulted in a significant release of the inhibition and a reduction of
      background. The presence of spermine alone caused an increase of probe cleavage
      whereas addition of EGTA increased the specificity of the CPT. A possible
      mechanism by which spermine could lead to this improvement of CPT has been
      proposed. Using a membrane-binding assay, the authors demonstrated that human DNA
      competes with the probe for binding to RNase H. Furthermore, by using a DNA
      agarose column, it has been shown that such RNase H-DNA binding can be disrupted
      by spermine. Within the CPT reaction, similar spermine-mediated displacement of
      RNase H from human DNA could lead to an improved CPT efficiency.

PMID- 9633047
TI  - Polymorphisms in the human apolipoprotein aiv gene detected by PCR and
      SSCP/heteroduplex analysis.

PMID- 9633048
TI  - ARMS test for diagnosis of factor V Leiden mutation and allele frequencies in
      France.
AB  - The authors have developed a simple and rapid amplification-refractory mutation
      system (ARMS) assay for the factor V Leiden mutation (MIM 227400.0001).
      Polymerase chain reaction (PCR) primers within exon 10 of the factor V gene were
      designed; one common upstream primer was paired with either a normal or a mutant
      specific downstream primer. The assay was validated using factor V Leiden DNA
      samples of thrombophilic patients ascertained by the restriction enzyme cleavage
      method of reference. In the normal French population, allele frequencies of the
      factor V Leiden mutation are 2.6% for the Parisian region and 1.7% for the south
      of the country.

PMID- 9633049
TI  - [Some problems and some principles of university hospital life].

PMID- 9633050
TI  - [From need-meeting to quality of life].

PMID- 9633051
TI  - [Physiopathology of diabetic nephropathy: what we learn from transplantation].
AB  - The contribution of clinical transplantation to the understanding of the
      pathophysiology of diabetic nephropathy is reviewed. Isolated kidney
      transplantation into diabetic recipients provides the opportunity to observe
      early lesions of recurrence, consisting in mesangium expansion and glomerular
      basement membrane thickening; in these patients, tight glycaemic control can
      significantly slow down the progression of recurrence. Simultaneous kidney
      pancreas transplantation effectively prevents recurrence. Isolated pancreas
      transplantation in the presence of established diabetic nephropathy can prevent
      its progression and seems even able to induce its regression in the long-term
      provided transplantation takes place at an early stage of diabetic nephropathy.
      In summary, clinical transplantation confirms that the quality of glycaemic
      control is the main determinant of both the development and progression of
      diabetic nephropathy. It remains a unique opportunity to study its reversibility.

PMID- 9633052
TI  - [Evaluation of information for renal insufficiency patients before dialysis].
AB  - The aim of this audit was to assess the quality of information given to patients
      before dialysis and to improve the use of this information on the acceptability
      of the treatment. Methods were those used in medical audit: retrospective data
      collection in a sample of patients, comparison to a set of standards given by
      professionals and recommendations disseminated in the group of professionals.
      Results showed that patients received a partial information on the various
      techniques used in dialysis. More complete information is needed. Recommendations
      consisted in a specialised team giving a detailed information on the disease and
      the techniques used in dialysis, with a psychological assistance. After
      implementation of this team, re-assessment showed a consistent benefit of
      structured information and entailed the necessity to improve the process of
      information delivery by general practitioners and specialists.

PMID- 9633053
TI  - [Lupus interstitial cystitis. Apropos of a case].
AB  - We report a case of lupus interstitial cystitis in 17 year-old female. The
      patient presented with suprapubic pain, urinary frequency, dysuria, nocturia and
      no bacterial growth. Intravenous pyelography showed a low capacity bladder with
      thickwall, and a bilateral ureterohydronephrosis. Interstitial cystitis was
      confirmed on bladder biopsy specimen. Clinical symptoms remained eventhough after
      steroid treatment. Clinical signs of cystitis occurring in a patient with
      systemic lupus erythematous could be a manifestation of a lupus cystitis.

PMID- 9633054
TI  - [Tertiary hyperparathyroidism: parathyroid cancer with liver metastases in a
      hemodialyzed patient].
AB  - Parathyroid cancer is very rare in chronic renal failure. Only twelve cases have
      been described, but the actual incidence might be under estimated. Monoclonal
      proliferation have been demonstrated in hyperplasic parathyroid glands of uremic
      patients and the diagnosis between benign or malignant tumor may be difficult.
      Evidence for a deletion of the "Retinoblastoma Tumor Suppressor gene" (RB gene)
      is helpful for the diagnosis of parathyroid cancer, especially in the absence of
      dissemination. A 46-years old male patient on dialysis since 1989 for polycystic
      kidney disease developed a refractory and persistent hyperparathyroidism after
      parathyroidectomy with vascular and osteoarticular complications. Liver nodules
      were localised by sestaultrasonography. MIBI radionucleid scan and were confirmed
      by CT-scan, and ultrasonography. Diagnosis of parathyroid cancer was confirmed by
      the immuno-histochemical study of the biopsied liver nodules and the
      histopathological review of the removed parathyroid glands.

PMID- 9633055
TI  - [Treatment of anemia in chronically dialyzed patients].

PMID- 9633056
TI  - [Letter to the authors of the "Recommendations for clinical practice" concerning
      the prevention of renal osteodystrophy before extra-renal purification].

PMID- 9633057
TI  - Pacing in sick sinus syndrome--need for a prospective, randomized trial comparing
      atrial with dual chamber pacing.

PMID- 9633058
TI  - Interrelations between QRS morphology, duration, and HV interval changes
      following right bundle branch radiofrequency catheter ablation.
AB  - Interrelations between QRS morphology, duration, and HV interval changes in a
      model of "complete" bundle branch block following right bundle branch
      radiofrequency ablation have not been subjected to systematic study. This article
      describes these interrelations in patients who underwent right bundle ablation.
      Over a period of 42 months, 16 patients underwent radiofrequency ablation of the
      right bundle for treatment of bundle branch reentrant tachycardia. All 16
      patients had prolonged HV interval at baseline (minimum = 60 ms; mean = 68 +/- 8
      ms). After ablation, one patient developed complete heart block; the remaining 15
      patients developed complete right bundle branch block (RBBB) and further
      prolongation of the HV interval (increment = 24 +/- 16 ms). In 14 of these 15
      patients, QRS duration was 138 +/- 26 ms before ablation and increased to 168 +/-
      13 ms after ablation. In the remaining patient, the QRS duration was 160 ms
      before ablation and shortened to 144 ms following ablation despite further HV
      prolongation. Larger increases of HV interval after ablation were associated with
      smaller or negative changes in QRS duration (r = -0.77). Three was a direct
      relationship between QRS duration at baseline and the increment in HV interval
      after ablation (r = 0.70), and an inverse relationship between QRS duration
      before and after ablation (r = 0.84). Radiofrequency ablation of right bundle may
      be associated with an increase in HV interval and QRS duration. However, HV
      interval prolongation is not necessarily associated with QRS duration widening. A
      large change in HV interval is more likely to be associated with an already
      prolonged QRS duration before ablation and a lesser increase or even decrease in
      QRS duration after ablation. A shorter QRS duration before ablation is associated
      with a smaller HV interval increase following ablation but a greater increment in
      QRS duration. These findings are consistent with the concept that narrowness of
      QRS duration is due to synchronized activation of ventricular endocardium;
      whereas, QRS duration widening seen with His-Purkinje damage is due to reduced
      synchronization of endocardial activation.

PMID- 9633059
TI  - VDD pacing in persistent left superior vena cava.
AB  - Although persistent left superior vena cava (PLSVC) is the most common major
      venous anomaly of the heart, associated absence of the right superior vena cava
      with normal visceral situs is exceedingly rare. Such a patient presented with
      complete heart block requiring permanent pacing. This was achieved successful
      using a single lead VDD system via the PLSVC with atrial sensing in the coronary
      sinus.

PMID- 9633060
TI  - Long-term thrombosis after transvenous permanent pacemaker implantation.
AB  - To assess the efficacy of prophylactic administration of anticoagulant and
      antiaggregant drugs to prevent venous thrombosis after long-term transvenous
      permanent pacemaker implantation, venograms were performed in 100 consecutive
      patients at the elective replacement of the pacemaker. Mean follow-up period
      after initial transvenous permanent pacemaker implantation was 6.0 years. The
      venograms demonstrated normal in 77 patients. The remaining 23 venograms showed
      venous stenosis in 11 patients and total obstruction in 12 patients. Twenty-one
      of these 23 patients had venous collateral circulation. No difference was found
      in the incidence of venous abnormalities according to the route of entry, the
      lead insulation, the total number of the implanted leads, and anticoagulant and
      antiaggregant drugs. All these patients have remained asymptomatic. In
      conclusion, the incidence of venous thrombosis after long-term transvenous pacing
      is 23% and the causes of venous thrombosis may be endothelial trauma and
      underlying venous stenosis. As this article describes a retrospective limited
      study, we cannot find the efficacy of prophylactic administration of
      anticoagulant and antiaggregant drugs to prevent venous thrombosis formation
      after transvenous permanent pacemaker implantation. Further prospective study
      will be needed to assess the efficacy of prophylactic administration of
      anticoagulant and antiaggregant drugs.

PMID- 9633061
TI  - Narrow complex tachycardia with VA block: diagnostic and therapeutic
      implications.
AB  - To review our experience with cases of narrow complex tachycardia with VA block,
      highlighting the difficulties in the differential diagnosis, and the therapeutic
      implications. Prior reports of patients with narrow complex tachycardia with VA
      block consist of isolated case reports. The differential diagnosis of this
      disorder includes: automatic junctional tachycardia, AV nodal reentry with final
      upper common pathway block, concealed nodofascicular (ventricular) pathway, and
      intra-Hissian reentry. Between June 1994 and January 1996, six patients with
      narrow complex tachycardia with episodes of ventriculoatrial block were referred
      for evaluation. All six patients underwent attempted radiofrequency ablation of
      the putative arrhythmic site. Three of six patients had evidence suggestive of a
      nodofascicular tract. Intermittent antegrade conduction over a left-sided
      nodofascicular tract was present in two patients and the diagnosis of a concealed
      nodofascicular was made in the third patient after ruling out other tachycardia
      mechanisms. Two patients had automatic junctional tachycardia, and one patient
      had atrioventricular nodal reentry with proximal common pathway block. Attempted
      ablation in the posterior and mid-septum was unsuccessful in patients with
      nodofascicular tachycardia. In contrast, those with atrioventricular nodal
      reentry and automatic junctional tachycardia readily responded to ablation. The
      presence of a nodofascicular tachycardia should be suspected if: (1) intermittent
      antegrade preexcitation is recorded, (2) the tachycardia can be initiated with a
      single atrial premature producing two ventricular complexes, and (3) a single
      ventricular extrastimulus initiates SVT without a retrograde His deflection. The
      presence of a nodofascicular pathway is common in patients with narrow complex
      tachycardia and VA block. Unlike AV nodal reentry and automatic junctional
      tachycardia, the response to ablation is poor.

PMID- 9633062
TI  - Psychosocial outcome after ICD implantation: a current perspective.
AB  - Depression and reduced sexual functioning have been identified as problems
      following ICD placement. We examined these issues, and multiple other quality-of
      life measures, and their relationship to ICD and ICD discharge. Patients were 64
      +/- 11 years old, 72% male, and had undergone ICD 20 +/- 14 months previously.
      Fifty-eight patients responded to a confidential biopsychosocial questionnaire.
      Positive attitudes toward the procedure increased from 52% before to 76% after
      implantation. Satisfaction correlated most strongly with less anger (P = 0.002, r
      = 0.45), less worry about ICD size (P = 0.007, r = 0.38), less sadness (P = 0.01,
      r = 0.37), and perceived better health (P = 0.01, r = 0.35). Of these ICD
      patients, 20%-58% reported measures of depression, and sexual frequency was
      reduced in 45%. Despite successful ICD placement, health concern increased in 62%
      of the respondents. Thirty-nine percent attended support groups; 96% found them
      very helpful. Mean number of ICD discharges described by responders was 5 +/- 11.
      Fifty percent of our sample reported > or = 1 shock; equal numbers had 1, 2-5, 6
      10, and more than 10 shocks. Sixty-two percent of men had at least one discharge
      compared to 13% of women. After controlling for cardiac clinical variables,
      experiencing > or = 1 ICD shock was strongly associated with anxiety about family
      (odds ratio = 7.3), reduced new activities (odds ratio = 6.9), increased sadness
      (odds ratio = 6.2), and health worry (odds ratio = 5.8). Experiencing > or = 5
      ICD shocks was strongly associated with increased health concern (odds ratio =
      13.6), increased sadness (odds ratio = 12.5), increased fatigue (odds ratio =
      6.1), current sadness (odds ratio = 5.8), and increased nervousness (odds ratio =
      5.3). ICD implantation powerfully affects quality-of-life. Postimplantation
      health concern is paradoxically increased despite improvement in actual health.
      Negative emotions are associated with defibrillator discharge.

PMID- 9633063
TI  - Effects of respiration phase on ventricular defibrillation threshold in a hot can
      electrode system.
AB  - The impedance of defibrillation pathways is an important determinant of
      ventricular defibrillation efficacy. The hypothesis in this study was that the
      respiration phase (end-inspiration versus end-expiration) may alter impedance
      and/or defibrillation efficacy in a "hot can" electrode system. Defibrillation
      threshold (DFT) parameters were evaluated at end-expiration and at end
      inspiration phases in random order by a biphasic waveform in ten anesthetized
      pigs (body weight: 19.1 +/- 2.4 kg; heart weight: 97 +/- 10 g). Pigs were
      intubated with a cuffed endotracheal tube and ventilated through a Drager SAV
      respirator with tidal volume of 400-500 mL. A transvenous defibrillation lead (6
      cm long, 6.5 Fr) was inserted into the right ventricular apex. A titanium can
      electrode (92-cm2 surface area) was placed in the left pectoral area. The right
      ventricular lead was the anode for the first phase and the cathode for the second
      phase. The DFT was determined by a "down-up down-up" protocol. Statistical
      analysis was performed with a Wilcoxon matched pair test. The median impedance at
      DFT for expiration and inspiration phases were 37.8 +/- 3.1 omega, and 39.3 +/-
      3.6 omega, respectively (P = 0.02). The stored energy at DFT for expiration and
      inspiration phases were 5.7 +/- 1.9 J and 6.0 +/- 1.0 J, respectively (P =
      0.594). Shocks delivered at end-inspiration exhibited a statistically significant
      increase in electrode impedance in a " hot can" electrode system. The finding
      that DFT energy was not significantly different at both respiration phases
      indicates that respiration phase does not significantly affect defibrillation
      energy requirements.

PMID- 9633064
TI  - Inappropriate sensing of atrial stimuli in patients with third-generation
      defibrillators and DDD pacemakers.
AB  - Although the problem of ICD sensing of paced ventricular stimuli has been
      resolved by incorporation of VVI pacing into current ICDs, many patients required
      separate DDD pacemakers. We report a problematic PM-ICD interaction: the
      inability to prevent sensing of paced atrial stimuli ("atrial sensing") leading
      to double-counting in DDD-PM-requiring patients with transvenous (TV) ICDs with
      aggressive autogain sensing (CPI Ventak PRxII or III). Four of eight patients
      receiving both transvenous DDD PMs and ICDs (CPI Endotak lead, at the RV apex),
      had atrial sensing, leading to double counting, despite intraoperative testing of
      multiple atrial locations with an active fixation lead. Five patients had a
      PRxII/III ICD, four with atrial sensing (80%), and three a PRx without atrial
      sensing. Patients with atrial sensing were not distinguished by any clinical or
      device related variable. In patients with atrial sensing (all with heart block),
      the PM was programmed to VDD mode. No patient has received inappropriate therapy
      or failed to sense VF in follow-up. In many patients with TV ICDs who required
      DDD pacing, no atrial position can be found without ICD sensing of atrial
      stimuli. While in patients with heart block this problem can be circumvented by
      programming to the VDD mode, in patients with sinus incompetence it may only be
      resolved by the combination ICD-DDD PM, currently in development.

PMID- 9633065
TI  - Different trends of changes in heart rate variability in patients with anterior
      and inferior acute myocardial infarction.
AB  - Modifications in heart rate variability (HRV) parameters occur after acute
      myocardial infarction. The aim of this study was to evaluate the trend of HRV
      change during the acute phase and the first month after myocardial infarction,
      and establish whether they were affected by the anterior or inferior location of
      the infarction. The time-domain HRV measures of 59 patients with a first
      uncomplicated acute myocardial infarction were computed from 24-hour ECG
      recordings made on days 1, 2, 10, and 28 after hospital admission. At day 1, the
      mean RR cycle length (NN), the standard deviation of the NN intervals (SDNN), and
      the root mean square successive difference of NN intervals (RMSSD) were lower in
      the patients with anterior myocardial infarction. Although the parameters were
      similar in all of the patients at day 28, their behavior over time was different
      (P = 0.01): the SDNN in the patients with inferior myocardial infarction had
      decreased to the values found in anterior myocardial infarction patients by day 2
      but, at day 10, both NN and SDNN tended to recover in both groups; RMSSD had
      diminished in both groups by day 2, but at day 10, had increased in the patients
      with anterior, but not in those with inferior myocardial infarction. These
      findings suggest that (1) in the very early phase of myocardial infarction, HRV
      is different in the two locations, (2) during the first hours of myocardial
      infarction patients with inferior location showed a greater vagal activity than
      patients with anterior location that became lower at day 10, and (3) the recovery
      of HRV is an early phenomenon in both groups, being already evident by the second
      week after myocardial infarction.

PMID- 9633066
TI  - A fractally coated, 1.3 mm2 high impedance pacing electrode.
AB  - Minimizing the geometric surface area of pacing electrodes increases impedance
      and reduces the current drain during stimulation, provided that voltage (pulse
      width) thresholds remain unchanged. This may be feasible by coating the electrode
      surface to increase the capacity of the electrode tissue interface and to
      diminish polarization. Ten unipolar, tined leads with a surface area of 1.3 mm2
      and a "fractal" coating of iridium (Biotronik SD-V137) were implanted in the
      ventricle, and electrogram amplitude (unfiltered), slew-rate, pacing threshold
      (0.5 ms), and impedance (2.5 V; 0.5 ms) were measured by the 5311 PSA
      (Medtronic). On days 0. 2. 5. 10, 28, 90, 180, 360 postimplant, sensing threshold
      (up to 7.0 mV, measuring range 1-14 mV on day 360 only) and the strength duration
      curve (0.5-4.0 V; 0.03-1.5 ms; steps: 0.5 V; 0.01 ms, respectively) were
      determined, the minimum charge delivered per pulse (charge threshold), and the
      impedance were taken from pacemaker telemetry (Intermedics 294-03). Data were
      compared with those of an earlier series of 20 unipolar, tined TIR-leads
      (Biotronik) with a surface area of 10 mm2 and a @actal" coating of titanium
      nitride. With the model SD-V137 versus TIR, intraoperative electrogram amplitudes
      were 15.1 +/- 6.1 versus 14.4 +/- 3.9 mV (NS), slew rates 3.45 +/- 1.57 versus
      1.94 +/- 1.06 V/s (P < 0.05), pacing thresholds 0.16 +/- 0.05 versus 0.52 +/-
      0.15 V (P < 0.01) and impedance measurements 1,136 +/- 175 versus 441 +/- 73
      omega (P < 0.0001), respectively. During follow-up, sensing thresholds were the
      same with both leads. Differences in pulse width thresholds lost its significance
      on day 28 but resumed on day 360 (SD-V137; 0.08 +/- 0.04 ms; TIR: 0.16 +/- 0.06
      ms at 2.5 V; P < 0.01). With an electrode surface of 1.3 mm2, charge per pulse
      and impedance consistently differed from control, being 0.15 +/- versus 0.66 +/-
      0.20 microC (P < 0.001) and 1,344 +/- 376 versus 538 +/- 79 omega respectively,
      one year after implantation (P < 0.0001). In summary, "fractally" coated small
      surface electrodes do not compromise sensing; by more than doubling impedance
      against controls they offer pacing thresholds (mainly in terms of charge) that
      are significantly lower than with the reference electrode.

PMID- 9633067
TI  - Postshock recovery interval of relatively refractory myocardium as a possible
      explanation for disparate defibrillation efficacy between monophasic and biphasic
      waveforms.
AB  - We investigated the electrophysiological background for the waveform related
      variability of defibrillation efficacy. In 22 open-chest dogs, a localized
      potential gradient was created using an 8-V or 16-V field stimulus across a pair
      of plate electrodes separated by 5 mm. The post shock recovery interval of the
      nondepolarized myocardium adjacent to the excited area was estimated by the
      residual refractory period after an appropriately timed field stimulus. The
      postshock recovery interval and the defibrillation threshold were compared among
      six different waveforms but with the same total duration of 12 ms (n = 11) or 16
      ms (n = 11). Six defibrillation thresholds in individual hearts showed a
      significant inverse correlation with postshock recovery intervals in most dogs
      (8/11) tested with a total pulse duration of 12 ms (8 V stimulus: r = -0.80 +/-
      0.20 [n = 11]). In contrast, waveforms with a total duration of 16 ms failed to
      reveal this distinct relationship. We conclude that the waveform related
      variability of defibrillation efficacy is associated with the refractoriness of
      relatively refractory myocardium when the total pulse duration is within a
      certain range. However, the mechanisms responsible for waveform performance may
      vary as the total pulse duration changes.

PMID- 9633068
TI  - Variable effects of adenosine on retrograde conduction in patients with
      atrioventricular nodal reentry tachycardia.
AB  - Adenosine has been demonstrated to reliably produce transient block of
      atrioventricular nodal (AVN) conduction, and has been advocated as a method of
      differentiating retrograde conduction via the atrioventricular node from
      accessory pathway conduction. However, the response of retrograde AVN to
      adenosine in patients with typical atrioventricular nodal reentry tachycardia
      (AVNRT) remains unclear. We evaluated 13 patients (mean age 45 +/- 20 years) with
      typical AVNRT prior to AVN modification. During right ventricular pacing, a rapid
      bolus of adenosine (0.2 mg/kg; maximum 18 mg) was administered. Adenosine
      sensitivity, defined by transient ventriculoatrial block, was observed in six
      patients, while in seven patients ventriculoatrial conduction was unaffected. An
      adenosine bolus administered during sinus rhythm or atrial pacing resulted in
      antegrade atrioventricular block in all the adenosine resistant patients in whom
      this was performed (n = 6). Comparisons of AVN electrophysiological
      characteristics between the adenosine sensitive and adenosine resistant patients
      were performed. There was no difference with respect to ventriculoatrial
      effective refractory period, ventriculoatrial Wenckebach, AVNRT cycle length, and
      His to atrial echo interval in AVNRT. However, there was a trend toward a longer
      antegrade fast pathway ERP in the adenosine sensitive group (P = 0.07).
      Electrophysiological properties do not predict retrograde AVN adenosine
      sensitivity. Adenosine does not cause retrograde AVN block in all patients with
      AVNRT, and therefore cannot reliably distinguish between retrograde conduction
      via the AVN or an accessory pathway.

PMID- 9633069
TI  - Atrial fibrillation and anticoagulation in patients with permanent pacemakers:
      implications for stroke prevention.
AB  - Several large prospective randomized trials have demonstrated that
      anticoagulation with warfarin reduces the risk of thromboembolic stroke in high
      risk patients with chronic AF by approximately 70%. Large numbers of patients
      with permanent pacemakers have AF, and anticoagulation rates in this population
      have not been described. In a prospective analysis of 110 consecutive patients
      attending the pacemaker clinic of a large university hospital we assessed the
      number of patients with AF and the proportion of these patients who were
      receiving anticoagulation to prevent thromboembolic stroke. Where necessary,
      temporary pacemaker reprogramming to low ventricular rates was utilized to
      facilitate the diagnosis of AF. Fifty-three of the 110 patients (48%) were
      diagnosed with AF, all of whom (100%) had accepted high risk factors for
      thromboembolic stroke. Only eight of the 53 (15%) had been anticoagulated with
      warfarin. Thirty-six of the 53 patients (68%) diagnosed with AF had no prior
      documented diagnosis of chronic AF, and the majority had no symptoms suggesting
      AF. A single lead II ECG was insufficient in 67 of the 110 patients (61%) to
      diagnose the underlying atrial rhythm; the remainder required 12-lead ECGs or
      temporary pacemaker reprogramming to low ventricular rates to diagnose the
      underlying atrial rhythm. AF is common in patients with permanent pacemakers. It
      is commonly asymptomatic, and anticoagulation is markedly underutilized in
      reducing stroke risk in these patients. Attention to the possibility of AF in
      paced patients should allow prompt diagnosis and allow both the initiation of
      anticoagulation in order to reduce thromboembolic stroke risk and consideration
      for cardioversion of AF to sinus rhythm.

PMID- 9633070
TI  - Electroanatomical mapping of the heart: basic concepts and implications for the
      treatment of cardiac arrhythmias.
AB  - The CARTO electroanatomical mapping system represents a paradigm shift in the
      ability to map the three-dimensional anatomy of the heart and determine the
      cardiac electrical activity at any given mapped point. The system associates
      anatomical structure and electrophysiological data and displays the combined
      information in an easily readable, visual fashion. The system consists of a
      roving mapping catheter with small magnetic sensors in the tip, a fixed sensor
      that acts as a reference point, a low magnetic field generating pad, and a data
      acquisition and display system. When the roving catheter is moved in three
      dimensional space, its location in relation to the fixed sensor is monitored by
      the system, with a resolution of < 1 mm. By gating the acquisition of points in
      space to the cardiac electrical activity, points that represent both location and
      electrical activity at that location can be acquired and displayed on a computer
      screen. After acquiring a number of points, a three-dimensional representation is
      constructed, and may be displayed from any viewing projection. Clinical
      applications of the system include defining the mechanisms of arrhythmias,
      designing ablation strategies, guiding ablations, and improving the safety of
      mapping and ablation procedures by allowing localization of critical cardiac
      structures such as the atrioventricular node and His bundle. The system holds the
      potential to both further our understanding of arrhythmias and increase the
      safety, efficacy, and efficiency of catheter ablation.

PMID- 9633072
TI  - Implantable defibrillator diagnostic storage capabilities: evolution, current
      status, and future utilization.
AB  - There has been a rapid and significant evolution in the stored diagnostic
      information available from implantable cardioverter defibrillators (ICDs). The
      diagnostic information available in current generation ICDs has greatly enhanced
      the clinicians' ability to determine the rhythm triggering device therapy as well
      as to identify potential problems with the ICD system. Furthermore, this
      information may be useful in identifying triggers of ventricular arrhythmias in
      patients at high risk for sudden death. The history, evolution, value, and
      limitations of the stored diagnostic capabilities of implantable defibrillators
      are discussed.

PMID- 9633073
TI  - Effect of atrioventricular sequential pacing on left ventricular flow dynamics in
      a patient with mid-ventricular obstruction.
AB  - The effect of dual chamber atrioventricular sequential pacing on the
      intraventricular pressure gradient was tested using Doppler echocardiography in a
      patient with hypertrophic mid-ventricular obstruction. Atrioventricular
      sequential pacing with relatively short atrioventricular delays reduced in the
      left ventricular pressure gradient at the mid-ventricular level. Also,
      atrioventricular sequential pacing affected the degree and profile of the
      isovolumetric relaxation flow. These results suggest that atrioventricular
      sequential pacing affects both systolic and diastolic left ventricular flow
      dynamics in mid-ventricular obstruction.

PMID- 9633071
TI  - Use of a three-dimensional, nonfluoroscopic mapping system for catheter ablation
      of typical atrial flutter.
AB  - Recent studies have shown that typical atrial flutter (AFL) results from right
      atrial reentry around the tricuspid annulus (TA), constrained between the TA and
      crista terminalis (CT) on the free-wall and the TA and eustachian ridge (ER) on
      the septum. Creation of a complete line of conduction block across the
      subeustachian isthmus, between the TA and ER, eliminates AFL. The accuracy of
      fluoroscopy in localizing the anatomical boundaries and previous radiofrequency
      application sites is limited. This article describes an approach for utilizing a
      new three-dimensional nonfluoroscopic electroanatomical mapping system (CARTO) to
      examine the global right atrial activation pattern in patients during AFL,
      localize the anatomical boundaries, and create a complete line of conduction
      block by ablation across the subeustachian isthmus. During AFL, the locations of
      CT and ER are identified by double atrial potentials recorded along the
      intercaval region and between the inferior vena cava and coronary sinus ostium,
      respectively. Radiofrequency ablation across the subeustachian isthmus is
      performed during coronary sinus pacing. Beginning at TA, the ablation electrode
      is moved toward ER in 2-3 mm increments. Each movement is marked on the right
      atrial map to visualize the ablation line. In the event of residual conduction
      across the ablation line, defects in the ablation line are located by mapping
      along the previous ablation sites guided by CARTO system to locate the transition
      from the double atrial potentials (indicating block) to a single atrial potential
      (indicating conduction). Radiofrequency ablation to the site showing the single
      atrial potential along the ablation line produces complete conduction block
      across the subeustachian isthmus. In conclusion, the new electroanatomical
      mapping system allows precise 3-D localization of the anatomical boundaries of
      the AFL reentrant circuit, and facilitates ablation by accurately locating
      defects in the ablation line.

PMID- 9633074
TI  - Paroxysmal atrial flutter suppressed by repair of a large paraesophageal hernia.

PMID- 9633075
TI  - Entrapment of an ablation catheter in the cardiac venous system: a case report.
AB  - Cannulation of the coronary sinus is a common procedure with infrequent
      complications. We report an unusual case of a steerable "dumb-bell" catheter
      passed through the ostium of the coronary sinus prior to an intended
      radiofrequency ablation procedure becoming stuck and requiring general anesthesia
      for extraction. We caution against the use of such catheters with a "waist" for
      the cannulation of the coronary sinus.

PMID- 9633076
TI  - Alternative locations for internal defibrillator electrodes.
AB  - Successful defibrillation is described in two patients in whom the defibrillating
      electrode was positioned in the coronary sinus and right ventricular outflow
      tract as alternative sites. Internal cardiac defibrillation has been successful
      with single or multiple endocardial electrodes, epicardial patch electrodes, and
      subcutaneous surface electrodes (patch, array) in varying combinations and
      recently with an active can electrode. While the traditional location of the
      endocardial electrode has been the right ventricular apex, we describe two
      patients in whom defibrillation was successful in alternate locations, the
      coronary sinus and the right ventricular outflow tract.

PMID- 9633077
TI  - Left ventricular malposition of a transvenous cardioverter defibrillator lead: a
      3-year follow-up.
AB  - A case of left ventricular malposition of a transvenous implantable cardioverter
      defibrillator lead through an atrial septal defect is presented. The patient has
      been continually anticoagulated with warfarin. A 3-year follow-up has thus far
      been uneventful.

PMID- 9633078
TI  - Successful slow pathway ablation in a patient with atrioventricular nodal
      reentrant tachycardia having a proximal common pathway.
AB  - Radiofrequency catheter ablation was attempted in a patient with atrioventricular
      nodal reentrant tachycardia (AVNRT). AVNRT was easily inducible but an
      intermittent loss of the atrial activation was observed during AVNRT suggesting
      the presence of a proximal common pathway. During sinus rhythm, a relatively
      delayed activation that was compatible with a slow potential, was recorded
      anterior to the ostium of coronary sinus, and radiofrequency catheter ablation
      application (20 watts) to the site induced junction tachycardia. After an
      additional radiofrequency catheter ablation application to close the site, AVNRT
      became noninducible without deterioration of atrioventricular conduction through
      a fast pathway. This is the first case in which radiofrequency catheter ablation
      application to the slow potential recording site has been successful, even in
      AVNRT having a proximal common pathway.

PMID- 9633079
TI  - Carotid sinus massage as a diagnostic and therapeutic tool for atrial flutter
      fibrillation.
AB  - Alterations in vagal tone can influence the atrial fibrillatory process by
      changing the atrial refractory period. We observed in a patient with paroxysmal
      atrial fibrillation (AF) that carotid sinus massage (CSM) changed a "coarse" type
      of fibrillation into a "fine" type, followed by termination of the arrhythmia.
      Although coincidental conversion of AF into sinus rhythm could not be excluded,
      we concluded that it is worth while to try CSM in every patient presenting with
      AF prior to other interventions to restore sinus rhythm.

PMID- 9633080
TI  - Impedance rise, only clue to severe insulation damage in a transvenous single
      lead AICD-system.
AB  - We report a case of severe insulation damage 10 months after implantation of a
      fourth-generation single-lead implantable cardioverter defibrillator in a 45-year
      old patient with dilative cardiomyopathy. The measured impedance was > 2000 Ohm
      and decreased to < 100 Ohm after slight pressure was applied to the device. All
      other parameters including intracardiac ECGs and markers were normal. Despite
      this delicate finding operative exploration revealed severe insulation damage of
      the pace-sense arm of the plug and insulation loss proximal to the distal coil of
      the lead.

PMID- 9633081
TI  - Aborted implantable cardioverter defibrillator shock during facial
      electrosurgery.
AB  - A patient with a fourth-generation transvenous implantable cardioverter
      defibrillator system nearly received an inappropriate defibrillation discharge
      while undergoing electrofulguration of keratotic facial skin lesions. The
      incident was confirmed by analyses of the implantable cardioverter
      defibrillator's time/date stamped event log and stored electrogram record.
      Therapy was withheld by the noncommitted implantable cardioverter-defibrillator
      as the pulsed electrocautery was not continued beyond the charging period.

PMID- 9633082
TI  - Coronary artery dissection complicating radiofrequency catheter ablation via the
      retrograde approach.

PMID- 9633083
TI  - Multiple inappropriate shocks precipitated by interrogation of an implantable
      cardioverter defibrillator.
AB  - A 57-year-old man suffered multiple inappropriate shocks from an implantable
      cardioverter defibrillator that could not be inactivated because the magnet
      switch feature was deactivated. Attempts to interrogate the defibrillator caused
      shocks to be delivered. Emergent explantation was performed and a loose sensing
      lead was discovered. Sensing and defibrillation leads functioned normally, and
      testing of the explanted generator demonstrated no abnormalities. A new generator
      was put in place and the patient has been without shocks for 6 months. This case
      illustrates the need for robust methods of attenuating electromagnetic
      interference and the importance of multiple methods of device inactivation.

PMID- 9633084
TI  - Recipient to donor conduction of atrial tachycardia following orthotopic heart
      transplantation.
AB  - We report a case of atrial tachycardia in a 60-year-old male 8 years
      postorthotopic heart transplantation. At electrophysiology study, the clinical
      rhythm was found to arise from the remnant of the recipient atrium and was
      successfully terminated by delivery of radiofrequency energy. Surgical scars
      formed at the anastomosis of the recipient and donor atrium during the time of
      orthotopic heart transplantation are thought to electrically isolate the two
      areas. Although rarely recognized, dysrhythmias originating from the recipient
      atrial remnant may occur more often than previously thought.

PMID- 9633085
TI  - Rapid ventricular pacing in a pacemaker patient undergoing magnetic resonance
      imaging.
AB  - Magnetic resonance imaging (MRI) generates potent electromagnetic forces in the
      form of a static, gradient, or pulsed radiofrequency magnetic field that can
      result in pacemaker malfunction. This report documents a case of rapid cardiac
      pacing during MRI in a patient with a dual chamber pacemaker. Although the
      mechanism of rapid cardiac pacing is unclear, it was directly related to
      radiofrequency pulsing. We postulated that the lead acts as an antenna for
      radiofrequency energy that interacts with the pacemaker's output circuit, thus,
      causing cardiac pacing at a cycle length representing a multiple of the
      repetition time; or perhaps rapid pacing is related to induced currents generated
      between the MRI unit and the pacing lead.

PMID- 9633086
TI  - Determination of Giardia cyst viability in environmental and faecal samples by
      immunofluorescence, fluorogenic dye staining and differential interference
      contrast microscopy.
AB  - Amongst the techniques suggested for the determination of Giardia cyst viability,
      the use of the fluorogenic dyes, fluorescein diacetate (FDA) and propidium iodide
      (PI) is the most often recommended, even though it appears to overestimate the
      number of viable cysts. In the present study, the replacement of FDA with 4',6
      diamidino-2-phenylindole (DAPI) allowed simultaneous direct immunofluorescence
      with monoclonal antibody labelled with fluorescein isothiocyanate (MAb-FITC).
      Under these conditions, it was possible both to quantify the cysts according to
      the immunofluorescence technique, and to appreciate their viability by using
      fluorogenic dye staining (DAPI and PI) and differential interference contrast
      (DIC) microscopy. This method proved to be significantly better than the counting
      methods normally suggested. The technique has been applied to Giardia cysts
      recovered from faeces and wastewater sludge.

PMID- 9633087
TI  - Large plasmids in ruminal strains of Selenomonas ruminantium.
AB  - The plasmid content of six different isolates of Selenomonas ruminantium from the
      rumen of sheep, cows or goats was examined by electron microscopy. In addition to
      small plasmids (< 12 kb) studied previously, all six strains contained at least
      one plasmid larger than 20 kb. Plasmid sizes of 1.4, 2.1, 2.4, 5.0, 6.2, 20.4,
      20.8, 22.7, 23.3, 29.3, 30.7, 34.4 and 42.6 kb were estimated from contour length
      measurements. DNA-DNA hybridization experiments revealed homology among the large
      plasmids from five strains, while the 20.8 kb plasmid from a sixth isolate showed
      no apparent relationship with the plasmids of the other strains.

PMID- 9633088
TI  - A method for the selective enumeration and isolation of ruminal Lactobacillus and
      Streptococcus.
AB  - Ruminal lactic acid-producing bacteria were selectively isolated and enumerated
      using a one hour aerobic exposure prior to incubation on a semi-selective
      Lactobacillus medium, MRS, under anaerobic conditions. The technique allowed
      growth of pure cultures of ruminal Lactobacillus spp. and Streptococcus bovis
      without supporting the growth of pure cultures of any of the prominent ruminal
      bacterial species. In mixed cultures, the one hour aerobic pre-incubation
      inhibited the growth of the obligate anaerobic ruminal bacteria which can
      otherwise grow on the MRS medium, and the subsequent anaerobic incubation
      permitted maximal recovery of the weakly aerotolerant ruminal lactic acid
      producing Lactobacillus spp. and Streptococcus spp. The efficacy of this
      technique in selecting exclusively for the lactic acid-producing bacteria was
      also demonstrated from populations of rumen bacteria from mixed culture end-point
      in vitro fermentation, continuous in vitro culture and isolations from fresh
      ruminal samples.

PMID- 9633089
TI  - Antimicrobial resistance of bacteria isolated from slaughtered and retail
      chickens in South Africa.
AB  - Animal feed is increasingly being supplemented with antibiotics to decrease the
      risk of epidemics in animal husbandry. This practice could lead to the selection
      for antibiotic resistant micro-organisms. The aim of this study was to determine
      the level of antibiotic resistant bacteria present on retail and abattoir
      chicken. Staphylococci, Enterobacteriaceae, Salmonella and isolates from total
      aerobic plate count were tested for resistance to vancomycin, streptomycin,
      methicillin, tetracycline and gentamicin using the disc diffusion susceptibility
      test; resistance to penicillin was determined using oxacillin. Results from the
      antibiotic code profile indicated that many of the bacterial strains were
      displaying multiple antibiotic resistance (MAR). A larger proportion of
      resistance to most antibiotics, except for vancomycin, was displayed by the
      abattoir samples, therefore suggesting that the incidence of MAR pathogenic
      bacteria was also higher in the abattoir samples. This resistance spectrum of
      abattoir samples is a result of farmers adding low doses of antibiotics to
      livestock feed to improve feeding efficiency so that the animals need less food
      to reach marketable weight. The lower incidence of MAR pathogenic bacteria in the
      retail samples is a result of resistance genes being lost due to lack of
      selective pressure, or to the fact that the resistant flora are being replaced by
      more sensitive flora during processing. The use of subtherapeutic levels of
      antibiotics for prophylaxis and as growth promoters remains a concern as the laws
      of evolution dictate that microbes will eventually develop resistance to
      practically any antibiotic. Selective pressure exerted by widespread
      antimicrobial use is therefore the driving force in the development of antibiotic
      resistance. This study indicated that a large proportion of the bacterial flora
      on fresh chicken is resistant to a variety of antibiotics, and that resultant
      food-related infections will be more difficult to treat.

PMID- 9633090
TI  - The oxidative stress response in Enterococcus faecalis: relationship between H2O2
      tolerance and H2O2 stress proteins.
AB  - The hydrogen peroxide (H2O2) stress response in Enterococcus faecalis ATCC19433
      was investigated. A 2.4 mmol l-1 H2O2 pretreatment conferred protection against a
      lethal concentration (45 mmol l-1) of this agent. The relatively high
      concentrations of H2O2 used for adaptation and challenge treatments in Ent.
      faecalis emphasised the strong resistance towards oxidative stress in this
      species. Various stresses (NaCl, heat, ethanol, acidity and alkalinity) induced
      weak or strong H2O2 cross-protection. This paper describes the involvement of
      protein synthesis in the active response to lethal dose of H2O2, in addition to
      the impressive enhancement of synthesis of five H2O2 stress proteins. Combined
      results suggest that these proteins might play an important role in the H2O2
      tolerance response.

PMID- 9633091
TI  - Segregational and structural instability of recombinant plasmid carrying genes
      for naphthalene degrading pathway.
AB  - The stability of recombinant plasmid carrying genes for naphthalene
      mineralization was determined. A strain of Pseudomonas putida capable of
      mineralizing naphthalene (Nap+) via salicylate (Sal+) was isolated, and all
      regulatory and structural genes for the whole pathway were found to be encoded on
      a 25 kb EcoRI fragment of an approximately 83 kb plasmid present in this strain.
      The 25 kb EcoRI fragment was cloned into a tetracycline-resistant (TcR) cloning
      vector pLAFR3 and the recombinant plasmid, pRKJ3 (Nap+, Sal+, TcR), thus obtained
      was transferred into the plasmid-free strain Pseudomonas putida KT2442 in order
      to test the stability of the plasmid. Plasmid pRKJ3 was found to be
      segregationally and/or structurally unstable, depending on the growth conditions.
      Two types of novel derivative strains having the phenotypes Nap-, Sal+, TcR and
      Nap-, Sal-, TcR with specific deletions of approximately 2 kb and 18 kb,
      respectively, were obtained.

PMID- 9633092
TI  - Biogenic amine production by wild lactococcal and leuconostoc strains.
AB  - Two qualitative and one quantitative HPLC methods were evaluated for the
      detection of biogenic amine producers among wild dairy lactococcal and
      leuconostoc strains. High tyramine producers ranging from 370 to 807 mg l-1 were
      detected by qualitative methods and confirmed by HPLC analysis. Tyramine levels
      detected throughout the incubation time depended on the concentration of the
      amino acid precursor available and no tyramine production was observed when
      strains were grown in milk. However, increasing amounts of tyramine were detected
      in cultures grown in milk supplemented with different concentrations of tyrosine.
      Qualitative methods failed to detect weak producers so that tryptamine production
      (< 7 mg l-1) could only be determined by HPLC. None of the tested strains was
      able to produce histamine. Simultaneous production of different amines was
      observed by HPLC although no colour change was observed in the specific
      decarboxylase media. Thus, it was concluded that the amine forming ability should
      be taken into account when selecting starters for milk fermentations. Qualitative
      methods could be used as a first screening step to eliminate the highest amine
      producers while the quantitative methods would detect any producing strain.

PMID- 9633093
TI  - The production of D-acetoin by a transgenic Escherichia coli.
AB  - A 6 kbp SphI fragment encoding genes for the enzymes alpha-acetolactate synthase
      (ALS), alpha-acetolactate decarboxylase (ALDC) and meso-2,3-butanediol
      dehydrogenase (meso-BDH), involved in the formation of meso-2,3-butanediol (meso
      BD) from pyruvic acid, was cloned into plasmid pUC118. When derivatives of this
      plasmid were introduced into Escherichia coli JM109, the transformants were able
      to produce D-acetoin (D-AC) without contamination with L-acetoin (L-AC).

PMID- 9633094
TI  - Density of lectin-like receptors in the FLO1 phenotype of Saccharomyces
      cerevisiae.
AB  - An improved lectin assay was recently developed to determine the density of
      lectin sites present on the surface of a haploid strain 1209 of Saccharomyces
      cerevisiae exhibiting the Flo1 phenotype. The assay is based on the use of FITC
      avidin which contains a mannose side chain which functions as a binding site to
      the cell wall lectins termed zymolectins. An examination of the effect of culture
      time on the zymolectin density indicated no significant effect (P > 0.05)
      confirming other findings that Flo1 acts in a constitutive manner. Zymolectin
      densities for this strain averaged 5.4 x 10(6) sites cell-1.

PMID- 9633095
TI  - Disinfectant testing: use of the Bioscreen Microbiological Growth Analyser for
      laboratory biocide screening.
AB  - A new method is described for screening potential biocides based on the
      traditional suspension test using the Bioscreen optical plate reader. This new
      method is rapid, reproducible, quantitative and cost effective. Data obtained by
      this new method are not directly equivalent to the log reduction normally quoted,
      but give a measurement of the total effect of the biocide on the microbe
      population, measuring the effect of injury as well as death (non-viability). The
      method allows for the routine examination of disinfection kinetics, the study of
      which leads to greater scientific insight into disinfection than that achieved by
      the standard 5 min, one-point, disinfection tests currently employed.

PMID- 9633096
TI  - Using specific polyclonal antibodies to study the malolactic enzyme from
      Leuconostoc oenos and other lactic acid bacteria.
AB  - Specific polyclonal antibodies directed against the malolactic enzyme of
      Leuconostoc oenos were obtained. Despite the homologies between the malolactic
      enzymes from Leuc. oenos and Lactococcus lactis, no immunological relationship
      was detected with the L. lactis malolactic enzyme, suggesting differences in
      their structural organization. The use of the antiserum also demonstrated that
      the problem of heterologous expression occurring in the recombinant Escherichia
      coli strain (Labarre et al. 1996a) resulted in a low synthesis of the malolactic
      enzyme from Leuc. oenos. Moreover, a small amount of the protein was found to be
      peripherally associated to the membrane of Leuc. oenos.

PMID- 9633097
TI  - Detection and characterization of a bacteriocin produced by Lactococcus lactis
      subsp. cremoris R isolated from radish.
AB  - Bacteria isolated from radish were identified as Lactococcus lactis subsp.
      cremoris R and their bacteriocin was designated lactococcin R. Lactococcin R was
      sensitive to some proteolytic enzymes (proteinase-K, pronase-E, proteases,
      pepsin, alpha-chymotrypsin) but was resistant to trypsin, papain, catalase,
      lysozyme and lipase, organic solvents, or heating at 90 degrees C for 15, 30 and
      60 min, or 121 degrees C for 15 min. Lactococcin R remained active after storage
      at -20 and -70 degrees C for 3 months and after exposure to a pH of 2-9. The
      molecular weight of lactococcin R was about 2.5 kDa. Lactococcin R was active
      against many food-borne pathogenic and food spoilage bacteria such as
      Clostridium, Staphylococcus, Listeria, Bacillus, Micrococcus, Enterococcus,
      Lactobacillus, Leuconostoc, Streptococcus and Pediococcus spp., but was not
      active against any Gram-negative bacteria. Lactococcin R was produced during log
      phase and reached a maximum activity (1600 AU ml-1) at early stationary phase.
      The highest lactococcin R production was obtained in MRS broth with 0.5% glucose,
      at 6.5-7.0 initial pH values, 30 degrees C temperature and 18-24-h incubation
      times. Lactococcin R adsorbed maximally to its heat-killed producing cells at pH
      6-7 (95%). Crude lactococcin R at 1280 AU ml-1 was bactericidal, reducing colony
      counts of Listeria monocytogenes by 99.98% in 3 h. Lactococcin R should be useful
      as a biopreservative to prevent growth of food-borne pathogenic and food spoilage
      bacteria in ready-to-eat, dairy, meat, poultry and other food products.
      Lactococcin R differs from nisin in having a lower molecular weight, 2.5 kDa vs
      3.4 kDa, and in being sensitive to pepsin and alpha-chymotrypsin to which nisin
      is resistant.

PMID- 9633098
TI  - Alkaline phosphatase release assay to determine cytotoxicity for Listeria
      species.
AB  - A simple cytotoxicity assay for Listeria species was developed by assaying
      alkaline phosphatase (AP) release from an infected hybrid B lymphocyte (Ped-2E9)
      line. Eight of eight L. monocytogenes and six of 11 L. ivanovii strains induced
      significantly high AP release from Ped-2E9 cells compared to five other L.
      ivanovii strains and other Listeria spp. In contrast, all L. monocytogenes and L.
      ivanovii test strains showed high release of lactate dehydrogenase (LDH) activity
      from Ped-2E9 cells. The molecular mass of AP was estimated to be about 128-165
      kDa, suggesting severe membrane damage in Ped-2E9 cells due to Listeria
      infection. The data presented here indicate that AP assay could be used over LDH
      assay to detect Listeria-induced cell cytotoxicity.

PMID- 9633099
TI  - Factors affecting the heat resistance of Escherichia coli O157:H7.
AB  - Escherichia coli O157:H7 has been reported as being not particularly heat
      resistant. However, several factors which might increase its heat resistance have
      been investigated in this study using five strains. Increase in growth
      temperature to 40 degrees C, as found in the cow gut, heat-shock at sub-lethal
      temperatures of 42, 45, 48 and 50 degrees C, and variable heating rate (1 degree
      C min-1 to 23 degrees C min-1) had no dramatic effect on heat resistance. Growth
      phase had a marked impact on heat resistance; late stationary phase cells were
      more heat-resistant than were log phase cells. The difference in heat resistance
      between the two phases of growth became more pronounced when cells were
      resuspended in fresh nutrient broth; heat resistance of late stationary phase
      cells increased dramatically whereas no such effect was observed with log phase
      cells. The addition of polyphosphates to the heating medium did not increase heat
      resistance. A reduction in water activity of the heating medium from 0.995 to
      levels between 0.980 and 0.960 also resulted in a marked increase in heat
      resistance. This effect was more pronounced under conditions of extremely low
      water activity created by resuspending late stationary phase cells in sunflower
      oil. Survivors were detected even after a heat treatment at 60 degrees C for 1 h
      or 70 degrees C for 5 min. It can be confirmed that this serotype has no unusual
      heat resistance and that the heating environment markedly affects resistance.

PMID- 9633101
TI  - Single paternity of clutches and sperm storage in the promiscuous green turtle
      (Chelonia mydas).
AB  - Paternity of 22 green turtle (Chelonia mydas) clutches from 13 females of the
      southern Great Barrier Reef breeding population was determined through
      microsatellite analyses at five loci, including the analysis of successive
      clutches for nine of the females. A large number of alleles per locus (10-40)
      provided probabilities of detecting multiple paternity that were quite high,
      particularly at all loci combined (99.9%). Although green turtles are promiscuous
      breeders and there was an expectation of finding extensive multiple paternity,
      only two clutches were multiply sired and, in these, very few eggs had been
      fertilized by a secondary male. The rarity of multiple paternity may reflect
      either a low proportion of multiple matings by females in this population, or
      sperm competition, possibly resulting from a first-male sperm preference.
      Additionally, the analysis of > 900 offspring provided data on mutations, which
      included 20 mutation events that were observed in 27 offspring and involved both
      maternal and paternal lineages. Most mutations (n = 16) occurred at a single
      highly variable locus and their presence emphasizes the need to use multiple loci
      in paternity studies.

PMID- 9633100
TI  - Invasion genetics of the Mediterranean fruit fly: variation in multiple nuclear
      introns.
AB  - Biological invasions generally start from low initial population sizes, leading
      to reduced genetic variation in nuclear and especially mitochondrial DNA.
      Consequently, genetic approaches for the study of invasion history and population
      structure are difficult. An extreme example is the Mediterranean fruit fly,
      Ceratitis capitata (Medfly), for which successive invasions during this century
      have resulted in a loss of 60% of ancestral genetic variation in isozymes and 75%
      of variation in mitochondrial DNA. Using Medflies as an example, we present a new
      approach to invasion genetics that measures DNA sequence variation within introns
      from multiple nuclear loci. These loci are so variable that even relatively
      recently founded Medfly populations within California and Hawaii retain ample
      genetic diversity. Invading populations have only lost 35% of the ancestral
      genetic variation. Intron variation will allow high-resolution genetic
      characterization of invading populations in both natural and managed systems,
      although non-equilibrium methods of analysis may be necessary if the genetic
      diversity represents sorting ancestral polymorphism.

PMID- 9633102
TI  - Population genetic structure of North Atlantic, Mediterranean Sea and Sea of
      Cortez fin whales, Balaenoptera physalus (Linnaeus 1758): analysis of
      mitochondrial and nuclear loci.
AB  - Samples were collected from 407 fin whales, Balaenoptera physalus, at four North
      Atlantic and one Mediterranean Sea summer feeding area as well as the Sea of
      Cortez in the Pacific Ocean. For each sample, the sex, the sequence of the first
      288 nucleotides of the mitochondrial (mt) control region and the genotype at six
      microsatellite loci were determined. A significant degree of divergence was
      detected at all nuclear and mt loci between North Atlantic/Mediterranean Sea and
      the Sea of Cortez. However, the divergence time estimated from the mt sequences
      was substantially lower than the time elapsed since the rise of the Panama
      Isthmus, suggesting occasional gene flow between the North Pacific and North
      Atlantic ocean after the separation of the two oceans. Within the North Atlantic
      and Mediterranean Sea, significant levels of heterogeneity were observed in the
      mtDNA between the Mediterranean Sea, the eastern (Spain) and the western (the
      Gulf of Maine and the Gulf of St Lawrence) North Atlantic. Samples collected off
      West Greenland and Iceland could not be unequivocally assigned to either of the
      two areas. The homogeneity tests performed using the nuclear data revealed
      significant levels of divergence only between the Mediterranean Sea and the Gulf
      of St Lawrence or West Greenland. In conclusion, our results suggest the
      existence of several recently diverged populations in the North Atlantic and
      Mediterranean Sea, possibly with some limited gene flow between adjacent
      populations, a population structure which is consistent with earlier population
      models proposed by Kellogg, Ingebrigtsen, and Sergeant.

PMID- 9633103
TI  - The postfire discomycete Geopyxis carbonaria (Ascomycota) is a biotrophic root
      associate with Norway spruce (Picea abies) in nature.
AB  - The hypothesis that the postfire discomycete Geopyxis carbonaria (Ascomycota,
      Pezizales, Pyronemataceae) has a biotrophic association with roots of Norway
      spruce (Picea abies) in nature was tested by isolation of fungal strains from
      fresh, brown, smooth mycorrhiza-like root tips of Norway spruce collected from
      below the depth of detrimental heat penetration in a postfire site. The
      morphology of seven culture isolates originating from the smooth mycorrhiza-like
      root tips of two different spruce trees was congruent with the morphology of
      axenic culture isolates obtained from ascospores of G. carbonaria. DNA sequences
      of the nuclear ribosomal internal transcribed spacers ITS1 and ITS2 from these
      root-derived cultures and the ascosporic G. carbonaria culture isolates were
      found to be identical, further supporting the conclusion that the isolates were
      conspecific. The extensive ascocarp and ascospore formation of G. carbonaria
      which succeeds a forest fire may be explained in terms of a fungal escape from a
      moribund tree associate. Possible ecological adaptations of G. carbonaria to the
      pre- and postfire community are discussed.

PMID- 9633104
TI  - Male mating success in an aquatically mating pinniped, the harbour seal (Phoca
      vitulina), assessed by microsatellite DNA markers.
AB  - Similar to many other pinniped species, harbour seals (Phoca vitulina) mate
      exclusively at sea. Here we present the first attempt to measure male mating
      success in an aquatically mating pinniped. Male mating success was estimated by
      paternity analysis in two cohorts of pups born at Sable Island, Nova Scotia,
      Canada, using microsatellite DNA markers. The genotypes of 275 pups born in 1994
      and 1995 were compared to those of 90 candidate males at six microsatellite loci
      using a likelihood approach to resolve paternity. Paternity could be assigned for
      two, 22, 40 and 85 pups at confidence levels of 95, 80, 65 and 50%, respectively.
      Most successful males were assigned the paternity of a single offspring,
      suggesting a low variance in male mating success relative to most pinniped
      species. The proportion of paternal half sibs within cohorts and between
      maternally related sibs estimated by maximum likelihood were not significantly
      different from zero. It is thus unlikely that most offspring were sired by a
      small number of highly successful unsampled males, and that female harbour seals
      do not usually exhibit fidelity to the same male in sequential breeding seasons.
      A low level of polygyny in Sable Island harbour seals is consistent with
      predictions based on their breeding ecology, as females are highly mobile and
      widely dispersed in the aquatic mating environment at Sable Island.

PMID- 9633105
TI  - Statistical confidence for likelihood-based paternity inference in natural
      populations.
AB  - Paternity inference using highly polymorphic codominant markers is becoming
      common in the study of natural populations. However, multiple males are often
      found to be genetically compatible with each offspring tested, even when the
      probability of excluding an unrelated male is high. While various methods exist
      for evaluating the likelihood of paternity of each nonexcluded male, interpreting
      these likelihoods has hitherto been difficult, and no method takes account of the
      incomplete sampling and error-prone genetic data typical of large-scale studies
      of natural systems. We derive likelihood ratios for paternity inference with
      codominant markers taking account of typing error, and define a statistic delta
      for resolving paternity. Using allele frequencies from the study population in
      question, a simulation program generates criteria for delta that permit
      assignment of paternity to the most likely male with a known level of statistical
      confidence. The simulation takes account of the number of candidate males, the
      proportion of males that are sampled and gaps and errors in genetic data. We
      explore the potentially confounding effect of relatives and show that the method
      is robust to their presence under commonly encountered conditions. The method is
      demonstrated using genetic data from the intensively studied red deer (Cervus
      elaphus) population on the island of Rum, Scotland. The Windows-based computer
      program, CERVUS, described in this study is available from the authors. CERVUS
      can be used to calculate allele frequencies, run simulations and perform
      parentage analysis using data from all types of codominant markers.

PMID- 9633106
TI  - Characterization of microsatellite loci in a New World primate, the mantled
      howler monkey (Alouatta palliata).

PMID- 9633107
TI  - Sequence tagged microsatellite site (STMS) markers in the Musaceae.

PMID- 9633108
TI  - Isolation and characterization of microsatellite loci in the anther smut fungus
      Microbotryum violaceum.

PMID- 9633109
TI  - Chance and risk of controlling rabies in large-scale and long-term immunized fox
      populations.
AB  - The large-scale immunization of European fox populations against rabies is
      currently under the microscope for reducing the considerable expenditure without
      putting public health at risk. Empirical knowledge is inadequate to interpret the
      lasting sporadic incidences and, therefore, to verify the final success of the
      immunization campaigns. By using a proven simulation model we show that rabies
      can persist on a very low level in the form of spatio-temporal moving infection
      clusters within a highly immunized fox population. We found further: (i) the
      existence of a threshold after which the chance of eradicating the disease by
      vaccination increases clearly, and (ii) that at least six years of 70% mean
      immunization rate are required to guarantee a likely success.

PMID- 9633110
TI  - Mapping the ranges and relative abundance of the two principal African malaria
      vectors, Anopheles gambiae sensu stricto and An. arabiensis, using climate data.
AB  - Members of the Anopheles gambiae complex are major malaria vectors in Africa. We
      tested the hypothesis that the range and relative abundance of the two major
      vectors in the complex, An. gambiae sensu stricto and An. arabiensis, could be
      defined by climate. Climate was characterized at mosquito survey sites by
      extracting data for each location from climate surfaces using a Geographical
      Information System. Annual precipitation, together with annual and wet season
      temperature, defined the ranges of both vectors and were used to map suitable
      climate zones. Using data from West Africa, we found that where the species were
      sympatric, An. gambiae s.s. predominated in saturated environments, and An.
      arabiensis was more common in sites subject to desiccation (r2 = 0.875, p <
      0.001). We used the nonlinear equation that best described this relationship to
      map habitat suitability across Africa. This simple model predicted accurately the
      relative abundance of both vectors in Tanzania (rs = 0.745, p = 0.002), where
      species composition is highly variable. The combined maps of species' range and
      relative abundance showed very good agreement with published maps. This technique
      represents a new approach to mapping the distribution of malaria vectors over
      large areas and may facilitate species-specific vector control activities.

PMID- 9633111
TI  - Herd immunity to filarial infection is a function of vector biting rate.
AB  - Despite the existence of an impressive body of work on human immune responses
      against filarial infections, the occurrence of a protective response to infection
      remains unclear. Here, we use a combined modelling and comparative data analysis
      framework to address this issue for human infections with the filarial parasite,
      Wuchereria bancrofti. By analogy with previous work, the analysis involves the
      comparison of observed field patterns of infection with epidemiological patterns
      predicted by a mathematical model of parasite immunity. Unlike most other human
      helminths, which are transmitted by ingestion or dermal penetration, exposure to
      infection with lymphatic filariasis can be measured explicitly in terms of vector
      mosquito biting rates, thereby also allowing, probably for the first time,
      examination of the suggested role of exposure in generating herd immunity to
      macroparasites. Observed field patterns in this study were derived from 19
      different published studies, which gave parallel estimates of community exposure
      rates and the corresponding age--prevalence patterns of infection, while
      predictions of the epidemiological impact of herd immunity were obtained using a
      catalytic model framework. The results provide the first conclusive evidence to
      date that variations in the observed age--prevalence patterns of infection in
      filariasis can be effectively explained by the occurrence of an exposure-driven
      acquisition of herd immunity. We discuss this result in terms of implications for
      the new World Health Organization-led initiative for the global control of this
      parasitic disease.

PMID- 9633112
TI  - Switch in rod opsin gene expression in the European eel, Anguilla anguilla (L.).
AB  - The rod photoreceptors of the European eel, Anguilla anguilla (L.), alter their
      wavelength of maximum sensitivity (lambda max) from c.a. 523 nm to c.a. 482 nm at
      maturation, a switch involving the synthesis of a new visual pigment protein
      (opsin) that is inserted into the outer segments of existing rods. We
      artificially induced the switch in rod opsin production by the administration of
      hormones, and monitored the switch at the level of mRNA accumulation using
      radiolabelled oligonuleotides that hybridized differently to the two forms of eel
      rod opsin. The production of the deep-sea form of rod opsin was detected 6 h
      after the first hormone injection, and the switch in rod opsin expression was
      complete within four weeks, at which time only the mRNA for the deep-sea opsin
      was detectable in the retinal cells. It is suggested that this system could be
      used as a tractable model for studying the regulatory control of opsin gene
      expression.

PMID- 9633113
TI  - Gap junctions with amacrine cells provide a feedback pathway for ganglion cells
      within the retina.
AB  - In primates, one type of retinal ganglion cell, the parasol cell, makes gap
      junctions with amacrine cells, the inhibitory, local circuit neurons. To study
      the effects of these gap junctions, we developed a linear, mathematical model of
      the retinal circuitry providing input to parasol cells. Electrophysiological
      studies have indicated that gap junctions do not enlarge the receptive field
      centres of parasol cells, but our results suggest that they make other
      contributions to their light responses. According to our model, the coupled
      amacrine cells enhance the responses of parasol cells to luminance contrast by
      disinhibition. We also show how a mixed chemical and electrical synapse between
      two sets of amacrine cells presynaptic to the parasol cells might make the
      responses of parasol cells more transient and, therefore, more sensitive to
      motion. Finally, we show how coupling via amacrine cells can synchronize the
      firing of parasol cells. An action potential in a model parasol cell can excite
      neighbouring parasol cells, but only when the coupled amacrine cells also fire
      action potentials. Passive conduction was ineffective due to low-pass temporal
      filtering. Inhibition from the axons of the coupled amacrine cells also produced
      oscillations that might synchronize the firing of more distant ganglion cells.

PMID- 9633114
TI  - Menstrual cycle variation in women's preferences for the scent of symmetrical
      men.
AB  - Evidence suggests that female sexual preferences change across the menstrual
      cycle. Women's extra-pair copulations tend to occur in their most fertile period,
      whereas their intra-pair copulations tend to be more evenly spread out across the
      cycle. This pattern is consistent with women preferentially seeking men who
      evidence phenotypic markers of genetic benefits just before and during ovulation.
      This study examined whether women's olfactory preferences for men's scent would
      tend to favour the scent of more symmetrical men, most notably during the women's
      fertile period. College women sniffed and rated the attractiveness of the scent
      of 41 T-shirts worn over a period of two nights by different men. Results
      indicated that normally cycling (non-pill using) women near the peak fertility of
      their cycle tended to prefer the scent of shirts worn by symmetrical men.
      Normally ovulating women at low fertility within their cycle, and women using a
      contraceptive pill, showed no significant preference for either symmetrical or
      asymmetrical men's scent. A separate analysis revealed that, within the set of
      normally cycling women, individual women's preference for symmetry correlated
      with their probability of conception, given the actuarial value associated with
      the day of the cycle they reported at the time they smelled the shirts. Potential
      sexual selection processes and proximate mechanisms accounting for these findings
      are discussed.

PMID- 9633115
TI  - Identification of catecholamines in the immune system by electrospray ionization
      mass spectrometry.
AB  - The first evidence that catecholamines might be present in the immune system was
      provided by capillary electrophoresis combined with electrochemical detection.
      Here, we present the first structural characterization of the endogenous
      catecholamines isolated from human peripheral blood mononuclear cells. Dopamine,
      L-DOPA and norepinephrine were detected and were identified with electrospray
      ionization mass spectrometry by determination of the protonated molecular species
      of each catecholamine and their major fragments generated in the electrospray
      source with a nozzle-skimmer voltage method. This technique, in conjunction with
      accurate mass measurement, allowed us to identify in an unfractionated sample the
      content of catecholamines in extracted cells in a quantitative manner, with
      structure-specific methodology. The data unambiguously confirm our previous
      tentative findings, and also strengthen the importance of the regulatory function
      of catecholamines in the immune system and the existence of an autocrine loop,
      where lymphocytes may down-regulate their own activity.

PMID- 9633116
TI  - Combination of nozzle-skimmer fragmentation and partial acid hydrolysis in
      electrospray ionization time-of-flight mass spectrometry of synthetic peptides.
AB  - For reliable confirmation of peptide structures, nozzle-skimmer collisionally
      induced dissociation was found in many cases to be insufficient, and partial acid
      hydrolysis was employed as a complementary technique. The utility of combining
      these fragmentation methods is demonstrated in two examples where the complete
      sequences of two synthetic peptides (peptide I, MW 2290 and peptide II, MW 1482)
      were unambiguously determined. In a third example, three different valine
      deletions in a 2 kDa synthetic peptide were identified and their positions
      unambiguously established. A home-built electrospray ionization time-of-flight
      mass spectrometer with orthogonal extraction was used for these analyses. The
      performance of this instrument with a resolving power of up to 7500, a mass
      accuracy of < or = 10 ppm, and a detection limit of 1 fmol was shown to be well
      suited for such studies. As a substitution to conventional external calibration,
      a more convenient and equally accurate internal 3-point calibration is proposed,
      based on the low mass ions that are present in almost all peptide spectra.

PMID- 9633117
TI  - Characterization of the phosphorylation of rat tyrosine hydroxylase using
      electrospray mass spectrometry.

PMID- 9633118
TI  - [Aponeurotic suspension of a vesico-urethral anastomosis after radical
      prostatectomy].
AB  - In order to try to enhance postoperative continence rates after radical
      retropubic prostatectomy, a fascial sling suspension was performed at the time of
      the operation in 75 patients (group 2). Postoperative continence was compared to
      that of the 63 previous patients (group 1). Complete continence rate were 43 of
      75 (57%) in group 2 and 17 of 63 (27%) in group 1 (p = 0.0003) at 1 month, 57 of
      75 (76%) in group 2 and 36 of 63 (57%) in group 1 (p = 0.0149) at 3 months, 65 of
      75 (87%) in group 2 and 46 of 63 (73%) in group 1 at 6 months, 69 of 75 (92%) in
      group 2 and 50 of 63 (79%) in group 1 at 9 months, and 72 of 75 (96%) in group 2
      and 51 of 63 (81%) in group 1 at 12 months. Fascial sling suspension resulted in
      an earlier return and more complete recovery of urinary continence in men
      undergoing radical prostatectomy.

PMID- 9633119
TI  - [Radical prostatectomy: presentation of 2 varying technics for control of the
      venous plexus and the implementation of a vesico-urethral anastomosis].
AB  - Even if the first radical prostatectomy was performed more than ninety years ago
      by Hugh Hampton Young, it's only during the 20 last years that an anatomical
      approach to this technique has been developed, to reduce the number of
      complications routinely described. The evolution of the procedure allow us how to
      make the operation safer, to perform it in a bloodless field and increase the
      possibility to preserve continence and potency. We would like to show you how two
      simple technical variations for the control of dorsal vein complex and the vesico
      uretral anastomosis can, at our opinion, decrease the number of operative and
      postoperative complications. A retrospective review was performed on 168 clinical
      localised prostate cancer patient (stages T1 to T2 N0 M0) treated in our hospital
      between December 1987 and March 1998. All these patients underwent retropubic
      radical prostatectomy with pelvic lymphadenectomy. The preoperative clinical
      stage was T1 for 48.2% and T2 for 51.8%. The mean age of the patients at
      operation was 64.4 years and the mean PSA level at diagnosis was 12.4 ng/ml. Our
      results revealed that 97% of the patients are now perfectly continent and that
      the continence was immediately recovered by 16% at the removal of the bladder
      catheter.

PMID- 9633120
TI  - The place and the results of monotherapy.

PMID- 9633121
TI  - [The question of intermittent hormonal treatment of cancer of the prostate].

PMID- 9633122
TI  - Quality of life through therapeutic advances. Pharmaceutical company news: Ipsen
      N.V.
AB  - IPSEN is the Belgian subsidiary of the independent European pharmaceutical
      company Beaufour Ipsen, founded in 1929 by Dr. Henri Beaufour. With an expanding
      international presence, the group invests almost 20% of group turnover in
      research and development of high technology ethical products. Beaufour Ipsen R &
      D's fundamental goal is quality of life for patients with a special emphasis on
      homeostatic regulation, achieving the optimal efficacy versus tolerance ratio.

PMID- 9633123
TI  - Urodynamics in children: what and how to do it?

PMID- 9633124
TI  - Urodynamic and electrophysiological testing in pediatric neurourology.
AB  - In our institution, children with voiding disorders are submitted to a detailed
      evaluation comprising a careful clinical examination, laboratory tests, imaging
      (kidney ultrasonography and voiding cystourethrography) and urodynamic tests.
      Depending on the etiology of voiding dysfunction, children are subjected to a non
      invasive or an invasive urodynamic evaluation. Non invasive urodynamic testing
      comprises a free urinary flowmetry associated or not with an EMG recording of the
      pelvic floor. Invasive urodynamic testing consists of a pressure-flow study or a
      video-XR-urodynamic test. In rare instances, genitourinary electrophysiological
      investigations will be performed. Herein we describe these different urodynamic
      and electrophysiologic tests.

PMID- 9633125
TI  - Bladder augmentation and substitution in the female patient.

PMID- 9633126
TI  - Surgery or renal cancer--is lymphadenectomy useful?

PMID- 9633127
TI  - Is adrenalectomy part of radical nephrectomy?
AB  - Standard radical nephrectomy entails en bloc removal of the kidney together with
      Gerota's fascia and the ipsilateral adrenal. Thanks to the refinement of imaging
      techniques (ultrasound, CT and MRI), smaller tumors are being diagnosed. In
      addition, direct extension to the adrenal gland or adrenal metastasis can be
      detected in most cases. This is why several authors reserve adrenalectomy for
      large and/or upper pole tumors or abnormal appearing glands on preoperative CT
      scan. However, preoperative diagnosis is not always accurate. Furthermore,
      micrometastatic adrenal invasion at the time of nephrectomy and late recurrences
      in the persistent adrenal have been documented, so that partisans of
      adrenalectomy only spare the adrenal in exceptional cases. The authors have
      reviewed several series in the litterature as well as there own, and conclude
      that ipsilateral adrenalectomy can be omitted for small middle- or lower pole
      tumors when the adrenal appears normal on CT and during the surgical
      intervention.

PMID- 9633128
TI  - [An argument for partial nephrectomy in small non-fatty masses of the kidney].

PMID- 9633129
TI  - A plea for radical nephrectomy.

PMID- 9633130
TI  - Reconstruction of the urethra after pelvic trauma.

PMID- 9633131
TI  - Controversies in management of urethral trauma after pelvic fracture in men.
AB  - Whenever trauma of the urethra is suspected a "test" catheterisation is
      potentially bad and useless. Retrograde urethrography should be performed before
      use of any catheter. Doctors in urgency department should be trained to do this.
      Suprapubic diversion under imaging guidance is the best solution when trauma is
      diagnosed. In complete rupture without extreme displacement of both ends of the
      urethra, reconstruction is foreseen at day 7 to 10 after trauma. Bleeding is
      stopped at that moment and elasticity of the tissues is still sufficient. A
      second urethrogram the day before intervention is advocated for better judgement
      of the lesions. Endoscopy with a flexible endoscope from above is performed as
      the first step of the operation. Minor distances or incomplete lesions of the
      urethra can be coped with endoscopic realignment. Distances of more than 1 cm are
      treated by open perineal route only leaving the pelvic hematoma closed. This
      technique should be restricted to referee centers in view of the small numbers of
      cases.

PMID- 9633132
TI  - Early endoscopic realignment for complete traumatic rupture of the posterior
      urethra--21 patients.

PMID- 9633133
TI  - [CONSORT: an attempt to improve the quality of publication of clinical trials].

PMID- 9633134
TI  - [Prescription habits in a primary health care district: approach to an indication
      prescription study].
AB  - OBJECTIVE: To analyse the profile of medical prescription and prescription habits
      in the most common illnesses in a Primary Health Care district. DESIGN:
      Descriptive crossover study. SETTING: Algeciras-La Linea (Cadiz) Primary Care
      district. MEASUREMENTS AND MAIN RESULTS: A randomised sample of clinical
      histories stratified by months was selected. This included 338 Paediatrics cases
      (< 8 years old) and 665 general medical cases (> 8). The therapeutic groups most
      commonly prescribed for the children were R (45.7%) and J (27.1%) The therapeutic
      groups most used among the > 8 group were C (17.9%), R (14.8%), N (14.7%) and A
      (14.3%). Hypertension was the most common chronic pathology in this group (8.9%),
      treated most often by ACEIs (44.9%). CONCLUSIONS: 1) In our ambit, the most
      widespread pathology signified the greatest consumption of therapeutic groups. 2)
      The indication-prescription analysis detected prescription habits that need to be
      watched: the use of antibiotics and expectorants/mucolytics in ARI and the use of
      fixed-dose combinations which are hard to justify. Prescription habits in
      Hypertension treatment and Hyperlipidaemia also merit a consensus analysis.

PMID- 9633135
TI  - [Health information in the daily local press].
AB  - OBJECTIVE: To know how much health-related information is published in the daily
      local press, type of information; pathologies; practical help offered, and
      sources. DESIGN: Crossover descriptive study. SETTING: Community. PARTICIPANTS:
      Health articles (events and publicity excluded) published in the newspapers of
      Bizkaia: Deia, Egin, Egunkaria, El Correo and El Mundo; sample included all
      issues from one fortnight of June and one fortnight of September of 1996.
      MEASUREMENTS AND MAIN RESULTS: 501 articles, which occupied 1.57% of the
      impressed surface, were published. 90% of the issues had health articles. 19.8%
      appeared in once-weekly health sections. Subjects considered as health culture
      were 49.9% scientific and technical information and 9.8% health habits and
      vaccinations. When compared with the rest of the newspaper, health sections gave
      more explicit advice (p = 0.04) and diferred in sources of information (p <
      0.01). CONCLUSIONS: Health articles are almost daily published. The most frequent
      type was the spread of scientific and technical information. Current information
      topics are dominant. A few articles give explicit advice or referred to health
      habits. Acknowledgement of the sources could be improved. It would be desirable
      to investigate the quality of contents.

PMID- 9633136
TI  - [Homeopathic and primary care doctors: how they see each other and how they see
      their patients: results of a qualitative investigation].
AB  - OBJECTIVE: To explore the views of Primary Care and homeopathic doctors in the
      same geographical and population catchment area towards Homeopathy as a
      discipline and the motives that bring patients to use its services. DESIGN: A
      qualitative study, using in-depth interviews and a focus group. SETTING: A
      community of 18,000 inhabitants with a Health Centre and four homeopathic
      physicians. PARTICIPANTS: The four homeopathic physicians and nine of the ten
      doctors from the Health Centre. METHOD: After face-to-face and later telephone
      interviews, each of the four homeopathic physicians was interviewed in depth and
      the author led a focus group with the 9 Health Centre doctors. MAIN RESULTS: a)
      From the homeopaths: they emphasised an integrated patient-centred approach. They
      insisted on their status as doctors and that their treatment was not iatrogenic,
      etc. b) From PC doctors: They were ignorant of Homeopathy. They identified it
      with a type of remedy of which they knew nothing, but for which they demanded
      scientific evidence, etc. CONCLUSIONS: PC doctors' ignorance of Homeopathy put
      them at risk of not understanding patients' expectations. It seems that the
      patient-centred, as against disease-centred, care model is, in practice, outside
      the scope of PC health delivery.

PMID- 9633137
TI  - [Reorganising specialist care in the Ciutat Vella Health Sector: analysis of an
      experience].
AB  - OBJECTIVE: Analysis of the results obtained in terms of improvement in the
      continuity of care, its resolutive capacity and accessibility, in the framework
      of the organisational change brought about by the reorganisation of specialist
      care (RSC) in the Ciutat Vella Health Sector. DESIGN: A descriptive study of the
      reorganised model of specialist care introduced in 1995 and comparison between
      this and the previous model (1993) in terms of activity, further tests made,
      referral to hospital, filling in the clinical history and waiting-list. T
      SETTING: The experience involved 4 PCTs in the Ciutat Vella Health sector of
      Barcelona (covering 74,449 people). MEASUREMENTS AND MAIN RESULTS: The volume of
      visits was in general less in 1995, while other types of activity had been
      incorporated: minor surgery, cryotherapy, consultations and sessions.
      CONCLUSIONS: The model of RSC satisfies the basic objectives for which it was
      designed. It increased the specialist's ability to resolve the case within
      Primary Care. It improved user accessibility to specialist care in terms of
      waiting time. Finally, the model favours ongoing care, thanks to a single
      clinical history for both levels.

PMID- 9633138
TI  - [Drug dependent patients in the methadone maintenance program: evaluation in
      primary care of psychosocial and organic severity].
AB  - OBJECTIVE: To describe the profile of bio-psycho-social gravity in opiate
      dependent patients in the Methadone Maintenance Programme. DESIGN: A descriptive
      crossover study. SETTING: Primary Care Centre. PATIENTS: 31 heroin-dependent
      patients on Methadone treatment at a drug-dependency care centre who attended the
      Health Centre for drug dispensing, between February and December 1996.
      MEASUREMENTS AND MAIN RESULTS: All patients were given the semi-structured
      clinical interview Opiate Treatment Index (OTI) and filled in the self
      administered APGAR family questionnaire. 48.3% had little deterioration in their
      "General Health Status" section and 54.8% had low scores in "Conduct causing risk
      of HIV contagion". CONCLUSIONS: The observed data are consistent with the results
      to be expected in this kind of programme. The multidimensional evaluation
      instruments are a tool that can be used to tackle drug-dependent patients in
      Primary Care.

PMID- 9633139
TI  - [Construction and initial validation of a research attitude questionnaire in
      primary care].
AB  - OBJECTIVE: To construct and validate a research attitude questionnaire in primary
      care physicians. DESIGN: Validation study of a attitude questionnaire. SETTING:
      Teaching health centres of family medicine in Valencia (Spain). SUBJECTS: All the
      physicians (253) of 18 centres: family and general physicians, pediatricians and
      third-year family residents. MEASUREMENTS AND RESULTS: It was constructed a five
      Likert scale of 31 items and two dichotomic items. Pretest phase to 25
      physicians. Validation Phase: 1. Reliability: a) Spearman-Brown correlation
      coefficient item-global and Cronbach coefficient; b) test-retest through
      comparing item punctuation and global. 2. Content validation; construction
      validation through exploratory factorial analysis and method of extreme groups
      (research or no) [corrected]. One hundred and fifty physicians (59.3%) answered
      the first contact, and 107 (71.3%) of them, the second contact. The questionnaire
      evidenced good internal consistency (alpha = 0.82) and time stability. Five
      factors were extracted that explained 58.7% of variability: research integration
      in primary care, self-capacity in study development, subjectives barriers,
      perception of education's need in research methodology, and structural barriers.
      Three factors showed significant differencies between extreme groups [corrected].
      Definitive questionnaire of 20 items. CONCLUSIONS: The questionnaire is a valid
      and reliable instrument to know the research attitude of primary care physicians.

PMID- 9633140
TI  - [Vaginal candidiasis: diagnosis and treatment in a primary care clinic].
AB  - OBJECTIVE: To assess the frequency of Candida species others than Candida
      albicans isolation, in patients with chronic as well as relapsing vaginitis. To
      analyze the clinical pictures and the treatments routinely employed in patients
      with Candida albicans infection, compared to those with other Candida species
      infection, in a Primary Care Clinic. DESIGN: Prospective, comparative, transverse
      study. SETTING: Primary health center from January, 1995 to May, 1997. MATERIAL:
      Two hundred and thirty four women (234) in ages between 16 and 55 years, with
      cervicovaginitis and a positive culture to any species of Candida, were the
      subject of the present study. RESULTS: From the total of 234 patients studied,
      142 (60.5%) were infected by Candida albicans and 92 (39.5%) by other Candida
      species; no difference in symptomatology was recorded in both groups. Nistatine
      alone or combined with imidazole derivatives were the antimycotics more commonly
      employed, with Candida albicans resistance of 9.6% in the first case and 11.2% in
      the second one. CONCLUSIONS: It is stressed the importance that has the
      identification of Candida species causing vaginitis. It is also acknowledged the
      well handled treatment, despite of the species to be treated.

PMID- 9633142
TI  - [Health care delivery system for the frail elderly developped in Quebec: SIPA
      experience].

PMID- 9633143
TI  - [Interest in home care].

PMID- 9633144
TI  - [Postcoital contraception].

PMID- 9633145
TI  - [How do we diagnose cervical cancer].

PMID- 9633146
TI  - [Acceptance of nicotine-substitute treatment].

PMID- 9633147
TI  - Use of the bispectrum to analyse properties of the human electrocardiograph.
AB  - The bispectrum and bicoherence spectrum have been shown to be powerful techniques
      for identifying different types of nonlinear system responses. This paper
      presents an introduction to bispectral techniques applied to biomedical signals
      and examines the bispectral properties of the human electrocardiograph (ECG). The
      bispectrum proves to be an effective tool for representing and distinguishing
      different ECG response types. Bispectral ECG analysis is non-invasive and may
      prove to be a useful discriminant diagnostic.

PMID- 9633148
TI  - Monte Carlo dosimetry of the microselectron HDR 192Ir brachytherapy source using
      MCNP4A.
AB  - This study examines the transverse radial dose distribution around the Nucletron
      MicroSelectron high dose rate (HDR) 192Ir brachytherapy source using the Monte
      Carlo radiation transport code MCNP (Monte Carlo N Particle) version 4A. The
      geometry modeled consisted of an identical simulation of the geometry of the
      MicroSelectron HDR source within the centre of a cylindrical water phantom of 80
      cm diameter and height. Doses were calculated at 0.1 cm intervals in the 1 cm
      closest to the source, whilst extending to 1 cm intervals 15 cm from the source.
      Conversion to the clinically relevant unit of air-kerma strength to describe
      source activity enables absolute comparison of Monte Carlo dose calculations to
      current treatment planning computer results. Most HDR brachytherapy planning
      computers utilise algorithms based on a point source with attenuation and scatter
      corrections based on the Van Kleffen and Starr or Meisberger equations.
      Significant differences between the planning computer algorithms and the Monte
      Carlo dose calculations occur in the near field (radius less than 1 cm) and the
      far field (radius greater than 8 cm) which in some cases may have important
      clinical consequences. These results are consistent with Monte Carlo calculations
      of previous authors examining the MicroSelectron HDR 192Ir source and also show
      that far field uncertainties are increased as the size of the phantom is reduced
      to a more realistic patient size.

PMID- 9633149
TI  - Radioactivity measurements of ytterbium-169 brachytherapy sources.
AB  - Ytterbium-169 is being considered as a new radiation source for brachytherapy
      applications. This radioisotope emits photons with energies ranging from 50 to
      308 keV (average energy 93 keV) and decays with a half life of 32 days. For these
      reasons, it is believed to offer radiological and radiobiological advantages over
      some other isotopes currently in use. One impediment to widespread clinical use
      of this isotope is the determination of source strength in units of air kerma
      rate [cGy h-1]. The source strength can be measured directly with an ion chamber
      or calculated indirectly from the source radioactivity [Bq] with corrections for
      encapsulation. Our attempts to reconcile these two approaches have led to the
      development of a spectrometric technique for determining the radioactivity of
      ytterbium-169 brachytherapy seeds. A High Purity Germanium (HPGe) spectrometer is
      used to count the 307.7 keV photon emitted within a defined solid angle. The
      intrinsic photopeak efficiency of the detector was determined by Monte Carlo
      simulation followed by experimental verification with an activity-calibrated
      europium-152 source. Finally, the HPGe system has been used to calibrate a re
      entrant ionisation chamber, allowing routine of Ytterbium source activity for
      clinical applications.

PMID- 9633150
TI  - An investigation into lung correction for tangential breast irradiation.
AB  - A solid water breast phantom with a lung equivalent material was constructed to
      investigate interface effects of 6 MV tangential photon fields. The phantom was
      built so that Thermo-luminescence Dosimeters (TLD) could be used for comparison
      to a pencil beam and Equivalent Tissue-Air-Ratio (ETAR) algorithms. The
      investigation highlighted the limitations in both of these algorithms under
      clinically anatomical conditions. At the lung/tissue interface both algorithms
      showed errors between 3-12% depending on the position of the TLD. In tissue
      greater than 1 cm from the interface region the errors on average were within +/-
      5%. Dose comparisons in lung tissue showed similar results to the interface
      region. These results indicate that normalisation of Reference Dose in the
      interface region for tangential breast treatments cause over or under estimates
      of dose.

PMID- 9633151
TI  - Determination of CT scanner radiation output: correction factors for partial
      irradiation of thimble and pencil ionisation chambers by collimated fan beams.
AB  - CT radiation output (mGy mAs-1) measured free-in-air on axis is required for
      compliance testing protocols. It can also be used as an input parameter for
      computer programs for patient dose assessment for a range of CT examinations.
      Output correction factors have been investigated as a function of collimation
      width for two chambers; an in-beam, 6 cc general diagnostic chamber, and a 3 cc
      pencil CT chamber. For irradiation by a fan beam perpendicular to the chamber
      axis, a correction factor given by the ratio, chamber active length to beam
      collimation width, is applicable to within +/- 5% of a measured ratio for the
      pencil CT chamber. However, this is not the case for the short 6 cc thimble
      chamber where an exponential function was found to fit the data to within similar
      limits. It is recommended that a pencil chamber be used for determining radiation
      output in air for a CT scanner. For a given scan condition static measurements
      are only required, obviating a need for sequential movements of an occluded small
      volume chamber to sample a radiation profile.

PMID- 9633152
TI  - Monte Carlo simulation of tuning capacitor selection in a cochlear implant.
AB  - The principles of Monte Carlo simulation are applied to critical manufacturing
      process in the construction of cochlear implants. In this application, the tuning
      of the implant's radio frequency (RF) communication system is dependent upon a
      "select on test" tuning capacitance. The aim is to accurately predict the usage
      of capacitors of a given size in future production of cochlear implants using
      Monte-Carlo simulation. The predicted quantities may then be purchased from a
      supplier to satisfy the requirements of high volume manufacturing without
      maintaining unnecessary and expensive stock levels of infrequently or never used
      capacitors. Simulations indicate that for large production runs, prediction of
      the necessary quantities of particular tuning capacitor sizes may enable the
      implant manufacturer to reduce their capacitor stock levels by as much as 82
      percent. This significant reduction is in comparison to maintaining a uniform
      stock level of all sizes of capacitors, assuming random probability of requiring
      each size of tuning capacitor.

PMID- 9633153
TI  - Intra- and interrater variation in the evaluation of videofluorographic
      swallowing studies.
AB  - The objective of this study was to determine the inter- and intrarater
      reliability in evaluating videofluoroscopic swallowing studies (VFSS).
      Participants included 4 physicians (3 physiatrists and 1 internist) and 5 speech
      language pathologists with at least 5 years experience in evaluating VFSS. The
      main outcomes of the study were reliability ratios of positive and negative tests
      in inter- and intrarater evaluations. Raters independently rated each of 20 VFSS
      on two separate occasions. Traits evaluated included oral stage impairment,
      aspiration, pharyngeal retention, and several functional components: timing of
      swallow onset, adequacy of velopharyngeal apposition, laryngeal elevation,
      epiglottic tilt, pharyngeal contraction, and pharyngoesophageal (PE) segment
      opening. Reliability varied widely depending on food type and the trait under
      evaluation. Inter- and intrarater reliability ratios did not differ widely.
      Reliability ratios values typically were highest (greater than 90%) for
      aspiration, especially with solid food, and lowest for the functional components.
      It was concluded that inter- and intrarater reliability in VFSS are adequate for
      evaluating oral stage, laryngeal penetration, and aspiration and pharyngeal
      retention, but questionable for functional components.

PMID- 9633154
TI  - Observer variation in evaluation of videofluoroscopic swallowing studies: a
      continuing problem.

PMID- 9633155
TI  - Weight loss, dysphagia, and outcome in advanced dementia.
AB  - There has been much debate on the value and risks of long-term enteral feeding in
      patients with advanced dementia. A retrospective study was carried out on 47
      patients with a primary diagnosis of dementia who died over a two-year period.
      All were inpatients in a nursing home or skilled nursing facility. Marked weight
      loss and dysphagia occurring in a specific pattern were found to be associated
      with death from pneumonia. These clinical features probably imply failure of
      basic homeostatic mechanisms. Patients showing this clinical pattern may be less
      likely to show benefits from long-term enteral feeding.

PMID- 9633157
TI  - Electromyographic response of the labial muscles during normal liquid swallows
      using a spoon, a straw, and a cup.
AB  - In this investigation, surface electromyographic (EMG) recordings were used to
      make qualitative and quantitative analyses of labial muscle activity during three
      swallowing tasks, incorporating the use of various drinking implements. EMG was
      recorded from four quadrants of the perioral region and from the submental muscle
      complex in 11 normal adult females. Swallowing tasks included liquid extraction
      from a spoon, a straw, and a cup and posterior bolus propulsion of a 5 ml, thin
      liquid. Average EMG values obtained during a maximal lip compression task were
      used to normalize labial muscle responses for each subject thus allowing between
      subject comparisons. Variable activity patterns were noted in the perioral
      muscles once the lips were contacted by a drinking implement. Subjects used a
      greater percentage of maximal labial muscle activity to remove liquid from an
      implement than to swallow the liquid. A greater level of EMG was recorded in the
      lips during straw usage as compared with spoon or cup usage. Significant
      intrasubject and intersubject variability in labial function occurred during
      liquid removal using a drinking implement and during the oral swallow in these
      normal subjects.

PMID- 9633156
TI  - Reflexogenic areas for velopharyngeal closure in rabbits.
AB  - Responsive areas for velopharyngeal closure were examined by recording
      diaphragmatic and superior pharyngeal constrictor activities of anesthetized
      rabbits. Pressure stimulation was applied with a cotton applicator to the mucosae
      of three pharyngeal areas: the anterior (palatal) and posterior walls of the
      nasopharynx and the posterior wall of the oropharynx. The intensity and duration
      of the stimulation were around 9.0 gf and 0.43 sec, respectively. Velopharyngeal
      closure was elicited more frequently from the posterior wall of the nasopharynx
      than the other two areas tested. The higher responsiveness of the posterior wall
      of the nasopharynx for velopharyngeal closure is suggested to be attributed to
      higher density and/or lower threshold of pressure receptors in this area than
      those in the other two areas tested. Possible physiological implications of the
      present results are discussed.

PMID- 9633158
TI  - Tracheotomy tube occlusion status and aspiration in early postsurgical head and
      neck cancer patients.
AB  - The purpose of the present study was to investigate tracheotomy tube occlusion
      status and prevalence of aspiration utilizing videofluoroscopy. A prospective
      study was done of 16 consecutive, early, postsurgical head and neck cancer
      patients with tracheotomy. Selection criteria included the ability to tolerate
      tracheotomy tube occlusion prior to and during the modified barium swallow
      procedure, oral and/or pharyngeal surgical resection, no history of neurological
      disease or stroke, and medical clearance to begin oral feeding. There was 100%
      agreement among the independent reviewers on ratings of the presence or absence
      of aspiration. It was found that occlusion status of the tracheotomy tube did not
      influence the prevalence of aspiration in the immediate postoperative period. No
      trends were observed when comparing bolus consistency, type of tracheotomy tube,
      or presence/absence of a nasogastric tube and the ratings of aspiration.

PMID- 9633159
TI  - Swallowing problems in the nursing home: a novel training response.
AB  - Various studies suggest that between 50% and 75% of nursing home residents have
      some difficulty in swallowing. Some of these residents are assessed and treated
      by speech pathologists, but many are managed by nursing staff without specialist
      input. A training program called Swallowing ... on a Plate (SOAP) has been
      developed by the Centre for Education and Research on Ageing and the Inner West
      Geriatrics and Rehabilitation Service to help address swallowing-related problems
      in local nursing homes (Inner West of Sydney, Australia). The training program
      teaches nursing staff how to identify, assess, and manage swallowing problems,
      including making appropriate referrals. Several new instruments were developed
      specifically for this program including two assessment checklists, a set of
      management guidelines, and a swallowing care plan. Evaluation of the program-
      including 3 months follow-up--showed it to be highly successful. A stand-alone
      training resource has been produced for wide distribution to help staff implement
      the program as a permanent aspect of their nursing care. This paper describes the
      development, content, presentation, resource, and evaluation of the above
      program.

PMID- 9633160
TI  - Motor innervation of the cricopharyngeus muscle by the recurrent laryngeal nerve.

PMID- 9633161
TI  - The risk factors and impact on survival of feeding tube placement in nursing home
      residents with severe cognitive impairment.

PMID- 9633162
TI  - False-positive results on videofluoroscopy.

PMID- 9633163
TI  - Functional occlusal relationships in a group of post-orthodontic patients:
      preliminary findings.
AB  - This study investigated features of the functional occlusion in a group of 37
      patients immediately following two-arch fixed appliance treatment. Study casts
      were mounted in the retruded axis position on a semi-adjustable articulator and
      occlusal contacts were recorded with articulating paper in retruded and lateral
      mandibular positions. The magnitude of the slide between the retruded axis
      position and the intercuspal position was measured to the nearest 0.5 mm in the
      antero-posterior, vertical and lateral directions. The results revealed that the
      majority of subjects had a unilateral contact on initial closure in the retruded
      axis position, and a slide between this position and the intercuspal position.
      Most subjects demonstrated canine guidance on the working side in lateral
      positions. In addition, however, most subjects had contact between the second
      molars on the non-working side. Based on current concepts of functional
      occlusion, this group of post-orthodontic patients did not exhibit ideal occlusal
      relationships. The long-term implications of this finding are unclear, but may be
      associated with post-orthodontic instability, tooth wear and temporomandibular
      disorders. A long-term follow-up is planned to attempt to clarify some of these
      issues.

PMID- 9633164
TI  - Non-surgical treatment of upper airway obstruction in oculoauriculovertebral
      dysplasia: a case report.
AB  - A non-surgical technique for the treatment of upper airway obstruction in
      oculoauriculovertebral dysplasia using an intra-oral orthopaedic appliance is
      described, which resulted in respiratory and feeding problems being solved
      without side-effects. This non-invasive management might also be of major benefit
      in the treatment of airway obstruction associated with Pierre Robin sequence,
      mandibular micrognathia in other craniofacial anomalies, or obstructive sleep
      apnoea.

PMID- 9633165
TI  - Alveolar bone grafting: a review of 115 patients.
AB  - The results of alveolar bone grafting carried out at The Hospital for Sick
      Children, Great Ormond Street, London, UK, between January 1982 and January 1989
      were assessed. Cancellous bone from the iliac crest was grafted to alveolar cleft
      defects in 115 patients (63 male and 52 female). Eighty-seven unilateral (58 left
      and 29 right) and 28 bilateral clefts were operated on. The mean age at the time
      of operation was 11.5 years, with a range of 8.08-18.75 years. The cleft canine
      had erupted prior to bone grafting in 58.4 per cent. At the time of this study
      the cleft had erupted in 96.35 per cent and was unerupted in 3.65 per cent of
      sites. Radiographs were taken at regular intervals and assessed according to
      previously reported criteria. Eighty-six per cent were clinically successful
      (Type I and II). In Type III 10.95 per cent had less than three-quarters of the
      normal interdental septal height and 2.18 per cent failed (Type IV). In addition,
      3.6 per cent of sites showed cervical root resorption affecting the adjacent
      incisor and 1.4 per cent internal resorption of the cleft canine.

PMID- 9633166
TI  - The role of lateral cephalometric radiography and fluoroscopy in assessing
      mandibular advancement in sleep-related disorders.
AB  - Mandibular advancement splints are successful in managing obstructive sleep
      apnoea (OSA) in selected subjects. For these to be effective, some improvement in
      the dimensions of the oropharyngeal airway must occur. Twenty subjects with
      proven obstructive sleep apnoea were examined using lateral cephalometric
      radiography and a fluoroscopic technique. Cephalograms were analysed, and
      assessed for both skeletal and soft tissue abnormalities known to be present in
      OSA subjects. On the basis of these, a prediction was made as to whether the
      subject's oropharyngeal airway would increase during mandibular protrusion. From
      the fluoroscopic sequences, the narrowest antero-posterior dimensions of the post
      palatal and post-lingual airways were recorded as the mandible moved from the
      intercuspal position into maximal protrusion. The changes in airway size were
      noted and these were compared with the predictions made from the static films. In
      nine subjects, fluoroscopy indicated that the airway opened well during
      mandibular protrusion, seven did not improve and in four the changes were
      minimal. Post-palatally the mean airway increase was 2.6 mm, whilst behind the
      tongue a mean improvement of 3.1 mm was seen. In all but two instances, the
      cephalometric prediction agreed exactly with the outcome demonstrated by
      fluoroscopy. All subjects whose airways clearly increased were correctly
      identified by the cephalogram alone. Cephalometric features associated with a
      good airway response to protrusion were a reduced lower facial height, low
      maxillomandibular planes angle and a high hyoid position, accompanied by a normal
      anteroposterior relationship of the jaws, relatively normal mandibular body
      length and soft palate area. The more abnormal the skeletal and soft tissue
      dimensions, the poorer the prognosis. Thus, whilst a single radiograph could
      indicate whether a positive mandibular response to protrusion could be expected,
      where doubt existed, a fluoroscopic analysis could provide a useful adjunct to
      diagnosis.

PMID- 9633167
TI  - Natural head posture, upper airway morphology and obstructive sleep apnoea
      severity in adults.
AB  - Enlarged tonsils, adenoids, and chronic respiratory problems have been associated
      with the compensatory adaptations of natural head posture (NHP) in children.
      Recently, it has been shown that adult patients with Obstructive Sleep Apnoea
      (OSA) also tend to exhibit a craniocervical extension (CCE) with a forward head
      posture (FHP). This study was designed to search for some characteristics of OSA
      patients that may be related to these adaptive changes in NHP. Overnight
      polysomnographic, demographic, and cephalometric records of 252 adult male
      subjects with various types of skeletal patterns and dental conditions were
      examined. Apnoea Index (AI) and Apnoea + Hypopnoea Index (AHI) variables were
      assessed to separate the non-apnoeic snorers (n = 35), and mild (n = 101),
      moderate (n = 63), and severe (n = 53) OSA groups. Results of the Tukey tests
      revealed that severe OSA patients had a greater tendency to exhibit a CCE with a
      FHP (P < or = 0.05 to P < or = 0.001). Differences in head extension (NSL.VER)
      between groups could not be identified. Pearson's 'r' correlation coefficients
      revealed that the CCE and FHP in OSA patients were associated with a higher
      disease severity, a longer and larger tongue, a lower hyoid bone position in
      relation to the mandibular plane, a smaller nasopharyngeal and a larger
      hypopharyngeal cross-sectional area, and a higher body mass index (P < or = 0.05
      to P < or = 0.001). It is concluded that a CCE with a FHP is more likely to be
      seen in severe and obese OSA patients with certain morphological characteristics
      of the upper airway and related structures.

PMID- 9633168
TI  - Treatment difficulty and treatment outcome in orthodontic care.
AB  - The influence of perceived treatment difficulty on the outcome of and investment
      in orthodontic treatment was studied in 19-year-old individuals treated by
      general practitioners or specialists within the totally subventioned Swedish
      system for orthodontic care. A total of 313 individuals were evaluated according
      to treatment outcome and treatment investment. About one-quarter of the
      treatments evaluated were classified as easy, one-quarter as moderately
      difficult, and one-half as difficult. The perceived treatment difficulty was on a
      group basis associated with the pretreatment need. The treatment outcome became
      less favourable and the treatment investment more expensive the greater the
      perceived difficulty. More than one-quarter of the treatments provided by general
      practitioners were classified as difficult compared with three-quarters of those
      provided by specialists. The outcomes were, in general, more favourable for
      specialist treatments than for those provided by general practitioners, although
      the individuals treated by specialists, on the average, were classified as more
      difficult than those provided by general practitioners. Easy treatments were
      found to be extremely cost-effective and should be carried out when possible.
      General practitioners should preferably treat uncomplicated cases, and an
      increased use of fixed appliances would be desirable in the treatment of
      moderately difficult treatments. Difficult cases should be treated exclusively by
      specialists. Cases with little need or benefit of treatment, or a poor prognosis
      should be given low treatment priority, and patients and parents should in these
      cases be informed about the small expected benefit and risks involved.

PMID- 9633169
TI  - The influence of operator changes on orthodontic treatment times and results in a
      postgraduate teaching environment.
AB  - There is some concern that patients treated by postgraduate students during their
      specialty training may be disadvantaged in the quality of treatment result and
      subject to longer treatment times if they are treated by more than one operator.
      This study analysed the pre- and post-treatment study models of orthodontic
      patients from a district general hospital department, debonded by one junior
      member of junior staff in the calendar years 1991 and 1992. All patients were
      treated using the same pre-adjusted edgewise appliance in both arches. Two groups
      of patients were identified: patients whose treatment was started and finished by
      the same operator (registrar A), and those whose treatment was begun by another
      operator (registrar B), but finished by registrar A. A random sample of 30
      patients from each group was selected and the study models at the start and end
      of treatment were scored using the PAR (Peer Assessment Rating) Index. No
      significant differences were found between the average PAR scores for each group
      at the beginning of treatment, or between groups A and B at the end of treatment;
      the average treatment time for the patients treated by one operator was 17.67
      months (SD 4.15 months), while the average treatment time for the patients
      treated by more than one operator was 26.1 months (SD 6.78 months).
      Statistically, this difference was highly significant (P < 0.001). A highly
      linear relationship (R2 = 0.92) was found between the percentage PAR score
      reduction and the initial PAR score. The findings and their implications are
      discussed.

PMID- 9633170
TI  - The effect of environmental factors on elastomeric chain and nickel titanium coil
      springs.
AB  - It is well known that elastomers exhibit viscoelasticity and as such have their
      mechanical properties modified by temperature. Nickel titanium archwires are also
      affected by temperature and have been modified with specific temperature related
      properties for clinical use. What is less well known is the effect that other
      environmental factors, such as food, might have on the force delivery properties
      of both elastomeric materials and nickel titanium coil springs used for space
      closure. For instance gross colour change in elastomeric chain is a common
      clinical finding in patients who consume spiced foods. The aim of this work was
      to determine the effect three common environmental factors namely, water, Coke,
      and turmeric solution have on elastomeric chain and nickel titanium coil springs.
      In addition, it was decided to re-examine the effect of temperature at 10, 22,
      and 37 degrees C on both these space closing materials. Unlike many previous
      investigations, the test specimens were held at a constant stretch throughout the
      test period, including during their transfer to the Instron Universal Testing
      machine for force measurement. Six force measurements were made over the first
      hour, then at 24 hours and 7 days. A control group of dry specimens, maintained
      at 22 degrees C, had additional measurements made weekly for a 4-week period. The
      results indicated that elastomeric chain was affected by all the test
      environments while nickel titanium springs were only affected by temperature.

PMID- 9633171
TI  - Shear bond strengths of ceramic brackets bonded with different light-cured glass
      ionomer cements: an in vitro study.
AB  - The purpose of this study was to evaluate the shear bond strengths of four light
      cured glass ionomer cements used for direct bonding of ceramic brackets, and to
      compare the results with a two-paste chemically-cured composite resin. Two
      commercially available polycrystalline ceramic brackets, with either chemically
      or mechanically retentive bracket bases, were evaluated. The brackets were bonded
      to 100 freshly extracted bovine incisors, and, after storage in tap water at room
      temperature for 24 hours, they were subsequently tested in a shear mode using a
      universal testing machine. The maximum bond strength and the site of bond failure
      were recorded. With the mechanically retentive base, Fuji Ortho LC produced the
      highest bond strength (18.50 MPa), which was not significantly different from the
      values achieved with Concise (14.88 MPa) (P > 0.1) and Photac Bond (13.86 Mpa) (P
      = 0.1). The lowest bond strength was provided by locomp A20 (5.23 MPa). With the
      chemically retentive base, the highest bond strength was measured with Concise
      (29.27 MPa), which was significantly (P < 0.01) higher than the values for Photac
      Bond (16.27 MPa) and Fuji Ortho LC (13.48 MPa). Again locomp A20 produced the
      lowest bond strength (3.21 MPa). Three cements (Dyract Ortho, locomp A20 and Fuji
      Ortho LC) provided higher shear bond strengths with the mechanical retention
      system, whereas Concise and Photac Bond gave higher strengths with the silane
      treated bracket bases. However, the strengths were statistically significantly
      different only for locomp A20 (P = 0.001) and Concise (P = 0.001). With the
      mechanically retentive base, Dyract Ortho and locomp A20 failed at the enamel
      adhesive interface, whereas Photac Bond and Concise debonded at the bracket
      adhesive interface. Fuji Ortho LC failed at both, the bracket-adhesive (40 per
      cent) and the adhesive-enamel (60 per cent) interface. With the chemically
      retentive base, all the adhesives failed at the enamel-adhesive interface. Only
      one bracket fracture occurred in this study, and no enamel damage was detected.

PMID- 9633172
TI  - An epidemiological survey using the Treatment Priority Index (TPI).
AB  - The purpose of this study was to evaluate the prevalence of malocclusion and to
      assess the need for orthodontic treatment among 6-10 year old Turkish primary
      school children. The Treatment Priority Index (TPI) was used to record and
      measure the malocclusions. The findings were that 40.38 per cent of the observed
      population showed normal occlusion, 21.85 per cent had minor manifestations of
      malocclusion and treatment need was slight, 25.17 per cent of the subjects showed
      definite malocclusion, 7.54 per cent had severe malocclusion and 5.06 per cent
      had a very severe handicap with a mandatory treatment requirement. Orthodontic
      treatment need increased between 6 and 10 years of age. No statistically
      significant difference was found between the mean TPI values of male and female
      subjects.

PMID- 9633173
TI  - Bonding to molars--the effect of etch time (an in vitro study).
AB  - This study evaluated the effect of etch time on the shear bond strength obtained
      when bonding to the buccal enamel of first molar teeth. Recently extracted first
      molar teeth were etched with 37 per cent phosphoric acid gel for 15, 30 and 60
      seconds. Preformed cylinders of Concise composite resin were then bonded to the
      buccal surfaces of the molar teeth. After storage in water for 24 hours at 37
      degrees C, the specimens were debonded in a direction parallel to the buccal
      surface. Examination of the shear bond strengths showed significant differences
      in shear bond strength between 15 and 30 seconds (P < 0.01) and between 15 and 60
      seconds (P < 0.001). Weibull analysis revealed that the probability of bond
      survival increased as etch time increased, however, the difference between 30 and
      60 seconds was not statistically significant. The results indicate that, despite
      current recommendations of a 15-second etch for premolars, canines and anterior
      teeth, an etching time of at least 30 seconds should be used when bonding to the
      buccal surfaces of first molars. A further increase in etching time to 60 seconds
      produces no significant increase in bond strength.

PMID- 9633174
TI  - Use of glass-ionomers for bracket bonding--an ex vivo study evaluating a testing
      device for in vivo purposes.
AB  - Seven glass-ionomer cements were tested and compared with a composite resin in
      order to find the glass-ionomer cement with the highest bond strength to enamel
      with normal anatomy and composition (not ground). Five types of surface treatment
      were used. The results show that Aqua Cem and Ketac Cem, both water-hardening,
      present the highest bond strength, followed by the conventional glass-ionomer
      cement Fuji IIF. Surface treatment according to the manufacturers' instructions
      and surface treatment with polyacrylic acid were found to give rise to the
      highest bond strength for all of the seven cements. However, none of the glass
      ionomer cements reached the values for the composite resin Concise. The testing
      instrument designed for ex vivo purposes measured with high precision and
      accuracy and with a low methodological error.

PMID- 9633175
TI  - [Cost effectiveness of the treatment of chronic hepatitis C with interferon
      alpha].
AB  - The purpose of this study was to assess the cost-effectiveness of the treatment
      of chronic hepatitis C with interferon in Spain. Disease progression was studied
      using a Markov model through which an untreated cohort of 1000 patients was
      compared with cohorts treated with interferon 3 MU three times per week for 6, 12
      or 18 months. Treatment cost, patients quality of life, and survival were the
      parameters evaluated. Using the perspective of the National Health System, an 18
      month treatment with alfa interferon offers a better cost-effectiveness ratio
      than a treatment of 6 or 12 months duration. The age of the patient at the start
      of treatment is one of the most influential factors on the cost-effectiveness of
      treatment. In patients under 45 years of age, a net cost saving is observed with
      all treatment schedules, especially with 18 months treatment, due to significant
      reductions in severe complications of disease progression. In patients aged 45
      60, 18 months treatment incurs a net cost, although important gains are made in
      survival and quality of life. In patients over 65 years of age, the economic
      benefits of prolonged treatment do not compensate the extra cost. In conclusion,
      treatment of chronic hepatitis C with alfa interferon should begin as early as
      possible, especially in young patients. In cases of favourable response,
      treatment should be extended to 18 months, in order to obtain a higher rate of
      sustained response, avoid progression of hepatic disease and achieve a more
      favourable cost-effectiveness ratio.

PMID- 9633176
TI  - [Significance of the determination of antineutrophil cytoplasmic antibodies
      (ANCA) in ulcerative colitis and Crohn's disease].
AB  - We have studied prospectively 126 consecutive patients recruited with a known
      diagnosis of ulcerative colitis (UC; n = 78) and Crohn's disease (CD; n = 48) for
      anti-neutrophil cytoplasmatic antibodies (ANCA) by indirect immunofluorescence
      (IFI). Forty-six percent of UC and 18% of CD patients were found positive. The
      sensitivity and specificity for UC diagnosis were 0.46 and 0.81, respectively. We
      evaluated the pattern of IFI exhibited (perinuclear: pANCA and cytoplasmatic:
      cANCA). cANCA was found in 77% of CD and in only 30% of UC patients (p = 0.01).
      Sera from all CD patients were positive at a 1:20 dilution (and not at higher
      dilution) and it occurred in only in 14 UC patients (30%). Positive sera were
      also tested to characterize the antigen specificity by enzyme-linked
      immunosorbent assay (ELISA) but the antigenic nature of ANCA could not be
      identified in most cases. No differences were found between ANCA positive and
      ANCA negative patients regarding colonic extension (UC) or colonic involvement
      (CD), activity and colectomy. We conclude that ANCA may be a helpful diagnostic
      test in UC patients but it not seems to be important as a marker of activity.
      ANCA positivity can reflect disease heterogeneity in UC patients, perhaps
      discriminating those with immunologic disturbances.

PMID- 9633177
TI  - [Magnetic resonance cholangiopancreatography (MRCP) versus endoscopic retrograde
      cholangiopancreatography (ERCP): diagnostic usefulness].
AB  - Magnetic resonance cholangiopancreatography (MRCP) is a new noninvasive technique
      to examine the biliopancreatic tract that have a high diagnostic accuracy. Thus
      it becomes an appealing modality that can avoid invasive approaches. The purpose
      of this study was to evaluate the sensitivity and specificity of MRCP in
      comparison to endoscopic retrograde cholangiopancreatography (ERCP). We studied
      41 patients (24 male, 17 female), median age 64.2 years (range 20 to 86 years),
      in which MRCP and later ERCP were performed; results of both techniques were
      compared. In the assessment of biliary tract (n = 39), sensitivity/specificity
      was 100/94.4% in normal bile ducts (n = 18); 100/100% in choledocholithiasis (n =
      13); 100/100% in sphincter of Oddi dysfunction (n = 2), and 100/83.3% in neoplasm
      (3 ampullary tumors, 2 cholangiocarcinomas). In the evaluation of pancreatic duct
      (n = 32), sensitivity/specificity was 100/95.8% in normal pancreatic duct (n =
      23); 80/100% in chronic pancreatitis (n = 5), and 100/75% in pancreatic carcinoma
      (n = 3). MRCP has very high sensitivity and specificity in the evaluation of the
      biliary and pancreatic ducts, and can avoid to perform purely diagnostic ERCP,
      although further studies are required to better assess the effectiveness of the
      technique.

PMID- 9633178
TI  - [Duodenal Crohn's disease: diagnostic and therapeutic complexity].
AB  - Crohn's disease may involve any area of the digestive tract, but its localization
      in the duodenum is rare. The clinical, radiological or endoscopic findings may
      simulate those of peptic ulcer and histologic examination is not diagnostic. In
      contrast with Crohn's disease of any other localization, the formation of
      fistulas is exceptional. The authors present one case of duodenal Crohn's disease
      the unspecific symptomatology of which deviated the original orientation towards
      the more common diseases. Steroid treatment was not sufficient to control the
      disease which led to complications with the formation of an enterocutaneous
      fistula. The association of azathioprine was very effective not only in achieving
      remission of the process, but also in resolving the complications.

PMID- 9633179
TI  - [Gaucher's disease suspected by abdominal echography findings].
AB  - Abdominal ultrasonographic findings of Gaucher's disease had been reported, but a
      specific pattern has not been described. We report here a patient with an
      abdominal sonographic pattern which was concluded to be strongly suggestive of
      Gaucher's disease: solid focal splenic lesions with different patterns
      (hypoechoic, hiperechoic and mixed nodules associated with hypoechoic irregular
      areas) and bright liver and spleen echo pattern with posterior beam attenuation.
      Gaucher's disease was subsequently confirmed by determination of leukocyte beta
      glucosidase activity and mutations of glucocerebrosidase gene.

PMID- 9633180
TI  - [Pancreatic abscess caused by Candida following wide-spectrum antibiotic
      treatment].
AB  - Pancreatic infection by Candida is an infrequent entity. We report two cases and
      review literature. A 67 year-old woman who was admitted for severe acute
      pancreatitis of biliary origin developed high fever during fourth week of stay;
      it was secondary to a pancreatic abscess due to Candida. On the other hand, a 67
      year-old man with severe acute biliary pancreatitis and renal insufficiency
      showed an abscess of similar characteristics that was identified during fourth
      week of evolution. Both of them recovered completely after surgical drainage and
      antifungical parenteral treatment. The use of broad spectrum antibiotics recently
      recommended for prophylaxis of pancreatic infection in patients with necrotizing
      acute pancreatitis, can favour opportunistic infection by several agents.
      Pancreatic abscesses by Candida often occurs in patients receiving broad spectrum
      antibiotics, although it isn't an essential condition. The fact that Candida
      could be only a contaminant may delay diagnosis and early treatment, and then it
      can determine a poor outcome. Adequate treatment is urgent surgical drainage
      associated with antifungical parenteral therapy. Usefulness of antifungic drugs
      in patients undergoing long term antibiotic prophylaxis for secondary infection
      must be evaluated.

PMID- 9633181
TI  - [Chronic cholestasis as a presentation form of portal cavernoma].
AB  - A 37 year-old-woman was evaluated in 1993 for a chronic asymptomatic cholestasis.
      An endoscopic retrograde cholangiopancreatography showed the biliary tract
      compressed, and a mesenteric angiogram disclosed that the cause of biliary
      obstruction was a portal cavernoma. In addition, large esophageal varices with
      "red spots" were observed at endoscopy. Propranolol and ursodeoxicolic acid were
      started and the patient has remained asymptomatic to date. The biliary features
      of portal cavernoma are reviewed, as well as its pathogenesis, diagnosis and
      management. Portal cavernoma should be considered in the differential diagnosis
      of chronic cholestasis.

PMID- 9633182
TI  - [New concepts of hospitalization for non-variceal upper digestive hemorrhage].

PMID- 9633183
TI  - [New treatments of hepatic encephalopathy].

PMID- 9633184
TI  - [Treatment of Helicobacter pylori infections].

PMID- 9633185
TI  - [Splenic abscess after prostatic adenomectomy].

PMID- 9633186
TI  - [Polyarteritis nodosa of the gallbladder].

PMID- 9633187
TI  - [Effect of the nootropic agent cerebrolysin in cerebral ischemia in rats with
      varying behavioral reactions in the open field test].
AB  - Open field tests were made on 489 white male rats to distinguish subgroups by
      baseline higher nervous activity (HNA) to study the effects of cerebrolysin
      (EBEVE, Austria) on relationships between neuronal activity and cerebral blood
      supply in normal cerebral circulation (CC) and in acute brain ischemia. Local CC
      and EEG were measured by laser doppler flowmeter and read from the same point
      gauge. CC/EEG index was calculated. Cerebrolysin was injected i.p. in a dose 0.3
      ml/100 g body mass. Brain ischemia was provoked by occlusion of the common
      carotid arteries. Neurological symptoms were estimated according to the McGrow
      scale. Also, 24-h lethality was registered. It was confirmed that cerebrolysin,
      as an active nootrop, enhances EEG. This effect takes place both in intact and
      brain ischemia rats. It was also found that cerebrolysin has different
      effectiveness dependent on the animal's behavior in the open field test, that
      blood supply to the brain does not increase in cerebrolysin-activated HNA. In
      stable circulation, this was compensated due to cerebral metabolic reserve, but
      in intensive EEG activation, recorded by CC/EEG index, cerebrolysin reduces
      cerebral blood supply aggravating acute brain ischemia.

PMID- 9633188
TI  - [Behavioral and morphologic disorders caused by bilateral photoinduced thrombosis
      of the cerebral vessels of the frontal cortex in rats].
AB  - Chronic experiments were made on 35 non-inbred male rats (200-250 g b.w.) to
      study functional and morphological consequences of photochemical thrombosis of
      frontal cortex vessels Defects in CNS function were assessed by conditioned
      reflexes of passive avoidance and behavior in open field tests. The size of the
      ischemic focus and perifocal lesion were measured on the stained histological
      sections. Correction of the postischemic impairment was done by intraperitoneal
      injection of a new nootrop--ethyl ether of N-phenylacetylprolylglycine (GVS-111)-
      in a dose 0.8 mg/kg/day. The results of the experiments show a significant
      neuroprotective and nootropic action of GVS-111 in focal ischemic brain damage.

PMID- 9633189
TI  - [Comparative analysis of the action of antibodies to dopamine and serotonin on
      the functional activity of T- and B-lymphocytes and peritoneal macrophages].
AB  - As shown in experiments on mice C57B1/6, systemic intraperitoneal injection of
      serotonin antibodies in a dose 25 mg/kg or their introduction into cell culture
      in a dose 10(-7)M attenuates proliferative response of lymphocytes on PWM-induced
      stimulation, while functional activity of macrophages is stimulated. Antibodies
      to dopamine neither in systemic nor in cell culture introduction cause noticeable
      changes in lymphocytes proliferative response to their PWM and ConA mitogen
      stimulation. Phagocytic activity of peritoneal macrophages was also unchanged.

PMID- 9633190
TI  - [Effect of verapamil on the activity of Ca2+-, Mg2+-dependent endonucleases in
      hypothalamic cell nuclei in long-term hypovolemic shock].
AB  - Experiments on anesthetized non-inbred 8-17 kg b.w.dogs have demonstrated that
      cerebral ischemia consequent to 4-hour hypovolemic shock activates Ca(2+)-,
      Mg(2+)-dependent endonucleases in cell nuclei of the hypothalamus. Intravenous
      injection of calcium channels blocker verapamil (Orion) in a dose 0.1 mg/kg 30
      min before blood loss prevents activation of the above endonucleases and makes it
      possible to avoid internucleosome fragmentation of genome DNA.

PMID- 9633191
TI  - [Lipid composition of the hypothalamus and hippocampus in sudden cardiac death].
AB  - The study was made of hypothalamic and hippocampal lipid composition in sudden
      death of ischemic heart disease. Biochemical findings rest on the evidence
      obtained at thin-layer chromatography. Lipid disorders of the hippocampal cell
      structures were primarily related to cholesterol fractures. Hippocampal
      metabolism was impaired in phospholipids metabolism. These biochemical changes
      entailed changes in ultrastructure which may represent one of the central
      mechanisms of a sudden cardiac death.

PMID- 9633192
TI  - [Effect of electric stimulation of the cerebral cortex on cardiac nociceptive
      signal conduction].
AB  - In acute experiments on cats we studied the influence of the cortex cerebri
      electric stimulation on potentials in the subcortical structures such as the
      thalamus, hypothalamus, striatum griseum superficiale. The potentials were
      provoked by electric irritation of the nodus synuatrialis zone of the heart
      conducting system. A cortex cerebri depressing effect (mainly the 1st and 2nd
      zones of somatovisceral sensitivity) on cardiac afferent signals with nociceptive
      component was determined.

PMID- 9633193
TI  - [Biogenic amines in rat brain structures in an adjuvant arthritis model].
AB  - The role of changes in biogenic amines neurochemistry in cerebral structures in
      abnormal immunoreactivity accompanying development of autoimmune disease was
      investigated in experiments on 24 Wistar male rats. Biogenic amines and their
      metabolites (dopamine, dioxyphenylacetic acid, serotonin, oxyindolacetic acid)
      were assays in the sensomotor cortex, hypothalamus and hippocamp by means of high
      performance liquid chromatography. Development of adjuvant arthritis was
      associated with definite neurochemical changes in the brain: inhibition of
      serotonin metabolism and enhancement of dopaminergic systems in the hypothalamus
      and sensomotor cortex. Prophylactic administration of oil solution D,L-alpha
      tocopherol acetate promoted enhancement of serotonin metabolism in hypothalamic
      and hippocampal neurons. Bitemporal exposure to UHF electric field aroused
      stronger effects on the neurochemical metabolism in hypothalamic, hippocampal and
      sensomotor cortex neurons than TPA. It is concluded that bitemporal exposure to
      UHF electric field and antioxidant activate central immunoreactivity mechanisms
      in animals with adjuvant arthritis. Serotonin and dopamine systems in this
      process are leading.

PMID- 9633194
TI  - [Effect on cardiac function of altered adenosine metabolism in rat brain
      structures in modelled hyperuricemia].
AB  - Experiments on 24 Wistar male rats were performed to clarify the role of central
      mechanisms in the onset of electrical instability of the heart due to
      disturbances in purine metabolism. The activity of the enzymes responsible for
      synthesis and conversion of adenosine-5-nucleotidase and adenosine deaminase in
      the sensomotor cortex, hypothalamus and hippocamp was studied. Changes in cardiac
      function were most severe in high levels of adenosine in the neurons of the
      sensomotor cortex, hypothalamus and hippocamp. Minimal changes occurred in low
      content of adenosine in the hypothalamus and hippocamp.

PMID- 9633195
TI  - [Principles of functioning of various systems of the human body in the post
      aggressive period].
AB  - The authors' investigations provide the conclusion that in a post-aggressive
      period there are organized cyclic fluctuations in the body hormones,
      penetrability of vessels, electrolytes and blood cells. The cycle takes 48 hours.

PMID- 9633196
TI  - [Effect of chemical sympathectomy on the processes of postnatal axon
      myelination].
AB  - Ultrastructural and morphometric analysis has proved the role of sympathetic
      innervation in postnatal myelinization of motor nerve axons. Sympathectomy in
      early postnatal period of rats inhibits myelinization. This affects structure of
      effectors and neuromuscular contacts.

PMID- 9633197
TI  - [Cardiovascular system in rats with varying resistance to acute hemorrhage].
AB  - Ultrasonic and laser doppler flowmetry, biomicroscopy were used in the study of
      systemic hemodynamics, microcirculation, blood flow in the brain, liver, kidneys
      and inferior limb in rats varying by resistance to acute blood loss. In the
      course of bleeding both high- and low-resistant rats (HRR, LRR) had the same
      decline in blood pressure, blood flow rate and tissue perfusion. When blood loss
      stopped. HRR developed relative compensation of the above parameters followed by
      irreversible fall. Posthemorrhagic recovery of these hemodynamic parameters in
      LRR was not observed. All the LRR showed persistent generalized constriction of
      hepatic, intestinal and renal microcirculation. Pumping performance of the heart
      continued to death in all HRR and in 65% of LRR. After stop of hemorrhage, 35% of
      LRR developed minor cardiac ejection syndrome which was followed by death within
      30 min.

PMID- 9633198
TI  - [Secretory activity of atrial cardiomyocytes in adrenaline myocardiodystrophy].
AB  - Ultrastructure of atrial cardiomyocytes in adrenalin myocardiodystrophy was
      studied in white rat experiments. Morphometrically, there was a reduced number of
      mitochondria and secretory granules in the atrial muscular cells, space
      characteristics of cardiomyocytes and their nuclei increased. The above
      rearrangement of the atrial cardiomyocytes indicates that adrenalin
      myocardiodystrophy is associated with a decline in synthetic and secretory
      function of the test cardiac muscular cells.

PMID- 9633199
TI  - [Apoptosis. Nature of the phenomenon and its role in the intact organism].

PMID- 9633200
TI  - [Gaba-ergic mechanisms of respiratory rhythm disorders].

PMID- 9633201
TI  - [Prevention of blindness in diabetic retinopathy].

PMID- 9633202
TI  - [Study of the efficiency of a non-mydriatic retinal camera in the diagnosis of
      diabetic retinopathy].
AB  - Diabetic retinopathy is one of the most important causes of blindness. Diabetic
      patients do not attend outpatient clinics with the necessary regularity for an
      early diagnosis of the most severe forms of retinopathy. A program was planned to
      compare the efficiency of a 45 degrees non-mydriatic retinal camera with a
      Polaroid instant film versus biomicroscopy with a 78D lens and reverse image
      ophthalmoscope (standard method) in the diagnosis of the presence and evolutive
      degree of retinopathy. In a cross-sectional epidemiologic study a questionnaire
      was administered to 258 randomly selected diabetic patients, 129 with and 128
      without retinopathy. Information was collected of demographics, visual acuity,
      diabetes and resources used with each method. The eye fundus with the poorest
      visual acuity was examined to determine the presence and evolution of retinopathy
      with the two diagnostic methods. The photographic method had an overall
      sensitivity of 91.1%, a specificity of 89.7% and a level of agreement of 82% with
      the standard method. A cost-effective analysis revealed a decrease of 35.7% in
      the cost per true positive case detected with the photographic methods versus the
      standard method. The 45 degrees non-mydriatic retinal camera had a similar
      efficiency to the standard method used in our setting for the diagnosis of
      diabetic retinopathy, which together with a lower cost per patient renders this
      method advisable for its use in medical settings that usually control for
      potential ophthalmologic complications resulting from diabetes mellitus.

PMID- 9633203
TI  - [Endovascular treatment of abdominal aorta aneurysms using bifurcated
      endoprosthesis].
AB  - OBJECTIVE: To obtain an initial assessment of the implantation technique of
      bifurcated vascular endoprothesis in the treatment of abdominal aorta aneurysms
      (AAA). METHODS: Eleven Vanguard type endoprostheses were implanted in eleven
      patients with infra-renal aortic aneurysm. The technique was performed with
      surgical approach in one femoral artery, and percutaneously in the other. The
      procedure was performed with epidural anesthesia. RESULTS: A technical success-
      i.e., the exclusion of the aneurysm--was obtained in all cases. No technical
      complications occurred during the procedure. Three patients had low degree
      contrast leak in the angiographic control immediately after the procedure. Eight
      patients had low grade fever in the immediate follow-up which resolved with
      medical therapy, two patients had hematomas in the approach sites, one renal
      infarction, one ileus for two days, another one for five days, and three patients
      had lymphatic effusion. During follow-up the patients with leak had to undergo co
      axial endoprosthesis implantation. CONCLUSIONS: It is our view that bifurcated
      vascular endoprostheses offer a valid alternative in the treatment of AAA. The
      procedure can be performed with epidural anesthesia and sedation, with a low rate
      of complications. The long term follow-up and the perfecting of the approach and
      resection systems will ultimately dictate their usefulness in this and other
      vascular conditions.

PMID- 9633204
TI  - [Characteristics of chronic hepatitis C in patients infected by human
      immunodeficiency virus].
AB  - OBJECTIVES: To know the characteristics of chronic hepatitis C in HIV-infected
      patients and whether there are differences compared with HIV-negative patients,
      in order to obtain orientative helpful data for the diagnostic-therapeutic
      decision making, a usually difficult issue in these patients. PATIENTS AND
      METHODS: Sixty patients with criteria of chronic hepatitis C virus (HCV) criteria
      were studied. Thirty-three of these patients were coinfected with HIV. The
      possible associations between the degree of histologic damage and several
      variables wee studied: age, estimated time of evolution of HCV infection,
      transaminases, gammaglobulins, GGT, and alcohol consumption. On the other hand,
      the possible differences regarding the histologic hepatic aggression were
      assessed. An attempt was made to know whether HIV could negatively influence the
      evolution of chronic hepatitis C. RESULTS: A direct relationship was observed
      between hepatic damage, HAI and levels of GOT, GPT, GGT (p < 0.005), and
      gammaglobulins (p < 0.01). The degree of hepatic fibrosis was directly correlated
      with the GGT level (mild fibrosis: 47 +/- 34 U/l; severe fibrosis: 86 +/- 60 U/l)
      (p < 0.05) and the estimated evolution time of infection (p < 0.05). Alcohol
      consumption was associated with the fibrosis degree (p < 0.01). The degree of
      histologic damage was similar in the HIV-positive group (HAI: 8.3 +/- 3.6) and
      HIV-negative patients (HAI: 7.2 +/- 2.8), although the degree of lobular
      involvement was higher in HIV-positive patients (p < 0.05). CONCLUSIONS: Patients
      with chronic hepatitis C and infected with HIV did not have a higher degree of
      hepatic damage than HIV-negative patients. GOT, GPT, and gamma globulin levels,
      as well as a longer evolution time of HCV infection were associated with a higher
      degree of hepatic histologic activity. Alcohol consumption seemed to be
      associated with a poorer course of the liver disease in these patients.

PMID- 9633205
TI  - [Clinical implications of hepatitis C virus genotype in human immunodeficiency
      virus infected patients with chronic liver disease].
AB  - OBJECTIVE: To know the prevalence of viral genotype in patients infected with
      hepatitis C virus (HCV) and coinfected with HIV and evaluate its clinical
      implications. PATIENTS AND METHODS: The genotype of the HVC was studied (INNO
      LiPA HCV II, Imnogenetics, Belgium) in 40 patients coinfected with HIV; from 28
      of these patients histologic data of chronic hepatitis were available. The most
      prevalent genotype was analyzed in this type of patients and its associations
      with different issues: risk behavior, histologic activity of liver disease and
      viremia level (quantitative PCR, Amplicor HCV, Roche Diagnostics). RESULTS:
      Genotype 1 was the most prevalent (55%), and subtype 1a predominated (36.3%). In
      most cases genotypes 1a and 3 were found (65%) and in four cases (10%) there was
      coinfection with two genotypes. The most common risk behavior was parenteral drug
      use (PDU) (34 cases), which might account for the higher prevalence of genotypes
      1 and 3. A mild hepatic histologic activity was most frequently associated with
      genotype 3 compared with genotype 1 (63.6% versus 46.6%). The Knodell histologic
      activity index (HAI) was higher in the four patients with coinfection 1 + 3
      versus the remaining patients (11.2 +/- 2.8 versus 7.8 +/- 3.6). The percentage
      of patients with genotype 1 with a viral load > 10(5) was higher than that of
      patients with genotype 3 (80% versus 7.6% [4]) (p < 0.05); in the two cases with
      subtype 1b viremia levels exceeded this limit. CONCLUSIONS: The prevalent HCV
      genotypes in patients coinfected with HIV in our environment seem to be 1a and 3,
      which is probably associated with the more common high risk behavior of PDU among
      these patients. Genotype 3 seems to be associated with a milder histologic liver
      damage and a lower viral load, and these two characteristics might be related.
      The HCV genotype should be considered in subjects coinfected with HIV to obtain a
      better clinical and prognostic evaluation of the chronic liver disease it causes.

PMID- 9633206
TI  - [Report of 8 cases of dermatomyositis: does association of this entity and
      neoplasms exist?].
AB  - BACKGROUND: To review eight cases of dermatomyositis (DM) and investigate the
      association of DM with cancer and mortality rate in this group of patients.
      MATERIALS AND METHODS: Retrospective study of DM cases at Fundacion Jimenez Diaz
      from January 1991 and March 1996. RESULTS: Only two out of the eight patients
      with DM had concomitant carcinomas (undifferentiated medium cell lung carcinoma
      and infiltrating ductal carcinoma of the breast). The mean age was 62 years (the
      two patients with carcinoma exceeded this age). As for gender incidence, one of
      the two male patients in this study had cancer, compared with one out of the six
      female patients. The cause of death in the three patients who died was an
      infection and so far none of the two patients with associated cancer has died.
      CONCLUSIONS: Despite our small series, the incidence of cancer in patients with
      DM (25%) is similar to that observed in larger series (15%-30%). All patients
      presented with cutaneous lesions. Only one of them had also hemoptysis and was
      diagnosed of lung cancer. The diagnosis of breast cancer was obtained with a
      control mammography. The mortality rate in these two patients was not higher. The
      incidence of cancer is higher in older DM patients.

PMID- 9633207
TI  - [Interferon treatment of chronic hepatitis C in human immunodeficiency virus
      infected patients].
AB  - OBJECTIVE: To know the efficiency and tolerance of INF therapy for chronic virus
      C hepatitis (HCV) in HIV infected patients compared with non infected patients.
      PATIENTS AND METHODS: INF-alpha was administered to 39 patients with chronic
      hepatitis C virus infection criteria. In 17 cases (43.5%) there was coinfection
      with HIV. Histologic data were available from 30 patients (75%) and also of viral
      load during therapy (Amplicor HCV, Roche Diagnostics) from 8 patients. We
      determined the response at the end of the first two months of therapy (ER), at
      the end of therapy (FR) and after discontinuation (DR) when the transaminase
      level was normalized and viral RNA was not detected in cases when it was
      measured. The response rates to INF were compared between HIV-positive and HIV
      negative patients and the secondary effects observed evaluated, as well as
      tolerance and severity, with a particular emphasis on the CD4 lymphocyte level
      among HIV-positive patients. RESULTS: An ER was obtained in nine HIV-positive
      patients (52.9%) and thirteen HIV-negative patients (59%); an FR in eight HIV
      positive patients (47%) and eleven HIV-negative patients (50%), and DR in two HIV
      positive patients (13.3%) and four HIV-negative patients (28%); although a lower
      rate of DR was observed among HIV-positive patients, these differences were not
      significant. The disappearance of HCV ARN at the end of therapy was similar for
      both groups of patients in whom it was measured: five HIV-positive patients
      (62.5%) and twelve HIV-negative patients (63.1%). We must consider that HIV
      positive patients had a higher number of poor response predictors to INF.
      Secondary reactions were observed in a higher number of HIV-negative patients
      (81.8% versus 40.9%) and the level of CD4 lymphocytes was markedly reduced during
      and after therapy in three patients. CONCLUSION: INF therapy in chronic hepatitis
      C virus infection in HIV-positive patients initially has a similar efficiency to
      that observed in HIV-negative patients, although perhaps the maintained response
      rate is lower. A higher number of secondary reactions among HIV-positive patients
      was not observed, although possible reductions in CD4 levels must be considered
      among these patients. The use of INF in these patients --if properly selected--is
      therefore not contraindicated.

PMID- 9633208
TI  - [Neurologic diseases associated with alcoholism].

PMID- 9633209
TI  - [Treatment of recurrent aphthous stomatitis. A bibliographic review].

PMID- 9633210
TI  - [Coinfection by human immunodeficiency virus and hepatitis C virus].

PMID- 9633211
TI  - [Alcoholic patient with neuropsychiatric and gait impairment].

PMID- 9633213
TI  - [Hyperkeratotic infiltrated plaques on the dorsum of the hand].

PMID- 9633212
TI  - [Headache and gastric carcinoma].

PMID- 9633214
TI  - [Miction-triggered headache].

PMID- 9633215
TI  - [A 66-year-old man with impaired gait and paresthesias of the lower limbs].

PMID- 9633216
TI  - [Bilateral ischemic optic neuropathy in a diabetic patient].

PMID- 9633217
TI  - [Subacute paraneoplastic cerebellar degeneration in a patient with renal
      adenocarcinoma].

PMID- 9633218
TI  - [Cardiovascular changes during alpha-2 agonist treatment of opiate withdrawal
      syndrome].

PMID- 9633219
TI  - [Multidrug-resistant tuberculosis caused by M. bovis in a patient with human
      immunodeficiency virus infection].

PMID- 9633220
TI  - [Altitude leukonychia].

PMID- 9633221
TI  - [Cerebral venous thrombosis in Behcet's disease: manifestation despite
      anticoagulant treatment].

PMID- 9633222
TI  - [Spiral computerized tomography and 4D reconstruction of the tracheobronchial
      tree: possibilities of the "bronchographic perspective" in bronchial cancer].

PMID- 9633223
TI  - [Tattooing and dyssocial behavior].
AB  - After a brief culturo-historical introduction into the subject of tattooing, the
      author makes a comparison between two groups of offenders with antisocial traits,
      of which only one group consists of tattooed individuals. 48 characteristics
      concerning family history, personal biography, social situation, drug consumption
      habits and clinical aspects are taken into consideration. In general view, it
      shows, that there are very few significant differences between the two groups
      except for the fact, that the tattooed individuals are less characterized by a
      positive family history for delinquency, broken home situations and lack of a
      steady partner. Moreover, there is a tendency for higher education and better
      professional accomplishments in this group. So the question remains, whether
      tattoos could also be considered under the aspect of subcultural status symbols.

PMID- 9633224
TI  - [Conservative medical treatment of chronic pancreatitis].
AB  - The conservative medical treatment of chronic pancreatitis entails dealing
      prevalently with exocrine and endocrine insufficiency, diet and pain. As
      steatorrhoea can cause malabsorption, it is advisable to reduce first the fat
      content of the diet and secondly to prescribe, where necessary, pancreatic
      enzymes. Several factors can lead to a poor therapeutic enzyme effect. Attention
      should be given to the pharmacological properties of the enzyme-preparation and
      to the secretion of acid in the stomach. An endocrine insufficiency is more
      difficult to treat compared to a classical diabetes mellitus, for lack of
      endocrine regulatory mechanisms. Pain is the consequence of several
      pathophysiological processes. Before initiating analgetic treatment, a minimal
      diagnostic program should be completed allowing the exclusion of those primary
      causes of pain which require an alternative approach such as interventional
      endoscopy or surgery.

PMID- 9633225
TI  - [Hypertonic-hyperoncotic solutions: possibilities and limits].
AB  - Hypertonic-hyperoncotic solutions are a supplementary possibility in the acute
      treatment of hypovolemia. The main mechanism of action of this solution is,
      induced by the tonicity of the infusion (approximately 2400 mOsm/l), the
      transcapillary fluid shift from the intracellular and interstitial to the
      intravascular compartment. Additionally the fluidity of blood is improved (due to
      an increase in the diameter of the capillaries), the adherence of leucocytes to
      the endothelial wall is reduced, and the arteriolar vasomotion is restarted. Due
      to the available prehospital and clinical results it can be concluded, that
      hypertonic-hyperoncotic solutions offer advantages compared to conventional fluid
      therapy regimes: rapid stabilization of hemodynamics, reduction of posttraumatic
      volume deficiency, of posttraumatic edema and of posttraumatic complications and
      an improvement of the outcome of the patients. If the therapeutic recommendations
      are followed, such as a dose of 4 ml/kg body weight, infusion time of about 3-5
      minutes and after the end of the infusion application of colloids or crystalloids
      in an amount as needed, no side effects will occur. Only immediately after the
      end of infusion sodium, chloride and osmolarity will slightly increase, however
      these parameters will normalize within the first posttraumatic day. Hypertonic
      hyperoncotic solutions are trigger-solutions, as with the infusion of these types
      of solution it is possible to restore hemodynamics adequately and to prevent
      shock-induced complications.

PMID- 9633226
TI  - [Chylothorax as the initial manifestation of malignant Hodgkin lymphoma].
AB  - A 22 year-old man complaining of slight thoracic pain, was found to have a right
      pleural effusion in his chest X-ray. The pleural aspiration yielded chylous fluid
      and radiological examination and biopsy of a mediastinal mass led to the
      diagnosis of Hodgkin's disease of the nodular sclerosis type with supra- and
      radiologically infradiaphragmatic disease and a pathological fracture of the
      sternum. After complete initial aspiration of the pleural effusion the
      chylothorax did not recur following initiation of a combination chemotherapy, and
      a clear regression of the lymphoma was found after the first 3 cycles. This case
      provides an example of an oligosymptomatic, right sided chylothorax as the first
      manifestation of Hodgkin's disease in a young immuno-competent patient.

PMID- 9633227
TI  - [Respiratory insufficiency and absent left radial pulse after hemicolectomy].
AB  - A 65 year old female developed right thoracic pain, productive cough and fever
      four weeks after hemicolectomy because of a cancer of the sigmoid. In spite of
      antibiotic treatment the condition of the patient deteriorated and she was
      admitted to the hospital with pneumonia of an upper lobe. Chest X-ray visualized
      prominent proximal pulmonary arteries. Progressive respiratory failure developed
      and blood gas analysis revealed hypocapnic hypoxemia. The patient had to be
      intubated and ventilated mechanically. Later, left arm blood pressure
      measurements could no longer be taken and the radial pulse was missing.
      Thereafter, an ischemic syndrome of the right leg developed. Embolectomy from the
      superficial femoral artery was carried out the same day. The patient died five
      days later. Autopsy revealed an almost complete occlusion of the pulmonary
      arteries. The organization of thrombotic material indicated recurrence. Emboli
      were also found in the systemic circulation. A large patent foramen ovale
      together with signs of pulmonary arterial hypertension are indicative of
      paradoxical thromboembolism.

PMID- 9633228
TI  - [Brief psychotherapy versus general practice management--on the efficacy of
      treatment and patient satisfaction].

PMID- 9633229
TI  - [Exanthema in multiple therapy in HIV infection].

PMID- 9633230
TI  - [Skin infiltration in malignant lymphoma].

PMID- 9633231
TI  - [Lipoproteins as a specific circulatory transport system].
AB  - In accordance with the systemic approach, each circulatory transport system is
      highly specific and transports an elementary substance from cell to cell in the
      hydrated medium. In the author's opinion, the lipoprotein system has also a
      functional specificity and carries the elementary substance fatty acid in the
      blood stream. A great variety of fatty acids, the individuality of their
      physicochemical properties, great stereochemic differences of saturated and
      polyenic fatty acids make their transport virtually impossible. The steric
      individuality of fatty acids can be reduced if the acids are covalently bonded by
      a matrix as complex lipids. For formation of complex lipids, nature prefers
      esterification of fatty acids with alcohols which have a varying hydrophoby, such
      as glycerol, sphingosine, cholesterol, cetyl alcohol. The steric differences of
      saturated and polyenic fatty acids form a basis for their being structurized in
      different lipids. Triacyl glycerides are a transport form of saturated,
      monounsaturated fatty acids and their transforms and give rise to a crystalline
      phase. Phospholipids and cholesterol esters are a transport form of mainly
      polyunsaturated fatty acids in the polar phase in the former case and in the
      crystalline phase in the latter one. The individual apolipoproteins structure
      complex lipids into individual lipoprotein particles and transport them in the
      hydrated medium of blood flow. Saturated fatty acids chiefly transport
      lipoprotein particles formed by apoB-48- and apoB-100-isoproteins. Polyenic acids
      transport mainly high-density apoA-1-lipoprotein particles, which makes up a main
      physiological function of the latter. Cholesterol is nothing more than a matrix;
      it reesterifies polyenic fatty acids from the polar transport form of
      phospholipids into the unpolar transport form of cholesterol esters. Cholesterol
      esterification of polyenic fatty acids may structure complex lipid in the unpolar
      phase and transport it to the cells via apoB-100-ligand-receptor interaction,
      which is considered to be a key stage in the multistage process of active
      transport to the cells of polyenic fatty acids. However, the significant
      differences of active and inactive transport of polyenic fatty acids in the blood
      stream await a separate consideration.

PMID- 9633232
TI  - [Value of endoscopic studies in prevention and early diagnosis of malignant
      gastrointestinal tumors].

PMID- 9633233
TI  - [Effects of pancreatic polypeptide amylin on ulceration and acid gastric
      secretion].
AB  - The effects of the pancreatic polypeptide amyline on ulceration and acid gastric
      secretion were studied in rat experiments. Pyloric ligation was used as a model
      of ulceration. Amyline administration caused significantly less gastric mucosal
      damage in response to pyloric ligation. The severity of gastric mucosal damage
      averaged 47 +/- 13 mm2 in the control group and 25 +/- 11 mm2 (p < 0.005). The
      rate of acid gastric secretion in the animals whose pylorus had been ligated as
      judged by the pH of gastric content was significantly higher than that in the
      controls (2.87 +/- 0.22 and 2.34 +/- 0.17 (p = 0.05). It is concluded that
      amyline has a noticeable effect on the gastric mucosa. It is suggested that
      suppressed acid gastric secretion, i.e. reduced influence of aggressive agents on
      the gastric mucosa, is a mechanism of antiulcerative action of the peptide.

PMID- 9633234
TI  - [Design of stimulating agents of non-specific resistance system].
AB  - The paper briefly reviews a study on the design of drugs enhancing the body's
      nonspecific resistance to pathogenic agents. To examine the potential regulatory
      effects on cytokine function was a main trend. The interferon inductor ridostin,
      dsRNA of microbiological origin, cytokines, as well as the recombinant probiotic
      strain yielding interferon alpha-2 synthesis were used as a pharmacological
      agent. This was shown by using a wide range of experimental models wherein these
      preparations activated the components of the non-specific resistance system
      resulting in the host's increased capacity to eliminate invasive agents and
      transformed cells.

PMID- 9633235
TI  - [Studying the possibility of respiratory immunization against tick-borne
      encephalitis].
AB  - There are known 3 likely mechanisms of virus conveyance into the central nervous
      system (CNS). These include hematogenic penetration, spread along the peripheral
      nerves, and the olfactory pathway which begins from the infected olfactory
      neuroepithelial cells. The possibility of viral spread into CNS via the olfactory
      pathway was shown for the representatives of togaviruses, herpesviruses,
      coronaviruses, rhabdoviruses, and for some others. This study suggests that the
      olfactory pathway of viral conveyance into CNS may be blocked by specific mucosal
      antibodies in the nasal mucosa. The recombinant TK- variant of WR vaccinia strain
      with inserted genes coding structural and nonstructural proteins of TBE virus is
      accumulated in the branches of the respiratory tract only while the parenteral
      vaccinia strain is detected in the brain regions, spleen, respiratory tract, and
      in blood. The protective activity of recombinant strain and inactivated TBE
      vaccine after mice immunization by escarification or intranasally, or
      subcutaneously was comparatively studied. The findings indicate that intranasal
      immunization by recombinant strain is the most protective against intraperitoneal
      challenge by TBE virus. The mucosal and humoral immune response that was induced
      by intranasal immunization seems to provide the highest levels of protection,
      which was experimentally observed.

PMID- 9633236
TI  - [Human herpesvirus-6 (HHV-6): current status].
AB  - Molecular, biological, and immunological studies on the recently identified human
      herpesvirus-6 (HHV-6) suggest that the virus is involved in the etiology of at
      least several lymphoproliferative diseases. Furthermore, HHV-6 may be an
      important cofactor in the pathogenesis of several other diseases, including
      cervical carcinoma, oral carcinoma, multiple sclerosis, and HIV infection.
      Analyzing the data available in the literature shows it necessary to conduct
      systematic investigations and to emphasize the importance of the problem for
      national public health.

PMID- 9633237
TI  - [Developing methods of specific heterologic immunoglobulins preparation for
      urgent prevention of Ebola fever and study of their properties].
AB  - Methods for preventing and treating Ebola virus hemorrhagic fever are not still
      available despite the fact that this virus have been studied for 20 years.
      Methods of immunization of the animals (sheep, goats) non-susceptible to Ebola
      virus with live virus preparations were developed to obtain the hyperimmune anti
      Ebola virus sera required to have highly immune antivirus gamma-globulins. These
      methods made it possible to obtain the immune sera having high virus-neutralizing
      antibodies. Caprine immunoglobulins were obtained from sera by fractionation of
      immune sera by Kohn's method. The neutralization indices of the immunoglobulins
      obtained were at least Ig. When administered in the first hours of infection, the
      protective effect of these preparations was shown on guinea pigs infected with
      LD50 of the strain pathogenic to the animals. Preclinical trials of these
      immunoglobulins on laboratory animals and clinical trials on volunteers were
      performed. The preparation was used as a preventive agent when accidents took
      place at the laboratory working with Ebola virus. The similar preparation from
      equine sera having high neutralizing and protective properties was elaborated at
      the Virological Center, Microbiological Institute, Russian Ministry of Defense.
      Its prophylactic efficiency was also shown in infected gamadrias.

PMID- 9633238
TI  - [Polypeptide composition of major antigens and identification of prevalent
      immunogenic proteins of opisthorchis felineus].
AB  - The polypeptide composition of somatic, excretory-secretory, and egg antigens of
      the liver trematode Opisthorchis felineus has been investigated by SDS
      electrophoresis. All three main antigens consist of a large number of different
      polypeptides and have original electrophoretic profiles. The first original
      classification of the main polypeptides of somatic, excretory-secretory, and egg
      antigens of O. felineus is proposed. Immunoblotting showed that serum antibodies
      fail to recognize all polypeptides. The human serum antibodies mainly interacted
      with protein p105 alone. The restricted human immune response can be critical to
      further development of immunoassay for opisthorchiasis. Eighteen monoclonal
      antibodies against O. felineus p105 were obtained and their main properties were
      examined. Furthermore, this will improve immunoassay and investigation of the
      mechanisms responsible for immune response to O. felineus antigens.

PMID- 9633239
TI  - [Some aspects of interferon formation in white mice].
AB  - White mice weighing 14-16 g were intranasally infected with LD50 of influenza
      virus (A/Aichi/2/68 strain). High levels both of virus and interferon were
      detected in the lung. Sufficient virus accumulation in the nasal cavity occurred
      with low interferon induction. At the same time high blood interferon levels
      corresponded to sporadic low viremia. Intraperitoneal injection of the interferon
      inducer ridostin (a pharmacological formulation of dsRNA) to BALB/c mice (18-20
      g) in a dose of 5 mg/kg induced intensive blood accumulation of interferon with
      its peak at 8 hours postadministration (2560 U/0.2 ml), but interferon was not
      detected in the respiratory tract and brain of these mice. Intranasal (15 mg/kg)
      and aerogenic (0.4-0.6 mg/kg) administration of ridostin induced interferon
      mainly in the upper respiratory tract and lung. The regularities found are in
      agreement with the data on interferon induction by other dsRNA preparations,
      which makes it necessary to design dosage forms of interferon inducers for
      respiratory application in influenza.

PMID- 9633240
TI  - [Clinical and epidemiological aspects of infectious diseases (findings from Saint
      Petersburg)].
AB  - The paper analyzes official statistics on infectious diseases, data on the course
      and outcomes of infections which have been most common in the region in the past
      20 years. It shows that the epidemiological situation has deteriorated, the
      incidence of severe and complicated forms and mortality due to infectious
      diseases have increased. Great emphasis is laid on the epidemics of dysenteria
      and diphtheria in the past years. The etiological, clinical and epidemiological
      features of acute viral hepatitis are discussed. The HIV infection situation is
      assessed. The paper shows it necessary to improve outpatient diagnosis of
      infections, to rigorously implement a programme for vaccine prevention, to
      develop adequate etiotropic and pathogenetic therapeutic techniques for
      infectious diseases.

PMID- 9633241
TI  - [Electrophysiological criteria for efficacy of different antiarrhythmics classes
      in patients with paroxysmal reciprocal atrioventricular nodal tachycardia].
AB  - Clinical and electrophysiological studies of 510 patients with different
      paroxysmal reciprocal atrioventricular nodal tachycardias identified criteria for
      resistance of paroxysmal nodal tachycardia. Examination of changes in major
      electrophysiological parameters due to different antiarrhythmics established the
      specific features of their electrophysiological action and thereof criteria for
      the efficacy of antiarrhythmic therapy.

PMID- 9633242
TI  - [Development of pediatric surgery in Leningrad-Saint Petersburg].

PMID- 9633243
TI  - [Experimental study of therapeutical properties and safety of king crab
      collagenase-containing ointment].
AB  - The effects of ointment containing king crab (Paralithodes camtschatica)
      collagenase on intact skin, thermal, and pyonecrotic wounds were studied in rats
      by using hematological, biochemical, immunological, and morphological methods.
      The ointment for the skin and viscera was shown to be safe. It is highly
      effective in debriding the infected wounds. Different concentrations of
      collagenase were tested. The concentration of collagenase was recommended to be
      0.2 mg/g ointment for use.

PMID- 9633244
TI  - [Topical problems of hygienic certification of computers].
AB  - The paper provides evidence that while making a hygienic certification of
      computers it is necessary to rely not only on their physical and technical data,
      but on the characteristics obtained by defining the integral physiological
      parameters of the quality of displayed information perception. According the
      state standards CaH [symbol: see text] 2.2.2.54-96, their hygienic certification
      requires differential assessment of computers with the age-specific features of
      users (pre-school and young school children, middle- and old-aged schoolchildren,
      adults). It is proposed that CaH [symbol: see text] 2.2.2.54-96 should be
      supplemented by a regulation on choice of special working places with appropriate
      protective devices for the children of a risk group.

PMID- 9633245
TI  - [Crisis of health and health care as a threat to the country's national
      security].

PMID- 9633246
TI  - [The management of military medical service as a scientific and academic
      discipline].
AB  - Scientific generalization of the medical units maintenance experience in wars and
      armed conflicts of the second half of the XX century and at occurrence and
      liquidation of consequences of the extreme situations in view of further
      development of the military--medical science, its differentiation and formation
      of new scientific disciplines and theories. Justified necessity for medical
      service management theory in a relatively independent branch of the military
      medical service--medical science. The distinctive attributes of the scientific
      discipline are indicated. The definitions and the structure of the object and the
      subject of the theory of management of the medical service are given, and new
      laws are formulated. The purpose, problem and contents of management of the
      medical service as educational discipline is determined. Some questions of
      coordination of its fundamental and applied parts are discussed.

PMID- 9633247
TI  - [Means for improving the medical evacuation of the wounded and sick].

PMID- 9633248
TI  - [Agents for large-volume fire fighting in personnel living quarters].

PMID- 9633249
TI  - [Oxygen support of the regimental medical service].

PMID- 9633250
TI  - [The potentials of molecular genetic diagnosis in military medicine (a review of
      the literature)].
AB  - The practical importance of the main genetic infringements in diagnostics of a
      wide circle of illnesses, including cardiology, nephrology, and oncology. Methods
      used. The exclusive effectiveness of application of the polymerasic chain
      reaction in the purposes of diagnostic. Expediency of application of the
      molecular-genetic methods for radiating, chemical and extreme effects evaluation.

PMID- 9633251
TI  - [Qualified surgical care in gunshot wounds of the pelvis].

PMID- 9633252
TI  - [Initial experience with using the EC-5000 Nidek laser in military
      ophthalmology].

PMID- 9633253
TI  - [The complex assessment of the adaptive reactions of patients at the sanatorium
      stage of rehabilitation after reconstructive heart operations].

PMID- 9633254
TI  - [Disorders of the cognitive functions in those who worked in the cleanup of the
      aftermath of the accident at the Chernobyl Atomic Electric Power Station].

PMID- 9633255
TI  - [The etiopathogenetic therapy of acute pain syndromes located in the lumbosacral
      area].

PMID- 9633256
TI  - [Aurorix--an antidepressant with a wide spectrum of action].

PMID- 9633257
TI  - [The clinical and morphological characteristics of the internal organ lesions in
      diphtheria with a fatal outcome].

PMID- 9633258
TI  - [The systems of prophylactic and ecological support for the Armed Forces: their
      status and interrelationships].
AB  - In the article the theoretical bases of preventive and ecological maintenance of
      the armed forces are discussed. It is specified, that the main reason for
      preventive maintenance is preservation and strengthening of health and
      performance of the personnel, and for the ecological maintenance-achievement of
      ecological safety: preservation and restoration of the environment. As a result,
      protection of the personnel from the effect of the adverse factors is offered as
      a sub-gain of the ecological maintenance, and a sub-gain of preventive
      maintenance is the control of the environment protection, which defines the
      health state of the personnel.

PMID- 9633259
TI  - [Mobile medical units for northern regions].

PMID- 9633260
TI  - [Military medical trauma expertise and insurance for servicemen].

PMID- 9633261
TI  - [Non-combat health losses in the Soviet Armed Forces].

PMID- 9633262
TI  - [The current procedure for the surgical treatment of combat gunshot eye
      injuries].

PMID- 9633263
TI  - Urbanization, mental health, and social deviancy. A review of issues and
      research.
AB  - This article reviews the international research literature on the relationship of
      urbanization, mental health, and social deviancy. Attention is called to the
      multidisciplinary and multisectoral nature of the topic, and to its associated
      definitional, conceptual, and methodological issues and challenges. Selected
      research literature on rural-urban differences in mental health and social
      deviancy is reviewed. There is little consensus on the causal relationship
      between urbanization, mental health, and social deviancy, although numerous
      environmental and social pathogenic processes have been posited and investigated.
      Data indicate rural and urban milieus can have both pernicious and salutary
      consequences and that more research is needed to specify critical etiological
      factors and their relationship to subpopulation characteristics. Suggestions for
      improving future research efforts are offered, including the use of more complex
      theoretical models, measurement indices, and data analysis procedures.

PMID- 9633264
TI  - Children in low-income, urban settings. Interventions to promote mental health
      and well-being.
AB  - Urbanization provides unique political, cultural, economic, and educational
      opportunities for children and families. However, it may also have a negative
      impact on the mental health and well-being of children and adolescents,
      particularly when they are exposed to settings with high rates of crime,
      violence, delinquency, substance use, abuse, and poverty. Psychologists are well
      suited to intervene in problems associated with urbanization. However, most
      psychological services have been directed toward children who are experiencing
      problems, and there has been less focus on population-based or preemptive
      interventions that prevent problems before they occur. This review presents 11
      recommendations for urban interventions that build on individual, family, and
      community strengths to promote the mental health and well-being of urban children
      and adolescents.

PMID- 9633265
TI  - Urban neighborhoods and mental health. Psychological contributions to
      understanding toxicity, resilience, and interventions.
AB  - The psychological consequences of living in urban neighborhoods are described by
      using examples related to 3 models of neighborhood characteristics. These models
      highlight the impact of physical, structural, and social characteristics on
      various types of mental health outcomes. In addition, the characteristics of
      individuals and neighborhoods that encourage resilience to negative outcomes are
      discussed. Finally, examples of how psychology can contribute to neighborhood
      interventions that ameliorate or prevent residents' distress and improve
      neighborhood conditions are described.

PMID- 9633266
TI  - The Agency for Health Care Policy and Research Smoking Cessation Clinical
      Practice Guideline. Findings and implications for psychologists.
AB  - Smoking is the leading cause of preventable morbidity and mortality in the United
      States, and the health benefits of quitting smoking are substantial.
      Nevertheless, over 25% of American adults (48 million individuals) continue to
      smoke, and the vast majority of quit attempts are unsuccessful. The Agency for
      Health Care Policy and Research recently addressed the smoking problem by
      conducting a 2-year research project that was published as the Smoking Cessation
      Clinical Practice Guideline (Fiore et al., 1996). This article reviews methods,
      analyses, and results from the Guideline project, and highlights major Guideline
      recommendations. Guideline findings and recommendations are discussed with
      respect to their implications for psychology.

PMID- 9633267
TI  - Puff the magic dragon: how our understanding of fallout, residual and induced
      radiation evolved over fifty years of nuclear weapons testing.
AB  - Radiobiological science has proceeded on empirical principles since health
      physics became a necessary professional adjunct to the military and civilian uses
      of nuclear energy in the aftermath of the detonations at Hiroshima and Nagasaki.
      This paper reviews the data which gradually emerged indicating that early
      assumptions about the detonation of atomic and nuclear weapons underestimated the
      significance of fallout, residual and induced radiation as health hazards. Many
      of these assumptions are being examined in three test cases concerning veterans
      of United Kingdom atomic and nuclear weapons tests heard by the European Court of
      Human Rights in November 1997.

PMID- 9633268
TI  - Surviving the impossible: the long march from Srebrenica. An investigation of the
      possible use of chemical warfare agents.
AB  - In July 1995 about 15,000 people attempted to walk from the enclave of Srebrenica
      to free territory in Bosnia. Two-thirds were captured or killed. Many of the
      remainder experienced hallucinations on the march, leading them to believe they
      were the victims of chemical weapons. This paper reports extended structured
      interviews with 35 survivors, including three doctors, carried out a year later
      on behalf of Human Right Watch. The literature on the likeliest CW agent, 3
      quinuclidinyl benzilate (BZ), and on stress as a cause of hallucinations, is
      reviewed. While CW exposure cannot be ruled out, it is concluded that the
      hallucinations can be ascribed to the consequence of multiple stresses--artillery
      attacks, exhaustion due to lack of sleep, starvation, thirst and the effects of
      drinking unpurified water.

PMID- 9633269
TI  - Gulf War illnesses: complex medical, scientific and political paradox.
AB  - Gulf War illnesses are a collection of disorders that for the most part can be
      diagnosed and treated, if effective programmes exist to assist veterans, and in
      some cases their immediate family members. Although these illnesses are complex
      and have multi-organ signs and symptoms, a proportion of these patients can be
      identified as having Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME)
      and/or Fibromyalgia Syndrome (FMS). Although there are many possible causes of
      CSF/ME/FMS, chronic infections can explain, at least in a subset of patients, the
      apparent transmission of these illnesses to family members and the appearance of
      chronic, multi-organ and auto-immune signs and symptoms. Unfortunately, many
      veterans who have been diagnosed with chronic infections, such as mycoplasmal
      infections, cannot obtain adequate treatment for their condition, resulting in
      their reliance on private physicians and clinics for assistance. This lack of
      response may ultimately be responsible for the transmission of the illness to non
      veterans.

PMID- 9633270
TI  - Pathophysiology of heart failure update: the role of neurohumoral activation in
      the progression of heart failure.
AB  - Understanding the pathophysiologic mechanisms responsible for producing heart
      failure is necessary before effective treatments can be developed that increase
      survival and improve quality of life. Recent advances in the treatment of heart
      failure can be traced directly to improved appreciation of the role of
      neurohumoral activation in the pathophysiology of heart failure. Initially
      adaptive, neurohumoral activation ultimately results in a series of
      overadjustments that actively participate in the progression of heart failure. In
      this article, the role of neurohumoral activation, ventricular remodeling, and
      various peripheral vascular abnormalities in the pathophysiology of heart failure
      are explored.

PMID- 9633271
TI  - Innovations in the pharmacologic management of heart failure.
AB  - Improved understanding of the pathophysiologic course of heart failure has led to
      many advances in pharmacologic therapy. Angiotensin-converting enzyme inhibitors
      represent the first effort at targeting neurohormonal activation in chronic heart
      failure. More recently, beta-adrenergic receptor antagonists have been shown
      effective in blocking chronic sympathetic nervous system activation. The roles of
      digoxin and the newer, vasoselective calcium channel blockers in heart failure
      have been better defined. Other agents targeting the neurohormonal system are
      under investigation. These include angiotensin-receptor antagonists, aldosterone
      inhibitors, and endothelin antagonists. Experience with phosphodiesterase
      inhibitors and adrenergic agents has confirmed the importance of neurohormonal
      activation in progression of heart failure. Despite angiotensin-converting enzyme
      inhibitor, diuretic, and digoxin therapy, mortality in heart failure remains
      high. Careful manipulation of the neurohormonal response to heart failure holds
      promise for altering the course of the disease.

PMID- 9633272
TI  - Surgical alternatives in the treatment of heart failure.
AB  - Heart failure continues to plague a large population worldwide, and its incidence
      is increasing annually as a result of an aging population. It is associated with
      lengthy hospital stays, multiple hospital readmissions, and decreased quality of
      life because of its clinical manifestations. Although cardiac transplantation has
      become the therapy of choice for patients with heart failure, scarcity of donor
      hearts and age limitations prohibit its widespread use. Despite major advances in
      medical management, researchers continue to explore alternative surgical
      therapies to help augment cardiac function. This article explores surgical
      interventions in the management of heart failure, many of which are still
      experimental or in clinical trials. Coronary artery bypass surgery, dynamic
      cardiomyoplasty, and partial left ventriculectomy for the management of heart
      failure are discussed in detail. Descriptions of each surgical procedure, special
      care needs, and clinical outcomes are presented. However, because readers are
      familiar with the coronary artery bypass procedure and postoperative patient
      care, the discussion will focus on issues related to coronary artery bypass
      grafting in the presence of ischemic cardiomyopathy.

PMID- 9633273
TI  - Mechanisms and management of ventricular dysrhythmias in heart failure.
AB  - Despite recent pharmacologic and surgical advances in the management of heart
      failure, the morbidity and mortality rates of this chronic illness remain high.
      Ventricular dysrhythmias are common in heart failure and may be independently
      associated with increased mortality rates. Although the risks of sudden cardiac
      death leading to the patient's death are increased by the presence of complex
      ventricular dysrhythmias, the management of dysrhythmias is subject to
      controversy. The purpose of this article is to review the normal
      electrophysiologic properties of the heart and to examine the likely mechanisms,
      diagnostic approaches, and proposed treatments for ventricular dysrhythmias in
      heart failure.

PMID- 9633274
TI  - Exercise training in heart failure: inpatient and outpatient considerations.
AB  - Exercise training has become increasingly important in the treatment of heart
      failure patients. It has long been known that the exercise tolerance of a patient
      with heart failure is related to his or her morbidity and mortality. Recently, it
      has been proved that exercise training improves cardiorespiratory function,
      functional status, and psychosocial status of heart failure patients. It is
      unknown whether these improvements will improve morbidity and mortality but
      quality of life appears to be enhanced. Subtle improvements in these areas may
      lead to a more satisfying and productive life for many heart failure patients.
      However, further investigation of the specific effects of such improvements is
      needed.

PMID- 9633275
TI  - Heart failure: strategies to enhance patient self-management.
AB  - Successful management of heart failure requires an active partnership between the
      patient and health care providers. This can be facilitated through a focused
      patient education plan that begins in acute care and has continuity into the
      community. Elements of the education plan involve both teaching content areas and
      self-management behaviors. Clinical pathways for heart failure incorporate
      teaching and educational strategies to guide the work of the multidisciplinary
      team, and the advanced practice nurse has tremendous potential in facilitating
      improved patient outcomes.

PMID- 9633276
TI  - Management of chronic heart failure in the outpatient.
AB  - Current management of chronic heart failure involves reducing the personal and
      economic burden through controlling symptoms, reducing hospital admissions, and
      slowing the progression of ventricular dysfunction. As healthcare providers
      struggle to control the rising costs of health and illness care while reducing
      morbidity and mortality rates associated with chronic illness, alternative
      practice models must be evaluated. This article describes a collaborative
      practice model designed to improve care of older adults with chronic heart
      failure. Strengths of the model include the use of evidence-based guidelines for
      heart failure management and for organization of the practice.

PMID- 9633277
TI  - Negotiating an acute care nurse practitioner position.
AB  - Acute care nurse practitioners (ACNPs) entering the current job market or
      relocating must be able to sell their personal and professional attributes to
      potential employers. In many areas, health care providers may be unfamiliar with
      the scope of practice and competencies of an ACNP. As a result, ACNPs will be
      required to educate potential employers as they simultaneously negotiate for a
      position. A well-prepared proposal is one tool the ACNP can use to educate the
      health care team and to build a strong base for negotiations. Successful
      negotiations also depend on the attitude projected by the ACNP. An attitude that
      projects an unwavering belief in the value and benefits of the ACNP can enhance
      the negotiator's position and improve the chances for success. Creating the
      proposal and developing attitudes for success can be accomplished through an
      organized process of preparing for negotiations. The purpose of this article is
      to describe the attitude needed for success, the steps in preparing for
      negotiation, and the development of an ACNP proposal.

PMID- 9633278
TI  - Documenting acute care nurse practitioner practice characteristics.
AB  - Acute care nurse practitioners are functioning in a health care system that is
      changing rapidly. Simultaneously, the ACNP role is evolving. It is imperative
      that ACNPs document practice characteristics to communicate effectively within
      the health care system. The purpose of this article is to describe the process of
      documenting ACNP practice. Content includes rationale for documenting ACNP
      practice characteristics, a description of types and sources of data to collect,
      a discussion of barriers to documentation, and a format for a documentation tool.

PMID- 9633279
TI  - Is there a health promotion and protection foundation to the practice of acute
      care nurse practitioners?
AB  - Currently, debate continues regarding defining the role of nurse practitioners in
      the acute care setting. Health maintenance, health promotion, disease prevention,
      and health restoration are central goals of nurse practitioner care. Some
      question the degree (if any) to which acute care nurse practitioners regard
      health promotion as a basis for their practice. In this article, the concept of
      health promotion and protection is explored, with application to patients in the
      acute care setting; and the extent to which acute care nurse practitioners
      support such practices is examined.

PMID- 9633280
TI  - Reports of role descriptions of acute care nurse practitioners.
AB  - Expanded roles and practice settings are evolving for the Acute Care Nurse
      Practitioner (ACNP). In this study, the ACNP's role is described by 384 people
      seeking certification. Although ACNPs continue to work predominantly in tertiary
      care centers, ACNP roles in secondary and other facilities have emerged. Acute
      care nurse practitioners report that managing patient care; providing care
      consistency; interacting with family members; planning for patient discharge; and
      teaching the patient, family, and other members of the health care team are major
      focuses of the role. Changes in health care will continue to give rise to new and
      innovative settings for ACNP practice. Communication about the ACNP remains
      essential to gaining acceptance of the role and enabling its expansion.

PMID- 9633281
TI  - Demonstrating the value of the advanced practice nurse: an evaluation model.
AB  - Advanced practice nurses are challenged to assess comprehensively the value of
      their role and the impact of their practice. Value is defined as quality divided
      by cost. The correlations among the structure, strategies of care (process), and
      their objectives (outcome) are key to the assessment of the quality of care and
      the impact of the advanced practice nurse's role. Advanced practice nurses are
      challenged to provide high quality care for a competitive or decreased cost. For
      the profession of nursing, outcomes are the result of interventions based on the
      nurse's clinical judgment and theoretical, practical, or scientific knowledge. An
      evaluation model is presented that comprehensively measures the impact of
      advanced practice nurses on patients and families, and an example is presented.
      Using the model will give credibility and validity to the APNs' positive impact
      on the quality and financial outcomes of care for each patient and for entire
      patient populations.

PMID- 9633282
TI  - Role of the clinical nurse specialist: an integrative review of the literature.
AB  - This review of the literature related to the role of the clinical nurse
      specialist was commissioned by the AACN in order to provide a comprehensive
      resource for advanced practice nurses. This review provides a historical overview
      of clinical nurse specialists and some of the gaps or barriers to practice that
      have been experienced. A summary of these gaps shows that many have repeated
      themselves over the years. Also provided are potential solutions to facilitate
      the progression of this role in the future.

PMID- 9633283
TI  - New twists for familiar faces.

PMID- 9633284
TI  - HCFA document outlines reimbursement provisions.

PMID- 9633285
TI  - Planning ahead for health problems during a vacation.

PMID- 9633286
TI  - Combining herbal supplements with prescription drugs.

PMID- 9633287
TI  - Wanted: a good night's sleep.

PMID- 9633288
TI  - Cholesterol & atherosclerosis: a controversy resolved.
AB  - We should regard the so-called cholesterol "controversy" as resolved. Elevated
      cholesterol levels cause coronary disease and probably are an essential
      ingredient for the development of atherosclerosis. Elevated cholesterol levels
      should be a cause for concern. From a public health point of view, the ultimate
      treatment of atherosclerosis will depend on major changes in the lifestyles of
      populations in developed countries, including a shift to diets that are largely
      vegetarian, as well as the elimination of tobacco use, an increase in regular
      exercise, and a reduction in the propensity of to increase weight, particularly
      with age. For patients at high risk for coronary events, including those with
      other coronary risk factors and with clinically established coronary disease,
      cholesterol lowering is absolutely essential. In the majority of cases, it will
      require not only dietary change but also cholesterol-lowering medication. Taken
      together, these public health and medical measures can massively reduce, if not
      eliminate, the burden of atherosclerosis that currently plaques developed
      countries and now threatens the developing world.

PMID- 9633289
TI  - Metastatic melanoma. The latest treatment options.

PMID- 9633290
TI  - Double duty. Treating the dual diagnoses of HIV and substance abuse.

PMID- 9633291
TI  - Insulin delivery methods. A review of today's choices.

PMID- 9633292
TI  - Interstitial cystitis. A diagnostic and therapeutic dilemma.

PMID- 9633293
TI  - Is it heart attack, or is it GERD?

PMID- 9633294
TI  - Giving the allergic salute an honorable discharge.

PMID- 9633295
TI  - Multistate licensure.

PMID- 9633296
TI  - Sound advice about stethoscopes.

PMID- 9633297
TI  - Back from the dead. Emerging and re-emerging infectious diseases.

PMID- 9633298
TI  - My changing role.

PMID- 9633299
TI  - Rethinking continuing education.

PMID- 9633300
TI  - Supporting moms.

PMID- 9633301
TI  - Standing up for aspartame.

PMID- 9633302
TI  - Exploring nurses' roles in limited ultrasound.

PMID- 9633303
TI  - Impacting public policy. Fellowships; internships foster nursing leaders.

PMID- 9633304
TI  - Nurses speak out. Are you practicing telehealth?

PMID- 9633305
TI  - Heart-healthy eating.

PMID- 9633306
TI  - Advanced practice nursing. Two NPs reflect on their roles & responsibilities.

PMID- 9633307
TI  - Clinical focus: keeping moms and babies together.

PMID- 9633308
TI  - Childbirth education options. Exploring one-day classes.

PMID- 9633309
TI  - Doulas: exploring their roles with parents, hospitals, & nurses.

PMID- 9633310
TI  - Getting the most for your conference dollars.

PMID- 9633311
TI  - Home birth: bringing its best options to the L&D.

PMID- 9633312
TI  - Attracting and keeping nurses.

PMID- 9633313
TI  - Ski operator says education is key.

PMID- 9633314
TI  - On how to retain experienced RNs.

PMID- 9633315
TI  - Worried about health of health care.

PMID- 9633316
TI  - U.S. may face nurse shortage too.

PMID- 9633317
TI  - Bridging the discharge process.
AB  - Current mental health initiatives are decreasing the number of psychiatric beds
      and thus increasing the number of clients with serious mental illness who are
      being served in the community. Such changes have implications for clients'
      quality of life and health care economics. To implement the changes while
      addressing the unique needs of psychiatric clients, appropriate models of
      discharge planning and community integration are critical.

PMID- 9633318
TI  - Caring practices and the financial bottom line.
AB  - Canadian health care is facing enormous pressures. The provinces are having
      difficulties coping as declining federal support for health care results in
      reduced transfer payments and as lower tax revenues impair governments' ability
      to control deficits. To survive the necessary budget cuts, facilities are
      restructuring and trying new systems of management, such as multiskilling,
      outcome measurement and total quality management. These measures are saving the
      required dollars, but they have put caring at great risk.

PMID- 9633319
TI  - Preparing kids for the new baby.
AB  - Sibling prenatal classes are a natural extension of nursing's interest and
      expertise in childbirth preparation for expectant couples. From parents'
      perspective, these classes have the potential to decrease sibling rivalry and
      facilitate parental coping with older children's concerns about a new baby. From
      a nurse educator's perspective, sibling prenatal classes offer a rich learning
      experience for students by providing an opportunity to integrate knowledge about
      pregnancy and birth with communication skills and child development knowledge.

PMID- 9633320
TI  - Reducing cervical cancer among First Nations women.
AB  - First Nations women in British Columbia have a four to six times higher mortality
      rate from cancer of the cervix than do women in the general population. Their
      participation in the provincial Cervical Cytology Screening Program (CCSP) is
      less regular and less frequent than other women in B.C. Likewise, they have more
      difficulty in obtaining culturally suitable health care services from respectful
      and consistent professionals. These issues should be of critical concern to
      nurses, as nurses provide the majority of health services to First Nations
      people.

PMID- 9633321
TI  - [Health education programs: elements of critiquing].
AB  - Health education programs don't always meet expectations. This article analyzes
      the factors that contribute to their failure, including complexity or
      underutilization of theoretical models, and poor articulation of research.
      Another factor is the disparity in approaches to understanding and intervening in
      the health experiences of the public. The author briefly describes three main
      approaches to health education--the individual, the ecological and the
      interactional--to suggest new avenues for work, deliberation and assessment. Also
      discussed is the need to clarify limits, foundations and objectives of health
      education. Finally, the role of the nurse in practical and research activities is
      examined. These activities are challenging and demanding and require informed,
      determined commitment.

PMID- 9633322
TI  - My home community.

PMID- 9633323
TI  - A passion for justice.

PMID- 9633324
TI  - Top ten reasons to rethink taking that clinical nurse specialist position.

PMID- 9633325
TI  - Here we go again!

PMID- 9633326
TI  - Patients' views of quality of life: transforming the knowledge base of nursing.
AB  - Nurses in advanced practice roles are leaders of the transformative process that
      will further define the discipline of nursing as a human science of lived
      experience. Essential to the transformation is a change in nursing's knowledge
      base, a change that defines practice and research as participative, open, and
      quality enhancing. To demonstrate the transformation of knowledge in practice,
      the authors present findings from a qualitative research study guided by the
      nursing theory called human becoming. The purpose of the study was to enhance
      understanding of quality of life for patients receiving acute psychiatric care. A
      descriptive exploratory design was used to guide data gathering and analysis of
      24 people. Findings are presented in themes that represent quality-of-life
      issues, including feelings of loss and shifting value priorities, the complex
      nature of relationships that ease and upset, and the hopes that fuel the intense
      struggle to go on living. Directions for practice and research are suggested.

PMID- 9633327
TI  - Analysis and synthesis of the role of the advanced practice nurse.
AB  - This is an exciting and challenging period for healthcare in our country. Many
      changes have already occurred within our system, and many more are on the
      horizon. As our system evolves, current nursing and healthcare literature
      describe the present and future needs of patients and communities, as well as how
      nurse practitioners (NPs) are playing an increasingly important role in providing
      health services in the United States. This role of the advanced practice nurse
      (APN), particularly the NP, is examined philosophically and in the context of
      changing healthcare needs and policies.

PMID- 9633328
TI  - Aesthetic research: sculpture.

PMID- 9633329
TI  - Clinical nurse specialist versatility is a key to opportunity.

PMID- 9633330
TI  - CNS role in women's health promotion and maintenance in a collaborative practice.
AB  - The clinical nurse specialist (CNS) has an instrumental role in health promotion
      and maintenance for women. In the obstetrical/gynecological private practice
      setting, working in collaboration with a physician and other healthcare
      providers, the CNS has the opportunity to exercise the subroles of clinician,
      educator, consultant, and researcher. The CNS, as primary caregiver, can be
      influential in meeting the guidelines of Healthy People 2000 and implementing the
      interventions suggested in the Guide to Clinical Preventative Services for women.

PMID- 9633331
TI  - Expert witness/legal consultant: the importance of data collection.
AB  - Claims resulting from medical negligence are increasing at an alarming rate,
      resulting in an increasing demand for nursing specialists who can act as a legal
      consultant or expert witness. This article reviews the role of the nurse as a
      legal consult and/or expert witness, emphasizes the importance of data
      collection, and offers a list of healthcare-related documents, records,
      materials, and other evidence to assist the consultant.

PMID- 9633332
TI  - Nurse-physician partnerships.

PMID- 9633333
TI  - Outcomes assessment of total hip and total knee arthroplasty: critical pathways,
      variance analysis, and continuous quality improvement.
AB  - Using critical pathways, with variance analysis and continuous quality
      improvement techniques to refine the pathways, the efficiency of total hip and
      total knee surgeries in one academic health center was maximized. Using a
      retrospective cohort study design, complications, readmissions,
      morbidity/mortality, and function scores were examined in two groups of patients
      attended by the same surgeon for the year before and the year after the
      implementation of an outcomes management program. The length of stay was reduced
      by 57% for knee patients and by 46% for hip patients. Hospital costs were reduced
      11% for all knees and 38% for hips. Complications were also significantly
      reduced. There was no statistically significant difference between pre- or
      postoperative knee or hip outcome scores. The program resulted in significant
      savings without adversely affecting overall outcome.

PMID- 9633334
TI  - Giving children our best efforts.

PMID- 9633335
TI  - Pain assessment in children with cognitive impairment. An exploration of self
      report skills.
AB  - Prior to surgery, 47 children (ages 8 to 17) with borderline to profound
      cognitive impairment were administered tasks to evaluate their understanding of
      the concepts of magnitude and ordinal position and their abilities to use a 0 to
      5 numerical scale to rate pain levels in schematic faces. Of the 111 children
      (ages 4 to 14) without cognitive impairment, were administered the same tasks.
      Nurses conducting preoperative evaluations predicted whether children would
      understand the numerical scale. Fifty percent (n = 3) of children with borderline
      and 35% (n = 7) of children with mild cognitive impairment (and all children 8
      years and older nonimpaired) correctly used the scale. Half of the children with
      cognitive impairment demonstrated skills (magnitude and ordinal position) that
      may allow them to use simpler pain rating methods. Nurses overestimated the
      abilities of cognitively impaired children (and younger children without
      cognitive impairment) to use the rating scale.

PMID- 9633336
TI  - Nurses' descriptions of caring for culturally diverse clients.
AB  - The nursing profession has responded to today's cultural diversity through theory
      development, association statements, research, and inclusion of cultural content
      in nursing curricula. This qualitative study was completed to explore whether
      this increased attention to cultural diversity is resulting in culturally
      sensitive nursing care. In this preliminary description of cross-cultural care,
      eight recently graduated nurses were each interviewed twice. Caring for
      culturally diverse clients is reflected by these participants as complex and
      challenging, due to the interrelatedness of multiple personal and contextual
      factors. Nurses' commitment to caring for culturally diverse clients varies,
      ranging from "resistant" to "generalist" to "impassioned." Contextual factors
      include the setting of health care, the support of colleagues, the institutional
      climate, the foundation of education, and the presence of racism. Despite the
      nursing profession's attention directed toward issues of cultural diversity, it
      seems that the goal of culturally sensitive care remains a distant ideal.

PMID- 9633337
TI  - Predictors of referral to cardiac rehabilitation and cardiac exercise self
      efficacy.
AB  - Cardiac rehabilitation (CR) has known benefits after myocardial infarction (MI)
      or coronary artery bypass surgery (CABG). Yet, only a small percentage of
      patients are referred for outpatient CR after hospital discharge. This study
      investigates patient characteristics related to referral to CR and cardiac
      exercise self-efficacy, a salient predictor of health behavior change and
      maintenance. Two hundred nineteen patients enrolled in the study. Of the 185
      patients who were CR candidates, 74 were referred to CR. Logistic regression
      analysis was used to identify variables related to CR referral. Results indicate
      that patient characteristics of having had fewer MIs or CABGs, having attended CR
      in the past, and being less physically active during leisure time are related to
      an increased likelihood of being referred to CR. Multiple regression analysis
      indicates that leisure physical activity is a predictor of cardiac exercise self
      efficacy. Implications for nurses who recruit patients for CR are discussed.

PMID- 9633338
TI  - Patients' explanatory models for heart failure and COPD exacerbations.
AB  - Although there is extensive information on the disease aspect of heart failure
      (HF) and chronic obstructive pulmonary disease (COPD), the illness aspect of
      these diseases has received limited attention. This limitation in our knowledge
      is of concern because these diseases are increasing in incidence and prevalence
      and contributing to the premature morbidity and mortality of thousands of
      persons. This naturalistic inquiry study was undertaken to describe the
      explanatory models (EMs) of persons hospitalized for HF (n = 30) or COPD (n = 30)
      exacerbations. In semistructured interviews, participants offered descriptions of
      the etiology, cause, and effects of their disease exacerbations and identified
      interventions that they believed would have helped prevent their hospitalizations
      or helped them to live better at home. The findings provide a basis for
      understanding the EMs of persons with HF or COPD as an initial step in making
      health care more relevant.

PMID- 9633339
TI  - Probable reasons for expressed agitation in persons with dementia.
AB  - Nursing home patients with dementia were videotaped in three previous studies.
      Sixty sequences of nine patients exhibiting agitated behaviors were examined to
      identify the most probable antecedents to agitation. Probable reasons were
      interpreted and applied to the Progressively Lowered Stress Threshold model,
      which suggests that agitation is stress related. Analysis suggests that agitation
      often serves as a form of communication. Two underlying reasons seem to be that
      the patient had loss of control over the situation and deficient autonomy. The
      most common causes for expressed agitation were interpreted as discomfort, a wish
      to be served immediately, conflict between patients or with nursing staff,
      reactions to environmental noises or sound, and invasion of personal space. It is
      recommended that nursing staff promote autonomy and independency for this group
      of patients whenever possible. By evaluating probable reasons for expressed
      agitation, the nursing staff can take steps to prevent or alleviate agitation.

PMID- 9633340
TI  - Preventing pressure sores in oncology patients.
AB  - This project addresses staff nurses' concerns about the development of hospital
      acquired pressure sores in cancer patients. The Braden Scale and the National
      Pressure Sore Advisory Panel Staging System were pilot tested. The incidence of
      hospital-acquired pressure sores was 8% and a mean Braden score of 16 was
      sufficiently sensitive (82%) and specific (84%) for use with our patient
      population. Eighty-two percent (9/11) of the patients with a score of 16 on the
      Braden Scale developed a pressure sore that day. The model of pressure sore
      development constructed by Braden and Bergstrom (1987) was used to guide the
      development of a pressure sore prevention protocol. The pilot test of this
      protocol over 6 months showed no decline in the incidence of hospital-acquired
      pressure sores and a reduction in the sensitivity and specificity of the Braden
      Scale. Possible explanations for this finding and revisions to the protocol are
      suggested.

PMID- 9633341
TI  - Patients at risk for atrial dysrhythmias after coronary bypass grafting.
AB  - Coronary artery bypass grafting (CABG) is widely used to treat patients with
      coronary artery disease. The most common complication after CABG is cardiac
      atrial dysrhythmias. Definitive patient characteristics that predict the
      development of atrial dysrhythmias postoperatively have not been identified. The
      authors review past research studies regarding predictors of atrial dysrhythmias
      and present research-based recommendations for clinical practice.

PMID- 9633342
TI  - End-tidal carbon dioxide monitoring for weaning patients: a pilot study.
AB  - This research pilot study evaluates the usefulness of capnography for patients
      being weaned from mechanical ventilation in a medical intensive care unit (MICU).
      The hypothesis that capnography would allow for more rapid weaning from
      mechanical ventilation, and require fewer arterial blood gases (ABGs) during the
      process, was found to be untrue. Several implications for critical care nursing
      practices were derived from the literature review and findings of this study.

PMID- 9633343
TI  - Fulminant hepatic failure in acute acetaminophen overdose.
AB  - Fulminant hepatic failure is a serious complication of acetaminophen overdose.
      The cascade of complications starts with an alert patient that can quickly result
      in hepatic coma and even death. The nurse completes a poisoning history, provides
      an antidote, and assesses the extent of hepatic failure from an overdose. This
      article uses a case study to describe the problems and nursing care for the
      patient with hepatic failure from acetaminophen overdose. Advanced assessment
      skills by the critical care nurse enable prompt recognition of postoverdose
      complications for early intervention and treatment. Acute care nurse
      practitioners, utilizing the same techniques, can develop protocols for emergency
      or intensive care units where these patients may be admitted and subsequently
      cared for.

PMID- 9633344
TI  - We have a beautiful ICU!

PMID- 9633345
TI  - Intrahospital transport of the critically ill adult: a research review and
      implications.
AB  - Transporting the critically ill adult from the relative stability of the critical
      care environment to a testing site or new area is a nursing responsibility. Yet
      current research about the risks and benefits of intrahospital transport is at
      times conflicting. This article provides an analysis of available research on the
      critical elements involved in intrahospital transport and suggests
      recommendations for clinical practice.

PMID- 9633346
TI  - Health needs of coronary artery bypass graft surgery patients at discharge.
AB  - Shortened hospital stays could potentially lead to unmet patient needs. This
      descriptive study utilizes critical pathway data and the Omaha System to identify
      the health needs of coronary artery bypass surgery patients at time of discharge.
      The most common health needs were education, sleep/rest and rehabilitation.
      Nursing implications relating to these health needs are also identified.

PMID- 9633347
TI  - [The long way to the breast--preparations for nursing a premature needing
      intensive care].

PMID- 9633348
TI  - [Care of the sedated child].

PMID- 9633349
TI  - [Prevention and health promotion in future young families].

PMID- 9633350
TI  - [The adolescent in a pediatric hospital--special measures in his care].

PMID- 9633351
TI  - [Basic stimulation--further education for nursing students].

PMID- 9633352
TI  - [Parents in the pediatric hospital. Description of the real situation from the
      viewpoint of Germany's pediatric nurses].

PMID- 9633353
TI  - [Parents in the pediatric hospital. Description of the real situation from the
      viewpoint of the Action Committee "Child in the Hospital", Federal Association].

PMID- 9633354
TI  - [Parents in the pediatric hospital. Description of the real situation from the
      viewpoint of the Austrian pediatric nurses].

PMID- 9633355
TI  - [Project "Care of Parents"].

PMID- 9633356
TI  - [Special infectious disease unit for the treatment of tuberculosis].

PMID- 9633357
TI  - [Toxic and less toxic plants. 37].

PMID- 9633358
TI  - [Creativity in nursing. Original solutions are needed].

PMID- 9633359
TI  - [Caring for patients who threaten suicide. The relationship as a bridge to life].

PMID- 9633360
TI  - [Nursing in Russia. Hope for a broken country].

PMID- 9633361
TI  - [Nurses in emergency work. Staying hunger, saving lives].

PMID- 9633362
TI  - [Nurses working during peace. A sharp look at Western medicine].

PMID- 9633363
TI  - [Verena Fiechter, the first white "Queen Mother"].

PMID- 9633364
TI  - [New attempts at financing. A holistic view of diseases].

PMID- 9633365
TI  - [When there is nothing more to say...].

PMID- 9633366
TI  - [A humorous account. Head nurse in a nursing home. A symphonic day].

PMID- 9633367
TI  - [Reflections on the therapeutic relationship. Who will be the patient of
      tomorrow?].

PMID- 9633368
TI  - [The systemic approach 2. Concrete applications].

PMID- 9633369
TI  - [Art and voice. The expression of inner beauty].

PMID- 9633370
TI  - Midwifery in the Rainbow Nation of South Africa.

PMID- 9633371
TI  - Recent immigration and the misery of motherhood: a discussion of pertinent
      issues.
AB  - In this paper it is assumed that the high rates of misery experienced by most new
      mothers in contemporary Western society are socially and culturally induced.
      Women from non-English-speaking backgrounds (NESB) recuperate from the stress of
      birth, often further complicated by morbidity from intervention, frequently alone
      and without practical household help. They often embark on their new mothering
      role with little support or guidance. In a Western society which markets a
      romanticized Anglo image of motherhood, where happy, contented, smiling babies
      and glamorous mothers appear as the norm, it is not surprising that women from
      NESB find becoming a mother in Australia difficult. Their difficulties are
      exacerbated as they frequently come from cultures where women are nurtured,
      valued and supported at this time in their lives. These women are often socially
      isolated in their new country, within an alien health system and separated from
      their normal birth and postpartum practices. Their misery can only be imagined,
      as mostly it is hidden and suffered alone. Providing a diagnosis of depression in
      women who are unhappy, but not clinically depressed, is likely to be even less
      helpful and more damaging for NESB women than for Anglo-Australian women. A
      diagnosis of depression excuses Western society for accepting responsibility for
      alleviating the isolation of new mothers by labelling them as 'sick'.

PMID- 9633372
TI  - Fathers' experiences of childbirth.
AB  - OBJECTIVE: To describe how fathers who are present during childbirth experience
      the event, what they feel during childbirth and how they understand the meaning
      of childbirth. DESIGN: Survey using questionnaire. SETTING: Maternity unit in
      Finland. PARTICIPANTS: A non-random sample of fathers (n = 137) who were present
      at the birth of their baby at one university hospital in Finland. The response
      rate was 81% (n = 107). MEASUREMENTS AND FINDINGS: Young fathers and those
      expecting their first baby reported feeling uncomfortable during delivery more
      frequently than others. Almost all said that they had plenty of good experiences,
      younger fathers more so than older fathers. The fathers expressed their
      confidence in the staff and described the environment at the hospital as
      pleasant. They said their presence at delivery was important for their growth
      into fatherhood. The best experience was the moment that the baby entered the
      world. The hardest things were the pain experienced by their partner and being
      unable to help. Most of the fathers were very pleased with current midwifery
      practices followed in childbirth, however, it was felt that more attention ought
      to be paid to pain relief and to supporting and providing guidance to the father
      during delivery. IMPLICATIONS FOR PRACTICE: The work of midwives should be
      planned so that fathers can feel secure and comfortable. Further studies are
      needed into the ability of midwives to support fathers in their fatherhood.

PMID- 9633373
TI  - Education for clinical decision making in midwifery practice.
AB  - OBJECTIVE: To present an approach to developing clinical decision-making skills
      in midwifery students. DESCRIPTION: Use of simulations, 'thinking aloud'
      technique, reflection and the decision rules of experienced midwives are proposed
      for developing clinical-reasoning skills and acquiring skilled clinical
      knowledge. IMPLICATIONS: Educators are encouraged to recognise that skill
      acquisition in clinical decision making requires practise before students engage
      fully in the clinical setting. The process of decision making is emphasised as
      essential for students to experience so they develop an understanding of the
      clinical information attended to, the sequence in which the information is
      processed and the rules used to combine information to reach clinical judgements.
      By using clinical simulations developed from 'real cases' the process of decision
      making is able to be experienced by students. Further, if these simulations are
      accompanied by the collection of verbal protocols, students have opportunities to
      retrospectively explore their decision making with reflection. In addition, the
      presentation and use of decision rules of experienced midwives has the potential
      to enhance the development of skills in students.

PMID- 9633374
TI  - A phenomenological study of women's experiences of complicated childbirth.
AB  - OBJECTIVE: To describe women's experiences of a complicated childbirth. DESIGN: A
      qualitative study using a phenomenological approach. Data were collected by tape
      recorded interviews. SETTING: Sahlgrenska University Hospital, Goteborg, Sweden
      in 1995. PARTICIPANTS: 10 women, eight primiparous and two multiparous, who were
      interviewed two to five days post delivery. KEY FINDINGS: The essential meaning
      of women's experiences of complicated childbirth is the desire to be recognised
      and affirmed as a genuine subject. If this happens they feel accepted as
      childbearing women and as mothers-to-be, even if obstetric interventions are
      necessary and high technology is used. IMPLICATIONS FOR PRACTICE: By
      understanding and respecting every women as an individual the caregivers support
      women giving birth and make them feel accepted, thus paving the way for them to
      gain control over the situation. Through a true dialogue resulting in a trustful
      relationship, the women can manage even emergency situations. Separation of the
      mother and her baby should be avoided if possible.

PMID- 9633375
TI  - Staying in control: women's experiences of labour in water.
AB  - AIM: To examine women's attempts at control during labour in water. DESIGN: An
      exploratory design consisting of tape-recorded, in-depth interviews using the
      grounded theory approach. SETTING: A medium sized town in the south of England.
      The data were collected in the maternity unit of a local general hospital set in
      a semi-rural location. PARTICIPANTS: Nine women who had chosen to spend their
      labour process in water. The participants selected had experienced a normal
      pregnancy and given birth to a healthy baby at term. FINDINGS: Labour in water
      was seen by all but one of the participants as beneficial, particularly as they
      felt that this gave them more control over the process. They valued their own
      involvement in determining the outcome of their care. The support of the midwife
      in making decisions was seen as necessary to remain in control. CONCLUSIONS:
      Labour in water was a positive experience for this group of healthy women. The
      feeling of freedom to make decisions, however, was balanced with a wish for the
      support of the midwife.

PMID- 9633376
TI  - A comparison of the incidence of breast feeding two and four months after
      delivery in mothers discharged within 72 hours and after 72 hours post delivery.
AB  - OBJECTIVE: To compare breast feeding at two and four months after delivery in
      mothers discharged early (ED = before 72 hours post delivery) and late (LD =
      after 72 hours post delivery), and to explore the factors of greatest importance
      to the successful practice of breast feeding. DESIGN: Ex-post facto design.
      SETTING: In the country of Harryda, Sweden. PARTICIPANTS: All Swedish speaking
      women in the country of Harryda whose babies were born between 01.01.94 and
      31.05.94 and who were registered at the Child Health Station (CHS) by the age of
      three months. One hundred and ninety women were invited to participate and 157
      (83%) accepted. MEASUREMENTS AND FINDINGS: No significant difference was found in
      the breast feeding rates between the ED and LD group. However, ED mothers breast
      fed exclusively to a higher extent at two and at four months (exclusive breast
      feeding: at two months 89% and 86% respectively, and at four months 84% and 74%
      respectively, partial breast feeding: at two months 6% and 10% respectively, and
      at four months 5% and 12% respectively). If the woman considered that she had
      received encouragement and support while breast feeding for the first time, the
      probability of her breast feeding at two and at four months were about six times
      as great (Exp(B) 5.7594, df = 1, p = 0.0270; (Exp(B) 5.9781 df = 1, p = 0.0005
      respectively). KEY CONCLUSIONS: The length of the hospital stay had no
      significant effect on the incidence of breast feeding at two and four months post
      delivery. The most predominant factors influencing breast feeding were seen to be
      the mother's first experience of breast feeding and the degree of support, help
      and encouragement she received. Less than half of the women received a visit from
      the CHS nurse after their return home from hospital. IMPLICATIONS FOR PRACTICE:
      The findings suggest that it is important that the midwife or nurse should
      prepare, support and encourage the mother when breast feeding for the first time.
      The midwife's or nurse's interventions are important for the incidence of breast
      feeding, at least during the first four months, and indirectly affect public
      health. This must also be taken into consideration when caring for mothers in the
      delivery ward and before discharge, i.e. that the breast feeding is working well,
      that the mother experiences it as working well, and also for planning follow-up
      after discharge.

PMID- 9633377
TI  - Women's perceptions of maternity carers.
AB  - OBJECTIVE: To investigate women's perceptions about the roles of different types
      of staff providing maternity care. DESIGN: A descriptive study using screening
      questionnaires and semi-structured interviews. SETTING: Two hospitals in the
      north of England, one in a predominantly urban, inner-city area and the other in
      a mixed urban-rural area. PARTICIPANTS: 537 women between 16 and 24 weeks'
      gestation from two hospitals serving urban and rural areas completed screen
      questionnaires, and 247 (46%) were interviewed in their homes. In this paper we
      report on the findings of the interview study. FINDINGS: The majority of women
      were clear about the role of the midwife in the maternity care of all women.
      Obstetricians were primarily perceived as being there to provide specialist or
      emergency care. Many women were uncertain about the specific role of their GP in
      maternity care. There was variation in women's views about whether different
      types of staff are qualified to perform particular tasks. IMPLICATIONS FOR
      PRACTICE: Women need information about the roles and functions of maternity
      carers in order to make choices about their care.

PMID- 9633378
TI  - A survey of information given during pregnancy by midwives to parents about
      neonatal unit care, whether or not the baby was likely to require such care.
AB  - OBJECTIVE: To determine what information is given by midwives to parents in
      Scotland about care in a neonatal unit (a designated nursery offering special
      and/or intensive care to preterm and sick/vulnerable newborn babies), whether or
      not the baby is expected to require such care. DESIGN: A survey using self
      completion questionnaires. SETTING: The questionnaires were sent to identified
      senior midwives in community and hospital settings in Scotland. PARTICIPANTS: 155
      midwives, including 100 midwives involved in preparation for parenthood classes,
      21 midwives responsible for hospital-based antenatal care, 17 midwives
      responsible for care in labour wards and 17 midwives responsible for care in
      neonatal units. FINDINGS: Information about care in a neonatal unit was offered
      by all groups surveyed to all parents with whom the midwives were in contact.
      Eight rural community midwives did not routinely give information. Midwives
      involved in preparation for parenthood classes offered specific information at a
      median gestation of 28 weeks. The midwives addressed most suggested topics. The
      most commonly included topics were why babies require neonatal care and what
      problems they may have. The least commonly included topic was the long-term
      problems the baby may have. Several methods of teaching were used, especially
      discussion and question and answer, with a visit to the neonatal unit a common
      strategy. Few midwives shared information using audio-visual methods. KEY
      CONCLUSIONS: The majority of midwives sampled offered information prenatally
      about neonatal unit care, with many tailoring this to the womanis needs.
      IMPLICATIONS FOR PRACTICE: There should be consideration of the need to give
      information to all pregnant women and their partners, the most appropriate time
      for giving such information and the use of audio-visual teaching resources. The
      findings will inform further study of the extent to which such information meets
      the needs of parents.

PMID- 9633379
TI  - Potential influence in shaping nursing is incredibly important.

PMID- 9633380
TI  - Not so sweet charity.

PMID- 9633383
TI  - Inside health.

PMID- 9633381
TI  - Posing a threat.

PMID- 9633382
TI  - Academic bandwagon.

PMID- 9633384
TI  - A nurse's nurse.

PMID- 9633385
TI  - Lessons for sexual health.

PMID- 9633386
TI  - A disease of today.

PMID- 9633387
TI  - Local learning.

PMID- 9633388
TI  - Psoriasis in general practice.
AB  - This report, based on a resource pack for primary care nurses, describes the
      features of psoriasis and reviews current prevention and treatments. The pack
      emphasises the important role of nurses in helping people to maintain their
      confidence and independence in the face of this chronic disease.

PMID- 9633389
TI  - Care pathways development and implementation.
AB  - Care pathways are increasingly being used in the UK as a tool for managing
      clinical processes and patient outcomes. This article describes some of the key
      elements of care pathways, highlights factors in successful implementation and
      discusses some concerns about their use.

PMID- 9633390
TI  - Promoting the role of ward sisters and charge nurses.
AB  - Ward sisters and charge nurses face new and different pressures in a changing
      health service. This year's RCN Congress will call for a national development
      programme for ward managers. Here, the authors describe how, using a 'think
      tank', workshops and a seminar, one trust identified the obstacles to good
      nursing practice and developed positive ways of overcoming them.

PMID- 9633391
TI  - Marketing a health visiting service.
AB  - This year's RCN Congress will debate the importance of retaining health visiting
      as a service available to all. On the basis of her analysis of recent
      professional and political events, this author predicts the likely capacity of
      health visiting to market its universal approach to population health.

PMID- 9633392
TI  - Numeracy skills.
AB  - This article describes how to solve some of the more frequently encountered
      mathematical problems experienced in clinical practice. It covers equations,
      dosage calculations, and ratios and percentages, as well as touching on the use
      of graphs and conversion tables.

PMID- 9633393
TI  - Setting the agenda.

PMID- 9633394
TI  - Debating society.

PMID- 9633395
TI  - A solid base.

PMID- 9633396
TI  - Sexual debate.

PMID- 9633397
TI  - A change of climate.

PMID- 9633398
TI  - Tell the world.

PMID- 9633400
TI  - Expert advice.

PMID- 9633399
TI  - Case study.

PMID- 9633401
TI  - You have a right to object to abortion, but not to impose your views on others.

PMID- 9633402
TI  - Failing the screen test.

PMID- 9633403
TI  - Margaret Howard has spent her life nursing others, but when she got cancer the
      NHS failed her.

PMID- 9633404
TI  - A joint effort.